PMID- 25044727
TI  - Rationalization of an unusual solvent-induced inversion of enantiomeric excess in
      organocatalytic selenylation of aldehydes.
AB  - An unusual solvent-induced inversion of the sense of enantioselectivity observed
      in the alpha-selenylation of aldehydes catalyzed by a diphenylprolinol silyl
      ether catalyst is correlated to the presence of intermediates formed subsequent
      to the highly selective C-Se bond-forming step in the catalytic cycle. This work
      provides support for a mechanistic concept for enamine catalysis and includes a
      general role for "downstream intermediates" in selectivity outcomes in
      organocatalysis.

PMID- 25044728
TI  - Maize growing duration was prolonged across China in the past three decades under
      the combined effects of temperature, agronomic management, and cultivar shift.
AB  - Maize phenology observations at 112 national agro-meteorological experiment
      stations across China spanning the years 1981-2009 were used to investigate the
      spatiotemporal changes of maize phenology, as well as the relations to
      temperature change and cultivar shift. The greater scope of the dataset allows us
      to estimate the effects of temperature change and cultivar shift on maize
      phenology more precisely. We found that maize sowing date advanced significantly
      at 26.0% of stations mainly for spring maize in northwestern, southwestern and
      northeastern China, although delayed significantly at 8.0% of stations mainly in
      northeastern China and the North China Plain (NCP). Maize maturity date delayed
      significantly at 36.6% of stations mainly in the northeastern China and the NCP.
      As a result, duration of maize whole growing period (GPw) was prolonged
      significantly at 41.1% of stations, although mean temperature (Tmean) during GPw
      increased at 72.3% of stations, significantly at 19.6% of stations, and Tmean was
      negatively correlated with the duration of GPw at 92.9% of stations and
      significantly at 42.9% of stations. Once disentangling the effects of temperature
      change and cultivar shift with an approach based on accumulated thermal
      development unit, we found that increase in temperature advanced heading date and
      maturity date and reduced the duration of GPw at 81.3%, 82.1% and 83.9% of
      stations on average by 3.2, 6.0 and 3.5 days/decade, respectively. By contrast,
      cultivar shift delayed heading date and maturity date and prolonged the duration
      of GPw at 75.0%, 94.6% and 92.9% of stations on average by 1.5, 6.5 and 6.5
      days/decade, respectively. Our results suggest that maize production is adapting
      to ongoing climate change by shift of sowing date and adoption of cultivars with
      longer growing period. The spatiotemporal changes of maize phenology presented
      here can further guide the development of adaptation options for maize production
      in near future. 

PMID- 25044726
TI  - Oxytocin levels are lower in premenopausal women with type 1 diabetes mellitus
      compared with matched controls.
AB  - BACKGROUND: Oxytocin, a hormone most commonly associated with parturition and
      lactation, may have additional roles in diabetes complications. We determined
      oxytocin levels in premenopausal women with type 1 diabetes mellitus (T1DM)
      compared with non-diabetic controls and examined associations of oxytocin with
      health behaviours, clinical factors, biomarkers, kidney function and bone health.
      Lower oxytocin was hypothesized for T1DM. METHODS: A cross-sectional study of
      premenopausal women with T1DM (n = 88) from the Wisconsin Diabetes Registry
      Study, a population-based cohort of incident T1DM cases, and matched non-diabetic
      controls (n = 74) was conducted. RESULTS: Women with T1DM had lower oxytocin
      levels than controls adjusting for caffeine and alcohol use (p = 0.03). Health
      behaviours associated with oxytocin differed between women with and without T1DM:
      oxytocin was negatively associated with hormonal contraceptive use (quantified as
      lifetime contraceptive oestrogen exposure) in women with T1DM (p = 0.003),
      whereas positively related to hormonal contraceptive use (quantified as
      never/former/current) in controls (p < 0.001). Oxytocin had a positive
      association with adiposity (waist-to-hip ratio and leptin) in women with T1DM and
      a negative relationship with adiposity (weight gain) in controls. In T1DM only,
      oxytocin was positively associated with caffeine intake (p = 0.01) and negatively
      associated with alcohol use (p = 0.01). Oxytocin was not related to glycemic
      control, kidney function or bone health in T1DM. CONCLUSIONS: Oxytocin levels are
      lower in women with T1DM than matched controls. Oxytocin also has opposing
      associations with hormonal contraceptives and adiposity in women with and without
      T1DM. Research is needed to determine if the altered oxytocin milieu in T1DM is
      associated with oxytocinher health outcomes.

PMID- 25044729
TI  - Medical management of allergic fungal rhinosinusitis following endoscopic sinus
      surgery: an evidence-based review and recommendations.
AB  - BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a subset of polypoid chronic
      rhinosinusitis that is characterized by the presence of eosinophilic mucin with
      fungal hyphae within the sinuses and a Type I hypersensitivity to fungi. The
      treatment of AFRS usually involves surgery in combination with medical therapies
      to keep the disease in a dormant state. However, what constitutes an optimal
      medical regimen is still controversial. Hence, the purpose of this article is to
      provide an evidence-based approach for the medical management of AFRS. METHODS: A
      systemic review of the literature on the medical management of AFRS was performed
      using Medline, EMBASE, and Cochrane Review Databases up to March 15, 2013. The
      inclusion criteria were as follows: patients >18 years old; AFRS as defined by
      Bent and Kuhn; post-sinus surgery; studies with a clearly defined end point to
      evaluate the effectiveness of medical therapy in postoperative AFRS patients.
      RESULTS: This review identified and assessed 6 medical modalities for AFRS in the
      literature: oral steroids; topical steroids; oral antifungals; topical
      antifungals; immunotherapy; and leukotriene modulators. CONCLUSION: Based on
      available evidence in the literature, postoperative systemic and standard topical
      nasal steroids are recommended in the medical management of AFRS. Nonstandard
      topical nasal steroids, oral antifungals, and immunotherapy are options in cases
      of refractory AFRS. No recommendations can be provided for topical antifungals
      and leukotriene modulators due to insufficient clinical research reported in the
      literature.

PMID- 25044730
TI  - Production, HPLC analysis, and in situ apoptotic activities of swainsonine toward
      lepidopteran, Sf-21 cell line.
AB  - Swainsonine, a secondary metabolite from Metarhizium anisopliae has been
      extensively studied in the complementary areas of therapeutics and toxicology.
      This work aims to develop a simple UV-HPLC method of analyses for swainsonine in
      Metarhizium fermentation broth and to explore its in situ entomotoxic activities.
      The partially purified broth was quantitatively analyzed using middle UV (205 nm)
      reverse phase HPLC method with different mobile phases and gradient programmes.
      Swainsonine was eluted as single peak at (te ) 6.0-6.9 min with average
      concentration of 4.04 +/- 0.52 MUg/mL using optimal mobile phase (0.1%
      trifluoroacetic acid in water and acetonitrile). The mass spectrometry analysis
      further indicated the characteristic MS1 species for swainsonine, [M+H](+) 174.30
      in corresponding HPLC peaks. The antiproliferative effects of swainsonine on
      lepidopteran, Sf-21 cells were determined through 3-(4, 5-dimethylthia-zol-2-yl)
      2, 5-diphenyl tetrazolium bromide (IC50 standard  = 3.90 MUM and IC50 purified  =
      5.27 MUM) and trypan blue dye exclusion (IC50 standard  = 6.91 MUM and IC50
      purified  = 8.67 MUM) assays. The fluorescence activated cell sorting evaluation
      of Sf-21 cells showed nearly 35% and 42% of population in various apoptotic
      stages at 36 h, when treated with standard and purified swainsonine,
      respectively. The morphodimensional field emission scanning electron and atomic
      force microscopic analyses further confirmed the characteristic apoptotic
      features like membrane blebbings, ruptures and volume shrinkage in the
      lepidopteran cells after 24-36 h of post-treatment incubation. The study
      describes the potential entomotoxic activities of swainsonine and its role in the
      virulence of Metarhizium spp.

PMID- 25044731
TI  - Characterization of missense alleles of the glial cells missing gene of
      Drosophila.
AB  - Glial cells missing (Gcm) is the primary regulator of glial cell fate in
      Drosophila. Gcm belongs to a small family of transcriptional regulators involved
      in fundamental developmental processes found in diverse animal phyla including
      vertebrates. Gcm proteins contain the highly conserved DNA-binding GCM domain,
      which recognizes an octamer DNA sequence. To date, studies in Drosophila have
      primarily relied on gcm alleles caused by P-element induced DNA deletions at the
      gcm locus, as well as a null allele caused by a single base pair substitution in
      the GCM domain that completely abolishes DNA binding. Here I characterize two
      hypomorphic missense alleles of gcm with intermediate glial cells missing
      phenotypes. In embryos homozygous for either of these gcm alleles the number of
      glial cells in the central nervous cystem (CNS) is reduced approximately in half.
      Both alleles have single amino acid changes in the GCM domain. These results
      suggest that Gcm protein activities in these mutant alleles have been attenuated
      such that they are operating at threshold levels, and trigger glial cell
      differentiation in neural precursors in the CNS in a stochastic fashion. These
      hypomorphic alleles provide additional genetic resources for understanding Gcm
      functions and structure in Drosophila and other species.

PMID- 25044732
TI  - Raman spectroscopy of serum: A study on 'pre' and 'post' breast adenocarcinoma
      resection in rat models.
AB  - Risk of recurrence is a major problem in breast cancer management. Currently
      available prognostic markers have several disadvantages including low sensitivity
      and specificity, highlighting the need for new prognostic techniques. One of the
      candidate techniques is serum-based Raman spectroscopy (RS). In this study,
      feasibility of using RS to distinguish 'pre' from 'post' breast tumor resection
      serum in rats was explored. Spectral analysis suggests change in proteins and
      amino acid profiles in 'post' compared to 'pre-surgical' group. Principal
      Component-Linear-Discriminant-Analysis shows 87% and 91% classification
      efficiency for 'pre' and 'post-surgical' groups respectively. Thus, the study
      further supports efficacy of RS for theranostic applications. 

PMID- 25044733
TI  - Reduced structural connectivity within a prefrontal-motor-subcortical network in
      amyotrophic lateral sclerosis.
AB  - BACKGROUND: To investigate white matter structural connectivity changes
      associated with amyotrophic lateral sclerosis (ALS) using network analysis and
      compare the results with those obtained using standard voxel-based methods,
      specifically Tract-based Spatial Statistics (TBSS). METHODS: MRI data were
      acquired from 30 patients with ALS and 30 age-matched healthy controls. For each
      subject, 85 grey matter regions (network nodes) were identified from high
      resolution structural MRI, and network connections formed from the white matter
      tracts generated by diffusion MRI and probabilistic tractography. Whole-brain
      networks were constructed using strong constraints on anatomical plausibility and
      a weighting reflecting tract-averaged fractional anisotropy (FA). RESULTS:
      Analysis using Network-based Statistics (NBS), without a priori selected regions,
      identified an impaired motor-frontal-subcortical subnetwork (10 nodes and 12
      bidirectional connections), consistent with upper motor neuron pathology, in the
      ALS group compared with the controls (P = 0.020). Reduced FA in three of the
      impaired network connections, which involved fibers of the corticospinal tract,
      correlated with rate of disease progression (P <= 0.024). A novel network-tract
      comparison revealed that the connections involved in the affected network had a
      strong correspondence (mean overlap of 86.2%) with white matter tracts identified
      as having reduced FA compared with the control group using TBSS. CONCLUSION:
      These findings suggest that white matter degeneration in ALS is strongly linked
      to the motor cortex, and that impaired structural networks identified using NBS
      have a strong correspondence to affected white matter tracts identified using
      more conventional voxel-based methods.

PMID- 25044734
TI  - Iron(III) catecholates for cellular imaging and photocytotoxicity in red light.
AB  - Iron(III) complexes [Fe(L)(L')(NO3)]--in which L is phenyl-N,N-bis[(pyridin-2
      yl)methyl]methanamine (1), (anthracen-9-yl)-N,N-bis[(pyridin-2
      yl)methyl]methanamine (2), (pyreny-1-yl)-N,N-bis[(pyridin-2-yl)methyl]methanamine
      (3-5), and L' is catecholate (1-3), 4-tert-butyl catecholate (4), and 4-(2
      aminoethyl)-benzene-1,2-diolate (5)--were synthesized and their photocytotoxic
      properties examined. The five electron-paramagnetic complexes displayed a
      Fe(III)/Fe(II) redox couple near -0.4 V versus a saturated calomel electrode
      (SCE) in DMF/0.1 M tetrabutylammonium perchlorate (TBAP). They showed
      unprecedented photocytotoxicity in red light (600-720 nm) to give IC50~15 MUM in
      various cell lines by means of apoptosis to generate reactive oxygen species.
      They were ingested in the nucleus of HeLa and HaCaT cells in 4 h, thereby
      interacting favorably with calf thymus (ct)-DNA and photocleaving pUC19 DNA in
      red light of 785 nm to form hydroxyl radicals.

PMID- 25044735
TI  - The structure of a transient complex of a nonribosomal peptide synthetase and a
      cytochrome P450 monooxygenase.
AB  - Studying the interplay between nonribosomal peptide synthetases (NRPS), a major
      source of secondary metabolites, and crucial external modifying enzymes is a
      challenging task since the interactions involved are often transient in nature.
      By applying a range of synthetic inhibitor-type compounds, a stabilized complex
      appropriate for structural analysis was generated for such a tailoring enzyme and
      an NRPS domain. The complex studied comprises an NRPS peptidyl carrier protein
      (PCP) domain bound to the Cytochrome P450 enzyme that is crucial for the
      provision of beta-hydroxylated amino acid precursors in the biosynthesis of the
      cyclic depsipeptide skyllamycin. The structure reveals that complex formation is
      governed by hydrophobic interactions, the presence of which can be controlled
      through minor alterations in PCP structure that enable selectivity amongst
      multiple highly similar PCP domains. 

PMID- 25044736
TI  - Concerted asynchronous hula-twist photoisomerization in the S65T/H148D mutant of
      green fluorescent protein.
AB  - Fluorescence emission of wild-type green fluorescent protein (GFP) is lost in the
      S65T mutant, but partly recovered in the S65T/H148D double mutant. These
      experimental findings are rationalized by a combined quantum mechanics/molecular
      mechanics (QM/MM) study at the QM(CASPT2//CASSCF)/AMBER level. A barrierless
      excited-state proton transfer, which is exclusively driven by the Asp148 residue
      introduced in the double mutant, is responsible for the ultrafast formation of
      the anionic fluorescent state, which can be deactivated through a concerted
      asynchronous hula-twist photoisomerization. This causes the lower fluorescence
      quantum yield in S65T/H148D compared to wild-type GFP. Hydrogen out-of-plane
      motion plays an important role in the deactivation of the S65T/H148D fluorescent
      state. 

PMID- 25044737
TI  - Application of in operando UV/Vis spectroscopy in lithium-sulfur batteries.
AB  - Application of UV/Vis spectroscopy for the qualitative and quantitative
      determination of differences in the mechanism of lithium-sulfur battery behavior
      is presented. With the help of catholytes prepared from chemically synthesized
      stoichiometric mixtures of lithium and sulfur, calibration curves for two
      different types of electrolyte can be constructed. First-order derivatives of
      UV/Vis spectra show five typical derivative peak positions in both electrolytes.
      In operando measurements show a smooth change in the UV/Vis spectra in the
      wavelength region between lambda=650 and 400 nm. Derivatives are in agreement
      with derivative peak positions observed with catholytes. Recalculation of
      normalized reflections of UV/Vis spectra obtained in operando mode enable the
      formation of polysulfides and their concentrations to be followed. In such a way,
      it is possible to distinguish differences in the mechanism of polysulfide
      shuttling between two electrolytes and to correlate differences in capacity
      fading.

PMID- 25044738
TI  - Ethical decision-making in Internet research: another slant on the "Recursive
      Fury" debate.

PMID- 25044739
TI  - Dr. Jeffrey Bauer inducted as second honorary fellow of the American Association
      of Nurse Practitioners.

PMID- 25044740
TI  - Surviving a brain tumor in childhood: impact on family functioning in
      adolescence.
AB  - OBJECTIVE: To investigate family functioning in families with an adolescent
      survivor of a pediatric brain tumor. We explored whether adolescent, parent,
      disease and treatment factors, and demographic characteristics predicted family
      functioning. METHODS: In this cross-sectional study, 45 adolescent survivors of
      pediatric brain tumors and their parents completed self-report questionnaires on
      family functioning, and emotional and behavioral problems. Parents completed
      questionnaires on their own mental health and the burden of treatment. RESULTS:
      Compared to general population norms, adolescents reported higher levels of
      cohesion, expressiveness, organization, control, family values and social
      orientation, and absence of conflict. Parents reported higher levels of social
      orientation and lower levels of conflict and family values. The only predictor of
      family functioning was current age of the adolescent; older adolescents reported
      less family conflict. No relation was found between family functioning and
      emotional and behavioral problems, disease- or treatment factors, and demographic
      variables. CONCLUSIONS: In this exploratory study, adolescent survivors of a
      pediatric brain tumor characterized their families by higher levels of cohesion,
      expressiveness, organization, control, family values and social orientation, and
      absence of conflict, which differs from the more normative view held by their
      parents. A higher adolescent age predicted less family conflict, which may
      indicate deviant autonomy development in these survivors. Because of limitations
      of this study, conclusions should be considered provisional; they provide clues
      for further research in this area.

PMID- 25044741
TI  - Thoracic aortic aneurysm expansion due to late distal stent graft-induced new
      entry.
AB  - OBJECTIVES: This study analyzed the mechanism and risk factors of thoracic aortic
      aneurysm expansion due to late distal stent graft-induced new entry (dSINE).
      BACKGROUND: This late complication of thoracic endovascular aneurysm repair
      (TEVAR) for aortic dissection is under-recognized but potentially life
      threatening. METHODS: In 142 patients who underwent TEVAR with endovascular entry
      sealing for acute and chronic aortic type B dissection, using commercially
      available straight (nontapered) stent-grafts, we examined the oversizing rate,
      the aortic taper ratio, and the need for reintervention. RESULTS: Nine of 142
      patients developed thoracic aortic aneurysm expansion due to dSINE after TEVAR.
      The median follow-up was 47.5 +/- 37.4 months. There was a significant difference
      in the distal stent-aorta angle between the patients with and without dSINE
      (149.08 +/- 15.09 degrees  vs. 166.72 +/- 12.47 degrees , P < 0.005). Patients
      with dSINE showed a significantly higher taper ratio of the true lumen of the
      aorta (40.9 +/- 14.13% vs. 25.36 +/- 20.2%, P < 0.05). There was also a
      significant difference in the oversizing of the stent-graft in the distal landing
      zone (95.88 +/- 49.3% vs. 55.94 +/- 36.23%, P < 0.01). All patients with dSINE
      underwent a secondary endograft procedure without any complications or deaths. In
      7 cases we used a custom-made, highly tapered stent-graft. CONCLUSIONS: Lifelong
      follow-up of patients is mandatory after TEVAR. A stent-graft with a tapered
      design should be used in aortic dissection to avoid oversizing and devastating
      late complications.

PMID- 25044743
TI  - Significance of clinical and biologic features in Stage 3 neuroblastoma: a report
      from the International Neuroblastoma Risk Group project.
AB  - BACKGROUND: International Neuroblastoma Staging System (INSS) Stage 3
      neuroblastoma is a heterogeneous disease. Data from the International
      Neuroblastoma Risk Group (INRG) database were analyzed to define patient and
      tumor characteristics predictive of outcome. PROCEDURE: Of 8,800 patients in the
      INRG database, 1,483 with INSS Stage 3 neuroblastoma and complete follow-up data
      were analyzed. Secondary analysis was performed in 1,013 patients (68%) with MYCN
      non-amplified (NA) tumors. Significant prognostic factors were identified via log
      rank test comparisons of survival curves. Multivariable Cox proportional hazards
      regression model was used to identify factors independently predictive of event
      free survival (EFS). RESULTS: Age at diagnosis (P < 0.0001), tumor MYCN status (P
      < 0.0001), and poorly differentiating/undifferentiated histology (P = 0.03) were
      independent predictors of EFS. Compared to other Stage 3 subgroups, outcome was
      inferior for patients >= 547 days with MYCN-NA neuroblastoma (P < 0.0001), and
      within this cohort, serum ferritin >= 96 ng/ml was associated with inferior EFS
      (P = 0.02). For patients <547 days of age with MYCN-NA tumors, serum ferritin
      levels were prognostic of overall survival (OS) (P = 0.04) and chromosome 11q
      aberration was prognostic of EFS (P = 0.03). CONCLUSIONS: Among patients with
      INSS Stage 3 neuroblastoma patients, age at diagnosis, MYCN status and histology
      predict outcome. Patients <547 days of age with MYCN-NA tumors that lack
      chromosome 11q aberrations or those with serum ferritin <96 ng/ml have excellent
      prognosis and should be considered for therapy reduction. Prospective clinical
      trials are needed to identify optimal therapy for those patients >= 547 days of
      age with undifferentiated histology or elevated serum ferritin.

PMID- 25044742
TI  - Pain in patients with borderline personality disorder.
AB  - OBJECTIVE: Patients with borderline personality disorder (BPD) frequently present
      to primary care physicians and specialists with pain problems. The aims of the
      current study are to (1) examine the prevalence of pain symptoms in patients with
      a diagnosis of BPD compared with a diagnosis of another personality disorder and
      (2) identify the factors that predict pain experienced in patients with BPD.
      METHODS: Two hundred and ninety inpatients meeting Revised Diagnostic Interview
      for Borderlines and DSM-III-R criteria for BPD and 72 patients who met DSM-III-R
      criteria for another personality disorder were assessed at baseline using
      semistructured interviews and self-report measures. Ratings of pain were assessed
      16 years after baseline diagnosis and compared between diagnostic groups using t
      tests. Regression analyses were used to identify predictors of pain among
      patients with BPD. RESULTS: Patients with BPD are more likely to experience pain
      and rate their pain as more severe than patients with other personality
      disorders. In multivariable regression models, there were three significant
      predictors of severity of pain among patients with BPD: older age, the presence
      of major depressive disorder, and the severity of childhood abuse other than
      sexual abuse. CONCLUSION: Patients with BPD report significant pain, which
      interferes with their lives. A focus on the management of medical and psychiatric
      comorbidities may improve their long-term functioning.

PMID- 25044744
TI  - TRIP6 regulates neural stem cell maintenance in the postnatal mammalian
      subventricular zone.
AB  - BACKGROUND: Postnatal neurogenesis persists throughout life in the subventricular
      zone (SVZ)-olfactory bulb pathway in mammals. Extrinsic or intrinsic factors have
      been revealed to regulate neural stem cell (NSC) properties and neurogenesis.
      Thyroid hormone receptor interacting protein 6 (TRIP6) belongs to zyxin family of
      LIM proteins, which have been shown to interact with various proteins to mediate
      cellular functions. However, the role of TRIP6 in NSCs is still unknown. RESULTS:
      By performing double immunofluorescence staining, we found that TRIP6 was
      expressed by Sox2-positive NSCs in embryonic and postnatal mouse forebrains. To
      study the function of TRIP6 in NSCs, we performed overexpression and knockdown
      experiments with neurospheres derived from postnatal day 7 SVZ. We found that
      TRIP6 was necessary and sufficient for self-renewal and proliferation of NSCs,
      but inhibited their differentiation. To further investigate the mechanism of
      TRIP6 in NSCs, we performed Luciferase reporter assay and found that TRIP6
      activated Notch signaling, a pathway required for NSC self-renewal. CONCLUSIONS:
      Our data suggest that TRIP6 regulates NSC maintenance and it may be a new marker
      for NSCs.

PMID- 25044745
TI  - Mutation of POC1B in a severe syndromic retinal ciliopathy.
AB  - We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA),
      Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next
      generation sequencing for excluding mutations in known LCA and JBTS genes,
      homozygosity mapping, and whole-exome sequencing identified a homozygous missense
      variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis,
      basal body, and centrosome integrity. In silico modeling suggested a requirement
      of p.Arg106 for the formation of the third WD40 repeat and a protein interaction
      interface. In human and mouse retina, POC1B localized to the basal body and
      centriole adjacent to the connecting cilium of photoreceptors and in synapses of
      the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys
      and retinal degeneration with shortened and reduced photoreceptor connecting
      cilia, compatible with the human syndromic ciliopathy. A recent study describes
      homozygosity for p.Arg106ProPOC1B in a family with nonsyndromic cone-rod
      dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be
      highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either
      isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B
      is required for retinal integrity, and we propose POC1B mutations as a probable
      cause for JBTS with severe PKD.

PMID- 25044747
TI  - Decreased limbic and increased fronto-parietal connectivity in unmedicated
      patients with obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is characterized by recurrent intrusive
      thoughts and ritualized, repetitive behaviors, or mental acts. Convergent
      experimental evidence from neuroimaging and neuropsychological studies supports
      an orbitofronto-striato-thalamo-cortical dysfunction in OCD. Moreover, an over
      excitability of the amygdala and over monitoring of thoughts and actions
      involving the anterior cingulate, frontal and parietal cortex has been proposed
      as aspects of pathophysiology in OCD. We chose a data driven, graph theoretical
      approach to investigate brain network organization in 17 unmedicated OCD patients
      and 19 controls using resting-state fMRI. OCD patients showed a decreased
      connectivity of the limbic network to several other brain networks: the basal
      ganglia network, the default mode network, and the executive/attention network.
      The connectivity within the limbic network was also found to be decreased in OCD
      patients compared to healthy controls. Furthermore, we found a stronger
      connectivity of brain regions within the executive/attention network in OCD
      patients. This effect was positively correlated with disease severity. The
      decreased connectivity of limbic regions (amygdala, hippocampus) may be related
      to several neurocognitive deficits observed in OCD patients involving implicit
      learning, emotion processing and expectation, and processing of reward and
      punishment. Limbic disconnection from fronto-parietal regions relevant for (re)
      appraisal may explain why intrusive thoughts become and/or remain threatening to
      patients but not to healthy subjects. Hyperconnectivity within the
      executive/attention network might be related to OCD symptoms such as excessive
      monitoring of thoughts and behavior as a dysfunctional strategy to cope with
      threat and uncertainty.

PMID- 25044746
TI  - Neonatal overexpression of estrogen receptor-alpha alters midbrain dopamine
      neuron development and reverses the effects of low maternal care in female
      offspring.
AB  - Maternal behavior is dependent on estrogen receptor-alpha (ERalpha; Esr1) and
      oxytocin receptor (OTR) signaling in the medial preoptic area (MPOA) of the
      hypothalamus, as well as dopamine signaling from the ventral tegmental area (VTA)
      to forebrain regions. Previous studies in rats indicate that low levels of
      maternal care, particularly licking/grooming (LG), lead to reduced levels of MPOA
      ERalpha and VTA dopamine neurons in female offspring and predict lower levels of
      postpartum maternal behavior by these offspring. The aim of this study was to
      determine the functional impact on maternal behavior of neonatal manipulation of
      ERalpha in females that had experienced low versus high levels of postnatal
      maternal LG. Adenovirus expressing ESR1 was targeted to the MPOA in female pups
      from low and high LG litters on postnatal day 2-3. Overexpression of ESR1 in low
      LG offspring elevated the level of ERalpha-immunoreactive cells in the MPOA and
      of tyrosine hydroxylase cells in the VTA to that observed in high LG females.
      Amongst juvenile female low LG offspring, ESR1 overexpression also decreased the
      latency to engage in maternal behavior toward donor pups. These results show that
      virally mediated expression of ESR1 in the neonatal rat hypothalamus results in
      lasting changes in ESR1 expression through the juvenile period, and can "rescue"
      hormone receptor levels and behavior of offspring reared by low LG dams,
      potentially mediated by downstream alterations within reward circuitry. Thus, the
      transmission of maternal behavior from one generation to the next can be
      augmented by neonatal ERalpha in the MPOA.

PMID- 25044748
TI  - Distal Xq28 microdeletions: clarification of the spectrum of contiguous gene
      deletions involving ABCD1, BCAP31, and SLC6A8 with a new case and review of the
      literature.
AB  - The contiguous ABCD1/DXS1375E (BCAP31) deletion syndrome (CADDS) is a rare X
      linked contiguous gene deletion syndrome with a severe clinical phenotype that
      includes marked delays, significant growth failure, liver dysfunction, and early
      death. The X-linked creatine transporter deficiency is a considerably more common
      and a cause of X-linked intellectual disability; however, multi-exon deletions of
      the creatine transporter are rare. We report the fifth case of CADDS, who also
      has a deletion of the X-linked creatine transporter. We also review reported
      cases of deletions in this region in order to clarify the clinical spectrum of
      contiguous microdeletions in this region.

PMID- 25044749
TI  - Electrocatalysis of water oxidation by H2O-capped iridium-oxide nanoparticles
      electrodeposited on spectroscopic graphite.
AB  - Electrocatalysis of water oxidation by 1.54 nm IrOx nanoparticles (NPs)
      immobilized on spectroscopic graphite electrodes was demonstrated to proceed with
      a higher efficiency than on all other, hitherto reported, electrode supports.
      IrOx NPs were electrodeposited on the graphite surface, and their
      electrocatalytic activity for water oxidation was correlated with the surface
      concentrations of different redox states of IrOx as a function of the deposition
      time and potential. Under optimal conditions, the overpotential of the reaction
      was reduced to 0.21 V and the electrocatalytic current density was 43 mA cm(-2)
      at 1 V versus Ag/AgCl (3 M KCl) and pH 7. These results beneficially compete with
      previously reported electrocatalytic oxidations of water by IrOx NPs
      electrodeposited onto glassy carbon and indium tin oxide electrodes and provide
      the basis for the further development of efficient IrOx NP-based electrocatalysts
      immobilized on high-surface-area carbon electrode materials.

PMID- 25044752
TI  - Defect chemistry of singly and doubly doped ceria: correlation between ion
      transport and energetics.
AB  - Earlier studies have shown a strong correlation between the enthalpy of
      formation, DeltaHf,ox , and the ionic conductivity, sigmai , near room
      temperature in doped ceria systems, which are promising solid electrolytes for
      intermediate-temperature solid oxide fuel cells (IT-SOFCs). The present work
      demonstrates that this correlation holds at the operating temperature of IT
      SOFCs, 600-700  degrees C. Solid solutions of Ce1-x Ndx O2-0.5x , Ce1-x Smx O2
      0.5x , and Ce1-x Sm0.5x Nd0.5x O2-0.5x are studied. The DeltaHf,ox at 702 
      degrees C is determined by considering the excess heat content between 25 and 702
      degrees C combined with the value of DeltaHf,ox at 25  degrees C. Both sigmai
      and DeltaHf,ox show maxima at x=0.15 and 0.20 for the singly and doubly doped
      ceria, respectively, suggesting that the number of mobile oxygen vacancies in
      these solid solutions reaches a maximum near those compositions. An increase in
      temperature results in a shift of the maximum in both DeltaHf,ox and sigmai
      towards higher concentrations. This shift results from a gradual increase in
      dissociation of the defect associates. 

PMID- 25044751
TI  - Development of a porcine renal extracellular matrix scaffold as a platform for
      kidney regeneration.
AB  - Acellular scaffolds, possessing an intact three-dimensional extracellular matrix
      (ECM) architecture and biochemical components, are promising for regeneration of
      complex organs, such as the kidney. We have successfully developed a porcine
      renal acellular scaffold and analyzed its physical/biochemical characteristics,
      biocompatibility, and kidney reconstructive potential. Segmented porcine kidney
      cortexes were treated with either 1% (v/v) Triton X-100 (Triton) or sodium
      dodecyl sulfate (SDS). Scanning electron microscopy showed both treatments
      preserved native tissue architecture, including porosity and composition.
      Swelling behavior was higher in the Triton-treated compared with the SDS-treated
      scaffold. Maximum compressive strength was lower in the Triton-treated compared
      with the SDS-treated scaffold. Attenuated total reflective-infrared spectroscopy
      showed the presence of amide II (-NH) in both scaffolds. Furthermore, richer ECM
      protein and growth factor contents were observed in the Triton-treated compared
      with SDS-treated scaffold. Primary human kidney cell adherence, viability, and
      proliferation were enhanced on the Triton-treated scaffold compared with SDS
      treated scaffold. Following murine in vivo implantation, tumorigenecity was
      absent for both scaffolds after 8 weeks and in the Triton-treated scaffold only,
      glomeruli-like structure formation and neovascularity were observed. We
      identified 1% Triton X-100 as a more suitable decellularizing agent for porcine
      renal ECM scaffolds prior to kidney regeneration.

PMID- 25044753
TI  - A quantitative view of charge transfer in the hydrogen bond: the water dimer
      case.
AB  - The hydrogen bond represents a fundamental intermolecular interaction that binds
      molecules in vapor and liquid water. A crucial and debated aspect of its
      electronic structure and chemistry is the charge transfer (CT) accompanying it.
      Much effort has been devoted, in particular, to the study of the smallest
      prototype system, the water dimer, but even here results and interpretations
      differ widely. In this paper, we reassess CT in the water dimer by using charge
      displacement analysis. Besides a reliable estimate of the amount of CT (14.6 me)
      that characterizes the system, our study provides an unambiguous context, and
      very useful bounds, within which CT effects may be evaluated, crucially including
      the associated energy stabilization. 

PMID- 25044750
TI  - Development of diaminoquinazoline histone lysine methyltransferase inhibitors as
      potent blood-stage antimalarial compounds.
AB  - Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for
      the discovery of novel antimalarial drugs. Previously we demonstrated the potent
      in vitro and in vivo antimalarial activity of (1-benzyl-4-piperidyl)[6,7
      dimethoxy-2-(4-methyl-1,4-diazepin-1-yl)-4-quinazolinyl]amine (BIX01294; 1), a
      known human G9a inhibitor, together with its dose-dependent effects on histone
      methylation in the malarial parasite. This work describes our initial medicinal
      chemistry efforts to optimise the diaminoquinazoline chemotype for antimalarial
      activity. A variety of analogues were designed by substituting the 2 and 4
      positions of the quinazoline core, and these molecules were tested against
      Plasmodium falciparum (3D7 strain). Several analogues with IC50 values as low as
      18.5 nM and with low mammalian cell toxicity (HepG2) were identified. Certain
      pharmacophoric features required for antimalarial activity were found to be
      analogous to the previously published SAR of these analogues for G9a inhibition,
      thereby suggesting potential similarities between the malarial and human HKMT
      targets of this chemotype. Physiochemical, in vitro activity, and in vitro
      metabolism studies were also performed for a select set of potent analogues to
      evaluate their potential as antimalarial leads. 

PMID- 25044755
TI  - Separation of cationic analytes by nonionic micellar electrokinetic
      chromatography using polyoxyethylene lauryl ether surfactants with different
      polyoxyethylene length.
AB  - Although nonionic micellar electrokinetic chromatography is used for the
      separation of charged compounds that are not easily separated by capillary zone
      electrophoresis, the effect of the hydrophilic moiety of the nonionic surfactant
      has not been studied well. In this study, the separation of ultraviolet-absorbing
      amino acids was studied in electrokinetic chromatography using neutral
      polyoxyethylene lauryl ether surfactants (Adekatol) in the separation solution.
      The effect of the polyethylene moiety (the number of repeating units was from 6.5
      to 50) of the hydrophobic test amino acids (methionine, tryptophan, and tysorine)
      was studied using a 10 cm effective length capillary. The separation mechanism
      was based on hydrophobic as well as hydrogen bonding interactions at the micellar
      surface, which was made of the polyoxyethylene moiety. The length of the
      polyoxyethylene moiety of the surfactants was not important in nonionic micellar
      electrokinetic chromatography mode. 

PMID- 25044754
TI  - Phenylpropenoic acid glucoside augments pancreatic beta cell mass in high-fat
      diet-fed mice and protects beta cells from ER stress-induced apoptosis.
AB  - SCOPE: A major goal of diabetes therapy is to identify novel drugs that preserve
      or expand pancreatic beta cell mass. Here, we examined the effect of a
      phenylpropenoic acid glucoside (PPAG) on the beta cell mass, and via which
      mechanism this effect is established. METHODS AND RESULTS: Mice were fed a high
      fat and fructose-containing diet to induce obesity and hyperglycemia. PPAG
      treatment protected obese mice from diet-induced hyperglycemia and resulted in a
      tripling of beta cell mass. The effect of the phytochemical on beta cell mass was
      neither due to increased proliferation, as determined by Ki67 immunostaining, nor
      to neogenesis, which was assessed by genetic lineage tracing. TUNEL staining
      revealed suppressed apoptosis in PPAG-treated obese mice. In vitro, PPAG
      protected beta cells from palmitate-induced apoptosis. It protected beta cells
      against ER stress by increasing expression of antiapoptotic B-cell lymphoma 2
      (BCL2) protein without affecting proapoptotic signals. CONCLUSIONS: We identified
      an antidiabetic phytochemical that protects pancreatic beta cells from ER stress
      and apoptosis induced by high-fat diet/lipotoxicity. At the tissue level, this
      led to a tripling of beta cell mass. At the molecular level, the protective
      effect of the phytochemical was mediated by increasing BCL2 expression in beta
      cells.

PMID- 25044756
TI  - Polarization imaging and classification of Jurkat T and Ramos B cells using a
      flow cytometer.
AB  - Label-free and rapid classification of cells can have awide range of applications
      in biology. We report a robust method of polarization diffraction imaging flow
      cytometry (p-DIFC) for achieving this goal. Coherently scattered light signals
      are acquired from single cells excited by a polarized laser beam in the form of
      two cross-polarized diffraction images. Image texture and intensity parameters
      are extracted with a gray level co-occurrence matrix (GLCM) algorithm to obtain
      an optimized set of feature parameters as the morphological "fingerprints" for
      automated cell classification. We selected the Jurkat T cells and Ramos B cells
      to test the p-DIFC method's capacity for cell classification. After detailed
      statistical analysis, we found that the optimized feature vectors yield
      accuracies of classification between the Jurkat and Ramos ranging from 97.8% to
      100% among different cell data sets. Confocal imaging and three-dimensional
      reconstruction were applied to gain insights on the ability of p-DIFC method for
      classifying the two cell lines of highly similar morphology. Based on these
      results we conclude that the p-DIFC method has the capacity to discriminate cells
      of high similarity in their morphology with "fingerprints" features extracted
      from the diffraction images, which may be attributed to subtle but statistically
      significant differences in the nucleus-to-cell volume ratio in the case of Jurkat
      and Ramos cells.

PMID- 25044757
TI  - Antitumor efficacy, pharmacokinetic and biodistribution studies of the anticancer
      peptide CIGB-552 in mouse models.
AB  - Accumulation of the COMMD1 protein as a druggable pharmacology event to target
      cancer cells has not been evaluated so far in cancer animal models. We have
      previously demonstrated that a second-generation peptide, with cell-penetrating
      capacity, termed CIGB-552, was able to induce apoptosis mediated by stabilization
      of COMMD1. Here, we explore the antitumor effect by subcutaneous administration
      of CIGB-552 in a therapeutic schedule. Outstandingly, a significant delay of
      tumor growth was observed at 0.2 and 0.7 mg/kg (p < 0.01) or 1.4 mg/kg (p <
      0.001) after CIGB-552 administration in both syngeneic murine tumors and patient
      derived xenograft models. Furthermore, we evidenced that (131)I-CIGB-552 peptide
      was actually accumulated in the tumors after administration by subcutaneous
      route. A typical serine-proteases degradation pattern for CIGB-552 in BALB/c mice
      serum was identified. Further, biological characterization of the main
      metabolites of the peptide CIGB-552 suggests that the cell-penetrating capacity
      plays an important role in the cytotoxic activity. This report is the first in
      describing the antitumor effect induced by systemic administration of a peptide
      that targets COMMD1 for stabilization. Moreover, our data reinforce the
      perspectives of CIGB-552 for cancer targeted therapy.

PMID- 25044759
TI  - Direct analytical sample quality assessment for biomarker investigation:
      qualifying cerebrospinal fluid samples.
AB  - Measurement of biochemical markers represents an important aid to clinicians in
      the early diagnosis and prognosis of neurological diseases. Many factors can
      contribute to increase the chances that a biomarker study becomes successful. In
      a cerebrospinal fluid analysis (CSF), more than 84% of laboratory errors can be
      attributed to several preanalytical variables that include CSF collection,
      storage, and freeze thawing cycles. In this concept paper, we focus on some
      critical issues arising from basic proteomics investigation in order to highlight
      some key elements of CSF quality control. Furthermore, we propose a direct
      assessment of sample quality (DASQ) by applying a fast MALDI-TOF-MS methodology
      to evaluate molecular features of sample degradation and oxidation. We propose
      DASQ as a fast and simple initial step to be included in large-scale projects for
      neurological biomarker studies. In fact, such a procedure will improved the
      development of standardized protocols in order to have well-characterized CSF
      biobanks.

PMID- 25044758
TI  - Genome-wide association study of height-adjusted BMI in childhood identifies
      functional variant in ADCY3.
AB  - OBJECTIVE: Genome-wide association studies (GWAS) of BMI are mostly undertaken
      under the assumption that "kg/m(2) " is an index of weight fully adjusted for
      height, but in general this is not true. The aim here was to assess the
      contribution of common genetic variation to a adjusted version of that phenotype
      which appropriately accounts for covariation in height in children. METHODS: A
      GWAS of height-adjusted BMI (BMI[x] = weight/height(x) ), calculated to be
      uncorrelated with height, in 5809 participants (mean age 9.9 years) from the Avon
      Longitudinal Study of Parents and Children (ALSPAC) was performed. RESULTS: GWAS
      based on BMI[x] yielded marked differences in genomewide results profile. SNPs in
      ADCY3 (adenylate cyclase 3) were associated at genome-wide significance level
      (rs11676272 (0.28 kg/m(3.1) change per allele G (0.19, 0.38), P = 6 * 10(-9) ).
      In contrast, they showed marginal evidence of association with conventional BMI
      [rs11676272 (0.25 kg/m(2) (0.15, 0.35), P = 6 * 10(-7) )]. Results were
      replicated in an independent sample, the Generation R study. CONCLUSIONS:
      Analysis of BMI[x] showed differences to that of conventional BMI. The
      association signal at ADCY3 appeared to be driven by a missense variant and it
      was strongly correlated with expression of this gene. Our work highlights the
      importance of well understood phenotype use (and the danger of convention) in
      characterising genetic contributions to complex traits.

PMID- 25044760
TI  - Pyrrolysine-inspired protein cyclization.
AB  - The pyrrolysine translational machinery has been extensively explored for the
      production of recombinant proteins containing a variety of "site-specific" non
      canonical amino acids for both in vitro and in vivo biochemical studies. In this
      study, we report the first use of this technology for the production of branched
      cyclic proteins with a tadpole-like topology. As a proof of concept, we fused the
      well-studied RGD peptide to the C terminus of an mCherry reporter protein.
      Previous studies have shown that cyclization of the RGD peptide enhances its
      internalization into cells compared to its linear counterpart. The cellular
      uptake efficiencies of mCherry-cyclo(RGD), mCherry-linear(RGD), and wild-type
      mCherry determined by flow cytometry follow the trends expected, thereby
      confirming the feasibility and potential utility of this cyclization approach. 

PMID- 25044761
TI  - Electron delocalization in a rigid cofacial naphthalene-1,8:4,5
      bis(dicarboximide) dimer.
AB  - Investigating through-space electronic communication between discrete cofacially
      oriented aromatic pi-systems is fundamental to understanding assemblies as
      diverse as double-stranded DNA, organic photovoltaics and thin-film transistors.
      A detailed understanding of the electronic interactions involved rests on making
      the appropriate molecular compounds with rigid covalent scaffolds and pi-pi
      distances in the range of ca. 3.5 A. Reported herein is an enantiomeric pair of
      doubly-bridged naphthalene-1,8:4,5-bis(dicarboximide) (NDI) cyclophanes and the
      characterization of four of their electronic states, namely 1) the ground state,
      2) the exciton coupled singlet excited state, 3) the radical anion with strong
      through-space interactions between the redox-active NDI molecules, and 4) the
      diamagnetic diradical dianion using UV/Vis/NIR, EPR and ENDOR spectroscopies in
      addition to X-ray crystallography. Despite the unfavorable Coulombic repulsion,
      the singlet diradical dianion dimer of NDI shows a more pronounced intramolecular
      pi-pi stacking interaction when compared with its neutral analog. 

PMID- 25044763
TI  - Synthesis of natural products containing cyclohexane units utilizing the Ferrier
      carbocyclization reaction.
AB  - The Ferrier carbocyclization reaction is one of the most powerful transformations
      of carbohydrates. This reaction provides enantiomerically pure cyclohexanone
      derivatives from aldohexoses, and is particularly useful in the chiral pool
      synthesis of cyclohexane-containing natural products from carbohydrates. We have
      investigated the synthesis of natural products utilizing the Ferrier
      carbocyclization reaction. This account provides a brief overview of the Ferrier
      carbocyclization and its application to natural product synthesis. The utility
      and versatility of the Ferrier carbocyclization reaction are showcased with the
      syntheses of hygromycin A, lycoricidine, actinobolin, galanthamine, and morphine
      starting from carbohydrates. 

PMID- 25044765
TI  - Single nanoparticle couplers for plasmonic waveguides.
AB  - A single nanoparticle antenna, can be used as an efficient coupler for plasmonic
      nanowire waveguides. The coup-ling of light into the surface plasmon polaritons
      on a nanowire can be suppressed or enhanced depending on the surface plasmon
      resonances of the nanoantenna. The coupler is compacted and can be simply
      controlled using focus ion beam. 

PMID- 25044764
TI  - Oscillatory fluid flow influences primary cilia and microtubule mechanics.
AB  - Many tissues are sensitive to mechanical stimuli; however, the
      mechanotransduction mechanism used by cells remains unknown in many cases. The
      primary cilium is a solitary, immotile microtubule-based extension present on
      nearly every mammalian cell which extends from the basal body. The cilium is a
      mechanosensitive organelle and has been shown to transduce fluid flow-induced
      shear stress in tissues, such as the kidney and bone. The majority of
      microtubules assemble from the mother centriole (basal body), contributing
      significantly to the anchoring of the primary cilium. Several studies have
      attempted to quantify the number of microtubules emanating from the basal body
      and the results vary depending on the cell type. It has also been shown that
      cellular response to shear stress depends on microtubular integrity. This study
      hypothesizes that changing the microtubule attachment of primary cilia in
      response to a mechanical stimulus could change primary cilia mechanics and,
      possibly, mechanosensitivity. Oscillatory fluid flow was applied to two different
      cell types and the microtubule attachment to the ciliary base was quantified. For
      the first time, an increase in microtubules around primary cilia both with time
      and shear rate in response to oscillatory fluid flow stimulation was
      demonstrated. Moreover, it is presented that the primary cilium is required for
      this loading-induced cellular response. This study has demonstrated a new role
      for the cilium in regulating alterations in the cytoplasmic microtubule network
      in response to mechanical stimulation, and therefore provides a new insight into
      how cilia may regulate its mechanics and thus the cells mechanosensitivity.

PMID- 25044766
TI  - Selective photoelectrochemical reduction of aqueous CO2 to CO by solvated
      electrons.
AB  - Reduction of CO2 by direct one-electron activation is extraordinarily difficult
      because of the -1.9 V reduction potential of CO2. Demonstrated herein is
      reduction of aqueous CO2 to CO with greater than 90% product selectivity by
      direct one-electron reduction to CO2(-) by solvated electrons. Illumination of
      inexpensive diamond substrates with UV light leads to the emission of electrons
      directly into water, where they form solvated electrons and induce reduction of
      CO2 to CO2(-). Studies using diamond were supported by studies using aqueous
      iodide ion (I(-)), a chemical source of solvated electrons. Both sources produced
      CO with high selectivity and minimal formation of H2 . The ability to initiate
      reduction reactions by emitting electrons directly into solution without surface
      adsorption enables new pathways which are not accessible using conventional
      electrochemical or photochemical processes.

PMID- 25044767
TI  - Fire in Australian savannas: from leaf to landscape.
AB  - Savanna ecosystems comprise 22% of the global terrestrial surface and 25% of
      Australia (almost 1.9 million km2) and provide significant ecosystem services
      through carbon and water cycles and the maintenance of biodiversity. The current
      structure, composition and distribution of Australian savannas have coevolved
      with fire, yet remain driven by the dynamic constraints of their bioclimatic
      niche. Fire in Australian savannas influences both the biophysical and
      biogeochemical processes at multiple scales from leaf to landscape. Here, we
      present the latest emission estimates from Australian savanna biomass burning and
      their contribution to global greenhouse gas budgets. We then review our
      understanding of the impacts of fire on ecosystem function and local surface
      water and heat balances, which in turn influence regional climate. We show how
      savanna fires are coupled to the global climate through the carbon cycle and fire
      regimes. We present new research that climate change is likely to alter the
      structure and function of savannas through shifts in moisture availability and
      increases in atmospheric carbon dioxide, in turn altering fire regimes with
      further feedbacks to climate. We explore opportunities to reduce net greenhouse
      gas emissions from savanna ecosystems through changes in savanna fire management.

PMID- 25044768
TI  - The changes of leukocyte telomere length and telomerase activity after
      sitagliptin intervention in newly diagnosed type 2 diabetes.
AB  - BACKGROUND: In recent years, increasing evidence suggests a potential importance
      of telomere biology in type 2 diabetes. The aim of this study was to determine
      whether sitagliptin, a medicine generally used in diabetes, can influence the
      telomere and telomerase in newly diagnosed type 2 diabetic patients. METHODS:
      Type 2 diabetic patients (T2D, n = 38) and non-diabetic subjects (control, n =
      31) were randomly selected from the outpatient of Tongji Hospital, Tongji Medical
      College, Huazhong university of Science and Technology. Leukocyte telomere length
      ratio was measured using a quantitative polymerase chain reaction and was
      analysed. Telomerase activity was measured by polymerase chain reaction enzyme
      linked immunosorbent assay method. Peripheral insulin resistance (homeostasis
      model assessment) was calculated from fasting plasma glucose and fasting plasma
      insulin. RESULTS: Telomere length of the type 2 diabetic patients (1.58 +/- 0.57)
      was significantly shorter than those of control subjects (3.98 +/- 0.90) and was
      significantly elongated after intervention by sitagliptin. There was no
      significant difference between the T2D and control group in telomerase activity,
      and the treatment of sitagliptin in T2D group showed no significant effect on the
      telomerase activity. CONCLUSIONS: In type 2 diabetes patients, leukocyte telomere
      length is significantly reduced, whereas the telomerase activity seems less
      influenced. Sitagliptin might protect beta-cells in the pancreas by elongating
      the telomere length.

PMID- 25044769
TI  - Synchronized mammalian cell culture: part I--a physical strategy for synchronized
      cultivation under physiological conditions.
AB  - Conventional analysis and optimization procedures of mammalian cell culture
      processes mostly treat the culture as a homogeneous population. Hence, the focus
      is on cell physiology and metabolism, cell line development, and process control
      strategy. Impact on cultivations caused by potential variations in cellular
      properties between different subpopulations, however, has not yet been evaluated
      systematically. One main cause for the formation of such subpopulations is the
      progress of all cells through the cell cycle. The interaction of potential cell
      cycle specific variations in the cell behavior with large-scale process
      conditions can be optimally determined by means of (partially) synchronized
      cultivations, with subsequent population resolved model analysis. Therefore, it
      is desirable to synchronize a culture with minimal perturbation, which is
      possible with different yield and quality using physical selection methods, but
      not with frequently used chemical or whole-culture methods. Conventional
      nonsynchronizing methods with subsequent cell-specific, for example, flow
      cytometric analysis, can only resolve cell-limited effects of the cell cycle. In
      this work, we demonstrate countercurrent-flow centrifugal elutriation as a useful
      physical method to enrich mammalian cell populations within different phases of a
      cell cycle, which can be further cultivated for synchronized growth in
      bioreactors under physiological conditions. The presented combined approach
      contrasts with other physical selection methods especially with respect to the
      achievable yield, which makes it suitable for bioreactor scale cultivations. As
      shown with two industrial cell lines (CHO-K1 and human AGE1.HN), synchronous
      inocula can be obtained with overall synchrony degrees of up to 82% in the G1
      phase, 53% in the S phase and 60% in the G2/M phase, with enrichment factors
      (Ysync) of 1.71, 1.79, and 4.24 respectively. Cells are able to grow with
      synchrony in bioreactors over several cell cycles. This strategy, combined with
      population-resolved model analysis and parameter extraction as described in the
      accompanying paper, offers new possibilities for studies of cell lines and
      processes at levels of cell cycle and population under physiological conditions.

PMID- 25044770
TI  - Brillouin spectroscopy as a new method of screening for increased CSF total
      protein during bacterial meningitis.
AB  - Bacterial meningitis is a disease of pronounced clinical significance, especially
      in the developing world. Immediate treatment with antibiotics is essential, and
      no single test can provide a conclusive diagnosis. It is well established that
      elevated total protein in cerebrospinal fluid (CSF) is associated with bacterial
      meningitis. Brillouin spectroscopy is a widely used optical technique for
      noninvasive determination of the elastic moduli of materials. We found that
      elevated protein levels in CSF alter the fluid elasticity sufficiently to be
      measurable by Brillouin spectroscopy, with model healthy and diseased fluids
      distinguishable to marked significance (P = 0.014), which increases with sample
      concentration by dialysis. Typical raw output of a 2-stage VIPA Brillouin
      spectrometer: inelastically scattered Brillouin peaks (arrows) and elastically
      scattered incident radiation (center cross). 

PMID- 25044771
TI  - Sexual and asexual reproduction in the colonial ascidian Botryllus schlosseri.
AB  - The colonial tunicate Botryllus schlosseri is a widespread filter-feeding
      ascidian that lives in shallow waters and is easily reared in aquaria. Its
      peculiar blastogenetic cycle, characterized by the presence of three
      blastogenetic generations (filtering adults, buds, and budlets) and by recurrent
      generation changes, has resulted in over 60 years of studies aimed at
      understanding how sexual and asexual reproduction are coordinated and regulated
      in the colony. The possibility of using different methodological approaches, from
      classical genetics to cell transplantation, contributed to the development of
      this species as a valuable model organism for the study of a variety of
      biological processes. Here, we review the main studies detailing rearing, staging
      methods, reproduction and colony growth of this species, emphasizing the
      asymmetry in sexual and asexual reproduction potential, sexual reproduction in
      the field and the laboratory, and self- and cross-fertilization. These data,
      opportunely matched with recent tanscriptomic and genomic outcomes, can give a
      valuable help to the elucidation of some important steps in chordate evolution.

PMID- 25044772
TI  - Insulating and cooling effects of nasal endoscope sheaths and irrigation.
AB  - BACKGROUND: Heat generated at the tips of nasal endoscopes have been shown to
      reach temperatures high enough to cause thermal tissue injury. Endoscope sheaths
      have the potential to minimize the risk of thermal tissue injury. The purpose of
      this study was to assess the abilities of plastic and metal endoscope sheaths and
      sheath irrigation to insulate against dangerous scope tip temperatures. METHODS:
      A 4-mm 0-degree rigid nasal endoscope was used with light-emitting diode (LED)
      and xenon light sources (400-W LED, 300-W, and 175-W xenon) to assess scope tip
      temperature before and after endoscope sheath placement. Temperatures were
      assessed again after placement of each sheath, both before and after active
      saline irrigation. Scope tip temperature was measured using a noncontact infrared
      thermometer. RESULTS: The unsheathed rigid scope tip reached a maximal
      temperature after 10 minutes at 100% light source intensity. The 400-W LED and
      300-W xenon sources generated potentially dangerous scope tip temperatures
      exceeding 42 degrees C, whereas the 175-W xenon source never generated a maximal
      temperature over 32.6 degrees C. After placement of plastic and metal sheaths,
      mean scope tip temperatures were decreased by 2 degrees C (4.8%) and 2.2 degrees
      C (5.5%), respectively. After active saline irrigation, mean scope tip
      temperatures were decreased by 5.1 degrees C (12.6%) and 5.2 degrees C (12.8%),
      respectively. CONCLUSION: With modern light sources, nasal endoscopes have the
      potential to reach temperatures that may cause thermal tissue injury. Endoscope
      sheaths lead to decreases in scope temperatures, and the effect is greater with
      active irrigation. In addition to improving visualization, endoscope sheaths may
      decrease the risk of thermal tissue injury.

PMID- 25044773
TI  - Computer-automated focus lateralization of temporal lobe epilepsy using fMRI.
AB  - PURPOSE: To compare the performance of computer-automated diagnosis using
      functional magnetic resonance imaging (fMRI) interictal graph theory (CADFIG) to
      that achieved in standard clinical practice with MRI, for lateralizing the
      affected hemisphere in temporal lobe epilepsy (TLE). MATERIALS AND METHODS:
      Interictal resting state fMRI and high-resolution MRI were performed on 14 left
      and 10 right TLE patients. Functional topology measures were calculated from fMRI
      using graph theory, and used to lateralize the epileptogenic hemisphere using
      quadratic discriminant analysis. Leave-one-out cross-validation prediction
      accuracy of CADFIG was compared to performance based on expert manual analysis
      (MA) of MRI, using video EEG as the "gold standard" for focus lateralization.
      RESULTS: CADFIG correctly lateralized 95.8% (23/24) of cases, compared to 66.7%
      (16/24) with expert MA of MRI. Combining MA with CADFIG allowed all cases (24/24)
      to be correctly lateralized. CADFIG correctly identified the affected hemisphere
      for all patients (8/8) where MRI failed to lateralize. CONCLUSION: CADFIG based
      on fMRI lateralized the affected hemisphere in TLE with superior performance
      compared to expert MA of MRI. These results demonstrate that functional patterns
      in fMRI can be used with automated machine learning for diagnostic lateralization
      in TLE. Addition of fMRI-based tests to existing protocols for identifying the
      affected hemisphere in presurgical assessment can improve diagnostic accuracy and
      surgical outcome in TLE.

PMID- 25044774
TI  - Bimetallic NiCo functional graphene: an efficient catalyst for hydrogen-storage
      properties of MgH2.
AB  - Bimetallic NiCo functional graphene (NiCo/rGO) was synthesized by a facile one
      pot method. During the coreduction process, the as-synthesized ultrafine NiCo
      nanoparticles (NPs), with a typical size of 4-6 nm, were uniformly anchored onto
      the surface of reduced graphene oxide (rGO). The NiCo bimetal-supported graphene
      was found to be more efficient than their single metals. Synergetic catalysis of
      NiCo NPs and rGO was confirmed, which can significantly improve the hydrogen
      storage properties of MgH2. The apparent activation energy (E(a)) of the MgH2
      NiCo/rGO sample decreases to 105 kJ mol(-1), which is 40.7% lower than that of
      pure MgH2. More importantly, the as-prepared MgH2-NiCo/rGO sample can absorb 5.5
      and 6.1 wt% hydrogen within 100 and 350 s, respectively, at 300  degrees C under
      0.9 MPa H2 pressure. Further cyclic kinetics investigation indicates that MgH2
      NiCo/rGO nanocomposites have excellent cycle stability.

PMID- 25044775
TI  - gem-Difluorocarbadisaccharides: restoring the exo-anomeric effect.
AB  - Molecular mimicry is an essential part of the development of drugs and molecular
      probes. In the chemical glycobiology field, although many glycomimetics have been
      developed in the past years, it has been considered that many failures in their
      use are related to the lack of the anomeric effects in these analogues.
      Additionally, the origin of the anomeric effects is still the subject of virulent
      scientific debates. Herein, by combining chemical synthesis, NMR methods, and
      theoretical calculations, we show that it is possible to restore the anomeric
      effect for an acetal when replacing one of the oxygen atoms by a CF2 group. This
      result provides key findings in chemical sciences. On the one hand, it strongly
      suggests the key relevance of the stereoelectronic component of the anomeric
      effect. On the other hand, the CF2 analogue adopts the natural glycoside
      conformation, which might provide new avenues for sugar-based drug design. 

PMID- 25044776
TI  - Langmuir analysis of nanoparticle polyvalency in DNA-mediated adsorption.
AB  - Many nanoparticle adsorption processes are dictated by the collective
      interactions of surface-bound ligands. These adsorption processes define how
      nanoparticles interact with biological systems and enable the assembly of
      nanoparticle-based materials and devices. Herein, we present an approach for
      quantifying nanoparticle adsorption thermodynamics in a manner that satisfies the
      assumptions of the Langmuir model. Using this approach, we study the DNA-mediated
      adsorption of polyvalent anisotropic nanoparticles on surfaces and explore how
      deviations from model assumptions influence adsorption thermodynamics.
      Importantly, when combined with a solution-based van't Hoff analysis, we find
      that polyvalency plays a more important role as the individual interactions
      become weaker. Furthermore, we find that the free energy of anisotropic
      nanoparticle adsorption is consistent across multiple shapes and sizes of
      nanoparticles based on the surface area of the interacting facet. 

PMID- 25044777
TI  - Body mass index, waist circumference and skin-fold thickness in 12- to 14-year
      old Dutch adolescents: differences between 2003 and 2011.
AB  - OBJECTIVES: The aim of this study was to compare anthropometrics of 12- to 14
      year-old Dutch adolescents attending lower levels of education in 2011 with
      adolescents measured in 2003. METHODS: We used baseline data from two trials
      evaluating a school-based obesity prevention programme in 2003 (randomized
      controlled trial with 18 schools) and in 2011 (cluster controlled trial with 29
      schools). We measured adolescents' body height and weight, skin-fold thickness,
      and waist circumference in 2003 (n = 1000; response rate 76%) and 2011 (n = 1898;
      response rate 86%). We used multivariable multilevel linear or logistic
      regression analyses stratifying for gender, ethnicity and prevocational education
      track (vocational or theoretical) where appropriate. RESULTS: In boys, prevalence
      of overweight, waist circumference, triceps, biceps and subscapular skin-folds
      were significantly higher in 2011. This was also true for vocational girls,
      except for the subscapular skin-fold. Girls, attending the theoretical track, had
      a significantly larger waist circumference, but thinner subscapular and
      suprailiac skin-fold thickness in 2011. CONCLUSIONS: The increased prevalence of
      overweight and obesity in Dutch adolescents attending prevocational education is
      worrisome. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN87127361
      and Current Controlled Trials ISRCTN92755979.

PMID- 25044778
TI  - Ion distribution in quaternary-ammonium-functionalized aromatic polymers: effects
      on the ionic clustering and conductivity of anion-exchange membranes.
AB  - A series of copoly(arylene ether sulfone)s that have precisely two, three, or
      four quaternary ammonium (QA) groups clustered directly on single phenylene rings
      along the backbone are studied as anion-exchange membranes. The copolymers are
      synthesized by condensation polymerizations that involve either di-, tri-, or
      tetramethylhydroquinone followed by virtually complete benzylic bromination using
      N-bromosuccinimide and quaternization with trimethylamine. This synthetic
      strategy allows excellent control and systematic variation of the local density
      and distribution of QA groups along the backbone. Small-angle X-ray scattering of
      these copolymers shows extensive ionic clustering, promoted by an increasing
      density of QA on the single phenylene rings. At an ion-exchange capacity (IEC) of
      2.1 meq g(-1), the water uptake decreases with the increasing local density of QA
      groups. Moreover, at moderate IECs at 20  degrees C, the Br(-) conductivity of
      the densely functionalized copolymers is higher than a corresponding randomly
      functionalized polymer, despite the significantly higher water uptake of the
      latter. Thus, the location of multiple cations on single aromatic rings in the
      polymers facilitates the formation of a distinct percolating hydrophilic phase
      domain with a high ionic concentration to promote efficient anion transport,
      despite probable limitations by reduced ion dissociation. These findings imply a
      viable strategy to improve the performance of alkaline membrane fuel cells.

PMID- 25044779
TI  - Primary care for limited English-speaking patients and parents.
AB  - PURPOSE: The number of persons in the United States who have a primary language
      other than English has been steadily increasing for decades. The latest census
      information reveals that citizens with limited English proficiency (LEP)
      represent approximately 16% of the population. The inability to effectively
      communicate creates stark challenges in the delivery and receipt of health care.
      Language discordance in the healthcare setting has been firmly established as a
      source for health disparities among LEP patients and families. Poorer health
      outcomes are seen across the healthcare setting for LEP patients and children of
      LEP parents. DATA SOURCES: Scientific literature review, scholarly databases,
      Internet sites. CONCLUSIONS: There are various systems and methods that can be
      implemented in order to help improve health outcomes for LEP patients. There are
      benefits and challenges to each of the methods available for LEP patients and
      their providers. Improvements must be made on numerous levels including in
      clinical settings, in training curricula, and system wide. IMPLICATIONS FOR
      PRACTICE: The risks associated with decreased quality of communication between
      patient and provider merit an earnest consideration of the methods available for
      LEP patients and implementing some of these services for those patients.

PMID- 25044780
TI  - Cognition in breast cancer survivors: hormones versus depression.
AB  - BACKGROUND:  OBJECTIVE: Breast cancer survivors receiving hormone treatment
      and/or endorsing histories of receiving chemotherapy report changes in their
      cognitive capacity, which is often not supported by formal testing. To address
      these conflicting reports, this study examined survivors' applied cognitive
      capacity and its association with hormone treatment, depression, and selected
      demographics. METHODS: A descriptive, correlational, cross-sectional survey
      design was employed. There were 357 women who completed a survey comprised of 69
      questions. The survey included both investigator-developed questions and
      instruments from the PROMIS((r)) system. RESULTS: There were significant main
      effects for hormone therapy, race, and depression. Depression explained the
      largest portion of variance of the perceived decreases in cognitive function
      among breast cancer survivors. CONCLUSIONS: Survivor complaints of changes in
      cognitive function may be a predictor for evaluating the presence of mood
      disorders and less a function of hormone therapy or chemotherapy history.

PMID- 25044781
TI  - Engineering specificity changes on a RanBP2 zinc finger that binds single
      stranded RNA.
AB  - The realization that gene transcription is much more pervasive than previously
      thought and that many diverse RNA species exist in simple as well as complex
      organisms has triggered efforts to develop functionalized RNA-binding proteins
      (RBPs) that have the ability to probe and manipulate RNA function. Previously, we
      showed that the RanBP2-type zinc finger (ZF) domain is a good candidate for an
      addressable single-stranded-RNA (ssRNA) binding domain that can recognize ssRNA
      in a modular and specific manner. In the present study, we successfully
      engineered a sequence specificity change onto this ZF scaffold by using a
      combinatorial approach based on phage display. This work constitutes a foundation
      from which a set of RanBP2 ZFs might be developed that is able to recognize any
      given RNA sequence. 

PMID- 25044782
TI  - Incidence and timing of hypotension after transcervical carotid artery stenting:
      correlation with postoperative complications.
AB  - OBJECTIVES: To assess the incidence and timing of hypotension after carotid
      artery stenting (CAS) and its correlation with postoperative complications.
      BACKGROUND: CAS-associated postoperative hypotension has been linked to surgical
      morbidity and mortality, especially to stroke and cardiac complications. METHODS:
      Ninety-seven consecutive patients undergoing transcervical CAS were monitored for
      at least 12 hr after operation. Hypotension was defined as systolic blood
      pressure < 90 mm Hg. Patients were divided into three groups: normal blood
      pressure and early (<=6 hr) and late (>6 hr) hypotension. Complications were
      recorded. RESULTS: Hypotension occurred in 34% of the patients (early hypotension
      in 63% of them). Hypotension was recorded in 21.6% of patients during surgery and
      in 21.6%, 15.5%, and 1.0% at 6, 12, and 24 hr postoperatively. Bradycardia
      occurred in 26.8% during operation and in 25.8%, 13.4%, and 10.3% at 6, 12, and
      24 hr after surgery. Intraoperative bradycardia (P = 0.01) and hypotension (P =
      0.02) were predictors of postoperative hypotension. The overall rate of
      complications was 5% without differences between the study groups. The mean
      length of stay was 3, 3.6, and 2.8 days in the normotensive, early hypotension,
      and late hypotension groups, respectively. CONCLUSIONS: Most postoperative
      hypotension episodes occurred within the first 6 hr, and more than one-third
      between the 6 and 12 hr post-procedure. All patients with late hypotension were
      asymptomatic. There was no difference in complications between the study groups.
      In patients undergoing ambulatory CAS, hemodynamic monitoring in the
      postoperative period is particularly important during the first 12 hr.

PMID- 25044783
TI  - Defence styles in a sample of forensic patients with personality disorder.
AB  - BACKGROUND: Ego defences, often considered central to clinical work, have
      received surprisingly little attention in the forensic literature. METHOD: In
      this exploratory study, 114 male inpatients completed the Defence Style
      Questionnaire (DSQ) following their admission to a specialist personality
      disorder (PD) service. Change in DSQ scores over time was examined using mixed
      effects models for those (n = 48) remaining in treatment for at least 18 months.
      RESULTS: Defensive functioning at baseline was less mature in comparison with non
      clinical norms, with two other non-forensic PD samples, and with a male
      paedophile sample, but was unrelated to criminal history. Axis II severity was
      negatively associated with overall defensive functioning (ODF). Antisocial PD was
      positively associated with a maladaptive defence style. Borderline PD was
      negatively associated with self-sacrificing defences. Avoidant PD was negatively
      associated with both self-sacrificing and adaptive styles. Non-completion of
      treatment was predicted by low ODF scores and high maladaptive defence style
      scores at baseline. ODF improved significantly over time in treatment and was
      predicted by strong antisocial and weak schizotypal PD pathologies. CONCLUSIONS:
      Defence style, as measured by the DSQ, appears to have the potential to inform
      assessment and measure change in this group of offenders.

PMID- 25044784
TI  - Coming into focus: the role of extracellular matrix in vertebrate optic cup
      morphogenesis.
AB  - The vertebrate eye acquires its basic form during the process of optic cup
      morphogenesis, during which the optic vesicle emerges from the brain
      neuroepithelium and, through a series of cell and tissue movements, transforms
      itself into the multilayered optic cup, containing neural retina (comprised of
      retinal progenitors), retinal pigmented epithelium, and the lens, which is
      derived from the overlying ectoderm. While great strides have been made to
      understand the developmental signals controlling specification, patterning, and
      differentiation of the optic cup, only in recent years have the cellular and
      molecular bases of optic cup morphogenesis begun to be unraveled. One critical
      component of the morphogenetic process is the extracellular matrix: the complex,
      glycoprotein-rich layer that surrounds the optic vesicle and lens. Though the
      extracellular matrix has long been visualized by classical histological
      techniques and postulated to play various roles in optic cup development, its
      functional role was uncertain. This is now beginning to change, as live imaging
      techniques, quantitative image analyses, molecular genetics and in vitro models
      yield new insights into the process of optic cup morphogenesis and the specific
      influences of particular extracellular matrix components and their associated
      signaling pathways.

PMID- 25044785
TI  - Activation of the neurokinin 3 receptor promotes filopodia growth and sprouting
      in rat embryonic hypothalamic cells.
AB  - Members of the tachykinin family have trophic effects on developing neurons. The
      tachykinin neurokinin 3 receptor (NK3R) appears early in embryonic development;
      during the peak birthdates of hypothalamic neurons, but its involvement in neural
      development has not been examined. To address its possible role, immortalized
      embryonic hypothalamic neurons (CLU209) were treated with CellMask, a plasma
      membrane stain, or the membranes were imaged in CLU209 cells that were
      transfected with a pEGFP-NK3R expression vector. Nontransfected cells and
      transfected cells were then treated with senktide, a NK3R agonist, or Dulbecco's
      Modified Eagle's Medium (DMEM) and time-lapse confocal images were captured for
      the following 30 min. Compared to DMEM, senktide treatment led to filopodia
      initiation from the soma of both nontransfected and transfected CLU209 cells.
      These filopodia had diameters and lengths of approximately 200 nm and 3 um,
      respectively. Pretreatment with an IP3 receptor blocker, 2-aminoethoxydiphenyl
      borate (2-APB), prevented the senktide-induced growth in filopodia; demonstrating
      that NK3R-induced outgrowth of filopodia likely involves the release of
      intracellular calcium. Exposure of transfected CLU209 cells to senktide for 24 h
      led to further growth of filopodia and processes that extended 10-20 um. A
      mathematical model, composed of a linear and population model was developed to
      account for the dynamics of filopodia growth during a timescale of minutes. The
      results suggest that the ligand-induced activation of NK3R affects early
      developmental processes by initiating filopodia formation that are a prerequisite
      for neuritogenesis.

PMID- 25044787
TI  - Online registry for mutations in hereditary amyloidosis including nomenclature
      recommendations.
AB  - Hereditary systemic amyloidosis comprises a group of rare monogenic diseases
      inherited in an autosomal dominant fashion. It is associated with mutations in
      genes encoding eight different proteins, including transthyretin, apolipoprotein
      AI, apolipoprotein AII, lysozyme, fibrinogen A alpha-chain, cystatin C, gelsolin
      and beta-2-microglobulin. With support from the EU FP6 EURAMY project we have
      designed an online registry of genes and mutations in hereditary amyloidosis
      including their associated clinical phenotypes, with a view to having a single
      free online portal for the collection and distribution of this information. Users
      can search the registry by either mutation, phenotype or authors who have
      published or submitted mutations. It provides a submission form for reporting
      newly identified mutations. We also wanted to introduce nomenclature which
      complies with recommendations set out by Human Genome Variation Society and HUGO
      Gene Nomenclature Committee for description of new and known genetic variants. We
      hope this registry would be a useful and convenient tool for the medical and
      scientific community.

PMID- 25044786
TI  - Investigating the tradeoffs between spatial resolution and diffusion sampling for
      brain mapping with diffusion tractography: time well spent?
AB  - Interest in mapping white matter pathways in the brain has peaked with the
      recognition that altered brain connectivity may contribute to a variety of
      neurologic and psychiatric diseases. Diffusion tractography has emerged as a
      popular method for postmortem brain mapping initiatives, including the ex-vivo
      component of the human connectome project, yet it remains unclear to what extent
      computer-generated tracks fully reflect the actual underlying anatomy. Of
      particular concern is the fact that diffusion tractography results vary widely
      depending on the choice of acquisition protocol. The two major acquisition
      variables that consume scan time, spatial resolution, and diffusion sampling, can
      each have profound effects on the resulting tractography. In this analysis, we
      determined the effects of the temporal tradeoff between spatial resolution and
      diffusion sampling on tractography in the ex-vivo rhesus macaque brain, a close
      primate model for the human brain. We used the wealth of autoradiography-based
      connectivity data available for the rhesus macaque brain to assess the anatomic
      accuracy of six time-matched diffusion acquisition protocols with varying balance
      between spatial and diffusion sampling. We show that tractography results vary
      greatly, even when the subject and the total acquisition time are held constant.
      Further, we found that focusing on either spatial resolution or diffusion
      sampling at the expense of the other is counterproductive. A balanced
      consideration of both sampling domains produces the most anatomically accurate
      and consistent results.

PMID- 25044788
TI  - Mucopolysaccharidosis type II in a female patient with a reciprocal X;9
      translocation and skewed X chromosome inactivation.
AB  - Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare X-linked
      disorder caused by deficient activity of the lysosomal enzyme, iduronate-2
      sulfatase (IDS). Phenotypic expression of MPS II in female patients rarely occurs
      and may be the result of (i) structural abnormalities of the X chromosome, (ii)
      homozygosity for disease-causing mutations, or (iii) skewed X-chromosome
      inactivation, in which the normal IDS allele is preferentially inactivated and
      the abnormal IDS allele is active. We report here on a female patient with
      clinical MPS II manifestations, deficiency of IDS enzyme activity and a de novo
      balanced reciprocal X;9 translocation. As our patient has a skewed XCI pattern,
      but neither genomic IDS mutations nor abnormal IDS transcripts were detected, we
      speculate about the possible role of the chromosomal rearrangement in reducing
      the IDS translation efficiency.

PMID- 25044789
TI  - The effects of conformational constraints in the polyamine moiety of
      philanthotoxins on AMPAR inhibition.
AB  - Philanthotoxin-433 (PhTX-433) is a known potent inhibitor of ionotropic glutamate
      receptors, and analogues have been synthesised to identify more potent and
      selective antagonists. Herein we report the synthesis of four PhTXs with a
      cyclopropane moiety introduced into their polyamine chain, and their inhibition
      of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      subtype by using two-electrode voltage-clamp assays on Xenopus oocytes expressing
      the GluA1flop subunit. All analogues were found to be more potent than PhTX-343,
      with trans-cyclopropyl-PhTX-343 being the most potent (~28-fold) and cis
      cyclopropyl-PhTX-343 least potent (~4-fold). Both cis- and trans-cyclopropyl-PhTX
      444 had intermediate potency (both~12-fold). Molecular modelling indicates that a
      cyclopropane moiety confers a favourable steric constraint to the polyamine part,
      but this is compromised by a cis conformation due to enhanced intramolecular
      folding. Elongated PhTX-444 analogues alleviate this to some extent, but optimal
      positioning of the amines is not permitted.

PMID- 25044791
TI  - New thermodynamics for evaluating the surface-phase enrichment in the lower
      surface tension component.
AB  - Regarding the surface phase of liquid mixtures as a thermodynamic phase, ideal
      surface phases are designed so that at fixed bulk-phase composition, real and
      ideal surface phases have the same chemical composition and identical limiting
      slopes for the dependence of surface tension on mole fraction. Standard chemical
      potentials are introduced for surface phase components, and quasi-exact
      expressions are worked out to compute ideal surface tensions and surface-phase
      compositions of real liquid mixtures. Guidelines for choosing molecular models to
      estimate the molar surface area of pure constituents are given. Ideal and excess
      surface tensions are calculated by using literature data for aqueous ethanol
      solutions at 298 K. These results show treatment based on Butler's equations
      grossly overestimate predicted surface tensions, thus leading to lower ethanol
      content in the surface phase. These inaccuracies are ascribed to the use of molar
      surface areas in model equations that are too small. 

PMID- 25044790
TI  - In vitro and in vivo evaluation of blood coagulation activation of polyvinyl
      alcohol hydrogel plus dextran-based vascular grafts.
AB  - Polyvinyl alcohol hydrogel (PVA) is a water-soluble synthetic polymer that is
      commonly used in biomedical applications including vascular grafting. It was
      argued that the copolymerization of PVA with dextran (Dx) can result in
      improvement of blood-biomaterial interactions. The focus of this experimental
      study was to assess that interaction through an in vivo and in vitro evaluation
      of the coagulation system activation. The thrombogenicity of the copolymer was
      determined by quantification of platelet adhesion through the lactate
      dehydrogenase assay, determination of whole blood clotting time, and by
      quantification of platelet activation by flow cytometry. The thrombin
      antithrombin complex blood levels were also determined. The obtained results for
      the in vitro assays suggested a non-thrombogenic profile for PVA/Dx. Additionally
      in vivo coagulation and hematological parameters were determined in an animal
      model after PVA/Dx vascular graft implantation. For coagulation homeostasis
      assessment, the intrinsic and extrinsic pathway's activation was determined by
      measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT).
      Other markers of coagulation and inflammation activation including d-dimers,
      interleukin-6, and C-reactive protein were also assessed. The PVA/Dx copolymer
      tended to inhibit platelet adhesion/activation process and the contact activation
      process for coagulation. These results were also confirmed with the in vivo
      experiments where the measurements for APTT, interleukin-6, and C-reactive
      protein parameters were normal considering the species normal range of values.
      The response to those events is an indicator of the in vitro and in vivo
      hemocompatibility of PVA/Dx and it allows us to select this biomaterial for
      further preclinical trials in vascular reconstruction.

PMID- 25044792
TI  - Exploring the symmetry, structure, and self-assembly mechanism of a gigantic
      seven-fold symmetric {Pd84} wheel.
AB  - The symmetry, structure and formation mechanism of the structurally self
      complementary {Pd84} = [Pd84O42(PO4)42(CH3CO2)28](70-) wheel is explored. Not
      only does the symmetry give rise to a non-closest packed structure, the mechanism
      of the wheel formation is proposed to depend on the delicate balance between
      reaction conditions. We achieve the resolution of gigantic polyoxopalladate
      species through electrophoresis and size-exclusion chromatography, the latter has
      been used in conjunction with electrospray mass spectrometry to probe the
      formation of the ring, which was found to proceed by the stepwise aggregation of
      {Pd6}(-) = [Pd6O4(CH3CO2)2(PO4)3Na(6-n)H(n)](-) building blocks. Furthermore, the
      higher-order assembly of these clusters into hollow blackberry structures of
      around 50 nm has been observed using dynamic and static light scattering.

PMID- 25044793
TI  - Water O-H bond activation by gas-phase plutonium atoms: reaction mechanisms and
      ab initio molecular dynamics study.
AB  - A thorough description of the reaction mechanisms, taking into account different
      possible spin states, offers insights into the gas-phase reaction of plutonium
      atoms with water. Two possible reactions (isomerization and dehydrogenation) are
      presented. These reactions are found to be exothermic, with the best
      thermochemical conditions observed for the dehydrogenation reaction at around
      23.5 kcal mol(-1). The nature of the chemical-bonding evolution along the
      reaction pathways are investigated by employing various methods including
      electron localization function, atoms in molecules, and Mayer bond order. Total,
      partial, and overlap population density of state diagrams and analyses are also
      presented. Reaction rates at elevated temperatures (T=298-2 000 K) are calculated
      by using variational transition-state theory with one-dimensional tunneling
      effects. In dynamics simulations, only the dehydrogenation reaction is observed,
      and found to be in good agreement with experimental values.

PMID- 25044794
TI  - Silica-particle-supported zwitterionic polymer monolith for microcolumn liquid
      chromatography.
AB  - A silica-particle-supported zwitterionic polymeric monolithic column, shortened
      as supported column (S-column), was prepared by the in situ polymerization of
      methacrylic acid, ethylene dimethacrylate, and 2-(dimethylamino)ethyl
      methacrylate in the presence of a ternary porogenic solvent containing water,
      methanol, and cyclohexanol in a 250 MUm id fused-silica capillary prepacked with
      5 MUm bare silica particles. In the S-column, a thin layer of the polymers was
      formed around the silica particles in the form of nanoglobules, leaving the
      interstitial spaces between the particles free for liquid flow. The effects of
      the preparation conditions on the morphology of the monolith were investigated by
      scanning electron microscopy and backpressure measurements. The selected
      volumetric ratio of porogens, monomer concentration, polymerization time, and
      temperature are 1:1:8 (water/methanol/cyclohexanol), 25% v/v, 5 h, and 60 degrees
      C, respectively. The S-column was evaluated by comparison with its conventional
      organic counterpart in terms of morphology, mechanical stability, permeability,
      swelling-shrinking behavior, capacity, and efficiency. The results demonstrate
      that the S-column is superior to its counterpart in all the terms with the
      exception of permeability. The above merits and zwitterionic property of the S
      column were further confirmed by separate separations of four inorganic anions
      and three organic cations. 

PMID- 25044795
TI  - Postprandial cell defense system responses to meal formulations: stratification
      through gene expression profiling.
AB  - SCOPE: Cell defenses regulating homeostatic control of postprandial stress are
      influenced by interindividual variation, food composition and health status. This
      study investigates effects of food composition on individual postprandial
      responses and associations with health. METHODS AND RESULTS: Volunteers (n = 16)
      consumed four food formulations (50% unsaturated/saturated fat, with/without
      beetroot extract 10 g/100 g) on separate occasions. GeXP assay measured whole
      blood postprandial gene expression profiles of 28 cell defense markers at
      baseline and postprandial time points 1, 2, 4, 6, 24 h. Plasma markers of
      metabolic lipids, hormones, inflammatory cytokines, oxidative stress, and DNA
      damage/repair were also assessed. SIRT 1, UCP2, HO1, GSS, PTGS2, TP53, CDKN2A,
      PPIA, SOCS3, and APE1 expression profiles revealed distinct stratified subgroups
      associated with plasma HDLs, TNF-alpha and postprandial responses of SOCS3, and
      PPIA. Leptin, IL6, and DNA strand breaks revealed differing responses to fat type
      consumed. CONCLUSION: This study demonstrates postprandial immune, inflammatory,
      redox, metabolic, and DNA repair responses that are largely independent of fat
      type consumed (unsaturated/saturated) or addition of beetroot extract, in
      apparently healthy individuals. However, postprandial responses can be
      characterized by regulation of gene expression associated with markers linked to
      health status and are subject to interindividual variation that can influence
      postprandial responses.

PMID- 25044796
TI  - NetFCM: a semi-automated web-based method for flow cytometry data analysis.
AB  - Multi-parametric flow cytometry (FCM) represents an invaluable instrument to
      conduct single cell analysis and has significantly increased our understanding of
      the immune system. However, due to new techniques allowing us to measure an
      increased number of phenotypes within the immune system, FCM data analysis has
      become more complex and labor-intensive than previously. We have therefore
      developed a semi-automatic gating strategy (NetFCM) that uses clustering and
      principal component analysis (PCA) together with other statistical methods to
      mimic manual gating approaches. NetFCM is an online tool both for subset
      identification as well as for quantification of differences between samples.
      Additionally, NetFCM can classify and cluster samples based on multidimensional
      data. We tested the method using a data set of peripheral blood mononuclear cells
      collected from 23 HIV-infected individuals, which were stimulated with
      overlapping HIV Gag-p55 and CMV-pp65 peptides or medium alone (negative control).
      NetFCM clustered the virus-specific CD8+ T cells based on IFNgamma and TNF
      responses into distinct compartments. Additionally, NetFCM was capable of
      identifying HIV- and CMV-specific responses corresponding to those obtained by
      manual gating strategies. These data demonstrate that NetFCM has the potential to
      identify relevant T cell populations by mimicking classical FCM data analysis and
      reduce the subjectivity and amount of time associated with such analysis. (c)
      2014 International Society for Advancement of Cytometry. 

PMID- 25044797
TI  - Synthesis and disaggregation of asparagine repeat-containing peptides.
AB  - Of all amino acid repeats in eukaryotes, polyglutamine (polyQ) is the most
      frequent, followed by polyasparagine (polyN). Glutamine repeats are expanded in
      proteins associated with several neurodegenerative disorders. The expanded polyQ
      domain is known to induce aggregation, and it is hypothesized that aggregation is
      directly causative of pathology. Despite the widespread presence of asparagine
      repeats in invertebrate eukaryotes, polyN is curiously quite rare in vertebrates.
      Several investigators have characterized the conformational and aggregation
      properties of polyQ-containing peptides and proteins, and to a lesser extent,
      peptides containing mixed glutamine and asparagine, but to our knowledge, there
      is no detailed characterization of polyN-containing peptides. Such a comparison
      could elucidate reasons for the paucity of asparagine repeats in humans. In this
      study, we synthesized a peptide containing a 24-asparagine repeat (N24). For
      aggregation studies, it is critical to start with monomeric unaggregated peptide.
      A protocol involving dissolution in mixed trifluoroacetic acid and
      hexafluoroisopropanol (TFA + HFIP) solvents is widely used for disaggregation of
      polyQ peptides. We used the same protocol for N24 but discovered that there was
      both oxidative damage and insufficient disaggregation. Oxidation of tryptophan,
      used as a flanking residue, was common. Moreover, we found evidence of Forster
      resonance energy transfer between Trp and its oxidation product N
      formylkynurenine, even in chemical denaturants. This suggested that N24 was
      insufficiently disaggregated, a conclusion that was further supported by gel
      electrophoresis analysis. Oxidation was reduced, but not eliminated, by addition
      of methionine to the buffer. Formic acid proved to be a better disaggregator and
      caused no oxidative damage. The glutamine repeat peptide Q24 also underwent some
      oxidation after extended incubation in TFA + HFIP, but there was no evidence of
      Forster resonance energy transfer, and samples appeared monomeric by gel
      electrophoresis. This result indicates that polyN-containing peptides self
      associate more strongly than polyQ-containing peptides. Circular dichroism
      spectra reveal a greater propensity for beta-turn formation in polyN than polyQ,
      providing an explanation for the increased stability of polyN aggregates relative
      to polyQ.

PMID- 25044798
TI  - Why less is more when generating tryptic peptides in bottom-up proteomics.
AB  - Proteolytic digestion is a time consuming and critical step in bottom-up
      proteomic analysis. The most widely used protease, trypsin, has high specificity
      and generates peptides that are considered to be ideally suited for bottom-up LC
      MS technology. By exploiting key factors affecting enzymatic activity we obtained
      a simple, straightforward, and rapid in-solution digest protocol that performed
      better than the conventional overnight digestion method in terms of amino acid
      coverage of proteins, number of peptides generated, and peptide ion abundances.
      Prolonged digestion time, such as overnight digestion, leads to decline in
      protein amino acid coverage and loss of tryptic peptides. This was found to be
      caused by complete digestion by trypsin leading to an increased number of small
      peptides that are not LC-MS detectable. Slow-rate nontryptic digestion of
      peptides is a contributing factor for loss of peptide ion intensities during
      extended digestion time. Our work demonstrates that for both qualitative and
      quantitative bottom-up proteomic studies it is beneficial to prevent trypsin
      digestion to go to completion by reducing treatment time from the conventional
      several hours to a few minutes cleavage time.

PMID- 25044799
TI  - Early weight loss while on lorcaserin, diet and exercise as a predictor of week
      52 weight-loss outcomes.
AB  - OBJECTIVE: To identify an early treatment milestone that optimizes sensitivity
      and specificity for predicting >=5% weight loss at Week (W) 52 in patients with
      and without type 2 diabetes on lorcaserin or placebo. METHODS: Post hoc area
      under the curve for receiver operating characteristic analyses of data from three
      phase 3 trials comparing lifestyle modification+placebo with lifestyle
      modification+lorcaserin. A total of 6897 patients (18-65 years; BMI, 30-45 or 27
      29.9 kg/m(2) with >=1 comorbidity) were randomized to placebo or lorcaserin 10 mg
      bid. Changes (baseline to W52) in cardiometabolic parameters were assessed.
      RESULTS: Response (>=5% weight loss from baseline) at W12 was a strong predictor
      of W52 response. Lorcaserin patients with a W12 response achieved mean W52 weight
      losses of 10.6 kg (without diabetes) and 9.3 kg (with diabetes). Proportions
      achieving >=5% and >=10% weight loss at W52 were 85.5% and 49.8% (without
      diabetes), and 70.5% and 35.9% (with diabetes). Lorcaserin patients who did not
      achieve a W12 response lost 3.2 kg (without diabetes) and 2.8 kg (with diabetes)
      at W52. Responders had greater improvements in cardiometabolic risk factors than
      the modified intent-to-treat (MITT) population, consistent with greater weight
      loss. CONCLUSIONS: >=5% weight loss by W12 predicts robust response to lorcaserin
      at 1 year.

PMID- 25044801
TI  - Self-supported Cu3P nanowire arrays as an integrated high-performance three
      dimensional cathode for generating hydrogen from water.
AB  - Searching for inexpensive hydrogen evolution reaction (HER) electrocatalysts with
      high activity has attracted considerable research interest in the past years.
      Reported herein is the topotactic fabrication of self-supported Cu3 P nanowire
      arrays on commercial porous copper foam (Cu3 P NW/CF) from its Cu(OH)2 NW/CF
      precursor by a low-temperature phosphidation reaction. Remarkably, as an
      integrated three-dimensional hydrogen-evolving cathode operating in acidic
      electrolytes, Cu3 P NW/CF maintains its activity for at least 25 hours and
      exhibits an onset overpotential of 62 mV, a Tafel slope of 67 mV dec(-1) , and a
      Faradaic efficiency close to 100 %. Catalytic current density can approach 10 mA
      cm(-2) at an overpotential of 143 mV. 

PMID- 25044803
TI  - Surface hydrogenation reactions at the single-molecule level.
AB  - Hydrogenation and dehydrogenation reactions on metal surfaces are among the most
      important in heterogeneous catalysis. Such reactions can be observed and
      characterized at the single-molecule level with low temperature scanning
      tunnelling microscopy (LT-STM). A brief review of such studies is presented. A
      specific example, the hydrogenation of methyl isocyanide to methyl aminocarbyne
      on the Pt(111) surface, is described in detail. This reaction was first
      identified in a study with reflection absorption infrared spectroscopy, a
      technique that averages over monolayer quantities of molecules. The example
      illustrates the importance of characterization of surface reactions with
      complementary techniques in order to properly interpret the single-molecule LT
      STM images. A second example of the complementary nature of LT-STM and other
      surface characterization methods is the tip-induced dehydrogenation on Pt(111) of
      acetonitrile, the more stable isomer of methyl isocyanide. 

PMID- 25044800
TI  - Therapeutic applications of an expanded genetic code.
AB  - To date, over 100 noncanonical amino acids (ncAAs) have been genetically encoded
      in living cells in order to expand the functional repertoire of the canonical 20
      amino acids. More recently, this technology has been expanded to the field of
      protein therapeutics, where traditional chemical methods typically result in
      heterogeneous mixtures of proteins. The site-specific incorporation of ncAAs with
      orthogonal chemical groups allows unprecedented control over the site of
      conjugation and the stoichiometry, thus facilitating the rational optimization of
      the biological functions and/or pharmacokinetics of biologics. Herein, we discuss
      the recent contribution of ncAA technology in enhancing the pharmacological
      properties of current protein therapeutics as well as developing novel
      therapeutic modalities. 

PMID- 25044804
TI  - From waste paper basket to solid state and Li-HEC ultracapacitor electrodes: a
      value added journey for shredded office paper.
AB  - Hydrothermal processing followed by controlled pyrolysis of used white office
      paper (a globally collectable shredded paper waste) are performed to obtain high
      surface area carbon with hierarchical pore size distribution. The BET specific
      surface area of such carbon is 2341 m(2) g(-1). The interconnected macroporous
      structure along with the concurrent presence of mesopores and micropores makes
      the material ideal for ultracapacitor application. Such waste paper derived
      carbon (WPC) shows remarkable performance in all solid-state supercapacitor
      fabricated with ionic liquid-polymer gel electrolyte. At room temperature, the
      material exhibits a power density of 19,000 W kg(-1) with an energy capability of
      31 Wh kg(-1). The Li-ion electrochemical capacitor constructed using WPC as
      cathode also shows an excellent energy storage capacity of 61 Wh kg(-1).

PMID- 25044805
TI  - High-rate oxygen electroreduction over graphitic-N species exposed on 3D
      hierarchically porous nitrogen-doped carbons.
AB  - Nitrogen-doped species (NDs) are theoretically accepted as a determinant of the
      catalytic activity of metal-free N-doped carbon (NC) catalysts for oxygen
      reduction reaction (ORR). However, direct relationships between ND type and ORR
      activity have been difficult to extract because the complexity of carbon matrix
      impairs efforts to expose specific NDs. Herein, we demonstrate the fabrication of
      a 3D hierarchically porous NC catalyst with micro-, meso-, and macroporosity in
      one structure, in which sufficient exposure and availability of inner-pore
      catalytic sites can be achieved due to its super-high surface area (2191 cm(2) 
      g(-1) ) and interconnected pore system. More importantly, in-situ formation of
      graphitic-N species (GNs) on the surface of NC stimulated by KOH activation
      enables us to experimentally reveal the catalytic nature of GNs for ORR, which is
      of great significance for the design and development of advanced metal-free NC
      electrocatalysts. 

PMID- 25044806
TI  - Greenhouse gas emissions from dairy manure management: a review of field-based
      studies.
AB  - Livestock manure management accounts for almost 10% of greenhouse gas emissions
      from agriculture globally, and contributes an equal proportion to the US methane
      emission inventory. Current emissions inventories use emissions factors
      determined from small-scale laboratory experiments that have not been compared to
      field-scale measurements. We compiled published data on field-scale measurements
      of greenhouse gas emissions from working and research dairies and compared these
      to rates predicted by the IPCC Tier 2 modeling approach. Anaerobic lagoons were
      the largest source of methane (368 +/- 193 kg CH4 hd(-1) yr(-1)), more than three
      times that from enteric fermentation (~120 kg CH4 hd(-1) yr(-1)). Corrals and
      solid manure piles were large sources of nitrous oxide (1.5 +/- 0.8 and 1.1 +/-
      0.7 kg N2O hd(-1) yr(-1), respectively). Nitrous oxide emissions from anaerobic
      lagoons (0.9 +/- 0.5 kg N2O hd(-1) yr(-1)) and barns (10 +/- 6 kg N2O hd(-1) yr(
      1)) were unexpectedly large. Modeled methane emissions underestimated field
      measurement means for most manure management practices. Modeled nitrous oxide
      emissions underestimated field measurement means for anaerobic lagoons and manure
      piles, but overestimated emissions from slurry storage. Revised emissions factors
      nearly doubled slurry CH4 emissions for Europe and increased N2O emissions from
      solid piles and lagoons in the United States by an order of magnitude. Our
      results suggest that current greenhouse gas emission factors generally
      underestimate emissions from dairy manure and highlight liquid manure systems as
      promising target areas for greenhouse gas mitigation.

PMID- 25044807
TI  - Diabetes Metabolism: Research and Reviews--Chinese Diabetes Society special
      issue: a small but encouraging step toward the successful control of diabetes in
      China.
AB  - It is now recognised that nearly one third of all people with diabetes worldwide
      are Chinese and that this disease is the third leading cause of death in China.
      In this special issue of the journal we publish articles covering a number of
      clinical and experimental studies of diabetes as well as metabolic diseases in
      China with the aim of helping the readers to better understand the overall
      picture of this disease in China. 

PMID- 25044808
TI  - Methodological strategies for transgene copy number quantification in goats
      (Capra hircus) using real-time PCR.
AB  - Taking into account the importance of goats as transgenic models, as well as the
      rarity of copy number (CN) studies in farm animals, the present work aimed to
      evaluate methodological strategies for accurate and precise transgene CN
      quantification in goats using quantitative polymerase chain reaction (qPCR).
      Mouse and goat lines transgenic for human granulocyte-colony stimulating factor
      were used. After selecting the best genomic DNA extraction method to be applied
      in mouse and goat samples, intra-assay variations, accuracy and precision of CN
      quantifications were assessed. The optimized conditions were submitted to
      mathematical strategies and used to quantify CN in goat lines. The findings were
      as follows: validation of qPCR conditions is required, and amplification
      efficiency is the most important. Absolute and relative quantifications are able
      to produce similar results. For normalized absolute quantification, the same
      plasmid fragment used to generate goat lines must be mixed with wild-type goat
      genomic DNA, allowing the choice of an endogenous reference gene for data
      normalization. For relative quantifications, a resin-based genomic DNA extraction
      method is strongly recommended when using mouse tail tips as calibrators to avoid
      tissue-specific inhibitors. Efficient qPCR amplifications (>=95%) allow reliable
      CN measurements with SYBR technology. TaqMan must be used with caution in goats
      if the nucleotide sequence of the endogenous reference gene is not yet well
      understood. Adhering to these general guidelines can result in more exact CN
      determination in goats. Even when working under nonoptimal circumstances, if
      assays are performed that respect the minimum qPCR requirements, good estimations
      of transgene CN can be achieved.

PMID- 25044809
TI  - Biosourced polymetallic catalysts: an efficient means to synthesize
      underexploited platform molecules from carbohydrates.
AB  - Polymetallic hyperaccumulating plants growing on wastes from former mining
      activity were used as the starting material in the preparation of novel plant
      based Lewis acid catalysts. The preparation of biosourced Lewis acid catalysts is
      a new way to make use of mining wastes. These catalysts were characterized by X
      ray fluorescence, X-ray diffraction, inductively coupled plasma mass
      spectrometry, and direct infusion electrospray ionization mass spectrometry.
      These analyses revealed a complex composition of metal species, present mainly as
      polymetallic chlorides. The catalysts proved to be efficient and recyclable in a
      solid-state version of the Garcia Gonzalez reaction, which has been
      underexploited until now in efforts to use carbohydrates from biomass. This
      methodology was extended to various carbohydrates to obtain the corresponding
      polyhydroxyalkyl furans in 38-98% yield. These plant-based catalysts may be a
      better alternative to classical Lewis acid catalysts that were previously used
      for the Garcia Gonzalez reaction, such as ZnCl2 , FeCl3 , and CeCl3 , which are
      often unrecyclable, require aqueous treatments, or rely on metals, the current
      known reserves of which will be consumed in the coming decades. Moreover, the
      plant-based catalysts allowed novel control of the Garcia Gonzalez reaction, as
      two different products were obtained depending on the reaction conditions.

PMID- 25044810
TI  - Use of percutaneous image-guided coaxial core-needle biopsy for diagnosis of
      intraabdominal lymphoma.
AB  - Although pathological diagnosis is essential for managing malignant lymphoma,
      intraabdominal lesions are generally difficult to approach due to the
      invasiveness of abdominal surgery. Here, we report the use of percutaneous image
      guided coaxial core-needle biopsy (CNB) to obtain intraabdominal specimens for
      diagnosing intraabdominal lymphomas, which typically requires histopathological
      and immunohistochemical evaluation. We retrospectively reviewed consecutive cases
      involving computed tomography (CT)- or ultrasonography (US)-guided CNB to obtain
      pathological specimens for intraabdominal lesions from 1999 to 2011. Liver,
      spleen, kidney, and inguinal node biopsies were excluded. We compared CNBs with
      laparotomic biopsies. A total of 66 CNBs were performed for 59 patients (32
      males, 27 females; median age, 63.5), including second or third repeat
      procedures. Overall diagnostic rate was 88.5%. None of the patients required
      additional surgical biopsies. Notably, the median interval between recognition of
      an intraabdominal mass and biopsy was only 1 day. Forty-five procedures were
      performed for hematological malignancies. Adequate specimens were obtained for
      histopathological diagnosis in 86% of cases. Flow cytometry detected lymphoma
      cells in 79.5% of cases. Twelve patients (nine males, three females; median age,
      60) were eligible for surgical biopsy. While every postoperative course was
      satisfactory, median duration from lesion recognition to therapy initiation for
      lymphoma cases was significantly shorter for CNB than for surgical biopsy (14 vs.
      35 days). While one-fourth of the patients were not eligible for the procedures,
      CNB is safe and highly effective for diagnosis of intraabdominal lymphomas. This
      method significantly improves sampling and potentially helps attain
      immunohistological distinction, allowing for more timely therapy initiation. 

PMID- 25044811
TI  - Diffusion tensor imaging assesses triceps surae dysfunction after achilles
      tenotomy in rats.
AB  - PURPOSE: To elucidate the relationship of diffusion tensor imaging (DTI) with
      structural changes and muscle function in skeletal muscle. MATERIALS AND METHODS:
      The subjects were 21 12-week-old male rats. Achilles tenotomy was performed on
      the right legs. Proton density-weighted images and DTI (7.04T) of the triceps
      surae at 2 and 4 weeks posttenotomy were obtained. Eigenvalues (lambda) and
      fractional anisotropy (FA) were calculated from the muscle images. After imaging,
      histological specimens of the triceps surae were prepared. The long axis and
      cross-sectional area of the triceps surae were measured 2 and 4 weeks
      postoperatively. The strength of ankle plantar flexion was measured. Correlations
      of DTI parameters with morphological values and muscle strength were analyzed.
      RESULTS: lambda1 declined after tenotomy (P < 0.01), and lambda2 and lambda3
      declined at 4 weeks posttenotomy (P < 0.01). FA increased at 4 weeks posttenotomy
      (P < 0.01). Atrophy of the triceps surae was observed in the tissues images of
      the treatment group. The muscle belly significantly shortened postoperatively,
      and a decline in plantar flexion force was observed after tenotomy. Positive
      correlations were observed between lambda1 and muscle strength (r = 0.89) and
      between lambda1 and the length of the long axis of the muscle belly (r = 0.81).
      CONCLUSION: DTI may serve as a marker of muscle function.

PMID- 25044812
TI  - Abstracts of the ILTS 20(th) Annual International Congress, June 3-7, 2014,
      London, United Kingdom.

PMID- 25044813
TI  - Combining the best of two worlds: nanoparticles and nanofibers.
AB  - The preparation and applications of nanoparticles and nanofibers are widely
      described in the literature. Both types of materials have specific advantages but
      also drawbacks. We discuss here the methods to fabricate nanofibers from
      nanoparticles and vice versa by template-free methods and colloid
      electrospinning. Nanoparticles and nanofibers can be also synergistically
      combined to yield nanostructured constructs that display highly advantageous
      properties such as good mechanical integrity, double protection of encapsulated
      substances, or the possibility to co-encapsulate payloads with different
      polarities. 

PMID- 25044814
TI  - Efficient oxidation and destabilization of Zn(Cys)4 zinc fingers by singlet
      oxygen.
AB  - Singlet oxygen ((1)O2) plays an important role in oxidative stress in all types
      of organisms, most of them being able to mount a defense against this oxidant.
      Recently, zinc finger proteins have been proposed to be involved in its cellular
      detection but the molecular basis of this process still remains unknown. We have
      studied the reactivity of a Zn(Cys)4 zinc finger with (1)O2 by combinations of
      spectroscopic and analytical techniques, focusing on the products formed and the
      kinetics of the reaction. We report that the cysteines of this zinc finger are
      oxidized to sulfinates by (1)O2. The reaction of the ZnS4 core with (1)O2 is very
      fast and efficient with almost no physical quenching of (1)O2. A drastic (ca.
      five orders of magnitude) decrease of the Zn(2+) binding constant was observed
      upon oxidation. This suggests that the Zn(Cys)4 zinc finger proteins would
      release their Zn(2+) ion and unfold upon reaction with (1)O2 under cellular
      conditions and that zinc finger sites are likely targets for (1)O2.

PMID- 25044815
TI  - N-heterocyclic-carbene-catalyzed synthesis of 2-aryl indoles.
AB  - A convergent and efficient transition-metal-free catalytic synthesis of 2-aryl
      indoles has been developed. The interception of a highly reactive and transient
      aza-ortho-quinone methide by an acyl anion equivalent generated through N
      hetereocyclic carbene catalysis is central to this successful strategy. High
      yields and a wide scope as well as the streamlined synthesis of a kinase
      inhibitor are reported. 

PMID- 25044816
TI  - Repeated stimulation of dopamine D1-like receptor and hyperactivation of mTOR
      signaling lead to generalized seizures, altered dentate gyrus plasticity, and
      memory deficits.
AB  - The acute activation of the dopamine D1-like receptors (D1R) is involved in a
      plethora of functions ranging from increased locomotor activity to the
      facilitation of consolidation, storage, and retrieval of memories. Although much
      less characterized, epileptiform activities, usually triggered by disruption of
      the glutamate and GABA balance, have also been reported to involve the
      dopaminergic transmission. Using a combination of biochemical,
      immunohistochemical, electrophysiological, and behavioral approaches we have
      investigated the consequences of repeated stimulation of D1R using the selective
      D1R-like agonist SKF81297. Here, we report that repeated systemic administration
      of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the
      hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted
      long-term potentiation (LTP) in the dentate gyrus (DG) and altered recognition
      memories. The mTOR inhibitor rapamycin delays the development of SKF81297-induced
      kindled seizures, and rescues LTP in the DG and object recognition. Our results
      show that repeated stimulation of D1R is sufficient to induce generalized
      seizures leading to the overactivation of mTOR signaling, disrupted hippocampal
      plasticity, and impaired long-term recognition memories. This work highlights the
      interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and
      cognitive deficits.

PMID- 25044817
TI  - Chemocatalytic upgrading of tailored fermentation products toward biodiesel.
AB  - Biological and chemocatalytic processes are tailored in order to maximize the
      production of sustainable biodiesel from lignocellulosic sugar. Thus, the
      combination of hydrotalcite-supported copper(II) and palladium(0) catalysts with
      a modification of the fermentation from acetone-butanol-ethanol to isopropanol
      butanol-ethanol predictably produces higher concentrations of diesel-range
      components in the alkylation reaction. 

PMID- 25044818
TI  - Association of gestational diabetes and breastfeeding on obesity prevalence in
      predominately Hispanic low-income youth.
AB  - OBJECTIVE: The goal of this study was to examine if breastfeeding duration by
      gestational diabetes mellitus status impacted the prevalence of obesity in
      offspring. METHODS: Data were obtained from a 2011 phone survey with caregivers
      of low-income children (2-4 years) participating in the Women, Infants and
      Children programme in Los Angeles County. The final sample included 2295
      children, 84% Hispanic and 48% female. Chi-square and binary logistic regression
      were used to assess gestational diabetes status and breastfeeding duration on the
      prevalence of obesity, with the following a priori covariates: child's ethnicity,
      birth weight, age in months and sex. RESULTS: Breastfeeding and gestational
      diabetes were significantly associated with obesity prevalence (P < 0.01). Using
      gestational diabetes mellitus and no breastfeeding as the referent category,
      gestational diabetes mellitus offspring who were breastfed >=12 months had a 72%
      decrease in obesity prevalence (adjusted odds ratio = 0.28, confidence interval
      0.89-0.03, P = 0.05). CONCLUSIONS: These findings suggest that > 12 months of
      breastfeeding duration in the gestational diabetes mellitus group and any
      duration of breastfeeding in the non-gestational diabetes mellitus mothers is
      needed to reduce obesity levels in a primarily Hispanic population.

PMID- 25044819
TI  - Reducing the psychological distress of family caregivers of home based palliative
      care patients: longer term effects from a randomised controlled trial.
AB  - BACKGROUND: Palliative care incorporates comprehensive support of family
      caregivers because many of them experience burden and distress. However, evidence
      based support initiatives are few. PURPOSE: We evaluated a one-to-one
      psychoeducational intervention aimed at mitigating the distress of caregivers of
      patients with advanced cancer receiving home-based palliative care. We
      hypothesised that caregivers would report decreased distress as assessed by the
      General Health Questionnaire (GHQ). METHOD: A randomised controlled trial
      comparing two versions of the delivery of the intervention (one face-to-face home
      visit plus telephone calls versus two visits) plus standard care to a control
      group (standard care only) across four sites in Australia. RESULTS: Recruitment
      to the one visit condition was 57, the two visit condition 93, and the control
      148. We previously reported non-significant changes in distress between times 1
      (baseline) and 2 (1-week post-intervention) but significant gains in competence
      and preparedness. We report here changes in distress between times 1 and 3 (8
      week post-death). There was significantly less worsening in distress between
      times 1 and 3 in the one visit intervention group than in the control group;
      however, no significant difference was found between the two visit intervention
      and the control group. CONCLUSIONS: These results are consistent with the aim of
      the intervention, and they support existing evidence demonstrating that
      relatively short psychoeducational interventions can help family caregivers who
      are supporting a dying relative. The sustained benefit during the bereavement
      period may also have positive resource implications, which should be the subject
      of future inquiry.

PMID- 25044820
TI  - A Pap test does not screen for everything: nurse practitioner knowledge of
      ovarian cancer.
AB  - PURPOSE: Nurse practitioners (NPs) are in a prime position to educate women about
      initial signs and symptoms of ovarian cancer (OC) and perform appropriate
      screening tests. However, little is known about NPs knowledge regarding OC. This
      article's purpose is to present the outcomes of a focused OC awareness program
      for NP students. DATA SOURCES: NP students (N = 104) participated in this
      longitudinal one group pre-post study. Knowledge was calculated based on the
      number of correct answers for a total knowledge score and subscales related to OC
      incidence, risk, screening, symptoms, and treatment. An item related to the
      effectiveness of the Pap test to screen for OC was evaluated separately.
      CONCLUSION: Knowledge deficits continue to exist related to OC, emphasizing the
      need for NPs to be aware of risk factors, symptoms, and early detection options
      for women with average risk. Many NP students erroneously believed a Pap test was
      an effective screening tool for OC. IMPLICATIONS FOR PRACTICE: Many NPs are
      inadequately prepared to assess risk, detect early symptoms, and perform
      screening tests for OC. Continuing education and reinforcement about OC is
      essential if NPs are to provide appropriate education to clients and detect this
      deadly disease as early as possible.

PMID- 25044822
TI  - Fair share? Journal editors, researchers, and others grapple over whether
      research and clinical data should be shared.

PMID- 25044821
TI  - Practical aerobic oxidations of alcohols and amines with homogeneous copper/TEMPO
      and related catalyst systems.
AB  - Oxidations of alcohols and amines are common reactions in the synthesis of
      organic molecules in the laboratory and industry. Aerobic oxidation methods have
      long been sought for these transformations, but few practical methods exist that
      offer advantages over traditional oxidation methods. Recently developed
      homogeneous Cu/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidinyl-N-oxyl) and related
      catalyst systems appear to fill this void. The reactions exhibit high levels of
      chemoselectivity and broad functional-group tolerance, and they often operate
      efficiently at room temperature with ambient air as the oxidant. These advances,
      together with their historical context and recent applications, are highlighted
      in this Minireview.

PMID- 25044826
TI  - Parameters affecting efficiency of in ovo electroporation of the avian neural
      tube and crest.
AB  - BACKGROUND: Many variations in avian in ovo transfection of the neural tube/crest
      have been reported, but never compared quantitatively. RESULTS: Genome
      integrating pT2K-CAGGS-GFP and pCAGGS-T2TP transposase plasmids were co
      electroporated into quail E2 embryo trunk neural tube and the proportion of GFP
      expressing neural cells was counted 1 and 7 days later. Electroporation
      efficiency increased with plasmid concentration and pulse number but plateaued
      at, respectively, above 1.25 ug/uL and 3 pulses. Bilateral electroporation
      transfected more cells than unilateral but less than that anticipated by doubling
      the unilateral treatment. Holding the concentration of GFP plasmid constant and
      varying the transposase plasmid concentration revealed an optimum ratio of, in
      this case, 4:1 (1.2 ug/uL:0.3 ug/uL). Leaving transfected embryos to E9 confirmed
      that expression was maintained in vivo with the transposase system, but declined
      with non-integrated plasmid. Transfection of neural crest cells was low if
      electroporated less than 6-8 hr before emigration. We propose this indicates loss
      of epithelial integrity well prior to exit. We suggest this event be termed
      epithelio-mesenchymal transition sensu stricto, whereas the term delamination be
      reserved for the later emigration from the neural epithelium. CONCLUSIONS: Co
      electroporation in ovo must take into account plasmid(s) concentration and ratio,
      pulse number, pulse directionality, and timing.

PMID- 25044827
TI  - Flagellin modulates TIM4 expression in mast cells.
AB  - T-helper (Th) 2 polarization functions in a number of immune diseases, but their
      pathogenesis needs further investigation. Some microbial products or components
      are strong adjuvants in the creation of mouse models of Th2 polarization. T cell
      immunoglobulin mucin molecule (TIM) 4 is a facilitator in the initiation of Th2
      response. This study looks at the role of one of the microbial products,
      flagellin (FGN), in the induction of TIM4 expression in mast cells. Bone marrow
      derived mast cells (BMMC) were generated. Induction of TIM4 in mast cells was
      assessed in both experiments in vitro and in vivo. The signal transducer and
      activator of transcription 6 (Stat6) phosphorylation in BMMC were assessed by
      Western blotting. A coculture model with FGN-primed BMMC and naive CD4(+) T cells
      was employed to assess FGN in facilitating the expression of TIM4 in mast cells.
      After exposure to FGN, TIM4 levels were significantly increased in BMMC and mast
      cells of the mouse intestine, which was accompanied by increased STAT6
      phosphorylation. Culture with FGN-primed BMMC, naive CD4(+) T cells developed
      into Th2 cells by a TIM4-dependent manner. We conclude that FGN can induce mast
      cells to express TIM4, which helps initiate Th2 polarization. 

PMID- 25044828
TI  - Planum temporale asymmetry in developmental dyslexia: Revisiting an old question.
AB  - Among the various asymmetrical structures of the human brain, the planum
      temporale, an anatomical region associated with a variety of auditory and
      language-related processes, has received particular attention. While its surface
      area has been shown to be greater in the left hemisphere compared to the right in
      about two-thirds of the general population, altered patterns of asymmetry were
      revealed by post mortem analyses in individuals with developmental dyslexia.
      These findings have been inconsistently replicated in magnetic resonance imaging
      studies of this disorder. In this report, we attempt to resolve past
      inconsistencies by analyzing the T1-weighted MR images of 81 children (mean age:
      11 years, sd: 17 months), including 46 control (25 boys) and 35 dyslexic children
      (20 boys). We manually outlined Heschl's gyri, the planum temporale and the
      posterior rami of the Sylvian fissure on participants' brain images, using the
      same anatomical criteria as in post mortem studies. Results revealed an altered
      pattern of asymmetry of the planum temporale surface area in dyslexic boys only,
      with a greater proportion of rightward asymmetrical cases among dyslexic boys
      compared to control boys. Additionally, analyses of cortical thickness showed no
      asymmetry differences between groups for any of the regions of interest. Finally,
      a greater number of Heschl's gyrus full duplications emerged for the right
      hemisphere of dyslexic boys compared to controls. The present findings confirm
      and extend early post mortem observations. They also stress the importance of
      taking gender into account in studies of developmental dyslexia.

PMID- 25044829
TI  - Decabrominated diphenyl ether and methylmercury impair fetal nervous system
      development in mice at documented human exposure levels.
AB  - The central nervous system (CNS) is extremely vulnerable to the toxic effects of
      environmental pollutants during development. Polybrominated diphenyl ethers
      (PBDEs) are persistent contaminants, increasingly present in the environment and
      in human tissues. Recent investigations identified a correlation between maternal
      exposure to PBDEs and impairment in fetal neurobehavioral development, suggesting
      that these contaminants pose a potential risk for children. We investigated on
      the potential effects of environmental decabrominated diphenyl ether (decaBDE,
      the fully brominated congener) on key neurodevelopmental molecules (e.g.,
      synaptic proteins and immature neuron markers) in fetal mouse neurons.
      Methylmercury was used as reference neurotoxic contaminant and to evaluate its
      possible synergism with decaBDE. The neurotoxic effects of decaBDE and
      methylmercury were determined in developing cultured neurons from mouse fetal
      hippocampus and cerebellum. Neuron death, dendritic branching, synaptic protein
      expression, markers of immature neurons, and microglia activation were evaluated
      by immunocytochemistry. Brain samples from prenatally treated embryos were also
      examined for neurotoxicity signs by immunoblotting and histochemistry. DecaBDE
      significantly affected (down to 0.4 nM) the number of dendritic branches, and the
      levels of synaptic proteins and doublecortin in cultured neurons. Prenatal
      exposure to decaBDE decreased the synaptic proteins and increased the expression
      of the immature neuron and microglial markers in mouse fetuses. In conclusion,
      prenatal exposure to realistic (relevant for human exposure) concentrations of
      decaBDE induces impairment of fetal CNS development in mice, suggesting a
      potential risk of fetotoxicity in humans.

PMID- 25044830
TI  - Evidence against RAB40AL being the locus for Martin-Probst X-linked deafness
      intellectual disability syndrome.
AB  - RAB40AL has been reported as the locus for Martin-Probst syndrome (MPS), an X
      linked deafness-intellectual disability syndrome. The report was based on
      segregation of a missense change p.D59G with the disease in a single family and
      in vitro localization studies. We found the p.D59G variant by whole-exome
      sequencing in two patients; however, the diagnosis of MPS was excluded in both
      cases. Furthermore, screening of control DNA samples (n = 810) from a general
      Polish population, using allele-specific PCR and direct DNA sequencing for
      verification, identified p.D59G in 8/405 males and 12/405 females. High
      prevalence of the p.D59G variant (2.47%) is typical for a common genetic
      variation observed in asymptomatic individuals. Our data question the role of
      RAB40AL mutation as a disease-causing change and the involvement of RAB40AL in
      MPS. Considering an increasing use of next-generation sequencing in the clinical
      setting, our finding is of practical diagnostic importance.

PMID- 25044831
TI  - Eight years experience from a skeletal dysplasia referral center in a tertiary
      hospital in Southern India: a model for the diagnosis and treatment of rare
      diseases in a developing country.
AB  - We report on a series of 514 consecutive diagnoses of skeletal dysplasia made
      over an 8-year period at a tertiary hospital in Kerala, India. The most common
      diagnostic groups were dysostosis multiplex group (n = 73) followed by FGFR3 (n =
      49) and osteogenesis imperfecta and decreased bone density group (n = 41).
      Molecular confirmation was obtained in 109 cases. Clinical and radiographic
      evaluation was obtained in close diagnostic collaboration with expert groups
      abroad through Internet communication for difficult cases. This has allowed for
      targeted biochemical and molecular studies leading to the correct identification
      of rare or novel conditions, which has not only helped affected families by
      allowing for improved genetic counseling and prenatal diagnosis but also resulted
      in several scientific contributions. We conclude that (1) the spectrum of genetic
      bone disease in Kerala, India, is similar to that of other parts of the world,
      but recessive entities may be more frequent because of widespread consanguinity;
      (2) prenatal detection of skeletal dysplasias remains relatively rare because of
      limited access to expert prenatal ultrasound facilities; (3) because of the low
      accessibility to molecular tests, precise clinical-radiographic phenotyping
      remains the mainstay of diagnosis and counseling and of gatekeeping to efficient
      laboratory testing; (4) good phenotyping allows, a significant contribution to
      the recognition and characterization of novel entities. We suggest that the tight
      collaboration between a local reference center with dedicated personnel and
      expert diagnostic networks may be a proficient model to bring current diagnostics
      to developing countries.

PMID- 25044832
TI  - Exploring directional invasion of serum nuclease into siRNA duplexes by
      asymmetrical terminal modifications.
AB  - In this study we demonstrated that ribonuclease A (RNase A) can recognize the
      thermodynamic asymmetry of siRNA duplexes, similar to other proteins involved in
      siRNA function such as argonaute 2. RNase A preferentially invades the siRNA
      duplex through the less stable terminus, i.e., the 3' terminus of the sense
      strand. As evidence, only phosphorothioate (PS) modification at the sense strand
      overhang improved serum stability, whereas PS modification at the antisense
      strand overhang did not affect stability. Moreover, the improvement in stability
      caused by modification at the sense strand overhang was found to correlate with
      the terminal base pair composition of the siRNA. Gel electrophoresis and MALDI
      TOF MS analysis indicated that modifications at the sense strand overhang
      improved the serum stability of siRNAs by inhibiting the directional invasion of
      RNase A. The blocking effect was not brought about by stabilization of the siRNA
      duplexes because there was no clear difference between the melting temperatures
      of siRNAs with PS modifications at each 3' overhang.

PMID- 25044833
TI  - Simultaneous assessment of kinetic, site-specific, and structural aspects of
      enzymatic protein phosphorylation.
AB  - Protein phosphorylation is a widespread process forming the mechanistic basis of
      cellular signaling. Up to now, different aspects, for example, site-specificity,
      kinetics, role of co-factors, and structure-function relationships have been
      typically investigated by multiple techniques that are incompatible with one
      another. The approach introduced here maximizes the amount of information gained
      on protein (complex) phosphorylation while minimizing sample handling. Using high
      resolution native mass spectrometry on intact protein (assemblies) up to 150 kDa
      we track the sequential incorporation of phosphate groups and map their
      localization by peptide LC-MS/MS. On two model systems, the protein kinase G and
      the interplay between Aurora kinase A and Bora, we demonstrate the simultaneous
      monitoring of various aspects of the phosphorylation process, namely the effect
      of different cofactors on PKG autophosphorylation and the interaction of AurA and
      Bora as both an enzyme-substrate pair and physical binding partners. 

PMID- 25044834
TI  - Artificial iono- and photosensitive membranes based on an amphiphilic aza-crown
      substituted hemicyanine.
AB  - Artificial iono- and photosensitive membranes based on an amphiphilic aza-crown
      substituted hemicyanine are assembled on liquid and solid supports and their
      aggregation behaviour, which is influenced by the binding of metal cations and
      surface density, is studied. The photoinduced charge-transfer properties of an
      analogous non-amphiphilic hemicyanine in solution are also demonstrated. An
      asymmetric sandwich dimer model is proposed and existence of such dimers in
      solution is evidenced by transient absorption and fluorescence anisotropy
      experiments. Changes in absorption and emission spectra, as well as compression
      isotherms of the amphiphile observed in the presence of cations, are discussed in
      terms of 2D molecular reorganisation. Surface-pressure-controlled reversible
      excimer formation at the air-water interphase and excimer-type emission of
      Langmuir-Blodgett films in the presence of cations are demonstrated and are
      discussed on the basis of fibre-optic fluorimetry and fluorescence microscopy
      results. 

PMID- 25044835
TI  - Development of hybrid scaffolds using ceramic and hydrogel for articular
      cartilage tissue regeneration.
AB  - The regeneration of articular cartilage consisting of hyaline cartilage and
      hydrogel scaffolds has been generally used in tissue engineering. However,
      success in in vivo studies has been rarely reported. The hydrogel scaffolds
      implanted into articular cartilage defects are mechanically unstable and it is
      difficult for them to integrate with the surrounding native cartilage tissue.
      Therefore, it is needed to regenerate cartilage and bone tissue simultaneously.
      We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and
      with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were
      press-fitted into osteochondral tissue defects in a rabbit knee joints and the
      cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds
      was compared. In 12th week after implantation, the histological and
      immunohistochemical analyses were conducted to evaluate the cartilage tissue
      regeneration. In the blank and hydrogel scaffold groups, the defects were filled
      with fibrous tissues and the implanted hydrogel scaffolds could not maintain
      their initial position; in the hybrid scaffold group, newly generated cartilage
      tissues were morphologically similar to native cartilage tissues and were
      smoothly connected to the surrounding native tissues. This study demonstrates
      hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical
      stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the
      defect site.

PMID- 25044836
TI  - Gas-phase interactions between lead(II) ions and cytosine: tandem mass
      spectrometry and infrared multiple-photon dissociation spectroscopy study.
AB  - Gas-phase interactions between Pb(2+) ions and cytosine (C) were studied by
      combining tandem mass spectrometry, infrared multiple photon dissociation
      spectroscopy, and density functional theory (DFT) calculations. Both singly and
      doubly charged complexes were generated by electrospray. The [Pb(C)-H](+) complex
      was extensively studied, and this study shows that two structures, involving the
      interaction of the metal with the deprotonated canonical keto-amino tautomer of
      cytosine, are generated in the gas phase; the prominent structure is the
      bidentate form involving both the N1 and O2 electronegative centers. The DFT
      study also points out a significant charge transfer from the nucleobase to the
      low-lying p orbitals of the metal and a strong polarization of the base upon
      complexation. The various potential energy surfaces explored to account for the
      fragmentation observed are consistent with the high abundance of the [PbNH2](+)
      fragment ion.

PMID- 25044838
TI  - Particle formation by infrared laser ablation of MALDI matrix compounds.
AB  - The concentration and size distribution of particles ablated from the infrared
      matrix-assisted laser desorption/ionization matrix compounds succinic acid
      (butanedioic acid), alpha-cyano-4-hydroxycinnamic acid, and glycerol were
      measured using an aerodynamic particle sizer combined with a scanning mobility
      particle sizer. The two sizing instruments together had a sizing range to from 10
      nm to 20 um. Thin layers of the matrix compounds were irradiated with fluences
      between 6.0 and 9.5 kJ/m(2) and wavelengths between 2.8 and 3.0 um. The
      distribution of particles was characterized by a large concentration of clusters
      in the 20-nm-diameter range and large component of mass in the range of coarse
      particle with diameters greater than 1 um. The wavelength dependence revealed a
      blue shift for the maximum particle production that is attributed to heating and
      disruption of the hydrogen bonds in the matrix that shifts the absorption to
      shorter wavelengths. This blue shift has been observed previously in infrared
      matrix-assisted laser desorption/ionization.

PMID- 25044837
TI  - Membrane expression of NK receptors CD160 and CD158k contributes to delineate a
      unique CD4+ T-lymphocyte subset in normal and mycosis fungoides skin.
AB  - CD160 is a GPI-anchored Ig-like receptor identified by the BY55 mAb on human
      circulating CD56dim+ NK cells and TCRgammadelta lymphocytes. In addition, while
      most intestinal T lymphocytes express it, only a minor circulating CD4+ or CD8+ T
      lymphocyte subset is CD160+. Here we describe a population of CD4+ CD160+ human
      blood T lymphocytes of circulating cutaneous T cells. These rare T lymphocytes
      represent 2.1 +/- 1.9% of the circulating CD3+ CD4+ T cells, coexpress
      CD8alphaalpha, CD244, and perforin but lack CD28 expression, a phenotype
      corresponding to effector memory cytotoxic T-lymphocytes. Functional studies
      further confirmed their cytotoxic potential. These cells lack alphaEbeta7
      integrin and CCR7 expression but do express skin-addressing molecules CLA, and
      CCR4. In normal human skin, CD4+ CD160+ cells represent 34.6 +/- 14.7% of the
      CD4+ T lymphocytes extracted by collagenase treatment. These T cells coexpress
      CLA (81 +/- 13.6%), CCR4 (62.3 +/- 15.9%), and some CD8alphaalpha (19.6 +/- 13%)
      or CCR7 (24.4 +/- 11.7%) expression. Cutaneous T-cell lymphoma cells express the
      natural killer receptor KIR3DL2 (CD158k) used as a tumor marker. Not only we
      confirmed the expression of this marker in the blood and/or skin of mycosis
      fungoides patients but we also show for the first time CD158k expression (often
      associated with CD160) on cutaneous CD4+ T cells from healthy individuals (25.3
      +/- 15%). Therefore, CD4+ CD160+ T cells expressing CD158k might represent
      specialized cutaneous lymphocytes devoted to immune surveillance, from which
      could originate cutaneous T-cell lymphomas such as mycosis fungoides.

PMID- 25044839
TI  - Determination of conditional stability constants for some divalent transition
      metal ion-EDTA complexes by electrospray ionization mass spectrometry.
AB  - Conditional stability constants of coordination complexes comprising divalent
      transition metals, Cu(2+), Ni(2+), Zn(2+), Co(2+), and ethylenediaminetetraacetic
      acid (EDTA) were determined utilizing electrospray ionization mass spectrometry.
      The deviation of signal response of a reference complex was monitored at addition
      of a second metal ion. The conditional stability constant for the competing metal
      was then determined through solution equilibria equations. The method showed to
      be applicable to a system where Co(2+) and Zn(2+) competed for EDTA at pH 5. When
      Cu(2+) and Ni(2+) competed for EDTA, the equilibrium changed over time. This
      change was shown to be affected in rate and size by the type of organic solvent
      added. In this work, 30% of either methanol or acetonitrile was used. It was
      found that if calibration curves are prepared for both metal complexes in
      solution and the measurements are repeated with sufficient time space, any change
      in equilibrium of sample solutions will be discovered.

PMID- 25044840
TI  - New covalent modifications of phosphatidylethanolamine by alkanals: mass
      spectrometry based structural characterization and biological effects.
AB  - The pathophysiology of numerous human disorders, such as atherosclerosis,
      diabetes, obesity and Alzheimer's disease, is accompanied by increased production
      of reactive oxygen species (ROS). ROS can oxidatively damage nearly all
      biomolecules, including lipids, proteins and nucleic acids. In particular,
      (poly)unsaturated fatty acids within the phospholipid (PL) structure are easily
      oxidized by ROS to lipid peroxidation products (LPP) carrying reactive carbonyl
      groups. Carbonylated LPP are characterized by high in vivo toxicity due to their
      reactivity with nucleophilic substrates (Lys-, Cys-and His-residues in proteins
      or amino groups of phosphatidylethanolamines [PE]). Adducts of unsaturated LPP
      with PE amino groups have been reported before, whereas less is known about the
      reactivity of saturated alkanals - which are significantly increased in vivo
      under oxidative stress conditions - towards nucleophilic groups of PLs. Here, we
      present a study of new alkanal-dipalmitoyl-phosphatidylethanolamine (DPPE)
      adducts by MS-based approaches, using consecutive fragmentation (MS(n)) and
      multiple reaction monitoring techniques. At least eight different DPPE-hexanal
      adducts were identified, including Schiff base and amide adducts, six of which
      have not been reported before. The structures of these new compounds were
      determined by their fragmentation patterns using MS(n) experiments. The new PE
      hexanal adducts contained dimeric and trimeric hexanal conjugates, including
      cyclic adducts. A new pyridine ring containing adduct of DPPE and hexanal was
      purified by HPLC, and its biological effects were investigated. Incubation of
      peripheral blood mononuclear cells and monocytes with modified DPPE did not
      result in increased production of TNF-alpha as one selected inflammation marker.
      However, incorporation of modified DPPE into 1,2-dipalmitoleoyl-sn
      phosphatidylethanolamine multilamellar vesicles resulted in a negative shift of
      the transition temperature, indicating a possible role of alkanal-derived
      modifications in changes of membrane structure.

PMID- 25044842
TI  - Negative charge induced dissociation: fragmentation of deprotonated N-benzylidene
      2-hydroxylanilines in electrospray ionization mass spectrometry.
AB  - Unimolecular reactivities of different N-benzylidene-2-hydroxylaniline anions
      were investigated in gas phase by electrospray ionization tandem mass
      spectrometry. All the collision-induced dissociation spectra of N-benzylidene-2
      hydroxylaniline anions show similar ions at phenyl anions, neutral loss of
      benzonitrile and benzoxazole anions, respectively. The possible fragmentation
      pathway was probed through deuterium labeling and various group substituents
      experiments. Computational results were applied to shed light on the mechanism of
      fragmentation patterns. The proton in the CH=N is reactive in the formation of
      the concerned ions. Its direct transfer to the oxygen results in 2-hydroxyphenyl
      anion. Proton abstraction between benzoxazole and phenyl anion leads to the
      formation of benzene and benzoxazole anion.

PMID- 25044841
TI  - Structural elucidation of new urinary tamoxifen metabolites by liquid
      chromatography quadrupole time-of-flight mass spectrometry.
AB  - In this study, tamoxifen metabolic profiles were investigated carefully.
      Tamoxifen was administered to two healthy male volunteers and one female patient
      suffering from breast cancer. Urinary extracts were analyzed by liquid
      chromatography quadruple time-of-flight mass spectrometry using full scan and
      targeted MS/MS techniques with accurate mass measurement. Chromatographic peaks
      for potential metabolites were selected by using the theoretical [M + H](+) as
      precursor ion in full-scan experiment and m/z 72, 58 or 44 as characteristic
      product ions for N,N-dimethyl, N-desmethyl and N,N-didesmethyl metabolites in
      targeted MS/MS experiment, respectively. Tamoxifen and 37 metabolites were
      detected in extraction study samples. Chemical structures of seven unreported
      metabolites were elucidated particularly on the basis of fragmentation patterns
      observed for these metabolites. Several metabolic pathways containing mono- and
      di-hydroxylation, methoxylation, N-desmethylation, N,N-didesmethylation,
      oxidation and combinations were suggested. All the metabolites were detected in
      the urine samples up to 1 week.

PMID- 25044843
TI  - Comparison of triple quadrupole mass spectrometry and Orbitrap high-resolution
      mass spectrometry in ultrahigh performance liquid chromatography for the
      determination of veterinary drugs in sewage: benefits and drawbacks.
AB  - This paper presents a comparison of triple quadrupole tandem mass spectrometry
      (MS/MS) and Orbitrap high-resolution mass spectrometry (HRMS) combined to
      ultrahigh performance liquid chromatography for the determination of
      glucocorticoids and polyether ionophores in sewage, in order to show the major
      benefits and drawbacks for each mass spectrometry analyser. Overall, HRMS
      measurements have enhanced performance in terms of confirmatory capabilities than
      MS/MS measurements. Moreover, similar limits of quantification, limits of
      detection, linear range and repeatability for glucocorticoids with both the MS/MS
      and HRMS methods were compared, but in the case of polyether ionophores, slightly
      better limits of detection and limits of quantification were obtained with the
      HRMS method because of the high sensitivity obtained when diagnostic ions are
      used for quantification instead of selected reaction monitoring transitions for
      these compounds. The two methods have been applied to the analysis of several
      influent and effluent sewage samples from sewage treatment plants located in the
      Tarragona region (Catalonia, Spain), showing an excellent correlation between the
      two methods.

PMID- 25044844
TI  - Strong ionic interactions in noncovalent complexes between poly(ethylene imine),
      a cationic electrolyte, and Cibacron Blue, a nucleotide mimic--implications for
      oligonucleotide vectors.
AB  - Cationic polymers can bind DNA to form polyplexes, which are noncovalent
      complexes used for gene delivery into the targeted cells. For more insight on
      such biologically relevant systems, the noncovalent complexes between the
      cationic polymer poly(ethylene imine) (PEI) and the nucleotide mimicking dye
      Cibacron Blue F3G-A (CB) were investigated using mass spectrometry methods. Two
      PEIs of low molecular weight were utilized (Mn  ~ 423 and 600 Da). The different
      types of CB anions produced by Na(+)/H(+) exchanges on the three sulfonic acid
      groups of CB and their dehydrated counterparts were responsible for complex
      formation with PEI. The CB anions underwent noncovalent complex formation with
      protonated, but not with sodiated PEI. A higher proportion of cyclic oligomers
      were detected in PEI423 than PEI600, but both architectures formed association
      products with CB. Tandem mass spectrometry studies revealed a significantly
      stronger noncovalent interaction between PEI and dehydrated CB than between PEI
      and intact CB.

PMID- 25044845
TI  - Role of the solvent on the stability of cycloserine under ESI-MS conditions.
AB  - The effects of methanol (M) and acetonitrile (A) on the stability of cycloserine
      (1) have been studied. InfraRed Multiphoton PhotoDissociation (IRMPD)
      spectroscopy of the ionic species from electrospray ionization tandem mass
      spectrometry (ESI-MS) of 1/M and 1/A solutions points to extensive dimerization
      of 1 to cis-3,6-bis(aminooxymethyl)-2,5-piperidinedione (2), while the same
      process is not observed in the ESI-MS of 1/M solutions. 1D and 2D nuclear
      magnetic resonance experiments confirmed these findings by showing that partial
      dimerization of 1 actually takes place at room temperature in acetonitrile even
      before ESI-MS analysis. Comparison of nuclear magnetic resonance and IRMPD
      spectroscopic data from the same 1/A solution suggests that dimerization of
      cycloserine is enhanced in the ESI source.

PMID- 25044846
TI  - DESI analysis of mammalian cell cultures--preparation and method optimisation.
AB  - Desorption electrospray ion source (DESI) is widely used as an MS imaging
      technique. It is a rapid and convenient method of surface analysis, but to date,
      there are methodological obstacles to its application to the analysis of cell
      culture. This study reported optimised conditions for the analysis of cell
      culture samples. Parameters such as the surface, medium removal and sample
      desiccation techniques were assessed as a function of output data quality.
      Supercharging agents, surfactants and optimal parameters for the DESI ion source
      were evaluated for use in cell culture analyses. Data indicated that plastic
      dishes or sodium glass coated with poly-l-lysine and washing cell cultures with
      150 mM ammonium acetate followed by drying with inert gas were superior for DESI
      analyses. The addition of 1 MUM surfactin to the DESI spray solvent significantly
      improved the results for negative and positive ion modes.

PMID- 25044847
TI  - Monitoring time-dependent degradation of phospholipids in sectioned tissues by
      MALDI imaging mass spectrometry.
AB  - Imaging mass spectrometry (IMS) is useful for visualizing the localization of
      phospholipids on biological tissue surfaces creating great opportunities for IMS
      in lipidomic investigations. With advancements in IMS of lipids, there is a
      demand for large-scale tissue studies necessitating stable, efficient and well
      defined sample handling procedures. Our work within this article shows the
      effects of different storage conditions on the phospholipid composition of
      sectioned tissues from mouse organs. We have taken serial sections from mouse
      brain, kidney and liver thaw mounted unto ITO-coated glass slides and stored them
      under various conditions later analyzing them at fixed time points. A global
      decrease in phospholipid signal intensity is shown to occur and to be a function
      of time and temperature. Contrary to the global decrease, oxidized phospholipid
      and lysophospholipid species are found to increase within 2 h and 24 h,
      respectively, when mounted sections are kept at ambient room conditions. Imaging
      experiments reveal that degradation products increase globally across the tissue.
      Degradation is shown to be inhibited by cold temperatures, with sample integrity
      maintained up to a week after storage in -80  degrees C freezer under N2
      atmosphere. Overall, the results demonstrate a timeline of the effects of lipid
      degradation specific to sectioned tissues and provide several lipid species which
      can serve as markers of degradation. Importantly, the timeline demonstrates
      oxidative sample degradation begins appearing within the normal timescale of IMS
      sample preparation of lipids (i.e. 1-2 h) and that long-term degradation is
      global. Taken together, these results strengthen the notion that standardized
      procedures are required for phospholipid IMS of large sample sets, or in studies
      where many serial sections are prepared together but analyzed over time such as
      in 3-D IMS reconstruction experiments.

PMID- 25044848
TI  - New MALDI matrices based on lithium salts for the analysis of hydrocarbons and
      wax esters.
AB  - Lithium salts of organic aromatic acids (lithium benzoate, lithium salicylate,
      lithium vanillate, lithium 2,5-dimethoxybenzoate, lithium 2,5
      dihydroxyterephthalate, lithium alpha-cyano-4-hydroxycinnamate and lithium
      sinapate) were synthesized and tested as potential matrices for the matrix
      assisted laser desorption/ionization (MALDI)-mass spectrometry analysis of
      hydrocarbons and wax esters. The analytes were desorbed using nitrogen laser
      (337.1 nm) and ionized via the attachment of a lithium cation, yielding [M +
      Li](+) adducts. The sample preparation and the experimental conditions were
      optimized for each matrix using stearyl behenate and n-triacontane standards. The
      performance of the new matrices in terms of signal intensity and reproducibility,
      the mass range occupied by matrix ions and the laser power threshold were studied
      and compared with a previously recommended lithium 2,5-dihydroxybenzoate matrix
      (LiDHB) (Cvacka and Svatos, Rapid Commun. Mass Spectrom. 2003, 17, 2203). Several
      of the new matrices performed better than LiDHB. Lithium vanillate offered a 2-3
      times and 7-9 times higher signal for wax esters and hydrocarbons, respectively.
      Also, the signal reproducibility improved substantially, making this matrix a
      suitable candidate for imaging applications. In addition, the diffuse reflectance
      spectra and solubility of the synthesized compounds were investigated and
      discussed with respect to the compound's ability to serve as MALDI matrices. The
      applicability of selected matrices was tested on natural samples of wax esters
      and hydrocarbons.

PMID- 25044849
TI  - Alleviation of ion suppression effect in sonic spray ionization with induced
      alternating current voltage.
AB  - In this study, alleviation of ion suppression effect in sonic spray ionization
      mass spectrometry (SSI-MS) was investigated. Ion suppression effect was firstly
      compared between electrospray ionization (ESI) and conventional SSI, and more
      severe ion suppression effect was observed with SSI. Ion suppression effect of
      SSI was also found difficult to be alleviated by simply optimizing major
      parameters. Alternatively, we found that with the assistance of an alternating
      current (AC) voltage with low amplitude, the ion suppression effect was greatly
      alleviated (comparable with conventional ESI). That AC voltage was applied
      outside the SSI spray tip, and no direct contact between the electrode and spray
      solution was necessary. Besides the alleviation of the ion suppression effect,
      this newly-developed method, termed as induced electrosonic spray ionization
      (IESSI), appeared to preserve similar charge state distribution with SSI for
      protonated cytochrome c, hemoglobin, and bradykinin. IESSI could also obtain
      significantly improved ion intensities (~1000-fold over conventional SSI). In
      addition, tolerance of concentrated salts for IESSI-MS was investigated through
      the analysis of cytochrome c in the presence of concentrated sodium chloride
      (NaCl) or ammonium acetate (NH4 OAc).

PMID- 25044850
TI  - Strategies for differentiation of isobaric flavonoids using liquid chromatography
      coupled to electrospray ionization mass spectrometry.
AB  - Flavonoids are a class of secondary plant metabolites existing in great variety
      in nature. Due to this variety, identification can be difficult, especially as
      overlapping compounds in both chromatographic separations and mass spectrometric
      detection are common. Methods for distinguishing isobaric flavonoids using MS(2)
      and MS(3) have been developed. Chromatographic separation of various plant
      extracts was done with RP-HPLC and detected with positive ESI-MS operated in
      information-dependent acquisition (IDA) mode. Two methods for the determination
      of flavonoid identity and substitution pattern, both featuring IDA criteria, were
      used together with the HPLC equipment. A third method where the collision energy
      was ramped utilized direct infusion. With the developed strategies, it is
      possible to differentiate between many isobaric flavonoids. Various classes of
      flavonoids were found in all of the plant extracts, in the red onion extract 45
      components were detected and for 29 of them the aglycone was characterized, while
      the substituents were tentatively identified for 31 of them. For the strawberry
      extract, those numbers were 66, 30 and 60, and for the cherry extract 99, 56 and
      71. The great variety of flavonoids, several of them isobaric, found in each of
      the extracts highlights the need for reliable methods for flavonoid
      characterization. Methods capable of differentiating between most of the isobars
      analyzed have been developed.

PMID- 25044853
TI  - Relationships between eating quickly and weight gain in Japanese university
      students: a longitudinal study.
AB  - OBJECTIVE: Many cross-sectional studies have reported a relationship between
      overweight/obesity and eating quickly, but there have been few longitudinal
      studies to address this relationship in younger populations. The purpose of this
      prospective longitudinal study was to investigate whether eating quickly was
      related to being overweight in Japanese university students. METHODS: Of 1,396
      students who underwent a general examination and completed questionnaires at the
      start of university and before graduation, 1,314 students (676 male and 638
      female) of normal body composition [body mass index (BMI) < 25 kg m(-2) ] at
      baseline were included in the analysis. The questionnaires included speed of
      eating and other lifestyle factors. After a 3-year follow-up, the students whose
      BMIs were >= 25 kg m(-2) were defined as overweight. RESULTS: In this study, 38
      participants (2.9%) became overweight. In the logistic regression analysis, the
      risk of being overweight was increased in males [adjusted odds ratio (OR): 2.77;
      95% confidence interval (CI): 1.33-5.79; P < 0.01] and in those who ate quickly
      at baseline (OR: 4.40; 95% CI: 2.22-8.75; P < 0.001). CONCLUSIONS: Eating quickly
      may predict risk of being overweight in Japanese university students.

PMID- 25044854
TI  - Hop-derived prenylflavonoids are substrates and inhibitors of the efflux
      transporter breast cancer resistance protein (BCRP/ABCG2).
AB  - SCOPE: Hops (Humulus lupulus L.) produce unique prenylflavonoids that exhibit
      interesting bioactivities. This study investigates the interactions between
      selected prenylflavonoids and breast cancer resistance protein (BCRP/ABCG2), an
      efflux transporter important for xenobiotic bioavailability and multidrug
      resistance (MDR). METHODS AND RESULTS: ABCG2-inhibitory activity of xanthohumol
      (XN), isoxanthohumol (IX), 6-prenylnaringenin (6-PN), 8-prenylnaringenin (8-PN),
      and 6,8-diprenylnarigenin (6,8-diPN) was evaluated using mitoxantrone
      accumulation and vesicular transport assays. XN, IX, and 8-PN were tested for a
      substrate-type relationship with ABCG2 using ATPase and bidirectional transport
      assays. The prenylflavonoids exhibited significant ABCG2-inhibitory activities in
      mitoxantrone accumulation and vesicular transport assays. In the ATPase assay,
      XN, IX, and 8-PN inhibited baseline and sulfasalazine-stimulated ATPase
      activities with IC50 of 2.16-27.0 MUM. IX and 8-PNalso displayed bell-shaped
      activation curves in Ko143-suppressed membranes, indicating a substrate-type
      relationship. For IX, efflux ratios of 1.25 +/- 0.21 and 9.18 +/- 0.56 were
      observed in wild type and ABCG2-overexpressing MDCKII cell monolayers,
      respectively. The latter was reduced to 1.25 +/- 0.15 in the presence of the
      ABCG2-specific inhibitor Ko143, demonstrating an ABCG2-mediated efflux of IX.
      Additionally, evidence was shown for the involvement of ABCG2 in the efflux of 8
      PN and/or its sulfate conjugate. CONCLUSION: Prenylflavonoids are potent
      inhibitors of ABCG2 and therefore implicated in ABCG2-mediated food/herb-drug
      interactions and MDR. ABCG2-mediated efflux of prenylflavonoids may represent one
      mechanism that regulates prenylflavonoid bioavailability.

PMID- 25044855
TI  - Determination of sunitinib in human plasma using liquid chromatography coupled
      with mass spectrometry.
AB  - An original method based on liquid chromatography with single quadrupole
      electrospray ionization mass spectrometry was developed for the determination of
      sunitinib in human plasma. The quantitation limit of the method at 0.10 ng/mL is
      comparable to that of tandem mass spectrometry assays. The handling of all
      solutions containing sunitinib was performed under low-intensity red light to
      avoid the isomerization of sunitinib and enable quantitation using a single peak.
      Liquid-liquid extraction with a mixture of n-hexane/isopropanol (90:10 v/v)
      allowed recoveries at the level of 70%. Measurements were performed using a
      Zorbax SB-C18 column (3.0 mm * 150 mm, 3.5 MUm) and isocratic elution with (A)
      0.1% aqueous formic acid and (B) acetonitrile/methanol (80:20 v/v) in an A/B
      ratio of 55:45 at 35 degrees C. Under these conditions, sunitinib is eluted at
      3.8 min in 6 min of the total run time. The linearity of the calibration curve
      ranges from 0.10 to 150 ng/mL. The baseline separation of sunitinib and its
      primary metabolite, N-des-ethyl sunitinib (SU12662), as well as sharp peak
      shapes, suggest a possibility of extending the applied methodology to the
      quantitative determination of both compounds. Isotopically labeled sunitinib was
      used as the internal standard. All required validation tests met the acceptance
      criteria and proved the method's reliability and robustness. The method may be
      conveniently applied to study the pharmacokinetics of sunitinib in humans.

PMID- 25044856
TI  - Angiopep-conjugated electro-responsive hydrogel nanoparticles: therapeutic
      potential for epilepsy.
AB  - A safe and effective therapy for epilepsy requires a drug delivery system that
      can penetrate the blood-brain barrier and subsequently release antiepileptic
      drugs rapidly to suppress neuronal discharges in a timely manner. We have
      developed electro-responsive hydrogel nanoparticles (ERHNPs) modified with
      angiopep-2 (ANG) to facilitate the delivery of the antiepileptic drug phenytoin
      sodium. The resulting ANG-ERHNPs had an average diameter of (102.3+/-16.8) nm and
      were electro-sensitive with regard to particle size and drug release in vitro.
      ANG-ERHNPs have the characteristics of penetrate the BBB easily, resulting in a
      higher distribution in the central system. The improved antiepileptic effects
      were investigated with the amygdala kindling model. The results demonstrate that
      the ANG-ERHNPs were able to transport antiepileptic drugs into the brain and
      release them under electroencephalograph epileptiform abnormalities to greatly
      improve the therapeutic index of existing drugs in clinical use. 

PMID- 25044857
TI  - GuA6DT, a regiospecific prenyltransferase from Glycyrrhiza uralensis, catalyzes
      the 6-prenylation of flavones.
AB  - GuA6DT, a flavonoid prenyltransferase, was identified from Glycyrrhiza uralensis,
      and it was found that this enzyme regiospecifically transfers a dimethylallyl
      moiety to apigenin at the C-6 position. A further substrate specificity
      investigation indicated that the existence of hydroxyls at both the C-5 and C-7
      positions of the flavone skeleton is critical for the prenylation. However,
      substitutions on the B-ring had negligible influence on the prenylation. A
      comparison of GuA6DT expression in different organs revealed that mRNA is mainly
      expressed in the aerial parts. Moreover, the GuA6DT mRNA was found to be
      regulated at the transcriptional level, because methyl jasmonate induced
      upregulation in cultured cells. GuA6DT is the first identified flavone
      prenyltransferase to exhibit strict substrate specificity and regiospecificity. 

PMID- 25044858
TI  - Protein interactomics based on direct molecular fishing on paramagnetic
      particles: practical realization and further SPR validation.
AB  - There is increasing evidence that proteins function in the cell as integrated
      stable or temporally formed protein complexes, interactomes. Previously, using
      model systems we demonstrated applicability of direct molecular fishing on
      paramagnetic particles for protein interactomics (Ershov et al. Proteomics, 2012,
      12, 3295). In the present study, we have used a combination of affinity-based
      molecular fishing and subsequent MS for investigation of human liver proteins
      involved in interactions with immobilized microsomal cytochrome b5 (CYB5A), and
      also transthyretin and BSA as alternative affinity ligands (baits). The LC-MS/MS
      identification of prey proteins fished on these baits revealed three sets of
      proteins: 98, 120, and 220, respectively. Comparison analysis of these sets
      revealed only three proteins common for all the baits. In the case of paired
      analysis, the number of common proteins varied from 2 to 9. The binding capacity
      of some identified proteins has been validated by a SPR-based biosensor. All the
      investigated proteins effectively interacted with the immobilized CYB5A (Kd
      values ranged from 0.07 to 1.1 MUM). Results of this study suggest that direct
      molecular fishing is applicable for analysis of protein-protein interactions
      (PPI) under normal and pathological conditions, in which altered PPIs are
      especially important.

PMID- 25044860
TI  - A semi-automated method for measuring femoral shape to derive version and its
      comparison with existing methods.
AB  - The measurement of femoral version is important in surgical planning of
      derotational osteotomies particularly for patients with proximal femoral
      deformity. It is, however, difficult to measure version accurately and
      differences of 10 degrees  to 15 degrees  have been found between repeated
      measurements. The aim of this work was first to develop a method of measuring
      femoral version angle where the definition of the neck axis is based on the three
      dimensional point cloud making up the neck, second to automate many of the
      processes involved thus reducing the influence of human error and third to ensure
      the method could run on freely available software suitable for most computer
      platforms. A CT scan was performed on 44 cadaveric femurs to generate point
      clouds of the femoral surfaces. The point clouds were then analysed semi
      automatically to determine femoral version angle between a neck axis defined by
      the bone surface points belonging only to the neck and a femoral condylar axis.
      The results from the neck fitting method were compared against three other
      methods typically used in the clinic (Murphy, Reikeras and Lee methods). Version
      angle measured by the new method gave 19.1 degrees  +/- 7.3 degrees  (mean +/-
      standard deviation) for the set of cadaveric femurs, 3.5 degrees  lower than the
      Murphy method and 6.8 degrees  and 11.0 degrees  higher than the Reikeras and Lee
      2D methods respectively. The results demonstrate a method of measuring femoral
      version angle incorporating a high level of automation running on free software.

PMID- 25044861
TI  - The Psychosocial Work Environment, Employee Mental Health and Organizational
      Interventions: Improving Research and Practice by Taking a Multilevel Approach.
AB  - Although there have been several calls for incorporating multiple levels of
      analysis in employee health and well-being research, studies examining the
      interplay between individual, workgroup, organizational and broader societal
      factors in relation to employee mental health outcomes remain an exception rather
      than the norm. At the same time, organizational intervention research and
      practice also tends to be limited by a single-level focus, omitting potentially
      important influences at multiple levels of analysis. The aims of this conceptual
      paper are to help progress our understanding of work-related determinants of
      employee mental health by the following: (1) providing a rationale for routine
      multilevel assessment of the psychosocial work environment; (2) discussing how a
      multilevel perspective can improve related organizational interventions; and (3)
      highlighting key theoretical and methodological considerations relevant to these
      aims. We present five recommendations for future research, relating to using
      appropriate multilevel research designs, justifying group-level constructs,
      developing group-level measures, expanding investigations to the organizational
      level and developing multilevel approaches to intervention design, implementation
      and evaluation. Copyright (c) 2014 John Wiley & Sons, Ltd. 

PMID- 25044862
TI  - Template-directed FeCo nanoshells on AuCu.
AB  - Schematic AuCu/FeCo core-shell magnetic nanoparticles: FeCo shell is precisely
      synthesized on non-magnetic AuCu core to form the core/shell nanostructures. Due
      to the non-magnetic AuCu core, the FeCo shell exhibits a transition from single
      domain to magnetic vortex state. 

PMID- 25044864
TI  - Considerable methane uptake by alpine grasslands despite the cold climate: in
      situ measurements on the central Tibetan Plateau, 2008-2013.
AB  - The uptake of CH4 by aerate soil plays a secondary role in the removal of
      tropospheric CH4 , but it is still highly uncertain in terms of its magnitude,
      spatial, and temporal variation. In an attempt to quantify the sink of the vast
      alpine grasslands (1,400,000 km(2)) of the Tibetan Plateau, we conducted in situ
      measurements in an alpine steppe (4730 m) and alpine meadow (4900 m) using the
      static chamber and gas chromatograph method. For the alpine steppe, measurements
      (2008-2013) suggested that there is large interannual variability in CH4 uptake,
      ranging from -48.8 to -95.8 MUg CH4 m(-2) h(-1) (averaged of -71.5 +/- 2.5 MUg
      CH4 m(-2) h(-1)), due to the variability in precipitation seasonality. The
      seasonal pattern of CH4 uptakes in the form of stronger uptake in the early
      growing season and weaker uptake in the rainy season closely matched the
      precipitation seasonality and subsequent soil moisture variation. The
      relationships between alpine steppe CH4 uptake and soil moisture/temperature are
      best depicted by a quadratic function and an exponential function (Q10 = 1.67)
      respectively. Our measurements also showed that the alpine meadow soil (average
      of -59.2 +/- 3.7 MUg CH4 m(-2) h(-1)) uptake less CH4 than the alpine steppe and
      produces a similar seasonal pattern, which is negatively regulated by soil
      moisture. Our measurements quantified--at values far higher than those estimated
      by process-based models--that both the alpine steppe and alpine meadow are
      considerable CH4 sinks, despite the cold weather of this high-altitude area. The
      consecutive measurements gathered in this study also highlight that precipitation
      seasonality tends to drive the interannual variation in CH4 uptake, indicating
      that future study should be done to better characterize how CH4 cycling might
      feedback to the more extreme climate.

PMID- 25044863
TI  - Integration of platinum nanoparticles with a volumetric bar-chart chip for
      biomarker assays.
AB  - Platinum nanoparticles (PtNPs) efficiently catalyze the transformation of H2 O2
      into oxygen gas. However, owing to the lack of an efficient approach or device
      that can measure the produced oxygen gas, the catalytic reaction has never been
      used for diagnostic applications. Microfluidics technology provides a platform
      that meets these requirements. The volumetric bar-chart chip (V-Chip)
      volumetrically measures the production of oxygen gas by PtNPs and can be
      integrated with ELISA technology to provide visible and quantitative readouts
      without expensive instrumentation or complicated data processing. Herein we show
      that PtNPs outperform catalase with respect to stability at high H2 O2
      concentrations or temperatures or in long-term reactions, and are resistant to
      most catalase inhibitors. We also show that the catalase-like activity of PtNPs
      can be used in combination with the V-Chip to sensitively and specifically detect
      cancer biomarkers both in serum and on the cell surface. 

PMID- 25044865
TI  - Moving through three-dimensional phase diagrams of monoclonal antibodies.
AB  - Protein phase behavior characterization is a multivariate problem due to the high
      amount of influencing parameters and the diversity of the proteins. Single
      influences on the protein are not understood and fundamental knowledge remains to
      be obtained. For this purpose, a systematic screening method was developed to
      characterize the influence of fluid phase conditions on the phase behavior of
      proteins in three-dimensional phase diagrams. This approach was applied to three
      monoclonal antibodies to investigate influences of pH, protein and salt
      concentrations, with five different salts being tested. Although differences
      exist between the antibodies, this extensive study confirmed the general
      applicability of the Hofmeister series over the broad parameter range analyzed.
      The influence of the different salts on the aggregation (crystallization and
      precipitation) probability was described qualitatively using this Hofmeister
      series, with a differentiation between crystallization and precipitation being
      impossible, however.

PMID- 25044866
TI  - In situ observation of radicals and molecular products during lignin pyrolysis.
AB  - Lignin pyrolysis is a promising method for the sustainable production of phenolic
      compounds from biomass. However, detailed knowledge about the radicals involved
      in this process and their influence on the molecular products is missing. Herein,
      we report on the pyrolysis of hard- and softwood Klason lignins under inert gas
      conditions in a temperature range between 350-550  degrees C. During the
      pyrolysis process, the formed radicals were detected by in situ high-temperature
      electron paramagnetic resonance spectroscopy. The overall formation of volatile
      products during lignin pyrolysis was determined using thermogravimetric analysis.
      The volatile molecular products were characterized and quantified using GC-MS
      analysis. Major differences were observed between hardwood and softwood lignins.
      Hardwood lignins form more radicals and volatile products than softwood lignins
      at temperatures from 350 to 450  degrees C. In the late stages of the pyrolysis
      process at 550  degrees C radical quenching reactions become dominant in hardwood
      lignins. We identified the disproportionation of two semiquinone radicals to
      quinone and hydroquinone species as the most likely quenching reaction. Our
      results show that both the pyrolysis temperature and the type of lignin source
      have a major influence on radical formation and the molecular products during the
      depolymerization of lignin.

PMID- 25044868
TI  - Construction of pendant-armed Schiff-base macrocyclic dinuclear zinc complexes
      and their selective recognition of acetate ions.
AB  - Two new flexible extended dialdehydes (H2hpdd and H2pdd) with different
      functional pendant arms (-CH2CH2PhOH and -CH2CH2Ph) have been synthesized and
      reacted with 1,2-bis(2-aminoethoxy)ethane to prepare Schiff-base macrocyclic
      complexes in the presence of a Zn(II)-ion template. As a result, two preorganized
      dinuclear Zn(II) intermediates (1 and 2), as well as two 42-membered folded [2+2]
      macrocyclic dinuclear Zn(II) complexes (3 and 4), were produced. The central zinc
      ions in compounds 1-4 showed distinguishable coordination patterns with the
      dialdehydes and the [2+2] macrocyclic ligands, in which a subtle pH-adjustment
      function of the two pendant arms (with or without the phenolic hydroxy group) was
      believed to play a vital role. Furthermore, cation- and anion-recognition
      experiments for complexes 3 and 4 revealed that they could selectively recognize
      acetate ions by the formation of 1:1 stoichiometric complexes, as verified by
      changes in their UV/Vis and MS (ESI) spectra and even by the naked eye.

PMID- 25044867
TI  - Cardiovascular event-free survival after adjuvant radiation therapy in breast
      cancer patients stratified by cardiovascular risk.
AB  - The objective of this study was to estimate the risk of a cardiovascular event or
      death associated with modern radiation in a population of elderly female breast
      cancer patients with varying baseline cardiovascular risk. The data used for this
      analysis are from the linked Surveillance, Epidemiology, and End-Results (SEER)
      Medicare database. The retrospective cohort study included women aged 66 years
      and older with stage 0-III breast cancer diagnosed between 2000 and 2005. Women
      were grouped as low, intermediate, or high cardiovascular risk based on the
      presence of certain clinical diagnoses. The risk for the combined outcome of a
      hospitalization for a cardiovascular event or death within 6 months and 24 months
      of diagnosis was estimated using a multivariable Cox model. The median follow-up
      time was 24 months. Among the 91,612 women with American Joint Committee on
      Cancer (AJCC) stage 0-III breast cancer: 39,555 (43.2%) were treated with
      radiation therapy and 52,057 (56.8%) were not. The receipt of radiation therapy
      in the first 6 months was associated with a statistically significant increased
      risk for the combined outcome in women categorized as high risk (HR = 1.510; 95%
      CI, 1.396-1.634) or intermediate risk (HR = 1.415; 95% CI, 1.188-1.686) but not
      low risk (HR = 1.027; 95% CI, 0.798-1.321). Women with a prior medical history of
      cardiovascular disease treated with radiation therapy are at increased risk for
      an event and should be monitored for at least 6 months following treatment with
      radiation therapy. 

PMID- 25044869
TI  - Expedient synthesis of fused azepine derivatives using a sequential rhodium(II)
      catalyzed cyclopropanation/1-aza-Cope rearrangement of dienyltriazoles.
AB  - A general method for the formation of fused dihydroazepine derivatives from 1
      sulfonyl-1,2,3-triazoles bearing a tethered diene is reported. The process
      involves an intramolecular cyclopropanation of an alpha-imino rhodium(II)
      carbenoid, leading to a transient 1-imino-2-vinylcyclopropane intermediate which
      rapidly undergoes a 1-aza-Cope rearrangement to generate fused dihydroazepine
      derivatives in moderate to excellent yields. The reaction proceeds with similar
      efficiency on gram scale. The use of catalyst-free conditions leads to the
      formation of a novel [4.4.0] bicyclic heterocycle. 

PMID- 25044870
TI  - Prediction of myelopathic level in cervical spondylotic myelopathy using
      diffusion tensor imaging.
AB  - PURPOSE: To investigate the use of a newly designed machine learning-based
      classifier in the automatic identification of myelopathic levels in cervical
      spondylotic myelopathy (CSM). MATERIALS AND METHODS: In all, 58 normal volunteers
      and 16 subjects with CSM were recruited for diffusion tensor imaging (DTI)
      acquisition. The eigenvalues were extracted as the selected features from DTI
      images. Three classifiers, naive Bayesian, support vector machine, and support
      tensor machine, and fractional anisotropy (FA) were employed to identify
      myelopathic levels. The results were compared with clinical level diagnosis
      results and accuracy, sensitivity, and specificity were calculated to evaluate
      the performance of the developed classifiers. RESULTS: The accuracy by support
      tensor machine was the highest (93.62%) among the three classifiers. The support
      tensor machine also showed excellent capacity to identify true positives
      (sensitivity: 84.62%) and true negatives (specificity: 97.06%). The accuracy by
      FA value was the lowest (76%) in all the methods. CONCLUSION: The classifiers
      based method using eigenvalues had a better performance in identifying the levels
      of CSM than the diagnosis using FA values. The support tensor machine was the
      best among three classifiers.

PMID- 25044871
TI  - Targetable phosphorescent oxygen nanosensors for the assessment of tumor
      mitochondrial dysfunction by monitoring the respiratory activity.
AB  - Cellular respiration is a worthwhile criterion to evaluate mitochondrial
      dysfunction by measuring the dissolved oxygen. However, most of the existing
      sensing strategies merely report extracellular (ec-) or intracellular (ic-) O2
      rather than intramitochondrial (im-) O2 . Herein we present a method to assess
      tumor mitochondrial dysfunction with three phosphorescent nanosensors, which
      respond to ec-, ic-, and im-O2 . Time-resolved luminescence is applied to
      determine the respective oxygen consumption rates (OCRs) under varying
      respiratory conditions. Data obtained for the OCRs and on (intra)cellular O2
      gradients demonstrate that mitochondria in tumor cells are distinctly less active
      than those of healthy cells, resulting from restrained glucose utilization of and
      physical injury to the mitochondria. We believe that such a site-resolved sensing
      strategy can be applied to numerous other situations, for example to evaluate the
      adverse effects of drug candidates. 

PMID- 25044872
TI  - Retroactive interference of object-in-context long-term memory: role of dorsal
      hippocampus and medial prefrontal cortex.
AB  - Retroactive interference (RI) is a type of amnesia in which a new learning
      experience can impair the expression of a previous one. It has been studied in
      several types of memories for over a century. Here, we aimed to study in the long
      term memory (LTM) formation of an object-in-context task, defined as the
      recognition of a familiar object in a context different to that in which it was
      previously encountered. We trained rats with two sample trials, each taking place
      in a different context in association with different objects. Test sessions were
      performed 24 h later, to evaluate LTM for both object-context pairs using
      separate groups of trained rats. Furthermore, given the involvement of
      hippocampus (Hp) and medial prefrontal cortex (mPFC) in several recognition
      memories, we also analyzed the participation of these structures in the LTM
      formation of this task by the local infusion of muscimol. Our results show that
      object-in-context LTM formation is sensitive to RI by a different either familiar
      or novel object-context pair trial, experienced 1 h later. This interference
      occurs in a restricted temporal window and works on the LTM consolidation phase,
      leaving intact short-term memory expression. The second sample trial did not
      affect the object recognition part of the memory. Besides, muscimol treatment
      before the second sample trial blocks its object-in-context LTM and restores the
      first sample trial memory. We hypothesized that LTM-RI amnesia is probably caused
      by resources or cellular machinery competition in these brain regions when they
      are engaged in memory formation of the traces. In sum, when two different object
      in-context memory traces are being processed, the second trace interferes with
      the consolidation of the first one requiring mPFC and CA1 dorsal Hp activation.

PMID- 25044873
TI  - Toward new fuel cell support materials: a theoretical and experimental study of
      nitrogen-doped graphene.
AB  - Nano-scale Pt particles are often reported to be more electrochemically active
      and stable in a fuel cell if properly displaced on support materials; however,
      the factors that affect their activity and stability are not well understood. We
      applied first-principles calculations and experimental measurements to well
      defined model systems of N-doped graphene supports (N-GNS) to reveal the
      fundamental mechanisms that control the catalytic properties and structural
      integrity of nano-scale Pt particles. DFT calculations predict thermodynamic and
      electrochemical interactions between N-GNS and Pt nanoparticles in the methanol
      oxidation reaction (MOR) and oxygen reduction reaction (ORR). Moreover, the
      dissolution potentials of the Pt nanoparticles supported on GNS and N-GNS
      catalysts are calculated under acidic conditions. Our results provide insight
      into the design of new support materials for enhanced catalytic efficiency and
      long-term stability. 

PMID- 25044874
TI  - Emerging infections, biosecurity and public health.

PMID- 25044875
TI  - Patient-provider discussion of physical activity among early stage lung cancer
      survivors.

PMID- 25044876
TI  - Hypertrophic cardiomyopathy in adults: an overview.
AB  - PURPOSE: To present an overview of clinical issues related to adults with
      hypertrophic cardiomyopathy (HCM), their presenting symptoms, diagnosis, physical
      examination findings, treatment, and follow-up care. DATA SOURCES: A
      comprehensive search of Medline (PubMed) and CINAHL was conducted using the key
      terms HCM, treatment, diagnosis, sudden cardiac death (SCD), and complications.
      This search yielded 21 articles used for this article. There were three reference
      books used for background, diagnosis, and treatment information as well.
      CONCLUSIONS: Although HCM is the most prevalent genetic disorder affecting the
      heart, it often goes undiagnosed until midlife after patients show symptoms of
      myocardial remodeling. Adults with cardiomyopathy suffer SCD or adverse events
      such as stroke and heart failure from HCM. Early diagnosis will prevent SCD,
      improve quality of life, and slow patient's progression to heart failure.
      IMPLICATIONS FOR PRACTICE: Early recognition of HCM in adults by their primary
      care providers will improve patients' quality of life and reduce incidence of
      SCD, heart failure, and stroke.

PMID- 25044877
TI  - Capillary electrophoresis coupled with electrochemiluminescence for determination
      of atomoxetine hydrochloride and the study on its interactions with three
      proteins.
AB  - A simple, rapid and sensitive method for the determination of atomoxetine
      hydrochloride (AH) by capillary electrophoresis with electrochemiluminescence
      detection (CE-ECL) using tris(2,2'-bipyridyl) ruthenium (II) was developed. Under
      optimized conditions, the determinations of AH in capsules and rat plasmas and
      the study on its interactions with three plasma proteins, including bovine serum
      albumin, cytochrome c and myoglobin were performed successfully. Relative to some
      previous studies, in this paper the methodologies for the determination of AH in
      aqueous solution and spiked plasma systems were established, respectively. By
      comparing the difference between the two work curves of two systems, the matrix
      effect in plasma samples on the determination of AH by the CE-ECL method was
      discussed in detail. The results indicated that the effect of the matrix in
      plasma samples should not be ignored even if no obvious interference was found in
      the electropherograms and the establishment of method validation in complex
      samples by the CE-ECL method was necessary.

PMID- 25044878
TI  - The cumulative impact of annual coral bleaching can turn some coral species
      winners into losers.
AB  - Mass coral bleaching events caused by elevated seawater temperatures result in
      extensive coral loss throughout the tropics, and are projected to increase in
      frequency and severity. If bleaching becomes an annual event later in this
      century, more than 90% of coral reefs worldwide may be at risk of long-term
      degradation. While corals can recover from single isolated bleaching and can
      acclimate to recurring bleaching events that are separated by multiple years, it
      is currently unknown if and how they will survive and possibly acclimatize to
      annual coral bleaching. Here, we demonstrate for the first time that annual coral
      bleaching can dramatically alter thermal tolerance in Caribbean corals. We found
      that high coral energy reserves and changes in the dominant algal endosymbiont
      type (Symbiodinium spp.) facilitated rapid acclimation in Porites divaricata,
      whereas low energy reserves and a lack of algal phenotypic plasticity
      significantly increased susceptibility in Porites astreoides to bleaching the
      following year. Phenotypic plasticity in the dominant endosymbiont type of
      Orbicella faveolata did not prevent repeat bleaching, but may have facilitated
      rapid recovery. Thus, coral holobiont response to an isolated single bleaching
      event is not an accurate predictor of its response to bleaching the following
      year. Rather, the cumulative impact of annual coral bleaching can turn some coral
      species 'winners' into 'losers', and can also facilitate acclimation and turn
      some coral species 'losers' into 'winners'. Overall, these findings indicate that
      cumulative impact of annual coral bleaching could result in some species becoming
      increasingly susceptible to bleaching and face a long-term decline, while
      phenotypically plastic coral species will acclimatize and persist. Thus, annual
      coral bleaching and recovery could contribute to the selective loss of coral
      diversity as well as the overall decline of coral reefs in the Caribbean. 

PMID- 25044879
TI  - Functionalized graphene as a gatekeeper for chiral molecules: an alternative
      concept for chiral separation.
AB  - We propose a new method of chiral separation using functionalized nanoporous
      graphene as an example. Computational simulations based on density functional
      theory show that the attachment of a suitable chiral "bouncer" molecule to the
      pore rim prevents the passage of the undesired enantiomer while letting its
      mirror image through. 

PMID- 25044880
TI  - Wilms tumor 1/cytokeratin dual-color immunostaining reveals distinctive staining
      patterns in metastatic melanoma, metastatic carcinoma, and mesothelial cells in
      pleural fluids: an effective first-line test for the workup of malignant
      effusions.
AB  - BACKGROUND: The workup of a malignant effusion usually requires immunostaining
      with a panel of markers. Although nuclear Wilms tumor 1 (WT1) expression is
      widely used to detect tumors of ovarian and mesothelial origin, it is less well
      known that WT1 is also expressed in the cytoplasm of melanomas and mesenchymal
      tumors. Because to the authors' knowledge the diagnostic utility of cytoplasmic
      WT1 expression has not been explored to date, the usefulness of a WT1/AE1/AE3
      dual-color immunostain in the workup of malignant effusions was evaluated.
      METHODS: A total of 86 pleural effusions, including 17 metastatic melanomas, 31
      metastatic adenocarcinomas, 10 malignant mesotheliomas, 10 lymphoproliferative
      disorders, 5 metastatic sarcomas, and 13 benign specimens, were immunostained
      using a peroxidase-based brown chromogen for WT1 and an alkaline phosphatase
      based red chromogen for AE1/AE3 on cell block sections. RESULTS: The majority of
      malignant effusions stained in 1 of 4 distinctive patterns: 1) all lung and
      breast adenocarcinomas demonstrated cytoplasmic AE1/AE3 expression without
      nuclear or cytoplasmic WT1 expression; 2) serous carcinomas of Mullerian origin,
      mesotheliomas, and benign mesothelial cells were positive for cytoplasmic AE1/AE3
      as well as nuclear WT1; 3) melanomas, sarcomas, and a subset of plasma cell
      neoplasms were positive for cytoplasmic expression of WT1 but negative for
      AE1/AE3; and 4) large B-cell lymphomas and a subset of plasma cell neoplasms were
      negative for both markers. CONCLUSIONS: A WT1/AE1/AE3 dual-color immunostain can
      reliably identify malignancy in pleural effusions and group malignant cells into
      discrete subsets, thereby narrowing the differential diagnosis. This simple
      double stain can be a cost-effective, first-line test in the workup of patients
      with malignant effusions.

PMID- 25044881
TI  - The double inhibition of endogenously produced BMP and Wnt factors
      synergistically triggers dorsal telencephalic differentiation of mouse ES cells.
AB  - Embryonic stem (ES) cells are becoming a popular model of in vitro neurogenesis,
      as they display intrinsic capability to generate neural progenitors that undergo
      the known steps of in vivo neural development. These include the acquisition of
      distinct regional fates, which depend on growth factors and signals that are
      present in the culture medium. The control of the intracellular signaling that is
      active at different steps of ES cell neuralization, even when cells are cultured
      in chemically defined medium, is complicated by the endogenous production of
      growth factors. However, this endogenous production has been poorly investigated
      so far. To address this point, we performed a high-throughput analysis of the
      expression of morphogens during mouse ES cell neuralization in minimal medium. We
      found that during their neuralization, ES cells increased the expression of
      members of Wnt, Fibroblast Growth Factor (FGF), and BMP families. Conversely, the
      expression of Activin/Nodal and Shh ligands was low in early steps of
      neuralization. In this experimental condition, neural progenitors and neurons
      generated by ES cells expressed a gene expression profile that was consistent
      with a midbrain identity. We found that endogenous BMP and Wnt signaling, but not
      FGF signaling, synergistically affected ES cell neural patterning, by turning off
      a profile of dorsal/telencephalic gene expression. Double BMP and Wnt inhibition
      allowed neuralized ES cells to sequentially activate key genes of cortical
      differentiation. Our findings are consistent with a novel synergistic effect of
      Wnt and BMP endogenous signaling of ES cells in inhibiting a cortical
      differentiation program.

PMID- 25044882
TI  - Gain-of-Function Mutation in STIM1 (P.R304W) Is Associated with Stormorken
      Syndrome.
AB  - Stormorken syndrome is a rare autosomal dominant disorder characterized by a
      phenotype that includes miosis, thrombocytopenia/thrombocytopathy with bleeding
      time diathesis, intellectual disability, mild hypocalcemia, muscle fatigue,
      asplenia, and ichthyosis. Using targeted sequencing and whole-exome sequencing,
      we identified the c.910C > T transition in a STIM1 allele (p.R304W) only in
      patients and not in their unaffected family members. STIM1 encodes stromal
      interaction molecule 1 protein (STIM1), which is a finely tuned endoplasmic
      reticulum Ca(2+) sensor. The effect of the mutation on the structure of STIM1 was
      investigated by molecular modeling, and its effect on function was explored by
      calcium imaging experiments. Results obtained from calcium imaging experiments
      using transfected cells together with fibroblasts from one patient are in
      agreement with impairment of calcium homeostasis. We show that the STIM1 p.R304W
      variant may affect the conformation of the inhibitory helix and unlock the
      inhibitory state of STIM1. The p.R304W mutation causes a gain of function effect
      associated with an increase in both resting Ca(2+) levels and store-operated
      calcium entry. Our study provides evidence that Stormorken syndrome may result
      from a single-gene defect, which is consistent with Mendelian-dominant
      inheritance. 

PMID- 25044883
TI  - Smoc2 modulates embryonic myelopoiesis during zebrafish development.
AB  - BACKGROUND: SMOC2 is a member of the BM-40 (SPARC) family of matricellular
      proteins, reported to influence signaling in the extracellular compartment. In
      mice, Smoc2 is expressed in many different tissues and was shown to enhance the
      response to angiogenic growth factors, mediate cell adhesion, keratinocyte
      migration, and metastasis. Additionally, SMOC2 is associated with vitiligo and
      craniofacial and dental defects. The function of Smoc2 during early zebrafish
      development has not been determined to date. RESULTS: In pregastrula zebrafish
      embryos, smoc2 is expressed ubiquitously. As development progresses, the
      expression pattern becomes more anteriorly restricted. At the onset of blood cell
      circulation, smoc2 morphants presented a mild ventralization of posterior
      structures. Molecular analysis of the smoc2 morphants indicated myelopoietic
      defects in the rostral blood islands during segmentation stages. Hemangioblast
      development and further specification of the myeloid progenitor cells were shown
      to be impaired. Additional experiments indicated that Bmp target genes were down
      regulated in smoc2 morphants. CONCLUSIONS: Our findings reveal that Smoc2 is an
      essential player in the development of myeloid cells of the anterior lateral
      plate mesoderm during embryonic zebrafish development. Furthermore, our data show
      that Smoc2 affects the transcription of Bmp target genes without affecting
      initial dorsoventral patterning or mesoderm development.

PMID- 25044885
TI  - Potential of bone marrow mesenchymal stem cells in management of Alzheimer's
      disease in female rats.
AB  - Alzheimer's disease (AD) has been called the disease of the century with
      significant clinical and socioeconomic impacts. Pharmacological treatment has
      limited efficacy and only provides symptomatic relief without long-term cure.
      Accordingly, there is an urgent need to develop novel and effective medications
      for AD. Stem cell-based therapy is a promising approach to handling
      neurodegenerative diseases. Therefore, the current study aimed to explore the
      possible therapeutic role of single intravenous injection of bone marrow derived
      mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the
      experimental model. The work also extended to compare the therapeutic potential
      of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin
      administered daily. BM-MSCs were able to home at the injured brains and produced
      significant increases in the number of positive cells for choline
      acetyltransferase (ChAT) and survivin expression, as well as selective AD
      indicator-1 (seladin-1) and nestin gene expression. Histopathological examination
      indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus.
      Significant improvement in these biomarkers was similar to or better sometimes
      than the reference drugs, clearly showing the potential therapeutic role of BM
      MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory
      properties.

PMID- 25044886
TI  - Chemical modification of a synthetic small molecule boosts its biological
      efficacy against pluripotency genes in mouse fibroblasts.
AB  - A synthetic transcriptional activator encompassing both sequence-specific pyrrole
      imidazole polyamides (PIPs) and an epigenetic activator (suberoylanilide
      hydroxamic acid) was recently shown to induce the endogenous expression of core
      pluripotency genes in mouse embryonic fibroblasts (MEFs). Microarray data
      analysis suggested Oct-3/4 as the probable target pathway of the activator.
      However, the expression levels in MEFs treated with the activator were relatively
      lower than those in mouse embryonic stem cells. Herein, we report studies carried
      out to improve the efficacy of the activator and show that the biological
      activity was significantly (p<0.05) improved against the core pluripotency genes
      after the incorporation of an isophthalic acid (IPA) at the C terminus. The
      resultant IPA conjugate dramatically induced Oct-3/4 and demonstrated a new
      chemical strategy for developing PIP conjugates as next-generation genetic
      switches. 

PMID- 25044884
TI  - Evoked effective connectivity of the human neocortex.
AB  - The role of cortical connectivity in brain function and pathology is increasingly
      being recognized. While in vivo magnetic resonance imaging studies have provided
      important insights into anatomical and functional connectivity, these
      methodologies are limited in their ability to detect electrophysiological
      activity and the causal relationships that underlie effective connectivity. Here,
      we describe results of cortico-cortical evoked potential (CCEP) mapping using
      single pulse electrical stimulation in 25 patients undergoing seizure monitoring
      with subdural electrode arrays. Mapping was performed by stimulating adjacent
      electrode pairs and recording CCEPs from the remainder of the electrode array.
      CCEPs reliably revealed functional networks and showed an inverse relationship to
      distance between sites. Coregistration to Brodmann areas (BA) permitted group
      analysis. Connections were frequently directional with 43% of early responses and
      50% of late responses of connections reflecting relative dominance of incoming or
      outgoing connections. The most consistent connections were seen as outgoing from
      motor cortex, BA6-BA9, somatosensory (SS) cortex, anterior cingulate cortex, and
      Broca's area. Network topology revealed motor, SS, and premotor cortices along
      with BA9 and BA10 and language areas to serve as hubs for cortical connections.
      BA20 and BA39 demonstrated the most consistent dominance of outdegree
      connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated
      relatively greater indegree. This multicenter, large-scale, directional study of
      local and long-range cortical connectivity using direct recordings from awake,
      humans will aid the interpretation of noninvasive functional connectome studies.

PMID- 25044887
TI  - Escherichia coli adhesion, biofilm development and antibiotic susceptibility on
      biomedical materials.
AB  - The aim of this work was to test materials typically used in the construction of
      medical devices regarding their influence in the initial adhesion, biofilm
      development and antibiotic susceptibility of Escherichia coli biofilms. Adhesion
      and biofilm development was monitored in 12-well microtiter plates containing
      coupons of different biomedical materials--silicone (SIL), stainless steel (SS)
      and polyvinyl chloride (PVC)--and glass (GLA) as control. The susceptibility of
      biofilms to ciprofloxacin and ampicillin was assessed, and the antibiotic effect
      in cell morphology was observed by scanning electron microscopy. The surface
      hydrophobicity of the bacterial strain and materials was also evaluated from
      contact angle measurements. Surface hydrophobicity was related with initial E.
      coli adhesion and subsequent biofilm development. Hydrophobic materials, such as
      SIL, SS, and PVC, showed higher bacterial colonization than the hydrophilic GLA.
      Silicone was the surface with the greatest number of adhered cells and the
      biofilms formed on this material were also less susceptible to both antibiotics.
      It was found that different antibiotics induced different levels of elongation on
      E. coli sessile cells. Results revealed that, by affecting the initial adhesion,
      the surface properties of a given material can modulate biofilm buildup and
      interfere with the outcome of antimicrobial therapy. These findings raise the
      possibility of fine-tuning surface properties as a strategy to reach higher
      therapeutic efficacy.

PMID- 25044888
TI  - High content imaging for the morphometric diagnosis and immunophenotypic
      prognosis of canine lymphomas.
AB  - BACKGROUND: The common, symptomatic form of canine lymphoma (multicentric, medium
      to-large cell, advanced) is consistently diagnosed manually and qualitatively by
      veterinary cytologists mainly based on increased lymphocyte size. The most
      effective prognostic feature is immunophenotype based on dual-antibody labeling
      for T versus B cells. High content imaging (HCI) is a novel, semi-automated,
      fluorescence microscopy and image-analysis technology used in research and
      predictive toxicology. OBJECTIVE: We tested the hypothesis that HCI could semi
      automatize the quantitative diagnosis of canine lymphoma and simultaneously
      determine immunophenotypic prognosis. METHODS: Lymphocytes were obtained from
      lymph nodes of six lymphoma-free and five lymphomatous dogs, stained with
      antibodies against CD21 and CD3 (B- vs. T-cells), Hoechst-33342 and seeded into
      96-well plates. Morphological parameters were examined: (a) cell area, (b)
      nuclear area, (c) nuclear displacement, (d) cytoplasmic area, (e) nucleus to cell
      area ratio (N/Cell), (f) nucleus to cytoplasm ratio (N/Cyt), and (g) cell
      roundness. RESULTS: HCI unequivocally discriminated malignant from benign
      lymphocytes, and provided immunophenotype. Cell and cytoplasmic area, nuclear
      displacement and roundness showed biggest differences and the means for each of
      the samples were not overlapping between the two groups. Mean/median/SD for
      control versus lymphoma samples were: (a) cell area (um(2) ): 55.5/53.6/7.5
      versus 80.3/75.5/8.7, (b) nuclear area (um(2) ): 33.4/34.8/3.5 versus
      40.2/38.5/5, (c) cytoplasm area (um(2) ): 22.1/21/6.2 versus 40/38.4/4.9, (d)
      N/cell: 0.62/0.62/0.06 versus 0.52/0.52/0.03, (e) nuclear displacement (arbitrary
      units): 0.139/0.149/0.055 versus 0.33/0.30/0.056, (f) N/Cyt: 1.84/1.76/0.44
      versus 1.19/1.24/0.17, and (g) roundness index: 1.22/1.21/0.03 versus 1.42/
      1.42/0.11 (P < 0.05 for all). CONCLUSION: HCI identified several, novel,
      morphometric parameters that effectively diagnose the common, symptomatic form of
      canine lymphoma, and also simultaneously determine prognostic immunophenotype.

PMID- 25044889
TI  - Time-resolved, in situ DRIFTS/EDE/MS studies on alumina-supported rhodium
      catalysts: effects of ceriation and zirconiation on rhodium-CO interactions.
AB  - The effects of ceria and zirconia on the structure-function properties of
      supported rhodium catalysts (1.6 and 4 wt % Rh/gamma-Al2O3) during CO exposure
      are described. Ceria and zirconia are introduced through two preparation methods:
      1) ceria is deposited on gamma-Al2O3 from [Ce(acac)3] and rhodium metal is
      subsequently added, and 2) through the controlled surface modification (CSM)
      technique, which involves the decomposition of [M(acac)x] (M=Ce, x=3; M=Zr, x=4)
      on Rh/gamma-Al2O3. The structure-function correlations of ceria and/or zirconia
      doped rhodium catalysts are investigated by diffuse reflectance infrared Fourier
      transform spectroscopy/energy-dispersive extended X-ray absorption
      spectroscopy/mass spectrometry (DRIFTS/EDE/MS) under time-resolved, in situ
      conditions. CeOx and ZrO2 facilitate the protection of Rh particles against
      extensive oxidation in air and CO. Larger Rh core particles of ceriated and
      zirconiated Rh catalysts prepared by CSM are observed and compared with Rh/gamma
      Al2O3 samples, whereas supported Rh particles are easily disrupted by CO forming
      mononuclear Rh geminal dicarbonyl species. DRIFTS results indicate that, through
      the interaction of CO with ceriated Rh particles, a significantly larger amount
      of linear CO species form; this suggests the predominance of a metallic Rh phase.

PMID- 25044890
TI  - Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and
      acrodysostosis type 2.
AB  - Acroscyphodysplasia (OMIM250215) is a distinctive form of metaphyseal dysplasia
      characterized by the distal femoral and proximal tibial epiphyses embedded in cup
      shaped, large metaphyses known as metaphyseal scypho ("scypho" = cup) deformity.
      It is also associated with severe growth retardation and brachydactyly. The
      underlying molecular mechanism of acroscyphodysplasia has not yet been
      elucidated, although scypho-deformity of the knee has been reported in three
      patients with acrodysostosis due to a mutation in the PDE4D gene. We report on
      the clinical, radiological, and molecular findings of five female patients with
      acroscyphodysplasia; two were diagnosed as pseudohypoparathyroidism (PHP) or
      Albright hereditary osteodystropy, and the other three as acrodysostosis. They
      all had radiological findings consistent with severe metaphyseal scypho-deformity
      and brachydactyly. Heterozygous mutations were identified in the PHP patients
      consisting of one novel (p.Q19X) and one recurrent (p.R231C) mutation of the GNAS
      gene, as well as, in the acrodysostosis patients consisting of two novel
      mutations (p.T224I and p.I333T) of the PDE4D gene. We conclude that metaphyseal
      acroscyphodysplasia is a phenotypic variation of PHP or acrodysostosis caused by
      either a GNAS or PDE4D mutation, respectively.

PMID- 25044891
TI  - Rapid access to beta-trifluoromethyl-substituted ketones: harnessing inductive
      effects in Wacker-type oxidations of internal alkenes.
AB  - We present a practical trifluoromethyl-directed Wacker-type oxidation of internal
      alkenes that enables rapid access to beta-trifluoromethyl-substituted ketones.
      Allylic trifluoromethyl-substituted alkenes bearing a wide range of functional
      groups can be oxidized in high yield and regioselectivity. The distance
      dependence of the regioselectivity was established by systematic variation of the
      number of methylene units between the double bond and the trifluoromethyl group.
      The regioselectivity enforced by traditional directing groups could even be
      reversed by introduction of a competing trifluoromethyl group. Besides being a
      new powerful synthetic method to prepare fluorinated molecules, this work
      directly probes the role of inductive effects on nucleopalladation events. 

PMID- 25044892
TI  - Mechanism of back electron transfer in an intermolecular photoinduced electron
      transfer reaction: solvent as a charge mediator.
AB  - Back electron transfer (BET) is one of the important processes that govern the
      decay of generated ion pairs in intermolecular photoinduced electron transfer
      reactions. Unfortunately, a detailed mechanism of BET reactions remains largely
      unknown in spite of their importance for the development of molecular
      photovoltaic structures. Here, we examine the BET reaction of pyrene (Py) and 1,4
      dicyanobenzene (DCB) in acetonitrile (ACN) by using time-resolved near- and mid
      IR spectroscopy. The Py dimer radical cation (Py2(.+)) and DCB radical anion
      (DCB(.-)) generated after photoexcitation of Py show asynchronous decay kinetics.
      To account for this observation, we propose a reaction mechanism that involves
      electron transfer from DCB(.-) to the solvent and charge recombination between
      the resulting ACN dimer anion and Py2(.+). The unique role of ACN as a charge
      mediator revealed herein could have implications for strategies that retard
      charge recombination in dye-sensitized solar cells.

PMID- 25044893
TI  - A derivatization and validation strategy for determining the spatial localization
      of endogenous amine metabolites in tissues using MALDI imaging mass spectrometry.
AB  - Imaging mass spectrometry (IMS) studies increasingly focus on endogenous small
      molecular weight metabolites and consequently bring special analytical
      challenges. Since analytical tissue blanks do not exist for endogenous
      metabolites, careful consideration must be given to confirm molecular identity.
      Here, we present approaches for the improvement in detection of endogenous amine
      metabolites such as amino acids and neurotransmitters in tissues through chemical
      derivatization and matrix-assisted laser desorption/ionization (MALDI) IMS.
      Chemical derivatization with 4-hydroxy-3-methoxycinnamaldehyde (CA) was used to
      improve sensitivity and specificity. CA was applied to the tissue via MALDI
      sample targets precoated with a mixture of derivatization reagent and ferulic
      acid as a MALDI matrix. Spatial distributions of chemically derivatized
      endogenous metabolites in tissue were determined by high-mass resolution and
      MS(n) IMS. We highlight an analytical strategy for metabolite validation whereby
      tissue extracts are analyzed by high-performance liquid chromatography (HPLC)
      MS/MS to unambiguously identify metabolites and distinguish them from isobaric
      compounds.

PMID- 25044894
TI  - Determination of human muscle protein fractional synthesis rate: an evaluation of
      different mass spectrometry techniques and considerations for tracer choice.
AB  - In the present study, different MS methods for the determination of human muscle
      protein fractional synthesis rate (FSR) using [ring-(13)C6 ]phenylalanine as a
      tracer were evaluated. Because the turnover rate of human skeletal muscle is
      slow, only minute quantities of the stable isotopically labeled amino acid will
      be incorporated within the few hours of a typical laboratory experiment. GC
      combustion isotope ratio MS (GC-C-IRMS) has thus far been considered the 'gold'
      standard for the precise measurements of these low enrichment levels. However,
      advances in liquid chromatography-tandem MS (LC-MS/MS) and GC-tandem MS (GC
      MS/MS) have made these techniques an option for human muscle FSR measurements.
      Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino
      acids derivatized using either N-acetyl-n-propyl, phenylisothiocyanate, or N
      methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) for GC-C-IRMS, LC
      MS/MS, and GC-MS/MS analysis, respectively. A second derivative,
      heptafluorobutyric acid (HFBA), was also used for GC-MS/MS analysis as an
      alternative for MTBSTFA. The machine reproducibility or the coefficients of
      variation for delta tracer-tracee-ratio measurements (delta tracer-tracee-ratio
      values around 0.0002) were 2.6%, 4.1%, and 10.9% for GC-C-IRMS, LC-MS/MS, and GC
      MS/MS (MTBSTFA), respectively. FSR determined with LC-MS/MS compared well with GC
      C-IRMS and so did the GC-MS/MS when using the HFBA derivative (linear fit Y =
      1.08 +/- 0.10, X + 0.0049 +/- 0.0061, r = 0.89 +/- 0.01, P < 0.0001). In
      conclusion, (1) IRMS still offers the most precise measurement of human muscle
      FSR, (2) LC-MS/MS comes quite close and is a good alternative when tissue
      quantities are too small for GC-C-IRMS, and (3) If GC-MS/MS is to be used, then
      the HFBA derivative should be used instead of MTBSTFA, which gave unacceptably
      high variability.

PMID- 25044895
TI  - Determination of the enrichment of isotopically labelled molecules by mass
      spectrometry.
AB  - A general method for the determination of the enrichment of isotopically labelled
      molecules by mass spectrometry (MS) is described. In contrast to other published
      procedures, the method described here takes into account and corrects for
      measurement errors such as the contribution at M - 1 due to loss of hydrogen or
      lack of spectral resolution and provides an uncertainty value for the determined
      enrichment. The general procedure requires the following steps: (1) evaluation of
      linearity in the mass spectrometer by injecting the natural abundance compound at
      different concentration levels, (2) determination of the purity of the mass
      cluster using the natural abundance analogue, (3) calculation of the theoretical
      isotope composition of the labelled compound using different tentative isotope
      enrichments, (4) calculation of 'convoluted' isotope distributions for the
      labelled compound taking into account the purity of the mass cluster determined
      with the natural abundance analogue and (5) comparison of the isotope
      distributions measured for the labelled compound with those calculated for
      different isotope enrichments using linear regression. The method was applied to
      a series of commercially available (13)C- and (2)H-labelled compounds and to a
      suite of singly (13)C-labelled beta2-agonist prepared in-house both by gas
      chromatography (GC)-MS, GC-tandem MS (MS/MS) and liquid chromatography-MS/MS with
      satisfactory results. It was observed that the main uncertainty source for the
      isotope enrichment was the uncertainty in the purity of the measured cluster as
      determined with the natural abundance compound.

PMID- 25044896
TI  - Selectivity of gas-phase ion/molecule reaction of carbon dioxide with phenide
      ions.
AB  - On contrary to the widely accepted conviction that the m/z 93 ion derived from
      phenol does not react with CO2, we demonstrate that it makes an adduct with CO2
      to a small but demonstrable extent. For example, the product-ion mass spectrum
      recorded for the m/z 98 ion derived from [(2)H6]phenol showed a small peak at m/z
      142 when CO2 was used as the collision gas. The formation of an m/z 137 adduct
      ion from the m/z 93 ion (generated either directly from phenol, or indirectly
      from salicylic acid by in-source decarboxylation) was demonstrated also by
      multiple-reaction-monitoring tandem mass spectrometric experiments. According to
      literature, the m/z 93 ion derived from salicylic acid does not undergo CO2
      addition because it is deemed to exist only in the phenoxide form. This reaction
      has been previously proposed as a method for differentiating phenoxide ion from
      its isomeric hydroxyphenide ions. We propose that the m/z 93 ion, albeit small,
      exists also as the phenide form together with the predominant phenoxide ion.

PMID- 25044897
TI  - Tautomerism and proton transfer in photoionized acetaldehyde and acetaldehyde
      water clusters.
AB  - Understanding the gas-phase chemistry of acetaldehyde can be challenging because
      the molecule can assume several tautomeric forms, namely keto, enol and carbene.
      The two last forms are the most stable ionic forms. Here, insight into the gas
      phase cluster ion chemistry of homogeneous acetaldehyde and mixed water
      acetaldehyde clusters is provided by mass spectrometry/vacuum ultraviolet
      photoionization combined with density functional theory calculations. (AA)nH(+)
      clusters (AA = acetaldehyde) and mixed (AA)nH3O(+) clusters were detected using
      tunable vacuum ultraviolet photoionization. Barrierless proton transfers were
      observed during the geometry optimization of the most stable dimer structures and
      helped to explain the cluster ion chemistry induced by photoionization, namely
      the formation of deprotonated tautomers and protonated keto tautomers. Water was
      found to catalyze the keto-enol and keto-carbene isomerizations and facilitate
      the proton transfer from the ionized enol or carbene part of the cluster to the
      neutral keto part, resulting in protonated keto structures. The production of
      protonated keto structures was identified to be the main fragmentation channel
      following ionization of the homogeneous acetaldehyde cluster and a channel for
      ionized mixed clusters as well. These findings are significant for a broad range
      of fields, including current atmospheric models, because acetaldehyde is one of
      the most prominent organic species in the troposphere and ions play a crucial
      role in aerosol formation.

PMID- 25044898
TI  - Rapid analysis of lubricants by atmospheric solid analysis probe-ion mobility
      mass spectrometry.
AB  - Formulated lubricants are complex mixtures composed of base oil(s) and additives
      with various functions (detergents, corrosion inhibiter, antioxidant, viscosity
      modifiers, etc.). Because of the aliphatic nature of base oil and the chemical
      diversity of additives, the characterization of lubricant is currently a long and
      complex process. The comprehensive analysis of lubricant samples involves several
      techniques such as nuclear magnetic resonance, mass spectrometry, chromatography
      and infrared spectroscopy. The coupling of atmospheric solid analysis probe
      (ASAP) with ion mobility-mass spectrometry (IM-MS) has been shown to be an
      efficient tool for the characterization of complex mixture containing vaporizable
      polar to non-polar compounds. This approach affords the coupling of a direct
      ionization technique that does not require sample preparation, with a bi
      dimensional separation method with high peak capacity. In this work, we show that
      ASAP-IM-MS is a suitable method for rapid and direct characterization of
      lubricant samples. Indeed, base oil and additives yielded, by ASAP, ions series
      which could be separated by IM-MS. Molecular additives such as Zn
      dithiocarbamate, phosphite, thiophosphate and Alkyl diphenylamine were ionized as
      molecular ions [M](+*) or protonated molecules [M + H](+), depending of their
      polarity. In some cases, fragment ions were observed, confirming the additive
      identification. In addition, high molecular weight polymeric additives such as
      poly(alkyl methacrylate) (PAM) were pyrolized in the ASAP source leading to
      characteristic fragment ions. ASAP-IM-MS is shown to be a powerful tool for
      studying complex mixtures, allowing the first comprehensive analysis of
      lubricants in just a few minutes.

PMID- 25044899
TI  - Study of solid/gas phase photocatalytic reactions by electron ionization mass
      spectrometry.
AB  - This paper describes a novel methodology for the real-time study of solid-gas
      phase photocatalytic reactions in situ. A novel reaction chamber has been
      designed and developed to facilitate the investigation of photoactive materials
      under different gas compositions. UV irradiation in the wavelength of ranges 376
      387 and 381-392 nm was provided using specially designed high efficiency light
      emitting diode arrays. The experiments used air containing 190 ppm NO2 in a moist
      environment with a relative humidity of 0.1%. Photocatalytic samples consisting
      of pressed pellets of rutile and anatase crystalline forms of TiO2 were monitored
      over a period of 150 min. An ultra-high vacuum right angled bleed valve allowed a
      controlled flow of gas from the main reaction chamber at atmospheric pressure to
      a residual gas analyser operating at a vacuum of 10(-5)  mbar. The apparatus and
      methodology have been demonstrated to provide high sensitivity (ppb). The rate of
      degradation of NO2 attributed to reaction at the TiO2 surface was sensitive to
      both crystal structures (anatase or rutile) and wavelength of irradiation.

PMID- 25044900
TI  - Evaluation of the optimization space for atmospheric pressure photoionization
      (APPI) in comparison with APCI.
AB  - The usefulness of atmospheric pressure photoionization (APPI) is difficult to
      evaluate for unknowns due to the fragmented literature. Specifically, the
      variation of dopants with a wide set of compounds or the use of APPI in the
      negative mode have rarely been explored. Thirty compounds were selected that were
      not suitable for ESI with a wide variety of functional groups and investigated
      with atmospheric pressure chemical ionization (APCI) and APPI in the positive and
      negative ion modes. The influence of the mobile phase (eluents containing
      acetonitrile or methanol) and--for APPI--four different dopants (acetone,
      chlorobenzene, toluene, and toluene/anisole) were explored. Stepwise variation of
      the organic mobile phase allowed to elucidate the ionization mechanism.
      Atmospheric pressure photoionization was especially useful for compounds, where
      the M(?+) and not the [M + H](+) was formed. The dopants chlorobenzene and
      anisole promoted the formation of molecular ions M(?+) for about half of the
      compounds, and its formation was also positively influenced by the use of mobile
      phases containing methanol. In the negative ion mode, APPI offered no advantage
      toward APCI. Best results were generally achieved with the dopant chlorobenzene,
      establishing that this dopant is suitable for a wide set of compounds. For one
      quarter of the compounds, significantly better results were achieved with mobile
      phases containing methanol for both APPI and APCI than those with acetonitrile,
      but only in the positive mode. With either of the methods--APPI or APCI--about
      10% of the compounds were not detected. Strategies to get results quickly with
      difficult unknowns will be discussed.

PMID- 25044901
TI  - MALDI-MS analysis and imaging of small molecule metabolites with 1,5
      diaminonaphthalene (DAN).
AB  - 1,5-Diaminonaphthalene (DAN) has previously been reported as an effective matrix
      for matrix-assisted laser desorption ionization-mass spectrometry of
      phospholipids. In the current work, we investigate the use of DAN as a matrix for
      small metabolite analysis in negative ion mode. DAN was found to provide superior
      ionization to the compared matrices for MW < ~400 Da; however, 9-aminoacridine (9
      AA) was found to be superior for a uridine diphosphate standard (MW 566 Da). DAN
      was also found to provide a more representative profile of a natural phospholipid
      mixture than 9-AA. Finally, DAN and 9-AA were applied for imaging of metabolites
      directly from corn leaf sections. Published 2014. This article is a U.S.
      Government work and is in the public domain in the USA.

PMID- 25044902
TI  - Hydrazide and hydrazine reagents as reactive matrices for MALDI-MS to detect
      gaseous aldehydes.
AB  - The reagents 19 hydrazide and 14 hydrazine were examined to function as reactive
      matrices for matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) to detect gaseous aldehydes. Among them, two hydrazide (2
      hydroxybenzohydrazide and 3-hydroxy-2-naphthoic acid hydrazide) and two hydrazine
      reagents [2-hydrazinoquinoline and 2,4-dinitrophenylhydrazine (DNPH)] were found
      to react efficiently with carbonyl groups of gaseous aldehydes (formaldehyde,
      acetaldehyde and propionaldehyde); these are the main factors for sick building
      syndrome and operate as reactive matrices for MALDI-MS. Results from accurate
      mass measurements by JMS-S3000 Spiral-TOF suggested that protonated ion peaks
      corresponding to [M + H](+) from the resulting derivatives were observed in all
      cases with the gaseous aldehydes in an incubation, time-dependent manner. The two
      hydrazide and two hydrazine reagents all possessed absorbances at 337 nm
      (wavelength of MALDI nitrogen laser), with, significant electrical conductivity
      of the matrix crystal and functional groups, such as hydroxy group and amino
      group, being important for desorption/ionization efficiency in MALDI-MS. To our
      knowledge, this is the first report that gaseous molecules could be derivatized
      and detected directly in a single step by MALDI-MS using novel reactive matrices
      that were derivatizing agents with the ability to enhance desorption/ionization
      efficiency.

PMID- 25044903
TI  - Ion internal energy, salt tolerance and a new technical improvement of desorption
      nanoelectrospray.

PMID- 25044904
TI  - Intramolecular oxo-Diels-Alder rearrangement in collisionally activated
      dissociation of protonated ions of a mactrocyclic molecule: triazole-epothilone
      dimer.

PMID- 25044905
TI  - Characterization of a MU-oxo-bridged diiron porphyrin by ESI-LTQ-Orbitrap-MS.

PMID- 25044908
TI  - Development of socioeconomic inequalities in obesity among Dutch pre-school and
      school-aged children.
AB  - OBJECTIVE: To investigate the emergence of the inverse socioeconomic gradient in
      body mass index (BMI) in the first 6 years of life. Furthermore, associations of
      socioeconomic position (SEP) with BMI and total fat mass (%) were assessed at age
      6, and potential mediating factors in the pathway between SEP and children's body
      composition were investigated. METHODS: Nearly 3,656 Dutch children participating
      in a prospective cohort study in Rotterdam, the Netherlands, were included from
      2002 to 2006. Maternal educational level and net household income were used as
      indicators of SEP. BMI and fat mass were both outcome measures. Associations and
      mediation analyses were investigated using linear mixed models and linear
      regression analyses. RESULTS: The lowest SEP groups showed a larger increase in
      BMI over time as compared to the highest SEP groups (P < 0.001), which resulted
      in the emergence of the inverse SEP gradient around 3-4.5 years of age. In 6-year
      old children, both BMI and total fat mass were significantly higher for children
      of low educated mothers (difference in BMI SDS: 0.24; 95% CI 0.15, 0.33; and in
      total fat mass (%): 2.68; 95% CI 2.19, 3.17), which was also shown for children
      with a low household income. This was mainly explained by parental BMI and
      prenatal smoking. CONCLUSIONS: The inverse socioeconomic gradient in obesity
      emerges during the preschool period, and widens with increasing age. A public
      health strategy aimed at tackling the development of inequalities in obesity in
      early childhood needs to start before birth and should include the prevention of
      prenatal smoking and obesity of parents.

PMID- 25044909
TI  - Impact of processing on the bioavailability and vascular effects of blueberry
      (poly)phenols.
AB  - SCOPE: Blueberries are a rich source of flavonoids and phenolic acids. Currently,
      little information is available regarding the impact of processing on the
      bioavailability and the bioactivity of blueberry (poly)phenols. METHODS AND
      RESULTS: In a randomized, controlled crossover trial, ten healthy volunteers
      consumed (a) blueberry-containing baked products, (b) an unprocessed blueberry
      drink containing the same amount of freeze-dried blueberry powder as used in the
      baked products, and (c) matched control baked products. Endothelial function was
      measured as flow-mediated dilation (FMD) and plasma samples taken at baseline and
      at 1, 2, 4, and 6 h postconsumption. Although processing did not significantly
      change the total (poly)phenolic amount, the processed products contained
      significantly less anthocyanins (-42%), more chlorogenic acid (23%), no flavanol
      nonamers or decamers, and significantly more flavanol dimers and trimers (36% and
      28%, respectively). FMD increased after 1, 2, and 6 h consumption of the baked
      products to a similar degree as the unprocessed blueberries, despite significant
      differences in the levels of individual plasma metabolites. No changes were
      observed after the consumption of the control product. CONCLUSION: Careful
      processing can preserve important biological activities of blueberries despite
      changing the blueberry (poly)phenol composition and plasma metabolite profile.

PMID- 25044910
TI  - Ketoprofen enantioseparation with a Cinchona alkaloid based stationary phase:
      enantiorecognition mechanism and release studies.
AB  - With the present contribution, we demonstrate that the baseline separation of
      ketoprofen enantiomers can be successfully achieved (alpha = 1.09; R(S) = 1.60)
      in the reversed-phase mode of elution with a commercially available anion
      exchange-based chiral stationary phase, incorporating the quinine 2,6
      diisopropylphenyl carbamate derivative as the enantioresolving unit. Focused
      modification of the eluent composition indicated a stereoselective role of
      hydrophobic and pi-pi interactions between the selector and selectand units,
      besides the prime ionic intermolecular interaction. The mechanistic hypotheses
      based on the chromatographic data were confirmed by in silico molecular dynamic
      simulations, which allowed us to establish the network of selector-selectand
      interactions underlying the stereorecognition process at a molecular level. The
      validated method was successfully used to evaluate the drug content and release
      profile of ketoprofen-loaded polymeric film, showing drug homogeneous
      distribution into the film and no preferential interactions between the polymer
      and one of the enantiomers, with the racemate released at each time point.

PMID- 25044911
TI  - Thermal methane conversion to formaldehyde promoted by single platinum atoms in
      PtAl2O4 (-) cluster anions.
AB  - Identification and mechanistic study of thermal methane conversion mediated by
      gas-phase species is important for finding potentially useful routes for direct
      methane transformation under mild conditions. Negatively charged oxide species
      are usually inert with methane. This work reports an unexpected result that the
      bi-metallic oxide cluster anions PtAl2 O4 (-) can transform methane into a stable
      organic compound, formaldehyde, with high selectivity. The clusters are prepared
      by laser ablation and reacted with CH4 in an ion trap reactor. The reaction is
      characterized by mass spectrometry and density functional theory calculations. It
      is found that platinum rather than oxygen activates CH4 at the beginning of the
      reaction. The Al2 O4 (-) moiety serves as the support of Pt atom and plays
      important roles in the late stage of the reaction. A new mechanism for selective
      methane conversion is provided and new insights into the surface chemistry of
      single Pt atoms may be obtained from this study. 

PMID- 25044912
TI  - Structural insights into enzymatic degradation of oxidized polyvinyl alcohol.
AB  - The ever-increasing production and use of polyvinyl alcohol (PVA) threaten our
      environment. Yet PVA can be assimilated by microbes in two steps: oxidation and
      cleavage. Here we report novel alpha/beta-hydrolase structures of oxidized PVA
      hydrolase (OPH) from two known PVA-degrading organisms, Sphingopyxis sp. 113P3
      and Pseudomonas sp. VM15C, including complexes with substrate analogues,
      acetylacetone and caprylate. The active site is covered by a lid-like beta
      ribbon. Unlike other esterase and amidase, OPH is unique in cleaving the C?C bond
      of beta-diketone, although it has a catalytic triad similar to that of most
      alpha/beta-hydrolases. Analysis of the crystal structures suggests a double
      oxyanion-hole mechanism, previously only found in thiolase cleaving beta-ketoacyl
      CoA. Three mutations in the lid region showed enhanced activity, with potential
      in industrial applications. 

PMID- 25044914
TI  - Proteomics analysis of adult testis from Bombyx mori.
AB  - The development of the testis involves a large number of tissue-specific
      proteins, possibly because the sperms in it are the most divergent of all cell
      types. In this study, LC-MS/MS was employed to investigate the protein
      compositions of the adult testis of silkworm. A total of 14,431 peptides were
      identified in the adult testis of Bombyx mori, which were matched to 2292
      proteins. Thirty-two HSPs constitute a group of most abundant proteins in the
      adult testis, suggesting that they are critical for the development,
      differentiation, and survival of germ cells. Other proteins in this analysis were
      also involved in testis-specific processes mainly including sperm motility,
      meiosis, germ cell development, and spermatogenesis. The data have been deposited
      to the ProteomeXchange with identifier PXD000909
      (http://proteomecentral.proteomexchange.org/dataset/PXD000909).

PMID- 25044915
TI  - Metric field construction for anisotropic mesh adaptation with application to
      blood flow simulations.
AB  - The goal of this paper is to generate an anisotropic metric field suitable for
      cardiovascular geometries before a fluid simulation. Starting from a curvature
      map, an initial surface metric field is computed. This metric is used for
      anisotropic surface mesh adaptation and consecutively extended inside the volume
      in a frontal manner. The algorithm is based on the method proposed by Alauzet but
      replaces the metric intersection steps by an original metric 'blending'. This
      allows for a graded anisotropic volume mesh with a refinement layer close to the
      walls. The benefits of the resulting mesh are multiple: a reduced number of
      degrees of freedom, a priori refinement in areas with strong gradients of
      velocity and automatically increased resolution in regions with high surface
      curvature. The primal application of this method is in the domain of
      cardiovascular flows. Flow fields and derived quantities (wall shear stress)
      through a model bypass around a stenosed artery obtained on an adapted and
      standard isotropic mesh are compared. In addition, the mesh generation method is
      tested on a more complex patient-specific geometry. Values of computed wall shear
      stress are shown to be close to values obtained on anisotropic Hessian-adapted
      mesh, demonstrating the computational efficiency of the approach in comparison
      with adaptation based on error indicators derived from flow field.

PMID- 25044917
TI  - Future fire emissions associated with projected land use change in Sumatra.
AB  - Indonesia has experienced rapid land use change over the last few decades as
      forests and peatswamps have been cleared for more intensively managed land uses,
      including oil palm and timber plantations. Fires are the predominant method of
      clearing and managing land for more intensive uses, and the related emissions
      affect public health by contributing to regional particulate matter and ozone
      concentrations and adding to global atmospheric carbon dioxide concentrations.
      Here, we examine emissions from fires associated with land use clearing and land
      management on the Indonesian island of Sumatra and the sensitivity of this fire
      activity to interannual meteorological variability. We find ~80% of 2005-2009
      Sumatra emissions are associated with degradation or land use maintenance instead
      of immediate land use conversion, especially in dry years. We estimate Sumatra
      fire emissions from land use change and maintenance for the next two decades with
      five scenarios of land use change, the Global Fire Emissions Database Version 3,
      detailed 1-km2 land use change maps, and MODIS fire radiative power observations.
      Despite comprising only 16% of the original study area, we predict that 37-48% of
      future Sumatra emissions from land use change will occur in fuel-rich peatswamps
      unless this land cover type is protected effectively. This result means that the
      impact of fires on future air quality and climate in Equatorial Asia will be
      decided in part by the conservation status given to the remaining peatswamps on
      Sumatra. Results from this article will be implemented in an atmospheric
      transport model to quantify the public health impacts from the transport of fire
      emissions associated with future land use scenarios in Sumatra.

PMID- 25044916
TI  - Reversible chemical tuning of charge carriers for enhanced photoelectrochemical
      conversion and probing of living cells.
AB  - A facile, solution method for reversible tuning of oxygen vacancies inside TiO2
      nanowires, in which the reducing treatment of TiO2 by NaBH4 leads to 2.4-fold
      increase of photocurrent density, compared to pristine TiO2 nanowires, is
      reported. Subsequent oxidizing treatment using KMnO4 or annealing in air can
      reset the photocurrent density to the original values. The incident photo-to
      current conversion efficiency measurement exhibits that the reduced TiO2
      nanowires present both enhanced photoactivity in both UV and visible regions.
      Density functional theory calculations reveal that the oxygen vacancies in the
      reduced TiO2 cause defect states in the band structure and result in enhanced
      carrier density and conductivity. In addition, the enhanced solar energy-driven
      photoelectrochemical conversion allows real-time, sensitive chemical probing of
      living cells that are directly grown on the TiO2 nanowire photoanodes. As proofs
      of-concept, after functionalized with horseradish peroxidase (HRP) on the
      surface, the reduced TiO2 NWs demonstrate sensitive, real-time monitoring of the
      H2O2 levels in several distinctive living cell lines, with the lowest detectable
      H2O2 concentration of 7.7 nM. This reversible tuning of oxygen vacancies suggests
      a facile means for transition metal oxides, with enhanced photoconversion
      activity and electrochemical sensitivity.

PMID- 25044918
TI  - Conserved nucleation sites reinforce the significance of Phi value analysis in
      protein-folding studies.
AB  - The only experimental strategy to address the structure of folding transition
      states, the so-called Phi value analysis, relies on the synergy between site
      directed mutagenesis and the measurement of reaction kinetics. Despite its
      importance, the Phi value analysis has been often criticized and its power to
      pinpoint structural information has been questioned. In this hypothesis, we
      demonstrate that comparing the Phi values between proteins not only allows
      highlighting the robustness of folding pathways but also provides per se a strong
      validation of the method.

PMID- 25044919
TI  - Palladium-catalyzed amination of aryl sulfides with anilines.
AB  - A combination of a palladium-NHC catalyst and potassium hexamethyldisilazide
      enables the amination of aryl sulfides with anilines to afford a wide variety of
      diarylamines. The reaction conditions are versatile enough for the reaction of
      even bulky ortho-substituted aryl sulfides. This amination can be applied to the
      modular synthesis of N-aryl carbazoles from the corresponding ortho
      bromothioanisoles. As aryl sulfoxides undergo extended Pummerer reactions to
      afford ortho-substituted aryl sulfides, the Pummerer products are thus useful
      substrates for the amination to culminate in efficient syntheses of a 2
      anilinobenzothiophene and an indole as proof-of-principle of the utility of the
      extended Pummerer reaction/amination cascade. 

PMID- 25044920
TI  - A novel approach to monitor clearance of host cell proteins associated with
      monoclonal antibodies.
AB  - Co-purification of a subset of host cell proteins (HCPs) with monoclonal
      antibodies (mAbs) during the capture of mAbs on Protein A affinity chromatography
      is primarily caused by interactions of HCPs with the mAbs. To date, there is
      limited information about the identity of those HCPs due to the difficulty in
      detecting low abundance HCPs in the presence of a large amount of the mAb. Here,
      an approach is presented that allows identification of HCPs that specifically
      associate with the mAb, while avoiding interference from the mAb itself. This
      approach involves immobilization of purified mAb onto chromatography resin via
      cross-linking, followed by incubation with HCPs obtained from supernatant of non
      mAb producer cells that are representative of the expression systems used in mAb
      manufacturing. The HCPs that bind to the mAb are recovered and identified using
      mass spectrometry. This approach has not only allowed a comprehensive comparison
      of HCP subpopulations that associate with different mAbs, but also enabled
      monitoring of the effects of a variety of wash modifiers on the dissociation of
      individual HCP-mAb interactions. The dissociation of HCPs that associated with
      the mAb was monitored by enzyme-linked immunosorbent assay and mass spectrometry.
      This approach can be utilized as a screening tool to assist the development of
      effective and targeted wash steps in Protein A chromatography that ensures not
      only reduction of HCP levels copurified with the mAb but also removal of specific
      HCPs that may have a potential impact on mAb structural stability and patient
      safety.

PMID- 25044921
TI  - Multifunctional organized mesoporous tin oxide films templated by graft
      copolymers for dye-sensitized solar cells.

PMID- 25044922
TI  - Fatigue in patients with advanced renal cell carcinoma receiving sunitinib on an
      intermittent versus continuous dosing schedule in a randomized phase II trial.
AB  - A phase II trial in advanced renal cell carcinoma (RCC) found no benefit in
      efficacy or safety between patients receiving oral sunitinib 50 mg/day for 4
      weeks followed by 2-week off-treatment (Schedule 4/2) and those receiving 37.5 mg
      continuous daily sunitinib. We hypothesized that fatigue would have a more
      variable "on-off" effect with the 4/2 schedule. A total of 292 patients completed
      two fatigue-related items on Days 1 and 29 of each treatment cycle. Mean absolute
      slopes were compared across treatments. A planned analysis of item "I feel
      fatigued" demonstrated that the mean absolute slope was greater in Schedule 4/2
      compared to continuous dosing (0.042 vs. 0.032, P = 0.003), and analysis based on
      the change from Day 1 to Day 29 (0.52 vs. 0.21, P = 0.002) and, separately, Day
      29 to the next Day 1 (-0.38 vs. -0.05, P < 0.001) showed the changes to be
      significantly larger in Schedule 4/2 than continuous dosing. "I have a lack of
      energy" showed a similar pattern graphically, however, the planned analysis was
      not statistically significant based on the absolute slopes but was when Day 1 to
      Day 29 and Day 29 to Day 1 changes were analyzed separately. The 4/2 arm was
      associated with a greater degree of variability in fatigue reflecting a possible
      "on-off" effect whereby patients receiving the 4/2 schedule reported less fatigue
      at the beginning of each cycle compared to Day 29. The findings can inform care
      for individuals with advanced RCC receiving intermittent dosing of sunitinib. 

PMID- 25044923
TI  - Amphiphilic Janus gold nanoparticles prepared by interface-directed self
      assembly: synthesis and self-assembly.
AB  - Materials with Janus structures are attractive for wide applications in materials
      science. Although extensive efforts in the synthesis of Janus particles have been
      reported, the synthesis of sub-10 nm Janus nanoparticles is still challenging.
      Herein, the synthesis of Janus gold nanoparticles (AuNPs) based on interface
      directed self-assembly is reported. Polystyrene (PS) colloidal particles with
      AuNPs on the surface were prepared by interface-directed self-assembly, and the
      colloidal particles were used as templates for the synthesis of Janus AuNPs. To
      prepare colloidal particles, thiol-terminated polystyrene (PS-SH) was dissolved
      in toluene and citrate-stabilized AuNPs were dispersed in aqueous solution. Upon
      mixing the two solutions, PS-SH chains were grafted to the surface of AuNPs and
      amphiphilic AuNPs were formed at the liquid-liquid interface. PS colloidal
      particles decorated with AuNPs on the surfaces were prepared by adding the
      emulsion to excess methanol. On the surface, AuNPs were partially embedded in the
      colloidal particles. The outer regions of the AuNPs were exposed to the solution
      and were functionalized through the grafting of atom-transfer radical
      polymerization (ATRP) initiator. Poly[2-(dimethamino)ethyl methacrylate]
      (PDMAEMA) on AuNPs were prepared by surface-initiated ATRP. After centrifugation
      and dissolving the colloidal particles in tetrahydrofuran (THF), Janus AuNPs with
      PS and PDMAEMA on two hemispheres were obtained. In acidic pH, Janus AuNPs are
      amphiphilic and are able to emulsify oil droplets in water; in basic pH, the
      Janus AuNPs are hydrophobic. In mixtures of THF/methanol at a volume ratio of
      1:5, the Janus AuNPs self-assemble into bilayer structures with collapsed PS in
      the interiors and solvated PDMAEMA at the exteriors of the structures. 

PMID- 25044924
TI  - Luminescent cyclometalated platinum(II) complex forms emissive intercalating
      adducts with double-stranded DNA and RNA: differential emissions and anticancer
      activities.
AB  - Luminescent metallo-intercalators are potent biosensors of nucleic acid structure
      and anticancer agents targeting DNAs. There are few examples of luminescent
      metallo-intercalators which can simultaneously act as emission probes of nucleic
      acid structure and display promising anticancer activities. Herein, we describe a
      luminescent platinum(II) complex, [Pt(C^N^N)(C=NtBu)]ClO4 (1 a, HC^N^N= 6-phenyl
      2,2'-bipyridyl), that intercalates between the nucleobases of nucleic acids,
      accompanied by an increase in emission intensity and/or a significant change in
      the maximum emission wavelength. The changes in emission properties measured with
      double-stranded RNA (dsRNA) are different from those with dsDNA used in the
      binding reactions. Complex 1 a exhibited potent anticancer activity towards
      cancer cells in vitro and inhibited tumor growth in a mouse model. The
      stabilization of the topoisomerase I-DNA complex with resulting DNA damage by 1 a
      is suggested to contribute to its anticancer activity.

PMID- 25044925
TI  - Low temperature hydrogen reduction of high surface area anatase and anatase/beta
      TiO2 for high-charging-rate batteries.
AB  - There are several strategies to improve the electrochemical performance of TiO2
      as negative electrode material for Li-ion batteries. Introducing oxygen vacancies
      through hydrogen reduction leads to an enhancement in electrical conductivity.
      However, this strategy does not improve the low lithium-ion mobility. Herein, we
      show that by decreasing the temperature of hydrogen annealing the improved
      lithium-ion mobility of high-surface-area TiO2 and beta-TiO2 can be combined with
      the enhanced electrical conductivity of oxygen deficiencies. Annealing at only
      275-300  degrees C in pure hydrogen atmosphere successfully creates oxygen
      vacancies in TiO2, as confirmed by UV/Vis spectroscopy, whereas the temperature
      is low enough to maintain a high specific surface area and prevent beta-to
      anatase phase transformation. The hydrogen reduction of high-surface-area anatase
      or anatase/beta-TiO2 at these temperatures leads to improvements in the
      performance, achieving charge capacities of 142 or 152 mAh g(-1) at 10C,
      respectively.

PMID- 25044926
TI  - Selective ortho-hydroxylation-defluorination of 2-fluorophenolates with a bis(MU
      oxo)dicopper(III) species.
AB  - The bis(MU-oxo)dicopper(III) species [Cu(III) 2 (MU-O)2 (m-XYL(MeAN) )](2+) (1)
      promotes the electrophilic ortho-hydroxylation-defluorination of 2
      fluorophenolates to give the corresponding catechols, a reaction that is not
      accomplishable with a (eta(2) :eta(2) -O2 )dicopper(II) complex. Isotopic
      labeling studies show that the incoming oxygen atom originates from the bis(MU
      oxo) unit. Ortho-hydroxylation-defluorination occurs selectively in
      intramolecular competition with other ortho-substituents such as chlorine or
      bromine. 

PMID- 25044928
TI  - Learning and memory performance in a cohort of clinically referred breast cancer
      survivors: the role of attention versus forgetting in patient-reported memory
      complaints.
AB  - OBJECTIVE: While forgetfulness is widely reported by breast cancer survivors,
      studies documenting objective memory performance yield mixed, largely
      inconsistent, results. Failure to find consistent, objective memory issues may be
      due to the possibility that cancer survivors misattribute their experience of
      forgetfulness to primary memory issues rather than to difficulties in attention
      at the time of learning. METHODS: To clarify potential attention issues, factor
      scores for Attention Span, Learning Efficiency, Delayed Memory, and Inaccurate
      Memory were analyzed for the California Verbal Learning Test-Second Edition (CVLT
      II) in 64 clinically referred breast cancer survivors with self-reported
      cognitive complaints; item analysis was conducted to clarify specific
      contributors to observed effects, and contrasts between learning and recall
      trials were compared with normative data. Performance on broader cognitive
      domains is also reported. RESULTS: The Attention Span factor, but not Learning
      Efficiency, Delayed Memory, or Inaccurate Memory factors, was significantly
      affected in this clinical sample. Contrasts between trials were consistent with
      normative data and did not indicate greater loss of information over time than in
      the normative sample. CONCLUSIONS: Results of this analysis suggest that
      attentional dysfunction may contribute to subjective and objective memory
      complaints in breast cancer survivors. These results are discussed in the context
      of broader cognitive effects following treatment for clinicians who may see
      cancer survivors for assessment.

PMID- 25044929
TI  - Cataluminescence-based sensors: principle, instrument and application.
AB  - The cataluminescence (CTL)-based sensor is a new promising type of chemical
      transducer, and has attracted much attention of researchers for its potential
      versatile applications in public safety, emission control and environmental
      protection. In this review, we briefly introduce the development history of CTL
      based sensors and summarize existing explanations of the CTL reaction mechanism
      as well as three research strategies for mechanism the CTL mechanism. In the
      following, all the function units of a typical CTL-based sensor system are
      described and the investigation of the sensor materials. CTL-based sensor arrays,
      are discussed in detail. We classify the recent novel hyphenated techniques based
      on CTL coupled to other analysis techniques into the preconcentration-CTL
      hyphenated technique, nebulization-CTL hyphenated technique, plasma-assisted CTL
      technique and tandem CTL technique according to the type of analysis combined
      with CTL and provide a detailed account of novel hyphenated techniques. Owing to
      the appearance of these novel techniques, the application range of CTL has been
      expanded as well as the sensitivity and selectivity of CTL system has been
      greatly improved. Finally, the applications of CTL-based sensor and sensor arrays
      in the last several years are classified and summarized.

PMID- 25044927
TI  - Membrane potential-dependent integration of synaptic inputs in entorhinal
      stellate neurons.
AB  - Stellate cells (SCs) of the medial entorhinal cortex exhibit robust spontaneous
      membrane-potential oscillations (MPOs) in the theta (4-12 Hz) frequency band as
      well as theta-frequency resonance in their membrane impedance spectra. Past
      experimental and modeling work suggests that these features may contribute to the
      phase-locking of SCs to the entorhinal theta rhythm and may be important for
      forming the hexagonally tiled grid cell place fields exhibited by these neurons
      in vivo. Among the major biophysical mechanisms contributing to MPOs is a
      population of persistent (non-inactivating or slowly inactivating) sodium
      channels. The resulting persistent sodium conductance (GNaP ) gives rise to an
      apparent increase in input resistance as the cell approaches threshold. In this
      study, we used dynamic clamp to test the hypothesis that this increased input
      resistance gives rise to voltage-dependent, and thus MPO phase-dependent, changes
      in the amplitude of excitatory and inhibitory post-synaptic potential (PSP)
      amplitudes. We find that PSP amplitude depends on membrane potential, exhibiting
      a 5-10% increase in amplitude per mV depolarization. The effect is larger than
      and sums quasi-linearly with-the effect of the synaptic driving force, V - Esyn .
      Given that input-driven MPOs 10 mV in amplitude are commonly observed in MEC
      stellate cells in vivo, this voltage- and phase-dependent synaptic gain is large
      enough to modulate PSP amplitude by over 50% during theta-frequency MPOs. Phase
      dependent synaptic gain may therefore impact the phase locking and phase
      precession of grid cells in vivo to ongoing network oscillations. (c) 2014 Wiley
      Periodicals, Inc. 

PMID- 25044930
TI  - BN-phenanthryne: cyclotetramerization of an 1,2-azaborine derivative.
AB  - Thermolysis of 9-azido-9-borafluorene in heptane solution produces the tetramer
      of a BN-phenanthryne. The isolation of the self-trapping product provides
      evidence for the involvement of the BN-aryne in the thermolysis reaction. Its
      formation may be rationalized by denitrogenation of the azide and ring
      enlargement. 

PMID- 25044931
TI  - Pancreatic neuroendocrine tumors: accurate grading with Ki-67 index on fine
      needle aspiration specimens using the WHO 2010/ENETS criteria.
AB  - BACKGROUND: The natural history of pancreatic neuroendocrine tumors (panNETs) is
      extremely variable. One of the most controversial problems in diagnosis is the
      accurate prediction of the clinical behavior of these tumors. PanNETs that behave
      aggressively with a malignant course may have bland cytologic features, while
      some tumors with previously described "malignant" features may behave in a benign
      or indolent fashion. Various classification schemes have been proposed for
      grading panNETs. The European Neuroendocrine Tumor Society (ENETS) and 2010 World
      Health Organization (WHO) classification schemes include counting the mitotic
      index and/or the Ki-67 proliferation index for grading. The current study was
      undertaken to determine whether tumors sampled by endoscopic ultrasound-guided
      fine-needle aspiration (EUS-FNA) can be accurately graded based on the Ki-67
      index when compared to surgical samples. METHODS: Corresponding EUS-FNA cytology
      and surgical tissue specimens were obtained for 22 tumors and stained for
      hematoxylin and eosin (H&E) and the Ki-67 proliferation marker (MIB-1 antibody).
      Samples were graded by scoring Ki-67 staining indices in accordance with the 2010
      ENETS/WHO criteria. The grading scores assigned to the EUS-FNA cytology samples
      were compared with the scores assigned to the corresponding histological samples.
      RESULTS: The majority (86%) of EUS-FNA cytology samples and corresponding
      surgical tissue specimens demonstrated concordant grading based on Ki-67 indices.
      CONCLUSIONS: These results indicate that EUS-FNA cytology samples can be
      accurately graded based on the WHO Ki-67 labeling scheme. Thus, Ki-67 scoring in
      EUS-FNA cytology samples is an alternative approach for establishing the grade of
      panNETs. Accurate grading of panNETs is critical for predicting tumor biology,
      patient prognosis, and making informed decisions regarding patient management and
      treatment.

PMID- 25044932
TI  - Adult stem cells in the knifefish cerebellum.
AB  - Adult neurogenesis has been described in dozens of brain regions in teleost fish,
      with the largest number of new neurons being generated in the cerebellum. Here,
      we characterized the cerebellar neural stem/progenitor cells (NSPCs) in the brown
      ghost knifefish (Apteronotus leptorhynchus), an established model system of adult
      neurogenesis. The majority of the new cerebellar cells arise from neurogenic
      niches located medially, at the interface of the dorsal/ventral molecular layers
      and the granular layer. NSPCs within these niches give rise to transit-amplifying
      progenitors which populate the molecular layer, where they continue to
      proliferate during their migration toward target areas in the granular layer. At
      any given time, the majority of proliferating cells are located in the molecular
      layer. Immunohistochemical staining revealed that the stem cell markers Sox2,
      Meis1/2/3, Islet1, and, to a lesser extent, Pax6, are widely expressed in all
      regions of the adult cerebellum. A large subpopulation of these NSPCs coexpress
      S100, GFAP, and/or vimentin, indicating astrocytic identity. This is further
      supported by the specific effect of the gliotoxin l-methionine sulfoximine, which
      leads to a targeted decrease in the number of GFAP+ cells that coexpress Sox2 or
      the proliferation marker PCNA. Pulse-chase analysis of the label size associated
      with new cells after administration of 5-bromo-2'-deoxyuridine demonstrated that,
      on average, two additional cell divisions occur after completion of the initial
      mitotic cycle. Overall numbers of NSPCs in the cerebellum niches increase
      consistently over time, presumably in parallel with the continuous growth of the
      brain.

PMID- 25044933
TI  - Functional analyses of mutations in HEPACAM causing megalencephalic
      leukoencephalopathy.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type
      of leukodystrophy characterized by white matter edema. Autosomal-recessive
      mutations in MLC1 cause MLC type 1, and autosomal-recessive or dominant mutations
      in HEPACAM (also called GLIALCAM) cause MLC type 2A and type 2B, respectively.
      The role of MLC1 and HEPACAM is unknown, although they have been related with the
      processes of cell-volume regulation and potassium siphoning by astrocytes.
      Previous studies with some of the mutations identified in HEPACAM showed that
      most of them are associated with a trafficking defect. Here, we analyzed
      biochemically and functionally most mutations identified up-to-date in HEPACAM.
      Our results allow classifying the effect of mutations in different subtypes and
      we indicate different cellular mechanisms that lead to MLC pathogenesis. 

PMID- 25044934
TI  - Isoflurane induces dose-dependent alterations in the cortical connectivity
      profiles and dynamic properties of the brain's functional architecture.
AB  - Despite their widespread use, the effect of anesthetic agents on the brain's
      functional architecture remains poorly understood. This is particularly true of
      alterations that occur beyond the point of induced unconsciousness. Here, we
      examined the distributed intrinsic connectivity of macaques across six isoflurane
      levels using resting-state functional MRI (fMRI) following the loss of
      consciousness. The results from multiple analysis strategies showed stable
      functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as
      a suitable range for anesthetized nonhuman primate resting-state investigations.
      Dose-dependent effects were evident at moderate to high dosages showing
      substantial alteration of the functional topology and a decrease or complete loss
      of interhemispheric cortical FC strength including that of contralateral
      homologues. The assessment of dynamic FC patterns revealed that the functional
      repertoire of brain states is related to anesthesia depth and most strikingly,
      that the number of state transitions linearly decreases with increased isoflurane
      dosage. Taken together, the results indicate dose-specific spatial and temporal
      alterations of FC that occur beyond the typically defined endpoint of
      consciousness. Future work will be necessary to determine how these findings
      generalize across anesthetic types and extend to the transition between
      consciousness and unconsciousness.

PMID- 25044935
TI  - A prospective comparison of MRI-US fused targeted biopsy versus systematic
      ultrasound-guided biopsy for detecting clinically significant prostate cancer in
      patients on active surveillance.
AB  - BACKGROUND: In active surveillance (AS) patients: (i) To compare the ability of a
      multiparametric MRI (mpMRI)-ultrasound biopsy system to detect clinically
      significant (CS) prostate cancer with systematic 12-core biopsy (R-TRUSBx), and
      (ii) To assess the predictive value of mpMRI with biopsy as the reference
      standard. METHODS: Seventy-two men on AS prospectively underwent 3T mpMRI . MRI
      ultrasound fusion biopsy (UroNavBx) and R-TRUSBx was performed. CS cancer was
      defined using two thresholds: 1) GS >= 7 (CS7) and 2) GS = 6 with >50%
      involvement (GS6). CS cancer detection rates and predictive values were
      determined. RESULTS: CS7 cancers were found in 19/72 (26%), 7 (37%) identified by
      UroNavBx alone, 2 (11%) by R-TRUSBx alone (P = 0.182). UroNav targeted biopsy was
      6.3* more likely to yield a core positive for CS7 cancer compared with R-TRUSBx
      (25% of 141 versus 4% of 874, P < 0.001). Upgrading of GS occurred in 15/72
      patients (21%), 13 (87%) detected by UroNavBx and 10 (67%) by R-TRUSBx. The NPV
      of mpMRI for CS7 cancer was 100%. MRI suspicion level significantly predicted CS
      cancer on multivariate analysis (OR 3.6, P < 0.001). CONCLUSION: UroNavBx
      detected CS cancer with far fewer cores compared with R-TRUSBx, and mpMRI had a
      perfect negative predictive value in this population.

PMID- 25044936
TI  - The homeodomain transcription factor PITX2 is required for specifying correct
      cell fates and establishing angiogenic privilege in the developing cornea.
AB  - BACKGROUND: Correct specification of cell lineages and establishing angiogenic
      privilege within the developing cornea are essential for normal vision but the
      mechanisms controlling these processes are poorly understood. RESULTS: We show
      that the homeodomain transcription factor PItX2 is expressed in mesenchymal cells
      of the developing and mature cornea and use a temporal gene knockout approach to
      demonstrate that PITX2 is required for corneal morphogenesis and the
      specification of cell fates within the surface ectoderm and mesenchymal
      primordia. PITX2 is also required to establish angiogenic privilege in the
      developing cornea. Further, the expression of Dkk2 and suppression of canonical
      Wnt signaling activity levels are key mechanisms by which PITX2 specifies ocular
      surface ectoderm as cornea. In contrast, specifying the underlying mesenchyme to
      corneal fates and establishing angiogenic privilege in the cornea are less
      sensitive to DKK2 activity. Finally, the cellular expression patterns of FOXC2,
      PITX1, and BARX2 in Pitx2 and Dkk2 mutants suggest that these transcription
      factors may be involved in specifying cell fate and establishing angiogenic
      privilege within the corneal mesenchyme. However, they are unlikely to play a
      role in specifying cell fate within the corneal ectoderm. CONCLUSIONS: Together,
      these data provide important insights into the mechanisms regulating cornea
      development.

PMID- 25044937
TI  - Gene expression profile analysis of SUDHL6 cells with siRNA-mediated BCL11A
      downregulation.
AB  - Our previous study has shown that downregulation of B-cell chronic lymphocytic
      leukemia (CLL)/lymphoma11A (BCL11A) gene by small interfering RNA (siRNA)
      resulted in the growth inhibition and apoptosis of B cell lymphoma cell line
      SUDHL6. To gain further insight into the molecular mechanisms of this process and
      identify the differentially expressed genes in SUDHL6 cells after BCL11A
      downregulation, the global gene expression profile was identified and analyzed
      using the Affymetrix HG-U133 Plus 2.0 array. Twenty-one differentially expressed
      genes were validated and analyzed from the BCL11A siRNA-treated SUDHL6 cells.
      There was a significant dysregulation in the global gene expression of the BCL11A
      suppressed SUDHL6 cells. There were 1903 genes differentially expressed with >2
      fold changes between the BCL11A siRNA- and negative control-transfected cells. Of
      these, there were 916 upregulated genes and 987 downregulated genes. The
      differential genes are involved in various molecular functions and signaling
      pathways. QRT-PCR validation of the selected differentially expressed genes
      demonstrated there was a good correlation with the microarray analysis. There was
      a significant deregulation of expression in the apoptosis-related genes such as
      BCL-2, BCL2L11 and involved in TGFbeta, MAPK, WNT signaling pathways after BCL11A
      was downregulated in SUDHL6 cells. Our results show that the suppression of
      BCL11A by RNA interference altered gene expression profile of SUDHL6 cells. The
      apoptosis-related genes BCL-2, BCL2L11 and the gene alterations in TGFbeta, MAPK,
      WNT signaling pathways might be important in BCL11A siRNA-induced apoptosis of
      SUDHL6 cells, suggesting BCL11A is involved in gene networks associated with
      apoptosis. 

PMID- 25044938
TI  - Benzocyclobutane, benzocycloheptane and heptene derivatives as melatonin agonists
      and antagonists.
AB  - Two series of analogues were designed, synthesised and evaluated as potential
      human melatonin type 1 and 2 receptor (hMT1 and hMT2 ) ligands. Their biological
      effects were assessed by a well-established, specific model of melatonin action,
      the pigment response of Xenopus laevis melanophores. Compounds containing a
      benzocyclobutane scaffold and a methoxy group in the "melatonin" orientation were
      found to be potent agonists, with one of the analogues exhibiting activity
      comparable to melatonin. In contrast, analogues with a methoxy group in non
      melatonin positions or with multiple methoxy groups showed either weaker agonist
      activity or were antagonists. Benzocycloheptene derivatives with one methoxy
      group are found to be weak agonists, whereas those with two methoxy groups were
      found to be antagonists, as were all of the benzocycloheptane derivatives
      evaluated. The most active compounds were assessed in a human receptor radio
      ligand binding assay but showed little discrimination between MT1 and MT2 . These
      results again show that the indole nitrogen of melatonin is not a necessary
      component for analogue activity and also illustrate that replacement of the
      indole ring with a 4-membered carbocycle can provide highly active compounds when
      the methoxy group is in the melatonin position. 

PMID- 25044942
TI  - Modulation of mouse macrophage polarization in vitro using IL-4 delivery by
      osmotic pumps.
AB  - Modulation of macrophage polarization is emerging as promising means to mitigate
      wear particle-induced inflammation and periprosthetic osteolysis. As a model for
      continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4
      in order to modulate macrophage polarization in vitro from nonactivated M0 and
      inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps
      delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media.
      This conditioned media (CM) was collected at seven day intervals up to four weeks
      (week 1 to week 4 samples). IL-4 concentration in the CM was determined by ELISA
      and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or
      week 4 CM. The IL-4 concentration in the CM approximated the mathematically
      calculated amount, and its biological activity was well retained, as both M0 and
      M1 macrophages exposed to either the week 1 or week 4 CM assumed M2-like
      phenotype as determined by qRT-PCR, ELISA, and immunocytochemistry. The results
      show that IL-4 can be delivered using osmotic pumps and that IL-4 delivered can
      modulate macrophage phenotype. Results build a foundation for in vivo studies
      using our previously validated animal models and provide possible strategies to
      locally mitigate wear particle-induced macrophage activation and periprosthetic
      osteolysis.

PMID- 25044943
TI  - Macromolecule loading into spherical, elliptical, star-like and cubic calcium
      carbonate carriers.
AB  - We fabricated calcium carbonate particles with spherical, elliptical, star-like
      and cubical morphologies by varying relative salt concentrations and adding
      ethylene glycol as a solvent to slow down the rate of particle formation. The
      loading capacity of particles of different isotropic (spherical and cubical) and
      anisotropic (elliptical and star-like) geometries is investigated, and the
      surface area of such carriers is analysed. Potential applications of such drug
      delivery carriers are highlighted. 

PMID- 25044944
TI  - Flow cytometry of ALK-negative anaplastic large cell lymphoma of breast implant
      associated effusion and capsular tissue.
AB  - BACKGROUND: Anaplastic large cell lymphoma (ALCL) of the breast capsule is a rare
      lymphoma involving capsular tissues and/or effusions associated with breast
      implants. While several studies have detailed the histological and
      immunohistochemical (IHC) features of these tumors, no study has yet described
      flow cytometry features of the neoplastic cells of this entity. Here, we report
      two cases from our institution in which multi-parametric flow cytometry was
      performed. METHODS: The immunophenotype of ALCL in association with breast
      implant was evaluated by flow cytometry. RESULTS: We show that much like CD30+
      tumor cells of classical Hodgkin lymphoma (CHL) and ALCL of non-breast implant
      tumors, the neoplastic cells of this entity can be readily identified by flow
      cytometry. The neoplastic cells of both cases were largely devoid of T-cell
      antigens, but had expression of weak CD15, strong CD30, and expression of CD40.
      These results are correlated with routine morphologic and IHC analysis,
      supporting the flow cytometry immunophenotype. CONCLUSIONS: Flow cytometry can
      aid in the diagnostic evaluation of effusions or tissue samples in association
      with breast implant/prostheses.

PMID- 25044945
TI  - Spread of X inactivation on chromosome 15 is associated with a more severe
      phenotype in a girl with an unbalanced t(X; 15) translocation.
AB  - We report on a baby girl with multiple congenital abnormalities, including cleft
      palate, intrauterine growth restriction, and double outlet right ventricle (DORV)
      with ventricular septal defect. She had an unbalanced chromosome translocation t
      (X;15) resulting in monosomy 15pter -> p10 and trisomy Xq13.1 -> q28. All three
      copies of Xq encompass the XIST gene. It is known that X chromosome inactivation
      could spread to the autosome part of an unbalanced translocation involving
      chromosome X and an autosome. To confirm the spread of X chromosome inactivation
      on chromosome 15, we evaluate the methylation change by the HumanMethylation450
      BeadChip, a whole genome DNA methylation micorarray that includes 15,259 probes
      spanning 717 genes on chromosome 15. Results showed there was gain in DNA
      methylation of more than 20% in 586 CpG sites spanning the long arm of chromosome
      15. We further examined the hypermethylated CpG sites located in CpG-island
      promoter, because genes subjected to X chromosome inactivation will have an
      increase in DNA methylation level in this region. A total of 75 sites
      representing 24 genes were hypermethylated. Nearly all of these probes are
      located in region proximal to the breakpoint, from 15q11.2 to 15q21.3 (35Mb)
      suggesting that X inactivation was spread to the proximal region of 15q. Gain of
      DNA methylation, especially in the CpG-island promoter, can result in functional
      inactivation of genes, and therefore could potentially worsen the phenotype of
      our patient.

PMID- 25044946
TI  - Undergraduates improve upon published crystal structure in class assignment.
AB  - Recently, 57 undergraduate students at the University of Michigan were assigned
      the task of solving a crystal structure, given only the electron density map of a
      1.3 A crystal structure from the electron density server, and the position of the
      N-terminal amino acid. To test their knowledge of amino acid chemistry, the
      students were not given the protein sequence. With minimal direction from the
      instructor on how the students should complete the assignment, the students fared
      remarkably well in this task, with over half the class able to reconstruct the
      original sequence with over 77% sequence identity, and with structures whose
      median ranked in the 91(st) percentile of all structures of comparable resolution
      in terms of structure quality. Fourteen percent of the students' structures
      produced Molprobity steric clash validation scores even better than that of the
      original structure, suggesting that multiple students achieved an improvement in
      the overall structure quality compared to the published structure. Students were
      able to delineate limiting case chemical environments, such as charged
      interactions or complete solvent exposure, but were less able to distinguish
      finer details of hydrogen bonding or hydrophobicity. Our results prompt several
      questions: why were students able to perform so well in their structural
      validation scores? How were some students able to outperform the 88% sequence
      identity mark that would constitute a perfect score, given the level of
      degenerate density or surface residues with poor density? And how can the
      methodology used by the best students inform the practices of professional X-ray
      crystallographers?

PMID- 25044947
TI  - Preparation of the first manganese(III) and manganese(IV) azides.
AB  - Fluoride-azide exchange reactions of Me3SiN3 with MnF2 and MnF3 in acetonitrile
      resulted in the isolation of Mn(N3)2 and Mn(N3)3 ?CH3CN, respectively. While
      Mn(N3)2 forms [PPh4]2[Mn(N3)4] and (bipy)2Mn(N3)2 upon reaction with PPh4N3 and
      2,2'-bipyridine (bipy), respectively, the manganese(III) azide undergoes
      disproportionation and forms mixtures of [PPh4]2[Mn(N3)4] and [PPh4]2[Mn(N3)6],
      as well as (bipy)2Mn(N3)2 and (bipy)Mn(N3)4. Neat and highly sensitive
      Cs2[Mn(N3)6] was obtained through the reaction of Cs2MnF6 with Me3SiN3 in CH3CN.

PMID- 25044948
TI  - Docosahexaenoic acid reduces linoleic acid induced monocyte chemoattractant
      protein-1 expression via PPARgamma and nuclear factor-kappaB pathway in retinal
      pigment epithelial cells.
AB  - SCOPE: To investigate whether docosahexaenoic acid (DHA) could inhibit linoleic
      acid (LA) induced monocyte chemoattractant protein (MCP)-1 expression in human
      retinal pigment epithelial (RPE) cells. METHODS AND RESULTS: ARPE-19 cells were
      pretreated with DHA and then exposed to LA. The expression of MCP-1 and PPARgamma
      was examined using RT-PCR and Western blot analysis. LA at 10, 25, or 50 MUM
      induced expression of MCP ARPE-19 cells in a dose-dependent manner (p < 0.05).
      DHA at 50 and 100 MUM effectively inhibited LA-induced MCP-1 expression and
      production (p < 0.05) and NF-kappaB activation. In addition, the culture medium
      from LA-stimulated ARPE-19 cells could induce tube formation in choroidal
      endothelial cells (RF6A), whereas 100 MUM DHA inhibited tube formation. DHA at
      100 MUM increased the expression and activity of PPARgamma (p < 0.05).
      Pretreatment with PPARgamma inhibitor (GW9662) abolished the inhibitory effect of
      DHA (100 MUM) on LA-induced IkappaB degradation, p65 translocation, and MCP-1
      expression in ARPE-19 cells (p < 0.05), as well as tube formation in RF6A.
      CONCLUSION: DHA reduced LA-induced MCP-1 expression via a PPARgamma- and NF
      kappaB-dependent pathway in ARPE-19 cells. These results suggest the molecular
      mechanisms underlying the beneficial effects of increased consumption of DHA and
      reduced consumption of LA on age-related macular degeneration.

PMID- 25044949
TI  - Auditory temporal processing skills in musicians with dyslexia.
AB  - The core cognitive difficulty in developmental dyslexia involves phonological
      processing, but adults and children with dyslexia also have sensory impairments.
      Impairments in basic auditory processing show particular links with phonological
      impairments, and recent studies with dyslexic children across languages reveal a
      relationship between auditory temporal processing and sensitivity to rhythmic
      timing and speech rhythm. As rhythm is explicit in music, musical training might
      have a beneficial effect on the auditory perception of acoustic cues to rhythm in
      dyslexia. Here we took advantage of the presence of musicians with and without
      dyslexia in musical conservatoires, comparing their auditory temporal processing
      abilities with those of dyslexic non-musicians matched for cognitive ability.
      Musicians with dyslexia showed equivalent auditory sensitivity to musicians
      without dyslexia and also showed equivalent rhythm perception. The data support
      the view that extensive rhythmic experience initiated during childhood (here in
      the form of music training) can affect basic auditory processing skills which are
      found to be deficient in individuals with dyslexia.

PMID- 25044950
TI  - Impact of the prorenin/renin receptor on the development of obesity and
      associated cardiometabolic risk factors.
AB  - OBJECTIVE: Obesity is a worldwide epidemic and current treatments have limited
      success thus, novel therapies are warranted. Our objective was to determine
      whether the prorenin/renin receptor [(P)RR] is implicated in obesity. METHODS:
      Mice received a normal or high-fat/high-carbohydrate diet with the handle region
      peptide (HRP), a (P)RR blocker, or saline for 10 weeks. Post-menopausal non
      diabetic obese women were enrolled in the Complication Associated with Obesity
      Study and were classified as insulin-resistant (IRO) or -sensitive (ISO) using a
      hyperinsulinemic-euglycemic clamp. RESULTS: In mice, obesity increased the (P)RR
      by twofold in adipose tissue. Likewise, renin increased by at least twofold. The
      HRP reduced weight gain in obese mice by 20% associated to a 19% decrease in
      visceral fat. This was accompanied by a 48% decrease in leptin mRNA in fat and
      33% decrease in circulating leptin. Inflammatory markers were also decreased by
      the HRP treatment. HRP normalized triglyceridemia and reduced insulinemia by 34%
      in obese mice. Interestingly, we observed a 33% increase in (P)RR mRNA in the fat
      of IRO women compared to ISO. CONCLUSIONS: This is the first report of a
      potential implication in obesity of the (P)RR which may be a novel therapeutic
      target.

PMID- 25044951
TI  - Chemical interaction between Paeonia lactiflora and Glycyrrhiza uralensis, the
      components of Jakyakgamcho-tang, using a validated high-performance liquid
      chromatography method: herbal combination and chemical interaction in a
      decoction.
AB  - The herbal combination is the basic unit of a herbal formula that affects the
      chemical characteristics of individual herbs. In the present study, a method of
      simultaneous determination of the 11 marker compounds in Jakyakgamcho-tang was
      developed using high-performance liquid chromatography with photodiode array
      detection. The validated analytical method was successfully applied to approach
      the chemical interaction between Paeonia lactiflora and Glycyrrhiza uralensis in
      co-decoction. In P. lactiflora, the contents of gallic acid, oxypaeoniflorin, (+)
      catechin, paeoniflorin, and benzoylpaeoniflorin were decreased, while those of
      albiflorin and benzoic acid were increased; in G. uralensis, the contents of
      liquiritin, isoliquiritin, ononin, and glycyrrhizin were decreased, when
      decocting two herbs together. Moreover, as the ratio between P. lactiflora and G.
      uralensis was increased, the contents of chemical contents from each herb were
      proportionally increased. However, each content of marker compound per the gram
      of herbal medicine was decreased as the ratio of combinative herbs increased. The
      results showed that P. lactiflora and G. uralensis affect the extraction
      efficiency of chemical compounds in a Jakyakgamcho-tang decoction. Overall, the
      method established in this study was simple, rapid, and accurate, and would be
      useful for the determination of marker compounds and for the investigation of the
      chemical interaction between herbal medicines. 

PMID- 25044952
TI  - Cyclizing radical carboiodination, carbotelluration, and carboaminoxylation of
      aryl amines.
AB  - Radical carboiodination of various aryl amines is reported. Aryl diazonium salts,
      generated in situ from the corresponding aryl amines, are reacted with Bu4NI to
      provide the corresponding aryl radicals which undergo 5-exo or 6-exo cyclization.
      Iodine abstraction eventually affords the carboiodinated products in good to
      excellent yields. If TEMPO is added, the cascade provides the cyclized
      carboaminoxylation products. Running the reaction in the presence of PhTeTePh
      affords the phenyltellurated cyclized products.

PMID- 25044953
TI  - Three acyltetronic acid derivatives: noncanonical cryptic polyketides from
      Aspergillus niger identified by genome mining.
AB  - Induced production of tetronate derivatives: We activated a dormant PKS-NRPS gene
      cluster in Aspergillus niger ATCC 1015 by expressing its dedicated transcription
      activator (caaR). As a result, the transformant expressing caaR produces three
      acyltetronate derivatives: carlosic acid (1), agglomerin F (2), and carlosic acid
      methyl ester (3). 

PMID- 25044954
TI  - High performance of a palladium phosphinooxazoline catalyst in the asymmetric
      arylation of cyclic N-sulfonyl ketimines.
AB  - A cationic palladium complex with a chiral phosphine-oxazoline ligand (iPr-phox)
      showed high catalytic activity and enantioselectivity in the asymmetric addition
      of arylboronic acids to six-membered cyclic N-sulfonyl ketimines to give high
      yields of the corresponding chiral cyclic sulfamidates with 96-99.9% ee. The
      products have tetrasubstituted stereogenic centers with an amino group and a
      triaryl or alkyldiaryl group as substituents.

PMID- 25044955
TI  - Surface modification of solid-state nanopores for sticky-free translocation of
      single-stranded DNA.
AB  - Nanopore technology is one of the most promising approaches for fast and low-cost
      DNA sequencing application. Single-stranded DNA detection is primary objective in
      such device, while solid-state nanopores remain less explored than their
      biological counterparts due to bio-molecule clogging issue caused by surface
      interaction between DNA and nanopore wall. By surface coating a layer of
      polyethylene glycol (PEG), solid-state nanopore can achieve long lifetime for
      single-stranded DNA sticky-free translocation at pH 11.5. Associated with
      elimination of non-specific binding of molecule, PEG coated nanopore presents new
      surface characteristic as less hydrophility, lower 1/f noise, and passivated
      surface charge responsiveness on pH. Meanwhile, conductance blockage of single
      stranded DNA is found to be deeper than double-stranded DNA, which can be well
      described by a string of blobs model for a quasi-equilibrium state polymer in
      constraint space. 

PMID- 25044956
TI  - Tunneling assists the 1,2-hydrogen shift in N-heterocyclic carbenes.
AB  - At room temperature, 1,2-hydrogen-transfer reactions of N-heterocyclic carbenes,
      like the imidazol-2-ylidene to give imidazole is shown to occurr almost entirely
      (>90 %) by quantum mechanical tunneling (QMT). At 60 K in an Ar matrix, for the
      2, 3-dihydrothiazol-2-ylidene->thiazole transformation, QMT is shown to increase
      the rate about 10(5)  times. Calculations including small-curvature tunneling
      show that the barrier for intermolecular 1,2-hydrogen-transfer reaction is small,
      and QMT leads to a reduced rate of the forward reaction because of nonclassical
      reflections even at room temperature. A small barrier also leads to smaller
      kinetic isotope effects because of efficient QMT by both H and D. QMT does not
      always lead to faster reactions or larger KIE values, particularly when the
      barrier is small. 

PMID- 25044957
TI  - Joint modeling tumor burden and time to event data in oncology trials.
AB  - The tumor burden (TB) process is postulated to be the primary mechanism through
      which most anticancer treatments provide benefit. In phase II oncology trials,
      the biologic effects of a therapeutic agent are often analyzed using conventional
      endpoints for best response, such as objective response rate and progression-free
      survival, both of which causes loss of information. On the other hand, graphical
      methods including spider plot and waterfall plot lack any statistical inference
      when there is more than one treatment arm. Therefore, longitudinal analysis of TB
      data is well recognized as a better approach for treatment evaluation. However,
      longitudinal TB process suffers from informative missingness because of
      progression or death. We propose to analyze the treatment effect on tumor growth
      kinetics using a joint modeling framework accounting for the informative missing
      mechanism. Our approach is illustrated by multisetting simulation studies and an
      application to a nonsmall-cell lung cancer data set. The proposed analyses can be
      performed in early-phase clinical trials to better characterize treatment effect
      and thereby inform decision-making.

PMID- 25044958
TI  - Comparison and analysis of objective functions in flux balance analysis.
AB  - Flux balance analysis (FBA) is currently one of the most important and used
      techniques for estimation of metabolic reaction rates (fluxes). This mathematical
      approach utilizes an optimization criterion in order to select a distribution of
      fluxes from the feasible space delimited by the metabolic reactions and some
      restrictions imposed over them, assuming that cellular metabolism is in steady
      state. Therefore, the obtained flux distribution depends on the specific
      objective function used. Multiple studies have been aimed to compare distinct
      objective functions at given conditions, in order to determine which of those
      functions produces values of fluxes closer to real data when used as objective in
      the FBA; in other words, what is the best objective function for modeling cell
      metabolism at a determined environmental condition. However, these comparative
      studies have been designed in very dissimilar ways, and in general, several
      factors that can change the ideal objective function in a cellular condition have
      not been adequately considered. Additionally, most of them have used only one
      dataset for representing one condition of cell growth, and different measuring
      techniques have been used. For these reasons, a rigorous study on the effect of
      factors such as the quantity of used data, the number and type of fluxes utilized
      as input data, and the selected classification of growth conditions, are required
      in order to obtain useful conclusions for these comparative studies, allowing
      limiting clearly the application range on any of those results.

PMID- 25044959
TI  - Asian common toads in Madagascar: an urgent effort to inform surveys and
      eradication efforts.

PMID- 25044960
TI  - Impairment of homeostasis in lysosomal storage disorders.
AB  - Lysosomal storage disorders (LSDs) are inherited metabolic diseases caused by
      deficiencies in lysosomal proteins, which result in accumulation of undegraded
      metabolites and disruption of lysosomal proteostasis. Despite significant
      progress in the molecular genetics and biochemistry underlying the cellular
      pathogenesis of LSDs, the mechanisms that link accumulation of storage material
      to development and progression of these diseases are still unclear. At the
      crossroad of degradative pathways, lysosomes play a fundamental role in the
      maintenance of cellular homeostasis. Through a series of examples, this review
      illustrates how defects in lysosomal biogenesis and function impact a number of
      cellular pathways that are involved in the pathogenic cascade.

PMID- 25044961
TI  - Epidemiology and survivorship of soft tissue sarcomas in adults: a national
      cancer database report.
AB  - The National Cancer Data Base (NCDB) of the American College of Surgeons gather
      demographic and survival data on ~70% of cancers in the USA. We wanted to
      investigate the demographic and survivorship data on this potentially more
      representative cohort of patients with soft tissue sarcomas. We selected 34 of
      the most commonly encountered soft tissue sarcomas reported to the NCDB, provided
      that each entity contained a minimum of 50 cases. This report summarizes the
      demographic and survivorship data on 63,714 patients with these 34 histologically
      distinct soft tissue sarcomas reported to the NCDB from 1998 to 2010. The overall
      survivorships of these sarcomas were near the lower limits of many prior reports
      due to the all-inclusive, minimally biased inclusion criteria. The overall best
      prognosis was Dermatofibrosarcoma NOS (not otherwise specified). (5-year
      survivorship 92%). The worst prognosis was Dedifferentiated Chondrosarcoma (5
      year survivorship 19%). New observations included Biphasic Synovial Sarcoma
      demonstrating a better 5-year survivorship (65%) compared to spindle-cell
      synovial sarcoma (56%, P < 0.031) and Synovial Sarcoma, NOS (52%, P < 0.001). The
      demographic and 2- and 5-year survivorship data for all 34 soft tissue sarcomas
      are presented herein. This extent of demographic and survival data in soft tissue
      sarcomas is unprecedented. Because of the large number of cases and the inclusive
      nature of the NCDB, without restriction to certain stages, categories, or
      treatments, it is less subject to selection bias. Therefore, these data are
      thought to be more reflective of the true overall prognosis given the current
      management of sarcoma across the NCDB contributing sites. 

PMID- 25044962
TI  - Cobalt-phosphate-assisted photoelectrochemical water oxidation by arrays of
      molybdenum-doped zinc oxide nanorods.
AB  - We report the first demonstration of cobalt phosphate (Co-Pi)-assisted molybdenum
      doped zinc oxide nanorods (Zn(1-x)Mo(x)O NRs) as visible-light-sensitive
      photofunctional electrodes to fundamentally improve the performance of ZnO NRs
      for photoelectrochemical (PEC) water splitting. A maximum photoconversion
      efficiency as high as 1.05% was achieved, at a photocurrent density of 1.4 mA cm(
      2). More importantly, in addition to achieve the maximum incident photon to
      current conversion efficiency (IPCE) value of 86%, it could be noted that the
      IPCE of Zn(1-x)Mo(x)O photoanodes under monochromatic illumination (450 nm) is up
      to 12%. Our PEC performances are comparable to those of many oxide-based
      photoanodes in recent reports. The improvement in photoactivity of PEC water
      splitting may be attributed to the enhanced visible-light absorption, increased
      charge-carrier densities, and improved interfacial charge-transfer kinetics due
      to the combined effect of molybdenum incorporation and Co-Pi modification,
      contributing to photocatalysis. The new design of constructing highly photoactive
      Co-Pi-assisted Zn(1-x)Mo(x)O photoanodes enriches knowledge on doping and
      advances the development of high-efficiency photoelectrodes in the solar-hydrogen
      field.

PMID- 25044963
TI  - A new look at drugs targeting malignant melanoma--an application for mass
      spectrometry imaging.
AB  - Malignant melanoma (MM) patients are being treated with an increasing number of
      personalized medicine (PM) drugs, several of which are small molecule drugs
      developed to treat patients with specific disease genotypes and phenotypes. In
      particular, the clinical application of protein kinase inhibitors has been highly
      effective for certain subsets of MM patients. Vemurafenib, a protein kinase
      inhibitor targeting BRAF-mutated protein, has shown significant efficacy in
      slowing disease progression. In this paper, we provide an overview of this new
      generation of targeted drugs, and demonstrate the first data on localization of
      PM drugs within tumor compartments. In this study, we have introduced MALDI-MS
      imaging to provide new information on one of the drugs currently used in the PM
      treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MS
      imaging was used to identify vemurafenib applied to metastatic lymph nodes tumors
      of subjects attending the regional hospital network of Southern Sweden. The paper
      provides evidence of BRAF overexpression in tumors isolated from MM patients and
      localization of the specific drug targeting BRAF, vemurafenib, using MS fragment
      ion signatures. Our ability to determine drug uptake at the target sites of
      directed therapy provides important opportunity for increasing our understanding
      about the mode of action of drug activity within the disease environment. 

PMID- 25044964
TI  - Aliphatic amine discrimination by pentafluorophenyl dibromo BODIPY.
AB  - Two new fluorescent BODIPY dyes have been designed and synthesized. They dyes
      differ in their meso substituents, which have different electronic properties.
      Their selective reactivity towards an Ar-S(N)2 reaction has been explored as a
      potential basis for colorimetric and fluorescent discrimination of primary,
      secondary and tertiary aliphatic amines. This dual-mode, instantaneous
      recognition event is unprecedented.

PMID- 25044965
TI  - A computational model of drug delivery through microcirculation to compare
      different tumor treatments.
AB  - Starting from the fundamental laws of filtration and transport in biological
      tissues, we develop a computational model to capture the interplay between blood
      perfusion, fluid exchange with the interstitial volume, mass transport in the
      capillary bed, through the capillary walls and into the surrounding tissue. These
      phenomena are accounted at the microscale level, where capillaries and
      interstitial volume are viewed as two separate regions. The capillaries are
      described as a network of vessels carrying blood flow. We apply the model to
      study drug delivery to tumors. The model can be adapted to compare various
      treatment options. In particular, we consider delivery using drug bolus injection
      and nanoparticle injection into the blood stream. The computational approach is
      suitable for a systematic quantification of the treatment performance, enabling
      the analysis of interstitial drug concentration levels, metabolization rates and
      cell surviving fractions. Our study suggests that for the treatment based on
      bolus injection, the drug dose is not optimally delivered to the tumor
      interstitial volume. Using nanoparticles as intermediate drug carriers overrides
      the shortcomings of the previous delivery approach. This work shows that the
      proposed theoretical and computational framework represents a promising tool to
      compare the efficacy of different cancer treatments.

PMID- 25044966
TI  - Highly crystalline lithium titanium oxide sheets coated with nitrogen-doped
      carbon enable high-rate lithium-ion batteries.
AB  - Sheets of Li4Ti5O12 with high crystallinity are coated with nitrogen-doped carbon
      (NC-LTO) using a controlled process, comprising hydrothermal reaction followed by
      chemical vapor deposition (CVD). Acetonitrile (CH3 CN) vapor is used as carbon
      and nitrogen source to obtain a thin coating layer of nitrogen-doped carbon. The
      layer enables the NC-LTO material to maintain its sheet structure during the high
      temperature CVD process and to achieve high crystallinity. Doping with nitrogen
      introduces defects into the carbon coating layer, and this increased degree of
      disorder allows fast transportation of lithium ions in the layer. An electrode of
      NC-LTO synthesized at 700  degrees C exhibits greatly improved rate and cycling
      performance due to a markedly decreased total cell resistance and enhanced Li-ion
      diffusion coefficient (D(Li)). Specific capacities of 159.2 and 145.8 mA h g(-1)
      are obtained using the NC-LTO sheets, at charge/discharge rates of 1 and 10 C,
      respectively. These values are much higher than values for LTO particles did not
      undergo the acetonitrile CVD treatment. A capacity retention value as high as
      94.7% is achieved for the NC-LTO sheets after 400 cycles in a half-cell at 5 C
      discharge rate.

PMID- 25044967
TI  - Total synthesis of gracilamine.
AB  - The total synthesis of gracilamine, a pentacyclic Amaryllidaceae alkaloid, was
      achieved from simple building blocks. The synthesis features a mild photo-Nazarov
      reaction, intramolecular 1,4-addition, and an intramolecular Mannich reaction.
      This approach not only confirms the C6 stereochemistry of natural gracilamine,
      and also provides a novel solution to prepare its derivatives and structurally
      related natural products. 

PMID- 25044968
TI  - A tailor-made chimeric thiamine diphosphate dependent enzyme for the direct
      asymmetric synthesis of (S)-benzoins.
AB  - Thiamine diphosphate dependent enzymes are well known for catalyzing the
      asymmetric synthesis of chiral alpha-hydroxy ketones from simple prochiral
      substrates. The steric and chemical properties of the enzyme active site define
      the product spectrum. Enzymes catalyzing the carboligation of aromatic aldehydes
      to (S)-benzoins have not so far been identified. We were able to close this gap
      by constructing a chimeric enzyme, which catalyzes the synthesis of various (S)
      benzoins with excellent enantiomeric excess (>99%) and very good conversion.

PMID- 25044969
TI  - Anatomically heterogeneous populations of CB1 cannabinoid receptor-expressing
      interneurons in the CA3 region of the hippocampus show homogeneous input-output
      characteristics.
AB  - A subpopulation of GABAergic cells in cortical structures expresses CB1
      cannabinoid receptors (CB1 ) on their axon terminals. To understand the function
      of these interneurons in information processing, it is necessary to uncover how
      they are embedded into neuronal circuits. Therefore, the proportion of GABAergic
      terminals expressing CB1 and the morphological and electrophysiological
      properties of CB1 -immunoreactive interneurons should be revealed. We
      investigated the ratio and the origin of CB1 -expressing inhibitory boutons in
      the CA3 region of the hippocampus. Using immunocytochemical techniques, we
      estimated that ~40% of GABAergic axon terminals in different layers of CA3 also
      expressed CB1 . To identify the inhibitory cell types expressing CB1 in this
      region, we recorded and intracellularly labeled interneurons in hippocampal
      slices. CB1 -expressing interneurons showed distinct axonal arborization, and
      were classified as basket cells, mossy-fiber-associated cells, dendritic-layer
      innervating cells or perforant-path-associated cells. In each morphological
      category, a substantial variability in axonal projection was observed. In
      contrast to the diverse morphology, the active and passive membrane properties
      were found to be rather similar. Using paired recordings, we found that pyramidal
      cells displayed large and fast unitary postsynaptic currents in response to
      activating basket and mossy-fiber-associated cells, while they showed slower and
      smaller synaptic events in pairs originating from interneurons that innervate the
      dendritic layer, which may be due to dendritic filtering. In addition, CB1
      activation significantly reduced the amplitude of the postsynaptic currents in
      each cell pair tested. Our data suggest that CB1 -expressing interneurons with
      different axonal projections have comparable physiological characteristics,
      contributing to a similar proportion of GABAergic inputs along the somato
      dendritic axis of CA3 pyramidal cells.

PMID- 25044970
TI  - Threatened with death but growing: changes in and determinants of posttraumatic
      growth over the dying process for Taiwanese terminally ill cancer patients.
AB  - OBJECTIVE: Posttraumatic growth at end of life, a positive psychological
      consequence of dealing with a life crisis, may be catalyzed by the trauma of
      facing mortality. Studies on cancer patients' posttraumatic growth have
      overwhelmingly examined early-stage survivors. Of the few studies on advanced
      cancer patients, none anchored posttraumatic growth with the patient's death.
      Therefore, the purposes of this study were to describe longitudinal changes in
      and to identify determinants of posttraumatic growth over the dying process.
      METHODS: A convenience sample of 313 cancer patients was recruited and followed
      until death. Posttraumatic growth was measured by the Posttraumatic Growth
      Inventory. Determinants were evaluated from sociodemographics, cancer
      characteristics, social context variables, and coping strategies using a multiple
      linear regression model. RESULTS: The dying process may be too threatening and
      stressful for cancer patients to experience profound posttraumatic growth as
      manifested by low Posttraumatic Growth Inventory scores (26.13 +/- 21.59 to 40.33
      +/- 27.71 on a 0-105 scale) without significant changes as death approached.
      However, terminally ill cancer patients who were not defeated by the initial
      threat of death experienced posttraumatic growth. Patients were at risk for low
      level posttraumatic growth if they were male, were non-middle aged, had low
      educational attainment, had a non-metastatic disease, recently recognized
      terminally ill status, had severe symptom distress, had high functional
      dependence and weak social support, and were unaware or had low acceptance of
      their prognosis. CONCLUSION: Interventions are needed to appropriately relieve
      symptom distress, facilitate functional independence, enhance social support, and
      improve prognostic awareness and acceptance to inspire positive changes for
      cancer patients at end of life.

PMID- 25044971
TI  - Diagnostic cytology in veterinary medicine.

PMID- 25044972
TI  - Luminescence properties of red-emission Mg4 Nb2 O9:Eu3+ phosphor.
AB  - Red-emitting Mg4 Nb2 O9 :Eu(3+) phosphor is synthesized via a solid-state
      reaction method in air, and its crystal structure and luminescence are
      investigated. The phosphor can be excited efficiently by ~ 395 nm light, coupled
      well with a ~ 395 nm near-ultraviolet chip and emits red light at ~ 613 nm with
      sharp spectra due to (5) D0  -> (7)  F2 transition of the Eu(3+) ion. Mg4 Nb2 O9
      :Eu(3+) phosphor sintered at 1350 oC shows Commission international de
      I'Eclairage (CIE) chromaticity coordinates of x = 0.6354, y = 0.3592, and is a
      potential red-emitting phosphor candidate for white light-emitting diodes (W
      LEDs) under ~ 395 nm near-ultraviolet LED chip excitation.

PMID- 25044973
TI  - Photoresponsive switches at surfaces based on supramolecular functionalization
      with azobenzene-oligoglycerol conjugates.
AB  - The synthesis, supramolecular complexation, and switching of new bifunctional
      azobenzene-oligoglycerol conjugates in different environments is reported.
      Through the formation of host-guest complexes with surface immobilized beta
      cyclodextrin receptors, the bifunctional switches were coupled to gold surfaces.
      The isomerization of the amphiphilic azobenzene derivatives was examined in
      solution, on gold nanoparticles, and on planar gold surfaces. The wettability of
      functionalized gold surfaces can be reversibly switched under light-illumination
      with two different wavelengths. Besides the photoisomerization processes and
      concomitant effects on functionality, the thermal cis to trans isomerization of
      the conjugates and their complexes was monitored. Thermal half-lives of the cis
      isomers were calculated for different environments. Surprisingly, the half-lives
      on gold nanoparticles were significantly smaller compared to planar gold
      surfaces. 

PMID- 25044974
TI  - The role of cytopathology and cyst fluid analysis in the preoperative diagnosis
      and management of pancreatic cysts >3 cm.
AB  - BACKGROUND: Pancreatic cyst size >3 cm is a worrisome rather than high-risk
      feature for malignancy based on the 2012 International Guidelines for the
      management of mucinous cysts. The value of cytology in preoperative evaluation
      and surgical triage is unclear. METHODS: All pancreatic cysts >3 cm resected over
      a 7-year period were evaluated for clinical, radiologic, and pathologic
      information. Performance of cytology for the detection of malignancy and surgical
      triage compared with imaging was assessed. RESULTS: There were 93 histologically
      confirmed cysts, 52 of which were mucinous and 41 of which were nonmucinous. Of
      these, 37% were malignant, including 16 nonmucinous malignancies and 18 mucinous
      cysts (12 with invasive carcinoma, 6 with high-grade dysplasia). Thirty-nine
      cysts (41% malignant, 59% benign) were not subject to endoscopic ultrasound-fine
      needle aspiration (EUS-FNA) prior to resection (average size, 6.0 cm). Fifty-four
      were evaluated by EUS-FNA, with 35 available for review (average size, 5.4 cm).
      Cytology/cyst fluid analysis had the highest specificity (88.9%) compared with
      imaging, whereas magnetic resonance imaging (MRI) showed the highest sensitivity
      (100%). MRI had the highest predictive value for mucinous (100%) versus
      nonmucinous cysts (100%). MRI and EUS were able to predict malignancy from the
      presence of high-risk imaging features in all cases. Some benign cases also
      showed high-risk imaging features on MRI (28.6%), computed tomography (32.3%),
      and EUS (45.8%). Cytology correctly classified 5 of 6 benign cysts with high-risk
      imaging as benign. CONCLUSIONS: Preoperative evaluation of pancreatic cysts >3 cm
      is warranted, as many are nonmucinous cysts and not high-grade. Cytology is more
      specific than imaging for the detection of malignancy in cysts >3 cm.

PMID- 25044975
TI  - sox21a directs lateral line patterning by modulating FGF signaling.
AB  - The development of organs composed by repeated functional units is, in many
      cases, accomplished by the transition of cells from a progenitor to a
      differentiation domain, triggering a reiterated developmental program. Yet, how
      these discrete fields are formed during development is still a largely unresolved
      question. The posterior lateral line (pLL), a sensory organ present in fish and
      amphibians, develops from a primordium that migrates along the flanks of the
      animal periodically depositing neuromasts, the pLL functional units. In zebrafish
      (Danio rerio), the developmental program of the pLL is triggered by the transit
      of progenitor cells from a Wnt to a Fgf signaling domain. It has been proposed
      that these two fields are defined by the antagonistic activity of these two
      signaling pathways, but how they are formed and maintained is still an open
      question in the development of the pLL. In this work, we show that sox21a, an HMG
      -box transcription factor, is expressed within the Fgf domain. We demonstrate
      that, while the Fgf signaling pathway do not control sox21a, knockdown of sox21a
      causes impairment of Fgf signaling, expansion of the Wnt signaling domain and
      disruption of neuromast development. These results suggest that sox21a is a key
      player in the pLL primordium patterning, fine-tuning the border of the Fgf and
      Wnt signaling domains.

PMID- 25044976
TI  - Complex tissue-specific epigenotypes in Russell-Silver Syndrome associated with
      11p15 ICR1 hypomethylation.
AB  - Russell-Silver Syndrome (RSS) is a prenatal and postnatal growth retardation
      syndrome caused mainly by 11p15 ICR1 hypomethylation. Clinical presentation is
      heterogeneous in RSS patients with 11p15 ICR1 hypomethylation. We previously
      identified a subset of RSS patients with 11p15 ICR1 and multilocus
      hypomethylation. Here, we examine the relationships between IGF2 expression,
      11p15 ICR1 methylation, and multilocus imprinting defects in various cell types
      from 39 RSS patients with 11p15 ICR1 hypomethylation in leukocyte DNA. 11p15 ICR1
      hypomethylation was more pronounced in leukocytes than in buccal mucosa cells.
      Skin fibroblast IGF2 expression was correlated with the degree of ICR1
      hypomethylation. Different tissue-specific multilocus methylation defects
      coexisted in 38% of cases, with some loci hypomethylated and others
      hypermethylated within the same cell type in some cases. Our new results suggest
      that tissue-specific epigenotypes may lead to clinical heterogeneity in RSS. 

PMID- 25044977
TI  - BDNF Val66Met genotype interacts with childhood adversity and influences the
      formation of hippocampal subfields.
AB  - Childhood stress and genetic factors like the Val66MET polymorphism of the brain
      derived neurotrophic factor (BDNF) gene are associated with a higher risk for
      developing major depressive disorder (MDD) and might also influence hippocampal
      changes. The aim of this study was to determine which hippocampal dentate gyrus
      and cornu ammonis subfields are altered in MDD compared to healthy controls and
      which subfields are affected by the BDNF Val66Met polymorphism and child
      adversity. Adult patients with MDD and healthy matched controls underwent high
      resolution magnetic resonance imaging. Automatic segmentation using the programme
      FreeSurfer was used to segment the hippocampal subfields dentate gyrus (DG/CA4),
      CA1 and CA2/3. The history of possible childhood adversity was assessed using the
      Childhood Trauma Questionnaire and the Val66Met BDNF SNP (rs6265) genotypes were
      obtained. Patients with MDD had significantly smaller CA4/DG and CA2/3 volumes
      compared to healthy controls. Furthermore, there was a significant interactive
      effect of BDNF allele and childhood adversity on CA2/3 and CA4/DG volumes. Met
      allele carriers without childhood adversity had larger and with childhood
      adversity smaller CA4/DG and CA2/3 volumes than Val-allele homozygotes. Our
      results highlight stress by gene interactions as relevant for hippocampal volume
      reductions, in particular for the subfield CA2/3 and dentate gyrus.

PMID- 25044978
TI  - Dynamic contrast-enhanced MRI of gastric cancer: Correlation of the perfusion
      parameters with pathological prognostic factors.
AB  - PURPOSE: To investigate the feasibility of dynamic, contrast-enhanced, magnetic
      resonance imaging (DCE-MRI) for perfusion quantification of gastric cancers, and
      to correlate the DCE-MRI parameters with the pathological prognostic factors.
      MATERIALS AND METHODS: This prospective study was approved by our Institutional
      Review Board. Twenty-seven patients with gastric cancers underwent DCE-MRI using
      a free-breathing, radial, gradient-echo (GRE) sequence with k-space weighted
      image contrast (KWIC) reconstruction on a 3T scanner. The DCE-MRI parameters
      (volume transfer coefficient [K(trans) ], reverse reflux rate constant [Kep ],
      extracellular extravascular volume fraction [Ve ], and initial area under the
      gadolinium concentration curve during the first 60 seconds [iAUC]) of gastric
      cancer and normal wall were measured and compared with each other using the
      Wilcoxon signed rank test. The relationship between the DCE-MRI parameters of
      gastric cancer and the pathological prognostic factors were evaluated using the
      Mann-Whitney test or the Spearman rank correlation test. RESULTS: DCE-MRIs were
      of diagnostic quality in 22 patients (81.5%). Ve and iAUC were significantly
      higher in gastric cancer than in normal gastric wall (P < 0.05). Ve showed
      significant positive correlation with T-staging of gastric cancers (P < 0.05).
      K(trans) was significantly correlated with the grades of epidermal growth-factor
      receptor expression (P < 0.05). CONCLUSION: DCE-MRI using a radial GRE with KWIC
      reconstruction is feasible for quantification of the perfusion dynamics of
      gastric cancers, and the DCE-MRI parameters of gastric cancers may provide
      prognostic information.

PMID- 25044979
TI  - Telomere distribution pattern and synapsis initiation during spermatogenesis in
      zebrafish.
AB  - BACKGROUND: Telomeres are located at ends of eukaryotic chromosomes and can
      affect proper chromosomal positioning. During spermatogenesis, the appropriate
      dynamics and behavior of chromosomes is crucial to generate haploid cells through
      meiosis. Here, we describe telomere distribution patterns during spermatogenesis
      in zebrafish, especially during meiotic prophase I, using fluorescence in situ
      hybridization. This was combined with synaptonemal complex protein 3
      immunostaining, which allows the staging of spermatocytes. RESULTS: During
      spermatogonial proliferation and the preleptotene stage, telomeres were dispersed
      throughout the nucleus. During the leptotene stage, telomeres temporarily moved
      to one pole of the nucleus at which gamma-tubulin was located, forming the
      telomere bouquet. The cluster lasted until the onset of zygotene where it
      coincided with terminal synapsis initiation. They then spread around the
      periphery of the nucleus during the zygotene to pachytene stages. During
      postmeiotic stages, telomeres in spermatids and sperm were again dispersed
      throughout the nuclei. Application of this procedure in meiotic mutants confirmed
      that meiotic telomere clustering is independent of axial element formation of the
      synaptonemal complex. CONCLUSIONS: These data clearly showed the clustering and
      distributions of telomeres throughout spermatogenesis in zebrafish. This
      procedure could be used to screen for mutants that have primary defects in
      telomere clustering.

PMID- 25044980
TI  - Bcl-2 down-regulation by small interfering RNA induces Beclin1-dependent
      autophagy in human SGC-7901 cells.
AB  - While Bcl-2 protein is involved in the regulation of apoptosis, recent research
      showed that Beclin1, described as the essential autophagy effector and
      haploinsufficient tumor suppressor, was originally isolated as a Bcl-2
      interacting protein. Beclin1 interacts with Bcl-2 through a BH3 domain;
      nevertheless, the function of the anti-apoptotic gene, Bcl-2, in autophagy is not
      well understood. We explored the role of Bcl-2 in autophagy in human SGC-7901
      cells in which Bcl-2 is overexpressed. Knockdown of Bcl-2 by small interfering
      RNA in human SGC-7901 cells downregulated Bcl-2 protein levels ~82% and induced
      autophagy. Beclin1 protein, the first identified autophagy gene product, was
      induced by as much as 58%. Transmission electron microscopy and DNA fragmentation
      assay showed that autophagy was enhanced, but not apoptosis, in Bcl-2 siRNA
      treated cells. The results provide evidence that knockout the anti-apoptotic gene
      Bcl-2 induces autophagy in SGC-7901 cells and Bcl-2 specific siRNA may be used as
      a potential therapeutic strategy in gastric cancer cells that overexpress Bcl-2. 

PMID- 25044981
TI  - Design of a general-purpose European compound screening library for EU
      OPENSCREEN.
AB  - This work describes a collaborative effort to define and apply a protocol for the
      rational selection of a general-purpose screening library, to be used by the
      screening platforms affiliated with the EU-OPENSCREEN initiative. It is designed
      as a standard source of compounds for primary screening against novel biological
      targets, at the request of research partners. Given the general nature of the
      potential applications of this compound collection, the focus of the selection
      strategy lies on ensuring chemical stability, absence of reactive compounds,
      screening-compliant physicochemical properties, loose compliance to drug-likeness
      criteria (as drug design is a major, but not exclusive application), and maximal
      diversity/coverage of chemical space, aimed at providing hits for a wide spectrum
      of drugable targets. Finally, practical availability/cost issues cannot be
      avoided. The main goal of this publication is to inform potential future users of
      this library about its conception, sources, and characteristics. The outline of
      the selection procedure, notably of the filtering rules designed by a large
      committee of European medicinal chemists and chemoinformaticians, may be of
      general methodological interest for the screening/medicinal chemistry community.
      The selection task of 200K molecules out of a pre-filtered set of 1.4M candidates
      was shared by five independent European research groups, each picking a subset of
      40K compounds according to their own in-house methodology and expertise. An in
      depth analysis of chemical space coverage of the library serves not only to
      characterize the collection, but also to compare the various chemoinformatics
      driven selection procedures of maximal diversity sets. Compound selections
      contributed by various participating groups were mapped onto general-purpose self
      organizing maps (SOMs) built on the basis of marketed drugs and bioactive
      reference molecules. In this way, the occupancy of chemical space by the EU
      OPENSCREEN library could be directly compared with distributions of known
      bioactives of various classes. This mapping highlights the relevance of the
      selection and shows how the consensus reached by merging the five different 40K
      selections contributes to achieve this relevance. The approach also allows one to
      readily identify subsets of target- or target-class-oriented compounds from the
      EU-OPENSCREEN library to suit the needs of the diverse range of potential users.
      The final EU-OPENSCREEN library, assembled by merging five independent selections
      of 40K compounds from various expert groups, represents an excellent example of a
      Europe-wide collaborative effort toward the common objective of building best-in
      class European open screening platforms. 

PMID- 25044982
TI  - Baking, ageing, diabetes: a short history of the Maillard reaction.
AB  - The reaction of reducing carbohydrates with amino compounds described in 1912 by
      Louis-Camille Maillard is responsible for the aroma, taste, and appearance of
      thermally processed food. The discovery that non-enzymatic conversions also occur
      in organisms led to intensive investigation of the pathophysiological
      significance of the Maillard reaction in diabetes and ageing processes. Dietary
      Maillard products are discussed as "glycotoxins" and thus as a nutritional risk,
      but also increasingly with regard to positive effects in the human body. In this
      Review we give an overview of the most important discoveries in Maillard research
      since it was first described and show that the complex reaction, even after over
      one hundred years, has lost none of its interdisciplinary actuality. 

PMID- 25044983
TI  - The scale-up of a tissue engineered porous hydroxyapatite polymer composite
      scaffold for use in bone repair: an ovine femoral condyle defect study.
AB  - The development of an osteogenic bone graft substitute has important practical
      and cost implications in many branches of medicine where bone regeneration is
      required. Previous in vitro and small animal (murine) in vivo studies highlighted
      a porous hydroxyapatite/poly (DL-lactic acid) composite scaffold in combination
      with skeletal stem cells (SSCs) as a potential bone graft substitute candidate.
      The aim of the current study was to scale up the bone cell-scaffold construct to
      large animals and examine the potential for repair of a critical-sized defect via
      an ovine model. SSC seeded scaffolds (and unseeded scaffold controls) were
      implanted bilaterally into ovine femoral condyle critical defects for 3 months. A
      parallel in vitro analysis of ovine SSC seeded scaffolds was also performed. Post
      mortem mechanical indentation testing showed the bone strengths of the defect
      sites were 20% (controls) and 11% (SSC seeded scaffolds) those of normal
      cancellous bone (p < 0.01). MicroCT analysis demonstrated new bone formation
      within all defects with a mean increase of 13.4% in the control scaffolds over
      the SSC seeded scaffolds (p = 0.14). Histological examination confirmed these
      findings, with enhanced quality new bone within the control defects. This study
      highlights important issues and steps to overcome in scale-up and translation of
      tissue engineered products. The scaffold demonstrated encouraging results as an
      osteoconductive matrix; however, further work is required with cellular protocols
      before any human trials.

PMID- 25044984
TI  - A comparison of cell mediators and serum cytokines transcript expression between
      male and female mice infected with Mycobacterium avium subspecies
      paratuberculosis and/or consuming probiotics.
AB  - The gut immune system is complex, and dysregulation leads to a number of
      disorders including inflammatory bowel syndrome and (in livestock) Johne's
      disease. Previous work has demonstrated that males and females respond
      differently to treatment with pathologic and probiotic microorganisms, suggesting
      that a 'one-size-fits-all' approach to treat GIT inflammation may be inadequate.
      While we had observed significant differences between males and females in terms
      of cytokine production, it remains unclear how these changes occur. To better
      understand the mechanisms, transcript expression of genes important to gut
      immunoregulation were monitored from male and female BALB/c mice consuming the
      probiotic Lactobacillus animalis (1 * 10(6) CFU g(-1) ) and infected with the gut
      pathogen, Mycobacterium avium subspecies paratuberculosis (1 * 10(7) CFU).
      Expression of transcripts analyzed included those important to the immune system,
      intestinal cell differentiation, and/or regulation. Males generally displayed
      increased expression of Th 2 and B-cell mediators, and females showed repressed
      cytokine expression after MAP infection (IL-6, TNF-alpha, IL-1 among others).
      Additionally, regulation of pro-inflammatory mediators in female mice consuming
      probiotics suggests females responded positively to L. animalis when compared to
      males. Therefore, we speculate that studying mechanistic changes associated with
      sex and immunoregulation in gastrointestinal tissues could further elucidate host
      response to microorganisms.

PMID- 25044985
TI  - Evaluation of perovskites as electrocatalysts for the oxygen evolution reaction.
AB  - The oxygen evolution reaction (OER) is an enabling process for technologies in
      the area of energy conversion and storage, but its slow kinetics limits its
      efficiency. We performed an electrochemical evaluation of 14 different
      perovskites of variable composition and stoichiometry as OER electrocatalysts in
      alkaline media. We particularly focused on improved methods for a reliable
      comparison of catalyst activity. From initial electrochemical results we selected
      the most active samples for further optimization of electrode preparation and
      testing. An inverted cell configuration facilitated gas bubble detachment and
      thus minimized blockage of the active surface area. We describe parameters, such
      as the presence of specific cations, stoichiometry, and conductivity, that are
      important for obtaining electroactive perovskites for OER. Conductive additives
      enhanced the current and decreased the apparent overpotential of OER for one of
      the most active samples (La(0.58)Sr(0.4)Fe(0.8)Co(0.2)O(3)).

PMID- 25044986
TI  - Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA
      mutation in cultured amniocytes.
AB  - Congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary,
      venous, and combined-type vascular malformations, epidermal nevi, skeletal and
      spinal anomalies (CLOVES) syndrome, a segmental overgrowth syndrome, is caused by
      post zygotic somatic mutations in PIK3CA, a gene involved in the receptor
      tyrosine kinase phosphatidylinositol 3-kinase (PI3)-AKT growth-signaling pathway.
      Prenatal ultrasound findings of lymphovascular malformations, segmental
      overgrowth and skeletal defects can raise suspicion for CLOVES syndrome, but
      molecular confirmation of PIK3CA mutations on prenatally obtained samples is
      challenging because of somatic mosaicism. We detected a mosaic disease-causing
      mutation in PIK3CA by sequencing of DNA extracted from cultured amniotic cells,
      but not from DNA directly prepared from an amniotic fluid sample in a fetus with
      prenatally suspected CLOVES syndrome. The infant was born prematurely and
      displayed severe lymphovascular malformations and segmental overgrowth consistent
      with a clinical diagnosis of CLOVES syndrome; he passed away at 29 days of life.
      We discuss the complexities and limitations of genetic testing for somatic mosaic
      mutations in the prenatal period and highlight the potential need for multiple
      approaches to arrive at a molecular diagnosis. (c) 2014 Wiley Periodicals, Inc. 

PMID- 25044987
TI  - Trauma in relation to psychosis and hospital experiences: the role of past trauma
      and attachment.
AB  - OBJECTIVES: We investigated rates of psychosis-related and hospital-related post
      traumatic stress disorder (PTSD) in people with psychosis in secure settings. We
      also investigated relationships between PTSD symptoms and previous experiences of
      trauma and adult attachment. METHOD: Using a cross-sectional design, 50
      participants from medium-secure and low-secure settings were interviewed to
      identify distressing experiences related to psychosis and hospitalization. PTSD
      symptoms related to those experiences, past trauma and attachment were assessed
      using self-report measures. RESULTS: The combined rate of psychosis-related and
      hospital-related PTSD was 30%. Twenty-four percent and 18% met criteria for
      psychosis-related and hospital-related PTSD, respectively. Severity of psychosis
      was associated with both psychosis-related and hospital-related PTSD symptoms.
      The prevalence of previous trauma was high, but previous trauma was not
      significantly correlated with psychosis-related or hospital-related PTSD
      symptoms. Anxiety in attachment relationships was significantly associated with
      both psychosis-related PTSD symptoms and hospital-related PTSD symptoms.
      CONCLUSIONS: This study adds to the growing body of research highlighting the
      distressing nature of psychosis and the iatrogenic effects of treatments. It also
      highlights the potentially important role of attachment styles in PTSD in
      psychosis. PRACTITIONER POINTS: 30% of patients met criteria for psychosis- or
      hospital-related PTSD. Severity of psychosis was associated with PTSD symptoms.
      Anxiety in attachment relationships was positively correlated with PTSD symptoms.

PMID- 25044988
TI  - Effect of dietary fat modification on subcutaneous white adipose tissue insulin
      sensitivity in patients with metabolic syndrome.
AB  - SCOPE: To determine whether the insulin resistance that exists in metabolic
      syndrome (MetS) patients is modulated by dietary fat composition. METHODS AND
      RESULTS: Seventy-five patients were randomly assigned to one of four diets for 12
      wk: high-saturated fatty acids (HSFAs), high-MUFA (HMUFA), and two low-fat, high
      complex carbohydrate (LFHCC) diets supplemented with long-chain n-3 (LFHCC n-3)
      PUFA or placebo. At the end of intervention, the LFHCC n-3 diet reduced plasma
      insulin, homeostasis model assessment of insulin resistance, and nonsterified
      fatty acid concentration (p < 0.05) as compared to baseline Spanish habitual
      (BSH) diet. Subcutaneous white adipose tissue (WAT) analysis revealed decreased
      EH-domain containing-2 mRNA levels and increased cbl-associated protein gene
      expression with the LFHCC n-3 compared to HSFA and HMUFA diets, respectively (p <
      0.05). Moreover, the LFHCC n-3 decreased gene expression of glyceraldehyde-3
      phosphate dehydrogenase with respect to HMUFA and BSH diets (p < 0.05). Finally,
      proteomic characterization of subcutaneous WAT identified three proteins of
      glucose metabolism downregulated by the LFHCC n-3 diet, including annexin A2. RT
      PCR analysis confirmed the decrease of annexin A2 (p = 0.027) after this diet.
      CONCLUSION: Our data suggest that the LFHCC n-3 diet reduces systemic insulin
      resistance and improves insulin signaling in subcutaneous WAT of MetS patients
      compared to HSFA and BSH diets consumption.

PMID- 25044990
TI  - Selective capture of carbon dioxide under humid conditions by hydrophobic
      chabazite-type zeolitic imidazolate frameworks.
AB  - Hydrophobic zeolitic imidazolate frameworks (ZIFs) with the chabazite (CHA)
      topology are synthesized by incorporating two distinct imidazolate links. Zn(2
      mIm)0.86 (bbIm)1.14 (ZIF-300), Zn(2-mIm)0.94 (cbIm)1.06 (ZIF-301), and Zn(2
      mIm)0.67 (mbIm)1.33 (ZIF-302), where 2-mIm = 2-methylimidazolate, bbIm = 5(6)
      bromobenzimidazolate, cbIm = 5(6)-chlorobenzimidazolate, and mbIm = 5(6)
      methylbenzimidazolate, were prepared by reacting zinc nitrate tetrahydrate and 2
      mIm with the respective bIm link in a mixture of N,N-dimethylformamide (DMF) and
      water. Their structures were determined by single-crystal X-ray diffraction and
      their permanent porosity shown. All of these structures are hydrophobic as
      confirmed by water adsorption isotherms. All three ZIFs are equally effective at
      the dynamic separation of CO2 from N2 under both dry and humid conditions without
      any loss of performance over three cycles and can be regenerated simply by using
      a N2 flow at ambient temperature.

PMID- 25044989
TI  - Association of sports drinks with weight gain among adolescents and young adults.
AB  - OBJECTIVE: Sales of regular soda were declining, but sales of other sweetened
      beverages, such as sports drinks, were increasing. Our objective was to determine
      the prospective associations between sports drinks and body mass index (BMI)
      gains among adolescents and young adults. METHODS: 4121 females and 3438 males in
      the Growing Up Today Study II, aged 9-16 in 2004, from across the United States
      were followed prospectively. Data were collected by questionnaire in 2004, 2006,
      2008, and 2011. Servings per day of various beverages were assessed with a food
      frequency questionnaire. RESULTS: Among the girls, each serving per day of sports
      drink predicted an increase of 0.3 BMI units (95% confidence interval (CI) CI
      0.03-0.54) more than their peers over the next 2-3 years. Among the males, each
      serving of sports drinks predicted a 0.33 BMI (95% CI 0.09, 0.66) increase. In
      addition, boys who increased their intake over the 2-3 year interval gained
      significantly more than their peers during the same time interval. CONCLUSIONS:
      Intake of sports drinks predicted larger increases in BMI among both females and
      males. Our results suggest that school policies focused on obesity prevention
      should be augmented to restrict sports drinks.

PMID- 25044991
TI  - Multifunctional electroactive heteroatom-doped carbon aerogels.
AB  - The design and synthesis of highly active, durable, and cheap nanomaterials for
      various renewable energy storage and conversion applications is extremely
      desirable but remains challenging. Here, a green and efficient strategy to
      produce CoOx nanoparticles and surface N-co-doped carbon aerogels (Co-N-CAs) is
      reported by multicomponent surface self-assembly of commercially melamine sponge
      (CMS). In the methodology, the CMS simultaneously function as green N precursor
      for surface N doping and 3D support. The resulting Co-N-CAs exhibit 3D
      hierarchical, interconnected macro- and bimodal meso-porosity (6.3 nm and <4 nm),
      high surface area (1383 m(2) g(-1)), and highly dispersed, semi-exposured CoOx
      nanoparticles (diameter of 12.5 nm). The surface doping of N, semi-exposured
      configuration of CoOx nanoparticles and the penetrated complementary pores (<4
      nm) in the carbon walls provide highly accessibility between electroactive
      components and electrolytes to improve reactivity. With their tailored
      architecture, the Co-N-CAs show superior electrocatalytic oxygen reduction (ORR)
      activities comparable to the commercially Pt/C catalysts, high specific
      capacitance (433 F g(-1)), excellent lithium storage (938 mAh g(-1)), and
      outstanding durability, making them very promising for advanced energy conversion
      and storage. In addition, the presented strategy can be extended to fabricate
      other metal oxide- and N-co-doped carbon aerogels for diverse energy-related
      applications.

PMID- 25044992
TI  - Synthesis of densely phosphorylated bis-1,5-diphospho-myo-inositol
      tetrakisphosphate and its enantiomer by bidirectional P-anhydride formation.
AB  - The ubiquitous mammalian signaling molecule bis-diphosphoinositol
      tetrakisphosphate (1,5-(PP)2 -myo-InsP4 , or InsP8 ) displays the most congested
      three-dimensional array of phosphate groups found in nature. The high charge
      density, the accumulation of unstable P-anhydrides and P-esters, the lack of UV
      absorbance, and low levels of optical rotation constitute severe obstacles to its
      synthesis, characterization, and purification. Herein, we describe the first
      procedure for the synthesis of enantiopure 1,5-(PP)2 -myo-InsP4 and 3,5-(PP)2 
      myo-InsP4 utilizing a C2 -symmetric P-amidite for desymmetrization and
      concomitant phosphitylation followed by a one-pot bidirectional P-anhydride
      forming reaction that combines sixteen chemical transformations with high
      efficiency. The configuration of these materials is unambiguously shown by
      subsequent X-ray analyses of both enantiomers after being individually soaked
      into crystals of the kinase domain of human diphosphoinositol pentakisphosphate
      kinase 2. 

PMID- 25044993
TI  - Gleaning unexpected fruits from hard-won synthetases: probing principles of
      permissivity in non-canonical amino acid-tRNA synthetases.
AB  - The site-specific incorporation of non-canonical amino acids (ncAAs) into
      proteins is an important tool for understanding biological function.
      Traditionally, each new ncAA targeted for incorporation requires a resource
      consuming process of generating new ncAA aminoacyl tRNA synthetase/tRNACUA pairs.
      However, the discovery that some tRNA synthetases are "permissive", in that they
      can incorporate multiple ncAAs, means that it is no longer always necessary to
      develop a new synthetase for each newly desired ncAA. Developing a better
      understanding of what factors make ncAA synthetases more permissive would
      increase the utility of this new approach. Here, we characterized two synthetases
      selected for the same ncAA that have markedly different "permissivity profiles."
      Remarkably, the more permissive synthetase incorporated an ncAA for which we had
      not been able to generate a synthetase through de novo selection methods. Crystal
      structures revealed that the two synthetases recognize their parent ncAA through
      a conserved core of interactions, with the more permissive synthetase displaying
      a greater degree of flexibility in its interaction geometries. We also observed
      that intraprotein interactions not directly involved in ncAA binding can play a
      crucial role in synthetase permissivity and suggest that optimization of such
      interactions might provide an avenue to engineering synthetases with enhanced
      permissivity. 

PMID- 25044994
TI  - Construction of a portable sample preparation device with a magnetic
      poly(methacrylic acid-co-ethylene dimethacrylate) monolith as the extraction
      medium and its application in the enrichment of UV filters in water samples.
AB  - A portable sample preparation device with a magnetic polymer monolith as the
      extraction medium was constructed. The monolith was synthesized by polymerizing
      methacrylic acid and ethylene dimethacrylate around a cylindrical magnet. In this
      way, the monolith with a magnetic core could be readily attached to the
      extraction device by magnetism. The constructed device was evaluated for the
      enrichment of UV filters in water samples, followed by high-performance liquid
      chromatographic analysis. The extraction efficiency for the targets was
      satisfactory with no matrix interference. Good linearities were obtained for the
      UV filters with the correlation coefficients >0.9986. The limits of detection and
      quantification for the UV filters were 0.3-0.8 and 1.0-2.4 ng/mL, respectively.
      The recoveries of the UV filters from the spiked water samples at the
      concentration of 100 ng/mL were 95.3-101.7%, with relative standard deviations
      <10%. Accordingly, the proposed portable device was demonstrated to be suitable
      for on-site simultaneous sampling, purification, and preconcentration within a
      single step. 

PMID- 25044995
TI  - Hemoglobin regulates the migration of glioma cells along poly(epsilon
      caprolactone)-aligned nanofibers.
AB  - Aligned fibers have been shown to facilitate cell migration in the direction of
      fiber alignment while oxygen (O2 )-carrying solutions improve the metabolism of
      cells in hypoxic culture. Therefore, U251 aggregate migration on poly(epsilon
      caprolactone) (PCL)-aligned fibers was studied in cell culture media supplemented
      with the O2 storage and transport protein hemoglobin (Hb) obtained from bovine,
      earthworm and human sources at concentrations ranging from 0 to 5 g/L within a
      cell culture incubator exposed to O2 tensions ranging from 1 to 19% O2 .
      Individual cell migration was quantified using a wound healing assay. In
      addition, U251 cell aggregates were developed and aggregate dispersion/cell
      migration quantified on PCL-aligned fibers. The results of this work show that
      the presence of bovine or earthworm Hb improved individual cell viability at 1%
      O2 , while human Hb adversely affected cell viability at increasing Hb
      concentrations and decreasing O2 levels. The control data suggests that
      decreasing the O2 tension in the incubator from 5 to 1% O2 decreased aggregate
      dispersion on the PCL-aligned fibers. However, the addition of bovine Hb at 5% O2
      significantly improved aggregate dispersion. At 19% O2 , Hb did not impact
      aggregate dispersion. Also at 1% O2 , aggregate dispersion appeared to increase
      in the presence of earthworm Hb, but only at the latter time points. Taken
      together, these results show that Hb-based O2 carriers can be utilized to improve
      O2 availability and the migration of glioma spheroids on nanofibers.

PMID- 25044996
TI  - How did the Canterbury earthquakes affect physiotherapists and physiotherapy
      services? A qualitative study.
AB  - BACKGROUND AND PURPOSE: The recent earthquakes in Canterbury New Zealand ended
      lives and resulted in disruption to many aspect of life for survivors, including
      physiotherapists. Physiotherapists often volunteer vital rehabilitation services
      in the wake of global disasters; however, little is known about how
      physiotherapists cope with disasters that affect their own communities. The
      purpose of this study was to investigate how the Canterbury earthquakes affected
      physiotherapists and physiotherapy services. METHODS: We use a General Inductive
      Approach to analyse data obtained from purposively sampled physiotherapists or
      physiotherapy managers in the Canterbury region. Interviews were audio-recorded
      and transcribed verbatim. RESULTS: We analysed data from interviews with 27
      female and six male participants. We identified four themes: 'A life-changing
      earthquake' that described how both immediate and on-going events led to our
      second theme 'Uncertainty'. Uncertainty eroded feelings of resilience, but this
      was tempered by our third theme 'Giving and receiving support'. Throughout these
      three themes, we identified a further theme 'Being a physiotherapist'. This theme
      explains how physiotherapists and physiotherapy services were and still are
      affected by the Canterbury earthquakes. DISCUSSION: We recommend that disaster
      planning occurs at individual, departmental, practice and professional levels.
      This planning will enable physiotherapists to better cope in the event of a
      disaster and would help to provide professional bodies with a cohesive set of
      skills that can be shared with health agencies and rescue organizations. We
      recommend that the apparently vital skill of listening is explored through
      further research in order for it to be better accepted as a core physiotherapy
      skill.

PMID- 25044997
TI  - Assessing the prediction accuracy of cure in the Cox proportional hazards cure
      model: an application to breast cancer data.
AB  - A cure rate model is a survival model incorporating the cure rate with the
      assumption that the population contains both uncured and cured individuals. It is
      a powerful statistical tool for prognostic studies, especially in cancer. The
      cure rate is important for making treatment decisions in clinical practice. The
      proportional hazards (PH) cure model can predict the cure rate for each patient.
      This contains a logistic regression component for the cure rate and a Cox
      regression component to estimate the hazard for uncured patients. A measure for
      quantifying the predictive accuracy of the cure rate estimated by the Cox PH cure
      model is required, as there has been a lack of previous research in this area. We
      used the Cox PH cure model for the breast cancer data; however, the area under
      the receiver operating characteristic curve (AUC) could not be estimated because
      many patients were censored. In this study, we used imputation-based AUCs to
      assess the predictive accuracy of the cure rate from the PH cure model. We
      examined the precision of these AUCs using simulation studies. The results
      demonstrated that the imputation-based AUCs were estimable and their biases were
      negligibly small in many cases, although ordinary AUC could not be estimated.
      Additionally, we introduced the bias-correction method of imputation-based AUCs
      and found that the bias-corrected estimate successfully compensated the
      overestimation in the simulation studies. We also illustrated the estimation of
      the imputation-based AUCs using breast cancer data.

PMID- 25044999
TI  - New prognostic factors and scoring system for patients with skeletal metastasis.
AB  - The aim of this study was to update a previous scoring system for patients with
      skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing
      a new factor (laboratory data) and analyzing a new patient cohort. Between
      January 2005 and January 2008, we treated 808 patients with symptomatic skeletal
      metastases. They were prospectively registered regardless of their treatments,
      and the last follow-up evaluation was performed in 2012. There were 441 male and
      367 female patients with a median age of 64 years. Of these patients, 749 were
      treated nonsurgically while the remaining 59 underwent surgery for skeletal
      metastasis. A multivariate analysis was conducted using the Cox proportional
      hazards model. We identified six significant prognostic factors for survival,
      namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory
      data, poor performance status, previous chemotherapy, and multiple skeletal
      metastases. The first three factors had a larger impact than the remaining three.
      The prognostic score was calculated by adding together all the scores for
      individual factors. With a prognostic score of >=7, the survival rate was 27% at
      6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of
      <=3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the
      revised system with the previous one, there was a significantly lower number of
      wrongly predicted patients using the revised system. This revised scoring system
      was able to predict the survival rates of patients with skeletal metastases more
      accurately than the previous system and may be useful for selecting an optimal
      treatment. 

PMID- 25045000
TI  - Virtual reality therapies for phantom limb pain.

PMID- 25044998
TI  - Penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus.
AB  - High-level resistance to beta-lactam antibiotics in methicillin-resistant
      Staphylococcus aureus (MRSA) is due to expression of penicillin-binding protein
      2a (PBP2a), a transpeptidase that catalyzes cell-wall crosslinking in the face of
      the challenge by beta-lactam antibiotics. The activity of this protein is
      regulated by allostery at a site 60 A distant from the active site, where
      crosslinking of cell wall takes place. This review discusses the state of
      knowledge on this important enzyme of cell-wall biosynthesis in MRSA.

PMID- 25045001
TI  - Exploring the roles of body ownership, vision and virtual reality on heat pain
      threshold.

PMID- 25045002
TI  - Hepatic artery and biliary complications in liver transplant recipients
      undergoing pretransplant transarterial chemoembolization.
AB  - Liver transplantation (LT) is the treatment of choice for patients with cirrhosis
      and hepatocellular carcinoma (HCC) not amenable to resection. Locoregional
      therapies for HCC are often used to reduce tumor burden, bridge patients to LT,
      and down-stage HCC so that patients are eligible for LT. We hypothesized that
      prior endovascular antitumor therapy may increase the risk of hepatic artery (HA)
      and biliary complications after LT. The aim of this study was to compare HA and
      biliary complications in LT recipients with HCC who received transarterial
      chemoembolization (TACE) before LT with complications in LT recipients with HCC
      who did not receive TACE before LT. This was a retrospective cohort study of HCC
      patients at two transplant centers. The prevalence of HA complications (HA
      thrombosis, stenosis, or pseudoaneurysm) and biliary complications
      (nonanastomotic stricture, bile leak, and diffuse injury) were compared between
      patients treated with or without TACE. There were 456 HCC patients with a median
      age of 61 years (77% were male, and 63% had hepatitis C virus), and 328 (72%)
      received TACE before LT. The overall prevalence of HA complications was 4.7% in
      the no-TACE group and 7.9% in the TACE group (P = 0.22). All HA stenosis
      complications (n = 14) occurred in the TACE group (P = 0.018 versus the no-TACE
      group). An older donor age and a lower albumin level significantly increased the
      odds of HA complications. There was a nonstatistically significant increased odds
      of HA complications in the TACE group versus the no-TACE group according to an
      adjusted analysis (odds ratio = 2.02, 95% confidence interval = 0.79-5.16, P =
      0.14). The overall prevalence of biliary complications was 16.4% in the no-TACE
      group and 19.8% in the TACE group (P = 0.40). In conclusion, a lower pre-LT
      albumin level and an older donor age were significantly associated with higher
      odds of HA complications after LT. TACE was not associated with higher odds of
      overall HA complications but was associated with a higher prevalence of HA
      stenosis. Further studies are warranted to confirm the HA stenosis findings and
      elucidate the pathogenesis.

PMID- 25045005
TI  - A tailored catalyst for the sustainable conversion of glycerol to acrolein:
      mechanistic aspect of sequential dehydration.
AB  - Developing a catalyst to resolve deactivation caused from coke is a primary
      challenge in the dehydration of glycerol to acrolein. An open-macropore
      structured and Bronsted-acidic catalyst (Marigold-like silica functionalized with
      sulfonic acid groups, MS-FS) was synthesized for the stable and selective
      production of acrolein from glycerol. A high acrolein yield of 73% was achieved
      and maintained for 50 h in the presence of the MS-FS catalyst. The hierarchical
      structure of the catalyst with macropores was found to have an important effect
      on the stability of the catalyst because coke polymerization and pore blocking
      caused by coke deposition were inhibited. In addition, the behavior of 3
      hydroxypropionaldehyde (3-HPA) during the sequential dehydration was studied
      using density functional theory (DFT) calculations because 3-HPA conversion is
      one of the main causes for coke formation. We found that the easily reproducible
      Bronsted acid sites in MS-FS permit the selective and stable production of
      acrolein. This is because the reactive intermediate (3-HPA) is readily adsorbed
      on the regenerated acid sites, which is essential for the selective production of
      acrolein during the sequential dehydration. The regeneration ability of the acid
      sites is related not only to the selective production of acrolein but also to the
      retardation of catalyst deactivation by suppressing the formation of coke
      precursors originating from 3-HPA degradation.

PMID- 25045006
TI  - Human heart conjugate cooling simulation: unsteady thermo-fluid-stress analysis.
AB  - The main objective of this work was to demonstrate computationally that realistic
      human hearts can be cooled much faster by performing conjugate heat transfer
      consisting of pumping a cold liquid through the cardiac chambers and major veins
      while keeping the heart submerged in cold gelatin filling a cooling container.
      The human heart geometry used for simulations was obtained from three
      dimensional, high resolution CT-angio scans. Two fluid flow domains for the right
      (pulmonic) and left (systemic) heart circulations, and two solid domains for the
      heart tissue and gelatin solution were defined for multi-domain numerical
      simulation. Detailed unsteady temperature fields within the heart tissue were
      calculated during the conjugate cooling process. A linear thermoelasticity
      analysis was performed to assess the stresses applied on the heart due to the
      coolant fluid shear and normal forces and to examine the thermal stress caused by
      temperature variation inside the heart. It was demonstrated that a conjugate
      cooling effort with coolant temperature at +4 degrees C is capable of reducing
      the average heart temperature from +37 degrees C to +8 degrees C in 25 minutes
      for cases in which the coolant was steadily pumped only through major heart inlet
      veins and cavities.

PMID- 25045007
TI  - The mechanisms of oxygen reduction and evolution reactions in nonaqueous lithium
      oxygen batteries.
AB  - A fundamental understanding of the mechanisms of both the oxygen reduction
      reaction (ORR) and the oxygen evolution reaction (OER) in nonaqueous lithium
      oxygen (Li-O2) batteries is essential for the further development of these
      batteries. In this work, we systematically investigate the mechanisms of the
      ORR/OER reactions in nonaqueous Li-O2 batteries by using electron paramagnetic
      resonance (EPR) spectroscopy, using 5,5-dimethyl-pyrroline N-oxide as a spin
      trap. The study provides direct verification of the formation of the superoxide
      radical anion (O2(-)) as an intermediate in the ORR during the discharge process,
      while no O2(-) was detected in the OER during the charge process. These findings
      provide insight into, and an understanding of, the fundamental reaction
      mechanisms involving oxygen and guide the further development of this field.

PMID- 25045008
TI  - Novel coronene-naphthalene dimide-based donor-acceptor pair for tunable charge
      transfer nanostructures.
AB  - Charge-transfer (CT) assemblies of aromatic donor (D) and acceptor (A) molecules
      have recently gained attention as a promising material for organic electronics
      and ferroelectrics. Two major factors which govern their functions are the
      strength of CT interaction and their supramolecular nanostructuring. Here we
      present coronene-naphthalenediimide (NDI)-based novel D-A pairs that form
      alternately stacked CT assemblies. Through systematic substitution of the NDI
      derivatives and studying their CT interactions with coronene, a clear
      understanding of the secondary forces responsible for controlling their
      association is gained. Finally, the use of CT-based supramolecular amphiphiles
      for their nanostructural engineering into ordered one-dimensional (1-D)
      assemblies is demonstrated. 

PMID- 25045009
TI  - CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic
      resonance imaging.
AB  - MRI offers high spatial resolution with excellent tissue penetration but it has
      limited sensitivity and the commonly administered contrast agents lack
      specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were
      synthesized that were designed to selectively undergo copper-free click
      conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby
      leading to a self-assembled superparamagnetic nanocluster network with T2 signal
      enhancement properties. For this purpose, IONPs with bioorthogonal azide and
      alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4
      targeted peptide ligands were synthesized and characterized. The IONPs were
      tested in vitro and T2 signal enhancements of around 160 % were measured when the
      IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous
      systemic administration of the bioorthogonal IONPs in tumor-bearing mice
      demonstrated the signal-enhancing ability of these 'smart' self-assembling
      nanomaterials. 

PMID- 25045011
TI  - Effects of communication styles on marital satisfaction and distress of parents
      of pediatric cancer patients: a prospective longitudinal study.
AB  - OBJECTIVE: The aim of this study was to examine the longitudinal effects of
      communication styles on marital satisfaction and distress of parents of children
      treated for cancer. METHODS: Marital dissatisfaction (Maudsley Marital
      Questionnaire), intimacy, avoidance, destructive and incongruent communication
      (Communication Skills Inventory) and psychological distress (General Health
      Questionnaire) were assessed in 115 parents of pediatric cancer patients shortly
      after diagnosis (T1) and 5 years later (T2). RESULTS: Only mothers' marital
      dissatisfaction increased significantly over time. No gender differences in
      dissatisfaction were found. Mothers had a significantly higher lack of intimacy
      score than fathers. All T1 communication styles were significantly univariately
      related to fathers' and mothers' T2 marital dissatisfaction, while not to T2
      distress. Mothers' T1 marital dissatisfaction accounted for 67% and fathers' for
      12% in the explained variance of T2 dissatisfaction. T1 destructive communication
      uniquely affected fathers' T2 marital dissatisfaction and T1 avoidant
      communication that of mothers. CONCLUSIONS: Five years after cancer diagnosis in
      their children, the quality of parents' marital relationships seemed largely
      unchanged. Parents' use of communication skills at diagnosis appeared to have
      limited effect on their marital dissatisfaction and no effect on their distress 5
      years later. While avoidant communication seemed indicative of mothers' marital
      distress, fathers' seemed affected by destructive communication.

PMID- 25045010
TI  - Objects and landmarks: hippocampal place cells respond differently to
      manipulations of visual cues depending on size, perspective, and experience.
AB  - Human navigation studies show that landmarks are used for orientation, whereas
      objects contribute to the contextual representation of an environment. What
      constitutes a landmark? Classic rodent studies show that hippocampal place fields
      are controlled by distal, polarizing cues. Place fields, however, are also
      influenced by local cues. One difficulty in examining mechanisms by which distal
      and local cues influence the activity of hippocampal cells is that distant cues
      are necessarily processed visually, whereas local cues are generally multimodal.
      Here, we compared the effects of 90 degrees  rotations under different cue
      conditions in which cues were restricted to the visual modality. Three two
      dimensional visual cue conditions were presented in a square open field: a large
      vertical cue on one wall, a large floor cue in a corner abutting two walls, and a
      smaller complex floor cue in a corner adjacent to two walls. We show that
      rotations of large distal cues, whether on the wall or floor, were equally
      effective in controlling place fields. Rotations of the smaller floor cues were
      significantly more likely to result in remapping, whether or not animals were
      also exposed to the distal polarizing cues. Responses of distal and local cues
      were affected differently by extended experience. Our data provide evidence that
      hippocampal place cell responses to visual cues are influenced by perspective,
      salience of the cue, and prior experience. The hippocampus processes visual cues
      either as stable landmarks useful for orientation and navigation or as
      nonstationary objects or features of the local environment available for
      associative learning or binding items in context.

PMID- 25045012
TI  - Munchnones--new facets after 50 years.

PMID- 25045013
TI  - Highly efficient photocatalytic H2 evolution from water using visible light and
      structure-controlled graphitic carbon nitride.
AB  - The major challenge of photocatalytic water splitting, the prototypical reaction
      for the direct production of hydrogen by using solar energy, is to develop low
      cost yet highly efficient and stable semiconductor photocatalysts. Herein, an
      effective strategy for synthesizing extremely active graphitic carbon nitride (g
      C3N4) from a low-cost precursor, urea, is reported. The g-C3N4 exhibits an
      extraordinary hydrogen-evolution rate (ca. 20,000 MUmol h(-1) g(-1) under full
      arc), which leads to a high turnover number (TON) of over 641 after 6 h. The
      reaction proceeds for more than 30 h without activity loss and results in an
      internal quantum yield of 26.5% under visible light, which is nearly an order of
      magnitude higher than that observed for any other existing g-C3N4 photocatalysts.
      Furthermore, it was found by experimental analysis and DFT calculations that as
      the degree of polymerization increases and the proton concentration decreases,
      the hydrogen-evolution rate is significantly enhanced.

PMID- 25045014
TI  - A panel of protein markers for the early detection of lung cancer with bronchial
      brushing specimens.
AB  - BACKGROUND: To date, no robust biomarkers have been available in clinical
      practice that can provide an early diagnostic evaluation of lung cancer. The
      objective of this study was to identify potential biomarkers for the early
      detection of lung cancer using bronchial brushing specimens. METHODS:
      Immunocytochemistry was used to investigate the expression of 35 proteins in 880
      bronchial brushing specimens from both outpatients and inpatients who had either
      lung cancer or benign lung lesions. An optimal panel was identified that had high
      sensitivity and considerable specificity for detecting lung cancer. Associations
      between protein expression and clinicopathologic parameters were assessed.
      RESULTS: Tumor protein 53 (TP53), TP63, Ki67, epidermal growth factor receptor
      (EGFR), minichromosome maintenance complex component 6 (MCM6), MCM7,
      uncharacterized proteins KIAA1522 and KIAA0317, and ubiquitin-protein ligase UHR1
      (ICBP90) frequently presented high expression in bronchial brushing specimens
      from patients who had lung cancer compared with patients who had benign lung
      lesions. A 6-protein panel consisting of TP53, Ki67, MCM6, MCM7, KIAA1522, and
      KIAA0317 was identified as the best combination, with sensitivity of 81.1% (309
      of 381 specimens) for detecting nonsmall cell lung cancer (NSCLC) and 86.8% (145
      of 167 specimens) for detecting small cell lung cancer (SCLC) (specificity,
      83.3%; 65 of 78 specimens). The combination of cytology and the protein panel
      significantly improved the sensitivity of bronchial brushing examination for
      detecting lung cancer (P<.00001), which increased from 49.1% to 81% in early
      stage NSCLC (stage I and II). In combined analyses, the protein panel was
      positively associated with patient sex (P=.00033), tumor type (P<.00001), tumor
      location (P<.00001), and lymph node metastasis (P=.028). CONCLUSIONS: The 6
      protein panel is a potential biomarker for the early detection of lung cancer in
      bronchial brushings.

PMID- 25045016
TI  - Luminescence and spectroscopic studies of halosulfate phosphors: a review.
AB  - This review discusses the photoluminescence (PL) characteristics of halosulfate
      phosphors developed by us. Halosulfate phosphors KCaSO4 Cl:X,Y (X = Eu or Ce; Y =
      Dy or Mn) and Na6 (SO4 )2 FCl (doped with Dy, Ce or Eu) were prepared using a
      solid-state diffusion method. The mechanism of energy transfer from Eu(2+) 
      >Dy(3+) , Ce(3+) ->Dy(3+) and Ce(3+) ->Mn(2+) has also been studied. Dy(3+)
      emission in the host at 475 and 570 nm is observed due to (4) F9/2 ->(6) H15/2
      and (4) F9/2 ->(6) H13/2 transition, whereas the PL emission spectra of Na6 (SO4
      )2 FCl:Ce phosphor shows Ce(3+) emission at 322 nm due to 5d->4f transition of
      the Ce(3+) ion. The main property of KCaSO4 Cl is its very high sensitivity,
      particularly when doped by Dy, Mn or Pb activators. This review also discusses
      the PL characteristics of some new phosphors such as LiMgSO4 F, Na6 Pb4 (SO4 )6
      Cl2 , Na21 Mg(SO4 )10 Cl3 and Na15 (SO4 )5 F4 Cl.

PMID- 25045015
TI  - Transcription factor Sp4 regulates expression of nervous wreck 2 to control
      NMDAR1 levels and dendrite patterning.
AB  - Glutamatergic signaling through N-methyl-d-aspartate receptors (NMDARs) is
      important for neuronal development and plasticity and is often dysregulated in
      psychiatric disorders. Mice mutant for the transcription factor Sp4 have reduced
      levels of NMDAR subunit 1 (NR1) protein, but not mRNA, and exhibit behavioral and
      memory deficits (Zhou et al., [2010] Human Molecular Genetics 19: 3797-3805). In
      developing cerebellar granule neurons (CGNs), Sp4 controls dendrite patterning
      (Ramos et al., [2007] Proc Natl Acad Sci USA 104: 9882-9887). Sp4 target genes
      that regulate dendrite pruning or NR1 levels are not known. Here we report that
      Sp4 activates transcription of Nervous Wreck 2 (Nwk2; also known as Fchsd1) and,
      further, that Nwk2, an F-BAR domain-containing protein, mediates Sp4-dependent
      regulation of dendrite patterning and cell surface expression of NR1. Knockdown
      of Nwk2 in CGNs increased primary dendrite number, phenocopying Sp4 knockdown,
      and exogenous expression of Nwk2 in Sp4-depleted neurons rescued dendrite number.
      We observed that acute Sp4 depletion reduced levels of surface, but not total,
      NR1, and this was rescued by Nwk2 expression. Furthermore, expression of Nr1
      suppressed the increase in dendrite number in Sp4- or Nwk2- depleted neurons. We
      previously reported that Sp4 protein levels were reduced in cerebellum of
      subjects with bipolar disorder (BD) (Pinacho et al., [2011] Bipolar Disorders 13:
      474-485). Here we report that Nwk2 mRNA and NR1 protein levels were also reduced
      in postmortem cerebellum of BD subjects. Our data suggest a role for Sp4
      regulated Nwk2 in NMDAR trafficking and identify a Sp4-Nwk2-NMDAR1 pathway that
      regulates neuronal morphogenesis during development and may be disrupted in
      bipolar disorder.

PMID- 25045017
TI  - Real time fMRI feedback of the anterior cingulate and posterior insular cortex in
      the processing of pain.
AB  - Self-regulation of brain activation using real-time functional magnetic resonance
      imaging has been used to train subjects to modulate activation in various brain
      areas and has been associated with behavioral changes such as altered pain
      perception. The aim of this study was to assess the comparability of upregulation
      versus downregulation of activation in the rostral anterior cingulate cortex
      (rACC) and left posterior insula (pInsL) and its effect on pain intensity and
      unpleasantness. In a first study, we trained 10 healthy subjects to separately
      upregulate and downregulate the blood oxygenation level-dependent response in the
      rACC or pInsL (six trials on 4 days) in response to painful electrical
      stimulation. The participants learned to significantly downregulate activation in
      pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of
      one region and direction of the modulation was not significantly correlated with
      success in another condition, indicating that the ability to control pain-related
      brain activation is site-specific. Less covariation between the areas in response
      to the nociceptive stimulus was positively correlated with learning success.
      Upregulation or downregulation of either region was unrelated to pain intensity
      or unpleasantness; however, our subjects did not learn rACC upregulation, which
      might be important for pain control. A significant increase in pain
      unpleasantness was found during upregulation of pInsL when covariation with the
      rACC was low. These initial results suggest that the state of the network
      involved in the processing of pain needs to be considered in the modulation of
      pain-evoked activation and its behavioral effects.

PMID- 25045018
TI  - UTE imaging in the musculoskeletal system.
AB  - Tissues, such as bone, tendon, and ligaments, contain a high fraction of
      components with "short" and "ultrashort" transverse relaxation times and
      therefore have short mean transverse relaxation times. With conventional magnetic
      resonance imaging (MRI) sequences that employ relatively long echo times (TEs),
      there is no opportunity to encode the decaying signal of short and ultrashort T2
      /T2 * tissues before it has reached zero or near zero. The clinically compatible
      ultrashort TE (UTE) sequence has been increasingly used to study the
      musculoskeletal system. This article reviews the UTE sequence as well as various
      modifications that have been implemented since its introduction. These
      modifications have been used to improve efficiency or contrast as well as provide
      quantitative analysis. This article reviews several clinical musculoskeletal
      applications of UTE.

PMID- 25045021
TI  - The mitochondrial amidoxime reducing component (mARC): involvement in metabolic
      reduction of N-oxides, oximes and N-hydroxyamidinohydrazones.
AB  - The mitochondrial amidoxime reducing component (mARC) is a molybdenum-containing
      enzyme and capable of reducing N-hydroxylated structures such as amidoxime
      prodrugs. In this study, we tested the involvement of mARC in the reduction of N
      oxides (amitriptyline-N-oxide, nicotinamide-N-oxide), oximes ((E)-/(Z)-2,4,6
      trimethylacetophenonoxime) and a N-hydroxyamidinohydrazone (guanoxabenz). All
      groups are reduced by mARC proteins, and the enzymes are therefore involved in
      the interconversion of N-oxygenated metabolites originating from cytochrome P450s
      and flavin-containing monooxygenases. In addition, these structures open up
      further options for serving as prodrugs. Thus, with respect to these reactions,
      testing of candidates with N-oxygenated structures should not solely be carried
      out in microsomal enzyme sources but as well in mitochondria. However,
      differences in the reduction of oximes and N-oxides between the two isoforms,
      namely mARC1 and mARC2, were detectable; N-oxides are exclusively reduced by
      mARC1. We therefore assume differences between the so far unknown 3D structures
      of the two proteins. 

PMID- 25045020
TI  - Role of p53 in preadipocyte differentiation.
AB  - Insulin resistance, diabetes and many kinds of cancers are common in overweight
      and obese individuals. The tumor suppressor p53 is important in securing genetic
      stability, but its role in the regulation of metabolic processes and cell
      differentiation remains unclear. We have investigated the role of p53 in
      adipocyte differentiation. Using 3T3-L1 cells, a mouse embryonic fibroblast
      preadipocyte model and DIO rat model, p53 expression and function during
      adipocyte differentiation were investigated. p53 expression increased on the
      second and fourth day of adipocyte differentiation and decreased thereafter. Its
      overexpression in 3T3-L1 preadipocytes markedly reduced adipogenesis and marker
      gene expression. p53 activity was weakened in DIO rat abdominal adipose tissue
      because of an decreased expression of its activated phosphorylated form. In
      contrast, p53 knockout enhanced adipogenesis and the expression of marker genes,
      but significantly reduced insulin-stimulated Akt phosphorylation. These results
      indicate that p53 partly suppresses preadipocyte differentiation and adipogenesis
      by regulating adipocyte gene expression and Akt signaling.

PMID- 25045022
TI  - Charge asymmetry at aqueous hydrophobic interfaces and hydration shells.
AB  - Guilty as charged: Water is often modeled as a dielectric continuum, but the
      molecular structure of water is asymmetric. Two ions that have a virtually
      identical size, shape, and structure, but an opposite charge sign have been
      investigated to see whether charge makes a fundamental difference to water
      structuring. The spectroscopic data for the hydration and interface structures
      are found to be remarkably different for opposite charges. 

PMID- 25045019
TI  - Sensory hair cell regeneration in the zebrafish lateral line.
AB  - BACKGROUND: Damage or destruction of sensory hair cells in the inner ear leads to
      hearing or balance deficits that can be debilitating, especially in older adults.
      Unfortunately, the damage is permanent, as regeneration of the inner ear sensory
      epithelia does not occur in mammals. RESULTS: Zebrafish and other non-mammalian
      vertebrates have the remarkable ability to regenerate sensory hair cells and
      understanding the molecular and cellular basis for this regenerative ability will
      hopefully aid us in designing therapies to induce regeneration in mammals.
      Zebrafish not only possess hair cells in the ear but also in the sensory lateral
      line system. Hair cells in both organs are functionally analogous to hair cells
      in the inner ear of mammals. The lateral line is a mechanosensory system found in
      most aquatic vertebrates that detects water motion and aids in predator
      avoidance, prey capture, schooling, and mating. Although hair cell regeneration
      occurs in both the ear and lateral line, most research to date has focused on the
      lateral line due to its relatively simple structure and accessibility.
      CONCLUSIONS: Here we review the recent discoveries made during the
      characterization of hair cell regeneration in zebrafish.

PMID- 25045024
TI  - Lowest singlet exciton in pentacene: modern calculations versus classic
      experiments.
AB  - Based on simple model calculations, the expected magnitude of the field-induced
      shift observable in electroabsorption is estimated for three alternative
      assignments proposed in the literature for the lowest singlet excitation of the
      pentacene crystal (pure Frenkel exciton, pure charge-transfer exciton, or a
      mixture of both). The results are compared with the corresponding experimental
      value, which is also known from the literature. The latter turns out to be
      compatible only with the mixed parentage of the pertinent state, which contains
      the charge-transfer contribution in the range from 25 to 70%. The conclusion is
      discussed in the context of the present controversies concerning the existing
      experimental and theoretical evidence on this subject.

PMID- 25045023
TI  - Phenotypic expression in human monocyte-derived interleukin-4-induced foreign
      body giant cells and macrophages in vitro: dependence on material surface
      properties.
AB  - The effects of different material surfaces on phenotypic expression in
      macrophages and foreign body giant cells (FBGC) were addressed using our in vitro
      system of interleukin (IL)-4-induced macrophage fusion and FBGC formation.
      Arginine-glycine-aspartate (RGD)-, vitronectin (VN)-, and chitosan (CH)-adsorbed
      cell culture polystyrene, carboxylated (C, negatively charged) polystyrene, and
      unmodified (PS, non-cell culture treated) polystyrene were compared for their
      abilities to support monocyte/macrophage adhesion and IL-4-induced macrophage
      fusion. Pooled whole cell lysates from four different donors were evaluated by
      immunoblotting for expression of selected components in monocytes, macrophages,
      and FBGC. In addition to RGD and VN as previously shown, we find that CH supports
      macrophage adhesion and FBGC formation, whereas C or PS support macrophage
      adhesion but do not permit macrophage fusion under otherwise identical conditions
      of IL-4 stimulation. Likewise, components related to macrophage fusion (CD206,
      CD98, CD147, CD13) are strongly expressed on RGD-, VN-, and CH-adsorbed surfaces
      but are greatly diminished or not detected on C or PS. Importantly, material
      surfaces also influence the FBGC phenotype itself, as demonstrated by strong
      differences in patterns of expression of HLA-DR, B7-2, B7-H1, and toll-like
      receptor (TLR)-2 on RGD, VN, and CH despite morphologic similarities between FBGC
      on these surfaces. Likewise, we observe differences in the expression of B7-2,
      alpha2-macroglobulin, TLR-2, and fascin-1 between mononuclear macrophages on C
      and PS. Collectively, these findings reveal the extent to which material surface
      chemistry influences macrophage/FBGC phenotype beyond evident morphological
      similarities or differences and identify CH as an FBGC-supportive substrate.

PMID- 25045025
TI  - Mechanical properties of suture materials in general and cutaneous surgery.
AB  - Comprehensive studies comparing tensile properties of sutures are over 25 years
      old and do not include recent advances in suture materials. Accordingly, the
      objective of this article is to investigate the tensile properties of commonly
      used sutures in cutaneous surgery. Thirteen 3-0 sized modern sutures (four
      nonabsorbable and nine absorbable) were tensile tested in both straight and
      knotted configurations according to the procedures outlined by the United States
      Pharmacopeia. Glycomer 631 was found to have the highest failure load (56.1 N) of
      unknotted absorbable sutures, while polyglyconate (34.2 N) and glycomer 631 (34.3
      N) had the highest failure loads of knotted absorbable sutures. Nylon (30.9 N)
      and polypropylene (18.9 N) had the greatest failure loads of straight and knotted
      nonabsorbable sutures, respectively. Polydioxane was found to have the most
      elongation prior to breakage (144%) of absorbable sutures. Silk (8701 MPa) and
      rapid polyglactin 910 (9320 MPa) had the highest initial modulus of nonabsorbable
      and absorbable sutures, respectively. The new data presented in the study provide
      important information for guiding the selection of suture materials for specific
      surgeries.

PMID- 25045026
TI  - Fetal akinesia deformation sequence: expanding the phenotypic spectrum.
AB  - We report on two unrelated fetuses born to nonconsanguineous couples with fetal
      akinesia deformation sequence (FADS). The fetuses shared facial features,
      micrognathia, fetal finger pads, bulbous digital tips, pterygia, clubfeet,
      ventriculomegaly, and cerebellar anomalies. Both had loss/absence of Purkinje
      cells in cerebellum. The first family had a similarly affected previous pregnancy
      suggesting an autosomal recessive inheritance. The second fetus, in addition to
      the findings in the first, had cleft palate and defective lobulation of lungs.
      These fetuses appear to have the Pena-Shokeir phenotype (PSP) or FADS. These two
      cases seem to define a newly recognizable subtype of FADS with bulbous digital
      tips, prominent digit pads and cerebellar anomalies, and highlight the phenotypic
      diversity of syndromes with multiple congenital contractures manifesting in
      utero.

PMID- 25045027
TI  - Plasmon-induced ammonia synthesis through nitrogen photofixation with visible
      light irradiation.
AB  - We have successfully developed a plasmon-induced technique for ammonia synthesis
      that responds to visible light through a strontium titanate (SrTiO3)
      photoelectrode loaded with gold (Au) nanoparticles. The photoelectrochemical
      reaction cell was divided into two chambers to separate the oxidized (anodic
      side) and reduced (cathodic side) products. To promote NH3 formation, a chemical
      bias was applied by regulating the pH value of these compartments, and ethanol
      was added to the anodic chamber as a sacrificial donor. The quantity of NH3
      formed at the ruthenium surface, which was used as a co-catalyst for SrTiO3,
      increases linearly as a function of time under irradiation with visible light at
      wavelengths longer than 550 nm. The NH3 formation action spectrum approximately
      corresponds to the plasmon resonance spectrum. We deduced that plasmon-induced
      charge separation at the Au/SrTiO3 interface promotes oxidation at the anodic
      chamber and subsequent nitrogen reduction on the cathodic side.

PMID- 25045028
TI  - Changing from a traditional psychodynamic treatment programme to mentalization
      based treatment for patients with borderline personality disorder--does it make a
      difference?
AB  - OBJECTIVES: Few studies outside United Kingdom have documented effects of
      mentalization-based treatment (MBT) for patients with borderline personality
      disorder (BPD). This study aimed to investigate outcomes for BPD patients treated
      in an MBT programme in a Norwegian specialist treatment unit and compare benefits
      of the implemented MBT with the unit's former psychodynamic treatment programme.
      DESIGN: A naturalistic, longitudinal, comparison of treatment effects for BPD
      patients before and after transition to MBT. METHODS: The sample consisted of 345
      BPD patients treated in the period 1993-2013. Before 2008, patients were admitted
      to a psychodynamic treatment programme (n = 281), after 2008 patients received
      MBT (n = 64). Symptom distress, interpersonal problems, and global functioning
      were assessed repeatedly throughout the treatment. Suicidal/self-harming acts,
      hospital admissions, medication, and occupational status were assessed at the
      start and end of treatment. Therapists' competence and adherence to MBT was rated
      and found satisfactory. The statistical method for longitudinal analyses was
      mixed models. RESULTS: BPD patients in MBT and in the former psychodynamic
      treatment programme had comparable baseline severity and impairments of
      functioning. BPD patients in MBT had a remarkably low drop-out rate (2%),
      significantly lower than the former treatment. Improvements of symptom distress,
      interpersonal, global and occupational functioning were significantly greater for
      MBT patients. Large reductions in suicidal/self-harming acts, hospital
      admissions, and use of medication were evident in the course of both treatments.
      CONCLUSIONS: The study confirms the effectiveness of MBT for BPD patients and
      indicates greater clinical benefits than in traditional psychodynamic treatment
      programmes. PRACTITIONER POINTS: MBT is an effective treatment for patients with
      BPD. MBT can successfully be implemented in therapeutic settings outside United
      Kingdom and may be more beneficial than psychodynamic treatment programmes for
      BPD patients.

PMID- 25045029
TI  - Population pharmacokinetics of maslinic acid, a triterpene from olives, after
      intravenous and oral administration in rats.
AB  - SCOPE: Maslinic acid is a bioactive minor component of Olea europaea L. with
      health-enhancing activities and no harmful effects. A pharmacokinetic (PK) study
      was conducted to determine its bioavailability for future studies of maslinic
      acid in humans. METHODS AND RESULTS: Intravenous (1 mg/kg) and oral (50 mg/kg)
      administrations to Sprague-Dawley rats were performed. Blood was obtained several
      times over 24 h and PKs were analyzed with NONMEM 7.2, applying a population
      approach. Body weight was included a priori in the model with fixed allometric
      exponents, based on allometric principles. Plasma concentrations versus time were
      best characterized by a two-open compartment model with first-order absorption
      and linear elimination. Maslinic acid had a relative rapid oral absorption with a
      peak concentration after administration at 0.51 h and a bioavailability of 5.13%.
      Once in bloodstream, it distributed extensively into tissues, since the central
      and peripheral distribution volumes were 8.41 L/70 kg and 63.6 L/70 kg,
      respectively. The clearance (8 L/h/70 kg) was related to unaltered renal
      excretion. The prediction-corrected visual predictive check confirmed its
      stability and predictive ability. CONCLUSION: An allometric population PK model
      was performed for maslinic acid, which adequately described and predicted plasma
      concentrations.

PMID- 25045030
TI  - alpha-lipoic acid reduces fatty acid esterification and lipogenesis in adipocytes
      from overweight/obese subjects.
AB  - OBJECTIVE: alpha-Lipoic acid (alpha-LA) is a natural occurring antioxidant with
      beneficial effects on obesity. The aim of this study was to investigate the
      putative effects of alpha-LA on triglyceride accumulation and lipogenesis in
      subcutaneous adipocytes from overweight/obese subjects and to determine the
      potential mechanisms involved. METHODS: Fully differentiated human subcutaneous
      adipocytes were treated with alpha-LA (100 and 250 uM) during 24 h for studying
      triglyceride content, de novo lipogenesis, and levels of key lipogenic enzymes.
      The involvement of AMP-activated protein kinase (AMPK) activation was also
      evaluated. RESULTS: alpha-LA down-regulated triglyceride content by inhibiting
      fatty acid esterification and de novo lipogenesis. These effects were mediated by
      reduction in fatty acid synthase (FAS), stearoyl-coenzyme A desaturase 1, and
      diacylglycerol O-acyltransferase 1 protein levels. Interestingly, alpha-LA
      increased AMPK and acetyl CoA carboxylase phosphorylation, while the presence of
      the AMPK inhibitor Compound C reversed the inhibition observed on FAS protein
      levels. CONCLUSIONS: alpha-LA down-regulates key lipogenic enzymes, inhibiting
      lipogenesis and reducing triglyceride accumulation through the activation of AMPK
      signaling pathway in human subcutaneous adipocytes from overweight/obese
      subjects.

PMID- 25045031
TI  - N-trifluoromethylthiosaccharin: an easily accessible, shelf-stable, broadly
      applicable trifluoromethylthiolating reagent.
AB  - A new, electrophilic trifluoromethylthiolating reagent, N
      trifluoromethylthiosaccharin, was developed and can be synthesized in two steps
      from saccharin within 30 minutes. N-trifluoromethylthiosaccharin is a powerful
      trifluoromethylthiolating reagent and allows the trifluoromethylthiolation of a
      variety of nucleophiles such as alcohols, amines, thiols, electron-rich arenes,
      aldehydes, ketones, acyclic beta-ketoesters, and alkynes under mild reaction
      conditions. 

PMID- 25045032
TI  - Cell surface display yields evolvable, clickable antibody fragments.
AB  - Non-canonical amino acids (ncAAs) provide powerful tools for engineering the
      chemical and physical properties of proteins. However, introducing ncAAs into
      proteins can affect protein properties in unpredictable ways, thus necessitating
      screening efforts to identify mutants with desirable properties. In this work, we
      describe an Escherichia coli cell surface display platform for the directed
      evolution of clickable antibody fragments. This platform enabled isolation of
      antibody fragments with improved digoxigenin binding and modest affinity
      maturation in several different ncAA contexts. Azide-functionalized fragments
      exhibited improved binding kinetics relative to their methionine counterparts,
      facile chemical modification through azide-alkyne cycloaddition, and retention of
      binding properties after modification. The results described here suggest new
      possibilities for protein engineering, including modulation of molecular
      recognition events by ncAAs and direct screening of libraries of chemically
      modified proteins. 

PMID- 25045033
TI  - Apert syndrome with omphalocele: a case report.
AB  - Apert syndrome is a genetic disorder known as acrocephalopolysyndactyly type 1
      caused by mutations in the fibroblast growth factor receptor 2 and characterized
      by coronal craniosynostosis, symmetric bone and skin syndactyly of hands and
      feet, and craniofacial dysmorphic features. The estimated prevalence of this
      syndrome is 10 to 15.5 cases per 1,000,000 live births. Apert syndrome has
      considerable clinical variability. We present a case of Apert syndrome and
      associated features reported to the National Registry of Congenital Anomalies of
      Argentina (RENAC). The reported case had omphalocele, esophageal atresia, and
      mega cisterna magna. The last two signs were reported several times as part of
      the clinical presentation of Apert syndrome. To our knowledge, this is the second
      reported case diagnosed with Apert syndrome associated with omphalocele.

PMID- 25045034
TI  - Evaluation of a novel methacrylate-based Protein A resin for the purification of
      immunoglobulins and Fc-fusion proteins.
AB  - Protein A affinity chromatography is a central part of most commercial monoclonal
      antibody and Fc-fusion protein purification processes. In the last couple years
      an increasing number of new Protein A technologies have emerged. One of these new
      Protein A technologies consists of a novel, alkaline-tolerant, Protein A ligand
      coupled to a macroporous polymethacrylate base matrix that has been optimized for
      immunoglobulin (Ig) G capture. The resin is interesting from a technology
      perspective because the particle size and pore distribution of the base beads are
      reported to have been optimized for high IgG binding and fast mass transfer,
      while the Protein A ligand has been engineered for enhanced alkaline tolerance.
      This resin was subjected to a number of technical studies including evaluating
      dynamic and static binding capacities, alkaline stability, Protein A leachate
      propensity, impurity clearance, and pressure-flow behavior. The results
      demonstrated similar static binding capacities as those achieved with industry
      standard agarose Protein A resins, but marginally lower dynamic binding
      capacities. Removal of impurities from the process stream, particularly host cell
      proteins, was molecule dependent, but in most instances matched the performance
      of the agarose resins. This resin was stable in 0.1 M NaOH for at least 100 h
      with little loss in binding capacity, with Protein A ligand leakage levels
      comparable to values for the agarose resins. Pressure-flow experiments in lab
      scale chromatography columns demonstrated minimal resin compression at typical
      manufacturing flow rates. Prediction of resin compression in manufacturing scale
      columns did not suggest any pressure limitations upon scale up.

PMID- 25045035
TI  - Improving hand functional use in subjects with multiple sclerosis using a musical
      keyboard: a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Playing an instrument implies neuroplasticity in
      different cerebral regions. This phenomenon has been described in subjects with
      stroke, suggesting that it could play a role in hand rehabilitation. The aim of
      this study is to analyse the effectiveness of playing a musical keyboard in
      improving hand function in subjects with multiple sclerosis. METHODS: Nineteen
      hospitalized subjects were randomized in two groups: nine played a turned-on
      musical keyboard by sequences of fingers movements (audio feedback present) and
      10 performed the same exercises on a turned-off musical keyboard (audio feedback
      absent). Training duration was half an hour per day for 15 days. Primary outcome
      was the perceived hand functional use measured by ABILHAND Questionnaire.
      Secondary outcomes were hand dexterity, measured by Nine-Hole Peg Test, and hand
      strength, measured by Jamar and Pinch dynamometers. Two-way analysis of variance
      was used for data analysis. RESULTS: The interaction time * group was significant
      (p = 0.003) for ABILHAND Questionnaire in favour of experimental group (mean
      between-group difference 0.99 logit [IC95%: 0.44; 1.54]). The two groups showed a
      significant time effect for all outcomes except for Jamar measure. DISCUSSION:
      Playing a musical keyboard seems a valid method to train the functional use of
      hands in subjects with multiple sclerosis.

PMID- 25045036
TI  - Antinociceptive activity of the new triple reuptake inhibitor NS18283 in a mouse
      model of chemotherapy-induced neuropathic pain.
AB  - BACKGROUND: Chronic neuropathic pain can lead to anxiety and depression. Drugs
      that block reuptake of serotonin, norepinephrine and/or dopamine are widely used
      to treat depression, and have emerged as useful drugs in the treatment of
      neuropathic pain. This study compared the acute antinociceptive effects of
      NS18283, a novel triple monoamine reuptake inhibitor (MRI) with indatraline,
      venlafaxine and escitalopram in a mouse model of neuropathic pain. METHOD:
      Neuropathic pain-like behaviours were induced in mice by repeated injections of
      oxaliplatin (OXA), and assessed using the von Frey hair test, the cold plate test
      and the thermal preference plate test. Anxio/depressive phenotype and
      antidepressant-like properties of compounds were assessed by the novelty
      suppressed feeding test and the tail suspension test, respectively. RESULTS: In
      vivo microdialysis experiments showed that each MRI increased extracellular
      serotonin, norepinephrine and/or dopamine levels in the cingulate cortex, in
      agreement with their in vitro reuptake inhibitory properties. Indatraline (3
      mg/kg) reversed the full repertoire of OXA-induced neuropathic hypersensitivity.
      NS18283 (10 mg/kg) reversed OXA-induced mechano-hypersensitivity and cold
      allodynia. Venlafaxine (16 mg/kg) and escitalopram (4 mg/kg) only reversed cold
      allodynia and mechano-hypersensitivity, respectively. All MRIs produced
      antidepressant-like activity in anxio/depressive phenotype of OXA mice.
      CONCLUSIONS: Acute administration of drugs that enhance the activity of
      serotonin, norepinephrine and dopamine neurotransmission within nociceptive
      pathways may provide a broader spectrum of antinociception than dual or selective
      reuptake inhibitors in animal models of neuropathic pain. Whether similar
      observations would occur after repeated administration of such compounds in an
      attempt to simulate dosing in humans, or be compromised by dopaminergic-mediated
      adverse effects warrants further investigation.

PMID- 25045038
TI  - The European Molecular Biology Laboratory (EMBL)--its anniversary and its
      chemistry.

PMID- 25045037
TI  - Synthesis of (+)-discodermolide by catalytic stereoselective borylation
      reactions.
AB  - The marine natural product (+)-discodermolide was first isolated in 1990 and, to
      this day, remains a compelling synthesis target. Not only does the compound
      possess fascinating biological activity, but it also presents an opportunity to
      test current methods for chemical synthesis and provides an inspiration for new
      reaction development. A new synthesis of discodermolide employs a previously
      undisclosed stereoselective catalytic diene hydroboration and also establishes a
      strategy for the alkylation of chiral enolates. Furthermore, this synthesis of
      discodermolide provides the first examples of the asymmetric 1,4-diboration of
      dienes and borylative diene-aldehyde couplings in complex-molecule synthesis. 

PMID- 25045039
TI  - Cadmium sulfide quantum dots supported on gallium and indium oxide for visible
      light-driven hydrogen evolution from water.
AB  - In this work, CdS quantum dots (QDs) supported on Ga2O3 and In2O3 are applied for
      visible-light-driven H2 evolution from aqueous solutions that contain lactic
      acid. With Pt as the cocatalyst, the H2 evolution rates on CdS/Pt/Ga2O3 and
      CdS/Pt/In2O3 are as high as 995.8 and 1032.2 MUmol h(-1), respectively, under
      visible light (lambda>420 nm) with apparent quantum efficiencies of 43.6 and
      45.3% obtained at 460 nm, respectively. These are much higher than those on
      Pt/CdS (108.09 MUmol h(-1)), Pt/Ga2O3 (0.12 MUmol h(-1)), and Pt/In2O3 (0.05
      MUmol h(-1)). The photocatalysts have been characterized thoroughly and their
      band structures and photocurrent responses have been measured. The band alignment
      between the CdS QDs and In2O3 can lead to interfacial charge separation, which
      cannot occur between the CdS QDs and Ga2O3. Among the various possible factors
      that contribute to the high H2 evolution rates on CdS/Pt/oxide, the surface
      properties of the metal oxides play important roles, which include (i) the
      anchoring of CdS QDs and Pt nanoparticles for favorable interactions and (ii) the
      efficient trapping of photogenerated electrons from the CdS QDs because of
      surface defects (such as oxygen defects) based on photoluminescence and
      photocurrent studies.

PMID- 25045040
TI  - On the formation of a protic ionic liquid in nature.
AB  - The practical utility of ionic liquids (ILs) makes the absence (heretofore) of
      reported examples from nature quite puzzling, given the facility with which
      nature produces many other types of exotic but utilitarian substances. In that
      vein, we report here the identification and characterization of a naturally
      occurring protic IL. It can be formed during confrontations between the ants S.
      invicta and N. fulva. After being sprayed with alkaloid-based S. invicta venom,
      N. fulva detoxifies by grooming with its own venom, formic acid. The mixture is a
      viscous liquid manifestly different from either of the constituents. Further, we
      find that the change results as a consequence of formic acid protonation of the N
      centers of the S. invicta venom alkaloids. The resulting mixed-cation ammonium
      formate milieu has properties consistent with its classification as a protic IL. 

PMID- 25045041
TI  - Volumetric PET/CT parameters predict local response of head and neck squamous
      cell carcinoma to chemoradiotherapy.
AB  - It is not well established whether pretreatment (18) F-FDG PET/CT can predict
      local response of head and neck squamous cell carcinoma (HNSCC) to
      chemoradiotherapy (CRT). We examined 118 patients: 11 with nasopharyngeal cancer
      (NPC), 30 with oropharyngeal cancer (OPC), and 77 with laryngohypopharyngeal
      cancer (LHC) who had completed CRT. PET/CT parameters of primary tumor, including
      metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and mean
      standardized uptake value (SUVmax and SUVmean ), were correlated with local
      response, according to primary site and human papillomavirus (HPV) status.
      Receiver-operating characteristic analyses were made to access predictive values
      of the PET/CT parameters, while logistic regression analyses were used to
      identify independent predictors. Area under the curve (AUC) of the PET/CT
      parameters ranged from 0.53 to 0.63 in NPC and from 0.50 to 0.54 in OPC. HPV
      negative OPC showed AUC ranging from 0.51 to 0.58, while all of HPV-positive OPCs
      showed complete response. In contrast, AUC ranged from 0.71 to 0.90 in LHC.
      Moreover, AUCs of MTV and TLG were significantly higher than those of SUVmax and
      SUVmean (P < 0.01). After multivariate analysis, high MTV >25.0 mL and high TLG
      >144.8 g remained as independent, significant predictors of incomplete response
      compared with low MTV (odds ratio [OR], 13.4; 95% confidence interval [CI], 2.5
      72.9; P = 0.003) and low TLG (OR, 12.8; 95% CI, 2.4-67.9; P = 0.003),
      respectively. In conclusion, predictive efficacy of pretreatment (18) F-FDG
      PET/CT varies with different primary sites and chosen parameters. Local response
      of LHC is highly predictable by volume-based PET/CT parameters. 

PMID- 25045042
TI  - A rhodamine-based fluorescent probe for Cu(II) determination in aqueous solution.
AB  - An 'off-on' rhodamine-based fluorescence probe for the selective detection of
      Cu(II) has been designed, exploiting the guest-induced structure transform
      mechanism. This system shows a sharp Cu(II)-selective fluorescence enhancement
      response in an aqueous system under physiological pH, and possesses high
      selectivity against a background of environmentally and biologically relevant
      metal ions. Under optimum conditions, the fluorescence intensity enhancement of
      this system is linearly proportional to the Cu(II) concentration from 50 nM to
      6.0 MUM with a detection limit of 29 nM.

PMID- 25045043
TI  - Defective alpha-Fe2O3(0001): an ab initio study.
AB  - By using density functional theory calculations at the PBE+U level, we
      investigated the properties of hematite (0001) surfaces decorated with
      adatoms/vacancies/substituents. For the most stable surface termination over a
      large range of oxygen chemical potentials (muO), the vacancy formation and
      adsorption energies were determined as a function of muO. Under oxygen-rich
      conditions, all defects are metastable with respect to the ideal surface. Under
      oxygen-poor conditions, O vacancies and Fe adatoms become stable. Under ambient
      conditions, all defects are metastable; in the bulk, O vacancies form more easily
      than Fe vacancies, whereas at the surface the opposite is true. All defects, that
      is, O and Fe vacancies, Fe and Al adatoms, and Al substituents, induce important
      modifications to the geometry of the surface in their vicinity. Dissociative
      adsorption of molecular oxygen is likely to be exothermic on surfaces with Fe/Al
      adatoms or O vacancies.

PMID- 25045044
TI  - Mitochondrial tricarboxylate and dicarboxylate-tricarboxylate carriers: from
      animals to plants.
AB  - The citrate carrier (CiC), characteristic of animals, and the dicarboxylate
      tricarboxylate carrier (DTC), characteristic of plants and protozoa, belong to
      the mitochondrial carrier protein family whose members are responsible for the
      exchange of metabolites, cofactors, and nucleotides between the cytoplasm and the
      mitochondrial matrix. Most of the functional data on these transporters are
      obtained from the studies performed with the protein purified from rat, eel
      yeast, and maize mitochondria or recombinant proteins from different sources
      incorporated into phospholipid vesicles (liposomes). The functional data indicate
      that CiC is responsible for the efflux of acetyl-CoA from the mitochondria to the
      cytosol in the form of citrate, the primer for fatty acid, cholesterol synthesis,
      and histone acetylation. Like the CiC, the citrate exported by DTC from the
      mitochondria to the cytosol in exchange for oxaloacetate can be cleaved by
      citrate lyase to acetyl-CoA and oxaloacetate and used for fatty acid elongation
      and isoprenoid synthesis. In addition to its role in fatty acid synthesis, CiC is
      involved in other processes such as gluconeogenesis, insulin secretion,
      inflammation, and cancer progression, whereas DTC is involved in the production
      of glycerate, nitrogen assimilation, ripening of fruits, ATP synthesis, and
      sustaining of respiratory flux in fruit cells. This review provides an assessment
      of the current understanding of CiC and DTC structural and biochemical
      characteristics, underlying the structure-function relationship of these
      carriers. Furthermore, a phylogenetic relationship between CiC and DTC is
      proposed.

PMID- 25045045
TI  - Direct observation of liquid crystals using cryo-TEM: specimen preparation and
      low-dose imaging.
AB  - Liquid crystals (LCs) represent a challenging group of materials for direct
      transmission electron microscopy (TEM) studies due to the complications in
      specimen preparation and the severe radiation damage. In this paper, we summarize
      a series of specimen preparation methods, including thin film and cryo-sectioning
      approaches, as a comprehensive toolset enabling high-resolution direct cryo-TEM
      observation of a broad range of LCs. We also present comparative analysis using
      cryo-TEM and replica freeze-fracture TEM on both thermotropic and lyotropic LCs.
      In addition to the revisits of previous practices, some new concepts are
      introduced, e.g., suspended thermotropic LC thin films, combined high-pressure
      freezing and cryo-sectioning of lyotropic LCs, and the complementary applications
      of direct TEM and indirect replica TEM techniques. The significance of
      subnanometer resolution cryo-TEM observation is demonstrated in a few important
      issues in LC studies, including providing direct evidences for the existence of
      nanoscale smectic domains in nematic bent-core thermotropic LCs, comprehensive
      understanding of the twist-bend nematic phase, and probing the packing of
      columnar aggregates in lyotropic chromonic LCs. Direct TEM observation opens ways
      to a variety of TEM techniques, suggesting that TEM (replica, cryo, and in situ
      techniques), in general, may be a promising part of the solution to the lack of
      effective structural probe at the molecular scale in LC studies.

PMID- 25045046
TI  - Melatonin administered during the fetal stage affects circadian clock in the
      suprachiasmatic nucleus but not in the liver.
AB  - The mammalian circadian system develops gradually during ontogenesis, and after
      birth, the system is already set to a phase of the mothers. The role of maternal
      melatonin in the entrainment of fetal circadian clocks has been suggested, but
      direct evidence is lacking. In our study, intact or pinealectomized pregnant rats
      were exposed to constant light (LL) throughout pregnancy to suppress the
      endogenous melatonin and behavioral rhythms. During the last 5 days of gestation,
      the rats were injected with melatonin or vehicle or were left untreated. After
      delivery, daily expression profiles of c-fos and Avp in the suprachiasmatic
      nuclei (SCN), and Per1, Per2, Rev-erbalpha, and Bmal1 in the liver were measured
      in 1-day-old pups. Due to the LL exposure, no gene expression rhythms were
      detected in the SCN of untreated pregnant rats or in the SCN and liver of the
      pups. The administration of melatonin to pregnant rats entrained the pups' gene
      expression profiles in the SCN, but not in the liver. Melatonin did not affect
      the maternal behavior during pregnancy. Vehicle injections also synchronized the
      gene expression in the SCN but not in the liver. Melatonin and vehicle entrained
      the gene expression profiles to different phases, demonstrating that the effect
      of melatonin was apparently not due to the treatment procedure per se. The data
      demonstrate that in pregnant rats with suppressed endogenous melatonin levels,
      pharmacological doses of melatonin affect the fetal clock in the SCN but not in
      the liver.

PMID- 25045047
TI  - Hippocampal-parietal dysconnectivity and glutamate abnormalities in unmedicated
      patients with schizophrenia.
AB  - Abnormalities in resting state connectivity in schizophrenia (SZ) are now well
      established, but the biological substrates of these functional alterations remain
      to be elucidated. We performed a combined functional magnetic resonance imaging
      and magnetic resonance spectroscopy study in 22 unmedicated patients with SZ and
      22 matched healthy controls (HCs) to evaluate resting state functional
      connectivity of the hippocampus and Glx/Cr (a combined glutamate + glutamine peak
      normalized to creatine) in the hippocampus and investigate functional and
      neurometabolic abnormalities and examine the relationship between these.
      Functional connectivity between the left hippocampus and bilateral precuneus was
      significantly decreased in unmedicated patients with SZ when compared to HCs
      [t(4.22), cluster extent (kE) = 751, PFDRcorr  = 0.001, Montreal Neurological
      Institute coordinates: x = -4, y = -56, z = 44]. Glx/Cr in the hippocampus was
      significantly elevated in SZ (HC: mean = 0.60+/-0.10 SZ: 0.67+/-0.10; F = 5.742;
      P = 0.02), but was not correlated with functional connectivity deficits (P >
      0.05). In this study, we found hippocampal resting state functional connectivity
      deficits to the precuneus in unmedicated patients with SZ and an increase of
      Glx/Cr in the hippocampus, but did not observe a direct relationship between
      these abnormalities. However, our findings do not exclude the possibility of a
      shared underlying pathology, which warrants further investigation.

PMID- 25045048
TI  - Quantification of physiological levels of vitamin D3 and 25-hydroxyvitamin D3 in
      porcine fat and liver in subgram sample sizes.
AB  - Most methods for the quantification of physiological levels of vitamin D3 and 25
      hydroxyvitamin D3 are developed for food analysis where the sample size is not
      usually a critical parameter. In contrast, in life science studies sample sizes
      are often limited. A very sensitive liquid chromatography with tandem mass
      spectrometry method was developed to quantify vitamin D3 and 25-hydroxyvitamin D3
      simultaneously in porcine tissues. A sample of 0.2-1 g was saponified followed by
      liquid-liquid extraction and normal-phase solid-phase extraction. The analytes
      were derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione to improve the
      ionization efficiency by electrospray ionization. The method was validated in
      porcine liver and adipose tissue, and the accuracy was determined to be 72-97%
      for vitamin D3 and 91-124% for 25-hydroxyvitamin D3 . The limit of quantification
      was <0.1 ng/g, and the precision varied between 1.4 and 16% depending on the
      level of spiking. The small sample size required for the described method enables
      quantification of vitamin D3 and 25-hydroxyvitamin D3 in tissues from studies
      where sample sizes are limited. 

PMID- 25045049
TI  - Green acetylation of solketal and glycerol formal by heterogeneous acid catalysts
      to form a biodiesel fuel additive.
AB  - A glut of glycerol has formed from the increased production of biodiesel, with
      the potential to integrate the supply chain by using glycerol additives to
      improve biodiesel properties. Acetylated acetals show interesting cold flow and
      viscosity effects. Herein, a solventless heterogeneously catalyzed process for
      the acetylation of both solketal and glycerol formal to new products is
      demonstrated. The process is optimized by studying the effect of acetylating
      reagent (acetic acid and acetic anhydride), reagent molar ratios, and a variety
      of commercial solid acid catalysts (Amberlyst-15, zeolite Beta, K-10
      Montmorillonite, and niobium phosphate) on the conversion and selectivities. High
      conversions (72-95%) and selectivities (86-99%) to the desired products results
      from using acetic anhydride as the acetylation reagent and a 1:1 molar ratio with
      all catalysts. Overall, there is a complex interplay between the solid catalyst,
      reagent ratio, and acetylating agent on the conversion, selectivities, and
      byproducts formed. The variations are discussed and explained in terms of
      reactivity, thermodynamics, and reaction mechanisms. An alternative and efficient
      approach to the formation of 100% triacetin involves the ring-opening, acid
      catalyzed acetylation from solketal or glycerol formal with excesses of acetic
      anhydride.

PMID- 25045050
TI  - Diels-Alder reaction on free C68 fullerene and endohedral Sc3N@C68 fullerene
      violating the isolated pentagon rule: importance of pentagon adjacency.
AB  - The reaction mechanism and regioselectivity of the Diels-Alder reactions of C68
      and Sc3N@C68, which violate the isolated pentagon rule, were studied with density
      functional theory calculations. For C68, the [5,5] bond is the most favored
      thermodynamically, whereas the cycloaddition on the [5,6] bond has the lowest
      activation energy. Upon encapsulation of the metallic cluster, the exohedral
      reactivity of Sc3N@C68 is reduced remarkably owing to charge transfer from the
      cluster to the fullerene cage. The [5,5] bond becomes the most reactive site
      thermodynamically and kinetically. The bonds around the pentagon adjacency show
      the highest chemical reactivity, which demonstrates the importance of pentagon
      adjacency. Furthermore, the viability of Diels-Alder cycloadditions of several
      dienes and Sc3N@C68 was examined theoretically. o-Quinodimethane is predicted to
      react with Sc3N@C68 easily, which implies the possibility of using Diels-Alder
      cycloaddition to functionalize Sc3N@C68.

PMID- 25045051
TI  - [HCo(CO)4]-catalyzed three-component cycloaddition of epoxides, imines, and
      carbon monoxide: facile construction of 1,3-oxazinan-4-ones.
AB  - The three-component [3+2+1] cycloaddition of epoxides, imines, and carbon
      monoxide to produce 1,3-oxazinan-4-ones has been developed by using [HCo(CO)4] as
      the catalyst. The reaction occurs for a wide variety of imines and epoxides,
      under 60 bar of CO pressure at 50  degrees C, to produce 1,3-oxazinan-4-ones with
      different substitution patterns in high yields, and provides an efficient and
      atom-economic route to heterocycles from simple and readily available starting
      materials. A plausible mechanism involves [HCo(CO)4]-induced ring-opening of the
      epoxide, followed by sequential addition of carbon monoxide and the imine, and
      then ring closure to form the product accompanied by regeneration of [HCo(CO)4].

PMID- 25045052
TI  - Prevalence and risk factors of depressive disorder in caregivers of patients with
      head and neck cancer.
AB  - OBJECTIVE: The purpose of this study is to examine the prevalence and risk
      factors of depressive disorder in caregivers of patients with head and neck
      cancer. METHODS: Study subjects were recruited from a multidisciplinary
      outpatient clinic for head and neck cancer in a medical center from February to
      July 2012. Caregivers of patients with head and neck cancer were enrolled and
      assessed using the Structured Clinical Interview for the DSM-IV, Clinician
      Version, the Short Form 36 Health Survey, and the Family APGAR index. The main
      aim of the study was to examine the difference in demographic data and clinical
      characteristics between the caregivers with and without depressive disorders. In
      addition, a stepwise forward model of logistic regression was used to test the
      possible risk factors. RESULTS: One hundred and forty-three caregivers were
      included in the study. The most prevalent psychiatric disorder was depressive
      disorder (14.7%), followed by adjustment disorder (13.3%). Nearly one-third of
      the caregivers had a psychiatric diagnosis. By using logistic regression
      analysis, it was found that unemployment (odds ratio (OR) = 3.16; 95% CI, 1.04
      9.68), lower social functioning (OR = 1.43; 95% CI, 1.18-1.72), and lower
      educational level (OR = 1.16; 95% CI, 1.01-1.34) were significant risk factors
      for the depressive disorder. CONCLUSIONS: The clinical implication of our results
      is the value of using the standardized structured interview for early diagnosis
      of depressive disorder in caregivers of head and neck cancer patients. Early
      screening and management of depression in these caregivers will raise their
      quality of life and capability to care patients.

PMID- 25045053
TI  - Advancing the drug discovery and development process.
AB  - The current state of affairs in the drug discovery and development process is
      briefly summarized and then ways to take advantage of the ever-increasing
      fundamental knowledge and technical knowhow in chemistry and biology and related
      disciplines are discussed. The primary motivation of this Essay is to celebrate
      the great achievements of chemistry, biology, and medicine and to inform and
      inspire students and academics to enter the field of drug discovery and
      development while, at the same time, continue to advance the fundamentals of
      their disciplines. It is also meant to encourage and catalyze multidisciplinary
      partnerships between academia and industry as scientists attempt to merge their
      often complementary interests and expertise to achieve new improvements and
      breakthroughs in their respective fields, and the common goal of applying them to
      the discovery and invention of new and better medicines, especially in areas of
      unmet needs. 

PMID- 25045054
TI  - Physiological effects of temperature on turfgrass tolerance to amicarbazone.
AB  - BACKGROUND: Amicarbazone effectively controls annual bluegrass (Poa annua L.) in
      bermudagrass [Cynodon dactylon (L.) Pers. * C. transvaalensis Burtt-Davy] and
      tall fescue (Festuca arundinacea Schreb.) with spring applications, but summer
      applications may excessively injure tall fescue. The objective of this research
      was to investigate physiological effects of temperature on amicarbazone efficacy,
      absorption, translocation and metabolism in annual bluegrass, bermudagrass and
      tall fescue. RESULTS: At 25/20  degrees C (day/night), annual bluegrass absorbed
      58 and 40% more foliar-applied amicarbazone than bermudagrass and tall fescue,
      respectively, after 72 h. Foliar absorption increased at 40/35  degrees C in all
      species, compared with 25/20  degrees C, and tall fescue had similar absorption
      to annual bluegrass at 40/35  degrees C. At 6 days after treatment, annual
      bluegrass metabolized 54% of foliar-applied amicarbazone, while bermudagrass and
      tall fescue metabolized 67 and 64% respectively. CONCLUSION: Tall fescue is more
      tolerant to amicarbazone than annual bluegrass at moderate temperatures (~25/20 
      degrees C) owing to less absorption and greater metabolism. However, tall fescue
      susceptibility to amicarbazone injury at high temperatures (40/35  degrees C)
      results from enhanced herbicide absorption compared with lower temperatures
      (25/20  degrees C). Bermudagrass is more tolerant to amicarbazone than annual
      bluegrass and tall fescue owing to less herbicide absorption, regardless of
      temperature.

PMID- 25045055
TI  - Beta-blockers are associated with increased risk of first cardiovascular events
      in non-diabetic hypertensive elderly patients.
AB  - PURPOSE: Although treatment should be considered for elderly patients with
      hypertension (HTN), the effectiveness of beta-blockers (BBs) compared with other
      medications is less clear. This study's objective is to assess the relative
      effectiveness of BBs in elderly primary prevention patients with uncomplicated
      HTN. METHODS: This is a population-based nested case-control study. The cohort is
      composed of 94,844 elderly patients followed through 2009 and diagnosed with HTN
      between 2000 and 2004, without recent antecedents of diabetes, renal disease, or
      cardiovascular disease (CVD). Individuals with a CVD outcome were considered
      cases, and controls were matched to cases according to age, sex, date of cohort
      entry, and comorbidity index. Patients whose treatment included a BB were
      compared with patients on other HTN drug(s). RESULTS: The BB use by patients was
      associated with an increased risk for CVD events (odds ratio (OR) = 1.36, 95%CI:
      1.31-1.40) compared with patients using antihypertensive therapies without BBs.
      Sensitivity analyses suggest that this increased risk is not due to differences
      in prescription patterns on the basis of perceived disease severity. CONCLUSIONS:
      In real-world settings, antihypertensive therapies that include BBs are
      associated with less effective prevention of adverse outcomes in elderly
      hypertensive patients in primary prevention compared with antihypertensive
      therapies without BBs. Pending further studies, we recommend caution when
      prescribing BBs in primary prevention except when otherwise indicated.

PMID- 25045056
TI  - Pd/NbOPO4 multifunctional catalyst for the direct production of liquid alkanes
      from aldol adducts of furans.
AB  - Great efforts have been made to convert renewable biomass into transportation
      fuels. Herein, we report the novel properties of NbO(x)-based catalysts in the
      hydrodeoxygenation of furan-derived adducts to liquid alkanes. Excellent activity
      and stability were observed with almost no decrease in octane yield (>90%
      throughout) in a 256 h time-on-stream test. Experimental and theoretical studies
      showed that NbO(x) species play the key role in C-O bond cleavage. As a
      multifunctional catalyst, Pd/NbOPO4 plays three roles in the conversion of aldol
      adducts into alkanes: 1) The noble metal (in this case Pd) is the active center
      for hydrogenation; 2) NbO(x) species help to cleave the C-O bond, especially of
      the tetrahydrofuran ring; and 3) a niobium-based solid acid catalyzes the
      dehydration, thus enabling the quantitative conversion of furan-derived adducts
      into alkanes under mild conditions.

PMID- 25045057
TI  - Effect of extracellular vesicles of human adipose tissue on insulin signaling in
      liver and muscle cells.
AB  - OBJECTIVE: Insulin resistance (IR) is a key mechanism in obesity-induced
      cardiovascular disease. To unravel mechanisms whereby human adipose tissue (AT)
      contributes to systemic IR, the effect of human AT-extracellular vesicles (EVs)
      on insulin signaling in liver and muscle cells was determined. METHODS: EVs
      released from human subcutaneous (SAT) and omental AT (OAT)-explants ex vivo were
      used for stimulation of hepatocytes and myotubes in vitro. Subsequently, insulin
      induced Akt phosphorylation and expression of gluconeogenic genes (G6P, PEPCK)
      was determined. AT-EV adipokine levels were measured by multiplex immunoassay,
      and AT-EVs were quantified by high-resolution flow cytometry. RESULTS: In
      hepatocytes, AT-EVs from the majority of patients inhibited insulin-induced Akt
      phosphorylation, while EVs from some patients stimulated insulin-induced Akt
      phosphorylation. In myotubes AT-EVs exerted an ambiguous effect on insulin
      signaling. Hepatic Akt phosphorylation related negatively to G6P-expression by
      both SAT-EVs (r = -0.60, P = 0.01) and OAT-EVs (r = -0.74, P = 0.001). MCP-1, IL
      6, and MIF concentrations were higher in OAT-EVs compared to SAT-EVs and
      differently related to lower Akt phosphorylation in hepatocytes. Finally, the
      number of OAT-EVs correlated positively with liver enzymes indicative for liver
      dysfunction. CONCLUSIONS: Human AT-EVs can stimulate or inhibit insulin signaling
      in hepatocytes- possibly depending on their adipokine content- and may thereby
      contribute to systemic IR.

PMID- 25045058
TI  - The low risk of precancer after a screening result of human papillomavirus
      negative/atypical squamous cells of undetermined significance papanicolaou and
      implications for clinical management.
AB  - BACKGROUND: Different US practice guidelines have conflicting recommendations for
      when women should return after a screening result of human papillomavirus (HPV)
      negative with an equivocal Papanicolaou (Pap) result of atypical squamous cells
      of undetermined significance (ASC-US) (ie, return in either 3 or 5 years). One
      way to determine management is to compare the risk of precancer/cancer after an
      HPV-negative/ASC-US result with the risks after other negative screening results.
      For example, if the risk after an HPV-negative/ASC-US result was similar to the
      risk after a negative Pap test, a 3-year return would be preferred because
      guidelines agree that women with negative Pap test results should return in 3
      years. Alternatively, if the risk after an HPV-negative/ASC-US result is similar
      to that after a cotest-negative result (HPV negative/Pap test negative), a 5-year
      return would be preferred because guidelines agree that women testing cotest
      negative should return in 5 years. METHODS: The authors compared risks of
      cervical intraepithelial neoplasia of grade 3 or higher (CIN3+) and cervical
      cancer among women aged 30 years to 64 years at Kaiser Permanente Northern
      California with the following test results from 2003 through 2012: 17,191 women
      testing HPV negative/ASC-US; 980,268 women testing Pap test negative (regardless
      of HPV result); and 892,882 women testing cotest negative. RESULTS: The 5-year
      CIN3+ and cancer risks after an HPV-negative/ASC-US result were closer to the
      risks after a negative Pap test result (CIN3+: 0.48% vs 0.31% [P =.0019]; and
      cancer: 0.043% vs 0.031% [P =.4]) than after a negative cotest (CIN3+: 0.48% vs
      0.11% [P<.0001]; and cancer: 0.043% vs 0.014% [P =.016]). CONCLUSIONS: Women
      testing HPV negative/ASC-US were found to have precancer/cancer risks that were
      more closely aligned with women with negative Pap test results, suggesting that
      women testing HPV negative/ASC-US should be managed similarly to women testing
      negative on Pap tests with a 3-year return for screening.

PMID- 25045059
TI  - Prevention of orofacial clefts caused by smoking: implications of the Surgeon
      General's report.
AB  - BACKGROUND: According to the 2014 Surgeon General's Report, smoking in early
      pregnancy can cause orofacial clefts. We sought to examine the implications of
      this causal link for the potential prevention of orofacial clefts in the United
      States. METHODS: Using published data on the strength of the association between
      orofacial clefts and smoking in early pregnancy and the prevalence of smoking at
      the start of pregnancy, we estimated the attributable fraction for smoking as a
      cause of orofacial clefts. We then used the prevalence of orofacial clefts in the
      United States to estimate the number of orofacial clefts that could be prevented
      in the United States each year by eliminating exposure to smoking during early
      pregnancy. We also estimated the financial impact of preventing orofacial clefts
      caused by maternal smoking based on a published estimate of attributable
      healthcare costs through age 10 for orofacial clefts. RESULTS: The estimated
      attributable fraction of orofacial clefts caused by smoking in early pregnancy
      was 6.1% (95% uncertainty interval 4.4%, 7.7%). Complete elimination of smoking
      in early pregnancy could prevent orofacial clefts in approximately 430 infants
      per year in the United States, and could save an estimated $40.4 million in
      discounted healthcare costs through age 10 for each birth cohort. CONCLUSION:
      Understanding the magnitude of the preventable burden of orofacial clefts related
      to maternal smoking could help focus smoking cessation efforts on women who might
      become pregnant.

PMID- 25045060
TI  - Personalizing flow-diverter intervention for cerebral aneurysms: from
      computational hemodynamics to biochemical modeling.
AB  - This paper presents the computational modeling of a variety of flow-diverting
      stents, deployed in a number of patient-specific aneurysm geometries. We consider
      virtual device deployment and hemodynamics as well as thrombus formation, with
      the scope to assess pre-operatively the efficacy of specific devices in treating
      particular aneurysms. An algorithm based on a linear and torsional spring analogy
      is developed for the fast virtual deployment of stents and similar minimally
      invasive devices in patient-specific vessel geometries. The virtual deployment
      algorithm is used to accurately deploy a total of four stent designs in three
      aneurysm geometries. A variety of different flow-diverting stent designs,
      representing the commercially available and the entirely novel, are presented,
      varying in both mesh design and porosity. Transient computational hemodynamics
      simulations are performed on multiple patient-specific geometries to predict the
      reduction in aneurysm inflow after the deployment of each device. Further, a
      thrombosis initiation and growth model is implemented, coupled with the
      hemodynamic computations. Hemodynamic simulations show large variations in flow
      reduction between devices and across different aneurysm geometries. The industry
      standard of flow-diverters with 70% porosity, assumed to offer the best
      compromise in flexibility and flow reduction, is challenged in at least one
      aneurysm geometry.

PMID- 25045061
TI  - An osteosclerotic form of Robinow syndrome.
AB  - Robinow syndrome (RS) is a clinically and genetically heterogenous condition
      primarily characterized by short stature, mesomelia, genital hypoplasia, oral
      abnormalities, and a facial gestalt that includes hypertelorism, a short nose,
      and a broad mouth. The disorder exists in both a dominant and a more severe
      recessive form. Here two unrelated cases of sporadic RS are described with the
      additional finding of axial and appendicular osteosclerosis. These two patients,
      coupled with three additional patients previously described in the literature,
      may represent a distinct sub-phenotype of this condition.

PMID- 25045062
TI  - Preparation and characterization of bone marrow mesenchymal stem cell-derived
      extracellular matrix scaffolds.
AB  - The aim of this study was to assess the feasibility of creating extracellular
      matrix (ECM) scaffolds from mesenchymal stem cells. Bone marrow mesenchymal stem
      cell (BMSC)-derived ECM (BMSC-dECM) scaffolds were fabricated by lyophilization
      after crosslinking, without using a decellularization process. Acellular porcine
      chondrocyte-derived ECM (AC-dECM) scaffolds were used as a control. The surface
      morphology, internal structure, water uptake ratio, mechanical properties, and
      biocompatibility of the scaffolds, as well as the in vitro behavior of cells
      grown on the scaffolds were examined and compared between the two scaffold types.
      For the BMSC-dECM scaffolds, the average pore size was 304.4 +/- 108.2 MUm,
      average porosity was 93.3% +/- 4.5%, average compressive modulus was 6.8 +/- 1.5
      kPa, and average water uptake ratio exceeded 20. The BMSC-dECM scaffolds
      supported the in vitro attachment and proliferation of cells, with these aspects
      likely being comparable to those of the AC-dECM scaffolds. The findings of this
      preliminary study highlight the potential utility of BMSC-derived ECM scaffolds
      for future cartilage tissue-engineering applications.

PMID- 25045064
TI  - Plasmonic nanorattles with intrinsic electromagnetic hot-spots for surface
      enhanced Raman scattering.
AB  - The synthesis of plasmonic nanorattles with accessible electromagnetic hotspots
      that facilitate highly sensitive detection of chemical analytes using surface
      enhanced Raman scattering (SERS) is demonstrated. Raman spectra obtained from
      individual nanorattles demonstrate the significantly higher SERS activity
      compared to solid plasmonic nanostructures. 

PMID- 25045063
TI  - Role of semaphorin-1a in the developing visual system of the disease vector
      mosquito Aedes aegypti.
AB  - BACKGROUND: Despite the devastating impact of mosquito-borne illnesses on human
      health, very little is known about mosquito developmental biology, including
      development of the mosquito visual system. Mosquitoes possess functional adult
      compound eyes as larvae, a trait that makes them an interesting model in which to
      study comparative developmental genetics. Here, we functionally characterize
      visual system development in the dengue and yellow fever vector mosquito Aedes
      aegypti, in which we use chitosan/siRNA nanoparticles to target the axon guidance
      gene semaphorin-1a (sema1a). RESULTS: Immunohistochemical analyses revealed the
      progression of visual sensory neuron targeting that results in generation of the
      retinotopic map in the mosquito optic lobe. Loss of sema1a function led to optic
      lobe phenotypes, including defective targeting of visual sensory neurons and
      failed formation of the retinotopic map. These sema1a knockdown phenotypes
      correlated with behavioral defects in larval photoavoidance. CONCLUSIONS: The
      results of this investigation indicate that Sema1a is required for optic lobe
      development in A. aegypti and highlight the behavioral importance of a
      functioning visual system in preadult mosquitoes.

PMID- 25045065
TI  - Functional correlates of cognitive dysfunction in multiple sclerosis: A
      multicenter fMRI Study.
AB  - In this multicenter study, we applied functional magnetic resonance imaging
      (fMRI) to define the functional correlates of cognitive dysfunction in patients
      with multiple sclerosis (MS). fMRI scans during the performance of the N-back
      task were acquired from 42 right-handed relapsing remitting (RR) MS patients and
      52 sex-matched right-handed healthy controls, studied at six European sites using
      3.0 Tesla scanners. Patients with at least two abnormal (<2 standard deviations
      from the normative values) neuropsychological tests at a standardized evaluation
      were considered cognitively impaired (CI). FMRI data were analyzed using the SPM8
      software, modeling regions showing load-dependent activations/deactivations with
      increasing task difficulty. Twenty (47%) MS patients were CI. During the N-back
      load condition, compared to controls and CI patients, cognitively preserved (CP)
      patients had increased recruitment of the right dorsolateral prefrontal cortex.
      As a function of increasing task difficulty, CI MS patients had reduced
      activations of several areas located in the fronto-parieto-temporal lobes as well
      as reduced deactivations of regions which are part of the default mode network
      compared to the other two groups. Significant correlations were found between
      abnormal fMRI patterns of activations and deactivations and behavioral measures,
      cognitive performance, and brain T2 and T1 lesion volumes. This multicenter study
      supports the theory that a preserved fMRI activity of the frontal lobe is
      associated with a better cognitive profile in MS patients. It also indicates the
      feasibility of fMRI to monitor disease evolution and treatment effects in future
      studies.

PMID- 25045066
TI  - Peak purity assessment in a triple-active fixed-dose combination drug product
      related substances method using a commercial two-dimensional liquid
      chromatography system.
AB  - Pharmaceutical formulations containing multiple active components challenge the
      development of analytical methods, especially as the individual active
      ingredients diverge in their physicochemical properties. Establishing
      specificity, especially peak purity, is one of the major evaluation criteria when
      developing a related substances method for drug substances or products. Fixed
      dose combination products may not be amenable to common strategies for assessing
      peak purity, such as performing orthogonal separations, due to the complexity of
      the separation and/or diversity of the active ingredients. An alternate approach
      to evaluating peak purity is demonstrated for a triple-active component fixed
      dose combination product under development. A commercially available automated
      two-dimensional liquid chromatography system was used to perform a selective
      comprehensive multidimensional separation of an active ingredient peak. The first
      dimension performed the drug product impurity/degradant profiling method; the
      second dimension assayed these fractions using the drug substance profiling
      method, which was pseudo-orthogonal to the first dimension. A total of 14
      targeted fractions were sampled across the first dimension main peak, with 11
      containing detectable analytes and the remaining fractions bracketing the main
      peak. This degree of sampling allowed profiling of a coeluting degradant present
      at a 0.2% w/w level throughout the main peak. 

PMID- 25045067
TI  - Expression of ganglioside 9-O acetyl GD3 in undifferentiated embryonic stem
      cells.
AB  - Embryonic stem cells (ES cells) express a transient and heterogeneous pattern of
      molecules, which suggests a notable mechanism to control self-renewal avoid the
      differentiation into germ layers. We show that 9-O-acetyl GD3 (9OacGD3), a highly
      expressed b-series ganglioside in neural stem (NS) cells, is expressed in
      undifferentiated mouse ES cells in a heterogeneous fashion. After sorting,
      undifferentiated 9OacGD3(+) ES cell population had higher levels of nestin and
      Sox2 mRNA than the 9OacGD3(-) cells. Even with elevated expression of these
      neural transcription factors, 9OacGD3(+) cells did not give rise to more neural
      progenitors than 9OacGD3(-) cells. Expression of 9OacGD3 was recovered from
      9OacGD3(-) cell population, demonstrating that expression of this ganglioside in
      mouse embryonic stem cells is transient, and does not reflect cell fate. Our
      findings show that the ganglioside 9OacGD3 is expressed heterogeneously and
      transiently in ES cells, and this expression corresponds to higher levels of Sox2
      and Nestin transcripts. 

PMID- 25045068
TI  - Efficacy of a small cell-binding peptide coated hydroxyapatite substitute on bone
      formation and implant fixation in sheep.
AB  - Cylindrical critical size defects were created at the distal femoral condyles
      bilaterally of eight female adult sheep. Titanium implants with 2-mm concentric
      gaps were inserted and the gaps were filled with one of the four materials:
      allograft; a synthetic 15-amino acid cell-binding peptide coated hydroxyapatite
      (ABM/P-15); hydroxyapatite + betatricalciumphosphate+ Poly-Lactic-Acid
      (HA/betaTCP-PDLLA); or ABM/P-15+HA/betaTCP-PDLLA. After nine weeks, bone-implant
      blocks were harvested and sectioned for micro-CT scanning, push-out test, and
      histomorphometry. Significant bone formation and implant fixation could be
      observed in all four groups. Interestingly, the microarchitecture of the ABM/P-15
      group was significantly different from the control group. Tissue volume fraction
      and thickness were significantly greater in the ABM/P-15 group than in the
      allograft group. Bone formation and bone ingrowth to porous titanium implant were
      not significantly different among the four groups. The ABM/P-15 group had similar
      shear mechanical properties on implant fixation as the allograft group. Adding
      HA/betaTCP-PDLLA to ABM/P-15 did not significantly change these parameters. This
      study revealed that ABM/P-15 had significantly bone formation in concentric gap,
      and its enhancements on bone formation and implant fixation were at least as good
      as allograft. It is suggested that ABM/P-15 might be a good alternative
      biomaterial for bone implant fixation in this well-validated critical-size defect
      gap model in sheep. Nevertheless, future clinical researches should focus on
      prospective, randomized, controlled trials in order to fully elucidate whether
      ABM/P-15 could be a feasible candidate for bone substitute material in orthopedic
      practices.

PMID- 25045069
TI  - A multifunctional nanomicelle for real-time targeted imaging and precise near
      infrared cancer therapy.
AB  - Simultaneous targeted cancer imaging, therapy and real-time therapeutic
      monitoring can prevent over- or undertreatment. This work describes the design of
      a multifunctional nanomicelle for recognition and precise near-infrared (NIR)
      cancer therapy. The nanomicelle encapsulates a new pH-activatable fluorescent
      probe and a robust NIR photosensitizer, R16FP, and is functionalized with a newly
      screened cancer-specific aptamer for targeting viable cancer cells. The
      fluorescent probe can light up the lysosomes for real-time imaging. Upon NIR
      irradiation, R16FP-mediated generation of reactive oxygen species causes
      lysosomal destruction and subsequently trigger lysosomal cell death. Meanwhile
      the fluorescent probe can reflect the cellular status and in situ visualize the
      treatment process. This protocol can provide molecular information for precise
      therapy and therapeutic monitoring. 

PMID- 25045070
TI  - Hybrid polyglycerols with long blood circulation: synthesis, biocompatibility,
      and biodistribution.
AB  - Multifunctional polymers with defined structure and biocompatibility are critical
      to the development of drug delivery systems and bioconjugates. In this article,
      the synthesis, in vitro blood compatibility, cell viability, in vivo circulation,
      biodistribution, and clearance of hybrid copolymers based on linear and branched
      polyglycerol are reported. Hybrid polyglycerols (M(n) ~ 100 kDa) are synthesized
      with different compositions (15-80 mol% linear polyglycerol). Relatively small
      hydrodynamic size and radius of gyration of the hybrid polyglycerols suggest that
      they are highly compact functional nanostructures. The hybrid polyglycerols show
      excellent blood compatibility as determined by measuring their effects on blood
      coagulation, red blood cell aggregation, hemolysis, platelet, and complement
      activation. The cell viability in presence of hybrid polyglycerols is excellent
      up to 10 mg mL(-1) concentration and is similar to both dextran and polyvinyl
      alcohol. Furthermore, tritium labeled hybrid polyglycerol shows long blood
      circulation (t(1/2beta)= 34 h) with minimal organ accumulation in mice.
      Multifunctionality, compact nature, biocompatibility, and the long blood
      circulation make these polymers attractive for the development of bioconjugates
      and drug delivery systems.

PMID- 25045071
TI  - Delineating definitions and risk factors for metabolic syndrome after pediatric
      liver transplantation.

PMID- 25045072
TI  - Synthesis of (+/-)-tetrapetalone A-Me aglycon.
AB  - The first synthesis of (+/-)-tetrapetalone A-Me aglycon is described. Key bond
      forming reactions include Nazarov cyclization, a ring-closing metathesis promoted
      with complete diastereoselectivity by a chiral molybdenum-based complex, tandem
      conjugate reduction/intramolecular aldol cyclization, and oxidative
      dearomatization. 

PMID- 25045073
TI  - The impact of cyclopropane configuration on the biological activity of
      cyclopropyl-epothilones.
AB  - Two cis-12,13-cyclopropyl-epothilone B variants have been synthesized, differing
      only in the configuration of the stereocenters at C12 and C13. The syntheses were
      based on a common allylic alcohol intermediate that was converted into the
      corresponding diastereomeric hydroxymethyl-cyclopropanes by means of
      stereoselective Charette cyclopropanations. Macrocyclizations were accomplished
      through ring-closing metathesis (RCM). Substantial differences between the two
      compounds were found with regard to microtubule binding affinity,
      antiproliferative activity and their effects on the cellular microtubule network.
      While the analogue with the cyclopropane moiety oriented in a corresponding way
      to the epoxide configuration in natural epothilones was almost equipotent with
      epothilone A, the other was significantly less active. Based on these findings,
      natural epothilone-like activity of cis-fused 12,13-cyclopropyl-epothilone
      analogues is tightly linked to the natural orientation of the cyclopropane
      moiety. 

PMID- 25045074
TI  - Protein interactions with polymer coatings and biomaterials.
AB  - Protein adsorption is considered to be the most important factor of the
      interaction between polymeric biomaterials and body fluids or tissues. Water
      mediated hydrophobic and hydration forces as well as electrostatic interactions
      are believed to be the major factors of protein adsorption. A systematic analysis
      of various monolayer systems has resulted in general guidelines, the so-called
      "Whitesides rules". These concepts have been successfully applied for designing
      various protein-resistant surfaces and are being studied to expand the
      understanding of protein-material interactions beyond existing limitations.
      Theories on the mechanisms of protein adsorption are constantly being improved
      due to the fast-developing analytical technologies. This Review is aimed at
      improving these empirical guidelines with regard to present theoretical and
      analytical advances. Current analytical methods to test mechanistic hypotheses
      and theories of protein-surface interactions will be discussed. Special focus
      will be given to state-of-the-art bioinert and biospecific coatings and their
      applications in biomedicine. 

PMID- 25045075
TI  - Review of MRI positioning devices for guiding focused ultrasound systems.
AB  - BACKGROUND: This article contains a review of positioning devices that are
      currently used in the area of magnetic resonance imaging (MRI) guided focused
      ultrasound surgery (MRgFUS). METHODS: The paper includes an extensive review of
      literature published since the first prototype system was invented in 1991.
      RESULTS: The technology has grown into a fast developing area with application to
      any organ accessible to ultrasound. The initial design operated using hydraulic
      principles, while the latest technology incorporates piezoelectric motors.
      Although, in the beginning there were fears regarding MRI safety, during recent
      years, the deployment of MR-safe positioning devices in FUS has become routine.
      Many of these positioning devices are now undergoing testing in clinical trials.
      CONCLUSION: Existing MRgFUS systems have been utilized mostly in oncology
      (fibroids, brain, liver, kidney, bone, pancreas, eye, thyroid, and prostate). It
      is anticipated that, in the near future, there will be a positioning device for
      every organ that is accessible by focused ultrasound.

PMID- 25045077
TI  - Spotlights on our sister journals: ChemBioChem 11/2014.

PMID- 25045078
TI  - Sleep pathology characterization in sickle cell disease: case-control study.
AB  - BACKGROUND: Children and adolescents with sickle cell disease (SCD) have a higher
      incidence of sleep pathology and obstructive sleep apnea syndrome (OSAS). The
      nocturnal hypoxemia is a risk to vaso-occlusive crisis among other SCD
      morbidities. Our aim was to compare polysomnography (PSG) results in a sample of
      children with SCD with a sample of children with suspected OSAS without SCD.
      DESIGN AND METHODS: A retrospective study compared clinical and PSG parameters. A
      descriptive analysis and t-test were done considering P < 0.05 as significant.
      RESULTS: PSG was done in 65 children with SCD and 65 control-children. Control
      sample was selected to be equal to SCD sample considering gender (53.8% were
      male), age (mean age was 9.4 years (SD +/- 4.6) and AHI (mean 3.57 events/hr).
      Mean efficiency, latency and percentage of sleep phases in both groups showed no
      statistically significant differences. Mean SpO2 and minimum SpO2 were lower in
      SCD group and it was statistically significant (P < 0.01). Enuresis was more
      frequent in the SCD children group (35.4% vs. 6.2%, P < 0.01). CONCLUSION:
      Comparing children with and without SCD, sleep architecture was similar in both
      groups and minimum SpO2 was significantly lower in SCD children although both
      groups had a similar AHI. This is an important issue in these children, so it is
      essential to have a sleep evaluation in order to prevent complications and co
      morbidities.

PMID- 25045079
TI  - Hollow-fiber liquid-phase microextraction for the direct determination of
      flumequine in urban wastewaters by flow-injection analysis with terbium
      sensitized chemiluminescence.
AB  - A flow-injection analysis chemiluminescence method based on the enhancement
      effect of the flumequine-Tb(III) complex on the weak native emission of the
      Ce(IV)-Na2SO3 system has been developed for the determination of flumequine. The
      method includes a cleanup and preconcentration stage (750-fold) of the sample by
      hollow-fiber liquid-phase microextraction using an Accurel((r)) Q 3/2
      polypropylene hollow fiber impregnated with 1-octanol as the supported liquid
      membrane. The obtained 50 MUL acceptor phase was injected in a 1 mM Tb(III) + 4
      mM Ce(IV) in 5% v/v H2 SO4 stream and mixed with a 2 mM Na2 SO3 stream before its
      introduction into the flow cell. The chemiluminescence signal was linear in the
      0.3-15 ng/mL range, with detection and quantitation limits of 0.1 and 0.3 ng/mL,
      respectively. The method allows the selective extraction and determination of
      flumequine in wastewater samples, using simpler and lower-cost instrumentation
      and with shorter extraction and analysis times than traditional high-performance
      liquid chromatography analysis.

PMID- 25045080
TI  - Genetic variants in BRIP1 (BACH1) contribute to risk of nonsyndromic cleft lip
      with or without cleft palate.
AB  - BACKGROUND: The etiology of nonsyndromic cleft lip with or without cleft palate
      (NSCL/P) is very complex and still not well elucidated. Given the critical role
      of DNA damage repair in the embryonic development, we decided to test the
      hypothesis that polymorphisms of selected DNA repair genes might contribute to
      the risk of NSCL/P in the Polish population. METHODS: Analysis of 36
      polymorphisms in 12 DNA damage repair genes (ATM, BLM, BRCA1, BRIP1, E2F1, MLH1,
      MRE11A, MSH2, MSH6, NBN, RAD50, and RAD51) was conducted using TaqMan assays in a
      group of 263 NSCL/P patients and matched control group (n = 526). RESULTS:
      Statistical analysis of genotyping results revealed that nucleotide variants in
      the BRIP1 (BACH1) gene were associated with the risk of NSCL/P. Under assumption
      of a dominant model, the calculated odds ratios (ORs) for BRIP1 rs8075370 and
      rs9897121 were 1.689 (95% confidence interval [CI], 1.249-2.282; p = 0.0006) and
      1.621 (95% CI, 1.200-2.191; p = 0.0016), respectively. These results were
      statistically significant even after applying multiple testing correction.
      Additional evidence for a causative role of BRIP1 in NSCL/P etiology was provided
      by haplotype analysis. Borderline association with a decreased risk of this
      anomaly was also observed for BLM rs401549 (ORrecessive = 0.406; 95% CI, 0.223
      1.739; p = 0.002) and E2F1 rs2071054 (ORdominant = 0.632; 95% CI, 0.469-0.852; p
      = 0.003). CONCLUSION: Our study suggests that polymorphic variants of DNA damage
      repair genes play a role in the susceptibility to NSCL/P. BRIP1 might be novel
      candidate gene for this common developmental anomaly.

PMID- 25045081
TI  - Effects of epigallocatechin-3-gallate on the healing of extraction sockets with a
      periapical lesion: A pilot study in dogs.
AB  - The aim of this study was to characterize the healing process of extraction
      sockets with a periapical lesion following immediate graft with collagenated
      bovine bone mineral (CBBM) soaked with epigallocatechin-3-gallate (EGCG).
      Following induction of periapical lesions in premolars in five dogs, treatment of
      extraction sockets was divided into three groups: control (no treatment) and two
      test groups, CBBM with or without EGCG. 3D reconstruction and superimposition of
      the digital images were used to measure the dimensional changes in alveolar
      ridge. Histologic specimen was evaluated in all groups. The horizontal ridge
      widths at 4-mm level were wider in both test groups (3.3 +/- 1.7 mm in CBBM; 3.0
      +/- 1.7 mm in CBBM+EGCG) than in the control group (1.7 +/- 2.4 mm). Fibrosis and
      limited new bone formation were observed in the apical regions of test groups;
      however, the extent of fibrosis was less in the CBBM+EGCG group. Within the
      limitations of this study, it was conjectured that adjunctive use of EGCG with
      CBBM can be a candidate biomaterial in grafting of extraction socket with
      periapical lesion. Bone regeneration at the coronal region of the CBBM grafted
      socket might not be influenced by the presence of a periapical lesion.

PMID- 25045082
TI  - Validity of the dipole approximation in TEM-EELS studies.
AB  - Nondipole effects in electron energy-loss spectroscopy are evaluated in terms of
      deviation of the inelastic scattering from a Lorentzian angular distribution,
      which is assumed in established procedures for plural-scattering deconvolution,
      thickness measurement, and Kramers-Kronig analysis. The deviation appears to be
      small and may be outweighed by the effect of plural (elastic + inelastic)
      scattering, which is not removed by conventional deconvolution methods. In the
      core-loss region of the spectrum, non-Lorentzian behaviour stems from a reduction
      of the generalized oscillator strength from its optical value and (for energies
      far above an ionization threshold) formation of a Bethe-ridge angular
      distribution. At incident energies above 200 keV, retardation effects further
      distort the angular dependence, even for core losses just above threshold. With
      an on-axis collection aperture, non-dipole effects are masked by the rapid
      falloff of intensity with scattering angle, but they may become important for off
      axis measurements. Near-edge fine structure is sensitive to nondipole effects but
      these can be minimized by use of an angle-limiting collection aperture.

PMID- 25045083
TI  - Interatrial differences of basal molecular set-up and changes in tachycardia
      induced heart failure-a proteomic profiling study.
AB  - AIMS: Left and right atria show compelling differences regarding organogenesis
      and specific clinical diseases. In congestive heart failure (CHF), remodelling of
      the atria occurs leading to increased arrhythmogenic susceptibility and
      deterioration of clinical symptoms. We aimed to assess the basal left and right
      atrial molecular set-up and different chamber-specific atrial changes in heart
      failure. METHODS AND RESULTS: We combined an animal model of rapid ventricular
      pacing induced heart failure in the rabbit and a gel-based proteomic screening of
      left and right atrial specimen. A gene ontology over-representation analysis was
      performed for biological function. Ultrastructural adaptations were evaluated
      using transmission electron microscopy. Comparing left and right atria of healthy
      control animals (CTRL), 39 proteins displayed significant expression differences
      involving various biological functions. Upon further statistical analyses, four
      pathways of energy metabolism were confirmed to be significantly over-represented
      beneath the other biological processes. Rapid ventricular pacing induced severe
      left ventricular systolic dysfunction, symptomatic heart failure and a
      macroscopic atrial remodelling. In CHF versus CTRL, metabolic and antioxidative
      enzymes were differentially expressed and showed chamber-specific bidirectional
      alterations. Transmission electron microscopy visualized a remarkable and again
      chamber-specific ultrastructural disturbance of mitochondrial morphology.
      CONCLUSIONS: Our data indicate a diverging basal left and right atrial molecular
      set-up in the adult healthy heart. In addition, metabolic and antioxidative
      enzymes are profoundly and chamber-specifically altered during atrial remodelling
      in progressive heart failure.

PMID- 25045086
TI  - Temporal and spatial aspects of experimental tonic pain: Understanding pain
      adaptation and intensification.
AB  - BACKGROUND: The underlying mechanisms of adaptations to pain are unclear. In
      order to explore whether central or peripheral mechanisms predominate, the
      effects of two centrally mediated phenomena - spatial summation of pain (SSP) and
      transcutaneous electrical nerve stimulation (TENS) - were examined. The effect of
      the degree of painfulness, rather than absolute stimulation intensity, was also
      examined. METHODS: Seventeen participants received several series of individually
      adjusted tonic noxious-heat stimuli (300 s), inducing an initial perceived pain
      of 2 (mild pain), 4 (moderate pain) and 6 (strong pain) on a visual analogue
      scale (VAS). The stimuli were administered to small (2.25 cm2) and large (9 cm2)
      areas to produce SSP and also during TENS treatment, during which 12 VAS ratings
      were obtained. RESULTS: Adaptation occurred during VAS-2 stimulation and was
      minimal, followed by intensification during VAS-4 stimulation, whereas VAS-6
      stimulation always induced pain intensification. TENS failed to produce analgesia
      and SSP did not affect adaptation but affected intensification. Stimulation
      temperatures affected the magnitude of adaptation and intensification within each
      degree of painfulness. The mathematical models that best fitted the time trend
      with VAS-2 and VAS-4 were linear, whereas a power function best fitted VAS-6
      stimulation. CONCLUSIONS: The mathematical models and the lack of effect of SSP
      on adaptation suggest that its dominant component is peripheral. Whereas relative
      painfulness determines whether pain adaptation or intensification occurs
      (probably a defence mechanism), absolute stimulation intensities influence the
      magnitude of the effect. Pain intensification is differentially affected by probe
      size, depending upon the occurrence of initial adaptation.

PMID- 25045084
TI  - Precise spatial coding is preserved along the longitudinal hippocampal axis.
AB  - Compared with the dorsal hippocampus, relatively few studies have characterized
      neuronal responses in the ventral hippocampus. In particular, it is unclear
      whether and how cells in the ventral region represent space and/or respond to
      contextual changes. We recorded from dorsal and ventral CA1 neurons in freely
      moving mice exposed to manipulations of visuospatial and olfactory contexts. We
      found that ventral cells respond to alterations of the visuospatial environment
      such as exposure to novel local cues, cue rotations, and contextual expansion in
      similar ways to dorsal cells, with the exception of cue rotations. Furthermore,
      we found that ventral cells responded to odors much more strongly than dorsal
      cells, particularly to odors of high valence. Similar to earlier studies
      recording from the ventral hippocampus in CA3, we also found increased scaling of
      place cell field size along the longitudinal hippocampal axis. Although the
      increase in place field size observed toward the ventral pole has previously been
      taken to suggest a decrease in spatial information coded by ventral place cells,
      we hypothesized that a change in spatial scaling could instead signal a shift in
      representational coding that preserves the resolution of spatial information. To
      explore this possibility, we examined population activity using principal
      component analysis (PCA) and neural location reconstruction techniques. Our
      results suggest that ventral populations encode a distributed representation of
      space, and that the resolution of spatial information at the population level is
      comparable to that of dorsal populations of similar size. Finally, through the
      use of neural network modeling, we suggest that the redundancy in spatial
      representation along the longitudinal hippocampal axis may allow the hippocampus
      to overcome the conflict between memory interference and generalization inherent
      in neural network memory. Our results indicate that ventral population activity
      is well suited for generalization across locations and contexts.

PMID- 25045085
TI  - Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid
      adenocarcinoma cell line.
AB  - Cancer-initiating cells (CICs) are a limited number of cells that are essential
      for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1
      (ALDH1) has been recognized as a marker of CICs. We previously reported that
      ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis,
      and that ALDH1 high population was more tumorigenic, invasive, and resistant to
      apoptosis than ALDH1 low population. Histamine plays a critical role in cancer
      cell proliferation, migration, and invasion. Here, we examined the effect of
      histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The
      addition of histamine increased ALDH1 high population, which was consistent with
      the result that histamine enhanced the invasive ability and the resistance to
      anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2
      receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line.
      The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist
      H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These
      results indicated that histamine increased the expression of ALDH1 via H1R but
      not H2R. These findings may provide the evidence for exploring a new strategy to
      suppress CICs by inhibiting ALDH1 expression with histamine. 

PMID- 25045087
TI  - Novel Na(+) doped Alq3 hybrid materials for organic light-emitting diode (OLED)
      devices and flat panel displays.
AB  - Pure and Na(+) -doped Alq3 complexes were synthesized by a simple precipitation
      method at room temperature, maintaining a stoichiometric ratio. These complexes
      were characterized by X-ray diffraction, Fourier transform infrared (FTIR),
      UV/Vis absorption and photoluminescence (PL) spectra. The X-ray diffractogram
      exhibits well-resolved peaks, revealing the crystalline nature of the synthesized
      complexes, FTIR confirms the molecular structure and the completion of quinoline
      ring formation in the metal complex. UV/Vis absorption and PL spectra of sodium
      doped Alq3 complexes exhibit high emission intensity in comparison with Alq3
      phosphor, proving that when doped in Alq3 , Na(+) enhances PL emission intensity.
      The excitation spectra of the synthesized complexes lie in the range 242-457 nm
      when weak shoulders are also considered. Because the sharp excitation peak falls
      in the blue region of visible radiation, the complexes can be employed for blue
      chip excitation. The emission wavelength of all the synthesized complexes lies in
      the bluish green/green region ranging between 485 and 531 nm. The intensity of
      the emission wavelength was found to be elevated when Na(+) is doped into Alq3 .
      Because both the excitation and emission wavelengths fall in the visible region
      of electromagnetic radiation, these phosphors can also be employed to improve the
      power conversion efficiency of photovoltaic cells by using the solar spectral
      conversion principle. Thus, the synthesized phosphors can be used as bluish
      green/green light-emitting phosphors for organic light-emitting diodes, flat
      panel displays, solid-state lighting technology - a step towards the desire to
      reduce energy consumption and generate pollution free light.

PMID- 25045088
TI  - Osmotic regulation and tissue localization of the myo-inositol biosynthesis
      pathway in tilapia (Oreochromis mossambicus) larvae.
AB  - The myo-inositol biosynthesis (MIB) pathway converts glucose-6-phosphate to the
      compatible osmolyte myo-inositol, which protects cells from salinity stress. We
      exposed tilapia larvae just after yolk sac resorption to various hypersaline
      environments and recorded robust induction of the enzymes that constitute the MIB
      pathway, myo-inositol-phosphate synthase (MIPS), and inositol monophosphatase 1
      (IMPA1). Strong up-regulation of these enzymes is evident at both mRNA
      (quantitative real-time PCR) and protein (densitometric analysis of Western
      blots) levels. The highest level of induction of these enzymes occurs at the
      highest salinity that larvae were exposed to (90 ppt). Less severe salinity
      stress causes a proportionately reduced induction of the MIB pathway. Two
      distinct MIPS mRNA variants are present in tilapia larvae and both are induced at
      comparable levels for all the salinity challenges tested (34, 70, and 90 ppt).
      Immunohistochemical localization of IMPA1 protein in sagittal sections of
      salinity stressed and control larvae identified tissues that are particularly
      potent in inducing the MIB pathway. These tissues include the skin (epidermis),
      gills, eye (ciliary epithelium) and heart. In particular, the epidermis directly
      facing the external milieu showed a very strong induction of IMPA1
      immunoreactivity. IMPA1 induction in response to salinity stress was not observed
      in other tissues suggesting that tilapia larvae may also utilize compatible
      organic osmolytes other than solely myo-inositol for osmoprotection. We conclude
      that the MIB pathway plays an important role in protecting multiple (but not all)
      tissues of tilapia larvae from hyperosmotic salinity stress.

PMID- 25045089
TI  - Theoretical study on experimentally detected Sc2S@C84.
AB  - Sc(2)S@C(84) has recently been detected but not structurally characterized.1
      Density functional theory calculations on C(84) and Sc(2)S@C(84) show that the
      favored isomer of Sc(2)S@C84 shares the same parent cage as Sc(2)C2@C(84),
      whereas Sc(2)S@C(84):51383, which violates the isolated-pentagon rule, is the
      second lowest energy isomer with the widest HOMO-LUMO gap and shows high kinetic
      stability. The analysis shows that Sc(2)S@C(84):51575 is favored when the
      temperature exceeds 2,800 K and it can transform into the most favorable isomer
      Sc(2)S@C(84):51591. Molecular orbital analysis indicates that both Sc(2)S and
      Sc(2)C(2) formally transfer four electrons to the cage, and quantum theory of
      atoms in molecules analysis demonstrates that there is a covalent interaction
      between Sc(2)S and C(84):51591. The IR spectra of Sc(2)S@C(84) are provided to
      aid future structural identification.

PMID- 25045090
TI  - SCAI/ACC/AHA Expert Consensus Document: 2014 Update on Percutaneous Coronary
      Intervention Without On-Site Surgical Backup.

PMID- 25045091
TI  - Have we found the optimal solution for "Swiss cheese" ASDs yet?

PMID- 25045092
TI  - Do not rock the BOAT: the latest atherectomy device improvement trial.

PMID- 25045093
TI  - Renal function and carotid artery disease: many questions, few answers.

PMID- 25045094
TI  - This usually goes much better than this.

PMID- 25045095
TI  - Small annulus or small patient? It's the aortic complex that matters for TAVR.

PMID- 25045096
TI  - Management of the low-ejection fraction patient with aortic stenosis.

PMID- 25045097
TI  - Realizing the percutaneous dream: postprocedure benefits of optimizing minimally
      invasive technique.

PMID- 25045098
TI  - The impact of left anterior descending coronary artery length on survival
      following myocardial infarction: to the apex and beyond.

PMID- 25045099
TI  - Drug-coated balloon after coronary stenting falls short.

PMID- 25045100
TI  - Wire externalization versus "rendez-vous" for successfully completing retrograde
      chronic total occlusion interventions.

PMID- 25045102
TI  - Two trihydrazine-bridged cobalt(II) chain compounds exhibiting antiferromagnetic
      ordering and single-chain magnetic behavior.
AB  - Two new trihydrazine bridged Co(II) chain compounds have been synthesized and
      magnetically characterized. The two compounds are both composed of
      [Co(N2H4)3](2+) chains. One exhibits antiferromagnetic ordering behavior while
      the other behaves as a single-chain magnet (SCM) at low temperature.

PMID- 25045103
TI  - Mode of action analysis for pesticide-induced rodent liver tumours involving
      activation of the constitutive androstane receptor: relevance to human cancer
      risk.
AB  - A number of non-genotoxic chemicals, including some pesticides, have been shown
      to increase the incidence of liver tumours in rats and/or mice. Frameworks for
      analysing the modes of action (MOAs) by which chemicals produce liver tumours in
      rodents and the relevance of such tumour data for human risk assessment have now
      been established. One common MOA for rodent liver tumour formation by non
      genotoxic chemicals involves activation of the constitutive androstane receptor
      (CAR). Key and associative events for a CAR-activation MOA include receptor
      activation, liver hypertrophy, induction of cytochrome P450 enzyme activities,
      increased replicative DNA synthesis, altered hepatic foci and liver tumours.
      While some effects of rodent CAR activators can be observed in human liver, a
      major species difference is that, unlike rodents, CAR activators do not increase
      replicative DNA synthesis in human hepatocytes. The CAR-activation MOA for rodent
      liver tumour formation is thus not plausible for humans, and hence such compounds
      do not pose a hepatocarcinogenic hazard for humans.

PMID- 25045104
TI  - Biological production of muconic acid via a prokaryotic 2,3-dihydroxybenzoic acid
      decarboxylase.
AB  - Non-oxidative decarboxylases belong to a unique enzyme family that does not
      require any cofactors. Here we report the characterization of a 2,3
      dihydroxybenzoic acid (2,3-DHBA) decarboxylase (BDC) from Klebsiella pneumoniae
      and explore its application on the production of muconic acid. The enzyme
      properties were systematically studied, including the optimal temperature and pH,
      kinetic parameters, and substrate specificity. On this basis, we designed an
      artificial pathway for muconic acid production by connecting 2,3-DHBA
      biosynthesis with its degradation pathway. Over-expression of entCBA and the key
      enzymes in the shikimate pathway led to the production of 900 mg L(-1) of 2,3
      DHBA. Further, expression of the BDC coupled with catechol 1,2-dioxygenase
      achieved the conversion of 2,3-DHBA into muconic acid. Finally, assembly of the
      total pathway resulted in the de novo production of muconic acid up to 480 mg L(
      1).

PMID- 25045105
TI  - Psychosocial interventions addressing the needs of Black women diagnosed with
      breast cancer: a review of the current landscape.
AB  - BACKGROUND: Poorer health outcomes and lower survival rates have been well
      documented among African American/Black (Black) women diagnosed with breast
      cancer. Black women are 41% more likely to die from breast cancer than White
      women despite a lower incidence rate. Apart from pharmacotherapy, psychosocial
      interventions are recommended by the Institute of Medicine as standard medical
      care for breast cancer patients at all phases of treatment. The current review is
      the first attempt to systematically evaluate the literature on the influence of
      psychosocial interventions for Black women diagnosed with breast cancer. METHODS:
      This systematic review aimed to adhere to the Preferred Reporting Items for
      Systematic Reviews and Meta-analyses guidelines. A comprehensive computerized
      literature search of CINAHL, PsycINFO, PubMed, and Web of Science was conducted
      to obtain relevant studies. RESULTS: Interventions demonstrated improved mood,
      decreased distress, increased ability to cope with intrusive thoughts and cancer
      related stress, personal growth, and improved social well-being. However, aspects
      unique to this population require additional scientific inquiry. Over 80% of
      empirical interventions focused on Black women diagnosed with breast cancer have
      been concentrated on the posttreatment phase. There is a paucity of work at the
      time of diagnosis and during treatment. CONCLUSIONS: To address gaps in the
      scientific literature, more work is needed to better understand how psychosocial
      interventions can improve the health trajectory for Black women diagnosed with
      breast cancer particularly in the areas of seeking help and support, identifying
      culturally acceptable methods for engaging support networks, and identifying best
      practices for enhancing coping skills.

PMID- 25045106
TI  - A novel nonpharmacologic technique to remove entrapped radial sheath.
AB  - Radial artery access for performance of coronary and peripheral diagnostic as
      well as interventional procedures is on the rise. With increasing adoption comes
      the expected increase in procedural complications. We describe a novel, simple,
      and effective nonpharmacologic solution for sheath entrapment related to pharmaco
      resistant radial artery spasm. (c) 2014 Wiley Periodicals, Inc. 

PMID- 25045107
TI  - T-CrAsH: a heterologous chemical crosslinker.
AB  - Copper-free click chemistry is currently the most promising and most rapidly
      developing technology for performing tailored chemical reactions inside intact
      living cells and animals. Its potential is particularly intensely explored in the
      field of live cell imaging, for both proteins and metabolites. Here we expand the
      application spectrum of click reactions to the chemical crosslinking of two
      proteins of choice in living cells. By combining strain-promoted Diels-Alder
      cycloaddition with FlAsH-based labeling of peptidic tetracysteine motifs, we
      developed the membrane-permeating reversible crosslinker T-CrAsH. We demonstrate
      the feasibility of the method both in vitro and inside cells. The biggest
      advantage of this new tool is the small size of the crosslinkable groups; this
      significantly decreases the risk of functional interference. 

PMID- 25045108
TI  - Endless: a purine-binding RNA motif that can be expressed in cells.
AB  - It is becoming increasingly clear that nature uses RNAs extensively for
      regulating vital functions of the cell, and short sequences are frequently used
      to suppress gene expression. However, controlling the concentration of small
      molecules intracellularly through designed RNA sequences that fold into ligand
      binding structures is difficult. The development of "endless", a triplex-based
      folding motif that can be expressed in mammalian cells and binds the second
      messenger 3',5'-cyclic guanosine monophosphate (cGMP), is described. In vitro,
      DNA or RNA versions of endless show low micromolar to nanomolar dissociation
      constants for cGMP. To test its functionality in vivo, four endless RNA motifs
      arranged in tandem were co-expressed with a fluorescent cGMP sensor protein in
      murine vascular smooth muscle cells. Nitric oxide induced endogenous cGMP signals
      were suppressed in endless-expressing cells compared to cells expressing a
      control motif, which suggests that endless can act as a genetically encoded cGMP
      sink to modulate signal transduction in cells. 

PMID- 25045109
TI  - Light-driven organocatalysis using inexpensive, nontoxic Bi2O3 as the
      photocatalyst.
AB  - The development of enantioselective catalytic processes that make use of sunlight
      as the energy source and nontoxic, affordable materials as catalysts represents
      one of the new and rapidly evolving areas in chemical research. The direct
      asymmetric alpha-alkylation of aldehydes with alpha-bromocarbonyl compounds can
      be successfully achieved by combining bismuth-based materials as low-band-gap
      photocatalysts with the second-generation MacMillan imidazolidinone as the chiral
      catalyst and simulated sunlight as a low-cost and clean energy source. This
      reaction also proceeded with high efficiency when the reaction vial was exposed
      to the morning sunlight on a clear September day in Tarragona, Spain. 

PMID- 25045110
TI  - Enantioselective formation of cyano-bearing all-carbon quaternary stereocenters:
      desymmetrization by copper-catalyzed N-arylation.
AB  - The enantioselective construction of all-carbon quaternary stereocenters is one
      of the most challenging fields in asymmetric synthesis. An asymmetric
      desymmetrization strategy offers an indirect and efficient method for the
      formation of all-carbon stereocenters. An enantioselective formation of cyano
      bearing all-carbon quaternary stereocenters in 1,2,3,4,-tetrahydroquinolines and
      2,3,4,5-tetrahydro-1H-benzo[b]azepines by copper-catalyzed desymmetric N
      arylation is demonstrated. The cyano group at the prochiral center plays a key
      role for the high enantioselectivity and works as an important functional group
      for further transformations. DFT studies provide a model which successfully
      accounts for the origin of enantioselectivity. 

PMID- 25045112
TI  - Effect of preparation method and CuO promotion in the conversion of ethanol into
      1,3-butadiene over SiO2-MgO catalysts.
AB  - Silica-magnesia (Si/Mg=1:1) catalysts were studied in the one-pot conversion of
      ethanol to butadiene. The catalyst synthesis method was found to greatly
      influence morphology and performance, with materials prepared through wet
      kneading performing best both in terms of ethanol conversion and butadiene yield.
      Detailed characterization of the catalysts synthesized through co-precipitation
      or wet-kneading allowed correlation of activity and selectivity with morphology,
      textural properties, crystallinity, and acidity/basicity. The higher yields
      achieved with the wet-kneaded catalysts were attributed to a morphology
      consisting of SiO2 spheres embedded in a thin layer of MgO. The particle size of
      the SiO2 catalysts also influenced performance, with catalysts with smaller SiO2
      spheres showing higher activity. Temperature-programmed desorption (TPD)
      measurements showed that best butadiene yields were obtained with SiO2-MgO
      catalysts characterized by an intermediate amount of acidic and basic sites. A
      Hammett indicator study showed the catalysts' pK(a) value to be inversely
      correlated with the amount of dehydration by-products formed. Butadiene yields
      could be further improved by the addition of 1 wt% of CuO as promoter to give
      butadiene yields and selectivities as high as 40% and 53%, respectively. The
      copper promoter boosts the production of the acetaldehyde intermediate changing
      the rate-determining step of the process. TEM-energy-dispersive X-ray (EDX)
      analyses showed CuO to be present on both the SiO2 and MgO components. UV/Vis
      spectra of promoted catalysts in turn pointed at the presence of cluster-like CuO
      species, which are proposed to be responsible for the increased butadiene
      production.

PMID- 25045111
TI  - Pharmacokinetics of prenylated hop phenols in women following oral administration
      of a standardized extract of hops.
AB  - SCOPE: Women seeking alternatives to hormone-replacement therapy for menopausal
      symptoms often try botanical dietary supplements containing extracts of hops
      (Humulus lupulus L.). Hops contain 8-prenylnaringenin (8-PN), a potent
      phytoestrogen, the related flavanones 6-prenylnaringenin and isoxanthohumol (IX),
      and the prenylated chalcone xanthohumol (XN). METHODS AND RESULTS: After
      chemically and biologically standardizing an extract of spent hops to these
      marker compounds, an escalating dose study was carried out in menopausal women to
      evaluate safety and pharmacokinetics. 8-PN, 6-prenylnaringenin, IX, and XN, sex
      hormones, and prothrombin time were determined in blood samples and/or 24 h urine
      samples. There was no effect on sex hormones or blood clotting. The maximum serum
      concentrations of the prenylated phenols were dose-dependent and were reached
      from 2 to 7 h, indicating slow absorption. The marker compounds formed
      glucuronides that were found in serum and urine. Secondary peaks at 5 h in the
      serum concentration-time curves indicated enterohepatic recirculation. The serum
      concentration-time curves indicated demethylation of IX to form 8-PN and
      cyclization of XN to IX. Slow absorption and enterohepatic recirculation
      contributed to half-lives exceeding 20 h. CONCLUSION: This human study indicated
      long half-lives of the estrogenic and proestrogenic prenylated phenols in hops
      but no acute toxicity.

PMID- 25045113
TI  - Core-shell structure of hierarchical quasi-hollow MoS2 microspheres encapsulated
      porous carbon as stable anode for Li-ion batteries.
AB  - Monodisperse sulfonated polystyrene (SPS) microspheres are employed as both the
      template and carbon source to prepare MoS2 quasi-hollow microspheres-encapsulated
      porous carbon. The synthesis procedure involves the hydrothermal growth of MoS2
      ultrathin nanosheets on the surface of SPS microspheres and subsequent annealing
      to remove SPS core. Incomplete decomposition of SPS during annealing due to the
      confining effect of MoS2 shells leaves residual porous carbon in the interior.
      When being evaluated as the anode materials of Li-ion batteries, the as-prepared
      C@MoS2 microspheres exhibit excellent cycling stability (95% of capacity retained
      after 100 cycles) and high rate behavior (560 mAh g(-1) at 5 A g(-1)).

PMID- 25045114
TI  - Acid-base-responsive intense charge-transfer emission in donor-acceptor
      conjugated fluorophores.
AB  - Herein we report on the synthesis and acid-responsive emission properties of
      donor-acceptor (D-A) molecules that contain a thienothiophene unit. 2
      Arylthieno[3,2-b]thiophenes were conjugated with an N-methylbenzimidazole unit to
      form acid-responsive D-A-type fluorophores. The D-A-conjugated fluorophores
      showed intense intramolecular charge-transfer (ICT) emission in response to acid.
      The effect of the substitution on their photophysical properties as well as their
      solvent-dependence indicated non-twisting ICT emission in protonated D-A
      molecules. The quinoidal character of 2-arylthienothiophene as a donor part is
      discussed, as it is assumed that it contributes to suppression of the molecular
      twisting in the excited state, therefore decreasing the nonradiative rate
      constant, thereby resulting in the intense ICT emission. Acid-base-sensitive
      triple-color emission was also achieved by the introduction of a base-responsive
      phenol group in the donor part. 

PMID- 25045115
TI  - The biomechanical effects of stapes replacement by prostheses on the tympano
      ossicular chain.
AB  - Hearing is a sequence of processes in which the ear translates sound waves into
      electrical signals, which are then sent to the brain where they are interpreted
      as sound. The ossicular chain of the middle ear is formed by three ossicles
      (malleus, incus, and stapes), of which the last and smallest, the stapes,
      vibrates, thus communicating with the inner ear through the stapes footplate.
      When abnormal bone formation immobilizes the stapes (otosclerosis), the passage
      of sound does not correctly occur and hearing can be compromised. In most cases,
      surgery is an option for its treatment. The stapes is totally or partially
      replaced by a prosthesis (stapedectomy or stapedotomy, respectively) allowing the
      passage of sound to the inner ear. This work presents a study on the behavior of
      different stapes prostheses, considering their biomechanical characteristics. The
      stapes was replaced by different prostheses, made of dissimilar materials:
      stainless steel, teflon, and titanium. The umbo and stapes footplate
      displacements for the models with these prostheses were obtained and compared
      with the displacements obtained with the model representative of the normal ear.
      In the models with prostheses, the displacements are found in the hole where the
      prosthesis is attached.

PMID- 25045116
TI  - Lung cancer adrenal gland metastasis: Optimal fine-needle aspirate and touch
      preparation smear cellularity characteristics for successful theranostic next
      generation sequencing.
AB  - BACKGROUND: Multigene molecular testing to guide personalized therapy for
      oncology patients is of increasing clinical relevance. Molecular testing of fine
      needle aspiration samples is underused, but when acquired with minimally invasive
      techniques could become the standard of care to obtain theranostic specimens. The
      aims of the current study were to identify key cytology specimen selection
      criteria suitable for next-generation sequencing (NGS) and to determine the
      prevalence and spectrum of pathogenic alterations in a cohort of patients with
      AJCC stage IV lung cancer. METHODS: A total of 70 adrenal gland cytology
      specimens with direct smears were screened to identify 56 patients with a single
      slide containing at least 300 total cells and 20% tumor nuclei. After DNA
      extraction, the NGS protocols were used to simultaneously detect mutations in
      >2800 exonic regions in 50 key cancer genes. RESULTS: A total of 28 specimens
      produced acceptable NGS results. Specimens with a combined critical cell mass
      (>5000 viable cells) and a DNA concentration >5 ng/uL resulted in a 95% chance of
      successful sequencing. A total of 37 pathogenic alterations were identified in 10
      genes and in 25 patients (85%). A pathogenic alteration (>=1) linked to available
      or developing targeted therapies was revealed in 50% of cases. CONCLUSIONS: The
      data from the current study demonstrate that theranostic NGS can be applied to
      adrenal gland metastasis using routine cytologic smear specimens. The
      characteristics of such smears could be evaluated during onsite adequacy
      assessment by cytopathology professionals. This model greatly augments the
      opportunity for customized genotype-directed therapy from minimally invasive
      techniques.

PMID- 25045117
TI  - A conical intersection controls the deactivation of the bacterial luciferase
      fluorophore.
AB  - The photophysics of flavins is highly dependent on their environment. For
      example, 4a-hydroxy flavins display weak fluorescence in solution, but exhibit
      strong fluorescence when bound to a protein. To understand this behavior, we
      performed temperature-dependent fluorescent studies on an N(5)-alkylated 4a
      hydroxy flavin: the putative bacterial luciferase fluorophore. We find an
      increase in fluorescence quantum yield upon reaching the glass transition
      temperature of the solvent. We then employ multiconfigurational quantum chemical
      methods to map the excited-state deactivation path of the system. The result
      reveals a shallow but barrierless excited state deactivation path that leads to a
      conical intersection displaying an orthogonal out-of-plane distortion of the
      terminal pyrimidine ring. The intersection structure readily explains the
      observed spectroscopic behavior in terms of an excited-state barrier imposed by
      the rigid glass cavity. 

PMID- 25045118
TI  - Synthesis of bridged oxafenestranes from pleuromutilin.
AB  - Fenestranes are an intriguing class of highly strained molecules possessing a
      quaternary carbon with bonds that deviate from the canonical tetrahedral
      geometry. Herein we report the discovery that the natural product pleuromutilin
      can be used as a structurally complex starting material for the synthesis of a
      series of bridged cis,cis,cis,cis-[4.5.5.5]- and cis,cis,cis,cis
      [4.5.7.5]oxafenestranes through a carbocation rearrangement cascade. X-ray
      crystallographic analysis of several cis,cis,cis,cis-[4.5.5.5]oxafenestranes
      shows a significant planarization of the central tetracoordinate carbon atom and
      demonstrates the influence of bridgehead substituents and bridging rings on
      planarity. 

PMID- 25045119
TI  - Involvement of L-type Ca2+ channel and toll-like receptor-4 in nickel-induced
      interleukin-8 gene expression.
AB  - The metal nickel (Ni(2+)) is found everywhere in our daily lives, including
      coins, costume jewelry, and even nuts and chocolates. Nickel poisoning can cause
      inflammatory reactions, respiratory diseases, and allergic contact dermatitis. To
      clarify the mechanism by which nickel induces mediators of inflammation, we used
      the human acute monocytic leukemia THP-1 cell line as a model. Interleukin (IL)-8
      promoter activity as well as gene expression were tested by luciferase assay and
      real-time polymerase chain reaction. The underlying mechanisms of nickel-induced
      IL-8 were investigated. We found that nickel induced IL-8 gene expression via the
      L-type Ca(2+) channel, Toll-like receptor-4 (TRL-4) and nuclear factor NF-kappaB
      signal transduction pathways. Nickel activated NF-kappaB expression through
      extracellular signal-regulated kinase 1/2 phosphorylation and then increased IL-8
      expression. Thus, the L-type Ca(2+) channel and TRL-4 play important roles in
      nickel-induced inflammatory gene expressions.

PMID- 25045120
TI  - Asthma-like symptoms as a presentation of antiphospholipid syndrome.
AB  - We herein report a case of antiphospholipid syndrome (APS) primarily presenting
      with asthma-like symptoms that had been misdiagnosed as severe asthma. Patients
      presenting with severe asthma symptoms along with systemic thrombosis should be
      systematically evaluated for APS.

PMID- 25045121
TI  - Highly sensitive fluorescence and SERS detection of azide through a simple click
      reaction of 8-chloroquinoline and phenylacetylene.
AB  - In 0.19 mol/L acetic acid (HAc), a click reaction of 8
      chloroquinoline/azide/phenylacetylene take places in aqueous solution without
      Cu(I) as a catalyst. 8-Chloroquinoline (CQN) exhibited a strong fluorescence peak
      at 430 nm that was quenched linearly as the concentration of azide increased from
      20 to 1000 ng/mL. This quenching was due to consumption of CQN in the click
      reaction and a decrease in the number of efficiently excited photons due to the
      presence of triazole-quinoline ramification molecules with strong hydrophobicity.
      Using blue nanosilver sol as the substrate, CQN absorbed onto the surface of
      nanosilver particles, showing a strong surface-enhanced Raman scattering (SERS)
      peak at 1585 cm(-1) that decreased linearly as the azide concentration increased
      from 8 to 500 ng/mL; the detection limit was 4 ng/mL. Thus, two new, simple and
      sensitive fluorescence and SERS methods have been developed for the determination
      of azide via the click reaction.

PMID- 25045122
TI  - Ketanserin, a serotonin 2A receptor antagonist, alleviates ischemia-related
      biliary fibrosis following donation after cardiac death liver transplantation in
      rats.
AB  - Biliary fibrosis is a major complication after donation after cardiac death (DCD)
      liver transplantation. In this process, the roles of serotonin [5
      hydroxytryptamine (5-HT)] and the 5-HT2A receptor subtype are still unknown. In
      this study, we analyzed markers of portal fibroblast (PF)/myofibroblast (MF)
      transdifferentiation such as transforming growth factor beta1 (TGF-beta1),
      phosphorylated smad2/3, alpha-smooth muscle actin (alpha-SMA), collagen I, and
      collagen III in a primary culture system of PFs after the administration of 5-HT
      or 5-HT plus ketanserin (a selective 5-HT2A receptor antagonist). A rat DCD
      transplant model was established with 30 minutes of warm ischemia and 4 hours of
      cold ischemia during organ procurement. Recipients were intraperitoneally
      injected with ketanserin (1 mg.kg(-1).day(-1)) or normal saline. Grafts without
      in situ warm ischemia instead of minimal cold storage (30 minutes) served as
      controls. The serum biochemistry, the liver contents of 5-HT and hydroxyproline
      (HYP), and the expression of fibrosis-related genes (including TGF-beta1, matrix
      metalloproteinase 2, procollagen alpha1, and alpha-SMA messenger RNA) were
      determined. The extent of biliary fibrosis was also assessed histopathologically.
      The results indicated that ketanserin inhibited 5-HT-activated TGF-beta1-smad2/3
      signaling in vitro and thereby depressed the MF conversion of PFs. Rats receiving
      DCD livers showed increased liver contents of 5-HT and HYP, impaired biliary
      function, up-regulation of fibrosis-related genes, and aggravated biliary
      fibrosis. However, these phenomena were alleviated by treatment with ketanserin.
      We concluded that the profibrotic activity of 5-HT occurred through the
      activation of TGF-beta1 signaling and the 5-HT2A receptor. Thus, these data
      suggest that the 5-HT2A receptor may be a potential therapeutic target for
      ischemia-related biliary fibrosis after DCD liver transplantation.

PMID- 25045123
TI  - The biocatalytic repertoire of natural biaryl formation.
AB  - The catalytic and selective construction of carbon-carbon bonds for the
      generation of complex molecules is one of the most important tasks in organic
      chemistry. This was clearly highlighted by the 2010 Nobel Prize in Chemistry,
      which was awarded for the development of Pd-catalyzed cross-coupling reactions.
      The underlying concept of cross-linking building blocks to generate molecular
      complexity can also be widely found in natural product biosynthesis. Impressive
      examples for such natural cross-coupling reactions are biosynthetic processes for
      the assembly of biaryl moieties in natural products--highly efficient enzymatic
      reactions that often achieve synthetically yet unmatched selectivities. This
      Minireview highlights selected examples that showcase these fascinating
      biotransformations.

PMID- 25045124
TI  - Leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 genes expression by mitogen
      activated protein kinases and NF-KB signaling pathways in human chondrocytes.
AB  - Elucidation of the causes of inflammation has vital importance in the development
      of new approaches for the treatment of arthritic diseases. The degradation of
      aggrecan by upregulated disintegrin and metalloproteinase with trombospondin
      motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis
      (RA) and osteoarthritis (OA). Increased levels of leptin in both RA and OA have
      been demonstrated, thus linking leptin to arthritic diseases, but the mechanism
      has not been clarified. This study investigated the putative role of signaling
      pathways (p38, JNK, MEK1, NF-KB, and PI3) involved in leptin-induced cartilage
      destruction. Normal human articular chondrocytes were cultured with recombinant
      human leptin at 100, 250, 500, and 1000 ng/mL doses for 6, 12, 24, and 48 h,
      after which ADAMTS-4, -5, and -9 genes expression were determined by real time
      polymerase chain reaction (RT-PCR) and Western Blot methods. The signaling
      pathways involved in leptin-induced ADAMTSs upregulation were also investigated
      by using inhibitors of signaling pathways. It was demonstrated that ADAMTSs
      expression level was peaked at 1000 ng/mL doses for 48 hours, and MAPKs (p38,
      JNK, and MEK) and NF-KB signaling pathways involving in leptin triggered ADAMTSs
      upregulation. Obesity as a risk for RA and OA may contribute to the inflammation
      of both RA and OA diseases by secreting adipokines like leptin. We hypothesize
      that leptin is involved in the development of RA and OA accompanied with obesity
      by increasing ADAMTS-4, -5, and -9 genes expression via MAPKs and NF-KB signaling
      pathways.

PMID- 25045125
TI  - Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease.
AB  - Parkinson's disease (PD) is an age-related neurodegenerative disease affecting
      movement. To date, there are no currently available therapeutic agents which can
      prevent or slow disease progression. Here, we evaluated an azobenzene derivative,
      methyl yellow (MY), as a potential drug scaffold for PD; its inhibitory activity
      toward monoamine oxidase B (MAO-B) as well as drug-like properties were
      investigated. The inhibitory effect of MY on MAO activity was determined by a MAO
      enzyme inhibition assay. In addition, the in vitro properties of MY as a drug
      candidate (e.g., blood-brain barrier (BBB) permeability, serum albumin binding,
      drug efflux through P-glycoprotein (P-gp), drug metabolism by P450, and
      mitochondrial toxicity) were examined. In vivo effectiveness of MY was also
      evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian
      mouse model. MY selectively inhibited MAO-B in a dose-dependent and reversible
      manner. MY was BBB-permeable, bound relatively weakly to serum albumin, was an
      unlikely substrate for both systems of P-gp and P450, and did not cause
      mitochondrial toxicity. Results from the MPTP Parkinsonian mouse model indicated
      that, upon treatment with MY, neurotoxicity induced by MPTP was mitigated.
      Investigations of MY demonstrate its inhibitory activity toward MAO-B, compliant
      properties for drug consideration, and its neuroprotective capability in the MPTP
      Parkinsonian mouse model. These data provide insights into potential use,
      optimization, and new design of azobenzene derivatives for PD treatment.

PMID- 25045126
TI  - DNA nanostructure-based imaging probes and drug carriers.
AB  - Self-assembled DNA nanostructures are well-defined nanoscale shapes, with uniform
      sizes, precise spatial addressability, and excellent biocompatibility. With these
      features, DNA nanostructures show great potential for biomedical applications;
      various DNA-based biomedical imaging probes or payload delivery carriers have
      been developed. In this review, we summarize the recent developments of DNA-based
      nanostructures as tools for diagnosis and cancer therapy. The biological effects
      that are brought about by DNA nanostructures are highlighted by in vitro and in
      vivo imaging, antitumor drug delivery, and immunostimulatory therapy. The
      challenges and perspectives of DNA nanostructures in the field of nanomedicine
      are discussed. 

PMID- 25045127
TI  - Frequency-dependent neural activity in Parkinson's disease.
AB  - The brainstem and basal ganglia are important in the pathophysiology of
      Parkinson's disease (PD). Reliable and sensitive detection of neural activity
      changes in these regions should be helpful in scientific and clinical research on
      PD. In this study, we used resting state functional MRI and amplitude of low
      frequency fluctuation (ALFF) methods to examine spontaneous neural activity in
      109 patients with PD. We examined activity in two frequency bands, slow-4
      (between 0.027 and 0.073 Hz) and slow-5 (0.010-0.027 Hz). Patients had decreased
      ALFF in the striatum and increased ALFF in the midbrain, and changes were more
      significant in slow-4. Additionally, changes in slow-4 in both basal ganglia and
      midbrain correlated with the severity of the parkinsonism. The ALFF in the
      caudate nucleus positively correlated with the dose of levodopa, while the ALFF
      in the putamen negatively correlated with the disease duration in both slow-4 and
      slow-5 bands. In addition, the ALFF in the rostral supplementary motor area
      negatively correlated with bradykinesia subscale scores. Our findings show that
      with a large cohort of patients and distinguishing frequency bands, neural
      modulations in the brainstem and striatum in PD can be detected and may have
      clinical relevance. The physiological interpretation of these changes needs to be
      determined.

PMID- 25045129
TI  - Thermal acclimation and nutritional history affect the oxidation of different
      classes of exogenous nutrients in Siberian hamsters, Phodopus sungorus.
AB  - During acclimatization to winter, changes in morphology and physiology combined
      with changes in diet may affect how animals use the nutrients they ingest. To
      study (a) how thermal acclimation and (b) nutritional history affect the rates at
      which Siberian hamsters (Phodopus sungorus) oxidize different classes of dietary
      nutrients, we conducted two trials in which we fed hamsters one of three (13) C
      labeled compounds, that is, glucose, leucine, or palmitic acid. We predicted that
      under acute cold stress (3 hr at 2 degrees C) hamsters previously acclimated to
      cold temperatures (10 degrees C) for 3 weeks would have higher resting metabolic
      rate (RMR) and would oxidize a greater proportion of dietary fatty acids than
      animals acclimated to 21 degrees C. We also investigated how chronic nutritional
      stress affects how hamsters use dietary nutrients. To examine this, hamsters were
      fed four different diets (control, low protein, low lipid, and low-glycemic
      index) for 2 weeks. During cold challenges, hamsters previously acclimated to
      cold exhibited higher thermal conductance and RMR, and also oxidized more
      exogenous palmitic acid during the postprandial phase than animals acclimated to
      21 degrees C. In the nutritional stress trial, hamsters fed the low protein diet
      oxidized more exogenous glucose, but not more exogenous palmitic acid than the
      control group. The use of (13) C-labeled metabolic tracers combined with breath
      testing demonstrated that both thermal and nutritional history results in
      significant changes in the extent to which animals oxidize dietary nutrients
      during the postprandial period.

PMID- 25045128
TI  - Whole exome sequencing identifies three novel mutations in ANTXR1 in families
      with GAPO syndrome.
AB  - GAPO syndrome (OMIM#230740) is the acronym for growth retardation, alopecia,
      pseudoanodontia, and optic atrophy. About 35 cases have been reported, making it
      among one of the rarest recessive conditions. Distinctive craniofacial features
      including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high
      forehead, mid-facial hypoplasia, hypertelorism, and thickened eyelids and lips
      make GAPO syndrome a clinically recognizable phenotype. While this genomic study
      was in progress mutations in ANTXR1 were reported to cause GAPO syndrome. In our
      study we performed whole exome sequencing (WES) for five affected individuals
      from three Turkish kindreds segregating the GAPO trait. Exome sequencing analysis
      identified three novel homozygous mutations including; one frame-shift
      (c.1220_1221insT; p.Ala408Cysfs*2), one splice site (c.411A>G; p.Gln137Gln), and
      one non-synonymous (c.1150G>A; p.Gly384Ser) mutation in the ANTXR1 gene. Our
      studies expand the allelic spectrum in this rare condition and potentially
      provide insight into the role of ANTXR1 in the regulation of the extracellular
      matrix.

PMID- 25045130
TI  - Determination of bisphenol A, 4-octylphenol, and 4-nonylphenol in soft drinks and
      dairy products by ultrasound-assisted dispersive liquid-liquid microextraction
      combined with derivatization and high-performance liquid chromatography with
      fluorescence detection.
AB  - A novel hyphenated method based on ultrasound-assisted dispersive liquid-liquid
      microextraction coupled to precolumn derivatization has been established for the
      simultaneous determination of bisphenol A, 4-octylphenol, and 4-nonylphenol by
      high-performance liquid chromatography with fluorescence detection. Different
      parameters that influence microextraction and derivatization have been optimized.
      The quantitative linear range of analytes is 5.0-400.0 ng/L, and the correlation
      coefficients are more than 0.9998. Limits of detection for soft drinks and dairy
      products have been obtained in the range of 0.5-1.2 ng/kg and 0.01-0.04 MUg/kg,
      respectively. Relative standard deviations of intra- and inter-day precision for
      retention time and peak area are in the range of 0.47-2.31 and 2.76-8.79%,
      respectively. Accuracy is satisfactory in the range of 81.5-118.7%. Relative
      standard deviations of repeatability are in the range of 0.35-1.43 and 2.36-4.75%
      for retention time and peak area, respectively. Enrichment factors for bisphenol
      A, 4-octylphenol, and 4-nonylphenol are 170.5, 240.3, and 283.2, respectively.
      The results of recovery and matrix effect are in the range of 82.7-114.9 and 92.0
      109.0%, respectively. The proposed method has been applied to the determination
      of bisphenol A, 4-octylphenol, and 4-nonylphenol in soft drinks and dairy
      products with much higher sensitivity than many other methods. 

PMID- 25045131
TI  - SrO- and MgO-doped microwave sintered 3D printed tricalcium phosphate scaffolds:
      mechanical properties and in vivo osteogenesis in a rabbit model.
AB  - The presence of interconnected macro pores allows guided tissue regeneration in
      tissue engineering scaffolds. However, highly porous scaffolds suffer from having
      poor mechanical strength. Previously, we showed that microwave sintering could
      successfully be used to improve mechanical strength of macro porous tricalcium
      phosphate (TCP) scaffolds. This study reports the presence of SrO and MgO as
      dopants in TCP scaffolds improves mechanical and in vivo biological performance.
      We have used direct three dimensional printing (3DP) technology for scaffold
      fabrication. These 3DP scaffolds possessed multiscale porosity, that is, 3D
      interconnected designed macro pores along with intrinsic micro pores. A
      significant increase in mechanical strength, between 37 and 41%, was achieved due
      to SrO and MgO doping in TCP as compared with pure TCP. Maximum compressive
      strengths of 9.38 +/- 1.86 MPa and 12.01 +/- 1.56 MPa were achieved by
      conventional and microwave sintering, respectively, for SrO-MgO-doped 3DP
      scaffolds with 500 MUm designed pores. Histomorphological and histomorphometric
      analysis revealed a significantly higher osteoid, bone and haversian canal
      formation induced by the presence of SrO and MgO dopants in 3DP TCP as compared
      with pure TCP scaffolds when tested in rabbit femoral condyle defect model.
      Increased osteon and thus enhanced network of blood vessel formation, and
      osteocalcin expression were observed in the doped TCP scaffolds. Our results show
      that these 3DP SrO-MgO-doped TCP scaffolds have the potential for early wound
      healing through accelerated osteogenesis and vasculogenesis.

PMID- 25045134
TI  - C-THV measures of self-expandable valve positioning and correlation with implant
      outcomes.
AB  - BACKGROUND: Accurate positioning of the valve device during transcutaneous aortic
      valve implantation (TAVI) is of crucial importance. The Paieon C-THV navigation
      system has been designed to correctly guide device deployment during TAVI.
      OBJECTIVES: Using this navigation system we aimed to determine the correlation
      between the anatomic measures of the native aortic valve and the deployed self
      expandable valve positioning and to explore the impact upon procedural outcomes.
      METHODS: We analyzed data of 68 patients with severe symptomatic aortic stenosis
      undergoing TAVI, using the catheter-based Medtronic-CoreValve self-expandable
      system. Patients were subdivided into two groups according to whether the C-THV
      system was used (50) or not (18) during the implantation process. Analysis of
      geometrical outcomes vs. clinical outcomes including postprocedural electrical
      conduction defect and/or para-valvular leaks was performed. RESULTS: Taking the
      target implantation line as a reference; relatively lower vs. higher
      implantations correlated with a higher frequency of any new onset electrical
      conduction defect (ECD). The mean corresponding distance from valve inferior edge
      below the virtual aortic annulus line was 3.0 +/- 1.6 mm vs. 1.2 +/- 1.3 mm in
      patients with (38.5%) vs. without any new onset ECD, respectively (P = 0.05). The
      use of C-THV navigation seemed to correlate with higher valve implants but it had
      no impact on the occurrence of postprocedural paravalvular leaks. CONCLUSIONS:
      Self-expandable valve implants guided by C-THV navigation seems to be associated
      with more precise implants and lower risk for postprocedural electrical
      conduction defects, due to higher location in relation to the target line.

PMID- 25045133
TI  - Catalytic enantioselective carboannulation with allylsilanes.
AB  - The first catalytic asymmetric carboannulation with allylsilanes is presented.
      The enantioselective [3+2] annulation is catalyzed using a
      scandium(III)/indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]
      borate (BArF) to enhance catalytic activity and control stereoselectivity.
      Functionalized cyclopentanes containing a quaternary carbon center are derived
      from alkylidene oxindole, coumarin, and malonate substrates with high
      stereoselectivity. The enantioselective 1,4-conjugate addition and
      enantioselective lactone formation (by trapping of the beta-silyl carbocation) is
      also described. 

PMID- 25045132
TI  - Bioorthogonal fluorescent labeling of functional G-protein-coupled receptors.
AB  - Novel methods are required for site-specific, quantitative fluorescent labeling
      of G-protein-coupled receptors (GPCRs) and other difficult-to-express membrane
      proteins. Ideally, fluorescent probes should perturb the native structure and
      function as little as possible. We evaluated bioorthogonal reactions to label
      genetically encoded p-acetyl-L-phenylalanine (AcF) or p-azido-L-phenylalanine
      (azF) residues in receptors heterologously expressed in mammalian cells. We found
      that keto-selective reagents were not truly bioorthogonal, possibly owing to post
      translational protein oxidation reactions. In contrast, the strain-promoted [3+2]
      azide-alkyne cycloaddition (SpAAC) with dibenzocyclooctyne (DIBO) reagents
      yielded stoichiometric conjugates with azF-rhodopsin while undergoing negligible
      background reactions. As one application of this technique, we used Alexa488
      rhodopsin to measure the kinetics of ligand uptake and release in membrane
      mimetic bicelles using a novel fluorescence-quenching assay. 

PMID- 25045135
TI  - Lung function over the first 3 years of life in children with congenital
      diaphragmatic hernia.
AB  - OBJECTIVES: Infants with congenital diaphragmatic hernia (CDH) have variable
      degrees of pulmonary hypoplasia at birth. Few reports of lung function over the
      first years of life exist in this group of children. HYPOTHESIS: Pulmonary
      function abnormalities correlate with severity of neonatal disease and intensity
      of neonatal therapies needed. We also hypothesized that longitudinal measurements
      of lung function over the usual period of rapid lung growth would lend some
      insight into how the lung remodels in CDH infants. METHODOLOGY: Ninety-eight
      infants with CDH between 11 days and 44 months of age underwent pulmonary
      function testing (PFT) on 1-5 occasions using the raised volume rapid thoracic
      compression technique. Demographic data were also collected. MAIN RESULTS: Forced
      expiratory flows were below normal. Total lung capacity was normal, but residual
      volume and functional residual capacity were elevated. Children requiring patch
      closure, ECMO, or pulmonary vasodilators generally had lower lung functions at
      follow up. Additionally, longer duration of mechanical ventilation correlated
      with worse lung function. CONCLUSIONS: Lung functions of survivors of CDH remain
      abnormal throughout the first 3 years of life. The degree of pulmonary function
      impairment correlated both with markers of the initial degree of pulmonary
      hypoplasia and the duration of mechanical ventilation. Understanding the
      relationship between the phenotypic presentation of CDH and the potential for
      subsequent lung growth could help refine both pre- and postnatal therapies to
      optimize lung growth in CDH infants.

PMID- 25045136
TI  - Energy upconversion in GaP/GaNP core/shell nanowires for enhanced near-infrared
      light harvesting.
AB  - Semiconductor nanowires (NWs) have recently gained increasing interest due to
      their great potential for photovoltaics. A novel material system based on GaNP
      NWs is considered to be highly suitable for applications in efficient multi
      junction and intermediate band solar cells. This work shows that though the
      bandgap energies of GaN(x)P(1-x) alloys lie within the visible spectral range
      (i.e., within 540-650 nm for the currently achievable x < 3%), coaxial GaNP NWs
      grown on Si substrates can also harvest infrared light utilizing energy
      upconversion. This energy upconversion can be monitored via anti-Stokes near-band
      edge photoluminescence (PL) from GaNP, visible even from a single NW. The
      dominant process responsible for this effect is identified as being due to two
      step two-photon absorption (TS-TPA) via a deep level lying at about 1.28 eV above
      the valence band, based on the measured dependences of the anti-Stokes PL on
      excitation power and wavelength. The formation of the defect participating in the
      TS-TPA process is concluded to be promoted by nitrogen incorporation. The
      revealed defect-mediated TS-TPA process can boost efficiency of harvesting solar
      energy in GaNP NWs, beneficial for applications of this novel material system in
      third-generation photovoltaic devices.

PMID- 25045137
TI  - Mild and versatile nitrate-promoted C-H bond fluorination.
AB  - A novel and facile C-H bond fluorination proceeds under remarkably mild
      conditions (close to room temperature in most cases). Both aromatic and olefinic
      C(sp(2))-H bonds with a wide range of electronic properties are selectively
      fluorinated in the presence of a catalytic amount of simple, cheap, and nontoxic
      nitrate as the promoter. A Pd(II)/Pd(IV) catalytic cycle that is initiated by an
      in situ generated cationic [Pd(NO3)](+) species was proposed based on preliminary
      mechanistic studies.

PMID- 25045138
TI  - Lingo-1 inhibited by RNA interference promotes functional recovery of
      experimental autoimmune encephalomyelitis.
AB  - Lingo-1 is a negative regulator of myelination. Repairment of demyelinating
      diseases, such as multiple sclerosis (MS)/experimental autoimmune
      encephalomyelitis (EAE), requires activation of the myelination program. In this
      study, we observed the effect of RNA interference on Lingo-1 expression, and the
      impact of Lingo-1 suppression on functional recovery and
      myelination/remyelination in EAE mice. Lentiviral vectors encoding Lingo-1 short
      hairpin RNA (LV/Lingo-1-shRNA) were constructed to inhibit Lingo-1 expression.
      LV/Lingo-1-shRNA of different titers were transferred into myelin oligodendrocyte
      glycoprotein-induced EAE mice by intracerebroventricular (ICV) injection.
      Meanwhile, lentiviral vectors carrying nonsense gene sequence (LVCON053) were
      used as negative control. The Lingo-1 expression was detected and locomotor
      function was evaluated at different time points (on days 1,3,7,14,21, and 30
      after ICV injection). Myelination was investigated by luxol fast blue (LFB)
      staining.LV/Lingo-1-shRNA administration via ICV injection could efficiently down
      regulate the Lingo-1 mRNA and protein expression in EAE mice on days 7,14,21, and
      30 (P < 0.01), especially in the 5 * 10(8) TU/mL and 5 * 10(9) TU/mL LV/Lingo-1
      shRNA groups. The locomotor function score in the LV/Lingo-1-shRNA treated groups
      were significantly lower than the untreated or LVCON053 group from day 7 on. The
      5 * 10(8) TU/mL LV/Lingo-1-shRNA group achieved the best functional improvement
      (0.87 +/- 0.11 vs. 3.05 +/- 0.13, P < 0.001). Enhanced myelination/remyelination
      was observed in the 5 * 10(7) , 5 * 10(8) , 5 * 10(9) TU/mL LV/Lingo-1-shRNA
      groups by LFB staining (P < 0.05, P < 0.01, and P < 0.05).The data showed that
      administering LV/Lingo-1-shRNA by ICV injection could efficiently knockdown Lingo
      1 expression in vivo, improve functional recovery and enhance
      myelination/remyelination. Antagonism of Lingo-1 by RNA interference is,
      therefore, a promising approach for the treatment of demyelinating diseases, such
      as MS/EAE.

PMID- 25045139
TI  - Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in
      patients with suspected pleural mesothelioma.
AB  - Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to
      asbestos. The prognosis of mesothelioma remains disappointing despite multimodal
      treatment. We reported previously that N-ERC/mesothelin could be a useful
      biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme
      linked immunosorbent assay (ELISA) system for its detection. However, the
      reproducibility of our previous 7-16 ELISA system has been revealed to be
      unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7
      20 ELISA system. The subjects of this study were patients who were referred to
      our department with suspected pleural mesothelioma. The current study
      demonstrated that the newly established 7-20 ELISA system improved the
      sensitivity and specificity for diagnosing pleural mesothelioma compared with the
      previous system. Moreover, the 7-20 ELISA system showed better reproducibility
      and displayed the tendency of both higher sensitivity and higher specificity in
      plasma than in serum. Particularly for the epithelioid type, the area under the
      curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the
      AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma.
      In conclusion, assessment of N-ERC/mesothelin with our newly established 7-20
      ELISA system is clinically useful for the precise diagnosis of pleural
      mesothelioma. 

PMID- 25045140
TI  - Toxicity of triphenyltin chloride to the rotifer Brachionus koreanus across
      different levels of biological organization.
AB  - Although triphenyltin (TPT) compounds are ubiquitous pollutants in urbanised
      coastal environments in Asian regions, their toxicities to marine organisms are
      still poorly known. This study was designed to investigate the toxicity of
      triphenyltin chloride (TPTCl) on the rotifer Brachionus koreanus across different
      levels of biological organisation. Firstly, we concurrently performed a 24 h
      static-acute toxicity test and a 6-day semi-static multigenerational life-cycle
      test using the rotifer. Our results demonstrated that the 24-h median lethal
      concentration of TPTCl for the rotifer was 29.6 MUg/L and the 6-day median effect
      concentration, based on the population growth inhibition, was 3.31 MUg/L.
      Secondly, we examined the expression of 12 heat shock protein (hsp) genes, four
      glutathione S-transferase (GST) genes, one retinoid X receptor (RXR) gene and 13
      cytochrome P450 (CYP) genes in the rotifers after exposure to 20 ug/L TPTCl for
      24 h. Among these studied genes, hsp90alpha2, GST-O and CYP3045C1 were the most
      significantly up-regulated genes with a relative expression level up to 32.9, 4.4
      and 62.6 folds, respectively. The expression of these three genes in the rotifers
      showed an increasing trend in the first few hours of TPTCl exposure, peaked at 3
      h (hsp90alpha2 and GST-O) and 12 h (CYP3045C1) respectively, and then gradually
      returned to a lower level at 24 h. Such up-regulations of hsp and GST genes
      probably offer cellular protection against the TPT-mediated oxidative stress
      while the accelerated induction of CYP genes possibly facilitates the
      detoxification of this toxicant in the rotifer.

PMID- 25045141
TI  - Selective conversion of cellulose in corncob residue to levulinic acid in an
      aluminum trichloride-sodium chloride system.
AB  - Increased energy consumption and environmental concerns have driven efforts to
      produce chemicals from renewable biomass with high selectivity. Here, the
      selective conversion of cellulose in corncob residue, a process waste from the
      production of xylose, to levulinic acid was carried out using AlCl3 as catalyst
      and NaCl as promoter by a hydrothermal method at relatively low temperature. A
      levulinic acid yield of 46.8 mol% was obtained, and the total selectivity to
      levulinic acid with formic acid was beyond 90%. NaCl selectively promoted the
      dissolution of cellulose from corncob residue, and significantly improved the
      yield and selectivity to levulinic acid by inhibiting lactic acid formation in
      the subsequent dehydration process. Owing to the salt effect of NaCl, the
      obtained levulinic acid could be efficiently extracted to tetrahydrofuran from
      aqueous solution. The aqueous solution with AlCl3 and NaCl could be recycled 4
      times. Because of the limited conversion of lignin, this process allows for the
      production of levulinic acid with high selectivity directly from corncob residue
      in a simple separation process.

PMID- 25045142
TI  - Mechanisms of TiO2 nanoparticle-induced neuronal apoptosis in rat primary
      cultured hippocampal neurons.
AB  - Exposure to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to
      decrease learning and memory of animals. However, whether the impacts of these
      NPs on the recognition function are involved in hippocamal neuron damages is
      poorly understood. In this study, primary cultured hippocampal neurons from one
      day-old fetal Sprague-Dawley rats were exposed to 5, 15, or 30 ug/mL TiO2 NPs for
      24 h, we investigated cell viability, ultrastructure, and mitochondrial membrane
      potential (MMP), calcium homeostasis, oxidative stress, antioxidant capacity,
      apoptotic signaling pathway associated with the primary cultured hippocamal
      neuron apoptosis. Our findings showed that TiO2 NP treatment resulted in
      reduction of cell viability, promoted lactate dehydrogenase release, apoptosis,
      and increased neuron apoptotic rate in a dose-dependent manner. Furthermore, TiO2
      NPs led to [Ca(2+)]i elevation, and MMP reduction, up-regulated protein
      expression of cytochrome c, Bax, caspase-3, glucose-regulated protein 78, C/EBP
      homologous protein and caspase-12, and down-regulated bcl-2 expression in the
      primary cultured hippocampal neurons. These findings suggested that hippocampal
      neuron apoptosis caused by TiO2 NPs may be associated with mitochondria-mediated
      signal pathway and endoplasmic reticulum-mediated signal pathway.

PMID- 25045143
TI  - The I=X (X=O,N,C) double bond in hypervalent iodine compounds: is it real?
AB  - I?X (X=O, N, C) bonding was analyzed in the related hypervalent iodine compounds
      based on the adaptive natural density partitioning (AdNDP) approach. The results
      confirm the presence of a I->X sigma dative bond, as opposed to the widely used
      I?X notation. A clear formulation of the electronic structure of these
      hypervalent iodine compounds would be useful in establishing reaction mechanisms
      and electronic structures in bioinorganic problems of general applicability. 

PMID- 25045145
TI  - Cell-surface engineering by a conjugation-and-release approach based on the
      formation and cleavage of oxime linkages upon mild electrochemical oxidation and
      reduction.
AB  - We report a strategy to rewire cell surfaces for the dynamic control of ligand
      composition on cell membranes and the modulation of cell-cell interactions to
      generate three-dimensional (3D) tissue structures applied to stem-cell
      differentiation, cell-surface tailoring, and tissue engineering. We tailored cell
      surfaces with bioorthogonal chemical groups on the basis of a liposome-fusion and
      -delivery method to create dynamic, electroactive, and switchable cell-tissue
      assemblies through chemistry involving chemoselective conjugation and release.
      Each step to modify the cell surface: activation, conjugation, release, and
      regeneration, can be monitored and modulated by noninvasive, label-free
      analytical techniques. We demonstrate the utility of this methodology by the
      conjugation and release of small molecules to and from cell surfaces and by the
      generation of 3D coculture spheroids and multilayered cell tissues that can be
      programmed to undergo assembly and disassembly on demand. 

PMID- 25045144
TI  - A continuous flow strategy for the coupled transfer hydrogenation and
      etherification of 5-(hydroxymethyl)furfural using Lewis acid zeolites.
AB  - Hf-, Zr- and Sn-Beta zeolites effectively catalyze the coupled transfer
      hydrogenation and etherification of 5-(hydroxymethyl)furfural with primary and
      secondary alcohols into 2,5-bis(alkoxymethyl)furans, thus making it possible to
      generate renewable fuel additives without the use of external hydrogen sources or
      precious metals. Continuous flow experiments reveal nonuniform changes in the
      relative deactivation rates of the transfer hydrogenation and etherification
      reactions, which impact the observed product distribution over time. We found
      that the catalysts undergo a drastic deactivation for the etherification step
      while maintaining catalytic activity for the transfer hydrogenation step. (119)
      Sn and (29) Si magic angle spinning (MAS) NMR studies show that this deactivation
      can be attributed to changes in the local environment of the metal sites.
      Additional insights were gained by studying effects of various alcohols and water
      concentration on the catalytic reactivity. 

PMID- 25045146
TI  - Root length of aquatic plant, Lemna minor L., as an optimal toxicity endpoint for
      biomonitoring of mining effluents.
AB  - Lemna minor, a free-floating macrophyte, is used for biomonitoring of mine
      effluent quality under the Metal Mining Effluent Regulations (MMER) of the
      Environmental Effects Monitoring (EEM) program in Canada and is known to be
      sensitive to trace metals commonly discharged in mine effluents such as Ni.
      Environment Canada's standard toxicity testing protocol recommends frond count
      (FC) and dry weight (DW) as the 2 required toxicity endpoints-this is similar to
      other major protocols such as those by the US Environmental Protection Agency
      (USEPA) and the Organisation for Economic Co-operation and Development (OECD)
      that both require frond growth or biomass endpoints. However, we suggest that
      similar to terrestrial plants, average root length (RL) of aquatic plants will be
      an optimal and relevant endpoint. As expected, results demonstrate that RL is the
      ideal endpoint based on the 3 criteria: accuracy (i.e., toxicological sensitivity
      to contaminant), precision (i.e., lowest variance), and ecological relevance
      (metal mining effluents). Roots are known to play a major role in nutrient uptake
      in conditions of low nutrient conditions-thus having ecological relevance to
      freshwater from mining regions. Root length was the most sensitive and precise
      endpoint in this study where water chemistry varied greatly (pH and varying
      concentrations of Ca, Mg, Na, K, dissolved organic carbon, and an anthropogenic
      organic contaminant, sodium isopropyl xanthates) to match mining effluent ranges.
      Although frond count was a close second, dry weight proved to be an unreliable
      endpoint. We conclude that toxicity testing for the floating macrophyte should
      require average RL measurement as a primary endpoint.

PMID- 25045148
TI  - Plasma proteins in the acquired denture pellicle enhance substrate surface free
      energy and Candida albicans phospholipase and proteinase activities.
AB  - AIM: The objective of the present study was to determine if blood plasma proteins
      could change the proteome of the acquired denture pellicle by label-free
      quantitative proteomics. As pellicle proteome modulates the interaction between
      substrates and Candida cells, we investigated its effect on the surface free
      energy (SFE) of the coated resin and on Candida albicans phospholipase and
      aspartyl proteinase activities. METHODS: Poly(methylmethacrylate) discs were
      exposed to saliva (control) or saliva enriched with blood plasma (experimental
      group). The pellicle proteome was analyzed by mass spectrometry coupled with
      liquid chromatography. SFE was determined by acid-base technique. After biofilm
      formation, phospholipase and proteinase activities were determined accordingly to
      classic plate methods. Data were analyzed by two-way anova and Tukey test (P <
      0.05). RESULTS: alpha-Amylase, cystatins, mucins, and host-immune system proteins
      were the main proteins identified in the control group. Fibrinogen and albumin
      were observed only in the experimental group. Coated discs of the experimental
      group presented an increased SFE (P < 0.05). For both enzymes tested, the
      experimental group showed higher proteolytic activity (P < 0.001). CONCLUSION:
      Blood plasma changes the proteome of the acquired denture pellicle, increasing
      surface free energy and the activity of Candida albicans phospholipase and
      aspartyl proteinase.

PMID- 25045149
TI  - Importance of the 6'-hydroxy group and its configuration for apramycin activity.
AB  - A series of apramycin derivatives was prepared and investigated for antibacterial
      activity and the ability to inhibit protein synthesis in cell-free translation
      assays. The effect of various modifications at the 6'- and N7'-positions on
      antiribosomal activity is discussed in terms of their influence on drug binding
      to specific residues in the decoding A-site. These studies contribute to the
      development of a structure-activity relationship for the antibacterial activity
      of the apramycin class of aminoglycosides and to the future design and
      development of more active and less toxic antibiotics.

PMID- 25045147
TI  - Functional repeat-derived RNAs often originate from retrotransposon-propagated
      ncRNAs.
AB  - The human genome is scattered with repetitive sequences, and the ENCODE project
      revealed that 60-70% of the genomic DNA is transcribed into RNA. As a
      consequence, the human transcriptome contains a large portion of repeat-derived
      RNAs (repRNAs). Here, we present a hypothesis for the evolution of novel
      functional repeat-derived RNAs from non-coding RNAs (ncRNAs) by
      retrotransposition. Upon amplification, the ncRNAs can diversify in sequence and
      subsequently evolve new activities, which can result in novel functions. Non
      coding transcripts derived from highly repetitive regions can therefore serve as
      a reservoir for the evolution of novel functional RNAs. We base our hypothetical
      model on observations reported for short interspersed nuclear elements derived
      from 7SL RNA and tRNAs, alpha satellites derived from snoRNAs and SL RNAs derived
      from U1 small nuclear RNA. Furthermore, we present novel putative human repeat
      derived ncRNAs obtained by the comparison of the Dfam and Rfam databases, as well
      as several examples in other species. We hypothesize that novel functional ncRNAs
      can derive also from other repetitive regions and propose Genomic SELEX as a tool
      for their identification.

PMID- 25045150
TI  - Diagnostic whole genome sequencing and split-read mapping for nucleotide
      resolution breakpoint identification in CNTNAP2 deficiency syndrome.
AB  - Whole genome sequencing (WGS) has the potential to report on all types of genetic
      abnormality, thus converging diagnostic testing on a single methodology. Although
      WGS at sufficient depth for robust detection of point mutations is still some way
      from being affordable for diagnostic purposes, low-coverage WGS is already an
      excellent method for detecting copy number variants ("CNVseq"). We report on a
      family in which individuals presented with a presumed autosomal recessive
      syndrome of severe intellectual disability and epilepsy. Array comparative
      genomic hybridization (CGH) analysis had revealed a homozygous deletion
      apparently lying within intron 3 of CNTNAP2. Since this was too small for
      confirmation by FISH, CNVseq was used, refining the extent of this mutation to
      approximately 76.8 kb, encompassing CNTNAP2 exon 3 (an out-of-frame deletion). To
      characterize the precise breakpoints and provide a rapid molecular diagnostic
      test, we resequenced the CNVseq library at medium coverage and performed split
      read mapping. This yielded information for a multiplex polymerase chain reaction
      (PCR) assay, used for cascade screening and/or prenatal diagnosis in this family.
      This example demonstrates a rapid, low-cost approach to converting molecular
      cytogenetic findings into robust PCR-based tests.

PMID- 25045151
TI  - Integrating anatomy training into radiation oncology residency: considerations
      for developing a multidisciplinary, interactive learning module for adult
      learners.
AB  - Radiation oncologists require an in-depth understanding of anatomical
      relationships for modern clinical practice, although most do not receive formal
      anatomy training during residency. To fulfill the need for instruction in
      relevant anatomy, a series of four multidisciplinary, interactive learning
      modules were developed for a cohort of radiation oncology and medical physics
      residents. Instructional design was based on established learning theories, with
      the intent of integrating knowledge of specific anatomical regions with radiology
      and radiation oncology practice. Each session included presentations by a
      radiologist and a radiation oncologist, as well as hands-on exploration of
      anatomical specimens with guidance from anatomists. Pre- and post-tests
      distributed during each session showed significant short-term knowledge
      retention. According to qualitative surveys and exit interviews, participants
      felt more comfort' with delineating structures, gross anatomy, and radiograph
      interpretation at the end of each session. Overall participant experience was
      positive, and the modules were considered effective for learning radiologic
      anatomy. Suggestions for future interventions include more time, increased
      clinical application, additional contouring practice and feedback, and improved
      coordination between each of the three disciplines. Results and conclusions from
      this study will be used to inform the design of a future multi-day national
      workshop for Canadian radiation oncology residents.

PMID- 25045152
TI  - Nutrikinetic modeling reveals order of genistein phase II metabolites appearance
      in human plasma.
AB  - SCOPE: Genistein from foods or supplements is metabolized by the gut microbiota
      and the human body, thereby releasing many different metabolites into systemic
      circulation. The order of their appearance in plasma and the possible influence
      of food format are still unknown. This study compared the nutrikinetic profiles
      of genistein metabolites. METHODS AND RESULTS: In a randomized cross-over trial,
      12 healthy young volunteers were administered a single dose of 30 mg genistein
      provided as a genistein tablet, a genistein tablet in low fat milk, and soy milk
      containing genistein glycosides. A high mass resolution LC-LTQ-Orbitrap FTMS
      platform detected and quantified in human plasma: free genistein, seven of its
      phase-II metabolites and 15 gut-derived metabolites. Interestingly, a novel
      metabolite, genistein-4'-glucuronide-7-sulfate (G-4'G-7S) was identified.
      Nutrikinetic analysis using population-based modeling revealed the order of
      appearance of five genistein phase II metabolites in plasma: (1) genistein-4',7
      diglucuronide, (2) genistein-7-sulfate, (3) genistein-4'-sulfate-7-glucuronide,
      (4) genistein-4'-glucuronide, and (5) genistein-7-glucuronide, independent of the
      food matrix. CONCLUSION: The conjugated genistein metabolites appear in a
      distinct order in human plasma. The specific early appearance of G-4',7-diG
      suggests a multistep formation process for the mono and hetero genistein
      conjugates, involving one or two deglucuronidation steps.

PMID- 25045153
TI  - Current approaches in evolution: from molecules to cells and organisms.
AB  - This is an exciting time to be an evolutionary biologist. Indeed, it is difficult
      to keep up with all the studies that fall under the broad category of "Evolution"
      since they span species, traits, and scales of organization. This special issue
      gives a flavor of exciting new approaches in evolutionary biology, but also
      emphasizes universal themes. The reviews contained here discuss important aspects
      of molecular evolution at multiple scales, from individual proteins to complex
      regulatory networks, as well as from unicellular organisms to macroscopic traits
      in animals. Though the model systems are diverse, the issues addressed are
      fundamental: the origin of evolutionary novelties, and the forces that drive them
      to fixation.

PMID- 25045154
TI  - Acute liver allograft antibody-mediated rejection: an inter-institutional study
      of significant histopathological features.
AB  - Acute antibody-mediated rejection (AMR) occurs in a small minority of sensitized
      liver transplant recipients. Although histopathological characteristics have been
      described, specific features that could be used (1) to make a generalizable
      scoring system and (2) to trigger a more in-depth analysis are needed to screen
      for this rare but important finding. Toward this goal, we created training and
      validation cohorts of putative acute AMR and control cases from 3 high-volume
      liver transplant programs; these cases were evaluated blindly by 4 independent
      transplant pathologists. Evaluations of hematoxylin and eosin (H&E) sections were
      performed alone without knowledge of either serum donor-specific human leukocyte
      antigen alloantibody (DSA) results or complement component 4d (C4d) stains.
      Routine histopathological features that strongly correlated with severe acute AMR
      included portal eosinophilia, portal vein endothelial cell hypertrophy,
      eosinophilic central venulitis, central venulitis severity, and cholestasis.
      Acute AMR inversely correlated with lymphocytic venulitis and lymphocytic portal
      inflammation. These and other characteristics were incorporated into models
      created from the training cohort alone. The final acute antibody-mediated
      rejection score (aAMR score)--the sum of portal vein endothelial cell
      hypertrophy, portal eosinophilia, and eosinophilic venulitis divided by the sum
      of lymphocytic portal inflammation and lymphocytic venulitis--exhibited a strong
      correlation with severe acute AMR in the training cohort [odds ratio (OR) = 2.86,
      P < 0.001] and the validation cohort (OR = 2.49, P < 0.001). SPSS tree
      classification was used to select 2 cutoffs: one that optimized specificity at a
      score > 1.75 (sensitivity = 34%, specificity = 86%) and another that optimized
      sensitivity at a score > 1.0 (sensitivity = 81%, specificity = 71%). In
      conclusion, the routine histopathological features of the aAMR score can be used
      to screen patients for acute AMR via routine H&E staining of indication liver
      transplant biopsy samples; however, a definitive diagnosis requires
      substantiation by DSA testing, diffuse C4d staining, and the exclusion of other
      insults.

PMID- 25045155
TI  - Recognition of the DNA minor groove by thiazotropsin analogues.
AB  - Solution-phase self-association characteristics and DNA molecular-recognition
      properties are reported for three close analogues of minor-groove-binding ligands
      from the thiazotropsin class of lexitropsin molecules; they incorporate isopropyl
      thiazole as a lipophilic building block. Thiazotropsin B (AcImPy(iPr) ThDp) shows
      similar self-assembly characteristics to thiazotropsin A (FoPyPy(iPr) ThDp),
      although it is engineered, by incorporation of imidazole in place of N-methyl
      pyrrole, to swap its DNA recognition target from 5'-ACTAGT-3' to 5'-ACGCGT-3'.
      Replacement of the formamide head group in thiazotropsin A by nicotinamide in AIK
      18/51 results in a measureable difference in solution-phase self-assembly
      character and substantially enhanced DNA association characteristics. The
      structures and associated thermodynamic parameters of self-assembled ligand
      aggregates and their complexes with their respective DNA targets are considered
      in the context of cluster targeting of DNA by minor-groove complexes. 

PMID- 25045156
TI  - Hierarchical logic structures based on responsive fluorescent gold nanoclusters.
AB  - Logic with Gold Clusters. Gold nanoclusters can be used for the development of
      hierarchical logic structures. This is based on the reversible change in the
      fluorescence of the clusters at different pH of the medium, its temperature and
      metal ion concentration dependence. 

PMID- 25045157
TI  - Impact of adverse events, treatment modifications, and dose intensity on survival
      among patients with advanced renal cell carcinoma treated with first-line
      sunitinib: a medical chart review across ten centers in five European countries.
AB  - Angiogenesis inhibitors have become standard of care for advanced and/or
      metastatic renal cell carcinoma (RCC), but data on the impact of adverse events
      (AEs) and treatment modifications associated with these agents are limited.
      Medical records were abstracted at 10 tertiary oncology centers in Europe for 291
      patients >= 18 years old treated with sunitinib as first-line treatment for
      advanced RCC (no prior systemic treatment for advanced disease). Logistic
      regression models were estimated to compare dose intensity among patients who did
      and did not experience AEs during the landmark periods (18, 24, and 30 weeks).
      Cox proportional hazard models were used to explore the possible relationship of
      low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment
      modifications during the landmark periods to survival. 64.4% to 67.9% of patients
      treated with sunitinib reported at least one AE of any grade, and approximately
      10% of patients experienced at least one severe (grade 3 or 4) AE. Patients
      reporting severe AEs were statistically significantly more likely to have dose
      intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose
      discontinuation during all landmark periods were statistically significantly
      associated with shorter survival time. This study of advanced RCC patients
      treated with sunitinib in Europe found a significant relationship between AEs and
      dose intensity. It also found correlations between dose intensity and shorter
      survival, and between dose discontinuation and shorter survival. These results
      confirm the importance of tolerable treatment and maintaining dose intensity.

PMID- 25045158
TI  - Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in
      human airway epithelial cells.
AB  - Increasing use of biodiesel has prompted research into the potential health
      effects of biodiesel exhaust exposure. Few studies directly compare the health
      consequences of mineral diesel, biodiesel, or blend exhaust exposures. Here, we
      exposed human epithelial cell cultures to diluted exhaust generated by the
      combustion of Australian ultralow-sulfur-diesel (ULSD), unprocessed canola oil,
      100% canola biodiesel (B100), and a blend of 20% canola biodiesel mixed with 80%
      ULSD. The physicochemical characteristics of the exhaust were assessed and we
      compared cellular viability, apoptosis, and levels of interleukin (IL)-6, IL-8,
      and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) in
      exposed cultured cells. Different fuel types produced significantly different
      amounts of exhaust gases and different particle characteristics. All exposures
      resulted in significant apoptosis and loss of viability when compared with
      control, with an increasing proportion of biodiesel being correlated with a
      decrease in viability. In most cases, exposure to exhaust resulted in an increase
      in mediator production, with the greatest increases most often in response to
      B100. Exposure to pure canola oil (PCO) exhaust did not increase mediator
      production, but resulted in a significant decrease in IL-8 and RANTES in some
      cases. Our results show that canola biodiesel exhaust exposure elicits
      inflammation and reduces viability of human epithelial cell cultures in vitro
      when compared with ULSD exhaust exposure. This may be related to an increase in
      particle surface area and number in B100 exhaust when compared with ULSD exhaust.
      Exposure to PCO exhaust elicited the greatest loss of cellular viability, but
      virtually no inflammatory response, likely due to an overall increase in average
      particle size.

PMID- 25045159
TI  - TiO2-coated CoCrMo: improving the osteogenic differentiation and adhesion of
      mesenchymal stem cells in vitro.
AB  - The current gold standard material for orthopedic applications is titanium (Ti),
      however, other materials such as cobalt-chromium-molybdenum (CoCrMo) are often
      preferred due to their wear resistance and mechanical strength. This study
      investigates if the bioactivity of CoCrMo can be enhanced by coating the surface
      with titanium oxide (TiO2 ) by atmospheric pressure chemical vapor deposition
      (CVD), thereby replicating the surface oxide layer found on Ti. CoCrMo, TiO2
      coated CoCrMo (CCMT) and Ti substrates were used for this study. Cellular f-actin
      distribution was shown to be noticeably different between cells on CCMT and
      CoCrMo after 24 h in osteogenic culture, with cells on CCMT exhibiting greater
      spread with developed protrusions. Osteogenic differentiation was shown to be
      enhanced on CCMT compared to CoCrMo, with increased calcium ion content per cell
      (p < 0.05), greater hydroxyapatite nodule formation (p < 0.05) and reduced type I
      collagen deposition per cell (p < 0.05). The expression of the focal adhesion
      protein vinculin was shown to be marginally greater on CCMT compared to CoCrMo,
      whereas AFM results indicated that CCMT required more force to remove a single
      cell from the substrate surface compared to CoCrMo (p < 0.0001). These data
      suggest that CVD TiO2 coatings may have the potential to increase the
      biocompatibility of CoCrMo implantable devices.

PMID- 25045160
TI  - SCAI expert consensus statement for infrapopliteal arterial intervention
      appropriate use.
AB  - Intervention to treat infrapopliteal arterial disease can be challenging because
      the patients' comorbidities, the anatomic variables, and the limitations of our
      techniques. Clinical scenarios based on anatomic and clinical variables are
      presented. Recommendations regarding intervention (appropriate care, may be
      appropriate care, rarely appropriate care) are made based on best evidence.

PMID- 25045161
TI  - Synthesis of bio-based methacrylic acid by decarboxylation of itaconic acid and
      citric acid catalyzed by solid transition-metal catalysts.
AB  - Methacrylic acid, an important monomer for the plastics industry, was obtained in
      high selectivity (up to 84%) by the decarboxylation of itaconic acid using
      heterogeneous catalysts based on Pd, Pt and Ru. The reaction takes place in water
      at 200-250  degrees C without any external added pressure, conditions
      significantly milder than those described previously for the same conversion with
      better yield and selectivity. A comprehensive study of the reaction parameters
      has been performed, and the isolation of methacrylic acid was achieved in 50%
      yield. The decarboxylation procedure is also applicable to citric acid, a more
      widely available bio-based feedstock, and leads to the production of methacrylic
      acid in one pot in 41% selectivity. Aconitic acid, the intermediate compound in
      the pathway from citric acid to itaconic acid was also used successfully as a
      substrate.

PMID- 25045162
TI  - Validation of the Malay version of the Modified Dental Anxiety Scale and the
      prevalence of dental anxiety in a Malaysian population.
AB  - AIM: The aims of the present study were to evaluate the reliability and validity
      of the Malay version of the Modified Dental Anxiety Scale (MDAS), and to
      determine the prevalence of dental anxiety and associated factors in a Malaysian
      population. METHODS: A Malay-language questionnaire with questions to elicit
      demographic and dental care-related information, and the Malay version of the
      MDAS, were administered to 455 patients at the dental outpatient clinics of the
      Hospital Universiti Sains Malaysia. Factor analysis and internal consistency
      statistics were generated. A test-retest of the questionnaire was performed with
      30 participants. RESULTS: Cronbach's alpha was 0.854, indicating good internal
      consistency. Factor analysis yielded results showing good validity. Approximately
      3.5% of the participants expressed the highest levels of anxiety. Dental anxiety
      was significantly higher among females than males. Age correlated inversely with
      dental anxiety. Individuals seeking dental care only if a problem appeared had
      significantly more anxiety than regular attendees. Patients who postponed
      treatment because of fear had significantly higher anxiety levels than those who
      delayed treatment for other reasons. Past adverse dental experience exacerbated
      dental anxiety. CONCLUSION: The Malay version of the MDAS had good reliability
      and validity. Anxiety levels found in the Malaysians studied were comparable to
      participants from other countries.

PMID- 25045163
TI  - Novel viral translation strategies.
AB  - Viral genomes are compact and encode a limited number of proteins. Because they
      do not encode components of the translational machinery, viruses exhibit an
      absolute dependence on the host ribosome and factors for viral messenger RNA
      (mRNA) translation. In order to recruit the host ribosome, viruses have evolved
      unique strategies to either outcompete cellular transcripts that are efficiently
      translated by the canonical translation pathway or to reroute translation factors
      and ribosomes to the viral genome. Furthermore, viruses must evade host antiviral
      responses and escape immune surveillance. This review focuses on some recent
      major findings that have revealed unconventional strategies that viruses utilize,
      which include usurping the host translational machinery, modulating canonical
      translation initiation factors to specifically enhance or repress overall
      translation for the purpose of viral production, and increasing viral coding
      capacity. The discovery of these diverse viral strategies has provided insights
      into additional translational control mechanisms and into the viral host
      interactions that ensure viral protein synthesis and replication.

PMID- 25045164
TI  - Drastic stabilization of parallel DNA hybridizations by a polylysine comb-type
      copolymer with hydrophilic graft chain.
AB  - Electrostatic interactions play a major role in protein-DNA interactions. As a
      model system of a cationic protein, herein we focused on a comb-type copolymer of
      a polycation backbone and dextran side chains, poly(L-lysine)-graft-dextran (PLL
      g-Dex), which has been reported to form soluble interpolyelectrolyte complexes
      with DNA strands. We investigated the effects of PLL-g-Dex on the conformation
      and thermodynamics of DNA oligonucleotides forming various secondary structures.
      Thermodynamic analysis of the DNA structures showed that the parallel
      conformations involved in both DNA duplexes and triplexes were significantly and
      specifically stabilized by PLL-g-Dex. On the basis of thermodynamic parameters,
      it was further possible to design DNA switches that undergo structural transition
      responding to PLL-g-Dex from an antiparallel duplex to a parallel triplex even
      with mismatches in the third strand hybridization. These results suggest that
      polycationic molecules are able to induce structural polymorphism of DNA
      oligonucleotides, because of the conformation-selective stabilization effects.

PMID- 25045165
TI  - Microbial catabolism of procyanidins by human gut microbiota.
AB  - SCOPE: A major portion of ingested procyanidins is degraded by human microbiota
      in the colon into various phenolic compounds. These microbial metabolites are
      thought to contribute to the health benefits of procyanidins in vivo. The
      objective of this study was to identify and quantify the microbial metabolites of
      procyanidins after anaerobic fermentation with human microbiota. METHODS AND
      RESULTS: (-)-Epicatechin, (+)-catechin, procyanidin B2, procyanidin A2, partially
      purified apple and cranberry procyanidins were incubated with human microbiota at
      a concentration equivalent to 0.5 mM epicatechin. GC-MS analysis showed that
      common metabolites of all six substrates were benzoic acid, 2-phenylacetic acid,
      3-phenylpropionic acid, 2-(3'-hydroxyphenyl)acetic acid, 2-(4'
      hydroxyphenyl)acetic acid, 3-(3'-hydroxyphenyl)propionic acid, and
      hydroxyphenylvaleric acid. 5-(3',4'-Dihydroxyphenyl)-gamma-valerolactones and 5
      (3'-hydroxyphenyl)-gamma-valerolactones were identified as the microbial
      metabolites of epicatechin, catechin, procyanidin B2, and apple procyanidins but
      not from the procyanidin A2 or cranberry procyanidin ferments. 2-(3',4'
      Dihydroxyphenyl)acetic acid was only found in the fermented broth of procyanidin
      B2, A2, apple, and cranberry procyanidins. The mass recoveries of microbial
      metabolites range from 20.0 to 56.9% for the six substrates after 24 h of
      fermentation. CONCLUSION: Procyanidins, both B-type and A-type can be degraded by
      human gut microbiota. The microbial metabolites may contribute to the
      bioactivities of procyanidins.

PMID- 25045166
TI  - Aspirin versus anticoagulation for prevention of venous thromboembolism major
      lower extremity orthopedic surgery: a systematic review and meta-analysis.
AB  - BACKGROUND: Hip fracture surgery and lower extremity arthroplasty are associated
      with increased risk of both venous thromboembolism and bleeding. The best
      pharmacologic strategy for reducing these opposing risks is uncertain. PURPOSE:
      To compare venous thromboembolism (VTE) and bleeding rates in adult patients
      receiving aspirin versus anticoagulants after major lower extremity orthopedic
      surgery. DATA SOURCES: Medline, Cumulative Index to Nursing and Allied Health
      Literature, and the Cochrane Library through June 2013; reference lists,
      ClinicalTrials.gov, and scientific meeting abstracts. STUDY SELECTION: Randomized
      trials comparing aspirin to anticoagulants for prevention of VTE following major
      lower extremity orthopedic surgery. DATA EXTRACTION: Two reviewers independently
      extracted data on rates of VTE, bleeding, and mortality. DATA SYNTHESIS: Of 298
      studies screened, 8 trials including 1408 participants met inclusion criteria;
      all trials screened participants for deep venous thrombosis (DVT). Overall rates
      of DVT did not differ statistically between aspirin and anticoagulants (relative
      risk [RR]: 1.15 [95% confidence interval {CI}: 0.68-1.96]). Subgrouped by type of
      surgery, there was a nonsignificant trend favoring anticoagulation following hip
      fracture repair but not knee or hip arthroplasty (hip fracture RR: 1.60 [95% CI:
      0.80-3.20], 2 trials; arthroplasty RR: 1.00 [95% CI: 0.49-2.05], 5 trials). The
      risk of bleeding was lower with aspirin than anticoagulants following hip
      fracture repair (RR: 0.32 [95% CI: 0.13-0.77], 2 trials), with a nonsignificant
      trend favoring aspirin after arthroplasty (RR: 0.63 [95% CI: 0.33-1.21], 5
      trials). Rates of pulmonary embolism were too low to provide reliable estimates.
      CONCLUSION: Compared with anticoagulation, aspirin may be associated with higher
      risk of DVT following hip fracture repair, although bleeding rates were
      substantially lower. Aspirin was similarly effective after lower extremity
      arthroplasty and may be associated with lower bleeding risk. Journal of Hospital
      Medicine 2014;9:579-585. (c) 2014 Society of Hospital Medicine.

PMID- 25045167
TI  - Acute and chronic postsurgical pain after living liver donation: Incidence and
      predictors.
AB  - Despite its prominence as a concern among potential surgical candidates, there is
      little information in the literature regarding the short- and long-term pain
      experience after living liver donation. We undertook a prospective study to
      examine (1) the nature and incidence of acute and chronic pain after living donor
      hepatectomy and (2) the factors associated with an increased or decreased risk of
      adverse pain outcomes. Before donation, a comprehensive assessment of potential
      predictors of acute and chronic pain outcomes was conducted; this included
      donors' pain expectations, psychosocial factors, medical histories, and
      demographic factors. Detailed data regarding pain outcomes were collected
      postoperatively (days 1 and 2) and again during 6- and 12-month follow-up
      telephone interviews. Sixty-five adults (32 females and 33 males) scheduled for
      donor hepatectomy participated. Substantial proportions of the donors reported a
      moderate-to-severe level of pain intensity (>=4 on a 0-10 scale) at rest and
      after movement on day 1 (42% and 74%, respectively) and day 2 (33% and 32%,
      respectively). Persistent postsurgical pain was reported by 31% of the donors at
      the 6-month follow-up and by 27% of the donors at the 12-month follow-up.
      Generally, this pain was mild, and pain-related life interference was minimal.
      Female sex, a younger age, and several predonation measures of pain-related
      anxiety were associated with a significantly greater risk of developing
      persistent postsurgical pain. In conclusion, this study has identified a subset
      of patients who experience persistent pain after living liver donation.
      Additional prospective research using larger samples of liver donors is needed to
      replicate this work, to obtain a more detailed account of the acute and long-term
      pain experience, and to determine whether targeted interventions can minimize the
      frequency and severity of chronic pain.

PMID- 25045168
TI  - Adhesive bonding to pulp chamber dentin after different irrigation regimens.
AB  - AIM: The aim of the present study was to determine the effect of
      ethylenediaminetetraacetic acid (EDTA) and NaOCl irrigation on the microleakage
      and interfacial morphology of adhesives bonded to pulp chamber dentin. METHODS:
      The pulp chamber roof of 72 extracted permanent molars was removed. Samples were
      equally divided into six groups. Pulp chamber dentin was bonded with either Adper
      Easy One (group 1), Adper Prompt L-Pop (group 2), or Adper Single Bond 2 (Group
      3), after irrigation with either normal saline (groups 1a, 2a, 3a) or 17% EDTA
      and 5.25% NaOCl (groups 1b, 2b, 3b). Composite resin restorations were placed in
      the pulp chamber. Ten samples per group were subjected to microleakage test and
      scanning electron microscopic analysis was done in two samples from each group.
      Data were statistically analyzed using Mann-Whitney and Kruskal Wallis tests at a
      significance level of P < 0.05. RESULTS: EDTA and NaOCl irrigation of the pulp
      chamber significantly reduced microleakage in Adper Easy One. However, it had no
      significant effect on the microleakage of Adper Prompt L-Pop and Adper Single
      Bond 2. CONCLUSIONS: EDTA and NaOCl irrigation of the pulp chamber was not
      deleterious to the bonding of any of the adhesives tested. While this irrigation
      regimen had no significant effect on the microleakage of Adper Prompt L-Pop and
      Adper Single Bond 2, it significantly reduced the microleakage scores in Adper
      Easy One.

PMID- 25045169
TI  - Effects of Regioselectivity and Lipid Class Specificity of Lipases on
      Transesterification, Exemplified by Biodiesel Production.
AB  - Lipase-catalyzed ethanolysis of triolein was studied as a model for biodiesel
      production. Four lipases were immobilized on porous polypropylene, and
      ethanolysis reactions were carried out in methyl t-butyl ether. The reaction
      products were analyzed using gas chromatography. Three of the four lipases
      studied were efficient in the conversion of triolein to 2-monoolein, but slow in
      the final step of producing glycerol. However, Candida antarctica lipase B was
      slow in the conversion of triolein, but more efficient in the subsequent two
      steps than the other lipases. The 1,3-selectivity of the lipases was less
      pronounced for the monooleins than for triolein. Silica gel was investigated as a
      catalyst for acyl migration, showing an increase in biodiesel yield with three of
      the lipases, but a reduction in yield when C. antarctica lipase B was used. The
      highest biodiesel yield (96 %) was obtained with a combination of Rhizopus
      arrhizus lipase and C. antarctica lipase B.

PMID- 25045171
TI  - New insights into the hormonal and behavioural correlates of polymorphism in
      white-throated sparrows, Zonotrichia albicollis.
AB  - The white-throated sparrow is a promising model for behavioural
      neuroendocrinology and genetics because behaviour and endocrine function may be
      linked to a chromosomal rearrangement that determines plumage colour. The notion
      that the two colour morphs, tan-striped (TS) and white-striped (WS), differ
      predictably in aggression and parenting has been widely accepted, despite
      conflicting evidence. It is also hypothesized that morph-typic behaviour is
      hormone mediated, yet no field study has measured sex steroids and behaviour in
      the same birds. Here, we re-evaluate the TS and WS phenotypes, describe the
      conditions under which they differ and investigate relationships between sex
      steroids and behaviour. We report that (1) during territorial intrusions, WS
      males were more aggressive than TS birds, but this difference was restricted to
      singing; WS males sang more than TS males but showed identical levels of physical
      aggression. WS females sang more than TS females and were also more physically
      aggressive. (2) TS males provisioned young more frequently than did WS males, but
      only during first broods. The parental strategy of WS males was flexible, and
      during replacement broods, WS and TS males provisioned at equal rates. (3)
      Consistent with previous studies, we detected no morph difference in female
      provisioning. (4) Plasma testosterone and dihydrotestosterone were higher in WS
      males than in TS males during periods of peak territorial defence and during
      first broods; within breeding stages, male androgen levels were positively
      correlated with singing and negatively correlated with provisioning. Plasma
      oestradiol levels were higher in WS females than in TS females and higher during
      peak territorial defence; oestradiol levels tended to be positively correlated
      with singing. Overall, our results refine the TS and WS phenotypes, show that
      behavioural differences between them are restricted to periods with relatively
      high mating opportunity, and demonstrate an association between sex steroids and
      morph-typic behaviour. These results will inform future studies of this promising
      model.

PMID- 25045170
TI  - RECENT ADVANCES IN ULTRA-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY FOR THE ANALYSIS
      OF TRADITIONAL CHINESE MEDICINE.
AB  - Traditional Chinese medicine has been widely used for the prevention and
      treatment of various diseases for thousands of years in China. Ultra-high
      performance liquid chromatography (UHPLC) is a relatively new technique offering
      new possibilities. This paper reviews recent developments in UHPLC in the
      separation and identification, fingerprinting, quantification, and metabolism of
      traditional Chinese medicine. Recently, the combination of UHPLC with MS has
      improved the efficiency of the analysis of these materials.

PMID- 25045172
TI  - Reduced rank regression via adaptive nuclear norm penalization.
AB  - We propose an adaptive nuclear norm penalization approach for low-rank matrix
      approximation, and use it to develop a new reduced rank estimation method for
      high-dimensional multivariate regression. The adaptive nuclear norm is defined as
      the weighted sum of the singular values of the matrix, and it is generally non
      convex under the natural restriction that the weight decreases with the singular
      value. However, we show that the proposed non-convex penalized regression method
      has a global optimal solution obtained from an adaptively soft-thresholded
      singular value decomposition. The method is computationally efficient, and the
      resulting solution path is continuous. The rank consistency of and
      prediction/estimation performance bounds for the estimator are established for a
      high-dimensional asymptotic regime. Simulation studies and an application in
      genetics demonstrate its efficacy.

PMID- 25045173
TI  - Religion and Early Marriage in the United States: Evidence from the Add Health
      Study.
AB  - Early marriage has important consequences for individuals in the United States.
      Several studies have linked religion to early marriage but have not examined this
      relationship in depth. Using data from Waves 1, 3, and 4 of the National
      Longitudinal Study of Adolescent Health, I conduct multilevel event-history
      analysis to examine how religion, at both individual and contextual levels, is
      associated with early marriage. Further, I test mediators of the religion-early
      marriage relationship. I find significant variation in early marriage by
      religious tradition, religious service attendance, religious salience, belief in
      scriptural inerrancy, and religious context in high school. The individual
      religious effects-but not the school context effects-are explained in part by
      differential attitudes toward marriage and cohabitation.

PMID- 25045174
TI  - Paternal Hostility and Maternal Hostility in European American and African
      American Families.
AB  - The authors examined the hypothesized influence of maternal and paternal
      hostility on youth delinquency over time. The investigation addressed significant
      gaps in earlier research on parental hostility, including the neglect of father
      effects, especially in African American families. Using prospective, longitudinal
      data from community samples of European American (n = 422) and African American
      (n = 272) 2-parent families, the authors examined the independent effects of
      paternal and maternal hostility on youth delinquency. The results indicated that
      paternal hostility significantly predicted relative increases in youth delinquent
      behaviors above and beyond the effects of maternal hostility; conversely,
      maternal hostility did not predict youth delinquency after controlling for
      paternal hostility. Multiple-group analyses yielded similar results for both
      ethnic groups and for boys and girls. These results underscore the importance of
      including both parents in research on diverse families. Neglecting fathers
      provides an incomplete account of parenting in relation to youth development.

PMID- 25045175
TI  - His and Hers: Economic Factors and Relationship Quality in Germany.
AB  - Research has linked economic factors to relationship quality in the United
      States, primarily using cross-sectional data. In the current study, 2 waves of
      the Panel Analysis of Intimate Relationships and Family Dynamics data (n = 2,937)
      were used to test the gendered association between economic factors and
      relationship satisfaction among young German couples. In contrast to U.S.-based
      studies, the findings showed striking gender differences in the association
      between economic factors and relationship satisfaction for Germans. In cross
      sectional models, women's relationship satisfaction was positively associated
      with receiving government economic support, and men's satisfaction was positively
      associated with poverty status and negatively associated with being a
      breadwinner. Longitudinal models revealed that changes in poverty status are
      associated with women's satisfaction, but men's satisfaction remains tied to
      their role as family provider. These unexpected results suggest that men's
      satisfaction is positively associated with a more equal division of labor market
      activity between partners.

PMID- 25045177
TI  - The 'morbid anatomy' of the human genome: tracing the observational and
      representational approaches of postwar genetics and biomedicine the William Bynum
      Prize Essay.
AB  - This paper explores evolving conceptions and depictions of the human genome among
      human and medical geneticists during the postwar period. Historians of science
      and medicine have shown significant interest in the use of informational
      approaches in postwar genetics, which treat the genome as an expansive digital
      data set composed of three billion DNA nucleotides. Since the 1950s, however,
      geneticists have largely interacted with the human genome at the microscopically
      visible level of chromosomes. Mindful of this, I examine the observational and
      representational approaches of postwar human and medical genetics. During the
      1970s and 1980s, the genome increasingly came to be understood as, at once, a
      discrete part of the human anatomy and a standardised scientific object. This
      paper explores the role of influential medical geneticists in recasting the human
      genome as being a visible, tangible, and legible entity, which was highly
      relevant to traditional medical thinking and practice. I demonstrate how the
      human genome was established as an object amenable to laboratory and clinical
      research, and argue that the observational and representational approaches of
      postwar medical genetics reflect, more broadly, the interdisciplinary efforts
      underlying the development of contemporary biomedicine.

PMID- 25045176
TI  - Stress and coping in interracial contexts: The influence of race-based rejection
      sensitivity and cross-group friendship in daily experiences of health.
AB  - We examined the interplay of psychosocial risk and protective factors in daily
      experiences of health. In Study 1, the tendency to anxiously expect rejection
      from racial outgroup members, termed race-based rejection sensitivity (RS-race),
      was cross-sectionally related to greater stress-symptoms among Black adults who
      reported fewer cross-race friends but not among participants who had more cross
      race friends. In Study 2, we experimentally manipulated the development of a same
      versus cross-race friendship among Latino/a-White dyads prior to collecting
      daily experiences of stress-symptoms using a diary methodology. While RS-race
      predicted more psychosomatic symptoms in the same-race friendship condition, RS
      race was unrelated to symptomatology among participants who made a cross-race
      friend. These findings suggest that experiences of intergroup stress can spill
      over into everyday life in the absence of positive contact, but cross-race
      friendships may be a resource that mitigates the expression of interracial
      stress.

PMID- 25045178
TI  - Clinical experience in late antiquity: Alexander of Tralles and the therapy of
      epilepsy.
AB  - Alexander of Tralles, writing in the late sixth century, combined his wide
      ranging practical knowledge with earlier medical theories. This article shows how
      clinical experience is used in Alexander's works by concentrating on his
      therapeutic advice on epilepsy and, in particular, on pharmacology and the group
      of so-called natural remedies. I argue that clinical testing is used not only for
      the introduction of new medicines but also as an instrument for checking the
      therapeutic effect of popular healing practices. On another level, this article
      discusses Alexander's role as the author of a medical compendium; it suggests
      that by marking the cases of clinical testing with a set of recurrent
      expressions, Alexander leads his audience to reflect on his medical authority and
      personal contribution. 

PMID- 25045179
TI  - Making modern migraine medieval: men of science, Hildegard of Bingen and the life
      of a retrospective diagnosis.
AB  - Charles Singer's retrospective diagnosis of Hildegard of Bingen as a migraine
      sufferer, first made in 1913, has become commonly accepted. This article uses
      Hildegard as a case study to shift our focus from a polarised debate about the
      merits or otherwise of retrospective diagnosis, to examine instead what happens
      when diagnoses take on lives of their own. It argues that simply championing or
      rejecting retrospective diagnosis is not enough; that we need instead to
      appreciate how, at the moment of creation, a diagnosis reflects the significance
      of particular medical signs and theories in historical context and how, when and
      why such diagnoses can come to do meaningful work when subsequently mobilised as
      scientific 'fact'. This article first traces the emergence of a new formulation
      of migraine in the nineteenth century, then shows how this context enabled Singer
      to retrospectively diagnose Hildegard's migraine and finally examines some of the
      ways in which this idea has gained popular and academic currency in the second
      half of the twentieth century. The case of Hildegard's migraine reminds us of the
      need to historicise scientific evidence just as rigorously as we historicise our
      other material and it exposes the cumulative methodological problems that can
      occur when historians use science, and scientists use history on a casual basis. 

PMID- 25045180
TI  - Paracelsian medicine and theory of generation in 'exterior homo', a manuscript
      probably authored by Jan Baptist Van Helmont (1579-1644).
AB  - This article discusses a Latin manuscript that can be found in the Jan Baptist
      Van Helmont (1579-1644) archives in Mechelen (Malines), Belgium. The manuscript
      bears no author and no title, and begins with the words 'Exterior homo', hence
      being referred by this provisional title in the analysis. Ecclesiastical
      prosecutors investigating Van Helmont for heresy in 1634 considered that it was
      written by him, but this was vehemently denied by the Flemish physician. The
      present article takes a first detailed look at the content of the treatise and
      ideas contained therein. It hence identifies the manuscript as belonging to a
      seventeenth-century physician influenced by the ideas of Theophrastus Paracelsus
      (1493-1541) and his interpreter Petrus Severinus (1542-1602), and containing a
      complex medical philosophy drawn on alchemical thought. Thus, the anonymous
      author presents a comprehensive view on the nature and structure of man, as well
      as an idiosyncratic theory of human generation. Following the analysis of the
      treatise, the article further compares it with the known works of J.B. Van
      Helmont, and finds that it is very similar to his ideas. Hence, the article
      concludes that it is 'likely' that the manuscript is indeed written by Van
      Helmont, although lack of direct evidence prevents certain attribution. 

PMID- 25045181
TI  - 'To preserve the skin in health': drainage, bodily control and the visual
      definition of healthy skin 1835-1900.
AB  - The concept of a healthy skin penetrated the lives of many people in late
      nineteenth-century Britain. Popular writings on skin and soap advertisements are
      significant for pointing to the notions of the skin as a symbolic surface: a
      visual moral ideal. Popular health publications reveal how much contemporary
      understanding of skin defined and connected ideas of cleanliness and the visual
      ideals of the healthy body in Victorian Britain. Characterised as a 'sanitary
      commissioner' of the body, skin represented the organ of drainage for body and
      society. The importance of keeping the skin clean and purging it of waste
      materials such as sweat and dirt resonated in a Britain that embraced city
      sanitation developments, female beauty practices, racial identities and moral
      reform. By focusing on the popular work by British surgeon and dermatologist
      Erasmus Wilson (1809-84), this article offers a history of skin through the lens
      of the sanitary movement and developments in the struggle for control over
      healthy skin still in place today. 

PMID- 25045182
TI  - Healthcare and warfare. Medical space, mission and apartheid in twentieth century
      northern Namibia.
AB  - In the year 1966, the first government hospital, Oshakati hospital, was
      inaugurated in northern South-West Africa. It was constructed by the apartheid
      regime of South Africa which was occupying the territory. Prior to this
      inauguration, Finnish missionaries had, for 65 years, provided healthcare to the
      indigenous people in a number of healthcare facilities of which Onandjokwe
      hospital was the most important. This article discusses these two agents'
      ideological standpoints. The same year, the war between the South-West African
      guerrillas and the South African state started, and continued up to 1988. The two
      hospitals became involved in the war; Oshakati hospital as a part of the South
      African war machinery, and Onandjokwe hospital as a 'terrorist hospital' in the
      eyes of the South Africans. The missionary Onandjokwe hospital was linked to the
      Lutheran church in South-West Africa, which became one of the main critics of the
      apartheid system early in the liberation war. Warfare and healthcare became
      intertwined with apartheid policies and aggression, materialised by healthcare
      provision based on strategic rationales rather than the people's healthcare
      needs. When the Namibian state took over a ruined healthcare system in 1990, the
      two hospitals were hubs in a healthcare landscape shaped by missionary ambitions,
      war and apartheid logic. 

PMID- 25045185
TI  - Controlling Relations in Stimulus Equivalence Classes of Preschool Children and
      Individuals with Down Syndrome.
AB  - We evaluated emergent stimulus-stimulus relations after two different training
      procedures. Participants were five typically developing preschool children and
      three individuals with Down Syndrome. Experiment 1 used two-comparison matching
      to sample (MTS) to establish AB and BC relations. Experiment 2 used two
      comparison and blank-comparison MTS, each on 50% of training trials to establish
      AB and BC relations. In both experiments, tests for emergent relations (AC, CA)
      were conducted to assess equivalence class formation. In Experiment 2
      subsequently, class expansion was assessed after CD training. All participants
      showed positive equivalence test outcomes. Seven showed class expansion. After
      class formation tests in both studies, probe tests were conducted for select and
      reject relations in baseline relations. Initial results were somewhat variable,
      but became more consistent after class expansion.

PMID- 25045186
TI  - Longitudinal Relations Between Parental Writing Support and Preschoolers'
      Language and Literacy Skills.
AB  - Parental writing support was examined over time and in relation to children's
      language and literacy skills. Seventy-seven parents and their preschoolers were
      videotaped writing an invitation together twice during one year. Parental writing
      support was coded at the level of the letter to document parents' graphophonemic
      support (letter-sound correspondence), print support (letter formation), and
      demand for precision (expectation for correcting writing errors). Parents
      primarily relied on only a couple print (i.e., parent writing the letter alone)
      and graphophonemic (i.e., saying the word as a whole, dictating letters as
      children write) strategies. Graphophonemic and print support in preschool
      predicted children's decoding skills, and graphophonemic support also predicted
      children's future phonological awareness. Neither type of support predicted
      children's vocabulary scores. Demand for precision occurred infrequently and was
      unrelated to children's outcomes. Findings demonstrate the importance of parental
      writing support for augmenting children's literacy skills.

PMID- 25045187
TI  - Discovery of the lomaiviticin biosynthetic gene cluster in Salinispora pacifica.
AB  - The lomaiviticins are a family of cytotoxic marine natural products that have
      captured the attention of both synthetic and biological chemists due to their
      intricate molecular scaffolds and potent biological activities. Here we describe
      the identification of the gene cluster responsible for lomaiviticin biosynthesis
      in Salinispora pacifica strains DPJ-0016 and DPJ-0019 using a combination of
      molecular approaches and genome sequencing. The link between the lom gene cluster
      and lomaiviticin production was confirmed using bacterial genetics, and
      subsequent analysis and annotation of this cluster revealed the biosynthetic
      basis for the core polyketide scaffold. Additionally, we have used comparative
      genomics to identify candidate enzymes for several unusual tailoring events,
      including diazo formation and oxidative dimerization. These findings will allow
      further elucidation of the biosynthetic logic of lomaiviticin assembly and
      provide useful molecular tools for application in biocatalysis and synthetic
      biology.

PMID- 25045189
TI  - Bio-Based Bisfuran: Synthesis, Crystal Structure and Low Molecular Weight
      Amorphous Polyester.
AB  - Discovery of renewable monomer feedstocks for fabrication of polymeric demand is
      critical in achieving sustainable materials. In the present work we have
      synthesized bisfuran diol (BFD) monomer from furfural, over four steps. BFD was
      examined via X-ray crystallography to understand the molecular arrangement in
      space, hydrogen bonding and packing of the molecules. This data was further used
      to compare BFD with structurally related Bisphenol A (BPA), and its known
      derivatives to predict the potential estrogenic or anti-estrogenic activities in
      BFD. Further, BFD was reacted with succinic acid to generate polyester material,
      bisfuran polyester (BFPE-1). MALDI characterization of BFPE-1 indicates low
      molecular weight polyester and thermal analysis reveals amorphous nature of the
      material.

PMID- 25045188
TI  - A broadly applicable and practical oligomeric (salen) Co catalyst for
      enantioselective epoxide ring-opening reactions.
AB  - The (salen) Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in
      a short, chromatography-free synthesis from inexpensive, commercially available
      precursors. This catalyst displays remarkable enhancements in reactivity and
      enantioselectivity relative to monomeric and other multimeric (salen) Co
      catalysts in a wide variety of enantioselective epoxide ring-opening reactions.
      The application of catalyst 4a is illustrated in the kinetic resolution of
      terminal epoxides by nucleophilic ring-opening with water, phenols, and primary
      alcohols; the desymmetrization of meso epoxides by addition of water and
      carbamates; and the desymmetrization of oxetanes by intramolecular ring opening
      with alcohols and phenols. The favorable solubility properties of complex 4a
      under the catalytic conditions facilitated mechanistic studies, allowing
      elucidation of the basis for the beneficial effect of oligomerization. Finally, a
      catalyst selection guide is provided to delineate the specific advantages of
      oligomeric catalyst 4a relative to (salen) Co monomer 1 for each reaction class.

PMID- 25045191
TI  - An "Imperfect" Contraceptive Society: Fertility and Contraception in Italy.
AB  - Italy represents an unexpected and in some ways paradoxical outcome in terms of
      fertility control: a drop to one of the lowest birth rates in the world has been
      accompanied by the preponderant use of "traditional" methods despite the
      availability of "modern" contraception. Using data from 349 interviews conducted
      in 2005-2006 in four Italian cities, we argue that Italian women achieve
      "unplanned" AND desired conceptions through the use of withdrawal and natural
      methods. While data from other countries reveal similar notions of ambivalence
      surrounding pregnancy intentions and contraceptive use, Italy stands out for the
      surprising correlation between highly "managing" the conditions under which
      children are born and the socially commended approach of "letting births happen".
      Such results suggest the need to rethink theoretical understandings of low
      fertility. Through the use of non-technological methods individuals manipulate
      culturally produced norms and beliefs about the appropriate moment to have a
      child; simultaneously, their actions are embedded in larger cultural, economic,
      and political processes.

PMID- 25045190
TI  - Modeling the specificity of protein-DNA interactions.
AB  - The specificity of protein-DNA interactions is most commonly modeled using
      position weight matrices (PWMs). First introduced in 1982, they have been adapted
      to many new types of data and many different approaches have been developed to
      determine the parameters of the PWM. New high-throughput technologies provide a
      large amount of data rapidly and offer an unprecedented opportunity to determine
      accurately the specificities of many transcription factors (TFs). But taking full
      advantage of the new data requires advanced algorithms that take into account the
      biophysical processes involved in generating the data. The new large datasets can
      also aid in determining when the PWM model is inadequate and must be extended to
      provide accurate predictions of binding sites. This article provides a general
      mathematical description of a PWM and how it is used to score potential binding
      sites, a brief history of the approaches that have been developed and the types
      of data that are used with an emphasis on algorithms that we have developed for
      analyzing high-throughput datasets from several new technologies. It also
      describes extensions that can be added when the simple PWM model is inadequate
      and further enhancements that may be necessary. It briefly describes some
      applications of PWMs in the discovery and modeling of in vivo regulatory
      networks.

PMID- 25045192
TI  - A support network typology for application in older populations with a
      preponderance of multigenerational households.
AB  - This paper considers the support networks of older people in populations with a
      preponderance of multigenerational households and examines the most vulnerable
      network types in terms of loneliness and isolation. Current common typologies of
      support networks may not be sensitive to differences within and between different
      cultures. This paper uses cross-sectional data drawn from 590 elders (Gujaratis,
      Punjabis and Sylhetis) living in the United Kingdom and South Asia. Six variables
      were used in K-means cluster analysis to establish a new network typology. Two
      logistic regression models using loneliness and isolation as dependent variables
      assessed the contribution of the new network type to wellbeing. Four support
      networks were identified: 'Multigenerational Households: Older Integrated
      Networks', 'Multigenerational Households: Younger Family Networks', 'Family and
      Friends Integrated Networks' and 'Non-kin Restricted Networks'. Older South
      Asians with 'Non-kin Restricted Networks' were more likely to be lonely and
      isolated compared to others. Using network typologies developed with
      individualistically oriented cultures, distributions are skewed towards more
      robust network types and could underestimate the support needs of older people
      from familistic cultures, who may be isolated and lonely and with limited
      informal sources of help. The new typology identifies different network types
      within multigenerational households, identifies a greater proportion of older
      people with vulnerable networks and could positively contribute to service
      planning.

PMID- 25045193
TI  - Modeling Selective Local Interactions with Memory: Motion on a 2D Lattice.
AB  - We consider a system of particles that simultaneously move on a two-dimensional
      periodic lattice at discrete times steps. Particles remember their last direction
      of movement and may either choose to continue moving in this direction, remain
      stationary, or move toward one of their neighbors. The form of motion is chosen
      based on predetermined stationary probabilities. Simulations of this model reveal
      a connection between these probabilities and the emerging patterns and size of
      aggregates. In addition, we develop a reaction diffusion master equation from
      which we derive a system of ODEs describing the dynamics of the particles on the
      lattice. Simulations demonstrate that solutions of the ODEs may replicate the
      aggregation patterns produced by the stochastic particle model. We investigate
      conditions on the parameters that influence the locations at which particles
      prefer to aggregate. This work is a two-dimensional generalization of [Galante &
      Levy, Physica D, http://dx.doi.org/10.1016/j.physd.2012.10.010], in which the
      corresponding one-dimensional problem was studied.

PMID- 25045194
TI  - NONDRINKER MORTALITY RISK IN THE UNITED STATES.
AB  - The literature has shown that people who do not drink alcohol are at greater risk
      for death than light to moderate drinkers, yet the reasons for this remain
      largely unexplained. We examine whether variation in people's reasons for
      nondrinking explains the increased mortality. Our data come from the 1988-2006
      National Health Interview Survey Linked Mortality File (N= 41,076 individuals age
      21 and above, of whom 10,421 died over the follow-up period). The results
      indicate that nondrinkers include several different groups that have unique
      mortality risks. Among abstainers and light drinkers the risk of mortality is the
      same as light drinkers for a subgroup who report that they do not drink because
      of their family upbringing, and moral/religious reasons. In contrast, the risk of
      mortality is higher than light drinkers for former drinkers who cite health
      problems or who report problematic drinking behaviors. Our findings address a
      notable gap in the literature and may inform social policies to reduce or prevent
      alcohol abuse, increase health, and lengthen life.

PMID- 25045195
TI  - Manifold Learning by Preserving Distance Orders.
AB  - Nonlinear dimensionality reduction is essential for the analysis and the
      interpretation of high dimensional data sets. In this manuscript, we propose a
      distance order preserving manifold learning algorithm that extends the basic mean
      squared error cost function used mainly in multidimensional scaling (MDS)-based
      methods. We develop a constrained optimization problem by assuming explicit
      constraints on the order of distances in the low-dimensional space. In this
      optimization problem, as a generalization of MDS, instead of forcing a linear
      relationship between the distances in the high-dimensional original and low
      dimensional projection space, we learn a non-decreasing relation approximated by
      radial basis functions. We compare the proposed method with existing manifold
      learning algorithms using synthetic datasets based on the commonly used residual
      variance and proposed percentage of violated distance orders metrics. We also
      perform experiments on a retinal image dataset used in Retinopathy of Prematurity
      (ROP) diagnosis.

PMID- 25045196
TI  - Capturing Age-group Differences and Developmental Change with the BASC Parent
      Rating Scales.
AB  - Estimation of age-group differences and intra-individual change across distinct
      developmental periods is often challenged by the use of age-appropriate (but non
      parallel) measures. We present a short version of the Behavior Assessment System
      (Reynolds & Kamphaus, 1998), Parent Rating Scales for Children (PRS-C) and
      Adolescents (PRS-A), which uses only their common-items to derive estimates of
      the initial constructs optimized for developmental studies. Measurement
      invariance of a three-factor model (Externalizing, Internalizing, Adaptive
      Skills) was tested across age-groups (161 mothers using PRS-C; 200 mothers using
      PRS-A) and over time (115 mothers using PRS-C at baseline and PRS-A five years
      later) with the original versus short PRS. Results indicated that the short PRS
      holds a sufficient level of invariance for a robust estimation of age-group
      differences and intra-individual change, as compared to the original PRS, which
      held only weak invariance leading to flawed developmental inferences. Importance
      of test-content parallelism for developmental studies is discussed.

PMID- 25045197
TI  - Immunophenotypes and immune markers associated with acute promyelocytic leukemia
      prognosis.
AB  - CD2+, CD34+, and CD56+ immunophenotypes are associated with poor prognoses of
      acute promyelocytic leukemia (APL). The present study aimed to explore the role
      of APL immunophenotypes and immune markers as prognostic predictors on clinical
      outcomes. A total of 132 patients with de novo APL were retrospectively analyzed.
      Immunophenotypes were determined by flow cytometry. Clinical features, complete
      remission (CR), relapse, and five-year overall survival (OS) rate were assessed
      and subjected to multivariate analyses. The CD13+CD33+HLA-DR-CD34-
      immunophenotype was commonly observed in patients with APL. Positive rates for
      other APL immune markers including cMPO, CD117, CD64, and CD9 were 68.7%, 26%,
      78.4%, and 96.6%, respectively. When compared with patients with CD2- APL,
      patients with CD2+ APL had a significantly higher incidence of early death (50%
      versus 15.7%; P = 0.016), lower CR rate (50% versus 91.1%; P = 0.042), and lower
      five-year OS rate (41.7% versus 74.2%; P = 0.018). White blood cell (WBC) count
      before treatment was found to be the only independent risk factor of early death,
      CR failure, and five-year mortality rate. Flow cytometric immunophenotype
      analysis can facilitate prompt APL diagnosis. Multivariate analysis has
      demonstrated that WBC count before treatment is the only known independent risk
      factor that predicts prognosis for APL in this study population. 

PMID- 25045199
TI  - Design and Laboratory Evaluation of a Sequential Spot Sampler for Time-Resolved
      Measurement of Airborne Particle Composition.
AB  - A new sampling approach has been developed to enable affordable, time-resolved
      monitoring of particulate chemical compositions, and more generally to provide
      concentrated samples of airborne particles. Using a newly developed, moderated
      water-based condensational growth technology, individual particle samples are
      deposited in a 1-mm diameter dry "spot". The moderated condensation technology
      enables this collection with minimal temperature rise, providing robust
      collection for volatile constituents. Measured collection efficiencies are above
      95% for particles in the size range from 0.010 MUm to 2.5 MUm. A set of 20 or
      more time-resolved samples, plus blanks, may be collected onto a multiwell
      collection plate. For chemical analysis the plate is returned to the laboratory,
      and placed directly into a modified autosampler, without extraction or
      preparation. The autosampler handles the addition of eluent, extraction, and
      sample injection without user manipulation. This paper presents the design and
      laboratory evaluation of a 1.5 L/min sampling rate version of this system.

PMID- 25045200
TI  - The Relationship Between Social Support and Subjective Well-Being Across Age.
AB  - The relationships among types of social support and different facets of
      subjective well-being (i.e., life satisfaction, positive affect, and negative
      affect) were examined in a sample of 1,111 individuals between the ages of 18 and
      95. Using structural equation modeling we found that life satisfaction was
      predicted by enacted and perceived support, positive affect was predicted by
      family embeddedness and provided support, and negative affect was predicted by
      perceived support. When personality variables were included in a subsequent
      model, the influence of the social support variables were generally reduced.
      Invariance analyses conducted across age groups indicated that there were no
      substantial differences in predictors of the different types of subjective well
      being across age.

PMID- 25045198
TI  - Clinical usefulness of novel serum and imaging biomarkers in risk stratification
      of patients with stable angina.
AB  - Inflammatory mediators appear to be the most intriguing yet confusing subject,
      regarding the management of patients with acute coronary syndromes (ACS). The
      current inflammatory concept of atherosclerotic coronary artery disease (CAD) led
      many investigators to concentrate on systemic markers of inflammation, as well as
      imaging techniques, which may be helpful in risk stratification and prognosis
      assessment for cardiovascular events. In this review, we try to depict many of
      the recently studied markers regarding stable angina (SA), their clinical
      usefulness, and possible future applications in the field. 

PMID- 25045203
TI  - An acousto-optic sensor based on resonance grating waveguide structure.
AB  - This paper presents an acousto-optic (AO) sensor based on resonance grating
      waveguide structure. The sensor is fabricated using elastic polymer materials to
      achieve a good sensitivity to ultrasound pressure waves. Ultrasound pressure
      waves modify the structural parameters of the sensor and result in the optical
      resonance shift of the sensor. This converts into a light intensity modulation. A
      commercial ultrasound transducer at 20 MHz is used to characterize a fabricated
      sensor and detection sensitivity at different optical source wavelength within a
      resonance spectrum is investigated. Practical use of the sensor at a fixed
      optical source wavelength is presented. Ultimately, the geometry of the planar
      sensor structure is suitable for two-dimensional, optical pressure imaging
      applications such as pressure wave detection and mapping, and ultrasound imaging.

PMID- 25045201
TI  - Costs of reproduction in a long-lived female primate: injury risk and wound
      healing.
AB  - Reproduction is a notoriously costly phase of life, exposing individuals to
      injury, infectious disease, and energetic tradeoffs. The strength of these costs
      should be influenced by life history strategies, and in long-lived species,
      females may be selected to mitigate costs of reproduction because life span is
      such an important component of their reproductive success. Here we report
      evidence for two costs of reproduction that may influence survival in wild female
      baboons-injury risk and delayed wound healing. Based on 29 years of observations
      in the Amboseli ecosystem, Kenya, we found that wild female baboons experienced
      the highest risk of injury on days when they were most likely to be ovulating. In
      addition, lactating females healed from wounds more slowly than pregnant or
      cycling females, indicating a possible tradeoff between lactation and immune
      function. We also found variation in injury risk and wound healing with dominance
      rank and age: older and low-status females were more likely to be injured than
      younger or high-status females, and older females exhibited slower healing than
      younger females. Our results support the idea that wild non-human primates
      experience energetic and immune costs of reproduction, and they help illuminate
      life history tradeoffs in long-lived species.

PMID- 25045202
TI  - Cognitive and Clinical Characteristics of Sexual and Religious Obsessions.
AB  - Sexual and religious obsessions are often grouped together as unacceptable
      thoughts, symptoms of obsessive-compulsive disorder hypothesized to be maintained
      by maladaptive beliefs about the importance and control of thoughts. Although
      there is empirical justification for this typology, there are several reasons to
      suspect that sexual and religious obsessions may differ with respect to
      associated obsessional beliefs and personality traits. In this study, we examined
      the associations between sexual and religious obsessions (separately) and (a)
      putatively obsessional cognitive styles, especially beliefs about the importance
      and control of thoughts, and responsibility, (b) obsessive-compulsive personality
      traits, and (c) schizotypal personality traits. Whereas sexual obsessions were
      predicted only by increased beliefs about the importance and control of thoughts,
      and contamination obsessions were predicted only by inflated responsibility
      appraisals and threat estimation, religious obsessions were independently
      predicted by both of these constructs. In addition, only religious obsessions
      were related to self-reported obsessive-compulsive personality traits.
      Researchers and clinicians should be cognizant of potentially important
      distinctions between sexual and religious obsessions, and the possibility that
      scrupulous OCD shares processes with both autogenous and reactive presentations.

PMID- 25045204
TI  - Understanding Excitation Energy Transfer in Metalloporphyrin Heterodimers with
      Different Linkers, Bonding Structures and Geometries through Stimulated X-Ray
      Raman Spectroscopy.
AB  - We present simulations of stimulated X-ray Raman (SXRS) signals from covalent
      porphyrin heterodimers with different linkers, chemical bonding structures and
      geometries. The signals are interpreted in terms of valence electron wavepacket
      motion. One- and two-color SXRS signals can jointly indicate excitation energy
      transfer (EET) between the porphyrin monomers. It is shown that the SXRS signals
      provide a novel window into EET dynamics in multiporphyrin systems, and can be
      used as a powerful tool to monitor the subtle chemical environment which affects
      EET.

PMID- 25045205
TI  - Dispersion of a Nanoliter Bolus in Microfluidic Co-Flow.
AB  - Microfluidic systems enable reactions and assays on the scale of nanoliters.
      However, at this scale nonuniformities in sample delivery become significant. To
      determine the fundamental minimum sample volume required for a particular device,
      a detailed understanding of mass transport is required. Co-flowing laminar
      streams are widely used in many devices, but typically only in the steady-state.
      Because establishing the co-flow steady-state consumes excess sample volume and
      time, there is a benefit to operating devices in the transient state, which
      predominates as the volume of the co-flow reactor decreases. Analysis of the co
      flow transient has been neglected thus far. In this work we describe the
      fabrication of a pneumatically controlled microfluidic injector constructed to
      inject a discrete 50nL bolus into one side of a two-stream co-flow reactor. Using
      dye for image analysis, injections were performed at a range of flow rates from
      0.5-10MUL/min, and for comparison we collected the co-flow steady-state data for
      this range. The results of the image analysis were also compared against theory
      and simulations for device validation. For evaluation, we established a metric
      that indicates how well the mass distribution in the bolus injection approximates
      steady-state co-flow. Using such analysis, transient-state injections can
      approximate steady-state conditions within predefined errors, allowing straight
      forward measurements to be performed with reduced reagent consumption.

PMID- 25045206
TI  - Decreased expression of the aryl hydrocarbon receptor in ocular Behcet's disease.
AB  - Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in
      immune responses. AhR is activated following interaction with its ligands, such
      as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole
      4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of
      AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's
      disease (BD). The expression of AhR was significantly decreased in active BD
      patients as compared to inactive BD patients and normal controls. Both FICZ and
      ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by
      PBMCs and by CD4(+)T cells in active BD patients and normal controls. Stimulation
      of purified CD4(+)T cells with FICZ or ITE caused a decreased expression of RORC,
      IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The
      present study suggests that a decreased AhR expression is associated with disease
      activity in BD patients. The activation of AhR by either FICZ or ITE was able to
      inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate
      whether modulation of AhR might be used in the treatment of BD. 

PMID- 25045207
TI  - Role of training and detraining on inflammatory and metabolic profile in
      infarcted rats: influences of cardiovascular autonomic nervous system.
AB  - The aim of this study was to evaluate the effects of exercise training (ET, 50
      70% of VO2 max, 5 days/week) and detraining (DT) on inflammatory and metabolic
      profile after myocardial infarction (MI) in rats. Male Wistar rats were divided
      into control (C, n = 8), sedentary infarcted (SI, n = 9), trained infarcted (TI,
      n = 10; 3 months of ET), and detrained infarcted (DI, n = 11; 2 months of ET + 1
      month of DT). After ET and DT protocols, ventricular function and inflammation,
      cardiovascular autonomic modulation (spectral analysis), and adipose tissue
      inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac
      and vascular autonomic modulation, and these benefits were correlated with
      reduced inflammatory cytokines on the heart and adipose tissue. These positive
      changes were sustained even after 1 month of detraining. No expressive changes
      were observed in oxidative stress and lipolytic pathway in experimental groups.
      In conclusion, our results strongly suggest that the autonomic improvement
      promoted by ET, and maintained even after the detraining period, was associated
      with reduced inflammatory profile in the left ventricle and adipose tissue of
      rats subjected to MI. These data encourage enhancing cardiovascular autonomic
      function as a therapeutic strategy for the treatment of inflammatory process
      triggered by MI.

PMID- 25045208
TI  - Boehmeria nivea attenuates the development of dextran sulfate sodium-induced
      experimental colitis.
AB  - We examined the therapeutic effect of an ethanol extract derived from Boehmeria
      nivea (Linn.) Gaudich in a mouse model of experimental colitis. Treatment with
      70% ethanol extract derived from B. nivea (EBN) at a dose of 100, 200, or 500
      mg/(kg . d) improved colon shortening, body weight, the disease activity index
      (DAI), and histopathological score of DSS-induced colitis mice. DSS significantly
      increased the levels of cyclooxygenase-(COX-) 2 in colon tissue relative to that
      of the untreated control group. EBN administered at 100, 200, or 500 mg/(kg . d)
      reduced COX-2 levels in the DSS-treated mice. In addition, EBN decreased the DSS
      induced secretion of the inflammatory cytokine interleukin-6 (IL-6) and chemokine
      monocyte chemotactic protein-1 (MCP-1). Taken together, these data suggest that
      B. nivea extract is effective in preventing colitis.

PMID- 25045209
TI  - Functional roles of Syk in macrophage-mediated inflammatory responses.
AB  - Inflammation is a series of complex biological responses to protect the host from
      pathogen invasion. Chronic inflammation is considered a major cause of diseases,
      such as various types of inflammatory/autoimmune diseases and cancers. Spleen
      tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic
      cells and has been known to play crucial roles in adaptive immune responses.
      However, recent studies have reported that Syk is also involved in other
      biological functions, especially in innate immune responses. Although Syk has
      been extensively studied in adaptive immune responses, numerous studies have
      recently presented evidence that Syk has critical functions in macrophage
      mediated inflammatory responses and is closely related to innate immune response.
      This review describes the characteristics of Syk-mediated signaling pathways,
      summarizes the recent findings supporting the crucial roles of Syk in macrophage
      mediated inflammatory responses and diseases, and discusses Syk-targeted drug
      development for the therapy of inflammatory diseases. 

PMID- 25045211
TI  - Aspirin modulates innate inflammatory response and inhibits the entry of
      Trypanosoma cruzi in mouse peritoneal macrophages.
AB  - The intracellular protozoan parasite Trypanosoma cruzi causes Chagas disease, a
      serious disorder that affects millions of people in Latin America. Cell invasion
      by T. cruzi and its intracellular replication are essential to the parasite's
      life cycle and for the development of Chagas disease. Here, we present evidence
      suggesting the involvement of the host's cyclooxygenase (COX) enzyme during T.
      cruzi invasion. Pharmacological antagonist for COX-1, aspirin (ASA), caused
      marked inhibition of T. cruzi infection when peritoneal macrophages were
      pretreated with ASA for 30 min at 37 degrees C before inoculation. This
      inhibition was associated with increased production of IL-1beta and nitric oxide
      (NO(?)) by macrophages. The treatment of macrophages with either NOS inhibitors
      or prostaglandin E2 (PGE2) restored the invasive action of T. cruzi in
      macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2
      reversed the inhibitory effect of ASA on trypomastigote invasion. Our results
      indicate that PGE2, NO(?), and lipoxins are involved in the regulation of anti-T.
      cruzi activity by macrophages, providing a better understanding of the role of
      prostaglandins in innate inflammatory response to T. cruzi infection as well as
      adding a new perspective to specific immune interventions.

PMID- 25045210
TI  - Tumour necrosis factor superfamily members in the pathogenesis of inflammatory
      bowel disease.
AB  - Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the
      gastrointestinal tract of unclear aetiology of which two major forms are Crohn's
      disease (CD) and ulcerative colitis (UC). CD and UC are immunologically distinct,
      although they both result from hyperactivation of proinflammatory pathways in
      intestines and disruption of intestinal epithelial barrier. Members of the tumour
      necrosis factor superfamily (TNFSF) are molecules of broad spectrum of activity,
      including direct disruption of intestinal epithelial barrier integrity and
      costimulation of proinflammatory functions of lymphocytes. Tumour necrosis factor
      (TNF) has a well-established pathological role in IBD which also serves as a
      target in IBD treatment. In this review we discuss the role of TNF and other
      TNFSF members, notably, TL1A, FasL, LIGHT, TRAIL, and TWEAK, in the pathogenesis
      of IBD. 

PMID- 25045212
TI  - Role of exercise training on autonomic changes and inflammatory profile induced
      by myocardial infarction.
AB  - The cardiovascular autonomic imbalance in patients after myocardial infarction
      (MI) provides a significant increase in mortality rate, and seems to precede
      metabolic, hormonal, and immunological changes. Moreover, the reduction in the
      parasympathetic function has been associated with inflammatory response in
      different pathological conditions. Over the years, most of the studies have
      indicated the exercise training (ET) as an important nonpharmacological tool in
      the management of autonomic dysfunction and reduction in inflammatory profile
      after a myocardial infarction. In this work, we reviewed the effects of ET on
      autonomic imbalance after MI, and its consequences, particularly, in the post-MI
      inflammatory profile. Clinical and experimental evidence regarding relationship
      between alterations in autonomic regulation and local or systemic inflammation
      response after MI were also discussed. 

PMID- 25045213
TI  - Anti-inflammatory effects of IKK inhibitor XII, thymulin, and fat-soluble
      antioxidants in LPS-treated mice.
AB  - The present study was designed to compare the anti-inflammatory effects of
      several agents applied in vivo, namely, a synthetic inhibitor of the NF-kappaB
      cascade, fat-soluble antioxidants, and the thymic peptide thymulin. Cytokine
      response in LPS-treated mice was analysed in tandem with the following
      parameters: the synthesis of inducible forms of the heat shock proteins HSP72 and
      HSP90alpha; activity of the NF-kappaB and SAPK/JNK signalling pathways; and TLR4
      expression. Inflammation-bearing Balb/c male mice were pretreated with an
      inhibitor of IKK-alpha/beta kinases (IKK Inhibitor XII); with thymulin; with
      dietary coenzyme Q9, alpha-tocopherol, and beta-carotene; or with combinations of
      the inhibitor and peptide or antioxidants. Comparable anti-inflammatory effects
      were observed in inflammation-bearing mice treated separately with thymulin or
      with dietary antioxidants administered daily for two weeks before LPS treatment.
      When LPS-injected mice were treated with the inhibitor and antioxidants together,
      neither plasma cytokines, signal proteins, nor heat shock proteins recovered more
      efficiently than when mice were treated with these agents separately. In contrast
      to antioxidant diet, the thymulin was shown to increase the effect of IKK
      Inhibitor XII in preventing IKK activation in LPS-treated mice. 

PMID- 25045215
TI  - When legal rights are not a reality: do individuals know their rights and how can
      we tell?
AB  - Public knowledge of rights has been the subject of a number of empirical
      enquiries over the last decade. In England and Wales, knowledge of rights and its
      relationship with an individual's capacity to 'self-help' and 'self-represent'
      when faced with a civil justice problem has become the subject of renewed
      attention following changes to legal aid which, from March 2013, will see the
      availability of legal advice and representation dramatically reduced. Previous
      studies focusing on public knowledge of rights in this (and other) jurisdictions
      have illustrated a lack of knowledge amongst the general population and more
      specifically, a widespread tendency of individuals to assume that the law aligns
      with their own moral, ethical or social attitudes. However, many of these studies
      have also suffered from methodological shortcomings. In attempting to address
      some of these shortcomings this study uses an open-ended format to ask
      individuals with one or one or more civil or social justice problems to describe
      their rights/legal position. We find that whilst an open-ended question approach
      to exploring knowledge of rights yields insight not acquired by other formats,
      its utility is constrained by difficulty reconciling articulation and actual
      knowledge of rights. We discuss the implications of these findings as they relate
      to the development of future research in the field of family and social welfare
      law, Public Legal Education (PLE) and access to justice post-March 2013.

PMID- 25045214
TI  - Rapamycin attenuated cardiac hypertrophy induced by isoproterenol and maintained
      energy homeostasis via inhibiting NF-kappaB activation.
AB  - Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent
      rejection organ (especially kidney) transplantation. However, little is known
      about the role of Rapa in cardiac hypertrophy induced by isoproterenol and its
      underlying mechanism. In this study, Rapa was administrated intraperitoneally for
      one week after the rat model of cardiac hypertrophy induced by isoproterenol
      established. Rapa was demonstrated to attenuate isoproterenol-induced cardiac
      hypertrophy, maintain the structure integrity and functional performance of
      mitochondria, and upregulate genes related to fatty acid metabolism in
      hypertrophied hearts. To further study the implication of NF-kappaB in the
      protective role of Rapa, cardiomyocytes were pretreated with TNF-alpha or
      transfected with siRNA against NF-kappaB/p65 subunit. It was revealed that the
      upregulation of extracellular circulating proinflammatory cytokines induced by
      isoproterenol was able to be reversed by Rapa, which was dependent on NF-kappaB
      pathway. Furthermore, the regression of cardiac hypertrophy and maintaining
      energy homeostasis by Rapa in cardiomyocytes may be attributed to the
      inactivation of NF-kappaB. Our results shed new light on mechanisms underlying
      the protective role of Rapa against cardiac hypertrophy induced by isoproterenol,
      suggesting that blocking proinflammatory response by Rapa might contribute to the
      maintenance of energy homeostasis during the progression of cardiac hypertrophy. 

PMID- 25045216
TI  - INVERSE STABLE SUBORDINATORS.
AB  - The inverse stable subordinator provides a probability model for time-fractional
      differential equations, and leads to explicit solution formulae. This paper
      reviews properties of the inverse stable subordinator, and applications to a
      variety of problems in mathematics and physics. Several different governing
      equations for the inverse stable subordinator have been proposed in the
      literature. This paper also shows how these equations can be reconciled.

PMID- 25045217
TI  - Large Scale Chemical Cross-linking Mass Spectrometry Perspectives.
AB  - The spectacular heterogeneity of a complex protein mixture from biological
      samples becomes even more difficult to tackle when one's attention is shifted
      towards different protein complex topologies, transient interactions, or
      localization of PPIs. Meticulous protein-by-protein affinity pull-downs and yeast
      two-hybrid screens are the two approaches currently used to decipher proteome
      wide interaction networks. Another method is to employ chemical cross-linking,
      which gives not only identities of interactors, but could also provide
      information on the sites of interactions and interaction interfaces. Despite
      significant advances in mass spectrometry instrumentation over the last decade,
      mapping Protein-Protein Interactions (PPIs) using chemical cross-linking remains
      time consuming and requires substantial expertise, even in the simplest of
      systems. While robust methodologies and software exist for the analysis of binary
      PPIs and also for the single protein structure refinement using cross-linking
      derived constraints, undertaking a proteome-wide cross-linking study is highly
      complex. Difficulties include i) identifying cross-linkers of the right length
      and selectivity that could capture interactions of interest; ii) enrichment of
      the cross-linked species; iii) identification and validation of the cross-linked
      peptides and cross-linked sites. In this review we examine existing literature
      aimed at the large-scale protein cross-linking and discuss possible paths for
      improvement. We also discuss short-length cross-linkers of broad specificity such
      as formaldehyde and diazirine-based photo-cross-linkers. These cross-linkers
      could potentially capture many types of interactions, without strict requirement
      for a particular amino-acid to be present at a given protein-protein interface.
      How these shortlength, broad specificity cross-linkers be applied to proteome
      wide studies? We will suggest specific advances in methodology, instrumentation
      and software that are needed to make such a leap.

PMID- 25045218
TI  - Increasing burden of Alzheimer's disease by aging.

PMID- 25045219
TI  - Primary prevention of Alzheimer's disease: is it an attainable goal?
AB  - Alzheimer's disease (AD) is the leading cause of dementia, and the most prevalent
      neurodegenerative disease in the elderly. The prevalence of AD is predicted to
      rise as life expectancy grows across populations. The exact cause of this
      devastating disease is still unknown; however, it is an aging-related multi
      factorial disorder, and growing evidence supports the contribution of modifiable
      environmental factors to unmodifiable factors such as gene and ageing itself. The
      recent advancement of methodologies and techniques for early diagnosis of AD
      facilitates the investigation of strategies to reduce the risk for AD progression
      in the earliest stages of the disease. Pharmacological attempts at curing,
      halting or modifying it have, by and large, been unsuccessful, and no
      breakthrough is seen in the near future. However, a lot of elements that seem to
      contribute to the disease such as risk factors have been identified, mainly from
      epidemiological and basic research studies. Many of these are amenable to
      lifestyle modification. Therefore, prevention in the preclinical stage is likely
      the most effective way to decrease the incidence of this age-associated dreadful
      neurodegenerative condition, and its associated burden for individuals and
      society. We provide an overview of modifiable risk factors for AD along with the
      supporting evidence. 

PMID- 25045221
TI  - Prevalence and trends of dementia in Korea: a systematic review and meta
      analysis.
AB  - Through a systematic review and meta-analysis of epidemiological studies on
      dementia, we assessed the prevalence of dementia and its subtypes-Alzheimer'
      disease (AD) and vascular dementia (VaD)-in Korea. We searched for
      epidemiological studies on dementia published in 1990-2013 using PubMed, Scopus,
      EMBASE, KoreaMed, KISS, and RiCH. Dementia prevalence in elderly patients
      (aged>=65 yr) was 9.2% (95% confidence interval [CI], 8.2%-10.4%) from 11
      studies, which was higher than those from Western and other Asian countries. AD
      was the most prevalent dementia type, with a prevalence of 5.7% (95% CI, 5.0%
      6.4%) from 10 studies compared with 2.1% (95% CI, 1.6%-2.7%) for VaD from 9
      studies. The age-specific prevalence of dementia approximately doubled with each
      5.8-yr increase of age. Although a significant increasing trend of dementia
      prevalence was not observed, it increased slightly from 7.3% to 8.7% after 2005;
      AD prevalence increased after 1995 and VaD prevalence decreased after the early
      2000s. The AD/VaD ratio increased from 1.96 in the early 1990s to 4.13 in the
      2010s, similar to the worldwide ratio. Owing to this high prevalence in the aging
      population, dementia will impose significant economic burdens to Korean society. 

PMID- 25045220
TI  - Diverse molecular targets for therapeutic strategies in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia caused by
      neurodegenerative process and is tightly related to amyloid beta (Abeta) and
      neurofibrillary tangles. The lack of early diagnostic biomarker and therapeutic
      remedy hinders the prevention of increasing population of AD patients every year.
      In spite of accumulated scientific information, numerous clinical trials for
      candidate drug targets have failed to be preceded into therapeutic development,
      therefore, AD-related sufferers including patients and caregivers, are desperate
      to seek the solution. Also, effective AD intervention is desperately needed to
      reduce AD-related societal threats to public health. In this review, we summarize
      various drug targets and strategies in recent preclinical studies and clinical
      trials for AD therapy: Allopathic treatment, immunotherapy, Abeta
      production/aggregation modulator, tau-targeting therapy and metabolic targeting.
      Some has already failed in their clinical trials and the others are still in
      various stages of investigations, both of which give us valuable information for
      future research in AD therapeutic development. 

PMID- 25045222
TI  - The recent decline in prevalence of dementia in developed countries: implications
      for prevention in the Republic of Korea.
AB  - With the rapid aging of the population in Korea, the number of older people with
      dementia is projected to increase, forecasting an epidemic of dementia. Recent
      trends in dementia in several western countries, however, depict a gradual
      decline in prevalence and incidence. This decrease has been attributed to an
      improvement in education and living environments, engagement in healthy
      behaviors, and reduction in the prevalence of vascular risk factors. In Korea,
      however, trends in modifiable risk factors do not favor an optimistic outlook due
      to the continuous increase in the prevalence of hypertension, diabetes mellitus,
      and obesity. Given these observations, there is much to be gained through the
      promotion of healthy lifestyles. Moreover, public health resources need to be
      directed toward the provision of health promotion and preventive services,
      control and management of vascular risk factors, and improvement in the standard
      of living. Nationwide initiatives to develop and implement policies and
      strategies to protect cognitive health throughout the lifespan should be
      considered a public health priority. 

PMID- 25045223
TI  - Moving toward universal coverage of health insurance in Vietnam: barriers,
      facilitating factors, and lessons from Korea.
AB  - Vietnam has pursued universal health insurance coverage for two decades but has
      yet to fully achieve this goal. This paper investigates the barriers to achieve
      universal coverage and examines the validity of facilitating factors to shorten
      the transitional period in Vietnam. A comparative study of facilitating factors
      toward universal coverage of Vietnam and Korea reveals significant internal
      forces for Vietnam to further develop the National Health Insurance Program.
      Korea in 1977 and Vietnam in 2009 have common characteristics to be favorable of
      achieving universal coverage with similarities of level of income, highly
      qualified administrative ability, tradition of solidarity, and strong political
      leadership although there are differences in distribution of population and
      structure of the economy. From a comparative perspective, Vietnam can consider
      the experience of Korea in implementing the mandatory enrollment approach,
      household unit of eligibility, design of contribution and benefit scheme, and
      resource allocation to health insurance for sustainable government subsidy to
      achieve and sustain the universal coverage of health insurance. 

PMID- 25045224
TI  - Clinical significance of previously cryptic copy number alterations and loss of
      heterozygosity in pediatric acute myeloid leukemia and myelodysplastic syndrome
      determined using combined array comparative genomic hybridization plus single
      nucleotide polymorphism microarray analyses.
AB  - The combined array comparative genomic hybridization plus single-nucleotide
      polymorphism microarray (CGH+SNP microarray) platform can simultaneously detect
      copy number alterations (CNA) and copy-neutral loss of heterozygosity (LOH).
      Eighteen children with acute myeloid leukemia (AML) (n=15) or myelodysplastic
      syndrome (MDS) (n=3) were studied using CGH+SNP microarray to evaluate the
      clinical significance of submicroscopic chromosomal aberrations. CGH+SNP
      microarray revealed CNAs at 14 regions in 9 patients, while metaphase cytogenetic
      (MC) analysis detected CNAs in 11 regions in 8 patients. Using CGH+SNP
      microarray, LOHs>10 Mb involving terminal regions or the whole chromosome were
      detected in 3 of 18 patients (17%). CGH+SNP microarray revealed cryptic LOHs with
      or without CNAs in 3 of 5 patients with normal karyotypes. CGH+SNP microarray
      detected additional cryptic CNAs (n=2) and LOHs (n=5) in 6 of 13 patients with
      abnormal MC. In total, 9 patients demonstrated additional aberrations, including
      CNAs (n=3) and/or LOHs (n=8). Three of 15 patients with AML and terminal LOH>10
      Mb demonstrated a significantly inferior relapse-free survival rate (P=0.041).
      This study demonstrates that CGH+SNP microarray can simultaneously detect
      previously cryptic CNAs and LOH, which may demonstrate prognostic implications. 

PMID- 25045225
TI  - Imaging mass spectrometry in papillary thyroid carcinoma for the identification
      and validation of biomarker proteins.
AB  - Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption
      ionization and time-of-flight (MALDI-TOF) mass spectrometry has become
      increasingly important in biology and medicine, because this technology can
      detect the relative abundance and spatial distribution of interesting proteins in
      tissues. Five thyroid cancer samples, along with normal tissue, were sliced and
      transferred onto conductive glass slides. After laser scanning by MALDI-TOF
      equipped with a smart beam laser, images were created for individual masses and
      proteins were classified at 200-um spatial resolution. Based on the spatial
      distribution, region-specific proteins on a tumor lesion could be identified by
      protein extraction from tumor tissue and analysis using liquid chromatography
      with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each
      spot, various intensities of a specific peak were detected in the tumor and
      normal regions of the thyroid. Differences in the molecular weights of expressed
      proteins between tumor and normal regions were analyzed using unsupervised and
      supervised clustering. To verify the presence of discovered proteins through IMS,
      we identified ribosomal protein P2, which is specific for cancer. We have
      demonstrated the feasibility of IMS as a useful tool for the analysis of tissue
      sections, and identified the tumor-specific protein ribosomal protein P2. 

PMID- 25045226
TI  - Elevated brachial-ankle pulse wave velocity is independently associated with
      microalbuminuria in a rural population.
AB  - Microalbuminuria is a marker of generalized endothelial dysfunction resulting
      from arterial stiffness or insulin resistance, and brachial-ankle pulse wave
      velocity (baPWV) is a good measure of arterial stiffness. We aimed to investigate
      whether elevated baPWV is independently associated with microalbuminuria. This
      study included 1,648 individuals aged over 40 who participated in the baseline
      Multi-Rural Cohort Study conducted in Korean rural communities between 2005 and
      2006. Participants were classified into less than 30 mg/g as normoalbuminuria or
      30-300 mg/g as microalbuminuriausing urinary albumin creatinine ratio (UACR). The
      median and Q1-Q3 baPWV values were significantly higher in the microalbuminuric
      group both in men (1,538, 1,370-1,777 cm/s vs. 1,776, 1,552-2,027 cm/s, P <
      0.001) and women (1,461, 1,271-1,687 cm/s vs. 1,645, 1,473-1,915 cm/s, P <
      0.001). BaPWV was independently associated with microalbuminuria in both genders
      after adjusting for pulse rate; fasting blood glucose; triglyceride; homeostatic
      model assessment insulin resistance (HOMAIR) and, history of hypertension and
      diabetes. Fasting blood sugar and HOMAIR were judged as having nothing to do with
      multicolinearity (r = 0.532, P < 0.001). Elevated baPWV was independently
      associated with microalbuminuria regardless of insulin resistance among rural
      subjects over 40 yr. 

PMID- 25045227
TI  - Relationship between neutrophil-to-lymphocyte ratio and plaque components in
      patients with coronary artery disease: virtual histology intravascular ultrasound
      analysis.
AB  - The aim of this study was to evaluate the relation between neutrophil-to
      lymphocyte ratio (NLR) and plaque components assessed by virtual histology
      intravascular ultrasound in 399 coronary artery disease (CAD) patients with 471
      coronary lesions. We classified the lesions into two groups according to the NLR
      on admission {low NLR group (NLR<=2.73 [n=370]) vs. high NLR group (NLR>2.73
      [n=101])}. By volumetric analysis, total atheroma and the absolute necrotic core
      (NC) volumes were significantly greater in high NLR group (249.9+/-149.7 uL vs.
      192.5+/-127.7 uL, P=0.001, and 32.7+/-26.8 uL vs. 22.8+/-19.4 uL, P=0.001,
      respectively) and thin-cap fibroatheroma (TCFA) was observed more frequently in
      high NLR group (33% vs. 18%, P=0.001). ST segment elevation myocardial infarction
      (odds ratio [OR], 2.159; 95% CI, 1.000-4.660, P=0.050) and NLR>2.73 (OR, 1.848;
      95% CI, 1.016-3.360, P=0.044) and total atheroma volume (OR, 1.003; 95% CI, 1.001
      1.004, P=0.004) were the independent predictors of TCFA. CAD patients with high
      NLR had more vulnerable plaque components (greater NC-containing plaques) than
      those with low NLR. 

PMID- 25045228
TI  - The clinical association of the blood pressure variability with the target organ
      damage in hypertensive patients with chronic kidney disease.
AB  - It is known that blood pressure variability (BPV) can independently affect target
      organ damage (TOD), even with normal blood pressure. There have been few
      studieson chronic kidney disease (CKD) patients. We evaluated the relationship
      between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD
      patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure
      monitoring. BPV was defined as the average real variability, with a mean value of
      the absolute differences between consecutive readings of systolic blood pressure.
      TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score
      >=4 in electrocardiography) and kidney injury (as determined from an estimated
      glomerular filtration rate [eGFR]<30 mL/min/1.73 m(2) and proteinuria).The mean
      BPV of the subjects was 15.9+/-4.63 mmHg. BPV displayed a positive relationship
      with LVH in a univariate analysis and after adjustment for multi-variables (odds
      ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no
      relationship with kidney injury. These data suggest that BPV may be positively
      associated with LVH in hypertensive CKD patients.

PMID- 25045229
TI  - Association of vitamin B12 deficiency and metformin use in patients with type 2
      diabetes.
AB  - We evaluated the prevalence of vitamin B12 deficiency and associated factors in
      type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients
      using metformin was enrolled. Vitamin B12 and folate levels were quantified by
      chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as
      vitamin B12 <= 300 pg/mL without folate deficiency (folate > 4 ng/mL). The
      prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes
      patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 +/- 246.7
      pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P <
      0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients.
      Compared with daily metformin dose of <= 1,000 mg, the adjusted odds ratio for
      1,000-2,000 mg, and >= 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80
      (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the
      adjusted odds ratios for 4-10 yr, and >= 10 yr were 4.65 (95% CI, 2.36-9.16, P <
      0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our
      study indicates that patients with type 2 diabetes treated with metformin should
      be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg)
      and longer durations (>= 4 yr) of treatment. 

PMID- 25045230
TI  - Clinical significance of non-alcoholic fatty liver disease as a risk factor for
      prehypertension.
AB  - Previous epidemiologic studies have shown the clinical association between non
      alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However,
      there is only limited information about the effect of NAFLD on the development of
      hypertension. Accordingly, we investigated the clinical association between NAFLD
      and prehypertension. A prospective cohort study was conducted on the 11,350
      Korean men without prehypertension for 5 yr. The incidences of prehypertension
      were evaluated, and Cox proportional hazard model was used to measure the hazard
      ratios (HRs) for the development of prehypertension according to the degree of
      NAFLD (normal, mild, moderate to severe). The incidence of prehypertension
      increased according to NAFLD states (normal: 55.5%, mild: 63.7%, moderate to
      severe: 70.3%, P<0.001). Even after adjusting for multiple covariates, the HRs
      (95% confidence interval) for prehypertension were higher in the mild group
      (1.18; 1.07-1.31) and moderate to severe group (1.62; 1.21-2.17), compared to
      normal group, respectively (P for trend <0.001). The development of
      prehypertension is more potentially associated with the more progressive NAFLD
      than normal and milder state. These findings suggest the clinical significance of
      NAFLD as one of risk factors for prehypertension. 

PMID- 25045231
TI  - Toxicity profile of temozolomide in the treatment of 300 malignant glioma
      patients in Korea.
AB  - This study evaluated the toxicity profiles of temozolomide in the treatment of
      malignant glioma as either concurrent or adjuvant chemotherapy. We
      retrospectively reviewed the medical records of 300 malignant glioma patients
      treated with temozolomide in two medical institutions in Korea between 2004 and
      2010. Two hundred nine patients experienced a total of 618 toxicities during
      temozolomide therapy. A total of 84.8% of the 618 toxicities were Common
      Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were
      grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia
      (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic
      toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three
      most common toxicities. There was no mortality due to temozolomide. Although
      temozolomide showed many types of toxicities, the majority of the toxicities were
      tolerable and of lower grade. Gastrointestinal troubles are the most common
      toxicities in Korean patients treated with temozolomide. 

PMID- 25045232
TI  - Comparison of epidemiology, emergency care, and outcomes of acute ischemic stroke
      between young adults and elderly in Korean population: a multicenter
      observational study.
AB  - Stroke in young adults has been known to show a lower incidence and a better
      prognosis. Only a few studies have examined the epidemiology and outcomes of
      ischemic stroke in young adults and compared them with the elderly in Korean
      population. All consecutive patients with ischemic stroke visiting 29
      participating emergency departments were enrolled from November 2007 to October
      2009. Patients with less than 15 yr of age and unknown information on age and
      confirmed diagnosis were excluded. We categorized the patients into young adults
      (15 to 45 yr) and elderly (46 yr and older) groups. Of 39,156 enrolled all stroke
      patients, 25,818 with ischemic stroke were included and analyzed (young adult;
      n=1,431, 5.5%). Young adult patients showed lower prevalence of most chronic
      diseases but significantly higher prevalence in exercise, current smoking, and
      alcohol consumption. Hospital mortality was significantly lower in young adults
      than elderly (1.1% vs. 3.1%, P<0.001). Higher number of patients in elderly group
      (68.1%) showed worsening change of modified Rankin Scale than young adults
      (65.2%). Young adults ischemic stroke showed favorable hospital outcomes than the
      elderly in Korean population. 

PMID- 25045233
TI  - Incidence and risk factors of subsequent hip fractures in Korea: multicenter
      study.
AB  - This study analyzes the incidence of subsequent hip fractures and its risk
      factors in the northwestern region of Korea. We analyzed hip fracture patients
      who visited any of the 5 teaching hospitals in the Bucheon and Incheon area from
      January 2000 to December 2010. Medical records were reviewed and presence of
      subsequent hip fractures, alcohol history, marital status, live in solitude,
      dementia, dizziness, American society of anesthesiologists score, osteoporosis
      treatment after fracture, body mass index (BMI) and initial bone mineral density
      were analyzed. The average follow-up period was 12 months (range 1-130 months). A
      total of 2,546 patients (women 1,770, men 776) who had experienced hip fractures
      were included. Of these, subsequent hip fractures were found in 233 patients
      (9.2%) (women 187, men 46). Mean age at the time of the first fracture was 79.2
      yr old (range 50-100 yr). The average interval between the first fracture and the
      subsequent hip fractures was 30.2 months (range 4 days-154 months). In this large
      scale, retrospective, multicenter study, overall incidence of subsequent hip
      fractures is 9.2%. Independent risk factors of subsequent fracture are women,
      BMI<22 kg/m(2), and being unmarried. 

PMID- 25045234
TI  - The association between the low muscle mass and osteoporosis in elderly Korean
      people.
AB  - The purpose of this study was to predict osteoporosis risk as decreasing muscle
      mass and to declare the cut-off value of low muscle mass in an elderly Korean
      population. This study was based on data from the 2008-2010 Korea National Health
      and Nutritional Examination Surveys (KNHANES). The subjects included 1,308 men
      and 1,171 women over 65 yr. Bone mineral density (BMD) and appendicular skeletal
      muscle (ASM) were measured by dual energy X-ray absorptiometry (DXA), and
      appendicular skeletal muscle was adjusted by height as a marker of sarcopenia.
      After confirming the correlation between low muscle mass and BMD, the best cut
      off value of muscle mass to estimate osteoporosis was suggested through the
      receiver operating characteristic (ROC) curve. For both men and women, BMD
      correlated positively with low muscle mass when ASM/Ht(2) was used as a marker
      for sarcopenia. The ROC curve showed that ASM/Ht(2) was the best marker for
      osteoporosis at a cut-off value of 6.85 kg/m(2) for men and 5.96 kg/m(2) for
      women. When these cut-off values were used to determine sarcopenia, the risk of
      osteoporosis increased 4.14 times in men and 1.88 times in women. In particular,
      men (OR 2.12) with sarcopenia were more greatly affected than women (OR 1.15),
      even after adjusting for osteoporosis risk factors. In elderly Korean people,
      sarcopenia is positively correlated with BMD and there is a strong correlation
      between sarcopenia and osteoporosis with risk of bone fracture. 

PMID- 25045235
TI  - Does intravenous ketamine enhance analgesia after arthroscopic shoulder surgery
      with ultrasound guided single-injection interscalene block?: a randomized,
      prospective, double-blind trial.
AB  - Ketamine has anti-inflammatory, analgesic and antihyperalgesic effect and
      prevents pain associated with wind-up. We investigated whether low doses of
      ketamine infusion during general anesthesia combined with single-shot
      interscalene nerve block (SSISB) would potentiate analgesic effect of SSISB.
      Forty adult patients scheduled for elective arthroscopic shoulder surgery were
      enrolled and randomized to either the control group or the ketamine group. All
      patients underwent SSISB and followed by general anesthesia. During an operation,
      intravenous ketamine was infused to the patients of ketamine group continuously.
      In control group, patients received normal saline in volumes equivalent to
      ketamine infusions. Pain score by numeric rating scale was similar between groups
      at 1, 6, 12, 24, 36, and 48 hr following surgery, which was maintained lower than
      3 in both groups. The time to first analgesic request after admission on post
      anesthesia care unit was also not significantly different between groups.
      Intraoperative low dose ketamine did not decrease acute postoperative pain after
      arthroscopic shoulder surgery with a preincisional ultrasound guided SSISB. The
      preventive analgesic effect of ketamine could be mitigated by SSISB, which
      remains one of the most effective methods of pain relief after arthroscopic
      shoulder surgery. 

PMID- 25045236
TI  - Application of damage control resuscitation strategies to patients with severe
      traumatic hemorrhage: review of plasma to packed red blood cell ratios at a
      single institution.
AB  - When treating trauma patients with severe hemorrhage, massive transfusions are
      often needed. Damage control resuscitation strategies can be used for such
      patients, but an adequate fresh frozen plasma: packed red blood cell (FFP:PRBC)
      administration ratio must be established. We retrospectively reviewed the medical
      records of 100 trauma patients treated with massive transfusions from March 2010
      to October 2012. We divided the patients into 2 groups according to the FFP:PRBC
      ratio: a high-ratio (>=0.5) and a low-ratio group (<0.5). The patient
      demographics, fluid and transfusion quantities, laboratory values, complications,
      and outcomes were analyzed and compared. There were 68 patients in the high-ratio
      and 32 in the low-ratio group. There were statistically significant differences
      between groups in the quantities of FFP, FFP:PRBC, platelets, and crystalloids
      administered, as well as the initial diastolic blood pressure. Bloodstream
      infections were noted only in the high-ratio group, and the difference was
      statistically significant (P=0.028). Kaplan-Meier plots revealed that the 24-hr
      survival rate was significantly higher in the high-ratio group (71.9% vs. 97.1%,
      P<0.001). In severe hemorrhagic trauma, raising the FFP:PRBC ratio to 0.5 or
      higher may increase the chances of survival. Efforts to minimize bloodstream
      infections during the resuscitation must be increased. 

PMID- 25045237
TI  - A case report of preoperative and postoperative 7.0T brain MRI in a patient with
      a small cell glioblastoma.
AB  - A 45-yr-old female patient was admitted with one-month history of headache and
      progressive left hemiparesis. Brain magnetic resonance imaging (MRI) demonstrated
      a mass lesion in her right frontal lobe. Her brain tumor was confirmed as a small
      cell glioblastoma. Her follow-up brain MRI, taken at 8 months after her initial
      surgery demonstrated tumor recurrence in the right frontal lobe. Contrast
      enhanced 7.0T brain magnetic resonance imaging (MRI) was safely performed before
      surgery and at the time of recurrence. Compared with 1.5T and 3.0T brain MRI,
      7.0T MRI showed sharpened images of the brain tumor contexture with detailed
      anatomical information. The fused images of 7.0T and 1.5T brain MRI taken at the
      time of recurrence demonstrated no significant discrepancy in the positions of
      the anterior and the posterior commissures. It is suggested that 7.0T MRI can be
      safely utilized for better images of the maligant gliomas before and after
      surgery. 

PMID- 25045238
TI  - A case report of testicular sparganosis misdiagnosed as testicular tumor.
AB  - Sparganosis is a parasitic infestation of human by plerocercoid larvae. Sparganum
      is usually reported to be found in the subcutaneous tissues as well as other
      organs, including scrotum. However, testicular sparganosis is extremely rare,
      because of strong capsule of tunica albuginea. An urban-living 54-yr-old Korean
      man presented with left scrotal pain for 6 yr. Both testes look normal
      physically. Ultrasonography revealed poorly defined, heterogeneous mass with
      increased echogenicity in the left testis. This case was misdiagnosed as
      testicular tumor and underwent orchiectomy, but was diagnosed as testicular
      sparganosis by histopathology. Sparganosis should be included for differential
      diagnosis of testis tumor in countries where sparganosis is prevalent. 

PMID- 25045239
TI  - The significance of clinical and laboratory features in the diagnosis of glycogen
      storage disease type v: a case report.
AB  - Glycogen storage disease type V (GSD-V) is the most common disorder of muscle
      glycogenosis with characteristic clinical and laboratory findings. A 32-yr-old
      woman complained of exercise intolerance and myoglobulinuria since early
      adolescence. She reported several episodes of second-wind phenomenon. Physical
      examination did not show any neurological abnormality, including fixed muscle
      weakness or atrophy. Serum creatine kinase level was 1,161 IU/L at rest. The
      result of the non-ischemic forearm exercise test was compatible with GSD-V.
      Mutation analysis identified the compound heterozygous mutations of the PYGM,
      p.D510fs and p.F710del, which has not yet been reported in Korea. The present
      case recognizes that detail clinical and laboratory analysis is the first step in
      the diagnosis of GSD-V. 

PMID- 25045240
TI  - Paradoxical increase of IgE binding components during allergen-specific
      immunotherapy in pollinosis patients.
AB  - Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels
      and achieves clinical and immunological tolerance by modulating innate and
      adaptive immunological responses. Increased temperature and CO2 concentrations
      caused by climate changes contribute to an increase of pollen count and
      allergenicity that influences clinical SIT outcomes. In this study, we
      investigated the changes of IgE binding components to tree and weed pollens in
      pollinosis patients who showed a paradoxical increase of serum sIgE level during
      pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum
      sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked
      immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new
      generation of major IgE binding components that could be induced by climate
      change. The findings suggest that the regular monitoring of sIgE levels and
      symptom changes is required to improve the clinical outcomes of SIT in patients
      undergoing SIT for tree and weed pollens. 

PMID- 25045241
TI  - Patient preference and satisfaction in decision-making process.

PMID- 25045242
TI  - Bad Romance: Sex Differences in the Longitudinal Association Between Romantic
      Relationships and Deviant Behavior.
AB  - The current study investigates how romantic relationships are related to
      antisocial behavior longitudinally among delinquent males and females (n=354;
      ages 14-25). While being in a relationship or not is unrelated to antisocial
      behavior, romantic partner characteristics (antisocial behavior and antisocial
      influence) are associated with greater antisocial behavior. As males age, they
      become increasingly resistant to romantic partner characteristics. In contrast,
      females become increasingly vulnerable to the effects of romantic partner
      characteristics on antisocial behavior as they age, particularly when these
      relationships are relatively shorter. Females in shorter romantic relationships
      with partners who are antisocial or exert antisocial influence are at risk of
      persisting in antisocial behavior.

PMID- 25045243
TI  - Conducting Health Disparities Research with Criminal Justice Populations:
      Examining Research, Ethics, and Participation.
AB  - This study explored the challenges of informed consent and understanding of the
      research process among Black and Latino men under community supervision (e.g.,
      parole and/or probation). Between February and October 2012, we conducted
      cognitive face-to-face interviews using open-ended questions on the significant
      areas of research participation (i.e., the informed consent process,
      confidentiality, compensation, what is meant by human subject and clinical
      trials) among 259 men aged 35 to 67 under community supervision in Bronx, New
      York. Content analysis of the open-ended questions revealed limited knowledge
      concerning the understanding of research participation. The study participants
      appeared to generally understand concepts such as compensation after research
      participation and confidentiality. Participants demonstrated a lack of
      understanding of certain aspects of the research process-informed consent, human
      subject, Institutional Review Board, and clinical trials. These findings are
      informative to researchers conducting studies with criminal justice populations
      and Institutional Review Boards reviewing research studies.

PMID- 25045244
TI  - Understanding the Link between Poverty and Food Insecurity among Children: Does
      the Definition of Poverty Matter?
AB  - This paper examines the association between poverty and food insecurity among
      children, using two different definitions of poverty-the official poverty measure
      (OPM) and the new supplemental poverty measure (SPM) of the Census Bureau, which
      is based on a more inclusive definition of family resources and needs. Our
      analysis is based on data from the 2001-11 Current Population Survey and shows
      that food insecurity and very low food security among children decline as income
      to-needs ratio increases. The point estimates show that the associations are
      stronger as measured by the new supplemental measure of income-to-needs ratio
      than when estimated through the official measure. Statistical tests reject the
      hypothesis that poor households' odds of experiencing low food security are the
      same whether the SPM or OPM measure is used; but the tests do not reject the
      hypothesis when very low food security is the outcome.

PMID- 25045246
TI  - Treatment of dystrophic calcification on a silicone intraocular lens with pars
      plana vitrectomy.
AB  - PURPOSE: Dense, vision-obscuring calcification on the posterior aspect of
      silicone intraocular lenses (IOLs) is often not amenable to neodymium:yttrium
      aluminum-garnet capsulotomy, and, in prior reports, has required IOL exchange. We
      report the successful removal of dense calcium deposition on the posterior
      surface of a three-piece silicone lens using pars plana vitrectomy (PPV).
      MATERIALS AND METHODS: A 23-gauge PPV was performed using the Stellaris((r))
      vitrectomy system. A light pipe was used to retroilluminate the IOL, and a dense
      fibrous tissue setting with a low cut-rate and high aspiration rate was able to
      clear the visual axis of the dystrophic calcification without damaging the IOL
      optic. RESULTS: Visual acuity improved from 20/100 to 20/25. CONCLUSION: Small
      gauge PPV may be utilized to remove dense dystrophic calcium deposits on the lens
      surface in lieu of IOL exchange.

PMID- 25045245
TI  - Perceived Neighborhood Safety and Adolescent School Functioning.
AB  - This study examined the association between adolescents' perceptions of their
      neighborhoods' safety and multiple elements of their functioning in school with
      data on 15 year olds from the NICHD Study of Early Child Care and Youth
      Development (n = 924). In general, perceived neighborhood safety was more
      strongly associated with aspects of schooling that were more psychosocial in
      nature (e.g., school attachment) than those that were more cognitive (e.g., test
      scores). Examination of neighborhood and family moderators of these associations
      revealed that perceived neighborhood safety was negatively associated with grades
      for youth from low-income families but was positively associated with school
      attachment for youth from such families when they lived in neighborhoods rated by
      observers as high in physical disorder.

PMID- 25045247
TI  - Review of nemonoxacin with special focus on clinical development.
AB  - Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone with remarkably
      enhanced in vitro activity against a wide variety of clinically relevant
      pathogens, especially gram-positive bacteria, including multidrug-resistant
      Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. It has
      a low propensity for selecting resistant pathogens than fluoroquinolones, since
      bacteria become resistant to nemonoxacin only when three different mutations
      occur in their quinolone resistance-determining regions. Nemonoxacin shows
      greater efficacy than most of the widely used fluoroquinolones in the murine
      model of systemic, pulmonary, or ascending urinary tract infection. Nemonoxacin
      has a sound PK profile in healthy volunteers. It rapidly reaches maximum
      concentration Cmax 1-2 hours after oral administration in the fasting state and
      has a relatively long elimination half-life of more than 10 hours, which is
      similar to fluoroquinolones. Approximately 60%-75% of the administered dose is
      excreted in unchanged form via kidneys over 24-72 hours. Phase II and III studies
      of oral nemonoxacin and Phase II studies of intravenous nemonoxacin have been
      completed in patients with community-acquired pneumonia (CAP), before which the
      Phase I studies of oral and intravenous nemonoxacin indicated sound tolerance and
      safety with healthy volunteers. The published results demonstrate that an oral
      dose of either 500 mg or 750 mg nemonoxacin once daily for 7 days is as effective
      and safe as levofloxacin 500 mg once daily for 7 days. Nemonoxacin is well
      tolerated in patients with CAP. The most common adverse events of oral
      administration are observed in the gastrointestinal and nervous system, the
      incidence of which is similar to levofloxacin treatment. The Phase III studies of
      intravenous nemonoxacin for treating CAP and oral nemonoxacin for diabetic foot
      infection has been registered with promising outcomes to be expected. 

PMID- 25045249
TI  - Dexmedetomidine for awake intubation and an opioid-free general anesthesia in a
      superobese patient with suspected difficult intubation.
AB  - Super-obese patients (body mass index [BMI] >50 kg/m(2)) are at a particularly
      high risk of anesthesia-related complications during postoperative period, eg,
      critical respiratory events including respiratory arrest, and over-sedation
      leading to problems with maintaining airway open, hypoxia and hypercapnia. In
      this paper authors present a case of a 39-year-old super-obese (BMI 62.3 kg/m(2))
      female patient who was admitted for surgical treatment of obesity. Preanesthesia
      evaluation revealed hypertension and type 2 diabetes mellitus (DM) as
      comorbidities as well as potential for a difficult intubation- neck circumference
      of 46 cm, reduced neck mobility and DM type 2. Patient was intubated using "awake
      intubation" method using topical anesthesia and dexmedetomidine infusion. General
      anesthesia was maintained with sevoflurane and dexmedetomidine infusion instead
      of opioid administration in "opioid-free anesthesia method". 

PMID- 25045248
TI  - Design of oral agents for the management of multiple sclerosis: benefit and risk
      assessment for dimethyl fumarate.
AB  - Dimethyl fumarate (DMF) is the most recent oral disease-modifying therapy
      approved by the US Food and Drug Administration and is indicated for the
      treatment of relapsing forms of multiple sclerosis (MS). Prior to approval for
      use in MS, DMF and its active metabolite, monomethyl fumarate, had been used for
      decades as two of the fumaric acid esters in Fumaderm, a medication used in
      Europe for the treatment of psoriasis. The unique mechanism of action of DMF
      remains under evaluation; however, it has been shown to act through multiple
      pathways leading to shifts away from the Th1 proinflammatory response to the less
      inflammatory Th2 response. Preliminary data suggest that DMF may induce
      neuroprotective effects in central nervous system white matter, although further
      studies are needed to demonstrate these effects on inflammatory demyelination.
      The DMF Phase III clinical trials demonstrated its efficacy with regard to a
      reduction in the annualized relapse rate and reductions in new or enlarging T2
      lesions and numbers of gadolinium-enhancing lesions on magnetic resonance
      imaging. DMF has a well-defined safety profile, given the experience with its use
      in the treatment of psoriasis, and more recently from the DMF clinical trials
      program and post-marketing era for treatment of MS. The safety profile and oral
      mode of administration of DMF place it as an attractive first-line therapy option
      for the treatment of relapsing forms of MS. Long-term observational studies will
      be needed to determine the effects of DMF on progression of disability in MS.

PMID- 25045251
TI  - Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5
      fluorouracil in murine liver cancer model via regulatory T-cells [Retraction].

PMID- 25045250
TI  - Drug delivery options to increase patient adherence and satisfaction in the
      management of rheumatoid arthritis -- focus on subcutaneous tocilizumab.
AB  - Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease
      associated with joint destruction. Tocilizumab (TCZ) is a humanized monoclonal
      anti-interleukin-6 receptor antibody that was initially developed for use as an
      intravenous (IV) infusion. Previous studies have shown that TCZ-IV is an
      important treatment option in patients with moderate-to-severe RA. A subcutaneous
      (SC) formulation of 162 mg TCZ that was recently developed and approved provides
      an additional treatment option for RA patients. In the present review, we provide
      an update on the efficacy and safety of TCZ-SC, compared with TCZ-IV. The TCZ-SC
      doses of 162 mg every 2 weeks (q2w) or weekly (qw) were selected based on
      pharmacokinetic and pharmacodynamic studies. Both TCZ-SC q2w and qw regimens
      showed equivalent effects to TCZ-IV in most patients; however, the TCZ-SC qw
      regimen consistently showed a more rapid effect in terms of C-reactive protein
      normalization. Randomized controlled studies showed that TCZ-SC monotherapy or
      combined with disease-modifying antirheumatic drugs demonstrated comparable
      efficacy to TCZ-IV in patients who were both biologic-naive and refractory to
      tumor necrosis factor inhibitors. TCZ-SC at both qw and q2w were generally well
      tolerated for up to 24 weeks. There was a low rate of withdrawal due to adverse
      events, and their incidence was comparable with that seen with TCZ-IV. An
      injection site reaction was seen in approximately 10% of patients who received
      the subcutaneous formulation. In conclusion, although clinical results are still
      limited, the currently available evidence suggests that TCZ-SC is a promising
      treatment for moderate-to-severe RA, both as monotherapy and combination therapy.
      More data is needed to determine the optimal dosing schedule. 

PMID- 25045252
TI  - Subcutaneous bortezomib for multiple myeloma treatment: patients' benefits.
AB  - The use of novel agents such as thalidomide, lenalidomide, and bortezomib has
      considerably improved the outcome of multiple myeloma patients. Besides greater
      biological activity, these drugs unfortunately have also been associated with
      greater toxicity. To evaluate the positive effect on the quality of life of
      patients, driven by both the tolerability and antimyeloma activity of bortezomib,
      we analyzed data that have been published concerning different strategies used to
      improve its tolerability as once weekly and/or subcutaneous administration. 

PMID- 25045253
TI  - Effect of a health coaching self-management program for older adults with
      multimorbidity in nursing homes.
AB  - BACKGROUND AND AIMS: Although a growing number of older people are suffering from
      multimorbidity, most of the health problems related to multimorbidity can be
      improved by self-management. The aim of this study was to examine the
      effectiveness of a health coaching self-management program for older adults with
      multimorbidity in nursing homes. METHODS: Older adults with multimorbidity from
      one nursing home in Korea were randomly allocated to either an intervention group
      (n=22) or conventional group (n=21). Participants in the intervention group met
      face to face with the researchers twice a week for 8 weeks, during which time the
      researchers engaged them in goal setting and goal performance using the
      strategies in the health coaching self-management program. Regular care was
      provided to the other participants in the conventional group. RESULTS:
      Participants in the intervention group had significantly better outcomes in
      exercise behaviors (P=0.015), cognitive symptom management (P=0.004), mental
      stress management/relaxation (P=0.023), self-rated health (P=0.002), reduced
      illness intrusiveness (P<0.001), depression (P<0.001), and social/role activities
      limitations (P<0.001). In addition, there was a significant time-by-group
      interaction in self-efficacy (P=0.036). According to the goal attainment scales,
      their individual goals of oral health and stress reduction were achieved.
      CONCLUSION: The health coaching self-management program was successfully
      implemented in older adults with multimorbidity in a nursing home. Further
      research is needed to develop and evaluate the long-term effects of an
      intervention to enhance adherence to self-management and quality of life for
      older adults with multimorbidity.

PMID- 25045254
TI  - Patient perspectives on switching disease-modifying therapies in the NARCOMS
      registry.
AB  - INTRODUCTION: The evolving landscape of disease-modifying therapies (DMTs) for
      multiple sclerosis raises important questions about why patients change DMTs.
      Physicians and patients could benefit from a better understanding of the reasons
      for switching therapy. PURPOSE: To investigate the reasons patients switch DMTs
      and identify characteristics associated with the decision to switch. METHOD: The
      North American Research Committee on Multiple Sclerosis (NARCOMS) Registry
      conducted a supplemental survey among registry participants responding to the
      2011 update survey. The supplemental survey investigated reasons for switching
      DMT, origin of the discussion of DMT change, and which factors influenced the
      decision. Chi-square tests, Fisher's exact tests, and logistic regression were
      used for the analyses. RESULTS: Of the 691 eligible candidates, 308 responded and
      met the inclusion criteria (relapsing disease course, switched DMT after
      September 2010). The responders were 83.4% female, on average 52 years old, with
      a median (interquartile range) Patient-Determined Disease Steps score of 4 (2-5).
      The most recent prior therapy included first-line injectables (74.5%), infusions
      (18.1%), an oral DMT (3.4%), and other DMTs (4.0%). The discussion to switch DMT
      was initiated almost equally by physicians and participants. The primary reason
      for choosing the new DMT was based most frequently on physician's recommendation
      (24.5%) and patient perception of efficacy (13.7%). CONCLUSION: Participants
      frequently initiated the discussion regarding changing DMT, although physician
      recommendations regarding the specific therapy were still weighed highly. Long
      term follow-up of these participants will provide valuable information on their
      disease trajectory, satisfaction with, and effectiveness of their new medication.

PMID- 25045255
TI  - Clinical advances in the management of chronic myelogenous leukemia: focus on
      bosutinib and patient considerations.
AB  - The treatment for chronic myeloid leukemia has changed significantly over the
      past 15 years, and as of now, there are five BCR-ABL1 (breakpoint cluster region
      Abelson murine leukemia viral oncogene homolog 1) tyrosine kinase inhibitors that
      have gained approval for treatment of this disease. All five are very effective
      drugs, and the decision surrounding which to use in specific patients is based on
      numerous factors. Bosutinib is one of the newer tyrosine kinase inhibitors to
      gain approval, and has been studied in the first-line setting as well as after
      failure of other tyrosine kinase inhibitors. It is an SRC-ABL1 (steroid receptor
      co-activator-ABL1) inhibitor that works in the presence of most kinase domain
      mutations. The primary side effects of bosutinib are gastrointestinal upsets. In
      the appropriate clinical setting, bosutinib can be considered a valuable addition
      to the armamentarium of treatments available for chronic myeloid leukemia. 

PMID- 25045256
TI  - Effect of Feldenkrais exercises on dual task postural control in older adults.

PMID- 25045257
TI  - Additive effects of nutritional supplementation, together with bisphosphonates,
      on bone mineral density after hip fracture: a 12-month randomized controlled
      study.
AB  - BACKGROUND: After a hip fracture, a catabolic state develops, with increased bone
      loss during the first year. The aim of this study was to evaluate the effects of
      postoperative treatment with calcium, vitamin D, and bisphosphonates (alone or
      together) with nutritional supplementation on total hip and total body bone
      mineral density (BMD). METHODS: Seventy-nine patients (56 women), with a mean age
      of 79 years (range, 61-96 years) and with a recent hip fracture, who were
      ambulatory before fracture and without severe cognitive impairment, were
      included. Patients were randomized to treatment with bisphosphonates (risedronate
      35 mg weekly) for 12 months (B; n=28), treatment with bisphosphonates along with
      nutritional supplementation (40 g protein, 600 kcal daily) for the first 6 months
      (BN; n=26), or to controls (C; n=25). All participants received calcium (1,000
      mg) and vitamin D3 (800 IU) daily. Total hip and total body BMD were assessed
      with dual-energy X-ray absorptiometry at baseline, 6, and 12 months. Marker of
      bone resorption C-terminal telopeptide of collagen I and 25-hydroxy vitamin D
      were analyzed in serum. RESULTS: Analysis of complete cases (70/79 at 6 months
      and 67/79 at 12 months) showed an increase in total hip BMD of 0.7% in the BN
      group, whereas the B and C groups lost 1.1% and 2.4% of BMD, respectively,
      between baseline and 6 months (P=0.071, between groups). There was no change in
      total body BMD between baseline and 12 months in the BN group, whereas the B
      group and C group both lost BMD, with C losing more than B (P=0.009). Intention
      to-treat analysis was in concordance with the complete cases analyses.
      CONCLUSION: Protein-and energy-rich supplementation in addition to calcium,
      vitamin D, and bisphosphonate therapy had additive effects on total body BMD and
      total hip BMD among elderly hip fracture patients.

PMID- 25045258
TI  - Lung function efficacy and symptomatic benefit of olodaterol once daily delivered
      via Respimat(r) versus placebo and formoterol twice daily in patients with GOLD 2
      4 COPD: results from two replicate 48-week studies.
AB  - Two replicate, multicenter, randomized, double-blind, placebo-controlled,
      parallel-group, Phase III studies investigated the long-term efficacy and safety
      of once-daily olodaterol via Respimat(r) versus placebo and formoterol over 48
      weeks in patients with moderate to very severe chronic obstructive pulmonary
      disease receiving usual-care background therapy. Patients received once-daily
      olodaterol 5 or 10 MUg, twice-daily formoterol 12 MUg, or placebo. Co-primary end
      points were forced expiratory volume in 1 second (FEV1) area under the curve from
      0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index
      total score after 24 weeks; secondary end points included St George's Respiratory
      Questionnaire. Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients
      received treatment. Olodaterol significantly improved FEV1 area under the curve
      from 0-3 hours versus placebo in both studies (with olodaterol 5 MUg, 0.151 L and
      0.129 L; with olodaterol 10 MUg, 0.165 L and 0.154 L; for all comparisons
      P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as
      did formoterol. Primary analysis revealed no significant difference in transition
      dyspnea index focal score for any active treatment versus placebo. Post hoc
      analysis using pattern mixture modeling (accounting for discontinuations)
      demonstrated statistical significance for olodaterol versus placebo. St George's
      Respiratory Questionnaire total score was significantly improved with olodaterol,
      but not formoterol, versus placebo. No safety signals were identified from
      adverse-event or other safety data. Once-daily olodaterol 5 MUg and 10 MUg is
      efficacious in patients with moderate to very severe chronic obstructive
      pulmonary disease on usual-care maintenance therapy, with a satisfactory safety
      profile.

PMID- 25045259
TI  - Dose intensity and autologous stem cell transplantation as salvage therapy for
      pediatric primary CNS malignancies.

PMID- 25045260
TI  - Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in
      pulmonary arteries.
AB  - Prostacyclin analogues are standard therapeutic options for vasoconstrictive
      diseases, including pulmonary hypertension and Raynaud's phenomenon. Although
      effective, these treatment strategies are expensive and have several side
      effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier
      systems. In this study, we synthesized liposomal nanoparticles tailored for the
      prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on
      mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids,
      stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in
      liposomes promoted iloprost encapsulation to at least 50%. The addition of
      cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle
      formulations were tested for toxicity and pharmacologic efficacy in vivo and ex
      vivo, respectively. The liposomes did not affect the viability of human pulmonary
      artery smooth muscle cells. Compared with an equivalent concentration of free
      iloprost, four out of the six polymer-coated liposomal formulations exhibited
      significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that
      was encapsulated in liposomes containing the polymer polyethylene glycol
      exhibited concentration-dependent relaxation of arteries. Strikingly, half the
      concentration of iloprost in liposomes elicited similar pharmacologic efficacy as
      nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high
      efficacy and can serve as potential iloprost carriers to improve its therapeutic
      efficacy. 

PMID- 25045261
TI  - Nanoformulated cell-penetrating survivin mutant and its dual actions.
AB  - In this study, we investigated the differential actions of a dominant-negative
      survivin mutant (SurR9-C84A) against cancerous SK-N-SH neuroblastoma cell lines
      and differentiated SK-N-SH neurons. In both the cases, the mutant protein
      displayed dual actions, where its effects were cytotoxic toward cancerous cells
      and proliferative toward the differentiated neurons. This can be explained by the
      fact that tumorous (undifferentiated SK-N-SH) cells have a high endogenous
      survivin pool and upon treatment with mutant SuR9-C84A causes forceful survivin
      expression. These events significantly lowered the microtubule dynamics and
      stability, eventually leading to apoptosis. In the case of differentiated SK-N-SH
      neurons that express negligible levels of wild-type survivin, the mutant
      indistinguishably behaved in a wild-type fashion. It also favored cell-cycle
      progression, forming the chromosome-passenger complex, and stabilized the
      microtubule-organizing center. Therefore, mutant SurR9-C84A represents a novel
      therapeutic with its dual actions (cytotoxic toward tumor cells and protective
      and proliferative toward neuronal cells), and hence finds potential applications
      against a variety of neurological disorders. In this study, we also developed a
      novel poly(lactic-co-glycolic acid) nanoparticulate formulation to surmount the
      hurdles associated with the delivery of SurR9-C84A, thus enhancing its effective
      therapeutic outcome. 

PMID- 25045263
TI  - Understanding improved osteoblast behavior on select nanoporous anodic alumina.
AB  - The aim of this study was to prepare different sized porous anodic alumina (PAA)
      and examine preosteoblast (MC3T3-E1) attachment and proliferation on such
      nanoporous surfaces. In this study, PAA with tunable pore sizes (25 nm, 50 nm,
      and 75 nm) were fabricated by a two-step anodizing procedure in oxalic acid. The
      surface morphology and elemental composition of PAA were characterized by field
      emission scanning electron microscopy and X-ray photoelectron spectroscopy
      analysis. The nanopore arrays on all of the PAA samples were highly regular. X
      ray photoelectron spectroscopy analysis suggested that the chemistry of PAA and
      flat aluminum surfaces were similar. However, contact angles were significantly
      greater on all of the PAA compared to flat aluminum substrates, which
      consequently altered protein adsorption profiles. The attachment and
      proliferation of preosteoblasts were determined for up to 7 days in culture using
      field emission scanning electron microscopy and a Cell Counting Kit-8. Results
      showed that nanoporous surfaces did not enhance initial preosteoblast attachment,
      whereas preosteoblast proliferation dramatically increased when the PAA pore size
      was either 50 nm or 75 nm compared to all other samples (P<0.05). Thus, this
      study showed that one can alter surface energy of aluminum by modifying surface
      nano-roughness alone (and not changing chemistry) through an anodization process
      to improve osteoblast density, and, thus, should be further studied as a
      bioactive interface for orthopedic applications. 

PMID- 25045262
TI  - Nanoparticle delivery and combination therapy of gambogic acid and all-trans
      retinoic acid.
AB  - In order to enhance the in vivo codelivery efficiency of gambogic acid (GA) and
      all-trans retinoic acid (ATRA), our strategy was to entrap GA in the self
      assembled nanoparticles based on amphiphilic hyaluronic acid (HA)-ATRA (HRA)
      conjugate. In this way, GA and ATRA were loaded simultaneously in a nanocarrier
      and codelivered into the tumor cell through HA receptor-mediated endocytosis. GA
      loaded HRA nanoparticles (GA-HRA) were prepared by a dialysis method, and their
      physicochemical characteristics were investigated as well. GA-HRA exhibited a
      high drug loading capacity (31.1%), had a particle size in the range of 100-150
      nm, and good biocompatibility. HRA nanoparticles were effectively internalized by
      MCF-7 cells and translocated into the nucleus in a time-dependent manner. The in
      vivo imaging analysis demonstrated that the fluorescent signals in the tumor were
      markedly increased with DiR-loaded nanoparticles after intravenous administration
      compared to free DiR solution, suggesting it has excellent tumor targeting
      properties. More importantly, GA-HRA exhibited excellent in vivo efficacy with
      dramatically reduced toxicity. In conclusion, with the assistance of HRA
      nanoparticles, GA and ATRA can successfully realize an effective combination
      chemotherapy as well as tumor-targeted delivery. 

PMID- 25045264
TI  - Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine
      within archaeolipids containing liposomes.
AB  - In this work, the in vitro anti-Leishmania activity of photodynamic liposomes
      made of soybean phosphatidylcholine, sodium cholate, total polar archaeolipids
      (TPAs) extracted from the hyperhalophile archaea Halorubrum tebenquichense and
      the photosensitizer zinc phthalocyanine (ZnPcAL) was compared to that of
      ultradeformable photodynamic liposomes lacking TPAs (ZnPcUDLs). We found that
      while ZnPcUDLs and ZnPcALs (130 nm mean diameter and -35 mV zeta potential) were
      innocuous against promastigotes, a low concentration (0.01 MUM ZnPc and 7.6 MUM
      phospholipids) of ZnPcALs irradiated at a very low-energy density (0.2 J/cm(2))
      eliminated L. braziliensis amastigotes from J774 macrophages, without reducing
      the viability of the host cells. In such conditions, ZnPcALs were harmless for
      J774 macrophages, HaCaT keratinocytes, and bone marrow-derived dendritic cells.
      Therefore, topical photodynamic treatment would not likely affect skin-associated
      lymphoid tissue. ZnPcALs were extensively captured by macrophages, but ZnPcUDLs
      were not, leading to 2.5-fold increased intracellular delivery of ZnPc than with
      ZnPcUDLs. Despite mediating low levels of reactive oxygen species, the higher
      delivery of ZnPc and the multiple (caveolin- and clathrin-dependent plus
      phagocytic) intracellular pathway followed by ZnPc would have been the reason for
      the higher antiamastigote activity of ZnPcALs. The leishmanicidal activity of
      photodynamic liposomal ZnPc was improved by TPA-containing liposomes. 

PMID- 25045265
TI  - Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron
      oxide for reduction-responsive gene delivery and magnetic resonance imaging.
AB  - Theranostic nanoparticles based on superparamagnetic iron oxide (SPIO) have a
      great promise for tumor diagnosis and gene therapy. However, the availability of
      theranostic nanoparticles with efficient gene transfection and minimal toxicity
      remains a big challenge. In this study, we construct an intelligent SPIO-based
      nanoparticle comprising a SPIO inner core and a disulfide-containing
      polyethylenimine (SSPEI) outer layer, which is referred to as a SSPEI-SPIO
      nanoparticle, for redox-triggered gene release in response to an intracellular
      reducing environment. We reveal that SSPEI-SPIO nanoparticles are capable of
      binding genes to form nano-complexes and mediating a facilitated gene release in
      the presence of dithiothreitol (5-20 mM), thereby leading to high transfection
      efficiency against different cancer cells. The SSPEI-SPIO nanoparticles are also
      able to deliver small interfering RNA (siRNA) for the silencing of human
      telomerase reverse transcriptase genes in HepG2 cells, causing their apoptosis
      and growth inhibition. Further, the nanoparticles are applicable as T2-negative
      contrast agents for magnetic resonance (MR) imaging of a tumor xenografted in a
      nude mouse. Importantly, SSPEI-SPIO nanoparticles have relatively low
      cytotoxicity in vitro at a high concentration of 100 MUg/mL. The results of this
      study demonstrate the utility of a disulfide-containing cationic polymer
      decorated SPIO nanoparticle as highly potent and low-toxic theranostic nano
      system for specific nucleic acid delivery inside cancer cells. 

PMID- 25045266
TI  - Investigation of health anxiety and its related factors in nursing students.
AB  - OBJECTIVE: To explore health anxiety in a sample of nursing students to determine
      the relationships between health anxiety and life satisfaction, personality, and
      alexithymia. METHODS: Two thousand and eighty-six nursing students in junior
      college, which were divided into five groups, were evaluated by questionnaires,
      including the Life Satisfaction Scales Applicable to College Students, the
      Chinese version of the Short Health Anxiety Inventory, the Toronto Alexithymia
      Scale (TAS-20), and the Eysenck Personality Questionnaire. RESULTS: The mean age,
      whether the individual was an only child, residence (urban or rural), and were
      significantly different between the groups. The self-assessment scores were also
      significantly different between the groups. The Short Health Anxiety Inventory
      total score and the factor of fearing the likelihood of becoming ill were
      significantly negatively correlated with the Life Satisfaction Scales Applicable
      to College Students total score and its two factors, but were significantly
      positively correlated with psychoticism, neuroticism, and TAS-20 total scores and
      its scores of the three TAS-20 factors. The negative consequence scale of Short
      Health Anxiety Inventory was not significantly correlated with externally
      oriented thinking, but was significantly negatively correlated with extraversion.
      A hierarchical multiple regression analysis indicted that objective satisfaction,
      subjective satisfaction, neuroticism, and the three factors of TAS-20 were
      predictors of health anxiety. CONCLUSION: Health anxiety was correlated with life
      satisfaction, personality, and alexithymia in junior college nursing students.
      Subjective and objective satisfaction, neuroticism, and the identification and
      expression of emotions may be predictors of health anxiety in nursing students.

PMID- 25045267
TI  - Depression, 5HTTLPR and BDNF Val66Met polymorphisms, and plasma BDNF levels in
      hemodialysis patients with chronic renal failure.
AB  - OBJECTIVE: Depression is the most prevalent comorbid psychiatric disease among
      hemodialysis patients with end-stage renal disease. This cross-sectional study
      investigated whether depression in hemodialysis patients is associated with the
      polymorphism of the 5' flanking transcriptional region (5-HTTLPR) of the
      serotonin transporter gene, the valine (Val)-to-methionine (Met) substitution at
      codon 66 (Val66Met) polymorphism of the brain-derived neurotrophic factor (BDNF)
      gene, or plasma BDNF levels. METHODS: A total of 188 participants (mean age:
      58.5+/-14.0 years; 89 men and 99 women) receiving hemodialysis at the Chang Gung
      Memorial Hospital were recruited. The diagnosis of major depressive disorder
      (MDD) was confirmed using the Chinese version of the Mini International
      Neuropsychiatric Interview. The genotypes of 5-HTTLPR and BDNF Val66Met were
      conducted using polymerase chain reactions plus restriction fragment length
      polymorphism analysis. The plasma BDNF levels were measured using an enzyme
      linked immunosorbent assay kit. RESULTS: Forty-five (23.9%) patients fulfilled
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV
      TR) criteria for a MDD. There were no significant effects of the 5-HTTLPR or BDNF
      Val66Met gene polymorphism on MDD among the hemodialysis patients. The plasma
      BDNF levels correlated significantly with age (P=0.003) and sex (P=0.047) but not
      with depression, the genotypes of 5-HTTLPR and BDNF Val66Met, the current
      antidepressant treatment, or the duration under hemodialysis. CONCLUSION: Our
      results did not support the hypothesis of an involvement of the 5HTTLPR and BDNF
      Val66Met genotypes, or plasma BDNF levels in the pathogenesis of depression, in
      patients receiving hemodialysis. A study with a large sample size and homogenous
      patient group is warranted to confirm these findings.

PMID- 25045268
TI  - The effect of atypical antipsychotics on brain N-acetylaspartate levels in
      antipsychotic-naive first-episode patients with schizophrenia: a preliminary
      study.
AB  - PURPOSE: To investigate the correlates of a clinical therapeutic response by
      using the parameters measured by proton magnetic resonance spectroscopy after the
      administration of atypical antipsychotics. PATIENTS AND METHODS: Twenty-five
      antipsychotic-naive first-episode patients with schizophrenia were monitored for
      12 months. The patients were evaluated using (1)H magnetic resonance spectroscopy
      in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale,
      Clinical Global Impression Scale of Severity, Tower of London - Drexel
      University, Letter-Number Span Test, Trail Making Test A, and Personal and Social
      Performance Scale. They were administered atypical antipsychotics, starting with
      quetiapine. In the absence of a therapeutic response, another antipsychotic was
      introduced. RESULTS: After 12 study months, the N-acetylaspartate/creatine
      (NAA/Cr) level did not significantly change at the whole-group level. Additional
      analysis revealed a significant rise in the NAA/Cr level in the study group that
      stayed on the same antipsychotic throughout the study course (P=0.008) and a
      significant drop in NAA/Cr in the study group that switched antipsychotics
      (P=0.005). On the whole-group level, no significant correlations between NAA/Cr
      values and other scores were found at either baseline or after 12 study months.
      CONCLUSION: One-year treatment with atypical antipsychotics administered to
      antipsychotic-naive patients didn't result in a significant rise in the NAA/Cr
      ratio. However, a significant rise was witnessed in the study group in which a
      satisfactory therapeutic response had been achieved with a single antipsychotic
      administration.

PMID- 25045269
TI  - Apotemnophilia, body integrity identity disorder or xenomelia? Psychiatric and
      neurologic etiologies face each other.
AB  - This review summarizes the available studies of a rare condition in which
      individuals seek the amputation of a healthy limb or desire to be paraplegic.
      Since 1977, case reports and group studies have been produced, trying to
      understand the cause of this unusual desire. The main etiological hypotheses are
      presented, from the psychological/psychiatric to the most recent neurologic
      explanation. The paradigms adopted and the clinical features are compared across
      studies and analyzed in detail. Finally, future directions and ethical
      implications are discussed. A proposal is made to adopt a multidisciplinary
      approach that comprises state-of-the-art technologies and a variety of
      theoretical models, including both body representation and psychological and
      sexual components. 

PMID- 25045270
TI  - Cerebral palsy in Al-Quseir City, Egypt: prevalence, subtypes, and risk factors.
AB  - Cerebral palsy (CP) is the most frequent cause of motor handicap. The present
      door-to-door survey was conducted in Al-Quseir City, Egypt, to investigate the
      epidemiology of CP. All inhabitants were screened by three neurologists. Medical
      and neurological examinations were performed for all residents and suspected
      cases of CP were confirmed by meticulous neurological assessment, brain magnetic
      resonance imaging, electroencephalography, and testing with the Stanford-Binet
      Intelligence Scale. Forty-six of 12,788 children aged <=18 years were found to
      have CP, yielding a childhood prevalence of 3.6 (95% confidence interval 1.48
      2.59) per 1,000 live births. Five adults (aged 19-40 years) among 13,056
      inhabitants had CP, giving an adult prevalence of 0.4 (95% confidence interval
      0.04-0.72) per 1,000. The risk factors for CP identified in this study were
      premature birth, low birth weight, neonatal jaundice, neonatal seizures, and
      recurrent abortion in mothers of children with CP. 

PMID- 25045272
TI  - When the struggle against dejection becomes a part of everyday life: a
      qualitative study of coping strategies in older abused people.
AB  - BACKGROUND: Abuse of older people is a serious issue and is associated with an
      increased risk of morbidity and mortality, and professionals will encounter
      elderly victims of abuse in all areas of the health care system. An important
      health determinant is behavioral factors, including coping style, which will
      impact on how older people manage stress and maintain control in their lives, and
      thereby protect themselves from abuse. The aim of this study was to explore the
      coping strategies elderly people abused by their offspring used to manage
      everyday life. METHODS: A qualitative approach was used and 14 elderly victims of
      abuse were interviewed. The interviews were recorded, transcribed, and subjected
      to qualitative content analysis. RESULTS: Five main coping strategies were
      identified. The main strategy was linked to the role of parent. Another prominent
      strategy was attitude towards being victimized. Further strategies were
      associated with hope for a better relationship with offspring in the future,
      while others felt that they had done the best they could, or that their offspring
      were no longer their responsibility. The results are discussed in light of
      theoretical perspectives related to coping and resilience. CONCLUSION: Abuse of
      older people by their offspring imposes severe stress on victims and challenges
      the values and beliefs about the caring nature of families. The findings of this
      study indicate that victims of abuse use a wide range of coping techniques to
      manage everyday life, and that some strategies help them to maintain their self
      respect in their role as parents and find some sort of resilience.

PMID- 25045271
TI  - Carotid revascularization: risks and benefits.
AB  - Despite a decline during the recent decades in stroke-related death, the
      incidence of stroke has remained unchanged or slightly increased, and
      extracranial carotid artery stenosis is implicated in 20%-30% of all strokes.
      Medical therapy and risk factor modification are first-line therapies for all
      patients with carotid occlusive disease. Evidence for the treatment of patients
      with symptomatic carotid stenosis greater than 70% with either carotid artery
      stenting (CAS) or carotid endarterectomy (CEA) is compelling, and several trials
      have demonstrated a benefit to carotid revascularization in the symptomatic
      patient population. Asymptomatic carotid stenosis is more controversial, with the
      largest trials only demonstrating a 1% per year risk stroke reduction with CEA.
      Although there are sufficient data to advocate for aggressive medical therapy as
      the primary mode of treatment for asymptomatic carotid stenosis, there are also
      data to suggest that certain patient populations will benefit from a stroke risk
      reduction with carotid revascularization. In the United States, consensus and
      practice guidelines dictate that CEA is reasonable in patients with high-grade
      asymptomatic stenosis, a reasonable life expectancy, and perioperative risk of
      less than 3%. Regarding CAS versus CEA, the best-available evidence demonstrates
      no difference between the two procedures in early perioperative stroke,
      myocardial infarction, or death, and no difference in 4-year ipsilateral stroke
      risk. However, because of the higher perioperative risks of stroke in patients
      undergoing CAS, particularly in symptomatic, female, or elderly patients, it is
      difficult to recommend CAS over CEA except in populations with prohibitive
      cardiac risk, previous carotid surgery, or prior neck radiation. Current
      treatment paradigms are based on identifying the magnitude of perioperative risk
      in patient subsets and on using predictive factors to stratify patients with high
      risk asymptomatic stenosis. 

PMID- 25045273
TI  - Role of calcium-dependent protein kinases in chronic myeloid leukemia: combined
      effects of PKC and BCR-ABL signaling on cellular alterations during leukemia
      development.
AB  - Calcium-dependent protein kinases (PKCs) function in a myriad of cellular
      processes, including cell-cycle regulation, proliferation, hematopoietic stem
      cell differentiation, apoptosis, and malignant transformation. PKC inhibitors,
      when targeted to these pathways, have demonstrated efficacy against several types
      of solid tumors as well as leukemia. Chronic myeloid leukemia (CML) represents
      20% of all adult leukemia. The aberrant Philadelphia chromosome has been reported
      as the main cause of CML development in hematopoietic stem cells, due to the
      formation of the BCR-ABL oncogene. PKCs and BCR-ABL coordinate several signaling
      pathways that are crucial to cellular malignant transformation. Experimental and
      clinical evidence suggests that pharmacological approaches using PKC inhibitors
      may be effective in the treatment of CML. This mini review summarizes articles
      from the National Center for Biotechnology Information website that have shown
      evidence of the involvement of PKC in CML. 

PMID- 25045274
TI  - Actinomycosis: etiology, clinical features, diagnosis, treatment, and management.
AB  - Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic
      Gram-positive bacteria that normally colonize the human mouth and digestive and
      genital tracts. Physicians must be aware of typical clinical presentations (such
      as cervicofacial actinomycosis following dental focus of infection, pelvic
      actinomycosis in women with an intrauterine device, and pulmonary actinomycosis
      in smokers with poor dental hygiene), but also that actinomycosis may mimic the
      malignancy process in various anatomical sites. Bacterial cultures and pathology
      are the cornerstone of diagnosis, but particular conditions are required in order
      to get the correct diagnosis. Prolonged bacterial cultures in anaerobic
      conditions are necessary to identify the bacterium and typical microscopic
      findings include necrosis with yellowish sulfur granules and filamentous Gram
      positive fungal-like pathogens. Patients with actinomycosis require prolonged (6-
      to 12-month) high doses (to facilitate the drug penetration in abscess and in
      infected tissues) of penicillin G or amoxicillin, but the duration of
      antimicrobial therapy could probably be shortened to 3 months in patients in whom
      optimal surgical resection of infected tissues has been performed. Preventive
      measures, such as reduction of alcohol abuse and improvement of dental hygiene,
      may limit occurrence of pulmonary, cervicofacial, and central nervous system
      actinomycosis. In women, intrauterine devices must be changed every 5 years in
      order to limit the occurrence of pelvic actinomycosis. 

PMID- 25045275
TI  - Relationship between insulin resistance and plasma vitamin D in adults.
AB  - A recent relationship between vitamin D deficiency and the risk of type 2
      diabetes mellitus (T2DM) and insulin resistance has been established through
      several studies. Research suggests a correlation between serum vitamin D and
      glycemic status measures. The aim of this study was to investigate the
      relationship between the plasma vitamin D levels (25[OH]D) and the factors linked
      to insulin resistance in a representative sample of Canadians ranging in age from
      16-79 years. Data were used from the Canadian Health Measures Survey where direct
      measures of health and wellness were reported from 1,928 subjects. These data
      were gathered from March 2007-February 2009 at 15 sites selected through a
      multistage sampling strategy. An inverse relationship between insulin resistance
      and plasma vitamin D level in both men and women was observed. This study
      provides additional evidence for the role of vitamin D in T2DM. If causally
      associated, the supplementation of vitamin D may help in preventing insulin
      resistance and subsequent T2DM. 

PMID- 25045277
TI  - Analysis of serum phosphate control and phosphate binder utilization in incident
      hemodialysis patients.
AB  - The purpose of this study was to conduct a retrospective analysis of serum
      phosphate level variability in patients new to hemodialysis (HD) and to identify
      patient characteristics associated with this variability. The medical records of
      47,742 incident HD patients attending US outpatient dialysis centers between
      January 1, 2006 and March 31, 2009 were analyzed. Monthly mean serum phosphate
      levels determined over a 6-month evaluation period (months 4-9 after HD
      initiation) were assigned to one of three strata: low (<1.13 mmol/L [<3.5
      mg/dL]); target (1.13-1.78 mmol/L [3.5-5.5 mg/dL]); or high (>1.78 mmol/L [>5.5
      mg/dL]). Patients were classified into one of six serum phosphate variability
      groups based on variability among monthly mean phosphate levels over the 6-month
      evaluation period: consistently target; consistently high; high-to-target; high
      to-low; target-to-low; or consistently low. Only 15% of patients (consistently
      target group) maintained monthly mean serum phosphate levels within the target
      range throughout the 6-month evaluation period. Age, Charlson comorbidity index,
      serum phosphate, and intact parathyroid hormone levels prior to HD initiation
      were strongly associated (P<0.001) with serum phosphate levels after HD
      initiation. Overall patient-reported phosphate binder usage increased from 35% at
      baseline to 52% at end of study. The low proportion of patients achieving target
      phosphate levels and low rates of phosphate binder usage observed during the
      study suggest that alternative strategies could be developed to control serum
      phosphate levels. Possible strategies that might be incorporated to help improve
      the management of hyperphosphatemia in incident HD patients include dietary
      modification, dialysis optimization, and earlier and sustained use of phosphate
      binders. 

PMID- 25045278
TI  - Vascular access for hemodialysis: current perspectives.
AB  - A well-functioning vascular access (VA) is a mainstay to perform an efficient
      hemodialysis (HD) procedure. There are three main types of access: native
      arteriovenous fistula (AVF), arteriovenous graft, and central venous catheter
      (CVC). AVF, described by Brescia and Cimino, remains the first choice for chronic
      HD. It is the best access for longevity and has the lowest association with
      morbidity and mortality, and for this reason AVF use is strongly recommended by
      guidelines from different countries. Once autogenous options have been exhausted,
      prosthetic fistulae become the second option of maintenance HD access
      alternatives. CVCs have become an important adjunct in maintaining patients on
      HD. The preferable locations for insertion are the internal jugular and femoral
      veins. The subclavian vein is considered the third choice because of the high
      risk of thrombosis. Complications associated with CVC insertion range from 5% to
      19%. Since an increasing number of patients have implanted pacemakers and
      defibrillators, usually inserted via the subclavian vein and superior vena cava
      into the right heart, a careful assessment of risk and benefits should be taken.
      Infection is responsible for the removal of about 30%-60% of HD CVCs, and
      hospitalization rates are higher among patients with CVCs than among AVF ones.
      Proper VA maintenance requires integration of different professionals to create a
      VA team. This team should include a nephrologist, radiologist, vascular surgeon,
      infectious disease consultant, and members of the dialysis staff. They should
      provide their experience in order to give the best options to uremic patients and
      the best care for their VA. 

PMID- 25045279
TI  - Targeting metastatic colorectal cancer - present and emerging treatment options.
AB  - Metastatic colorectal cancer is a significant cause of morbidity and mortality in
      the US and around the world. While several novel cytotoxic and biologic therapies
      have been developed and proven efficacious in the past two decades, their optimal
      use in terms of patient selection, drug combinations, and regimen sequences has
      yet to be defined. Recent investigations regarding anti-epidermal growth factor
      receptor therapies include the comparison of single-agent panitumumab and
      cetuximab, the benefit of adding cetuximab to chemotherapy in the conversion
      therapy setting, the comparison of cetuximab and bevacizumab when added to first
      line chemotherapy, and predictive biomarkers beyond KRAS exon 2 (codons 12 and
      13) mutations. With respect to anti-vascular endothelial growth factor therapies,
      new data on continuing bevacizumab beyond disease progression on a bevacizumab
      containing chemotherapy regimen, the addition of bevacizumab to triplet
      chemotherapy in the first-line setting, maintenance therapy with bevacizumab plus
      either capecitabine or erlotinib, the addition of aflibercept to chemotherapy,
      and regorafenib as monotherapy have emerged. Recent scientific and technologic
      advances in the field of metastatic colorectal cancer promise to elucidate the
      biological underpinnings of this disease and its therapies for the goal of
      improving personalized treatments for patients with metastatic colorectal cancer.

PMID- 25045276
TI  - Molecular pathways in non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change
      characterized by the accumulation of triglycerides in hepatocytes and has
      frequently been associated with obesity, type 2 diabetes mellitus,
      hyperlipidemia, and insulin resistance. It is an increasingly recognized
      condition that has become the most common liver disorder in developed countries,
      affecting over one-third of the population and is associated with increased
      cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders,
      beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis
      can evolve into non-alcoholic steatohepatitis, a medley of inflammation,
      hepatocellular injury, and fibrosis, often resulting in cirrhosis and even
      hepatocellular cancer. However, the molecular mechanism underlying NAFLD
      progression is not completely understood. Its pathogenesis has often been
      interpreted by the "double-hit" hypothesis. The primary insult or the "first hit"
      includes lipid accumulation in the liver, followed by a "second hit" in which
      proinflammatory mediators induce inflammation, hepatocellular injury, and
      fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and
      their metabolites may be the true lipotoxic agents that contribute to NAFLD
      progression; a multiple parallel hits hypothesis has also been suggested. In
      NAFLD patients, insulin resistance leads to hepatic steatosis via multiple
      mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been
      described that not only de novo FA synthesis is increased, but FAs are also taken
      up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and
      secretion of very-low-density lipoproteins has been reported. This review
      discusses the molecular mechanisms that underlie the pathophysiological changes
      of hepatic lipid metabolism that contribute to NAFLD. 

PMID- 25045280
TI  - Pharmacogenomic knowledge gaps and educational resource needs among physicians in
      selected specialties.
AB  - BACKGROUND: The use of pharmacogenomic testing in the clinical setting has the
      potential to improve the safety and effectiveness of drug therapy, yet studies
      have revealed that physicians lack knowledge about the topic of pharmacogenomics,
      and are not prepared to implement it in the clinical setting. This study further
      explores the pharmacogenomic knowledge deficit and educational resource needs
      among physicians. MATERIALS AND METHODS: Surveys of primary care physicians,
      cardiologists, and psychiatrists were conducted. RESULTS: Few physicians reported
      familiarity with the topic of pharmacogenomics, but more reported confidence in
      their knowledge about the influence of genetics on drug therapy. Only a small
      minority had undergone formal training in pharmacogenomics, and a majority
      reported being unsure what type of pharmacogenomic tests were appropriate to
      order for the clinical situation. Respondents indicated that an ideal
      pharmacogenomic educational resource should be electronic and include such
      components as how to interpret pharmacogenomic test results, recommendations for
      prescribing, population subgroups most likely to be affected, and contact
      information for laboratories offering pharmacogenomic testing. CONCLUSION:
      Physicians continue to demonstrate pharmacogenomic knowledge gaps, and are unsure
      about how to use pharmacogenomic testing in clinical practice. Educational
      resources that are clinically oriented and easily accessible are preferred by
      physicians, and may best support appropriate clinical implementation of
      pharmacogenomics.

PMID- 25045281
TI  - Lowering low-density lipoprotein cholesterol levels in patients with type 2
      diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin
      resistance, and/or progressive loss of beta-cell function. T2DM patients are at
      increased risk of micro- and macrovascular disease, and are often considered as
      representing an atherosclerotic coronary heart disease (CHD) risk equivalent.
      Interventions directed at glucose and lipid level control in T2DM patients may
      reduce micro- and macrovascular disease. The optimal T2DM agent is one that
      lowers glucose levels with limited risk for hypoglycemia, and with no clinical
      trial evidence of worsening CHD risk. Lipid-altering drugs should preferably
      reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have
      evidence that the mechanism of action reduces CHD risk. Statins reduce low
      density lipoprotein cholesterol and apo B and have evidence of improving CHD
      outcomes, and are thus first-line therapy for the treatment of
      hypercholesterolemia. In patients who do not achieve optimal lipid levels with
      statin therapy, or who are intolerant to statin therapy, add-on therapy or
      alternative therapies may be indicated. Additional available agents to treat
      hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates,
      niacin, and ezetimibe. This review discusses the use of these alternative agents
      to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in
      combination with statin therapy. 

PMID- 25045282
TI  - Costs of moderate to severe chronic pain in primary care patients - a study of
      the ACCORD Program.
AB  - BACKGROUND: The economic burden of chronic noncancer pain (CNCP) remains
      insufficiently documented in primary care. PURPOSE: To evaluate the annual direct
      health care costs and productivity costs associated with moderate to severe CNCP
      in primary care patients taking into account their pain disability. MATERIALS AND
      METHODS: Patients reporting noncancer pain for at least 6 months, at a pain
      intensity of 4 or more on a 0 (no pain) to 10 (worst possible pain) intensity
      scale, and at a frequency of at least 2 days a week, were recruited from
      community pharmacies. Patients' characteristics, health care utilization, and
      productivity losses (absenteeism and presenteeism) were documented using
      administrative databases, pharmacies' renewal charts, telephone, and self
      administered questionnaires. Patients were stratified by tertile of pain
      disability measured by the Brief Pain Inventory questionnaire. RESULTS: Patients
      (number =483) were, on average, 59 years old, mainly women (67.5%), and suffered
      from CNCP for a mean of 12 years at an average pain intensity of 6.5+/-1.9. The
      annual direct health care costs and productivity costs averaged CAD $9,565 (+/
      $13,993) and CAD $7,072 (+/-$11,716), respectively. The use of complementary
      health care services accounted for almost 50% of the direct health care costs.
      The mean adjusted total direct health care costs (considering pain-related
      hospitalizations only) and productivity costs increased with more pain
      disability: low disability, CAD $12,118; moderate, CAD $18,278; and severe, CAD
      $19,216; P=0.001. CONCLUSION: The economic burden of CNCP is substantial and
      increases with the level of pain disability, which suggests the need for and
      potential benefits of improving CNCP management through specific and adapted
      treatment plans targeting the impact of pain on daily functioning.

PMID- 25045283
TI  - Timing, Duration and Quality of sleep, and Level of Daytime sleepiness in 1166
      Retired seniors.
AB  - A telephone survey of 1166 community resident seniors (658 male, 508 female, age
      between 65 and 97 years, mean 74.8 years) was undertaken, which included among
      other components telephone versions of the Pittsburgh Sleep Quality Index (PSQI),
      the Epworth Sleepiness Scale (ESS), and the Sleep Timing Questionnaire (STQ). The
      median PSQI score was 5 and the median ESS score 6, suggesting that neither sleep
      problems, nor daytime sleepiness problems, were particularly prevalent in this
      sample of seniors. The STQ indicated that the habitual timing of the sleep
      episode appeared to be within the usual 11 pm to 7:30 am range, with about 7.5
      hours of actual sleep within that interval being reported. There was, however, a
      sizable minority who broke this pattern, with 25% of the sample reporting less
      than 6.7 hours of sleep, and problems with nocturnal sleep and daytime
      sleepiness.

PMID- 25045285
TI  - Improving the medical student experience using electronic timetabling.

PMID- 25045284
TI  - Androgen deprivation therapy for prostate cancer: long-term safety and patient
      outcomes.
AB  - Androgen deprivation therapy (ADT) constitutes the first-line treatment for
      patients with locally advanced tumors, recurrent or metastatic disease. Given its
      widespread use, clinicians should be familiar with common side effects of this
      treatment. This review focuses on common side effects of ADT and available
      treatment options to control the side effects. Also, it briefly compares
      continuous ADT with other therapeutic approaches for androgen deprivation in
      prostate cancer patients. Similar to hormonal medications, newer non-hormonal
      therapeutic options including gabapentin and acupuncture have at best moderate
      effect in controlling hot flashes in patients on ADT. Supervised and/or home
      exercise programs significantly improve ADT-related fatigue,
      metabolic/cardiovascular side effects, and cognitive dysfunction. Denosumab, a
      human monoclonal antibody against RANK-L, is more effective than bisphosphonates
      in preventing skeletal-related events in patients with metastatic or castrate
      resistant prostate cancer and unlike bisphosphonates, it can also reduce the risk
      of vertebral fractures in men receiving ADT for non-metastatic prostate cancer.
      Toremifene, a selective estrogen receptor inhibitor, has dual beneficial effects
      on ADT-related osteoporosis and metabolic dysfunction. Metformin coupled with
      lifestyle modification is also a well-tolerated treatment for metabolic changes
      during ADT. While producing similar oncological outcomes, intermittent ADT is
      associated with higher quality of life in patients under ADT by improving bone
      health, less metabolic and hematologic complications, and fewer hot flashes and
      sexual dysfunction events. 

PMID- 25045286
TI  - Diet, microbiota, and inflammatory bowel disease: lessons from Japanese foods.
AB  - The incidence and prevalence of inflammatory bowel diseases (IBDs) including
      ulcerative colitis and Crohn disease are rapidly increasing in Western countries
      and in developed Asian countries. Although biologic agents targeting the immune
      system have been effective in patients with IBD, cessation of treatment leads to
      relapse in the majority of patients, suggesting that intrinsic immune
      dysregulation is an effect, not a cause, of IBD. Dramatic changes in the
      environment, resulting in the dysregulated composition of intestinal microbiota
      or dysbiosis, may be associated with the fundamental causes of IBD. Japan now has
      upgraded water supply and sewerage systems, as well as dietary habits and
      antibiotic overuse that are similar to such features found in developed Western
      countries. The purpose of this review article was to describe the association of
      diet, particularly Japanese food and microbiota, with IBD. 

PMID- 25045288
TI  - Reflux esophagitis is one of highly prevalent comorbidities among patients with
      chronic obstructive pulmonary disease.

PMID- 25045287
TI  - Vitamin D and chronic kidney disease.
AB  - Chronic kidney disease (CKD) has been recognized as a significant global health
      problem because of the increased risk of total and cardiovascular morbidity and
      mortality. Vitamin D deficiency or insufficiency is common in patients with CKD,
      and serum levels of vitamin D appear to have an inverse correlation with kidney
      function. Growing evidence has indicated that vitamin D deficiency may contribute
      to deteriorating renal function, as well as increased morbidity and mortality in
      patients with CKD. Recent studies have suggested that treatment with active
      vitamin D or its analogues can ameliorate renal injury by reducing fibrosis,
      apoptosis, and inflammation in animal models; this treatment also decreases
      proteinuria and mortality in patients with CKD. These renoprotective effects of
      vitamin D treatment are far beyond its classical role in the maintenance of bone
      and mineral metabolism, in addition to its pleiotropic effects on extra-mineral
      metabolism. In this review, we discuss the altered metabolism of vitamin D in
      kidney disease, and the potential renoprotective mechanisms of vitamin D in
      experimental and clinical studies. In addition, issues regarding the effects of
      vitamin D treatment on clinical outcomes are discussed. 

PMID- 25045289
TI  - Can we more efficiently save patients with vitamin K-dependent coagulopathy
      caused by superwarfarin intoxication?

PMID- 25045290
TI  - Proper time to initiate antiosteoporotic treatment in rheumatoid arthritis with
      or without glucocorticoid use.

PMID- 25045291
TI  - Clinical outcomes of gastric variceal obliteration using N-butyl-2-cyanoacrylate
      in patients with acute gastric variceal hemorrhage.
AB  - BACKGROUND/AIMS: To evaluate the long-term efficacy and safety of endoscopic
      injection of N-butyl-2-cyanoacrylate (NBC; Histoacryl) for treatment of bleeding
      gastric varices. METHODS: We retrospectively analyzed the records of 455 patients
      with gastric variceal hemorrhage (GVH) who were consecutively treated with NBC
      from January 2004 to July 2013, with a mean follow-up period of 582 days. The
      patients' endoscopic findings, initial hemostasis, complications, rebleeding
      rates, and bleeding-related death rates were reviewed. RESULTS: Hemostasis was
      achieved initially in 96.9% (441/455) of patients; rebleeding occurred in 35.2%
      (160/455), and the bleeding-related death rate was 6.8% (31/455) during follow
      up. Complications included fever (6.8%), abdominal pain (3.7%), diarrhea (1.3%),
      spontaneous bacterial peritonitis (0.7%), bacteremia (0.4%), and embolism (0.2%).
      A red-color sign on concomitant esophageal varices (EVs) (p = 0.002) and previous
      history of variceal bleeding (p < 0.001) were significant risk factors for
      rebleeding within 1 year. The Child-Pugh score (p < 0.001), presence of
      hepatocellular carcinoma (p = 0.001), and failure of initial hemostasis (p <
      0.001) were the risk factors most closely associated with bleeding-related death.
      CONCLUSIONS: This study provides a comprehensive overview of the outcomes and
      prognostic factors of patients with GVH. The results may help in the selection of
      effective treatment strategies for patients with GVH.

PMID- 25045292
TI  - Effect of anemia correction on left ventricular structure and filling pressure in
      anemic patients without overt heart disease.
AB  - BACKGROUND/AIMS: There are few data on the effects of low hemoglobin levels on
      the left ventricle (LV) in patients without heart disease. The objective of this
      study was to document changes in the echocardiographic variables of LV structure
      and function after the correction of anemia without significant cardiovascular
      disease. METHODS: In total, 34 iron-deficiency anemia patients (35 +/- 11 years
      old, 32 females) without traditional cardiovascular risk factors or
      cardiovascular disease and 34 age- and gender-matched controls were studied.
      Assessments included history, physical examination, and echocardiography. Of the
      34 patients with anemia enrolled, 20 were followed and underwent echocardiography
      after correction of the anemia. RESULTS: There were significant differences
      between the anemia and control groups in LV diameter, left ventricular mass index
      (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E)
      velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral
      to mitral annular early diastolic velocity (E/E'), stroke volume, and cardiac
      index. Twenty patients underwent follow-up echocardiography after treatment of
      anemia. The follow-up results showed significant decreases in the LV end
      diastolic and end-systolic diameters and LVMI, compared with baseline levels.
      LAVI, E velocity, and E/E' also decreased, suggesting a decrease in LV filling
      pressure. CONCLUSIONS: Low hemoglobin level was associated with larger cardiac
      chambers, increased LV, mass and higher LV filling pressure even in the subjects
      without cardiovascular risk factors or overt cardiovascular disease. Appropriate
      correction of anemia decreased LV mass, LA volume, and E/E'.

PMID- 25045293
TI  - Prediction of infarct severity from triiodothyronine levels in patients with ST
      elevation myocardial infarction.
AB  - BACKGROUND/AIMS: The aim of the present study was to evaluate the relationship
      between thyroid hormone levels and infarct severity in patients with ST-elevation
      myocardial infarction (STEMI). METHODS: We retrospectively reviewed thyroid
      hormone levels, infarct severity, and the extent of transmurality in 40 STEMI
      patients evaluated via contrast-enhanced cardiac magnetic resonance imaging.
      RESULTS: The high triiodothyronine (T3) group (>= 68.3 ng/dL) exhibited a
      significantly higher extent of transmural involvement (late transmural
      enhancement > 75% after administration of gadolinium contrast agent) than did the
      low T3 group (60% vs. 15%; p = 0.003). However, no significant difference was
      evident between the high- and low-thyroid-stimulating hormone/free thyroxine
      (FT4) groups. When the T3 cutoff level was set to 68.3 ng/dL using a receiver
      operating characteristic curve, the sensitivity was 80% and the specificity 68%
      in terms of differentiating between those with and without transmural
      involvement. Upon logistic regression analysis, high T3 level was an independent
      predictor of transmural involvement after adjustment for the presence of diabetes
      mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62;
      95% confidence interval, 3.29 to 502; p = 0.004). CONCLUSIONS: The T3 level
      predicted transmural involvement that was independent of glycoprotein IIb/IIIa
      inhibitor use and DM positivity.

PMID- 25045294
TI  - Prevalence and risk factors for reflux esophagitis in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND/AIMS: Gastroesophageal reflux disease is one of the most common causes
      of chronic cough and is a potential risk factor for the exacerbation of chronic
      obstructive pulmonary disease (COPD). The aim of this study was to investigate
      the prevalence and risk factors for reflux esophagitis (RE) in COPD patients.
      METHODS: From our hospital database, between September 2006 and April 2010, we
      searched for subjects who were 40 years old or older and had undergone both
      postbronchodilator spirometry and esophagogastroduodenoscopy (EGD). COPD was
      defined as having a ratio of forced expiratory volume in 1 second to forced vital
      capacity < 0.7 in postbronchodilator spirometry and no abnormality causing airway
      obstruction, except emphysematous changes, on a chest X-ray. The diagnosis of RE
      was based on a mucosal break surrounding the distal esophageal sphincter through
      EGD. RESULTS: In total, 253 patients with COPD were enrolled. The prevalence of
      RE in COPD was 30% (76/253). Multiple logistic regression analyses revealed that
      age (odds ratio [OR], 0.950; 95% confidence interval [CI], 0.918 to 0.983; p =
      0.003), smoking pack-years (OR, 1.015; 95% CI, 1.004 to 1.025; p = 0.006), and
      inhaled anticholinergics (OR, 0.516; 95% CI, 0.271 to 0.982; p = 0.044) were
      independently associated with RE in COPD patients. CONCLUSIONS: The prevalence of
      RE in our COPD patients was higher than that reported previously in the Korean
      general population. In COPD, smoking increased the risk of RE, whereas inhaled
      anticholinergics may be associated with a reduced risk of RE.

PMID- 25045296
TI  - Effects of pretransplant plasmapheresis and rituximab on recurrence of focal
      segmental glomerulosclerosis in adult renal transplant recipients.
AB  - BACKGROUND/AIMS: Recurrent focal segmental glomerulosclerosis (FSGS) following
      renal transplantation is relatively common. However, the risk factors and optimal
      pretransplant treatment preventing recurrence of FSGS remain controversial.
      METHODS: We retrospectively reviewed 27 adult renal transplant recipients with
      FSGS over a period of 10 years. We first compared possible risk factors for FSGS
      recurrence between the recurrence and nonrecurrence groups. Then we evaluated the
      effect of pretransplant plasmapheresis (PP; n = 4) and PP with rituximab (PP +
      RTX; n = 5) on recurrence of FSGS after transplantation compared to control
      patients that were not treated with these modalities. RESULTS: There were seven
      recurrences in 27 patients (25.9%), but there were no significant differences in
      possible risk factors for FSGS recurrence between the two groups. Recurrence
      rates between patients with pretransplant PP or PP + RTX and control patients
      were not significantly different (22.2% vs. 27.7%, p > 0.05). There was also no
      significant difference in recurrence between the pretransplant PP and PP + RTX
      groups (25% vs. 20%, p > 0.05). CONCLUSIONS: Pretransplant PP or PP + RTX do not
      significantly decrease the recurrence of FSGS in adult renal transplant
      candidates.

PMID- 25045295
TI  - The effect of 5-aminoimidazole-4-carboxamide-ribonucleoside was mediated by p38
      mitogen activated protein kinase signaling pathway in FRO thyroid cancer cells.
AB  - BACKGROUND/AIMS: 5'-Adenosine monophosphate (AMP)-activated protein kinase (AMPK)
      is a cellular energy sensor that monitors intracellular AMP/adenosine
      triphosphate (ATP) ratios and is a key regulator of the proliferation and
      survival of diverse malignant cell types. In the present study, we investigated
      the effect of activating AMPK by 5-aminoimidazole-4-carboxamide-ribonucleotide
      (AICAR) in thyroid cancer cells. METHODS: We used FRO thyroid cancer cells
      harboring the BRAF(V600E) mutation to examine the effect of AICAR on cell
      proliferation and cell survival. We also evaluated the involvement of mitogen
      activated protein kinase (MAPK) pathways in this effect. RESULTS: We found that
      AICAR treatment promoted AMPK activation and suppressed cell proliferation and
      survival by inducing p21 accumulation and activating caspase-3. AICAR
      significantly induced activation of p38 MAPK, and pretreatment with SB203580, a
      specific inhibitor of the p38 MAPK pathway, partially but significantly rescued
      cell survival. Furthermore, small interfering RNA targeting AMPK-alpha1 abolished
      AICAR-induced activation of p38 MAPK, p21 accumulation, and activation of caspase
      3. CONCLUSIONS: Our findings demonstrate that AMPK activation using AICAR
      inhibited cell proliferation and survival by activating p38 MAPK and proapoptotic
      molecules in FRO thyroid cancer cells. These results suggest that the AMPK and
      p38 MAPK signaling pathways may be useful therapeutic targets to treat thyroid
      cancer.

PMID- 25045297
TI  - Ferritin as a predictor of decline in residual renal function in peritoneal
      dialysis patients.
AB  - BACKGROUND/AIMS:  AIMS: Inflammation is an important factor in renal injury.
      Ferritin, an inflammatory marker, is considered an independent predictor of rapid
      renal progression in patients with chronic kidney disease. However, the
      relationship between ferritin and residual renal function (RRF) in patients
      undergoing peritoneal dialysis (PD) remains unclear. METHODS: We reviewed the
      medical records of patients who started PD between June 2001 and March 2012 at
      Soonchunhyang University Bucheon Hospital, Korea. A total of 123 patients were
      enrolled in the study. At 1 month after the initiation of PD, RRF was determined
      by a 24-hour urine collection and measured every 6 months thereafter. Clinical
      and biochemical data at the time of the initial 24-hour urine collection were
      considered as baseline. RESULTS: The RRF reduction rate was significantly greater
      in patients with high ferritin (ferritin >= 250 ng/mL) compared with those with
      low ferritin (ferritin < 250 ng/mL; -1.71 +/- 1.36 mL/min/yr/1.73 m(2) vs. -0.84
      +/- 1.63 mL/min/yr/1.73 m(2), respectively; p = 0.007). Pearson correlation
      analysis revealed a significant negative correlation between the baseline serum
      ferritin level and the RRF reduction rate (r = -0.219, p = 0.015). Using multiple
      linear regression analysis and adjusting for other risk factors, baseline serum
      ferritin was an independent factor for the RRF reduction rate (beta = -0.002, p =
      0.002). CONCLUSIONS: In this study we showed that a higher ferritin level was
      significantly associated with a more rapid RRF decline in patients undergoing PD.

PMID- 25045298
TI  - Evaluation of risk factors in patients with vitamin K-dependent coagulopathy
      presumed to be caused by exposure to brodifacoum.
AB  - BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of
      unknown origin have been reported. Such patients lack any relevant family history
      and have no systemic disease, raising suspicion of superwarfarin intoxication. We
      evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms
      in patients with suspected superwarfarin intoxication. In addition, we determined
      how to effectively treat vitamin K-dependent coagulopathy caused by suspected
      superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin
      intoxication who lacked any definitive history of rodenticide ingestion were
      included. Thirty-one patients initially diagnosed with rodenticide poisoning were
      also included. We performed a retrospective chart review of all subjects and
      examined clinical data including patient demographics and medical histories.
      RESULTS: Patients initially diagnosed with rodenticide poisoning were divided
      into two groups, one of which had a laboratory abnormality (prothrombin time [PT]
      > 13 seconds) and another group with PTs in the normal range. There was no
      significant difference between the two groups in any of age, gender, the extent
      of chronic alcohol consumption, the causative rodenticide, psychiatric problems,
      ingestion of drugs interacting with warfarin, the extent of intoxication, or the
      type of ingestion attempt. The albumin level of the former group was
      significantly lower than that of the latter group (p = 0.014). Furthermore, a
      significant difference between the two groups was evident in terms of
      simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most
      patients with superwarfarin poisoning did not exhibit any complication. When such
      complications were evident, they were associated with serum albumin level and
      coingestion of rodenticide and alcohol.

PMID- 25045300
TI  - Resting energy expenditure is not associated with disease activity in women with
      rheumatoid arthritis: cross-sectional study.
AB  - BACKGROUND/AIMS: Increased resting energy expenditure (REE) in rheumatoid
      arthritis (RA) patients is thought to be caused by hypermetabolism associated
      with production of proinflammatory cytokines. Our aim in the present study was to
      explore the possible association between REE and disease activity in females with
      RA. METHODS: A total of 499 female RA patients were recruited to this cross
      sectional study assessing REE scores on disease activity indices (the routine
      assessment of patient index data 3 [RAPID3], the disease activity score 28, and
      the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA
      associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide
      [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also
      enrolled. RESULTS: REE did not differ between RA patients (all patients, and
      those in remission or not) and controls, or between RA patients in remission or
      not (p > 0.05 for all comparisons). Increased REE in total RA patients was
      associated with younger age and a higher body mass index (BMI) (p < 0.001 and p <
      0.001, respectively), but not with disease activity index scores on any of
      RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a
      significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of
      disease duration, functional status, or anti-CCP antibody titer in RA patients
      was significantly related to REE, based on analysis of covariance. CONCLUSIONS:
      We found no association between REE and disease activity in RA patients, implying
      that energy metabolism in RA patients might be independent of RA-associated
      systemic inflammation.

PMID- 25045299
TI  - Are glucocorticoid-induced osteoporosis recommendations sufficient to determine
      antiosteoporotic treatment for patients with rheumatoid arthritis?
AB  - BACKGROUND/AIMS: We investigated differences in identifying candidates for
      antiosteoporotic treatment in rheumatoid arthritis (RA) patients according to two
      available clinical guidelines. METHODS: We prospectively enrolled 100 female
      patients aged 50 years or older with RA who visited Hanyang University Hospital
      for periodic examinations between April 2011 and August 2011. We applied the
      glucocorticoid-induced osteoporosis (GIOP) recommendations and the National
      Osteoporosis Foundation (NOF) guidelines to RA patients and examined agreement
      between the guidelines for identifying candidates for antiosteoporotic treatment.
      We also analyzed the impact of screening vertebral fractures (VFs) in determining
      the treatment of osteoporosis in RA patients. RESULTS: The 57 patients taking
      glucocorticoids were classified into high-risk (n = 23), medium-risk (n = 16),
      and low-risk (n = 18) groups according to the GIOP recommendations. Based on the
      NOF guidelines, 36 of 57 patients were candidates for antiosteoporotic treatment
      and the agreement between two guidelines was high (kappa = 0.76). Two of the 18
      patients in the low-risk group and 19 of 43 patients not eligible per the GIOP
      recommendations were classified as candidates for antiosteoporotic treatment by
      the NOF guidelines. CONCLUSIONS: In determining antiosteoporotic treatment for RA
      patients, using only the GIOP recommendations is insufficient. Application of the
      NOF guidelines in patients not eligible for or classified into the low-risk group
      per the GIOP recommendations and screening for VFs may be helpful in deciding on
      antiosteoporotic treatment in RA patients.

PMID- 25045301
TI  - A case of myocardial involvement in lung cancer that mimics ST segment elevation
      in myocardial infarction.

PMID- 25045302
TI  - Acute right heart failure caused by iatrogenic brachiocephalic arteriovenous
      fistula following orthopedic surgery.

PMID- 25045303
TI  - Recurrent neutropenia induced by rifabutin in a renal transplant recipient.

PMID- 25045304
TI  - Subcutaneous sarcoidosis presenting as a suprapubic mass, acute kidney injury,
      and hypercalcemia.

PMID- 25045305
TI  - Successful treatment with clarithromycin for patients with polymyalgia
      rheumatica.

PMID- 25045306
TI  - Upper thoracic vertebral abnormalities in a patient with rheumatoid arthritis.

PMID- 25045307
TI  - Carpal tunnel syndrome caused by tophaceous gout.

PMID- 25045309
TI  - FRACTIONAL WAVE EQUATIONS WITH ATTENUATION.
AB  - Fractional wave equations with attenuation have been proposed by Caputo [5],
      Szabo [27], Chen and Holm [7], and Kelly et al. [11]. These equations capture the
      power-law attenuation with frequency observed in many experimental settings when
      sound waves travel through inhomogeneous media. In particular, these models are
      useful for medical ultrasound. This paper develops stochastic solutions and weak
      solutions to the power law wave equation of Kelly et al. [11].

PMID- 25045310
TI  - Effects of Bifidobacterium bifidum G9-1 on Nasal Symptoms in a Guinea Pig Model
      of Experimental Allergic Rhinitis.
AB  - Recent studies of several animal models have shown beneficial effects of
      probiotics against allergic responses. However, few reports have examined the
      effects of probiotics on allergic nasal symptoms such as sneezing and nasal
      obstruction in animal models of allergic rhinitis. This study evaluated the
      efficacy of Bifidobacterium bifidum G9-1 (BBG9-1) on antigen-induced nasal
      symptoms using guinea pig models of allergic rhinitis. Oral administration of
      BBG9-1 significantly inhibited antigen-induced allergic nasal reactions such as
      sneezing and nasal obstruction. Our results suggest that BBG9-1 may be useful for
      alleviating nasal symptoms in patients with allergic rhinitis. 

PMID- 25045311
TI  - Influence of Lactobacillus pentosus S-PT84 Ingestion on the Mucosal Immunity of
      Healthy and Salmonella Typhimurium-Infected Mice.
AB  - Lactobacillus pentosus (L. pentosus) strain S-PT84, isolated from Kyoto pickles,
      enhances splenic natural killer (NK) cell activity, and has high T-helper1 (Th1)
      cytokine and type 1-IFN (IFN-alpha) inducing activity. In the present study, we
      investigated the influence of S-PT84 ingestion on the mucosal immunity of healthy
      and Salmonella Typhimurium (S. Typhimurium)-infected mice. In the S. Typhimurium
      infection model, numbers of S. Typhimurium in feces and the spleen were
      significantly decreased, and body weight loss and deterioration in the general
      health score of S. Typhimurium-infected mice were improved by S-PT84 ingestion.
      Oral administration of S-PT84 enhanced IL-5 and IL-6 production from Peyer's
      patch cells in vitro, with a concomitant significant increase in IgA production
      from Peyer's patch cells, which may explain the mechanism of enhanced IgA
      production in the small intestine in vivo. These results suggest that S-PT84
      ingestion is useful for the maintenance of health or the improvement of certain
      symptoms during pathogen infection. 

PMID- 25045312
TI  - Establishment and Evaluation of an in vitro M Cell Model using C2BBe1 Cells and
      Raji Cells.
AB  - In vitro M cell models, consisting of co-cultures of Caco-2 cells and lymphoid
      cells, were developed and examined to observe bacterial transport. However, under
      our experimental conditions, the differentiation of Caco-2 cells into M cell-like
      cells could not be induced efficiently. To obtain a functionally stable M cell
      model based on human cells, C2BBe1 cells were screened and co-cultured with human
      Raji cells. In our co-cultures, increased sialyl Lewis A antigen expression and
      decreased Ulex europeaus agglutinin 1 binding were observed. Regarding the
      functional properties of the model, microsphere and lactic acid bacteria
      transport across the C2BBe1 co-cultures were increased compared with the levels
      seen in monocultures. The C2BBe1 monolayers that were co-cultured with Raji cells
      exhibited some M cell features; therefore, we consider our M cell model to be
      useful for investigating the interactions of bacteria with M cells. 

PMID- 25045313
TI  - Dihydrodaidzein-producing Clostridium-like intestinal bacterium, strain TM-40,
      affects in vitro metabolism of daidzein by fecal microbiota of human male equol
      producer and non-producers.
AB  - Much attention has been focused on the biological effects of equol, a metabolite
      of daidzein produced by intestinal microbiota. However, little is known about the
      role of isoflavone metabolizing bacteria in the intestinal microbiota. Recently,
      we isolated a dihydrodaidzein (DHD)-producing Clostridium-like bacterium, strain
      TM-40, from human feces. We investigated the effects of strain TM-40 on in vitro
      daidzein metabolism by human fecal microbiota from a male equol producer and two
      male equol non-producers. In the fecal suspension from the male equol non
      producer and DHD producer, DHD was detected in the in vitro fecal incubation of
      daidzein after addition of TM-40. The DHD concentration increased as the
      concentration of strain TM-40 increased. In the fecal suspension from the equol
      producer, the fecal equol production was increased by the addition of strain TM
      40. The occupation ratios of Bifidobacterium and Lactobacillales were higher in
      the equol non-producers than in the equol producer. Adding isoflavone
      metabolizing bacteria to the fecal microbiota should facilitate the estimation of
      the metabolism of isoflavonoids by fecal microbiota. Studies on the interactions
      among equol-producing microbiota and DHD-producing bacteria might lead to
      clarification of some of the mechanisms regulating the production of equol by
      fecal microbiota. 

PMID- 25045314
TI  - Development of recombinant vaccines in lactobacilli for elimination of
      salmonella.
AB  - Many Lactobacillus and Lactococcus strains are generally regarded as safe for
      consumption because they are utilized for food fermentation or inhabit the
      intestinal mucosa as commensals. Recently, vaccine delivery systems using lactic
      acid bacteria (LAB) have been under development. Our research group has been
      investigating the development of oral mucosal vaccines against Salmonella
      enterica serovar Enteritidis (SE) using Lactobacillus casei IGM393 as an antigen
      delivery vehicle. Recombinant lactobacilli expressing SE antigens, FliC, SipC,
      and OmpC, have been constructed and orally administered to mice. Antigen specific
      immune responses and protective immunity were elicited after the immunization.
      For adjuvant-delivery, IL-1beta-secreting L. casei was also engineered and its
      effects evaluated in vitro and in vivo. This article reviews a novel approach to
      the elimination of Salmonella via the development of a vaccine in lactobacilli. 

PMID- 25045315
TI  - Electrophysiological analysis of the mechanism of autonomic action by
      lactobacilli.
AB  - Autonomic nerves, consisting of both sympathetic and parasympathetic nerves,
      regulate various bodily functions such as blood pressure, body temperature,
      glucose metabolism, energy metabolism, and digestion. Our studies in rats and
      mice have demonstrated that food, flavor, and music affect physiological
      phenomena via changes in autonomic neurotransmissions. Intestinal injection of
      Lactobacillus johnsonii La1 (NCC533) suppressed sympathetic nerves that innervate
      the adrenal gland and kidney of urethane-anesthetized rats, lowering blood
      glucose and blood pressure levels, and excited the gastric parasympathetic nerve,
      elevating appetite and body weight. In contrast, intestinal injection of
      Lactobacillus paracasei ST11 (NCC2461) excited sympathetic nerves that innervate
      white and brown fat and the adrenal gland, increasing lipolysis and body
      temperature, and suppressed the gastric parasympathetic nerve, reducing appetite
      and body weight. Interestingly, we found that the hypothalamic suprachiasmatic
      nucleus (SCN), a master circadian clock, and histamine receptors in histaminergic
      neurons play important roles in peripheral autonomic control. To investigate the
      possible role of SCN and histamine receptors in lactobacilli-mediated pathology,
      we created an SCN-lesion model and experimented with histaminergic blocker
      injections. SCN lesion or injection of thioperamide, a histamine H3-receptor
      antagonist, eliminated the suppression of renal sympathetic nerve activity by
      NCC533, preventing blood pressure decline, and inhibited the enhancement of the
      gastric parasympathetic nerve induced by NCC533. In addition, diphenhydramine, a
      histamine H1-receptor antagonist, abolished the increases in renal sympathetic
      nerve activity and blood pressure caused by NCC2461. Infradiaphragmatic vagotomy
      eliminated the suppression of renal sympathetic nerve activity by NCC533, but did
      not affect the excitation of the renal sympathetic nerve by NCC2461.
      Collectively, these findings strongly suggest that SCN and histamine neurons are
      involved in the lactobacilli-mediated pathology of autonomic nerves and related
      physiological changes through abdominal afferent vagal pathway input to the
      central nervous system. 

PMID- 25045316
TI  - Intestinal microbiota and health in childhood.
AB  - Western medicine has only recently discovered that the intestinal microbiota is a
      major determinant of the well-being of the host. Although it would be
      oversimplifying to limit the benefits of breastfeeding compared to cow milk based
      infant formula to differences in gastrointestinal flora, the impact of the latter
      has been demonstrated beyond doubt. As a consequence, gastro intestinal flora
      manipulation with pre- and probiotics added to infant formula or food (mainly
      milk based products) and/or with food supplements have become a priority area of
      high quality research. The composition of intestinal microbiota can be
      manipulated with "biotics": antibiotics, prebiotics and probiotics.
      Commercialised pre- and probiotic products differ in composition and dose. Major
      threats to the concept of developing a major role for intestinal microbiota
      manipulation on health are the commercialisation of products claiming health
      benefits that have not been validated. Legislation of food supplements and
      medication differs substantially and allows commercialisation of poor quality
      food supplements, what will result in negative experiences. Medicinal products
      can only be advertised for which there is scientific proof of benefit that has
      been demonstrated with "the same product with the same dose in the same
      indication". Specificity of prebiotics and probiotics strains and product
      specificity are of importance, although high quality evidence for this assertion
      is missing. Dose-efficacy studies are urgently needed. Probiotics are "generally
      regarded as safe", but side effects such as septicemia and fungemia have
      sometimes been reported in high-risk situations. 

PMID- 25045317
TI  - Probiotics in the treatment and prevention of allergies in children.
AB  - Several studies on the pathogenesis of allergy both in man and experimental
      animals continue to show the importance of commensal bacteria in the
      gastrointestinal tract in stimulating and directing the immune system. The
      interest in modulating commensal bacteria flora with pre- and probiotics to
      prevent and treat food allergy has multiplied in recent years. We recently
      studied 230 infants with atopic dermatitis and suspected cow's milk allergy. The
      infants were randomly allocated to groups which received Lactobacillus GG (LGG),
      a mixture of four probiotic strains (MIX) or placebo for 4 weeks. We inferred
      that probiotics induce systemically detectable low-grade inflammation, which may
      explain the clinical effects and the secretion pattern of cytokines induced by
      PBMC. To study the ability of probiotics to prevent allergy in children, we
      recruited 1223 pregnant women carrying fetuses at increased risk of allergy for a
      double-blind placebo-controlled trial. Mothers used a mixture of four probiotic
      bacteria or a placebo from the 36th week of gestation. Their infants received the
      same probiotics plus prebiotic galacto-oligosaccharides for 6 months. At the 2
      year follow-up, a total of 925 infants participated. The cumulative incidence of
      allergic disease did not differ significantly between the synbiotic and the
      placebo group. However, synbiotics significantly reduced eczema. The preventive
      effect of synbiotics was more pronounced against IgE-associated diseases. At the
      5 year follow-up, 891(88%) of the 1018 intention-to-treat infants attended. In
      the probiotic and placebo groups, frequencies of allergic symptoms and IgE
      associated allergic disease and sensitization were similar, and the frequencies
      of eczema did not differ between the groups. Atopic eczema, allergic rhinitis and
      asthma appeared equal frequency in the groups. However, less IgE-associated
      allergic disease occurred in the cesarean-delivered infants given probiotics. In
      cesarean-delivered childen, we noticed a delayed rise in bifidobacteria recovery
      in placebo-treated children which was corrected by pro- and prebiotic
      supplementation. Indications from studies of feces and blood at the age 6 months
      suggest that probiotics may enhance both inflammation and immune defence of the
      gut. The probiotic treatment further stimulated maturation of the immune system
      since the infants given probiotics showed increased resistance to respiratory
      infections and improved vaccine antibody responses. 

PMID- 25045318
TI  - Early probiotic supplementation for the prevention of atopic disease in newborns
      probiotics and the hygiene hypothesis-.
AB  - Environmental factors during early infancy could theoretically affect immune
      system development and subsequent risk of allergic disease. One potentially
      helpful exposure is early infant supplementation with specific probiotic strains.
      Unlike other exposures, probiotic supplementation is feasible and has a good
      safety profile. A review of recent randomized, controlled trials suggests that
      the effect of supplementation with probiotics on preventing the development of
      allergic disease is mixed. Further studies are needed to define potential
      mechanisms of action, such as effects on infant microbiota, as well as potential
      subgroups of patients that may benefit from these interventions. 

PMID- 25045319
TI  - Metabolism of Isoflavones Found in the Pueraria thomsonii Flower by Human
      Intestinal Microbiota.
AB  - Isoflavones contained in the root and flower of Kudzu (Pueraria lobata and
      related species) are suggested to be the critical component for its effects.
      Although metabolism of soy isoflavones has been well studied, the composition of
      isoflavones found in Kudzu is completely different from that of soy isoflavones.
      In the present study, we investigated whether isoflavones found in the flower of
      Pueraria thomsonii, a species of Kudzu, were metabolized by human fecal
      microbiota and murine small intestinal enzymes. Among 5 glycosidic isoflavones of
      the Pueraria thomsonii flower, tectorigenin 7-O-xylosylglucoside, tectoridin,
      genistin and glycitin were completely hydrolyzed by a homogenate of germfree
      mouse small intestine without contribution of bacteria. Released aglycones were
      not further metabolized, except that up to half of glycitein disappeared. Mouse
      small intestinal enzymes did not metabolize 6-hydroxygenistein 6,7-di-O
      glucoside. Isoflavone aglycones as well as 6-hydroxygenistein 6,7-di-O-glucoside
      were highly metabolized by most of the human fecal suspensions. Metabolites were
      not detected with the present analytical methods in most cases. Although further
      investigations of the pharmacokinetics of Pueraria thomsonii flower isoflavones
      are needed, the results of the present study indicate active metabolism of
      Pueraria thomsonii flower isoflavones in the human intestine. 

PMID- 25045320
TI  - An Approach to the Synthesis of Functionalized Polycyclic Aromatic Hydrocarbons.
AB  - The application of a new benzannulation reaction for the regiocontrolled
      synthesis of functionalized chrysenes is reported. The initial benzannulation and
      the subsequent halogen displacement reactions are both highly regiospecific,
      which thereby enables the regiocontrolled synthesis of a variety of 4,10
      disubstituted chrysenes from commercially available 1,5-dihydroxynaphthalene.

PMID- 25045321
TI  - Adsorption of dissolved aluminum on sapphire-c and kaolinite: implications for
      points of zero charge of clay minerals.
AB  - We have studied the impact of dissolved aluminum on interfacial properties of two
      aluminum bearing minerals, corundum and kaolinite. The effect of intentionally
      adding dissolved aluminum on electrokinetic potential of basal plane surfaces of
      sapphire was studied by streaming potential measurements as a function of pH and
      was complemented by a second harmonic generation (SHG) study at pH 6. The
      electrokinetic data show a similar trend as the SHG data, suggesting that the SHG
      electric field correlates to zeta-potential. A comparable study was carried out
      on kaolinite particles. In this case electrophoretic mobility was measured as a
      function of pH. In both systems the addition of dissolved aluminum caused
      significant changes in the charging behavior. The isoelectric point consistently
      shifted to higher pH values, the extent of the shift depending on the amount of
      aluminum present or added. The experimental results imply that published
      isoelectric points of clay minerals may have been affected by this phenomenon.
      The presence of dissolved aluminum in experimental studies may be caused by
      particular pre-treatment methods (such as washing in acids and subsequent
      adsorption of dissolved aluminum) or even simply by starting a series of
      measurements from extreme pH (causing dissolution), and subsequently varying the
      pH in the very same batch. This results in interactions of dissolved aluminum
      with the target surface. A possible interpretation of the experimental results
      could be that at low aluminum concentrations adatoms of aluminum (we will refer
      to adsorbed mineral constituents as adatoms) can form at the sapphire basal
      plane, which can be rather easily removed. Simultaneously, once the surface has
      been exposed to sufficiently high aluminum concentration, a visible change of the
      surface is seen by AFM which is attributed to a surface precipitate that cannot
      be removed under the conditions employed in the current study. In conclusion,
      whenever pre-treatment or the starting point of an experiment favor the
      dissolution of aluminum, dissolved Al may remain in the experimental system and
      interact with the target surfaces. The systems are then no longer pristine and
      points of zero charge or sorption data are those of aluminum-bearing systems. 

PMID- 25045323
TI  - Comparability of HbA1c and lipids measured with dried blood spot versus venous
      samples: a systematic review and meta-analysis.
AB  - BACKGROUND: Levels of haemoglobin A1c (HbA1c) and blood lipids are important
      determinants of risk in patients with diabetes. Standard analysis methods based
      upon venous blood samples can be logistically challenging in resource-poor
      settings where much of the diabetes epidemic is occurring. Dried blood spots
      (DBS) provide a simple alternative method for sample collection but the
      comparability of data from analyses based on DBS is not well established.
      METHODS: We conducted a systematic review and meta-analysis to define the
      association of findings for HbA1c and blood lipids for analyses based upon
      standard methods compared to DBS. The Cochrane, Embase and Medline databases were
      searched for relevant reports and summary regression lines were estimated.
      RESULTS: 705 abstracts were found by the initial electronic search with 6 further
      reports identified by manual review of the full papers. 16 studies provided data
      for one or more outcomes of interest. There was a close agreement between the
      results for HbA1c assays based on venous and DBS samples (DBS = 0.9858venous +
      0.3809), except for assays based upon affinity chromatography. Significant
      adjustment was required for assays of total cholesterol (DBS = 0.6807venous +
      1.151) but results for triglycerides (DBS = 0.9557venous + 0.1427) were directly
      comparable. CONCLUSIONS: For HbA1c and selected blood lipids, assays based on DBS
      samples are clearly associated with assays based on standard venous samples.
      There are, however, significant uncertainties about the nature of these
      associations and there is a need for standardisation of the sample collection,
      transportation, storage and analysis methods before the technique can be
      considered mainstream. This should be a research priority because better
      elucidation of metabolic risks in resource poor settings, where venous sampling
      is infeasible, will be key to addressing the global epidemic of cardiovascular
      diseases.

PMID- 25045322
TI  - Bird Migration and Avian Influenza: A Comparison of Hydrogen Stable Isotopes and
      Satellite Tracking Methods.
AB  - Satellite-based tracking of migratory waterfowl is an important tool for
      understanding the potential role of wild birds in the long-distance transmission
      of highly pathogenic avian influenza. However, employing this technique on a
      continental scale is prohibitively expensive. This study explores the utility of
      stable isotope ratios in feathers in examining both the distances traveled by
      migratory birds and variation in migration behavior. We compared the satellite
      derived movement data of 22 ducks from 8 species captured at wintering areas in
      Bangladesh, Turkey, and Hong Kong with deuterium ratios (deltaD) of these and
      other individuals captured at the same locations. We derived likely molting
      locations from the satellite tracking data and generated expected isotope ratios
      based on an interpolated map of deltaD in rainwater. Although deltaD was
      correlated with the distance between wintering and molting locations,
      surprisingly, measured deltaD values were not correlated with either expected
      values or latitudes of molting sites. However, population-level parameters
      derived from the satellite-tracking data, such as mean distance between wintering
      and molting locations and variation in migration distance, were reflected by
      means and variation of the stable isotope values. Our findings call into question
      the relevance of the rainfall isotope map for Asia for linking feather isotopes
      to molting locations, and underscore the need for extensive ground truthing in
      the form of feather-based isoscapes. Nevertheless, stable isotopes from feathers
      could inform disease models by characterizing the degree to which regional
      breeding populations interact at common wintering locations. Feather isotopes
      also could aid in surveying wintering locations to determine where high
      resolution tracking techniques (e.g. satellite tracking) could most effectively
      be employed. Moreover, intrinsic markers such as stable isotopes offer the only
      means of inferring movement information from birds that have died as a result of
      infection. In the absence of feather based-isoscapes, we recommend a combination
      of isotope analysis and satellite-tracking as the best means of generating
      aggregate movement data for informing disease models.

PMID- 25045324
TI  - Jail Inmates' Perceived and Anticipated Stigma: Implications for Post-release
      Functioning.
AB  - Research shows that offenders perceive stigma, but the accuracy of these
      perceptions has not been assessed, nor their impact on successful reintegration.
      In a longitudinal study, jail inmates (N = 168) reported perceptions of stigma
      toward criminals and anticipated stigma just prior to release. A diverse college
      sample completed a parallel survey assessing stigmatizing attitudes toward
      criminals. Inmates' perceived stigma was significantly higher than students'
      stigmatizing attitudes. Perceived stigma positively predicted post-release
      employment for African-American inmates, but not for Caucasians. Anticipated
      stigma negatively predicted arrests for Caucasian inmates, but not for African
      Americans. Perceived and anticipated stigma may have different implications for
      reintegration, and these implications may vary across race.

PMID- 25045325
TI  - Learning Instance-Specific Predictive Models.
AB  - This paper introduces a Bayesian algorithm for constructing predictive models
      from data that are optimized to predict a target variable well for a particular
      instance. This algorithm learns Markov blanket models, carries out Bayesian model
      averaging over a set of models to predict a target variable of the instance at
      hand, and employs an instance-specific heuristic to locate a set of suitable
      models to average over. We call this method the instance-specific Markov blanket
      (ISMB) algorithm. The ISMB algorithm was evaluated on 21 UCI data sets using five
      different performance measures and its performance was compared to that of
      several commonly used predictive algorithms, including nave Bayes, C4.5 decision
      tree, logistic regression, neural networks, k-Nearest Neighbor, Lazy Bayesian
      Rules, and AdaBoost. Over all the data sets, the ISMB algorithm performed better
      on average on all performance measures against all the comparison algorithms.

PMID- 25045327
TI  - Edward I. Lee, MD.

PMID- 25045328
TI  - Vascular anomalies.

PMID- 25045326
TI  - Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder.
AB  - Uric acid nephrolithiasis is characteristically a manifestation of a systemic
      metabolic disorder. It has a prevalence of about 10% among all stone formers, the
      third most common type of kidney stone in the industrialized world. Uric acid
      stones form primarily due to an unduly acid urine; less deciding factors are
      hyperuricosuria and a low urine volume. The vast majority of uric acid stone
      formers have the metabolic syndrome, and not infrequently, clinical gout is
      present as well. A universal finding is a low baseline urine pH plus insufficient
      production of urinary ammonium buffer. Persons with gastrointestinal disorders,
      in particular chronic diarrhea or ostomies, and patients with malignancies with a
      large tumor mass and high cell turnover comprise a less common but nevertheless
      important subset. Pure uric acid stones are radiolucent but well visualized on
      renal ultrasound. A 24 h urine collection for stone risk analysis provides
      essential insight into the pathophysiology of stone formation and may guide
      therapy. Management includes a liberal fluid intake and dietary modification.
      Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is
      essential, as undissociated uric acid deprotonates into its much more soluble
      urate form.

PMID- 25045329
TI  - Vascular tumors.
AB  - VASCULAR ANOMALIES ARE DIVIDED INTO TWO MAIN GROUPS: tumors and malformations.
      Vascular tumors are a large and complex group of lesions, especially for
      clinicians with none or little experience in this field. In the past, these
      lesions caused a great deal of confusion because many appear analogous to the
      naked eye. Thankfully, recent advances in diagnostic techniques have helped the
      medical community to enhance our comprehension, accurately label, diagnose, and
      treat these lesions. In this article, we will review the most frequent vascular
      tumors and provide the reader with the tools to properly label, diagnose, and
      manage these complex lesions.

PMID- 25045330
TI  - Vascular malformations: a review.
AB  - Identification and treatment of vascular malformations is a challenging endeavor
      for physicians, especially given the great concern and anxiety created for
      patients and their families. The goal of this article is to provide a review of
      vascular malformations, organized by subtype, including capillary, venous,
      lymphatic and arteriovenous malformations. Only by developing a clear
      understanding of the clinical aspects, diagnostic tools, imaging modalities, and
      options for intervention will appropriate care be provided and results maximized.

PMID- 25045332
TI  - Radiographic findings associated with vascular anomalies.
AB  - Imaging of patients with vascular tumors and malformations has been sufficiently
      refined to answer pertinent questions when making treatment decisions in this
      challenging subgroup of pediatric patients. The imaging modalities at hand
      include conventional radiography, Doppler ultrasound, and magnetic resonance
      imaging with time-resolved, contrast-material enhanced magnetic resonance
      angiography. This review article will focus on the characteristic imaging
      features of some focal and diffuse vascular lesions, which have been classified
      by their clinical history and physical exam, and further labeled as a vascular
      tumor or slow-flow versus high-flow vascular malformation based on the updated
      classification system proposed by the International Society for the Study of
      Vascular Anomalies. The recent advances in knowledge regarding the biology of
      these vascular anomalies have led to increased awareness of the current
      nomenclature. Moreover, with better understanding of the imaging features, the
      radiologist has become a key player in the multidisciplinary approach offered at
      various institutions where appropriate treatment algorithms and interventional
      strategies are put together. This is crucial in avoiding misdiagnosis and
      improper management. 

PMID- 25045331
TI  - A review of vascular anomalies: genetics and common syndromes.
AB  - Vascular tumors and malformations are unique in that affected cells exhibit
      disrupted angiogenesis. The current treatment options often yield suboptimal
      results. New insight into the genetics and molecular basis of vascular anomalies
      may pave the way for potential development of targeted therapy. The authors
      review the genetic and molecular basis of vascular anomalies and common
      associated syndromes. 

PMID- 25045333
TI  - Medical therapy for pediatric vascular anomalies.
AB  - Vascular anomalies (VAs) comprise a large variety of individual diagnoses that in
      different phases of treatment require a diverse number of medical specialists to
      provide optimal care. Medical therapies include agents usually associated with
      cancer chemotherapy, such as vincristine, as well more immunomodulatory types of
      drugs, such as glucocorticoids and sirolimus. These immunomodulating drugs are
      being successfully applied in cases that are typically categorized as vascular
      tumors, including kaposiform hemangioendothelioma (KHE) and tufted angioma (TA),
      as well as some of the more invasive types of vascular malformations (i.e.,
      microcystic lymphatic malformations and blue rubber bleb nevus syndrome (BRBNS).
      These therapies need to be combined with good supportive care, which often
      involves anticoagulation, antimicrobial prophylaxis, and comprehensive pain and
      symptom-relief strategies, as well as appropriate drug monitoring and management
      of side effects of medical treatment. The optimal care of these patients
      frequently involves close collaboration between surgeons, interventional and
      conventional radiologists, medical subspecialists, and nurses. 

PMID- 25045334
TI  - Beta-blockers as therapy for infantile hemangiomas.
AB  - Infantile hemangiomas (IH) are common benign vascular tumors seen in children.
      Although the majority will improve spontaneously without treatment, a small
      subset will require therapy due to a variety of complications. Less than a decade
      ago, propranolol replaced corticosteroids as first-line treatment for most IH and
      it has proven to be a relatively safe, effective therapy. After initiation of
      propranolol, most hemangiomas show evidence of significant improvement relatively
      rapidly, often within days. Although propranolol is generally felt to have a more
      limited side-effect profile than systemic corticosteroids, its use has been
      infrequently associated with adverse events, including sleep disturbances,
      acrocyanosis, hypotension, bradycardia, respiratory events, and hypoglycemia.
      Rarely, hypoglycemic seizures have been reported, usually occurring in the
      setting of prolonged fasting. 

PMID- 25045335
TI  - Vascular malformations: approach by an interventional radiologist.
AB  - Children with vascular malformations are best managed with a multidisciplinary
      team of specialists. Interventional radiology may deliver primary treatment such
      as staged sclerotherapy and embolization for malformations that are poor
      candidates for primary surgical resection or play a supportive role such as
      preoperative or intraoperative embolization. A thorough understanding of vascular
      morphology and flow dynamics is imperative to choosing the best treatment tool
      and technique. In this review, the author discusses the selection of techniques
      and tools used to treat vascular malformations based on their angiographic
      morphology. 

PMID- 25045336
TI  - Vascular anomalies and airway concerns.
AB  - Vascular anomalies, both tumors and malformations, can occur anywhere in the
      body, including the airway, often without any external manifestations. However,
      vascular anomalies involving the airway deserve special consideration as proper
      recognition and management can be lifesaving. In this article, the authors
      discuss vascular anomalies as they pertains to the airway, focusing on proper
      diagnosis, diagnostic modalities, and therapeutic options. 

PMID- 25045338
TI  - An Angular Overlap Model for Cu(II) Ion in the AMOEBA Polarizable Force Field.
AB  - An extensible polarizable force field for transition metal ion was developed
      based on AMOEBA and the angular overlap model (AOM) with consistent treatment of
      electrostatics for all atoms. Parameters were obtained by fitting molecular
      mechanics (MM) energies to various ab initio gas-phase calculations. The results
      of parameterization were presented for copper (II) ion ligated to water and model
      fragments of amino acid residues involved in the copper binding sites of type 1
      copper proteins. Molecular dynamics (MD) simulations were performed on aqueous
      copper (II) ion at various temperatures, as well as plastocyanin (1AG6) and
      azurin (1DYZ). Results demonstrated that the AMOEBA-AOM significantly improves
      the accuracy of classical MM in a number of test cases when compared to ab initio
      calculations. The Jahn-Teller distortion for hexa-aqua copper (II) complex was
      handled automatically without specifically designating axial and in-plane
      ligands. Analyses of MD trajectories resulted in a 6-coordination first solvation
      shell for aqueous copper (II) ion and a 1.8ns average residence time of water
      molecules. The ensemble average geometries of 1AG6 and 1DYZ copper binding sites
      were in general agreement with X-ray and previous computational studies.

PMID- 25045337
TI  - High dose Anakinra for treatment of severe neonatal Kawasaki disease: a case
      report.
AB  - We report an 11-week-old female who presented with Kawasaki disease (KD)
      complicated by macrophage activation syndrome (MAS). The infant presented to the
      hospital with persistent fever, cough, diarrhea, and emesis, among other
      symptoms. Her condition quickly began to decompensate, and she developed classic
      features (conjunctivitis, rash, cracked lips, distal extremity edema) prompting a
      diagnosis of acute KD. The patient was treated with standard therapy for KD
      including three doses of intravenous immunoglobulin (IVIG), aspirin, and high
      dose glucocorticoids with no change in her condition. Due to a high suspicion for
      MAS, high dose anakinra therapy was initiated resulting in dramatic clinical
      improvements. She also received one dose of infliximab for concern for coronary
      artery changes, and over the course of several months, anakinra and high dose
      glucocorticoids were tapered. Nearly complete reversal of echocardiogram changes
      were observed after 8 months, and the infant is now off all immunosuppressive
      therapy. In this case report, we briefly review the importance of early
      recognition of MAS in pediatric patient populations with rheumatic diseases, and
      we suggest early initiation of anakinra therapy as a rapid and effective
      treatment option. 

PMID- 25045340
TI  - Effect of ZnO:Cs2CO3 on the performance of organic photovoltaics.
AB  - We demonstrate a new solution-processed electron transport layer (ETL), zinc
      oxide doped with cesium carbonate (ZnO:Cs2CO3), for achieving organic
      photovoltaics (OPVs) with good operational stability at ambient air. An OPV
      employing the ZnO:Cs2CO3 ETL exhibits a fill factor of 62%, an open circuit
      voltage of 0.90 V, and a short circuit current density of -6.14 mA/cm(2) along
      with 3.43% power conversion efficiency. The device demonstrated air stability for
      a period over 4 weeks. In addition, we also studied the device structure
      dependence on the performance of organic photovoltaics. Thus, we conclude that
      ZnO:Cs2CO3 ETL could be employed in a suitable architecture to achieve high
      performance OPV. 

PMID- 25045339
TI  - DETECTION OF LACTOBACILLI IN MONTHLY MAIL-IN STOOL SAMPLES FROM 3-18 MONTHS OLD
      INFANTS AT GENETIC RISK FOR TYPE 1 DIABETES.
AB  - The feasibility to detect lactobacilli in mail-in infant stools collected monthly
      from 3-18 months old children was investigated. The aim was to determine total
      lactobacilli and Lactobacillus plantarum (L. plantarum) content (ng/g feces) in
      50 infants each from Colorado (648 samples), Finland (624 samples) and Sweden
      (685 samples) who participated in the TEDDY (The Environmental Determinants of
      Diabetes in the Young) study. Total lactobacilli content varied markedly between
      5 and 16,800 ng/g feces in the three clinical sites within and between
      individuals especially in infants. L.plantarum also varied markedly intra- and
      inter-individually from <0.5 - 736 ng/g feces. A higher variability of total
      lactobacilli was found before 10 months of age than after in the three different
      clinical sites. Sweden had the lowest total lactobacilli content compared to
      Colorado and Finland while the L.plantarum content was higher in Sweden. Mail-in
      stool samples from infants should prove useful in analyzing probiotics in
      childhood.

PMID- 25045341
TI  - Efficiency improvement of InGaP/GaAs/Ge solar cells by hydrothermal-deposited ZnO
      nanotube structure.
AB  - In this paper, a zinc oxide (ZnO) nanotube, fabricated by the hydrothermal growth
      method on triple-junction (T-J) solar cell devices to enhance efficiency, is
      investigated. Compared to those of bare T-J solar cells (without antireflection
      (AR) coating) and solar cells with Si3N4 AR coatings, the experimental results
      show that the T-J solar cells, which use a ZnO nanotube as an AR coating, have
      the lowest reflectance in the short wavelength spectrum. The ZnO nanotube has the
      lowest light reflection among all experimental samples, especially in the range
      of 350 to 500 nm from ultraviolet (UV) to visible light. It was found that a ZnO
      nanotube can enhance the conversion efficiency by 4.9%, compared with a
      conventional T-J solar cell. The Si3N4 AR coatings also enhance the conversion
      efficiency by 3.2%.The results show that a cell with ZnO nanotube coating could
      greatly improve solar cell performances. 

PMID- 25045342
TI  - The role of Si interstitials in the migration and growth of Ge nanocrystallites
      under thermal annealing in an oxidizing ambient.
AB  - We report a unique growth and migration behavior of Ge nanocrystallites mediated
      by the presence of Si interstitials under thermal annealing at 900 degrees C
      within an H2O ambient. The Ge nanocrystallites were previously generated by the
      selective oxidation of SiGe nanopillars and appeared to be very sensitive to the
      presence of Si interstitials that come either from adjacent Si3N4 layers or from
      within the oxidized nanopillars. A cooperative mechanism is proposed, wherein the
      Si interstitials aid in both the migration and coarsening of these Ge
      nanocrystallites through Ostwald ripening, while the Ge nanocrystallites, in
      turn, appear to enhance the generation of Si interstitials through catalytic
      decomposition of the Si-bearing layers. 

PMID- 25045344
TI  - An Elegant Algorithm for the Construction of Suffix Arrays.
AB  - The suffix array is a data structure that finds numerous applications in string
      processing problems for both linguistic texts and biological data. It has been
      introduced as a memory efficient alternative for suffix trees. The suffix array
      consists of the sorted suffixes of a string. There are several linear time suffix
      array construction algorithms (SACAs) known in the literature. However, one of
      the fastest algorithms in practice has a worst case run time of O(n2). The
      problem of designing practically and theoretically efficient techniques remains
      open. In this paper we present an elegant algorithm for suffix array construction
      which takes linear time with high probability; the probability is on the space of
      all possible inputs. Our algorithm is one of the simplest of the known SACAs and
      it opens up a new dimension of suffix array construction that has not been
      explored until now. Our algorithm is easily parallelizable. We offer parallel
      implementations on various parallel models of computing. We prove a lemma on the
      l-mers of a random string which might find independent applications. We also
      present another algorithm that utilizes the above algorithm. This algorithm is
      called RadixSA and has a worst case run time of O(n log n). RadixSA introduces an
      idea that may find independent applications as a speedup technique for other
      SACAs. An empirical comparison of RadixSA with other algorithms on various
      datasets reveals that our algorithm is one of the fastest algorithms to date. The
      C++ source code is freely available at
      http://www.engr.uconn.edu/~man09004/radixSA.zip.

PMID- 25045343
TI  - Internet-Based Physical Activity Interventions.
AB  - This article provides a comprehensive review of Internet- and Website-based
      physical activity interventions targeting adult populations. Search procedures
      identified 72 unique Internet-based physical activity interventions published in
      peer-reviewed journals. Participants of the studies were predominately White,
      middle-aged (mean age = 43.3 years), and female (65.9%). Intervention durations
      ranged from 2 weeks to 13 months (median = 12 weeks). Forty-six of the studies
      were randomized controlled trials, 21 were randomized trials without a control
      condition, 2 were non-randomized controlled trials, and 3 used a single-group
      design. The majority of studies (n = 68) assessed outcomes immediately following
      the end of the intervention period, and 16 studies provided delayed
      postintervention assessments. Forty-four of the 72 studies (61.1%) reported
      significant increases in physical activity. Future directions for Internet-based
      physical activity interventions include increasing representation of minority and
      male populations in Internet-based efforts, conducting delayed postintervention
      follow-up assessments, and incorporating emerging technologies (ie, cellular and
      Smartphones) into Internet-based physical activity efforts.

PMID- 25045345
TI  - Resistance of Cancer Cells to Targeted Therapies Through the Activation of
      Compensating Signaling Loops.
AB  - The emergence of low molecular weight kinase inhibitors as "targeted" drugs has
      led to remarkable advances in the treatment of cancer patients. The clinical
      benefits of these tumor therapies, however, vary widely in patient populations
      and with duration of treatment. Intrinsic and acquired resistance against such
      drugs limits their efficacy. In addition to the well studied mechanisms of
      resistance based upon drug transport and metabolism, genetic alterations in drug
      target structures and the activation of compensatory cell signaling have received
      recent attention. Adaptive responses can be triggered which counteract the
      initial dependence of tumor cells upon a particular signaling molecule and allow
      only a transient inhibition of tumor cell growth. These compensating signaling
      mechanisms are often based upon the relief of repression of regulatory feedback
      loops. They might involve cell autonomous, intracellular events or they can be
      mediated via the secretion of growth factor receptor ligands into the tumor
      microenvironment and signal induction in an auto- or paracrine fashion. The
      transcription factors Stat3 and Stat5 mediate the biological functions of
      cytokines, interleukins and growth factors and can be considered as endpoints of
      multiple signaling pathways. In normal cells this activation is transient and the
      Stat molecules return to their non-phosphorylated state within a short time
      period. In tumor cells the balance between activating and de-activating signals
      is disturbed resulting in the persistent activation of Stat3 or Stat5. The
      constant activation of Stat3 induces the expression of target genes, which cause
      the proliferation and survival of cancer cells, as well as their migration and
      invasive behavior. Activating components of the Jak-Stat pathway have been
      recognized as potentially valuable drug targets and important principles of
      compensatory signaling circuit induction during targeted drug treatment have been
      discovered in the context of kinase inhibition studies in HNSCC cells [1]. The
      treatment of HNSCC with a specific inhibitor of c-Src, initially resulted in
      reduced Stat3 and Stat5 activation and subsequently an arrest of cell
      proliferation and increased apoptosis. However, the inhibition of c-Src only
      caused a persistent inhibition of Stat5, whereas the inhibition of Stat3 was only
      transient. The activation of Stat3 was restored within a short time period in the
      presence of the c-Src inhibitor. This process is mediated through the suppression
      of P-Stat5 activity and the decrease in the expression of the Stat5 dependent
      target gene SOCS2, a negative regulator of Jak2. Jak2 activity is enhanced upon
      SOCS2 downregulation and causes the reactivation of Stat3. A similar observation
      has been made upon inhibition of Bmx, bone marrow kinase x-linked, activated in
      the murine glioma cell lines Tu-2449 and Tu-9648. Its inhibition resulted in a
      transient decrease of P-Stat3 and the induction of a compensatory Stat3
      activation mechanism, possibly through the relief of negative feedback inhibition
      and Jak2 activation. These observations indicate that the inhibition of a single
      tyrosine kinase might not be sufficient to induce lasting therapeutic effects in
      cancer patients. Compensatory kinases and pathways might become activated and
      maintain the growth and survival of tumor cells. The definition of these escape
      pathways and their preemptive inhibition will suggest effective new combination
      therapies for cancer.

PMID- 25045346
TI  - Survival and synergistic growth of mixed cultures of bifidobacteria and
      lactobacilli combined with prebiotic oligosaccharides in a gastrointestinal tract
      simulator.
AB  - BACKGROUND: Probiotics, especially in combination with non-digestible
      oligosaccharides, may balance the gut microflora while multistrain preparations
      may express an improved functionality over single strain cultures. In vitro
      gastrointestinal models enable to test survival and growth dynamics of mixed
      strain probiotics in a controlled, replicable manner. METHODS: The robustness and
      compatibility of multistrain probiotics composed of bifidobacteria and
      lactobacilli combined with mixed prebiotics (galacto-, fructo- and xylo
      oligosaccharides or galactooligosaccharides and soluble starch) were studied
      using a dynamic gastrointestinal tract simulator (GITS). The exposure to acid and
      bile of the upper gastrointestinal tract was followed by dilution with a
      continuous decrease of the dilution rate (de-celerostat) to simulate the
      descending nutrient availability of the large intestine. The bacterial numbers
      and metabolic products were analyzed and the growth parameters determined.
      RESULTS: The most acid- and bile-resistant strains were Lactobacillus plantarum
      F44 and L. paracasei F8. Bifidobacterium breve 46 had the highest specific growth
      rate and, although sensitive to bile exposure, recovered during the dilution
      phase in most experiments. B. breve 46, L. plantarum F44, and L. paracasei F8
      were selected as the most promising strains for further studies. CONCLUSIONS: De
      celerostat cultivation can be applied to study the mixed bacterial cultures under
      defined conditions of decreasing nutrient availability to select a compatible set
      of strains.

PMID- 25045349
TI  - Synergistic effect of elastic stockings to maintain volume losses after
      mechanical lymphatic therapy.
AB  - The objective of the current study was to assess whether Venosan elastic
      stockings have a synergistic effect on the maintenance of results after
      Mechanical Lymphatic Therapy. Eleven patients with grade II lymphedema of the
      legs, regardless of cause, were evaluated in the Clinica Godoy between September
      and November 2012. The participants' ages ranged from 53 to 83 years old with a
      mean of 65.1 years. Two groups were formed with Group I using Venosan elastic
      stockings and Group II not using any type of compression therapy. Evaluations of
      the lymphedematous legs were performed before and after each drainage session
      using bioimpedance. Patients who wore elastic stockings had a greater volume
      reduction than those who did not wear stockings (unpaired t-test: P value <
      0.001). 

PMID- 25045350
TI  - Impact of environmental conditions on the survival of cryptosporidium and giardia
      on environmental surfaces.
AB  - The objective of this study was to find out the impact of environmental
      conditions on the survival of intestinal parasites on environmental surfaces
      commonly implicated in the transmission of these parasites. The study was
      performed by incubating Cryptosporidium and Giardia (oo)cysts on environmentally
      relevant surfaces such as brushed stainless steel, formica, ceramic, fabric, and
      skin. Parallel experiments were conducted using clean and soiled coupons
      incubated under three temperatures. The die-off coefficient rates (K) were
      calculated using first-order exponential formula. For both parasites, the fastest
      die-off was recorded on fabric, followed by ceramic, formica, skin, and steel.
      Die-off rates were directly correlated to the incubation temperatures and surface
      porosity. The presence of organic matter enhanced the survivability of the
      resting stages of test parasites. The decay rates calculated in this study can be
      used in models for public health decision-making process and highlights the
      mitigation role of hand hygiene agents in their prevention and control. 

PMID- 25045351
TI  - Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D
      Measurement Using the ADVIA Centaur Vitamin D Total Assay.
AB  - Vitamin D status in different populations relies on accurate measurement of total
      serum 25-hydroxyvitamin D [25(OH)D] concentrations [i.e., 25(OH)D3 and 25(OH)D2].
      This study evaluated agreement between the ADVIA Centaur Vitamin D Total assay
      for 25(OH)D testing (traceable to the NIST-Ghent reference method procedure) and
      a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for various
      populations with different levels of vitamin D binding protein (DBP). Total serum
      25(OH)D concentrations were measured for 36 pregnant women, 40 hemodialysis
      patients, and 30 samples (DBP-spiked or not) from healthy subjects. ELISA
      measured DBP levels. The mean serum DBP concentrations were higher for pregnancy
      (415 MUg/mL) and lower for hemodialysis subjects (198 MUg/mL) than for healthy
      subjects and were highest for spiked serum (545 MUg/mL). The average bias between
      the ADVIA Centaur assay and the LC-MS/MS method was -1.4% (healthy), -6.1%
      (pregnancy), and 4.4% (hemodialysis). The slightly greater bias for samples from
      some pregnancy and hemodialysis subjects with serum DBP levels outside of the
      normal healthy range fell within a clinically acceptable range-reflected by
      analysis of their low-range (<=136 MUg/mL), medium-range (137-559 MUg/mL), and
      high-range (>=560 MUg/mL) DBP groups. Thus, the ADVIA Centaur Vitamin D Total
      assay demonstrates acceptable performance compared with an LC-MS/MS method for
      populations containing different amounts of DBP. 

PMID- 25045348
TI  - Priming cancer cells for drug resistance: role of the fibroblast niche.
AB  - Conventional and targeted chemotherapies remain integral strategies to treat
      solid tumors. Despite the large number of anti-cancer drugs available,
      chemotherapy does not completely eradicate disease. Disease recurrence and the
      growth of drug resistant tumors remain significant problems in anti-cancer
      treatment. To develop more effective treatment strategies, it is important to
      understand the underlying cellular and molecular mechanisms of drug resistance.
      It is generally accepted that cancer cells do not function alone, but evolve
      through interactions with the surrounding tumor microenvironment. As key cellular
      components of the tumor microenvironment, fibroblasts regulate the growth and
      progression of many solid tumors. Emerging studies demonstrate that fibroblasts
      secrete a multitude of factors that enable cancer cells to become drug resistant.
      This review will explore how fibroblast secretion of soluble factors act on
      cancer cells to enhance cancer cell survival and cancer stem cell renewal,
      contributing to the development of drug resistant cancer.

PMID- 25045347
TI  - Effect of the amount and type of dietary fat on cardiometabolic risk factors and
      risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a
      systematic review.
AB  - The effects of both the amount and quality of dietary fat have been studied
      intensively during the past decades. Previously, low-fat diets were recommended
      without much attention to the quality of fat, whereas there is general emphasis
      on the quality of fat in current guidelines. The objective of this systematic
      review (SR) was to assess the evidence of an effect of the amount and type of
      dietary fat on body weight (BW), risk factors, and risk of non-communicable
      diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and
      cancer in healthy subjects or subjects at risk for these diseases. This work was
      performed in the process of updating the fourth edition of the Nordic Nutrition
      Recommendations from 2004. The literature search was performed in October 2010
      covering articles published since January 2000. A complementary search was done
      in February 2012 covering literature until December 2011. Two authors
      independently selected articles for inclusion from a total of about 16,000
      abstracts according to predefined criteria. Randomized controlled trials (RCT)
      and prospective cohort studies (PCS) were included as well as nested case-control
      studies. A few retrospective case-control studies were also included when limited
      or no data were available from other study types. Altogether 607 articles were
      quality graded and the observed effects in these papers were summarized.
      Convincing evidence was found that partial replacement of saturated fat (SFA)
      with polyunsaturated fat (PUFA) or monounsaturated fat (MUFA) lowers fasting
      serum/plasma total and LDL cholesterol concentrations. The evidence was probable
      for a decreasing effect of fish oil on concentration of serum/plasma total
      triglycerides as compared with MUFA. Beneficial effect of MUFA both on insulin
      sensitivity and fasting plasma/serum insulin concentration was considered as
      probable in comparisons of MUFA and carbohydrates versus SFA, whereas no effect
      was found on fasting glucose concentration in these comparisons. There was
      probable evidence for a moderate direct association between total fat intake and
      BW. Furthermore, there was convincing evidence that partial replacement of SFA
      with PUFA decreases the risk of CVD, especially in men. This finding was
      supported by an association with biomarkers of PUFA intake; the evidence of a
      beneficial effect of dietary total PUFA, n-6 PUFA, and linoleic acid (LA) on CVD
      mortality was limited suggestive. Evidence for a direct association between total
      fat intake and risk of T2DM was inconclusive, whereas there was limited
      suggestive evidence from biomarker studies that LA is inversely associated with
      the risk of T2DM. However, there was limited-suggestive evidence in biomarker
      studies that odd-chain SFA found in milk fat and fish may be inversely related to
      T2DM, but these associations have not been supported by controlled studies. The
      evidence for an association between dietary n-3 PUFA and T2DM was inconclusive.
      Evidence for effects of fat on major types of cancer was inconclusive regarding
      both the amount and quality of dietary fat, except for prostate cancer where
      there was limited-suggestive evidence for an inverse association with intake of
      ALA and for ovarian cancer for which there was limited-suggestive evidence for a
      positive association with intake of SFA. This SR reviewed a large number of
      studies focusing on several different health outcomes. The time period covered by
      the search may not have allowed obtaining the full picture of the evidence in all
      areas covered by this SR. However, several SRs and meta-analyses that covered
      studies published before year 2000 were evaluated, which adds confidence to the
      results. Many of the investigated questions remain unresolved, mainly because of
      few studies on certain outcomes, conflicting results from studies, and lack of
      high quality-controlled studies. There is thus an evident need of highly
      controlled RCT and PCS with sufficient number of subjects and long enough
      duration, specifically regarding the effects of the amount and quality of dietary
      fat on insulin sensitivity, T2DM, low-grade inflammation, and blood pressure. New
      metabolic and other potential risk markers and utilization of new methodology in
      the area of lipid metabolism may provide new insight. 

PMID- 25045352
TI  - Radiofrequency ablation compared to surgery for the treatment of benign thyroid
      nodules.
AB  - Objective. Benign thyroid nodules are a common occurrence whose only remedy, in
      case of symptoms, has always been surgery until the advent of new techniques,
      such as radiofrequency ablation (RFA). This study aimed at evaluating RFA
      efficacy, tolerability, and costs and comparing them to hemithyroidectomy for the
      treatment of benign thyroid nodules. Design and Methods. 37 patients who
      underwent RFA were retrospectively compared to 74 patients surgically treated,
      either in a standard inpatient or in a short-stay surgical regimen. Efficacy,
      tolerability, and costs were compared. The contribution of final pathology was
      also taken into account. Results. RFA reduced nodular volume by 70% after 12
      months and it was an effective method for treating nodule-related clinical
      problems, but it was not as effective as surgery for the treatment of hot
      nodules. RFA and surgery were both safe, although RFA had less complications and
      pain was rare. RFA costed ?1,661.50, surgery costed ?4,556.30, and short-stay
      surgery costed ?4,139.40 per patient. RFA, however, did not allow for any
      pathologic analysis of the nodules, which, in 6 patients who had undergone
      surgery (8%), revealed that the nodules harboured malignant cells. Conclusions.
      RFA might transform our approach to benign thyroid nodules. 

PMID- 25045353
TI  - Conservative treatment of bisphosphonate-related osteonecrosis of the jaw in
      multiple myeloma patients.
AB  - The use of intravenous bisphosphonates (pamidronate or zoledronic acid) is the
      cornerstone for the management of multiple myeloma-(MM-) related bone disease.
      However, osteonecrosis of the jaw (ONJ) is a rare, but sometimes difficult to
      manage, adverse effect of bisphosphonates therapy. A retrospective review of all
      MM patients who were treated with bisphosphonates in our department, from 2003 to
      2013, and developed ONJ was performed. According to inclusion criteria, 38
      patients were studied. All these patients were treated as conservatively as
      possible according to the American Association of Oral and Maxillofacial Surgeons
      criteria. Patients were managed with observation, oral antibacterial mouth rinse
      with chlorhexidine, oral antibiotics, pain control with analgesics, nonsurgical
      sequestrectomy with or without simultaneous administration of antibiotics, or
      major surgery with or without antibiotics. Healing of the lesions was achieved in
      23 (60%) patients who were treated with conservative measures; the median time to
      healing was 12 months (95% CI: 4-21). The number of bisphosphonates infusions
      influenced the time to healing: the median time to healing for patients who
      received <16 infusions was 7 months and for those with >16 infusions was it 14
      months (P = 0.017). We conclude that a primarily nonsurgical approach appears to
      be a successful management strategy for bisphosphonate-related ONJ. 

PMID- 25045354
TI  - How neuroscience relates to hearing aid amplification.
AB  - Hearing aids are used to improve sound audibility for people with hearing loss,
      but the ability to make use of the amplified signal, especially in the presence
      of competing noise, can vary across people. Here we review how neuroscientists,
      clinicians, and engineers are using various types of physiological information to
      improve the design and use of hearing aids. 

PMID- 25045355
TI  - Postcoital bleeding: a review on etiology, diagnosis, and management.
AB  - Postcoital bleeding refers to spotting or bleeding that occurs after intercourse
      and is not related to menstruation. The prevalence of postcoital bleeding ranges
      from 0.7 to 9.0 percent of menstruating women. There are multiple etiologies for
      this common complaint in which most are benign such as cervicitis or cervical
      polyps. However, the most serious cause of postcoital bleeding is cervical
      cancer. There are currently no recommendations from governing bodies such as the
      American College of Obstetricians and Gynecologists on evaluating and treating
      women with postcoital bleeding. The purpose of this paper is to discuss the
      common causes of postcoital bleeding, the etiologies of postcoital bleeding, and
      the likelihood that malignancy is the underlying cause. After an extensive
      literature review, we compiled a paper illustrating the key concepts a
      practitioner should know when it comes to postcoital bleeding. Finally, this
      review will conclude with treatment options for women who are found to have an
      identifiable source for their bleeding and a discussion on the natural history of
      postcoital bleeding in women who are found to have no identifiable etiology on
      evaluation. 

PMID- 25045356
TI  - Rubella Immunity among Pregnant Women in Jeddah, Western Region of Saudi Arabia.
AB  - To determine the presence of rubella immunity among pregnant women attending
      their first prenatal visit in Jeddah, Saudi Arabia, a retrospective, descriptive,
      cross-sectional, hospital-based study (prevalence study) was undertaken. A total
      of 10276 women attending prenatal clinics between January 1, 2008, and December
      31, 2011 were included. Rubella screening tests (immunoglobulins: IgG and IgM),
      rubella antibody titer levels, patient age, gravidity, parity, and the number of
      previous abortions were analyzed. No patients tested IgM positive, and 9410
      (91.6%) were immune (IgG positive); the remaining 866 (8.4%) were susceptible.
      There were no significant differences in gravidity, parity, or the number of
      previous abortions between immune and nonimmune groups. In contrast, the immunity
      rate decreased with increasing age, with a significant difference between the
      youngest age group (15-19 years) and the oldest age group (40-49 years) (P =
      0.0005; odds ratio, 2.86; 95% confidence interval, 1.7-4.7). Rubella immunity
      among pregnant women was high (91.6%) but decreased significantly with increasing
      age. A possible explanation for this is the change in the rubella vaccination
      policy in Saudi Arabia in 2002, from 1 dose to 2 doses. In addition, antibody
      levels begin to decline after vaccination and natural infection. 

PMID- 25045357
TI  - Gastrointestinal involvement in lipoid proteinosis: a ten-year follow-up of a
      brazilian female patient.
AB  - Lipoid proteinosis is a rare autosomal recessive disease characterized by the
      deposition of hyaline material in the skin and internal organs. The main clinical
      features are hoarseness and typical skin lesions. In this report we describe the
      endoscopic and radiologic findings in a Brazilian female patient presenting
      extensive gastrointestinal involvement and the evolution of the detected lesions
      in ten years of follow-up. Initial upper endoscopy and colonoscopy showed a
      similar pattern of multiple yellowish nodules throughout the esophagus, stomach,
      duodenum, and colons. Histological analysis confirmed the diagnosis of lipoid
      proteinosis. In addition, small bowel follow through demonstrated numerous well
      defined, round, small filling defects throughout the jejunum. Ten years later,
      the esophageal lesions remained the same, but none of the previous alterations
      were detected in the stomach, duodenum, and colons. In conclusion, lipoid
      proteinosis may affect all gastrointestinal organs with the same pattern of
      macroscopic and microscopic lesions. Some lesions may regress with increasing
      age. 

PMID- 25045358
TI  - Thrombocytopenia in Plasmodium vivax Malaria: How Significant?
AB  - Introduction. Thrombocytopenia is frequently noticed with P. falciparum malaria
      but is less reported and studied with P. vivax. Materials and Methods. The study
      was conducted in the Department of Medicine, SBKS MI & RC, Pipariya. We included
      patients who were diagnosed with vivax malaria. The data regarding their clinical
      and hematological profile was collected and analysed. Result. A total of 66
      patients were included. 42 (63%) had platelet count <100000/mm(3). Mean platelet
      count was 1,18,650, range being 8000/mm(3)-6,10,000/mm(3). Amongst those with
      thrombocytopenia, 16 (38.09%) had anemia, 14 (33.33%) had serum creatinine >1.2
      gm/dL, 15 (35.71%) had jaundice (s. bilirubin > 1.2), 2 (4.76%) had altered
      sensorium, 6 (14.28%) had ARDS, 2 needed ventilator support, and 1 expired.
      Amongst those with normal platelet count, 5 (20.83%) had anemia and 1 had
      jaundice whereas none had elevated s. creatinine, altered sensorium, or lung
      involvement. Conclusion. Thrombocytopenia is now being seen more commonly with
      vivax malaria. Patients with platelet count <1 lac/cumm have more severe disease.

PMID- 25045359
TI  - Magnitude and Reasons for Harmful Traditional Practices among Children Less Than
      5 Years of Age in Axum Town, North Ethiopia, 2013.
AB  - Background. In addition to beneficial traditional practices, there are around 140
      harmful traditional practices affecting mothers and children in almost all ethnic
      groups of Ethiopia. Therefore this study might give a clue about their practice
      and associated factors. The objective of this study was to assess magnitude of
      harmful traditional practices among children less than 5 years of age in Axum
      Town, North Ethiopia. Methods. Community based cross-sectional study was
      conducted on 752 participants who were selected using multistage sampling. Simple
      random sampling method was used to select ketenas from all kebelles of Axum Town.
      After proportional allocation of sample size to eachketena, systematic random
      sampling method was used to get the study participants. Data was collected using
      interviewer administered questionnaire; it was entered and analyzed using SPSS
      version 16 and descriptive statistics was calculated. Results. Majority of the
      respondents (81.2%) were Orthodox, 78.2% of the mothers had no work, and majority
      of mothers had no formal education. Among the harmful traditional practices
      performed on children, uvula cutting alone was performed on 72.8% of children
      followed by milk teeth extraction and uvula cutting with eyebrow incision.
      Conclusion. The leading harmful traditional practice performed on children in
      this study was uvula cutting. 

PMID- 25045360
TI  - A model for the determination of pollen count using google search queries for
      patients suffering from allergic rhinitis.
AB  - Background. The transregional increase in pollen-associated allergies and their
      diversity have been scientifically proven. However, patchy pollen count
      measurement in many regions is a worldwide problem with few exceptions. Methods.
      This paper used data gathered from pollen count stations in Germany, Google
      queries using relevant allergological/biological keywords, and patient data from
      three German study centres collected in a prospective, double-blind, randomised,
      placebo-controlled, multicentre immunotherapy study to analyse a possible
      correlation between these data pools. Results. Overall, correlations between the
      patient-based, combined symptom medication score and Google data were stronger
      than those with the regionally measured pollen count data. The correlation of the
      Google data was especially strong in the groups of severe allergy sufferers. The
      results of the three-centre analyses show moderate to strong correlations with
      the Google keywords (up to >0.8 cross-correlation coefficient, P < 0.001) in 10
      out of 11 groups (three averaged patient cohorts and eight subgroups of severe
      allergy sufferers: high IgE class, high combined symptom medication score, and
      asthma). Conclusion. For countries with a good Internet infrastructure but no
      dense network of pollen traps, this could represent an alternative for
      determining pollen levels and, forecasting the pollen count for the next day. 

PMID- 25045361
TI  - Determinants of sensitization to allergen in infants and young children.
AB  - Atopic sensitization is a complex phenomenon that changes dynamically with age
      throughout childhood; its prevalence increases with age in young children.
      Additionally, with increasing age, the prevalence of sensitization to inhalant
      allergens and the prevalence of polysensitization to allergens increase. It is
      also well established that the development of atopic sensitization is the result
      of a complex interplay of genetic and environmental factors. However, there is
      considerable heterogeneity in the literature in terms of the effect of different
      environmental exposures in young children on the subsequent risk of atopic
      sensitization and allergic diseases. Previous studies on the relationship, in
      early life, between pet ownership, sex, exposure to secondhand smoke, exposure to
      traffic-related air pollution components, and atopic sensitization have yielded
      different results. Recent studies have highlighted the importance of gene
      environment interactions, especially during early childhood, on the risk of
      subsequent atopic sensitization and allergic diseases. Therefore, pediatricians
      should consider the genetic and environmental determinants of atopic
      sensitization in infants and young children when diagnosing and treating patients
      with allergic diseases. Determining ways in which early exposure to these risk
      factors in young children may be reduced could be beneficial in preventing the
      likelihood of developing atopic sensitization. 

PMID- 25045362
TI  - Association of wheezing phenotypes with fractional exhaled nitric oxide in
      children.
AB  - Asthma comprises a heterogeneous group of disorders characterized by airway
      inflammation, airway obstruction, and airway hyperresponsiveness (AHR). Airway
      inflammation, which induces AHR and recurrence of asthma, is the main
      pathophysiology of asthma. The fractional exhaled nitric oxide (FeNO) level is a
      noninvasive, reproducible measurement of eosinophilic airway inflammation that is
      easy to perform in young children. As airway inflammation precedes asthma attacks
      and airway obstruction, elevated FeNO levels may be useful as predictive markers
      for risk of recurrence of asthma. This review discusses FeNO measurements among
      early-childhood wheezing phenotypes that have been identified in large-scale
      longitudinal studies. These wheezing phenotypes are classified into three to six
      categories based on the onset and persistence of wheezing from birth to later
      childhood. Each phenotype has characteristic findings for atopic sensitization,
      lung function, AHR, or FeNO. For example, in one birth cohort study, children
      with asthma and persistent wheezing at 7 years had higher FeNO levels at 4 years
      compared to children without wheezing, which suggested that FeNO could be a
      predictive marker for later development of asthma. Preschool-aged children with
      recurrent wheezing and stringent asthma predictive indices also had higher FeNO
      levels in the first 4 years of life compared to children with wheezing and loose
      indices or children with no wheeze, suggesting that FeNO measurements may provide
      an additional parameter for predicting persistent wheezing in preschool children.
      Additional large-scale longitudinal studies are required to establish cutoff
      levels for FeNO as a risk factor for persistent asthma. 

PMID- 25045363
TI  - Cardiovascular risk factors of early atherosclerosis in school-aged children
      after Kawasaki disease.
AB  - PURPOSE: The aim of this study was to determine whether school-aged children with
      Kawasaki disease (KD) have an increased risk for early atherosclerosis. METHODS:
      The study included 98 children. The children were divided into the following
      groups: group A (n=19), KD with coronary arterial lesions that persisted or
      regressed; group B (n=49), KD without coronary arterial lesions; and group C
      (n=30), healthy children. Anthropometric variables and the levels of biochemical
      markers, including total cholesterol, high-density lipoprotein cholesterol (HDL
      C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A, apolipoprotein
      B, homocysteine, high-sensitivity C-reactive protein (hs-CRP), and brachial
      artery stiffness using pulse wave velocity were compared among the three groups.
      RESULTS: There were no significant differences in blood pressure and body index
      among the three groups. Additionally, there was no sex-specific difference.
      Moreover, the levels of triglyceride, HDL-C, apolipoprotein A, and hs-CRP did not
      differ among the three groups. However, the levels of total cholesterol
      (P=0.018), LDL-C (P=0.0003), and apolipoprotein B (P=0.029) were significantly
      higher in group A than in group C. Further, the level of homocysteine and the
      aortic pulse wave velocity were significantly higher in groups A and B than in
      group C (P=0.0001). CONCLUSION: School-aged children after KD have high lipid
      profiles and arterial stiffness indicating an increased risk for early
      atherosclerosis.

PMID- 25045364
TI  - Outcome of inflammatory response after normothermia during cardiopulmonary bypass
      surgery in infants with isolated ventricular septal defect.
AB  - PURPOSE: A recent study analyzing several cytokines reported that long
      cardiopulmonary bypass (CPB) time and long aortic cross clamp (ACC) time were
      accompanied by enhanced postoperative inflammation, which contrasted with the
      modest influence of the degree of hypothermia. In this present study, we aimed to
      examine the effect of CPB temperature on the clinical outcome in infants
      undergoing repair of isolated ventricular septal defect (VSD). METHODS: Of the
      212 infants with isolated VSD who underwent open heart surgery (OHS) between
      January 2001 and December 2010, 43 infants were enrolled. They were classified
      into 2 groups: group 1, infants undergoing hypothermic CPB (26C-28C; n=19) and
      group 2, infants undergoing near-normothermic CPB (34C-36C; n=24). RESULTS: The
      age at the time of the OHS, and number of infants aged<3 months showed no
      significant differences between the groups. The CPB time and ACC time in group 1
      were longer than those in group 2 (88 minutes vs. 59 minutes, P=0.002, and 54
      minutes vs. 37 minutes, P=0.006 respectively). The duration of postoperative
      mechanical ventilation was 1.6 days in group 1 and 1.8 days in group 2. None of
      the infants showed postoperative neurological and developmental abnormalities.
      Moreover, no postoperative differences in the white blood cell count and C
      reactive protein levels were noted between two groups. CONCLUSION: This study
      revealed that hypothermic and near-normothermic CPB were associated with similar
      clinical outcomes and inflammatory reactions in neonates and infants treated for
      simple congenital heart disease.

PMID- 25045365
TI  - Kikuchi-Fujimoto disease mimicking malignant lymphoma with 2-[(18)F]fluoro-2
      deoxy-D-glucose PET/CT in children.
AB  - PURPOSE: Kikuchi-Fujimoto disease (KFD) is a benign disease, which is
      characterized by a cervical lymphadenopathy with fever, and it often mimics
      malignant lymphoma (ML). 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission
      tomography/computed tomography ((18)F-FDG PET/CT) is a powerful imaging modality
      for the diagnosis, staging and monitoring of ML, with the limitations including
      the nonspecific FDG uptake in infectious or inflammatory processes. This study
      compared clinical manifestations and PET/CT findings between KFD and ML patients.
      METHODS: We retrospectively reviewed the medical records of 23 patients with KFD
      and 33 patients with ML, diagnosed histopathologically, between January 2000 and
      May 2013 at the Department of Pediatrics, Yeungnam University Medical Center.
      Among them, we analyzed the clinical manifestations, laboratory findings and
      characteristics, and the amount of (18)F-FDG uptake between 8 KFD and 9 ML
      patients who had (18)F-FDG PET/CT. RESULTS: The (18)F-FDG PET/CT maximum
      standardized uptake values (SUVmax) ranged from 8.3 to 22.5 (mean, 12.0) in KFDs,
      and from 5.8 to 34.3 (mean, 15.9) in MLs. There were no significant differences
      in SUVmax between KFDs and MLs. (18)F-FDG PET/CT with ML patients showed hot
      uptakes in the extranodal organs, such as bone marrow, small bowel, thymus,
      kidney, orbit and pleura. However, none of the KFD cases showed extranodal uptake
      (P<0.001). (18)F-FDG PET/CT findings of KFD with nodal involvement only were
      indistinguishable from those of ML. CONCLUSION: Patients who had extranodal
      involvement on PET/CT were more likely to have malignancy than KFD.

PMID- 25045366
TI  - Myocardial atrophy in children with mitochondrial disease and Duchenne muscular
      dystrophy.
AB  - PURPOSE: Mitochondrial disease (MD) and Duchenne muscular dystrophy (DMD) are
      often associated with cardiomyopathy, but the myocardial variability has not been
      isolated to a specific characteristic. We evaluated the left ventricular (LV)
      mass by echocardiography to identify the general distribution and functional
      changes of the myocardium in patients with MD or DMD. METHODS: We retrospectively
      evaluated the echocardiographic data of 90 children with MD and 42 with DMD.
      Using two-dimensional echocardiography, including time-motion (M) mode and
      Doppler measurements, we estimated the LV mass, ratio of early to late mitral
      filling velocities (E/A), ratio of early mitral filling velocity to early
      diastolic mitral annular velocity (E/Ea), stroke volume, and cardiac output. A "z
      score" was generated using the lambda-mu-sigma method to standardize the LV mass
      with respect to body size. RESULTS: The LV mass-for-height z scores were
      significantly below normal in children with MD (-1.02+/-1.52, P<0.001) or DMD (
      0.82+/-1.61, P=0.002), as were the LV mass-for-lean body-mass z scores. The body
      mass index (BMI)-for-age z scores were far below normal and were directly
      proportional to the LV mass-for-height z scores in both patients with MD
      (R=0.377, P<0.001) and those with DMD (R=0.330, P=0.033). The LV mass-for-height
      z score correlated positively with the stroke volume index (R=0.462, P<0.001) and
      cardiac index (R=0.358, P<0.001). CONCLUSION: LV myocardial atrophy is present in
      patients with MD and those with DMD and may be closely associated with low BMI.
      The insufficient LV mass for body size might indicate deterioration of systolic
      function in these patients.

PMID- 25045367
TI  - Identification of a novel mutation in a patient with pseudohypoparathyroidism
      type Ia.
AB  - Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by
      multiform hormonal resistance including parathyroid hormone (PTH) resistance and
      Albright hereditary osteodystrophy (AHO). It is caused by heterozygous
      inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy
      presented with clinical and laboratory abnormalities including hypocalcemia,
      hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face,
      short stature, obesity, brachydactyly and osteoma cutis) which were typical of
      PHP Ia. He had a history of repeated convulsive episodes that started from the
      age of 2 months. A cranial computed tomography scan showed bilateral
      calcifications in the basal ganglia and his intelligence quotient testing
      indicated mild mental retardation. Family history revealed that the patient's
      maternal relatives, including his grandmother and 2 of his mother's siblings, had
      features suggestive of AHO. Sequencing of the GNAS gene of the patient identified
      a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion
      results in an amino acid substitution from Gln to stop codon at codon 213
      (p.Gln213(*)). To our knowledge, this is a novel mutation in GNAS. 

PMID- 25045368
TI  - Gastrointestinal hemangioma in childhood: a rare cause of gastrointestinal
      bleeding.
AB  - Gastrointestinal (GI) hemangiomas are relatively rare benign vascular tumors. The
      choice of an appropriate diagnostic method depends on patient age, anatomic
      location, and presenting symptoms. However, GI hemangiomas are not a common
      suspected cause of GI bleeding in children because of their rarity. Based on
      medical history, laboratory results, and imaging study findings, the patient
      could be treated with either medication or surgery. Herein, we report 3 cases of
      GI hemangioma found in the small bowel, rectum, and GI tract (multiple
      hemangiomas). Better knowledge and understanding of GI hemangioma could help
      reduce the delayed diagnosis rate and prevent inappropriate management. Although
      rare, GI hemangiomas should be considered in the differential diagnosis of GI
      bleeding. 

PMID- 25045370
TI  - Dual antiplatelet therapy after noncardioembolic ischemic stroke or transient
      ischemic attack: pros and cons.
AB  - Dual antiplatelet therapy simultaneously blocks different platelet activation
      pathways and might thus be more potent at inhibiting platelet activation and more
      effective at reducing major ischemic vascular events compared to antiplatelet
      monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy
      for patients with acute coronary syndrome and for those undergoing percutaneous
      coronary intervention. However, dual antiplatelet therapy carries an increased
      risk of bleeding. Patients with ischemic stroke or transient ischemic attack
      (TIA) are generally older and likely to have a fragile cerebrovascular bed, which
      further increases the risk of systemic major bleeding events and intracranial
      hemorrhage. Clinical trials and meta-analyses suggest that in comparison to
      antiplatelet monotherapy, dual antiplatelet therapy initiated early after
      noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent
      stroke and major vascular events without significantly increasing the rate of
      major bleeding events. In contrast, studies of long-term therapy in patients with
      noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding
      the benefit of dual antiplatelet therapy over monotherapy. However, the harm
      associated with major bleeding events, including intracranial hemorrhage, which
      is generally more disabling and more fatal than ischemic stroke, is likely to
      increase with dual antiplatelet therapy. Physicians should carefully assess the
      benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy
      when managing patients with ischemic stroke or TIA. 

PMID- 25045369
TI  - Depression and anxiety in people with epilepsy.
AB  - Many recent epidemiological studies have found the prevalence of depression and
      anxiety to be higher in people with epilepsy (PWE) than in people without
      epilepsy. Furthermore, people with depression or anxiety have been more likely to
      suffer from epilepsy than those without depression or anxiety. Almost one-third
      of PWE suffer from depression and anxiety, which is similar to the prevalence of
      drug-refractory epilepsy. Various brain areas, including the frontal, temporal,
      and limbic regions, are associated with the biological pathogenesis of depression
      in PWE. It has been suggested that structural abnormalities, monoamine pathways,
      cerebral glucose metabolism, the hypothalamic-pituitary-adrenal axis, and
      interleukin-1b are associated with the pathogenesis of depression in PWE. The
      amygdala and the hippocampus are important anatomical structures related to
      anxiety, and gamma-aminobutyric acid and serotonin are associated with its
      pathogenesis. Depression and anxiety may lead to suicidal ideation or attempts
      and feelings of stigmatization. These experiences are also likely to increase the
      adverse effects associated with antiepileptic drugs and have been related to poor
      responses to pharmacological and surgical treatments. Ultimately, the quality of
      life is likely to be worse in PWE with depression and anxiety than in PWE without
      these disorders, which makes the early detection and appropriate management of
      depression and anxiety in PWE indispensable. Simple screening instruments may be
      helpful for in this regard, particularly in busy epilepsy clinics. Although both
      medical and psychobehavioral therapies may ameliorate these conditions,
      randomized controlled trials are needed to confirm that. 

PMID- 25045371
TI  - T2 relaxometry using 3.0-tesla magnetic resonance imaging of the brain in early-
      and late-onset restless legs syndrome.
AB  - BACKGROUND AND PURPOSE: Previous T2 relaxometry studies have provided evidence
      for regional brain iron deficiency in patients with restless legs syndrome (RLS).
      Measurement of the iron content in several brain regions, and in particular the
      substantia nigra (SN), in early- and late-onset RLS patients using T2 relaxometry
      have yielded inconsistent results. In this study the regional iron content was
      assessed in patients with early- and late-onset RLS using magnetic resonance
      imaging (MRI), and compared the results with those in controls. METHODS: Thirty
      seven patients with idiopathic RLS (20 with early onset and 17 with late onset)
      and 40 control subjects were studied using a 3.0-tesla MRI with a gradient-echo
      sampling of free induction decay and echo pulse sequence. The regions of interest
      in the brain were measured independently by two trained analysts using software
      known as medical image processing, analysis, and visualization. The results were
      compared and a correlation analysis was conducted to investigate which brain
      areas were related to RLS clinical variables. RESULTS: The iron index in the SN
      was significantly lower in patients with late-onset RLS than in controls
      (p=0.034), while in patients with early-onset RLS there was no significant
      difference. There was no significant correlation between the SN iron index of the
      late-onset RLS group and clinical variables such as disease severity.
      CONCLUSIONS: Late-onset RLS is associated with decreased iron content in the SN.
      This finding supports the hypothesis that regional brain iron deficiency plays a
      role in the pathophysiology of late-onset RLS.

PMID- 25045372
TI  - Sleep problems associated with behavioral and psychological symptoms as well as
      cognitive functions in Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: It has been shown that sleep problems in Alzheimer's
      disease (AD) are associated with cognitive impairment and behavioral problems. In
      fact, most of studies have founded that daytime sleepiness is significantly
      correlated with cognitive decline in AD. However, a few studies have also shown
      that nighttime sleep problems are associated with cognitive function and
      behavioral symptoms in AD. Accordingly, the aim of this study was to evaluate the
      effects of nighttime sleep on cognition and behavioral and psychological symptoms
      of dementia (BPSD) in AD. METHODS: The study population comprised 117 subjects:
      63 AD patients and 54 age- and sex-matched non-demented elderly subjects.
      Detailed cognitive functions and behavioral symptoms were measured using the
      Seoul Neuropsychological Screening Battery (SNSB) and the Korean version of the
      Neuropsychiatric Inventory (NPI-K). Sleep characteristics were evaluated using
      the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K). The
      correlations between PSQI-K and SNSB scores and between PSQI-K and NPI-K scores
      were analyzed. RESULTS: In AD patients, sleep latency was found to be negatively
      correlated with praxis (p=0.041), Rey-Osterrieth Complex Figure Test (RCFT)
      immediate recall (p=0.041), and RCFT recognition (p=0.008) after controlling for
      age and education, while sleep duration and sleep efficiency were positively
      correlated with praxis (p=0.034 and p=0.025, respectively). Although no
      significant correlation was found between PSQI-K and NPI-K scores, sleep
      disturbance and total PSQI-K scores were found to be significantly associated
      with apathy/indifference in AD. CONCLUSIONS: Sleep problems such as prolonged
      sleep duration, sleep latency, and poor sleep efficiency in AD patients were
      correlated with cognitive dysfunction, and especially frontal executive and
      visuospatial functions, and BPSD. These findings suggest that treatment of
      nighttime sleep problems might improve cognition and behavioral symptoms in AD
      patients.

PMID- 25045373
TI  - Validation of a Korean version of the insomnia severity index.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to standardize and
      validate a Korean version of the Insomnia Severity Index (ISI-K), and to evaluate
      its clinical usefulness. METHODS: We translated the ISI into Korean and then
      translated it back into English to check its accuracy. The 614 patients with
      sleep disorders who were enrolled in this study comprised 169 with primary
      insomnia, 133 with comorbid insomnia, and 312 with obstructive sleep apnea. All
      subjects underwent one night of polysomnography (PSG) and completed the Korean
      versions of both the Pittsburgh Sleep Quality Index (PSQI-K) and the Epworth
      Sleepiness Scale, as well as the ISI-K. The ISI-K was compared to these sleep
      scales and various PSG sleep parameters. RESULTS: The internal consistency the
      ISI-K total score was confirmed by a Cronbach's alpha of 0.92, and the item-to
      total-score correlations (item-total correlations) ranged from 0.65 to 0.84,
      suggesting adequate reliability. The correlation between the ISI-K total score
      and PSQI-K was 0.84, which suggested adequate convergent validity. Low-to
      moderate correlations were obtained between the ISI-K total score and PSG-defined
      sleep parameters: 0.22 for sleep onset latency, 0.38 for wake after sleep onset,
      and 0.46 for sleep efficiency. A cutoff score of 15.5 on the ISI-K was optimal
      for discriminating patients with insomnia. The test-retest scores over a 4-week
      interval with 34 subjects yielded a correlation coefficient of 0.86, suggesting
      excellent temporal stability. CONCLUSIONS: The findings of this study show that
      the ISI-K is a reliable and valid instrument for assessing the severity of
      insomnia in a Korean population.

PMID- 25045374
TI  - Emergency medical care of multiple sclerosis patients: primary data from the
      mount sinai resource utilization in multiple sclerosis project.
AB  - BACKGROUND AND PURPOSE: There has been no systematic analysis of emergency
      department (ED) utilization in the multiple sclerosis (MS) population. We
      investigated the acute-care needs of MS patients using ED as a route for entry
      into healthcare services. METHODS: ED visits made by MS patients were identified.
      Data extracted included demographics, medical/neurological history, and
      workup/management in the ED. RESULTS: The Mount Sinai ED received 569 visits from
      224 MS patients during a 3-year period, of whom 33.5% were covered by Medicaid
      and 12.9% were uninsured. Patients with an Expanded Disability Status Scale score
      of >=6 accounted for 54%, 50.5% of relapsing remitting MS patients were being
      treated with disease-modifying therapies, and 74.5% of the ED visits were non
      neurological. Patients with mild-to-moderate MS were more likely to present to
      the ED for issues directly related to MS such as acute exacerbations, while those
      with severe MS presented more often due to medical issues indirectly related to
      MS, such as urinary tract infections (p<0.0001). CONCLUSIONS: Most MS patients
      seeking ED care suffer from acute non-neurological problems. The MS patients
      presenting to the ED tended to be underinsured, had high levels of disability,
      and were undertreated with disease-modifying therapies. The acute-care needs of
      MS patients evolve over the disease course, as do the resources that must be
      utilized in providing emergency care across the spectrum of MS severity.
      Understanding the characteristics, problems, and needs of MS patients utilizing
      the ED is an important step in improving care in this population from both
      clinical and public health perspectives.

PMID- 25045375
TI  - Distribution of cerebral microbleeds determines their association with impaired
      kidney function.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are associated with various
      pathologies of the cerebral small vessels according to their distribution (i.e.,
      cerebral amyloid angiopathy or hypertensive angiopathy). We investigated the
      association between CMB location and kidney function in acute ischemic stroke
      patients. METHODS: We enrolled 1669 consecutive patients with acute ischemic
      stroke who underwent gradient-recalled echo brain magnetic resonance imaging.
      Kidney function was determined using the estimated glomerular filtration rate
      (eGFR). CMBs were classified into strictly lobar, strictly nonlobar (i.e., only
      deep or infratentorial), and a combination of both lobar and nonlobar.
      Multinomial logistic regression analyses were used to determine the factors
      associated with the existence of CMBs according to their location. RESULTS: The
      patients were aged 66+/-12 years (mean+/-standard deviation), and 61.9%
      (1033/1669) of them were male. CMBs were found in 27.0% (452/1669) of the
      patients. The stroke subtypes of small-artery occlusion and cardioembolism
      occurred more frequently in those with strictly nonlobar CMBs (10.8%) and
      strictly lobar CMBs (48.8%), respectively. The mean eGFR was lower in the
      strictly nonlobar CMBs group (72+/-28 mL/min/1.73 m(2)) and the both lobar and
      nonlobar CMBs group (72+/-25 mL/min/1.73 m(2)) than in the no-CMBs group (86+/-29
      mL/min/1.73 m(2)). Multivariate multinomial logistic regression revealed that
      eGFR <60 mL/min/1.73 m(2) was independently related to strictly nonlobar CMBs
      (odds ratio=2.63, p=0.001). CONCLUSIONS: Impaired kidney function is associated
      with strictly nonlobar CMBs. Our findings indicate that the distribution of CMBs
      should be considered when evaluating their relationships or prognoses.

PMID- 25045376
TI  - Abnormal brain activity changes in patients with migraine: a short-term
      longitudinal study.
AB  - BACKGROUND AND PURPOSE: Whether or not migraine can cause cumulative brain
      alterations due to frequent migraine-related nociceptive input in patients is
      largely unclear. The aim of this study was to characterize longitudinal changes
      in brain activity between repeated observations within a short time interval in a
      group of female migraine patients, using resting-state functional magnetic
      resonance imaging. METHODS: Nineteen patients and 20 healthy controls (HC)
      participated in the study. Regional homogeneity (ReHo) and functional
      interregional connectivity were assessed to determine the focal and global
      features of brain dysfunction in migraine. The relationship between changes in
      headache parameters and longitudinal brain alterations were also investigated.
      RESULTS: All patients reported that their headache activity increased over time.
      Abnormal ReHo changes in the patient group relative to the HC were found in the
      putamen, orbitofrontal cortex, secondary somatosensory cortex, brainstem, and
      thalamus. Moreover, these brain regions exhibited longitudinal ReHo changes at
      the 6-week follow-up examination. These headache activity changes were
      accompanied by disproportionately dysfunctional connectivity in the putamen in
      the migraine patients, as revealed by functional connectivity analysis,
      suggesting that the putamen plays an important role in integrating diverse
      information among other migraine-related brain regions. CONCLUSIONS: The results
      obtained in this study suggest that progressive brain aberrations in migraine
      progress as a result of increased headache attacks.

PMID- 25045377
TI  - Chronic daily headache in Korea: prevalence, clinical characteristics, medical
      consultation and management.
AB  - BACKGROUND AND PURPOSE: Chronic daily headache (CDH) is a commonly reported
      reason for visiting hospital neurology departments, but its prevalence, clinical
      characteristics, and management have not been well documented in Korea. The
      objective of this study was to characterize the 1-year prevalence, clinical
      characteristics, medical consultations, and treatment for CDH in Korea. METHODS:
      The Korean Headache Survey (KHS) is a nationwide descriptive survey of 1507
      Korean adults aged between 19 and 69 years. The KHS investigated headache
      characteristics, sociodemographics, and headache-related disability using a
      structured interview. We used the KHS data for this study. RESULTS: The 1-year
      prevalence of CDH was 1.8% (95% confidence interval, 1.1-2.5%), and 25.7% of the
      subjects with CDH met the criteria for medication overuse. Two-thirds (66.7%) of
      CDH subjects were classified as having chronic migraine, and approximately half
      of the CDH subjects (48.1%) reported that their headaches either substantially or
      severely affected their quality of life. Less than half (40.7%) of the subjects
      with CDH reported having consulted a doctor for their headaches and 40.7% had not
      received treatment for their headaches during the previous year. CONCLUSIONS: The
      prevalence of CDH was 1.8% and medication overuse was associated with one-quarter
      of CDH cases in Korea. Many subjects with CDH do not seek medical consultation
      and do not receive appropriate treatment for their headaches.

PMID- 25045378
TI  - Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or
      Familial Parkinson's Disease.
AB  - BACKGROUND AND PURPOSE: There is some controversy regarding heterozygous
      mutations of the gene encoding parkin (PARK2) as risk factors for Parkinson's
      disease (PD), and all previous studies have been performed in non-Asian
      populations. Dosage mutation of PARK2, rather than a point mutation or small
      insertion/deletion mutation, was reported to be a risk factor for familial PD;
      dosage mutation of PARK2 is common in Asian populations. METHODS: We performed a
      gene-dosage analysis of PARK2 using real-time polymerase chain reaction for 189
      patients with early-onset PD or familial PD, and 191 control individuals. In the
      case of PD patients with heterozygous gene-dosage mutation, we performed a
      sequencing analysis to exclude compound heterozygous mutations. The association
      between heterozygous mutation of PARK2 and PD was tested. RESULTS: We identified
      22 PD patients with PARK2 mutations (11.6%). Five patients (2.6%) had compound
      heterozygous mutations, and 13 patients (6.9%) had a heterozygous mutation. The
      phase could not be determined in one patient. Three small sequence variations
      were found in 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90%
      of all of the mutations found. The frequency of a heterozygous PARK2 gene-dosage
      mutation was higher in PD patients than in the controls. CONCLUSIONS:
      Heterozygous gene-dosage mutation of PARK2 is a genetic risk factor for patients
      with early-onset or familial PD in Koreans.

PMID- 25045379
TI  - Diffusion tensor tractography analysis of the corpus callosum fibers in
      amyotrophic lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: Involvement of the corpus callosum (CC) is reported to be
      a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC
      pathology using diffusion tensor tractography analysis to identify precisely
      which fiber bundles are involved in ALS. METHODS: Diffusion tensor imaging was
      performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole
      brain tractography was performed using the multiple-region of interest (ROI)
      approach, and CC fiber bundles were extracted in two ways based on functional and
      structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs),
      and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer
      software, respectively. RESULTS: The mean fractional anisotropy (FA) values of
      the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6),
      and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS
      patients than in controls, whereas those of the primary sensory cortex (BA1, BA2,
      BA3), Broca's area (BA44/45), and the orbitofrontal cortex (BA11/47) did not
      differ significantly between the two groups. The FreeSurfer ROI approach revealed
      a very similar pattern of abnormalities. In addition, a significant correlation
      was found between the mean FA value of the CC fibers interconnecting the primary
      motor area and disease severity, as assessed using the revised Amyotrophic
      Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor
      neuron signs. CONCLUSIONS: Our findings suggest that there is some degree of
      selectivity or a gradient in the CC pathology in ALS. The CC fibers
      interconnecting the primary motor and dorsolateral prefrontal cortices may be
      preferentially involved in ALS.

PMID- 25045381
TI  - Anti-ma2 paraneoplastic encephalitis in association with recurrent cervical
      cancer.
AB  - BACKGROUND: Paraneoplastic neurological syndromes are rare, and although they are
      frequently associated with gynecological malignancies, cervical cancer is a rare
      cause. The symptoms of anti-Ma2 encephalitis are diverse and often present prior
      to the diagnosis of malignancy. CASE REPORT: We report a case of a 37-year-old
      woman with a history of cervical cancer presenting with unexplained weight gain
      and vertical supranuclear gaze palsy. Magnetic resonance imaging of the brain
      revealed lesions within the bilateral hypothalami and midbrain. Anti-Ma2
      antibodies were eventually found in the serum, prompting a search for malignancy.
      Recurrent metastatic cervical cancer was found in the retroperitoneal lymph
      nodes. CONCLUSIONS: This is the first report of cervical cancer in association
      with anti-Ma2 encephalitis, and highlights the need for a high degree of
      suspicion in patients with a cancer history presenting with neurological
      symptoms. The symptoms associated with anti-Ma2 encephalitis are diverse and
      typically precede the diagnosis of cancer in patients, and should trigger a
      search for an underlying malignancy.

PMID- 25045380
TI  - Mutation analysis of SPAST, ATL1, and REEP1 in Korean Patients with Hereditary
      Spastic Paraplegia.
AB  - BACKGROUND AND PURPOSE: Hereditary spastic paraplegia (HSP) is a genetically
      heterogeneous group of neurodegenerative disorders that are characterized by
      progressive spasticity and weakness of the lower limbs. Mutations in the spastin
      gene (SPAST) are the most common causes of HSP, accounting for 40-67% of
      autosomal dominant HSP (AD-HSP) and 12-18% of sporadic cases. Mutations in the
      atlastin-1 gene (ATL1) and receptor expression-enhancing protein 1 gene (REEP1)
      are the second and third most common causes of AD-HSP, respectively. METHODS:
      Direct sequence analysis was used to screen mutations in SPAST, ATL1, and REEP1
      in 27 unrelated Korean patients with pure and complicated HSP. Multiplex ligation
      dependent probe amplification was also performed to detect copy-number variations
      of the three genes. RESULTS: Ten different SPAST mutations were identified in 11
      probands, of which the following 6 were novel: c.760A>T, c.131C>A,
      c.1351_1353delAGA, c.376_377dupTA, c.1114A>G, and c.1372A>C. Most patients with
      SPAST mutations had AD-HSP (10/11, 91%), and the frequency of SPAST mutations
      accounted for 66.7% (10/15) of the AD-HSP patients. No significant correlation
      was found between the presence of the SPAST mutation and any of the various
      clinical parameters of pure HSP. No ATL1 and REEP1 mutations were detected.
      CONCLUSIONS: We conclude that SPAST mutations are responsible for most Korean
      cases of genetically confirmed AD-HSP. Our observation of the absence of ATL1 and
      REEP1 mutations needs to be confirmed in larger series.

PMID- 25045382
TI  - Role of high-resolution magnetic resonance imaging in the diagnosis of primary
      angiitis of the central nervous system.
AB  - BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare
      disorder and is often difficult to diagnose due to the lack of a confirmatory
      test. PACNS can generally be diagnosed based on typical angiographic findings. We
      describe herein a patient diagnosed with PACNS despite the presence of normal
      findings on conventional angiography. CASE REPORT: A 44-year-old man with a
      recent history of ischemic stroke in the right posterior cerebral artery
      territory developed acute-onset vertigo. Diffusion-weighted imaging revealed an
      acute infarction within the left posterior inferior cerebellar artery. His
      medical history was unremarkable except for hyperlipidemia; the initial
      examination revealed mild gait imbalance. During the 10 days of hospital
      admission, the patient experienced four recurrent ischemic strokes within the
      posterior circulation territory (occipital lobe, pons, and cerebellum). He was
      diagnosed with recurrent cerebral infarctions due to PACNS. The basilar artery
      exhibited no demonstrable luminal stenosis, but there were direct imaging signs
      of central nervous system angiitis including wall thickening and contrast
      enhancement. High-dose intravenous steroid therapy followed by oral prednisolone
      was administered. There was no further stroke recurrence and follow-up imaging of
      the arterial walls showed normalization of their characteristics. CONCLUSIONS:
      The present case emphasizes the importance of wall imaging in the diagnosis and
      treatment of PACNS.

PMID- 25045383
TI  - Opsoclonus-myoclonus syndrome associated with mumps virus infection.
AB  - BACKGROUND: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder
      that is characterized by involuntary eye movements and myoclonus. OMS exhibits
      various etiologies, including paraneoplastic, parainfectious, toxic-metabolic,
      and idiopathic causes. The exact immunopathogenesis and pathophysiology of OMS
      are uncertain. CASE REPORT: We report the case of a 19-year-old male who
      developed opsoclonus and myoclonus several days after a flu-like illness.
      Serological tests revealed acute mumps infection. The findings of cerebrospinal
      fluid examinations and brain magnetic resonance imaging were normal. During the
      early phase of the illness, he suffered from opsoclonus and myoclonus that was so
      severe as to cause acute renal failure due to rhabdomyolysis. After therapies
      including intravenous immunoglobulin, the patient gradually improved and had
      fully recovered 2 months later. CONCLUSIONS: This is the first report of OMS
      associated with mumps infection in Korea. Mumps infection should be considered in
      patients with OMS.

PMID- 25045384
TI  - A report of congestive myelopathy as a result of chronic chylous reflux syndrome.

PMID- 25045385
TI  - Comments on "unilateral reversible posterior leukoencephalopathy syndrome after
      coiling of an aneurysm".

PMID- 25045386
TI  - RE: Comments on "Unilateral Reversible Posterior Leukoencephalopathy Syndrome
      after Coiling of an Aneurysm": The Authors Respond.

PMID- 25045387
TI  - Effects of Wonli Acupuncture Procedure in Patients with LSS: A Clinical,
      Retrospective Study.
AB  - Background. Lumbar spinal stenosis (LSS) is a disease with increasing prevalence
      due to prolongation of average life span. Despite various treatment methods, many
      limitations remain unsolved. Objective. We are reporting cases of patients who
      have been treated with Wonli Acupuncture, a method of treating LSS by directly
      approaching the intervertebral foramen and interlaminar space with acupuncture
      needles different from those used in original acupuncture. Methods. A total of 82
      patients with LSS were treated with Wonli Acupuncture, and out of those, 47
      patients without exclusion criteria were selected for the following research. We
      compared the pretreatment VAS and ODI scores based on 1-year follow-up
      measurements. Results. The ODI value dropped by 15.3 +/- 24.8 on average (from
      35.2 +/- 19.9 at the baseline to 19.8 +/- 20.6 at the reading) (P < 0.01) and the
      average VAS also dropped by 19.2 +/- 37.2 (from 60.7 +/- 23.1 at baseline to 41.5
      +/- 31.9 at the reading) (P < 0.01). Conclusions. Wonli Acupuncture was found to
      have clinical efficacy for lumbar spinal stenosis. 

PMID- 25045388
TI  - Efficacy of herbal drugs in human diseases and disorders.

PMID- 25045389
TI  - Anti-inflammatory and antinociceptive activities of untreated, germinated, and
      fermented mung bean aqueous extract.
AB  - Evaluation of anti-inflammatory and antinociceptive activities of untreated mung
      bean (MB), germinated mung bean (GMB), and fermented mung bean (FMB) was
      performed on both in vitro (inhibition of inflammatory mediator, nitric
      oxide(NO)) and in vivo (inhibition of ear oedema and reduction of response to
      pain stimulus) studies. Results showed that both GMB and FMB aqueous extract
      exhibited potent anti-inflammatory and antinociceptive activities in a dose
      dependent manner. In vitro results showed that GMB and FMB were potent
      inflammatory mediator (NO) inhibitors at both 2.5 and 5 mg/mL. Further in vivo
      studies showed that GMB and FMB aqueous extract at 1000 mg/kg can significantly
      reduce ear oedema in mice caused by arachidonic acid. Besides, both 200 mg/kg and
      1000 mg/kg concentrations of GMB and FMB were found to exhibit potent
      antinociceptive effects towards hotplate induced pain. With these, it can be
      concluded that GMB and FMB aqueous extract exhibited potential anti-inflammatory
      and antinociceptive effects. 

PMID- 25045390
TI  - Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM)
      on Streptozotocin-Induced Diabetic Mice.
AB  - HEMOHIM (A NEW HERBAL PREPARATION OF THREE EDIBLE HERBS: Angelica gigas Nakai,
      Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect
      immune, hematopoietic, and self-renewal tissues against radiation. This study
      determined whether or not HemoHIM could alter hyperglycemia and the immune
      response in diabetic mice. Both nondiabetic and diabetic mice were orally
      administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by
      single injection of streptozotocin (STZ, 200 mg/kg, i.p.). In diabetic mice,
      HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the
      diabetic control group as well as elevated plasma insulin levels with
      preservation of insulin staining in pancreatic beta-cells. HemoHIM treatment
      restored thymus weight, white blood cells, lymphocyte numbers, and splenic
      lymphocyte populations (CD4(+) T and CD8(+) T), which were reduced in diabetic
      mice, as well as IFN-gamma production in response to Con A stimulation. These
      results indicate that HemoHIM may have potential as a glucose-lowering and
      immunomodulatory agent by enhancing the immune function of pancreatic beta-cells
      in STZ-induced diabetic mice.

PMID- 25045391
TI  - The Effects of Loranthus parasiticus on Scopolamine-Induced Memory Impairment in
      Mice.
AB  - This study is undertaken to evaluate cognitive enhancing effect and
      neuroprotective effect of Loranthus parasiticus. Cognitive enhancing effect of
      Loranthus parasiticus was investigated on scopolamine-induced amnesia model in
      Morris water maze test and passive avoidance test. We also examined the
      neuroprotective effect on glutamate-induced cell death in HT22 cells by MTT
      assay. These results of Morris water maze test and passive avoidance test
      indicated that 10 and 50 mg/kg of Loranthus parasiticus reversed scopolamine
      induced memory deficits. Loranthus parasiticus also protected against glutamate
      induced cytotoxicity in HT22 cells. As a result of in vitro test for elucidating
      possible mechanism, Loranthus parasiticus inhibited AChE activity, ROS
      production, and Ca(2+) accumulation. Loranthus parasiticus showed memory
      enhancing effect and neuroprotective effect and these effects may be related to
      inhibition of AChE activity, ROS level, and Ca(2+) influx. 

PMID- 25045392
TI  - Optimization of Phenolics Extracted from Idesia polycarpa Defatted Fruit Residue
      and Its Antioxidant and Depigmenting Activity In Vitro and In Vivo.
AB  - Extraction of phenolics from Idesia polycarpa defatted fruit residue was
      optimized by the maximization of the yield in total phenolics, using the response
      surface methodology. The optimized conditions were 50% ethanol, 5 h extraction
      time, 1 : 40 liquid to solid ratio, and 80 degrees C extraction temperature. The
      experimental average total phenolics yield was 54.49 +/- 4.26 mg/g. These
      antioxidant properties of phenolics were comprehensively analyzed for the first
      time. All the extracts not only demonstrated the significant free radical
      scavenging activities and metal chelating activity but also inhibited lipid,
      lipoprotein peroxidation and revealed reducing power activity. Ethyl acetate
      extraction (EAE) also inhibited mushroom tyrosinase activity and significantly
      increased the average skin-whitening index (L value) of the skin of C57BL/6 mice,
      indicating its potential use for skin hyperpigmentation in humans. The results of
      cell experiments showed EAE could strongly inhibit cellular tyrosinase activity,
      which had led to the decrease of melanogenesis in B16 mouse melanoma cells.
      Overall, EAE is an excellent natural antioxidant and depigmenting agent, which
      can be developed as a new food additive, medicine, and cosmetic. 

PMID- 25045393
TI  - Influence of herbal complexes containing licorice on potassium levels: a
      retrospective study.
AB  - To observe the influence of these complexes on potassium levels in a clinical
      setting, we investigated the influence of herbal complexes containing licorice on
      potassium levels. We retrospectively examined the medical records of patients
      treated with herbal complexes containing licorice from January 1, 2010, to
      December 31, 2010. We recorded the changes in the levels of potassium,
      creatinine, and blood urea nitrogen and examined the differences between before
      and after herbal complexes intake using a paired t-test. In addition, we
      investigated the prevalence of hypokalemia among these patients and reviewed such
      patients. We identified 360 patients who did not show significant changes in the
      levels of potassium and creatinine (P = 0.815, 0.289). We observed hypokalemia in
      6 patients. However, in 5 patients, the hypokalemia did not appear to be related
      to the licorice. Thus, we could suggest that herbal complexes containing licorice
      do not significantly influence the potassium levels in routine clinical herbal
      therapies. However, we propose that follow-up examination for potassium levels is
      required to prevent any unpredictable side effects of administration of licorice
      in routine herbal medicine care. 

PMID- 25045394
TI  - Acupuncture and multiple sclerosis: a review of the evidence.
AB  - Use of acupuncture to treat multiple sclerosis (MS) is fairly common, but little
      literature exists which studies its effectiveness. The purpose of this paper is
      to review the literature on the use of acupuncture to treat MS. A literature
      search resulted in twelve peer-reviewed articles on the subject that examined the
      use of acupuncture to treat MS related quality of life (QoL), fatigue,
      spasticity, and pain. The majority of the studies were poorly designed-without
      control, randomization, or blinding. Description of the subjects, interventions,
      and outcome measures as well as statistical analysis was often lacking or
      minimal. Although many of the studies suggested that acupuncture was successful
      in improving MS related symptoms, lack of statistical rigor and poor study design
      make it difficult to draw any conclusions about the true effectiveness of this
      intervention in the MS population. Further studies with more rigorous designs and
      analysis are needed before accurate claims can be made as to the effectiveness of
      acupuncture in this population. 

PMID- 25045395
TI  - 3D human motion editing and synthesis: a survey.
AB  - The ways to compute the kinematics and dynamic quantities of human bodies in
      motion have been studied in many biomedical papers. This paper presents a
      comprehensive survey of 3D human motion editing and synthesis techniques.
      Firstly, four types of methods for 3D human motion synthesis are introduced and
      compared. Secondly, motion capture data representation, motion editing, and
      motion synthesis are reviewed successively. Finally, future research directions
      are suggested. 

PMID- 25045396
TI  - Optimal installation locations for automated external defibrillators in Taipei 7
      Eleven stores: using GIS and a genetic algorithm with a new stirring operator.
AB  - Immediate treatment with an automated external defibrillator (AED) increases out
      of-hospital cardiac arrest (OHCA) patient survival potential. While considerable
      attention has been given to determining optimal public AED locations, spatial and
      temporal factors such as time of day and distance from emergency medical services
      (EMSs) are understudied. Here we describe a geocomputational genetic algorithm
      with a new stirring operator (GANSO) that considers spatial and temporal cardiac
      arrest occurrence factors when assessing the feasibility of using Taipei 7-Eleven
      stores as installation locations for AEDs. Our model is based on two AED
      conveyance modes, walking/running and driving, involving service distances of 100
      and 300 meters, respectively. Our results suggest different AED allocation
      strategies involving convenience stores in urban settings. In commercial areas,
      such installations can compensate for temporal gaps in EMS locations when
      responding to nighttime OHCA incidents. In residential areas, store installations
      can compensate for long distances from fire stations, where AEDs are currently
      held in Taipei. 

PMID- 25045397
TI  - 3D data denoising via Nonlocal Means filter by using parallel GPU strategies.
AB  - Nonlocal Means (NLM) algorithm is widely considered as a state-of-the-art
      denoising filter in many research fields. Its high computational complexity leads
      researchers to the development of parallel programming approaches and the use of
      massively parallel architectures such as the GPUs. In the recent years, the GPU
      devices had led to achieving reasonable running times by filtering, slice-by
      slice, and 3D datasets with a 2D NLM algorithm. In our approach we design and
      implement a fully 3D NonLocal Means parallel approach, adopting different
      algorithm mapping strategies on GPU architecture and multi-GPU framework, in
      order to demonstrate its high applicability and scalability. The experimental
      results we obtained encourage the usability of our approach in a large spectrum
      of applicative scenarios such as magnetic resonance imaging (MRI) or video
      sequence denoising. 

PMID- 25045398
TI  - Dosimetric algorithm to reproduce isodose curves obtained from a LINAC.
AB  - In this work isodose curves are obtained by the use of a new dosimetric algorithm
      using numerical data from percentage depth dose (PDD) and the maximum absorbed
      dose profile, calculated by Monte Carlo in a 18 MV LINAC. The software allows
      reproducing the absorbed dose percentage in the whole irradiated volume quickly
      and with a good approximation. To validate results an 18 MV LINAC with a whole
      geometry and a water phantom were constructed. On this construction, the distinct
      simulations were processed by the MCNPX code and then obtained the PDD and
      profiles for the whole depths of the radiation beam. The results data were used
      by the code to produce the dose percentages in any point of the irradiated
      volume. The absorbed dose for any voxel's size was also reproduced at any point
      of the irradiated volume, even when the voxels are considered to be of a pixel's
      size. The dosimetric algorithm is able to reproduce the absorbed dose induced by
      a radiation beam over a water phantom, considering PDD and profiles, whose
      maximum percent value is in the build-up region. Calculation time for the
      algorithm is only a few seconds, compared with the days taken when it is carried
      out by Monte Carlo. 

PMID- 25045399
TI  - Paraxial ocular measurements and entries in spectral and modal matrices: analogy
      and application.
AB  - Lensometers and keratometers yield powers along perpendicular meridians even if
      the principal meridians of the lens and the cornea are oblique. From each such
      instrument, multiple raw data represented on optical crosses require conversion
      to determine elementary statistics. Calculations for research decisions need to
      be authentic. Principles common to meridians generalize formulaic methods for
      oblique meridians. Like a lens or a cornea, matrix latent quantities are
      represented on a matrix cross. Our problem is to determine the matrix whose cross
      represents quantities on the optical cross. All measurements on an optical cross
      that include corneal and lens powers and oblique meridians can be considered.
      Once determined, a portfolio of matrix calculations applies and is justified for
      ophthalmic calculation. Matrices can be unique and, like a cornea before it is
      measured, contain latent observations. Asymmetric power component matrices
      quantify a deviation of a corneal surface from smoothness and toricity. Entries
      may identify those measurements causing irregular astigmatism that may stem from
      surgical or other external intervention. Irregular astigmatism is detected
      primarily from significant measurements in the paraxial range. Measurements are
      assimilated with matrix factors in a holistic way in order to support choices
      with calculations and statistics. 

PMID- 25045400
TI  - 3D alternating direction TV-based cone-beam CT reconstruction with efficient GPU
      implementation.
AB  - Iterative image reconstruction (IIR) with sparsity-exploiting methods, such as
      total variation (TV) minimization, claims potentially large reductions in
      sampling requirements. However, the computation complexity becomes a heavy
      burden, especially in 3D reconstruction situations. In order to improve the
      performance for iterative reconstruction, an efficient IIR algorithm for cone
      beam computed tomography (CBCT) with GPU implementation has been proposed in this
      paper. In the first place, an algorithm based on alternating direction total
      variation using local linearization and proximity technique is proposed for CBCT
      reconstruction. The applied proximal technique avoids the horrible pseudoinverse
      computation of big matrix which makes the proposed algorithm applicable and
      efficient for CBCT imaging. The iteration for this algorithm is simple but
      convergent. The simulation and real CT data reconstruction results indicate that
      the proposed algorithm is both fast and accurate. The GPU implementation shows an
      excellent acceleration ratio of more than 100 compared with CPU computation
      without losing numerical accuracy. The runtime for the new 3D algorithm is about
      6.8 seconds per loop with the image size of 256 * 256 * 256 and 36 projections of
      the size of 512 * 512. 

PMID- 25045401
TI  - Influence of surface topography on the human epithelial cell response to
      micropatterned substrates with convex and concave architectures.
AB  - BACKGROUND: Understanding the fundamental mechanisms underlying the cellular
      response to topographical surface features will extend our knowledge regarding
      the regulation of cell functions. Analyzing the cellular response to different
      topographical features, over multiple temporal and spatial scales, is central to
      understanding and guiding several biological functions. We used micropatterned
      substrates with convex and concave architectures to evaluate the behaviors of
      human epithelial cells on these substrates. RESULTS: Pillar and pit substrates
      caused heterogeneous spatial growth and distribution, with differences in cell
      density, over 48 h. Regional densities and distribution were significantly
      increased at pillar sidewalls, and at pit sidewalls and bottoms compared with
      those on flat unpatterned areas. Time-lapse observations revealed that different
      mechanisms of cell migration were dependent upon pillar and pit features. Cells
      on pillar substrate migrated towards the sidewall, whereas cells on pit substrate
      tended to move towards the sidewalls and bottom. Cytoskeletal staining of F-actin
      and vinculin showed that this migration can be attributed to difference in
      spatial reorganization of actin cytoskeleton, and the formation of focal
      adhesions at various points on the at the convex and concave corners of pillar
      and pit substrates. Cells cultured on the pillar substrate had stress fibers with
      extended filopodia and immature focal contacts at the sidewalls and convex
      corners, similar to those on the flat unpatterned substrate. Cells at the
      sidewalls and concave corners of pit substrate had more contractile stress fibers
      and stable focal contacts compared with cells on the pillar substrate. We also
      found that the substrate structures affect cell-cell contact formation via E
      cadherin, and that this was associated with reorganization of the actin
      cytoskeleton at the sidewall, and at the convex and concave corners of the
      substrate. CONCLUSION: Migration is an important factor affecting spatial growth
      and distribution. Heterogeneity at various locations was caused by different
      migratory behaviors at the convex and concave corners of pillar and pit
      substrates. We propose that this investigation is a valuable method for
      understanding cell phenotypes and the heterogeneity during spatial growth and
      distribution of epithelial cells during culture.

PMID- 25045402
TI  - Genetic counselors and the future of clinical genomics.
AB  - Barbara Bernhardt discusses how the increasing importance of genomics in the
      clinic will change the role of genetic counselors. 

PMID- 25045403
TI  - Proteochemometric modeling in a Bayesian framework.
AB  - Proteochemometrics (PCM) is an approach for bioactivity predictive modeling which
      models the relationship between protein and chemical information. Gaussian
      Processes (GP), based on Bayesian inference, provide the most objective
      estimation of the uncertainty of the predictions, thus permitting the evaluation
      of the applicability domain (AD) of the model. Furthermore, the experimental
      error on bioactivity measurements can be used as input for this probabilistic
      model. In this study, we apply GP implemented with a panel of kernels on three
      various (and multispecies) PCM datasets. The first dataset consisted of
      information from 8 human and rat adenosine receptors with 10,999 small molecule
      ligands and their binding affinity. The second consisted of the catalytic
      activity of four dengue virus NS3 proteases on 56 small peptides. Finally, we
      have gathered bioactivity information of small molecule ligands on 91 aminergic
      GPCRs from 9 different species, leading to a dataset of 24,593 datapoints with a
      matrix completeness of only 2.43%. GP models trained on these datasets are
      statistically sound, at the same level of statistical significance as Support
      Vector Machines (SVM), with [Formula: see text] values on the external dataset
      ranging from 0.68 to 0.92, and RMSEP values close to the experimental error.
      Furthermore, the best GP models obtained with the normalized polynomial and
      radial kernels provide intervals of confidence for the predictions in agreement
      with the cumulative Gaussian distribution. GP models were also interpreted on the
      basis of individual targets and of ligand descriptors. In the dengue dataset, the
      model interpretation in terms of the amino-acid positions in the tetra-peptide
      ligands gave biologically meaningful results. 

PMID- 25045404
TI  - A standard ballroom and Latin dance program to improve fitness and adherence to
      physical activity in individuals with type 2 diabetes and in obesity.
AB  - OBJECTIVE: To test the effectiveness of a dance program to improve fitness and
      adherence to physical activity in subjects with type 2 diabetes and obesity.
      RESEARCH DESIGN AND METHODS: Following a motivational interviewing session, 100
      subjects with diabetes and/or obesity were enrolled either in a dance program
      (DP, n = 42) or in a self-selected physical activity program (SSP, n = 58),
      according to their preferences. Outcome measures were reduced BMI/waist
      circumference, improved metabolic control in type 2 diabetes (-0.3% reduction of
      HbA1c) and improved fitness (activity expenditure >10 MET-hour/week; 10% increase
      in 6-min walk test (6MWT)). Target achievement was tested at 3 and 6 months,
      after adjustment for baseline data (propensity score). RESULTS: Attrition was
      lower in DP. Both programs significantly decreased body weight (on average, -2.6
      kg; P < 0.001) and waist circumference (DP, -3.2 cm; SSP, -2.2; P < 0.01) at 3
      months, and the results were maintained at 6 months. In DP, the activity-related
      energy expenditure averaged 13.5 +/- 1.8 MET-hour/week in the first three months
      and 14.1 +/- 3.0 in the second three-month period. In SSP, activity energy
      expenditure was higher but highly variable in the first three-month period (16.5
      +/- 13.9 MET-hour/week), and decreased in the following three months (14.2 +/-
      12.3; P vs. first period < 0.001). At three months, no differences in target
      achievement were observed between groups. After six months the odds to attain the
      MET, 6MWT and A1c targets were all significantly associated with DP. CONCLUSION:
      Dance may be an effective strategy to implement physical activity in motivated
      subjects with type 2 diabetes or obesity (Clinical trial reg. no.NCT02021890,
      clinicaltrials.gov).

PMID- 25045406
TI  - Potential effects of racial and ethnic disparities in meeting Medicare medication
      therapy management eligibility criteria.
AB  - OBJECTIVE: Medication therapy management (MTM) has the potential to play an
      instrumental role in reducing racial and ethnic disparities in health care.
      However, previous research has found that Blacks and Hispanics are less likely to
      be eligible for MTM. The purpose of the current study was to examine the
      potential effects of MTM eligibility criteria on racial and ethnic disparities in
      health outcomes. METHODS: The current study is a retrospective cross-sectional
      analysis of the Medicare Current Beneficiary Survey Cost and Use files for the
      years 2007 and 2008. A difference-in-differences model was used to compare
      disparities in outcomes between ineligible and eligible beneficiaries according
      to MTM eligibility criteria in 2010. This was achieved by including in regression
      models interaction terms between dummy variables for Blacks/Hispanics and MTM
      eligibility criteria. Interaction terms were interpreted on both multiplicative
      and additive terms. Various regression models were used depending on the types of
      variables. KEY FINDINGS: Whites were more likely to report self-perceived good
      health status than Blacks and Hispanics among both MTM-eligible and MTM
      ineligible populations. Disparities were greater among MTM-ineligible than MTM
      eligible populations (e.g., on additive term, difference in odds=1.94 and P<0.01
      for Whites and Blacks; difference in odds=2.86 and P<0.01 for Whites and
      Hispanics). A few other measures also exhibited significant patterns.
      CONCLUSIONS: MTM eligibility criteria may exacerbate racial and ethnic
      disparities in health status and some measures of health services utilizations
      and costs and medication utilization. Future research should examine strategies
      to remediate the effects of MTM eligibility criteria on disparities.

PMID- 25045405
TI  - Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer's
      disease immunotherapeutics.
AB  - Levels of amyloid-beta monomer and deposited amyloid-beta in the Alzheimer's
      disease brain are orders of magnitude greater than soluble amyloid-beta oligomer
      levels. Monomeric amyloid-beta has no known direct toxicity. Insoluble fibrillar
      amyloid-beta has been proposed to be an in vivo mechanism for removal of soluble
      amyloid-beta and exhibits relatively low toxicity. In contrast, soluble amyloid
      beta oligomers are widely reported to be the most toxic amyloid-beta form, both
      causing acute synaptotoxicity and inducing neurodegenerative processes. None of
      the amyloid-beta immunotherapies currently in clinical development selectively
      target soluble amyloid-beta oligomers, and their lack of efficacy is not
      unexpected considering their selectivity for monomeric or fibrillar amyloid-beta
      (or both) rather than soluble amyloid-beta oligomers. Because they exhibit acute,
      memory-compromising synaptic toxicity and induce chronic neurodegenerative
      toxicity and because they exist at very low in vivo levels in the Alzheimer's
      disease brain, soluble amyloid-beta oligomers constitute an optimal
      immunotherapeutic target that should be pursued more aggressively. 

PMID- 25045407
TI  - Unscheduled return visits to a Dutch inner-city emergency department.
AB  - BACKGROUND: Unscheduled return visits to the emergency department (ED) may
      reflect shortcomings in care. This study characterized ED return visits with
      respect to incidence, risk factors, reasons and post-ED disposition. We
      hypothesized that risk factors for unscheduled return and reasons for returning
      would differ from previous studies, due to differences in health care systems.
      METHODS: All unscheduled return visits occurring within 1 week and related to the
      initial ED visit were selected. Multivariable logistic regression was conducted
      to determine independent factors associated with unscheduled return, using
      patient information available at the initial visit. Reasons for returning
      unscheduled were categorized into illness-, patient- or physician-related. Post
      ED disposition was compared between patients with unscheduled return visits and
      the patients who did not return. RESULTS: Five percent (n = 2,492) of total ED
      visits (n = 49,341) were unscheduled return visits. Patients with an urgent
      triage level, patients presenting during the night shift, with a wound or local
      infection, abdominal pain or urinary problems were more likely to return
      unscheduled. Reasons to revisit unscheduled were mostly illness-related (49%) or
      patient-related (41%). Admission rates for returning patients (16%) were the same
      as for the patients who did not return (17%). CONCLUSIONS: Apart from abdominal
      complaints, risk factors for unscheduled return differ from previous studies.
      Short-term follow-up at the outpatient clinic or general practitioner for
      patients with urgent triage levels and suffering from wounds or local infections,
      abdominal pain or urinary problem might prevent unscheduled return.

PMID- 25045408
TI  - Associations between in-hospital bed occupancy and unplanned 72-h revisits to the
      emergency department: a register study.
AB  - BACKGROUND: A possible downstream effect of high in-hospital bed occupancy is
      that patients in the emergency department (ED) who would benefit from in-hospital
      care are denied admission. The present study aimed at evaluating this hypothesis
      through investigating associations between in-hospital bed occupancy at the time
      of presentation in the ED and the probability for unplanned 72-hour (72-h)
      revisits to the ED among patients discharged at index. A second outcome was
      unplanned 72-h revisits resulting in admission. METHODS: All visits to the ED of
      a 420-bed emergency hospital in southern Sweden between 1 January 2011 and 31
      December 2012, which did not result in admission, death, or transfer to another
      hospital were included. Revisiting fractions were computed for in-hospital
      occupancy intervals <85%, 85% to 90%, 90% to 95%, 95% to 100%, 100% to 105%, and
      >=105%. Multivariate models were constructed in an attempt to take confounding
      factors from, e.g., presenting complaints, age, referral status, and triage
      priority into account. RESULTS: Included in the study are 81,878 visits. The
      fraction of unplanned 72-h revisits/unplanned 72-h revisits resulting in
      admission was 5.8%/1.4% overall, 6.2%/1.4% for occupancy <85%, 6.4%/1.5% for
      occupancy 85% to 90%, 5.8%/1.4% for occupancy 90% to 95%, 6.0%/1.6% for occupancy
      95% to 100%, 5.4%/1.6% for occupancy 100% to 105%, and 4.9%/1.4% for occupancy
      >=105%. In the multivariate models, a trend to lower probability of unplanned 72
      h revisits was observed at occupancy >=105% compared to occupancy <95% (OR 0.88,
      CI 0.76 to 1.01). No significant associations between in-hospital occupancy at
      index and the probability of making unplanned 72-h revisits resulting in
      admission were observed. CONCLUSIONS: The lack of associations between in
      hospital occupancy and unplanned 72-h revisits does not support the hypothesis
      that ED patients are inappropriately discharged when in-hospital beds are scarce.
      The results are reassuring as they indicate that physicians are able to make good
      decisions, also while resources are constrained.

PMID- 25045409
TI  - Environmental contaminants perturb fragile protein assemblies and inhibit normal
      protein function.
AB  - The molecular mechanisms whereby small molecules that contaminate our environment
      cause physiological effects are largely unknown, in terms of both targets and
      mechanisms. The essential human enzyme porphobilinogen synthase (HsPBGS, a.k.a. 5
      aminolevulinate dehydratase, ALAD) functions in heme biosynthesis. HsPBGS
      catalytic activity is regulated allosterically via an equilibrium of inactive
      hexamers and active octamers, and we have shown that certain drugs and drug-like
      small molecules can inhibit HsPBGS in vitro by stabilizing the hexamer. Here we
      address whether components of the National Toxicology Program library of
      environmental contaminants can stabilize the HsPBGS hexamer and inhibit activity
      in vitro. Native polyacrylamide gel electrophoresis was used to screen the
      library (1,408 compounds) for components that alter the oligomeric distribution
      of HsPBGS. Freshly purchased samples of 37 preliminary hits were used to confirm
      the electrophoretic results and to determine the dose-dependence of the
      perturbation of oligomeric distribution. Seventeen compounds were identified
      which alter the oligomeric distribution toward the hexamer and also inhibit
      HsPBGS catalytic activity, including the most potent HsPBGS inhibitor yet
      characterized (Mutagen X, IC50 = 1.4 MUM). PBGS dysfunction is associated with
      the inborn error of metabolism know as ALAD porphyria and with lead poisoning.
      The identified hexamer-stabilizing inhibitors could potentiate these diseases.
      Allosteric regulation of activity via an equilibrium of alternate oligomers has
      been proposed for many proteins. Based on the precedent set herein, perturbation
      of these oligomeric equilibria by small molecules (such as environmental
      contaminants) can be considered as a mechanism of toxicity.

PMID- 25045410
TI  - Autonomy and Enhancement.
AB  - Some have objected to human enhancement on the grounds that it violates the
      autonomy of the enhanced. These objections, however, overlook the interesting
      possibility that autonomy itself could be enhanced. How, exactly, to enhance
      autonomy is a difficult problem due to the numerous and diverse accounts of
      autonomy in the literature. Existing accounts of autonomy enhancement rely on
      narrow and controversial conceptions of autonomy. However, we identify one
      feature of autonomy common to many mainstream accounts: reasoning ability.
      Autonomy can then be enhanced by improving people's reasoning ability, in
      particular through cognitive enhancement; given how valuable autonomy is usually
      taken to be, this gives us extra reason to pursue such cognitive enhancements.
      Moreover, autonomy-based objections will be especially weak against such
      enhancements. As we will argue, those who are worried that enhancements will
      inhibit people's autonomy should actually embrace those enhancements that will
      improve autonomy.

PMID- 25045411
TI  - Ethical, Political and Societal Implications of the Open Access Journal Movement
      in the Era of Economic Crisis, with Emphasis on Public Health Pharmacogenomics.
AB  - Publication of the research outputs is a vital step of the research processes and
      a gateway between the laboratory and the global society. Open Access is
      revolutionizing the dissemination of scientific ideas, particularly in the field
      of public health pharmacogenomics that examines the ways in which
      pharmacogenomics impacts health systems and services at a societal level, rather
      than a narrow bench to bedside model of translation science. This manuscript
      argues that despite some limitations and drawbacks, open access has profound
      ethical, political and societal implications especially on underdeveloped and
      developing countries, and that it provides opportunities for science to grow in
      these resource-limited countries, particularly in the era of a severe economic
      and financial crisis that is imposing cuts and restrictions to research.

PMID- 25045412
TI  - Rounded atelectasis of the lung: A pictorial review.
AB  - Rounded atelectasis of the lung is well described in medical literature, but
      still difficult to diagnose. Since lesions give no clinical symptoms in patients,
      radiologists are often the first to recognize the round lesion in an X-ray
      picture or a CT scan. Rounded atelectasis is an atypical form of lung collapse
      that usually occurs adjacent to scarred pleura and can be mistaken for lung
      cancer. Patients with rounded atelectasis have a history of asbestos exposure or
      pleural effusion due to various causes. When characteristic imaging findings are
      present, the diagnosis is rarely dubious and no further investigation is
      necessary. However, differential diagnosis of rounded atelectasis poses a
      challenge to pulmonary specialists and radiologists. 

PMID- 25045413
TI  - Peripheral primitive neuroectodermal tumor of the dura in a 51-year-old woman
      following intensive treatment for breast cancer.
AB  - PATIENT: Female, 51. FINAL DIAGNOSIS: Ewing sarcoma. SYMPTOMS: Visual
      disturbances. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: Oncology.
      OBJECTIVE: Rare disease. BACKGROUND: Primitive neuroectodermal tumor/Ewing
      sarcoma (PNET/EWS) is a round blue cell sarcoma that shows varying degrees of
      neuroectodermal differentiation. PNET/EWS as a primary intracranial tumor is
      extremely uncommon. CASE REPORT: We report a unique case of peripheral PNET
      presenting as an intracranial mass in an adult following chemotherapy and
      radiotherapy for a solid tumor. A 51-year-old woman with previously treated left
      breast cancer was evaluated for a newly developed brain mass. She underwent
      craniotomy with resection. Surgical pathology was consistent with a peripheral
      PNET/EWS with Ewing sarcoma gene translocation. She was treated appropriately
      with vincristine, cyclophosphamide, and doxorubicin (later dactinomycin)
      alternating with ifosfamide and etoposide. CONCLUSIONS: Although development of
      PNET/EWS presenting along the CNS is exceedingly rare in adults, establishing the
      proper diagnosis of this "small blue cell tumor" is critical. The further
      distinction between central PNET and peripheral PNET can greatly impact both
      prognosis and treatment. Our case also highlights the importance of considering
      the impact of prior intensive therapies, including radiation and chemotherapy, on
      predisposing to future PNET/EWS.

PMID- 25045416
TI  - Changes in Anger in Relationship to Responsivity to PTSD Treatment.
AB  - This study examined the clinical course of different dimensions of anger and
      their relationship to change in posttraumatic stress disorder (PTSD) in a sample
      of 139 female survivors of interpersonal violence suffering from PTSD.
      Specifically, this study evaluated differences in the rates of change in anger
      dimensions by responsivity to treatment status (responders, non-responders, and
      drop-outs). Responders and non-responders did not differ in rate of change on
      state anger and anger directed inward, suggesting that treatment led to
      improvements in these dimensions of anger regardless of final PTSD diagnosis.
      Responders did evidence statistically significantly more change in trait anger
      and control over one's anger than did the non-responders, suggesting that changes
      in these dimensions of anger may be related to recovery from PTSD. Individuals
      who terminated therapy prematurely did not experience the same gains in state
      anger, trait anger, or anger-in as those who completed treatment. Differences in
      rates of change (linear versus quadratic growth patterns), particularly with
      respect to continued improvement in anger following treatment completion are
      discussed.

PMID- 25045415
TI  - Circulating levels of sirtuin 4, a potential marker of oxidative metabolism,
      related to coronary artery disease in obese patients suffering from NAFLD, with
      normal or slightly increased liver enzymes.
AB  - The present study shows low circulating levels of SIRT4 in obese patients with
      nonalcoholic fatty liver disease mirroring its reduced mitochondrial expression
      in an attempt to increase the fat oxidative capacity and then the mitochondrial
      function in liver and in muscle. SIRT4 modulates the metabolism of free fatty
      acids reducing their high circulating levels but, unfortunately, increasing ROS
      production. Great concentration of free fatty acids, released by adipose tissue,
      coupled with oxidative stress, directly results in endothelial dysfunction, early
      atherosclerosis, and coronary artery disease risk factor. 

PMID- 25045414
TI  - Dietary Lycium barbarum polysaccharide induces Nrf2/ARE pathway and ameliorates
      insulin resistance induced by high-fat via activation of PI3K/AKT signaling.
AB  - Lycium barbarum polysaccharide (LBP), an antioxidant from wolfberry, displays the
      antioxidative and anti-inflammatory effects on experimental models of insulin
      resistance in vivo. However, the effective mechanism of LBP on high-fat diet
      induced insulin resistance is still unknown. The objective of the study was to
      investigate the mechanism involved in LBP-mediated phosphatidylinositol 3-kinase
      (PI3K)/AKT/Nrf2 axis against high-fat-induced insulin resistance. HepG2 cells
      were incubated with LBP for 12 hrs in the presence of palmitate. C57BL/6J mice
      were fed a high-fat diet supplemented with LBP for 24 weeks. We analyzed the
      expression of nuclear factor-E2-related factor 2 (Nrf2), Jun N-terminal kinases
      (JNK), and glycogen synthase kinase 3beta (GSK3beta) involved in insulin
      signaling pathway in vivo and in vitro. First, LBP significantly induced
      phosphorylation of Nrf2 through PI3K/AKT signaling. Second, LBP obviously
      increased detoxification and antioxidant enzymes expression and reduced reactive
      oxygen species (ROS) levels via PI3K/AKT/Nrf2 axis. Third, LBP also regulated
      phosphorylation levels of GSK3beta and JNK through PI3K/AKT signaling. Finally,
      LBP significantly reversed glycolytic and gluconeogenic genes expression via the
      activation of Nrf2-mediated cytoprotective effects. In summary, LBP is novel
      antioxidant against insulin resistance induced by high-fat diet via activation of
      PI3K/AKT/Nrf2 pathway. 

PMID- 25045417
TI  - A Diagnosis of Maxillary Sinus Fracture with Cone-Beam CT: Case Report and
      Literature Review.
AB  - The purpose of this article is to present the case of maxillofacial trauma
      patient with maxillary sinus fracture diagnosed with cone-beam computed
      tomography (CBCT) and to explore the applications of this technique in evaluating
      the maxillofacial region. A 23-year-old male patient attempted to our clinic who
      had an injury at midface with complaints of swelling, numbness. The patient was
      examined before in emergency center but any diagnosis was made about the
      maxillofacial trauma. The patient re-examined clinically and radiographically. A
      fracture on the frontal wall of maxillary sinus is determined with the aid of
      CBCT. The patient consulted with the department of maxillofacial surgery and it
      is decided that any surgical treatment was not necessary. The emerging technique
      CBCT would not be the primary choice of imaging maxillofacial trauma.
      Nevertheless, when advantages considered this imaging procedure could be the
      modality of choice according to the case. 

PMID- 25045418
TI  - Treatment effects of dexmedetomidine and ketamine on postoperative analgesia
      after cleft palate repair.
AB  - Primary cleft palate repair may result in significant pain in the immediate
      postoperative period, which can lead to vigorous crying resulting in wound
      dehiscence and pulmonary complications. Effective pain control with opioids is
      the mainstay but administration on the floor has to be countered with the
      complications associated with their use, chiefly respiratory depression and
      sedation. We retrospectively examined the efficacies of intraoperative
      administration of intravenous (IV) dexmedetomidine (DEX) and ketamine (KET) to
      prevent early postoperative pain in children undergoing primary cleft palate
      repair and compared the results against relevant literature. The Texas Children's
      Hospital anesthesia database was queried to identify children undergoing a
      palatal surgery from December 2011 to December 2012. Inclusion criteria permitted
      completed primary palatal surgery without major complications and intraoperative
      administration of DEX or KET. The control group (CTRL) received no additional
      drug. A comprehensive literature review was performed. A total of 71 pediatric
      patients underwent palatal surgery during the study period with 46 patients
      qualifying for analysis. Although results were not significant, consistent trends
      were observed with regards to lower opioid requirements during the first 24 hours
      for both medications compared with the CTRL. KET also had shorter time to
      discharge. The literature review resulted in several studies supporting decreased
      postoperative pain end points for both DEX and KET. In our sample, DEX and KET
      reduced postoperative opioid requirements. KET seems to have the added benefit of
      a shorter hospital stay. These finding are supported in the literature. With
      further investigation, the addition of these drugs may serve to provide improved
      pain relief without over sedation in patients undergoing cleft palate repair. 

PMID- 25045419
TI  - Retained broken implants in the craniomaxillofacial skeleton.
AB  - Facial fracture patients are seen in a Level 1 trauma hospital. In our
      institution, we manage many patients with facial fractures and carry out more
      than 150 surgical procedures every year. Open reduction and internal fixation is
      our management of choice. All surgical procedures involve drilling of bone and
      implant insertion to keep the fractured bones in an anatomically reduced position
      to aid healing. Occasionally, drill bits used to create the pilot hole break and
      are embedded in the bone. We present a situation in which such an incident
      occurred and review the literature on retained broken implants and devices. 

PMID- 25045420
TI  - Computer-Assisted Mandibular Reconstruction using a Patient-Specific
      Reconstruction Plate Fabricated with Computer-Aided Design and Manufacturing
      Techniques.
AB  - We investigated the workflow of computer-assisted mandibular reconstruction that
      was performed with a patient-specific mandibular reconstruction plate fabricated
      with computer-aided design and computer-aided manufacturing (CAD/CAM) techniques
      and a fibula flap. We assessed the feasibility of this technique from virtual
      planning to the completion of surgery. Computed tomography (CT) scans of a
      cadaveric skull and fibula were obtained for the virtual simulation of mandibular
      resection and reconstruction using ProPlan CMF software (Materialise((r))/DePuy
      Synthes((r))). The virtual model of the reconstructed mandible provided the basis
      for the computer-aided design of a patient-specific reconstruction plate that was
      milled from titanium using a five-axis milling machine and CAM techniques.
      CAD/CAM techniques were used for producing resection guides for mandibular
      resection and cutting guides for harvesting a fibula flap. Mandibular
      reconstruction was simulated in a cadaveric wet laboratory. No problems were
      encountered during the procedure. The plate was fixed accurately to the residual
      bone without difficulty. The fibula segments were attached to the plate rapidly
      and reliably. The fusion of preoperative and postoperative CT datasets
      demonstrated high reconstruction precision. Computer-assisted mandibular
      reconstruction with CAD/CAM-fabricated patient-specific reconstruction plates
      appears to be a promising approach for mandibular reconstruction. Clinical trials
      are required to determine whether these promising results can be translated into
      successful practice and what further developments are needed. 

PMID- 25045421
TI  - Gap Junction Enhancer Potentiates Cytotoxicity of Cisplatin in Breast Cancer
      Cells.
AB  - Cisplatin is one of the most widely used anti-cancer drugs due to its ability to
      damage DNA and induce apoptosis. However, increasing reports of side effects and
      drug resistance indicate the limitation of cisplatin in cancer therapeutics.
      Recent studies showed that inhibition of gap junctions diminishes the cytotoxic
      effect and contributes to drug resistance. Therefore, identification of molecules
      that counteract gap junctional inhibition without decreasing the anti-cancer
      effect of cisplatin could be used in combinational treatment, potentiating
      cisplatin efficacy and preventing resistance. This study investigates the effects
      of combinational treatment of cisplatin and PQ1, a gap junction enhancer, in T47D
      breast cancer cells. Our results showed that combinational treatment of PQ1 and
      cisplatin increased gap junctional intercellular communication (GJIC) as well as
      expressions of connexins (Cx26, Cx32 and Cx43), and subsequently decreased cell
      viability. Ki67, a proliferation marker, was decreased by 75% with combinational
      treatment. Expressions of pro-apoptotic factors (cleaved caspase-3/-8/-9 and bax)
      were increased by the combinational treatment with PQ1 and cisplatin; whereas,
      the pro-survival factor, bcl-2, was decreased by the combinational treatment. Our
      study demonstrates for the first time that the combinational treatment with gap
      junction enhancers can counteract cisplatin induced inhibition of gap junctional
      intercellular communication and reduction of connexin expression, thereby
      increasing the efficacy of cisplatin in cancer cells.

PMID- 25045422
TI  - A stepped-care model of post-disaster child and adolescent mental health service
      provision.
AB  - BACKGROUND: From a global perspective, natural disasters are common events.
      Published research highlights that a significant minority of exposed children and
      adolescents develop disaster-related mental health syndromes and associated
      functional impairment. Consistent with the considerable unmet need of children
      and adolescents with regard to psychopathology, there is strong evidence that
      many children and adolescents with post-disaster mental health presentations are
      not receiving adequate interventions. OBJECTIVE: To critique existing child and
      adolescent mental health services (CAMHS) models of care and the capacity of such
      models to deal with any post-disaster surge in clinical demand. Further, to
      detail an innovative service response; a child and adolescent stepped-care
      service provision model. METHOD: A narrative review of traditional CAMHS is
      presented. Important elements of a disaster response - individual versus
      community recovery, public health approaches, capacity for promotion and
      prevention and service reach are discussed and compared with the CAMHS approach.
      RESULTS: Difficulties with traditional models of care are highlighted across all
      levels of intervention; from the ability to provide preventative initiatives to
      the capacity to provide intense specialised posttraumatic stress disorder
      interventions. In response, our over-arching stepped-care model is advocated. The
      general response is discussed and details of the three tiers of the model are
      provided: Tier 1 communication strategy, Tier 2 parent effectiveness and teacher
      training, and Tier 3 screening linked to trauma-focused cognitive behavioural
      therapy. CONCLUSION: In this paper, we argue that traditional CAMHS are not an
      appropriate model of care to meet the clinical needs of this group in the post
      disaster setting. We conclude with suggestions how improved post-disaster child
      and adolescent mental health outcomes can be achieved by applying an innovative
      service approach.

PMID- 25045424
TI  - Urodynamic study of bladder function following nerve sparing radical
      hysterectomy.

PMID- 25045423
TI  - Contributing role of extracellular vesicles on vascular endothelium haemostatic
      balance in cancer.
AB  - Extracellular vesicles (EVs) generated during tumourigenesis are thought to play
      a major role in the hypercoagulant state observed in cancer patients. They
      exhibit negatively charged phospholipids and tissue factor (TF) that promote
      coagulation cascade activation. In addition, they contain surface proteins and
      cytoplasmic molecules, both originating from the producing cell that can impact
      target cells' expression. By targeting endothelial cells of blood vessels, these
      EVs could disturb the physiological anticoagulant properties of these cells and
      be partly responsible for the vascular endothelium activation observed in cancer
      patients. Indeed, vascular endothelium naturally exhibits heparin-like
      proteoglycan, TF pathway inhibitor and protein C anticoagulant pathway that
      prevent thrombosis in physiological condition. An overexpression of TF and a
      decreased expression of coagulation cascade inhibitors have been reported after
      EVs' treatment of endothelial cells. The induction of apoptosis and an increased
      expression of platelet adhesion molecules have also been highlighted. These
      events may promote thrombus formation in cancer. The aim of this paper is to
      provide a targeted review on the current evidence and knowledge of roles and
      impact of EVs on endothelial surface anticoagulant and procoagulant factors and
      cellular adhesion molecules expression. 

PMID- 25045425
TI  - Shall we settle for low-level evidence?

PMID- 25045426
TI  - Conservative treatment for atypical endometrial hyperplasia: what is the most
      effective therapeutic method?

PMID- 25045427
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health.

PMID- 25045428
TI  - Laparoscopic surgery for early ovarian cancer.

PMID- 25045429
TI  - Trends in gynecologic cancer mortality in East Asian regions.
AB  - OBJECTIVE: To evaluate uterine and ovarian cancer mortality trends in East Asian
      countries. METHODS: For three Asian countries and one region (Japan, Korea,
      Singapore, and Hong Kong), we extracted number of deaths for each year from the
      World Health Organization (WHO) mortality database, focusing on women >=20 years
      old. The WHO population data were used to estimate person-years at risk for
      women. The annual age-standardized, truncated rates were evaluated for four age
      groups. We also compared age-specific mortality rates during three calendar
      periods (1979 to 1988, 1989 to 1998, and 1999 to 2010). Joinpoint regression was
      used to determine secular trends in mortality. To obtain cervical and uterine
      corpus cancer mortality rates in Korea, we re-allocated the cases with uterine
      cancer of unspecified subsite according to the proportion in the National Cancer
      Incidence Databases. RESULTS: Overall, uterine cancer mortality has decreased in
      each of the Asian regions. In Korea, corrected cervical cancer mortality has
      declined since 1993, at an annual percentage change (APC) of -4.8% (95%
      confidence interval [CI], -5.3 to -4.4). On the other hand, corrected uterine
      corpus cancer mortality has abruptly increased since 1995 (APC, 6.7; 95% CI, 5.4
      to 8.0). Ovarian cancer mortality was stable, except in Korea, where mortality
      rates steadily increased at an APC of 6.2% (95% CI, 3.4 to 9.0) during 1995 to
      2000, and subsequently stabilized. CONCLUSION: Although uterine cancer mortality
      rates are declining in East Asia, additional effort is warranted to reduce the
      burden of gynecologic cancer in the future, through the implementation of early
      detection programs and the use of optimal therapeutic strategies.

PMID- 25045430
TI  - Condom and oral contraceptive use and risk of cervical intraepithelial neoplasia
      in Australian women.
AB  - OBJECTIVE: To assess the association between condom use and oral contraceptive
      consumption and the risk of cervical intraepithelial neoplasia (CIN). METHODS: A
      cross-sectional study was conducted in Perth clinics. A total of 348 women
      responded to the structured questionnaire. Information sought included
      demographic and lifestyle characteristics such as the use of condom for
      contraception, consumption of oral contraceptive, and duration of oral
      contraceptive usage. Crude and adjusted odds ratio (OR) and associated 95%
      confidence interval (CI) were calculated using unconditional logistic regression
      models and reported as estimates of the relative risk. RESULTS: The prevalence of
      CIN was found to be 15.8%. The duration of oral contraceptive consumption among
      women with abnormal Papanicolaou (Pap) smear result indicating CIN was
      significantly shorter than those without abnormal Pap smear result (mean+/-SD,
      5.6+/-5.2 years vs. 8.2+/-7.6 years; p=0.002). Comparing to <=3 years usage,
      prolonged consumption of oral contraceptive for >=10 years reduced the risk of
      CIN (p=0.012). However, use of condom for contraception might not be associated
      with a reduced risk of CIN after accounting for the effects of confounding
      factors (adjusted OR, 0.52; 95% CI, 0.05 to 5.11; p=0.577). CONCLUSION: Use of
      oral contraceptives, but not condoms, for contraception appeared to be inversely
      associated with CIN. Prolonged use of oral contraceptive demonstrated its
      benefits of reducing the risk of CIN.

PMID- 25045431
TI  - Factors associated with future commitment and past history of human papilloma
      virus vaccination among female college students in northern Taiwan.
AB  - OBJECTIVE: To investigate factors influencing commitment to human papilloma virus
      (HPV) vaccination and prior vaccination among female college students in northern
      Taiwan. METHODS: A quota sample of 400 female college students was recruited from
      nine colleges in northern Taiwan during March 2013. Of these, 398 completed the
      self administered questionnaire which was designed based on the health promotion
      model. RESULTS: The results showed that factors associated with prior vaccination
      behavior were family history of gynecologic malignancy, ever being advised to get
      HPV vaccination, perceived barriers of action and perceived self-efficacy.
      Predictors for commitment to HPV vaccination in the next 6 months were the cost
      of vaccination, ever being advised to get HPV vaccination, perceived self
      efficacy and situational influences. Perceived self-efficacy was significantly
      influenced by relationship status, past receipt of a recommendation for HPV
      vaccination and level of knowledge about HPV. CONCLUSION: When formulating
      vaccination policies, governmental or medical institutions should include these
      factors to promote vaccination.

PMID- 25045432
TI  - Various types of total laparoscopic nerve-sparing radical hysterectomies and
      their effects on bladder function.
AB  - OBJECTIVE: This study was conducted to ascertain the correlation between
      preserved pelvic nerve networks and bladder function after laparoscopic nerve
      sparing radical hysterectomy. METHODS: Between 2009 and 2011, 53 patients
      underwent total laparoscopic radical hysterectomies. They were categorized into
      groups A, B, and C based on the status of preserved pelvic nerve networks:
      complete preservation of the pelvic nerve plexus (group A, 27 cases); partial
      preservation (group B, 13 cases); and complete sacrifice (group C, 13 cases). To
      evaluate bladder function, urodynamic studies were conducted preoperatively and
      postoperatively at 1, 3, 6, and 12 months after surgery. RESULTS: No significant
      difference in sensory function was found between groups A and B. However, the
      sensory function of group C was significantly lower than that of the other
      groups. Group A had significantly better motor function than groups B and C. No
      significant difference in motor function was found between groups B and C.
      Results showed that the sensory nerve is distributed predominantly at the dorsal
      half of the pelvic nerve networks, but the motor nerve is predominantly
      distributed at the ventral half. CONCLUSION: Various types of total laparoscopic
      nerve-sparing radical hysterectomies can be tailored to patients with cervical
      carcinomas.

PMID- 25045433
TI  - Ultrasound guided conformal brachytherapy of cervix cancer: survival, patterns of
      failure, and late complications.
AB  - OBJECTIVE: The aim of this study was to report on the long-term results of
      transabdominal ultrasound guided conformal brachytherapy in patients with
      cervical cancer with respect to patterns of failures, treatment related
      toxicities and survival. METHODS: Three hundred and nine patients with cervical
      cancer who presented to Institute between January 1999 and December 2008 were
      staged with magnetic resonance imaging and positron emission tomography and
      treated with external beam radiotherapy and high dose rate conformal image guided
      brachytherapy with curative intent. Follow-up data relating to sites of failure
      and toxicity was recorded prospectively. RESULTS: Two hundred and ninety-two
      patients were available for analyses. The median (interquantile range) follow-up
      time was 4.1 years (range, 2.4 to 6.1 years). Five-year failure free survival and
      overall survival (OS) were 66% and 65%, respectively. Primary, pelvic, para
      aortic, and distant failure were observed in 12.5%, 16.4%, 22%, and 23% of
      patients, respectively. In multivariate analysis, tumor volume and nodal disease
      related to survival, whereas local disease control and point A dose did not.
      CONCLUSION: Ultrasound guided conformal brachytherapy of cervix cancer has led to
      optimal local control and OS. The Melbourne protocol compares favorably to the
      more technically elaborate and expensive GEC-ESTRO recommendations. The Melbourne
      protocol's technical simplicity with real-time imaging and treatment planning
      makes this a method of choice for treating patients with cervical cancer.

PMID- 25045434
TI  - Conservative therapy with metformin plus megestrol acetate for endometrial
      atypical hyperplasia.
AB  - OBJECTIVE: To compare the efficacy of metformin plus megestrol acetate (MA) with
      that of MA alone for treating endometrial atypical hyperplasia (EAH). METHODS:
      This pilot study included 16 EAH patients who met at least one metabolic syndrome
      (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA
      monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily,
      whereas patients in the MET group received the same dose of MA plus 0.5 g of
      metformin thrice daily. Treatment response was assessed by histological
      examination of dilation and curettage specimens obtained after 12 weeks of
      therapy. RESULTS: Each group had eight patients, and half of the patients in each
      group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in
      the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did
      not affect the response rates in either group. In the MET group, 75% (3/4) of the
      patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of
      the patients with MS had CR, whereas no patient without MS had CR. No
      irreversible toxicities were observed. CONCLUSION: Metformin plus MA may be a
      potential alternative therapy for treating EAH, and the MS status of patients may
      have no effect on the efficacy of metformin plus MA therapy.

PMID- 25045435
TI  - Overexpression of the epithelial cell adhesion molecule is associated with a more
      favorable prognosis and response to platinum-based chemotherapy in ovarian
      cancer.
AB  - OBJECTIVE: Epithelial cell adhesion molecule (EpCAM) has experienced a
      renaissance lately as a binding site for targeted therapy as well as a prognostic
      marker in epithelial malignancies. Aim of this study was to study EpCAM as a
      potential prognostic marker in epithelial ovarian cancer (EOC). METHODS: EpCAM
      expression was assessed by immunohistochemistry on paraffin-embedded primary EOC
      tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76%
      to 100%. Tissue samples and clinical data were systematically collected within
      the international and multicenter "Tumorbank Ovarian Cancer" network. RESULTS:
      Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in
      the study (median age, 56 years; range, 31 to 86 years). The majority of the
      patients (81.1%) presented with an advanced stage International Federation of
      Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type
      in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%).
      EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly
      more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant
      difference was noted between the other histological subgroups. EpCAM
      overexpression was significantly associated with a better progression free
      survival and higher response rates to platinum based chemotherapy (p=0.040 and
      p=0.048, respectively). EpCAM was identified as an independent prognostic marker
      for overall survival (p=0.022). CONCLUSION: Our data indicate a significant
      association of EpCAM overexpression with a more favorable survival in EOC
      patients. Serous cancers showed a significant EpCAM overexpression compared to
      mucinous types. Larger multicenter analyses are warranted to confirm these
      findings.

PMID- 25045436
TI  - Prevention of lymphocele development in gynecologic cancers by the electrothermal
      bipolar vessel sealing device.
AB  - OBJECTIVE: A number of new techniques have been developed to prevent lymphocele
      formation after pelvic lymphadenectomy in gynecologic cancers. We assessed
      whether the electrothermal bipolar vessel sealing device (EBVSD) could decrease
      the incidence of postoperative lymphocele secondary to pelvic lymphadenectomy.
      METHODS: A total of 321 patients with gynecologic cancer underwent pelvic
      lymphadenectomy from 2005 to 2011. Pelvic lymphadenectomy without EBVSD was
      performed in 134 patients, and pelvic lymphadenectomy with EBVSD was performed in
      187 patients. We retrospectively compared the incidence of lymphocele and
      symptoms between both groups. RESULTS: Four to 8 weeks after operation, 108 cases
      of lymphocele (34%) were detected by computed tomography scan examination. The
      incidence of lymphocele after pelvic lymphadenectomy was 56% (75/134) in the tie
      ligation group, and 18% (33/187) in the EBVSD group. We found a statistically
      significant difference in the incidence of lymphocele between both groups
      (p<0.01). To detect the independent risk factor for lymphocele development, we
      performed multivariate analysis with logistic regression for three variables
      (device, number of dissected lymph nodes, and operation time). Among these
      variables, we found a significant difference (p<0.001) for only one device.
      CONCLUSION: Use of the EBVSD during gynecological cancer operation is useful for
      preventing the development of lymphocele secondary to pelvic lymphadenectomy.

PMID- 25045437
TI  - Major clinical research advances in gynecologic cancer in 2013.
AB  - In 2013, 10 topics were selected for major clinical research advances in
      gynecologic oncology; these included three topics regarding cervical cancer,
      three regarding ovarian cancer, two regarding endometrial cancer, and one each
      regarding breast cancer and radiation oncology. For cervical cancer, bevacizumab
      was first demonstrated to exhibit outstanding clinical efficacy in a recurrent,
      metastatic setting. Regarding cervical cancer screening, visual inspections with
      acetic acid in low-resource settings, p16/Ki-67 double staining, and the follow
      up results of four randomized controlled trials of human papillomavirus-based
      screening methods were reviewed. Laparoscopic para-aortic lymphadenectomy before
      chemoradiation for locally advanced cervical cancer was the final topic for
      cervical cancer. Regarding front-line ovarian cancer therapies, dose-dense
      paclitaxel and carboplatin, intraperitoneal chemotherapy, and other targeted
      agents administered according to combination or maintenance schedules were
      discussed. Regarding recurrent ovarian cancer treatment, cediranib, olaparib, and
      farletuzumab were discussed for platinum-sensitive disease. The final overall
      survival data associated with a combination of bevacizumab and chemotherapy for
      platinum-resistant disease were briefly summarized. For endometrial cancer, the
      potential clinical efficacy of metformin, an antidiabetic drug, in obese patients
      was followed by integrated genomic analyses from the Cancer Genome Atlas Research
      Network. For breast cancer, three remarkable advances were reviewed: the long
      term effects of continued adjuvant tamoxifen for 10 years, the effects of 2-year
      versus 1-year adjuvant trastuzumab for human epidermal growth factor receptor 2
      positive disease, and the approval of pertuzumab in a neoadjuvant setting with a
      pathologic complete response as the surrogate endpoint. Finally, the recent large
      studies of intensity-modulated radiotherapy for gynecologic cancer were briefly
      summarized. 

PMID- 25045440
TI  - KJU indexed in MEDLINE.

PMID- 25045438
TI  - Beyond angiogenesis blockade: targeted therapy for advanced cervical cancer.
AB  - The global burden of advanced stage cervical cancer remains significant,
      particular in resource poor countries where effective screening programs are
      absent. Unfortunately, a proportion of patients will be diagnosed with advanced
      stage disease, and may suffer from persistent or recurrent disease despite
      treatment with combination chemotherapy and radiation. Patients with recurrent
      disease have a poor salvage rate, with an expected 5-year survival of less than
      10%. Recently, significant gains have been made in the antiangiogenic arena;
      nonetheless the need to develop effective alternate targeted strategies is
      implicit. As such, a review of molecular targeted therapy in the treatment of
      this disease is warranted. In an era of biologics, combined therapy with
      cytotoxic drugs and molecular targeted agents, represents an exciting arena yet
      to be fully explored. 

PMID- 25045441
TI  - Clinical use of [-2]proPSA (p2PSA) and its derivatives (%p2PSA and Prostate
      Health Index) for the detection of prostate cancer: a review of the literature.
AB  - Prostate-specific antigen (PSA) is recognized as an organ-specific marker with
      low specificity and sensitivity in discriminating prostate cancer (PCa) from
      other benign conditions, such as prostatic hyperplasia or chronic prostatitis.
      Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a
      prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as
      a new marker to accurately detect PCa. The aim of this systematic review was to
      discuss the available literature regarding the clinical validity and utility of
      p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index
      (PHI). A systematic search of the PubMed and Scopus electronic databases was
      performed in accordance with the PRISMA statement (http://www.prisma
      statement.org), considering the time period from January 1990 to January 2014 and
      using the following search terms: proprostate specific antigen, proenzyme PSA,
      proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies
      have been published, but only 35 were considered for the qualitative analysis.
      These studies suggested that p2PSA is the most cancer-specific form of PSA, being
      preferentially expressed in PCa tissue and being significantly elevated in the
      serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements
      improve the specificity of the available tests (PSA and derivatives) in detecting
      PCa. Moreover, increasing PHI values seem to correlate with more aggressive
      disease. Some studies have compared p2PSA and its derivatives with other new
      biomarkers and found p2PSA to be significantly more accurate. Indeed, the
      implementation of these tests in clinical practice has the potential to
      significantly increase the physician's ability to detect PCa and avoid
      unnecessary biopsies, while also having an effective impact on costs. Further
      studies in large, multicenter, prospective trials are required to confirm these
      encouraging results on the clinical utility of these new biomarkers.

PMID- 25045442
TI  - The type of nephrectomy has little effect on overall survival or cardiac events
      in patients of 70 years and older with localized clinical t1 stage renal masses.
AB  - PURPOSE: To compare the outcomes of nephron-sparing options (e.g., partial
      nephrectomy [PN]) and low-surgical-morbidity options (e.g., radical nephrectomy
      [RN]) in elderly patients with limited life expectancy. MATERIALS AND METHODS: We
      retrospectively reviewed 135 patients aged 70 years or older who underwent RN
      (n=82) or PN (n=53) for clinical T1 stage renal masses between January 2000 and
      December 2012. Clinicopathologic data were thoroughly analyzed and compared
      between the RN and PN groups. The modification of diet in renal disease equation
      was used to estimate glomerular filtration. Overall survival and cardiac events
      were assessed by using Kaplan-Meier survival analysis and Cox proportional
      hazards regression modeling. RESULTS: Over a median follow-up period of 59.72
      months, 17 patients (20.7%) in the RN group and 3 patients (5.7%) in the PN group
      died. Chronic kidney disease (<60 mL/min/1.73 m(2)) developed more frequently in
      RN patients than in PN patients (75.6% vs. 41.5%, p<0.001). The 5-year overall
      survival rate did not differ significantly between the RN and PN groups (90.7%
      vs. 93.8%; p=0.158). According to the multivariate analysis, the Charlson
      comorbidity index score was an independent predictor of overall survival (hazard
      ratio [HR], 2.679, p=0.037). Type of nephrectomy was not significantly associated
      with overall survival (HR, 2.447; p=0.167) or cardiac events (HR, 1.147;
      p=0.718). CONCLUSIONS: Although chronic kidney disease was lower after PN,
      overall survival and cardiac events were similar regardless of type of
      nephrectomy.

PMID- 25045444
TI  - Factors influencing the acceptance of transrectal ultrasound-guided prostate
      biopsies.
AB  - PURPOSE: This study aimed to improve prostate biopsy compliance by analyzing the
      factors that influence the acceptance of prostate biopsy by patients to whom
      transrectal ultrasound (TRUS)-guided prostate biopsy is recommended for suspected
      prostate cancer. MATERIALS AND METHODS: The subjects of this study were 268
      patients to whom TRUS-guided prostate biopsy was recommended from January to June
      2011 and who completed a questionnaire. Patients who showed a prostate-specific
      antigen (PSA) increase to more than 4.0 ng/mL or abnormal findings on a digital
      rectal examination and TRUS were recommended to undergo prostate biopsy. The
      questionnaire consisted of 9 questions about the subjects' demographic
      characteristics and 15 questions that assessed their knowledge of prostate
      disease. Fisher exact probability test was conducted to assess the influence of
      the demographic characteristics and levels of knowledge of prostate disease on
      acceptance of prostate biopsy. RESULTS: The mean age of the subjects was 66.2
      years (range, 43-83 years). Of the cohort, 188 patients (70.7%) agreed to the
      prostate biopsy and 78 patients (29.3%) refused. In terms of demographic
      characteristics, the patients' acceptance of prostate biopsy was associated only
      with education level. Patients with relatively lower education levels had a
      higher acceptance rate for prostate biopsy (80.0% vs. 65.9%, p=0.018). Other
      demographic factors, as well as the degree of knowledge of prostate disease, had
      no significant effect on the acceptance rate. CONCLUSIONS: The patients'
      acceptance of prostate biopsy can be influenced by demographic characteristics,
      especially education level. Therefore, when prostate biopsy is recommended to
      patients, their demographic characteristics should be taken into consideration.

PMID- 25045443
TI  - Predictors of intravesical recurrence after radical nephroureterectomy for upper
      urinary tract urothelial carcinoma: an inflammation-based prognostic score.
AB  - PURPOSE: Systemic inflammatory responses, which are defined in terms of the
      Glasgow prognostic score (GPS), have been reported to be independent predictors
      of unfavorable outcomes in various human cancers. We assessed the utility of the
      GPS as a predictor of intravesical recurrence after radical nephroureterectomy
      (RNU) in upper urinary tract carcinoma (UTUC). MATERIALS AND METHODS: We
      collected data for 147 UTUC patients with no previous history of bladder cancer
      who underwent RNU from 2004 to 2012. Associations between perioperative
      clinicopathological variables and intravesical recurrence were analyzed by using
      univariate and multivariate Cox regression models. RESULTS: Overall, 71 of 147
      patients (48%) developed intravesical recurrence, including 21 patients (30%)
      diagnosed with synchronous bladder tumor. In the univariate analysis, performance
      status, diabetes mellitus (DM), serum albumin, C-reactive protein, GPS, and
      synchronous bladder tumor were associated with intravesical recurrence. In the
      multivariate analysis, performance status (hazard ratio [HR], 2.33; 95%
      confidence interval [CI], 1.41-3.85; p=0.001), DM (HR, 2.04; 95% CI, 1.21-3.41;
      p=0.007), cortical thinning (HR, 2.01; 95% CI, 1.08-3.71; p=0.026), and GPS
      (score of 1: HR, 6.86; 95% CI, 3.69-12.7; p=0.001; score of 2: HR, 5.96; 95% CI,
      3.10-11.4; p=0.001) were independent predictors of intravesical recurrence.
      CONCLUSIONS: Our results suggest that the GPS as well as performance status, DM,
      and cortical thinning are associated with intravesical recurrence after RNU.
      Thus, more careful follow-up, coupled with postoperative intravesical therapy to
      avoid bladder recurrence, should be considered in these patients.

PMID- 25045445
TI  - Is there an association between serum prostate-specific antigen values and serum
      testosterone levels in healthy men?
AB  - PURPOSE: To evaluate the relationship between levels of total testosterone and
      total prostate-specific antigen (PSA) in healthy men with PSA<4 ng/mL. MATERIALS
      AND METHODS: The study comprised 179 men with a mean age of 59.19+/-12 years who
      visited Osmaniye State Hospital, Osmaniye, Turkey, between January 2006 and
      January 2007 for a routine checkup. The patients were divided into two subgroups:
      patients with PSA<2.5 mg/ml (group I, n=160 patients) and patients with PSA of
      2.5 to 4 ng/mL (group II, n=19 patients). The relationship between PSA and
      testosterone levels was investigated in both groups and in patients aged <60
      years. The mean testosterone level was calculated for patients aged <50 years and
      was compared with the mean value of patients aged >=50 years. RESULTS: In all
      patients, the mean values for serum PSA and total testosterone were 1.27+/-0.88
      ng/mL and 404.04+/-158.86 ng/mL, respectively. No correlation was detected
      between serum PSA and testosterone levels in either subgroup (group I, r=0.072,
      p=0.363; group II, r=0.031, p=0.900) or in patients aged <60 years (r=0.032,
      p=0.72). The mean values of testosterone in patients aged >=50 years and in
      patients aged <50 years were 417.01+/-163.35 and 344.16+/-120.21 ng/dL,
      respectively (p=0.02). CONCLUSIONS: No impact of testosterone was found on the
      PSA level in healthy men with PSA <4 ng/mL. Therefore, a high serum testosterone
      level may not mandate adjustment of PSA values. This serum sex hormone showed a
      significant increment after the age of 50 years. Further studies including a
      larger number of patients should be carried out to confirm these findings.

PMID- 25045446
TI  - Prostate volume measurement by transrectal ultrasonography: comparison of height
      obtained by use of transaxial and midsagittal scanning.
AB  - PURPOSE: The purpose of this study was to compare prostate volume measured by
      transrectal ultrasonography (TRUS) between transaxial scanning and midsagittal
      scanning. We tried to determine which method is superior. MATERIALS AND METHODS:
      A total of 968 patients who underwent TRUS for diagnosis of any diseases related
      to the prostate were included in this study. When measuring prostate volume by
      TRUS, we conducted the measurements two ways at the same time in all patients: by
      use of height obtained by transaxial scanning and by use of height obtained by
      midsagittal scanning. Prostate volume was calculated by using the ellipsoid
      formula ([height*length*width]*pi/6). RESULTS: For prostate volume measured by
      TRUS, a paired t-test revealed a significant difference between using height
      obtained by transaxial scanning and that obtained by midsagittal scanning in all
      patients (28.5+/-10.1 g vs. 28.7+/-9.9 g, respectively, p=0.004). However, there
      were no significant differences in the prevalence of prostate volume more than 20
      g (known benign prostatic enlargement [BPE]) between the two methods by chi
      square test (90.5% [n=876], 90.8% [n=879], respectively; p=0.876). When analyzed
      in the same way, there were no significant differences in the prevalence of
      prostate volume more than 30 g (generally, high-risk BPE) between the two methods
      (34.5% [n=334], 36.3% [n=351], respectively; p=0.447). CONCLUSIONS: Although
      prostate volume by TRUS differed according to the method used to measure height,
      that is, transaxial or midsagittal scanning, we conclude that there are no
      problems in diagnosing BPE clinically by use of either of the two methods.

PMID- 25045447
TI  - Laparoscopic stone surgery with the aid of flexible nephroscopy.
AB  - PURPOSE: To report the outcome of laparoscopic pyelo- and ureterolithotomies with
      the aid of flexible nephroscopy. MATERIALS AND METHODS: A retrospective analysis
      was performed in 71 patients with complex renal stones or large and impacted
      proximal ureteral stones. Patients underwent laparoscopic pyelo- or
      ureterolithotomies with or without the removal of small residual stones by use of
      flexible nephroscopy between July 2005 and July 2010. Operative success was
      defined as no residual stones in the intravenous pyelogram at 12 weeks
      postoperatively. Perioperative results and surgical outcomes were analyzed.
      RESULTS: The patients' mean age was 54.7+/-13.7 years, and 53 males (74.6%) and
      18 females (25.4%) were included. The mean maximal stone size was 19.4+/-9.4 mm.
      A total of 47 cases were complex renal stones and 24 cases were impacted ureteral
      stones. Mean operative time was 139.0+/-63.7 minutes. Stones were completely
      removed in 61 cases (85.9%), and no further ancillary treatment was needed for
      clinically insignificant residual fragments in 7 cases (9.9%). For complex renal
      stones, the complete stone-free rate and clinically significant stone-free rate
      were 80.9% and 93.6%, respectively. Multivariate analysis showed that the use of
      flexible nephroscopy for complex renal stones can reduce the risk of residual
      stones. A major complication occurred in one case, in which open conversion was
      performed. CONCLUSIONS: Laparoscopic stone surgery is a safe and minimally
      invasive procedure with a high success rate, especially with the aid of flexible
      nephroscopy, and is not associated with procedure-specific complications.

PMID- 25045448
TI  - Relationship between uncommon computed tomography findings and clinical aspects
      in patients with acute pyelonephritis.
AB  - PURPOSE: Computed tomography (CT) has become popular in the diagnosis of acute
      pyelonephritis (APN) and its related complications in adults. The aim of this
      study was to investigate the relationship between uncommon CT findings and
      clinical and laboratory data in patients with APN. MATERIALS AND METHODS: From
      July 2009 to July 2012, CT findings and clinical data were collected from 125
      female patients with APN. The six uncommon CT findings (excluding a wedge-shaped
      area of hypoperfusion in the renal parenchyma) studied were perirenal fat
      infiltration, ureteral wall edema, renal abscess formation, pelvic ascites,
      periportal edema, and renal scarring. The clinical parameters analyzed were the
      age and body mass index of the patients as well as the degree and duration of
      fever. Laboratory parameters related to inflammation and infection included white
      blood cell count, C-reactive protein (CRP) level, erythrocyte sedimentation rate,
      pyuria, and bacteriuria. RESULTS: The most common CT finding was perirenal fat
      infiltration (69 cases, 55%). A longer duration of fever, higher CRP level, and
      grade of pyuria were related with perirenal fat infiltration (p=0.010, p=0.003,
      and p=0.049, respectively). The CRP level was significantly higher in patients
      with renal abscess and ureteral wall edema (p=0.005 and p=0.015, respectively).
      CONCLUSIONS: The uncommon CT findings that were related to aggravated clinical
      and laboratory parameters of APN patients were perirenal fat infiltration,
      ureteral wall edema, and renal abscess formation. The inflammatory reaction and
      tissue destruction may be more aggressive in patients with these CT findings.

PMID- 25045449
TI  - Growth inhibition after exposure to transforming growth factor-beta1 in human
      bladder cancer cell lines.
AB  - PURPOSE: Transforming growth factor-beta1 (TGF-beta1) plays a dual role in
      apoptosis and in proapoptotic responses in the support of survival in a variety
      of cells. The aim of this study was to determine the function of TGF-beta1 in
      bladder cancer cells. MATERIALS AND METHODS: The role of TGF-beta1 in bladder
      cancer cells was examined by observing cell viability by using the tetrazolium
      dye (MTT) assay after treating the bladder cancer cell lines 253J, 5637, T24,
      J82, HT1197, and HT1376 with TGF-beta1. Among these cell lines, the 253J and T24
      cell lines were coincubated with TGF-beta1 and the pan anti-TGF-beta antibody.
      Fluorescence-activated cell sorter (FACS) analysis was performed to determine the
      mechanism involved after TGF-beta1 treatment in 253J cells. RESULTS: All six cell
      lines showed inhibited cellular growth after TGF-beta1 treatment. Although the
      T24 and J82 cell lines also showed inhibited cellular growth, the growth
      inhibition was less than that observed in the other 4 cell lines. The addition of
      pan anti-TGF-beta antibodies to the culture media restored the growth properties
      that had been inhibited by TGF-beta1. FACS analysis was performed in the 253J
      cells and the 253J cells with TGF-beta1. There were no significant differences in
      the cell cycle between the two treatments. However, there were more apoptotic
      cells in the TGF-beta1-treated 253J cells. CONCLUSIONS: TGF-beta1 did not
      stimulate cellular proliferation but was a growth inhibitory factor in bladder
      cancer cells. However, the pattern of its effects depended on the cell line. TGF
      beta1 achieved growth inhibition by enhancing the level of apoptosis.

PMID- 25045450
TI  - Laparoscopic management of a hydatid cyst of the adrenal gland.
AB  - Hydatid disease is endemic in parts of India, yet genitourinary involvement is
      rare. Laparoscopic management of such cases is uncommonly reported. We present a
      case of an adrenal hydatid and its management by laparoscopic aspiration,
      instillation of scolicidal solution, and partial excision of the cyst.

PMID- 25045451
TI  - Vesicoenteric fistula due to bladder squamous cell carcinoma.
AB  - Vesicoenteric fistula is a rare complication of bladder squamous cell carcinoma.
      We report the case of a 70-year-old male who complained of painless, total gross
      hematuria. Abdominopelvic computed tomography (CT) revealed an approximately 2.7
      cm lobulated and contoured enhancing mass in the bladder dome. We performed
      partial cystectomy of the bladder dome after transurethral resection of the
      bladder. The biopsy result was bladder squamous cell carcinoma, with infiltrating
      serosa histopathologically, but the resection margin was free. Postoperatively,
      follow-up CT was done after 3 months. Follow-up CT revealed an approximately 4.7
      cm*4.0-cm lobulated, contoured, and heterogeneous mass in the bladder dome. A
      vesicoenteric fistula was visible by cystography. Here we report this case of a
      vesicoenteric fistula due to bladder squamous cell carcinoma.

PMID- 25045453
TI  - Comparison of Antimicrobial Sensitivity to Older and Newer Quinolones versus
      Piperacillin-Tazobactam, Cefepime and Meropenem in Febrile Patients with Cancer
      in two Referral Pediatric Centers in Tehran, Iran.
AB  - BACKGROUND: Infection in pediatric cancer patients has become a concerning
      problem due to increasing antimicrobial resistance. The goal of this study was to
      determine the antimicrobial resistance patterns of blood isolates from pediatric
      oncology patients in Iran to determine if there was significant resistance to
      quinolones. METHODS: Children with cancer who were admitted with or developed
      fever during admission to Aliasghar Children's Hospital or Mahak Hospitals July
      2009 through June 2011 were eligible for enrollment. Two blood cultures were
      obtained. Antimicrobial sensitivity test was performed for ciprofloxacin,
      moxifloxacin, gatifloxacin, meropenem, cefepime, and piperacillin-tazobactam on
      isolates from children who were bacteremic. RESULTS: Blood cultures were positive
      for 38 episodes in 169 enrolled children but 9 episodes were excluded as blood
      cultures were thought to be contaminated, yielding a bacteremia rate of 29/160
      (18%). The mean age of children and the stage of malignancy did not differ
      between those with and without bacteremia. Meropenem was the most likely
      antibiotic to cover isolates (97%) with cefepime having the lowest coverage rate
      (21%). Quinolone coverage ranged from 63% to 76%. CONCLUSION: Quinolones may not
      be suitable for use as empiric therapy in febrile pediatric oncology patients in
      Iran.

PMID- 25045452
TI  - Clinical significance of assessment of thrombospondin and placenta growth factor
      levels in patients with sickle cell anemia: two centers egyptian studies.
AB  - BACKGROUND: Sickle cell disease has a worldwide distribution. Vaso-occlusive
      crisis (VOC) is one of the most important clinical features of the disease.
      Thrombospondin (TSP1) and Placenta growth factor (PlGF) have been reported to be
      involved in sickle cell diseases (SCD). OBJECTIVE: The aim of this study was to
      assess the clinical significance of Thrombospondin and Placenta growth factor
      profiles in patients with sickle cell disease. PATIENTS AND METHODS: This study
      was carried out in sixty patients with sickle cell anemia who were attendants to
      Hematology units, Pediatric Departments, Tanta and Elmenofia University Hospitals
      in the period between December 2011 and May 2014 including thirty patients during
      vaso-occlusive crisis and thirty patients out of crisis. Also this study included
      twenty healthy children of matched age and sex as a control group. Serum TSP1 and
      PlGF levels were analyzed by ELISA. RESULTS: In SCA patients with crisis the mean
      serum Thrombospondin level was 902.5+/-280.89 ng/mL; in SCA patients out of
      crisis the mean serum Thrombospondin level was 462.5 +/- 190.2 ng/mL and in
      controls the mean value was 236.66+/-58.29 ng/mL. In SCA patients with crisis the
      mean serum Placenta growth factor level was 19.97+/-1.28 pg/ml; in SCA patients
      out of crisis the mean serum Placenta growth factor level was 13.12 +/- 1.82
      pg/ml and in controls the mean value was 9.89 +/- 1.20 pg/ml. All paired
      comparisons for Thrombospondin and Placenta growth factor reached statistical
      significance (P< 0.001). There was significant positive correlation between serum
      Thrombospondin and Placenta growth factor levels in sickle cell anemia patients
      during crisis (r=0.848, p=<0.001). CONCLUSIONS: This is the first study to show
      TSP1and PlGF concentration changes in patients with SCD in a large cohort study
      from Middle East, and to show correlation between both markers; therefore TSP1and
      PlGF may be useful VOC markers in SCD patients. RECOMMENDATION: To further assess
      TSP1 and PlGF as a marker of VOC in patients with SCD, further studies should be
      conducted to determine the exact point before VOC, when serum TSP1 and PIGF
      levels begin to increase. This requires monitoring of the TSP1 and PIGF levels in
      sickle cell patients out of crisis, showing how rapidly these levels increase
      just before VOC development.

PMID- 25045454
TI  - Cost of hematopoietic stem cell transplantation in India.
AB  - Hematopoietic stem cell transplantation (HSCT) is a definite cure for many
      hematological diseases. With the increasing indications for HSCT and its
      relatively low cost in Indian subcontinent, an increasing number of patients are
      opting for this procedure. We retrospectively analyzed the cost of one hundred
      sixty two HSCTs done at our center in the last three years. The median cost of
      autologous transplant was USD, $ 12,500 (range $ 10,331-39,367) and the median
      cost of allogeneic transplant was $ 17,914 (range $ 10,832-44,701). The cost of
      HSCT is cheaper here compared to that in developed countries and success rates
      are nearly equivalent. The major factors contributing to the cost are related to
      the complications post-transplant mainly infections and graft versus host
      disease, which are also the reasons for the increased stay in the hospital. 

PMID- 25045455
TI  - Autologous Hematopoietic Stem Cell Transplantation for High-risk Acute
      Lymphoblastic Leukemia: non-Randomized Study with a maximum Follow-up of more
      than 22 Years.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of autologous hematopoietic stem
      cell transplantation (AHSCT) for high-risk acute lymphoblastic leukemia (ALL).
      MATERIAL AND METHODS: Overall, 128 high-risk ALL patients at a median age of 26
      years (range 18-56 years) at diagnosis received AHSCT between 1991-2008.
      Induction treatment was anthracycline-based in all patients. Conditioning regimen
      consisted of CAV (cyclophosphamide, cytarabine, etoposide) in 125 patients
      whereas 3 subjects received cyclophosphamide and TBI (total body irradiation).
      Bone marrow was stored for 72 hours in 4 degrees C and re-infused 24 hours after
      conditioning completion. Bone marrow was a source of stem cells in 119 patients,
      peripheral blood in 2 and 7 subjects received both bone marrow and peripheral
      blood. RESULTS: With a median follow-up after AHSCT of 1.6 years (range 0.1-22.3
      years), the probability of leukemia-free survival (LFS) for the whole group at 10
      years was 27% and 23% at 20 years. Transplant-related mortality at 100 days after
      AHSCT was 3.2%. There was a strong tendency for better LFS for MRD-negative
      patients if compared with patients who had positive or unknown MRD status at
      AHSCT (32% vs 23% and 25%, respectively; p=0.06). There was no difference in LFS
      between B- and T-lineage ALL as well as between patients transplanted in first
      complete remission (CR1) and CR2. LFS at 10 years for patients with Philadelphia
      positive (Ph+) ALL at transplant was 20% and this was comparable with subjects
      with negative and missing Ph status (26% and 28%; p=0.97). CONCLUSIONS: The
      results of AHSCT for high-risk ALL remains unsatisfactory with low probability of
      long-term LFS.

PMID- 25045456
TI  - Epidemiological Overview of Hodgkin Lymphoma across the Mediterranean Basin.
AB  - The epidemiology of Hodgkin lymphoma (HL) has always been a source of fascination
      to researchers due to its heterogeneous characteristics of presentation. HL is an
      uncommon neoplasm of B-cell origin with an incidence that varies significantly by
      age, sex, ethnicity, geographic location and socioeconomic status. This complex
      pattern was also found to be replicated among Mediterranean basin populations. HL
      incidence rates progressively decreased from industrialized European countries
      such as France (ASR=2.61) and Italy (ASR=2.39) to less developed nations such as
      Albania (ASR=1.34) and Bosnia Herzegovina (ASR=1.1). Regarding HL mortality we
      have found that countries with the lowest incidence rates show the highest number
      of deaths from this cancer and viceversa. Finally, a wide gap in terms of
      survival was showed across the Mediterranean basin with survival rates ranged
      from 82.3% and 85.1% among Italian men and women, to 53.3 % and 59.3% among
      Libyan men and women, respectively. Factors such as the degree of socio-economic
      development, the exposure to risk factors westernization-related, the
      availability of diagnostic practices along with different genetic
      susceptibilities to HL may explain its variation across Mediterranean countries.
      Furthermore, the lack of health resources decisively contribute to the poor
      prognosis recorded in less developed region. In the future, the introduction of
      appropriate and accessible treatment facilities along with an adequate number of
      clinical specialists in the treatment of HL and other cancers are warranted in
      order to improve the outcomes of affected patients and treat a largely curable
      type of cancer in disadvantaged regions. 

PMID- 25045457
TI  - Short term advantages of a public-private partnership for tuberculosis in Guinea
      bissau: reduction of mortality and increased diagnostic capacity.
AB  - BACKGROUND: Tuberculosis (TB) is widespread in Africa, but weak health systems in
      developing countries, often display poor quality of care with delays in case
      identification, irrational therapy and drug shortage, clinical mismanagement,
      unnecessary expenditures for patients, reduced adherence and increased mortality.
      Public-private partnership has demonstrated to increase TB case detection, but
      less is known about its effects on quality of care, mortality and costs for
      hospitalized TB patients. METHODS: Clinical outcomes and costs for TB patients at
      the TB National Reference Center of Bissau, in Guinea Bissau, West Africa, were
      determined during the first 5 months of the public-private management and
      compared to the ones of previous years when the hospitals was under direct
      Government's management. RESULTS: 215 (2009-2010) and 194 (2012-2013) patients
      were admitted, respectively. Improvement (p<0.05) was observed in mortality
      reduction (21% vs 6%), cause of death determination (50% vs 85%), treatment
      abandonment (15 vs 1). Direct costs for patients during TB diagnostic pathway and
      inpatient care were significantly reduced, 475 vs. 0 USD. CONCLUSIONS: Public
      private partnerships displays significant short term benefits in National TB
      reference centers, even in post-conflict countries. Further studies could aid in
      determining the overall long term benefits of this type of cooperation, and the
      specific characteristic of TB and concomitant hematologic and infectious diseases
      in TB admitted patients.

PMID- 25045458
TI  - Hodgkin's Lymphoma in Older Patients: an Orphan Disease?
AB  - Hodgkin Lymphoma HL can be cured in the large majority of younger patients, but
      prognosis for older patients, especially those with advanced-stage disease, has
      not improved substantially. The percentage of HL patients aged over 60 ranges
      between 15% and 35%. A minority of them is enrolled into clinical trials. HL in
      the elderly have some specificities: more frequent male sex, B-symptoms, advanced
      stage, sub diaphragmatic presentation, higher percentage of mixed cellularity, up
      to 50% of advanced cases associated to EBV. Very old age (>70) and comorbidities
      are factor of further worsening prognosis. Like in younger patients, ABVD is the
      most used protocol, but treatment outcome remains much inferior with more
      frequent, severe and sometimes specific toxicities. Few prospective studies with
      specific protocols are available. The main data have been published by the
      Italian Lymphoma Group with the VEPEMB schedule and the German Hodgkin Study
      Group with the PVAG regimen. Recently, the Scotland and Newcastle Lymphoma Study
      Group published the SHIELD program associating a prospective phase 2 trial with
      VEPEMB and a prospective registration of others patients. Patients over 60y with
      early-stage disease received three cycles plus radiotherapy and had 81% of 3-year
      overall survival (OS). Those with advanced-stage disease received six cycles,
      with 3-year OS of 66%. The role of geriatric and comorbidity assessment in the
      treatment's choice for HL in the elderly is a major challenge. The combination of
      loss of activities of daily living combined with the age stratification more or
      less 70y has been shown as a simple and effective survival model. Hopes come from
      promising new agents like brentuximab-vedotin (BV) a novel antibody-drug
      conjugate. The use of TEP to adapt the combination of chemotherapy and
      radiotherapy according to the metabolic response could also be way for
      prospective studies. 

PMID- 25045459
TI  - A Case of Iron Deficiency Anemia with Co-existing Hb Fontainebleau.
AB  - Hb Fontainebleau is a rare alpha chain variant in the Indian population which
      generates an unknown peak on hemoglobin HPLC study and does cause diagnostic
      difficulty to those who are not acquainted with this entity. We present a case of
      Hb Fontainebleau, an eighteen year old patient who presented with symptoms
      related to anemia to our department and unknown peak observed in HPLC plots lead
      us to family study and molecular characterization for this case. 

PMID- 25045460
TI  - Treatment of adolescent and young adults with acute lymphoblastic leukemia.
AB  - The primary objective of this review was to update and discuss the current
      concepts and the results of the treatment of acute lymphoblastic leukemia (ALL)
      in adolescents and young adults (AYA). After a brief consideration of the
      epidemiologic and clinicobiologic characteristics of ALL in the AYA population,
      the main retrospective comparative studies stating the superiority of pediatric
      over adult-based protocols were reviewed. The most important prospective studies
      in young adults using pediatric inspired or pediatric unmodified protocols were
      also reviewed emphasizing their feasibility at least up to the age of 40 yr and
      their promising results, with event-free survival rates of 60-65% or greater.
      Results of trials from pediatric groups have shown that the unfavourable
      prognosis of adolescents is no more adequate. The majority of the older
      adolescents with ALL can be cured with risk-adjusted and minimal residual disease
      guided intensive chemotherapy, without stem cell transplantation. However, some
      specific subgroups, which are more frequent in adolescents than in children
      (e.g., early pre-T, iAMP21, and BCR-ABL-like), deserve particular attention. In
      summary, the advances in treatment of ALL in adolescents have been translated to
      young adults, and that explains the significant improvement in survival of these
      patients in recent years. 

PMID- 25045461
TI  - Prognostic factors in hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is among the neoplastic diseases that has the best long
      term outcome after cytotoxic treatment. Cure rates approach 80-90%; however, 15
      20% of patients will be resistant to therapy (primary refractory) or relapse
      after treatment. Prognostic factors should help to stratify treatment according
      to the risk profile and identify patients at risk for failure. Significance of
      prognostic factors partly depends on the efficacy of the treatments administered,
      since new effective therapies can variably counterbalance the adverse effects of
      some unfavorable clinical determinants. As a consequence, some prognostic factors
      thought to be important in the past may become meaningless when modern successful
      therapies are used. Therefore, the value of prognostic factors has to be updated
      periodically, and then adapted to new emerging biomarkers. Besides the prognostic
      role of PET imaging, tissue and circulating biomarkers, as the number of tumor
      infiltrating macrophages, cytokine and chemokine levels and profiling of
      circulating nucleic acids (DNA and microRNAs) have shown promise. 

PMID- 25045462
TI  - Reduction of intramedullary apoptosis after stem cell transplantation in black
      african variant of pediatric sickle cell anemia.
AB  - BACKGROUND AND PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT)
      is the only curative treatment for sickle cell anemia (SCA). We report our
      experience with transplantation in children with the Black African variant of SCA
      and the effects of transplant on erythroid compartment in bone marrow (BM).
      PATIENTS AND METHODS: Twenty-seven consecutive patients who underwent BM
      transplantation from HLA-identical donors following a myeloablative conditioning
      regimen were included. Using both CD71 and FSC parameters, we obtained three
      erythroid populations: EryA-C. Ery A (CD71(high) FSC(high)) are basophilic; Ery B
      (CD71(high) FSC(low)) are late basophilic and polychromatic; and Ery C (CD71(low)
      FSC(low)) are orthochromatic erythroblasts and reticulocytes. To analyze the
      effect of transplantation on intramedullary apoptosis, we studied Fas (CD95+) and
      caspase-3 expression in erythroblast subpopulations. RESULTS: All patients
      experienced sustained engraftment, and all surviving patients remained free of
      SCA-related events after transplantation. The erythroid population showed
      expansion in the BM at baseline. After transplant, levels decreased, especially
      of Ery C, in parallel to reduced Fas expression and an initial caspase 3 increase
      in erythroid population, similar to reported later steps of "normal" erythroid
      maturation. CONCLUSIONS: The results suggest a good chance of cure for children
      with SCA, with an excellent survival rate. We also observed "normalization" of
      erythroid populations in parallel with a decreased intramedullary apoptosis rate,
      suggesting normal erythroid maturation in ex-SCA patients after HSCT.

PMID- 25045463
TI  - VUT-MK142 : a new cardiomyogenic small molecule promoting the differentiation of
      pre-cardiac mesoderm into cardiomyocytes.
AB  - Intra-cardiac cell transplantation is a new therapy after myocardial infarction.
      Its success, however, is impeded by the limited capacity of donor cells to
      differentiate into functional cardiomyocytes in the heart. A strategy to overcome
      this problem is the induction of cardiomyogenic function in cells prior to
      transplantation. Among other approaches, recently, synthetic small molecules were
      identified, which promote differentiation of stem cells of various origins into
      cardiac-like cells or cardiomyocytes. The aim of this study was to develop and
      characterise new promising cardiomyogenic synthetic low-molecular weight
      compounds. Therefore, the structure of the known cardiomyogenic molecule
      cardiogenol C was selectively modified, and the effects of the resulting
      compounds were tested on various cell types. From this study, VUT-MK142 was
      identified as the most promising candidate with respect to cardiomyogenic
      activity. Treatment using this novel agent induced the strongest up-regulation of
      expression of the cardiac marker ANF in both P19 embryonic carcinoma cells and
      C2C12 skeletal myoblasts. The activity of VUT-MK142 on this marker superseded
      CgC; moreover, the novel compound significantly up-regulated the expression of
      other cardiac markers, and promoted the development of beating cardiomyocytes
      from cardiovascular progenitor cells. We conclude that VUT-MK142 is a potent new
      cardiomyogenic synthetic agent promoting the differentiation of pre-cardiac
      mesoderm into cardiomyocytes, which may be useful to differentiate stem cells
      into cardiomyocytes for cardiac repair. Additionally, an efficient synthesis of
      VUT-MK142 is reported taking advantage of continuous flow techniques superior to
      classical batch reactions both in yield and reaction time.

PMID- 25045465
TI  - comoR: a software for disease comorbidity risk assessment.
AB  - BACKGROUND: The diagnosis of comorbidities, which refers to the coexistence of
      different acute and chronic diseases, is difficult due to the modern extreme
      specialisation of physicians. We envisage that a software dedicated to
      comorbidity diagnosis could result in an effective aid to the health practice.
      RESULTS: We have developed an R software comoR to compute novel estimators of the
      disease comorbidity associations. Starting from an initial diagnosis, genetic and
      clinical data of a patient the software identifies the risk of disease
      comorbidity. Then it provides a pipeline with different causal inference packages
      (e.g. pcalg, qtlnet etc) to predict the causal relationship of diseases. It also
      provides a pipeline with network regression and survival analysis tools (e.g. Net
      Cox, rbsurv etc) to predict more accurate survival probability of patients. The
      input of this software is the initial diagnosis for a patient and the output
      provides evidences of disease comorbidity mapping. CONCLUSIONS: The functions of
      the comoR offer flexibility for diagnostic applications to predict disease
      comorbidities, and can be easily integrated to high-throughput and clinical data
      analysis pipelines.

PMID- 25045464
TI  - Catalytic Kinetic Resolution of a Dynamic Racemate: Highly Stereoselective beta
      Lactone Formation by N-Heterocyclic Carbene Catalysis.
AB  - This study describes the combined experimental and computational elucidation of
      the mechanism and origins of stereoselectivities in the NHC-catalyzed dynamic
      kinetic resolution (DKR) of alpha-substituted-beta-ketoesters. Density functional
      theory computations reveal that the NHC-catalyzed DKR proceeds by two mechanisms,
      depending on the stereochemistry around the forming bond: 1) a concerted,
      asynchronous formal (2+2) aldol-lactonization process, or 2) a stepwise spiro
      lactonization mechanism where the alkoxide is trapped by the NHC-catalyst. These
      mechanisms contrast significantly from mechanisms found and postulated in other
      related transformations. Conjugative stabilization of the electrophile and non
      classical hydrogen bonds are key in controlling the stereoselectivity. This
      reaction constitutes an interesting class of DKRs in which the catalyst is
      responsible for the kinetic resolution to selectively and irreversibly capture an
      enantiomer of a substrate undergoing rapid racemization with the help of an
      exogenous base.

PMID- 25045516
TI  - Long range Debye-Huckel correction for computation of grid-based electrostatic
      forces between biomacromolecules.
AB  - BACKGROUND: Brownian dynamics (BD) simulations can be used to study very large
      molecular systems, such as models of the intracellular environment, using atomic
      detail structures. Such simulations require strategies to contain the
      computational costs, especially for the computation of interaction forces and
      energies. A common approach is to compute interaction forces between
      macromolecules by precomputing their interaction potentials on three-dimensional
      discretized grids. For long-range interactions, such as electrostatics, grid
      based methods are subject to finite size errors. We describe here the
      implementation of a Debye-Huckel correction to the grid-based electrostatic
      potential used in the SDA BD simulation software that was applied to simulate
      solutions of bovine serum albumin and of hen egg white lysozyme. RESULTS: We
      found that the inclusion of the long-range electrostatic correction increased the
      accuracy of both the protein-protein interaction profiles and the protein
      diffusion coefficients at low ionic strength. CONCLUSIONS: An advantage of this
      method is the low additional computational cost required to treat long-range
      electrostatic interactions in large biomacromolecular systems. Moreover, the
      implementation described here for BD simulations of protein solutions can also be
      applied in implicit solvent molecular dynamics simulations that make use of
      gridded interaction potentials.

PMID- 25045517
TI  - Plasma and Brain Pharmacokinetics of Previously Unexplored Lithium Salts.
AB  - Despite its narrow therapeutic window, lithium is still regarded as the gold
      standard comparator and benchmark treatment for mania. Recent attempts to find
      new drugs with similar therapeutic activities have yielded new chemical entities.
      However, these potential new drugs have yet to match the many bioactivities
      attributable to lithium's efficacy for the treatment of neuropsychiatric
      diseases. Consequently, an intense effort for re-engineering lithium therapeutics
      using crystal engineering is currently underway. We sought to improve the
      likelihood of success of these endeavors by evaluating the pharmacokinetics of
      previously unexplored lithium salts with organic anions (lithium salicylate and
      lithium lactate). We report that these lithium salts exhibit profoundly different
      pharmacokinetics compared to the more common FDA approved salt, lithium
      carbonate, in rats. Remarkably, lithium salicylate produced elevated plasma and
      brain levels of lithium beyond 48 hours post-dose without the sharp peak that
      contributes to the toxicity problems of current lithium therapeutics. These
      findings could be important for the development of the next generation of lithium
      therapeutics.

PMID- 25045518
TI  - Tuning Surface Microstructure and Gradient Property of Polymer by
      Photopolymerizable Polysiloxane-modified Nanogels.
AB  - This paper reports a series of photopolymerizable polysiloxane-modified nanogels
      for regulating surface microstructure and gradient property of polymers, which
      were synthesized by solution polymerization under different feed ratios of a
      methacrylate-modified polysiloxane, urethane dimethacrylate (UDMA) and isobornyl
      methacrylate (IBMA) in the presence of a thiol chain transfer agent. The nanogel
      structure and composition were characterized by proton nuclear magnetic resonance
      (1H-NMR), Fourier transform-infrared spectroscopy (FT-IR), transmission electron
      microscope (TEM), gel permeation chromatography (GPC) and differential scanning
      calorimetry (DSC). The dispersion of these nanogels in triethylene glycol
      dimethacrylate (TEGDMA) can reduce the onset and magnitude of shrinkage stress
      during polymerization without compromise to mechanical properties of the
      resulting polymers. Most importantly, as demonstrated by elemental analysis and X
      ray photoelectron spectroscopy (XPS), the nanogels exhibit good self-floating
      ability in the monomer/polymer matrix and the increase of polysiloxane content in
      the nanogel can enhance the self-floating capability due to the lower surface
      tension and energy associated with the polysiloxane component. As a result, the
      polysiloxane-modified nanogels can spontaneously form a concentration gradient
      that can be locked in upon photopolymerization leading to a well-controlled
      heterogeneous polymer that presents a gradient change in thermal stability. With
      the increase of polysiloxane content, the thermal stability of the polymer was
      improved significantly. Furthermore, the enrichment of the nanogel on the surface
      resulting from the good self-floating ability can reduce the dispersion surface
      energy of gradient polymer film and generate a more hydrophobic surface with
      altered surface microstructure. These photopolymerizable polysiloxane-modified
      nanogels are demonstrated to have potential broad application in the preparation
      of gradient polymer with controlled surface properties.

PMID- 25045519
TI  - Digital Drug Delivery: On-Off Ultrasound Controlled Antibiotic Release from
      Coated Matrices with Negligible Background Leaching.
AB  - Hydrogels, such as crosslinked poly(2-hydroxyethyl methacrylate) (pHEMA) have
      been used extensively in controlled release drug delivery systems. Our previous
      work demonstrated an ultrasound (US)-responsive system based on pHEMA coated with
      a self-assembled multilayer of C12-C18 methylene chains. The resulting coating
      was predominantly crystalline and relatively impermeable, forming an US-activated
      switch that controlled drug release on-demand, and kept the drug within the
      matrix in the absence of US. The device, as developed did, however, show a low
      background drug-leaching rate independent of US irradiation. For some
      applications, it is desirable to have very low or zero background release rates.
      This was achieved here by a combination of new processing steps, and by
      copolymerizing HEMA with a relatively hydrophobic monomer, hydroxypropyl
      methacrylate (HPMA). These advances produced systems with undetectable
      ciprofloxacin background release rates that are capable of US-facilitated drug
      release - up to 14-fold increases relative to controls both before and after US
      exposure. In addition, these observations are consistent with the hypothesis that
      US-mediated disorganization of the coating allows a transient flux of water into
      the matrix where its interaction with bound and dissolved drug facilitates its
      movement both within and out of the matrix.

PMID- 25045520
TI  - Metabolizable energy, nitrogen balance, and ileal digestibility of amino acids in
      quality protein maize for pigs.
AB  - BACKGROUND: To compare the nutritional value and digestibility of five quality
      protein maize (QPM) hybrids to that of white and yellow maize, two experiments
      were carried out in growing pigs. In experiment 1, the energy metabolizability
      and the nitrogen balance of growing pigs fed one of five QPM hybrid diets were
      compared against those of pigs fed white or yellow maize. In experiment 2, the
      apparent and standardized ileal digestibility (AID and SID, respectively) of
      proteins and amino acids from the five QPM hybrids were compared against those
      obtained from pigs fed white and yellow maize. In both experiments, the
      comparisons were conducted using contrasts. RESULTS: The dry matter and nitrogen
      intakes were higher in the pigs fed the QPM hybrids (P < 0.05) than in the pigs
      fed white or yellow maize. Energy digestibility (P < 0.001) and metabolizability
      (P < 0.01) were higher in the pigs fed the white and yellow maize diets than in
      those fed the QPM diets. The AID of lysine was higher (P < 0.01) in the QPM diets
      than in the white and yellow maize. The AIDs of leucine, isoleucine, valine,
      phenylalanine, and methionine were lower in the QPM diets than those of maize
      (white and yellow) (all P < 0.05). Maize (white and yellow) had greater SIDs of
      leucine, isoleucine, valine, phenylalanine, glutamic acid, serine, alanine,
      tyrosine, and proline (P < 0.05). CONCLUSIONS: Based on these results, it was
      concluded that QPM had a lower metabolizable energy content and a higher amount
      of digestible lysine than normal maize.

PMID- 25045521
TI  - Novel gemini cationic lipids with carbamate groups for gene delivery.
AB  - To obtain efficient non-viral vectors, a series of Gemini cationic lipids with
      carbamate linkers between headgroups and hydrophobic tails were synthesized. They
      have the hydrocarbon chains of 12, 14, 16 and 18 carbon atoms as tails,
      designated as G12, G14, G16 and G18, respectively. These Gemini cationic lipids
      were prepared into cationic liposomes for the study of the physicochemical
      properties and gene delivery. The DNA-bonding ability of these Gemini cationic
      liposomes was much better than their mono-head counterparts (designated as M12,
      M14, M16 and M18, respectively). In the same series of liposomes, bonding ability
      declined with an increase in tail length. They were tested for their gene
      transferring capabilities in Hep-2 and A549 cells. They showed higher
      transfection efficiency than their mono-head counterparts and were comparable or
      superior in transfection efficiency and cytotoxicity to the commercial liposomes,
      DOTAP and Lipofectamine 2000. Our results convincingly demonstrate that the gene
      transferring capabilities of these cationic lipids depended on hydrocarbon chain
      length. Gene transfection efficiency was maximal at a chain length of 14, as G14
      can silence about 80 % of luciferase in A549 cells. Cell uptake results indicate
      that Gemini lipid delivery systems could be internalised by cells very
      efficiently. Thus, the Gemini cationic lipids could be used as synthetic non
      viral gene delivery carriers for further study.

PMID- 25045522
TI  - Burkitt's lymphoma presenting with hypopituitarism: a case report and review of
      literature.
AB  - Hypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of
      this report is to present a case of BL presenting with panhypopituitarism and to
      review other case reports of lymphoma presenting with pituitary dysfunction to
      highlight the distinguishing features of these cases from other benign
      aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas.
      We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction
      published from 1998 to 2013 including the present case. The demographics,
      clinical presentations, laboratory features, radiological findings, histological
      diagnosis, treatment administered and outcomes were described. Of the total
      number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while
      27.3% had BL. Anterior pituitary dysfunction was more common than posterior
      pituitary dysfunction at presentation. The other common associated presenting
      symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional
      symptoms. Hypothalamic-pituitary abnormalities were often demonstrated
      radiologically to be associated with cavernous sinus and/or stalk involvement.
      All patients who completed immunochemotherapy responded haematologically.
      Pituitary dysfunction also improved in most cases although the recovery tended to
      be partial. In conclusion, a high index of suspicion of underlying malignancy,
      such as lymphoma, should be present in patients presenting with acute pituitary
      dysfunction associated with painful ophthalmoplegia, rapidly evolving
      neurological features, radiological features atypical of a pituitary adenoma and
      constitutional symptoms. An early diagnosis is essential as prompt initiation of
      definitive therapy will induce disease remission and recovery of pituitary
      dysfunction. LEARNING POINTS: Hypopituitarism may be the presenting symptom of
      lymphoma in the absence of associated overt symptoms or signs of a haematological
      malignancy resulting in delay in diagnosis and institution of treatment.Pituitary
      dysfunction due to tumour infiltration has a greater tendency to involve the
      posterior pituitary and infundibulum resulting in diabetes insipidus and
      hyperprolactinaemia compared with a non-functioning pituitary adenoma.The common
      associated symptoms of hypopituitarism due to lymphoma infiltration of the
      hypothalamic-pituitary system include painful ophthalmoplegia, cranial nerve
      palsies and constitutional symptoms.Radiological abnormalities of the
      hypothalamic-pituitary region are usually present and often associated with
      cavernous sinus or stalk involvement.With early institution of definitive
      treatment, both haematological response and improvement of pituitary dysfunction
      are expected although the reversal of hypopituitarism tends to be partial and
      delayed.A high index of suspicion of underlying malignancy such as lymphoma
      should be present in patients presenting with acute pituitary dysfunction
      associated with painful ophthalmoplegia, radiological features atypical of
      pituitary adenomas and constitutional symptoms to enable early diagnosis and
      prompt initiation of definitive therapy.

PMID- 25045523
TI  - Recurrent pancreatitis in a patient with familial hypocalciuric hypercalcaemia
      treated successfully with cinacalcet.
AB  - A 22-year-old female student presented with a history of recurrent pancreatitis.
      The commonest causes of pancreatitis, including drugs, gallstones,
      corticosteroids, excess alcohol and hypertriglyceridaemia, were excluded. She was
      found to have an elevated serum calcium level that was considered to be the cause
      of her pancreatitis, with a detectable serum parathyroid hormone (PTH). An
      initial diagnosis of primary hyperparathyroidism was made. However, two neck
      explorations failed to reveal a parathyroid adenoma. She was referred to our unit
      three years later as her episodes of pancreatitis were becoming more frequent and
      her calcium level remained persistently elevated. Her investigations were as
      follows: elevated adjusted calcium level of 2.79 mmol/l (2.2-2.58), PTH level of
      4.2 pmol/l (0.6-6.0), low 24 h urine calcium of 0.3 mmol/l and a urine
      calcium:creatinine ratio of <0.003. A clinical diagnosis of familial
      hypocalciuric hypercalcaemia (FHH) was made and confirmed on genetic testing that
      showed a c.1703 G>A mutation in the calcium-sensing receptor gene. Although the
      hypercalcaemia of FHH is usually without sequelae due to the generalised changes
      in calcium sensing, in the presence of this complication she was started on
      cinacalcet 30 mg daily. She had one further episode of pancreatitis with calcium
      levels ranging between 2.53 and 2.66 mmol/l. Her cinacalcet was gradually
      increased to 30 mg three times daily, maintaining her calcium levels in the range
      of 2.15-2.20 mmol/l. She has not had a further episode of pancreatitis for more
      than 2 years. FHH is usually a benign condition with minimal complications from
      hypercalcaemia. Pancreatitis has been reported rarely, and no clear management
      strategy has been defined in these cases. Cinacalcet was successfully used in
      treating recurrent pancreatitis in a patient with FHH by maintaining calcium
      levels in the lower part of the reference range. Whether or not this is an
      effective long-term treatment remains yet to be seen. LEARNING POINTS: FHH is an
      important differential diagnosis for hypercalcaemia.FHH can rarely cause
      pancreatitis.No clear strategy is available to help in the management of patients
      with pancreatitis due to FHH.Cinacalcet was effective in lowering serum calcium
      levels and reducing the frequency of pancreatitis in our patient with FHH.

PMID- 25045525
TI  - Adsorption performance of packed bed column for nitrate removal using PAN-oxime
      nano Fe2O3.
AB  - A continuous fixed bed study was carried out by using PAN-oxime-nano Fe2O3 as a
      sorbent for the removal of nitrate from aqueous solution. The effect of factors,
      such as flow rate (2, 5 and 7 mL/min) and bed depth (5, 10 and 15 cm) were
      studied. Data confirmed that the breakthrough curves were dependent on flow rate
      and bed depth. The adsoption capacities observed in diffent conditions of flow
      rates (2,5 and 7 mL/min) were 11.65, 24.38 and 25.89, respectively. Thomas model
      was applied to experimental data to predict the breakthrough curves using linear
      regression and to determine the characteristic parameters of the packed bed
      column. Bed depth/service time analysis (BDST) model was used to investigate the
      effect of bed depth on breakthrough curves. The results showed that Thomas model
      was suitable for the normal description of breakthrough curve at the experimental
      condition. The data were in good agreement with BDST model with R(2) > 0.98.
      Statistical analyses were performed on fluoride removal obtained from different
      flow rates using SPSS16 software by applying Kruskal- Wallis test. These findings
      suggested that PAN-oxime-nano Fe2O3 in the column structure presents a great
      potential in removal of nitrate from aqueous solutions. 

PMID- 25045524
TI  - Gender differences in myocardial function and arterio-ventricular coupling in
      response to maximal exercise in adolescent floor-ball players.
AB  - BACKGROUND: The hemodynamic and cardiac responses to exercise have been widely
      investigated in adults. However, little is known regarding myocardial performance
      in response to a short bout of maximal exercise in adolescents. We therefore
      sought to study alterations in myocardial function and investigate sex-influences
      in young athletes after maximal cardiopulmonary testing. METHODS: 51 adolescent
      (13-19 years old) floor-ball players (24 females) were recruited. All subjects
      underwent a maximal exercise test to determine maximal oxygen uptake (VO2max) and
      cardiac output. Cardiac performance was investigated using conventional and
      tissue velocity imaging, as well as 2D strain echocardiography before and 30
      minutes following exercise. Arterio-ventricular coupling was evaluated by means
      of single beat ventricular elastance and arterial elastance. RESULTS: Compared to
      baseline the early diastolic myocardial velocity (E'LV) at the basal left
      ventricular (LV) segments declined significantly (females: E'LV: 14.7 +/- 2.6 to
      13.6 +/- 2.9 cm/s; males: 15.2 +/- 2.2 to 13.9 +/- 2.3 cm/s, p < 0.001 for both).
      Similarly, 2D strain decreased significantly following exercise (2D strain LV:
      from 21.5 +/- 2.4 to 20.2 +/- 2.7% in females, and from 20 +/- 1 to 17.9 +/- 1.5%
      in males, p < 0.05 for both). However, there were no significant changes in LV
      contractility estimated by elastance in either sex following exercise (p > 0.05).
      Arterial elastance) Ea) at baseline was identified as the only predictor of
      VO2max in males (r = 0.76, p < 0.001) but not in females (p > 0.05). CONCLUSIONS:
      The present study demonstrates that vigorous exercise of short duration results
      in a significant decrease of longitudinal myocardial motion in both sexes.
      However, in view of unaltered end systolic LV elastance (Ees), these reductions
      most probably reflect changes in the loading conditions and not an attenuation of
      myocardial function per se. Importantly, we show that arterial load at rest acts
      as a strong predictor of VO2max in males but not in female subjects.

PMID- 25045526
TI  - Imaging assessment of a portable hemodialysis device: detection of possible
      failure modes and monitoring of functional performance.
AB  - BACKGROUND: The purpose of this study was to investigate the utility and
      limitations of various imaging modalities in the noninvasive assessment of a
      novel compact hemodialyzer under development for renal replacement therapy, with
      specific aim towards monitoring its functional performance. METHODS: The
      prototype is a 4*3*6 cm aluminum cartridge housing "blood" and "dialysate" flow
      paths arranged in parallel. A sheet of semipermeable silicon nanopore membranes
      forms the blood-dialysate interface, allowing passage of small molecules. Blood
      flow was simulated using a peristaltic pump to instill iodinated contrast through
      the blood compartment, while de-ionized water was instilled through the dialysate
      compartment at a matched rate in the countercurrent direction. Images were
      acquired under these flow conditions using multi-detector computed tomography
      (MDCT), fluoroscopy, high-resolution quantitative computed tomography (HR-QCT),
      and magnetic resonance imaging (MRI). MDCT was used to monitor contrast diffusion
      efficiency by plotting contrast density as a function of position along the path
      of flow through the cartridge during steady state infusion at 1 and 20 mL/min.
      Both linear and exponential regressions were used to model contrast decay along
      the flow path. RESULTS: Both linear and exponential models of contrast decay
      appeared to be reasonable approximations, yielding similar results for contrast
      diffusion during a single pass through the cartridge. There was no measurable
      difference in contrast diffusion when comparing 1 mL/min and 20 mL/min flow
      rates. Fluoroscopy allowed a gross qualitative assessment of flow within the
      device, and revealed flow inhomogeneity within the corner of the cartridge
      opposite the blood inlet port. MRI and HR-QCT were both severely limited due to
      the paramagnetic properties and high atomic number of the target material,
      respectively. During testing, we encountered several causes of device
      malfunction, including leak formation, trapped gas, and contrast-mediated
      nanopore clogging. We illustrate the imaging manifestations of each. CONCLUSIONS:
      Despite the inherent challenges in imaging a predominantly metallic device, some
      modalities show potential in the non-invasive assessment of a novel compact
      hemodialyzer. The approaches described here could potentially be translated to
      device evaluation in the implanted setting.

PMID- 25045527
TI  - Recruitment and retention of human autologous CD34+ CD117+ CD133+ bone marrow
      stem cells to infarcted myocardium followed by directed vasculogenesis: Novel
      strategy for cardiac regeneration.
AB  - BACKGROUND: Ongoing clinical trials, in regenerative therapy of patients
      suffering from myocardial infarctions, rely primarily upon administration of bone
      marrow stem cells to the infarcted zones. Unfortunately, low retention of these
      cells, to the therapeutic delivery sites, reduces effectiveness of this strategy;
      thus it has been identified as the most critical problem for advancement of
      cardiac regenerative medicine. SPECIFIC AIMS: The specific aim of this work was
      three-fold: (1) to isolate highly viable populations of human, autologous CD34+,
      CD117+, and CD133+ bone marrow stem cells; (2) to bioengineer heterospecific,
      tetravalent antibodies and to use them for recruiting of the stem cells to
      regenerated zones of infarcted myocardium; (3) to direct vasculogenesis of the
      retained stem cells with the defined factors. PATIENTS METHODS: Cardiac tissue
      was biopsied from the hearts of the patients, who were receiving orthotopic heart
      transplants after multiple cardiac infarctions. This tissue was used to engineer
      fully human in vitro models of infarcted myocardium. Bone marrow was acquired
      from these patients. The marrow cells were sorted into populations of cells
      displaying CD34, CD117, and CD133. Heterospecific, tetravalent antibodies were
      bioengineered to bridge CD34, CD117, CD133 displayed on the stem cells with
      cardiac myosin of the infarcted myocardium. The sorted stem cells were
      administered to the infarcted myocardium in the in vitro models. RESULTS:
      Administration of the bioengineered, heterospecific antibodies preceding
      administration of the stem cells greatly improved the stem cells' recruitment and
      retention to the infarcted myocardium. Treatment of the retained stem cells with
      vascular endothelial growth factor and angiopoietin efficiently directed their
      differentiation into endothelial cells, which expressed vascular endothelial
      cadherin, platelet / endothelial cell adhesion molecule, claudin, and occludin,
      while forming tight and adherens junctions. CONCLUSIONS: This novel strategy
      improved retention of the patients' autologous bone marrow stem cells to the
      infarcted myocardium followed by directed vasculogenesis. Therefore, it is worth
      pursuing it in support of the ongoing clinical trials of cardiac regenerative
      therapy.

PMID- 25045528
TI  - Risk-stratified cardiovascular screening including angiographic and procedural
      outcomes of percutaneous coronary interventions in renal transplant candidates.
AB  - Background. Benefits of cardiac screening in kidney transplant candidates (KTC)
      will be dependent on the availability of effective interventions. We
      retrospectively evaluated characteristics and outcome of percutaneous coronary
      interventions (PCI) in KTC selected for revascularization by a cardiac screening
      approach. Methods. In 267 patients evaluated 2003 to 2006, screening tests
      performed were reviewed and PCI characteristics correlated with major adverse
      cardiovascular events (MACE) during a follow-up of 55 months. Results. Stress
      tests in 154 patients showed ischemia in 28 patients (89% high risk). Of 58
      patients with coronary angiography, 38 had significant stenoses and 18 cardiac
      interventions (6.7% of all). 29 coronary lesions in 17/18 patients were treated
      by PCI. Angiographic success rate was 93.1%, but procedural success rate was only
      86.2%. Long lesions (P = 0.029) and diffuse disease (P = 0.043) were associated
      with MACE. In high risk patients, cardiac screening did not improve outcome as
      21.7% of patients with versus 15.5% of patients without properly performed
      cardiac screening had MACE (P = 0.319). Conclusion. The moderate procedural
      success of PCI and poor outcome in long and diffuse coronary lesions underscore
      the need to define appropriate revascularization strategies in KTC, which will be
      a prerequisite for cardiac screening to improve outcome in these high-risk
      patients. 

PMID- 25045529
TI  - The influence of prior hyperthyroidism on euthyroid graves' ophthalmopathy.
AB  - Background. To investigate the influence of previous exposure to elevated thyroid
      hormones in euthyroid Graves' ophthalmopathy. Design. Retrospective,
      observational case series in university setting Median follow-up of 1 year with
      ranges of 0,8-7,6 years. Study performance of 10 years. Participants. We reviewed
      the clinical records of 731 Graves' ophthalmopathy patients. There were 88 (12%)
      patients with onset of Graves' ophthalmopathy during euthyroidism: 37 (5%)
      patients had ophthalmopathy without known history of thyroid dysfunction (group
      A) and 51 patients (6%) had onset of ophthalmopathy 6 months or more euthyroid
      after completion of antithyroid therapy (group B). Main Outcome Measures. Graves'
      ophthalmopathy was graded using the EUGOGO severity criteria. Unilaterality was
      investigated. TSH receptor antibody and thyroid peroxidase antibody were measured
      as markers of Graves' disease. Results. Group A had more often a normal ocular
      motility (46%) and less proptosis (14 +/- 4 mm) compared to group B (22%, 16 +/-
      4 mm) (P = 0.032 and 0.028, resp.). TSH receptor antibody was more frequently
      elevated in group B (94%) than in group A (17%) (P < 0.001). Conclusion. Patients
      with euthyroid Graves' ophthalmopathy present more often with ocular muscle
      restriction and proptosis when previously exposed to elevated thyroid hormones. 

PMID- 25045530
TI  - Studies of inhibitory mechanisms of propeptide-like cysteine protease inhibitors.
AB  - Mouse cytotoxic T-lymphocyte antigen-2alpha (CTLA-2alpha), Drosophila CTLA-2-like
      protein (crammer), and Bombyx cysteine protease inhibitor (BCPI) belong to a
      novel family of cysteine protease inhibitors (I29). Their inhibitory mechanisms
      were studied comparatively. CTLA-2alpha contains a cysteine residue (C75), which
      is essential for its inhibitory potency. The CTLA-2alpha monomer was converted to
      a disulfide-bonded dimer in vitro and in vivo. The dimer was fully inhibitory,
      but the monomer, which possessed a free thiol residue, was not. A disulfide
      bonded CTLA-2alpha/cathepsin L complex was isolated, and a cathepsin L subunit
      with a molecular weight of 24,000 was identified as the interactive enzyme
      protein. Crammer also contains a cysteine residue (C72). Both dimeric and
      monomeric forms of crammer were inhibitory. A crammer mutant with Cys72 to
      alanine (C72A) was fully inhibitory, while the replacement of Gly73 with alanine
      (G73A) caused a significant loss in inhibitory potency, which suggests a
      different inhibition mechanism from CTLA-2alpha. BCPI does not contain cysteine
      residue. C-terminal region (L77-R80) of BCPI was essential for its inhibitory
      potency. CTLA-2alpha was inhibitory in the acidic pH condition but stabilized
      cathepsin L under neutral pH conditions. The different inhibition mechanisms and
      functional considerations of these inhibitors are discussed. 

PMID- 25045532
TI  - Perception of childhood obesity and support for prevention policies among Latinos
      and Whites.
AB  - A cross-sectional survey was administered to Latino and White residents of Omaha,
      NE, to assess perception of the childhood obesity problem, attribution of
      responsibility, and support for obesity-related policies. The sample included
      40.8% (n = 271) Latinos and 59.2% (n = 393) Whites. Among Latinos, 25% did not
      see childhood obesity as a problem, compared to 6% of Whites (P < 0.001). This
      difference persisted after adjusting for age, gender, and education level (odds
      ratio (OR) 2.10, 95% confidence interval (CI) 1.07-4.14). Latinos were more
      likely to agree that government was responsible for addressing childhood obesity
      compared to Whites (OR 2.81, 95% CI 1.82-4.35). Higher support for policy
      interventions was observed among individuals who perceived childhood obesity as a
      big problem compared to those who did not, independent of race, sex, age, or
      education level. The relationship between support for tax-based policies and
      perception of the childhood obesity problem was mainly evident among Latinos
      rather than Whites. Despite city-wide efforts to address obesity, differential
      penetration in community subgroups appears evident. There is room to further
      engage Latinos in the cause of obesity. Deepening community awareness about the
      consequences and complexity of childhood obesity can lead to stronger support for
      childhood obesity policy interventions.

PMID- 25045531
TI  - Neuroantibody biomarkers: links and challenges in environmental neurodegeneration
      and autoimmunity.
AB  - The majority of neurodegenerative (ND) and autoimmune diseases (AID) remain
      idiopathic. The contribution of environmental chemicals to the development of
      these disorders has become of great interest in recent years. A convergence of
      mechanism between of ND and AID development has also emerged. In the case of ND,
      including neurotoxicity, the focus of this review, work over the last two decade
      in the realm of biomarker development, indicates that the immune response
      provides a venue whereby humoral immunity, in the form of autoantibodies to
      nervous system specific proteins, or neuroantibodies (NAb), may provide, once
      validated, a sensitive high throughput surrogate biomarker of effect with the
      potential of predicting outcome in absence of overt
      neurotoxicity/neurodegeneration. In addition, NAb may prove to be a contributor
      to the progression of the nervous system pathology, as well as biomarker of stage
      and therapeutic efficacy. There is a compelling need for biomarkers of effect in
      light of the introduction of new chemicals, such as nanoengineered material,
      where potential neurotoxicity remains to be defined. Furthermore, the convergence
      of mechanisms associated with ND and AID draws attention to the neglected arena
      of angiogenesis in defining the link between environment, ND, and AID. 

PMID- 25045533
TI  - Cost of Care for HIV-Infected Patients with Co-Occurring Substance Use Disorder
      or Psychiatric Disease: Report from a Large, Integrated Health Plan.
AB  - Background. The costs of providing care to HIV-infected (HIV+) patients with co
      occurring diagnoses of substance use (SU) disorder or psychiatric disease (PD)
      are not well documented. It is our objective to evaluate costs in these HIV+
      patients receiving care in a large health plan. Methods. We conducted a
      retrospective cohort study from 1995 to 2010 to compare costs of healthcare in
      HIV+ patients with and without co-occurring SU disorder and/or PD diagnoses.
      Estimates of proportional differences in costs (rate ratios) were obtained from
      repeated measures generalized linear regression. Models were stratified by cost
      category (e.g., inpatient, outpatient). Results. Mean total healthcare costs per
      patient per year were higher in HIV+ patients diagnosed with SU disorder or PD
      compared to HIV+ patients without these comorbid conditions. After controlling
      for confounders, total mean costs remained significantly higher in patients
      diagnosed with SU disorder (RR = 1.24, 95% CI = 1.18-1.31) or PD (RR = 1.19, 95%
      CI = 1.15-1.24). Mean outpatient care costs were significantly greater in
      patients with both SU disorder and PD (RR = 1.52, 95% CI = 1.41-1.64).
      Conclusions. Given these higher expenditures in the care of HIV+ patients with
      comorbid SU disorder and/or PD, greater efforts to facilitate SU disorder or PD
      treatment initiation and persistence could provide substantial savings. 

PMID- 25045534
TI  - Prognostic factors and survival in patients treated surgically for recurrent
      metastatic uterine leiomyosarcoma.
AB  - BACKGROUND: Uterine leiomyosarcoma (LMS) is a rare diagnosis, which is seldom
      cured when it recurs with metastatic disease. We evaluated patients who present
      with first time recurrence treated surgically to determine prognostic factors
      associated with long-term survival. METHODS: Over a 16-year period, 41 patients
      were operated on for recurrent uterine sarcoma. Data examined included patient
      age, date of initial diagnosis, tumor histology, grade at the initial diagnosis,
      cytopathology changes in tumor activity from the initial diagnosis, residual
      tumor after all operations, use of adjuvant therapy, dates and sites of all
      recurrences, and disease status at last followup. RESULTS: 24 patients were
      operated for first recurrence of metastatic uterine LMS. Complete tumor resection
      with histologic negative margins was achieved in 16 (67%) patients. Overall
      survival was significantly affected by the FIGO stage at the time of the initial
      diagnosis, the ability to obtain complete tumor resection at the time of surgery
      for first time recurrent disease, single tumor recurrence, and recurrence greater
      than 12 months from the time of the initial diagnosis. Median disease-free
      survival was 14 months and overall survival was 27 months. CONCLUSION: Our
      findings suggest that stage 1 at the time of initial diagnosis, recurrence
      greater than 12 months, isolated tumor recurrence, and the ability to remove
      ability to perform complete tumor resection at the time of the first recurrence
      can afford improved survival in selected patientsat the time of the first
      recurrence can afford improved survival in selected patients.

PMID- 25045535
TI  - Evaluating the linguistic appropriateness and cultural sensitivity of a self
      report system for spanish-speaking patients with cancer.
AB  - Spanish speakers in the United States encounter numerous communication barriers
      during cancer treatment. Communication-focused interventions may help Spanish
      speakers communicate better with healthcare providers and manage symptoms and
      quality of life issues (SQOL). For this study, we developed a Spanish version of
      the electronic self-report assessment for cancer (ESRA-C), a web-based program
      that helps people with cancer report, track, and manage cancer-related SQOL. Four
      methods were used to evaluate the Spanish version. Focus groups and cognitive
      interviews were conducted with 51 Spanish-speaking individuals to elicit
      feedback. Readability was assessed using the Fry readability formula. The
      cultural sensitivity assessment tool was applied by three bilingual, bicultural
      reviewers. Revisions were made to personalize the introduction using a patient
      story and photos and to simplify language. Focus group participants endorsed
      changes to the program in a second round of focus groups. Cultural sensitivity of
      the program was scored unacceptable ([Formula: see text]) for audiovisual
      material and acceptable ([Formula: see text]) for written material. Fry reading
      levels ranged from 4th to 10th grade. Findings from this study provide several
      next steps to refine ESRA-C for Spanish speakers with cancer. 

PMID- 25045537
TI  - Relational coordination and organisational social capital association with
      characteristics of general practice.
AB  - Background. Relational coordination (RC) and organisational social capital (OSC)
      are measures of novel aspects of an organisation's performance, which have not
      previously been analysed together, in general practice. Objectives. The aim of
      this study was to analyse the associations between RC and OSC, and
      characteristics of general practice. Methods. Questionnaire survey study
      comprising 2074 practices in Denmark. Results. General practitioners (GPs) rated
      both RC and OSC in their general practice higher than their secretaries and
      nurses. The practice form was statistically significantly associated with high RC
      and OSC. RC was positively associated with the number of patients listed with a
      practice per staff, where staff is defined as all members of a practice including
      both owners and employees. Conclusion. The study showed that RC and OSC were
      significantly associated with type of profession and practice type. RC was also
      found to be significantly positively associated with number of patients per
      staff. However, the low response rate must be taken into consideration when
      interpreting the self-reported results of this study. 

PMID- 25045536
TI  - Computer vision tools for low-cost and noninvasive measurement of autism-related
      behaviors in infants.
AB  - The early detection of developmental disorders is key to child outcome, allowing
      interventions to be initiated which promote development and improve prognosis.
      Research on autism spectrum disorder (ASD) suggests that behavioral signs can be
      observed late in the first year of life. Many of these studies involve extensive
      frame-by-frame video observation and analysis of a child's natural behavior.
      Although nonintrusive, these methods are extremely time-intensive and require a
      high level of observer training; thus, they are burdensome for clinical and large
      population research purposes. This work is a first milestone in a long-term
      project on non-invasive early observation of children in order to aid in risk
      detection and research of neurodevelopmental disorders. We focus on providing low
      cost computer vision tools to measure and identify ASD behavioral signs based on
      components of the Autism Observation Scale for Infants (AOSI). In particular, we
      develop algorithms to measure responses to general ASD risk assessment tasks and
      activities outlined by the AOSI which assess visual attention by tracking facial
      features. We show results, including comparisons with expert and nonexpert
      clinicians, which demonstrate that the proposed computer vision tools can capture
      critical behavioral observations and potentially augment the clinician's
      behavioral observations obtained from real in-clinic assessments. 

PMID- 25045538
TI  - Deliberate self-poisoning presenting to an emergency medicine network in South
      East melbourne: a descriptive study.
AB  - Background. Deliberate self-poisoning (DSP) comprises a small but significant
      proportion of presentations to the emergency department (ED). However, the
      prevalence and patient characteristics of self-poisoning attendances to EDs in
      Victoria have not been recently characterised. Aim. To identify and compare the
      characteristics of adult patients presenting to the three EDs of Monash Health
      following DSP. Methods. Retrospective clinical audit of adult DSP attendances
      between 1st July 2009 and 30th June 2012. Results. A total of 3558 cases over
      three years were identified fulfilling the search criteria. The mean age of
      patients was 36.3 years with the largest numbers aged between 18 and 30 (38%).
      About 30% of patients were born overseas. Forty-eight percent were discharged
      home, 15% were admitted to ED short stay units, and 5% required ICU admission.
      The median ED length of stay was 359 minutes (IQR 231-607). The most frequently
      reported substances in DSP were benzodiazepines (36.6%), paracetamol (22.2%), and
      antipsychotics (12.1%). Exposure to more than one substance for the episode of
      DSP was common (47%). Conclusion. This information may help identify the trends
      in poisoning substances used for DSP in Victoria, which in turn may provide
      clinicians with information to provide more focused and targeted interventions. 

PMID- 25045539
TI  - Prognostic value of melanoma inhibitory activity protein in localized cutaneous
      malignant melanoma.
AB  - Background. Cutaneous malignant melanoma (CMM) is a heterogeneous disease,
      acknowledged for its lack of predictability regarding clinical evolution. In
      order to appreciate a patient's individual prognosis, an attempt is made to find
      new tumor markers that parallel the disease progression. Objective. To identify
      if melanoma inhibitory activity (MIA) protein could represent a tool for
      selecting high risk early stages melanoma patients. Method. Between 2008 and
      2013, 155 patients with CMM were treated in our clinic. 84 of them were
      classified into stages I and II, according to TNM 2009. MIA serum concentration
      was measured in all patients and 50 healthy donors. A cut-off value of 9.4 ng/ml
      was established using the ROC curve. Results. All patients were followed up by
      periodic investigations every 6 months. We have noticed that 66% of patients with
      MIA serum values at diagnosis greater than 9.4 ng/mL have relapsed, while only 5%
      of patients with MIA serum concentration below the estimated threshold, recurred
      during the follow-up period (P = 0.000). The death risk was 12 times higher in
      pathological MIA group of patients (P = 0.0001). Conclusions. Our data suggest
      that MIA is an independent prognostic factor for patients with localized CMM. 

PMID- 25045540
TI  - Tailor-made pentablock copolymer based formulation for sustained ocular delivery
      of protein therapeutics.
AB  - The objective of this research article is to report the synthesis and evaluation
      of novel pentablock copolymers for controlled delivery of macromolecules in the
      treatment of posterior segment diseases. Novel biodegradable PB copolymers were
      synthesized by sequential ring-opening polymerization. Various ratios and
      molecular weights of each block (polyglycolic acid, polyethylene glycol,
      polylactic acid, and polycaprolactone) were selected for synthesis and to
      optimize release profile of FITC-BSA, IgG, and bevacizumab from nanoparticles
      (NPs) and thermosensitive gel. NPs were characterized for particle size,
      polydispersity, entrapment efficiency, and drug loading. In vitro release study
      of proteins from NPs alone and composite formulation (NPs suspended in
      thermosensitive gel) was performed. Composite formulations demonstrated no or
      negligible burst release with continuous near zero-order release in contrast to
      NPs alone. Hydrodynamic diameter of protein therapeutics and hydrophobicity of PB
      copolymer exhibited significant effect on entrapment efficiency and in vitro
      release profile. CD spectroscopy confirmed retention of structural conformation
      of released protein. Biological activity of released bevacizumab was confirmed by
      in vitro cell proliferation and cell migration assays. It can be concluded that
      novel PB polymers can serve a platform for sustained delivery of therapeutic
      proteins. 

PMID- 25045541
TI  - Single high intensity focused ultrasound session as a whole gland primary
      treatment for clinically localized prostate cancer: 10-year outcomes.
AB  - Objectives. To assess the treatment outcomes of a single session of whole gland
      high intensity focused ultrasound (HIFU) for patients with localized prostate
      cancer (PCa). Methods. Response rates were defined using the Stuttgart and
      Phoenix criteria. Complications were graded according to the Clavien score.
      Results. At a median follow-up of 94months, 48 (44.4%) and 50 (46.3%) patients
      experienced biochemical recurrence for Phoenix and Stuttgart definition,
      respectively. The 5- and 10-year actuarial biochemical recurrence free survival
      rates were 57% and 40%, respectively. The 10-year overall survival rate, cancer
      specific survival rate, and metastasis free survival rate were 72%, 90%, and 70%,
      respectively. Preoperative high risk category, Gleason score, preoperative PSA,
      and postoperative nadir PSA were independent predictors of oncological failure.
      24.5% of patients had self-resolving LUTS, 18.2% had urinary tract infection, and
      18.2% had acute urinary retention. A grade 3b complication occurred in 27
      patients. Pad-free continence rate was 87.9% and the erectile dysfunction rate
      was 30.8%. Conclusion. Single session HIFU can be alternative therapy for
      patients with low risk PCa. Patients with intermediate risk should be informed
      about the need of multiple sessions of HIFU and/or adjuvant treatments and HIFU
      performed very poorly in high risk patients. 

PMID- 25045542
TI  - Environmental Tobacco Smoke Exposure during Intrauterine Period, Promotes Caspase
      Dependent and Independent DNA Fragmentation in Sertoli-Germ Cells.
AB  - Objectives. To investigate the effect of cigarette smoke exposure during
      intrauterine period on neonatal rat testis. Methods. Twenty-five rats were
      randomized to be exposed to cigarette smoke with the Walton Smoking Machine or to
      room air during their pregnancies. The newborn male rats (n = 21) were grouped as
      group 1 (n = 15) which were exposed to cigarette smoke during intrauterine life
      and group 2 (n = 6) which were exposed to room air during intrauterine life. The
      orchiectomy materials were analyzed with TUNEL immunofluorescent staining for
      detection of DNA damage. To detect apoptosis, immunohistochemical analyses with
      caspase-3 were performed. Primary outcomes were apoptotic index and
      immunohistochemical scores (HSCORES); secondary outcomes were Sertoli-cell count
      and birth-weight of rats. Results. Sertoli cell apoptosis was increased in group
      1 (HSCORE = 210.6 +/- 41.9) when compared to group 2 (HSCORE = 100.0 +/- 17.8) (P
      = 0.001). Sertoli cell count was decreased in group 1 (P = 0.043). The HSCORE for
      the germ cells was calculated as 214.0 +/- 46.2 in group 1 and 93.3 +/- 10.3 in
      group 2 (P = 0.001) referring to an increased germ cell apoptosis in group 1. The
      apoptotic indexes for group 1 were 49.6 +/- 9.57 and 29.98 +/- 2.34 for group 2
      (P = 0.001). The immunofluorescent technique demonstrated increased DNA damage in
      seminiferous epithelium in group 1. Conclusions. Intrauterine exposure to
      cigarette smoke adversely affects neonatal testicular structuring and diminishes
      testicular reserve. 

PMID- 25045543
TI  - Antidepressant Effects of Mallotus oppositifolius in Acute Murine Models.
AB  - Objective. Hydroalcoholic extract of leaves of Mallotus oppositifolius (MOE), a
      plant used for CNS conditions in Ghana, was investigated for acute antidepressant
      effects in the forced swimming (FST) and tail suspension tests (TST). Results. In
      both FST and TST, MOE (10, 30, and 100 mg kg(-1)) significantly decreased
      immobility periods and frequencies. A 3-day pretreatment with 200 mg kg(-1),
      i.p., para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor,
      reversed the decline in immobility and the increase of swimming score induced by
      MOE in the modified FST. Pretreatment with reserpine alone (1 mg kg(-1)), alpha 
      methyldopa alone (400 mg kg(-1), i.p.), or a combination of both drugs failed to
      reverse the decline in immobility or the increase in swimming score caused by the
      extract in the modified FST. The extract potentiated the frequency of head twitch
      responses induced by 5-hydroxytryptamine. Pretreatment with d-serine (600 mg kg(
      1), i.p.), glycine/NMDA agonist, abolished the behavioural effects of MOE while d
      cycloserine (2.5 mg kg(-1), i.p.), a glycine/NMDA partial agonist, potentiated it
      in both TST and modified FST. Conclusion. The extract exhibited antidepressant
      effects in mice which is mediated by enhancement of serotoninergic
      neurotransmission and inhibition of glycine/NMDA receptor activation. 

PMID- 25045544
TI  - Amelogenesis imperfecta and screening of mutation in amelogenin gene.
AB  - The aim of this study was to report the clinical findings and the screening of
      mutations of amelogenin gene of a 7-year-old boy with amelogenesis imperfecta
      (AI). The genomic DNA was extracted from saliva of patient and his family,
      followed by PCR and direct DNA sequencing. The c.261C>T mutation was found in
      samples of mother, father, and brother, but the mutation was not found in the
      sequence of the patient. This mutation is a silent mutation and a single
      nucleotide polymorphism (rs2106416). Thus, it is suggested that the mutation
      found was not related to the clinical presence of AI. Further research is
      necessary to examine larger number of patients and genes related to AI. 

PMID- 25045545
TI  - Orthostatic Dysregulation during Postural Change on the Dental Chair and
      Intraoperative Monitoring by Heart Rate Variability Analysis.
AB  - This is the first case report of orthostatic dysregulation (OD) manifested during
      postural change on the dental chair and intraoperatively monitored by heart rate
      variability (HRV) analysis. OD-associated autonomic dysfunction is induced by
      postural changes and easily leads to disturbance in circulatory dynamics;
      however, most dental practices have not yet realized the importance of managing
      OD. We measured autonomic activity in a patient with OD during dental therapy and
      assessed the clinical significance of HRV analysis for OD. The patient was a 17
      year-old Japanese female. She was diagnosed with impacted wisdom teeth and had no
      previous history of a distinct systemic disease. A surgical procedure to extract
      the teeth was safely performed under both local anesthesia and sedation with
      nitrous oxide and midazolam. After the surgery, her postural change to sitting
      induced orthostatic hypotension. HRV variables showed parasympathetic dominance
      due to the upright position. Subsequently, her posture was returned to supine,
      and atropine sulfate administration for the immediate treatment of OD returned
      her blood pressure to normal levels. HRV variables showed relative sympathetic
      dominance due to an atropine-derived parasympathetic blockade. HRV analysis
      revealed OD-associated autonomic dysfunction and should become a standard tool
      for safe and secure dental management of OD. 

PMID- 25045546
TI  - Cleidocranial dysplasia case report: remodeling of teeth as aesthetic restorative
      treatment.
AB  - Cleidocranial dysplasia (CCD), is an autosomal dominant disorder with a
      prevalence of 1 in 1,000,000 individuals. It is generally characterized by
      orofacial manifestations, including enamel hypoplasia, retained primary teeth,
      and impacted permanent and supernumerary teeth. The successful treatment
      involving a timing intervention (orthodontic-maxillofacial surgeons-restorative)
      is already described. However, the restorative treatment might improve the
      aesthetic final result in dentistry management for patients with cleidocranial
      dysplasia. Objective. Therefore, this clinical report presents a conservative
      restorative management (enamel microabrasion, dental bleaching, and direct
      composite resin) for aesthetic solution for a patient with CCD. Clinical
      Considerations. The cosmetic remodeling is a conservative, secure, and low cost
      therapy that can be associated with other procedures such as enamel microabrasion
      and dental bleaching to achieve optimal outcome. Additionally, the Golden
      Proportion can be used to guide dental remodeling to improve the harmony of the
      smile and the facial composition. Conclusions. Thus, dentists must know and be
      able to treat dental aesthetic problems in cleidocranial dysplasia patients. The
      intention of this paper is to describe a restorative approach with the cosmetic
      remodeling teeth (by grinding or addicting material) associated with enamel
      microabrasion and dental bleaching to reestablish the form, shape, and color of
      smile for patients with cleidocranial dysplasia. 

PMID- 25045547
TI  - A rare cause of acute abdomen: an isolated falciform ligament necrosis.
AB  - The falciform ligament is one of the anatomical structures which attach the liver
      to the diaphragm and anterior abdominal wall. Primary falciform ligament is very
      rare. In this article, we present a case of an isolated falciform ligament
      necrosis, a rare primary pathology of the falciform ligament, who was admitted
      with acute abdomen. CASE PRESENTATION: A 64-year-old female patient was admitted
      with the complaints of pain. Laboratory test results showed a leukocyte count of
      17,000/mm(3). Imaging studies demonstrated intra-abdominal reactionary fluid
      along with a heterogeneous mass localized in the falciform ligament. Exploratory
      laparotomy revealed a necrotic mass of the falciform ligament. No other pathology
      responsible for falciform ligament necrosis was found. We believe that falciform
      ligament necrosis should be considered a preliminary diagnosis, if any ligament
      abnormality, tumor, intraligament air density, or the presence of reactionary
      fluid surrounding the ligament is detected through abdominal imaging studies.

PMID- 25045548
TI  - A 23-year-old female with a mixed germ cell tumor of the pituitary infundibulum:
      the challenge of differentiating neoplasm from lymphocytic
      infundibuloneurohypophysitis-a case report and literature review.
AB  - The pathologic spectrum of diseases that infiltrate the pituitary infundibulum
      includes a broad variety of clinical entities. There are significant differences
      in the prevalence of these etiologies depending on the age of presentation.
      Lymphocytic infundibuloneurohypophysitis (LINH) predominates over other causes of
      infundibular disease in adults over age 21. Differentiating LINH from other
      causes of infundibular disease can be difficult because the various etiologies
      often have similar clinical presentations and radiologic imaging characteristics.
      We report the first case in an adult of a mixed germ cell tumor comprised of
      germinoma and embryonal cell carcinoma infiltrating the pituitary infundibulum.
      In our case, a 23-year-old female was initially misdiagnosed as having LINH. She
      presented with panhypopituitarism and diabetes insipidus, which is the most
      common initial presentation in both entities. The two diagnoses are difficult to
      distinguish based on MRI imaging, CSF findings, and histopathological
      examination. Our case demonstrates the need for close follow-up of patients with
      isolated lesions of the pituitary infundibulum and reinforces the need for biopsy
      of an infundibular lesion when progression of disease is demonstrated. In our
      case, biopsy with comprehensive immunohistochemical staining was the sole means
      of making a definitive diagnosis. 

PMID- 25045549
TI  - Ovarian leydig cell hyperplasia: an unusual case of virilization in a
      postmenopausal woman.
AB  - Objective. To report an unusual case of ovarian Leydig cell hyperplasia resulting
      in virilization in a postmenopausal woman. Methods. Patient's medical history and
      pertinent literature were reviewed. Results. A 64-year-old woman presented with
      virilization with worsening hirsutism, deepening of her voice, male musculature,
      and male pattern alopecia. Her pertinent past medical history included type 1
      diabetes, hyperlipidemia, and hypertension. Her pertinent past surgical history
      included hysterectomy due to fibroids. On further work-up, her serum total
      testosterone was 506 ng/dL (nl range: 2-45) and free testosterone was 40 pg/mL
      (nl range: 0.1-6.4). After ruling out adrenal causes, the patient underwent an
      empiric bilateral oophorectomy that showed Leydig cell hyperplasia on pathology.
      Six weeks postoperatively, serum testosterone was undetectable with significant
      clinical improvement. Conclusion. Postmenopausal hyperandrogenism can be the
      result of numerous etiologies ranging from normal physiologic changes to ovarian
      or rarely adrenal tumors. Our patient was found to have Leydig cell hyperplasia
      of her ovaries, a rarely reported cause of virilization. 

PMID- 25045550
TI  - Complex variant of Philadelphia translocation involving chromosomes 9, 12, and 22
      in a case with chronic myeloid leukaemia.
AB  - Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in
      the broader diagnostic category of myeloproliferative neoplasms, associated with
      fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the
      formation of the Philadelphia (Ph) chromosome. In 2-10% of CML cases, the fusion
      gene arises in connection with a variant translocation, involving chromosomes 9,
      22, and one or more different chromosomes; consequently, the Ph chromosome could
      be masked within a complex chromosome rearrangement. In cases with variant Ph
      translocation a deletion on der(9) may be more frequently observed than in cases
      with the classical one. Herein we describe a novel case of CML with complex
      variant Ph translocation involving chromosomes 9, 12, and 22. We present the
      hematologic response and cytogenetic response after Imatinib treatment. We also
      speculated the mechanism which had originated the chromosome rearrangement. 

PMID- 25045551
TI  - A Case of Transient, Isolated Cranial Nerve VI Palsy due to Skull Base
      Osteomyelitis.
AB  - Otitis externa affects both children and adults. It is often treated with topical
      antibiotics, with good clinical outcomes. When a patient fails to respond to the
      treatment, otitis externa can progress to malignant otitis externa. The common
      symptoms of skull bone osteomyelitis include ear ache, facial pain, and cranial
      nerve palsies. However, an isolated cranial nerve is rare. Herein, we report a
      case of 54-year-old female who presented with left cranial nerve VI palsy due to
      skull base osteomyelitis which responded to antibiotic therapy. 

PMID- 25045552
TI  - IgG4-Related Tubulointerstitial Nephritis Associated with Membranous Nephropathy
      in Two Patients: Remission after Administering a Combination of Steroid and
      Mizoribine.
AB  - We report two cases of Japanese men who presented with proteinuria, eosinophilia,
      hypocomplementemia, and high serum immunoglobulin G4 (IgG4) concentration and
      were diagnosed with membranous nephropathy associated with IgG4-related
      tubulointerstitial nephritis on renal biopsy. The typical renal lesions of IgG4
      related disease are tubulointerstitial nephritis, which improves remarkably with
      steroid therapy, and occasional glomerular changes. In our two cases, renal
      biopsy revealed IgG4-positive immune complex deposits in glomeruli in a pattern
      of membranous nephropathy and concurrent tubulointerstitial nephritis with IgG4
      plasma cells. In both cases, proteinuria persisted with initial prednisolone
      treatment and was resolved only after the addition of mizoribine. We report the
      first two cases in which the combination of prednisolone and mizoribine was
      effective for treating membranous nephropathy associated with IgG4-related
      tubulointerstitial nephritis. 

PMID- 25045553
TI  - Case report on renal failure reversal in lambda chain multiple myeloma with
      bortezomib and dexamethasone.
AB  - Renal failure (RF) reversal in multiple myeloma (MM) is associated with an
      improved prognosis. Light chain myeloma, serum creatinine (SCr) > 4 mg/dL,
      extensive proteinuria, early infections, and certain renal biopsy findings are
      associated with lower rates of RF reversal. Our patient is a 67-year-old female
      with multiple poor prognostic factors for RF reversal who demonstrated a rapid
      renal response with bortezomib and dexamethasone (BD) regimen. She presented
      initially with altered mental status. On exam, she appeared lethargic and
      dehydrated and had generalized tenderness. She had been taking ibuprofen as
      needed for pain for a few weeks. Labs showed a white cell count-18,900/MUL with
      no bandemia, hemoglobin 10.8 gm/dL, potassium-6.7 mEq/L, bicarbonate-15 mEq/L,
      blood urea nitrogen-62 mg/dL, SCr-5.6 mg/dL (baseline: 1.10), and corrected
      calcium-11.8 mg/dL. A rapid flu test was positive. Imaging studies were
      unremarkable. Her EKG showed sinus tachycardia and her urinalysis was
      unremarkable. The unexplained RF in an elderly individual in conjunction with
      hypercalcemia and anemia prompted a MM work-up; eventually, lambda variant MM was
      diagnosed. An immediate (4 days) renal response defined as 50% reduction in SCr
      was noticed after initiation of the BD regimen. 

PMID- 25045554
TI  - Acute Aneurismal Bilateral Subdural Haematoma without Subarachnoid Haemorrhage: A
      Case Report and Review of the Literature.
AB  - Spontaneous pure acute bilateral subdural haematoma (ASDH) without
      intraparenchymal or subarachnoid haemorrhage caused by a ruptured cerebral
      aneurysm is extremely rare. It can follow rupture of different aneurysms
      specially located in anterior incisural space; the most frequently encountered
      location is the PcoA aneurysms as demonstrated in the present case. We present a
      case report of a PcoA aneurysm presenting as pure bilateral ASDH. A high level of
      suspicion for bleeding of arterial origin should be maintained in all cases of
      acute subdural haematoma without history of trauma. The neurological status on
      admission dictates the appropriate timing and methodology of the
      neuroradiological investigations. 

PMID- 25045555
TI  - Recovery of Dysphagia in lateral medullary stroke.
AB  - Lateral medullary stroke is typically associated with increased likelihood of
      occurrence of dysphagia and exhibits the most severe and persistent form.
      Worldwide little research exists on dysphagia in brainstem stroke. An estimated
      15% of all patients admitted to stroke rehabilitation units experience a
      brainstem stroke out of which about 47% suffer from dysphagia. In India, a study
      showed that 22.3% of posterior circulation stroke patients develop dysphagia.
      Dearth of literature on dysphagia and its outcome in brainstem stroke
      particularly lateral medullary stroke motivated the author to present an actual
      case study of a patient who had dysphagia following a lateral medullary infarct.
      This paper documents the severity and management approach of dysphagia in
      brainstem stroke, with traditional dysphagia therapy and VitalStim therapy.
      Despite being diagnosed with a severe form of dysphagia followed by late
      treatment intervention, the patient had complete recovery of the swallowing
      function. 

PMID- 25045556
TI  - Paroxysmal sneezing at the onset of syncopes and transient ischemic attack
      revealing a papillary cardiac fibroelastoma.
AB  - Sneezing can at times be associated with neurological disorders. The "sneeze
      center" is localized in the lateral medulla. We report the case of a 50-year-old
      man who presented three episodes of sneezing, two of them followed by an episode
      of transient gait instability and dizziness and the third one followed by an
      episode of transient left hemiparesis due to fibroelastoma of the aortic cardiac
      valve. To the best of our knowledge, this is the first description of a transient
      ischemic attack due to cardiac papillary fibroelastoma and revealed by violent
      episodes of sneezing. 

PMID- 25045557
TI  - Encephalopathy and Neuropathy due to Glue, Paint Thinner, and Gasoline Sniffing
      in Trinidad and Tobago-MRI Findings.
AB  - A 29-year-old male petrol station pump attendant was admitted with ataxia and
      clinical evidence of a sensorimotor polyneuropathy which developed over the
      preceding 3 months. He had cognitive dysfunction, hearing loss, and cerebellar
      clinical abnormalities that came on slowly over the three years. He had a fifteen
      year history of sniffing mostly glue, occasionally paint thinners, and, in the
      recent two years, gasoline. Magnetic resonance brain imaging showed abnormalities
      of the cerebral cortex, cerebral white matter, corpus callosum, hippocampus,
      brainstem and cerebellar atrophy, hypointensities of basal ganglia, red nuclei,
      and substantia nigra as previously described in toluene sniffing. Abstinence for
      six months led to partial clinical improvement. Clinicians need to be aware of
      this preventable entity which has peculiar radiological findings which are being
      increasingly accepted as typical. 

PMID- 25045558
TI  - Genitourinary tuberculosis: a rare cause of obstructive uropathy in pregnancy.
AB  - Background. A rare but morbid form of extrapulmonary tuberculosis (TB),
      genitourinary TB is an important cause of obstructive uropathy and is likely
      underdiagnosed in pregnancy. Case. A 30-year-old primigravida undergoing
      treatment for active pulmonary TB presented with anuria at 13-14-weeks gestation.
      Bilateral ureteral strictures above the level of the ureterovesicular junctions
      were seen on imaging studies. Given her pulmonary disease, her obstructive
      uropathy was attributed to genitourinary TB. Bilateral percutaneous nephrostomy
      tubes were placed during pregnancy with successful ureteral reimplantation
      postpartum. Conclusion. Genitourinary TB should be considered as an etiology of
      urinary tract pathology during pregnancy, especially in foreign-born and
      immunocompromised persons. Early recognition resulting in prompt treatment can
      prevent further deterioration of maternal renal function and optimize pregnancy
      outcomes. 

PMID- 25045559
TI  - Her-2 positive gastric cancer presented with thrombocytopenia and skin
      involvement: a case report.
AB  - Gastric cancer is the 5th most frequent cancer around the world and the 3rd most
      frequent reason of deaths due to cancer. Every year, about 1 million new cases
      are taking place, with varying geographical distribution. Gastric cancer is often
      metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph
      nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone
      marrow (BM) and cutaneous metastasis are quite seldom. Pancytopenia is a more
      frequent finding identified in BM metastasis of solid organ cancers, and isolated
      thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2) is
      positive in gastric cancer at a rate of 7-34%. Here, we have presented our HER-2
      positive gastric cancer incident which presented with BM and cutaneous
      metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG) involvement except bone
      metastases. 

PMID- 25045560
TI  - Mixed germ cell testicular cancer with left ventricular metastasis presenting
      with embolic stroke and small bowel tumor seeding.
AB  - Testicular germ cell tumors (GCTs) metastasize in a very predictable fashion
      involving the retroperitoneal nodes first followed by hematogenous spread to
      distant organs like lungs, liver, and brain. Metastasis to heart is an extremely
      rare entity for GCT and fewer than 20 cases have been reported in the literature
      so far. We have summarized here a unique case of nonseminomatous germ cell tumor
      (NSGCT) with intracardiac metastasis resulting in systemic macroembolization to
      liver, spleen, brain, bowel and musculoskeletal tissues. This led to multiple
      adverse sequelae including ischemic stroke and bowel perforation. 

PMID- 25045561
TI  - Optic Neuritis Caused by Rathke's Cleft Cyst in Young Adult.
AB  - We report a case of right optic neuritis caused by Rathke's cleft cyst (RCC) in a
      young adult. A 15-year-old boy presented with reduced visual acuity in the right
      eye. He was diagnosed with optic neuritis in the right eye 4 years earlier at
      other clinics before he was referred to our department. During our one-year
      examinations, the cause of the reduced vision in his right eye could not be
      determined conclusively. At the age of 17 years, a RCC was detected by a
      neurosurgeon who specialized in hypophyseal diseases. He underwent microscopic
      transsphenoidal resection of the cyst, and his vision recovered to 1.2 and he has
      had no recurrence for at least 9 months. We suggest that repeated rupturing of
      the RCC was the cause of the optic neuritis, and a RCC can be successfully
      treated by surgery even after 3 years of optic neuritis. 

PMID- 25045562
TI  - Macular oedema related to idiopathic macular telangiectasia type 1 treated with
      dexamethasone intravitreal implant (ozurdex).
AB  - A 65-year-old female presented with visual disturbance in her right eye lasting
      for over 2 months. Following investigations, she was diagnosed with MacTel type 1
      in the right eye. Visual symptoms were refractory to initial treatment with
      intravitreal bevacizumab and thereafter intravtireal triamicinolone. The patient
      was then treated with Ozurdex, following which central macular thickness (CMT)
      decreased (from 397 MUm to 286 MUm) and visual acuity deteriorated (from logMAR
      0.48 to 0.59). At 14 weeks posttreatment with Ozurdex, a recurrence of cystoid
      macular oedema (CMO) was observed. Following a second Ozurdex, visual acuity
      improved (from logMAR 0.7 to 0.64) and CMT decreased (from 349 MUm to 279 MUm).
      An additional recurrence of CMO was observed at eighteen weeks following the
      second Ozurdex. Following a third Ozurdex injection visual acuity deteriorated
      (from logMAR 0.74 to 0.78) and CMT decreased (from 332 MUm to 279 MUm).
      Conclusion. Treatment of macular oedema secondary to MacTel with Ozurdex
      demonstrated promising anatomical outcomes. However, visual outcomes continued to
      gradually deteriorate. 

PMID- 25045563
TI  - Simplified technique for sealing corneal perforations using a fibrin glue
      assisted amniotic membrane transplant-plug.
AB  - Purpose. To describe a surgical technique using amniotic membrane transplant
      (AMT) with fibrin glue (FG) for treating smaller corneal perforations more
      practically and appropriately filling the defect. Method. A patient with
      noninfectious central corneal perforation, in 1 mm in diameter, was treated with
      FG-assisted AMT-plug. An AMT was folded in on itself twice by using FG then a
      small piece of this FG-AMT mixture was cut to maintain an appropriate plug for
      the site of the corneal perforation. The FG-assisted AMT-plug was placed in the
      perforation area by using FG. An amniotic membrane patch was placed over the
      plug, which was then secured by a bandage contact lens. Result. Surgery to
      restore corneal stromal thickness without recurrence of perforation. Conclusion.
      The FG-assisted AMT-plug allowed a successful repair of 1 mm in diameter corneal
      perforation. This technique was easily performed, thus seeming to be a good
      alternative to treat corneal perforations with restoring corneal thickness. 

PMID- 25045564
TI  - The Relationship between Osteoporosis and Osteoarthritis of the Knee: A Report of
      2 Cases with Suspected Osteonecrosis.
AB  - Knee specimens of two osteoporotic patients who underwent unilateral knee
      arthroplasty for suspected osteonecrosis of the knee were examined
      histologically. Preoperative findings of magnetic resonance images in both
      patients were consistent with the diagnosis of osteonecrosis of the medial
      femoral condyles, although plain X-rays showed minimal degenerative changes. In
      both patients, preoperative bone mineral densities of the femoral condyle and
      proximal tibia of the affected side were lower than those of the unaffected side.
      Pathological examination of the resected femoral condyle and proximal tibia
      showed almost intact joint cartilage, healing of the collapsed subchondral bone,
      and significant trabecular bone loss. Histologically, no evidence of
      osteonecrosis, including empty lacunae of the trabecular bone, was observed.
      These findings indicated that subchondral bone collapse caused by osteoporosis,
      but not osteonecrosis, initiated the osteoarthritic change of the affected knee.
      This report emphasizes that there may be cases of progressive local
      osteoarthritis caused by fracture of subchondral bone because of osteoporosis. 

PMID- 25045565
TI  - Intradural extramedullary capillary hemangioma in the upper thoracic spine: a
      review of the literature.
AB  - Capillary hemangiomas are benign tumors found in the skin and soft tissues in
      younger people. They occur in the central nervous system only rarely, and
      intradural occurrence is extremely rare. We report here a 60-year-old man
      presenting with thoracic girdle pain and progressive gait disturbance. Magnetic
      resonance images of the thoracic spine showed a 12 * 8 * 20 mm, well-defined
      intradural mass at the T2 level, compressing the spinal cord laterally. Relative
      to the spinal cord, the mass was hypo- to isointense on T1-weighted images and
      relatively hyperintense on T2-weighted images, with strong enhancement on
      contrast-enhanced T1-weighted images. The patient underwent T1-2 hemilaminectomy
      with resection of the intradural extramedullary tumor, which showed
      characteristics of a capillary hemangioma on histologic examination. The
      patient's symptoms improved following the surgery and no clinical or radiological
      evidence of recurrence was noted at the 2-year follow-up. We present this case
      with a review of the literature, highlighting features for differential
      diagnosis. 

PMID- 25045566
TI  - Minimally Invasive Microendoscopic Resection of the Transverse Process for
      Treatment of Low Back Pain with Bertolotti's Syndrome.
AB  - Bertolotti's syndrome is characterized by anomalous enlargement of the transverse
      process of the most caudal lumbar segment, causing chronic and persistent low
      back pain or sciatica. We describe the case of a 45-year-old woman who presented
      with left sciatic pain and low back pain due to a recurrent lumbar disc
      herniation at L4-5 with Bertolotti's syndrome. Selective L5 nerve root block and
      local injection of lidocaine into the articulation between the transverse process
      and sacral ala temporarily relieved the left sciatic pain and low back pain,
      respectively. To confirm the effect of local injection on low back pain, we gave
      a second local injection, which once again relieved the low back pain.
      Microendoscopic resection of the pseudoarticulation region and discectomy
      successfully relieved all symptoms. This report illustrates the effectiveness of
      minimally invasive resection of the transverse process for the treatment of low
      back pain with Bertolotti's syndrome. 

PMID- 25045567
TI  - Middle ear adenoma: case report and discussion.
AB  - Introduction. Despite modern radiological workup, surgeons can still be surprised
      by intraoperative findings or by the pathologist's report. Materials & Methods.
      We describe the case of a 52-year-old male who was referred to our clinic with a
      single sided conductive hearing loss. He ultimately underwent middle ear
      exploration and excision of a middle ear tumour followed by second look and
      ossiculoplasty a year later. Results. Though preoperative CT and MRI scanning
      were suggestive of a congenital cholesteatoma, the pathologist's report diagnosed
      a middle ear adenoma. Discussion. Middle ear glandular tumors are extremely rare
      and, despite numerous histological techniques, continue to defy satisfactory
      classification. Most surgeons advocate surgical excision though evidence of the
      tumour's natural course and risk of recurrence is lacking. 

PMID- 25045568
TI  - Bilateral congenital absence of the stapes superstructure in two siblings.
AB  - Middle ear ossicle malformations are an uncommon event. Among them, the
      congenital absence of the stapes is a very rare condition that is seldom
      described in the literature. We report the cases of two women, aged 19 and 22 ,
      who presented with a long history of conductive deafness. An exploratory
      tympanotomy was performed and the absence of the stapes superstructure and an
      abnormal position of the facial nerve could be observed. A bone anchored hearing
      aid (BAHA) was implanted in both patients with good results. It is believed that
      stapes agenesis is related to an abnormal development of the facial nerve, which
      by the 5th to 6th week of gestation would interpose between the otic capsule and
      the stapes blastema, preventing these structures from contacting. A long history
      of nonprogressive hearing loss from birth or early childhood is the key to reach
      a diagnosis. Several treatment options have been described. The authors opted for
      a hearing aid due to the high risk of facial nerve lesion, with good functional
      results. 

PMID- 25045569
TI  - Massive multinodular head and neck recurrence of parotid gland pleomorphic
      adenoma: a case report.
AB  - Introduction. The optimal initial management of parotid pleomorphic adenomas
      reduces the risk of recurrence and malignant transformation. Surgery of
      recurrence can be difficult in multinodular disseminated forms. Case Report. A 67
      years-old patient was referred for management of a large multifocal recurrence of
      a pleomorphic adenoma operated on 23 years ago. The clinical and radiological
      assessment found parapharyngeal, infratemporal, and prestyloid invasion, with
      nodules in the sternocleidomastoid muscle. Excision by transmandibular approach
      was performed. The pathologist found a multinodular recurrent pleomorphic adenoma
      without criteria of malignancy. Postoperative radiotherapy was performed.
      Discussion. Multinodular forms and incomplete resections are the most important
      factors that are thought to predispose to recurrence. A precise analysis of the
      extension by preoperative MRI is essential. Adjuvant radiotherapy can be given in
      these recurrent multifocal forms. 

PMID- 25045570
TI  - An Unusual Case of Systemic Inflammatory Myofibroblastic Tumor with Successful
      Treatment with ALK-Inhibitor.
AB  - Systemic inflammatory myofibroblastic tumor is an exceedingly rare entity. A 45
      year-old Hispanic female presented with a 6-month history of left-sided thigh
      pain, low back pain, and generalized weakness. PET/CT scan revealed abnormal
      activity in the liver, adrenal gland, and pancreas. MRI of the abdomen
      demonstrated two 6-7 cm masses in the liver. MRI of the lumbar spine demonstrated
      lesions in the L2 to L4 spinous processes, paraspinal muscles, and subcutaneous
      tissues, as well as an 8 mm enhancing intradural lesion at T11, all thought to be
      metastatic disease. A biopsy of the liver showed portal tract expansion by a
      spindle cell proliferation rich in inflammation. Tumor cells showed
      immunoreactivity for smooth muscle actin and anaplastic lymphoma kinase 1 (ALK1).
      Tissue from the L5 vertebra showed a process histologically identical to that
      seen in the liver. FISH analysis of these lesions demonstrated an ALK (2p23) gene
      rearrangement. The patient was successfully treated with an ALK-inhibitor,
      Crizotinib, and is now in complete remission. We present the first reported case,
      to our knowledge, of inflammatory myofibroblastic tumor with systemic
      manifestations and ALK translocation. This case is a prime example of how
      personalized medicine has vastly improved patient care through the use of
      molecular-targeted therapy. 

PMID- 25045571
TI  - Spontaneous rupture of the spleen masquerading as a pulmonary infection.
AB  - Atraumatic rupture of a normal spleen represents a rare clinical phenomenon. We
      report on an atypical presentation of a spontaneous splenic rupture in a 44-year
      old previously healthy Greek male admitted to the emergency department due to
      left-sided pleuritic thoracic pain in the course of a pneumonia diagnosed 2 days
      before. During his stay, pain extended to the epigastric region. Abdominal
      examination revealed generalized tenderness. We presume that coughing secondary
      to respiratory infection was the main factor that precipitated splenic rupture.
      Despite the rarity of the condition physicians have to consider the diagnosis of
      spontaneous nontraumatic splenic rupture when they encounter healthy patients
      with nonspecific lower thoracic or abdominal pain. Prompt diagnosis is essential
      for a better outcome. 

PMID- 25045572
TI  - ABO-Incompatible Living Donor Liver Transplantation from Hepatitis B Core
      Antibody Positive Donor to Hepatitis C Liver Cirrhosis Recipient: A Case Report.
AB  - Herein, we describe an extremely rare experience of a patient with liver
      cirrhosis from hepatitis C virus (LC-HCV) who underwent an ABO-incompatible
      living donor liver transplantation (ABO-I-LDLT) using a hepatitis B core antibody
      (HBc-Ab) positive donor's liver graft. A 47-year-old Japanese woman with end
      stage LC-HCV, as a recipient, was preoperatively administered rituximab,
      mycophenolate mofetil, and steroids without plasma exchange. A routine ABO-I-LDLT
      procedure was applied using her daughter's HBc-Ab positive liver graft.
      Prophylaxis of the hepatitis B virus (HBV) infection using hepatitis B
      immunoglobulin (HBIG) and entecavir had been properly administered. Three months
      after the ABO-I-LDLT, HCV hepatitis relapsed. To date, this patient has been
      under antiviral therapy and prophylaxis of HBV infection using HBIG, while
      entecavir has been continued. The cognitions and techniques with regard to ABO-I
      LDLT, prophylaxis of HBV cross infection, various patterns of immunosuppression,
      and antiviral therapy for HCV relapse are indispensable in managing a transplant
      recipient. According to the prophylaxis of HBV cross infection under ABO-I-LDLT,
      it may be very important to keep the HBs-Ab titer higher than usual for HBV naive
      recipients, because severe systemic immunosuppression can cause de novo
      hepatitis. 

PMID- 25045573
TI  - Primary vesical actinomycosis in a 23-year-old man.
AB  - Introduction. Actinomycosis can affect any organ of the body, although cutaneous
      fistulas are common in actinomycotic infections, and other organs such as the
      bladder are only rarely involved. Case Presentation. Herein we report and discuss
      a young male patient with primary vesical actinomycosis. A 23-year-old man was
      hospitalized complaining of intermittent gross hematuria over a 6-month duration.
      The patient underwent a cystoscopic examination under general anesthesia; an
      edematous, hyperemic, wide-based mass, which protruded from the dome of the
      bladder, was seen and incompletely resected. The histopathological examination of
      the material showed Actinomyces organisms surrounded by inflammation and a
      photomicrograph showed the microorganism. After confirmation of bladder
      actinomycosis, the patient received penicillin. A CT scan of the abdomen and
      pelvis showed no evidence of the mass at the postoperative 6th month. Cystoscopic
      examination showed complete healing of the transurethral resection area at the
      dome of the bladder. Conclusion. In conclusion, we believe that the gold standard
      treatment for vesical actinomycosis should include the combination of a
      transurethral resection of the mass and long-term penicillin treatment. 

PMID- 25045574
TI  - 5-Aminosalicylic Acid Inhibits Acute Clostridium difficile Toxin A-Induced
      Colitis in Rats.
AB  - We tested the hypothesis that 5-aminosalicylic acid (5-ASA) inhibits toxin A
      induced generation of colonic leukotriene B4 (LTB4) and toxin A colitis in rats.
      Isolated colonic segments in anesthetized rats were treated intraluminally with
      toxin A for 3 hours with or without 30 minutes of pretreatment with either 5-ASA
      or sulfapyridine and then colonic tissue levels of LTB4 were measured and
      inflammation was assessed. Separately, sulfasalazine was administered to rats in
      their drinking water for 5 days, isolated colonic segments were then prepared,
      toxin A was administered, and inflammation was assessed as before. Pretreatment
      with 5-ASA inhibited toxin A-induced increased tissue LTB4 concentration in the
      colon. Sulfasalazine and 5-ASA but not sulfapyridine significantly inhibited
      toxin A colitis. However, pretreatment with 5-ASA did not protect against direct
      TRPV1-mediated colitis caused by capsaicin. Toxin A stimulated the release of
      substance P (SP), and this effect was also inhibited by sulfasalazine and 5-ASA
      but not by sulfapyridine. Thus, toxin A stimulates colonic LTB4 resulting in
      activation of TRPV1, release of SP, and colitis. Inhibition of 5-LO by 5-ASA
      disrupts this pathway and supports the concept that LTB4 activation of TRPV1
      plays a role in toxin A colitis. 

PMID- 25045575
TI  - Does the Use of Dihydroartemisinin-Piperaquine in Treating Patients with
      Uncomplicated falciparum Malaria Reduce the Risk for Recurrent New falciparum
      Infection More Than Artemether-Lumefantrine?
AB  - Malaria contributes significantly to the global disease burden. The World Health
      Organization recommended the use of artemisinin-based combination therapies
      (ACTs) for treatment of uncomplicated falciparum malaria a decade ago in response
      to problems of drug resistance. This review compared two of the ACTs
      Dihydroartemisinin-Piperaquine (DP) and Artemether-Lumefantrine (AL) to provide
      evidence which one has the ability to offer superior posttreatment prophylaxis at
      28 and 42 days posttreatment. Four databases (MEDLINE, EMBASE, Cochrane Database
      and Global Health) were searched on June 2, 2013 and a total of seven randomized
      controlled trials conducted in sub-Sahara Africa were included. Results involving
      2, 340 participants indicates that reduction in risk for recurrent new falciparum
      infections (RNIs) was 79% at day 28 in favour of DP [RR, 0.21; 95% CI: 0.14 to
      0.32, P < 0.001], and at day 42 was 44% favouring DP [RR, 0.56; 95% CI: 0.34 to
      0.90; P = 0.02]. No significant difference was seen in treatment failure rates
      between the two drugs at days 28 and 42. It is concluded that use of DP offers
      superior posttreatment prophylaxis compared to AL in the study areas. Hence DP
      can help reduce malaria cases in such areas more than AL. 

PMID- 25045577
TI  - Fever Screening and Detection of Febrile Arrivals at an International Airport in
      Korea: Association among Self-reported Fever, Infrared Thermal Camera Scanning,
      and Tympanic Temperature.
AB  - OBJECTIVES: The purpose of this research was to measure fever prevalence and the
      effectiveness of a fever screening procedure in detecting febrile arrivals at an
      international airport in Korea. METHODS: Data were retrieved from arrivals'
      health declaration forms and questionnaires for febrile arrivals at an
      international airport collected by a national quarantine station during the year
      2012. Self-reported health declaration forms were returned by 355,887 arrivals
      (61% of the total arrivals). Of these, 608 symptomatic arrivals (0.2%) including
      6 febrile arrivals were analyzed. RESULTS: Fever prevalence at an international
      airport in Korea was 0.002%. Self-reported fever was significantly positively
      associated with tympanic temperature (p<0.001). The difference between the
      thermal camera temperature (36.83 degrees C) and tympanic (or ear) temperature
      (38.14 degrees C) was not statistically significant. CONCLUSIONS: The findings
      imply that a procedure for mass detection of fever such as self-reported
      questionnaires and thermal camera scanning may serve as an effective tool for
      detecting febrile arrivals at quarantine stations. Future research can benefit
      from looking at the sensitivity, specificity, positive predictive value, and
      negative predictive value of the entry screening system. OBJECTIVES: The purpose
      of this research was to measure fever prevalence and the effectiveness of a fever
      screening procedure in detecting febrile arrivals at an international airport in
      Korea. METHODS: Data were retrieved from arrivals' health declaration forms and
      questionnaires for febrile arrivals at an international airport collected by a
      national quarantine station during the year 2012. Self-reported health
      declaration forms were returned by 355,887 arrivals (61% of the total arrivals).
      Of these, 608 symptomatic arrivals (0.2%) including 6 febrile arrivals were
      analyzed. RESULTS: Fever prevalence at an international airport in Korea was
      0.002%. Self-reported fever was significantly positively associated with tympanic
      temperature (p<0.001). The difference between the thermal camera temperature
      (36.83 degrees C) and tympanic (or ear) temperature (38.14 degrees C) was not
      statistically significant. CONCLUSIONS: The findings imply that a procedure for
      mass detection of fever such as self-reported questionnaires and thermal camera
      scanning may serve as an effective tool for detecting febrile arrivals at
      quarantine stations. Future research can benefit from looking at the sensitivity,
      specificity, positive predictive value, and negative predictive value of the
      entry screening system.

PMID- 25045576
TI  - The cardioprotective actions of hydrogen sulfide in acute myocardial infarction
      and heart failure.
AB  - It has now become universally accepted that hydrogen sulfide (H2S), previously
      considered only as a lethal toxin, has robust cytoprotective actions in multiple
      organ systems. The diverse signaling profile of H2S impacts multiple pathways to
      exert cytoprotective actions in a number of pathological states. This paper will
      review the recently described cardioprotective actions of hydrogen sulfide in
      both myocardial ischemia/reperfusion injury and congestive heart failure. 

PMID- 25045578
TI  - Effects of antibiotic consumption on children 2-8 years of age developing asthma.
AB  - OBJECTIVES: Antibiotic exposure in children is a possible contributor to the
      increasing asthma prevalence in several countries. The present study aimed to
      investigate the association between antibiotic exposure and the risk of
      developing childhood asthma at 2-8 years of age. METHODS: A case-control study
      was undertaken among children aged 2-8 years old between March and September 2010
      in the Urmia district in the northwest of Iran. The cases were doctor-diagnosed
      asthmatic children based on Global Initiative for Asthma criteria (n=207), and
      the controls were children without respiratory symptoms (n=400) selected by
      frequency matching by age and gender. Clinical data including antibiotic exposure
      was collected by a validated and reliable questionnaire, which was completed by
      interviewing parents/guardians. RESULTS: Antibiotic consumption during the first
      year of life increased the odds ratio [OR] of asthma symptoms at 2-8 years of age
      (crude OR, 2.26; 95% confidence interval [CI], 1.53-3.35; p<0.01), and the
      strength of association was similar after adjusting for a family history of
      asthma or atopic disorder, preterm delivery, birth order, and delivery method
      (adjusted OR, 1.91; 95% CI, 1.27-2.88; p=0.03). CONCLUSIONS: Our study suggests
      that antibiotic consumption in children was associated with an increased risk of
      childhood asthma, and an additional confirmative study is needed.

PMID- 25045579
TI  - ICG-liver test versus new biomarkers as prognostic markers for prolonged length
      of stay in critically ill patients - a prospective study of accuracy for
      prediction of length of stay in the ICU.
AB  - BACKGROUND: Prognostic abilities of medical parameters, which are scoring
      systems, measurements and biomarkers, are important for stratifying critically
      ill patients. Indocyanine green plasma disappearance (ICG-PDR) is an established
      clinical tool for the assessment of liver perfusion and function. Copeptin, MR
      proANP and pro-ADM are biomarkers whose prognostic value is still unclear. The
      goal of this prospective study was to evaluate ICG-PDR, copeptin, MR-proANP and
      pro-ADM to predict prolonged length of stay (pLOS) in the ICU. METHODS: This
      study was conducted as a prospective single center study including 110
      consecutively admitted ICU patients. Primary endpoint was prolonged length of
      stay (pLOS) in the ICU, defined as more than three days of stay there. RESULTS:
      ROC analysis showed an AUC of 0.73 for ICG-PDR, 0.70 for SAPS II, 0.65 for MR
      proANP, 0.64 for pro-ADM and 0.54 for copeptin for pLOS in the ICU. CONCLUSIONS:
      The prediction of pLOS in the ICU might be better by means of ICG-PDR than with
      the new biomarkers copeptin, MR-proANP or pro-ADM. Nevertheless, there is more
      need for research to evaluate whether ICG-PDR is an overall prognostic marker for
      pLOS. TRIAL REGISTRATION: (ClinicalTrials.gov number, NCT01126554).

PMID- 25045580
TI  - Ethical reflections on end-of-life signs and symptoms in the intensive care
      setting: a place for neuromuscular blockers?
AB  - The death of a loved one is often an ordeal and a tragedy for those who witness
      it, as death is not merely the end of a life, but also the end of an existence,
      the loss of a unique individual who is special and irreplaceable. In some
      situations, end-of-life signs, such as agonal gasps, can be an almost unbearable
      "sight" because the physical manifestations are hard to watch and can lead to
      subjective interpretation and irrational fears. Ethical unease arises as the
      dying patient falls prey to death throes and to the manifestations of ebbing life
      and the physician can only stand by and watch. From this point on, medicine can
      put an end to suffering by the use of neuromuscular blockade, but in so doing
      life ceases at the same time. It is difficult, however, not to respond to the
      distress of loved ones and caregivers. The ethical problem then becomes the shift
      from the original ethical concern, i.e. the dying patient, to the patient's loved
      ones. Is such a rupture due to a difference in nature or a difference in degree,
      given that the dying patient remains a person and not a thing as long as the body
      continues to lead its own life, expressed through movement and sound? Because
      there cannot be any simple and unequivocal answer to this question, the SRLF
      Ethics Commission is offering ethical reflections on end-of-life signs and
      symptoms in the intensive care setting, and on the use of neuromuscular blockade
      in this context, with presentations on the subject by two philosophers and
      members of the SRLF Ethics Commission, Ms Lise Haddad and Prof Dominique
      Folscheid. The SRLF Ethics Commission hopes to provide food for thought for
      everyone on this topic, which undoubtedly calls for further contributions, the
      aim being not to provide ready-made solutions or policy, but rather to allow
      everyone to ponder this question in all conscience. 

PMID- 23390591
TI  - A Method to Produce and Purify Full-Length Recombinant Alpha Dystroglycan:
      Analysis of N- and O-Linked Monosaccharide Composition in CHO Cells with or
      without LARGE Overexpression.
AB  - alpha dystroglycan (alphaDG) is part of the dystrophin-associated glycoprotein
      (DAG) complex, a series of cytoskeletal, transmembrane, and membrane-associated
      proteins that serve to link the extracellular matrix (ECM) surrounding individual
      skeletal myofibers to the intracellular F-actin cytoskeleton. Glycosylation and
      ECM protein binding to alphaDG are regulated by a number of genes that, when
      defective, give rise to congenital or limb-girdle forms of muscular dystrophy
      termed dystroglycanopathies. One such dystroglycanopathy gene is LARGE. Here, we
      describe a method to produce and purify full-length, furin-resistant, recombinant
      alphaDG from CHO cells and CHO cells overexpressing LARGE (CHO-LARGE). In
      addition, we analyze the O- and N-linked monosaccharide composition of such
      proteins. alphaDG purified from CHO-LARGE cells had increased molar content of
      xylose and fucose relative to CHO, while no significant changes were found in N
      linked monosaccharides. Glucuronic acid could not be quantified by the methods
      used. These studies describe a method to produce and purify the milligram amounts
      of alphaDG needed for certain biochemical methods, including monosaccharide
      analysis. Key words: Dystroglycan, muscular dystrophy, xylose, fucose, laminin,
      LARGE Correspondence: Paul.Martin@nationwidechildrens.org. 

PMID- 25045581
TI  - Environmental-stress-induced Chromatin Regulation and its Heritability.
AB  - Chromatin is subject to proofreading and repair mechanisms during the process of
      DNA replication, as well as repair to maintain genetic and epigenetic information
      and genome stability. The dynamic structure of chromatin modulates various
      nuclear processes, including transcription and replication, by altering the
      accessibility of the DNA to regulatory factors. Structural changes in chromatin
      are affected by the chemical modification of histone proteins and DNA, remodeling
      of nucleosomes, incorporation of variant histones, noncoding RNAs, and nonhistone
      DNA-binding proteins. Phenotypic diversity and fidelity can be balanced by
      controlling stochastic switching of chromatin structure and dynamics in response
      to the environmental disruptors and endogenous stresses. The dynamic chromatin
      remodeling can, therefore, serve as a sensor, through which environmental and/or
      metabolic agents can alter gene expression, leading to global cellular changes
      involving multiple interactive networks. Furthermore its recent evidence also
      suggests that the epigenetic changes are heritable during the development. This
      review will discuss the environmental sensing system for chromatin regulation and
      genetic and epigenetic controls from developmental perspectives.

PMID- 23653281
TI  - Is a motor criterion essential for the diagnosis of clinical huntington disease?
AB  - While there has been a guideline for laboratory/genetic diagnosis of Huntington
      Disease (HD) since 1998, no such statement exists for the diagnosis of clinical
      HD. Informally, the most frequently used criteria for diagnosis of clinical HD is
      'Motor 4' within the Unified Huntington Disease Rating Scale '99 (motor), made
      when the rater is highly confident that 'motor abnormalities observed are
      unequivocal signs of HD'. Recent studies involving pre-manifest individuals
      illustrated the shortcomings of this motor-only diagnostic approach. For
      instance, PREDICT-HD found cognitive changes decades before the expected date of
      motor diagnosis. Using a number of case studies, we highlight some of the
      subtleties involved in diagnosing clinical HD, in the absence of unequivocal
      motor signs for HD. New, broader, criteria for the diagnosis of clinical HD would
      be helpful in many ways. However its formulation will need to flexible rather
      than prescriptive, and will require extensive consultation with clinicians and
      families with HD. 

PMID- 24057032
TI  - Generation of embryonic stem cells and mice for duchenne research.
AB  - Duchenne muscular dystrophy (DMD) is a muscle-wasting disease in which muscle is
      continuously damaged, resulting in loss of muscle tissue and function. Antisense
      mediated exon skipping is a promising therapeutic approach for DMD. This method
      uses sequence specific antisense oligonucleotides (AONs) to reframe disrupted
      dystrophin transcripts. As AONs function in a sequence specific manner, human
      specific AONs cannot be tested in the mdx mouse, which carries a mutation in the
      murine Dmd gene. We have previously generated a mouse model carrying the complete
      human DMD gene (hDMD mouse) integrated in the mouse genome to overcome this
      problem. However, as this is not a disease model, it cannot be used to study the
      effect of AON treatment on protein level and muscle function. Therefore, our long
      term goal is to generate deletions in the human DMD gene in a mouse carrying the
      hDMD gene in an mdx background. Towards this aim, we generated a male ES cell
      line carrying the hDMD gene while having the mdx point mutation. Inheritance of
      the hDMD gene by the ES cell was confirmed both on DNA and mRNA level. Quality
      control of the ES cells revealed that the pluripotency marker genes Oct-4 and
      Nanog are well expressed and that 85% of cells have 40 chromosomes. Germ line
      competence of this cell line has been confirmed, and 2 mice strains were derived
      from this cell line and crossed back on a C57BL6 background: hDMD/mdx and
      mdx(BL6). 

PMID- 25045586
TI  - Rapid health needs assessment experience in 11 august 2012 East azerbaijan
      earthquakes: a qualitative study.
AB  - INTRODUCTION: In disasters, health care providers need to find out the essential
      needs of the affected populations through Rapid Health Needs Assessment (RHNA).
      In East Azerbaijan earthquakes, a rapid assessment was performed by the
      provincial health system. The main purpose of this study was to explore the RHNA
      challenges. METHODS: In this qualitative study (Grounded theory), data was
      collected through semi-structured interviews with purposely selected health care
      workers. The data collection process continued until data saturation. All
      interviews were recorded and then transcribed. The Colaizzi's descriptive method
      was used to analyze the data. RESULTS: The themes emerged from the analysis of
      the interviews were: 1) Logistic problems 2) Lack of RHNA tools 3) Inherent
      difficulty of RHNA in disaster situations 4) Lack of preparedness and 5) Lack of
      coordination between different organizations. These challenges result in
      inapplicable use of RHNA results. CONCLUSION: The most important challenge in
      this RHNA process was the lack of East Azerbaijan health center preparedness.
      Although they were familiar with the importance of RHNA, they did not have any
      plans for conducting RHNA.

PMID- 24162793
TI  - Critical resources for hospital surge capacity: an expert consensus panel.
AB  - BACKGROUND: Hospital surge capacity (HSC) is dependent on the ability to increase
      or conserve resources. The hospital surge model put forth by the Agency for
      Healthcare Research and Quality (AHRQ) estimates the resources needed by
      hospitals to treat casualties resulting from 13 national planning scenarios.
      However, emergency planners need to know which hospital resource are most
      critical in order to develop a more accurate plan for HSC in the event of a
      disaster. OBJECTIVE: To identify critical hospital resources required in four
      specific catastrophic scenarios; namely, pandemic influenza, radiation,
      explosive, and nerve gas. METHODS: We convened an expert consensus panel
      comprised of 23 participants representing health providers (i.e., nurses and
      physicians), administrators, emergency planners, and specialists. Four disaster
      scenarios were examined by the panel. Participants were divided into 4 groups of
      five or six members, each of which were assigned two of four scenarios. They were
      asked to consider 132 hospital patient care resources- extracted from the AHRQ's
      hospital surge model- in order to identify the ones that would be critical in
      their opinion to patient care. The definition for a critical hospital resource
      was the following: absence of the resource is likely to have a major impact on
      patient outcomes, i.e., high likelihood of untoward event, possibly death. For
      items with any disagreement in ranking, we conducted a facilitated discussion
      (modified Delphi technique) until consensus was reached, which was defined as
      more than 50% agreement. Intraclass Correlation Coefficients (ICC) were
      calculated for each scenario, and across all scenarios as a measure of
      participant agreement on critical resources. For the critical resources common to
      all scenarios, Kruskal-Wallis test was performed to measure the distribution of
      scores across all scenarios. RESULTS: Of the 132 hospital resources, 25 were
      considered critical for all four scenarios by more than 50% of the participants.
      The number of hospital resources considered to be critical by consensus varied
      from one scenario to another; 58 for the pandemic influenza scenario, 51 for
      radiation exposure, 41 for explosives, and 35 for nerve gas scenario. Intravenous
      crystalloid solution was the only resource ranked by all participants as critical
      across all scenarios. The agreement in ranking was strong in nerve agent and
      pandemic influenza (ICC= 0.7 in both), and moderate in explosives (ICC= 0.6) and
      radiation (ICC= 0.5). CONCLUSION: In four disaster scenarios, namely, radiation,
      pandemic influenza, explosives, and nerve gas scenarios; supply of as few as 25
      common resources may be considered critical to hospital surge capacity. The
      absence of any these resources may compromise patient care. More studies are
      needed to identify critical hospital resources in other disaster scenarios.

PMID- 25045587
TI  - Carbon monoxide poisoning and flooding: changes in risk before, during and after
      flooding require appropriate public health interventions.
AB  - Introduction While many of the acute risks posed by flooding and other disasters
      are well characterised, the burden of carbon monoxide (CO) poisoning and the wide
      range of ways in which this avoidable poisoning can occur around flooding
      episodes is poorly understood, particularly in Europe. The risk to health from CO
      may continue over extended periods of time after flooding and different stages of
      disaster impact and recovery are associated with different hazards. Methods A
      review of the literature was undertaken to describe the changing risk of CO
      poisoning throughout flooding/disaster situations. The key objectives were to
      identify published reports of flood-related carbon monoxide incidents that have
      resulted in a public health impact and to categorise these according to Noji's
      Framework of Disaster Phases (Noji 1997); to summarise and review carbon monoxide
      incidents in Europe associated with flooding in order to understand the burden of
      CO poisoning associated with flooding and power outages; and to summarise those
      strategies in Europe which aim to prevent CO poisoning that have been published
      and/or evaluated. The review identified 23 papers which met its criteria. The
      team also reviewed and discussed relevant government and non-government guidance
      documents. This paper presents a summary of the outcomes and recommendations from
      this review of the literature. Results Papers describing poisonings can be
      considered in terms of the appliance/source of CO or the circumstances leading to
      poisoning.The specific circumstances identified which lead to CO poisoning during
      flooding and other disasters vary according to disaster phase. Three key
      situations were identified in which flooding can lead to CO poisoning; pre
      disaster, emergency/recovery phase and post-recovery/delayed phase. These
      circumstances are described in detail with case studies. This classification of
      situations is important as different public health messages are more appropriate
      at different phases of a disaster. The burden of disease from poisoning caused by
      each potential source and at each phase of a disaster is different. CO poisoning
      is not compulsory and deaths associated with a flood but delayed for a period of
      months, for example due to a damaged boiler, may never be attributed to the flood
      as surveillance often ends once the floodwaters recede. The problem of under
      reporting is crucial to our understanding of flooding-related poisoning. The
      indoor use of portable generators, cooking and heating appliances designed for
      use outdoors during periods of loss of mains power or gas is a particular
      problem. In the recovery phase, equipment for pumping, dehumidifying and drying
      out of properties poses a new risk. In the long term, mortality and morbidity
      associated with the renewed use of boilers which may have suffered covert damage
      in flooding is recognised but very difficult to quantify. Papers evaluating
      interventions were not found and where literature exists on prevention of CO
      poisoning in disaster situations, it is from the USA. Conclusions This paper for
      the first time describes the different risks of CO poisoning posed by the
      different phases of a disaster. There is a specific need to recognise that any
      room in a building can harbour a CO emitting appliance in flooding; wood burners
      and rarely used chimney flues may become particularly problematic following a
      flood. Recommendations 1) Public health workers and policy makers should consider
      establishing toolkits using the CDC toolkit approach; the acceptability of any
      intervention must be evaluated further to guide informed policy. 2) CO poisoning
      must form part of syndromic and event based surveillance systems for flooding and
      should be included in measures of the health impact of flooding. 3) CO monitors
      in the domestic environment should be sited not only in proximity to known CO
      emitters but also in locations where mobile or short term CO emitting appliances
      may be placed, including woodburners and infrequently used fireplaces. 

PMID- 25045588
TI  - Preventing malnutrition in post-conflict, food insecure settings: a case study
      from South Sudan.
AB  - BACKGROUND: Decades of civil conflict compound the challenges of food insecurity
      in South Sudan and contribute to persistent, high levels of child malnutrition.
      As efforts to prevent child malnutrition continue, there is a critical need for
      strategies that effectively supplement the diets of pregnant women and young
      children in transitional, highly food insecure settings like South Sudan.
      METHODS: This mixed-methods case study of four communities in South Sudan reports
      on the diets of children under 2 years of age and explores household-level
      factors including household size, intrahousehold food allocation practices, and
      responses to scarcity that may have significant impact on the effectiveness of
      strategies relying on household ration distribution to supplement the diets of
      pregnant women and children under 2 years of age. RESULTS: Participants reported
      experiencing increased scarcity as a result of prolonged drought and household
      sizes enlarged by the high volume of returning refugees. Although communities
      were receiving monthly household rations through a non-emergency food assistance
      program, most households had exhausted rations less than 30 days after receipt.
      Results showed that more than one half of children 12-17 months and one third of
      children 18-23 months consumed diets consisting of fewer than 4 food groups in
      the last week. Intrahousehold food allocation patterns give children first
      priority at meal times even in times of scarcity, yet adult women, including
      pregnant women, have last priority. DISCUSSION: These findings suggest that
      distribution of supplementary household rations will likely be insufficient to
      effectively supplement the diets of young children and pregnant women in
      particular. In light of the multiple contextual challenges experienced by
      households in transitional, food-insecure settings, these findings support
      recommendations to take a context-specific approach to food assistance
      programming, in which considerations of intrahousehold food allocation patterns
      and broader cultural and environmental factors inform program design.
      Incorporating assessments of intrahousehold food allocation patterns as part of
      needs assessments for food assistance and voucher or cash transfer programs may
      contribute to more effective, context specific programming.

PMID- 25045590
TI  - Long-Term Electrophysiological and Behavioral Analysis on the Improvement of
      Visual Working Memory Load, Training Gains, and Transfer Benefits.
AB  - Recent evidence demonstrates that with training, one can enhance visual working
      memory (VWM) capacity and attention over time in the near transfer tasks. Not
      only do these studies reveal the characteristics of VWM load and the influences
      of training, they may also provide insights into developing effective
      rehabilitation for patients with VWM deficiencies. However, few studies have
      investigated VWM over extended periods of time and evaluated transfer benefits on
      non-trained tasks. Here, we combined behavioral and electroencephalographical
      approaches to investigate VWM load, training gains, and transfer benefits. Our
      results reveal that VWM capacity is directly correlated to the difference of
      event-related potential waveforms. In particular, the "magic number 4" can be
      observed through the contralateral delay amplitude and the average capacity is
      3.25-item over 15 participants. Furthermore, our findings indicate that VWM
      capacity can be improved through training; and after training exercises,
      participants from the training group are able to dramatically improve their
      performance. Likewise, the training effects on non-trained tasks can also be
      observed at the 12th week after training. Therefore, we conclude that
      participants can benefit from training gains, and augmented VWM capacity
      sustained over long periods of time on specific variety of tasks.

PMID- 25045589
TI  - Safeguarding Stem Cell-Based Regenerative Therapy against Iatrogenic
      Cancerogenesis: Transgenic Expression of DNASE1, DNASE1L3, DNASE2, DFFB
      Controlled By POLA1 Promoter in Proliferating and Directed Differentiation
      Resisting Human Autologous Pluripotent Induced Stem Cells Leads to their Death.
AB  - INTRODUCTION: The worst possible complication of using stem cells for
      regenerative therapy is iatrogenic cancerogenesis. The ultimate goal of our work
      is to develop a self-triggering feedback mechanism aimed at causing death of all
      stem cells, which resist directed differentiation, keep proliferating, and can
      grow into tumors. SPECIFIC AIM: The specific aim was threefold: (1) to
      genetically engineer the DNA constructs for the human, recombinant DNASE1,
      DNASE1L3, DNASE2, DFFB controlled by POLA promoter; (2) to bioengineer anti-SSEA
      4 antibody guided vectors delivering transgenes to human undifferentiated and
      proliferating pluripotent stem cells; (3) to cause death of proliferating and
      directed differentiation resisting stem cells by transgenic expression of the
      human recombinant the DNases (hrDNases). METHODS: The DNA constructs for the
      human, recombinant DNASE1, DNASE1L3, DNASE2, DFFB controlled by POLA promoter
      were genetically engineered. The vectors targeting specifically SSEA-4 expressing
      stem cells were bioengineered. The healthy volunteers' bone marrow mononuclear
      cells (BMMCs) were induced into human, autologous, pluripotent stem cells with
      non-integrating plasmids. Directed differentiation of the induced stem cells into
      endothelial cells was accomplished with EGF and BMP. The anti-SSEA 4 antibodies'
      guided DNA vectors delivered the transgenes for the human recombinant DNases'
      into proliferating stem cells. RESULTS: Differentiation of the pluripotent
      induced stem cells into the endothelial cells was verified by highlighting
      formation of tight and adherens junctions through transgenic expression of
      recombinant fluorescent fusion proteins: VE cadherin, claudin, zona occludens 1,
      and catenin. Proliferation of the stem cells was determined through highlighting
      transgenic expression of recombinant fluorescent proteins controlled by POLA
      promoter, while also reporting expression of the transgenes for the hrDNases.
      Expression of the transgenes for the DNases resulted in complete collapse of the
      chromatin architecture and degradation of the proliferating cells' genomic DNA.
      The proliferating stem cells, but not the differentiating ones, were effectively
      induced to die. CONCLUSION: Herein, we describe attaining the proof-of-concept
      for the strategy, whereby transgenic expression of the genetically engineered
      human recombinant DNases in proliferating and directed differentiation resisting
      stem cells leads to their death. This novel strategy reduces the risk of
      iatrogenic neoplasms in stem cell therapy.

PMID- 25045591
TI  - Re-examining Sonographic Cut-off Values for Diagnosing Early Pregnancy Loss.

PMID- 25045592
TI  - Morphine has latent deleterious effects on the ventilatory responses to a hypoxic
      hypercapnic challenge.
AB  - This study explored the concept that morphine has latent deleterious actions on
      the ventilatory control systems that respond to a hypoxic-hypercapnic challenge.
      In this study, we examined the ventilatory responses elicited by hypoxic
      hypercapnic challenge in conscious rats at a time when the effects of morphine
      (10 mg/kg) on arterial blood-gas chemistry and minute ventilation had subsided.
      Morphine induced pronounced changes in arterial blood-gas chemistry (e.g., an
      increase in pCO2, decreases in pO2 and sO2) and decreases in minute ventilation.
      Despite the complete resolution of the morphine-induced changes in arterial blood
      gas chemistry and minute ventilation and almost complete resolution of the
      effects on peak inspiratory flow and peak expiratory flow, subsequent exposure to
      hypoxic-hypercapnic challenge elicited markedly blunted increases in minute
      ventilation and in peak inspiratory and expiratory flows. These findings
      demonstrate that (1) the changes in arterial blood-gas chemistry elicited by
      morphine parallel changes in minute ventilation rather than PIF and PEF, and (2)
      morphine has latent untoward effects on the ventilatory responses to hypoxic
      hypercapnic challenge. These novel findings raise the possibility that patients
      deemed to have recovered from the acute ventilatory depressant effects of
      morphine may still be susceptible to the latent effects of this opioid analgesic.
      The mechanisms underlying these latent effects remain to be elucidated.

PMID- 25045593
TI  - Morphine has latent deleterious effects on the ventilatory responses to a hypoxic
      challenge.
AB  - The aim of this study was to determine whether morphine depresses the ventilatory
      responses elicited by a hypoxic challenge (10% O2, 90% N2) in conscious rats at a
      time when the effects of morphine on arterial blood gas (ABG) chemistry, Alveolar
      arterial (A-a) gradient and minute ventilation (VM) had completely subsided. In
      vehicle-treated rats, each episode of hypoxia stimulated ventilatory function and
      the responses generally subsided during each normoxic period. Morphine (5 mg/kg,
      i.v.) induced an array of depressant effects on ABG chemistry, A-a gradient and
      VM (via decreases in tidal volume). Despite resolution of these morphine-induced
      effects, the first episode of hypoxia elicited substantially smaller increases in
      VM than in vehicle-treated rats, due mainly to smaller increases in frequency of
      breathing. The pattern of ventilatory responses during subsequent episodes of
      hypoxia and normoxia changed substantially in morphine-treated rats. It is
      evident that morphine has latent deleterious effects on ventilatory responses
      elicited by hypoxic challenge.

PMID- 25045595
TI  - Multilevel factors influencing preterm birth in an urban setting.

PMID- 25045594
TI  - What Are We Putting in Our Food That Is Making Us Fat? Food Additives,
      Contaminants, and Other Putative Contributors to Obesity.
AB  - The "chemical obesogen" hypothesis conjectures that synthetic, environmental
      contaminants are contributing to the global epidemic of obesity. In fact,
      intentional food additives (e.g., artificial sweeteners and colors, emulsifiers)
      and unintentional compounds (e.g., bisphenol A, pesticides) are largely unstudied
      in regard to their effects on overall metabolic homeostasis. With that said, many
      of these contaminants have been found to dysregulate endocrine function, insulin
      signaling, and/or adipocyte function. Although momentum for the chemical obesogen
      hypothesis is growing, supportive, evidence-based research is lacking. In order
      to identify noxious synthetic compounds in the environment out of the thousands
      of chemicals that are currently in use, tools and models from toxicology should
      be adopted (e.g., functional high throughput screening methods, zebrafish-based
      assays). Finally, mechanistic insight into obesogen-induced effects will be
      helpful in elucidating their role in the obesity epidemic as well as preventing
      and reversing their effects. 

PMID- 25045596
TI  - Genetic Counseling for Diabetes Mellitus.
AB  - Most diabetes is polygenic in etiology, with (type 1 diabetes, T1DM) or without
      (type 2 diabetes, T2DM) an autoimmune basis. Genetic counseling for diabetes
      generally focuses on providing empiric risk information based on family history
      and/or the effects of maternal hyperglycemia on pregnancy outcome. An estimated
      one to five percent of diabetes is monogenic in nature, e.g., maturity onset
      diabetes of the young (MODY), with molecular testing and etiology-based treatment
      available. However, recent studies show that most monogenic diabetes is
      misdiagnosed as T1DM or T2DM. While efforts are underway to increase the rate of
      diagnosis in the diabetes clinic, genetic counselors and clinical geneticists are
      in a prime position to identify monogenic cases through targeted questions during
      a family history combined with working in conjunction with diabetes professionals
      to diagnose and assure proper treatment and familial risk assessment for
      individuals with monogenic diabetes.

PMID- 25045597
TI  - Rare Variants and Transcriptomics in Alzheimer disease.
AB  - Alzheimer disease (AD) is the most common dementia in the elderly, still without
      effective treatment. Early-onset AD (EOAD) is caused by mutations in the genes
      APP, PSEN1 and PSEN2. Genome-wide association studies have identified >20 late
      onset AD (LOAD) susceptibility genes with common variants of small risk, with the
      exception of APOE. We review rare susceptibility variants in LOAD with larger
      effects that have been recently identified in the EOAD gene APP and the newly
      discovered AD genes TREM2 and PLD3. Human genetic studies now consistently
      support the amyloid hypothesis of AD for both EOAD and LOAD. Moreover, they
      identified biological processes that overlap with human transcriptomics studies
      in AD across different tissues, such as inflammation, cytoskeletal organization,
      synaptic functions, etc. Transcriptomic profiles of pre-symptomatic AD-associated
      variant carriers already reflect specific molecular mechanisms reminiscent to
      those of AD patients. This might provide an avenue for personalized medicine.

PMID- 25045598
TI  - LESSONS LEARNED ABOUT PUBLIC HEALTH FROM ONLINE CROWD SURVEILLANCE.
AB  - The Internet has forever changed the way people access information and make
      decisions about their healthcare needs. Patients now share information about
      their health at unprecedented rates on social networking sites such as Twitter
      and Facebook and on medical discussion boards. In addition to explicitly shared
      information about health conditions through posts, patients reveal data on their
      inner fears and desires about health when searching for health-related keywords
      on search engines. Data are also generated by the use of mobile phone
      applications that track users' health behaviors (e.g., eating and exercise
      habits) as well as give medical advice. The data generated through these
      applications are mined and repackaged by surveillance systems developed by
      academics, companies, and governments alike to provide insight to patients and
      healthcare providers for medical decisions. Until recently, most Internet
      research in public health has been surveillance focused or monitoring health
      behaviors. Only recently have researchers used and interacted with the crowd to
      ask questions and collect health-related data. In the future, we expect to move
      from this surveillance focus to the "ideal" of Internet-based patient-level
      interventions where healthcare providers help patients change their health
      behaviors. In this article, we highlight the results of our prior research on
      crowd surveillance and make suggestions for the future.

PMID- 25045599
TI  - Prospective Predictors of Body Dissatisfaction in Young Adults: 10-year
      Longitudinal Findings.
AB  - This study identified longitudinal risk factors for body dissatisfaction (BD)
      over a 10-year period from adolescence to young adulthood. Participants (N =
      2134; age at baseline: M =15.0, SD =1.6 years) provided two waves of survey data.
      A 6-step hierarchical linear regression analysis examined the predictive
      contribution of Time 1 BD, weight status, demographics, family and peer
      environmental factors, and psychological factors. Among females, Asian
      race/ethnicity, low self-esteem, greater BD, and higher body mass index during
      adolescence contributed significantly to predicting greater BD at 10-year follow
      up (R2 = 0.27). Among males, demographics (i.e., Asian, other-mixed ethnicity,
      education attainment), depressive symptoms, greater BD, higher body mass index,
      more parent communication, and less peer weight teasing during adolescence
      contributed to BD at follow-up (R2 = 0.27). Findings indicate who may be at
      greatest risk for BD in young adulthood and the types of factors that should be
      addressed during adolescence.

PMID- 25045601
TI  - Afadin controls cadherin cluster stability using clathrin-independent mechanism.
AB  - Afadin is an actin-binding protein that interacts with the intracellular region
      of the transmembrane proteins, nectins. In collaboration with other transmembrane
      proteins, cadherins, nectins form adherens junctions, a major type of cell-cell
      adhesive structures in the multicellular organisms. To elucidate the afadin
      function, we studied adherens junction defects induced by afadin depletion in
      epithelial A431 cells. We have found that the cells lacking afadin exhibit no
      abnormalities in morphology or in general dynamics of adherens junctions in the
      confluent cell cultures. The only observed difference is a slight increase in the
      rate of cadherin turnover in these junctions. However, afadin depletion strongly
      affects the assembly of new adherens junctions immediately after two cells touch
      one another: initiation of new junctions is significantly delayed, the growth of
      the nascent junctions stagnates, and their lifetime shortens. As a result, the
      afadin-depleted cells need much more time to establish the mature junctional
      structures. This defect is not caused by the clathrin-dependent endocytosis of
      cadherin clusters that was monitored using live-cell imaging of A431 cells co
      expressing GFP-tagged E-cadherin and mCherry-tagged clathrin light chain. Taken
      together our data show that afadin reinforces adherens junctions and that this
      process is crucial for the fast formation of adherens junctions at the sites of
      new cell-cell contacts. 

PMID- 25045602
TI  - Common gas phase molecules from fungi affect seed germination and plant health in
      Arabidopsis thaliana.
AB  - Fungal volatile organic compounds (VOCs) play important ecophysiological roles in
      mediating inter-kingdom signaling with arthropods but less is known about their
      interactions with plants. In this study, Arabidopsis thaliana was used as a model
      in order to test the physiological effects of 23 common vapor-phase fungal VOCs
      that included alcohols, aldehydes, ketones, and other chemical classes. After
      exposure to a shared atmosphere with the 23 individual VOCs for 72 hrs, seeds
      were assayed for rate of germination and seedling formation; vegetative plants
      were assayed for fresh weight and chlorophyll concentration. All but five of the
      VOCs tested (1-decene, 2-n-heptylfuran, nonanal, geosmin and -limonene) had a
      significant effect in inhibiting either germination, seedling formation or both.
      Seedling formation was entirely inhibited by exposure to 1-octen-3-one, 2
      ethylhexanal, 3-methylbutanal, and butanal. As assayed by a combination of fresh
      weight and chlorophyll concentration, 2-ethylhexanal had a negative impact on two
      week-old vegetative plants. Three other compounds (1-octen-3-ol, 2-ethylhexanal,
      and 2-heptylfuran) decreased fresh weight alone. Most of the VOCs tested did not
      change the fresh weight or chlorophyll concentration of vegetative plants. In
      summary, when tested as single compounds, fungal VOCs affected A. thaliana in
      positive, negative or neutral ways. 

PMID- 25045604
TI  - Exploiting Thread-Level and Instruction-Level Parallelism to Cluster Mass
      Spectrometry Data using Multicore Architectures.
AB  - Modern mass spectrometers can produce large numbers of peptide spectra from
      complex biological samples in a short time. A substantial amount of redundancy is
      observed in these data sets from peptides that may get selected multiple times in
      Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) experiments. A large
      number of spectra do not get mapped to specific peptide sequences due to low
      signal-to-noise (S/N) ratio of the spectra from these machines. Clustering is one
      way to mitigate the problems of these complex mass spectrometry data sets.
      Recently we presented a graph theoretic framework, known as CAMS, for clustering
      of large-scale mass spectrometry data. CAMS utilized a novel metric to exploit
      the spatial patterns in the mass spectrometry peaks which allowed highly accurate
      clustering results. However, comparison of each spectrum with every other
      spectrum makes the clustering problem computationally inefficient. In this paper
      we present a parallel algorithm, called P-CAMS, that uses thread-level and
      instruction-level parallelism on multicore architectures to substantially
      decrease running times. P-CAMS relies on intelligent matrix completion to reduce
      the number of comparisons, threads to run on each core and Single Instruction
      Multiple Data (SIMD) paradigm inside each thread to exploit massive parallelism
      on multicore architectures. A carefully crafted load-balanced scheme that uses
      spatial locations of the mass spectrometry peaks mapped to nearest level cache
      and core allows super-linear speedups. We study the scalability of the algorithm
      with a wide variety of mass spectrometry data and variation in architecture
      specific parameters. The results show that SIMD style data parallelism combined
      with thread-level parallelism for multicore architectures is a powerful
      combination that allows substantial reduction in runtimes even for all-to-all
      comparison algorithms. The quality assessment is performed using real-world data
      set and is shown to be consistent with the serial version of the same algorithm.

PMID- 25045600
TI  - Structure and function of the ependymal barrier and diseases associated with
      ependyma disruption.
AB  - The neuroepithelium is a germinal epithelium containing progenitor cells that
      produce almost all of the central nervous system cells, including the ependyma.
      The neuroepithelium and ependyma constitute barriers containing polarized cells
      covering the embryonic or mature brain ventricles, respectively; therefore, they
      separate the cerebrospinal fluid that fills cavities from the developing or
      mature brain parenchyma. As barriers, the neuroepithelium and ependyma play key
      roles in the central nervous system development processes and physiology. These
      roles depend on mechanisms related to cell polarity, sensory primary cilia,
      motile cilia, tight junctions, adherens junctions and gap junctions, machinery
      for endocytosis and molecule secretion, and water channels. Here, the role of
      both barriers related to the development of diseases, such as neural tube
      defects, ciliary dyskinesia, and hydrocephalus, is reviewed. 

PMID- 25045603
TI  - Evaluation of [(11)C]oseltamivir uptake into the brain during immune activation
      by systemic polyinosine-polycytidylic acid injection: a quantitative PET study
      using juvenile monkey models of viral infection.
AB  - BACKGROUND: Abnormal behaviors of young patients after taking the anti-influenza
      agent oseltamivir (Tamiflu(r), F. Hoffmann-La Roche, Ltd., Basel, Switzerland)
      have been suspected as neuropsychiatric adverse events (NPAEs). Immune response
      to viral infection is suspected to cause elevation of drug concentration in the
      brain of adolescents. In the present study, the effect of innate immune
      activation on the brain uptake of [(11)C]oseltamivir was quantitatively evaluated
      in juvenile monkeys. METHODS: Three 2-year-old monkeys underwent positron
      emission tomography (PET) scans at baseline and immune-activated conditions. Both
      scans were conducted under pre-dosing of clinically relevant oseltamivir. The
      immune activation condition was induced by the intravenous administration of
      polyinosine-polycytidylic acid (poly I:C). Dynamic [(11)C]oseltamivir PET scan
      and serial arterial blood sampling were performed to obtain [(11)C]oseltamivir
      kinetics. Brain uptake of [(11)C]oseltamivr was evaluated by its normalized brain
      concentration, brain-to-plasma concentration ratio, and plasma-to-brain transfer
      rate. Plasma pro-inflammatory cytokine levels were also measured. RESULTS: Plasma
      interleukin-6 was elevated after intravenous administration of poly I:C in all
      monkeys. Brain radioactivity was uniform both at baseline and under poly I:C
      treatment. The mean brain concentrations of [(11)C]oseltamivir were 0.0033 and
      0.0035% ID/cm(3) * kg, the mean brain-to-plasma concentration ratios were 0.58
      and 0.65, and the plasma-to-brain transfer rates were 0.0047 and 0.0051
      mL/min/cm(3) for baseline and poly I:C treatment, respectively. Although these
      parameters were slightly changed by immune activation, the change was not
      notable. CONCLUSIONS: The brain uptake of [(11)C]oseltamivir was unchanged by
      poly I:C treatment in juvenile monkeys. This study demonstrated that the innate
      immune response similar to the immune activation of influenza would not notably
      change the brain concentration of oseltamivir in juvenile monkeys.

PMID- 25045605
TI  - The surprising influence of family history to type 2 diabetes on anaerobic
      performance of young male elite athletes.
AB  - AIMS/HYPOTHESIS: It is known that family history to type 2 diabetes induces
      anthropometric changes in various populations. Regular physical activity can
      induce adaptations in these subjects regularizing body composition and
      anthropometric parameters. The aim of this study is therefore to understand if
      family history to type 2 diabetes affects anaerobic performance in young male
      elite athletes. METHODS: Forty six young male elite athletes were tested. Thirty
      three without family history to type 2 diabetes (FH-) and thirteen with family
      history to type 2 diabetes (FH+). Anthropometric parameters, body composition,
      physiological parameters and athletic performance were assessed. RESULTS: Weight
      (p 0,0050), BMI (p 0,0019), waist circumference (p 0,0090), hips circumference (p
      0,0490) and WHR (p 0,0339) were different between the two groups, showing greater
      values for the FH + subjects. Body composition showed lower FM and higher FFM
      percentages for the FH + group compared to the FH-. Anaerobic performance tests
      showed differences between the groups highlighting that the FH + group had higher
      anaerobic performance values (Wingate test for FH + 512,77 +/- 107,93 W vs
      Wingate test for FH- 447,94 +/- 56,95 W). CONCLUSIONS/INTERPRETATION: The elite
      athletes with FH + showed better anaerobic performances and a higher body mass.
      At this stage we cannot generalise, but in a sample of athletes we tested, all
      who were with FH + showed both interesting and unexpected results; if confirmed,
      this evidence may represent a remarkable knowledge for fitness coaches and
      professionals who are daily dealing with track and field athletes and their
      performances.

PMID- 25045607
TI  - Trigonometrically-fitted second derivative method for oscillatory problems.
AB  - ABSTRACT: A continuous Trigonometrically-fitted Second Derivative Method (CTSDM)
      whose coefficients depend on the frequency and stepsize is constructed using
      trigonometric basis functions. A discrete Trigonometrically-fitted second
      derivative method (TSDM) is recovered from the CTSDM as a by-product and applied
      to solve initial value problems (IVPs) with oscillating solutions. We discuss the
      stability properties of the TSDM and present numerical experiments to demonstrate
      the efficiency of the method. AMS SUBJECT CLASSIFICATION: 65L05; 65L06.

PMID- 25045606
TI  - Computerized database management system for breast cancer patients.
AB  - Data analysis based on breast cancer risk factors such as age, race,
      breastfeeding, hormone replacement therapy, family history, and obesity was
      conducted on breast cancer patients using a new enhanced computerized database
      management system. My Structural Query Language (MySQL) is selected as the
      application for database management system to store the patient data collected
      from hospitals in Malaysia. An automatic calculation tool is embedded in this
      system to assist the data analysis. The results are plotted automatically and a
      user-friendly graphical user interface is developed that can control the MySQL
      database. Case studies show breast cancer incidence rate is highest among Malay
      women, followed by Chinese and Indian. The peak age for breast cancer incidence
      is from 50 to 59 years old. Results suggest that the chance of developing breast
      cancer is increased in older women, and reduced with breastfeeding practice. The
      weight status might affect the breast cancer risk differently. Additional studies
      are needed to confirm these findings. 

PMID- 25045608
TI  - Anatomical variations of the axilla.
AB  - PURPOSE: The present study aimed to measure the thickness of the subcutaneous
      adipose tissue (SAT) at the site of the surgical incision for axillary lymph node
      dissection (ALND) and to record potential anatomical variations in the medial
      cutaneous nerve of the arm (MCNA), the intercostobrachial nerve (ICBN), the
      lateral thoracic vein (LTV), the lateral thoracic artery (LTA) and the pectoral
      muscle pedicle (PMP), considering that some details of the anatomy of these
      structures within the axilla are still unclear. METHODS: A prospective study was
      conducted in 100 consecutive patients with breast cancer who underwent ALND as
      part of surgical treatment. The anatomy of the dissected axilla was video
      recorded. RESULTS: The SAT thickness ranged from 8 mm to 60 mm, with an average
      thickness of 25.9 mm. A positive correlation was observed between the SAT
      thickness and the body mass index (BMI) of the evaluated patients (r = 0.68; p <
      0.0001). The MCNA was the anatomical structure that was least commonly observed
      in the axilla (22% of cases), while the PMP was the most constant element,
      identified in 100% of cases. All of the studied anatomical structures observed
      within the axilla showed variation in at least one of the aspects analyzed, i.e.,
      the point of entry and exit, path, number and location of divisions or branches.
      CONCLUSION: The present study demonstrated wide variation in thickness of the SAT
      overlying the axilla and identified the existence of broad normative anatomical
      variation of the axilla.

PMID- 25045609
TI  - Effect of gibberellic acid (GA), indole acetic acid (IAA) and benzylaminopurine
      (BAP) on the synthesis of essential oils and the isomerization of methyl chavicol
      and trans-anethole in Ocimum gratissimum L.
AB  - Basil (O. gratissimum L) is a aromatic and medicinal plant widely used in
      traditional medicine in Morocco. The aim of this work was to study the effect of
      three plant growth regulators gibberellic acid (GA), indole 3-acetic acid (IAA)
      and benzylaminopurine (BAP) on the content and composition of essential oils of
      this plant, especially on the main compound (methyl chavicol) and its isomer (the
      trans-anethole). The results showed a wide variation on yield, content and range
      of the molecule constituent of oil, with a balance of appearances and/or
      disappearances of a few molecules. GA caused a slight decrease in the oil yield
      (0.2%), but it increased the diversity of compounds (17 molecules) with the
      appearance of four new compounds (naphthalene, camphor, germacrene-D, and ledene)
      and disappearance of (beta cedrene, azulene). This variation also caused a very
      important decrease in the main compound (methyl chavicol) and increases its
      isomer (trans-anethole). IAA and BAP caused an increase in the yield of essential
      oil (0.30% and 0.32% respectively) without much influence on the main compounds,
      but with some change in the composition such as the appearance of (germacrene-D)
      and the disappearance of (aristolene). 

PMID- 25045610
TI  - Regional distribution of mercury in sediments of the main rivers of French Guiana
      (Amazonian basin).
AB  - Use of mercury (Hg) for gold-mining in French Guiana (up until 2006) as well as
      the presence of naturally high background levels in soils, has led to locally
      high concentrations in soils and sediments. The present study maps the levels of
      Hg concentrations in river sediments from five main rivers of French Guiana
      (Approuague River, Comte River, Mana River, Maroni River and Oyapock River) and
      their tributaries, covering more than 5 450 km of river with 1 211 sampling
      points. The maximum geological background Hg concentration, estimated from 241
      non-gold-mined streams across French Guiana was 150 ng g(-1). Significant
      differences were measured between the five main rivers as well as between all
      gold-mining and pristine areas, giving representative data of the Hg increase due
      to past gold-mining activities. These results give a unique large scale vision of
      Hg contamination in river sediments of French Guiana and provide fundamental data
      on Hg distribution in pristine and gold-mined areas. 

PMID- 25045611
TI  - Health resource utilization associated with skeletal-related events in patients
      with advanced breast cancer: results from a prospective, multinational
      observational study.
AB  - Patients with breast cancer and bone metastases often experience skeletal
      complications (skeletal-related events [SREs]: pathologic fracture, radiation to
      bone, surgery to bone or spinal cord compression). Prospective data on the health
      resource burden of SREs are needed for planning healthcare requirements and
      estimating the value of new treatments, but limited data are available. This
      prospective, observational study collected health resource utilization (HRU) data
      independently attributed to SREs by investigators. Eligible patients had bone
      metastases secondary to breast cancer, life expectancy >=6 months, Eastern
      Cooperative Oncology Group (ECOG) performance status <=2, and at least one SRE in
      the 97 days before enrollment. Data, collected retrospectively for 97 days before
      enrollment and prospectively for 18-21 months, included number and duration of
      inpatient stays, outpatient visits, emergency room visits and procedures.
      Altogether, 223 patients were enrolled from Germany, Italy, Spain and the UK. Of
      the 457 SREs, 118 (25.8%) were associated with inpatient stays. The mean duration
      of stay was 19.5 (standard deviation [SD] 19.2) days per SRE (based on 117 SREs).
      Surgery to bone and spinal cord compression were the SREs most likely to require
      inpatient stays (77.8% and 57.9% of SREs, respectively), while radiation to bone
      was the least likely (9.7%). Spinal cord compression required the longest
      inpatient stay per event (34.2 [SD 30.2] days) and radiation to bone the shortest
      (14.3 [SD 10.2] days). Overall, 342 SREs (74.8%) required an outpatient visit,
      with radiation to bone the most likely (85.7%), and surgery to bone the least
      likely (42.6%). Radiation to bone was also associated with the greatest number of
      outpatient visits per event (6.8 [SD 6.7] visits). All SREs were associated with
      substantial HRU therefore, preventing SREs in patients with breast cancer may
      reduce the burden imposed on healthcare systems. 

PMID- 25045612
TI  - Biological dosimetry for breast cancer radiotherapy: a comparison of external
      beam and intraoperative radiotherapy.
AB  - PURPOSE: External beam radiotherapy (EBRT) is the gold standard adjuvant
      treatment after breast conserving surgery although a recent phase 3 trial has
      shown the non-inferiority of intraoperative radiotherapy (IORT). Radiation
      exposure of the heart and cardiac vessels causes an increase in morbidity and
      mortality following EBRT for breast cancer. We have used gamma-H2AX foci
      formation in peripheral blood lymphocytes as a surrogate marker of dose delivered
      to the heart and great vessels and have assessed the feasibility of using this
      technique for biological dosimetry. METHODS: 34 patients were recruited, having
      either EBRT or IORT as part of a randomised controlled trial (TARGIT). Blood
      samples were taken prior to and after first fraction of radiotherapy, and the
      gamma-H2AX biomarker then quantified. RESULTS: Data were available for 31
      patients. Following TARGIT-IORT there was an increase of 0.203 foci per cell
      (range -1.436 to 1.275) compared with 0.935 foci per cell (range -0.679 to 2.216)
      in the EBRT group; this difference was highly significant (p = 0.009). As TARGIT
      IORT treatment is completed with a single fraction, whilst EBRT requires at least
      15 fractions, the actual difference is estimated to be many times more.
      CONCLUSIONS: These data show a significantly greater change in gamma-H2AX foci
      number per cell following one fraction of EBRT compared to TARGIT-IORT. This is
      the first study to demonstrate this effect using a biomarker and demonstrates a
      proof of concept methodology for similar applications.

PMID- 25045614
TI  - Sensitivity and specificity of PET/CT regarding the detection of lymph node
      metastases in prostate cancer recurrence.
AB  - BACKGROUND: The aim of the study is to assess the efficacy of choline PET/CT
      regarding the detection of lymph node (LN) metastases in recurrent prostate
      cancer (PCa). METHODS: 49 patients with a biochemical recurrence of PCa (PSA >0.2
      ng/ml) were included in the study. All patients were selected for further
      diagnostics with a choline-PET/CT. All patients underwent salvage extended
      lymphadenectomy. The PET/CT result and the histological findings were analyzed
      regarding the specificity and sensitivity and with respect to the localization of
      the metastases. The detection rate of LN metastases was analyzed with respect to
      interdependencies between the pre-PET/CT PSA-value as well as the role of prior
      ADT. RESULTS: 41 out of 49 (83.6%) patients showed positive PET/CT results.
      Positive LNs were found in 27 out of 49 patients (55.1%). 48.9% of the PET-CT
      findings proved true positive, 36.7% were found to be false positive. 8.1% proved
      true negative and 8.1% false negative. This results in a specificity of 22.7% and
      a sensitivity of 85.1%. Out of the true positive PET/CT scans, 61.9% were not
      congruent regarding the localization of positive LNs. In patients with PSA
      [greater than or equal to] 5 ng/ml, the sensitivity of the PET/CT result was
      93.7%, while specificity was 0%. In 24 patients who underwent ADT prior to the
      PET/CT diagnostics, the sensitivity was 84.6% and specificity 9.0%. CONCLUSIONS:
      The reliability of PET/CT imaging for detection of LN metastases is limited by a
      high false-positive rate. The influence of ADT further diminishes the PET/CT
      reliability. Sensitivity of the PET/CT is highest in patients with a PSA of
      [greater than or equal to] 5 ng/ml. Based on our results, we propose the
      following conclusions: 1. There is no well-established diagnostic alternative to
      Choline-PET/CT Scan. Therefore this method may continue to be performed in
      patients with BCR. 2. It is not sufficient to remove only those LNs that show up
      in the PET/CT. 3. Salvage extended lymphadenectomy should follow a predefined
      template (e.g. the "Kiel template") and not just the PET/CT scan results.

PMID- 25045613
TI  - Epidemiology of dementia in Central Africa (EPIDEMCA): protocol for a multicentre
      population-based study in rural and urban areas of the Central African Republic
      and the Republic of Congo.
AB  - BACKGROUND: The worldwide population is ageing and the proportion of elderly aged
      60 and over is expected to dramatically rise in Low and Middle Income Countries
      (LMIC). The epidemic of dementia will not spare those countries, where the
      largest increases in numbers of people affected are estimated. Besides, dementia
      is still understudied in sub-Saharan Africa (SSA) compared to other regions. This
      paper describes the protocol for the 'Epidemiology of Dementia in Central Africa'
      population-based study, which aims at estimating the prevalence of dementia in
      two countries of Central Africa and investigating possible risk factors.
      METHODS/DESIGN: A multicenter population-based study was carried out in Central
      African Republic and Republic of Congo between 2011 and 2012 including both urban
      and rural sites in each country. Around 2000 participants aged >=65 years old
      were interviewed in total using the Community Screening Interview for Dementia
      (CSI-D), the GMS-AGECAT and the CERAD's 10-word list. Elderly with low
      performance to the cognitive part of the CSI-D (COGSCORE <= 24.5) were then
      clinically assessed by neurologists and underwent further psychometrical tests.
      DSM-IV and NINCDS-ADRDA criteria were required for dementia and Alzheimer's
      disease (AD) diagnoses respectively. The algorithmic 10/66 dementia diagnosis was
      also determined. Petersen's criteria were required for the diagnosis of Mild
      Cognitive Impairment. Sociodemographic, and environmental factors including
      vascular, nutritional, biological, psychosocial and lifestyle factors were
      collected in each setting in order to investigate factors associated with
      dementia. Blood sampling was realized to investigate genetic variations that
      could modify the risk of dementia. DISCUSSION: For now, no large epidemiological
      study has been undertaken to compare the prevalence of dementia in both rural and
      urban areas within SSA countries. This programme will provide further evidence
      regarding the prevalence of dementia in SSA, and also the possible rural/urban
      disparities existing with associated factors. Furthermore, the genetics of AD in
      those populations will be addressed.

PMID- 25045615
TI  - Primary diffuse large B-cell lymphoma of the bone: bendamustine and rituximab are
      able to overcome resistant disease.
AB  - Primary bone lymphoma (PBL) is a rare disease for which specific therapeutic
      guidelines have not yet been established. Due to common appearance in the elderly
      and recurring relapses, new treatments are required. We report the case of
      multiple relapsed aggressive PBL effectively treated using Bendamustine and
      Rituximab. A 78-year-old male patient presented with a painful mass in the left
      arm. Computed tomography (CT) showed a pathological tissue in the humerus
      diaphysis infiltrating the muscle, confirmed by positron emission tomography
      (PET) scan. Indeed, PET excluded pathological local lymph node involvement.
      Biopsy of the humerus revealed the presence of diffuse large B cell lymphoma.
      Recommended treatments for PBL were used, but relapses after an initial complete
      response occurred. Following the positive experience of Vacirca et al. the
      patient underwent Bendamustin 90 mg/mq gg1-2 q28 plus Rituximab 375 mg/mq q28
      (BR). Herein we report the first experience of BR combination in PBL and it
      proved to be an efficacious and safe salvage therapy in relapsed/refractory PBL. 

PMID- 25045616
TI  - Evaluation of mycotoxin sequestering agents for aflatoxin and deoxynivalenol: an
      in vitro approach.
AB  - An experiment was conducted to determine the efficacy of mycotoxin sequestering
      agents for binding or degrading aflatoxin B1 (AFB1) and deoxynivalenol (DON) by
      an in vitro method. Ten toxin binder products including 5 bentonite clays
      (bentonite A, B, C, D, and E), 2 cellulose products (cellulose A and B), a yeast
      cell wall, an activated charcoal, and a mixture product containing minerals,
      microorganisms, and phytogenic substances were used in this experiment. An in
      vitro procedure was used to mimic the digestive process in pigs. The binding
      ability for AFB1 of the cellulose products was less compared with the values of
      other sequestering products (p < 0.05). The percent adsorption of AFB1 by
      bentonite clays, cellulose products, yeast cell wall product, activated charcoal
      product, and the mixture product were 92.5 (average of 5 bentonite products), 
      13.5 (average of 2 cellulose products), 92.7, 100.2, and 96.6, respectively. The
      respective values for DON were 3.24, 11.6, 22.9, 14.4, and 4.3. In conclusion,
      most toxin sequestering agents used in the present study had potential to bind
      AFB1 rather than DON based on the in vitro study which simulated the pH condition
      of the gastrointestinal tract of pigs. 

PMID- 25045617
TI  - Bone marrow fibrosis as a feature of systemic lupus erythematosus: a case report
      and literature review.
AB  - INTRODUCTION: Peripheral cytopenias are common in systemic lupus erythematosus
      (SLE), but bone marrow involvement is rarely reported. Myelofibrosis is a rare
      disorder characterized by reticulin fibrosis of the bone marrow, which usually
      occurs in response to clonal proliferation of hematopoietic stem cells in
      myeloproliferative disorders. However, bone marrow fibrosis has also been
      described in association with auto-immune diseases, especially SLE. METHOD: We
      will report here a new case of bone marrow fibrosis associated with SLE. We also
      reviewed the 27 cases published in the English language literature, and will
      discuss the clinical presentation, outcome, treatment, and pathophysiology of
      bone marrow fibrosis occurring in association with SLE. RESULTS: Over one half of
      patients were diagnosed concomitantly with bone marrow fibrosis and SLE.
      Epidemiological, clinical and biological features of lupus were unremarkable.
      Except for the presence of reticulin fibrosis, the findings from the bone marrow
      biopsies proved highly variable. Overall mortality was about 14% but
      corticosteroid-based therapy lead to clinical improvement and reverted bone
      marrow fibrosis in most cases. Data on the usefulness of other immunomodulatory
      therapies are inconclusive. CONCLUSIONS: SLE may be complicated by bone marrow
      involvement, of a likely autoimmune origin. Bone marrow fibrosis occurring with
      SLE is probably similar to "primary autoimmune myelofibrosis" and may respond to
      steroid and immunomodulatory therapies. Further studies with standardised
      proofreading of bone marrow aspirations and biopsies are needed to delineate the
      clinical and biological features of this rare complication of SLE.

PMID- 25045618
TI  - Mechanisms of Liver Injury in Non-Alcoholic Steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) is a disorder marked by alterations in
      hepatic lipid homeostasis as well as liver injury in the form of cell death,
      inflammation and fibrosis. Research into the pathophysiology of NASH is dynamic.
      New concepts from the fields of cell biology, microbiology, immunology and
      genetics are being tested for their applicability to NASH; discoveries in each of
      these areas are enriching our understanding of this complex disease. This review
      summarizes how recent developments from the bench and bedside are merging with
      more traditional concepts to reshape our view of NASH pathogenesis. Highlights
      include human studies that emphasize the role of de novo lipogenesis in NASH and
      experimental work uncovering a role for the inflammasome in NASH. Genetic
      predispositions to NASH are being clarified, and intestinal microbiome is
      emerging as a determinant of fatty liver. These unique ideas are now taking their
      place within an integrated picture of NASH pathogenesis.

PMID- 25045621
TI  - After 40 years, new medicine for combating TB.

PMID- 25045619
TI  - The Genetics, Neurogenetics and Pharmacogenetics of Addiction.
AB  - Addictions are prevalent psychiatric disorders that confer remarkable personal
      and social burden. Despite substantial evidence for their moderate, yet robust,
      heritability (approx. 50%), specific genetic mechanisms underlying their
      development and maintenance remain unclear. The goal of this selective review is
      to highlight progress in unveiling the genetic underpinnings of addiction. First,
      we revisit the basis for heritable variation in addiction before reviewing the
      most replicable candidate gene findings and emerging signals from genomewide
      association studies for alcohol, nicotine and cannabis addictions. Second, we
      survey the modest but growing field of neurogenetics examining how genetic
      variation influences corticostriatal structure, function, and connectivity to
      identify neural mechanisms that may underlie associations between genetic
      variation and addiction. Third, we outline how extant genomic findings are being
      used to develop and refine pharmacotherapies. Finally, as sample sizes for
      genetically informed studies of addiction approach critical mass, we posit five
      exciting possibilities that may propel further discovery (improved phenotyping,
      rare variant discovery, gene-environment interplay, epigenetics, and novel
      neuroimaging designs).

PMID- 25045622
TI  - Genome-wide transcriptomic alterations induced by ethanol treatment in human
      dental pulp stem cells (DPSCs).
AB  - Human dental pulp stem cells (DPSCs) isolated from adult dental pulp are
      multipotent mesenchymal stem cells that can be directed to differentiate into
      osteogenic/odontogenic cells and also trans-differentiate into neuronal cells.
      The utility of DPSC has been explored in odontogenic differentiation for tooth
      regeneration. Alcohol abuse appears to lead to periodontal disease, tooth decay
      and mouth sores that are potentially precancerous. Persons who abuse alcohol are
      at high risk of having seriously deteriorated teeth, gums and compromised oral
      health in general. It is currently unknown if alcohol exposure has any impact on
      adult stem cell maintenance, stem cell fate determination and plasticity, and
      stem cell niche environment. Here we provide detailed experimental methods,
      analysis and information associated with our data deposited into Gene Expression
      Omnibus (GEO) under GSE57255. Our data provide transcriptomic changes that are
      occurring by EtOH treatment of DPSCs at 24-hour and 48-hour time point.

PMID- 25045620
TI  - Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal
      Aging and Alzheimer's Disease.
AB  - Preclinical detection of Alzheimer disease is critical to determining at-risk
      individuals in order to improve patient and caregiver planning for their futures
      and to identify individuals likely to benefit from treatment as advances in
      therapeutics develop over time. Identification of olfactory dysfunction at the
      preclinical and early stages of the disease is a potentially useful method to
      accomplish these goals. We first review basic olfactory circuitry. We then
      evaluate the evidence of pathophysiological change in the olfactory processing
      pathways during aging and Alzheimer disease in both human and animal models. We
      also review olfactory behavioral studies during these processes in both types of
      models. In doing so, we suggest hypotheses about the localization and mechanisms
      of olfactory dysfunction and identify important avenues for future work.

PMID- 25045623
TI  - Participant retention in an automated online monthly depression rescreening
      program: patterns and predictors.
AB  - Internet-based mental health resources often suffer from low engagement and
      retention. An increased understanding of engagement and attrition is needed to
      realize the potential of such resources. In this study, 45,142 individuals were
      screened for depression by an automated online screener, with 2,539 enrolling in
      a year-long monthly rescreening study; they received a single monthly reminder
      email to rescreen their mood. We found that, even with such a minimal cohort
      maintenance strategy, a third of the participants completed 1 or more follow-ups,
      and 22% completed 2 or more follow-ups. Furthermore, completion of earlier follow
      ups was highly predictive of future completions. We also found a number of
      participant characteristics (e.g., current depression status, previous depression
      treatment seeking, education level) predicted follow-up rates, singly or in
      interactions.

PMID- 25045624
TI  - Facebook Recruitment of Young Adult Smokers for a Cessation Trial: Methods,
      Metrics, and Lessons Learned.
AB  - Further understanding is needed of the functionalities and efficiency of social
      media for health intervention research recruitment. Facebook was examined as a
      mechanism to recruit young adults for a smoking cessation intervention. An ad
      campaign targeting young adult smokers tested specific messaging based on market
      theory and successful strategies used to recruit smokers in previous clinical
      trials (i.e. informative, call to action, scarcity, social norms), previously
      successful ads, and general messaging. Images were selected to target smokers
      (e.g., lit cigarette), appeal to the target age, vary demographically, and vary
      graphically (cartoon, photo, logo). Facebook's Ads Manager was used over 7 weeks
      (6/10/13 - 7/29/13), targeted by age (18-25), location (U.S.), and language
      (English), and employed multiple ad types (newsfeed, standard, promoted posts,
      sponsored stories) and keywords. Ads linked to the online screening survey or
      study Facebook page. The 36 different ads generated 3,198,373 impressions, 5,895
      unique clicks, at an overall cost of $2,024 ($0.34/click). Images of smoking and
      newsfeed ads had the greatest reach and clicks at the lowest cost. Of 5,895
      unique clicks, 586 (10%) were study eligible and 230 (39%) consented. Advertising
      costs averaged $8.80 per eligible, consented participant. The final study sample
      (n=79) was largely Caucasian (77%) and male (69%), averaging 11 cigarettes/day
      (SD=8.3) and 2.7 years smoking (SD=0.7). Facebook is a useful, cost-effective
      recruitment source for young adult smokers. Ads posted via newsfeed posts were
      particularly successful, likely because they were viewable via mobile phone.
      Efforts to engage more ethnic minorities, young women, and smokers motivated to
      quit are needed.

PMID- 25045625
TI  - The Course and Correlates of Everyday Functioning in Schizophrenia.
AB  - Previously institutionalized older patients with schizophrenia show changes in
      cognitive and functional capacity over time. This study examined changes in real
      world functioning in a sample of people with schizophrenia who varied in their
      history of long-term institutionalization and related changes in real world
      functioning to changes in cognition and functional capacity over the follow-up
      period. Older patients with schizophrenia (n=111) were examined with assessments
      of cognitive functioning, functional capacity, clinical symptoms, and everyday
      functioning. They were then followed up to 45 months and examined up to two
      times. Mixed-model regression was used to examine changes in real-world
      functioning in social, everyday living, and vocational domains over the follow-up
      period and identify potential predictors of change. Everyday functioning worsened
      over time in all three domains. Although length of longest hospitalization
      predicted worsening, this influence was eliminated when the course of functional
      capacity was used to predict the course of everyday functioning. For both
      vocational and everyday living domains, as well as the composite score on
      functional status, worsening in performance based measures of everyday
      functioning and social competence predicted worsening in real world functioning.
      Changes in negative symptoms further predicted worsening in the everyday living
      domain. Worsening in everyday functioning is found in people with schizophrenia
      and those with a history of greater chronicity and severity of illness seem more
      affected. These influences seem to be expressed through worsening in the ability
      to perform everyday functional skills. Potential causes of these changes and
      implications for reducing these impairments are discussed.

PMID- 25045627
TI  - In vitro maturation of human oocytes: Its role in infertility treatment and new
      possibilities.
AB  - IVM refers to the maturation of immature oocytes in culture after their recovery
      from small antral follicles at the stage prior to selection and dominance. IVM
      requires little or no FSH in vivo and has been proposed as an alternative to
      conventional IVF, since it reduces the primary adverse effects caused by
      controlled ovarian stimulation, including the ovarian hyperstimulation syndrome.
      Moreover, IVM is a promising option for cases for which no standard protocol is
      suitable, such as FSH resistance, contraindications for ovarian stimulatory
      drugs, and the need for urgent fertility preservation. Recently, IVM has been
      used in women with regular cycles and normal ovaries. However, the pregnancy rate
      following IVM is suboptimal compared with that of conventional IVF, indicating
      that further studies to optimize the protocol and the culture conditions are
      warranted. 

PMID- 25045626
TI  - Androgen receptor gene mutation, rearrangement, polymorphism.
AB  - Genetic aberrations of the androgen receptor (AR) caused by mutations,
      rearrangements, and polymorphisms result in a mutant receptor that has varied
      functions compared to wild type AR. To date, over 1,000 mutations have been
      reported in the AR with most of these being associated with androgen
      insensitivity syndrome (AIS). While mutations of AR associated with prostate
      cancer occur less often in early stage localized disease, mutations in castration
      resistant prostate cancer (CRPC) patients treated with anti-androgens occur more
      frequently with 10-30% of these patients having some form of mutation in the AR.
      Resistance to anti-androgen therapy usually results from gain-of-function
      mutations in the LBD such as is seen with bicalutamide and more recently with
      enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations
      arising from drug resistance to anti-androgens and other small molecule
      pharmacological agents.

PMID- 25045628
TI  - Maternal effect genes: Findings and effects on mouse embryo development.
AB  - Stored maternal factors in oocytes regulate oocyte differentiation into embryos
      during early embryonic development. Before zygotic gene activation (ZGA), these
      early embryos are mainly dependent on maternal factors for survival, such as
      macromolecules and subcellular organelles in oocytes. The genes encoding these
      essential maternal products are referred to as maternal effect genes (MEGs). MEGs
      accumulate maternal factors during oogenesis and enable ZGA, progression of early
      embryo development, and the initial establishment of embryonic cell lineages.
      Disruption of MEGs results in defective embryogenesis. Despite their important
      functions, only a few mammalian MEGs have been identified. In this review we
      summarize the roles of known MEGs in mouse fertility, with a particular emphasis
      on oocytes and early embryonic development. An increased knowledge of the working
      mechanism of MEGs could ultimately provide a means to regulate oocyte maturation
      and subsequent early embryonic development. 

PMID- 25045629
TI  - Is catechol-o-methyltransferase gene polymorphism a risk factor in the
      development of premenstrual syndrome?
AB  - OBJECTIVE: The objective of this study was to investigate whether there was a
      correlation between catechol-o-methyltransferase (COMT) gene polymorphism, which
      is believed to play a role in the etiology of psychotic disorders, and
      premenstrual syndrome (PMS). METHODS: Fifty-three women with regular menstrual
      cycles, aged between 18 and 46 years and diagnosed with PMS according to the
      American Congress of Obstetrics and Gynecology criteria were included in this
      study as the study group, and 53 healthy women having no health problems were
      selected as the controls. Venous blood was collected from all patients included
      in the study and kept at -18C prior to analysis. RESULTS: There was no
      significant difference between the groups in terms of demographic features such
      as age, body mass index, number of pregnancies, parity, and number of children.
      No statistically significant difference was observed in terms of COMT gene
      polymorphism (p=0.61) between women in the PMS and the control groups. However, a
      significant difference was found between arthralgia, which is an indicator of
      PMS, and low-enzyme activity COMT gene (Met/Met) polymorphism (p=0.04).
      CONCLUSION: These results suggested that there was no significant relationship
      between PMS and COMT gene polymorphism. Since we could not find a direct
      correlation between the COMT gene polymorphism and PMS, further studies including
      alternative neurotransmitter pathways are needed to find an effective treatment
      for this disease.

PMID- 25045630
TI  - The effect of various assisted hatching techniques on the mouse early embryo
      development.
AB  - OBJECTIVE: In search of an ideal method of assisted hatching (AH), we compared
      the effects of conventional micropipette-AH and laser-AH on the blastocyst
      formation rate (BFR) and blastocyst cell numbers. METHODS: Four- to five-week-old
      ICR female mice were paired with male mice after superovulation using Pregnant
      mare's serum gonadotropin (PMSG) and hCG. The two-cell embryos were flushed from
      the oviducts of female mice. The retrieved two-cell embryos underwent one of five
      AH procedures: single mechanical assisted hatching (sMAH); cross mechanical
      assisted hatching (cMAH); single laser assisted hatching (sLAH); quarter laser
      assisted hatching (qLAH); and quarter laser zona thinning assisted hatching (qLZT
      AH). After 72 hours incubation, double immunofluorescence staining was performed.
      RESULTS: Following a 72 hours incubation, a higher hatching BFR was observed in
      the control, sMAH, cMAH, and sLAH groups, compared to those in the qLAH and qLZT
      AH groups (p<0.05). The hatched BFR was significantly higher in the qLAH and qLZT
      AH groups than in the others (p<0.05 for each group). The inner cell mass (ICM)
      was higher in the control and sMAH group (p<0.05). The trophectoderm cell number
      was higher in the cMAH and qLAH groups (p<0.05). CONCLUSION: Our results showed
      that the hatched BFR was higher in groups exposed the the qLAH and qLZT-AH
      methods compared to groups exposed to other AH methods. In the qLAH group,
      although the total cell number was significantly higher than in controls, the ICM
      ratio was significantly lower in than controls.

PMID- 25045631
TI  - Body composition: A predictive factor of cycle fecundity.
AB  - OBJECTIVE: To study the effect of body composition on reproduction in women with
      unexplained infertility treated with a controlled ovarian hyperstimulation and
      intrauterine insemination programme. METHODS: This prospective observational
      study was conducted on 308 unexplained infertile women who were scheduled for a
      controlled ovarian hyperstimulation and intrauterine insemination programme and
      were grouped as pregnant and non-pregnant. Anthropometric measurements were
      performed using TANITA-420MA before the treatment cycle. Body composition was
      determined using a bioelectrical impedance analysis system. RESULTS: Body fat
      mass was significantly lower in pregnant women than in non-pregnant women
      (15.61+/-3.65 vs.18.78+/-5.97, respectively) (p=0.01). In a multiple regression
      analysis, body fat mass proved to have a stronger association with fecundity than
      the percentage of body fat, body mass index, or the waist/hip ratio (standardized
      regression coefficient>=0.277, t-value>=2.537; p<0.05). The cut-off value of fat
      mass, which was evaluated using the receiver operating characteristics curve, was
      16.65 with a sensitivity of 61.8% and a specificity of 70.2%. Below this cut-off
      value, the odds of the pregnancy occurrence was found to be 2.5 times more
      likely. CONCLUSION: Body fat mass can be predictive for pregnancy in patients
      with unexplained infertility scheduled for a controlled ovarian hyperstimulation
      and intrauterine insemination programme.

PMID- 25045632
TI  - Vitamin D deficiency in women with polycystic ovary syndrome.
AB  - OBJECTIVE: TO INVESTIGATE: the prevalence of vitamin D deficiency in Korean women
      with polycystic ovary syndrome (PCOS), and the relationship between vitamin D
      status and clinical or metabolic features in this group. METHODS: We recruited 38
      women with PCOS using the Rotterdam criteria. A total of 109 premenopausal
      control women were matched with patients based on age and body mass index. Serum
      25-hydroxy vitamin D concentrations less than 20 ng/mL were classified as frank
      vitamin D deficiency. Since vitamin D may play a significant role in metabolic
      disturbances in women with PCOS, correlations between clinical or metabolic
      parameters and vitamin D status were analyzed separately in patients and
      controls. RESULTS: Women with PCOS showed no differences in the level of 25
      hydroxy vitamin D (19.6+/-6.6 ng/mL in patients vs. 20.1+/-7.4 ng/mL in controls,
      respectively, p=0.696) or prevalence of vitamin D deficiency (57.9% in patients
      vs. 56.5% in controls, respectively, p=0.880). In addition, we did not find any
      correlations between serum vitamin D level and clinical or metabolic profiles in
      either PCOS patients or controls. CONCLUSION: Our study found no differences in
      the absolute level of serum vitamin D between PCOS patients and matched controls.
      Prevalence of vitamin D deficiency was equally common among both patients and
      controls. Additionally, we did not find any correlations between serum vitamin D
      level and clinical or metabolic profiles, suggesting that the role of vitamin D
      in the pathogenesis of PCOS is not yet clear.

PMID- 25045633
TI  - Serum luteinizing hormone level and luteinizing hormone/follicle-stimulating
      hormone ratio but not serum anti-Mullerian hormone level is related to ovarian
      volume in Korean women with polycystic ovary syndrome.
AB  - OBJECTIVE: The aim of the present study was to investigate the relationship
      between ovarian follicle count and volume on ultrasonography and serum hormone
      levels including the levels of the anti-Mullerian hormone (AMH) and gonadotropin
      in women with the polycystic ovary syndrome (PCOS). METHODS: A total of 118
      Korean women aged 18-35 years who were newly diagnosed with PCOS at a university
      hospital were included in this study. Serum LH, FSH, and AMH levels were measured
      in the early follicular phase, and the total antral follicle count (TFC) and the
      total ovarian volume (TOV) were assessed by ultrasonography. The correlations
      between serum hormonal parameters and ultrasonography characteristics in women
      with PCOS were evaluated using Pearson's correlation coefficients and a linear
      regression analysis. RESULTS: Serum AMH levels were significantly correlated with
      serum LH levels and LH/FSH ratios, and TFC and TOV were significantly correlated
      with each other on ultrasonography. Serum AMH and LH levels and the LH/FSH ratio
      were significantly correlated with TFC. Statistically significant correlations
      between TOV and the LH level (r=0.208, p=0.024) and the LH/FSH ratio (r=0.237,
      p=0.010) were observed. However, the serum AMH level was not significantly
      correlated with the ovarian volume, and this result did not change after
      adjusting for age and body mass index. CONCLUSION: Serum AMH is not related to
      the ovarian volume in women with PCOS. My results suggest that serum LH level and
      the LH/FSH ratio may be more useful than the serum AMH level for representing the
      status of the ovarian volume in women with PCOS.

PMID- 25045634
TI  - Platelet volume indices in patients with varicocele.
AB  - OBJECTIVE: This study sought to evaluate platelet volume indices (mean platelet
      volume [MPV], platelet distribution width [PDW], and platelet large cell ratio [P
      LCR]) in varicocele patients, and compare it with platelet volume parameters in
      healthy controls. METHODS: This cross-sectional study involved 2 groups: group 1
      included 51 varicocele subjects and group 2 consisted of 50 healthy control
      subjects of similar ages. Peripheral venous blood samples were collected with
      ethylenediaminetetraacetic acid-K2 anticoagulant between 8:30 AM and 10 AM
      following an overnight fast. Platelet volume parameters (MPV, PDW, and P-LCR)
      were measured in both groups within 2 hours of sampling. RESULTS: The mean PDW,
      MPV, and P-LCR were 13.9+/-2.5%, 10.1+/-1.3 fL, and 27.3+/-7.8% in varicocele
      patients, respectively, and were 12.6+/-2.4%, 9.3+/-1.1 fL, and 21.9+/-6.4% in
      the control group, respectively. The mean PDW, MPV, and P-LCR were significantly
      higher in the varicocele group than the control group. CONCLUSION: The results of
      the present study suggest that vascular components may play an important role in
      the pathophysiology of varicocele; therefore, there is a great need for
      prospective studies to confirm this relationship.

PMID- 25045635
TI  - Is elective neck dissection needed in clinically N0 neck in maxillary cancer?

PMID- 25045636
TI  - Evaluation of soft tissue asymmetry using cone-beam computed tomography after
      open reduction and internal fixation of zygomaticomaxillary complex fracture.
AB  - OBJECTIVES: In this study, we assessed soft tissue asymmetry that occurred after
      open reduction of unilateral zygomaticomaxillary complex (ZMC) fractures. We
      proposed a simple method to assess soft tissue asymmetry after reduction surgery
      by evaluating the symmetry between the affected and the unaffected sides. The
      factors affecting soft tissue contour after surgery were also analyzed. MATERIALS
      AND METHODS: Subjects included patients admitted to Wonkwang University Dental
      Hospital from 2008 to 2013. Cone-beam computed tomography (CBCT) images of
      asymmetric patients who underwent open reduction at least 3 months prior were
      compared with healthy patients. RESULTS: The degree of asymmetry was measured in
      both the open reduction and control groups. Landmarks that showed a statistically
      significant difference between the two groups were zygion (1.73+/-0.24 mm),
      bucclae (1.08+/-0.26 mm), point of cheek (2.05+/-0.33 mm) and frontozygomatic
      point (1.30+/-0.31 mm). CONCLUSION: When compared with the normal group,
      asymmetry can occur in the affected side, which usually shows depression of
      overlying soft tissue and is statistically significantly different. Evaluation of
      soft tissue asymmetry with CBCT images after open reduction of ZMC fracture is
      useful.

PMID- 25045637
TI  - Temporomandibular joint dislocation: experiences from Zaria, Nigeria.
AB  - OBJECTIVES: Dislocation of the temporomandibular joint may occur for various
      reasons. Although different invasive methods have been advocated for its
      treatment, this study highlights the value of non-invasive treatment options even
      in chronic cases in a resource-poor environment. MATERIALS AND METHODS: A seven
      year retrospective analysis of all patients managed for temporomandibular joint
      dislocation in our department was undertaken. Patient demographics, risk factors
      associated with temporomandibular joint dislocation and treatment modalities were
      retrieved from patient records. RESULTS: In all, 26 patients were managed over a
      seven-year period. Males accounted for 62% of the patients, and yawning was the
      most frequent etiological factor. Conservative treatment methods were used
      successfully in 86.4% of the patients managed. Two (66.7%) of the three patients
      who needed surgical treatment developed complications, while only one (5.3%)
      patient who was managed conservatively developed complications. CONCLUSION:
      Temporomandibular joint dislocation appears to be associated with male sex,
      middle age, yawning, and low socio-economic status, although these observed
      relationships were not statistically significant. Non-invasive methods remain an
      effective treatment option in this environment in view of the low socio-economic
      status of the patients affected.

PMID- 25045638
TI  - Resorption of bone graft after maxillary sinus grafting and simultaneous implant
      placement.
AB  - OBJECTIVES: The purpose of this study was to evaluate the sinus bone graft
      resorption over 3 years after two-stage implant placement. MATERIALS AND METHODS:
      The subjects for this study included 30 patients whose maxillary posterior ridges
      were too atrophic for implants. Bone-added osteotome sinus floor elevation was
      used in 15 maxillary sinuses, while the bone graft by lateral approach technique
      was used in 25 maxillary sinuses. The height from the top of the fixture to the
      sinus floor was estimated immediately after implant placement and the follow-up
      period was over 3 years. The surgery was classified with two groups: sinus bone
      grafting with and without autogenous bone. All implants were placed
      simultaneously. RESULTS: The mean vertical bone loss was 3.15+/-2.95 mm. The
      survival rate of implants was 94.7%. CONCLUSION: The amount of bone resorption
      was not significantly associated with the surgical methods, the type of bone
      graft materials used, or sinus perforation during surgery.

PMID- 25045639
TI  - A comparative study between data obtained from conventional lateral cephalometry
      and reconstructed three-dimensional computed tomography images.
AB  - OBJECTIVES: The aim of this study was to verify the concordance of the
      measurement values when the same cephalometric analysis method was used for two
      dimensional (2D) cephalometric radiography and three-dimensional computed
      tomography (3D CT), and to identify which 3D Frankfort horizontal (FH) plane was
      the most concordant with FH plane used for cephalometric radiography. MATERIALS
      AND METHODS: Reference horizontal plane was FH plane. Palatal angle and occlusal
      plane angle was evaluated with FH plane. Gonial angle (GA), palatal angle, upper
      occlusal plane angle (UOPA), mandibular plane angle (MPA), U1 to occlusal plane
      angle, U1 to FH plane angle, SNA and SNB were obtained on 2D cephalmetries and
      reconstructed 3D CT. The values measured eight angles in 2D lateral cephalometry
      and reconstructed 3D CT were evaluated by intraclass correlation coefficiency
      (ICC). It also was evaluated to identify 3D FH plane with high degree of
      concordance to 2D one by studying which one in four FH planes shows the highest
      degree of concordance with 2D FH plane. RESULTS: ICCs of MPA (0.752), UOPA
      (0.745), SNA (0.798) and SNB (0.869) were high. On the other hand, ICCs of gonial
      angle (0.583), palatal angle (0.287), U1 to occlusal plane (0.404), U1 to FH
      plane (0.617) were low respectively. Additionally GA and MPA acquired from 2D
      were bigger than those on 3D in all 20 patients included in this study.
      Concordance between one UOPA from 2D and four UOPAs from 3D CT were evaluated by
      ICC values. Results showed no significant difference among four FH planes defined
      on 3D CT. CONCLUSION: FH plane that can be set on 3D CT does not have difference
      in concordance from FH plane on lateral cephalometry. However, it is desirable to
      define FH plane on 3D CT with two orbitales and one porion considering the
      reproduction of orbitale itself.

PMID- 25045640
TI  - Evaluation of subjective satisfaction of dental implant patients.
AB  - OBJECTIVES: The goal of this study was to estimate the overall satisfaction level
      of dental implant patients and further evaluate factors influencing satisfaction.
      MATERIALS AND METHODS: Self-administered questionnaires were mailed to patients
      who received dental implant therapy at Seoul National University Bundang Hospital
      (Seongnam, Korea) from October 2003 to April 2005. The main portion of the
      questionnaire was shared to evaluate the level of satisfaction with implant
      therapy. The questionnaires contained evaluations of influencing factors, which
      were classified as pain-related, service-related, and complication-related.
      RESULTS: The responses from 93 patients (41 males, 52 females) with a total of
      325 implants were included in the analysis, and the mean score for overall
      satisfaction level with implant therapy was 8.26. Female patients showed higher
      visual analogue scale (VAS) scores for both pain during (P=0.000) and after
      implant surgery (P=0.016). Male patients showed more 'negative' values for the
      reasonability of treatment cost (P=0.008) and the adequacy of the treatment
      period (P=0.022). CONCLUSION: The subjective satisfaction of patients was
      influenced by various factors, especially complication-related factors.

PMID- 25045641
TI  - Treatment of extensive comminuted mandibular fracture between both mandibular
      angles with bilateral condylar fractures using a reconstruction plate: a case
      report.
AB  - This following case report describes the open reduction, internal fixation and
      the reconstruction of an extensive comminuted mandibular fracture with bilateral
      condylar fractures in a 19-year-old male patient with an intellectual disability
      and autistic disorder. He suffered fall trauma, resulting in shattered bony
      fragments of the alveolus and mandibular body between both mandibular rami, the
      fracture of both condyles and the avulsion or dislocation of every posterior
      tooth of the mandible. The patient underwent open reduction and internal fixation
      between both mandibular rami using a reconstruction plate, open reduction and
      internal fixation of the shattered fragments using miniplates and screws, and the
      closed reduction of the bilateral condylar fractures. 

PMID- 25045642
TI  - Pigmented villonodular synovitis of the temporomandibular joint - computed
      tomography and magnetic resonance findings: a case report.
AB  - Pigmented villonodular synovitis (PVNS) is a benign but locally aggressive and
      destructive disease originating in the synovial membranes. It is a proliferative
      disorder of unknown etiology. Involvement of the temporomandibular joint (TMJ) is
      very rare. Computed tomography clearly reveals areas of lytic bone erosion and
      sclerosis, and also clearly defines the extent of the tumor which is the focal
      areas of hyperdensity within the soft-tissue mass. Magnetic resonance images
      invariably show profound hypointensity on both T1- and T2-weighted sequences due
      to hemosiderin pigmentation. Additionally, high signal intensity on T2-weighted
      images may indicate cystic loculation of the joint fluid. This case study
      describes a rare case of PVNS of the TMJ with bone destruction of the mandibular
      condyle. Complete surgical excision of the lesion was performed through a
      preauricular approach with temporal extension. During the 10-year follow-up, two
      more operations were performed due to local recurrence and the fracture of the
      reconstruction plate. Total joint reconstruction with Biomet was finally
      performed, and the absence of disease was confirmed with a biopsy report showing
      fibrosis with hyalinization and mild inflammation of the excised soft tissue from
      the old lesion. 

PMID- 25045643
TI  - Brain abscess due to odontogenic infection: a case report.
AB  - In this report, we describe a case of brain abscess due to odontogenic infection.
      A 53-year-old female who had been suffering from headache and trismus for two
      weeks visited the Department of Oral and Maxillofacial Surgery at the Sun Dental
      Hospital (Daejeon, Korea). Even after several routine tests, we still could not
      make a diagnosis. However, after the combined multidisciplinary efforts of oral
      surgeons and neurosurgeons, the patient was treated for odontogenic infection and
      made an uneventful recovery. Therefore, patients with infections in the head and
      neck region showing symptoms such as headache, changes in mental state, nausea,
      vomiting, seizures, hemiplegia, speech disturbance, and visual disturbance, a
      brain abscess should be included in the list of differential diagnoses. 

PMID- 25045645
TI  - Arachnoid Membrane Suturing for Prevention of Subdural Fluid Collection in
      Extracranial-intracranial Bypass Surgery.
AB  - OBJECTIVE: Water-tight closure of the dura in extracranial-intracranial (EC-IC)
      bypass is impossible because the superficial temporal artery (STA) must run
      through the dural defect. Consequently, subdural hygroma and subcutaneous
      cerebrospinal fluid (CSF) collection frequently occur postoperatively. To reduce
      these complications, we prospectively performed suturing of the arachnoid
      membrane after STA-middle cerebral artery (STA-MCA) and evaluated the clinical
      usefulness. MATERIALS AND METHODS: Between Mar. 2005 and Oct. 2010, extracranial
      intracranial arterial bypass (EIAB) with/without encephalo-myo-synangiosis was
      performed in 88 cases (male : female = 53 : 35). As a control group, 51 patients
      (57 sides) underwent conventional bypass surgery without closure of the arachnoid
      membrane. Postoperative computed tomography (CT) scan was performed twice in
      three days and seven days later, respectively, for evaluation of the presence of
      subdural fluid collection and other mass lesions. RESULTS: The surgical result
      was excellent, with no newly developing ischemic event until recent follow-up.
      The additional time needed for arachnoid suture was five to ten minutes, when
      three to eight sutures were required. Post-operative subdural fluid collection
      was not seen on follow-up computed tomography scans in all patients. CONCLUSION:
      Arachnoid suturing is simple, safe, and effective for prevention of subdural
      fluid collection in EC-IC bypass surgery, especially the vulnerable ischemic
      hemisphere.

PMID- 25045646
TI  - Comparison of Incidence and Risk Factors for Shunt-dependent Hydrocephalus in
      Aneurysmal Subarachnoid Hemorrhage Patients.
AB  - OBJECTIVE: The objective of this study was to compare the incidence of
      ventricular shunt placement for shunt-dependent hydrocephalus (SDHC) after
      clipping versus coiling of ruptured aneurysms. MATERIALS AND METHODS: A
      retrospective review was conducted in 215 patients with aneurysmal subarachnoid
      hemorrhage (SAH) who underwent surgical clipping or endovascular coiling during
      the period from May 2008 to December 2011. Relevant clinical and radiographic
      data were analyzed with regard to the incidence of hydrocephalus and ventriculo
      peritoneal shunt (VPS). Patients treated with clipping were assigned to Group A,
      while those treated with coiling were assigned to Group B. RESULTS: Of 215
      patients (157 clipping, 58 coiling), no significant difference in the incidence
      of final VPS was observed between treatment modalities (15.3% vs. 10.3%) (p =
      0.35). Independent risk factors for VPS for treatment of chronic hydrocephalus
      were as follows: (1) older than 65 years, (2) poorer Hunt-Hess grade IV and V,
      (3) Fisher grade III and IV, and (4) particularly initial presence of an
      intraventricular hemorrhage. CONCLUSION: In this study comparing two modalities
      for treatment of aneurysm, there was no difference in the incidence of chronic
      hydrocephalus requiring VPS. A significantly higher rate of shunt dependency was
      observed for age older than 65 years, poor initial neurological status, and thick
      SAH with presence of initial intraventricular hemorrhage. By understanding these
      factors related to development of SDHC and results, it is expected that
      management of aneurysmal SAH will result in a better prognosis.

PMID- 25045647
TI  - Diagnostic Value of Thrombus Size on T2(*)-weighted Gradient Echo Imaging in
      Acute Middle Cerebral Artery Occlusion.
AB  - OBJECTIVE: The T2(*)-weighted gradient echo image susceptibility vessel sign (GRE
      SVS) is a well-known indicator of intraluminal thrombi in acute cerebral
      infarction. The purpose of this study was to evaluate the relationships between
      thrombus size on GRE SVS and recanalization after intravenous administration of
      tissue plasminogen activator (IV-tPA). MATERIALS AND METHODS: Fifty five patients
      with GRE SVSs on the M1 were enrolled. Examination of magnetic resonance image
      (MRI), including diffusion weighted imaging and MR angiography, was performed
      within 20 minutes of admission. Thrombus size on GRE was calculated using the
      Picture Archiving and Communication System upon initial MRI. Recanalization was
      assessed with follow-up MRI or transfemoral cerebral angiography within 24 hours
      of treatment. RESULTS: The patient group consisted of 37 males and 18 females
      with an average age of 63.74 +/- 10.28 years (range: 43 - 77 years). The median
      NIHSS score was 13. Fifteen of these patients achieved recanalization (27.3%).
      The average thrombus cross-sectional area in the recanalization group was 38.54
      +/- 20.27 mm(2), and the corresponding size of the non-recanalization group was
      53.38 +/- 24.77 mm(2) (p = 0.043). In the receiver operator characteristic curve
      for thrombus cross-sectional area in relation to recanalization, the cut-off
      point was 47.28 mm(2). The sensitivity at this cut-off point was 73.3%, the
      specificity was 60%, and the area under the curve was 0.687. CONCLUSION: Thrombus
      size on GRE is a simple diagnostic tool that can be easily measured, and thrombus
      size on GRE SVS was found to be associated with recanalization after IV-tPA.

PMID- 25045648
TI  - Symptomatic Cerebral Air Embolism During Stent-assisted Coiling of an Unruptured
      Middle Cerebral Artery Aneurysm: Intraoperative Diagnosis and Management of a
      Rare Complication.
AB  - Symptomatic cerebral air embolism during cerebral angiography is extremely rare.
      We report on the case of a 69-year-old woman undergoing elective stent-assisted
      coiling of an unruptured right middle cerebral artery (MCA) bifurcation aneurysm,
      who was found to have severe attenuation of somatosensory evoked potential (SSEP)
      and electroencephalography (EEG) during the procedure. Intra-operative DynaCT
      showed hypodense cortical vessels consistent with cerebral air embolism.
      Diagnostic and management strategies for this rare complication are reviewed. 

PMID- 25045649
TI  - Pial arteriovenous fistula with giant varices: report of two cases with good
      surgical outcome.
AB  - Pial arteriovenous fistulas (pAVF) are rare vascular lesions consisting of one or
      more arterial connections to a single venous channel without any intervening
      nidus of vessels or capillaries. Case 1: A 65-year-old woman with a complaint of
      headache and left hand paresthesia was referred to us. Magnetic resonance imaging
      showed a large saccular lesion with signal void in the posterior part of the
      right sylvian fissure and catheter angiography showed a giant venous aneurysm fed
      by one branch of the middle cerebral artery (MCA) and draining into the vein of
      Trolard. Case 2: A 12-year-old boy was transferred to our hospital with a history
      of sudden loss of consciousness and hemiplegia. Brain computed tomography
      revealed a massive hemorrhagic mass in the right hemisphere and cerebral
      angiography showed a pAVF with a large aneurysmal varix, which was fed by
      multiple branches of the right MCA and draining into the superior sagittal sinus.
      Both patients underwent craniotomy and after ligation of vascular connections,
      aneurysmal varices were removed completely. Surgical resection can be a safe
      method for treatment of pAVFs, particularly in those with large varices. 

PMID- 25045650
TI  - Multiple spontaneous simultaneous intracerebral hemorrhages.
AB  - Simultaneous occurrence of intracerebral hemorrhage (ICH) in different arterial
      territories is an uncommon event. We report on two cases of multiple spontaneous
      simultaneous ICH for which we could find no specific cause. A 73-year-old man,
      with no related medical history, was admitted to the hospital with simultaneous
      bithalamic ICH, and subsequently died of recurrent pneumonia. Second patient was
      a 60-year-old man who presented with simultaneous ICH in the pons and thalamus;
      he died of recurrent bleeding. We review the possible pathological mechanisms,
      clinical and radiologic features of simultaneous multiple ICH. 

PMID- 25045651
TI  - Pipeline embolization device for giant internal carotid artery aneurysms: 9-month
      follow-up results of two cases.
AB  - The pipelineTM embolization device (PED) is a braided, tubular, bimetallic
      endoluminal implant used for occlusion of intracranial aneurysms through flow
      disruption along the aneurysm neck. The authors report on two cases of giant
      internal carotid artery aneurysm treated with the PED. In the first case, an
      aneurysm measuring 26.4 mm was observed at the C3-C4 portion of the left internal
      carotid artery in a 64-year-old woman who underwent magnetic resonance imaging
      (MRI) for dizziness and diplopia. In the second case, MRI showed an aneurysm
      measuring 25 mm at the C4-C5 portion of the right internal carotid artery in a 39
      year-old woman with right ptosis and diplopia. Each giant aneurysm was treated
      with deployment of a PED (3.75 mm diameter/20 mm length and 4.5 mm diameter/25 mm
      length, respectively). Nine months later, both cases showed complete radiological
      occlusion of the giant intracranial aneurysm and sac shrinkage. We suggest that
      use of the PED can be a therapeutic option for giant intracranial aneurysms. 

PMID- 25045652
TI  - Two cases of subarachnoid hemorrhage from spontaneous anterior cerebral artery
      dissection : a case of simultaneous hemorrhage and ischemia without aneurysmal
      formation and another case of hemorrhage with aneurysmal formation.
AB  - Spontaneous anterior cerebral artery (ACA) dissection, although extremely rare,
      is often associated with severe morbidity and mortality. It could lead to
      cerebral hemorrhage, ischemic stroke, or, rarely, combination of hemorrhage and
      ischemia due to hemodynamic changes. Prompt and accurate diagnosis is essential
      for determining the appropriate management. However, the optimal treatment for
      ACA dissection remains controversial. Herein, we report on two rare cases of
      subarachnoid hemorrhage (SAH) caused by ACA dissection; a case presenting with
      simultaneous SAH and infarction without aneurysmal formation and another case
      presenting with SAH with fusiform aneurysmal formation. A review of the related
      literature is provided, and optimal treatments for each type of dissection are
      suggested. 

PMID- 25045653
TI  - Balloon anchor technique for pipeline embolization device deployment across the
      neck of a giant intracranial aneurysm.
AB  - Treatment of giant intracranial aneurysms, via either surgical or endovascular
      approaches, is associated with a high level of technical difficulty as well as a
      high rate of treatment-related morbidity and mortality. Flow-diverting stents,
      such as the Pipeline embolization device (PED), have drastically altered the
      therapeutic strategies for the treatment of giant aneurysms. Gaining endovascular
      access using a microcatheter to the portion of the parent artery distal to the
      aneurysm neck is requisite for safe and effective stent deployment. Giant
      aneurysms are often associated with vascular tortuosity, which necessitates
      significant catheter support systems to enable maneuvering of PEDs across the
      aneurysm neck. This is also required in order to reduce the probability of stent
      herniation within giant aneurysms. We report on a case of a giant supraclinoid
      internal carotid artery (ICA) aneurysm which was treated successfully with a PED
      utilizing a balloon anchor technique to facilitate direct microcatheter access
      across the aneurysm neck. 

PMID- 25045654
TI  - Ten years of tuberculosis intervention in Greenland - has it prevented cases of
      childhood tuberculosis?
AB  - BACKGROUND: The incidence of tuberculosis (TB) disease in Greenland doubled in
      the 1990s. To combat the increase, national TB interventions were initiated in
      2000 and strengthened in 2007. OBJECTIVE: To determine whether the effect of
      interventions could be detected, we estimated the TB disease risk among
      children<=15 years before and after interventions were implemented. DESIGN: For a
      study cohort, we recruited all children <=15 years of age included in the
      Greenlandic Civil Registration System (CRS) from 1990 to 2010. The CRS identifier
      was used to link cohort participants with TB cases identified based on the
      Greenlandic National TB registry. Bacille Calmette Guerin (BCG) vaccination
      status was identified through year of birth, as BCG was offered to newborns born
      either before 1991 or after 1996. Years with interventions were defined as 2000
      2006 (primary interventions) and 2007-2010 (intensified interventions). Risk of
      TB was estimated using Poisson regression. RESULTS: The study included 35,858
      children, of whom 209 had TB disease. The TB disease incidence decreased after
      interventions were implemented (2007-2010: IRR [incidence rate ratios] 0.62, 95%
      CI: 0.39-0.95, p=0.03, compared with the 1995-1999 period). The TB disease risk
      was inversely associated with BCG vaccination (IRR: 0.54, 95% CI: 0.41-0.72,
      p<0.001). CONCLUSIONS: Years with national TB interventions in Greenland,
      including neonate BCG vaccination, are associated with a lower TB disease
      incidence among children <=15 years of age.

PMID- 25045655
TI  - Protective effects of testosterone on presynaptic terminals against oligomeric
      beta-amyloid peptide in primary culture of hippocampal neurons.
AB  - Increasing lines of evidence support that testosterone may have neuroprotective
      effects. While observational studies reported an association between higher
      bioavailable testosterone or brain testosterone levels and reduced risk of
      Alzheimer's disease (AD), there is limited understanding of the underlying
      neuroprotective mechanisms. Previous studies demonstrated that testosterone could
      alleviate neurotoxicity induced by beta-amyloid (Abeta), but these findings
      mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration
      are early events during the pathogenesis of AD, we aim to investigate the effects
      of testosterone on oligomeric Abeta-induced synaptic changes. Our data suggested
      that exposure of primary cultured hippocampal neurons to oligomeric Abeta could
      reduce the length of neurites and decrease the expression of presynaptic proteins
      including synaptophysin, synaptotagmin, and synapsin-1. Abeta also disrupted
      synaptic vesicle recycling and protein folding machinery. Testosterone preserved
      the integrity of neurites and the expression of presynaptic proteins. It also
      attenuated Abeta-induced impairment of synaptic exocytosis. By using letrozole as
      an aromatase antagonist, we further demonstrated that the effects of testosterone
      on exocytosis were unlikely to be mediated through the estrogen receptor pathway.
      Furthermore, we showed that testosterone could attenuate Abeta-induced reduction
      of HSP70, which suggests a novel mechanism that links testosterone and its
      protective function on Abeta-induced synaptic damage. Taken together, our data
      provide further evidence on the beneficial effects of testosterone, which may be
      useful for future drug development for AD. 

PMID- 25045656
TI  - NTPDase5/PCPH as a new target in highly aggressive tumors: a systematic review.
AB  - The protooncogene PCPH was recently identified as being the ectonucleoside
      triphosphate diphosphohydrolase 5 (ENTPD5). This protooncogene is converted into
      an oncogene by a single base pair deletion, resulting in frame change and
      producing a premature stop codon, leading to a mutated protein (mt-PCPH) with
      only 27 kDa, which is much smaller than the original 47 kDa protein.
      Overexpression of the PCPH as well as the mutated PCPH increases the cellular
      resistance to stress and apoptosis. This is intriguing considering that the
      active form, that is, the oncogene, is the mutated PCPH. Several studies analyzed
      the expression of NTPDase5/mt-PCPH in a wide range of tumor cells and evaluated
      its role and mechanisms in cancer and other pathogenic processes. The main point
      of this review is to integrate the findings and proposed theories about the role
      played by NTPDase5/mt-PCPH in cancer progression, considering that these proteins
      have been suggested as potential early diagnostic tools and therapy targets. 

PMID- 25045657
TI  - In silico investigation of potential mTOR inhibitors from traditional Chinese
      medicine for treatment of Leigh syndrome.
AB  - A recent research demonstrates that the inhibition of mammalian target of
      rapamycin (mTOR) improves survival and health for patients with Leigh syndrome.
      mTOR proteins can be treated as drug target proteins against Leigh syndrome and
      other mitochondrial disorders. In this study, we aim to identify potent TCM
      compounds from the TCM Database@Taiwan as lead compounds of mTOR inhibitors.
      PONDR-Fit protocol was employed to predict the disordered disposition in mTOR
      protein before virtual screening. After virtual screening, the MD simulation was
      employed to validate the stability of interactions between each ligand and mTOR
      protein in the docking poses from docking simulation. The top TCM compounds,
      picrasidine M and acerosin, have higher binding affinities with target protein in
      docking simulation than control. There have H-bonds with residues Val2240 and pi
      interactions with common residue Trp2239. After MD simulation, the top TCM
      compounds maintain similar docking poses under dynamic conditions. The top two
      TCM compounds, picrasidine M and acerosin, were extracted from Picrasma
      quassioides (D. Don) Benn. and Vitex negundo L. Hence, we propose the TCM
      compounds, picrasidine M and acerosin, as potential candidates as lead compounds
      for further study in drug development process with the mTOR protein against Leigh
      syndrome and other mitochondrial disorders. 

PMID- 25045658
TI  - Extended genetic diversity of bovine viral diarrhea virus and frequency of
      genotypes and subtypes in cattle in Italy between 1995 and 2013.
AB  - Genetic typing of bovine viral diarrhea virus (BVDV) has distinguished BVDV-1 and
      BVDV-2 species and an emerging putative third species (HoBi-like virus), recently
      detected in southern Italy, signaling the occurrence of natural infection in
      Europe. Recognizing the need to update the data on BVDV genetic variability in
      Italy for mounting local and European alerts, a wide collection of 5' UTR
      sequences (n = 371) was selected to identify the frequency of genotypes and
      subtypes at the herd level. BVDV-1 had the highest frequency, followed by
      sporadic BVDV-2. No novel HoBi-like viruses were identified. Four distribution
      patterns of BVDV-1 subtypes were observed: highly prevalent subtypes with a wide
      temporal-spatial distribution (1b and 1e), low prevalent subtypes with a
      widespread geographic distribution (1a, 1d, 1g, 1h, and 1k) or a restricted
      geographic distribution (1f), and sporadic subtypes detected only in single herds
      (1c, 1j, and 1l). BVDV-1c, k, and l are reported for the first time in Italy. A
      unique genetic variant was detected in the majority of herds, but cocirculation
      of genetic variants was also observed. Northern Italy ranked first for BVDV
      introduction, prevalence, and dispersion. Nevertheless, the presence of sporadic
      variants in other restricted areas suggests the risk of different routes of BVDV
      introduction. 

PMID- 25045659
TI  - Multipotent neural crest stem cell-like cells from rat vibrissa dermal papilla
      induce neuronal differentiation of PC12 cells.
AB  - Bone marrow mesenchymal stem cells (BMSCs) transplants have been approved for
      treating central nervous system (CNS) injuries and diseases; however, their
      clinical applications are limited. Here, we model the therapeutic potential of
      dermal papilla cells (DPCs) in vitro. DPCs were isolated from rat vibrissae and
      characterized by immunocytofluorescence, RT-PCR, and multidifferentiation assays.
      We examined whether these cells could secrete neurotrophic factors (NTFs) by
      using cocultures of rat pheochromocytoma cells (PC12) with conditioned medium and
      ELISA assay. DPCs expressed Sox10, P75, Nestin, Sox9, and differentiated into
      adipocytes, osteoblasts, smooth muscle cells, and neurons under specific inducing
      conditions. The DPC-conditioned medium (DPC-CM) induced neuronal differentiation
      of PC12 cells and promoted neurite outgrowth. Results of ELISA assay showed that
      compared to BMSCs, DPCs secreted more brain-derived neurotrophic factor (BDNF)
      and glial cell line-derived neurotrophic factor (GDNF). Moreover, we observed
      that, compared with the total DPC population, sphere-forming DPCs expressed
      higher levels of Nestin and P75 and secreted greater amounts of GDNF. The DPCs
      from craniofacial hair follicle papilla may be a new and promising source for
      treating CNS injuries and diseases. 

PMID- 25045660
TI  - The establishment of metabolic syndrome model by induction of fructose drinking
      water in male Wistar rats.
AB  - BACKGROUND: Metabolic syndrome can be caused by modification of diet by means of
      consumption of high carbohydrate and high fat diet such as fructose. AIMS: To
      develop a metabolic syndrome rat model by induction of fructose drinking water
      (FDW) in male Wistar rats. METHODS: Eighteen male Wistar rats were fed with FDW
      20% and FDW 25% for a duration of eight weeks. The physiological changes with
      regard to food and fluid intake, as well as calorie intake, were measured. The
      metabolic changes such as obesity, dyslipidaemia, hypertension, and
      hyperglycaemia were determined. Data was presented in mean +/- SEM subjected to
      one-way ANOVA. RESULTS: Male Wistar rats fed with FDW 20% for eight weeks
      developed significant higher obesity parameters compared to those fed with FDW
      25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic
      hypertension, hypertriglyceridemia, and hyperglycemia in both groups. CONCLUSION:
      We conclude that the metabolic syndrome rat model is best established with the
      induction of FDW 20% for eight weeks. This was evident in the form of higher
      obesity parameter which caused the development of the metabolic syndrome.

PMID- 25045662
TI  - Metadynamics simulation study on the conformational transformation of HhaI
      methyltransferase: an induced-fit base-flipping hypothesis.
AB  - DNA methyltransferases play crucial roles in establishing and maintenance of DNA
      methylation, which is an important epigenetic mark. Flipping the target cytosine
      out of the DNA helical stack and into the active site of protein provides DNA
      methyltransferases with an opportunity to access and modify the genetic
      information hidden in DNA. To investigate the conversion process of base flipping
      in the HhaI methyltransferase (M.HhaI), we performed different molecular
      simulation approaches on M.HhaI-DNA-S-adenosylhomocysteine ternary complex. The
      results demonstrate that the nonspecific binding of DNA to M.HhaI is initially
      induced by electrostatic interactions. Differences in chemical environment
      between the major and minor grooves determine the orientation of DNA. Gln237 at
      the target recognition loop recognizes the GCGC base pair from the major groove
      side by hydrogen bonds. In addition, catalytic loop motion is a key factor during
      this process. Our study indicates that base flipping is likely to be an "induced
      fit" process. This study provides a solid foundation for future studies on the
      discovery and development of mechanism-based DNA methyltransferases regulators. 

PMID- 25045663
TI  - Admission cell free DNA as a prognostic factor in burns: quantification by use of
      a direct rapid fluorometric technique.
AB  - BACKGROUND: Despite great advances in the treatment of burn patients, useful
      prognostic markers are sparse. During the past years there has been increasing
      interest in circulating plasma cell free DNA as a potential marker for tissue
      injury. We have developed a rapid direct fluorescent assay for cell free DNA
      quantification that allows obtaining accurate, fast, and inexpensive
      measurements. OBJECTIVE: To use this technique for measuring plasma cell free DNA
      levels in burn patients and to further explore the use of cell free DNA as a
      potential marker of patient outcome in burns. METHODS: Cell free DNA levels
      obtained from 14 burn victims within 6 hours of injury and 14 healthy controls
      were quantified by a direct rapid fluorometric assay. RESULTS: Patient admission
      cell free DNA levels were significantly elevated compared with that of controls
      (1797 +/- 1523 ng/mL versus 374 +/- 245 ng/mL, P = 0.004). There are
      statistically significant correlations between cell free DNA admission levels and
      burn degree (Spearman's correlation = 0.78, P = 0.001), total body surface area
      (Spearman's correlation = 0.61, P = 0.02), and total burn volume (Spearman's
      correlation = 0.64, P = 0.014). CONCLUSIONS: Admission cell free DNA levels can
      serve as a prognostic factor in burns and future routine use can be made possible
      by use of our direct rapid fluorometric assay.

PMID- 25045661
TI  - Integration analysis of microRNA and mRNA expression profiles in human peripheral
      blood lymphocytes cultured in modeled microgravity.
AB  - We analyzed miRNA and mRNA expression profiles in human peripheral blood
      lymphocytes (PBLs) incubated in microgravity condition, simulated by a ground
      based rotating wall vessel (RWV) bioreactor. Our results show that 42 miRNAs were
      differentially expressed in MMG-incubated PBLs compared with 1 g incubated ones.
      Among these, miR-9-5p, miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p were the
      most dysregulated. To improve the detection of functional miRNA-mRNA pairs, we
      performed gene expression profiles on the same samples assayed for miRNA
      profiling and we integrated miRNA and mRNA expression data. The functional
      classification of miRNA-correlated genes evidenced significant enrichment in the
      biological processes of immune/inflammatory response, signal transduction,
      regulation of response to stress, regulation of programmed cell death, and
      regulation of cell proliferation. We identified the correlation of miR-9-3p, miR
      155-5p, miR-150-3p, and miR-378-3p expression with that of genes involved in
      immune/inflammatory response (e.g., IFNG and IL17F), apoptosis (e.g., PDCD4 and
      PTEN), and cell proliferation (e.g., NKX3-1 and GADD45A). Experimental assays of
      cell viability and apoptosis induction validated the results obtained by
      bioinformatics analyses demonstrating that in human PBLs the exposure to reduced
      gravitational force increases the frequency of apoptosis and decreases cell
      proliferation. 

PMID- 25045664
TI  - An integrated analysis of miRNA, lncRNA, and mRNA expression profiles.
AB  - Increasing amounts of evidence indicate that noncoding RNAs (ncRNAs) have
      important roles in various biological processes. Here, miRNA, lncRNA, and mRNA
      expression profiles were analyzed in human HepG2 and L02 cells using high
      throughput technologies. An integrative method was developed to identify possible
      functional relationships between different RNA molecules. The dominant
      deregulated miRNAs were prone to be downregulated in tumor cells, and the most
      abnormal mRNAs and lncRNAs were always upregulated. However, the genome-wide
      analysis of differentially expressed RNA species did not show significant bias
      between up- and downregulated populations. miRNA-mRNA interaction was performed
      based on their regulatory relationships, and miRNA-lncRNA and mRNA-lncRNA
      interactions were thoroughly surveyed and identified based on their locational
      distributions and sequence correlations. Aberrantly expressed miRNAs were further
      analyzed based on their multiple isomiRs. IsomiR repertoires and expression
      patterns were varied across miRNA loci. Several specific miRNA loci showed
      differences between tumor and normal cells, especially with respect to abnormally
      expressed miRNA species. These findings suggest that isomiR repertoires and
      expression patterns might contribute to tumorigenesis through different
      biological roles. Systematic and integrative analysis of different RNA molecules
      with potential cross-talk may make great contributions to the unveiling of the
      complex mechanisms underlying tumorigenesis. 

PMID- 25045665
TI  - Hematological and biochemical markers of iron status in a male, young, physically
      active population.
AB  - The aim of this study was to establish reference intervals (RIs) for the hemogram
      and iron status biomarkers in a physically active population. The study
      population included male volunteers (n = 150) with an average age of 19 +/- 1
      years who had participated in a regular and controlled exercise program for four
      months. Blood samples were collected to determine hematological parameters using
      a Sysmex XE-5000 analyzer (Sysmex, Kobe, Japan). Iron, total iron-binding
      capacity (TIBC), transferrin saturation and ferritin, and high-sensitivity C
      reactive protein (CRP) concentrations in serum samples were measured using
      commercial kits (Roche Diagnostics, GmbH, Mannheim, Germany) and a Roche/Hitachi
      902 analyzer. The RIs were established using the RefVal program 4.1b. The
      leucocyte count, TIBC, and CRP and ferritin concentrations exhibited higher RIs
      compared with those in a nonphysically active population. Thirty volunteers
      (outliers) were removed from the reference population due to blood abnormalities.
      Among the outliers, 46% exhibited higher CRP concentrations and lower
      concentrations of iron and reticulocyte hemoglobin compared with the
      nonphysically active population (P < 0.001). Our results showed that it is
      important to establish RIs for certain laboratory parameters in a physically
      active population, especially for tests related to the inflammatory response and
      iron metabolism. 

PMID- 25045666
TI  - The impact of coinfections and their simultaneous transmission on antigenic
      diversity and epidemic cycling of infectious diseases.
AB  - Epidemic cycling in human infectious diseases is common; however, its underlying
      mechanisms have been poorly understood. Much effort has been made to search for
      external mechanisms. Multiple strains of an infectious agent were usually
      observed and coinfections were frequent; further, empirical evidence indicates
      the simultaneous transmission of coinfections. To explore intrinsic mechanisms
      for epidemic cycling, in this study we consider a multistrain Susceptible
      Infected-Recovered-Susceptible epidemic model by including coinfections and
      simultaneous transmission. We show that coinfections and their simultaneous
      transmission widen the parameter range for coexistence and coinfections become
      popular when strains enhance each other and the immunity wanes quickly. However,
      the total prevalence is nearly independent of these characteristics and
      approximated by that of one-strain model. With sufficient simultaneous
      transmission and antigenic diversity, cyclical epidemics can be generated even
      when strains interfere with each other by reducing infectivity. This indicates
      that strain interactions within coinfections and cross-immunity during subsequent
      infection provide a possible intrinsic mechanism for epidemic cycling. 

PMID- 25045667
TI  - KCTD11 tumor suppressor gene expression is reduced in prostate adenocarcinoma.
AB  - Prostate cancer is the most common noncutaneous cancer among men in the United
      States. A genetic contribution to prostate cancer risk has been documented, but
      knowledge of the molecular mechanisms involved in prostate cancer initiation is
      still not well understood. Loss of heterozygosity (LOH) of chromosomal regions is
      crucial in tumor progression. In human prostate cancer, several chromosomal
      regions demonstrating a high frequency of LOH have been previously identified.
      KCTD11 (REN) is a tumor suppressor gene mapping on human chromosome 17p13.2,
      whose expression is frequently lost in human medulloblastoma and in several other
      cancer types. KCTD11 acts as a negative regulator of the Hedgehog (Hh) signaling.
      Here, we demonstrated that KCTD11 LOH is a common genetic lesion in human
      prostate adenocarcinoma. Indeed, nuclear KCTD11 protein expression is strongly
      reduced in primary prostate cancer, and this event correlated with overexpression
      of proteins acting into the Hedgehog pathway. Low levels of KCTD11 mRNA have been
      also observed in prostatic cancer cells, and ectopic overexpression of KCTD11 led
      to growth arrest. Our study demonstrates and supports that KCTD11, as well as
      negatively regulated downstream effectors belonging to Hh signaling, plays a role
      in prostate cancer pathogenesis. This could be suitable to characterize new
      diagnostic and therapeutic markers. 

PMID- 25045668
TI  - Angiotensin converting enzyme inhibition reduces cardiovascular responses to
      acute stress in myocardially infarcted and chronically stressed rats.
AB  - Previous studies showed that chronically stressed and myocardially infarcted rats
      respond with exaggerated cardiovascular responses to acute stress. The present
      experiments were designed to elucidate whether this effect can be abolished by
      treatment with the angiotensin converting enzyme (ACE) inhibitor captopril.
      Sprague Dawley rats were subjected either to sham surgery (Groups 1 and 2) or to
      myocardial infarction (Groups 3 and 4). The rats of Groups 2 and 4 were also
      exposed to mild chronic stressing. Four weeks after the operation, mean arterial
      blood pressure (MABP) and heart rate (HR) were measured under resting conditions
      and after application of acute stress. The cardiovascular responses to the acute
      stress were determined again 24 h after administration of captopril orally.
      Captopril significantly reduced resting MABP in each group. Before administration
      of captopril, the maximum increases in MABP evoked by the acute stressor in all
      (infarcted and sham-operated) chronically stressed rats and also in the infarcted
      nonchronically stressed rats were significantly greater than in the sham-operated
      rats not exposed to chronic stressing. These differences were abolished by
      captopril. The results suggest that ACE may improve tolerance of acute stress in
      heart failure and during chronic stressing. 

PMID- 25045669
TI  - Adiponectin levels are reduced while markers of systemic inflammation and aortic
      remodelling are increased in intrauterine growth restricted mother-child couple.
AB  - AIM OF THE STUDY: To investigate the relationships between the adipocytokine
      levels, markers of inflammation, and vascular remodelling in pregnancies
      complicated by intrauterine growth restriction (IUGR). MATERIALS AND METHODS:
      This was a retrospective study. One hundred and forty pregnant patients were
      enrolled. Adiponectin, leptin, tumor necrosis factor alpha (TNFalpha),
      interleukin-6 (IL-6), and C reactive protein (CRP) were assessed in IUGR, small
      for gestational age (SGA), and appropriate for gestational age (AGA) mother-child
      couples at delivery. IUGR and SGA fetuses were defined as fetuses whose estimated
      fetal weight (EFW) was below 10th percentile for gestational age with and without
      umbilical artery (UA) Doppler abnormalities, respectively. Fetal aorta intima
      media thickness (aIMT) was evaluated by ultrasound in the same fetal groups. Data
      were analyzed by R (version 2.15.2). RESULTS: There were 37 IUGR mother-child
      couples, 33 SGA, and 70 AGA. Leptin, TNFalpha, IL-6, and CRP serum levels were
      higher in IUGR pregnant patients (P < 0.05). Adiponectin levels were
      significantly reduced in IUGR fetuses compared to SGA and AGA, while leptin,
      TNFalpha, and IL-6 levels were higher in IUGR group (P <= 0.05). Fetal aIMT was
      significantly higher in IUGR (P < 0.05) and in this group there was a negative
      correlation between aIMT and adiponectin/leptin ratio (A/L ratio) (P < 0.05) and
      between adiponectin and IL-6 levels (P < 0.05). CONCLUSIONS: In conclusion,
      compared to SGA and AGA, IUGR fetuses had reduced circulating levels of
      adiponectin and elevated measures of aIMT and several inflammatory markers.
      Moreover, adiponectin levels were negatively correlated with aIMT in IUGR fetuses
      suggesting a possible causal link between reduced adiponectin and vessel
      remodelling.

PMID- 25045670
TI  - Long non-coding RNA deregulation in tongue squamous cell carcinoma.
AB  - BACKGROUND: The deregulated tumorigenic long non-coding RNA (lncRNA) has been
      reported in several malignancies. However, there is still no comprehensive study
      on tongue squamous cell carcinoma (SCC). METHODS: Functional reannotation for the
      human lncRNA was carried out by ncFANs. Real-time quantitative PCR was used to
      validate the identified lncRNAs. RESULTS: Using the functional annotation
      algorithm from ncFANs, 8 differentially expressed lncRNAs were identified. Lnc
      PPP2R4-5, lnc-SPRR2D-1, lnc-MAN1A2-1, lnc-FAM46A-1, lnc-MBL2-4:1, and lnc-MBL2
      4:3 were upregulated in the microdissected tongue SCC tissues. In comparison, lnc
      AL355149.1-1 and lnc-STXBP5-1 showed significant downregulation. High level of
      lnc-MBL2-4:3 was significantly associated with the node positive tongue SCC
      patients. Further, patients with advanced T-stage demonstrated a further
      reduction of lnc-AL355149.1-1 in the tumor tissues. Treatment of tongue SCC cells
      with 5-fluorouracil and paclitaxel can reserve the expression patterns observed
      in the tongue SCC tissues. Further, changes of lnc-MBL2-4:3 and lnc-AL355149.1-1
      expression levels were noticed in the cisplatin-resistant tongue SCC cells.
      CONCLUSIONS: Our results demonstrated that functional reannotation allows us to
      identify novel lncRNAs using the existing gene expression array dataset. The
      association of lncRNA with the T-stage and nodal status of tongue SCC patients
      suggested that lncRNA deregulation was involved in the pathogenesis of tongue
      SCC.

PMID- 25045671
TI  - Topical delivery of aceclofenac: challenges and promises of novel drug delivery
      systems.
AB  - Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect
      about 60 million people of total world population by 2020. The associated pain
      and disability impair the quality of life and also pose economic burden to the
      patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in
      OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient
      friendly, as they cause various gastrointestinal adverse effects like bleeding,
      ulceration, and perforation. To enhance the tolerability of diclofenac and
      decrease the common side effects, aceclofenac (ACE) was developed by its chemical
      modification. As expected, ACE is more well-tolerated than diclofenac and
      possesses superior efficacy but is not completely devoid of the NSAID-tagged side
      effects. A series of chemical modifications of already planned drug is
      unjustified as it consumes quanta of time, efforts, and money, and this approach
      will also pose stringent regulatory challenges. Therefore, it is justified to
      deliver ACE employing tools of drug delivery and nanotechnology to refine its
      safety profile. The present review highlights the constraints related to the
      topical delivery of ACE and the various attempts made so far for the safe and
      effective topical delivery employing the novel materials and methods. 

PMID- 25045672
TI  - Purification and characterization of catalase from marine bacterium Acinetobacter
      sp. YS0810.
AB  - The catalase from marine bacterium Acinetobacter sp. YS0810 (YS0810CAT) was
      purified and characterized. Consecutive steps were used to achieve the purified
      enzyme as follows: ethanol precipitation, DEAE Sepharose ion exchange, Superdex
      200 gel filtration, and Resource Q ion exchange. The active enzyme consisted of
      four identical subunits of 57.256 kDa. It showed a Soret peak at 405 nm,
      indicating the presence of iron protoporphyrin IX. The catalase was not
      apparently reduced by sodium dithionite but was inhibited by 3-amino-1,2,4
      triazole, hydroxylamine hydrochloride, and sodium azide. Peroxidase-like activity
      was not found with the substrate o-phenylenediamine. So the catalase was
      determined to be a monofunctional catalase. N-terminal amino acid of the catalase
      analysis gave the sequence SQDPKKCPVTHLTTE, which showed high degree of homology
      with those of known catalases from bacteria. The analysis of amino acid sequence
      of the purified catalase by matrix-assisted laser desorption ionization time-of
      flight mass spectrometry showed that it was a new catalase, in spite of its high
      homology with those of known catalases from other bacteria. The catalase showed
      high alkali stability and thermostability.

PMID- 25045673
TI  - Acoustic radiation force impulse imaging: a new tool for the diagnosis of
      papillary thyroid microcarcinoma.
AB  - PURPOSE: To evaluate the diagnostic performance of ARFI imaging in
      differentiating between benign and malignant thyroid nodules <1 cm. MATERIALS AND
      METHODS: 173 pathologically proven thyroid nodules (77 benign, 96 malignant) in
      157 patients were included in this study. Receiver-operating characteristic curve
      (ROC) analyses were performed to assess the diagnostic performance of
      conventional ultrasound (US) and ARFI imaging in papillary thyroid microcarcinoma
      (PTMC). The independent risk factors for predicting PTMC were evaluated. RESULTS:
      The mean SWV value of benign and malignant thyroid nodules were 2.57 +/- 0.79 m/s
      (range: 0.90-4.92 m/s) and 3.88 +/- 2.24 m/s (range: 1.49-9.00 m/s) (P = 0.000).
      Az for VTI elastography score was higher than that for hypoechoic, absence of
      halo sign, and type III vascularity (P < 0.05). The optimal cut-offs for VTI
      elastography score and SWV were score 4 and 3.10 m/s. Gender, hypoechoic, taller
      than wide, VTI elastography score >= 4, and SWV > 3.10 m/s had been found to be
      independent risk factors for predicting PTMC. CONCLUSION: ARFI elastography can
      provide elasticity information of PTMC quantitatively (VTQ) and directly reflects
      the overall elastic properties (VTI). Gender, hypoechogenicity, taller than wide,
      VTI elastography score >= 4, and SWV > 3.10 m/s are independent risk factors for
      predicting PTMC. ARFI elastography seems to be a new tool for the diagnosis of
      PTMC.

PMID- 25045674
TI  - An investigation of small GTPases in relation to liver tumorigenesis using
      traditional Chinese medicine.
AB  - Recently, an important topic of liver tumorigenesis had been published in 2013.
      In this report, Ras and Rho had defined the relation of liver tumorigenesis. The
      traditional Chinese medicine (TCM) database has been screened for molecular
      compounds by simulating molecular docking and molecular dynamics to regulate Ras
      and liver tumorigenesis. Saussureamine C, S-allylmercaptocysteine, and Tryptophan
      are selected based on the highest docking score than other TCM compounds. The
      molecular dynamics are helpful in the analysis and detection of protein-ligand
      interactions. Based on the docking poses, hydrophobic interactions, and hydrogen
      bond variations, this research surmises are the main regions of important amino
      acids in Ras. In addition to the detection of TCM compound efficacy, we suggest
      Saussureamine C is better than the others for protein-ligand interaction. 

PMID- 25045675
TI  - Asymmetric cell division in polyploid giant cancer cells and low eukaryotic
      cells.
AB  - Asymmetric cell division is critical for generating cell diversity in low
      eukaryotic organisms. We previously have reported that polyploid giant cancer
      cells (PGCCs) induced by cobalt chloride demonstrate the ability to use an
      evolutionarily conserved process for renewal and fast reproduction, which is
      normally confined to simpler organisms. The budding yeast, Saccharomyces
      cerevisiae, which reproduces by asymmetric cell division, has long been a model
      for asymmetric cell division studies. PGCCs produce daughter cells asymmetrically
      in a manner similar to yeast, in that both use budding for cell polarization and
      cytokinesis. Here, we review the results of recent studies and discuss the
      similarities in the budding process between yeast and PGCCs. 

PMID- 25045676
TI  - Protective role of omega-3 polyunsaturated fatty acid against lead acetate
      induced toxicity in liver and kidney of female rats.
AB  - The present study was conducted to investigate the protective role of Omega-3
      polyunsaturated fatty acids against lead acetate-induced toxicity in liver and
      kidney of female rats. Animals were divided into four equal groups; group 1
      served as control while groups 2 and 3 were treated orally with Omega-3 fatty
      acids at doses of 125 and 260 mg/kg body weight, respectively, for 10 days. These
      groups were also injected with lead acetate (25 mg/kg body weight) during the
      last 5 days. Group 4 was treated only with lead acetate for 5 days and served as
      positive control group. Lead acetate increased oxidative stress through an
      elevation in MDA associated with depletion in antioxidant enzymes activities in
      the tissues. Moreover, the elevation of serum enzymes activities (ALT, AST, ALP,
      and LDH) and the levels of urea and creatinine were estimated but total proteins
      were decreased. Also, lead acetate-treatment induced hyperlipidemia via
      increasing of lipid profiles associated with decline in HDL-c level. Significant
      changes of Hb, PCV, RBCs, PLT, and WBCs in group 4 were recorded. The biochemical
      alterations of lead acetate were confirmed by histopathological changes and DNA
      damage. The administration of Omega-3 provided significant protection against
      lead acetate toxicity.

PMID- 25045677
TI  - Big data analytics in immunology: a knowledge-based approach.
AB  - With the vast amount of immunological data available, immunology research is
      entering the big data era. These data vary in granularity, quality, and
      complexity and are stored in various formats, including publications, technical
      reports, and databases. The challenge is to make the transition from data to
      actionable knowledge and wisdom and bridge the knowledge gap and application gap.
      We report a knowledge-based approach based on a framework called KB-builder that
      facilitates data mining by enabling fast development and deployment of web
      accessible immunological data knowledge warehouses. Immunological knowledge
      discovery relies heavily on both the availability of accurate, up-to-date, and
      well-organized data and the proper analytics tools. We propose the use of
      knowledge-based approaches by developing knowledgebases combining well-annotated
      data with specialized analytical tools and integrating them into analytical
      workflow. A set of well-defined workflow types with rich summarization and
      visualization capacity facilitates the transformation from data to critical
      information and knowledge. By using KB-builder, we enabled streamlining of
      normally time-consuming processes of database development. The knowledgebases
      built using KB-builder will speed up rational vaccine design by providing
      accurate and well-annotated data coupled with tailored computational analysis
      tools and workflow. 

PMID- 25045678
TI  - Increased release time of antibiotics from bone allografts through a novel
      biodegradable coating.
AB  - The use of bone allografts is contraindicated in septic revision surgery due to
      the high risk of graft reinfection. Antibiotic release from the graft may solve
      the problem and these combinations can theoretically be used for prevention or
      even therapy of infection. The present study investigated whether amoxicillin,
      ciprofloxacin, and vancomycin alone or in combination with chitosan or alginate
      are suitable for short-term or long-term bone coating. Human bone allografts were
      prepared from femoral head and lyophilized. Antibiotic coating was achieved by
      incubating the grafts in antibiotic solution and freeze-drying again. Two
      biopolymers chitosan and alginate were used for creating sustained-release
      implantable coatings and the drug release profile was characterized in vitro by
      spectrophotometry. Using lyophilization with or without chitosan only resulted in
      short-term release that lasted up to 48 hours. Alginate coating enabled a
      sustained release that lasted for 8 days with amoxicillin, 28 days with
      ciprofloxacin coating, and 50 days with vancomycin coating. Using only
      implantable biodegradable allograft and polymers, a sustained release of
      antibiotics was achieved with ciprofloxacin and vancomycin for several weeks.
      Since the calculated daily release of the antibiotic was lower than the
      recommended IV dose, the calcium alginate coated bone graft can support
      endoprosthesis revision surgery. 

PMID- 25045679
TI  - The study of naphthoquinones and their complexes with DNA by using Raman
      spectroscopy and surface enhanced Raman spectroscopy: new insight into
      interactions of DNA with plant secondary metabolites.
AB  - Naphthoquinones represent the group of plant secondary metabolites with cytotoxic
      properties based on their ability to generate reactive oxygen species and
      interfere with the processes of cell respiration. Due to this fact, the possible
      cytotoxic mechanisms on cellular and subcellular levels are investigated
      intensively. There are many targets of cytotoxic action on the cellular level;
      however, DNA is a critical target of many cytotoxic compounds. Due to the
      cytotoxic properties of naphthoquinones, it is necessary to study the processes
      of naphthoquinones, DNA interactions (1,4-naphthoquinone, binapthoquinone,
      juglone, lawsone, plumbagin), especially by using modern analytical techniques.
      In our work, the Raman spectroscopy was used to determine the possible binding
      sites of the naphthoquinones on the DNA and to characterize the bond of
      naphthoquinone to DNA. Experimental data reveals the relationships between the
      perturbations of structure-sensitive Raman bands and the types of the
      naphthoquinones involved. The modification of DNA by the studied naphthoquinones
      leads to the nonspecific interaction, which causes the transition of B-DNA into A
      DNA conformation. The change of the B-conformation of DNA for all measured DNA
      modified by naphthoquinones except plumbagin is obvious. 

PMID- 25045680
TI  - Shock absorbing function study on denucleated intervertebral disc with or without
      hydrogel injection through static and dynamic biomechanical tests in vitro.
AB  - Hydrogel injection has been recently proposed as a novel therapy for disc
      degenerative diseases, with the potential to restore the spine motion and the
      intervertebral disc height. However, it remains unknown whether the new technique
      could also maintain the shock absorbing property of the treated intervertebral
      disc. In this study, 18 porcine lumbar bone-disc-bone specimens were collected
      and randomly divided into three groups: the normal with intact intervertebral
      discs, the mimic for the injection of disulfide cross-linked hyaluronan hydrogels
      following discectomy, and the control disc with discectomy only. In the static
      compression test, specimens in the mimic group exhibited displacements similar to
      those in the normal discs, whereas the control group showed a significantly
      larger displacement range in the first two steps (P < 0.05). With the frequency
      increasing, all specimens generally displayed an increasing storage modulus,
      decreasing loss modulus, and tandelta. At any frequency point, the control group
      exhibited the largest value in all the three parameters among three groups while
      the normal group was the lowest, with the mimic group being mostly close to the
      normal group. Therefore, the hydrogel injection into the intervertebral discs
      greatly restored their shock absorbing function, suggesting that the technique
      could serve as an effective approach to maintaining biomechanical properties of
      the degenerative intervertebral disc. 

PMID- 25045682
TI  - Novel drugs development for cardio-/cerebrovascular diseases.

PMID- 25045681
TI  - Adenylyl cyclase signaling in the developing chick heart: the deranging effect of
      antiarrhythmic drugs.
AB  - The adenylyl cyclase (AC) signaling system plays a crucial role in the regulation
      of cardiac contractility. Here we analyzed the key components of myocardial AC
      signaling in the developing chick embryo and assessed the impact of selected beta
      blocking agents on this system. Application of metoprolol and carvedilol, two
      commonly used beta-blockers, at embryonic day (ED) 8 significantly downregulated
      (by about 40%) expression levels of AC5, the dominant cardiac AC isoform, and the
      amount of Gsalpha protein at ED9. Activity of AC stimulated by forskolin was also
      significantly reduced under these conditions. Interestingly, when administered at
      ED4, these drugs did not produce such profound changes in the myocardial AC
      signaling system, except for markedly increased expression of Gialpha protein.
      These data indicate that beta-blocking agents can strongly derange AC signaling
      during the first half of embryonic heart development. 

PMID- 25045683
TI  - Denture-related stomatitis is associated with endothelial dysfunction.
AB  - Oral inflammation, such as periodontitis, can lead to endothelial dysfunction,
      accelerated atherosclerosis, and vascular dysfunction. The relationship between
      vascular dysfunction and other common forms of oral infections such as denture
      related stomatitis (DRS) is unknown. Similar risk factors predispose to both
      conditions including smoking, diabetes, age, and obesity. Accordingly, we aimed
      to investigate endothelial function and major vascular disease risk factors in 44
      consecutive patients with dentures with clinical and microbiological features of
      DRS (n = 20) and without DRS (n = 24). While there was a tendency for higher
      occurrence of diabetes and smoking, groups did not differ significantly in
      respect to major vascular disease risk factors. Groups did not differ in main
      ambulatory blood pressure, total cholesterol, or even CRP. Importantly, flow
      mediated dilatation (FMD) was significantly lower in DRS than in non-DRS
      subjects, while nitroglycerin induced vasorelaxation (NMD) or intima-media
      thickness (IMT) was similar. Interestingly, while triglyceride levels were normal
      in both groups, they were higher in DRS subjects, although they did not correlate
      with either FMD or NMD. CONCLUSIONS: Denture related stomatitis is associated
      with endothelial dysfunction in elderly patients with dentures. This is in part
      related to the fact that diabetes and smoking increase risk of both DRS and
      cardiovascular disease.

PMID- 25045684
TI  - Measurement of hand/handrim grip forces in two different one arm drive
      wheelchairs.
AB  - PURPOSE: The aim of this study was to explore the total and regional grip forces
      in the hand when propelling two different manual one arm drive wheelchairs: the
      Neater Uni-wheelchair (NUW) and a foot steered Action3 wheelchair. METHODS: 17
      nondisabled users were randomly assigned to each wheelchair to drive around an
      indoor obstacle course. The Grip, a multiple sensor system taking continuous
      measurement of handgrip force, was attached to the propelling hand. Total grip
      force in each region of the hand and total grip force across the whole hand were
      calculated per user per wheelchair. RESULTS: The Action3 with foot steering only
      generated significantly greater total grip force in straight running compared to
      the NUW and also in the fingers and thumb in straight running. CONCLUSIONS: The
      results suggest that the Action3 with foot steering generated greater grip forces
      which may infer a greater potential for repetitive strain injury in the upper
      limb. Further work is required to explore whether the difference in grip force is
      of clinical significance in a disabled population.

PMID- 25045685
TI  - New advances in reproductive biomedicine.

PMID- 25045687
TI  - Subchondral bone plate thickening precedes chondrocyte apoptosis and cartilage
      degradation in spontaneous animal models of osteoarthritis.
AB  - Osteoarthritis (OA) is the most common joint disorder characterised by bone
      remodelling and cartilage degradation and associated with chondrocyte apoptosis.
      These processes were investigated at 10, 16, 24, and 30 weeks in Dunkin Hartley
      (DH) and Bristol Strain 2 (BS2) guinea pigs that develop OA spontaneously. Both
      strains had a more pronounced chondrocyte apoptosis, cartilage degradation, and
      subchondral bone changes in the medial than the lateral side of the tibia, and
      between strains, the changes were always greater and faster in DH than BS2. In
      the medial side, a significant increase of chondrocyte apoptosis and cartilage
      degradation was observed in DH between 24 and 30 weeks of age preceded by a
      progressive thickening and stiffening of subchondral bone plate (Sbp). The Sbp
      thickness consistently increased over the 30-week study period but the bone
      mineral density (BMD) of the Sbp gradually decreased after 16 weeks. The absence
      of these changes in the medial side of BS2 may indicate that the Sbp of DH was
      undergoing remodelling. Chondrocyte apoptosis was largely confined to the deep
      zone of articular cartilage and correlated with thickness of the subchondral bone
      plate suggesting that cartilage degradation and chondrocyte apoptosis may be a
      consequence of continuous bone remodelling during the development of OA in these
      animal models of OA. 

PMID- 25045688
TI  - Osteoblast-like cell behavior on porous scaffolds based on poly(styrene) fibers.
AB  - Scaffolds of nonresorbable biomaterials can represent an interesting alternative
      for replacing large bone defects in some particular clinical cases with massive
      bone loss. Poly(styrene) microfibers were prepared by a dry spinning method. They
      were partially melted to provide 3D porous scaffolds. The quality of the material
      was assessed by Raman spectroscopy. Surface roughness was determined by atomic
      force microscopy and vertical interference microscopy. Saos-2 osteoblast-like
      cells were seeded on the surface of the fibers and left to proliferate. Cell
      morphology, evaluated by scanning electron microscopy, revealed that they can
      spread and elongate on the rough microfiber surface. Porous 3D scaffolds made of
      nonresorbable poly(styrene) fibers are cytocompatible biomaterials mimicking
      allogenic bone trabeculae and allowing the growth and development of osteoblast
      like cells in vitro. 

PMID- 25045686
TI  - Molecular chaperones, cochaperones, and ubiquitination/deubiquitination system:
      involvement in the production of high quality spermatozoa.
AB  - Spermatogenesis is a complex process in which mitosis, meiosis, and cell
      differentiation events coexist. The need to guarantee the production of
      qualitatively functional spermatozoa has evolved into several control systems
      that check spermatogenesis progression/sperm maturation and tag aberrant gametes
      for degradation. In this review, we will focus on the importance of the
      evolutionarily conserved molecular pathways involving molecular chaperones
      belonging to the superfamily of heat shock proteins (HSPs), their cochaperones,
      and ubiquitination/deubiquitination system all over the spermatogenetic process.
      In this respect, we will discuss the conserved role played by the DNAJ protein
      Msj-1 (mouse sperm cell-specific DNAJ first homologue) and the deubiquitinating
      enzyme Ubpy (ubiquitin-specific processing protease-y) during the spermiogenesis
      in both mammals and nonmammalian vertebrates. 

PMID- 25045689
TI  - Drug release kinetics and front movement in matrix tablets containing diltiazem
      or metoprolol/lambda-carrageenan complexes.
AB  - In this work we investigated the moving boundaries and the associated drug
      release kinetics in matrix tablets prepared with two complexes between lambda
      carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol
      tartrate aiming at clarifying the role played by drug/polymer interaction on the
      water uptake, swelling, drug dissolution, and drug release performance of the
      matrix. The two studied complexes released the drug with different mechanism
      indicating two different drug/polymer interaction strengths. The comparison
      between the drug release behaviour of the complexes and the relevant physical
      mixtures indicates that diltiazem gave rise to a less soluble and more stable
      complex with carrageenan than metoprolol. The less stable metoprolol complex
      afforded an erodible matrix, whereas the stronger interaction between diltiazem
      and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was
      concluded that the different stability of the studied complexes affords two
      distinct drug delivery systems: in the case of MTP, the dissociation of the
      complex, as a consequence of the interaction with water, affords a classical
      soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing
      species is the complex itself because of the very strong interaction between the
      drug and the polymer. 

PMID- 25045690
TI  - VO2 kinetics and metabolic contributions whilst swimming at 95, 100, and 105% of
      the velocity at VO2max.
AB  - A bioenergetical analysis of swimming at intensities near competitive distances
      is inexistent. It was aimed to compare the transient VO2 kinetics responses and
      metabolic contributions whilst swimming at different velocities around VO2max. 12
      trained male swimmers performed (i) an incremental protocol to determine the
      velocity at VO2max (vVO2max) and (ii) three square wave exercises from rest to
      95, 100, and 105% of vVO2max. VO2 was directly measured using a telemetric
      portable gas analyser and its kinetics analysed through a double-exponential
      model. Metabolic contributions were assessed through the sum of three energy
      components. No differences were observed in the fast component response (tau1-
      15, 18, and 16 s, A1--36, 34, and 37 mL . kg(-1) . min (-1), and Gain--32, 29,
      and 30 mL . min (-1) at 95, 100, and 105% of the vVO2max, resp.) but A2 was
      higher in 95 and 100% compared to 105% intensity (480.76 +/- 247.01, 452.18 +/-
      217.04, and 147.04 +/- 60.40 mL . min (-1), resp.). The aerobic energy
      contribution increased with the time sustained (83 +/- 5, 74 +/- 6, and 59 +/- 7%
      for 95, 100, and 105%, resp.). The adjustment of the cardiovascular and/or
      pulmonary systems that determine O2 delivery and diffusion to the exercising
      muscles did not change with changing intensity, with the exception of VO2 slow
      component kinetics metabolic profiles.

PMID- 25045691
TI  - Conformational B-cell epitopes prediction from sequences using cost-sensitive
      ensemble classifiers and spatial clustering.
AB  - B-cell epitopes are regions of the antigen surface which can be recognized by
      certain antibodies and elicit the immune response. Identification of epitopes for
      a given antigen chain finds vital applications in vaccine and drug research.
      Experimental prediction of B-cell epitopes is time-consuming and resource
      intensive, which may benefit from the computational approaches to identify B-cell
      epitopes. In this paper, a novel cost-sensitive ensemble algorithm is proposed
      for predicting the antigenic determinant residues and then a spatial clustering
      algorithm is adopted to identify the potential epitopes. Firstly, we explore
      various discriminative features from primary sequences. Secondly, cost-sensitive
      ensemble scheme is introduced to deal with imbalanced learning problem. Thirdly,
      we adopt spatial algorithm to tell which residues may potentially form the
      epitopes. Based on the strategies mentioned above, a new predictor, called CBEP
      (conformational B-cell epitopes prediction), is proposed in this study. CBEP
      achieves good prediction performance with the mean AUC scores (AUCs) of 0.721 and
      0.703 on two benchmark datasets (bound and unbound) using the leave-one-out cross
      validation (LOOCV). When compared with previous prediction tools, CBEP produces
      higher sensitivity and comparable specificity values. A web server named CBEP
      which implements the proposed method is available for academic use. 

PMID- 25045692
TI  - Formulation optimization of erythromycin solid lipid nanocarrier using response
      surface methodology.
AB  - In present work response surface methodology (RSM) using the miscellaneous design
      model was used to optimize formulations of erythromycin solid lipid nanocarriers
      (ERY-SLN). Two-factor three level factorial design was considered for
      optimization. There were three parameters, drug entrapment efficiency (EE), drug
      loading (DL) percentage, and mean particle size of ERY-SLN, considered for
      investigating the optimal formulation with respect to two independent variables,
      including lipid concentration (X1) and surfactant : cosurfactant ratio (X2). The
      result showed that the optimal ERY-SLN was composed of lipid concentration (X1)
      15 mg/mL and surfactant : cosurfactant ratio (X2) 1 : 1 with %EE of 88.40 +/-
      2.09%, DL of 29.46 +/- 0.69%, mean particle size of 153.21 +/- 2.31 nm,
      polydispersity index (PDI) of 0.026 +/- 0.008, and zeta potential value of -15.18
      +/- (-5.53) mV. DSC and TEM study showed that there was no chemical interaction
      between ERY and lipid (GMS) and the ERY-SLN particles are nonspherical,
      respectively. The drug release experiments exhibited a sustained release over
      during 24 h, up to 66.26 +/- 2.83%. Accelerated stability studies showed that
      there was no significant change occurring in the responses after storage
      condition for a total period of 3 months.

PMID- 25045693
TI  - Liposomal formulation of turmerone-rich hexane fractions from Curcuma longa
      enhances their antileishmanial activity.
AB  - Promastigote forms of Leishmania amazonensis were treated with different
      concentrations of two fractions of Curcuma longa cortex rich in turmerones and
      their respective liposomal formulations in order to evaluate growth inhibition
      and the minimal inhibitory concentration (MIC). In addition, cellular alterations
      of treated promastigotes were investigated under transmission and scanning
      electron microscopies. LipoRHIC and LipoRHIWC presented lower MIC, 5.5 and 12.5
      MUg/mL, when compared to nonencapsulated fractions (125 and 250 MUg/mL),
      respectively, and to ar-turmerone (50 MUg/mL). Parasite growth inhibition was
      demonstrated to be dose-dependent. Important morphological changes as rounded
      body and presence of several roles on plasmatic membrane could be seen on L.
      amazonensis promastigotes after treatment with subinhibitory concentration (2.75
      MUg/mL) of the most active LipoRHIC. In that sense, the hexane fraction from the
      turmeric cortex of Curcuma longa incorporated in liposomal formulation (LipoRHIC)
      could represent good strategy for the development of new antileishmanial agent.

PMID- 25045694
TI  - Postmastectomy radiotherapy for locally advanced breast cancer receiving
      neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer
      (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is
      strongly debated. The aim of our analysis was to identify major prognostic
      factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170
      patients were treated with NAC and mastectomy at our center; 98 cases (57.6%)
      underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow
      up period of 7.7 years (range 2-16) for the whole cohort, median time to
      locoregional recurrence (LRR) was 3.3 years (range 0.7-12.4). The 5-year and 10
      year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate
      analysis the factors that significantly correlated with survival outcome were >=
      4 positive nodes (HR 5.0, 1.51-16.52; P = 0.035), extracapsular extension (HR
      2.18, 1.37-3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57,
      0.36-0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced
      LRR for patient with clinical T3 staged disease (P = 0.015). Our experience
      confirmed the impact of pathological nodal involvement on survival outcome. PMRT
      was found to improve local control in patients presenting with clinical T3
      tumors, regardless of the response to chemotherapy.

PMID- 25045695
TI  - A rat model of thrombosis in common carotid artery induced by implantable
      wireless light-emitting diode device.
AB  - This work has developed a novel approach to form common carotid artery (CCA)
      thrombus in rats with a wireless implantable light-emitting diode (LED) device.
      The device mainly consists of an external controller and an internal LED
      assembly. The controller was responsible for wirelessly transmitting electrical
      power. The internal LED assembly served as an implant to receive the power and
      irradiate light on CCA. The thrombus formation was identified with animal
      sonography, 7 T magnetic resonance imaging, and histopathologic examination. The
      present study showed that a LED assembly implanted on the outer surface of CCA
      could induce acute occlusion with single irradiation with 6 mW/cm(2) LED for 4 h.
      If intermittent irradiation with 4.3-4.5 mW/cm(2) LED for 2 h was shut off for 30
      min, then irradiation for another 2 h was applied; the thrombus was observed to
      grow gradually and was totally occluded at 7 days. Compared with the
      contralateral CCA without LED irradiation, the arterial endothelium in the LED
      irradiated artery was discontinued. Our study has shown that, by adjusting the
      duration of irradiation and the power intensity of LED, it is possible to produce
      acute occlusion and progressive thrombosis, which can be used as an animal model
      for antithrombotic drug development.

PMID- 25045696
TI  - Identification of phenolic acids and flavonoids in monofloral honey from
      Bangladesh by high performance liquid chromatography: determination of
      antioxidant capacity.
AB  - The aim of the present study was to characterize the phenolic acids, flavonoids,
      and antioxidant properties of monofloral honey collected from five different
      districts in Bangladesh. A new high performance liquid chromatography (HPLC)
      equipped with a UV detector method was developed for the identification of the
      phenolic acids and flavonoids. A total of five different phenolic acids were
      identified, with the most abundant being caffeic acid, benzoic acid, gallic acid,
      followed by chlorogenic acid and trans-cinnamic acid. The flavonoids, kaempferol,
      and catechin were most abundant, followed by myricetin and naringenin. The mean
      moisture content, total sugar content, and color characteristics of the honey
      samples were 18.36 +/- 0.95%, 67.40 +/- 5.63 g/100 g, and 129.27 +/- 34.66 mm
      Pfund, respectively. The mean total phenolic acids, total flavonoid content, and
      proline content were 199.20 +/- 135.23, 46.73 +/- 34.16, and 556.40 +/- 376.86
      mg/kg, respectively, while the mean FRAP values and DPPH radical scavenging
      activity were 327.30 +/- 231.87 MUM Fe (II)/100 g and 36.95 +/- 20.53%,
      respectively. Among the different types of honey, kalijira exhibited the highest
      phenolics and antioxidant properties. Overall, our study confirms that all the
      investigated honey samples are good sources of phenolic acids and flavonoids with
      good antioxidant properties.

PMID- 25045697
TI  - Electroacupuncture at ST36-ST37 and at ear ameliorates hippocampal mossy fiber
      sprouting in kainic acid-induced epileptic seizure rats.
AB  - Our previous study showed that mossy fiber sprouting can occur in the hippocampus
      region in rats 6 wk after kainic acid-induced epileptic seizure, and this mossy
      fiber sprouting can facilitate epileptogenesis. Transcutaneous auricular vagal
      nerve stimulation (VNS), which is similar to cervical VNS, can reduce the
      occurrence of epileptic seizure in intractable epilepsy patients. Greater
      parasympathetic nerve activity can be caused by 2 Hz electroacupuncture (EA).
      Therefore, we investigated the effect of 2 Hz EA at ST-36-ST37 and at the ear on
      mossy fiber sprouting in kainic-treated Sprague-Dawley rats. The results
      indicated that applying 2 Hz EA at ST36-ST37 and at the ear for 3 d per week over
      6 consecutive weeks can ameliorate mossy fiber sprouting in the hippocampus
      region of rats. These results indicated that applying 2 Hz EA at ST36-ST37 and at
      the ear might be beneficial for the treatment and prevention of epilepsy in
      humans.

PMID- 25045698
TI  - Possible inhibitor from traditional Chinese medicine for the beta form of calcium
      dependent protein kinase type II in the treatment of major depressive disorder.
AB  - Recently, an important topic of major depressive disorder (MDD) had been
      published in 2013. MDD is one of the most prevalent and disabling mental
      disorders. Consequently, much research is being undertaken into the causes and
      treatment. It has been found that inhibition of the beta form of
      calcium/calmodulin-dependent protein kinase type II (beta-CaMKII) can ameliorate
      the disorder. Upon screening the traditional Chinese medicine (TCM) database by
      molecular docking, sengesterone, labiatic acid, and methyl 3-O-feruloylquinate
      were selected for molecular dynamics. After 20 ns simulation, the RMSD, total
      energy, and structure variation could define the protein-ligand interaction.
      Furthermore, sengesterone, the principle candidate compound, has been found to
      have an effect on the regulation of emotions and memory development. In structure
      variation, we find the sample functional group of important amino acids make the
      protein stable and have limited variation. Due to similarity of structure
      variations, we suggest that these compounds may have an effect on beta-CaMKII and
      that sengesterone may have a similar efficacy as the control. However labiatic
      acid may be a stronger inhibitor of beta-CaMKII based on the larger RMSD and
      variation.

PMID- 25045699
TI  - Evaluation of antibacterial, antifungal, and antioxidant activities of safflower
      natural dyes during flowering.
AB  - Two Carthamus tinctorius varieties (Jawhara and 104) were studied in order to
      investigate their natural dyes contents and biological activities. Obtained
      results showed that quinochalcone contents and antioxidant activities varied
      considerably as function of flowering stages. So flowers at fructification stage
      contained the highest carthamin content with the strongest antioxidant capacity
      with all assays (FRAP, DPPH, and chelating power methods). In parallel, we showed
      a decrease in the content of precarthamin. The quantitative variation of these
      molecules could be due to colour change of C. tinctorius flowers. Correlation
      analysis indicated that the ABTS method showed the highest correlation
      coefficients with carthamin and precarthamin contents, that is, 0.886 and 0.973,
      respectively. Concerning the regional effect, the contents of precarthamin and
      carthamin varied significantly (P < 0.05) at studied regions with the optimum
      production given by samples of Beja (902.41 MUg/g DW and 42.05 MUg/g DW,
      respectively, at flowering stage). During flowering, the antimicrobial activity
      of these two natural dyes increased where the maximum inhibitory effect mentioned
      with carthamin mainly against E. coli (iz = 25.89 mm) at fructification stage.
      Therefore, the increased frequency of resistance to commonly used antibiotics
      leads to the search for new effective natural drugs at food and pharmaceutical
      industries.

PMID- 25045701
TI  - Are mood and anxiety disorders and alexithymia associated with endometriosis? A
      preliminary study.
AB  - OBJECTIVE: The aim of this preliminary study was to determine whether psychiatric
      disorders, psychopathological symptoms, and alexithymia are associated with
      endometriosis in an Italian population. STUDY DESIGN: A preliminary study
      comprising 37 Italian patients with surgically confirmed endometriosis and 43
      controls, without clinical and ultrasound signs of endometriosis, was carried
      out. Both patients and controls were evaluated for the presence/absence of
      psychiatric disorders, psychopathological symptoms, alexithymia, and pain
      symptoms (nonmenstrual pelvic pain, dysmenorrhea, and dyspareunia). RESULTS:
      Statistically significant differences were found between cases and controls for
      prevalence of mood and anxiety disorders, malfunctioning on obsessive-compulsive
      subscale (P < 0.01) and depression subscale (P < 0.05) of the Symptom Checklist
      90-Revisited (SCL-90-R), and higher alexithymia levels (P < 0.01). Patients with
      endometriosis-associated pain showed greater prevalence of psychiatric disorders
      compared to pain-free patients but that difference was not significant.
      Significant correlation was found between malfunctioning in some SCL-90-R
      dimensions and pelvic pain, dysmenorrhea, and dyspareunia scores at the visual
      analog score (VAS). CONCLUSION: Some psychopathological aspects, such as
      psychoemotional distress and alexithymia, are more frequent in women with
      endometriosis and might amplify pain symptoms in these patients.

PMID- 25045700
TI  - In silico investigation of traditional Chinese medicine compounds to inhibit
      human histone deacetylase 2 for patients with Alzheimer's disease.
AB  - Human histone deacetylase 2 (HDAC2) has been identified as being associated with
      Alzheimer's disease (AD), a neuropathic degenerative disease. In this study, we
      screen the world's largest Traditional Chinese Medicine (TCM) database for
      natural compounds that may be useful as lead compounds in the search for
      inhibitors of HDAC2 function. The technique of molecular docking was employed to
      select the ten top TCM candidates. We used three prediction models, multiple
      linear regression (MLR), support vector machine (SVM), and the Bayes network
      toolbox (BNT), to predict the bioactivity of the TCM candidates. Molecular
      dynamics simulation provides the protein-ligand interactions of compounds. The
      bioactivity predictions of pIC50 values suggest that the TCM candidatesm, (-)
      Bontl ferulate, monomethylcurcumin, and ningposides C, have a greater effect on
      HDAC2 inhibition. The structure variation caused by the hydrogen bonds and
      hydrophobic interactions between protein-ligand interactions indicates that these
      compounds have an inhibitory effect on the protein. 

PMID- 25045702
TI  - High prevalence of Panton-Valentine leukocidin (PVL) genes in nosocomial-acquired
      Staphylococcus aureus isolated from tertiary care hospitals in Nepal.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) carrying the important
      virulence determinant, Panton-Valentine leukocidin (PVL), is an emerging
      infectious pathogen associated with skin and soft tissue infections as well as
      life-threatening invasive diseases. In carrying out the first PVL prevalence
      study in Nepal, we screened 73 nosocomial isolates of S. aureus from 2 tertiary
      care Nepali hospitals and obtained an overall PVL-positivity rate of 35.6% among
      the hospital isolates: 26.1% of MRSA and 51.9% of methicillin sensitive S. aureus
      (MSSA) isolates were found to be positive for the PVL genes. PVL prevalence was
      not associated with a specific (i) infection site, (ii) age group, or (iii)
      hospital of origin. It was found to be positively associated with heterogeneous
      MRSA (73.3%) compared to homogeneous MRSA (3.2%) and MSSA (51.9%); negatively
      associated with multiresistant MRSA (22%) compared to nonmultiresistant MRSA
      (60%) and MSSA (51.9%); and positively associated with macrolide-streptogramin B
      resistance (93.8%) compared to macrolide-lincosamide-streptogramin B resistance
      (0%) and no-resistance (45.8%) types. Macrolide-streptogramin B resistance was
      confirmed by the presence of msr(A) gene. Restriction pattern analyses provided
      evidence to support the circulation of a limited number of clones of PVL-positive
      MRSA, arguing for the adaptability of these isolates to a hospital setting. 

PMID- 25045703
TI  - Drug design of cyclin-dependent kinase 2 inhibitor for melanoma from traditional
      Chinese medicine.
AB  - One has found an important cell cycle controller. This guard can decide the cell
      cycle toward proliferation or quiescence. Cyclin-dependent kinase 2 (CDK2) is a
      unique target among the CDK family in melanoma therapy. We attempted to find out
      TCM compounds from TCM Database@Taiwan that have the ability to inhibit the
      activity of CDK2 by systems biology. We selected Tetrahydropalmatine,
      Reserpiline, and (+)-Corydaline as the candidates by docking and screening
      results for further survey. We utilized support vector machine (SVM), multiple
      linear regression (MLR) models and Bayesian network for validation of predicted
      activity. By overall analysis of docking results, predicted activity, and
      molecular dynamics (MD) simulation, we could conclude that Tetrahydropalmatine,
      Reserpiline, and (+)-Corydaline had better binding affinity than the control. All
      of them had the ability to inhibit the activity of CDK2 and might have the
      opportunity to be applied in melanoma therapy. 

PMID- 25045705
TI  - Health care reform: understanding individuals' attitudes and information sources.
AB  - Since passage of the Affordable Care Act (ACA) was signed into law by President
      Barrack Obama, little is known about state-level perceptions of residents on the
      ACA. Perceptions about the act could potentially affect implementation of the law
      to the fullest extent. This 3-year survey study explored attitudes about the ACA,
      the types of information sources that individuals rely on when creating those
      attitudes, and the predictors of these attitudes among state of Indiana
      residents. The respondents were split between favorable and unfavorable views of
      the ACA, yet the majority of respondents strongly supported individual components
      of the act. National TV news, websites, family members, and individuals' own
      reading of the ACA legislation were identified as the most influential
      information sources. After controlling for potential confounders, the
      respondent's political affiliation, age, sex, and obtaining ACA information from
      watching national television news were the most important predictors of attitudes
      about the ACA and its components. These results mirror national-level findings.
      Implications for implementing health care reform at the state-level are
      discussed. 

PMID- 25045706
TI  - Impact of gentamicin coadministration along with high fructose feeding on
      progression of renal failure and metabolic syndrome in Sprague-Dawley rats.
AB  - The current study evaluates the impact of high fructose feeding in rat model of
      gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180-200 g were
      randomized into four groups; (C) received standard rodents chow with free access
      to ad libitum drinking water for 8 weeks and was considered as control, (F)
      received standard rodents chow with free access to drinking water supplemented
      with 20% (W/V) fructose for the same abovementioned period, (FG) was fed as group
      F and was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally
      during the last 20 days of the feeding period, and (G) was given gentamicin as
      above and fed as group C. Renal function was assessed at the end of the treatment
      period through measuring serum creatinine, uric acid and albumin, creatinine
      clearance, absolute and fractional excretion of both sodium and potassium, twenty
      four-hour urinary excretion of albumin, and renal histology. For metabolic
      syndrome assessment, fasting plasma glucose and insulin were measured and oral
      glucose tolerance test was performed throughout the treatment period. Results
      showed that gentamicin enhances progression of fructose induced metabolic
      syndrome. On the other hand, fructose pretreatment before gentamicin injection
      produced a comparable degree of renal dysfunction to those which were given
      fructose-free water but the picture of nephrotoxicity was somewhat altered as it
      was characterized by higher extent of glomerular congestion and protein urea.
      Overall, more vigilance is required when nephrotoxic drugs are prescribed for
      patients with fructose induced metabolic syndrome.

PMID- 25045704
TI  - We are ageing.
AB  - Ageing and longevity is unquestioningly complex. Several thoughts and mechanisms
      of ageing such as pathways involved in oxidative stress, lipid and glucose
      metabolism, inflammation, DNA damage and repair, growth hormone axis and insulin
      like growth factor (GH/IGF), and environmental exposure have been proposed. Also,
      some theories of ageing were introduced. To date, the most promising leads for
      longevity are caloric restriction, particularly target of rapamycin (TOR),
      sirtuins, hexarelin and hormetic responses. This review is an attempt to analyze
      the mechanisms and theories of ageing and achieving longevity. 

PMID- 25045707
TI  - [6]-Shogaol inhibits alpha-MSH-induced melanogenesis through the acceleration of
      ERK and PI3K/Akt-mediated MITF degradation.
AB  - [6]-Shogaol is the main biologically active component of ginger. Previous reports
      showed that [6]-shogaol has several pharmacological characteristics, such as
      antioxidative, anti-inflammatory, antimicrobial, and anticarcinogenic properties.
      However, the effects of [6]-shogaol on melanogenesis remain to be elucidated. The
      study aimed to evaluate the potential skin whitening mechanisms of [6]-shogaol.
      The effects of [6]-shogaol on cell viability, melanin content, tyrosinase
      activity, and the expression of the tyrosinase and microphthalmia-associated
      transcription factor (MITF) were measured. The results revealed that [6]-shogaol
      effectively suppresses tyrosinase activity and the amount of melanin and that
      those effects are more pronounced than those of arbutin. It was also found that
      [6]-shogaol decreased the protein expression levels of tyrosinase-related protein
      1 (TRP-1) and microphthalmia-associated transcriptional factor (MITF). In
      addition, the MITF mRNA levels were also effectively decreased in the presence of
      20 MUM [6]-shogaol. The degradation of MITF protein was inhibited by the MEK 1
      inhibitor (U0126) or phosphatidylinositol-3-kinase inhibitor (PI3K inhibitor)
      (LY294002). Further immunofluorescence staining assay implied the involvement of
      the proteasome in the downregulation of MITF by [6]-shogaol. Our confocal assay
      results also confirmed that [6]-shogaol inhibited alpha-melanocyte stimulating
      hormone- (alpha-MSH-) induced melanogenesis through the acceleration of
      extracellular responsive kinase (ERK) and phosphatidylinositol-3-kinase-
      (PI3K/Akt-) mediated MITF degradation.

PMID- 25045709
TI  - Regional warming and emerging vector-borne zoonotic dirofilariosis in the Russian
      Federation, Ukraine, and other post-Soviet states from 1981 to 2011 and
      projection by 2030.
AB  - We analyze through a climatic model the influence of regional warming on the
      geographical spreading and potential risk of infection of human dirofilariosis in
      Russia, Ukraine, and other post-Soviet states from 1981 to 2011 and estimate the
      situation by 2030. The model correctly predicts the spatiotemporal location of
      97.10% of 2154 clinical cases reported in the area during the studied period,
      identified by a retrospective review of the literature. There exists also a
      significant correlation between annual predicted Dirofilaria generations and
      calculated morbidity. The model states the progressive increase of 14.8% in the
      potential transmission area, up to latitude 64  degrees N, and 14.7% in
      population exposure. By 2030 an increase of 18.5% in transmission area and 10.8%
      in population exposure is expected. These findings strongly suggest the influence
      of global warming in both geographical spreading and increase in the number of
      Dirofilaria generations. The results should alert about the epidemiological
      behavior of dirofilariosis and other mosquito-borne diseases in these and other
      countries with similar climatic characteristics.

PMID- 25045708
TI  - An in vivo microdialysis study of FLZ penetration through the blood-brain barrier
      in normal and 6-hydroxydopamine induced Parkinson's disease model rats.
AB  - FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4
      hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a
      potential anti-Parkinson's disease (PD) agent. The objective of the present study
      was to investigate the penetration of free FLZ across the BBB and the effects of
      P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced
      PD model rats. In vivo microdialysis was used to collect FLZ containing brain and
      blood dialysates following intravenous (i.v.) drug administration either with or
      without pretreatment with the specific P-gp inhibitor, zosuquidar
      trihydrochloride (zosuquidar.3HCl). A sensitive, rapid, and reliable
      ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      technique was developed and validated to quantitate free FLZ levels in the
      dialysates. No significant differences were observed in the brain/blood FLZ area
      under the concentration-time curve (AUC) ratio between normal and PD model rats.
      However, pretreatment with zosuquidar.3HCl markedly increased the AUC ratio in
      both rat models. In addition, FLZ penetration was similar in zosuquidar.3HCl
      pretreated normal and PD rats. These results suggest that P-gp inhibition
      increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp
      normally restricts FLZ transfer to the brain. These findings could provide
      reference data for future clinical trials and may aid investigation of the BBB
      permeability of other CNS-active substances. 

PMID- 25045710
TI  - Insight into HIV of IFN-induced myxovirus resistance 2 (MX2) expressed by
      traditional Chinese medicine.
AB  - Recently, an important topic of the acquired immunodeficiency syndrome (AIDS) had
      been published in 2013. In this report, the expression of the IFN-induced
      myxovirus resistance 2 (MX2) had been defined the function to kill the human
      immunodeficiency virus (HIV). The screening from the Traditional Chinese Medicine
      (TCM) database by simulating molecular docking and molecular dynamics could
      select candidate compounds, which may express MX2 against HIV. Saussureamine C,
      Crotalaburnine, and Precatorine are selected based on the highest docking score
      and other TCM compounds. The data from molecular dynamics are helpful in the
      analysis and detection of protein-ligand interactions. According to the docking
      poses, hydrophobic interactions, and hydrogen bond with structure variations,
      this research could assess the interaction between protein and ligand
      interaction. In addition to the detection of TCM compound efficacy, we suggest
      that Saussureamine C is better than the others in protein-ligand interaction and
      the structural variation to express MX2. 

PMID- 25045711
TI  - Widespread 25-hydroxyvitamin D deficiency in affluent and nonaffluent pregnant
      Indian women.
AB  - OBJECTIVES: This cross-sectional study primarily aimed to assess vitamin D
      adequacy in the third trimester of pregnancy using 25-hydroxyvitamin D (25(OH)D)
      and explore lifestyle characteristics (sun exposure index, diet, and economic
      indicators) associated with serum 25(OH)D. The secondary aim was to examine the
      relationship of serum 25(OH)D with birth weight and gestational age. METHODS:
      Serum 25(OH)D was measured by chemiluminescent immunoassay in 150 pregnant women
      from Mumbai. Sun exposure index was computed. Dietary calcium, phytate : calcium
      ratio, and dietary phosphorus was calculated using the 24-hour diet recall
      method. RESULTS: All women had 25(OH)D levels < 30.00 ng/ml. Multivariable linear
      regression showed that nonaffluent women had poorer 25(OH)D status than their
      affluent counterparts (beta = -0.20; P = 0.03). Higher sun exposure index was
      associated with higher 25(OH)D concentrations (beta = 0.31; P < 0.001), which
      remained significant after controlling for covariates. At the bivariate level,
      mothers of infants weighing <2500 g had lower serum 25(OH)D concentrations
      compared to mothers whose infants weighed >= 2500 g (P = 0.02). This association
      became non-significant after controlling for covariates. CONCLUSIONS: Vitamin D
      deficiency was universally prevalent in the cohort studied. There is a need to
      develop culturally sensitive strategies for improving the 25(OH)D status.

PMID- 25045712
TI  - Multiple effects of berberine derivatives on colon cancer cells.
AB  - The pharmacological use of the plant alkaloid berberine is based on its
      antibacterial and anti-inflammatory properties; recently, anticancer activity has
      been attributed to this compound. To exploit this interesting feature, we
      synthesized three berberine derivatives, namely, NAX012, NAX014, and NAX018, and
      we tested their effects on two human colon carcinoma cell lines, that is, HCT116
      and SW613-B3, which are characterized by wt and mutated p53, respectively. We
      observed that cell proliferation is more affected by cell treatment with the
      derivatives than with the lead compound; moreover, the derivatives proved to
      induce cell cycle arrest and cell death through apoptosis, thus suggesting that
      they could be promising anticancer drugs. Finally, we detected typical signs of
      autophagy in cells treated with berberine derivatives. 

PMID- 25045713
TI  - Gradually increased training intensity benefits rehabilitation outcome after
      stroke by BDNF upregulation and stress suppression.
AB  - Physical training is necessary for effective rehabilitation in the early
      poststroke period. Animal studies commonly use fixed training intensity
      throughout rehabilitation and without adapting it to the animals' recovered motor
      ability. This study investigated the correlation between training intensity and
      rehabilitation efficacy by using a focal ischemic stroke rat model. Eighty male
      Sprague-Dawley rats were induced with middle cerebral artery
      occlusion/reperfusion surgery. Sixty rats with successful stroke were then
      randomly assigned into four groups: control (CG, n = 15), low intensity (LG, n =
      15), gradually increased intensity (GIG, n = 15), and high intensity (HG, n =
      15). Behavioral tests were conducted daily to evaluate motor function recovery.
      Stress level and neural recovery were evaluated via plasma corticosterone and
      brain-derived neurotrophic factor (BDNF) concentration, respectively. GIG rats
      significantly (P < 0.05) recovered motor function and produced higher hippocampal
      BDNF (112.87 +/- 25.18 ng/g). GIG and LG rats exhibited similar stress levels
      (540.63 +/- 117.40 nM/L and 508.07 +/- 161.30 nM/L, resp.), which were
      significantly lower (P < 0.05) than that (716.90 +/- 156.48 nM/L) of HG rats.
      Training with gradually increased intensity achieved better recovery with lower
      stress. Our observations indicate that a training protocol that includes
      gradually increasing training intensity should be considered in both animal and
      clinical studies for better stroke recovery.

PMID- 25045714
TI  - Comparative analysis of proliferation and differentiation potentials of stem
      cells from inflamed pulp of deciduous teeth and stem cells from exfoliated
      deciduous teeth.
AB  - Stem cells isolated from exfoliated deciduous teeth (SHEDs) are highly capable of
      proliferation and differentiation, and they represent good cell sources for
      mesenchymal stem cell- (MSC-) mediated dental tissue regeneration, but the supply
      of SHEDs is limited. A previous study found that stem cells could be isolated
      from inflamed tissues, but it is unknown whether primary dental pulp diagnosed
      with irreversible pulpitis might contain stem cells with appropriate tissue
      regeneration capacity. In this study, we aimed to isolate stem cells from both
      inflamed pulps of deciduous teeth (SCIDs) and SHEDs from Chinese children and to
      compare their proliferation and differentiation potentials. Our results showed
      that SCIDs were positive for cell surface markers, including CD105, CD90, and
      CD146, and they had high proliferation ability and osteogenic, adipogenic, and
      chondrogenic differentiation potentials. There was no significant difference in
      proliferation and differentiation potentials between SCIDs and SHEDs. The mRNA of
      inflammatory factors, including IL-1beta, IL-6, and TNF-alpha, was expressed at
      similar levels in SCIDs and SHEDs, but SCIDs secreted more TNF-alpha protein. In
      conclusion, our in vitro results showed that SCIDs have proliferation and
      differentiation potentials similar to those of SHEDs. Thus, SCIDs represent a new
      potentially applicable source for MSC mediated tissue regeneration. 

PMID- 25045715
TI  - Heart health risk assessment system: a nonintrusive proposal using ontologies and
      expert rules.
AB  - According to the World Health Organization, the world's leading cause of death is
      heart disease, with nearly two million deaths per year. Although some factors are
      not possible to change, there are some keys that help to prevent heart diseases.
      One of the most important keys is to keep an active daily life, with moderate
      exercise. However, deciding what a moderate exercise is or when a slightly
      abnormal heart rate value is a risk depends on the person and the activity. In
      this paper we propose a context-aware system that is able to determine the
      activity the person is performing in an unobtrusive way. Then, we have defined
      ontology to represent the available knowledge about the person (biometric data,
      fitness status, medical information, etc.) and her current activity (level of
      intensity, heart rate recommended for that activity, etc.). With such knowledge,
      a set of expert rules based on this ontology are involved in a reasoning process
      to infer levels of alerts or suggestions for the users when the intensity of the
      activity is detected as dangerous for her health. We show how this approach can
      be accomplished by using only everyday devices such as a smartphone and a
      smartwatch. 

PMID- 25045716
TI  - Parallel solutions for voxel-based simulations of reaction-diffusion systems.
AB  - There is an increasing awareness of the pivotal role of noise in biochemical
      processes and of the effect of molecular crowding on the dynamics of biochemical
      systems. This necessity has given rise to a strong need for suitable and
      sophisticated algorithms for the simulation of biological phenomena taking into
      account both spatial effects and noise. However, the high computational effort
      characterizing simulation approaches, coupled with the necessity to simulate the
      models several times to achieve statistically relevant information on the model
      behaviours, makes such kind of algorithms very time-consuming for studying real
      systems. So far, different parallelization approaches have been deployed to
      reduce the computational time required to simulate the temporal dynamics of
      biochemical systems using stochastic algorithms. In this work we discuss these
      aspects for the spatial TAU-leaping in crowded compartments (STAUCC) simulator, a
      voxel-based method for the stochastic simulation of reaction-diffusion processes
      which relies on the Stau-DPP algorithm. In particular we present how the
      characteristics of the algorithm can be exploited for an effective
      parallelization on the present heterogeneous HPC architectures. 

PMID- 25045717
TI  - The experimental and clinical aspects of beta cell function and its underlying
      mechanism.

PMID- 25045718
TI  - Generation of recombinant porcine parvovirus virus-like particles in
      Saccharomyces cerevisiae and development of virus-specific monoclonal antibodies.
AB  - Porcine parvovirus (PPV) is a widespread infectious virus that causes serious
      reproductive diseases of swine and death of piglets. The gene coding for the
      major capsid protein VP2 of PPV was amplified using viral nucleic acid extract
      from swine serum and inserted into yeast Saccharomyces cerevisiae expression
      plasmid. Recombinant PPV VP2 protein was efficiently expressed in yeast and
      purified using density gradient centrifugation. Electron microscopy analysis of
      purified PPV VP2 protein revealed the self-assembly of virus-like particles
      (VLPs). Nine monoclonal antibodies (MAbs) against the recombinant PPV VP2 protein
      were generated. The specificity of the newly generated MAbs was proven by
      immunofluorescence analysis of PPV-infected cells. Indirect IgG ELISA based on
      the recombinant VLPs for detection of PPV-specific antibodies in swine sera was
      developed and evaluated. The sensitivity and specificity of the new assay were
      found to be 93.4% and 97.4%, respectively. In conclusion, yeast S. cerevisiae
      represents a promising expression system for generating recombinant PPV VP2
      protein VLPs of diagnostic relevance. 

PMID- 25045719
TI  - Functional properties of CD8(+) lymphocytes in patients with pleural plaque and
      malignant mesothelioma.
AB  - It is known that asbestos exposure can cause malignant mesothelioma (MM) and that
      CD8(+) T cells play a critical role in antitumor immunity. We examined the
      properties of peripheral blood CD8(+) lymphocytes from asbestos-exposed patients
      with pleural plaque (PL) and MM. The percentage of CD3(+)CD8(+) cells in PBMCs
      did not differ among the three groups, although the total numbers of PBMCs of the
      PL and MM groups were lower than those of the healthy volunteers (HV). The
      percentage of IFN-gamma (+) and CD107a(+) cells in PMA/ionomycin-stimulated
      CD8(+) lymphocytes did not differ among the three groups. Percentages of
      perforin(+) cells and CD45RA(-) cells in fresh CD8(+) lymphocytes of PL and MM
      groups were higher than those of HV. Percentages of granzyme B(+) and perforin(+)
      cells in PMA/ionomycin-stimulated CD8(+) lymphocytes were higher in PL group
      compared with HV. The MM group showed a decrease of perforin level in CD8(+)
      lymphocytes after stimulation compared with patients with PL. These results
      indicate that MM patients have characteristics of impairment in stimulation
      induced cytotoxicity of peripheral blood CD8(+) lymphocytes and that PL and MM
      patients have a common character of functional alteration in those lymphocytes,
      namely, an increase in memory cells, possibly related to exposure to asbestos. 

PMID- 25045720
TI  - Faraday instability-based micro droplet ejection for inhalation drug delivery.
AB  - We report here the technology and the underlying science of a new device for
      inhalation (pulmonary) drug delivery which is capable of fulfilling needs unmet
      by current commercial devices. The core of the new device is a centimeter-size
      clog-free silicon-based ultrasonic nozzle with multiple Fourier horns in
      resonance at megahertz (MHz) frequency. The dramatic resonance effect among the
      multiple horns and high growth rate of the MHz Faraday waves excited on a
      medicinal liquid layer together facilitate ejection of monodisperse droplets of
      desirable size range (2-5 um) at low electrical drive power (<1.0 W). The small
      nozzle requiring low drive power has enabled realization of a pocket-size (8.6 *
      5.6 * 1.5 cm3) ultrasonic nebulizer. A variety of common pulmonary drugs have
      been nebulized using the pocket-size unit with desirable aerosol sizes and output
      rate. These results clearly provide proof-of-principle for the new device and
      confirm its potential for commercialization.

PMID- 25045721
TI  - Rapid ratiometric biomarker detection with topically applied SERS nanoparticles.
AB  - Multiplexed surface-enhanced Raman scattering (SERS) nanoparticles (NPs) offer
      the potential for rapid molecular phenotyping of tissues, thereby enabling
      accurate disease detection as well as patient stratification to guide
      personalized therapies or to monitor treatment outcomes. The clinical success of
      molecular diagnostics based on SERS NPs would be facilitated by the ability to
      accurately identify tissue biomarkers under time-constrained staining and
      detection conditions with a portable device. In vitro, ex vivo and in vivo
      experiments were performed to optimize the technology and protocols for the rapid
      detection (0.1-s integration time) of multiple cell-surface biomarkers with a
      miniature fiber-optic spectral-detection probe following a brief (5 min) topical
      application of SERS NPs on tissues. Furthermore, we demonstrate that the
      simultaneous detection and ratiometric quantification of targeted and nontargeted
      NPs allows for an unambiguous assessment of molecular expression that is
      insensitive to nonspecific variations in NP concentrations.

PMID- 25045722
TI  - The responses of the quantitative characteristics of a ramet population of the
      ephemeroid rhizomatous sedge Carex physodes to the moisture content of the soil
      in various locations on sand dunes.
AB  - In this study, the soil moisture content was measured, and the quantitative
      characteristics of this sedge species were compared. The phenotypic plasticity of
      each parameter and the linear regression relationships were analyzed. The results
      showed that the soil moisture content was significantly affected by location,
      soil depth, and sampling date. The aboveground biomass, underground biomass,
      biomass density, and population density at the peak were significantly higher
      than elsewhere on the dune. However, the morphological plasticity index of the
      quantitative characteristics was higher at the base and middle of the dune. When
      the soil moisture content decreased, the underground biomass and ramet biomass
      density increased. The aboveground and underground biomasses were strongly
      negatively correlated, but the ramet height and aboveground biomass were strongly
      positively correlated. These results indicated that the soil water content
      significantly affected the clonal growth of C. physodes. The responsiveness of C.
      physodes may be adaptive when the soil resource supply is low. The strong
      morphological plasticity of the species appears to be ecologically important for
      the maintenance and dominance of this species in the dune habitat. 

PMID- 25045723
TI  - An incus-body driving type piezoelectric middle ear implant design and evaluation
      in 3D computational model and temporal bone.
AB  - A new incus-body driving type transducer relying on piezoelectric stack, with
      broad frequency bandwidth, is proposed for use in a middle ear implant. To aid
      the design process of this transducer, a coupling biomechanical model of the
      human middle ear and the piezoelectric transducer was established by reverse
      engineering technology. The validity of this model was confirmed by comparing
      model predicted motions with experimental measurements. Based on this verified
      biomechanical model, the main parameters of the transducer were determined. And
      its power consumption was calculated. Finally, to verify the capability of the
      designed piezoelectric transducer, a human temporal bone experimental platform
      was built. And the dynamic characteristics and the stimulated performance of the
      piezoelectric transducer were tested. The result showed that stapes displacement
      stimulated by the transducer excitation at 10.5 V RMS was equivalent to that from
      acoustic stimulation at 100 dB SPL, which is an adequate stimulation to the
      ossicular chain. The corresponding power consumption is 0.31 mW per volt of
      excitation at 1 kHz, which is low enough for the transducer to be used in a
      middle ear implant. Besides, this transducer demonstrates high performance at
      high frequencies.

PMID- 25045724
TI  - Evaluation of skin permeation and analgesic activity effects of carbopol
      lornoxicam topical gels containing penetration enhancer.
AB  - The current study was designed to develop a topical gel formulation for improved
      skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity.
      Moreover, the effect of different penetration enhancers on LOR was studied. The
      LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC)
      and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol
      were developed. The formulated gels were characterized for pH, viscosity, and LOR
      release using Franz diffusion cells. Also, in vitro skin permeation of LOR was
      conducted. The effect of hydroxypropyl beta-cyclodextrin (HP beta-CD), beta
      cyclodextrin (beta-CD), Tween 80, and oleic acid on LOR permeation was evaluated.
      The optimized LOR gel formulation (LORF8) showed the highest flux (14.31
      MUg/cm(2)/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP
      beta-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly.
      It was observed that LORF3 and LORF8 show similar analgesic activity compared to
      marketed LOR injection (Xefo). This work shows that LOR can be formulated into
      carbopol gel in presence of PG and HP beta-CD and may be promising in enhancing
      permeation.

PMID- 25045725
TI  - Receiver diversity combining using evolutionary algorithms in Rayleigh fading
      channel.
AB  - In diversity combining at the receiver, the output signal-to-noise ratio (SNR) is
      often maximized by using the maximal ratio combining (MRC) provided that the
      channel is perfectly estimated at the receiver. However, channel estimation is
      rarely perfect in practice, which results in deteriorating the system
      performance. In this paper, an imperialistic competitive algorithm (ICA) is
      proposed and compared with two other evolutionary based algorithms, namely,
      particle swarm optimization (PSO) and genetic algorithm (GA), for diversity
      combining of signals travelling across the imperfect channels. The proposed
      algorithm adjusts the combiner weights of the received signal components in such
      a way that maximizes the SNR and minimizes the bit error rate (BER). The results
      indicate that the proposed method eliminates the need of channel estimation and
      can outperform the conventional diversity combining methods. 

PMID- 25045726
TI  - Comparing the effect of oral supplementation of vitamin E, injective vitamin E
      and selenium or both during late pregnancy on production and reproductive
      performance and immune function of dairy cows and calves.
AB  - The object of this study was to determine the effect of prepartum supplementation
      of vitamin E with or without injective vitamin E and selenium (Se) on productive
      and reproductive performances and immune function in dairy cows. Sixty
      multiparous Holstein dairy cows were divided randomly into three groups at the
      end of gestation. Cows in each group received one of three treatments: (1) a
      single intramuscular (im) injection of vit. E + selenium 3 weeks prepartum; (2)
      daily supplementation of oral vit. E given from 3 weeks prepartum to parturition;
      (3) injective vit. E + Se with daily supplementation of oral vit. E. Blood
      samples were collected from cows at calving and from calves at 0 and 7 days of
      age. Concentration of IgG in serum of cows and calves as well as in colostrum was
      determined. No significant differences among treatments occurred in the
      concentrations of IgG, animal, and calf production and reproduction performance.
      Due to the lack of significant difference between injection and oral
      supplementation, it is recommended to replace the injection with oral
      supplementation. 

PMID- 25045727
TI  - Efficient feature selection and classification of protein sequence data in
      bioinformatics.
AB  - Bioinformatics has been an emerging area of research for the last three decades.
      The ultimate aims of bioinformatics were to store and manage the biological data,
      and develop and analyze computational tools to enhance their understanding. The
      size of data accumulated under various sequencing projects is increasing
      exponentially, which presents difficulties for the experimental methods. To
      reduce the gap between newly sequenced protein and proteins with known functions,
      many computational techniques involving classification and clustering algorithms
      were proposed in the past. The classification of protein sequences into existing
      superfamilies is helpful in predicting the structure and function of large amount
      of newly discovered proteins. The existing classification results are
      unsatisfactory due to a huge size of features obtained through various feature
      encoding methods. In this work, a statistical metric-based feature selection
      technique has been proposed in order to reduce the size of the extracted feature
      vector. The proposed method of protein classification shows significant
      improvement in terms of performance measure metrics: accuracy, sensitivity,
      specificity, recall, F-measure, and so forth. 

PMID- 25045728
TI  - Regulating N application for rice yield and sustainable eco-agro development in
      the upper reaches of Yellow River basin, China.
AB  - High N fertilizer and flooding irrigation applied to rice on anthropogenic
      alluvial soil often result in N leaching and low recovery of applied fertilizer N
      from the rice fields in Ningxia irrigation region in the upper reaches of the
      Yellow River, which threatens ecological environment, food security, and
      sustainable agricultural development. This paper reported the regulating N
      application for rice yield and sustainable Eco-Agro development in the upper
      reaches of Yellow River basin. The results showed that reducing and postponing N
      application could maintain crop yields while substantially reducing N leaching
      losses to the environment and improving the nitrogen use efficiency. Considering
      the high food production, the minimum environmental threat, and the low labor
      input, we suggested that regulating N application is an important measure to help
      sustainable agricultural development in this region. 

PMID- 25045729
TI  - Design and experimental validation for direct-drive fault-tolerant permanent
      magnet vernier machines.
AB  - A fault-tolerant permanent-magnet vernier (FT-PMV) machine is designed for direct
      drive applications, incorporating the merits of high torque density and high
      reliability. Based on the so-called magnetic gearing effect, PMV machines have
      the ability of high torque density by introducing the flux-modulation poles
      (FMPs). This paper investigates the fault-tolerant characteristic of PMV machines
      and provides a design method, which is able to not only meet the fault-tolerant
      requirements but also keep the ability of high torque density. The operation
      principle of the proposed machine has been analyzed. The design process and
      optimization are presented specifically, such as the combination of slots and
      poles, the winding distribution, and the dimensions of PMs and teeth. By using
      the time-stepping finite element method (TS-FEM), the machine performances are
      evaluated. Finally, the FT-PMV machine is manufactured, and the experimental
      results are presented to validate the theoretical analysis. 

PMID- 25045730
TI  - Mechanistic features of nanodiamonds in the lapping of magnetic heads.
AB  - Nanodiamonds, which are the main components of slurry in the precision lapping
      process of magnetic heads, play an important role in surface quality. This paper
      studies the mechanistic features of nanodiamond embedment into a Sn plate in the
      lapping process. This is the first study to develop mathematical models for
      nanodiamond embedment. Such models can predict the optimum parameters for
      particle embedment. From the modeling calculations, the embedded pressure
      satisfies p 0 = (3/2) . (W/pia (2)) and the indentation depth satisfies delta =
      k1?P/HV. Calculation results reveal that the largest embedded pressure is 731.48
      GPa and the critical indentation depth delta is 7 nm. Atomic force microscopy
      (AFM), scanning electron microscopy (SEM), and Auger electron spectroscopy (AES)
      were used to carry out surface quality detection and analysis of the disk head.
      Both the formation of black spots on the surface and the removal rate have an
      important correlation with the size of nanodiamonds. The results demonstrate that
      an improved removal rate (21 nm . min(-1)) can be obtained with 100 nm diamonds
      embedded in the plate.

PMID- 25045731
TI  - Joint subchannel pairing and power control for cognitive radio networks with
      amplify-and-forward relaying.
AB  - Dynamic spectrum sharing has drawn intensive attention in cognitive radio
      networks. The secondary users are allowed to use the available spectrum to
      transmit data if the interference to the primary users is maintained at a low
      level. Cooperative transmission for secondary users can reduce the transmission
      power and thus improve the performance further. We study the joint subchannel
      pairing and power allocation problem in relay-based cognitive radio networks. The
      objective is to maximize the sum rate of the secondary user that is helped by an
      amplify-and-forward relay. The individual power constraints at the source and the
      relay, the subchannel pairing constraints, and the interference power constraints
      are considered. The problem under consideration is formulated as a mixed integer
      programming problem. By the dual decomposition method, a joint optimal subchannel
      pairing and power allocation algorithm is proposed. To reduce the computational
      complexity, two suboptimal algorithms are developed. Simulations have been
      conducted to verify the performance of the proposed algorithms in terms of sum
      rate and average running time under different conditions. 

PMID- 25045732
TI  - Static analysis of large-scale multibody system using joint coordinates and
      spatial algebra operator.
AB  - Initial transient oscillations inhibited in the dynamic simulations responses of
      multibody systems can lead to inaccurate results, unrealistic load prediction, or
      simulation failure. These transients could result from incompatible initial
      conditions, initial constraints violation, and inadequate kinematic assembly.
      Performing static equilibrium analysis before the dynamic simulation can
      eliminate these transients and lead to stable simulation. Most exiting multibody
      formulations determine the static equilibrium position by minimizing the system
      potential energy. This paper presents a new general purpose approach for solving
      the static equilibrium in large-scale articulated multibody. The proposed
      approach introduces an energy drainage mechanism based on Baumgarte constraint
      stabilization approach to determine the static equilibrium position. The spatial
      algebra operator is used to express the kinematic and dynamic equations of the
      closed-loop multibody system. The proposed multibody system formulation utilizes
      the joint coordinates and modal elastic coordinates as the system generalized
      coordinates. The recursive nonlinear equations of motion are formulated using the
      Cartesian coordinates and the joint coordinates to form an augmented set of
      differential algebraic equations. Then system connectivity matrix is derived from
      the system topological relations and used to project the Cartesian quantities
      into the joint subspace leading to minimum set of differential equations. 

PMID- 25045733
TI  - Enhanced performance by time-frequency-phase feature for EEG-based BCI systems.
AB  - We introduce a new motor parameter imagery paradigm using clench speed and clench
      force motor imagery. The time-frequency-phase features are extracted from mu
      rhythm and beta rhythms, and the features are optimized using three process
      methods: no-scaled feature using "MIFS" feature selection criterion, scaled
      feature using "MIFS" feature selection criterion, and scaled feature using "mRMR"
      feature selection criterion. Support vector machines (SVMs) and extreme learning
      machines (ELMs) are compared for classification between clench speed and clench
      force motor imagery using the optimized feature. Our results show that no
      significant difference in the classification rate between SVMs and ELMs is found.
      The scaled feature combinations can get higher classification accuracy than the
      no-scaled feature combinations at significant level of 0.01, and the "mRMR"
      feature selection criterion can get higher classification rate than the "MIFS"
      feature selection criterion at significant level of 0.01. The time-frequency
      phase feature can improve the classification rate by about 20% more than the time
      frequency feature, and the best classification rate between clench speed motor
      imagery and clench force motor imagery is 92%. In conclusion, the motor parameter
      imagery paradigm has the potential to increase the direct control commands for
      BCI control and the time-frequency-phase feature has the ability to improve BCI
      classification accuracy. 

PMID- 25045734
TI  - Parametric study on responses of a self-anchored suspension bridge to sudden
      breakage of a hanger.
AB  - The girder of self-anchored suspension bridge is subjected to large compression
      force applied by main cables. So, serious damage of the girder due to breakage of
      hangers may cause the collapse of the whole bridge. With the time increasing, the
      hangers may break suddenly for their resistance capacities decrease due to
      corrosion. Using nonlinear static and dynamic analysis methods and adopting 3D
      finite element model, the responses of an actual self-anchored suspension bridge
      to sudden breakage of hangers are studied in this paper. The results show that
      the sudden breakage of a hanger causes violent vibration and large changes in
      internal forces of the bridge. In the process of the vibration, the maximum
      tension of hanger produced by breakage of a hanger exceeds 2.22 times its initial
      value, and the reaction forces of the bearings increase by more than 1.86 times
      the tension of the broken hanger. Based on the actual bridge, the influences of
      some factors including flexural stiffness of girder, torsion stiffness of girder,
      flexural stiffness of main cable, weight of girder, weight of main cable, span to
      sag ratio of main cable, distance of hangers, span length, and breakage time of
      hanger on the dynamic responses are studied in detail, and the influencing extent
      of the factors is presented. 

PMID- 25045735
TI  - Introducing the MCHF/OVRP/SDMP: multicapacitated/heterogeneous fleet/open vehicle
      routing problems with split deliveries and multiproducts.
AB  - In this paper, we analyze a real-world OVRP problem for a production company.
      Considering real-world constrains, we classify our problem as
      multicapacitated/heterogeneous fleet/open vehicle routing problem with split
      deliveries and multiproduct (MCHF/OVRP/SDMP) which is a novel classification of
      an OVRP. We have developed a mixed integer programming (MIP) model for the
      problem and generated test problems in different size (10-90 customers)
      considering real-world parameters. Although MIP is able to find optimal solutions
      of small size (10 customers) problems, when the number of customers increases,
      the problem gets harder to solve, and thus MIP could not find optimal solutions
      for problems that contain more than 10 customers. Moreover, MIP fails to find any
      feasible solution of large-scale problems (50-90 customers) within time limits
      (7200 seconds). Therefore, we have developed a genetic algorithm (GA) based
      solution approach for large-scale problems. The experimental results show that
      the GA based approach reaches successful solutions with 9.66% gap in 392.8 s on
      average instead of 7200 s for the problems that contain 10-50 customers. For
      large-scale problems (50-90 customers), GA reaches feasible solutions of problems
      within time limits. In conclusion, for the real-world applications, GA is
      preferable rather than MIP to reach feasible solutions in short time periods.

PMID- 25045736
TI  - Assessment of the GHG reduction potential from energy crops using a combined LCA
      and biogeochemical process models: a review.
AB  - The main purpose for developing biofuel is to reduce GHG (greenhouse gas)
      emissions, but the comprehensive environmental impact of such fuels is not clear.
      Life cycle analysis (LCA), as a complete comprehensive analysis method, has been
      widely used in bioenergy assessment studies. Great efforts have been directed
      toward establishing an efficient method for comprehensively estimating the
      greenhouse gas (GHG) emission reduction potential from the large-scale
      cultivation of energy plants by combining LCA with ecosystem/biogeochemical
      process models. LCA presents a general framework for evaluating the energy
      consumption and GHG emission from energy crop planting, yield acquisition,
      production, product use, and postprocessing. Meanwhile, ecosystem/biogeochemical
      process models are adopted to simulate the fluxes and storage of energy, water,
      carbon, and nitrogen in the soil-plant (energy crops) soil continuum. Although
      clear progress has been made in recent years, some problems still exist in
      current studies and should be addressed. This paper reviews the state-of-the-art
      method for estimating GHG emission reduction through developing energy crops and
      introduces in detail a new approach for assessing GHG emission reduction by
      combining LCA with biogeochemical process models. The main achievements of this
      study along with the problems in current studies are described and discussed. 

PMID- 25045737
TI  - Intuitionistic linguistic weighted Bonferroni mean operator and its application
      to multiple attribute decision making.
AB  - The intuitionistic linguistic variables are easier to describe the fuzzy
      information which widely exists in the real world, and Bonferroni mean can
      capture the interrelationship of the individual arguments. However, the
      traditional Bonferroni mean can only process the crisp number. In this paper, we
      will extend Bonferroni mean to the intuitionistic linguistic environment and
      propose a multiple attribute decision making method with intuitionistic
      linguistic information based on the extended Bonferroni mean which can consider
      the interrelationship of the attributes. Firstly, score function and accuracy
      function of intuitionistic linguistic numbers are introduced. Then, an
      intuitionistic linguistic Bonferroni mean (ILBM) operator and an intuitionistic
      linguistic weighted Bonferroni mean (ILWBM) operator are developed, and some
      desirable characteristics of them are studied. At the same time, some special
      cases with respect to the parameters p and q in Bonferroni are analyzed. Based on
      the ILWBM operator, the approach to multiple attribute decision making with
      intuitionistic linguistic information is proposed. Finally, an illustrative
      example is given to verify the developed approach and to demonstrate its
      effectiveness. 

PMID- 25045738
TI  - A hybrid sales forecasting scheme by combining independent component analysis
      with K-means clustering and support vector regression.
AB  - Sales forecasting plays an important role in operating a business since it can be
      used to determine the required inventory level to meet consumer demand and avoid
      the problem of under/overstocking. Improving the accuracy of sales forecasting
      has become an important issue of operating a business. This study proposes a
      hybrid sales forecasting scheme by combining independent component analysis (ICA)
      with K-means clustering and support vector regression (SVR). The proposed scheme
      first uses the ICA to extract hidden information from the observed sales data.
      The extracted features are then applied to K-means algorithm for clustering the
      sales data into several disjoined clusters. Finally, the SVR forecasting models
      are applied to each group to generate final forecasting results. Experimental
      results from information technology (IT) product agent sales data reveal that the
      proposed sales forecasting scheme outperforms the three comparison models and
      hence provides an efficient alternative for sales forecasting. 

PMID- 25045739
TI  - On the system of Diophantine equations x2 - 6y2 = -5 and x = az2 - b.
AB  - Mignotte and Petho used the Siegel-Baker method to find all the integral
      solutions (x, y, z) of the system of Diophantine equations x (2) - 6y (2) = -5
      and x = 2z (2) - 1. In this paper, we extend this result and put forward a
      generalized method which can completely solve the family of systems of
      Diophantine equations x (2) - 6y (2) = -5 and x = az (2) - b for each pair of
      integral parameters a, b. The proof utilizes algebraic number theory and p-adic
      analysis which successfully avoid discussing the class number and factoring the
      ideals. 

PMID- 25045741
TI  - Analyzing patients' values by applying cluster analysis and LRFM model in a
      pediatric dental clinic in Taiwan.
AB  - This study combines cluster analysis and LRFM (length, recency, frequency, and
      monetary) model in a pediatric dental clinic in Taiwan to analyze patients'
      values. A two-stage approach by self-organizing maps and K-means method is
      applied to segment 1,462 patients into twelve clusters. The average values of L,
      R, and F excluding monetary covered by national health insurance program are
      computed for each cluster. In addition, customer value matrix is used to analyze
      customer values of twelve clusters in terms of frequency and monetary. Customer
      relationship matrix considering length and recency is also applied to classify
      different types of customers from these twelve clusters. The results show that
      three clusters can be classified into loyal patients with L, R, and F values
      greater than the respective average L, R, and F values, while three clusters can
      be viewed as lost patients without any variable above the average values of L, R,
      and F. When different types of patients are identified, marketing strategies can
      be designed to meet different patients' needs. 

PMID- 25045740
TI  - Micropropagation of bioencapsulation and ultrastructural features of sainfoin
      (Onobrychis viciifolia) grown in vivo and in vitro.
AB  - To explore the potential of in vitro rapid regeneration, three varieties
      (Golpaygan-181, Orumieh-1763, and Gorgan-1601) of sainfoin (Onobrychis viciifolia
      Scop. syn. Onobrychis sativa L.) were evaluated. For the first time, an
      encapsulation protocol was established from somatic embryogenic callus in torpedo
      and cotyledonary stages to create artificial seeds. Callus derived from different
      concentrations of Kinetin (0-2.0 mg L(-1)) and Indole-3-acetic acid (0-2.0 mg L(
      1)) was coated with sodium alginate and subsequently cultured either in Murashige
      and Skoog (MS) medium or in soil substrate. Adventitious shoots from synthetic
      beads developed into rooting in full and half strength MS medium supplemented
      with various concentrations of auxin and cytokinin. Prolonged water conservation
      of black and red soils (1:1) had the highest rate of survival plantlets in the
      acclimatization process. Diverse resistance techniques in Onobrychis viciifolia
      were evaluated when the plants were subjected to water deficiency. Higher
      frequency of epicuticular waxes was observed in in vivo leaves compared to in
      vitro leaves. Jagged trichomes nonsecreting glands covered by spines were only
      observed in the lower leaf side. Ultimately, stomata indices were 0.127
      (abaxial), 0.188 (adaxial) in in vivo and 0.121 (abaxial), 0.201 (adaxial) in in
      vitro leaves.

PMID- 25045742
TI  - Photosynthetic and canopy characteristics of different varieties at the early
      elongation stage and their relationships with the cane yield in sugarcane.
AB  - During sugarcane growth, the Early Elongation stage is critical to cane yield
      formation. In this study, parameters of 17 sugarcane varieties were determined at
      the Early Elongation stage using CI-301 photosynthesis measuring system and CI
      100 digital plant canopy imager. The data analysis showed highly significant
      differences in leaf area index (LAI), mean foliage inclination angle (MFIA),
      transmission coefficient for diffused light penetration (TD), transmission
      coefficient for solar beam radiation penetration (TR), leaf distribution (LD),
      net photosynthetic rate (PN), transpiration rate (E), and stomatal conductance
      (GS) among sugarcane varieties. Based on the photosynthetic or canopy parameters,
      the 17 sugarcane varieties were classified into four categories. Through the
      factor analysis, nine parameters were represented by three principal factors, of
      which the cumulative rate of variance contributions reached 85.77%. A regression
      for sugarcane yield, with relative error of yield fitting less than 0.05, was
      successfully established: sugarcane yield = -27.19 - 1.69 * PN + 0.17 * E + 90.43
      * LAI - 408.81 * LD + 0.0015 * NSH + 101.38 * D (R(2) = 0.928**). This study
      helps provide a theoretical basis and technical guidance for the screening of new
      sugarcane varieties with high net photosynthetic rate and ideal canopy structure.

PMID- 25045743
TI  - Protective effects of trehalose on the corneal epithelial cells.
AB  - PURPOSE: Aim of the present work was to evaluate the effects of the trehalose on
      the corneal epithelium undergoing alcohol delamination. METHODS: Twelve patients
      undergoing laser subepithelial keratomileusis (LASEK) were consecutively included
      in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst
      left eyes were used as control. Epithelial specimens were processed for cells
      vitality assessment, apoptosis, and light and transmission electron microscopy; a
      morphometric analysis was performed in both groups. RESULTS: In both trehalose
      untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital
      cells was similar and no apoptotic cells were observed. In TUE, the corneal
      epithelium showed superficial cells with reduced microfolds, wing cells with
      vesicles and dilated intercellular spaces, and dark basal cells with vesicles and
      wide clefts. In TTE, superficial and wing cells were better preserved, and basal
      cells were generally clear with intracytoplasmatic vesicles. The morphometric
      analysis showed statistically significant differences between the two groups: the
      TTE epithelial height was higher, the basal cells showed larger area and clearer
      cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly
      different between the groups. CONCLUSIONS: Trehalose administration better
      preserved morphological and morphometric features of alcohol-treated corneal
      epithelium, when compared to controls.

PMID- 25045744
TI  - Normalized Difference Vegetation Index as a tool for wheat yield estimation: a
      case study from Faisalabad, Pakistan.
AB  - For estimation of grain yield in wheat, Normalized Difference Vegetation Index
      (NDVI) is considered as a potential screening tool. Field experiments were
      conducted to scrutinize the response of NDVI to yield behavior of different wheat
      cultivars and nitrogen fertilization at agronomic research area, University of
      Agriculture Faisalabad (UAF) during the two years 2008-09 and 2009-10. For
      recording the value of NDVI, Green seeker (Handheld-505) was used. Split plot
      design was used as experimental model in, keeping four nitrogen rates (N1 = 0 kg
      ha(-1), N2 = 55 kg ha(-1), N3 = 110 kg ha(-1), and N4 = 220 kg ha(-1)) in main
      plots and ten wheat cultivars (Bakkhar-2001, Chakwal-50, Chakwal-97, Faisalabad
      2008, GA-2002, Inqlab-91, Lasani-2008, Miraj-2008, Sahar-2006, and Shafaq-2006)
      in subplots with four replications. Impact of nitrogen and difference between
      cultivars were forecasted through NDVI. The results suggested that nitrogen
      treatment N4 (220 kg ha(-1)) and cultivar Faisalabad-2008 gave maximum NDVI value
      (0.85) at grain filling stage among all treatments. The correlation among NDVI at
      booting, grain filling, and maturity stages with grain yield was positive (R(2) =
      0.90; R(2) = 0.90; R(2) = 0.95), respectively. So, booting, grain filling, and
      maturity can be good depictive stages during mid and later growth stages of wheat
      crop under agroclimatic conditions of Faisalabad and under similar other wheat
      growing environments in the country.

PMID- 25045745
TI  - New sufficient conditions for Hamiltonian paths.
AB  - A Hamiltonian path in a graph is a path involving all the vertices of the graph.
      In this paper, we revisit the famous Hamiltonian path problem and present new
      sufficient conditions for the existence of a Hamiltonian path in a graph. 

PMID- 25045746
TI  - On soft beta-open sets and soft beta-continuous functions.
AB  - We introduce the concepts soft beta-interior and soft beta-closure of a soft set
      in soft topological spaces. We also study soft beta-continuous functions and
      discuss their relations with soft continuous and other weaker forms of soft
      continuous functions. 

PMID- 25045747
TI  - A novel deployment scheme based on three-dimensional coverage model for wireless
      sensor networks.
AB  - Coverage pattern and deployment strategy are directly related to the optimum
      allocation of limited resources for wireless sensor networks, such as energy of
      nodes, communication bandwidth, and computing power, and quality improvement is
      largely determined by these for wireless sensor networks. A three-dimensional
      coverage pattern and deployment scheme are proposed in this paper. Firstly, by
      analyzing the regular polyhedron models in three-dimensional scene, a coverage
      pattern based on cuboids is proposed, and then relationship between coverage and
      sensor nodes' radius is deduced; also the minimum number of sensor nodes to
      maintain network area's full coverage is calculated. At last, sensor nodes are
      deployed according to the coverage pattern after the monitor area is subdivided
      into finite 3D grid. Experimental results show that, compared with traditional
      random method, sensor nodes number is reduced effectively while coverage rate of
      monitor area is ensured using our coverage pattern and deterministic deployment
      scheme. 

PMID- 25045748
TI  - Toxicity effects of toad (Rhinella jimi Stevaux, 2002) venom in chicken (Gallus
      gallus domesticus).
AB  - This study aimed to evaluate the pathological changes that occur after
      administering different doses of R. jimi (Stevaux, 2002) parotoid glands
      secretion to Gallus gallus domesticus chicks. Twenty-three animals were used in
      this study and were divided into 5 groups that received a toad venom dose of 0,
      3.0 mg/kg, 6.0 mg/kg, 10.0 mg/kg, and 25.0 mg/kg. After 48 h, the necropsy and
      pathological examinations were performed. No clinical signs of toxicity were
      observed in any group. Macroscopically, hepatomegaly, areas of liver necrosis,
      splenomegaly, necrotic and hemorrhagic cardiac regions, hydropericardium, dark
      necrotic lesions of Meckel's diverticulum, and hemorrhages in the lungs and
      kidneys were detected. Histopathological changes included diffuse vacuolar
      degeneration of hepatocytes, severe sinusoidal congestion, focal areas of
      hemorrhage in the parenchyma, swollen cardiac fibers, necrotic myocardial fibers,
      moderate to acute diffuse alveolar hemorrhage, vacuolar degeneration of the renal
      tubular epithelium, necrosis of renal tubules, and extensive hemorrhagic areas
      below the brain and cerebellar meninges. In conclusion, pathological changes of
      the R. jimi toxins in chicks were noted in the heart, spleen, liver, Meckel's
      diverticulum, lungs, and kidneys. Most of the changes were similar to those
      observed in humans and animals exposed to toxins from other toad species.

PMID- 25045749
TI  - Synthesis and performance evaluation of a new deoiling agent for treatment of
      waste oil-based drilling fluids.
AB  - Oil-based drilling fluid is used more and more in the field of oil and gas
      exploration. However, because of unrecyclable treating agent and hard treatment
      conditions, the traditional treating technologies of waste oil-based drilling
      fluid have some defects, such as waste of resource, bulky equipment, complex
      treatment processes, and low oil recovery rate. In this work, switchable deoiling
      agent (SDA), as a novel surfactant for treatment of waste oil-based drilling
      fluid, was synthesized by amine, formic acid, and formaldehyde solution. With
      this agent, the waste oil-based drilling fluid can be treated without complex
      process and expensive equipment. Furthermore, the agent used in the treatment can
      be recycled, which reduces waste of resource and energy. The switch performance,
      deoiling performance, structural characterization, and mechanisms of action are
      studied. The experimental results show that the oil content of the recycled oil
      is higher than 96% and more than 93% oil in waste oil-based drilling fluid can be
      recycled. The oil content of the solid residues of deoiling is less than 3%. 

PMID- 25045750
TI  - A novel support vector machine with globality-locality preserving.
AB  - Support vector machine (SVM) is regarded as a powerful method for pattern
      classification. However, the solution of the primal optimal model of SVM is
      susceptible for class distribution and may result in a nonrobust solution. In
      order to overcome this shortcoming, an improved model, support vector machine
      with globality-locality preserving (GLPSVM), is proposed. It introduces globality
      locality preserving into the standard SVM, which can preserve the manifold
      structure of the data space. We complete rich experiments on the UCI machine
      learning data sets. The results validate the effectiveness of the proposed model,
      especially on the Wine and Iris databases; the recognition rate is above 97% and
      outperforms all the algorithms that were developed from SVM. 

PMID- 25045751
TI  - Spatial and temporal variation in fine particulate matter mass and chemical
      composition: the Middle East Consortium for Aerosol Research Study.
AB  - Ambient fine particulate matter (PM2.5) samples were collected from January to
      December 2007 to investigate the sources and chemical speciation in Palestine,
      Jordan, and Israel. The 24-h PM2.5 samples were collected on 6-day intervals at
      eleven urban and rural sites simultaneously. Major chemical components including
      metals, ions, and organic and elemental carbon were analyzed. The mass
      concentrations of PM2.5 across the 11 sites varied from 20.6 to 40.3 MUg/m(3),
      with an average of 28.7 MUg/m(3). Seasonal variation of PM2.5 concentrations was
      substantial, with higher average concentrations (37.3 MUg/m(3)) in the summer
      (April-June) months compared to winter (October-December) months (26.0 MUg/m(3))
      due mainly to high contributions of sulfate and crustal components. PM2.5
      concentrations in the spring were greatly impacted by regional dust storms.
      Carbonaceous mass was the most abundant component, contributing 40% to the total
      PM2.5 mass averaged across the eleven sites. Crustal components averaged 19.1% of
      the PM2.5 mass and sulfate, ammonium, and nitrate accounted for 16.2%, 6.4%, and
      3.7%, respectively, of the total PM2.5 mass. The results of this study
      demonstrate the need to better protect the health and welfare of the residents on
      both sides of the Jordan River in the Middle East.

PMID- 25045752
TI  - Novel applications of intuitionistic fuzzy digraphs in decision support systems.
AB  - Many problems of practical interest can be modeled and solved by using graph
      algorithms. In general, graph theory has a wide range of applications in diverse
      fields. In this paper, the intuitionistic fuzzy organizational and neural network
      models, intuitionistic fuzzy neurons in medical diagnosis, intuitionistic fuzzy
      digraphs in vulnerability assessment of gas pipeline networks, and intuitionistic
      fuzzy digraphs in travel time are presented as examples of intuitionistic fuzzy
      digraphs in decision support system. We have also designed and implemented the
      algorithms for these decision support systems. 

PMID- 25045753
TI  - Effect of noni (Morinda citrifolia Linn.) fruit and its bioactive principles
      scopoletin and rutin on rat vas deferens contractility: an ex vivo study.
AB  - This study examined the effect of methanolic extract of Morinda citrifolia Linn.
      (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and
      noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC
      (1-40 mg/mL), scopoletin (1-200 MUg/mL), and rutin hydrate (0.6-312.6 MUg/mL)
      dose-dependently inhibited the contractility evoked by submaximal concentrations
      of both dopamine and noradrenaline, respectively. Haloperidol and prazosin,
      reference dopamine D2, and alpha 1-adrenoceptors antagonists significantly
      reversed the dopamine- and noradrenaline-induced contractions, respectively, in a
      dose-dependent manner. Interestingly, MMC per se at higher doses (60-100 mg/mL)
      showed dose-dependent contractile response in rat vas deferens which was
      partially inhibited by high doses of haloperidol but not by prazosin. These
      results demonstrated the biphasic effects of MMC on dopaminergic system; that is,
      antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic
      agonistic effect at higher concentrations (>60 mg/mL). However, similar
      contractile response at high doses of scopoletin (0.5-5 mg/mL) and rutin hydrate
      (0.5-5 mg/mL) per se was not observed. Therefore, it can be concluded that the
      bioactive principles of MMC, scopoletin, and rutin might be responsible for the
      antidopaminergic and antiadrenergic activities of MMC.

PMID- 25045754
TI  - Singularity-free neural control for the exponential trajectory tracking in
      multiple-input uncertain systems with unknown deadzone nonlinearities.
AB  - The trajectory tracking for a class of uncertain nonlinear systems in which the
      number of possible states is equal to the number of inputs and each input is
      preceded by an unknown symmetric deadzone is considered. The unknown dynamics is
      identified by means of a continuous time recurrent neural network in which the
      control singularity is conveniently avoided by guaranteeing the invertibility of
      the coupling matrix. Given this neural network-based mathematical model of the
      uncertain system, a singularity-free feedback linearization control law is
      developed in order to compel the system state to follow a reference trajectory.
      By means of Lyapunov-like analysis, the exponential convergence of the tracking
      error to a bounded zone can be proven. Likewise, the boundedness of all closed
      loop signals can be guaranteed. 

PMID- 25045755
TI  - 2.4 GHz CMOS power amplifier with mode-locking structure to enhance gain.
AB  - We propose a mode-locking method optimized for the cascode structure of an RF
      CMOS power amplifier. To maximize the advantage of the typical mode-locking
      method in the cascode structure, the input of the cross-coupled transistor is
      modified from that of a typical mode-locking structure. To prove the feasibility
      of the proposed structure, we designed a 2.4 GHz CMOS power amplifier with a 0.18
      MUm RFCMOS process for polar transmitter applications. The measured power added
      efficiency is 34.9%, while the saturated output power is 23.32 dBm. The designed
      chip size is 1.4 * 0.6 mm(2).

PMID- 25045756
TI  - Conservative Sample Size Determination for Repeated Measures Analysis of
      Covariance.
AB  - In the design of a randomized clinical trial with one pre and multiple post
      randomized assessments of the outcome variable, one needs to account for the
      repeated measures in determining the appropriate sample size. Unfortunately, one
      seldom has a good estimate of the variance of the outcome measure, let alone the
      correlations among the measurements over time. We show how sample sizes can be
      calculated by making conservative assumptions regarding the correlations for a
      variety of covariance structures. The most conservative choice for the
      correlation depends on the covariance structure and the number of repeated
      measures. In the absence of good estimates of the correlations, the sample size
      is often based on a two-sample t-test, making the 'ultra' conservative and
      unrealistic assumption that there are zero correlations between the baseline and
      follow-up measures while at the same time assuming there are perfect correlations
      between the follow-up measures. Compared to the case of taking a single
      measurement, substantial savings in sample size can be realized by accounting for
      the repeated measures, even with very conservative assumptions regarding the
      parameters of the assumed correlation matrix. Assuming compound symmetry, the
      sample size from the two-sample t-test calculation can be reduced at least 44%,
      56%, and 61% for repeated measures analysis of covariance by taking 2, 3, and 4
      follow-up measures, respectively. The results offer a rational basis for
      determining a fairly conservative, yet efficient, sample size for clinical trials
      with repeated measures and a baseline value.

PMID- 25045758
TI  - A three-dimensional interpenetrating electrode of reduced graphene oxide for
      selective detection of dopamine.
AB  - Electrochemical detection of dopamine plays an important role in medical
      diagnosis. In this paper, we report a three-dimensional (3D) interpenetrating
      graphene electrode fabricated by electrochemical reduction of graphene oxide for
      selective detection of dopamine. This electrochemically reduced graphene oxide
      (ErGO) electrode was used directly without further functionalization or blending
      with other functional materials. This electrode can efficiently lower the
      oxidation potential of ascorbic acid; thus, it is able to selectively detect
      dopamine in the presence of ascorbic acid and uric acid. The ErGO-based biosensor
      exhibited a linear response towards dopamine in the concentration range of 0.1-10
      MUM with a low detection limit of 0.1 MUM. Furthermore, this electrode has good
      reproducibility and environmental stability, and can be used to analyse real
      samples. 

PMID- 25045759
TI  - Fabrication of a microfluidic paper-based analytical device by silanization of
      filter cellulose using a paper mask for glucose assay.
AB  - We developed a novel, low-cost and simple method for the fabrication of
      microfluidic paper-based analytical devices (MUPADs) by silanization of filter
      cellulose using a paper mask having a specific pattern. The paper mask was
      penetrated with trimethoxyoctadecylsilane (TMOS) by immersing into TMOS-heptane
      solution. By heating the filter paper sandwiched between the paper mask and glass
      slides, TMOS was immobilized onto the filter cellulose via the reaction between
      cellulose OH and TMOS, while the hydrophilic area was not silanized because it
      was not in contact with the paper mask penetrated with TMOS. The effects of some
      factors including TMOS concentration, heating temperature and time on the
      fabrication of MUPADs were studied. This method is free of any expensive
      equipment and metal masks, and could be performed by untrained personnel. These
      features are very attractive for the fabrication and applications of MUPADs in
      developing countries or resource-limited settings. A flower-shaped MUPAD was
      fabricated and used to determine glucose in human serum samples. The contents
      determined by this method agreed well with those determined by a standard method.

PMID- 25045761
TI  - Thin films of spin-crossover coordination polymers with large thermal hysteresis
      loops prepared by nanoparticle spin coating.
AB  - This communication describes the synthesis of spin-crossover nanoparticles, which
      can disperse in various organic solvents without an excess amount of surfactants.
      The nanoparticles form homogeneous thin films on substrates by spin coating. The
      films show abrupt spin transitions with large thermal hysteresis loops. 

PMID- 25045760
TI  - The extraordinary catalytic ability of peroxiredoxins: a combined experimental
      and QM/MM study on the fast thiol oxidation step.
AB  - Peroxiredoxins (Prxs) catalyze the reduction of peroxides, a process of key
      relevance in a variety of cellular processes. The first step in the catalytic
      cycle of all Prxs is the oxidation of a cysteine residue to sulfenic acid, which
      occurs 10(3)-10(7) times faster than in free cysteine. We present an experimental
      kinetics and hybrid QM/MM investigation to explore the reaction of Prxs with H2O2
      using alkyl hydroperoxide reductase E from Mycobacterium tuberculosis as a Prx
      model. We report for the first time the thermodynamic activation parameters of
      H2O2 reduction using Prx, which show that protein significantly lowers the
      activation enthalpy, with an unfavourable entropic effect, compared to the
      uncatalyzed reaction. The QM/MM simulations show that the remarkable catalytic
      effects responsible for the fast H2O2 reduction in Prxs are mainly due to an
      active-site arrangement, which establishes a complex hydrogen bond network
      activating both reactive species. 

PMID- 25045762
TI  - Self-assembly of long chain fatty acids: effect of a methyl branch.
AB  - The morphology and molecular conformation of Langmuir-Blodgett deposited and
      floating monolayers of a selection of straight chain (eicosanoic acid, EA), iso
      (19-methyl eicosanoic acid, 19-MEA), and anteiso (18-methyl eicosanoic acid, 18
      MEA) fatty acids have been investigated by Vibrational Sum Frequency Spectroscopy
      (VSFS), AFM imaging, and the Langmuir trough. While the straight chain fatty acid
      forms smooth, featureless monolayers, all the branched chain fatty acids display
      10-50 nm sized domains (larger for 19-MEA than the 18-MEA) with a homogeneous
      size distribution. A model is suggested to explain the domain formation and size
      in terms of the branched fatty acid packing properties and the formation of
      hemispherical caps at the liquid-air interface. No difference between the chiral
      (S) form and the racemic mixture of the 18-MEA is observed with any of the
      utilized techniques. The aliphatic chains of the straight chain fatty acids
      appear to be oriented perpendicular to the sample surface, based on an
      orientational analysis of VSFS data and the odd/even effect. In addition, the
      selection of the subphase (neat water or CdCl2 containing water buffered to pH
      6.0) used for the LB-deposition has a profound influence on the monolayer
      morphology, packing density, compressibility, and conformational order. Finally,
      the orientation of the 19-MEA dimethyl moiety is estimated, and a strategy for
      performing an orientational analysis to determine the complete molecular
      orientation of the aliphatic chains of 19-MEA and 18-MEA is outlined and
      discussed. 

PMID- 25045763
TI  - Stochastic surface walking method for crystal structure and phase transition
      pathway prediction.
AB  - The determination of crystal structures and the solid-to-solid phase transition
      mechanisms are two important and related subjects in material science. Here we
      develop an unbiased general-purpose potential energy surface (PES) searching
      method, namely, SSW-crystal method, for prediction of both the crystal structure
      and the crystal phase transition pathway. The SSW-crystal method features with
      stochastic surface walking (SSW) via repeated small structural perturbation by
      taking into account the second derivative information on both the lattice and the
      atom degrees of freedom. The SSW-crystal method is capable of overcoming the high
      barrier of phase transition and identifying the desirable phase transition
      reaction coordinates. By applying the SSW-crystal method to a set of examples,
      including SiO2 crystal up to 162 atoms per cell, Lennard-Jones model crystals up
      to 256 atoms, ternary SrTiO3 crystal of 50 atoms and the rutile-to-anatase TiO2
      phase transition, we show that the SSW-crystal method can efficiently locate the
      global minimum (GM) from random initial structures without a priori knowledge of
      the system, and also allows for exhaustive sampling of the phase transition
      pathways, from which the lowest energy pathway can be obtained. 

PMID- 25045764
TI  - Drastic change of the intrusion-extrusion behavior of electrolyte solutions in
      pure silica *BEA-type zeolite.
AB  - High pressure water and electrolyte solutions intrusion-extrusion experiments in
      pure-silica *BEA-type zeolite (zeosil beta) were performed in order to study the
      performances of these systems in energy absorption and storage. The "zeosil beta
      water" system displays a bumper behavior with an intrusion pressure of 53 MPa and
      an absorbed energy of 8.3 J g(-1). For the "zeosil beta-LiCl aqueous solutions"
      systems the intrusion pressure increases with the LiCl concentration to 95, 111
      and 115 MPa for 10, 15 and 20 M solution, respectively. However, for
      concentrations above 10 M, a transformation of the system behavior from bumper to
      shock-absorber is observed. The zeolite samples were characterized by several
      structural and physicochemical methods (XRD, TGA, solid-state NMR, N2
      physisorption, ICP-OES) before and after intrusion-extrusion experiments in order
      to understand the influence of the LiCl concentration on the intrusion-extrusion
      behavior. It is shown that the intrusion of water and LiCl solutions with low
      concentration leads to the formation of Si-(OSi)3OH groups, whereas no defects
      are observed under intrusion of concentrated LiCl solutions. A possible mechanism
      of LiCl solution intrusion based on separate intrusion of H2O molecules and
      Li(H2O)x(+) ions is proposed. 

PMID- 25045765
TI  - From semiconductor nanocrystals to artificial solids with dimensionality below
      two.
AB  - Two-dimensional films of semiconductors can be patterned into super-lattices with
      nanoscale periodicity, using top-down (lithography) or bottom-up approaches. In
      particular, square and honeycomb lattices of semiconductor nanocrystals have been
      recently synthesized using oriented attachment. We have performed atomistic tight
      binding calculations of the conduction bands of super-lattices of CdSe. We
      consider spherical nanocrystals connected by horizontal cylinders and we
      investigate the band structure between two extreme limits, the uniform two
      dimensional film, and the assembly of disconnected nanocrystals. Using this model
      system, we explain how rich band structures emerge from the periodic nano
      geometry, including Dirac cones and non-trivial flat bands in honeycomb lattices.
      The possibility to build non-conventional band structures using multi-orbital
      artificial atoms (nanocrystals) opens up new prospects. 

PMID- 25045766
TI  - Experimental and simulation studies of unusual current blockade induced by
      translocation of small oxidized PEG through a single nanopore.
AB  - Detection of a single macromolecule based on the use of artificial nanopores is
      an attractive and promising field of research. In this work, we report a device
      based on a 5 nm single nanopore with a high length/diameter ratio, tailored by
      the track etching and atomic layer deposition techniques. The translocation of
      neutral polyethylene glycol (PEG) and charged polyethylene glycol-carboxylate
      (PEG-carboxylate) molecules of low molar masses (200 and 600 g mol(-1)) through
      this nanodevice was studied. It was shown that charged PEG-carboxylate molecules,
      which permeate through the pore, promote an unusual blockade of ionic current
      whereas the neutral PEG molecules do not show such behaviour. The molecular
      dynamics simulation shows that both neutral and charged PEGs permeate through the
      nanopore close to its inner surface. The main difference between the two
      macromolecules is the existence of a structured shell of cations around the
      charged PEG, which is likely to cause the observed unusual current blockade. 

PMID- 25045767
TI  - Examination of surface phenomena of V2O5 loaded on new nanostructured TiO2
      prepared by chemical vapor condensation for enhanced NH3-based selective
      catalytic reduction (SCR) at low temperatures.
AB  - In this article, we describe the investigation and surface characterization of a
      chemical vapor condensation (CVC)-TiO2 support material used in a V2O5/TiO2
      catalyst for enhanced selective catalytic reduction (SCR) activity and confirm
      the mechanism of surface reactions. On the basis of previous studies and
      comparison with a commercial TiO2 catalyst, we examine four fundamental
      questions: first, the reason for increased surface V(4+) ion concentrations;
      second, the origin of the increase in surface acid sites; third, a basis for
      synergistic influences on improvements in SCR activity; and fourth, a reason for
      improved catalytic activity at low reaction temperatures. In this study, we have
      cited the result of SCR with NH3 activity for removing NOx and analyzed data
      using the reported result and data from previous studies on V2O5/CVC-TiO2 for the
      SCR catalyst. In order to determine the properties of suitable CVC-TiO2 surfaces
      for efficient SCR catalysis at low temperatures, CVC-TiO2 specimens were prepared
      and characterized using techniques such as XRD, BET, HR-TEM, XPS, FT-IR, NH3-TPD,
      photoluminescence (PL) spectroscopy, H2-TPR, and cyclic voltammetry. The results
      obtained for the CVC-TiO2 materials were also compared with those of commercial
      TiO2. 

PMID- 25045768
TI  - Distribution of fluoride and calcium in plaque biofilms after  the use of
      conventional and low-fluoride dentifrices.
AB  - BACKGROUND: The distribution of fluoride and calcium in plaque after the use of
      fluoride dentifrices has not yet been determined. AIM: To evaluate fluoride and
      calcium distribution in sections of biofilms generated in situ after the use of
      conventional and low-fluoride dentifrices. DESIGN: Children (n = 11, 8-10 years
      old) brushed with placebo (fluoride-free), low-fluoride (513 mgF/kg), and
      conventional (1072 mgF/kg) dentifrices twice daily for 1 week, following a double
      blind, cross-over protocol. Biofilms were generated using Leeds in situ devices,
      which were collected 1 and 12 h after brushing, and sectioned through their
      depth. Sections were grouped (10 x 5 MUm) for fluoride and calcium analysis.
      Sections 4 lm thick were used for image analysis and determination of biomass
      fraction. Results were analysed by ANOVA, Tukey's test, and linear regression
      analysis (P < 0.05). RESULTS: Fluoride and calcium were mostly located at the
      outer sections of biofilms for all dentifrices tested, and these ions were
      directly correlated throughout most of biofilm's sections. Results for
      conventional dentifrice were significantly higher than for the placebo, but did
      not differ from those for the low-fluoride dentifrice. CONCLUSIONS: The use of a
      low-fluoride dentifrice did not promote a higher fluoride uptake in inner
      biofilms' sections, as hypothesized. As plaque fluoride was significantly
      elevated only after the use of the conventional dentifrice, the recommendation of
      low-fluoride formulations should be done with caution, considering both risks and
      benefits.

PMID- 25045769
TI  - Dr. Linda Brodsky.

PMID- 25045770
TI  - To give or not to give antibiotics in non-severe acute otitis media?  The  
      American Academy of Pediatrics guidelines that do not guide.
AB  - OBJECTIVE: To assess whether the recently published guidelines of the American
      Academy of Pediatrics (AAP) on acute otitis media (AOM) are in line with the
      requirements set by the GRADE system (grading of recommendations assessment,
      development, and evaluation system of rating quality of evidence and grading
      strength of recommendations in systematic reviews, health technology assessments,
      and clinical practice guidelines) and to compare them with the most recently
      published related guidelines (Korean and Japanese). RESULTS: The AAP guidelines
      fail to answer the simple and explicit fundamental question on pediatric AOM
      management: whether antibiotics should be prescribed or not in non-severe AOM.
      Instead of giving a type C recommendation (option) if the available evidence was
      considered as inadequate or even a type D (no recommendation) the AAP guideline
      is to prescribe antibiotics or offer a watchful waiting for 48-72 h (strength of
      recommendation type B). This is in sharp contrast with the most recent guidelines
      (Korean and Japanese) that both recommend watchful waiting for 48-72 h (with the
      highest strength of recommendation - type A). CONCLUSION: The AAP guidelines do
      not seem to be in line with the GRADE system as in an important, simple, and
      explicit question on: antibiotic administration in non- severe AOM, given in an
      ambiguous statement. This statement is in reality a vicious circle as the
      guidelines avoid to take any side and do not even categorize the answer as an
      option.

PMID- 25045771
TI  - ACTS: a gathering place for scientists across the full translational science
      spectrums.

PMID- 25045772
TI  - WHO procedures for certification of malaria elimination.

PMID- 25045773
TI  - Global Advisory Committee on Vaccine Safety, 11-12 June 2014.

PMID- 25045774
TI  - Letter to the editor.

PMID- 25045775
TI  - Reply: To PMID 23649321.

PMID- 25045776
TI  - Julian Hart Lewis, F.R.S. (1946-2014).

PMID- 25045777
TI  - Lewis acid promoted diastereoselective addition of TMSCN and TMSCF3 to isatin
      derived N-sulfinyl ketimines: synthesis of optically active tetrasubstituted 3
      aminooxindoles.
AB  - A practical and efficient method for preparation of highly enantiomerically
      enriched 3-cyano-3-aminooxindoles and 3-trifluoromethyl-3-aminooxindoles with up
      to 99% optical purity by a Lewis acid promoted diastereoselective Strecker
      reaction and trifluoromethylation of isatin-derived N-tert-butanesulfinyl
      ketimines has been developed. This protocol allows direct use of N-free isatin
      substrates under mild conditions. 

PMID- 25045778
TI  - Desire for orthodontic treatment and associated factors among adolescents in
      Southern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of the desire for orthodontic treatment and
      investigate associated factors among adolescents in southern Brazil. MATERIALS
      AND METHODS: A cross-sectional study was carried out with 704 adolescents aged 12
      and 13 years at municipal public schools in the city of Balneario Camboriu
      (southern Brazil). The adolescents answered a previously tested questionnaire
      addressing satisfaction with their dental appearance, speech function, chewing
      function, and the desire for orthodontic treatment. The parents/guardians
      answered a questionnaire addressing satisfaction with their child's dental
      appearance and socioeconomic variables. A trained and calibrated orthodontist
      collected clinical data on malocclusion using the Dental Aesthetic Index (DAI).
      Statistical analysis was performed using multivariate Poisson regression with
      robust variance. RESULTS: The prevalence of the desire for orthodontic treatment
      was 69.6% (490/704). In the adjusted analysis, the outcome was significantly more
      prevalent among girls (P < .001), those with difficulty chewing (P  =  .026),
      those dissatisfied with their dental appearance (P < .001), and those with
      greater malocclusion severity (P < .001). The following orthodontic
      characteristics were associated with the desire for orthodontic treatment in the
      multivariate model: diastema in anterior segment (P < .001), anterior maxillary
      irregularity (P < .001), maxillary overjet >=6 mm (P < .001), and mandibular
      overjet (P  =  .047). CONCLUSIONS: The desire for orthodontic treatment among 12-
      and 13-year-old adolescents is influenced by gender, dissatisfaction with one's
      dental appearance, difficulty chewing, malocclusion severity, and orthodontic
      characteristics. These findings should be considered together with normative
      indications regarding the need for orthodontic treatment in adolescents.

PMID- 25045779
TI  - A systematic review of randomized controlled trials of interventions to improve
      adherence among orthodontic patients aged 12 to 18.
AB  - OBJECTIVE: To investigate the effectiveness of interventions to enhance adherence
      among orthodontic patients aged 12 to 18 years. Specific adherence outcomes
      included were recall of information given by the orthodontic team, attendance at
      orthodontic appointments, self-reported oral hygiene behavior, and clinical
      indexes of oral hygiene. MATERIALS AND METHODS: Electronic searches of Medline
      via OVID (January 1, 1966 through March 1, 2012), EMBASE, and the Cochrane
      central register of control trials from its inception through March 2012, as well
      as a hand search, were undertaken to identify relevant studies. RESULTS: Through
      the electronic searches, 381 article were identified. Initial screening of the
      abstracts and titles by all review authors identified 21 articles that met the
      inclusion criteria for this review. The full articles were then retrieved. Four
      randomized controlled trials were found, all of which used different methods of
      intervention: a system of rewards or awards, the Hawthorne effect, written
      information, and demonstration of the microbiology of plaque. All the
      interventions, except the use of award/reward, were associated with improvements
      in adherence. CONCLUSION: The literature advocates the use of several methods to
      improve compliance/adherence among orthodontic patients. Although there is
      insufficient evidence to allow clinicians to choose a single method, the results
      demonstrate the value of spending time with patients to illustrate the importance
      of adherence. Future studies should develop multiple methods of assessing patient
      adherence, including self-report, behavioral observation and recording, and
      change in clinical indexes. Such studies should test different types of
      interventions for effectiveness.

PMID- 25045780
TI  - Programming controlled adhesion of E. coli to target surfaces, cells, and tumors
      with synthetic adhesins.
AB  - In this work we report synthetic adhesins (SAs) enabling the rational design of
      the adhesion properties of E. coli. SAs have a modular structure comprising a
      stable beta-domain for outer membrane anchoring and surface-exposed
      immunoglobulin domains with high affinity and specificity that can be selected
      from large repertoires. SAs are constitutively and stably expressed in an E. coli
      strain lacking a conserved set of natural adhesins, directing a robust, fast, and
      specific adhesion of bacteria to target antigenic surfaces and cells. We
      demonstrate the functionality of SAs in vivo, showing that, compared to wild type
      E. coli, lower doses of engineered E. coli are sufficient to colonize solid
      tumors expressing an antigen recognized by the SA. In addition, lower levels of
      engineered bacteria were found in non-target tissues. Therefore, SAs provide
      stable and specific adhesion capabilities to E. coli against target surfaces of
      interest for diverse applications using live bacteria.

PMID- 25045781
TI  - Comparison of magnetic resonance imaging and ultrasound (MRI-US) fusion-guided
      prostate biopsies obtained from axial and sagittal approaches.
AB  - OBJECTIVE: To compare cancer detection rates and concordance between magnetic
      resonance imaging and ultrasound (MRI-US) fusion-guided prostate biopsy cores
      obtained from axial and sagittal approaches. PATIENTS AND METHODS: Institutional
      records of MRI-US fusion-guided biopsy were reviewed. Detection rates for all
      cancers, Gleason >=3 + 4 cancers, and Gleason >=4 + 3 cancers were computed.
      Agreement between axial and sagittal cores for cancer detection, and frequency
      where one was upgraded the other was computed on a per-target and per-patient
      basis. RESULTS: In all, 893 encounters from 791 patients that underwent MRI-US
      fusion-guided biopsy in 2007-2013 were reviewed, yielding 4688 biopsy cores from
      2344 targets for analysis. The mean age and PSA level at each encounter was 61.8
      years and 9.7 ng/mL (median 6.45 ng/mL). Detection rates for all cancers, >=3 + 4
      cancers, and >=4 + 3 cancers were 25.9%, 17.2%, and 8.1% for axial cores, and
      26.1%, 17.6%, and 8.6% for sagittal cores. Per-target agreement was 88.6%, 93.0%,
      and 96.5%, respectively. On a per-target basis, the rates at which one core
      upgraded or detected a cancer missed on the other were 8.3% and 8.6% for axial
      and sagittal cores, respectively. Even with the inclusion of systematic biopsies,
      omission of axial or sagittal cores would have resulted in missed detection or
      under-characterisation of cancer in 4.7% or 5.2% of patients, respectively.
      CONCLUSION: Cancer detection rates, Gleason scores, and core involvement from
      axial and sagittal cores are similar, but significant cancer may be missed if
      only one core is obtained for each target. Discordance between axial and sagittal
      cores is greatest in intermediate-risk scenarios, where obtaining multiple cores
      may improve tissue characterisation.

PMID- 25045783
TI  - Legislative Action to Promote Breastfeeding.

PMID- 25045782
TI  - Stimuli-responsive hydrogels in drug delivery and tissue engineering.
AB  - Hydrogels are the three-dimensional network structures obtained from a class of
      synthetic or natural polymers which can absorb and retain a significant amount of
      water. Hydrogels are one of the most studied classes of polymer-based controlled
      drug release. These have attracted considerable attention in biochemical and
      biomedical fields because of their characteristics, such as swelling in aqueous
      medium, biocompatibility, pH and temperature sensitivity or sensitivity towards
      other stimuli, which can be utilized for their controlled zero-order release. The
      hydrogels are expected to explore new generation of self-regulated delivery
      system having a wide array of desirable properties. This review highlights the
      exciting opportunities and challenges in the area of hydrogels. Here, we review
      different literatures on stimuli-sensitive hydrogels, such as role of
      temperature, electric potential, pH and ionic strength to control the release of
      drug from hydrogels. 

PMID- 25045785
TI  - Mapping the protein interaction landscape for fully functionalized small-molecule
      probes in human cells.
AB  - Phenotypic screening provides a means to discover small molecules that perturb
      cell biological processes. Discerning the proteins and biochemical pathways
      targeted by screening hits, however, remains technically challenging. We recently
      described the use of small molecules bearing photoreactive groups and latent
      affinity handles as fully functionalized probes for integrated phenotypic
      screening and target identification. The general utility of such probes, or, for
      that matter, any small-molecule screening library, depends on the scope of their
      protein interactions in cells, a parameter that remains largely unexplored. Here,
      we describe the synthesis of an ~60-member fully functionalized probe library,
      prepared from Ugi-azide condensation reactions to impart structural diversity and
      introduce diazirine and alkyne functionalities for target capture and enrichment,
      respectively. In-depth mass spectrometry-based analysis revealed a diverse array
      of probe targets in human cells, including enzymes, channels, adaptor and
      scaffolding proteins, and proteins of uncharacterized function. For many of these
      proteins, ligands have not yet been described. Most of the probe-protein
      interactions showed well-defined structure-activity relationships across the
      probe library and were blocked by small-molecule competitors in cells. These
      findings indicate that fully functionalized small molecules canvas diverse
      segments of the human proteome and hold promise as pharmacological probes of cell
      biology.

PMID- 25045786
TI  - Iridium oxide-polymer nanocomposite electrode materials for water oxidation.
AB  - Nanocomposite anode materials for water oxidation have been readily synthesized
      by electrodeposition of iridium oxide nanoparticles into poly(pyrrole
      alkylammonium) films, previously deposited onto carbon electrodes by oxidative
      electropolymerization of a pyrrole-alkylammonium monomer. The nanocomposite films
      were characterized by electrochemistry, transmission electron microscopy, and
      atomic force microscopy. They showed an efficient electrocatalytic activity
      toward the oxygen evolution reaction. Data from Tafel plots have demonstrated
      that the catalytic activity of the iridium oxide nanoparticles is maintained
      following their inclusion in the polymer matrix. Bulk electrolysis of water at
      carbon foam modified electrodes have shown that the iridium oxide-polymer
      composite presents a higher catalytic activity and a better operational stability
      than regular oxide films. 

PMID- 25045784
TI  - Synergistic inhibitory effect of berberine and d-limonene on human gastric
      carcinoma cell line MGC803.
AB  - This study aims at evaluating the anticancer effects of berberine hydrochloride
      (berberine) and d-limonene, alone and in combination, on human gastric carcinoma
      cell line MGC803 to determine whether berberine and d-limonene work
      synergistically and elucidate their mechanisms. MGC803 cells were treated with
      berberine and d-limonene, alone and in combination, for 24-48 h. The inhibitory
      effects of these drugs on growth were determined by MTT assay. The combination
      index and drug reduction index were calculated with the Chou-Talalay method based
      on the median-effect principle. Flow cytometry and laser scanning confocal
      microscopy were employed to evaluate the effects of both drugs on cell-cycle
      perturbation and apoptosis, generation of reactive oxygen species (ROS),
      mitochondrial membrane potential, and expression of Bcl-2 and caspase-3 in MGC803
      cells. Berberine or d-limonene alone can inhibit the growth of MGC803 cells in a
      dose- and time-dependent manner. Berberine and d-limonene at a combination ratio
      of 1:4 exhibited a synergistic effect on anti-MGC803 cells. The two drugs
      distinctly induced intracellular ROS generation, reduced the mitochondrial
      transmembrane potential (DeltaPsim), enhanced the expression of caspase-3, and
      decreased the expression of Bcl-2. The combination of berberine and d-limonene
      showed more remarkable effects compared with drugs used singly in MGC803 cells.
      The combination of berberine and d-limonene exerted synergistic anticancer
      effects on MGC803 cells by cell-cycle arrest, ROS production, and apoptosis
      induction through the mitochondria-mediated intrinsic pathway.

PMID- 25045787
TI  - Nationwide survey of decompressive hemicraniectomy for malignant middle cerebral
      artery infarction in Japan.
AB  - OBJECTIVE: Decompressive hemicraniectomy (DHC) for malignant middle cerebral
      artery (MCA) infarction has been shown to reduce mortality and improve functional
      outcomes in young adults; however, there is currently debate regarding how
      routinely such surgery should be performed in the clinical setting, considering
      the very high rate of disability and functional dependence among survivors. We
      herein report the current status of the frequency of and indications for DHC for
      malignant MCA infarction in Japan. METHODS: We retrospectively studied of cohort
      cases of DHC for malignant MCA infarction treated at pivotal teaching
      neurosurgical departments in Japan between January 2011 and December 2011.
      Information was obtained regarding patient characteristics, radiologic features,
      and outcomes during follow-up. The end points included 30-day mortality rate and
      functional outcomes, as measured according to the modified Rankin scale (mRS)
      score at 3 months. RESULTS: Three hundred fifty-five patients underwent DHC at
      259 neurosurgical departments who replied to the survey, corresponding to a rate
      of 8.7% of the 4092 candidates with malignant MCA infarction, the latter being
      equivalent to 8.5% of patients with acute ischemic stroke identified during the
      same period. Among the patients undergoing DHC, the mean age was 67.0 years, and
      those >=60 years of age comprised 80.2% of all DHC patients. The most frequently
      used modality for vascular imaging was magnetic resonance angiography (77.2%).
      DHC generally was performed between 24 and 48 hours after onset (38.9%), with
      36.9% of patients undergoing surgery at >=48 hours. At the time of surgery, 26.1%
      of the patients had a Glasgow Coma Scale score of <=6. Presurgical midbrain
      compression was noted in 52.1% of the patients. The 30-day mortality after DHC
      was 18.6%, and factors affecting death were a Glasgow Coma Scale score of <=6
      (odds ratio [OR] 1.88, 95% confidence interval [95% CI] 1.05-3.32, P = 0.03) and
      midbrain compression (OR 2.28, 95% CI 1.31-4.09, P = 0.005). According to the
      multivariate analysis, only midbrain compression was an independent risk factor
      (OR 2.12, 95% CI 1.16-3.95, P = 0.01) for 30-day mortality. Modified Rankin scale
      scores at 3 months were available in 175 patients (49.3%), only 5.2% of whom
      exhibited a favorable functional outcome (mRS score <=3). Meanwhile, 22.9% of the
      patients had an mRS score of 4, 26.9% had an mRS score of 5, and 45.1% were found
      to have died. CONCLUSIONS: In the present study, less than one-tenth of
      candidates with malignant MCA infarction in Japan underwent decompressive
      surgery, and the vast majority of patients were elderly. Age was not found to be
      an independent factor for immediate mortality in this study, and performing
      surgery in the elderly may be justified based on additional evidence of
      functional improvements.

PMID- 25045788
TI  - Clinical outcomes and patterns of failure in pineoblastoma: a 30-year, single
      institution retrospective review.
AB  - OBJECTIVE: To update outcomes and assess prognostic factors in the modern,
      multimodality treatment of patients with pineoblastoma. METHODS: The medical
      records of patients with pineoblastoma evaluated at the M.D. Anderson Cancer
      Center between 1982 and 2012 were reviewed retrospectively. RESULTS: Thirty-one
      patients with medical records suitable for review were identified. The majority
      of patients were female (67.7%) with a median age at diagnosis of 18.2 years
      (range, 0.3-52.8 years). Twenty-one patients underwent surgical resection,
      recorded as gross total (n = 9) or subtotal (n = 12) resections. Thirty patients
      received radiation with photon-based therapy (n = 16), proton-based therapy (n =
      13), or radiosurgery (n = 1) to a median craniospinal irradiation dose of 36 Gy
      (range, 23.4-40 Gy) and a median focal dose of 54 Gy (range, 40-58.4 Gy). Twenty
      eight patients received chemotherapy before (n = 10), during (n = 10), and after
      (n = 22) radiation. Median overall survival was 8.7 years for the entire cohort,
      with 2-, 5-, and 10- year actuarial rates of 89.5%, 69.4%, and 48.6%,
      respectively. Median disease-free survival was 10 years with 2-, 5-, and 10- year
      actuarial rates of 84.3%, 62.6%, and 55.7%, respectively. Univariate analysis
      failed to correlate age, sex, or extent of surgical resection with disease-free
      or overall survival. CONCLUSIONS: Modern, multimodality treatment of
      pineoblastoma yields a high rate of overall survival, with acceptable short- and
      long-term toxicity. A greater M-stage at presentation and development of disease
      recurrence correlate with worse overall survival. Patients who received focal
      radiation initially experienced a greater rate of disease recurrence compared
      with those treated to the craniospinal axis.

PMID- 25045789
TI  - Efficacy of FLOW 800 with indocyanine green videoangiography for the quantitative
      assessment of flow dynamics in cerebral arteriovenous malformation surgery.
AB  - OBJECTIVE: To evaluate the quantitative assessment of flow dynamics during
      surgery for arteriovenous malformations (AVMs) with FLOW 800 with indocyanine
      green videoangiography. METHODS: Changes in flow dynamics in the superficial AVM
      components (feeder, nidus, and drainer), the adjacent cortical artery, and the
      cortical vein surrounding AVM were evaluated. Analysis was performed at
      predissection, postclipping of the feeders, and postresection of the nidus with
      the use of quantitative values of the maximum fluorescence intensity, time to
      half-maximum fluorescence intensity (T1/2 FI), and the fluorescence intensity
      rate at T1/2 FI semiautomatically obtained with the use of FLOW 800 software.
      RESULTS: FLOW 800 assessments were performed in 7 cases. The time difference
      between the T1/2 FI, defined as transit time, in the cortical artery and the
      drainer was prolonged from 0.08 +/- 0.65 seconds to 2.63 +/- 1.79 seconds (P <
      0.0001) at postfeeder clipping phase. The transit time between the cortical
      artery and the cortical vein was reduced to 3.76 +/- 1.37 seconds at post feeder
      clipping phase (P = 0.024) and 2.63 +/- 0.80 seconds at final phase (P = 0.005)
      compared with 4.56 +/- 1.47 seconds at predissection phase. The maximum intensity
      and the fluorescence intensity rate at T1/2 FI were not significantly different
      at these phases, excluding the maximum intensity of the drainer decreasing from
      533 +/- 271 to 399 +/- 217 (P = 0.006) at post feeder clipping phase. CONCLUSION:
      FLOW 800 analysis with indocyanine green videoangiography provides the real-time
      hemodynamic status of the AVMs and adjacent brain at various stages of resection.
      This technique is feasible to resect AVMs more safely and convincingly.

PMID- 25045790
TI  - Nonglomic tumors of the jugular foramen: differential diagnosis and prognostic
      implications.
AB  - OBJECTIVE: Tumors of the jugular foramen are notably rare, and the majority of
      them arise from the glomic tissue of the jugular vein. There are other tumors
      that do not originate from that tissue, and these are called the nonglomic
      tumors. This report includes a series of patients with nonglomic tumors of the
      jugular foramen to analyze their biological and radiological behavior and the
      clinical outcomes of patients. METHODS: Patients with tumors of the jugular
      foramen other than chemodectomas were included for the present series. All of the
      patients were subjected to a protocol that included imaging studies and a
      complete clinical evaluation. Surgery was planned and performed by a
      multidisciplinary team using the following approaches: retrosigmoid,
      infratemporal fossa, and zygomatic-transmandibular. Depending on the precise
      diagnosis and surgical outcomes, radiotherapy or radiosurgery were indicated. The
      average follow-up period was 5 years. RESULTS: Thirty patients with nonglomic
      tumors were included: 18 schwannomas, 6 meningiomas, 5 chordomas, and 1
      metastatic carcinoma. The patients with chordomas had the most severe clinical
      manifestations, and the chordomas were the largest and most invasive tumors that
      destroyed the jugular foramen contour on imaging studies. Schwannomas presented a
      more benign clinical evolution and enlarged (but did not destroy) the jugular
      foramen contour. Two patients died (chordomas) during the follow-up because of
      tumor activity. CONCLUSIONS: The most common nonglomic tumor of the jugular
      foramen was the schwannoma, which was the lesion with the best surgical
      prognosis. Chordoma is a rare and highly destructive tumor that has a notably
      high recurrence index.

PMID- 25045791
TI  - Utility of early postoperative high-resolution volumetric magnetic resonance
      imaging after transsphenoidal pituitary tumor surgery.
AB  - OBJECTIVE: Controversy exists over the utility of early postoperative magnetic
      resonance imaging (MRI) after transsphenoidal pituitary surgery for
      macroadenomas. We investigate whether valuable information can be derived from
      current greater resolution scans. METHODS: Volumetric MRI scans were obtained in
      the early (<10 days) and late (>30 days) postoperative periods in a series of
      patients undergoing transsphenoidal pituitary surgery. The volume of the residual
      tumor, resection cavity, and corresponding visual field tests were recorded at
      each time point. Statistical analyses of changes in tumor volume and cavity size
      were calculated using the late MRI as the gold standard. RESULTS: A total of 40
      patients met the inclusion criteria. Preoperative tumor volume averaged 8.8
      cm(3). Early postoperative assessment of average residual tumor volume (1.18
      cm(3)) was quite accurate and did not differ statistically from late
      postoperative volume (1.23 cm(3), P = 0.64), indicating the utility of early
      scans to measure residual tumor. Early scans were 100% sensitive and 91% specific
      for predicting >= 98% resection (P < 0.001, Fisher exact test). The average
      percent decrease in cavity volume from preoperative MRI (tumor volume) to early
      postoperative imaging was 45% with decreases in all but 3 patients. There was no
      correlation between the size of the early cavity and the visual outcome.
      CONCLUSIONS: Early, high-resolution volumetric MRI is valuable in determining the
      presence or absence of residual tumor. Cavity volume almost always decreases
      after surgery, and a lack of decrease should alert the surgeon to possible
      persistent compression of the optic apparatus that may warrant reoperation.

PMID- 25045792
TI  - The peculiar cystic vestibular schwannoma: a single-center experience.
AB  - OBJECTIVE: The operative management of cystic vestibular schwannoma is more
      challenging. In this study, we focus on the peculiarity of cystic vestibular
      schwannoma in terms of management and outcome. We evaluated a homogenous series
      of consecutive patients with cystic vestibular schwannomas who were operated on
      with a similar technique and via the same surgical approach. METHODS: The
      patients with vestibular schwannoma who were operated at our center from 2000 to
      2012 were retrospectively analyzed. Those having cystic vestibular schwannomas,
      recognized by the presence of cystic components both on the preoperative magnetic
      resonance imaging and intraoperatively, were included. Thirty-seven consecutive
      patients matched the inclusive criteria. The whole pool of solid vestibular
      schwannomas with similar tumor extension was used as a control group. The facial
      nerve outcome is reported early after surgery and after 1-year follow-up. Facial
      nerve palsy GI-III according to House-Brackmann grading system was considered a
      favorable outcome. Facial nerve palsy GIV-VI was considered unfavorable. The
      surgical morbidity in the 2 groups was compared. A special point of interest was
      the correlation between the cyst pattern and outcome. RESULTS: Cystic vestibular
      schwannomas are associated with a worse early facial nerve outcome (unfavorable
      in 37.8% in cystic vestibular schwannoma compared with 17.5% in the solid
      variant). After 1-year follow-up, 8.1% of the cystic variant had unfavorable
      facial nerve outcome. Meanwhile, 6.2% of the solid variant had unfavorable
      outcomes. There was no statistically significant difference between both groups
      regarding the long-term facial nerve outcome. The cystic variant had a greater
      postoperative morbidity rates, especially hemorrhage (8.1%), in comparison with
      solid vestibular schwannoma of the same extension (1.7%). Hydrocephalus without
      significant hematoma is also significantly greater in the cystic type than the
      solid variant. Medially located thin walled cysts are related to worse facial
      nerve outcome. CONCLUSION: Surgery of cystic vestibular schwannomas is associated
      with a greater rate of morbidity and facial nerve dysfunction compared with the
      solid variant. Special attention is required during facial dissection to allow
      functional preservation, especially with tumors with medially located thin walled
      cysts. Meticulous hemostasis also is required to avoid postoperative hematoma.
      Close postoperative care is mandatory for early detection and prompt management
      of possible postoperative complications.

PMID- 25045793
TI  - Adsorption of multiple spherical particles onto sinusoidally corrugated
      substrates.
AB  - We utilize a Monte Carlo simulation scheme based on the bond fluctuation model to
      simulate settlement of adhesive particles onto sinusoidally corrugated
      substrates. The particles are composed of a hard inner core with either an
      effective potential shell or a "soft" adhesive shell made of flexible arms
      attached to the particle surface. These chains adhere via either the effective
      potential shell or the sticky chain ends to the surface via pairwise nonspecific
      interactions. This simulation model allows for multiple particles to settle onto
      each tested substrate to elucidate the behavior of the collective adhesive layer
      featuring multiparticle assembly. Particles move within a 3D lattice space and
      settle on the substrate due to attractive particle/substrate interactions. Once a
      single particle adheres to the substrate, a new particle is introduced into the
      lattice to begin a new settlement. Through this multiparticle settlement mode, we
      explore the interplay among the characteristics of the particles (i.e., size,
      interaction shell) and the substrates (i.e., wavelength and periodicity) as well
      as interparticle interactions. We report that the adhesion of particles with an
      effective interaction shell to the substrates is reduced dramatically when the
      particle size is smaller than the feature width of the periodic substrate. The
      settlement of particles with flexible hair on the sinusoidally corrugated
      substrates is more complex. Specifically, the presence of flexible polymeric
      hairs makes the particle settlement more likely to occur on nearly all substrates
      studied irrespective of the characteristics of the substrate. 

PMID- 25045794
TI  - Autonomous and controlled motivation for eating disorders treatment: baseline
      predictors and relationship to treatment outcome.
AB  - OBJECTIVE: This study aimed to identify baseline predictors of autonomous and
      controlled motivation for treatment (ACMT) in a transdiagnostic eating disorder
      sample, and to examine whether ACMT at baseline predicted change in eating
      disorder psychopathology during treatment. METHOD: Participants were 97
      individuals who met DSM-IV-TR criteria for an eating disorder and were admitted
      to a specialized intensive treatment programme. Self-report measures of eating
      disorder psychopathology, ACMT, and various psychosocial variables were completed
      at the start of treatment. A subset of these measures was completed again after
      3, 6, 9, and 12 weeks of treatment. RESULTS: Multiple regression analyses showed
      that baseline autonomous motivation was higher among patients who reported more
      self-compassion and more received social support, whereas the only baseline
      predictor of controlled motivation was shame. Multilevel modelling revealed that
      higher baseline autonomous motivation predicted faster decreases in global eating
      disorder psychopathology, whereas the level of controlled motivation at baseline
      did not. CONCLUSION: The current findings suggest that developing interventions
      designed to foster autonomous motivation specifically and employing autonomy
      supportive strategies may be important to improving eating disorders treatment
      outcome. PRACTITIONER POINTS: The findings of this study suggest that developing
      motivational interventions that focus specifically on enhancing autonomous
      motivation for change may be important for promoting eating disorder recovery.
      Our results lend support for the use of autonomy supportive strategies to
      strengthen personally meaningful reasons to achieve freely chosen change goals in
      order to enhance treatment for eating disorders. One study limitation is that
      there were no follow-up assessments beyond the 12-week study and we therefore do
      not know whether the relationships that we observed persisted after treatment.
      Another limitation is that this was a correlational study and it is therefore
      important to be cautious about making causal conclusions when interpreting the
      results.

PMID- 25045795
TI  - Is a retention time after the instillation of anesthetic lubricant necessary when
      performing male flexible cystoscopy?
AB  - OBJECTIVE: Flexible cystoscopy is a common practice in urology. We wanted to
      determine whether a retention time of 5 minutes between the administration of a
      local anesthetic lubricant and flexible cystoscope insertion decreased the degree
      of discomfort or pain in the patient. MATERIALS AND METHODS: Males who underwent
      flexible cystoscopy during 5 months were randomized in a prospective study. They
      were divided into two groups. In the first one, the Cathejell lubricant with
      lidocaine 12.5 g was administered and cystoscopy was performed immediately. In
      the second one, the same lubricant was maintained in the urethra for 5 minutes
      before the performance of cystoscopy. After scanning, all the patients were
      requested to indicate the degree of perceived pain on a visual pain scale from 0
      to 10, with 0 being no discomfort and 10 being the maximum degree of pain
      bearable. As a secondary objective, the relationship of pain to age and to the
      type of cystoscopist (urologist/resident doctor) was studied. For statistical
      analysis, a Student's t-test for independent samples and correlation analysis
      were used. RESULTS: A total of 242 patients were studied, 110 in the immediate
      group and 132 in the 5-minute delay group, with samples being homogeneous for the
      age and type of cystoscopist. The mean in the pain scale in the immediate group
      was 2.41, and in the 5-minute delay group was 2.04, with no significant
      differences between them (p=0.175). There was no relationship with age (r=-0.061,
      p=0.348) or with the type of cystoscopist (2.06 of average pain in the associate
      group, 2.35 in the resident, p=0.28). CONCLUSIONS: There is no benefit in waiting
      a short time after the administration of intraurethral lubrication with a local
      anesthetic in flexible cystoscopy in men. There is also no relationship between
      the patient age or the type of cystoscopist (urologist/resident doctor) and
      perceived pain.

PMID- 25045796
TI  - Serum anti-Mullerian hormone and insulin resistance in the main phenotypes of non
      obese polycystic ovarian syndrome women in China.
AB  - OBJECTIVES: Objective was to evaluate anti-Mullerian-hormone (AMH) and parameters
      for insulin resistance (IR) in the main phenotypes of polycystic ovarian syndrome
      (PCOS), and to investigate their correlation for the first time in non-obese
      Chinese women. METHODS: Within this prospective study, 160 PCOS cases and 40
      healthy women, matched by age and BMI, were included. In four groups (n = 40)
      according to the four phenotypes of PCOS by definition of the National Institute
      of Health (2012), AMH, ovarian volume and number of follicles 2-9 mm were
      assessed as well as insulin resistance indexes (Homeostatic Model Assessment)
      (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: AMH
      levels were higher in PCOS than in controls, with differences comparing the
      phenotypes, highest in the group with all three criteria for PCOS. However, for
      HOMA-IR and QUICKI and correlation to AMH no significant differences were found.
      CONCLUSIONS: AMH is a useful parameter to assess in the different phenotypes the
      severity of PCOS, and to compare with healthy women, for the first time
      demonstrated in Chinese patients. In contrast, the parameters for IR and their
      relation to AMH did not show clear differences comparing the four phenotypes, and
      need further investigation.

PMID- 25045797
TI  - Transport properties for systems with deep potential wells: H + O2.
AB  - Transport properties for collisions of the oxygen molecule with hydrogen atoms
      are computed by means of quantum scattering calculations. Because two potential
      energy surfaces (PESs) arise from the interaction of H(2S) with O2(X3Sigmag+),
      namely 2A" and 4A", collision integrals were computed using both PESs and then
      averaged with weighting by their respective spin multiplicities. A PES for the
      4A" state was computed for the interaction of O2, frozen at its equilibrium
      internuclear separation, with a hydrogen atom, using a coupled-cluster method
      that includes all single and double excitations as well as perturbative
      contributions of connected triple excitation. A PES of similar quality was taken
      from Klos et al. [J. Chem. Phys.2008, 129, 064306] for the 2A" state. Because the
      2A" state correlates with the deep HO2(X2A") well, statistical capture boundary
      conditions [Rackham et al., J. Chem. Phys.2003, 119, 12895] were applied to
      compute the S matrix, and then the transport properties, for this state.

PMID- 25045798
TI  - Race and gender disparities in nutrient intake are not related to metabolic
      syndrome in 20- to 59-year-old US adults.
AB  - BACKGROUND: The goal of this study was to examine the relationship between
      macronutrient and micronutrient intake and metabolic syndrome within race and
      gender cohorts of young US adults. METHODS: The 2007-2010 National Health and
      Nutrition Examination Survey (NHANES) data for adults (n=2440) aged 20-59 were
      analyzed. Two 24-hr dietary recalls were used to measure intake of total
      calories, macronutrients, and 20 vitamins and minerals. Metabolic syndrome and
      its components were defined by the National Heart, Lung and Blood Institute
      criteria. Differences in statistical tests were noted when significant at P<0.05.
      RESULTS: Prevalence of metabolic syndrome among 20- to 59-year-old adults was
      30.4% [95% confidence interval 27.6-33.2]. Among cohorts, metabolic syndrome was
      highest in black women and white men, and lowest in black men and white women.
      Regression analysis indicated that no macronutrients were associated with greater
      risk of metabolic syndrome. For relative macronutrient intake, men with metabolic
      syndrome consumed more polyunsaturated fats, whereas women with metabolic
      syndrome consumed more total, saturated and monounsaturated fats and less fiber
      and starch than women without metabolic syndrome. Among races, white men and
      women consumed greater absolute quantities of all macronutrients except
      carbohydrates and sugar. Micronutrient intake was greatest for white men and
      women; women without metabolic syndrome had greater micronutrient adequacy than
      women with metabolic syndrome. CONCLUSION: Nutrient intake varied between
      race/gender cohorts; however, there were few clinically significant differences
      in nutrient intake between those with and without metabolic syndrome. Diet may be
      marginally related to diagnosis of metabolic syndrome.

PMID- 25045799
TI  - Upshift of phase transition temperature in nanostructured PbTiO3 thick film for
      high temperature applications.
AB  - Thick polycrystalline pure PbTiO3 films with nano size grains were synthesized
      for the first time by aerosol deposition. Annealed 7 MUm thick films exhibit well
      saturated ferroelectric hysteresis loops with a remanent polarization and
      coercive field of 35 MUC/cm(2) and 94 kV/cm, respectively. A large-signal
      effective d33,eff value of >60 pm/V is achieved at room temperature. The measured
      ferroelectric transition temperature (Tc) of the films ~550  degrees C is >50 
      degrees C higher than the reported values (~490  degrees C) for PbTiO3 ceramics.
      First-principles calculations combined with electron energy loss spectroscopy
      (EELS) and structural analysis indicate that the film is composed of nano size
      grains with slightly decreased tetragonality. There is no severe off
      stoichiometry, but a high compressive in-plane residual stress was observed in
      the film along with a high transition temperature and piezoelectric response. The
      ferroelectric characteristics were sustained until 200  degrees C, providing
      significant advancement toward realizing high temperature piezoelectric
      materials. 

PMID- 25045800
TI  - Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for
      the pathogenesis of Parkinson's disease.
AB  - The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified
      mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl
      potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum
      and in vitro in PC12 cells and human cultured fibroblasts and glial cells. The in
      vivo results resemble those noted previously with knockouts of the genes encoding
      ALDH1A1 and 2, a mouse model of aging-related Parkinson's disease (PD). Exposure
      to pesticides that inhibit ALDH may therefore increase PD risk via DOPAL buildup.
      This study lends support to the "catecholaldehyde hypothesis" that the autotoxic
      dopamine metabolite DOPAL plays a pathogenic role in PD. 

PMID- 25045801
TI  - Tooth discoloration induced by endodontic phenothiazine dyes in photodynamic
      therapy.
AB  - OBJECTIVE: This study sought to assess if discoloration of tooth structures
      occurs after photodynamic therapy (PDT) and to determine the efficacy of a
      protocol to remove the photosensitizers. BACKGROUND DATA: PDT has been used in
      root canal treatment to enhance cleaning and disinfection of the root canal
      system. PDT uses a low power laser in association with a dye as a
      photosensitizer. Photosensitizers can induce staining of the dental structures,
      resulting in an unaesthetic appearance. METHODS: Forty teeth were randomly
      divided into four groups according to the photosensitizer used and pre
      irradiation time: 0.01% methylene blue for 5 min (MB5); 0.01% methylene blue for
      10 min (MB10); 0.01% toluidine blue for 5 min (TB5); and 0.01% toluidine blue for
      10 min (TB10). Specimens were irradiated with a 660 nm diode laser with a 300 MUm
      diameter optical fiber, at 40 mW power setting for 3 min. Immediately after, the
      photosensitizers were removed with Endo-PTC cream+2.5% sodium hypochlorite
      (NaOCl). The shade was measured by a Vita Easyshade spectrophotometer based on
      the CIELAB color system (L*a*b* values) at three different experimental times:
      before PDT (T0), immediately after PDT (T1), and after removal of the
      photosensitizer (T2). RESULTS: The results showed a decrease in the averages of
      the L*a*b* coordinate values after PDT (T1) in all the groups, when compared with
      the number at T0, with a significant statistical difference in group MB10. After
      photosensitizer removal (T2), all the values of the coordinates increased with
      significant statistical differences (p<0.05) between T1 and T2 in L* and a*.
      CONCLUSIONS: It can be concluded that both methylene blue and toluidine blue dyes
      cause tooth discoloration, and that Endo-PTC cream associated with 2.5% NaOCl
      effectively remove these dyes, regardless of the pre-irradiation time used for
      PDT.

PMID- 25045802
TI  - Flame retardants and legacy chemicals in Great Lakes' water.
AB  - The Great Lakes have been the focus of extensive environmental research, but
      recent data on the aquatic concentrations of emerging compounds, such as flame
      retardants, are scarce. Water samples from 18 stations on the five Great Lakes
      were collected in 2011 and 2012 using XAD-2 resin adsorption and analyzed for
      PCBs, organochlorine pesticides, PAHs, polybrominated diphenyl ethers (PBDEs),
      and emerging flame retardants, including organophosphate flame retardants (OPEs).
      Total PCB concentrations ranged from 117 +/- 18 pg/L in Lake Superior to 623 +/-
      113 pg/L in Lake Ontario. Among the organochlorine pesticides, the most abundant
      was dieldrin, with the highest average concentration of 99 +/- 26 pg/L in Lake
      Erie, followed by p,p'-DDD with an average concentration of 37 +/- 8 pg/L in Lake
      Ontario. Total PAH concentrations were higher in Lakes Erie and Ontario than in
      Lakes Michigan, Huron, and Superior. Total PBDE concentrations were highest in
      Lake Ontario (227 +/- 75 pg/L), and the most abundant congeners were BDE-47, BDE
      99, and BDE-209. Total OPE concentrations ranged between 7.3 +/- 4.5 ng/L in Lake
      Huron to 96 +/- 43 ng/L in Lake Erie. 

PMID- 25045804
TI  - Therapeutic responses to different anti-Trypanosoma cruzi drugs in experimental
      infection by benznidazole-resistant parasite stock.
AB  - SUMMARY This study describes the role of parasite clearance time induced by
      benznidazole, fexinidazole and posaconazole treatments upon mice infection with a
      benznidazole-resistant Trypanosoma cruzi strain in the pathological outcomes.
      Trypanosoma cruzi-infected mice were treated with different drugs and parasite
      clearance time was detected by blood and tissue qPCR, to determine the dynamic
      relationship between the efficacy of the treatments and the intensity of heart
      lesion/serum inflammatory mediators. Our results indicate that anti-T. cruzi
      treatments were able to reduce parasite replication and consequently induce
      immunomodulatory effects, where the degree of the immunopathology prevention was
      related to the time of parasite clearance induced by different treatments.
      Nevertheless, in benznidazole and posaconazole treatments, parasite rebounding
      was detected with parasitism reaching levels similar to infected and non-treated
      mice; the time for parasitic rebound being earlier among benznidazole-treated
      mice. In parallel, an increase of cardiac lesions and plasma chemokine levels was
      also detected and was more accentuated in benznidazole-treated animals.
      Interestingly, in the presence of parasitological cure (fexinidazole treatment),
      basal levels of these inflammatory mediators were evidenced as well as an absence
      of cardiac inflammation or fibrosis. Overall, our data indicate that all
      treatments have positive effects on the clinical evolution of T. cruzi infection,
      with success in preventing cardiac alterations being drug-dependent.

PMID- 25045803
TI  - Development of self-report measures of social attitudes that act as environmental
      barriers and facilitators for people with disabilities.
AB  - OBJECTIVE: To describe the development of new self-report measures of social
      attitudes that act as environmental facilitators or barriers to the participation
      of people with disabilities in society. DESIGN: A mixed-methods approach included
      a literature review; item classification, selection, and writing; cognitive
      interviews and field testing of participants with spinal cord injury (SCI),
      traumatic brain injury (TBI), or stroke; and rating scale analysis to evaluate
      initial psychometric properties. SETTING: General community. PARTICIPANTS:
      Individuals with SCI, TBI, or stroke participated in cognitive interviews (n=9);
      community residents with those same conditions participated in field testing
      (n=305). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Self-report item pool of
      social attitudes that act as facilitators or barriers to people with disabilities
      participating in society. RESULTS: An interdisciplinary team of experts
      classified 710 existing social environment items into content areas and wrote 32
      new items. Additional qualitative item review included item refinement and
      winnowing of the pool prior to cognitive interviews and field testing of 82
      items. Field test data indicated that the pool satisfies a 1-parameter item
      response theory measurement model and would be appropriate for development into a
      calibrated item bank. CONCLUSIONS: Our qualitative item review process supported
      a social environment conceptual framework that includes both social support and
      social attitudes. We developed a new social attitudes self-report item pool.
      Calibration testing of that pool is underway with a larger sample to develop a
      social attitudes item bank for persons with disabilities.

PMID- 25045805
TI  - Immunogenicity of recombinant VP2 proteins of all nine serotypes of African horse
      sickness virus.
AB  - African horse sickness (AHS) is an equine disease with a mortality of up to 90%
      for susceptible horses. The causative agent AHS virus (AHSV) is transmitted by
      species of Culicoides. AHSV serogroup within the genus Orbivirus of the
      Reoviridae family consists of nine serotypes that show no or very limited cross
      neutralization. Of the seven structural proteins (VP1-VP7) of AHSV, VP2 is the
      serotype specific protein, and the major target for neutralizing antibodies. In
      this report, recombinant VP2 proteins of all nine serotypes were expressed
      individually by the baculovirus expression system and the immunogenicity of each
      was studied by immunization of guinea pigs with single VP2 as well as with
      cocktails of VP2 proteins. Homologous neutralizing antibodies measured by 50%
      plaque reduction assay showed varying degrees (from 37 to 1365) of titers for
      different VP2 proteins. A low cross-neutralizing antibody titer was found for
      genetically related AHSV serotypes. Immunization with VP2 cocktails containing
      equal amounts of each of the VP2 proteins also triggered neutralizing antibodies
      albeit to lower titers (4-117) to each of the serotypes in the cocktail. This
      study is a first step to develop a VP2 subunit vaccine for AHS and our results
      indicate that VP2 subunit vaccines are feasible individually or in a multi
      serotype cocktail.

PMID- 25045806
TI  - Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1)
      2009 vaccine: results from a double-blinded, randomized Phase I clinical trial in
      healthy Asian volunteers.
AB  - METHODS: A novel, fully bacterially produced recombinant virus-like particle
      (VLP) based influenza vaccine (gH1-Qbeta) against A/California/07/2009(H1N1) was
      tested in a double-blind, randomized phase I clinical trial at two clinical sites
      in Singapore. The trial evaluated the immunogenicity and safety of gH1-Qbeta in
      the presence or absence of alhydrogel adjuvant. Healthy adult volunteers with no
      or low pre-existing immunity against A/California/07/2009 (H1N1) were randomized
      to receive two intramuscular injections 21 days apart, with 100MUg vaccine,
      containing 42MUg hemagglutinin antigen. Antibody responses were measured before
      and 21 days after each immunization by hemagglutination inhibition (HAI) assays.
      The primary endpoint was seroconversion on Day 42, defined as percentage of
      subjects which reach a HAI titer >=40 or achieve an at least 4-fold rise in HAI
      titer (with pre-existing immunity). The co-secondary endpoints were safety and
      seroconversion on Day 21. RESULTS: A total of 84 Asian volunteers were enrolled
      in this study and randomized to receive the adjuvanted (n=43) or the non
      adjuvanted (n=41) vaccine. Of those, 43 and 37 respectively (95%) completed the
      study. There were no deaths or serious adverse events reported during this trial.
      A total of 535 adverse events occurred during treatment with 49.5% local
      solicited symptoms, of mostly (76.4%) mild severity. The most common treatment
      related systemic symptom was fatigue. The non-adjuvanted vaccine met all primary
      and secondary endpoints and showed seroconversion in 62.2% and 70.3% of
      participants respectively on Day 21 and Day 42. While the adjuvanted vaccine
      showed an increased seroconversion from 25.5% (Day 21) to 51.2% (Day 42), it did
      not meet the immunogenicity endpoint. CONCLUSION: In summary, non-adjuvanted gH1
      Qbeta showed similar antibody mediated immunogenicity and a comparable safety
      profile in healthy humans to commercially available vaccines. These results
      warrant the consideration of this VLP vaccine platform for the vaccination
      against influenza infection (HSA CTC1300092).

PMID- 25045807
TI  - Optic neuritis following Varicella zoster vaccination: report of two cases.
AB  - Two women presented at our clinic with vision blurring following Varicella zoster
      virus (VZV) vaccination, 3 weeks and 1 week ago. Ophthalmologic examination and
      magnetic resonance imaging revealed bilateral and unilateral optic neuritis,
      respectively. One patient had a history of optic neuritis in the fellow eye 33
      years ago without recurrence since then. Both patients completely recovered after
      treatment with high dose intravenous methylprednisolone followed by a tapered
      dose of oral prednisolone. This is the first report of optic neuritis occurring
      in relation to VZV vaccination. 

PMID- 25045808
TI  - Monovalent H1N1 influenza vaccine safety in pregnant women, risks for acute
      adverse events.
AB  - OBJECTIVE: To assess risks for acute adverse events and pregnancy complications
      in pregnant women following monovalent 2009 H1N1 inactivated influenza (MIV)
      vaccination. METHODS: Within the Vaccine Safety Datalink, we compared rates of
      pre-specified medically attended events (MAE) occurring within 42 days of MIV
      vaccination to those occurring in matched cohorts that at the same gestational
      age were either unvaccinated or received seasonal trivalent inactivated influenza
      (TIV) vaccine. Using generalized estimating equation method, with a Poisson
      distribution and log link, we calculated adjusted incident rate ratios (AIRR).
      RESULTS: Among 9349 women receiving MIV in any trimester, only one MAE occurred 0
      3 days following MIV, an allergic reaction. No cases of Guillain-Barre syndrome,
      Bell's palsy, or transverse myelitis occurred 1-42 days after MIV. Compared to
      women receiving TIV and to unvaccinated women, risks for acute MAEs were not
      increased following MIV for any outcome. Hyperemesis was the most common adverse
      event in the MIV, TIV, and unvaccinated groups, occurring at a rate of about 4%
      over a 42-day period in all groups. Over a 42-day window, among all groups,
      incident gestational diabetes occurred at a rate of 3% and thrombocytopenia
      occurred at a rate of approximately 0.3%. Among women receiving MIV during
      pregnancy, increased risks for these and other less common obstetric events were
      not detected. CONCLUSION: In this large cohort of pregnant women no acute safety
      signals were identified within 6 weeks of receipt of MIV.

PMID- 25045809
TI  - HPAEC-PAD quantification of Haemophilus influenzae type b polysaccharide in
      upstream and downstream samples.
AB  - Due to the rapidly increasing introduction of Haemophilus influenzae type b (Hib)
      and other conjugate vaccines worldwide during the last decade, reliable and
      robust analytical methods are needed for the quantitative monitoring of
      intermediate samples generated during fermentation (upstream processing, USP) and
      purification (downstream processing, DSP) of polysaccharide vaccine components.
      This study describes the quantitative characterization of in-process control
      (IPC) samples generated during the fermentation and purification of the capsular
      polysaccharide (CPS), polyribosyl-ribitol-phosphate (PRP), derived from Hib.
      Reliable quantitative methods are necessary for all stages of production;
      otherwise accurate process monitoring and validation is not possible. Prior to
      the availability of high performance anion exchange chromatography methods, this
      polysaccharide was predominantly quantified either with immunochemical methods,
      or with the colorimetric orcinol method, which shows interference from
      fermentation medium components and reagents used during purification. Next to an
      improved high performance anion exchange chromatography-pulsed amperometric
      detection (HPAEC-PAD) method, using a modified gradient elution, both the orcinol
      assay and high performance size exclusion chromatography (HPSEC) analyses were
      evaluated. For DSP samples, it was found that the correlation between the results
      obtained by HPAEC-PAD specific quantification of the PRP monomeric repeat unit
      released by alkaline hydrolysis, and those from the orcinol method was high
      (R(2)=0.8762), and that it was lower between HPAEC-PAD and HPSEC results.
      Additionally, HPSEC analysis of USP samples yielded surprisingly comparable
      results to those obtained by HPAEC-PAD. In the early part of the fermentation,
      medium components interfered with the different types of analysis, but
      quantitative HPSEC data could still be obtained, although lacking the specificity
      of the HPAEC-PAD method. Thus, the HPAEC-PAD method has the advantage of giving a
      specific response compared to the orcinol assay and HPSEC, and does not show
      interference from various components that can be present in intermediate and
      purified PRP samples. 

PMID- 25045810
TI  - Human papillomavirus (HPV) vaccination and subsequent sexual behaviour: evidence
      from a large survey of Nordic women.
AB  - OBJECTIVE: To assess whether recipients and non-recipients of the human
      papillomavirus (HPV) vaccine subsequently differ in terms of sexual risk taking
      behaviour. DESIGN: Cross-sectional survey. Sequential analyses constructed from
      self-reported age at vaccination, age at first intercourse and age at response.
      SETTING: A random selection of women aged 18-46 years living in Denmark, Norway
      and Sweden in 2011-2012, eligible for opportunistic or organized catch-up HPV
      vaccination. PARTICIPANTS: A total of 3805 women reported to have received the
      HPV vaccine and 40,247 reported not to have received it. Among vaccinees, 1539
      received the HPV vaccine before or at the same age as sexual debut, of which 476
      and 1063 were eligible for organized catch-up and opportunistic vaccination,
      respectively. MAIN OUTCOME MEASURES: Self-reported sexual behaviour, compared by
      hazard ratios and odds ratios for women who received the HPV vaccine before or at
      the same age as sexual debut versus women who did not receive the HPV vaccine.
      RESULTS: HPV vaccination did not result in younger age at first intercourse.
      Women who received the HPV vaccine before or at the same age as sexual debut did
      not have more sexual partners than did non-vaccinees. Non-use of contraception
      during first intercourse was more common among non-vaccinees than among HPV
      vaccinees. The results were similar for organized catch-up and opportunistic
      vaccinees. CONCLUSION: Women who received the HPV vaccine before or at the same
      age as sexual debut did not subsequently engage more in sexual risk taking
      behaviour than women who did not receive the HPV vaccine.

PMID- 25045811
TI  - Active surveillance of adverse events following childhood immunization in
      Singapore.
AB  - INTRODUCTION: In Singapore, reporting of adverse events following immunization
      (AEFI) was historically passive. In 2009, Health Sciences Authority collaborated
      with KK Women's and Children's Hospital to perform active surveillance for AEFI.
      We report the methodology and initial findings of this surveillance following
      childhood vaccines. METHODS: From April 2010 to March 2012, we screened all
      paediatric admissions for possible relationships to vaccination, excluding
      elective admissions, and performed causality assessment for each case using
      standardized definitions for certain, probable, possible and unlikely. Baseline
      demographics, data on implicated vaccines and clinical details including severity
      and outcomes were collected. Total hospital admissions were used to calculate
      rates of AEFI. RESULTS: We screened 45,571 (80%) of 56,526 admissions, and
      evaluated 1988 (4.4%) children. Median age at presentation was 3.1 months, while
      median interval from vaccination to symptom onset was 6 days. There were 311
      (15.6%) children with AEFI that were considered possibly, probably or certainly
      associated with vaccines. However, 98.8% recovered without any long-term
      sequelae. The hospital-based active surveillance of AEFI enabled the detection of
      a 5-fold increase (95% CI 1.2-33.1) in BCG-associated regional lymphadenitis in
      April 2010, which triggered follow-up safety analysis to guide public health
      advice. CONCLUSIONS: Hospital-based active surveillance can enhance signal
      detection and follow-up investigations of AEFI. Subsequently, public health
      bodies are better equipped to maintain public confidence in vaccination
      programmes and physicians are able to provide relevant advice to parents. It also
      allows for a better understanding of risk-benefit ratios of specific vaccines and
      aids the generation of public health vaccination policy.

PMID- 25045812
TI  - Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit
      vaccine using SA-4-1BBL as a novel adjuvant.
AB  - The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V
      adjuvanted with alum. While alum generates Th2 regulated robust humoral
      responses, immune protection against Yersinia pestis has been shown to also
      involve Th1 driven cellular responses. Therefore, the rF1-V-based subunit vaccine
      may benefit from an adjuvant system that generates a mixed Th1 and humoral immune
      response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory
      molecule as a Th1 adjuvant to improve cellular responses generated by the rF1-V
      vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in
      generating CD4(+) and CD8(+) T cells producing TNFalpha and IFNgamma, signature
      cytokines for Th1 responses. The combination of SA-4-1BBL with alum further
      increased this Th1 response as compared with the individual adjuvants. Analysis
      of the humoral response revealed that SA-4-1BBL as a single adjuvant did not
      generate a significant Ab response against rF1-V, and SA-4-1BBL in combination
      with alum did not improve Ab titers. However, the combined adjuvants
      significantly increased the ratio of Th1 regulated IgG2c in C57BL/6 mice to the
      Th2 regulated IgG1. Finally, a single vaccination with rF1-V adjuvanted with SA-4
      1BBL+alum had better protective efficacy than vaccines containing individual
      adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the
      protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by
      generating a more balanced Th1 cellular and humoral immune response. As such,
      this adjuvant platform may prove efficacious not only for the rF1-V vaccine but
      also against other infections that require both cellular and humoral immune
      responses for protection.

PMID- 25045813
TI  - Costs of surviving meningococcal disease in Spain: evaluation for two cases of
      severe meningitis and septicaemia.
AB  - OBJECTIVES: The aim of this study was to count the lifelong rehabilitation costs
      associated with surviving meningococcal disease with major sequelae from the
      perspective of the Spanish National Healthcare System (NHS) and the national
      government. METHODS: Two severe scenarios describing meningococcal disease were
      developed, one case that represented meningococcal septicaemia and another case
      for meningococcal meningitis. The scenarios were developed based on a literature
      review on severe sequelae of meningococcal disease, and discussions with
      paediatricians who have been responsible for the treatment of children with this
      disease in Spain. Second, a detailed list of all health, educational and social
      care resources used by survivors during their acute illness and during the rest
      of their lives and by family members was obtained by interviewing survivors and
      their families. Professionals in health and social care were also interviewed to
      complete the list of resources and ensure the scenario's were accurate. The costs
      attributed to these resources were obtained from tariff lists, catalogues and
      published information by the national authorities. All costs were based on a life
      expectancy of a survivor of 70 years and expressed in EUR 2012. RESULTS: In this
      study it was estimated that the lifelong discounted rehabilitation costs
      associated with the treatment of long-term sequelae due to meningococcal disease
      are approximately ?1180,000-?1400,000. Medical care and social care were the main
      cost drivers for both septicaemia and meningitis. Annual costs showed to be the
      largest in the first year after diagnosis of the disease for both cases, due to
      high hospital admission and medical care costs during this period and decreased
      significantly over the years. CONCLUSION: This study shows that the lifelong
      rehabilitation costs associated with the survival of meningococcal disease with
      severe sequelae place an important burden on the NHS budget and governmental
      resources in Spain.

PMID- 25045814
TI  - Neutralizing and cross-neutralizing antibody titres induced by bivalent and
      quadrivalent human papillomavirus vaccines in the target population of organized
      vaccination programmes.
AB  - Aim of this investigator-initiated study was to evaluate and compare the titres
      of neutralizing and cross-neutralizing antibodies (NAbs) induced by the bivalent
      (Cervarix((r))) and quadrivalent (Gardasil((r))) HPV vaccines in a cohort of
      girls aged 11-13 years from organized vaccination programmes. To this aim, HPV16
      and HPV18 NAbs were measured by pseudovirion-based neutralization assays in serum
      collected at 1-6 months after the third vaccine dose in 107 girls vaccinated with
      Cervarix((r)) and 126 vaccinated with Gardasil((r)), while HPV31 and HPV45 cross
      NAbs were tested in the first 50 consecutive girls of both vaccine groups. The
      results of this study demonstrated that all vaccinated girls developed HPV16 and
      HPV18 NAbs, with the exception of two Gardasil((r)) vaccinees with undetectable
      HPV18 NAbs. Geometric mean titres (GMTs) of both HPV16 and HPV18 NAbs were
      significantly higher in Cervarix((r)) than in Gardasil((r)) vaccinees [HPV16 NAb
      GMT 22,136 (95% CI, 18,811-26,073) vs 5092 (4230-6151), respectively; P<0.0001;
      HPV18 NAb GMT 11,962 (9536-14,363) vs 1804 (1574-2110), respectively; P<0.0001].
      Cross-NAbs to HPV31 and HPV45 were detected more frequently Cervarix((r)) (HPV31
      NAb positivity rates 92.7% and 36%, respectively; P<0.05) than in Gardasil((r))
      vaccinees (HPV45 NAb positivity rates 56% and 6%, respectively; P<0.0001). The
      titres of cross-NAbs against HPV31 and HPV45 were also significantly higher in
      Cervarix((r)) than in Gardasil((r)) vaccinees [HPV31 NAb GMT 157.2 (95% CI, 92
      269) vs 13.0 (6.5-25.8), respectively; P<0.0001; HPV45 NAb GMT 4.7 (2.1-10.2) vs
      1.3 (0.3-3.1), respectively; P<0.01]. In conclusion, in adolescent girls
      vaccinated within organized vaccination programmes, HPV vaccines drive the
      generation not only of NAbs to HPV vaccine types, but also of cross-NAbs. The
      bivalent vaccine induced significantly higher HPV16 and HPV18 NAb titres and more
      frequently and at higher titre HPV31 and HPV45 cross-NAbs than the quadrivalent
      vaccine. 

PMID- 25045815
TI  - Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA)
      activity in a DNA prime-protein boost HIV-1 vaccine.
AB  - Recombinant protein vaccines are commonly formulated with an immune-stimulatory
      compound, or adjuvant, to boost immune responses to a particular antigen. Recent
      studies have shown that, through recognition of molecular motifs, receptors of
      the innate immune system are involved in the functions of adjuvants to generate
      and direct adaptive immune responses. However, it is not clear to which degree
      those receptors are also important when the adjuvant is used as part of a novel
      heterologous prime-boost immunization process in which the priming and boosting
      components are not the same type of vaccines. In the current study, we compared
      the immune responses elicited by a pentavalent HIV-1 DNA prime-protein boost
      vaccine in mice deficient in either Toll-like receptor 4 (TLR4) or myeloid
      differentiation primary response gene 88 (MyD88) to wildtype mice. HIV gp120
      protein administered in the boost phase was formulated with either monophosphoryl
      lipid A (MPLA), QS-21, or Al(OH)3. Endpoint antibody titer, serum cytokine
      response and T-cell memory response were assessed. Neither TLR4 nor MyD88
      deficiency had a significant effect on the immune response of mice given vaccine
      formulated with QS-21 or Al(OH)3. However, TLR4- and MyD88-deficiency decreased
      both the antibody and T-cell responses in mice administered HIV gp120 formulated
      with MPLA. These results further our understanding of the activation of TLR4 and
      MyD88 by MPLA in the context of a DNA prime/protein boost immunization strategy. 

PMID- 25045816
TI  - Safety, immunogenicity and efficacy of a recombinant tetravalent dengue vaccine:
      a meta-analysis of randomized trials.
AB  - The World Health Organization has stipulated a target: reduce the mortality rate
      caused by dengue disease by 50% until 2020. Most likely, this goal can be
      achieved by means of a dengue vaccine. Accordingly, the recombinant and
      tetravalent dengue vaccine (CYD-TDV), developed by the Sanofi Pasteur Group, is
      in an advanced stage of human testing. Although there are multiple randomized,
      placebo-controlled trials evaluating the CYD-TDV, individual results may have
      little power to identify differences between the populations studied. Thus, we
      conducted a meta-analysis to determine a more precise estimate of the overall
      parameters of safety, immunogenicity and efficacy of CYD-TDV. A data search was
      conducted in the PubMed, Medline, Cochrane Central Register of Controlled Trials
      and SciELO databases with defined selection criteria. We included for meta
      analysis seven randomized and placebo-controlled studies that included 6678
      patients randomized to receive the CYD-TDV (4586) or placebo (2092). Regarding
      vaccine safety, it was found that there was no significant difference between
      treated and placebo groups, as only approximately 5.5% of patients were withdrawn
      from the study. Regarding immunogenicity, the levels of neutralizing antibodies
      were measured by weighted mean differences (WMD), which were always higher in the
      vaccinated group (WMD/DENV1=59.7, 95% confidence interval [CI] 57-61;
      WMD/DENV2=99, 95% CI 95-102; WMD/DENV3=138, 95% CI 133-142; WMD/DENV4=123, 95% CI
      119-126). The clinical efficacy of the vaccine was 59% (95% CI 15-80; RR=0.41,
      95% CI 0.2-0.85, I(2)=30.9%). In conclusion, safety and a balanced immune
      response to the CYD-TDV were found. However, to fully establish the clinical
      effectiveness and robustness of immunogenicity, it is necessary to perform
      further studies to assess the long-term effects of the vaccine. 

PMID- 25045817
TI  - Development of an HIV vaccine attitudes scale to predict HIV vaccine
      acceptability among vulnerable populations: L.A. VOICES.
AB  - BACKGROUND: Decade-long delays in successful implementation of Hepatitis B
      vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of
      an implementation science approach to prepare for the effective translation of
      future HIV vaccines from clinical trials into routine practice. The objective of
      this study was to test HIV vaccine attitude items to develop reliable scales and
      to examine their association with HIV vaccine acceptability. METHODS: HIV vaccine
      attitude items were assessed as part of the L.A. VOICES survey, a large-scale
      study conducted among underserved residents of Los Angeles, to identify factors
      that may influence HIV vaccine acceptability. Participants (n=1225) were randomly
      selected from public STD clinics, needle exchange sites and Latino community
      clinics using three-stage, venue-based time space sampling. RESULTS: Exploratory
      factor analysis across 20 items revealed four distinct factors - mistrust, HIV
      vaccine social concerns, risk compensation, and altruistic vaccination - with
      acceptable reliability coefficients for each subscale (Cronbach's alpha range
      0.61-0.84). We found no significant differences in reliability by gender or by
      vaccine acceptability. Risk compensation (odds ratio (OR)=1.49; 95% CI=[1.18,
      1.89]; p=0.001) and altruistic vaccination (OR=1.40; 95% CI=[1.14, 1.71];
      p=0.001) were significantly and positively associated with HIV vaccine
      acceptability. CONCLUSIONS: We identified four HIV vaccine attitude scales with
      sound internal reliability parameters. In the aftermath of the first candidate
      vaccine to demonstrate efficacy against HIV infection, these scales may be
      helpful in bridging expectable research-to-practice gaps in future HIV vaccine
      dissemination among populations at risk. As HIV vaccine trials progress in the
      United States and globally, these measures also may be useful as a tool to assess
      and facilitate effective responses to community concerns about HIV vaccine trials
      and to target interventions to support recruitment and mitigate risk
      compensation.

PMID- 25045818
TI  - Influenza vaccine as prevention for cardiovascular diseases: possible molecular
      mechanism.
AB  - Despite plausible evidence for beneficial effects of the vaccination against
      influenza in cardiovascular diseases (CVD) very limited studies have been carried
      out to explain the molecular mechanism of this phenomenon. Using the
      informational spectrum method (ISM), a virtual spectroscopy method for analysis
      of protein-protein interactions, the bradykinin 2 receptor (BKB2R) was identified
      as a principal host protein which could mediate molecular processes underlying
      the cardioprotective effect of influenza vaccines. Based on this finding we
      suggest that some antibodies elicited by influenza vaccines act as agonists,
      which activate a BKB2R-associated signaling pathway contributing to the
      protection against CVD. The ISM analysis of 14 influenza viruses, which were used
      as components of seasonal vaccines, revealed four vaccine viruses
      A/Beijing/262/95(H1N1), A/NewCaledonia/20/1999(H1N1),
      A/Christchurch/28/2003(H3N2) and A/Perth/16/2009(H3N2), which could be suited
      best for further studies on the cardioprotective effect of influenza vaccines. 

PMID- 25045819
TI  - Cholera toxin B subunit-five-stranded alpha-helical coiled-coil fusion protein:
      "five-to-five" molecular chimera displays robust physicochemical stability.
AB  - To create a physicochemically stable cholera toxin (CT) B subunit (CTB), it was
      fused to the five-stranded alpha-helical coiled-coil domain of cartilage
      oligomeric matrix protein (COMP). The chimeric fusion protein (CTB-COMP) was
      expressed in Pichia pastoris, predominantly as a pentamer, and retained its
      affinity for the monosialoganglioside GM1, a natural receptor of CT. The fusion
      protein displayed thermostability, tolerating the boiling temperature of water
      for 10min, whereas unfused CTB readily dissociated to its monomers and lost its
      affinity for GM1. The fusion protein also displayed resistance to strong acid at
      pHs as low as 0.1, and to the protein denaturant sodium dodecyl sulfate at
      concentrations up to 10%. Intranasal administration of the fusion protein to mice
      induced anti-B subunit serum IgG, even after the protein was boiled, whereas
      unfused CTB showed no thermostable mucosal immunogenicity. This study
      demonstrates that CTB fused to a pentameric alpha-helical coiled coil has a novel
      physicochemical phenotype, which may provide important insight into the molecular
      design of enterotoxin-B-subunit-based vaccines and vaccine delivery molecules. 

PMID- 25045820
TI  - Modelling the epidemiological impact of rotavirus vaccination in Germany--a
      Bayesian approach.
AB  - BACKGROUND: Rotavirus (RV) infection is the primary cause of severe
      gastroenteritis in children aged <5 years in Germany and worldwide. In 2013 the
      German Standing Committee on Vaccination (STIKO) developed a national
      recommendation for routine RV-immunization of infants. To support informed
      decision-making we predicted the epidemiological impact of routine RV-vaccination
      in Germany using statistical modelling. METHODS: We developed a population-based
      model for the dynamic transmission of RV-infection in a vaccination setting.
      Using data from the communicable disease reporting system and survey records on
      the vaccination coverage from the eastern federal states, where the vaccine was
      widely used before recommended at national level, we first estimated RV vaccine
      effectiveness (VE) within a Bayesian framework utilizing adaptive Markov Chain
      Monte Carlo inference. The calibrated model was then used to compute the
      predictive distribution of RV-incidence after achieving high vaccination coverage
      with the introduction of routine vaccination. RESULTS: Our model estimated that
      RV-vaccination provides high protection against symptomatic RV-infection (VE=96%;
      95% credibility interval (CI): 91-99%) that remains at its maximum level for
      three years (95% CI: 1.43-5.80 years) and is fully waned after twelve years. At
      population level, routine vaccination at 90% coverage is predicted to reduce
      symptomatic RV-incidence among children aged <5 years by 84% (95% prediction
      interval (PI): 71-90%) including a 2.5% decrease due to herd protection. Ten
      years after vaccine introduction an increase in RV incidences of 12% (95% PI: -16
      to 85%) among persons aged 5-59 years and 14% (95% PI: -6 to 109%) within the age
      group >60 years was predicted. CONCLUSION: Routine infant RV-vaccination is
      predicted to considerably reduce RV-incidence in Germany among children <5 years.
      Our work generated estimates of RV VE in the field and predicted the population
      level impact, while adequately addressing the role of model and prediction
      uncertainty when making statements about the future.

PMID- 25045821
TI  - Issues and considerations in the use of serologic biomarkers for classifying
      vaccination history in household surveys.
AB  - Accurate estimates of vaccination coverage are crucial for assessing routine
      immunization program performance. Community based household surveys are
      frequently used to assess coverage within a country. In household surveys to
      assess routine immunization coverage, a child's vaccination history is classified
      on the basis of observation of the immunization card, parental recall of receipt
      of vaccination, or both; each of these methods has been shown to commonly be
      inaccurate. The use of serologic data as a biomarker of vaccination history is a
      potential additional approach to improve accuracy in classifying vaccination
      history. However, potential challenges, including the accuracy of serologic
      methods in classifying vaccination history, varying vaccine types and dosing
      schedules, and logistical and financial implications must be considered. We
      provide historic and scientific context for the potential use of serologic data
      to assess vaccination history and discuss in detail key areas of importance for
      consideration in the context of using serologic data for classifying vaccination
      history in household surveys. Further studies are needed to directly evaluate the
      performance of serologic data compared with use of immunization cards or parental
      recall for classification of vaccination history in household surveys, as well
      assess the impact of age at the time of sample collection on serologic titers,
      the predictive value of serology to identify a fully vaccinated child for multi
      dose vaccines, and the cost impact and logistical issues on outcomes associated
      with different types of biological samples for serologic testing. 

PMID- 25045822
TI  - Valuing vaccines using value of statistical life measures.
AB  - Vaccines are effective tools to improve human health, but resources to pursue all
      vaccine-related investments are lacking. Benefit-cost and cost-effectiveness
      analysis are the two major methodological approaches used to assess the impact,
      efficiency, and distributional consequences of disease interventions, including
      those related to vaccinations. Childhood vaccinations can have important non
      health consequences for productivity and economic well-being through multiple
      channels, including school attendance, physical growth, and cognitive ability.
      Benefit-cost analysis would capture such non-health benefits; cost-effectiveness
      analysis does not. Standard cost-effectiveness analysis may grossly underestimate
      the benefits of vaccines. A specific willingness-to-pay measure is based on the
      notion of the value of a statistical life (VSL), derived from trade-offs people
      are willing to make between fatality risk and wealth. Such methods have been used
      widely in the environmental and health literature to capture the broader economic
      benefits of improving health, but reservations remain about their acceptability.
      These reservations remain mainly because the methods may reflect ability to pay,
      and hence be discriminatory against the poor. However, willingness-to-pay methods
      can be made sensitive to income distribution by using appropriate income
      sensitive distributional weights. Here, we describe the pros and cons of these
      methods and how they compare against standard cost-effectiveness analysis using
      pure health metrics, such as quality-adjusted life years (QALYs) and disability
      adjusted life years (DALYs), in the context of vaccine priorities. We conclude
      that if appropriately used, willingness-to-pay methods will not discriminate
      against the poor, and they can capture important non-health benefits such as
      financial risk protection, productivity gains, and economic wellbeing.

PMID- 25045823
TI  - Seasonal influenza vaccination trends from 2007-2011 in privately insured
      children and adults in the United States.
AB  - BACKGROUND: To ensure adequate protection from seasonal influenza in the US, the
      Advisory Committee on Immunization Practices recommends vaccination of all
      persons aged 6 months or older, with rare exceptions. It also advises starting
      vaccination as soon as available and continuing throughout the influenza season.
      This study examined US seasonal vaccination trends during five consecutive
      influenza seasons in privately-insured children and adults. METHODS: This
      retrospective, observational cohort study examined trends in influenza
      vaccination during the 2007-2008 through 2011-2012 influenza seasons using
      administrative claims data from a large national insurer. RESULTS: The size of
      analysis population ranged from 1144,098 to 1245,487 (children, >=6 months-17
      years of age) and from 3931,622 to 4158,223 (adults, 18-64 years of age).
      Vaccination frequency increased through 2010-2011, was most frequent in young
      children, and decreased with age. Vaccination rates were highest in the Northeast
      and lowest in the West and were higher in individuals with frequent outpatient
      office visits than in those with no or rare visits, with larger differences seen
      in children. Between 2007 and 2011, the use of preservative-free inactivated
      vaccine increased, the use of multidose vaccines containing preservatives
      decreased, and the use of live attenuated influenza vaccines increased among
      children 2-17 years of age. From 2007-2008 through 2009-2010, the timing of
      vaccination each year began earlier than the previous one; it remained stable
      from 2009-2010 through 2011-2012. CONCLUSION: Annual influenza vaccination claims
      for privately-insured children and adults increased and shifted earlier from 2007
      through 2009-2011. During the 2011-2012 influenza season, 25.4% of children aged
      6 months-17 years and 12.3% of adults aged 18-64 years were vaccinated.
      Increasing influenza vaccination should remain a priority, and alternative venues
      for seasonal influenza vaccination should be considered in order to meet the
      Healthy People 2020 goal of 80% to 90% coverage among children.

PMID- 25045824
TI  - Safety, tolerability and immunogenicity of GS-4774, a hepatitis B virus-specific
      therapeutic vaccine, in healthy subjects: a randomized study.
AB  - BACKGROUND: GS-4774 is a recombinant, heat-killed, yeast-based immunotherapy
      engineered to express hepatitis B virus (HBV)-specific antigens. GS-4774 is being
      developed as a therapeutic vaccine for chronic HBV infection. The aim of this
      study was to assess the safety, tolerability and immunogenicity of GS-4774 in
      healthy subjects. DESIGN: This was a randomized, open-label, dose-ascending
      study. Subjects were allocated to one of three dose groups (n=20 per group) to
      receive 10, 40 or 80 yeast units (YU; 1YU=10(7) yeast) of GS-4774 in two
      immunization regimens (five subcutaneous injections at weekly intervals with one
      monthly booster or three subcutaneous injections at monthly intervals). T-cell
      mediated responses were determined by interferon (IFN)-gamma enzyme-linked
      immunospot (ELISpot) assay and lymphocyte-proliferation assay (LPA). RESULTS:
      Adverse events were reported by 39 of 60 (65%) subjects; all were mild or
      moderate and none was serious. Adverse events occurred most frequently in the
      highest dose group, 80YU, and the number of individual events was higher after
      weekly immunization than monthly. The most common adverse events were injection
      site reactions. Most (88%) subjects responded to GS-4774 by at least one of the T
      cell assays. Following immunization with GS-4774, IFN-gamma-producing T-cells
      specific for HBV antigens were detectable in 30 (51%) subjects. The ELISpot
      response was observed at all doses, with the highest frequency of responders
      occurring at the highest dose (10YU: 45%; 40YU: 35%; 80YU: 74%). Proliferative
      responses to HBV recombinant antigens were observed in 90% subjects; responses
      were mainly independent of GS-4774 dose and immunization regimen. CONCLUSIONS: GS
      4774 was safe and well-tolerated in healthy subjects with injection-site
      reactions being the most frequently reported adverse events. With both weekly and
      monthly regimens, GS-4774 provided HBV-specific immune responses at all doses
      evaluated. Further evaluation of GS-4774 is ongoing in patients with chronic HBV
      infection. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov (NCT01779505).

PMID- 25045825
TI  - Comparison of the safety and immunogenicity of an MF59(r)-adjuvanted with a non
      adjuvanted seasonal influenza vaccine in elderly subjects.
AB  - AIM: Adjuvanted influenza vaccines can overcome the poor antibody response of
      conventional non-adjuvanted vaccines in the elderly. We evaluated the
      immunogenicity, safety and clinical effectiveness of an MF59((r))-adjuvanted
      trivalent influenza vaccine (aTIV) compared with a non-adjuvanted vaccine (TIV)
      in subjects >=65 years old, with or without co-morbidities. METHODS: In 2010
      2011, subjects (N=7082) were randomized to receive one dose of aTIV or TIV. Co
      primary objectives were to assess lot-to-lot consistency of aTIV, non
      inferiority, superiority and immunogenicity 22 days after vaccination. Clinical
      effectiveness, reactogenicity and serious adverse events were monitored up to Day
      366. RESULTS: The immunological equivalence of three lots of aTIV was
      demonstrated. aTIV was not only non-inferior to TIV but also elicited
      significantly higher antibody responses at Day 22 than TIV against all homologous
      and heterologous strains, even in subjects with co-morbidities. Superiority was
      not established. Reactogenicity was higher in the aTIV group, but reactions were
      mild to moderate and transient. CONCLUSIONS: aTIV elicited a significantly higher
      antibody response than TIV, especially against A/H3N2 strains, although
      superiority by pre-defined criteria was not formally met. The study demonstrates
      potential immunological benefits of MF59-adjuvanted influenza vaccines for the
      elderly. This trial was registered with www.clinicaltrials.gov (NCT01162122).

PMID- 25045826
TI  - Generation of an attenuated Salmonella-delivery strains expressing adhesin and
      toxin antigens for progressive atrophic rhinitis, and evaluation of its immune
      responses in a murine model.
AB  - An expression/secretion plasmid containing genes encoding the FimA, CP39, PtfA,
      ToxA and F1P2 antigens associated with porcine pneumonic pasteurellosis and
      progressive atrophic rhinitis (PAR) was constructed and harbored in an attenuated
      Salmonella Typhimurium, which was used as the vaccine candidate. The immune
      responses induced by this delivery strain were investigated in a murine model.
      Each antigen secreted from the delivery strain was confirmed by Western blot
      analysis. Thirty BALB/c mice were divided equally into two groups; group A were
      intranasally inoculated with the mixture of the five delivery strains, and group
      B were inoculated with sterile PBS. In group A, all antigen-specific serum IgG
      were significantly increased compared to those of group B from the 2nd week post
      inoculation (WPI) till the 8th WPI. All antigen-specific mucosal IgA in group A
      were also significantly greater than those of group B. In addition, the
      significant splenic lymphocyte proliferative responses, the elevations of
      CD3(+)CD4(+), CD3(+)CD8(+) and B-cell populations, and the induction of IFN-gamma
      expression in group A were observed. In conclusion, the mixture of five delivery
      strains expressing specific antigen for these diseases was found to be capable of
      inducing significant humoral and cellular immune responses. 

PMID- 25045828
TI  - Cellular Trojan horse based polymer nanoreactors with light-sensitive activity.
AB  - Stimulus-sensitive systems at the nanoscale represent ideal candidates for
      improving therapeutic and diagnostic approaches by producing rapid responses to
      the presence of specific molecules or conditions either by changing properties or
      by acting "on demand". Here we introduce an optimized light-sensitive nanoreactor
      based on encapsulation of a photosensitizer inside polymer vesicles to serve as
      an efficient source of reactive oxygen species (ROS) "on demand". Two types of
      amphiphilic block copolymers, poly(2-methyloxazoline)-block
      poly(dimethylsiloxane)-block-poly(2-methyloxazoline), PMOXA-PDMS-PMOXA, and
      poly(N-vinylpyrrolidone)-block-poly(dimethylsiloxane)-block-poly(N
      vinylpyrrolidone), PNVP-PDMS-PNVP, were used to encapsulate Rose Bengal-bovine
      serum albumin (RB-BSA) inside the cavity of vesicles. The difference of
      copolymers molecular properties (hydrophobic to hydrophilic ratio, different
      chemical nature of the hydrophilic block) influenced the encapsulation ability,
      and uptake by cells, allowing therefore a selection of the most efficient polymer
      system. Nanoreactors were optimized in terms of (i) size, (ii) stability, and
      (iii) encapsulation efficiency based on a combination of light scattering, TEM,
      and UV-vis spectroscopy. By illumination, encapsulated RB-BSA conjugates
      generated in situ ROS, which diffused through the polymer membrane to the
      environment of the vesicles, as proved by electron spin resonance spectroscopy
      (ESR). Optimum illumination conditions were obtained based on the effect of the
      illumination time on the amount of ROS produced in situ by the encapsulated RB
      BSA conjugates. ROS diffusion monitored by ESR was dependent on the molecular
      weight of copolymer that influences the thickness of the polymer membrane. Upon
      uptake into HeLa cells our nontoxic nanoreactors acted as a Trojan horse: they
      produced illumination-controlled ROS in sufficient amounts to induce cell death
      under photodynamic therapy (PDT) conditions. Straightforward production,
      stability, and Trojan horse activity inside cells support our light-sensitive
      nanoreactors for medical applications which require ROS to be generated with
      precise time and space control. 

PMID- 25045827
TI  - Vaccine focusing to cross-subtype HIV-1 gp120 variable loop epitopes.
AB  - We designed synthetic, epitope-focused immunogens that preferentially display
      individual neutralization epitopes targeted by cross-subtype anti-HIV V3 loop
      neutralizing monoclonal antibodies (mAbs). Vaccination of rabbits with these
      immunogens resulted in the elicitation of distinct polyclonal serum Abs that
      exhibit cross-subtype neutralization specificities mimicking the mAbs that guided
      the design. Our results prove the principle that a predictable range of epitope
      specific polyclonal cross-subtype HIV-1 neutralizing Abs can be intentionally
      elicited in mammals by vaccination. The precise boundaries of the epitopes and
      conformational flexibility in the presentation of the epitopes in the immunogen
      appeared to be important for successful elicitation. This work may serve as a
      starting point for translating the activities of human broadly neutralizing anti
      HIV-1 monoclonal antibodies (bNAbs) into matched immunogens that can contribute
      to an efficacious HIV-1 vaccine.

PMID- 25045829
TI  - Methylation of suppressor of cytokine signalling 1 gene promoter is associated
      with acute-on-chronic hepatitis B liver failure.
AB  - Suppressor of cytokine signalling 1 (SOCS1) was demonstrated to play an important
      negative role in fulminant hepatitis and might be involved in acute-on-chronic
      hepatitis B liver failure (ACHBLF). This study was therefore to identify the
      potential role of SOCS1 and its promoter methylation pattern in ACHBLF patients.
      Sixty ACHBLF patients, 60 chronic hepatitis B (CHB) patients and 30 healthy
      controls were investigated in this study. We found that expression of SOCS1 mRNA
      in CHB and ACHBLF patients was significantly higher than that in healthy
      controls. The serum level of IL-6, IFN-gamma and TNF-alpha was significantly
      higher in ACHBLF than CHB. Increased serum level of IL-6, IFN-gamma and TNF-alpha
      was correlated with total bilirubin, ALT, PTA and MELD scores in ACHBLF. The
      degree of methylation of the SOCS1 in ACHBLF patients (35.0%, 21/60) was
      significantly higher than that in CHB patients (16.7%, 10/60). Furthermore,
      methylated group showed lower level of SOCS1, and higher MELD scores and
      mortality rate when compared with unmethylated group of ACHBLF. These results
      suggested that SOCS1 might contribute to immune-related liver damage in ACHBLF,
      and its aberrant methylation may be a key event for the prognosis of ACHBLF. 

PMID- 25045830
TI  - Differentiated NSC-34 cells as an in vitro cell model for VX.
AB  - The US military has placed major emphasis on developing therapeutics against
      nerve agents (NA). Current efforts are hindered by the lack of effective in vitro
      cellular models to aid in the preliminary screening of potential candidate
      drugs/antidotes. The development of an in vitro cellular model to aid in
      discovering new NA therapeutics would be highly beneficial. In this regard, we
      have examined the response of a differentiated hybrid neuronal cell line, NSC-34,
      to the NA VX. VX-induced apoptosis of differentiated NSC-34 cells was measured by
      monitoring the changes in caspase-3 and caspase-9 activity post-exposure.
      Differentiated NSC-34 cells showed an increase in caspase-3 activity in a manner
      dependent on both time (17-23 h post-exposure) and dose (10-100 nM). The maximal
      increase in caspase-3 activity was found to be at 20-h post-exposure. Caspase-9
      activity was also measured in response to VX and was found to be elevated at all
      concentrations (10-100 nM) tested. VX-induced cell death was also observed by
      utilizing annexin V/propidium iodide flow cytometry. Finally, VX-induced caspase
      3 or -9 activities were reduced with the addition of pralidoxime (2-PAM), one of
      the current therapeutics used against NA toxicity, and dizocilpine (MK-801).
      Overall the data presented here show that differentiated NSC-34 cells are
      sensitive to VX-induced cell death and could be a viable in vitro cell model for
      screening NA candidate therapeutics.

PMID- 25045832
TI  - Probiotic-enriched foods and dietary supplement containing SYNBIO positively
      affects bowel habits in healthy adults: an assessment using standard statistical
      analysis and Support Vector Machines.
AB  - A randomised, double-blind, placebo-controlled, parallel group study assessed in
      healthy adults how daily consumption of the probiotic combination SYNBIO(r),
      administered in probiotic-enriched foods or in a dietary supplement, affected
      bowel habits. Primary and secondary outcomes gave the overall assessment of bowel
      well-being, while a Psychological General Well-Being Index compiled by
      participants estimated the health-related quality of life as well as the
      gastrointestinal tolerance determined with the Gastrointestinal Symptom Rating
      Scale. Support Vector Machine models for classification problems were used to
      validate the total outcomes on bowel well-being. SYNBIO(r) consumption improved
      bowel habits of volunteers consuming the probiotic foods or capsules, while the
      same effects were not registered in the control groups. The recovery of probiotic
      bacteria from the faeces of a cohort of 100 subjects for each supplemented group
      showed the persistence of strains in the gastrointestinal tract.

PMID- 25045834
TI  - A review of acute care interventions to improve inpatient pneumococcal
      vaccination.
AB  - OBJECTIVE: To provide a narrative review of the impact of provider-based,
      organizational strategies in acute care settings to improve pneumococcal
      vaccination rates among patients over 65, and 2-64 years with high risk medical
      conditions. METHODS: A search was conducted using MEDLINE, Scopus, CINAHL and Web
      of Science databases for hospital-based, inpatient studies which evaluated
      strategies to improve pneumococcal vaccination rates. Studies published in
      English from 1983 to 2013 were included. Data abstracted was analyzed
      descriptively. RESULTS: A total of 35 studies were included; 15 evaluated
      physician reminders (e.g. chart or paper reminders, pre-printed orders (PPOs),
      computerized reminders, checklists) and 21 standing orders programs (SOPs). The
      most common study design was pre/post, and only 7 studies had a control group.
      Overall, 32 studies showed improvements in the rate of pneumococcal vaccination
      following intervention (19 statistically significant), with reminders showing 29
      74% immunization rate, PPCO 5-42%, and SOPs 3.4-78%. CONCLUSION: Hospital-based
      interventions improve pneumococcal vaccination in older adults and younger
      individuals at risk. Although this review found that more success was observed
      with SOPs the impact on immunization rates in eligible patients varied
      significantly. Thus, high quality, randomized-controlled studies are required to
      determine the effect of each type of institutional immunization strategy.

PMID- 25045833
TI  - Coherent anti-Stokes Raman scattering (CARS) microscopy visualizes pharmaceutical
      tablets during dissolution.
AB  - Traditional pharmaceutical dissolution tests determine the amount of drug
      dissolved over time by measuring drug content in the dissolution medium. This
      method provides little direct information about what is happening on the surface
      of the dissolving tablet. As the tablet surface composition and structure can
      change during dissolution, it is essential to monitor it during dissolution
      testing. In this work coherent anti-Stokes Raman scattering microscopy is used to
      image the surface of tablets during dissolution while UV absorption spectroscopy
      is simultaneously providing inline analysis of dissolved drug concentration for
      tablets containing a 50% mixture of theophylline anhydrate and ethyl cellulose.
      The measurements showed that in situ CARS microscopy is capable of imaging
      selectively theophylline in the presence of ethyl cellulose. Additionally, the
      theophylline anhydrate converted to theophylline monohydrate during dissolution,
      with needle-shaped crystals growing on the tablet surface during dissolution. The
      conversion of theophylline anhydrate to monohydrate, combined with reduced
      exposure of the drug to the flowing dissolution medium resulted in decreased
      dissolution rates. Our results show that in situ CARS microscopy combined with
      inline UV absorption spectroscopy is capable of monitoring pharmaceutical tablet
      dissolution and correlating surface changes with changes in dissolution rate. 

PMID- 25045831
TI  - Living laboratory: whole-genome sequencing as a learning healthcare enterprise.
AB  - With the proliferation of affordable large-scale human genomic data come profound
      and vexing questions about management of such data and their clinical
      uncertainty. These issues challenge the view that genomic research on human
      beings can (or should) be fully segregated from clinical genomics, either
      conceptually or practically. Here, we argue that the sharp distinction between
      clinical care and research is especially problematic in the context of large
      scale genomic sequencing of people with suspected genetic conditions. Core goals
      of both enterprises (e.g. understanding genotype-phenotype relationships;
      generating an evidence base for genomic medicine) are more likely to be realized
      at a population scale if both those ordering and those undergoing sequencing for
      diagnostic reasons are routinely and longitudinally studied. Rather than relying
      on expensive and lengthy randomized clinical trials and meta-analyses, we propose
      leveraging nascent clinical-research hybrid frameworks into a broader, more
      permanent instantiation of exploratory medical sequencing. Such an investment
      could enlighten stakeholders about the real-life challenges posed by whole-genome
      sequencing, such as establishing the clinical actionability of genetic variants,
      returning 'off-target' results to families, developing effective service delivery
      models and monitoring long-term outcomes. 

PMID- 25045835
TI  - Gender differences in the relationship between risk of hypertension and fruit
      intake.
AB  - OBJECTIVE: To investigate the relationship between hypertension and fruit intake
      in an Asian population. METHOD: This study was based on the data from 2007, 2008
      and 2009 Korea National Health and Nutrition Examination Survey. In the final
      analysis, a total of 9791 subjects (men=3819, women=5972) were included. Daily
      energy and nutrient intakes were assessed using 24-h recall. The odds ratios
      (ORs) for hypertension were assessed by using logistic regression and
      multivariable models. RESULTS: A total of 10.6% of individuals were classified as
      having hypertension. Compared with the lowest quintile of fruit intake, the fifth
      quintile showed the lowest likelihood of hypertension (OR 0.73; 95% confidence
      interval [CI], 0.61-0.88) after adjusting for age and gender. For women, the
      likelihood of hypertension in the 2nd, 3rd, 4th and 5th quintiles of fruit intake
      decreased to 0.67 (95% CI, 0.34-1.30), 0.76 (0.56-1.05), 0.90 (0.67-1.22) and
      0.54 (0.38-0.77), respectively, after adjusting for confounding factors (P value
      for trend=0.0011). An inverse association of fruit intake and hypertension was
      shown only in non-obese women. For men and obese women, there was no relationship
      between fruit intake and hypertension. CONCLUSION: Dietary fruit recommendation
      for hypertension should be taken into account together with ethnic background,
      gender as well as the presence of obesity in individuals.

PMID- 25045836
TI  - Self-rated health and mortality in a prospective Chinese elderly cohort study in
      Hong Kong.
AB  - OBJECTIVES: In the West, self-rated health reliably predicts death, but
      conceptualizations of health and cause-composition of mortality may be
      contextually specific. Little is known as to how self-rated health predicts death
      in non-Western settings. METHODS: Multivariable Cox regression analysis was used
      to assess the adjusted associations of age-comparative and self-comparative self
      rated health with death from all- and specific-causes using a population-based
      cohort of 66,820 Chinese (65+years) enrolled from 1998 to 2001 at 18 Elderly
      Health Centers in Hong Kong, and followed until May 31, 2012. RESULTS: During an
      average of 10.9 years follow-up, 19,845 deaths occurred with 6336 from cancer.
      Worse age-comparative self-rated health, compared with better, was positively
      associated with death from all-causes (hazard ratio 1.68, 95% confidence interval
      1.59, 1.77), cardiovascular disease (hazard ratio 1.83, 95% confidence interval
      1.66, 2.02), stroke (hazard ratio 1.93, 95% confidence interval 1.63, 2.29),
      ischemic heart disease (hazard ratio 1.77, 95% confidence interval 1.51, 2.08),
      cancer (hazard ratio 1.17, 95% confidence interval 1.06, 1.30) and respiratory
      disease (hazard ratio 2.25, 95% confidence interval 2.01, 2.52), adjusted for age
      and sex. Self-comparative self-rated health was not associated with higher
      mortality. CONCLUSION: Age-comparative self-rated health predicted death in older
      people from a non-Western setting although the association was less marked than
      in Western settings.

PMID- 25045837
TI  - Reflections on preventive medicine.
AB  - Having thought much about medicine in my career-long effort to understand it and
      the research for its advancement, I have come to views rather different form the
      now-prevailing ones in respect to what preventive medicine is about; what
      epidemiology is in relation to preventive medicine; what distinguishes preventive
      medicine in preventive healthcare at large; the relation of preventive medicine
      to public health; the concept of health promotion; and also the core principles
      of preventive medicine. All of these views I set forth in this article, for the
      readers' critical reflection. 

PMID- 25045838
TI  - Electronic screen use and selected somatic symptoms in 10-12 year old children.
AB  - OBJECTIVE: Screen-based media use by children and adolescents has increased in
      recent years but the consequences of their use are not well understood. The
      objective of this study was to provide a comprehensive examination of the
      relationship between screen-based activities and a selection of single and
      multiple self-reported somatic symptoms in a large sample of 10-12 year old
      children. METHOD: We use data from the population-based 2011 Youth in Iceland
      school survey (N=10,829, response rate: 84.5%, boys: 49.9%) that is conducted
      triennially in 5th-7th grades in all secondary schools in Iceland. Self-reported
      measures of common screen-based activities were hypothesized to predict the odds
      of dizziness, tremors, headaches, stomach aches, and multiple symptoms. RESULTS:
      In general the reported prevalence of symptoms increased with greater number of
      hours reported on screen based activity for boys and girls. This held for all
      individual screen activities as well as the cumulative measure of daily minutes
      spent on screen-based media and prevalence of one or more somatic symptoms.
      CONCLUSIONS: This study confirms previous findings and puts forth additional
      information concerning the relationship between the prevalence of electronic
      screen use and somatic symptoms in 10-12 year old children.

PMID- 25045839
TI  - Barriers to outdoor physical activity and unmet physical activity need in older
      adults.
AB  - OBJECTIVE: To profile participants based on reported outdoor physical activity
      barriers using a data-driven approach, describe the profiles and study their
      association with unmet physical activity need. METHOD: Cross-sectional analyses
      of 848 community-dwelling men and women aged 75-90 living in Central Finland in
      2012. Barriers to outdoor physical activity and unmet physical activity need were
      enquired with a questionnaire. The latent profiles were identified by profiling
      participants into latent groups using a mixture modeling technique on the
      multivariate set of indicators of outdoor physical activity barriers. A path
      model was used to study the associations of the profiles with unmet physical
      activity need. RESULTS: Five barrier profiles were identified. Profile A was
      characterized with minor barriers, profile B with weather barriers, profile C
      with health and weather barriers, profile D with barriers concerning insecurity,
      health and weather; and profile E with mobility and health barriers. The
      participants in the profiles differed in the proportion of individual and
      environmental barriers. The risk for unmet physical activity need was highest
      among people whose severe mobility difficulties restricted their outdoor physical
      activity. CONCLUSION: Outdoor physical activity barriers reflect the imbalance in
      person-environment fit among older people, manifested as unmet physical activity
      need.

PMID- 25045841
TI  - Reflections on conducting evaluations for rural development interventions in
      China.
AB  - An appropriate evaluation methodology is critical in collecting valid data in
      complex development intervention contexts. This paper explores this issue by
      putting forward an appropriate evaluation methodology for development
      interventions in rural China. It draws on the experience of an impact evaluation
      of a sustainable agricultural biodiversity management project conducted in
      Hainan, China in 2010. The authors propose that evaluation be culturally
      responsive and the evaluation design be rooted in the particular cultural context
      where an evaluation is conducted. The appropriate use of the participatory rural
      appraisal (PRA) approach and methods helps generate data that are relevant and
      meaningful for evaluation purposes in rural China. 

PMID- 25045840
TI  - Sex-specific divergence for body size and desiccation-related traits in
      Drosophila hydei from the western Himalayas.
AB  - Sex-specific-differences are a widespread source of genetic variation in various
      Drosophila species. In the present study, we have examined desiccation survival
      in males and females of Drosophila hydei from colder and drier montane conditions
      of the western Himalayas (altitudinal populations; 600-2202 m). In contrast with
      most other studies in drosophilids, D. hydei males exhibited comparatively higher
      desiccation resistance despite smaller body size compared to females.
      Accordingly, we tested the physiological basis of such adaptations in both sexes
      of D. hydei. Body size traits (wing length, wet weight and dry weight) were ~1.2
      fold higher in females than males. However, desiccation resistance was 10 to 13 h
      higher in males than females. These differences matched enhanced storage of
      trehalose content (~1.2 fold), higher hemolymph content (~1.2 fold) and enhanced
      cuticular lipid mass (~1.5 fold) in males than females. Water loss before
      succumbing to death (dehydration tolerance) was much higher in males (~81%) than
      females (~64%). A greater loss of hemolymph water until death under desiccation
      stress was associated with higher desiccation resistance in males. Further, there
      were lacks of differences in the rate of water loss, rate of trehalose
      utilization and rate of hemolymph depletion between the sexes in D. hydei.
      Therefore, sex-specific differences in desiccation resistance of D. hydei were
      independent of body size as well as the exhaustion of metabolite reserves and
      rather were caused by the higher dehydration tolerance as well as higher
      acquisition of hemolymph and trehalose contents.

PMID- 25045842
TI  - An elevated neutrophil-lymphocyte ratio is associated with adverse outcomes
      following single time-point paracetamol (acetaminophen) overdose: a time-course
      analysis.
AB  - BACKGROUND: The innate immune system is profoundly dysregulated in paracetamol
      (acetaminophen)-induced liver injury. The neutrophil-lymphocyte ratio (NLR) is a
      simple bedside index with prognostic value in a number of inflammatory
      conditions. AIM: To evaluate the prognostic accuracy of the NLR in patients with
      significant liver injury following single time-point and staggered paracetamol
      overdoses. PATIENTS AND METHODS: Time-course analysis of 100 single time-point
      and 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Timed
      laboratory samples were correlated with time elapsed after overdose or admission,
      respectively, and the NLR was calculated. RESULTS: A total of 49/100 single time
      point patients developed hepatic encephalopathy (HE). Median NLRs were higher at
      both 72 (P=0.0047) and 96 h after overdose (P=0.0041) in single time-point
      patients who died or were transplanted. Maximum NLR values by 96 h were
      associated with increasing HE grade (P=0.0005). An NLR of more than 16.7 during
      the first 96 h following overdose was independently associated with the
      development of HE [odds ratio 5.65 (95% confidence interval 1.67-19.13),
      P=0.005]. Maximum NLR values by 96 h were strongly associated with the
      requirement for intracranial pressure monitoring (P<0.0001), renal replacement
      therapy (P=0.0002) and inotropic support (P=0.0005). In contrast, in the
      staggered overdose cohort, the NLR was not associated with adverse outcomes or
      death/transplantation either at admission or subsequently. CONCLUSION: The NLR is
      a simple test which is strongly associated with adverse outcomes following single
      time-point, but not staggered, paracetamol overdoses. Future studies should
      assess the value of incorporating the NLR into existing prognostic and triage
      indices of single time-point paracetamol overdose.

PMID- 25045843
TI  - Learning curve for endoscopic submucosal dissection of gastric neoplasms.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is a widely accepted method
      for the treatment of early gastrointestinal neoplasms. OBJECTIVES: To investigate
      the learning curve of ESD performed by a single endoscopist focusing on
      developing the performance of dissection, shortening the procedure time, and
      preventing complications. PATIENTS AND METHODS: Records of 120 consecutive ESD
      procedures performed by a single endoscopist with an ESD knife from December 2007
      to April 2013 were collected. For analysis of the learning curve, total
      procedures were divided into four periods, each comprising 30 sequential ESD
      procedures. Adjusted procedure time (min) was calculated as specimen area
      [pi*long length (mm)*short length (mm)/4]/procedure time. The parameters assessed
      were the en-bloc resection rate, complete resection rate, duration and speed of
      procedure time, and related complications. RESULTS: Procedure times were
      significantly longer with lesions located at the upper third of the stomach and
      with the specimen sizes exceeding 1500 mm. There were significant differences in
      the adjusted overall procedure time from the first to the third quarter (19.9+/
      11.0 vs. 30.3+/-11.8, P=0.01) and to the fourth quarter (19.9+/-11.0 vs. 35.8+/
      15.7, P<0.01), and from the second to the third quarter (21.1+/-8.3 vs. 30.3+/
      11.8, P=0.04) and to the fourth quarter (21.1+/-8.3 vs. 35.8+/-15.7, P<0.01).
      CONCLUSION: ESD for gastric neoplasms can be performed with a steady speed after
      the experience of 60 ESD procedures with proper clinical outcomes. Further
      studies with different endoknives will be required for ESD operators as a
      reference.

PMID- 25045844
TI  - RFT2 is overexpressed in esophageal squamous cell carcinoma and promotes
      tumorigenesis by sustaining cell proliferation and protecting against cell death.
AB  - Human riboflavin transporter 2 (RFT2, also termed as SLC52A3) was recently
      identified as a susceptibility gene to esophageal squamous cell carcinoma (ESCC),
      however, its expression and biologic function has remained unclear in ESCC. In
      this study, we demonstrated that RFT2 was frequently overexpressed in tumor
      samples compared with normal adjacent tissue in ESCC patients. Knockdown of RFT2
      in ESCC cells resulted in decreases of intracellular flavin status, mitochondrial
      membrane potential and cellular ATP levels, and inhibitions of cell
      proliferation, colony formation and anchorage-independent growth. Knockdown of
      RFT2 increased p21 and p27 protein levels, decreased their downstream targets
      cyclin E1 and Cdk2 protein levels and caused pRb hypophosphorylation, leading to
      cell cycle arrest at G1-G1/S. Knockdown of RFT2 also reduced anti-apoptotic
      proteins Bcl-2, Bcl-xl and survivin levels, caused activation of caspase-3 and
      apoptosis. In contrast, ectopic overexpression of RFT2 in ESCC cells promoted
      cell proliferation under restricted conditions (soft agar), conferred resistance
      to cisplatin, and enhanced tumorigenicity in nude mice. These results suggest
      that RFT2 contributes to ESCC tumorigenesis and may serve as a potential
      therapeutic target. 

PMID- 25045845
TI  - The telomere/telomerase binding factor PinX1 regulates paclitaxel sensitivity
      depending on spindle assembly checkpoint in human cervical squamous cell
      carcinomas.
AB  - Paclitaxel is a main ingredient in the combination chemotherapy treatment of
      advanced human cervical squamous cell carcinomas. We investigated the roles and
      underlying molecular mechanisms of PinX1 in cervical squamous cell carcinomas
      (CSCC) cells response to paclitaxel and its clinical significances. The
      expression dynamics of PinX1 was first examined by immunohistochemistry in 122
      advanced CSCC patients treated with cisplatin/paclitaxel chemotherapy. The
      expression of PinX1 was significantly associated with the effects of
      cisplatin/paclitaxel chemotherapy in advanced CSCCs (P<0.05). High expression of
      PinX1 correlated with CSCC's response to cisplatin/paclitaxel chemotherapy, and
      was an independent predictor of shortened survival (P<0.05). A series of in vivo
      and in vitro assays were performed to elucidate the function of PinX1 on CSCC
      cells chemosensitivity to paclitaxel and underlying mechanisms. In CSCC cells,
      the levels of PinX1 were only associated with the cytotoxicity and sensitivity of
      paclitaxel, in which knockdown of PinX1 dramatically enhanced paclitaxel
      cytotoxicity, whereas the reestablishment of PinX1 levels substantially reduced
      the paclitaxel-induced killing effect. In addition, we identified that the
      ability of PinX1 to stabilize the tension between sister kinetochores and
      maintain the spindle assembly checkpoint was the main reason CSCC cells undergo
      apoptosis when treated with paclitaxel, and further studies demonstrated that
      shortened distance between sisters kinetochores by nocodazole confers upon PinX1
      replenished cells a sensitivity to the death inducing paclitaxel effects.
      Furthermore, our study of CSCC cells xenografts in nude mice confirmed the role
      of PinX1 in paclitaxel sensitivity in vivo. Our data reveal that PinX1 could be
      used as a novel predictor for CSCC patient response to paclitaxel, and the role
      of PinX1-mediated paclitaxel sensitivity might represent a new direction for the
      development of a new generation of microtubule drugs. 

PMID- 25045846
TI  - p63-Mediated activation of the beta-catenin/c-Myc signaling pathway stimulates
      esophageal squamous carcinoma cell invasion and metastasis.
AB  - The development of esophageal squamous carcinomas (ESC) results from numerous
      genetic alterations. Our previous study demonstrated that p63 is highly expressed
      in human ESC cells and stimulates their growth; however, the mechanism by which
      p63 regulates ESC cell adhesion and invasion remains unclear. In the present
      study, we further elucidated the underlying molecular mechanisms by which p63
      regulates metastasis in ESC cells. Knockdown of p63 significantly diminished the
      invasion of ESC cell lines TE-8 and TE-12, whereas overexpression of p63
      significantly increased the migration rates of BE3 and OE33 cells. The mRNA and
      protein levels of vimentin, twist, SUSD2, and uPA were significantly decreased in
      p63-knockdown ESC cells, while overexpression of p63 induced an increase in
      vimentin, SUSD2, and uPA. In addition, knockdown of p63 in ESC cells
      significantly reduced levels of beta-catenin and c-Myc, while overexpression of
      p63 increased beta-catenin, but reduced p-beta-catenin level. Therefore, p63
      regulates the migration and invasion of ESC cells through activation of the beta
      catenin/c-Myc pathway. Our results suggest that targeting p63 may constitute a
      potential therapeutic strategy for ESC. 

PMID- 25045847
TI  - Femoral bone marrow aspiration in live mice.
AB  - Serial sampling of the cellular composition of bone marrow (BM) is a routine
      procedure critical to clinical hematology. This protocol describes a detailed
      step-by-step technical procedure for an analogous procedure in live mice which
      allows for serial characterization of cells present in the BM. This procedure
      facilitates studies aimed to detect the presence of exogenously administered
      cells within the BM of mice as would be done in xenograft studies for instance.
      Moreover, this procedure allows for the retrieval and characterization of cells
      enriched in the BM such as hematopoietic stem and progenitor cells (HSPCs)
      without sacrifice of mice. Given that the cellular composition of peripheral
      blood is not necessarily reflective of proportions and types of stem and
      progenitor cells present in the marrow, procedures which provide access to this
      compartment without requiring termination of the mice are very helpful. The use
      of femoral bone marrow aspiration is illustrated here for cytological analysis of
      marrow cells, flow cytometric characterization of the hematopoietic
      stem/progenitor compartment, and culture of sorted HSPCs obtained by femoral BM
      aspiration compared with conventional marrow harvest. 

PMID- 25045848
TI  - A stepwise enteral nutrition algorithm for critically ill children helps achieve
      nutrient delivery goals*.
AB  - OBJECTIVES: To evaluate the impact of implementing an enteral nutrition algorithm
      on achieving optimal enteral nutrition delivery in the PICU. DESIGN: Prospective
      pre/post implementation audit of enteral nutrition practices. SETTING: One 29-bed
      medical/surgical PICU in a freestanding, university-affiliated children's
      hospital. PATIENTS: Consecutive patients admitted to the PICU over two 4-week
      periods pre and post implementation, with a stay of more than 24 hours who
      received enteral nutrition. INTERVENTIONS: Based on the results of our previous
      study, we developed and systematically implemented a stepwise, evidence and
      consensus-based algorithm for initiating, advancing, and maintaining enteral
      nutrition in critically ill children. Three months after implementation, we
      prospectively recorded clinical characteristics, nutrient delivery, enteral
      nutrition interruptions, parenteral nutrition use, and ability to reach energy
      goal in eligible children over a 4-week period. Clinical and nutritional
      variables were compared between the pre and postintervention cohorts. Time to
      achieving energy goal was analyzed using Kaplan-Meier statistical analysis.
      MEASUREMENTS AND MAIN RESULTS: Eighty patients were eligible for this study and
      were compared to a cohort of 80 patients in the preimplementation audit. There
      were no significant differences in median age, gender, need for mechanical
      ventilation, time to initiating enteral nutrition, or use of postpyloric feeding
      between the two cohorts. We recorded a significant decrease in the number of
      avoidable episodes of enteral nutrition interruption (3 vs 51, p < 0.0001) and
      the prevalence and duration of parenteral nutrition dependence in patients with
      avoidable enteral nutrition interruptions in the postintervention cohort. Median
      time to reach energy goal decreased from 4 days to 1 day (p < 0.0001), with a
      higher proportion of patients reaching this goal (99% vs 61%, p = 0.01).
      CONCLUSIONS: The implementation of an enteral nutrition algorithm significantly
      improved enteral nutrition delivery and decreased reliance on parenteral
      nutrition in critically ill children. Energy intake goal was reached earlier in a
      higher proportion of patients.

PMID- 25045849
TI  - Assessment of the infectivity potential of Leishmania infantum, using flow
      cytometry.
AB  - The protozoan parasite Leishmania infantum causes leishmaniases, a sandfly-borne
      disease of humans and dogs, in all countries of the Mediterranean basin. The
      promastigote, infective stage of the parasite, once inoculated to the mammalian
      host by the vector, is ingested by macrophages. Leishmania lives within the
      lysosome of the phagocytic immune cells inactivating the enzymes contained. The
      ability of an isolate to survive within the macrophage and its rate of
      multiplication in this environment is an important factor determining the
      infectivity potential of the isolate and the manifestation of the disease. This
      capacity of the parasite is measured as the percentage of infected cells and the
      mean value of parasites per cell. The infectivity potential, of clinical isolates
      of L. infantum infecting THP-1 cells in vitro, was studied by flow cytometry and
      light microscopy. The percentages of cells in a sample containing a specific
      number of parasites, as recorded by light microscopy, were used in flow cytometry
      to manually gate the mean fluorescence intensity which corresponded to the
      percentage of cells with that number of parasites. The gating obtained, was then
      used as a "standard reference curve" to evaluate results by flow cytometry
      compared to those obtained by light microscopy. The results, of the overall
      percentage of infected cells and the number of parasites per cell in the culture,
      matched in the two methods. So, flow cytometry can be used as a rapid, cost
      effective, easy and reproducible method to study the infectivity potential of
      isolates, either in biological, epidemiological, or clinical tests, particularly
      for the assessment of drug efficiency trials. 

PMID- 25045850
TI  - Brain endothelial cells increase the proliferation of Plasmodium falciparum
      through production of soluble factors.
AB  - We here describe the novel finding that brain endothelial cells in vitro can
      stimulate the growth of Plasmodium falciparum through the production of low
      molecular weight growth factors. By using a conditioned medium approach, we show
      that the brain endothelial cells continued to release these factors over time. If
      this mirrors the in vivo situation, these growth factors potentially would
      provide an advantage, in terms of enhanced growth, for sequestered parasitised
      red blood cells in the brain microvasculature. We observed this phenomenon with
      brain endothelial cells from several sources as well as a second P. falciparum
      strain. The characteristics of the growth factors included: <3 kDa molecular
      weight, heat stable, and in part chloroform soluble. Future efforts should be
      directed at identifying these growth factors, since blocking their production or
      actions might be of benefit for reducing parasite load and, hence, malaria
      pathology.

PMID- 25045851
TI  - Comparison of host cell invasion and proliferation among Neospora caninum
      isolates obtained from oocysts and from clinical cases of naturally infected
      dogs.
AB  - In a previous study we have shown that the in vitro invasion rate (IR) and
      tachyzoite yield (TY) are associated with the virulence phenotypes of Neospora
      caninum isolates of bovine origin. In addition, we recently observed marked
      differences in virulence when canine isolates were compared in a pregnant BALB/c
      mouse model. In this study, we investigated whether invasion and proliferation
      capacities could be used as virulence-related N. caninum phenotypic traits. Of
      the isolates compared in mice, four canine isolates obtained from oocysts (Nc
      Ger2, Nc-Ger3, Nc-Ger-6, Nc-6 Arg) had shown a low-moderate virulence, and two
      further isolates obtained from dogs with neurological signs (Nc-Bahia, Nc-Liv)
      were highly virulent. The IR for each isolate was determined by a plaque assay
      and the counting of immunofluorescence-labeled parasitophorous vacuoles at 3 days
      post-inoculation (p.i.). The TY was determined by the quantification of
      tachyzoites at 56 h p.i. by real-time PCR. Most of the canine isolates showed
      similar IR values under controlled invasion conditions for 4h and 72 h p.i.,
      indicating a limited time period for invasion similar to that observed for bovine
      isolates. The Nc-Ger3, Nc-Bahia, and Nc-Liv isolates showed a significantly
      higher IR and TY than the Nc-Ger2 and Nc-Ger6 isolates (P<0.0001). A correlation
      was found between the IRs and TY (rho>0.885, P<0.033), as well as between the TY
      and both dam morbidity (rho=0.8452, P<0.033) and pup mortality (rho>0.8117,
      P<0.058) in mice. These results demonstrate the importance both the invasive and
      proliferative capacities have on the virulence of canine N. caninum isolates.

PMID- 25045852
TI  - Novel genotypes of Trypanosoma binneyi from wild platypuses (Ornithorhynchus
      anatinus) and identification of a leech as a potential vector.
AB  - Little is known about the prevalence and pathogenesis of trypanosomes in
      Australian monotremes, and few genetic characterisation studies have been
      conducted with these haemoparasites. During the present investigation, molecular
      and microscopic methods were used to screen peripheral blood (n=28) and
      ectoparasites (n=10 adult ticks; n=5 tick nymphs; n=1 leech; and n>500 tick eggs)
      collected from wild Tasmanian platypuses (Ornithorhynchus anatinus), for the
      presence of trypanosomatid-specific DNA and/or trypomastigotes. The genes for the
      small ribosomal subunit RNA (18S rDNA) and glycosomal glyceraldehyde phosphate
      dehydrogenase (gGAPDH) were amplified and sequenced, prior to conducting
      phylogenetic analyses. The detection rate of the parasite-specific 18S rDNA in
      platypus blood was 85.7% (n=24/28), and the leech was also positive at both loci.
      Microscopically, high parasitaemia and the presence of abundant trypomastigotes,
      morphologically consistent with Trypanosoma binneyi Mackerras (1959), were
      observed in the blood films. Phylogenetic analyses at the 18S locus revealed the
      existence of four trypanosomatid-like genotypes, with variable similarity to two
      previously-described genotypes of T. binneyi (range of genetic p-distance: 0.0
      0.5%). For the gGAPDH locus, for which only one T. binneyi sequence is available
      in GenBank, three genotypes closely related T. binneyi were identified (range of
      genetic p-distance: 0.1-0.4%). The leech-derived trypanosome isolate was
      virtually identical (at the two loci studied) to the other parasites sequenced
      from infected platypuses; however, the molecular or morphological identification
      of the leech species was not possible. Although further studies are required, the
      molecular detection of trypanosomes in an aquatic leech removed from a platypus,
      suggests the possibility that these haematophagous hirudineans may be a vector
      for T. binneyi (and closely related genotypes). 

PMID- 25045853
TI  - Demonstration of proteolytic activation of the epithelial sodium channel (ENaC)
      by combining current measurements with detection of cleavage fragments.
AB  - The described methods can be used to investigate the effect of proteases on ion
      channels, receptors, and other plasma membrane proteins heterologously expressed
      in Xenopus laevis oocytes. In combination with site-directed mutagenesis, this
      approach provides a powerful tool to identify functionally relevant cleavage
      sites. Proteolytic activation is a characteristic feature of the amiloride
      sensitive epithelial sodium channel (ENaC). The final activating step involves
      cleavage of the channel's gamma-subunit in a critical region potentially targeted
      by several proteases including chymotrypsin and plasmin. To determine the
      stimulatory effect of these serine proteases on ENaC, the amiloride-sensitive
      whole-cell current (DeltaIami) was measured twice in the same oocyte before and
      after exposure to the protease using the two-electrode voltage-clamp technique.
      In parallel to the electrophysiological experiments, a biotinylation approach was
      used to monitor the appearance of gammaENaC cleavage fragments at the cell
      surface. Using the methods described, it was demonstrated that the time course of
      proteolytic activation of ENaC-mediated whole-cell currents correlates with the
      appearance of a gammaENaC cleavage product at the cell surface. These results
      suggest a causal link between channel cleavage and channel activation. Moreover,
      they confirm the concept that a cleavage event in gammaENaC is required as a
      final step in proteolytic channel activation. The methods described here may well
      be applicable to address similar questions for other types of ion channels or
      membrane proteins. 

PMID- 25045855
TI  - Histological development of the digestive system of the Amazonian pimelodid
      catfish Pseudoplatystoma punctifer.
AB  - The organogenesis of the digestive system was described in the Amazonian
      pimelodid catfish species Pseudoplatystoma punctifer from hatching (3.5 mm total
      length, TL) to 41 days post-fertilization (dpf) (58.1 mm TL) reared at 28 degrees
      C. Newly hatched larvae showed a simple digestive tract, which appeared as a
      straight undifferentiated and unfolded tube lined by a single layer of columnar
      epithelial cells (future enterocytes). During the endogenous feeding period,
      comprised between 20 and 96 h post-fertilization (3.5 to 6.1 mm TL), the larval
      digestive system experienced a fast transformation with the almost complete
      development and differentiation of most of digestive organs (buccopahrynx,
      oesophagus, intestine, liver and exocrine pancreas). Yolk reserves were not
      completely depleted at the onset of exogenous feeding (4 dpf, 6.1 mm TL), and a
      period of mixed nutrition was observed up to 6 to 7 dpf (6.8 to 7.3 mm TL) when
      yolk was definitively exhausted. The stomach was the organ that latest achieved
      its complete differentiation, characterized by the development of abundant
      gastric glands in the fundic stomach between 10 and 15 dpf (10.9 to 15.8 mm TL)
      and the formation of the pyloric sphincter at the junction of the pyloric stomach
      and the anterior intestine at 15 dpf (15.8 mm TL). The above-mentioned
      morphological and histological features observed suggested the achievement of a
      digestive system characteristic of P. punctifer juveniles and adults. The
      ontogeny of the digestive system in P. punctifer followed the same general
      pattern as in most Siluriform species so far, although some species-specific
      differences in the timing of differentiation of several digestive structures were
      noted, which might be related to different reproductive guilds, egg and larval
      size or even different larval rearing practices. According to present findings on
      the histological development of the digestive system in P. punctifer, some
      recommendations regarding the rearing practices of this species are also provided
      in order to improve the actual larval rearing techniques of this fast-growing
      Neotropical catfish species. 

PMID- 25045856
TI  - Size tailoring of aqueous germanium nanoparticle dispersions.
AB  - We demonstrate a practical route to synthesize Ge nanoparticles (NPs) in multi
      gram quantities via the laser pyrolysis of GeH4 gas. The size of the as-produced
      Ge NPs can be precisely controlled in the range of 19.0 to 65.9 nm via a
      subsequent etching procedure using a dilute H2O2 solution. Stable water
      dispersions of Ge NPs yield particles with a Ge/GeO2 core-shell structure,
      however, the oxide shell can easily be removed and passivated by treatment with
      HCl. The feed materials used in this process are readily available and lead to
      non-toxic, water-based dispersions of Ge NPs. The scalability and convenience of
      this procedure make it attractive as a method to obtain Ge NP dispersions for use
      in applications such as optoelectronic devices and biosensors. 

PMID- 25045854
TI  - Vascular wall extracellular matrix proteins and vascular diseases.
AB  - Extracellular matrix proteins form the basic structure of blood vessels. Along
      with providing basic structural support to blood vessels, matrix proteins
      interact with different sets of vascular cells via cell surface integrin or non
      integrin receptors. Such interactions induce vascular cell de novo synthesis of
      new matrix proteins during blood vessel development or remodeling. Under
      pathological conditions, vascular matrix proteins undergo proteolytic processing,
      yielding bioactive fragments to influence vascular wall matrix remodeling.
      Vascular cells also produce alternatively spliced variants that induce vascular
      cell production of different matrix proteins to interrupt matrix homeostasis,
      leading to increased blood vessel stiffness; vascular cell migration,
      proliferation, or death; or vascular wall leakage and rupture. Destruction of
      vascular matrix proteins leads to vascular cell or blood-borne leukocyte
      accumulation, proliferation, and neointima formation within the vascular wall;
      blood vessels prone to uncontrolled enlargement during blood flow diastole;
      tortuous vein development; and neovascularization from existing pathological
      tissue microvessels. Here we summarize discoveries related to blood vessel matrix
      proteins within the past decade from basic and clinical studies in humans and
      animals - from expression to cross-linking, assembly, and degradation under
      physiological and vascular pathological conditions, including atherosclerosis,
      aortic aneurysms, varicose veins, and hypertension.

PMID- 25045857
TI  - A randomized trial comparing vaginal and laparoscopic hysterectomy vs robot
      assisted hysterectomy.
AB  - STUDY OBJECTIVE: To investigate the hospital cost and short-term clinical outcome
      of traditional minimally invasive hysterectomy vs robot-assisted hysterectomy in
      women primarily not considered candidates for vaginal surgery. DESIGN: Randomized
      controlled trial (Canadian Task Force classification I). SETTING: University
      Hospital in Sweden. PATIENTS: One hundred twenty-two women with uterine size <=
      16 gestational weeks scheduled to undergo minimally invasive hysterectomy because
      of benign disease. INTERVENTIONS: Robot-assisted hysterectomy or traditional
      vaginal or laparoscopic minimally invasive hysterectomy. MEASUREMENTS AND MAIN
      RESULTS: All women underwent surgery as randomized. There were no demographic
      differences between the 2 groups. Vaginal hysterectomy was possible in 41% in the
      traditional minimally invasive group, at a mean hospital cost of $4579 compared
      with $7059 for traditional laparoscopic hysterectomy. This was reflected in a
      mean hospital cost of $993 more per robotic-assisted hysterectomy than for
      traditional minimally invasive hysterectomy when the robot was a preexisting
      investment. This hospital cost increased by $1607 when including investments and
      cost of maintenance. A per-protocol subanalysis comparing laparoscopy and
      robotics demonstrated similar hospital cost when the robot was a preexisting
      investment ($7059 vs $7016). Robotic-assisted hysterectomy was associated with
      less blood loss and fewer postoperative complications. CONCLUSION: A similar
      hospital cost can be attained for laparoscopy and robotics when the robot is a
      preexisting investment. From the perspective of hospital costs, robotic-assisted
      hysterectomy is not advantageous for treating benign conditions when a vaginal
      approach is feasible in a high proportion of patients.

PMID- 25045858
TI  - Rapidly Fatal Internal Carotid Artery Mycotic Aneurysm Rupture in a Rheumatoid
      Patient Taking a TNF-alpha Inhibitor: Case Report and Literature Review.
AB  - OBJECT: Tumor necrosis factor (TNF)-alpha inhibitors are effective at treating
      certain inflammatory and autoimmune disorders. They are generally safe; potential
      adverse events include infections (bacterial, fungal, and viral), congestive
      heart failure exacerbations, and the potential for demyelinating diseases and
      possibly certain malignancies. We present the first documented case of fungal
      internal carotid artery (ICA) mycotic aneurysm in a patient being treated with a
      TNF-alpha inhibitor. We also review the literature on infections with TNF-alpha
      inhibition and the management of previously reported fungal ICA mycotic aneurysm
      cases. CASE DESCRIPTION: A 76-year-old woman with rheumatoid arthritis, treated
      with etanercept and methotrexate, presented with a 2-week history of left
      temporal headaches. She was treated empirically for giant cell arteritis (GCA)
      with oral prednisone, which provided no symptom relief. She was subsequently
      hospitalized for a superficial temporal artery biopsy, which was negative for
      GCA. She returned 2 weeks later after experiencing a left thromboembolic ischemic
      stroke. She had an acute neurologic decline, and a head computed tomography scan
      showed diffuse subarachnoid hemorrhage from a ruptured left fusiform paraclinoid
      ICA aneurysm. She was taken emergently for a craniotomy for clip-wrapping of the
      aneurysm, but intraoperative ultrasound revealed poor flow in the left anterior
      cerebral circulation and a complete infarct of the left-sided anterior
      circulation. The family withdrew care and the patient died. Postmortem analysis
      demonstrated fungi consistent with Aspergillus invading the necrotic left ICA.
      CONCLUSIONS: Although fungal mycotic aneurysms of the ICA are rare, their
      incidence may increase with the expanded use of immunosuppressive medications.
      Patients with rheumatoid arthritis who take potent immunosuppression regimens may
      be prime candidates for mycotic aneurysms because they often have two favoring
      conditions: atherosclerosis and immunosuppression. These ICA aneurysms carry a
      high mortality rate, so early diagnosis and aggressive therapy, potentially by
      endovascular trapping/vessel occlusion coupled with long-term antifungal therapy,
      is essential.

PMID- 25045859
TI  - Endoscopic third ventriculostomy for obstructive hydrocephalus due to
      intraventricular hemorrhage.
AB  - BACKGROUND: Although endoscopic third ventriculostomy (ETV) is the first-line
      treatment for obstructive hydrocephalus due to various pathologies, its role in
      hemorrhage-related obstructive hydrocephalus is poorly defined. We report our
      experience with ETV for hemorrhage-related obstructive hydrocephalus, demonstrate
      it feasibility, and discuss potential advantages over more conventional treatment
      modalities. METHODS: We performed a retrospective analysis of 78 consecutive
      patients who underwent ETV in our institution between January 2003 and January
      2011. We identified 17 consecutive patients who underwent ETV for obstructive
      hydrocephalus related to intraventricular hemorrhage (IVH). RESULTS: ETV was
      performed in 9 men and 8 women (mean age: 58 years; range: 42-79). All patients
      had IVH (n = 17), either alone (n = 3) or with intracranial hemorrhage (n = 4) or
      subarachnoid hemorrhage (SAH) (n = 10). Endoscopic clot evacuation was performed
      in seven cases (41%). External ventricular drain (EVD) was avoided in two
      patients. 15 patients had external EVD, and EVD wean was performed on average 5
      days post-ETV. Two patients died in the early postoperative period (< 1 month)
      from the initial cerebral insult. For the 15 surviving patients, the average
      modified Rankin Scale (mRS) at last follow-up (15 months; range: 1-48) was 2.4.
      Thus most surviving patients were independent (mRS < 3). Of those 15 patients,
      one died (malignancy) at last follow-up. Twelve patients (80%) were
      ventriculoperitoneal shunt-free. The three shunt-dependent patients had
      significant SAH (100%). CONCLUSION: ETV with or without endoscopic clot
      evacuation is feasible for patients with hemorrhage-related obstructive
      hydrocephalus. Potential advantages include avoiding or reducing duration of EVD
      placement and preventing ventriculoperitoneal shunt placement. Further large
      prospective randomized trials are needed to evaluate the safety and efficacy of
      ETV with or without clot evacuation for IVH-related obstructive hydrocephalus.

PMID- 25045860
TI  - Management and prognosis of primary cerebral melanocytic tumors. A case report
      and systematic review.
AB  - Primary melanocytic cerebral tumors form a spectrum of different lesions that
      range from benign to extremely malignant, such as an intracranial melanoma. This
      article points out some characteristics of primary melanocytic cerebral tumors
      and discusses their management and prognosis, based on a systematic literature
      review and a case of primary cerebral malignant melanoma.Because the biological
      characteristics of primary melanocytic cerebral tumors remain unclear, it appears
      that total surgical resection of the tumor followed by oncologic treatment is the
      mainstay of the management. The prognosis still depends on the degree of
      malignancy. 

PMID- 25045861
TI  - Thoracic spine localization using preoperative placement of fiducial markers and
      subsequent CT. A technical report.
AB  - STUDY DESIGN: A retrospective case series evaluating the use of fiducial markers
      with subsequent computed tomography (CT) or CT myelography for intraoperative
      localization. OBJECTIVE: To evaluate the safety and utility of preoperative
      fiducial placement, confirmed with CT myelography, for intraoperative
      localization of thoracic spinal levels. SUMMARY OF BACKGROUND DATA: Thoracic
      spine surgery is associated with serious complications, not the least of which is
      the potential for wrong-level surgery. Intraoperative fluoroscopy is often used
      but can be unreliable due to the patient's body habitus and anatomical variation.
      METHODS: Sixteen patients with thoracic spine pathology requiring surgical
      intervention underwent preoperative fiducial placement at the pedicle of the
      level of interest in the interventional radiology suite. CT or CT myelogram was
      then done to evaluate fiducial location relative to the level of pathology.
      Surgical treatment followed at a later date in all patients. RESULTS: All
      patients underwent preoperative fiducial placement and CT or CT myelography,
      which was done on an outpatient basis in 14 of the 16 patients. Intraoperatively,
      fiducial localization was easily and quickly done with intraoperative fluoroscopy
      leading to correct localization of spinal level in all cases. All patients had
      symptomatic improvement following surgery. There were no complications from
      preoperative localization or operative intervention. CONCLUSIONS: Preoperative
      placement of fiducial markers confirmed with a CT or CT myelogram allows for
      reliable and fast intraoperative localization of the spinal level of interest
      with minimal risks and potential complications to the patient. In most cases, a
      noncontrast CT should be sufficient. This should be an equally reliable means of
      localization while further decreasing potential for complications. CT myelography
      should be reserved for pathology that is not evident on noncontrast CT. Accuracy
      of localization is independent of variations in rib number or vertebral
      segmentation. The technique is a safe, reliable, and rapid means of localizing
      spinal level during surgery.

PMID- 25045862
TI  - An evaluation of a zero-heat-flux cutaneous thermometer in cardiac surgical
      patients.
AB  - BACKGROUND: Although core temperature can be measured invasively, there are
      currently no widely available, reliable, noninvasive thermometers for its
      measurement. We thus compared a prototype zero-heat-flux thermometer with
      simultaneous measurements from a pulmonary artery catheter. Specifically, we
      tested the hypothesis that zero-heat-flux temperatures are sufficiently accurate
      for routine clinical use. METHODS: Core temperature was measured from the
      thermistor of a standard pulmonary artery catheter and with a prototype zero-heat
      flux deep-tissue thermometer in 105 patients having nonemergent cardiac surgery.
      Zero-heat-flux probes were positioned on the lateral forehead and lateral neck.
      Skin surface temperature probes were attached to the forehead just adjacent to
      the zero-heat-flux probe. Temperatures were recorded at 1-minute intervals,
      excluding the period of cardiopulmonary bypass, and for the first 4 postoperative
      hours. Zero-heat-flux and pulmonary artery temperatures were compared with bias
      analysis; differences exceeding 0.5 degrees C were considered to be potentially
      clinically important. RESULTS: The mean duration in the operating room was 279 +/
      75 minutes, and the mean cross-clamp time was 118 +/- 50 minutes. All subjects
      were monitored for an additional 4 hours in the intensive care unit. The average
      overall difference between forehead zero-heat-flux and pulmonary artery
      temperatures (i.e., forehead minus pulmonary artery) was -0.23 degrees C (95%
      limits of agreement of +/-0.82); 78% of the differences were <=0.5 degrees C. The
      average intraoperative temperature difference was -0.08 degrees C (95% limits of
      agreement of +/-0.88); 84% of the differences were <=0.5 degrees C. The average
      postoperative difference was -0.32 degrees C (95% limits of agreement of +/
      0.75); 84% of the differences were <=0.5 degrees C. Bias and precision values for
      neck site were similar to the forehead values. Uncorrected forehead skin
      temperature showed an increasing negative bias as core temperature decreased.
      CONCLUSIONS: Core temperature can be noninvasively measured using the zero-heat
      flux method. Bias was small, but precision was slightly worse than our designated
      0.5 degrees C limits compared with measurements from a pulmonary artery catheter.

PMID- 25045863
TI  - Aromatic-hydroxyl interaction of an alpha-aryl ether lignin model-compound on SBA
      15, present at pyrolysis temperatures.
AB  - An aromatic alpha-aryl ether compound (a benzyl phenyl ether analogue) was
      covalently grafted to mesoporous silica SBA-15, to create BPEa-SBA-15. The BPEa
      SBA-15 was subjected to successive heating cycles up to 600  degrees C, with in
      situ monitoring by DRIFTS. It was found that the toluene moiety coordinates to
      SBA-15 surface silanol hydroxyl groups via an aromatic-hydroxyl interaction. This
      interaction is evidenced by a red-shift of the aromatic C-H stretches, as well as
      a red-shift and broadening of the surface hydroxyl O-H stretches, which are
      features characteristic of a hydrogen bond. These features remain present during
      heating until ~400  degrees C whereupon the ether linkage of BPEa-SBA-15 is
      cleaved, accompanied by loss of the toluene moiety. 

PMID- 25045864
TI  - Food reinforcement and parental obesity predict future weight gain in non-obese
      adolescents.
AB  - BACKGROUND: Food reinforcement, the extent to which people are willing to work to
      earn a preferred snack food, and parental obesity are risk factors for weight
      gain, but there is no research comparing the predictive effects of these factors
      for adolescent weight gain. METHODS: 130 non-obese adolescents (M age=15.2 +/-
      1.0; M BMI=20.7 +/- 2.0; M zBMI=0.16 +/- 0.64) at differential risk for weight
      gain based on parental obesity completed baseline food and money reinforcement
      tasks, and provided zBMI data over a 2-year follow-up. RESULTS: The number of
      obese (BMI >= 30) parents (p=0.007) and high food reinforcement (p=0.046) were
      both significant independent predictors of greater zBMI increases, controlling
      for age, sex, parent education and minority status. Having no obese parents or
      being low or average in food reinforcement was associated with reductions in
      zBMI, but those high in food reinforcement showed larger zBMI increases (0.102)
      than having one obese parent (0.025) but less than having two obese parents
      (0.177). DISCUSSION: Food reinforcement and parental obesity independently
      predict future weight gain among adolescents. It might be fruitful for obesity
      prevention programs to target both high risk groups.

PMID- 25045865
TI  - Eating like you are overweight: the effect of overweight models on food intake in
      a remote confederate study.
AB  - There is consistent evidence that people model the eating behaviour of others.
      The extent to which people model the amount of food consumed by other people of
      different weight statuses has received less attention. Here we tested the effect
      on food consumption of exposing female participants to information about the food
      consumption of either normal/healthy weight or overweight individuals. Eighty
      female participants took part in a between-subjects experiment, in which we used
      a remote-confederate design and manipulated whether participants saw intake
      information about normal/healthy weight or overweight previous participants
      (remote confederates). Regardless of the weight-status of the remote
      confederates, participants ate more food when they believed that previous
      participants had eaten a large amount of food, in comparison with when they
      believed previous participants had eaten a smaller amount of food. These findings
      indicate that women may model the food intake of other women, even when they
      believe they are of a different weight status to themselves. 

PMID- 25045866
TI  - A saponification-triggered gelation of ester-based Zn(II) complex through
      conformational transformations.
AB  - Novel saponification-triggered gelation in an ester-based bis-salen Zn(II)
      complex (1) is described. Strategic structural modifications induced by NaOH in 1
      tune the dipolar-/pi-interactions leading to J-aggregation and the creation of an
      inorganic gel material (IGM), which has been established by photophysical, DFT
      and rheological studies.

PMID- 25045867
TI  - Overcoming limitations in diffusion-weighted MRI of breast by spatio-temporal
      encoding.
AB  - PURPOSE: Evaluating the usefulness of diffusion-weighted spatio-temporal encoding
      (SPEN) methods to provide quantitative apparent diffusion coefficient (ADC)-based
      characterizations of healthy and malignant human breast tissues, in comparison
      with results obtained using techniques based on spin-echo echo planar imaging (SE
      EPI). METHODS: Twelve healthy volunteers and six breast cancer patients were
      scanned at 3T using scanner-supplied diffusion-weighted imaging EPI sequences, as
      well as two fully refocused SPEN variants programmed in-house. Suitable codes
      were written to process the data, including calculations of the actual b-values
      and retrieval of the ADC maps. RESULTS: Systematically better images were
      afforded by the SPEN scans, with negligible geometrical distortions and markedly
      weaker ghosting artifacts arising from either fat tissues or from strongly
      emitting areas such as cysts. SPEN-derived images provided improved
      characterizations of the fibroglandular tissues and of the lesions' contours.
      When translated into the calculation of the ADC maps, there were no significant
      differences between the mean ADCs derived from SPEN and SE-EPI: if reliable
      images were available, both techniques showed that ADCs decreased by nearly two
      fold in the malignant lesion areas. CONCLUSION: SPEN-based sequences yielded
      diffusion-weighted breast images with minimal artifacts and distortions, enabling
      the calculation of improved ADC maps and the identification of decreased ADCs in
      malignant regions.

PMID- 25045868
TI  - Writing well: lowering the barriers to success.

PMID- 25045869
TI  - cASCading specks.

PMID- 25045870
TI  - Peroxisomal MAVS activates IRF1-mediated IFN-lambda production.

PMID- 25045871
TI  - Enhancing the understanding of asthma.

PMID- 25045872
TI  - An antitumor boost to TH9 cells.

PMID- 25045880
TI  - Probing treatment response of glutaminolytic prostate cancer cells to natural
      drugs with hyperpolarized [5-(13) C]glutamine.
AB  - PURPOSE: The correlation between glutamine metabolism and oncogene expression in
      cancers has led to a renewed interest in the role of glutamine in cancer cell
      survival. Hyperpolarized [5-(13) C]glutamine is evaluated as a potential
      biomarker for noninvasive metabolic measurements of drug response in prostate
      cancer cells. METHODS: Hyperpolarized [5-(13) C]glutamine is used to measure
      glutamine metabolism in two prostate cancer cell lines (PC3 and DU145) before and
      after treatment with the two natural anticancer drugs resveratrol and
      sulforaphane. An invasive biochemical assay simulating the hyperpolarized
      experiment is used to independently quantify glutamine metabolism. RESULTS:
      Glutamine metabolism is found to be 4 times higher in the more glutaminolytic
      DU145 cells compared with PC3 cells under proliferating growth conditions by
      using hyperpolarized [5-(13) C]glutamine as a noninvasive probe. A significant
      decrease in glutamine metabolism occurs upon apoptotic response to treatment with
      resveratrol and sulforaphane. CONCLUSION: Hyperpolarized NMR using [5-(13)
      C]glutamine as a probe permits the noninvasive observation of glutaminolysis in
      different cell lines and under different treatment conditions. Hyperpolarized [5
      (13) C]glutamine metabolism thus is a promising biomarker for the noninvasive
      detection of tumor response to treatment, as it directly monitors one of the
      hallmarks in cancer metabolism - glutaminolysis - in living cells.

PMID- 25045881
TI  - Colorectal liver metastases with a disrupted circadian rhythm phase shift the
      peripheral clock in liver and kidney.
AB  - Circadian clock genes regulate 10-15% of the transcriptome, and might function as
      tumor suppressor genes. Relatively little is known about the circadian clock in
      tumors and its effect on surrounding healthy tissues. Therefore, we compared the
      24-hr expression levels of key circadian clock genes in liver and kidney of
      healthy control mice with those of mice bearing C26 colorectal tumor metastases
      in the liver. Metastases were induced by injection of C26 colorectal carcinoma
      cells into the spleen. Subsequently, tumor, liver and kidney tissue was collected
      around the clock to compare circadian rhythmicity. Expression levels of five
      clock genes (Rev-Erbalpha, Per1, Per2, Bmal1 and Cry1) and three clock-controlled
      genes (CCGs; Dbp, p21 and Wee1) were determined by qRT-PCR. Liver and kidney
      tissue of healthy control mice showed normal 24-hr oscillations of all clock
      genes and CCGs, consistent with normal circadian rhythmicity. In colorectal liver
      metastases, however, 24-hr oscillations were completely absent for all clock
      genes and CCGs except Cry1. Liver and kidney tissue of tumor-bearing mice showed
      a shift in clock periodicity relative to control mice. In the liver we observed a
      phase advance, whereas in the kidney the phase was delayed. These data show that
      hepatic metastases of C26 colon carcinoma with a disrupted circadian rhythm phase
      shift liver and kidney tissue clocks, which strongly suggests a systemic effect
      on peripheral clocks. The possibility that tumors may modify peripheral clocks to
      escape from ordinary circadian rhythms and in this way contribute to fatigue and
      sleep disorders in cancer patients is discussed. 

PMID- 25045879
TI  - Type I and type II Fc receptors regulate innate and adaptive immunity.
AB  - Antibodies produced in response to a foreign antigen are characterized by
      polyclonality, not only in the diverse epitopes to which their variable domains
      bind but also in the various effector molecules to which their constant regions
      (Fc domains) engage. Thus, the antibody's Fc domain mediates diverse effector
      activities by engaging two distinct classes of Fc receptors (type I and type II)
      on the basis of the two dominant conformational states that the Fc domain may
      adopt. These conformational states are regulated by the differences among
      antibody subclasses in their amino acid sequence and by the complex, biantennary
      Fc-associated N-linked glycan. Here we discuss the diverse downstream
      proinflammatory, anti-inflammatory and immunomodulatory consequences of the
      engagement of type I and type II Fc receptors in the context of infectious,
      autoimmune, and neoplastic disorders. 

PMID- 25045882
TI  - Reconstructive surgery for females with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency: a review from the Prince of Wales Hospital.
AB  - OBJECTIVES: To present the results of feminising genitoplasty done in female
      patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
      DESIGN: Case series. SETTING: A tertiary referral centre in Hong Kong. PATIENTS:
      Female patients with congenital adrenal hyperplasia undergoing corrective surgery
      for virilisation between 1993 and 2012. MAIN OUTCOME MEASURES: The operative
      result was judged with a scoring system (1-3) for four areas: appearance of
      clitoris, labia and vagina, plus requirement for revision surgery. RESULTS: A
      total of 23 female patients with congenital adrenal hyperplasia with a median age
      of 17.5 (range, 1.5-33.8) years were identified. Of these individuals, 17
      presented in the neonatal period and early infancy, of which four had an
      additional salt-losing crisis. Six patients-including four migrants from mainland
      China-were late presenters at a median age of 2 (range, 0.5-14) years. Twenty-two
      patients had corrective surgery at a median age of 2 (range, 1-14) years.
      Clitoral reduction was performed in all, and further surgery in 21 patients. The
      additional surgery was flap vaginoplasty in 10 patients, a modified Passerini
      procedure in six, and a labial reconstruction in five; one patient with prominent
      clitoris was for observation only. Minor revision surgery (eg mucosal trimming)
      was required in three patients; a revision vaginoplasty was done in one
      individual. Of the 23 patients, 18 (78%) with a median age of 20 (range, 9.3
      33.8) years participated in the outcome evaluation: a 'good' outcome (4 points)
      was seen in 12 patients and a 'satisfactory' (5-9 points) result in five
      patients. CONCLUSIONS: Nearly three quarters of our cohort (n=17) presented with
      classic virilising form of 21-hydroxylase deficiency. Only four (25%) patients
      experienced a salt-losing crisis. Female gender assignment at birth was
      maintained for all individuals in this group. 'Good' and 'satisfactory' outcomes
      of surgery were reported in nearly all participants.

PMID- 25045883
TI  - Paediatric vesicoureteric reflux imaging: where are we? Novel ultrasound-based
      voiding urosonography.
AB  - Vesicoureteric reflux is an important association of paediatric urinary tract
      infection. Fluoroscopic micturating cystourethrography and radionuclide
      cystography have been employed for detecting and grading vesicoureteric reflux.
      However, both modalities involve ionising radiation, which can pose significant
      radiation risk to growing children. They also have a lower detection rate due to
      intermittent fluoroscopic technique in micturating cystourethrography, and lower
      spatial resolution in radionuclide cystography. Therefore, newer radiation-free
      ultrasound-based contrast-enhanced voiding urosonography has been developed in
      Europe for 15 years. This article aimed to summarise the current literature and
      discuss the first local pilot study in our institution on detection of
      vesicoureteric reflux by contrast-enhanced voiding urosonography. Contrast
      enhanced voiding urosonography is a valid alternative to micturating
      cystourethrography in assessing vesicoureteric reflux, based on its superior
      diagnostic performance, reliability, safety, feasibility, and radiation safety
      for children. Therefore, it should be incorporated in the guideline for
      investigating paediatric urinary tract infection. 

PMID- 25045884
TI  - Helicobacter pylori infection and skin disorders.
AB  - Helicobacter pylori is a Gram-negative bacterium that has been linked to peptic
      ulcer disease, gastric lymphoma, and gastric carcinoma. Apart from its well
      demonstrated role in gastroduodenal diseases, some authors have suggested a
      potential role of Helicobacter pylori infection in several extra-intestinal
      pathologies including haematological, cardiovascular, neurological, metabolic,
      autoimmune, and dermatological diseases. Some studies suggest an association
      between Helicobacter pylori infection and skin diseases such as chronic
      idiopathic urticaria and rosacea. There have also been few case reports
      documenting association between Helicobacter pylori and psoriasis vulgaris,
      Behcet's disease, alopecia areata, Henoch-Schonlein purpura, and Sweet's
      syndrome. However, more systematic studies are required to clarify the proposed
      association between Helicobacter pylori and skin diseases; most of the studies do
      not show relevant relationships of these diseases with Helicobacter pylori
      infections. This review discusses skin diseases that are believed to be
      associated with Helicobacter pylori. 

PMID- 25045885
TI  - Optimization of b-value distribution for four mathematical models of prostate
      cancer diffusion-weighted imaging using b values up to 2000 s/mm(2): simulation
      and repeatability study.
AB  - PURPOSE: To find optimal b-value distributions for monoexponential, stretched
      exponential, kurtosis, and biexponential models of prostate cancer (PCa)
      diffusion-weighted imaging (DWI) using simulations and repeated DWI examinations.
      METHODS: Simulations aiming to minimize estimation accuracy error were performed.
      Ten PCa patients underwent in total four repeated 3-tesla DWI examinations using
      12 equally spaced b values (0-2000 s/mm(2) ). Normalized mean signal intensities
      of regions-of-interest placed in normal tissue and PCa were fitted. In total, 210
      different b-value combinations consisting of six b values, 0 and 100 s/mm(2)
      included in every b-value distribution, were evaluated in terms of accuracy and
      repeatability. RESULTS: The simulations and in vivo DWI data suggest the optimal
      b-value distribution for the monoexponential model consists of four to five
      equally distributed b values in the range of 0 to 1200 s/mm(2) . The parameters
      of the stretched exponential and kurtosis models are best estimated using five to
      seven b values in the ranges of 300 to 700 and close to 2000 s/mm(2) , in
      addition to low b value. B-value distribution consisting of eight to 10 b values
      in the ranges of 0 to 100, 800 to 1200, and 1800 to 2000 s/mm(2) is the preferred
      method for estimation of the biexponential model parameters of PCa DWI.
      CONCLUSION: The optimized b-value distributions demonstrated improved estimation
      accuracy and repeatability of DWI signal decay-derived parameters.

PMID- 25045886
TI  - Whole-organ tissue engineering: decellularization and recellularization of three
      dimensional matrix liver scaffolds.
AB  - To report the results of whole liver decellularization by two different methods.
      To present the results of grafting rat and sheep decellularized liver matrix
      (DLM) into the normal rat liver and compare natural cell seeding process in
      homo/xenograft of DLM. To compare the results of in vitro whole liver
      recellularization with rats' neonatal green fluorescent protein (GFP)-positive
      hepatic cells with outcomes of in vivo recellularization process. Whole liver of
      8 rats and 4 sheep were resected and cannulated via the hepatic vein and perfused
      with sodium dodecyl sulfate (SDS) or Triton + SDS. Several examinations were
      performed to compare the efficacy of these two decellularization procedures. In
      vivo recellularization of sheep and rat DLMs was performed following
      transplantation of multiple pieces of both scaffolds in the subhepatic area of
      four rats. To compare the efficacy of different scaffolds in autologous cell
      seeding, biopsies of homograft and xenograft were assessed 8 weeks
      postoperatively. Whole DLMs of 4 rats were also recellularized in vitro by
      perfusion of rat's fetal GFP-positive hepatic cells with pulsatile bioreactor.
      Histological evaluation and enzymatic assay were performed for both in vivo and
      in vitro recellularized samples. The results of this study demonstrated that the
      triton method was a promising decellularization approach for preserving the three
      dimensional structure of liver. In vitro recellularized DLMs were more similar to
      natural ones compared with in vivo recellularized livers. However, homografts
      showed better characteristics with more organized structure compared with
      xenografts. In vitro recellularization of liver scaffolds with autologous cells
      represents an attractive prospective for regeneration of liver as one of the most
      compound organs. In vivo cell seeding on the scaffold of the same species may
      have more satisfactory outcomes when compared with the results of
      xenotransplantation. This study theoretically may pave the road for in situ liver
      regeneration probably by implantation of homologous DLM or in vitro
      recellularized scaffolds into the diseased host liver.

PMID- 25045887
TI  - Human neutrophil flow chamber adhesion assay.
AB  - Neutrophil firm adhesion to endothelial cells plays a critical role in
      inflammation in both health and disease. The process of neutrophil firm adhesion
      involves many different adhesion molecules including members of the beta2
      integrin family and their counter-receptors of the ICAM family. Recently,
      naturally occurring genetic variants in both beta2 integrins and ICAMs are
      reported to be associated with autoimmune disease. Thus, the quantitative
      adhesive capacity of neutrophils from individuals with varying allelic forms of
      these adhesion molecules is important to study in relation to mechanisms
      underlying development of autoimmunity. Adhesion studies in flow chamber systems
      can create an environment with fluid shear stress similar to that observed in the
      blood vessel environment in vivo. Here, we present a method using a flow chamber
      assay system to study the quantitative adhesive properties of human peripheral
      blood neutrophils to human umbilical vein endothelial cell (HUVEC) and to
      purified ligand substrates. With this method, the neutrophil adhesive capacities
      from donors with different allelic variants in adhesion receptors can be assessed
      and compared. This method can also be modified to assess adhesion of other
      primary cell types or cell lines. 

PMID- 25045888
TI  - Two new iridoids from Verbena officinalis L.
AB  - Two new iridoids, 3-(5-(methoxycarbonyl)-2-oxo-2H-pyran-3-yl)butanoic acid, named
      verbeofflin I (1), and 7-hydroxydehydrohastatoside (2), were isolated from the
      aerial part of Verbena officinalis L, along with three known iridoids, verbenalin
      (3), 3,4-dihydroverbenalin (4), hastatoside (5) by means of various column
      chromatography steps. The structures of these compounds were elucidated through
      analysis of their spectroscopic data obtained using 1D and 2D NMR and MS
      techniques. Verbeofflin I (1) is the new class of secoiridoid in the family
      Verbenaceae. 

PMID- 25045889
TI  - Antioxidant, antimicrobial and phytochemical variations in thirteen Moringa
      oleifera Lam. cultivars.
AB  - A study was undertaken to assess variation in antioxidant, antimicrobial and
      phytochemical properties of thirteen Moringa oleifera cultivars obtained from
      different locations across the globe. Standard antioxidant methods including the
      DPPH scavenging, ferric reducing power (FRAP) and beta-carotene-linoleic acid
      model were used to evaluate the activity. Variation in the antioxidant activity
      was observed, with TOT4951 from Thailand being the most active, with activity
      five times higher than that of ascorbic acid (reference compound). A different
      trend was observed for the activity in the FRAP and beta-carotene-linoleic acid
      assays. Antimicrobial activity was tested against Gram-positive (Staphylococcus
      aureus) and Gram-negative (Klebsiella pneumoniae) strains using the microdilution
      method. Acetone extracts of all cultivars exhibited good antibacterial activity
      against K. pneumoniae (MIC values of 0.78 mg/mL). The remaining extracts
      exhibited weak activity against the two microorganisms. For the antifungal
      activity, all the extracts exhibited low activity. Variations were observed in
      the total phenolic and flavonoid contents. Cultivars TOT5169 (Thailand) and SH
      (South Africa) exhibited highest amounts of total phenolic compounds while
      TOT5028 (Thailand) exhibited the lowest amounts of five times lower than the
      highest. The information offer an understanding on variations between cultivars
      from different geographical locations and is important in the search for
      antioxidant supplementation and anti-ageing products. 

PMID- 25045890
TI  - Thioctic acid derivatives as building blocks to incorporate DNA oligonucleotides
      onto gold nanoparticles.
AB  - Oligonucleotide gold nanoparticle conjugates are being used as diagnostic tools
      and gene silencing experiments. Thiol-chemistry is mostly used to functionalize
      gold nanoparticles with oligonucleotides and to incorporate DNA or RNA molecules
      onto gold surfaces. However, the stability of such nucleic acid-gold nanoparticle
      conjugates in certain conditions may be a limitation due to premature break of
      the thiol-gold bonds followed by aggregation processes. Here, we describe a
      straightforward synthesis of oligonucleotides carrying thioctic acid moiety based
      on the use of several thioctic acid-L-threoninol derivatives containing different
      spacers, including triglycine, short polyethyleneglycol, or aliphatic spacers.
      The novel thioctic-oligonucleotides were used for the functionalization of gold
      nanoparticles and the surface coverage and stability of the resulting thioctic
      oligonucleotide gold nanoparticles were assessed. In all cases gold nanoparticles
      functionalized with thioctic-oligonucleotides had higher loadings and higher
      stability in the presence of thiols than gold nanoparticles prepared with
      commercially available thiol-oligonucleotides. Furthermore, the thioctic
      derivative carrying the triglycine linker is sensitive to cathepsin B present in
      endosomes. In this way this derivative may be interesting for the cellular
      delivery of therapeutic oligonucleotides as these results provides the basis for
      a potential endosomal escape. 

PMID- 25045891
TI  - Mistaken identity: clarification of Rubus coreanus Miquel (Bokbunja).
AB  - In the U.S., there has been a recent surge in Korean black raspberry products
      available and in the number of reports about this species appearing in the
      scientific literature. Despite this, the majority of products sold and the work
      carried out has been on Rubus occidentalis L., not R. coreanus Miquel. The
      importance of accurate recognition of all starting material is multiplied for
      research downstream, including genetics/genomics, plant breeding, phenolic
      identification, food processing improvements and pharmacokinetic investigations.
      An overview of distinguishing characteristics separating R. coreanus from R.
      occidentalis will be presented. Research conducted on correctly identified fruit
      will also be summarized to aid future studies that might showcase the unique
      qualities that bokbunja can offer. 

PMID- 25045892
TI  - Reduction of adhesion molecule production and alteration of eNOS and endothelin-1
      mRNA expression in endothelium by Euphorbia hirta L. through its beneficial beta
      amyrin molecule.
AB  - The inflammatory reaction in large blood vessels involves up-regulation of
      vascular adhesion molecules such as endothelial cell selectin (E-selectin),
      soluble vascular cell adhesion molecule (sVCAM)-1, and soluble intercellular
      adhesion molecule (sICAM)-1. These vascular dysfunctions are associated with the
      development of atherosclerosis. beta-Amyrin, an active component of Euphorbia
      hirta L., has potent anti-inflammatory effects. So far, its preventive effects
      against the expression of inflammatory mediator-induced adhesion molecules have
      not been investigated. Endothelial cells (SVEC4-10 cell line) were treated with
      50% RAW conditioned media (i.e., normal SVEC4-10 culture media contains 50% of
      lipopolysaccharide-activated macrophage culture media) without or with beta
      amyrin (0.6 and 0.3 uM). The production levels of E-selectin, sICAM-1, and sVCAM
      1 in the SVEC4-10 cells were measured with ELISA assay kits. Under the same
      treatment conditions, expression of endothelin (ET)-1 and endothelial type of NO
      synthase (eNOS) mRNA were analyzed by RT-PCR and agarose gel. With beta-amyrin,
      the 50% RAW conditioned media-induced E-selectin, sICAM-1, and sVCAM-1 levels as
      well as ET-1 gene expression were all suppressed. beta-Amyrin treatment also
      restored the 50% RAW conditioned media-suppressed eNOS mRNA expression. These
      data indicate that beta-amyrin is potentially useful in preventing chronic
      inflammation-related vascular diseases. 

PMID- 25045893
TI  - Hologram QSAR studies of antiprotozoal activities of sesquiterpene lactones.
AB  - Infectious diseases such as trypanosomiasis and leishmaniasis are considered
      neglected tropical diseases due the lack for many years of research and
      development into new drug treatments besides the high incidence of mortality and
      the lack of current safe and effective drug therapies. Natural products such as
      sesquiterpene lactones have shown activity against T. brucei and L. donovani, the
      parasites responsible for these neglected diseases. To evaluate structure
      activity relationships, HQSAR models were constructed to relate a series of 40
      sesquiterpene lactones (STLs) with activity against T. brucei, T. cruzi, L.
      donovani and P. falciparum and also with their cytotoxicity. All constructed
      models showed good internal (leave-one-out q2 values ranging from 0.637 to 0.775)
      and external validation coefficients (r2test values ranging from 0.653 to 0.944).
      From HQSAR contribution maps, several differences between the most and least
      potent compounds were found. The fragment contribution of PLS-generated models
      confirmed the results of previous QSAR studies that the presence of alpha,beta
      unsatured carbonyl groups is fundamental to biological activity. QSAR models for
      the activity of these compounds against T. cruzi, L. donovani and P. falciparum
      are reported here for the first time. The constructed HQSAR models are suitable
      to predict the activity of untested STLs. 

PMID- 25045894
TI  - Isolation and characterization of an alpha-glucosidase inhibitor from Musa spp.
      (Baxijiao) flowers.
AB  - The use of alpha-glucosidase inhibitors is considered to be an effective strategy
      in the treatment of diabetes. Using a bioassay-guided fractionation technique,
      five Bacillus stearothermophilus alpha-glucosidase inhibitors were isolated from
      the flowers of Musa spp. (Baxijiao). Using NMR spectroscopy analysis they were
      identified as vanillic acid (1), ferulic acid (2), beta-sitosterol (3),
      daucosterol (4) and 9-(4'-hydroxyphenyl)-2-methoxyphenalen-1-one (5). The half
      maximal inhibitory concentration (IC50) values of compounds 1-5 were 2004.58,
      1258.35, 283.67, 247.35 and 3.86 mg/L, respectively. Compared to a known alpha
      glucosidase inhibitor (acarbose, IC50=999.31 mg/L), compounds 3, 4 and 5 showed a
      strong alpha-glucosidase inhibitory effect. A Lineweaver-Burk plot indicated that
      compound 5 is a mixed-competitive inhibitor, while compounds 3 and 4 are
      competitive inhibitors. The inhibition constants (Ki) of compounds 3, 4 and 5
      were 20.09, 2.34 and 4.40 mg/L, respectively. Taken together, these data show
      that the compounds 3, 4 and 5 are potent alpha-glucosidase inhibitors.

PMID- 25045895
TI  - Quantifying single microvessel permeability in isolated blood-perfused rat lung
      preparation.
AB  - The isolated blood-perfused lung preparation is widely used to visualize and
      define signaling in single microvessels. By coupling this preparation with real
      time imaging, it becomes feasible to determine permeability changes in individual
      pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse
      them with autologous blood. Then, we outline steps to infuse fluorophores or
      agents via a microcatheter into a small lung region. Using these procedures
      described, we determined permeability increases in rat lung microvessels in
      response to infusions of bacterial lipopolysaccharide. The data revealed that
      lipopolysaccharide increased fluid leak across both venular and capillary
      microvessel segments. Thus, this method makes it possible to compare permeability
      responses among vascular segments and thus, define any heterogeneity in the
      response. While commonly used methods to define lung permeability require
      postprocessing of lung tissue samples, the use of real time imaging obviates this
      requirement as evident from the present method. Thus, the isolated lung
      preparation combined with real time imaging offers several advantages over
      traditional methods to determine lung microvascular permeability, yet is a
      straightforward method to develop and implement.

PMID- 25045896
TI  - Steroids for treatment of sudden sensorineural hearing loss: a meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: To systematically review the available evidence regarding steroid
      treatment for sudden sensorineural hearing loss (SSHL) and to update prior
      analyses when possible. DATA SOURCES: OVID Medline. REVIEW METHODS: An electronic
      database search (OVID Medline) was performed with the objective of identifying
      all randomized controlled trials examining the use of steroids for the treatment
      of SSHL. The search was limited to English-language publications between January
      1980 and June 2013. Reference lists were examined for additional articles.
      RESULTS: A total of 15 articles including 1,166 subjects were included in three
      separate analyses. Three articles (181 subjects) were included in the steroid
      versus placebo analysis, which resulted in an odds ratio of 1.52 (95% confidence
      interval [CI]: 0.83-2.77). Six articles (702 subjects) were included in the
      systemic versus intratympanic steroids analysis, which resulted in an odds ratio
      of 1.14 (95% CI: 0.82-1.59). Six articles (283 subjects) were included in the
      salvage treatment analysis, which resulted in an odds ratio of 6.04 (95% CI: 3.26
      11.2). CONCLUSIONS: A meta-analysis of randomized controlled trials does not
      support the use of steroids over placebo in this condition, a finding consistent
      with previous analyses. Although systemic or intratympanic steroid administration
      does not have a significant treatment effect, steroids for salvage treatment of
      patients failing traditional therapy appear to have an effect. However, this
      result should be interpreted with caution given the poor quality of component
      trials. Implications for clinical practice and future trial design are discussed.

PMID- 25045897
TI  - Optimized radiofrequency coil setup for MR examination of living isolated rat
      hearts in a horizontal 9.4T magnet.
AB  - PURPOSE: (i) To optimize an MR-compatible organ perfusion setup for the
      nondestructive investigation of isolated rat hearts by placing the radiofrequency
      (RF) coil inside the perfusion chamber; (ii) to characterize the benefit of this
      system for diffusion tensor imaging and proton ((1) H-) MR spectroscopy. METHODS:
      Coil quality assessment was conducted both on the bench, and in the magnet. The
      benefit of the new RF-coil was quantified by measuring signal-to-noise ratio
      (SNR), accuracy, and precision of diffusion tensor imaging/error in metabolite
      amplitude estimation, and compared to an RF-coil placed externally to the
      perfusion chamber. RESULTS: The new design provided a 59% gain in signal-to-noise
      ratio on a fixed rat heart compared to using an external resonator, which found
      reflection in an improvement of living heart data quality, compared to previous
      external resonator studies. This resulted in 14-29% improvement in accuracy and
      precision of diffusion tensor imaging. The Cramer-Rao lower bounds for metabolite
      amplitude estimations were up to 5-fold smaller. CONCLUSION: Optimization of MR
      compatible perfusion equipment advances the study of rat hearts with improved
      signal-to-noise ratio performance, and thus improved accuracy/precision.

PMID- 25045898
TI  - Broader liver sharing: the time has come.

PMID- 25045901
TI  - Limits on action priming by pictures of objects.
AB  - When does looking at an object prime actions associated with using it, and what
      aspects of those actions are primed? We examined whether viewing manmade objects
      with handles would selectively facilitate responses for the hand closest to the
      handle, attempting to replicate a study reported by Tucker and Ellis (1998). We
      also examined whether the hypothesized action priming effects depended upon the
      response hand's proximity to an object. In 7 experiments, participants made
      judgments about whether pictured objects were manmade or natural or whether the
      objects were upright or inverted. They responded by pressing buttons located
      either on the same or opposite side as the objects' handles, at variable
      distances. Action priming was observed only when participants were explicitly
      instructed to imagine picking up the pictured objects while making their
      judgments; the data provide no evidence for task-general automatic priming of
      lateralized responses by object handles. These data indicate that visually
      encoding an object activates spatially localized action representations only
      under special circumstances.

PMID- 25045902
TI  - Movement constraints on interpersonal coordination and communication.
AB  - The present study investigated how constraining movement affects interpersonal
      coordination and joint cognitive performance. Pairs of participants worked
      cooperatively to solve picture-puzzle tasks in which they conversed to identify
      differences between pictures in 3 degree-of-constraint conditions: both
      participants were free to move their hands (free-free; FF); both participants'
      hands were restrained (restrained-restrained; RR); and the hands of 1 participant
      were free while the hands of the other participant were restrained (free
      restrained; FR). Eye tracking data were collected, and movement was measured at
      the waist, hand, and head. Data were analyzed using Cross-Recurrence
      Quantification Analysis (CRQ). Postural sway coordination, gaze coordination, and
      task performance were predicted to be highest in FF, followed by RR, and then by
      FR. Results showed the asymmetric FR condition generally exhibited lesser degrees
      of coordination than the symmetric Conditions FF and RR, and that the patterning
      of coordination in the symmetric conditions varied across the measured body
      segments. These results demonstrate that movement restraints affect not only
      interpersonal postural coordination, but also joint attention. Additionally,
      significant positive relationships were found between task performance and total
      amount of anterior-posterior movement measured at the head, hand and waist;
      number of utterances; and number of differences pairs found in the puzzles. These
      findings indicate a relationship between movement and task performance consistent
      with the hypotheses that both interpersonal coordination and cognitive
      performance are sensitive to local action constraints.

PMID- 25045903
TI  - Stable statistical representations facilitate visual search.
AB  - Observers represent the average properties of object ensembles even when they
      cannot identify individual elements. To investigate the functional role of
      ensemble statistics, we examined how modulating statistical stability affects
      visual search. We varied the mean and/or individual sizes of an array of Gabor
      patches while observers searched for a tilted target. In "stable" blocks, the
      mean and/or local sizes of the Gabors were constant over successive displays,
      whereas in "unstable" baseline blocks they changed from trial to trial. Although
      there was no relationship between the context and the spatial location of the
      target, observers found targets faster (as indexed by faster correct responses
      and fewer saccades) as the global mean size became stable over several displays.
      Building statistical stability also facilitated scanning the scene, as measured
      by larger saccadic amplitudes, faster saccadic reaction times, and shorter
      fixation durations. These findings suggest a central role for peripheral visual
      information, creating context to free resources for detailed processing of
      salient targets and maintaining the illusion of visual stability.

PMID- 25045904
TI  - Invalid retro-cues can eliminate the retro-cue benefit: Evidence for a hybridized
      account.
AB  - The contents of visual working memory (VWM) are capacity limited and require
      frequent updating. The retrospective cueing (retro-cueing) paradigm clarifies how
      directing internal attention among VWM items boosts VWM performance. In this
      paradigm a cue appears prior to retrieval, but after encoding and maintenance.
      The retro-cue effect (RCE) refers to superior VWM after valid versus neutral
      retro-cues. Here we investigated the effect of the invalid retro-cues' inclusion
      on VWM performance. We conducted 2 pairs of experiments, changing both probe type
      (recognition and recall) as well as presence and absence of invalid retro-cue
      trials. Furthermore, to fully characterize these effects over time, we used
      extended post-retro-cue delay durations. In the first set of experiments, probing
      VWM using recognition indicated that the RCE remained consistent in magnitude
      with or without invalid retro-cue trials. In the second set of experiments, VWM
      was probed with recall. Here, the RCE was eliminated when invalid retro-cues were
      included. This finer-grained measure of VWM fidelity showed that all items were
      subject to decay over time. We conclude that the invalid retro-cues impaired the
      protection of validly cues items, but they remain accessible, suggesting greater
      concordance with a prioritization account.

PMID- 25045906
TI  - National dissemination of interpersonal psychotherapy for depression in veterans:
      therapist and patient-level outcomes.
AB  - OBJECTIVE: To evaluate the effects of training in and delivery of interpersonal
      psychotherapy (IPT) for depression throughout the U.S. Department of Veterans
      Affairs health care system on therapists' competency and patients' clinical
      outcomes. METHOD: Participants included 124 therapists and 241 veteran patients.
      Therapists participated in a 3-day workshop followed by 6 months of weekly group
      consultation. Therapy session tapes were rated by expert IPT training consultants
      using a standardized competency rating form. Patient outcomes were assessed with
      the Beck Depression Inventory-II and the World Health Organization Quality of
      Life-BREF. Therapeutic alliance was assessed with the Working Alliance Inventory
      Short Revised. RESULTS: Of the 124 therapists receiving IPT training, 115 (93%)
      completed all training requirements. Therapist competence in IPT increased from
      their 1st patient to their 2nd for both initial (d = 0.36) and intermediate (d =
      0.24) treatment phases. Of the 241 veteran patients treated with IPT, 167 (69%)
      completed >= 12 sessions. Intent-to-treat analyses indicated large overall
      reductions in depression (d = 1.26) and significant improvements in quality of
      life (d = 0.57 to 0.86) and the therapeutic alliance (d = 0.50 to 0.83).
      CONCLUSIONS: National IPT training in the VA health care system was associated
      with significant increases in therapist competencies to deliver IPT, as well as
      large overall reductions in depression and improvements in quality of life among
      veterans, many of whom presented with high levels of depression. RESULTS support
      the feasibility and effectiveness of broad dissemination of IPT in routine
      clinical settings.

PMID- 25045905
TI  - Uncovering the architecture of action semantics.
AB  - Despite research suggesting that stored sensorimotor information about tool use
      is a component of the semantic representations of tools, little is known about
      the action features or organizing principles that underlie this knowledge. We
      used methods similar to those applied in other semantic domains to examine the
      "architecture" of action semantic knowledge. In Experiment 1, participants sorted
      photographs of tools into groups according to the similarity of their associated
      "use" actions and rated tools on dimensions related to action. The results
      suggest that the magnitude of arm movement, configuration of the hand, and manner
      of motion during tool use play a role in determining how tools cluster in action
      "semantic space." In Experiment 2, we validated the architecture uncovered in
      Experiment 1 using an implicit semantic task for which tool use knowledge was not
      ostensibly relevant (blocked cyclic word-picture matching). Using stimuli from
      Experiment 1, we found that participants performed more poorly during blocks of
      trials containing tools used with similar versus unrelated actions, and the
      amount of semantic interference depended on the magnitude of action similarity
      among tools. Thus, the degree of featural overlap between tool use actions plays
      a role in determining the overall semantic similarity of tools.

PMID- 25045907
TI  - Existential therapies: a meta-analysis of their effects on psychological
      outcomes.
AB  - OBJECTIVE: To review the evidence on the efficacy of different types of
      existential therapies: a family of psychological interventions that draw on
      themes from existential philosophy to help clients address such issues in their
      lives as meaning and death anxiety. METHOD: Relevant electronic databases,
      journals, and reference lists were searched for eligible studies. Effects on
      meaning, psychopathology (anxiety and depression), self-efficacy, and physical
      well-being were extracted from each publication or obtained directly from its
      authors. All types of existential therapy for adult samples were included.
      Weighted pooled mean effects were calculated and analyses performed assuming
      fixed-effects model. RESULTS: Twenty-one eligible randomized controlled trials of
      existential therapy were found, from which 15 studies with unique data were
      included, comprising a total of 1,792 participants. Meaning therapies (n = 6
      studies) showed large effects on positive meaning in life immediately
      postintervention (d = 0.65) and at follow-up (d = 0.57), and had moderate effects
      on psychopathology (d = 0.47) and self-efficacy (d = 0.48) at postintervention;
      they did not have significant effects on self-reported physical well-being (n = 1
      study). Supportive-expressive therapy (n = 5) had small effects at posttreatment
      and follow-up on psychopathology (d = 0.20, 0.18, respectively); effects on self
      efficacy and self-reported physical well-being were not significant (n = 1 and n
      = 4, respectively). Experiential-existential (n = 2) and cognitive-existential
      therapies (n = 1) had no significant effects. CONCLUSION: Despite the small
      number and low quality of studies, some existential therapies appear beneficial
      for certain populations. We found particular support for structured interventions
      incorporating psychoeducation, exercises, and discussing meaning in life directly
      and positively with physically ill patients. It is important to study more
      precisely which existential intervention works the best for which individual
      client.

PMID- 25045908
TI  - Stable remission and recovery after acute-phase cognitive therapy for recurrent
      major depressive disorder.
AB  - OBJECTIVE: Continuation-phase cognitive therapy (C-CT) or fluoxetine (FLX)
      reduces relapse in adults with major depressive disorder (MDD; Jarrett,
      Minhajuddin, Gershenfeld, Friedman, & Thase, 2013). Among patients at higher risk
      for relapse, we hypothesized that continuation-phase treatment reduces residual
      symptoms and facilitates stable remission and recovery. METHOD: Outpatients (N =
      241) with recurrent MDD who responded to acute-phase CT with higher risk for
      relapse (i.e., had unstable remission defined by any of the last 7 acute-phase
      scores >= 7 using the Hamilton Rating Scale for Depression; Hamilton, 1960) were
      randomized to 8 months of C-CT, FLX, or pill placebo and followed for 24
      additional months. Psychiatric status ratings (Keller et al., 1987) of 1 or 2
      (absent or minimal depressive symptoms) for 6 and 35 continuous weeks post
      randomization defined stable remission and recovery, respectively. RESULTS:
      Actuarial estimates of stable remission (97%) and recovery (94%) by the end of
      follow-up were high and did not differ among groups. Observed (unadjusted)
      proportions of patients remitting (70%) and recovering (47%) before relapse or
      attrition were lower. During the continuation phase, C-CT (d = 0.21) and FLX (d =
      0.25) patients had significantly lower mean depressive symptoms than did
      controls, but C-CT and FLX patients did not differ from each other, nor did the 3
      experimental groups differ during follow-up. CONCLUSION: Many patients who
      responded to CT with higher relapse risk subsequently remitted and recovered
      after discontinuation of acute-phase treatment. After discontinuation, C-CT and
      FLX decreased levels of residual depressive symptoms, but neither significantly
      increased the likelihood of stable remission or recovery, beyond the moderate to
      high levels observed among patients who did not relapse.

PMID- 25045909
TI  - Weight suppression and body mass index interact to predict long-term weight
      outcomes in adolescent-onset anorexia nervosa.
AB  - Research on anorexia nervosa (AN) has emphasized the importance of low absolute
      body weight, but emerging research suggests the importance of also considering
      low body weight relative to an individual's highest premorbid weight (weight
      suppression; WS). OBJECTIVE: We investigated whether body mass index and WS at
      lowest weight (BMI-LW and WS-LW) among adolescents with AN predicted BMI at 6-,
      10-, or 18-year follow-up, duration of AN, or total eating disorder duration,
      including time during which criteria were met for bulimia nervosa or eating
      disorder not otherwise specified. METHOD: Forty-seven cases of AN identified
      through community screening in Sweden were included. Weight and height data were
      collected from medical records, school nurse charts, and study follow-up
      assessments. RESULTS: Higher WS-LW was associated with higher BMI at 6-year and
      10-year follow-up, and this effect was strongest among those with the lowest BMI
      LW values. BMI-LW and WS-LW were positively associated with BMI at 18-year follow
      up, but there was no significant interaction. There was no significant
      association between WS-LW and AN duration or eating disorder duration, although
      eating disorder duration was longer among those with higher BMI-LW, controlling
      for WS-LW. CONCLUSIONS: Absolute and relative weight status interact to predict
      weight outcomes in AN over the long term. RESULTS suggest that BMI and WS may be
      more relevant to the prediction of long-term weight outcomes than to the
      persistence of other eating disorder symptoms.

PMID- 25045910
TI  - A randomized clinical trial of behavioral couples therapy versus individually
      based treatment for women with alcohol dependence.
AB  - OBJECTIVE: Multiple studies show that behavioral couples therapy (BCT) is more
      efficacious than individually based therapy (IBT) for substance use and
      relationship outcomes among men with alcohol use disorder (AUD). The present
      study compared BCT with IBT for women with AUD. METHOD: Participants were women
      with AUD (N = 105) and their male partners without substance use disorder.
      Participants were mostly White and in their 40s. Women were randomized to equally
      intensive treatments consisting of either BCT plus 12-step-oriented IBT or IBT
      only. Primary outcomes included time line follow-back interview percentage days
      abstinent (PDA) and Inventory of Drug Use Consequences measure of substance
      related problems. Secondary outcomes included the Dyadic Adjustment Scale (DAS),
      Relationship Happiness Scale (RHS), and Revised Conflict Tactics Scales measure
      of intimate partner violence (IPV). Outcome data were collected at baseline,
      posttreatment, and quarterly for 1-year follow-up. RESULTS: Compared with IBT
      only, BCT plus IBT had significantly better primary outcomes of higher PDA and
      fewer substance-related problems during the 1-year follow-up period. Compared
      with IBT only, BCT had significantly higher male RHS during the 1-year follow-up.
      Women with lower pretreatment DAS had significantly higher DAS following BCT
      versus IBT, and there was an increasing advantage for BCT on female DAS over the
      follow-up. IPV was significantly reduced from pretreatment to follow-up, with no
      differences between treatment conditions. CONCLUSION: RESULTS showed that BCT for
      women with AUD was more efficacious than IBT in reducing substance use and
      substance-related problems and improving partner relationships.

PMID- 25045911
TI  - An idiographic analysis of change processes in the unified transdiagnostic
      treatment of depression.
AB  - Idiographic research methods can provide rich information regarding the process
      of change in specific treatments. OBJECTIVE: Adopting an idiographic, exploratory
      approach, this study examined (a) temporal patterns of 3 transdiagnostic change
      constructs (mindfulness, cognitive reappraisal, and emotion avoidance), (b) the
      relationships between these constructs and depression and anxiety symptom
      severity over time, and (c) changes in these constructs in relation to the
      introduction of specific transdiagnostic intervention strategies in a single
      case. METHOD: The case was a 64-year-old, White, female patient with principal
      major depressive disorder and secondary generalized anxiety disorder being
      treated with the Unified Protocol (UP). Univariate and multivariate time series
      analyses were applied to symptom and change construct data. RESULTS: (a)
      Clinically significant decreases in depression and anxiety from baseline to
      posttreatment were observed, as well as clinically significant increases in
      mindfulness and reappraisal; (b) changes in mindfulness were associated with
      changes in depression and anxiety, and changes in mindfulness temporally preceded
      changes in depression and anxiety; (c) changes in reappraisal were associated
      with changes in depression, and changes in reappraisal temporally preceded
      changes in depression; (d) the UP module designed to increase present-focused
      emotion awareness exerted the strongest influence on mindfulness ratings,
      although other modules had an impact; (e) reappraisal ratings were most strongly
      influenced by the emotion monitoring and functional analysis module, although
      subsequent modules continued to have a measureable impact. CONCLUSIONS: Although
      specific to this case, these results begin to elucidate important processes of
      change in transdiagnostic cognitive-behavioral therapy for principal depression
      with comorbid anxiety.

PMID- 25045912
TI  - Developmental transitions in presentations of externalizing problems among boys
      and girls at risk for child maltreatment.
AB  - The present study examined the impact of children's maltreatment experiences on
      the emergence of externalizing problem presentations among children during
      different developmental periods. The sample included 788 youth and their
      caregivers who participated in a multisite, prospective study of youth at-risk
      for maltreatment. Externalizing problems were assessed at ages 4, 8, and 12, and
      symptoms and diagnoses of attention-deficit/hyperactivity disorder, oppositional
      defiant disorder, and conduct disorder were assessed at age 14, during interviews
      with youth and caregivers. Information about maltreatment allegations was coded
      from official records. Latent transition analysis identified three groups of
      youth with similar presentations of externalizing problems ("well adjusted,"
      "hyperactive/oppositional," and "aggressive/rule-breaking") and transitions
      between groups from ages 4, 8, and 12. A "defiant/deceitful" group also emerged
      at age 12. Girls were generally more likely to present as well adjusted than
      boys. Children with recent physical abuse allegations had an increased risk for
      aggressive/rule-breaking presentations during the preschool and preadolescent
      years, while children with sexual abuse or neglect allegations had lower
      probabilities of having well-adjusted presentations during middle childhood.
      These findings indicate that persistently severe aggressive conduct problems,
      which are related to the most concerning outcomes, can be identified early,
      particularly among neglected and physically and sexually abused children. 

PMID- 25045913
TI  - Multi-step preparation technique to recover multiple metabolite compound classes
      for in-depth and informative metabolomic analysis.
AB  - Metabolomics is an emerging field which enables profiling of samples from living
      organisms in order to obtain insight into biological processes. A vital aspect of
      metabolomics is sample preparation whereby inconsistent techniques generate
      unreliable results. This technique encompasses protein precipitation, liquid
      liquid extraction, and solid-phase extraction as a means of fractionating
      metabolites into four distinct classes. Improved enrichment of low abundance
      molecules with a resulting increase in sensitivity is obtained, and ultimately
      results in more confident identification of molecules. This technique has been
      applied to plasma, bronchoalveolar lavage fluid, and cerebrospinal fluid samples
      with volumes as low as 50 ul.  Samples can be used for multiple downstream
      applications; for example, the pellet resulting from protein precipitation can be
      stored for later analysis. The supernatant from that step undergoes liquid-liquid
      extraction using water and strong organic solvent to separate the hydrophilic and
      hydrophobic compounds. Once fractionated, the hydrophilic layer can be processed
      for later analysis or discarded if not needed. The hydrophobic fraction is
      further treated with a series of solvents during three solid-phase extraction
      steps to separate it into fatty acids, neutral lipids, and phospholipids. This
      allows the technician the flexibility to choose which class of compounds is
      preferred for analysis. It also aids in more reliable metabolite identification
      since some knowledge of chemical class exists. 

PMID- 25045914
TI  - Evaluation of measures of correctness of genotype imputation in the context of
      genomic prediction: a review of livestock applications.
AB  - In livestock, many studies have reported the results of imputation to 50k single
      nucleotide polymorphism (SNP) genotypes for animals that are genotyped with low
      density SNP panels. The objective of this paper is to review different measures
      of correctness of imputation, and to evaluate their utility depending on the
      purpose of the imputed genotypes. Across studies, imputation accuracy, computed
      as the correlation between true and imputed genotypes, and imputation error
      rates, that counts the number of incorrectly imputed alleles, are commonly used
      measures of imputation correctness. Based on the nature of both measures and
      results reported in the literature, imputation accuracy appears to be a more
      useful measure of the correctness of imputation than imputation error rates,
      because imputation accuracy does not depend on minor allele frequency (MAF),
      whereas imputation error rate depends on MAF. Therefore imputation accuracy can
      be better compared across loci with different MAF. Imputation accuracy depends on
      the ability of identifying the correct haplotype of a SNP, but many other factors
      have been identified as well, including the number of genotyped immediate
      ancestors, the number of animals with genotypes at the high-density panel, the
      SNP density on the low- and high-density panel, the MAF of the imputed SNP and
      whether imputed SNP are located at the end of a chromosome or not. Some of these
      factors directly contribute to the linkage disequilibrium between imputed SNP and
      SNP on the low-density panel. When imputation accuracy is assessed as a predictor
      for the accuracy of subsequent genomic prediction, we recommend that: (1)
      individual-specific imputation accuracies should be used that are computed after
      centring and scaling both true and imputed genotypes; and (2) imputation of gene
      dosage is preferred over imputation of the most likely genotype, as this
      increases accuracy and reduces bias of the imputed genotypes and the subsequent
      genomic predictions. 

PMID- 25045915
TI  - Integrated field lysimetry and porewater sampling for evaluation of chemical
      mobility in soils and established vegetation.
AB  - Potentially toxic chemicals are routinely applied to land to meet growing demands
      on waste management and food production, but the fate of these chemicals is often
      not well understood. Here we demonstrate an integrated field lysimetry and
      porewater sampling method for evaluating the mobility of chemicals applied to
      soils and established vegetation. Lysimeters, open columns made of metal or
      plastic, are driven into bareground or vegetated soils. Porewater samplers, which
      are commercially available and use vacuum to collect percolating soil water, are
      installed at predetermined depths within the lysimeters. At prearranged times
      following chemical application to experimental plots, porewater is collected, and
      lysimeters, containing soil and vegetation, are exhumed. By analyzing chemical
      concentrations in the lysimeter soil, vegetation, and porewater, downward
      leaching rates, soil retention capacities, and plant uptake for the chemical of
      interest may be quantified. Because field lysimetry and porewater sampling are
      conducted under natural environmental conditions and with minimal soil
      disturbance, derived results project real-case scenarios and provide valuable
      information for chemical management. As chemicals are increasingly applied to
      land worldwide, the described techniques may be utilized to determine whether
      applied chemicals pose adverse effects to human health or the environment. 

PMID- 25045916
TI  - Compensatory limb use and behavioral assessment of motor skill learning following
      sensorimotor cortex injury in a mouse model of ischemic stroke.
AB  - Mouse models have become increasingly popular in the field of behavioral
      neuroscience, and specifically in studies of experimental stroke. As models
      advance, it is important to develop sensitive behavioral measures specific to the
      mouse. The present protocol describes a skilled motor task for use in mouse
      models of stroke. The Pasta Matrix Reaching Task functions as a versatile and
      sensitive behavioral assay that permits experimenters to collect accurate outcome
      data and manipulate limb use to mimic human clinical phenomena including
      compensatory strategies (i.e., learned non-use) and focused rehabilitative
      training. When combined with neuroanatomical tools, this task also permits
      researchers to explore the mechanisms that support behavioral recovery of
      function (or lack thereof) following stroke. The task is both simple and
      affordable to set up and conduct, offering a variety of training and testing
      options for numerous research questions concerning functional outcome following
      injury. Though the task has been applied to mouse models of stroke, it may also
      be beneficial in studies of functional outcome in other upper extremity injury
      models. 

PMID- 25045917
TI  - Targeting both viral and host determinants of human immunodeficiency virus entry,
      using a new lentiviral vector coexpressing the T20 fusion inhibitor and a
      selective CCL5 intrakine.
AB  - Numerous strategies targeting early and late steps of the HIV life cycle have
      been proposed for gene therapy. However, targeting viral and host determinants of
      HIV entry is the only strategy that would prevent viral DNA-mediated CD4(+) cell
      death while diminishing the possibility for the virus to escape. To this end, we
      devised a bicistronic lentiviral vector expressing the membrane-bound form of the
      T20 fusion inhibitor, referred to as the C46 peptide, and a CCR5 superagonist,
      modified to sequester CCR5 away from the cell surface, referred to as the P2-CCL5
      intrakine. We tested the effects of the vector on HIV infection and replication,
      using the human CEMR5 cell line expressing CD4 and CCR5, and primary human T
      cells. Transduced cells expressed the C46 peptide, detected with the 2F5
      monoclonal antibody by flow cytometry. Expression of the P2-CCL5 intrakine
      correlates with lower levels of cell surface CCR5. Complete protection against
      HIV infection could be observed in cells expressing the protective transgenes.
      Importantly, we show that the combination of the transgenes was more potent than
      either transgene alone, showing the interest of expressing two entry inhibitors
      to inhibit HIV infection. Last, genetically modified cells possessed a selective
      advantage over nonmodified cells on HIV challenge in vitro, showing that modified
      cells were protected from HIV-induced cell death. Our results demonstrate that
      lentiviral vectors coexpressing the T20 fusion inhibitor and the P2-CCL5
      intrakine represent promising tools for HIV gene therapy.

PMID- 25045918
TI  - Women's views on wet nursing and milk siblinghood: an example from Turkey.

PMID- 25045919
TI  - A novel surgical technique for preserving the bladder neck during robot-assisted
      laparoscopic radical prostatectomy: preliminary results.
AB  - PURPOSE: To describe our new surgical technique for preserving the bladder neck
      during robot-assisted laparoscopic prostatectomy (RALP) and to present the
      anatomy between the bladder neck and prostate. METHODS: Between December 2012 and
      May 2014, 52 RALPs were performed at our institute. Demographic, perioperative,
      and postoperative data were recorded. Quality of life (QoL) scores were assessed
      before RALP, after urethral catheter removal, and at the first month after RALP.
      Fatty connective tissue between bladder neck and prostate was introduced, and
      circular muscle fibers of the internal sphincter were seen in all patients.
      Complications were classified according to the Clavien-Dindo classification.
      Statistical analyses were performed. RESULTS: Mean follow-up was 9.6+/-5.2
      months; mean age was 61.1+/-6.5 years. Our novel surgical technique for
      preserving the bladder neck was performed in 52 patients, and they were continent
      after catheter removal; mean duration of the catheter was 9.4+/-1.4 days. There
      was a significant difference in QoL before RALP and after catheter removal,
      however, but there was no statistical difference between before and 1 month after
      RALP (respectively; P<0.001, P=0.5). Furthermore, there was no complication
      related to the bladder neck such as bladder neck stricture, acute/chronic urinary
      retention, as well as no Clavien III, IV, and V complications. In addition,
      conventional laparoscopy and/or open surgery was not needed in any of the RALP
      cases. CONCLUSION: Our novel technique provided very early continence at the time
      of catheter removal after RALP within short-term follow-up. This can help early
      recovery and develop QoL scores after RALP.

PMID- 25045920
TI  - Polyphyllin D induces apoptosis in U87 human glioma cells through the c-Jun NH2
      terminal kinase pathway.
AB  - Polyphyllin D (PD), an active component from a traditional medicinal herb Paris
      polyphylla, which has long been used for the treatment of cancer in Asian
      countries, has been found to hold significant antitumor activity in vivo or in
      vitro. However, there were few reports on the effects and underlying mechanism of
      PD on apoptosis in U87 human glioma cells. The present study was conducted to
      evaluate apoptotic induction of PD in U87 human glioma cells, and explore its
      underlying pathway. U87 glioma cells were cultured and treated with varied
      concentrations of PD (from 10(-8) to 10(-4) M). The inhibition of U87 glioma cell
      proliferation by PD was assessed by MTT assay. The apoptosis of U87 glioma cells
      was detected by flow cytometry, and western blot analysis was used to examine
      human B-cell leukemia/lymphoma 2 (Bcl-2), human Bcl-2 associated X protein (Bax),
      caspase-3, total-c-jun NH2-terminal kinase (t-JNK), and phosphorylation-JNK (p
      JNK) protein expression in U87 human glioma cells. The treatment with PD for 24 h
      significantly inhibited the proliferation of U87 human glioma cells in a
      concentration-dependent manner. PD increased apoptosis and significantly
      upregulated the expression of Bax, caspase-3, and p-JNK associated with
      apoptosis, but downregulated antiapoptotic Bcl-2 expression in U87 human glioma
      cells. Our data provided evidences that PD induces apoptosis in U87 human glioma
      cells. This effect might be associated with the JNK pathway.

PMID- 25045921
TI  - Low-level laser therapy supported surgical treatment of bisphosphonate related
      osteonecrosis of jaws: a retrospective analysis of 11 cases.
AB  - OBJECTIVE: The aim of this study is to evaluate and report on low-level laser
      therapy (LLLT) supported medical-surgical treatment outcomes of 11 patients with
      bisphosphonate related osteonecrosis of the jaws (BRONJ) lesions. BACKGROUND
      DATA: BRONJ is a severe clinical condition, which adversely affects patients'
      lives. Even though various treatment modalities have been proposed, the ideal
      approach still remains to be debated. LLLT stands out among supportive approaches
      because of its favorable effects on tissue healing. MATERIALS AND METHODS: Eleven
      patients diagnosed with Stage II or III lesions (American Association of Oral and
      Maxillofacial Surgeons [AAOMS] classification) were included in the study. All
      patients received LLLT applications during the postoperative period in addition
      to medical and surgical treatment. Laser applications covering the entirety of
      the surgical site were performed with GaAlAs diode laser with the following
      parameters: 808 nm wavelength, 0.5 W power, continuous wave, noncontact mode at
      0.5-1 cm distance from the oral mucosa, spot size 0.28 cm(2) (R=6 mm), for 3 sec
      per point (10 sec per cm(2)), and energy density of 5 J/cm(2) (energy per
      point,1.4 J). RESULTS: Elimination of previously recorded symptoms and a stable
      mucosal closure was achieved in all patients. Primary healing was achieved in
      seven patients and secondary healing course was observed in four patients.
      Permanence of obtained positive outcomes was noted in follow-up periods.
      CONCLUSIONS: Treatment of advanced BRONJ lesions with a combination of antibiotic
      therapy, surgical removal of the lesion, and consecutive low-level diode laser
      applications provided favorable results in all patients. In consideration of our
      findings, it can be assumed that LLLT may serve as a safe and effective adjunct
      to medical-surgical treatment of BRONJ lesions.

PMID- 25045922
TI  - Do n-3 polyunsaturated fatty acids increase or decrease lipid peroxidation in
      humans?
AB  - Abstract Background: Despite many known health benefits of n-3 polyunsaturated
      fatty acids (PUFA), there is a concern that their high degree of unsaturation may
      actually increase oxidative stress, lipid peroxidation (LPO), and chronic
      inflammatory diseases. METHODS: In this review, we have analyzed results from
      published human studies regarding the effects of n-3 PUFA supplementation on
      markers of lipid peroxidation. RESULTS: Of the 22 published human studies, nine
      found no change, eight a decrease, and five an increase in markers of LPO. These
      inconsistencies may be due to methods, subject characteristics, dose, duration,
      fatty acid and antioxidant composition of supplements, and basal diets. METHODS
      used for analysis seem to be the most significant factor. Six of eight studies
      with a decrease in LPO determined F2-isoprostanes produced in vivo, and two
      determined plasma antioxidant capacity or hydroperoxides. n-3 PUFA can serve as
      scavengers for free radicals and also modulate expression of genes that determine
      the balance between oxidative and antioxidative status. Recent studies that
      monitored oxidation products of cholesterol and fatty acids support the
      hypothesis that n-3 PUFA decrease LPO. Most of the studies showing no change or
      increase in LPO determined markers that involved ex vivo sample preparation or
      oxidation (malondialdehyde, low-density lipoprotein oxidation, lipid
      hydroperoxides). CONCLUSION: A majority of studies do not indicate that n-3 PUFA
      increased LPO. Future studies need to investigate the effects of dose, duration,
      and composition of n-3 PUFA with standardized diets and methods on concentrations
      and types of LPO products produced.

PMID- 25045923
TI  - Safety, efficacy and toxicological evaluation of a novel, patented anti-diabetic
      extract of Trigonella Foenum-Graecum seed extract (Fenfuro).
AB  - Safety and anti-diabetic efficacy of a novel, proprietary Trigonella foenum
      graecum seed extract [novel fenugreek extract (FE), FenfuroTM, CR0010810)
      enriched in furostanolic saponins (>60% w/w, HPLC) were assessed. Concerning
      safety, we undertook studies dealing with acute oral toxicity, 28-d sub-chronic
      toxicity and Ames' bacterial reverse mutation assay that revealed no toxicity.
      Concerning efficacy, we examined beneficial effects of the extract on rats with
      type 2 diabetes (T2D). Male Sprague-Dawley rats received a high-fat diet for 2
      weeks followed by streptozotocin (STZ, 35 mg/kg i.p.) to produce T2D. Seven days
      post-STZ, rats showing >=300 mg/dl fasting plasma glucose level (PGL) were
      included in the study. FE (150- or 450- mg/kg p.o.) and glipizide (5 mg/kg p.o.)
      were administered once daily for 20 d and then twice daily for another 10 d
      (total 30 d). Blood samples were collected at 0, 10, 20 and 30 d of treatment and
      estimated for fasting plasma triglyceride (PTG), total cholesterol and insulin
      levels. After 30 d, FE and glipizide-treated diabetic animals were treated in
      combination with or without metformin (100 mg/kg) twice daily for another 10 d.
      FE did not influence body weight, feed and water intake. FE (150 mg/kg p.o.)
      reduced PTG levels in T2D rats by 22%, 24.6% and 29% at 10, 20 and 30 d of
      treatment, respectively, while glipizide (5 mg/kg p.o.) reduced the PTG levels by
      57.4%, 46.2% and 39.4% at these time points. FE (450 mg/kg) treatment in STZ
      induced diabetic rats produced significant hypoglycemic activity (approximately
      31.5%) as compared to insulin (48.2% with 1 U/kg i.p.). FE (150 mg/kg p.o.) and
      metformin (100 mg/kg p.o.) combined produced significant reduction (20.7%) of PGL
      in T2D rats. No adverse effects were observed. We conclude after extensive in
      vitro and in vivo safety and efficacy studies that FE is safe and effective in
      treating T2D.

PMID- 25045924
TI  - An exploration of the existential experiences of patients following curative
      treatment for cancer: reflections from a U.K. Sample.
AB  - The existential experiences associated with cancer diagnosis and treatment are
      well researched, but the posttreatment phase is relatively underexplored. Using
      semistructured interviews and theory-led thematic analysis this qualitative study
      investigated the existential experiences of eight cancer survivors who had
      successfully completed curative treatment. Being in remission had led to deep
      existential reflections (i.e., death anxiety, freedom, isolation, and meaning
      making), and some participants faced considerable challenges that affected their
      emotional well-being. Understanding cancer survivors' existential challenges
      should enable health care professionals to engage with the emerging shift from
      the predominantly medically focused posttreatment care to a more holistic
      approach. 

PMID- 25045925
TI  - Preparation and characterization of photo-responsive cell-penetrating peptide
      mediated nanostructured lipid carrier.
AB  - Tumor-oriented nanocarrier drug delivery approaches with photo-sensitivity have
      been drawing considerable attention over the years. Here we described a
      nanostructured lipid carrier (NLC) modified with photo-responsive cell
      penetrating peptides (pCPP-NLC). The conventional cell penetrating peptide (CPP)
      mediated intracellular drug delivery system sometimes seemed limited due to the
      lack of target selectivity of the cell penetrating activity. In this study, pCPP
      (CKRRMK(Nvoc)WK(Nvo0c)K(Nvoc)), a photo-responsive CPP originated from the CPP
      (CKRRMKWKK), was endowed photo-responsiveness after masking of lysines in the
      sequence of CPP with photolabile-protective groups, and was introduced onto the
      surface of NLC. Accordingly, upon reaching the tumor tissues, pCPP-NLC enhance
      specific cancer cellular uptake after rapidly cleaving the photolabile-protective
      group, in this case, illumination in the presence of UV-light. In contrast, in
      circulation, the penetration was shielded. The pCPP-NLC carrying paclitaxel (PTX)
      prepared in this work possessed suitable physiochemical properties such as small
      particle size, high drug encapsulation efficiency, and good stability. The strong
      cellular uptake and cytotoxic activity of pCPP-NLC in HT-1080 cells verified the
      correlation with illumination. The remarkable penetration into HT-1080
      multicellular tumor spheroids confirmed that the temporary mask of the
      photolabile-protective group in pCPP does not disturb the penetration ability of
      CPP in the tumor microenvironment with illumination. Furthermore, the triggered
      activation exhibited higher antitumor efficacy with the tumor spheroids compared
      with the non-modified NLC (N-NLC) and Taxol((r)). In conclusion, the application
      of pCPP modifications may be an approach for the selectively targeted delivery of
      anti-tumor agents.

PMID- 25045926
TI  - Methazolamide-loaded solid lipid nanoparticles modified with low-molecular weight
      chitosan for the treatment of glaucoma: vitro and vivo study.
AB  - The aims of this study were to design and characterize methazolamide (MTZ)-loaded
      solid lipid nanoparticles (SLN) with and without modification of low molecular
      weight chitosan (CS) and compare their potentials for ocular drug delivery. Low
      molecular weight CS was obtained via a modified chemical oxidative degradation
      method. SLN with CS (CS-SLN-MTZ) and without CS (SLN-MTZ) were prepared according
      to a modified emulsion-solvent evaporation method. SLN-MTZ and CS-SLN-MTZ were
      199.4 +/- 2.8 nm and 252.8 +/- 4.0 nm in particle size, -21.3 +/- 1.9 mV and
      +31.3 +/- 1.7 mV in zeta potential, respectively. Physical stability studies
      demonstrated that CS-SLN-MTZ remained stable for at least 4 months at 4  degrees
      C, while SLN-MTZ no more than 2 months. A prolonged in vitro release profile of
      MTZ from CS-SLN-MTZ was obtained compared with SLN-MTZ. Furthermore, CS-SLN-MTZ
      presented a better permeation property in excised rabbit cornea. In vivo studies
      indicated that the intraocular pressure lowering effect of CS-SLN-MTZ (245.75 +/-
      18.31 mmHg * h) was significantly better than both SLN-MTZ (126.74 +/- 17.73 mmHg
      * h) and commercial product Brinzolamide Eye Drops AZOPT(r) (171.17 +/- 16.45
      mmHg * h). The maximum percentage decrease in IOP of CS-SLN-MTZ (42.78 +/- 7.71%)
      was higher than SLN-MTZ (27.82 +/- 4.15%) and was comparable to AZOPT (38.06 +/-
      1.25%). CS-SLN-MTZ showed no sign of ocular irritancy according to the Draize
      method and the histological examination.

PMID- 25045927
TI  - Risk factors of hypertensive pregnancies in women with diabetes and the influence
      on their future life.
AB  - Diabetic women carry a 2-4 times increased risk of a hypertensive pregnancy
      compared to non-diabetic people. This risk is related to presence of diabetic
      nephropathy, but also poor glycaemic control. Efforts to improve glycaemic
      control have decreased perinatal morbidity and mortality related to diabetic
      nephropathy. Despite good glycaemic control, overt nephropathy is associated with
      a variety of pregnancy complications, such as fetal growth restriction and pre
      eclampsia. General population studies show that women with a history of pre
      eclampsia are more prone to develop cardiovascular disease later in life than
      women with a history of normotensive pregnancy. Furthermore, recent data
      regarding the long-term effects of hypertensive pregnancies on late diabetic
      complications indicate that these women should be followed and treatment should
      be started early. In this review we summarize data on risk factors and long-term
      effects of hypertensive pregnancies on late diabetic complications that may be of
      clinical relevance in the prevention of these complications.

PMID- 25045929
TI  - Human adenovirus-36 is uncommon in type 2 diabetes and is associated with
      increased insulin sensitivity in adults in Sweden.
AB  - BACKGROUND: Human adenovirus-36 (Adv36) increases adiposity, but also upregulates
      distal insulin signaling in vitro in human adipose and muscle tissue and in vivo
      in the rodent independently of adiposity. Accordingly, healthy adults and
      children with antibodies against Adv36 had increased insulin sensitivity and
      reduced hepatic lipid accumulation. We hypothesized that Adv36 infection would be
      less frequent in individuals with type 2 diabetes or impaired glycemic control.
      METHODS: Presence of antibodies against Adv36 was analyzed for association to
      type 2 diabetes or impaired glycemic control in a two-wave population-based
      sample of well-characterized adults (n = 1734). Indices of impaired glycemic
      control included oral glucose tolerance, and circulating fasting levels of
      glucose, insulin, and insulin-like growth factor binding protein-1 (IGFBP-1).
      RESULTS: Adv36 seropositivity was more common in those with normal glucose
      tolerance (NGT) than in those with diabetes (females: OR 17.2, 95% CI 4.0-74.3;
      males: OR 3.5, 95% CI 1.8-6.7). Also, females with NGT had higher frequency of
      Adv36 seropositivity than females with prediabetes (impaired glucose tolerance
      and/or impaired fasting glucose; OR 1.8, 95% CI 1.1-3.1). Within the female
      prediabetes group Adv36 seropositivity was associated with higher insulin
      sensitivity reflected by reduced HOMA-IR and increased IGFBP-1. CONCLUSION: Adv36
      infection is associated with lower occurrence of type 2 diabetes and better
      insulin sensitivity in adults, particularly among females.

PMID- 25045930
TI  - Cortical source analysis of high-density EEG recordings in children.
AB  - EEG is traditionally described as a neuroimaging technique with high temporal and
      low spatial resolution. Recent advances in biophysical modelling and signal
      processing make it possible to exploit information from other imaging modalities
      like structural MRI that provide high spatial resolution to overcome this
      constraint. This is especially useful for investigations that require high
      resolution in the temporal as well as spatial domain. In addition, due to the
      easy application and low cost of EEG recordings, EEG is often the method of
      choice when working with populations, such as young children, that do not
      tolerate functional MRI scans well. However, in order to investigate which neural
      substrates are involved, anatomical information from structural MRI is still
      needed. Most EEG analysis packages work with standard head models that are based
      on adult anatomy. The accuracy of these models when used for children is limited,
      because the composition and spatial configuration of head tissues changes
      dramatically over development. In the present paper, we provide an overview of
      our recent work in utilizing head models based on individual structural MRI scans
      or age specific head models to reconstruct the cortical generators of high
      density EEG. This article describes how EEG recordings are acquired, processed,
      and analyzed with pediatric populations at the London Baby Lab, including
      laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel
      level and source analysis.

PMID- 25045931
TI  - Joint effects of ambient air pollutants on pediatric asthma emergency department
      visits in Atlanta, 1998-2004.
AB  - BACKGROUND: Because ambient air pollution exposure occurs as mixtures,
      consideration of joint effects of multiple pollutants may advance our
      understanding of the health effects of air pollution. METHODS: We assessed the
      joint effect of air pollutants on pediatric asthma emergency department visits in
      Atlanta during 1998-2004. We selected combinations of pollutants that were
      representative of oxidant gases and secondary, traffic, power plant, and criteria
      pollutants, constructed using combinations of criteria pollutants and fine
      particulate matter (PM2.5) components. Joint effects were assessed using
      multipollutant Poisson generalized linear models controlling for time trends,
      meteorology, and daily nonasthma upper respiratory emergency department visit
      counts. Rate ratios (RRs) were calculated for the combined effect of an
      interquartile range increment in each pollutant's concentration. RESULTS:
      Increases in all of the selected pollutant combinations were associated with
      increases in warm-season pediatric asthma emergency department visits (eg, joint
      effect RR = 1.13 [95% confidence interval = 1.06-1.21] for criteria pollutants,
      including ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, and PM2.5).
      Cold-season joint effects from models without nonlinear effects were generally
      weaker than warm-season effects. Joint-effect estimates from multipollutant
      models were often smaller than estimates based on single-pollutant models, due to
      control for confounding. Compared with models without interactions, joint-effect
      estimates from models including first-order pollutant interactions were largely
      similar. There was evidence of nonlinear cold-season effects. CONCLUSIONS: Our
      analyses illustrate how consideration of joint effects can add to our
      understanding of health effects of multipollutant exposures and also illustrate
      some of the complexities involved in calculating and interpreting joint effects
      of multiple pollutants.

PMID- 25045933
TI  - Quantitative proteomics using reductive dimethylation for stable isotope
      labeling.
AB  - Stable isotope labeling of peptides by reductive dimethylation (ReDi labeling) is
      a method to accurately quantify protein expression differences between samples
      using mass spectrometry. ReDi labeling is performed using either regular (light)
      or deuterated (heavy) forms of formaldehyde and sodium cyanoborohydride to add
      two methyl groups to each free amine. Here we demonstrate a robust protocol for
      ReDi labeling and quantitative comparison of complex protein mixtures. Protein
      samples for comparison are digested into peptides, labeled to carry either light
      or heavy methyl tags, mixed, and co-analyzed by LC-MS/MS. Relative protein
      abundances are quantified by comparing the ion chromatogram peak areas of heavy
      and light labeled versions of the constituent peptide extracted from the full MS
      spectra. The method described here includes sample preparation by reversed-phase
      solid phase extraction, on-column ReDi labeling of peptides, peptide
      fractionation by basic pH reversed-phase (BPRP) chromatography, and StageTip
      peptide purification. We discuss advantages and limitations of ReDi labeling with
      respect to other methods for stable isotope incorporation. We highlight novel
      applications using ReDi labeling as a fast, inexpensive, and accurate method to
      compare protein abundances in nearly any type of sample. 

PMID- 25045928
TI  - Systematic reviews and meta-analyses for more profitable strategies in peripheral
      artery disease.
AB  - In the peripheral arteries, a thrombus superimposed on atherosclerosis
      contributes to the progression of peripheral artery disease (PAD), producing
      intermittent claudication (IC), ischemic necrosis, and, potentially, loss of the
      limb. PAD with IC is often undiagnosed and, in turn, undertreated. The low
      percentage of diagnosis (~30%) in this setting of PAD is of particular concern
      because of the potential worsening of PAD (amputation) and the high risk of
      adverse vascular outcomes (vascular death, coronary artery disease, stroke). A
      Medline literature search of the highest-quality systematic reviews and meta
      analyses of randomized controlled trials documents that, due to risk of bias,
      imprecision, and indirectness, the overall quality of the evidence concerning
      diagnostic tools and antithrombotic interventions in PAD is generally low. Areas
      of research emerge from the information collected. Appropriate treatments for PAD
      patients will only derive from ad-hoc studies. Innovative imaging techniques are
      needed to identify PAD subjects at the highest vascular risk. Whether IC
      unresponsive to physical exercise and smoking cessation identifies those with a
      heritable predisposition to more severe vascular events deserves to be addressed.
      Devising ways to improve prevention of vascular events in patients with PAD
      implies a co-ordinated approach in vascular medicine.

PMID- 25045934
TI  - Perceived reactions of elementary school students to changes in school lunches
      after implementation of the United States Department of Agriculture's new meals
      standards: minimal backlash, but rural and socioeconomic disparities exist.
AB  - BACKGROUND: Updated standards for meals sold through the USDA's National School
      Lunch Program took effect at the beginning of the 2012-2013 school year. The
      current study assessed the perceptions of school staff regarding student
      reactions to these changes in school lunches and how perceptions varied across
      schools. METHODS: Mailback surveys were gathered from administrators and food
      service staff at a nationally representative sample of 557 US public elementary
      schools in the second half of the 2012-2013 school year. RESULTS: Half of the
      respondents (56.4%) agreed that students complained about the meals at first, but
      70% agreed that students like the new lunches. Perceived student complaints were
      significantly higher among respondents from rural schools (n=184) than from urban
      (n=127) or suburban (n=171) schools. Respondents at rural schools also were more
      likely to report that they perceived that fewer students were purchasing the
      meals and that students were consuming less of the meals than during the previous
      year. Perceived student complaints were higher at schools not offering regular
      (i.e., higher-fat) pizza. Respondents at socioeconomically disadvantaged schools
      (>66% of students eligible for free/reduced-priced meals) perceived that more
      students were buying lunch and that students were eating more of the meal than in
      the previous year. CONCLUSIONS: Perceptions of school personnel suggest
      reasonable acceptance of school lunches subsequent to revisions. Given the
      importance of offering healthful foods at school, the revised USDA meals
      standards are a promising strategy to improve the diets of children.

PMID- 25045935
TI  - Occurrence, exposure, effects, recommended intake and possible dietary use of
      selected trace compounds (aluminium, bismuth, cobalt, gold, lithium, nickel,
      silver).
AB  - BACKGROUND: Minerals, metals, clays and rocks were widely used by physicians in
      the past. However, it was and it is well known that some inorganic elements at
      high dosage may have curative effects but also serious toxicity. The effects at
      low or ultra-low concentrations, on the contrary, are less documented, but the
      idea that low dosage supplementation might be beneficial to human health is
      widespread even in the present period. METHODS: The main information about
      aluminium, bismuth, cobalt, gold, lithium, nickel and silver was selected and
      evaluated from a vast body of medical literature. RESULTS: In modern times, most
      elements are proposed for human use at levels comparable with normal dietary
      intake, probably for precautionary considerations. CONCLUSION: Some inorganic
      trace compounds might have unexpected effects at extremely low dosages, but
      scientific demonstrations of beneficial effects of supplementation are mostly not
      available in the medical literature.

PMID- 25045936
TI  - Egg intake during carbohydrate restriction alters peripheral blood mononuclear
      cell inflammation and cholesterol homeostasis in metabolic syndrome.
AB  - Egg yolk contains bioactive components that improve plasma inflammatory markers
      and HDL profiles in metabolic syndrome (MetS) under carbohydrate restriction. We
      further sought to determine whether egg yolk intake affects peripheral blood
      mononuclear cell (PBMC) inflammation and cholesterol homeostasis in MetS, as HDL
      and its associated lipid transporter ATP-binding cassette transporter A1 (ABCA1)
      reduce the inflammatory potential of leukocytes through modulation of cellular
      cholesterol content and distribution. Thirty-seven men and women classified with
      MetS consumed a moderate carbohydrate-restricted diet (25%-30% of energy) for 12
      weeks, in addition to consuming either three whole eggs per day (EGG) or the
      equivalent amount of yolk-free egg substitute (SUB). Interestingly,
      lipopolysaccharide-induced PBMC IL-1beta and TNFalpha secretion increased from
      baseline to week 12 in the SUB group only, despite increases in PBMC toll-like
      receptor 4 (TLR4) mRNA expression in the EGG group. Compared to baseline, ABCA1
      and 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression increased by
      week 12 in the EGG group only, whereas changes in PBMC total cholesterol
      positively correlated with changes in lipid raft content. Together, these
      findings suggest that intake of whole eggs during carbohydrate restriction alters
      PBMC inflammation and cholesterol homeostasis in MetS. 

PMID- 25045937
TI  - Chemopreventive effects of oplopantriol A, a novel compound isolated from
      Oplopanax horridus, on colorectal cancer.
AB  - Oplopanax horridus is a North American botanical that has received limited
      investigations. We previously isolated over a dozen of the constituents from O.
      horridus, and among them oplopantriol A (OPT A) is a novel compound. In this
      study, we firstly evaluated the in vivo chemoprevention activities of OPT A using
      the xenograft colon cancer mouse model. Our data showed that this compound
      significantly suppressed tumor growth with dose-related effects (p < 0.01). Next,
      we characterized the compound's growth inhibitory effects in human colorectal
      cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells
      were significantly inhibited in both a concentration- and time-dependent manner
      (both p < 0.01). The IC50 was approximately 5 uM for HCT-116 and 7 uM for SW-480
      cells. OPT A significantly induced apoptosis and arrested the cell cycle at the
      G2/M phase. From further mechanism explorations, our data showed that OPT A
      significantly upregulated the expression of a cluster of genes, especially the
      tumor necrosis factor receptor family and caspase family, suggesting that the
      tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced
      apoptosis. 

PMID- 25045938
TI  - Chicken essence improves exercise performance and ameliorates physical fatigue.
AB  - Chicken essence (CE) is a liquid nutritional supplement made from cooking whole
      chickens. In traditional Chinese medicine, CE is used to support health, promote
      healing, increase metabolism, and relieve fatigue. However, few studies have
      examined the effect of CE on exercise performance and physical fatigue. We aimed
      to evaluate the potential beneficial effects of CE on fatigue and ergogenic
      functions following physical challenge in mice. Male ICR mice were divided into
      four groups to receive vehicle or CE by oral gavage at 0, 845, 1690, or 4225
      mg/kg/day for 4 weeks. Exercise performance and anti-fatigue function were
      evaluated by forelimb grip strength, exhaustive swimming time, and levels of
      physical fatigue-related biomarkers serum lactate, ammonia, glucose, and creatine
      kinase (CK) after physical challenge. CE supplementation dose-dependently
      elevated endurance and grip strength. CE supplementation significantly decreased
      lactate, ammonia, and CK levels after physical challenge. Tissue glycogen
      content, an important energy source for exercise, was significantly increased
      with CE supplementation. In addition, CE supplementation had few subchronic toxic
      effects. The supplementation with CE can have a wide spectrum of bioactivities on
      health promotion, performance improvement and anti-fatigue. 

PMID- 25045940
TI  - Whistleblowing and the bioethicist's public obligations.
AB  - Bioethicists are sometimes thought to have heightened obligations by virtue of
      the fact that their professional role addresses ethics or morals. For this reason
      it has been argued that bioethicists ought to "whistleblow"--that is, publicly
      expose the wrongful or potentially harmful activities of their employer--more
      often than do other kinds of employees. This article argues that bioethicists do
      indeed have a heightened obligation to whistleblow, but not because bioethicists
      have heightened moral obligations in general. Rather, the special duties of
      bioethicists to act as whistleblowers are best understood by examining the nature
      of the ethical dilemma typically encountered by private employees and showing why
      bioethicists do not encounter this dilemma in the same way. Whistleblowing is
      usually understood as a moral dilemma involving conflicting duties to two
      parties: the public and a private employer. However, this article argues that
      this way of understanding whistleblowing has the implication that professions
      whose members identify their employer as the public-such as government employees
      or public servants--cannot consider whistleblowing a moral dilemma, because
      obligations are ultimately owed to only one party: the public. The article
      contends that bioethicists--even when privately employed--are similar to
      government employees in the sense that they do not have obligations to defer to
      the judgments of those with private interests. Consequently, bioethicists may be
      considered to have a special duty to whistleblow, although for different reasons
      than those usually cited.

PMID- 25045939
TI  - Nutrient intake and food habits of soccer players: analyzing the correlates of
      eating practice.
AB  - Despite the impact and popularity of soccer, and the growing field of soccer
      related scientific research, little attention has been devoted to the nutritional
      intake and eating habits of soccer players. Moreover, the few studies that have
      addressed this issue suggest that the nutritional intake of soccer players is
      inadequate, underscoring the need for better adherence to nutritional
      recommendations and the development and implementation of nutrition education
      programs. The objective of these programs would be to promote healthy eating
      habits for male and female soccer players of all ages to optimize performance and
      provide health benefits that last beyond the end of a player's career. To date,
      no well-designed nutrition education program has been implemented for soccer
      players. The design and implementation of such an intervention requires a priori
      knowledge of nutritional intake and other correlates of food selection, such as
      food preferences and the influence of field position on nutrient intake, as well
      as detailed analysis of nutritional intake on match days, on which little data is
      available. Our aim is to provide an up-to-date overview of the nutritional
      intake, eating habits, and correlates of eating practice of soccer players. 

PMID- 25045941
TI  - Assessing anti-fungal activity of isolated alveolar macrophages by confocal
      microscopy.
AB  - The lung is an interface where host cells are routinely exposed to microbes and
      microbial products. Alveolar macrophages are the first-line phagocytic cells that
      encounter inhaled fungi and other microbes. Macrophages and other immune cells
      recognize Aspergillus motifs by pathogen recognition receptors and initiate
      downstream inflammatory responses. The phagocyte NADPH oxidase generates reactive
      oxygen intermediates (ROIs) and is critical for host defense. Although NADPH
      oxidase is critical for neutrophil-mediated host defense1-3, the importance of
      NADPH oxidase in macrophages is not well defined. The goal of this study was to
      delineate the specific role of NADPH oxidase in macrophages in mediating host
      defense against A. fumigatus. We found that NADPH oxidase in alveolar macrophages
      controls the growth of phagocytosed A. fumigatus spores4. Here, we describe a
      method for assessing the ability of mouse alveolar macrophages (AMs) to control
      the growth of phagocytosed Aspergillus spores (conidia). Alveolar macrophages are
      stained in vivo and ten days later isolated from mice by bronchoalveolar lavage
      (BAL). Macrophages are plated onto glass coverslips, then seeded with green
      fluorescent protein (GFP)-expressing A. fumigatus spores. At specified times,
      cells are fixed and the number of intact macrophages with phagocytosed spores is
      assessed by confocal microscopy.

PMID- 25045942
TI  - Collection, isolation, and flow cytometric analysis of human endocervical
      samples.
AB  - Despite the public health importance of mucosal pathogens (including HIV),
      relatively little is known about mucosal immunity, particularly at the female
      genital tract (FGT). Because heterosexual transmission now represents the
      dominant mechanism of HIV transmission, and given the continual spread of
      sexually transmitted infections (STIs), it is critical to understand the
      interplay between host and pathogen at the genital mucosa. The substantial gaps
      in knowledge around FGT immunity are partially due to the difficulty in
      successfully collecting and processing mucosal samples. In order to facilitate
      studies with sufficient sample size, collection techniques must be minimally
      invasive and efficient. To this end, a protocol for the collection of cervical
      cytobrush samples and subsequent isolation of cervical mononuclear cells (CMC)
      has been optimized. Using ex vivo flow cytometry-based immunophenotyping, it is
      possible to accurately and reliably quantify CMC lymphocyte/monocyte population
      frequencies and phenotypes. This technique can be coupled with the collection of
      cervical-vaginal lavage (CVL), which contains soluble immune mediators including
      cytokines, chemokines and anti-proteases, all of which can be used to determine
      the anti- or pro-inflammatory environment in the vagina. 

PMID- 25045943
TI  - Anxiety symptomatology and perceived health in African American adults:
      moderating role of emotion regulation.
AB  - Although emotional health has been theoretically and empirically linked to
      physical health, the anxiety-physical health association in particular is not
      well understood for African American adults. This study examined anxiety as a
      specific correlate of perceived health in addition to testing the potential
      moderating role of emotion regulation, an index of how and when individuals
      modulate emotions, in the association for anxiety to perceived health. Study
      participants were 151 community-based African American adults who completed
      measures of anxiety symptomatology and emotion regulation in addition to
      responding to a self-report question of perceived health. Results showed that
      higher levels of anxiety symptomatology were associated with poorer health
      ratings for those who reported more limited access to emotion regulation
      strategies but not those who reported having more emotion regulation strategies.
      The findings suggest that anxiety-related distress and health problems may be
      interrelated when emotion regulation strategies are limited. (PsycINFO Database
      Record (c) 2014 APA, all rights reserved). 

PMID- 25045945
TI  - Predictors of self-perceived cultural competence among children's mental health
      providers.
AB  - Based on empirical research and predictions from the Multicultural Assessment
      Intervention Process model, the racial attitudes, ethnic identity, and
      acculturation of a national sample of 371 child mental health service providers
      were assessed as possible predictors of practitioner self-perceived cultural
      competence. It was hypothesized that ethnic identity and racial attitudes would
      each directly affect self-perceived cultural competence and that acculturation
      and racial attitudes would mediate the effect of ethnic identity. The results
      indicated that ethnic identity exerted a direct effect on self-perceived cultural
      competence and that this effect was partially mediated by respondents' racial
      attitudes; however, acculturation had no significant role as a mediator. The
      results are discussed within the context of the Multicultural Assessment
      Intervention Process model and implications for providing culturally competent
      services to children.

PMID- 25045944
TI  - Stereotype threat among black and white women in health care settings.
AB  - The first of its kind, the present experiment applied stereotype threat-the
      threat of being judged by or confirming negative group-based stereotypes-to the
      health sciences. Black and White women (N = 162) engaged in a virtual health care
      situation. In the experimental condition, one's ethnic identity and negative
      stereotypes of Black women specifically were made salient. As predicted, Black
      women in the stereotype threat condition who were strongly identified as Black
      (in terms of having explored what their ethnic identity means to them and the
      role it plays in their lives) reported significantly greater anxiety while
      waiting to see the doctor in the virtual health care setting than all other
      women. It is hypothesized that stereotype threat experienced in health care
      settings is one overlooked social barrier contributing to disparities in health
      care utilization and broader health disparities among Black women.

PMID- 25045947
TI  - Trends in the neuropsychological assessment of ethnic/racial minorities: a survey
      of clinical neuropsychologists in the United States and Canada.
AB  - Despite the importance of diversity variables to the clinical practice of
      neuropsychology, little is known about neuropsychologists' multicultural
      assessment practices and perspectives. The current study was the first to survey
      issues related to neuropsychologists' assessment of minority populations,
      proficiency in languages other than English, approaches to interpreting the
      cognitive scores of minorities, and perceived challenges associated with
      assessing ethnic/racial minority patients. We also surveyed respondents with
      regard to their own demographic backgrounds, as neuropsychologists who identify
      as ethnic/racial minorities are reportedly underrepresented in the field.
      Respondents were 512 (26% usable response rate; 54% female) doctorate-level
      psychologists affiliated with the International Neuropsychology Society or the
      National Academy of Neuropsychology who resided in the United States or Canada.
      Overall, results suggest that lack of appropriate norms, tests, and referral
      sources are perceived as the greatest challenges associated with assessment of
      ethnic/racial minorities, that multicultural training is not occurring for some
      practitioners, and that some are conducting assessments in foreign languages
      despite limited proficiency. In addition, ethnic/racial minorities appear to be
      grossly underrepresented in the field of neuropsychology. Findings are discussed
      in relation to the need for appropriate education and training of
      neuropsychologists in multicultural issues and the provision of more valid
      assessments for ethnic/racial minority individuals.

PMID- 25045946
TI  - How have researchers studied multiracial populations? A content and
      methodological review of 20 years of research.
AB  - The U.S. Census shows that the racial-ethnic makeup of over 9 million people
      (2.9% of the total population) who self-identified as multiracial is extremely
      diverse. Each multiracial subgroup has unique social and political histories that
      may lead to distinct societal perceptions, economic situations, and health
      outcomes. Despite the increasing academic and media interest in multiracial
      individuals, there are methodological and definitional challenges in studying the
      population, resulting in conflicting representations in the literature. This
      content and methods review of articles on multiracial populations provides a
      comprehensive understanding of which multiracial populations have been included
      in research and how they have been studied, both to recognize emerging research
      and to identify gaps for guiding future research on this complex but increasingly
      visible population. We examine 125 U.S.-based peer-reviewed journal articles
      published over the past 20 years (1990 to 2009) containing 133 separate studies
      focused on multiracial individuals, primarily from the fields of psychology,
      sociology, social work, education, and public health. Findings include (a)
      descriptive data regarding the sampling strategies, methodologies, and
      demographic characteristics of studies, including which multiracial subgroups are
      most studied, gender, age range, region of country, and socioeconomic status; (b)
      major thematic trends in research topics concerning multiracial populations; and
      (c) implications and recommendations for future studies.

PMID- 25045948
TI  - In the eyes of the beholder: National identification predicts differential
      reactions to ethnic identity expressions.
AB  - Two studies examined how perceivers' national identification influences their
      implicit and explicit attitudes toward White and non-White ethnic groups whose
      members express their ethnic identity overtly in public or discreetly in private
      spaces. Results revealed that at a conscious level, White American perceivers'
      national identification elicited more negative attitudes toward both White and
      non-White ethnic groups when members embraced their ethnic heritage in public
      rather than in private. However, at an unconscious level, White perceivers'
      identification with the national group led to less favorable attitudes toward non
      White ethnic groups, but not White ethnic groups, when their group members
      embraced ethnic identity in public. By integrating research on national
      identification, ethnic identity expression, and prejudice, the present research
      highlights some conditions under which majority group members' national
      identification affects how they perceive ethnic subgroups within the nation.

PMID- 25045949
TI  - Excluded and avoided: racial microaggressions targeting Asian international
      students in Canada.
AB  - This qualitative study explored East and South Asian international students' (N =
      12) experiences with racial microaggressions at one Canadian university. Data
      were collected through unstructured, individual interviews. Using a modified
      version of the consensual qualitative research method (Hill, Thompson, &
      Williams, 1997), we identified six racial microaggressions themes: (a) excluded
      and avoided, (b) ridiculed for accent, (c) rendered invisible, (d) disregarded
      international values and needs, (e) ascription of intelligence, and (f)
      environmental microaggressions (structural barriers on campus). In addition, we
      used the same approach to identify themes pertaining to the ways in which
      students coped with racial microaggressions: (a) engaging with own racial and
      cultural groups, (b) withdrawing from academic spheres, and (c) seeking comfort
      in the surrounding multicultural milieu. Microaggressions and coping themes
      differed based on country of origin and language proficiency. Implications for
      research and practice are discussed.

PMID- 25045951
TI  - The family-study interface and academic outcomes: differences and similarities
      between ethnic minority and ethnic majority students.
AB  - The present study investigated possible differences in the family-study interface
      between ethnic minority and ethnic majority students as an explanation for the
      poorer study results of ethnic minority students compared with those of majority
      students. We used a model for family-study conflict and facilitation derived from
      family-work and work-study models. This model held true for the full sample and
      both non-Western ethnic minority students (N = 342) and ethnic majority students
      (N = 1314) separately at a major Dutch university. Multivariate analyses of
      variance revealed that ethnic minority students reported less study effort and
      earned lower grades compared with ethnic majority students. Regarding the family
      study interface, ethnic minority students reported more family-study conflict
      than did ethnic majority students. No differences were found between the 2 groups
      in family-study facilitation. Ethnic minority students participated more in
      family activities and were more involved with their family than ethnic majority
      students. Levels of experienced family support were equal for both groups of
      students. Students who received more family social support reported less conflict
      and more facilitation. This latter finding held more strongly for majority
      students, resulting in more study effort and higher grades for this group. The
      results demonstrated the explanatory power of the family-study conflict and
      facilitation model for both groups.

PMID- 25045950
TI  - Familism, family ethnic socialization, and Mexican-origin adolescent mothers'
      educational adjustment.
AB  - The current longitudinal study examined how familism values and family ethnic
      socialization impacted Mexican-origin adolescent mothers' (N = 205) educational
      adjustment (i.e., educational expectations, educational utility), and whether
      these associations were moderated by adolescent mothers' ethnic centrality.
      Findings indicated that adolescent mothers' reports of familism values and family
      ethnic socialization were positively associated with their beliefs about
      educational utility, but not educational expectations. Ethnic centrality
      moderated the association between adolescent mothers' familism values and
      educational utility, such that adolescent mothers' endorsement of familism values
      during pregnancy were associated with significant increases in educational
      utility after their transition to parenthood, but only when adolescents reported
      high levels of ethnic centrality. Moreover, ethnic centrality was positively
      associated with adolescent mothers' educational expectations. Results highlight
      the importance of familism, ethnic socialization, and ethnic centrality for
      promoting Mexican-origin adolescent mothers' educational outcomes. Findings are
      discussed with respect to understanding adolescent mothers' educational
      adjustment in the context of family and culture.

PMID- 25045952
TI  - Giving back or giving up: Native American student experiences in science and
      engineering.
AB  - Native Americans are underrepresented in science, technology, engineering, and
      math (STEM) careers. We examine communal goal incongruence-the mismatch between
      students' emphasis on communal work goals and the noncommunal culture of STEM-as
      a possible factor in this underrepresentation. First, we surveyed 80 Native
      American STEM freshmen and found they more highly endorsed communal goals than
      individualistic work goals. Next, we surveyed 96 Native American and White
      American students in STEM and non-STEM majors and confirmed that both Native
      American men and women in STEM highly endorsed communal goals. In a third study,
      we conducted a follow-up survey and in-depth interviews with a subset of Native
      American STEM students in their second semester to assess their experiences of
      belonging uncertainty, intrinsic motivation, persistence intentions, and
      perceived performance in STEM as a function of their initial communal work goals.
      Results demonstrate the prominence of communal goals among incoming Native
      American freshman (especially compared with White male STEM majors) and the
      connection between communal goals and feelings of belonging uncertainty, low
      motivation, and perceived poor performance 1 semester later. The interview data
      illustrate that these issues are particularly salient for students raised within
      tribal communities, and that a communal goal orientation is not just a vague
      desire to "help others," but a commitment to helping their tribal communities.
      The interviews also highlight the importance of student support programs for
      fostering feelings of belonging. We end by discussing implications for
      interventions and institutional changes that may promote Native American student
      retention in STEM.

PMID- 25045953
TI  - Are the costs of neuroticism inevitable? Evidence of attenuated effects in U.S.
      Latinas.
AB  - Neuroticism is the heritable and stable personality trait defined by the tendency
      to experience negative emotion, be easily stressed, and slow to soothe.
      Neuroticism poses a risk for poor social and health outcomes that has been
      identified as a major public health concern. To date, factors that attenuate
      neuroticism's costs have not been identified. The goal of this work was to test
      the hypothesis that the costs of neuroticism would be attenuated in sociocultural
      contexts that emphasize readily accessible social support, emotional positivity,
      and physical proximity in interdependent relationships. U.S. Latino culture fits
      these characteristics. Two studies, an online survey study (Study 1) and a
      laboratory study (Study 2), tested whether three key costs of high neuroticism
      less support (Study 1), more distress (Study 2), and blunted cortisol reactivity
      (Study 2)-would be attenuated in U.S. Latinas relative to non-Latinas of European
      and East Asian cultural background. Consistent with previous research,
      neuroticism was associated with less perceived support, more distress, and
      blunted cortisol reactivity in non-Latina women of European and East Asian
      cultural background. For Latina women, however, these effects were attenuated.
      Latina women who were high in neuroticism continued to feel supported, were not
      as distressed, and their cortisol reactivity was less blunted. The role of
      sociocultural context for generating a better understanding of personality
      processes and the social malleability of neuroticism's costs are discussed.

PMID- 25045954
TI  - Income, ethnicity, and sleep: coping as a moderator.
AB  - Toward identifying variables that may protect children against sleep problems
      otherwise associated with ethnic minority status and economic adversity, support
      coping was examined as a moderator. Participants were 235 children (113 boys, 122
      girls; M age = 11.33 years, SD = 8.03 months), 64% European American and 36%
      African American. Children's sleep duration (minutes) and continuity (efficiency)
      were assessed through actigraphs worn for 1 week. Mothers reported on the
      family's monetary resources (income-to-needs ratio) and children reported on
      their support coping strategies. For children from lower income homes and African
      Americans, a higher level of support coping was a protective factor against fewer
      sleep minutes and reduced sleep efficiency, otherwise associated with economic
      adversity. Children from more economically advantaged homes had good sleep
      parameters regardless of their coping. The results build on the existing small
      body of work by demonstrating that children's support coping strategies have a
      protective role against sleep problems otherwise associated with ethnic minority
      status and economic adversity and present potential targets for intervention that
      may help reduce health disparities in an important health domain.

PMID- 25045955
TI  - Culturally adapted cognitive behavioral guided self-help for binge eating: a
      feasibility study with Mexican Americans.
AB  - Objective was to test feasibility and preliminary efficacy of a culturally
      adapted cognitive-behavioral self-help program to treat binge eating and related
      problems in Mexican Americans. Participants were 31 women recruited from the Los
      Angeles area and diagnosed with binge eating disorder, recurrent binge eating, or
      bulimia nervosa. Participants completed a culturally adapted version of a CBT
      based self-help program with 8 guidance sessions over a 3-month period. Treatment
      efficacy was evaluated in terms of binge eating, psychological functioning, and
      weight loss. Intent-to-treat analyses revealed 35.5% abstinence from binge eating
      at posttreatment and 38.7% diagnostic remission. Results indicated significant
      pretreatment to posttreatment improvement on distress level, BMI, eating disorder
      psychopathology, and self-esteem. Satisfaction with the program was high.
      Findings demonstrate that the program is acceptable, feasible, and efficacious in
      reducing binge eating and associated symptoms for Mexican American women. Study
      provides "proof of concept" for implementation of culturally adapted forms of
      evidence-based programs.

PMID- 25045956
TI  - Predicting depressive symptoms from acculturative family distancing: A study of
      Taiwanese parachute kids in adulthood.
AB  - We applied Hwang's (2006a) acculturative family distancing (AFD) theory to
      Taiwanese "parachute kids," who had immigrated to the United States or Canada as
      unaccompanied minors and remained in North American as adults. It was
      hypothesized that each dimension of AFD-communication breakdown and cultural
      value incongruence-would uniquely predict conflict with participants' family
      members in Taiwan, which would, in turn, predict their depressive symptoms. In a
      sample of 68 former parachute kids aged 18 to 36 years, the relation between
      communication breakdown and depressive symptoms was fully mediated by family
      conflict. On the other hand, the mediation effect was not found for cultural
      value incongruence. Moreover, a suppression effect occurred, suggesting the
      likelihood that an additional, unknown variable accounts for the relation between
      cultural value incongruence and depressive symptoms. We concluded, from these
      results, that the 2 AFD dimensions operate differently in this population than in
      previous AFD research. This conclusion was further supported by the finding that
      participants reported significantly more communication breakdown than cultural
      value incongruence with family members residing in Taiwan.

PMID- 25045958
TI  - Universal-diverse orientation in Asian international students: confirmatory
      factor analysis of the Miville-Guzman universality-diversity scale, short form.
AB  - Despite apparent relevance to Asian international students, universal-diverse
      orientation (UDO) has not been psychometrically validated with this population.
      The current study investigated the most researched UDO measure, the Miville
      Guzman Universality-Diversity Scale, Short Form (M-GUDS-S; Fuertes, Miville,
      Mohr, Sedlacek, & Gretchen, 2000), with 333 Asian international college students.
      The M-GUDS-S evidenced good reliability and convergent validity, and analyses
      confirmed a three-factor structure, supporting expanded use of the scale.

PMID- 25045957
TI  - The psychometric properties of the generalized anxiety disorder-7 scale in
      Hispanic Americans with English or Spanish language preference.
AB  - The Generalized Anxiety Disorder-7 scale (GAD-7) is a self-report questionnaire
      that is widely used to screen for anxiety. The GAD-7 has been translated into
      numerous languages, including Spanish. Previous studies evaluating the structural
      validity of the English and Spanish versions indicate a unidimensional factor
      structure in both languages. However, the psychometric properties of the Spanish
      language version have yet to be evaluated in samples outside of Spain, and the
      measure has not been tested for use among Hispanic Americans. This study
      evaluated the reliability, structural validity, and convergent validity of the
      English and Spanish language versions of the GAD-7 for Hispanic Americans in the
      United States. A community sample of 436 Hispanic Americans with an English (n =
      210) or Spanish (n = 226) language preference completed the GAD-7. Multiple-group
      confirmatory factor analysis (CFA) was used to examine the goodness-of-fit of the
      unidimensional factor structure of the GAD-7 across language-preference groups.
      Results from the multiple-group CFA indicated a similar unidimensional factor
      structure with equivalent response patterns and item intercepts, but different
      variances, across language-preference groups. Internal consistency was good for
      both English and Spanish language-preference groups. The GAD-7 also evidenced
      good convergent validity as demonstrated by significant correlations in expected
      directions with the Perceived Stress Scale, the Patient Health Questionnaire-9,
      and the Physical Health domain of the World Health Organization Quality of Life
      BREF assessment. The unidimensional GAD-7 is suitable for use among Hispanic
      Americans with an English or Spanish language preference.

PMID- 25045961
TI  - Mediofrontal negativity signals unexpected omission of aversive events.
AB  - Research based on event-related potential (ERP) reported mediofrontal
      negativities following unexpected negative feedback or performance error. Some
      authors proposed that these signals reflect reward prediction error for worse
      than expected outcomes, while others suggested that mediofrontal negativities
      express medial prefrontal cortex coding for unexpected non-occurrence of a
      predicted outcome, whether worse or better than expected. Many studies found
      mediofrontal negativities coding for unexpected negative outcomes; however, few
      studies found them after unexpected positive outcomes. The present study
      investigated ERP and skin conductance response (SCR) to the unexpected omission
      of electric shocks during Pavlovian aversive conditioning. To manipulate
      expectancies, participants were presented with visual stimuli paired with
      electric shock on either 80% (CS+1) or 20% (CS+2) of trials. SCR analysis
      confirmed higher shock-delivery expectancy for CS+1, relative to CS+2. ERP
      analysis evidenced a stronger negative frontocentral ERP component after
      unexpected, relative to expected, shock-omission. Methodological and theoretical
      implications are discussed. 

PMID- 25045965
TI  - California's Progress in Supporting Breastfeeding.

PMID- 25045963
TI  - Behavioral assessment of the aging mouse vestibular system.
AB  - Age related decline in balance performance is associated with deteriorating
      muscle strength, motor coordination and vestibular function. While a number of
      studies show changes in balance phenotype with age in rodents, very few isolate
      the vestibular contribution to balance under either normal conditions or during
      senescence. We use two standard behavioral tests to characterize the balance
      performance of mice at defined age points over the lifespan: the rotarod test and
      the inclined balance beam test. Importantly though, a custom built rotator is
      also used to stimulate the vestibular system of mice (without inducing overt
      signs of motion sickness). These two tests have been used to show that changes in
      vestibular mediated-balance performance are present over the murine lifespan.
      Preliminary results show that both the rotarod test and the modified balance beam
      test can be used to identify changes in balance performance during aging as an
      alternative to more difficult and invasive techniques such as vestibulo-ocular
      (VOR) measurements. 

PMID- 25045962
TI  - Excision efficiency is not strongly coupled to transgenic rate: cell type
      dependent transposition efficiency of sleeping beauty and piggyBac DNA
      transposons.
AB  - The Sleeping Beauty (SB) and piggyBac (PB) DNA transposons represent an emerging
      new gene delivery technology, potentially suitable for human gene therapy
      applications. Previous studies pointed to important differences between these
      transposon systems, depending on the cell types examined and the methodologies
      applied. However, efficiencies cannot always be compared because of differences
      in applications. In addition, "overproduction inhibition," a phenomenon believed
      to be a characteristic of DNA transposons, can remarkably reduce the overall
      transgenic rate, emphasizing the importance of transposase dose applied.
      Therefore, because of lack of comprehensive analysis, researchers are forced to
      optimize the technology for their own "in-house" platforms. In this study, we
      investigated the transposition of several SB (SB11, SB32, SB100X) and PB (mPB and
      hyPB) variants in various cell types at three levels: comparing the excision
      efficiency of the reaction by real-time PCR, testing the overall transgenic rate
      by detecting cells with stable integrations, and determining the average copy
      number when using different transposon systems and conditions. We concluded that
      high excision activity is not always followed by a higher transgenic rate, as
      exemplified by the hyperactive transposases, indicating that the excision and the
      integration steps of transposition are not strongly coupled as previously
      thought. In general, all levels of transposition show remarkable differences
      depending on the transposase used and cell lines examined, being the least
      efficient in human embryonic stem cells (hESCs). In spite of the comparably low
      activity in those special cell types, the hyperactive SB100X and hyPB systems
      could be used in hESCs with similar transgenic efficiency and with reasonably low
      (2-3) transgene copy numbers, indicating their potential applicability for gene
      therapy purposes in the future.

PMID- 25045966
TI  - Elucidation of soft tissue flap histologic margins within a canine vocal fold.
AB  - BACKGROUND: Histologic identification of implanted soft tissues in experimental
      animal models can be challenging, as donor tissue often strongly resembles the
      recipient bed. We have encountered this dilemma following implantation of a
      Composite Thyroid Ala Perichondrium flap (CTAP) into a vocal fold. The CTAP
      procedure is the first to utilize a vascularized flap for vocal fold
      reconstruction, making data to confirm or refute its viability critical. The
      current study evaluated several tissue stains to define precisely the histologic
      margins of CTAPs at two weeks post-implantation in a canine model. METHODS:
      Initial testing exposed canine cadaveric tissues to four stains (tattoo ink,
      Congo red, 4'6-diamidino-2-phenylindole, and henna) across four time periods.
      Tattoo ink alone withstood histologic processing. An exposure of 1 minute
      adequately delineated CTAP boundaries. The study concluded with a canine in vivo
      evaluation of a CTAP exposed to tattoo ink for 1 minute. After a two-week
      recovery period, vocal folds were harvested and evaluated histologically.
      RESULTS: Tattoo ink proved to be a safe and effective histologic marker in vivo,
      where the histologic margins of the implanted CTAP were clearly demarcated by a
      thin band of tattoo ink, soft tissue reactions were minimal, and interference
      with standard, special, or immunohistochemical stain assessments did not occur.
      CONCLUSIONS: Tattoo ink provides a reliable means of demarcating a CTAP within a
      vocal fold and demonstrated that CTAPs survive transplantation. Further, tattoo
      ink demarcation may serve as a useful histologic marker for those wishing to
      assess tissue implants in other in vivo models.

PMID- 25045967
TI  - Real-time ultrasonography-guided percutaneous nephrolithotomy using SonixGPS
      navigation: clinical experience and practice in a single center in China.
AB  - PURPOSE: To report our experience and evaluate the efficacy and safety of real
      time ultrasonography-guided percutaneous nephrolithotomy (PCNL) using SonixGPS
      navigation in patients with kidney stones. MATERIALS AND METHODS: From December
      2012 to May 2013 in our hospital, the SonixGPS needle tracking system was used
      for real-time ultrasonography-guided puncture during PCNL in 25 patients with
      kidney stones. All the patients were under general anesthesia, in prone position;
      holmium laser lithotripsy was used in all patients after renal access was
      established. The time needed to perform puncture and the success rate of PCNL
      were recorded as two most important outcomes of this study. RESULTS: All 25
      patients underwent PCNL successfully with the help of SonixGPS navigation. The
      mean puncture time was 5.5 minutes (range 3-9 min), and the mean operative time
      was 74 minutes (range 30-100 min), respectively. The primary stone clearance rate
      of PCNL was 92% (23/25); no major intraoperative or postoperative complications
      occurred. CONCLUSION: The results of this study indicate that puncture under
      SonixGPS navigation is safe and efficacious in PCNL, which may provides a new
      choice for PCNL.

PMID- 25045968
TI  - Improving the quality of family planning services: the role of new federal
      recommendations.
AB  - This article provides a brief overview of Federal guidelines developed by the
      Centers for Disease Control and Prevention and the United States Office of
      Population Affairs on how to deliver quality family planning services. This
      article describes how the recommendations were developed, summarizes key points,
      and outlines steps that will be taken to disseminate and increase the use of the
      recommendations by primary care providers.

PMID- 25045969
TI  - A proposal for financially sustainable population health organizations.

PMID- 25045970
TI  - The AEC/NRC 30 mCi rule: regulatory origins and clinical consequences for 131I
      remnant ablative doses.
AB  - BACKGROUND: Clinical and historical uncertainty exists surrounding the
      regulations of the Atomic Energy Commission/Nuclear Regulatory Commission
      (AEC/NRC) requiring patient hospitalization when (131)I activities exceed 30 mCi.
      This review investigates the sometimes disturbing regulatory and clinical origins
      and consequences of the use of this low, 30 mCi dose as a prescription for
      thyroid remnant ablation. SUMMARY: As early as in the 1940s, activities of (131)I
      between 30 and 200 mCi, often fractionated, were employed. The AEC deliberated
      from 1947 to the early 1960s before imposing as a license condition the
      requirement of hospitalizing patients until they contained <30 mCi of any
      byproduct material. The written AEC record throughout these years contains no
      supportive data to suggest safety issues requiring hospitalization at this
      activity level of (131)I. Yet the techniques for making the necessary
      calculations for determining radiation safety were available at this time.
      Declarations on the subject by nongovernmental bodies were misinterpreted as
      confirming such hospitalization as a legal requirement. The 30 mCi license
      condition was codified into NRC regulations in 1987 and was subsequently removed
      in 1997. Without any data, these U.S. regulatory agencies caused significant
      expense, inconvenience, and fear, affecting thyroid cancer patients and their
      families. This 30 mCi regulatory activity limit morphed, by a fortunate
      coincidence, into an acceptable ablative activity before there were solid
      confirmatory data. Studies on this 30 mCi ablative dose indicate that this
      activity was never associated with radiation health and safety issues, and was
      never more effective than higher ablative doses but led slightly more often to
      the need for a second (131)I dose. Nevertheless, the available data generally
      support the American Thyroid Association and Society of Nuclear Medicine and
      Molecular Imaging Guidelines, which indicate, without a treatment activity
      preference, that 30-100 mCi of (131)I provide adequate ablation. Follow-up data
      on the rates of recurrences, deaths, and second primary malignancies within this
      range of doses are unavailable. CONCLUSIONS: This history of unjustified
      governmental action and blind acceptance must remind the medical/radiation safety
      community to require solid data before ever again adopting baseless requirements.
      The 30 mCi dose should have never been employed as a requirement for
      hospitalization.

PMID- 25045971
TI  - A novel ERalpha-mediated reporter gene assay for screening
      estrogenic/antiestrogenic chemicals based on LLC-MK2 cells.
AB  - Low concentration of endocrine-disrupting chemicals (EDCs) may lead to serious
      consequences in animals and human, so it is essential to develop an effective
      assay for EDCs detection. In this study, we developed a novel ERalpha-mediated
      reporter gene assay based on the LLC-MK2 cells by co-transfecting pERE-sv40-Luc,
      hERalpha-pcDNA3.1, and pRL-tk. Then we determined 17beta-estradiol (E2) and some
      estrogenic/antiestrogenic chemicals to verify the validity of this assay. Data
      showed that the assay possesses a concentration-dependent responses to E2 and
      diethylstilbestrol (DES) from 10(-12 )M to 10(-8 )M with EC(50) 3.4 * 10(-10 )M
      and 5.9 * 10(-10 )M, and ICI 182,780 completely blocks the luciferase activity
      induced by 10(-9 )M E2. Bisphenol A (BPA), nonylphenol (NP), genistein (GS), and
      tamoxifen (TAM) also showed corresponding estrogenic or antiestrogenic activity
      at test concentrations. All evidences proved that the LLC-MK2 reporter gene assay
      was specific and sensitive to estrogen receptor (ER) agonistic and antagonistic
      chemicals.

PMID- 25045973
TI  - The path to healthy communities--from data to delivery.

PMID- 25045974
TI  - Global opportunities and obligations for Australian general practice.

PMID- 25045975
TI  - The end of HIV: how do we get there?

PMID- 25045978
TI  - The future of medical careers.

PMID- 25045979
TI  - Nurse practitioners in Australia: strategic errors and missed opportunities.

PMID- 25045980
TI  - Children's protective eyewear: the challenges and the way forward.

PMID- 25045981
TI  - Eye injuries and tasers.

PMID- 25045982
TI  - Severe alkali burns from beer line cleaners warrant mandatory safety guidelines.

PMID- 25045983
TI  - Linking data to improve health outcomes.

PMID- 25045984
TI  - Linking data to improve health outcomes.

PMID- 25045985
TI  - Newborn bloodspot screening: setting the Australian national policy agenda.

PMID- 25045987
TI  - Increasing incidence of Clostridium difficile infection, Australia, 2011-2012.

PMID- 25045988
TI  - Differences in chronic conditions and lifestyle behaviour between people with a
      history of cancer and matched controls.
AB  - OBJECTIVE: To determine whether people with a history of cancer have a higher
      prevalence of chronic conditions or different lifestyle behaviour compared with
      controls. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional, self-reported data
      from a telephone survey conducted between 1 January 2010 and 31 March 2012 of
      adult residents of South Australia who self-reported a previous cancer diagnosis
      (cases) and randomly selected age- and sex-matched residents with no cancer
      diagnosis (controls). MAIN OUTCOME MEASURES: Self-reported medically diagnosed
      cardiovascular disease, hypertension, hyperlipidaemia, diabetes and osteoporosis;
      lifestyle behaviour (smoking, physical activity and diet); body mass index (BMI);
      psychological distress and self-reported health. RESULTS: A total of 2103 cases
      and 4185 controls were included in the analyses. For men, after adjusting for
      age, cancer survivors were more likely than controls to have ever had
      cardiovascular disease (P<0.001), high blood pressure (P=0.001), high cholesterol
      (P<0.001) and diabetes (P=0.04). These associations remained significant after
      controlling for socioeconomic status (SES), with the exception of high blood
      pressure (P=0.09). For women, there was an increased prevalence of high
      cholesterol (P=0.005), diabetes (P=0.02) and osteoporosis (P=0.005) in cancer
      cases, but after adjusting for SES, these associations were no longer
      significant. Women with a previous cancer diagnosis were more likely than
      controls to have ever smoked, after adjusting for SES (P=0.001). There were no
      other differences in lifestyle behaviour or BMI between cases and controls for
      men or women. CONCLUSION: Despite similar lifestyle habits and BMI, the
      prevalence of chronic conditions was significantly higher among people with a
      history of cancer than among controls without cancer. This supports the
      importance of chronic disease management as part of health care after a diagnosis
      of cancer.

PMID- 25045989
TI  - Antibiotic prescribing practice in residential aged care facilities--health care
      providers' perspectives.
AB  - OBJECTIVE: To explore organisational workflow and workplace culture influencing
      antibiotic prescribing behaviour from the perspective of key health care
      providers working in residential aged care facilities (RACFs). DESIGN, SETTING
      AND PARTICIPANTS: Qualitative approach using semistructured interviews, focus
      groups and onsite observation between 8 January 2013 and 2 July 2013. Nursing
      staff, general practitioners and pharmacists servicing residents at 12 high-level
      care RACFs in Victoria were recruited. MAIN OUTCOME MEASURES: Emergent themes on
      antibiotic prescribing practices in RACFs. RESULTS: Sixty-one participants (40
      nurses, 15 GPs and six pharmacists) participated. Factors influencing antibiotic
      prescribing practice have been divided into workflow-related and culture-related
      factors. Five major themes emerged among workflow-related factors: logistical
      challenges with provision of medical care, pharmacy support, nurse-driven
      infection management, institutional policies and guidelines, and external
      expertise and diagnostic facilities. Lack of onsite medical and pharmacy staff
      led to nursing staff adopting significant roles in infection management. However,
      numerous barriers hindered optimal antibiotic prescribing, especially
      inexperienced staff, lack of training of nurses in antibiotic use and lack of
      institutional infection management guidelines. With regard to culture-related
      factors, pressure from family to prescribe and institutional use of advance care
      directives were identified as important influences on antibiotic prescribing
      practices. CONCLUSIONS: Workflow- and culture-related barriers to optimal
      antibiotic prescribing were identified. This study has provided important
      insights to guide antimicrobial stewardship interventions in the RACF setting,
      particularly highlighting the role of nurses.

PMID- 25045990
TI  - A short-term rural placement can change metropolitan medical students' knowledge
      of, and attitudes to, rural practice.
AB  - OBJECTIVE: To determine whether a short-term placement of metropolitan medical
      students in a rural environment can improve their knowledge of, and change their
      attitudes to, rural health issues. DESIGN AND PARTICIPANTS: Medical students
      taking part in the March and May 2013 3-week Rural Health Modules (RHMs) were
      invited to participate in focus groups and complete questionnaires before
      undertaking the RHM, after a 2-day rural orientation and at the end of the RHM.
      Students were asked to comment on a range of issues affecting rural health care
      including their attitude to pursuing a rural career. Focus group transcripts were
      thematically analysed and questionnaire data were statistically analysed.
      SETTING: The RHM is a 3-week program designed and run by the University of
      Melbourne's Rural Health Academic Centre. MAIN OUTCOME MEASURES: Responses to
      questionnaire items from before and after completing the RHM, scored on a seven
      point Likert scale. RESULTS: 69 of the 101 RHM students took part in this study.
      The focus groups identified five main themes in rural health care: access;
      teamwork, models of care and generalist practice; overlapping relationships;
      indigenous health; and working in a rural career. In all five areas, a change was
      seen in the depth of knowledge students had about these issues and in the
      students' attitudes towards rural health care. The questionnaires also showed a
      significant shift in the students' appreciation of, and positivity towards, rural
      health issues. CONCLUSION: Undertaking a 3-week RHM changed students' perceptions
      of rural health and significantly improved their knowledge of issues facing rural
      health practitioners and patients.

PMID- 25045991
TI  - Influenza vaccine effectiveness in Australia: results from the Australian
      Sentinel Practices Research Network.
AB  - OBJECTIVE: To estimate influenza vaccine coverage and effectiveness against
      medically attended laboratory-confirmed influenza for the 2012 season. DESIGN,
      SETTING AND PARTICIPANTS: Test-negative design involving patients recruited as
      part of the Australian Sentinel Practices Research Network, a network of sentinel
      general practitioners throughout Australia. Throughout 2012, at the discretion of
      the GP at one of 102 participating practices, patients presenting with influenza
      like illness were swabbed and included in the study. MAIN OUTCOME MEASURE:
      Influenza vaccine effectiveness (VE) estimated as (1-OR)*100% by logistic
      regression. RESULTS: 1775 patients were swabbed. The epidemic period was
      identified as Weeks 10 to 43 of 2012. After exclusions, there were 1414 patients
      for the VE analysis, including 593 (42%) who tested influenza-positive and 821
      who tested negative. 27% of test-negative patients were vaccinated, of whom most
      were aged 50 years and over. The overall VE, adjusted for age group, month of
      presentation and state or territory, was 23% (95% CI, -4% to 43%) against all
      influenza types, 15% (95% CI, -17% to 38%) against influenza A, 13% (95% CI, -20%
      to 36%) against influenza A(not H1) and 53% (95% CI, 5% to 77%) against influenza
      B. CONCLUSION: Vaccination against influenza was modestly protective, reducing
      the risk of medical presentation with influenza by around 23%.

PMID- 25045992
TI  - Severe bilateral Pseudomonas keratitis exacerbated by prolonged contact lens
      wear.

PMID- 25045993
TI  - Black bones: minocycline-induced bone pigmentation.

PMID- 25045994
TI  - Dysphagia, regurgitation and weight loss in an elderly man.

PMID- 25045995
TI  - True to label. 1937.

PMID- 25045997
TI  - Challenges and emerging solutions in the development of compressed orally
      disintegrating tablets.
AB  - INTRODUCTION: Orally disintegrating tablets (ODTs) provide several advantages
      over conventional tablets such as suitability for patients with swallowing
      difficulties and faster onset of action. The manufacture of ODTs by
      compression/tableting offers a practical and cost-effective strategy over the
      freeze drying (lyophilisation) method. Nonetheless, the FDA recommends a
      disintegration time of 30 s and a maximum weight of 500 mg for a tablet to be
      labelled as an ODT. These requirements, alongside other desirable product
      properties, have created a number of challenges for the formulator to overcome
      while developing compressed ODTs. AREAS COVERED: The review discusses the main
      challenges of ODT manufacturing process and the emerging solutions featured at
      early drug development stages. The research specifically describes the methods
      reported for taste masking/assessment and solubilisation of unpalatable and
      poorly soluble drugs, respectively. Furthermore, this review highlights the
      techniques used for developing modified-release ODTs, an emerging area in the
      field. In addition, it also discusses the poor flowability and segregation
      problems of directly compressed powders. Moreover, the review describes the tests
      reported in the literature for ODT disintegration time assessment since a
      universal technique is still non-existent. EXPERT OPINION: The approaches used to
      overcome the manufacturing challenges often have a bearing on the price of the
      end product. However, despite the technical and regulatory challenges, ODTs can
      offer many advantages over the conventional dosage forms if accompanied by
      suitable adjuvant technologies and in vitro analytical tools.

PMID- 25045996
TI  - Oral pre-exposure prophylaxis (PrEP) for prevention of HIV in serodiscordant
      heterosexual couples in the United States: opportunities and challenges.
AB  - Oral HIV pre-exposure prophylaxis (PrEP) is a promising new biomedical prevention
      approach in which HIV-negative individuals are provided with daily oral
      antiretroviral medication for the primary prevention of HIV-1. Several clinical
      trials have demonstrated efficacy of oral PrEP for HIV prevention among groups at
      high risk for HIV, with adherence closely associated with level of risk
      reduction. In the United States (US), three groups have been prioritized for
      initial implementation of PrEP-injection drug users, men who have sex with men at
      substantial risk for HIV, and HIV-negative partners within serodiscordant
      heterosexual couples. Numerous demonstration projects involving PrEP
      implementation among MSM are underway, but relatively little research has been
      devoted to study PrEP implementation in HIV-serodiscordant heterosexual couples
      in the US. Such couples face a unique set of challenges to PrEP implementation at
      the individual, couple, and provider level with regard to PrEP uptake and
      maintenance, adherence, safety and toxicity, clinical monitoring, and sexual risk
      behavior. Oral PrEP also provides new opportunities for serodiscordant couples
      and healthcare providers for primary prevention and reproductive health. This
      article provides a review of the critical issues, challenges, and opportunities
      involved in the implementation of oral PrEP among HIV-serodiscordant heterosexual
      couples in the US.

PMID- 25045999
TI  - Role of GM-CSF in the inflammatory cytokine network that regulates neutrophil
      influx into the colonic mucosa during Clostridium difficile infection in mice.
AB  - Clostridium difficile infection in antibiotic-treated mice results in acute
      colitis characterized by severe intestinal histopathology, robust neutrophil
      influx, and increased expression of numerous inflammatory cytokines, including GM
      CSF. We utilized a neutralizing monoclonal antibody (mAb) against GM-CSF in a
      murine model to study the role of GM-CSF during acute C. difficile colitis.
      Cefoperazone-treated mice were challenged with C. difficile (strain 630) spores.
      Expression of GM-CSF was significantly increased in animals challenged with C.
      difficile. Treatment with an anti-GM-CSF mAb did not alter C. difficile
      colonization levels, weight loss, or expression of IL-22 and RegIIIgamma.
      However, expression of the inflammatory cytokines TNFalpha and IL-1beta, as well
      as iNOS, was significantly reduced following anti-GM-CSF treatment. Expression of
      the neutrophil chemokines CXCL1 and CXCL2, but not the chemokines CCL2, CCL4,
      CXCL9, and CXCL10, was significantly reduced by anti-GM-CSF treatment. Consistent
      with a decrease in neutrophil-attractant chemokine expression, there were fewer
      neutrophils in histology sections and a reduction in the expression of secretory
      leukocyte protease inhibitor (SLPI), a tissue anti-protease that protects against
      damage by secreted neutrophil elastase. These data indicate that GM-CSF plays a
      role in the inflammatory signaling network that drives neutrophil recruitment in
      response to C. difficile infection but does not appear to play a role in
      clearance of the infection. 

PMID- 25046002
TI  - Synthesis of aza-fused isoquinolines through domino cross-aldol condensation and
      palladium-catalyzed intramolecular direct arylation.
AB  - A straightforward method has been developed for the synthesis of aroyl
      substituted imidazo-/benzimidazo-fused isoquinolines. The cascade reaction
      proceeds via a cross-aldol condensation of 2-(1H-imidazol-1-yl/benzimidazolyl-1
      yl)-1-arylethanones and 2-bromobenzaldehyde followed by palladium-catalyzed
      intramolecular C-H functionalization. This approach offers a simple and efficient
      alternative one-pot protocol for the assembly of imidazo/benzimidazo[2,1
      a]isoquinolines in moderate to good yields. 

PMID- 25046000
TI  - Production of IL-1beta by bone marrow-derived macrophages in response to
      chemotherapeutic drugs: synergistic effects of doxorubicin and vincristine.
AB  - Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely
      employed to treat a variety of cancers in patients but often lead to serious
      symptoms that negatively affect physical functioning and quality of life. There
      is compelling evidence that implicates cytotoxic chemotherapy-induced
      inflammation in the etiology of these symptoms. Because IL-1beta plays a central
      role as an initiator cytokine in immune responses, we compared doxorubicin, a
      drug known to induce IL-1beta production, with ten other commonly prescribed
      chemotherapeutic drugs in their ability to lead to processing and secretion of IL
      1beta by primary mouse macrophages. Seven of them (melphalan, cisplatin,
      vincristine, etoposide, paclitaxel, methotrexate, and cytarabine) caused the
      production of IL-1beta in cells pretreated with lipopolysaccharide. When
      delivered in combination with doxorubicin, one of the drugs, vincristine, was
      also capable of synergistically activating the NLRP3-dependent inflammasome and
      increasing expression of IL-1beta, IL-6, and CXCL1. The absence of TNF-alpha and
      IL-1 signaling caused a partial reduction in the production of mature IL-1beta.
      Three small-molecule inhibitors known to suppress activity of kinases situated
      upstream of mitogen-activated kinases (MAPKs) inhibited the expression of IL
      1beta, IL-6, and CXCL1 when doxorubicin and vincristine were used singly or
      together, so specific kinase inhibitors may be useful in reducing inflammation in
      patients receiving chemotherapy. 

PMID- 25046001
TI  - Toward "stable-on-the-table" enzymes: improving key properties of catalase by
      covalent conjugation with poly(acrylic acid).
AB  - Several key properties of catalase such as thermal stability, resistance to
      protease degradation, and resistance to ascorbate inhibition were improved, while
      retaining its structure and activity, by conjugation to poly(acrylic acid) (PAA,
      Mw 8000) via carbodiimide chemistry where the amine groups on the protein are
      appended to the carboxyl groups of the polymer. Catalase conjugation was examined
      at three different pH values (pH 5.0, 6.0, and 7.0) and at three distinct mole
      ratios (1:100, 1:500, and 1:1000) of catalase to PAA at each reaction pH. The
      corresponding products are labeled as Cat-PAA(x)-y, where x is the protein to
      polymer mole ratio and y is the pH used for the synthesis. The coupling reaction
      consumed about 60-70% of the primary amines on the catalase; all samples were
      completely water-soluble and formed nanogels, as evidenced by gel electrophoresis
      and electron microscopy. The UV circular dichroism (CD) spectra indicated
      substantial retention of protein secondary structure for all samples, which
      increased to 100% with increasing pH of the synthesis and polymer mole fraction.
      Soret CD bands of all samples indicated loss of ~50% of band intensities,
      independent of the reaction pH. Catalytic activities of the conjugates increased
      with increasing synthesis pH, where 55-80% and 90-100% activity was retained for
      all samples synthesized at pH 5.0 and pH 7.0, respectively, and the Km or Vmax
      values of Cat-PAA(100)-7 did not differ significantly from those of the free
      enzyme. All conjugates synthesized at pH 7.0 were thermally stable even when
      heated to ~85-90  degrees C, while native catalase denatured between 55 and 65 
      degrees C. All conjugates retained 40-90% of their original activities even after
      storing for 10 weeks at 8  degrees C, while unmodified catalase lost all of its
      activity within 2 weeks, under similar storage conditions. Interestingly, PAA
      surrounding catalase limited access to the enzyme from large molecules like
      proteases and significantly increased resistance to trypsin digestion compared to
      unmodified catalase. Similarly, negatively charged PAA surrounding the catalase
      in these conjugates protected the enzyme against inhibition by negatively charged
      inhibitors such as ascorbate. While Cat-PAA(100)-7 did not show any inhibition by
      ascorbate in the presence of 270 MUM ascorbate, unmodified catalase lost ~70% of
      its activity under similar conditions. This simple, facile, and rational
      methodology produced thermostable, storable catalase that is also protected from
      protease digestion and ascorbate inhibition and most likely prevented the
      dissociation of the multimer. Using synthetic polymers to protect and improve
      enzyme properties could be an attractive approach for making "Stable-on-the
      Table" enzymes, as a viable alternative to protein engineering. 

PMID- 25046003
TI  - Improving lipid control following myocardial infarction.
AB  - PURPOSE OF REVIEW: Following a myocardial infarction, lipid-lowering therapy is
      an established intervention to reduce the risk of recurrent cardiovascular
      events. Prior studies show a need to improve clinical practice in this area.
      Here, we review the latest research and perspectives on improving postmyocardial
      infarction lipid control. RECENT FINDINGS: Dyslipidemia and myocardial infarction
      remain leading causes of global disability and premature mortality throughout the
      world. The processes of care in lipid control involve multiple patient-level,
      provider-level, and healthcare system-level factors. They can be challenging to
      coordinate. Recent studies show suboptimal use of early high-intensity statin
      therapy and overall lipid control following myocardial infarction. Encouragingly,
      lipid control has improved over the last decade. Implementation science has
      identified checklists as an effective tool. At the top of the checklist for
      reducing atherogenic lipids and recurrent event risk postmyocardial infarction is
      early high-intensity statin therapy. Smoking cessation and participation in
      cardiac rehabilitation are also priorities, as are lifestyle counseling,
      promotion of medication adherence, ongoing lipid surveillance, and medication
      management. SUMMARY: Optimizing lipid control could further enhance clinical
      outcomes after myocardial infarction.

PMID- 25046004
TI  - Recent developments in echocardiographic imaging.
AB  - PURPOSE OF REVIEW: This review provides an outline of recent applications related
      to the use of ultrasonography in various catheter-based procedures for the repair
      of many valvular abnormalities. RECENT FINDINGS: Percutaneous interventions are
      becoming a safe and effective therapeutic modality in the management of various
      valvular defects. The intrinsic ability of ultrasound to provide real-time
      accurate assessment of cardiac and valvular structural and functional
      abnormalities makes this modality distinctively useful in the execution of
      percutaneous valvular procedures and evaluation of their results.Clinical
      applications of myocardial deformation and cardiac mechanics have been
      investigated in an increasing number of clinical applications. Speckle tracking
      accurately measures myocardial deformation parameters and has been recently
      applied to the evaluation of mitral insufficiency mechanisms. SUMMARY: Recent
      developments in echocardiography are promoting this modality from its traditional
      role of diagnostic technique into one suitable for aiding in the execution of
      complex catheter-based procedures and for accurate monitoring of therapeutic
      response in many clinical settings.

PMID- 25046006
TI  - Ultrananocrystalline diamond-decorated silicon nanowire field emitters.
AB  - Silicon nanowires (SiNWs) were uniformly decorated with ultrananocrystalline
      diamond (UNCD) by a novel route using paraffin wax as the seeding source, which
      is more efficient in the creation of diamond nuclei than traditional methods.
      These one-dimensional ultrananocrystalline diamond-decorated SiNWs (UNCD/SiNWs)
      exhibit uniform diameters ranging from 100 to 200 nm with a bulbous catalytic tip
      of ~250 nm in diameter and an UNCD grain size of ~5 nm. UNCD/SiNW nanostructures
      demonstrated enhanced electron field emission (EFE) properties with a turn-on
      field of about 3.7 V/MUm. Current densities around 2 mA/cm(2) were achieved at 25
      V/MUm, which is significantly enhanced as compared to bare SiNWs. 

PMID- 25046007
TI  - Timing, frequency and type of physician-diagnosed infections in childhood and
      risk for Crohn's disease in children and young adults.
AB  - BACKGROUND: Recent experimental data show that exposure to microbes during early
      childhood can confer immunological tolerance and protect against Crohn's disease
      (CD). Epidemiological evidence for this link, however, remains controversial.
      Using prospective data, we examined the link between this hypothesis and risk for
      CD in children and young adults. METHODS: A case-control study design was used.
      CD cases (diagnosed before age 20 years) were recruited from a tertiary-care
      pediatric hospital in Montreal, and population-based controls matched for age,
      gender and, geographical location were selected. Infection data were ascertained
      from physician-billing records. These records, which use International
      Classification of Diseases, Ninth Revision diagnostic codes, were consulted
      retrospectively but provide prospectively collected diagnostic information.
      Conditional logistic regression analysis was used to study potential
      associations. Odds ratios (OR) and 95% confidence intervals (95% CI) were
      estimated. RESULTS: Four hundred nine cases and 1621 controls were included.
      Regression analysis adjusting for potential confounding variables suggested that
      any recorded infection before the diagnosis of CD was associated with reduced
      risk of CD (OR, 0.67; 95% CI, 0.48-0.93). The protective effect was restricted to
      infections occurring mainly before 5 years of age, with increasing number of
      infections resulting in greater protection (1-5 infections: OR, 0.74; >=6
      infections: OR, 0.61; P value for trend = 0.039). Infections affecting the oral
      and upper respiratory tracts, cellulitis, and, enteric infections seemed most
      protective. CONCLUSIONS: Our study provides support for the hygiene hypothesis,
      whereby exposure to infections in early childhood could potentially reduce risks
      of CD.

PMID- 25046008
TI  - Long-term comparative efficacy of cyclosporine- or infliximab-based strategies
      for the management of steroid-refractory ulcerative colitis attacks.
AB  - BACKGROUND: The short-term efficacy of infliximab (IFX) and cyclosporine A (CsA)
      in steroid-refractory ulcerative colitis (SRUC) has been recently shown to be
      similar, but long-term outcomes are still unclear. Moreover, the need for further
      rescue therapies in patients treated with IFX or CsA for SRUC has not been
      reported. The aims of our study were to compare short-term and long-term efficacy
      between 2 different strategies based on initial treatment with CsA or IFX for
      SRUC attacks. PATIENTS AND METHODS: Between January 2005 and December 2011, all
      patients admitted for SRUC who required medical rescue therapy were identified
      from the electronic databases of 3 referral centers and grouped according to
      whether they received CsA or IFX as first-line rescue therapy, and
      retrospectively reviewed. RESULTS: Among 50 SRUC attacks, 20 were treated with
      CsA as first-line rescue therapy and 30 with IFX. The CsA group had a higher
      proportion of patients with severe UC activity immediately before rescue therapy
      (P = 0.03) and a shorter median time from intravenous corticosteroids to rescue
      therapy (P = 0.03). A higher proportion of patients in the CsA group received
      second-line drug therapy (switch) as compared with the IFX group (P = 0.04).
      Fifteen patients (30%) were colectomized during the study period, with no between
      group differences. Previous thiopurine exposure (P = 0.004; odds ratio = 6.1 [1.7
      20.9]) was the only independent predictor of colectomy. CONCLUSIONS: CsA- and IFX
      based strategies for SRUC seem similarly effective in preventing colectomy in the
      short and long term, although second-line drug therapy is more often required
      with CsA-based strategies.

PMID- 25046009
TI  - Role of intestinal bacteria in the pathogenesis of pouchitis.
AB  - Pouchitis is a common complication seen in patients with ulcerative colitis who
      undergo total proctocolectomy with ileal pouch anal anastomosis. Bacteria seem to
      play an important role in the development of pouchitis, although this role is not
      well defined. Because technology has advanced, we are able to apply molecular
      techniques to describe the structure and function of the pouch microbial
      community. In recent years, several studies have been performed comparing the
      pouch microbiota in patients with ulcerative colitis with healthy pouches and
      pouchitis. Many of these studies have suggested that pouchitis is characterized
      by dysbiosis and/or decreased microbial diversity. There has not been a clear
      pattern identifying a pathogenic organism or a group of organisms responsible for
      pouchitis. This review summarizes recent studies exploring the pouch microbiota
      in health and disease, the relationship of bacterial metabolites and pouchitis,
      and the role of antibiotics and probiotics for the treatment and prevention of
      pouchitis.

PMID- 25046010
TI  - A self-referencing intensity-based fiber optic sensor with multipoint sensing
      characteristics.
AB  - A self-referencing, intensity-based fiber optic sensor (FOS) is proposed and
      demonstrated. The theoretical analysis for the proposed design is given, and the
      validity of the theoretical analysis is confirmed via experiments. We define the
      measurement parameter, X, and the calibration factor, beta, to find the transfer
      function, , of the intensity-based FOS head. The self-referencing and multipoint
      sensing characteristics of the proposed system are validated by showing the
      measured and relative error versus the optical power attenuation of the sensor
      head for four cases: optical source fluctuation, various remote sensing point
      distances, fiber Bragg gratings (FBGs) with different characteristics, and
      multiple sensor heads with cascade and/or parallel forms. The power-budget
      analysis and limitations of the measurement rates are discussed, and the
      measurement results of fiber-reinforced plastic (FRP) coupon strain using the
      proposed FOS are given as an actual measurement. The proposed FOS has several
      benefits, including a self-referencing characteristic, the flexibility to
      determine FBGs, and a simple structure in terms of the number of devices and
      measuring procedure.

PMID- 25046011
TI  - A novel crosstalk suppression method of the 2-D networked resistive sensor array.
AB  - The 2-D resistive sensor array in the row-column fashion suffered from the
      crosstalk problem for parasitic parallel paths. Firstly, we proposed an Improved
      Isolated Drive Feedback Circuit with Compensation (IIDFCC) based on the voltage
      feedback method to suppress the crosstalk. In this method, a compensated resistor
      was specially used to reduce the crosstalk caused by the column multiplexer
      resistors and the adjacent row elements. Then, a mathematical equivalent
      resistance expression of the element being tested (EBT) of this circuit was
      analytically derived and verified by the circuit simulations. The simulation
      results show that the measurement method can greatly reduce the influence on the
      EBT caused by parasitic parallel paths for the multiplexers' channel resistor and
      the adjacent elements. 

PMID- 25046012
TI  - Introduction and testing of a monitoring and colony-mapping method for waterbird
      populations that uses high-speed and ultra-detailed aerial remote sensing.
AB  - Remote sensing is a method that collects data of the Earth's surface without
      causing disturbances. Thus, it is worthwhile to use remote sensing methods to
      survey endangered ecosystems, as the studied species will behave naturally while
      undisturbed. The latest passive optical remote sensing solutions permit surveys
      from long distances. State-of-the-art highly sensitive sensor systems allow high
      spatial resolution image acquisition at high altitudes and at high flying speeds,
      even in low-visibility conditions. As the aerial imagery captured by an airplane
      covers the entire study area, all the animals present in that area can be
      recorded. A population assessment is conducted by visual interpretations of an
      ortho image map. The basic objective of this study is to determine whether small-
      and medium-sized bird species are recognizable in the ortho images by using high
      spatial resolution aerial cameras. The spatial resolution needed for identifying
      the bird species in the ortho image map was studied. The survey was adjusted to
      determine the number of birds in a colony at a given time. 

PMID- 25046013
TI  - Dry EEG electrodes.
AB  - Electroencephalography (EEG) emerged in the second decade of the 20th century as
      a technique for recording the neurophysiological response. Since then, there has
      been little variation in the physical principles that sustain the signal
      acquisition probes, otherwise called electrodes. Currently, new advances in
      technology have brought new unexpected fields of applications apart from the
      clinical, for which new aspects such as usability and gel-free operation are
      first order priorities. Thanks to new advances in materials and integrated
      electronic systems technologies, a new generation of dry electrodes has been
      developed to fulfill the need. In this manuscript, we review current approaches
      to develop dry EEG electrodes for clinical and other applications, including
      information about measurement methods and evaluation reports. We conclude that,
      although a broad and non-homogeneous diversity of approaches has been evaluated
      without a consensus in procedures and methodology, their performances are not far
      from those obtained with wet electrodes, which are considered the gold standard,
      thus enabling the former to be a useful tool in a variety of novel applications. 

PMID- 25046014
TI  - Lamb wave line sensing for crack detection in a welded stiffener.
AB  - This paper proposes a novel Lamb wave line sensing technique for crack detection
      in a welded stiffener. The proposed technique overcomes one of the biggest
      technical challenges of Lamb wave crack detection for real structure
      applications: crack-induced Lamb waves are often mixed with multiple reflections
      from complex waveguides. In particular, crack detection in a welded joint, one of
      the structural hot spots due to stress concentration, is accompanied by
      reflections from the welded joint as well as a crack. Extracting and highlighting
      crack-induced Lamb wave modes from Lamb wave responses measured at multi-spatial
      points along a single line can be accomplished through a frequency-wavenumber
      domain analysis. The advantages of the proposed technique enable us not only to
      enhance the crack detectability in the welded joint but also to minimize false
      alarms caused by environmental and operational variations by avoiding the direct
      comparison with the baseline data previously accumulated from the pristine
      condition of a target structure. The proposed technique is experimentally and
      numerically validated in vertically stiffened metallic structures, revealing that
      it successfully identifies and localizes subsurface cracks, regardless of the
      coexistence with the vertical stiffener. 

PMID- 25046015
TI  - Modeling and analysis of a microresonating biosensor for detection of Salmonella
      bacteria in human blood.
AB  - A new photonics biosensor configuration comprising a Double-side Ring Add-drop
      Filter microring resonator (DR-ADF) made from SiO2-TiO2 material is proposed for
      the detection of Salmonella bacteria (SB) in blood. The scattering matrix method
      using inductive calculation is used to determine the output signal's intensities
      in the blood with and without presence of Salmonella. The change in refractive
      index due to the reaction of Salmonella bacteria with its applied antibody on the
      flagellin layer loaded on the sensing and detecting microresonator causes the
      increase in through and dropper port's intensities of the output signal which
      leads to the detection of SB in blood. A shift in the output signal wavelength is
      observed with resolution of 0.01 nm. The change in intensity and shift in
      wavelength is analyzed with respect to the change in the refractive index which
      contributes toward achieving an ultra-high sensitivity of 95,500 nm/RIU which is
      almost two orders higher than that of reported from single ring sensors and the
      limit of detection is in the order of 1 * 10(-8) RIU. In applications, such a
      system can be employed for a high sensitive and fast detection of bacteria.

PMID- 25046016
TI  - Automatic fall monitoring: a review.
AB  - Falls and fall-related injuries are major incidents, especially for elderly
      people, which often mark the onset of major deterioration of health. More than
      one-third of home-dwelling people aged 65 or above and two-thirds of those in
      residential care fall once or more each year. Reliable fall detection, as well as
      prevention, is an important research topic for monitoring elderly living alone in
      residential or hospital units. The aim of this study is to review the existing
      fall detection systems and some of the key research challenges faced by the
      research community in this field. We categorize the existing platforms into two
      groups: wearable and ambient devices; the classification methods are divided into
      rule-based and machine learning techniques. The relative merit and potential
      drawbacks are discussed, and we also outline some of the outstanding research
      challenges that emerging new platforms need to address. 

PMID- 25046017
TI  - Association rule extraction from XML stream data for wireless sensor networks.
AB  - With the advances of wireless sensor networks, they yield massive volumes of
      disparate, dynamic and geographically-distributed and heterogeneous data. The
      data mining community has attempted to extract knowledge from the huge amount of
      data that they generate. However, previous mining work in WSNs has focused on
      supporting simple relational data structures, like one table per network, while
      there is a need for more complex data structures. This deficiency motivates XML,
      which is the current de facto format for the data exchange and modeling of a wide
      variety of data sources over the web, to be used in WSNs in order to encourage
      the interchangeability of heterogeneous types of sensors and systems. However,
      mining XML data for WSNs has two challenging issues: one is the endless data
      flow; and the other is the complex tree structure. In this paper, we present
      several new definitions and techniques related to association rule mining over
      XML data streams in WSNs. To the best of our knowledge, this work provides the
      first approach to mining XML stream data that generates frequent tree items
      without any redundancy. 

PMID- 25046018
TI  - Short chain N-acyl homoserine lactone production in tropical marine Vibrio
      sinaloensis strain T47.
AB  - Quorum sensing (QS), acts as one of the gene regulatory systems that allow
      bacteria to regulate their physiological activities by sensing the population
      density with synchronization of the signaling molecules that they produce. Here,
      we report a marine isolate, namely strain T47, and its unique AHL profile. Strain
      T47 was identified using 16S rRNA sequence analysis confirming that it is a
      member of Vibrio closely clustered to Vibrio sinaloensis. The isolated V.
      sinaloensis strain T47 was confirmed to produce N-butanoyl-L-homoserine lactone
      (C4-HSL) by using high resolution liquid chromatography tandem mass spectrometry.
      V. sinaloensis strain T47 also formed biofilms and its biofilm formation could be
      affected by anti-QS compound (cathechin) suggesting this is a QS-regulated trait
      in V. sinaloensis strain T47. To our knowledge, this is the first documentation
      of AHL and biofilm production in V. sinaloensis strain T47. 

PMID- 25046019
TI  - Improved artificial bee colony algorithm based gravity matching navigation
      method.
AB  - Gravity matching navigation algorithm is one of the key technologies for gravity
      aided inertial navigation systems. With the development of intelligent
      algorithms, the powerful search ability of the Artificial Bee Colony (ABC)
      algorithm makes it possible to be applied to the gravity matching navigation
      field. However, existing search mechanisms of basic ABC algorithms cannot meet
      the need for high accuracy in gravity aided navigation. Firstly, proper
      modifications are proposed to improve the performance of the basic ABC algorithm.
      Secondly, a new search mechanism is presented in this paper which is based on an
      improved ABC algorithm using external speed information. At last, modified
      Hausdorff distance is introduced to screen the possible matching results. Both
      simulations and ocean experiments verify the feasibility of the method, and
      results show that the matching rate of the method is high enough to obtain a
      precise matching position. 

PMID- 25046020
TI  - A time-independent free energy estimator for metadynamics.
AB  - Metadynamics is a powerful and well-established enhanced sampling method for
      exploring and quantifying free energy surfaces of complex systems as a function
      of appropriately chosen variables. In the limit of long simulation time,
      metadynamics converges to the exact free energy surface plus a time-dependent
      constant. In this article, we analyze in detail this time-dependent constant. We
      show an easy way to calculate it, and by explicitly calculating the time
      dependence of this constant, we are able to derive a time-independent and locally
      convergent free energy estimator for metadynamics. We also derive an alternate
      procedure for obtaining the full unbiased distributions of generic operators from
      biased metadynamics simulations and explicitly test its usefulness. 

PMID- 25046021
TI  - A preliminary controlled trial of a trans-diagnostic programme for cognitive
      behaviour therapy with adults with intellectual disability.
AB  - BACKGROUND: Several studies have found a heightened prevalence of mental health
      disorders in people with intellectual disabilities (ID). There have been a number
      of successful case series and two promising controlled treatment trials of
      cognitive behaviour therapy (CBT) for emotional disorders (excluding anger) for
      people with ID. Several authors have promoted the development of trans-diagnostic
      approaches to cognitive treatment. The present study extends this work with the
      development and evaluation of a trans-diagnostic treatment manual for CBT in
      people with ID. METHOD: A controlled treatment trial was conducted with 12
      participants in treatment and waiting list control data. Each treatment
      participant was matched to a control on age, IQ, presenting problem, and Brief
      Symptom Inventory (BSI) global severity index (GSI) score. The treatment group
      was also evaluated on the Glasgow anxiety and depression scales and was followed
      up for 3 to 6 months after treatment. RESULTS: There were no significant
      differences between groups at baseline. Following treatment, the CBT group was
      significantly improved when compared with the control group on the GSI scale of
      the BSI. The ancovas for all other measures were not significant but there were
      significant improvements for the treatment group on all scaled except BSI
      depression from pre to post-CBT. Gains were maintained to follow up, and changes
      were associated with large effect sizes. CONCLUSIONS: It was possible to treat a
      range of symptoms and psychiatric diagnoses with a general trans-diagnostic CBT
      manual. The effects of therapy were promising, suggesting that the participants
      could respond to treatment in a meaningful and helpful manner and supporting the
      case for further evaluation of the trans-diagnostic approach in ID.

PMID- 25046022
TI  - Photo-induced proton-coupled electron transfer reactions of acridine orange:
      comprehensive spectral and kinetics analysis.
AB  - The triplet excited state of acridine orange ((3)*AO) undergoes a proton-coupled
      electron transfer (PCET) reaction with tri-tert-butylphenol ((ttb)PhOH) in
      acetonitrile. Each of the reaction components possesses a spectroscopic
      signature, providing a rare opportunity to monitor the individual proton
      transfer, electron transfer, and H(*)-transfer components in parallel via
      transient absorption spectroscopy. This enhanced optical tracking, along with
      excited-state thermochemical analysis, facilitates assignment of the mechanism of
      excited-state PCET reactivity. (3)*AO is quenched via concerted proton-electron
      transfer (CPET) from (ttb)PhOH to form acridine radical (AOH(*)) and (ttb)PhO(*)
      (kCPET = 3.7 * 10(8) M(-1) s(-1), KIE = 1.3). Subsequently, AOH(*) reduces the
      phenoxyl radical (kET = 5.5 * 10(9) M(-1) s(-1)), forming AOH(+) and (ttb)PhO(-),
      followed by proton transfer (kPT = 1.0 * 10(9) M(-1) s(-1)) to regenerate the
      starting reactants. 

PMID- 25046023
TI  - Soil sampling and isolation of entomopathogenic nematodes (Steinernematidae,
      Heterorhabditidae).
AB  - Entomopathogenic nematodes (a.k.a. EPN) represent a group of soil-inhabiting
      nematodes that parasitize a wide range of insects. These nematodes belong to two
      families: Steinernematidae and Heterorhabditidae. Until now, more than 70 species
      have been described in the Steinernematidae and there are about 20 species in the
      Heterorhabditidae. The nematodes have a mutualistic partnership with
      Enterobacteriaceae bacteria and together they act as a potent insecticidal
      complex that kills a wide range of insect species. Herein, we focus on the most
      common techniques considered for collecting EPN from soil. The second part of
      this presentation focuses on the insect-baiting technique, a widely used approach
      for the isolation of EPN from soil samples, and the modified White trap technique
      which is used for the recovery of these nematodes from infected insects. These
      methods and techniques are key steps for the successful establishment of EPN
      cultures in the laboratory and also form the basis for other bioassays that
      consider these nematodes as model organisms for research in other biological
      disciplines. The techniques shown in this presentation correspond to those
      performed and/or designed by members of S. P. Stock laboratory as well as those
      described by various authors. 

PMID- 25046024
TI  - Production of haploid zebrafish embryos by in vitro fertilization.
AB  - The zebrafish has become a mainstream vertebrate model that is relevant for many
      disciplines of scientific study. Zebrafish are especially well suited for forward
      genetic analysis of developmental processes due to their external fertilization,
      embryonic size, rapid ontogeny, and optical clarity--a constellation of traits
      that enable the direct observation of events ranging from gastrulation to
      organogenesis with a basic stereomicroscope. Further, zebrafish embryos can
      survive for several days in the haploid state. The production of haploid embryos
      in vitro is a powerful tool for mutational analysis, as it enables the
      identification of recessive mutant alleles present in first generation (F1)
      female carriers following mutagenesis in the parental (P) generation. This
      approach eliminates the necessity to raise multiple generations (F2, F3, etc.)
      which involves breeding of mutant families, thus saving the researcher time along
      with reducing the needs for zebrafish colony space, labor, and the husbandry
      costs. Although zebrafish have been used to conduct forward screens for the past
      several decades, there has been a steady expansion of transgenic and genome
      editing tools. These tools now offer a plethora of ways to create nuanced assays
      for next generation screens that can be used to further dissect the gene
      regulatory networks that drive vertebrate ontogeny. Here, we describe how to
      prepare haploid zebrafish embryos. This protocol can be implemented for novel
      future haploid screens, such as in enhancer and suppressor screens, to address
      the mechanisms of development for a broad number of processes and tissues that
      form during early embryonic stages.

PMID- 25046025
TI  - Photoresponsive phase separation of a poly(NIPAAm-co-SPO-co-fluorophore) random
      copolymer in W/O droplet.
AB  - The photoresponsive phase separation of a poly(N-isopropylacrylamide-co
      spironaphthoxazine methacryloyl-co-allyl-2-(2,6-bis((E)-4-(diphenylamino)styryl)
      4H-pyran-4-ylidene)-2-cyanoacetate) random copolymer, i.e., poly(NIPAAm-co-SPO-co
      fluorophore), in water-in-oil (W/O) droplets is described. The photoresponsive
      aqueous droplets were generated in the coflow regime of a simple tubular
      microfluidic device. The phase separation of the copolymer in the W/O droplets
      was induced by UV light at 365 nm and was affected significantly by the presence
      of 2,2-diethoxyacetophenone (DEAP) and sorbitan monooleate (Span 80). When the
      droplets were subjected to UV irradiation for more than 2 min, the phase
      separated copolymer was transferred completely from the aqueous droplet to the
      continuous phase of hexadecane. The phase separation arises from the
      photoisomerization shifting the spiro to the merocyanine form of the SPO pendant
      group in the copolymer, which in turn reduces the hydrophilicity of the copolymer
      via attractive hydrogen-bonding interactions between the merocyanine group and
      hydrophobic additives, i.e., Span 80, DEAP, and some stable fragments derived
      from the photocleavage of DEAP under UV irradiation. These interactions cause the
      copolymer to associate with the additives and then accelerate the phase
      separation of the copolymer and subsequent phase transfer of copolymer
      aggregates. The separate effects of DEAP and Span 80 were also investigated by UV
      spectrophotometric analysis of the rate coefficient of the reverse transformation
      (merocyanine to spiro) of the photochromic monomer. We propose a mechanism of
      phase separation of the copolymer in the W/O droplet based on the NMR and GC-MASS
      analyses of DEAP. 

PMID- 25046026
TI  - Development of a novel mouse model of amodiaquine-induced liver injury with a
      delayed onset.
AB  - Amodiaquine (AQ) treatment is associated with a high incidence of idiosyncratic
      drug-induced liver injury (IDILI) and agranulocytosis. Evidence suggests that AQ
      induced IDILI is immune mediated. A significant impediment to mechanistic studies
      of IDILI is the lack of valid animal models. This study reports the first animal
      model of IDILI with characteristics similar to mild IDILI in humans. Treatment of
      female C57BL/6 mice with AQ led to liver injury with delayed onset, which
      resolved despite continued treatment. Covalent binding of AQ was detected in the
      liver, which was greater in female than in male mice, and higher in the liver
      than in other organs. Covalent binding in the liver was maximal by Day 3, which
      did not explain the delayed onset of alanine aminotransferase (ALT) elevation.
      However, coincident with the elevated serum ALT, infiltration of liver and
      splenic mononuclear cells and activation of CD8 T-cells within the liver were
      identified. By Week 7, when ALT levels had returned close to normal, down
      regulation of several inflammatory cytokines and up-regulation of PD-1 on T-cells
      suggested induction of immune tolerance. Treatment of Rag1(-/-) mice with AQ
      resulted in higher ALT activities than C57BL/6 mice, which suggested that the
      adaptive immune response was responsible for immune tolerance. In contrast,
      depletion of NK cells significantly attenuated the increase in ALT, which implied
      a role for NK cells in mild AQ-induced IDILI. This is the first example of a
      delayed-onset animal model of IDILI that appears to be immune-mediated.

PMID- 25046027
TI  - Intravenous anesthetic propofol suppresses prostaglandin E2 and cysteinyl
      leukotriene production and reduces edema formation in arachidonic acid-induced
      ear inflammation.
AB  - Propofol is an intravenous drug widely used for anesthesia and sedation.
      Previously, propofol was shown to inhibit cyclo-oxygenase (COX) and 5
      lipoxygenase (5-LOX) activities. Because these enzyme-inhibiting effects have
      only been demonstrated in vitro, this study sought to ascertain whether similar
      effects might also be observed in vivo. In the current studies, effects of
      propofol were tested in a murine model of arachidonic acid-induced ear
      inflammation. Specifically, propofol - as a pre-treatment -- was
      intraperitoneally and then topical application of arachidonic acid was performed.
      After 1 h, tissue biopsies were collected and tested for the presence of edema
      and for levels of inflammatory mediators. The results indicated that the
      administration of propofol significantly suppressed ear edema formation, tissue
      myeloperoxidase activity, and tissue production of both prostaglandin E2 and
      cysteinyl leukotrienes. From the data, it can be concluded that propofol could
      exert anti-COX and anti-5-LOX activities in an in vivo model and that these
      activities in turn could have, at least in part, suppressed arachidonic acid
      induced edema formation in the ear.

PMID- 25046028
TI  - Intrastriatal injection of autologous blood or clostridial collagenase as murine
      models of intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a common form of cerebrovascular disease and is
      associated with significant morbidity and mortality. Lack of effective treatment
      and failure of large clinical trials aimed at hemostasis and clot removal
      demonstrate the need for further mechanism-driven investigation of ICH. This
      research may be performed through the framework provided by preclinical models.
      Two murine models in popular use include intrastriatal (basal ganglia) injection
      of either autologous whole blood or clostridial collagenase. Since, each model
      represents distinctly different pathophysiological features related to ICH, use
      of a particular model may be selected based on what aspect of the disease is to
      be studied. For example, autologous blood injection most accurately represents
      the brain's response to the presence of intraparenchymal blood, and may most
      closely replicate lobar hemorrhage. Clostridial collagenase injection most
      accurately represents the small vessel rupture and hematoma evolution
      characteristic of deep hemorrhages. Thus, each model results in different
      hematoma formation, neuroinflammatory response, cerebral edema development, and
      neurobehavioral outcomes. Robustness of a purported therapeutic intervention can
      be best assessed using both models. In this protocol, induction of ICH using both
      models, immediate post-operative demonstration of injury, and early post
      operative care techniques are demonstrated. Both models result in reproducible
      injuries, hematoma volumes, and neurobehavioral deficits. Because of the
      heterogeneity of human ICH, multiple preclinical models are needed to thoroughly
      explore pathophysiologic mechanisms and test potential therapeutic strategies. 

PMID- 25046029
TI  - Use of genetic technologies to compare medicines.
AB  - In order to ensure that patients receive the safest and most effective medicines
      possible, it is often necessary to compare medicines and assess the extent to
      which they are similar in their clinical impact. Full clinical trials with
      appropriate endpoints remain the only method to compare the clinical impact of
      two medicines with absolute certainty. Other available methods (including
      physicochemical analysis, genomics, and transcriptomics) can provide partial
      information about certain aspects of a medicine's biological impact, with
      possible clinical implications. Especially for biologics and non-biological
      complex drugs, which are more difficult to characterize by physicochemical means
      than small molecules, genomics and transciptomic studies can yield valuable
      insights for physicians, regulators, and drug developers. In this review, we cite
      and summarize a variety of studies that exemplify the emerging science of
      applying genomics and transcriptomics technologies to compare medicines. We
      discuss key aspects of experimental design, conduct of genetic assays, and
      advanced data analysis, all of which are critical for the successful execution of
      such studies. Finally, we propose new areas for which such studies can be applied
      to maximize patient benefit and reduce safety issues. 

PMID- 25046030
TI  - Application of a semi-homodesmotic approach in estimating ring strain energies
      (RSEs) of highly substituted cyclobutanes: RSEs for c-C4R8 that make sense.
AB  - A semi-homodesmotic method for estimating of ring strain energies (RSEs) of
      substituted cyclopropanes is applied to substituted cyclobutanes c-C4HxR8-x (R =
      F, Cl, Me; x = 0, 2, 4). Whereas (hyper)homodesmotic reaction methods predict
      implausible results, particularly for c-C4R8, the semi-homodesmotic approach
      provides RSEs consistent with thermodynamic and independent computational data
      regardless of the degree of substitution. The method requires employing
      homodesmotic group equivalent reactions only for disubstituted cyclobutanes,
      relying solely on absolute energy calculations for more substituted rings. We
      find that, consistent with QTAIM data, RSEs increase with substitution regardless
      of the electronic nature of R, although the increase is more dramatic when R is
      electron-withdrawing. Overall, the semi-homodesmotic method is simpler than
      hyperhomodesmotic approaches and gives more trustworthy results. 

PMID- 25046031
TI  - Lacosamide-induced atrial tachycardia in a child with hypoplastic left-heart
      syndrome: the importance of assessing additional proarrhythmic risks.
AB  - Antiepileptic medications have been reported to cause disturbances in cardiac
      conduction. Lacosamide decreases seizure burden by modulating sodium channels.
      Although it has been demonstrated to have few side effects, there have been
      reports of clinically significant cardiac conduction disturbances. We report the
      case of a child with hypoplastic left-heart syndrome and well-controlled
      multifocal atrial tachycardia who developed haemodynamically significant atrial
      tachycardia after receiving two doses of lacosamide. 

PMID- 25046032
TI  - Transrectal ultrasonography (TRUS)-guided pelvic plexus block to reduce pain
      during prostate biopsy: a randomised controlled trial.
AB  - OBJECTIVE: To assess the role of pelvic plexus block (PPB) in reducing pain
      during transrectal ultrasonography(TRUS)-guided prostate biopsy, compared with
      the conventional periprostatic nerve block (PNB). PATIENTS AND METHODS: A
      prospective, double-blind observational study was conducted with patients being
      randomised into three groups. Group-1 (47 patients) received intrarectal local
      anaesthesia (IRLA) with 10 mL 2% lignocaine jelly along with pelvic plexus block
      (PPB) with 2.5 mL 2% lignocaine injection bilaterally. Group-2 (46 patients)
      received IRLA with periprostatic nerve block (PNB). Group-3 (46 patients)
      received only IRLA without any type of nerve block. The patients were requested
      to rate the level of pain from 0 to 10 on a visual analogue scale (VAS) at two
      time points: VAS-1: during biopsy procedure and VAS-2: 30 min after the
      procedure. RESULTS: The mean age of the patients, mean volume of the prostates
      and mean serum PSA values were comparable among the three groups. The mean pain
      score during biopsy was significantly less in the PPB group [mean (range) sore of
      2.91 (2-4)] compared with the PNB group [mean (range) score of 4 (3-5)], and both
      these groups were superior to the no nerve block group [mean score of 5.4 (3-7)].
      There was no significant difference between the mean pain scores, 30 min after
      the procedure among the three groups with the mean (range) scores being 2.75 (2
      4), 2.83 (2-4) and 2.85 (2-4), respectively. CONCLUSION: PPB is superior to
      conventional periprostatic nerve block (PNB) for pain control during TRUS-guided
      biopsy and both are in turn superior to no nerve block.

PMID- 25046033
TI  - Nanoliter qPCR platform for highly parallel, quantitative assessment of reductive
      dehalogenase genes and populations of dehalogenating microorganisms in complex
      environments.
AB  - Idiosyncratic combinations of reductive dehalogenase (rdh) genes are a
      distinguishing genomic feature of closely related organohalogen-respiring
      bacteria. This feature can be used to deconvolute the population structure of
      organohalogen-respiring bacteria in complex environments and to identify relevant
      subpopulations, which is important for tracking interspecies dynamics needed for
      successful site remediation. Here we report the development of a nanoliter qPCR
      platform to identify organohalogen-respiring bacteria and populations by
      quantifying major orthologous reductive dehalogenase gene groups. The qPCR assays
      can be operated in parallel within a 5184-well nanoliter qPCR (nL-qPCR) chip at a
      single annealing temperature and buffer condition. We developed a robust
      bioinformatics approach to select from thousands of computationally proposed
      primer pairs those that are specific to individual rdh gene groups and compatible
      with a single amplification condition. We validated hundreds of the most
      selective qPCR assays and examined their performance in a trichloroethene
      degrading bioreactor, revealing population structures as well as their unexpected
      shifts in abundance and community dynamics. 

PMID- 25046034
TI  - Bioactive nanoparticle-gelatin composite scaffold with mechanical performance
      comparable to cancellous bones.
AB  - Mechanical properties are among the most concerned issues for artificial bone
      grafting materials. The scaffolds used for bone grafts are either too brittle
      (glass) or too weak (polymer), and therefore composite scaffolds are naturally
      expected as the solution. However, despite the intensive studies on composite
      bone grafting materials, there still lacks a material that could be matched to
      the natural cancellous bones. In this study, nanosized bioactive particles (BP)
      with controllable size and good colloidal stability were used to composite with
      gelatin, forming macroporous scaffolds. It was found that the mechanical
      properties of obtained composite scaffolds, in terms of elastic modulus,
      compressive strength, and strain at failure, could match to that of natural
      cancellous bones. This is ascribed to the good distribution of particle in matrix
      and strong interaction between particle and gelatin. Furthermore, the
      incorporation of BPs endues the composite scaffolds with bioactivity, forming HA
      upon reacting with simulated body fluid (SBF) within days, thus stimulating
      preosteoblasts attachment, growth, and proliferation in these scaffolds. Together
      with their good mechanical properties, these composite scaffolds are promising
      artificial bone grating materials. 

PMID- 25046035
TI  - Synthesis and electrocatalytic water oxidation by electrode-bound helical peptide
      chromophore-catalyst assemblies.
AB  - Artificial photosynthesis based on dye-sensitized photoelectrosynthesis cells
      requires the assembly of a chromophore and catalyst in close proximity on the
      surface of a transparent, high band gap oxide semiconductor for integrated light
      absorption and catalysis. While there are a number of approaches to assemble
      mixtures of chromophores and catalysts on a surface for use in artificial
      photosynthesis based on dye-sensitized photoelectrosynthesis cells, the synthesis
      of discrete surface-bound chromophore-catalyst conjugates is a challenging task
      with few examples to date. Herein, a versatile synthetic approach and
      electrochemical characterization of a series of oligoproline-based light
      harvesting chromophore-water-oxidation catalyst assemblies is described. This
      approach combines solid-phase peptide synthesis for systematic variation of the
      backbone, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) as an orthogonal
      approach to install the chromophore, and assembly of the water-oxidation catalyst
      in the final step. Importantly, the catalyst was found to be incompatible with
      the conditions both for amide bond formation and for the CuAAC reaction. The
      modular nature of the synthesis with late-stage assembly of the catalyst allows
      for systematic variation in the spatial arrangement of light-harvesting
      chromophore and water-oxidation catalyst and the role of intrastrand distance on
      chromophore-catalyst assembly properties. Controlled potential electrolysis
      experiments verified that the surface-bound assemblies function as water
      oxidation electrocatalysts, and electrochemical kinetics data demonstrate that
      the assemblies exhibit greater than 10-fold rate enhancements compared to the
      homogeneous catalyst alone. 

PMID- 25046036
TI  - Cation-size-controlled assembly of the Ni(Ac)2-1,4-H2NDC system: geminal
      dicationic ionothermal syntheses, crystal structures and magnetic properties.
AB  - Geminal dicationic ionic liquids with different alkyl spacer lengths regularly
      tune four MOF structures of two structure types in the Ni(Ac)2-1,4-H2NDC system,
      which in turn bring about the magnetic properties divided into antiferromagnetic
      and ferromagnetic couplings consistent with the structures. 

PMID- 25046037
TI  - Frictional dynamics of stiff monolayers: from nucleation dynamics to thermal
      sliding.
AB  - The inherently nonlinear dynamics of two surfaces as they are driven past each
      other, a phenomenon known as dry friction, has yet to be fully understood on an
      atomistic level. New experiments on colloidal monolayers forced over laser
      generated substrates now offer the opportunity to investigate friction with
      single-particle resolution. Here, we use analytical theory and computer
      simulations to study the effect of thermal fluctuations on the stick-slip
      mechanism characteristic for the frictional response of a stiff colloidal
      monolayer on a commensurate substrate. By performing a harmonic expansion of the
      energy and employing elementary statistical mechanics, we map the motion of the
      monolayer onto a simple differential equation. Analytical expressions derived
      from our approach predict a transition from nucleation dynamics, where the
      monolayer moves in a sequence of activated hops over energy barriers, to "thermal
      sliding", in which the effective substrate barrier opposing the motion of the
      monolayer disappears due to thermal fluctuations, leading to continuous,
      uninterrupted sliding motion. Furthermore, we find that the average velocity of
      the monolayer for large driving forces obeys a simple scaling behavior that is
      consistent with the existence of a static friction. For small forces, however,
      nucleation provides a mode of motion that leads to a small but non-vanishing
      mobility of the monolayer. Data obtained from simulations confirm this picture
      and agree quantitatively with our analytical formulae. The theory developed here
      holds under general conditions for sufficiently strong inter-particle repulsions
      and it yields specific predictions that can be tested in experiments. 

PMID- 25046038
TI  - The nanocrystal superlattice pressure cell: a novel approach to study molecular
      bundles under uniaxial compression.
AB  - Ordered assemblies of inorganic nanocrystals coated with organic linkers present
      interesting scientific challenges in hard and soft matter physics. We demonstrate
      that a nanocrystal superlattice under compression serves as a nanoscopic pressure
      cell to enable studies of molecular linkers under uniaxial compression. We
      developed a method to uniaxially compress the bifunctional organic linker by
      attaching both ends of aliphatic chains to neighboring PbS nanocrystals in a
      superlattice. Pressurizing the nanocrystal superlattice in a diamond anvil cell
      thus results in compression of the molecular linkers along their chain direction.
      Small-angle and wide-angle X-ray scattering during the compression provide
      insights into the structure of the superlattice and nanocrystal cores under
      compression, respectively. We compare density functional theory calculations of
      the molecular linkers as basic Hookean springs to the experimental force-distance
      relationship. We determine the density of linkers on the nanocrystal surfaces. We
      demonstrate our method to probe the elastic force of single molecule as a
      function of chain length. The methodology introduced in this paper opens doors to
      investigate molecular interactions within organic molecules compressed within a
      nanocrystal superlattice. 

PMID- 25046039
TI  - Organic-inorganic mixed-valence systems with strongly-coupled triarylamine and
      cyclometalated osmium.
AB  - Organic-inorganic mixed-valence systems with strongly-coupled triarylamine and
      cyclometalated osmium have been developed. They display two well-separated redox
      couples at low potentials. Each of the three readily accessible oxidation states
      can be distinguished by the absorbance at three different wavelengths. 

PMID- 25046040
TI  - Interpersonal functioning in obsessive-compulsive personality disorder.
AB  - The core symptoms of obsessive-compulsive personality disorder (OCPD) often lead
      to interpersonal difficulties. However, little research has explored
      interpersonal functioning in OCPD. This study examined interpersonal problems,
      interpersonal sensitivities, empathy, and systemizing, the drive to analyze and
      derive underlying rules for systems, in a sample of 25 OCPD individuals, 25
      individuals with comorbid OCPD and obsessive-compulsive disorder (OCD), and 25
      healthy controls. We found that OCPD individuals reported hostile-dominant
      interpersonal problems and sensitivities with warm-dominant behavior by others,
      whereas OCPD+OCD individuals reported submissive interpersonal problems and
      sensitivities with warm-submissive behavior by others. Individuals with OCPD,
      with and without OCD, reported less empathic perspective taking relative to
      healthy controls. Finally, we found that OCPD males reported a higher drive to
      analyze and derive rules for systems than OCPD females. Overall, results suggest
      that there are interpersonal deficits associated with OCPD and the clinical
      implications of these deficits are discussed. 

PMID- 25046041
TI  - Regulated bioanalysis in Brazil: is the country ready to move on?

PMID- 25046042
TI  - Understanding the matrix effect in immunoassays.

PMID- 25046044
TI  - Method transfer in the bioanalytical laboratory.

PMID- 25046045
TI  - Reasons for calibration standard curve slope variation in LC-MS assays and how to
      address it.

PMID- 25046046
TI  - Measuring NAD(+) levels in mouse blood and tissue samples via a surrogate matrix
      approach using LC-MS/MS.
AB  - BACKGROUND: NAD(+) is an endogenous analyte and is unstable during blood sample
      collection, both of which present obstacles for quantitation. Moreover, current
      procedures for NAD(+) sample collection require onsite treatment with strong acid
      to stabilize the NAD(+) in mouse blood cells. RESULTS: NAD(+) can be stabilized
      by addition of acid before the frozen mouse blood sample was thawed. A simple
      sample collection procedure was proposed to facilitate the analysis of NAD(+) in
      mouse blood and tissue samples. A LC-MS/MS method was developed for quantifying
      NAD(+) in mouse blood and various tissue samples. The described method was used
      to measure endogenous NAD(+) levels in mouse blood following oral administration
      of the nicotinamide phosphoribosyltransferase inhibitor GNE-617. CONCLUSION: This
      study presents a suitable assay and sample collection procedure for high
      throughput screening of NAD(+) samples in preclinical discovery studies.

PMID- 25046047
TI  - Assessment of cardiovascular disease risk using immunosensors for determination
      of C-reactive protein levels in serum and saliva: a pilot study.
AB  - BACKGROUND: Disposable immunosensors based on field effect transistors with
      single-walled carbon nanotubes (NTFET) were applied for the first time to
      clinical samples of undiluted blood serum and saliva for the determination of C
      reactive protein (CRP), and validated by comparison with ELISA. RESULTS: The
      NTFET showed comparable analytical performance with the ELISA when applied to
      clinical samples, which means that NTFET can be used as an alternative to ELISA.
      Also, a high correlation between the serum and salivary CRP levels was found with
      the NTFET, which means that saliva could be used based on a noninvasive sampling
      as an alternative fluid to blood serum. The establishment of a new range of CRP
      levels based on saliva was also found. CONCLUSION: The monitoring of CRP in
      saliva samples by disposable immunosensors could be a valuable approach for the
      improvement of healthcare services, considering the worldwide increased incidence
      of cardiovascular diseases.

PMID- 25046049
TI  - Dried blood spot testing: a novel approach for the therapeutic drug monitoring of
      ziprasidone-treated patients.
AB  - BACKGROUND: A novel analytical approach, based on dried blood spot (DBS) testing,
      has been developed, validated and applied for the first time to the analysis of
      ziprasidone (ZPR) for the therapeutic drug monitoring (TDM) of schizophrenic
      patients. DBS represent a more feasible but reliable matrix, alternative to blood
      and plasma. METHODS: The assays were carried out using an HPLC method with native
      fluorescence. Blood drops were applied to DBS cards and dried by microwaves, an
      internal standard solution was added to the DBS and 5-mm punches were cut out for
      analysis. ZPR was extracted from DBS with methanol, giving good extraction
      yields, precision and selectivity results. RESULTS: The method was applied with
      satisfactory results to DBS samples from psychiatric patients to determine ZPR
      levels for therapy optimization. CONCLUSION: This innovative methodology provides
      reliable and significant TDM information, with important advantages over
      classical blood sampling in terms of collection, storage and processing.

PMID- 25046048
TI  - Metabolite profiling of RCS-4, a novel synthetic cannabinoid designer drug, using
      human hepatocyte metabolism and TOF-MS.
AB  - BACKGROUND: Since 2009, scheduling legislation of synthetic cannabinoids prompted
      new compound emergence to circumvent legal restrictions. 2-(4-methoxyphenyl)-1-(1
      pentyl-indol-3-yl)methanone (RCS-4) is a potent cannabinoid receptor agonist sold
      in herbal smoking blends. Absence of parent synthetic cannabinoids in urine
      suggests the importance of metabolite identification for detecting RCS-4
      consumption in clinical and forensic investigations. Materials & methods &
      Results: With 1 h human hepatocyte incubation and TOF high-resolution MS, we
      identified 18 RCS-4 metabolites, many not yet reported. Most metabolites were
      hydroxylated with or without demethylation, carboxylation and dealkylation
      followed by glucuronidation. One additional sulfated metabolite was also
      observed. O-demethylation was the most common biotransformation and generated the
      major metabolite. CONCLUSION: For the first time, we present a metabolic scheme
      of RCS-4 obtained from human hepatocytes, including Phase I and II metabolites.
      Metabolite structural information and associated high-resolution mass spectra can
      be employed for developing clinical and forensic laboratory RCS-4 urine screening
      methods.

PMID- 25046050
TI  - Development of miniature mass spectrometry systems for bioanalysis outside the
      conventional laboratories.
AB  - Mass spectrometry (MS) is known for highly specific and sensitive analysis. The
      general applicability of this technique makes it a good candidate for biological
      applications over a much broader range than is now the case. The limiting factors
      preventing MS from being applied at the biologist's bench or in a physician's
      office are identified as the large size of the systems, as well as the
      complicated analytical procedures required. An approach for developing miniature
      MS analysis systems with simplified operational procedures is described and the
      associated technical developments are discussed. 

PMID- 25046051
TI  - Strategic characterization of anti-drug antibody responses for the assessment of
      clinical relevance and impact.
AB  - All therapeutic proteins have the potential to induce anti-drug antibodies (ADA).
      Clinically relevant ADA can impact efficacy and/or safety of a biological
      therapeutic. Immunogenicity assessment strategy evaluates binding and
      neutralizing ADA, and the need for additional characterization (e.g., epitope,
      titer and so on) is determined using a risk-based approach. The choice of
      characterization assays depends on the type, application and immunogenicity of
      the therapeutic. ADA characterization can impact the interpretation of the risk
      profile of a given therapeutic, and offers insight into opportunities for risk
      mitigation and management. This article describes common ADA characterization
      methods. Strategic assessment and characterization of clinically relevant ADA are
      discussed, in order to support clinical options for safe and effective patient
      care and disease management. 

PMID- 25046052
TI  - LC-MS of oligonucleotides: applications in biomedical research.
AB  - Recent findings have elucidated numerous novel biological functions for
      oligonucleotides. Current standard methods for the study of oligonucleotides
      (i.e., hybridization and PCR) are not fully equipped to deal with the
      experimental needs arising from these new discoveries. More importantly, as the
      intracellular capacity of oligonucleotides is being harnessed for biomedical
      applications, alternative bioanalytical techniques become indispensable in order
      to comply with ever-increasing regulatory requirements. Owing to its ability to
      detect oligonucleotides independent of their sequence, LC-MS is emerging as the
      analytical method of choice for oligonucleotides. In this article, the current
      applications of LC-MS in the analysis of oligonucleotides, with an emphasis on
      RNA therapeutics and biomarkers, will be examined. In addition, the theoretical
      framework of oligonucleotide ESI is carefully inspected with the purpose of
      identifying the contributing factors to MS signal intensity. 

PMID- 25046053
TI  - Bioanalysis of urine samples after manipulation by oxidizing chemicals: technical
      considerations.
AB  - Drug testing programs are established to help achieve a drug-free work
      environment, promote fair competition in sport, facilitate harm minimization and
      rehabilitation programs, better manage patient care by clinicians and service law
      enforcement authorities. Urine remains the most popular and appropriate testing
      matrix for such purposes. However, urine is prone to adulteration, where
      chemicals, especially oxidizing chemicals, are purposely added to the collected
      urine specimens to produce a false-negative test result. This article will
      describe the effect of various popular oxidizing adulterants on urine drug test
      results, the countermeasures taken by laboratories in dealing with adulterated
      urine samples and the prospect of developing more robust and economical methods
      to combat urine adulteration in the future. 

PMID- 25046054
TI  - Applications of cell-based bioassays measuring the induced expression of
      endogenous genes.
AB  - Cell-based bioassays are used to determine the biological activity of complex
      biotherapeutic products, to assign potency and to assure the quality and
      consistency of the manufacturing process. Clinically, these assays are used to
      assess bioactivity in patient samples, particularly for the detection of antidrug
      neutralizing antibodies. Owing to their versatility, cellular assays that measure
      endogenous gene expression by quantitative reverse transcription PCR offer a
      rapid and automatable alternative to assays measuring functional, late-stage
      responses. Notably, detection of immediate early gene expression represents a
      direct response of the cell to receptor ligation by the biotherapeutic. We review
      current developments in the use of this approach and demonstrate its application
      to the detection of receptor-binding autoantibodies using, as a case study, the
      detection of autoantibodies to the thyroid-stimulating hormone receptor. 

PMID- 25046056
TI  - The balance effect of acupuncture therapy among stroke patients.
AB  - OBJECTIVE: To analyze how acupuncture therapy affects balance in patients
      experiencing their first stroke and to identify the stroke group with greatest
      improvement in balance after acupuncture intervention. DESIGN: Retrospective case
      control study. SETTING: Ward of a medical university hospital. PARTICIPANTS: A
      total of 629 stroke patients were enrolled initially; 345 patients met the study
      criteria and 132 were analyzed (66 each in the study and control groups).
      INTERVENTIONS: The study group received physiotherapy combined with acupuncture
      and the control group received only physiotherapy. MAIN OUTCOME MEASURES: The
      Postural Assessment Scale for Stroke patients (PASS) was used to evaluate
      balance. This balance scale system can be subdivided into static balance (PASS
      MP, maintain posture) and dynamic balance (PASS-CP, change posture). RESULTS:
      This study revealed no statistically significant improvement of balance in the
      study group (t test). When patients with high Brunnstrom stage (Br stage) and low
      Br stage were analyzed separately, once again no statistical difference was
      detected between the study and control groups of those with high Br stage.
      However, among low-Br stage patients, the study group showed significant
      improvement in static balance (mean PASS-MP score+/-standard deviation: 4.7+/
      3.7) compared with the control group (PASS-MP score: 2.8+/-2.7) (p<0.05).
      CONCLUSIONS: In first-ever stroke patients with a low Br stage, acupuncture
      therapy can improve static balance during rehabilitation. However, the effect on
      balance was limited among high-Br stage patients. This study provides information
      valuable to patients with hemiplegic stroke because it suggests that acupuncture
      can be used to improve balance. A prospective double-blind, randomized,
      controlled study design is recommended for future studies in patients with
      hemiplegic stroke.

PMID- 25046055
TI  - Glycemic/metabolic responses to identical meal tolerance tests at breakfast,
      lunch and dinner in Japanese patients with type 2 diabetes mellitus treated with
      a dipeptidyl peptidase-4 inhibitor and the effects of adding a
      mitiglinide/voglibose fixed-dose combination.
AB  - BACKGROUND: The effects of the mitiglinide/voglibose fixed-dose combination on
      postprandial glycemic/metabolic responses in patients with type 2 diabetes
      mellitus (T2DM) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors are
      unknown. METHODS: Twelve T2DM patients treated with a DPP-4 inhibitor underwent
      identical meal tolerance tests (MTTs) at breakfast, lunch and dinner, before and
      2 - 3 weeks after treatment with a fixed-dose combination of mitiglinide 10 mg
      and voglibose 0.2 mg (combination). Patients were randomized in a cross-over
      fashion to administer the combination either three-times-daily before each meal
      or twice-daily before breakfast and dinner. Glycemic/metabolic responses were
      evaluated at 0, 30, 60 and 120 min in each MTT. RESULTS: Three-times-daily
      administration of the combination significantly suppressed postprandial
      hyperglycemia after each meal, particularly after lunch and dinner. Active
      glucagon-like peptide-1 levels increased significantly after each meal, as did
      early-phase insulin secretion without excessive insulin secretion. Postprandial
      hyperglycemia after lunch was significantly greater after twice-daily than three
      times-daily administration, but there were no clinically relevant differences in
      other metabolic responses. CONCLUSION: This study revealed that adding the
      mitiglinide/voglibose combination to a DPP-4 inhibitor elicited additive
      improvements in postprandial glycemic/metabolic responses assessed using MTTs at
      breakfast, lunch and dinner with identical meal compositions.

PMID- 25046057
TI  - Development of amelogenin-chitosan hydrogel for in vitro enamel regrowth with a
      dense interface.
AB  - Biomimetic enamel reconstruction is a significant topic in material science and
      dentistry as a novel approach for the treatment of dental caries or erosion.
      Amelogenin has been proven to be a critical protein for controlling the organized
      growth of apatite crystals. In this paper, we present a detailed protocol for
      superficial enamel reconstruction by using a novel amelogenin-chitosan hydrogel.
      Compared to other conventional treatments, such as topical fluoride and
      mouthwash, this method not only has the potential to prevent the development of
      dental caries but also promotes significant and durable enamel restoration. The
      organized enamel-like microstructure regulated by amelogenin assemblies can
      significantly improve the mechanical properties of etched enamel, while the dense
      enamel-restoration interface formed by an in situ regrowth of apatite crystals
      can improve the effectiveness and durability of restorations. Furthermore,
      chitosan hydrogel is easy to use and can suppress bacterial infection, which is
      the major risk factor for the occurrence of dental caries. Therefore, this
      biocompatible and biodegradable amelogenin-chitosan hydrogel shows promise as a
      biomaterial for the prevention, restoration, and treatment of defective enamel. 

PMID- 25046058
TI  - African American women's perceptions and attitudes regarding participation in
      medical research: the Mayo Clinic/The Links, Incorporated partnership.
AB  - OBJECTIVE: To examine perceptions and attitudes toward health-related research
      participation among professional African American women. METHODS: Participants
      were members of an African American women's service organization, The Links,
      Incorporated. Data were collected via self-administered questionnaires at The
      Links, Incorporated 2012 National Assembly. Sociodemographics, prior research
      experience, intention to participate (ITP), willingness to participate (WTP) in a
      variety of research studies and attitudes about research participation were
      measured. RESULTS: A total of 381 surveys were analyzed. A majority of
      respondents were married (66%), employed (69%), and college educated (96%).
      Median age was 59; 38% reported prior research participation. Overall, 78% agreed
      with the statement, "Participation in research will mean better care," 24% agreed
      "Participation in research is risky" and 3% agreed "Scientists cannot be
      trusted." Fifty-two percent agreed with the statement, "Research conducted in the
      U.S. is ethical." Mean ITP in research was 4.9+/-1.7 on a rating scale of 1
      ("definitely no") to 7 ("definitely yes"). WTP was highest for an interview study
      and providing a blood sample, and lowest for clinical trial and medical record
      review. CONCLUSION: Attitudes toward research participation were generally
      favorable among professional African American women; many expressed WTP in a
      variety of research study types.

PMID- 25046059
TI  - Timing of emergency department visits for childhood asthma after initial inhaled
      corticosteroid use.
AB  - Inhaled corticosteroids can prevent acute exacerbations and emergency visits when
      used as part of a chronic care plan for long-term control of asthma, but low
      patient adherence and inadequate provider prescribing (clinical inertia) can
      limit these benefits. State Medicaid programs are a major source of insurance
      coverage for low-income children, paying for medications and preventive care, as
      well as bearing the cost of adverse outcomes for common chronic conditions in
      childhood, such as asthma. This study measured the incidence and timing of
      emergency department (ED) visits in the first 90 days after an initial inhaled
      corticosteroid prescription (ICS-Rx) among 43,156 Medicaid-enrolled children with
      a diagnosis of asthma in 14 southern states in 2007. One in 5 children (19.6%)
      with asthma had at least 1 ED visit in the first 90 days after initial ICS-Rx;
      10% of these visits occurred within the first 48 hours, and 25% occurred within
      the first week. Continued ICS-Rx use was associated with lower risk of an ED
      visit. There were no racial differences in the ED visit rates. Initial ICS-Rx for
      Medicaid-enrolled children is a warning flag for short-term risk of asthma
      related ED visits, whereas continued ICS-Rx use is protective for at least 90
      days. Primary care follow-up may be needed within the first 2 days after initial
      ICS-Rx to prevent adverse outcomes. Medicaid programs could use claims data for
      surveillance of adherence to guideline-concordant therapy and for sentinel events
      marking windows of a higher risk for ED visits. Population Health Management
      2015;18:54-60. 

PMID- 25046060
TI  - Hesperidin restores experimentally induced neurotoxicity in Wistar rats.
AB  - Carbon tetrachloride (CCl4) is a highly toxic industrial solvent with pronounced
      systemic toxicity including brain. Neurotoxicity may be a direct result of
      hepatic dysfunction from CCl4 intoxication. Over the years CCl4 has been used as
      an excellent model for studying experimentally induced neurotoxicity in murine
      models. Hesperidin (HP) is a known cytoprotectant with comprehensive anti-oxidant
      and neuroprotective properties. The aim of the present study was to evaluate
      experimentally induced neurotoxicity by CCl4 and its abrogation by using
      antioxidant potential of HP. CCl4 caused a significant enhancement in the lipid
      peroxidation (LPO) levels and protein carbonyl (PC) content. HP supplementation
      significantly restored the LPO levels and PC content. It also replenished the
      altered enzymatic and non-enzymatic antioxidants in brain tissues of rats. The
      neurotoxicity markers were also restored to normalcy with HP treatment. It is
      suggested that HP, by attenuating neuronal oxidative stress, holds promise that
      can ameliorate CCl4-induced neurotoxicity. HP has the potential to be explored as
      a universal neuroprotectant in xenobiotically induced neurotoxicity mediated by
      oxidative stress.

PMID- 25046061
TI  - Efficacy of an evidence-based ARV adherence intervention in China.
AB  - We designed a randomized controlled trial of a home based intervention to improve
      antiretroviral adherence and to assess the impact of depressive symptoms among
      people living with HIV in Hunan, China. At baseline, 110 subjects reported taking
      90% or less of prescribed medication. At 6 months, when the intervention ended,
      56% of subjects in the control and 87% of subjects in the experimental group were
      adherent. This difference was maintained at 12 months. In multivariate analyses,
      controlling for baseline visual analogue adherence scale, stigma, social support,
      and Center for Epidemiological Studies Depression scale, the experimental group
      had a significantly higher proportion of people who were adherent (p=0.009). The
      high prevalence of significant depressive symptoms (67%) at baseline is of
      concern. It is of particular importance that future studies look at the types of
      depression likely to be seen in these patients and differentiate early between
      those likely to benefit from HIV-related support and those who will require
      additional depression-targeted interventions.

PMID- 25046062
TI  - Latest approaches for efficient protein production in drug discovery.
AB  - INTRODUCTION: Pharmaceutical research looks to discover and develop new compounds
      which influence the function of disease-associated proteins or respective protein
      protein interactions. Various scientific methods are available to discover those
      compounds, such as high-throughput screening of a library comprising chemical or
      natural compounds and computational rational drug design. The goal of these
      methods is to identify the seed compounds of future pharmaceuticals through the
      use of these technologies and laborious experiments. For every drug discovery
      effort made, the possession of accurate functional and structural information of
      the disease-associated proteins helps to assist drug development. Therefore, the
      investigation of the tertiary structure of disease-associated proteins and
      respective protein-protein interactions at the atomic level are of crucial
      importance for successful drug discovery. AREAS COVERED: In this review article,
      the authors broadly outline current techniques utilized for recombinant protein
      production. In particular, the authors focus on bacterial expression systems
      using Escherichia coli as the living bioreactor. EXPERT OPINION: The recently
      developed pCold-glutathione S-transferase (GST) system is one of the best systems
      for soluble protein expression in E. coli. Where the pCold-GST system does not
      succeed, it is preferable to change the host from E. coli to higher organisms
      such as yeast expression systems like Pichia pastoris and Kluyveromyces lactis.
      The selection of an appropriate expression system for each desired protein and
      the optimization of experimental conditions significantly contribute toward the
      successful outcome of any drug discovery study.

PMID- 25046063
TI  - Inchworming: a novel motor stereotypy in the BTBR T+ Itpr3tf/J mouse model of
      autism.
AB  - Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental
      disorder characterized by decreased reciprocal social interaction, abnormal
      communication, and repetitive behaviors with restricted interest. As diagnosis is
      based on clinical criteria, any potentially relevant rodent models of this
      heterogeneous disorder should ideally recapitulate these diverse behavioral
      traits. The BTBR T+ Itpr3tf/J (BTBR) mouse is an established animal model of ASD,
      displaying repetitive behaviors such as increased grooming, as well as cognitive
      inflexibility. With respect to social interaction and interest, the juvenile play
      test has been employed in multiple rodent models of ASD. Here, we show that when
      BTBR mice are tested in a juvenile social interaction enclosure containing
      sawdust bedding, they display a repetitive synchronous digging motion. This
      repetitive motor behavior, referred to as "inchworming," was named because of the
      stereotypic nature of the movements exhibited by the mice while moving
      horizontally across the floor. Inchworming mice must use their fore- and hind
      limbs in synchrony to displace the bedding, performing a minimum of one inward
      and one outward motion. Although both BTBR and C56BL/6J (B6) mice exhibit this
      behavior, BTBR mice demonstrate a significantly higher duration and frequency of
      inchworming and a decreased latency to initiate inchworming when placed in a
      bedded enclosure. We conclude that this newly described behavior provides a
      measure of a repetitive motor stereotypy that can be easily measured in animal
      models of ASD.

PMID- 25046064
TI  - [Effect of radiofrequency thermal ablation treatment on nasal mucociliary
      clearance in patients with isolated inferior turbinate hypertrophy].
AB  - OBJECTIVES: This study aims to evaluate the effect of the radiofrequency thermal
      ablation on nasal mucociliary clearance in patients with isolated inferior concha
      hypertrophy. PATIENTS AND METHODS: Thirty patients (10 females, 20 males; mean
      age 31.0+/-12.0 years; range 18 to 61 years) who were admitted to our clinic with
      a complaint of chronic nasal obstruction and diagnosed with isolated inferior
      concha submucosal hypertrophy between May 2009 and December 2009 were included.
      Radiofrequency thermal ablation was applied to the inferior concha at three
      separate points with 350 joule at 75  degrees C as a treatment. Nasal mucociliary
      clearance was evaluated through saccharin clearance test in pre- and
      postoperative (at eight weeks) period. RESULTS: The mean pre- and postoperative
      saccharin clearance tests were 565.4+/-253.9 sec and 558.7+/-257.7 sec,
      respectively. However, there was no significant difference in two measurements
      (p>0.05). CONCLUSION: Our study results show that radiofrequency thermal ablation
      application for the treatment of isolated inferior concha hypertrophy has no
      effect on nasal mucociliary clearance.

PMID- 25046065
TI  - [Comparison of rhinomanometry results with polysomnography and physical
      examination findings in patients with obstructive sleep apnea syndrome].
AB  - OBJECTIVES: This study aims to investigate the effects of anterior rhinomanometry
      induced nasal resistance on obstructive sleep apnea syndrome (OSAS) patients.
      PATIENTS AND METHODS: Between May 2011 and September 2011, 100 volunteer patients
      (76 males, 24 females; mean age 47.6+/-11.6 years; range 20 to 71 years) who were
      admitted with complaints of snore, breathing pauses told by their partners,
      oversleep mood in a daytime and fatigue and diagnosed with OSAS by
      polysomnography with simple snore were included. Anterior rhinomanometry was
      applied for all patients and nasal resistance was estimated. Mallampati index and
      body mass index (BMI) of patients was calculated. The mean apnea-hypopnea index
      (AHI) and minimum oxygen saturation values were measured. RESULTS: There was no
      significant relationship between nasal resistance and AHI. However, a significant
      relationship between AHI and Mallampati and BMI values was observed. The AHI
      values increased, as the Mallampati and BMI values increased. CONCLUSION: Our
      study results show that nasal resistance has no significant effect on AHI and
      minimum oxygen saturation in OSAS patients.

PMID- 25046066
TI  - [Mold hypersensitivity in children with frequent respiratory tract infection and
      prolonged cough attacks].
AB  - OBJECTIVES: This study aims to investigate pollen, mite and mold sensitivities
      among children with frequent respiratory tract infection living in damp
      apartments and to evaluate the effects of separated parents, education status,
      ethnicity, the presence of siblings, and their atopy status on the development of
      atopy. PATIENTS AND METHODS: Between June 2012 and September 2013, 63 children
      (28 girls, 35 boys; mean age 80.2 years; range 24 to 97 years) who were admitted
      to Acibadem Bodrum Hospital with at least six respiratory tract infection per
      year with mold exposure and prolonged cough attacks and underwent skin prick test
      (SPT) were included. Skin prick test-positive patients were further divided into
      groups according to the upper respiratory tract (URT) or lower respiratory tract
      (LRT) involvement and were assessed for mold, mite and pollen sensitivities.
      RESULTS: One-third of the patients were SPT positive. The parents of these
      patients had physician-diagnosed allergy (p<0.05). Most patients with mite
      sensitivity presented with URT and LRT findings (p<0.05). Pollen-sensitive
      patients had predominantly URT findings (p<0.05). All children with mold
      sensitivity presented with LRT findings (p<0.05). CONCLUSION: Atopic children may
      experience more frequent LRT symptoms when exposed to molds than non-atopic
      children. Mold exposure may also cause inflammation at LRT without causing
      immunoglobulin E-dependent sensitization.

PMID- 25046067
TI  - [The effect of allergy on prognosis of surgically treated nasal polyposis].
AB  - OBJECTIVES: This study aims to investigate the effects of allergy existence on
      prognosis of surgically treated nasal polyposis. PATIENTS AND METHODS: This
      prospective study included 29 patients (22 males, 7 females; mean age 45.9 years;
      range 21 to 72 years) admitted to our clinic with nasal polyposis between January
      2006 and December 2008. Patients were divided into two groups. Group 1 consisted
      of 11 patients who had positive results in skin prick test or whose positivity of
      allergy was confirmed by serum-specific immunoglobulin E, as a skin prick test
      was contraindicated. Group 2 included 18 patients who had negative allergy test
      results. Endoscopic and radiological evaluations of the patients were done
      preoperatively. Bilateral endoscopic sinus surgery was applied to all patients.
      RESULTS: Statistical analysis of pre- and postoperative endoscopic and
      radiological evaluation findings in group 1 showed a non-significant improvement
      (p>0.05). Statistical analysis of pre- and postoperative endoscopic and
      radiological evaluation findings in group 2 demonstrated a significant
      improvement (p<0.001, p<0.005 respectively). CONCLUSION: Response to surgical
      treatment is more limited in nasal polyposis patients with a positive allergy
      test.

PMID- 25046068
TI  - Effects of nasal pack use on surgical success in septoplasty.
AB  - OBJECTIVES: This study aims to evaluate the effects of nasal packs on surgical
      success and related complications in septoplasty. PATIENTS AND METHODS: Thirty
      eight patients (21 males, 17 females; mean age, 36.6 years, range 18 to 61 years)
      were included in the study. Septoplasty candidates were prospectively divided
      into two groups. Nasal packing and transseptal suture technique was applied to
      patients in group 1 (n=16) and group 2 (n=22), respectively. Postoperative pain
      was assessed with the visual analog scale. The success of surgery was questioned
      using the Nasal Obstruction Septoplasty Effectiveness (NOSE) scale. Surgical
      success was defined as a 50% decrease in the NOSE scores. RESULTS: There was no
      statistically significant difference in surgical success and complication rates
      between the groups (p>0.05). Pain scores were significantly higher in group 1
      (p=0.015). CONCLUSION: Our study results suggest that nasal pack use does not
      affect surgical success and complication rates in septoplasty. Pack-free
      septoplasty with the transseptal suture technique is an effective method in the
      treatment of septal deviation.

PMID- 25046069
TI  - Epistaxis management: is medical intervention required for inactive epistaxis?
AB  - OBJECTIVES: This study aims to discuss the management and the follow-up approach
      in patients with epistaxis. PATIENTS AND METHODS: A total of 367 patients with
      epistaxis (209 males, 158 females; mean age 52.6+/-18.3 years; range 18 to 85
      years) admitted to the Adult Emergency Department of a university hospital
      between January 2000 and December 2004 were retrospectively analyzed. RESULTS: Of
      patients, 56.7% had an idiopathic bleeding. A significantly higher number of
      patients aged >50 years had high blood pressure on admission. Of 141 patients
      (38.49%) presenting without bleeding on admission, 20 required medical
      intervention for recurrent epistaxis. Conservative approaches were effective in
      stopping bleeding in 97.8% patients. The hospitalization ratio was 5.7%.
      CONCLUSION: Our study result show that endonasal endoscopic mucosal cauterization
      is an effective method for resistant-to-treatment cases and inactive bleeding on
      admission is not a restraint for further examination.

PMID- 25046070
TI  - Quality of life in patients with persistent allergic rhinitis treated with
      desloratadine monotherapy or desloratadine plus montelucast combination.
AB  - OBJECTIVES: This study aims to compare the effectiveness of desloratadine
      monotherapy and desloratadine plus montelukast combination therapy on quality of
      life in patients with persistent allergic rhinitis. PATIENTS AND METHODS: This
      study consists of 40 patients (28 females, 12 males, mean age 29.8 years; range
      17 to 44 years) referred to ear, nose, and throat outpatient clinic between May
      2010 and September 2010. A six-week randomized, double-blind, cross-sectional
      study was performed in two arms: In group 1, 20 patients received desloratadine
      (5 mg/d) alone; in group 2, 20 patients received desloratadine (5 mg) plus
      montelukast (10 mg) combination therapy. Quality of life was assessed on the day
      before starting treatment and on the last day of each treatment period using the
      Rhinoconjunctivitis Quality of Life Questionnaire and Nighttime Symptom Scores.
      RESULTS: In group 1, the mean quality of life scores before and after treatment
      were 3.17 and 2.43, respectively. In group 2, the mean quality of life scores
      before and after treatment were 2.94 and 1.73, respectively. CONCLUSION:
      Desloratadine plus montelukast combination therapy may have a positive impact on
      quality of life, sleep symptoms in particular.

PMID- 25046071
TI  - [Primary intraosseous squamous cell carcinoma of the mandible].
AB  - Primary intraosseous squamous cell carcinoma is an extremely rare tumor of the
      mandible. The diagnosis is based on the evidences showing that the tumor is
      neither originated from a distant metastasis of another primary tumor nor an
      invasive oral cancer. In this article, we report a 59-year-old female case with a
      medical history of ductal carcinoma of the breast, lichen planus, and rheumatoid
      arthritis who was admitted with complaints of a painful and swollen left lower
      jaw, and was surgically treated for primary intraosseous carcinoma of the
      mandible and with postoperative adjuvant radiotherapy. 

PMID- 25046072
TI  - [The same nasal tip deformity in three siblings].
AB  - Similar to all other system anomalies, congenital nasal anomalies are caused by
      the defects during embriyogenesis and organogenesis. Nasal tip anomalies are
      usually accompanied by other systemic pathologies and syndromes. In this article,
      we report a nose anomaly with the same nasal tip appearance in three siblings. 

PMID- 25046073
TI  - [Unfavorable sialoblastoma: a rare case].
AB  - Sialoblastoma is an extremely rare tumor of childhood. It is commonly presented
      as a mass of parotid gland and submandibular gland. In this article, we report a
      recurrent unfavorable sialoblastoma in four-year-old boy. 

PMID- 25046074
TI  - [Sinonasal teratocarcinosarcoma].
AB  - Sinonasal teratocarcinosarcoma is an extremely rare malignant neoplasm presenting
      with the characteristics of a malignant teratoma and carcinosarcoma. The most
      common sites of origin of teratocarcinosarcomas are the nasal cavity and
      paranasal sinuses. The clinical presentation is usually with nasal obstruction
      and episodes of epistaxis. Teratocarcinosarcomas are aggressive and rapidly
      growing tumors with a poor prognosis. The incidence of sinonasal teratocarcinomas
      is higher in men than women. Treatment is primarily surgery, followed by
      radiotherapy. In this article, we report a 46-year-old male case of sinonasal
      teratocarcinosarcoma who was admitted with complaints of pain and swelling around
      the right eye and treated surgically followed by radiotherapy. 

PMID- 25046075
TI  - [Peripheral ossifying fibroma of maxilla].
AB  - Peripheral ossifying fibromas are rare pathologies characterized by the
      replacement of bone to fibrous tissue. In this article, we report a 64-year-old
      female case admitted to our clinic with a mass in the oral cavity for 10 years.
      On physical examination, a 5x4 cm, well-defined, pedunculated mass was detected
      in the anterior arch of the right maxilla. Based on the clinical, radiographic
      and histopathological findings, the mass was diagnosed as an ossifying fibroma. 

PMID- 25046076
TI  - Ionic liquids based on phosphonium cations as neat lubricants or lubricant
      additives for a steel/steel contact.
AB  - After doing several miscibility essays with eight ionic liquids (ILs) and four
      base oils, the ILs tri(butyl)ethylphosphonium diethylphosphate
      [P4,4,4,2][C2C2PO4] and trihexyl(tetradecyl)phosphonium
      tris(pentafluoroethyl)trifluorophosphate [P6,6,6,14][(C2F5)3PF3] were selected to
      be studied as lubricant additives. The neat IL [P4,4,4,2][C2C2PO4], the base
      oils, and several blends were characterized in terms of density, viscosity, and
      thermal stability. The tribological performance of the miscible base oil/IL
      blends (1 wt %) and the neat [P4,4,4,2][C2C2PO4] were evaluated for the
      lubrication of an AISI 420 steel-100Cr6 steel contact pair. The friction
      coefficients and wear volumes obtained are also compared with those corresponding
      to the pure base oils and their mixtures with conventional additive zinc
      dialkyldithiophosphate (ZDDP). As neat lubricants, [P4,4,4,2][C2C2PO4] showed the
      best antifriction ability, whereas in terms of wear, better results were obtained
      with [P6,6,6,14][(C2F5)3PF3]. However, higher improvements in both friction and
      wear were found for blends containing [P4,4,4,2][C2C2PO4]. XPS analyses of the
      worn surfaces lubricated with these mixtures indicated the presence of phosphorus
      in the tribofilm formed on the wear track. However, this compound was slightly
      detected on tribosamples lubricated with blends containing
      [P6,6,6,14][(C2F5)3PF3]. 

PMID- 25046077
TI  - Mid-infrared spectral characteristics of lipid molecular structures in Brassica
      carinata seeds: relationship to oil content, fatty acid and glucosinolate
      profiles, polyphenols, and condensed tannins.
AB  - The objectives of this study were to quantify lipid-related inherent molecular
      structures using a Fourier transform infrared spectroscopy (FT-IR) technique and
      determine their relationship to oil content, fatty acid and glucosinolate
      profile, total polyphenols, and condensed tannins in seeds from newly developed
      yellow-seeded and brown-seeded Brassica carinata lines. Canola seeds were used as
      a reference. The lipid-related molecular spectral band intensities were strongly
      correlated to the contents of oil, fatty acids, glucosinolates, and polyphenols.
      The regression equations gave relatively high predictive power for the estimation
      of oil (R2 = 0.99); all measured fatty acids (R2 > 0.80), except C14:0, C20:3n-3,
      C22:2n-9, and C22:2n-6; 3-butenyl, 2-OH-3-butenyl, 4-OH-3-CH3-indolyl, and total
      glucosinolates (R2 > 0.686); and total polyphenols (R2 = 0.935). However, further
      study is required to obtain predictive equations based on large numbers of
      samples from diverse sources to illustrate the general applicability of these
      regression equations.

PMID- 25046078
TI  - Vitamin B12 derivatives for orthogonal functionalization.
AB  - The synthesis of vitamin B12 derivatives for selective orthogonal conjugation at
      both the Co center and 5'-OH is reported. Newly developed, reduction-free, direct
      alkynylation of vitamin B12 at the central cobalt ion proved to be versatile,
      with the formed acetylides, unlike other metalloorganic derivatives, showing
      remarkable heat and light stability, thus making them promising candidates as a
      drug carrier. Subsequently, high-yielding functionalization can be achieved via a
      sequence of selective [1,3] dipolar azide-alkyne cycloadditions (AACs) or
      carbamate formation followed by AAC. 

PMID- 25046079
TI  - Serum cystatin C and serum and urine NGAL in the kidney function assessment of
      patients with MGUS.
AB  - OBJECTIVES: Monoclonal gammopathy of undetermined significance (MGUS) occurs
      without other symptoms, although monoclonal proteins can cause kidney injuries.
      Here, we assessed kidney function and identified the best follow-up parameters in
      patients with MGUS without kidney damage symptoms. METHODOLOGY: Forty-six
      patients with MGUS were included in the study group. The control group (CRT, n =
      23) consisted of healthy subjects matched for age and sex. Serum cystatin C was
      determined using an immunonephelometric method, serum and urine neutrophil
      gelatinase-associated lipocalin (NGAL) was measured with an immunoenzymatic
      method, and cathepsin B activity was determined fluorometrically. RESULTS: Serum
      cystatin C and urine NGAL were higher, and serum NGAL was lower in MGUS patients
      compared with CRT. Neither serum cystatin C, nor serum or urine NGAL, correlated
      with the biomarkers of MGUS. The serum activity of cathepsin B did not differ
      between groups and did not correlate with serum cystatin C. Serum cystatin C
      correlated with serum creatinine, while serum NGAL did not correlate with serum
      creatinine or cystatin C. The estimated glomerular filtration rates (eGFRs) in
      MGUS were within normal range and correlated with serum cystatin C. The strongest
      correlation was observed for CKD-EPI. Seven patients presented with albuminuria
      >30 mg/day. There was a correlation between albuminuria in this group and lambda
      free light chains. CONCLUSIONS: The kidney function in MGUS patients is impaired,
      although there are no clinical and standard laboratory test manifestations.
      Cystatin C and urine, but not serum, NGAL should be considered markers for kidney
      injury. CKD-EPI is recommended for eGFR assessment.

PMID- 25046080
TI  - The role of religion and spirituality in mental health.
AB  - PURPOSE OF REVIEW: There has been increased interest in the relationship between
      religion and spirituality and mental health in recent years. This article reviews
      recent research into the capacity of religion and spirituality to benefit or harm
      the mental health of believers. We also examine the implications this may have
      for assessment and treatment in psychiatric settings. RECENT FINDINGS: Studies
      indicate that religion and spirituality can promote mental health through
      positive religious coping, community and support, and positive beliefs. Research
      also shows that religion and spirituality can be damaging to mental health by
      means of negative religious coping, misunderstanding and miscommunication, and
      negative beliefs. Tools for the assessment of patients' spiritual needs have been
      studied, and incorporation of spiritual themes into treatment has shown some
      promise. SUMMARY: Religion and spirituality have the ability to promote or damage
      mental health. This potential demands an increased awareness of religious matters
      by practitioners in the mental health field as well as ongoing attention in
      psychiatric research.

PMID- 25046081
TI  - Understanding and translating the knowledge about placebo effects: the
      contribution of psychology.
AB  - PURPOSE OF REVIEW: Recent articles have summarized the literature on the
      neurobiological mechanisms involved in placebo effects. In this article, we
      review and evaluate the status of the psychological mechanisms in theory and
      research regarding placebo effects. RECENT FINDINGS: Currently, the placebo
      effect literature concentrates more on neurobiological mechanisms than on
      psychological mechanisms. Both theoretical and empirical coverage of the
      psychological mechanisms are typically limited to two variables: conditioning and
      verbally induced expectations. Because psychological processes take center stage
      in mediating the link between the therapeutic context and placebo responding,
      greater effort is needed to build empirically derived and theoretically complex
      psychological process models. Such models would include a broader array of
      psychological constructs and mechanisms. SUMMARY: Research and theory on placebo
      effects has illuminated much regarding the neurobiological mechanisms. The
      psychological mechanisms, however, have received much less attention. Expanding
      our knowledge regarding the psychological processes involved in placebo
      responding would open up opportunities for developing nondeceptive intervention
      techniques that encourage placebo responses. Ultimately, a concerted empirical
      effort to clarify the psychological model underlying placebo effects could merge
      with the evolving neurobiological model to fulfill the promise that placebo
      effects have for improving patient outcomes.

PMID- 25046082
TI  - Removal of paralytic shellfish toxins by probiotic lactic acid bacteria.
AB  - Paralytic shellfish toxins (PSTs) are non-protein neurotoxins produced by
      saltwater dinoflagellates and freshwater cyanobacteria. The ability of
      Lactobacillus rhamnosus strains GG and LC-705 (in viable and non-viable forms) to
      remove PSTs (saxitoxin (STX), neosaxitoxin (neoSTX), gonyautoxins 2 and 3
      (GTX2/3), C-toxins 1 and 2 (C1/2)) from neutral and acidic solution (pH 7.3 and
      2) was examined using HPLC. Binding decreased in the order of STX ~ neoSTX > C2 >
      GTX3 > GTX2 > C1. Removal of STX and neoSTX (77%-97.2%) was significantly greater
      than removal of GTX3 and C2 (33.3%-49.7%). There were no significant differences
      in toxin removal capacity between viable and non-viable forms of lactobacilli,
      which suggested that binding rather than metabolism is the mechanism of the
      removal of toxins. In general, binding was not affected by the presence of other
      organic molecules in solution. Importantly, this is the first study to
      demonstrate the ability of specific probiotic lactic bacteria to remove PSTs,
      particularly the most toxic PST-STX, from solution. Further, these results
      warrant thorough screening and assessment of safe and beneficial microbes for
      their usefulness in the seafood and water industries and their effectiveness in
      vivo. 

PMID- 25046083
TI  - The free volume in dried and H2O-loaded biopolymers studied by positron lifetime
      measurements.
AB  - We present experiments on glucose-gelatin compounds using positron annihilation
      lifetime spectroscopy (PALS) in order to study the behavior of the free volume
      dependent on H2O loading, drying, and uniaxial pressure. A semiempirical quantum
      mechanical model was applied in order to correlate the lifetime of
      orthopositronium in nanoscaled voids to the void size. This allowed us to
      determine the absolute value of the mean void radius in the biopolymer samples.
      In addition, the variation of the total free volume of the differently treated
      samples is quantified and illustrated by a log-normal distribution function. Most
      interesting results have been obtained after saturation loading with H2O that
      leads to the formation of voids with a mean size of 84.3(1.9) A(3) and to an
      increase of the total free volume by a factor of 2.5. This observation in the
      swelled sample is explained by the entropy elastic regime well above the glass
      transition temperature that greatly facilitates the formation of free volume.
      Differential scanning calorimetry (DSC) measurements were performed in order to
      determine the glass transition temperature and to support the interpretation of
      the results obtained by PALS. 

PMID- 25046084
TI  - Tar Heel footprints in health care: Tami Kittrell.

PMID- 25046085
TI  - Health care utilization from chemotherapy-related adverse events among low-income
      breast cancer patients: effect of enrollment in a medical home program.
AB  - BACKGROUND: Chemotherapy-related health care utilization by breast cancer
      patients can be expensive for payers and patients. This study evaluated the
      patient-centered medical home program Community Care of North Carolina (CCNC) in
      terms of its potential to reduce health care utilization associated with
      chemotherapy-related adverse events (AEs). METHODS: Early-stage breast cancer
      cases diagnosed during the 5-year period 2003-2007 were identified in the North
      Carolina Central Cancer Registry; these cases were then linked to North Carolina
      Medicaid claims data. We measured health care utilization associated with
      chemotherapy-related AEs by setting (inpatient, outpatient, or emergency
      department) during a 15-month postdiagnosis follow-up period. Descriptive and
      multivariate analyses were performed to examine associations between CCNC
      enrollment and health care utilization associated with chemotherapy-related AEs.
      RESULTS: A large proportion of breast cancer patients had at least 1 health care
      visit associated with a chemotherapy-related AE (n = 412 [72.3%]). The mean
      numbers of AE-related visits occurring in inpatient, outpatient, and emergency
      department settings were 0.30 (standard deviation [SD] = 0.83), 6.92 (SD =
      10.94), and 0.46 (SD = 1.26), respectively. CCNC enrollment was associated with
      significantly fewer inpatient admissions (marginal effect, -0.1421; 95%
      confidence interval, -0.280 to -0.004). LIMITATIONS: In this observational study,
      we were unable to draw conclusions about the causality of these associations.
      CONCLUSIONS: Patients enrolled in CCNC had fewer inpatient health care visits
      associated with chemotherapy-related AEs. Future research should continue to
      explore the extent to which patient-centered medical homes can monitor and help
      manage the effects of cancer treatments.

PMID- 25046086
TI  - Effects of distance to care and rural or urban residence on receipt of radiation
      therapy among North Carolina Medicare enrollees with breast cancer.
AB  - BACKGROUND: Distance to oncology service providers and rurality may affect
      receipt of guideline-recommended radiation therapy (RT), but the extent to which
      these factors affect the care of Medicare-insured patients is unknown. METHODS:
      Using cancer registry data linked to Medicare claims from the Integrated Cancer
      Information and Surveillance System (ICISS), we identified all women aged 65
      years or older who were diagnosed with stage I, II, or III breast cancer from
      2003 through 2005, who had Medicare claims through 2006, and who were clinically
      eligible for RT. We geocoded the address of each RT service provider's practice
      location and calculated the travel distance from each patient's residential
      address to the nearest RT provider. We used ZIP codes to classify each patient's
      residence as rural or urban according to rural- urban commuting area codes. We
      used generalized estimating equations models with county-level clustering and
      interaction terms between distance categories and rural-urban status to estimate
      the effect of distance to care and rural-urban status on receipt of RT. RESULTS:
      In urban areas, increasing distance to the nearest RT provider was associated
      with a lower likelihood of receiving RT (odds ratio [OR] = 0.54; 95% confidence
      interval [CI], 0.30-0.97) for those living more than 20 miles from the nearest RT
      provider compared with those living less than 10 miles away. In rural areas,
      those living within 10-20 miles of the nearest RT provider were more likely to
      receive RT than those living less than 10 miles away (OR = 1.73; 95% CI, 1.08
      2.76). LIMITATIONS: Results may not be generalizable to areas outside North
      Carolina or to non-Medicare populations. CONCLUSION: Coordinated outreach
      programs targeted differently to rural and urban patients may be necessary to
      improve the quality of oncology care.

PMID- 25046087
TI  - Pushing back against the long shadow of cancer.

PMID- 25046088
TI  - Cancer care research in North Carolina: the state of the state.
AB  - Cancer is the leading cause of death in North Carolina. This issue brief
      summarizes cancer statistics for the state; highlights important issues facing
      cancer patients, caregivers, providers, and policy makers; discusses the state's
      novel resources for cancer care research; and explores ways of managing this
      public health problem in order to improve outcomes for the people of North
      Carolina. 

PMID- 25046089
TI  - Controversies in cancer screening.
AB  - New studies raise concerns about whether screening for some cancers may cause
      more harm than good. This commentary reviews evidence relevant to current
      controversies in cancer screening, highlights why it is so difficult to formulate
      universal screening recommendations, and emphasizes the importance of informed
      and shared decision making. 

PMID- 25046090
TI  - Obstacles to affordable cancer treatments.
AB  - Recent regulatory and policy changes may help to improve the affordability of
      some high-cost cancer treatments. However, larger systemic changes are needed to
      address the excessive growth in spending for cancer therapies and to ensure that
      patients and payers receive maximum value for their health care dollars. 

PMID- 25046091
TI  - Speeding the dissemination and implementation of evidence-based interventions for
      cancer control and prevention.
AB  - Despite the growing menu of evidence-based interventions to prevent and control
      cancer, such interventions continue to be underused in practice. This commentary
      describes interactive approaches to speeding the dissemination and implementation
      of evidence-based interventions and illustrates these approaches using examples
      from obesity prevention and tobacco control. 

PMID- 25046092
TI  - Big data for population-based cancer research: the integrated cancer information
      and surveillance system.
AB  - The Integrated Cancer Information and Surveillance System (ICISS) facilitates
      population-based cancer research by developing extensive information technology
      systems that can link and manage large data sets. Taking an interdisciplinary
      'team science' approach, ICISS has developed data, systems, and methods that
      allow researchers to better leverage the power of big data to improve population
      health. 

PMID- 25046093
TI  - The ethics of clinical trials for cancer therapy.
AB  - Cancer clinical trials are intended to evaluate novel interventions and to
      improve outcomes. Such research depends on the participation of patients seeking
      the best options for care. The design, conduct, and analysis of trials must
      therefore be grounded in an ethical framework that respects and protects the
      interests of clinical trial participants. 

PMID- 25046094
TI  - Expanding use of palliative care in the oncology setting.
AB  - The use of palliative care for patients with serious disease improves quality of
      life, reduces symptoms, and saves money. Unfortunately, too many patients endure
      needless suffering. Expanding awareness about palliative care among patients,
      providers, and policymakers will hopefully generate momentum for use of such
      services, thus benefitting patients with cancer and other advanced diseases. 

PMID- 25046095
TI  - Pediatric oncology and palliative care.

PMID- 25046096
TI  - Living with advanced cancer: unmet survivorship needs.
AB  - Most cancer survivorship initiatives are designed for patients whose treatment is
      intended to be curative. For patients living with advanced cancer, in contrast,
      survivorship research efforts and programs are far less common. This neglected
      aspect of cancer survivorship requires particular emphasis on active symptom
      management and clarification of goals of care. 

PMID- 25046098
TI  - Cancer in a 29-county area in eastern North Carolina: an opportunity to reduce
      health inequities.
AB  - Cancer mortality rates are higher in a 29-county area of Eastern North Carolina
      than in the state's other 71 counties combined; within this 29-county subregion,
      African Americans have higher cancer mortality rates than whites. Better
      integration of health promotion and structural changes that improve health care
      access and delivery are needed to reduce these disparities. 

PMID- 25046099
TI  - Gynecologic cancers: incidence and mortality trends among women in North
      Carolina.

PMID- 25046097
TI  - Physical and mental health among cancer survivors: considerations for long-term
      care and quality of life.
AB  - The physical and mental health of cancer patients needs to be addressed not only
      during active treatment but also throughout the continuum of survivorship care.
      This commentary provides an overview of issues pertinent to cancer survivors,
      with an emphasis on mental health issues and recommendations for annual clinical
      screening and monitoring using recently published guidelines from the American
      Society of Clinical Oncology. 

PMID- 25046100
TI  - The V Foundation's efforts to support cancer research.

PMID- 25046101
TI  - Solution voltammetry of 4 nm magnetite iron oxide nanoparticles.
AB  - The voltammetry of solution-dispersed magnetite iron oxide Fe3O4 nanoparticles is
      described. Their currents are controlled by nanoparticle transport rates, as
      shown with potential step chronoamperometry and rotated disk voltammetry. In pH 2
      citrate buffer with added NaClO4 electrolyte, solution cyclic voltammetry of
      these nanoparticles (average diameter 4.4 +/- 0.9 nm, each containing ca. 30 Fe
      sites) displays an electrochemically irreversible oxidation with E(PEAK) at ca.
      +0.52 V and an irreversible reduction with E(PEAK) at ca. +0.2 V vs Ag/AgCl
      reference electrode. These processes are presumed to correspond to the formal
      potentials for one-electron oxidation of Fe(II) and reduction of Fe(III) at their
      different sites in the magnetite nanoparticle structure. The heterogeneous
      electrode reaction rates of the nanoparticles are very slow, in the 10(-5) cm/s
      range. The nanoparticles are additionally characterized by a variety of tools,
      e.g., TEM, UV/vis, and XPS spectroscopies.

PMID- 25046102
TI  - Microcirculation density and maturity in uterine and soft tissue leiomyosarcomas:
      an immunohistochemical study.
AB  - The role of angiogenesis as a hallmark of tumor progression has been poorly
      explored in leiomyosarcoma, a rare but aggressive mesenchymal malignancy. We
      aimed to characterize microvessel distribution and morphology - including
      pericyte coverage - in a retrospective series of leyomiosarcomas of the soft
      tissues and the uterus. 41 whole-block tumor slides from formalin-fixed paraffin
      embedded tissues were immunostained for endothelial-specific marker CD31 and
      microvessel density was quantified by assigning a grade to the frequency of CD31
      positive microvessels. Vessel morphology and pericyte coverage were investigated
      by double-labeling for CD31 and either PDGFRbeta, alphaSMA, desmin, CD90, or
      CD146. We found that microvessel density correlated with tumor grade in
      leiomyosarcoma of soft tissues, in analogy with what has been established in
      several types of carcinoma. This did not apply to uterine leiomyosarcoma,
      possibly due to the abundant myometrial vascularization. The evaluation of
      perivascular cell markers related to vessel stability revealed immature
      microvascular networks with aberrant pericyte coverage, irrespective of tumor
      origin or grade. Our observations substantiate the role of angiogenesis in the
      progression of soft tissue leiomyosarcoma. A multiple-marker approach to the
      assessment of pericyte coverage can identify different profiles of vessel
      immaturity correlated with tumor grade.

PMID- 25046104
TI  - Rational targeting of subclasses of intermolecular interactions: elimination of
      nonspecific binding for analyte sensing.
AB  - The ability to target and control intermolecular interactions is crucial in the
      development of several different technologies. Here we offer a tool to rationally
      design liquid media systems that can modulate specific intermolecular
      interactions. This has broad implications in deciphering the nature of
      intermolecular forces in complex solutions and offers insight into the forces
      that govern both specific and nonspecific binding in a given system. Nonspecific
      binding still continues to be a problem when dealing with analyte detection
      across a range of different detection technologies. Here, we exemplify the
      problem of nonspecific binding on model membrane systems and when dealing with
      low-abundance protein detection on commercially available SPR technology. A range
      of different soluble reagents that target specific subclasses of intermolecular
      interactions have been tested and optimized to virtually eliminate nonspecific
      binding while leaving specific interactions unperturbed. Thiocyanate ions are
      used to target nonpolar interactions, and small reagents such as
      glycylglycylglycine are used to modulate the dielectric constant, which targets
      charge-charge and dipole interactions. We show that with rational design and
      careful modulation these reagents offer a step forward in dissecting the
      intermolecular forces that govern binding, alongside offering nonspecific binding
      elimination in detection systems. 

PMID- 25046103
TI  - Application of two-spotted spider mite Tetranychus urticae for plant-pest
      interaction studies.
AB  - The two-spotted spider mite, Tetranychus urticae, is a ubiquitous polyphagous
      arthropod herbivore that feeds on a remarkably broad array of species, with more
      than 150 of economic value. It is a major pest of greenhouse crops, especially in
      Solanaceae and Cucurbitaceae (e.g., tomatoes, eggplants, peppers, cucumbers,
      zucchini) and greenhouse ornamentals (e.g., roses, chrysanthemum, carnations),
      annual field crops (such as maize, cotton, soybean, and sugar beet), and in
      perennial cultures (alfalfa, strawberries, grapes, citruses, and plums)1,2. In
      addition to the extreme polyphagy that makes it an important agricultural pest,
      T. urticae has a tendency to develop resistance to a wide array of insecticides
      and acaricides that are used for its control3-7. T. urticae is an excellent
      experimental organism, as it has a rapid life cycle (7 days at 27  degrees C) and
      can be easily maintained at high density in the laboratory. Methods to assay gene
      expression (including in situ hybridization and antibody staining) and to
      inactivate expression of spider mite endogenous genes using RNA interference have
      been developed8-10. Recently, the whole genome sequence of T. urticae has been
      reported, creating an opportunity to develop this pest herbivore as a model
      organism with equivalent genomic resources that already exist in some of its host
      plants (Arabidopsis thaliana and the tomato Solanum lycopersicum)11. Together,
      these model organisms could provide insights into molecular bases of plant-pest
      interactions. Here, an efficient method for quick and easy collection of a large
      number of adult female mites, their application on an experimental plant host,
      and the assessment of the plant damage due to spider mite feeding are described.
      The presented protocol enables fast and efficient collection of hundreds of
      individuals at any developmental stage (eggs, larvae, nymphs, adult males, and
      females) that can be used for subsequent experimental application.

PMID- 25046105
TI  - Targeting HER3 with miR-450b-3p suppresses breast cancer cells proliferation.
AB  - In breast cancer cells, heterodimerization of HER2 and HER3 plays important and
      dominant roles in the functionality and transformation of HER-mediated pathways,
      in particular the PI3K/Akt survival pathway. HER3 was considered as a major
      signaling hub in HER2-amplified cancers. Inhibition of HER3 expression may
      therefore represent a rational therapeutic approach to breast cancers where
      HER2/HER3-mediated signaling plays a role in tumorigenesis and progression.
      miRNAs exerts important roles in regulating gene expressions by binding to and
      repressing target mRNAs. Here we reported that miRNA-450b-3p inhibits HER3
      expression by directly targeting 3' UTR of HER3 mRNA and represses the downstream
      signal transductions of HER family. Overexpression of miRNA-450b-3p in SKBR3
      cells inhibits cells clonogenic potential and enhances their sensitivity to
      trastuzumab, a monoclonal antibody that binds to the HER2 receptor, or
      doxorubicin through repressing proliferative signal pathways mediated by
      HER3/HER2/PI3K/AKT. Furthermore, we found that breast cancer patients with tumors
      that demonstrating upregulated HER3 (> 2-fold) and downregulated miR-450b-3p (> 2
      fold) expressions compared with the paired adjacent non-tumorous tissues showed
      significantly poorer overall survival (P<0.05). Our study identified miRNA-450b
      3p as a new tumor repressor and also provided some evidences suggesting that
      downregulation of miR-450b-3p expression with concurrent overexpression of HER3
      may serve as a prognostic biomarker for poor overall survival in breast cancer
      patients. 

PMID- 25046106
TI  - Fermentable non-starch polysaccharides increases the abundance of Bacteroides
      Prevotella-Porphyromonas in ileal microbial community of growing pigs.
AB  - Most plant-origin fiber sources used in pig production contains a mixture of
      soluble and insoluble non-starch polysaccharides (NSP). The knowledge about
      effects of these sources of NSP on the gut microbiota and its fermentation
      products is still scarce. The aim of this study was to investigate effects of
      feeding diets with native sources of NSP on the ileal and fecal microbial
      composition and the dietary impact on the concentration of short-chain fatty
      acids (SCFA) and lactic acid. The experiment comprised four diets and four
      periods in a change-over design with seven post valve t-cecum cannulated growing
      pigs. The four diets were balanced to be similar in NSP content and included one
      of four fiber sources, two diets were rich in pectins, through inclusion of
      chicory forage (CFO) and sugar beet pulp, and two were rich in arabinoxylan,
      through inclusion of wheat bran (WB) and grass meal. The gut microbial
      composition was assessed with terminal restriction fragment (TRF) length
      polymorphism and the abundance of Lactobacillus spp., Enterobacteriaceae,
      Bacteroides-Prevotella-Porphyromonas and the beta-xylosidase gene, xynB, were
      assessed with quantitative PCR. The gut microbiota did not cluster based on NSP
      structure (arabinoxylan or pectin) rather, the effect was to a high degree
      ingredient specific. In pigs fed diet CFO, three TRFs related to Prevotellaceae
      together consisted of more than 25% of the fecal microbiota, which is about 3 to
      23 times higher (P<0.05) than in pigs fed the other diets. Whereas pigs fed diet
      WB had about 2 to 22 times higher abundance (P<0.05) of Megasphaera elsdenii in
      feces and about six times higher abundance (P<0.05) of Lactobacillus reuteri in
      ileal digesta than pigs fed the other diets. The total amount of digested NSP
      (r=0.57; P=0.002), xylose (r=0.53; P=0.004) and dietary fiber (r=0.60; P=0.001)
      in ileal digesta were positively correlated with an increased abundance of
      Bacteroides-Prevotella-Porphyromonas. The effect on SCFA was correlated to
      specific neutral sugars where xylose increased the ileal butyric acid proportion,
      whereas arabinose increased the fecal butyric acid proportion. Moreover, chicory
      pectin increased the acetic acid proportion in both ileal digesta and feces. 

PMID- 25046107
TI  - Inhibition of autophagy attenuates pancreatic cancer growth independent of
      TP53/TRP53 status.
AB  - Basal levels of autophagy are elevated in most pancreatic ductal adenocarcinomas
      (PDAC). Suppressing autophagy pharmacologically using chloroquine (CQ) or
      genetically with RNAi to essential autophagy genes inhibits human pancreatic
      cancer growth in vitro and in vivo, which presents possible treatment
      opportunities for PDAC patients using the CQ-derivative hydroxychloroquine (HCQ).
      Indeed, such clinical trials are ongoing. However, autophagy is a complex
      cellular mechanism to maintain cell homeostasis under stress. Based on its
      biological role, a dual role of autophagy in tumorigenesis has been proposed: at
      tumor initiation, autophagy helps maintain genomic stability and prevent tumor
      initiation; while in advanced disease, autophagy degrades and recycles cellular
      components to meet the metabolic needs for rapid growth. This model was proven to
      be the case in mouse lung tumor models. However, in contrast to prior work in
      various PDAC model systems, loss of autophagy in PDAC mouse models with embryonic
      homozygous Trp53 deletion does not inhibit tumor growth and paradoxically
      increases progression. This raised concerns whether there may be a genotype
      dependent reliance of PDAC on autophagy. In a recent study, our group used a
      Trp53 heterozygous mouse PDAC model and human PDX xenografts to address the
      question. Our results demonstrate that autophagy inhibition was effective against
      PDAC tumors irrespective of TP53/TRP53 status. 

PMID- 25046108
TI  - Loss of chloroplast ClpP elicits an autophagy-like response in Chlamydomonas.
AB  - Chloroplast genomes contain a single ClpP1 gene encoding one of the catalytic
      subunits of the evolutionarily conserved ATP-dependent Clp protease. Efforts to
      inactivate this protease in the chloroplast through targeted disruption of the
      clpP1 gene have failed, suggesting that it is essential for cell survival in
      plants. To circumvent this problem, a repressible chloroplast gene expression
      system was developed in the green unicellular alga Chlamydomonas reinhardtii.
      This system takes advantage of the nuclear Nac2 gene fused to the MetE promoter
      and Thi4 riboswitch, which can be repressed by adding vitamin B12 and thiamine to
      the growth medium. Nac2 encodes a chloroplast protein that interacts specifically
      with the 5'UTR of the psbD mRNA and is involved in processing/translation of this
      transcript. Loss of Nac2 leads to the specific degradation of psbD mRNA. Because
      the psbD 5'UTR is necessary and sufficient for the Nac2-dependent stability of
      psbD mRNA, this dependence can be transferred to any chloroplast gene by linking
      its coding sequence to the psbD 5 'UTR. In this way it was possible to repress
      the clpP1 gene in a reversible way with vitamins. 

PMID- 25046109
TI  - Transcriptional regulation of ATG9 by the Pho23-Rpd3 complex modulates the
      frequency of autophagosome formation.
AB  - Studies of the physiological and pathological roles of autophagy have revealed
      that too little or too much autophagy can be detrimental, and therefore autophagy
      activity needs to be tightly regulated. Altered transcription of autophagy
      related (ATG) genes has been reported in many diseases, and ATG genes can be the
      most direct targets for the treatment of autophagy-associated diseases. Thus, it
      is important to understand how the amounts of different Atg proteins affect
      autophagy, and how the expression of their corresponding genes is regulated.
      Using budding yeast as the model, we showed that Pho23, a component of the Rpd3
      large (Rpd3L) complex, represses the transcription of several ATG genes including
      ATG9, the expression of which regulates the frequency of autophagosome formation.
      More autophagosomes are formed in PHO23 null cells or in those overexpressing
      Atg9; conversely, there are fewer autophagosomes seen in cells with reduced Atg9
      expression. 

PMID- 25046110
TI  - Autophagy-inducing peptides from mammalian VSV and fish VHSV rhabdoviral G
      glycoproteins (G) as models for the development of new therapeutic molecules.
AB  - It has not been elucidated whether or not autophagy is induced by rhabdoviral G
      glycoproteins (G) in vertebrate organisms for which rhabdovirus infection is
      lethal. Our work provides the first evidence that both mammalian (vesicular
      stomatitis virus, VSV) and fish (viral hemorrhagic septicemia virus, VHSV, and
      spring viremia carp virus, SVCV) rhabdoviral Gs induce an autophagic antiviral
      program in vertebrate cell lines. The transcriptomic profiles obtained from
      zebrafish genetically immunized with either Gsvcv or Gvhsv suggest that autophagy
      is induced shortly after immunization and therefore, it may be an important
      component of the strong antiviral immune responses elicited by these viral
      proteins. Pepscan mapping of autophagy-inducing linear determinants of Gvhsv and
      Gvsv showed that peptides located in their fusion domains induce autophagy.
      Altogether these results suggest that strategies aimed at modulating autophagy
      could be used for the prevention and treatment of rhabdoviral infections such as
      rabies, which causes thousands of human deaths every year. 

PMID- 25046111
TI  - MAPK14/p38alpha-dependent modulation of glucose metabolism affects ROS levels and
      autophagy during starvation.
AB  - Increased glycolytic flux is a common feature of many cancer cells, which have
      adapted their metabolism to maximize glucose incorporation and catabolism to
      generate ATP and substrates for biosynthetic reactions. Indeed, glycolysis allows
      a rapid production of ATP and provides metabolic intermediates required for
      cancer cells growth. Moreover, it makes cancer cells less sensitive to
      fluctuations of oxygen tension, a condition usually occurring in a newly
      established tumor environment. Here, we provide evidence for a dual role of
      MAPK14 in driving a rearrangement of glucose metabolism that contributes to
      limiting reactive oxygen species (ROS) production and autophagy activation in
      condition of nutrient deprivation. We demonstrate that MAPK14 is phosphoactivated
      during nutrient deprivation and affects glucose metabolism at 2 different levels:
      on the one hand, it increases SLC2A3 mRNA and protein levels, resulting in a
      higher incorporation of glucose within the cell. This event involves the MAPK14
      mediated enhancement of HIF1A protein stability. On the other hand, MAPK14
      mediates a metabolic shift from glycolysis to the pentose phosphate pathway (PPP)
      through the modulation of PFKFB3 (6-phosphofructo-2-kinase/fructose 2,6
      bisphosphatase 3) degradation by the proteasome. This event requires the presence
      of 2 distinct degradation sequences, KEN box and DSG motif Ser273, which are
      recognized by 2 different E3 ligase complexes. The mutation of either motif
      increases PFKFB3 resistance to starvation-induced degradation. The MAPK14-driven
      metabolic reprogramming sustains the production of NADPH, an important cofactor
      for many reduction reactions and for the maintenance of the proper intracellular
      redox environment, resulting in reduced levels of ROS. The final effect is a
      reduced activation of autophagy and an increased resistance to nutrient
      deprivation. 

PMID- 25046112
TI  - Japanese encephalitis virus replication is negatively regulated by autophagy and
      occurs on LC3-I- and EDEM1-containing membranes.
AB  - Autophagy is a lysosomal degradative pathway that has diverse physiological
      functions and plays crucial roles in several viral infections. Here we examine
      the role of autophagy in the life cycle of JEV, a neurotropic flavivirus. JEV
      infection leads to induction of autophagy in several cell types. JEV replication
      was significantly enhanced in neuronal cells where autophagy was rendered
      dysfunctional by ATG7 depletion, and in Atg5-deficient mouse embryonic
      fibroblasts (MEFs), resulting in higher viral titers. Autophagy was functional
      during early stages of infection however it becomes dysfunctional as infection
      progressed resulting in accumulation of misfolded proteins. Autophagy-deficient
      cells were highly susceptible to virus-induced cell death. We also observed JEV
      replication complexes that are marked by nonstructural protein 1 (NS1) and dsRNA
      colocalized with endogenous LC3 but not with GFP-LC3. Colocalization of NS1 and
      LC3 was also observed in Atg5 deficient MEFs, which contain only the nonlipidated
      form of LC3. Viral replication complexes furthermore show association with a
      marker of the ER-associated degradation (ERAD) pathway, EDEM1 (ER degradation
      enhancer, mannosidase alpha-like 1). Our data suggest that virus replication
      occurs on ERAD-derived EDEM1 and LC3-I-positive structures referred to as
      EDEMosomes. While silencing of ERAD regulators EDEM1 and SEL1L suppressed JEV
      replication, LC3 depletion exerted a profound inhibition with significantly
      reduced RNA levels and virus titers. Our study suggests that while autophagy is
      primarily antiviral for JEV and might have implications for disease progression
      and pathogenesis of JEV, nonlipidated LC3 plays an important autophagy
      independent function in the virus life cycle. 

PMID- 25046113
TI  - GA binding protein augments autophagy via transcriptional activation of BECN1
      PIK3C3 complex genes.
AB  - Macroautophagy is a vesicular catabolic trafficking pathway that is thought to
      protect cells from diverse stressors and to promote longevity. Recent studies
      have revealed that transcription factors play important roles in the regulation
      of autophagy. In this study, we have identified GA binding protein (GABP) as a
      transcriptional regulator of the combinatorial expression of BECN1-PIK3C3 complex
      genes involved in autophagosome initiation. We performed bioinformatics analyses
      that demonstrated highly conserved putative GABP sites in genes that encode
      BECN1/Beclin 1, several BECN1 interacting proteins, and downstream autophagy
      proteins including the ATG12-ATG5-ATG16L1 complex. We demonstrate that GABP binds
      to the promoter regions of BECN1-PIK3C3 complex genes and activates their
      transcriptional activities. Knockdown of GABP reduced BECN1-PIK3C3 complex
      transcripts, BECN1-PIK3C3 complex protein levels and autophagy in cultured cells.
      Conversely, overexpression of GABP increased autophagy. Nutrient starvation
      increased GABP-dependent transcriptional activity of BECN1-PIK3C3 complex gene
      promoters and increased the recruitment of GABP to the BECN1 promoter. Our data
      reveal a novel function of GABP in the regulation of autophagy via
      transcriptional activation of the BECN1-PIK3C3 complex. 

PMID- 25046114
TI  - Role of VAMP3 and VAMP7 in the commitment of Yersinia pseudotuberculosis to LC3
      associated pathways involving single- or double-membrane vacuoles.
AB  - Yersinia pseudotuberculosis can replicate inside macrophages by hijacking
      autophagy and blocking autophagosome acidification. In bone marrow-derived
      macrophages, the bacteria are mainly observed inside double-membrane vacuoles
      positive for LC3, a hallmark of autophagy. Here, we address the question of the
      membrane traffic during internalization of Yersinia investigating the role of
      vesicle- associated membrane proteins (VAMPs). First, we show that as in
      epithelial cells, Yersinia pseudotuberculosis replicates mainly in nonacidic LC3
      positive vacuoles. Second, in these cells, we unexpectedly found that VAMP3
      localizes preferentially to Yersinia-containing vacuoles (YCVs) with single
      membranes using correlative light-electron microscopy. Third, we reveal the
      precise kinetics of VAMP3 and VAMP7 association with YCVs positive for LC3.
      Fourth, we show that VAMP7 knockdown alters LC3's association with single-and
      multimembrane-YCVs. Finally, in uninfected epithelial cells stimulated for
      autophagy, VAMP3 overexpression and knockdown led respectively to a lower and
      higher number of double-membrane, LC3-positive vesicles. Hence, our results
      highlight the role that VAMPs play in selection of the pathways leading to
      generation of ultrastructurally different LC3 compartments and pave the way for
      determining the full set of docking and fusion proteins involved in Yersinia
      pseudotuberculosis' intravesicular life cycle. 

PMID- 25046115
TI  - BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta:
      implications for a proteasome-to-autophagy switch.
AB  - Eukaryotic cells use autophagy and the ubiquitin-proteasome system as their major
      protein degradation pathways. Upon proteasomal impairment, cells switch to
      autophagy to ensure proper clearance of clients (the proteasome-to-autophagy
      switch). The HSPA8 and HSPA1A cochaperone BAG3 has been suggested to be involved
      in this switch. However, at present it is still unknown whether and to what
      extent BAG3 can indeed reroute proteasomal clients to the autophagosomal pathway.
      Here, we show that BAG3 induces the sequestration of ubiquitinated clients into
      cytoplasmic puncta colabeled with canonical autophagy linkers and markers.
      Following proteasome inhibition, BAG3 upregulation significantly contributes to
      the compensatory activation of autophagy and to the degradation of the
      (poly)ubiquitinated proteins. BAG3 binding to the ubiquitinated clients occurs
      through the BAG domain, in competition with BAG1, another BAG family member, that
      normally directs ubiquitinated clients to the proteasome. Therefore, we propose
      that following proteasome impairment, increasing the BAG3/BAG1 ratio ensures the
      "BAG-instructed proteasomal to autophagosomal switch and sorting" (BIPASS). 

PMID- 25046116
TI  - Autophagy deficiency leads to accumulation of ubiquitinated proteins, ER stress,
      and cell death in Arabidopsis.
AB  - Autophagy is a homeostatic degradation and recycling process that is also
      involved in defense against microbial pathogens and in certain forms of cellular
      suicide. Autophagy has been proposed to negatively regulate plant immunity
      associated cell death related to the hypersensitive response (HR), as older
      autophagy-deficient mutants are unable to contain this type of cell death 5 to 10
      d after infection. Such spreading cell death was found to require NPR1
      (nonexpressor of PR genes 1), but surprisingly did not occur in younger atg
      mutants. In contrast, we find that npr1 mutants are not impaired in rapid
      programmed cell death activation upon pathogen recognition. Furthermore, our
      molecular evidence suggests that the NPR1-dependent spreading cell death in older
      atg mutants may originate from an inability to cope with excessive accumulation
      of ubiquitinated proteins and ER stress which derive from salicylic acid (SA)
      dependent signaling (e.g., systemic acquired resistance). We also demonstrate
      that both senescence and immunity-related cell death seen in older atg mutants
      can be recapitulated in younger atg mutants primed with ER stress. We therefore
      propose that the reduction in SA signaling caused by npr1 loss-of-function is
      sufficient to alleviate the stress levels accumulated during aging in autophagy
      deficient cells which would otherwise become insurmountable and lead to
      uncontrolled cell death. 

PMID- 25046118
TI  - Murine heterotopic heart transplant technique.
AB  - It is now over forty years since this technique was first reported by Corry, Wynn
      and Russell. Although it took some years for other labs to become proficient in
      and utilize this technique, it is now widely used by many laboratories around the
      world. A significant refinement to the original technique was developed and
      reported in 2001 by Niimi. Described here are the techniques that have evolved
      over more than a decade in the hands of three surgeons (Plenter, Grazia, Pietra)
      in our center. These techniques are now being passed on to a younger generation
      of surgeons and researchers. Based largely on the Niimi experience, the
      procedures used have evolved in the fine details - details which we will endeavor
      to relate here in such a way that others may be able to use this very useful
      model. Like Niimi, we have found that a video aid to learning is a priceless
      resource for the beginner. 

PMID- 25046117
TI  - Reciprocal conversion of Gtr1 and Gtr2 nucleotide-binding states by Npr2-Npr3
      inactivates TORC1 and induces autophagy.
AB  - Autophagy is an intracellular degradation process that delivers cytosolic
      material to lysosomes and vacuoles. To investigate the mechanisms that regulate
      autophagy, we performed a genome-wide screen using a yeast deletion-mutant
      collection, and found that Npr2 and Npr3 mutants were defective in autophagy.
      Their mammalian homologs, NPRL2 and NPRL3, were also involved in regulation of
      autophagy. Npr2-Npr3 function upstream of Gtr1-Gtr2, homologs of the mammalian
      RRAG GTPase complex, which is crucial for TORC1 regulation. Both npr2? mutants
      and a GTP-bound Gtr1 mutant suppressed autophagy and increased Tor1 vacuole
      localization. Furthermore, Gtr2 binds to the TORC1 subunit Kog1. A GDP-bound Gtr1
      mutant induced autophagy even under nutrient-rich conditions, and this effect was
      dependent on the direct binding of Gtr2 to Kog1. These results revealed that 2
      molecular mechanisms, Npr2-Npr3-dependent GTP hydrolysis of Gtr1 and direct
      binding of Gtr2 to Kog1, are involved in TORC1 inactivation and autophagic
      induction. 

PMID- 25046119
TI  - CHIPS for genetic testing to improve a regional clinical genetic service.
AB  - In current practice of clinical genetics, molecular diagnosis has become more
      widely used than ever before. DNA diagnosis is important for appropriate medical
      care of the patient, and proper genetic counseling to the family. However,
      genetic testing of orphan disease cannot always be performed easily. In multiple
      congenital anomalies (MCA) syndromes by monogenic cause, the broad mutational
      spectrum and large size of responsible genes often make molecular diagnosis
      expensive and cumbersome. We solve this problem with on-demand genetic testing by
      CHIPS (CEL nuclease mediated heteroduplex incision with polyacrylamide gel
      electrophoresis and silver staining) technology, which is the ultimately
      conventional and economical mutation screening system. In this article, we show
      eight patients with MCA syndromes who were recently treated at our hospital, and
      demonstrate that CHIPS successfully offers efficient and inexpensive genetic
      testing and facilitates clinical genetic service in our local region. 

PMID- 25046120
TI  - Global uptake of the Humanitarian Accountability Partnership over its first ten
      years.
AB  - INTRODUCTION: Accountability in the delivery of humanitarian aid has become
      increasingly important and emphasized by the humanitarian community. The
      Humanitarian Accountability Partnership (HAP) was created in 2003 in order to
      improve accountability in the humanitarian sector. HAP acts as a self-regulatory
      body to the humanitarian system. One of the main goals of HAP is the promotion of
      accountability through self-regulation by members. Humanitarian nongovernmental
      organizations (NGOs) can become members by meeting standards of accountability
      and quality management set by HAP. This report describes the growth of HAP
      membership by the humanitarian community from its inception until present.
      Hypothesis/Problem The hypothesis for this study was that HAP membership has
      grown substantially since inception, both in terms of number of member
      organizations and annual budgets of member organizations, but that near universal
      membership has not yet been achieved. METHODS: A retrospective study was
      conducted to determine the total number and percentage of humanitarian NGOs that
      are members of HAP. Total expenditures of HAP members in 2010 also was measured
      and compared with the total humanitarian expenditure by all humanitarian NGOs for
      the same year. The reference year of 2010 was chosen in order to be able to
      compile accurate budgets for the largest possible number of HAP members. The
      total number of HAP members for the years 2005 through 2012 was divided by the
      estimated number of humanitarian NGOs active in 2010. The total budgets for HAP
      members in 2010 were divided by the estimated total humanitarian expenditure of
      all NGOs for 2010. RESULTS: As of the beginning of 2012, the percentage of
      humanitarian NGOs that were members of HAP was 1.6% (68 members out of 4400
      organizations). The combined budgets of the member organizations of HAP in 2010
      made up 62.9% of the total humanitarian expenditure for the year 2010 (US $4.65
      billion/7.4 billion). CONCLUSION: A very small proportion of humanitarian NGOs
      have adopted HAP membership. However, HAP members account for almost two-thirds
      of all humanitarian expenditures. The humanitarian sector, therefore, remains
      without a universal regulatory and accountability structure, although progress
      has been made. Efforts should be made to increase the membership within HAP of
      more small to medium sized organizations.

PMID- 25046121
TI  - A semi-homodesmotic approach for estimating ring strain energies (RSEs) of highly
      substituted cyclopropanes that minimizes use of acyclic references and cancels
      steric interactions: RSEs for c-C3R6 that make sense.
AB  - Estimation of ring strain energies (RSEs) of substituted cyclopropanes c
      C(3)H(x)R(6-x) (R = F, Cl, Me; x = 0, 2, 4) using homodesmotic reaction methods
      has been plagued by implausible results. Prior work suggests that this stems from
      poorly canceled interactions between substituents on the acyclic reference
      molecules. We report a semi-homodesmotic approach that minimizes use of acyclic
      references, focusing instead on canceling substituent interactions. The method
      requires employing homodesmotic group equivalent reactions only for disubstituted
      cyclopropanes and relies solely on absolute energy calculations for more
      substituted rings. This provides RSEs consistent with chemical intuition
      regardless of the degree of substitution. We find that RSEs increase with
      substitution regardless of the electronic nature of R, although the increase is
      more dramatic when R is electron-withdrawing. The RSEs determined are consistent
      with QTAIM data, which show that progressive substitution always increases
      critical path angles. Overall, the semi-homodesmotic approach is simpler than
      hyperhomodesmotic reaction methods, and gives more trustworthy results.

PMID- 25046122
TI  - Linguistic inability or poor performance: Dissociating scalar implicature
      generation and mismatch in the developing brain.
AB  - Behavioral investigations of the acquisition of some have shown that children
      favor its logical interpretation (some and possibly all). Adults, however, use
      the pragmatic interpretation (some but not all) derived by a scalar implicature.
      Certain experimental manipulations increase children's rates of adult-like
      responses, indicating that children are capable of computing implicatures. A
      functional MRI (fMRI) study examining adults linked the left inferior frontal
      gyrus (IFG) to implicature computation, and prefrontal regions, the left middle
      frontal gyrus (MFG), and medial frontal gyrus (MeFG), to processing the mismatch
      between implicatures and the context in which they were presented. In the current
      fMRI study, we aimed to determine whether children's failure to give pragmatic
      interpretations to some results from a failure in implicature computation or in
      implicature-mismatch processing. We explored children's brain activations with
      the same experimental task administered to adults. In a region-of-interest
      analysis, children showed an activational pattern similar to the one observed in
      adults in the left IFG with increased activations for the implicature conditions.
      By contrast, in the left MFG, children showed decreased activation for the
      mismatched implicatures compared with matched and no implicature conditions. No
      difference between the conditions was observed in the MeFG. For both implicature
      conditions, no activation in the left IFG was observed when comparing adults and
      children directly. However, for mismatched implicatures, adults showed greater
      activation in the prefrontal regions compared with children. Our results suggest
      that children may have an adult-like computation of implicatures (even when their
      behavior does not necessarily indicate that), but they fail in resolving
      implicature-mismatch situations.

PMID- 25046123
TI  - The prospective contribution of childhood maltreatment to low self-worth, low
      relationship quality, and symptomatology across adolescence: A developmental
      organizational perspective.
AB  - This research investigated the prospective contribution of childhood maltreatment
      to low self-worth, low relationship quality, and symptoms during adolescence.
      Further, the stability and cross-lagged effects of these sequelae of maltreatment
      were examined over time. History of maltreatment during childhood was obtained,
      and youth (407 maltreated, 228 nonmaltreated; 376 males, 259 females) completed 2
      subsequent assessments spaced approximately 2 years apart during early-mid and
      mid-late adolescence. As anticipated, childhood maltreatment experiences
      predicted low self-worth, low relationship quality, and both internalizing and
      externalizing symptoms in early-mid adolescence. Beyond the stability paths of
      each outcome variable, significant cross-lagged effects were observed among low
      self-worth, low relationship quality, and internalizing symptoms across
      adolescence. In contrast, cross-lagged effects were not observed among adolescent
      externalizing symptoms. These findings support a developmental-organizational
      model in which childhood maltreatment creates multiple vulnerabilities that
      evince continuity and generate mutually influencing effects across adolescence.

PMID- 25046124
TI  - Reciprocal relations between perceived parental knowledge and adolescent
      substance use and delinquency: The moderating role of parent-teen relationship
      quality.
AB  - The current study prospectively examined hypothesized short- and long-term
      reciprocal relations between perceived parental knowledge and adolescent heavy
      episodic drinking, marijuana use, and delinquency. Using the contextual model of
      parenting style (Darling & Steinberg, 1993), we examined the extent to which the
      bidirectional nature of associations between knowledge and adolescent outcomes is
      dependent on a facet of parenting style: the quality of the parent-child
      relationship. Data came from the first 4 waves of the National Longitudinal Study
      of Youth 1997. The sample for the current study consisted of 5,419 students
      between 12 and 14 years of age at baseline (52% male) surveyed annually for 4
      years. Parallel process, autoregressive latent trajectory models were used to
      examine relations between initial levels and change over time in perceived
      parental knowledge and adolescent risk, and short-term cross-lagged paths were
      included to examine bidirectionality while accounting for long-term associations.
      Results showed significant short-term and long-term bidirectionality between
      perceived parental knowledge and adolescent outcomes, with parent effects on
      students and student effects on parents. Long-term associations across constructs
      were negative, whereas short-term associations were positive. These reciprocal
      associations were shown to differ across levels of parent-child relationship
      quality with regard to adolescent heavy episodic drinking and delinquency,
      providing support for the contextual model of parenting style. Implications for
      future work on parent-child bidirectional relationships and parent-based
      interventions are discussed.

PMID- 25046125
TI  - Moderating effects of group status, cohesion, and ethnic composition on
      socialization of aggression in children's peer groups.
AB  - We explored the effects of 3 group features (i.e., status, cohesion, and ethnic
      composition) on socialization processes of aggression in early adolescents'
      natural peer social groups. Gender differences in these effects were also
      determined. A total of 245 seventh-grade individuals belonging to 65 peer groups
      were included in the analyses. All 3 group features moderated the strength of
      group socialization on physical aggression with the exception of group status on
      girls' physical aggression. Stronger socialization of physical aggression
      occurred in higher status, more cohesive, or ethnically more homogeneous groups.
      In contrast, only group cohesion moderated the strength of group socialization on
      social aggression among girls. These findings suggest that somewhat different
      processes may be involved in peer group influences on different forms of
      aggression. Future intervention and prevention efforts for adolescent aggression
      should consider peer group membership and group features simultaneously.

PMID- 25046126
TI  - Growth trajectories of early aggression, overactivity, and inattention: Relations
      to second-grade reading.
AB  - The link between behavior problems and low academic achievement is well
      established, but few studies have examined longitudinal relations between early
      externalizing behaviors before school entry and low academic achievement
      following transition to formal schooling. Early inattention has been particularly
      overlooked, despite strong associations between inattention and reading
      difficulties later in development. Trajectories of infant and toddler aggression,
      overactivity, and inattention, developed from parent reports about 1- to 3-year
      old children, were examined as predictors of direct assessments of 2nd-grade
      reading in an at-risk epidemiological study subsample (N = 359). Reports of
      inattentive and overactive behaviors at ages 1-3 years and changes in inattention
      through toddlerhood predicted reading achievement in 2nd grade. A parallel
      process model suggested that the effects of early inattention on reading appear
      to be most robust. Findings underscore the contribution of social-emotional
      development to school readiness and the importance of early identification of
      children with externalizing problems, as early interventions designed to reduce
      externalizing problems may improve later reading skills.

PMID- 25046127
TI  - Immobilizing gold nanoparticles in mesoporous silica covered reduced graphene
      oxide: a hybrid material for cancer cell detection through hydrogen peroxide
      sensing.
AB  - A new kind of two-dimensional (2-D) hybrid material (RGO-PMS@AuNPs), fabricated
      by the immobilization of ultrasmall gold nanoparticles (AuNPs, ~3 nm) onto
      sandwich-like periodic mesopourous silica (PMS) coated reduced graphene oxide
      (RGO), was employed for both electrocatalytic application and cancer cell
      detection. The hybrid-based electrode sensor showed attractive electrochemical
      performance for sensitive and selective nonenzymatic detection of hydrogen
      peroxide (H2O2) in 0.1 M phosphate buffered saline, with wide linear detection
      range (0.5 MUM to 50 mM), low detection limit (60 nM), and good sensitivity (39.2
      MUA mM(-1) cm(-2)), and without any interference by common interfering agents. In
      addition, the sensor exhibited a high capability for glucose sensing and H2O2
      detection in human urine. More interestingly, the hybrid was found to be
      nontoxic, and the electrode sensor could sensitively detect a trace amount of
      H2O2 in a nanomolar level released from living tumor cells (HeLa and HepG2).
      Because the hybrid presents significant properties for the detection of bioactive
      species and certain cancerous cells by the synergistic effect from RGO, PMS, and
      AuNPs, it could be able to serve as a versatile platform for biosensing,
      bioanalysis, and biomedical applications. 

PMID- 25046129
TI  - Hydrogen bonds and steric effects induced structural modulation of three layered
      iodoplumbate hybrids from nonperovskite to perovskite structure.
AB  - Directed by diprotonated organic diamines containing both primary and tertiary
      ammonium groups, three layered iodoplumbate hybrids, {[H2DMPDA][PbI4]}n (1),
      {[H2DEPDA]4[Pb5I18]}n (2) and {[H2TMEDA][Pb3I8]}n (3) (DMPDA = N,N-dimethyl-1,3
      propanediamine, DEPDA = N,N-diethyl-1,3-propanediamine, TMEDA = N,N,N',N'
      tetramethylethylenediamine), have been synthesized solvothermally. 1 presents a
      layered perovskite structure based on corner-sharing PbI6 octahedra, compound 2
      consists of a Pb4I20 perovskite motif and a Pb2I10 dimeric motif and compound 3
      comprises Pb3I13 units connected by face-sharing and edge-sharing modes.
      Structural modulations from nonperovskite to perovskite structure are strongly
      correlated to steric effects and hydrogen bonding interaction at the organic
      inorganic interface. Band gaps for 1-3 , estimated as 2.21, 2.58 and 2.73 eV,
      respectively, also reveal an interesting correlation with structural modulation,
      and the red shift for 1 is attributed to large Pb-I(equatorial)-Pb bond angles.

PMID- 25046128
TI  - Structure and Stereochemical Determination of Hypogeamicins from a Cave-Derived
      Actinomycete.
AB  - Culture extracts from the cave-derived actinomycete Nonomuraea specus were
      investigated, resulting in the discovery of a new S-bridged pyronaphthoquinone
      dimer and its monomeric progenitors designated hypogeamicins A-D (1-4). The
      structures were elucidated using NMR spectroscopy, and the relative
      stereochemistries of the pyrans were inferred using NOE and comparison to
      previously reported compounds. Absolute stereochemistry was determined using
      quantum chemical calculations of specific rotation and vibrational and electronic
      circular dichroism spectra, after an extensive conformational search and
      including solute-solvent polarization effects, and comparing with the
      corresponding experimental data for the monomeric congeners. Interestingly, the
      dimeric hypogeamicin A (1) was found to be cytotoxic to the colon cancer derived
      cell line TCT-1 at low micromolar ranges, but not bacteria, whereas the monomeric
      precursors possessed antibiotic activity but no significant TCT-1 cytotoxicity. 

PMID- 25046130
TI  - Molecular iron(III) phosphonates: synthesis, structure, magnetism, and Mossbauer
      studies.
AB  - The reaction of Fe(ClO4)2.6H2O with t-BuPO3H2 or Cl3CPO3H2 in the presence of an
      ancillary pyrazole phenolate as a coligand, H2phpzH [H2phpzH = 3(5)-(2
      hydroxyphenyl)pyrazole], afforded tetra- and pentanuclear Fe(III) phosphonate
      complexes [Fe4(t-BuPO3)4(HphpzH)4].5CH3CN.5CH2Cl2 (1) and [HNEt3]2[Fe5(MU3-O)(MU
      OH)2 (Cl3CPO3)3(HphpzH)5(MU-phpzH].3CH3CN.2H2O (2). Single-crystal X-ray
      structural analysis reveals that 1 possesses a cubic double-4-ring (D4R) core
      similar to what is found in zeolites. The molecular structure of 2 reveals it to
      be pentanuclear. It crystallizes in the chiral P1 space group. Magnetic studies
      on 1 and 2 have also been carried out, which reveal that the bridging phosphonate
      ligands mediate weak antiferromagnetic interactions between the Fe(III) ions.
      Magnetization dynamics of 1 and 2 have been corroborated by a Mossbauer
      spectroscopy analysis. 

PMID- 25046132
TI  - Oxygen vacancy effects on an amorphous-TaOx-based resistance switch: a first
      principles study.
AB  - Amorphous TaOx (a-TaOx) based resistance switches have recently demonstrated
      outstanding performance and are being considered as one of the most promising
      candidates for next-generation memory cells. However, the origin of the switching
      mechanism is still under debate, especially on the component of the conduction
      filament (CF). Since the resistance change of a-TaOx is controlled by the O
      concentration, we perform a systematic investigation on the evolution of
      structures and electronic properties of a-TaOx (0.75 <= x <= 2.85) from first
      principles. Our results reveal the strong correlation among Ta/O coordination
      numbers, Ta-Ta/Ta-O bond lengths, and O concentrations in a-TaOx. For a single O
      vacancy in a-TaO2.5, the Ta-Ta dimer structure is found to be the most stable,
      and the energy position of its defect state agrees well with experiments. With
      the decrease of O concentration, Ta atoms tend to merge together and finally form
      a continuous Ta-rich region in a-TaO0.75, which suggests that not O vacancies,
      but the Ta-Ta bonding mainly contributes to the CF in a-TaOx based resistance
      switches. Our molecular dynamics simulation suggests that in the CF, Ta atoms
      prefer to arrange in a layer structure, and hence the phase transformation to
      crystalline alpha-Ta with interstitial O atoms is proposed. In addition, the
      calculations on Pt/a-TaOx/Pt heterostructures further confirm the conductive
      nature of the Ta-Ta bonding in a-TaOx, and also reveal the different conduction
      types in switching on (metallic contact) and off (electron hopping) states. 

PMID- 25046131
TI  - The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
      Statement: guidelines for reporting observational studies.
AB  - Much biomedical research is observational. The reporting of such research is
      often inadequate, which hampers the assessment of its strengths and weaknesses
      and of a study's generalisability. The Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) Initiative developed
      recommendations on what should be included in an accurate and complete report of
      an observational study. We defined the scope of the recommendations to cover
      three main study designs: cohort, case-control, and cross-sectional studies. We
      convened a 2-day workshop in September 2004, with methodologists, researchers,
      and journal editors to draft a checklist of items. This list was subsequently
      revised during several meetings of the coordinating group and in e-mail
      discussions with the larger group of STROBE contributors, taking into account
      empirical evidence and methodological considerations. The workshop and the
      subsequent iterative process of consultation and revision resulted in a checklist
      of 22 items (the STROBE Statement) that relate to the title, abstract,
      introduction, methods, results, and discussion sections of articles. 18 items are
      common to all three study designs and four are specific for cohort, case-control,
      or cross-sectional studies. A detailed Explanation and Elaboration document is
      published separately and is freely available on the Web sites of PLoS Medicine,
      Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement
      will contribute to improving the quality of reporting of observational studies. 

PMID- 25046133
TI  - Discriminating speech rhythms in audition, vision, and touch.
AB  - We investigated the extent to which people can discriminate between languages on
      the basis of their characteristic temporal, rhythmic information, and the extent
      to which this ability generalizes across sensory modalities. We used rhythmical
      patterns derived from the alternation of vowels and consonants in English and
      Japanese, presented in audition, vision, both audition and vision at the same
      time, or touch. Experiment 1 confirmed that discrimination is possible on the
      basis of auditory rhythmic patterns, and extended it to the case of vision, using
      'aperture-close' mouth movements of a schematic face. In Experiment 2, language
      discrimination was demonstrated using visual and auditory materials that did not
      resemble spoken articulation. In a combined analysis including data from
      Experiments 1 and 2, a beneficial effect was also found when the auditory
      rhythmic information was available to participants. Despite the fact that
      discrimination could be achieved using vision alone, auditory performance was
      nevertheless better. In a final experiment, we demonstrate that the rhythm of
      speech can also be discriminated successfully by means of vibrotactile patterns
      delivered to the fingertip. The results of the present study therefore
      demonstrate that discrimination between language's syllabic rhythmic patterns is
      possible on the basis of visual and tactile displays. 

PMID- 25046134
TI  - Susceptibility mapping of air, bone, and calcium in the head.
AB  - PURPOSE: To demonstrate the mapping of structures with high susceptibility
      values, such as the sinuses, bones and teeth, using short echo times. METHODS:
      Four in vivo datasets were collected with a gradient-echo sequence (TE1 = 2.5 ms,
      TE2 = 5 ms and TE3 = 7.5 ms). Complex division was performed to remove the phase
      offset term and generate the phase at TE = 2.5 ms. Susceptibility maps were
      generated from unwrapped phase images, using a geometry-constrained iterative
      algorithm, by preserving phase information in the extracerebral tissues. The
      susceptibility results were improved by updating the missing phase information
      inside structures with no signal using the predicted phase at each iteration
      step. Simulated phase images of a three-dimensional brain model and tooth phantom
      were used to validate the proposed method. RESULTS: Improved susceptibility maps
      were obtained once the phase information in the extracerebral tissue region was
      incorporated, for both the model and in vivo data. For in vivo data, the average
      susceptibilities of air (sphenoid sinus), bone and calcium (teeth) were found to
      be (in ppm): Deltachi(sinus-tissue)  = +9.2 +/- 1.3, Deltachi(bone-tissue)  = 
      2.1 +/- 0.6 and Deltachi(teeth-tissue)  = -3.3 +/- 1.2, respectively. CONCLUSION:
      High susceptibility structures with little or no signal can be imaged using
      quantitative susceptibility mapping and can be used to improve background field
      removal.

PMID- 25046135
TI  - Topological surface state enhanced photothermoelectric effect in Bi2Se3
      nanoribbons.
AB  - The photothermoelectric effect in topological insulator Bi2Se3 nanoribbons is
      studied. The topological surface states are excited to be spin-polarized by
      circularly polarized light. Because the direction of the electron spin is locked
      to its momentum for the spin-helical surface states, the photothermoelectric
      effect is significantly enhanced as the oriented motions of the polarized spins
      are accelerated by the temperature gradient. The results are explained based on
      the microscopic mechanisms of a photon induced spin transition from the surface
      Dirac cone to the bulk conduction band. The as-reported enhanced
      photothermoelectric effect is expected to have potential applications in a spin
      polarized power source. 

PMID- 25046136
TI  - Simple and robust saturation-based slice selection for ultrashort echo time MRI.
AB  - PURPOSE: To present a new method for localizing signal within a two-dimensional
      (2D) slice suitable for ultrashort echo time (UTE) imaging, called saturation
      based UTE (sat-UTE). The new method digitally subtracts two acquisitions that are
      nonselectively excited with and without selective saturation of the slice of
      interest. METHODS: Sat-UTE was compared with half-pulse and double-half pulse
      excited UTE within phantoms, as well as 3D-UTE within ex vivo femur and in vivo
      tibia. Numerical simulations were also used to quantify the effects of slice
      profile broadening and signal component amplitudes for quantitative UTE. RESULTS:
      Sat-UTE is robust to suppress out-of-slice signal, and produces short T2 signal
      decay curves comparable to 3D-UTE, but has a lower signal to noise ratio
      efficiency compared with other slice-selective methods. CONCLUSION: The proposed
      method is useful for fast, quantitative evaluation of short T2 signals, and is
      insensitive to gradient performance.

PMID- 25046137
TI  - Prevention of DNA damage by L-carnitine induced by metabolites accumulated in
      maple syrup urine disease in human peripheral leukocytes in vitro.
AB  - Maple syrup urine disease (MSUD) is an inherited aminoacidopathy caused by a
      deficiency in branched-chain alpha-keto acid dehydrogenase complex activity that
      leads to the accumulation of the branched-chain amino acids (BCAAs) leucine
      (Leu), isoleucine, and valine and their respective alpha-keto-acids, alpha
      ketoisocaproic acid (KIC), alpha keto-beta-methylvaleric acid, and alpha
      ketoisovaleric acid. The major clinical features presented by MSUD patients
      include ketoacidosis, failure to thrive, poor feeding, apnea, ataxia, seizures,
      coma, psychomotor delay, and mental retardation; however, the pathophysiology of
      this disease is poorly understood. MSUD treatment consists of a low protein diet
      supplemented with a mixture containing micronutrients and essential amino acids
      but excluding BCAAs. Studies have shown that oxidative stress may be involved in
      the neuropathology of MSUD, with the existence of lipid and protein oxidative
      damage in affected patients. In recent years, studies have demonstrated the
      antioxidant role of L-carnitine (L-Car), which plays a central function in
      cellular energy metabolism and for which MSUD patients have a deficiency. In this
      work, we investigated the in vitro effect of Leu and KIC in the presence or
      absence of L-Car on DNA damage in peripheral whole blood leukocytes using the
      alkaline comet assay with silver staining and visual scoring. Leu and KIC
      resulted in a DNA damage index that was significantly higher than that of the
      control group, and L-Car was able to significantly prevent this damage, mainly
      that due to KIC.

PMID- 25046138
TI  - Analysis of midgut gene expression profiles from different silkworm varieties
      after exposure to high temperature.
AB  - The silkworm is a poikilothermic animal, whose growth and development is
      significantly influenced by environmental temperature. To identify genes and
      metabolic pathways involved in the heat-stress response, digital gene expression
      analysis was performed on the midgut of the thermotolerant silkworm variety '932'
      and thermosensitive variety 'HY' after exposure to high temperature (932T and
      HYT). Deep sequencing yielded 6,211,484, 5,898,028, 5,870,395 and 6,088,303 reads
      for the 932, 932T, HY and HYT samples, respectively. The annotated genes
      associated with these tags numbered 4357, 4378, 4296 and 4658 for the 932, 932T,
      HY and HYT samples, respectively. In the HY-vs-932, 932-vs-932T, and HY-vs-HYT
      comparisons, 561, 316 and 281 differentially expressed genes were identified,
      which could be assigned to 179, 140 and 123 biological pathways, respectively. It
      was found that some of the biological pathways, which included oxidative
      phosphorylation, related to glucose and lipid metabolism, are greatly affected by
      high temperature and may lead to a decrease in the ingestion of fresh mulberry.
      When subjected to an early period of continuous heat stress, HSP genes, such as
      HSP19.9, HSP23.7, HSP40-3, HSP70, HSP90 and HSP70 binding protein, are up
      regulated but then reduced after 24h and the thermotolerant '932' strain has
      higher levels of mRNA of some HSPs, except HSP70, than the thermosensitive
      variety during continuous high temperature treatment. It is suggested that HSPs
      and the levels of their expression may play important roles in the resistance to
      high temperature stress among silkworm varieties. This study has generated
      important reference tools that can be used to further analyze the mechanisms that
      underlie thermotolerance differences among silkworm varieties.

PMID- 25046139
TI  - Heterologous expression of betaine aldehyde dehydrogenase gene from
      Ammopiptanthus nanus confers high salt and heat tolerance to Escherichia coli.
AB  - Betaine aldehyde dehydrogenase (BADH) catalyzes the synthesis of glycine betaine,
      a regulator of osmosis, and therefore BADH is considered to play a significant
      role in response of plants to abiotic stresses. Here, based on the conserved
      residues of the deduced amino acid sequences of the homologous BADH genes, we
      cloned the AnBADH gene from the xerophytic leguminous plant Ammopiptanthus nanus
      by using reverse transcription PCR and rapid amplification of cDNA ends. The full
      length cDNA is 1,868 bp long without intron, and contains an open reading frame
      of 1512 bp, and 3'- and 5'-untranslated regions of 294 and 62 bp. It encodes a
      54.71 kDa protein of 503 amino acids. The deduced amino acid sequence shares high
      homology, conserved amino acid residues and sequence motifs crucial for the
      function with the BADHs in other leguminous species. The sequence of the open
      reading frame was used to construct a prokaryotic expression vector pET32a
      AnBADH, and transform Escherichia coli. The transformants expressed the
      heterologous AnBADH gene under the induction of isopropyl beta-D
      thiogalactopyranoside, and demonstrated significant enhancement of salt and heat
      tolerance under the stress conditions of 700 mmol L(-1) NaCl and 55 degrees C
      high temperature. This result suggests that the AnBADH gene might play a crucial
      role in adaption of A. nanus to the abiotic stresses, and have the potential to
      be applied to transgenic operations of commercially important crops for
      improvement of abiotic tolerance.

PMID- 25046140
TI  - Excisions of a defective transposable CACTA element (Tetu1) generate new alleles
      of a CYCLOIDEA-like gene of Helianthus annuus.
AB  - Tubular ray flower (turf) is a sunflower mutant that caught attention because it
      bears actinomorphic ray flowers, due to the presence of an active, although non
      autonomous CACTA transposon (Tetu1) in the TCP domain of a CYCLOIDEA-like gene,
      HaCYC2c, a major regulator of sunflower floral symmetry. Here, we analyzed its
      excision rates in F3 population deriving from independent crosses of turf with
      common sunflower accessions. Our results suggest that the excision rate, ranging
      from 1.21 to 6.29%, depends on genetic background; moreover, the absence of
      somatic sectors in inflorescences of revertant individuals analyzed (182) and
      genetic analyses suggests a tight developmental control of Tetu1 excision, likely
      restricted to germinal cells. We individuate events of Tetu1 excision through
      molecular analysis that restore the wild type (WT) HaCYC2c allele, but even
      transposon excisions during which footprints are left. All mutations we detected
      occurred at the TCP basic motif and cause a change in ray flower phenotype. In
      particular, we selected five mutants with a one-to-four amino acid change that
      influence the capacity of reproductive organ development and ray flower corolla
      shaping (MUT-1, -2, -3, -4, -5). Revertant alleles not affecting turf phenotype
      (i.e. reading frame mutations) have also been identified (MUT-6). In all mutants,
      Real-time quantitative PCR (qPCR) experiments revealed variations of the steady
      state level of HaCYC2c mRNA. MUT-1 and MUT-4 showed a significant HaCYC2c down
      regulation with respect to WT. A large variation within the biological replicates
      of MUT-2, MUT-3 and MUT-5 was detected and not significant differences in
      transcription levels between mutants and WT were observed. We detected low steady
      state level of HaCYC2c mRNA both in turf as in MUT-6. A three dimensional (3D)
      structure prediction tool let us predict an incorrect folding of the TCP protein
      already after a single amino acid deletion. This in turn is detectable as the
      restore of traits that are not peculiar of WT ray flowers, such as male
      fertility. Our analysis of an active TE sheds light on the TCP motif of the
      HaCYC2c gene and suggests that Tetu1 may be useful to obtain new natural mutants
      and for transposon tagging in different inbred lines of sunflower.

PMID- 25046141
TI  - The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of
      melanoma brain metastasis.
AB  - Brain metastases occur frequently in melanoma patients with advanced disease
      whereby the prognosis is dismal. The underlying mechanisms of melanoma brain
      metastasis development are not well understood. Identification of molecular
      determinants regulating melanoma brain metastasis would advance the development
      of prevention and therapy strategies for this disease. Gene expression profiles
      of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor
      models established in our laboratory revealed that expression of tight junction
      component CLDN1 was lower in the brain-metastasizing variants than in cutaneous
      variants from the same melanoma. The objective of our study was to determine the
      significance of CLDN1 downregulation/loss in metastatic melanoma and its role in
      melanoma brain metastasis. An immunohistochemical analysis of human cells of the
      melanocyte lineage indicated a significant CLDN1 downregulation in metastatic
      melanomas. Transduction of melanoma brain metastatic cells expressing low levels
      of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1
      overexpressing melanoma cells expressed a lower ability to migrate and adhere to
      extracellular matrix, reduced tumor aggressiveness in nude mice and, most
      importantly, eliminated the formation of micrometastases in the brain. In sharp
      contrast, the ability of the CLDN1-overexpressing cells to form lung
      micrometastases was not impaired. CLDN1-mediated interactions between these cells
      and brain endothelial cells constitute the mechanism underlying these results.
      Taken together, we demonstrated that downregulation or loss of CLDN1 supports the
      formation of melanoma brain metastasis, and that CLDN1 expression could be a
      useful prognostic predictor for melanoma patients with a high risk of brain
      metastasis. 

PMID- 25046142
TI  - Modulation of the mitochondrial large-conductance calcium-regulated potassium
      channel by polyunsaturated fatty acids.
AB  - Polyunsaturated fatty acids (PUFAs) and their metabolites can modulate several
      biochemical processes in the cell and thus prevent various diseases. PUFAs have a
      number of cellular targets, including membrane proteins. They can interact with
      plasma membrane and intracellular potassium channels. The goal of this work was
      to verify the interaction between PUFAs and the most common and intensively
      studied mitochondrial large conductance Ca(2+)-regulated potassium channel
      (mitoBKCa). For this purpose human astrocytoma U87 MG cell lines were
      investigated using a patch-clamp technique. We analyzed the effects of
      arachidonic acid (AA); eicosatetraynoic acid (ETYA), which is a non-metabolizable
      analog of AA; docosahexaenoic acid (DHA); and eicosapentaenoic acid (EPA). The
      open probability (Po) of the channel did not change significantly after
      application of 10MUM ETYA. Po increased, however, after adding 10MUM AA. The
      application of 30MUM DHA or 10MUM EPA also increased the Po of the channel.
      Additionally, the number of open channels in the patch increased in the presence
      of 30MUM EPA. Collectively, our results indicate that PUFAs regulate the BKCa
      channel from the inner mitochondrial membrane. 

PMID- 25046143
TI  - Maximizing photosynthetic efficiency and culture productivity in cyanobacteria
      upon minimizing the phycobilisome light-harvesting antenna size.
AB  - A phycocyanin-deletion mutant of Synechocystis (cyanobacteria) was generated upon
      replacement of the CPC-operon with a kanamycin resistance cassette. The Deltacpc
      transformant strains (Deltacpc) exhibited a green phenotype, compared to the blue
      green of the wild type (WT), lacked the distinct phycocyanin absorbance at 625nm,
      and had a lower Chl per cell content and a lower PSI/PSII reaction center ratio
      compared to the WT. Molecular and genetic analyses showed replacement of all WT
      copies of the Synechocystis DNA with the transgenic version, thereby achieving
      genomic DNA homoplasmy. Biochemical analyses showed the absence of the
      phycocyanin alpha- and beta-subunits, and the overexpression of the kanamycin
      resistance NPTI protein in the Deltacpc. Physiological analyses revealed a
      higher, by a factor of about 2, intensity for the saturation of photosynthesis in
      the Deltacpc compared to the WT. Under limiting intensities of illumination,
      growth of the Deltacpc was slower than that of the WT. This difference in the
      rate of cell duplication diminished gradually as growth irradiance increased.
      Identical rates of cell duplication of about 13h for both WT and Deltacpc were
      observed at about 800MUmolphotonsm(-2)s(-1) or greater. Culture productivity
      analyses under simulated bright sunlight and high cell-density conditions showed
      that biomass accumulation by the Deltacpc was 1.57-times greater than that
      achieved by the WT. Thus, the work provides first-time direct evidence of the
      applicability of the Truncated Light-harvesting Antenna (TLA)-concept in
      cyanobacteria, entailing substantial improvements in the photosynthetic
      efficiency and productivity of mass cultures upon minimizing the phycobilisome
      light-harvesting antenna size. 

PMID- 25046144
TI  - Biographical sketch: Jason Brice.
AB  - This article is a biographical sketch of retired British neurosurgeon Jason
      Brice, who is a pioneer of deep brain stimulation and helped establish the Wessex
      Neurological Centre.

PMID- 25046145
TI  - Trans-foramen ovale biopsy of a parasellar lesion guided by intraoperative CT
      neuronavigation with MRI fusion: a case report.
AB  - A 23-year-old male presented with a parasellar lesion which was suspected as
      disseminated intracranial germ cell tumour. The diagnosis of germinoma was made
      using immunohistochemistry from percutaneous trans-foramen ovale biopsy. This
      report describes the role of neuronavigation-guided biopsy through the foramen
      ovale for lesions in the parasellar region.

PMID- 25046146
TI  - Phonatory effects of type I thyroplasty implant shape and depth of medialization
      in unilateral vocal fold paralysis.
AB  - OBJECTIVES/HYPOTHESIS: Medialization thyroplasty (MT) is commonly used to treat
      glottic insufficiency. In this study, we investigated the phonatory effects of MT
      implant medialization depth and medial surface shape. METHODS: Recurrent
      laryngeal nerve (RLN) and vagal paralysis were simulated in an in vivo canine. A
      type 1 MT was performed using a silicone elastomer implant with variable
      medialization depths and medial surface shapes: rectangular, V-shaped, divergent,
      and convergent. The effects on phonation onset flow/pressure relationships and
      acoustics were measured. RESULTS: Increasing depth of medialization led to
      improvements in fundamental frequency (F0) range and normalization of the slope
      of pressure/flow relationship toward baseline activation conditions. The effects
      of implant medial shape also depended on depth of medialization. Outcome measures
      were similar among the implants at smaller medialization depths. With large
      medialization depths and vagal paralysis conditions, the divergent implant
      maintained pressure/flow relationship closer to baseline. The vagal paralysis
      conditions also demonstrated decreased fundamental frequency range and worse
      flow/pressure relationship compared to RLN paralysis. CONCLUSIONS: The depth and
      medial shape of a medialization laryngoplasty (ML) implant significantly affect
      both the F0 range and aerodynamic power required for phonation. These effects
      become more notable with increasing depth of medialization. The study also
      illustrates that ML is less effective in vagal paralysis compared to RLN
      paralysis. LEVEL OF EVIDENCE: N/A.

PMID- 25046148
TI  - Mesityllithium and p-(dimethylamino)phenyllithium for the selective alternate
      trilithiation of the hexaphenylbenzene framework.
AB  - We report mesityllithium and p-(dimethylamino)phenyllithium as new valuable
      lithiating reagents, which realize Br/Li exchange reaction of bromoarenes at
      relatively high temperature in THF. With these reagents, we established the
      general and practical protocols for the selective alternate trilithiation of the
      hexaphenylbenzene framework. 

PMID- 25046147
TI  - Pancreatic transduction by helper-dependent adenoviral vectors via intraductal
      delivery.
AB  - Pancreatic gene transfer could be useful to treat several diseases, such as
      diabetes mellitus, cystic fibrosis, chronic pancreatitis, or pancreatic cancer.
      Helper-dependent adenoviral vectors (HDAds) are promising tools for gene therapy
      because of their large cloning capacity, high levels of transgene expression, and
      long-term persistence in immunocompetent animals. Nevertheless, the ability of
      HDAds to transduce the pancreas in vivo has not been investigated yet. Here, we
      have generated HDAds carrying pancreas-specific expression cassettes, that is,
      driven either by the elastase or insulin promoter, using a novel and convenient
      plasmid family and homologous recombination in bacteria. These HDAds were
      delivered to the pancreas of immunocompetent mice via intrapancreatic duct
      injection. HDAds, encoding a CMV-GFP reporter cassette, were able to transduce
      acinar and islet cells, but transgene expression was lost 15 days postinjection
      in correlation with severe lymphocytic infiltration. When HDAds encoding GFP
      under the control of the specific elastase promoter were used, expression was
      detected in acinar cells, but similarly, the expression almost disappeared 30
      days postinjection and lymphocytic infiltration was also observed. In contrast,
      long-term transgene expression (>8 months) was achieved with HDAds carrying the
      insulin promoter and the secretable alkaline phosphatase as the reporter gene.
      Notably, transduction of the liver, the preferred target for adenovirus, was
      minimal by this route of delivery. These data indicate that HDAds could be used
      for pancreatic gene therapy but that selection of the expression cassette is of
      critical importance to achieve long-term expression of the transgene in this
      tissue.

PMID- 25046149
TI  - Apparent CD19 expression by natural killer cells: A potential confounder for
      minimal residual disease detection by flow cytometry in B lymphoblastic leukemia.
AB  - Detection of minimal residual disease (MRD) by flow cytometry (FCM) in B
      lymphoblastic leukemia (B ALL) is important for guiding patient specific clinical
      management. We describe apparent expression of CD19 by natural killer (NK) cells
      as a potential confounder in the detection of B ALL MRD by FCM. This finding was
      noted in seven different patient samples analyzed on different days as part of
      routine clinical care in our laboratory, with analysis of different anti-CD19
      antibody clones and fluorochrome conjugates in five of the seven samples.
      Although the etiology of this finding is not clear, possibilities include true
      low level expression and trogocytosis. We highlight this finding to avoid
      potential misinterpretation when evaluating samples for MRD in patients with B
      lineage neoplasms, particularly in B ALL. (c) 2014 Clinical Cytometry Society.

PMID- 25046150
TI  - Antithrombotics in atrial fibrillation and coronary disease.
AB  - Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and
      approximately 18-45% of AF patients have concomitant coronary artery disease
      (CAD). Several studies have demonstrated that oral anticoagulation is the
      mainstay of therapy for stroke prevention in AF. Similarly, antiplatelet therapy
      including aspirin and P2Y12 inhibitor is recommended in the management of acute
      coronary syndrome and stable CAD. Despite the high prevalence of CAD with AF,
      practice guidelines are scarce on the appropriate antithrombotic regimen due to
      lack of large-scale randomized clinical trials. The use of direct thrombin and
      factor Xa inhibitors for stroke prevention in AF has also complicated the
      possible combinations of antithrombotic therapies. This review aims to discuss
      the available evidence regarding aspirin as an antithrombotic strategy, the role
      of novel anticoagulants and the specific clinical situations where aspirin may be
      beneficial in patients with AF and CAD. 

PMID- 25046151
TI  - Treating breast cancer radiotherapy-induced moist desquamation with a traditional
      Chinese medicine formula: a case series pilot study.
AB  - Abstract Objective: A case series is presented to investigate the efficacy and
      safety of Erhegao for patients with breast cancer who have radiotherapy-induced
      moist desquamation. METHODS: Eighteen women with breast cancer who received
      radiotherapy and developed moist desquamation were enrolled. Erhegao cream, a
      Traditional Chinese Medicine formula consisting of zinc oxide powder, calamine
      powder, and lithospermum oil, was applied on areas of moist desquamation.
      Application was repeated once a day until healing. The primary end point for
      efficacy was the time to healing of the moist desquamation areas. A numerical
      rating scale was used to measure wound pain relief daily. Incidence of toxicity
      was also assessed. RESULTS: The average time to healing of the moist desquamation
      area was 13.56 days. The mean pain scores on the first, third, and seventh days
      were 5.22, 2.94, and 0.83, respectively. Eight-three percent of patients reported
      pain relief after the first 3 days, and 94%, after the first week. The mean daily
      reduction in the pain score was 0.40. None of the patients developed clinical
      infections or reported any toxicity. CONCLUSIONS: This formula is effective and
      safe, especially for pain relief, and may be an alternative treatment for
      radiotherapy-induced moist desquamation in patients with breast cancer. Future
      randomized, controlled studies are needed to better evaluate the efficacy of
      Erhegao cream.

PMID- 25046152
TI  - Hibernation induces immune changes in the lung of 13-lined ground squirrels
      (Ictidomys tridecemlineatus).
AB  - During hibernation, significant changes occur in the systemic and intestinal
      immune populations. We found that the lungs of hibernating 13-lined ground
      squirrels (Ictidomys tridecemlineatus) also undergo shifts in immune phenotype.
      Within the population of mononuclear cells, the percentage of T cells increases
      and the percentage of CD11b/c(+) cells decreases in hibernators. E-selectin,
      which promotes endothelial attachment, increases during arousal from torpor.
      Levels of the anti-inflammatory cytokine interleukin (IL)-10 in the lung are
      lower during hibernation while levels of the pro-inflammatory cytokine, tumor
      necrosis factor (TNF)-alpha remain constant. Expression of suppressor of cytokine
      signaling (SOCS) proteins is also decreased in torpid hibernators. Our data point
      to a unique immune phenotype in the lung of hibernating ground squirrels in which
      certain immunosuppressive proteins are downregulated while some potentially
      inflammatory proteins are maintained or amplified. This indicates that the lung
      houses an immune population that can potentially respond to antigenic challenge
      during hibernation.

PMID- 25046153
TI  - Enhanced osteogenic differentiation of mesenchymal stem cells on poly(L-lactide)
      nanofibrous scaffolds containing carbon nanomaterials.
AB  - Carbon nanomaterials (CNMs), such as carbon nanotube (CNT) and graphene, are
      highlighted in bone regeneration because of their osteoinductive properties.
      Their combinations with nanofibrous polymeric scaffolds, which mimic the
      morphology of natural extracellular matrix of bone, arouse keen interest in bone
      tissue engineering. To this end, CNM were incorporated into nanofibrous poly(L
      lactic acid) scaffolds by thermal-induced phase separation. The CNM-containing
      composite nanofibrous scaffolds were biologically evaluated by both in vitro co
      culture of bone mesenchymal stem cells (BMSCs) and in vivo implantation. The
      nanofibrous structure itself demonstrated significant enhancement in cell
      adhesion, proliferation and oseogenic differentiation of BMSCs, and with the
      incorporation of CNM, the composite nanofibrous scaffolds further promoted
      osteogenic differentiation of BMSCs significantly. Between the two CNMs, graphene
      showed stronger effect in promoting osteogenic differentiation of BMSCs than CNT.
      The results of in vivo experiments revealed that the composite nanofibrous
      scaffolds had both good biocompatibility and strong ability in inducing
      osteogenesis. CNMs could remarkably enhance the expression of osteogenesis
      related proteins as well as the formation of type I collagen. Similarly, the
      graphene-containing composite nanofibrous scaffolds demonstrated the strongest
      effect on inducing osteogenesis in vivo. These findings demonstrated that CNM
      containing composite nanofibrous scaffolds were obviously more efficient in
      promoting osteogenesis than pure polymeric scaffolds.

PMID- 25046155
TI  - "The same thing in a different box": similarity and difference in pharmaceutical
      sex hormone consumption and marketing.
AB  - The contraceptive pill has given way to a multitude of products, kinds of
      packaging, and modes of administration. This article draws on work on the
      pharmaceutical copy, extending the analysis to differentiating between forms of
      administration for contraceptive medicines as well as between brand-name drugs,
      generics, and similares, as they are known in Brazil. It explores how Brazilian
      prescribers and users-within the divergent structural constraints afforded by
      private and public health-apprehend and negotiate distinctions between the drugs
      available to them. This ethnographic account of hormone use reveals new fault
      lines through which the pharmakon exerts its influence. The attention that
      industry places on pharmacodynamics as it produces new products from similar
      compounds suggests that pharmaceutical effects are at once symbolic and real. The
      article concludes with a reflection on the future of the generic form in a field
      increasingly crowded by branded copies. 

PMID- 25046156
TI  - Tuf of Streptococcus pneumoniae is a surface displayed human complement regulator
      binding protein.
AB  - Streptococcus pneumoniae is a Gram-positive bacterium, causing acute sinusitis,
      otitis media, and severe diseases such as pneumonia, bacteraemia, meningitis and
      sepsis. Here we identify elongation factor Tu (Tuf) as a new Factor H binding
      protein of S. pneumoniae. The surface protein PspC which also binds a series of
      other human immune inhibitors, was the first identified pneumococcal Factor H
      binding protein of S. pneumoniae. Pneumococcal Tuf, a 55 kDa pneumococcal
      moonlighting protein which is displayed on the surface of pneumococci, is also
      located in the cytoplasm and is detected in the culture supernatant. Tuf binds
      the human complement inhibitors Factor H, FHL-1, CFHR1 and also the proenzyme
      plasminogen. Factor H and FHL-1 bound to Tuf, retain their complement regulatory
      activities. Similarly, plasminogen bound to Tuf was accessible for the activator
      uPA and activated plasmin cleaved the synthetic chromogenic substrate S-2251 as
      well as the natural substrates fibrinogen and the complement proteins C3 and C3b.
      Taken together, Tuf of S. pneumoniae is a new multi-functional bacterial
      virulence factor that helps the pathogen in complement escape and likely also in
      ECM degradation.

PMID- 25046154
TI  - Eliciting neutralizing antibodies with gp120 outer domain constructs based on M
      group consensus sequence.
AB  - One strategy being evaluated for HIV-1 vaccine development is focusing immune
      responses towards neutralizing epitopes on the gp120 outer domain (OD) by
      removing the immunodominant, but non-neutralizing, inner domain. Previous OD
      constructs have not elicited strong neutralizing antibodies (nAbs). We
      constructed two immunogens, a monomeric gp120-OD and a trimeric gp120-OD*3, based
      on an M group consensus sequence (MCON6). Their biochemical and immunological
      properties were compared with intact gp120. Results indicated better preservation
      of critical neutralizing epitopes on gp120-OD*3. In contrast to previous studies,
      our immunogens induced potent, cross-reactive nAbs in rabbits. Although nAbs
      primarily targeted Tier 1 viruses, they exhibited significant breadth. Epitope
      mapping analyses indicated that nAbs primarily targeted conserved V3 loop
      elements. Although the potency and breadth of nAbs were similar for all three
      immunogens, nAb induction kinetics indicated that gp120-OD*3 was superior to
      gp120-OD, suggesting that gp120-OD*3 is a promising prototype for further gp120
      OD-based immunogen development. 

PMID- 25046157
TI  - Keratan sulfate expression is associated with activation of a subpopulation of
      microglia/macrophages in Wallerian degeneration.
AB  - Wallerian degeneration is a fundamental process of axonal degeneration distal to
      the injury site. Although axonal degeneration itself is accomplished in a few
      days, the subsequent process of removing debris, including myelin debris, in the
      central nervous system takes more time. Since this debris is a potent inhibitor
      of axonal regeneration, the removal process is critical for functional recovery
      after neuronal injuries. Although it is known that microglia/macrophages are
      involved in this process, the underlying mechanisms are not fully understood.
      Here, we found that keratan sulfate (KS) expression was induced far from the
      injury site after spinal cord injury. A hemilateral section of the spinal cord at
      the third cervical level induced KS expression in a restricted area of the
      ipsilateral column at the first lumbar level 1 week after injury. This localized
      KS expression lasted for at least 1 month after injury. The KS signal was merged
      with a portion of Iba1-positive cells, suggesting that a subpopulation of
      microglia/macrophages expressed KS. KS-positive cells expressed CD68 and CD86,
      but not CD206 or arginase 1, suggesting that these microglia/macrophages were in
      an activated state probably polarized to M1. Our study has explored for the first
      time the relation between KS expression and activation of microglia/macrophages
      in Wallerian degeneration. 

PMID- 25046158
TI  - Construction of robust dynamic genome-scale metabolic model structures of
      Saccharomyces cerevisiae through iterative re-parameterization.
AB  - Dynamic flux balance analysis (dFBA) has been widely employed in metabolic
      engineering to predict the effect of genetic modifications and environmental
      conditions in the cell's metabolism during dynamic cultures. However, the
      importance of the model parameters used in these methodologies has not been
      properly addressed. Here, we present a novel and simple procedure to identify
      dFBA parameters that are relevant for model calibration. The procedure uses
      metaheuristic optimization and pre/post-regression diagnostics, fixing
      iteratively the model parameters that do not have a significant role. We
      evaluated this protocol in a Saccharomyces cerevisiae dFBA framework calibrated
      for aerobic fed-batch and anaerobic batch cultivations. The model structures
      achieved have only significant, sensitive and uncorrelated parameters and are
      able to calibrate different experimental data. We show that consumption,
      suboptimal growth and production rates are more useful for calibrating dynamic S.
      cerevisiae metabolic models than Boolean gene expression rules, biomass
      requirements and ATP maintenance. 

PMID- 25046159
TI  - Engineering Clostridium acetobutylicum for production of kerosene and diesel
      blendstock precursors.
AB  - Processes for the biotechnological production of kerosene and diesel blendstocks
      are often economically unattractive due to low yields and product titers.
      Recently, Clostridium acetobutylicum fermentation products acetone, butanol, and
      ethanol (ABE) were shown to serve as precursors for catalytic upgrading to higher
      chain-length molecules that can be used as fuel substitutes. To produce suitable
      kerosene and diesel blendstocks, the butanol:acetone ratio of fermentation
      products needs to be increased to 2-2.5:1, while ethanol production is minimized.
      Here we show that the overexpression of selected proteins changes the ratio of
      ABE products relative to the wild type ATCC 824 strain. Overexpression of the
      native alcohol/aldehyde dehydrogenase (AAD) has been reported to primarily
      increase ethanol formation in C. acetobutylicum. We found that overexpression of
      the AAD(D485G) variant increased ethanol titers by 294%. Catalytic upgrading of
      the 824(aad(D485G)) ABE products resulted in a blend with nearly 50wt%<=C9
      products, which are unsuitable for diesel. To selectively increase butanol
      production, C. beijerinckii aldehyde dehydrogenase and C. ljungdhalii butanol
      dehydrogenase were co-expressed (strain designate 824(Cb ald-Cl bdh)), which
      increased butanol titers by 27% to 16.9gL(-1) while acetone and ethanol titers
      remained essentially unaffected. The solvent ratio from 824(Cb ald-Cl bdh)
      resulted in more than 80wt% of catalysis products having a carbon chain
      length>=C11 which amounts to 9.8gL(-1) of products suitable as kerosene or diesel
      blendstock based on fermentation volume. To further increase solvent production,
      we investigated expression of both native and heterologous chaperones in C.
      acetobutylicum. Expression of a heat shock protein (HSP33) from Bacillus
      psychrosaccharolyticus increased the total solvent titer by 22%. Co-expression of
      HSP33 and aldehyde/butanol dehydrogenases further increased ABE formation as well
      as acetone and butanol yields. HSP33 was identified as the first heterologous
      chaperone that significantly increases solvent titers above wild type C.
      acetobutylicum levels, which can be combined with metabolic engineering to
      further increase solvent production. 

PMID- 25046160
TI  - Crohn's disease evaluation and treatment: clinical decision tool.

PMID- 25046162
TI  - Correlation between intraluminal oxygen gradient and radial partitioning of
      intestinal microbiota.
AB  - BACKGROUND & AIMS: The gut microbiota is a complex and densely populated
      community in a dynamic environment determined by host physiology. We investigated
      how intestinal oxygen levels affect the composition of the fecal and mucosally
      adherent microbiota. METHODS: We used the phosphorescence quenching method and a
      specially designed intraluminal oxygen probe to dynamically quantify gut luminal
      oxygen levels in mice. 16S ribosomal RNA gene sequencing was used to characterize
      the microbiota in intestines of mice exposed to hyperbaric oxygen, human rectal
      biopsy and mucosal swab samples, and paired human stool samples. RESULTS: Average
      Po2 values in the lumen of the cecum were extremely low (<1 mm Hg). In altering
      oxygenation of mouse intestines, we observed that oxygen diffused from intestinal
      tissue and established a radial gradient that extended from the tissue interface
      into the lumen. Increasing tissue oxygenation with hyperbaric oxygen altered the
      composition of the gut microbiota in mice. In human beings, 16S ribosomal RNA
      gene analyses showed an increased proportion of oxygen-tolerant organisms of the
      Proteobacteria and Actinobacteria phyla associated with rectal mucosa, compared
      with feces. A consortium of asaccharolytic bacteria of the Firmicute and
      Bacteroidetes phyla, which primarily metabolize peptones and amino acids, was
      associated primarily with mucus. This could be owing to the presence of
      proteinaceous substrates provided by mucus and the shedding of the intestinal
      epithelium. CONCLUSIONS: In an analysis of intestinal microbiota of mice and
      human beings, we observed a radial gradient of microbes linked to the
      distribution of oxygen and nutrients provided by host tissue.

PMID- 25046163
TI  - Daclatasvir-like inhibitors of NS5A block early biogenesis of hepatitis C virus
      induced membranous replication factories, independent of RNA replication.
AB  - BACKGROUND & AIMS: Direct-acting antivirals that target nonstructural protein 5A
      (NS5A), such as daclatasvir, have high potency against the hepatitis C virus
      (HCV). They are promising clinical candidates, yet little is known about their
      antiviral mechanisms. We investigated the mechanisms of daclatasvir derivatives.
      METHODS: We used a combination of biochemical assays, in silico docking models,
      and high-resolution imaging to investigate inhibitor-induced changes in
      properties of NS5A, including its interaction with phosphatidylinositol-4 kinase
      IIIalpha and induction of the membranous web, which is the site of HCV
      replication. Analyses were conducted with replicons, infectious virus, and human
      hepatoma cells that express a HCV polyprotein. Studies included a set of
      daclatasvir derivatives and HCV variants with the NS5A inhibitor class-defining
      resistance mutation Y93H. RESULTS: NS5A inhibitors did not affect NS5A stability
      or dimerization. A daclatasvir derivative interacted with NS5A and molecular
      docking studies revealed a plausible mode by which the inhibitor bound to NS5A
      dimers. This interaction was impaired in mutant forms of NS5A that are resistant
      to daclatavir, providing a possible explanation for the reduced sensitivity of
      the HCV variants to this drug. Potent NS5A inhibitors were found to block HCV
      replication by preventing formation of the membranous web, which was not linked
      to an inhibition of phosphatidylinositol-4 kinase IIIalpha. Correlative light
      electron microscopy revealed unequivocally that NS5A inhibitors had no overall
      effect on the subcellular distribution of NS5A, but completely prevented
      biogenesis of the membranous web. CONCLUSIONS: Highly potent inhibitors of NS5A,
      such as daclatasvir, block replication of HCV RNA at the stage of membranous web
      biogenesis-a new paradigm in antiviral therapy.

PMID- 25046164
TI  - TRIM59 is up-regulated in gastric tumors, promoting ubiquitination and
      degradation of p53.
AB  - BACKGROUND & AIMS: Little is known about factors that promote gastric
      carcinogenesis. We analyzed multiple microarray data sets for messenger RNAs
      (mRNAs) that were increased significantly in human gastric tumor samples,
      compared with the adjacent normal gastric tissue. We found expression of
      tripartite motif 59 (TRIM59), which encodes a putative ubiquitin ligase, to be
      increased, and investigated its effects in gastric cancer cell lines. METHODS: We
      analyzed microarray data sets from the Oncomine database. We used quantitative
      polymerase chain reaction and immunoblotting to measure levels of TRIM59 mRNA and
      protein in 50 human gastric cancer and paired normal tissues, obtained from Renji
      Hospital and the First Affiliated Hospital of Nanchang University, in China. We
      also measured protein levels in the gastric epithelial cell line GES-1; the
      cancer cell lines MKN45, AGS, SGC7901, BGC823, Snu5, N87, and Snu1; and in tissue
      arrays of 108 human gastric tumors. TRIM59 was knocked down and overexpressed in
      gastric cancer cell lines, and the effects on proliferation, clone formation,
      migration, and growth of xenograft tumors in nude mice were assessed. TRIM59
      related signaling pathways were examined by immunoblotting and quantitative
      polymerase chain reaction. We analyzed interactions among TRIM59, P53, and
      ubiquitin in immunoprecipitation studies. RESULTS: Levels of TRIM59 mRNA and
      protein were increased significantly in gastric tumors compared with nontumor
      tissues; increased levels were associated with advanced tumor stage and shorter
      patient survival times. TRIM59 knockdown reduced proliferation, clone formation,
      and migration of gastric cancer cell lines, as well as growth of xenograft tumors
      in nude mice; overexpression of TRIM59 had the opposite effects. TRIM59
      interacted physically with P53, increasing its ubiquitination and degradation.
      Increased levels of TRIM59 in human gastric tumors correlated with reduced
      expression of P53 target genes. CONCLUSIONS: The putative ubiquitin ligase TRIM59
      is up-regulated in human gastric tumors compared with nontumor tissues. Levels of
      TRIM59 correlate with tumor progression and patient survival times. TRIM59
      interacts with P53, promoting its ubiquitination and degradation, and TRIM59
      might promote gastric carcinogenesis via this mechanism.

PMID- 25046161
TI  - Cell death and cell death responses in liver disease: mechanisms and clinical
      relevance.
AB  - Hepatocellular death is present in almost all types of human liver disease and is
      used as a sensitive parameter for the detection of acute and chronic liver
      disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and
      animal models suggest that hepatocyte death is the key trigger of liver disease
      progression, manifested by the subsequent development of inflammation, fibrosis,
      cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ
      substantially between liver diseases. Different modes of cell death such as
      apoptosis, necrosis, and necroptosis trigger specific cell death responses and
      promote progression of liver disease through distinct mechanisms. In this review,
      we first discuss molecular mechanisms by which different modes of cell death,
      damage-associated molecular patterns, and specific cell death responses
      contribute to the development of liver disease. We then review the clinical
      relevance of cell death, focusing on biomarkers; the contribution of cell death
      to drug-induced, viral, and fatty liver disease and liver cancer; and evidence
      for cell death pathways as therapeutic targets. 

PMID- 25046165
TI  - Is chronic stress during childhood associated with adult-onset vulvodynia?
AB  - BACKGROUND: Vulvodynia is an unexplained chronic vulvar pain condition. Case
      control studies provide opportunities to examine potential mechanisms by which
      vulvodynia may develop. Findings inform etiological models that can be tested in
      subsequent prospective studies. METHODS: A survey of interpersonal relationships
      and the Structured Clinical Interview for DSM-IV Axis I Disorders was
      administered to 215 case-control pairs of women with and without vulvodynia.
      Conditional logistic regression was used to examine associations between affect
      based chronic stressors (i.e., living in fear of abuse, perceived abuse, and
      antecedent mood disorders) with vulvodynia. These associations were then examined
      among women with and without a history of childhood abuse. RESULTS: Among women
      with a history of severe childhood abuse, those with vulvodynia had three times
      the odds of living in fear of any abuse compared to women without vulvodynia (95%
      confidence interval: 1.0, 11.0), after adjustment for childhood poverty. Among
      women with no history of childhood abuse, those with vulvodynia had over six
      times the odds of antecedent mood disorder compared to women without vulvodynia
      (95% confidence interval: 1.9,19.6). CONCLUSION: Our findings suggest that affect
      based chronic stressors may be important to the psychobiological mechanisms of
      vulvodynia. Prospective studies are recommended to test biopsychosocial models of
      the etiology of vulvodynia.

PMID- 25046166
TI  - Safety assessment of plant varieties using transcriptomics profiling and a one
      class classifier.
AB  - An important part of the current hazard identification of novel plant varieties
      is comparative targeted analysis of the novel and reference varieties.
      Comparative analysis will become much more informative with unbiased analytical
      approaches, e.g. omics profiling. Data analysis estimating the similarity of new
      varieties to a reference baseline class of known safe varieties would
      subsequently greatly facilitate hazard identification. Further biological and
      eventually toxicological analysis would then only be necessary for varieties that
      fall outside this reference class. For this purpose, a one-class classifier tool
      was explored to assess and classify transcriptome profiles of potato (Solanum
      tuberosum) varieties in a model study. Profiles of six different varieties, two
      locations of growth, two year of harvest and including biological and technical
      replication were used to build the model. Two scenarios were applied representing
      evaluation of a 'different' variety and a 'similar' variety. Within the model
      higher class distances resulted for the 'different' test set compared with the
      'similar' test set. The present study may contribute to a more global hazard
      identification of novel plant varieties. 

PMID- 25046167
TI  - Clinical pharmacology of ponesimod, a selective S1P1 receptor modulator, after
      uptitration to supratherapeutic doses in healthy subjects.
AB  - PURPOSE: The aim of this study was to assess in healthy subjects the safety,
      tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an oral
      selective sphingosine-1-phosphate receptor 1 (S1P1) modulator in development for
      multiple sclerosis, by using an uptitration scheme up to supratherapeutic doses.
      METHODS: This was a double-blind, placebo-controlled, randomised, parallel group,
      uptitration study. Male and female subjects received ascending oral doses of
      ponesimod (n=12) or placebo (n=4) once daily for 3 days at each dose level (10-20
      40-60-80-100mg). RESULTS: The most frequent adverse events were chest discomfort,
      headache, dizziness, dyspnoea, abdominal pain, and night sweats. Chest discomfort
      and dyspnoea were considered dose-limiting. A transient decrease in heart rate
      was observed following the first 10-mg ponesimod dose (maximum mean decrease of 9
      beats per minute (bpm) (placebo: 2 bpm)). After uptitration, effects on heart
      rate were indistinguishable from placebo. A dose-dependent effect on pulmonary
      function tests was observed and reached a plateau with 60-80 mg ponesimod
      (maximum mean decrease from baseline of 1.24l (-30.5%) in forced expiratory
      volume in 1s). A plateau in mean lymphocyte count reduction of approximately 70%
      from baseline was reached at the 40 mg dose level. Observed effects were fully
      reversible within 10days after treatment discontinuation. No relevant sex
      differences were observed. CONCLUSIONS: At supratherapeutic doses, symptoms of
      chest discomfort and dyspnoea were dose-limiting. An uptitration dosing scheme is
      to be preferred in clinical studies in patients in order to limit effects of
      ponesimod on heart rate and atrioventricular (AV) conduction.

PMID- 25046168
TI  - A new approach to predict human intestinal absorption using porcine intestinal
      tissue and biorelevant matrices.
AB  - A reliable prediction of the oral bioavailability in humans is crucial and of
      high interest for pharmaceutical and food industry. The predictive value of
      currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue
      and/or in vivo animal studies for human intestinal absorption, however, is often
      insufficient, especially when food-drug interactions are evaluated. Ideally, for
      this purpose healthy human intestinal tissue is used, but due to its limited
      availability there is a need for alternatives. The aim of this study was to
      evaluate the applicability of healthy porcine intestinal tissue mounted in a
      newly developed InTESTineTM system to predict human intestinal absorption of
      compounds with different chemical characteristics, and within biorelevant
      matrices. To that end, first, a representative set of compounds was chosen of
      which the apparent permeability (Papp) data in both Caco-2 cells and human
      intestinal tissue mounted in the Ussing chamber system, and absolute human oral
      bioavailability were reported. Thereafter, Papp values of the subset were
      determined in both porcine jejunal tissue and our own Caco-2 cells. In addition,
      the feasibility of this new approach to study regional differences (duodenum,
      jejunum, and ileum) in permeability of compounds and to study the effects of
      luminal factors on permeability was also investigated. For the latter, a
      comparison was made between the compatibility of porcine intestinal tissue, Caco
      2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells
      with biorelevant samples as collected from an in vitro dynamic gastrointestinal
      model (TIM). The results demonstrated that for the paracellularly transported
      compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are
      within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are
      beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are
      more comparable to human Papp values (9 out of 12 are within 3-fold difference),
      compared to Caco-2 Papp values (4 out of 12 are within 3-fold difference). In
      addition, for the selected hydrophilic compounds a significant increase in the
      permeability was observed from duodenum to ileum. Finally, this study indicated
      that porcine jejunal tissue segments can be used with undiluted luminal samples
      to predict human intestinal permeability and the effect of biorelevant matrices
      on this. In conclusion, viable porcine intestinal tissue mounted in the
      InTESTineTM system can be applied as a reliable tool for the assessment of
      intestinal permeability in the absence and presence of biorelevant samples. This
      would enable an accessible opportunity for a reliable prediction of human
      intestinal absorption, and the effect of luminal compounds such as digested
      foods, early in drug development.

PMID- 25046169
TI  - A method of permeabilization of Drosophila embryos for assays of small molecule
      activity.
AB  - The Drosophila embryo has long been a powerful laboratory model for elucidating
      molecular and genetic mechanisms that control development. The ease of genetic
      manipulations with this model has supplanted pharmacological approaches that are
      commonplace in other animal models and cell-based assays. Here we describe recent
      advances in a protocol that enables application of small molecules to the
      developing fruit fly embryo. The method details steps to overcome the
      impermeability of the eggshell while maintaining embryo viability. Eggshell
      permeabilization across a broad range of developmental stages is achieved by
      application of a previously described d-limonene embryo permeabilization solvent
      (EPS1) and by aging embryos at reduced temperature (18  degrees C) prior to
      treatments. In addition, use of a far-red dye (CY5) as a permeabilization
      indicator is described, which is compatible with downstream applications
      involving standard red and green fluorescent dyes in live and fixed preparations.
      This protocol is applicable to studies using bioactive compounds to probe
      developmental mechanisms as well as for studies aimed at evaluating teratogenic
      or pharmacologic activity of uncharacterized small molecules.

PMID- 25046170
TI  - Effects of the red tide dinoflagellate, Karenia brevis, on early development of
      the eastern oyster Crassostrea virginica and northern quahog Mercenaria
      mercenaria.
AB  - The brevetoxin-producing dinoflagellate, Karenia brevis, adversely affects many
      shellfish species including the commercially and ecologically important bivalve
      molluscs, the northern quahog (=hard clam) Mercenaria mercenaria and eastern
      oyster Crassostrea virginica, in the Gulf of Mexico, USA. This study assessed the
      effects of exposure of these bivalves to K. brevis during their early
      development. In separate experiments, embryos of 2-4 cell stage of M. mercenaria
      and C. virginica were exposed to both whole and lysed K. brevis cells isolated
      from Manasota Key, Florida. Low bloom concentrations of 500 to 3000 cells mL(-1)
      were simulated for 96 h. Shell length, percent abnormality (and normality), and
      percent mortality of resulting larvae were measured. Percentages were recorded
      after 6, 24, and 96 h of exposure; larval shell length was measured at 24 and 96
      h. For both quahogs and oysters, the effects of exposing embryos to K. brevis on
      all larval responses were generally dose- and time-dependent. Percent mortalities
      and abnormalities of both clam and oyster embryos increased significantly after
      only 6h of exposure to whole cells of K. brevis. For clams, these parameters were
      significantly higher in whole and lysed treatments (at 3000 cells mL(-1)) than in
      controls. Percent mortalities of oysters were significantly higher in the whole
      cell treatment (3000 cells mL(-1)) than under control conditions. After 24h of
      exposure, mean larval shell length of both bivalve species was significantly
      reduced relative to controls. This was evident for clam larvae in both the lysed
      treatment at 1500 cells mL(-1) and in whole and lysed treatments at 3000 cells
      mL(-1), and for oyster larvae in the lysed treatment at 3000 cells mL(-1). After
      96 h, both species exposed to the lysed cell treatment at 3000 cells mL(-1) had
      significantly smaller larvae compared to those in the control. Overall, lysed
      cells of K. brevis had a more pronounced effect on shell length, percent
      abnormality, and mortality in both clams and oysters than did whole cells. Given
      the fact that blooms of K. brevis overlap with the spawning periods of these two
      bivalves, and that cells of this naked dinoflagellate are readily lysed by wave
      action, these results suggest that exposure to K. brevis during the early life
      history stages of clams and oysters could adversely affect their population
      recruitment. Further, the presence of whole or lysed cells of K. brevis in
      hatcheries could have a major negative impact on production.

PMID- 25046171
TI  - The functional GRM3 Kozak sequence variant rs148754219 affects the risk of
      schizophrenia and alcohol dependence as well as bipolar disorder.

PMID- 25046172
TI  - Sex and rhythms in sandflies and mosquitoes: an appreciation of the work of
      Alexandre Afranio Peixoto (1963-2013).
AB  - I will briefly discuss the work of Alexandre A. Peixoto on sandflies and
      mosquitoes, focusing initially on his contributions to the population biology and
      phylogenetics of Brazilian populations of these important hematophagous insects.
      I shall also review some of his work on the underlying molecular clocks that
      mediate rhythmic behaviour and physiology in these species. 

PMID- 25046173
TI  - Genetic variation of human respiratory syncytial virus among children with fever
      and respiratory symptoms in Shanghai, China, from 2009 to 2012.
AB  - Human respiratory syncytial virus (HRSV) of genus Pneumovirus is one of the most
      common pathogens causing severe acute lower respiratory tract infection in
      infants and children. No information on the genotype distribution of HRSV is
      available in East China (e.g. Shanghai). From August 2009 to December 2012, 2407
      nasopharyngeal swabs were collected from outpatient children with fever and
      respiratory symptoms in Shanghai. HRSV infection was determined using a multiplex
      RT-PCR assay. The second hypervariable region (HVR2) of G protein gene of HRSV
      was amplified and sequenced from HRSV positive samples. Genotypes were
      characterized by phylogenetic analyses. Of 2407 nasopharyngeal samples, 184
      (7.6%) were tested as HRSV positive. From 160 positive subjects with sufficient
      nasopharyngeal samples, 69 HVR2 sequences were obtained by RT-PCR and sequencing.
      Three HRSV epidemic seasons were observed from August 2009 to December 2012, and
      an extreme outbreak of HRSV occurred in the 2009-2010 epidemic season. A genotype
      shift of predominant HRSV strains from B group in the 2009-2010 epidemic season
      to group A in the subsequent epidemic seasons was observed. Ten HRSV genotypes,
      including four group A genotypes NA1, NA3, NA4, and ON1, and six group B
      genotypes BA9, BA10, SAB4, CB1, BAc, and BA?, were detected in Shanghai. Seven
      genotypes (NA1, BA9-10, SAB4, CB1, BAc and BA?) were found in the 2009-2010
      epidemic season. The co-circulation of multiple genotypes was associated with the
      extreme outbreak of HRSV among children with fever and respiratory symptoms in
      the 2009-2010 epidemic season. 

PMID- 25046174
TI  - Is telemedicine an answer to reducing 30-day readmission rates post-acute
      myocardial infarction?
AB  - BACKGROUND: Patients hospitalized for an acute myocardial infarction (AMI) are at
      risk for early readmission. Readmission rates in the community reportedly reach
      approximately 20%, and 30-day readmission rates have become a quality-of-care
      marker. Telemedicine is one strategy for improving clinical outcomes by offering
      real-time biometrics tracking and rapid intervention. We retrospectively assessed
      the 30-day readmission rate of post-AMI members of a telemedicine system.
      MATERIALS AND METHODS: All "SHL"-Telemedicine subscribers who sustained an AMI
      and those who became subscribers within 10 days from discharge post-AMI between
      2009 and 2012 were assessed. Their files were reviewed for demographics, coronary
      risk factors, reasons for readmission, and discharge diagnoses. RESULTS: In
      total, 897 suitable patients (mean age, 62+/-14 years; 81% males) were included.
      They had made 3,318 calls to the monitor center for consultation. A mobile
      intensive care unit was dispatched for 158 patients, 64 were transported to the
      hospital, and 52 (5.8%) were readmitted (10 patients were readmitted twice).
      Thirty-five readmissions were for noncardiac reasons. Twelve patients had acute
      coronary syndrome (11 were revascularized). Readmission rates were higher in
      patients with repeat AMIs (11.9% versus 5.3% among those with no AMI history) and
      in females (9.6% versus 4.9% among males). Unlike published figures for the
      general population, there were no significant differences between readmitted and
      non-readmitted patients regarding diabetes, hypertension, or congestive heart
      failure. CONCLUSIONS: Telemedicine technology shows considerable promise for
      reducing 30-day readmission rates of post-AMI patients.

PMID- 25046175
TI  - Characterization of vascular complications in experimental model of fructose
      induced metabolic syndrome.
AB  - Vascular dysfunction is an important complication associated with metabolic
      syndrome (MS). Here we fully characterized vascular complications in a rat model
      of fructose-induced MS. MS was induced by adding fructose (10%) to drinking water
      to male Wistar rats of 6 weeks age. Blood pressure (BP) and isolated aorta
      responses phenylephrine (PE), KCl, acetylcholine (ACh), and sodium nitroprusside
      (SNP) were recorded after 6, 9, and 12 weeks of fructose administration. In
      addition, serum levels of glucose, insulin, uric acid, tumor necrosis factor
      alpha (TNFalpha), lipids, advanced glycation end products (AGEs), and arginase
      activity were determined. Furthermore, aortic reactive oxygen species (ROS)
      generation, hemeoxygenase-1 expression, and collagen deposition were examined.
      Fructose administration resulted in a significant hyperinslinemia after 6 weeks
      which continued for 12 weeks. It was also associated with a significant increase
      in BP after 6 weeks which was stable for 12 weeks. Aorta isolated from MS animals
      showed exaggerated contractility to PE and KCl and impaired relaxation to ACh
      compared with control after 6 weeks which were clearer at 12 weeks of fructose
      administration. In addition, MS animals showed significant increases in serum
      levels of lipids, uric acid, AGEs, TNFalpha, and arginase enzyme activity after
      12 weeks of fructose administration. Furthermore, aortae isolated from MS animals
      were characterized by increased ROS generation and collagen deposition. In
      conclusion, adding fructose (10%) to drinking water produces a model of MS with
      vascular complications after 12 weeks that are characterized by insulin
      resistance, hypertension, disturbed vascular reactivity and structure,
      hyperuricemia, dyslipidemia, and low-grade inflammation.

PMID- 25046176
TI  - Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies
      on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and
      signaling molecule. It plays a vital role in the repair of DNA strand breaks
      induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have
      the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional
      quantitative structure activity relationship (3D QSAR) models were developed
      using comparative molecular field analysis, comparative molecular similarity
      indices analysis and docking studies. A set of 88 molecules were docked into the
      active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP
      1), by a procedure called multiple receptor conformation docking (MRCD), in order
      to improve the 3D QSAR models through the analysis of binding conformations. The
      docked poses were clustered to obtain the best receptor binding conformation.
      These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD
      and QSAR information, some key features have been identified that explain the
      observed variance in the activity. Two receptor-based QSAR models were generated;
      these models showed good internal and external statistical reliability that is
      evident from the [Formula: see text], [Formula: see text] and [Formula: see
      text]. The identified key features enabled us to design new PARP-1 inhibitors.

PMID- 25046177
TI  - Plant-driven repurposing of the ancient S-adenosylmethionine repair enzyme
      homocysteine S-methyltransferase.
AB  - Homocysteine S-methyltransferases (HMTs) are widely distributed enzymes that
      convert homocysteine (Hcy) into methionine (Met) using either S
      adenosylmethionine (AdoMet) or the plant secondary product S-methylmethionine
      (SMM) as methyl donor. AdoMet is chirally and covalently unstable, with
      racemization of natural (S,S)-AdoMet yielding biologically inactive (R,S)-AdoMet
      and depurination yielding S-ribosylmethionine (S-ribosylMet). The apparently
      futile AdoMet-dependent reaction of HMTs was assigned a role in repairing chiral
      damage to AdoMet in yeast: yeast HMTs strongly prefer (R,S)- to (S,S)-AdoMet and
      thereby limit (R,S)-AdoMet build-up [Vinci and Clarke (2010) J. Biol. Chem. 285,
      20526-20531]. In the present study, we show that bacterial, plant, protistan and
      animal HMTs likewise prefer (R,S)- over (S,S)-AdoMet, that their ability to use
      SMM varies greatly and is associated with the likely prevalence of SMM in the
      environment of the organism and that most HMTs cannot use S-ribosylMet. Taken
      with results from comparative genomic and phylogenetic analyses, these data imply
      that (i) the ancestral function of HMTs was (R,S)-AdoMet repair, (ii) the
      efficient use of SMM reflects the repurposing of HMTs after the evolutionary
      advent of plants introduced SMM into the biosphere, (iii) this plant-driven
      repurposing was facile and occurred independently in various lineages, and (iv)
      HMTs have little importance in S-ribosylMet metabolism. 

PMID- 25046178
TI  - Destruction of white matter integrity in patients with mild cognitive impairment
      and Alzheimer disease.
AB  - BACKGROUND: Accumulating evidence shows that gradual loss of white matter
      integrity plays an important role in the development of Alzheimer disease (AD).
      OBJECTIVE: The aim of this research was to study the microstructural integrity of
      white matter in AD in vivo. METHODS: Global fractional anisotropy, global axial
      diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects
      with normal controls (NC), mild cognitive impairment (MCI), and AD using
      Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further
      compared specific white matter tracts among the 3 groups. RESULTS: Compared with
      the NC group, the MCI group had significantly increased global AxD and global RD.
      Compared with the NC and MCI groups, the AD group had significantly decreased
      global fractional anisotropy, increased global AxD, and increased global RD. With
      regard to specific white matter tracts, in the MCI group, we found increased AxD
      and increased RD in the external capsule, part of the lateral cholinergic
      pathway, in addition to the tracts connecting the limbic regions, predominantly
      in the left hemisphere. In the AD group, white matter abnormalities were
      widespread, including in the external capsule (cholinergic pathway) and limbic
      region tracts as well as tracts connecting anterior to posterior regions
      bilaterally. CONCLUSIONS: The radiographic manifestation of damaged white matter
      microstructural integrity in the cholinergic pathway in MCI patients may provide
      a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage
      of AD.

PMID- 25046179
TI  - Synthesis of core-shell graphitic carbon@silica nanospheres with dual-ordered
      mesopores for cancer-targeted photothermochemotherapy.
AB  - Tumor site-directed multifunctional therapeutic platforms such as
      photothermochemotherapy that respond to tumor-focused physical and biological
      stimuli are highly demanded for effective cancer therapy. Herein, targeting
      peptide-conjugated core-shell graphitic carbon@silica nanospheres with dual
      ordered mesopores (MMPS) were successfully fabricated and developed as
      antitumoral doxorubicin (DOX) delivery system (MMPSD) for synergistic targeted
      photothermal chemotherapy of breast cancer. The hydrophilic mesoporous silica
      shell guarantees good water dispersity of MMPSD. The hydrophobic graphitic
      mesoporous carbon core provides excellent hydrophobic drug loading, immediate
      contact between the drug and photothermal hotspots, and high NIR photothermal
      conversion efficiency. SP13 peptide facilitates MMPSD for targeted and enhanced
      delivery of DOX within HER2-positive SK-BR-3 breast cancer cells, while
      PEGylation ensures biocompatibility. Thus, the MMPSD system exhibited efficient
      drug loading capacity, high targeting ability, sensitive NIR/pH-responsive DOX
      release, sustained release, and excellent combined antitumor activity.

PMID- 25046181
TI  - Safety, quality, compassion... and cost.

PMID- 25046182
TI  - Locking plate fixation for proximal humerus fractures.

PMID- 25046183
TI  - Cost savings associated with a multidisciplinary protocol that expedites
      definitive fracture care.
AB  - Changes in health care reimbursement will reward systems that can improve patient
      outcomes and reduce costs. We implemented an integrated-care pathway protocol
      that coordinates the efforts of all the teams involved in the care of multiple
      trauma patients by providing standard resuscitation parameters to recommend
      timing of definitive fracture fixation. The Early Appropriate Care (EAC) protocol
      was projected to reduce complications and length of stay (LOS) in the hospital.
      We propose to calculate the projected cost savings associated with reductions in
      complications and shorter LOS from implementing the protocol. To determine
      complication rates, LOS, and costs of care, we reviewed the cases of 1114
      patients treated surgically for femur, pelvis, or acetabulum fractures between
      2000 and 2006. Complications increased LOS by 12.2 days in femur patients and
      13.8 days in pelvis and acetabulum patients. Mean additional cost per day was
      $4368 for femur patients and $4304 for pelvis/acetabulum patients. Mean cost per
      complication was $58,968 for femur patients and $98,465 for acetabulum patients.
      Projecting a 10% reduction in complications with EAC forecasts a $2,746,638 or
      $2,145,847 reduction in costs based on reduced per-complication costs or reduced
      LOS, respectively. Initial EAC implementation has resulted in fewer complications
      with an estimated annual cost reduction of $2,227,151, consistent with the
      projections. Literature review yielded cost estimates of $2480 per hospital day
      and $37,772 per complication. These literature estimates forecast total cost
      savings of $888,940 per reduction in LOS and $1,531,646 per reduction in
      complications. In spite of the wide range of estimates for the total cost
      reduction, it is clear that the reduction in costs associated with a 10%
      reduction in complications from implementing the EAC protocol will be
      substantial. Initial clinical data have shown up to 17% fewer complications with
      EAC adherence, which is projected to reduce our hospital costs by $2 million per
      year. These cost reductions justify further investment in refining the EAC
      protocol and securing hospital resources needed to support further
      implementation. 

PMID- 25046180
TI  - Mechanism of West Nile virus neuroinvasion: a critical appraisal.
AB  - West Nile virus (WNV) is an important emerging neurotropic virus, responsible for
      increasingly severe encephalitis outbreaks in humans and horses worldwide.
      However, the mechanism by which the virus gains entry to the brain
      (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and
      transneural entry have been proposed for WNV neuroinvasion, which revolve mainly
      around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal
      transport, respectively. However, an over-representation of in vitro studies
      without adequate in vivo validation continues to obscure our understanding of the
      mechanism(s). Furthermore, WNV infection in the current rodent models does not
      generate a similar viremia and character of CNS infection, as seen in the common
      target hosts, humans and horses. These differences ultimately question the
      applicability of rodent models for pathogenesis investigations. Finally, the role
      of several barriers against CNS insults, such as the blood-cerebrospinal fluid
      (CSF), the CSF-brain and the blood-spinal cord barriers, remain largely
      unexplored, highlighting the infancy of this field. In this review, a systematic
      and critical appraisal of the current evidence relevant to the possible
      mechanism(s) of WNV neuroinvasion is conducted. 

PMID- 25046184
TI  - Palmar shelf arthroplasty for rheumatoid wrist arthritis: long-term follow-up.
AB  - Rheumatoid wrist arthritis is common and affects about 1.5 million people in the
      United States. For advanced disease, arthrodesis and implant arthroplasty have
      been recommended as treatment options. In 1970, palmar shelf arthroplasty was
      introduced, and initial results were encouraging but not reproducible. In 1990,
      Dr. Skoff modified the original procedure with good results in patients followed
      for 2 to 7 years. This study reports the results of 13 patients (9 women, 4 men;
      average age, 43 years) who were followed up for an average of 13.2 years (range,
      10 to 20 years) after undergoing modified palmar shelf arthroplasty. The patients
      were interviewed and examined, and wrist radiographs were taken. The patients
      completed a questionnaire that used a 10-point pain analog scale and the Quick
      Disabilities of the Arm, Shoulder and Hand (DASH) and Modernized Activity
      Subjective Survey (MASS) Scoring Systems. Scoring results demonstrated
      improvement in pain at rest and with activity. MASS and Quick DASH scores
      improved by 76% (P < .001). Wrist range of motion averaged 35 degrees  extension
      and 32 degrees  flexion. One patient required wrist fusion; none of the remaining
      12 patients required surgical revision. Patient satisfaction was very high, and
      radiographic results demonstrated maintenance of the radiocarpal pseudarthrosis
      without ankylosis. The long-term results of modified palmar shelf arthroplasty
      demonstrated enduring analgesia and mobility without the complications of an
      implant. Modified palmar shelf arthroplasty is a reasonable surgical alternative
      for advanced rheumatoid arthritis of the wrist. 

PMID- 25046185
TI  - Harvesting bone graft from the olecranon: a quantitative and biomechanical
      comparison of proximal and dorsal cortical windows.
AB  - We conducted a study to compare 2 techniques of harvesting ulna bone graft from
      the olecranon, one using a proximal cortical window (PCW), the other using a
      dorsal cortical window (DCW), in terms of cancellous bone graft quantity and ulna
      fracture strength after graft harvest. Cancellous bone was harvested from 8 pairs
      of embalmed cadaver proximal ulna. Each side of a matched pair was randomly
      assigned to graft harvest using either a PCW or a DCW approach. Packed bone
      volume (PBV) was determined by placing the harvested bone into a 3-mL syringe and
      compacting it with a quasi-static 25-N load. Biomechanical cantilever bending was
      performed on each elbow to determine load at failure (LF). Paired Student t tests
      were used to compare PBV and LF between the experimental and control groups. The
      graft PBV obtained from the matched-pair specimens was not statistically
      different between the PCW and DCW approaches. Ulnas subjected to proximal bone
      harvest exhibited higher LF than ulnas subjected to dorsal bone harvest, though
      the difference was not statistically significant. Compared with bone graft
      harvest using the traditional DCW approach, harvest using a PCW approach provides
      similar cancellous graft amounts and exhibits similar fracture resistance. 

PMID- 25046186
TI  - Spontaneous septic arthritis of the lumbar facet caused by methicillin-resistant
      Staphylococcus aureus in an otherwise healthy adolescent.
AB  - We report the case of a 16-year-old boy with isolated septic arthritis of a
      lumbar facet. This rare presentation of an infection in a lumbar facet joint
      occurred after minor trauma sustained in a football game. Septic arthritis of the
      spinal facet joint is an uncommon phenomenon. Only 5 cases have been reported in
      immunocompromised pediatric patients. To our knowledge, no case of septic
      arthritis in an immunocompetent pediatric patient has been reported. An otherwise
      healthy 16-year-old boy presented with 4 weeks of escalating back pain after a
      minor athletics-related trauma. Evaluation showed incapacitating pain, lumbar
      musculature spasms, and the absence of fever, hemodynamic, or neurologic changes.
      Laboratory values were within normal limits. Magnetic resonance images showed a
      fluid collection within the L3-L4 facet and a localized abscess. Computed
      tomographic-guided aspiration showed methicillin-resistant Staphylococcus aureus
      infection, for which the patient received 6 weeks of vancomycin with complete
      resolution of symptoms. Refractory lumbago in an adolescent requires careful
      evaluation. 

PMID- 25046187
TI  - An indirect reduction technique for percutaneous fixation of calcaneus fractures.
AB  - We describe a positioning and indirect reduction method that allows for earlier
      fixation of some displaced calcaneus fractures. Minimally invasive surgery with
      this technique can provide good results in high-risk patients while minimizing
      soft-tissue complications. 

PMID- 25046188
TI  - The effect of 3-column spinal osteotomy on anterior pelvic plane and acetabulum
      position.
AB  - Because the spine and pelvis are integrated, changes in spine sagittal balance
      affect relative acetabulum position. A 1 degrees  change of the anterior pelvic
      plane changes acetabulum anteversion by 0.8 degrees . Three-column spine
      osteotomies correct fixed sagittal plane deformity. Twenty patients with kyphotic
      deformity and associated sagittal imbalance underwent corrective 3-column
      osteotomy. We reviewed upright pelvic and spine radiographs preoperatively and
      postoperatively and documented the changes in angles. The average sagittal
      vertical axis was 11.07 cm preoperatively and 4.8 cm postoperatively. Lumbar
      lordosis changed (on average) from 39 degrees  preoperatively to 55 degrees 
      postoperatively (P < .05). Sacral slope increased an average of 6.7 degrees  (P =
      .015). Pelvic tilt decreased by 5.4 degrees  (P = .001). The anterior pelvic
      plane increased by 8.23 degrees  (P < .0001). This correction of the sagittal
      balance is associated with a concomitant increase in sacral slope, pelvic tilt,
      and the anterior pelvic plane angles. These changes will increase acetabulum
      anteversion by a predicted 6.54 degrees . This increase will change acetabular
      cup position and must be considered in patients with spine and pelvic
      osteoarthritis that requires hip surgery.

PMID- 25046189
TI  - C7 pars fracture subadjacent to C7 pedicle screw instrumentation at the caudal
      end of a posterior cervical instrumentation construct.
AB  - We report a case of a C7 pars fracture subadjacent to C7 pedicle screw
      instrumentation at the caudal end of posterior cervical instrumentation
      construct. To date, posterior cervical instrumentation has been "off label";
      however, the US Food and Drug Administration is considering approving label
      indication of such instrumentation for this common surgical practice.
      Complications related to the techniques are reported to be relatively low. We
      know of no previous reports of pars fractures occurring subadjacent to such
      instrumentation. A 43-year-old man underwent posterior C5-C7 instrumented fusion.
      Postoperatively, the patient experienced cervical spine injury after a mechanical
      fall down stairs. Work-up detected bilateral C7 pars fractures subadjacent to the
      posterior instrumentation construct. After we treated the pars fracture with
      distal extension of the posterior fusion to the level of T2, the patient
      progressed to union and marked improvement of initial clinical symptoms that was
      maintained 2.5 years after posterior instrumentation. To our knowledge, a C7 pars
      fracture subadjacent to posterior cervical instrumentation construct has not been
      reported. We hypothesize that the pars may have been vulnerable to fracture
      because of excessive bone resection during foraminotomy or decortication. This
      complication was successfully treated by extending the fusion caudally. 

PMID- 25046190
TI  - Spontaneous resorption of a large cervical herniated nucleus pulposus.
AB  - The majority of patients with symptomatic herniated discs can be successfully and
      conservatively managed and can achieve clinical improvement without surgical
      intervention. Resorption of the herniated nucleus pulposus (HNP) is 1
      conservative mechanism for clinical improvement. We present the case of a 76-year
      old healthy man with acute cervical radicular right arm pain and positive
      Spurling test. Magnetic resonance imaging (MRI) showed a large disc extrusion
      behind the C6 vertebral body, causing severe central canal stenosis and right
      greater-than-left foraminal stenosis. The patient did not want surgical
      intervention, and his symptoms resolved with conservative treatment. A follow-up
      MRI 7 months after his initial presentation showed almost complete resorption of
      the herniated disc. The patient returned to his normal activities and has not had
      recurrence of symptoms for 2 years. This report provides an interesting example
      of complete resorption of a large, extruded cervical herniated disc in a
      symptomatic patient and a review of the literature on resorption of herniated
      discs. The review suggests that larger herniations with an epidural location
      (penetration of the posterior longitudinal ligament) have a greater chance of
      resorption. 

PMID- 25046191
TI  - Preoperative cognitive impairment and psychological distress in hospitalized
      elderly hip fracture patients.
AB  - We conducted a prospective study to evaluate the prevalence of cognitive
      impairment (CI) in elderly inpatients awaiting surgery for hip fracture, and to
      compare CI and normal cognition (NC) patients with respect to preoperative pain,
      fear, and anxiety. The study included patients who were older than 65 years when
      admitted to a hospital after acute hip fracture. Preoperative assessment involved
      use of Confusion Assessment Method-Short Form, Montreal Cognitive Assessment
      (MoCA), visual analog scales for anxiety and fear, and Wong-Baker Faces Pain
      Scale. Patients with delirium were excluded from the study. Patients with CI and
      NC, as determined by MoCA score, were compared for each assessment. Of the 65 hip
      fracture patients enrolled, 62 had evaluable cognitive data. Of these 62
      patients, 23 (37.1%) had NC (MoCA score, >= 23) and 39 (62.9%) had CI (MoCA
      score, < 23). Only 5 (7.7%) of the 65 patients had a documented diagnosis of CI
      or dementia at time of hospitalization. Mean preoperative pain scores were
      significantly (P < .001) higher for CI patients (5.3) than for NC patients (2.8).
      Our study results showed that many elderly hip fracture patients had unrecognized
      CI before surgery, and CI patients had significantly more pain than NC patients
      did. Appropriate identification of preoperative CI and treatment of pain are
      crucial in optimizing patient outcomes. 

PMID- 25046192
TI  - Dilemma of high rate of conversion from knee arthroscopy to total knee
      arthroplasty.
AB  - We tried to reduce our rate of conversion from index knee arthroscopy to total
      knee arthroplasty (TKA) for degenerative pathology (primarily meniscal) in the
      setting of coexisting arthritis in patients 50 years or older. We hypothesized
      that, by using a 2-surgeon independent evaluation method, we could reduce the
      rate to less than 10% by 3-year follow-up. Forty-two consecutive patients were
      initially evaluated by the knee replacement surgeon to determine if they were TKA
      candidates. They were then independently evaluated by another surgeon regarding
      the need for TKA and the possibility of arthroscopic debridement. The data showed
      a tendency: The under-10% target rate was nearly reached in patients younger than
      65 years (12%; 2/17) but not in patients older than 65 years (36%; 9/25). The
      overall rate of conversion to TKA was 26%. The 2 main groups (arthroscopy only,
      arthroscopy-plus-TKA) did not differ in all measured characteristics. Failure of
      our method to achieve better outcomes demonstrates that conventional criteria are
      poor in predicting which patients with meniscal pathology, which is believed to
      be relatively more symptomatic than coexisting arthritis, should avoid
      arthroscopy and go straight to TKA. 

PMID- 25046193
TI  - Neurologic complications of distal biceps tendon repair with 1-incision
      endobutton fixation.
AB  - Functional outcomes of biceps tendon rupture may be optimized with operative
      treatment. We conducted a retrospective study to determine the neurologic
      complications of using 1-incision Endobutton fixation to repair distal biceps
      tendon ruptures. Patients with distal biceps tendon ruptures treated with a 1
      incision technique and Endobutton fixation were included. The primary outcome
      measure was frequency of neurologic complications. All 50 patients in the study
      were men. Mean age was 45 years. Twenty-one patients (42%) had at least 1
      complication. Injury to the lateral antebrachial cutaneous nerve (LACN) was the
      most common (36%). Mean time to diagnosis was 17 days (range, 0 to 40 days).
      Posterior interosseous, anterior interosseous, and superficial radial nerve
      palsies each occurred at a 4% rate. Mean follow-up was 133 days. This study
      involved the largest cohort of patients with distal biceps tendon rupture
      repaired with Endobutton fixation using a 1-incision technique. The LACN injury
      rate (36%) was higher than in other studies using the same technique (0% to 22%).
      Injury rates for other neural structures near the elbow were comparable to those
      in the literature. 

PMID- 25046194
TI  - Effect of thermal processing on estimated metabolizable protein supply to dairy
      cattle from camelina seeds: relationship with protein molecular structural
      changes.
AB  - This study evaluated the effect of thermal processing on the estimated
      metabolizable protein (MP) supply to dairy cattle from camelina seeds (Camelina
      sativa L. Crantz) and determined the relationship between heat-induced changes in
      protein molecular structural characteristics and the MP supply. Seeds from two
      camelina varieties were sampled in two consecutive years and were either kept raw
      or were heated in an autoclave (moist heating) or in an air-draft oven (dry
      heating) at 120  degrees C for 1 h. The MP supply to dairy cattle was modeled by
      three commonly used protein evaluation systems. The protein molecular structures
      were analyzed by Fourier transform/infrared-attenuated total reflectance
      molecular spectroscopy. The results showed that both the dry and moist heating
      increased the contents of truly absorbable rumen-undegraded protein (ARUP) and
      total MP and decreased the degraded protein balance (DPB). However, the moist
      heated camelina seeds had a significantly higher (P < 0.05) content of ARUP and
      total MP and a significantly lower (P < 0.05) content of DPB than did the dry
      heated camelina seeds. The regression equations showed that intensities of the
      protein molecular structural bands can be used to estimate the contents of ARUP,
      MP, and DPB with high accuracy (R(2) > 0.70). These results show that protein
      molecular structural characteristics can be used to rapidly assess the MP supply
      to dairy cattle from raw and heat-treated camelina seeds. 

PMID- 25046195
TI  - Current strategies for DNA therapy based on lipid nanocarriers.
AB  - INTRODUCTION: Lipid based nanocarriers represent one of the most widely used
      strategies for the delivery of gene molecules. This review focuses on current
      strategies for the use of these nanocarriers that could open new horizons in DNA
      therapy and offer an opportunity to support the transition from resource-based
      approaches towards knowledge-based strategies. AREAS COVERED: The present review
      highlights the most promising approaches focusing on the development of safe,
      stable, and effective lipid-based carriers capable of delivering DNA to the
      proper target sites and cells. In addition, we intend to provide some insights in
      to future strategies that should be considered in order to break down barriers in
      the transformation of DNA basic-science breakthroughs into clinical applications.
      EXPERT OPINION: On the basis of the significant advances in the design of lipid
      nanocarriers our impression is that they are, with respect to other systems, in a
      'pole' position in the DNA therapy development race.

PMID- 25046196
TI  - Toward a physical interpretation of substituent effects: the case of fluorine and
      trifluoromethyl groups.
AB  - The application of ab initio and DFT computational methods at six different
      levels of theory (MP2/cc-pVDZ, MP2/aug-cc-pVTZ, B3LYP/cc-pVDZ, B3LYP/aug-cc-pVTZ,
      M06/cc-pVDZ, and M06/aug-cc-pVTZ) to meta- and para-substituted fluoro- and
      trifluoromethylbenzene derivatives and to 1-fluoro- and 1-trifluoromethyl-2
      substituted trans-ethenes allowed the study of changes in the electronic and
      geometric properties of F- and CF3-substituted systems under the impact of other
      substituents (BeH, BF2, BH2, Br, CFO, CHO, Cl, CN, F, Li, NH2, NMe2, NO, NO2, OH,
      H, CF3, and CH3). Various parameters of these systems have been investigated,
      including homodesmotic reactions in terms of the substituent effect stabilization
      energy (SESE), the pi and sigma electron donor-acceptor indexes (pEDA and sEDA,
      respectively), the charge on the substituent active region (cSAR, known earlier
      as qSAR), and bond lengths, which have been regressed against Hammett constants,
      resulting mostly in an accurate correspondence except in the case of p
      fluorobenzene derivatives. Moreover, changes in the characteristics of the
      ability of the substituent to attract or donate electrons under the impact of the
      kind of moiety to which the substituent is attached have been considered as the
      indirect substituent effect and investigated by means of the cSAR model.
      Regressions of cSAR(X) versus cSAR(Y) for any systems X and Y allow final results
      to be obtained on the same scale of magnitude. 

PMID- 25046197
TI  - Screening in pathology.

PMID- 25046198
TI  - Cervical cancer screening at crossroads.
AB  - Cervical screening has been one of the most successful public health prevention
      programmes. For 50 years, cytology formed the basis for screening, and detected
      cervical intraepithelial lesions (CIN) were treated surgically to prevent
      progression to cancer. In a high-risk country as Denmark, screening decreased the
      incidence of cervical cancer from 34 to 11 per 100,000, age-standardized rate
      (World Standard Population). Screening is, however, also expensive; Denmark
      (population: 5.6 million) undertakes close to half a million tests per year, and
      has 6-8 CIN-treated women for each prevented cancer case. The discovery of human
      papillomavirus (HPV) as the cause of cervical cancer dramatically changed
      perspectives for disease control. Screening with HPV testing was launched around
      1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized
      controlled trials (RCT) demonstrated that HPV testing provides better protection
      against cervical cancer than cytology, but it requires extra repeated testing.
      HPV vaccination RCTs, furthermore, have proved that HPV vaccination protects
      against vaccine-type high-grade CIN in women vaccinated prior to sexual activity,
      but less so in women vaccinated later. The challenge now is therefore to find an
      algorithm for screening of a heterogeneous population including non-vaccinated
      women; women vaccinated prior to start of sexual activity; and women vaccinated
      later.

PMID- 25046199
TI  - Histopathological screening for prostate carcinoma: is a benign biopsy a negative
      biopsy?
AB  - In case of clinical suspicion of a prostate malignancy, a prostate biopsy is the
      most widely used approach to confirm prostate cancer. Unfortunately, exclusion of
      prostate cancer is not feasible by means of biopsy and also the negative rate
      remains consistently high. Here, we review the information the surgical
      pathologist can still gain from a prostate biopsy in absence of overt carcinoma. 

PMID- 25046200
TI  - Using tumor phenotype, histological tumor distribution, and mammographic
      appearance to explain the survival differences between screen-detected and
      clinically detected breast cancers.
AB  - In the era of mass screening for breast cancer with mammography, it has been
      noted that conventional tumor attributes and mammographic appearance are
      insufficient to account for the better prognosis of screen-detected tumors. Such
      prognostication may require additional updated pathological information regarding
      tumor phenotype (e.g., basal status) and histological tumor distribution
      (focality). We investigated this hypothesis using a Bayesian approach to analyze
      breast cancer data from Dalarna County, Sweden. We used data for tumors diagnosed
      in the Swedish Two-County Trial and early service screening period, 1977-1995,
      and from the mature service screening period, 1996-1998. In the early period of
      mammographic screening (1977-1995), the crude hazard ratio (HR) of breast cancer
      death for screen-detected cases compared with symptomatic ones was 0.22 (95% CI:
      0.17-0.29) compared with 0.53 (95% CI: 0.34-0.76) when adjusted for conventional
      tumor attributes only. Using the data from the mature service screening period,
      1996-1998, the HR was 0.23 (95% CI: 0.08-0.44) unadjusted and 0.71 (95% CI: 0.26
      1.47) after adjustment for tumor phenotype, mammographic appearance, histological
      tumor distribution, and conventional tumor attributes. The area under the ROC
      curve (AUC) for the prediction of breast cancer deaths using these variables
      without the detection mode was 0.82, only slightly less than that observed when
      additionally including the detection mode (AUC=0.83). Using Freedman statistics,
      conventional tumor attributes and mammographic appearances explained 58% (95% CI:
      57.5-58.6%) of the difference of breast cancer survival between the screen
      detected and the clinically detected breast cancers, whereas the corresponding
      figure was increased to 77% (95% CI: 75.6-77.6%) when adding the two information
      on tumor phenotype and histological tumor distribution. The results indicated
      that conventional tumor attributes and mammographic appearance are not sufficient
      to be interim markers for explaining the survival difference between screen
      detected and clinically detected cancers in the era marked by the widespread use
      of mammography. Additional information on tumor phenotype and histological
      distribution may be added as effective interim markers for explaining the benefit
      of the early detection of breast cancer with mammography.

PMID- 25046201
TI  - Local resection of early rectal cancer.
AB  - The introduction of the National Danish screening programme for colorectal cancer
      will result in the detection of more early rectal cancers (ERC), which may be
      considered for local excision. For the low risk<=T1 cancer, the oncological
      outcome at local excision in smaller patient series has shown similar results to
      conventional surgery, but with a significantly lower rate of serious
      complications, morbidity and mortality. The challenge is correct preoperative
      staging, and a meticulous systematic histopathological staging of the excised
      specimen to distinguish the low risk from high-risk cases, where rescue surgery
      may be considered. The establishment of a regional or national clinical database
      is necessary to improve the local treatment of ERC.

PMID- 25046202
TI  - Personalized oncology: genomic screening in phase 1.
AB  - Improvements in cancer genomics and tumor biology have reinforced the evidence of
      cancer development driven by numerous genomic alterations. Advanced genomics
      technology can be used to characterize genomic alterations that potentially drive
      tumor growth. With the possibility of screening thousands of genes
      simultaneously, personalized molecular medicine has become an option. New
      treatments are being investigated in phase 1 trials around the world.
      Traditionally, the goal of phase 1 studies was to determine the optimal dose and
      assess dose-limiting toxicity of a potential new experimental drug. Only a
      limited number of patients will benefit from the treatment. However, introducing
      genomic mapping to select patients for early clinical trials with targeted
      molecular therapy according to the genomic findings, may lead to a better outcome
      for the patient, an enrichment of phase 1 trials, and thereby accelerated drug
      development. The overall advantage is to determine which mutation profiles
      correlate with sensitivity or lack of resistance to specific targeted therapies.
      The utility and current limitations of genomic screening to guide selection to
      Phase 1 clinical trial will be discussed. 

PMID- 25046204
TI  - Reproductive options for female cancer patients: balancing hope and realistic
      expectation.
AB  - PURPOSE OF REVIEW: To review currently available options in fertility
      preservation in cancer patients, report on emerging techniques, and highlight the
      importance of time sensitivity and recording of outcomes. RECENT FINDINGS:
      Fertility preservation in cancer patients is a rapidly expanding area of
      medicine. Recent success with experimental techniques such as oocyte
      cryopreservation and ovarian tissue cryopreservation exemplify the need for
      follow-up data collection. SUMMARY: Results of fertility outcomes in cancer
      patients should form an integral and important part of the pretreatment
      counselling process for cancer patients but limited published data from larger
      cohorts exist. The formation of a growing fertility preservation database would,
      therefore, allow ease of data analysis and more robust results.

PMID- 25046205
TI  - Management of melanomas of the gynaecological tract.
AB  - PURPOSE OF REVIEW: Primary melanomas originating from the gynaecological tract
      are rare and aggressive cancers. The 5-year survival is around 10%. The majority
      of tumours differ from cutaneous melanomas, which arise from the skin, by
      developing from melanocytes located in mucosal epithelium. The clinical
      behaviour, prognosis and the biology of mucosal melanomas are distinct from
      cutaneous melanomas. In this article, we summarize the current management of
      melanomas of the gynaecological tract (vulva, vagina, ovary and cervix) and
      discuss the progress in developing new treatments. RECENT FINDINGS: The
      management of mucosal melanomas has not changed substantially over the last
      decade and the prognosis remains poor. Surgery remains the primary treatment of
      choice in all localized melanomas of the genital tract. Radiotherapy and
      chemotherapy are options but have limited success for the majority of women.
      Activation of c-KIT occurs in vulvar melanomas. Clinical trials of targeted
      agents are underway. SUMMARY: As a result of the rarity of gynaecological tract
      melanomas, challenges associated with their anatomical locations and resistance
      to conventional radiotherapy and chemotherapy, this group of conditions remain
      difficult to treat and continue to have a poor prognosis. A greater understanding
      of the molecular profile of these cancers may provide promising targeted
      approaches.

PMID- 25046203
TI  - Electron paramagnetic resonance and electron-nuclear double resonance studies of
      the reactions of cryogenerated hydroperoxoferric-hemoprotein intermediates.
AB  - The fleeting ferric peroxo and hydroperoxo intermediates of dioxygen activation
      by hemoproteins can be readily trapped and characterized during cryoradiolytic
      reduction of ferrous hemoprotein-O2 complexes at 77 K. Previous cryoannealing
      studies suggested that the relaxation of cryogenerated hydroperoxoferric
      intermediates of myoglobin (Mb), hemoglobin, and horseradish peroxidase (HRP),
      either trapped directly at 77 K or generated by cryoannealing of a trapped peroxo
      ferric state, proceeds through dissociation of bound H2O2 and formation of the
      ferric heme without formation of the ferryl porphyrin pi-cation radical
      intermediate, compound I (Cpd I). Herein we have reinvestigated the mechanism of
      decays of the cryogenerated hydroperoxyferric intermediates of alpha- and beta
      chains of human hemoglobin, HRP, and chloroperoxidase (CPO). The latter two
      proteins are well-known to form spectroscopically detectable quasistable Cpds I.
      Peroxoferric intermediates are trapped during 77 K cryoreduction of oxy Mb, alpha
      chains, and beta-chains of human hemoglobin and CPO. They convert into
      hydroperoxoferric intermediates during annealing at temperatures above 160 K. The
      hydroperoxoferric intermediate of HRP is trapped directly at 77 K. All studied
      hydroperoxoferric intermediates decay with measurable rates at temperatures above
      170 K with appreciable solvent kinetic isotope effects. The hydroperoxoferric
      intermediate of beta-chains converts to the S = 3/2 Cpd I, which in turn decays
      to an electron paramagnetic resonance (EPR)-silent product at temperature above
      220 K. For all the other hemoproteins studied, cryoannealing of the hydroperoxo
      intermediate directly yields an EPR-silent majority product. In each case, a
      second follow-up 77 K gamma-irradiation of the annealed samples yields low-spin
      EPR signals characteristic of cryoreduced ferrylheme (compound II, Cpd II). This
      indicates that in general the hydroperoxoferric intermediates relax to Cpd I
      during cryoanealing at low temperatures, but when this state is not captured by
      reaction with a bound substrate, it is reduced to Cpd II by redox-active products
      of radiolysis. 

PMID- 25046206
TI  - Sustainability of key Maine Youth Overweight Collaborative improvements: a follow
      up study.
AB  - BACKGROUND: Primary care is an opportune setting to contribute to obesity
      prevention and treatment. However, there is limited evidence for effective and
      sustainable interventions in primary care. The Maine Youth Overweight
      Collaborative (MYOC) successfully affected office systems, provider behavior, and
      patient experience. The current study evaluates the effect of MYOC on provider
      knowledge, beliefs, practices, patient experience, and office systems, in 2012,
      three years postintervention. METHODS: A quasi-experimental field trial was used
      with all seven original MYOC intervention sites that participated in MYOC between
      2004 and 2009 and two non-MYOC control sites. Data from immediately post-MYOC in
      2009 served as the baseline comparison. Main outcome measures included rates of
      recording of BMI percentile in chart, weight classification, use of the 5210
      behavioral screening tool, parental reports of counseling received on 5210
      topics, and clinician reports of changes in knowledge, beliefs, and practices.
      RESULTS: Many key MYOC improvements were sustained or improved 3 years
      postintervention and demonstrated improvements, as compared to control sites.
      CONCLUSION: In an environment where obesity has become a priority for healthcare
      providers and systems, we demonstrate sustainable improvements in clinical
      decision support and family management of risk behaviors within a primary-care
      based approach to addressing overweight risk among children and youth. Some
      declines were observed for more-complex behavioral and system outcomes. Many
      opportunities for office system and provider improvements remain.

PMID- 25046207
TI  - Synthesis of aspirin-loaded polymer-silica composites and their release
      characteristics.
AB  - This study describes a novel approach to the synthesis of polymer-drug-silica
      nanocomposites via encapsulation/isolation of drug molecules, introduced into the
      polymer matrix by the silica gel. For the first time, tetraethoxysilane (TEOS)
      gelation in the vapor phase of the acidic catalyst is presented as an efficient
      method to enter the silica gel nanoparticles into the polymer-aspirin conjugate.
      The conducted studies reveal that the internal structure of the polymer carrier
      is significantly reorganized after the embedding of aspirin molecules and the
      silica gel. The total porosity of the polymer-drug-silica nanocomposites and the
      molecular structure of the silica gel embedded in the system strongly depend on
      the conditions of the silica source transformation. Additionally, the release of
      the drug was fine-tuned by adapting the conditions of hydrolysis and condensation
      of the silica gel precursor. Finally, to prove the usefulness of the proposed
      synthesis, the controlled release of aspirin from the polymer-drug-silica
      nanocomposites is demonstrated. 

PMID- 25046208
TI  - Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are increased after
      labour in foetal membranes and myometrium and are essential for TNF-alpha-induced
      expression of pro-labour mediators.
AB  - PROBLEM: Inflammation is commonly associated with preterm birth. In non
      gestational tissues, the cellular inhibitor of apoptosis protein (cIAP) 1 and 2,
      independent of their role in apoptosis, have emerged as important regulators of
      inflammation. There is, however, no data on the effect of human labour on the
      expression of cIAPs in human gestational tissues, or on their role in modulating
      TNF-alpha induced inflammation. METHOD OF STUDY: Myometrium and fetal membranes
      and myometrium were obtained from term non-labouring and labouring fetal
      membranes and myometrium. Fetal membranes were also obtained from preterm non
      labouring and labouring fetal membranes with and without histological
      chorioamnionitis. The effect of cIAP1 and cIAP2 knockdown by siRNA in myometrial
      primary cells on pro-labour mediators was also determined. RESULTS: cIAP1 and
      cIAP2 expression was significantly higher in fetal membranes and myometrium after
      spontaneous labour, in preterm fetal membranes with infection, and with LPS and
      TNF-alpha. cIAP2 expression was also higher in fetal membranes after spontaneous
      preterm labour when compared to non-labouring tissues. Knockdown of cIAP1 and
      cIAP2 in primary myometrial cells significantly decreased TNF-alpha induced
      expression and secretion of pro-inflammatory cytokines (IL-6 and IL-8);
      cyclooxygenase (COX)-2 expression and subsequent release of the prostaglandin
      PGE2 ; the expression and secretion of MMP-9; and NF-kappaB transcriptional
      activity. CONCLUSION: cIAP1 and cIAP2 are increased after labour in fetal
      membranes and myometrium and are involved in TNF-alpha induced-expression of pro
      labour mediators. Thus, cIAP1 and cIAP2 represent novel therapeutic targets for
      the prevention of spontaneous preterm birth.

PMID- 25046209
TI  - Conformations of disulfide-intact and -reduced lysozyme ions probed by proton
      transfer reactions at various temperatures.
AB  - Proton-transfer reactions of disulfide-intact and -reduced lysozyme ions (7+
      through 14+) to 2,6-dimethylpyridine were examined in the gas phase using tandem
      mass spectrometry with electrospray ionization. By changing temperature of a
      collision cell from 280 to 460 K, temperature dependence of reaction rate
      constants and branching fractions was measured. Absolute reaction rate constants
      for the protein ions of specific charge states were determined from intensities
      of parent and product ions in the mass spectra. Remarkable change was observed
      for the rate constants and distribution of product ions. The rate constants for
      disulfide-intact ions changed more drastically with change of charge states and
      temperature than those for disulfide-reduced ions. Observed branching fractions
      for parent and product ions were represented by calculated reaction rate
      constants with a scheme of sequential process. The reaction rate constants are
      closely related to conformation changes with change of temperature, which are
      profoundly influenced by amputation of disulfide bonds. 

PMID- 25046210
TI  - A comprehensive protocol for manual segmentation of the medial temporal lobe
      structures.
AB  - The present paper describes a comprehensive protocol for manual tracing of the
      set of brain regions comprising the medial temporal lobe (MTL): amygdala,
      hippocampus, and the associated parahippocampal regions (perirhinal, entorhinal,
      and parahippocampal proper). Unlike most other tracing protocols available,
      typically focusing on certain MTL areas (e.g., amygdala and/or hippocampus), the
      integrative perspective adopted by the present tracing guidelines allows for
      clear localization of all MTL subregions. By integrating information from a
      variety of sources, including extant tracing protocols separately targeting
      various MTL structures, histological reports, and brain atlases, and with the
      complement of illustrative visual materials, the present protocol provides an
      accurate, intuitive, and convenient guide for understanding the MTL anatomy. The
      need for such tracing guidelines is also emphasized by illustrating possible
      differences between automatic and manual segmentation protocols. This knowledge
      can be applied toward research involving not only structural MRI investigations
      but also structural-functional colocalization and fMRI signal extraction from
      anatomically defined ROIs, in healthy and clinical groups alike. 

PMID- 25046211
TI  - Tiotropium versus placebo for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Tiotropium is an anticholinergic agent which has gained widespread
      acceptance as a once daily maintenance therapy for symptoms and exacerbations of
      stable chronic obstructive pulmonary disease (COPD). In the past few years there
      have been several systematic reviews of the efficacy of tiotropium, however,
      several new trials have compared tiotropium treatment with placebo, including
      those of a soft mist inhaler, making an update necessary. OBJECTIVES: To evaluate
      data from randomised controlled trials (RCTs) comparing the efficacy of
      tiotropium and placebo in patients with COPD, upon clinically important
      endpoints. SEARCH METHODS: We searched the Cochrane Airways Group's Specialised
      Register of Trials (CAGR) and ClinicalTrials.gov up to February 2012. SELECTION
      CRITERIA: We included parallel group RCTs of three months or longer comparing
      treatment with tiotropium against placebo for patients with COPD. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed studies for inclusion and
      then extracted data on study quality and the outcome results. We contacted study
      authors and trial sponsors for additional information, and collected information
      on adverse effects from all trials. We analysed the data using Cochrane Review
      Manager 5, RevMan 5.2. MAIN RESULTS: This review included 22 studies of good
      methodological quality that had enrolled 23,309 participants with COPD. The
      studies used similar designs, however, the duration varied from three months to
      four years. In 19 of the studies, 18 mcg tiotropium once daily via the Handihaler
      dry powder inhaler was evaluated, and in three studies, 5 or 10 mcg tiotropium
      once daily via the Respimat soft mist inhaler was evaluated. Compared to placebo,
      tiotropium treatment significantly improved the mean quality of life (mean
      difference (MD) -2.89; 95% confidence interval (CI) -3.35 to -2.44), increased
      the number of participants with a clinically significant improvement (odds ratio
      (OR) 1.52; 95% CI 1.38 to 1.68), and reduced the number of participants with a
      clinically significant deterioration (OR 0.65; 95% CI 0.59 to 0.72) in quality of
      life (measured by the St George's Respiratory Questionnaire (SGRQ)). Tiotropium
      treatment significantly reduced the number of participants suffering from
      exacerbations (OR 0.78; 95% CI 0.70 to 0.87). This corresponds to a need to treat
      16 patients (95% CI 10 to 36) with tiotropium for a year in order to avoid one
      additional patient suffering exacerbations, based on the average placebo event
      rate of 44% from one-year studies. Tiotropium treatment led to fewer
      hospitalisations due to exacerbations (OR 0.85; 95% CI 0.72 to 1.00), but there
      was no statistically significant difference in all-cause hospitalisations (OR
      1.00; 95% CI 0.88 to 1.13) or non-fatal serious adverse events (OR 1.03; 95% CI
      0.97 to 1.10). Additionally, there was no statistically significant difference in
      all-cause mortality between the tiotropium and placebo groups (Peto OR 0.98; 95%
      CI 0.86 to 1.11). However, subgroup analysis found a significant difference
      between the studies using a dry powder inhaler and those with a soft mist inhaler
      (test for subgroup differences: P = 0.01). With the dry powder inhaler there were
      fewer deaths in the tiotropium group (Peto OR 0.92; 95% CI 0.80 to 1.05) than in
      the placebo group (yearly rate 2.8%), but with the soft mist inhaler there were
      significantly more deaths in the tiotropium group (Peto OR 1.47; 95% CI 1.04 to
      2.08) than in the placebo group (yearly rate 1.8%). It is noted that the rates of
      patients discontinuing study treatment were uneven, with significantly fewer
      participants withdrawing from tiotropium treatment than from placebo treatment
      (OR 0.66; 95% CI 0.59 to 0.73). Participants on tiotropium had improved lung
      function at the end of the study compared with those on placebo (trough forced
      expiratory volume in one second (FEV1) MD 118.92 mL; 95% CI 113.07 to 124.77).
      AUTHORS' CONCLUSIONS: This review shows that tiotropium treatment was associated
      with a significant improvement in patients' quality of life and it reduced the
      risk of exacerbations, with a number needed to treat to benefit (NNTB) of 16 to
      prevent one exacerbation. Tiotropium also reduced exacerbations leading to
      hospitalisation but no significant difference was found for hospitalisation of
      any cause or mortality. Thus, tiotropium appears to be a reasonable choice for
      the management of patients with stable COPD, as proposed in guidelines. The
      trials included in this review showed a difference in the risk of mortality when
      compared with placebo depending on the type of tiotropium delivery device used.
      However, these results have not been confirmed in a recent trial when 2.5 mcg or
      5 mcg of tiotropium via Respimat was used in a direct comparison to the 18 mcg
      Handihaler.

PMID- 25046212
TI  - Nanogold labeling of the yeast endosomal system for ultrastructural analyses.
AB  - Endosomes are one of the major membrane sorting checkpoints in eukaryotic cells
      and they regulate recycling or destruction of proteins mostly from the plasma
      membrane and the Golgi. As a result the endosomal system plays a central role in
      maintaining cell homeostasis, and mutations in genes belonging to this network of
      organelles interconnected by vesicular transport, cause severe pathologies
      including cancer and neurobiological disorders. It is therefore of prime
      relevance to understand the mechanisms underlying the biogenesis and organization
      of the endosomal system. The yeast Saccharomyces cerevisiae has been pivotal in
      this task. To specifically label and analyze at the ultrastructural level the
      endosomal system of this model organism, we present here a detailed protocol for
      the positively charged nanogold uptake by spheroplasts followed by the
      visualization of these particles through a silver enhancement reaction. This
      method is also a valuable tool for the morphological examination of mutants with
      defects in endosomal trafficking. Moreover, it is not only applicable for
      ultrastructural examinations but it can also be combined with immunogold
      labelings for protein localization investigations. 

PMID- 25046214
TI  - Differences in health behaviour between recipients of allogeneic haematopoietic
      SCT and the general population: a matched control study.
AB  - Little is known of health-relevant behaviour among long-term survivors of
      haematological disorders treated with haematopoietic SCT. This comparative cross
      sectional multicentre study aimed (1) to explore the prevalence of selected
      behaviours in this group and (2) to compare them with those of the general
      population. Self-reported data of 376 survivors (mean age: 50.4 (s.d. = 12.8);
      median 7 years postallogeneic SCT (interquartile range (IQR) = 8.9; range 1-33)
      were compared with controls derived from the Swiss Health Survey 2007 by
      propensity score matching. Survivors were more physically inactive (26.8% vs
      12.5%; P ? 0.001) and consumed fewer portions of vegetables (? 3 pieces: 10% vs
      21.6%; P < 0.001), fruits (? 3 pieces: 6.5% vs 10.6%; P < 0.001) and fish (31.2%
      vs 60.9% weekly fish dish; P < 0.001). More survivors consumed dairy products
      daily (92.5% vs 62.9%; P < 0.001), used sun protection regularly (94.5% vs 85.3%,
      P < 0.001) and had received influenza vaccinations in the past year (58.4% vs
      21.5%; P < 0.001); fewer survivors smoked (13.4% vs 35.4%; P < 0.001). Survivors'
      weekly alcohol consumption was lower (median 1.5 servings (IQR 4) vs median 4.5
      (IQR 10.3); P < 0.001). Of those taking immunosuppressants, 65.7% were non
      adherent. Similar to the general population, survivors experience problems
      executing several health-enhancing behaviours, warranting corrective
      interventions.

PMID- 25046213
TI  - Extracorporeal photopheresis combined with pentostatin in the conditioning
      regimen for canine hematopoietic cell transplantation does not prevent GVHD.
AB  - Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent
      immunomodulatory effects. We evaluated the use of these treatment modalities to
      prevent GVHD in a canine model of unrelated dog leukocyte Ag-mismatched
      hematopoietic cell transplantation, after conditioning with 920 cGy TBI. We have
      shown previously in this model that 36/40 dogs given MTX alone as postgrafting
      immunosuppression engrafted and that 25 of 40 dogs had severe GVHD and median
      survival of 21 days. In the current study, nine dogs received conditioning with
      920 cGy TBI and postgrafting MTX either with ECP on days -2 to -1 alone (n=5) or
      ECP on days -6 and -5 combined with two doses of pentostatin (days -4 to -3)
      (n=4). Seven of nine dogs achieved engraftment. Six dogs developed severe acute
      GVHD (four in the group with ECP alone and two with pentostatin and ECP). We
      failed to demonstrate a positive impact of ECP and pentostatin for the prevention
      of GVHD compared with historical control dogs.

PMID- 25046215
TI  - Immunogenicity of a live-attenuated Japanese encephalitis vaccine in children and
      adolescents after hematopoietic stem cell transplantation.
AB  - There have been no recommendations for revaccination with the Japanese
      encephalitis (JE) vaccine in post-hematopoietic stem cell transplantation (HSCT)
      patients. This study aimed to measure the immunogenic response to a live
      attenuated JE vaccine (SA 14-14-2) in post-HSCT patients. JE-specific
      neutralizing Ab titers were measured before and after the JE vaccination. The
      patients with Ab titers <10 at the 3-month time point received a second injection
      at 6 months. A total of 28 patients (male:female=11:17) with a median age of 13
      years (4-21 years) were included. The underlying diseases were thalassemia (50%)
      and hematologic malignancies (50%). Ten patients (35.7%) had Ab titers above the
      preventive level before vaccination. Nine of 18 patients (50%) seroconverted at 3
      months after a single JE vaccination, but only three of these patients had
      sustained protective Ab levels. Seven of nine patients (78%) seroconverted at 3
      months after a second JE vaccine injection, and all of these patients sustained
      protective Ab levels at 12 months. In conclusion, post-HSCT patients had low
      seroconversion rates after a single dose of the live-attenuated JE vaccine. These
      patients may require at least two doses of the JE vaccine to ensure protective Ab
      levels. 

PMID- 25046216
TI  - Conservative management of pneumatosis intestinalis after allogeneic
      hematopoietic SCT.

PMID- 25046217
TI  - A retrospective multi-centre study of the effects of allogeneic haematopoietic
      SCT on pulmonary function.

PMID- 25046218
TI  - Allogeneic hematopoietic SCT in combination with tyrosine kinase inhibitor
      treatment compared with TKI treatment alone in CML blast crisis.
AB  - CML treatment with tyrosine kinase inhibitors (TKIs) has improved many patients'
      prognosis, but during the disease's terminal phase, the blast crisis (CML-BC),
      has been disappointing. Allo-HSCT is another treatment, but survival rates are
      still disappointing. Currently, a combination of these two is suggested but with
      little evidence. This retrospective comparison reports on this combination and
      TKI alone for treatment of CML-BC. Of the 83 CML-BC patients, 45 received TKIs
      (imatinib; nilotinib or dasatinib after imatinib resistance; TKIs group) and 38
      were treated with allo-HSCT after TKI (TKIs+allo-HSCT group). Treatment success
      was measured in terms of the hematologic, cytogenic and molecular responses, and
      subject outcome. Follow-up was 30-126 months or until death. Univariate and
      multivariate analyses determined EFS and OS predictors. Allo-HSCT significantly
      improved the 4-year OS (46.7 vs 9.7%, P<0.001) and EFS (47.1 vs 6.7%, P<0.001)
      compared to TKI treatment alone. Hemoglobin <100 g/L, non-return to chronic phase
      after TKI therapy and TKI treatment alone are independent adverse predictors of
      OS and EFS. Allo-HSCT with individualized intervention after TKI therapy is
      superior to TKI alone for CML-BC.

PMID- 25046219
TI  - Pulmonary complications in hematopoietic SCT: a prospective study.
AB  - Pulmonary complications are common and often lethal in hematopoietic SCT
      recipients. The objective of this prospective interventional study was to
      evaluate the etiology, diagnostic procedures, risk factors and outcome of
      pulmonary complications in a cohort of hematopoietic SCT recipients followed up
      for 1 year. For patients suffering from a pulmonary complication, a diagnostic
      algorithm that included non-invasive and bronchoscopic procedures was performed.
      We identified 73 pulmonary complications in 169 patients: 50 (68%) were
      pneumonias; 21 (29%) were non-infectious complications and 2 (3%) were
      undiagnosed. Viruses (particularly Rhinovirus) and bacteria (particularly P.
      aeruginosa) (28 and 26%, respectively) were the most common causes of pneumonia.
      A specific diagnosis was obtained in 83% of the cases. A non-invasive test gave a
      specific diagnosis in 59% of the episodes. The diagnostic yield of bronchoscopy
      was 67 and 78% in pulmonary infections. Early bronchoscopy (?5 days) had higher
      diagnostic yield than late bronchoscopy (78 vs 23%; P=0.02) for pulmonary
      infections. Overall mortality was 22 and 32% of all fatalities were due to
      pulmonary complications. Pulmonary complications are common and constitute an
      independent risk factor for mortality, stressing the importance of an appropriate
      clinical management. 

PMID- 25046220
TI  - Association between mobilization regimen and PFS after auto-SCT for multiple
      myeloma.

PMID- 25046221
TI  - Preparation of double Pickering emulsions stabilized by chemically tailored
      nanocelluloses.
AB  - Nanocelluloses are bio-based nanoparticles of interest as stabilizers for oil-in
      water (o/w) Pickering emulsions. In this work, the surface chemistry of
      nanocelluloses of different length, nanofibrillated cellulose (NFC, long) and
      cellulose nanocrystals (CNC, short), was successfully tailored by chemical
      modification with lauroyl chloride (C12). The resulting nanofibers were less
      hydrophilic than the original and able to stabilize water-in-oil (w/o) emulsions.
      The combination of the two types of nanocelluloses (C12-modified and native) led
      to new surfactant-free oil-in-water-in-oil (o/w/o) double emulsions stabilized by
      nanocellulose at both interfaces. Characterization was performed with respect to
      droplet size distribution, droplet stability over time, and stability after
      centrifugation. Nanocellulose-based Pickering emulsions can be designed with a
      substantial degree of control, as demonstrated by the stability of the chemically
      tailored NFC double emulsions. Furthermore, it was demonstrated that increased
      nanofiber length leads to increased stability. 

PMID- 25046222
TI  - Risk of social isolation among Great East Japan Earthquake survivors living in
      tsunami-affected Ishinomaki, Japan.
AB  - OBJECTIVE: The Great East Japan Earthquake and tsunami affected approximately 53
      000 people in the city of Ishinomaki, Miyagi Prefecture. Approximately 30 000
      people were relocated to temporary/rental housing. The remainder re-inhabited
      tsunami-affected houses, and their conditions were not known. As social isolation
      could affect physical and psychological health, we investigated the risk of
      social isolation among the survivors who returned to their homes. METHODS: The
      surveyors went door-to-door to the tsunami-affected houses and interviewed each
      household between October 2011 and March 2012. The participants' risk of social
      isolation was assessed using 3 factors: whether they have (1) friends to talk
      with about their problems, (2) close neighbors, and (3) social/family
      interactions. We analyzed the groups at risk of social isolation and identified
      the related factors. RESULTS: The elderly (older than age 65 years) were more
      likely to have close neighbors and social/family interactions, as compared with
      younger persons. Persons living alone were less likely to have social/family
      interactions. Non-elderly men who were living alone were the highest proportion
      of people without social/family interactions. CONCLUSIONS: Our findings suggested
      that men, particularly those younger than age 65 years and living alone, were at
      high risk of social isolation and may need attention.

PMID- 25046223
TI  - Differential expression of glypican-1 in ameloblastoma variants.
AB  - Although benign, ameloblastomas are locally invasive and destructive tumors of
      the jawbones. The glypicans comprise a family of glycosylphosphatidylinositol
      anchored proteoglycans that, by virtue of their cell-surface localization and
      heparin sulfate chain composition, might regulate the response of cells to
      numerous heparin-binding growth factors, cell adhesion molecules, and
      extracellular matrix components. The expression of glypican-1 is differentially
      altered among different types of malignancies, suggesting a possible role in the
      tumorigenesis and biological behavior of these neoplasms. The aim of this study
      was to determine the expression of glypican-1 and then hypothesize the possible
      role that this protein may play in the biological behavior of ameloblastomas. We
      assessed the presence of glypican-1 by immunohistochemical staining analyses in a
      series of 80 cases of different types of ameloblastomas. Desmoplastic
      ameloblastomas exhibited the highest expression of glypican-1 (100%), followed by
      the peripheral (66%), solid/multicystic (51.2%), and unicystic (47.2%) types,
      showing statistically significant differences among them (P<0.001). Differences
      detected in glypican-1 expression among different subtypes of ameloblastomas,
      could be suggesting a possible association with their different biological
      behavior. 

PMID- 25046224
TI  - Stepwise expression of CDKN2A and RB1 proteins in esophageal mucosa from patients
      at high risk for squamous cell carcinoma.
AB  - Squamous cell carcinoma of the esophagus is a lethal cancer and carries a poor
      prognosis because of late diagnosis. Identification of molecular markers may aid
      early diagnosis. We assessed the expression of CDKN2A/RB1 in the esophageal
      mucosa and its association with the histology. Esophageal biopsies were collected
      from 38 patients with no esophageal lesion (group 1), from iodine-negative areas
      of 108 alcoholics/smokers (group 2), and from tumor and nontumor areas in 41
      patients with squamous cell carcinoma (group 3). The histologic diagnosis was
      compared with immunoexpression of CDKN2A/RB1. In group 1, histology showed normal
      mucosa/mild esophagitis and no expression of CDKN2A/RB1. In groups 2 and 3, the
      diagnosis was: normal mucosa (38.4%), esophagitis (44.4%), dysplasia and
      carcinoma in situ (2.8%), and carcinoma (14.3%). The immunoexpression of
      CDKN2A/RB1 increased in a stepwise manner from the normal mucosa, to esophagitis,
      dysplasia/carcinoma in situ, and carcinoma (P<0.01). CDKN2A/RB1 was not expressed
      in the esophageal mucosa of patients without risk factors. p16/pRb expression
      increased in a stepwise manner, according to the severity of histologic lesions,
      in biopsies from patients exposed to risk factors or with carcinoma. Esophageal
      mucosa exposed to risk factors with the expression of those proteins may be at
      risk for malignant transformation. 

PMID- 25046225
TI  - Constitutive expression of HIF-alpha plays a major role in generation of clear
      cell phenotype in human primary and metastatic renal carcinoma.
AB  - The extensive lipid accumulation occurring in clear-cell renal cell carcinoma
      (ccRCC) results in a clear-cell cytoplasm. Hypoxia-inducible factor alpha (HIF
      alpha) is constitutively expressed in many ccRCC and transcriptionally regulates
      >100 genes. In a recent breakthrough study, HIF-1alpha induced ccRCC in
      transgenic mice. On the basis of these findings, we developed a hypothesis that
      accounted for HIF-alpha generation of the clear-cell phenotype. The aim of the
      present study was to use immunohistochemical staining methods in tissue
      microarray to determine the extent to which the clear-cell phenotype coincided
      with HIF-alpha expression in primary and metastatic ccRCC. In addition, we
      studied whether the prolyl-hydroxylases (PHD2,3) play a role in promoting the
      elevated expression of HIF-alpha in tumor cells. The clear-cell phenotype was
      observed in all primary and metastatic cases of ccRCC examined. A total of 168
      renal cell carcinomas were evaluated by immunohistochemical methods; 141 of the
      168 (84%) tumors expressed HIF-alpha (HIF-1alpha and/or HIF-2alpha). In contrast,
      HIF-alpha was expressed in only 1 of the 23 (4%) non-ccRCCs. These data supported
      the hypothesis that in the majority of the tumors HIF-alpha expression overlapped
      with the clear-cell phenotype and was indicative of an HIF-alpha-mediated lipid
      accumulation. In a smaller percentage of ccRCC cases (16%), HIF-alpha was not
      detected in the tumor cells and suggested that lipid accumulation by HIF-alpha
      lipid-independent process. PHD3 was undetectable in both primary and metastatic
      ccRCC cases. We concluded that the undetectable PHD3 could contribute to the
      higher HIF-alpha expression in ccRCC. 

PMID- 25046226
TI  - Immunohistochemical expression of SFRP1 and SFRP3 proteins in normal and
      malignant reproductive tissues of rats and humans.
AB  - Secreted frizzled-related proteins 1 and 3 (SFRP1 and SFRP3) act as Wnt signaling
      pathway antagonists and play an important role in embryonic development and
      carcinogenesis. The aim of the present study was to analyze immunohistochemically
      the distribution of 2 SFRP family proteins, SFRP1 and SFRP3, in an experimental
      rat model, in normal and intrauterine growth-restricted (IUGR) human placentas,
      and in a subset of the corresponding human trophoblastic tumors (pure
      choriocarcinomas and mixed germ cell tumors with choriocarcinoma component). In
      rats, expression of both SFRP1 and SFRP3 was pronounced in the perimetrium and
      myometrium, whereas decidual cells showed only occasional positive cytoplasmic
      staining. The most prominent expression of both proteins was found in blood
      vessel endothelial cells. Stereological variable of volume density (Vv, mm)
      showed statistically higher expression of SFRP1 and SFRP3 in human IUGR placentas
      than in normal pregnancy placentas (P<0.0001). Compared with adjacent
      normal/benign tissues, reduced expression of SFRP1 and SFRP3 was observed in
      human trophoblastic tumors (58.5% and 31.25%, respectively), although none of the
      examined tumors exhibited complete loss of either protein. Our study indicates
      that increased expression of both SFRP1 and SFRP3 may contribute to the
      pathogenesis of IUGR placental dysfunction, whereas the loss of these proteins
      may be involved in the development of human trophoblastic tumors. 

PMID- 25046227
TI  - BRAF mutations in metastatic malignant melanoma: comparison of molecular analysis
      and immunohistochemical expression.
AB  - Melanoma is a complex genetic disease, and multiple genetic alterations have been
      reported to play a role during disease progression. The dysregulation of BRAF
      signaling has been shown to affect many molecules that promote the continual
      progression of melanoma. Oncogenic BRAF expression plays a vital role in
      promoting cell invasion and metastasis in melanoma. It is also associated with
      poor prognosis in metastatic melanoma. About 40% to 60% of cutaneous melanomas
      have BRAF mutations, and 90% of the mutations involve a specific substitution at
      codon 600 (BRAF V600E). In this study, we compared BRAF (V600E) mutation
      detection by molecular analysis with BRAF expression by immunohistochemical (IHC)
      analysis using 2 different antibodies. A total of 25 metastatic malignant
      melanomas were included in this study. 10 of the 25 (40%) cases were positive by
      molecular analysis using the COBAS 4800 BRAF V600 Real-time PCR assay, and 18 of
      the 25 (72%) cases were positive by IHC analysis with 2 different antibodies. All
      positive cases by molecular analysis were positive by both IHC stains (100%). No
      false negatives were obtained with either IHC stain. Eight of the 25 (32%) were
      false-positive by both IHC stains. This study demonstrates that IHC analysis is a
      very sensitive test for evaluation of BRAF mutations in metastatic malignant
      melanoma and may be useful as an initial screening test. 

PMID- 25046228
TI  - DNA-PKcs and Ku70 are predictive markers for poor prognosis of patients with gall
      bladder malignancies.
AB  - Gall bladder cancers (GBCs) are highly resistant to radiotherapy and
      chemotherapy. Unfortunately, the key molecular mechanisms responsible for
      therapeutic resistance have not been identified. In this study, the expression of
      DNA-PKcs and Ku70 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80
      adenocarcinomas (ACs) were examined by immunohistochemical analysis. Positive DNA
      PKcs and Ku70 expression were significantly associated with less lymph node
      metastasis, invasion, and low TNM stage of SC/ASCs and ACs. Univariate Kaplan
      Meier analysis showed that loss of DNA-PKcs and Ku70 expression significantly
      correlated with decreased survival in both SC/ASC and AC patients. Multivariate
      Cox regression analysis showed that loss of DNA-PKcs and Ku70 expression was an
      independent poor prognostic predictor in both SC/ASC and AC patients. Our study
      suggested that DNA-PKcs and Ku70 are tumor suppressors, and loss of DNA-PKcs and
      Ku70 expression is an important biological marker for metastasis, invasion, and
      prognosis of GBC. Currently, there is no implication of DNA-PKcs and Ku70
      expression in chemoresistance or radioresistance in GBC. 

PMID- 25046229
TI  - Value of GATA3 immunostaining in the diagnosis of parathyroid tumors.
AB  - GATA3 is a transcription factor that is involved in the embryonic development of
      the parathyroid glands and in adult parathyroid cell proliferation. The aim of
      this study is to investigate the expression of GATA3 in parathyroid tumors and to
      determine whether it could be used as an immunohistochemical marker for
      parathyroid differentiation in tumors. Immunoreactivity for GATA3 was nuclear and
      was demonstrated in all 10 hyperplastic parathyroid glands, 22 parathyroid
      adenomas, and 6 parathyroid carcinomas; whereas, all thyroid tumors, renal cell
      carcinomas, thymic epithelial tumors, and carcinoid tumors investigated for
      comparison purposes were negative for this marker. It is concluded that GATA3 is
      a very sensitive and relatively specific immunohistochemical marker for
      parathyroid differentiation that can assist in the differential diagnosis of
      parathyroid tumors. 

PMID- 25046230
TI  - Immunohistochemical expression of calretinin in ameloblastoma, adenomatoid
      odontogenic tumor, and keratocystic odontogenic tumor: a comparative study.
AB  - Calretinin is expressed primarily in the central and peripheral nervous system
      and extensively studied in colon adenocarcinoma and mesotheliomas. Calretinin is
      known to be expressed in the odontogenic epithelium and odontogenic tumors.
      However, the role of calretinin in the pathogenesis of odontogenic tumors is yet
      to be confirmed. Hence, the aim of the present study was to evaluate the
      expression and role of calretinin in selected odontogenic tumors. The study
      included 30 ameloblastomas, 30 adenomatoid odontogenic tumors, and 30
      keratocystic odontogenic tumors. Staining intensity, pattern, and localization of
      the immunopositive cells were determined. Statistical analysis was performed
      using Mann-Whitney U test and Kruskal-Wallis analysis of variance test. P-values
      <0.05 were considered to be statistically significant. Results showed that 90%
      ameloblastomas and 80% keratocystic odontogenic tumors were immunopositive to
      calretinin, whereas none of the adenomatoid odontogenic tumors showed reactivity.
      Intensity was higher in the ameloblastomas compared with the keratocystic
      odontogenic tumors. Statistically significant differences were observed when the
      expression of calretinin was compared, except between the ameloblastoma and
      keratocystic odontogenic tumor. However, the intensity of calretinin was
      significantly higher in the ameloblastoma when compared with the keratocystic
      odontogenic tumor. On the basis of these results, it is suggested that calretinin
      might be used as a specific immunohistochemical marker for the ameloblastomas and
      could play an important role in the differentiation of aggressiveness of
      different odontogenic tumors. Depending on the cell regulatory processes, we
      suggest a possible role of calretinin in the pathogenesis of ameloblastomas and
      have to be further studied along with other proliferative cell cycle and
      apoptotic markers with larger sample size. 

PMID- 25046231
TI  - Collagen immunostains can distinguish capsular fibrous tissue from septal
      fibrosis and may help stage liver fibrosis.
AB  - Core-needle biopsy remains essential for diagnosis of cirrhosis; however,
      evaluation of fibrosis in such biopsies is often challenging due to the
      fragmented nature of cirrhotic liver specimens. It is also common to see portions
      of liver capsules present in the biopsy which adds to the diagnostic challenge.
      The distinction between capsular/subcapsular fibrous tissue and septal fibrosis
      is critical to avoid potential overstaging of liver fibrosis. We compared the
      differential immunostaining in liver capsular and septal areas for collagens III,
      IV, V, VI, vitronectin, laminin, Orcein, and Trichrome in 15 whole sections of
      explanted cirrhotic livers and 5 simulated liver biopsies. Collagens III, IV, V,
      VI, Trichrome, and Orcein show distinct staining patterns in capsular fibrous
      tissue and septal fibrosis. Collagen IV shows strong diffuse septal staining and
      consistently weak to negative capsular staining. Collagens III and VI stain
      similar to IV for septal fibrosis, whereas collagen V, Trichrome, and Orcein show
      strong staining in both areas. Collagen IV, possibly with III or VI in addition
      to the routine Trichrome and hematoxylin and eosin stain, is useful in
      differentiating capsular fibrous tissue from septal fibrosis on challenging and
      fragmented liver biopsies. 

PMID- 25046232
TI  - Antigen unmasking induced by superheating.
AB  - This paper is dedicated to the description of superheating as a method for
      antigen retrieval. In our investigation, this antigen retrieval method was used
      on thermal plate, heating tissue sections at temperature 120 degrees  C for 90
      minutes. In the research we conducted the superheating method was applied to
      formalin-fixed paraffin-embedded tissue sections of breast tumors. The following
      monoclonal antibodies were used: estrogen receptor, progesterone receptor,
      epithelial membrane antigen, CD34, and Ki-67. With these tested antibodies we had
      good staining and no loss of tissue sections during the staining process. 

PMID- 25046233
TI  - Characterization of multi-layered fish scales (Atractosteus spatula) using
      nanoindentation, X-ray CT, FTIR, and SEM.
AB  - The hierarchical architecture of protective biological materials such as
      mineralized fish scales, gastropod shells, ram's horn, antlers, and turtle shells
      provides unique design principles with potentials for guiding the design of
      protective materials and systems in the future. Understanding the structure
      property relationships for these material systems at the microscale and nanoscale
      where failure initiates is essential. Currently, experimental techniques such as
      nanoindentation, X-ray CT, and SEM provide researchers with a way to correlate
      the mechanical behavior with hierarchical microstructures of these material
      systems1-6. However, a well-defined standard procedure for specimen preparation
      of mineralized biomaterials is not currently available. In this study, the
      methods for probing spatially correlated chemical, structural, and mechanical
      properties of the multilayered scale of A. spatula using nanoindentation, FTIR,
      SEM, with energy-dispersive X-ray (EDX) microanalysis, and X-ray CT are
      presented.

PMID- 25046234
TI  - Clinical effectiveness of non-invasive selective cryolipolysis.
AB  - BACKGROUND: Excess subcutaneous fat causes not only cosmetic issues, but also
      substantial systemic health problems. Cryolipolysis has been reported to provide
      non-invasive fat reduction that significantly reduces subcutaneous fat cells with
      controlled, localized cooling. OBJECTIVE: This study is intended to determine
      whether a cryolipolysis device can effectively reduce subcutaneous fat without
      damaging the overlying skin or causing significant side effects and ultimately
      produce improved cosmetic results. MATERIALS AND METHODS: A total of 15 patients
      participated in this study and they were treated unilaterally in a split-body
      trial manner with a non-invasive cryolipolysis device (Micool(TM), Hironic Co.,
      Seongnam, Korea). The degree of improvement was assessed by both objective and
      subjective assessments. Complications and side effects were recorded at every
      visit. RESULTS: The results of both objective and subjective assessments showed
      significant improvements in subcutaneous fat reduction without any meaningful
      complications. CONCLUSION: Non-invasive selective cryolipolysis has been reported
      to be a safe and effective treatment modality for the reduction of excess adipose
      tissue. Therefore, cryolipolysis is a promising technology that could be an
      appropriate and safe therapeutic option for subcutaneous fat reduction.

PMID- 25046236
TI  - The effectiveness of excimer laser on vitiligo treatment in comparison with a
      combination therapy of Excimer laser and tacrolimus in an Iranian population.
AB  - OBJECTIVES: Usage of 308-nm excimer laser (EL) is an effective treatment in
      vitiligo. As genetic predispositions along with type of skin and rate of sun
      exposure are known factors influencing the treatment outcomes, we tried to
      evaluate the treatment results of using 308 nm-excimer laser alone in comparison
      with the combined therapy of EL and topical tacrolimus in Iranian patients with
      vitiligo. METHODS: We reviewed the medical files of 150 patients with vitiligo
      who were referred to the Behsima Laser Center between April 2012 and April 2013.
      Seventy five patients who received combined therapy of 308 nm EL and topical
      tacrolimus three times a week entered the study. Seventy-five controls with
      matched characteristics and who received only EL were also selected. The amount
      of repigmentation was estimated by an expert dermatologist and was classified in
      5 ranks. RESULTS: In the case group, 33.3% (n: 25) showed 50-75% repigmentaion
      and 49.3% (n:37) had more than 75% response to therapy, whereas among the
      patients in the control group 29.3% (n: 22) showed no repigmentation and only 8%
      (n: 6) demonstrated more than 75% repigmentation response. The higher efficiency
      of the combination therapy on repigmentation was statistically significant (P:
      0.006). CONCLUSION: Our study shows that Iranian patients with vitiligo who
      received a combined treatment course with 308-nm EL and tacrolimus 0.1%
      experienced significantly higher levels of repigmentation in comparison with
      laser therapy alone.

PMID- 25046235
TI  - Enhancement of skin anti-inflammatory activities of Scutellaria baicalensis
      extract using a nanoencapsulation process.
AB  - In this study, we sought to increase the anti-inflammatory activity of
      Scutellaria baicalensis extracts using a nanoencapsulation process. The ethanol
      extract of Scutellaria baicalensis was encapsulated with lecithin and two other
      extracts as follows: aqueous extraction at 100  degrees C for 24 h (AE), 70%
      ethanol extracts at 80 degrees C for 24 h (EE), which were also compared as
      controls. The ethanol extract of S. baicalensis with lecithin was estimated to be
      94.3 nm while the encapsulation efficiency of the nanoparticles was measured as
      61.4% higher than other encapsulation processes. Antioxidant activity was also
      observed as 60% inhibition of DPPH radical scavenging activity, and nitric oxide
      production by RAW264.7 cells was also reduced by 5.1 MUM after the addition of
      0.5 mg/mL nanoparticles. Only 743.7 pg/mL of PGE2 was produced by RAW 264.7
      macrophages after the addition of 0.5 mg/mL of nanoparticles, as compared to
      1105.6 pg/mL and 962.3 pg/mL of PGE2 production after the addition of 1.0 mg/mL
      of aqueous and ethanol extracts, respectively. This is the first report, to our
      knowledge, of real-time penetration of nanoparticles into human fibroblasts using
      a confocal scanning microscope.

PMID- 25046237
TI  - Diagnosis and management of dermal filler complications in the perioral region.
AB  - BACKGROUND: Lip augmentation with injectable materials is a popular aesthetic
      procedure. When complications occur, patients often ignore which material was
      implanted, thus making subsequent treatments difficult. This study aims to
      present the diagnosis and management of dermal filler complications in the
      perioral region. STUDY DESIGN: The Medical charts of 26 patients with filler
      complications in the oral region were reviewed. All patients were submitted to
      High Frequency Ultrasound, often complemented by Magnetic Resonance Imaging (MRI)
      and White Blood Cell Scintigraphy, to evaluate filler characteristics and
      complication types. Antibiotic, corticosteroid or surgical treatment was
      therefore planned. RESULTS: Imaging always identified dermal fillers in the oral
      region, distinguishing among infections, fibrosis, granulomatous inflammation and
      product migration. Nine patients received surgery, ten received medical
      treatments, six received both, and one refused treatment. Eighty percent of the
      patients presented an improvement after three- year follow-up. CONCLUSIONS:
      Complications of oral region fillers are similar in clinical presentation but
      differ in etiology, therefore necessitating different clinical approaches.
      Imaging techniques add useful information for treatment planning.

PMID- 25046238
TI  - The prehospital management of suspected spinal cord injury: an update.
AB  - INTRODUCTION: Spinal cord injury (SCI) is a serious condition that may lead to
      long-term disabilities placing financial and social burden on patients and their
      families, as well as their communities. Spinal immobilization has been considered
      the standard prehospital care for suspected SCI patients. However, there is a
      lack of consensus on its beneficial impact on patients' outcome. OBJECTIVE: This
      paper reviews the current literature on the epidemiology of traumatic SCI and the
      practice of prehospital spinal immobilization. DESIGN: A search of literature was
      undertaken utilizing the online databases Ovid Medline, PubMed, CINAHL, and the
      Cochrane Library. The search included English language publications from January
      2000 through November 2012. RESULTS: The reported annual incidence of SCI ranges
      from 12.7 to 52.2 per 1 million and occurs more commonly among males than
      females. Motor vehicle collisions (MVCs) are the major reported causes of
      traumatic SCI among young and middle-aged patients, and falls are the major
      reported causes among patients older than 55. There is little evidence regarding
      the relationship between prehospital spinal immobilization and patient
      neurological outcomes. However, early patient transfer (8-24 hours) to spinal
      care units and effective resuscitation have been demonstrated to lead to better
      neurological outcomes. CONCLUSION: This review reaffirms the need for further
      research to validate the advantages, disadvantages, and the effects of spinal
      immobilization on patients' neurological outcomes.

PMID- 25046239
TI  - Theoretical study on conformation dynamics of three-station molecular shuttle in
      different environments and its influence on NMR chemical shifts and binding
      interactions.
AB  - Microscopic information on conformational flexibility and macrocycle-thread
      binding interactions is helpful in rational design of novel multistation
      molecular shuttles with interesting topology and functions. Molecular dynamics
      (MD) was applied to simulate conformational changes of thread and macrocycle of a
      three-station molecular shuttle in different chemical environments (vacuum, CD3CN
      CDCl3 solution, and crystal). In contrast with the highly distorted thread
      conformation in the gas phase and nonpolar CDCl3 solution, the solvated thread in
      CD3CN-CDCl3 (1:1) mix solvents exhibited a relatively rigid structure.
      Experimental observations of preferential binding at the protonated
      dibenzylammonium group (station I) were rationalized by quantum chemical
      calculations of macrocycle-thread binding energies at three different stations.
      The orthogonality of site-specific binding interactions at three different
      stations was also revealed by the nearly constant binding energy obtained at each
      specific recognition center with the replacement of different neighboring groups
      and terminal stoppers on the thread. Conformational flexibility has little effect
      on NMR signals of binding sites, but for some protons that are close to the
      solvent molecules in the first solvent shell, their chemical shifts are sensitive
      to the local electrostatic environment caused by nearby solvents. In crystal, pi
      stacking induced evident upfield shifts of NMR signals in comparison with the
      isolated monomer. 

PMID- 25046240
TI  - Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric
      epilepsy: a retrospective study.
AB  - Whole-exome sequencing (WES) has transformed our ability to detect mutations
      causing rare diseases. FORGE (Finding Of Rare disease GEnes) and Care4Rare Canada
      are nation-wide projects focused on identifying disease genes using WES and
      translating this technology to patient care. Rare forms of epilepsy are well
      suited for WES and we retrospectively selected FORGE and Care4Rare families with
      clinical descriptions that included childhood-onset epilepsy or seizures not part
      of a recognizable syndrome or an early-onset encephalopathy where standard-of
      care investigations were unrevealing. Nine families met these criteria and a
      diagnosis was made in seven, and potentially eight, of the families. In the eight
      families we identified mutations in genes associated with known neurological and
      epilepsy disorders: ASAH1, FOLR1, GRIN2A (two families), SCN8A, SYNGAP1 and
      SYNJ1. A novel and rare mutation was identified in KCNQ2 and was likely
      responsible for the benign seizures segregating in the family though additional
      evidence would be required to be definitive. In retrospect, the clinical
      presentation of four of the patients was considered atypical, thereby broadening
      the phenotypic spectrum of these conditions. Given the extensive clinical and
      genetic heterogeneity associated with epilepsy, our findings suggest that WES may
      be considered when a specific gene is not immediately suspected as causal. 

PMID- 25046242
TI  - Emotional expressions preferentially elicit implicit evaluations of faces also
      varying in race or age.
AB  - Both facial cues of group membership (race, age, and sex) and emotional
      expressions can elicit implicit evaluations to guide subsequent social behavior.
      There is, however, little research addressing whether group membership cues or
      emotional expressions are more influential in the formation of implicit
      evaluations of faces when both cues are simultaneously present. The current study
      aimed to determine this. Emotional expressions but not race or age cues elicited
      implicit evaluations in a series of affective priming tasks with emotional
      Caucasian and African faces (Experiments 1 and 2) and young and old faces
      (Experiment 3). Spontaneous evaluations of group membership cues of race and age
      only occurred when those cues were task relevant, suggesting the preferential
      influence of emotional expressions in the formation of implicit evaluations of
      others when cues of race or age are not salient. Implications for implicit
      prejudice, face perception, and person construal are discussed.

PMID- 25046241
TI  - Comparison of effectiveness of abrasive and enzymatic action of whitening
      toothpastes in removal of extrinsic stains - a clinical trial.
AB  - OBJECTIVE: To compare the effectiveness of abrasive component (perlite/calcium
      carbonate) and enzymatic component (papain and bromelain) of whitening toothpaste
      in removal of extrinsic stains. METHODS: This study is a randomized, triple blind
      and parallel group study in which 90 subjects aged 18-40 years were included. At
      baseline, stains scores were assessed by Macpherson's modification of Lobene
      Stain Index and subjects were randomly assigned to two groups with 45 subjects in
      each. Group 1 used whitening toothpaste with enzymatic action and group 2 with
      abrasive action. After 1 month, stain scores were assessed for the effectiveness
      of the two toothpastes and 2 months later to check the stain prevention efficacy.
      Wilcoxson's test was used to compare between baseline 1 and 2 months stain
      scores, and Mann-Witney U-test was applied for intragroup comparison. RESULTS:
      The mean baseline total stain score for the subjects allocated to the enzymatic
      toothpaste was 37.24 +/- 2.11 which reduced to 30.77 +/- 2.48 in 1 month, and for
      the abrasive paste, total stain reduced from 35.08 +/- 2.96 to 32.89 +/- 1.95.
      The reductions in total stain scores with both the pastes were significant
      compared with baseline stain scores (at 1 month Group 1, P = 0.0233 and Group 2,
      P = 0.0324; at 2 months, Group 1 P = 0.0356). Both the toothpastes proved to be
      equally good in removal of extrinsic stains; however, the enzymatic paste showed
      better results as compared to abrasive toothpaste. CONCLUSION: Whitening
      toothpaste with abrasive action and enzymatic action are equally effective in
      removal of extrinsic stains; however, whitening toothpaste with abrasive action
      needs to be used with caution.

PMID- 25046243
TI  - Emotion regulation meets emotional attention: the influence of emotion
      suppression on emotional attention depends on the nature of the distracters.
AB  - Recent evidence has suggested a crucial role of people's current goals in
      attention to emotional information. This asks for research investigating how and
      what kinds of goals shape emotional attention. The present study investigated how
      the goal to suppress a negative emotional state influences attention to emotion
      congruent events. After inducing disgust, we instructed participants to suppress
      all feelings of disgust during a subsequent dot probe task. Attention to
      disgusting images was modulated by the sort of distracter that was presented in
      parallel with disgusting imagery. When disgusting images were presented together
      with neutral images, emotion suppression was accompanied by a tendency to attend
      to disgusting images. However, when disgusting images were shown with positive
      images that allow coping with disgust (i.e., images representing cleanliness),
      attention tended away from disgusting images and toward images representing
      cleanliness. These findings show that emotion suppression influences the
      allocation of attention but that the successful avoidance of emotion-congruent
      events depends on the availability of effective distracters.

PMID- 25046244
TI  - The eyes have it: the role of attention in cognitive reappraisal of social
      stimuli.
AB  - Cognitive reappraisal (CR) is a commonly used emotion-regulation strategy that
      has been shown to influence affective, cognitive, and social outcomes. Although
      progress has been made in elucidating the mechanisms underlying CR, the role of
      attention remains unclear. In the present study, we investigated the role of
      attention in CR by tracking participants' gazes during the presentation of videos
      depicting people in negative moods. Participants were asked to attend naturally
      or to use reappraisal to increase or decrease their emotions while viewing the
      videos. After each video, they rated their negative emotion experience. Results
      showed that participants spent more time looking at the emotional regions in the
      target's face (eyes and mouth) when asked to up-regulate their emotions, compared
      with when they simply attended to the videos. The reverse pattern was found for
      down-regulation of emotions. In addition, the effects of cognitive reappraisal on
      negative emotion experience were mediated by the time spent looking at the
      emotional regions, with a stronger effect for the down-regulation instruction.
      Finally, direct effects of regulation instruction on negative emotion were
      observed even when controlling for time spent viewing emotional regions, which
      suggests that attention and CR are distinct components that uniquely influence
      negative emotions. These results complement and extend previous findings on the
      role of attention in CR, and highlight the importance of taking attentional
      mechanisms into account when designing CR training.

PMID- 25046245
TI  - Novel Mn-Ce-Ti mixed-oxide catalyst for the selective catalytic reduction of NOx
      with NH3.
AB  - Mn-Ce-Ti mixed-oxide catalyst prepared by the hydrothermal method was
      investigated for the selective catalytic reduction (SCR) of NOx with NH3 in the
      presence of oxygen. It was found that the environmentally benign Mn-Ce-Ti
      catalyst exhibited excellent NH3-SCR activity and strong resistance against H2O
      and SO2 with a broad operation temperature window, which is very competitive for
      the practical application in controlling the NOx emission from diesel engines. On
      the basis of the catalyst characterization, the dual redox cycles (Mn(4+) +
      Ce(3+) <-> Mn(3+) + Ce(4+), Mn(4+) + Ti(3+) <-> Mn(3+) + Ti(4+)) and the
      amorphous structure play key roles for the high catalytic deNOx performance.
      Diffuse reflectance infrared Fourier transform spectroscopy studies showed that
      the synergetic effect between Mn and Ce contributes to the formation of reactive
      intermediate species, thus promoting the NH3-SCR to proceed. 

PMID- 25046246
TI  - Combined treatment: impact of optimal psychotherapy and medication in bipolar
      disorder.
AB  - OBJECTIVES: The current study investigated the longitudinal course of symptoms in
      bipolar disorder among individuals receiving optimal treatment combining
      pharmacotherapy and psychotherapy, as well as predictors of the course of
      illness. METHODS: A total of 160 participants with bipolar disorder (bipolar I
      disorder: n = 115; bipolar II disorder: n = 45) received regular pharmacological
      treatment, complemented by a manualized, evidence-based psychosocial treatment -
      that is, cognitive behavioral therapy or psychoeducation. Participants were
      assessed at baseline and prospectively for 72 weeks using the Longitudinal
      Interval Follow-up Evaluation (LIFE) scale scores for mania/hypomania and
      depression, as well as comparison measures (clinicaltrials.gov identifier:
      NCT00188838). RESULTS: Over a 72-week period, patients spent a clear majority
      (about 65%) of time euthymic. Symptoms were experienced more than 50% of the time
      by only a quarter of the sample. Depressive symptoms strongly dominated over
      (hypo)manic symptoms, while subsyndromal symptoms were more common than full
      diagnosable episodes for both polarities. Mixed symptoms were rare, but present
      for a minority of participants. Individuals experienced approximately six
      significant mood changes per year, with a full relapse on average every 7.5
      months. Participants who had fewer depressive symptoms at intake, a later age at
      onset, and no history of psychotic symptoms spent more weeks well over the course
      of the study. CONCLUSIONS: Combined pharmacological and adjunctive psychosocial
      treatments appeared to provide an improved course of illness compared to the
      results of previous studies. Efforts to further improve the course of illness
      beyond that provided by current optimal treatment regimens will require a
      substantial focus on both subsyndromal and syndromal depressive symptoms.

PMID- 25046249
TI  - Solvent-dependent switch of ligand donor ability and catalytic activity of
      ruthenium(II) complexes containing pyridinylidene amide (PYA) N-heterocyclic
      carbene hybrid ligands.
AB  - Chelating ligands incorporating both N-[1-alkylpyridin-4(1H)-ylidene]amide (PYA)
      and N-heterocyclic carbene (NHC) donor sites were prepared and used for the
      synthesis of ruthenium(II) complexes. Cyclic voltammetry, NMR, and UV-vis
      spectroscopy of the complexes indicate a solvent-dependent contribution of the
      limiting resonance structures associated with the ligand in solution. The neutral
      pyridylidene imine structure is more pronounced in apolar solvents (CH2Cl2),
      while the mesoionic pyridinium amide form is predominant in polar solvents (MeOH,
      DMSO). The distinct electronic properties of these hybrid PYA-NHC ligands in
      different solvents have a direct influence on the catalytic activity of the
      ruthenium center, e.g., in the dehydrogenation of benzyl alcohol to benzaldehyde.
      The activity in different solvents qualitatively correlates with the solvent
      permittivity. 

PMID- 25046248
TI  - The role of nano-sized manganese oxides in the oxygen-evolution reactions by
      manganese complexes: towards a complete picture.
AB  - Eighteen Mn complexes with N-donor and carboxylate ligands have been synthesized
      and characterized. Three Mn complexes among them are new and are reported for the
      first time. The reactions of oxygen evolution in the presence of oxone
      (2KHSO5.KHSO4.K2SO4) and cerium(iv) ammonium nitrate catalyzed by these complexes
      are studied and characterized by UV-visible spectroscopy, X-ray diffraction
      spectrometry, dynamic light scattering, Fourier transform infrared spectroscopy,
      electron paramagnetic resonance spectroscopy, transmission electron microscopy,
      scanning electron microscopy, membrane-inlet mass spectrometry and
      electrochemistry. Some of these complexes evolve oxygen in the presence of oxone
      as a primary oxidant. CO2 and MnO4(-) are other products of these reactions.
      Based on spectroscopic studies, the true catalysts for oxygen evolution in these
      reactions are different. We proposed that for the oxygen evolution reactions in
      the presence of oxone, the true catalysts are both high valent Mn complexes and
      Mn oxides, but for the reactions in the presence of cerium(iv) ammonium nitrate,
      the active catalyst is most probably a Mn oxide. 

PMID- 25046250
TI  - Rational design of a thermalresponsive-polymer-switchable FRET system for
      enhancing the temperature sensitivity of upconversion nanophosphors.
AB  - Here we propose a thermoresponsive polymer PNIPAM modulated fluorescence
      resonance energy transfer (FRET) system to enhance the temperature sensitivity of
      upconversion nanophosphors (UCNPs). By utilizing red/near-infrared dual emitting
      NaLuF4:Mn(2+),Ln(3+) (Ln(3+) = Yb(3+), Er(3+), Tm(3+)) UCNPs as the energy donor
      and Au nanoparticles as the acceptor, the temperature resolution of the UCNPs is
      significantly increased from 3.1  degrees C to 0.9  degrees C in the
      physiological temperature range. Conjugating the UCNPs and acceptors into
      discrete nanocomposites in our samples facilitates reversible regulation of the
      emission intensity of UCNPs, which thus would extend their application range in
      biosensing, especially for probing the dynamic changes of local micro
      environments in biological tissues. As there are a broad variety of stimuli to
      which smart polymers can reversibly respond, our experiments are also extendable
      to various external conditions in local micro-environments, such as pH values,
      metal ions, glucose, and tissue-specific enzymes. 

PMID- 25046247
TI  - Fibroblast activation protein protects bortezomib-induced apoptosis in multiple
      myeloma cells through beta-catenin signaling pathway.
AB  - Multiple myeloma (MM) is a malignant plasma cells proliferative disease. The
      intricate cross-talk of myeloma cells with bone marrow microenvironment plays an
      important role in facilitating growth and survival of myeloma cells. Bone marrow
      mesenchymal stem cells (BMMSCs) are important cells in MM microenvironment. In
      solid tumors, BMMSCs can be educated by tumor cells to become cancer-associated
      fibroblasts (CAFs) with high expression of fibroblast activation protein (FAP).
      FAP was reported to be involved in drug resistance, tumorigenesis, neoplastic
      progression, angiogenesis, invasion, and metastasis of tumor cells. However, the
      expression and the role of FAP in MM bone marrow microenvironment are still less
      known. The present study is aimed to investigate the expression of FAP, the role
      of FAP, and its relevant signaling pathway in regulating apoptosis induced by
      bortezomib in MM cells. In this study, our data illustrated that the expression
      levels of FAP were not different between the cultured BMMSCs isolated from MM
      patients and normal donors. The expression levels of FAP can be increased by
      tumor cells conditioned medium (TCCM) stimulation or coculture with RPMI8226
      cells. FAP has important role in BMMSCs mediated protecting MM cell lines from
      apoptosis induced by bortezomib. Further study showed that this process may
      likely through beta-catenin signaling pathway in vitro. The activation of beta
      catenin in MM cell lines was dependent on direct contact with BMMSCs other than
      separated by transwell or additional condition medium from BMMSCs and cytokines. 

PMID- 25046251
TI  - Designing mechanomutable composites: reconfiguring the structure of nanoparticle
      networks through mechanical deformation.
AB  - Via a new dynamic, three-dimensional computer model, we simulate the tensile
      deformation of polymer-grafted nanoparticles that are cross-linked by labile
      bonds, which can readily rupture and reform. For a range of relatively high
      strains, the network does not fail, but rather restructures into a stable,
      ordered structure. Within this network, the reshuffling of the labile bonds
      enables the formation of this new morphology. The results provide guidelines for
      designing mechano-responsive hybrid materials that undergo controllable
      structural transitions through the application of applied forces. 

PMID- 25046252
TI  - Evidences of endocytosis via caveolae following blood-brain barrier breakdown by
      Phoneutria nigriventer spider venom.
AB  - Spider venoms contain neurotoxic peptides aimed at paralyzing prey or for defense
      against predators; that is why they represent valuable tools for studies in
      neuroscience field. The present study aimed at identifying the process of
      internalization that occurs during the increased trafficking of vesicles caused
      by Phoneutria nigriventer spider venom (PNV)-induced blood-brain barrier (BBB)
      breakdown. Herein, we found that caveolin-1alpha is up-regulated in the
      cerebellar capillaries and Purkinje neurons of PNV-administered P14 (neonate) and
      8- to 10-week-old (adult) rats. The white matter and granular layers were regions
      where caveolin-1alpha showed major upregulation. The variable age played a role
      in this effect. Caveolin-1 is the central protein that controls caveolae
      formation. Caveolar-specialized cholesterol- and sphingolipid-rich membrane sub
      domains are involved in endocytosis, transcytosis, mechano-sensing, synapse
      formation and stabilization, signal transduction, intercellular communication,
      apoptosis, and various signaling events, including those related to calcium
      handling. PNV is extremely rich in neurotoxic peptides that affect glutamate
      handling and interferes with ion channels physiology. We suggest that the PNV
      induced BBB opening is associated with a high expression of caveolae frame
      forming caveolin-1alpha, and therefore in the process of internalization and
      enhanced transcytosis. Caveolin-1alpha up-regulation in Purkinje neurons could be
      related to a way of neurons to preserve, restore, and enhance function following
      PNV-induced excitotoxicity. The findings disclose interesting perspectives for
      further molecular studies of the interaction between PNV and caveolar specialized
      membrane domains. It proves PNV to be excellent tool for studies of transcytosis,
      the most common form of BBB-enhanced permeability. 

PMID- 25046253
TI  - miR-542-3p exerts tumor suppressive functions in neuroblastoma by downregulating
      Survivin.
AB  - MicroRNAs (miRNAs) are deregulated in a variety of human cancers, including
      neuroblastoma, the most common extracranial tumor of childhood. We previously
      reported a signature of 42 miRNAs to be highly predictive of neuroblastoma
      outcome. One miRNA in this signature, miR-542, was downregulated in tumors from
      patients with adverse outcome. Reanalysis of quantitative PCR and next-generation
      sequencing transcript data revealed that miR-542-5p as well as miR-542-3p
      expression is inversely correlated with poor prognosis in neuroblastoma patients.
      We, therefore, analyzed the function of miR-542 in neuroblastoma tumor biology.
      Ectopic expression of miR-542-3p in neuroblastoma cell lines reduced cell
      viability and proliferation, induced apoptosis and downregulated Survivin.
      Survivin expression was also inversely correlated with miR-542-3p expression in
      primary neuroblastomas. Reporter assays confirmed that miR-542-3p directly
      targeted Survivin. Downregulating Survivin using siRNA copied the phenotype of
      miR-542-3p expression in neuroblastoma cell lines, while cDNA-mediated ectopic
      expression of Survivin partially rescued the phenotype induced by miR-542-3p
      expression. Treating nude mice bearing neuroblastoma xenografts with miR-542-3p
      loaded nanoparticles repressed Survivin expression, decreased cell proliferation
      and induced apoptosis in the respective xenograft tumors. We conclude that miR
      542-3p exerts its tumor suppressive function in neuroblastoma, at least in part,
      by targeting Survivin. Expression of miR-542-3p could be a promising therapeutic
      strategy for treating aggressive neuroblastoma. 

PMID- 25046254
TI  - The cooperative behaviour of antimicrobial peptides in model membranes.
AB  - A systematic analysis of the hypothesis of the antimicrobial peptides' (AMPs)
      cooperative action is performed by means of full atomistic molecular dynamics
      simulations accompanied by circular dichroism experiments. Several AMPs from the
      aurein family (2.5,2.6, 3.1), have a similar sequence in the first ten amino
      acids, are investigated in different environments including aqueous solution,
      trifluoroethanol (TFE), palmitoyloleoylphosphatidylethanolamine (POPE), and
      palmitoyloleoylphosphatidylglycerol (POPG) lipid bilayers. It is found that the
      cooperative effect is stronger in aqueous solution and weaker in TFE. Moreover,
      in the presence of membranes, the cooperative effect plays an important role in
      the peptide/lipid bilayer interaction. The action of AMPs is a competition of the
      hydrophobic interactions between the side chains of the peptides and the
      hydrophobic region of lipid molecules, as well as the intra peptide interaction.
      The aureins 2.5-COOH and 2.6-COOH form a hydrophobic aggregate to minimize the
      interaction between the hydrophobic group and the water. Once that the peptides
      reach the water/lipid interface the hydrophobic aggregate becomes smaller and the
      peptides start to penetrate into the membrane. In contrast, aurein 3.1-COOH forms
      only a transient aggregate which disintegrates once the peptides reached the
      membrane, and it shows no cooperativity in membrane penetration. 

PMID- 25046255
TI  - Age-related differences in strain rate tensor of the medial gastrocnemius muscle
      during passive plantarflexion and active isometric contraction using velocity
      encoded MR imaging: potential index of lateral force transmission.
AB  - PURPOSE: The strain rate (SR) tensor measures the principal directions and
      magnitude of the instantaneous deformation; this study aims to track age-related
      changes in the 2D SR tensor in the medial gastrocnemius during passive joint
      rotation and active isometric contraction. METHODS: SR tensors were derived from
      velocity encoded magnetic resonance phase-contrast images in nine young (28
      years) and eight senior (78 years) women. Strain rates along and in the cross
      section of the fiber were calculated from the SR tensor and used to derive the
      out-plane SR. Age-related and regional differences in the SR eigenvalues,
      orientation, and the angle between the SR and muscle fiber (SR-fiber angle) were
      statistically analyzed. RESULTS: SR along the fiber was significantly different
      between the cohorts during isometric contraction with higher values in the young
      (P < 0.05). The SR-fiber angle was larger in the young for both motion types but
      this difference was not statistically significant. Significant regional
      differences in the SR indices was seen in passive joint rotation (P < 0.05) for
      both cohorts. CONCLUSION: SR mapping reflects age-related and regional
      differences during active and passive motion respectively; this may arise from
      differences in contractility (active motion) and elastic properties (active and
      passive motion).

PMID- 25046257
TI  - What is new in genetics and osteogenesis imperfecta classification?
AB  - OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI)
      and update of its classification. SOURCES: Literature review in the PubMed and
      OMIM databases, followed by selection of relevant references. SUMMARY OF THE
      FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes
      based on clinical features and disease severity: OI type I, mild, common, with
      blue sclera; OI type II, perinatal lethal form; OI type III, severe and
      progressively deforming, with normal sclera; and OI type IV, moderate severity
      with normal sclera. Approximately 90% of individuals with OI are heterozygous for
      mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or
      sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10,
      LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes,
      associated with recessive OI and mutation in the IFITM5 gene associated with
      dominant OI. Mutations in PLS3 were recently identified in families with
      osteoporosis and fractures, with X-linked inheritance pattern. In addition to the
      genetic complexity of the molecular basis of OI, extensive phenotypic variability
      resulting from individual loci has also been documented. CONCLUSIONS: Considering
      the discovery of new genes and limited genotype-phenotype correlation, the use of
      next-generation sequencing tools has become useful in molecular studies of OI
      cases. The recommendation of the Nosology Group of the International Society of
      Skeletal Dysplasias is to maintain the classification of Sillence as the
      prototypical form, universally accepted to classify the degree of severity in OI,
      while maintaining it free from direct molecular reference.

PMID- 25046256
TI  - Effects of therapeutic approach on the neonatal evolution of very low birth
      weight infants with patent ductus arteriosus.
AB  - OBJECTIVE: To analyze the effects of treatment approach on the outcomes of
      newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from
      the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary
      dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of
      prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring
      surgery (NECsur), and death/BPD. METHODS: This was a multicentric, cohort study,
      retrospective data collection, including newborns (BW < 1000 g) with gestational
      age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal
      units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were
      transferred until the third day of life, and those with presence of congenital
      malformation or infection were excluded. Groups: G1 - conservative approach
      (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 -
      surgical ligation (independent of previous treatment). Factors analyzed:
      antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male
      gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II),
      respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation
      (MV), surfactant (< 2 h of life), and time of MV. OUTCOMES: death, O2 dependence
      at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks.
      STATISTICS: Student's t-test, chi-squared test, or Fisher's exact test; Odds
      ratio (95% CI); logistic binary regression and backward stepwise multiple
      regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p
      values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns
      were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%),
      and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the
      lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were
      observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2
      (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34;
      95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks.
      CONCLUSION: The conservative approach of PDA was associated to high mortality,
      the surgical approach to the occurrence of BPD36wks and ROPsur, and the
      pharmacological treatment was protective for the outcome death/BPD36wks.

PMID- 25046258
TI  - Nuclear abnormalities in cells from nasal epithelium: a promising assay to
      evaluate DNA damage related to air pollution in infants.
AB  - OBJECTIVES: This study intends to provide a quick, easy, and inexpensive way to
      assess nuclear abnormalities such as micronuclei and bud frequencies;
      binucleated, karyorrhectic, karyolytic, pycnotic, and condensed chromatin cells
      in nasal scrapings of infants, which are particularly important for conducting
      genotoxic studies related to the inhaled atmosphere in pediatric populations.
      METHODS: Nasal swab samples were collected from 40 infants under 12 months of age
      using a small cytobrush. 2,000 cells from each infant sample were analyzed and
      classified according to the frequency of nuclear abnormalities. RESULTS: Rates of
      nuclear abnormalities found agree with values reported in other studies of
      neonates and children. This study found 0.13% of cells with micronuclei; 1.20%
      karyorrhexis; 0.03% pyknosis; 10.85% karyolysis; 1.11% condensed chromatin; 0.54
      binucleated cells; and 0.02% nuclear bud. Differences were not observed between
      genders or environmental passive smoking, nor was any age correlation found.
      CONCLUSION: The assay proposed here is suitable for assessing the frequency of
      nuclear abnormalities from nasal cells in infants.

PMID- 25046259
TI  - Prevalence of asthma and allergic diseases in adolescents: nine-year follow-up
      study (2003-2012).
AB  - OBJECTIVE: To determine the prevalence of symptoms of asthma, rhinitis, and
      atopic eczema in adolescents (AD; 13-14 years) living in seven Brazilian cities,
      by applying the standardized written questionnaire (WQ) of the International
      Study of Asthma and Allergies in Childhood (ISAAC), and to evaluate the time
      trend nine years after the last assessment of ISAAC phase 3 (ISP3). METHODS: The
      ISAAC-WQ was answered by 20,099 AD from the Northern, Northeastern, Southeastern,
      and Southern Brazilian regions. Values obtained were compared to those observed
      in ISP3 using nonparametric (chi-squared or Fisher) tests, and the ratio of
      annual increment/decrement was established for each of the centers, according to
      the symptom assessed. RESULTS: Considering the national data and comparing to
      values of ISP3, there was a decrease in the mean prevalence of active asthma
      (18.5% vs. 17.5%) and an increase in the frequency of severe asthma (4.5% vs.
      4.7%) and physician-diagnosed asthma (14.3% vs. 17.6%). An increase in prevalence
      of rhinitis, rhinoconjunctivitis, and atopic eczema was also observed.
      CONCLUSIONS: The prevalence of asthma, rhinitis, and atopic eczema in Brazil was
      variable; higher prevalence values, especially of asthma and eczema, were
      observed in regions located closer to the Equator.

PMID- 25046265
TI  - Effects of adeno-associated virus serotype and tissue-specific expression on
      circulating biomarkers of propionic acidemia.
AB  - Propionic acidemia (PA) is an autosomal recessive inborn error of metabolism
      caused by deficiency of propionyl-CoA carboxylase (PCC). This enzyme is composed
      of six PCCA and six PCCB subunits and mediates a critical step in catabolism of
      odd chain fatty acids and certain amino acids. Current treatment options for PA
      are limited to stringent dietary restriction of protein consumption and some
      patients undergo elective liver transplantation. We previously generated a
      hypomorphic model of PA, designated Pcca(-/-)(A138T), with 2% of wild-type enzyme
      activity that mimics many aspects of the human disease. In this study, we used
      the differing tissue tropisms of adeno-associated virus (AAV) to probe the
      ability of liver or muscle-directed gene therapy to treat systemic aspects of
      this disease that affects many cell types. Systemic therapy with muscle-biased
      AAV1, liver-biased AAV8, and broadly tropic AAVrh10 mediated significant
      biochemical corrections in circulating propionylcarnitine (C3) and methyl citrate
      by all vectors. The innate tissue bias of AAV1 and AAV8 gene expression was made
      more specific by the use of muscle-specific muscle creatine kinase (specifically
      MCK6) and hepatocyte-specific transthyretin (TTR) promoters, respectively. Under
      these targeted conditions, both vectors mediated significant long-term correction
      of circulating metabolites, demonstrating that correction of muscle and likely
      other tissue types in addition to liver is necessary to fully correct pathology
      caused by PA. Liver-specific AAV8-TTR-PCCA mediated better correction than AAV1
      MCK-PCCA. These data suggest that targeted gene therapy may be a viable
      alternative to liver transplantation for PA. They also demonstrate the effects of
      tissue-specific and broad gene therapy on a cell autonomous systemic genetic
      disease.

PMID- 25046266
TI  - Synthesis, solution-processed thin film transistors and solid solutions of
      silylethynylated diazatetracenes.
AB  - Silylethynylated diazatetracenes were synthesized in a more efficient way and
      applied as n-type semiconductors in solution-processed thin film transistors with
      an electron mobility of 0.65 cm(2) V(-1) s(-1). Co-crystallization of these
      diazatetracenes with silylethynylated tetracene resulted in solid solutions,
      which exhibited interesting electrical and optical properties. 

PMID- 25046267
TI  - Ultrasound-guided botulinum toxin injections in neurology: technique, indications
      and future perspectives.
AB  - Botulinum toxin (BT) therapy is used in neurology to treat muscle hyperactivity
      disorders including dystonia, spasticity, cerebral palsy, hemifacial spasms and
      re-innervation synkinesias as well as exocrine gland hyperactivity disorders. To
      increase its therapeutic effect and to decrease adverse effects in adjacent
      tissues, exact BT placement is important. Ultrasonography (US) allows non
      invasive, real-time imaging of muscular and glandular tissues and their
      surrounding structures. It can visualize, guide, and standardize the entire
      procedure of BT application. Small randomized studies suggest that US-guidance
      can improve therapeutic efficacy and reduce adverse effects of BT therapy when
      compared to conventional placement. US-guidance should be used in forearm muscles
      when functionality is important, and in selected leg muscles. It may be used for
      targeting distinct neck muscles in cervical dystonia. It is helpful for targeting
      the salivary glands. Here we review the technique, indications and future
      developments of US-guidance for BT injection in neurological disorders. 

PMID- 25046268
TI  - PCSK9 inhibition in LDL cholesterol reduction: genetics and therapeutic
      implications of very low plasma lipoprotein levels.
AB  - Atherosclerosis is a complex process involving the build-up of arterial plaque
      incorporating low-density lipoprotein cholesterol (LDL-C) and an inflammatory
      response. Lowering plasma LDL-C confers cardiovascular benefit for patients with
      hypercholesterolemia resulting from genetic and/or lifestyle factors. Proprotein
      convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of LDL-C
      metabolism. Secreted from liver cells, circulating PCSK9 binds to the LDL
      receptor and is subsequently internalized with the receptor, thereby promoting
      its cellular degradation. As a result, PCSK9 gain-of-function mutations are
      causatively associated with familial hypercholesterolemia, whereas PCSK9 loss-of
      function mutations are associated with very low LDL-C levels and a reduced
      cardiovascular risk. Preventing PCSK9-mediated LDL receptor degradation with
      monoclonal antibodies is a novel strategy to further lower LDL-C, especially in
      patients with severe forms of hypercholesterolemia with elevated LDL-C despite
      maximal conventional treatment and/or in those intolerant to conventional
      therapies. Here, the safety and efficacy of these novel therapeutic agents
      targeting PCSK9 will be discussed with respect to recent clinical trials
      targeting this molecule, as well as inherited hypolipidemias and animal models
      that confer very low LDL-C because of PCSK9 deficiency. 

PMID- 25046269
TI  - Live cell imaging of interactions between replicase and capsid protein of Brome
      mosaic virus using Bimolecular Fluorescence Complementation: implications for
      replication and genome packaging.
AB  - In Brome mosaic virus, it was hypothesized that a physical interaction between
      viral replicase and capsid protein (CP) is obligatory to confer genome packaging
      specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent
      Complementation (BiFC) as a tool for evaluating protein-protein interactions in
      living cells. The efficacy of BiFC was validated by a known interaction between
      replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER)
      site of viral replication. Additionally, co-expression in planta of a bona fide
      pair of interacting protein partners of p1a and p2a had resulted in the assembly
      of a functional replicase. Subsequent BiFC assays in conjunction with mCherry
      labeled ER as a fluorescent cellular marker revealed that CP physically interacts
      with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic
      phase of the ER. The significance of the CP:p2a interaction in BMV replication
      and genome packaging is discussed. 

PMID- 25046270
TI  - Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial
      cells.
AB  - Recently, the product of equine herpesvirus type 1 (EHV-1) ORF1, a homolog to HSV
      1 pUL56, was shown to modulate MHC-I expression and innate immunity. Here, we
      investigated modulation of respiratory epithelial immunity by EHV-1 pUL56 and
      compared responses to those of PBMCs, which are important target cells that allow
      cell-associated EHV-1 viremia. The salient observations are as follows: (i) EHV-1
      significantly down-modulated MHC-I and MHC-II expression in equine respiratory
      epithelial cells (ERECs). MHC-I expression remained unaffected in PBMCs and MHC
      II expression was increased. (ii) Infection with an EHV-1 ORF1 deletion mutant
      partially restored MHC-I and MHC-II expression and altered IFN-alpha and IL-10
      mRNA expression. (iii) Deletion of EHV-1 ORF1 also significantly increased
      chemokine expression and chemotaxis of monocytes and neutrophils in ERECs.
      Collectively, these results suggest a role for EHV-1 pUL56 in modulation of
      antigen presentation, cytokine expression and chemotaxis at the respiratory
      epithelium, but not in PBMC. 

PMID- 25046271
TI  - Bacterial adhesion to poly-(D,L)lactic acid blended with vitamin E: toward gentle
      anti-infective biomaterials.
AB  - Anti-infective properties of biomedical materials are often achieved by loading
      or coating them with powerful bactericides. Undesirably, these bioactive
      molecules can damage the host cells at the biomaterial-tissues interface and,
      sometimes, even determine systemic toxic effects. The search for biomaterials
      able to actively resist infection while displaying a safe cytocompatibility
      profile toward eukaryotic cells is being progressively developed. Poly
      (D,L)lactic acid (PLA) is a broadly used resorbable material with established
      biocompatibility properties. The dissolving surfaces of a biodegradable material
      tend to be per se elusive for bacteria. Here, films of pristine PLA, of PLA
      blended with vitamin E (VitE) and PLA blended with vitamin E acetate (VitE ac)
      were challenged in vitro with the biofilm-producers Staphylococcus epidermidis
      RP62A and Staphylococcus aureus ATCC25923. The bacterial adhesion properties of
      the different materials were investigated on small film disc specimens by a
      method based on microtiter plates. Adherent bacteria were quantified by both CFU
      plating and bioluminescence. Significant decrease in bacterial adhesion and
      biofilm accumulation was found on the surface of both the enriched polymers.
      These findings, together with the favorable intrinsic properties of PLA and the
      desirable bioactivities conferred by VitE, point up the VitE-blended PLA polymers
      as gentle anti-infective biomaterials.

PMID- 25046273
TI  - In-home antibiotic storage among Australian Chinese migrants.
AB  - OBJECTIVES: To estimate the prevalence of in-home antibiotic storage among
      Australian Chinese migrants and to identify the risk factors associated with
      storing antibiotics at home. METHODS: Four hundred and sixty-nine Chinese
      migrants in Australia who were recruited through Chinese social websites
      completed an online questionnaire about antibiotic use. Logistic regression
      analysis was conducted to assess the associations between possible risk factors
      and storing antibiotics at home. RESULTS: According to the web-based survey, 220
      (47%) out of 469 participants reported having antibiotics stored at home.
      Previous use of antibiotics, bringing antibiotics in from outside Australia, and
      a pro-attitude to the use of leftover antibiotics were significantly associated
      with storing antibiotics at home after adjusting for age, gender, and household
      annual income. Participants who self-reported an awareness of antibiotic side
      effects or resistance had a slightly higher but not significant risk of storing
      antibiotics at home. CONCLUSIONS: Approximately half of the participants in this
      study had antibiotics stored at home. The risk of using the antibiotics stored at
      home without medical consultation is of concern. Education programs need to
      target those with high-risk behaviours to curtail the inappropriate practice of
      antibiotic use and storage among Australian Chinese migrants.

PMID- 25046272
TI  - Peripheral opioid receptor blockade increases postoperative morphine demands--a
      randomized, double-blind, placebo-controlled trial.
AB  - Experimental studies suggest that a large proportion of opioid analgesia can be
      mediated by peripheral opioid receptors. This trial examined the contribution of
      such receptors to clinical analgesia induced by intravenous morphine. We
      hypothesized that the selective blockade of peripheral opioid receptors by
      methylnaltrexone (MNX) would increase the patients' demand for morphine to
      achieve satisfactory postoperative pain relief. In a double-blind, placebo
      controlled, sequential 2-center trial, 50 patients undergoing knee replacement
      surgery were randomized (1:1) to receive either subcutaneous MNX (0.9 mg/kg)
      (hospital I: n=14; hospital II: n=11) or saline (hospital I: n=13; hospital II:
      n=12) at the end of surgery. The primary endpoint was the cumulative amount of
      intravenous morphine administered during the first 8 hours. Secondary endpoints
      were pain scores at rest and during movement (by numerical rating scale and
      McGill Questionnaire), vital signs, adverse side effects, and withdrawal
      symptoms. After MNX, demands for morphine were strongly (by about 40%) increased
      (hospital I: 35.31 +/- 12.99 mg vs 25.51 +/- 7.92 mg, P=0.03; hospital II: 35.42
      +/- 11.73 mg vs 24.80 +/- 7.84 mg, P=0.02; pooled data: P<.001; means +/- SD).
      Secondary endpoints were similar in all groups (P>.05). Thus, a significant
      proportion of analgesia produced by systemically administered morphine is
      mediated by peripheral opioid receptors. Drugs that selectively activate such
      receptors should have the potential to produce powerful clinical pain relief.

PMID- 25046274
TI  - HIV testing among financially disadvantaged women diagnosed with cervical cancer.

PMID- 25046276
TI  - Evolution of mammalian and avian bornaviruses.
AB  - Recently, Avian Bornavirus (ABV) was identified to be a new member of the
      Bornaviridae family consisting solely of the mammal-infecting Borna disease virus
      (BDV). Here, to gain more insights into the evolution of these bornaviruses, the
      time-stamped N gene sequences of BDV genotype 1 (BDV1) and ABV were subjected to
      Bayesian coalescent analyses. The nucleotide substitution rates and the
      divergence times were estimated. Age calculations suggested that the first
      diversification event of the analyzed BDV1 isolates might have taken place about
      300years ago, and revealed that ABV was an old virus newly recognized. Great
      differences were observed in the rate of nucleotide substitution and the pattern
      of codon usage bias between BDV1 and ABV. Moreover, the analyzed bornaviruses
      might be descended from an AT-rich ancestor. 

PMID- 25046275
TI  - Neural responses from the filiform receptor neuron afferents of the wind
      sensitive cercal system in three cockroach species.
AB  - The wind-sensitive insect cercal system is involved in many important behaviors,
      such as initiating terrestrial escape responses and providing sensory feedback
      during flight. The occurrence of these behaviors vary in cockroach species
      Periplaneta americana (strong terrestrial response and flight), Blaberus
      craniifer (weak terrestrial response and flight), and Gromphodorhina portentosa
      (no terrestrial response and no flight). A previous study focusing on wind
      sensitive interneuron (WSI) responses demonstrated that variations in sensory
      processing of wind information accompany these behavioral differences. In this
      study, we recorded extracellularly from the cercal nerve to characterize filiform
      afferent population responses to different wind velocities to investigate how
      sensory processing differs across these species at the initial encoding of wind.
      We compared these results and responses from the WSI population to examine
      information transfer at the first synapse. Our main results were: (1) G.
      portentosa had the weakest responses of the three species over the stimulus
      duration and possessed the smallest cerci with the least filiform hair receptors
      of the three species; (2) B. craniifer filiform responses were similar to or
      greater than P. americana responses even though B. craniifer possessed smaller
      cerci with less filiform hair receptors than P. americana; (3) the greater
      filiform afferent responses in B. craniifer, including a larger amplitude second
      positive peak compared to the other two species, suggest more synchronous
      activity between filiform afferents in this species; (4) the transfer of
      information at the first synapse appears to be similar in both P. americana and
      G. portentosa, but different in B. craniifer. 

PMID- 25046277
TI  - Effect of a chronic treatment with an mGlu5 receptor antagonist on brain
      serotonin markers in parkinsonian monkeys.
AB  - In Parkinson's disease (PD) and l-3,4-dihydroxyphenylalanine (L-DOPA)-induced
      dyskinesias (LIDs), overactivity of brain glutamate neurotransmission is
      documented and antiglutamatergic drugs decrease LID. Serotonin (5-HT) receptors
      and transporter (SERT) are also implicated in LID and we hypothesize that
      antiglutamatergic drugs can also regulate brain serotoninergic activity. Our aim
      was to investigate the long-term effect of the prototypal metabotropic glutamate
      5 (mGlu5) receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) with L
      DOPA on basal ganglia SERT, 5-HT(1A) and 5-HT(2A) receptor levels in monkeys
      lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP monkeys
      were treated for one month with L-DOPA and developed LID while those treated with
      L-DOPA and MPEP (10 mg/kg) developed significantly less LID. Normal controls and
      saline-treated MPTP monkeys were included for biochemical analysis. The MPTP
      lesion and experimental treatments left unchanged striatal 5-HT concentrations.
      MPTP lesion induced an increase of striatal 5-HIAA concentrations similar in all
      MPTP monkeys as compared to controls. [(3)H]-8-OH-DPAT and [(3)H]-citalopram
      specific binding levels to 5-HT(1A) receptors and SERT respectively remained
      unchanged in the striatum and globus pallidus of all MPTP monkeys compared to
      controls and no difference was observed between groups of MPTP monkeys. [(3)H]
      ketanserin specific binding to striatal and pallidal 5-HT2A receptors was
      increased in L-DOPA-treated MPTP monkeys as compared to controls, saline and L
      DOPA+MPEP MPTP monkeys and no difference between the latter groups was observed;
      dyskinesia scores correlated positively with this binding. In conclusion,
      reduction of development of LID with MPEP was associated with lower striatal and
      pallidal 5-HT2A receptors showing that glutamate activity also affects
      serotoninergic markers.

PMID- 25046278
TI  - High-throughput image analysis of tumor spheroids: a user-friendly software
      application to measure the size of spheroids automatically and accurately.
AB  - The increasing number of applications of three-dimensional (3D) tumor spheroids
      as an in vitro model for drug discovery requires their adaptation to large-scale
      screening formats in every step of a drug screen, including large-scale image
      analysis. Currently there is no ready-to-use and free image analysis software to
      meet this large-scale format. Most existing methods involve manually drawing the
      length and width of the imaged 3D spheroids, which is a tedious and time
      consuming process. This study presents a high-throughput image analysis software
      application - SpheroidSizer, which measures the major and minor axial length of
      the imaged 3D tumor spheroids automatically and accurately; calculates the volume
      of each individual 3D tumor spheroid; then outputs the results in two different
      forms in spreadsheets for easy manipulations in the subsequent data analysis. The
      main advantage of this software is its powerful image analysis application that
      is adapted for large numbers of images. It provides high-throughput computation
      and quality-control workflow. The estimated time to process 1,000 images is about
      15 min on a minimally configured laptop, or around 1 min on a multi-core
      performance workstation. The graphical user interface (GUI) is also designed for
      easy quality control, and users can manually override the computer results. The
      key method used in this software is adapted from the active contour algorithm,
      also known as Snakes, which is especially suitable for images with uneven
      illumination and noisy background that often plagues automated imaging processing
      in high-throughput screens. The complimentary "Manual Initialize" and "Hand Draw"
      tools provide the flexibility to SpheroidSizer in dealing with various types of
      spheroids and diverse quality images. This high-throughput image analysis
      software remarkably reduces labor and speeds up the analysis process.
      Implementing this software is beneficial for 3D tumor spheroids to become a
      routine in vitro model for drug screens in industry and academia. 

PMID- 25046279
TI  - The application of impulse oscillation system for the evaluation of treatment
      effects in patients with COPD.
AB  - There are only a few reports of the use of impulse oscillation system (IOS) for
      the evaluation of COPD treatment. In this study, we applied IOS and spirometry to
      evaluate the effectiveness of fluticasone propionate and salmeterol (SFC)
      combined with tiotropium (TIO) in COPD patients. Following a 4-week run-in period
      with TIO (18 MUg once daily) treatment, COPD patients were randomized to SFC
      (250/50 MUg twice daily; SFC+TIO group, n=25), or TIO alone (TIO group, n=31).
      Pulmonary functions were recorded by IOS and spirometry before and after the
      study period. The SFC+TIO group showed significant improvements in inspiratory
      resistance at 5 Hz and resonant frequency, as well as in FVC and FEV1, after the
      12-week treatment (p<0.05). Since there were no significant correlations between
      improvements in IOS measurements and FVC or FEV1, IOS may provide a physiological
      point of view that is different from spirometry and seemed to be applicable as an
      additional assessment tool targeting COPD patients.

PMID- 25046280
TI  - The potential for health-related uses of mobile phones and internet with homeless
      veterans: results from a multisite survey.
AB  - BACKGROUND: Addressing the health needs of homeless veterans is a priority in the
      United States, and, although information technologies can potentially improve
      access to and engagement in care, little is known about this population's use of
      information technologies or their willingness to use technologies to communicate
      with healthcare providers and systems. MATERIALS AND METHODS: This study fills
      this gap through a survey of homeless veterans' use of information technologies
      and their attitudes about using these technologies to assist with accessing
      needed healthcare services. RESULTS: Among the 106 homeless veterans surveyed,
      89% had a mobile phone (one-third were smartphones), and 76% used the Internet.
      Among those with a mobile phone, 71% used text messaging. Nearly all respondents
      (93%) were interested in receiving mobile phone reminders (text message or phone
      call) about upcoming medical appointments, and a similar proportion (88%) wanted
      mobile phone outreach asking if they would like to schedule an appointment if
      they had not been seen by a health provider in over a year. In addition,
      respondents already used these technologies for information and communication
      related to health, housing, and jobs. CONCLUSIONS: These findings suggest new
      avenues for communication and health interventions for hard-to-reach homeless
      veterans.

PMID- 25046281
TI  - The association baseline NIH Stroke Scale score with ABO blood-subtypes in young
      patients with acute ischemic stroke.
AB  - OBJECTIVES: The presence of the A and B blood group antigens has been associated
      with risk of arterial thrombosis. The aim of the current study was to design a
      new simpler form of National Institutes of Health Stroke Scale (NIHSS) for use on
      admission, and assess the association of blood groups with NIHSS score in young
      stroke patients. METHODS: We conducted this study in 1311 young Chinese adults
      with acute ischemic cerebral stroke. The outcome measures included a composite
      favorable outcome (defined as a modified Rankin Scale (mRS) of 0 or 2) and poor
      outcome (defined as a modified Rankin Scale score of 3 or 6) at discharge; a
      minor strokes (NIHSS scores 0-5) and severe strokes (NIHSS scores >=6). Logistic
      regression analyses were used to determine the association between ABO blood
      groups and stroke severity. RESULTS: Regression analysis confirmed in relative to
      patients with AB subtype, Oxfordshire community stroke project classification
      (OCSP) subtype and serum white blood cell (WBC) were the major predictors for
      stroke severity. Meanwhile, diabetes, serum triglyceride and uric acid levels
      were determined as independent indicators of stroke severity in A, B and O blood
      subtype respectively. The optimal cutoff score of the baseline NIHSS was <=5 for
      patients with non-O subtype, the optimal cutoff score of the baseline NIHSS was
      <=7 for patients with blood O subtype. CONCLUSIONS: Our analysis provide
      compelling information regarding the ABO blood groups differences in predictors
      of stroke severity and the different validity of NIHSS scores in predicting
      prognosis at discharge between O subtype and non-O subtype.

PMID- 25046282
TI  - Increased augmentation index is paradoxically associated with lower in-hospital
      mortality in patients with acute ischemic stroke.
AB  - OBJECTIVE: To evaluate the association between arterial stiffness and stroke
      severity and in-hospital outcome in patients admitted with acute ischemic stroke.
      METHODS: We prospectively studied 415 consecutive patients who were admitted with
      acute ischemic stroke (39.5% males, age 78.8 +/- 6.6 years). On the third day of
      hospitalization, the following markers of arterial stiffness were recorded:
      central systolic blood pressure (cSBP), diastolic BP (cDBP), mean pressure (cMP),
      pulse pressure (cPP), augmentation index (AIx) and pulse wave velocity (PWV). The
      severity of stroke was assessed on admission with the National Institutes of
      Health Stroke Scale (NIHSS) score. The outcome was evaluated with rates of
      dependency at discharge (modified Rankin scale score between 2 and 5) and in
      hospital mortality. RESULTS: None of the markers of arterial stiffness showed
      significant correlation with the NIHSS score on admission. However, there was a
      trend for an inverse correlation with AIx (r = -0.142, p = 0.064) and for a
      positive correlation with PWV (r = 0.235, p = 0.054). None of the markers of
      arterial stiffness differed between patients who were dependent at discharge and
      those who were independent. Patients who died during hospitalization had higher
      cDBP and cMP but lower cPP and AIx than patients who were discharged. In binary
      logistic regression analysis, independent predictors of in-hospital mortality
      were NIHSS score on admission (relative risk (RR) 1.16, 95% confidence interval
      (CI) 1.08-1.25, p < 0.001), presence of atrial fibrillation (RR 6.41, 95% CI 1.37
      29.93, p = 0.018) and AIx (RR 0.94, 95% CI 0.89-0.99, p = 0.030). CONCLUSIONS:
      Increased AIx appears to be associated with lower in-hospital mortality rates in
      elderly patients with acute ischemic stroke. Other markers of arterial stiffness
      do not appear to be associated with short-term outcome in this population.

PMID- 25046283
TI  - Dissection of the cord blood stromal component reveals predictive parameters for
      culture outcome.
AB  - In regenerative medicine, human cord blood-derived multipotent mesenchymal
      stromal cells (CBMSCs) stand out for their biological peculiarities demonstrated
      in in vitro and in vivo preclinical studies. Here, we present our 9-year
      experience for the consistent isolation of CBMSCs. Although nearly one CB unit
      out of two retains the potential to give rise to MSC colonies, only 46% of them
      can be cultured till low passages (P>=4), but one-fourth of those reaches even
      higher passages (P>=8). Subsequent characterization for morphological, clonal,
      differentiation, and proliferation properties revealed two divergent CBMSC
      behaviors. In particular, a cumulative population doublings cut-off (CPD=15) was
      identified that undoubtedly distinguishes two growth curves, and different
      degrees of commitment toward osteogenesis were observed. These data clearly show
      the existence of at least two distinct CBMSC subsets: one mainly short-living and
      less proliferative (SL-CBMSCs), the other long-living, with higher growth rate,
      and, very importantly, with significantly (P<=0.01) longer telomere (LL-CBMSCs).
      Moreover, significant differences in the immunoprofile before seeding were found
      among CB units giving rise to LL-CBMSCs or SL-CBMSCs or showing no colony
      formation. Finally, all the aforementioned results provided a peculiar and useful
      set of parameters potentially predictive for CBMSC culture outcome. 

PMID- 25046284
TI  - AJOB 2.0: Taking bioethics to a new level.

PMID- 25046285
TI  - Whither brain death?
AB  - The publicity surrounding the recent McMath and Munoz cases has rekindled public
      interest in brain death: the familiar term for human death determination by
      showing the irreversible cessation of clinical brain functions. The concept of
      brain death was developed decades ago to permit withdrawal of therapy in hopeless
      cases and to permit organ donation. It has become widely established medical
      practice, and laws permit it in all U.S. jurisdictions. Brain death has a
      biophilosophical justification as a standard for determining human death but
      remains poorly understood by the public and by health professionals. The current
      controversies over brain death are largely restricted to the academy, but some
      practitioners express ambivalence over whether brain death is equivalent to human
      death. Brain death remains an accepted and sound concept, but more work is
      necessary to establish its biophilosophical justification and to educate health
      professionals and the public. 

PMID- 25046286
TI  - Changing the conversation about brain death.
AB  - We seek to change the conversation about brain death by highlighting the
      distinction between brain death as a biological concept versus brain death as a
      legal status. The fact that brain death does not cohere with any biologically
      plausible definition of death has been known for decades. Nevertheless, this fact
      has not threatened the acceptance of brain death as a legal status that permits
      individuals to be treated as if they are dead. The similarities between "legally
      dead" and "legally blind" demonstrate how we may legitimately choose bright-line
      legal definitions that do not cohere with biological reality. Not only does this
      distinction bring conceptual coherence to the conversation about brain death, but
      it has practical implications as well. Once brain death is recognized as a social
      construction not grounded in biological reality, we create the possibility of
      changing the social construction in ways that may better serve both organ donors
      and recipients alike. 

PMID- 25046287
TI  - Brain-dead and pregnant in Texas.
AB  - When a Texas hospital continued ventilator support for a pregnant patient who met
      the neurological criteria for the determination of death, it acted against the
      wishes of the patient's husband and other family members. The hospital stated
      that its treatment decision was required under the Texas Advance Directives Act,
      in particular the "pregnancy exclusion" that instructs providers to continue life
      sustaining treatment as long as the patient is pregnant, notwithstanding contrary
      instructions in the patient's living will or from the patient's surrogate
      decision-maker. Contrary to the hospital's stated position, however, neither the
      literal words of the pregnancy exclusion nor the Advance Directives Act read as a
      whole requires continued ventilator support once a pregnant patient is determined
      to be brain dead. 

PMID- 25046288
TI  - A functionalist view of brain death.

PMID- 25046289
TI  - The paradox of the dead donor rule: increasing death on the waiting list.

PMID- 25046290
TI  - Beyond the essence of death.

PMID- 25046291
TI  - Irreversible shmirreversible.

PMID- 25046292
TI  - Death as a legal fiction.

PMID- 25046293
TI  - Toward a science of brain death.

PMID- 25046294
TI  - Structuring conversations on the fact and fiction of brain death.

PMID- 25046295
TI  - The social construction of death, biological plausibility, and the brain death
      criterion.

PMID- 25046296
TI  - A legal fiction with real consequences.

PMID- 25046297
TI  - Sketching the alternative to brain death: dying through organ donation.

PMID- 25046298
TI  - Brain dead patients are still whole organisms.

PMID- 25046299
TI  - Defining death without science? A pragmatic rebuttal.

PMID- 25046300
TI  - Beyond transplantation: considering brain death as a hard clinical endpoint.

PMID- 25046301
TI  - Constructing the legal concept of death: the counterhegemonic option.

PMID- 25046302
TI  - Death, Hume, emotions, and the essential role of the physician.

PMID- 25046303
TI  - Pregnancy, brain death, and posthumous motherhood: a provisional policy proposal.

PMID- 25046304
TI  - The pregnancy exclusions: respect for women requires repeal.

PMID- 25046305
TI  - Should we scrap the dead donor rule?

PMID- 25046306
TI  - Neuroprotective Effects of Co-UltraPEALut on Secondary Inflammatory Process and
      Autophagy Involved in Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that
      contributes to neuronal damage and behavioral impairment. In the present study,
      we performed a widely used model of TBI to determine the neuroprotective
      propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a
      flavonoid luteolin (Lut), given as a co-ultramicronized compound Co-ultraPEALut.
      We demonstrated that the treatment with Co-ultraPEALut resulted in a significant
      improvement of motor and cognitive recovery after controlled cortical impact, as
      well as markedly reducing lesion volumes. Moreover, our results revealed the
      ability of Co-ultraPEALut to reduce brain trauma through modulation of nuclear
      factor-kappaB activation. In addition, treatment with Co-ultraPEALut
      significantly enhanced the post-TBI expression of the neuroprotective
      neurotrophins glial cell line-derived neurotrophic factor compared with vehicle.
      Co-ultraPEALut at the dose of 1 mg/kg also modulated apoptosis, the release of
      cytokine and reactive oxygen species, the activation of chymase, tryptase, and
      nitrotyrosine, and inhibited autophagy. Thus, our data demonstrated that Co
      ultraPEALut at a lower dose compared with PEA alone can exert neuroprotective
      effects and the combination of both could improve their ability to counteract the
      neurodegeneration and neuroinflammation induced by TBI. 

PMID- 25046307
TI  - Long-term depression at distinct glutamatergic synapses in the basal ganglia.
AB  - Long-term adaptations of synaptic transmission are believed to be the cellular
      basis of information storage in the brain. In particular, long-term depression of
      excitatory neurotransmission has been under intense investigation since
      convergent lines of evidence support a crucial role for this process in learning
      and memory. Within the basal ganglia, a network of subcortical nuclei forming a
      key part of the extrapyramidal motor system, plasticity at excitatory synapses is
      essential to the regulation of motor, cognitive, and reward functions. The
      striatum, the main gateway of the basal ganglia, receives convergent excitatory
      inputs from cortical areas and transmits information to the network output
      structures and is a major site of activity-dependent plasticity. Indeed, long
      term depression at cortico-striatal synapses modulates the transfer of
      information to basal ganglia output structures and affects voluntary movement
      execution. Cortico-striatal plasticity is thus considered as a cellular substrate
      for adaptive motor control. Downstream in this network, the subthalamic nucleus
      and substantia nigra nuclei also receive glutamatergic innervation from the
      cortex and the subthalamic nucleus, respectively. Although these connections have
      been less investigated, recent studies have started to unravel the molecular
      mechanisms that contribute to adjustments in the strength of cortico-subthalamic
      and subthalamo-nigral transmissions, revealing that adaptations at these synapses
      governing the output of the network could also contribute to motor planning and
      execution. Here, we review our current understanding of long-term depression
      mechanisms at basal ganglia glutamatergic synapses and emphasize the common and
      unique plastic features observed at successive levels of the network in healthy
      and pathological conditions.

PMID- 25046308
TI  - Influence of vitamin E and quercetin on Nigerian Bonny Light crude oil-induced
      neuronal and testicular toxicity in Wistar rats.
AB  - BACKGROUND: Mounting experimental evidence highlights the testicular and neuronal
      toxicity of environmental/industrial chemicals in experimental animals via the
      mechanism involving oxidative damage. Nigerian Bonny Light crude oil (BLCO) has
      been reported to exhibit reproductive and neuronal toxicity in male rats. Studies
      have shown that vitamin E and quercetin protect rat neuronal and testicular cells
      from environmental chemical-induced oxidative damage. We investigated the
      possible protective role of quercetin and vitamin E in BLCO induced-neuronal and
      testicular toxicity. METHODS: Male rats were administered BLCO at doses of 400
      and 800 mg/kg body wt/day p.o. three times/week for 6 weeks. Other groups were co
      administered BLCO (400 and 800 mg/kg body wt/day p.o.) with/without vitamin E (50
      mg/kg body wt/day p.o.) or quercetin (10 mg/kg body wt/day p.o.) three times/week
      for 6 weeks, respectively. RESULTS: Semen quality deteriorated, testosterone and
      luteinizing hormone (LH) levels were significantly decreased, and follicle
      stimulating hormone (FSH) increased following BLCO reatment. There was a
      significant decline in the activities of superoxide dismutase (SOD), catalase
      (CAT), reduced glutathione (GSH), and glutathione-S-transferase (GST) with
      concomitant increased levels of lipid peroxidation and activities of xanthine
      oxidase (XO) in a dose-dependent manner, in testes and brain of rats. Co
      administration with vitamin E or quercetin reversed BLCO-induced neuronal and
      testicular toxicity by preventing oxidative stress, improving sperm quality, and
      restoring hormonal levels relative to controls. CONCLUSIONS: BLCO altered
      reproductive indices and induced neuronal toxicity via the mechanism of oxidative
      stress. Quercetin and vitamin E showed possible chemoprotection against the
      toxicity.

PMID- 25046309
TI  - Analgesic, anti-inflammatory, and anti-oxidant  activities of Phlogacanthus
      thyrsiflorus leaves.
AB  - BACKGROUND: Our present study was carried out to explore the potential role of
      the methanol extract from the leavesof Phlogocanthus thyrsiflorus (PT) Nees. in
      central and peripheral analgesic activities using hot plate and acetic acid
      induced writhing methods. We also tested the antiinflammatory effects and anti
      oxidant activity using carrageenan-induced paw edema and the DPPH method,
      respectively. METHODS: Methanol extracts of PT leaves were prepared using 500 g
      powder in 1.8 L methanol by percolation method, followed by evaporation in a
      rotary evaporator under controlled temperature and pressure. The crude methanol
      extract was dried by freeze drier and preserved at 4  degrees C. RESULTS: Oral
      administration of PT significantly (p < 0.05)increased the reaction time at
      55.73% (250 mg/kg) and 72.81% (500 mg/kg) inhibition (p < 0.05) in the hot plate
      test at 3 h. PT significantly (p < 0.05) inhibited 42.17% (250 mg/kg) and 56.63%
      (500 mg/kg) acetic acid-induced writhing. PT leaves (250 and 500 mg/kg) also
      significantly (p < 0.05) inhibited paw edema 6 h after carrageenan injection.
      Furthermore, this plant showed significant (p < 0.05) free radical-scavenging
      activity at a dose range of 25-800 MUg/mL. CONCLUSIONS: Based on the findings, we
      can conclude that PT leaf possesses analgesic, anti-inflammatory, and antioxidant
      activities. Preliminary phytochemical study of PT leaves revealed the presence of
      flavonoids, tannins and triterpens in methanol extract which could be correlated
      with its observed biological activities.

PMID- 25046310
TI  - L-carnitine is a calcium chelator: a reason for its  useful and toxic effects in
      biological systems.
AB  - BACKGROUND: Investigation of the direct link between l-carnitine (LC), a
      quaternary ammonium compound that facilitates the passage of unsaturated fatty
      acids into the mitochondrial matrix, and free calcium (Ca2+) is needed to explain
      a number of varying results obtained from different in vitro and in vivo studies
      of LC as a supplement. METHODS: The chemical structure of LC, which contains
      oxygen ligand atoms, prompted to measure its activity asa Ca2+ chelator. The
      measurement was carried out spectrophotometri cally by measuring the reduction in
      the formation of Ca2+-o-cresolphthalein complexone (Ca-CPC) in the presence of
      different doses of LC (0.075, 0.75, and 7.5 mM) compared to the control (0.0 mM
      LC). RESULTS: The effect of LC was measured as a free entity in solution and when
      added to human serum. Our results showed a significant decrease (p < 0.05) in the
      average absorbance of Ca-CPC in the presence of LC compared to the control.
      CONCLUSIONS: In conclusion, LC exhibits a significant Ca2+ chelating activity. As
      Ca2+ is vital in the biochemical and physiological processes of living cells, LC
      could be affecting the calcium-dependent biological systems by limiting the
      levels of free Ca2+. Examples include decelerating the blood clotting process,
      amplifying the effect of anticoagulants, reducing nitric oxide synthase activity,
      inhibiting

PMID- 25046311
TI  - Cell cycle checkpoints and pathogenesis of HIV-1  infection: a brief overview.
AB  - To understand HIV pathogenesis or development is no simple undertaking and
      neither is the cell cycle which is highly complex that requires the coordination
      of multiple events and machinery. It is interesting that these two processes are
      interrelated, intersect and interact as HIV-1 infection results in cell cycle
      arrest at the G2 phase which is accompanied by massive CD4+ T cell death. For its
      own benefit, in an impressive manner and with the overabundance of tactics, HIV
      maneuvers DNA damage responses and cell cycle check points for viral replication
      at different stages from infection, to latency and to pathogenesis. Although the
      cell cycle is the most critical aspect involved in both viral and cellular
      replication, in this review, our main focus is on recent developments, including
      our own observations in the field of cell cycle proteins, checkpoints and
      strategies utilized by the viruses to manipulate these pathways to promote their
      own replication and survival. We will also discuss the emerging concept of
      targeting the replication initiation machinery for HIV therapy.

PMID- 25046312
TI  - Rapid adaptation to time-compressed speech   in young and older adults.
AB  - BACKGROUND: The ability of human listeners to comprehend rapid speech improves
      quickly with experience, a process known as adaptation. Whether inefficient
      adaptation to rapid speech partially accounts for the marked difficulties of
      older listeners with rapid speech is not clear. METHODS: Two conditions of
      adaptation to time-compressed speech were used. A baseline condition intended to
      test the hypothesis that adaptation is different in older and younger listeners,
      and an interference condition in which sentences compressed to two different
      rates were interleaved. Identification accuracy was compared between two time
      points (before and after adaptation) and between older and younger listeners.
      RESULTS: The effects of adaptation did not differ between younger and older
      listeners in either adaptation condition. CONCLUSIONS: It seems that once initial
      performance differences are taken into account, rapid adaptation to time
      compressed speech is as effective and as immune to interference by competing
      speech rates in younger and older adults.

PMID- 25046313
TI  - The mechanism of direct stimulation of the   cochlea by vibrating the round
      window.
AB  - BACKGROUND: Active middle ear implants such as the vibrant sound bridge (VSB)
      have been placed on the round window (RW) in patients with conductive or mixed
      hearing loss, with satisfactory hearing results. Several observations show that
      the mechanism of RW stimulation is not completely understood. The purpose of the
      present study was to compare different coupling procedures between the transducer
      and the RW in order to contribute to an understanding of the mechanism of RW
      stimulation. METHODS: Five fat sand rats underwent ablation of the left ear and
      opening of the right bulla, followed by baseline measurements of thresholds of
      auditory nerve brainstem evoked responses (ABR) to air and bone conduction click
      stimuli. Subsequently the malleus and incus were removed from the right middle
      ear, modeling a conductive hearing loss in which the VSB on the RW is indicated.
      In the next stage of the experiment, a rod attached to the bone vibrator was
      placed gently on the RW membrane and then on saline fluid applied to the RW
      niche. ABR thresholds were recorded following both placements. RESULTS: Mean
      baseline ABR threshold in response to air conduction stimuli was 48 +/- 4 dB;
      mean ABR threshold when the rod was placed on the dry RW membrane was 99 +/- 12
      dB; mean ABR threshold when the rod was in the saline on RW niche was 79 +/- 7
      dB. CONCLUSIONS: ABR thresholds were better (lower) with stimulation of fluid on
      the RW membrane compared to direct stimulation of the RW, providing further
      evidence of a direct fluid pathway.

PMID- 25046314
TI  - Auditory-evoked cortical activity: contribution of   brain noise, phase locking,
      and spectral power.
AB  - BACKGROUND: The N1-P2 is an obligatory cortical response that can reflect the
      representation of spectral and temporal characteristics of an auditory stimulus.
      Traditionally,mean amplitudes and latencies of the prominent peaks in the
      averaged response are compared across experimental conditions. Analyses of the
      peaks in the averaged response only reflect a subset of the data contained within
      the electroencephalogram(EEG) signal. We used single-trial analyses techniques to
      identify the contribution of brain noise,neural synchrony, and spectral power to
      the generation of P2 amplitude and how these variables may change across age
      group. This information is important for appropriate interpretation of event
      related potentials (ERPs) results and in understanding of age-related neural
      pathologies. METHODS: EEG was measured from 25 younger and 25 older normal
      hearing adults. Age-related and individual differences in P2 response amplitudes,
      and variability in brain noise, phase locking value (PLV), and spectral power (4
      8 Hz) were assessed from electrode FCz. Model testing and linear regression were
      used to determine the extent to which brain noise, PLV, and spectral power
      uniquely predicted P2 amplitudes and varied by age group. RESULTS: Younger adults
      had significantly larger P2 amplitudes, PLV, and power compared to older adults.
      Brain noise did not differ between age groups. The results of regression testing
      revealed that brain noise and PLV, but not spectral power were unique predictors
      of P2 amplitudes. Model fit was significantly better in younger than in older
      adults. CONCLUSIONS: ERP analyses are intended to provide a better understanding
      of the underlying neural mechanisms that contribute to individual and group
      differences in behavior. The current results support that age-related declines in
      neural synchrony contribute to smaller P2 amplitudes in older normal hearing
      adults. Based on our results, we discuss potential models in which differences in
      neural synchrony and brain noise can account for associations with P2 amplitudes
      and behavior and potentially provide a better explanation of the neural
      mechanisms that underlie declines in auditory processing and training benefits.

PMID- 25046315
TI  - Antiplasmodial potential of homeopathic drugs Chelidonium and nosode against
      Plasmodium berghei infection.
AB  - BACKGROUND: Malaria remains a major global health concern in developing regions
      of the world. Homeopathy, a holistic system of medicine, has a lot to offer in
      protecting against malaria. METHODS: In the present study, antimalarial efficacy
      of combination of two homeopathic drugs Chelidonium 30 and nosode 30 has been
      evaluated in vivo against Plasmodium berghei (P. berghei) infection using Peters
      4-day test. Biochemical assays have been performed to assess the levels of
      hepatic and renal function biomarkers upon drug treatment using diagnostic kits.
      RESULTS: The combination of the drugs demonstrated considerable in vivo
      antimalarial activity with chemosuppression of 91.45% on day 7. The combination
      also significantly (p < 0.0005) enhanced the mean survival time of mice which was
      calculated to be 22.5 +/- 6.31 days, whereas it was 8.55 +/- 0.83 days in
      infected control. The increase in levels of the liver function marker enzymes
      tested in serum of treated mice were significantly less (p < 0.0005) than those
      observed in infected control on day 10. The serum urea and creatinine used for
      assessment of renal sufficiency were slightly elevated above normal, but were
      statistically significant (p < 0.0005) as compared to infected control.
      CONCLUSIONS: The study establishes the effectiveness of the combination against
      P. berghei in vivo along with the safety of the drugs to the liver and kidney
      functions of the host.

PMID- 25046316
TI  - Photothermal inhibition of neural activity with near-infrared-sensitive
      nanotransducers.
AB  - A neural stimulation technique that can inhibit neural activity reversibly and
      directly without genetic modification is valuable for understating complex brain
      functions and treating brain diseases. Here, we propose a near-infrared (NIR)
      activatable nanoplasmonic technique that can inhibit the electrical activity of
      neurons by utilizing gold nanorods (GNRs) as photothermal transducers on cellular
      membranes. The GNRs were bound onto the plasma membrane of neurons and irradiated
      with NIR light to induce GNR-mediated photothermal heating near the membrane. The
      electrical activity from the cultured neuronal networks pretreated with GNRs was
      immediately inhibited upon NIR irradiation, and fully restored when NIR light was
      removed. The degree of inhibition could be precisely modulated by tuning the
      laser intensity, thereby enabling restoration of firing of a hyperactive neuronal
      network with epileptiform activity. This nanotechnological approach to inhibit
      neural activity provides a powerful therapeutic platform to control cellular
      functions associated with disordered neural circuits.

PMID- 25046317
TI  - The prevalence and characteristics associated with excessive daytime sleepiness
      among Australian workers.
AB  - OBJECTIVE: To estimate the prevalence of excessive daytime sleepiness (EDS) and
      its associated factors in a mixed population of employed Australian workers.
      METHODS: Study participants (n = 707) were volunteers from various Melbourne
      workplaces, participating in a workplace physical activity program in 2008.
      Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS), with
      EDS defined as ESS scores >10. RESULTS: In this population of adult employees
      (40.0% male; mean age 40.2 +/- 10.4 years), prevalence of EDS was 16.0%.
      Characteristics associated with EDS and higher ESS scores were age, higher body
      mass index, markers of poorer diet, and markers of poorer mental health.
      CONCLUSIONS: Excessive daytime sleepiness is potentially an important contributor
      to lower productivity and poorer mental health in the workplace. Our finding
      suggests that workplace health programs aimed at improving diet and body weight
      may also help alleviate EDS.

PMID- 25046318
TI  - Exhaled breath condensate pH and FeNO as biomarkers of acute and chronic exposure
      to hazards at swine farms.
AB  - OBJECTIVE: The noninvasive biomarkers of respiratory impairment were assessed in
      15 swine confinement (SC) workers and 9 respiratory healthy, nonsmoking
      volunteers (HV). METHODS: Spirometry, fraction of exhaled nitric oxide (FeNO),
      and exhaled breath condensate (EBC) pH were assessed in SC workers after one
      working shift and one working week and in HV after 5-hour exposure in SC.
      RESULTS: Half of the respiratory symptoms (in 8 of 15 SC workers) were work
      related. Basal FeNO values were 7.5 ppb higher in the SC workers compared with
      HV. In the SC workers, EBC pH increased for 0.17 at the end of a working week (P
      < 0.001). In HV, 5-hour exposure in SC induced 8% drop in forced expiratory flow
      at 25% of the pulmonary volume (FEF25) (P = 0.008), EBC pH drop for 0.10 units (P
      = 0.003), and FeNO drop by 1.8 ppb (P = 0.047). CONCLUSIONS: EBC pH was suggested
      as a biomarker of acute airway acidification in HV, whereas the SC workers showed
      signs of the "healthy worker effect."

PMID- 25046319
TI  - Hidden costs associated with venous thromboembolism: impact of lost productivity
      on employers and employees.
AB  - OBJECTIVE: To determine productivity loss and indirect costs with deep vein
      thrombosis (DVT) and pulmonary embolism (PE). METHODS: Medical and pharmacy
      claims with short-term disability (STD) and long-term disability (LTD) claims
      from 2007 to 2010 were analyzed from the Integrated Benefits Institute's Health
      and Productivity Benchmarking (IBI-HPB) database (STD and LTD claims) and IMS
      LifeLinkTM data (medical and pharmacy claims), which were indirectly linked using
      a weighting approach matching from IBI-HPB patients' demographic distribution.
      RESULTS: A total of 5442 DVT and 6199 PE claims were identified. Employees with
      DVT lost 57 STD and 440 LTD days per disability incident. The average per claim
      productivity loss from STD and LTD was $7414 and $58181, respectively. Employees
      with PE lost 56 STD and 364 LTD days per disability incident. The average per
      claim productivity loss from STD and LTD was $7605 and $48,751, respectively.
      CONCLUSIONS: Deep vein thrombosis and PE impose substantial economic burdens.

PMID- 25046320
TI  - Association of a dietary inflammatory index with inflammatory indices and
      metabolic syndrome among police officers.
AB  - OBJECTIVES: To determine whether the dietary inflammatory index (DII) is
      associated with inflammatory or metabolic biomarkers and metabolic syndrome
      (MetSyn) among police officers. METHODS: Cross-sectional data from the Buffalo
      Cardio-Metabolic Occupational Police Stress study were derived from saliva and
      fasting blood samples, anthropometric measurements, long-term shiftwork
      histories, and demographic, stress/depression, and food frequency questionnaires
      (FFQs). Metabolic syndrome was defined using standard criteria. RESULTS: Officers
      in DII quartiles 2 to 4 were more likely to exceed a threshold of 3.0 mg/L for C
      reactive protein (odds ratio [OR] = 1.88; 95% confidence interval [95% CI] = 1.02
      to 3.45; OR = 2.17; 95% CI = 1.19 to 3.95; OR = 1.57; 95% CI = 0.85 to 2.88,
      respectively) compared with quartile 1. The glucose intolerance component of
      MetSyn was more prevalent among officers in DII quartile 4 than among those in
      quartile 1 (OR = 2.03; 95% CI = 1.08 to 3.82). CONCLUSIONS: A pro-inflammatory
      diet was associated with elevated CRP and with the glucose intolerance component
      of MetSyn.

PMID- 25046321
TI  - Suicide mortality among agricultural workers in a region with intensive tobacco
      farming and use of pesticides in Brazil.
AB  - OBJECTIVE: To investigate whether suicide risk among agricultural workers is
      higher in regions with heavier pesticide use and/or presence of tobacco farming.
      METHODS: Suicide mortality data were gathered from residents of the Brazilian
      state of Alagoas. Agricultural census data were used to arrange and classify
      Alagoas cities into distribution groups on the basis of variables concerning
      pesticide use and/or tobacco farming. Mortality odds ratio calculations were then
      used to compare suicide risk among agricultural and nonagricultural workers in
      different groups. RESULTS: Suicide risk was higher among agricultural workers
      than among nonagricultural workers, elevated in regions that used more
      pesticides, and greatest in regions that produced more tobacco. CONCLUSIONS: This
      is one of the first studies of its kind to suggest that combined effects of
      pesticide and tobacco exposure may be linked to higher suicide risk among
      agricultural workers.

PMID- 25046322
TI  - Impact of the combined use of benzodiazepines and opioids on workers'
      compensation claim cost.
AB  - OBJECTIVE: Study the use patterns and claim cost impact of prescription opioids
      and benzodiazepines in workers' compensation. METHODS: A cohort of 11,394 lost
      time claims filed with the Louisiana Workers' Compensation Corporation from 1999
      to 2002 was observed for 7 years post injuries. RESULTS: We found that
      benzodiazepines are almost always prescribed in combination with opioids. The
      odds ratios of benzodiazepines used alone, with short-acting opioids and with
      long-acting opioids for claims >=$100,000, were 2.74, 4.69, and 14.24,
      respectively (after controlling for gender, low back pain, marital status,
      attorney involvement, and each other). Average benzodiazepine daily dose
      increased to year 3 postinjury and plateaued thereafter, whereas the average
      opioid dose escalated each year postinjury. CONCLUSIONS: The addition of
      benzodiazepines to an opioid treatment regimen significantly increases workers'
      compensation costs.

PMID- 25046323
TI  - Evaluation of functional restoration outcomes for chronic disabling occupational
      cervical disorders.
AB  - OBJECTIVE: To systematically evaluate the effectiveness of an interdisciplinary
      functional restoration program (FRP) for treating chronic cervical disorders.
      METHODS: Consecutive chronic occupational lumbar disorder patients (n = 898) and
      chronic occupational cervical disorder patients (n = 215) were admitted to an FRP
      from 2001 to 2011. Patients were compared on demographics, work-related and
      psychosocial factors, and socioeconomic outcomes 1 year after discharge. RESULTS:
      Compared with lumbar patients, cervical patients were more likely to be female,
      have preadmission surgery, perform white-collar work, and have a longer time
      between injury and treatment admission. Cervical patients were similar to lumbar
      patients on most psychosocial self-report outcome measures. In addition, both
      groups exhibited high work return and work retention rates 1 year after FRP
      discharge. CONCLUSIONS: An FRP seems to be equally efficacious for treating both
      chronic occupational cervical and lumbar disorders.

PMID- 25046324
TI  - Occupational and biopsychosocial risk factors for carpal tunnel syndrome.
AB  - OBJECTIVE: To investigate a biopsychosocial model of risk for carpal tunnel
      syndrome (CTS). In addition, a host of exploratory psychosocial variables was
      investigated as potential risk factors for CTS. METHODS: A case-control design
      was used comparing 87 CTS and 74 sex-matched general orthopedic patients from an
      outpatient orthopedic clinic. All participants underwent the same diagnostic
      protocol (ie, physical evaluation and electrodiagnostic testing) and completed a
      self-report questionnaire assessing a wide range of potential occupational,
      personological, and psychosocial risk factors. RESULTS: Multiple logistic
      regression analyses revealed that occupational repetition, not engaging in
      vigorous exercise, physical activities with wrist strain, poorer physical health,
      and lower job satisfaction were significantly related to the presence of CTS.
      Obesity was borderline significantly related to the presence of CTS. CONCLUSIONS:
      The biopsychosocial model provides a useful heuristic for conceptualizing CTS
      risk among injured workers.

PMID- 25046325
TI  - Treatment of atrial fibrillation.

PMID- 25046327
TI  - Physicochemical and functional properties of rapeseed protein isolate: influence
      of antinutrient removal with acidified organic solvents from rapeseed meal.
AB  - The presence of antinutritional constituents in rapeseed protein products (RPI),
      such as polyphenols, phytates, allyl isothiocyanates, and glucosinolates, is a
      formidable constraint. The effect of antinutrient removal from rapeseed meal with
      an organic solvent mixture (methanol/acetone, 1:1 v/v, combined with an acid
      (hydrochloric, acetic, perchloric, trichloroacetic, phosphoric)) on the
      physicochemical and functional properties of RPI was investigated. The extraction
      resulted in a substantial reduction of antinutrients from RPI, especially
      polyphenols and phytates, with concomitant decreases in protein yield and
      solubility. Treatment harbored significant improvement in the degree of
      whiteness, which was highest in the perchloric acid case. Surface hydrophobicity
      and free sulfhydryl group of RPI changed considerably, with perchloric acid
      treated samples showing higher values, whereas the disulfide content remarkably
      increased in trichloroacetic acid- and phosphoric acid-treated samples,
      signifying aggregation. Intrinsic emission fluorescence and FTIR spectra showed
      significant changes in proteins' tertiary and secondary conformations, and the
      changes were more pronounced in samples treated with higher concentrations of
      acids. No appreciable alteration appeared among the electrophoretic profiles of
      proteins from pristine meal and those treated with lower levels of acids.
      Interfacial surface properties of proteins were variably improved by the solvent
      extraction, whereas the converse was true for their extent of denaturation. The
      results suggest that the physicochemical and conformational properties of RPI are
      closely related to its functional properties. 

PMID- 25046326
TI  - Cell fate regulated by nuclear factor-kappaB- and activator protein-1-dependent
      signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.
AB  - BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for
      malignant melanoma, but the wavelength responsible for the initiation of this
      disease is not fully elucidated. Solar UV induces multiple signalling pathways
      that are critical for initiation of apoptotic cell death as a cellular defence
      against malignant transformation. OBJECTIVES: To evaluate the involvement of the
      transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1 in
      the signalling pathways induced by UVA or UVB irradiation in human melanocytes.
      METHODS: Primary cultures of normal human melanocytes were irradiated with UVA or
      UVB, and the concomitant DNA damage and redox alterations were monitored. The
      resulting activation of the NF-kappaB and AP-1 signalling pathways and subsequent
      apoptosis were studied. RESULTS: UVB irradiation causes DNA damage detected as
      formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of
      8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate
      phosphorylation of c-Jun N-terminal protein kinase and extracellular signal
      regulated kinase, and the apoptosis signalling pathways converge into a common
      mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and
      prevents apoptosis upstream of lysosomal and mitochondrial membrane
      permeabilization, whereas inhibition of NF-kappaB by SN50 increases apoptosis.
      CONCLUSIONS: We conclude that AP-1 induces proapoptotic signalling, whereas NF
      kappaB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced
      cellular damage in human melanocytes, which might in turn impact melanoma
      development and progression.

PMID- 25046329
TI  - Cu-catalyzed Fe-driven C(sp)-C(sp) and C(s)p-C(sp2) cross-coupling: an access to
      1,3-diynes and 1,3-enynes.
AB  - An efficient Csp-Csp cross-coupling of alkynyl bromide and pinacol ester of
      alkynyl boronic acid catalyzed by CuFe2O4 nanoparticles has been accomplished in
      dimethyl carbonate to produce unsymmetric 1,3-diynes. This protocol is also
      extended for the Csp-Csp2 coupling of alkynyl bromide and alkenyl boronic acid to
      provide conjugated 1,3-enynes. The aliphatic, aromatic, and heteroaromatic
      alkynes couple with various substituted alkynyl/alkenyl boronates/boronic acids
      by this procedure to furnish a library of 1,3-diynes and enynes in high yields.
      The catalyst was easily separated by an external magnet and recycled 10 times. 

PMID- 25046328
TI  - Gd-Al co-doped mesoporous silica nanoparticles loaded with Ru(bpy)32+ as a dual
      modality probe for fluorescence and magnetic resonance imaging.
AB  - Mesoporous silica nanoparticles (MSNs) were co-doped with Gd(3+) and Al(3+) and
      then loaded with Ru(bpy)3(2+) by ion-exchange to prepare Ru/Gd-Al@MSNs. The as
      prepared Ru/Gd-Al@MSNs were applied as contrast agents for in vivo fluorescence
      and magnetic resonance (MR) dual-modality imaging with a mouse as a model. The
      effects of Al(3+) and MSNs on longitudinal relaxivity (r1) and fluorescence were
      investigated using a series of Gd-containing silica nanoparticles, including
      Gd@MSNs, Gd-Al@MSNs, and Ru/Gd-Al@nonporous silica nanoparticles. Co-doping with
      Al(3+) improved the loading of Gd(3+); the mesoporous structure improved the
      water exchange rate. The improvement enhanced the MR imaging efficiency of the
      Ru/Gd-Al@MSN probe. A higher relaxivity (19.2 mM(-1) s(-1)) was observed compared
      to that from a commercial contrast agent, Gd-diethylene triamine pentaacetic acid
      (Gd-DTPA). Importantly, the mesoporous structure provided a large specific
      surface area for the loading of Ru(bpy)3(2+) by a simple ion-exchange procedure.
      Intense red fluorescence was observed from Ru/Gd-Al@MSN probes. The versatility
      of Ru/Gd-Al@MSNs for dual-modality imaging was demonstrated using in vivo
      fluorescence imaging and T1-weighted MR imaging with a mouse model. The
      nanoparticles are biocompatible and may be attractive for clinical applications. 

PMID- 25046330
TI  - Key residues for the light regulation of the blue light-activated adenylyl
      cyclase from Beggiatoa sp.
AB  - Photoactivated adenylyl cyclases are powerful tools for optogenetics and for
      investigating signal transduction mechanisms in biological photoreceptors.
      Because of its large increase in enzyme activity in the light, the BLUF (blue
      light sensor using flavin adenine dinucleotide)-activated adenylyl cyclase (bPAC)
      from Beggiatoa sp. is a highly attractive model system for studying BLUF domain
      signaling. In this report, we studied the influence of site-directed mutations
      within the BLUF domain on the light regulation of the cyclase domain and
      determined key elements for signal transduction and color tuning. Photoactivation
      of the cyclase domain is accomplished via strand beta5 of the BLUF domain and
      involves the formation of helical structures in the cyclase domain as assigned by
      vibrational spectroscopy. In agreement with earlier studies, we observed severely
      impaired signaling in mutations directly on strand beta5 as well as in mutations
      affecting the hydrogen bond network around the flavin. Moreover, we identified a
      bPAC mutant with red-shifted absorbance and a decreased dark activity that is
      highly valuable for long-term optogenetic experiments. Additionally, we
      discovered a mutant that forms a stable neutral flavin semiquinone radical in the
      BLUF domain and surprisingly exhibits an inversion of light activation. 

PMID- 25046331
TI  - Fecal microbiota transplantation in the treatment of refractory Clostridium
      difficile infection in children: an update.
AB  - PURPOSE OF REVIEW: The use of transplanted fecal material for the treatment of
      diarrheal illness dates back to the fourth-century China. While fecal microbiota
      transplant has gained increasing popularity over the past 50 years for the
      treatment of refractory Clostridium difficile infections (RCDIs) in adults, it
      has only been recently utilized in children. The purpose of this article is to
      review the use of fecal microbiota transplant (FMT) in the treatment of pediatric
      RCDIs. RECENT FINDINGS: Minimal pediatric data, including few case reports and
      series, document the successful use of FMT for treatment of RCDI in the past 2
      years. Patients in these reports included otherwise healthy children, those with
      inflammatory bowel disease as well as significantly immunocompromised children.
      Donor fecal infusion via nasogastric tube, gastroscope or colonoscope in children
      aged 16 months and older demonstrated a high rate of symptom resolution and
      organism eradication. No complications to date have been reported in children who
      have undergone FMT. SUMMARY: FMT is emerging as a well-tolerated and effective
      treatment for RCDI in not only adults but also children.

PMID- 25046332
TI  - Laboratory and clinical evaluation of on-site urine drug testing.
AB  - AIM: Products for on-site urine drug testing offer the possibility to perform
      screening for drugs of abuse directly at the point-of-care. This is a well
      established routine in emergency and dependency clinics but further evaluation of
      performance is needed due to inherent limitations with the available products.
      METHODS: Urine drug testing by an on-site product was compared with routine
      laboratory methods. First, on-site testing was performed at the laboratory in
      addition to the routine method. Second, the on-site testing was performed at a
      dependency clinic and urine samples were subsequently sent to the laboratory for
      additional analytical investigation. RESULTS: The on-site testing products did
      not perform with assigned cut-off levels. The subjective reading between the
      presence of a spot (i.e. negative test result) being present or no spot (positive
      result) was difficult in 3.2% of the cases, and occurred for all parameters. The
      tests performed more accurately in drug negative samples (specificity 96%) but
      less accurately for detecting positives (sensitivity 79%). Of all incorrect
      results by the on-site test the proportion of false negatives was 42%. The
      overall agreement between on-site and laboratory testing was 95% in the
      laboratory study and 98% in the clinical study. CONCLUSION: Although a high
      degree of agreement was observed between on-site and routine laboratory urine
      drug testing, the performance of on-site testing was not acceptable due to
      significant number of false negative results. The limited sensitivity of on-site
      testing compared to laboratory testing reduces the applicability of these tests.

PMID- 25046333
TI  - Comparison of complement activity in adult and preterm sheep serum.
AB  - PROBLEM: Functional complement activity is routinely measured utilizing rabbit
      antibody-sensitized sheep erythrocytes. Due to complement inhibitor expression on
      erythrocytes, the development of an alternative method to measure complement
      function in sheep serum was required. METHOD OF STUDY: Several species of target
      erythrocyte and sensitizing antibody were investigated for improved measurement
      of complement function testing. RESULTS AND CONCLUSION: Guinea pig erythrocytes
      were identified as the optimal target, although sensitizing them with rabbit
      antiguinea pig erythrocyte antibody did not enhance the lysis by maternal sheep
      serum. In contrast, preterm neonatal sheep serum was unable to efficiently lyse
      guinea pig erythrocytes unless pre-sensitized with antibody. Further
      investigation revealed that maternal serum contained high levels of antibodies
      that cross-reacted with guinea pig and rabbit erythrocytes, while no cross
      reacting antierythrocyte antibodies were found in preterm neonatal serum.
      Therefore, unlike primates, rabbits, and guinea pigs, no transplacental transfer
      of maternal IgG to foetal sheep occurs. Use of exogenous complement regulators is
      often used to dissect the contribution of complement to disease pathogenesis;
      however, we found that while full-length soluble human complement receptor 1
      (sCR1, CDX-1135) was able to inhibit lysis of guinea pig erythrocytes by human
      and rat serum, no inhibition of sheep serum could be observed. Investigation of
      complement contribution to disease pathogenesis in the future will require the
      identification of an inhibitor that is effective against sheep complement.

PMID- 25046334
TI  - Excited states of proton-bound DNA/RNA base homodimers: pyrimidines.
AB  - We are presenting the electronic photofragment spectra of the protonated
      pyrimidine DNA base homodimers. Only the thymine dimer exhibits a well structured
      vibrational progression, while the protonated monomer shows broad vibrational
      bands. This shows that proton bonding can block some nonradiative processes
      present in the monomer. 

PMID- 25046335
TI  - Using informational connectivity to measure the synchronous emergence of fMRI
      multi-voxel information across time.
AB  - It is now appreciated that condition-relevant information can be present within
      distributed patterns of functional magnetic resonance imaging (fMRI) brain
      activity, even for conditions with similar levels of univariate activation. Multi
      voxel pattern (MVP) analysis has been used to decode this information with great
      success. FMRI investigators also often seek to understand how brain regions
      interact in interconnected networks, and use functional connectivity (FC) to
      identify regions that have correlated responses over time. Just as univariate
      analyses can be insensitive to information in MVPs, FC may not fully characterize
      the brain networks that process conditions with characteristic MVP signatures.
      The method described here, informational connectivity (IC), can identify regions
      with correlated changes in MVP-discriminability across time, revealing
      connectivity that is not accessible to FC. The method can be exploratory, using
      searchlights to identify seed-connected areas, or planned, between pre-selected
      regions-of-interest. The results can elucidate networks of regions that process
      MVP-related conditions, can breakdown MVPA searchlight maps into separate
      networks, or can be compared across tasks and patient groups. 

PMID- 25046336
TI  - Live imaging of Drosophila larval neuroblasts.
AB  - Stem cells divide asymmetrically to generate two progeny cells with unequal fate
      potential: a self-renewing stem cell and a differentiating cell. Given their
      relevance to development and disease, understanding the mechanisms that govern
      asymmetric stem cell division has been a robust area of study. Because they are
      genetically tractable and undergo successive rounds of cell division about once
      every hour, the stem cells of the Drosophila central nervous system, or
      neuroblasts, are indispensable models for the study of stem cell division. About
      100 neural stem cells are located near the surface of each of the two larval
      brain lobes, making this model system particularly useful for live imaging
      microscopy studies. In this work, we review several approaches widely used to
      visualize stem cell divisions, and we address the relative advantages and
      disadvantages of those techniques that employ dissociated versus intact brain
      tissues. We also detail our simplified protocol used to explant whole brains from
      third instar larvae for live cell imaging and fixed analysis applications. 

PMID- 25046338
TI  - Comparative effectiveness of topical drugs in dermatologic priority diseases:
      geometry of randomized trial networks.
AB  - Among the 100 initial priority topics for comparative effectiveness research,
      three concern topical drugs in the following dermatologic diseases: psoriasis,
      chronic lower-extremity wounds (CLEWs), and acne vulgaris (AV). Our objective was
      to explore the geometry of the corresponding networks of randomized controlled
      trials (RCTs). We performed a review of RCTs on topical drugs in psoriasis,
      CLEWs, and AV. We searched MEDLINE, Embase, and CENTRAL for published trials from
      2007 to 2012 and ClinicalTrials.gov for unpublished trials registered since 2011.
      RCTs comparing at least one topical treatment with any active or inactive
      comparator, regardless of RCT design and outcomes, were eligible. We produced
      network graphs (each node representing a treatment and links between nodes
      representing trials) and tested for co-occurrence (preference or avoidance of
      specific comparisons). We included 60 RCTs on psoriasis (14,255 patients) and 19
      registered RCTs, 50 of CLEWs (5,916 patients) and 7 registered RCTs, and 90 of AV
      (22,984 patients) and 21 registered RCTs. Head-to-head comparisons were made in
      78%, 32%, and 57% of published RCTs of these conditions, respectively. The co
      occurrence test suggested that no specific head-to-head comparison was
      significantly preferred or avoided (P-value=0.53, 0.20, and 0.57, respectively).
      This study has limitations, the main being that the search period was restricted
      to 5 years. In conclusion, more comparative effectiveness trials are needed for
      CLEWs, for which head-to-head comparisons are fewer than those for psoriasis and
      AV. 

PMID- 25046337
TI  - Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous
      urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo
      controlled study.
AB  - ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to
      evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for
      24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria
      (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed
      doses. Patients aged 12-75 years with CIU/CSU who remained symptomatic despite
      treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a
      double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or
      placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary
      end point was change from baseline in weekly itch severity score (ISS) at week
      12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg
      n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo
      (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional
      2.96 points (95% confidence interval (CI): -4.71 to -1.21; P=0.0010), 2.95 points
      (95% CI: -4.72 to -1.18; P=0.0012), and 5.80 points (95% CI: -7.49 to -4.10;
      P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups
      (n=81), respectively. The omalizumab 300-mg group met all nine secondary end
      points, including a significant decrease in the duration of time to reach
      minimally important difference response (?5-point decrease) in weekly ISS
      (P<0.0001) and higher percentages of patients with well-controlled symptoms
      (urticaria activity score over 7 days (UAS7) ?6: 51.9% vs. 11.3%; P<0.0001) and
      complete response (UAS7=0: 35.8% vs. 8.8%; P<0.0001) versus placebo. During the
      24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the
      omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a
      serious adverse event. Omalizumab 300 mg administered subcutaneously every 4
      weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU
      patients who remained symptomatic despite treatment with approved doses of H1
      antihistamines. 

PMID- 25046339
TI  - IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis.
AB  - Psoriasis is a common chronic inflammatory disease with characteristic skin
      alterations and functions as a model of immune-mediated disorders. Cytokines have
      a key role in psoriasis pathogenesis. Here, we demonstrated that out of 30
      individually quantified cytokines, IL-19 showed the strongest differential
      expression between psoriatic lesions and healthy skin. Cutaneous IL-19
      overproduction was reflected by elevated IL-19 blood levels that correlated with
      psoriasis severity. Accordingly, anti-psoriatic therapies substantially reduced
      both cutaneous and systemic IL-19 levels. IL-19 production was induced in
      keratinocytes by IL-17A and was further amplified by tumor necrosis factor-alpha
      and IL-22. Among skin cells, keratinocytes were found to be important targets of
      IL-19. IL-19 alone, however, regulated only a few keratinocyte functions. While
      increasing the production of S100A7/8/9 and, to a moderate extent, also IL-1beta,
      IL-20, chemokine C-X-C motif ligand 8, and matrix metalloproteinase 1, IL-19 had
      no clear influence on the differentiation, proliferation, or migration of these
      cells. Importantly, IL-19 amplified many IL-17A effects on keratinocytes,
      including the induction of beta-defensins, IL-19, IL-23p19, and T helper type 17
      cell- and neutrophil-attracting chemokines. In summary, IL-19 as a component of
      the IL-23/IL-17 axis strengthens the IL-17A action and might be a biomarker for
      the activity of this axis in chronic inflammatory disorders. 

PMID- 25046340
TI  - Ultrafast dynamics of surface plasmons in InAs by time-resolved infrared
      nanospectroscopy.
AB  - We report on time-resolved mid-infrared (mid-IR) near-field spectroscopy of the
      narrow bandgap semiconductor InAs. The dominant effect we observed pertains to
      the dynamics of photoexcited carriers and associated surface plasmons. A novel
      combination of pump-probe techniques and near-field nanospectroscopy accesses
      high momentum plasmons and demonstrates efficient, subpicosecond photomodulation
      of the surface plasmon dispersion with subsequent tens of picoseconds decay under
      ambient conditions. The photoinduced change of the probe intensity due to
      plasmons in InAs is found to exceed that of other mid-IR or near-IR media by 1-2
      orders of magnitude. Remarkably, the required control pulse fluence is as low as
      60 MUJ/cm(2), much smaller than fluences of ~ 1-10 mJ/cm(2) previously utilized
      in ultrafast control of near-IR plasmonics. These low excitation densities are
      easily attained with a standard 1.56 MUm fiber laser. Thus, InAs--a common
      semiconductor with favorable plasmonic properties such as a low effective mass-
      has the potential to become an important building block of optically controlled
      plasmonic devices operating at infrared frequencies.

PMID- 25046341
TI  - Interobserver variability for the WHO classification of pulmonary carcinoids.
AB  - Pulmonary carcinoids are neuroendocrine tumors histopathologically subclassified
      into typical (TC; no necrosis, <2 mitoses per 2 mm) and atypical (AC; necrosis or
      2 to 10 mitoses per 2 mm). The reproducibility of lung carcinoid classification,
      however, has not been extensively studied and may be hampered by the presence of
      pyknotic apoptosis mimicking mitotic figures. Furthermore, prediction of
      prognosis based on histopathology varies, especially for ACs. We examined the
      presence of interobserver variation between 5 experienced pulmonary pathologists
      who reviewed 123 originally diagnosed pulmonary carcinoid cases. The tumors were
      subsequently redistributed over 3 groups: unanimously classified cases, consensus
      cases (4/5 pathologists rendered identical diagnosis), and disagreement cases
      (divergent diagnosis by >=2 assessors). kappa-values were calculated, and results
      were correlated with clinical follow-up and molecular data. When focusing on the
      114/123 cases unanimously classified as pulmonary carcinoids, the interobserver
      agreement was only fair (kappa=0.32). Of these 114 cases, 55% were unanimously
      classified, 25% reached consensus classification, and for 19% there was no
      consensus. ACs were significantly more often in the latter category (P=0.00038).
      The designation of TCs and ACs by >=3 assessors was not associated with prognosis
      (P=0.11). However, when disagreement cases were allocated on the basis of Ki-67
      proliferative index (<5%; >=5%) or nuclear orthopedia homeobox immunostaining (+;
      -), correlation with prognosis improved significantly (P=0.00040 and 0.0024,
      respectively). In conclusion, there is a considerable interobserver variation in
      the histopathologic classification of lung carcinoids, in particular concerning
      ACs. Additional immunomarkers such as Ki-67 or orthopedia homeobox may improve
      classification and prediction of prognosis. 

PMID- 25046342
TI  - A subset of malignant phyllodes tumors express p63 and p40: a diagnostic pitfall
      in breast core needle biopsies.
AB  - Breast phyllodes tumors are rare fibroepithelial neoplasms of variable grade, and
      one key differential of malignant phyllodes on core biopsy is sarcomatoid
      carcinoma. p63 is reported to be sensitive and specific for sarcomatoid
      carcinoma, with rare expression in phyllodes in limited series. The p63 deltaNp63
      isoform, p40, is postulated to be more specific for squamous differentiation but
      has not previously been evaluated in breast phyllodes or sarcomatoid carcinoma.
      Tissue microarrays containing 34 unambiguous phyllodes tumors (10 benign, 10
      borderline, 14 malignant), 13 sarcomatoid carcinomas, and 10 fibroadenomas were
      labeled by immunohistochemistry for p63, p40, CD34, and cytokeratins AE1/AE3,
      34betaE12, and CK8/18. No borderline phyllodes tumor, benign phyllodes tumor, or
      fibroadenoma labeled with p63, p40, or cytokeratin. However, p63 labeled 57%
      malignant phyllodes tumors and 62% sarcomatoid carcinomas, and p40 labeled 29%
      malignant phyllodes (focal) and 46% sarcomatoid carcinomas. Among established
      markers, cytokeratins labeled 21% malignant phyllodes tumors (focal) and 100%
      sarcomatoid carcinomas. CD34 labeled 57% malignant phyllodes tumors and no
      sarcomatoid carcinomas. Focal p63, p40, and cytokeratin labeling can be seen in
      malignant phyllodes tumors but not in lower-grade fibroepithelial lesions, and
      immunoreactivity with these markers alone is not diagnostic of sarcomatoid
      carcinoma on core needle biopsy. In the differential diagnosis of malignant
      phyllodes, p40 is a more specific but less sensitive marker of sarcomatoid
      carcinoma than p63. These results are consistent with the sarcoma literature in
      which p63 labeling has been increasingly reported and suggest caution in
      classifying malignant spindle cell tumors of the breast on core biopsy. 

PMID- 25046343
TI  - Technology-based interventions for psychiatric illnesses: improving care, one
      patient at a time.
AB  - Worldwide, individuals with severe psychiatric illnesses struggle to receive
      evidence-based care. While science has made remarkably slow progress in the
      development and implementation of effective psychiatric treatments, we have
      witnessed enormous progress in the emergence and global penetration of personal
      computing technology. The present paper examines how digital resources that are
      already widespread (e.g., smartphones, laptop computers), can be leveraged to
      support psychiatric care. These instruments and implementation strategies can
      increase patient access to evidenced-based care, help individuals overcome the
      barriers associated with the stigma of mental illness, and facilitate new
      treatment paradigms that harness wireless communication, sensors and the
      Internet, to enhance treatment potency. Innovative digital treatment programmes
      that have been used successfully with a range of conditions (i.e., schizophrenia,
      posttraumatic stress disorder and borderline personality disorder) are presented
      in the paper to demonstrate the utility and potential impact of technology-based
      interventions in the years ahead. 

PMID- 25046344
TI  - Anaerobic fungi (phylum Neocallimastigomycota): advances in understanding their
      taxonomy, life cycle, ecology, role and biotechnological potential.
AB  - Anaerobic fungi (phylum Neocallimastigomycota) inhabit the gastrointestinal tract
      of mammalian herbivores, where they play an important role in the degradation of
      plant material. The Neocallimastigomycota represent the earliest diverging
      lineage of the zoosporic fungi; however, understanding of the relationships of
      the different taxa (both genera and species) within this phylum is in need of
      revision. Issues exist with the current approaches used for their identification
      and classification, and recent evidence suggests the presence of several novel
      taxa (potential candidate genera) that remain to be characterised. The life cycle
      and role of anaerobic fungi has been well characterised in the rumen, but not
      elsewhere in the ruminant alimentary tract. Greater understanding of the
      'resistant' phase(s) of their life cycle is needed, as is study of their role and
      significance in other herbivores. Biotechnological application of anaerobic
      fungi, and their highly active cellulolytic and hemi-cellulolytic enzymes, has
      been a rapidly increasing area of research and development in the last decade.
      The move towards understanding of anaerobic fungi using -omics based (genomic,
      transcriptomic and proteomic) approaches is starting to yield valuable insights
      into the unique cellular processes, evolutionary history, metabolic capabilities
      and adaptations that exist within the Neocallimastigomycota. 

PMID- 25046346
TI  - Reaction mechanism of epoxide cycloaddition to CO2 catalyzed by salen-M (M = Co,
      Al, Zn).
AB  - We propose a catalytic mechanism for the cycloaddition of epoxide to carbon
      dioxide catalyzed by salen-M (M = Co, Zn, Al) based on density functional theory
      calculations. The catalytic reaction follows a single-site mechanism rather than
      a bimetallic-site mechanism, which includes four steps: epoxide adsorption by
      salen-M, ring opening of epoxide, CO2 insertion, and intramolecular
      rearrangement. Our calculation results showed that the highest reaction barrier
      for salen-Co catalyst is only 9.94 kcal/mol, which is lower than that of salen-Al
      (14.38 kcal/mol) and salen-Zn (13.05 kcal/mol). The results indicate that the
      reaction catalyzed by salen-Al, salen-Co, or salen-Zn can occur at room
      temperature and atmospheric pressure, which is in agreement with experimental
      results. The mechanism can be used for the design of a novel catalyst for this
      reaction. 

PMID- 25046345
TI  - Discovering protein interactions and characterizing protein function using
      HaloTag technology.
AB  - Research in proteomics has exploded in recent years with advances in mass
      spectrometry capabilities that have led to the characterization of numerous
      proteomes, including those from viruses, bacteria, and yeast. In comparison,
      analysis of the human proteome lags behind, partially due to the sheer number of
      proteins which must be studied, but also the complexity of networks and
      interactions these present. To specifically address the challenges of
      understanding the human proteome, we have developed HaloTag technology for
      protein isolation, particularly strong for isolation of multiprotein complexes
      and allowing more efficient capture of weak or transient interactions and/or
      proteins in low abundance. HaloTag is a genetically encoded protein fusion tag,
      designed for covalent, specific, and rapid immobilization or labelling of
      proteins with various ligands. Leveraging these properties, numerous applications
      for mammalian cells were developed to characterize protein function and here we
      present methodologies including: protein pull-downs used for discovery of novel
      interactions or functional assays, and cellular localization. We find significant
      advantages in the speed, specificity, and covalent capture of fusion proteins to
      surfaces for proteomic analysis as compared to other traditional non-covalent
      approaches. We demonstrate these and the broad utility of the technology using
      two important epigenetic proteins as examples, the human bromodomain protein
      BRD4, and histone deacetylase HDAC1. These examples demonstrate the power of this
      technology in enabling the discovery of novel interactions and characterizing
      cellular localization in eukaryotes, which will together further understanding of
      human functional proteomics.

PMID- 25046347
TI  - Meaningfulness of service and marital satisfaction in Army couples.
AB  - The vast numbers of military service members who have been deployed since 2001
      highlights the need to better understand relationships of military couples. A
      unique consideration in military couples is the concept of meaningfulness of
      service, or the value service members and their partners place on military
      service in spite of the sacrifices it requires. In a sample of 606 Army couples,
      the authors used path analysis to examine how male service members' and female
      spouses' perceived meaningfulness of service added to the prediction of marital
      satisfaction in both members of the couple, when accounting for service members'
      PTSD symptoms. Spouses' perceived meaningfulness of service was linked with
      higher marital satisfaction in spouses, regardless of service member's perceived
      meaningfulness of service. Service members' perceived meaningfulness of service
      was also associated with increased marital satisfaction in service members, but
      only when their spouses also perceived higher meaningfulness. There were no
      significant interactions between service members' PTSD and either partner's
      perceived meaningfulness. Implications for enhanced attention to spousal
      perceptions of meaningfulness of service are discussed.

PMID- 25046348
TI  - Diagnosis and management of iatrogenic endoscopic perforations: European Society
      of Gastrointestinal Endoscopy (ESGE) Position Statement.
AB  - This Position Paper is an official statement of the European Society of
      Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of
      iatrogenic perforation occurring during diagnostic or therapeutic digestive
      endoscopic procedures. Main recommendations 1 ESGE recommends that each center
      implements a written policy regarding the management of iatrogenic perforation,
      including the definition of procedures that carry a high risk of this
      complication. This policy should be shared with the radiologists and surgeons at
      each center. 2 In the case of an endoscopically identified perforation, ESGE
      recommends that the endoscopist reports: its size and location with a picture;
      endoscopic treatment that might have been possible; whether carbon dioxide or air
      was used for insufflation; and the standard report information. 3 ESGE recommends
      that symptoms or signs suggestive of iatrogenic perforation after an endoscopic
      procedure should be carefully evaluated and documented, possibly with a computed
      tomography (CT) scan, in order to prevent any diagnostic delay. 4 ESGE recommends
      that endoscopic closure should be considered depending on the type of
      perforation, its size, and the endoscopist expertise available at the center. A
      switch to carbon dioxide insufflation, the diversion of luminal content, and
      decompression of tension pneumoperitoneum or tension pneumothorax should also be
      done. 5 After closure of an iatrogenic perforation using an endoscopic method,
      ESGE recommends that further management should be based on the estimated success
      of the endoscopic closure and on the general clinical condition of the patient.
      In the case of no or failed endoscopic closure of the iatrogenic perforation, and
      in patients whose clinical condition is deteriorating, hospitalization and
      surgical consultation are recommended. 

PMID- 25046350
TI  - Limb bone morphology, bone strength, and cursoriality in lagomorphs.
AB  - The primary aim of this study is to broadly evaluate the relationship between
      cursoriality (i.e. anatomical and physiological specialization for running) and
      limb bone morphology in lagomorphs. Relative to most previous studies of
      cursoriality, our focus on a size-restricted, taxonomically narrow group of
      mammals permits us to evaluate the degree to which 'cursorial specialization'
      affects locomotor anatomy independently of broader allometric and phylogenetic
      trends that might obscure such a relationship. We collected linear morphometrics
      and MUCT data on 737 limb bones covering three lagomorph species that differ in
      degree of cursoriality: pikas (Ochotona princeps, non-cursorial), jackrabbits
      (Lepus californicus, highly cursorial), and rabbits (Sylvilagus bachmani, level
      of cursoriality intermediate between pikas and jackrabbits). We evaluated two
      hypotheses: cursoriality should be associated with (i) lower limb joint
      mechanical advantage (i.e. high 'displacement advantage', permitting more
      cursorial species to cycle their limbs more quickly) and (ii) longer, more
      gracile limb bones, particularly at the distal segments (as a means of decreasing
      rotational inertia). As predicted, highly cursorial jackrabbits are typically
      marked by the lowest mechanical advantage and the longest distal segments, non
      cursorial pikas display the highest mechanical advantage and the shortest distal
      segments, and rabbits generally display intermediate values for these variables.
      Variation in long bone robusticity followed a proximodistal gradient. Whereas
      proximal limb bone robusticity declined with cursoriality, distal limb bone
      robusticity generally remained constant across the three species. The association
      between long, structurally gracile limb bones and decreased maximal bending
      strength suggests that the more cursorial lagomorphs compromise proximal limb
      bone integrity to improve locomotor economy. In contrast, the integrity of distal
      limb bones is maintained with increasing cursoriality, suggesting that the safety
      factor takes priority over locomotor economy in those regions of the postcranial
      skeleton that experience higher loading during locomotion. Overall, these
      findings support the hypothesis that cursoriality is associated with a common
      suite of morphological adaptations across a range of body sizes and radiations.

PMID- 25046351
TI  - A pilot study of a novel dual--pulsed 1064 nm Q-switched Nd: YAG laser to treat
      Riehl's melanosis.
AB  - The treatment of Riehl's melanosis is difficult and challenging. Recently, a low
      fluence 1064-nm quality (Q)-switched neodymium: yttrium-aluminum-garnet (Nd: YAG)
      laser method, referred to as 'laser toning', has been used in the treatment of
      melasma in Asian countries. We present here a series of cases of Riehl's
      melanosis that were treated effectively with a novel Q-switched Nd: YAG laser
      that was operated as a dual-pulse at half-fluence and 140-MUs intervals.

PMID- 25046352
TI  - Efficient polymer solar cells fabricated on poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate)-etched old indium tin oxide
      substrates.
AB  - In organic electronic devices, indium tin oxide (ITO) and poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) are the most common
      transparent electrode and anodic buffer layer materials, respectively. A
      widespread concern is that PEDOT:PSS is acidic and etches ITO. We show that this
      issue is not serious: only a few nanometers of ITO are etched in typical device
      processing conditions and storage thereafter; conductivity losses are affordable;
      and optical transmission gains further offset these losses. Organic photovoltaic
      (OPV) devices fabricated on old ITO (with PEDOT:PSS history) were similar or
      higher in efficiency than devices on fresh ITO. Poly[[4,8-bis[(2
      ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2
      ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7) devices on old ITO showed
      efficiencies up to 9.24% compared to 8.72% efficient devices on fresh ITO. This
      reusability of ITO can be impactful for economics of organic electronics because
      ITO accounts for almost 90% of energy embedded in devices, such as OPVs. 

PMID- 25046349
TI  - Contemporary practice and technique-related outcomes for radical prostatectomy in
      the UK: a report of national outcomes.
AB  - OBJECTIVE: To determine current radical prostatectomy (RP) practice in the UK and
      compare surgical outcomes between techniques. PATIENTS AND METHODS: All RPs
      performed between 1 January 2011 and 31 December 2011 in the UK with data entered
      into the British Association of Urological Surgeons (BAUS) database, were
      identified for analysis. Overall surgical outcomes were assessed and subgroup
      analyses of these outcomes, based on operative technique [open RP (ORP),
      laparoscopic RP (LRP) and robot-assisted laparoscopic RP (RALP)], were made.
      Continuous variables were compared using the Mann-Whitney U-test and categorical
      variables using the Pearson chi-squared test. Univariate and multivariate binary
      regression analyses were performed to assess the effect of patient, surgeon and
      technique-related variables on surgical outcomes. RESULTS: During the study
      period 2163 RPs were performed by 115 consultants with a median (range) of 11 (1
      154) cases/consultant. Most RPs were performed laparoscopically (ORP 25.8%, LRP
      54.6%, RALP 19.6%) and those performing minimally invasive techniques are more
      likely to have a higher annual case volume with <1% ORP, 39% LRP and 62% RALP
      being performed by consultants with an annual caseload of >50 cases/year. Most
      patients were classified as having intermediate- or high-risk disease
      preoperatively (1596 patients, 82.5%) and this increased to 97.2% (1649) on
      postoperative risk stratification. The overall intraoperative complication rate
      was 14.2% and was significantly greater for LRP (17.8%) vs ORP (8.2%) and RALP
      (12.4%), (P < 0.001). In all, 71% of patients had an estimated blood loss (EBL)
      of <500 mL, although there were significantly more patients undergoing ORP with
      >500, > 1000 and >2000 mL EBL compared with the other techniques (P < 0.001). The
      postoperative complication rate was 10.7% overall, with a significantly greater
      postoperative complication rate in the LRP group (LRP 14.6%, ORP 8.8% and RALP
      10.3% respectively, P = 0.007). Positive surgical margin (PSM) rates were 17.5%
      for pT2 disease and 42.3% for pT3 disease. The PSM rate was significantly lower
      in the RALP patients compared with the ORP patients for those with pT2 disease (P
      = 0.025), while there was no difference between ORP and LRP (ORP 21.7%, LRP 18.1%
      and RALP 13.0%). There was no significant difference in the PSM rate in pT3
      disease between surgical techniques. CONCLUSION: Most RPs in the UK are performed
      using minimally invasive techniques, which offer reduced blood loss and
      transfusion rates compared with ORP. The operation time, complication rate, PSM
      rates, and association with higher volume practice support RALP as the minimally
      invasive technique of choice, which could have implications for regions without
      access to such services. The disparity in outcomes between this national study
      and high-volume single centres, most probably reflects the low median national
      case volume, and combined with the positive effect of high case volume on
      multivariate analysis of surgical outcomes and PSM rates, strengthens the
      argument for centralisation of services.

PMID- 25046353
TI  - Two new coordination polymers, a trinuclear metal complex and their
      interconversion depending on the solvent.
AB  - Two new 1-D coordination polymers and a discrete trinuclear complex with a double
      ring framework were synthesized and structurally characterized. The unique
      irreversible conversion from one of the 1-D coordination polymers to the
      trinuclear complex by contact with MeCN is described. 

PMID- 25046355
TI  - Thermal- and light-induced spin-crossover bistability in a disrupted Hofmann-type
      3D framework.
AB  - The expected 3D and 2D topologies resulting from combining approximately linear
      bis- or monopyridyl ligands with [Fe(II)M(II)(CN)4] (M(II) = Pt, Pd, Ni) 4,4-grid
      sheets are well established. We show here the magnetic and structural
      consequences of incorporating a bent bispyridyl linker ligand in combination with
      [Fe(II)Pt(II)(CN)4] to form the material [Fe(H2O)2Fe(DPSe)2(Pt(CN)4)2].3EtOH
      (DPSe = 4,4'-dipyridylselenide). Structural investigations reveal an unusual
      connectivity loosely resembling a 3D Hofmann topology where (1) there are two
      distinct local iron(II) environments, [Fe(II)N6] (Fe1) and [Fe(II)N4O2] (Fe2),
      (2) as a consequence of axial water coordination to Fe2, there are "holes" in the
      [Fe(II)Pt(II)(CN)4] 4,4 sheets because of some of the cyanido ligands being
      terminal rather than bridging, and (3) bridging of adjacent sheets occurs only
      through one in two DPSe ligands, with the other acting as a terminal ligand
      binding through only one pyridyl group. The magnetic properties are defined by
      this unusual topology such that only Fe1 is in the appropriate environment for a
      high-spin to low-spin transition to occur. Magnetic susceptibility data reveal a
      complete and abrupt hysteretic spin transition (T(1/2)? = 120 K and T(1/2)? = 130
      K) of this iron(II) site; Fe2 remains high-spin. This material additionally
      exhibits a photomagnetic response (uncommon for Hofmann-related materials),
      showing light-induced excited spin-state trapping [LIESST; T(LIESST) = 61 K] with
      associated bistability evidenced in a hysteresis loop (T(1/2)? = 60 K and T(1/2)?
      = 66 K).

PMID- 25046354
TI  - Emergency preparedness law and willingness to respond in the EMS workforce.
AB  - INTRODUCTION: For effective responses to emergencies, individuals must have the
      ability to respond and also be willing to participate in the response. A growing
      body of research points to gaps in response willingness among several
      occupational cohorts with response duties, including the Emergency Medical
      Services (EMS) workforce. Willingness to respond is particularly important during
      an influenza or other pandemic, due to increased demands on EMS workers and the
      potential for workforces to be depleted if responders contract influenza or stay
      home to care for sick dependents. State emergency preparedness laws are one
      possible avenue to improve willingness to respond. Hypothesis Presence of certain
      state-level emergency preparedness laws (ie, ability to declare a public health
      emergency; requirement to create a public health emergency plan; priority access
      to health resources for responders) is associated with willingness to respond
      among EMS workers. METHODS: Four hundred twenty-one EMS workers from the National
      Registry of Emergency Medical Technicians' (NREMT's) mid-year Longitudinal EMT
      Attributes and Demographics Study (LEADS) were studied. The survey, which
      included questions about willingness to respond during an influenza pandemic, was
      fielded from May through June 2009. Survey data were merged with data about the
      presence or absence of the three emergency preparedness laws of interest in each
      of the 50 US states. Unadjusted logistic regression analyses were performed with
      the presence/absence of each law and were adjusted for respondents'
      demographic/locale characteristics. RESULTS: Compared to EMS workers in states
      that did not allow the government to declare a public health emergency, those in
      states that permitted such declarations were more likely to report that they were
      willing to respond during an influenza pandemic. In adjusted and unadjusted
      analyses, this difference was not statistically significant. Similar results were
      found for the other state-level emergency preparedness laws of interest.
      CONCLUSION: While state-level emergency preparedness laws are not associated with
      willingness to respond, recent research suggests that inconsistencies between the
      perceived and objective legal environments for EMS workers could be an
      alternative explanation for this study's findings. Educational efforts within the
      EMS workforce and more prominent state-level implementation of emergency
      preparedness laws should be considered as a means to raise awareness of these
      laws. These types of actions are important steps toward determining whether state
      level emergency preparedness laws have the potential to promote response
      willingness among EMS workers.

PMID- 25046356
TI  - Energetics of CO2 and H2O adsorption on zinc oxide.
AB  - Adsorption of H2O and CO2 on zinc oxide surfaces was studied by gas adsorption
      calorimetry on nanocrystalline samples prepared by laser evaporation in oxygen to
      minimize surface impurities and degassed at 450  degrees C. Differential
      enthalpies of H2O and CO2 chemisorption are in the range -150 +/-10 kJ/mol and 
      110 +/-10 kJ/mol up to a coverage of 2 molecules per nm(2). Integral enthalpy of
      chemisorption for H2O is -96.8 +/-2.5 kJ/mol at 5.6 H2O/nm(2) when enthalpy of
      water condensation is reached, and for CO2 is -96.6 +/-2.5 kJ/mol at 2.6
      CO2/nm(2) when adsorption ceases. These values are consistent with those reported
      for ZnO prepared by other methods after similar degas conditions. The similar
      energetics suggests possible competition of CO2 and H2O for binding to ZnO
      surfaces. Exposure of bulk and nanocrystalline ZnO with preadsorbed CO2 to water
      vapor results in partial displacement of CO2 by H2O. In contrast, temperature
      programmed desorption (TPD) indicates that a small fraction of CO2 is retained on
      ZnO surfaces up to 800  degrees C, under conditions where all H2O is desorbed,
      with adsorption energies near -200 kJ/mol. Although molecular mechanisms of
      adsorption were not studied, the thermodynamic data are consistent with
      dissociative adsorption of H2O at low coverage and with several different modes
      of CO2 binding. 

PMID- 25046357
TI  - Dilational surface elasticity of spread monolayers of polystyrene microparticles.
AB  - The dependence of the dilational surface elasticity on the surface pressure of
      the spread monolayers of polystyrene microparticles is studied at the water-air
      interface. The surface rheological measurements together with the data from
      optical methods allow the division of the whole range of surface pressures into
      three zones characterized by different monolayer structures. The extremely high
      surface elasticity (~500 mN m(-1)) at surface pressures close to 30 mN m(-1) is
      similar to the results for the adsorption layer of the complexes formed between
      silica particles and surfactant molecules and is probably caused by strong
      hydrophobic attraction between the particles. At the same time, some other
      characteristic features of the viscoelasticity of the monolayers of polysterene
      microparticles differ strongly from the properties of previously studied systems.

PMID- 25046358
TI  - A novel small-molecule compound diaporine A inhibits non-small cell lung cancer
      growth by regulating miR-99a/mTOR signaling.
AB  - MicroRNAs (miRNAs) dysregulation is critically involved in lung cancer.
      Regulating miRNAs by natural agents may be a new strategy for cancer treatment.
      We previously found that a novel small-molecule compound diaporine A (D261), a
      natural product of endophytic fungus 3lp-10, had potential anti-cancer activites.
      In the present study, the inhibitory effect of D261 on non-small cell lung cancer
      (NSCLC) growth and its possible mechanisms involving miRNA regulation were
      investigated. By cell viability assay, cell proliferation analysis, and clonal
      growth assay, we proved that D261 effectively inhibited the proliferation of
      NSCLC cells (NCI-H460 and A549) in vitro. Administration of D261 (5 mg/kg) to NCI
      H460 xenografts bearing mice also inhibited tumor growth and decreased the
      expression of cell proliferation regulator, midkine. Moreover, D261 induced cell
      cycle arrest with a reduced expression of various G 1/S transition-related
      molecules including cyclin D1, cyclin E1, CDK4, and CDK2, but without influencing
      apoptosis in NSCLC cells. Intriguingly, D261 modified expressions of some miRNAs
      and especially upregulated miR-99a, whose direct target was mammalian target of
      rapamycin (mTOR). Furthermore, overexpression of miR-99a antagonized the anti
      tumor actions of D261 including the suppression of mTOR pathway activation, cell
      cycle-related proteins and cell growth. In addition, blocking of miR-99a
      expression by transfection of miR-99a inhibitors before D261 treatment
      counteracted the anti-tumor effects of D261. These data suggest that miR-99a/mTOR
      pathway was involved in D261-induced tumor suppression in NSCLC cells. D261 might
      be a potent anti-cancer agent by upregulating miR-99a expression. 

PMID- 25046360
TI  - An increased proportion of circulating Th22 and Tc22 cells in psoriasis.
AB  - Psoriasis is a common dermatosis mediated by T cells. This study investigated the
      correlation of Th22 cells and Tc22 cells with psoriasis. A total of 30 psoriasis
      patients and 11 age- and sex-matched healthy controls were recruited for this
      study. The proportions of circulating Th22 and Tc22 cells, expression of aryl
      hydrocarbon receptor, and IL-22 levels in the psoriasis patients were
      significantly higher than those in the control subjects (p<0.05). There was a
      positive correlation between the proportion of circulating Th22 cells, IL-22
      levels, and PASI score. The IL-22 levels and PASI score were also positively
      correlated. There was no correlation between the proportion of circulating Tc22
      cells and IL-22 level or PASI score. These data are consistent with Th22 cells
      involvement in the pathogenesis of psoriasis. 

PMID- 25046359
TI  - Proton T2 measurement and quantification of lactate in brain tumors by MRS at 3
      Tesla in vivo.
AB  - PURPOSE: To evaluate the T2 relaxation time of lactate (Lac) in brain tumors and
      the correlation of the T2 and concentration with tumor grades. METHODS: Eight
      pairs of the subecho time sets of point-resolved spectroscopy were selected
      between 58 and 268 ms, with numerical and phantom analyses, for Lac T2
      measurement. In vivo spectra were acquired from 24 subjects with gliomas (13 low
      grade and 11 high grade) and analyzed with LCModel using numerically-calculated
      basis spectra. The metabolite T2 relaxation time was obtained from
      monoexponential fitting of the multi-echo time (TE) signal estimates versus TE.
      The metabolite concentration was estimated from the zero-TE extrapolation of the
      T2 fits. RESULTS: The Lac T2 was estimated to be approximately 240 ms, without a
      significant difference between low and high grade tumors. The Lac concentration
      was estimated to be 4.1 +/- 3.4 and 7.0 +/- 4.7 mM for low and high grades
      respectively, but the difference was not significant. CONCLUSION: The Lac T2 was
      similar among gliomas regardless of their tumor grades. This suggests that the T2
      value from this study may be applicable to obtain the T2 relaxation-free
      estimates of Lac in a subset of brain tumors.

PMID- 25046361
TI  - Monitoring mechanisms in visual search: an fMRI study.
AB  - This fMRI study investigates the neural underpinning and the cognitive factors
      associated with monitoring in visual search. A visual search task was designed by
      pseudo-randomly mixing four experimental conditions, which were obtained through
      the factorial combination of salience (pop-out vs. non pop-out) and target
      presence (present vs. absent). The fastest responses were obtained when a salient
      target was presented, while responses were slowest with target-absent conditions,
      which required extensive evaluation of the visual scene. Partial Least Square
      multivariate analysis was used to analyze the fMRI data. The first Latent
      Variable revealed a set of fronto-parietal and occipital regions, which was
      cohesively activated especially when the presence of the target stimulus was not
      easy to discard, such as when all stimuli in the visual scene were non-targets or
      when one stimulus among the rest was salient (pop-out) but not a target. The most
      extensive and robust activation within this cohesive set of regions was located
      in the right inferior/middle frontal gyrus. This finding corroborates evidence in
      favor of a role of the right lateral prefrontal cortex, and associated regions,
      for evaluative operations, extending previous findings to the visual search
      domain. 

PMID- 25046362
TI  - Nickel-catalyzed C-H coupling with allyl phosphates: a site-selective synthetic
      route to linear allylarenes.
AB  - It is reported that a nickel/phosphine catalyst allows the C-H allylation to
      occur effectively with the allyl site selectivity predominantly governed by
      steric effects. This reaction provides a facile and predictable route for the
      selective preparation of linear allylarenes from readily available benzamides and
      allyl phosphates. 

PMID- 25046363
TI  - Kinetic analysis of hyperpolarized data with minimum a priori knowledge: Hybrid
      maximum entropy and nonlinear least squares method (MEM/NLS).
AB  - PURPOSE: To assess the feasibility of using a hybrid Maximum-Entropy/Nonlinear
      Least Squares (MEM/NLS) method for analyzing the kinetics of hyperpolarized
      dynamic data with minimum a priori knowledge. THEORY AND METHODS: A continuous
      distribution of rates obtained through the Laplace inversion of the data is used
      as a constraint on the NLS fitting to derive a discrete spectrum of rates.
      Performance of the MEM/NLS algorithm was assessed through Monte Carlo simulations
      and validated by fitting the longitudinal relaxation time curves of
      hyperpolarized [1-(13) C] pyruvate acquired at 9.4 Tesla and at three different
      flip angles. The method was further used to assess the kinetics of hyperpolarized
      pyruvate-lactate exchange acquired in vitro in whole blood and to re-analyze the
      previously published in vitro reaction of hyperpolarized (15) N choline with
      choline kinase. RESULTS: The MEM/NLS method was found to be adequate for the
      kinetic characterization of hyperpolarized in vitro time-series. Additional
      insights were obtained from experimental data in blood as well as from previously
      published (15) N choline experimental data. CONCLUSION: The proposed method
      informs on the compartmental model that best approximate the biological system
      observed using hyperpolarized (13) C MR especially when the metabolic pathway
      assessed is complex or a new hyperpolarized probe is used.

PMID- 25046364
TI  - Mutation, clonal fitness and field change in epithelial carcinogenesis.
AB  - Developments in lineage tracing in mouse models have revealed how stem cells
      maintain normal squamous and glandular epithelia. Here we review recent
      quantitative studies tracing the fate of individual mutant stem cells which have
      uncovered how common oncogenic mutations alter cell behaviour, creating clones
      with a growth advantage that may persist long term. In the intestine this occurs
      by a mutant clone colonizing an entire crypt, whilst in the squamous oesophagus
      blocking differentiation creates clones that expand to colonize large areas of
      epithelium, a phenomenon known as field change. We consider the implications of
      these findings for early cancer evolution and the cancer stem cell hypothesis,
      and the prospects of targeted cancer prevention by purging mutant clones from
      normal-appearing epithelia.

PMID- 25046365
TI  - Effects of methanol on lipases: molecular, kinetic and process issues in the
      production of biodiesel.
AB  - The biotechnological production of biodiesel is based on
      transesterification/esterification reactions between a source of fatty acids and
      a short-chain alcohol, usually methanol, catalysed by enzymes belonging to the
      class known as lipases. Several lipases used in industrial processes, although
      stable in the presence of other organic solvents, are inactivated by methanol at
      or below the concentration optimal for biodiesel production, making it necessary
      to use stepwise methanol feeding or pre-treatment of the enzyme. In this review
      article we focus on what is currently know about methanol inactivation of
      lipases, a phenomenon which is not common to all lipase enzymes, with the goal of
      improving the biocatalytic process. We suggest that different mechanisms can lead
      to inactivation of different lipases, in particular substrate inhibition and
      protein unfolding. Attempts to improve the performances of methanol sensitive
      lipases by mutagenesis as well as process engineering approaches are also
      summarized. 

PMID- 25046366
TI  - Comparison of the efficacy of five adeno-associated virus vectors for transducing
      dorsal raphe nucleus cells in the mouse.
AB  - BACKGROUND: Delivery of genes to various brain regions can be accomplished using
      serotype 2 of the adeno-associated virus (AAV). Pseudotype AAV2 vectors, composed
      of the AAV2 genome packaged in the capsid of an alternative serotype, have
      increased efficiency of viral transduction. Transduction of pseudotype AAV2
      vectors depends on cell type, brain region and stage of development. The dorsal
      raphe nucleus (DRN) and median raphe provides the majority of serotonin to
      forebrain regions and are implicated in the pathology and treatment of depression
      and anxiety. Viral vector technology in combination with stereotaxic surgery in
      mice provides a means to differentiate gene function in the DRN compared to the
      median raphe nucleus. NEW METHOD: Since AAV transduction efficiency has not yet
      been characterized for the DRN, we tested if AAV2 pseudotypes are more efficient
      than a standard serotype (AAV2/2) in transducing DRN cells in adult male mice on
      a C57BL/6J background. RESULTS: Although transduction did not differ
      significantly among vectors by 15 days post-injection, pseudotype AAV2/9 and
      AAV2/rh.10 vectors achieved significantly greater transduction of the DRN than
      did AAV2/2 and AAV2/1 vectors by 30 days post-injection. Pseudotypes AAV2/1 and
      AAV2/5 tended, although not significantly, to transduce DRN cells more
      efficiently than did AAV2/2. COMPARISON WITH EXISTING METHODS: At the same titer,
      all pseudotype AAV tested tended to transduce the DRN more efficiently than
      standard AAV2/2 serotype at 30 days post-injection. CONCLUSIONS: Our results
      support the use of pseudotype AAV2/9 and AAV2/rh.10 for studying gene deletion or
      overexpression in the DRN.

PMID- 25046367
TI  - Effect of egg white and its hydrolysate on stearoyl-CoA desaturase index and fat
      accumulation in rat tissues.
AB  - We investigated the dietary effects of egg white (EW) and its hydrolysate (EWH)
      on fat metabolism in rats. Wistar rats were divided into casein, EW and EWH
      dietary groups, and fed their respective diet for 8 weeks. Dietary EW and EWH
      decreased food intake, body weight gain and fat accumulation in the carcass,
      liver, muscles and adipose tissues, but muscle weight was increased. In addition,
      dietary EW and EWH decreased stearoyl-CoA desaturase (SCD) indices and glucose-6
      phosphate dehydrogenase activity of the liver and gastrocnemius muscle. Dietary
      EW also increased the fecal excretion of triacylglycerol, cholesterol and total
      bile acids, and decreased the serum levels of triacylglycerol and leptin. The
      suppressive effects of dietary EW on food intake and body fat accumulation were
      weakened by dietary EWH. These findings indicate that EW and EWH, especially EW,
      are effective in reducing body fat accumulation by regulating hepatic and
      muscular SCD indices.

PMID- 25046368
TI  - Optimization of novel tocopheryl acetate nanoemulsions for parenteral delivery of
      curcumin for therapeutic intervention of sepsis.
AB  - OBJECTIVE: The objective of this study is to develop a nanostructured parenteral
      delivery system, laden with curcumin (CUR), for the therapeutic intervention of
      sepsis and associated pathologies. METHODS: Nanoemulsions were fabricated using
      sonication and speed homogenization. Size and zeta potential were evaluated by
      dynamic light scattering and transmission electron microscopy analysis.
      Pharmacodynamic and pharmacokinetic studies were performed on a rat model of
      lipopolysaccharide (LPS)-induced sepsis. RESULTS: The drug content of optimized
      nanoemulsion (F5) formulation (particle size 246 +/- 08 nm, polydispersity index
      (PDI) of 0.120, zeta potential of -41.1 +/- 1.2 mV) was found to be 1.25 mg/ml.
      In vitro release studies demonstrated that F5 was able to sustain the release of
      CUR for up to 24 h. Minimal hemolysis and cellular toxicity demonstrated its
      suitability for intravenous administration. Significant reduction of inflammatory
      mediator levels was mediated through enhanced uptake by in RAW 264.7 and THP-1 in
      absence/presence of LPS. Nanoemulsion resulted in an improvement of plasma
      concentration (AUCF5/AUC CUR = 8.80) and tissue distribution of CUR in rats
      leading to a reduction in LPS-induced lung and liver injury due to less
      neutrophil migration, reduced TNF-alpha levels and oxidative stress (demonstrated
      by levels of lipid peroxides as well as carbonylated proteins) as confirmed by
      histopathological studies. CONCLUSION: The findings suggest that the therapeutic
      performance (i.e., reduction in oxidative damage in tissues) of CUR can be
      enhanced by employing tocol acetate nanoemulsions (via improving pharmacokinetics
      and tissue distribution) as a platform for drug delivery in sepsis-induced organ
      injury.

PMID- 25046369
TI  - Exome sequencing as a second-tier diagnostic approach for clinically suspected
      dysferlinopathy patients.
AB  - INTRODUCTION: Autosomal recessive muscular dystrophies are heterogeneous genetic
      disorders, with 39 genes currently implicated. Genetic diagnosis using targeted
      single-gene analysis by Sanger sequencing yields negative results in 10-20% of
      samples, warranting clinical re-evaluation and time-consuming testing of
      additional genes. This applies to dysferlinopathies caused by mutations in the
      gene encoding dysferlin (DYSF), which presents mainly as limb-girdle muscular
      dystrophy (LGMD) or distal myopathy. METHODS: We evaluated exome sequencing
      associated with data filtering for selected genes as a second-tier approach for
      genetic diagnosis in a cohort of 37 patients with an initial negative result on
      targeted DYSF analysis. RESULTS: Exome sequencing allowed for establishing (16%)
      or suggesting (8%) the molecular diagnosis by implicating other known LGMD or
      distal myopathy genes or by revealing DYSF mutations previously missed using
      mutation-screening techniques with incomplete detection yields. CONCLUSIONS:
      Exome sequencing associated with data filtering constitutes an efficient second
      tier analysis for genes implicated in LGMD or distal myopathies.

PMID- 25046370
TI  - Parents' perceptions of adaptation and family life after burn injuries in
      children.
AB  - The aim of this study was to explore parents' experiences after their child's
      burn injury, focusing on how the burn had influenced family life and child
      adjustment. Six semi-structured interviews with parents of children treated at
      burn centers 2 to 7 years previously revealed the theme, "Feeling quite alone in
      striving to regain family wellbeing". Identification of difficulties perceived by
      the parents during rehabilitation and up until the present is useful when
      developing pediatric burn care and support for parents of children with burns.

PMID- 25046371
TI  - Epigenetic modification in gliomas: role of the histone methyltransferase EZH2.
AB  - INTRODUCTION: Gliomas are characterized by increased anaplasia, malignization,
      proliferation and invasion. They exhibit high resistance to standard treatment
      with combinations of radiotherapy and chemotherapy. They are currently the most
      common primary malignancy tumors in the brain that is related to a high mortality
      rate. Recently, increasing evidence suggests that EZH2 is involved in a number of
      glioma cell processes, including proliferation, apoptosis, invasion and
      angiogenesis. AREAS COVERED: In this review, we emphasize the role of EZH2 in
      gliomas. We also address that EZH2 interacting with DNA methylation mediates
      transcriptional repression of specific genes in gliomas, and the regulation of
      EZH2 by microRNAs in gliomas. EXPERT OPINION: Although the exact role of EZH2 in
      gliomas has not been fully elucidated, to understand the role of EZH2 proteins in
      epigenetic modification will provide valuable insights into the causes of
      gliomas, and pave the way to the potential future applications of EZH2 in the
      treatment of gliomas.

PMID- 25046372
TI  - Pursuit of quantum monodromy in the far-infrared and mid-infrared spectra of
      NCNCS using synchrotron radiation.
AB  - Quantum monodromy has a dramatic and defining impact on all those physical
      properties of chain-molecules that depend on a large-amplitude bending
      coordinate, including in particular the distribution of the ro-vibrational energy
      levels. As revealed by its pure rotational (a-type) spectrum [B. P. Winnewisser
      et al., Phys. Chem. Chem. Phys., 2010, 12, 8158-8189] cyanogen iso-thiocyanate,
      NCNCS, is a particularly illuminating exemplar of quantum monodromy: it clearly
      shows the distinctive monodromy-induced dislocation of the ro-vibrational energy
      level pattern for its low-lying bending mode. This dislocation centers on a
      lattice defect in the energy vs. momentum map of the ro-vibrational levels at the
      top of the barrier to linearity, and represents an example of an excited state
      quantum phase transition [D. Larese and F. Iachello, J. Mol. Struct., 2011, 1006,
      611-628]. To complete the data, so far limited to DeltaJ = +1 transitions, we
      decided to measure the high-resolution far-infrared band of the large-amplitude
      bending vibration nu7, and, if possible, mid-infrared bands. This Perspectives
      article presents our ongoing progress towards this goal, beginning with the
      description of how to predict line positions and intensities of the a- and b-type
      bands of the large amplitude bending mode using the Generalized-SemiRigid-Bender
      (GSRB) Hamiltonian for NCNCS and ab initio dipole moment functions [B. P.
      Winnewisser et al., Phys. Chem. Chem. Phys., 2010, 12, 8158-8189]. We include
      background information about synchrotron physics to clarify the advantages and
      limitations of that radiation source for our experiments. Details of the chemical
      preparation and sample handling, leading to the realization that NCNCS is 50 kJ
      mol(-1) lower in energy than its isomer S(CN)2 [Z. Kisiel et al., J. Phys. Chem.
      A, 2013, 117, 13815-13824] are included. We present the far-infrared and mid
      infrared spectrum of NCNCS obtained at the Canadian Light Source synchrotron,
      using the IFS 125HR Bruker Fourier transform spectrometer. Eight of the
      fundamental vibrational modes of NCNCS have now been observed at high resolution.
      Initial analyses of the data confirm band assignments and demonstrate the
      accuracy of the predictions. 

PMID- 25046373
TI  - Energy efficient reconcentration of diluted human urine using ion exchange
      membranes in bioelectrochemical systems.
AB  - Nutrients can be recovered from source separated human urine; however, nutrient
      reconcentration (i.e., volume reduction of collected urine) requires energy
      intensive treatment processes, making it practically difficult to utilize human
      urine. In this study, energy-efficient nutrient reconcentration was demonstrated
      using ion exchange membranes (IEMs) in a microbial electrolysis cell (MEC) where
      substrate oxidation at the MEC anode provides energy for the separation of
      nutrient ions (e.g., NH4(+), HPO4(2-)). The rate of nutrient separation was
      magnified with increasing number of IEM pairs and electric voltage application
      (Eap). Ammonia and phosphate were reconcentrated from diluted human urine by a
      factor of up to 4.5 and 3.0, respectively (Eap = 1.2 V; 3-IEM pairs). The
      concentrating factor increased with increasing degrees of volume reduction, but
      it remained stationary when the volume ratio between the diluate (urine solution
      that is diluted in the IEM stack) and concentrate (urine solution that is
      reconcentrated) was 6 or greater. The energy requirement normalized by the mass
      of nutrient reconcentrated was 6.48 MJ/kg-N (1.80 kWh/kg-N) and 117.6 MJ/kg-P
      (32.7 kWh/kg-P). In addition to nutrient separation, the examined MEC reactor
      with three IEM pairs showed 54% removal of COD (chemical oxygen demand) in 47-hr
      batch operation. The high sulfate concentration in human urine resulted in
      substantial growth of both of acetate-oxidizing and H2-oxidizing sulfate reducing
      bacteria, greatly diminishing the energy recovery and Coulombic efficiency.
      However, the high microbial activity of sulfate reducing bacteria hardly affected
      the rate of nutrient reconcentration. With the capability to reconcentrate
      nutrients at a minimal energy consumption and simultaneous COD removal, the
      examined bioelectrochemical treatment method with an IEM application has a
      potential for practical nutrient recovery and sustainable treatment of source
      separated human urine. 

PMID- 25046374
TI  - High-temperature EBPR process: the performance, analysis of PAOs and GAOs and the
      fine-scale population study of Candidatus "Accumulibacter phosphatis".
AB  - The applicability of the enhanced biological phosphorus removal (EBPR) process
      for the removal of phosphorus in warm climates is uncertain due to frequent
      reports of EBPR deterioration at temperature higher than 25  degrees C.
      Nevertheless, a recent report on a stable and efficient EBPR process at 28 
      degrees C has inspired the present study to examine the performance of EBPR at 24
      degrees C-32  degrees C, as well as the PAOs and GAOs involved, in greater
      detail. Two sequencing batch reactors (SBRs) were operated for EBPR in parallel
      at different temperatures, i.e., SBR-1 at 28  degrees C and SBR-2 first at 24 
      degrees C and subsequently at 32  degrees C. Both SBRs exhibited high phosphorus
      removal efficiencies at all three temperatures and produced effluents with
      phosphorus concentrations less than 1.0 mg/L during the steady state of reactor
      operation. Real-time quantitative polymerase chain reaction (qPCR) revealed
      Accumulibacter-PAOs comprised 64% of the total bacterial population at 24 
      degrees C, 43% at 28  degrees C and 19% at 32  degrees C. Based on fluorescent in
      situ hybridisation (FISH), the abundance of Competibacter-GAOs at both 24 
      degrees C and 28  degrees C was rather low (<10%), while it accounted for 40% of
      the total bacterial population at 32  degrees C. However, the smaller
      Accumulibacter population and larger population of Competibacter at 32  degrees C
      did not deteriorate the phosphorus removal performance. A polyphosphate kinase 1
      (ppk1)-based qPCR analysis on all studied EBPR processes detected only
      Accumulibacter clade IIF. The Accumulibacter population shown by 16S rRNA and
      ppk1 was not significantly different. This finding confirmed the existence of
      single clade IIF in the processes and the specificity of the clade IIF primer
      sets designed in this study. Habitat filtering related to temperature could have
      contributed to the presence of a unique clade. The clade IIF was hypothesised to
      be able to perform the EBPR activity at high temperatures. The clade's robustness
      most likely helps it to fit the high-temperature EBPR sludge best and allows it
      not only to outcompete other Accumulibacter clades but coexist with GAOs without
      compromising EBPR activity. 

PMID- 25046375
TI  - Transformation of acesulfame in water under natural sunlight: joint effect of
      photolysis and biodegradation.
AB  - The transformation of acesulfame in water under environmentally relevant
      conditions, including direct and indirect photolysis, biodegradation, and
      hydrolysis, was systematically evaluated. Under natural sunlight, both direct and
      indirect photolysis of acesulfame were negligible in sterilized systems at
      neutral or alkaline pH, whereas direct photolysis occurred at pH of 4 with a rate
      constant of 0.0355 d(-1) in deionized water. No significant reduction in
      acesulfame contents was found in the dark controls or in the incubation
      experiments, indicating acesulfame was resistant to hydrolysis and
      biodegradation. In unsterilized systems, photolysis was substantially enhanced,
      implying that there was a joint effect of photolysis and biodegradation or that
      the sterilization process had the secondary effect of inactivating some
      photosensitizers. The near-surface summer half-life of acesulfame in the water
      from the Haihe River was 9 d. Specific experiments revealed the involvement of
      (1)O2/(3)DOM* in acesulfame photolysis, whereas OH exhibited only a slight
      contribution in the presence of DOM or bicarbonate. As indicated by the total
      organic carbon data, no significant mineralization occurred in both sterilized
      and unsterilized systems after acesulfame was irradiated under simulated sunlight
      for 7 d, suggesting the generation of persistent intermediates. Finally, major
      degradation intermediates were analyzed, and the degradation pathways of
      acesulfame under environmentally relevant conditions were proposed for the first
      time. 

PMID- 25046376
TI  - Combination of synchrotron radiation-based Fourier transforms infrared
      microspectroscopy and confocal laser scanning microscopy to understand spatial
      heterogeneity in aquatic multispecies biofilms.
AB  - Understanding the spatial heterogeneity within environmental biofilms can provide
      an insight into compartmentalization of different functions in biofilm
      communities. We used a non-destructive and label-free method by combining
      Synchrotron Radiation-based Fourier Transform Infrared Microspectroscopy (SR
      FTIR) with Confocal Laser Scanning Microscopy (CLSM) to distinguish the spatial
      chemical changes within multispecies biofilms grown from natural storm waters in
      flow cells. Among the different surfaces tested for biofilm growth and optimal
      imaging, mylar membranes were most suited and it enabled successful spatial
      infrared imaging of natural biofilms for obtaining reliable and interpretable
      FTIR spectra. Time series analysis of biofilm growth showed that influx of water
      during biofilm growth, results in significant changes in biofilm formation. Early
      biofilms showed active nutrient acquisition and desiccation tolerance mechanisms
      corresponding with accumulation of secreted proteins. Statistical approach used
      for the evaluation of chemical spectra allowed for clustering and classification
      of various regions of the biofilm. Microheterogeneity was observed in the
      polymeric components of the biofilm matrix, including cellulose, glycocalyx and
      dextran-like molecules. Fructan and glycan-rich regions were distinguishable and
      glycocalyx was abundant in the strongly adhering peripheral regions of biofilms.
      Inner core showed coexistence of oxygen dimers and ferrihydrite that will likely
      support growth of Fe (II)-oxidising bacteria. The combined SR-FTIR
      microspectroscopy and CSLM approach for complex natural biofilms described here
      will be useful both in understanding heterogeneity of matrix components and in
      correlating functions of juxtaposed microbial species in complex natural biofilms
      with physicochemical microenvironment to which they are exposed. 

PMID- 25046377
TI  - Prediction of micropollutant elimination during ozonation of a hospital
      wastewater effluent.
AB  - Determining optimal ozone doses for organic micropollutant elimination during
      wastewater ozonation is challenged by the presence of a large number of
      structurally diverse micropollutants for varying wastewater matrice compositions.
      A chemical kinetics approach based on ozone and hydroxyl radical (.OH) rate
      constant and measurements of ozone and .OH exposures is proposed to predict the
      micropollutant elimination efficiency. To further test and validate the chemical
      kinetics approach, the elimination efficiency of 25 micropollutants present in a
      hospital wastewater effluent from a pilot-scale membrane bioreactor (MBR) were
      determined at pH 7.0 and 8.5 in bench-scale experiments with ozone alone and
      ozone combined with H2O2 as a function of DOC-normalized specific ozone doses
      (gO3/gDOC). Furthermore, ozone and .OH exposures, .OH yields, and .OH consumption
      rates were determined. Consistent eliminations as a function of gO3/gDOC were
      observed for micropollutants with similar ozone and .OH rate constants. They
      could be classified into five groups having characteristic elimination patterns.
      By increasing the pH from 7.0 to 8.5, the elimination levels increased for the
      amine-containing micropollutants due to the increased apparent second-order ozone
      rate constants while decreased for most micropollutants due to the diminished
      ozone or .OH exposures. Increased .OH quenching by effluent organic matter and
      carbonate with increasing pH was responsible for the lower .OH exposures. Upon
      H2O2 addition, the elimination levels of the micropollutants slightly increased
      at pH 7 (<8%) while decreased considerably at pH 8.5 (up to 31%). The elimination
      efficiencies of the selected micropollutants could be predicted based on their
      ozone and .OH rate constants (predicted or taken from literature) and the
      determined ozone and .OH exposures. Reasonable agreements between the measured
      and predicted elimination levels were found, demonstrating that the proposed
      chemical kinetics method can be used for a generalized prediction of
      micropollutant elimination during wastewater ozonation. Out of 67 analyzed
      micropollutants, 56 were present in the tested hospital wastewater effluent. Two
      thirds of the present micropollutants were found to be ozone-reactive and
      efficiently eliminated at low ozone doses (e.g., >80% for gO3/gDOC = 0.5).

PMID- 25046378
TI  - Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment
      contents, noncytotoxic chemistry, and nonadherent properties toward endothelial
      cells.
AB  - Polyurethane copolymers based on alpha,omega-dihydroxypropyl
      poly(dimethylsiloxane) (PDMS) with a range of soft segment contents were prepared
      by two-stage polymerization, and their microstructures, thermal,
      thermomechanical, and surface properties, as well as in vitro hemo- and
      cytocompatibility were evaluated. All utilized characterization methods confirmed
      the existence of moderately microphase separated structures with the appearance
      of some microphase mixing between segments as the PDMS (i.e., soft segment)
      content increased. Copolymers showed higher crystallinity, storage moduli,
      surface roughness, and surface free energy, but less hydrophobicity with
      decreasing PDMS content. Biocompatibility of copolymers was evaluated using an
      endothelial EA.hy926 cell line by direct contact, an extraction method and after
      pretreatment of copolymers with multicomponent protein mixture, as well as by a
      competitive protein adsorption assay. Copolymers showed no toxic effect to
      endothelial cells and all copolymers, except that with the lowest PDMS content,
      exhibited resistance to endothelial cell adhesion, suggesting their unsuitability
      for long-term biomedical devices which particularly require re
      endothelialization. All copolymers exhibited excellent resistance to fibrinogen
      adsorption and adsorbed more albumin than fibrinogen in the competitive
      adsorption assay, suggesting their good hemocompatibility. The noncytotoxic
      chemistry of these synthesized materials, combined with their nonadherent
      properties which are inhospitable to cell attachment and growth, underlie the
      need for further investigations to clarify their potential for use in short-term
      biomedical devices.

PMID- 25046379
TI  - Visceral treatment and nutritional patterns in the management of low back pain: a
      case study.

PMID- 25046380
TI  - PAC-1 and isatin derivatives are weak matrix metalloproteinase inhibitors.
AB  - BACKGROUND: Dysregulation of apoptotic cell death is observed in a large number
      of pathological conditions. As caspases are central enzymes in the regulation of
      apoptosis, a large number of procaspase-activating compounds (PAC-1 derivatives)
      and inhibitors (isatin derivatives) have been developed. Matrix
      metalloproteinases (MMPs) have been shown to have a dual role in apoptosis. Hence
      compounds that either activate or inhibit caspases should ideally not affect
      MMPs. As many PAC-1 derivatives contain a zinc chelating ortho-hydroxy N-acyl
      hydrazone moiety and isatin derivatives has two carbonyl groups on the indole
      core, it was of interest to determine to which extent these compounds can inhibit
      MMPs. METHODS: Eight PAC-1 and five isatin derivatives were docked into MMP-9 and
      MMP-14. The same compounds were synthesized, characterized, purified and tested
      as inhibitors of MMP-9 and MMP-14, using fluorescence quenched peptide and
      biological substrates. Some of the compounds were also tested for fluorescence
      quenching. RESULTS: Molecular docking suggested that the different compounds can
      bind to the MMP active sites. However, kinetic studies showed that neither of
      these compounds was a strong MMP inhibitor. IC50 values over 100MUM were obtained
      after the enzyme activities were corrected for quenching. These IC50 values are
      far above the concentrations needed to activate or inhibit the caspases.
      CONCLUSION: The use of PAC-1 and isatin derivatives against caspases should have
      little or no effect on the activity of MMPs. GENERAL SIGNIFICANCE: Activators and
      inhibitors of caspases are important potential therapeutic agents for several
      diseases such as cancer, diabetes and neurodegenerative disorders.

PMID- 25046381
TI  - Electrophysiological evaluation of cystic fibrosis conductance transmembrane
      regulator (CFTR) expression in human monocytes.
AB  - BACKGROUND: Cystic fibrosis is caused by mutations of CFTR gene, a protein kinase
      A-activated anion channel, and is associated to a persistent and excessive
      chronic lung inflammation, suggesting functional alterations of immune cells.
      Leukocytes express detectable levels of CFTR but the molecule has not been fully
      characterized in these cells. METHODS: Freshly isolated monocytes from healthy
      individuals and CF patients were assessed by protein expression, single cell
      electrophysiological and membrane depolarization assays. RESULTS: We recorded
      chloride currents by patch clamp in healthy monocytes, after the administration
      of a CFTR stimulus. Currents were sensitive to a specific blocker of the CFTR
      channel, CFTRinh-172 and were absent in CF monocytes. Next, we evaluated the
      effects of ex vivo exposure of monocytes from cystic fibrosis patients carrying
      the F508del mutation to a chemical corrector, Vertex-325. We found an increase in
      CFTR expression by confocal microscopy and a recovery of CFTR function by both
      patch clamp and single cell fluorescence analysis. CONCLUSIONS: We confirm the
      expression of functional CFTR in human monocytes and demonstrate that blood
      monocytes can represent an adequate source of primary cells to assess new
      therapies and define diagnosis of CF. GENERAL SIGNIFICANCE: Tests to evaluate
      CFTR functional abnormalities in CF disease might greatly benefit from the
      availability of a convenient source of primary cells. This electrophysiological
      study promotes the use of monocytes as a minimally invasive tool to study and
      monitor CFTR function in individual patients.

PMID- 25046382
TI  - Adaptive remodelling by FliN in the bacterial rotary motor.
AB  - Sensory adaptation in the Escherichia coli chemosensory pathway has been the
      subject of interest for decades, with investigation focusing on the receptors
      that process extracellular inputs. Recent studies demonstrate that the flagellar
      motors responsible for cell locomotion also play a role, adding or subtracting
      FliM subunits to maximise sensitivity to pathway signals. It is difficult to
      reconcile this FliM remodelling with the observation that partner FliN subunits
      are relatively static fixtures in the motor. By fusing a fluorescent protein
      internally to FliN, we show that there is in fact significant FliN remodelling.
      The kinetics and stoichiometry of FliN in steady state and in adapting motors are
      investigated and found to match the behaviour of FliM in all respects except for
      timescale where FliN rates are about 4 times slower. We notice that motor
      adaptation is slower in the presence of the fluorescent protein, indicating a
      possible source for the difference. The behaviour of FliM and FliN is consistent
      with a kinetic and stoichiometric model that contradicts the traditional view of
      a packed, rigid motor architecture. 

PMID- 25046384
TI  - A rhodium(III) complex inhibits LPS-induced nitric oxide production and
      angiogenic activity in cellulo.
AB  - Metal-containing complexes have arisen as viable alternatives to organic
      molecules as therapeutic agents. Metal complexes possess a number of advantages
      compared to conventional carbon-based compounds, such as distinct geometries,
      interesting electronic properties, variable oxidation states and the ability to
      arrange different ligands around the metal centre in a precise fashion.
      Meanwhile, nitric oxide (NO) plays key roles in the regulation of angiogenesis,
      vascular permeability and inflammation. We herein report a novel cyclometalated
      rhodium(III) complex as an inhibitor of lipopolysaccharides (LPS)-induced NO
      production in RAW264.7 macrophages. Experiments suggested that the inhibition of
      NO production in cells by complex 1 was mediated through the down-regulation of
      nuclear factor-kappaB (NF-kappaB) activity. Furthermore, complex 1 inhibited
      angiogenesis in human umbilical vein endothelial cells (HUVECs) as revealed by an
      endothelial tube formation assay. This study demonstrates that kinetically inert
      rhodium(III) complexes may be potentially developed as effective anti-angiogenic
      agents. 

PMID- 25046383
TI  - Dynactin 3D structure: implications for assembly and dynein binding.
AB  - The multisubunit protein complex, dynactin, is an essential component of the
      cytoplasmic dynein motor. High-resolution structural work on dynactin and the
      dynein/dynactin supercomplex has been limited to small subunits and recombinant
      fragments that do not report fully on either ~1MDa assembly. In the present
      study, we used negative-stain electron microscopy and image analysis based on
      random conical tilt reconstruction to obtain a three-dimensional (3D) structure
      of native vertebrate dynactin. The 35-nm-long dynactin molecule has a V-shaped
      shoulder at one end and a flattened tip at the other end, both offset relative to
      the long axis of the actin-related protein (Arp) backbone. The shoulder projects
      dramatically away from the Arp filament core in a way that cannot be appreciated
      in two-dimensional images, which has implications for the mechanism of dynein
      binding. The 3D structure allows the helical parameters of the entire Arp
      filament core, which includes the actin capping protein, CP, to be determined for
      the first time. This structure exhibits near identity to F-actin and can be well
      fitted into the dynactin envelope. Molecular fitting of modeled CP-Arp polymers
      into the envelope shows that the filament contains between 7 and 9 Arp protomers
      and is capped at both ends. In the 7 Arp model, which agrees best with measured
      Arp stoichiometry and other structural information, actin capping protein (CP) is
      not present at the distal tip of the structure, unlike what is seen in the other
      models. The 3D structure suggests a mechanism for dynactin assembly and length
      specification. 

PMID- 25046385
TI  - Introduction of water into the heme distal side by Leu65 mutations of an oxygen
      sensor, YddV, generates verdoheme and carbon monoxide, exerting the heme
      oxygenase reaction.
AB  - The globin-coupled oxygen sensor, YddV, is a heme-based oxygen sensor diguanylate
      cyclase. Oxygen binding to the heme Fe(II) complex in the N-terminal sensor
      domain of this enzyme substantially enhances its diguanylate cyclase activity
      which is conducted in the C-terminal functional domain. Leu65 is located on the
      heme distal side and is important for keeping the stability of the heme Fe(II)-O2
      complex by preventing the entry of the water molecule to the heme complex. In the
      present study, it was found that (i) Escherichia coli-overexpressed and purified
      L65N mutant of the isolated heme-bound domain of YddV (YddV-heme) contained the
      verdoheme iron complex and other modified heme complexes as determined by optical
      absorption spectroscopy and mass spectrometry; (ii) CO was generated in the
      reconstituted system composed of heme-bound L65N and NADPH:cytochrome P450
      reductase as confirmed by gas chromatography; (iii) CO generation of heme-bound
      L65N in the reconstituted system was inhibited by superoxide dismutase and
      catalase. In a concordance with the result, the reactive oxygen species increased
      the CO generation; (iv) the E. coli cells overexpressing the L65N protein of YddV
      heme also formed significant amounts of CO compared to the cells overexpressing
      the wild type protein; (v) generation of verdoheme and CO was also observed for
      other mutants at Leu65 as well, but to a lesser extent. Since Leu65 mutations are
      assumed to introduce the water molecule into the heme distal side of YddV-heme,
      it is suggested that the water molecule would significantly contribute to
      facilitating heme oxygenase reactions for the Leu65 mutants. 

PMID- 25046386
TI  - Covered self-expanding metal stents for the treatment of refractory esophageal
      nonvariceal bleeding: a case series.
AB  - INTRODUCTION: This study aimed to assess the safety and effectiveness of covered
      self-expanding metal stents for the treatment of nonvariceal esophageal bleeding
      in patients for whom routine therapies have failed. PATIENTS AND METHODS: A
      retrospective analysis was conducted on patients with esophageal bleeding in our
      hospital. Data on hemostatic effects and complications were collected from
      patients who underwent esophageal stenting. RESULTS: In total, 4 patients were
      treated with five stents. In all 4 patients, the placement of esophageal stents
      immediately stopped the ongoing bleeding. One patient experienced recurrent
      bleeding 4 days after the removal of the first stent. Hemostasis was achieved
      after the insertion of a second stent. No stent-related complications occurred
      during or after stent implantation in the other 3 patients. CONCLUSIONS: The
      implantation of a covered self-expandable metal stent is a safe and effective
      alternative to treat acute, nonvariceal esophageal bleeding after routine
      therapies have failed.

PMID- 25046387
TI  - Deer antler--a novel model for studying organ regeneration in mammals.
AB  - Deer antler is the only mammalian organ that can fully grow back once lost from
      its pedicle - the base from which it grows. Therefore, antlers probably offer the
      most pertinent model for studying organ regeneration in mammals. This paper
      reviews our current understanding of the mechanisms underlying regeneration of
      antlers, and provides insights into the possible use for human regenerative
      medicine. Based on the definition, antler renewal belongs to a special type of
      regeneration termed epimorphic. However, histological examination failed to
      detect dedifferentiation of any cell type on the pedicle stump and the formation
      of a blastema, which are hallmark features of classic epimorphic regeneration.
      Instead, antler regeneration is achieved through the recruitment, proliferation
      and differentiation of the single cell type in the pedicle periosteum (PP). The
      PP cells are the direct derivatives of cells resident in the antlerogenic
      periosteum (AP), a tissue that exists in prepubertal deer calves and can induce
      ectopic antler formation when transplanted elsewhere on the deer body. Both the
      AP and PP cells express key embryonic stem cell markers and can be induced to
      differentiate into multiple cell lineages in vitro and, therefore, they are
      termed antler stem cells, and antler regeneration is a stem cell-based epimorphic
      regeneration. Comparisons between the healing process on the stumps from an
      amputated mouse limb and early regeneration of antlers suggest that the stump of
      a mouse limb cannot regenerate because of the limited potential of periosteal
      cells in long bones to proliferate. If we can impart a greater potential of these
      periosteal cells to proliferate, we might at least be able to partially
      regenerate limbs lost from humans. Taken together, a greater understanding of the
      mechanisms that regulate the regeneration of antlers may provide a valuable
      insight to aid the field of regenerative medicine. This article is part of a
      Directed Issue entitled: Regenerative Medicine: the challenge of translation. 

PMID- 25046388
TI  - Repeated measurements of motor activity in rats in long-term toxicity studies.
AB  - INTRODUCTION: In the light of 3R (replace, reduce, refine) principles in animal
      experimentation and increased focus on delayed effects of treatment on central
      nervous system, the incorporation of behavioural tests into standard toxicology
      studies as a complement or substitution of a stand-alone safety pharmacology
      study appears very attractive, but poses some challenges. In the present study,
      we evaluated the results of an open field test (standard part of the behavioural
      test batte- ries) incorporated into the 3-month regulatory toxicology study.
      METHODS: The study was performed in two rat strains most commonly used in
      toxicology studies (Wistar and Sprague Dawley (SprD)). Open field test was
      performed according to the standard protocol for stand-alone behavioural test
      (modified Irwin test) before the start of treat- ment (Day-7, "naive" animals),
      on Day 2, inWeek 6 and inWeek 13 of treatment with saline. RESULTS AND
      DISCUSSION: There was no overall difference between strains, and only minor
      differences were detected at the individual time points. With regard to time
      effect, the average values for most of the parameters were comparable throughout
      the study but individual variability in the performance in the arena was
      increased at repeated measurements compared to the start. In conclusion,
      performance in the open field arena did not differ principally between Wistar and
      SprD rats of both genders. However, individual variability in the behaviour in
      the open field arena increased with time. This has clear implications for
      deciding the appropriate group size for this type of study and has to be taken
      into account in the design of a toxicology study with integrated safety
      pharmacology endpoints.

PMID- 25046389
TI  - Purification, characterization and immunoreactivity of beta'-component, a major
      allergen from the roe of large yellow croaker (Pseudosciaena crocea).
AB  - Fish roe, a nutritious food, is favored by consumers, but has also been confirmed
      to be allergenic in salmonid fish. However, little information is available in
      other fish species. To determine the allergen in the roe of large yellow croaker
      (Pseudosciaena crocea), crude extracts were incubated with sera of allergic
      patients. The major allergen was purified by column chromatography methods,
      revealing a single band with 16 kDa and was confirmed as beta'-component (beta'
      c) by mass spectrometry. The results of physicochemical characterization showed
      that beta'-c was a glycoprotein and was relatively stable following thermal or
      acid/alkali treatment. Furthermore, beta'-c was easily degraded by pepsin, but
      was resistant to trypsin and alpha-chymotrypsin. After treatment with different
      processing methods, including Maillard reaction (MR), ultraviolet radiation
      (UVR), ultrasound-heat (UH), and retorting (RT), the IgG-binding activity of
      beta'-c decreased obviously by MR, but decreased slightly by UVR and UH. Cross
      immunoreactivity results of the allergens in the roes of different species
      revealed that beta'-c was a specific allergen in teleostean, and the cross
      immunoreactivity between the roe of large yellow croaker and other kinds of fish
      roe was relatively strong.

PMID- 25046390
TI  - Direct medical costs and resource use for treating central and branch retinal
      vein occlusion in commercially insured working-age and Medicare populations.
AB  - PURPOSE: To quantify the burden of illness for incident branch retinal vein
      occlusion (BRVO) and central retinal vein occlusion (CRVO) in a commercially
      insured working-age (commercial) and Medicare US population. METHODS:
      Retrospective cohort analysis of health care claims from 2003 through 2008 from
      commercial and Medicare patients with >=2 outpatient diagnoses for BRVO or CRVO.
      The index date was the first retinal vein occlusion diagnosis. Patients with
      medical and pharmacy benefits were followed >=1 year preindex and then between 1
      year and 3 years postindex. Incidence and prevalence of retinal vein occlusion
      was determined. Burden of illness was compared with matched control subjects
      without retinal vein occlusion. RESULTS: The commercial sample comprised 1,188
      CRVO and 2,252 BRVO cases, whereas the Medicare sample had 2,739 CRVO and 4,573
      BRVO cases. Adjusted ratio of case-to-control, all-cause expenditures for
      commercial patients at 1 year and 3 years postindex were 1.88 and 1.68,
      respectively, for BRVO and 1.42 and 1.36, respectively, for CRVO. For Medicare
      patients, these were 1.29 and 1.13, respectively, for BRVO and 1.23 and 1.14,
      respectively, for CRVO. All comparisons were significant (P < 0.001). CONCLUSION:
      Health care utilization and expenditures for commercially insured working-age and
      Medicare patients with BRVO or CRVO were significantly greater than those for
      control subjects. Retinal vein occlusion development may be a marker for the
      increased severity of systemic vascular disease.

PMID- 25046391
TI  - Combined pars plana vitrectomy and pars plana Baerveldt tube placement in eyes
      with neovascular glaucoma.
AB  - PURPOSE: To describe characteristics and outcomes of combined pars plana
      vitrectomy and Baerveldt tube insertion procedure from 2005 to 2010 in eyes with
      neovascular glaucoma. METHODS: Seventy-nine patients (89 eyes) with >=2 months of
      follow-up were included. Outcome measures were visual acuity, intraocular
      pressure (IOP), number of glaucoma medications, and complications. Changes in
      mean logMAR visual acuity, IOP, and glaucoma medications were compared by a two
      tailed t-test. RESULTS: Mean patient age was 69.0 years. Forty-three (54%) were
      male. Mean follow-up time was 19.9 months. Most common causes of neovascular
      glaucoma was diabetes (n = 63 [71%]) and central retinal vein occlusion (n = 21
      [24%]). Eighty-six eyes (97%) underwent a 250 mm Baerveldt drainage device and 3
      (3.4%) a 350 mm Baerveldt. Forty-five (51%) 20-gauge, 12 (13%) 23-gauge, and 32
      (36%) 25-gauge pars plana vitrectomies were performed. Fifty-two eyes (58%)
      preoperatively and 23 (33%) postoperatively received intraocular injections for
      rubeosis and macular edema. Mean +/- standard deviation logMAR visual acuity at
      18-, 24-, 36-, and 48-month follow-up time points was significantly better than
      preoperative vision (P < 0.05). Preoperative versus final IOP and number of
      glaucoma medications were significantly decreased (P < 0.05). Fourteen eyes (16%)
      had a final visual acuity of no light perception. Most common complications
      included transient ocular hypertension (n = 82 [92%]), transient hypotony (n = 20
      [22%]), hyphema (n = 19 [21%]), corneal edema (n = 17 [19%]), and vitreous
      hemorrhage (n = 14 [16%]). The frequency of transient hypotony, vitreous
      hemorrhage, and rubeosis was significantly (P < 0.05) higher in 20-gauge versus
      23-/25-gauge pars plana vitrectomy eyes. Nine eyes (10%) required return to the
      operating room after combined procedure, including 4 eyes (4.5%) for retinal
      detachment and 3 (3.4%) for high IOP due to tube occlusion. Three eyes (3.4%)
      developed endophthalmitis and 2 (2.2%) progressed to being pre/phthisical (none
      were enucleated). CONCLUSION: Combined pars plana vitrectomy and Baerveldt
      glaucoma shunt may be a useful procedure in reducing IOP and number of glaucoma
      medications in eyes with neovascular glaucoma along with stabilizing visual
      acuity in a majority of these eyes. Further studies are warranted to verify and
      expand on these findings.

PMID- 25046392
TI  - Geometry, penetration force, and cutting profile of different 23-gauge trocars
      systems for pars plana vitrectomy.
AB  - BACKGROUND: To investigate the geometry, penetration force, and cutting profile
      of 23-gauge trocar systems for pars plana vitrectomy based on their grinding
      methods in a standardized laboratory setting. METHODS: In this experimental
      study, Eleven different commercially available 23-gauge sclerotomy trocar systems
      were divided into 4 groups according to their needle grinding and deburring:
      "back" bevel, "spear" bevel, "lancet" bevel, and "spatula" bevel. The normative
      geometrical data of the trocar systems were systematically analyzed according to
      nomenclature ISO 7864 and ISO 9626. Force to penetrate a 0.4-mm thick
      polyurethane foil was measured by a Penetrometer, when the trocar needle was
      piercing, cutting, and sliding through the foil at different defined loading
      phases and plotted as a load-displacement diagram. Magnified images of the
      consecutive cut were taken under a microscope after the entire penetration
      through the foil. Three physicians used all trocar systems in a masked fashion on
      human sclera to evaluate the manual penetration force in 30 degrees  and 90
      degrees . RESULTS: The mean outer diameter of the trocar systems was 0.630 +/-
      0.009 mm, and the mean outer diameter of the trocars was 0.750 +/- 0.013 mm. The
      mean point length was 3.11 +/- 0.49 mm, and the mean length of the bevel was 1.46
      +/- 0.23 mm. The primary bevel angle was 10.75 +/- 0.41 degrees , and the
      secondary bevel angle was 65.9 +/- 42.56 degrees . The piercing forces of the
      back bevel and spear-pointed trocars/needles were at the same level (0.087 +/-
      0.028 N). The lancet-pointed needle had remarkable low piercing and cutting
      forces with 0.41 N (range, 0.35-0.47 N). The spatula bevel tip showed the highest
      penetration piercing force with 1.6 N (range, 1.59-1.73 N). The back bevel
      systems induced frequently triangular-shaped incisions, with two nearly
      rectangular cuts of short length. The spear bevels produced a regular
      characteristic linear cut. Especially, the lancet blade created straight cut with
      a linear wound apposition. Spatula trocar systems caused usually an arched
      accurate incision. The manual force to penetrate the human sclera in an angled
      and rectangular angle appeared in the surgeons hand lower with a back bevel,
      lancet, or spear tip, whereas higher with spatula bevel systems. CONCLUSION:
      Lancet and back bevel systems show less penetration force of inner needles than
      the spatula systems. The results of the penetration force experiments correlated
      well with the manual force on sclera.

PMID- 25046393
TI  - Idiopathic internal limiting membrane detachment.

PMID- 25046394
TI  - Collateral vessel presence in branch and central retinal vein occlusions and
      their impact on visual acuity and anatomical gains: a retrospective analysis.
AB  - PURPOSE: To evaluate the incidence of collateral vessel formation and to
      determine their impact on best-corrected visual acuity and central foveal
      thickness in patients with branch or central retinal vein occlusion (BRVO, CRVO)
      receiving 0.3 mg or 0.5 mg of ranibizumab, or sham. METHODS: This retrospective
      analysis was performed in patients with macular edema secondary to retinal vein
      occlusion who received 6 monthly intravitreal injections of ranibizumab (0.3 mg
      or 0.5 mg), or sham, followed by 6 months of as-needed treatment. Collateral
      vessel presence, change from baseline best-corrected visual acuity, and change
      from baseline central foveal thickness were assessed at baseline and months 3, 6,
      9, and 12. RESULTS: At month 12, 19.6% of BRVO patients receiving sham/0.5 mg and
      16.7% receiving ranibizumab (0.3 mg and 0.5 mg pooled) manifested collaterals at
      the disk, whereas 48.2% and 47.2% displayed collaterals within the retina,
      respectively. In CRVO patients, 57.9% and 59.2% of all groups manifested
      collaterals on the disk, respectively, whereas 12.1% and 15.1% displayed
      collaterals within the retina. Mean best-corrected visual acuity gain in
      ranibizumab-treated BRVO and CRVO patients was similar, irrespective of
      collaterals within the retina ( BRVO: P > 0.05; CRVO: P > 0.05). CONCLUSION: The
      location of collaterals differed between retinal vein occlusion subtypes and
      ranibizumab treatment did not affect collateral vessel incidence. The presence of
      collaterals did not seem to impact best-corrected visual acuity gains at month 12
      in both BRVO and CRVO patients receiving ranibizumab, whereas generally greater
      central foveal thickness reductions were observed with presence of collaterals in
      BRVO patients.

PMID- 25046395
TI  - Retinal pigment epithelium findings in patients with albinism using wide-field
      polarization-sensitive optical coherence tomography.
AB  - PURPOSE: To investigate pigmentation characteristics of the retinal pigment
      epithelium (RPE) in patients with albinism using wide-field polarization
      sensitive optical coherence tomography compared with intensity-based spectral
      domain optical coherence tomography and fundus autofluorescence imaging. METHODS:
      Five patients (10 eyes) with previously genetically diagnosed albinism and 5
      healthy control subjects (10 eyes) were imaged by a wide-field polarization
      sensitive optical coherence tomography system (scan angle: 40 * 40 degrees  on
      the retina), sensitive to melanin contained in the RPE, based on the polarization
      state of backscattered light. Conventional intensity-based spectral domain
      optical coherence tomography and fundus autofluorescence examinations were
      performed. Retinal pigment epithelium-pigmentation was analyzed qualitatively and
      quantitatively based on depolarization assessed by polarization-sensitive optical
      coherence tomography. RESULTS: This study revealed strong evidence of
      polarization-sensitive optical coherence tomography to specifically image melanin
      in the RPE. Depolarization of light backscattered by the RPE in patients with
      albinism was reduced compared with normal subjects. Heterogeneous RPE-specific
      depolarization characteristics were observed in patients with albinism. Reduction
      of depolarization observed in the light backscattered by the RPE in patients with
      albinism corresponds to expected decrease of RPE pigmentation. The degree of
      depigmentation of the RPE is possibly associated with visual acuity. Findings
      suggest that different albinism genotypes result in heterogeneous levels of RPE
      pigmentation. CONCLUSION: Polarization-sensitive optical coherence tomography
      showed a heterogeneous appearance of RPE pigmentation in patients with albinism
      depending on different genotypes.

PMID- 25046396
TI  - Optic coherence tomography of foveal hemorrhage associated with chronic
      myelogenous leukemia.

PMID- 25046397
TI  - Short-term efficacy of intravitreal aflibercept in treatment-naive patients with
      polypoidal choroidal vasculopathy.
AB  - PURPOSE: To evaluate the functional and morphologic outcomes of patients with
      polypoidal choroidal vasculopathy who underwent intravitreal aflibercept
      treatment. METHODS: We prospectively studied all the treatment-naive patients
      with polypoidal choroidal vasculopathy who were scheduled to undergo intravitreal
      aflibercept between February 2013 and July 2013. The best-corrected visual acuity
      was compared before treatment and at 6 months after the initial treatment.
      Changes in the central foveal thickness, choroidal thickness, presence/absence of
      subretinal fluid, fibrin, pigment epithelial detachment, and subretinal
      hemorrhage were also evaluated. The regression of the polyps was assessed using
      indocyanine green angiography. RESULTS: A total of 16 patients were included in
      this study. A significantly better best-corrected visual acuity at 6 months was
      seen, compared with that at baseline (P = 0.041). The mean central foveal
      thickness significantly decreased from 417 +/- 127 MUm to 187 +/- 50 MUm (P <
      0.001). The mean choroidal thickness also significantly decreased from 250 +/- 63
      MUm to 217 +/- 64 MUm (P = 0.011). Overall, a complete resolution was obtained in
      93.3% (14/15) of the cases with subretinal fluid, 75.0% (3/4) of the cases with
      fibrin, and 88.9% (8/9) of the cases with subretinal hemorrhage. Fifty-six
      percent (5/9) of the cases with pigment epithelial detachment obtained a complete
      improvement, whereas 33.3% (3/9) exhibited a partial decrease. The rate of polyp
      regression was 75.0% (12/16). CONCLUSION: Intravitreal aflibercept was well
      tolerated and had improved the vision of treatment-naive patients with polypoidal
      choroidal vasculopathy when it was evaluated at short-term follow-up
      examinations. Intravitreal aflibercept might be associated with a high
      possibility of achieving involution of polyps and reducing exudative findings.

PMID- 25046398
TI  - PACHYCHOROID: an inherited condition?
AB  - PURPOSE: Thick choroid (pachychoroid) is associated with central serous
      chorioretinopathy (CSC), but whether pachychoroid is inherited is unknown.
      METHODS: In a prospective observational study, first- or second-degree relatives
      (16 individuals) of 5 patients with CSC had refraction and visual acuity
      measurement, fundus examination, nonmydriatic photography, and autofluorescence
      photography. Eyes were graded using the following criteria: 0: normal fundus and
      autofluorescence photography, 1: focal retinal pigment epithelium
      hyperfluorescence and/or hypofluorescence and/or retinal pigment epithelial
      detachment, 2: CSC or diffuse retinal epitheliopathy. Choroid thickness was
      measured by enhanced depth imaging mode on optical coherence tomography. RESULTS:
      Considering 395 MUm as the threshold limit for normal subfoveal choroidal
      thickness, 50% of the eyes from relatives had a thick choroid. Nine eyes of Grade
      0 (28%) with an isolated pachychoroid would thus have been considered normal, if
      choroidal thickness was not included as a screening sign predisposing for CSC.
      CONCLUSION: Our observation suggests that pachychoroid could be an inherited
      condition with potentially a dominant transmission mode. Its inclusion in the
      phenotype of CSC for genetic studies should be considered.

PMID- 25046399
TI  - Development of an IFN-gamma ELISpot assay to assess varicella-zoster virus
      specific cell-mediated immunity following umbilical cord blood transplantation.
AB  - Varicella zoster virus (VZV) is a significant cause of morbidity and mortality
      following umbilical cord blood transplantation (UCBT). For this reason,
      antiherpetic prophylaxis is administrated systematically to pediatric UCBT
      recipients to prevent complications associated with VZV infection, but there is
      no strong, evidence based consensus that defines its optimal duration. Because T
      cell mediated immunity is responsible for the control of VZV infection, assessing
      the reconstitution of VZV specific T cell responses following UCBT could provide
      indications as to whether prophylaxis should be maintained or can be
      discontinued. To this end, a VZV specific gamma interferon (IFN-gamma) enzyme
      linked immunospot (ELISpot) assay was developed to characterize IFN-gamma
      production by T lymphocytes in response to in vitro stimulation with irradiated
      live attenuated VZV vaccine. This assay provides a rapid, reproducible and
      sensitive measurement of VZV specific cell mediated immunity suitable for
      monitoring the reconstitution of VZV specific immunity in a clinical setting and
      assessing immune responsiveness to VZV antigens.   

PMID- 25046400
TI  - Evaluation of the progression rate of atrophy lesions in punctate inner
      choroidopathy (PIC) based on autofluorescence analysis.
AB  - PURPOSE: To investigate the autofluorescence (AF) characteristics of punctate
      inner choroidopathy (PIC) and to evaluate the progression rate of retinal pigment
      epithelium (RPE) atrophy lesions in PIC using confocal scanning laser
      ophthalmoscopy. METHODS: Twenty-two eyes of 14 PIC cases and 21 eyes of 21 non
      proliferative diabetic retinopathy (NPDR) cases which received retinal
      coagulation as a control group were enrolled in this study. Enhanced depth
      imaging optical coherence tomography (EDI-OCT) and AF were recorded from all
      patients at 18 months follow-up. The RPE atrophy areas of PIC and laser scars in
      NPDR were analyzed using the Region Finder software of the Heidelberg Eye
      Explorer. This software allows direct export of AF images from the database and
      semi-automated detection of atrophic areas by shadow correction, vessel
      detection, and selection of seed points. RESULTS: At baseline, both
      hyperfluorescence and hypofluorescence were observed in the lesions of PIC eyes
      with a focal elevation of RPE and corresponding disruption of the ellipsoid
      region of the inner segment ellipsoid zone (EZ). In contrast, hypo-AF was
      detected when there was a lack of RPE. The mean progression rate of RPE atrophy
      in PIC and NPDR were 3.735 mm(2)/year (0.056-0.545) and 0.127 mm(2)/year (0.015
      0.466), respectively. Compared with the atrophy area in the last visit, the
      progression rate in PIC was significantly greater than that in NPDR (Z=5.615,
      P<0.0001). CONCLUSIONS: The results of AF reflect the status of PIC and the
      progression rate of RPE atrophy in PIC, which can be used to predict the progress
      of PIC noninvasively.

PMID- 25046401
TI  - The noninvasive predictive approach for choroidal vascular diffuse
      hyperpermeability in central serous chorioretinopathy: near-infrared reflectance
      and enhanced depth imaging.
AB  - PURPOSE: To investigate near-infrared reflectance (NIR) findings in central
      serous chorioretinopathy (CSCR) and to predict the choroidal vascular diffuse
      hyperpermeability (CVDHP) by NIR and enhanced depth imaging spectral-domain
      optical coherence tomography (EDI SD-OCT) noninvasively. METHODS: Retrospective
      analysis of 52 eyes of 50 CSCR patients with serous macular detachment. All
      patients received NIR, indocyanine green angiography (ICGA), and EDI SD-OCT. NIR
      patterns (irregular, defected, masked and enhanced), double layer sign (DLS) in
      EDI SD-OCT and CVDHP in ICGA were evaluated. In addition, we measured the length
      of photoreceptor outer segment (LPOS), and subfoveal choroidal thickness (SFCT)
      by Heidelberg eye explorer software. Moreover, the integrity of the junction of
      inner segment and outer segment of photoreceptor (IS/OS) was recorded. RESULTS:
      42 (80.8%) eyes were identified with CVDHP, and 10 (19.2%) eyes appeared
      disrupted IS/OS. Irregular NIR pattern was found in 48 (92.3%) eyes, as well as
      DLS was observed in 37 (71.2%) eyes. In addition, irregular NIR pattern, together
      with DLS had a significant positive correlation with the occurrence of CVDHP
      (r=0.605, p<0.0001). Moreover, in IS/OS preserved eyes, there was also a
      significant positive relationship between CVDHP and LPOS (r=0.599, p<0.0001). In
      contrast, SFCT only demonstrated a moderate positive relationship with CVDHP in
      this group (r=0.441, p=0.013<0.05). CONCLUSIONS: Irregular NIR pattern, DLS and
      LPOS are qualitative and quantitative indexes for CVDHP. Our study suggests that
      NIR can detect CVDHP effectively and noninvasively. The combined detection of NIR
      and EDI SD-OCT is a predictive approach for CSCR patients, as a supplement of
      ICGA.

PMID- 25046402
TI  - Additive benefits of autonomy support and enhanced expectancies for motor
      learning.
AB  - Two factors that have been shown to facilitate motor learning are autonomy
      support (AS) and enhanced expectancies (EE) for performance. We examined the
      individual and combined influences of these factors. In a 2 * 2 design,
      participants learning a novel motor skill (throwing with the non-dominant arm)
      were or were not provided a choice (AS) about the ball color on each of 6 10
      trial blocks during practice, and were or were not given bogus positive social
      comparative feedback (EE). This resulted in four groups: AS/EE, AS, EE, and C
      (control). One day after the practice phase, participants completed 10 retention
      and 10 transfer trials. The distance to the target--a bull's eye with a 1m radius
      and 10 concentric circles--was 7.5m during practice and retention, and 8.5m
      during transfer. Autonomy support and enhanced expectancies had additive
      advantages for learning, with both main effects being significant for retention
      and transfer. On both tests, the AS/EE group showed the greatest throwing
      accuracy. Also, the accuracy scores of the AS and EE groups were higher than
      those of the C group. Furthermore, self-efficacy measured after practice and
      before retention and transfer was increased by both AS and EE. Thus, supporting
      learners' need for autonomy by given them a small choice--even though it was not
      directly related to task performance--and enhancing their performance
      expectancies appeared to independently influence learning.

PMID- 25046403
TI  - Enhancing patient engagement and blood pressure management for renal transplant
      recipients via home electronic monitoring and web-enabled collaborative care.
AB  - BACKGROUND: Effective management of hypertension in chronic kidney disease and
      renal transplantation is a clinical priority and has societal implications in
      terms of preserving and optimizing the value of scarce organs. However,
      hypertension is optimally managed in only 37% of people with chronic kidney
      disease, and poor control can contribute to premature graft loss in renal
      transplant recipients. This article describes a telehealth system that
      incorporates home electronic blood pressure (BP) monitoring and uploading to a
      patient portal coupled with a Web-based dashboard that enables clinical
      pharmacist collaborative care in a renal transplant clinic. MATERIALS AND
      METHODS: The telehealth system was developed and implemented as a quality
      improvement initiative in a renal transplant clinic in a large, 700-bed, urban
      hospital with the aim of improving BP in posttransplant patients. A convenience
      sample of 66 posttransplant patients was recruited by the clinical pharmacist
      from consecutive referrals to the Transplant Clinic. RESULTS: Preliminary results
      show statistically significant reductions in average systolic and diastolic BP of
      6.0 mm Hg and 3.0 mm Hg, respectively, at 30 days after enrollment. Two case
      reports describe the instrumental role of home BP monitoring in the context of
      medication therapy management. CONCLUSIONS: Optimizing BP control for both pre-
      and post-renal transplant patients is likely to benefit society in terms of
      preserving scarce resources and reducing healthcare costs due to premature graft
      failure. Connected health systems hold great promise for supporting team-based
      care and improved health outcomes.

PMID- 25046404
TI  - Facile and fast synthesis of graphene oxide nanosheets via bath ultrasonic
      irradiation.
AB  - For the first time, this work reports a facile sonochemical route in the
      synthesis of graphene oxide nanosheets (GO) via oxidation of graphite (G). The
      synthesis of GO was carried out in a fast way under ultrasonic bath irradiation
      (GO-U). In comparison, the synthesis of GO via classical method (GO-C) was done
      under the same conditions as ultrasonic method. The products were completely
      different and the oxidation did not happen the same as way as ultrasonic method.
      Furthermore, GO was synthesized based on classical approach that most commonly
      used (GO-C'), not under the same conditions as ultrasonic method. The GO sheets
      were characterized using UV-Vis, Fourier transform infrared (FT-IR), X-ray
      diffraction (XRD), transmission electron microscope (TEM), thermal gravimetry
      (TG), and Raman spectroscopy techniques. The XRD confirms that the spaces between
      GO-U and GO-C' sheets were higher than graphite. Also, XRD indicated that the GO
      U has fewer sheets rather than GO-C'. The TEM observations were confirmed the
      synthesis of nanosheets. The UV-Vis results were shown the absorption peaks at
      230nm for GO-U and GO-C', at 245nm for GO-C, and at 255nm for G. The blue shift
      in GO-U with respect to G and GO-C can be interpreted based on the higher
      character of sp(3)/sp(2) in GO-U than G and GO-C. The FT-IR presents the
      oxygenated functional groups on graphene oxide sheets. A reduction in size of the
      in-plane sp(2) domains was observed by Raman spectrum. The BET analysis for G, GO
      U and GO-C' confirmed that GO-U has a highest specific surface area among all the
      samples. Therefore, the ultrasonic bath method even with low intensity has a
      fundamental role in the synthesis of graphene oxide nanosheets and it is
      relatively fast, simple, cost-effective and efficient as compared to the
      classical method. 

PMID- 25046405
TI  - Wide-field multiplexed imaging of EGFR-targeted cancers using topical application
      of NIR SERS nanoprobes.
AB  - AIM: As the possibilities of molecular imaging in personalized medicine evolve
      rapidly, the optical advantages of extremely narrow and intense spectral bands
      makes surface-enhanced Raman scattering (SERS) an appealing candidate for
      multiplexed recognition of targeted biomarkers over other optical imaging
      modalities. MATERIALS & METHODS: In this proof-of-concept study, we report wide
      field Raman detection of lung cancer using multimodal SERS nanoprobes specific to
      the EGF receptor family, both in vitro and in vivo. RESULTS: For the first time,
      we demonstrate wide-field multiplexed Raman imaging for cancer detection in vivo
      after topical application of a 'cocktail' of SERS nanoprobes. CONCLUSION: This
      advancement represents a key step towards sensitive wide-field Raman endoscopic
      imaging of multiple biomarkers for early and accurate diagnosis of EGF receptor
      expressing tumors of different internal organs.

PMID- 25046406
TI  - Stimuli-responsive photoacoustic nanoswitch for in vivo sensing applications.
AB  - Photoacoustic imaging provides high-resolution images at depths beyond the
      optical diffusion limit. To broaden its utility, there is need for molecular
      sensors capable of detecting environmental stimuli through alterations in
      photoacoustic signal. Photosynthetic organisms have evolved ingenious strategies
      to optimize light absorption through nanoscale ordered dye aggregation. Here, we
      use this concept to synthesize a stimuli-responsive nanoswitch with a large
      optical absorbance and sensing capabilities. Ordered dye aggregation between
      light-harvesting porphyrins was achieved through intercalation within
      thermoresponsive nanovesicles. This causes an absorbance red-shift of 74 nm and a
      2.7-fold increase in absorptivity of the Qy-band, with concomitant changes in its
      photoacoustic spectrum. This spectral feature can be reversibly switched by
      exceeding a temperature threshold. Using this thermochromic property, we
      noninvasively determined a localized temperature change in vivo, relevant for
      monitoring thermal therapies of solid tumors. Similar strategies may be applied
      alongside photoacoustic imaging, to detect other stimuli such as pH and enzymatic
      activity.

PMID- 25046407
TI  - Introducing a new stratospheric dust-collecting system with potential use for
      upper atmospheric microbiology investigations.
AB  - The stratosphere is a known host to terrestrial microbes of most major biological
      lineages, but it is also host to incoming meteoric dust. Our goal is to (1)
      introduce DUSTER (Dust in the Upper Stratosphere Tracking Experiment and
      Retrieval), an active collector for the nondestructive collection of nano- to
      micrometer particles in the stratosphere between 30 and 40 km altitude, and (2)
      demonstrate that even a single particle can be collected free of resident
      atmospheric and laboratory contaminant particles. DUSTER improves the pervasive
      and persistent contamination problem in the field of aerobiology research. Here,
      we demonstrate the collector's advances by the identification of a (terrestrial)
      spore particle found among a population of nanometer-scale inorganic meteoric
      particles. This was possible because the size, shape, morphology, and chemical
      composition of each particle can be determined while still on the collector
      surface. Particles can be removed from DUSTER for specific laboratory analyses.
      So far, DUSTER has not been fitted for aerobiological purposes; that is, no
      attempts were made to sterilize the collector other than with isopropyl alcohol.
      Its design and laboratory protocols, however, allow adjustments to dedicated
      aerobiological sampling opportunities.

PMID- 25046408
TI  - T-cell therapy against cancer mutations.

PMID- 25046409
TI  - 75 years of contemporary intramedullary nailing.

PMID- 25046410
TI  - Intramedullary nailing of the femoral shaft: a prospective, randomized study.
AB  - We conducted a prospective, randomized study on 84 consecutive patients with 88
      acute, traumatic femoral shaft fractures using 32 Grosse-Kempf nails, 29 Russell
      Taylor nails, and 27 Synthes nails. Although total operative times and proximal
      and distal locking times were similar for the three groups, the procedure was
      faster with the Grosse-Kempf nail. Three proximal fractures could not be locked
      with the Synthes nail. At first follow-up, we found no significant difference in
      terms of pain, limp, range of motion, or time to union; however, we removed fewer
      Synthes nails to resolve patient complaints of pain. Three delayed unions were
      attributed to fracture distraction. We conclude that all three nails are suitable
      for the treatment of almost all femoral shaft fractures. A careful analysis of
      intraoperative technique and instrumentation indicates that all three nails can
      be used safely and easily once experience is gained. Clinical outcome is similar
      regardless of the nail chosen.

PMID- 25046411
TI  - Retrograde reamed femoral nailing.
AB  - Closed, reamed, antegrade nailing remains the standard of care for femoral shaft
      fractures. This technique however, may be less attractive in the management of
      femoral shaft fractures associated with (a) ipsilateral acetabular, pelvis, or
      femoral neck fractures; (b) poly trauma requiring multiple simultaneous surgical
      procedures; and (c) pregnancy. We now report on our experience with the
      retrograde femoral nailing as a treatment option in these situations. Between
      4/88 and 10/90, 29 retrograde femoral nailing in 24 patients were attempted.
      Average age was 29.3 (16-74) years. Five fractures were open. Fracture location
      was isthmal in 14 and infraisthmal in 15. The comminution was classified
      according to Winquist and Hansen: I(10), II(7), III(7), and IV(5). Nailing was
      possible in 28/29 cases. Insertion was made through an extraarticular medial
      condylar portal. Nail diameter ranged from 10 to 13 mm. An AO Universal Femoral
      Nail was used in the first 11 cases; all subsequent fractures were stabilized
      using an AO Universal Tibial Nail because its design appeared better suited to
      this technique. Follow-up was possible for 25 fractures in 21 patients and
      averaged 16.0 (range, 11-27); months 23/25 (92%) fractures healed within 12
      weeks. No case was associated with an infection, loss of reduction, or nail
      failure. Knee flexion averaged 122 degrees ; only two knees had an extensor lag
      of >5 degrees . Intraoperative complications included three cases of crack
      propagation at the insertion site, and four infraisthmal malreductions (two
      valgus, two flexion). Based on these results, we feel that retrograde reamed
      femoral nailing is a suitable alternative to antegrade nailing and should be
      considered in situations where proximal access is neither possible nor desirable.

PMID- 25046412
TI  - Unstable pertrochanteric femoral fractures.
AB  - BACKGROUND: Fractures in the trochanteric region of the femur are classified as
      AO/OTA 31-A, as they are extracapsular (). This report analyzes the relatively
      rare 31-A3 fracture, which has also been referred to as an "intertrochanteric
      femur fracture with subtrochanteric extension," "reverse obliquity
      intertrochanteric femur fracture," "unstable intertrochanteric femur fracture,"
      or a "subtrochanteric femur fracture." The A3 fracture is characterized by having
      a fracture line exiting the lateral femoral cortex distal to the vastus ridge.
      Possible fixation constructs include compression hip screws, intramedullary hip
      screws, trochanteric intramedullary nails, cephalomedullary antegrade
      intramedullary nails, and 95 degrees  plates. Most reports investigating 31-A
      fractures do not describe the 31-A3 fracture. For this analysis, only reports
      clearly indicating that the fracture treated was a 31-A3 were included. It should
      be understood that this approach therefore excludes reports on generic
      "subtrochanteric fractures" or "intertrochanteric fractures," some of which may
      have been 31-A3 fractures. OBJECTIVE: To determine the effect of fixation
      technique for the AO/OTA 31-A3 fracture on rates of union, infection, risk of
      reoperation, and functional outcomes.

PMID- 25046413
TI  - Semiextended intramedullary nailing of the tibia using a suprapatellar approach:
      radiographic results and clinical outcomes at a minimum of 12 months follow-up.
AB  - OBJECTIVE: To evaluate the clinical and radiographic results associated with the
      use of a percutaneous suprapatellar (SP) portal and accompanying instrumentation
      for tibial intramedullary nail (IMN) insertion using a semiextended approach.
      DESIGN: Prospective, nonrandomized, nonconsecutive study. SETTING: Level 1 trauma
      center. PATIENTS AND METHODS: From June 2007 to January 2011, 56 fractures (55
      patients) underwent intramedullary nailing of a tibia fracture with a
      semiextended approach through a SP portal. Radiographic and clinical follow-up
      examinations were performed at a minimum of 1 year after the index procedure.
      Measurements included bone healing, tibial alignment, knee range of motion, pain
      drawings, pain scoring (visual analogue scale), functional outcome (Lysholm and
      SF-36 scoring), evaluation of prenail and postnail insertion arthroscopic images
      of the patella-femoral (PF) joint (subgroup of study patients), and 1-year follow
      up magnetic resonance imaging (MRI) scans (STIR and T2 gradient echo) of the knee
      to evaluate the PF joint cartilage. MRI scans were reviewed by an independent
      bone radiologist, whereas arthroscopic images were evaluated by an independent
      sports medicine fellowship-trained orthopaedic surgeon. RESULTS: Thirty-six
      patients (37 fractures) were available for follow-up at a minimum of 1 year
      (range: 12-49 months) after the index procedure. All but 2 fractures healed after
      the index procedure (94.6%). There was 1 radiographic malunion (2.7%). The mean
      Lysholm knee score was 82.14. Mean SF-36 physical and mental scores were 40.8 and
      46.0, respectively. Mean arc of knee motion was 124.4 degrees for the affected
      extremity compared with 127.2 degrees for the contralateral knee. One patient
      (2.7%) complained of mild pain at the scar, but no patient complained of anterior
      knee pain either at the PF joint or at the anterior proximal tibia. In 13 of 15
      patients undergoing an arthroscopic assessment of the PF joint, prenail and
      postnail insertion, no cartilage changes, or pressure points were seen either at
      the patella or at the trochlea groove. Two patients had grade II chondromalacia
      of the trochlea immediately after the procedure, but these did not correspond
      with either MRI scans or clinical findings at 1 year. When the remainder of the 1
      year MRI scans were reviewed, 1 knee (2.7%) in a patient that did not have an
      arthroscopic examination was found to have grade II chondromalacia in the PF
      joint, but this did not correlate with the clinical examination, which was
      normal. CONCLUSIONS: This is the first paper to critically document clinical and
      radiographic results using the percutaneous SP portal with the semiextended
      approach for IMN of the tibia. Our 1 year results indicate that the procedure
      resulted in excellent tibial alignment, union, and knee range of motion, with
      rare sequelae in the PF joint based on immediate arthroscopy and 1-year MRI scans
      and clinical examinations. Even more interesting was the absence of anterior
      tibial pain often found when a tibial nail is inserted in a standard fashion.

PMID- 25046414
TI  - The intramedullary nailing of fractures.

PMID- 25046416
TI  - In brief: generic celecoxib.

PMID- 25046415
TI  - The functional polymorphisms of VDR, GC and CYP2R1 are involved in the
      pathogenesis of autoimmune thyroid diseases.
AB  - Vitamin D is a multi-functional immune regulator, and a low serum concentration
      of vitamin D promotes autoimmune inflammation. In this study, we evaluate the
      association between the prognosis of autoimmune thyroid disease (AITD) and the
      functional polymorphisms of genes that regulate vitamin D metabolism. For 139
      Graves' disease (GD) patients, 116 Hashimoto's disease (HD) patients and 76
      control subjects, we genotyped the following polymorphisms using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP): vitamin D receptor
      (VDR): rs731236, rs7975232, rs2228570 and rs1544410; group-specific component
      (GC): rs7041 and rs4588; and CYP2R1: rs10741657. The frequency of the TT genotype
      for the rs731236 polymorphism was higher in GD patients than in HD patients (P =
      0.0147). The frequency of the C allele for the rs7975232 polymorphism was higher
      in GD patients than in control subjects (P = 0.0349). The proportion of GD
      patients whose anti-thyrotrophin receptor antibody (TRAb) level was >51% was
      higher in those with the CC genotype than in those with the CA+AA genotypes (P =
      0.0065). The frequency of the CC genotype for the rs2228570 polymorphism was
      higher in HD patients than in control subjects (P = 0.0174) and GD patients (P =
      0.0149). The frequency of the Gc1Gc1 genotype for the GC polymorphism and the AG
      genotype for the CYP2R1 polymorphism were lower in intractable GD than in GD in
      remission (P = 0.0093 and 0.0268, respectively). In conclusion, genetic
      differences in the VDR gene may be involved in the development of AITD and the
      activity of GD, whereas the genetic differences in the GC and CYP2R1 genes may be
      involved with the intractability of GD.

PMID- 25046417
TI  - Extended-release oxycodone and acetaminophen (Xartemis XR).

PMID- 25046418
TI  - Oral propranolol (Hemangeol) for infantile hemangioma.

PMID- 25046419
TI  - Ceritinib (Zykadia) for non-small cell lung cancer.

PMID- 25046420
TI  - A responsive neurostimulator device (RNS System) for epilepsy.

PMID- 25046421
TI  - In brief: Esomeprazole strontium.

PMID- 25046422
TI  - In brief: low-dose indomethacin (Tivorbex) for pain.

PMID- 25046423
TI  - Investigation of alpha-dicarbonyl compounds in baby foods by high-performance
      liquid chromatography coupled with electrospray ionization mass spectrometry.
AB  - Baby foods are exposed to elevated temperatures during processing treatments such
      as sterilization or spray drying. These treatments decompose sugars leading to
      the formation of alpha-dicarbonyl compounds that are of importance since they
      have been associated with several metabolic disorders. In this study, an
      analytical method based on high-performance liquid chromatography coupled with
      electrospray ionization mass spectrometry (HPLC-ESI-MS) was used to determine
      alpha-dicarbonyl compounds in baby foods. The method entailed aqueous extraction
      of alpha-dicarbonyl compounds from the samples and derivatization with o
      phenylenediamine prior to chromatographic analysis. The results indicated that
      major degradation product was 3-deoxyglucosone in the samples including cereal
      based infant formula, canned fruit and vegetable puree. Its concentration ranged
      between 3.9 and 827.1 mg/kg in infant formula and between 26.7 and 92.3 mg/kg in
      fruit puree samples. The concentrations of glucosone, 1-deoxyglucosone, 5
      hydroxymethyl-2-furfural, furfural, glyoxal, methylglyoxal, and dimethylglyoxal
      levels were rather low. 

PMID- 25046424
TI  - Voltammetric pH sensing using carbon electrodes: glassy carbon behaves similarly
      to EPPG.
AB  - Developing and building on recent work based on a simple sensor for pH
      determination using unmodified edge plane pyrolytic graphite (EPPG) electrodes,
      we present a voltammetric method for pH determination using a bare unmodified
      glassy carbon (GC) electrode. By exploiting the pH sensitive nature of quinones
      present on carbon edge-plane like sites within the GC, we show how GC electrodes
      can be used to measure pH. The electro-reduction of surface quinone groups on the
      glassy carbon electrode was characterised using cyclic voltammetry (CV) and
      optimised with square-wave voltammetry (SWV) at 298 K and 310 K. At both
      temperatures, a linear correlation was observed, corresponding to a 2 electron, 2
      proton Nernstian response over the aqueous pH range 1.0 to 13.1. As such,
      unmodified glassy carbon electrodes are seen to be pH dependent, and the
      Nernstian response suggests its facile use for pH sensing. Given the widespread
      use of glassy carbon electrodes in electroanalysis, the approach offers a method
      for the near-simultaneous measurement and monitoring of pH during such analyses. 

PMID- 25046425
TI  - Kinetic and structural characterization of tunnel-perturbing mutants in
      Bradyrhizobium japonicum proline utilization A.
AB  - Proline utilization A from Bradyrhizobium japonicum (BjPutA) is a bifunctional
      flavoenzyme that catalyzes the oxidation of proline to glutamate using fused
      proline dehydrogenase (PRODH) and Delta(1)-pyrroline-5-carboxylate dehydrogenase
      (P5CDH) domains. Recent crystal structures and kinetic data suggest an
      intramolecular channel connects the two active sites, promoting substrate
      channeling of the intermediate Delta(1)-pyrroline-5-carboxylate/glutamate-gamma
      semialdehyde (P5C/GSA). In this work, the structure of the channel was explored
      by inserting large side chain residues at four positions along the channel in
      BjPutA. Kinetic analysis of the different mutants revealed replacement of D779
      with Tyr (D779Y) or Trp (D779W) significantly decreased the overall rate of the
      PRODH-P5CDH channeling reaction. X-ray crystal structures of D779Y and D779W
      revealed that the large side chains caused a constriction in the central section
      of the tunnel, thus likely impeding the travel of P5C/GSA in the channel. The
      D779Y and D779W mutants have PRODH activity similar to that of wild-type BjPutA
      but exhibit significantly lower P5CDH activity, suggesting that exogenous P5C/GSA
      enters the channel upstream of Asp779. Replacement of nearby Asp778 with Tyr
      (D778Y) did not impact BjPutA channeling activity. Consistent with the kinetic
      results, the X-ray crystal structure of D778Y shows that the main channel pathway
      is not impacted; however, an off-cavity pathway is closed off from the channel.
      These findings provide evidence that the off-cavity pathway is not essential for
      substrate channeling in BjPutA. 

PMID- 25046426
TI  - High-throughput analysis of molecular orientation on surfaces by NEXAFS imaging
      of curved sample arrays.
AB  - Near-edge X-ray absorption fine structure (NEXAFS) spectroscopy provides detailed
      information about the orientation and alignment of thin films. NEXAFS is a
      synchrotron-based technique-the availability of beam-time per user is typically
      limited to no more than a few weeks per year. The limited availability is
      currently a true barrier for using NEXAFS in combinatorial studies of molecular
      alignment. We have recently demonstrated how large area full field NEXAFS imaging
      allows users to pursue combinatorial studies of surface chemistry. Now we report
      an extension of this approach which allows the acquisition of orientation
      information from a single NEXAFS image. An array with 80 elements (samples),
      containing eight series of different surface modifications, was mounted on a
      curved substrate allowing the collection of NEXAFS spectra with a range of
      orientations with respect to the X-ray beam. Images collected from this array
      show how hyperspectral NEXAFS data collected from curved surfaces can be used for
      high-throughput molecular orientation analysis. 

PMID- 25046427
TI  - Cytotoxic agents in sarcoidosis: which one should we choose?
AB  - PURPOSE OF REVIEW: Sarcoidosis is a granulomatous disease which affects multiple
      organs. Its therapeutic management is very challenging due to the heterogeneity
      in disease manifestation and clinical course, as well as the potential side
      effects of the immunosuppressive therapy. An overview of presently available
      second-line and third-line systemic agents is provided. RECENT FINDINGS: Because
      curative treatment is currently not available for sarcoidosis, nonspecific
      immunosuppression with prednisone remains the first-choice therapy. However, as
      chronic use of corticosteroids is accompanied with severe adverse events, timely
      implementation of appropriate steroid-sparing cytotoxic agents is important.
      Commonly prescribed second-line agents in sarcoidosis are methotrexate,
      azathioprine, leflunomide and hydroxychloroquine. Nevertheless, the evidence
      supporting their use is limited. Third-line treatment options, including tumor
      necrosis factor-alpha inhibitors infliximab and adalimumab and the experimental
      therapeutic rituximab, are currently reserved for patients refractory to standard
      therapy. SUMMARY: A better insight into the advantages and disadvantages of
      second-line and third-line treatment is important. The long-term effects of
      immunosuppressive agents, the optimal starting and maintenance dosages, and the
      best interval and discontinuation regimens should be elucidated. Identified
      associations of polymorphisms with treatment response suggest a step towards
      personalized medicine. Future research should focus on the role for
      pharmacogenetic and phenotypic predictors of treatment response and toxicity.

PMID- 25046428
TI  - Pulmonary hypertension associated with chronic obstructive lung disease and
      idiopathic pulmonary fibrosis.
AB  - PURPOSE OF REVIEW: Severe pulmonary hypertension worsens the prognosis of
      patients with chronic obstructive pulmonary disease (COPD) or idiopathic
      pulmonary fibrosis (IPF). With the aim of better understanding the pathogenesis
      of this event and identifying the possible targets for therapeutic intervention,
      a great deal of clinical and translational research is now focused on this
      relevant field of medicine. RECENT FINDINGS: Some studies that were published
      last year have helped to better define the clinical and physiological profiles of
      patients with COPD or IPF and severe pulmonary hypertension. The importance of
      pulmonary rehabilitation was confirmed, particularly in patients with pulmonary
      hypertension associated with IPF. Information on the use of drugs approved for
      the treatment of pulmonary arterial hypertension is still very limited, because
      of some limitations and selection biases in the studies' design. New strategies
      (i.e. the use of fasudil or sepiapterin in pulmonary hypertension associated with
      IPF) have been evaluated in animal models. SUMMARY: Pulmonary hypertension in
      COPD or IPF may range from mild to severe. When pulmonary hypertension is more
      advanced, it can drive a poor outcome. Therefore, future studies should focus on
      this subset.

PMID- 25046429
TI  - Advanced pulmonary sarcoidosis.
AB  - PURPOSE OF REVIEW: To present an update on the most recent contributions in
      advanced pulmonary sarcoidosis (APS). RECENT FINDINGS: Pathology is better
      described and the differences between fibrosing pulmonary sarcoidosis and usual
      interstitial pneumonia (UIP) are clarified. Serial spirometry is the most
      reliable tool for monitoring evolution. Survival may be predicted by an
      integrative algorithm based on pulmonary function and computed tomography (CT).
      SUMMARY: APS is characterized by significant fibrocystic pulmonary lesions at CT
      and pathology. There are two main patterns of APS, one with predominant central
      bronchovascular distortion, often associated with airflow limitation, and the
      other with predominant honeycombing with a different location than in UIP with
      severe restrictive impairment and very low diffusion capacity of the lung for
      carbon monoxide. APS may be burnt out but is most often still active as evidenced
      by several findings, including on F-fluorodeoxyglucose-PET. There is an increased
      mortality and morbidity with chronic respiratory insufficiency, pulmonary
      hypertension stemming from multiple mechanisms, chronic pulmonary aspergillosis
      and extra infections. Acute worsening episodes are frequent. Serial spirometry,
      particularly forced vital capacity, is the most reliable tool for monitoring
      evolution. A new elegant algorithm based on pulmonary function and CT may predict
      survival. Despite important stakes, there is still a lack of therapeutic
      recommendations. However, the use of antisarcoidosis treatment is most often
      required at least as a temporary trial. Finally, the effect of pulmonary
      hypertension treatment has recently been the object of further evaluation.

PMID- 25046430
TI  - Production of tongue twisters by speakers with partial glossectomy.
AB  - Abstract A partial glossectomy can affect speech production. The goal of this
      study was to investigate the effect of the presence of a tumour as well as the
      glossectomy surgery on the patients' production of tongue twisters with the
      sounds [t] and [k]. Fifteen patients with tongue cancer and 10 healthy controls
      took part in the study. The outcome measures were the patients' speech
      acceptability, rate of errors, the time needed to produce the tongue twisters,
      pause duration between item repetitions and the tongue shape during the
      production of the consonants [t] and [k] before and after surgery. The patients'
      speech acceptability deteriorated after the surgery. Compared to controls, the
      patients' productions of the tongue twisters were slower but not more errorful.
      Following the surgery, their speed of production did not change, but the rate of
      errors was higher. Pause duration between items was longer in the patients than
      in the controls but did not increase from before to after surgery. Analysis of
      the patients' tongue shapes for the productions of [t] and [k] indicated a higher
      elevation following the surgery for the patients with flap reconstructions. The
      results demonstrated that the surgical resection of the tongue changed the error
      rate but not the speed of production for the patient. The differences in pause
      duration also indicate that the tumour and the surgical resection of the tongue
      may impact the phonological planning of the tongue twister. 

PMID- 25046431
TI  - Prevalence of ear disease in dogs undergoing multidetector thin-slice computed
      tomography of the head.
AB  - Previous reports describing the prevalence of ear diseases in dogs have primarily
      been based on dogs presenting with clinical signs of disease. The prevalence of
      subclinical ear disease remains unknown. The purpose of this cross-sectional
      retrospective study was to describe the prevalence of lesions consistent with
      middle and external ear disease in dogs presented for multidetector computed
      tomography (CT) of the head and/or cranial cervical spine at our hospital during
      the period of July 2011 and August 2013. For each included dog, data recorded
      were signalment, CT findings, diagnosis, and treatment. A total of 199 dogs met
      inclusion criteria. Nineteen dogs (9.5%) were referred for evaluation of
      suspected ear disease and 27 dogs (13.5%) had histories or physical examination
      findings consistent with otitis externa. A total of 163 dogs (81.9%) had CT
      lesions consistent with external ear disease (i.e. ear canal mineralization,
      external canal thickening, and/or narrowing of the external canal). Thirty-nine
      dogs (19.5%) had CT lesions consistent with middle ear disease (i.e. soft tissue
      attenuating/fluid material in the tympanic bullae, bulla wall thickening or
      lysis, and/or periosteal proliferation of the temporal bone). Findings from this
      study indicated that the prevalence of external and middle ear disease in dogs
      could be higher than that previously reported. 

PMID- 25046432
TI  - Affinity of molecular ions for DNA structures is determined by solvent-accessible
      surface area.
AB  - It is considered that Hoogsteen base pairs and DNA triplex structures play
      important roles in cellular processes even though these structures are less than
      duplexes of Watson-Crick base pairs. Molecular ions clearly affect the stability
      of DNA structures in vivo; however, the mechanisms are unknown. Here, we
      investigated the effects of sodium ions, choline ions, and tetramethylammonium
      ions on DNA triplexes using molecular dynamics simulations. We found that
      nonpolar interactions, which are associated with van der Waals interactions, and
      solvent-accessible surface area were more important than polar or electrostatic
      interactions in determining the affinity of a molecular cation for the DNA groove
      areas. The free energy gain due to a cation that fit optimally within a DNA
      groove was larger than the free energy loss due to the effect of dehydration.
      Cations with shapes complementary to that of a particular DNA groove
      configuration stabilized triplex formation, but cations that disturbed hydrogen
      bonds between DNA bases were destabilizing. These stabilizing and destabilizing
      mechanisms of molecular cations were also applicable to a DNA duplex composed of
      Watson-Crick base pairs. The molecular-level view of cation interactions with DNA
      structures will guide the design of DNA devices, DNA-based drugs, and genetic
      therapies. 

PMID- 25046433
TI  - Position of transmembrane helix 6 determines receptor G protein coupling
      specificity.
AB  - G protein coupled receptors (GPCRs) transmit extracellular signals into the cell
      by binding and activating different intracellular signaling proteins, such as G
      proteins (Galphabetagamma, families Gi, Gs, Gq, G12/13) or arrestins. To address
      the issue of Gs vs Gi coupling specificity, we carried out molecular dynamics
      simulations of lipid-embedded active beta2-adrenoceptor (beta2AR*) in complex
      with C-terminal peptides derived from the key interaction site of Galpha
      (GalphaCT) as surrogate of Galphabetagamma. We find that GialphaCT and GsalphaCT
      exploit distinct cytoplasmic receptor conformations that coexist in the
      uncomplexed beta2AR*. The slim GialphaCT stabilizes a beta2AR* conformation, not
      accessible to the bulkier GsalphaCT, which requires a larger TM6 outward tilt for
      binding. Our results suggest that the TM6 conformational heterogeneity regulates
      the catalytic activity of beta2AR* toward Gi or Gs. 

PMID- 25046434
TI  - Analysis of oxidative stress in zebrafish embryos.
AB  - High levels of reactive oxygen species (ROS) may cause a change of cellular redox
      state towards oxidative stress condition. This situation causes oxidation of
      molecules (lipid, DNA, protein) and leads to cell death. Oxidative stress also
      impacts the progression of several pathological conditions such as diabetes,
      retinopathies, neurodegeneration, and cancer. Thus, it is important to define
      tools to investigate oxidative stress conditions not only at the level of single
      cells but also in the context of whole organisms. Here, we consider the zebrafish
      embryo as a useful in vivo system to perform such studies and present a protocol
      to measure in vivo oxidative stress. Taking advantage of fluorescent ROS probes
      and zebrafish transgenic fluorescent lines, we develop two different methods to
      measure oxidative stress in vivo: i) a "whole embryo ROS-detection method" for
      qualitative measurement of oxidative stress and ii) a "single-cell ROS detection
      method" for quantitative measurements of oxidative stress. Herein, we demonstrate
      the efficacy of these procedures by increasing oxidative stress in tissues by
      oxidant agents and physiological or genetic methods. This protocol is amenable
      for forward genetic screens and it will help address cause-effect relationships
      of ROS in animal models of oxidative stress-related pathologies such as
      neurological disorders and cancer. 

PMID- 25046435
TI  - Contribution of cationic amino acids toward the inhibition of Arg-specific
      cysteine proteinase (Arg-gingipain) by the antimicrobial dodecapeptide, CL(14
      25), from rice protein.
AB  - CL(14-25), a dodecapeptide, exhibits antimicrobial activity against Porphyromonas
      gingivalis with the 50% growth-inhibitory concentration (IC50 ) value of 145 uM,
      and arginine-specific gingipain (Rgp)-inhibitory activity. Kinetic analysis
      revealed that CL(14-25) is a mixed-type inhibitor, with inhibition constants (Ki
      and Ki ' values) of 1.4 * 10(-6) M and 4.3 * 10(-6) M, respectively. To elucidate
      the contributions of four cationic amino acid residues at the N- and C-termini of
      CL(14-25) toward Rgp-inhibitory activity, we investigated the Rgp-inhibitory
      activities of truncated and alanine-substituted analogs of CL(14-25). Rgp
      inhibitory activities significantly decreased by truncated analogs, CL(15-25) and
      CL(16-25), whereas those of CL(14-24) and CL(14-23) were almost as high as that
      of CL(14-25). Rgp-inhibitory activities of alanine-substituted analogs, CL(R14A)
      and CL(R14A, R15A) also significantly decreased, whereas those of CL(K25A) and
      CL(R24A, K25A) were higher than that of CL(14-25). These results suggest that the
      arginine residue at position 15 substantially contributes to the Rgp-inhibitory
      activity and that the arginine residue at position 14 plays important roles in
      exerting Rgp-inhibitory activity. In this study, we demonstrated that CL(K25A)
      was a potent, dual function, peptide inhibitor candidate, exhibiting Rgp
      inhibitory activity with Ki and Ki ' of 9.6 * 10(-7) M and 1.9 * 10(-6) M,
      respectively, and antimicrobial activity against P. gingivalis with an IC50 value
      of 51 uM.

PMID- 25046436
TI  - MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal
      dialysis.
AB  - TGF-beta/Smad3 signaling plays a pivotal role in the pathogenesis of peritoneal
      fibrosis associated with peritoneal dialysis (PD). MicroRNA-29 (miR-29) is known
      as a potent downstream inhibitor of TGF-beta/Smad3 in renal fibrosis. In this
      study, we examined the therapeutic potential for miR-29b on PD-related peritoneal
      fibrosis in a mouse model of PD induced by daily infusion of 4.25% dextrose
      containing PD fluid (PDF). MiR-29b-expressing plasmid was delivered into the
      peritoneum via an ultrasound-microbubble-mediated system before and at day 14
      after PDF. We found that mice on PD developed peritoneal fibrosis with impaired
      peritoneal function, which was associated with a loss of miR-29b. In contrast,
      overexpression of miR-29b before the PDF infusion showed a protective effect on
      peritoneal fibrosis including EMT and prevented peritoneal dysfunction. Moreover,
      delayed miR-29b treatment until peritoneal fibrosis was established at day 14
      also halted the progression of peritoneal fibrosis at day 28. Further studies
      identified that blockade of the Sp1-TGF-beta/Smad3 pathway may be a mechanism by
      which miR-29b inhibited peritoneal fibrosis. In conclusion, treatment with miR
      29b may represent a novel and effective therapy for PD-associated peritoneal
      fibrosis. 

PMID- 25046437
TI  - Characterization of cultured cholangiocytes isolated from livers of patients with
      primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic, idiopathic cholangiopathy. The
      role of cholangiocytes (biliary epithelial cells) in PSC pathogenesis is unknown
      and remains an active area of research. Here, through cellular, molecular and
      next-generation sequencing (NGS) methods, we characterize and identify phenotypic
      and signaling features of isolated PSC patient-derived cholangiocytes. We
      isolated cholangiocytes from stage 4 PSC patient liver explants by dissection,
      differential filtration and immune-magnetic bead separation. We maintained
      cholangiocytes in culture and assessed for: (i) cholangiocyte, cell adhesion and
      inflammatory markers; (ii) proliferation rate; (iii) transepithelial electrical
      resistance (TEER); (iv) cellular senescence; and (v) transcriptomic profiles by
      NGS. We used two well-established normal human cholangiocyte cell lines (H69 and
      NHC) as controls. Isolated PSC cells expressed cholangiocyte (eg, cytokeratin 7
      and 19) and epithelial cell adhesion markers (EPCAM, ICAM) and were negative for
      hepatocyte and myofibroblast markers (albumin, alpha-actin). Proliferation rate
      was lower for PSC compared with normal cholangiocytes (4 vs 2 days, respectively,
      P<0.01). Maximum TEER was also lower in PSC compared with normal cholangiocytes
      (100 vs 145 Omegacm(2), P<0.05). Interleukin-6 (IL-6) and IL-8 (protein and mRNA)
      were both increased compared with NHCs and H69s (all P<0.01). The proportion of
      cholangiocytes staining positive for senescence-associated beta-galactosidase was
      higher in PSC cholangiocytes compared with NHCs (48% vs 5%, P<0.01). Finally, NGS
      confirmed cholangiocyte marker expression in isolated PSC cholangiocytes and
      extended our findings regarding pro-inflammatory and senescence-associated
      signaling. In conclusion, we have demonstrated that high-purity cholangiocytes
      can be isolated from human PSC liver and grown in primary culture. Isolated PSC
      cholangiocytes exhibit a phenotype that may reflect their in vivo contribution to
      disease and serve as a vital tool for in vitro investigation of biliary
      pathobiology and identification of new therapeutic targets in PSC.

PMID- 25046438
TI  - Differential effects of Akt1 signaling on short- versus long-term consequences of
      myocardial infarction and reperfusion injury.
AB  - A specific role for Akt1 in events following myocardial infarction (MI) and
      ischemia/reperfusion (I/R) injury is not known. We aimed to determine whether
      Akt1 deletion in in vivo mouse models of MI and after ischemia I/R injury would
      alter myocyte survival, cardiac function, and fibrosis. Akt1(+/+) and Akt1(-/-)
      mice were subjected to MI and I/R, followed by assessment of downstream signaling
      events and functional consequences. Although no difference in infarct size
      following short-term MI was observed between Akt1(+/+) and Akt1(-/-) mice, I/R
      caused substantially more cardiomyocyte apoptosis and tissue damage in Akt1(-/-)
      mice compared with Akt1(+/+). Importantly, these effects were reversed upon
      pretreatment with GSK-3 inhibitor SB415286. Counterintuitively, Akt1(-/-) hearts
      exhibited improved cardiac function following long-term MI compared with
      Akt1(+/+) and were associated with reduced fibrosis in the left ventricle (LV).
      Our results demonstrate that Akt1-mediated inhibition of GSK-3 activity is
      critical for cardioprotection following I/R. However, in the long term, Akt1
      contributes to fibrosis in post-MI hearts and might exacerbate cardiac
      dysfunction showing dichotomous role for Akt1 in cardiac remodeling after MI. Our
      data suggest that better understanding of the Akt1/GSK-3 pathway may provide
      insights for better therapeutic strategies in post-MI tissues. 

PMID- 25046439
TI  - Rac1 regulates platelet shedding of CD40L in abdominal sepsis.
AB  - Matrix metalloproteinase-9 (MMP-9) regulates platelet shedding of CD40L in
      abdominal sepsis. However, the signaling mechanisms controlling sepsis-induced
      shedding of CD40L from activated platelets remain elusive. Rac1 has been reported
      to regulate diverse functions in platelets; we hypothesized herein that Rac1
      might regulate platelet shedding of CD40L in sepsis. The specific Rac1 inhibitor
      NSC23766 (N6-[2-[[4-(diethylamino)-1-methylbutyl] amino]-6-methyl-4-pyrimidinyl]
      2 methyl-4, 6-quinolinediamine trihydrochloride) was administered to mice
      undergoing cecal ligation and puncture (CLP). Levels of CD40L and MMP-9 in
      plasma, platelets, and neutrophils were determined by use of ELISA, western blot,
      and confocal microscopy. Platelet depletion abolished the CLP-induced increase in
      plasma levels of CD40L. Rac1 activity was significantly increased in platelets
      from septic animals. Administration of NSC23766 abolished the CLP-induced
      enhancement of soluble CD40L levels in the plasma. Moreover, Rac1 inhibition
      completely inhibited proteinase-activated receptor-4-induced surface mobilization
      and secretion of CD40L in isolated platelets. CLP significantly increased plasma
      levels of MMP-9 and Rac1 activity in neutrophils. Treatment with NSC23766
      markedly attenuated MMP-9 levels in the plasma from septic mice. In addition,
      Rac1 inhibition abolished chemokine-induced secretion of MMP-9 from isolated
      neutrophils. Finally, platelet shedding of CD40L was significantly reduced in
      response to stimulation with supernatants from activated MMP-9-deficient
      neutrophils compared with supernatants from wild-type neutrophils, indicating a
      direct role of neutrophil-derived MMP-9 in regulating platelet shedding of CD40L.
      Our novel data suggest that sepsis-induced platelet shedding of CD40L is
      dependent on Rac1 signaling. Rac1 controls surface mobilization of CD40L on
      activated platelets and MMP-9 secretion from neutrophils. Thus, our findings
      indicate that targeting Rac1 signaling might be a useful way to control
      pathologic elevations of CD40L in the systemic circulation in abdominal sepsis. 

PMID- 25046441
TI  - Production and isolation of axons from sensory neurons for biochemical analysis
      using porous filters.
AB  - Neuronal axons use specific mechanisms to mediate extension, maintain integrity,
      and induce degeneration. An appropriate balance of these events is required to
      shape functional neuronal circuits. The protocol described here explains how to
      use cell culture inserts bearing a porous membrane (filter) to obtain large
      amounts of pure axonal preparations suitable for examination by conventional
      biochemical or immunocytochemical techniques. The functionality of these filter
      inserts will be demonstrated with models of developmental pruning and Wallerian
      degeneration, using explants of embryonic dorsal root ganglion. Axonal integrity
      and function is compromised in a wide variety of neurodegenerative pathologies.
      Indeed, it is now clear that axonal dysfunction appears much earlier in the
      course of the disease than neuronal soma loss in several neurodegenerative
      diseases, indicating that axonal-specific processes are primarily targeted in
      these disorders. By obtaining pure axonal samples for analysis by molecular and
      biochemical techniques, this technique has the potential to shed new light into
      mechanisms regulating the physiology and pathophysiology of axons. This in turn
      will have an impact in our understanding of the processes that drive degenerative
      diseases of the nervous system. 

PMID- 25046440
TI  - Increased expression of (pro)renin receptor does not cause hypertension or
      cardiac and renal fibrosis in mice.
AB  - Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their
      enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro.
      Expression of PRR is increased in the heart and kidney of hypertensive and
      diabetic animals, but its causative role in organ damage is still unclear. To
      determine whether increased expression of PRR is sufficient to induce cardiac or
      renal injury, we generated a mouse that constitutively overexpresses PRR by
      knocking-in the Atp6ap2/PRR gene in the hprt locus under the control of a CMV
      immediate early enhancer/chicken beta-actin promoter. Mice were backcrossed in
      the C57Bl/6 and FVB/N strain and studied at the age of 12 months. In spite of a
      25- to 80-fold renal and up to 400-fold cardiac increase in Atp6ap2/PRR
      expression, we found no differences in systolic blood pressure or albuminuria
      between wild-type and PRR overexpressing littermates. Histological examination
      did not show any renal or cardiac fibrosis in mutant mice. This was supported by
      real-time PCR analysis of inflammatory markers as well as of pro-fibrotic genes
      in the kidney and collagen in cardiac tissue. To determine whether the
      concomitant increase of renin would trigger fibrosis, we treated PRR
      overexpressing mice with the angiotensin receptor-1 blocker losartan over a
      period of 6 weeks. Renin expression increased eightfold in the kidney but no
      renal injury could be detected. In conclusion, our results suggest no major role
      for PRR in organ damage per se or related to its function as a receptor of renin.

PMID- 25046442
TI  - Impact of long-term N, P, K, and NPK fertilization on the composition and
      potential functions of the bacterial community in grassland soil.
AB  - Soil abiotic and biotic interactions govern important ecosystem processes.
      However, the mechanisms behind these interactions are complex, and the links
      between specific environmental factors, microbial community structures, and
      functions are not well understood. Here, we applied DNA shotgun metagenomic
      techniques to investigate the effect of inorganic fertilizers N, P, K, and NPK on
      the bacterial community composition and potential functions in grassland soils in
      a 54-year experiment. Differences in total and available nutrients were found in
      the treatment soils; interestingly, Al, As, Mg, and Mn contents were variable in
      N, P, K, and NPK treatments. Bacterial community compositions shifted and
      Actinobacteria were overrepresented under the four fertilization treatments
      compared to the control. Redundancy analysis of the soil parameters and the
      bacterial community profiles showed that Mg, total N, Cd, and Al were linked to
      community variation. Using correlation analysis, Acidobacteria, Bacteroidetes,
      and Verrucomicrobia were linked similarly to soil parameters, and Actinobacteria
      and Proteobacteria were linked separately to different suites of parameters.
      Surprisingly, we found no fertilizers effect on microbial functional profiles
      which supports functional redundancy as a mechanism for stabilization of
      functions during changes in microbial composition. We suggest that functional
      profiles are more resistant to environmental changes than community compositions
      in the grassland ecosystem. 

PMID- 25046443
TI  - Ichthyosis in the Neonatal Setting.
AB  - BACKGROUND: There exists a group of rare, inherited scaly skin disorders,
      generally termed ichthyosis, that can be evident in the infant at the time of
      birth. Phenotypes for this disorder span the gamut of severity and may pose
      complex challenges to the healthcare provider. PURPOSE: This article explores the
      3 most common nonsyndromic forms of ichthyosis seen in neonates as follows: X
      linked recessive, lamellar, and bullous congenital ichthyosiform erythroderma.
      Moreover, harlequin ichthyosis, a lamellar subtype, is highlighted for being the
      most severe, clinically problematic, and often lethal form of the disorder.
      FINDINGS/RESULTS: A description of each of these types and their incidence is
      included, followed by an explanation of the genetic mutations causing them. The
      phenotypes and natural history are reviewed, as is expected management of the
      disorder throughout the patient's lifetime. IMPLICATIONS FOR PRACTICE:
      Considerations for the neonatal nurse practitioner charged with caring for these
      patients, including specific recommendations for care in the clinical setting,
      are discussed. Additionally, genetic counseling and the risks of reoccurrence are
      explored. IMPLICATIONS FOR RESEARCH: Given the rare nature of this disorder,
      further research is warranted so that healthcare providers are prepared to
      provide optimal care to these fragile patients.

PMID- 25046444
TI  - Considerations in meeting protein needs of the human milk-fed preterm infant.
AB  - Preterm infants provided with sufficient nutrition to achieve intrauterine growth
      rates have the greatest potential for optimal neurodevelopment. Although human
      milk is the preferred feeding for preterm infants, unfortified human milk
      provides insufficient nutrition for the very low-birth-weight infant. Even after
      fortification with human milk fortifier, human milk often fails to meet the high
      protein needs of the smallest preterm infants, and additional protein
      supplementation must be provided. Although substantial evidence exists to support
      quantitative protein goals for human milk-fed preterm infants, the optimal type
      of protein for use in human milk fortification remains uncertain. This question
      was addressed through a PubMed literature search of prospective clinical trials
      conducted since 1990 in preterm or low-birth-weight infant populations. The
      following 3 different aspects of protein quality were evaluated: whey-to-casein
      ratio, hydrolyzed versus intact protein, and bovine milk protein versus human
      milk protein. Because of a scarcity of current studies conducted with fortified
      human milk, studies examining protein quality using preterm infant formulas were
      included to address certain components of the clinical question. Twenty-six
      studies were included in the review study. No definite advantage was found for
      any specific whey-to-casein ratio. Protein hydrolyzate products with appropriate
      formulations can support adequate growth and biochemical indicators of nutrition
      status and may reduce gastrointestinal transit time, gastroesophageal reflux
      events, and later incidence of atopic dermatitis in some infants. Plasma amino
      acid levels similar to those of infants fed exclusive human milk-based diets can
      be achieved with products composed of a mixture of bovine proteins, peptides, and
      amino acids formulated to replicate the amino acid composition of human milk.
      Growth and biochemical indicators of nutrition status are similar for infants fed
      human milk fortified with human milk protein and bovine milk protein. 

PMID- 25046445
TI  - The bovine lung in biomedical research: visually guided bronchoscopy,
      intrabronchial inoculation and in vivo sampling techniques.
AB  - There is an ongoing search for alternative animal models in research of
      respiratory medicine. Depending on the goal of the research, large animals as
      models of pulmonary disease often resemble the situation of the human lung much
      better than mice do. Working with large animals also offers the opportunity to
      sample the same animal repeatedly over a certain course of time, which allows
      long-term studies without sacrificing the animals. The aim was to establish in
      vivo sampling methods for the use in a bovine model of a respiratory Chlamydia
      psittaci infection. Sampling should be performed at various time points in each
      animal during the study, and the samples should be suitable to study the host
      response, as well as the pathogen under experimental conditions. Bronchoscopy is
      a valuable diagnostic tool in human and veterinary medicine. It is a safe and
      minimally invasive procedure. This article describes the intrabronchial
      inoculation of calves as well as sampling methods for the lower respiratory
      tract. Videoendoscopic, intrabronchial inoculation leads to very consistent
      clinical and pathological findings in all inoculated animals and is, therefore,
      well-suited for use in models of infectious lung disease. The sampling methods
      described are bronchoalveolar lavage, bronchial brushing and transbronchial lung
      biopsy. All of these are valuable diagnostic tools in human medicine and could be
      adapted for experimental purposes to calves aged 6-8 weeks. The samples obtained
      were suitable for both pathogen detection and characterization of the severity of
      lung inflammation in the host. 

PMID- 25046447
TI  - Bayesian evaluation of inequality constrained hypotheses.
AB  - Bayesian evaluation of inequality constrained hypotheses enables researchers to
      investigate their expectations with respect to the structure among model
      parameters. This article proposes an approximate Bayes procedure that can be used
      for the selection of the best of a set of inequality constrained hypotheses based
      on the Bayes factor in a very general class of statistical models. The software
      package BIG is provided such that psychologists can use the approach proposed for
      the analysis of their own data. To illustrate the approximate Bayes procedure and
      the use of BIG, we evaluate inequality constrained hypotheses in a path model and
      a logistic regression model. Two simulation studies on the performance of our
      approximate Bayes procedure show that it results in accurate Bayes factors.

PMID- 25046448
TI  - Evaluating order-constrained hypotheses for circular data from a between-within
      subjects design.
AB  - Researchers in psychology often encounter data measured in angles (e.g.,
      directions, or measurements on circular scales such as the circumplex model of
      affect). Due to periodicity, the evaluation of these circular data requires
      special statistical methods. This article introduces new tests for the analysis
      of order-constrained hypotheses for circular data. Through these tests,
      researchers can evaluate their expectations regarding the outcome of an
      experiment directly by representing their ideas in the form of a hypothesis
      containing inequality constraints. The resulting data analysis is generally more
      powerful than one using null hypothesis testing. An example of circular data from
      psychology is presented to illustrate the use of the tests. Results from a
      simulation study show that the tests perform well in terms of type I error and
      power.

PMID- 25046446
TI  - Pulsed electron paramagnetic resonance study of domain docking in neuronal nitric
      oxide synthase: the calmodulin and output state perspective.
AB  - The binding of calmodulin (CaM) to neuronal nitric oxide synthase (nNOS) enables
      formation of the output state of nNOS for nitric oxide production. Essential to
      NOS function is the geometry and dynamics of CaM docking to the NOS oxygenase
      domain, but little is known about these details. In the present work, the domain
      docking in a CaM-bound oxygenase/FMN (oxyFMN) construct of nNOS was investigated
      using the relaxation-induced dipolar modulation enhancement (RIDME) technique,
      which is a pulsed electron paramagnetic resonance technique sensitive to the
      magnetic dipole interaction between the electron spins. A cysteine was introduced
      at position 110 of CaM, after which a nitroxide spin label was attached at the
      position. The RIDME study of the magnetic dipole interaction between the spin
      label and the ferric heme centers in the oxygenase domain of nNOS revealed that,
      with increasing [Ca(2+)], the concentration of nNOS.CaM complexes increases and
      reaches a maximum at [Ca(2+)]/[CaM] >= 4. The RIDME kinetics of CaM-bound nNOS
      represented monotonous decays without well-defined oscillations. The analysis of
      these kinetics based on the structural models for the open and docked states has
      shown that only about 15 +/- 3% of the CaM-bound nNOS is in the docked state at
      any given time, while the remaining 85 +/- 3% of the protein is in the open
      conformations characterized by a wide distribution of distances between the bound
      CaM and the oxygenase domain. The results of this investigation are consistent
      with a model that the Ca(2+)-CaM interaction causes CaM docking with the
      oxygenase domain. The low population of the docked state indicates that the CaM
      controlled docking between the FMN and heme domains is highly dynamic. 

PMID- 25046449
TI  - Accuracy in parameter estimation in cluster randomized designs.
AB  - When planning to conduct a study, not only is it important to select a sample
      size that will ensure adequate statistical power, often it is important to select
      a sample size that results in accurate effect size estimates. In cluster
      randomized designs (CRD), such planning presents special challenges. In CRD
      studies, instead of assigning individual objects to treatment conditions, objects
      are grouped in clusters, and these clusters are then assigned to different
      treatment conditions. Sample size in CRD studies is a function of 2 components:
      the number of clusters and the cluster size. Planning to conduct a CRD study is
      difficult because 2 distinct sample size combinations might be associated with
      similar costs but can result in dramatically different levels of statistical
      power and accuracy in effect size estimation. Thus, we present a method that
      assists researchers in finding the least expensive sample size combination that
      still results in adequate accuracy in effect size estimation. Alternatively, if
      researchers have a fixed budget, they can select the sample size combination that
      results in the most precise estimate of effect size. A free computer program that
      automates these procedures is available.

PMID- 25046450
TI  - Ambivalence About Interpersonal Problems and Traits Predicts Cross-Situational
      Variability of Social Behavior.
AB  - Multiple theoretical perspectives suggest that maladjusted personality is
      characterized by not only distress, but also opposing or "ambivalent" self
      perceptions and behavioral lability across social interactions. However, the
      degree to which ambivalence about oneself predicts cross-situational variability
      in social behavior has not been examined empirically. Using the interpersonal
      circumplex (IPC) as a nomological framework, the present study investigated the
      extent to which endorsing opposing or "ambivalent" tendencies on IPC measures
      predicted variability in social behavior across a range of hypothetical
      interpersonal scenarios (Part 1; N = 288) and naturalistic social interactions
      (Part 2; N = 192). Ambivalent responding for interpersonal problems and traits
      was associated with measures of distress, maladaptive interpersonal tendencies,
      and greater variability of social behavior across both hypothetical and daily
      social interactions, though more consistently for interpersonal problems. More
      conservative tests suggested that ambivalence predicted some indexes of
      behavioral variability even when accounting for mean levels and squared means of
      social behaviors, vector length, gender, and depressive symptoms. Results suggest
      that processes theorized as typifying personality disorder may apply more broadly
      to personality maladjustment occurring outside of clinical samples.

PMID- 25046451
TI  - Cytotoxic chemotherapy in the contemporary management of metastatic castration
      resistant prostate cancer (mCRPC).
AB  - For several years, docetaxel was the only treatment shown to improve survival of
      patients with metastatic castration-resistant prostate cancer (mCRPC). There are
      now several novel agents available, although chemotherapy with docetaxel and
      cabazitaxel continues to play an important role. However, the increasing number
      of available agents will inevitably affect the timing of chemotherapy and
      therefore it may be important to offer this approach before declining performance
      status renders patients ineligible for chemotherapy. Patient selection is also
      important to optimise treatment benefit. The role of predictive biomarkers has
      assumed greater importance due to the development of multiple agents and
      resistance to available agents. In addition, the optimal sequence of treatments
      remains undefined and requires further study in order to maximize long-term
      outcomes. We provide an overview of the clinical data supporting the role of
      chemotherapy in the treatment of mCRPC and the emerging role in metastatic
      castration-sensitive prostate cancer. We review the key issues in the management
      of patients including selection of patients for chemotherapy, when to start
      chemotherapy, and how best to sequence treatments to maximise outcomes. In
      addition, we briefly summarise the promising new chemotherapeutic agents in
      development in the context of emerging therapies. 

PMID- 25046452
TI  - Xp21/A translocation: a rarely considered genetic cause for manifesting carriers
      of duchenne muscular dystrophy.
AB  - Clinically manifesting carriers of Duchenne muscular dystrophy (DMD) are rare
      among the pediatric population. A standardized diagnostic procedure in supposed
      DMD carriers entails performing a Multiplex Ligation-dependent Probe
      Amplification analysis of the DMD gene first, then taking a muscle biopsy to
      confirm reduced dystrophin levels and/or finally a complete sequencing of the DMD
      gene. We describe a girl with high-elevated creatine kinase, myalgia, and
      cardiomyopathy. Muscle biopsy showed a dystrophic pattern and nearly absent
      expression of dystrophin. Diagnosis could not be confirmed by molecular genetic
      procedures. Because of a mild mental retardation, a chromosome analysis and
      molecular karyotyping were performed, revealing a balanced translocation
      t(X;4)(p21;q31).arr(1-22,X)x2 dn with breakpoint on the X-chromosome within an
      intron of the DMD gene. The inactivation of the nonderivative X-chromosome was
      found to be in a nonrandom pattern, resulting in a functionally balanced
      karyotype and thus leading to a manifesting DMD carrier in this case. Chromosome
      analysis should be recommended in cases of genetically unsolved DMD carriers as a
      part of the standard genetic procedures. 

PMID- 25046453
TI  - Tailoring pigment dispersants with polyisobutylene twin-tail structures for
      electrowetting display application.
AB  - We have designed a class of highly hydrophobic dispersants for finely dispersing
      carbon black and organic pigment nanoparticles in apolar mediums. The synthesis
      involved the use of polyisobutylene-g-succinic anhydride (PIB-SA) and judiciously
      selected amines by amidation and imidation. The structures were characterized by
      infrared spectroscopy for anhydride functionalities in the starting materials and
      amide/imide linkages in the products. These polymeric forms of dispersants were
      structurally varied with respects to their PIB molecular weight, twin-tails, and
      linkages. Their relative performance for dispersing six different pigments in
      decane was evaluated against solution homogeneity, viscosity, stability, and
      particle size. The fine dispersion was achieved at particle sizes of ca. 100 nm,
      with the viscosity as low as 2-3 cP. The measurement of zeta potentials, which
      varied from -39.8 to -5.1 mV with pigment addition, revealed a strong surface
      charge interaction between pigment and PIB dispersant molecules. Examination by
      TEM (transmission electronic microscope) showed the homogeneous dispersion of the
      primary structures of pigment particles at ca. 20 nm in diameter. The polymeric
      dispersants with different PIB tails and imide functionalities could be tailored
      for pigment stability in the oil phase, which is potentially suitable for the
      electrowetting devices. 

PMID- 25046454
TI  - Non-random geographic distribution of patients with cutaneous T-cell lymphoma in
      the Greater Pittsburgh Area.
AB  - BACKGROUND: Environmental hazards may play a role in the etiology of cutaneous T
      cell lymphoma (CTCL). Some studies have found an increased incidence of CTCL
      among workers in chemical science, transportation, and manufacturing industries,
      but other studies have not. This discrepancy may be attributable to population
      migration, complicating accurate assessment of lifetime exposures. The Pittsburgh
      population has very low migration rates and most CTCL patients seen at the
      University of Pittsburgh Medical Center (UPMC) Cutaneous Lymphoma Center are life
      long local residents. The Greater Pittsburgh Area used to be an industrial hub.
      There are residential communities positioned within close proximity to inactive
      industrial sites that continue to contain pollutants. OBJECTIVE: To determine
      whether CTCL patients' residences cluster within specific Pittsburgh regions, in
      particular, those with high levels of environmental pollutants. METHODS: Our
      study included patients diagnosed with CTCL at the UPMC Cutaneous Lymphoma Center
      between 2000 and 2012. We mapped the longitudinal and latitudinal coordinates of
      patients' residences at diagnosis, superfund sites, toxic release inventory
      sites, particular matter levels, and dermatologists' offices using ArcMap 10.1.
      We then performed a SaTScan analysis using zip codes to assess for geographic
      clustering of patients' residences in the Pittsburgh metropolitan statistical
      area. We assessed for a correlation between case distribution and both
      environmental hazards sites and dermatologist density in the area. RESULTS: We
      identified 274 patients with CTCL in the Greater Pittsburgh area. We identified a
      statistically significant geographic cluster (p<.001) in zip code 15213, which is
      the most densely populated neighborhood in Pittsburgh and the site of the
      region's only CTCL clinic. We observed no relationship between the locations of
      superfund sites, toxic release inventory sites, or particular matter levels and
      CTCL case distribution. CONCLUSION: Our findings do not support an association
      between exposure to environmental toxins and CTCL. CTCL cases clustered in areas
      with the highest population density, which also happen to include a regional CTCL
      center. To evaluate a possibility of urban pollutants playing a role in etiology
      of CTCL, dermatologist density and access to care need to be addressed as
      potential confounders in the future studies.

PMID- 25046455
TI  - Dermatology on instagram.
AB  - The novel photo-sharing social networking platform, Instagram, has an impressive
      following of 75 million daily users, with a predominantly younger and female
      demographic. This study investigated the presence of dermatology-related content
      on Instagram. The most popular professional dermatological organizations,
      dermatology journals, and dermatology related patient advocate groups on Facebook
      and Twitter, determined from a prior study, were searched for established
      profiles on Instagram. In addition, dermatology-related terms (i.e. dermatology,
      dermatologist, alopecia, eczema, melanoma, psoriasis, and skin cancer) and
      dermatology-related hashtags (i.e. #dermatology, #dermatologist, #melanoma,
      #acne, #psoriasis, and #alopecia) were searched. None of the top ten
      dermatological journals or professional dermatological organizations were found
      on Instagram. Although only one of the top ten patient advocate groups related to
      dermatology conditions, Melanoma Research Foundation, had an Instagram presence,
      there were many private offices, cosmetic products, and some patient advocacy
      groups. This novel social networking platform could grant dermatology journals
      and other professional organizations a unique opportunity to reach younger
      demographic populations, particularly women, with the potential for true
      educational and life-changing impact. 

PMID- 25046456
TI  - Topical treatments of skin pain: a general review with a focus on hidradenitis
      suppurativa with topical agents.
AB  - Hidradenitis Supprurativa (HS) is a painful chronic follicular disease. Few
      papers have addressed pain control for this debilitating condition. Possible
      topical agents include tricyclic antidepressants, opioids, anticonvulsants,
      NSAIDs, NMDA receptor antagonists, local anesthetics and other agents. The first
      line agents for the topical treatment of the cutaneous pain of HS are diclonefac
      gel 1% and liposomal xylocaine 4% and 5% cream or 5% ointment. The chief
      advantage of topical xylocaine is that is quick acting i.e. immediate however
      with a limited duration of effect 1-2 hours. The use of topical ketamine, which
      blocks n-methyl-D-aspartate receptors in a non-competitive fashion, might be a
      useful tool for the treatment of HS pain. Topical doxepin, which available in a
      5% commercially preparation (Zonalon(r)) , makes patients drowsy and is not
      useful for controlling the pain of HS . Doxepin is available in a 3% or 3.3%
      concentration (which causes less drowsiness) from compounding pharmacies and can
      be used in compounded analgesic preparations with positive effect. Topical
      doxepin is preferred over use of topical amitriptyline because topical doxepin is
      more effective. Nevertheless, topical amitriptyline increase of the tactile and
      mechanical nociceptive thresholds and can be used for topical pain control in
      compound mixture of analgesics . Gabapentin and pregablin can also be used
      compounded with other agents in topical analgesic preparations with positive
      topical anesthetic effect. Capsaicin is not useful for topical treatment of the
      pain of HS. Sometimes compounded of anesthetics medications such as ketamine 10%,
      bupivacaine 1%, diclofenac 3%, doxepin 3% or 3.3%, and gabapentin 6% can extend
      the duration of effect so that medication only needs to be used 2 or 3 times a
      day. Still in my experience the easiest to get and most patient requested agent
      is topical diclonefac 1% gel. 

PMID- 25046457
TI  - CD30 expression in cutaneous B-cell and post-transplant peripheral T-cell
      lymphoma: report of 2 cases.
AB  - CD30 expression is the hallmark of the cutaneous CD30+ lymphoproliferative
      disorders, lymphomatoid papulosis and anaplastic large cell lymphoma. We report
      CD30 expression in cutaneous follicle center cell lymphoma and in cutaneous post
      transplant peripheral T-cell lymphoma. Histopathologists should be aware of CD30
      expression in cutaneous lymphomas outside the realm of so-called CD30+
      lymphoproliferative disorders to avoid diagnostic errors and improper medical
      treatment. 

PMID- 25046458
TI  - Cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity.
AB  - Psoriatic plaque erosion is a rare toxic side effect of low-dose methotrexate
      (LDMTX) that has been reported during the treatment of psoriasis and described as
      a herald for impending pancytopenia. Fatalities from this have rarely been
      reported. Even rarer is methotrexate (MTX)-induced erosions of clinically normal
      skin in patients without a history of psoriasis. We report 3 rare presentations
      of MTX-induced cutaneous erosions, 2 fatalities occurring with MTX-induced
      psoriatic plaque erosions, and the sixth reported case of MTX-induced erosions
      with no prior history of psoriasis. Each were elderly patients on proton pump
      inhibitors with a history of chronic non-steroidal anti-inflammatory drug (NSAID)
      use. They all presented with acute onset of erosions after a recent change in
      their MTX dose. Pancytopenia followed in each case. Physicians' awareness of the
      sequelae in MTX-induced cutaneous erosions is imperative so MTX can be
      discontinued and treatment instituted to prevent fatal bone marrow suppression. 

PMID- 25046459
TI  - Recurrent basal cell carcinoma with intracranial invasion: a case report and
      literature review.
AB  - Basal cell carcinoma (BCC) is the most common malignancy in humans. We present a
      man with a recurrent BCC of the scalp that presented as an intracranial tumor 18
      years after original excision. 

PMID- 25046460
TI  - A rare pigmentary disorder in two non-identical siblings: Griscelli Syndrome 
      type 3.
AB  - Griscelli Syndrome (GS) is a rare autosomal recessive disorder characterized by
      pigmentary dilution of the hair and skin (partial albinism). Three different
      types (1-3) caused by mutation in three different genes have been described.
      Patients with GS type 1 have primary central nervous system dysfunction; type 2
      patients commonly develop hemophagocytic lymphohistiocytosis and type 3 patients
      present with partial albinism only. Two siblings discussed here had silvery hair,
      eyebrows and eyelashes since birth with no features suggestive of
      immunodeficiency or neurological impairment, making it an even rarer presentation
      of Griscelli Syndrome, type 3. Diagnosis was confirmed on light microscopy (LM)
      of hair shafts. Both GS1 and GS2 have been described earlier. However, extensive
      search of the literature failed to reveal a similar presentation from Indian
      origin. This is the first ever report of GS-3 in non-identical siblings from
      India. 

PMID- 25046461
TI  - Pilomatrix carcinoma: a rare cause of facial tumor.
AB  - Pilomatrix carcinoma is a rare malignant tumor that originates from hair matrix
      cells. It is not usually considered in a differential diagnosis owing to its low
      incidence. We present a case of this uncommon entity and review the literature. 

PMID- 25046462
TI  - Sclerosing lymphangitis of penis - literature review and report of 2 cases.
AB  - Sclerosing lymphangitis of the penis is a condition related to vigorous sexual
      activity, manifesting as an asymptomatic firm cord -like swelling around the
      coronal sulcus of the penis. Since, it is self-limiting, only reassurance along
      with abstinence from sexual activity are required. In addition to reporting two
      new cases, we review and discuss the medical literature for this condition. 

PMID- 25046463
TI  - Giant melanoma of the abdomen: case report and revision of the published cases.
AB  - Malignant melanoma presenting as a giant cutaneous mass is rarely observed in
      clinical practice. A few patients with giant melanoma have been reported, Herein,
      we document our experience with a patient with giant cutaneous melanoma of the
      abdomen and review the features of previously reported individuals. 

PMID- 25046464
TI  - Multifocal cutaneous alternariosis in a 70-year-old Kenyan renal transplant
      patient.
AB  - Alternaria species are a group of dematiaceous fungi that are ubiquitous in
      nature and are becoming an increasingly important cause of disease in
      immunocompromised patients. We present a case of a 70 year old renal transplant
      recipient with multiple areas of cutaneous Alternaria infections likely
      introduced during local trauma. Treatment has required a combination of systemic
      therapy and surgical excision. This case illustrates the importance of
      recognizing fungal infections with cutaneous manifestations, such as
      alternariosis, in immunosuppressed patients. 

PMID- 25046465
TI  - Striated muscle hamartoma presenting as a chin cyst in a newborn.
AB  - Striated muscle hamartoma is a rare, benign mesenchymal neoplasm that typically
      arises in the midline of a newborn patient. We report a clinically and
      histopathologically classic case of striated muscle hamartoma presenting as a
      chin cyst in a newborn female. 

PMID- 25046466
TI  - Successful treatment of facial papules with electrodessication in a patient with
      Birt-Hogg-Dube syndrome.
AB  - We report a case of a 51-year-old Hispanic female who presented with a several
      year history of multiple flesh colored papules of cosmetic concern on the nose
      and medial cheeks. Biopsies revealed fibrofolliculoma and trichodiscoma. The
      patient was referred for genetic testing and was found to be positive for the
      FLCN gene defect, confirming a diagnosis of Birt-Hogg-Dube syndrome. Further work
      up with screening renal ultrasound and CT scan of the thorax and abdomen was
      unrevealing. For treatment of these skin lesions, dermasanding was attempted
      initially with only minimal benefit. She subsequently had multiple lesions
      treated with electrodessication at a low setting and was very pleased with the
      results. Curettage was not performed and importantly, there has yet to be a
      recurrence of lesions treated with only hyfrecation. 

PMID- 25046467
TI  - Bloodroot associated eschar.
AB  - We present a case of a 60-year-old woman who, after using a blemish cream
      purchased at a health store, presented to our clinic with a large eschar on the
      right neck. The active ingredient in this cream was found to be Sanguinaria
      canadensis, a known escharotic. This substance is popularly marketed as a natural
      remedy for a host of skin diseases such as blemishes, moles, warts, skin tags,
      basal cell carcinomas, squamous cell carcinomas, actinic keratoses, and even
      melanoma. The patient was treated with topical corticosteroids but is still left
      with a scar from the healed eschar. Dermatologists must be aware of the
      increasing popularity of "natural" medicinal skin cancer therapies, such as
      bloodroot-containing "cancer salves" and "herbal cures," and emphasize to their
      patients that conventional excision, micrographic surgery, electrodessication,
      and/or curettage are highly successful treatments for most skin cancers with
      little morbidity. 

PMID- 25046468
TI  - Rapidly growing pigmented tumor on a scalp nevus sebaceous of a pediatric
      patient: Observation or excision.
AB  - A 14-year-old girl presented with a new, rapidly growing, pigmented tumor on a
      previously existing yellowish, verrucous plaque on the scalp. The patient
      received complete surgical excision. Routine histology ruled out basal cell
      carcinoma (BCC) and the histological diagnosis was pigmented trichoblastoma
      arising in nevus sebaceous (NS). It is important to define management for new
      lesions developing in pediatric patients with existing nevus sebaceus. 

PMID- 25046469
TI  - Sclerotic atrophic plaques associated with a tattoo.
AB  - Lichen sclerosus is a chronic inflammatory disease, usually of the anogenital
      area, that causes intractable itching and soreness. Less commonly, it may have
      extragenital involvement in 15 to 20% of cases. Lichen sclerosus has been
      reported at sites of injury as a Koebner phenomenon. We report a case of lichen
      sclerosus at the site of a tattoo with simultaneous genital involvement. 

PMID- 25046470
TI  - Chronic myelomonocytic leukemia can present with diffuse planar xanthoma.
AB  - There is a documented association between diffuse planar xanthoma and chronic
      myelomonocytic leukemia. Previous accounts have hypothesized that patients with
      multiple lesions or extensive cutaneous disease are more likely to have an
      underlying abnormality of the reticuloendothelial system. However, we document a
      62-year-old woman with a large pruritic yellow-orange plaque on the chest and
      lower anterior neck consistent with planar xanthoma that was discovered to have
      chronic myelomonocytic leukemia. Solitary large plaques of planar xanthoma should
      be considered in the same fashion as diffuse planar xanthoma and warrant a prompt
      hematologic evaluation. 

PMID- 25046471
TI  - Purplish tender nodule on the arm.
AB  - We present a patient with a painful glomus tumor of the right upper arm. 

PMID- 25046472
TI  - Triple D Score is a reportable predictor of shockwave lithotripsy stone-free
      rates.
AB  - PURPOSE: Over the last decade, shockwave lithotripsy (SWL) success rates have
      been correlated with stone density, skin-to-stone distance (SSD), and stone
      diameter. However, time constraints and the technical challenge of manual
      measurement often preclude utilization of these parameters. In this study, we
      describe a scoring system that accurately predicts SWL stone-free rates, is
      simple to calculate, and can be easily included in the radiology report.
      MATERIALS AND METHODS: Two hundred thirty-five patients who underwent SWL from
      2011 to 2014 were evaluated. One hundred thirty-three had available preoperative
      imaging. Stone density, SSD, ellipsoid stone volume (ESV), and stone-free rates
      were determined. Receiver operator characteristic (ROC) curves were generated to
      determine cutoff values for each parameter. The Triple D Score was calculated
      based upon the number of cutoff values a stone fell below. RESULTS: One hundred
      forty of the 235 patients (59.5%) who underwent SWL were stone free after single
      session treatment. Seventy-six of the 133 (57.1%) patients with available
      preoperative imaging were stone free. ESV, SSD, and stone density were
      significant predictors of SWL success. Based upon the ROC curves, cutoffs of <150
      MUL for ESV, <12 cm for SSD, and <600 HU for stone density were established. A
      Triple D Score of 0, 1, 2, and 3 correlated with SWL success rates of 21.4%,
      41.3%, 78.7%, and 96.1%, respectively. CONCLUSIONS: Readily available predictive
      tools are necessary to enhance SWL cost-effectiveness. The Triple D Score is
      simple to calculate and can be reported by radiologists. Incorporation of the
      Triple D Score into preoperative planning may increase the overall SWL success
      rates.

PMID- 25046473
TI  - Field validation of food outlet databases: the Latino food environment in North
      Carolina, USA - ERRATUM.

PMID- 25046474
TI  - Synthesis of aromatic sphingosine analogues by diastereoselective amination of
      enantioenriched trans-gamma,delta-unsaturated beta-hydroxyesters.
AB  - An effective route to N-Boc-protected aromatic sphingosine analogues is
      accomplished. The strategy is based on the diastereoselective amination of
      enantioenriched trans-gamma,delta-unsaturated beta-hydroxyesters to establish
      anti,N-Boc-alpha-hydrazino-beta-hydroxyesters. Nonreductive E1cB elimination is
      essential for the successful N-N bond cleavage of hydrazine while preserving the
      trans double bond. Either the (3R,2S) and (3S,2R) enantiomer of N-Boc-protected
      sphingosine analogues has been synthesized in five steps with excellent optical
      purity with ~99% ee and >99% de. 

PMID- 25046475
TI  - C5-symmetric chiral corannulenes: desymmetrization of bowl inversion equilibrium
      via "intramolecular" hydrogen-bonding network.
AB  - Because of a rapid conformational inversion, bowl-shaped C5-symmetric
      corannulenes, though geometrically chiral, have not been directly resolved into
      their enantiomers. However, if this inversion equilibrium can be desymmetrized,
      chiral corannulenes enriched in either enantiomer can be obtained. We
      demonstrated this possibility using pentasubstituted corannulenes 4 and 5
      carrying amide-appended thioalkyl side chains. Compound 4 displays chiroptical
      activity in a chiral hydrocarbon such as limonene. Because compound 5 carries a
      chiral center in the side chains, its enantiomers 5R and 5S show chiroptical
      activity even in achiral solvents such as CHCl3 and methylcyclohexane. In sharp
      contrast, when the side chains bear no amide functionality (1 and 2R), no
      chiroptical activity emerges even in limonene or with a chiral center in the side
      chains. Detailed investigations revealed that the peripheral amide units in 4 and
      5 are hydrogen-bonded only "intramolecularly" along the corannulene periphery,
      affording cyclic amide networks with clockwise and anticlockwise geometries.
      Although this networking gives rise to four stereoisomers, only two, which are
      enantiomeric to one another, are suggested computationally to exist in the
      equilibrated system. In a chiral environment (chiral solvent or side chain),
      their thermodynamic stabilities are certainly unequal, so the bowl-inversion
      equilibrium can be desymmetrized. However, this is not the case when the system
      contains a protic solvent that can deteriorate the hydrogen-bonding network. When
      the enantiomeric purity of limonene as the solvent is varied, the chiroptical
      activity of the corannulene core changes nonlinearly with its enantiomeric excess
      (majority rule). 

PMID- 25046476
TI  - Molecular insights into the electric double layers of ionic liquids on Au(100)
      electrodes.
AB  - The electric double layer structure and differential capacitance of single
      crystalline Au(100) electrodes in the ionic liquid 1-butyl-3-methyl-imidazolium
      hexafluorophosphate are investigated using molecular dynamics simulations.
      Results show strong adsorption on the electrode surface. The potential of zero
      charge (pzc) and maxima of differential capacitance are strongly dependent on the
      adsorption layer structure. At potentials near the pzc, cations and anions
      adjacent to the electrode surface are coadsorbed on the same screening layer.
      This strong adsorption layer results in overscreening effects on the compact
      layer and induces both a bell-shaped differential capacitance curve and a
      positive pzc. Moreover, the potential required for transition from overscreening
      to overcrowding is about 4.0 V. This transition potential may be attributed to
      the higher interaction energy between the Au(100) electrode and ions compared
      with the binding energy in our cation-anion system. 

PMID- 25046477
TI  - Polymer-grafted lignin surfactants prepared via reversible addition-fragmentation
      chain-transfer polymerization.
AB  - Kraft lignin grafted with hydrophilic polymers has been prepared using reversible
      addition-fragmentation chain-transfer (RAFT) polymerization and investigated for
      use as a surfactant. In this preliminary study, polyacrylamide and poly(acrylic
      acid) were grafted from a lignin RAFT macroinitiator at average initiator site
      densities estimated to be 2 per particle and 17 per particle. The target degrees
      of polymerization were 50 and 100, but analysis of cleaved polyacrylamide was
      consistent with a higher average molecular weight, suggesting not all sites were
      able to participate in the polymerization. All materials were readily soluble in
      water, and dynamic light scattering data indicate polymer-grafted lignin
      coexisted in isolated and aggregated forms in aqueous media. The characteristic
      size was 15-20 nm at low concentrations, and aggregation appeared to be a
      stronger function of degree of polymerization than graft density. These species
      were surface active, reducing the surface tension to as low as 60 dyn/cm at 1
      mg/mL, and a greater decrease was observed than for polymer-grafted silica
      nanoparticles, suggesting that the lignin core was also surface active. While
      these lignin surfactants were soluble in water, they were not soluble in hexanes.
      Thus, it was unexpected that water-in-oil emulsions formed in all surfactant
      compositions and solvent ratios tested, with average droplet sizes of 10-20 MUm.
      However, although polymer-grafted lignin has structural features similar to
      nanoparticles used in Pickering emulsions, its interfacial behavior was
      qualitatively different. While at air-water interfaces, the hydrophilic grafts
      promote effective reductions in surface tension, we hypothesize that the low
      grafting density in these lignin surfactants favors partitioning into the hexanes
      side of the oil-water interface because collapsed conformations of the polymer
      grafts improve interfacial coverage and reduce water-hexanes interactions. We
      propose that polymer-grafted lignin surfactants can be considered as random
      patchy nanoparticles with mixed hydrophilic and hydrophobic domains that result
      in unexpected interfacial behaviors. Further studies are necessary to clarify the
      molecular basis of these phenomena, but grafting of hydrophilic polymers from
      kraft lignin via radical polymerization could expand the use of this important
      biopolymer in a broad range of surfactant applications. 

PMID- 25046478
TI  - Exploring the spectrum of diseases influenced by excess adiposity.

PMID- 25046479
TI  - Photo-responsive polymeric micelles.
AB  - Photo-responsive polymeric micelles have received increasing attention in both
      academic and industrial fields due to their efficient photo-sensitive nature and
      unique nanostructure. In view of the photo-reaction mechanism, photo-responsive
      polymeric micelles can be divided into five major types: (1) photoisomerization
      polymeric micelles, (2) photo-induced rearrangement polymeric micelles, (3)
      photocleavage polymeric micelles, (4) photo-induced crosslinkable polymeric
      micelles, and (5) photo-induced energy conversion polymeric micelles. This review
      highlights the recent advances of photo-responsive polymeric micelles, including
      the design, synthesis and applications in various biomedical fields. Especially,
      the influence of different photo-reaction mechanisms on the morphology, structure
      and properties of the polymeric micelles is emphasized. Finally, the possible
      future directions and perspectives in this emerging area are briefly discussed. 

PMID- 25046480
TI  - beta,gamma-Regioselective inverse-electron-demand aza-Diels-Alder reactions with
      alpha,beta-unsaturated aldehydes via dienamine catalysis.
AB  - A stereoselective inverse-electron-demand aza-Diels-Alder cycloaddition process
      of cyclic 1-aza-1,3-butadienes and alpha,beta-unsaturated aldehydes has been
      developed via dienamine catalysis. This reaction exhibits excellent beta,gamma
      regioselectivity for enal substrates with substantial structural diversity and
      broad functionalities, readily producing highly enantioenriched fused piperidine
      derivatives and enabling efficient sequential construction of complex polycyclic
      frameworks. 

PMID- 25046482
TI  - Evaluation of different mathematical models for diffusion-weighted imaging of
      normal prostate and prostate cancer using high b-values: a repeatability study.
AB  - PURPOSE: To evaluate monoexponential, stretched exponential, kurtosis, and
      biexponential models for diffusion-weighted imaging (DWI) of normal prostate and
      prostate cancer (PCa), using b-values up to 2000 s/mm(2) , in terms of fitting
      quality and repeatability. METHODS: Eight healthy volunteers and 16 PCa patients
      underwent a total of four repeated 3T DWI examinations using 16 and 12 b-values,
      respectively. The highest b-value was 2000 s/mm(2) . The normalized mean signal
      intensities of regions of interest, placed in normal tissue and PCa using
      anatomical images and prostatectomy sections, were fitted using the four models.
      The fitting quality was evaluated using Akaike information criteria and F-ratio.
      Repeatability of the fitted parameters was evaluated using intraclass correlation
      coefficient ICC(3,1). RESULTS: The biexponential model provided the best fit to
      normal prostate and PCa DWI data. The parameters of the monoexponential,
      kurtosis, and stretched exponential (with the exception of the alpha parameter)
      models had higher ICC(3,1) values compared with the biexponential model. The
      kurtosis model provided a better fit to DWI data of normal prostate and PCa than
      the monoexponential model, whereas these models had comparable reliability and
      repeatability based on ICC(3,1) values. CONCLUSION: Considering the model fit and
      repeatability, the kurtosis model seems to be the preferred model for
      characterization of normal prostate and PCa DWI using b-values up to 2000 s/mm(2)
      .

PMID- 25046481
TI  - A model for extra-axonal diffusion spectra with frequency-dependent restriction.
AB  - PURPOSE: In the brain, there is growing interest in using the temporal diffusion
      spectrum to characterize axonal geometry in white matter because of the potential
      to be more sensitive to small pores compared to conventional time-dependent
      diffusion. However, analytical expressions for the diffusion spectrum of
      particles have only been derived for simple, restricting geometries such as
      cylinders, which are often used as a model for intra-axonal diffusion. The extra
      axonal space is more complex, but the diffusion spectrum has largely not been
      modeled. We propose a model for the extra-axonal space, which can be used for
      interpretation of experimental data. THEORY AND METHODS: An empirical model
      describing the extra-axonal space diffusion spectrum was compared with simulated
      spectra. Spectra were simulated using Monte Carlo methods for idealized,
      regularly and randomly packed axons over a wide range of packing densities and
      spatial scales. The model parameters are related to the microstructural
      properties of tortuosity, axonal radius, and separation for regularly packed
      axons and pore size for randomly packed axons. RESULTS: Forward model predictions
      closely matched simulations. The model fitted the simulated spectra well and
      accurately estimated microstructural properties. CONCLUSIONS: This simple model
      provides expressions that relate the diffusion spectrum to biologically relevant
      microstructural properties.

PMID- 25046483
TI  - Association between cardiovascular vs. non-cardiovascular co-morbidities and
      outcomes in heart failure with preserved ejection fraction.
AB  - AIMS: The prevalence of cardiovascular and non-cardiovascular co-morbidities and
      their relative importance for outcomes in heart failure with preserved ejection
      fraction (HFPEF) remain poorly characterized. This study aimed to investigate
      this. METHODS AND RESULTS: The Karolinska-Rennes (KaRen) Study was a
      multinational prospective observational study designed to characterize HFPEF.
      Inclusion required acute HF, defined by the Framingham criteria, LVEF >= 45%, and
      NT-pro-BNP >= 300 ng/L or BNP >= 100 ng/L. Detailed clinical data were collected
      at baseline and patients were followed prospectively for 18 months. Predictors of
      the primary (HF hospitalization or all-cause mortality) and secondary (all-cause
      mortality) outcomes were assessed with multivariable Cox regression. A total of
      539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT
      pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of
      HF was present in 40%. Co-morbidities included hypertension (78%), atrial
      fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%),
      diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome
      occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations
      (30%)]. Important independent predictors of the primary and/or secondary outcomes
      were age, history of non-cardiovascular syncope, valve disease, anaemia, lower
      sodium, and higher potassium, but no cardiovascular co-morbidities. Renin
      angiotensin system antagonist and mineralocorticoid receptor antagonist use
      predicted improved prognosis. CONCLUSION: HFPEF was associated with higher age,
      female gender, hypertension, atrial fibrillation/flutter, and numerous non
      cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co
      morbidities, but use of conventional heart failure medications may still be
      associated with improved outcomes.

PMID- 25046484
TI  - Aqueous two-phase system-mediated antibody micropatterning enables multiplexed
      immunostaining of cell monolayers and tissues.
AB  - Conventional immunostaining methods consume large quantities of expensive
      antibodies and are limited in terms of the number of antigens that can be
      detected from a single sample. In order to achieve multiplexed immunostaining, we
      micropatterned antibodies using aqueous two-phase systems (ATPS) formed from
      polyethylene glycol (PEG) and dextran. Multiple antigens can be detected on a
      single fixed sample by incorporating antibodies within dextran solutions, which
      are then patterned by micropipetting at specific sites on the sample in a
      solution of PEG. The antibodies are retained within the dextran phase due to
      biomolecular partitioning, allowing multiple protein markers to be visualized
      simultaneously by way of chromogenic, chemiluminescent, or immunofluorescent
      detection. This aqueous two-phase system-mediated antibody micropatterning
      approach allows antibody dilutions to be easily optimized, reduces the
      consumption of expensive primary antibodies and can prevent antibody cross
      reactions, since the antibodies are retained at separate sites within the dextran
      microdroplets.

PMID- 25046485
TI  - Potential novel role of bevacizumab in glioblastoma and cervical cancer.
AB  - The VEGF-A binding monoclonal antibody bevacizumab is a widely prescribed
      angiogenesis inhibitor and indicated for many types of cancer. As shown by three
      randomized phase 3 trials recently published in the New England Journal of
      Medicine, novel indications for this drug are still being explored. In the RTOG
      0825 and AVAglio trials the effect of bevacizumab addition to standard therapy in
      newly diagnosed glioblastoma (radiotherapy plus temozolomide) was investigated,
      while in GOG 240 the combination of platinum-based chemotherapy plus bevacizumab
      was explored in advanced cervical cancer. In RTOG 0825, addition of bevacizumab
      to standard therapy did not result in survival benefit, and moreover, quality of
      life was more deteriorated in the bevacizumab arm. In AVAglio, however,
      progression-free survival (PFS) was significantly increased in the bevacizumab
      group and these patients also experienced a longer deterioration-free survival.
      These conflicting results do not fully support the incorporation of bevacizumab
      in the first-line treatment of glioblastoma. In contrast, in GOG 240 the
      bevacizumab group (including paclitaxel plus topotecan or paclitaxel) experienced
      a significant longer PFS and overall survival, and quality of life was not
      negatively affected in these patients. Thus, these results favor the use of
      bevacizumab in the treatment of advanced cervical cancer. 

PMID- 25046486
TI  - Kinome siRNA screen identifies novel cell-type specific dengue host target genes.
AB  - Dengue is a global emerging infectious disease, with no specific treatment
      available. To identify novel human host cell targets important for dengue virus
      infection and replication, an image-based high-throughput siRNA assay screening
      of a human kinome siRNA library was conducted using human hepatocyte cell line
      Huh7 infected with a recent dengue serotype 2 virus isolate BR DEN2 01-01. In the
      primary siRNA screening of 779 kinase-related genes, knockdown of 22 genes showed
      a reduction in DENV-2 infection. Conversely, knockdown of 8 genes enhanced viral
      infection. To assess host cell specificity, the confirmed hits were tested in the
      DENV-infected monocytic cell line U937. While the expression of EIF2AK3, ETNK2
      and SMAD7 was regulated in both cell lines after infection, most kinases were
      hepatocyte-specific. Monocytic cells represent initial targets of infection and
      an antiviral treatment targeting these cells is probably most effective to reduce
      initial viral load. In turn, infection of the liver could contribute to
      pathogenesis, and the novel hepatocyte-specific human targets identified here
      could be important for dengue infection and pathogenesis. 

PMID- 25046489
TI  - A better way to track medical device experiences.

PMID- 25046488
TI  - In times of trouble.

PMID- 25046493
TI  - Ten questions with .... Paul Coss.

PMID- 25046496
TI  - Ask George.

PMID- 25046497
TI  - Clearing the air: innovations and complications with ventilator technology.

PMID- 25046498
TI  - Sharing the monkey at work.

PMID- 25046499
TI  - How clean is clean?: chemistry can damage medical equipment in the quest to meet
      stringent guidelines.

PMID- 25046500
TI  - A postmarket surveillance benchmarking exercise.

PMID- 25046501
TI  - Workplace crises: keys to prevention and planning.

PMID- 25046502
TI  - A deep dive into EC.02.03.05: maintaining fire equipment and building features.

PMID- 25046503
TI  - Quality officer takes on patient safety challenges.

PMID- 25046504
TI  - From disarray to shipshape: implementing an e-library.

PMID- 25046505
TI  - Data integrity: the cornerstone of any quality HTM program.

PMID- 25046506
TI  - 'No problem found' service calls--keep digging.

PMID- 25046507
TI  - The fundamentals of...bone densitometry.

PMID- 25046508
TI  - Heavy lifting: what to do when patient lifts aren't up to the task.

PMID- 25046510
TI  - Don't get zapped by rule on extension cords, outlets.

PMID- 25046511
TI  - Challenges to validation of a complex nonsterile medical device tray.
AB  - Validation by steam sterilization of reusable medical devices requires careful
      attention to many parameters that directly influence whether or not complete
      sterilization occurs. Complex implant/instrument tray systems have a variety of
      configurations and components. Geobacillus stearothermophilus biological
      indicators (BIs) are used in overkill cycles to to simulate worst case conditions
      and are intended to provide substantial sterilization assurance. Survival of G.
      stearothermophilus spores was linked to steam access and size of load in the
      chamber. By a small and reproducible margin, it was determined that placement of
      the trays in a rigid container into minimally loaded chambers were more difficult
      to completely sterilize than maximally loaded chambers. 

PMID- 25046512
TI  - The need for formal education is on the rise.

PMID- 25046514
TI  - Exome sequencing for gene discovery in lethal fetal disorders--harnessing the
      value of extreme phenotypes.
AB  - Massively parallel sequencing has revolutionized our understanding of Mendelian
      disorders, and many novel genes have been discovered to cause disease phenotypes
      when mutant. At the same time, next-generation sequencing approaches have enabled
      non-invasive prenatal testing of free fetal DNA in maternal blood. However,
      little attention has been paid to using whole exome and genome sequencing
      strategies for gene identification in fetal disorders that are lethal in utero,
      because they can appear to be sporadic and Mendelian inheritance may be missed.
      We present challenges and advantages of applying next-generation sequencing
      approaches to gene discovery in fetal malformation phenotypes and review recent
      successful discovery approaches. We discuss the implication and significance of
      recessive inheritance and cross-species phenotyping in fetal lethal conditions.
      Whole exome sequencing can be used in individual families with undiagnosed lethal
      congenital anomaly syndromes to discover causal mutations, provided that prior to
      data analysis, the fetal phenotype can be correlated to a particular
      developmental pathway in embryogenesis. Cross-species phenotyping allows
      providing further evidence for causality of discovered variants in genes involved
      in those extremely rare phenotypes and will increase our knowledge about normal
      and abnormal human developmental processes. Ultimately, families will benefit
      from the option of early prenatal diagnosis.

PMID- 25046516
TI  - Computational and ion mobility MS study of (all-S)-cyclohexylhemicucurbit[6]uril
      structure and complexes.
AB  - A computational study of (all-S)-cyclohexylhemicucurbit[6]uril and its complexes
      with anions (Cl(-), Br(-), I(-) and HCOO(-)), the proton (H(+)) and non
      dissociated acid (HCl, HBr, HI and HCOOH) guests was performed. The geometries of
      guest-host complexes were optimized via density functional theory using the BP86
      functional, SV(P) basis set and Stuttgart pseudopotentials for iodide. Binding
      affinities and their trends were evaluated at the BP86/TZVPD level of theory. In
      addition, the quantum theory of atoms in molecules was used to gain insight into
      guest-host interactions. A computational study in the gas phase and ion-mobility
      mass-spectrometry analysis revealed that the studied macrocycle formed inclusion
      complexes with anions. Protonation of the macrocycle is preferred at the nitrogen
      atom pointing inside of the cavity. In the studied conditions, non-dissociated
      acids formed complexes at the oxygen atom pointing outside of the macrocycle. 

PMID- 25046515
TI  - Improvements in concentration, working memory and sustained attention following
      consumption of a natural citicoline-caffeine beverage.
AB  - This study examined the neurocognitive and electrophysiological effects of a
      citicoline-caffeine-based beverage in 60 healthy adult participants enrolled in a
      randomized, double-blind, placebo-controlled trial. Measures of electrical brain
      activity using electroencephalogram (EEG) and neuropsychological measures
      examining attention, concentration and reaction time were administered. Compared
      to placebo, participants receiving the citicoline-caffeine beverage exhibited
      significantly faster maze learning times and reaction times on a continuous
      performance test, fewer errors in a go/no-go task and better accuracy on a
      measure of information processing speed. EEG results examining P450 event-related
      potentials revealed that participants receiving the citicoline-caffeine beverage
      exhibited higher P450 amplitudes than controls, suggesting an increase in
      sustained attention. Overall, these findings suggest that the beverage
      significantly improved sustained attention, cognitive effort and reaction times
      in healthy adults. Evidence of improved P450 amplitude indicates a general
      improvement in the ability to accommodate new and relevant information within
      working memory and overall enhanced brain activation.

PMID- 25046517
TI  - Group A streptococcus and host metabolism: virulence influences and potential
      treatments.

PMID- 25046518
TI  - Are we close to a vaccination against Staphylococcus aureus?

PMID- 25046520
TI  - Evaluation of different microtiter plate-based methods for the quantitative
      assessment of Staphylococcus aureus biofilms.
AB  - AIM: To quantitatively assess Staphylococcus aureus biofilms. MATERIALS &
      METHODS: In addition to the qualitative Congo red agar (CRA) method, we used the
      bioluminescence (BLM), safranine (SAF), crystal violet (CRV) and resazurin (RES)
      high-throughput microtiter plate-based quantitative assays. RESULTS: 60.47%
      (26/43) of S. aureus clinical isolates were weak biofilm producers. The CRA
      method detected positive-slime phenotypes (13.95%), but was unable to distinguish
      weak from negative producers. BLM assays demonstrated significant correlations
      with RES (highest), CRV and SAF (lowest). Lower coefficient of variation values
      indicate precision. BLM scored highest precision (coefficient of variation =
      0.013) followed by RES, SAF and CRV. CONCLUSION: BLM and RES detect live biomass
      in S. aureus biofilms (for physiological studies). SAF and CRV detect live/dead
      bacteria plus biofilm matrix (for monitoring overall biofilm architecture, not
      only its cell viability). Reliable assays are essential for effective biofilm
      therapy.

PMID- 25046521
TI  - Fusidic acid resistance in Staphylococcus aureus nasal carriage strains in nine
      European countries.
AB  - AIM: To evaluate fusidic acid resistance pheno- and geno-typically in nasal
      carriage Staphylococcus aureus isolated from general practice patients in nine
      European countries. MATERIALS & METHODS: Phenotypic fusidic acid resistance was
      determined by disc diffusion and MIC values, and genotypically by a PCR detecting
      fusA-E genes. The main analysis was performed on methicillin-susceptible S.
      aureus strains, because methicillin-resistant S. aureus isolates were scarce.
      RESULTS: Overall S. aureus fusidic acid resistance was low (<10%). fusC was the
      predominant mechanism of resistance and associations were found between
      resistance genes and specific spa types. CONCLUSION: S. aureus strains showed low
      resistance to fusidic acid, making this antibiotic an appropriate choice in the
      treatment of methicillin-susceptible S. aureus skin infections in general
      practice patients in the nine participating European countries.

PMID- 25046522
TI  - Role of epigenetics in EBV regulation and pathogenesis.
AB  - Epigenetic modifications of the viral and host cell genomes regularly occur in
      EBV-associated lymphomas and carcinomas. The cell type-dependent usage of latent
      EBV promoters is determined by the cellular epigenetic machinery. Viral
      oncoproteins interact with the very same epigenetic regulators and alter the
      cellular epigenotype and gene-expression pattern: there are common gene sets
      hypermethylated in both EBV-positive and EBV-negative neoplasms of different
      histological types. A group of hypermethylated promoters may represent, however,
      a unique EBV-associated epigenetic signature in EBV-positive gastric carcinomas.
      By contrast, EBV-immortalized B-lymphoblastoid cell lines are characterized by
      genome-wide demethylation and loss and rearrangement of heterochromatic histone
      marks. Early steps of EBV infection may also contribute to reprogramming of the
      cellular epigenome.

PMID- 25046523
TI  - Improved treatment of multidrug-resistant bacterial infections: utility of
      clinical studies.
AB  - In a time of increasing antibacterial resistance and limited availability of new
      antibiotics, clinical studies are much needed to assess treatment options against
      multidrug-resistant organisms (MDROs). In this review, we describe the clinical
      challenge caused by MDROs and present recent evidence on how clinical studies may
      generate quality data to improve antibiotic treatment of MDRO infections. To this
      aim, we critically assess the current status, gaps and challenges associated with
      observational and interventional studies performed to assess MDRO treatment
      options. We address why observational studies are useful, which treatment options
      for MDRO have been explored by observational studies and how to improve quality
      and usefulness of observational studies. Furthermore, the utility of clinical
      pharmacokinetic/pharmacodynamic studies for improving MDRO treatment is
      described. Finally, we discuss interventional study designs, end points and
      margins, as well as ethical, logistic and statistical challenges, and current
      regulatory changes proposed to foster the development of new antibiotics. 

PMID- 25046524
TI  - Combination therapy in severe Acinetobacter baumannii infections: an update on
      the evidence to date.
AB  - Acinetobacter baumannii is a drug-resistant Gram-negative pathogen increasingly
      causing hospital-acquired infections in critically ill patients. In this review,
      we summarize the current mechanisms of antimicrobial resistance in A. baumannii
      and describe in detail recent in vitro and in vivo experimental data on the
      activity of antimicrobial combinations against this microorganism. We then
      introduce the rationale for the use of combination antibiotic therapy in
      resistant A. baumannii infections. Finally, we present and critically discuss
      both uncontrolled clinical studies and the few randomized clinical trials of
      combination antimicrobial therapy for these infections, with a special focus on
      ongoing multinational trials and optimal approach to future research in this
      field. 

PMID- 25046526
TI  - Mother-to-child transmission of mutans streptococci.
AB  - Mutans streptococci (MS) are the major group of pathogens implicated in dental
      caries. Like other infectious diseases, transmission of the causative
      microorganisms is the initial and essential step that should be understood
      relative to disease control and prevention. This review summarizes current
      knowledge regarding MS transmission, especially from mothers to their children.
      Included are methods used to study transmission, sources of MS, initial
      acquisition, factors concerning transmission and prevention of transmission.
      Information accumulated over many decades showed the involvement of MS
      transmission in the pathogenesis of caries, hence several preventive measurements
      have been proposed. Nevertheless, some essential aspects remain to be elucidated
      for more benefits of practical application. 

PMID- 25046527
TI  - Surface complexation of antimony on kaolinite.
AB  - Geochemical fate of antimony (Sb) - a similar oxyanion as arsenic (As) - in a
      variety of environment is largely unexplored. Kaolinite is an important,
      naturally occurring clay mineral in soils and aquifers and is known to control
      the fate of several contaminants via a multitude of geochemical processes,
      primarily adsorption. Here we report adsorption of antimony on kaolinite as a
      function of solution chemistry: initial antimony concentration, pH, ionic
      strength, and a competing anion. A surface complexation modeling (SCM) approach
      was undertaken to understand the potential mechanistic implications of sorption
      envelope data. In the SCM, a multicomponent additive approach, in which kaolinite
      is assumed to be a (1:1) mixture of quartz (=SiOH) and gibbsite (=AlOH), was
      tested. Results indicated that ionic strength has a minimal effect on antimony
      adsorption. For the lower initial antimony concentration (4.11 MUM), the additive
      model with binuclear surface complexes on quartz and gibbsite showed a better fit
      at pH<6, but somewhat under predicted the experimental data above pH 6. At the
      higher initial antimony concentration (41.1 MUM), the sorption envelope was of
      different shape than the lower load. The additive model, which considered
      binuclear surface complexes for quartz and gibbsite, resulted in over prediction
      of the adsorption data at pH>3.5. However, the additive model with binuclear
      surface complex on quartz and mononuclear surface complex on gibbsite showed an
      excellent fit of the data. Phosphate greatly influenced antimony adsorption on
      kaolinite at both low and high antimony loadings, indicating competition for
      available surface sites.

PMID- 25046525
TI  - Antifungal drug discovery: the process and outcomes.
AB  - New data suggest that the global incidence of several types of fungal diseases
      have traditionally been under-documented. Of these, mortality caused by invasive
      fungal infections remains disturbingly high, equal to or exceeding deaths caused
      by drug-resistant tuberculosis and malaria. It is clear that basic research on
      new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we
      focus upon antifungal drug discovery including in vitro assays, compound
      libraries and approaches to target identification. Genome mining has made it
      possible to identify fungal-specific targets; however, new compounds to these
      targets are apparently not in the antimicrobial pipeline. We suggest that
      'repurposing' compounds (off patent) might be a more immediate starting point.
      Furthermore, we examine the dogma on antifungal discovery and suggest that a
      major thrust in technologies such as structural biology, homology modeling and
      virtual imaging is needed to drive discovery.

PMID- 25046528
TI  - Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome
      inhibitor to human pancreatic cancer cells.
AB  - The aim of this study was to develop a drug delivery system based on poly(lactic
      co-glycolic acid) (PLGA) nanoparticles for an efficient and targeted action of
      the proteasome inhibitor bortezomib against pancreatic cancer cells. The PLGA
      nanoparticles were formulated with a poloxamer, and further surface-modified with
      transferrin for tumor targeting. The nanoparticles were characterized as polymer
      carriers of bortezomib, and the cellular uptake and growth inhibitory effects
      were evaluated in pancreatic cells. Cellular internalization of nanoparticles was
      observed in normal and cancer cells, but with higher uptake by cancer cells. The
      sustained release of the loaded bortezomib from PLGA nanoparticles showed
      cytotoxic effects against pancreatic normal and cancer cells. Noteworthy
      differential cytotoxicity was attained by transferrin surface-modified PLGA
      nanoparticles since significant cell growth inhibition by delivered bortezomib
      was only observed in cancer cells. These findings demonstrate that the ligand
      transferrin enhanced the targeted delivery of bortezomib-loaded PLGA
      nanoparticles to pancreatic cancer cells. These in vitro results highlight the
      transferrin surface-modified PLGA nanoparticles as a promising system for
      targeted delivery of anticancer drugs.

PMID- 25046530
TI  - Genetic deletion of MT1/MT2 melatonin receptors enhances murine cognitive and
      motor performance.
AB  - Melatonin, an indoleamine hormone secreted into circulation at night primarily by
      the brain's pineal gland, has been shown to have a wide variety of actions on the
      development and physiology of neurons in the CNS. Acting via two G-protein
      coupled membrane receptors (MT1 and MT2), melatonin modulates neurogenesis,
      synaptic functions, neuronal cytoskeleton and gene expression. In the present
      studies, we sought to characterize the behavior and neuronal biology of
      transgenic mice lacking both of these melatonin receptors as a way to understand
      the hormone's receptor versus non-receptor-mediated actions in CNS-dependent
      activities, such as learning and memory, anxiety, general motor performance and
      circadian rhythmicity. Assessment of these behaviors was complemented by
      molecular analyses of gene expression in the brain. Our results demonstrate mild
      behavioral hyperactivity and a lengthened circadian period of free-running motor
      activity in melatonin receptor-deficient mice as compared to receptor-intact
      control mice beginning at an early age. Significant improvement in cognitive
      performance was found using the Barnes Maze and the Y-Maze. No behavioral changes
      in anxiety levels were found. Electrophysiological measures in hippocampal slices
      revealed a clear enhancement of long-term potentiation in mice lacking melatonin
      receptors with no significant differences in paired-pulse facilitation.
      Quantitative analysis of brain protein expression levels of phosphoCREB and
      phosphoERK1/2 and key markers of synaptic activity (synapsin, glutamate receptor
      1, spinophilin, and glutamic acid decarboxylase 1) revealed significant
      differences between the double-knockout and wild-type animals, consistent with
      the behavioral findings. Thus, genetic deletion of melatonin receptors produces
      mice with enhanced cognitive and motor performance, supporting the view that
      these receptors play an important role in neurobehavioral development. 

PMID- 25046529
TI  - Extracorporeal life support in critically ill adults.
AB  - Extracorporeal life support (ECLS) has become increasingly popular as a salvage
      strategy for critically ill adults. Major advances in technology and the severe
      acute respiratory distress syndrome that characterized the 2009 influenza A(H1N1)
      pandemic have stimulated renewed interest in the use of venovenous extracorporeal
      membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal to support
      the respiratory system. Theoretical advantages of ECLS for respiratory failure
      include the ability to rest the lungs by avoiding injurious mechanical ventilator
      settings and the potential to facilitate early mobilization, which may be
      advantageous for bridging to recovery or to lung transplantation. The use of
      venoarterial ECMO has been expanded and applied to critically ill adults with
      hemodynamic compromise from a variety of etiologies, beyond postcardiotomy
      failure. Although technology and general care of the ECLS patient have evolved,
      ECLS is not without potentially serious complications and remains unproven as a
      treatment modality. The therapy is now being tested in clinical trials, although
      numerous questions remain about the application of ECLS and its impact on
      outcomes in critically ill adults. 

PMID- 25046531
TI  - Modeling of regulatory loops controlling galactolipid biosynthesis in the inner
      envelope membrane of chloroplasts.
AB  - In Angiosperms, the biosynthesis of galactolipids involves enzymes localized in
      the inner envelope membrane (IEM) of chloroplasts, including a phosphatidic acid
      phosphatase (PAP), dephosphorylating phosphatidic acid (PA) into diacylglycerol
      (DAG), and MGD1, transferring a galactose onto DAG thus generating
      monogalactosyldiacylglycerol (MGDG). It has been shown that PA and DAG could be
      synthesized in the plastid via the so-called 'prokaryotic' pathway or imported
      from the endoplasmic reticulum via the 'eukaryotic' pathway. In vitro studies
      support the existence of (1) a negative regulation of the plastid PAP by DAG and
      (2) an activation of MGD1 by PA. We developed a mathematical model of the IEM
      galactolipid biosynthesis pathway to understand the properties of the system
      ruled by the presence of these two regulatory motifs. We demonstrated that the
      design of the system implies that PA should accumulate to levels that are not
      observed experimentally, regardless of its prokaryotic or eukaryotic origin. PA
      should therefore be used for other syntheses, such as that of
      phosphatidylglycerol. Whereas a massive influx of eukaryotic PA appears unlikely,
      an influx of eukaryotic DAG in the IEM is supported by simulations. The model
      also implies that DAG cannot transiently accumulate and that PA mainly acts as a
      signal switching the whole system on. Eventually, this analysis highlights the
      fact that the PAP enzyme could easily become dispensable and that the design of
      the system, with the two regulatory motifs, could precede the loss of the PAP
      gene or activity in this pathway, a phenomenon that occurred independently in
      most clades of Angiosperms. 

PMID- 25046532
TI  - Personalizing prostate cancer therapy: the way forward.
AB  - Advances in genomic sequencing and molecular characterization are improving our
      understanding of the biology of prostate cancer and challenging us to translate
      emerging data into meaningful clinical outcomes. Several recently approved
      treatments for advanced prostate cancer extend survival; however, these therapies
      are not personalized based on predictive biomarkers. Innovative strategies for
      early phase drug testing that harness our growing knowledge of important
      prognostic markers and emerging predictive biomarkers are needed. In this review
      we discuss new strategies to assess drug response in early phase clinical trial
      testing. 

PMID- 25046533
TI  - The blood-brain barrier: structure, function and therapeutic approaches to cross
      it.
AB  - The blood-brain barrier (BBB) is constituted by a specialized vascular
      endothelium that interacts directly with astrocytes, neurons and pericytes. It
      protects the brain from the molecules of the systemic circulation but it has to
      be overcome for the proper treatment of brain cancer, psychiatric disorders or
      neurodegenerative diseases, which are dramatically increasing as the population
      ages. In the present work we have revised the current knowledge on the cellular
      structure of the BBB and the different procedures utilized currently and those
      proposed to cross it. Chemical modifications of the drugs, such as increasing
      their lipophilicity, turn them more prone to be internalized in the brain. Other
      mechanisms are the use of molecular tools to bind the drugs such as small
      immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses
      favoring the drug delivery in brain. This fusion of the classical pharmacology
      with nanotechnology has opened a wide field to many different approaches with
      promising results to hypothesize that BBB will not be a major problem for the new
      generation of neuroactive drugs. The present review provides an overview of all
      state-of-the-art of the BBB structure and function, as well as of the classic
      strategies and these appeared in recent years to deliver drugs into the brain for
      the treatment of Central Nervous System (CNS) diseases.

PMID- 25046535
TI  - In vitro toxicity in long-term cell culture of MR contrast agents targeted to
      cartilage evaluation.
AB  - OBJECTIVE: Contrast-enhanced magnetic resonance (MR) imaging methods have been
      proposed for non-invasive evaluation of osteoarthritis (OA). We measured cell
      toxicities of cartilage-targeted low-generation dendrimer-linked nitroxide MR
      contrast agents and gadopentetate dimeglumine (Gd-DTPA) on cultured chondrocytes.
      DESIGN: A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was
      exposed for 48-h to different salts (citrate, maleate, tartrate) and
      concentrations of generation one or two diaminobutyl-linked nitroxides (DAB4-DLN
      or DAB8-DLN), Gd-DTPA, or staurosporine (positive control). Impact on microscopic
      cell appearance, MTT spectrophotometric assays of metabolic activity, and
      quantitative PicoGreen assays of DNA content (cell proliferation) were measured
      and compared to untreated cultures. RESULTS: Chondrocyte cultures treated with up
      to 7.5 mM Gd-DTPA for 48-h had no statistical differences in DNA content or MTT
      reaction compared to untreated cultures. At all doses, DAB4-DLN citrate treated
      cultures had results similar to untreated and Gd-DTPA-treated cultures. At doses
      >1 mM, DAB4-DLN citrate treated cultures showed statistically greater DNA and MTT
      reaction than maleate and tartrate DAB4-DLN salts. Cultures exposed to 5 mM or
      7.5 mM DAB8-DLN citrate exhibited rounded cells, poor cell proliferation, and
      barely detectable MTT reaction. Treatment with 0.1 MUM staurosporine caused
      chondrocyte death. CONCLUSION: Long-term exposure, greater than clinically
      expected, to either DAB4-DLN citrate or Gd-DTPA had no detectable toxicity with
      results equivalent to untreated cultures. DAB4-DLN citrate was more biocompatible
      than either the maleate or tartrate salts. Cells exposed for 48-h to 5 mM or 7.5
      mM DAB8-DLN salts demonstrated significant cell toxicity. Further evaluation of
      DAB8-DLN with clinically appropriate exposure times is required to determine the
      maximum useful concentration.

PMID- 25046534
TI  - Estrogen via estrogen receptor beta partially inhibits mandibular condylar
      cartilage growth.
AB  - OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women,
      suggesting a role for female hormones in the disease process. However, little is
      known about the role of estrogen receptor (ER) signaling in regulating mandibular
      condylar cartilage growth. Therefore, the goal of this study was to examine the
      effects of altered estrogen levels on the mandibular condylar cartilage in wild
      type (WT) and ER beta Knockout (KO) mice. MATERIALS AND METHODS: 21-day-old
      female WT (n = 37) and ER beta KO mice (n = 36) were either sham operated or
      ovariectomized, and treated with either placebo or estradiol. The mandibular
      condylar cartilage was evaluated by histomorphometry, proliferation was analyzed
      by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and
      assays on gene and protein expression of chondrocyte maturation markers were
      performed. RESULTS: In WT mice, ovariectomy caused a significant increase in
      mandibular condylar cartilage cell numbers, a significant increase in Sox9
      expression and a significant increase in proliferation compared with sham
      operated WT mice. In contrast, ovariectomy did not cause any of these effects in
      the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice
      caused a significant decrease in ER alpha expression and a significant increase
      in Sost expression compared with ovariectomized mice treated with placebo.
      Estrogen replacement treatment in ovariectomized ER beta KO mice caused a
      significant increase in Col2 expression, no change in ER alpha expression, and a
      significant increase in Sost expression. CONCLUSION: Estrogen via ER beta
      inhibits proliferation and ER alpha expression while estrogen independent of ER
      beta induces Col2 and Sost expression.

PMID- 25046536
TI  - Two-year clinical evaluation of chlorhexidine incorporation in two-step self-etch
      adhesive.
AB  - OBJECTIVES: The aim of this 24-month double-blind randomized paired-tooth
      clinical study was to evaluate the 2-year clinical performance of two self-etch
      adhesives containing or not chlorhexidine digluconate (CHX) in non-carious
      cervical lesions (NCCLs). METHODS: Twenty-two patients, with at least four NCCLs,
      participated in this study. After sample size calculation, 126 restorations were
      assigned to one of the following groups: CSE--Clearfil SE Bond (Kuraray); CSE/CHX
      -Clearfil SE Bond+CHX; ADS--AdheSE (Ivoclar Vivadent); and ADS/CHX--AdheSE+CHX.
      The composite resin Filtek Z-250 composite (3M ESPE) was placed incrementally by
      one expert operator. The restorations were evaluated at baseline and after 2
      years using the modified USPHS criteria. Statistical analyses were performed with
      Friedman repeated measures ANOVA by rank and Fisher exact test for significance
      in each pair (alpha=0.05). RESULTS: No significant difference was observed
      between baseline and 2-year for any criteria when adhesives with and without the
      addition of CHX were compared (p>0.05). ADS and ADS/CHX resulted in lower
      retention rates (82% on average) than CSE and CSE/CHX (97%) (p=0.02).
      CONCLUSIONS: The inclusion of CHX into the primer of both self-etch systems did
      not add clinical advantages over the 2-year period. Clearfil SE Bond resulted in
      better retention rate than AdheSE. CLINICAL SIGNIFICANCE: It is more important to
      choose a gold standard self-etch adhesive, like a Clearfil SE Bond, than to
      consider the inclusion of CHX in the self-etch adhesives.

PMID- 25046537
TI  - Developing neuroimaging phenotypes of the default mode network in PTSD:
      integrating the resting state, working memory, and structural connectivity.
AB  - Complementary structural and functional neuroimaging techniques used to examine
      the Default Mode Network (DMN) could potentially improve assessments of
      psychiatric illness severity and provide added validity to the clinical
      diagnostic process. Recent neuroimaging research suggests that DMN processes may
      be disrupted in a number of stress-related psychiatric illnesses, such as
      posttraumatic stress disorder (PTSD). Although specific DMN functions remain
      under investigation, it is generally thought to be involved in introspection and
      self-processing. In healthy individuals it exhibits greatest activity during
      periods of rest, with less activity, observed as deactivation, during cognitive
      tasks, e.g., working memory. This network consists of the medial prefrontal
      cortex, posterior cingulate cortex/precuneus, lateral parietal cortices and
      medial temporal regions. Multiple functional and structural imaging approaches
      have been developed to study the DMN. These have unprecedented potential to
      further the understanding of the function and dysfunction of this network.
      Functional approaches, such as the evaluation of resting state connectivity and
      task-induced deactivation, have excellent potential to identify targeted
      neurocognitive and neuroaffective (functional) diagnostic markers and may
      indicate illness severity and prognosis with increased accuracy or specificity.
      Structural approaches, such as evaluation of morphometry and connectivity, may
      provide unique markers of etiology and long-term outcomes. Combined, functional
      and structural methods provide strong multimodal, complementary and synergistic
      approaches to develop valid DMN-based imaging phenotypes in stress-related
      psychiatric conditions. This protocol aims to integrate these methods to
      investigate DMN structure and function in PTSD, relating findings to illness
      severity and relevant clinical factors. 

PMID- 25046538
TI  - Overexpression of GTP cyclohydrolase 1 feedback regulatory protein is protective
      in a murine model of septic shock.
AB  - Overproduction of nitric oxide (NO) by inducible NO synthase contributes toward
      refractory hypotension, impaired microvascular perfusion, and end-organ damage in
      septic shock patients. Tetrahydrobiopterin (BH4) is an essential NOS cofactor.
      GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for BH4 biosynthesis.
      Under inflammatory conditions, GCH1 activity and hence BH4 levels are increased,
      supporting pathological NOS activity. GCH1 activity can be controlled through
      allosteric interactions with GCH1 feedback regulatory protein (GFRP). We
      investigated whether overexpression of GFRP can regulate BH4 and NO production
      and attenuate cardiovascular dysfunction in sepsis. Sepsis was induced in mice
      conditionally overexpressing GFRP and wild-type littermates by cecal ligation and
      puncture. Blood pressure was monitored by radiotelemetry, and mesenteric blood
      flow was quantified by laser speckle contrast imaging. Blood biochemistry data
      were obtained using an iSTAT analyzer, and BH4 levels were measured in plasma and
      tissues by high-performance liquid chromatography. Increased BH4 and NO
      production and hypotension were observed in all mice, but the extents of these
      pathophysiological changes were attenuated in GFRP OE mice. Perturbations in
      blood biochemistry were similarly attenuated in GFRP OE compared with wild-type
      controls. These results suggest that GFRP overexpression regulates GCH1 activity
      during septic shock, which in turn limits BH4 bioavailability for iNOS. We
      conclude that the GCH1-GFRP axis is a critical regulator of BH4 and NO production
      and the cardiovascular derangements that occur in septic shock. 

PMID- 25046539
TI  - Isoproternenol increases vascular volume expansion and urinary output after a
      large crystalloid bolus in healthy volunteers.
AB  - BACKGROUND: The primary goal of fluid therapy is to maintain fluid homeostasis.
      Commonly used isotonic crystalloids are only marginally effective and contribute
      to fluid excess syndrome. In patients with decreased cardiovascular reserve,
      fluid therapy alone is not sufficient to maintain end-organ perfusion. Therefore,
      inotropes or vasoactive drugs are used to supplement fluid infusion. Recent
      animal data suggest that coinfusion of adrenergic agents modulate the
      distribution of fluid between the vascular and extravascular/interstitial
      compartments after a fluid bolus. We sought to determine if this effect would
      translate in humans by coadministering a beta-adrenergic agonist with fluid.
      METHODS: Nine healthy volunteers (aged 21-50 years) were randomly paired and
      received either a continuous isoproterenol infusion (ISO: 0.05 MUg/kg per minute)
      or 0.9% saline (control [CON]) 30min prior to a 25 mL/kg 0.9% NaCl fluid bolus.
      Hemodynamics, ventricular volume and function, and microcirculatory determinants
      (capillary filtration coefficient and oncotic pressure) were measured. Vascular
      and extravascular volume and fluid balance were determined. RESULTS: Compared
      with CON, ISO significantly increased heart rate (CON: 64.2 +/- 4.1 beats/min vs.
      ISO: 97.4 +/- 5.7 beats/min) and cardiac output (CON: 4.4 +/- 0.7 L/min vs. ISO:
      10.2 +/- 0.9) before fluid bolus. Isoproterenol significantly increased urinary
      output (ISO: 10.86 +/- 1.95 vs. control: 6.53 +/- 1.45 mL/kg) and reduced
      extravascular volume (7.98 +/- 2.0 vs. 14.15 +/- 1.1mL/kg). Isoproterenol
      prevented an increase in capillary filtration coefficient (1.74 +/- 0.4 vs. 3.21
      +/- 0.4 mL/min per mmHg . 10). CONCLUSIONS: Isoproterenol, a nonselective beta
      adrenergic agonist, augments vascular volume expansion and eliminates
      extravascular volume via enhanced diuresis, which may in part be due to enhanced
      endothelial barrier function.

PMID- 25046540
TI  - Induced hypothermia during resuscitation from hemorrhagic shock attenuates
      microvascular inflammation in the rat mesenteric microcirculation.
AB  - Microvascular inflammation occurs during resuscitation following hemorrhagic
      shock, causing multiple organ dysfunction and mortality. Preclinical evidence
      suggests that hypothermia may have some benefit in selected patients by
      decreasing this inflammation, but this effect has not been extensively studied.
      Intravital microscopy was used to visualize mesenteric venules of anesthetized
      rats in real time to evaluate leukocyte adherence and mast cell degranulation.
      Animals were randomly allocated to normotensive or hypotensive groups and further
      subdivided into hypothermic and normothermic resuscitation (n = 6 per group).
      Animals in the shock groups underwent mean arterial blood pressure reduction to
      40 to 45 mmHg for 1 h via blood withdrawal. During the first 2 h following
      resuscitation by infusion of shed blood plus double that volume of normal saline,
      rectal temperature of the hypothermic groups was maintained at 32 degrees C to 34
      degrees C, whereas the normothermic groups were maintained between 36 degrees C
      to 38 degrees C. The hypothermic group was then rewarmed for the final 2 h of
      resuscitation. Leukocyte adherence was significantly lower after 2 h of
      hypothermic resuscitation compared with normothermic resuscitation: (2.8 +/- 0.8
      vs. 8.3 +/- 1.3 adherent leukocytes, P = 0.004). Following rewarming, leukocyte
      adherence remained significantly different between hypothermic and normothermic
      shock groups: (4.7 +/- 1.2 vs. 9.5 +/- 1.6 adherent leukocytes, P = 0.038). Mast
      cell degranulation index (MDI) was significantly decreased in the hypothermic
      (1.02 +/- 0.04 MDI) versus normothermic (1.22 +/- 0.07 MDI) shock groups (P =
      0.038) after the experiment. Induced hypothermia during resuscitation following
      hemorrhagic shock attenuates microvascular inflammation in rat mesentery.
      Furthermore, this decrease in inflammation is carried over after rewarming takes
      place. 

PMID- 25046541
TI  - Farnesyltransferase inhibitor, tipifarnib, prevents
      galactosamine/lipopolysaccharide-induced acute liver failure.
AB  - Acute liver failure (ALF) is a fatal syndrome associated with massive hepatocyte
      death. There is no cure for ALF except liver transplantation. Protein
      farnesylation is a lipid modification of cysteine residues that is catalyzed by
      farnesyltransferase (FTase) and has been proposed as an integral component of
      acute inflammation. Previously, we have demonstrated that FTase inhibitors
      improve survival in mouse models of endotoxemia and sepsis. Here we studied the
      effects of FTase inhibitor, tipifarnib, on galactosamine
      (GalN)/lipopolysaccharide (LPS)-induced ALF. The effects of tipifarnib (10 mg/kg,
      i.p.) were studied in GalN (400 mg/kg, i.p.)- and LPS (3 MUg/kg)-challenged mice
      by histological and biochemical analyses. Galactosamine/LPS administration caused
      prominent liver injury characterized by the increased plasma alanine
      aminotransferase and aspartic aminotransferase levels, leading to significant
      mortality in mice. Tipifarnib inhibited GalN/LPS-induced caspase 3 activation,
      inflammatory cytokine production, and c-Jun N-terminal kinase phosphorylation in
      the liver. On the other hand, tipifarnib upregulated antiapoptotic protein, Bcl
      xL, in the liver after GalN/LPS challenge. Tipifarnib also protected primary
      hepatocytes from GalN/tumor necrosis factor alpha-induced cell death by
      inhibiting caspase 3 activation and upregulating antiapoptotic proteins.
      Galactosamine/LPS-induced liver injury was associated with increased protein
      farnesylation in the liver. Tipifarnib prevented protein farnesylation in the
      liver and markedly attenuated liver injury and mortality in GalN/LPS-challenged
      mice. These results suggest that protein farnesylation is a novel potential
      molecular target to prevent hepatocyte death and acute inflammatory liver failure
      in fulminant hepatitis. 

PMID- 25046542
TI  - Complete sequence of pABTJ2, a plasmid from Acinetobacter baumannii MDR-TJ,
      carrying many phage-like elements.
AB  - Acinetobacter baumannii is an important opportunistic pathogen in hospital, and
      the multidrug-resistant isolates of A. baumannii have been increasingly reported
      in recent years. A number of different mechanisms of resistance have been
      reported, some of which are associated with plasmid-mediated acquisition of
      genes. Therefore, studies on plasmids in A. baumannii have been a hot issue
      lately. We have performed complete genome sequencing of A. baumannii MDR-TJ,
      which is a multidrug-resistant isolate. Finalizing the remaining large scaffold
      of the previous assembly, we found a new plasmid pABTJ2, which carries many phage
      like elements. The plasmid pABTJ2 is a circular double-stranded DNA molecule,
      which is 110,967bp in length. We annotated 125 CDSs from pABTJ2 using IMG ER and
      ZCURVE_V, accounting for 88.28% of the whole plasmid sequence. Many phage-like
      elements and a tRNA-coding gene were detected in pABTJ2, which is rarely reported
      among A. baumannii. The tRNA gene is specific for asparagine codon GTT, which may
      be a small chromosomal sequence picked up through incorrect excision during
      plasmid formation. The phage-like elements may have been acquired during the
      integration process, as the GC content of the region carrying phage-like elements
      was higher than that of the adjacent regions. The finding of phage-like elements
      and tRNA-coding gene in pABTJ2 may provide a novel insight into the study of A.
      baumannii pan-plasmidome. 

PMID- 25046543
TI  - Attitudes of pregnant women towards personally controlled electronic, hospital
      held, and patient-held medical record systems: a survey study.
AB  - BACKGROUND: On July 1, 2012 the Australian Government launched the personally
      controlled electronic health record (PCEHR). This article surveys obstetric
      patients about their medical record preferences and identifies barriers to
      adoption of the PCEHR. MATERIALS AND METHODS: A survey study was conducted of
      antenatal patients attending a large Australian metropolitan hospital.
      Consecutive patients completed questionnaires during the launch phase of the
      PCEHR system. Quantitative and qualitative data were collected on demographics,
      computer access and familiarity, preference for medical record system, and
      perceived benefits and concerns. RESULTS: Of 528 women eligible to participate,
      474 completed the survey (89.8%). Respondents had high levels of home access to a
      computer (90.5%) and the Internet (87.1%) and were familiar with using computers
      in daily life (median Likert scale of 9 out of 10). Despite this, respondents
      preferred hospital-held paper records, and only one-third preferred a PCEHR; the
      remainder preferred patient-held records. Compared with hospital-held paper
      records, respondents felt a PCEHR would reduce the risk of lost records
      (p<0.0001) and improve staff communication (p<0.0001). However, there were
      significant concerns about confidentiality and privacy of the PCEHR (p<0.0001)
      and lack of control (p<0.0001). CONCLUSIONS: Consumers see advantages and
      disadvantages with the PCEHR, although the majority still prefer existing record
      systems. To increase uptake, confidentiality, privacy, and control concerns need
      to be addressed.

PMID- 25046544
TI  - Time-dependent effects of neuromuscular electrical stimulation on changes in
      spinal excitability are dependent on stimulation frequency: a preliminary study
      in healthy adults.
AB  - Neuromuscular electrical stimulation (NMES) can be used as treatment for
      spasticity. The present study examined differences in time-dependent effects of
      NMES depending on stimulation frequency. Forty healthy subjects were separated
      into four groups (no-stim, NMES of 50, 100, and 200 Hz). The un-conditioned H
      reflex amplitude and the H-reflex conditioning-test paradigm were used to measure
      the effectiveness on monosynaptic Ia excitation of motoneurons in the soleus
      (SOL) muscle, disynaptic reciprocal Ia inhibition from tibialis anterior (TA) to
      SOL, and presynaptic inhibition of SOL Ia afferents. Each trial consisted of a 30
      min period of NMES applied to the deep peroneal nerve followed by a 30-min period
      with no stimulation to measure prolonged effects. Measurements were performed
      periodically. Stimulation applied at all frequencies produced a significant
      reduction in monosynaptic Ia excitation of motoneurons in the SOL muscle,
      however, only stimulation with 50 Hz showed prolonged reduction after NMES. NMES
      frequency did not affect the amount of disynaptic reciprocal Ia inhibition and
      presynaptic inhibition of Ia afferents. The results show a frequency-dependent
      effect of NMES on the monosynaptic Ia excitation of motoneurons. This result has
      implications for selecting the optimal NMES frequency for treatment in patients
      with spasticity.

PMID- 25046545
TI  - Diesel and silica monitoring at two sites following hurricane sandy.
AB  - Following Hurricane Sandy, which hit New York City and New Jersey in October
      2012, industrial hygienists from the Mount Sinai and Belleview/New York
      University occupational medicine clinics conducted monitoring for diesel exhaust
      and silica in lower Manhattan and Rockaway Peninsula. Average daytime elemental
      carbon levels at three stations in lower Manhattan on December 4, 2012, ranged
      from 9 to18 MUg/m(3). Sub-micron particle counts at various times on the same day
      were over 200,000 particles per cubic centimeter on many streets in lower
      Manhattan. In Rockaway Peninsula on December 12, 2012, all average daytime
      elemental carbon levels were below a detection limit of approximately 7 MUg/m(3).
      The average daytime crystalline silica dust concentration was below detection at
      two sites on Rockaway Peninsula, and was 0.015 mg/m(3) quartz where sand was
      being replaced on the beach. The daily average levels of elemental carbon and
      airborne particulates that we measured are in the range of levels that have been
      found to cause respiratory effects in sensitive subpopulations like asthmatic
      patients after 2 hr of exposure. Control of exposure to diesel exhaust must be
      considered following natural disasters where diesel-powered equipment is used in
      cleanup and recovery. Although peak silica exposures were not likely captured in
      this study, but were reported by a government agency to have exceeded recommended
      guidelines for at least one cleanup worker, we recommend further study of silica
      exposures when debris removal operations or traffic create visible levels of
      suspended dust from soil or sand. 

PMID- 25046547
TI  - Effects of calcitriol on bone mineral density in patients treated with
      esomeprazole.
AB  - CONTEXT: Proton pump inhibitor (PPI) increases the risk of decrease in bone
      mineral density (BMD). However, whether calcitrol improves this situation is
      unknown. OBJECTIVE: The current study investigates the effects of calcitriol on
      BMD in patients with esomeprazole therapy. MATERIALS AND METHODS: Three hundred
      and eighty-six participants with gastrointestinal ulcerations were enrolled and
      randomly assigned into controlled and supplemented groups. Participants in the
      controlled group were prescribed esomeprazole (20 mg/qd), while the supplemented
      group was prescribed esomeprazole (20 mg/qd) and calcitriol (2.5 MUg/qd). BMD,
      serum levels of calcium, carboxy-terminal collagen crosslinks (CTX), and alkaline
      phosphatase (ALP) were assessed. RESULTS: (1) No significant between-group
      difference of age, gender, smoking, previous glucocorticoid use and hemoglobin
      level was found; (2) after 10.6 +/- 0.8 d of PPI therapy, BMD T score in the
      controlled group was slightly increased compared with initial (-1.25 +/- 0.08
      versus -1.28 +/- 0.06, p = 0.084), while there was no change in the supplemented
      group (-1.25 +/- 0.05 versus -1.26 +/- 0.03, p = 0.308); (3) during study
      termination, calcium level in the supplemented group was slightly higher than the
      controlled group (2.05 +/- 0.03 mmol/L versus 2.01 +/- 0.05 mmol/L, p = 0.073),
      while no significant differences of CTX (366.57 +/- 43.71 pg/mL versus 373.15 +/-
      50.23 pg/mL, p = 0.036) and ALP were found among these two groups (50.47 +/- 9.32
      U/L versus 52.23 +/- 10.45 U/L, p = 0.075). CONCLUSION: Patients with
      gastrointestinal ulcerations with esomeprazole therapy, calcitriol supplement
      showed no efficacy on BMD changes.

PMID- 25046548
TI  - Instructive nanofibrous scaffold comprising runt-related transcription factor 2
      gene delivery for bone tissue engineering.
AB  - Inducer molecules capable of regulating mesenchymal stem cell differentiation
      into specific lineages have proven effective in basic science and in preclinical
      studies. Runt-related transcription factor 2 (RUNX2) is considered to be the
      central gene involved in the osteoblast phenotype induction, which may be
      advantageous for inducing bone tissue regeneration. This work envisions the
      development of a platform for gene delivery, combining liposomes as gene delivery
      devices, with electrospun nanofiber mesh (NFM) as a tissue engineering scaffold.
      pDNA-loaded liposomes were immobilized at the surface of functionalized
      polycaprolactone (PCL) NFM. Human bone-marrow-derived mesenchymal stem cells
      (hBMSCs) cultured on RUNX2-loaded liposomes immobilized at the surface of
      electrospun PCL NFM showed enhanced levels of metabolic activity and total
      protein synthesis. RUNX2-loaded liposomes immobilized at the surface of
      electrospun PCL NFMs induce a long-term gene expression of eGFP and RUNX2 by
      cultured hBMSCs. Furthermore, osteogenic differentiation of hBMSCs was also
      achieved by the overexpression of other osteogenic markers in medium free of
      osteogenic supplementation. These findings demonstrate that surface
      immobilization of RUNX2 plasmid onto elestrospun PCL NFM can produce long-term
      gene expression in vitro, which may be employed to enhance the osteoinductive
      properties of scaffolds used for bone tissue engineering strategies.

PMID- 25046549
TI  - A conspicuous clay ovoid in Nakhla: evidence for subsurface hydrothermal
      alteration on Mars with implications for astrobiology.
AB  - Abstract A conspicuous biomorphic ovoid structure has been discovered in the
      Nakhla martian meteorite, made of nanocrystalline iron-rich saponitic clay and
      amorphous material. The ovoid is indigenous to Nakhla and occurs within a late
      formed amorphous mesostasis region of rhyolitic composition that is interstitial
      to two clinopyroxene grains with Al-rich rims, and contains acicular apatite
      crystals, olivine, sulfides, Ti-rich magnetite, and a new mineral of the rhoenite
      group. To infer the origin of the ovoid, a large set of analytical tools was
      employed, including scanning electron microscopy and backscattered electron
      imaging, wavelength-dispersive X-ray analysis, X-ray mapping, Raman spectroscopy,
      time-of-flight secondary ion mass spectrometry analysis, high-resolution
      transmission electron microscope imaging, and atomic force microscope topographic
      mapping. The concentric wall of the ovoid surrounds an originally hollow volume
      and exhibits internal layering of contrasting nanotextures but uniform chemical
      composition, and likely inherited its overall shape from a preexisting vesicle in
      the mesostasis glass. A final fibrous layer of Fe-rich phases blankets the
      interior surfaces of the ovoid wall structure. There is evidence that the parent
      rock of Nakhla has undergone a shock event from a nearby bolide impact that
      melted the rims of pyroxene and the interstitial matter and initiated an igneous
      hydrothermal system of rapidly cooling fluids, which were progressively mixed
      with fluids from the melted permafrost. Sharp temperature gradients were
      responsible for the crystallization of Al-rich clinopyroxene rims, rhoenite,
      acicular apatites, and the quenching of the mesostasis glass and the vesicle.
      During the formation of the ovoid structure, episodic fluid infiltration events
      resulted in the precipitation of saponite rinds around the vesicle walls, altered
      pyrrhotite to marcasite, and then isolated the ovoid wall structure from the rest
      of the system by depositing a layer of iron oxides/hydroxides. Carbonates,
      halite, and sulfates were deposited last within interstitial spaces and along
      fractures. Among three plausible competing hypotheses here, this particular
      abiotic scenario is considered to be the most reasonable explanation for the
      formation of the ovoid structure in Nakhla, and although compelling evidence for
      a biotic origin is lacking, it is evident that the martian subsurface contains
      niche environments where life could develop.

PMID- 25046550
TI  - Ipilimumab for advanced melanoma: experience from the Spanish Expanded Access
      Program.
AB  - Ipilimumab, a fully human, recombinant, monoclonal antibody to cytotoxic T
      lymphocyte antigen 4 improves overall survival (OS) in previously treated and
      untreated metastatic melanoma. This retrospective analysis reports data gathered
      by a questionnaire on the demographics, outcomes, and toxicity of ipilimumab
      administered through an Expanded Access Program (EAP). Ipilimumab 3 mg/kg was
      administered intravenously every 3 weeks for four cycles to adults with
      metastatic melanoma. Efficacy outcomes included complete response, partial
      response (PR), progressive disease, stabilized disease, and OS. EAP data were
      collected from EAP physicians. A subgroup analysis examined efficacy in elderly
      patients (>=70 years) and factors predictive of survival were identified. Of 355
      requests for ipilimumab, resulting in 288 treatments, completed questionnaires
      were received for 153 ipilimumab recipients (median age 58 years, 57.2% men).
      Efficacy was evaluated in 144 patients: complete response in 1.3%, PR in 9.6%, PR
      with previous progression 8.4%, stabilized disease in 14.5%, and progressive
      disease in 66.2%. The median OS was 6.5 months (199 days); 1-year survival was
      32.9%. Predictive survival factors included lymphocytes over 1000/ml (P=0.0008)
      and lactate dehydrogenase more than 1.5*upper limit of normal (P=0.003).
      Cutaneous, hepatic, and gastrointestinal toxicities were mild. In 30 patients
      aged more than 70 years, ipilimumab efficacy and tolerability was similar to that
      of the overall population. In the clinical practice setting, ipilimumab is
      effective and well tolerated in patients with advanced melanoma, including
      elderly patients, when administered at the recommended dosage. Ipilimumab
      improves treatment options for patients who, until recently, have had little hope
      of an improved prognosis. 

PMID- 25046551
TI  - Outcomes for high-energy distal femur articular fractures.
AB  - BACKGROUND: Distal femur fractures are relatively rare injuries that usually
      require surgical treatment. Angular-stable plates allowing for anatomical
      repositioning and stable fixation of splinters, particularly in articular
      fractures, are commonly used in such cases. The goal of the study was to analyze
      the outcomes of the surgical treatment of high-energy articular fractures of
      distal femur. MATERIAL AND METHODS: The study included 22 patients treated in
      years 2007-2013. The average follow-up period was 39.5 months. The range of knee
      motion was recorded during follow-up visits. Treatment outcomes are presented
      using the Prichett's criteria as well as using IKDC and KOOS scores. Bone union
      and lower limb axial deformity were assessed using X-ray images. RESULTS: The
      average range of motion was 0-99 degrees. According to Prichett's criteria, a
      total of 54% good and very good results as well as 36% of satisfactory results
      were recorded. The average IKDC score was 59.4 points while the average KOOS
      score was 54.7 points Bone union was achieved in 91.6% of fractures. Axial
      deformity was rare, and correlation between the valgus angle and the clinical and
      functional outcomes was observed. CONCLUSIONS: The applied methods for internal
      fixation afforded satisfactory treatment outcomes in most patients with high
      energy distal femur fractures. No significant reduction in the mobility of the
      affected knee or axial deformation are observed after proper repositioning of
      distal femur fracture splinters using an angular-stable plate.

PMID- 25046552
TI  - Movable shark scales act as a passive dynamic micro-roughness to control flow
      separation.
AB  - Shark scales on fast-swimming sharks have been shown to be movable to angles in
      excess of 50 degrees , and we hypothesize that this characteristic gives this
      shark skin a preferred flow direction. During the onset of separation, flow
      reversal is initiated close to the surface. However, the movable scales would be
      actuated by the reversed flow thereby causing a greater resistance to any further
      flow reversal and this mechanism would disrupt the process leading to eventual
      flow separation. Here we report for the first time experimental evidence of the
      separation control capability of real shark skin through water tunnel testing.
      Using skin samples from a shortfin mako Isurus oxyrinchus, we tested a pectoral
      fin and flank skin attached to a NACA 4412 hydrofoil and separation control was
      observed in the presence of movable shark scales under certain conditions in both
      cases. We hypothesize that the scales provide a passive, flow-actuated mechanism
      acting as a dynamic micro-roughness to control flow separation. 

PMID- 25046555
TI  - Trans-cis isomerization of vinylketones through triplet 1,2-biradicals.
AB  - The irradiation of trans-vinylketones 1a-c yields the corresponding cis isomers
      2a-c. Laser flash photolysis of 1a and 1b with 308 and 355 nm lasers results in
      their triplet ketones (T1K of 1), which rearrange to form triplet 1,2-biradicals
      3a and 3b, respectively, whereas irradiation with a 266 nm laser produces their
      cis-isomers through singlet reactivity. Time-resolved IR spectroscopy of 1a with
      266 nm irradiation confirmed that 2a is formed within the laser pulse. In
      comparison, laser flash photolysis of 1c with a 308 nm laser showed only the
      formation of 2c through singlet reactivity. At cryogenic temperatures, the
      irradiation of 1 also resulted in 2. DFT calculations were used to aid in the
      characterization of the excited states and biradicals involved in the cis-trans
      isomerization and to support the mechanism for the cis-trans isomerization on the
      triplet surface. 

PMID- 25046553
TI  - Vaccine-associated varicella and rubella infections in severe combined
      immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected
      by tandem whole exome sequencing and chromosomal microarray.
AB  - In areas without newborn screening for severe combined immunodeficiency (SCID),
      disease-defining infections may lead to diagnosis, and in some cases, may not be
      identified prior to the first year of life. We describe a female infant who
      presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired
      rubella infections at 13 months of age. Immunological evaluations demonstrated
      neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor
      lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody
      production to VZV infection and routine immunizations. A combination of whole
      exome sequencing and custom-designed chromosomal microarray with exon coverage of
      primary immunodeficiency genes detected compound heterozygous mutations (one
      single nucleotide variant and one intragenic copy number variant involving one
      exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected
      in pretransplant blood and buccal DNA and maternal engraftment (5-10%)
      demonstrated in pretransplant blood DNA. This may be responsible for the
      patient's unusual immunological phenotype compared to classical interleukin (IL)
      7Ralpha deficiency. Disseminated VZV was controlled with anti-viral and immune
      based therapy, and umbilical cord blood stem cell transplantation was successful.
      Retrospectively performed T cell receptor excision circle (TREC) analyses
      completed on neonatal Guthrie cards identified absent TREC. This case emphasizes
      the danger of live viral vaccination in severe combined immunodeficiency (SCID)
      patients and the importance of newborn screening to identify patients prior to
      high-risk exposures. It also illustrates the value of aggressive pathogen
      identification and treatment, the influence newborn screening can have on
      morbidity and mortality and the significant impact of newer genomic diagnostic
      tools in identifying the underlying genetic aetiology for SCID patients. 

PMID- 25046554
TI  - Integrative and personalized QSAR analysis in cancer by kernelized Bayesian
      matrix factorization.
AB  - With data from recent large-scale drug sensitivity measurement campaigns, it is
      now possible to build and test models predicting responses for more than one
      hundred anticancer drugs against several hundreds of human cancer cell lines.
      Traditional quantitative structure-activity relationship (QSAR) approaches focus
      on small molecules in searching for their structural properties predictive of the
      biological activity in a single cell line or a single tissue type. We extend this
      line of research in two directions: (1) an integrative QSAR approach predicting
      the responses to new drugs for a panel of multiple known cancer cell lines
      simultaneously and (2) a personalized QSAR approach predicting the responses to
      new drugs for new cancer cell lines. To solve the modeling task, we apply a novel
      kernelized Bayesian matrix factorization method. For maximum applicability and
      predictive performance, the method optionally utilizes genomic features of cell
      lines and target information on drugs in addition to chemical drug descriptors.
      In a case study with 116 anticancer drugs and 650 cell lines, we demonstrate the
      usefulness of the method in several relevant prediction scenarios, differing in
      the amount of available information, and analyze the importance of various types
      of drug features for the response prediction. Furthermore, after predicting the
      missing values of the data set, a complete global map of drug response is
      explored to assess treatment potential and treatment range of therapeutically
      interesting anticancer drugs. 

PMID- 25046556
TI  - Reagentless uric acid biosensor based on Ni microdiscs-loaded NiO thin film
      matrix.
AB  - The development of a noninvasive test for uric acid has been the holy grail of
      uric acid detection research over the last decade. In the present work, a novel
      matrix comprising of a NiO thin film (a biocompatible material) loaded with Ni
      microdiscs was prepared on an ITO-coated glass substrate (Ni/NiO/ITO) with the
      help of RF sputtering for the reagentless detection of uric acid. The
      bioelectrode was fabricated by immobilizing uricase using a physical adsorption
      technique on the surface of the Ni/NiO/ITO electrode. The prepared matrix was
      found to be efficient in sensing biological processes occurring on the surface of
      the bioelectrode (Ur/Ni/NiO/ITO) in the presence of the analyte (uric acid) to
      obtain an electronic output. The biosensor exhibits a high sensitivity (431.09
      MUA mM(-1)), low Km value (0.15 mM), high apparent enzyme activity (5.07 * 10(-2)
      units per cm(2)), high shelf life (20 weeks) and good selectivity for the
      detection of uric acid over a wide concentration range (0.05 mM to 1 mM) without
      any external mediator in the PBS buffer. The obtained results are encouraging for
      the realization of a reagentless uric acid biosensor with efficient sensing
      response characteristics. 

PMID- 25046557
TI  - Preventing corona effects: multiphosphonic acid poly(ethylene glycol) copolymers
      for stable stealth iron oxide nanoparticles.
AB  - When dispersed in biological fluids, engineered nanoparticles are selectively
      coated with proteins, resulting in the formation of a protein corona. It is
      suggested that the protein corona is critical in regulating the conditions of
      entry into the cytoplasm of living cells. Recent reports describe this phenomenon
      as ubiquitous and independent of the nature of the particle. For nanomedicine
      applications, however, there is a need to design advanced and cost-effective
      coatings that are resistant to protein adsorption and that increase the
      biodistribution in vivo. In this study, phosphonic acid poly(ethylene glycol)
      copolymers were synthesized and used to coat iron oxide particles. The copolymer
      composition was optimized to provide simple and scalable protocols as well as
      long-term stability in culture media. It is shown that polymers with multiple
      phosphonic acid functionalities and PEG chains outperform other types of coating,
      including ligands, polyelectrolytes, and carboxylic acid functionalized PEG.
      PEGylated particles exhibit moreover exceptional low cellular uptake, of the
      order of 100 femtograms of iron per cell. The present approach demonstrates that
      the surface chemistry of engineered particles is a key parameter in the
      interactions with cells. It also opens up new avenues for the efficient
      functionalization of inorganic surfaces. 

PMID- 25046558
TI  - Parallel-transmission-enabled three-dimensional T2 -weighted imaging of the human
      brain at 7 Tesla.
AB  - PURPOSE: A promise of ultra high field MRI is to produce images of the human
      brain with higher spatial resolution due to an increased signal to noise ratio.
      Yet, the shorter radiofrequency wavelength induces an inhomogeneous distribution
      of the transmit magnetic field and thus challenges the applicability of MRI
      sequences which rely on the spin excitation homogeneity. In this work, the
      ability of parallel-transmission to obtain high-quality T2 -weighted images of
      the human brain at 7 Tesla, using an original pulse design method is evaluated.
      METHODS: Excitation and refocusing square pulses of a SPACE sequence were
      replaced with short nonselective transmit-SENSE pulses individually tailored with
      the gradient ascent pulse engineering algorithm, adopting a kT -point trajectory
      to simultaneously mitigate B1 (+) and DeltaB0 nonuniformities. RESULTS: In vivo
      experiments showed that exploiting parallel-transmission at 7T with the proposed
      methodology produces high quality T2 -weighted whole brain images with uniform
      signal and contrast. Subsequent white and gray matter segmentation confirmed the
      expected improvements in image quality. CONCLUSION: This work demonstrates that
      the adopted formalism based on optimal control, combined with the kT -point
      method, successfully enables three-dimensional T2 -weighted brain imaging at 7T
      devoid of artifacts resulting from B1 (+) inhomogeneity.

PMID- 25046559
TI  - Whole exome sequencing for the identification of a new mutation in TGFB2 involved
      in a familial case of non-syndromic aortic disease.
AB  - BACKGROUND: Non-syndromic aortic disease (NSAD) is a frequently asymptomatic but
      potentially lethal disease characterised by familial cases of thoracic aortic
      aneurysms and dissections. This monogenic but genetically heterogeneous condition
      is primarily inherited as an autosomal dominant disorder with low penetrance and
      variable expression. Mutations in ACTA2, TGFBR1, TGFBR2, MYH11, SMAD3, MYLK, and
      FBN1 genes have been described but still, there are many unresolved familial
      cases. METHODS: The whole exome of two distantly related and affected members of
      a Spanish family with multiple cases of NSAD was analysed through 5500 SOLiD(TM)
      System for the identification of shared and putative pathogenic variants.
      RESULTS: A new mutation termed c.C1042T:p.R348C (NM_001135599.2) was identified
      in TGFB2, a gene located in an evolutionary highly conserved region (Chr1:
      218,519,577-218,617,961) that has been recently connected to this disease. The
      analysis of other family members using capillary sequencing confirmed
      cosegregation of the mutation with the disease and its incomplete penetrance.
      CONCLUSIONS: The repeated implication of TGFB2 in the development of thoracic
      aortic aneurysms and dissections suggests that this gene should be considered
      during genetic diagnosis of this disease. An accurate diagnosis of affected
      individuals and additional family members at risk allows for a personalised and
      more efficient gene-based follow-up and treatment. Finally, the reiterative
      presence of common musculoskeletal and craniofacial additional features in
      patients with TGFB2 mutations suggests the existence of a new yet undefined
      connective tissue syndrome responsible for not only aortic dilation, but also for
      the other extracardiac alterations present in the affected patients.

PMID- 25046560
TI  - Directed solid-phase synthesis of trisubstituted imidazo[4,5-c]pyridines and
      imidazo[4,5-b]pyridines.
AB  - An efficient method is described for the solid-supported synthesis of imidazo[4,5
      b]pyridines and imidazo[4,5-c]pyridines from 2,4-dichloro-3-nitropyridine. The
      key pyridine building block was reacted with polymer-supported amines, followed
      by replacement of the second chlorine with amines, nitro group reduction, and
      imidazole ring closure with aldehydes. Depending on the combination of polymer
      supported and solution-phase reagents, the strategy allowed for the simple
      preparation of the target trisubstituted derivatives with variable positioning of
      the pyridine nitrogen atom. Additionally, after a slight modification of the
      method, the preparation of strictly isomeric imidazopyridines was possible. 

PMID- 25046561
TI  - The impact of preoperative testing for blood glucose concentration and
      haemoglobin A1c on mortality, changes in management and complications in
      noncardiac elective surgery: a systematic review.
AB  - BACKGROUND: The risks associated with surgery are elevated in patients with
      diabetes mellitus. For this reason, preoperative diagnostics frequently include
      the measurement of blood glucose and haemoglobin A1c (HbA1c), but it is unclear
      whether these tests contribute to improved perioperative or postoperative
      outcomes. OBJECTIVES: This systematic review aimed to evaluate the evidence that
      preoperative testing for blood glucose and HbA1c might influence the following
      outcome parameters: changes in clinical management; mortality; and the incidence
      of perioperative and postoperative complications in patients undergoing elective,
      noncardiac surgery. DESIGN: We performed a systematic search of the literature
      from January 2001 to March 2013, thus updating a review carried out by the
      National Institute for Health and Clinical Excellence (NICE) up to the year 2001.
      ELIGIBILITY CRITERIA: Controlled studies including cohort and case-control
      studies with a population of at least 60 patients were eligible. RESULTS: The
      search retrieved 1346 records (including hand-search). Twenty-two studies met all
      inclusion criteria and were included in the review. Fifteen cohort and two case
      control studies evaluated the effectiveness of preoperative blood glucose testing
      and nine studies the effectiveness of testing HbA1c. Four of the included studies
      evaluated both tests. There were no data derived from high-quality studies
      supporting routine preoperative testing for blood glucose or HbA1c in otherwise
      healthy adult patients undergoing elective noncardiac surgery. Only in vascular
      and orthopaedic surgery may screening identify patients at an increased risk.
      CONCLUSION: Preoperative blood glucose testing and testing for HbA1c is not
      required in nondiabetic patients unless there are clinical sings arousing
      suspicion. Patients scheduled for vascular and orthopaedic surgery carry an
      elevated risk justifying preoperative testing for blood glucose or HbA1c as a
      screening tool.

PMID- 25046562
TI  - Ultrasonographic findings in 38 horses with septic arthritis/tenosynovitis.
AB  - Septic arthritis/tenosynovitis in the horse can have life-threatening
      consequences. The purpose of this cross-sectional retrospective study was to
      describe ultrasound characteristics of septic arthritis/tenosynovitis in a group
      of horses. Diagnosis of septic arthritis/tenosynovitis was based on historical
      and clinical findings as well as the results of the synovial fluid analysis
      and/or positive synovial culture. Ultrasonographic findings recorded were degree
      of joint/sheath effusion, degree of synovial membrane thickening, echogenicity of
      the synovial fluid, and presence of hyperechogenic spots and fibrinous
      loculations. Ultrasonographic findings were tested for dependence on the cause of
      sepsis, time between admission and beginning of clinical signs, and the white
      blood cell counts in the synovial fluid. Thirty-eight horses with confirmed
      septic arthritis/tenosynovitis of 43 joints/sheaths were included. Degree of
      effusion was marked in 81.4% of cases, mild in 16.3%, and absent in 2.3%.
      Synovial thickening was mild in 30.9% of cases and moderate/severe in 69.1%.
      Synovial fluid was anechogenic in 45.2% of cases and echogenic in 54.8%.
      Hyperechogenic spots were identified in 32.5% of structures and fibrinous
      loculations in 64.3%. Relationships between the degree of synovial effusion,
      degree of the synovial thickening, presence of fibrinous loculations, and the
      time between admission and beginning of clinical signs were identified, as well
      as between the presence of fibrinous loculations and the cause of sepsis (P <=
      0.05). Findings indicated that ultrasonographic findings of septic
      arthritis/tenosynovitis may vary in horses, and may be influenced by time between
      admission and beginning of clinical signs. 

PMID- 25046564
TI  - Probing water environment of Trp59 in ribonuclease T1: insight of the structure
      water network relationship.
AB  - In this study, we used the tryptophan analogue, (2,7-aza)Trp, which exhibits
      water catalyzed proton transfer isomerization among N(1)-H, N(7)-H, and N(2)-H
      isomers, to probe the water environment of tryptophan-59 (Trp59) near the
      connecting loop region of ribonuclease Tl (RNase T1) by replacing the tryptophan
      with (2,7-aza)Trp. The resulting (2,7-aza)Trp59 triple emission bands and their
      associated relaxation dynamics, together with relevant data of 7-azatryptophan
      and molecular dynamics (MD) simulation, lead us to propose two Trp59 containing
      conformers in RNase T1, namely, the loop-close and loop-open forms. Water is rich
      in the loop-open form around the proximity of (2,7-aza)Trp59, which catalyzes
      (2,7-aza)Trp59 proton transfer in the excited state, giving both N(1)-H and N(7)
      H isomer emissions. The existence of N(2)-H isomer in the loop-open form,
      supported by the MD simulation, is mainly due to the specific hydrogen bonding
      between N(2)-H proton and water molecule that bridges N(2)-H and the amide oxygen
      of Pro60, forming a strong network. The loop-close form is relatively tight in
      space, which squeezes water molecules out of the interface of alpha-helix and
      beta2 strand, joined by the connecting loop region; accordingly, the water-scant
      environment leads to the sole existence of the N(1)-H isomer emission. MD
      simulation also points out that the Trp-water pairs appear to preferentially
      participate in a hydrogen bond network incorporating polar amino acid moieties on
      the protein surface and bulk waters, providing the structural dynamic features of
      the connecting loop region in RNase T1. 

PMID- 25046565
TI  - Emergent ion-gated binding of cationic host-guest complexes within cationic
      M12L24 molecular flasks.
AB  - "Molecular flasks" are well-defined supramolecular cages that can encapsulate one
      or more molecular guests within their cavities and, in so doing, change the
      physical properties and reactivities of the guests. Although molecular flasks are
      powerful tools for manipulating matter on the nanoscale, most of them are limited
      in their scope because of size restrictions. Recently, however, increasingly
      large and diverse supramolecular cages have become available with enough space in
      their cavities for larger chemical systems such as polymers, nanoparticles, and
      biomolecules. Here we report how a class of metallosupramolecular cages known as
      M12L24 polyhedra have been adapted to serve as nanometer-scale containers for
      solutions of a pseudorotaxane host-guest complex based on a tetracationic
      cyclophane host, cyclobis(paraquat-p-phenylene) (CBPQT(4+)), and a 1,5
      dioxynaphthalene (DNP) guest. Remarkably, the hierarchical integration of
      pseudorotaxanes and M12L24 superhosts causes the system to express stimulus
      responsive behavior, a property which can be described as emergent because
      neither the DNP?CBPQT(4+) nor the M12L24 assemblies exhibit this behavior
      independently. The DNP-containing M12L24 molecular flasks are effectively "sealed
      off" to CBPQT(4+) until ions are added as a stimulus to "open" them. The
      electrolyte stimulus reduces the electrostatic screening distance in solution,
      allowing favorable DNP?CBPQT(4+) host-guest interactions to overcome repulsive
      Coulombic interactions between the cationic M12L24 cages and CBPQT(4+) rings.
      This unusual example of ion-gated transport into chemical nanocontainers is
      reminiscent of transmembrane ion channels which act as gates to the cell, with
      the important difference that this system is reversible and operates at
      equilibrium. 

PMID- 25046566
TI  - Imaging cleared intact biological systems at a cellular level by 3DISCO.
AB  - Tissue clearing and subsequent imaging of transparent organs is a powerful method
      to analyze fluorescently labeled cells and molecules in 3D, in intact organs.
      Unlike traditional histological methods, where the tissue of interest is
      sectioned for fluorescent imaging, 3D imaging of cleared tissue allows
      examination of labeled cells and molecules in the entire specimen. To this end,
      optically opaque tissues should be rendered transparent by matching the
      refractory indices throughout the tissue. Subsequently, the tissue can be imaged
      at once using laser-scanning microscopes to obtain a complete high-resolution 3D
      image of the specimen. A growing list of tissue clearing protocols including
      3DISCO, CLARITY, Sca/e, ClearT2, and SeeDB provide new ways for researchers to
      image their tissue of interest as a whole. Among them, 3DISCO is a highly
      reproducible and straightforward method, which can clear different types of
      tissues and can be utilized with various microscopy techniques. This protocol
      describes this straightforward procedure and presents its various applications.
      It also discusses the limitations and possible difficulties and how to overcome
      them. 

PMID- 25046567
TI  - An Fc-optimized NKG2D-immunoglobulin G fusion protein for induction of natural
      killer cell reactivity against leukemia.
AB  - Recruitment of Fc-receptor-bearing effector cells, such as natural killer (NK)
      cells, is a feature critical for the therapeutic success of antitumor antibodies
      and can be improved by the modifications of an antibody's Fc part. The various
      ligands of the activating immunoreceptor NKG2D, NKG2DL) are selectively expressed
      on malignant cells including leukemia. We here took advantage of the tumor
      associated expression of NKG2DL for targeting leukemic cells by NKG2D
      immunoglobulin G (IgG)1 fusion proteins containing modified Fc parts. Compared to
      NKG2D-Fc containing a wild-type Fc part (NKG2D-Fc-WT), our mutants (S239D/I332E
      and E233P/L234V/L235A/DeltaG236/A327G/A330S) displayed highly enhanced (NKG2D-Fc
      ADCC) and abrogated (NKG2D-Fc-KO) affinity to the NK cell Fc receptor,
      respectively. Functional analyses with allogenic as well as autologous NK cells
      and primary malignant cells of leukemia patients revealed that NKG2D-Fc-KO
      significantly reduced NK reactivity by blocking immunostimulatory NKG2D-NKG2DL
      interaction. NKG2D-Fc-WT already enhanced antileukemia reactivity by inducing
      antibody-dependent cellular cytotoxicity (ADCC) with NKG2D-Fc-ADCC mediating
      significantly stronger effects. Parallel application of NKG2D-Fc-ADCC with
      Rituximab caused additive effects in lymphoid leukemia. In line with the tumor
      associated expression of NKG2DL, no NK cell ADCC against resting healthy blood
      cells was induced. Thus, NKG2D-Fc-ADCC potently enhances NK antileukemia
      reactivity despite the inevitable reduction of activating signals upon binding to
      NKG2DL and may constitute an attractive means for immunotherapy of leukemia. 

PMID- 25046569
TI  - The persistence of Salmonella following desiccation under feed processing
      environmental conditions: a subject of relevance.
AB  - Although Salmonella persistence has been predominantly linked to biofilm
      formation, the physiological state of Salmonella should also be considered as a
      possible pathway for persistence and survival in the feed industry. Hence, the
      purpose of this study was to assess the extent of viability of Salmonella cells
      through long-term desiccation periods under conditions typically found in feed
      processing environments, and whether these same cells could resuscitate and cause
      salmonellosis in vivo. We showed that upon desiccation, Salmonella Agona, a
      representative feed industry isolate and Salmonella Typhimurium ATCC 14028, a
      laboratory strain, were induced into a nonculturable state at 35 and 85% relative
      humidity conditions, at defined temperatures of 30 and 12 degrees C,
      respectively. Although the reduction in culturable cells was more than 6 log10 ,
      metabolic activity was found in more than 1% of the population. Desiccation
      induced nonculturable Salm. Typhimurium could not be revived and were nonvirulent
      in a mouse model following infection through oral gavage. These results suggest
      that the specific conditions for reviving nonculturable Salmonella after long
      periods of desiccation are yet to be fully identified. The need for mapping key
      factors involved in the persistence of Salmonella would help better detect it and
      improve feed safety measures. SIGNIFICANCE AND IMPACT OF THE STUDY: While
      Salmonella has been shown to persist for years in feed processing environments,
      it is still unknown how temperature and humidity affect the persistence of
      Salmonella cells over time in terms of their metabolic states and cultivability.
      Here, we show that long-term exposure to feed processing environmental conditions
      induces Salmonella into a nonculturable state even though about 1% of the
      population remains metabolically active. This has significant implications when
      monitoring Salmonella from the environment which could yield false-negative
      results using conventional pre-enrichment detection methods.

PMID- 25046568
TI  - Construction of vapor chambers used to expose mice to alcohol during the
      equivalent of all three trimesters of human development.
AB  - Exposure to alcohol during development can result in a constellation of
      morphological and behavioral abnormalities that are collectively known as Fetal
      Alcohol Spectrum Disorders (FASDs). At the most severe end of the spectrum is
      Fetal Alcohol Syndrome (FAS), characterized by growth retardation, craniofacial
      dysmorphology, and neurobehavioral deficits. Studies with animal models,
      including rodents, have elucidated many molecular and cellular mechanisms
      involved in the pathophysiology of FASDs. Ethanol administration to pregnant
      rodents has been used to model human exposure during the first and second
      trimesters of pregnancy. Third trimester ethanol consumption in humans has been
      modeled using neonatal rodents. However, few rodent studies have characterized
      the effect of ethanol exposure during the equivalent to all three trimesters of
      human pregnancy, a pattern of exposure that is common in pregnant women. Here, we
      show how to build vapor chambers from readily obtainable materials that can each
      accommodate up to six standard mouse cages. We describe a vapor chamber paradigm
      that can be used to model exposure to ethanol, with minimal handling, during all
      three trimesters. Our studies demonstrate that pregnant dams developed
      significant metabolic tolerance to ethanol. However, neonatal mice did not
      develop metabolic tolerance and the number of fetuses, fetus weight, placenta
      weight, number of pups/litter, number of dead pups/litter, and pup weight were
      not significantly affected by ethanol exposure. An important advantage of this
      paradigm is its applicability to studies with genetically-modified mice.
      Additionally, this paradigm minimizes handling of animals, a major confound in
      fetal alcohol research. 

PMID- 25046570
TI  - The transfusion dilemma: more, less, or more organized?

PMID- 25046571
TI  - Diaphragmatic electrical activity: a new tool to assess lung hyperinflation?

PMID- 25046572
TI  - qPCR is a sensitive and rapid method for detection of cytomegaloviral DNA in
      formalin-fixed, paraffin-embedded biopsy tissue.
AB  - It is crucial to identify cytomegalovirus (CMV) infection in the gastrointestinal
      (GI) tract of immunosuppressed patients, given their greater risk for developing
      severe infection. Many laboratory methods for the detection of CMV infection have
      been developed, including serology, viral culture, and molecular methods. Often,
      these methods reflect systemic involvement with CMV and do not specifically
      identify local tissue involvement. Therefore, detection of CMV infection in the
      GI tract is frequently done by traditional histology of biopsy tissue.
      Hematoxylin and eosin (H&E) staining in conjunction with immunohistochemistry
      (IHC) have remained the mainstays of examining these biopsies. H&E and IHC
      sometimes result in atypical (equivocal) staining patterns, making interpretation
      difficult. It was shown that quantitative polymerase chain reaction (qPCR) for
      CMV can successfully be performed on formalin-fixed, paraffin-embedded (FFPE)
      biopsy tissue for very high sensitivity and specificity. The goal of this
      protocol is to demonstrate how to perform qPCR testing for the detection of CMV
      in FFPE biopsy tissue in a clinical laboratory setting. This method is likely to
      be of great benefit for patients in cases of equivocal staining for CMV in GI
      biopsies. 

PMID- 25046573
TI  - Monte Carlo-quantum mechanics study of magnetic properties of hydrogen peroxide
      in liquid water.
AB  - A theoretical study of magnetic properties of hydrogen peroxide in water has been
      carried out by means of Monte Carlo simulation and quantum mechanics
      calculations. The solvent effects were evaluated in supermolecular structures
      generated by simulations in the NPT ensemble. The solute-solvent structure was
      analyzed in terms of radial distribution functions, and the solute-solvent
      hydrogen bonds were identified with geometric and energetic criteria.
      Approximately three water molecules are hydrogen bonded to H2O2 (0.6 and 0.8 in
      each hydrogen and oxygen atom, respectively, of the H2O2). Although, on average,
      both hydroxyls of the peroxide are equivalent, the distribution of hydrogen
      bonded water molecules is highly asymmetric. Analyzing the statistics of the
      hydrogen bonds, we identify that only 34% of the configurations give symmetric
      distributions around the two hydroxyls of the H2O2 simultaneously. The magnetic
      shieldings and the indirect spin-spin coupling constants were calculated at the
      B3LYP/aug-cc-pVTZ and aug-cc-pVTZ-J computational level. We find that the solvent
      shields the oxygen and unshields the hydrogen atoms of the peroxide (+5.5 and 
      2.9 ppm, respectively), with large fluctuation from configuration to
      configuration in the oxygen case, an effect largely accounted for in terms of a
      single hydrogen bond with H2O2 as the proton donor. The most sensitive coupling
      in the presence of the solvent is observed to be the one-bond J(O,H). 

PMID- 25046575
TI  - Ejaculatory dysfunction after treatment for lower urinary tract symptoms:
      retrograde ejaculation or retrograde thinking?

PMID- 25046574
TI  - Familial aggregation of candidate phenotypes for borderline personality disorder.
AB  - Borderline personality disorder (BPD) and its core Diagnostic and Statistical
      Manual of Mental Disorders (DSM) factor-analytically derived phenotypes aggregate
      in families. To potentially inform future conceptualizations of BPD, this study
      examined the familial aggregation and co-aggregation with BPD of 3 additional
      candidate phenotypes for BPD psychopathology: anxiousness, aggressiveness, and
      cognitive dysregulation. Participants included 347 probands (126 with BPD, 128
      without BPD, and 93 with major depressive disorder) and 814 parents and siblings
      of probands. All participants completed diagnostic assessments and scales
      assessing the candidate phenotypes. The familial aggregation of phenotypes
      (correlation of level of phenotype between family members), the familial co
      aggregation of phenotypes with BPD (correlation of phenotype with BPD between
      family members), and the within-individual correlation of phenotypes with BPD
      were assessed. All 3 candidate phenotypes showed high levels of familial
      aggregation (rs = .14 - .53, ps < .001), the magnitudes of which were comparable
      with DSM-based core sectors of psychopathology. Anxiousness and cognitive
      dysregulation showed strong within-individual associations with BPD (rs = .55 and
      .46, respectively; ps < .001) and substantial familial co-aggregation with BPD
      (rs = .12 and .13, respectively; ps <= .002). In contrast, aggressiveness showed
      a weak within-individual association with BPD (r = .11, p = .12) and little
      familial co-aggregation with BPD (r = .05, p = .21). These findings suggest that
      anxiousness and cognitive dysregulation are promising phenotypes for BPD
      psychopathology that move beyond factor-analytically based conceptualizations. In
      contrast, aggressiveness was only weakly related to BPD, suggesting that this
      phenotype may not represent an essential feature of this disorder.

PMID- 25046576
TI  - Monoterpenoid coumarins from the peels of Clausena lansium.
AB  - A phytochemical investigation on the peels of Clausena lansium (Lour.) Skeels led
      to the isolation of two new monoterpenoid coumarins, named clauslactone V (1) and
      clauslactone W (2), together with three known analogues (3-5). Their structures
      were elucidated by spectroscopic techniques (UV, IR, MS, 1D and 2D NMR). All the
      compounds were evaluated for hypoglycemic activity, and compounds 1-5 showed
      alpha-glucosidase inhibitory activity in vitro. 

PMID- 25046577
TI  - Low CO2 results in a rearrangement of carbon metabolism to support C4
      photosynthetic carbon assimilation in Thalassiosira pseudonana.
AB  - The mechanisms of carbon concentration in marine diatoms are controversial. At
      low CO2 , decreases in O2 evolution after inhibition of phosphoenolpyruvate
      carboxylases (PEPCs), and increases in PEPC transcript abundances, have been
      interpreted as evidence for a C4 mechanism in Thalassiosira pseudonana, but the
      ascertainment of which proteins are responsible for the subsequent
      decarboxylation and PEP regeneration steps has been elusive. We evaluated the
      responses of T. pseudonana to steady-state differences in CO2 availability, as
      well as to transient shifts to low CO2 , by integrated measurements of
      photosynthetic parameters, transcript abundances and quantitative proteomics. On
      shifts to low CO2 , two PEPC transcript abundances increased and then declined on
      timescales consistent with recoveries of Fv /Fm , non-photochemical quenching
      (NPQ) and maximum chlorophyll a-specific carbon fixation (Pmax ), but transcripts
      for archetypical decarboxylation enzymes phosphoenolpyruvate carboxykinase
      (PEPCK) and malic enzyme (ME) did not change. Of 3688 protein abundances
      measured, 39 were up-regulated under low CO2 , including both PEPCs and pyruvate
      carboxylase (PYC), whereas ME abundance did not change and PEPCK abundance
      declined. We propose a closed-loop biochemical model, whereby T. pseudonana
      produces and subsequently decarboxylates a C4 acid via PEPC2 and PYC,
      respectively, regenerates phosphoenolpyruvate (PEP) from pyruvate in a pyruvate
      phosphate dikinase-independent (but glycine decarboxylase (GDC)-dependent)
      manner, and recuperates photorespiratory CO2 as oxaloacetate (OAA).

PMID- 25046578
TI  - The effect of narrative writing on maternal stress in neonatal intensive care
      settings.
AB  - OBJECTIVE: This study was conducted to examine the effect of narrative writing on
      maternal stress in the Neonatal Intensive Care Units (NICUs) during infants'
      hospitalization. METHODS: A quasi-experimental study was conducted among 2 groups
      of mothers with preterm infants in the NICUs of two teaching hospitals of Tehran
      University of Medical Sciences. Pre- and post-tests were administered to a sample
      size of 70 during 6 months. The Parental Stressor Scale (PSS) was used. The data
      were analyzed using descriptive and analytical statistical methods. RESULTS: The
      mean stress level in the control group was 73.9 +/- 16.7 at the beginning of the
      study, and 82.5 +/- 19.5 at the end of the study (on the 10th day). Paired t-test
      results in the control group showed that there was a statistically significant
      difference between the 3rd and the 10th day of the hospitalization (p < 0.001).
      In the intervention group, the mean stress level at the beginning of the study
      and on the 10th day of the hospitalization was 78.9 +/- 16 and 48.8 +/- 14.1,
      respectively (p < 0.001). The results revealed statistically significant
      difference between the 2 groups on the 10th day of the study (p < 0.001).
      CONCLUSION: According to the findings, the narrative writing may be considered as
      an efficient supportive intervention to reduce the maternal stress in the NICUs.
      However, more research is needed to justify its implementation.

PMID- 25046579
TI  - Second trimester amniotic fluid glucose, uric acid, phosphate, potassium, and
      sodium concentrations in relation to maternal pre-pregnancy BMI and birth weight
      centiles.
AB  - OBJECTIVE: To study the evolution profile of amniotic fluid (AF) glucose, uric
      acid, phosphate, potassium, and sodium, in the second trimester of pregnancy, and
      explore the possible relations between the concentration of these components and
      maternal, as well as neonatal characteristics. METHODS: AF of 52 pregnant women
      was analyzed using an automatic multichannel analyzer. Maternal age, pre
      pregnancy Body Mass Index (BMI), inter-pregnancy intervals, and smoking status
      were derived from questionnaires. Information on pregnancy and delivery was
      collected from medical records. RESULTS: Uric acid increased (r = 0.423, p <
      0.01), while phosphate and glucose concentrations decreased during the period of
      16-26th week of pregnancy (r = -0.590, p < 0.001 and r = -0.314, p < 0.05,
      respectively). Maternal pre-pregnancy BMI was significantly correlated with AF
      uric acid concentration (r = 0.460, p < 0.01) and marginally with AF glucose (r =
      0.274, p = 0.052) and sodium (r = 0.254, p = 0.070) levels. Multiple linear
      regression indicated that mid-trimester AF uric acid and phosphate levels were
      significantly related to birth weight centiles (R(2)( )= 0.345, p < 0.05).
      CONCLUSIONS: Our results suggest that: (a) AF phosphate levels reflect
      gestational age to a satisfactory extent, (b) maternal pre-pregnancy BMI is
      significantly correlated with AF uric acid concentration, and (c) in appropriate
      for gestational age infants, AF phosphate and uric acid levels may serve as
      potential biomarkers of birth weight centiles. Further studies on AF composition
      may help to unravel the biochemical pathways underlying fetal development and
      could offer insight on the potential impact of maternal nutritional management on
      fetal growth regulation.

PMID- 25046580
TI  - Graphene oxide as a water dissociation catalyst in the bipolar membrane
      interfacial layer.
AB  - Bipolar membranes are formed by the lamination of an anion- and cation-exchange
      layer. Upon a sufficient applied reverse bias, water molecules at the layer
      junction dissociate, generating OH(-) and H(+), which can be useful in
      electrodialysis and electrosynthesis applications. Graphene oxide has been
      introduced into bipolar membrane junctions (illustrated in the adjacent graphic)
      and is shown to be an efficient new water dissociation catalyst, lowering the
      overpotential by 75% compared to a control membrane. It was found that adjusting
      deposition conditions changes the nature of the graphene oxide films, leading to
      tunable membrane performance. Additionally, it is shown that their low
      overpotentials are stable, making for industrially viable, high-performance
      bipolar membranes. 

PMID- 25046581
TI  - Physics and technological aspects of nanofluidics.
AB  - From a physical perspective, nanofluidics represents an extremely rich domain. It
      hosts many mechanisms acting on the nanoscale, which combine together or interact
      with the confinement to generate new phenomena. Superfast flows in carbon
      nanotubes, nonlinear electrokinetic transport, slippage over smooth surfaces,
      nanobubble stability, etc. are the most striking phenomena that have been
      unveiled over the past few years, and some of them are still awaiting an
      explanation. One may anticipate that new nanofluidic effects will be discovered
      in the future, but at the moment, the technological barrier is high. Fabrication
      of nanochannels is most often a tour de force, slow and costly. However, with the
      accumulation of technological skills along with the use of new nanofluidic
      materials (like nanotubes), nanofluidics is becoming increasingly accessible to
      experimentalists. Among the technological challenges faced by the field,
      fabricating devices mimicking natural nanometric systems, such as aquaporins,
      ionic pumps or kidney osmotic filtering, seems the most demanding in terms of
      groundbreaking ideas. Nanoflow characterization remains delicate, although
      considerable progress has been achieved over the past years. The targeted
      application of nanofluidics is not only in the field of genomics and membrane
      science--with disruptive developments to be expected for water purification,
      desalination, and energy harvesting--but also for oil and gas production from
      unconventional reservoirs. Today, in view of the markets that are targeted,
      nanofluidics may well impact the industry more than microfluidics; this would
      represent an unexpected paradox. These successes rely on using a variety of
      materials and technologies, using state-of-the-art nanofabrication, or low-tech
      inexpensive approaches. As a whole, nanofluidics is a fascinating field that is
      facing considerable challenges today. It possesses a formidable potential and
      offers much space for creative groundbreaking ideas.

PMID- 25046583
TI  - Palladium-catalyzed direct C7-arylation of substituted indazoles.
AB  - A novel direct C7-arylation of indazoles with iodoaryls is described using
      Pd(OAc)2 as catalyst, 1,10-phenanthroline as ligand, and K2CO3 as base in
      refluxing DMA. Direct C7-arylation of 3-substituted 1H-indazole containing an EWG
      on the arene ring gave the expected products in good isolated yields. In
      addition, a one-pot Suzuki-Miyaura/arylation procedure leading to C3,C7
      diarylated indazoles has been developed. 

PMID- 25046582
TI  - Screening of plants from diversified natural grasslands for their potential to
      combine high digestibility, and low methane and ammonia production.
AB  - A total of 156 plant species from 35 botanical families collected from
      diversified grasslands in the French Massif Central were screened in vitro for
      their potential to combine high nutritive value for ruminants and a reduced
      impact on the environment. The vegetative part of plants were analyzed for their
      chemical composition and incubated in a batch system containing buffered rumen
      fluid at 39 degrees C for 24 h. The gas production and composition were recorded,
      and the fermentation end-product concentrations in the incubation medium and the
      in vitro true organic matter digestibility (IVTOMD) were determined. The results
      were expressed relative to perennial ryegrass (PRG) values used as a reference.
      We observed that no relationship between methane (CH4) and volatile fatty acids
      (VFA) was evidenced for 12 plants, the fermentation of these plants producing
      significantly less CH4 for a similar level of VFA production. In all, 13 plants
      showed 50% less CH4 production per unit of organic matter truly digested (OMTD)
      than PRG. Among these plants, two reduced CH4 by more than 80% and four species
      had an IVTOMD higher than 80%. The underlying modes of action seem to be
      different among plants: some result in an accumulation of H2 in the fermentation
      gas, but others do not. In terms of nitrogen (N) use efficiency, the fermentation
      of 37 plants halved the ratio between ammonia (N-NH3) and plant N content
      compared with PRG, of which six showed a complete absence of N-NH3 in the medium.
      Among these plants, four maintained the IVTDMO at values not significantly
      different from PRG (P>0.05). Considering the multi-criteria selection, 16 plants
      showed simultaneously a reduction of more than 80% in N-NH3 production and 30% in
      CH4 emission per unit of OMTD compared with PRG, including three with an IVTOMD
      higher than 80%. Overall, the botanical families that reduced simultaneously CH4
      and N-NH3 most efficiently were the Rosaceae, Onagraceae, Polygonaceae and
      Dipsacaceae. The Onagraceae also gave high values for IVTOMD. 

PMID- 25046584
TI  - Laser ablation in the management of obstructive uropathy in neonates.
AB  - INTRODUCTION: Endoscopic management of posterior urethral valves and congenital
      ureteroceles is the current standard to relieve the obstruction. While the most
      commonly used techniques involve cystoscopic incision with cold knife or
      electrosurgery, an alternative is to ablate the obstructive tissue with laser
      energy. With increasing prenatal diagnoses, there has been an increasing shift in
      the timing of intervention toward earlier periods. The literature contains only
      two reports of laser ablation in neonates for these disease entities. MATERIALS
      AND METHODS: A case series was conducted by retrospectively reviewing our
      surgical database for all consecutive infants <28 days old (i.e., neonates)
      diagnosed in utero with obstructive uropathy and with postnatal imaging
      consistent with either urethral valves (anterior or posterior) or ureterocele.
      Holmium: yttrium aluminum-garnet (Ho:YAG) laser ablation was used as the
      exclusive modality of endoscopic management during the study period. All patients
      were followed with voiding cystourethrogram and renal/bladder ultrasounds
      postoperatively. RESULTS: Seventeen neonates underwent retrograde transurethral
      laser ablation procedures at a median age of 7 days (range 3-27). There were nine
      cases of urethral valve ablation (seven posterior, two anterior) and eight
      ureterocele ablations. Median operative time was 23 minutes (range 18-33). There
      were no intraoperative complications or reoperative procedures required for any
      case. All patients voided after postoperative catheter removal, and no patient
      had evidence of residual valve tissue or urethral stricture at mean follow-up of
      10.1 months. All patients with ureterocele demonstrated partial or complete
      decompression of the ureterocele and improvement in hydroureteronephrosis at 3
      months. CONCLUSIONS: Ho:YAG laser ablation appears safe, effective, and efficient
      for the management of urethral valves and ureteroceles in the neonatal period.
      With a continuing trend toward early definitive intervention for these
      conditions, laser ablation remains an important alternative to electrosurgery in
      this population.

PMID- 25046585
TI  - Real-time observation of atomic layer deposition inhibition: metal oxide growth
      on self-assembled alkanethiols.
AB  - Through in situ quartz crystal microbalance (QCM) monitoring, we resolve the
      growth of a self-assembled monolayer (SAM) and subsequent metal oxide deposition
      with high resolution. We introduce the fitting of mass deposited during each
      atomic layer deposition (ALD) cycle to an analytical island-growth model that
      enables quantification of growth inhibition, nucleation density, and the
      uninhibited ALD growth rate. A long-chain alkanethiol was self-assembled as a
      monolayer on gold-coated quartz crystals in order to investigate its
      effectiveness as a barrier to ALD. Compared to solution-loading, vapor-loading is
      observed to produce a SAM with equal or greater inhibition ability in minutes vs
      days. The metal oxide growth temperature and the choice of precursor also
      significantly affect the nucleation density, which ranges from 0.001 to 1
      sites/nm(2). Finally, we observe a minimum 100 cycle inhibition of an oxide ALD
      process, ZnO, under moderately optimized conditions. 

PMID- 25046586
TI  - Numerical study of vapor condensation on patterned hydrophobic surfaces using the
      string method.
AB  - Vapor condensation on solid surfaces plays a crucial role across a wide range of
      industrial applications. Recent advances of nanotechnology have made possible the
      manipulation of the condensation process through the control of surface
      structures. In this work, we study vapor condensation on hydrophobic surfaces
      patterned with microscale pillars. The critical nuclei, the activation barriers,
      and the minimum energy paths are computed using the climbing string method. The
      effects of pillar height, interpillar spacing, the level of supersaturation, and
      the intrinsic wettability of the solid surface on the nucleation process are
      investigated. Two nucleation scenarios are obtained from the computation. In the
      case of high pillar, narrow interpillar spacing, low supersaturation, and/or low
      surface wettability, the critical nucleus prefers the suspended Cassie state;
      otherwise, it prefers the impaled Wenzel state. A comparison of the nucleation
      barrier with that on a flat surface of the same material reveals that vapor
      condensation is inhibited by the microstructures in the former case, while
      enhanced in the latter case. The critical values of the pillar height, the
      interpillar spacing, and the supersaturation at which the critical nucleus
      changes from the Cassie state to the Wenzel state are identified from the phase
      diagram of the critical nucleus. It is found that the dependence of the critical
      interpillar spacing on the supersaturation follows closely the curve of the
      critical radii in a homogeneous nucleation. The relaxation dynamics of the
      condensate after the critical nucleus is formed is computed by solving the
      steepest descent equation. It is observed that when the pillar is low and/or the
      interpillar spacing is wide, a condensate initially in the Cassie state may
      evolve into the Wenzel state during the relaxation. 

PMID- 25046587
TI  - Aggregation and segregation of confined active particles.
AB  - We simulate a model of self-propelled disks with soft repulsive interactions
      confined to a box in two dimensions. For small rotational diffusion rates,
      monodisperse disks spontaneously accumulate at the walls. At low densities,
      interaction forces between particles are strongly inhomogeneous, and a simple
      model predicts how these inhomogeneities alter the equation of state. At higher
      densities, collective effects become important. We observe signatures of a
      jamming transition at a packing fraction phi ~ 0.88, which is also the jamming
      point for non-active athermal monodisperse disks. At this phi, the system
      develops a critical finite active speed necessary for wall aggregation. At
      packing fractions above phi ~ 0.6, the pressure decreases with increasing
      density, suggesting that strong interactions between particles are affecting the
      equation of state well below the jamming transition. A mixture of bidisperse
      disks segregates in the absence of any adhesion, identifying a new mechanism that
      could contribute to cell sorting in embryonic development. 

PMID- 25046588
TI  - Macrophage CD14 expression in human carotid plaques is associated with
      complicated lesions, correlates with thrombosis, and is reduced by angiotensin
      receptor blocker treatment.
AB  - CD14 is a predictor of inflammation and associated with atherosclerosis. We
      analyzed 118 carotid plaques from patients with symptomatic carotid artery
      stenosis for expression of the macrophage markers CD14, CD68 and the angiotensin
      II type 1 receptor (AT1-R). CD14 staining was significantly increased in
      thrombotic carotid plaques. AT1-R staining was found in macrophage-rich areas,
      and AT1-R mRNA was detected in plaque macrophages isolated with anti-CD14
      immunobeads. In patients treated with an angiotensin receptor blocker, expression
      of CD14 and CD68 in carotid plaque and serum levels of inflammatory markers were
      lower than in untreated patients. In vitro, expression of CD14 in human monocyte
      derived macrophages was increased by exposure to lipopolysaccharide and decreased
      by exposure to an angiotensin receptor blocker. Thus, inhibition of the innate
      immune responsive lipopolysaccharide receptor CD14 in macrophages, rather than
      AT1-R inhibition, may help explain the anti-inflammatory effects of angiotensin
      receptor blockade. 

PMID- 25046589
TI  - Role of alpha-lipoic acid in LPS/d-GalN induced fulminant hepatic failure in
      mice: studies on oxidative stress, inflammation and apoptosis.
AB  - This study investigated the protective effect of alpha-lipoic acid (LA) on
      lipopolysaccharide (LPS)/d-galactosamine (d-GalN)-induced fulminant hepatic
      failure in mice. First, we found that LA markedly reduced LPS/d-GalN-induced
      increases in serum ALT and AST activities, which were supplemented with
      histopathological examination, suggested that LA has a protective effect on this
      model of hepatic damage. Livers challenged with LPS/d-GalN exhibited extensive
      areas of vacuolization with the disappearance of nuclei and the loss of hepatic
      architecture. On the contrary, these pathological alterations were ameliorated by
      LA treatment. Next, we found that ROS and TBARS levels were increased in LPS/d
      GalN treated liver homogenates, which were attenuated by LA administration.
      Consistently, decreases in hepatic CAT and GPx activities were observed in LPS/d
      GalN group and were significantly restored by LA administration. Moreover,
      pretreatment with LA markedly reduced LPS/d-GalN-induced iNOS, COX-2, TNF-alpha,
      NF-kappaB, IL-1beta and IL-6 expressions. Furthermore, our data showed that TUNEL
      positive cells increased in LPS/d-GalN-treated mice liver which was counteracted
      by LA administration. LPS/d-GalN induced apoptosis of hepatocytes, as estimated
      by caspase 3, caspase 8 and caspase 9 activations. Also, the increasing of Bax
      and the decreasing of Bcl-2 expressions also supported LPS/d-GalN induced
      apoptosis. Interestingly, LA marked relieved these apoptotic features. Taking
      together, our results indicated that LA plays an important role on LPS/d-GalN
      induced fulminant hepatic failure through its antioxidant, anti-inflammatory and
      anti-apoptotic activities. 

PMID- 25046590
TI  - Selection and evaluation of optimal two-dimensional CAIPIRINHA kernels applied to
      time-resolved three-dimensional CE-MRA.
AB  - PURPOSE: To develop and validate a method for choosing the optimal two
      dimensional CAIPIRINHA kernel for subtraction contrast-enhanced MR angiography
      (CE-MRA) and estimate the degree of image quality improvement versus that of some
      reference acceleration parameter set at R >= 8. METHODS: A metric based on
      patient-specific coil calibration information was defined for evaluating
      optimality of CAIPIRINHA kernels as applied to subtraction CE-MRA. Evaluation in
      retrospective studies using archived coil calibration data from abdomen, calf,
      foot, and hand CE-MRA exams was accomplished with an evaluation metric comparing
      the geometry factor (g-factor) histograms. Prospective calf, foot, and hand CE
      MRA studies were evaluated with vessel signal-to-noise ratio (SNR). RESULTS:
      Retrospective studies show g-factor improvement for the selected CAIPIRINHA
      kernels was significant in the feet, moderate in the abdomen, and modest in the
      calves and hands. Prospective CE-MRA studies using optimal CAIPIRINHA show
      reduced noise amplification with identical acquisition time in studies of the
      feet, with minor improvements in the hands and calves. CONCLUSION: A method for
      selection of the optimal CAIPIRINHA kernel for high (R >= 8) acceleration CE-MRA
      exams given a specific patient and receiver array was demonstrated. CAIPIRINHA
      optimization appears valuable in accelerated CE-MRA of the feet and to a lesser
      extent in the abdomen.

PMID- 25046592
TI  - Interspecific variation in the microanatomy of cosmetid harvestmen (Arachnida,
      Opiliones, Laniatores).
AB  - Scanning electron microscopy (SEM) is a useful tool for identifying interspecific
      variation in often overlooked structures that may represent useful sources for
      informative phylogenetic characters. In this study, we used SEM to compare the
      morphology of 12 cosmetid species from Central America, the Caribbean, and North
      America including multiple species for the genera Cynorta, Erginulus, and
      Paecilaema. To determine if microanatomical structures were unique to the
      cosmetid taxa under examination, we investigated the microanatomical structures
      of six additional species of gonyleptoidean harvestmen representing the families
      Agoristenidae, Cranaidae, Gonyleptidae, Manaosbiidae, and Stygnidae. Our results
      indicate that the shape of the ocularium (narrow, intermediate, or broad) did not
      vary within cosmetid genera, whereas the morphology of the rough pit glands on
      the eye mound varied considerably between species. Each cosmetid species had 10
      20 rough pit glands on the ocularium whereas only the eye mounds of Avima
      intermedia (Agoristenidae) and Glysterus sp. (Gonyleptidae) had similar
      structures. With regards to the surface texture of the dorsal scutum, cosmetid
      harvestmen exhibited a rivulose-microgranulate morphology (6 species), a
      microtuberculate-rivulose-microrgranulate morphology (4 species), or a
      microgranulate morphology (2 species). In contrast, each of the gonyleptoidean
      species exhibited a microgranulate pattern, with the exception of Stygnoplus
      clavotibialis, which had a rivulose-microgranulate surface texture. For cosmetid
      harvestmen, we observed considerable interspecific variation in the shape and
      number of teeth on the fixed and moveable fingers of the male chelicerae.
      Similarly, we also observed interspecific variation in the distribution and shape
      of tubercles on the ventral and dorsal surfaces of the femur of the pedipalp.
      Overall, our results indicate that there are several microanatomical structures
      associated with the ocularium, dorsal scutum, male chelicera, and pedipalp that
      could represent informative phylogenetic characters in future taxonomic studies
      of cosmetid harvestmen.

PMID- 25046593
TI  - Involvement of the brain renin-angiotensin system (RAS) in the neuroadaptive
      responses induced by amphetamine in a two-injection protocol.
AB  - A single or repeated exposure to psychostimulants induces long-lasting
      neuroadaptative changes. Different neurotransmitter systems are involved in these
      responses including the neuropeptide angiotensin II. Our study tested the
      hypothesis that the neuroadaptative changes induced by amphetamine produce
      alterations in brain RAS components that are involved in the expression of the
      locomotor sensitization to the psychostimulant drug. Wistar male rats, pretreated
      with amphetamine were used 7 or 21 days later to study AT1 receptors by
      immunohistochemistry and western blot and also angiotensinogen mRNA and protein
      in caudate putamen and nucleus accumbens. A second group of animals was used to
      explore the possible role of Ang II AT1 receptors in the expression of behavioral
      sensitization. In these animals treated in the same way, bearing intra-cerebral
      cannula, the locomotor activity was tested 21 days later, after an amphetamine
      challenge injection and the animals received an AT1 blocker, losartan, or saline
      5min before the amphetamine challenge. An increase of AT1 receptor density
      induced by amphetamine was found in both studied areas and a decrease in
      angiotensinogen mRNA and protein only in CPu at 21 days after treatment;
      meanwhile, no changes were established in NAcc. Finally, the increased locomotor
      activity induced by amphetamine challenge was blunted by losartan administration
      in CPu. No differences were detected in the behavioral sensitization when the AT1
      blocker was injected in NAcc. Our results support the hypothesis of a key role of
      brain RAS in the neuroadaptative changes induced by amphetamine. 

PMID- 25046596
TI  - Coffee components and cardiovascular risk: beneficial and detrimental effects.
AB  - Coffee consists of several biological active compounds, such as caffeine,
      diterpenes, chlorogenic acids, and melanoidins, which may affect human health.
      The intake of each compound depends on the variety of coffee species, roasting
      degree, type of brewing method and serving size. The bioavailability and the
      distribution of each compound and its metabolites also contribute to coffee
      mechanisms of action. The health benefits of coffee consumption regarding
      cardiovascular system and metabolism mostly depend on its antioxidant compounds.
      In contrast, diterpenes and caffeine may produce harmful effects by raising lipid
      fraction and affecting endothelial function, respectively. Studying the mechanism
      of action of coffee components may help understanding weather coffee's impact on
      health is beneficial or hazardous. In this article, we reviewed the available
      information about coffee compounds and their mechanism of action. Furthermore,
      benefits and risks for cardiovascular system associated with coffee consumption
      will be discussed.

PMID- 25046597
TI  - Second trimester maternal serum alpha-fetoprotein (MSAFP) as predictor of fetal
      hemoglobin Bart's disease.
AB  - OBJECTIVE: The objective of this study is to evaluate the efficacy of maternal
      serum alpha-fetoprotein (MSAFP) levels in predicting hemoglobin (Hb) Bart's
      fetus. MATERIALS AND METHODS: A total of 199 pregnancies at risk of fetal Hb
      Bart's disease at 18 to 22 weeks were enrolled. Before performing cordocentesis
      for the Hb typing analysis, the MSAFP levels were analyzed, and sonographic
      markers (middle cerebral artery peak systolic velocity, cardiothoracic ratio and
      placental thickness) were measured. The detection rates of MSAFP and the
      sonographic markers in predicting fetuses affected by Hb Bart's disease were
      evaluated. RESULTS: The MSAFP levels were significantly higher in pregnant women
      carrying affected fetuses (47 cases) than in those with unaffected fetuses (2.09
      MoM vs 1.18 MoM, P < 0.001). MSAFP as a single marker effectively predicted fetal
      Hb Bart's disease (area under curve receiver operating characteristic 0.832, 95%
      CI 0.752-0.911), with 87.2% sensitivity and 74.5% specificity using a cutoff
      value greater than 1.50 MoM. A combination of MSAFP with sonographic markers gave
      detection rates in the range of 91.5% to 100%. CONCLUSION: Second trimester MSAFP
      levels are significantly higher in pregnancies with Hb Bart's fetus. MSAFP as a
      single marker is relatively effective in Hb Bart's prenatal screening. A high
      detection rate is achieved when MSAFP is used in combination with sonographic
      markers.

PMID- 25046599
TI  - Obesity and genitourinary cancer risks.

PMID- 25046600
TI  - Renal surgery and its impact on chronic kidney disease: a continuing evolution in
      decision making.

PMID- 25046601
TI  - Renal oncocytosis.

PMID- 25046603
TI  - Urothelial carcinoma of the upper urinary tract.

PMID- 25046604
TI  - Tissue engineering of the bladder--when will we get there?

PMID- 25046605
TI  - Loading of ionic compounds into metal-organic frameworks: a joint theoretical and
      experimental study for the case of La3+.
AB  - Crystalline, highly orientated surface-anchored MOF thin films, grown on Au
      substrates, were prepared using liquid-phase epitaxy (LPE). The successful
      loading of La(3+) ions into the Cu3(BTC)2 (HKUST-1) SURMOFs (surface-mounted
      metal-organic frameworks) was monitored using X-ray diffraction (XRD).
      Theoretical calculations using classical force-field based Monte Carlo
      simulations yield a structure with two La(3+) ions within the large Cu3(BTC)2
      pores, in full agreement with experimental results on the composition of these
      films and the relative intensities of the XRD peaks. Implications of these
      findings for using MOF thin films for electronic applications are briefly
      discussed. 

PMID- 25046606
TI  - Ipilimumab: a potential immunologic agent in the treatment of metastatic
      castration-resistant prostate cancer.
AB  - Immunotherapy has garnered an important place in the therapeutic landscape of
      treatment in prostate cancer since approval of sipuleucel-T. Ipilimumab is a
      checkpoint inhibitor that is currently approved for the treatment of advanced
      melanoma. In the June issue of Lancet Oncology, Kwon and colleagues report the
      phase III trial using ipilimumab in a post-docetaxel metastatic castration
      resistant prostate cancer population. While the primary endpoint of overall
      survival was not met, several lessons are learned from the analysis of this
      trial. Perhaps better refinement of a more favorable group of patients who may
      potentially benefit from an immunologic treatment should be advocated. 

PMID- 25046607
TI  - National study of illicit drug use in Slovakia based on wastewater analysis.
AB  - The aim of this study was to analyze illicit drugs and their metabolites in
      wastewater from eight selected wastewater treatment plants (WWTPs) in Slovakia.
      The effect of two of the biggest music festivals in Slovakia on illicit drugs in
      wastewater was also investigated. Urinary bio-markers of amphetamine,
      methamphetamine, cocaine, cannabis and ecstasy use were analyzed by liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS). We then compared
      our results with data obtained in other parts of Europe and the world. This study
      demonstrates that Slovakia has one of highest methamphetamine consumption rates
      in Europe. Within Slovakia, the highest level of methamphetamine consumption was
      found in Petrzalka, where the mean specific load of this drug in sewage was 169
      mg/day/1000 inhabitants; the next highest loads were detected in Piestany (128
      mg/day/1000 inhabitants) and Bratislava (124 mg/day/1000 inhabitants).
      Amphetamine, ecstasy and cannabis consumption in our study were comparable to
      that found in other European cities, whereas cocaine consumption was lower. We
      also analyzed the pattern of drug consumption over the course of a week. The load
      of the cocaine metabolite benzoylecgonine in wastewater increased during the
      weekend. The use of this drug was most common in the capital of Slovakia.
      Increased consumption was also found during a folk festival in Piestany. The
      ecstasy load in wastewater from larger cities also significantly increased over
      the weekend. An increase of drug consumption was also detected during a music
      festival in Trencin, especially for ecstasy. The specific load of ecstasy during
      this festival increased from 3mg/day/1000 inhabitants to 29 mg/day/1000
      inhabitants. The possible influence of music styles on the consumption of certain
      drugs was also observed. During a folk festival, methamphetamine and cocaine were
      more commonly used.

PMID- 25046608
TI  - Flux measurements in the surface Marine Atmospheric Boundary Layer over the
      Aegean Sea, Greece.
AB  - Micro-meteorological measurements within the surface Marine Atmospheric Boundary
      Layer took place at the shoreline of two islands at northern and south-eastern
      Aegean Sea of Greece. The primary goal of these experimental campaigns was to
      study the momentum, heat and humidity fluxes over this part of the north-eastern
      Mediterranean Sea, characterized by limited spatial and temporal scales which
      could affect these exchanges at the air-sea interface. The great majority of the
      obtained records from both sites gave higher values up to factor of two, compared
      with the estimations from the most widely used parametric formulas that came
      mostly from measurements over open seas and oceans. Friction velocity values from
      both campaigns varied within the same range and presented strong correlation with
      the wind speed at 10 m height while the calculated drag coefficient values at the
      same height for both sites were found to be constant in relation with the wind
      speed. Using eddy correlation analysis, the heat flux values were calculated
      (virtual heat fluxes varied from -60 to 40 W/m(2)) and it was found that they are
      affected by the limited spatial and temporal scales of the responding air-sea
      interaction mechanism. Similarly, the humidity fluxes appeared to be strongly
      influenced by the observed intense spatial heterogeneity of the sea surface
      temperature.

PMID- 25046609
TI  - Beyond the transect: an alternative microchemical imaging method for fine scale
      analysis of trace elements in fish otoliths during early life.
AB  - Microchemical analysis of otolith (calcified 'ear stones' used for balance and
      orientation) of fishes is an important tool for studying their environmental
      history and management. However, the spatial resolution achieved is often too
      coarse to examine short-term events occurring in early life. Current methods rely
      on single points or transects across the otolith surface, which may provide a
      limited view of elemental distributions, a matter that has not previously been
      investigated. Imaging by laser ablation-inductively coupled plasma-mass
      spectrometry (LA-ICP-MS) permits microchemical analyses of short-term events in
      early life with high (<10 MUm) resolution, two-dimensional (2D) visualization of
      elemental distributions. To demonstrate the potential of this method, we mapped
      the concentrations of Sr and Ba, two key trace elements, in a small number of
      juvenile otoliths of neon damselfish (Pomacentrus coelestis) using an 8 MUm beam
      diameter (laser fluence of 13.8 +/- 3.5 Jcm(-2)). Quantification was performed
      using the established method by Longerich et al. (1996), which is applied to 2D
      imaging of a biological matrix here for the first time. Accuracy of >97% was
      achieved using a multi-point non matrix-matched calibration of National Institute
      of Standards and Technology (NIST) 610 and 612 (trace elements in glass) using
      Longerich's calculation method against the matrix-matched standard FEBS-1
      (powdered red snapper [Lutjanus campechanus] otolith). The spatial resolution
      achieved in the otolith corresponded to a time period of 2 +/- 1 days during the
      larval phase, and 4 +/- 1 days during the post-settlement juvenile phase. This
      method has the potential to improve interpretations of early life-history events
      at scales corresponding to specific events. While the images showed gradients in
      Sr and Ba across the larval settlement zone more clearly than single transects,
      the method proved sample homogeneity throughout the structure; demonstrating that
      2D scanning has no significant advantage over line scans.

PMID- 25046610
TI  - Sensitivity analyses of MAGIC modelled predictions of future impacts of whole
      tree harvest on soil calcium supply and stream acid neutralizing capacity.
AB  - Forest biofuel is a main provider of energy in Sweden and the market is expected
      to grow even further in the future. Removal of logging residues via harvest can
      lead to short-term acidification but the long-term effects are largely unknown.
      The objectives of this study were to 1) model the long-term effect of whole-tree
      harvest (WTH) on soil and stream water acidity and 2) perform sensitivity
      analyses by varying the amounts of logging residues, calcium (Ca(2+))
      concentrations in tree biomass and site productivity in nine alternate scenarios.
      Data from three Swedish forested catchments and the Model of Acidification of
      Groundwater in Catchments (MAGIC) were used to simulate changes in forest soil
      exchangeable Ca(2+) pools and stream water acid neutralizing capacity (ANC) at
      Gammtratten, Kindla and Aneboda. Large depletions in soil Ca(2+) supply and a
      reversal of the positive trend in stream ANC were predicted for all three sites
      after WTH. However, the magnitude of impact on stream ANC varied depending on
      site and the concentration of mobile strong acid anions. Contrary to common
      beliefs, the largest decrease in modelled ANC was observed at the well-buffered
      site Gammtratten. The effects at Kindla and Aneboda were much more limited and
      not large enough to offset the general recovery from acidification. Varying the
      tree biomass Ca(2+) concentrations exerted the largest impact on modelled
      outcome. Site productivity was the second most important variable whereas
      changing biomass amounts left on site only marginally affected the results. The
      outcome from the sensitivity analyses pointed in the same direction of change as
      in the base scenario, except for Kindla where soil Ca(2+) pools were predicted to
      be replenished under a given set of input data. The reliability of modelled
      outcome would increase by using site-specific Ca(2+) concentrations in tree
      biomass and field determined identification of site productivity. 

PMID- 25046611
TI  - Assessment of arsenic concentration in stream water using neuro fuzzy networks
      with factor analysis.
AB  - We propose a systematical approach to assessing arsenic concentration in a river
      through: important factor extraction by a nonlinear factor analysis; arsenic
      concentration estimation by the neuro-fuzzy network; and impact assessment of
      important factors on arsenic concentration by the membership degrees of the
      constructed neuro-fuzzy network. The arsenic-contaminated Huang Gang Creek in
      northern Taiwan is used as a study case. Results indicate that rainfall, nitrite
      nitrogen and temperature are important factors and the proposed estimation model
      (ANFIS(GT)) is superior to the two comparative models, in which 50% and 52%
      improvements in RMSE are made over ANFIS(CC) and ANFIS(all), respectively.
      Results reveal that arsenic concentration reaches the highest in an environment
      of lower temperature, higher nitrite nitrogen concentration and larger one-month
      antecedent rainfall; while it reaches the lowest in an environment of higher
      temperature, lower nitrite nitrogen concentration and smaller one-month
      antecedent rainfall. It is noted that these three selected factors are easy-to
      collect. We demonstrate that the proposed methodology is a useful and effective
      methodology, which can be adapted to other similar settings to reliably model
      water quality based on parameters of interest and/or study areas of interest for
      universal usage. The proposed methodology gives a quick and reliable way to
      estimate arsenic concentration, which makes good contribution to water
      environment management. 

PMID- 25046612
TI  - Emerging organic contaminants in vertical subsurface flow constructed wetlands:
      influence of media size, loading frequency and use of active aeration.
AB  - Four side-by-side pilot-scale vertical flow (VF) constructed wetlands of
      different designs were evaluated for the removal of eight widely used emerging
      organic contaminants from municipal wastewater (i.e. ibuprofen, acetaminophen,
      diclofenac, tonalide, oxybenzone, triclosan, ethinylestradiol, bisphenol A).
      Three of the systems were free-draining, with one containing a gravel substrate
      (VGp), while the other two contained sand substrate (VS1p and VS2p). The fourth
      system had a saturated gravel substrate and active aeration supplied across the
      bottom of the bed (VAp). All beds were pulse-loaded on an hourly basis, except
      VS2p, which was pulse-loaded every 2h. Each system had a surface area of 6.2m(2),
      received a hydraulic loading rate of 95 mm/day and was planted with Phragmites
      australis. The beds received an organic loading rate of 7-16 gTOC/m(2)d. The sand
      based VF (VS1p) performed significantly better (p<0.05) than the gravel-based
      wetland (VGp) both in the removal of conventional water quality parameters (TSS,
      TOC, NH4-N) and studied emerging organic contaminants except for diclofenac (85
      +/- 17% vs. 74 +/- 15% average emerging organic contaminant removal for VS1p and
      VGp, respectively). Although loading frequency (hourly vs. bi-hourly) was not
      observed to affect the removal efficiency of the cited conventional water quality
      parameters, significantly lower removal efficiencies were found for tonalide and
      bisphenol A for the VF wetland that received bi-hourly dosing (VS2p) (higher
      volume per pulse), probably due to the more reducing conditions observed in that
      system. However, diclofenac was the only contaminant showing an opposite trend to
      the rest of the compounds, achieving higher elimination rates in the wetlands
      that exhibited less-oxidizing conditions (VS2p and VGp). The use of active
      aeration in the saturated gravel bed (VAp) generally improved the treatment
      performance compared to the free-draining gravel bed (VGp) and achieved a similar
      performance to the free-draining sand-based VF wetlands (VS1p).

PMID- 25046613
TI  - Ultrastructural evaluation of shrinkage artefacts induced by fixatives and
      embedding resins on osteocyte processes and pericellular space dimensions.
AB  - The integrity of the interface between the osteocyte (Ot) process and the
      canalicular wall was investigated in terms of change in the lateral dimensions of
      the Ot process in relation to the canalicular width, i.e., widening of the
      pericellular space. This has been interpreted as shrinkage of the Ot process
      relative to the canalicular wall during sample preparation stages of fixation,
      dehydration, and resin embedding. Sprague-Dawley rat tibial cross-sections were
      prepared for transmission electron microscopy (TEM). Four different fixative
      preparations: paraformaldehyde (PF), modified Karnovsky's (MK), glutaraldehyde
      (GRR) with ruthenium red (GRR), and zinc formalin (ZF); and two different
      embedding resins: LR Gold (LRG) and Epon812 (Epon) were evaluated. It was found
      that for LRG embedding, formalin-only fixatives (PF and ZF) induced lower
      shrinkage than GRR-containing fixatives (MK and GRR). In contrast, for Epon
      embedding, MK showed the highest shrinkage, while no differences were found
      between the remaining fixatives (PF, ZF, and GRR). All formalin-containing
      fixatives (MK, PF, and ZF) induced similar shrinkage in both embedding media. The
      most dramatic difference was for GRR fixation, which in combination with LRG
      embedding showed ~ 62% more shrinkage than with Epon embedding, suggesting that
      the combination of GRR fixation and LRG embedding synergistically amplifies Ot
      shrinkage. These differences likely suggest a role of the resin in secondarily
      influencing the tissue structure following fixation. Further, the work confirms
      LRG as a poor embedding medium for bone specimens, as it causes large variations
      in shrinkage depending on fixation.

PMID- 25046614
TI  - Role of maternal tissue in the synthesis of polyunsaturated fatty acids in
      response to a lipid-deficient diet during pregnancy and lactation in rats.
AB  - During pregnancy and lactation, metabolic adaptations involve changes in
      expression of desaturases and elongases (Elovl2 and Elovl5) in the mammary gland
      and liver for the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs)
      such as arachidonic acid (AA) required for fetal and postnatal growth. Adipose
      tissue is a pool of LC-PUFAs. The response of adipose tissue for the synthesis of
      these fatty acids in a lipid-deficient diet of dams is unknown. The aim of this
      study was to explore the role of maternal tissue in the synthesis of LC-PUFAs in
      rats fed a low-lipid diet during pregnancy and lactation. Fatty acid composition
      (indicative of enzymatic activity) and gene expression of encoding enzymes for
      fatty acid synthesis were measured in liver, mammary gland and adipose tissue in
      rats fed a low-lipid diet. Gene expression of desaturases, elongases, fatty acid
      synthase (Fasn) and their regulator Srebf-1c was increased in the mammary gland,
      liver and adipose tissue of rats fed a low-lipid diet compared with rats from the
      adequate-lipid diet group throughout pregnancy and lactation. Genes with the
      highest (P<0.05) expression in the mammary gland, liver and adipose tissue were
      Elovl5 (1333%), Fads2 (490%) and Fasn (6608%), respectively, in a low-lipid diet
      than in adequate-lipid diet. The percentage of AA in the mammary gland was
      similar between the low-lipid diet and adequate-lipid diet groups during the
      second stage of pregnancy and during lactation. The percentage of monounsaturated
      and saturated fatty acids was significantly (P<0.05) increased throughout
      pregnancy and lactation in all tissues in rats fed a low-lipid diet than in rats
      fed an adequate-lipid diet. Results suggest that maternal metabolic adaptations
      used to compensate for lipid-deficient diet during pregnancy and lactation
      include increased expression of genes involved in LC-PUFAs synthesis in a stage-
      and tissue-specific manner and elevated lipogenic activity (saturated and
      monounsaturated fatty acid synthesis) of maternal tissues including adipose
      tissue. 

PMID- 25046615
TI  - Recent advancements in the cardiovascular drug carriers.
AB  - Cardiovascular disease is the disease that affects the cardiovascular system,
      vascular diseases of the brain and kidney, and peripheral arterial disease.
      Despite of all advances in pharmacological and clinical treatment, heart failure
      is a leading cause of morbidness and mortality worldwide. Many new therapeutic
      advance strategies, including cell transplantation, gene delivery or therapy, and
      cytokines or other small molecules, have been research to treat heart failure.
      The main aim of this review article is to focus on nano carriers advancement and
      addressing the problems associated with old and modern therapeutics such as
      nonspecific effects and poor stability. 

PMID- 25046616
TI  - Sunitinib, pazopanib or sorafenib for the treatment of patients with late
      relapsing metastatic renal cell carcinoma.
AB  - PURPOSE: Late recurrence of renal cell carcinoma is not a rare event. In this
      retrospective study we investigate the clinicopathological features and the
      outcome of patients treated with sorafenib, sunitinib and pazopanib for late
      relapsing renal cell carcinoma. MATERIALS AND METHODS: Data were collected from
      21 Italian centers involved in the treatment of metastatic renal cell carcinoma.
      Late relapse was defined as more than 5 years after initial radical nephrectomy.
      RESULTS: A total of 2,490 patients were screened and 269 (11%) were included in
      the study. First line therapy was sunitinib in 190 patients (71%), sorafenib in
      58 (21%) and pazopanib in 21 (8%). Median progression-free survival was 20.0
      months for sunitinib (95% CI 17.0-25.1), and 14.1 months for sorafenib (95% CI
      11.0-29.0) and pazopanib (95% CI 11.2-not reported). On multivariate analysis
      MSKCC score and metastases to lymph nodes, liver and brain were associated with
      worst overall survival, while pancreatic metastases were associated with longer
      survival. Furthermore, age, MSKCC score and brain metastases were associated with
      worst progression-free survival. CONCLUSIONS: Patients with late relapsing renal
      cell carcinoma seem to present a characteristic pattern of metastatic spread
      without showing significant differences in terms of progression-free survival
      among sorafenib, sunitinib and pazopanib.

PMID- 25046617
TI  - Primary and reoperative hypospadias repair in adults--are results different than
      in children?
AB  - PURPOSE: There is widespread belief that hypospadias surgery in adults has a
      greater urethroplasty complication rate than similar repair in children. We
      compared outcomes of primary and reoperative hypospadias repair in adults vs
      children. MATERIALS AND METHODS: We evaluated prospectively maintained databases
      of consecutive boys and adults, defined as Tanner 4 or greater, treated with
      primary or reoperative hypospadias repair from 2000 to 2013. We searched for
      urethroplasty complications, including fistula, glans dehiscence,
      stricture/stenosis and diverticulum. All operations were done with the goal of
      creating a neomeatus at the normal location at the tip of the glans. Univariate
      and multivariate analyses were done to determine whether pubertal status impacted
      urethroplasty complications. RESULTS: A total of 1,140 patients were operated on
      by a single surgeon, including 69 adults with a mean age of 23 years.
      Complications developed in 209 cases (18%), including 124 of 883 primary repairs
      (14%) and 85 of 257 reoperations (33%). There was no difference in outcomes
      between adults and children. Complications were noted in 1 of 8 men (12.5%) vs
      123 of 871 children (14%) with primary repair (p = 0.9) and in 16 of 61 (26%) vs
      69 of 196 (35%) with reoperation (p = 0.2). Multivariate analysis showed that a
      proximal meatus and reoperation were risk factors for complications but not
      pubertal status. CONCLUSIONS: In contrast to popular belief, our data do not
      indicate a greater risk for urethroplasty complications after hypospadias surgery
      performed in adulthood. Repair in adults can be done using the same techniques as
      in children with the same goal of a neomeatus at the tip of the glans.

PMID- 25046618
TI  - The risk of urinary tract infection after flexible cystoscopy in patients with
      bladder tumor who did not receive prophylactic antibiotics.
AB  - PURPOSE: The frequency of febrile urinary tract infection was determined after
      outpatient flexible cystoscopy in antibiotic naive patients with bladder tumor.
      MATERIALS AND METHODS: A total of 3,108 outpatient cystoscopies were performed in
      1,110 patients with bladder tumor. Immediately before cystoscopy patients
      submitted a voided urine sample for culture. Significant bacteriuria was defined
      as greater than 10(4) cfu/ml of a single organism. Patients received no
      antibiotics immediately before or after cystoscopy. They were followed for 30
      days for onset of febrile urinary tract infection. RESULTS: Of the 3,108 patient
      cystoscopies 673 (22%) had asymptomatic bacteriuria and 2,435 (78%) had sterile
      urine. A febrile urinary tract infection developed within 30 days of cystoscopy
      in 59 patients (1.9%), including in 3.7% of infected and 1.4% of uninfected
      patients (p = 0.01). All cases resolved within 12 to 24 hours with oral
      antibiotics. No patient was hospitalized for bacterial sepsis. CONCLUSIONS:
      Antibacterial therapy before outpatient flexible cystoscopy does not appear
      necessary in patients who have no clinical signs or symptoms of acute urinary
      tract infection, including bacteriuria.

PMID- 25046619
TI  - Circulating serum miRNA (miR-367-3p, miR-371a-3p, miR-372-3p and miR-373-3p) as
      biomarkers in patients with testicular germ cell cancer.
AB  - PURPOSE: Classic serum tumor markers (human chorionic gonadotropin, alpha1
      fetoprotein and lactate dehydrogenase) have an important role in managing
      testicular germ cell tumor. Since only 60% of all patients with testicular germ
      cell tumor have elevations of these markers, there is a need for new biomarkers
      with greater sensitivity/specificity. miRNAs are deregulated in cancer and could
      serve as noninvasive serum biomarkers. We explored the role of serum miRNAs as a
      novel biomarker in patients with testicular germ cell tumor. MATERIALS AND
      METHODS: Total RNA was isolated from serum. miRNA levels were quantified by
      quantitative real-time polymerase chain reaction. We assessed the miRNAs miR-302a
      3p, 302b-3p, 302c-3p, 367-3p, 371a-3p, 372-3p and 373-3p in a subcohort of 30
      patients with testicular germ cell tumor and 18 healthy subjects. Validation was
      performed in 76 patients treated with inguinal exploration due to suspicion of
      testicular germ cell tumor, of whom 59 had cancer and 17 had benign disease, and
      in 84 healthy male subjects. RESULTS: Serum miR-367-3p, 371a-3p, 372-3p and 373
      3p levels were significantly increased in patients with testicular germ cell
      tumor compared to healthy individuals and patients with nonmalignant testicular
      disease. In particular miR-371a-3p allowed for sensitive (84.7%) and specific
      (99%) identification of patients with testicular germ cell tumor, thus,
      outperforming human chorionic gonadotropin or alpha1-fetoprotein testing.
      Furthermore, miR-367-3p was increased in nonseminoma compared to seminoma cases.
      Serum miRNA levels were increased in patients with advanced local stage and
      metastasis. In 9 patients with localized (clinical stage 1A) testicular germ cell
      tumor serum miR-371a-3p levels decreased postoperatively, indicating tumor
      specific release. CONCLUSIONS: miR-371a-3p allows for better identification of
      testicular germ cell tumor than alpha1-fetoprotein and human chorionic
      gonadotropin. It could be helpful for clinically managing testicular germ cell
      tumor, especially for monitoring surveillance therapy and residual disease after
      chemotherapy.

PMID- 25046620
TI  - DHH is an independent prognosticator of oncologic outcome of clear cell renal
      cell carcinoma.
AB  - PURPOSE: Aberrant HH signaling has proved important in the pathogenesis of
      several solid cancers. Limited in vitro analyses suggested an oncogenic role for
      HH in renal cell carcinoma. In this explorative study we sought to validate
      aberrant HH expression in patients with renal cell carcinoma. MATERIALS AND
      METHODS: A tissue microarray was constructed from 140 radical nephrectomy
      specimens of patients with clear cell renal cell carcinoma. We performed
      immunohistochemistry for Ki67 and HH pathway biomarkers, including PTCH1, Smo,
      SHH, IHH, DHH, Gli1, Gli2 and Gli3. Staining intensity was measured by automated
      image processing and related to tumor stage and grade. The impact of biomarker
      expression on cancer specific survival was determined by univariate and
      multivariate Cox regression analysis. RESULTS: Gli3, PTCH1, DHH and SHH
      demonstrated markedly higher expression in high than in low grade tumors. Tumor
      stage was not associated with marker expression. On univariate analysis DHH
      expression, and tumor grade and stage were associated with cancer specific
      survival. Multivariate analysis revealed that DHH, grade and stage were
      independent predictors of cancer specific survival. CONCLUSIONS: To our knowledge
      we report for the first time that a biomarker of the HH pathway is associated
      with adverse pathological features and poor disease outcomes in patients with
      clear cell renal cell carcinoma. DHH may serve as an independent predictor of
      cancer specific survival in clear cell renal cell carcinoma cases. This supports
      further evaluation of HH signaling to validate the pathway as a target for novel
      therapy.

PMID- 25046621
TI  - Lower urinary tract pain and anterior urethral stricture disease: prevalence and
      effects of urethral reconstruction.
AB  - PURPOSE: Anterior urethral stricture disease most commonly presents as urinary
      obstruction. Lower urinary tract pain is not commonly reported as a presenting
      symptom. We prospectively characterized lower urinary tract pain in association
      with urethral stricture disease and assessed the effects of urethroplasty on this
      pain. MATERIALS AND METHODS: Men (18 years old or older) with anterior urethral
      stricture disease were prospectively enrolled in a longitudinal, multi
      institutional, urethral reconstruction outcomes study from June 2010 to January
      2013 as part of TURNS (Trauma and Urologic Reconstruction Network of Surgeons).
      Preoperative and postoperative lower urinary tract pain was assessed by the
      validated CLSS. Voiding and sexual function was assessed using validated patient
      reported measures, including I-PSS. RESULTS: Preoperatively 118 of 167 men (71%)
      reported urethral pain and 68 (41%) reported bladder pain. Age was the only
      predictor of urethral pain with men 40 years or younger reporting more pain than
      those 60 years old or older (81% vs 58%, p = 0.0104). Lower urinary tract pain
      was associated with worse quality of life and overall voiding symptoms on CLSS
      and I-PSS (each p <0.01). Postoperatively lower urinary tract pain completely
      resolved in 64% of men with urethral pain and in 73.5% with bladder pain. There
      were no predictive factors for changes in lower urinary tract pain after urethral
      reconstruction. CONCLUSIONS: Lower urinary tract pain is common in urethral
      stricture disease, especially in younger men. It is associated with worse quality
      of life and voiding function. In most men lower urinary tract pain resolves after
      urethral reconstruction.

PMID- 25046622
TI  - Bladder instillation of liposome encapsulated onabotulinumtoxina improves
      overactive bladder symptoms: a prospective, multicenter, double-blind, randomized
      trial.
AB  - PURPOSE: Cystoscopic intradetrusor injection of botulinum toxin has helped
      patients with refractory overactive bladder but with the increased risks of
      urinary tract infection and urinary retention. We assessed whether catheter
      instillation of 200 U onabotulinumtoxinA formulated with liposomes is safe and
      effective for the treatment of overactive bladder. MATERIALS AND METHODS: This 2
      center, double-blind, randomized, placebo controlled study enrolled patients with
      overactive bladder inadequately managed with antimuscarinics. Patients were
      assigned to intravesical instillation of lipo-botulinum toxin (31) or normal
      saline (31). The primary end point was the mean change in micturition events per
      3 days at 4 weeks after treatment. Additional end points included mean changes in
      urgency events, frequency and urinary urge incontinence, as well as changes in
      overactive bladder symptom scores and urgency severity scores. RESULTS: At 4
      weeks after treatment lipo-botulinum toxin instillation was associated with a
      statistically significant decrease in micturition events per 3 days (-4.64 for
      lipo-botulinum toxin vs -0.19 for placebo, p = 0.0252). Lipo-botulinum toxin
      instillation was also associated with a statistically significant decrease in
      urinary urgency events with respect to baseline but not placebo. However, lipo
      botulinum toxin instillation was associated with a statistically significant
      decrease in urgency severity scores compared to placebo (p = 0.0181). These
      observed benefits of lipo-botulinum toxin instillation were not accompanied by an
      increased risk of urinary retention. The effects of lipo-botulinum toxin on
      urinary urge incontinence were inconclusive. CONCLUSIONS: A single intravesical
      instillation of lipo-botulinum toxin was associated with decreases in overactive
      bladder symptoms without side effects. Intravesical instillation of liposomal
      botulinum toxin may be a promising approach to treat refractory overactive
      bladder.

PMID- 25046623
TI  - A combination of hemostatic agents may safely replace deep medullary suture
      during laparoscopic partial nephrectomy in a pig model.
AB  - PURPOSE: We assessed whether a combination of the fibrin tissue adhesive
      Tisseel(r) (human fibrinogen and thrombin) plus the hemostatic matrix FloSeal(r)
      (bovine derived gelatin matrix/human thrombin) could safely replace the
      conventional deep medullary suture without compromising outcomes. MATERIALS AND
      METHODS: Laparoscopic mid pole and one-third partial nephrectomy was performed on
      the right kidney of 12 female pigs. The only difference between the 2 groups of 6
      pigs each was the use of a fibrin tissue adhesive plus hemostatic matrix
      combination in group 2 instead of the deep medullary running suture in control
      group 1. Renal scans and angiograms were performed at baseline and before
      sacrifice at 5-week followup. Retrograde in vivo pyelogram was also done.
      RESULTS: No significant difference was seen in operative parameters or
      postoperative course between the groups. Renal scans revealed a statistically
      insignificant trend toward greater uptake loss in group 1 and angiograms showed 3
      major vessel occlusions in that group. No active bleeding was detected. Those 3
      kidneys had significantly poorer postoperative uptake on renal scan than that of
      other kidneys (18.6% vs 39.4%, p = 0.013). Only 1 small asymptomatic
      pseudoaneurysm was noted in group 1. No urine leakage was found in either group.
      No major vessel occlusion, pseudoaneurysm or urinary complications developed in
      group 2. CONCLUSIONS: Even after deep one-third partial nephrectomy FloSeal with
      concurrent Tisseel appeared sufficient to control major medullary vascular
      injuries and replace the deep medullary conventional suture without compromising
      operative outcomes. The potential advantages seen during functional and vascular
      examinations by decreasing the risk of unnecessary segmental vessel occlusion
      need further clinical evaluation.

PMID- 25046624
TI  - Curcumin for the treatment of major depression: a randomised, double-blind,
      placebo controlled study.
AB  - BACKGROUND: Curcumin, the principal curcuminoid derived from the spice turmeric,
      influences several biological mechanisms associated with major depression, namely
      those associated with monoaminergic activity, immune-inflammatory and oxidative
      and nitrosative stress pathways, hypothalamus-pituitary-adrenal (HPA) axis
      activity and neuroprogression. We hypothesised that curcumin would be effective
      for the treatment of depressive symptoms in individuals with major depressive
      disorder. METHODS: In a randomised, double-blind, placebo-controlled study, 56
      individuals with major depressive disorder were treated with curcumin (500 mg
      twice daily) or placebo for 8 weeks. The primary measure was the Inventory of
      Depressive Symptomatology self-rated version (IDS-SR30). Secondary outcomes
      included IDS-SR30 factor scores and the Spielberger State-Trait Anxiety Inventory
      (STAI). RESULTS: From baseline to week 4, both curcumin and placebo were
      associated with improvements in IDS-SR30 total score and most secondary outcome
      measures. From weeks 4 to 8, curcumin was significantly more effective than
      placebo in improving several mood-related symptoms, demonstrated by a significant
      group x time interaction for IDS-SR30 total score (F1, 53=4.22, p=.045) and IDS
      SR30 mood score (F1, 53=6.51, p=.014), and a non-significant trend for STAI trait
      score (F1, 48=2.86, p=.097). Greater efficacy from curcumin treatment was
      identified in a subgroup of individuals with atypical depression. CONCLUSIONS:
      Partial support is provided for the antidepressant effects of curcumin in people
      with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks
      after treatment. LIMITATIONS: Investigations with larger sample sizes, over
      extended treatment periods, and with varying curcumin dosages are required.

PMID- 25046625
TI  - Functional screening of a novel Delta15 fatty acid desaturase from the
      coccolithophorid Emiliania huxleyi.
AB  - The coccolithophorid Emiliania huxleyi is a bloom-forming marine phytoplankton
      thought to play a key role as a biological pump that transfers carbon from the
      surface to the bottom of the ocean, thus contributing to the global carbon cycle.
      This alga is also known to accumulate a variety of polyunsaturated fatty acids.
      At 25 degrees C, E. huxleyi produces mainly 14:0, 18:4n-3, 18:5n-3 and 22:6n-3.
      When the cells were transferred from 25 degrees C to 15 degrees C, the amount of
      unsaturated fatty acids, i.e. 18:1n-9, 18:3n-3 and 18:5n-3, gradually increased.
      Among the predicted desaturase genes whose expression levels were up-regulated at
      low temperature, we identified a gene encoding novel ?15 fatty acid desaturase,
      EhDES15, involved in the production of n-3 polyunsaturated fatty acids in E.
      huxleyi. This desaturase contains a putative transit sequence for localization in
      chloroplasts and a ?6 desaturase-like domain, but it does not contain a
      cytochrome b5 domain nor typical His-boxes found in ?15 desaturases. Heterologous
      expression of EhDES15 cDNA in cyanobacterium Synechocystis sp. PCC 6803 cells
      increased the level of n-3 fatty acid species, which are produced at low levels
      in wild-type cells grown at 30 degrees C. The orthologous genes are only
      conserved in the genomes of prasinophytes and cryptophytes. The His-boxes
      conserved in orthologues varied from that of the canonical ?15 desaturases. These
      results suggested the gene encodes a novel ?15 desaturase responsible for the
      synthesis of 18:3n-3 from 18:2n-6 in E. huxleyi. 

PMID- 25046626
TI  - Microscopy approaches to investigate protein dynamics and lipid organization.
AB  - The structure of cell membranes has been intensively investigated and many models
      and concepts have been proposed for the lateral organization of the plasma
      membrane. While proteomics and lipidomics have identified many if not all
      membrane components, how lipids and proteins interactions are coordinated in a
      specific cell function remains poorly understood. It is generally accepted that
      the organization of the plasma membrane is likely to play a critical role in the
      regulation of cell function such as receptor signalling by governing molecular
      interactions and dynamics. In this review we present different plasma membrane
      models and discuss microscopy approaches used for investigating protein
      behaviour, distribution and lipid organization.

PMID- 25046627
TI  - Effects of acute sleep deprivation on motor and reversal learning in mice.
AB  - Sleep supports the formation of a variety of declarative and non-declarative
      memories, and sleep deprivation often impairs these types of memories. In human
      subjects, natural sleep either during a nap or overnight leads to long-lasting
      improvements in visuomotor and fine motor tasks, but rodent models recapitulating
      these findings have been scarce. Here we present evidence that 5h of acute sleep
      deprivation impairs mouse skilled reach learning compared to a matched period of
      ad libitum sleep. In sleeping mice, the duration of total sleep time during the
      5h of sleep opportunity or during the first bout of sleep did not correlate with
      ultimate gain in motor performance. In addition, we observed that reversal
      learning during the skilled reaching task was also affected by sleep deprivation.
      Consistent with this observation, 5h of sleep deprivation also impaired reversal
      learning in the water-based Y-maze. In conclusion, acute sleep deprivation
      negatively impacts subsequent motor and reversal learning and memory. 

PMID- 25046628
TI  - A method to map changes in bacterial surface composition induced by regulatory
      RNAs in Escherichia coli and Staphylococcus aureus.
AB  - We have adapted a method to map cell surface proteins and to monitor the effect
      of specific regulatory RNAs on the surface composition of the bacteria. This
      method involves direct labeling of surface proteins of living bacteria using
      fluorescent dyes and a subsequent separation of the crude extract by 2D gel
      electrophoresis. The strategy yields a substantial enrichment in surface proteins
      over cytoplasmic proteins. We validated this method by monitoring the effect of
      the regulatory RNA MicA in Escherichia coli, which regulates the synthesis of
      several outer membrane proteins, and highlighted the role of Staphylococcus
      aureus RNAIII for the maintenance of cell wall integrity. 

PMID- 25046629
TI  - Fibrin(ogen)olytic and platelet modulating activity of a novel protease from the
      Echis multisquamatis snake venom.
AB  - The variety of enzymes including serine proteases that possess fibrin(ogen)olytic
      and platelet modulating activity have been discovered in different snake venoms.
      In our work the fibrin(ogen)olytic and platelet modulating activity of a new
      protease from Echis multisquamatis snake venom was studied. It was shown that
      purified enzyme cleaved the VbetaR42-A43 bond of fibrinogen during first contact
      with the substrate following much slower hydrolysis of C-terminus of fibrinogen
      Aalpha-chain. Protease hydrolysed fibrin clot too, but at much slower rate and
      cleaved both C-terminus of Aalpha-chain and VbetaR42-A43 bond of Bbeta-chain
      simultaneously. Preincubation of fibrinogen with protease dramatically elongated
      thrombin clotting time and the clot formed from a mixture of native fibrinogen
      and fibrinogen desVbeta(1-42)2 digested by plasmin much faster than a native
      fibrin clot. The protease did not activate platelets nor cause changes in their
      shape and granularity, but it reduced platelets aggregation induced by ADP. 

PMID- 25046630
TI  - The impact of out-of-pocket payments on health care inequity: the case of
      national health insurance in South Korea.
AB  - The global financial crisis of 2008 has led to the reinforcement of patient cost
      sharing in health care policy. This study aimed to explore the impact of direct
      out-of pocket payments (OOPs) on health care utilization and the resulting
      financial burden across income groups under the South Korean National Health
      Insurance (NHI) program with universal population coverage. We used the fourth
      Korean National Health and Nutrition Examination Survey (KNHNES-IV) and the
      Korean Household Income and Expenditure Survey (KHIES) of 2007, 2008 and 2009.
      The Horizontal Inequity Index (HIwv) and the average unit OOPs were used to
      measure income-related inequity in the quantitative and qualitative aspects of
      health care utilization, respectively. For financial burden, the incidence rates
      of catastrophic health expenditure (CHE) were compared across income groups. For
      outpatient and hospital visits, there was neither pro-poor or pro-rich
      inequality. The average unit OOPs of the poorest quintile was approximately 75%
      and 60% of each counterpart in the richest quintile in the outpatient and
      inpatient services. For the CHE threshold of 40%, the incidence rates were 5.7%,
      1.67%, 0.72%, 0.33% and 0.27% in quintiles I (the poorest quintile), II, III, IV
      and V, respectively. Substantial OOPs under the NHI are disadvantageous,
      particularly for the lowest income group in terms of health care quality and
      financial burden. 

PMID- 25046631
TI  - Differences of urinary arsenic metabolites and methylation capacity between
      individuals with and without skin lesions in Inner Mongolia, Northern China.
AB  - Incomplete arsenic (As) methylation has been considered a risk factor of As
      related diseases. This study aimed to examine the difference of urinary As
      metabolites and the methylation capacity between subjects with and without skin
      lesions. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and
      dimethylarsinic acid (DMA) were analyzed. The percentage of each As species
      (iAs%, MMA%, and DMA%), the primary methylation index (PMI) and secondary
      methylation index (SMI) were calculated. The results showed that subjects with
      skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 MUg/g Cr, p =
      0.006) and MMA (69.34 vs. 42.85 MUg/g Cr, p = 0.016) than subjects without skin
      lesions after adjustment for several confounders. Significant differences of
      urianry MMA% (15.49 vs. 12.11, p = 0.036) and SMI (0.74 vs. 0.81, p = 0.025) were
      found between the two groups. The findings of the present study suggest that
      subjects with skin lesions may have a lower As methylation capacity than subjects
      without skin lesions. 

PMID- 25046632
TI  - Comparison and cost analysis of drinking water quality monitoring requirements
      versus practice in seven developing countries.
AB  - Drinking water quality monitoring programs aim to support provision of safe
      drinking water by informing water quality management. Little evidence or guidance
      exists on best monitoring practices for low resource settings. Lack of financial,
      human, and technological resources reduce a country's ability to monitor water
      supply. Monitoring activities were characterized in Cambodia, Colombia, India
      (three states), Jordan, Peru, South Africa, and Uganda according to water sector
      responsibilities, monitoring approaches, and marginal cost. The seven study
      countries were selected to represent a range of low resource settings. The focus
      was on monitoring of microbiological parameters, such as E. coli, coliforms, and
      H2S-producing microorganisms. Data collection involved qualitative and
      quantitative methods. Across seven study countries, few distinct approaches to
      monitoring were observed, and in all but one country all monitoring relied on
      fixed laboratories for sample analysis. Compliance with monitoring requirements
      was highest for operational monitoring of large water supplies in urban areas.
      Sample transport and labor for sample collection and analysis together constitute
      approximately 75% of marginal costs, which exclude capital costs. There is
      potential for substantive optimization of monitoring programs by considering
      field-based testing and by fundamentally reconsidering monitoring approaches for
      non-piped supplies. This is the first study to look quantitatively at water
      quality monitoring practices in multiple developing countries. 

PMID- 25046633
TI  - Climate change and human health.

PMID- 25046634
TI  - A decision support system for drinking water production integrating health risks
      assessment.
AB  - The issue of drinking water quality compliance in small and medium scale water
      services is of paramount importance in relation to the 98/83/CE European Drinking
      Water Directive (DWD). Additionally, concerns are being expressed over the
      implementation of the DWD with respect to possible impacts on water quality from
      forecast changes in European climate with global warming and further anticipated
      reductions in north European acid emissions. Consequently, we have developed a
      decision support system (DSS) named ARTEM-WQ (AwaReness Tool for the Evaluation
      and Mitigation of drinking Water Quality issues resulting from environmental
      changes) to support decision making by small and medium plant operators and other
      water stakeholders. ARTEM-WQ is based on a sequential risk analysis approach that
      includes consideration of catchment characteristics, climatic conditions and
      treatment operations. It provides a holistic evaluation of the water system,
      while also assessing human health risks of organic contaminants potentially
      present in treated waters (steroids, pharmaceuticals, pesticides, bisphenol-a,
      polychlorobiphenyls, polycyclic aromatic hydrocarbons, petrochemical hydrocarbons
      and disinfection by-products; n = 109). Moreover, the system provides
      recommendations for improvement while supporting decision making in its widest
      context. The tool has been tested on various European catchments and shows a
      promising potential to inform water managers of risks and appropriate mitigative
      actions. Further improvements should include toxicological knowledge advancement,
      environmental background pollutant concentrations and the assessment of the
      impact of distribution systems on water quality variation. 

PMID- 25046635
TI  - Associations between perceptions of drinking water service delivery and measured
      drinking water quality in rural Alabama.
AB  - Although small, rural water supplies may present elevated microbial risks to
      consumers in some settings, characterizing exposures through representative point
      of-consumption sampling is logistically challenging. In order to evaluate the
      usefulness of consumer self-reported data in predicting measured water quality
      and risk factors for contamination, we compared matched consumer interview data
      with point-of-survey, household water quality and pressure data for 910
      households served by 14 small water systems in rural Alabama. Participating
      households completed one survey that included detailed feedback on two key areas
      of water service conditions: delivery conditions (intermittent service and low
      water pressure) and general aesthetic characteristics (taste, odor and color),
      providing five condition values. Microbial water samples were taken at the point
      of-use (from kitchen faucets) and as-delivered from the distribution network
      (from outside flame-sterilized taps, if available), where pressure was also
      measured. Water samples were analyzed for free and total chlorine, pH, turbidity,
      and presence of total coliforms and Escherichia coli. Of the 910 households
      surveyed, 35% of participants reported experiencing low water pressure, 15%
      reported intermittent service, and almost 20% reported aesthetic problems (taste,
      odor or color). Consumer-reported low pressure was associated with lower gauge
      measured pressure at taps. While total coliforms (TC) were detected in 17% of
      outside tap samples and 12% of samples from kitchen faucets, no reported water
      service conditions or aesthetic characteristics were associated with presence of
      TC. We conclude that consumer-reported data were of limited utility in predicting
      potential microbial risks associated with small water supplies in this setting,
      although consumer feedback on low pressure-a risk factor for contamination-may be
      relatively reliable and therefore useful in future monitoring efforts. 

PMID- 25046636
TI  - Detection of Legionella, L. pneumophila and Mycobacterium avium complex (MAC)
      along potable water distribution pipelines.
AB  - Inhalation of potable water presents a potential route of exposure to
      opportunistic pathogens and hence warrants significant public health concern.
      This study used qPCR to detect opportunistic pathogens Legionella spp., L.
      pneumophila and MAC at multiple points along two potable water distribution
      pipelines. One used chlorine disinfection and the other chloramine disinfection.
      Samples were collected four times over the year to provide seasonal variation and
      the chlorine or chloramine residual was measured during collection. Legionella
      spp., L. pneumophila and MAC were detected in both distribution systems
      throughout the year and were all detected at a maximum concentration of 103
      copies/mL in the chlorine disinfected system and 106, 103 and 104 copies/mL
      respectively in the chloramine disinfected system. The concentrations of these
      opportunistic pathogens were primarily controlled throughout the distribution
      network through the maintenance of disinfection residuals. At a dead-end and when
      the disinfection residual was not maintained significant (p < 0.05) increases in
      concentration were observed when compared to the concentration measured closest
      to the processing plant in the same pipeline and sampling period. Total coliforms
      were not present in any water sample collected. This study demonstrates the
      ability of Legionella spp., L. pneumophila and MAC to survive the potable water
      disinfection process and highlights the need for greater measures to control
      these organisms along the distribution pipeline and at point of use. 

PMID- 25046637
TI  - Synthetic biodegradable hydrogel delivery of demineralized bone matrix for bone
      augmentation in a rat model.
AB  - There exists a strong clinical need for a more capable and robust method to
      achieve bone augmentation, and a system with fine-tuned delivery of demineralized
      bone matrix (DBM) has the potential to meet that need. As such, the objective of
      the present study was to investigate a synthetic biodegradable hydrogel for the
      delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol)
      fumarate) (OPF) constructs were designed and fabricated by varying the content of
      rat-derived DBM particles (either 1:3, 1:1 or 3:1 DBM:OPF weight ratio on a dry
      basis) and using two DBM particle size ranges (50-150 or 150-250 MUm). The
      physical properties of the constructs and the bioactivity of the DBM were
      evaluated. Selected formulations (1:1 and 3:1 with 50-150 MUm DBM) were evaluated
      in vivo compared to an empty control to investigate the effect of DBM dose and
      construct properties on bone augmentation. Overall, 3:1 constructs with higher
      DBM content achieved the greatest volume of bone augmentation, exceeding 1:1
      constructs and empty implants by 3- and 5-fold, respectively. As such, we have
      established that a synthetic, biodegradable hydrogel can function as a carrier
      for DBM, and that the volume of bone augmentation achieved by the constructs
      correlates directly to the DBM dose.

PMID- 25046639
TI  - Identification of protein interaction partners in mammalian cells using SILAC
      immunoprecipitation quantitative proteomics.
AB  - Quantitative proteomics combined with immuno-affinity purification, SILAC
      immunoprecipitation, represent a powerful means for the discovery of novel
      protein:protein interactions. By allowing the accurate relative quantification of
      protein abundance in both control and test samples, true interactions may be
      easily distinguished from experimental contaminants. Low affinity interactions
      can be preserved through the use of less-stringent buffer conditions and remain
      readily identifiable. This protocol discusses the labeling of tissue culture
      cells with stable isotope labeled amino acids, transfection and
      immunoprecipitation of an affinity tagged protein of interest, followed by the
      preparation for submission to a mass spectrometry facility. This protocol then
      discusses how to analyze and interpret the data returned from the mass
      spectrometer in order to identify cellular partners interacting with a protein of
      interest. As an example this technique is applied to identify proteins binding to
      the eukaryotic translation initiation factors: eIF4AI and eIF4AII. 

PMID- 25046638
TI  - In vitro systems toxicology approach to investigate the effects of repeated
      cigarette smoke exposure on human buccal and gingival organotypic epithelial
      tissue cultures.
AB  - Smoking has been associated with diseases of the lung, pulmonary airways and oral
      cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate
      with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration
      of smoking-related gene expression changes in oral epithelial cells is similar to
      that in bronchial and nasal epithelial cells. Using a systems toxicology
      approach, we have previously assessed the impact of cigarette smoke (CS) seen as
      perturbations of biological processes in human nasal and bronchial organotypic
      epithelial culture models. Here, we report our further assessment using in vitro
      human oral organotypic epithelium models. We exposed the buccal and gingival
      organotypic epithelial tissue cultures to CS at the air-liquid interface. CS
      exposure was associated with increased secretion of inflammatory mediators,
      induction of cytochrome P450s activity and overall weak toxicity in both tissues.
      Using microarray technology, gene-set analysis and a novel computational modeling
      approach leveraging causal biological network models, we identified CS impact on
      xenobiotic metabolism-related pathways accompanied by a more subtle alteration in
      inflammatory processes. Gene-set analysis further indicated that the CS-induced
      pathways in the in vitro buccal tissue models resembled those in the in vivo
      buccal biopsies of smokers from a published dataset. These findings support the
      translatability of systems responses from in vitro to in vivo and demonstrate the
      applicability of oral organotypical tissue models for an impact assessment of CS
      on various tissues exposed during smoking, as well as for impact assessment of
      reduced-risk products.

PMID- 25046640
TI  - Collagen microgel-assisted dexamethasone release from PLLA-collagen hybrid
      scaffolds of controlled pore structure for osteogenic differentiation of
      mesenchymal stem cells.
AB  - Directed stem cell differentiation over three-dimensional porous scaffolds
      capable of releasing bioactive instructive cues is an important tool in tissue
      engineering. In this research, we have prepared dexamethasone (Dex)-releasing
      collagen microbead-functionalized poly(L-Lactide)-collagen hybrid scaffolds as an
      osteoinductive platform for human bone marrow-derived mesenchymal stem cells
      (MSCs). The scaffolds were prepared by a combined method of emulsion freeze
      drying and porogen-leaching using pre-prepared ice collagen particulates as a
      porogen material. Dex release from the hybrid scaffolds was studied at 37 
      degrees C under shaking condition and the impact of released Dex towards
      osteogenic lineage differentiation was investigated by 3 week in vitro culture of
      MSCs. The results showed that hybrid scaffolds had controlled pore structure and
      interconnected pores deposited with collagen fibers. The hybrid scaffold
      facilitated cell seeding and the spatial localization of Dex/collagen microbeads
      facilitated a microgel-assisted spatio-temporal control of Dex release. The
      released Dex was useful for osteogenic differentiation of MSCs, which was
      confirmed from the elevated expression of osteogenic-specific gene-encoded
      proteins. The hybrid scaffolds should be useful for regeneration of a functional
      bone tissue. 

PMID- 25046641
TI  - Functional photobiomodulation.

PMID- 25046646
TI  - 3D optical printing of piezoelectric nanoparticle-polymer composite materials.
AB  - Here we demonstrate that efficient piezoelectric nanoparticle-polymer composite
      materials can be optically printed into three-dimensional (3D) microstructures
      using digital projection printing. Piezoelectric polymers were fabricated by
      incorporating barium titanate (BaTiO3, BTO) nanoparticles into photoliable
      polymer solutions such as polyethylene glycol diacrylate and exposing to digital
      optical masks that could be dynamically altered to generate user-defined 3D
      microstructures. To enhance the mechanical-to-electrical conversion efficiency of
      the composites, the BTO nanoparticles were chemically modified with acrylate
      surface groups, which formed direct covalent linkages with the polymer matrix
      under light exposure. The composites with a 10% mass loading of the chemically
      modified BTO nanoparticles showed piezoelectric coefficients (d(33)) of ~ 40
      pC/N, which were over 10 times larger than composites synthesized with unmodified
      BTO nanoparticles and over 2 times larger than composites containing unmodified
      BTO nanoparticles and carbon nanotubes to boost mechanical stress transfer
      efficiencies. These results not only provide a tool for fabricating 3D
      piezoelectric polymers but lay the groundwork for creating highly efficient
      piezoelectric polymer materials via nanointerfacial tuning.

PMID- 25046647
TI  - Markers of inflammation and oxidative stress studied in adjuvant-induced
      arthritis in the rat on systemic and local level affected by pinosylvin and
      methotrexate and their combination.
AB  - Oxidative stress (OS) is important in the pathogenesis of autoimmune diseases
      such as rheumatoid arthritis (RA) and its experimental model--adjuvant arthritis
      (AA). Antioxidants are scarcely studied in autoimmunity, and future analyses are
      needed to assess its effects in ameliorating these diseases. Although there are
      studies about antioxidants effects on the course of RA, their role in combination
      therapy has not yet been studied in detail, especially on extra-articular
      manifestations of AA. During the 28-d administration of pinosylvin (PIN) in
      monotherapy and in combination with methotrexate (MTX) to AA rats, we evaluated
      the impact of the treatment on selected parameters. The experiment included:
      healthy controls, untreated AA, AA administered 50 mg/kg b.w. of PIN daily p.o.,
      AA administered 0.4 mg/kg b.w. of MTX twice weekly p.o. and AA treated with a
      combination of PIN+MTX. AA was monitored using: hind paw volume, C-reactive
      protein, monocyte chemotactic protein-1 (MCP-1), thiobarbituric acid reactive
      substances (TBARS) and F2-isoprostanes in plasma, gamma-glutamyltransferase
      activity in spleen, activity of lipoxygenase (LOX) in lung, heme oxygenase-1 (HO
      1) and nuclear factor kappa B (NF-kappaB) in liver and lung. PIN monotherapy
      significantly improved the activation of NF-kappaB in liver and lung, HO-1
      expression and activity of LOX in the lung, MCP-1 levels in plasma (on 14th d)
      and plasmatic levels of F2-isoprostanes. An important contribution of PIN to MTX
      effect was the reduction of OS (an increase of HO-1 expression in lung and
      reduction of plasmatic TBARS) and decrease of LOX activity in the lung.

PMID- 25046648
TI  - Predictive genetic testing for adult-onset disorders in minors: a critical
      analysis of the arguments for and against the 2013 ACMG guidelines.
AB  - The publication of the ACMG recommendations has reignited the debate over
      predictive testing for adult-onset disorders in minors. Response has been
      polarized. With this in mind, we review and critically analyze this debate.
      First, we identify long-standing inconsistencies between consensus guidelines and
      clinical practice regarding risk assessment for adult-onset genetic disorders in
      children using family history and molecular analysis. Second, we discuss the
      disparate assumptions regarding the nature of whole genome and exome sequencing
      underlying arguments of both supporters and critics, and the role these
      assumptions play in the arguments for and against reporting. Third, we suggest
      that implicit differences regarding the definition of best interests of the child
      underlie disparate conclusions as to the best interests of children in this
      context. We conclude by calling for clarity and consensus concerning the central
      foci of this debate. 

PMID- 25046649
TI  - Alternative quality assessment strategy to compare performances of GPCR-ligand
      docking protocols: the human adenosine A(2A) receptor as a case study.
AB  - The progress made in the field of G protein-coupled receptors (GPCRs) structural
      determination has increased the adoption of docking-driven approaches for the
      identification or optimization of novel potent and selective ligands. In this
      work, we compared the performances of the 16 different docking/scoring
      combinations using the recently released crystal structures of the human A2A AR
      (hA2A AR) in complex with both agonists and antagonists. The proposed evaluation
      strategy encompasses the use of three complementary "quality descriptors": (a)
      the number of conformations generated by a docking algorithm having a RMSD value
      lower than the crystal structure resolution (R); (b) a novel consensus-based
      function defined as "protocol score"; and (c) the interaction energy maps (IEMs)
      analysis, based on the identification of key ligand-receptor interactions
      observed in the crystal structures. 

PMID- 25046650
TI  - The Multiple Sclerosis Performance Test (MSPT): an iPad-based disability
      assessment tool.
AB  - Precise measurement of neurological and neuropsychological impairment and
      disability in multiple sclerosis is challenging. We report a new test, the
      Multiple Sclerosis Performance Test (MSPT), which represents a new approach to
      quantifying MS related disability. The MSPT takes advantage of advances in
      computer technology, information technology, biomechanics, and clinical
      measurement science. The resulting MSPT represents a computer-based platform for
      precise, valid measurement of MS severity. Based on, but extending the Multiple
      Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative
      data on walking speed, balance, manual dexterity, visual function, and cognitive
      processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls
      (HC). MSPT scores were highly reproducible, correlated strongly with technician
      administered test scores, discriminated MS from HC and severe from mild MS, and
      correlated with patient reported outcomes. Measures of reliability, sensitivity,
      and clinical meaning for MSPT scores were favorable compared with technician
      based testing. The MSPT is a potentially transformative approach for collecting
      MS disability outcome data for patient care and research. Because the testing is
      computer-based, test performance can be analyzed in traditional or novel ways and
      data can be directly entered into research or clinical databases. The MSPT could
      be widely disseminated to clinicians in practice settings who are not connected
      to clinical trial performance sites or who are practicing in rural settings,
      drastically improving access to clinical trials for clinicians and patients. The
      MSPT could be adapted to out of clinic settings, like the patient's home, thereby
      providing more meaningful real world data. The MSPT represents a new paradigm for
      neuroperformance testing. This method could have the same transformative effect
      on clinical care and research in MS as standardized computer-adapted testing has
      had in the education field, with clear potential to accelerate progress in
      clinical care and research.

PMID- 25046651
TI  - Magnetic effect on the interfacial energy of the Ni(1 1 1)/Cr(1 1 0) interface.
AB  - The work of separation and interfacial energy of the Ni(1 1 1)/Cr(1 1 0)
      interface are calculated via first-principles methods. Both coherent and
      semicoherent interfaces are considered. We find that magnetism has a significant
      effect on the interfacial energy, i.e. removing magnetism decreases the
      interfacial energy of the semicoherent interface by around 50% . Electronic,
      magnetic and atomic structures at the interface are discussed. An averaging
      scheme is used to estimate the work of separation and interfacial energy of
      semicoherent interfaces based on the results of coherent interfaces. The
      limitations of the scheme are discussed.

PMID- 25046652
TI  - Using [1-(13) C]lactic acid for hyperpolarized (13) C MR cardiac studies.
AB  - PURPOSE: Hyperpolarized [1-(13) C]lactate in solution may be a clinically
      relevant and safe substrate for real time MR investigations of key metabolic
      pathways. The potential of using hyperpolarized [1-(13) C]lactate for magnetic
      resonance studies of cardiac metabolism in vivo was explored. METHODS: Neat [1
      (13) C]lactic acid was hyperpolarized using the dynamic nuclear polarization
      process. Cardiac MR spectroscopy experiments were performed in vivo using
      hyperpolarized [1-(13) C]lactate and [1-(13) C]pyruvate in solutions. RESULTS: A
      high degree of polarization was achieved for [1-(13) C]lactate in solution
      (16.7%). (13) C-bicarbonate was observed in rat hearts in vivo after either
      hyperpolarized [1-(13) C]lactate or hyperpolarized [1-(13) C]pyruvate was
      infused, but lower (13) C-bicarbonate to substrate ratio was observed with
      hyperpolarized [1-(13) C]lactate infusions. The response of (13) C-bicarbonate
      signal as a function of hyperpolarized [1-(13) C]lactate doses was also
      investigated and a saturation of (13) C-bicarbonate signal was observed at the
      highest dose of [1-(13) C]lactate used (0.69 mmol/kg). CONCLUSION: This study
      demonstrated that the use of neat [1-(13) C]lactic acid as the DNP sample is a
      potential alternative to [1-(13) C]pyruvic acid for cardiac hyperpolarized (13) C
      MR studies. Hyperpolarized [1-(13) C]lactate may enable noninvasive assessment of
      cardiac PDH flux in cardiac patients in the near future.

PMID- 25046653
TI  - Verification of an immunoturbidimetric assay for heart-type fatty acid-binding
      protein (H-FABP) on a clinical chemistry platform and establishment of the upper
      reference limit.
AB  - BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is an early biomarker
      of cardiac injury. Randox Laboratories developed an immunoturbidimetric H-FABP
      assay for non-proprietary automated clinical chemistry analysers that could be
      useful in the emergency department. We verified the analytical performances
      claimed by Randox Laboratories on Roche Cobas 6000 clinical chemistry platform in
      use in our laboratory, and we defined our own 99th percentile upper reference
      limit for H-FABP. METHODS: For the verification of method performances, we used
      pools of spared patient samples from routine and two levels of quality control
      material, while samples for the reference value study were collected from 545
      blood donors. Following CLSI guidelines we verified limit of blank (LOB), limit
      of detection (LOD), limit of quantitation (LOQ), repeatability and within
      laboratory precision, trueness, linearity, and the stability of H-FABP in EDTA
      over 24h. RESULTS AND DISCUSSION: The LOQ (3.19 MUg/L) was verified with a CV% of
      10.4. The precision was verified for the low (mean 5.88 MUg/L, CV=6.7%), the
      medium (mean 45.28 MUg/L, CV=3.0%), and the high concentration (mean 88.81 MUg/L,
      CV=4.0%). The trueness was verified as well as the linearity over the indicated
      measurement interval of 0.747-120 MUg/L. The H-FABP in EDTA samples is stable
      throughout 24h both at room temperature and at 4  degrees C. The H-FABP 99th
      percentile upper reference limit for all subjects (3.60 MUg/L, 95% CI 3.51-3.77)
      is more appropriate than gender-specific ones that are not statistically
      different.

PMID- 25046654
TI  - The association of inflammatory markers with cerebral vasoreactivity and carotid
      atherosclerosis in transient ischaemic attack.
AB  - OBJECTIVES: Inflammatory mediators have an important role in the pathogenesis of
      stroke. Increased activity of inflammatory mediators initiates the development of
      atherosclerosis independently of other risk factors, thus compromising brain
      microcirculation and causing transient ischaemic attack (TIA). The aim of our
      study was to evaluate the relationship between serum level of cellular adhesion
      molecules (ICAM-1), interleukin-6 (IL-6) and C-reactive protein (CRP) with
      carotid intima-media thickness (IMT) and breath-holding index (BHI) in subjects
      with transient ischaemic attack. We also aimed to assess the difference of those
      markers between TIA patients and disease-free control individuals. DESIGN AND
      METHODS: The study included 45 TIA patients and 36 disease-free controls matched
      for age, gender and vascular risk profile. The degree of carotid atherosclerosis
      was assessed by colour Doppler with measurements of carotid IMT. Transcranial
      Doppler (TCD) ultrasound was performed in order to assess BHI. IMT, TCD, BHI and
      serum concentrations of ICAM-1, IL-6, and CRP were measured for all study
      subjects. RESULTS: Inflammatory markers IL-6, ICAM-1 and CRP were significantly
      higher in TIA patients than in disease-free controls (P<0.001, P=0.026, P<0.001,
      respectively). TIA patients had significantly lower values of BHI and higher IMT
      relative to disease-free control individuals (P<0.001). CONCLUSIONS: TIA is
      associated with higher ICAM-1, IL-6 and CRP, pointing to the marked inflammatory
      response to cerebral ischaemia. Inflammatory markers are associated with higher
      IMT and lower BHI, indicating the insufficient cerebral perfusion due to the
      underlying atherosclerotic disease. Our findings highlight the key significance
      of inflammation in the early response to ischaemia during the transitory
      ischaemic episode.

PMID- 25046655
TI  - Skin equivalent tensional force alters keloid fibroblast behavior and phenotype.
AB  - Skin tension may influence keloid scar behavior, development, and spreading,
      e.g., butterfly-shaped keloid disease in the sternum. Here, we developed a three
      dimensional (3D) in vitro model to mimic in vivo tension and evaluate keloid
      fibroblast (KF) behavior and extracellular matrix synthesis under tension. In
      vivo skin tension measured in volunteers (n = 4) using 3D image photogrammetry
      enabled prediction of actual force (35 mN). A novel cell force monitor applied
      tension in a fibroblast-populated 3D collagen lattice replicating the in vivo
      force. The effect of tension on keloid (n = 10) fibroblast (KF) and normal skin
      (n = 10) fibroblasts (NF) at set time points (6, 12, and 24 hours) was measured
      in Hsp27, PAI-2, and alpha2beta1 integrin, tension-related genes demonstrating
      significant (p < 0.05) time-dependent regulation of these genes in NF vs. KF with
      and without tension. KF showed higher (p < 0.05) proliferation post-tension.
      Knockdown of all three genes in 24 and 48 hours with and without tension showed
      significant down-regulation in NF vs. KF. Additionally, we show significant (p <
      0.05) modification of the expression of extracellular matrix-related genes post
      tension following down-regulation of Hsp27, PAI-2, or alpha2beta1 integrin.
      Finally, we demonstrate significant alteration in NF compared with KF morphology
      following knockdown. In conclusion, this study shows induction of tension-related
      genes expression following mechano-regulation in KFs, with potential relevance to
      its development and therapy. 

PMID- 25046657
TI  - Microdynamics mechanism of thermal-induced hydrogel network destruction of
      poly(vinyl alcohol) in D2O studied by two-dimensional infrared correlation
      spectroscopy.
AB  - Microdynamics mechanism of thermal-induced hydrogel network destruction of
      poly(vinyl alcohol) (PVA) in D2O at heating (25-62  degrees C) was studied by in
      situ Fourier transform infrared (FTIR) spectroscopy combining with moving-window
      two-dimensional (MW2D) technique and two-dimensional (2D) correlation analysis.
      The temperature range of hydrogel destruction was determined within 34-52 
      degrees C by dynamic rheological test at first, and then also monitored by MW2D
      FTIR spectra. The motion of vs(-C-O-, microcrystals) was important in the entire
      hydrogel destruction process. The microdynamics mechanism of PVA molecular chains
      can be elaborated as follows: At 32  degrees C, the number of D2O molecules in
      the swollen amorphous remains unchanged. At 32-37  degrees C, more D2O molecules
      enter into the swollen amorphous region, and the groups of -C-O-, together with 
      CH2-, are partially hydrated. At 37  degrees C, the intramolecular or
      intermolecular hydrogen bonds of PVA are dissociated. The physical cross-linking
      points of hydrogel are broken due to the melting of PVA microcrystals. At 42 
      degrees C, the dissociated hydroxyls from PVA microcrystals rapidly integrate
      solid hydrogen bonds with D2O molecules. The groups of -C-O- and -CH- are
      completely hydrated by D2O simultaneously. At 45-55  degrees C, PVA molecules are
      surrounded by more D2O molecules. The partially hydrated -CH2- is completely
      hydrated, and all of the PVA molecules are fully dissolved in D2O. 

PMID- 25046656
TI  - Sex differences in the effort indicators during cardiopulmonary resuscitation
      manoeuvres on manikins.
AB  - The aims of this study were to examine sex differences in college students while
      they performed cardiopulmonary resuscitation (CPR) on a manikin for 20 min in (a)
      objective and subjective effort indicators and (b) to analyse the influence of
      potential confounders (age, BMI and cardiorespiratory fitness) on these sex
      differences. Sixty-three participants were recruited. Participants performed 20
      min of CPR on a manikin. During the CPR trial, percentages of maximal heart rate
      levels were higher in women than in men (P<0.05) and perceived exertion increased
      significantly in both sexes over time (P=0.05); furthermore, at the last two time
      points analysed, women scored higher than men (P<0.05). However, these sex
      differences disappeared when controlling for age, BMI and cardiorespiratory
      fitness. In conclusion, indicators of exertion during CPR are higher in women
      than in men, but these sex differences are because of BMI and differences in
      physical fitness conditions. 

PMID- 25046658
TI  - Competition between molecular adsorption and diffusion: dramatic consequences for
      SERS in colloidal solutions.
AB  - This study highlights a crucial but often overlooked consideration during sample
      preparation involving surface-adsorbing species: the competition between analyte
      adsorption and analyte diffusion/mixing strongly affects the distribution of
      analytes throughout the sample. In cases of fast analyte adsorption, we argue
      that the use of large-dilution factors, a common approach for sample preparation
      in surface-enhanced Raman spectroscopy (SERS), may result in an extreme
      nonuniformity of the surface coverage. This has a direct effect on the
      aggregation state of the colloidal solution and therefore on the overall SERS
      signal. Explicitly, we show that the average SERS signal obtained from typical
      dyes in colloidal solutions can be drastically different for two seemingly
      equivalent samples, differing only in the method by which the dye molecules were
      diluted. We, in addition, discuss the implications of such nonuniformity on the
      statistics of SERS intensities in the context of single-molecule detection. These
      results vividly highlight the importance of the dilution step in any experiments
      involving surface-adsorbing species and position SERS as an ideal tool to
      evidence such effects. In such cases, a simple half-half dilution procedure
      should be adopted as the standard method to mitigate these effects. 

PMID- 25046659
TI  - Super-resolution imaging of neuronal dense-core vesicles.
AB  - Detection of fluorescence provides the foundation for many widely utilized and
      rapidly advancing microscopy techniques employed in modern biological and medical
      applications. Strengths of fluorescence include its sensitivity, specificity, and
      compatibility with live imaging. Unfortunately, conventional forms of
      fluorescence microscopy suffer from one major weakness, diffraction-limited
      resolution in the imaging plane, which hampers studies of structures with
      dimensions smaller than ~250 nm. Recently, this limitation has been overcome with
      the introduction of super-resolution fluorescence microscopy techniques, such as
      photoactivated localization microscopy (PALM). Unlike its conventional
      counterparts, PALM can produce images with a lateral resolution of tens of
      nanometers. It is thus now possible to use fluorescence, with its myriad
      strengths, to elucidate a spectrum of previously inaccessible attributes of
      cellular structure and organization. Unfortunately, PALM is not trivial to
      implement, and successful strategies often must be tailored to the type of system
      under study. In this article, we show how to implement single-color PALM studies
      of vesicular structures in fixed, cultured neurons. PALM is ideally suited to the
      study of vesicles, which have dimensions that typically range from ~50-250 nm.
      Key steps in our approach include labeling neurons with photoconvertible (green
      to red) chimeras of vesicle cargo, collecting sparsely sampled raw images with a
      super-resolution microscopy system, and processing the raw images to produce a
      high-resolution PALM image. We also demonstrate the efficacy of our approach by
      presenting exceptionally well-resolved images of dense-core vesicles (DCVs) in
      cultured hippocampal neurons, which refute the hypothesis that extrasynaptic
      trafficking of DCVs is mediated largely by DCV clusters. 

PMID- 25046660
TI  - Human natural killer cells promote cross-presentation of tumor cell-derived
      antigens by dendritic cells.
AB  - Dendritic cells (DCs) cross-present antigen (Ag) to initiate T-cell immunity
      against most infections and tumors. Natural killer (NK) cells are innate
      cytolytic lymphocytes that have emerged as key modulators of multiple DC
      functions. Here, we show that human NK cells promote cross-presentation of tumor
      cell-derived Ag by DC leading to Ag-specific CD8(+) T-cell activation.
      Surprisingly, cytotoxic function of NK cells was not required. Instead, we
      highlight a critical and nonredundant role for IFN-gamma and TNF-alpha production
      by NK cells to enhance cross-presentation by DC using two different Ag models.
      Importantly, we observed that NK cells promote cell-associated Ag cross
      presentation selectively by monocytes-derived DC (Mo-DC) and CD34-derived
      CD11b(neg) CD141(high) DC subsets but not by myeloid CD11b(+) DC. Moreover, we
      demonstrate that triggering NK cell activation by monoclonal antibodies (mAbs)
      coated tumor cells leads to efficient DC cross-presentation, supporting the
      concept that NK cells can contribute to therapeutic mAbs efficiency by inducing
      downstream adaptive immunity. Taken together, our findings point toward a novel
      role of human NK cells bridging innate and adaptive immunity through selective
      induction of cell-associated Ag cross-presentation by CD141(high) DC, a process
      that could be exploited to better harness Ag-specific cellular immunity in
      immunotherapy. 

PMID- 25046661
TI  - Voluntary breath-hold technique for reducing heart dose in left breast
      radiotherapy.
AB  - Breath-holding techniques reduce the amount of radiation received by cardiac
      structures during tangential-field left breast radiotherapy. With these
      techniques, patients hold their breath while radiotherapy is delivered, pushing
      the heart down and away from the radiotherapy field. Despite clear dosimetric
      benefits, these techniques are not yet in widespread use. One reason for this is
      that commercially available solutions require specialist equipment, necessitating
      not only significant capital investment, but often also incurring ongoing costs
      such as a need for daily disposable mouthpieces. The voluntary breath-hold
      technique described here does not require any additional specialist equipment.
      All breath-holding techniques require a surrogate to monitor breath-hold
      consistency and whether breath-hold is maintained. Voluntary breath-hold uses the
      distance moved by the anterior and lateral reference marks (tattoos) away from
      the treatment room lasers in breath-hold to monitor consistency at CT-planning
      and treatment setup. Light fields are then used to monitor breath-hold
      consistency prior to and during radiotherapy delivery. 

PMID- 25046662
TI  - Velopharyngeal Insufficiency Rates After Delayed Cleft Palate Repair: Lessons
      Learned From Internationally Adopted Patients.
AB  - Most surgeons recommend cleft palate repair between 6 and 12 months of age.
      Internationally adopted patients often undergo delayed repair due to social
      circumstances. There are few outcomes studies on this population. We conducted a
      13-year retrospective review of all patients undergoing primary cleft palate
      repair at a single tertiary-care academic medical center between 1993 and 2006.
      The primary outcome was velopharyngeal insufficiency, defined as the
      recommendation for corrective surgery after multiple formal speech assessments.
      Two hundred one patients (102 males and 99 females) were identified. One hundred
      eighty-three repairs were performed before 18 months of age (standard repair
      group). Eighteen repairs were performed after 18 months of age (delayed repair
      group), with international adoption being a circumstance in 16 cases. The delayed
      and standard repair groups were similar with regard to sex, presence of
      craniofacial syndrome, Veau class, cleft size and laterality, type of repair, and
      operating surgeon. Mean follow-up was 9.3 years, with minimum follow-up of 5.0
      years. Six (33%) of 18 patients in the delayed repair group developed
      velopharyngeal insufficiency compared to 23 (13%) of 183 in the standard repair
      group (P = 0.03 by Fisher exact test). These data demonstrate that
      internationally adopted patients undergoing delayed palate repair suffer
      especially poor speech outcomes. Physiologic differences in patients undergoing
      late repair, as well as social factors including adaptation to a new language and
      culture, may be factors. Early repair should be performed when possible. 

PMID- 25046663
TI  - Biomedical implant capsule formation: lessons learned and the road ahead.
AB  - Clinicians and investigators have been implanting biomedical devices into
      patients and experimental animals for centuries. There is a characteristic
      complex inflammatory response to the presence of the biomedical device with
      diverse cell signaling, followed by migration of fibroblasts to the implant
      surface and the eventual walling off of the implant in a collagen capsule. If the
      device is to interact with the surrounding tissues, the collagen envelope will
      eventually incapacitate the device or myofibroblasts can cause capsular
      contracture with resulting distortion, migration, or firmness. This review
      analyzes the various tactics used in the past to modify or control capsule
      formation with suggestions for future investigative approaches. 

PMID- 25046664
TI  - Inpatient versus outpatient cleft lip repair and alveolar bone grafting: a cost
      analysis.
AB  - BACKGROUND: The lifetime cost of a child with an orofacial cleft is estimated at
      $101,000, which amounts to $697 million total for those born each year with
      orofacial clefts. There has been a trend toward outpatient procedures for cleft
      lip repair (CLR) and alveolar bone grafting (ABG), and studies have shown no
      disparities in safety or outcome between inpatient and ambulatory treatment. The
      financial implications of outpatient versus inpatient procedures have not been
      compared. METHODS: Financial data were collected for outpatient (n = 33) and
      inpatient (n = 2) CLR, as well as outpatient (n = 7) and inpatient (n = 5) ABG
      during a 5-year period at our institution. We examined hospital charges and
      reimbursement for these procedures by private insurance plans and Medicaid
      Managed Care (MMC) plans. RESULTS: The average total reimbursements for inpatient
      and outpatient CLR were similar at $6848 and $5557, respectively. Average
      facility reimbursement for CLR was greater for inpatient ($5344) than outpatient
      ($4291) procedures. Average professional reimbursement was similar between
      inpatient ($1504) and outpatient ($1266) CLR.For ABG, the average total inpatient
      reimbursement was $14,573, whereas outpatient was $8877. Average facility
      reimbursements were greater for inpatient ($12,398) than outpatient ($7183) ABG.
      Average professional reimbursement was similar between inpatient ($2175) and
      outpatient ($1693) ABG, with 35% and 31% of charges reimbursed, respectively.A
      substantial difference existed between reimbursements based on insurance types
      for both outpatient CLR and outpatient ABG. On average for CLR, commercial payers
      reimbursed 52% ($7344) of overall charges, whereas Medicaid and MMC reimbursed 9%
      ($1447). For ABG, commercial payers reimbursed an average of 78% ($11,950) of
      overall charges, whereas Medicaid and MMC reimbursed 10% ($1192). CONCLUSIONS:
      Fewer patients' insurance companies are reimbursing for inpatient stays; in many
      cases, even patients who remain hospitalized up to 48 hours are treated as "day
      surgery" from a reimbursement perspective. For outpatient surgery, a greater
      percentage of CLR and ABG charges were successfully recouped compared to
      inpatient surgery. Awareness of higher payment for inpatient surgery and
      potential savings through use of the outpatient setting is crucial for hospitals
      and the US health care system as a whole.

PMID- 25046665
TI  - Reexamining free flap breast reconstruction in the community and university
      setting: is there a difference?
AB  - BACKGROUND: This study aimed to compare free flap breast reconstruction outcomes
      in community and university settings to determine whether the latter is necessary
      for successful performance of this complex procedure. METHODS: Free tissue
      transfer procedures for breast reconstruction from 1 university and 1 community
      hospital performed between 2005 and 2011 were included. Procedures were performed
      by the same 2 surgeons at both institutions. Demographics and outcome measures
      were evaluated. RESULTS: Of the 1293 free tissue breast reconstructions
      performed, 99 (7.7%) were performed in a community hospital and 1194 (92.3%) were
      performed in a university center. No differences were noted in demographics,
      comorbidities, or type of free flap reconstruction. However, a number of
      perioperative characteristics differed. In the community setting, operative time
      was less (7.3 vs 8.3 hours, P < 0.0001), estimated blood loss was higher (330 vs
      248 mL, P < 0.0001), and blood transfusions were more prevalent (24.6% vs 8.3%, P
      < 0.0001). Furthermore, no significant differences were noted in overall
      postoperative complications, although a higher rate of abdominal wound infections
      was noted in the community setting (7.2% vs 2.6%, P = 0.03). The mean number of
      hospital days was similar between the community and the university (should
      include value P = 0.44). CONCLUSIONS: Although slight differences were noted in a
      number of perioperative variables and wound complications, we conclude that the
      key to a successful free tissue transfer reconstruction is in the expertise of
      the surgeon and not the setting in which it is performed. Despite its complexity,
      free flap breast reconstruction can be safely and successfully performed in the
      community setting.

PMID- 25046666
TI  - The limited incision harvest of the rectus femoris flap for complex groin wound
      management.
AB  - BACKGROUND: Muscle flaps can be effective in the protocol of complex groin wound
      management, yet donor-site morbidity remains a continued concern. The purpose of
      this study was to present a minimally invasive approach to the harvest of the
      rectus femoris flap (RFF) for groin wound vascularized tissue coverage. PATIENTS
      AND METHODS: A retrospective study examined all patients undergoing RFF coverage
      and reconstruction of a complex groin wound between July 1, 2010, and December
      31, 2011. During the study period, the senior author (S.K.K.) performed all RFF
      harvests through a minimally invasive approach, whereas all other surgeons
      performed the RFF harvest through a standard approach. Patients who underwent a
      minimally invasive RFF approach were compared with those who underwent the
      standard incision. RESULTS: Forty-three patients underwent RFF coverage
      procedures, 11 of which were carried out using the minimally invasive technique.
      The patients in the minimally invasive cohort were older (P = 0.03) but had
      similar rates of medical comorbidities. Minimally invasive RFF harvests were more
      commonly performed in the planned, salvage setting (P = 0.03). No difference was
      found in the vascular surgery procedure type (P = 0.13), presence of exposed
      prosthetic graft material (0.2), or rate of culture-positive wound (P = 0.67).
      Importantly, no differences in operative time (184.4 [45.5] minutes vs 169.3
      [31.7] minutes, P = 0.45) or postoperative complications were observed, with no
      graft losses or major limb-related morbidity in either group. CONCLUSIONS: The
      RFF continues to be a workhorse flap for complex groin wounds, most often in the
      salvage setting. This study demonstrates that a minimally invasive approach can
      be used for flap harvest with equivalent results to that of the standard
      longitudinal incision.

PMID- 25046667
TI  - Prospective, randomized evaluation of endoscopic versus open carpal tunnel
      release in bilateral carpal tunnel syndrome: an interim analysis.
AB  - BACKGROUND: Most randomized trials have shown similar results with endoscopic
      carpal tunnel release (ECTR) and open carpal tunnel release (OCTR); however,
      there are studies suggesting less postoperative pain, faster improvement in grip
      and pinch strength, and earlier return to work with the endoscopic technique. The
      goal of this study was to prospectively examine subjective and functional
      outcomes, satisfaction, and complications after both ECTR and OCTR in the
      opposite hands of the same patient, serving as their own control. METHODS: This
      was a prospective, randomized study in which patients underwent surgery for
      bilateral carpal tunnel syndrome. The first carpal tunnel release was performed
      on the most symptomatic hand-determined by the patient. Operative approach was
      randomly assigned and, approximately 1 month later, the alternative technique was
      performed on the contralateral side. Demographic data were obtained, and
      functional outcomes were recorded preoperatively and postoperatively, including
      pain score, 2-point discrimination, Semmes-Weinstein monofilament testing, thenar
      strength, and overall grip strength. The carpal tunnel syndrome-functional status
      score and carpal tunnel syndrome-symptom severity score were recorded before
      surgery and at 2, 4, 8, 12, and 24 weeks postoperatively. Overall satisfaction
      with each technique was recorded at the conclusion of the study. RESULTS:
      Currently, 25 subjects have completed final visit testing. There were no
      differences in pain score, 2-point discrimination, Semmes-Weinstein monofilament
      testing, thenar strength, or overall grip strength at any of the postoperative
      time points. Carpal tunnel syndrome-symptom severity score and carpal tunnel
      syndrome-functional status score were not significantly different between groups
      at any of the evaluations. Overall satisfaction, where patients recorded a number
      from 0 to 100, was significantly greater in the ECTR group (95.95 vs 91.60, P =
      0.04). There were no complications with either technique. DISCUSSION: This
      interim analysis, using the same patient as an internal control, suggests that
      both OCTR and ECTR are well tolerated with no differences in functional outcomes,
      symptom severity and functional status questionnaires, or complications. Although
      there were no differences between groups using our study metrics, patients still
      preferred the ECTR, demonstrated by significantly higher overall satisfaction
      scores at the conclusion of the study.

PMID- 25046668
TI  - An effective method to access recipient vessels outside the zone of injury in
      free flap reconstruction of the lower extremity.
AB  - INTRODUCTION: A principle of microvascular surgery in lower extremity
      reconstruction is to identify recipient vessels and perform the anastomosis
      outside the zone of injury. Microsurgeons will often create an incision that
      extends from the wound several centimeters proximally to access the recipient
      vessels through healthy tissue. This iatrogenic wound, however, traverses the
      zone of injury and is susceptible to delayed healing and wound breakdown. These
      complications can be avoided by creating a unique incision proximal to the zone
      of injury through which the recipient vessels are dissected and the anastomosis
      performed. METHODS: In 13 consecutive patients with lower extremity wounds
      requiring free flap reconstruction, a remote incision was made in healthy tissue
      proximal to the defect to access the recipient vessels outside the zone of
      injury. The pedicle was tunneled in the subcutaneous plane from the wound to this
      site, and the anastomosis was performed. The flap was inset in the standard
      fashion, and the remote incision was closed in layers. RESULTS: There were 3
      female and 10 male patients, and the median age was 65 years (18-85 years).
      Etiology of the wounds was traumatic (3 acute, 7 chronic), oncologic (2), and
      ischemic (1). Defects varied in size and were primarily located on the distal
      third of the extremity. Free flaps included radial forearm (4), anterolateral
      thigh (4), gracilis (2), vastus (1), latissimus dorsi (1), and parascapular (1).
      Postoperatively, there were no major complications related to the flap or any
      flap losses. There was 1 donor site hematoma requiring operative evacuation.
      There were no complications associated with the anastomotic incision.
      CONCLUSIONS: Accessing the recipient vessels via a separate proximal incision in
      lower extremity free flap reconstruction allows excellent exposure outside the
      zone of injury, avoids wound healing problems, and protects the pedicle from
      injury in the setting of multiple-staged procedures.

PMID- 25046669
TI  - Population preferences of undergoing brachioplasty for arm laxity.
AB  - BACKGROUND: The number of patients requesting surgical procedures performed for
      brachioplasty and massive weight loss is increasing. The authors set out to
      quantify the health state utility outcome assessment of living with arm deformity
      requiring brachioplasty. METHODS: Utility assessments using the visual analog
      scale (VAS), time trade-off (TTO), and standard gamble (SG) were used to obtain
      utilities scores for arm deformity, monocular blindness, and binocular blindness
      from a sample of the general population and medical students. Linear regression
      and Student t test were used for statistical analysis. A P value less than 0.05
      was deemed statistically significant. RESULTS: All the measures for arm deformity
      of the 107 volunteers (VAS, 0.80 +/- 0.14; TTO, 0.91 +/- 0.12; SG, 0.94 +/- 0.10)
      were significantly different (P < 0.001) from the corresponding measures for
      monocular blindness and binocular blindness. When compared to the sample of the
      general population, having a medical education demonstrated a statistical
      significance of being less likely to trade years of life and less likely to
      gamble risk of death for a procedure such as a brachioplasty. Race and sex were
      not statistically significant independent predictors of risk acceptance.
      CONCLUSIONS: We have objectified the health state of living with upper arm
      deformity requiring brachioplasty. Utility outcome scores (VAS, 0.80 +/- 0.14;
      TTO, 0.91 +/- 0.12; SG, 0.94 +/- 0.10) were comparable to living with health
      states such as aging neck needing rejuvenation, excess skin in the thighs
      necessitating thigh lift, and massive weight loss requiring panniculectomy based
      on previously reported studies.

PMID- 25046670
TI  - Pulmonary Function After Pedicled Transverse Rectus Abdominis Musculocutaneous
      Flap Breast Reconstruction.
AB  - Tight abdominal closures, as can be seen during transverse rectus abdominis
      musculocutaneous (TRAM) flap breast reconstruction, have been shown to increase
      intra-abdominal pressure, thereby decreasing thoracopulmonary compliance and
      increasing the workload of breathing. The purpose of this article was to
      quantitate pulmonary function in patients who underwent pedicled TRAM flap breast
      reconstruction.A prospective clinical trial was conducted involving 22 women
      undergoing unilateral or bilateral pedicled TRAM flap breast reconstruction.
      Pulmonary function testing was conducted 1 week before the operation, 24 hours
      postoperatively, and 2 months postoperatively. The patients were stratified by
      age (<50 years vs >=50 years), type of TRAM flap (unilateral vs bilateral),
      tobacco use (smoker vs nonsmoker), and body mass index. Changes were analyzed
      using 1-way repeated-measures analysis of variance and paired t tests. All
      comparisons used a 2-tailed test at the 0.05 level of significance.Other than
      residual volume, the 24-hour postoperative values were significantly lower than
      the preoperative values. The smokers had less change in functional residual
      capacity, total lung capacity, and forced vital capacity values than the
      nonsmokers at 24 hours postoperatively; however, they were noted to have
      decreased pulmonary function at baseline. The patients 50 years or older had
      significantly greater decline in functional residual capacity and residual volume
      compared with the younger cohort. No significant difference in pulmonary function
      testing values existed between those undergoing bilateral versus unilateral
      pedicled TRAM flap reconstruction. Pulmonary function tests returned to baseline
      at 2-month follow-up.Pulmonary function test values were significantly decreased
      at 24 hours after pedicled TRAM flap breast reconstruction. 

PMID- 25046671
TI  - Island thoracodorsal artery perforator-based V-Y advancement flap after radical
      excision of axillary hidradenitis.

PMID- 25046672
TI  - Thirty-Year Follow-up of Total Hand Replantation: A Case Report.
AB  - The loss of a limb is a devastating yet relatively common injury with a vast
      panoply of effects. Beyond the obvious potential for the loss of livelihood are
      profound social, psychological, and aesthetic consequences. Thus, despite
      significant improvements in functional prostheses and rehabilitation for
      traumatic hand amputations, the option for replantation should always be
      carefully considered. We present a case of a total hand replantation at the level
      of the wrist performed 30 years ago, which to our knowledge exceeds the longest
      reported follow-up by 11 years. The excellent outcome observed in this patient
      demonstrates the importance of presurgical planning and analysis of the amputated
      segment, the utility of therapy, and the durable functionality of extremity
      replantation over an extended period. 

PMID- 25046673
TI  - A Novel Method for Correction of the Hypoplastic Pixie Earlobe Deformity: V-Y
      Advancement Flap and Dermofat Graft.
AB  - Pixie ear deformity is a condition in which the inferior edge of the helix of the
      ear is attached to the cheek without a convolutional notch at the ear lobule
      cheek junction. Numerous surgical techniques have been proposed to correct pixie
      earlobe deformities. However, several of these techniques result in anterior or
      inferior scars of the ear lobules or dog-ear deformities. Such visible scarring
      detracts from the esthetics of the ear lobule.We report a novel method for the
      correction of pixie ear deformities in patients with small ear lobules. A
      hypoplastic ear lobule was expanded by a V-Y advancement flap designed on the
      posterior aspect of the ear lobule, and a dermofat graft was placed in the
      subcutaneous layer under the advanced flap. As a result, the pixie ear lobe
      deformity was camouflaged by the expanded ear lobule. Moreover, no scars appeared
      on the anterior or inferior sides of the ear lobule, and a natural appearance of
      the ear lobe was achieved.We conclude that this method is a feasible alternative
      surgical option for hypoplastic pixie ear lobe deformities to avoid visible
      scarring in the anterior or inferior aspects of the ear lobe. 

PMID- 25046674
TI  - A Bilobed Thoracoabdominal Myocutaneous Flap for Large Thoracic Defects.

PMID- 25046675
TI  - Is It Possible to Increase Flap Viability by Hydrostatic Dilation?: An
      Experimental Study in the Rat Abdominal Fasciocutaneous Flap Model.
AB  - INTRODUCTION: Ergun et al previously demonstrated the efficacy of hydrostatic
      dilation in a TRAM flap model in an experimental study. We investigated the
      effect of hydrostatic dilation on a fasciocutaneous flap model. METHODS: Eighteen
      female Wistar rats were equally divided into 3 groups, of which 1 served as a
      control. In the second, the abdominal fasciocutaneous flap surgical delay
      procedure was performed by division of the left superficial inferior epigastric
      (SIE) vessels. In the third, hydrostatic dilation was performed on the left SIE
      artery and vein, with a mean pressure of 300 mm Hg, while elevating the flap on
      the right-sided SIE pedicle. The groups were compared by microangiography and by
      the survival ratio of abdominal flaps 7 days after elevation. RESULTS: The mean
      (SD) flap necrosis rates were as follows: control group, 44.75% (4.31%); delay
      group, 33.32% (7.11%); and hydrostatic dilation group, 32.51% (5.03%). There was
      a significant difference between the control group and the other 2 groups (P <
      0.05). There was no difference between the delay and hydrostatic dilation groups
      with respect to surface area necrosis. The microangiographies showed remarkable
      increased vascularity in the delay and hydrostatic dilation groups. CONCLUSIONS:
      Hydrostatic dilation is a new method of enhancing flap viability that could be
      used in clinical cases in place of surgical delay once further studies and
      clinical trials are completed.

PMID- 25046676
TI  - The impact of electronic medical record implementation on the outpatient volumes
      of a midsize academic center.
AB  - BACKGROUND: Despite the proposed clinical advantages of electronic medical
      records (EMRs), many questions remain regarding how EMRs may limit the number of
      patients a provider can see on a day-to-day basis. In this study, we measured the
      impact of EMR implementation on outpatient volumes in the setting of a midsize
      academic medical center (AMC) in the southeast. METHODS: The AMC outpatient visit
      volumes of two 12-month periods, one before and one after the EMR implementation,
      were collected. The mean monthly outpatient visits before and after EMR
      implementation were compared using the 2-tailed Student t test without assumption
      for equal variance. We also normalized the total annual visits to the number of
      full-time equivalent physicians. Power calculation was performed to measure type
      II error whenever P value was greater than 0.05. RESULTS: There was an 8.37%
      increase in total outpatient visits after EMR implementation, with the monthly
      number of patients seen increasing from a mean (SD) of 25,763.75 (1673.96) to
      27,919.92 (2229.07) (P = 0.018). However, this increase disappears when
      normalized to full-time equivalent. After conducting multiple subunit analyses of
      a multiphysician primary care clinic (Family Medicine), specialty clinic (Plastic
      Surgery), and single-physician specialty clinic (Pediatric Plastic Surgery), we
      also did not find a statistically significant difference in outpatient clinic
      volumes after EMR implementation. CONCLUSIONS: Despite the burdensome time
      requirements many physicians subjectively attribute to EMRs, this study shows
      that the EMR has not really caused a statistically significant decrease in
      outpatient volumes in the setting of a midsize AMC.

PMID- 25046677
TI  - Bipolar Latissimus Dorsi Transfer for Restoration of Pectoralis Major Function in
      Poland Syndrome.
AB  - BACKGROUND: Poland syndrome typically presents as a unilateral congenital
      complete or partial absence of the pectoralis major muscle, variably with other
      associated anomalies. Reconstruction of the defect typically concentrates on
      aesthetic restoration with functional outcomes being unsuccessful or limited. We
      present an innovative means of true muscle transfer that provided functional
      benefit to increase upper extremity strength. CASE REPORT: A 16-year-old
      adolescent boy with Poland syndrome manifesting as left pectoralis major muscle
      agenesis wished to undergo functional reconstruction. He wanted to play on his
      high school football team, but could not meet the minimum weightlifting
      requirements. An ipsilateral latissimus dorsi muscle bipolar functional transfer
      was done with bone-anchored inset into the sternum and humerus so that muscle
      flexion would replace the absent pectoralis major. A progressive weight training
      program was then instituted postoperatively. At 9 months, a significant increase
      in left upper extremity strength was confirmed. The patient ultimately was able
      to surpass the weightlifting requirements for his high school football team, and
      joined the team. CONCLUSIONS: Our highlighted procedure restored functional
      outcome using both plastic surgical principles and orthopedic techniques for
      muscle and tendon repair: bipolar muscle transfer and load-bearing muscle inset.
      Heretofore, transfer of the latissimus for provision of pectoralis major function
      has not been reported. Functional reconstruction was possible due to stable,
      bipolar muscle transfer with load-bearing muscle attachments into cortical bone
      of the anterior sternum and anteromedial aspect of the humerus. The techniques
      described should be within the skill set of most plastic surgeons, so that
      functional restoration for those with Poland syndrome is possible and accessible.

PMID- 25046678
TI  - Acute marjolin ulcers: a nebulous diagnosis.

PMID- 25046679
TI  - Lateral Arm Free Flap With Preservation of the Posterior Antebrachial Cutaneous
      Nerve.
AB  - The lateral arm free flap offers many advantages in reconstruction of soft tissue
      defect and reconstruction of extremities. However, this free flap is associated
      with sensory loss at the posterior forearm due to injury of the posterior
      antebrachial cutaneous nerve (PABCN).The PABCN-sparing lateral arm free flaps
      were performed in 19 patients with various soft tissue defects of the extremity,
      and the outcomes of free flap reconstructions using this modification are
      evaluated. All flaps survived without partial necrosis. Three patients
      experienced transient sensory loss in the posterior area of the forearm after
      flap harvest.In this study, lateral arm free flaps can be elevated without
      necessarily sacrificing the PABCN. This nerve-sparing modification decreases the
      donor-site morbidity of lateral arm free flaps and further increases the overall
      usefulness of this flap in soft tissue reconstructions of the extremities. 

PMID- 25046680
TI  - Physical aging, the local dynamics of glass-forming polymers under nanoscale
      confinement.
AB  - The glass transition temperature marks a point below which a material's
      properties change significantly, and it is well-established that confinement to
      the nanoscale modifies the properties of glass-forming materials. We use
      molecular dynamics simulations to investigate the dynamics and aging behavior of
      model glass-forming polymers near and below the glass transition temperature of
      bulk and confined films. We show that both relaxation times and physical age
      rates vary similarly throughout a free-standing polymer film at temperatures
      close to the bulk glass transition temperature, where the surfaces have both
      lower relaxation times and physical age rates. Moreover, we provide evidence
      suggesting that string lengths in the bulk control dynamic length scales in the
      film. This realization, combined with the similarity between aging behavior and
      dynamic profiles, has implications for design rationale in the microelectronics
      industry. 

PMID- 25046681
TI  - Argument for prostate cancer screening in populations of African-Caribbean
      origin.

PMID- 25046682
TI  - [Pathogenicity of Mycobacterium kansasii].
AB  - BACKGROUND: In a recent prospective study on pulmonary infections with non
      tuberculous mycobacteria (NTM) led by the WATL group, disease rates in patients
      with M. kansasii infection were found to be 100 %. In the present study we re
      evaluated the pathogenicity of M. kansasii infections in a large lung diseases
      treatment center in Berlin (Lungenklinik Heckeshorn). METHODS: All patients in
      whose respiratory specimen cultures M. kansasii was detected between January 2003
      and June 2013 were included. The 2007 ATS diagnostic criteria were applied to
      differentiate disease from asymptomatic infection. The strains were further
      investigated by sequencing of the 16S-23S rDNA internal transcribed spacer (ITS)
      region. RESULTS: We evaluated 43 consecutive cases. Complete patient data were
      available in 38 cases. In one patient, no culture results were obtained, in 37
      patients M. kansasii was isolated and patient data could be retrieved. In 25/37
      patients (68 %) clinical disease was present so that a specific treatment was
      initiated (underlying diseases were COPD in 8/25 (32 %), bronchiectasis in 5/25
      (20 %), TB scar or scar due to prior chest surgery in 3/25 (12 %) and alcohol
      abuse in 4/25 (16 %)). Twelve out of 37 patients (32 %) were found to be
      colonized or asymptomatically infected (underlying diseases were COPD in 7/12 (58
      %), bronchiectasis in 3/12 (25 %) and TB scar or scar due to prior chest surgery
      in 3/12 (25 %)). Sequencing results identified 30 strains as genotype I, and 2
      strains as genotype II. In 22/30 cases (73 %) genotype I was considered
      pathogenic. CONCLUSIONS: In our cohort, we could not confirm the high M. kansasii
      pathogenicity of 100 % found in a previous multi-center study; we therefore
      support the clinical and semiquantitative microbiologic diagnostic criteria also
      for infection with M. kansasii.

PMID- 25046683
TI  - [Statement to long term oxygen therapy].

PMID- 25046684
TI  - [Transfusion-related acute lung injury (TRALI)].
AB  - Transfusion-related acute lung injury (TRALI) is primarily caused by transfusion
      of fresh frozen plasma or platelet concentrates and occurs by definition within 6
      hours after transfusion with acute shortness of breath, hypoxemia and
      radiographically detectable bilateral infiltrates of the lung. Mostly leucocyte
      antibodies in the plasma of the blood donor (immunogenic TRALI) are responsible.
      Apart from antibodies, other substances such as biologically active lipids,
      mainly arising from the storage of platelet and red blood cell concentrates, can
      activate neutrophilic granulocytes and trigger a non-immunogenic TRALI.
      Pathophysiologically, granulocytes in the capillaries of the lung vessels release
      oxygen radicals and enzymes which damage the endothelial cells and cause
      pulmonary edema. Therapeutically, nasal oxygen administration may be sufficient.
      In severe cases, mechanical ventilation, invasive hemodynamic monitoring and
      fluid intake are required. Diuretics should be avoided. The administration of
      glucocorticoids is controversial. Antibody-related TRALI reactions occurred
      mainly after transfusion of fresh frozen plasma, which had been obtained from
      womenimmunized during pregnancy against leukocyte antigens. Therefore, in
      Germany, since 2009 only plasma from female donors without a history of prior or
      current pregnancy or negative testing for antibodies against HLA I, II or HNA has
      been used with the result that since then no TRALI-related death has been
      registered. 

PMID- 25046685
TI  - A global database of C4 photosynthesis in grasses.

PMID- 25046686
TI  - Banana resistant starch and its effects on constipation model mice.
AB  - Banana resistant starch (BRS) was extracted to investigate the structural
      properties of BRS, its effects on the gastrointestinal transit, and dejecta of
      normal and experimentally constipated mice. The mouse constipation model was
      induced by diphenoxylate administration. The BRS administered mice were divided
      into three groups and gavaged with 1.0, 2.0, or 4.0 g/kg body weight BRS per day.
      The small intestinal movement, time of the first black dejecta, dejecta granules,
      weight and their moisture content, body weight, and food intake of mice were
      studied. Results showed that the BRS particles were oval and spindly and some
      light cracks and pits were in the surface. The degree of crystallinity of BRS was
      23.13%; the main diffraction peaks were at 2(theta) 15.14, 17.38, 20.08, and
      22.51. The degree of polymerization of BRS was 81.16 and the number-average
      molecular weight was 13147.92 Da, as determined by the reducing terminal method.
      In animal experiments, BRS at the dose of 4.0 g/kg body weight per day was able
      to increase the gastrointestinal propulsive rate, and BRS at the doses of 2.0 and
      4.0 g/kg body weight per day was found to shorten the start time of defecation by
      observing the first black dejecta exhaust. However, there were no influences of
      BRS on the dejecta moisture content, the dejecta granules and their weight, body
      weight, or daily food intake in mice. BRS was effective in accelerating the
      movement of the small intestine and in shortening the start time of defecation,
      but did not impact body weight and food intake. Therefore, BRS had the potential
      to be useful for improving intestinal motility during constipation.

PMID- 25046687
TI  - Biomineralized anisotropic gold microplate-macrophage interactions reveal
      frustrated phagocytosis-like phenomenon: a novel paclitaxel drug delivery
      vehicle.
AB  - This study reports a facile biomineralization route for gold microplates (GMPs)
      synthesis using bovine serum albumin (BSA) as a reductant and stabilizing agent.
      Adding BSA to HAuCl4 solution yields spontaneous versatile anisotropic and
      partially hollow GMPs upon aging. We hypothesize that the instantaneous protein
      denaturation at low pH enabled access to serine and threonine hydroxyl, and
      sulfhydryl groups of BSA, which act as a reductant and stabilizer, respectively.
      This reaction could be hastened by increasing the temperature well beyond 65 
      degrees C. Transmission electron microscopy/X-ray diffraction studies revealed
      highly crystalline and anisotropic structures (triangle, pentagon, and
      rectangle). Atomic force microscopy/scanning electron microscopy analyses
      demonstrated unique morphology of microplates with a partially void core and BSA
      mineralized edge structure. RAW 264.7 mice peritoneal macrophage-microplate
      interaction studies using live cell confocal imaging reveal that cells are
      capable of selectively internalizing smaller GMPs. Large GMPs are preferentially
      picked with sharp vertices but cannot be internalized and exhibit frustrated
      phagocytosis-like phenomenon. We explored particle phagocytosis as an actin
      mediated process that recruits phagosome-like acidic organelles, shown by a
      lysosensor probe technique. The biocompatible GMPs exhibited ~70% paclitaxel
      (PCL) loading and sustained release of PCL, showing antitumor activity with the
      MCF-7 cell line, and could be a novel drug carrier for breast cancer therapy. 

PMID- 25046688
TI  - The lab finally comes to the chip!

PMID- 25046689
TI  - Health and air quality benefits of policies to reduce coal-fired power plant
      emissions: a case study in North Carolina.
AB  - We analyzed sulfur dioxide (SO2) emissions and fine particulate sulfate (PM2.5
      sulfate) concentrations in the southeastern United States during 2002-2012, in
      order to evaluate the health impacts in North Carolina (NC) of the NC Clean
      Smokestacks Act of 2002. This state law required progressive reductions (beyond
      those mandated by federal rules) in pollutant emissions from NC's coal-fired
      power plants. Although coal-fired power plants remain NC's leading SO2 source, a
      trend analysis shows significant declines in SO2 emissions (-20.3%/year) and
      PM2.5 sulfate concentrations (-8.7%/year) since passage of the act. Emissions
      reductions were significantly greater in NC than in neighboring states, and
      emissions and PM2.5 sulfate concentration reductions were highest in NC's
      piedmont region, where 9 of the state's 14 major coal-fired power plants are
      located. Our risk model estimates that these air quality improvements decreased
      the risk of premature death attributable to PM2.5 sulfate in NC by about 63%,
      resulting in an estimated 1700 (95% CI: 1500, 1800) deaths prevented in 2012.
      These findings lend support to recent studies predicting that implementing the
      proposed federal Cross-State Air Pollution Rule (recently upheld by the U.S.
      Supreme Court) could substantially decrease U.S. premature deaths attributable to
      coal-fired power plant emissions. 

PMID- 25046690
TI  - Regiospecific synthesis of 2-halo-3-(2'-glucalyl)benzo[b]thiophenes.
AB  - A regiospecific synthetic strategy for the synthesis of 2-chloro-3-substituted
      benzo[b]thiophenes is developed via a dichlorocarbene insertion and sigmatropic
      rearrangement of an in situ generated ylide. The current protocol provides a
      reversed regiochemistry to the commonly employed electrophilic cyclization
      reaction for the synthesis of benzo[b]thiophenes and access to their hitherto
      under-represented chlorinated derivatives. 

PMID- 25046691
TI  - Coexisting prostate cancer found at the time of holmium laser enucleation of the
      prostate for benign prostatic hyperplasia: predicting its presence and grade in
      analyzed tissue.
AB  - OBJECTIVE: To determine the incidence of prostate cancer identified on holmium
      laser enucleation of the prostate (HoLEP) specimens and evaluate variables
      associated with prostate cancer identification. PATIENTS AND METHODS: All
      patients undergoing HoLEP between 1998 and 2013 were identified. Patients with a
      known history of prostate cancer were excluded. Multivariable logistic regression
      assessed variables associated with identification of prostate cancer on HoLEP
      specimens and Gleason 7 or higher prostate cancer among the malignant cases. The
      Gleason grade was used as a proxy for disease severity. Each of the models was
      adjusted for age, preoperative prostate-specific antigen (PSA), and HoLEP
      specimen weight. RESULTS: The cohort comprised 1272 patients, of whom 103 (8.1%)
      had prostate cancer identified. Prostate cancer cases had higher pre-HoLEP PSA
      (p=0.06) but lower HoLEP specimen weight (p=0.01). On multivariate logistic
      regression, age and preoperative PSA were associated with increased odds of
      prostate cancer being present (p<0.01 each), while increasing HoLEP specimen
      weight was associated with decreased odds of prostate cancer (p<0.001). Men older
      than 80 had 20% predicted probability of being diagnosed with prostate cancer.
      Seventy-eight percent of prostate cancer cases were Gleason 6 or less. The pre
      HoLEP PSA was associated with increased adjusted odds of intermediate- or high
      grade prostate cancer. CONCLUSION: Prostate cancer identified by HoLEP is not
      uncommon, but is generally a low-risk disease. Older patients with smaller
      prostate glands have the highest odds of prostate cancer identification.

PMID- 25046693
TI  - Dispersed Cu2O octahedrons on h-BN nanosheets for p-nitrophenol reduction.
AB  - We demonstrate here that two-dimensional boron nitride (h-BN) nanosheets can be
      employed as a robust supporting substrate to incorporate function metal oxides.
      The Cu2O@h-BN composites are thus obtained by dispersing Cu2O octahedrons on the
      surfaces of h-BN nanosheets. The -OH and -NH groups on the surfaces of h-BN
      nanosheets are found to be beneficial for anchoring Cu2O octahedrons. Moreover,
      the Cu2O@h-BN composites exhibit superior activity for the reduction of p
      nitrophenol to pure Cu2O crystals and h-BN nanosheets. The h-BN component in the
      composites plays a critical role in the formation and adsorbing of the p
      nitrophenolate ions, and, at the same time, Cu2O components react with brohydride
      ions and transfer a surface hydrogen species and electrons, resulting in the
      reduction of p-nitrophenol into p-aminophenol. Our results provide a new approach
      for the rational design and development of metal oxides composites and open the
      way to a range of important applications of h-BN-based materials. 

PMID- 25046692
TI  - Pivotal role of phospholipase D1 in tumor necrosis factor-alpha-mediated
      inflammation and scar formation after myocardial ischemia and reperfusion in
      mice.
AB  - Myocardial inflammation is critical for ventricular remodeling after ischemia.
      Phospholipid mediators play an important role in inflammatory processes. In the
      plasma membrane they are degraded by phospholipase D1 (PLD1). PLD1 was shown to
      be critically involved in ischemic cardiovascular events. Moreover, PLD1 is
      coupled to tumor necrosis factor-alpha signaling and inflammatory processes.
      However, the impact of PLD1 in inflammatory cardiovascular disease remains
      elusive. Here, we analyzed the impact of PLD1 in tumor necrosis factor-alpha
      mediated activation of monocytes after myocardial ischemia and reperfusion using
      a mouse model of myocardial infarction. PLD1 expression was highly up-regulated
      in the myocardium after ischemia/reperfusion. Genetic ablation of PLD1 led to
      defective cell adhesion and migration of inflammatory cells into the infarct
      border zone 24 hours after ischemia/reperfusion injury, likely owing to reduced
      tumor necrosis factor-alpha expression and release, followed by impaired nuclear
      factor-kappaB activation and interleukin-1 release. Moreover, PLD1 was found to
      be important for transforming growth factor-beta secretion and smooth muscle
      alpha-actin expression of cardiac fibroblasts because myofibroblast
      differentiation and interstitial collagen deposition were altered in Pld1(-/-)
      mice. Consequently, infarct size was increased and left ventricular function was
      impaired 28 days after myocardial infarction in Pld1(-/-) mice. Our results
      indicate that PLD1 is crucial for tumor necrosis factor-alpha-mediated
      inflammation and transforming growth factor-beta-mediated collagen scar
      formation, thereby augmenting cardiac left ventricular function after
      ischemia/reperfusion. 

PMID- 25046694
TI  - Highly hydrated deformable polyethylene glycol-tethered lipid bilayers.
AB  - The realization of a solid-supported lipid bilayer acting as a workbench for the
      study of membrane processes is a difficult task. For robustness, the bilayer has
      to be tethered to the substrate. At the same time, diffusion of the lipids and
      plastic deformations of the membrane should not be obstructed. Furthermore, a
      highly hydrated surrounding is mandatory. Here, we show that grafting of a
      polyethylene glycol-lipid construct (PEG2000-DSPE) to a silicon oxide surface via
      multiple-step silane chemistry and subsequent deposition of lipids by spin
      coating result in a cushioned membrane that has the desired properties. Neutron
      and X-ray reflectometry measurements are combined to access thickness, density,
      and hydration of the bilayer and the PEG cushion. We observe a spacer of 55 A
      thickness between lipid bilayer and silicon-oxide surface with a rather high
      hydration of up to 90 +/- 3% water. While 11.5 +/- 3% of the lipids are grafted
      to the surface, as determined from the neutron data, the diffusion constant of
      the lipids, as probed by diffusion of 0.5% Texas Red labeled lipids, remains
      rather large (D = 2.1 +/- 0.1 MUm(2)/s), which is a reduction of only 12%
      compared to a supported lipid bilayer reference without immobilized lipids.
      Finally, AFM indentation confirms the plastic behavior of the membrane against
      deformation. We show that rupture of the bilayer does not occur before the
      deformation exceeds 40 A. Altogether, the presented PEG-tethered lipid bilayer
      mimics the deformability of natural cell membranes much better than standard
      solid-supported lipid bilayers. 

PMID- 25046695
TI  - Effect of the fungus Pochonia chlamydosporia on Echinostoma paraensei (Trematoda:
      Echinostomatidae).
AB  - Echinostoma paraensei is a trematode of the genus Echinostoma that causes
      echinostomiasis in humans. The objectives of this study were to: evaluate the
      ovicidal activity of the nematophagous fungus Pochonia chlamydosporia (VC1 and
      VC4) on a solid medium 2% water-agar (2% WA) against E. paraensei eggs (assay A);
      evaluate ovicidal effect (destruction of eggs) of the isolate VC4 in supplemented
      culture media (assay B); and evaluate the ovicidal ability of the crude extract
      (VC4) on E. paraensei eggs (assay C). Eggs of E. paraensei (assay A) were placed
      in Petri dishes containing 2% WA with an isolate of the fungus P. chlamydosporia
      (VC1 and VC4) grown for 10 days, and without fungus as a control and evaluated
      regarding their destruction. In assay B, eggs of E. paraensei were placed in
      Petri dishes with different supplemented culture media and with VC4 isolate and
      the destruction of eggs was examined at the end of 25 days of interaction. In
      assay C, effects of the crude extract of P. chlamydosporia (VC4) on eggs were
      evaluated at the end of 7 days. In assay A, there was no difference (p>0.05) in
      ovicidal activity among the tested isolates (VC1 and VC4); however, the highest
      percentage for ovicidal activity (type 3 effect) was demonstrated by the isolate
      VC4. In assay B, the culture medium starch-agar showed the best results for the
      destruction of the eggs, with a percentage of 46.6% at the end of the assay. In
      assay C, the crude extract of VC4 was effective in the destruction of E.
      paraensei eggs, with a percentage reduction of 53%. The results of this study
      demonstrate that a rich culture medium with a greater availability of carbon and
      nitrogen may interfere directly in the predatory characteristics of ovicidal
      fungi. 

PMID- 25046696
TI  - Dog population management for the control of human echinococcosis.
AB  - Cystic and alveolar hydatid disease of humans caused by infection with
      Echinococcus granulosus or Echinococcus multilocularis are significant zoonoses
      in developing countries. For human infections, the main definitive host is the
      dog, and reduction in the population of unwanted dogs, together with anthelmintic
      treatment of wanted dogs, are recommended control procedures for these zoonoses.
      Both owned and unowned dogs have been shown to be a major source of Echinococcus
      spp. infection in developing countries. Unowned dogs are the most challenging
      category in dog population management for the control of major zoonotic diseases.
      Unowned dogs are those dogs that do not have an owner, and those dogs whose owner
      cannot readily be identified. Control of numbers of unowned dogs can be done in
      various ways if funds are available. Fertility control and humane euthanasia are
      likely to be the most effective procedures in developing countries. Fertility
      control requires significant funding, and where resources are scarce humane
      euthanasia may be the most effective option. Both procedures are ongoing events,
      with no predictable end point. This paper examines the sociology and technology
      for the population management of owned and unowned dogs, specifically for the
      reduction of human hydatid disease. Examples are given for developing and
      developed countries. Although a "One Health" approach is desirable, the
      technology for hydatid control is different from that for rabies, and FAO Animal
      Welfare recommendations for dog population management should be adjusted
      accordingly. 

PMID- 25046698
TI  - Elongation flow-triggered morphology transitions of dendritic polyethylene
      amphiphilic assemblies: host-guest implications.
AB  - The assemblies and transformations of dendritic polyethylene (DPE)
      poly(oligo(ethyleneglycol) methacrylate) (POEGMA) amphiphilic micelles have been
      demonstrated by cryo-TEM and DLS techniques under elongation flow stimuli. The
      flow rate-dependence of the dissymmetry ratio suggests the possibility that a
      combination of shear and elongation could also be responsible for the transitions
      of DPE-POEGMAs, but it is obvious that the exposure of elongation flow is
      essential and plays a key role in the assembly and fusion of the DPE-POEGMA
      micelles. Fluorescence resonance energy transfer (FRET) is used to provide
      insight into the assembly and fusion of DPE-POEGMA under elongation flow. The
      FRET results show that a shorter separation distance of DiO-DiI with higher
      elongation rate can result in higher FRET efficiency. Furthermore, DPE-POEGMAs
      can display the responsive switching ability of the elongation flow-triggered
      FRET. 

PMID- 25046697
TI  - Pure associative tactile agnosia for the left hand: clinical and anatomo
      functional correlations.
AB  - Associative tactile agnosia (TA) is defined as the inability to associate
      information about object sensory properties derived through tactile modality with
      previously acquired knowledge about object identity. The impairment is often
      described after a lesion involving the parietal cortex (Caselli, 1997; Platz,
      1996). We report the case of SA, a right-handed 61-year-old man affected by first
      ever right hemispheric hemorrhagic stroke. The neurological examination was
      normal, excluding major somaesthetic and motor impairment; a brain magnetic
      resonance imaging (MRI) confirmed the presence of a right subacute hemorrhagic
      lesion limited to the post-central and supra-marginal gyri. A comprehensive
      neuropsychological evaluation detected a selective inability to name objects when
      handled with the left hand in the absence of other cognitive deficits. A series
      of experiments were conducted in order to assess each stage of tactile
      recognition processing using the same stimulus sets: materials, 3D geometrical
      shapes, real objects and letters. SA and seven matched controls underwent the
      same experimental tasks during four sessions in consecutive days. Tactile
      discrimination, recognition, pantomime, drawing after haptic exploration out of
      vision and tactile-visual matching abilities were assessed. In addition, we
      looked for the presence of a supra-modal impairment of spatial perception and of
      specific difficulties in programming exploratory movements during recognition.
      Tactile discrimination was intact for all the stimuli tested. In contrast, SA was
      able neither to recognize nor to pantomime real objects manipulated with the left
      hand out of vision, while he identified them with the right hand without
      hesitations. Tactile-visual matching was intact. Furthermore, SA was able to
      grossly reproduce the global shape in drawings but failed to extract details of
      objects after left-hand manipulation, and he could not identify objects after
      looking at his own drawings. This case confirms the existence of selective
      associative TA as a left hand-specific deficit in recognizing objects. This
      deficit is not related to spatial perception or to the programming of exploratory
      movements. The cross-modal transfer of information via visual perception permits
      the activation of a partially degraded image, which alone does not allow the
      proper recognition of the initial tactile stimulus. 

PMID- 25046700
TI  - Detection of knockdown resistance mutations in the common bed bug, Cimex
      lectularius (Hemiptera: Cimicidae), in Australia.
AB  - BACKGROUND: Pyrethroid resistance in the common bed bug, Cimex lectularius L.,
      has been reported worldwide. An important resistance mechanism is via knockdown
      resistance (kdr) mutations, notably V419L and L925I. Information regarding this
      kdr-type resistance mechanism is unknown in Australia. This study aims to examine
      the status of kdr mutations in Australian C. lectularius strains. RESULTS:
      Several modern field-collected strains and museum-preserved reference collections
      of Australian C. lectularius were examined. Of the field strains (2007-2013), 96%
      had the known kdr mutations (L925I or both V419L/L925I). The 'Adelaide' strain
      (2013) and samples from the preserved reference collections (1994-2002) revealed
      no known kdr mutations. A novel mutation I936F was apparent in the insecticide
      resistant 'Adelaide' strain, one strain from Perth (with L925I) and the majority
      of the reference collection specimens. The laboratory insecticide-resistant
      'Sydney' strain showed a mixture of no kdr mutations (20%) and L925I (80%).
      CONCLUSION: The novel mutation I936F may be a kdr mutation but appeared to
      contribute less resistance to the pyrethroids than the V419L and L925I mutations.
      The detection of high frequencies of kdr mutations indicates that kdr-type
      resistance is widespread across Australia. Hence, there should be a reduced
      reliance on pyrethroid insecticides and an integrated management approach for the
      control of C. lectularius infestations.

PMID- 25046699
TI  - A 31-channel MR brain array coil compatible with positron emission tomography.
AB  - PURPOSE: Simultaneous acquisition of MR and positron emission tomography (PET)
      images requires the placement of the MR detection coil inside the PET detector
      ring where it absorbs and scatters photons. This constraint is the principal
      barrier to achieving optimum sensitivity on each modality. Here, we present a 31
      channel PET-compatible brain array coil with reduced attenuation but improved MR
      sensitivity. METHODS: A series of component tests were performed to identify
      tradeoffs between PET and MR performance. Aspects studied include the remote
      positioning of preamplifiers, coax size, coil trace size/material, and plastic
      housing. We then maximized PET performance at minimal cost to MR sensitivity. The
      coil was evaluated for MR performance (signal to noise ratio [SNR], g-factor) and
      PET attenuation. RESULTS: The coil design showed an improvement in attenuation by
      190% (average) compared with conventional 32-channel arrays, and no loss in MR
      SNR. Moreover, the 31-channel coil displayed an SNR improvement of 230% (cortical
      region of interest) compared with a PET-optimized 8-channel array with similar
      attenuation properties. Implementing attenuation correction of the 31-channel
      array successfully removed PET artifacts, which were comparable to those of the 8
      channel array. CONCLUSION: The design of the 31-channel PET-compatible coil
      enables higher sensitivity for PET/MR imaging, paving the way for novel
      applications in this hybrid-imaging domain.

PMID- 25046701
TI  - Feminism and psychology: critiques of methods and epistemology.
AB  - Starting in the 1960s, many of the critiques of psychological science offered by
      feminist psychologists focused on its methods and epistemology. This article
      evaluates the current state of psychological science in relation to this feminist
      critique. The analysis relies on sources that include the PsycINFO database, the
      Publication Manual of the American Psychological Association (American
      Psychological Association, 2010), and popular psychology methods textbooks. After
      situating the feminist critique within the late-20th-century shift of science
      from positivism to postpositivism, the inquiry examines feminists' claims of
      androcentric bias in (a) the underrepresentation of women as researchers and
      research participants and (b) researchers' practices in comparing women and men
      and describing their research findings. In most of these matters, psychology
      manifests considerable change in directions advocated by feminists. However,
      change is less apparent in relation to some feminists' criticisms of psychology's
      reliance on laboratory experimentation and quantitative methods. In fact, the
      analyses documented the rarity in high-citation journals of qualitative research
      that does not include quantification. Finally, the analysis frames feminist
      methodological critiques by a consideration of feminist epistemologies that
      challenge psychology's dominant postpositivism. Scrutiny of methods textbooks and
      journal content suggests that within psychological science, especially as
      practiced in the United States, these alternative epistemologies have not yet
      gained substantial influence.

PMID- 25046702
TI  - Protecting victims of violent patients while protecting confidentiality.
AB  - In this article I revisit Tarasoff v. Regents of the University of California
      (1976), a case decided by the California Supreme Court in 1976 and followed in
      whole or in part in approximately 33 U.S. jurisdictions. In Tarasoff, perhaps the
      most notorious case in mental health law, the court held that psychotherapists
      have a duty to protect intended victims of their patients' conduct if that
      conduct presents a serious danger of violence. The most prominent means of
      protection is to warn potential victims and law enforcement personnel. I argue
      that Tarasoff is bad law, bad social science, and bad social policy. Because of
      therapists' ethical obligation to disclose the limits of confidentiality at the
      beginning of treatment, informing patients of the therapist's duty to disclose
      threats may inhibit patients' expressions of violent urges. Alternatively, as in
      Tarasoff, once a threat of violence is disclosed, the patient may never return to
      therapy, making it impossible to work through the threat of violence. I argue
      that rather than mandate the breaching of confidentiality, it is sounder public
      policy to give therapists the discretion to disclose so that they may take other
      measures to protect potential victims. Finally, I briefly touch on the impact of
      cultural disparity between therapist and patient in these cases.

PMID- 25046703
TI  - Gold Medal Award for Life Achievement in the Application of Psychology.
AB  - The American Psychological Foundation (APF) Gold Medal Awards recognize
      distinguished and enduring records of accomplishment in four areas of psychology:
      the application of psychology, the practice of psychology, psychology in the
      public interest, and the science of psychology. The 2014 recipient of the Gold
      Medal Award for Life Achievement in the Application of Psychology is Richard M.
      Lerner.

PMID- 25046704
TI  - Gold Medal Award for Life Achievement in the Practice of Psychology.
AB  - The American Psychological Foundation (APF) Gold Medal Awards recognize
      distinguished and enduring records of accomplishment in four areas of psychology:
      the application of psychology, the practice of psychology, psychology in the
      public interest, and the science of psychology. The 2014 recipient of the Gold
      Medal Award for Life Achievement in the Practice of Psychology is Gilbert O.
      Sanders.

PMID- 25046705
TI  - Gold Medal Award for Life Achievement in Psychology in the Public Interest.
AB  - The American Psychological Foundation (APF) Gold Medal Awards recognize
      distinguished and enduring records of accomplishment in four areas of psychology:
      the application of psychology, the practice of psychology, psychology in the
      public interest, and the science of psychology. The 2014 recipient of the Gold
      Medal Award for Life Achievement in Psychology in the Public Interest is Bonnie
      R. Strickland.

PMID- 25046706
TI  - Gold Medal Award for Life Achievement in the Science of Psychology.
AB  - The American Psychological Foundation (APF) Gold Medal Awards recognize
      distinguished and enduring records of accomplishment in four areas of psychology:
      the application of psychology, the practice of psychology, psychology in the
      public interest, and the science of psychology. The 2014 recipient of the Gold
      Medal Award for Life Achievement in the Science of Psychology is Thomas J.
      Bouchard Jr.

PMID- 25046707
TI  - Charles L. Brewer Distinguished Teaching of Psychology Award.
AB  - The American Psychological Foundation (APF) Charles L. Brewer Award for
      Distinguished Teaching of Psychology recognizes an outstanding career
      contribution to the teaching of psychology. The 2014 recipient of the Charles L.
      Brewer Distinguished Teaching of Psychology Award is Mary E. Kite.

PMID- 25046709
TI  - APA guidelines: their importance and a plan to keep them current: 2013 annual
      report of the Policy and Planning Board.
AB  - When guidelines are approved by APA, they become association policy, and it is
      imperative that they remain current. The revision of guidelines poses several
      challenges to the association. These challenges range from the availability and
      allocation of resources to support the complicated processes involved in
      developing and updating these policies to the lack of a clearly defined process
      that includes identification of tasks, assignments of responsibilities, and so
      forth. For this reason, the APA Board of Directors asked the Policy and Planning
      Board (P&P) to work with the boards of the four directorates (i.e., the Education
      Directorate, the Practice Directorate, the Public Interest Directorate, and the
      Science Directorate) to create a proposal that would (a) make recommendations
      with regard to how the review and revision of guidelines documents might best be
      accomplished in accordance with the APA Strategic Plan and existing policies and
      procedures and (b) make suggestions regarding the association resources that
      might be required. The Board of Directors approved the proposed review process in
      December 2013.

PMID- 25046710
TI  - Report of the Ethics Committee, 2013.
AB  - In accordance with the bylaws of the American Psychological Association (APA),
      the Ethics Committee reports regularly to the membership regarding the number and
      types of ethics matters investigated and the major programs undertaken. In 2013,
      ethics adjudication, ethics education and consultation, and special projects were
      activities of the Ethics Committee.

PMID- 25046717
TI  - Julian B. Rotter (1916-2014).
AB  - One of the most influential psychologists of the 20th century, Julian B. Rotter,
      died at the age of 97 on January 6, 2014, at his home in Mansfield, Connecticut.
      Jules was born on October 22, 1916, in Brooklyn, New York, the third son of
      Jewish immigrant parents. As noted in the citation for his American Psychological
      Association (APA) Award for Distinguished Scientific Contributions, "his
      pioneering social learning framework...transformed behavioral approaches to
      personality and clinical psychology. He integrated the concepts of expectancy and
      reinforcement and built an enduring early bridge between the psychology of
      learning and its diverse social, clinical, and personality applications. His
      seminal studies of the variable of internal versus external locus of control
      provided the foundation for years of prolific research on choice and perceived
      control in several disciplines...Julian Rotter, by his writing, teaching, and
      personal example,...profoundly changed theory and practice in the field"
      (American Psychologist, 1989, p. 625). He was devoted to his family and shared
      his insights, his empathy, his compassion, and his admirable social conscience
      with them, as he did with his myriad friends and students.

PMID- 25046718
TI  - Milton Schwebel (1914-2013).
AB  - Milton Schwebel was born May 11, 1914, in Troy, New York, the son of Frank
      Schwebel and Sarah Oxenhandler Schwebel. He died October 3, 2013, in Tucson,
      Arizona. His 99 years were filled with love, activism, scholarship, and
      leadership. In educational psychology, he was a career-long proponent of
      educating disadvantaged children. A pioneer in peace psychology, Schwebel helped
      establish the field's intellectual foundation. Recognizing that politics, current
      events, and international affairs influenced children's mental and physical
      health. Over a remarkable 73-year publishing career, Schwebel's scholarly
      contributions included authoring, editing, or co-authoring 14 books and
      innumerable articles. Schwebel was always working to improve the human condition,
      and his scholarship was most prominent in three interwoven areas. Schwebel will
      long be remembered as a treasured friend and mentor who cared deeply about
      vulnerable people, particularly children, the underprivileged, and the
      disadvantaged. He enjoyed listening to diverse perspectives and was a renowned
      teacher, clinician, and lecturer, beloved by students and colleagues. His life
      serves as a beacon to all who seek to promote human well-being.

PMID- 25046719
TI  - George Chester Stone (1924-2013).
AB  - George Chester Stone was born February 21, 1924, and died on July 13, 2013. A
      quiet revolutionary, George was a founder of the field of health psychology.
      George played critical roles conceptualizing the field of health psychology,
      charting its bounds and potential, promulgating guidelines for training, founding
      the first doctoral program in health psychology, editing influential volumes
      defining the new field, launching the flagship journal for the field, and
      establishing a home for the field within APA. He was able to accomplish all this
      through his talent for working collaboratively.

PMID- 25046720
TI  - David L. Gutmann (1925-2013).
AB  - David L. Gutmann, a pioneer in geropsychology and professor emeritus at
      Northwestern University, died on November 3, 2013, at the age of 88. A student of
      Bernice Neugarten, Bruno Bettelheim, and Erik Erikson, Gutmann discovered changes
      in adult psychological development related to parenting styles that held across
      diverse cultures.

PMID- 25046721
TI  - Joyce Brothers (1927-2013).
AB  - Joyce Brothers died May 13, 2013, at age 85, in Fort Lee, New Jersey. She was
      born in Brooklyn, New York, on October 20, 1927. To the public, Joyce Brothers
      was the best known psychologist of her time. Brothers's influence on the media,
      and psychology, was considerable and varied. She became the public face of
      psychology. As her ascendency as a media psychologist progressed, she reinforced
      the ideas that a PhD psychologist is called "Doctor"; that a woman can create a
      career in the field and also raise a family; that there are psychological
      insights about human behavior that everyone can understand; and that
      psychologists are not always wearing laboratory coats or talking to people who
      lie on a couch, but can be lively, engaging, understandable, fun, and down-to
      earth people. One might speculate that Joyce Brothers brought a lot of young
      women into careers in psychology. Brothers created an amazing career which she
      pursued with style and grace. Stepping outside of a traditional psychological
      career sometimes drew fire from the profession, in line with frequent criticism
      of popularizers in psychology and other fields.

PMID- 25046722
TI  - Nathan Kogan (1927-2013).
AB  - Nathan Kogan, professor emeritus of psychology at the New School for Social
      Research and visiting scholar at the Educational Testing Service (ETS), died on
      April 28, 2013, in Princeton, New Jersey, at the age of 86. The son of immigrants
      from Poland and Ukraine, Nat was born in Bethlehem, Pennsylvania, on May 2, 1926.
      Nat described himself as a general psychologist, an apt characterization given
      the remarkable breadth of his research spanning cognitive, personality, social,
      developmental, and, most recently, evolutionary psychology. He was an unusually
      modest man, a conscientious collaborator, and a dedicated mentor to generations
      of graduate students, junior faculty, and young researchers. A prodigious
      researcher and a prolific writer (with more than 100 articles and chapters and
      several books to his credit), he was active until the very end.

PMID- 25046723
TI  - Theodore Millon (1928-2014).
AB  - Theodore Millon was born on August 18, 1928. On January 29, 2014, Ted died
      peacefully in his sleep of congestive heart failure. Ted was a scholar and
      prolific writer. He penned--literally, since he never used a keyboard--and edited
      more than 30 books and authored or co-authored more than 100 book chapters and
      research articles. Ted may be most recognizable for the family of objective
      inventories that bear his name. His development of the Millon Clinical Multiaxial
      Inventory in the 1970s revolutionized personality assessment here and abroad.
      Over time, many new instruments were developed that targeted adolescent (MAPI,
      MACI), preadolescent (M-PACI), medical (MBMD), college (MCCI), and normal (MIPS)
      populations. Beginning in 2004, Ted funded the American Psychological
      Foundation's annual award, given in his name, honoring an outstanding
      psychologist engaged in advancing the science of personality psychology.

PMID- 25046724
TI  - Alan S. Gurman (1945-2013).
AB  - Alan S. Gurman, one of the most distinguished and influential family
      psychologists of our day, was born in Winthrop, Massachusetts, May 26, 1945, and
      died in Madison, Wisconsin, September 6, 2013. The consummate editor and author,
      Al held many editorial posts. Al can be credited with moving couple and family
      therapy from a collection of approaches to a field of study. He pioneered
      bringing science to practice and in doing so brought credibility to couple and
      family therapy to those outside the field.

PMID- 25046727
TI  - 2013 Annual Report of the American Psychological Association.

PMID- 25046728
TI  - 3D-printed haptic "reverse" models for preoperative planning in soft tissue
      reconstruction: a case report.
AB  - In reconstructive surgery, preoperative planning is essential for optimal
      functional and aesthetic outcome. Creating a three-dimensional (3D) model from
      two-dimensional (2D) imaging data by rapid prototyping has been used in
      industrial design for decades but has only recently been introduced for medical
      application. 3D printing is one such technique that is fast, convenient, and
      relatively affordable. In this report, we present a case in which a reproducible
      method for producing a 3D-printed "reverse model" representing a skin wound
      defect was used for flap design and harvesting. This comprised a 82-year-old man
      with an exposed ankle prosthesis after serial soft tissue debridements for wound
      infection. Soft tissue coverage and dead-space filling were planned with a
      composite radial forearm free flap (RFFF). Computed tomographic angiography (CTA)
      of the donor site (left forearm), recipient site (right ankle), and the left
      ankle was performed. 2D data from the CTA was 3D-reconstructed using computer
      software, with a 3D image of the left ankle used as a "control." A 3D model was
      created by superimposing the left and right ankle images, to create a "reverse
      image" of the defect, and printed using a 3D printer. The RFFF was thus planned
      and executed effectively, without complication. To our knowledge, this is the
      first report of a mechanism of calculating a soft tissue wound defect and
      producing a 3D model that may be useful for surgical planning. 3D printing and
      particularly "reverse" modeling may be versatile options in reconstructive
      planning, and have the potential for broad application.

PMID- 25046729
TI  - Wolbachia endosymbionts and human disease control.
AB  - Most human filarial nematode parasites and arthropods are hosts for a bacterial
      endosymbiont, Wolbachia. In filaria, Wolbachia are required for normal
      development, fertility and survival, whereas in arthropods, they are largely
      parasitic and can influence development and reproduction, but are generally not
      required for host survival. Due to their obligate nature in filarial parasites,
      Wolbachia have been a target for drug discovery initiatives using several
      approaches including diversity and focused library screening and genomic sequence
      analysis. In vitro and in vivo anti-Wolbachia antibiotic treatments have been
      shown to have adulticidal activity, a long sought goal of filarial parasite drug
      discovery. In mosquitoes, it has been shown that the presence of Wolbachia can
      inhibit the transmission of certain viruses, such as Dengue, Chikungunya, Yellow
      Fever, West Nile, as well as the infectivity of the malaria-causing protozoan,
      Plasmodium and filarial nematodes. Furthermore, Wolbachia can cause a form of
      conditional sterility that can be used to suppress populations of mosquitoes and
      additional medically important insects. Thus Wolbachia, a pandemic endosymbiont
      offers great potential for elimination of a wide-variety of devastating human
      diseases. 

PMID- 25046730
TI  - Soft gel capsules improve melatonin's bioavailability in humans.
AB  - OBJECTIVE: Oral bioavailability is one of the most important properties in drug
      design and development. A poor oral bioavailability can result in low efficacy
      and unpredictable response to a drug. Several dosages of melatonin have been used
      for various investigations to clarify its bioavailability in humans. Aiming to
      search for a pharmaceutical form, which is better absorbed, the pharmacokinetic
      (PK) profile of the new manufactured melatonin soft gelatin (soft gel) capsule
      form has been evaluated and compared with the commercially available melatonin
      powder. RESEARCH DESIGN AND METHODS: A total of 60 healthy volunteers received 1,
      3 mg of melatonin powder and 1 mg of melatonin in soft gel capsules. PK profiles
      were obtained by analysis of melatonin plasma concentration, and the respective
      melatonin bioavailability was compared. RESULTS: Melatonin soft gel capsule form
      showed similar PK parameters compared with the highest doses of melatonin in
      powder form, but its bioavailability was improved. CONCLUSIONS: Soft gel capsules
      improved the bioavailability of melatonin in humans even when administered dose
      was reduced. Considering the number of conditions in which melatonin
      supplementation is recommended, this evidence could support a broader use of
      melatonin in clinical practice.

PMID- 25046731
TI  - Developmental antecedents of abnormal eating attitudes and behaviors in
      adolescence.
AB  - OBJECTIVE: This study capitalizes on developmental data from an Australian
      population-based birth cohort to identify developmental markers of abnormal
      eating attitudes and behaviors in adolescence. The aims were twofold: (1) to
      develop a comprehensive path model identifying infant and childhood developmental
      correlates of Abnormal Eating Attitudes and Behaviors in adolescence, and (2) to
      explore potential gender differences. METHOD: Data were drawn from a 30-year
      longitudinal study that has followed the health and development of a population
      based cohort across 15 waves of data collection from infancy since 1983: The
      Australian Temperament Project. Participants in this analysis were the 1,300
      youth who completed the 11th survey at 15-16 years (1998) and who completed the
      eating disorder inventory at this time point. RESULTS: Developmental correlates
      of Abnormal Eating Attitudes and Behaviors in mid-adolescence were temperamental
      persistence, early gestational age, persistent high weight, teen depression,
      stronger peer relationships, maternal dieting behavior, and pubertal timing.
      Overall, these factors accounted for 28% of the variance in Abnormal Eating
      Attitudes and Behaviors at 15-16 years of age. Depressive symptoms, maternal
      dieting behavior, and early puberty were more important factors for girls. Late
      puberty was a more important factor for boys. DISCUSSION: Findings address an
      important gap in our understanding of the etiology of Abnormal Eating Attitudes
      and Behaviors in adolescence and suggest multiple targets for preventive
      intervention.

PMID- 25046732
TI  - Germanium coating boosts lithium uptake in Si nanotube battery anodes.
AB  - Si nanotubes for reversible alloying reaction with lithium are able to
      accommodate large volume changes and offer improved cycle retention and reliable
      response when incorporated into battery anodes. However, Si nanotube electrodes
      exhibit poor rate capability because of their inherently low electron
      conductivity and Li ion diffusivity. Si/Ge double-layered nanotube electrodes
      show promise to improve structural stability and electrochemical kinetics, as
      compared to homogeneous Si nanotube arrays. The mechanism explaining the
      enhancement in the rate capabilities is revealed here by means of electrochemical
      impedance methods. The Ge shell efficiently provides electrons to the active
      materials, which increase the semiconductor conductivity thereby assisting Li(+)
      ion incorporation. The charge transfer resistance which accounts for the
      interfacial Li(+) ion intake from the electrolyte is reduced by two orders of
      magnitude, indicating the key role of the Ge layer as an electron supplier. Other
      resistive processes hindering the electrode charge-discharge process are observed
      to show comparable values for Si and Si/Ge array electrodes. 

PMID- 25046733
TI  - Degradable, antibiotic releasing poly(propylene fumarate)-based constructs for
      craniofacial space maintenance applications.
AB  - Space maintainers (SMs) used for craniofacial reconstruction function to preserve
      the void space created upon bone loss and promote soft tissue healing over the
      defect. Polymethylmethacrylate-based SMs present several drawbacks including
      implant exposure, secondary removal surgeries, and potential bacterial
      contamination during implantation. To address these issues, a novel composite
      material comprising poly(propylene fumarate) (PPF) with N-vinyl pyrrolidone (NVP)
      as the crosslinking agent, carboxymethylcellulose (CMC) hydrogel as a porogen,
      and antibiotic loaded poly(lactic-co-glycolic acid) (PLGA) microparticles as
      antibiotic carriers and porogen was fabricated. CMC was incorporated at 40 wt %
      to impart rapid porosity while PLGA microparticles were incorporated at 30 or 40
      wt % to release either clindamycin or colistin. This study was designed to
      examine the effects of PPF:NVP ratio, PLGA wt %, and the drug dose on the mass
      loss, temporal porosity change and drug release kinetics of the composite
      construct. Mass loss decreased significantly in constructs containing 3:2 PPF:NVP
      ratio with 30 wt % PLGA (63.2 +/- 0.8%) compared to the 2:3 PPF:NVP ratio (80.3
      +/- 1.0% and 85.3 +/- 1.3% for 30 and 40 wt % PLGA content, respectively) at 8
      weeks. In formulations with 3:2 PPF:NVP ratio, incorporation of 40 versus 30 wt %
      PLGA significantly increased the porosity at 8 weeks under accelerated
      degradation conditions. Constructs released clindamycin or colistin at
      concentrations above the minimum inhibitory concentration for target pathogens
      for 45 and 77 days, respectively. This study demonstrates that the composition of
      PPF/CMC/PLGA constructs can be modulated to achieve properties suitable for
      craniofacial degradable space maintenance applications.

PMID- 25046734
TI  - Calmodulin dependent protein kinase II activation by exercise regulates saturated
      & unsaturated fatty acids and improves some metabolic syndrome markers.
AB  - AIMS: Activation of Calmodulin dependent protein kinase (CaMK)-II by exercise has
      a plethora of benefits in health. Fatty acids play a pivotal role in the
      pathogenesis of metabolic syndrome (MetS). Prevention of MetS and treatment of
      its main characteristics are very significant to fight against type 2 diabetes.
      CaMKII activation in the regulation of saturated and unsaturated fatty acids in
      relation to type 2 diabetes and MetS has not been studied, which became the focus
      of this present study. MAIN METHODS: Using Gas chromatography-Mass spectrometry,
      we investigated saturated fatty acids and unsaturated fatty acids. Quantitative
      real time PCR was also used to assess the gene expression. KEY FINDINGS: Results
      indicate that both palmitoleic acid and oleic acid which are monounsaturated
      fatty acids were increased in response to CaMKII activation. On the other hand,
      myristic acid and palmitic acid which are saturated fatty acids known to increase
      the risk factors of MetS and type 2 diabetes were decreased by exercise induction
      of CaMKII. Conversely, lauric acid also a saturated fatty acid was increased in
      response to CaMKII activation by exercise. This fatty acid is known to have
      beneficial effects in alleviating symptoms of both type 2 diabetes and MetS.
      SIGNIFICANCE: According to our knowledge, this is the first study to show that
      CaMKII activation by exercise regulates fatty acids essential in type 2 diabetes
      and MetS. CaMKII can be an avenue of designing novel therapeutic drugs in the
      management and treatment of type 2 diabetes and MetS.

PMID- 25046735
TI  - Endogenous ACh suppresses LTD induction and nicotine relieves the suppression via
      different nicotinic ACh receptor subtypes in the mouse hippocampus.
AB  - AIMS: Studying the normal role of nicotinic cholinergic systems in hippocampal
      synaptic plasticity is critical for understanding how cholinergic loss in
      Alzheimer's disease (AD) and tobacco use affect cognitive function. However, it
      is largely unknown how nicotinic cholinergic systems regulate the induction of
      long-term depression (LTD). MAIN METHODS: Extracellular field potential
      recordings were performed in hippocampal slices prepared from wild-type, alpha2,
      alpha7, and beta2 knockout (KO) mice. Effects of nicotine and nicotinic
      antagonists on LTD induction in wild-type, alpha2, alpha7, and beta2 KO mice were
      compared. KEY FINDINGS: Activation of alpha7 nicotinic acetylcholine receptors
      (nAChRs) occurs during LTD-inducing stimulation to suppress LTD induction at CA3
      CA1 synapses. Nicotine relieves this suppression, causing larger LTD. This
      nicotine effect was mediated by the activation of non-alpha7 nAChR subtypes,
      which were not activated by ACh released during LTD-inducing stimulation, and
      requires the presence of endogenous ACh-induced alpha7 nAChR activation.
      Furthermore, the effect of nicotine was prevented in the presence of
      mecamylamine, but not dihydro-beta-erythroidine, and was still observed in both
      alpha2 KO and beta2 KO mice. SIGNIFICANCE: This is the first report to evaluate
      the involvement of different nAChR subtypes in LTD induction. Findings indicate
      the involvement of unique non-alpha7 nAChR subtypes, which have not been
      considered in the nicotinic modulation of hippocampal long-term potentiation, in
      the control of LTD induction. The implication of our results is that the loss of
      cholinergic projections to the hippocampus, which reduces ACh release as seen in
      AD patients, and nicotine from tobacco smoking can differentially affect LTD
      induction.

PMID- 25046737
TI  - Effects of exposure to high concentrations of waterborne Tl on K and Tl
      concentrations in Chironomus riparius larvae.
AB  - Thallium (Tl) is a non-essential metal which is released into the environment
      primarily as the result of anthropogenic activities such as fossil fuel burning
      and smelting of ores. The ionic radius of monovalent Tl+ is similar to that of K+
      and Tl+ may thus interfere with K+-dependent processes. We determined that the
      acute (48 h) lethal concentration where 50% of the organisms do not survive
      (LC50) of Tl for 4th instar Chironomus riparius larvae was 723 MUmol L-1.
      Accumulation of Tl by the whole animal was saturable, with a maximum accumulation
      (Jmax) of 4637 MUmol kg-1 wet mass, and K(D) of 670 MUmol Tl l-1. Tl accumulation
      by the gut appeared saturable at the lowest four Tl concentrations, with a Jmax
      of 2560 MUmol kg-1 wet mass and a K(D) of 54.5 MUmol Tl l-1. The saturable
      accumulation at the gut may be indicative of a limited capacity for intracellular
      detoxification, such as storage in lysosomes or complexation with metal-binding
      proteins. Tl accumulation by the hemolymph was found to be linear and Tl
      concentrations in the hemolymph were ~75% of the exposure concentration at Tl
      exposures >26.9 MUmol L-1. There was not a significant decrease in whole animal,
      gut or hemolymph K during exposure to waterborne Tl at any of the concentrations
      tested (up to 1500 MUmol L-1). The avoidance of hypokalemia by C. riparius larvae
      may contribute to survival during acute waterborne exposures to Tl.

PMID- 25046738
TI  - Attention bias modification (ABM) as a treatment for child and adolescent
      anxiety: a systematic review.
AB  - BACKGROUND: Attention Bias Modification (ABM) is a novel computer based treatment
      for anxiety disorders. It has been proposed as an efficient, accessible
      psychological therapy and is based on cognitive theories of attention. The
      present review sought to investigate the efficacy of ABM as a potential treatment
      for child and adolescent anxiety. METHOD: A systematic literature review was
      conducted, using three main databases, PsycINFO, Embase and Medline, to identify
      original research articles which measured the effect of ABM on anxiety levels in
      children and/or adolescents. RESULTS: Ten articles met the inclusion criteria and
      of these 10, three were randomised control trials. A lack of standardisation in
      relation to the treatment protocol was observed; nonetheless the identified
      studies generally provided evidence for the efficacy of ABM as an anxiety
      treatment. LIMITATIONS: Due to the nature of the studies found, a statistical
      meta-analysis was not possible. CONCLUSIONS: ABM seems to be a promising, novel
      treatment for child and/or adolescent anxiety disorders with merits over
      lengthier, talking based therapies. However, more rigorous research trials are
      needed to clarify the mechanisms behind ABM and establish effective, standardised
      treatment protocols.

PMID- 25046739
TI  - Efficacy of olanzapine in the treatment of bipolar mania with mixed features
      defined by DSM-5.
AB  - BACKGROUND: These analyses compared efficacy of olanzapine in patients with
      bipolar mania with or without mixed features, as defined in the DSM-5. METHODS:
      Pooled data from 3 placebo-controlled olanzapine studies in patients having
      bipolar I disorder with manic/mixed episode were analyzed (N=228 olanzapine;
      N=219 placebo). Patients were categorized for mixed features by number of
      concurrent depressive symptoms at baseline (0, 1, and 2 [category A; without
      mixed features], and >=3 [category B; with mixed features]), as determined by HAM
      D17 item score >=1. Depressive symptoms corresponded to 6 HAM-D17 items in the
      DSM-5 definition of manic episode with mixed features. Primary efficacy was
      evaluated by changes in the baseline-to-3-week YMRS total score. RESULTS:
      Patients were categorized into A (N=322; 72.0%) or B (N=125; 28.0%). Mean
      baseline YMRS total scores were 28.1 in category A and 27.8 in category B. Least
      squares mean change of YMRS total scores in categories A and B (olanzapine versus
      placebo) were -11.78 versus -6.86 and -13.21 versus -4.72, respectively. Patients
      in the olanzapine- compared with placebo-group experienced a greater decrease in
      YMRS total score for both categories (p<0.001). An interaction between mixed
      features and treatment was seen in YMRS change at a 0.3 significance level
      (p=0.175). LIMITATIONS: The results are from post-hoc analyses. CONCLUSIONS:
      Olanzapine was efficacious in the treatment of bipolar I mania, in patients both
      with and without mixed features, defined by DSM-5; however, greater efficacy was
      observed in patients with mixed features having more severe depressive symptoms.

PMID- 25046740
TI  - Darwinian depression.
AB  - BACKGROUND: The standard evolutionary explanation for depression is that being in
      an emotionally depressed state is adaptive. METHOD: The article first undertakes
      a critical review of the extant literature. It then provides an alternative
      evolutionary explanation for event-based depression and elation. It argues that
      being in a depressed state is not adaptive (indeed, quite the opposite), but that
      the threat of depression for bad outcomes and the promise of pleasure for good
      outcomes are adaptive because they motivate the individual toward undertaking
      effort that increases fitness. The article then explains reasons for failure in
      the motivation system and the mood disorders that arise as a consequence.
      RESULTS: The article explains why motivation depends on both elation and
      depression and why individual happiness is not permanently improved by winning
      the lottery (or permanently reduced by becoming wheelchair bound). It explains
      the comorbidity of bipolar disorder and panic disorder, why mood stabilizers tend
      to reduce motivation, and when anti-depressants are unlikely to cure "laziness."
      LIMITATIONS: The evolutionary explanation for depression does not directly
      provide clinical criteria for determining when major depressive disorder is
      present nor has it yet provided new treatment strategies for mood disorders.
      CONCLUSIONS: The theory presented here provides a coherent explanation for
      depression and elation and leads research in a different direction from previous
      evolutionary explanations.

PMID- 25046741
TI  - Bipolar disorder in adults with Asperger's Syndrome: a systematic review.
AB  - BACKGROUND: Asperger's Syndrome (AS) is a neurodevelopmental disorder included in
      the Autism Spectrum (ASD). The current literature shows growing evidence of a
      high rate of comorbidity between AS and other psychiatric disorders, particularly
      Bipolar Disorder (BD). We reviewed available epidemiological and clinical data on
      BD-AS comorbidity and its diagnostic and therapeutic implications METHODS: A
      systematic review of the literature was conducted through PubMed, Scopus and
      Psych-Info using combinations of the following search terms: Asperger's Syndrome,
      Bipolar Disorder, depression, mood disorder, psychiatric comorbidity, treatment,
      mood stabilizers, anticonvulsants, antipsychotics, and antidepressants. RESULTS:
      BD prevalence in adults with AS ranges from 6% to 21.4% of the cases. Relatives
      of patients with AS showed a doubled risk of being affected by BD and a BD
      prevalence near to 10%. When comorbid with AS, BD assumes peculiar features which
      might shape its under-recognition or misdiagnosis (especially schizophrenia when
      psychotic symptoms are prominent). Although controlled data on pharmacological
      treatments in BD-AS comorbidity are substantially lacking, information is derived
      by open observations, case series and chart reviews. Mood stabilizers should be
      considered the first choice, and antipsychotics, especially second generation
      drugs (SGA) with 5-HT2a antagonism, have been shown useful in controlling
      psychotic and behavioral symptoms and improving social withdrawal. Some evidence
      of efficacy for the treatment of anxiety, obsessive-compulsive symptoms and
      depression is reported for SSRI antidepressants. The use of these drugs should be
      carefully monitored, because activation with hypomanic or manic switches is
      reported up to 54% of the treated subjects. CONCLUSION: BD in AS patients is
      frequent, usually it onsets during adolescence and is often characterized by
      atypical presentation, making its correct identification particularly difficult.
      A correct diagnosis of BD in AS individuals has relevant implications on the
      choice of adequate psychopharmacological, psycho-social and rehabilitative
      treatments.

PMID- 25046742
TI  - In vitro evaluation of the probiotic and functional potential of Lactobacillus
      strains isolated from fermented food and human intestine.
AB  - This study aims to evaluate the functional and probiotic characteristics of eight
      indigenous Lactobacillus strains in vitro. The selected lactobacilli include
      strains of Lactobacillus casei subsp. casei, Lactobacillus salivarius subsp.
      salicinius, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus
      delbrueckii subsp. lactis, Lactobacillus delbrueckii subsp. bulgaricus, and
      Lactobacillus rhamnosus. All strains tolerated both pH 2 for 3 h and 1% bile salt
      for 24 h. The strains CICC 23174 and CGMCC 1.557 were the most adhesive strains
      producing the highest quantity of EPS. Although a wide variation in the ability
      of the eight strains to deplete cholesterol and nitrite, antagonize pathogens,
      scavenge free radical, and stimulate innate immune response were observed, the
      strains CICC 23174 and CGMCC 1.557 showed the widest range of these useful
      traits. Taken together, the strains CICC 23174 and CGMCC 1.557 exhibited the best
      probiotic properties with the potential for use in the production of probiotic
      fermented foods. 

PMID- 25046743
TI  - A pilot study of cerebrovascular reactivity autoregulation after pediatric
      cardiac arrest.
AB  - AIM: Improved survival after cardiac arrest has placed greater emphasis on
      neurologic resuscitation. The purpose of this pilot study was to evaluate the
      relationship between cerebrovascular autoregulation and neurologic outcomes after
      pediatric cardiac arrest. METHODS: Children resuscitated from cardiac arrest had
      autoregulation monitoring during the first 72h after return of circulation with
      an index derived from near-infrared spectroscopy in a pilot study. The range of
      mean arterial blood pressure (MAP) with optimal vasoreactivity (MAPOPT) was
      identified. The area under the curve (AUC) of the time spent with MAP below
      MAPOPT and MAP deviation below MAPOPT was calculated. Neurologic outcome measures
      included placement of a new tracheostomy or gastrostomy, death from a primary
      neurologic etiology (brain death or withdrawal of support for neurologic
      futility), and change in the Pediatric Cerebral Performance Category score
      (DeltaPCPC). RESULTS: Thirty-six children were monitored. Among children who did
      not require extracorporeal membrane oxygenation (ECMO), children who received a
      tracheostomy/gastrostomy had greater AUC during the second 24h after
      resuscitation than those who did not (P=0.04; n=19). Children without ECMO who
      died from a neurologic etiology had greater AUC during the first 48h than did
      those who lived or died from cardiovascular failure (P=0.04; n=19). AUC below
      MAPOPT was not associated with DeltaPCPC when children with or without ECMO were
      analyzed separately. CONCLUSIONS: Deviation from the blood pressure with optimal
      autoregulatory vasoreactivity may predict poor neurologic outcomes after
      pediatric cardiac arrest. This experimental autoregulation monitoring technique
      may help individualize blood pressure management goals after resuscitation.

PMID- 25046744
TI  - Benefits of simulation based training for neonatal resuscitation education: a
      systematic review.
AB  - BACKGROUND: Simulation-based training (SBT) is being more frequently recommended
      for neonatal resuscitation education (NRE). It is important to assess if SBT
      improves clinical outcomes as neonatal resuscitation aims to improve survival
      without long-term neurodevelopmental impairment. We aimed to assess the evidence
      supporting benefits of SBT in NRE. METHOD: A systematic review was conducted
      using the Cochrane methodology. PubMed, Embase, PsycInfo and Cochrane databases
      were searched. Related abstracts were scanned and full texts of the potentially
      relevant articles were studied. Randomised controlled trials (RCT) and quasi
      experimental studies with controls (non-RCT) assessing SBT for NRE were eligible
      for inclusion in the review. RESULTS: Four small studies [three RCT (n=126) and
      one non-RCT (n=60)] evaluated SBT for NRE. Participants included medical students
      (one RCT and one non-RCT), residents (one RCT) and nursing staff (one RCT).
      Outcomes included performance in a simulation scenario, theoretical knowledge,
      and confidence in leading a resuscitation scenario. One RCT favoured simulation
      [improved resuscitation score (p=0.016), 2.31 more number of critical actions
      (p=0.017) and decreased time to achieve resuscitation steps (p=<0.001)]. The
      remaining two RCTs and the non-RCT did not find any difference between SBT and
      alternate methods of instruction. None of the four studies reported clinical
      outcomes. CONCLUSIONS: Evidence regarding benefits of SBT for NRE is limited.
      There are no data on clinical outcomes following SBT for NRE. Large RCTs
      assessing clinically important outcomes are required before SBT can be
      recommended widely for NRE.

PMID- 25046745
TI  - Study on the characteristics of gas molecular mean free pathin nanopores by
      molecular dynamics simulations.
AB  - This paper presents studies on the characteristics of gas molecular mean freepath
      in nanopores by molecular dynamics simulation. Our study results indicate that
      themean free path of all molecules in nanopores depend on both the radius of the
      nanoporeand the gas-solid interaction strength. Besides mean free path of all
      molecules in thenanopore, this paper highlights the gas molecular mean free path
      at different positions ofthe nanopore and the anisotropy of the gas molecular
      mean free path at nanopores. Themolecular mean free path varies with the
      molecule's distance from the center of thenanopore. The least value of the mean
      free path occurs at the wall surface of the nanopore.The present paper found that
      the gas molecular mean free path is anisotropic when gas isconfined in nanopores.
      The radial gas molecular mean free path is much smaller than themean free path
      including all molecular collisions occuring in three directions. Our studyresults
      also indicate that when gas is confined in nanopores the gas molecule number
      densitydoes not affect the gas molecular mean free path in the same way as it
      does for the gas inunbounded space. These study results may bring new insights
      into understanding the gasflow's characteristic at nanoscale. 

PMID- 25046746
TI  - A novel feature extraction scheme with ensemble coding for protein-protein
      interaction prediction.
AB  - Protein-protein interactions (PPIs) play key roles in most cellular processes,
      such as cell metabolism, immune response, endocrine function, DNA replication,
      and transcription regulation. PPI prediction is one of the most challenging
      problems in functional genomics. Although PPI data have been increasing because
      of the development of high-throughput technologies and computational methods,
      many problems are still far from being solved. In this study, a novel predictor
      was designed by using the Random Forest (RF) algorithm with the ensemble coding
      (EC) method. To reduce computational time, a feature selection method (DX) was
      adopted to rank the features and search the optimal feature combination. The DXEC
      method integrates many features and physicochemical/biochemical properties to
      predict PPIs. On the Gold Yeast dataset, the DXEC method achieves 67.2% overall
      precision, 80.74% recall, and 70.67% accuracy. On the Silver Yeast dataset, the
      DXEC method achieves 76.93% precision, 77.98% recall, and 77.27% accuracy. On the
      human dataset, the prediction accuracy reaches 80% for the DXEC-RF method. We
      extended the experiment to a bigger and more realistic dataset that maintains 50%
      recall on the Yeast All dataset and 80% recall on the Human All dataset. These
      results show that the DXEC method is suitable for performing PPI prediction. The
      prediction service of the DXEC-RF classifier is available at
      http://ailab.ahu.edu.cn:8087/ DXECPPI/index.jsp. 

PMID- 25046747
TI  - S-(-)-10,11-dihydroxyfarnesoic acid methyl ester inhibits melanin synthesis in
      murine melanocyte cells.
AB  - The development of antimelanogenic agents is important for the prevention of
      serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas.
      In the course of screening for melanin synthesis inhibitors, we found that the
      culture broth from an insect morphopathogenic fungus, Beauveria bassiana CS1029,
      exhibits potent antimelanogenic activity. We isolated and purified an active
      metabolite and identified it as S-(-)-10,11-dihydroxyfarnesoic acid methyl ester
      (dhFAME), an insect juvenile hormone. To address whether dhFAME inhibits melanin
      synthesis, we first measured the size of the melanin biosynthesis inhibition zone
      caused by dhFAME. dhFAME also showed inhibitory activity against mushroom
      tyrosinase in Melan-a cells. Intracellular, dose-dependent tyrosinase inhibition
      activity was also confirmed by zymography. In addition, we showed that dhFAME
      strongly inhibits melanin synthesis in Melan-a cells. Furthermore, we compared
      levels of TYR, TRP-1, TRP-2, MITF, and MC1R mRNA expression by reverse
      transcription polymerase chain reaction and showed that treatment of Melan-a
      cells with 35 MUM dhFAME led to an 11-fold decrease in TYR expression, a 6-fold
      decrease in TRP-2 expression, and a 5-fold decrease in MITF expression. Together,
      these results indicate that dhFAME is a potent inhibitor of melanin synthesis
      that can potentially be used for cosmetic biomaterial(s). 

PMID- 25046748
TI  - Clinical significance of POU5F1P1 rs10505477 polymorphism in Chinese gastric
      cancer patients receving cisplatin-based chemotherapy after surgical resection.
AB  - This study aimed to investigate the association between POU class5 homeobox 1
      pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese
      gastric cancer patients, who received cisplatin-based chemotherapy after surgical
      resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944
      gastric cancer patients who received gastrectomy. The association of rs10505477
      G>A polymorphism with the progression and prognosis in gastric cancer patients
      was statistically analyzed using the SPSS version 18.0 for Windows. The results
      reveal that rs10505477 polymorphism has a negatively effect on the overall
      survival of gastric cancer patients in cisplatin-based chemotherapy subgroup
      (HR=1.764, 95% CI=1.069-2.911, p=0.023). Our preliminary study indicates for the
      first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer
      patients who receving cisplatin-based chemotherapy after gastrectomy. Further
      studies are warranted to investigate the mechanism and to verify our results in
      different populations.

PMID- 25046749
TI  - Cordycepin down-regulates multiple drug resistant (MDR)/HIF-1alpha through
      regulating AMPK/mTORC1 signaling in GBC-SD gallbladder cancer cells.
AB  - Gallbladder cancer is the most common malignancy of the bile duct, with low 5
      year survival rate and poor prognosis. Novel effective treatments are urgently
      needed for the therapy of this disease. Here, we showed that cordycepin, the
      bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in
      cultured gallbladder cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines). We found
      that cordycepin inhibited mTOR complex 1 (mTORC1) activation and down-regulated
      multiple drug resistant (MDR)/hypoxia-inducible factor 1alpha (HIF-1alpha)
      expression through activating of AMP-activated protein kinase (AMPK) signaling in
      gallbladder cancer GBC-SD cells. Contrarily, AMPKalpha1-shRNA depletion
      dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD
      cell apoptosis. Further, our results showed that co-treatment with a low
      concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD
      cells to gemcitabine and 5-fluorouracil (5-FU), and the mechanism may be
      attributed to AMPK activation and MDR degradation. In summary, cordycepin induces
      growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK
      signaling. Cordycepin could be a promising new drug or chemo-adjuvant for
      gallbladder cancer. 

PMID- 25046750
TI  - Antibacterial effect of dental adhesive containing dimethylaminododecyl
      methacrylate on the development of Streptococcus mutans biofilm.
AB  - Antibacterial bonding agents and composites containing dimethylaminododecyl
      methacrylate (DMADDM) have been recently developed. The objectives of this study
      were to investigate the antibacterial effect of novel adhesives containing
      different mass fractions of DMADDM on Streptococcus mutans (S. mutans) biofilm at
      different developmental stages. Different mass fractions of DMADDM were
      incorporated into adhesives and S. mutans biofilm at different developmetal
      stages were analyzed by MTT assays, lactic acid measurement, confocal laser
      scanning microscopy and scanning electron microscopy observations.
      Exopolysaccharides (EPS) staining was used to analyze the inhibitory effect of
      DMADDM on the biofilm extracellular matrix. Dentin microtensile strengths were
      also measured. Cured adhesives containing DMADDM could greatly reduce metabolic
      activity and lactic acid production during the development of S. mutans biofilms
      (p < 0.05). In earlier stages of biofilm development, there were no significant
      differences of inhibitory effects between the 2.5% DMADDM and 5% DMADDM group.
      However, after 72 h, the anti-biofilm effects of adhesives containing 5% DMADDM
      were significantly stronger than any other group. Incorporation of DMADDM into
      adhesive did not adversely affect dentin bond strength. In conclusion, adhesives
      containing DMADDM inhibited the growth, lactic acid production and EPS metabolism
      of S. mutans biofilm at different stages, with no adverse effect on its dentin
      adhesive bond strength. The bonding agents have the potential to control dental
      biofilms and combat tooth decay, and DMADDM is promising for use in a wide range
      of dental adhesive systems and restoratives. 

PMID- 25046751
TI  - Strengthening the Reporting of Observational Studies in Epidemiology (STROBE):
      explanation and elaboration.
AB  - Much medical research is observational. The reporting of observational studies is
      often of insufficient quality. Poor reporting hampers the assessment of the
      strengths and weaknesses of a study and the generalisability of its results.
      Taking into account empirical evidence and theoretical considerations, a group of
      methodologists, researchers, and editors developed the Strengthening the
      Reporting of Observational Studies in Epidemiology (STROBE) recommendations to
      improve the quality of reporting of observational studies. The STROBE Statement
      consists of a checklist of 22 items, which relate to the title, abstract,
      introduction, methods, results and discussion sections of articles. Eighteen
      items are common to cohort studies, case-control studies and cross-sectional
      studies and four are specific to each of the three study designs. The STROBE
      Statement provides guidance to authors about how to improve the reporting of
      observational studies and facilitates critical appraisal and interpretation of
      studies by reviewers, journal editors and readers. This explanatory and
      elaboration document is intended to enhance the use, understanding, and
      dissemination of the STROBE Statement. The meaning and rationale for each
      checklist item are presented. For each item, one or several published examples
      and, where possible, references to relevant empirical studies and methodological
      literature are provided. Examples of useful flow diagrams are also included. The
      STROBE Statement, this document, and the associated Web site (http://www.strobe
      statement.org/) should be helpful resources to improve reporting of observational
      research. 

PMID- 25046752
TI  - Expression of a functional jasmonic acid carboxyl methyltransferase is negatively
      correlated with strawberry fruit development.
AB  - The volatile metabolite methyl jasmonate (MeJA) plays an important role in intra-
      and interplant communication and is involved in diverse biological processes. In
      this study, we report the cloning and functional characterization of a S-adenosyl
      l-methionine:jasmonic acid carboxyl methyltransferase (JMT) from Fragaria vesca
      and Fragaria*ananassa. Biochemical assays and comprehensive transcript analyses
      showed that JMT has been erroneously annotated as gene fusion with a carboxyl
      methyltransferase (CMT) (gene15184) in the first published genome sequence of F.
      vesca. Recombinant FvJMT catalyzed the formation of MeJA with KM value of 22.3MUM
      while FvCMT and the fusion protein were almost inactive. Activity of JMT with
      benzoic acid and salicylic acid as substrates was less than 1.5% of that with JA.
      Leucine at position 245, an amino acid missing in other JMT sequences is
      essential for activity of FvJMT. In accordance with MeJA levels, JMT transcript
      levels decreased steadily during strawberry fruit ripening, as did the expression
      levels of JA biosynthesis and regulatory genes. It appears that CMT has
      originated by a recent duplication of JMT and lost its enzymatic activity toward
      JA. In the newest version of the strawberry genome sequence (June 2014) CMT and
      JMT are annotated as separate genes in accordance with differential temporal and
      spatial expression patterns of both genes in Fragaria sp. In conclusion, MeJA,
      the inactive derivative of JA, is probably involved in early steps of fruit
      development by modulating the levels of the active plant hormone JA. 

PMID- 25046753
TI  - Higher peroxidase activity, leaf nutrient contents and carbon isotope composition
      changes in Arabidopsis thaliana are related to rutin stress.
AB  - Rutin, a plant secondary metabolite that is used in cosmetics and food additive
      and has known medicinal properties, protects plants from UV-B radiation and
      diseases. Rutin has been suggested to have potential in weed management, but its
      mode of action at physiological level is unknown. Here, we report the
      biochemical, physiological and oxidative response of Arabidopsis thaliana to
      rutin at micromolar concentrations. It was found that fresh weight; leaf mineral
      contents (nitrogen, sodium, potassium, copper and aluminum) were decreased
      following 1 week exposure to rutin. Arabidopsis roots generate significant
      amounts of reactive oxygen species after rutin treatment, consequently increasing
      membrane lipid peroxidation, decreasing leaf Ca(2+), Mg(2+), Zn(2+), Fe(2+)
      contents and losing root viability. Carbon isotope composition in A. thaliana
      leaves was less negative after rutin application than the control. Carbon isotope
      discrimination values were decreased following rutin treatment, with the highest
      reduction compared to the control at 750MUM rutin. Rutin also inhibited the ratio
      of CO2 from leaf to air (ci/ca) at all concentrations. Total protein contents in
      A. thaliana leaves were decreased following rutin treatment. It was concluded
      carbon isotope discrimination coincided with protein degradation, increase lipid
      peroxidation and a decrease in ci/ca values may be the primary action site of
      rutin. The present results suggest that rutin possesses allelopathic potential
      and could be used as a candidate to develop environment friendly natural
      herbicide. 

PMID- 25046754
TI  - Abscisic acid-induced rearrangement of intracellular structures associated with
      freezing and desiccation stress tolerance in the liverwort Marchantia polymorpha.
AB  - The plant growth regulator abscisic acid (ABA) is known to be involved in
      triggering responses to various environmental stresses such as freezing and
      desiccation in angiosperms, but little is known about its role in basal land
      plants, especially in liverworts, representing the earliest land plant lineage.
      We show here that survival rate after freezing and desiccation of Marchantia
      polymorpha gemmalings was increased by pretreatment with ABA in the presence of
      increasing concentrations of sucrose. ABA treatment increased accumulation of
      soluble sugars in gemmalings, and sugar accumulation was further increased by
      addition of sucrose to the culture medium. ABA treatment of gemmalings also
      induced accumulation of transcripts for proteins with similarity to late
      embryogenesis abundant (LEA) proteins, which accumulate in association with
      acquisition of desiccation tolerance in maturing seeds. Observation by light and
      electron microscopy indicated that the ABA treatment caused fragmentation of
      vacuoles with increased cytosolic volume, which was more prominent in the
      presence of a high concentration of external sucrose. ABA treatment also
      increased the density of chloroplast distribution and remarkably enlarged their
      volume. These results demonstrate that ABA induces drastic physiological changes
      in liverwort cells for stress tolerance, accompanied by accumulation of
      protectants against dehydration and rearrangement and morphological alterations
      of cellular organelles. 

PMID- 25046755
TI  - Adaptive changes in photosynthetic performance and secondary metabolites during
      white dead nettle micropropagation.
AB  - The white dead nettle, Lamium album L., is an herb that has been successfully
      cultivated under in vitro conditions. The L. album micropropagation system offers
      a combination of factors (light intensity, temperature, carbon dioxide (CO2)
      level, humidity) that are limiting for plant growth and bioactive capacity. To
      get a better understanding of the mechanism of plant acclimation towards
      environmental changes, we performed a comparative investigation on primary and
      secondary metabolism in fully expanded L. album leaves during the consecutive
      growth in in situ, in vitro, and ex vitro conditions. Although the genetic
      identity was not affected, structural and physiological deviations were observed,
      and the level of bioactive compounds was modified. During in vitro cultivation,
      the L. album leaves became thinner with unaffected overall leaf organization, but
      with a reduced number of palisade mesophyll layers. Structural deviation of the
      thylakoid membrane system was detected. In addition, the photosystem 2 (PS2)
      electron transport was retarded, and the plants were more vulnerable to light
      damage as indicated by the decreased photoprotection ability estimated by
      fluorescence parameters. The related CO2 assimilation and transpiration rates
      were subsequently reduced, as were the content of essential oils and phenolics.
      Transfer of the plants ex vitro did not increase the number of palisade numbers,
      but the chloroplast structure and PS2 functionality were recovered. Strikingly,
      the rates of CO2 assimilation and transpiration were increased compared to in
      situ control plants. While the phenolics content reached normal levels during ex
      vitro growth, the essential oils remained low. Overall, our study broadens the
      understanding about the nature of plant responses towards environmental
      conditions. 

PMID- 25046756
TI  - Effect of 1-naphthaleneacetic acid on organic acid exudation by the roots of
      white lupin plants grown under phosphorus-deficient conditions.
AB  - The effect of NAA (1-naphthaleneacetic acid) on organic acid exudation in white
      lupin plants grown under phosphorus deficiency was investigated. Plants were
      sampled periodically for collecting of organic acids (citrate, malate,
      succinate), and also were used to study the effect on proton extrusion and
      release of Na(+), K(+), Ca(2+) and Mg(2+). The tissues were later processed to
      quantify the organic acids in tissues, the phosphorus content and the effects on
      plant biomass. The exogenous addition of NAA led to an increase in organic acid
      exudation, but this response was not proportional to the concentration of the
      dose applied, noticing the largest increments with NAA 10(-8)M. In contrast the
      increase in root weight was proportional to the dose applied, which shows that
      with higher doses the roots produced are not of proteoid type. Proton extrusion
      and the release of cations were related to the NAA dose, the first was
      proportional to the dose applied and the second inversely proportional. Regarding
      the analysis of tissues, the results of citrate and phosphorus content in shoots
      show that the overall status of these parts are the main responsible of the
      organic acids exuded. NAA served as an enhancer of the organic acid exudation
      that occurs under phosphorus deficient conditions, with a response that depends
      on the dose applied, not only in its magnitude, but also in the mechanism of
      action of the plant hormone. 

PMID- 25046757
TI  - Salt-induced delay in cotyledonary globulin mobilization is abolished by
      induction of proteases and leaf growth sink strength at late seedling
      establishment in cashew.
AB  - Seedling establishment in saline conditions is crucial for plant survival and
      productivity. This study was performed to elucidate the biochemical and
      physiological mechanisms involved with the recovery and establishment of cashew
      seedlings subjected to salinity. The changes in the Na+ levels and K/Na ratios,
      associated with relative water content, indicated that osmotic effects were more
      important than salt toxicity in the inhibition of seedling growth and
      cotyledonary protein mobilization. Salinity (50mM NaCl) induced a strong delay in
      protein breakdown and amino acid accumulation in cotyledons, and this effect was
      closely related to azocaseinolytic and protease activities. In parallel, proline
      and free amino acids accumulated in the leaves whereas the protein content
      decreased. Assays with specific inhibitors indicated that the most important
      proteases in cotyledons were of serine, cysteine and aspartic types. Proteomic
      analysis revealed that most of the cashew reserve proteins are 11S globulin-type
      and that these proteins were similarly degraded under salinity. In the late
      establishment phase, the salt-treated seedlings displayed an unexpected recovery
      in terms of leaf growth and N mobilization from cotyledon to leaves. This
      recovery coordinately involved a great leaf expansion, decreased amino acid
      content and increased protein synthesis in leaves. This response occurred in
      parallel with a prominent induction in the cotyledon proteolytic activity.
      Altogether, these data suggest that a source-sink mechanism involving leaf growth
      and protein synthesis may have acted as an important sink for reserve
      mobilization contributing to the seedling establishment under salinity. The amino
      acids that accumulated in the leaves may have exerted negative feedback to act as
      a signal for the induction of protease activity in the cotyledon. Overall, these
      mechanisms employed by cashew seedlings may be part of an adaptive process for
      the efficient rescue of cotyledonary proteins, as the cashew species originates
      from an environment with N-poor soil and high salinity. 

PMID- 25046758
TI  - RNAi-mediated pinoresinol lariciresinol reductase gene silencing in flax (Linum
      usitatissimum L.) seed coat: consequences on lignans and neolignans accumulation.
AB  - RNAi technology was applied to down regulate LuPLR1 gene expression in flax
      (Linum usitatissimum L.) seeds. This gene encodes a pinoresinol lariciresinol
      reductase responsible for the synthesis of (+)-secoisolariciresinol diglucoside
      (SDG), the major lignan accumulated in the seed coat. If flax lignans biological
      properties and health benefits are well documented their roles in planta remain
      unclear. This loss of function strategy was developed to better understand the
      implication of the PLR1 enzyme in the lignan biosynthetic pathway and to provide
      new insights on the functions of these compounds. RNAi plants generated exhibited
      LuPLR1 gene silencing as demonstrated by quantitative RT-PCR experiments and the
      failed to accumulate SDG. The accumulation of pinoresinol the substrate of the
      PLR1 enzyme under its diglucosylated form (PDG) was increased in transgenic seeds
      but did not compensate the overall loss of SDG. The monolignol flux was also
      deviated through the synthesis of 8-5' linked neolignans dehydrodiconiferyl
      alcohol glucoside (DCG) and dihydro-dehydrodiconiferyl alcohol glucoside (DDCG)
      which were observed for the first time in flax seeds. 

PMID- 25046759
TI  - Trichoderma spp. alleviate phytotoxicity in lettuce plants (Lactuca sativa L.)
      irrigated with arsenic-contaminated water.
AB  - The influence of two strains of Trichoderma (T. harzianum strain T22 and T.
      atroviride strain P1) on the growth of lettuce plants (Lactuca sativa L.)
      irrigated with As-contaminated water, and their effect on the uptake and
      accumulation of the contaminant in the plant roots and leaves, were studied.
      Accumulation of this non-essential element occurred mainly into the root system
      and reduced both biomass development and net photosynthesis rate (while altering
      the plant P status). Plant growth-promoting fungi (PGPF) of both Trichoderma
      species alleviated, at least in part, the phytotoxicity of As, essentially by
      decreasing its accumulation in the tissues and enhancing plant growth, P status
      and net photosynthesis rate. Our results indicate that inoculation of lettuce
      with selected Trichoderma strains may be helpful, beside the classical biocontrol
      application, in alleviating abiotic stresses such as that caused by irrigation
      with As-contaminated water, and in reducing the concentration of this metalloid
      in the edible part of the plant. 

PMID- 25046760
TI  - Drought-inhibited ribulose-1,5-bisphosphate carboxylase activity is mediated
      through increased release of ethylene and changes in the ratio of polyamines in
      pakchoi.
AB  - To study the mechanisms of drought inhibiting photosynthesis and the role of PAs
      and ethylene, the photosynthetic rate (Pn), the maximal photochemical efficiency
      of PSII (Fv/Fm), the intercellular CO2 concentration (Ci), photorespiratory rate
      (Pr), the amount of chlorophyll (chl), antioxidant enzyme activity, ethylene
      levels, RuBPC (ribulose-1,5-bisphosphate carboxylase) activity and endogenous
      polyamine levels of pakchoi were examined, and an inhibitor of S
      adenosylmethionine decarboxylase (SAMDC) and an inhibitor of ethylene synthesis
      and spermidine (Spd) were used to induce the change of endogenous polyamine
      levels. The results show that drought induced a decrease in Pn and RuBPC
      activity, an increase in the intercellular CO2 concentration (Ci), but no change
      in the actual photochemical efficiency of PSII (PhiPSII), and chlorophyll
      content. In addition, drought caused an increase in the free putrescine (fPut),
      the ethylene levels, a decrease in the Spd and spermine (Spm) levels, and the
      PAs/fPut ratio in the leaves. The exogenous application of Spd and amino
      oxiacetic acid (AOAA, an inhibitor of ethylene synthesis) markedly reversed these
      drought-induced effects on polyamine, ethylene, Pn, the PAs/fPut ratio and
      RuBPCase activity in leaves. Methylglyoxal-bis(guanylhydrazone) (MGBG), an
      inhibitor of SAMDC resulting in the inability of activated cells to synthesize
      Spd and Spm, exacerbates the negative effects induced by drought. These results
      suggest that the decrease in Pn is at least partially attributed to the decrease
      of RuBPC activity under drought stress and that drought inhibits RuBPC activity
      by decreasing the ratio of PAs/fPut and increasing the release of ethylene. 

PMID- 25046761
TI  - The Camelina aquaporin CsPIP2;1 is regulated by phosphorylation at Ser273, but
      not at Ser277, of the C-terminus and is involved in salt- and drought-stress
      responses.
AB  - Aquaporin (AQP) proteins are involved in water homeostasis in cells at all
      taxonomic levels of life. Phosphorylation of some AQPs has been proposed to
      regulate water permeability via gating of the channel itself. We analyzed plasma
      membrane intrinsic proteins (PIP) from Camelina and characterized their
      biological functions under both stressful and favorable conditions. A three
      dimensional theoretical model of the Camelina AQP proteins was built by homology
      modeling which could prove useful in further functional characterization of AQPs.
      CsPIP2;1 was strongly and constitutively expressed in roots and leaves of
      Camelina, suggesting that this gene is related to maintenance of homeostasis
      during salt and drought stresses. CsPIP2s exhibited water channel activity in
      Xenopus oocytes. We then examined the roles of CsPIP2;1 phosphorylation at Ser273
      and Ser277 in the regulation of water permeability using phosphorylation mutants.
      A single deletion strain of CsPIP2;1 was generated to serve as the primary host
      for testing AQP expression constructs. A Ser277 to alanine mutation (to prevent
      phosphorylation) did not change CsPIP2;1 water permeability while a Ser273
      mutation to alanine did affect water permeability. Furthermore, a CsPIP2;1 point
      mutation when ectopically expressed in yeast resulted in lower growth in salt and
      drought conditions compared with controls, and confirmation of Ser273 as the
      phosphorylation site. Our results support the idea that post-translational
      modifications in the Ser273 regulatory domains of the C-terminus fine tune water
      flux through CsPIP2;1. 

PMID- 25046762
TI  - Approach to engineer tomato by expression of AtHMA4 to enhance Zn in the aerial
      parts.
AB  - The aim of this work was to assess the potential for using AtHMA4 to engineer
      enhanced efficiency of Zn translocation to shoots, and to increase the Zn
      concentration in aerial tissues of tomato. AtHMA4, a P1B-ATPase, encodes a Zn
      export protein known to be involved in the control of Zn root-to-shoot
      translocation. In this work, 35S::AtHMA4 was expressed in tomato (Lycopersicon
      esculentum var. Beta). Wild-type and transgenic plants were tested for Zn and Cd
      tolerance; Zn, Fe and Cd accumulation patterns, and for the expression of
      endogenous Zn/Fe-homeostasis genes. At 10MUM Zn exposure, a higher Zn
      concentration was observed in leaves of AtHMA4-expressing lines compared to wild
      type, which is promising in terms of Zn biofortification. AtHMA4 also transports
      Cd and at 0.25MUM Cd the transgenic plants showed similar levels of this element
      in leaves to wild-type but lower levels in roots, therefore indicating a
      reduction of Cd uptake due to AtHMA4 expression. Expression of this transgene
      AtHMA4 also resulted in distinct changes in Fe accumulation in Zn-exposed plants,
      and Fe/Zn-accumulation in Cd-exposed plants, even though Fe is not a substrate
      for AtHMA4. Analysis of the transcript abundance of key Zn/Fe-homeostasis genes
      showed that the pattern was distinct for transgenic and wild-type plants. The
      reduction of Fe accumulation observed in AtHMA4-transformants was accompanied by
      up-regulation of Fe-deficiency marker genes (LeFER, LeFRO1, LeIRT1), whereas down
      regulation was detected in plants with the status of Fe-sufficiency. Furthermore,
      results strongly suggest the importance of the up-regulation of LeCHLN in the
      roots of AtHMA4-expressing plants for efficient translocation of Zn to the
      shoots. Thus, the modifications of Zn/Fe/Cd translocation to aerial plant parts
      due to AtHMA4 expression are closely related to the alteration of the endogenous
      Zn-Fe-Cd cross-homeostasis network of tomato. 

PMID- 25046764
TI  - Monolayer MoS2 heterojunction solar cells.
AB  - We realized photovoltaic operation in large-scale MoS2 monolayers by the
      formation of a type-II heterojunction with p-Si. The MoS2 monolayer introduces a
      built-in electric field near the interface between MoS2 and p-Si to help
      photogenerated carrier separation. Such a heterojunction photovoltaic device
      achieves a power conversion efficiency of 5.23%, which is the highest efficiency
      among all monolayer transition-metal dichalcogenide-based solar cells. The
      demonstrated results of monolayer MoS2/Si-based solar cells hold the promise for
      integration of 2D materials with commercially available Si-based electronics in
      highly efficient devices.

PMID- 25046763
TI  - Comparative proteomic analysis of amaranth mesophyll and bundle sheath
      chloroplasts and their adaptation to salt stress.
AB  - The effect of salt stress was analyzed in chloroplasts of Amaranthus cruentus
      var. Amaranteca, a plant NAD-malic enzyme (NAD-ME) type. Morphology of
      chloroplasts from bundle sheath (BSC) and mesophyll (MC) was observed by
      transmission electron microscopy (TEM). BSC and MC from control plants showed
      similar morphology, however under stress, changes in BSC were observed. The
      presence of ribulose bisphosphate carboxylase/oxygenase (RuBisCO) was confirmed
      by immunohistochemical staining in both types of chloroplasts. Proteomic profiles
      of thylakoid protein complexes from BSC and MC, and their changes induced by salt
      stress were analyzed by blue-native polyacrylamide gel electrophoresis followed
      by SDS-PAGE (2-D BN/SDS-PAGE). Differentially accumulated protein spots were
      analyzed by LC-MS/MS. Although A. cruentus photosynthetic tissue showed the Kranz
      anatomy, the thylakoid proteins showed some differences at photosystem structure
      level. Our results suggest that A. cruentus var. Amaranteca could be better
      classified as a C3-C4 photosynthetic plant. 

PMID- 25046765
TI  - Reranking docking poses using molecular simulations and approximate free energy
      methods.
AB  - Fast and accurate identification of active compounds is essential for effective
      use of virtual screening workflows. Here, we have compared the ligand-ranking
      efficiency of the linear interaction energy (LIE) method against standard docking
      approaches. Using a trypsin set of 1549 compounds, we performed 12,250 molecular
      dynamics simulations. The LIE method proved effective but did not yield results
      significantly better than those obtained with docking codes. The entire database
      of simulations is released. 

PMID- 25046766
TI  - Metal-independent reduction of hydrogen peroxide by semiquinones.
AB  - The quinones 1,4-naphthoquinone (NQ), tetramethyl-1,4-benzoquinone (DQ), 2-methyl
      1,4-naphthoquinone (MNQ), 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UBQ-0), 2,6
      dimethylbenzoquinone (DMBQ), 2,6-dimethoxybenzoquinone (DMOBQ), and 9,10
      phenanthraquinone (PHQ) enhance the rate of H2O2 reduction by ascorbate, under
      anaerobic conditions, as detected from the amount of methane produced after
      hydroxyl radical reaction with dimethyl sulfoxide. The amount of methane produced
      increases with an increase in the quinone one-electron reduction potential. The
      most active quinone in this series, PHQ, is only 14% less active than the classic
      Fenton reagent cation, Fe(2+), at the same concentration. Since PHQ is a common
      toxin present in diesel combustion smoke, the possibility that PHQ-mediated
      catalysis of hydroxyl radical formation is similar to that of Fe(2+) adds another
      important pathway to the modes in which PHQ can execute its toxicity. Because
      quinones are known to enhance the antitumor activity of ascorbate and because
      ascorbate enhances the formation of H2O2 in tissues, the quinone-mediated
      reduction of H2O2 should be relevant to this type of antitumor activity,
      especially under hypoxic conditions. 

PMID- 25046767
TI  - A one-pot, three-component reaction for the synthesis of novel 7
      arylbenzo[c]acridine-5,6-diones.
AB  - A one pot domino protocol for an efficient synthesis of 7-arylbenzo[c]acridine
      5,6-diones, with a novel nucleus, has been developed by reacting 2
      hydroxynaphthalene-1,4-dione, aromatic aldehydes and aromatic amines using
      environmentally benevolent p-toluene sulphonic acid as a catalyst. An exciting
      feature of this communication is the reaction mechanism that depends on the
      reaction solvent. 

PMID- 25046768
TI  - Systematic analysis of Persson's contact mechanics theory of randomly rough
      elastic surfaces.
AB  - We systematically check explicit and implicit assumptions of Persson's contact
      mechanics theory. It casts the evolution of the pressure distribution Pr(p) with
      increasing resolution of surface roughness as a diffusive process, in which
      resolution plays the role of time. The tested key assumptions of the theory are:
      (a) the diffusion coefficient is independent of pressure p, (b) the diffusion
      process is drift-free at any value of p, (c) the point p = 0 acts as an absorbing
      barrier, i.e., once a point falls out of contact, it never re-enters again, (d)
      the Fourier component of the elastic energy is only populated if the appropriate
      wave vector is resolved, and (e) it no longer changes when even smaller
      wavelengths are resolved. Using high-resolution numerical simulations, we
      quantify deviations from these approximations and find quite significant
      discrepancies in some cases. For example, the drift becomes substantial for small
      values of p, which typically represent points in real space close to a contact
      line. On the other hand, there is a significant flux of points re-entering
      contact. These and other identified deviations cancel each other to a large
      degree, resulting in an overall excellent description for contact area, contact
      geometry, and gap distribution functions. Similar fortuitous error cancellations
      cannot be guaranteed under different circumstances, for instance when
      investigating rubber friction. The results of the simulations may provide
      guidelines for a systematic improvement of the theory.

PMID- 25046769
TI  - Sensitivity encoding for fast (1) H MR spectroscopic imaging water reference
      acquisition.
AB  - PURPOSE: Accurate and fast (1) H MR spectroscopic imaging (MRSI) water reference
      scans are important for absolute quantification of metabolites. However, the
      additional acquisition time required often precludes the water reference
      quantitation method for MRSI studies. Sensitivity encoding (SENSE) is a
      successful MR technique developed to reduce scan time. This study quantitatively
      assesses the accuracy of SENSE for water reference MRSI data acquisition,
      compared with the more commonly used reduced resolution technique. METHODS: 2D
      MRSI water reference data were collected from a phantom and three volunteers at 3
      Tesla for full acquisition (306 s); 2* reduced resolution (64 s) and SENSE R = 3
      (56 s) scans. Water amplitudes were extracted using MRS quantitation software
      (TARQUIN). Intensity maps and Bland-Altman statistics were generated to assess
      the accuracy of the fast-MRSI techniques. RESULTS: The average mean and standard
      deviation of differences from the full acquisition were 2.1 +/- 3.2% for SENSE
      and 10.3 +/- 10.7% for the reduced resolution technique, demonstrating that SENSE
      acquisition is approximately three times more accurate than the reduced
      resolution technique. CONCLUSION: SENSE was shown to accurately reconstruct water
      reference data for the purposes of in vivo absolute metabolite quantification,
      offering significant improvement over the more commonly used reduced resolution
      technique.

PMID- 25046771
TI  - The measurement and importance of non-motor symptoms in Parkinson disease.

PMID- 25046770
TI  - Developmental regulation of glial cell phagocytic function during Drosophila
      embryogenesis.
AB  - The proper removal of superfluous neurons through apoptosis and subsequent
      phagocytosis is essential for normal development of the central nervous system
      (CNS). During Drosophila embryogenesis, a large number of apoptotic neurons are
      efficiently engulfed and degraded by phagocytic glia. Here we demonstrate that
      glial proficiency to phagocytose relies on expression of phagocytic receptors for
      apoptotic cells, SIMU and DRPR. Moreover, we reveal that the phagocytic ability
      of embryonic glia is established as part of a developmental program responsible
      for glial cell fate determination and is not triggered by apoptosis per se.
      Explicitly, we provide evidence for a critical role of the major regulators of
      glial identity, gcm and repo, in controlling glial phagocytic function through
      regulation of SIMU and DRPR specific expression. Taken together, our study
      uncovers molecular mechanisms essential for establishment of embryonic glia as
      primary phagocytes during CNS development. 

PMID- 25046772
TI  - Supramolecular interaction between a hydrophilic coumarin dye and macrocyclic
      hosts: spectroscopic and calorimetric study.
AB  - The photophysics of a hydrophilic molecule, 7-(diethylamino)-coumarin-3
      carboxylic acid (7-DCCA), was studied in the presence of two macrocycles, (2
      hydroxypropyl)-gamma-cyclodextrin and cucurbit[7]uril. We have used steady-state
      absorption, fluorescence, and time-resolved fluorescence emission spectroscopy;
      Fourier transform infrared (FTIR) spectroscopy; (1)H NMR spectroscopy; and
      isothermal titration calorimetry (ITC) to confirm the supramolecular host-guest
      complex formation. The spectral properties of 7-DCCA were modulated in the
      presence of both macrocycles. It was assigned that 7-DCCA forms a 1:2 complex
      with (2-hydroxypropyl)-gamma-cyclodextrin and cucurbit[7]uril. The large
      modulation of the emission properties of 7-DCCA in the presence of the
      macrocycles indicates the formation of supramolecular complexes. A significant
      shift in the bond vibration frequencies in the FTIR studies showed encapsulation
      of the dyes in the hydrophobic cavity of the macrocycles. This is further
      substantiated by the (1)H NMR studies, in which the upfield and downfield shifts
      of the protons were observed in both the aliphatic and aromatic region in the
      presence of macrocycles. The time-resolved anisotropy measurements further
      reinforce the conception of host-guest supramolecular complex formation because,
      in both cases, the rotational relaxation time increases significantly compared to
      that in water. A deeper understanding between the differences in interaction of
      an anionic molecule with cucurbit[7]uril and (2-hydroxypropyl)-gamma-cyclodextrin
      will be achieved through this work. From the ITC measurement, we have formulated
      the forces due to complex formation. 

PMID- 25046773
TI  - Combined DNA methylation and gene expression profiling in gastrointestinal
      stromal tumors reveals hypomethylation of SPP1 as an independent prognostic
      factor.
AB  - Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns
      according to localization, genotype and aggressiveness. DNA methylation at CpG
      dinucleotides is an important mechanism for regulation of gene expression. We
      performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer
      related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression
      analysis in 22 GISTs, to identify signatures associated with clinicopathological
      parameters and prognosis. Principal component analysis revealed distinct DNA
      methylation patterns associated with anatomical localization, genotype, mitotic
      counts and clinical follow-up. Methylation of a single CpG dinucleotide in the
      non-CpG island promoter of SPP1 was significantly correlated with shorter disease
      free survival. Hypomethylation of this CpG was an independent prognostic
      parameter in a multivariate analysis compared to anatomical localization,
      genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical
      follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the
      functional impact of SPP1 protein on tumorigenesis-related signaling pathways was
      demonstrated. In summary, SPP1 promoter methylation is a novel and independent
      prognostic parameter in GISTs, and might be helpful in estimating the
      aggressiveness of GISTs from the intermediate-risk category. 

PMID- 25046775
TI  - Diagnostic efficacy of diffusion-weighted MRI for pre-operative assessment of
      myometrial and cervical invasion and pelvic lymph node metastasis in endometrial
      carcinoma.
AB  - INTRODUCTION: To determine the diagnostic accuracy of diffusion-weighted magnetic
      resonance imaging (DW-MRI) for the pre-operative assessment of patients with
      endometrial carcinoma and to assess myometrial and cervical invasion as well as
      pelvic lymph node metastasis. METHODS: Fifty-eight women who underwent surgery
      for histopathologically confirmed endometrial carcinoma were included in the
      current study. Prior to surgery, patients were evaluated using pelvic DW-MRI and
      gadolinium-enhanced T1-weighted imaging (Gd-T1WI). Gd-T1WI was evaluated together
      with T2-weighted images. DW-MR images were obtained in the axial plane using echo
      planar spin-echo pulse sequences with different b factors. Endometrial carcinomas
      were observed as areas of increased intensity on DW-MRI images, and their
      intensity was compared with the surrounding hypo-intense myometrium. Pre
      operative DW-MRI and Gd-T1WI results were compared with post-operative
      histopathological findings that served as reference standards. RESULTS: The
      sensitivity, specificity, positive (PPV) and negative predictive values (NPV),
      and diagnostic accuracy of DW-MRI for differentiation between superficial
      myometrial invasion and deep myometrial invasion were 85%, 89%, 81%, 92% and 88%,
      respectively. The sensitivity, specificity and diagnostic accuracy rates were
      82%, 91% and 89.6% for cervical invasion and 100%, 96% and 96.5% for pelvic lymph
      node metastasis, respectively. The sensitivity, specificity, PPV and NPV, and
      diagnostic accuracy of Gd-T1WI for differentiation between superficial myometrial
      invasion and deep myometrial invasion were 85%, 81.5%, 71%, 91% and 83%,
      respectively. The sensitivity, specificity and diagnostic accuracy were 73%, 89%
      and 86% for cervical invasion, respectively. CONCLUSIONS: These findings suggest
      that DW-MRI may be a good diagnostic tool with high sensitivity and specificity
      for assessing myometrial invasion and detecting tumour extension. We suggest that
      DW-MRI should be considered as a routine part of the pre-operative pelvic MRI in
      all patients with endometrial carcinoma.

PMID- 25046776
TI  - Double duty: does epidural labor analgesia reduce both pain and postpartum
      depression?

PMID- 25046777
TI  - The value of sedation by anesthesia teams for complex endoscopy: perhaps not what
      you'd think.

PMID- 25046778
TI  - The efficacy and safety of liquid stored blood and storage duration: a confused
      subject; are patients confused?

PMID- 25046779
TI  - A twitch in time.

PMID- 25046780
TI  - Nicotine is out: nicotinic agonists may have utility as analgesics.

PMID- 25046781
TI  - Intraoperative analgesic titration: the hunting of the snark.

PMID- 25046782
TI  - Making sense of surgical risk when the data aren't perfect.

PMID- 25046783
TI  - Complex left atrial wall dissection after combined aortic and mitral valve
      replacement.

PMID- 25046784
TI  - An essay on 35 years of the Society of Cardiovascular Anesthesiologists.
AB  - This is an historical account of the accomplishments of the Society of
      Cardiovascular Anesthesiologists from its founding in 1989 to the present. It is
      written on the occasion of the 35th anniversary of the founding of this
      organization. The society accomplishments include providing a means to educate
      anesthesiologists and others about the perioperative care of patients undergoing
      cardiac, thoracic, and vascular surgery. The society has led accreditation of
      transesophageal echocardiography and education in cardiothoracic anesthesia. The
      society publishes a section within Anesthesia & Analgesia and supports
      investigation by providing a forum for the discussion of research and funding
      peer-reviewed projects. The first 35 years of the Society of Cardiovascular
      Anesthesiologists has been remarkable in all that has been accomplished. 

PMID- 25046785
TI  - Office-based anesthesia: safety and outcomes.
AB  - The increasing volume of office-based medical and surgical procedures has
      fostered the emergence of office-based anesthesia (OBA), a subspecialty within
      ambulatory anesthesia. The growth of OBA has been facilitated by numerous trends,
      including innovations in medical and surgical procedures and anesthetic drugs, as
      well as improved provider reimbursement and greater convenience for patients.
      There is a lack of randomized controlled trials to determine how office-based
      procedures and anesthesia affect patient morbidity and mortality. As a result,
      studies on this topic are retrospective in nature. Some of the early literature
      broaches concerns about the safety of office-based procedures and anesthesia.
      However, more recent data have shown that care in ambulatory settings is
      comparable to hospitals and ambulatory surgery centers, especially when offices
      are accredited and their proceduralists are board-certified. Office-based suites
      can continue to enhance the quality of care that they deliver to patients by
      engaging in proper procedure and patient selection, provider credentialing,
      facility accreditation, and incorporating patient safety checklists and
      professional society guidelines into practice. These strategies aiming at patient
      morbidity and mortality in the office setting will be increasingly important as
      more states, and possibly the federal government, exercise regulatory authority
      over the ambulatory setting. We explore these trends, their implications for
      patient safety, strategies for minimizing patient complications and mortality in
      OBA, and future developments that could impact the field. 

PMID- 25046786
TI  - Coagulation, flocculation, and denaturation: a century of research into
      protoplasmic theories of anesthesia.
AB  - Within two decades of the discovery of anesthesia, the physicochemical concept of
      colloid and the biological concept of protoplasm had emerged. Fusion of these
      concepts into a theoretical framework, which has been largely forgotten decades
      ago, promised to uncover fundamental biological truths and determined research
      into anesthetic mechanisms for a century after "Ether Day." Observations of
      optical changes in unstained tissue were condensed into a theory of anesthesia by
      coagulation of protoplasm in the 1870s. The underlying hypotheses, conformational
      changes of proteins within the protoplasm cause all behavioral effects of
      anesthesia, continued to be pursued well into the 20th century. The goal was to
      explain anesthesia using physical chemistry within a fundamental cell biological
      framework. This large body of work, swept aside during the decades of lipid
      membrane hegemony, has remained in obscurity even after proteins in excitable
      membranes became firmly established as mediators of the immediate anesthetic
      effects. This article is a reminder of the prolonged interdisciplinary research
      effort dedicated to "protoplasmic theories" at a time when attention is
      increasingly directed toward examining the nature of (un)consciousness well as
      noncanonical consequences of anesthetic exposure that are not easily accounted
      for within conventional pharmacological concepts. 

PMID- 25046787
TI  - Supplemental postoperative oxygen does not reduce surgical site infection and
      major healing-related complications from bariatric surgery in morbidly obese
      patients: a randomized, blinded trial.
AB  - BACKGROUND: Morbidly obese patients are at high risk for perioperative
      complications, including surgical site infections. Baseline arterial oxygenation
      is low in the morbidly obese, leading to low tissue oxygenation, which in turn is
      a primary determinant of infection risk. We therefore tested the hypothesis that
      extending intraoperative supplemental oxygen 12 to 16 hours into the
      postoperative period reduces the risk of surgical site infection and healing
      related complications. METHODS: Morbidly obese patients having open or
      laparoscopic bariatric surgery were given 80% inspired oxygen intraoperatively.
      Postoperatively, patients were randomly assigned to either 2 L/min of oxygen via
      nasal cannula or approximately 80% supplemental inspired oxygen after tracheal
      extubation until the first postoperative morning. The risks of surgical site
      infection and of major healing-related complications were evaluated 60 days after
      surgery. RESULTS: In a preplanned interim analysis based on the initial 400
      patients, the overall observed incidence of the collapsed composite of major
      complications was 13.3%; the observed incidence of components of the composite
      outcome ranged from 0% (peritonitis) to 8.5% (surgical wound infection). The
      estimated relative risk of any >=1 major complications occurring within the first
      60 days after surgery, adjusting for study site, was 0.94 (95% confidence
      interval, 0.52-1.68) (P = 0.80, Cochran-Mantel-Haenszel). The Executive Committee
      thus stopped the trial for futility. CONCLUSIONS: Supplemental postoperative
      oxygen does not reduce the risk of surgical site infection rate and healing
      related postoperative complications in patients having gastric bypass surgery.

PMID- 25046788
TI  - Pierre Robin Sequence: a perioperative review.
AB  - The clinical triad of micrognathia (small mandible), glossoptosis (backward,
      downward displacement of the tongue), and airway obstruction defines the Pierre
      Robin sequence (PRS). Airway obstruction and respiratory distress are clinical
      hallmarks. Patients may present with stridor, retractions, and cyanosis. Severe
      obstruction results in feeding difficulty, reflux, and failure to thrive.
      Treatment options depend on the severity of airway obstruction and include prone
      positioning, nasopharyngeal airways, tongue lip adhesion, mandibular distraction
      osteogenesis, and tracheostomy. The neonate and infant with PRS require care from
      multiple specialists including anesthesiology, plastic surgery, otolaryngology,
      speech pathology, gastroenterology, radiology, and neonatology. The
      anesthesiologist involved in the care of patients with PRS will interface with a
      multidisciplinary team in a variety of clinical settings. This perioperative
      review is a collaborative effort from multiple specialties including
      anesthesiology, plastic surgery, otolaryngology, and speech pathology. We will
      discuss the background and clinical presentation of patients with PRS, as well as
      some of the controversies regarding their care. 

PMID- 25046789
TI  - Evidence for the use of preoperative risk assessment scores in elective cranial
      neurosurgery: a systematic review of the literature.
AB  - BACKGROUND: Preoperative risk scores are designed to guide patient management by
      providing a means of predicting operative outcome. Several risk scores are used
      in neurosurgery, but studies on their clinical relevance are scarce. Therefore,
      it is not clear whether these risk scores are beneficial or helpful in predicting
      outcome after elective cranial neurosurgery. In this review, we summarize the
      current scientific evidence for using preoperative risk scores in elective
      cranial neurosurgery. METHODS: A systematic review of the MEDLINE, Embase, and
      PubMed databases in November 2013 yielded 25 relevant studies with a minimum of
      30 patients per study. The studies evaluated the value of the preoperative ASA
      physical status classification, the Karnofsky performance score (KPS), the
      Charlson comorbidity score, the modified Rankin Scale and the sex, KPS, ASA
      physical status classification, location, and edema (SKALE) score in assessing
      postoperative outcome in cranial neurosurgery. Surgery-related and nonsurgical
      complications were assessed separately whenever reported in the original article.
      For this purpose, the studies were placed into 4 categories based on the reported
      outcome: surgery-related outcome, nonsurgical outcome, morbidity, and mortality.
      The Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines
      for systematic reviews were followed. RESULTS: KPS has the strongest support in
      the literature for predicting surgery-related outcomes. There is no strong
      support in the literature for the use of any preoperative scores in predicting
      nonsurgical outcomes after elective craniotomies. KPS and ASA physical status
      classification seem to predict early (<= 30-day) morbidity of intracranial tumor
      patients. The Charlson comorbidity score may be applicable in predicting
      mortality of elective intracranial aneurysm patients. Only 4 studies were
      prospective in design. CONCLUSIONS: Large prospective studies are needed to
      validate the use of the reviewed risk scores in elective cranial neurosurgery. It
      appears, however, that the patient's preoperative physical and functional status
      can be used to predict the short- and long-term outcome in elective cranial
      neurosurgery.

PMID- 25046790
TI  - Sacroiliac joint radiofrequency ablation with a multilesion probe: a case series
      of 60 patients.
AB  - This retrospective case series of patients with refractory sacroiliac joint (SIJ)
      pain presents our first 77 SIJ radiofrequency ablation (RFA) procedures performed
      with a multilesion probe. Of these, 16 (20.8%) provided no relief; 55 (71.4%)
      provided >50% pain relief at 6 weeks; 42 (54.5%, 95% confidence interval, 42.8%
      65.8%) provided >50% pain relief at 6 months; and 12 (15.6%) continued to provide
      >50% pain relief at 1 year. These results compare favorably to those published
      using other RFA techniques. In conclusion, more than half of our patients with
      refractory SIJ pain received some pain relief for at least 6 months after RFA. 

PMID- 25046791
TI  - Risk of perioperative torsade de pointes in patients with poorly controlled
      diabetes mellitus.

PMID- 25046793
TI  - Tranexamic acid: more than inhibition of fibrinolysis?

PMID- 25046792
TI  - Random errors and misclassification bias.

PMID- 25046794
TI  - In response.

PMID- 25046795
TI  - Monochorionic twin pregnancy complicated by right ventricular outflow tract
      obstruction (RVOTO) of one fetus without proof of a twin-twin transfusion
      syndrome.

PMID- 25046796
TI  - The effect of hypogonadism and testosterone-enhancing therapy on alkaline
      phosphatase and bone mineral density.
AB  - OBJECTIVE: To evaluate the relationship of testosterone-enhancing therapy on
      alkaline phosphatase (AP) in relation to bone mineral density (BMD) in
      hypogonadal men. PATIENTS AND METHODS: Retrospective review of 140 men with
      testosterone levels of <350 ng/dL undergoing testosterone-enhancing therapy and
      followed for 2 years. Follicle-stimulating hormone, luteinising hormone, free
      testosterone, total testosterone, sex hormone binding globulin, calcium, AP,
      vitamin D, parathyroid hormone, and dual-energy X-ray absorptiometry (DEXA) scans
      were analysed. A subgroup of 36 men with one DEXA scan before and one DEXA 2
      years after initiating treatment was performed. RESULTS: Analysis of the
      relationship between testosterone and AP at initiation of therapy using stiff
      linear splines suggested that bone turnover occurs at total testosterone levels
      of <250 ng/dL. In men with testosterone levels of <250 ng/dL, there was a
      negative correlation between testosterone and AP (R(2) = -0.347, P < 0.001), and
      no correlation when testosterone levels were between 250 and 350 ng/dL. In the
      subgroup analysis, the mean (sd) testosterone level was 264 (103) ng/dL initially
      and 701 (245), 539 (292), and 338 (189) ng/dL at 6, 12, and 24 months,
      respectively. AP decreased from a mean (sd) of 87 (38) U/L to 57 (12) U/L (P =
      0.015), 60 (17) U/L (P < 0.001), and 55 (10) U/L (P = 0.03) at 6, 12, and 24
      months, respectively. The BMD increased by a mean (sd) of 20 (39)% (P = 0.003) on
      DEXA. CONCLUSION: In hypogonadal men, the decrease in AP is associated with an
      increase in BMD on DEXA testing. This result suggests the use of AP as a marker
      of response to therapy.

PMID- 25046797
TI  - Wood nitrogen concentrations in tropical trees: phylogenetic patterns and
      ecological correlates.
AB  - In tropical and temperate trees, wood chemical traits are hypothesized to covary
      with species' life-history strategy along a 'wood economics spectrum' (WES), but
      evidence supporting these expected patterns remains scarce. Due to its role in
      nutrient storage, we hypothesize that wood nitrogen (N) concentration will covary
      along the WES, being higher in slow-growing species with high wood density (WD),
      and lower in fast-growing species with low WD. In order to test this hypothesis
      we quantified wood N concentrations in 59 Panamanian hardwood species, and used
      this dataset to examine ecological correlates and phylogenetic patterns of wood
      N. Wood N varied > 14-fold among species between 0.04 and 0.59%; closely related
      species were more similar in wood N than expected by chance. Wood N was
      positively correlated with WD, and negatively correlated with log-transformed
      relative growth rates, although these relationships were relatively weak. We
      found evidence for co-evolution between wood N and both WD and log-transformed
      mortality rates. Our study provides evidence that wood N covaries with tree life
      history parameters, and that these patterns consistently co-evolve in tropical
      hardwoods. These results provide some support for the hypothesized WES, and
      suggest that wood is an increasingly important N pool through tropical forest
      succession.

PMID- 25046798
TI  - Mapping a plasmonic hologram with photosensitive polymer films: standing versus
      propagating waves.
AB  - We use a photosensitive layer containing azobenzene moieties to map near-field
      intensity patterns in the vicinity of nanogrids fabricated within a thin silver
      layer. It is known that azobenzene containing films deform permanently during
      irradiation, following the pattern of the field intensity. The photosensitive
      material reacts only to stationary waves whose intensity patterns do not change
      in time. In this study, we have found a periodic deformation above the silver
      film outside the nanostructure, even if the latter consists of just one groove.
      This is in contradiction to the widely accepted viewpoint that propagating
      surface plasmon modes dominate outside nanogrids. We explain our observation
      based on an electromagnetic hologram formed by the constructive interference
      between a propagating surface plasmon wave and the incident light. This hologram
      contains a stationary intensity and polarization grating that even appears in the
      absence of the polymer layer. 

PMID- 25046799
TI  - Enhanced optical output power of InGaN/GaN vertical light-emitting diodes by ZnO
      nanorods on plasma-treated N-face GaN.
AB  - Light-emitting diodes (LEDs) play an important role as a formidable contender for
      next-generation lighting sources and rapidly replace conventional lighting
      sources. In this report, the growth of high density inclined ZnO nanorods (NRs)
      on the N-face n-GaN surface for high efficiency vertical light-emitting diodes
      (VLEDs) is demonstrated based on oxygen plasma pretreatment and hydrothermal
      growth. Surface modification by oxygen plasma pretreatment efficiently produces
      GaOx nanoparticles on the N-face n-GaN surface and they play an important role in
      the hydrothermal growth of dense and inclined ZnO NRs. The optical output power
      of ZnO NR VLEDs following oxygen plasma pretreatment is strongly enhanced by a
      factor of 3.25 at an injection current of 350 mA, compared to that of planar
      VLEDs. The large enhancement of optical power is attributed to the dense ZnO NR
      layer which efficiently reduces the total internal reflection and enhances the
      waveguide effect in ZnO NRs. 

PMID- 25046800
TI  - Decreased atmospheric sulfur deposition across the Southeastern U.S.: when will
      watersheds release stored sulfate?
AB  - Emissions of sulfur dioxide (SO2) to the atmosphere lead to atmospheric
      deposition of sulfate (SO4(2-)), which is the dominant strong acid anion causing
      acidification of surface waters and soils in the eastern United States. Since
      passage of the Clean Air Act and its Amendments, atmospheric deposition of SO2 in
      this region has declined by over 80%, but few corresponding decreases in
      streamwater SO4(2-) concentrations have been observed in unglaciated watersheds.
      We calculated SO4(2-) mass balances for 27 forested, unglaciated watersheds from
      Pennsylvania to Georgia, by using total atmospheric deposition (wet plus dry) as
      input. Many of these watersheds still retain SO4(2-), unlike their counterparts
      in the northeastern U.S. and southern Canada. Our analysis showed that many of
      these watersheds should convert from retaining to releasing SO4(2-) over the next
      two decades. The specific years when the watersheds crossover from retaining to
      releasing SO4(2-) correspond to a general geographical pattern of later net
      watershed release from north to south. The single most important variable that
      explained the crossover year was the runoff ratio, defined as the ratio of annual
      mean stream discharge to precipitation. Percent clay content and mean soil depth
      were secondary factors in predicting crossover year. The conversion of watersheds
      from net SO4(2-) retention to release anticipates more widespread reductions in
      streamwater SO4(2-) concentrations in this region. 

PMID- 25046801
TI  - Organocatalytic enantioselective Pictet-Spengler reactions for the syntheses of 1
      substituted 1,2,3,4-tetrahydroisoquinolines.
AB  - A series of 1-substituted 1,2,3,4-tetrahydroisoquinolines was prepared from N-(o
      nitrophenylsulfenyl)phenylethylamines through BINOL-phosphoric acid [(R)-TRIP]
      catalyzed asymmetric Pictet-Spengler reactions. The sulfenamide moiety is crucial
      for the rate and enantioselectivity of the iminium ion cyclization and the
      products are readily recrystallized to high enantiomeric purity. Using this
      methodology we synthesized the natural products (R)-crispine A, (R)-calycotomine
      and (R)-colchietine, the synthetic drug (R)-almorexant and the (S)-enantiomer of
      a biologically active (R)-AMPA-antagonist. 

PMID- 25046802
TI  - Impact of the degree of ethoxylation of the ethoxylated polysorbate nonionic
      surfactant on the surface self-assembly of hydrophobin-ethoxylated polysorbate
      surfactant mixtures.
AB  - Neutron reflectivity measurements have been used to study the surface adsorption
      of the polyethylene sorbitan monostearate surfactant, with degrees of
      ethoxylation varying from 3 to 20 ethylene oxide groups, with the globular
      protein hydrophobin. The surface interaction between the ethoxylated polysorbate
      nonionic surfactants and the hydrophobin results in self-assembly at the air
      solution interface in the form of a well-defined layered surface structure. The
      surface interaction arises from a combination of the hydrophobic interaction
      between the surfactant alkyl chain and the hydrophobic patch on the surface of
      the hydrophobin, and the hydrophilic interaction between the ethoxylated sorbitan
      headgroup and the hydrophilic regions on the surface of the hydrophobin. The
      results presented show that varying the degree of ethoxylation of the polysorbate
      surfactant changes the interaction between the surfactant and the hydrophobin and
      the packing, and hence the evolution in the resulting surface structure. The
      optimal degree of ethoxylation for multilayer formation is over a broad range,
      from of order 6 to 17 ethylene oxide groups, and for degrees of ethoxylation of 3
      and 20 only monolayer adsorption of either the surfactant or the hydrophobin is
      observed. 

PMID- 25046803
TI  - Solid-phase covalent immobilization of upconverting nanoparticles for biosensing
      by luminescence resonance energy transfer.
AB  - Monodisperse water-soluble upconverting nanoparticles (UCNPs) were immobilized
      onto modified glass substrates for development of biosensing surfaces that
      operated using luminescence resonance energy transfer (LRET). Amine modified
      UCNPs were prepared from oleic acid capped UCNPs by ligand exchange using o
      phosphorylethanolamine (PEA). PEA-UCNPs were covalently immobilized on aldehyde
      functionalized coverslips. Environmental scanning electron microscopy (ESEM)
      images indicated a homogeneous distribution of UCNPs on surfaces with a high
      immobilization density of approximately 1.3 * 10(11) UCNP cm(-2). This is the
      first account of covalent immobilization of UCNPs for bioassay and biosensor
      development where the density is on par with the high immobilization densities
      reported for other types of nanoparticles. The functionality and stability of the
      immobilized NPs were demonstrated by examining an LRET-based bioassay. The well
      known sandwich assay for the detection of thrombin was selected as a model in
      which UCNPs were used as donors and quantum dots (QDs) as acceptors. The closely
      packed UCNPs on the glass surface showed a 2.5-fold enhancement in assay
      sensitivity compared to less-densely packed surfaces. In addition, a 1.5-fold
      enhancement in energy transfer efficiency was shown for solid-phase compared to
      solution-phase LRET. 

PMID- 25046804
TI  - Activin and NADPH-oxidase in preeclampsia: insights from in vitro and murine
      studies.
AB  - OBJECTIVE: Clinical management of preeclampsia has remained unchanged for almost
      5 decades. We now understand that maternal endothelial dysfunction likely arises
      because of placenta-derived vasoactive factors. Activin A is one such
      antiangiogenic factor that is released by the placenta and that is elevated in
      maternal serum in women with preeclampsia. Whether activin has a role in the
      pathogenesis of preeclampsia is not known. STUDY DESIGN: To assess the effects of
      activin on endothelial cell function, we cultured human umbilical vein
      endothelial cells in the presence of activin or serum from normal pregnant women
      or pregnant women with preeclampsia, with or without follistatin, a functional
      activin antagonist or apocynin, a NADPH oxidase (Nox2) inhibitor. We also
      administered activin to pregnant C57Bl6 mice, with or without apocynin, and
      studied maternal and fetal outcomes. Last, we assessed endothelial cell Nox2 and
      nitric oxide synthase expression in normal pregnant women and pregnant women with
      preeclampsia. RESULTS: Activin and preeclamptic serum induced endothelial cell
      oxidative stress by Nox2 up-regulation and endothelial cell dysfunction, which
      are effects that are mitigated by either follistatin or apocynin. The
      administration of activin to pregnant mice induced endothelial oxidative stress,
      hypertension, proteinuria, fetal growth restriction, and preterm littering.
      Apocynin prevented all of these effects. Compared with normal pregnant women,
      women with preeclampsia had increased endothelial Nox2 expression. CONCLUSION: An
      activin-Nox2 pathway is a likely link between an injured placenta, endothelial
      dysfunction, and preeclampsia. This offers opportunities that are not novel
      therapeutic approaches to preeclampsia.

PMID- 25046805
TI  - Association of short-term bleeding and cramping patterns with long-acting
      reversible contraceptive method satisfaction.
AB  - OBJECTIVE: We sought to examine the short-term (3- and 6-month), self-reported
      bleeding and cramping patterns with intrauterine devices (IUDs) and the
      contraceptive implant, and the association of these symptoms with method
      satisfaction. STUDY DESIGN: We analyzed 3- and 6-month survey data from IUD and
      implant users in the Contraceptive CHOICE Project, a prospective cohort study.
      Participants who received a long-acting reversible contraceptive (LARC) method
      (levonorgestrel-releasing intrauterine system [LNG-IUS], copper IUD, or the
      etonogestrel implant) and completed their 3- and 6-month surveys were included.
      Univariable and multivariable analyses were performed to examine the association
      of bleeding and cramping patterns with short-term satisfaction. RESULTS: Our
      analytic sample included 5011 Contraceptive CHOICE Project participants: 3001 LNG
      IUS users, 826 copper IUD users, and 1184 implant users. At 3 months, >65% of LNG
      IUS and implant users reported no change or decreased cramping, while 63% of
      copper IUD users reported increased menstrual cramping. Lighter bleeding was
      reported by 67% of LNG-IUS users, 58% of implant users, and 8% of copper IUD
      users. Satisfaction of all LARC methods was high (>=90%). LARC users with
      increased menstrual cramping (relative risk adjusted [RRadj], 0.78; 95%
      confidence interval [CI], 0.72-0.85), heavier bleeding (RRadj, 0.83; 95% CI, 0.76
      0.92), and increased bleeding frequency (RRadj, 0.73; 95% CI, 0.67-0.80) were
      less likely to report being very satisfied at 6 months. CONCLUSION: Regardless of
      the LARC method, satisfaction at 3 and 6 months is very high. Changes in self
      reported bleeding and cramping are associated with short-term LARC satisfaction.

PMID- 25046807
TI  - A retrospective analysis of the effect of salpingectomy on serum antiMullerian
      hormone level and ovarian reserve.
AB  - OBJECTIVE: To determine whether previous salpingectomy is associated with serum
      antiMullerian hormone (AMH) level and ovarian reserve in women under 40 years
      presenting for in vitro fertilization and embryo transfer. STUDY DESIGN: We
      retrospectively compared serum AMH levels measured on the ovulation induction
      initiation day in patients with unilateral salpingectomy, bilateral
      salpingectomy, and no tubal surgery, and examined the relationship with length of
      time after surgery and in vitro fertilization and embryo transfer parameters.
      RESULTS: A total of 198 women were included; 83 received unilateral
      salpingectomy, 41 bilateral salpingectomy, and 74 no tubal surgery. The baseline
      characteristics of the groups were similar. The mean AMH level was significantly
      higher in women without tubal surgery as compared with those with bilateral
      salpingectomy (183.48 vs 127.11 fmol/mL; P <= .037). The mean follicle
      stimulation hormone level was significantly lower in women without surgery as
      compared with those with bilateral salpingectomy (7.85 vs 9.13 mIU/mL; P = .048).
      No significant differences in duration of gonadotropin therapy, amount of
      gonadotropin used, estradiol level on the human chorionic gonadotropin injection
      day, thickness of the endometrium, number of oocytes retrieved, number of 2
      pronuclei, viable embryos, and good quality embryos were found between the 3
      groups. AMH level was not correlated with the number of oocytes or age in women
      that had undergone unilateral or bilateral salpingectomy. CONCLUSION:
      Salpingectomy is associated with decreased AMH level and increased follicle
      stimulation hormone in women seeking in vitro fertilization, though AMH level is
      not correlated with the number of oocytes retrieved in patients that have
      undergone unilateral or bilateral salpingectomy. These results suggest that
      salpingectomy is associated with decreased ovarian reserve.

PMID- 25046809
TI  - Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated
      with elevated bile acid levels.
AB  - OBJECTIVE: The primary aim of this study was to investigate the correlation
      between pregnancy outcome and bile acid (BA) levels in pregnancies that were
      affected by intrahepatic cholestasis of pregnancy (ICP). In addition,
      correlations between maternal and fetal BA levels were explored. STUDY DESIGN: We
      conducted a retrospective study that included women with pruritus and BA levels
      >=10 MUmol/L between January 2005 and August 2012 in 3 large hospitals in the
      Netherlands. The study group was divided in mild (10-39 MUmol/L), moderate (40-99
      MUmol/L), and severe (>=100 MUmol/L) ICP. Main outcome measures were spontaneous
      preterm birth, meconium-stained amniotic fluid, asphyxia, and perinatal death.
      Univariate and multivariate logistic regression analysis was used to study
      associations between BA levels and adverse outcome. RESULTS: A total of 215 women
      were included. Gestational age at diagnosis and gestational age at delivery were
      significantly lower in the severe, as compared with the mild, ICP group (P <
      .001). Spontaneous preterm birth (19.0%), meconium-stained fluid (47.6%), and
      perinatal death (9.5%) occurred significantly more often in cases with severe
      ICP. Higher BA levels were associated significantly with spontaneous preterm
      birth (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 1.03-1.28),
      meconium-stained amniotic fluid (aOR, 1.15; 95% CI, 1.06-1.25), and perinatal
      death (aOR, 1.26; 95% CI, 1.01-1.57). Maternal BA levels at diagnosis and at
      delivery were correlated positively with umbilical cord blood BA levels (P = .006
      and .012, respectively). CONCLUSION: Severe ICP is associated with adverse
      pregnancy outcome. Levels of BA correlate between mother and fetus.

PMID- 25046811
TI  - Use of a uniconcave balloon in emergency cerclage.
AB  - Pushing bulging fetal membranes back into the uterine cavity effectively without
      rupture of fetal membranes during emergency cerclage is a concern to
      obstetricians. We have developed a new uniconcave balloon device for
      repositioning fetal membranes into the uterus during emergency cerclage. Our
      technique can be accomplished easily with few complications. 

PMID- 25046810
TI  - The effect of pessaries on the vaginal microenvironment.
AB  - OBJECTIVE: The objective of the study was to evaluate the differences in vaginal
      culture, microscopy, and Gram stain between postmenopausal women who wear
      pessaries and those who do not to explain pessary-related, bothersome vaginal
      discharge. STUDY DESIGN: Postmenopausal women not using exogenous estrogen who
      had either been wearing a pessary for at least 3 months or who were undergoing
      their first pessary fittings were approached for enrollment. Symptoms were
      assessed, and vaginal fluid was collected for culture, microscopy, and Gram
      stain. A cross-sectional analysis was performed, comparing the new and return
      pessary wearers. The new pessary users were also sampled at 2 weeks, 3 months,
      and 6 months after fitting. RESULTS: Women who wore pessaries were more likely to
      be bothered by discharge (30.0% vs 2.1%, P < .001). They were also more likely to
      show microscopic evidence of vaginal inflammation and vaginitis. Prospective data
      showed that these changes developed during the first 2 weeks of pessary use.
      Aerobic and anaerobic organisms were nearly identical in women with and without
      bothersome vaginal discharge in the cross-sectional analysis and at all time
      points in the prospective analysis. CONCLUSION: Pessary-related, bothersome
      vaginal discharge develops early and may be due to an inflammatory process in the
      vagina.

PMID- 25046806
TI  - Antenatal magnesium sulfate exposure and acute cardiorespiratory events in
      preterm infants.
AB  - OBJECTIVE: Antenatal magnesium (anteMg) is used for various obstetric indications
      including fetal neuroprotection. Infants exposed to anteMg may be at risk for
      respiratory depression and delivery room (DR) resuscitation. The study objective
      was to compare the risk of acute cardiorespiratory events among preterm infants
      who were and were not exposed to anteMg. STUDY DESIGN: This was a retrospective
      analysis of prospective data collected in the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development Neonatal Research Network's
      Generic Database from April 1, 2011, through March 31, 2012. The primary outcome
      was DR intubation or respiratory support at birth or on day 1 of life. Secondary
      outcomes were invasive mechanical ventilation, hypotension treatment, neonatal
      morbidities, and mortality. Logistic regression analysis evaluated the risk of
      primary outcome after adjustment for covariates. RESULTS: We evaluated 1544
      infants <29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed
      group). Mothers in the anteMg group were more likely to have higher education,
      pregnancy-induced hypertension, and antenatal corticosteroids, while their
      infants were younger in gestation and weighed less (P < .05). The primary outcome
      (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar
      between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive
      mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in
      the anteMg group. CONCLUSION: Among preterm infants age <29 weeks' gestation,
      anteMg exposure was not associated with an increase in cardiorespiratory events
      in the early newborn period. The safety of anteMg as measured by the need for DR
      intubation or respiratory support on day 1 of life was comparable between groups.

PMID- 25046812
TI  - A geographical comparison of chlorinated, brominated and fluorinated compounds in
      seabirds breeding in the eastern Canadian Arctic.
AB  - A suite of chlorinated, brominated and fluorinated organic contaminants were
      measured in livers of adult thick-billed murres (Uria lomvia) and northern
      fulmars (Fulmarus glacialis) from several locations in the eastern Canadian
      Arctic during 2007-2008. Thick-billed murres were collected from five colonies
      (Coats Island, Digges Island, Akpatok Island, Prince Leopold Island, Minarets)
      and northern fulmars from two colonies (Prince Leopold Island, Minarets). Legacy
      organochlorines (e.g. PCBs, DDT, chlorobenzenes, chlordanes) and perfluorooctane
      sulfonate (PFOS) dominated the compositional profiles of the measured halogenated
      compounds in the livers of both species at all colonies. Among the murre colonies
      sampled, Prince Leopold Island birds generally had the highest mean
      concentrations of organochlorines, whereas the highest mean concentration of sum
      (Sigma) polybrominated diphenyl ethers (PBDEs) was found at the Minarets and the
      lowest at Prince Leopold Island. PBDEs were detected in only a few fulmar livers
      from the Minarets and in none of the fulmar livers from Prince Leopold Island.
      Mean PFOS concentrations were highest in both murre and fulmar livers at Prince
      Leopold Island. PFOS was approximately two orders of magnitude higher than the
      mean sum (Sigma) perfluorinated carboxylate (PFCA) concentration in both species
      and at all colonies. The reasons for inter-colony and inter-species differences
      in contaminant liver levels are probably variable and complex, and likely reflect
      differences in contaminant transport and exposure pathways, as well as
      differences among colonies in their diets and overwintering areas. To our
      knowledge, this is the first spatial assessment of PBDEs, PFCAs and PFOS in
      seabirds from the Canadian Arctic. 

PMID- 25046813
TI  - Risk-benefit of consuming Lake Erie fish.
AB  - BACKGROUND: Consumption of fish is promoted as a healthy way to obtain essential
      fatty acids (EFA) in the diet, yet the risk of ingesting harmful contaminants
      remains a concern. A recent study concluded that the risk-benefit of consuming
      fish from the North American Laurentian Great Lakes, which sustain important
      commercial and recreational fisheries, is currently unclear. We report the fatty
      acid (FA) content in skin-off fillets of fifteen fish species from Lake Erie and
      assess whether recommended dietary requirements for two EFA (EPA and DHA) can be
      met by safely consuming Lake Erie fishes, as an example of a risk-benefit
      analysis. METHODS: A total of 146 samples were analyzed for FA and contaminant
      content. A simulated fish consumption advisory (maximum recommended number of
      meals per month, up to 32) was calculated for each sample, and used to calculate
      the maximum amount of EPA+DHA that would be consumed if the consumption advisory
      was followed. RESULTS: All fifteen species had nutritionally desirable PUFA:SAFA
      (>0.4) and n-3:n-6 (>1). Large, fatty species had the highest EPA+DHA content,
      but had the most restrictive consumption advisories due to high PCB
      concentrations. To minimize contaminant exposure while maximizing EPA+DHA intake,
      consumers should consider small lake whitefish and lake trout, small panfish
      species, and/or walleye. However, very few species had an EPA+DHA content
      sufficient to safely meet the highest dietary guidelines while following
      advisories. CONCLUSIONS: Consumption of certain Lake Erie fish, an important
      recreational and commercial fishery, within the limits of our simulated fish
      consumption advisories, can be a good supplemental source of beneficial n-3 long
      chain PUFA.

PMID- 25046814
TI  - Cadmium exposure and neuropsychological development in school children in
      southwestern Spain.
AB  - This study assessed the association between cadmium exposure and
      neuropsychological development in children from a region with high industrial and
      mining activities in southwestern Spain. We conducted a cross-sectional study
      with 261 children aged 6-9 years between January and March 2012. Cadmium exposure
      was measured in urine and hair of children, and neuropsychological development
      was assessed with the Wechsler Intelligence Scale for Children-Fourth Edition
      (WISC-IV) and with three computerized tests from the Behavioral Assessment and
      Research System (BARS): Reaction Time Test (RTT), Continuous Performance Test
      (CPT) and Selective Attention Test (SAT). Multivariate linear regression models,
      adjusted for potential confounders, were used to estimate the association between
      neuropsychological development and cadmium exposure measured in urine and hair
      samples. Geometric means of urine and hair cadmium levels were 0.75 MUg/g
      creatinine and 0.01 MUg/g, respectively. We observed that doubling of levels of
      cadmium in urine was associated with a reduction of two points (95% CI: -3.8 to 
      0.4) in the Full-Scale intelligence quotient (IQ) in boys. By domains,
      association was statistically significant for Verbal Comprehension (beta=-2.0;
      p=0.04) and close to the significance level for Perceptual Reasoning (beta=-1.8;
      p=0.06). Among girls, only Verbal Comprehension showed suggestive associations
      with cadmium exposure (beta=-1.7; p=0.06). Cadmium exposure is associated with
      cognitive delays in boys in our region. Our results provide additional evidence
      of the neurotoxic effect of low-level postnatal cadmium exposure among children,
      and support the hypothesis of differences between sexes in the neurotoxic effect
      of metals on children.

PMID- 25046815
TI  - The extremely low-frequency magnetic field exposure differently affects the AMPAR
      and NMDAR subunit expressions in the hippocampus, entorhinal cortex and
      prefrontal cortex without effects on the rat spatial learning and memory.
AB  - In the present study, we investigated the effects of chronic exposure (14 and 28
      days) to a 50 Hz, 0.5 mT extremely low-frequency magnetic field (ELF-MF) on the
      NMDAR and AMPAR subunit expressions and rat spatial learning and memory. Using
      the Western blotting method, we found ELF-MF exposure specifically decreased the
      expressions of GluA2 in the EC post 28 day exposure and GluA3 of AMPAR subunits
      in the PFC after 14 day exposure, while it did not affect the AMPAR subunit
      expression in the hippocampus at both time points. As for NMDAR subunits, 14 day
      ELF-MF exposure significantly increased the levels of GluN2A and GluN2B in the
      hippocampus. Moreover, the levels of GluN1 and GluN2A were enhanced in the EC and
      PFC after two weeks of ELF-MF exposure. Interestingly, 28 day ELF-MF exposure
      induced a different expression pattern for NMDAR subunits. The increased GluN2A
      expression observed at 14 day post ELF-MF exposure was recovered after prolonged
      exposure in the hippocampus and PFC. In the EC, the increased expression of GluN1
      achieved to control level and, specifically, a decrease in GluN2A level was
      observed. Surprisingly, neither 14 nor 28 day ELF-MF did affect the rat spatial
      reference memory as assessed by water maze. These results indicate that the
      dynamic and brain-region specific changes in ionotropic glutamate receptor
      expression induced by ELF-MF are insufficient to influence the rat spatial
      learning ability.

PMID- 25046816
TI  - Gold nanoparticles tune the activity of laccase in anionic reverse micelles.
AB  - The interfacial property of reverse micelles is an important factor affecting the
      catalytic activity of enzymes hosted in the micelles. In this article, the effect
      of gold nanoparticles (GNPs) on the catalytic activity of laccase (non-surface
      active enzyme) and the related mechanism are reported. It was found that laccase
      activity was dependent on the size of the particle and its concentration as well
      as on the water content and the concentration of AOT. It was shown that there
      existed several types of micelles in the present reverse micellar system in the
      presence of GNPs. The population of the various micelles depended on the
      concentrations of both GNPs and AOT. Fluorescence and circular dichroism spectra
      of laccase at different water contents and GNP concentrations indicated that the
      conformation of laccase and its activity were tuned by GNPs via changing the
      structure of the reverse micelles. Analysis showed that changes in the thickness
      of the water layer (Lw) and in the apparent occupied area of individual AOT
      molecules (AAOT) caused by GNPs were the main parameters affecting the activity
      of laccase. The present work extends and deepens the understanding of the tuning
      mechanism of GNPs on enzymatic performance in reverse micelles and provides
      guidance for rational design of the optimal microenvironment of laccase. 

PMID- 25046817
TI  - A form-fitted three channel (31) P, two channel (1) H transceiver coil array for
      calf muscle studies at 7 T.
AB  - PURPOSE: To enhance sensitivity and coverage for calf muscle studies, a novel,
      form-fitted, three-channel phosphorus-31 ((31) P), two-channel proton ((1) H)
      transceiver coil array for 7 T MR imaging and spectroscopy is presented. METHODS:
      Electromagnetic simulations employing individually generated voxel models were
      performed to design a coil array for studying nonpathological muscle metabolism.
      Static phase combinations of the coil elements' transmit fields were optimized
      based on homogeneity and efficiency for several voxel models. The best-performing
      design was built and tested both on phantoms and in vivo. RESULTS: Simulations
      revealed that a shared conductor array for (31) P provides more robust
      interelement decoupling and better homogeneity than an overlap array in this
      configuration. A static B1 (+) shim setting that suited various calf anatomies
      was identified and implemented. Simulations showed that the (31) P array provides
      signal-to-noise ratio (SNR) benefits over a single loop and a birdcage coil of
      equal radius by factors of 3.2 and 2.6 in the gastrocnemius and by 2.5 and 2.0 in
      the soleus muscle. CONCLUSION: The performance of the coil in terms of B1 (+) and
      achievable SNR allows for spatially localized dynamic (31) P spectroscopy studies
      in the human calf. The associated higher specificity with respect to nonlocalized
      measurements permits distinguishing the functional responses of different
      muscles.

PMID- 25046818
TI  - Statistical simulation of SAR variability with geometric and tissue property
      changes by using the unscented transform.
AB  - PURPOSE: The local specific absorption rate (SAR) is critical to the safety of
      radio frequency transmit coils. A statistical simulation approach is introduced
      to address the local SAR variability related to tissue property and geometric
      variations. METHODS: The local SAR is modeled as the output of a nonlinear
      transformation with factors that may affect its value being treated as random
      input variables. Instead of using the Monte Carlo method with a large number of
      sample points, the unscented transform is applied with a small set of
      deterministic sample points. A sensitivity analysis is further performed to
      determine the significance of each input variable. Electromagnetic simulations
      are carried out by the finite-difference time-domain method implemented on
      graphic processing unit. RESULTS: The local SAR variability of a 7 Tesla square
      loop coil for spine imaging and a 16-element brain imaging array as the result of
      tissue property and geometric changes were examined respectively. SAR limits were
      determined based on their means and standard deviations. CONCLUSION: The proposed
      approach is efficient and general for the study of local SAR variability.

PMID- 25046820
TI  - The NO/sGC/PKG signaling pathway in the NAc shell is necessary for the
      acquisition of morphine-induced place preference.
AB  - There is evidence that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP
      dependent protein kinase (PKG) signaling pathway in the basal lateral amygdala
      and hippocampus plays a key role in memory processing, but it is not known if
      this NO signaling pathway in the nucleus accumbens (Gomes et al., 2006), a known
      pivotal region in reward memory, is essential for drug-associated reward memory.
      We therefore investigated the effect of the NO/sGC/PKG signaling pathway in the
      nucleus accumbens (NAc) on morphine-induced conditioned place preference (CPP).
      Results showed that a preconditioning microinjection of the NO synthase (NOS)
      inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) into the NAc shell, but
      not into the core, significantly blocked the acquisition of morphine CPP. The
      blockage effect of L-NAME on the acquisition of CPP was imitated by the neuronal
      NOS inhibitor 7-nitroindazole, 3-bromo-, sodium salt (7-NI), the sGC inhibitor 1H
      [1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), and the PKG inhibitor Rp-8Br
      PET-cGMPS. The 7-NI- or ODQ-induced effect was reversed by premicroinjection of
      the sGC activator YC-1 or the PKG activator 8-Br-cGMP in the NAc shell. However,
      microinfusion of 7-NI, ODQ, or Rp-8Br-PET-cGMPS into the NAc shell or the core
      had no effect on the expression of morphine CPP. These findings indicate that the
      NO/sGC/PKG signaling pathway in the NAc shell is critical for the acquisition of
      morphine-induced place preference, whereas the same signaling pathway in the NAc
      shell or core is not involved in the retrieval of morphine-induced place
      preference.

PMID- 25046819
TI  - Biomarkers distinguish apoptotic and necrotic cell death during hepatic
      ischemia/reperfusion injury in mice.
AB  - Hepatic ischemia/reperfusion (IRP) injury is a significant clinical problem
      during tumor-resection surgery (Pringle maneuver) and liver transplantation.
      However, the relative contribution of necrotic and apoptotic cell death to the
      overall liver injury is still controversial. To address this important issue with
      a standard murine model of hepatic IRP injury, plasma biomarkers of necrotic cell
      death such as micro-RNA 122, full-length cytokeratin 18 (FK18), and high-mobility
      group box 1 (HMGB1) protein and plasma biomarkers of apoptosis such as plasma
      caspase-3 activity and caspase-cleaved fragment of cytokeratin 18 (CK18) coupled
      with markers of inflammation (hyperacetylated HMGB1) were compared by
      histological features in hematoxylin and eosin-stained and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      (TUNEL)-stained liver sections. After 45 minutes of hepatic ischemia and 1 to 24
      hours of reperfusion, all necrosis markers increased dramatically in plasma by 40
      to >10,000-fold over the baseline with a time course similar to that of alanine
      aminotransferase. These data correlated well with histological characteristics of
      necrosis. Within the area of necrosis, most cells were TUNEL positive; initially
      (<=3 hours of reperfusion), the staining was restricted to nuclei, but it later
      spread to the cytosol, and this is characteristic of karyorrhexis during necrotic
      cell death. In contrast, the lack of morphological evidence of apoptotic cell
      death and relevant caspase-3 activity in the postischemic liver correlated well
      with the absence of caspase-3 activity and CK18 (except for a minor increase at 3
      hours of reperfusion) in plasma. A quantitative comparison of FK18 (necrosis) and
      CK18 (apoptosis) release indicated dominant cell death by necrosis during IRP and
      only a temporary and very minor degree of apoptosis. These data suggest that the
      focus of future research should be the elucidation of necrotic signaling
      mechanisms to identify relevant targets, which may be used to attenuate hepatic
      IRP injury.

PMID- 25046821
TI  - Redefining the vascular anatomy of the peroneus brevis muscle flap.
AB  - The peroneus brevis flap can be used as either proximally or distally based flap
      for coverage of small to medium-sized defects in the lower leg. The purpose of
      this study was to clarify the vascular anatomy of the peroneus brevis muscle. An
      anatomical dissection was performed on 17 fixed adult cadaver lower legs.
      Altogether, 87 segmental branches (mean 5.1 +/- 1.6 per leg) either from the
      fibular or anterior tibial artery to the muscle were identified. Sixty-two were
      branches from the fibular artery (mean 3.4 +/- 1.1 per fibular artery), whereas
      25 (mean 1.4 +/- 0.9 per anterior tibial artery) originated from the anterior
      tibial artery. The distance between the most distal vascular branch and the
      malleolar tip averaged 4.3 +/- 0.6 cm. An axial vascular bundle to the muscle
      could be identified in all cadavers; in one leg two axial supplying vessels were
      found. Their average length was 5.5 +/- 2.4 cm and the average arterial diameter
      was 1.1 +/- 0.5 mm, the average venous diameter was 1.54 +/- 0.7 mm. The constant
      blood supply to the peroneus brevis muscle by segmental branches from the fibular
      and tibial artery make this muscle a viable option for proximally or distally
      pedicled flap transfer. The location of the most proximal and distal branches to
      the muscle and conclusively the pivot points for flap transfer could be
      determined. Furthermore, a constant proximal axial vascular pedicle to the muscle
      may enlarge the clinical applications. Perfusion studies should be conducted to
      confirm these findings.

PMID- 25046822
TI  - Complete genome sequence of Salmonella enterica serovar Typhimurium VNP20009, a
      strain engineered for tumor targeting.
AB  - A mutagenized and genetically modified derivative of Salmonella enterica serovar
      Typhimurium 14028S, VNP20009 (ATCC 202165), is attenuated in host virulence and
      accumulates preferentially in tumors. Here, we report the complete genome of this
      anticancer therapy agent consisting of one chromosome and one virulence plasmid.
      The major genetic features that distinguish VNP20009 from its parental strain
      are: an engineered msbB deletion, a 3'-extension in pykA, a Tn10-caused 16.6-kbp
      inversion leading to the disruption of purM, a 108-kbp Suwwan deletion resulting
      in the loss of 128 genes, and 50 non-synonymous SNPs. 

PMID- 25046823
TI  - Cognitive deficits as an endophenotype for anorexia nervosa: an accepted fact or
      a need for re-examination?
AB  - OBJECTIVE: To investigate whether impaired set shifting and weak central
      coherence represent state or trait characteristics and, therefore, candidate
      endophenotypes of anorexia nervosa (AN). METHOD: Forty-nine individuals with
      lifetime AN (24 acutely unwell, 10 weight recovered, and 15 fully recovered) and
      43 healthy controls completed the Wisconsin Card Sorting Test (WCST), the
      Matching Familiar Figures Test, and the Rey Complex Figure Task measuring
      cognitive flexibility, local processing, and global processing, respectively.
      Participants also completed questionnaires assessing eating disorder, anxiety and
      depressive symptoms, obsessional traits, interpersonal functioning, and quality
      of life. Body mass index was calculated from height and weight measurements.
      RESULTS: Participants with lifetime AN demonstrated poorer set shifting ability
      than healthy controls as evidenced by a greater number of perseverative errors on
      the WCST. When participants were grouped according to illness status, only those
      in the two recovered groups demonstrated poorer set shifting ability than healthy
      controls while patients with acute AN performed comparably to all other groups.
      There were no significant differences between groups on measures of local and
      global processing. No relationship was found between specific clinical features
      of AN and cognitive performance. DISCUSSION: The results of this study are
      consistent with a global trend toward set shifting difficulties in patients with
      AN but do not support weak central coherence as a candidate endophenotype for AN.
      These findings have clinical implications in terms of treatment selection and
      planning, particularly in relation to the use of cognitive remediation therapy
      with patients with AN.

PMID- 25046824
TI  - High-pressure phase transition of cesium chloride and cesium bromide.
AB  - The high-symmetry cubic cesium chloride (CsCl) structure with a space group of
      Pm3-m (Z = 1) is one of the prototypical AB-type compounds, which is shared with
      cesium halides and many binary metallic alloys. The study of high-pressure
      evolution of the CsCl phase is of fundamental importance in helping to understand
      the structural sequence and principles of crystallography. Here, we have
      systematically investigated the high-pressure structural transition of cesium
      halides up to 200 GPa using an effective CALYPSO algorithm. Strikingly, we have
      predicted several thermodynamically favored high-pressure phases for cesium
      chloride and cesium bromide (CsBr). Further electronic calculations indicate that
      CsCl and CsBr become metallic via band-gap closure at strong compression. The
      current predictions have broad implications for other AB-type compounds that
      likely harbor similar novel high-pressure behavior.

PMID- 25046825
TI  - Treatment with ginseng total saponins improves the neurorestoration of rat after
      traumatic brain injury.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng, the root of Panax ginseng C.A. Meyer, is
      a traditional medicinal herb that has been widely used in Asia for the treatment
      of many diseases through its effects of reinforcing vitality, strengthening the
      bodily resistance to pathogenic factors, engendering body liquids and allaying
      thirst, relieving uneasiness of the body and mind and benefiting intelligence,
      reducing body weight and prolonging life. Ginsenosides are the most important
      biologically active substances in ginseng. Many reports have suggested that
      ginsenosides could exert prominent neuroprotective and neurotrophic effects,
      promote neural stem/progenitor cell (NSC) proliferation and promote neurite
      outgrowth and neuronal network formation. The present study aimed to investigate
      whether treatment with ginsenosides could facilitate NSC proliferation in the
      hippocampal formation after traumatic brain injury (TBI) and contribute to the
      recovery of neurological functions including learning and memory. MATERIALS AND
      METHODS: The modified Feeney's method was used to induce a TBI in rats. Ginseng
      total saponins (GTS) were treated intraperitoneally twice a day for 1 week after
      the TBI. The neurological functions, morphology of the hippocampus, expression of
      nerve growth-related factors and number of NSCs in the hippocampal formation
      ipsilateral to the trauma were determined. RESULTS: We determined 1) GTS (5-80
      mg/kg) treatment after a TBI improved the recovery of neurological functions,
      including learning and memory, and reduced cell loss in the hippocampal area. The
      effects of GTS at 20, 40, 60, and 80 mg/kg were better than the effects of GTS at
      5 and 10 mg/kg. 2) GTS treatment (20 mg/kg) after a TBI increased the expression
      of NGF, GDNF and NCAM, inhibited the expression of Nogo-A, Nogo-B, TN-C, and
      increased the number of BrdU/nestin positive NSCs in the hippocampal formation.
      CONCLUSIONS: GTS treatment in rats after a TBI alleviated the secondary brain
      injury and ameliorated the neurological functions with an effective dose limit of
      5-80 mg/kg. GTS regulated the expression of nerve growth-related factors and
      improved the proliferation of neural stem/progenitor cells, which might
      facilitate neural regeneration and tissue repair, and might contribute to the
      recovery of neurological functions, including learning and memory. These effects
      of GTS might provide a foundation for the use of ginseng as a medicinal herb to
      enhance intelligence, reduce the aging process and prolong life in the
      traditional medicine.

PMID- 25046826
TI  - Comparative pharmacokinetics of rhein in normal and loperamide-induced
      constipated rats and microarray analysis of drug-metabolizing genes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhein is a pharmacological active component found
      in Rheum palmatum L. that is the major herb of the San-Huang-Xie-Xin-Tang
      (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we
      have investigated the comparative pharmacokinetics of rhein in normal and
      constipated rats. Microarray analysis was used to explore whether drug
      metabolizing genes will be altered after SHXXT treatment. MATERIALS AND METHODS:
      The comparative pharmacokinetics of rhein in normal and loperamide-induced
      constipated rats was studied by liquid chromatography with electrospray
      ionization tandem mass spectrometry (LC-MS/MS). Gene expression profiling in drug
      metabolizing genes after SHXXT treatment was investigated by microarray analysis
      and real-time polymerase chain reaction (RT-PCR). RESULTS: A validated LC-MS/MS
      method was applied to investigate the comparative pharmacokinetics of rhein in
      normal and loperamide-induced constipated rats. The pharmacokinetic results
      demonstrate that the loperamide-induced constipation reduced the absorption of
      rhein. Cmax significantly reduced by 2.5-fold, the AUC decreased by 27.8%;
      however, the elimination half-life (t1/2) was prolonged by 1.6-fold. Tmax and
      mean residence time (MRT) were significantly prolonged by 2.8-fold, and 1.7-fold,
      respectively. The volume of distribution (Vss) increased by 2.2-fold. The data of
      microarray analysis on gene expression indicate that five drug-metabolizing
      genes, including Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly
      altered by the SHXXT (0.5 g/kg) treatment. CONCLUSION: The loperamide-induced
      constipation reduced the absorption of rhein. Since among the 25,338 genes
      analyzed, there were five genes significantly altered by SHXXT treatment. Thus,
      information on minor drug-metabolizing genes altered by SHXXT treatment indicates
      that SHXXT is relatively safe for clinical application.

PMID- 25046827
TI  - GC-MS method for determination and pharmacokinetic study of four phenylpropanoids
      in rat plasma after oral administration of the essential oil of Acorus
      tatarinowii Schott rhizomes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Acorus tatarinowii Schott (AT), belong to the
      family Araceae, is perennial herbaceous plant mainly present in China, Japan and
      India. The rhizomes of AT have been used as a famous traditional Chinese medicine
      for the treatment of central nervous system related diseases. AIM OF THE STUDY: A
      selective, accurate and sensitive method using gas chromatography-mass
      spectroscopy (GC-MS) for the simultaneous determination and pharmacokinetic study
      of beta-asarone, alpha-asarone, elemicin and cis-methyl isoeugenol in rat plasma
      was developed and validated. MATERIALS AND METHODS: The GC-MS system was operated
      under selected ion monitoring (SIM) mode. The samples were prepared by protein
      precipitation with acetonitrile after being spiked with an internal standard (1
      naphthol). The GC separation was achieved on a DB-1701 column (60 m * 0.25 mm ID,
      and 0.25 um film thickness). RESULTS: The current GC/MS assay was validated for
      linearity, intra-day and inter-day precisions, accuracy, extraction recovery and
      stability. The analyte calibration curves were linear over a wide concentration
      range and the lowest limit of quantifications (LLOQ) were 5.53 ng/mL (beta
      asarone), 6.50 ng/mL (alpha-asarone), 3.10 ng/mL (elemicin) and 7.60 ng/mL (cis
      methyl isoeugenol). After oral administration 0.9 g /Kg of AT rhizomes, the
      maximum plasma concentration (Cmax) was 2508.6+/-498.7 ng/mL for beta-asarone,
      257.5+/-37.1 ng/mL for alpha -asarone, 345.5+/-33.4 ng/mL for elemicin and
      452.7+/-59.1 ng/mL for cis-methyl isoeugenol, respectively. The time to reach the
      maximum plasma concentration (Tmax) was 1.42+/-0.18 h for beta-asarone, 1.58+/
      0.19 h for alpha -asarone, 1.67+/-0.24 h for elemicin and 1.75+/-0.38 h for cis
      methyl isoeugenol, respectively. CONCLUSION: This paper described a simple,
      sensitive and validated GC-MS method for simultaneous determination of four
      phenylpropanoids in rat plasma after oral administration of the essential oil of
      AT rhizomes and investigated on their pharmacokinetics studies as well.

PMID- 25046828
TI  - Plant species used in dental diseases: ethnopharmacology aspects and
      antimicrobial activity evaluation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological surveys show that several
      plant species are used empirically by the population, in oral diseases. However,
      it is necessary to check the properties of these plant species. AIM OF THE STUDY:
      To evaluate in vitro antimicrobial activity against Streptococcus mutans from
      plant species selected in a previous ethnopharmacology study. MATERIALS AND
      METHODS: An ethnopharmacological survey was conducted with users of a dental
      clinic school services, located in Sao Luis, Maranhao, Brazil, aiming to identify
      plant species used in oral diseases treatment. From the ethnopharmacological
      survey, species were selected for in vitro antimicrobial activity evaluation
      against Streptococcus mutans, by agar diffusion method and determination of
      Minimum Inhibitory Concentration (MIC). RESULTS: Two hundred and seventy one
      people participated in the research: 55.7% reported the use of plants for
      medicinal purposes, 29.5% of which have knowledge and/or use plants for some type
      of oral disease. Thirty four species belonging to 24 (twenty four) botanical
      families were reported, being Aloe vera L., Anacardium occidentale L., Schinus
      terebinthifolius Raddi, Chenopodium ambrosioides L. and Punica granatum L. the
      most cited. The most commonly reported indications were healing after tooth
      extraction, followed by toothache, inflammation and bleeding gums., The
      determination of Minimum Inhibitory Concentration (MIC) demonstrated that Punica
      granatum L., Psidium guajava L. and Schinus terebinthifolius Raddi showed similar
      activity to 0.12% chlorhexidine, used as positive control. CONCLUSION: That
      result is important to follow up the study of these species in the search for new
      anticariogenic agents originated by plants.

PMID- 25046829
TI  - Effects of a hemoglobin-based oxygen carrier (HBOC-201) and derivatives with
      altered oxygen affinity and viscosity on systemic and microcirculatory variables
      in a top-load rat model.
AB  - The effects of a polymerized bovine hemoglobin-based oxygen carrier (HBOC) and
      two derivatives on arteriolar vasoactivity and tissue oxygen tension were
      explored by administering HBOC in a dose-response fashion to normovolemic rats.
      The effect of oxygen affinity (P50) and viscosity was also explored, where the
      P50 and viscosity of the parent compound (HBOC-201) and its modifications (MP50
      and LP50A) were as follows: 40mmHg and 3.0cP (HBOC-20l); 18mmHg and 4.4cP (MP50);
      and 17mmHg and 12.1cP (LP50A). Anesthetized male Sprague-Dawley rats (N=32) were
      randomized to receive one of the HBOC solutions, and were administered four
      infusions that increased in concentration for each dose (2, 22, 230 and 780mg/kg,
      IV). Data were compared to rats receiving an equivalent volume for each of the
      four infusions (0.4, 0.4, 3.8, 13.1ml/kg, IV) of iso-oncotic 5.9% human serum
      albumin (HSA). Increasing doses of either HBOC solutions or HSA were associated
      with increasing MAP. Doses 3 and 4 of HBOC-201, MP50 and HSA produced significant
      increases in MAP, whereas similar increases began at a lower dose (Dose 2) with
      LP50A. There were no significant changes in arteriolar diameters at any dose for
      any group. Interstitial partial pressure of oxygen (ISF PO2) remained unchanged
      for HBOC-201, MP50 and HSA, but LP50A caused a significant decrease in ISF PO2
      compared to baseline after Doses 3 and 4. In conclusion, there was no evidence
      that HBOC-201 would perform better with increased oxygen affinity (40 to 18mmHg)
      or viscosity (3.0 to 4.4cP). 

PMID- 25046830
TI  - Imidazole-stabilized gold nanoparticles induce neuronal apoptosis: an in vitro
      and in vivo study.
AB  - Gold nanoparticles are increasingly being employed in innovative biological
      applications thanks to their advantages of material- and size-dependent physics
      and chemical interactions with the cellular systems. On the other hand, growing
      concern has emerged on the toxicity which would render gold-based nanoparticles
      harmful to cell cultures, animals, and humans. Emerging attention is focused on
      the interaction of gold nanoparticles with nervous system, especially regarding
      the ability to overcome the blood-brain barrier (BBB) which represents the major
      impediment to the delivery of therapeutics into the brain. We synthesized highly
      stable 2-mercapto-1-methylimidazole-stabilized gold-nanoparticles (AuNPs)-mmi to
      investigate their entry, accumulation, and toxicity in vitro (SH-SY5Y human
      neuroblastoma cells) and in vivo (brain of C57BL/6 mice) through optical and
      electron microscopy. After incubation in the cell culture medium at the lowest
      dose of 0.1 mg/mL the (AuNPs)-mmi nanoparticles were found compacted and
      recruited into endosome/lysosomes (1 h) before their fusion (2 h) and the onset
      of neuronal death by apoptosis (4 h) as proved by terminal-transferase-mediated
      dUTP nick end labeling assay and caspase-3 immunoreactivity. The ability of
      (AuNPs)-mmi to cross the BBB was assessed by injection in the caudal vein of
      C57BL/6 mice. Among different brain regions, the nanoparticles were found in the
      CaudatoPutamen area, mainly in the striatal neurons 4 h after injection. These
      neurons showed the typical hallmarks of apoptosis. Our findings provide, for the
      first time, the dynamic of 2-mercapto-1-methylimidazole nanogold uptake. The
      molecular mechanism which underlies the nanogold-driven apoptotic event is
      analyzed and discussed in order to take into account when designing nanomaterials
      to interface with biological structures.

PMID- 25046831
TI  - Identifying plausible adverse drug reactions using knowledge extracted from the
      literature.
AB  - Pharmacovigilance involves continually monitoring drug safety after drugs are put
      to market. To aid this process; algorithms for the identification of strongly
      correlated drug/adverse drug reaction (ADR) pairs from data sources such as
      adverse event reporting systems or Electronic Health Records have been developed.
      These methods are generally statistical in nature, and do not draw upon the large
      volumes of knowledge embedded in the biomedical literature. In this paper, we
      investigate the ability of scalable Literature Based Discovery (LBD) methods to
      identify side effects of pharmaceutical agents. The advantage of LBD methods is
      that they can provide evidence from the literature to support the plausibility of
      a drug/ADR association, thereby assisting human review to validate the signal,
      which is an essential component of pharmacovigilance. To do so, we draw upon vast
      repositories of knowledge that has been extracted from the biomedical literature
      by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD
      methods that scale comfortably to the volume of knowledge available in these
      repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model
      based on concept-level co-occurrence, and Predication-based Semantic Indexing
      (PSI), a model that encodes the nature of the relationship between concepts to
      support reasoning analogically about drug-effect relationships. An evaluation set
      was constructed from the Side Effect Resource 2 (SIDER2), which contains known
      drug/ADR relations, and models were evaluated for their ability to "rediscover"
      these relations. In this paper, we demonstrate that both RRI and PSI can recover
      known drug-adverse event associations. However, PSI performed better overall, and
      has the additional advantage of being able to recover the literature underlying
      the reasoning pathways it used to make its predictions. 

PMID- 25046832
TI  - Associating co-authorship patterns with publications in high-impact journals.
AB  - OBJECTIVES: To develop a method for investigating co-authorship patterns and
      author team characteristics associated with the publications in high-impact
      journals through the integration of public MEDLINE data and institutional
      scientific profile data. METHODS: For all current researchers at Columbia
      University Medical Center, we extracted their publications from MEDLINE authored
      between years 2007 and 2011 and associated journal impact factors, along with
      author academic ranks and departmental affiliations obtained from Columbia
      University Scientific Profiles (CUSP). Chi-square tests were performed on co
      authorship patterns, with Bonferroni correction for multiple comparisons, to
      identify team composition characteristics associated with publication impact
      factors. We also developed co-authorship networks for the 25 most prolific
      departments between years 2002 and 2011 and counted the internal and external
      authors, inter-connectivity, and centrality of each department. RESULTS: Papers
      with at least one author from a basic science department are significantly more
      likely to appear in high-impact journals than papers authored by those from
      clinical departments alone. Inclusion of at least one professor on the author
      list is strongly associated with publication in high-impact journals, as is
      inclusion of at least one research scientist. Departmental and disciplinary
      differences in the ratios of within- to outside-department collaboration and
      overall network cohesion are also observed. CONCLUSIONS: Enrichment of co
      authorship patterns with author scientific profiles helps uncover associations
      between author team characteristics and appearance in high-impact journals. These
      results may offer implications for mentoring junior biomedical researchers to
      publish on high-impact journals, as well as for evaluating academic progress
      across disciplines in modern academic medical centers.

PMID- 25046834
TI  - Double umbilical cord blood transplantation after novel myeloablative
      conditioning using a regimen of fludarabine, busulfan, and total lymphoid
      irradiation.
AB  - We conducted a pilot study evaluating double umbilical cord blood transplantation
      (dCBT) after myeloablative conditioning with fludarabine and busulfan 3.2 mg/kg
      i.v. * 4, followed by total lymphoid irradiation at 400 cGy (FluBu4/TLI) for any
      indicated hematological disorder for patients without a suitable donor. Twenty
      patients with predominantly high-risk disease underwent dCBT according to
      protocol. The regimen was well tolerated, with mucositis as the primary observed
      toxicity (n = 19). The cumulative incidence of neutrophil engraftment was 89%
      (95% confidence interval [CI], 64% to 97%), with a median time to recovery of 16
      days (range, 12 to 31 days). All evaluable patients with neutrophil engraftment
      achieved complete donor chimerism by day 40. The cumulative incidence of grades
      III and IV acute graft-versus-host disease (GVHD) at day 100 was 10% (95% CI, 2%
      to 27%), and the cumulative incidence of chronic GVHD was 35% (95% CI, 16% to
      55%) by the end of the study. At 1 year, the cumulative incidence of treatment
      related mortality (TRM) was 35% (95% CI, 16% to 55%). The leading cause of
      nonrelapse mortality was acute GVHD (n = 4), followed by graft failure (n = 2)
      and chronic GVHD (n = 1). TRM was significantly associated with a
      pretransplantation hematopoietic cell transplantation-specific comorbidity index
      score >= 3 (P = .005). At 1 year, disease relapse occurred in 6 patients and
      overall survival was 40% (95% CI, 19% to 60%). We conclude that FluBu4/TLI is an
      adequate preparative regiment before dCBT, providing high engraftment rates and
      relatively early neutrophil recovery. The best survival outcomes were seen in
      patients without significant comorbidities before transplantation, and outcomes
      are comparable to previously published dCBT studies. 

PMID- 25046835
TI  - Imaging genetics in obsessive-compulsive disorder: linking genetic variations to
      alterations in neuroimaging.
AB  - Obsessive-compulsive disorder (OCD) occurs in ~1-3% of the general population,
      and its often rather early onset causes major disabilities in the everyday lives
      of patients. Although the heritability of OCD is between 35 and 65%, many
      linkage, association, and genome-wide association studies have failed to identify
      single genes that exhibit high effect sizes. Several neuroimaging studies have
      revealed structural and functional alterations mainly in cortico-striato-thalamic
      loops. However, there is also marked heterogeneity across studies. These
      inconsistencies in genetic and neuroimaging studies may be due to the
      heterogeneous and complex phenotypes of OCD. Under the consideration that genetic
      variants may also influence neuroimaging in OCD, researchers have started to
      combine both domains in the field of imaging genetics. Here, we conducted a
      systematic search of PubMed and Google Scholar literature for articles that
      address genetic imaging in OCD and related disorders (published through March
      2014). We selected 8 publications that describe the combination of imaging
      genetics with OCD, and extended it with 43 publications of comorbid psychiatric
      disorders. The most promising findings of this systematic review point to the
      involvement of variants in genes involved in the serotonergic (5-HTTLPR, HTR2A),
      dopaminergic (COMT, DAT), and glutamatergic (SLC1A1, SAPAP) systems. However, the
      field of imaging genetics must be further explored, best through investigations
      that combine multimodal imaging techniques with genetic profiling, particularly
      profiling techniques that employ polygenetic approaches, with much larger sample
      sizes than have been used up to now. 

PMID- 25046833
TI  - Older patients with myeloma derive similar benefit from autologous
      transplantation.
AB  - Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is
      performed less often in people >70 years old than in people <=70 years old. We
      analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to
      the Center for International Blood and Marrow Transplant Research between 2008
      and 2011, representing the majority of US AHCT activity during this period.
      Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69
      years (n = 4666), and >70 years (n = 946). Median OS was not reached for any
      cohort. In multivariate analysis, increasing age was associated with mortality (P
      = .0006). Myeloma-specific mortality was similar among cohorts at 12%, indicating
      an age-related effect on nonmyeloma mortality. Analyses were performed in a
      representative subgroup comparing relapse rate, progression-free survival (PFS),
      and nonrelapse mortality (NRM). One-year NRM was 0% for age >70 years and 2% for
      other ages (P = not significant). The three-year relapse rate was 56% in age 18
      to 59 years, 61% in age 60 to 69 years, and 63% age >70 (P = not significant).
      Three-year PFS was similar at 42% in age 18 to 59 years, 38% in age 60 to 69
      years, and 33% in age >70 years (P = not significant). Postrelapse survival was
      significantly worse for the older cohort (P = .03). Older subjects selected for
      AHCT derived similar antimyeloma benefit without worse NRM, relapse rate, or PFS.

PMID- 25046836
TI  - Proteomic analysis of the mitochondria from embryonic and postnatal rat brains
      reveals response to developmental changes in energy demands.
AB  - Many biological processes converge on the mitochondria. In such systems, where
      many pathways converge, manipulation of the components can produce varied and far
      reaching effects. Due to the centrality of the mitochondria in many cellular
      pathways, we decided to investigate the brain mitochondrial proteome during early
      development. Using a SWATH mass spectrometry-based technique, we were able to
      identify vast proteomic alterations between whole brain mitochondria from rats at
      embryonic day 18 compared to postnatal day 7. These findings include
      statistically significant alterations in proteins involved in glycolysis and
      mitochondrial trafficking/dynamics. Additionally, bioinformatic analysis enabled
      the identification of HIF1A and XBP1 as upstream transcriptional regulators of
      many of the differentially expressed proteins. These data suggest that the cell
      is rearranging the mitochondria to accommodate special energy demands and that
      cytosolic proteins exert mitochondrial effects through dynamic interactions with
      the mitochondria. BIOLOGICAL SIGNIFICANCE: Although mitochondria play critical
      roles in many cellular pathways, our understanding of how these organelles change
      over time is limited. The changes occurring in the mitochondria at early time
      points are especially important as many mitochondrial disorders produce
      neurological dysfunction early in life. Herein, we utilize a SWATH mass
      spectrometry approach to quantify proteomic alterations of rat brain mitochondria
      between embryonic and postnatal stages. We found this method to be highly
      reproducible, enabling the identification of alterations in many biochemical
      pathways and mitochondrial properties. This insight into the distinct changes in
      these biological pathways to maintain homeostasis under divergent conditions will
      help elucidate the pathological changes occurring in disease states.

PMID- 25046838
TI  - Antispasmodic and myorelaxant effects of the flavoring agent methyl cinnamate in
      gut: potential inhibition of tyrosine kinase.
AB  - Methyl cinnamate (MC) is a safe flavoring agent useful to food industry. Although
      chemically analog to tyrosine kinase inhibitors, there is little information
      regarding its biological actions. Here, we aimed at assessing the MC effects on
      gastrointestinal contractility and the putative involvement of tyrosine kinase in
      the mediation of these effects. Isometric contractions were recorded in rat
      isolated strips from stomach, duodenum and colon segments. In gastric strips, MC
      (3-3000 uM) showed antispasmodic effects against carbachol-induced contractions,
      which remained unchanged by either l-NAME or tetraethylammonium pretreatment and
      occurred with potency similar to that obtained against contractions evoked by
      potassium or U-46619. In colon strips, MC was four times more potent than in
      gastric ones. MC and the positive control genistein inhibited phasic contractions
      induced by acetylcholine in Ca2+-free medium, an effect fully prevented by sodium
      orthovanadate. Both MC and genistein decreased the spontaneous contractions of
      duodenal strips and shortened the time necessary for gastric fundic tissues to
      reach 50% of maximal relaxation. In freshly isolated colon myocytes, MC decreased
      the basal levels of cytoplasmic Ca2+, but not the potassium-elicited cytoplasmic
      Ca2+ elevation. Colon strips obtained from rats subjected to intracolonic acetic
      acid instillation showed reduced contractility to potassium, which was partially
      recovered in MC-treated rats. Inhibitory effect of nifedipine against cholinergic
      contractions, blunted in acetic acid-induced colitis, was also recovered in MC
      treated rats. In conclusion, MC inhibited the gastrointestinal contractility with
      a probable involvement of tyrosine kinase pathways. In vivo, it was effective to
      prevent the deleterious effects of colitis resulting from acetic acid injury.

PMID- 25046839
TI  - 3-O-[N-(p-fluorobenzenesulfonyl)-carbamoyl]-oleanolic acid, a semisynthetic
      analog of oleanolic acid, induces apoptosis in breast cancer cells.
AB  - Oleanolic acid (OA), a pentacyclic triterpene acid widely distributed in food and
      traditional herbal remedies, exhibits diverse therapeutic effects. OA has been
      subjected to various chemical modifications to optimize its anticancer effect.
      Among other analogs, 3-O-[N-(p-fluorobenzenesulfonyl)-carbamoyl]-oleanolic acid
      (PFOA) was semisynthesized from OA. This study evaluates the cytotoxic effects of
      PFOA on MDA-MB-231, MCF-7, BT-474, and T-47D human breast cancer cells. Acute
      treatment of PFOA inhibited breast cancer cell viability in a dose-dependent
      manner. Treatment of PFOA at cytotoxic doses significantly induced apoptosis in
      cancer cells as shown by flow cytometry analysis. Activation of apoptosis in MCF
      7 and BT-474 cells seemed to be initiated through induction of Fas ligand, which
      resulted in activation of caspase-8 and PARP-1, whereas apoptosis in MDA-MB-231
      cells was initiated by the activation of caspase-9, caspase-3 and PARP-1. The
      mechanism of apoptosis induction in T-47D involves activation of PARP-1. PFOA
      decreased the expression of EGFR, HER-2, MET and ERalpha in human breast cancer
      cell lines. These findings suggest that PFOA inhibits cell growth, activates
      apoptosis, and decreases the expression of key proteins involved in progression
      of breast cancer. 

PMID- 25046840
TI  - Neuropeptide FF receptors exhibit direct and anti-opioid effects on mice dorsal
      raphe nucleus neurons.
AB  - By using acutely dissociated dorsal raphe nucleus neurons (DRN) from young mice,
      direct and anti-opioid effects of Neuropeptide FF (NPFF) receptors were measured.
      The NPFF analog 1 DMe (10 uM) had no effect on resting Ca2+ channels but reduced
      the magnitude of Ca2+ transients induced by depolarization in 83.3% neurons
      tested, of which the inhibition rate is 45.4+/-2.9%. Pertussis toxin treatment
      reduced to 18.9% the number of responding neurons and attenuated by 47% the
      response of 1 DMe. In contrast, cholera toxin treatment had no significant
      effect. Eighteen minute perfusion with 1 DMe at a very low 10 nM concentration,
      that did not directly inhibit Ca2+ transients triggered by depolarization in
      every neuron, attenuated by 78% the inhibitory effect of Nociceptin/orphanin FQ
      (N/OFQ) on Ca2+ transients, but not that of by serotonin. These results
      demonstrated for the first time that NPFF receptors on mice DRN inhibit Ca2+
      transients induced by depolarization via Gi/o protein and also exhibit a specific
      anti-opioid activity on nociceptin receptors, and that their specific anti-opioid
      activity is not a direct consequence of their activity on Ca2+ transients.

PMID- 25046841
TI  - Effects of menthol on circular smooth muscle of human colon: analysis of the
      mechanism of action.
AB  - Menthol is the major constituent of peppermint oil, an herbal preparation
      commonly used to treat nausea, spasms during colonoscopy and irritable bowel
      disease. The mechanism responsible for its spasmolytic action remains unclear.
      The aims of this study were to investigate the effects induced by menthol on the
      human distal colon mechanical activity in vitro and to analyze the mechanism of
      action. The spontaneous or evoked-contractions of the circular smooth muscle were
      recorded using vertical organ bath. Menthol (0.1 mM-30 mM) reduced, in a
      concentration-dependent manner, the amplitude of the spontaneous contractions
      without affecting the frequency and the resting basal tone. The inhibitory effect
      was not affected by 5-benzyloxytryptamine (1 MUM), a transient receptor potential
      melastatin8 channel antagonist, or tetrodotoxin (1 MUM), a neural blocker, or 1H
      [1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (10 uM), inhibitor of nitric oxide
      (NO)-sensitive soluble guanylyl cyclase, or tetraethylammonium (10 mM), a blocker
      of potassium (K+)-channels. On the contrary, nifedipine (3 nM), a voltage
      activated L-type Ca2+ channel blocker, significantly reduced the inhibitory
      menthol actions. Menthol also reduced in a concentration-dependent manner the
      contractile responses caused by exogenous application of Ca2+ (75-375 MUM) in a
      Ca2+-free solution, or induced by potassium chloride (KCl; 40 mM). Moreover
      menthol (1-3 mM) strongly reduced the electrical field stimulation (EFS)-evoked
      atropine-sensitive contractions and the carbachol-contractile responses. The
      present results suggest that menthol induces spasmolytic effects in human colon
      circular muscle inhibiting directly the gastrointestinal smooth muscle
      contractility, through the block of Ca2+ influx through sarcolemma L-type Ca2+
      channels.

PMID- 25046842
TI  - Cancer and bone: a complex complex.
AB  - Primary and secondary bone cancers are rare events. However, once settled, a
      complex process is started involving an extensive amount of factors and
      interactions. The bone micro-environment is a preferential site for (metastatic)
      tumor cells to enter, stay, colonize and expand. The fact that the tumor cells
      affect the complete bone environment involving many cell types and regulatory
      pathways to stimulate their own growth and escape from therapy is devastating for
      the patient. Many efforts have been made to get more insight into the mechanisms
      underlying the communication between bone cells and cancer cells and progress is
      made in therapeutic interventions. This review will discuss the biological
      mechanisms of primary bone malignancies (osteosarcoma, Ewing's sarcoma,
      chondrosarcoma, multiple myeloma) and secondary bone malignancies (bone
      metastases) and therapeutic interventions. 

PMID- 25046844
TI  - Effect of remote ischemic postconditioning on patients undergoing living donor
      liver transplantation.
AB  - The aim of this study was to evaluate the protective effect of remote ischemic
      postconditioning (RIPostC) on graft function and acute kidney injury (AKI) after
      living donor liver transplantation (LT). Recipients undergoing elective living
      donor LT were randomly assigned to either the RIPostC group or the control group.
      Immediately after reperfusion, 4 cycles of ischemia and reperfusion lasting for 5
      minutes each were performed on 1 upper limb in the RIPostC group. Graft function
      was assessed through evaluations of the serum levels of total bilirubin and liver
      enzymes and the prothrombin time for 28 days after surgery. The incidence of AKI,
      as defined by the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease
      classification, was evaluated within 28 days of the operation. In addition, the
      incidences of graft dysfunction, acute cellular rejection, and major
      complications; the 1-, 3-, and 6-month mortality rates; the length of stay in the
      intensive care unit; and the length of hospital stay were also investigated. In
      all, 78 patients were enrolled in the analysis (n = 39 in each group). No
      differences in graft function or clinical outcomes were observed between the
      groups. The incidences of postoperative AKI were 38% (n = 15) in the RIPostC
      group and 72% (n = 28) in the control group (P = 0.006). Despite no improvements
      in postoperative graft function, RIPostC decreased the incidence of postoperative
      AKI after living donor LT in this study. However, no other clinical benefits with
      respect to the complication rate, length of hospital stay, or short-term
      mortality rate were observed. Thus, further studies will be needed to evaluate
      the clinical efficacy of RIPostC in LT fully.

PMID- 25046843
TI  - Deformable registration for quantifying longitudinal tumor changes during
      neoadjuvant chemotherapy.
AB  - PURPOSE: To evaluate DRAMMS, an attribute-based deformable registration
      algorithm, compared to other intensity-based algorithms, for longitudinal breast
      MRI registration, and to show its applicability in quantifying tumor changes over
      the course of neoadjuvant chemotherapy. METHODS: Breast magnetic resonance images
      from 14 women undergoing neoadjuvant chemotherapy were analyzed. The accuracy of
      DRAMMS versus five intensity-based deformable registration methods was evaluated
      based on 2,380 landmarks independently annotated by two experts, for the entire
      image volume, different image subregions, and patient subgroups. The registration
      method with the smallest landmark error was used to quantify tumor changes, by
      calculating the Jacobian determinant maps of the registration deformation.
      RESULTS: DRAMMS had the smallest landmark errors (6.05 +/- 4.86 mm), followed by
      the intensity-based methods CC-FFD (8.07 +/- 3.86 mm), NMI-FFD (8.21 +/- 3.81
      mm), SSD-FFD (9.46 +/- 4.55 mm), Demons (10.76 +/- 6.01 mm), and Diffeomorphic
      Demons (10.82 +/- 6.11 mm). Results show that registration accuracy also depends
      on tumor versus normal tissue regions and different patient subgroups.
      CONCLUSIONS: The DRAMMS deformable registration method, driven by attribute
      matching and mutual-saliency, can register longitudinal breast magnetic resonance
      images with a higher accuracy than several intensity-matching methods included in
      this article. As such, it could be valuable for more accurately quantifying
      heterogeneous tumor changes as a marker of response to treatment.

PMID- 25046845
TI  - T2* relaxometry of fetal brain at 1.5 Tesla using a motion tolerant method.
AB  - PURPOSE: The aim of this study was to determine T2* values for the fetal brain in
      utero and to compare them with previously reported values in preterm and term
      neonates. Knowledge of T2* may be useful for assessing brain development, brain
      abnormalities, and for optimizing functional imaging studies. METHODS: Maternal
      respiration and unpredictable fetal motion mean that conventional multishot
      acquisition techniques used in adult T2* relaxometry studies are not practical.
      Single shot multiecho echo planar imaging was used as a rapid method for
      measuring fetal T2* by effectively freezing intra-slice motion. RESULTS: T2*
      determined from a sample of 24 subjects correlated negatively with gestational
      age with mean values of 220 ms (+/-45) for frontal white matter, 159 ms (+/-32)
      for thalamic gray matter, and 236 ms (+/-45) for occipital white matter.
      CONCLUSION: Fetal T2* values are higher than those previously reported for
      preterm neonates and decline with a consistent trend across gestational age. The
      data suggest that longer than usual echo times or direct T2* measurement should
      be considered when performing fetal fMRI to reach optimal BOLD sensitivity.

PMID- 25046846
TI  - Effect of ethanol, dry extract and reducing sugars on density and viscosity of
      Brazilian red wines.
AB  - BACKGROUND: Density and viscosity are properties that exert great influence on
      the body of wines. The present work aimed to evaluate the influence of the
      alcoholic content, dry extract, and reducing sugar content on density and
      viscosity of commercial dry red wines at different temperatures. The rheological
      assays were carried out on a controlled stress rheometer, using concentric
      cylinder geometry at seven temperatures (2, 8, 14, 16, 18, 20 and 26  degrees C).
      RESULTS: Wine viscosity decreased with increasing temperature and density was
      directly related to the wine alcohol content, whereas viscosity was closely
      linked to the dry extract. Reducing sugars did not influence viscosity or
      density. Wines produced from Italian grapes were presented as full-bodied with
      higher values for density and viscosity, which was linked to the higher alcohol
      content and dry extract, respectively. CONCLUSION: The results highlighted the
      major effects of certain physicochemical properties on the physical properties of
      wines, which in turn is important for guiding sensory assessments.

PMID- 25046847
TI  - Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive
      chronic hepatitis B treated with tenofovir disoproxil fumarate.
AB  - BACKGROUND & AIMS: In a study of 266 chronic hepatitis B e antigen (HBeAg)
      positive patients, 23 experienced hepatitis B surface antigen (HBsAg) loss with
      up to 5 years of tenofovir disoproxil fumarate (TDF) treatment. HBsAg kinetics in
      patients with and without HBsAg loss and predictors of HBsAg loss were evaluated.
      METHODS: HBsAg levels were quantified every 12 weeks. A multivariable regression
      analysis, involving prespecified baseline characteristics and on-treatment
      response parameters, was performed; a stepwise procedure identified independent
      predictors of HBsAg loss. RESULTS: Among patients with HBsAg loss, 14 (61%), 1
      (4%), 0 and 7 (30%) were genotypes A through D, respectively; 1 (4%) was genotype
      F. HBsAg loss was preceded by viral suppression (HBV DNA <29 IU/ml; n=23) and
      HBeAg loss (n=19). Among treated patients the strongest independent predictors of
      HBsAg loss were Caucasian race with genotype A/D and ?4 years of infection
      (HR=14.3, 95% confidence interval [CI] 4.7-43.4; p<0.0001) and an HBsAg decline
      of ?1 log10 IU/ml at week 24 (HR=13.7, 95% CI 5.6-33.7; p<0.0001). Among TDF
      treated patients, a reduction in HBsAg level of ?1-log10 by week 12 or 24 had a
      positive predictive value of 35%-45%, respectively, and a negative predictive
      value of 94%-97%, respectively. CONCLUSIONS: HBsAg loss in HBeAg-positive
      patients receiving TDF involves a chronology of virologic and serologic
      responses; patients with HBV genotypes A or D and a rapid early decline in HBsAg
      are more likely to lose HBsAg.

PMID- 25046849
TI  - mTOR-inhibitors may aggravate chronic hepatitis E.

PMID- 25046848
TI  - Gli1 activation and protection against hepatic encephalopathy is suppressed by
      circulating transforming growth factor beta1 in mice.
AB  - BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a neurologic disorder that
      develops during liver failure. Few studies exist investigating systemic-central
      signalling during HE outside of inflammatory signalling. The transcription factor
      Gli1, which can be modulated by hedgehog signalling or transforming growth factor
      beta1 (TGFbeta1) signalling, has been shown to be protective in various
      neuropathies. We measured Gli1 expression in brain tissues from mice and
      evaluated how circulating TGFbeta1 and canonical hedgehog signalling regulate its
      activation. METHODS: Mice were injected with azoxymethane (AOM) to induce liver
      failure and HE in the presence of Gli1 vivo-morpholinos, the hedgehog inhibitor
      cyclopamine, Smoothened vivo-morpholinos, a Smoothened agonist, or TGFbeta
      neutralizing antibodies. Molecular analyses were used to assess Gli1, hedgehog
      signalling, and TGFbeta1 signalling in the liver and brain of AOM mice and HE
      patients. RESULTS: Gli1 expression was increased in brains of AOM mice and in HE
      patients. Intra-cortical infusion of Gli1 vivo-morpholinos exacerbated the
      neurologic deficits of AOM mice. Measures to modulate hedgehog signalling had no
      effect on HE neurological decline. Levels of TGFbeta1 increased in the liver and
      serum of mice following AOM administration. TGFbeta neutralizing antibodies
      slowed neurologic decline following AOM administration without significantly
      affecting liver damage. TGFbeta1 inhibited Gli1 expression via a SMAD3-dependent
      mechanism. Conversely, inhibiting TGFbeta1 increased Gli1 expression.
      CONCLUSIONS: Cortical activation of Gli1 protects mice from induction of HE.
      TGFbeta1 suppresses Gli1 in neurons via SMAD3 and promotes the neurologic
      decline. Strategies to activate Gli1 or inhibit TGFbeta1 signalling might be
      developed to treat patients with HE.

PMID- 25046851
TI  - Effects of persistent organochlorine exposure on the liver transcriptome of the
      common minke whale (Balaenoptera acutorostrata) from the North Pacific.
AB  - Hepatic concentrations of persistent organochlorines (OCs) were determined in the
      common minke whale (Balaenoptera acutorostrata) from the North Pacific. To
      investigate the effects of OCs on the transcriptome in the minke whale, the
      present study constructed a hepatic oligo array of this species where 985 unique
      oligonucleotides were spotted and further analyzed the relationship between the
      OC levels and gene expression profiles of liver tissues. The stepwise multiple
      linear regression analysis identified 32 genes that correlated with hepatic OC
      levels. The mRNA expression levels of seven cytochrome P450 (CYP) genes, CYP1A1,
      1A2, 2C78, 2E1, 3A72, 4A35, and 4V6 showed no clear correlations with the
      concentration of each OC, suggesting that the accumulated OCs in the liver did
      not reach levels that could alter CYP expression. Among the genes screened by the
      custom oligo array analysis, hepatic mRNA expression levels of 16 genes were
      further measured using quantitative real-time reverse transcription polymerase
      chain reaction. The mRNA levels of vitamin D-binding protein (DBP) were
      negatively correlated with non-ortho coplanar polychlorinated biphenyl (PCB)
      levels. Androgen receptor-associated coregulator 70 (ARA70) expression levels
      showed a significant positive correlation with concentrations of non-ortho
      coplanar PCB169. These correlations suggest that coplanar PCB-reduced DBP
      expression could suppress vitamin D receptor-mediated signaling cascades in
      peripheral tissues. Alternatively, the suppression of vitamin D receptor
      signaling cascade could be enhanced through competition with the androgen
      receptor signaling pathway for ARA70. In addition, a negative correlation between
      kynureninase and PCB169 levels was also observed, which suggest an enhanced
      accumulation of an endogenous aryl hydrocarbon receptor agonist, kynurenine in
      the minke whale population. Further studies are necessary to translate the
      changes in the transcriptome to toxicological outcomes including the disruption
      of the nervous and immune systems. 

PMID- 25046852
TI  - Inhalation and dermal exposure to atmospheric polycyclic aromatic hydrocarbons
      and associated carcinogenic risks in a relatively small city.
AB  - The aim of this study was to conduct a carcinogenic risk assessment for exposure
      to polycyclic aromatic hydrocarbons (PAHs) via routes of inhalation and dermal
      contact. Concentrations of 19 PAH species were determined during a heating period
      at a site in the city of Balikesir, Turkey. Two questionnaires were administered
      to a sample of inhabitants to determine time-activity budgets and demographic
      information. The assessment was conducted for each participant and Balikesir
      population by deterministic and probabilistic approaches, respectively. Monte
      Carlo simulation was implemented to determine the population exposure-risk
      probability distributions. The estimates were based on benzo[a]pyrene equivalent
      (BaPeq) total PAH concentrations calculated using toxic equivalency factors. The
      mean and median BaPeq concentrations of gaseous and particulate phases were 3.25
      and 1.34, and 38.5 and 34.0ng/m(3), respectively. Carcinogenic risk for
      inhalation exposure route was estimated by using two different slope factor
      values (3.9 and 304.5(mg/kg-day)(-1)), recommended by two different
      organizations, resulting in two (order(s) of magnitude apart) population risk
      ranges: 1.32*10(-7)-2.23*10(-4), and 1.61*10(-5)-7.95*10(-3), respectively. The
      population risks associated with dermal exposure were lower compared to those of
      inhalation, ranging from 6.58*10(-9) to 2.57*10(-6). The proportion of the
      population with risks higher than the general acceptable level (1.0*10(-6)) was
      estimated as >99 percent, for inhalation, and as 28 percent for dermal exposure
      route. 

PMID- 25046850
TI  - Using ecological momentary assessment to examine interpersonal and affective
      predictors of loss of control eating in adolescent girls.
AB  - OBJECTIVE: Pediatric loss of control (LOC) eating is predictive of partial- and
      full-syndrome binge eating disorder. The interpersonal model proposes that LOC
      eating is used to cope with negative mood states resulting from interpersonal
      distress, possibly on a momentary level. We therefore examined temporal
      associations between interpersonal problems, negative affect, and LOC eating
      among overweight adolescent girls using ecological momentary assessment (EMA).
      METHOD: Thirty overweight and obese (>=85th body mass index (BMI) percentile;
      BMI: M = 36.13, SD = 7.49 kg/m(2)) adolescent females (Age: M = 14.92, SD = 1.54
      y; 60.0% African American) who reported at least two LOC episodes in the past
      month completed self-report momentary ratings of interpersonal problems, state
      affect, and LOC eating for 2 weeks. A series of 2-level multilevel models with
      centering within subjects was conducted. RESULTS: Between- and within-subjects
      interpersonal problems (p's < .05), but not between- (p = .12) or within- (p =
      .32) subjects negative affect predicted momentary LOC eating. At the between
      subjects level, interpersonal problems significantly predicted increases in
      negative affect (p < 001). DISCUSSION: Naturalistic data lend support to the
      predictive value of interpersonal problems for LOC eating among adolescents.
      Interventions targeting interpersonal factors on a momentary basis may be useful
      during this developmental stage.

PMID- 25046853
TI  - Protective roles of nitric oxide on seed germination and seedling growth of rice
      (Oryza sativa L.) under cadmium stress.
AB  - Nitric oxide (NO) is a bioactive molecule in plants which mediates a variety of
      physiological processes and responses to biotic and abiotic stresses including
      heavy metals. In the present study, the effects of exogenous NO donor sodium
      nitroprusside (SNP) on rice seed germination and seedlings growth were
      investigated under Cd stress and a possible mechanism was postulated. The results
      indicated that 100MUM Cd significantly decreased rice seed germination index,
      vigor index, root and shoot lengths as well as fresh weight compared to control.
      Exogenous SNP dose-dependently attenuated the inhibition of rice seed germination
      and thereafter seedling growth caused by Cd. The promoting effect was most
      pronounced at 30MUM SNP. Cd exposure caused oxidative stress by elevating
      hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents in root and shoot of
      rice seedlings. 30MUM SNP counteracted partly Cd toxicity by reducing the H2O2
      and MDA contents of Cd-exposed seedlings. Meanwhile, application of SNP markedly
      stimulated the activities of superoxide dismutases (SOD), ascorbate peroxidases
      (APX), guaiacol peroxidase (POD) and catalases (CAT) compared with Cd treatment
      alone, thereby indicating the enhancement of the antioxidative capacity in the
      root and shoot under Cd stress. In addition, addition of 30MUM SNP increased
      accumulation of proline in both root and shoot. The Cd accumulation in seedlings
      was significant reduced by SNP, implicating that the protective role of SNP was
      responsible for preventing Cd accumulation. However, the effects of SNP were
      reverted by addition of cPTIO, a NO scavenger, suggesting the protective roles of
      SNP might be related to the induction of NO. Furthermore, K3Fe(CN)6 and [Formula:
      see text] / [Formula: see text] had no similar roles as SNP. Based on these
      results, it can be concluded that SNP exerted an advantageous effect on
      alleviating the inhibitory effect of Cd on rice seed germination and seedling
      growth, which might interact with NO. 

PMID- 25046854
TI  - Th17-biased RORgammat transgenic mice become susceptible to a viral model for
      multiple sclerosis.
AB  - In a viral model for multiple sclerosis (MS), Theiler's murine encephalomyelitis
      virus-induced demyelinating disease (TMEV-IDD), both immune-mediated tissue
      damage (immunopathology) and virus persistence have been shown to cause
      pathology. T helper (Th) 17 cells are a Th cell subset, whose differentiation
      requires the transcription factor retinoic acid-related orphan receptor (ROR)
      gammat, secrete pro-inflammatory cytokines, including IL-17, and can antagonize
      Th1 cells. Although Th17 cells have been shown to play a pathogenic role in
      immune-mediated diseases or a protective role in bacterial and fungal infections,
      their role in viral infections is unclear. Using newly established Th17-biased
      RORgammat Tg mice, we tested whether Th17 cells could play a pathogenic or
      protective role in TMEV-IDD by contributing to immunopathology and/or by
      modulating anti-viral Th1 immune responses. While TMEV-infected wild-type
      littermate C57BL/6 mice are resistant to TMEV-IDD, RORgammat Tg mice developed
      inflammatory demyelinating lesions with virus persistence in the spinal cord.
      TMEV-infected RORgammat Tg mice had higher levels of IL-17, lower levels of
      interferon-gamma, and fewer CD8(+) T cells, without alteration in overall levels
      of anti-viral lymphoproliferative and antibody responses, compared with TMEV
      infected wild-type mice. This suggests that a Th17-biased "gain-of-function"
      mutation could increase susceptibility to virus-mediated demyelinating diseases. 

PMID- 25046856
TI  - Graft of the gelatin sponge scaffold containing genetically-modified neural stem
      cells promotes cell differentiation, axon regeneration, and functional recovery
      in rat with spinal cord transection.
AB  - Biological materials combined with genetically-modified neural stem cells (NSCs)
      are candidate therapy targeting spinal cord injury (SCI). Based on our previous
      studies, here we performed gelatin sponge (GS) scaffold seeded with neurotrophin
      3 (NT-3) and its receptor TrkC gene modifying NSCs for repairing SCI. Eight weeks
      later, compared with other groups, neurofilament-200 and 5-hydroxytryptamine
      positive nerve fibers were more in the injury site of the N+T-NSCs group.
      Immunofluorescence staining showed the grafted NSCs could differentiate into
      microtubule associated protein (Map2), postsynaptic density (PSD95), and mouse
      oligodendrocyte special protein (MOSP) positive cells. The percentage of the
      Map2, PSD95, and MOSP positive cells in the N+T-NSCs group was higher than the
      other groups. Immuno-electron microscopy showed the grafted NSCs making contact
      with each other in the injury site. Behavioral analysis indicated the recovery of
      hindlimbs locomotion was better in the groups receiving cell transplant, the best
      recovery was found in the N+T-NSCs group. Electrophysiology revealed the
      amplitude of cortical motor evoked potentials was increased significantly in the
      N+T-NSCs group, but the latency remained long. These findings suggest the GS
      scaffold containing genetically-modified NSCs may bridge the injury site, promote
      axon regeneration and partial functional recovery in SCI rats.

PMID- 25046855
TI  - Dynamic multiprotein assemblies shape the spatial structure of cell signaling.
AB  - Cell signaling underlies critical cellular decisions. Coordination, efficiency as
      well as fail-safe mechanisms are key elements. How the cell ensures that these
      hallmarks are at play are important questions. Cell signaling is often viewed as
      taking place through discrete and cross-talking pathways; oftentimes these are
      modularized to emphasize distinct functions. While simple, convenient and clear,
      such models largely neglect the spatial structure of cell signaling; they also
      convey inter-modular (or inter-protein) spatial separation that may not exist.
      Here our thesis is that cell signaling is shaped by a network of multiprotein
      assemblies. While pre-organized, the assemblies and network are loose and
      dynamic. They contain transiently-associated multiprotein complexes which are
      often mediated by scaffolding proteins. They are also typically anchored in the
      membrane, and their continuum may span the cell. IQGAP1 scaffolding protein which
      binds proteins including Raf, calmodulin, Mek, Erk, actin, and tens more, with
      actin shaping B-cell (and likely other) membrane-anchored nanoclusters and
      allosterically polymerizing in dynamic cytoskeleton formation, and Raf anchoring
      in the membrane along with Ras, provides a striking example. The multivalent
      network of dynamic proteins and lipids, with specific interactions forming and
      breaking, can be viewed as endowing gel-like properties. Collectively, this
      reasons that efficient, productive and reliable cell signaling takes place
      primarily through transient, preorganized and cooperative protein-protein
      interactions spanning the cell rather than stochastic, diffusion-controlled
      processes. 

PMID- 25046857
TI  - Cellular mechanism of premature ventricular contraction-induced cardiomyopathy.
AB  - BACKGROUND: Frequent premature ventricular contractions (PVCs) are associated
      with increased risk of sudden cardiac death and can cause secondary
      cardiomyopathy. OBJECTIVE: We sought to determine the mechanism(s) responsible
      for prolonged refractory period and left ventricular (LV) dysfunction
      demonstrated in our canine model of PVC-induced cardiomyopathy. METHODS: Single
      myocytes were isolated from LV free wall of PVC and control canines and used for
      patch-clamp recording, intracellular Ca(2+) measurements, and
      immunocytochemistry/confocal microscopy. LV tissues adjacent to the area of
      myocyte isolation were used for the immunoblot quantification of protein
      expression. RESULTS: In the PVC group, LV ejection fraction decreased from 57.6%
      +/- 1.5% to 30.4% +/- 3.1% after >=4 months of ventricular bigeminy. Compared to
      control myocytes, PVC myocytes had decreased densities of both outward (transient
      outward current [Ito] and inward rectifier current [IK1]) and inward (L-type Ca
      current [ICaL]) currents, but no consistent changes in rapid or slow delayed
      rectifier currents. The reduction in Ito, IK1, and ICaL was accompanied by
      decreased protein levels of their channel subunits. The extent of reduction in
      Ito, IK1, and ICaL varied among PVC myocytes, creating marked heterogeneity in
      action potential configurations and durations. PVC myocytes showed impaired Ca
      induced Ca release from the sarcoplasmic reticulum (SR), without increase in SR
      Ca leak or decrease in SR Ca store. This was accompanied by a decrease in dyad
      scaffolding protein, junctophilin-2, and loss of Cav1.2 registry with Ca
      releasing channels (ryanodine receptor 2). CONCLUSION: PVCs increase dispersion
      of action potential configuration/duration, a risk factor for sudden cardiac
      death, because of the heterogeneous reduction in Ito, IK1, and ICaL. The
      excitation-contraction coupling is impaired because of the decrease in ICaL and
      Cav1.2 misalignment with respect to ryanodine receptor 2.

PMID- 25046858
TI  - Sudden death in adult congenital heart disease: risk stratification in 2014.
AB  - Arrhythmias and sudden death continue to plague a subset of adult patients with
      congenital heart disease. Despite investigative efforts spanning many decades,
      accurate identification of the high-risk patient remains challenging owing to a
      limited population size, relatively low event rate, and constantly evolving
      surgical approaches to the various malformations. Furthermore, until recently,
      most studies of the subject involved single-center formats with limited
      statistical power. The number of adult survivors has now reached a critical size
      where larger collaborative projects are beginning to generate more objective
      criteria for assessing risk. This review will provide an update on risk
      stratification for several of the major congenital cardiac lesions and outline
      the current recommendations for surveillance and management. 

PMID- 25046859
TI  - Searching for a Rosetta Stone: genetic data and clinical patient management.

PMID- 25046860
TI  - Intracellular pH responses in the industrially important fungus Trichoderma
      reesei.
AB  - Preserving an optimal intracellular pH is critical for cell fitness and
      productivity. The pH homeostasis of the industrially important filamentous fungus
      Trichoderma reesei (Hypocrea jecorina) is largely unexplored. We analyzed the
      impact of growth conditions on regulation of intracellular pH of the strain Rut
      C30 and the strain M106 derived from the Rut-C30 that accumulates L-galactonic
      acid-from provided galacturonic acid-as a consequence of L-galactonate
      dehydratase deletion. For live-cell measurements of intracellular pH, we used the
      genetically encoded ratiometric pH-sensitive fluorescent protein RaVC. Glucose
      and lactose, used as carbon sources, had specific effects on intracellular pH of
      T. reesei. The growth in lactose-containing medium extensively acidified cytosol,
      while intracellular pH of hyphae cultured in a medium with glucose remained at a
      higher level. The strain M106 maintained higher intracellular pH in the presence
      of D-galacturonic acid than its parental strain Rut-C30. Acidic external pH
      caused significant acidification of cytosol. Altogether, the pH homeostasis of T.
      reesei Rut-C30 strain is sensitive to extracellular pH and the degree of
      acidification depends on carbon source.

PMID- 25046861
TI  - The effect of Pleurotus ostreatus arabinofuranosidase and its evolved variant in
      lignocellulosic biomasses conversion.
AB  - The fungal arabinofuranosidase from Pleurotus ostreatus PoAbf recombinantly
      expressed in Pichia pastoris rPoAbf and its evolved variant rPoAbf F435Y/Y446F
      were tested for their effectiveness to enhance the enzymatic saccharification of
      three lignocellulosic biomasses, namely Arundo donax, corn cobs and brewer's
      spent grains (BSG), after chemical or chemical-physical pretreatment. All the raw
      materials were subjected to an alkaline pretreatment by soaking in aqueous
      ammonia solution whilst the biomass from A. donax was also pretreated by steam
      explosion. The capability of the wild-type and mutant rPoAbf to increase the
      fermentable sugars recovery was assessed by using these enzymes in combination
      with different (hemi)cellulolytic activities. These enzymatic mixtures were
      either entirely of commercial origin or contained the cellulase from Streptomyces
      sp. G12 CelStrep recombinantly expressed in Escherichia coli in substitution to
      the commercial counterparts. The addition of the arabinofuranosidases from P.
      ostreatus improved the hydrolytic efficiency of the commercial enzymatic
      cocktails on all the pretreated biomasses. The best results were obtained using
      the rPoAbf evolved variant and are represented by increases of the xylose
      recovery up to 56.4%. These data clearly highlight the important role of the
      accessory hemicellulolytic activities to optimize the xylan bioconversion yields.

PMID- 25046862
TI  - Aberrant EEG functional connectivity and EEG power spectra in resting state post
      traumatic stress disorder: a sLORETA study.
AB  - The aim of the present study was to explore the modifications of EEG power
      spectra and EEG connectivity of resting state (RS) condition in patients with
      post-traumatic stress disorder (PTSD). Seventeen patients and seventeen healthy
      subjects matched for age and gender were enrolled. EEG was recorded during 5min
      of RS. EEG analysis was conducted by means of the standardized Low Resolution
      Electric Tomography software (sLORETA). In power spectra analysis PTSD patients
      showed a widespread increase of theta activity (4.5-7.5Hz) in parietal lobes
      (Brodmann Area, BA 7, 4, 5, 40) and in frontal lobes (BA 6). In the connectivity
      analysis PTSD patients also showed increase of alpha connectivity (8-12.5Hz)
      between the cortical areas explored by Pz-P4 electrode. Our results could reflect
      the alteration of memory systems and emotional processing consistently altered in
      PTSD patients. 

PMID- 25046863
TI  - Dysregulation of nectin-2 in the testicular cells: an explanation of cadmium
      induced male infertility.
AB  - Nectin-2, a junction molecule, is found at the basal and apical ectoplasmic
      specializations (ES) for the formation of the blood-testis barrier (BTB)
      (constituted by tight junctions and basal ES) and Sertoli-spermatid adhesion.
      Loss of nectin-2 causes male infertility, suggesting nectin-2-based ES is crucial
      for spermatogenesis. Cadmium (Cd) has been known to induce severe testicular
      injury. Recent evidence has shown that the basal ES at the BTB and apical ES are
      the targets of Cd, suggesting that unique junction protein at the ES may explain
      why testis is more susceptible than other tissues. Since nectin-2 is expressed
      exclusively at the ES, it is highly possible that nectin-2 is the direct target
      of Cd. In this study, we investigate if nectin-2 is the target protein of Cd
      toxicity and the mechanism on how Cd down-regulates nectin-2 to achieve ES
      disruption. Our results revealed that Cd suppresses nectin-2 at transcriptional
      and post-translational levels. Inhibitor and shRNA knockdown have shown that Cd
      induces nectin-2 protein degradation via clathrin-dependent endocytosis.
      Immunofluorescence staining and endocytosis assays further confirmed that nectin
      2 internalization is promoted upon Cd treatment. Besides, Cd directly represses
      nectin-2 transcription. EMSA and ChIP assays showed that Cd inhibits the binding
      of positive regulators to nectin-2 promoter. siRNA and overexpression analyses
      have demonstrated that Cd reduces the expression and binding affinity of positive
      regulators for transcription. Taken together, nectin-2 is the direct molecular
      target of Cd and its disruptive effects are mediated via direct repressing nectin
      2 transcription and endocytosis of nectin-2 for degradation. 

PMID- 25046864
TI  - Nrf2 ameliorates diabetic nephropathy progression by transcriptional repression
      of TGFbeta1 through interactions with c-Jun and SP1.
AB  - Diabetic nephropathy (DN) is one of the major complications in diabetes patients.
      Reactive oxygen species (ROS) play key roles in DN progression. As a primary
      transcription factor, Nrf2 controls the antioxidant response to maintain cellular
      redox homeostasis. Herein we systemically examined the role of Nrf2 in DN
      progression and its regulatory mechanism in a mouse model bearing type II
      diabetes and in cultured human renal mesangial cells (HRMCs). We found that Nrf2
      could ameliorate DN progression by transcriptional repression of TGFbeta1 in vivo
      and in vitro. Moreover, Nrf2 bound to the specific region in TGFbeta1 promoter by
      interactions with transcription factors c-Jun and SP1. Significant abolishment of
      Nrf2-mediated TGFbeta1 transcriptional repression could be accomplished by
      knockdown of either c-Jun or SP1, and site-directed mutagenesis of c-Jun and SP1
      binding sites in the TGFbeta1 promoter specific region. Moreover, after
      interacting with c-Jun and SP1, Nrf2 inhibited c-Jun and SP1 activations, and
      thus reversed c-Jun- and SP1-promoted TGFbeta1 transcription. In all, Nrf2 could
      slow down DN progression by repression of TGFbeta1 in a c-Jun and SP1-dependent
      way. Our findings may provide novel clues for DN preventions and interventions in
      clinic. 

PMID- 25046865
TI  - The role of H3K4me3 and H3K9/14ac in the induction by dexamethasone of Per1 and
      Sgk1, two glucocorticoid [corrected] early response genes that mediate the
      effects of acute stress in mammals.
AB  - Glucocorticoids are known to induce or repress the expression of a wide variety
      of genes with roles in various biological processes such as the circadian clock
      and the stress response. We studied the changes in the levels of two histone H3
      post-translational modifications associated with active chromatin, H3
      trimethylated at lysine 4 (H3K4me3) and H3 acetylated at lysines 9/14
      (H3K9/14ac), that take place in the promoters of two glucocorticoid early
      response genes, Per1 and Sgk1, during their induction by the synthetic
      glucocorticoid, dexamethasone. Sgk1 mediates the effects of acute and chronic
      stress on the prefrontal cortex and other parts of the brain, while Per1 is a
      core circadian clock gene whose expression is strongly induced by the increased
      levels of blood-borne glucocorticoids that accompany acute and chronic stress.
      Here we show that dexamethasone rapidly increases the levels of H3K4me3 and
      H3K9/14ac in the promoters of both genes. Furthermore, the effect of
      dexamethasone on these genes, regarding both mRNA levels and the abundance of
      H3K4me3 and H3K9/14ac in their promoters, can be inhibited by the presence of
      nicotinamide, a metabolic molecule which has been shown to possess anxiolytic
      properties.

PMID- 25046866
TI  - Activity concentration of natural radioactive nuclides in nonmetallic industrial
      raw materials in Japan.
AB  - Natural materials such as rock, ore, and clay, containing natural radioactive
      nuclides are widely used as industrial raw materials in Japan. If these are high
      concentrations, the workers who handle the material can be unknowingly exposed to
      radiation at a high level. In this study, about 80 nonmetallic natural materials
      frequently used as industrial raw materials in Japan were comprehensively
      collected from several industrial companies, and the activity concentrations of
      (238)U series, (232)Th series and (40)K in the materials was determined by ICP-MS
      (inductively-coupled plasma mass spectrometer) and gamma ray spectrum analyses.
      Effective doses to workers handling them were estimated by using methods for dose
      estimation given in the RP 122. We found the activity concentrations to be lower
      than the critical values defined by regulatory requirements as described in the
      IAEA Safety Guide. The maximum estimated effective dose to workers handling these
      materials was 0.16 mSv y(-1), which was lower than the reference level (1-20 mSv
      y(-1)) for existing situation given in the ICRP Publ.103. 

PMID- 25046867
TI  - Quantified pH imaging with hyperpolarized (13) C-bicarbonate.
AB  - PURPOSE: Because pH plays a crucial role in several diseases, it is desirable to
      measure pH in vivo noninvasively and in a spatially localized manner. Spatial
      maps of pH were quantified in vitro, with a focus on method-based errors, and
      applied in vivo. METHODS: In vitro and in vivo (13) C mapping were performed for
      various flip angles for bicarbonate (BiC) and CO2 with spectral-spatial
      excitation and spiral readout in healthy Lewis rats in five slices. Acute
      subcutaneous sterile inflammation was induced with Concanavalin A in the right
      leg of Buffalo rats. pH and proton images were measured 2 h after induction.
      RESULTS: After optimizing the signal to noise ratio of the hyperpolarized (13) C
      bicarbonate, error estimation of the spectral-spatial excited spectrum reveals
      that the method covers the biologically relevant pH range of 6 to 8 with low pH
      error (< 0.2). Quantification of pH maps shows negligible impact of the residual
      bicarbonate signal. pH maps reflect the induction of acute metabolic alkalosis.
      Inflamed, infected regions exhibit lower pH. CONCLUSION: Hyperpolarized (13) C
      bicarbonate pH mapping was shown to be sensitive in the biologically relevant pH
      range. The mapping of pH was applied to healthy in vivo organs and interpreted
      within inflammation and acute metabolic alkalosis models.

PMID- 25046868
TI  - Instruction of hematopoietic lineage choice by cytokine signaling.
AB  - Hematopoiesis is the cumulative consequence of finely tuned signaling pathways
      activated through extrinsic factors, such as local niche signals and systemic
      hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage
      choice of hematopoietic stem and progenitor cells or are only selectively
      allowing survival and proliferation of already intrinsically lineage-committed
      cells has been debated over decades. Recent results demonstrated that cytokines
      can instruct lineage choice. However, the precise function of individual cytokine
      triggered signaling molecules in inducing cellular events like proliferation,
      lineage choice, and differentiation remains largely elusive. Signal transduction
      pathways activated by different cytokine receptors are highly overlapping, but
      support the production of distinct hematopoietic lineages. Cellular context,
      signaling dynamics, and the crosstalk of different signaling pathways determine
      the cellular response of a given extrinsic signal. New tools to manipulate and
      continuously quantify signaling events at the single cell level are therefore
      required to thoroughly interrogate how dynamic signaling networks yield a
      specific cellular response. 

PMID- 25046873
TI  - Health tips. Preventing cataracts.

PMID- 25046872
TI  - Cataract surgery.  Choose the time.

PMID- 25046874
TI  - Delaying retirement may reduce Alzheimer's risk.

PMID- 25046875
TI  - Stem cells grown in space may aid stroke treatment.

PMID- 25046876
TI  - Whole-food smoothies.  A potent blend of good nutrition.

PMID- 25046878
TI  - CHADS2 score.  Assessing stroke risk.

PMID- 25046877
TI  - Oxytocin.  The social hormone.

PMID- 25046879
TI  - I keep reading that nuts are good for health, but I also know they are high in
      fat and calories. If I'm watching my weight, should I be eating nuts?

PMID- 25046880
TI  - I recently received a cortisone injection in my knee, and it substantially
      reduced the pain and stiffness.  How often can I safely have these injections? 
      Will there be side effects?

PMID- 25046881
TI  - Serogrouping and pulsed-field gel electrophoresis analysis of Listeria
      monocytogenes isolates from cases of human infection in Hungary 2004-2012
      molecular typing of Listeria monocytogenes in Hungary.
AB  - Eighty isolates of Listeria monocytogenes cultured from human infections in
      Hungary between 2004 and 2012 were serotyped by the PCR technique of Doumithet
      al. [9] and characterised by pulsed-field gel electrophoresis (PFGE). Most of the
      isolates belonged to two serogroups: 53 isolates (66.3%) to serovar group
      4b,4d,4e and 21isolates (25.8%) to serogroup 1/2a,3a. Although many pulsotypes
      were identified a particular pulsotype proved highly excelling comprising of 31
      isolates after digestion by both ApaI and AscI restriction enzymes. All strains
      from this pulsotype belonged toserovar group 4b,4d,4e. Interestingly 24% of
      isolates from invasive samples(cerebrospinal fluid, blood) belonged to two
      distinct pulsotypes in the less common serovar group 1/2a,3a. Several small
      clusters of cases caused by isolates with identical pulsotypes were identified.

PMID- 25046883
TI  - Pathology of celiac disease: a brief review.
AB  - Celiac disease is a gluten or prolamine-induced immunological disorder primarily
      affecting the intestines. Celiac disease is often missed since not only are
      clinical findings 'not typical' but also because many cases are asymptomatic. The
      diagnosis is based on a constellation of clinical, serological and histological
      findings in a duodenal biopsy, in addition to HLA genotype.and response to a
      gluten-free diet.Although some guidelines suggest that histology may not
      mandatory in every case, by and large changes in mucosal biopsies of the duodenum
      still remain an important diagnostic tool. The evaluation of a duodenal biopsy
      requires a properly oriented and satisfactory hematoxylin & eosin stained
      paraffin section. A poorly oriented and technically suboptimal biopsy is not
      uncommonly the reason for erroneous interpretation. An increase in
      intraepithelial lymphocytes [IELs] and an alteration of the crypt: villus ratio
      forms the basis of diagnosis. These are semiquantitavely classified. Despite
      varying opinions related to the cut-off values of IELs and findings that
      recommend appropriate site, number and size of the biopsy specimens, the
      sensitivity of biopsies vary from 90%-100%. Interpretation of histological
      findings require correlation with other evidences since the changes in duodenal
      biopsy may be similar to those seen in a host of other diseases including
      tropical sprue. It must also be mentioned that in the Indian subcontinent is that
      reference values for normal duodenal biopsies are lacking, making interpretation
      difficult especially when changes are mild. Histological changes in the duodenal
      mucosa often take months to normalize after clinical remission. This is a review
      of various aspects related to the histological changes in duodenal mucosal
      biopsies that aid in the diagnosis and follow-up of cases of celiac disease.

PMID- 25046882
TI  - Effect of dentin powder on the antimicrobial properties of hyperpure chlorine
      dioxide and its comparison to conventional endodontic disinfecting agents.
AB  - INTRODUCTION: Previously we found that the high purity chlorine-dioxide(ClO2) has
      a very potent disinfectant efficacy on oral pathogenic microorganisms and as a
      root canal irrigant it is able to eliminate the experimental Enterococcus
      faecalis(E. faecalis) infection from the root canal system. This study examines
      whether the presence of dentin powder influences the antibacterial efficacy of
      ClO 2. METHODS: In an in vitro dentin powder model the following irrigants were
      tested against planktonic E. faecalis: 2% chlorhexidine (CHX), 2.5% sodium
      hypochlorite (NaOCl), 0.12%ClO2 (Solumium) and one local root canal medicament:
      saturated Ca(OH)2. Survival of bacteria exposed to agents without and with human
      dentin powder or preincubated with dentin powder was investigated. The effect of
      the dentin powder on ClO2 concentration was investigated by titrations. RESULTS:
      Without dentin powder ClO 2 killed all E. faecalis and delivered the best result
      already after 1 minute; however, after longer contact time with dentin the
      difference between the disinfectants disappeared. The presence of dentin powder
      decreased the concentration of ClO 2 and attenuated the antibacterial efficiency
      of ClO2 and Ca(OH)2, but did not decrease of CHX and NaOCl.Preincubation with
      dentin powder caused significant loss of antibacterial activity of all
      investigated agents, ClO2 and Ca(OH)2 having the highest reduction. CONCLUSION:
      As the presence of dentin powder had a negative effect on the efficacy of
      disinfectants, the importance of elimination of dentin scrapings and smear layer
      from the root canal system during endodontic treatments is highly recommended.
      ClO 2 can be effective for a final rinse.

PMID- 25046884
TI  - Prevalence and assessment of role of SEN virus in acute and chronic hepatitis in
      India.
AB  - BACKGROUND AND AIM: SEN virus (SENV), is a recently discovered single-stranded
      DNA virus of Annelloviridae family and is believed may play a role in non A-E
      hepatitis. We conducted this study to identify the prevalence and clinical
      association of SENV with acute and chronic hepatitis. METHODS: 135 liver disease
      patients were studied. Extent of liver damage was assessed using the Model for
      End Stage Liver Disease (MELD) score. A-E viruses and HIV were detected by enzyme
      immunoassay. Nested PCR was performed for detection of SENV and its genotypes D
      and H. RESULTS: 34 cases (25.18%) were positive for SEN virus DNA, a
      statistically significant finding (p < 0.01) of which 22 (64%) had acute viral
      hepatitis, 4 (11.76%) had chronic viral hepatitis, 3 (8.82%) fulminant hepatic
      failure and 5 (14.70%) cirrhosis. Mean AST was 47.85 IU/L, ALT 51.2 IU/L and INR
      1.73, mean MELD score was 18.38 (11 to 24). 17.64% had severely deranged MELD
      score. SENV-D genotype was detected in 13 (38%) and SENV-H in 19 (58%) cases.
      SENV-H occurred in both acute (53%) and chronic hepatitis (47%). SENV-D was
      strongly associated with acute hepatitis (85%). Cirrhotic and FHF cases were SENV
      H positive. 12 (44.11%) were co-infected with HBV, 5 (14.7%) with TTV, 4(11.76%)
      with HEV, 2 (5.88%) with HCV and 5 (14.4%) with HIV. CONCLUSION: Significant
      prevalence of SENV in hepatitis patients was observed. On the basis of clinical
      findings and abnormal liver function tests, we conclude that SENV appears to be
      not only hepatotropic but also capable of liver damage. Higher prevalence of SENV
      H in cirrhotics may point to its possible role in the development of cirrhosis.

PMID- 25046885
TI  - Intrarenal resistance index (RI) as a predictor of early renal impairment in
      patients with liver cirrhosis.
AB  - BACKGROUND: Despite its functional nature, hepatorenal syndrome (HRS) is
      associated with a poor prognosis and the only effective treatment is liver
      transplantation. It is very important to diagnose renal impairment in cirrhosis
      patients at an early stage before overt HRS develops. In patients with cirrhosis
      the early renal impairment or renovascular vasoconstriction can be predicted by
      renal arterial resistance index (RI). Our study aimed to compare RI in healthy
      controls versus patients with liver cirrhosis with and without ascites and assess
      its value for predicting subsequent renal status. METHODS: Patients were divided
      into 2 groups with 50 patients in each group. Group 1 contained patients with
      cirrhosis without ascites and group 2 contained cirrhosis patients with ascites.
      All patients were subjected to detailed clinical examination, laboratory
      investigations and abdominal doppler ultrasound with renal RI measurements.
      Patients were followed for 6 months. RESULTS: RI was significantly higher in
      cirrhotic patients as compared to healthy controls (0.62 vs. 0.52, p< 0.01). In
      patients with cirrhosis, RI was significantly greater in patients with ascites
      than those without ascites (0.70 vs. 0.62, p < 0.01). RI >0.70 was significant
      independent predictor of subsequent HRS development (p = 0.006) CONCLUSIONS:
      Intrarenal RI measurement can be used as a predictor of HRS and may be further
      validated for regular monitoring of cirrhotic patients at risk of developing
      renal impairment.

PMID- 25046886
TI  - Small bowel histomorphology in surgical complications of ascariasis: a small
      series.
AB  - BACKGROUND: Ascariasis is a worldwide health problem. Patients usually get
      treated with antihelminthics. Rarely, undiagnosed cases can present with surgical
      complications. AIM: To study the clinico-pathological characteristics of small
      bowel specimens of patients presenting with surgical complications of ascariasis.
      METHODS: This is a retrospective analysis of small bowel specimens of patients
      presenting with surgical complications of ascariasis from a period of 2010 to
      2012, received in our department. RESULTS: The patients were of all age groups
      and mainly presented with intestinal obstruction and perforation. Transmural
      gangrenous change was seen in all nine cases. Encysted ova were seen in five
      cases. Two of the cases showed partial to complete infarction of isolated
      mesenteric lymph nodes. CONCLUSION: Ascariasis may cause transmural gangrene of
      bowel as well as mesenteric lymph node infarction.

PMID- 25046887
TI  - Helicobacter pylori infection in children in Madagascar: risk factors for
      acquisition.
AB  - AIM: The aim of our study was to assess the prevalence, risk factors for
      acquisition and the clinical characteristics of H. pylori infection in Malagasy
      children. METHODS: A 2 year prospective study was conducted among 434 children
      from a rural (group A) and an urban area (group B). H. pylori status was
      evaluated by an ELISA serological test. Various demographic and clinical
      characteristics were recorded and subjected to statistical analysis. RESULTS: The
      prevalence of H. pylori infection was 39.6% and increased significantly from
      18.1% for children <1 year old to 61.5% for children >10 years old. It was
      significantly higher in group B (46.9%) than in group A (26.4%). Using
      multivariate logistic regression modelling, a significant association was found
      between H. pylori infection and drinking spring water. Exposure to antibiotics
      during the previous year had no observable effect on H. pylori. CONCLUSION: The
      overall prevalence of H. pylori infection among Malagasy children was 39.6%. A
      significant association between H. pylori infection and drinking spring water was
      found.

PMID- 25046888
TI  - Retrospective and prospective validation of model for end-stage liver disease
      (MELD) score in predicting mortality in patients of alcoholic liver disease.
AB  - BACKGROUND AND AIM: Patients with alcoholic hepatitis and alcoholic cirrhosis
      have significant morbidity and mortality. The model for end-stage liver disease
      (MELD) score is used to predict mortality in patients with liver disease. Our
      study aimed to validate the utility of MELD score versus Child Pugh Turcotte
      (CPT) and modified CPT (CPT+creatinine; CPTC) scores in predicting mortality
      among alcoholic liver disease (ALD) patients. METHODS: We examineda retrospective
      (n=110; mean age 44.5years; 109 men) and a prospective (n=96; mean age 45 years;
      92 men) cohort of patients suffering from ALD, with varying disease severity, and
      compared the ability of MELD, CTP and CPTC scores to predict the 1-, 3- and 6
      month mortality using concordance (c-) statistics. RESULTS: The median MELD, CPT
      and CPTC scores were 21, 10 and 11 in the retrospective group and 21, 10 and 10
      in prospective groups, respectively. The 1-month, 3-month and 6-month mortality
      was 41 (37.3%), 59 (53.6%) and 81 (73.6%) in the retrospective group and 27
      (28.1%), 41 (42.7%) and 65 (67.7%) in the prospective group. The predictive
      ability of MELD, CPT and CPTC was 0.72, 0.67, 0.68 for 1-month mortality, 0.73,
      0.70, 0.68 for 3-month mortality and 0.83, 0.75, 0.73 for 6-month mortality in
      retrospective group and 0.86, 0.56, 0.63 for 1-month mortality, 0.80, 0.57, and
      0.60 for 3-month mortality, and 0.88, 0.51, and 0.64 for 6-month mortality in the
      prospective cohort, respectively. The predictive accuracy of MELD was
      significantly better than CPT and CPTC scores in the prospective group.
      CONCLUSIONS: MELD is a valid prognostic score compared to CPT and CPTC scores for
      predicting short-term mortality in patients of alcoholic liver disease.

PMID- 25046889
TI  - Extended multiorgan resection in locally advanced gastric cancer: a single centre
      experience from south India.
AB  - BACKGROUND: The prognostic and survival benefit of extended multiorgan resection
      for locally advanced gastric adenocarcinoma remains controversial. The morbidity
      associated with additional organ resection has been found to be higher when
      compared to patients undergoing gastrectomy alone. The aim of our study was to
      evaluate the morbidity, mortality and survival benefit associated with extended
      multiorgan resection for locally advanced gastric adenocarcinoma. METHODS: From
      January 2004 to December 2011, 721 patients underwent resectional surgery for
      gastric adenocarcinoma at the Christian Medical College, Vellore, India. Out of
      this group, 36 patients underwent primary resection and had one or more organs
      resected in addition to the stomach. A retrospective analysis of the case records
      of all these patients was performed. The Kaplan-Meier survival probability was
      estimated. Cox regression analysis was used to evaluate the clinico-pathological
      variables affecting the survival of these patients. RESULTS: The perioperative
      morbidity and mortality rates were 25% and 5.5% respectively. The most common
      organs resected were colon and spleen. The incidence of pathologically confirmed
      T4b cancers was only 50%. The median survival of these patients was 28 months.
      The survival was influenced by a R0 or curative resection. However, it was not
      statistically significant. CONCLUSION: Extended multiorganresection in locally
      advanced gastric cancer can be performed with acceptable morbidity and mortality.
      In our study, overstaging was found in 50% of the patients and hence, when the
      real nature of invasion is unclear, the surgeon may proceed with en bloc
      resection of the stomach with the involved adjacent organs. As long as an R0
      resection can be achieved, extended multiorgan resection can be performed for
      carcinoma stomach.

PMID- 25046890
TI  - Two different diagnoses in one radiological imaging, related or not?

PMID- 25046892
TI  - Ischiorectal abscess presenting as paralytic ileus.

PMID- 25046891
TI  - Peritoneal ascariasis presenting as granulomatous peritonitis and omental cyst.

PMID- 25046893
TI  - 'Umbrella sign' in computerized tomogram to differentiate giant greater omental
      cyst from ascites.

PMID- 25046894
TI  - Gastric trichobezoar: a diagnostic tangle.

PMID- 25046895
TI  - Barium emesis during barium enema study: a definitive sign of gastrojejunocolic
      fistula.

PMID- 25046897
TI  - Systemic Wangiella dermatitidis infection presenting as liver mass and
      obstructive cholangiopathy.

PMID- 25046896
TI  - Acquired nonspecific cicatrizing inflammation causing pyloric stricture and
      gastric outlet obstruction in infancy: is it Jodhpur disease?

PMID- 25046898
TI  - 'H' graft pancreaticoduodenal-caval shunt in a patient with extrahepatic portal
      venous obstruction with ectopic variceal bleed.

PMID- 25046899
TI  - Unsuspected mixed invasive intestinal mycosis in an infant with metabolic
      disorder.

PMID- 25046900
TI  - Abdominal tuberculosis masquerading as intestinal lymphangiectasia.

PMID- 25046901
TI  - Spontaneous cutaneous fistulization, eventration of right hemidiaphragm and
      invasion of the pericardial cavity by a liver hydatid cyst.

PMID- 25046902
TI  - Capturing the zest of the best.

PMID- 25046904
TI  - Clinicians in contact home and away.

PMID- 25046903
TI  - Ten years of foundation trusts. 'An irreversible shift in power was overdue'.

PMID- 25046905
TI  - Telehealth. Remote control of care. Monitoring patients with chronic conditions
      in.

PMID- 25046906
TI  - Patient experience. Quick decisions mean a quick exit.
AB  - Patients admitted to A&E in the evening can stay in hospital up to four days
      longer than morning admissions. Trusts can take targeted action during the
      assessment phase to reduce patient stays, explain Seamus McGirr and colleagues

PMID- 25046907
TI  - Acute care. Time to throw away A&E targets.

PMID- 25046908
TI  - On the difference between beauty and goodness [1933].

PMID- 25046909
TI  - Concentrated attention and dreaming [1951].

PMID- 25046911
TI  - [The great usurpation or how non-art was substituted for art].

PMID- 25046910
TI  - Feeling or thought--both or neither? A short review.

PMID- 25046912
TI  - [Contribution of the Alsace natural sciences in Poland & Lithuania in the late
      eighteenth and early nineteenth century: Jean Hermann, Jean-Louis Graffenauer &
      Louis-Henri Bojanus].

PMID- 25046913
TI  - [Strasbourg and its university seen by a Polish student on the eve of the
      Revolution].

PMID- 25046914
TI  - [Memories of a student at the University of Strasbourg (1783-1793)].

PMID- 25046915
TI  - Emigration of mathematicians from Poland in the 20th century (roughly 1919-1989).

PMID- 25046916
TI  - A life in the academia unusually shaped by war and exile. An autobiography.

PMID- 25046917
TI  - A closer look at the popularization of science in Poland during the Stalinist
      period. The magazine Problemy, 1945-1956.

PMID- 25046918
TI  - [Hi-tech health care: modern status and prospects of development in medical
      facilities of the Ministry of Defence].
AB  - The article is devoted to the current issues of providing hi-tech medical care in
      hospitals of the Ministry of Defence. Since the beginning of 2013 the executive
      body of the Russian Ministry of Defense pays special attention to improvement of
      the quality and accessibility of health care contingent of the Ministry of
      Defence. Thus, according to decision of the Minister of Defense of the Russian
      Federation, General of the Army Sergei Shoigu in 2013 more than 1.1 billion
      rubles (in 2012, targeted funding of high-tech medical care in the Ministry of
      Defence did not materialize) was allocated for military medical institutions of
      the Ministry of Defense of the Russian Federation to provide high-tech medical
      care. As a result, in 7 months in 2013 the volume of medical care has increased
      by 32% in comparison with the same period in 2012. Currently the main military
      medical department of the Ministry of Defense is working to resolve the order of
      delivery and financing hi-tech medical care in the Armed Forces in the following
      areas: inclusion of military medical institutions of the Ministry of Defence in
      the list of health organizations, providing high-tech medical care, approved by
      Order of the Ministry of Health of the Russian Federation, legal regulation of
      the provision of high-tech medical care in military medical establishments of the
      Ministry of defense of the Russian Federation within the budget appropriation
      allocated to the Ministry of Defence.

PMID- 25046919
TI  - [Marketing in the system of military-medical facilities].
AB  - Military medical facilities of the Ministry of Defence of the Russian, have
      received the right to provide additional services and have been involved in the
      sphere of market relations. The strong influence of market relations - an
      objective reality that must be used for the development of military medical
      institutions and improving quality of care.Effective commercial activity can
      improve capabilities of the military medical institutions. This requires constant
      study of market mechanisms to implement and develop their competitive advantage.
      The paper substantiates the need for the participation of military medical
      institutions in the provision of health services to the public on the terms of
      compensation incurred by financial institutions costs (paid medical services,
      medical assistance program of compulsory and voluntary health insurance). Taking
      into account the specifics of military medical institutions set out basic
      principles and recommendations have been implementing marketing approach in their
      management, the practical application of which will not only increase efficiency,
      but also create conditions to improve the financial and economic indicators. This
      knowledge will help the mechanism of functioning health care market and the rules
      of interaction of market counterparties.

PMID- 25046920
TI  - [Modern capabilities of laparoscopic surgery for kidney cancer treatment].
AB  - Retroperitoneal surgical approach is the main component of operative
      intervention. This approach predetermines quality of surgical operation and the
      risk of intraoperative complications, an opportunity of their prevention.
      Lymphadenectomy is the unique method allowing authentically to confirm cancer in
      the lymph nodes and to evaluate a stage of disease. Endoscopicsurgical
      nephrectomy is the operation that keeps advantages of minimally invasive surgical
      approach in the majority of kidneys diseases without loss of quality of surgical
      treatment.

PMID- 25046921
TI  - [Systematization of primary headache: current and future prospects].
AB  - The article is devoted to the current state of the problem of systematization of
      primary headaches and main clinical forms. The conceptual evolution of ideas
      about the classification of certain options of cephalgia and identified major
      trends for its improvement is given. Verification of types and subtypes of
      individual cephalgia can present a significant challenge even for experienced
      neurologists, neurosurgeons, and internists. In this regard in most European
      countries and the US. have set up specialized centers for the treatment of
      headaches. Concluded that in the short term in the national health care system,
      including. Including the Armed Forces, it is advisable to create such centers.

PMID- 25046922
TI  - [Structure and antibiotic resistance of urinary tract pathogens in case of
      infection in young patients under the conditions of North].
AB  - For the purpose of optimization of antibacterial treatment of urinary tract
      infection in 700young patients under the condition of North it was examined the
      responsivity of urinary tract pathogens to antibiotics in 1998-2009. The most
      effective group of antibiotics is revealed. The most frequent types of urinary
      tract pathogens are: in men - S. epidermidis, S. saprophyticus, S. aureus; in
      women with non-complicated UTI - E. coli, S. epidermidis, S. saprophyticus u S.
      aureus; with complicated - E. coli, S. saprophyticus, S. epidermidis. The
      abovementioned pathogens showed the low antibiotic resistance (in vitro) to
      gentamicin and ofloxacin; high antibiotic resistance to cephalosporin (3rd
      generation) and ciprofloxacin. It is better to prescribe ofloxacin and cefotaxime
      for patients with complicated UTI; for women with non-complicated UTI - ofloxacin
      and ceftriaxone. It is necessary to consider nephrotoxicity and low compliance
      before prescription of gentamicin.

PMID- 25046923
TI  - [Osgood-Schlatter disease in military personnel].
AB  - Clinical and radiological manifestations and outcomes of Osgood - Schlatter
      disease in 141 serviceman held military service are presented. Patients had the
      late stage of disease. Authors describe four options of radiological signs.
      Indications for surgical treatment are substantiated. Proved traumatic nature of
      the disease in the adolescent growth period. Analysis of observational data
      allows us to conclude that the primary manifestations of trauma of shinbone area
      can occur in patellar ligament and apophasis of shinbone. In old cases of Osgood
      Schlatter disease location and nature of the damage can be determined by
      hystotope analysis. This disease is one of the manifestations of heterotopic
      ossification.

PMID- 25046924
TI  - [The main ways of improvement of medical support of the Air Forces in modern
      conditions].
AB  - Blaginin A.A., Grebenyuk A.N., Lizogub LN. - The main ways of improvement of
      medical support of the Air Forces in modern conditions. Aircrew conducting active
      hostilities suffers from the whole spectrum of factors and conditions of the
      combat situation. The main task for the medical service of the Air Force is to
      carry out preventive and curative action for aviation specialists who are
      responsible for the combat capability of aircraft formations. The medical service
      of the Air Force must have forces and facilities for planning, organization and
      implementation of the treatment of lightly wounded and sick aviation
      professionals with short periods of recovery, medical rehabilitation of aircrew
      qfter suffering injuries, diseases, sanatorium therapy of aircrew with partial
      failure of health, outpatient and inpatient medical examination aircrew - flight
      commissions, preventive rest of aviation specialists with symptoms of chronic
      fatigue. Should be trained aviation physicians, including both basic military
      medical education and in-depth study of the medical aspects of various fields of
      personnel of the Air Force.

PMID- 25046926
TI  - [Improvement of the system of medical equipment rationing for military units in
      peacetime].
AB  - We present characteristics of a new regulatory act issued by the Ministry of
      Defense of the Russian Federation - Medical equipment supply rate for large
      units, military units and facilities of the Armed Forces of the Russian
      Federation in peacetime, prepared in the course of modernization of the system of
      medical equipment rationing. New system of medical equipment rationing answers
      modern requirements of the Armed Forces. Introduction of modern norms of medical
      supply into practical activities of military regulatory bodies, medical units,
      military units and organizations will increase the effectiveness and quality of
      medical service, will help to maintain servicemen's health and will facilitate
      the combat readiness of medical units.

PMID- 25046925
TI  - [Delivery of surgical care on naval ships: formation, development, and current
      stage].
AB  - Acute surgical diseases were and remain one of the most important problems of the
      organization of medical care and treatment of patients in the conditions of long
      distant sea voyage, when there is no possibility for medical evacuation. We
      analyzed the positive experience of surgical care in the sea, gained by Soviet
      and then and by Russian Navy physicians. As we haven't registered significant
      changes in morbidity of Navy crewmembers, we think that studying and creative
      application of this experience will have the positive effect.

PMID- 25046927
TI  - [The modern sources for making a medical geography description].
AB  - The current article is dedicated to application of Internet for acquisition of
      medical geography information. The vast majority of the modern domestic reference
      manuals are neither reliable nor up-to-date. At the time when the foreign printed
      sources are not easily accessible the foreign web resources often become the main
      source of information. The article possesses some practical advice on how to find
      the general, medical and military medical data on the web. It is emphasized the
      necessity of careful cross validation of all the obtained data to be confident in
      their reliability.

PMID- 25046928
TI  - [Sanitary and epidemiological supply for the Russian Army during the First World
      War (1914-1918)].
AB  - At the beginning of the First World War the most typical diseases in the Russian
      Army were typhoid, typhus, diphtheria, cholera, smallpox and other infectious
      diseases. At the beginning of the First World War the level of infectious
      morbidity was significantly low, but further increased and pandemic risk arose.
      Servicemen were mostly ill with typhus, relapsing fever, flux, cholera, smallpox
      and typhoid. The highest mortality rate was registered in patients with cholera,
      typhus and typhoid. According the prewar deployment program of the Russian Army
      anti-epidemiologic facilities were established. By the end of war were
      established 110 sanitary-and-hygienic and 90 disinfection units. However,
      organization of anti-epidemiologic security was unsatisfactory. Due to lack of
      specialists and equipment anti-epidemiologic facilities of units were under
      strength. Commanders of sanitary units and sanitary service had not enough
      resources for operational service in the Forces and facilities of rear area.

PMID- 25046929
TI  - [Prophylaxis of substance abuse in the Armed Forces: organization and performance
      of screening. Problem of substance dependence disorders is the actual for many
      countries in the world and affects on health of servicemen].
AB  - Due to this fact specialists underline the necessity of implementation of
      constant drug testing system of servicemen. The most effective researches
      individuals suffering from substance abuse are sample and control survey.
      Promising areas of prevention of addictive disease include the use of modem
      technologies for early detection of drug narcotic drugs and psychotropic
      substances, using the psychophysiological and laboratory techniques. The most
      common rapid laboratory procedure is the use of test strips (tablets) based
      immunoassay analysis. To facilitate the evaluation of the results is increasingly
      incorporated hardware and software systems based on photometric detection. The
      work done on the testing of such complexes allowed us to determine the algorithm
      of screening soldiers to assess the effectiveness of various hardware and
      software systems and identify promising technologies to identify individuals with
      addictive disorders.

PMID- 25046930
TI  - [Experience of medical backup of military parade on Red Square. Authors showed
      data about medical backup of military personnel taking part in the parade on Red
      Square dedicating to anniversary of victory in the Great Patriotic War].
AB  - Authors showed data about medical backup of military personnel taking part in the
      parade on Red Square dedicating to anniversary of Victory in the Great Patriotic
      War. Experience of running such events allowed to work out an algorithm for
      medical service: preparatory stage, training stage, running of parade, stage of
      move out to permanent base. During the parade on Red Square for medical care
      asked 18 people (participants of parade and civilians). Authors came to
      conclusion that as a result of medical backup of military personnel taking part
      in the parade no infectious and group diseases were registered.

PMID- 25046931
TI  - [Experience of application of modern means of disinfection of air for preventive
      medications for respiratory diseases in troops].
AB  - Among factors of acute respiratory diseases morbidity in military personnel one
      of most important is frequent interfuisions, of military personnel and long-term
      occupancy in barracks in conditions of overcrowding. These factors conduce
      accumulation and communication of causative agents. Prophylaxis focused on
      prevention ofaerogenous transmission of infection. It is very important if
      ventilation in barracks is ineffective. Principally new possibilities of air
      sanitation in barracks are aerosol generators. Application of these generators
      unlike standard disinfection method provides massive exposure of fine aerosol to
      rooms. Authors highlight successful experience ofaerosol generators type Raster
      ULV that helped to reduce acute respiratory diseases morbidity in military
      personnel.

PMID- 25046932
TI  - [Modem information technologies for analysis of health status of military
      personnel].
AB  - Analysis of health status of military personnel is carried out in the interests
      of optimizing medical support personnel, maintaining a high level of health of
      servicemen, reducing morbidity. To perform this analysis it is necessary to
      compile materials about health status and morbidity in servicemen received from
      medical records. Selected data from medical records produced by mechanical
      summation of homogeneous diagnoses and time consuming. Today we have an
      opportunity to use common software for registration and result indices. So, by
      using the Excel program of Microsoft Office 2010, it is possible to implement the
      procedure for obtaining summary data from the electronic versions of documents
      medical records. By using the proposed algorithms allow authors to link the troop
      significantly optimize the process of accumulation, storage and use for analysis
      of the military - medical information, make the whole process of analysis of
      morbidity faster and more efficiently.

PMID- 25046933
TI  - [Safety criteria for blood refusion in military field surgery and trauma
      surgery].
AB  - Massive intracavitary hemorrhage in case if severe concomitant injury is the most
      frequent cause of death. Necessity of blood loss replacement requires effective
      and safe methods. One of them is blood reinfusion - technically less complicated
      method. The article shows advantages of using the hardware and filtration methods
      of blood sampling and reinfusion, developed scale rapid diagnosis of the level of
      hemolysis of autologous blood. Using of the method of filtration blood sampling
      provides 2X minimal amount of free hemoglobin than using an aspirator and
      reinfusion of blood with the contents therein to free hemoglobin 2.0g/ L prevents
      the risk of developing the syndrome and massive blood transfusion reduces the
      incidence of deaths at 11%. In patients with massive intracavitary hemorrhage it
      is advisable to use the method of semi-quantitative rapid analysis of free
      hemoglobin color scale.

PMID- 25046934
TI  - [Applying of assessment scales for patients with severe community-acquired
      pneumonia in young patients].
AB  - One of the most important issues in the management of patients with community
      acquired pneumonia is the correct initial assessment of the severity of the
      patient's condition. In the context of outbreaks of pneumonia among soldiers
      performing military service, this position is crucial. Up to date specialized
      scales were developed and used in clinical practice allowing assessing a risk on
      the basis of an adverse outcome, objectifying the decision on the choice of the
      place of treatment of a patient with community-acquired pneumonia. Various
      prognostic scales have their advantages and several disadvantages; in particular
      the possibility of their use to date has not been studied in the management of
      patients with pneumonia of organized groups. This publication is a brief
      description and analysis of the possibilities of applying the most well known
      scales in young people.

PMID- 25046935
TI  - [Alcoholic liver disease: possibilities of diagnosis, treatment and
      rehabilitation in multidisciplinary hospital].
AB  - Tactics of alcoholic liver disease treatment is defined in accordance with lesion
      level. Differentiated approach to these patients can significantly improve the
      efficiency of diagnosis, treatment and rehabilitation. At the stage of cirrhosis
      it is necessary to focus on prevention and treatment of complications. Patients
      with compensated cirrhosis and subcompensated improved survival achievable
      Propafenone S-ademetionine (geptral, Geptor). The article presents the results of
      our study demonstrating a significant decrease in serum bilirubin in patients on
      background intravenous S-ademetionine. Practicability of stage system creation of
      medical rehabilitation of patients with alcoholic cirrhosis is approved.

PMID- 25046936
TI  - [Capabilities of stress echocardiography in diagnosis of cardiovascular pathology
      and estimation for military service].
AB  - Annually about 6,5 thousands of military servicemen retire due to cardiovascular
      diseases, every second serviceman retires before superannuation. Stress
      echocardiography in comparison with other imaging studies is cheaper, safer and
      matches in sensibility and specificity. The prevalence of stress echocardiography
      and stress systems can make it available in district, central and main hospitals,
      and clinics of the Kirov Military Medical Academy. It is proposed to expand
      indications for stress echocardiography for certain contingent soldiers: those
      senior commanders, aircrew, and divers soldiers at high risk of cardiovascular
      complications. For training of specialists in the filed of stress
      echocardiography in the Kirov Military Medical Academy themed cycles for medical
      ultrasound and functional diagnostics are orginised.

PMID- 25046937
TI  - [The network organization of medical research in the US Armed Forces].
AB  - The current article is dedicated to the network mode of medical scientific
      research organization in the US Armed Forces exploring the Armed Forces Institute
      of Regenerative Medicine as an example. The following features of the institute
      are examined: the structure, definition of scientific research goals and tasks,
      financing, management, areas of research, the next generation of the institute.
      In conclusion some characteristic features of network scientific research
      establishment and required legal conditions are determined.

PMID- 25046938
TI  - [Disease control on the Russian fleet in XVIII century].
AB  - Disease control in domestic fleet in XVIII century was a part of government
      measures concerning protection of the territory of the Russian Empire from the
      penetration of dangerous infectious diseases. Understanding the role fleet could
      play in the spread of infection, the government sought to prevent its entry from
      the sea. Following this task, in the early 20-s of XVIII century on islands of
      the Gulf Seskar and Wolf organized sanitary quarantine stations where ships from
      unfavorable in relation to the epidemic areas stayed before they pester the
      Russian shore. Eventually when the Black Sea Fleet was created, similar items
      appeared in Ochakov, Sevastopol, Feodosia, Yalta and Kerch. In XVIII century
      health legislation was supplemented by a number of regulations relating to the
      activities of the fleet. In particular, during the reign of Peter I epidemic
      rules were composed, which, as it became known, lasted for about sixty years. In
      1786, the band released a set of quarantine rules designed to streamline the work
      of sanitary and quarantine stations. Important for protection against the
      penetration of Russian borders infectious diseases had timely warning of
      epidemics broke out abroad. Cooperating with European countries in the prevention
      and control of communicable diseases, Russia has successfully developed methods
      antiepidemic protection.

PMID- 25046939
TI  - [Phaleristics of Sisters of Charity].
AB  - In 1912 International Committee of the Red Cross and Red Crescent established a
      medal in honor of Florence Nightingale, still the most honorable award for
      nurses. In our country, there are no separate awards for nurses, they are awarded
      in the system of national awards, but medical authorities, major military medical
      institutions and public organizations have developed their own system of awarding
      the best nurses. Reader offered some graphic images of existing award marks
      contained documents revealing the mechanism of premium policy for the most
      distinguished in nursing health professionals.

PMID- 25046941
TI  - [Research and practice course cardiovascular surgery for field surgeons, in Ulm].

PMID- 25046940
TI  - [Prospects of development of pharmacy and pharmaceutical practice in military
      health care].

PMID- 25046942
TI  - [General integral medicine: the strategic direction for complex health
      interventions].
AB  - Nowadays, the simple combination of Western medicine (WM) and complementary and
      alternative medicine (CAM) cannot resolve all the health problems and various
      requirements. This article proposed the general integral medicine (GIM)
      theoretical model, which declares the disease causes analysis, clinical
      intervention and outcomes assessment should be recognized, managed and evaluated
      both from physiological, psychological, and spiritual status, and all the four
      dimensions: orthodox medicine (WM, Chinese medicine, etc.), individual inherent
      characteristics (emotion, attitude, psychology, etc.), cultural influences
      (doctors, caregivers, groups care, etc.), and natural environment and social
      systems (economic status, social security system, environmental pollution, etc).
      As for health outcomes assessment, a more comprehensive system including
      biological, doctors, patients, health intimate, social and environmental
      evaluations were required. The GIM model has individualized, dynamic,
      standardized, objective, systematic inherent characteristics, and opening and
      compatible external characteristics. It aims to provide the new theoretical
      guidance and strategic development direction for complex health interventions,
      and solve various medical related psychological and social problems.

PMID- 25046943
TI  - [Vegetarian diets and cardiovascular health: evidence-based and pondering].
AB  - The correlation between vegetarian diets and cardiovascular health is always one
      of the hotspots. Many scholars have performed so many clinical researches all
      over the world, providing evidence-based medicine (EBM) reference for clarifying
      their correlation. In this paper, we raise ideas and expectation on the basis of
      a Meta-analysis about vegetarian diets and blood pressure (published on JAMA
      Internal Medicine in Feb 2014) in combination of main clinical research
      literature in this field in recent 20 years.

PMID- 25046944
TI  - [Treating irritable bowel syndrome with diarrhea patients by yigan fupi
      decoction: a randomized controlled trial].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Yigan Fupi Decoction (YFD) in
      the treatment of irritable bowel syndrome with diarrhea (IBS-D) patients.
      METHODS: A randomized controlled clinical trail was carried out in patients with
      IBS-D. All patients were randomly assigned to the treatment group (58 cases,
      treated with YFD) and the control group (58 cases, treated with Pinaverium
      Bromide Tablet). The treatment course was 4 weeks for all patients. The total
      effective rate, the stool property and state, the quality of life (QOL), and TCM
      syndrome efficacy were assessed by IBS bowel symptom severity scale (IBS-BSS),
      IBS defecation state questionnaire (IBS-DSQ), IBS quality of life questionnaire
      (IBS-QOL), and traditional Chinese medicine pattern curative effect scoring
      system (TCM-PES) before and after treatment. RESULTS: There was no statistical
      difference in the total effective rate between the two groups (82.76% vs. 77.59%,
      P > 0.05). The treatment group was superior in the total IBS-BSS integral to the
      control group (P < 0.05). The total effective rate of improving the stool
      property was better in the treatment group than in the control group (81.03% vs.
      72.41%, P < 0.05). Besides, the number of days for emergent defecation among 10
      days was less in the treatment group than in the control group (P < 0.05). The
      improvement of the total IBS-QOL integral and the total integral of TCM syndrome
      were better in the treatment group than in the control group (P < 0.01). The
      total effective rate of TCM-PES was better in the treatment group than in the
      control group (84.48% vs. 70.69%, P < 0.05). CONCLUSION: YFD was effective in the
      treatment of IBS-D patients of Gan-qi invading Pi syndrome, and could effectively
      relieve bowel symptoms, improve the stool property and the defecation frequency,
      elevate their QOL, and attenuate Gan-qi invading Pi syndrome with favorable
      safety and compliance.

PMID- 25046945
TI  - [Effect of shenhuang ointment in promoting the rehabilitation of postoperative
      gastrointestinal dysfunction patients of Qi stagnation blood stasis syndrome: a
      clinical observation].
AB  - OBJECTIVE: To observe the effect and safety of plastering Chinese Compound
      Shenhuang Ointment (CSO) at Shenque (RN8) in promoting the rehabilitation of
      postoperative gastrointestinal dysfunction patients of qi stagnation blood stasis
      syndrome (QSBSS). METHODS: A prospective, multi-centered, randomized, double
      blinded, controlled trial was conducted in 220 postoperative gastrointestinal
      dysfunction patients of QSBSS. They were randomly assigned to two groups, the CSO
      group (110 cases) and the placebo group (110 cases). CSO was plastered at Shenque
      (RN8) for 5 days after operation. The time of exhaustion, defecation, the
      recovery of intestinal peristalsis, integrals of TCM syndrome, and serum levels
      of motilin (MOT)and somatostatin (SS) were observed. RESULTS: Compared with the
      placebo group, the condition of exhaustion and defecation, the recovery of
      intestinal peristalsis on the 3rd day after operation was all improved (P <
      0.05). The integrals of TCM syndrome at day 2, 3, and 4 were more significantly
      lowered in the CSO group than in the placebo group (P < 0.01, P < 0.05). The
      total effective rate of TCM syndrome was 95.3% in the CSO group, better than that
      in the placebo group (91.8%, P < 0.05). Compared with the placebo group, the
      serum MOT level increased and the serum SS level decreased at day 5 after
      operation in the CSO group (P < 0.05). CONCLUSIONS: The plastering of CSO at
      Shenque (RN8) could advance the time of exhaustion and defecation, and improve
      patients' clinical symptoms. And patients could tolerate well.

PMID- 25046946
TI  - [Treatment of HBeAg positive chronic hepatitis B by xiaoyao powder combined with
      interferon-alpha: a clinical observation].
AB  - OBJECTIVE: To study the efficacy of Xiaoyao Powder (XYP) combined with interferon
      alpha (IFN-alpha) in treating HBeAg positive chronic hepatitis B (CHB) patients
      and the effect on their quality of life (QOL). METHODS: Totally 193 patients with
      HBeAg-positive CHB confirmed by liver biopsy were randomly assigned to 2 groups,
      Group A (94 cases) and Group B (99 cases). IFN-alpha1b was subcutaneously
      injected to patients in Group A at the dose of 50 microg, thrice per week. Those
      in Group B additionally took XYP. The therapeutic course for all was 24 weeks.
      Clinical efficacy was observed by assessing ALT restoration rate, HBeAg negative
      rate, HBeAg conversion rate, HBV DNA negative rate, complete response rate,
      partial response rate, and symptoms integral. The evaluation of QOL was performed
      by using chronic liver disease questionnaire (CLDQ) score. Adverse reaction
      occurrence rate was observed in the two groups. RESULTS: Better effects were
      obtained in Group A on ALT restoration rate, HBeAg negative rate, HBV DNA
      negative rate, complete response rate, partial response rate, TCM symptoms
      integral, the total effective rate of TCM sysmptoms, CLDQ score, and adverse
      reaction rates, showing statistical difference when compared with Group B (P <
      0.05, P < 0.01). CONCLUSION: XYP could elevate the efficacy of TCM symptoms of
      HBeAg-positive CHB patients and anti-viral effect, improve their QOL, and reduce
      adverse reaction of IFN-alpha.

PMID- 25046947
TI  - [Effectiveness of integrative medicine for preventing postoperative recurrence of
      primary hepatic carcinomas: a systematic review].
AB  - OBJECTIVE: To systematically evaluate the effectiveness of integrative medicine
      (IM) for preventing postoperative recurrence of primary hepatic carcinomas (PHC).
      METHODS: Such databases as The Cochrane Library, PubMed, EMbase, China National
      Knowledge Infrastructure (CNKI), VIP Database, Wan-fang Database were retrieved
      to collect randomized controlled trials (RCTs) on preventing postoperative
      recurrence of PHC by IM. The retrieval period started from database establishment
      to June 2013. Literature screening, data extraction, and quality evaluation were
      performed by two reviewers strictly according to inclusion criteria. Meta
      analysis was conducted using RevMan 5.2 Software. RESULTS: A total of 5 RCTs
      involving 367 patient cases were included. Results of Meta-analysis showed that
      the IM group was superior to the Western medicine (WM) group in the 1-, 2-, and 3
      year recurrence rates (P < 0.05). CONCLUSION: In the prevention of postoperative
      recurrence of PHC, the effectiveness of IM was more significant, when compared
      with treatment of Western medicine.

PMID- 25046948
TI  - [Wuling capsule played an assistant role in primary prevention of post-stroke
      depression: a clinical research].
AB  - OBJECTIVE: To observe the primary prevention role of Wuling Capsule (WC) on
      poststroke depression (PSD) patients. METHODS: Acute stroke patients were
      recruited and randomized into 2 groups by stratification, 55 in each group. All
      patients received same routine treatment of cardiovascular diseases. Patients in
      the experimental group additionally took WC (0.33 g each pill), 3 pills per day,
      three times per day; while those in the control group additionally took placebos,
      3 pills per day, three times per day. Two weeks consisted of one therapeutic
      course. The diagnosis of PSD was performed once every other week. Those in
      accordance with PSD diagnosis discontinued any drug therapy. Those not in
      accordance with PSD diagnosis continued the drug therapy for 1-12 therapeutic
      course(s) (in total of 6 months). If they were still not in accordance with PSD
      diagnosis, then they discontinued the drug therapy. The morbidity of PSD, the
      average time of depression occurrence, Hamilton depression rating scale (HAMD)
      score, and adverse reactions were observed. RESULTS: The 1-, 3-, and 6-month
      morbidity of PSD was 8%, 16%, and 34% in the experimental group, while they were
      19.6%, 29.4%, and 54.9% in the control group. The occurrence rate was lower in
      the experimental group than in the control group. Besides, there was statistical
      difference in the 6-month occurrence rate between the two groups (chi2 = 4.465, P
      < 0.05). The average time of PSD occurrence was longer in the experimental group
      than in the control group (14.96 +/- 8.31 weeks vs. 9.36 +/- 6.06 weeks; t=6.762,
      P < 0.05). The HAMD score at the PSD occurrence was 11.96 +/- 2.14 in the
      experimental group, lower than that of the control group (14.57 +/- 4.24),
      showing statistical difference (t=5.641, P < 0.05). CONCLUSION: WC was superior
      to the placebos in lowering the incidence of PSD, delaying the occurrence time of
      PSD, attenuating the depression degree of PSD, and had certain preventive effect
      on the incidence of PSD.

PMID- 25046949
TI  - [Effect of yiqi huaju recipe combined with routine therapy in treating
      hypertension patients with metabolic syndrome: a clinical study].
AB  - OBJECTIVE: To investigate the therapeutic effect of Yiqi Huaju Recipe (YHR)
      combined with routine therapy on the blood pressure, the blood pressure
      variability and other cardiovascular risk factors in hypertension patients
      complicated with metabolic syndrome (MetS). METHODS: Totally 43 hypertension
      patients complicated with MetS were recruited in this study and randomly assigned
      to the treatment group (22 cases, treated with basic routine treatment +YHR) and
      the control group (21 cases, treated with basic routine treatment + placebo). The
      treatment course was 12 weeks. Detected were parameters such as 24-h ambulatory
      blood pressure monitoring (ABPM), body mass index (BMI), waist circumference
      (WC), waist to hip ratio (WHR), homeostatic model assessment for insulin
      resistance (HOMA-IR), fasting glycosylated hemoglobin A1c (HbA1c), fasting plasma
      glucose (FPG), 2 h postprandial plasma glucose (2 h PPG), fasting plasma insulin
      (FPI), serum lipid, etc. RESULTS: The anthropometric parameters and plasma
      glucose levels (except HbAlc) were obviously lowered after treatment than before
      treatment in the treatment group (P < 0.01, P < 0.05). Besides, better effects
      were obtained in the WC, WHR, 2 h PPG, FPI and HOMA-IR (P < 0.05). The average
      blood pressure amplitude, the blood pressure variability, and blood pressure load
      at any time point were more obviously improved in the two groups after treatment
      than before treatment (P < 0.01, P < 0.05). Besides, partial indices were better
      in the treatment group than in the control group (P < 0.01, P < 0.05).
      CONCLUSIONS: YHR combined with routine therapy exhibited better effect on
      reducing the blood pressure amplitude, the blood pressure variability, and the
      blood pressure load in hypertension patients complicated with MetS. It could also
      effectively decrease the risk of other vascular disease.

PMID- 25046950
TI  - [Treatment of declining in ovarian reserve by shen-reinforcing and menstrual
      cycle-regulating therapy combined with western medicine: a clinical observation].
AB  - OBJECTIVE: To observe the clinical effect of Shen-reinforcing and menstrual cycle
      regulating therapy (SRMCRT) combined with Western medicine (WM) in treating
      decline in ovarian reserve (DOR). METHODS: Totally 78 patients with DOR were
      assigned to the traditional Chinese medicine combined WM group (abbreviated as IM
      group, 40 cases), and the WM group (38 cases) according to random digit table
      method. Patients in the WM group were treated with hormone replacement therapy,
      while those in the IM group additionally received SRMCRT. The therapeutic course
      for all was 3 consecutive months. The therapeutic efficacy was compared between
      the two groups. The serum levels of follicle stimulating hormone (FSH),
      FSH/luteinizing hormone (LH), and estradiol (E2), as well as the development of
      sinus follicles were compared between before and after treatment in the two
      groups. RESULTS: The therapeutic effective rate was 92.5% in the IM group, higher
      than that of the WM group (73.68%, P < 0.05). The serum levels of FSH, FSH/LH,
      and E2 decreased (P < 0.05) and the number of the sinus follicle increased (P <
      0.05) in the two groups after treatment. Besides, IM was superior in decreasing
      serum levels of FSH and FSH/LH, and increasing the number of the sinus follicle
      (P < 0.05). CONCLUSIONS: SRMCRT was an effective method for treating ROD. IM was
      superior in decreasing serum levels of FSH and FSH/LH, and increasing the number
      of the sinus follicle.

PMID- 25046951
TI  - [A literature review on Chinese medicine syndrome and syndrome elements of
      chronic fatigue syndrome].
AB  - OBJECTIVE: To research the distribution characteristics of Chinese medicine (CM)
      syndrome and syndrome elements of chronic fatigue syndrome (CFS) by analyzing
      literature in recent 20 years. METHODS: Relevant literature on treating CFS by
      syndrome differentiation of CM at home were retrieved by computer and manual
      ways. Database were established by using EpiData 3.1 to conduct frequency
      analysis of syndrome and syndrome elements. RESULTS: The most common clinical
      syndromes were Xin-Pi deficiency syndrome, Gan stagnation Pi deficiency syndrome,
      Gan-Shen yin deficiency syndrome, Gan qi stagnation syndrome, and Pi-Wei qi
      deficiency syndrome. Disease locations were sequenced as Pi, Gan, Shen, and Xin.
      The clinical pathogenesis of CFS was characterized by deficiency of vital energy,
      complicated with intermingled excess and deficiency. Asthenia of healthy energy
      was mainly manifested as qi deficiency, blood deficiency, and yin deficiency,
      while excess of sthenia was mainly manifested as qi stagnation, phlegm dampness,
      and static blood. CONCLUSIONS: Research of CM syndrome starting from syndrome
      elements can better unify and standardize clinical syndrome differentiation.
      Results of literature analysis can provide reference for further studies.

PMID- 25046952
TI  - [Effect of chaishu sijun decoction on the gonad axis of gan-qi stagnation, Pi
      deficiency, and gan-qi stagnation pi deficiency model rats].
AB  - OBJECTIVE: To observe changes of gonad functions of Gan-qi stagnation (GS), Pi
      deficiency (PD), Gan-qi stagnation Pi deficiency (GSPD) model rats, and the
      effect of Chaishu Sijun Decoction (CSD) on them. METHODS: Rats were randomly
      divided into 7 groups according to romdom digit table, i.e., the normal control
      group, the GS model group, the GS medication group, the PD model group, the PD
      medication group, the GSPD model group,and the GSPD medication group, 10 in each
      group. Rats in the GS model group, the PD model group, and the GSPD model group
      were treated with chronic restraint, improper diet +excessive fatigue, chronic
      restraint +improper diet +excessive fatigue. The model was established for 4
      successive weeks. Starting from the 15th day of modeling, CSD at the daily dose
      of 3.57 g/kg was given by gastrogavage to them for 14 successive days. Equal
      volume of distilled water was given by gastrogavage to rats in each model group
      and the normal control group for 14 successive days. The blood contents of
      gonadotrophin releasing hormone (GnRH), follicular stimulating hormone (FSH),
      luteinizing hormone (LH), estradiol (E2), and testosterone (T) were detected in
      rats of each group. RESULTS: Compared with the normal control group, there was
      statistical difference in GnRH, T, E,, and FSH in the GS, PD, and GSPD model
      groups (P < 0.05, P < 0.01). The content of LH was elevated in the GS model group
      (P < 0.05) and declined in the GSPD model group (P < 0.01). Compared with the GS
      model group, the contents of FSH, LH, and T decreased and E2 increased in the PD
      model group (all P < 0.05); the contents of FSH and LH also declined in the GSPD
      model group (P < 0.05). Compared with the PD model group, the T content increased
      and FSH decreased in the GSPD model group (all P < 0.05). Compared with each
      corresponding model group, the FSH content decreased (P < 0.01) and LH increased
      in the GS medication group; the T content increased, E2 and LH decreased (P <
      0.05, P < 0.01) in the PD medication group; the T content decreased (P < 0.01),
      GnRH, E2, FSH, and LH increased (P < 0. 05, P < 0.01) in the GSPD medication
      group. CONCLUSIONS: There exist different degrees of abnormal function of the
      gonad axis in the GS, PD, and GSPD models. CSD had certain regulatory effect on
      the 3 syndromes. Of them, it showed a more comprehensive role in improving the
      gonad function axis. Results of this experiment had provided the experimental
      evidence for higher correlation between CSD and GSPD syndrome.

PMID- 25046953
TI  - [Protection and bidirectional effect of rhubarb anthraquinone and tannins for
      rats' liver].
AB  - OBJECTIVE: To compare the bidirectional effect of rhubarb total anthraquinone
      (TA) and total tannins (TT) on rats' liver. METHODS: One hundred rats were
      randomly divided into 10 groups, i.e., the blank group, the model group, the
      blank + high dose TA group, the blank +low dose TA group, the blank + high dose
      TT group, the blank + low dose TT group, the model + high dose TA group, the
      model + low dose TA group, the model +high dose TT group, and the model + low
      dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to
      prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude
      drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats
      in all groups except the blank group and the model group, once daily for 6
      successive days.The general state of rats, biochemical indices such as alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
      (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF
      beta1), as well pathological results of rat liver tissues. Finally the protection
      laws of TA and TT for rats' liver were analyzed using factor analysis. RESULTS:
      Compared with the blank control group, all biochemical indices increased in the
      blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA
      group; AST, ALT, and HA also increased in the blank +high dose TT group (P <
      0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1
      significantly decreased in the model + low dose TA group, the model + high dose
      TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and
      ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01).
      Pathological results showed that mild swollen liver cells in the model + high
      dose TA group. Fatty degeneration and fragmental necrosis around the central
      veins occurred in the blank + high dose TA group. The pathological injury was
      inproved in the model +low dose TA group. Two common factors, liver fibrosis and
      liver cell injury, were extracted by using factor analysis. TA showed stronger
      improvement of the two common factors than TT. CONCLUSIONS: Rhubarb TA and TT
      showed protective and harmful effects on rats' liver. At an equivalent dosage, TA
      had better liver protection than TT. High dose TT played a role in liver injury
      to some extent.

PMID- 25046954
TI  - [Effect of Sijunzi decoction on the proliferation of side population cells of
      human gastric cancer cell line].
AB  - OBJECTIVE: To observe the proliferation changes of the side population of gastric
      cancer cell line SGC-7901 cells (SP), the non-side population (NSP) cells, and
      unsorted cells (Total) after intervened by Sijunzi Decoction (SD) containing
      serum. METHODS: Sixteen pure bred New Zealand rabbits were equally divided into
      the normal control group, the low dose SD group (at the daily dose of 7 mL/kg),
      the middle dose SD group (at the daily dose of 14 mL/kg), and the high dose SD
      group (at the daily dose of 28 mL/kg) according to the random digit table.
      Rabbits' serum was extracted after equal volume of corresponding medication was
      given by gastrogavage twice daily for 2 consecutive weeks. The drug serum was
      identified using high performance liquid chromatography. SP cells of SGC-7901
      were detected using flow cytometry, SP and NSP cells were screened. The
      proliferation curve of SP, NSP, and Total cells were detected with CCK-8 assay.
      Changes of their proliferation were also observed. RESULTS: Ginsenoside Rg1, an
      effective ingredient in SD was detected in prepared drug serum. The proliferation
      of SGC-7901 SP cells was significantly higher than that of NSP cells and Total
      cells (P < 0.05). Drug serum on gastric cancer cell line SGC-7901 SP, NSP, and
      Total cells could inhibit their proliferation, but its inhibition on SP cells'
      proliferation was significantly lower than on NSP and Total cells (P < 0.05).
      CONCLUSIONS: SD could significantly inhibit the proliferation of gastric cancer
      cell line SGC-7901 SP, NSP, and Total cells. But there exist obvious difference
      in the inhibition among the three groups.

PMID- 25046955
TI  - [Berberine inhibited apoptosis of human umbilical vein endothelial cells induced
      by Staphylocoocus aureus: an experimental research].
AB  - OBJECTIVE: To study the inhibition of berberine (BBR) against ECV-304 apoptosis
      induced by Staphylococcus aureus (S. aureus). METHODS: ECV-304 cells were pre
      treated with 128 microg/mL BBR for 2 h and then S. aureus was added (1:100). The
      viability of cells was detected by MTT (3-4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay. The morphological changes were observed by
      Hoechst 33258 staining. The protection of BBR for infected cells was detected by
      DNA Ladder. RESULTS: ECV-304 cells' viability were not obviously affected by
      berberine. But S. aureus induced ECV-304 cells' viability could be significantly
      inhibited by pre-treatment of BBR (P < 0.05). Besides S. aureus-induced ECV-304
      apoptosis could be reduced, with significantly lessened apoptotic body and
      unobvious DNA degradation. CONCLUSION: BBR could significantly inhibit S. aureus
      induced ECV-304 apoptosis.

PMID- 25046956
TI  - [Effect of Chinese herbs for stasis removing and collaterals dredging upon
      angiotensin-converting enzyme 2-angiotensin-(1-7)-mas axis in the renal cortex of
      diabetic nephropathy rats].
AB  - OBJECTIVE: To observe the effect of Chinese herbs for stasis removing and
      collaterals dredging (CHSRCD) upon angiotensin-converting enzyme 2-angiotensin-(1
      7)-Mas axis in the renal cortex of diabetic nephropathy rats. METHODS: Totally 89
      male Sprague-Dawley rats were randomly divided into the blank control group (C
      group, n=22), the high-glucose high-fat control group (H group, n=10), and the
      streptozotocin (STZ)-injecting group (n=57). The diabetes rat model (n=50) was
      induced by feeding high-glucose high-fat diet in combination with intraperitoneal
      injection of STZ, which were further divided into the model group (M group,
      n=24), the irbesartan group (I group, n=13), and the CHSRCD (Z group, n=13). Rats
      in I and Z groups were intragastrically fed with suspension of irbesartan and
      CHSRCD, once daily for 16 weeks. Equal volume of drinking water was administrated
      to rats in the rest groups. Blood glucose and 24 h urine protein quantitation
      were tested at four time points. And the mRNA expression of ACE2 and Mas at
      various time points was detected by Real-time PCR, immunohistochemical assay, and
      Western blot. Quantitative analyses of ACE2 and Mas protein expression were
      performed at the end of week 16. RESULTS: Compared with the C group, blood
      glucose increased in the H and M groups (P < 0.01). It was higher in the H group
      (P < 0. 01). 24 h urine protein quantitation at different time points increased
      in the M group, and it was higher than that in the H group (P < 0.05). Compared
      with the M group, 24 h urine protein quantitation decreased at the end of week 8
      in the I group, and at the end of week 8 and 16 in the Z group (P < 0.05). It was
      lower in the Z group than in the I group at the end of week 16 (P < 0.05).
      Compared with the C and H groups, the expression of ACE2 mRNA in the renal cortex
      was lower in the M group at the end of week 16 (P < 0.01). Compared with the M
      group, it was higher in the Z group (P < 0. 01). There was no statistical
      difference in the expressions of Mas mRNA at the end of week 16 between the C
      group and the M group (P > 0.05). It was lower in the M group than in the H group
      (P < 0.05). It was higher in the Z group than in the M group (P < 0.05), and
      higher than in the I group (P < 0.05). The expression of ACE2 and Mas protein in
      the M group decreased as time went by. The expression quantitation of ACE2 and
      Mas protein at the end of week 16 was lower in the M group than in the C group (P
      < 0.05). Compared with the M group, ACE2 expression of the Z group and Mas of the
      I and Z groups increased more significantly (P < 0. 05). CONCLUSION: CHSRCD could
      play a role in renal protection for diabetic nephropathy rats by up-regulating
      the mRNA and protein expression of ACE2 and Mas, promoting the ACE2-Ang-(1-7)-Mas
      axis, and lowering urinary protein.

PMID- 25046957
TI  - [Effect of compound qingqin liquid on the expression of toll-like receptor in the
      renal tissue of rats with urate nephropathy].
AB  - OBJECTIVE: To investigate the effect of compound qingqin liquid (CQL) on Toll
      like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) in rats with urate
      nephropathy, and to explore its renal protection mechanism. METHODS: Totally 55
      SD rats were randomly divided into 5 groups, i.e., the normal control group (n
      =5), the model group (n =10), the positive drug group (n=10), and the high-,
      medium-, low-dose CQL groups (n=10) respectively. The urate nephropathy model was
      induced by intragastrically administering adenine and feeding yeast. Distilled
      water was intragastrically administered at the daily dose of 10 mL/kg to rats in
      the normal control group and the model group. Allopurinol was intragastrically
      administered at the daily dose of 9.33 mg/kg to rats in the positive control
      group. CQL was intragastrically administered at the daily dose of 3.77, 1.89,
      0.94 g/kg to rats in the high-, medium-, and low-dose CQL groups. Rats of each
      group were executed in batches at the 4th and 6th week respectively. Their kidney
      tissues were taken out to determine the mRNA transcription level of TLR2 and TLR4
      by reverse transcription-polymerase chain reaction (RT-PCR). The protein
      expression level of TLR2 and TLR4 were determined by Western blot. The protein
      expression level of TLR4 was also detected by immunohistochemical assay. RESULTS:
      At week 4 and 6, the protein expression of TLR2 and TLR4 as well as the mRNA
      transcription of TLR4 increased in the model group, when compared with the
      control group (P < 0.05, P < 0.01). Compared with the model group, there was no
      statistical difference in the transcription level of TLR2 mRNA or TLR4 mRNA among
      the 3 CQL groups (P > 0.05) at week 4 and 6. Additionally, at week 6, the protein
      expression of TLR4 and TLR2 could be reduced by CQL (P < 0.05, P < 0.01).
      CONCLUSION: CQL might protect kidney tissue against inflammatory injury by
      inhibiting the protein expression levels of TLR2 and TLR4.

PMID- 25046958
TI  - [Effect of compound bushen recipe on chronic fatigue syndrome in C. elegans: an
      experimental study].
AB  - OBJECTIVE: To evaluate the effect of compound bushen recipe (CBR) in improving
      the survival state of stress and the overall life span in C. elegans by
      simulating chronic fatigue syndrome (CFS) under various stress states. METHODS:
      The tolerance and the average survival time of adult larvae against heat stress
      (35 degrees C), oxidative stress (250 microg/mL juglone), and in vivo Abeta
      protein toxicity (Abeta(1-42) transgenic mutant CL4176) under the intervention of
      the high (500 mg/L), middle (250 mg/L), and low (100 mg/L) dose CBR were
      observed. The effect of CBR on the average live time (at 25 degrees C), movement
      distance in 20 seconds, the frequency of pharyngeal pump in 30 seconds, and the
      reproductive capability were assessed. RESULTS: Compared with the control group,
      the survival time of heat stressed C. elegans could be significantly increased in
      each CBR group (P < 0.01). The survival time of heat stressed C. elegans could be
      elongated, the protein toxicity be attenuated, and the live time prolonged in the
      high and middle dose CBR groups (P < 0.01, P < 0.05).The movement distance and
      the frequency of pharyngeal pump could also be increased in the high dose CBR
      group (P < 0.01). There was no statistical difference in the reproductive
      capability among all groups (P > 0.05). CONCLUSIONS: CBR could significantly
      enhance the stress capacity of C. elegans against internal and external
      environment, and prolong their lifespan. It did not interfere their normal
      production, and also could improve the quality of life, thus laying a foundation
      for further mechanism studies and pharmacological researches on CBR in preventing
      and treating CFS.

PMID- 25046959
TI  - [Effect and mechanism of jianpi qinghua recipe on renal functions of adriamycin
      induced nephropathic rats from the angle of inhibiting renal fibrosis].
AB  - OBJECTIVE: To explore the effect of Jianpi Qinghua Recipe (JQR) on renal
      functions of adriamycin-induced focal segmental glomerular sclerosis (FSGS) rats
      from the angle of activating fibroblasts to myofibroblast (MyoF). METHODS:
      Totally 56 rats were randomly divided into the normal control group (n=8), the
      sham-operation group (n =8), and the model group (n=40). The FSGS rat model was
      induced by nephrectomy of left kidney plus intravenous injection of adriamycin.
      Successfully modeled rats were further divided into 5 groups, i.e., the model
      group, the JQR group, the JPR (Jianpi Recipe) group, the QHR (Qinghua Recipe)
      group, and the NDQ (Niaoduqing) group, 8 in each group. Corresponding drugs were
      administered to rats in all groups, 2 mL each time, for 56 days. The effect of
      JQR on serum creatinine (SCr), urea nitrogen, 24-h urinary protein excretion, a
      smooth muscle actin (alpha-SMA) mRNA, collagen type III (Col III) mRNA,
      fibronectin (FN) mRNA, and collagen type IV (Col IV) mRNA were observed. RESULTS:
      JQR could significantly lower SCr, urea nitrogen, and 24-h urinary protein
      excretion levels (P < 0.01), and significantly decrease mRNA levels of alpha-SMA,
      Col III, FN, and Col IV (P < 0.01). It was advantageous over the NDQ group.
      Compared with JPR, the relative expression levels of Col III mRNA and FN mRNA of
      JQR and QHR were significantly lower (P < 0.01). CONCLUSIONS: JQR could improve
      the renal function and renal fibrosis in the adriamycin-induced nephropathic
      model rats. Its efficacy was superior to that of NDQ. Its mechanisms might be
      linked with inhibiting activation of fibroblasts.

PMID- 25046960
TI  - [Changing laws of serum high mobility group box 1 protein in septic rats and the
      intervention effect of xuebijing].
AB  - OBJECTIVE: To investigate the changing laws of serum high mobility group box 1
      protein (HMGB1) in septic rats and intervention effect of Xuebijing on it.
      METHODS: Lipopolysaccharide (LPS) (5 mg/kg BW) was intravenously injected into
      the tail vein of healthy male Wistar rats to prepare the sepsis rat model. In
      Experiment 1: 50 Wistar rats were randomly divided into three groups, i.e., the
      normal group (A, n=10); the LPS model group (B, n=10), the LPS +Xuebijing
      treatment group (C, n=30). Rats in the C group were further divided into three
      subgroups, i.e., 2 h before LPS injection (group C1), 2 h after LPS injection
      (group C2), and 8 h after LPS injection (group C3), 10 in each group. Blood
      samples were collected from the caudal vein to detect serum HMGB1 levels by
      Western blot at 4, 12, 24, 48, and 72 h after LPS injection. Experiment 2: 30
      Wistar rats were equally divided into the LPS model group (D) and the LPS +
      Xuebijing treatment group (E), 15 in each group. They were treated as rats in the
      B group and the C1 group respectively. Five rats were sacrificed at 12, 24, and
      48 h after LPS injection in the two groups. Blood as well as the tissue samples
      were harvested to measure such indices as ALT, AST, Cr, and BUN, as well as
      pathological changes of liver, lung, and kidney. RESULTS: (1) Compared with the A
      group, serum HMGB1 levels were higher at various time points in the B group (P <
      0.05). Compared with the B group, serum HMGB1 levels at 12,24,48, and 72 h
      decreased in the C1, C2, and C3 groups. Besides, the decrease was more obvious at
      24 h and 48 h.The decrement in the C3 group was less than that in the C1 and C2
      groups (P < 0.05). (2) In the D group, ALT, AST, Cr, and BUN were significantly
      higher than those in the A group and reached the peak at 24 h (P < 0.05).
      Compared with the E group, AST, Cr, and BUN at 24 and 48 h, and ALT at each time
      point decreased significantly in the E group (P < 0.05). (3)The results of
      pathological section of liver, lung, and kidney showed local congestion and
      hemorrhage, cell edema/necrosis/degeneration, infiltration of inflammatory cells,
      damage of characteristic structures and so on; particularly serious lesion
      occurred at 24 and 48 h in the D group. The microscopic lesion was obviously
      alleviated in the E group than in the D group at corresponding time points.
      CONCLUSIONS: The serum HMGB1 levels increased in septic rats, with late
      occurrence of peak value and longer duration of the high value. HMGB1 played an
      important role in excessive inflammatory response and multiple organ dysfunction.
      Xuebijing could reduce the serum levels of HMGB1, improve biochemical parameters,
      and attenuate severe inflammatory response of liver, lung, and kidney tissues in
      septic rats. Besides, the earlier use, the better effect obtained.

PMID- 25046961
TI  - [Effect of Lignum sappan containing serum on the proliferation cycle of human
      lung cancer cell line PG: a comparative study].
AB  - OBJECTIVE: To explore the effect of Lignum Sappan (LS) containing serum on the
      proliferation cycle arrest of human lung cancer cell line PG and its molecular
      mechanism. METHODS: The lung cancer PG cells were divided into four groups, i.e.,
      the blank control group, the LS group, the LS plus cisplatin group, and the
      cisplatin group. They were cultured by RPMI-1640 with 20% blank serum, RPMI-1640
      with 20% LS containing serum, RPMI-1640 with 20% LS containing serum plus 1
      microg/mL cisplatin, and RPMI-1640 with 20% blank serum plus 1 microg/mL
      cisplatin, respectively. The morphology of PG cells was observed using light
      microscope and laser scanning confocal microscope in each group. The cell cycle
      arrest was observed using flow cytometry. The expression of P16 and Rb1 mRNA was
      tested by PCR method. RESULTS: Under the light microscope and laser scanning
      confocal microscope, the apoptosis degree of PG cells in the LS group was
      significant, but less than that of the LS plus cisplatin group as well as the
      cisplatin group. Compared with the blank control group, the proportion of PG
      cells increased at G0/ G1 and S phases (P < 0.05) and decreased at G2/M phase (P
      < 0.01) in the LS group; The proportion of PG cells increased at G2/M and S
      phases (P < 0.05, P < 0.01) and decreased at G0/G1 phase (P < 0.01) in the LS
      plus cisplatin group as well as the cisplatin group. Compared with the LS group,
      the proportion of PG cells increased at G2/M and S phases (P < 0.05, P < 0.01)
      and decreased at G0/G1 phase (P < 0.01) in the LS plus cisplatin group as well as
      the cisplatin group. There was no statistical difference in PG cells at each
      phase between the cisplatin group and the LS plus cisplatin group (P > 0.05). The
      expression of P16 and Rb1 mRNA increased in the LS group, when compared with the
      blank control group. They also increased in the cisplatin group and the LS plus
      cisplatin group, higher than that of the LS group (P < 0.05). There was no
      statistical difference in the expression of P16 and Rb1 mRNA between the
      cisplatin group and the LS plus cisplatin group (P > 0.05). CONCLUSION: LS
      containing serum induced PG cell apoptosis by up-regulating the mRNA
      transcription levels of P16 and Rb1, thus resulting in PG cell arrest at G0/G1
      and S phases, which was different from the manner of cisplatin (achieved by
      arresting PG cells at G2/M and S phases through regulating cyclinB1 mRNA
      transcription).

PMID- 25046962
TI  - [Treatment of late stage liver cancer by Chinese herbs combined sunitinib in one
      case].

PMID- 25046963
TI  - [Study on English translation of CM pulse figure terminologies based on
      metaphor].

PMID- 25046964
TI  - [Research progress on clinician-reported dutcomes].

PMID- 25046965
TI  - Guest commentary. Innovation through collaboration in healthcare.

PMID- 25046966
TI  - Implementation of an innovative postoperative monitoring approach for patients
      with obstructive sleep apnea.
AB  - This article shares how William Osler Health System (Osler) achieved improved
      quality of care for clinically challenging patients using state-of-the-art
      technology combined with interprofessional and intermanagerial teamwork in an
      acute care setting. Obstructive sleep apnea, a respiratory disorder caused by
      upper airway obstruction, increases the risk of complications after anesthesia.
      Although an initial postoperative monitoring strategy designed for patients with
      obstructive sleep apnea at Osler ensured patient safety, it required
      reorganization to resolve operational challenges. Concerned stakeholders at all
      levels contributed to the development and implementation of a new program
      approach focused on remote pulse oximetry monitoring as a component of the
      standard of care. Osler has developed a case study to share its experience with
      other hospitals and health systems that are already engaged in or that are
      considering implementing such a program.

PMID- 25046967
TI  - Leveraging hospital formularies for improved prescribing.
AB  - Hospital formularies, guided by the Pharmacy and Therapeutics Committee, exist to
      optimize medication use by identifying and designating drugs of choice to guide
      rational prescribing, ultimately reducing patient risk and costs and improving
      patient outcomes. Guidelines and a framework exist to guide critical evaluations
      of medications for formulary listing; however, there may be opportunities to
      improve and standardize how a formulary change could be instituted in Canadian
      hospitals. A formulary change at an Ontario hospital revealed that there are some
      key challenges to the formulary change process including the importance of a
      robust project plan, appropriate resources, healthcare staff education, and
      acceptance.

PMID- 25046968
TI  - Improving patient access and streamlining processes through enterprise
      intelligence systems.
AB  - This article demonstrates how enterprise intelligence systems can be used to
      improve operational efficiency in hospitals. Enterprise intelligence systems mine
      raw data from disparate systems and transform the data into actionable
      information, which when used appropriately, support streamlined processes,
      optimize resources, and positively affect staff efficiency and the quality of
      patient care. Case studies on the implementation of McKesson Performance
      Visibility and Capacity Planner enterprise intelligence solutions at the
      Southlake Regional Health Centre and Lions Gate and Richmond Hospitals are
      provided.

PMID- 25046969
TI  - A framework for patient-centred care coordination.
AB  - Difficulty accessing patient information, duplication of effort, and breakdowns
      in communication within the medical infrastructure are some of the major issues
      challenging the quality of care and the efficiency of the Canadian healthcare
      system. In addition, patients are demanding faster access to the right services,
      improved outcomes, and more involvement in managing their own healthcare. This
      article presents a framework for patient-centred care that allows healthcare
      providers to deliver better and faster patient interventions with treatment plans
      based on a patient's complete medical history. RelayHealth provides the framework
      for patient-centred care coordination and fully integrates patient and provider
      interaction at all points on the healthcare continuum.

PMID- 25046970
TI  - The effect of late adoption of Canadian innovations: a case for implantable
      cardiac monitors.
AB  - Syncope is a sudden and generally momentary loss of consciousness, which can have
      serious adverse events. The outcomes of the syncope episode can vary from a fall
      to fatal accidents. Syncope has a major negative effect on the patient's health
      related quality of life. The economic burden of syncope on healthcare systems is
      considerable. There are no clear diagnostic pathways for identifying the cause of
      syncope; patients can be admitted to hospital and undergo expensive and often
      repeated and inconclusive diagnostic tests. Implantable cardiac monitors have
      been available for more than a decade to help early diagnosis of syncope in
      unexplained cases. However, despite being a Canadian invention, the use of the
      implantable cardiac monitors has been suboptimal in the Canadian healthcare
      system. This study provides an overview of syncope, its management, and presents
      the estimated potential cost savings per diagnosis of systematic use of
      implantable cardiac monitors in Ontario.

PMID- 25046971
TI  - Successful outsourcing: improving quality of life through integrated support
      services.
AB  - This article examines the way that non-clinical support services are provided in
      healthcare settings through outsourcing partnerships. The integrated support
      services model and benefits to patient experience and safety as well as
      organizational efficiency and effectiveness are explored through an examination
      of services at a busy urban community hospital.

PMID- 25046972
TI  - The power of engagement: creating the culture that gets your staff aligned and
      invested.
AB  - The Canadian government officially recognizes the value of staff engagement in
      providing better healthcare. Evidence demonstrates that engagement is connected
      to improved financial outcomes as well as better patient safety and clinical
      outcomes. There is a need for health leaders to create organizational cultures
      that simultaneously result in higher rates of employee and physician engagement,
      better clinical care, and lower costs. This article highlights the research and
      experience gained on the benefits of engagement, explores Studer Group's approach
      to improving both engagement and quality, and shares the results achieved by the
      firm's Canadian partners. In addition, it describes some of the "building blocks"
      that, together, create the necessary cultures of engagement inside organizations.

PMID- 25046973
TI  - Intramural hematoma and oozing rupture of left atrium after resection of wide
      based left atrial myxoma.
AB  - We describe a rare complication after the resection of the left atrial (LA)
      myxoma. After tumor resection, a large defect of the endocardium was reinforced
      with an autologous pericardial patch. Transesophageal echocardiography
      demonstrated a hematoma and pulsatile flow beneath the patch, without patch
      perforation or detachment. Bleeding increased after closure of the sternum.
      Intramural hematoma and oozing rupture of the LA were diagnosed. A small
      intramural vessel of the LA was identified as the main causative site of
      bleeding. The pericardial patch was repositioned with fibrin glue. Fibrin sheets
      and glue were applied for reinforcement of the LA from outside. 

PMID- 25046974
TI  - Reply to 'Preventing parastomal herniation in 2014 and beyond'.

PMID- 25046976
TI  - Activation of autophagic pathways is related to growth inhibition and senescence
      in cutaneous squamous cell carcinoma.
AB  - Cutaneous squamous cell carcinoma (SCC) is a very common resectable cancer;
      however, cutaneous SCC is highly resistant to chemotherapy if metastasis
      develops. Activating transcription factor 3 (ATF3) has been suggested as a marker
      of advanced or metastatic cutaneous SCC. Autophagy is one of the most important
      mechanisms in cancer biology and commonly induced by in vitro serum starvation.
      To investigate the role of autophagy activation in cutaneous SCC, we activated
      autophagic pathways by serum starvation in SCC13 and ATF3-overexpressing SCC13
      (ATF3-SCC13) cell lines. ATF3-SCC13 cells demonstrated high proliferative
      capacity and low p53 and autophagy levels in comparison with control SCC13 cells
      under basal conditions. Intriguingly, autophagic stimulation via serum starvation
      resulted in growth inhibition and senescence in both cells, while ATF3-SCC13
      cells further demonstrated growth inhibition and senescence. Apoptosis was not
      significantly induced by autophagy activation. Taken together, autophagy
      activation may be a promising antitumor approach for advanced cutaneous SCC. 

PMID- 25046975
TI  - Minichromosome Maintenance (MCM) Family as potential diagnostic and prognostic
      tumor markers for human gliomas.
AB  - BACKGROUND: Gliomas are the most common type of all central nervous system
      tumors. Almost all patients diagnosed with these tumors have a poor prognostic
      outcome. We aimed to identify novel glioma prognosis-associated candidate genes.
      METHODS: We applied WebArrayDB software to span platform integrate and analyze
      the microarray datasets. We focused on a subset of the significantly up-regulated
      genes, the minichromosome maintenance (MCM) family. We used frozen glioma samples
      to predict the relationship between the expression of MCMs and patients outcome
      by qPCR and western blot. RESULTS: We found that MCMs expression was
      significantly up-regulated in glioma samples. MCM2-7 and MCM10 expressions were
      associated with WHO tumor grade. High MCM2 mRNA expression appeared to be
      strongly associated with poor overall survival in patients with high grade
      glioma. Furthermore, we report that MCM7 is strongly correlated with patient
      outcome in patients with WHO grade II-IV tumor. MCM3 expression was found to be
      up-regulated in glioma and correlated with overall survival in patients with WHO
      grade III tumor. MCM2, MCM3 and MCM7 expression levels were of greater prognostic
      relevance than histological diagnosis according to the current WHO classification
      system. CONCLUSIONS: High expression of MCM 2, MCM3 and MCM7 mRNA correlated with
      poor outcome and may be clinically useful molecular prognostic markers in glioma.

PMID- 25046977
TI  - The effect of dental occlusal disturbances on the curvature of the vertebral
      spine in rats.
AB  - OBJECTIVE: To determine whether a unilateral increase or decrease in the bite
      affects the curvatures of the vertebral spine in rats. METHODS: 25 male Sprague
      Dawley rats were included. Five animals received no alteration on their bite.
      Bite was increased on 10 animals and molar teeth were extracted on 10 other
      animals. Frontal and lateral radiographs were taken on days 0, 7, 14 and 21.
      Distances from landmarks to a true vertical line were measured on both
      radiographs. RESULTS: Repeated measures analysis showed statistically significant
      differences between the amount of the curvature at the cervical and thoracic
      spines on frontal and lateral radiographs over time (P<0.05 and P<0.0001). One
      way ANOVA computed significant differences (P<0.05) at D14 at the cervical and
      thoracic spines on both, increased and decreased vertical dimension. CONCLUSION:
      Alterations in the dental occlusion affects the normal curvatures of the
      vertebral spine in rats.

PMID- 25046978
TI  - Evaluation of myelodysplasia syndrome screening during routine hematological
      analysis on the ADVIA 2120i.

PMID- 25046979
TI  - Ecological and social outcomes of a new protected area in Tanzania.
AB  - Balancing ecological and social outcomes of conservation actions is recognized in
      global conservation policy but is challenging in practice. Compensation to land
      owners or users for foregone assets has been proposed by economists as an
      efficient way to mitigate negative social impacts of human displacement from
      protected areas. Joint empirical assessments of the conservation and social
      impacts of protected area establishment involving compensation payments are
      scarce. We synthesized social and biological studies related to the establishment
      of the Derema forest corridor in Tanzania's biodiverse East Usambara Mountains.
      This lengthy conservation process involved the appropriation of approximately 960
      ha of native canopy agroforest and steep slopes for the corridor and monetary
      compensation to more than 1100 claimants in the surrounding villages. The
      overarching goals from the outset were to conserve ecological processes while
      doing no harm to the local communities. We evaluated whether these goals were
      achieved by analyzing 3 indicators of success: enhancement of forest
      connectivity, improvement of forest condition, and mitigation of negative impacts
      on local people's livelihoods. Indicators of forest connectivity and conditions
      were enhanced through reductions of forest loss and exotic species and increases
      in native species and canopy closure. Despite great efforts by national and
      international organizations, the intervention failed to mitigate livelihood
      losses especially among the poorest people. The Derema case illustrates the
      challenges of designing and implementing compensation schemes for conservation
      related displacement of people.

PMID- 25046980
TI  - The shelf life of farmed turbot (Scophthalmus maximus).
AB  - A total of 18 farmed turbot (Scophthalmus maximus) were slaughtered over 4
      successive weeks in November 2012 and stored in polystyrene boxes with ice until
      analyzed. The fish were stored between 1 and 22 d and presented to a taste panel
      and further analyzed for quality index method (QIM), microbiological analysis by
      real-time quantitative PCR (qPCR), taste, pH, color by computer imaging, protein
      denaturation with differential scanner calorimeter (DSC), texture hardness, and
      shear force. Results show small, but significant changes in physical and visual
      attributes such as texture and color. No gaping was observed. Only small changes
      in texture were observed explained by lack of myosin denaturation. The fillets
      became more white and yellow during storage, whereas the major changes occurred
      during the 1st week. A panel evaluating QIM and taste could not distinguish major
      differences in appearance and taste and over 15 d storage period, but were able
      to quantify the age by smell. Analysis of microorganisms on the epidermis
      displayed growth of Carnobacterium maltaromaticum, potentially inhibiting growth
      of other spoilage bacteria. Fish stored for 22 d were rejected by the taste panel
      caused by a stale smell and taste, but not bitter or rancid. It is concluded that
      turbot has a shelf life of at least 16 d. 

PMID- 25046981
TI  - Seizure detection with automated EEG analysis: a validation study focusing on
      periodic patterns.
AB  - OBJECTIVE: To evaluate an automated seizure detection (ASD) algorithm in EEGs
      with periodic and other challenging patterns. METHODS: Selected EEGs recorded in
      patients over 1year old were classified into four groups: A. Periodic lateralized
      epileptiform discharges (PLEDs) with intermixed electrical seizures. B. PLEDs
      without seizures. C. Electrical seizures and no PLEDs. D. No PLEDs or seizures.
      Recordings were analyzed by the Persyst P12 software, and compared to the raw
      EEG, interpreted by two experienced neurophysiologists; Positive percent
      agreement (PPA) and false-positive rates/hour (FPR) were calculated. RESULTS: We
      assessed 98 recordings (Group A=21 patients; B=29, C=17, D=31). Total duration
      was 82.7h (median: 1h); containing 268 seizures. The software detected 204
      (=76.1%) seizures; all ictal events were captured in 29/38 (76.3%) patients; in
      only in 3 (7.7%) no seizures were detected. Median PPA was 100% (range 0-100;
      interquartile range 50-100), and the median FPR 0/h (range 0-75.8; interquartile
      range 0-4.5); however, lower performances were seen in the groups containing
      periodic discharges. CONCLUSION: This analysis provides data regarding the yield
      of the ASD in a particularly difficult subset of EEG recordings, showing that
      periodic discharges may bias the results. SIGNIFICANCE: Ongoing refinements in
      this technique might enhance its utility and lead to a more extensive
      application.

PMID- 25046982
TI  - Ictal ontogeny in Dravet syndrome.
AB  - OBJECTIVE: To define seizure characteristics of Dravet syndrome (DS) with video
      electroencephalographic (EEG) recording in different age groups. METHODS: We
      reviewed 23 patients with 63 seizures in different age groups: group 1 (0-5years
      old); group 2 (6-10years old); and group 3 (11 or above). RESULTS: We included 7,
      11 and 5 patients in groups 1, 2, and 3 respectively. Younger children had
      seizures while awake (p=0.005), provoked seizures (p=0.05), focal seizure
      semiology (p=0.02) and long seizure duration (p=0.0004). Older children had
      seizures from sleep (p=0.004), generalized seizure semiology (p=0.01) and short
      seizure duration (p=0.0007). A generalized ictal discharge was the most commonly
      observed EEG pattern (15/23, 65%), more frequently found in older children
      (p=0.01). Ten patients (43%) had unclassified seizures or seizures with
      discordant EEG results. Postictal EEG suppression was found in 9 (39%).
      CONCLUSION: The phenotype of seizures and ictal EEG patterns in DS vary with age.
      SIGNIFICANCE: These findings will enhance the recognition of DS in the adolescent
      population. The incidence of postictal EEG suppression seen in DS is significant
      because it is a possible biomarker for sudden unexpected death in epilepsy.

PMID- 25046983
TI  - Distribution of anionic and nonionic surfactants in a sewage-impacted
      Mediterranean coastal lagoon: inputs and seasonal variations.
AB  - In this work we have monitored the seasonal inputs, occurrence and distribution
      of the world's most widely used surfactants (linear alkylbenzene sulfonates, LAS,
      nonylphenol polyethoxylates, NPEOs, and alcohol polyethoxylates, AEOs) in Mar
      Menor lagoon (SE Spain) and its main tributary (El Albujon) for the first time.
      Concentration of target compounds was determined in both surface waters and
      sediments after solid phase extraction and pressurized liquid extraction,
      respectively, followed by liquid chromatography-mass spectrometry (LC-MS). There
      were significant differences in surfactant fluxes from El Albujon towards Mar
      Menor depending on the season and the day of the week, with maximum estimated
      annual inputs being detected for LAS (406 kg) and their metabolites, sulfophenyl
      carboxylic acids (482 kg). Average concentrations of surfactants in the lagoon
      were between 44 and 1665 MUg/kg in sediment, and between 0.3 and 63 MUg/L in
      water. These levels were significantly higher for samples collected near the
      shore than for those measured inside the lagoon itself. Overall, the occurrence
      and distribution of surfactants in the system could be explained due to a
      combination of different sources (surface and groundwater inputs, treated and
      untreated wastewater effluents, towns, ports, etc.) and simultaneous in-situ
      physicochemical and biological processes, with an special emphasis on degradation
      during warmer months.

PMID- 25046985
TI  - Photodynamic therapy in Argentina.
AB  - The use of endogenous Protoporphyrin IX generated through the heme biosynthetic
      pathway after administration of 5-aminolevulinic acid (ALA) has led to many
      applications in photodynamic therapy (PDT). In Buenos Aires, Argentina, the
      Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), reported for the
      first time, in 1975, porphyrin synthesis from ALA in highly dividing plant
      tissues. Increased porphyrin synthesis in tumours as well as cell
      photosensitisation was reported soon after. Our group is also interested in
      studying the use of new synthetic lipophilic derivatives of ALA as well as ALA
      delivery in liposomes. We have elucidated the mechanism of ALA transport in
      mammalian and yeast cells. The interactions between ALA-PDT and nitric oxide were
      investigated in three murine adenocarcinoma cell lines. In the National
      University of Rio Cuarto, Cordoba, a group is devoted to the synthesis of new
      porphyrin-derived photosensitisers to study their effects on photoinactivation of
      bacterial and mammalian cells death by PDT. At the Centre of Electron Microscopy
      of the Cordoba National University, a prototype of a 630nm noncoherent light
      source was designed and constructed. Cost of the light source and scarce
      knowledge of the benefits of PDT by physicians limit the spread of the treatment
      throughout the country. 

PMID- 25046984
TI  - Assessment of sediment ecotoxicological status as a complementary tool for the
      evaluation of surface water quality: the Ebro river basin case study.
AB  - According to the European Water Framework Directive (WFD), assessment of surface
      water status is based on ecological and chemical status that is not always in
      coherence. In these situations, ecotoxicity tests could help to obtain a better
      characterization of the ecosystems. The general aim of this work is to design a
      methodology to study the ecotoxicological status of freshwater systems. This
      could be useful and complementary to ecological status, for a better ecological
      characterization of freshwater systems. For this purpose, sediments from thirteen
      sampling sites within the Ebro river watershed (NE Spain) were collected for
      ecotoxicity characterization. The ecotoxicity of pore water has been evaluated
      employing the test organisms Vibrio fischeri, Pseudokirschneriella subcapitata
      and Daphnia magna, while whole sediment ecotoxicity was evaluated using Vibrio
      fischeri, Daphnia magna, Nitzschia palea and Chironomus riparius. An analysis of
      acid-volatile sulfide (AVS) and simultaneously extracted metals (SEM) was
      performed to evaluate the sediment toxicity associated to bioavailable metals.
      Moreover, data about priority pollutants defined by the WFD in water, sediment
      and fish as well as data of surface water status of each sampling point were
      provided by the Monitoring and Control Program of the Ebro Water bodies. In
      general terms, whole sediment bioassays have shown more toxicity than pore water
      tests. Among the different organisms used, P. subcapitata and C. riparius were
      the most sensitive in pore water and whole sediment, respectively. Our evaluation
      of the ecotoxicological status showed high coincidences with the ecological
      status, established according to the WFD, especially when ecosystem disruption
      due to numerous stressors (presence of metals and organic pollution) was
      observed. These results allow us to confirm that, when chemical stressors affect
      the ecosystem functioning negatively, an ecotoxicological approach, provided by
      suitable bioassays in pore water and whole sediment, could detect these changes
      with accurate sensitivity. 

PMID- 25046986
TI  - A clinical review of PDT for cutaneous malignancies.
AB  - More critical than for most other anatomy, intervention to cutaneous malignancy
      must not only be therapeutically successful but also achieve excellent cosmetic
      and functional outcome. As it can achieve those ends, PDT has moved to the
      forefront in the management of skin cancer. A number of well designed clinical
      trials and large patient series have reported outstanding outcomes for many
      histologies. This paper will review the rationale and outcomes of cutaneous PDT
      to malignancy using both topical and systemic photosensitizers. The benefits and
      drawbacks of cutaneous PDT are also examined. 

PMID- 25046987
TI  - Early apoptotic responses in transgenic mouse mammary carcinoma for photodynamic
      therapy.
AB  - BACKGROUND: Male transgenic mice expressing the human RAS gene on an FVB strain
      background develop adenocarcinoma of the breast between 7 and 8 weeks of age. We
      have utilized this mammary tumour model to investigate apoptotic responses
      following photodynamic therapy (PDT) with a chlorin-based, water-soluble
      photosensitizer. METHODS: Detection of apoptosis was accomplished by use of the
      antibody M30 against a neo-epitope of caspase-cleaved cytokeratin 18 that becomes
      available at an early stage of the apoptotic cascade. Mice bearing multiple
      tumours were injected with the photosensitizer intraperitoneally, and following a
      drug-light interval of 96h, 40J/cm(2) of 652nm laser light was applied to one
      tumour per animal, while the other tumours were protected from light to serve as
      host controls. The M30 antibody was used for standard immunohistochemistry of
      tumour sections and flow cytometric detection of epitope expression coupled to
      cell cycle analysis in tumour cell populations retrieved from paraffin blocks.
      RESULTS: M30 staining was significantly increased within 2h following light
      treatment and persisted until 96h after treatment. Flow cytometric analysis for
      the S-phase fraction (SPF) of tumour cells post-PDT showed a substantial decrease
      in SPF at 2h post PDT, and recovery of SPF within 96h. CONCLUSIONS: Cytokeratin
      18 cleavage seems to be both an early and ongoing event during the cellular
      response to PDT. Calculating the M30/SPF ratio at both 2h and 96h suggested
      distinct cellular dynamics at early and late time points, and we propose the
      M30/SPF ratio as a tumour dynamic index (TDI) to monitor events post PDT.

PMID- 25046989
TI  - Apoptosis and expression of cytokines triggered by pyropheophorbide-a methyl
      ester-mediated photodynamic therapy in nasopharyngeal carcinoma cells.
AB  - The photodynamic properties of pyropheophorbide-a methyl ester (MPPa), a semi
      synthetic photosensitizer derived from chlorophyll a, were evaluated in a human
      nasopharyngeal carcinoma HONE-1 cell line. MPPa was non-toxic to the HONE-1. At
      the concentrations of 0.5-2MUM, MPPa-mediated a drug dose-dependent
      photocytotoxicity in the HONE-1 cells. Confocal microscopy revealed a subcellular
      localization of MPPa in mitochondria and the Golgi apparatus. MPPa PDT-induced
      apoptosis was associated with the collapse of mitochondrial membrane potential,
      release of cytochrome c, the up-regulation of endoplasmic reticulum (ER) stress
      proteins (calnexin, Grp 94 and Grp78), and the activation of caspases-3 and -9.
      The photocytotoxicity was reduced by the corresponding specific caspase
      inhibitors. MPPa PDT-treated HONE-1 cells also up-regulated the gene expression
      of pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) and beta-chemokines
      (MIP-1beta, MPIF-1, and MPIF-2). These results suggest that the MPPa may be
      developed as a chlorophyll-based photosensitizer for the treatment of
      nasopharyngeal carcinoma. 

PMID- 25046988
TI  - Prostate PDT dosimetry.
AB  - We provide a review of the current state of dosimetry in prostate photodynamic
      therapy (PDT). PDT of the human prostate has been performed with a number of
      different photosensitizers and with a variety of dosimetry schemes. The simplest
      clinical light dose prescription is to quantify the total light energy emitted
      per length (J/cm) of cylindrical diffusing fibers (CDF) for patients treated with
      a defined photosensitizer injection per body weight. However, this approach does
      not take into account the light scattering by tissue and usually underestimates
      the local light fluence rate, and consequently the fluence. Techniques have been
      developed to characterize tissue optical properties and light fluence rates in
      vivo using interstitial measurements during prostate PDT. Optical methods have
      been developed to characterize tissue absorption and scattering spectra, which in
      turn provide information about tissue oxygenation and drug concentration.
      Fluorescence techniques can be used to quantify drug concentrations and
      photobleaching rates of photosensitizers. 

PMID- 25046990
TI  - DAFE autofluorescence assessment of oral cavity, larynx and bronchus in head and
      neck cancer patients.
AB  - Head and neck (H&N) cancer patients have a high incidence of local field change
      as well as second primary lung tumours. We have applied the Wolf Diagnostic
      Autofluorescence Endoscopy (DAFE) system in a novel way, combining
      autofluorescence evaluation of both H&N region and bronchial. New H&N cases as
      well as "old" cases with symptoms were included. The DAFE procedure was done
      separate to panendoscopy. The H&N region was examined first; images were recorded
      of the known primary with reference to subsequent resection margins, as well as
      of adjacent mucosa inspecting for additional abnormal sites. Then
      autofluorescence bronchoscopy was performed. Changes in management were only on
      the basis of histology taken because of abnormal autofluorescence. One hundred
      and seven cases were referred, including 96 new cases and 11 old cases.
      Autofluorescence examination of H&N detected sites which led to change of
      management in 11 patients. This included additional sites in nine patients (which
      then either had extra surgery or radiotherapy as a result) and wider resection
      margins were made possible in two patients. In the bronchus there were 21
      significant lesions in 16 patients. Immediate management change occurred in one
      invasive cancer, two microinvasive carcinomas and three carcinomas in situ (in
      four patients). There were 15 sites of severe and moderate dysplasia in 12
      patients. None of these bronchoscopic lesions were detectable on CT chest.
      Therefore, overall an immediate change in management occurred in 15 of 107
      patients (14% of patients). This combined procedure yielded a significant number
      of lesions particularly as a simple addition to preoperative work-up in new H&N
      cancer cases. 

PMID- 25046991
TI  - Clinical study of Photofrin photodynamic therapy for the treatment of relapse
      nasopharyngeal carcinoma.
AB  - OBJECTIVES: To evaluate the clinical response and adverse effects of Photofrin
      photodynamic therapy (PDT) in patients with relapse nasal pharyngeal cancer.
      METHODS: Thirty patients with relapse nasal pharyngeal cancer were randomly
      divided into PDT group and chemotherapy group. In PDT group, patients received
      intravenous administration of Photofrin (2mg/kg b.w.) and 48h later light (200
      300J/cm) was delivered by a 630nm diode laser through a cylinder diffuser under
      endoscopic assistance. Two days after PDT the necrotic tissues were removed and
      newly identified sites were subject to another round of light irradiation. In
      chemotherapy group, the routine cisplatin and 5-fluorouracil (DDP/5-FU) remedy
      was used. Endoscopic and radiological examinations were performed during 6 months
      follow-up. The Karnofsy Score was used to evaluate the quality of life. RESULTS:
      The local response and nasal cavity obstruction remission rate in PDT group were
      better than that in chemotherapy group. The Karnofsy Score was also improved in
      PDT group. CONCLUSION: This pilot study suggests that Photofrin PDT is effective
      and safe in treatment of advanced nasal pharyngeal cancer and management of nasal
      obstruction.

PMID- 25046992
TI  - The use of photodynamic therapy using 630nm laser light and porfimer sodium for
      the treatment of oral squamous cell carcinoma.
AB  - PDT has been demonstrated in clinical studies to be an efficacious method for the
      treatment of dysplastic, microinvasive and early forms of cancer. The advantage
      of PDT for early carcinomas of the oral cavity is the ability to preserve normal
      tissues while effectively treating cancers up to 1cm in depth. The case presented
      here successfully demonstrates the ability to use PDT to treat maxillary gingival
      squamous cell carcinoma thereby sparing the use of surgery or radiation therapy
      at this point in the management of the disease. 

PMID- 25046993
TI  - Highlights of the symposium on medical physics (III International Symposium on
      Medical Physics) 20-23rd September 2006, Ustron, Poland.

PMID- 25046994
TI  - Disease modifying effect of chronic oral treatment with a neurotrophic
      peptidergic compound in a triple transgenic mouse model of Alzheimer's disease.
AB  - Besides the presence of amyloid beta (Abeta) plaques and neurofibrillary tangles,
      neurogenesis and synaptic plasticity are markedly impaired in Alzheimer's disease
      (AD) possibly contributing to cognitive impairment. In this context, neurotrophic
      factors serve as a promising therapeutic approach via utilization of regenerative
      capacity of brain to shift the balance from neurodegeneration to neural
      regeneration. However, besides more conventional "bystander" effect, to what
      extent can neurotrophic compounds affect underlying AD pathology remains
      questionable. Here we investigated the effect of chronic oral treatment with a
      ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac
      DGGL(A)G-NH2), on disease pathology both at moderate and severe stages in a
      transgenic mouse model of AD. 3xTg-AD and wild type female mice were treated for
      12months with P021 or vehicle diet starting at 9-10months of age. A significant
      reduction in abnormal hyperphosphorylation and accumulation of tau at known major
      AD neurofibrillary pathology associated sites was observed. The effect of P021 on
      Abeta pathology was limited to a significant decrease in soluble Abeta levels and
      a trend towards reduction in Abeta plaque load in CA1 region of hippocampus,
      consistent with reduction in Abeta generation and not clearance. This disease
      modifying effect was probably via increased brain derived neurotrophic factor
      (BDNF) expression mediated decrease in glycogen synthase kinase-3-beta (GSK3beta)
      activity we found in P021 treated 3xTg-AD mice. P021 treatment also rescued
      deficits in cognition, neurogenesis, and synaptic plasticity in 3xTg-AD mice.
      These findings demonstrate the potential of the neurotrophic peptide mimetic as a
      disease modifying therapy for AD. 

PMID- 25046995
TI  - A cell culture model for monitoring alpha-synuclein cell-to-cell transfer.
AB  - The transfer of alpha-synuclein (alpha-syn) between cells has been proposed to be
      the primary mechanism of disease spreading in Parkinson's disease. Several
      cellular models exist that monitor the uptake of recombinant alpha-syn from the
      culture medium. Here we established a more physiologically relevant model system
      in which alpha-syn is produced and transferred between mammalian neurons. We
      generated cell lines expressing either alpha-syn tagged with fluorescent proteins
      or fluorescent tags alone then we co-cultured these cell lines to measure protein
      uptake. We used live-cell imaging to demonstrate intercellular alpha-syn transfer
      and used flow cytometry and high content analysis to quantify the transfer. We
      then successfully inhibited intercellular protein transfer genetically by down
      regulating dynamin or pharmacologically using dynasore or heparin. In addition,
      we differentiated human induced pluripotent stem cells carrying a triplication of
      the alpha-syn gene into dopaminergic neurons. These cells secreted high levels of
      alpha-syn, which was taken up by neighboring neurons. Collectively, our co
      culture systems provide simple but physiologically relevant tools for the
      identification of genetic modifiers or small molecules that inhibit alpha-syn
      cell-to-cell transfer. 

PMID- 25046996
TI  - Spreading of alpha-synuclein in the face of axonal transport deficits in
      Parkinson's disease: a speculative synthesis.
AB  - Parkinson's disease (PD) is mainly attributed to degeneration of dopamine neurons
      in the substantia nigra, but its etiopathogenesis also includes impaired protein
      clearance and axonal transport dysfunction, among others. The spread of alpha
      synuclein (alpha-syn) aggregates from one neuron to another, in a prion-like
      manner, is hypothesized to contribute to PD progression. Axonal transport is
      likely to play a crucial role in this movement of alpha-syn aggregates between
      brain regions. At the same time, deficits in axonal transport are suggested to
      contribute to neuronal failure in PD. In this review, we discuss the apparent
      contradiction that axonal transport might be essential for disease progression,
      while dysfunction of axonal transport could simultaneously be a cornerstone of PD
      pathogenesis. We speculate around models that reconcile how axonal transport can
      play such a paradoxical role. 

PMID- 25046998
TI  - A poorly becoming leadership.

PMID- 25046999
TI  - 'Playing favourites': Is there bias during patient selection by registrars in an
      Australian paediatric emergency department?
AB  - AIM: Overseas studies have suggested a bias in emergency department patient
      selection between paediatric and emergency medicine trainees. This study aimed to
      detect whether a similar bias existed in an Australasian setting. Specifically,
      we sought to determine whether vocational trainees choose patients based on
      presenting complaint, triage category or patient age. METHODS: A retrospective
      review of patients attending the Monash Medical Centre Paediatric Emergency
      Department (PED) was conducted during four consecutive registrar rotations from
      July 2010 to March 2011. A 2-week period during the middle of each term was
      chosen, and data were collected from times when both emergency and paediatric
      registrars were present in the department. RESULTS: A total of 1222 patient
      records were reviewed. Emergency registrars saw 278 patients, and paediatric
      registrars saw 413 patients. Of those seen by emergency registrars, 62.9% had
      medical diagnoses, and 37.1% had non-medical diagnoses; 14.4% were triaged as
      high acuity, and 85.6% were low acuity. Of those seen by paediatric registrars,
      70% had medical diagnoses, and 30% had non-medical diagnoses, while 15.9% were
      high acuity, and 84.1% were low acuity. Emergency registrars saw 2.5% neonates,
      6.5% adolescents. Paediatric registrars saw 3.6% neonates and 6.1% adolescents.
      There was no significant difference between paediatric and emergency registrars
      in selecting patients. CONCLUSIONS: Bias does not appear to exist in the
      selection of patients in this Australasian PED. Further study should address the
      impact of unbiased patient selection on emergency department efficiency and
      trainee education.

PMID- 25046997
TI  - Therapeutic perspectives of epigenetically active nutrients.
AB  - Many nutrients are known for a wide range of activities in prevention and
      alleviation of various diseases. Recently, their potential role in regulating
      human health through effects on epigenetics has become evident, although specific
      mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged
      as a new and promising field in current epigenetics research in the past few
      years. In particular, polyphenols, as part of the central dynamic interaction
      between the genome and the environment with specificity at physiological
      concentrations, are well known to affect mechanisms underlying human health. This
      review summarizes the effects of dietary compounds on epigenetic mechanisms in
      the regulation of gene expression including expression of enzymes and other
      molecules responsible for drug absorption, distribution, metabolism and excretion
      in cancer, metabolic syndrome, neurodegenerative disorders and hormonal
      dysfunction.

PMID- 25047000
TI  - CerebrolysinTM efficacy in a transgenic model of tauopathy: role in regulation of
      mitochondrial structure.
AB  - BACKGROUND: Alzheimer's Disease (AD) and Fronto temporal lobar dementia (FTLD)
      are common causes of dementia in the aging population for which limited
      therapeutical options are available. These disorders are associated with Tau
      accumulation. We have previously shown that CerebrolysinTM (CBL), a neuropeptide
      mixture with neurotrophic effects, ameliorates the behavioral deficits and
      neuropathological alterations in amyloid precursor protein (APP) transgenic (tg)
      mouse model of AD by reducing hyper-phosphorylated Tau. CBL has been tested in
      clinical trials for AD, however it's potential beneficial effects in FTLD are
      unknown. For this purpose we sought to investigate the effects of CBL in a tg
      model of tauopathy. Accordingly, double tg mice expressing mutant Tau under the
      mThy-1 promoter and GSK3beta (to enhance Tau phosphorylation) were treated with
      CBL and evaluated neuropathologically. RESULTS: Compared to single Tau tg mice
      the Tau/GSK3beta double tg model displayed elevated levels of Tau phosphorylation
      and neurodegeneration in the hippocampus. CBL treatment reduced the levels of Tau
      phosphorylation in the dentate gyrus and the degeneration of pyramidal neurons in
      the temporal cortex and hippocampus of the Tau/GSK3beta double tg mice.
      Interestingly, the Tau/GSK3beta double tg mice also displayed elevated levels of
      Dynamin-related protein-1 (Drp-1), a protein that hydrolyzes GTP and is required
      for mitochondrial division. Ultrastructural analysis of the mitochondria in the
      Tau/GSK3beta double tg mice demonstrated increased numbers and fragmentation of
      mitochondria in comparison to non-tg mice. CBL treatment normalized levels of Drp
      1 and restored mitochondrial structure. CONCLUSIONS: These results suggest that
      the ability of CBL to ameliorate neurodegenerative pathology in the tauopathy
      model may involve reducing accumulation of hyper-phosphorylated Tau and reducing
      alterations in mitochondrial biogenesis associated with Tau.

PMID- 25047001
TI  - The effect of primary delivery of the anterior compared with the posterior
      shoulder on perineal trauma: a study protocol for a randomized controlled trial.
AB  - BACKGROUND: Approximately 85% of vaginal deliveries are accompanied by perineal
      trauma. The objective of this trial is to compare the incidence and degree of
      perineal trauma after primary delivery of the anterior compared with the
      posterior shoulder during vaginal birth. The hypothesis is that primary delivery
      of the posterior shoulder reduces the rate and degree of perineal trauma.
      METHODS/DESIGN: This is a single-centre, randomized controlled trial, with
      computer-generated randomization in a 1:1 allocation ratio. Women planning their
      first vaginal delivery (n = 650) are randomized to primary delivery of either the
      anterior or posterior shoulder. The primary outcome is any perineal trauma.
      Additional outcomes are the perineal injury subtypes, postpartum bleeding,
      umbilical artery pH, Apgar score at 5 minutes and any neonatal birth trauma.
      Perineal trauma is assessed by a midwife or doctor blinded to the method of
      shoulder delivery. All midwives are trained in the two methods of shoulder
      delivery and in the grading of perineal tears. The trial is being undertaken at a
      Danish community hospital with 1,600 yearly deliveries. Data will be analyzed
      according to the intention-to-treat principle. Recruitment started in January
      2013 and the trial is planned to proceed for 24 months. DISCUSSION: Most delivery
      assistance techniques are based on tradition and heritage and lack objective
      evidence. This trial provides an example of how vaginal delivery techniques can
      be evaluated in a randomized controlled trial. The results of this trial will
      clarify the role that delivery of the shoulders has on perineal trauma and
      thereby provide knowledge to recommendations on birthing technique. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01937546.

PMID- 25047002
TI  - Inhibition of the androgen receptor by mineralocorticoids at levels
      physiologically achieved in serum in patients treated with abiraterone acetate.
AB  - BACKGROUND: Abiraterone acetate (AA), a highly potent CYP17A1 inhibitor, has
      demonstrated marked clinical benefit in patients with metastatic castration
      resistant prostate cancer (CRPC). Phase I trials of AA without prednisone showed
      significant elevation of serum mineralocorticoid concentrations. The aim of this
      study was to elucidate the biological significance of elevated mineralocorticoid
      levels on androgen receptor (AR) activity in prostate cancer (PC) cells. METHODS:
      Fluorescence resonance energy transfer (FRET) assay was used to assess the effect
      of mineralocorticoids on androgen-induced conformational change of the AR. LAPC4,
      LNCaP and LN-AR cells that were cultured and treated with androgens were exposed
      to mineralocorticoids at varying concentrations, including levels measured in the
      serum of AA-treated patients in a phase I trial. AR-dependent transcriptional
      activity and cell growth were measured in these cell lines to determine the
      biological impact of mineralocorticoids on PC cells. RESULTS: Corticosterone (CS)
      and deoxycorticosterone (DOC) inhibited androgen-induced conformational change of
      the AR in the FRET assay. CS inhibited AR-dependent transcriptional activity and
      cell growth at concentrations comparable to those measured in the serum of AA
      treated patients. DOC inhibited AR transcriptional activity and cell growth at 10
      fold greater concentrations than measured in the serum of AA-treated patients.
      CONCLUSIONS: Mineralocorticoids directly inhibit androgen-induced conformational
      change of the AR. CS inhibits AR transcriptional activity and PC cell growth at
      concentrations found in the serum of patients treated with AA. Further
      investigation of the potential therapeutic implications of mineralocorticoids in
      AA-treated CRPC patients is warranted.

PMID- 25047003
TI  - Clinical trials and the right to remain silent.

PMID- 25047004
TI  - Body region dissatisfaction predicts attention to body regions on other women.
AB  - The proliferation of "idealized" (i.e., very thin and attractive) women in the
      media has contributed to increasing rates of body dissatisfaction among women.
      However, it remains relatively unknown how women attend to these images: does
      dissatisfaction predict greater or lesser attention to these body regions on
      others? Fifty healthy women (mean age=21.8 years) viewed images of idealized and
      plus-size models; an eye-tracker recorded visual attention. Participants also
      completed measures of satisfaction for specific body regions, which were then
      used as predictors of visual attention to these regions on models. Consistent
      with an avoidance-type process, lower levels of satisfaction with the two regions
      of greatest reported concern (mid, lower torso) predicted less attention to these
      regions; greater satisfaction predicted more attention to these regions. While
      this visual attention bias may aid in preserving self-esteem when viewing
      idealized others, it may preclude the opportunity for comparisons that could
      improve self-esteem. 

PMID- 25047005
TI  - Antibiotic-potentiation activities of four Cameroonian dietary plants against
      multidrug-resistant Gram-negative bacteria expressing efflux pumps.
AB  - BACKGROUND: The continuous spread of multidrug-resistant (MDR) bacteria,
      partially due to efflux pumps drastically reduced the efficacy of the antibiotic
      armory, increasing the frequency of therapeutic failure. The search for new
      compounds to potentiate the efficacy of commonly used antibiotics is therefore
      important. The present study was designed to evaluate the ability of the methanol
      extracts of four Cameroonian dietary plants (Capsicum frutescens L. var.
      facilulatum, Brassica oleacera L. var. italica, Brassica oleacera L. var. butyris
      and Basilicum polystachyon (L.) Moench.) to improve the activity of commonly used
      antibiotics against MDR Gram-negative bacteria expressing active efflux pumps.
      METHODS: The qualitative phytochemical screening of the plant extracts was
      performed using standard methods whilst the antibacterial activity was performed
      by broth micro-dilution method. RESULTS: All the studied plant extracts revealed
      the presence of alkaloids, phenols, flavonoids, triterpenes and sterols. The
      minimal inhibitory concentrations (MIC) of the studied extracts ranged from 256
      1024 MUg/mL. Capsicum frutescens var. facilulatum extract displayed the largest
      spectrum of activity (73%) against the tested bacterial strains whilst the lower
      MIC value (256 MUg/mL) was recorded with Basilicum polystachyon against E.
      aerogenes ATCC 13048 and P. stuartii ATCC 29916. In the presence of PAbetaN, the
      spectrum of activity of Brassica oleacera var. italica extract against bacteria
      strains increased (75%). The extracts from Brassica oleacera var. butyris,
      Brassica oleacera var. italica, Capsicum frutescens var. facilulatum and
      Basilicum polystachyon showed synergistic effects (FIC <= 0.5) against the
      studied bacteria, with an average of 75.3% of the tested antibiotics. CONCLUSION:
      These results provide promising information for the potential use of the tested
      plants alone or in combination with some commonly used antibiotics in the fight
      against MDR Gram-negative bacteria.

PMID- 25047006
TI  - Globotriaosylsphingosine (lyso-Gb3) might not be a reliable marker for monitoring
      the long-term therapeutic outcomes of enzyme replacement therapy for late-onset
      Fabry patients with the Chinese hotspot mutation (IVS4+919G>A).
AB  - BACKGROUND: In Taiwan, DNA-based newborn screening showed a surprisingly high
      incidence (1/875 in males and 1/399 in females) of a cardiac Fabry mutation (IVS4
      + 919G > A). However, the natural course, long-term treatment outcomes and
      suitable biomarkers for monitoring the therapeutic outcomes of these patients are
      largely unknown. METHODS: Fabry disease (FD) patients who had received enzyme
      replacement therapy (ERT) for more than 1 year were enrolled in this study from
      December 2008 to April 2013. Periodic echocardiography and serum
      globotriaosylsphingosine (lyso-Gb3) analysis were carried out. Before and after
      ERT, left ventricular mass index (LVMI) and serum lyso-Gb3 level were compared
      and the correlation between the change of LVMI and the change of serum lyso-Gb3
      were also analyzed. RESULTS: Thirty-six patients, in four patient groups, were
      enrolled: (1) 16 males with IVS4 + 919G > A mutation; (2) 7 females with IVS4 +
      919G > A mutation; (3) 2 males with classical mutations; and (4) 11 females with
      classical mutations. The follow-up period was 13-46 months. There were
      significant LVMI reductions after ERT in all four groups after excluding
      confounding factors. However, interestingly, serum lyso-Gb3 decreased
      significantly in the early period after ERT in all groups, but increased
      gradually after an average of 11.1 months after ERT in late-onset male and female
      Fabry groups, even when their LVMI still decreased or remained stable.
      Furthermore, there was no correlation between the change of serum lyso-Gb3 and
      the change of LVMI in both classical and IVS4 + 919G > A FD patients. CONCLUSION:
      Although lyso-Gb3 has a high diagnostic sensitivity in late-onset Fabry patients
      and has a good response to ERT during the early stages, it might not be a
      reliable marker for monitoring the long-term therapeutic outcomes of ERT for late
      onset Fabry patients with the Chinese hotspot mutation (IVS4 + 919G > A).

PMID- 25047007
TI  - 'For me... it's a miracle': Injecting beauty among kathoeis in a provincial Thai
      city.
AB  - BACKGROUND: The Thai term kathoei refers to non-gender-normative females, males
      and intersexual individuals at different stages of the transitional spectrum with
      recognized social and cultural roles in society. Nevertheless, kathoeis are only
      tolerated in Thai society. Many kathoeis seek social acceptance through beauty
      and turn to the off-label injection of various 'beauty drugs'. METHODS: The first
      author conducted an ethnographic study of injection parties at a wedding studio
      in a Central Thai provincial city between April and September 2011. Data were
      gathered through participant observation, focus group discussions and narrative
      interviews with six participants. All data were collected and analyzed in Thai,
      and later translated. RESULTS: While injection parties provide opportunities for
      kathoeis to socialize, bond, and share experiential knowledge on chemically
      assisted transformation, they also reproduce ideologies of gender, beauty and
      sexuality that reinforce the notion that if a kathoei is to maintain her beauty,
      she must use medicines more frequently and in higher doses. CONCLUSION: Injection
      parties among Thai kathoeis feature drug use that is entirely reasonable in terms
      of their own lay knowledge. Empowering kathoeis, by providing accessible
      information on chemicals and health in a way that reflects the complexity and
      diversity of their practices, would be one way to reduce health risks. Society
      must give more long-term options to kathoeis to build their sense of self, based
      on things besides being beautiful.

PMID- 25047008
TI  - Timing properties of phosphor-coated polished LSO crystals.
AB  - This study investigates a time-of-flight (TOF)-depth-of-interaction (DOI)
      detector design for positron emission tomography (PET), based on phosphor-coated
      lutetium oxyorthosilicate (LSO) scintillator crystals coupled to fast single
      channel photomultiplier tubes. Interaction of the scintillation light with the
      phosphor coating changes the pulse shape in a depth-dependent manner. 3 * 3 * 10
      mm(3) LSO scintillation crystals with polished surfaces were characterized, with
      and without phosphor coating, to assess DOI capability and timing properties. Two
      different phosphor coating geometries were studied: coating of the top surface of
      the crystal, and the top plus half of the crystal sides. There was negligible
      depth dependency in the decay time when coating only the top surface, however
      there was a ~10 ns difference in end-to-end decay time when coating the top plus
      half of the crystal sides, sufficient to support the use of three DOI bins (3.3
      mm DOI bin width). The rise time of the half-coated phosphor crystal was slightly
      faster at all depths, compared to uncoated crystals, however the signal amplitude
      was lower. Phosphor coating resulted in depth-dependent photopeak positions with
      an energy resolution of 13.7%, at a depth of 1 mm, and 15.3%, at a depth of 9 mm,
      for the half-coated crystal. Uncoated LSO crystals showed no change in photopeak
      position as a function of depth, with an energy resolution of 10.4%. The head-on
      coincidence timing resolution (CTR) of two uncoated LSO crystals was 287 ps using
      constant fraction discrimination for time pick-off. With phosphor coating, the
      CTR of the top-coated crystal was 314 ps, compared to 384 ps for the half-coated
      crystal. We demonstrate that the trade-off between timing resolution and DOI
      resolution can be controlled by the phosphor coating geometry. Here we present
      preliminary results demonstrating that good DOI resolution can be achieved with
      only a modest 26% degradation in CTR. 

PMID- 25047009
TI  - Subcellular localization of KL-6 mucin in intraductal papillary mucinous neoplasm
      of the pancreas.
AB  - This study aimed to clarify the expression profile of KL-6 mucin in intraductal
      papillary mucinous neoplasm (IPMN) and its relation to tumor malignancy.
      Expression of KL-6 mucin in 38 IPMNs (intraductal papillary mucinous adenoma
      (IPMA), 24 cases; minimally invasive intraductal papillary mucinous carcinoma (MI
      IPMC), 8 cases; invasive carcinoma originating from IPMC (IC-IPMC), 6 cases) and
      66 pancreatic ductal adenocarcinomas (PDACs) was evaluated immunohistochemically.
      IC-IPMCs and MI-IPMCs had positive staining of KL-6 mucin whereas 58% of IPMAs
      tested negative. Subcellular localization of KL-6 mucin varied among IPMNs
      whereas all of the PDAC had positive expression in the circumferential membrane
      and cytoplasm of cancer cells. IC-IPMCs and MI-IPMCs had a higher frequency of
      circumferential membrane and cytoplasmic localization of KL-6 mucin than did
      IPMAs. These results suggest that localization of KL-6 mucin could be used to
      predict the malignancy of IPMN. 

PMID- 25047010
TI  - Stabilization of a two-coordinate mononuclear cobalt(0) compound.
AB  - Compound (Me2 -cAAC:)2 Co(0) (2; Me2 -cAAC:=cyclic (alkyl) amino carbene; :C(CH2
      )(CMe2 )2 N-2,6-iPr2 C6 H3 ) was synthesized by the reduction of the precursor
      (Me2 -cAAC:)2 Co(I) Cl (1) with KC8 in THF. The cyclic voltammogram of 1
      exhibited one-electron reduction, which suggests that synthesis of a bent 2
      metallaallene (2) from 1 should be possible. Compound 2 contains one cobalt atom
      in the formal oxidation state zero, which is stabilized by two Me2 -cAAC:
      ligands. Bond lengths from X-ray diffraction are 1.871(2) and 1.877(2) A with a C
      Co-C bond angle of 170.12(8) degrees . The EPR spectrum of 2 exhibited a broad
      resonance attributed to the unique quasi-linear structure, which favors near
      degeneracy and gives rise to very rapid relaxation conditions. The cAAC?Co bond
      in 2 can be considered as a typical Dewar-Chatt-Duncanson type of bonding, which
      in turn retains 2.5 electron pairs on the Co atom as nonbonding electrons. 

PMID- 25047011
TI  - The use of contralateral knee magnetic resonance imaging to predict meniscal size
      during meniscal allograft transplantation.
AB  - PURPOSE: The purpose of this study was to determine the size of each meniscus and
      compare it with the contralateral limb using conventional knee magnetic resonance
      imaging (MRI) taken from previously uninjured, healthy, young volunteers.
      METHODS: The knee joints of 60 healthy volunteers (aged 21 to 43 years, 30 men
      and 30 women) were enrolled in this study. Standard 3.0-T MRI in a controlled
      setting was used. By use of the mid-coronal images, the height and width of each
      medial and lateral meniscus were measured. By use of the mid-sagittal images, the
      height and width of the anterior and posterior horns of each meniscus was
      measured. The whole length spanning from the most anterior margin to the most
      posterior margin of each meniscus was also measured. Mean, standard deviation,
      and 95% confidence interval values were determined for each measurement. RESULTS:
      There were 3 incomplete discoid lateral menisci (10%) in men and 2 incomplete
      discoid menisci (6.7%) in women. The study group with non-discoid knees comprised
      27 men and 28 women. The power of this study ranged from 0.57 to 0.66. All values
      showed good reliability (intraclass correlation coefficient range, 0.887 to
      0.974). There were no significant differences between right and left menisci (all
      P > .05). There were significant differences between genders. All parameters
      showed significant differences (P < .05) except the medial meniscus width (P =
      .221). CONCLUSIONS: In this small subset of patients, there were no differences
      between right and left meniscal measurements according to MRI. Therefore, when
      one is performing meniscal allograft transplantation, contralateral knee MRI may
      be useful to determine the required size. Identifying both the overall width and
      length of each meniscus is important when preparing an allograft. CLINICAL
      RELEVANCE: Contralateral knee MRI may be used for more accurate meniscal size
      measurement in patients undergoing meniscal allograft transplantation.

PMID- 25047012
TI  - Two-color delay dependent IR probing of torsional isomerization in a [AgL1L2]+
      complex.
AB  - Two-color infrared multiple photon dissociation (2c-IR-MPD) spectroscopy with
      delayed pulses indicates a torsional isomerization in a "ligand-metal-chelate"
      complex [AgL1L2](+). Ab initio calculations reveal the torsional barrier as well
      as the change in vibrational frequencies and IR intensities along the
      isomerization pathway. The current approach bears prospects for further
      elucidation of competing interactions within naked or microsolvated complexes in
      gas phase coordination chemistry. 

PMID- 25047013
TI  - Identification of mechanisms of action of bisphenol a-induced human preadipocyte
      differentiation by transcriptional profiling.
AB  - OBJECTIVE: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is
      correlated with obesity and adipogenesis of human preadipocytes. However, the
      mechanism of action of BPA-induced human adipogenesis remains to be determined.
      METHODS: Primary human preadipocytes were differentiated in the presence of 50 uM
      BPA or 1 uM dexamethasone (DEX) for 48 hours. Potential mechanisms of BPA-induced
      adipogenesis were evaluated using gene expression microarray analysis. RESULTS:
      Microarray analysis revealed 373 differentially expressed genes following BPA
      treatment, including upregulation of sterol regulatory element binding factor 1
      (SREBF1), a key regulator of lipid metabolism. For DEX-treated preadipocytes,
      2167 genes were differentially expressed, including upregulation of the
      adipogenic marker lipoprotein lipase. Ingenuity Pathway Analysis was used to
      identify functional annotations of the gene expression changes associated with
      response to BPA and DEX. BPA exposure was associated with expression changes in
      the genes involved in triacylglycerol accumulation while DEX was linked to
      triacylglycerol and fatty acid metabolism. The analysis also revealed enrichment
      of genes following BPA exposure in the thyroid-receptor/retinoic X receptor
      (TR/RXR) and mammalian target of rapamycin (mTOR) signaling pathways.
      CONCLUSIONS: Our data suggest that potential mechanisms of action of BPA-induced
      adipogenesis involve SREBF1, the TR/RXR, and the mTOR pathways.

PMID- 25047014
TI  - Cadmium and mercury accumulation in European hare (Lepus europaeus): age
      dependent relationships in renal and hepatic tissue.
AB  - A total of 63 European hares have been collected from five Serbian agricultural
      regions. The hares assayed were divided into four age groups (3-6 months, 12
      months, 12-24 months, and 24-36 months) and investigated upon presence at cadmium
      (Cd) and mercury (Hg) in the kidney and liver. The positive significant
      correlation (Ps-Pearson's coefficient) between Cd concentrations in the kidney
      and liver within age group the 3-6 months was found (Ps = 0.81, p < 0.001).
      Differences between Cd content in the kidney in comparison to liver were
      significant within all presented age groups (p < 0.001). Differences between
      recorded Hg levels in the kidney were not significant between presented age
      groups (p > 0.05). Statistically significant differences were registered between
      Hg content in the liver of the hares aged 24-36 and 12 months (p < 0.05). There
      were no statistically significant correlations registered between Hg
      concentrations in the kidney and liver within any particular age group (p >
      0.05). The strong statistically significant associations were registered between
      Cd and Hg content in the liver (Cd L/Hg L) in the age group 3-6 and 12-24 months
      (Cd L/Hg L, Ps = 0.94; p < 0.001 and Ps = 0.91; p < 0.001, respectively). The
      polynomial regression model used for graphing the observed data seems to be a
      method for modeling the relationship between measured Cd and Hg concentrations in
      the liver and kidney as first approximation for bioaccumulation in hares.

PMID- 25047015
TI  - Using enriched stable isotope technique to study Cu bioaccumulation and
      bioavailability in Corbicula fluminea from Taihu Lake, China.
AB  - In this study, we measured trace metals (Cd, Cr, Cu, Ni, Pb, and Zn) in water and
      sediment from representative sites of Taihu Lake, with focus on the analysis of
      trace metal accumulation in Corbicula fluminea (bivalve). The results showed that
      the quality of water in Taihu Lake was generally good and the correlation was not
      found between Cu bioaccumulation in C. fluminea and the concentration in water
      and sediment. Thus, using the stable isotope tracer method, we studied Cu uptake
      from the water phase, the assimilation of Cu from the food phase, and the efflux
      of Cu in vivo by C. fluminea. The result revealed that this species exhibited a
      relatively lower efflux rate constant of Cu compared with other zoobenthos
      species. Using a simple bioenergetics-based kinetic model, Cu concentrations in
      the C. fluminea were calculated with the measured efflux rate. We put forward a
      novel method, which was taking the influence of biological kinetic on metal
      bioaccumulation into account to explain the field survey data.

PMID- 25047016
TI  - Diagnosis and treatment of autoimmune pancreatitis types 1 and 2.
AB  - BACKGROUND: Autoimmune pancreatitis (AIP) is characterized by diffuse or focal
      swelling of the pancreas. AIP has been divided into types 1 and 2. The aim of the
      study was to evaluate and compare the clinicopathological characteristics,
      therapy and outcome of patients with AIP. METHODS: The medical records of
      patients diagnosed with AIP between January 2003 and July 2011 were reviewed.
      Characteristics of patients with AIP types 1 and 2 were compared with those of
      patients with pancreatic ductal adenocarcinoma (PDAC). RESULTS: AIP was
      classified as type 1 in 40 patients and type 2 in 32 according to the HISORt
      (Histology, Imaging, Serology, Other organ involvement, Response to therapy)
      criteria. Patients with histologically confirmed AIP type 2 were younger than
      those with type 1 (P = 0.005). Some 30 of 32 patients with AIP type 2 were found
      to have a localized tumour-like pancreatic mass and underwent pancreatectomy,
      compared with only 16 of 40 with type 1 (P < 0.001). Three of 25 patients with
      AIP type 2 presented with raised serum levels of IgG4 compared with 21 of 38 with
      type 1 (P < 0.001). There was no difference in symptoms and involvement of other
      organs between AIP types 1 and 2. Presentation with weight loss was more common
      among patients with PDAC than those with AIP, but there was no difference in pain
      or jaundice between the groups. Raised serum carbohydrate antigen 19-9 levels
      were more prevalent in patients with PDAC. CONCLUSION: Patients with AIP type 2
      frequently present with abdominal pain and a tumour-like mass. Differentiating
      AIP from PDAC is difficult, so making the clinical decision regarding operative
      versus conservative management is challenging.

PMID- 25047017
TI  - Modern radiopharmaceutical solutions and up-to-date technologies, at the 3rd
      Balkan Congress of Nuclear Medicine.

PMID- 25047018
TI  - The future of nuclear medicine imaging of neuroendocrine tumors: on a clear day
      one might see forever....

PMID- 25047019
TI  - Frequency, distribution and time trends of types of leisure-time physical
      activity in Brazil, 2006-2012.
AB  - OBJECTIVES: To describe the frequency and the distribution of the main types of
      leisure time physical activity (LTPA) practiced by Brazilian adults in 2012 and
      to observe their time trends from 2006 to 2012. METHODS: Cross-sectional data
      from the Brazilian surveillance system of risk and protective factors for non
      transmissible chronic diseases from 2006 to 2012 (around 54,000 adults aged 18
      years or older in all Brazilian State capitals interviewed yearly). Participants
      were asked whether they had practiced any type of exercise or sport in the last 3
      months, and if so which type. Linear regression was used to identify trends of
      the five most cited LTPA. RESULTS: In 2012, walking was reported as the main LTPA
      (18.1 %), followed by strength training/gymnastics (11.2 %) and football (7.2 %).
      Time-trend analysis showed reduction in football (9.1-7.2 %; p = 0.004, beta = 
      0.25, R(2) = 0.79) and increase in strength training/gymnastics (7.9-11.2 %; p =
      0.02, beta = 0.50, R(2) = 0.62) and running (1.7-3.1 %; p < 0.001, beta = 0.22,
      R(2) = 0.93). CONCLUSIONS: Walking was the main type of LTPA. Patterns of LTPA
      types remained relatively stable over the last 7 years.

PMID- 25047020
TI  - Factors explaining the discrepancy between physician and patient global
      assessment of joint and skin disease activity in psoriatic arthritis patients.
AB  - OBJECTIVE: To assess the extent and determinants of discordance in scoring
      between patient global assessment (PtGA) and physician global assessment (PhGA)
      in patients with psoriatic arthritis (PsA). METHODS: A cross-sectional and
      longitudinal analysis of data was conducted in patients attending a large PsA
      clinic. The difference between PtGA and PhGA (each measured on a scale of 0-10,
      with 0 indicating best status and 10 indicating worst status) reflected the
      discrepancy between the PtGA and PhGA of joint and skin activity and could take
      values from -10 (higher rating of disease activity by the patient) to 10 (higher
      rating of disease activity by the physician). Multivariate regression identified
      variables that contributed significantly to each of the outcomes. The proportion
      of variability of each outcome explained by each predictor was expressed by the
      partial R(2) . RESULTS: A total of 565 patients were included in the analysis.
      Patients tended to score their disease worse than their physicians, with greater
      discordance for the joints than for the skin (mean +/- SD 1.68 +/- 2.41 PtGA-PhGA
      difference for joints, and 0.77 +/- 2.66 for skin). Fatigue accounted for 21% of
      the variation in the difference between PtGA and PhGA for joints. Pain (Rpartial2
      = 9%) and disability by Short Form 36 health survey (Rpartial2 = 1.2%) were also
      important factors, each of which led to higher patient rating; whereas increased
      tender joint count (Rpartial2 = 16%) and swollen joint count (Rpartial2 = 1.4%)
      resulted in a higher physician rating of arthritis. CONCLUSION: Fatigue, pain,
      disability, and tender and swollen joint counts were the most important factors
      contributing to discrepancy between patient and physician assessment of joint
      activity.

PMID- 25047021
TI  - Analysis of infections and all-cause mortality in phase II, phase III, and long
      term extension studies of tofacitinib in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the rate of infection and all-cause mortality across
      tofacitinib phase II, phase III, and long-term extension (LTE) studies in
      patients with moderately to severely active rheumatoid arthritis (RA). METHODS:
      Pooled data from studies of tofacitinib in patients with RA were analyzed. In
      these studies, tofacitinib was administered as monotherapy or in combination with
      methotrexate or other nonbiologic disease-modifying antirheumatic drugs. The
      cutoff date for inclusion of data was April 19, 2012. RESULTS: Across phase II,
      phase III, and LTE studies, 4,789 patients received tofacitinib (8,460 patient
      years of exposure). The overall rate of serious infection was 3.09 events per 100
      patient-years (95% confidence interval [95% CI] 2.73-3.49), and rates were stable
      over time. A Cox proportional hazards model showed that age, corticosteroid dose,
      diabetes, and tofacitinib dose were independently linked to the risk of serious
      infection. Lymphocyte counts of <0.5 * 10(3) /mm(3) were rare but were associated
      with an increased risk of treated and/or serious infection. Overall, all-cause
      mortality rates were 0.30 events per 100 patient-years (95% CI 0.20-0.44).
      CONCLUSION: The overall risk of infection (including serious infection) and
      mortality rates in RA patients treated with tofacitinib appear to be similar to
      those observed in RA patients treated with biologic agents. The rates of serious
      infection were stable over time.

PMID- 25047022
TI  - Preparation of MoS2-MoO3 hybrid nanomaterials for light-emitting diodes.
AB  - A facile strategy to prepare MoS2 -MoO3 hybrid nanomaterials is developed, based
      on the heat-assisted partial oxidation of lithium-exfoliated MoS2  nanosheets in
      air followed by thermal-annealing-driven crystallization. The obtained MoS2 -MoO3
      hybrid nanomaterial exhibits p-type conductivity. As a proof-of-concept
      application, an n-type SiC/p-type MoS2 -MoO3 heterojunction is used as the active
      layer for light-emitting diodes. The origins of the electroluminescence from the
      device are theoretically investigated. This facile synthesis and application of
      hybrid nanomaterials opens up avenues to develop new advanced materials for
      various functional applications, such as in electrics, optoelectronics, clean
      energy, and information storage. 

PMID- 25047023
TI  - Automated and reproducible read-across like models for predicting carcinogenic
      potency.
AB  - Several qualitative (hazard-based) models for chronic toxicity prediction are
      available through commercial and freely available software, but in the context of
      risk assessment a quantitative value is mandatory in order to be able to apply a
      Margin of Exposure (predicted toxicity/exposure estimate) approach to interpret
      the data. Recently quantitative models for the prediction of the carcinogenic
      potency have been developed, opening some hopes in this area, but this promising
      approach is currently limited by the fact that the proposed programs are neither
      publically nor commercially available. In this article we describe how two models
      (one for mouse and one for rat) for the carcinogenic potency (TD50) prediction
      have been developed, using lazar (Lazy Structure Activity Relationships), a
      procedure similar to read-across, but automated and reproducible. The models
      obtained have been compared with the recently published ones, resulting in a
      similar performance. Our aim is also to make the models freely available in the
      near future thought a user friendly internet web site. 

PMID- 25047024
TI  - Rapid pretreatment and determination of bisphenol A in water samples based on
      vortex-assisted liquid-liquid microextraction followed by high-performance liquid
      chromatography with fluorescence detection.
AB  - A method for the rapid pretreatment and determination of bisphenol A in water
      samples based on vortex-assisted liquid-liquid microextraction followed by high
      performance liquid chromatography with fluorescence detection was proposed in
      this paper. A simple apparatus consisting of a test tube and a cut-glass dropper
      was designed and applied to collect the floating extraction drop in liquid-liquid
      microextraction when low-density organic solvent was used as the extraction
      solvent. Solidification and melting steps that were tedious but necessary once
      the low-density organic solvent used as extraction solvent could be avoided by
      using this apparatus. Bisphenol A was selected as model pollutant and vortex
      assisted liquid-liquid microextraction was employed to investigate the usefulness
      of the apparatus. High-performance liquid chromatography with fluorescence
      detection was selected as the analytical tool for the detection of bisphenol A.
      The linear dynamic range was from 0.10 to 100 MUg/L for bisphenol A, with good
      squared regression coefficient (r(2) = 0.9990). The relative standard deviation
      (n = 7) was 4.7% and the limit of detection was 0.02 MUg/L. The proposed method
      had been applied to the determination of bisphenol A in natural water samples and
      was shown to be economical, fast, and convenient. 

PMID- 25047025
TI  - A national survey of eating disorder training.
AB  - OBJECTIVE: Eating disorders (EDs) result in the highest mortality rate of all
      psychiatric disorders, and in the United States, approximately one in twenty
      females suffers from an eating disorder. However, training provided within
      residency programs to address the needs of these patients is sparse. The
      objective of this study was to conduct a national survey that assesses the amount
      of EDs training for trainees across five ACGME accredited specialties: internal
      medicine, pediatrics, family medicine, psychiatry, and child and adolescent
      psychiatry. The results of the survey will be used to develop strategies to
      improve eating disorder education among residents. METHOD: Eight hundred eighty
      training coordinators were contacted using information available on the ACGME
      website and asked to complete the survey. RESULTS: Of the 637 responding
      programs, 514 did not offer any scheduled or elective rotations for EDs. Of the
      123 programs offering rotations, only 42 offered a formal, scheduled rotation.
      Child and adolescent psychiatry offered the most clinical experiences, and
      pediatric programs offered the greatest number of didactic hours on EDs.
      DISCUSSION: Training in EDs is limited. Simulated patient encounters, massive
      open online courses, web-based curricula, dedicated rotations and clinical
      experiences, didactic curricula, and brief-training programs may help to improve
      eating disorder diagnostic and treatment skills among trainees.

PMID- 25047026
TI  - Floral neighborhood influences pollinator assemblages and effective pollination
      in a native plant.
AB  - Pollinators represent an important intermediary by which different plant species
      can influence each other's reproductive fitness. Floral neighbors can modify the
      quantity of pollinator visits to a focal species but may also influence the
      composition of visitor assemblages that plants receive leading to potential
      changes in the average effectiveness of floral visits. We explored how the
      heterospecific floral neighborhood (abundance of native and non-native
      heterospecific plants within 2 m * 2 m) affects pollinator visitation and
      composition of pollinator assemblages for a native plant, Phacelia parryi. The
      relative effectiveness of different insect visitors was also assessed to
      interpret the potential effects on plant fitness of shifts in pollinator
      assemblage composition. Although the common non-native Brassica nigra did not
      have a significant effect on overall pollinator visitation rate to P. parryi, the
      proportion of flower visits that were made by native pollinators increased with
      increasing abundance of heterospecific plant species in the floral neighborhood
      other than B. nigra. Furthermore, native pollinators deposited twice as many P.
      parryi pollen grains per visit as did the nonnative Apis mellifera, and visits by
      native bees also resulted in more seeds than visits by A. mellifera. These
      results indicate that the floral neighborhood can influence the composition of
      pollinator assemblages that visit a native plant and that changes in local flower
      communities have the potential to affect plant reproductive success through
      shifts in these assemblages towards less effective pollinators.

PMID- 25047027
TI  - Phenotype of SDHB mutation carriers in the Netherlands.
AB  - SDHB mutation carriers are predisposed to developing paragangliomas (PGLs). The
      objective of this study was to assess genotype-phenotype correlations of a Dutch
      cohort of SDHB mutation carriers and assess potential differences in clinical
      phenotypes related to specific SDHB founder mutations. Forty-seven consecutive
      SDHB mutation carriers were included. Initial screening consisted of measurement
      of 24 h urinary excretion of catecholamines and their metabolites in duplicate,
      repeated annually if initial biochemical screening was negative. Whole-body
      imaging studies with magnetic resonance imaging (MRI) or computed tomography (CT)
      and/or (123)I-MIBG scintigraphy were performed in case of catecholamine excess,
      and MRI or CT scans of thorax, abdomen and pelvis were performed every 2 years
      regardless of catecholamine levels. Repetitive head-and-neck MRI was performed at
      2 year intervals. Mean follow-up was 3.6 +/- 3.6 years. Twenty-seven persons (57
      %) carried the SDHB c.423+1 G>A mutation and seven persons (15 %) the SDHB c.201
      4429_287-933del (exon 3 deletion) mutation. No differences were found in the
      clinical phenotype of carriers of these two specific SDHB mutations. By end of
      follow-up, 49 % of SDHB mutation carriers displayed no biochemical or
      radiological evidence of manifest disease, i.e. they were unaffected carriers.
      Three persons (6 %) had been diagnosed with a pheochromocytoma (PCC), four with a
      sympathetic PGL (sPGL) (9 %), 18 with a HNPGL (38 %), and two persons (4 %) had
      developed a malignant paraganglioma, i.e. metastatic disease. In conclusion, the
      two main Dutch SDHB founder mutations do not differ in clinical expression and
      result in a relatively mild phenotype. Over one-third of SDHB mutation carriers
      develop HNPGL, with sPGL/PCC in only 15 % and malignancy in only 4 %.

PMID- 25047028
TI  - The use of metabolomics in the study of metals in biological systems.
AB  - Metabolomics may be defined as the comprehensive quantitative and/or qualitative
      analysis of all metabolites present in a bio-fluid, cell, tissue, or organism. It
      is essentially the study of biochemical phenotypes (or metabotypes). Metabolic
      profiles are context dependent, and vary in response to a variety of factors
      including environment and environmental stimuli, health status, disease and a
      myriad of other factors; as such, metabolomics has been applied to a wide range
      of fields and has been increasingly utilised to the study of the roles played by
      metals in a range of biological systems as well as, encouragingly, in
      understanding the underlying biochemical mechanisms. The role of metals (and
      metalloids) in biological organisms is complex and the majority of studies in
      this area have been performed in plants but the fields of natural product
      chemistry, human health and even bacterial corrosion of water distribution
      systems have been investigated using this technique. In this review some of the
      novel approaches in which the metabolomics toolbox has been used to unravel the
      roles of metals and metalloids in a range of biological systems are discussed and
      suggestions made for future research.

PMID- 25047029
TI  - Histopathological spectrum of paediatric diffuse intrinsic pontine glioma:
      diagnostic and therapeutic implications.
AB  - Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related
      death in children. In the majority of cases diagnosis is based on clinical and
      MRI findings, resulting in the scarcity of pre-treatment specimens available to
      study. Our group has developed an autopsy-based protocol to investigate the
      histologic and biologic spectrum of DIPG. This has also allowed us to investigate
      the terminal pattern of disease and gain a better understanding of what
      challenges we are facing in treating DIPG. Here, we review 72 DIPG cases with
      well documented clinical history and molecular data and describe the pathological
      features of this disease in relation to clinical and genetic features. Fifty
      three of the samples were autopsy material (7 pre-treatment) and 19 were pre
      treatment biopsy/surgical specimens. Upon histological review, 62 patients had
      high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 had
      WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal tumour
      (PNET). K27M-H3 mutations were exclusively found in tumours with WHO grade II-IV
      astrocytoma histology. K27M-H3.1 and ACVR1 mutations as well as ALT phenotype
      were only found in WHO grade III-IV astrocytomas, while PIK3CA mutations and
      PDGFRA gains/amplifications were found in WHO grade II-IV astrocytomas.
      Approximately 1/3 of DIPG patients had leptomeningeal spread of their tumour.
      Further, diffuse invasion of the brainstem, spinal cord and thalamus was common
      with some cases showing spread as distant as the frontal lobes. These findings
      suggest that focal radiation may be inadequate for some of these patients.
      Importantly, we show that clinically classic DIPGs represent a diverse histologic
      spectrum, including multiple cases which would fit WHO criteria of grade II
      astrocytoma which nevertheless behave clinically as high-grade astrocytomas and
      harbour the histone K27M-H3.3 mutation. This suggests that the current WHO
      astrocytoma grading scheme may not appropriately predict outcome for paediatric
      brainstem gliomas. 

PMID- 25047030
TI  - A gatekeeper helix determines the substrate specificity of Sjogren-Larsson
      Syndrome enzyme fatty aldehyde dehydrogenase.
AB  - Mutations in the gene coding for membrane-bound fatty aldehyde dehydrogenase
      (FALDH) lead to toxic accumulation of lipid species and development of the
      Sjogren-Larsson Syndrome (SLS), a rare disorder characterized by skin defects and
      mental retardation. Here, we present the crystallographic structure of human
      FALDH, the first model of a membrane-associated aldehyde dehydrogenase. The
      dimeric FALDH displays a previously unrecognized element in its C-terminal
      region, a 'gatekeeper' helix, which extends over the adjacent subunit,
      controlling the access to the substrate cavity and helping orientate both
      substrate cavities towards the membrane surface for efficient substrate transit
      between membranes and catalytic site. Activity assays demonstrate that the
      gatekeeper helix is important for directing the substrate specificity of FALDH
      towards long-chain fatty aldehydes. The gatekeeper feature is conserved across
      membrane-associated aldehyde dehydrogenases. Finally, we provide insight into the
      previously elusive molecular basis of SLS-causing mutations. 

PMID- 25047032
TI  - Poly(ADP-ribosyl)ation is required to modulate chromatin changes at c-MYC
      promoter during emergence from quiescence.
AB  - Poly(ADP-ribosyl)ation is a post-translational modification of various proteins
      and participates in the regulation of chromatin structure and transcription
      through complex mechanisms not completely understood. We have previously shown
      that PARP-1, the major family member of poly(ADP-ribose)polymerases, plays an
      important role in the cell cycle reactivation of resting cells by regulating the
      expression of Immediate Early Response Genes, such as c-MYC, c-FOS, JUNB and EGR
      1. In the present work we have investigated the molecular mechanisms by which the
      enzyme induces c-MYC transcription upon serum stimulation of quiescent cells. We
      show that PARP-1 is constitutively associated in vivo to a c-MYC promoter region
      recognized as biologically relevant for the transcriptional regulation of the
      gene. Moreover, we report that serum stimulation causes the prompt accumulation
      of ADP-ribose polymers on the same region and that this modification is required
      for chromatin decondensation and for the exchange of negative for positive
      transcriptional regulators. Finally we provide evidence that the inhibition of
      PARP activity along with serum stimulation impairs c-MYC induction by preventing
      the proper accumulation of histone H3 phosphoacetylation, a specific chromatin
      mark for the activation of Immediate Early Response Genes. These findings not
      only suggest a novel strategy by which PARP-1 regulates the transcriptional
      activity of promoters but also provide new information about the complex
      regulation of c-MYC expression, a critical determinant of the transition from
      quiescence to proliferation. 

PMID- 25047033
TI  - Distinctive genetic activity pattern of the human dental pulp between deciduous
      and permanent teeth.
AB  - Human deciduous and permanent teeth exhibit different developmental processes,
      morphologies, histological characteristics and life cycles. In addition, their
      pulp tissues react differently to external stimuli, such as the pulp sensitivity
      test, dental trauma and pulp therapy materials. These suggest differences in gene
      expression and regulation, and in this study we compared gene-expression profiles
      of the human dental pulp from deciduous and permanent teeth. Pulp tissues from
      permanent premolars and deciduous molars aged 11-14 years were extirpated and
      mRNA was isolated for cDNA microarray analysis, and quantitative real-time PCR
      (qPCR). Other teeth were used for immunohistochemical analysis (IHC). Microarray
      analysis identified 263 genes with a twofold or greater difference in expression
      level between the two types of pulp tissue, 43 and 220 of which were more
      abundant in deciduous and permanent pulp tissues, respectively. qPCR analysis was
      conducted for eight randomly selected genes, and the findings were consistent
      with the cDNA microarray results. IHC confirmed that insulin-like growth factor 2
      mRNA-binding protein 1 (IGF2BP1) was broadly expressed in deciduous dental pulp
      tissue, but minimally expressed in permanent dental pulp tissue.
      Immunohistochemical analysis showed that calbindin 1 (CALB1), leucine-rich repeat
      containing G-protein-coupled receptor 5 (LGR5), and gamma-aminobutyric acid A
      receptor beta 1 (GABRB1) were abundantly expressed in permanent
      predentin/odontoblasts, but only minimally expressed in deciduous dental pulp
      tissue. These results show that deciduous and permanent pulp tissues have
      different characteristics and gene expression, suggesting that they may have
      different functions and responses to therapies focused on pulp or dentin
      regeneration. 

PMID- 25047034
TI  - Activated platelets from diabetic rats cause endothelial dysfunction by
      decreasing Akt/endothelial NO synthase signaling pathway.
AB  - Diabetes is associated with endothelial dysfunction and platelet activation, both
      of which may contribute to increased cardiovascular risk. The purpose of this
      study was to characterize circulating platelets in diabetes and clarify their
      effects on endothelial function. Male Wistar rats were injected with
      streptozotocin (STZ) to induce diabetes. Each experiment was performed by
      incubating carotid arterial rings with platelets (1.65*10(7) cells/mL; 30 min)
      isolated from STZ or control rats. Thereafter, the vascular function was
      characterized in isolated carotid arterial rings in organ bath chambers, and each
      expression and activation of enzymes involved in nitric oxide and oxidative
      stress levels were analyzed. Endothelium-dependent relaxation induced by
      acetylcholine was significantly attenuated in carotid arteries treated with
      platelets isolated from STZ rats. Similarly, treatment with platelets isolated
      from STZ rats significantly reduced ACh-induced Akt/endothelial NO synthase
      signaling/NO production and enhanced TXB2 (metabolite of TXA2), while CD61
      (platelet marker) and CD62P (activated platelet marker) were increased in carotid
      arteries treated with platelets isolated from STZ rats. Furthermore, the
      platelets isolated from STZ rats decreased total eNOS protein and eNOS
      dimerization, and increased oxidative stress. These data provide direct evidence
      that circulating platelets isolated from diabetic rats cause dysfunction of the
      endothelium by decreasing NO production (via Akt/endothelial NO synthase
      signaling pathway) and increasing TXA2. Moreover, activated platelets disrupt the
      carotid artery by increasing oxidative stress.

PMID- 25047035
TI  - Copper chelation selectively kills colon cancer cells through redox cycling and
      generation of reactive oxygen species.
AB  - BACKGROUND: Metals including iron, copper and zinc are essential for
      physiological processes yet can be toxic at high concentrations. However the role
      of these metals in the progression of cancer is not well defined. Here we study
      the anti-tumor activity of the metal chelator, TPEN, and define its mechanism of
      action. METHODS: Multiple approaches were employed, including cell viability,
      cell cycle analysis, multiple measurements of apoptosis, and mitochondrial
      function. In addition we measured cellular metal contents and employed EPR to
      record redox cycling of TPEN-metal complexes. Mouse xenografts were also
      performed to test the efficacy of TPEN in vivo. RESULTS: We show that metal
      chelation using TPEN (5MUM) selectively induces cell death in HCT116 colon cancer
      cells without affecting the viability of non-cancerous colon or intestinal cells.
      Cell death was associated with increased levels of reactive oxygen species (ROS)
      and was inhibited by antioxidants and by prior chelation of copper.
      Interestingly, HCT116 cells accumulate copper to 7-folds higher levels than
      normal colon cells, and the TPEN-copper complex engages in redox cycling to
      generate hydroxyl radicals. Consistently, TPEN exhibits robust anti-tumor
      activity in vivo in colon cancer mouse xenografts. CONCLUSION: Our data show that
      TPEN induces cell death by chelating copper to produce TPEN-copper complexes that
      engage in redox cycling to selectively eliminate colon cancer cells.

PMID- 25047036
TI  - Comparison between culture and a multiplex quantitative real-time polymerase
      chain reaction assay detecting Ureaplasma urealyticum and U. parvum.
AB  - A novel multiplex quantitative real-time polymerase chain reaction (qPCR) for
      simultaneous detection of U. urealyticum and U. parvum was developed and compared
      with quantitative culture in Shepard's 10 C medium for ureaplasmas in urethral
      swabs from 129 men and 66 women, and cervical swabs from 61 women. Using culture
      as the gold standard, the sensitivity of the qPCR was 96% and 95% for female
      urethral and cervical swabs, respectively. In male urethral swabs the sensitivity
      was 89%. The corresponding specificities were 100%, 87% and 99%. The qPCR showed
      a linear increasing DNA copy number with increasing colour-changing units.
      Although slightly less sensitive than culture, this multiplex qPCR assay
      detecting U. urealyticum and U. parvum constitutes a simple and fast alternative
      to the traditional methods for identification of ureaplasmas and allows
      simultaneous species differentiation and quantitation in clinical samples.
      Furthermore, specimens overgrown by other bacteria using the culture method can
      be evaluated in the qPCR. 

PMID- 25047038
TI  - A randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on
      pruritus induced by histamine, and cowhage challenge in healthy volunteers.
AB  - BACKGROUND: Transient receptor potential vanilloid type 1 (TRPV1) is a non
      selective cation channel widely expressed in skin tissues, and peripheral sensory
      nerve fibres. Activation of TRPV1 releases neuropeptides; the resulting
      neurogenic inflammation is believed to contribute to the development of pruritus.
      A TRPV1 antagonist has the potential to perform as an anti-pruritic agent.
      SB705498 is a TRPV1 antagonist that has demonstrated in vitro activity against
      cloned TRPV1 human receptors and when orally administered has demonstrated
      pharmacodynamic activity in animal models and clinical studies. OBJECTIVES: To
      select a topical dose of SB705498 using the TRPV1 agonist capsaicin; to confirm
      engagement of the TRPV1 antagonistic action of SB705498 and assess whether the
      dose selected has an effect on itch induced by two challenge agents. METHODS: A
      clinical study was conducted in 16 healthy volunteers to assess the effects of 3
      doses of SB705498 on skin flare induced by capsaicin. Subjects with a robust
      capsaicin response were chosen to determine if the selected topical formulation
      of SB705498 had an effect on challenge agent induced itch. RESULTS: Following
      capsaicin challenge the greatest average reduction in area of flare was seen for
      the 3% formulation. This dose was selected for further investigation. Itch
      intensity induced by two challenge agents (cowhage and histamine) was assessed on
      the Computerised Visual Analogue Scale. The difference in average itch intensity
      (Weighted Mean Over 15 Mins) between the 3% dose of SB705498 and placebo for the
      cowhage challenge was -0.64, whilst the histamine challenge showed on average a 
      4.65 point change. CONCLUSIONS: The 3% topical formulation of SB705498 cream was
      clinically well tolerated and had target specific pharmacodynamic activity.
      However there were no clinically significant differences on pruritus induced by
      either challenge agent in comparison to placebo. SB705498 is unlikely to be of
      symptomatic benefit for histaminergic or non-histaminergic induced itch. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01673529.

PMID- 25047039
TI  - A rapid lateral flow immunoassay for the detection of tyrosine phosphatase-like
      protein IA-2 autoantibodies in human serum.
AB  - Type 1 diabetes (T1D) results from the destruction of pancreatic insulin
      producing beta cells and is strongly associated with the presence of islet
      autoantibodies. Autoantibodies to tyrosine phosphatase-like protein IA-2 (IA-2As)
      are considered to be highly predictive markers of T1D. We developed a novel
      lateral flow immunoassay (LFIA) based on a bridging format for the rapid
      detection of IA-2As in human serum samples. In this assay, one site of the IA-2As
      is bound to HA-tagged-IA-2, which is subsequently captured on the anti-HA-Tag
      antibody-coated test line on the strip. The other site of the IA-2As is bound to
      biotinylated IA-2, allowing the complex to be visualized using colloidal gold
      nanoparticle-conjugated streptavidin. For this study, 35 serum samples from T1D
      patients and 44 control sera from non-diabetic individuals were analyzed with our
      novel assay and the results were correlated with two IA-2A ELISAs. Among the 35
      serum samples from T1D patients, the IA-2A LFIA, the in-house IA-2A ELISA and the
      commercial IA-2A ELISA identified as positive 21, 29 and 30 IA-2A-positive sera,
      respectively. The major advantages of the IA-2A LFIA are its rapidity and
      simplicity. 

PMID- 25047040
TI  - Mild traumatic brain injury and ADHD: a systematic review of the literature and
      meta-analysis.
AB  - OBJECTIVE: This study investigated the association between mild traumatic brain
      injury (mTBI) and ADHD, which increases risk of injuries and accidents. METHOD:
      We conducted a systematic review and meta-analysis of studies that examined the
      relationship between mTBI and ADHD. RESULTS: Five studies, comprising 3,023 mTBI
      patients and 9,716 controls, fit our a priori inclusion and exclusion criteria. A
      meta-analysis found a significant association between ADHD and mTBI, which was
      significant when limited to studies that reported on ADHD subsequent to mTBI and
      when the direction of the association was not specified, but not for studies that
      reported mTBI subsequent to ADHD. Heterogeneity of effect size and publication
      biases were not evident. CONCLUSION: The literature documents a significant
      association between mTBI and ADHD. Further clarification of the relationship and
      direction of effect between mTBI and ADHD and treatment implications could have
      large clinical, scientific, and public health implications.

PMID- 25047041
TI  - Patients are blamed unfairly for pressure on emergency departments, consumer
      watchdog says.

PMID- 25047042
TI  - Pulmonary hypertension is related to peripheral endothelial dysfunction in heart
      failure with preserved ejection fraction.
AB  - BACKGROUND: Pulmonary hypertension (PH) and collagen metabolism abnormalities are
      prevalent in patients with heart failure with preserved ejection fraction
      (HFpEF). Peripheral endothelial dysfunction (PED) has been described in HF and in
      pulmonary arterial hypertension. Our aim is to determine whether PH is associated
      with PED and impaired collagen metabolism in patients with HFpEF.; METHODS AND
      RESULTS: Flow-mediated dilation of the brachial artery, matrix metalloproteinase
      2 and matrix metalloproteinase-9, tissue metalloproteinase inhibitor 1, and C
      terminal propeptide of type I procollagen were determined in 28 patients with
      HFpEF and 42 hypertensive controls. Patients with systolic pulmonary artery
      pressure >35 mm Hg on echocardiogram underwent a right heart catheterization.
      Patients with HFpEF had more severe PED than controls: flow-mediated dilation
      1.95% (-0.81 to 4.92) versus 5.02% (3.90 to 10.12), P=0.002. Twenty patients with
      PH underwent right heart catheterization: mean pulmonary artery pressure 38 (27
      52) mm Hg, wedge capillary pressure 18 (16-22) mm Hg, pulmonary vascular
      resistance 362 (235-603) dyn s cm(-5). There was a significant inverse
      correlation between flow-mediated dilation and pulmonary vascular resistance in
      patients with HFpEF and PH (r=-0.679; P=0.002). Patients with HFpEF showed higher
      matrix metalloproteinase-2 and C-terminal propeptide of type I procollagen values
      than hypertensive controls. Patients with HFpEF and higher C-terminal propeptide
      of type I procollagen values also had higher mean pulmonary artery pressure
      (r=0.553; P=0.014), transpulmonary gradient (r=0.560; P=0.013), and pulmonary
      vascular resistance (r=0.626; P=0.004). CONCLUSIONS: In patients with HFpEF,
      there is a significant correlation between PED and pulmonary vascular resistance.
      Collagen metabolism was more impaired in patients with HFpEF and PH. PED and
      collagen metabolism assessment could be useful tools to identify patients with
      HFpEF at risk of developing PH.

PMID- 25047043
TI  - Regulation of COX-2 expression by miR-146a in lung cancer cells.
AB  - Prostaglandins are a class of molecules that mediate cellular inflammatory
      responses and control cell growth. The oxidative conversion of arachidonic acid
      to prostaglandin H2 is carried out by two isozymes of cyclooxygenase, COX-1 and
      COX-2. COX-1 is constitutively expressed, while COX-2 can be transiently induced
      by external stimuli, such as pro-inflammatory cytokines. Interestingly, COX-2 is
      overexpressed in numerous cancers, including lung cancer. MicroRNAs (miRNAs) are
      small RNA molecules that function to regulate gene expression. Previous studies
      have implicated an important role for miRNAs in human cancer. We demonstrate here
      that miR-146a expression levels are significantly lower in lung cancer cells as
      compared with normal lung cells. Conversely, lung cancer cells have higher levels
      of COX-2 protein and mRNA expression. Introduction of miR-146a can specifically
      ablate COX-2 protein and the biological activity of COX-2 as measured by
      prostaglandin production. The regulation of COX-2 by miR-146a is mediated through
      a single miRNA-binding site present in the 3' UTR. Therefore, we propose that
      decreased miR-146a expression contributes to the up-regulation and overexpression
      of COX-2 in lung cancer cells. Since potential miRNA-mediated regulation is a
      functional consequence of alternative polyadenylation site choice, understanding
      the molecular mechanisms that regulate COX-2 mRNA alternative polyadenylation and
      miRNA targeting will give us key insights into how COX-2 expression is involved
      in the development of a metastatic condition. 

PMID- 25047044
TI  - Is the standard dose of amoxicillin-clavulanic acid sufficient?
AB  - BACKGROUND: The pharmacodynamic (PD) efficacy target of amoxicillin is 40% time
      above the minimal inhibition concentration (40%T > MIC). Recent studies of other
      antibiotics have shown that PD-efficacy targets are not always reached. The aim
      of this study was to evaluate the percentage of hospitalised patients, using
      amoxicillin/clavulanic acid intravenously (iv), that reach the pharmacodynamic
      efficacy target 40%T > MIC. Additionally, the association of demographic
      anthropomorphic and clinical parameters with the pharmacokinetics and
      pharmacodynamics of amoxicillin were determined. METHODS: In serum of 57
      hospitalised patients amoxicillin concentrations were measured using high
      performance liquid chromatography. Patients were older than 18 years and most
      patients had an abdominal infection. The standard amoxicillin/clavulanic acid
      dose was 4 times a day 1000/200 mg iv. Pharmacokinetic parameters were calculated
      with maximum a posteriori Bayesian estimation (MW?Pharm 3.60). A one-compartment
      open model was used. Individual dosing simulations were performed with MW?Pharm.
      RESULTS: In our study population, the mean (+/-SD) age was 67 (+/-16) years and
      the mean clearance corrected for bodyweight was 0.17 (+/-0.07) L/h/kg. Only, 65%
      of the patients reached the proposed amoxicillin 40%T > MIC with
      amoxicillin/clavulanic acid for bacterial MICs of 8 mg/L. A computer simulated
      increase of the standard dose to 6 times daily, increased this percentage to 95%.
      In this small study group 40%T > MIC was not associated with clinical or
      microbiological cure. CONCLUSION: A substantial proportion of the hospitalised
      patients did not reach the 40%T > MIC with the standard dose
      amoxicillin/clavulanic acid for a bacterial MIC of 8 mg/L. Therefore, we suggest
      increasing the standard dose of amoxicillin/clavulanic acid to 6 times a day in
      patients with severe Enterobacteriaceae infections. TRIAL REGISTRATION:  TRIAL
      REGISTRATION NUMBER: NTR1725 16th march 2009.

PMID- 25047045
TI  - IGF-1 enhances cell proliferation and survival during early differentiation of
      mesenchymal stem cells to neural progenitor-like cells.
AB  - BACKGROUND: There has been increasing interest recently in the plasticity of
      mesenchymal stem cells (MSCs) and their potential to differentiate into neural
      lineages. To unravel the roles and effects of different growth factors in the
      differentiation of MSCs into neural lineages, we have differentiated MSCs into
      neural lineages using different combinations of growth factors. Based on previous
      studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell
      isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation
      and reduce apoptosis in neural progenitor-like cells (NPCs) during
      differentiation of MSCs into NCPs.We induced MSCs differentiation under four
      different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1,
      (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a
      negative control. The neurospheres formed were characterized by
      immunofluorescence staining against nestin, and the expression was measured by
      flow cytometry. Cell proliferation and apoptosis were also studied by MTS and
      Annexin V assay, respectively, at three different time intervals (24 hr, 3 days,
      and 5 days). The neurospheres formed in the four groups were then terminally
      differentiated into neuron and glial cells. RESULTS: The four derived NPCs showed
      a significantly higher expression of nestin than was shown by the negative
      control. Among the groups treated with growth factors, NPCs treated with IGF-1
      showed the highest expression of nestin. Furthermore, NPCs derived using IGF-1
      exhibited the highest cell proliferation and cell survival among the treated
      groups. The NPCs derived from IGF-1 treatment also resulted in a better yield
      after the terminal differentiation into neurons and glial cells than that of the
      other treated groups. CONCLUSIONS: Our results suggested that IGF-1 has a crucial
      role in the differentiation of MSCs into neuronal lineage by enhancing the
      proliferation and reducing the apoptosis in the NPCs. This information will be
      beneficial in the long run for improving both cell-based and cell-free therapy
      for neurodegenerative diseases.

PMID- 25047046
TI  - Acupuncture for post anaesthetic recovery and postoperative pain: study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: We report on the design and implementation of a study protocol
      entitled Acupuncture randomised trial for post anaesthetic recovery and
      postoperative pain - a pilot study (ACUARP) designed to investigate the
      effectiveness of acupuncture therapy performed in the perioperative period on
      post anaesthetic recovery and postoperative pain. METHODS/DESIGN: The study is
      designed as a randomised controlled pilot trial with three arms and partial
      double blinding. We will compare (a) press needle acupuncture, (b) no treatment
      and (c) press plaster acupressure in a standardised anaesthetic setting. Seventy
      five patients scheduled for laparoscopic surgery to the uterus or ovaries will be
      allocated randomly to one of the three trial arms. The total observation period
      will begin one day before surgery and end on the second postoperative day. Twelve
      press needles and press plasters are to be administered preoperatively at seven
      acupuncture points. The primary outcome measure will be time from extubation to
      'ready for discharge' from the post anaesthesia care unit (in minutes). The
      'ready for discharge' end point will be assessed using three different scores:
      the Aldrete score, the Post Anaesthetic Discharge Scoring System and an In-House
      score. Secondary outcome measures will comprise pre-, intra- and postoperative
      variables (which are anxiety, pain, nausea and vomiting, concomitant medication).
      DISCUSSION: The results of this study will provide information on whether
      acupuncture may improve patient post anaesthetic recovery. Comparing acupuncture
      with acupressure will provide insight into potential therapeutic differences
      between invasive and non-invasive acupuncture techniques. TRIAL REGISTRATION:
      NCT01816386 (First received: 28 October 2012).

PMID- 25047047
TI  - Antioxidant activities of Lampaya medicinalis extracts and their main chemical
      constituents.
AB  - BACKGROUND: Lampaya medicinalis Phil. (Verbenaceae) is a plant used by Aymara and
      Quechua ethnic groups from Northern Chile as folk medicine in the treatment and
      cure of various diseases. The aim of this study was to investigate the in vitro
      antioxidant activity, total phenols content, total flavonoids content, total
      antioxidant activity, reducing power, brine shrimp cytotoxicity and identify the
      principal chemical constituents. METHODS: The crude hydroethanolic extract (HEE)
      and its partitioned fraction: hexane (HF), dichloromethane (DF), ethyl acetate
      (EAF), n-butanol (BF) and soluble residual aqueous fraction (RWF) were evaluated
      for their antioxidant activity using different assays namely, DPPH, ABTS, FRAP,
      beta-carotene bleaching assay. The content of total phenolics and total
      flavonoids were measured by Folin-Ciocalteau and by the AlCl3 colorimetric
      method, respectively. Reducing power was determined by phosphomolybdate and
      hexacyanoferrate (III) methods. Biotoxicity assays were performed on shrimps of
      Artemia salina. The EAF was fractionated using chromatographic methods. RESULTS:
      Considerable amount of phenolic and flavonoid contents were recorded in the
      hydroethanolic extract (HEE) and its derived fractions. Although HEE and all its
      derived fractions exhibited good antioxidant activities, the most distinguished
      radical scavenging potential was observed for ethyl acetate fraction (EAF). EAF
      showed the higher radical scavenging activity by DPPH (95%) and by ABTS (98%),
      antioxidant activity by FRAP (158.18 +/- 5.79 mg equivalent Trolox/g fraction),
      beta-carotene bleaching assay (86.8%), the highest total phenols content (101.26
      +/- 1.07 mg GAE/g fraction), the highest total flavonoids content (66.26 +/- 3.31
      MUg quercetin/g fraction). The EAF extract showed an reducing power of 78% and
      65% using the phosphomolybdate and hexacyanoferrate (III) assays,
      respectively.Four flavonoids, two p-hydroxyacetophenone derivatives and one
      iridoid were isolated from Lampaya medicinalis for the first time. CONCLUSION:
      EtOAc soluble fraction (EAF) shows the strongest antioxidant activity, and it can
      be attributed to its high content in phenolic and flavonoid compounds. It can be
      concluded that L.medicinalis can be used as an effective natural source of
      antioxidant, as ethnomedicine and as a commercial basis for the development of
      nutraceuticals.

PMID- 25047049
TI  - Morning handover of on-call issues: opportunities for improvement.
AB  - IMPORTANCE: Handover is the process of transferring pertinent patient information
      and clinical responsibility between health care practitioners. Few studies have
      examined morning handover from the overnight trainee to the daytime team.
      OBJECTIVE: To characterize current morning handover practices in 2 academic
      medical centers by assessing the frequency of omissions of clinically important
      overnight issues during morning handover and identifying factors that influence
      the occurrence of such omissions. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective, point-prevalence study was conducted in the general internal
      medicine wards of 2 tertiary care academic medical centers in Toronto, Ontario,
      Canada, in 2012 and 2013. Participants included on-call third-year medical
      students and first- and second-year residents. MAIN OUTCOMES AND MEASURES:
      Completeness of morning handover of clinically important overnight issues
      identified using a targeted medical records review and processes of morning
      handover characterized by direct observation. RESULTS: We identified 141
      clinically important overnight issues during 26 days of observation. The on-call
      trainee omitted 40.4% (95% CI, 32.3%-48.5%) of clinically important issues during
      morning handover and did not document any information in the patient's medical
      record for 85.8% (95% CI 80.1%-91.6%) of these issues. By univariate analysis,
      running the list patient-by-patient (ie, the entire team discusses each patient)
      (OR, 4.32; 95% CI, 1.94-9.60; P < .001) and using a dedicated handover location
      (OR, 2.61; 95% CI, 1.30-5.22; P = .007) positively correlated with handover of an
      issue taking place, whereas distractions in the meeting area inversely correlated
      with the likelihood of handover of an issue taking place (OR, 0.96 for every
      increase in 1 distraction; 95% CI, 0.93-0.98; P = .002). Using a multivariate
      mixed-effects model, only running the list remained as an independent predictor
      of the handover of an issue (OR, 3.80; 95% CI, 1.25-11.49; P = .02). CONCLUSIONS
      AND RELEVANCE: On-call trainees omit numerous clinically important issues when
      handing over to the daytime team. Training programs should introduce educational
      activities and workflow changes, and provide dedicated time and a distraction
      free environment, to improve handover of on-call issues.

PMID- 25047050
TI  - Theory of plasma confinement in non-axisymmetric magnetic fields.
AB  - The theory of plasma confinement by non-axisymmetric magnetic fields is reviewed.
      Such fields are used to confine fusion plasmas in stellarators, where in contrast
      to tokamaks and reversed-field pinches the magnetic field generally does not
      possess any continuous symmetry. The discussion is focussed on
      magnetohydrodynamic equilibrium conditions, collisionless particle orbits, and
      the kinetic theory of equilbrium and transport. Each of these topics is
      fundamentally affected by the absence of symmetry in the magnetic field: the
      field lines need not trace out nested flux surfaces, the particle orbits may not
      be confined, and the cross-field transport can be very large. Nevertheless, by
      tailoring the magnetic field appropriately, well-behaved equilibria with good
      confinement can be constructed, potentially offering an attractive route to
      magnetic fusion. In this article, the mathematical apparatus to describe
      stellarator plasmas is developed from first principles and basic elements
      underlying confinement optimization are introduced. 

PMID- 25047048
TI  - Depletion of 14-3-3gamma reduces the surface expression of Transient Receptor
      Potential Melastatin 4b (TRPM4b) channels and attenuates TRPM4b-mediated
      glutamate-induced neuronal cell death.
AB  - BACKGROUND: TRPM4 channels are Ca2+-activated nonselective cation channels which
      are deeply involved in physiological and pathological conditions. However, their
      trafficking mechanism and binding partners are still elusive. RESULTS: We have
      found the 14-3-3gamma as a binding partner for TRPM4b using its N-terminal
      fragment from the yeast-two hybrid screening. Ser88 at the N-terminus of TRPM4b
      is critical for 14-3-3gamma binding by showing GST pull-down and co
      immunoprecipitation. Heterologous overexpression of 14-3-3gamma in HEK293T cells
      increased TRPM4b expression on the plasma membrane which was measured by whole
      cell recordings and cell surface biotinylation experiment. Surface expression of
      TRPM4b was greatly reduced by short hairpin RNA (shRNA) against 14-3-3gamma.
      Next, endogenous TRPM4b-mediated currents were electrophysiologically
      characterized by application of glutamate and 9-phenanthrol, a TRPM4b specific
      antagonist in HT-22 cells which originated from mouse hippocampal neurons.
      Glutamate-induced TRPM4b currents were significantly attenuated by shRNAs against
      14-3-3gamma or TRPM4b in these cells. Finally, glutamate-induced cell death was
      greatly prevented by treatment of 9-phenanthrol or 14-3-3gamma shRNA. CONCLUSION:
      These results showed that the cell surface expression of TRPM4 channels is
      mediated by 14-3-3gamma binding, and the specific inhibition of this trafficking
      process can be a potential therapeutic target for glutamate-induced neuronal cell
      death.

PMID- 25047052
TI  - Response to 'Preserved corticospinal conduction without voluntary movement after
      spinal cord injury'.

PMID- 25047051
TI  - Are oxybutynin and trospium efficacious in the treatment of detrusor overactivity
      in spinal cord injury patients?
AB  - OBJECTIVES: To evaluate the efficacy of anticholinergic agents in the treatment
      of neurogenic overactive bladder (NOAB) and neurogenic detrusor overactivity
      (NDO) in spinal cord injury (SCI) patients on clean intermittent catheterisation
      (CIC). METHODS: Chronic suprasacral SCI patients on CIC presenting with at least
      one urinary leakage a day were included. Urodynamics and voiding diaries were
      performed at baseline and 1 month follow-up. In case of NDO at baseline, an
      anticholinergic drug was prescribed. RESULTS: The 231 SCI patients presented with
      one to five urinary leakages per day (mean 2.1). Urodynamics showed NDO in all
      patients. A new anticholinergic treatment was started in all, either in
      monotherapy (134 patients) or in association with the existing anticholinergic
      drug (oxybutynin+trospium bitherapy, 97 patients). The mean maximum bladder
      capacity significantly increased from 225 to 441 ml, and the mean involuntary
      detrusor contractions (IDC) significantly decreased from 67 to 41 cm H2O. Only 75
      SCI patients (32%) were fully continent. However, 25 out of these 75 patients
      showed persistent NDO, with amplitudes of IDC above 40 cm H2O in 12 patients.
      Incontinence was still found in 156 SCI patients (67%), with an average of 1,2
      leakages a day. In 100 patients, amplitudes of IDC remained above 40 cm H2O.
      There was no statistical difference between patients on anticholinergic
      monotherapy or bitherapy at follow-up. CONCLUSION: Anticholinergic treatment is
      not always satisfactory in terms of control of NDO and rarely allows full
      continence. Urodynamic follow-up is mandatory in all patients, even in those
      showing clinical continence.

PMID- 25047053
TI  - Effects of methylprednisolone and 4-chloro-3-hydroxyanthranilic acid in
      experimental spinal cord injury in the guinea pig appear to be mediated by
      different and potentially complementary mechanisms.
AB  - STUDY DESIGN: Blinded, placebo-controlled, parallel treatment group studies of
      the effects of methylprednisolone (MP) or 4-chloro-3-hydroxyanthranilate (4-Cl-3
      HAA) on behavioral outcome and quinolinic acid tissue levels from experimental
      thoracic spinal cord injury in adult guinea pigs. OBJECTIVES: To compare the
      effects of treatment with high-dose MP, a corticosteroid, and 4-Cl-3-HAA, a
      compound that inhibits synthesis of the neurotoxin quinolinic acid (QUIN) by
      activated macrophages. To explore the effect of different times of treatment
      using these two approaches to ameliorating secondary tissue damage. SETTING:
      Laboratory animal studies at the University of North Carolina, Chapel Hill, NC,
      USA. METHODS: Standardized spinal cord injuries were produced in anesthetized
      guinea pigs, using lateral compression of the spinal cord. Behavioral impairment
      and recovery were measured by placing and toe-spread responses (motor function),
      cutaneus trunci muscle reflex receptive field areas and somatosensory-evoked
      potentials (sensory function). Tissue quinolinic acid levels were measured by gas
      chromatograph/mass spectrometry. RESULTS: The current experiments showed a
      reduction in delayed loss of motor and sensory function in the guinea pig with MP
      (150 mg kg(-1), intraperitoneally in split doses between 0.5 and 6 h), but no
      significant reduction in tissue QUIN. Improved sensory function was seen with a
      single dose of 60 mg kg(-1) MP intraperitoneally at 5 h after injury, but not at
      10 h after injury. A single dose of 4-Cl-3-HAA at 5 h in the guinea pig did not
      produce the sensory and motor improvements seen in previous studies with 12 days
      of dosing, beginning at 5 h. CONCLUSION: These studies, together with earlier
      findings, indicate that both drugs can attenuate secondary pathologic damage
      after SCI, but through separate mechanisms. These are most likely an acute
      reduction by MP of oxidative processes and reduction by 4-Cl-3-HAA of QUIN
      synthesis.

PMID- 25047054
TI  - TENS augments blood flow in somatotopically linked spinal cord segments and
      mitigates compressive ischemia.
AB  - STUDY DESIGN: This was an acute basic physiological study in anesthetized adult
      male rats. OBJECTIVES: The purpose of this study was to determine, in an animal
      model, whether innocuous somatic stimulation, in the form of transcutaneous
      electrical nerve stimulation (TENS), could produce a sustained augmentation of
      spinal cord blood flow, and whether this effect was robust in the face of
      relatively mild, non-destructive compression of the spinal cord. SETTING:
      Neurophysiology laboratory, Canadian Memorial Chiropractic College, Toronto,
      Canada. METHODS: In anesthetized adult male Wistar rats, spinal cord blood flow
      was measured with laser Doppler flowmetry during 5- and 15-min epochs of TENS
      stimulation in uncompressed and compressed lumbar spinal cord. RESULTS: TENS
      applied to the L4/L5 dermatomes was associated with augmentation of blood flow in
      somatotopically linked spinal cord segments. This augmentation was robust in the
      face of non-destructive compression of the spinal cord, was sustained for periods
      of stimulation up to 15 min and occurred in the absence of any change in the mean
      arterial blood pressure. CONCLUSIONS: TENS augments spinal cord blood flow in the
      uncompressed spinal cord and during acute, non-destructive spinal cord
      compression. It remains to be seen whether similar results can be achieved in
      chronically compressed spinal cord and spinal nerve roots, and whether these
      results have clinical implications in human syndromes of spinal cord compression.

PMID- 25047055
TI  - Reply: evidence against volume conduction to explain normal MEPs in muscles with
      low motor power in SCI.

PMID- 25047056
TI  - In vitro dissolution study of acetylsalicylic acid solid dispersions. Tunable
      drug release allowed by the choice of polymer matrix.
AB  - Abstract Due to their high versatility and diverse excipient options, solid
      dispersions (SDs) are an elegant choice for the formulation of active
      pharmaceutical ingredients with inconvenient solubility. Four distinct types of
      polymers with different physicochemical properties [polyvinylpyrrolidone, poly[N
      (2-hydroxypropyl)-metacrylamide], poly(2-ethyl-2-oxazoline), and polyethylene
      glycol] and variable molecular weights were compared to investigate the influence
      of the polymer matrix on drug release. To probe the extent of intercomponent
      interactions, acetylsalicylic acid (ASA) was used as a model active substance.
      Controlled drug release was demonstrated for all four types of polymer-ASA SDs
      created by the freeze-drying method. While the polyethylene glycol-ASA SD
      exhibited an increased dissolution rate, the other polymer-ASA systems exhibited
      significantly reduced drug dissolution kinetics compared to free ASA.
      Furthermore, in contrast to physical mixtures, the prepared SDs all exhibited
      zero-order dissolution kinetics for ASA. The dissolution rate was strongly
      dependent on the molecular weight of the polymer. These results demonstrate that
      the type of SD may be controlled by the chemical constitutions of the polymers
      and that appropriate selection of the molecular weight of the polymer matrix
      enables finely tuned drug release over a wide range of dissolution rates.

PMID- 25047057
TI  - Physicochemical stability of a new topical timolol 0.5% gel formulation for the
      treatment of infant hemangioma.
AB  - Infant hemangioma (IH) is the most common tumor in infants, which affects 5-10%
      of white children. It is a tumor of vascular origin that appears in the first
      months of life. The indication for the treatment of the IH is not approved in the
      datasheet of the product, however it has been used in the infant hemangioma by
      topical administration as an alternative to oral propranolol, avoiding the main
      problems of the oral route (bradycardia and hypotension). The objective of this
      work is to study the physical and chemical (HPLC stability indicating method)
      stability of a 0.5% timolol gel for topical application during 60 days
      (considering the stability limit as 90% of initial concentration of timolol
      maleate). The gel was prepared with a polyacrylic acid derivative and the
      physical stability of the system was studied by visual control, rheological and
      mechanical characterization. The studied formulation guarantees the correct dose
      administering and stability after 60 days stored at 25 +/- 2  degrees C and light
      protected (tube of aluminum). We have developed an easy topical gel for the
      treatment of infant hemangioma with physical and chemical stability higher than
      those provided by the majority of hospitals. 

PMID- 25047058
TI  - Extracellular matrix regulation in the muscle satellite cell niche.
AB  - Increasing evidence points to extracellular matrix (ECM) components playing
      integral roles in regulating the muscle satellite cell (SC) niche. Even small
      alterations to the niche ECM can have profound effects on SC localization,
      activation, self-renewal, proliferation and differentiation. This review will
      focus on the ECM components that comprise the niche, how they are modulated in
      health and disease and how these changes are thought to affect SC function.
      Particular emphasis will be placed on the pathological niche and interventions
      that aim to restore healthy structure and function, as a better understanding of
      the interplay between the SC and its environment will drive more targeted and
      effective therapies.

PMID- 25047059
TI  - Highly mesoporous metal-organic framework assembled in a switchable solvent.
AB  - The mesoporous metal-organic frameworks are a family of materials that have pore
      sizes ranging from 2 to 50 nm, which have shown promising applications in
      catalysis, adsorption, chemical sensing and so on. The preparation of mesoporous
      metal-organic frameworks usually needs the supramolecular or cooperative template
      strategy. Here we report the template-free assembly of mesoporous metal-organic
      frameworks by using CO2-expanded liquids as switchable solvents. The mesocellular
      metal-organic frameworks with large mesopores (13-23 nm) are formed, and their
      porosity properties can be easily adjusted by controlling CO2 pressure. Moreover,
      the use of CO2 can accelerate the reaction for metal-organic framework formation
      from metal salt and organic linker due to the viscosity-lowering effect of CO2,
      and the product can be recovered through CO2 extraction. The as-synthesized
      mesocellular metal-organic frameworks are highly active in catalysing the aerobic
      oxidation of benzylic alcohols under mild temperature at atmospheric pressure.

PMID- 25047060
TI  - High-performance n-channel organic thin-film transistor based on naphthalene
      diimide.
AB  - A conjugated molecule comprising 1,4,5,8-naphthalene diimide (NDI) substituted
      with two octadecylamine (OD) chains has been synthesized (NDI-OD2) in a single
      step from commercial materials, and its organic thin-film transistor (OTFT)
      devices on glass substrate have been studied using poly(vinyl alcohol) (PVA) gate
      dielectric material. Although we utilized the PVA dielectric without any
      intermediate buffer layer or PVA cross-linkers, excellent electron mobility as
      high as ~1.0 cm(2)V(-1) s(-1) are obtained. This NDI-OD2 molecule exhibits
      comparable optical (Eg(UV) ~3.1 eV) and electrochemical band gaps (Eg(CV) ~3.02
      eV) with a lowest unoccupied molecular orbital (LUMO) energy levels of ~3.3 eV.
      When processed by solution method, this material forms rod-shaped crystalline
      microstructures, whereas, when thermally deposited, it assumes the formation of
      smooth 2D films. The chemical as well as physical properties and theoretical
      calculations of NDI-OD2 have been studied and the effect of the C-18 alkyl chain
      unit has been discussed. The OTFT consisting of NDI-OD2 exhibits excellent
      performance parameters such as high electron mobility (MUe) and Ion-to-Ioff
      ratio. After demonstrating the high performance of NDI-OD2-based TFT devices
      fabricated with biocompatible PVA dielectric, we have also demonstrated that
      these devices can be degraded because of the presence of this PVA dielectric when
      exposed to a high-moisture environment. The systematic degradation of the device
      activity in a controlled way within 10 days of exposure (>80% moisture) is also
      presented here. In this study, a conceptually important feature and futuristic
      aspect that the n-channel TFT devices can also be biodegraded irreversibly is
      demonstrated. This concept of developing a low cost and biodegradable OTFT device
      with biocompatible PVA dielectric with excellent electron mobility is expected to
      have diverse applications in disposable electronic tags, biomedical devices, and
      food industry packing. 

PMID- 25047061
TI  - Personalized prostate cancer screening among men with high risk genetic
      predisposition- study protocol for a prospective cohort study.
AB  - BACKGROUND: Prostate cancer screening among the general population is highly
      debatable. Nevertheless, screening among high-risk groups is appealing. Prior
      data suggests that men carrying mutations in the BRCA1& 2 genes may be at
      increased risk of developing prostate cancer. Additionally, they appear to
      develop prostate cancer at a younger age and with a more aggressive course.
      However, prior studies did not systematically perform prostate biopsies and thus
      cannot determine the true prevalence of prostate cancer in this population.
      METHODS: This will be a prospective diagnostic trial of screening for prostate
      cancer among men with genetic predisposition. The target population is males (40
      70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be
      identified via our Genetic counseling unit. All men after signing an informed
      consent will undergo the following tests: PSA, free to total PSA, MRI of prostate
      and prostate biopsy. The primary endpoint will be to estimate the prevalence,
      stage and grade of prostate cancer in this population. Additionally, the study
      aims to estimate the impact of these germ line mutations on benign prostatic
      hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine
      and serum of this unique cohort for future investigations. Finally, this study
      will identify an inception cohort for future interventional studies of primary
      and secondary prevention. DISCUSSION: The proposed research is highly
      translational and focuses not only on the clinical results, but on the future
      specimens that will be used to advance our understanding of prostate cancer patho
      physiology. Most importantly, these high-risk germ-line mutation carriers are
      ideal candidates for primary and secondary prevention initiatives. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02053805.

PMID- 25047062
TI  - Olefin metathesis reactions with fluorinated substrates, catalysts, and solvents.

PMID- 25047064
TI  - Outcome of conjunctival flap repair for corneal defects with and without an
      acellular submucosa implant in 73 canine eyes.
AB  - OBJECTIVE: To report and compare the success rate of a conjunctival pedicle flap
      (CPF) alone vs. a CPF with an underlying acellular submucosa implant for the
      repair of deep or perforating corneal wounds in dogs. PROCEDURES: Records of 69
      dogs (73 eyes) receiving a CPF with or without an acellular submucosa implant
      between 2004 and 2012 were reviewed. Successful outcome was defined as a
      comfortable eye with vision at the last post-operative evaluation. Age, breed,
      underlying corneal disease, surgical time, lesion characteristics, topical
      therapies, and postoperative complications were investigated. RESULTS: Groups
      consisted of dogs that had a CPF alone (n = 37) and dogs that had a CPF plus an
      acellular submucosa implant (n = 36). Age, lesion size, surgical time, and time
      to discontinuation of topical anti-proteolytic medications was not significant
      between groups. Topical antibiotic use was terminated 13 days sooner (P <= 0.01)
      in dogs with an acellular submucosa implant. The combined success rate of all
      corneal wounds was 93% with success rate of corneal perforations, descemetoceles,
      and deep stromal wounds being 89%, 95%, and 100%, respectively. There was no
      difference in overall success rate between groups. Increasing age was associated
      with a negative outcome (P <= 0.01). Lesion size, presence of a corneal
      perforation, and concurrent keratoconjunctivitis sicca was not associated with a
      negative outcome. CONCLUSIONS: A comparable success rate is achieved for deep or
      perforating corneal wounds stabilized with a CPF alone vs. a CPF plus acellular
      submucosa. Glaucoma, persistent uveitis, and cataract formation were not reported
      as post-operative complications in this study population.

PMID- 25047063
TI  - Changes in speckle tracking echocardiography measures of ventricular function
      after percutaneous implantation of the Edwards SAPIEN transcatheter heart valve
      in the pulmonary position.
AB  - BACKGROUND: Patients with free pulmonary regurgitation or mixed pulmonary
      stenosis and regurgitation and severely dilated right ventricles (RV) show little
      improvement in ventricular function after pulmonary valve replacement when
      assessed by traditional echocardiographic markers. We evaluated changes in right
      and left ventricular (LV) function using speckle tracking echocardiography in
      patients after SAPIEN transcatheter pulmonary valve (TPV) placement. METHODS:
      Echocardiograms were evaluated at baseline, discharge, 1 and 6 months after TPV
      placement in 24 patients from 4 centers. Speckle tracking measures of function
      included peak longitudinal strain, strain rate, and early diastolic strain rate.
      RV fractional area change, tricuspid annular plane systolic excursion, and left
      ventricular LV ejection fraction were assessed. Routine Doppler and tissue
      Doppler velocities were measured. RESULTS: At baseline, all patients demonstrated
      moderate to severe pulmonary regurgitation; this improved following TPV
      placement. No significant changes were detected in conventional measures of RV or
      LV function at 6 months. RV longitudinal strain (-16.9% vs. -19.6%, P < 0.01),
      strain rate (-0.87 s(-1) vs. -1.16 s(-1) , P = 0.01), and LV longitudinal strain
      (-16.2% vs. -18.2%, P = 0.01) improved between baseline and 6 month follow-up. RV
      early diastolic strain rate, LV longitudinal strain rate and early diastolic
      strain rate showed no change. CONCLUSION: Improvements in RV longitudinal strain,
      strain rate, and LV longitudinal strain are seen at 6 months post-TPV. Diastolic
      function does not appear to change at 6 months. Speckle tracking echocardiography
      may be more sensitive than traditional measures in detecting changes in systolic
      function after TPV implantation.

PMID- 25047065
TI  - Pulse oximetry screening of newborns: Not only a screening test for congenital
      heart disease.

PMID- 25047066
TI  - Epithelium-dependent profibrotic milieu in the pathogenesis of idiopathic
      pulmonary fibrosis: current status and future directions.
AB  - BACKGROUND AND AIM: Idiopathic pulmonary fibrosis (IPF) is characterized by
      hyperplasia of type II alveolar epithelial cells, aggregation of activated
      (myo)fibroblasts and excessive deposition of extracellular matrix, which will
      ultimately lead to lung architecture destruction with no proven effective
      therapies. Despite a significant increase in our understanding on the etiology
      and pathogenesis of IPF, the real triggers that initiate epithelial cell injury
      and promote fibrosis evolution are still elusive. We wanted to discuss the
      evolution of hypothesis on IPF pathogenesis and to suggest some new directions
      which need to be further elucidated. METHODS: We have done a literature search in
      PubMed database by using the term 'idiopathic pulmonary fibrosis' AND
      (pathogenesis OR inflammation OR wound healing OR apoptosis OR extracellular
      matrix OR animal model). RESULTS: Inflammatory hypothesis had been the dominant
      idea for several decades which suggests that chronic inflammation drives the
      onset and advance of the fibrotic process. However, it is seriously challenged
      nowadays because lung tissues from IPF patients exhibit little inflammatory
      lesions. Also, anti-inflammation therapy failed to exert a beneficial effect to
      IPF patients. Furthermore, experimental lung fibrosis can be realized independent
      of inflammation. Today, modern paradigm suggests that IPF is mainly driven by the
      profibtic milieu formed by epithelial injury/ disability and dysregulated
      epithelial mesenchymal interaction. CONCLUSIONS: Epithelium-dependent profibrotic
      milieu formation and mesenchymal activation is the current view on the
      pathogenesis of IPF. New evidence from more analogous animal models may emerge
      and shift our thinking to a new and more faithful concept in the future.

PMID- 25047067
TI  - Real-time three-dimensional imaging of epidermal splitting and removal by high
      definition optical coherence tomography.
AB  - While real-time 3-D evaluation of human skin constructs is needed, only 2-D non
      invasive imaging techniques are available. The aim of this paper is to evaluate
      the potential of high-definition optical coherence tomography (HD-OCT) for real
      time 3-D assessment of the epidermal splitting and decellularization. Human skin
      samples were incubated with four different agents: Dispase II, NaCl 1 M, sodium
      dodecyl sulphate (SDS) and Triton X-100. Epidermal splitting, dermo-epidermal
      junction, acellularity and 3-D architecture of dermal matrices were evaluated by
      High-definition optical coherence tomography before and after incubation. Real
      time 3-D HD-OCT assessment was compared with 2-D en face assessment by
      reflectance confocal microscopy (RCM). (Immuno) histopathology was used as
      control. HD-OCT imaging allowed real-time 3-D visualization of the impact of
      selected agents on epidermal splitting, dermo-epidermal junction, dermal
      architecture, vascular spaces and cellularity. RCM has a better resolution (1
      MUm) than HD-OCT (3 MUm), permitting differentiation of different collagen
      fibres, but HD-OCT imaging has deeper penetration (570 MUm) than RCM imaging (200
      MUm). Dispase II and NaCl treatments were found to be equally efficient in the
      removal of the epidermis from human split-thickness skin allografts. However, a
      different epidermal splitting level at the dermo-epidermal junction could be
      observed and confirmed by immunolabelling of collagen type IV and type VII.
      Epidermal splitting occurred at the level of the lamina densa with dispase II and
      above the lamina densa (in the lamina lucida) with NaCl. The 3-D architecture of
      dermal papillae and dermis was more affected by Dispase II on HD-OCT which
      corresponded with histopathologic (orcein staining) fragmentation of elastic
      fibres. With SDS treatment, the epidermal removal was incomplete as remnants of
      the epidermal basal cell layer remained attached to the basement membrane on the
      dermis. With Triton X-100 treatment, the epidermis was not removed. In
      conclusion, HD-OCT imaging permits real-time 3-D visualization of the impact of
      selected agents on human skin allografts. 

PMID- 25047068
TI  - Effect of sorghum flour addition on in vitro starch digestibility, cooking
      quality, and consumer acceptability of durum wheat pasta.
AB  - Whole grain sorghum is a valuable source of resistant starch and polyphenolic
      antioxidants and its addition into staple food like pasta may reduce the starch
      digestibility. However, incorporating nondurum wheat materials into pasta
      provides a challenge in terms of maintaining cooking quality and consumer
      acceptability. Pasta was prepared from 100% durum wheat semolina (DWS) as control
      or by replacing DWS with either wholegrain red sorghum flour (RSF) or white
      sorghum flour (WSF) each at 20%, 30%, and 40% incorporation levels, following a
      laboratory-scale procedure. Pasta samples were evaluated for proximate
      composition, in vitro starch digestibility, cooking quality, and consumer
      acceptability. The addition of both RSF and WSF lowered the extent of in vitro
      starch digestion at all substitution levels compared to the control pasta. The
      rapidly digestible starch was lowered in all the sorghum-containing pastas
      compared to the control pasta. Neither RSF or WSF addition affected the pasta
      quality attributes (water absorption, swelling index, dry matter, adhesiveness,
      cohesiveness, and springiness), except color and hardness which were negatively
      affected. Consumer sensory results indicated that pasta samples containing 20%
      and 30% RSF or WSF had acceptable palatability based on meeting one or both of
      the preset acceptability criteria. It is concluded that the addition of
      wholegrain sorghum flour to pasta at 30% incorporation level is possible to
      reduce starch digestibility, while maintaining adequate cooking quality and
      consumer acceptability. 

PMID- 25047069
TI  - Oral health-related quality of life of schoolchildren: impact of clinical and
      psychosocial variables.
AB  - BACKGROUND: Besides the clinical aspects, the patient's perspective of oral
      health-related quality of life (OHRQoL) may be influenced by a series of
      individual characteristics. AIM: The aim was to investigate the impact of
      clinical and psychosocial variables on the OHRQoL of Brazilian schoolchildren.
      DESIGN: A school-based cross-sectional study was conducted with children of 8-10
      year old attending public (15) and private (5) schools (n = 749). Questionnaires
      were applied to parents to obtain socioeconomic characteristics, and children
      were interviewed. Assessment of OHRQoL was performed using the Child Perceptions
      Questionnaire 8-10 (CPQ). Oral health examinations included periodontal
      condition, dental caries, dental trauma, and malocclusion assessment. Unadjusted
      analyses were undertaken using t-tests and one-way analysis of variance. Multiple
      linear regression was used to assess the effects of independent variables on CPQ
      scores. RESULTS: Factors associated with higher CPQ scores in the linear
      regression analysis after adjustments were family income, presence of decayed
      teeth, self-reported dental trauma, dental fear, and dental pain. CONCLUSION:
      Oral health-related quality of life was influenced by psychosocial and clinical
      variables.

PMID- 25047070
TI  - Mechanisms underlying the cytotoxicity of a novel quinazolinedione-based redox
      modulator, QD232, in pancreatic cancer cells.
AB  - BACKGROUND AND PURPOSE: Pancreatic cancer is characterized by alterations in
      several key signalling proteins, including increased expression and activity of
      the Src tyrosine kinase and focal adhesion kinase (FAK), which have been linked
      to its chemoresistance. Sustained Src inhibition reactivates survival pathways
      regulated by the transcription factor STAT3, also leading to resistance.
      Therefore, simultaneously targeting Src/FAK and STAT3 signalling could provide an
      important strategy for treating pancreatic cancer. Recently, we described novel
      quinazolinediones that increased generation of reactive oxygen species (ROS) and
      were cytotoxic in pancreatic cancer cells. Here, we have investigated effects of
      our lead compound, QD232, on Src/FAK and STAT3 signalling. EXPERIMENTAL APPROACH:
      The major signalling pathways affected by QD232 in pancreatic cancer cell lines
      were identified by Kinexus proteomic analysis. Changes in key signalling proteins
      were confirmed by Western blotting. Cell migration was assessed by Boyden chamber
      and wound healing assays. Direct inhibition of kinase activity in vitro was
      assayed with a panel of 92 oncogenic kinases. Safety and efficacy of QD232 were
      determined in a xenograft mouse model of pancreatic cancer. KEY RESULTS: QD232
      potently inhibited Src/FAK and STAT3 phosphorylation, decreasing pancreatic
      cancer cell viability and migration. Furthermore, QD232 arrested cell cycle
      progression and induced apoptosis in these cells at low micromolar
      concentrations. Effects of QD232 on Src/FAK and STAT3 phosphorylation were
      blocked by N-acetylcysteine or glutathione. CONCLUSIONS AND IMPLICATIONS: QD232
      is a novel compound with a unique, ROS-dependent mechanism, effective in drug
      resistant cancer cell lines. This compound shows potential as therapy for
      pancreatic cancer.

PMID- 25047071
TI  - Noble gas encapsulation: clathrate hydrates and their HF doped analogues.
AB  - The significance of clathrate hydrates lies in their ability to encapsulate a
      vast range of inert gases. Although the natural abundance of a few noble gases
      (Kr and Xe) is poor their hydrates are generally abundant. It has already been
      reported that HF doping enhances the stability of hydrogen hydrates and methane
      hydrates, which prompted us to perform a model study on helium, neon and argon
      hydrates with their HF doped analogues. For this purpose 5(12), 5(12)6(8) and
      their HF doped analogues are taken as the model clathrate hydrates, which are
      among the building blocks of sI, sII and sH types of clathrate hydrate crystals.
      We use the dispersion corrected and gradient corrected hybrid density functional
      theory for the calculation of thermodynamic parameters as well as conceptual
      density functional theory based reactivity descriptors. The method of the ab
      initio molecular dynamics (AIMD) simulation is used through atom centered density
      matrix propagation (ADMP) techniques to envisage the structural behaviour of
      different noble gas hydrates on a 500 fs timescale. Electron density analysis is
      carried out to understand the nature of Ng-OH2, Ng-FH and Ng-Ng interactions. The
      current results noticeably demonstrate that the noble gas (He, Ne, and Ar)
      encapsulation ability of 5(12), 5(12)6(8) and their HF doped analogues is
      thermodynamically favourable. 

PMID- 25047072
TI  - The potential for biodiversity offsetting to fund effective invasive species
      control.
AB  - Compensating for biodiversity losses in 1 location by conserving or restoring
      biodiversity elsewhere (i.e., biodiversity offsetting) is being used increasingly
      to compensate for biodiversity losses resulting from development. We considered
      whether a form of biodiversity offsetting, enhancement offsetting (i.e.,
      enhancing the quality of degraded natural habitats through intensive ecological
      management), can realistically secure additional funding to control biological
      invaders at a scale and duration that results in enhanced biodiversity outcomes.
      We suggest that biodiversity offsetting has the potential to enhance biodiversity
      values through funding of invasive species control, but it needs to meet 7 key
      conditions: be technically possible to reduce invasive species to levels that
      enhance native biodiversity; be affordable; be sufficiently large to compensate
      for the impact; be adaptable to accommodate new strategic and tactical
      developments while not compromising biodiversity outcomes; acknowledge
      uncertainties associated with managing pests; be based on an explicit risk
      assessment that identifies the cost of not achieving target outcomes; and include
      financial mechanisms to provide for in-perpetuity funding. The challenge then for
      conservation practitioners, advocates, and policy makers is to develop frameworks
      that allow for durable and effective partnerships with developers to realize the
      full potential of enhancement offsets, which will require a shift away from
      traditional preservation-focused approaches to biodiversity management.

PMID- 25047073
TI  - Kappa and lambda light chain mRNA in situ hybridization compared to flow
      cytometry and immunohistochemistry in B cell lymphomas.
AB  - BACKGROUND: Detection of B cell clonality is useful for assisting in the
      diagnosis of B cell lymphomas. Clonality assessment can be accomplished through
      evaluation of KAPPA and LAMBDA light chain expression. Currently, only slide
      based methods are available for the majority of patient biopsies and do not
      detect light chain protein or mRNA in many B-cell lymphomas. Herein we evaluated
      a new method, known as colorimetric in situ hybridization (CISH), with improved
      sensitivity and multiplexing capacity, for its usefulness in clonality detection
      in mature B cell malignancies. METHODS: The KAPPA and LAMBDA ISH was performed on
      a Ventana Benchmark XT utilizing two color chromogenetic detection. The probes
      comprised 2 haptenated riboprobes each approximately 500 base pairs long directed
      against the conserved regions of either KAPPA or LAMBDA mRNA. The dual colors
      consisted of silver deposition (black) for KAPPA light chain and a novel (pink)
      chromogen for LAMBDA light chain. Following optimization, CISH allowed
      visualization of mRNA in benign B cells in reactive tissues including germinal
      center, mantle zone, and post-germinal center cells. We then identified 79 cases
      of B cell lymphoma with formalin-fixed paraffin-embedded (FFPE) biopsies
      including: follicular (36 cases), mantle cell (6 cases), marginal zone (12
      cases), lymphoplasmacytic (6 cases), small lymphocytic (4 cases), and diffuse
      large B cell (15 cases), which were selected on the basis of either prior flow
      cytometry or immunohistochemistry (IHC) results to serve as the predicate, "gold
      standard," comparator. RESULTS: 39/79 (49.4%) cases were classified as KAPPA and
      29/79 (36.7%) as LAMBDA light chain restricted; while 9/79 (11.3%) cases were
      classified as indeterminate. Of the 70 cases with KAPPA or LAMBDA light chain
      restricted CISH, 69/70 (98.6%) were concordant with the reference method, while
      1/70 (1.4%) was discordant. CONCLUSIONS: Optimized CISH detected lower levels of
      mRNA than can be visualized with current slide based methods, making clonality
      assessment in FFPE biopsies possible for mature B cell neoplasms. In this
      preliminary study, CISH was highly accurate compared to flow cytometry or IHC.
      CISH offers the possibility of wider applicability of light chain ISH and is
      likely to become a useful diagnostic tool. VIRTUAL SLIDES: The virtual slide(s)
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1430491067123856.

PMID- 25047074
TI  - Cost analysis and exploratory cost-effectiveness of youth-friendly sexual and
      reproductive health services in the Republic of Moldova.
AB  - BACKGROUND: Youth-friendly sexual and reproductive health services (YFHS) have
      high priority in many countries. Yet, little is known about the cost and cost
      effectiveness of good quality YFHS in resource limited settings. This paper
      analyses retrospectively costs and potential cost-effectiveness of four well
      performing youth-friendly health centres (YFHC) in Moldova. This study assesses:
      (1) what were the costs of YFHSs at centre level, (2) how much would scaling-up
      to a national good quality YFHS programme cost, and (3) was the programme
      potentially cost-effective? METHODS: Four well performing YFHCs were selected for
      the study. YFHS costs were analysed per centre, funding source, service and
      person reached. The costing results were extrapolated to estimate cost of a good
      quality national YFHS programme in Moldova. A threshold analysis was carried out
      to estimate the required impact level for the YFHSs to break-even (become cost
      saving). RESULTS: Average annual cost of a well performing YFHC was USD 26,000 in
      2011. 58% was financed by the National Health Insurance Company and the rest by
      external donors (42%). Personnel salaries were the largest expense category
      (47%). The annual implementation costs of a good quality YFHSs in all 38 YFHCs of
      Moldova were estimated to be USD 1.0 million. The results of the threshold
      analysis indicate that the annual break-even impact points in a YFHC for: 1) STI
      services would be >364 averted STIs, 2) early pregnancy and contraceptive
      services >178 averted unwanted pregnancies, and 3) HIV services only >0.65
      averted new HIV infections. CONCLUSIONS: The costing results highlight the
      following: 1) significant additional resources would be required for
      implementation of a good quality national YFHS programme, 2) the four well
      performing YFHCs rely heavily on external funding (42%), 3) which raises
      questions about financial sustainability of the programme. At the same time
      results of the threshold analysis are encouraging. The result suggest that,
      together the three SRH components (STI, early pregnancy and contraception, and
      HIV) are potentially cost saving. High cost savings resulting from averted
      lifetime treatment cost of HIV infected persons are likely to off-set the costs
      of STIs and unwanted pregnancies.

PMID- 25047075
TI  - A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive
      Pseudomonas aeruginosa infection.
AB  - Sepsis and septic shock remain important medical problems with high mortality
      rates. Today's treatment is based mainly on using antibiotics to target the
      bacteria, without addressing the systemic inflammatory response, which is a major
      contributor to mortality in sepsis. Therefore, novel treatment options are
      urgently needed to counteract these complex sepsis pathologies. Heparin cofactor
      II (HCII) has recently been shown to be protective against Gram-negative
      infections. The antimicrobial effects were mapped to helices A and D of the
      molecule. Here we show that KYE28, a 28 amino acid long peptide representing
      helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia
      coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and
      Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28
      binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by
      decreasing NF-kappaB/AP-1 activation in vitro. In mouse models of LPS-induced
      shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory
      cytokine response. Finally, in an invasive Pseudomonas infection model, the
      peptide inhibited bacterial growth and reduced the pro-inflammatory response,
      which lead to a significant reduction of mortality. In summary, the peptide
      KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory
      responses represents a novel therapeutic candidate for invasive infections. 

PMID- 25047076
TI  - Differential Bees Flux Balance Analysis with OptKnock for in silico microbial
      strains optimization.
AB  - Microbial strains optimization for the overproduction of desired phenotype has
      been a popular topic in recent years. The strains can be optimized through
      several techniques in the field of genetic engineering. Gene knockout is a
      genetic engineering technique that can engineer the metabolism of microbial cells
      with the objective to obtain desirable phenotypes. However, the complexities of
      the metabolic networks have made the process to identify the effects of genetic
      modification on the desirable phenotypes challenging. Furthermore, a vast number
      of reactions in cellular metabolism often lead to the combinatorial problem in
      obtaining optimal gene deletion strategy. Basically, the size of a genome-scale
      metabolic model is usually large. As the size of the problem increases, the
      computation time increases exponentially. In this paper, we propose Differential
      Bees Flux Balance Analysis (DBFBA) with OptKnock to identify optimal gene
      knockout strategies for maximizing the production yield of desired phenotypes
      while sustaining the growth rate. This proposed method functions by improving the
      performance of a hybrid of Bees Algorithm and Flux Balance Analysis (BAFBA) by
      hybridizing Differential Evolution (DE) algorithm into neighborhood searching
      strategy of BAFBA. In addition, DBFBA is integrated with OptKnock to validate the
      results for improving the reliability the work. Through several experiments
      conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as
      the model organisms, DBFBA has shown a better performance in terms of
      computational time, stability, growth rate, and production yield of desired
      phenotypes compared to the methods used in previous works. 

PMID- 25047077
TI  - The submarine volcano eruption off El Hierro Island: effects on the scattering
      migrant biota and the evolution of the pelagic communities.
AB  - The submarine volcano eruption off El Hierro Island (Canary Islands) on 10
      October 2011 promoted dramatic perturbation of the water column leading to
      changes in the distribution of pelagic fauna. To study the response of the
      scattering biota, we combined acoustic data with hydrographic profiles and
      concurrent sea surface turbidity indexes from satellite imagery. We also
      monitored changes in the plankton and nekton communities through the eruptive and
      post-eruptive phases. Decrease of oxygen, acidification, rising temperature and
      deposition of chemicals in shallow waters resulted in a reduction of epipelagic
      stocks and a disruption of diel vertical migration (nocturnal ascent) of
      mesopelagic organisms. Furthermore, decreased light levels at depth caused by
      extinction in the volcanic plume resulted in a significant shallowing of the deep
      acoustic scattering layer. Once the eruption ceased, the distribution and
      abundances of the pelagic biota returned to baseline levels. There was no
      evidence of a volcano-induced bloom in the plankton community. 

PMID- 25047078
TI  - Modeling the impact of climate and landscape on the efficacy of white tailed deer
      vaccination for cattle tick control in northeastern Mexico.
AB  - Cattle ticks are distributed worldwide and affect animal health and livestock
      production. White tailed deer (WTD) sustain and spread cattle tick populations.
      The aim of this study was to model the efficacy of anti-tick vaccination of WTD
      to control tick infestations in the absence of cattle vaccination in a territory
      where both host species coexist and sustain cattle tick populations. Agent-based
      models that included land cover/landscape properties (patch size, distances to
      patches) and climatic conditions were built in a GIS environment to simulate WTD
      vaccine effectiveness under conditions where unvaccinated cattle shared the
      landscape. Published and validated information on tick life cycle was used to
      build models describing tick mortality and developmental rates. Data from
      simulations were applied to a large territory in northeastern Mexico where cattle
      ticks are endemic and WTD and cattle share substantial portions of the habitat.
      WTD movements were simulated together with tick population dynamics considering
      the actual landscape and climatic features. The size of the vegetation patches
      and the distance between patches were critical for the successful control of tick
      infestations after WTD vaccination. The presence of well-connected, large
      vegetation patches proved essential for tick control, since the tick could
      persist in areas of highly fragmented habitat. The continued application of one
      yearly vaccination on days 1-70 for three years reduced tick
      abundance/animal/patch by a factor of 40 and 60 for R. annulatus and R.
      microplus, respectively when compared to non-vaccinated controls. The study
      showed that vaccination of WTD alone during three consecutive years could result
      in the reduction of cattle tick populations in northeastern Mexico. Furthermore,
      the results of the simulations suggested the possibility of using vaccines to
      prevent the spread and thus the re-introduction of cattle ticks into tick-free
      areas. 

PMID- 25047080
TI  - The evolutionary consequences of disrupted male mating signals: an agent-based
      modelling exploration of endocrine disrupting chemicals in the guppy.
AB  - Females may select a mate based on signalling traits that are believed to
      accurately correlate with heritable aspects of male quality. Anthropogenic
      actions, in particular chemicals released into the environment, are now
      disrupting the accuracy of mating signals to convey information about male
      quality. The long-term prediction for disrupted mating signals is most commonly
      loss of female preference. Yet, this prediction has rarely been tested using
      quantitative models. We use agent-based models to explore the effects of rapid
      disruption of mating signals. In our model, a gene determines survival. Males
      signal their level of genetic quality via a signal trait, which females use to
      select a mate. We allowed this system of sexual selection to become established,
      before introducing a disruption between the male signal trait and quality, which
      was similar in nature to that induced by exogenous chemicals. Finally, we
      assessed the capacity of the system to recover from this disruption. We found
      that within a relatively short time frame, disruption of mating signals led to a
      lasting loss of female preference. Decreases in mean viability at the population
      level were also observed, because sexual-selection acting against newly arising
      deleterious mutations was relaxed. The ability of the population to recover from
      disrupted mating signals was strongly influenced by the mechanisms that promoted
      or maintained genetic diversity in traits under sexual selection. Our simple
      model demonstrates that environmental perturbations to the accuracy of male
      mating signals can result in a long-term loss of female preference for those
      signals within a few generations. What is more, the loss of this preference can
      have knock-on consequences for mean population fitness. 

PMID- 25047081
TI  - Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs
      anticoagulation alone to treat lower-extremity proximal deep vein thrombosis.
AB  - IMPORTANCE: The role of catheter-directed thrombolysis (CDT) in the treatment of
      acute proximal deep vein thrombosis (DVT) is controversial, and the nationwide
      safety outcomes are unknown. OBJECTIVES: The primary objective was to compare in
      hospital outcomes of CDT plus anticoagulation with those of anticoagulation
      alone. The secondary objective was to evaluate the temporal trends in the
      utilization and outcomes of CDT in the treatment of proximal DVT. DESIGN,
      SETTING, AND PARTICIPANTS: Observational study of patients with a principal
      discharge diagnosis of proximal or caval DVT from 2005 to 2010 in the Nationwide
      Inpatient Sample (NIS) database. We compared patients treated with CDT plus
      anticoagulation with the patients treated with anticoagulation alone. We used
      propensity scores to construct 2 matched groups of 3594 patients in each group
      for comparative outcomes analysis. MAIN OUTCOMES AND MEASURES: The primary study
      outcome was in-hospital mortality. The secondary outcomes included bleeding
      complications, length of stay, and hospital charges. RESULTS: Among a total of
      90,618 patients hospitalized for DVT (national estimate of 449,200
      hospitalizations), 3649 (4.1%) underwent CDT. The CDT utilization rates increased
      from 2.3% in 2005 to 5.9% in 2010. Based on the propensity-matched comparison,
      the in-hospital mortality was not significantly different between the CDT and the
      anticoagulation groups (1.2% vs 0.9%) (OR, 1.40 [95% CI, 0.88-2.25]) (P = .15).
      The rates of blood transfusion (11.1% vs 6.5%) (OR, 1.85 [95% CI, 1.57-2.20]) (P
      < .001), pulmonary embolism (17.9% vs 11.4%) (OR, 1.69 [95% CI, 1.49-1.94]) (P <
      .001), intracranial hemorrhage (0.9% vs 0.3%) (OR, 2.72 [95% CI, 1.40-5.30]) (P =
      .03), and vena cava filter placement (34.8% vs 15.6%) (OR, 2.89 [95% CI, 2.58
      3.23]) (P < .001) were significantly higher in the CDT group. The CDT group had
      longer mean (SD) length of stay (7.2 [5.8] vs 5.0 [4.7] days) (OR, 2.27 [95% CI,
      1.49-1.94]) (P < .001) and higher hospital charges ($85,094 [$69,121] vs $28,164
      [$42,067]) (P < .001) compared with the anticoagulation group. CONCLUSIONS AND
      RELEVANCE: In this study, we did not find any difference in the mortality between
      the CDT and the anticoagulation groups, but evidence of higher adverse events was
      noted in the CDT group. In the context of this observational data and continued
      improvements in technology, a randomized trial with outcomes such as mortality
      and postthrombotic syndrome is needed to definitively address this comparative
      effectiveness.

PMID- 25047082
TI  - An innovative model of culturally tailored health promotion groups for Cambodian
      survivors of torture.
AB  - Cambodians living in the U.S.A. suffer from depression, posttraumatic stress
      disorder (PTSD), and chronic medical disease at rates far in excess of national
      averages. The Harvard Program in Refugee Trauma's Cambodian Health Promotion
      Program seeks to address this burden of disease by offering them culturally
      tailored health education in a group setting. A health professional and a
      bicultural health educator co-facilitated a five-session health promotion group
      for Cambodian survivors of torture from 2007 to 2011. The program covered five
      major topics from Western and Cambodian worldviews. They included the meaning of
      health promotion, nutrition, exercise, stress management and sleep hygiene, and
      health practitioner-patient communication. The bicultural worker administered Pre
      and Post semi-structured Health Promotion Questionnaires. The data presented here
      are the results from 126 participants. Changes between the Pre and Post health
      promotion groups demonstrated significant improvements in health status,
      lifestyle activities, sleep, and depression. Participants revealed greater
      confidence in communicating with their primary health care practitioner.
      Culturally tailored Cambodian health promotion education administered in a small
      group setting may improve health and mental health behaviors. Culturally tailored
      health promotion education in a small group setting may promote healing in
      survivors of torture. It is an intervention worthy of further research and
      development. 

PMID- 25047084
TI  - The effect of ice skating on psychological well-being and sleep quality of
      children with visual or hearing impairment.
AB  - PURPOSE: Physical exercise and sports have a key role in preventing physical and
      psychiatric problems in children. However, children with a disability often
      experience difficulty participating in physical activity due to a lack of
      suitable opportunities. Participation in an accessible sport is particularly
      important for these children, but studies examining which sports are beneficial
      for which disability groups are rare. In this study, we assessed the effects of
      ice skating on the psychological well-being, self-concept, and sleep quality of
      children with hearing or visual impairment. METHOD: Forty students (20 visually
      impaired and 20 hearing impaired) aged 8-16 were included in a regular ice
      skating programme for three months. We examined the sleep quality, self-concept,
      and behavioural and emotional states of the children before and after
      participating in the programme. RESULTS: There was a significant improvement in
      self-concept, behavioural and emotional problems, and sleep quality (p < 0.05 for
      each) of the children with hearing impairment. Although the sleep quality (p =
      0.019) and emotional problem scores (p = 0.000) of the visually impaired children
      improved; self-concept, peer relations and hyperactivity scores of these children
      worsened (p < 0.05 for each). CONCLUSION: Ice skating is one of the popular sport
      alternatives that gives children the opportunity to exercise and have fun
      together. The results of this study revealed that regular ice skating programmes
      may have positive effects on the psychological well-being of children with
      hearing impairment. Despite some positive effects, caution must be use when
      including visually impaired children in ice skating programmes. Generalization of
      the study's outcomes is limited as the study group were residential students
      enrolled in special education institutions for children who are blind or deaf.
      IMPLICATIONS FOR REHABILITATION: Ice skating is a community-based sport and a
      popular leisure activity that can also have benefits for people with
      disabilities. Ice skating and children with hearing impairment: Self-concept,
      behavioural and emotional problems, and sleep quality of the children with
      hearing impairment significantly improved after ice skating. Ice skating
      programmes may be considered as a rehabilitation alternative for children with
      hearing impairment. Ice skating and children with visual impairment: Caution must
      be use when including children with visual impairment in ice skating programmes
      because of possible negative psychological outcomes. Balance exercises before
      starting the practices on ice should be considered for preventing some possible
      negative outcomes in children with visual impairment.

PMID- 25047083
TI  - Microstructural changes in the striatum and their impact on motor and
      neuropsychological performance in patients with multiple sclerosis.
AB  - Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis
      (MS) that has been previously assessed with diffusion tensor imaging (DTI).
      Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased
      in MS patients, and correlates with disability scores. Despite the established
      role of the striatum and thalamus in motor control, mood and cognition, the
      impact of DTI changes within these structures on motor and neuropsychological
      performance has not yet been specifically addressed in MS. We investigated DTI
      metrics of deep GM nuclei and their potential association with mobility and
      neuropsychological function. DTI metrics from 3T MRI were assessed in the
      caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the
      patients underwent neuropsychological testing. FA of the caudate and putamen was
      higher in MS patients compared to controls. Caudate FA correlated with Expanded
      Disability Status Scale score, Ambulation Index, and severity of depressive
      symptomatology. Putamen and thalamus FA correlated with deficits in memory tests.
      In contrast, cerebral white matter (WM) lesion burden showed no significant
      correlation with any of the disability, mobility and psychometric parameters. Our
      findings support evidence of FA changes in the basal ganglia in MS patients, as
      well as deep GM involvement in disabling features of MS, including mobility and
      cognitive impairment. Deep GM FA appears to be a more sensitive correlate of
      disability than WM lesion burden. 

PMID- 25047085
TI  - Modular structure facilitates mosaic evolution of the brain in chimpanzees and
      humans.
AB  - Different brain components can evolve in a coordinated manner or they can show
      divergent evolutionary trajectories according to a mosaic pattern of variation.
      Understanding the relationship between these brain evolutionary patterns, which
      are not mutually exclusive, can be informed by the examination of intraspecific
      variation. Our study evaluates patterns of brain anatomical covariation in
      chimpanzees and humans to infer their influence on brain evolution in the hominin
      clade. We show that chimpanzee and human brains have a modular structure that may
      have facilitated mosaic evolution from their last common ancestor. Spatially
      adjacent regions covary with one another to the strongest degree and separated
      regions are more independent from each other, which might be related to a
      predominance of local association connectivity. Despite the undoubted importance
      of developmental and functional factors in determining brain morphology, we find
      that these constraints are subordinate to the primary effect of local spatial
      interactions. 

PMID- 25047086
TI  - The impact of hot charge carrier mobility on photocurrent losses in polymer-based
      solar cells.
AB  - A typical signature of charge extraction in disordered organic systems is
      dispersive transport, which implies a distribution of charge carrier mobilities
      that negatively impact on device performance. Dispersive transport has been
      commonly understood to originate from a time-dependent mobility of hot charge
      carriers that reduces as excess energy is lost during relaxation in the density
      of states. In contrast, we show via photon energy, electric field and film
      thickness independence of carrier mobilities that the dispersive photocurrent in
      organic solar cells originates not from the loss of excess energy during hot
      carrier thermalization, but rather from the loss of carrier density to trap
      states during transport. Our results emphasize that further efforts should be
      directed to minimizing the density of trap states, rather than controlling
      energetic relaxation of hot carriers within the density of states. 

PMID- 25047088
TI  - Photophysical properties of cis-Mo2 quadruply bonded complexes and observation of
      photoinduced electron transfer to titanium dioxide.
AB  - The compounds cis-Mo2(DAniF)2(L)2 have been prepared, where DAniF = (N,N')-p
      dianisyl formamidinate and L = thienyl-2-carboxylate (Th), 2,2'-bithienyl-5
      carboxylate (BTh), and 2,2':5',5"-terthienyl-5-carboxylate (TTh). The compounds
      have been characterized by proton nuclear magnetic resonance ((1)H NMR),
      ultraviolet-visible (UV-vis) absorption and emission, differential pulse
      voltammetry, and time-resolved transient absorption and infrared (IR)
      spectroscopy. An X-ray crystal structure was obtained for the thienyl complex.
      The related salt [(n)Bu4N]2[Mo2(DAniF)2(TTh-CO2)2], where TTh-CO2 = 2,2':5',2"
      terthienyl-5,5"-dicarboxylate, has also been prepared and employed in the
      attachment of the complex to TiO2 nanoparticles. The latter have been
      characterized by ground-state Fourier transform infrared spectroscopy (FTIR) and
      femtosecond time-resolved IR spectroscopy. The time-resolved data provide
      evidence for sub-picosecond charge injection from the Mo2 center to the
      semiconducting oxide particle. 

PMID- 25047087
TI  - MicroRNA profile in very young women with breast cancer.
AB  - BACKGROUND: Breast cancer is rarely diagnosed in very young women (35 years old
      or younger), and it often presents with distinct clinical-pathological features
      related to a more aggressive phenotype and worse prognosis when diagnosed at this
      early age. A pending question is whether breast cancer in very young women arises
      from the deregulation of different underlying mechanisms, something that will
      make this disease an entity differentiated from breast cancer diagnosed in older
      patients. METHODS: We performed a comprehensive study of miRNA expression using
      miRNA Affymetrix2.0 array on paraffin-embedded tumour tissue of 42 breast cancer
      patients 35 years old or younger, 17 patients between 45 and 65 years old and 29
      older than 65 years. Data were statistically analyzed by t-test and a
      hierarchical clustering via average linkage method was conducted. Results were
      validated by qRT-PCR. Putative targeted pathways were obtained using DIANA
      miRPath online software. RESULTS: The results show a differential and unique
      miRNA expression profile of 121 miRNAs (p-value <0.05), 96 of those with a FDR
      value <0.05. Hierarchical clustering grouped the samples according to their age,
      but not by subtype nor by tumour characteristics. We were able to validate by qRT
      PCR differences in the expression of 6 miRNAs: miR-1228*, miR-3196, miR-1275, miR
      92b, miR-139 and miR-1207. Moreover, all of the miRNAs maintained the expression
      trend. The validated miRNAs pointed out pathways related to cell motility,
      invasion and proliferation. CONCLUSIONS: The study suggests that breast cancer in
      very young women appears as a distinct molecular signature. To our knowledge,
      this is the first time that a validated microRNA profile, distinctive to breast
      cancer in very young women, has been presented. The miRNA signature may be
      relevant to open an important field of research in order to elucidate the
      underlying mechanism in this particular disease, which in a more clinical
      setting, could potentially help to identify therapeutic targets in this
      particular set of patients.

PMID- 25047089
TI  - Evaluation of the effect of cardiac rehabilitation on left atrial and left
      ventricular function and its relationship with changes in arterial stiffness in
      patients with acute myocardial infarction.
AB  - BACKGROUND: The main aim of this study was to detect the possible early effect of
      cardiac rehabilitation (CR) on left atrium (LA) and left ventricle (LV) function
      and relation to aortic stiffness in patients with acute myocardial infarction
      (AMI). METHODS: Fifty-four patients with AMI were enrolled in this study. Left
      atrial strain analysis was performed by two-dimensional speckle tracking
      echocardiography. The deceleration time (DT) was measured by pulsed-wave Doppler.
      The ratio of E/e' to LA peak strain was used to estimate the LA stiffness
      (Stiffnessstrain ) Aortic elasticity parameters were calculated using the
      formulas including aortic systolic and diastolic diameter with M-Mode
      echocardiography and blood pressure. Anterior wall aortic expansion velocity was
      measured by tissue Doppler imaging. RESULTS: Left ventricle ejection fraction
      (EF) and LA functional parameters were significantly better in trained subjects.
      Also in training group, the LV diastolic functional parameters were better in CR
      group than the control group. Aortic elasticity parameters were better with CR.
      CONCLUSIONS: In patients with CR, an increase in LA strain was correlated with
      increase in aortic strain and improved aortic distensibility, likely indicating
      favorable LA and aortic interactions with exercise training.

PMID- 25047090
TI  - A randomized, placebo-controlled trial to determine the course of
      aminotransferase elevation during prolonged acetaminophen administration.
AB  - BACKGROUND: Acetaminophen administration for more than 4 days causes
      aminotransferase elevation in some subjects. The objective of this randomized,
      placebo-controlled trial is to describe the course of alanine aminotransferase
      (ALT) elevation in subjects administered 4 g/day of acetaminophen for at least 16
      days. METHODS: A randomized, placebo controlled trial of acetaminophen (4 g/day)
      vs placebo. Subjects were healthy volunteers with normal liver enzymes. The
      primary outcome was the course of ALT during acetaminophen administration. All
      subjects were treated for a minimum of 16 days. Subjects with ALT elevation at
      day 16 were continued on treatment until these elevations resolved up to a
      maximum of 40 days. Subjects were also evaluated for elevation of INR or serum
      bilirubin as evidence of hepatic dysfunction. RESULTS: 157/205 (77%) completed
      acetaminophen subjects had no ALT elevation or transient elevations that resolved
      by day 16. Of the 48 subjects who had ALT elevations at study day 16, 47
      continued on acetaminophen and had resolution by study day 40. One acetaminophen
      subject did not have resolution by study day 40, and the course of
      aminotransferase elevation suggests an alternative cause. One placebo subject had
      an ALT elevation at day 16 that resolved by day 22. The highest observed ALT
      among all acetaminophen subjects was 191 IU/L. The mean ALT at day 16 was 4.4
      IU/L higher for the acetaminophen than for the placebo group. No subject
      developed liver dysfunction. CONCLUSIONS: A minority of subjects treated with 4
      g/day of acetaminophen for 16 days will have low-grade aminotransferase
      elevations that are not accompanied by liver dysfunction and resolve if
      administration is continued. TRIALS REGISTRATION: Clintrials.gov NCT00743093
      registered August 26, 2008.

PMID- 25047091
TI  - The 'Timing of Androgen-Deprivation therapy in incurable prostate cancer'
      protocol (TOAD)--where are we now? Synopsis of the Victorian Cooperative Oncology
      Group PR 01-03 and Trans-Tasman Radiation Oncology Group 03.06 clinical trial.
AB  - OBJECTIVE: To outline the development of the 'Timing of Androgen Deprivation'
      (TOAD) protocol, a collaborative randomised clinical trial under the auspices of
      the Cancer Council Victoria, the Trans-Tasman Radiation Oncology Group, and the
      Urological Society of Australia and New Zealand (USANZ), which opened to
      recruitment in 2004. PATIENTS AND METHODS: The principal hypothesis for the trial
      was that the early introduction of androgen-deprivation therapy (ADT;
      experimental arm) at the time when curative therapies are no longer considered an
      option, would improve overall survival for these patients, whilst maintaining an
      acceptable quality of life; compared with waiting for disease progression or the
      development of symptoms (control arm). An increase in overall survival at 5 years
      of 10% was judged to be clinically worthwhile. RESULTS: Recruitment was slow,
      with fewer than half of the protocol requirement of 750 patients eventually
      accrued, but nonetheless it is considered that the trial will still contribute a
      major source of evidence in this area. The study closed to follow-up at the end
      of 2013, with data analysis commencing mid-2014, and with the primary publication
      anticipated to be submitted by the end of 2014. CONCLUSION: The question of
      timing of ADT remains relevant in the current era of newer and more varied
      treatment methods. Even with the advent of novel chemotherapy and the biological
      agents that are undergoing investigation for progressively earlier disease
      stages, the dilemma of when to commence palliative treatment in an asymptomatic
      patient will remain, unless or until these agents are shown to increase overall
      survival. The TOAD trial will contribute to answering at least in part, some of
      these questions.

PMID- 25047092
TI  - Endoplasmic reticulum stress: key promoter of rosacea pathogenesis.
AB  - Recent scientific interest in the pathogenesis of rosacea focuses on abnormally
      high facial skin levels of cathelicidin and the trypsin-like serine protease
      kallikrein 5 (KLK5) that cleaves the cathelicidin precursor protein into the
      bioactive fragment LL-37, which exerts crucial proinflammatory, angiogenic and
      antimicrobial activities. Furthermore, increased expression of toll-like receptor
      2 (TLR2) has been identified in rosacea skin supporting the participation of the
      innate immune system. Notably, TLRs are expressed on sensory neurons and increase
      neuronal excitability linking TLR signalling to the transmission of
      neuroinflammatory responses. It is the intention of this viewpoint to present a
      unifying concept that links all known clinical trigger factors of rosacea such as
      UV irradiation, heat, skin irritants and special foods to one converging point:
      enhanced endoplasmic reticulum (ER) stress that activates the unfolded protein
      response (UPR). ER stress via upregulation of transcription factor ATF4 increases
      TLR2 expression, resulting in enhanced production of cathelicidin and KLK5
      mediating downstream proinflammatory, angiogenic and antimicrobial signalling.
      The presented concept identifies rosacea trigger factors as environmental
      stressors that enhance the skin's ER stress response. Exaggerated cutaneous ER
      stress that stimulates the TLR2-driven inflammatory response may involve
      sebocytes, keratinocytes, monocyte-macrophages and sensory cutaneous neurons.
      Finally, all antirosacea drugs are proposed to attenuate the ER stress signalling
      cascade at some point. Overstimulated ER stress signalling may have
      evolutionarily evolved as a compensatory mechanism to balance impaired vitamin D
      driven LL-37-mediated antimicrobial defenses due to lower exposure of UV-B
      irradiation of the northern Celtic population. 

PMID- 25047093
TI  - Effects of sulfhydryl compounds, carbohydrates, organic acids, and sodium sulfite
      on the formation of lysinoalanine in preserved egg.
AB  - To identify inhibitors for lysinoalanine formation in preserved egg, sulfhydryl
      compounds (glutathione, L-cysteine), carbohydrates (sucrose, D-glucose, maltose),
      organic acids (L-ascorbic acid, citric acid, DL-malic acid, lactic acid), and
      sodium sulfite were individually added at different concentrations to a pickling
      solution to prepare preserved eggs. Lysinoalanine formation as an index of these
      10 substances was determined. Results indicate that glutathione, D-glucose,
      maltose, L-ascorbic acid, citric acid, lactic acid, and sodium sulfite all
      effectively diminished lysinoalanine formation in preserved egg albumen and yolk.
      When 40 and 80 mmol/L of sodium sulfite, citric acid, L-ascorbic acid, and D
      glucose were individually added into the pickling solution, the inhibition rates
      of lysinoalanine in the produced preserved egg albumen and yolk were higher.
      However, the attempt of minimizing lysinoalanine formation was combined with the
      premise of ensuring preserved eggs quality. Moreover, the addition of 40 and 80
      mmol/L of sodium sulfite, 40 and 80 mmol/L of D-glucose, 40 mmol/L of citric
      acid, and 40 mmol/L of L-ascorbic acid was optimal to produce preserved eggs. The
      corresponding inhibition rates of lysinoalanine in the albumen were approximately
      76.3% to 76.5%, 67.6% to 67.8%, 74.6%, and 74.6%, and the corresponding
      inhibition rates of lysinoalanine in the yolk were about 68.7% to 69.7%, 50.6% to
      51.8%, 70.4%, and 57.8%. It was concluded that sodium sulfite, D-glucose, L
      ascorbic, and citric acid at suitable concentrations can be used to control the
      formation of lysinoalanine during preserved egg processing.

PMID- 25047094
TI  - Dental fear and expected effectiveness of destructive coping as predictors of
      children's uncooperative intentions in dental settings.
AB  - AIM: To explore the mechanisms by which some children select disruptive
      behaviours to cope with stressful dental events. In particular, the relationships
      between dental fear, expected effectiveness of destructive coping, and intentions
      of displaying uncooperative behaviours were analysed. DESIGN: Participants were
      170 children who filled out a questionnaire survey. Descriptive statistics by
      gender and group age as well as comparisons of means were calculated. Spearman's
      rho correlation coefficients and binary logistic regression analysis were used to
      test hypotheses of the relationships among variables. RESULTS: Both dental fear
      and the expected effectiveness of destructive coping strategies were
      significantly associated with children's uncooperative intentions at the dentist.
      In addition, children who strongly endorsed the effectiveness of destructive
      coping strategies had a higher probability of uncooperative intentions as dental
      fear increased. In contrast, this relationship was not statistically significant
      among children who did not expect negative behaviours to be effective.
      CONCLUSIONS: Children's expectations about the effectiveness of destructive
      coping behaviours can help explain variations in the use of these strategies in
      stressful dental situations. Dental fear as well as children's inadequate
      expectancies about coping alternatives should be explored and targeted to prevent
      and modify uncooperative behaviour intentions at the dentist.

PMID- 25047095
TI  - Novel mutation 928G>C of MEN1 gene in a familial multiple endocrine neoplasia
      type 1 case (MEN1) with co-existence of insulinoma and glucagonoma.

PMID- 25047096
TI  - Toward Understanding the Child's Experience in the Process of Parentification:
      Young Adults' Reflections on Growing up With a Depressed Parent.
AB  - This article reports on a qualitative study with 21 young adults who grew up with
      a depressed parent. We examined how young adults make sense of their childhood
      experiences of parental depression and how their retrospective reflections help
      us to understand the experiences of children and the processes of
      parentification. Participants recounted that their childhood consisted mainly of
      actions in the service of family well-being. At that time, they reflected on
      their own experiences only rarely. In adolescence, there was an evolution toward
      a greater consideration for oneself and a repositioning within the family. In the
      discussion, we explore the therapeutic implications of this study--and in
      particular--the meaningfulness of silence in the family process of
      parentification.

PMID- 25047097
TI  - Carrier screening of RTEL1 mutations in the Ashkenazi Jewish population.
AB  - Hoyeraal-Hreidarsson syndrome (HH) is a clinically severe variant of dyskeratosis
      congenita (DC), characterized by cerebellar hypoplasia, microcephaly,
      intrauterine growth retardation, and severe immunodeficiency in addition to
      features of DC. Germline mutations in the RTEL1 gene have recently been
      identified as causative of HH. In this study, the carrier frequency for five
      RTEL1 mutations that occurred in individuals of Ashkenazi Jewish descent was
      investigated in order to advise on including them in existing clinical mutation
      panels for this population. Our screening showed that the carrier frequency for
      c.3791G>A (p.R1264H) was higher than expected, 1% in the Ashkenazi Orthodox and
      0.45% in the general Ashkenazi Jewish population. Haplotype analyses suggested
      the presence of a common founder. We recommend that the c.3791G>A RTEL1 mutation
      be considered for inclusion in carrier screening panels in the Ashkenazi
      population. 

PMID- 25047098
TI  - The expression and significance of five types of miRNAs in breast cancer.
AB  - BACKGROUND: This study aimed to investigate the expression and significance of 5
      types of miRNAs in breast cancer to provide a theoretical and practical
      foundation for using these miRNAs in the diagnosis and treatment of breast
      cancer, thereby improving medical services. MATERIAL/METHODS: Stem-loop real-time
      RT-PCR was used to detect the expression levels of miR-145, miR-21, miR-10b, miR
      125a, and miR-206 in 35 cases of breast cancer and adjacent normal breast
      tissues, and to analyze the relationship of miRNAs expression with
      clinicopathological features of breast cancer. The expression levels of estrogen
      receptor (ER) and progesterone receptor (PR) were examined by
      immunohistochemistry. Fluorescence in situ hybridization was used for the
      detection of HER-2 and TOP 2A. RESULTS: The expression levels of miR-145, miR
      125a, and miR-206 in breast cancer were lower than those in adjacent normal
      tissues. MiR-145 was negatively correlated with tumor size, lymph node
      metastasis, ER, HER-2, and TOP 2A (P<0.05), regardless of age, menstruation, and
      PR. MiR-125a was correlated with negative node status, negative HER-2 status
      (P<0.05), whereas tumor size, age, menstruation, ER, and PR were independent
      factors. MiR-206 expression was correlated with negative ER status, negative PR
      status, and negative HER-2 status (P<0.05), regardless of age, menstruation,
      lymph node metastasis, and TOP 2A. MiR-21 and miR-10b expression in breast cancer
      tissues was significantly higher than that in adjacent tissues (P<0.05). MiR-21
      in post-menstrual patients with lymph node metastasis was highly expressed
      (P<0.05), and had no correlations with tumor size, ER, PR, and TOP 2A expression.
      MiR-10b expression was positively correlated with breast cancer tumor size, lymph
      node metastasis, and TOP 2A status (P<0.05), but had no correlations with age,
      menstruation, ER, PR, and HER-2. CONCLUSIONS: MiR-145, miR-21, miR-10b, miR-125a,
      and miR-206 may play important roles in breast cancer development and invasion.

PMID- 25047099
TI  - Positive feedback loop between introductions of non-native marine species and
      cultivation of oysters in Europe.
AB  - With globalization, agriculture and aquaculture activities are increasingly
      affected by diseases that are spread through movement of crops and stock. Such
      movements are also associated with the introduction of non-native species via
      hitchhiking individual organisms. The oyster industry, one of the most important
      forms of marine aquaculture, embodies these issues. In Europe disease outbreaks
      affecting cultivated populations of the naturalized oyster Crassostrea gigas
      caused a major disruption of production in the late 1960s and early 1970s.
      Mitigation procedures involved massive imports of stock from the species' native
      range in the northwestern Pacific from 1971 to 1977. We assessed the role stock
      imports played in the introduction of non-native marine species (including
      pathogens) from the northwestern Pacific to Europe through a methodological and
      critical appraisal of record data. The discovery rate of non-native species (a
      proxy for the introduction rate) from 1966 to 2012 suggests a continuous vector
      activity over the entire period. Disease outbreaks that have been affecting
      oyster production since 2008 may be a result of imports from the northwestern
      Pacific, and such imports are again being considered as an answer to the crisis.
      Although successful as a remedy in the short and medium terms, such
      translocations may bring new diseases that may trigger yet more imports (self
      reinforcing or positive feedback loop) and lead to the introduction of more
      hitchhikers. Although there is a legal framework to prevent or reduce these
      introductions, existing procedures should be improved.

PMID- 25047100
TI  - Exploring the phase space of time of flight mass selected Pt(x)Y nanoparticles.
AB  - Mass-selected nanoparticles can be conveniently produced using magnetron
      sputtering and aggregation techniques. However, numerous pitfalls can compromise
      the quality of the samples, e.g. double or triple mass production, dendritic
      structure formation or unpredicted particle composition. We stress the importance
      of transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS)
      and ion scattering spectroscopy (ISS) for verifying the morphology, size
      distribution and chemical composition of the nanoparticles. Furthermore, we
      correlate the morphology and the composition of the PtxY nanoparticles with their
      catalytic properties for the oxygen reduction reaction. Finally, we propose a
      completely general diagnostic method, which allows us to minimize the occurrence
      of undesired masses. 

PMID- 25047103
TI  - Extraction and Analysis of Risk Elements for Korean Homecare Patients with Senile
      Dementia.
AB  - The purpose of this study is to provide information for the protection of Korean
      homecare patients with senile dementia by investigating accident cases using a
      survey. With the survey of accident cases, the caregivers of 55 Korean homecare
      patients with senile dementia (75.9 +/- 7.0 years) were administered the short
      form of the Samsung Dementia Questionnaire (S-SDQ) and an activities of daily
      living (ADL) test. Twelve risk elements were extracted. The order of frequency of
      occurrence from highest to lowest was "egress," "fall," "violence," "collision,"
      "gas accident," "slip," "faucet misuse," "overeating," "drop," "discharge,"
      "weird eating," and "self-injury." The percentage of risk elements resulting in
      physical harm was 40.1% across all risk elements. The risk elements resulting in
      the most physical harm were "fall," "collision," "slip," and "drop,"
      respectively. Regarding the location of occurrence of risk elements, risk
      elements resulting in physical harm showed no significant differences between
      indoors and outdoors. Some risk elements, such as "egress," "fall," and "gas
      accident" happened concurrently with more than four other elements, while
      "collision," "drop," and "violence" happened together with more than two other
      elements. "Slip" happened significantly more often in the low ADL score group,
      while "gas accident" happened significantly more often in the high ADL score
      group. This study provides basic information about monitoring factors to protect
      senior homecare patients with senile dementia. 

PMID- 25047101
TI  - MAPK and NF-kappaB pathways are involved in bisphenol A-induced TNF-alpha and IL
      6 production in BV2 microglial cells.
AB  - Microglial activation has been reported to play an important role in
      neurodegenerative diseases by producing pro-inflammatory cytokines. Bisphenol A
      (BPA, 2,2-bis (4-hydroxyphenyl) propane), known as a ubiquitous endocrine
      disrupting chemical, is reported to perform both mimic- and anti-estrogen
      properties; however, whether it affects cytokine production or immune response in
      central nervous system remains unclear. The present study was aimed to explore
      whether BPA was involved in inflammatory action and to investigate the potential
      mechanisms in microglial cells. BV2, the murine microglial cell line, was used in
      the present work as the cell model. BPA-associated morphologic changes, cytokine
      responses, and signaling events were examined using immunofluorescence analysis,
      real-time PCR, enzyme-linked immunosorbent assay, and western blot. Our results
      indicated that BPA increased BV2 cells activation and simultaneously elevated
      tumor necrosis factor-alpha and interleukin 6 expression, which could be
      partially reversed by estrogen receptor antagonist, ICI182780. In addition, the c
      Jun N-terminal protein kinase (JNK) inhibitor (SP600125), rather than ERK1/2
      blocker (PD98059), displayed anti-inflammatory properties on BPA-elicited
      cytokine responses. Moreover, the inflammatory transcription factor NF-kappaB was
      specifically activated by BPA as well. These results, taken together, suggested
      that BPA may have functional effects on the response of microglial cell
      activation via, in part, the estrogen receptor, JNK, ERK mitogen-activated
      protein kinase, and NF-kappaB signaling pathways with its subsequent influence on
      pro-inflammatory action. 

PMID- 25047104
TI  - Clinical course of juvenile myelomonocytic leukemia in the blast crisis phase
      treated by acute myeloid leukemia-oriented chemotherapy and allogeneic
      hematopoietic stem cell transplantation.
AB  - Juvenile myelomonocytic leukemia (JMML) is a mixed myeloproliferative and
      myelodysplastic disorder that occurs in early childhood. The clinical course of
      JMML is highly variable. A third of patients follow a relatively indolent course,
      although approximately 15% cases are thought to develop acute myeloid leukemia,
      referred to as blast crisis. The etiology and clinical characteristics of blast
      crisis remain unclear. We document the case of a 27-month-old boy who presented
      with hepatosplenomegaly, skin rash, and lymphadenopathy. An initial diagnosis of
      acute erythroid leukemia was made according to the French-American-British
      classification. Following estimation of hypersensitivity to GM-CSF and genetic
      analysis of PTPN11, he was diagnosed with JMML in the blast crisis phase.
      Although he had several poor prognostic factors, including monosomy 7 and high
      HbF percentage, he achieved partial remission after treatment with acute myeloid
      leukemia-oriented chemotherapy followed by allogeneic hematopoietic stem cell
      transplantation. He has been in complete remission for over 6 years.

PMID- 25047105
TI  - Distinct contributions of extrastriate body area and temporoparietal junction in
      perceiving one's own and others' body.
AB  - The right temporoparietal cortex plays a critical role in body representation.
      Here, we applied repetitive transcranial magnetic stimulation (rTMS) over right
      extrastriate body area (EBA) and temporoparietal junction (TPJ) to investigate
      their causative roles in perceptual representations of one's own and others'
      body. Healthy women adjusted size-distorted pictures of their own body or of the
      body of another person according to how they perceived the body (subjective task)
      or how others perceived it (intersubjective task). In keeping with previous
      reports, at baseline, we found an overall underestimation of body size.
      Crucially, EBA-rTMS increased the underestimation bias when participants adjusted
      the images according to how others perceived their own or the other woman's body,
      suggesting a specific role of EBA in allocentric body representations.
      Conversely, TPJ-rTMS increased the underestimation bias when participants
      adjusted the body of another person, either a familiar other or a close friend,
      in both subjective and intersubjective tasks, suggesting an involvement of TPJ in
      representing others' bodies. These effects were body-specific, since no TMS
      induced modulation was observed when participants judged a familiar object. The
      results suggest that right EBA and TPJ play active and complementary roles in the
      complex interaction between the perceptions of one's own and other people's body.

PMID- 25047106
TI  - Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl
      /HCO3- exchanger.
AB  - BACKGROUND: Cardiac hypertrophy is central to the etiology of heart failure.
      Understanding the molecular pathways promoting cardiac hypertrophy may identify
      new targets for therapeutic intervention. Sodium-proton exchanger (NHE1) activity
      and expression levels in the heart are elevated in many models of hypertrophy
      through protein kinase C (PKC)/MAPK/ERK/p90RSK pathway stimulation. Sustained
      NHE1 activity, however, requires an acid-loading pathway. Evidence suggests that
      the Cl-/HCO3- exchanger, AE3, provides this acid load. Here we explored the role
      of AE3 in the hypertrophic growth cascade of cardiomyocytes. METHODS: AE3
      deficient (ae3-/-) mice were compared to wildtype (WT) littermates to examine the
      role of AE3 protein in the development of cardiomyocyte hypertrophy. Mouse hearts
      were assessed by echocardiography. As well, responses of cultured cardiomyocytes
      to hypertrophic stimuli were measured. pH regulation capacity of ae3-/- and WT
      cardiomyocytes was assessed in cultured cells loaded with the pH-sensitive dye,
      BCECF-AM. RESULTS: ae3-/- mice were indistinguishable from wild type (WT) mice in
      terms of cardiovascular performance. Stimulation of ae3-/- cardiomyocytes with
      hypertrophic agonists did not increase cardiac growth or reactivate the fetal
      gene program. ae3-/- mice are thus protected from pro-hypertrophic stimulation.
      Steady state intracellular pH (pHi) in ae3-/- cardiomyocytes was not
      significantly different from WT, but the rate of recovery of pHi from imposed
      alkalosis was significantly slower in ae3-/- cardiomyocytes. CONCLUSIONS: These
      data reveal the importance of AE3-mediated Cl-/HCO3- exchange in cardiovascular
      pH regulation and the development of cardiomyocyte hypertrophy. Pharmacological
      antagonism of AE3 is an attractive approach in the treatment of cardiac
      hypertrophy.

PMID- 25047111
TI  - Roles of cathelicidins in inflammation and bone loss.
AB  - Body surface tissues, such as the oral cavity, contact directly with the external
      environment and are continuously exposed to microbial insults. Cathelicidins are
      a family of antimicrobial peptides that are found in mammalian species. Humans
      and mice have only one cathelicidin. Cathelicidins are expressed in a variety of
      surface tissues. In addition, they are abundantly expressed in bone and bone
      marrow. Infectious stimuli upregulate the expression of cathelicidins, which play
      sentinel roles in allowing the tissues to fight against microbial challenges.
      Cathelicidins disrupt membranes of microorganisms and kill them. They also
      neutralize microbe-derived pathogens, such as lipopolysaccharide (LPS) and
      flagellin. Besides their antimicrobial functions, cathelicidins can also control
      actions of host cells, such as chemotaxis, proliferation, and cytokine
      production, through binding to the receptors expressed on them. LPS and flagellin
      induce osteoclastogenesis and the production of cathelicidins, which can in turn
      inhibit osteoclastogenesis. Thus, cathelicidins contribute to maintaining
      microbiota-host homeostasis and promoting repair responses to inflammatory
      insults. In this review, we describe recent findings on the multiple roles of
      cathelicidins in host defense. We also discuss the significance of the human
      cathelicidin, LL-37, as a pharmaceutical target for the treatment of inflammation
      and bone loss in infectious diseases, such as periodontitis. 

PMID- 25047112
TI  - Study of beta-catenin, E-cadherin and vimentin in oral squamous cell carcinoma
      with and without lymph node metastases.
AB  - BACKGROUND: Despite great improvement in the surgical treatment and adjunctive
      therapy for oral squamous cell carcinoma (OSCC), prognosis remains dismal in
      advanced cases. Regional metastatic disease is known to reduce recurrence free
      survival and disease specific survival significantly. The present study was
      conducted to evaluate the role of cell adhesion molecules beta-catenin, E
      cadherin and vimentin in predicting tumour metastasis of OSCC. METHODS: A total
      of sixty cases of oral squamous cell carcinoma were included for the study which
      comprised of 30 cases with lymph node metastases and 30 cases without metastases.
      Immunohistochemistry was performed for beta-catenin, E-cadherin and vimentin on
      both the test groups along with 30 controls from normal buccal mucosa and
      inflammatory lesions each. RESULTS: There was no significant difference between
      the immunoreactivity for beta-catenin, E-cadherin and vimentin between OSCC with
      and without lymph node metastases. Vimentin immunopositivity was noted with
      varying intensity in all cases of OSCC. CONCLUSIONS: E-cadherin and beta-catenin
      are probably not the key determinants for regional metastases in OSCC. The role
      of vimentin expression in OSCC and metastases is controversial and needs to be
      studied further. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/6506095201182002.

PMID- 25047114
TI  - New mono- and diethynylsiloxysilsesquioxanes--efficient procedures for their
      synthesis.
AB  - Ethynyl-substituted siloxysilsesquioxanes are promising building blocks for a
      wide range of substances based on a POSS/DDSQ core, especially for (oligo
      )polymer syntheses and modifications (the formation of hybrid materials with
      interesting photophysical and mechanical properties). In this study, we report on
      a series of new mono- and diethynylsiloxysilsesquioxanes formed via an efficient
      and highly selective one-pot process from silsesquioxanes with reactive Si-OH
      groups based on sequential condensation, hydrolysis, chlorination and
      substitution reactions. All newly synthesized compounds were isolated and
      characterized by spectroscopic methods. 

PMID- 25047113
TI  - Chitinase 3-like 1 is induced by Plasmodium falciparum malaria and predicts
      outcome of cerebral malaria and severe malarial anaemia in a case-control study
      of African children.
AB  - BACKGROUND: Severe and fatal malaria are associated with dysregulated host
      inflammatory responses to infection. Chitinase 3-like 1 (CHI3L1) is a secreted
      glycoprotein implicated in regulating immune responses. Expression and function
      of CHI3L1 in malaria infection were investigated. METHODS: Plasma levels of
      CHI3L1 were quantified in a case-control study of Ugandan children presenting
      with Plasmodium falciparum malaria. CHI3L1 levels were compared in children with
      uncomplicated malaria (UM; n = 53), severe malarial anaemia (SMA; n = 59) and
      cerebral malaria (CM; n = 44) using the Kruskall Wallis-test, and evaluated for
      utility in predicting fatal (n = 23) versus non-fatal (n = 80) outcomes in severe
      disease using the Mann Whitney U test, receiver operating characteristic curves,
      and combinatorial analysis. Co-culture of P. falciparum with human peripheral
      blood mononuclear cells and the Plasmodium berghei ANKA experimental model of
      cerebral malaria were used to examine the role of CHI3L1 in severe malaria.
      RESULTS: In children presenting with falciparum malaria, CHI3L1 levels were
      increased in SMA and CM versus UM (p < 0.001). Among severe malaria cases, CHI3L1
      levels at presentation predicted subsequent death (area under receiver operating
      characteristic curve 0.84 [95% CI 0.76-0.92]) and in combination with other host
      biomarkers, predicted mortality with high sensitivity (100% [85.7-100]) and
      specificity (81.3% [71.3-88.3]). Plasmodium falciparum stimulated CHI3L1
      production by human peripheral blood mononuclear cells in vitro. CHI3L1 was
      increased in plasma and brain tissue in experimental cerebral malaria, but
      targeted Chi3l1 deletion did not alter cytokine production or survival in this
      model. CONCLUSIONS: These data suggest that plasma CHI3L1 measured at
      presentation correlates with malaria severity and predicts outcome in paediatric
      SMA and CM, but do not support a causal role for CHI3L1 in cerebral malaria
      pathobiology in the model tested.

PMID- 25047115
TI  - Effect of Ganoderma lucidum hydroalcoholic extract on insulin release in rat
      isolated pancreatic islets.
AB  - OBJECTIVE: Ganoderma Lucidum (G. Lucidum) has been suggested to increase serum
      insulin level. This study was undertaken to investigate its direct effect on the
      islets of Langerhans. MATERIAL AND METHODS: Male albino Wistar rats were
      anesthetized and the islets were isolated after digestion of the pancreas with
      collagenase. The islets were incubated for 60 min in Krebs bicarbonate buffer
      containing 3 or 10 mM glucose in the presence of hydroalcoholic extract of G.
      Lucidum (1 mg/ml), 3-isobutyl-1-methylxanthine (IBMX, 100 uM) or vehicle.
      RESULTS: Exposure of islets to the extract increased insulin secretion at basal
      (3 mM) glucose concentration. Increase of glucose concentration to 10 mM resulted
      in a significant increase in the rate of insulin secretion. While the IBMX could
      augment insulin release evoked by 10 mM glucose, the extract failed to modify it.
      CONCLUSION: Our results demonstrate that G. lucidum acts directly on the
      Langerhans islets to increase basal insulin release.

PMID- 25047117
TI  - Mourning the need for so many handovers.

PMID- 25047116
TI  - Polymicrogyria: pathology, fetal origins and mechanisms.
AB  - Polymicrogyria (PMG) is a complex cortical malformation which has so far defied
      any mechanistic or genetic explanation. Adopting a broad definition of an
      abnormally folded or festooned cerebral cortical neuronal ribbon, this review
      addresses the literature on PMG and the mechanisms of its development, as derived
      from the neuropathological study of many cases of human PMG, a large proportion
      in fetal life. This reveals the several processes which appear to be involved in
      the early stages of formation of polymicrogyric cortex. The most consistent
      feature of developing PMG is disruption of the brain surface with pial defects,
      over-migration of cells, thickening and reduplication of the pial collagen layers
      and increased leptomeningeal vascularity. Evidence from animal models is
      consistent with our observations and supports the notion that disturbance in the
      formation of the leptomeninges or loss of their normal signalling functions are
      potent contributors to cortical malformation. Other mechanisms which may lead to
      PMG include premature folding of the neuronal band, abnormal fusion of adjacent
      gyri and laminar necrosis of the developing cortex. The observation of PMG in
      association with other and better understood forms of brain malformation, such as
      cobblestone cortex, suggests mechanistic pathways for some forms of PMG. The role
      of altered physical properties of the thickened leptomeninges in exerting
      mechanical constraints on the developing cortex is also considered. 

PMID- 25047118
TI  - Development of pro-apoptotic peptides as potential therapy for peritoneal
      endometriosis.
AB  - Endometriosis is a common gynaecological disease associated with pelvic pain and
      infertility. Current treatments include oral contraceptives combined with
      nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which
      provide a temporary but not complete cure. Here we identify an endometriosis
      targeting peptide that is internalized by cells, designated z13, using phage
      display. As most endometriosis occurs on organ surfaces facing the peritoneum, we
      subtracted a phage display library with female mouse peritoneum tissue and
      selected phage clones by binding to human endometrial epithelial cells.
      Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated
      channel beta3, a sorting pathway protein. We then linked z13 with an apoptosis
      inducing peptide and with an endosome-escaping peptide. When these peptides were
      co-administered into the peritoneum of baboons with endometriosis, cells in
      lesions selectively underwent apoptosis with no effect on neighbouring organs.
      Thus, this study presents a strategy that could be useful to treat peritoneal
      endometriosis in humans. 

PMID- 25047119
TI  - Leptin increases TNF-alpha expression and production through phospholipase D1 in
      Raw 264.7 cells.
AB  - Epidemiological evidence suggests that obesity is associated with inflammation of
      the respiratory tract and the pathogenesis of asthma. The purpose of this study
      was to examine the role of phospholipase D1 (PLD1) in leptin-induced expression
      of the proinflammatory cytokine, tumor necrosis factor (TNF)-alpha, and to
      suggest a molecular link between obesity and respiratory tract inflammation. We
      investigated whether leptin, a typical adipocytokine, plays a role in the
      expression of TNF-alpha through increased PLD1 activity in Raw 264.7. Leptin
      enhanced the activity of PLD1 through activation of PLCgamma and Src, while PLD1
      siRNA decreased the leptin-induced expression and production of TNF-alpha. Leptin
      induced PLD activation was also inhibited by a PLCgamma inhibitor (PAO) and Src
      kinase inhibitor (PP2), indicating that PLCgamma and Src kinase are upstream
      activators of PLD1. Down-regulation of PLD1 also completely blocked activation of
      p70S6K, an activator of JNK. Leptin-induced expression of TNF-alpha was also
      prevented by inhibition of p70S6K and JNK. Taken together, these results indicate
      that PLD1 acts as an important regulator of leptin-induced expression of TNF
      alpha by participating in the PLCgamma/Src/PLD1/PA/p70S6K/JNK pathway. 

PMID- 25047120
TI  - Acceptability and feasibility of mifepristone medical abortion in the early first
      trimester in Azerbaijan.
AB  - OBJECTIVE: To examine the acceptability and feasibility of early medical abortion
      using mifepristone and misoprostol in Azerbaijan. METHODS: A total of 863 women
      in Baku and two regions of Azerbaijan who sought termination of gestations up to
      63 days were enrolled in the study. In the capital, women swallowed 200 mg
      mifepristone in the clinic and were given the option of taking 800 MUg
      misoprostol buccally either at the clinic or at home 24-48 hours later. In the
      regions, women were given the option of taking both drugs at home. Follow-up
      visits were to take place two weeks after mifepristone administration to
      determine abortion status. RESULTS: Seventy-four percent of women in the regions
      chose home administration of mifepristone, and 92% of women from all locations
      selected misoprostol home administration. Ninety-seven percent of women had
      complete abortions, and 97% were satisfied or very satisfied with the method. The
      vast majority of participants preferred medical abortion for a future procedure
      (96%). Nearly all women (98%) would recommend medical abortion for pregnancy
      termination to a friend. CONCLUSION: Mifepristone-misoprostol medical abortion
      with the option of home administration of both drugs is an acceptable and
      feasible option for women in Azerbaijan.

PMID- 25047121
TI  - The Breast Unit Update on advantages and the open issues.
AB  - Breast cancer is acknowledged as an international priority in health care. It is
      currently the most common cancer in women worldwide, with demographic trends
      indicating a continuous increase in incidence. In the World, it is estimated that
      by 2020 there will be approximately 2,000,000 new cases of breast cancer per
      year. The enormous burden placed by this disease both on the population and on
      health care systems explains the increasing efforts and resources that have been
      devoted over the years to the search for a systematic and optimized strategy in
      breast cancer diagnosis and treatment. Today, the Breast Unit model is identified
      as the gold-standard to ensure optimized patient-centered and research-based
      clinical services for breast cancer patients improving survival rates and
      patients' quality of life by a multidisciplinary approach in breast care. The
      present work reviews the lines of development of this multidisciplinary model of
      breast cancer treatment and analyzes the requirements of a high quality Breast
      Unit, its potential advantages and the many open issues that still require proper
      definition and implementation.

PMID- 25047122
TI  - Evidencing the existence of intrinsic half-metallicity and ferromagnetism in
      zigzag gallium sulfide nanoribbons.
AB  - The achievement of half-metallicity with ferromagnetic (FM) coupling has become a
      key technology for the development of one-dimensional (1D) nanoribbons for
      spintronic applications. Unfortunately, in previous studies, such a half
      metallicity always occurs upon certain external constraints. Here we, for the
      first time, demonstrate, via density functional theory (DFT), that the recent
      experimentally realized gallium sulfide nanoribbons (GaSNRs) can display an
      intrinsic half-metallic character with FM coupling, raised from Ga-4s, Ga-4p and
      S-3p states at the Ga-dominated edge. Furthermore, the novel half-metallic
      behavior with FM coupling here is rather robust, especially for GaSNRs with large
      width and thickness, and can be sustained to the room temperature. Thus, our
      results accidentally disclose a new 1D spin nanomaterial, which allows us to go
      beyond the current scope limited to the graphene, boron nitride (BN), zinc oxide
      (ZnO) and molybdenum sulfide (MoS2) nanoribbons, toward more realistic spintronic
      applications. 

PMID- 25047123
TI  - Pharmacodynamic change in plasma angiogenic proteins: a dose-escalation phase 1
      study of the multi-kinase inhibitor lenvatinib.
AB  - BACKGROUND: Lenvatinib (E7080), an oral multi-kinase inhibitor, has inhibitory
      action on tumor cell proliferation and tumor angiogenesis in preclinical models.
      We evaluated correlations between pharmacodynamic (PD) biomarkers with patient
      clinical outcomes in a lenvatinib phase 1 dose-escalation study. METHODS: Plasma
      angiogenic proteins were evaluated as potential PD biomarkers of response to
      lenvatinib in a dose-escalation phase 1 study. Lenvatinib was administered to 27
      patients by twice-daily dosing in 3-week cycles; 2 weeks of treatment followed by
      1 week of rest until discontinuation. Blood samples for plasma proteins were
      collected on days 1 (baseline), 8, and 15 of cycle 1, and days 1, 8, and 15 of
      cycle 2. Selected clinical outcomes, including tumor shrinkage and adverse events
      (AEs), were used for correlative analyses of pharmacokinetic parameters and PD
      biomarkers. RESULTS: Tumor shrinkage and changes in PD biomarkers (increased
      vascular endothelial growth factor [VEGF] and stromal cell-derived factor 1 alpha
      [SDF1alpha] levels and decreased soluble VEGF receptor 2 [sVEGFR2] levels)
      significantly correlated with increasing lenvatinib exposure. Observed changes in
      levels of VEGF, SDF1alpha, and sVEGFR2 were maintained on day 15 of cycle 1, but
      returned to baseline during the 1-week rest period, and similar changes were
      induced by reinstitution of treatment in cycle 2. The worst grades of
      hypertension, proteinuria, and fatigue were associated with changes in VEGF and
      HGF at day 8 of cycle 1. Maximum tumor shrinkage was correlated with increased
      SDF1alpha levels. Decreased sVEGFR2 level was also correlated with tumor
      shrinkage and frequency of hypertension, proteinuria, and fatigue. Tumor
      shrinkage significantly correlated with the worst grade of proteinuria, but not
      with hypertension or fatigue. CONCLUSION: PD biomarker changes observed in plasma
      angiogenic proteins are correlated with lenvatinib-induced tumor shrinkage and
      AEs. Our findings warrant further assessment of plasma proteins associated with
      angiogenesis as potential biomarkers of lenvatinib activity. TRIAL REGISTRATION:
      ClinicalTrial.gov: NCT00280397 (January 20, 2006).

PMID- 25047124
TI  - A novel method to establish a rat ED model using internal iliac artery ligation
      combined with hyperlipidemia.
AB  - OBJECTIVE: To investigate a novel method, namely using bilateral internal iliac
      artery ligation combined with a high-fat diet (BCH), for establishing a rat model
      of erectile dysfunction (ED) that, compared to classical approaches, more closely
      mimics the chronic pathophysiology of human ED after acute ischemic insult.
      MATERIALS AND METHODS: Forty 4-month-old male Sprague Dawley rats were randomly
      placed into five groups (n = 8 per group): normal control (NC), bilateral
      internal iliac artery ligation (BIIAL), high-fat diet (HFD), BCH, and mock
      surgery (MS). All rats were induced for 12 weeks. Copulatory behavior,
      intracavernosal pressure (ICP), ICP/mean arterial pressure, hematoxylin-eosin
      staining, Masson's trichrome staining, serum lipid levels, and endothelial and
      neuronal nitric oxide synthase immunohistochemical staining of the cavernous
      smooth muscle and endothelium were assessed. Data were analyzed by SAS 8.0 for
      Windows. RESULTS: Serum total cholesterol and triglyceride levels were
      significantly higher in the HFD and BCH groups than the NC and MS groups. High
      density lipoprotein levels were significantly lower in the HFD and BCH groups
      than the NC and MS groups. The ICP values and mount and intromission numbers were
      significantly lower in the BIIAL, HFD, and BCH groups than in the NC and MS
      groups. ICP was significantly lower in the BCH group than in the BIIAL and HFD
      groups. Cavernous smooth muscle and endothelial damage increased in the HFD and
      BCH groups. Cavernous smooth muscle to collagen ratio, nNOS and eNOS staining
      decreased significantly in the BIIAL, HFD, and BCH groups compared to the NC and
      MS groups. CONCLUSIONS: The novel BCH model mimics the chronic pathophysiology of
      ED in humans and avoids the drawbacks of traditional ED models.

PMID- 25047125
TI  - Identification and characterisation of Aedes aegypti aldehyde dehydrogenases
      involved in pyrethroid metabolism.
AB  - BACKGROUND: Pyrethroid insecticides, especially permethrin and deltamethrin, have
      been used extensively worldwide for mosquito control. However, insecticide
      resistance can spread through a population very rapidly under strong selection
      pressure from insecticide use. The upregulation of aldehyde dehydrogenase (ALDH)
      has been reported upon pyrethroid treatment. In Aedes aegypti, the increase in
      ALDH activity against the hydrolytic product of pyrethroid has been observed in
      DDT/permethrin-resistant strains. The objective of this study was to identify the
      role of individual ALDHs involved in pyrethroid metabolism. METHODOLOGY/PRINCIPAL
      FINDINGS: Three ALDHs were identified; two of these, ALDH9948 and ALDH14080, were
      upregulated in terms of both mRNA and protein levels in a DDT/pyrethroid
      resistant strain of Ae. aegypti. Recombinant ALDH9948 and ALDH14080 exhibited
      oxidase activities to catalyse the oxidation of a permethrin intermediate,
      phenoxybenzyl aldehyde (PBald), to phenoxybenzoic acid (PBacid).
      CONCLUSIONS/SIGNIFICANCE: ALDHs have been identified in association with
      permethrin resistance in Ae. aegypti. Characterisation of recombinant ALDHs
      confirmed the role of this protein in pyrethroid metabolism. Understanding the
      biochemical and molecular mechanisms of pyrethroid resistance provides
      information for improving vector control strategies.

PMID- 25047126
TI  - Prognostic value of total atrial conduction time measured with tissue Doppler
      imaging to predict the maintenance of sinus rhythm after external electrical
      cardioversion of persistent atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia,
      with a high recurrence rate, especially during the first months after
      cardioversion (CV). Few parameters have been evaluated as predictors for the
      maintenance of sinus rhythm (SR), with limited results. Recently total atrial
      conduction time (TACT) has been proposed as independent predictor of AF
      recurrence. The aim of this study was to investigate the prognostic value of
      TACT, measured using PA-TDI duration, to predict 1-year maintenance of restored
      SR after electrical CV. METHODS AND RESULTS: In a population of 104 patients (58
      male, aged 70 +/- 9) with persistent AF, submitted to external electrical CV, we
      performed a complete echocardiogram after restoring SR. The TACT was estimated by
      measuring the time delay between the onset of the P-wave in lead II of the
      surface electrocardiogram and the peak A'-wave on the tissue Doppler imaging
      (TDI) tracing of the left atrial lateral wall (so-called PA-TDI duration). After
      a mean follow-up of 14 +/- 2 months, 34 (33%) patients had recurrent AF, whereas
      70 (67%) patients maintained SR. At multivariate analysis only PA-TDI was
      identified as independent predictor of AF recurrence (HR 1.04; 95% CI 1.03-1.06;
      P < 0.001). Receiver operator characteristics curve analyses demonstrated a high
      degree of discrimination (area under the curve 0.923); with a cut point of 152
      msec, we obtain a good diagnostic accuracy (sensitivity 91%, specificity 87%).
      CONCLUSION: The TACT using TDI is an independent predictor of AF recurrence and
      can be used to predict the maintenance of SR after external electrical CV.

PMID- 25047127
TI  - Fullerene van der Waals oligomers as electron traps.
AB  - Density functional theory calculations indicate that van der Waals fullerene
      dimers and larger oligomers can form interstitial electron traps in which the
      electrons are even more strongly bound than in isolated fullerene radical anions.
      The fullerenes behave like "super atoms", and the interstitial electron traps
      represent one-electron intermolecular sigma-bonds. Spectroelectrochemical
      measurements on a bis-fullerene-substituted peptide provide experimental support.
      The proposed deep electron traps are relevant for all organic electronics
      applications in which non-covalently linked fullerenes in van der Waals contact
      with one another serve as n-type semiconductors. 

PMID- 25047129
TI  - Quantum dots still shining strong 30 years on.

PMID- 25047128
TI  - Quantification of methylated selenium, sulfur, and arsenic in the environment.
AB  - Biomethylation and volatilization of trace elements may contribute to their
      redistribution in the environment. However, quantification of volatile,
      methylated species in the environment is complicated by a lack of straightforward
      and field-deployable air sampling methods that preserve element speciation. This
      paper presents a robust and versatile gas trapping method for the simultaneous
      preconcentration of volatile selenium (Se), sulfur (S), and arsenic (As) species.
      Using HPLC-HR-ICP-MS and ESI-MS/MS analyses, we demonstrate that volatile Se and
      S species efficiently transform into specific non-volatile compounds during
      trapping, which enables the deduction of the original gaseous speciation. With
      minor adaptations, the presented HPLC-HR-ICP-MS method also allows for the
      quantification of 13 non-volatile methylated species and oxyanions of Se, S, and
      As in natural waters. Application of these methods in a peatland indicated that,
      at the selected sites, fluxes varied between 190-210 ng Se.m(-2).d(-1), 90-270 ng
      As.m(-2).d(-1), and 4-14 ug S.m(-2).d(-1), and contained at least 70% methylated
      Se and S species. In the surface water, methylated species were particularly
      abundant for As (>50% of total As). Our results indicate that methylation plays a
      significant role in the biogeochemical cycles of these elements.

PMID- 25047132
TI  - Elicitin-like proteins Oli-D1 and Oli-D2 from Pythium oligandrum trigger
      hypersensitive response in Nicotiana benthamiana and induce resistance against
      Botrytis cinerea in tomato.
AB  - The biocontrol agent Pythium oligandrum and its elicitin-like proteins
      oligandrins have been shown to induce disease resistance in a range of plants. In
      the present study, the ability of two oligandrins, Oli-D1 and Oli-D2, to induce
      an immune response and the possible molecular mechanism regulating the defence
      responses in Nicotiana benthamiana and tomato were investigated. Infiltration of
      recombinant Oli-D1 and Oli-D2 proteins induced a typical immune response in N.
      benthamiana including the induction of a hypersensitive response (HR),
      accumulation of reactive oxygen species and production of autofluorescence.
      Agrobacterium-mediated transient expression assays revealed that full-length Oli
      D1 and Oli-D2 were required for full HR-inducing activity in N. benthamiana, and
      virus-induced gene silencing-mediated knockdown of some of the signalling
      regulatory genes demonstrated that NbSGT1 and NbNPR1 were required for Oli-D1 and
      Oli-D2 to induce HR in N. benthamiana. Subcellular localization analyses
      indicated that both Oli-D1 and Oli-D2 were targeted to the plasma membrane of N.
      benthamiana. When infiltrated or transiently expressed in leaves, Oli-D1 and Oli
      D2 induced resistance against Botrytis cinerea in tomato and activated the
      expression of a set of genes involved in the jasmonic acid/ethylene (JA/ET)
      mediated signalling pathway. Our results demonstrate that Oli-D1 and Oli-D2 are
      effective elicitors capable of inducing immune responses in plants, probably
      through the JA/ET-mediated signalling pathway, and that both Oli-D1 and Oli-D2
      have potential for the development of bioactive formulae for crop disease control
      in practice.

PMID- 25047131
TI  - Twenty years of acanthamoeba diagnostics in Austria.
AB  - Acanthamoebae are the causative agents of an often seriously progressing
      keratitis (AK) occurring predominantly in contact lens wearers and can cause
      several disseminating infections potentially resulting in granulomatous amoebic
      encephalitis (GAE) in the immunocompromised host. Our institution is the Austrian
      reference laboratory for Acanthamoeba diagnostics and the aim of this study was
      to give an overview of proven cases of Acanthamoeba infections in Austria during
      the past 20 yr. All samples of patients with suspected AK or GAE were screened
      for Acanthamoeba spp. by culture and/or PCR and the detected amoebae were
      genotyped. Altogether, 154 cases of AK and three cases of GAE were diagnosed. Age
      of the AK patients ranged from 8 to 82 yr (mean 37.8) and 58% of the patients
      were female. Approximately 89% of the AK patients were contact lens wearers,
      almost all cases were unilateral and 19% of the patients required a keratoplasty.
      Age of the GAE patients ranged from 2 to 25 yr (mean 14.7), all were HIV
      negative, but two were severely immunosuppressed at the time of diagnosis. The
      predominant genotype in the AK cases was T4, other genotypes found were T3, T5,
      T6, T10 and T11. The three GAE cases involved genotypes T2, T4 and T5. 

PMID- 25047133
TI  - Current status of robotic laparoendoscopic single-site partial nephrectomy.
AB  - Robotic laparoendoscopic single-site partial nephrectomy is increasingly carried
      out in an attempt to improve the cosmetic outcome of minimally-invasive
      procedures. However, the actual role of this novel technique remains to be
      determined. The present article reviews evidence and examines updates of robotic
      laparoendoscopic single-site partial nephrectomy outcomes reported in more
      contemporary studies. A comprehensive online systematic search of PubMed, Scopus
      and Web of Science databases according to Preferred Reporting Items for
      Systematic Reviews and Meta-analyses criteria recommendations was carried out in
      January 2014, identifying data from 2008 to 2014 regarding robotic
      laparoendoscopic single-site partial nephrectomy. The majority of medical
      evidence to date is based on case reports or retrospective studies. Current
      studies show that robotic laparoendoscopic single-site partial nephrectomy is a
      feasible procedure carried out in an acceptable length of operative time, and
      resulting in a desirable cosmetic outcome and less postoperative pain. However,
      comparable studies show that robotic laparoendoscopic single-site partial
      nephrectomy is inferior to the conventional approach, especially with regard to
      warm ischemia time. Furthermore, the numerous limitations that exist with the
      utilization of the current commercial single-site devices make robotic
      laparoendoscopic single-site PN more challenging and more complicated for
      surgeons compared with conventional procedures. Further significant improvements,
      along with more studies, are required in order to develop the ideal robotic
      laparoendoscopic single-site robotic platform and overcome the current
      limitations. For the time being, robotic laparoendoscopic single-site partial
      nephrectomy procedures could be applicable in patients with low tumor size and
      complexity, and should not be routinely applied in all cases. 

PMID- 25047134
TI  - Same-day diagnosis based on histology for women suspected of breast cancer: high
      diagnostic accuracy and favorable impact on the patient.
AB  - BACKGROUND: Same-day diagnosis based on histology is increasingly being offered
      to patients suspected of breast cancer. We evaluated to which extent same-day
      diagnosis affected diagnostic accuracy and patients' anxiety levels during the
      diagnostic phase. PATIENTS AND METHODS: All 759 women referred for same-day
      evaluation of suspicious breast lesions between November 2011-March 2013 were
      included. Diagnostic accuracy was assessed by linking all patients to the
      national pathology database to identify diagnostic discrepancies, in which case
      slides were reviewed. Patients' anxiety was measured in 127 patients by the State
      Trait and Anxiety Inventory on six moments during the diagnostic workup and
      changes over time (< = 1 week) were analyzed by mixed effect models. RESULTS:
      Core-needle biopsy was indicated in 374/759 patients (49.3%) and in 205/759 (27%)
      patients, invasive or in situ cancer was found. Final diagnosis on the same day
      was provided for 606/759 (79.8%) patients. Overall, 3/759 (0.4%) discordant
      findings were identified. Anxiety levels decreased significantly over time from
      45.2 to 30.0 (P = <0.001). Anxiety levels decreased from 44.4 to 25.9 (P =
      <0.001) for patients with benign disease, and remained unchanged for patients
      diagnosed with malignancies (48.6 to 46.7, P = 0.933). Time trends in anxiety
      were not affected by other patient or disease characteristics like age, education
      level or (family) history of breast cancer. CONCLUSION: Same-day histological
      diagnosis is feasible in the vast majority of patients, without impairing
      diagnostic accuracy. Patients' anxiety rapidly decreased in patients with a
      benign diagnosis and remained constant in patients with malignancy.

PMID- 25047136
TI  - Direct carbocyclizations of benzoic acids: catalyst-controlled synthesis of
      cyclic ketones and the development of tandem aHH (acyl Heck-Heck) reactions.
AB  - The formation of exo-methylene indanones and indenones from simple ortho-allyl
      benzoic acid derivatives has been developed. Selective formation of the indanone
      or indenone products in these reactions is controlled by choice of ancillary
      ligand. This new process has a low environmental footprint as the products are
      formed in high yields using low catalyst loadings, while the only stoichiometric
      chemical waste generated from the reactants in the transformation is acetic acid.
      The conversion of the active cyclization catalyst into the Hermman-Beller
      palladacycle was exploited in a one-pot tandem acyl Heck-Heck (aHH) reaction, and
      utilized in the synthesis of donepezil. 

PMID- 25047135
TI  - Characterization and immobilization on nickel-chelated Sepharose of a glutamate
      decarboxylase A from Lactobacillus brevis BH2 and its application for production
      of GABA.
AB  - A gene encoding glutamate decarboxylase A (GadA) from Lactobacillus brevis BH2
      was expressed in a His-tagged form in Escherichia coli cells, and recombinant
      protein exists as a homodimer consisting of identical subunits of 53 kDa. GadA
      was absolutely dependent on the ammonium sulfate concentration for catalytic
      activity and secondary structure formation. GadA was immobilized on the metal
      affinity resin with an immobilization yield of 95.8%. The pH optima of the
      immobilized enzyme were identical with those of the free enzyme. However, the
      optimum temperature for immobilized enzyme was 5  degrees C higher than that for
      the free enzyme. The immobilized GadA retained its relative activity of 41% after
      30 reuses of reaction within 30 days and exhibited a half-life of 19 cycles
      within 19 days. A packed-bed bioreactor with immobilized GadA showed a maximum
      yield of 97.8% GABA from 50 mM l-glutamate in a flow-through system under
      conditions of pH 4.0 and 55  degrees C.

PMID- 25047137
TI  - Medication adherence in adolescents in current practice: community pharmacy
      staff's opinions.
AB  - OBJECTIVE: To explore pharmacy staff's perspectives regarding medication use
      behaviour in adolescent patients. METHODS: Structured face-to-face interviews
      were conducted with 170 community pharmacy staff members. KEY FINDINGS:
      Medication-related problems in adolescents had been experienced by 80
      respondents; non-adherence was frequently mentioned (n = 73). An important reason
      for medication-related problems in adolescents not being recognised was that
      prescriptions are often collected by the parents (with or without the teenager).
      Solutions suggested by the interviewees to improve adolescents' medication use
      behaviour included (improving) counselling with emphasis on necessity/benefits of
      medication (n = 130) and more direct contact with adolescents instead of
      parent(s) (n = 77). Use of digital media for educational purposes or reminder
      services was suggested to support medication use (n = 67). CONCLUSIONS: Almost
      half of pharmacy staff experienced problems related to medication use in
      adolescents. Pharmacy staff see a primary role for counselling on the benefits of
      therapy but foresee difficulties in obtaining direct contact with adolescents.
      Use of new media could be useful.

PMID- 25047138
TI  - Glucagon-like peptide 1 receptor agonist therapy is more efficacious than insulin
      glargine for poorly controlled type 2 diabetes: A systematic review and meta
      analysis.
AB  - BACKGROUND: The aim of the present study was to compare the reported efficacy and
      safety of glucagon-like peptide-l receptor agonist (GLP-1RA) and insulin glargine
      (IGlar) for poorly controlled type 2 diabetes. METHODS: Medline, EMBASE, Cochrane
      Library, and clinicaltrials.gov were carried out. References and cited papers of
      relevant articles were also checked. RESULTS: Seven trials met the inclusion
      criteria. GLP-1RA showed equivalent or superior efficacy to IGlar for reducing
      hemoglobin A1c (HbA1c), with a greater proportion of patients achieving HbAlc<7%.
      GLP-1RA also favored decreased body weight, total cholesterol (TC), low-density
      lipoprotein (LDL), and systolic blood pressure (SBP). Serious adverse events were
      uncommon and not significantly different. More patients taking GLP-1RA
      experienced gastrointestinal complications: nausea, diarrhea, and vomiting.
      Severe hypoglycemia events were rare, and minor hypoglycemia was less common for
      GLP-1RA. CONCLUSIONS: GLP-1RA showed greater efficacy compared to IGlar for type
      2 diabetes, and it may also prove beneficial for other diabetes-associated
      characteristics, including obesity, hypertension, and hyperlipidemia.

PMID- 25047139
TI  - Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax
      (ABT-263), a dual inhibitor of Bcl-2 and Bcl-XL , in patients with cancer.
AB  - WHAT IS KNOWN AND OBJECTIVE: Navitoclax, a first-in-class small molecule Bcl-2
      family inhibitor, is metabolized in vitro by the hepatic microsomal cytochrome
      P450 (CYP) enzymes CYP3A4. Drugs that affect CYP3A4 may therefore have an impact
      on the pharmacological profile of navitoclax. This study evaluated the effects of
      co-administration of a potent CYP3A4 inducer rifampin on the pharmacokinetic and
      safety profiles of navitoclax. METHODS: This open-label, fixed-sequence, 2-period
      study was performed in twelve subjects with non-haematologic or haematologic
      malignancy that was relapsed or refractory to standard therapy. A 7-day washout
      period separated the two treatment periods. On Study Day 1 and Day 8, subjects
      received a single 250 mg oral dose of navitoclax. Rifampin 600 mg was
      administrated once daily (QD) on Study Day 4 through Day 10. Blood samples for
      navitoclax assay were collected prior to dosing (0 h) and at a series of time
      points through 72 h after dosing on Study Day 1 and Day 8. RESULTS AND
      DISCUSSION: Co-administration of a single 250 mg dose of navitoclax with 600 mg
      QD doses of rifampin had a negligible effect on the maximum plasma concentration
      (Cmax ) of navitoclax [ratio of geometric least square means: 0.84 (90% CI: 0.61
      1.16)] but moderately decreased the area under the plasma concentration-time
      curve (AUC) of navitoclax [ratio of geometric least square means: 0.59 (90% CI:
      0.44-0.80)]. Rifampin did not affect the half-life of navitoclax. Co
      administration of rifampin did not appear to significantly change the safety
      profile of navitoclax in the limited number of patients evaluated in this study.
      WHAT IS NEW AND CONCLUSION: Co-administration navitoclax with rifampin moderately
      decreased navitoclax AUC, which could be partly due to the induction effect of
      rifampin on CYP3A4. Further assessment on the mechanism of drug interaction is
      warranted.

PMID- 25047140
TI  - High total hospitalization cost but low cost of imaging studies in recurrent
      acute ischemic stroke patients.
AB  - BACKGROUND: Due to the high risk and severity of recurrence after stroke attack,
      recurrence is a major reason contributing to the disease burden. This study aims
      to determine whether recurrence is a significant contributor of hospitalization
      cost in items for ischemic stroke patients. METHODS: This study assessed acute
      ischemic stroke patients admitted to an academic medical center in 2003 through
      2009. The t-test and Chi-square tests were used to compare first-ever and
      recurrent ischemic stroke groups in terms of total and categorized
      hospitalization cost, and multiple regression was performed to assess the
      influence of stroke recurrence. RESULTS: Recurrent ischemic strokes were
      associated with higher total cost, but examination cost showed no difference
      between the two groups. The recurrent stroke group showed higher laboratory but
      lower imaging cost. Of imaging studies, there was no significant difference in
      computed tomography scan cost while the first-ever stroke group spent more on
      magnetic resonance imaging and sonography. Controlling for other influential
      factors, recurrence was discovered to be a significant factor in lowering
      examination cost. CONCLUSIONS: The findings of stroke recurrence in lowering
      examination cost could be explained from two perspectives, different clinical
      patterns of healthcare utilization and patients' economic status in recurrent
      stroke.

PMID- 25047142
TI  - Headspace-gas chromatographic-mass spectrometric analysis of South American
      commercial solvents and their use in the illicit conversion of cocaine base to
      cocaine hydrochloride.
AB  - This study presents data that establish the makeup of solvents utilized in
      illicit cocaine hydrochloride production, as determined via the identification of
      the occluded solvents in the crystal matrix of the final product. The occluded
      solvent ratios can differ dramatically from the ratios of the original processing
      solvents. Additionally, the presented data suggest the diversion of commercial
      solvents to illicit cocaine hydrochloride laboratories. Thirty-five commercial
      solvents were obtained from five chemical manufacturing companies in South
      America. Each solvent was qualitatively and quantitatively analyzed using static
      headspace-gas chromatography-mass spectrometry (HS-GC-MS). After obtaining the
      chemical profile for each commercial solvent, solvents and/or solvent mixtures
      were prepared to be comparable in composition to several of the commercial
      products. Over 90 individual batches of cocaine hydrochloride were prepared from
      cocaine base using these solvents or solvent mixtures, which match those most
      commonly employed in clandestine laboratories. Additionally, a number of unique
      manufacturing by-products produced from processing solvents were identified, and
      their significance is discussed. 

PMID- 25047143
TI  - Consensus guidelines for enhanced recovery after gastrectomy: Enhanced Recovery
      After Surgery (ERAS(r)) Society recommendations.
AB  - BACKGROUND: Application of evidence-based perioperative care protocols reduces
      complication rates, accelerates recovery and shortens hospital stay. Presently,
      there are no comprehensive guidelines for perioperative care for gastrectomy.
      METHODS: An international working group within the Enhanced Recovery After
      Surgery (ERAS(r)) Society assembled an evidence-based comprehensive framework for
      optimal perioperative care for patients undergoing gastrectomy. Data were
      retrieved from standard databases and personal archives. Evidence and
      recommendations were classified according to the Grading of Recommendations,
      Assessment, Development and Evaluation (GRADE) system and were discussed until
      consensus was reached within the group. The quality of evidence was rated 'high',
      'moderate', 'low' or 'very low'. Recommendations were graded as 'strong' or
      'weak'. RESULTS: The available evidence has been summarized and recommendations
      are given for 25 items, eight of which contain procedure-specific evidence. The
      quality of evidence varies substantially and further research is needed for many
      issues to improve the strength of evidence and grade of recommendations.
      CONCLUSION: The present evidence-based framework provides comprehensive advice on
      optimal perioperative care for the patient undergoing gastrectomy and facilitates
      multi-institutional prospective cohort registries and adequately powered
      randomized trials for further research.

PMID- 25047144
TI  - Factors associated with pain experience outcome in knee osteoarthritis.
AB  - OBJECTIVE: Few strategies to improve pain outcome in knee osteoarthritis (OA)
      exist in part because how best to evaluate pain over the long term is unclear.
      Our objectives were to determine the frequency of a good pain experience outcome
      based on previously formulated OA pain stages and test the hypothesis that less
      depression and pain catastrophizing and greater self-efficacy and social support
      are each associated with greater likelihood of a good outcome. METHODS: Study
      participants, all with knee OA, reported pain stage at baseline and 2 years.
      Baseline assessments utilized the Geriatric Depression Scale, Pain
      Catastrophizing Scale, Arthritis Self-Efficacy Scale, and Medical Outcomes Study
      social support survey. Using pain experience stages, good outcome was defined as
      persistence in or movement to no pain or stage 1 (predictable pain, known
      trigger) at 2 years. A multivariable logistic regression model was developed to
      identify independent predictors of a good outcome. RESULTS: Of 212 participants,
      136 (64%) had a good pain outcome and 76 (36%) a poor pain outcome. In
      multivariable analysis, higher self-efficacy was associated with a significantly
      higher likelihood of good outcome (adjusted odds ratio [OR] 1.14 [95% confidence
      interval (95% CI) 1.04-1.24]); higher pain catastrophizing was associated with a
      significantly lower likelihood of good outcome (adjusted OR 0.88 [95% CI 0.83
      0.94]). CONCLUSION: This stage-based measure provides a meaningful and
      interpretable means to assess pain outcome in knee OA. The odds of a good 2-year
      outcome in knee OA were lower in persons with greater pain catastrophizing and
      higher in persons with greater self-efficacy. Targeting these factors may help to
      improve pain outcome in knee OA.

PMID- 25047147
TI  - Diffusive and rotational dynamics of condensed n-H2 confined in MCM-41.
AB  - In this paper, we report an inelastic neutron scattering study of liquid and
      solid n-H2 confined within MCM-41. This is a high surface area, mesoporous silica
      glass with a narrow pore size distribution centered at 3.5 nm. The scattering
      data provides information about the diffusive and rotational dynamics of the
      adsorbed n-H2 at low temperatures. In the liquid state, the neutron scattering
      data demonstrates that only a fraction of the adsorbed o-H2 is mobile on the
      picosecond time scale. This mobile fraction undergoes liquid-like jump diffusion,
      and values for the residence time tau and effective mean-squared displacement
      <u(2)> are reported as a function of pore filling. In the solid state, the
      rotational energy levels of adsorbed H2 are strongly perturbed from their free
      quantum rotor behavior in the bulk solid. The underlying orientational potential
      of the hindered rotors is due to the surface roughness and heterogeneity of the
      MCM-41 pore walls. This potential is compared to the hindering potential of other
      porous silicas, such as Vycor. Strong selective adsorption makes the interfacial
      layer rich in o-H2, leaving the inner core volume consisting of a depleted
      mixture of o-H2 and p-H2. 

PMID- 25047146
TI  - hTERT- and hCTLA4Ig-expressing human bone marrow-derived mesenchymal stem cells:
      in vitro and in vivo characterization and osteogenic differentiation.
AB  - Multipotent mesenchymal stem cells (MSCs) are commonly used as seed cells in
      studies of tissue engineering and regenerative medicine but their clinical
      application is limited, due to insufficient numbers of autogeneic MSCs, immune
      rejection of allogeneic MSCs and replicative senescence. We constructed two gene
      expression vectors for transfection of the human telomerase reverse transcriptase
      (hTERT) and cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4Ig) genes into
      human bone marrow-derived stem cells (hBMSCs). Successful transfection of both
      genes generated hTERT-CTLA4Ig hBMSCs that expressed both telomerase (shown by
      immunohistochemistry and a TRAPeze assay) and CTLA4Ig (demonstrated by
      immunocytochemistry and western blotting) without apparent mutual interference.
      Both hTERT BMSCs (92 population doublings) and hTERT-CTLA4Ig hBMSCs (60
      population doublings) had an extended lifespan compared with hBMSCs (18
      population doublings). Cell cycle analysis revealed that, compared with hBMSCs, a
      lower proportion of hTERT hBMSCs were in G0 /G1 phase but a higher proportion
      were in S phase; compared with hTERT hBMSCs, a higher proportion of hTERT-CTLA4Ig
      hBMSCs were in G0 /G1 phase, while a lower proportion were in S and G2 /M phases.
      hTERT-CTLA4Ig hBMSCs retained their capacity for osteogenic differentiation in
      vitro, shown by the detection of hydroxyapatite mineral deposition (labelled
      tetracycline fluorescence staining), calcareous nodules (alizarin red S
      staining), alkaline phosphatase (calcium-cobalt method) and osteocalcin
      (immunocytochemistry). Furthermore, subcutaneous transplantation of hTERT-CTLA4Ig
      hBMSCs in a rat xenotransplantation model resulted in the successful generation
      of bone-like tissue, confirmed using radiography and histological assessment. We
      propose that allogeneic hTERT-CTLA4Ig hBMSCs may be ideal seed cells for bone
      tissue engineering. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25047145
TI  - Use of cartilage derived from murine induced pluripotent stem cells for
      osteoarthritis drug screening.
AB  - OBJECTIVE: The discovery of novel disease-modifying drugs for osteoarthritis (OA)
      is limited by the lack of adequate genetically defined cartilage tissues for
      application in high-throughput screening systems. We addressed this need by
      synthesizing cartilage from induced pluripotent stem cells (iPSCs) to establish
      and validate an in vitro model of OA. METHODS: Native or iPSC-derived mouse
      cartilage samples were treated with the cytokine interleukin-1alpha (IL-1alpha)
      for 3 days to model the inflammatory environment of OA. The biochemical content,
      mechanical properties, and gene expression of the resulting tissues were assayed.
      In addition, the inflammatory and catabolic environment of the media was
      assessed. To establish high-throughput capability, we used a 96-well plate format
      and conducted a screen of previously identified candidate OA drugs.
      Glycosaminoglycan (GAG) release into the medium was used as the primary output
      for screening. RESULTS: Treatment of iPSC-derived or native cartilage with IL
      1alpha induced characteristic features of OA in a rapid and dose-dependent
      manner. In addition to the loss of GAGs and tissue mechanical properties, IL
      1alpha treatment induced the expression of matrix metalloproteinases and
      increased the production of the inflammatory mediators nitric oxide and
      prostaglandin E2 . In the high-throughput screen validation, all candidate OA
      therapeutic agents provided some benefit, but only the NF-kappaB inhibitor SC514
      effectively reduced cartilage loss in response to IL-1alpha. CONCLUSION: This
      work demonstrates the utility of iPSCs for studying cartilage pathology and
      provides a platform for identifying novel, patient-specific therapeutic agents
      that prevent cartilage degradation and modify the course of OA development.

PMID- 25047148
TI  - Asymmetric hydroxylative phenol dearomatization promoted by chiral binaphthylic
      and biphenylic iodanes.
AB  - The long-standing quest for chiral hypervalent organoiodine compounds (i.e.,
      iodanes) as metal-free reagents for asymmetric synthesis continues. Although
      remarkable progress has recently been made in organoiodine-catalyzed reactions
      using a terminal oxidant in stoichiometric amounts, there is still a significant
      need for "flaskable" chiral iodane reagents. Herein, we describe the synthesis of
      new iodobinaphthyls and iodobiphenyls, their successful and selective DMDO
      mediated oxidation into either lambda(3)- or lambda(5)-iodanes, and the
      evaluation of their capacity to promote asymmetric hydroxylative phenol
      dearomatization (HPD) reactions. Most notably, a C2-symmetrical biphenylic
      lambda(5)-iodane promoted the HPD-induced conversion of the monoterpene thymol
      into the corresponding ortho-quinol-based [4+2] cyclodimer (i.e., bis(thymol))
      with enantiomeric excesses of up to 94%.

PMID- 25047150
TI  - Circulating leptin levels are associated with physical activity or physical
      fitness in Japanese.
AB  - OBJECTIVE: The aim of this study was to evaluate the link between circulating
      leptin levels and physical activity and/or physical fitness in apparently healthy
      Japanese. METHODS: A total of 85 men and 111 women who were not taking any
      medication were enrolled in this cross-sectional study. Circulating leptin
      levels, physical activity measured by tri-axial accelerometers and peak oxygen
      uptake were evaluated. We also assessed anthropometric data, blood pressure,
      blood examinations and energy intake. RESULTS: Circulating leptin levels were 3.2
      +/- 2.3 ng/mL in men and 5.9 +/- 3.8 ng/mL in women. Circulating leptin levels
      were significantly and positively correlated with body weight, body mass index,
      abdominal circumference, insulin and the homeostasis model assessment index, and
      significantly and negatively correlated with peak oxygen uptake in both sexes.
      Stepwise multiple regression showed that peak oxygen uptake in men and physical
      activity evaluated by Sigma[metabolic equivalents h per week(METs h/w)]. in women
      were determinant factors for circulating leptin levels after adjusting for
      confounding factors.

PMID- 25047151
TI  - The influence of the substituent position in monocarboxymethyl-gamma
      cyclodextrins on enantioselectivity in capillary electrophoresis.
AB  - Three newly synthesized chiral selectors, namely, 2(I)-O-, 3(I)-O-, and 6(I)-O
      carboxymethyl-gamma-cyclodextrin, native gamma-cyclodextrin, and commercially
      available carboxymethylated gamma-cyclodextrin with degree of substitution of 3-6
      were used as additives in a background electrolyte composed of phosphate buffer
      at 20 mmol/L concentration and pH 2.5. This system was used for the analysis of
      several biologically significant low-molecular-mass chiral compounds by capillary
      electrophoresis. The results confirmed that the position of carboxymethyl group
      influences the enantioseparation efficiency of all the studied analytes. The 2(I)
      O- and 3(I)-O- regioisomers provide a significantly better resolution than native
      gamma-cyclodextrin, while the 6(I)-O-regioisomer gives only a slightly better
      enantioseparation than native gamma-cyclodextrin. The application of gamma
      cyclodextrin possessing higher number of carboxymethyl groups led to the best
      resolution for the majority of the compounds analyzed.

PMID- 25047152
TI  - Effects of sertraline on executive function and quality of life in patients with
      advanced cancer.
AB  - BACKGROUND: The aim of this study was to investigate effects of the
      antidepressant sertraline on executive function and quality of life in patients
      with advanced cancer. MATERIAL/METHODS: We assigned 122 patients with stage III
      or IV cancer to the depressed group (DG, n=86) or the non-depressed group (NG,
      n=36). All subjects were given supportive treatment and patients in the DG
      received additional antidepressant treatment. RESULTS: There were significant
      differences in total scores of the Hamilton anxiety scale (HAMA) and the Hamilton
      depression scale (HAMD), performance in the Wisconsin card sorting test, and SF
      36 domains. After antidepressant treatment, the level of depression and anxiety
      decreased significantly in the DG, but was still significantly higher than in the
      NG. Low executive function was enhanced in the DG, but a worsening executive
      function was found in total errors in the NG (-2.3+/-3.8) (P<0.05). The
      dimensions of SF-36 in physical functioning (PF), role limitations-physical (RP),
      bodily pain (BP), general health (GH), vitality (VT), social functioning (SF),
      role limitations-emotional (RE), and mental health (MH) were decreased
      significantly at baseline in the DG compared to the NG (P<0.01). After 12-week
      Sertraline treatment, improvement in the DG in factors VT, SF, RE, and MH were
      more powerful than in the NG (P<0.05). HAMA, HAMD, and VAS scores and tumor stage
      were significantly correlated to any one dimension of quality of life.
      CONCLUSIONS: Depression is an important cause of decreased quality of life and
      executive function in patients with advanced cancer. The antidepressant
      sertraline can improve the executive function and quality of life, which may be
      helpful in the clinical practice of cancer treatment.

PMID- 25047153
TI  - Good's syndrome presenting with recurrent giardiasis".

PMID- 25047154
TI  - Adequate patient's outcome achieved with short immunoglobulin replacement
      intervals in severe antibody deficiencies.
AB  - PURPOSE: The optimal immune globulin replacement dosages required over time to
      minimize infection risks in patients with Primary Antibody Deficiencies are not
      definitely established. As with many interventions, there may be specific
      subgroups of patients who are more likely to benefit from treatment with higher
      or lower dosages. The aim of the study was to verify the efficacy of a rationale
      for individualized immune globulin utilization and to elucidate the effects of
      care on patient outcome. METHODS: Single centre interventional study on 108
      patients with Primary Antibody Deficiencies. The objective was to determine for
      each patient the best interval between immune globulins administration in order
      to: * Keep IgG trough levels >500 mg/dL, * Minimize of major infections
      (pneumonias and infections requiring hospitalization), * Minimize of adverse
      events (AE). RESULTS: Ninthly eight per cent of patients achieved the objective
      of the study. Patients who had low switched memory B cells and low IgA serum
      levels and/or are affected by bronchiectasis and/or enteropathy and/or continued
      to experience adverse events despite pre-medications, achieved the study
      objective by shortening the administration intervals to 2-weeks or to 1-week
      without the need to increase the monthly cumulative immunoglobulin dosage and its
      relative cost. The adverse events were reduced by administrating low Ig dosages
      in a single setting. Patients without risk factors achieved the study objective
      with immune globulin replacement administered with the widely used interval of 3
      or 4 weeks. CONCLUSIONS: The exact timing and optimal immunoglobulin prophylaxis
      regimen might be tailored according to clinical and immunological markers.

PMID- 25047155
TI  - Recurrent thyroid cancers have more peritumoural lymphatic vasculature than
      nonrecurrent thyroid cancers.
AB  - BACKGROUND: The goal of the study was to evaluate angiogenesis and
      lymphangiogenesis in differentiated thyroid cancer and recurrences. METHODS:
      Twenty-seven patients with recurrent differentiated thyroid cancer (20 papillary
      and seven follicular thyroid carcinomas) and 24 nonrecurrent thyroid cancers were
      included in this study. Additionally, 24 thyroid adenomas were included as benign
      controls. All thyroid cancer recurrences were operatively managed, and local
      recurrences in cervical lymph nodes or cervical soft tissue were histologically
      confirmed. Altogether, a total of 108 samples were evaluated using CD31 and D2-40
      immunohistochemical staining and microscopy. RESULTS: As measured in primary
      tumours, the median density of CD31-positive vascular structures was 327 vessels
      (v)/mm(2) for recurrent cancers, 362 v/mm(2) for nonrecurrent cancers and 484
      v/mm(2) for thyroid adenomas (P = 0.017). Among the subgroups, the lowest median
      vascular density of 316 v/mm(2) was found in recurrent papillary cancers and the
      highest vascular density of 604 v/mm(2) was observed in nonrecurrent follicular
      cancers (P = 0.018). The median density of D2-40-positive peritumoural lymphatic
      vessels was 101/mm(2) in recurrent cancers, 56.1/mm(2) in nonrecurrent cancers
      and 53.9/mm(2) for adenomas (P = 0.015). In the subgroups, peritumoural lymphatic
      vascular density was 102 v/mm(2) in recurrent papillary cancers and 56.0 v/mm(2)
      in nonrecurrent papillary cancers (P = 0.044). CONCLUSIONS: Recurrent thyroid
      cancers expressed less intratumoural microvessels than thyroid adenomas. A high
      density of peritumoural lymphatic vessels was found in recurrent papillary
      cancers. High blood vessel density may be a marker for less aggressive tumours,
      while high peritumoural lymphatic vasculature is a marker for more aggressive and
      recurrence-prone tumours.

PMID- 25047156
TI  - Health in All Urban Policy: city services through the prism of health.
AB  - In April, 2014, the City of Richmond, California, became one of the first and
      only municipalities in the USA to adopt a Health in All Policies (HiAP) ordinance
      and strategy. HiAP is increasingly recognized as an important method for ensuring
      policy making outside the health sector addresses the determinants of health and
      social equity. A central challenge facing HiAP is how to integrate community
      knowledge and health equity considerations into the agendas of policymakers who
      have not previously considered health as their responsibility or view the value
      of such an approach. In Richmond, the HiAP strategy has an explicit focus on
      equity and guides city services from budgeting to built and social environment
      programs. We describe the evolution of Richmond's HiAP strategy and its content.
      We highlight how this urban HiAP was the result of the coproduction of science
      policy. Coproduction includes participatory processes where different public
      stakeholders, scientific experts, and government sector leaders come together to
      jointly generate policy goals, health equity metrics, and policy drafting and
      implementation strategies. We conclude with some insights for how city
      governments might consider HiAP as an approach to achieve "targeted
      universalism," or the idea that general population health goals can be achieved
      by targeting actions and improvements for specific vulnerable groups and places. 

PMID- 25047157
TI  - Food insecurity, neighborhood food access, and food assistance in Philadelphia.
AB  - An estimated 17.6 million American households were food insecure in 2012, meaning
      they were unable to obtain enough food for an active and healthy life. Programs
      to augment local access to healthy foods are increasingly widespread, with
      unclear effects on food security. At the same time, the US government has
      recently enacted major cuts to federal food assistance programs. In this study,
      we examined the association between food insecurity (skipping or reducing meal
      size because of budget), neighborhood food access (self-reported access to fruits
      and vegetables and quality of grocery stores), and receipt of food assistance
      using the 2008, 2010, and 2012 waves of the Southeastern Pennsylvania Household
      Health Survey. Of 11,599 respondents, 16.7% reported food insecurity; 79.4% of
      the food insecure found it easy or very easy to find fruits and vegetables, and
      60.6% reported excellent or good quality neighborhood grocery stores. In our
      regression models adjusting for individual- and neighborhood-level covariates,
      compared to those who reported very difficult access to fruits and vegetables,
      those who reported difficult, easy or very easy access were less likely to report
      food insecurity (OR 0.62: 95% CI 0.43-0.90, 0.33: 95% CI 0.23-0.47, and 0.28: 95%
      CI 0.20-0.40). Compared to those who reported poor stores, those who reported
      fair, good, and excellent quality stores were also less likely to report food
      insecurity (OR 0.81: 95% CI 0.60-1.08, 0.58: 95% CI 0.43-0.78, and 0.43: 95% CI
      0.31-0.59). Compared to individuals not receiving food assistance, those
      receiving Supplemental Nutrition Assistance Program (SNAP) benefits were
      significantly more likely to be food insecure (OR 1.36: 95% CI 1.11-1.67), while
      those receiving benefits from the Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC) (OR 1.17: 95% CI 0.77-1.78) and those
      receiving both SNAP and WIC (OR 0.84: 95% CI 0.61-1.17) did not have
      significantly different odds of food insecurity. In conclusion, better
      neighborhood food access is associated with lower risk of food insecurity.
      However, most food insecure individuals reported good access. Improving diet in
      communities with high rates of food insecurity likely requires not only improved
      access but also greater affordability.

PMID- 25047158
TI  - [Homozygous and compound heterozygous RYR1 mutations. New findings on prevalence
      and penetrance of malignant hyperthermia].
AB  - BACKGROUND: Malignant hyperthermia (MH) is a life-threatening, acute
      pharmacogenetic disorder mostly due to heterozygous mutations in the ryanodin
      receptor 1 (RYR1) gene. Diagnosis is generally confirmed by the in vitro
      contracture test (IVCT). In this study the genotype-phenotype correlation was
      analyzed and the presumed prevalence of MH is discussed. PATIENTS AND METHODS:
      After the diagnosis of MH susceptibility by the IVCT DNA samples of 44 patients
      were analyzed for mutations in the RYR1 gene using the polymerase chain reaction
      and sequencing. For genotype-phenotype correlation, the mutation analysis data
      were compared with the IVCT data. RESULTS: Out of the 44 patients tested 13 were
      identified with a heterozygous mutation, 1 patient with a homozygous mutation
      (c.1840C>T) and 1 patient with compound heterozygous mutations (c.1840C>T and
      c.6487C>T). The two patients with two mutated alleles showed a stronger response
      in the IVCT compared to those with only one mutated allele. Patients with one
      RYR1 mutation displayed significantly higher contractures in the IVCT than
      patients without RYR1 mutations. CONCLUSION: In the two patients described the
      presence of two mutated RYR1 alleles seemed to have an additive effect on the
      functional restriction of the (RYR1 receptor and to lead to a stronger response
      both in the IVCT and with regard to clinical signs. The patients with no detected
      RYR1 mutations possibly have a RYR1 mutation with smaller effects outside the hot
      spot regions tested and/or false positive IVCT results. The data from a small
      patient group indicate a substantially higher prevalence of MH with a
      correspondingly lower penetrance in the German population than previously
      assumed.

PMID- 25047159
TI  - [Cardiac arrest in spectators in German football stadiums. Precautionary
      measures, frequency and short-term outcome].
AB  - BACKGROUND: Provision of medical care is an important element of safety
      precautions for visitors of sports arenas. The organizational requirements are
      especially high if cardiac arrest occurs; how this scenario is managed may thus
      serve as the ultimate indicator of the quality of stadium medical care. The
      objectives of this study were to analyze the structures and the resources
      available for the medical care of spectators in German professional soccer
      stadiums and to identify the frequency and the primary resuscitation success of
      cardiac arrest. MATERIAL AND METHODS: In 2011 a questionnaire-based survey was
      performed among the clubs of the first and second German soccer leagues regarding
      medical care of spectators during the seasons 2008/2009 and 2009/2010. The focus
      was on the qualifications of emergency teams, the equipment and the incidence of
      cardiac arrest. RESULTS: A total of 15 stadiums were included (38%) in the
      survey. The mean number of physicians and emergency medical technicians on site
      was 0.6/10,000 seats and 16/10,000 seats, respectively. Of the latter, a mean of
      82% (minimum 20% and maximum 100%) had received training with automatic external
      defibrillators. In 87% of the stadiums regular advanced life support training
      (ALS) was required. The mean number of defibrillators per stadium was 2.8/10,000
      seats (minimum 1.3 and maximum 3.8) including 1.7 automatic defibrillators
      (minimum 0.4 and maximum 2.8). For patient transport, a mean of 0.65 ALS
      ambulance vehicles per 10,000 seats (minimum 0.14 and maximum 1.46) were
      available on site. In all stadiums staff members were connected via mobile radio
      communication with the stadium medical control room. A total of 52 cardiac
      arrests (=0.25/100,000 spectators) were recorded of which 96% of the patients
      were transported to hospitals with spontaneous circulation. CONCLUSIONS: Cardiac
      arrests are not a rare occurrence in German soccer stadiums. The participating
      stadiums are overall well prepared for such incidents in terms of organization,
      staff and technology and due to short response times, the resuscitation success
      by far surpasses that of the standard emergency medical services. These findings
      may in addition serve as a motivational example to start resuscitation early in
      public information campaigns.

PMID- 25047160
TI  - Detection rate of fluorine-18-fluorodeoxyglucose positron emission tomography in
      patients with marginal zone lymphoma of MALT type: a meta-analysis.
AB  - The aim of this article is to meta-analyse published data about the detection
      rate (DR) of fluorine-18-fluorodeoxyglucose ((18) F-FDG) positron emission
      tomography (PET) and PET/computed tomography (CT) in the evaluation of patients
      with marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). A
      comprehensive literature search of studies published through February 2014 was
      performed. Pooled DR of (18) F-FDG PET or PET/CT including 95% confidence
      intervals (95% CI) was calculated on a per-patient-based analysis. Twenty studies
      including 376 patients with MALT lymphoma were selected. The pooled DR of (18) F
      FDG PET or PET/CT was 71% (95% CI: 61-80%). A significant difference between the
      DR of PET/CT (69%; 95% CI: 61-80%) and that of PET alone (73%; 95% CI: 60-84%)
      was not demonstrated. A better DR of (18) F-FDG PET or PET/CT in bronchial (94%;
      95% CI: 85-99%) and head-and-neck (90%; 95% CI: 78-98%) MALT lymphomas compared
      with gastric (62%; 95% CI: 46-77%) and ocular (49%; 95% CI: 36-63%) MALT
      lymphomas was found. This meta-analysis demonstrates that MALT lymphoma is an
      (18) F-FDG-avid tumour in most of the cases, suggesting a potential clinical role
      of (18) F-FDG PET or PET/CT in the initial evaluation of these patients. In
      particular, the DR of (18) F-FDG PET or PET/CT is related to the primary site of
      the MALT lymphoma.

PMID- 25047161
TI  - Complications after arthroscopic knee surgery.
AB  - PURPOSE: To examine the complications of arthroscopic knee surgeries conducted in
      the Sports Medicine and Knee Center of our hospital. SUBJECTS AND METHODS: In
      this prospective study, a total of 2,623 patients (1,396 men and 1,227 women) who
      underwent arthroscopic knee surgeries in our center between January 2006 and
      March 2013 (7 years and 3 months) were studied. The ages at surgery ranged 7-96
      years (mean 33.5 years). Arthroscopy was conducted because of sports injuries in
      1,653 patients (63.0 %). The main diagnoses included meniscal injury in 920
      patients, discoid meniscus in 64 patients, anterior cruciate ligament injury in
      580 knees, posterior cruciate ligament injury in 30 knees, loose body in 61
      knees, and intraarticular fracture in 33 knees. Arthroscopic procedures included
      meniscectomy in 987 knees, meniscal suture repair in 262 knees, and anterior
      cruciate ligament reconstruction in 508 knees. Intraoperative and postoperative
      complications in these cases were investigated. RESULTS: The rate of complication
      was 7 in 2,623 cases (0.27 %). Intraoperative complications comprised three cases
      of intraarticular instrument breakage and one case of meniscal injury.
      Postoperative complications consisted of two cases of septic arthritis and one
      case of superficial infection, and reoperation was necessary in the two cases of
      septic arthritis. There were no neural, vascular and ligament injuries during
      surgery, and no complex regional pain syndrome, symptomatic deep vein thrombosis,
      and pulmonary embolism were observed. CONCLUSION: Arthroscopic knee surgeries are
      considered to be minimally invasive, and are conducted relatively safe with low
      complication rates. In this series, however, seven cases of complications
      occurred, including two cases (0.08 %) of septic arthritis. Furthermore,
      symptomatic thromboembolism has been reported to occur also in arthroscopic
      surgery. The risk of severe complications has to be acknowledged.

PMID- 25047162
TI  - Suspensory fixation versus novel transverse crosspin for femoral fixation in
      anterior cruciate ligament reconstruction.
AB  - BACKGROUND AND AIM: There is still no gold standard technique for graft fixation
      during anterior cruciate ligament reconstruction. We compared the functional
      outcomes of patients receiving either ToggleLoc with ZipLoop technology or
      Translig transverse crosspin device for femoral graft fixation. MATERIALS AND
      METHODS: A total of 118 patients were randomly allocated into two groups to
      receive either Translig((r)) transverse crosspin (Translig group 1: n = 51, mean
      age 28.34 +/- 7.83 years, age 18-40 years) or ToggleLoc with ZipLoop technology
      (ToggleLoc group: n = 67, mean age 26.85 +/- 8.76, age 16-41 years) for femoral
      graft fixation. Early and 1-year assessment was made with Lysholm knee scale,
      International Knee Documentation Committee Scoring, Tegner Activity Level Scale,
      KT-1000 arthrometer and pivot shift test. RESULTS: Preoperative vs. postoperative
      functional parameters showed significant improvement in both groups. Two groups
      were similar in terms of Lysholm knee scale, IKDC and Tegner activity scores (p >
      0.05). The KT-1000 arthrometer revealed slightly less anterior sliding in
      Translig group than that in ToggleLoc group (p > 0.05). ToggleLoc technique
      allowed a radiographically more horizontal placement of the graft than Translig
      technique. CONCLUSION: Two distinct techniques used in this study are likely to
      be suitable for femoral graft fixation during anterior cruciate ligament
      reconstruction with the femoral tunnel being created via anteromedial approach.

PMID- 25047163
TI  - Functional limitations as potential mediators of the effects of self-reported
      vision status on fall risk of older adults.
AB  - OBJECTIVE: To test whether limitations in mobility and large-muscle functioning
      mediate self-reported vision status to increase fall risk among respondents age
      65 and above. METHOD: This study used two waves from the Health and Retirement
      Study. We conducted binary logistic and negative binomial regression analyses to
      test indirect paths leading from self-reported vision status to falls, via
      indices of mobility and large-muscle functioning. RESULTS: Limited evidence was
      found for a mediating effect among women; however, large-muscle groups were
      implicated as partially mediating risk factors for falls among men with fair self
      reported vision status. DISCUSSION: Implications of these findings are discussed
      including the need for prioritizing improved muscle strength of older men and
      women with poor vision as a preventive measure against falls.

PMID- 25047164
TI  - Network meta-analysis of multiple outcome measures accounting for borrowing of
      information across outcomes.
AB  - BACKGROUND: Network meta-analysis (NMA) enables simultaneous comparison of
      multiple treatments while preserving randomisation. When summarising evidence to
      inform an economic evaluation, it is important that the analysis accurately
      reflects the dependency structure within the data, as correlations between
      outcomes may have implication for estimating the net benefit associated with
      treatment. A multivariate NMA offers a framework for evaluating multiple
      treatments across multiple outcome measures while accounting for the correlation
      structure between outcomes. METHODS: The standard NMA model is extended to
      multiple outcome settings in two stages. In the first stage, information is
      borrowed across outcomes as well across studies through modelling the within
      study and between-study correlation structure. In the second stage, we make use
      of the additional assumption that intervention effects are exchangeable between
      outcomes to predict effect estimates for all outcomes, including effect estimates
      on outcomes where evidence is either sparse or the treatment had not been
      considered by any one of the studies included in the analysis. We apply the
      methods to binary outcome data from a systematic review evaluating the
      effectiveness of nine home safety interventions on uptake of three poisoning
      prevention practices (safe storage of medicines, safe storage of other household
      products, and possession of poison centre control telephone number) in households
      with children. Analyses are conducted in WinBUGS using Markov Chain Monte Carlo
      (MCMC) simulations. RESULTS: Univariate and the first stage multivariate models
      produced broadly similar point estimates of intervention effects but the
      uncertainty around the multivariate estimates varied depending on the prior
      distribution specified for the between-study covariance structure. The second
      stage multivariate analyses produced more precise effect estimates while enabling
      intervention effects to be predicted for all outcomes, including intervention
      effects on outcomes not directly considered by the studies included in the
      analysis. CONCLUSIONS: Accounting for the dependency between outcomes in a
      multivariate meta-analysis may or may not improve the precision of effect
      estimates from a network meta-analysis compared to analysing each outcome
      separately.

PMID- 25047166
TI  - Sperm concentration, hyaluronic acid-binding capacity, aneuploidy and persistent
      histones in testicular cancer.
AB  - STUDY QUESTION: Are the quantitative and qualitative characteristics of semen
      samples of patients with testicular cancer (TC), prior to anticancer therapy,
      different from infertile oligozoospermic (IO) and normozoospermic (NZ) age
      matched men? SUMMARY ANSWER: Sperm concentration in TC patients was significantly
      decreased with no difference in estimated numerical chromosome aberrations and
      nuclear decondensation compared with NZ men, while the infertile, oligozoospermic
      men had significantly poorer sperm qualitative characteristics versus the TC
      group overall and oligozoospermic patients with TC. WHAT IS KNOWN ALREADY:
      Spermatogenesis is altered in TC patients at the time of diagnosis. However, the
      mechanism responsible for the decreased semen quantity in patients with TC is not
      well understood. Anticancer treatment may have gonadotoxic side effects and post
      treatment fertility cannot be predicted. Before commencing anticancer treatment,
      cryopreservation may be suggested to preserve fertility but there are no data
      regarding the risk of genetic aberrations in these sperms. STUDY DESIGN, SIZE,
      DURATION: This is a cross-sectional study examining semen from 28 patients with
      TC, 20 IO and 20 NZ age-matched men attending the Andrology Center and the Sperm
      Cryopreservation Laboratory of the Medical and Health Science Center, University
      of Debrecen. Semen samples from patients with TC were collected after
      orchidectomy, but prior to anticancer treatment. Semen samples from TC patients
      recruited over a period of 4 years were studied. Based on their sperm
      concentration, TC patients were subgrouped into an oligozoospermic TC (TCO) and a
      normozoospermic TC group. For statistical analysis, the normal group (NZ + IO)
      comprised non-tumorous NZ and IO men. PARTICIPANTS/MATERIALS/SETTING, METHOD: The
      ejaculates were assessed as per World Health Organization guidelines. Hyaluronic
      acid (HA)-binding capacity was the functional test. To determine the numerical
      chromosome aberrations, we used multi-color fluorescence in situ hybridization.
      Aniline blue (AB) staining was performed as a nuclear decondensation marker test.
      MAIN RESULTS AND THE ROLE OF CHANCE: The results did not reveal any significant
      difference in disomy of sex chromosomes and chromosome 17, diploidy and estimated
      numerical chromosome aberrations and AB staining results upon comparing the NZ
      and TC groups, although the sperm concentration (P < 0.001) and HA-binding
      capacity (P < 0.001) were lower in the TC group. Estimated numerical chromosome
      aberrations (P < 0.001), AB staining (P < 0.001) and HA-binding capacity (P =
      0.019) were lower in the infertile, oligozoospermic group when compared with the
      patients with TC. The TCO group had significantly better results in every
      examined parameter than the infertile, oligozoospermic group. In the non-tumorous
      control group (NZ + IO), a significant (P < 0.001) correlation (Spearman's rho =
      r) was found between sperm concentration and aneuploidy rate (r = -0.642), AB
      staining (r = -0.876) and HA binding (r = 0.842); the HA-binding capacity was
      related to the aneuploidy rate (r = -0.678) and the AB staining (r = -0.811); and
      there was significant correlation between aneuploidy and AB staining (r = 0.559).
      In the TC group, apart from the negative correlation between sperm concentration
      and estimated chromosomal aberrations (r = -0.642), no other correlations were
      observed. LIMITATIONS, REASONS FOR CAUTION: Data on confounders influencing sperm
      characteristics, such as smoking, occupational or environmental hazards,
      alcoholism, co-morbidities and other andrological conditions, were not collected.
      WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to demonstrate that
      sperm qualitative characteristics in anticancer therapy naive oligozoospermic TC
      patients differ significantly from those in IO men and do not differ from those
      in NZ men. Our results need to be validated in similar groups of men and in other
      patient groups with cancer where cryopreservation is advisable. STUDY
      FUNDING/COMPETING INTERESTS: This research was supported by the European Union
      and the State of Hungary, co-financed by the European Social Fund in the
      framework of TAMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. The
      authors have no conflict of interest to declare.

PMID- 25047165
TI  - Transient receptor potential channels contribute to pathological structural and
      functional remodeling after myocardial infarction.
AB  - RATIONALE: The cellular and molecular basis for post-myocardial infarction (MI)
      structural and functional remodeling is not well understood. OBJECTIVE: Our aim
      was to determine if Ca2+ influx through transient receptor potential canonical
      (TRPC) channels contributes to post-MI structural and functional remodeling.
      METHODS AND RESULTS: TRPC1/3/4/6 channel mRNA increased after MI in mice and was
      associated with TRPC-mediated Ca2+ entry. Cardiac myocyte-specific expression of
      a dominant-negative (loss-of-function) TRPC4 channel increased basal myocyte
      contractility and reduced hypertrophy and cardiac structural and functional
      remodeling after MI while increasing survival in mice. We used adenovirus
      mediated expression of TRPC3/4/6 channels in cultured adult feline myocytes to
      define mechanistic aspects of these TRPC-related effects. TRPC3/4/6
      overexpression in adult feline myocytes induced calcineurin (Cn)-nuclear factor
      of activated T-cells (NFAT)-mediated hypertrophic signaling, which was reliant on
      caveolae targeting of TRPCs. TRPC3/4/6 expression in adult feline myocytes
      increased rested state contractions and increased spontaneous sarcoplasmic
      reticulum Ca2+ sparks mediated by enhanced phosphorylation of the ryanodine
      receptor. TRPC3/4/6 expression was associated with reduced contractility and
      response to catecholamines during steady-state pacing, likely because of enhanced
      sarcoplasmic reticulum Ca2+ leak. CONCLUSIONS: Ca2+ influx through TRPC channels
      expressed after MI activates pathological cardiac hypertrophy and reduces
      contractility reserve. Blocking post-MI TRPC activity improved post-MI cardiac
      structure and function.

PMID- 25047169
TI  - Long-term results of electrical stimulation of the lower esophageal sphincter for
      treatment of proximal GERD.
AB  - INTRODUCTION: Electrical stimulation of the lower esophageal sphincter (LES) in
      gastroesophageal reflux disease (GERD) patients, using EndoStim((r)) LES
      stimulation system (EndoStim BV, the Hague, Netherlands), enhances LES pressure,
      decrease distal esophageal acid exposure, improves symptoms, and eliminates the
      need in many patients for daily GERD medications. AIM: To evaluate, in a post hoc
      analysis, the effect of LES stimulation on proximal esophageal acid exposure in a
      subgroup of patients with abnormal proximal esophageal acid exposure. METHODS:
      Nineteen patients (median age 54 years; IQR 47-64; men-10) with GERD partially
      responsive to proton pump inhibitors (PPI), hiatal hernia <= 3 cm, esophagitis <=
      LA grade C underwent laparoscopic implantation of the LES stimulator. LES
      stimulation at 20 Hz, 215 MUs, 5-8 m Amp sessions was delivered in 6-12, 30 min
      sessions each day. Esophageal pH at baseline and after 12-months of LES
      stimulation was measured 5 and 23 cm above the manometric upper border of LES.
      RESULTS: Total, upright and supine values of median (IQR) proximal esophageal pH
      at baseline were 0.4 (0.1-1.4), 0.6 (0.2-2.3), and 0 (0.0-0.2) %, respectively,
      and at 12 months on LES-EST were 0 (0-0) % (p = 0.001 total and upright; p =
      0.043 supine comparisons). 24-hour distal esophageal acid exposure improved from
      10.2 (7.6-11.7) to 3.4 (1.6-7.0) % (p = 0.001). Seven (37%) patients had abnormal
      (>1.1%) 24-hour proximal acid exposure at baseline; all normalized at 12 months
      (p = 0.008). In these 7 patients, total, upright, and supine median proximal acid
      exposure values at baseline were 1.7 (1.3-4.1), 2.9 (1.9-3.7), and 0.3 (0-4.9) %,
      respectively, and after 12 months of LES-EST were 0 (0-0.0), 0 (0-0.1), and 0 (0
      0) % (p = 0.018 total and upright; p = 0.043 supine comparisons). Distal
      esophageal pH for this group improved from 9.3 (7.8-17.2) at baseline to 3.2 (1.1
      3.7) % at 12-months (p = 0.043). There were no GI side effects such as dysphagia,
      gas-bloat or diarrhea or device or procedure related serious adverse events with
      LES-EST. There was also a significant improvement in their GERD-HRQL scores.
      CONCLUSION: LES-EST is associated with normalization of proximal esophageal pH in
      patients with GERD and may be useful in treating those with proximal GERD. The
      LES-EST is safe without typical side effects associated with traditional
      antireflux surgery.

PMID- 25047170
TI  - Measurement of gastric emptying in diabetes.
AB  - There has been a substantial evolution of concepts related to disordered gastric
      emptying in diabetes. While the traditional focus has hitherto related to the
      pathophysiology and management of upper gastrointestinal symptoms associated with
      gastroparesis, it is now apparent that the rate of gastric emptying is central to
      the regulation of postprandial glycemia. This recognition has stimulated the
      development of dietary and pharmacologic approaches to optimize glycemic control,
      at least in part, by slowing gastric emptying. With the increased clinical
      interest in this area, it has proved necessary to expand the traditional
      indications for gastric emptying studies, and consider the relative strengths and
      limitations of available techniques. Scintigraphy remains the 'gold standard' for
      the measurement of gastric emptying, however, there is a lack of standardization
      of the technique, and the optimal test meal for the evaluation of
      gastrointestinal symptoms may be discordant from that which is optimal to assess
      impaired glycemic control. The stable isotope breath test provides an alternative
      to scintigraphy and can be performed in an office-based setting. The effect of
      glucagon-like peptide-1 (GLP-1) and its agonists to reduce postprandial glycemia
      is dependent on the baseline rate of gastric emptying, as well as the magnitude
      of slowing. Because the effect of exogenous GLP-1 to slow gastric emptying is
      subject to tachyphylaxis with sustained receptor exposure, 'short acting' or
      'prandial' GLP-1 agonists primarily target postprandial glycemia through slowing
      of gastric emptying, while 'long acting' or 'non-prandial' agents lower fasting
      glucose primarily through insulinotropic and glucagonostatic mechanisms.
      Accordingly, the indications for the therapeutic use of these different agents
      are likely to vary according to baseline gastric emptying rate and glycemic
      profiles. 

PMID- 25047167
TI  - Effect of procysteine on aging-associated changes in hepatic GSH and SMase:
      evidence for transcriptional regulation of smpd3.
AB  - In hepatocytes, aging-associated decline in GSH has been linked to activation of
      neutral SMase (nSMase), accumulation of bioactive ceramide, and inflammation. In
      this study, we seek to test whether dietary supplementation with the cysteine
      precursor, L-2-oxothiazolidine-4-carboxylic acid (OTC), would correct the aging
      associated differences in hepatic GSH, nSMase, and ceramide. Young and aged mice
      were placed on a diet that either lacked sulfur-containing amino acids (SAAs) or
      had 0.5% OTC for 4 weeks. Mice fed standard chow were used as an additional
      control. SAA-deficient mice exhibited significant aging-associated differences in
      hepatic GSH, GSH/GSSG, ceramide, and nSMase. C24:1 ceramide, the major ceramide
      species in liver, was affected the most by aging, followed by the less abundant
      C16:0 ceramide. OTC supplementation eliminated the aging-associated differences
      in hepatic GSH and GSH/GSSG ratio. Surprisingly, however, instead of decreasing,
      the nSMase activity and ceramide increased in the OTC-fed mice irrespective of
      their age. These effects were due to elevated nSMase-2 mRNA and protein and
      appeared to be direct. Similar increases were seen in HepG2 cells following
      treatment with OTC. The OTC-fed aged mice also exhibited hepatic steatosis and
      triacylglyceride accumulation. These results suggest that OTC is a potent
      stimulant of nSMase-2 expression and that there may be unanticipated
      complications of OTC supplementation. 

PMID- 25047171
TI  - Job stress, burnout, and job satisfaction in sleep apnea patients.
AB  - OBJECTIVE: To assess job stress, burnout, and job satisfaction in patients with
      obstructive sleep apnea syndrome (OSAS). METHODS: A total of 182 patients with
      OSAS and 71 healthy individuals completed the Job Content Questionnaire, the
      Maslach Burnout Inventory - General Survey, the Index of Job Satisfaction, the
      Epworth Sleepiness Scale, and the Pittsburgh Sleep Quality Index. All
      participants were assessed with full-night polysomnography. RESULTS: Survey
      scores of patients diagnosed with OSAS only differed from those of the control
      group in the emotional exhaustion dimension (P = 0.015). According to a
      multivariate analysis, the apnea-hypopnea index (AHI) was only correlated with
      perceived support at work (beta coefficient = 0.142; P = 0.048). Associations
      were found between subjective sleep quality, perceived support from coworkers,
      and supervisors (beta = 0.157; P = 0.025), psychological demands (beta = 0.226; P
      = 0.001), emotional exhaustion (beta = 0,405; P = 0.000), and cynicism (beta =
      0.224; P = 0.002). The study also revealed associations between excessive daytime
      sleepiness and the burnout dimensions emotional exhaustion (beta = 0.232; P =
      0.000) and cynicism (beta = 0.139; P = 0.048). CONCLUSION: Objective parameters
      of OSAS such as the AHI seem to have limited influence on the psychosocial
      aspects of the occupational life of patients with OSAS. There is evidence of
      significant associations between the subjective symptoms of the disease, such as
      daytime sleepiness, subjective sleep quality, job stress, and burnout.

PMID- 25047172
TI  - Ethnic differences in self-reported sleep duration in The Netherlands--the HELIUS
      study.
AB  - BACKGROUND: We investigated ethnic differences in sleep duration, and the
      contribution of socio-economic status (SES) to the observed differences in
      Amsterdam, The Netherlands. METHODS: 6959 participants (aged 18-71 years) from
      the multi-ethnic HELIUS cohort were studied. Outcome variables were short sleep
      (<7 h/night) and long sleep (>=9 h/night). Comparisons among groups were made
      using Prevalence Ratios (PRs). RESULTS: Ethnic minority groups were more likely
      than ethnic-Dutch to report short sleep, with prevalence ranging from 15.1% to
      49.7% in men and 16.3% to 41.4% in women. Among men, the age-adjusted PRs ranged
      from 2.15 (95% CI 1.72-2.69) in Turkish to 3.31 (2.75-3.99) in Ghanaians; and
      among women, from 1.62 (1.30-2.01) in Turkish to 2.52 (2.15-2.95) in African
      Surinamese, respectively. The prevalence of long sleep was significantly higher
      only in Moroccan men and all the ethnic minority women than in ethnic-Dutch women
      except for African-Surinamese. Adjustment for SES explains the ethnic difference
      in long sleep, but not for short sleep. CONCLUSION: Ethnic minority groups
      reported more short sleep than ethnic-Dutch, while there were no ethnic
      differences in long sleep. Further study is needed to investigate how this
      finding on short sleep may contribute to ethnic differences in health outcomes.

PMID- 25047173
TI  - Nut consumption and the risk of coronary artery disease: a dose-response meta
      analysis of 13 prospective studies.
AB  - INTRODUCTION: Epidemiological studies evaluating the association of nut with risk
      of coronary artery disease (CAD) have produced inconsistent results. We conducted
      a meta-analysis to summarize the evidence from prospective cohort studies
      regarding the association between nut consumption and risk of CAD. MATERIALS AND
      METHODS: Pertinent studies were identified by searching Web of Knowledge, Pubmed
      and Wan Fang Med Online up to January 2014. Random-effect model was used to
      combine the results. Dose-response relationship was assessed by restricted cubic
      spline. Publication bias was estimated using Begg' funnel plot and Egger's
      regression asymmetry test. RESULTS: Nine articles with 13 prospective studies
      involving 6,127 CAD cases and 347,477 participants were included in this meta
      analysis. Pooled results suggested that highest nut consumption amount versus
      lowest amount was significantly associated with the risk of CAD [summary relative
      risk (RR)=0.660, 95%CI=0.581-0.748, I(2)=39.6%]. Linear dose-response
      relationship was found between nut consumption and CAD risk, and the risk of CAD
      decreased by 5% for every 1 serving/week increase intake of nut. A protective
      effect for CAD was found when consumed more than 2 servings/week of nut. The RR
      of CAD was 0.96 (0.89-1.02), 0.91 (0.82-0.99), 0.85 (0.77-0.95), 0.80 (0.72
      0.89), 0.75 (0.65- 0.85) and 0.70 (0.58-0.83) for 1, 2, 3, 4, 5 and 6
      servings/week of nut consumption, respectively. CONCLUSIONS: Our analysis
      indicated that nut consumption has a protective effect on CAD.

PMID- 25047174
TI  - Case fatality of bleeding and recurrent venous thromboembolism during, initial
      therapy with direct oral anticoagulants: a systematic review.
AB  - INTRODUCTION: The frequency and case fatality of venous thromboembolism (VTE) and
      major bleeding during the initial 3 months of therapy in those treated for
      symptomatic VTE with either direct oral anticoagulants (DOACs) or vitamin K
      antagonists (VKA) are important clinically relevant outcomes. We sought to
      measure it during the initial months of anticoagulation for symptomatic VTE.
      MATERIAL AND METHODS: We searched MEDLINE, EMBASE, and CENTRAL to identify
      studies that enrolled patients with acute symptomatic VTE treated with DOACs or
      VKA and reported data on bleeding, VTE recurrence and death. Studies were
      evaluated according to a priori inclusion criteria and critically appraised using
      established internal validity criteria. Single-proportion random-effects models
      were used to pool estimates. RESULTS: Of the 2453 citations retrieved, 5 RCTs
      that enrolled 24,507 patients were included. The rate of major bleeding was 1.8
      (95% CI: 1.3-2.5) and 3.1 (95% CI: 2.4-3.9) per 100 patient-years in DOAC and VKA
      arms, respectively. The rate of VTE recurrence was 3.7 (95% CI: 2.7-4.7) and 4.1
      (95% CI: 3.0-5.4) per 100 patient-years of DOAC and VKA, respectively. The case
      fatality rate of bleeding was significantly higher in the VKA arms 10.4% (95% CI:
      6.6-15.4) compared to DOACs 6.1% (95% CI: 2.7-11.7; p value for difference=0.029)
      with no statistical difference between the case fatalities for recurrent VTE. The
      rate of death from either definite major bleeding or definite recurrent VTE was
      0.27 (95% CI: 0.16-0.40) and 0.46 (95% CI: 0.32-0.63) per 100 patient-years for
      DOACs and VKAs respectively, resulting in a number needed to treat of 875 for
      DOACs to prevent one death. CONCLUSION: DOACs are attractive alternatives to VKAs
      for initial treatment of symptomatic VTE, with lower frequency and case fatality
      for major bleeding. However, the incremental safety benefit of DOACs over VKAs is
      small, with large numbers needed to treat.

PMID- 25047175
TI  - The cost of stone surgery.

PMID- 25047176
TI  - Systematic evaluation of the prognostic impact and intratumour heterogeneity of
      clear cell renal cell carcinoma biomarkers.
AB  - BACKGROUND: Candidate biomarkers have been identified for clear cell renal cell
      carcinoma (ccRCC) patients, but most have not been validated. OBJECTIVE: To
      validate published ccRCC prognostic biomarkers in an independent patient cohort
      and to assess intratumour heterogeneity (ITH) of the most promising markers to
      guide biomarker optimisation. DESIGN, SETTING, AND PARTICIPANTS: Cancer-specific
      survival (CSS) for each of 28 identified genetic or transcriptomic biomarkers was
      assessed in 350 ccRCC patients. ITH was interrogated in a multiregion biopsy data
      set of 10 ccRCCs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biomarker
      association with CSS was analysed by univariate and multivariate analyses.
      RESULTS AND LIMITATIONS: A total of 17 of 28 biomarkers (TP53 mutations;
      amplifications of chromosomes 8q, 12, 20q11.21q13.32, and 20 and deletions of 4p,
      9p, 9p21.3p24.1, and 22q; low EDNRB and TSPAN7 expression and six gene expression
      signatures) were validated as predictors of poor CSS in univariate analysis.
      Tumour stage and the ccB expression signature were the only independent
      predictors in multivariate analysis. ITH of the ccB signature was identified in 8
      of 10 tumours. Several genetic alterations that were significant in univariate
      analysis were enriched, and chromosomal instability indices were increased in
      samples expressing the ccB signature. The study may be underpowered to validate
      low-prevalence biomarkers. CONCLUSIONS: The ccB signature was the only
      independent prognostic biomarker. Enrichment of multiple poor prognosis genetic
      alterations in ccB samples indicated that several events may be required to
      establish this aggressive phenotype, catalysed in some tumours by chromosomal
      instability. Multiregion assessment may improve the precision of this biomarker.
      PATIENT SUMMARY: We evaluated the ability of published biomarkers to predict the
      survival of patients with clear cell kidney cancer in an independent patient
      cohort. Only one molecular test adds prognostic information to routine clinical
      assessments. This marker showed good and poor prognosis results within most
      individual cancers. Future biomarkers need to consider variation within tumours
      to improve accuracy.

PMID- 25047177
TI  - Imported malaria in a non-endemic area: the experience of the university of
      Campinas hospital in the Brazilian Southeast.
AB  - BACKGROUND: Although malaria in Brazil almost exclusively occurs within the
      boundaries of the Amazon Region, some concerns are raised regarding imported
      malaria to non-endemic areas of the country, notably increased incidence of
      complications due to delayed diagnoses. However, although imported malaria in
      Brazil represents a major health problem, only a few studies have addressed this
      subject. METHODS: A retrospective case series is presented in which 263 medical
      charts were analysed to investigate the clinical and epidemiological
      characterization of malaria cases that were diagnosed and treated at Hospital &
      Clinics, State University of Campinas between 1998 and 2011. RESULTS: Amongst all
      medical charts analysed, 224 patients had a parasitological confirmed diagnosis
      of malaria. Plasmodium vivax and Plasmodium falciparum were responsible for 67%
      and 30% of the infections, respectively. The majority of patients were male (83%)
      of a productive age (median, 37 years old). Importantly, severe complications did
      not differ significantly between P. vivax (14 cases, 9%) and P. falciparum (7
      cases, 10%) infections. CONCLUSIONS: Severe malaria cases were frequent among
      imported cases in Brazil outside of the Amazon area. The findings reinforce the
      idea that P. vivax infections in Brazil are not benign, regardless the endemicity
      of the area studied. Moreover, as the hospital is located in a privileged site,
      it could be used for future studies of malaria relapses and primaquine resistance
      mechanisms. Finally, based on the volume of cases treated and the secondary
      complications, referral malaria services are needed in the non-endemic areas of
      Brazil for a rapid and efficient and treatment.

PMID- 25047178
TI  - Efficient strategies for TALEN-mediated genome editing in mammalian cell lines.
AB  - TALEN is one of the most widely used tools in the field of genome editing. It
      enables gene integration and gene inactivation in a highly efficient and specific
      fashion. Although very attractive, the apparent simplicity and high success rate
      of TALEN could be misleading for novices in the field of gene editing. Depending
      on the application, specific TALEN designs, activity assessments and screening
      strategies need to be adopted. Here we report different methods to efficiently
      perform TALEN-mediated gene integration and inactivation in different mammalian
      cell systems including induced pluripotent stem cells and delineate experimental
      examples associated with these approaches.

PMID- 25047179
TI  - Dental indicators of adaptation in the Sahara Desert during the Late Holocene.
AB  - The present paper examines dental diseases and linear enamel hypoplasia among the
      Garamantes, a Late Holocene Saharan population, and aims to draw conclusions
      about nutrition and adaptation to a hyper-arid environment. Archaeological
      evidence suggests that the Garamantian diet included animal protein and local,
      Mediterranean and Near Eastern plants. Moreoever, although the Garamantes had
      developed urban centres, the size of these was not large enough to allow for
      particularly unhygienic conditions to appear. The above archaeological findings
      were partly corroborated by the current bioarchaeological study. At an intra
      population level, the Garamantes showed limited sex differences in dental disease
      prevalence, while all dental conditions increased in frequency with age, as
      expected. At an inter-population level, the frequency of all dental conditions
      was comparable to that found among other North African groups, with the exception
      of ante-mortem tooth loss. The low frequency of most dental conditions is an
      indication that the Garamantian diet was overall balanced, while the high
      frequency of ante-mortem tooth loss may be related to factors such as oral
      hygiene, food preparation or eating mode, which cannot be controlled for
      osteologically. Finally, the low frequency of enamel hypoplasia suggests either
      that the Sahara did not inflict particular stresses on the population, or, more
      likely, that the Garamantes had developed effective mechanisms for coping with
      their natural environment. 

PMID- 25047181
TI  - Respiratory glycerol metabolism of Actinobacillus succinogenes 130Z for succinate
      production.
AB  - Actinobacillus succinogenes 130Z naturally produces among the highest levels of
      succinate from a variety of inexpensive carbon substrates. A few studies have
      demonstrated that A. succinogenes can anaerobically metabolize glycerol, a waste
      product of biodiesel manufacture and an inexpensive feedstock, to produce high
      yields of succinate. However, all these studies were performed in the presence of
      yeast extract, which largely removes the redox constraints associated with
      fermenting glycerol, a highly reduced molecule. We demonstrated that A.
      succinogenes cannot ferment glycerol in minimal medium, but that it can
      metabolize glycerol by aerobic or anaerobic respiration. These results were
      expected based on the A. succinogenes genome, which encodes respiratory enzymes,
      but no pathway for 1,3-propanediol production. We investigated A. succinogenes's
      glycerol metabolism in minimal medium in a variety of respiratory conditions by
      comparing growth, metabolite production, and in vitro activity of terminal
      oxidoreductases. Nitrate inhibited succinate production by inhibiting fumarate
      reductase expression. In contrast, growth in the presence of dimethylsulfoxide
      and in microaerobic conditions allowed high succinate yields. The highest
      succinate yield was 0.75 mol/mol glycerol (75 % of the maximum theoretical yield)
      in continuous microaerobic cultures. A. succinogenes could also grow and produce
      succinate on partially refined glycerols obtained directly from biodiesel
      manufacture. Finally, by expressing a heterologous 1,3-propanediol synthesis
      pathway in A. succinogenes, we provide the first proof of concept that A.
      succinogenes can be engineered to grow fermentatively on glycerol. 

PMID- 25047182
TI  - A new mycinosyl rosamicin derivative produced by an engineered Micromonospora
      rosaria mutant with a cytochrome P450 gene disruption introducing the D-mycinose
      biosynthetic gene.
AB  - Genetic engineering of post-polyketide synthase-tailoring genes can be used to
      generate new macrolide analogs through manipulation of the genes involved in
      their biosynthesis. Rosamicin, a 16-member macrolide antibiotic produced by
      Micromonospora rosaria IFO13697, contains a formyl group and an epoxide at C-20
      and C-12/13 positions which are formed by the cytochrome P450 enzymes RosC and
      RosD, respectively. The D-mycinose biosynthesis genes in mycinamicin II
      biosynthesis gene cluster of Micomonospora guriseorubida A11725 were introduced
      into the rosC and rosD disruption mutants of M. rosaria IFO13697. The resulting
      engineered strains, M. rosaria TPMA0054 and TPMA0069, produced mycinosyl
      rosamicin derivatives, IZIV and IZV, respectively. IZIV was identified as a novel
      mycinosyl rosamicin derivative, 23-O-mycinosyl-20-deoxo-20-dihydrorosamicin. 

PMID- 25047183
TI  - European platform for photodynamic medicine: Why?

PMID- 25047184
TI  - The history of PDT in Norway Part one: Identification of basic mechanisms of
      general PDT.
AB  - Photodynamic therapy (PDT) is now an established treatment of malignant and
      premalignant dysplasias. A number of first and second generation photosensitizers
      have been studied in Norway. The aim has been to improve PDT efficiency and
      applicability. Many critical details regarding the mechanisms of PDT were
      elucidated by researchers in Norway. In this review we focus on the most
      important findings related to these basic mechanisms, such as generation of
      singlet oxygen, estimations of its lifetime, the oxygen effect itself, the
      subcellular localization of photosensitizers with different properties, their
      photodegradation during PDT and their tumour selectivity. 

PMID- 25047185
TI  - Research and development of photodynamic therapy photosensitizers in China.

PMID- 25047186
TI  - Research and development of photodynamic therapy photosensitizers in China.
AB  - Photodynamic therapy (PDT) started in the People's Republic of China in the early
      1980s after hematoporphyrin derivative (HpD) was used in China as PDT
      photosensitizer in clinical PDT for the treatment of various cancers. Since then,
      numerous domestic photosensitizers have been synthesized and evaluated. In
      general, the research and development of PDT photosensitizers in China can be
      divided into two stages. Firstly, attention was focused on the development of
      mixed porphyrin preparations similar to HpD and Photofrin II, and the second
      stage was searching for new photosensitizers with definite structures. In the
      past 2 decades three mixed porphyrin preparations and a series of new
      photosensitizers with different structures were developed and entered into formal
      clinical trials in China. This manuscript will introduce past research and
      development activities in China and present published preclinical and clinical
      data of some promising photosensitizers. 

PMID- 25047187
TI  - Photodynamic therapy for prostate cancer: One urologist's perspective.
AB  - Photodynamic therapy (PDT) has slowly found its place in the treatment of human
      disease. Currently, photodynamic therapy is being explored as a treatment option
      for localized prostate cancer. PDT for the treatment of prostate cancer will
      require ablation of both malignant and non-malignant glandular epithelium.
      Ablation of both malignant and normal epithelium adds a new treatment dimension
      since traditionally PDT has not targeted normal epithelial tissue. PDT for
      prostate cancer as currently envisioned will present challenges in terms of in
      situ monitoring of light, drug concentration, [Formula: see text] levels and
      biologic endpoints. The introduction of vascular-targeted photosensitizers
      fundamentally alters the traditional axioms for successful PDT treatment by
      obviating the need for "selective" tumor localization. Should clinical trials
      demonstrate the utility of this approach, patients with organ-confined disease
      will benefit. 

PMID- 25047180
TI  - Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis.
AB  - Angiogenesis, the formation of new vessels, is found in Multiple Sclerosis (MS)
      demyelinating lesions following Vascular Endothelial Growth Factor (VEGF) release
      and the production of several other angiogenic molecules. The increased energy
      demand of inflammatory cuffs and damaged neural cells explains the strong
      angiogenic response in plaques and surrounding white matter. An angiogenic
      response has also been documented in an experimental model of MS, experimental
      allergic encephalomyelitis (EAE), where blood-brain barrier disruption and
      vascular remodelling appeared in a pre-symptomatic disease phase. In both MS and
      EAE, VEGF acts as a pro-inflammatory factor in the early phase but its reduced
      responsivity in the late phase can disrupt neuroregenerative attempts, since VEGF
      naturally enhances neuron resistance to injury and regulates neural progenitor
      proliferation, migration, differentiation and oligodendrocyte precursor cell
      (OPC) survival and migration to demyelinated lesions. Angiogenesis, neurogenesis
      and oligodendroglia maturation are closely intertwined in the neurovascular
      niches of the subventricular zone, one of the preferential locations of
      inflammatory lesions in MS, and in all the other temporary vascular niches where
      the mutual fostering of angiogenesis and OPC maturation occurs. Angiogenesis,
      induced either by CNS inflammation or by hypoxic stimuli related to neurovascular
      uncoupling, appears to be ineffective in chronic MS due to a counterbalancing
      effect of vasoconstrictive mechanisms determined by the reduced axonal activity,
      astrocyte dysfunction, microglia secretion of free radical species and
      mitochondrial abnormalities. Thus, angiogenesis, that supplies several trophic
      factors, should be promoted in therapeutic neuroregeneration efforts to combat
      the progressive, degenerative phase of MS. 

PMID- 25047188
TI  - Photodynamic inactivation of influenza virus with fullerene C60 suspension in
      allantoic fluid.
AB  - BACKGROUND: Viruses are the most dangerous infectious contaminants of human donor
      blood and blood products. The purpose of the study was to investigate the virus
      inactivating properties of fullerene suspension regarding influenza virus in
      allantoic fluid of chicken embryos. METHODS: Influenza virus was propagated in
      chicken embryos, water suspension of C60 fullerene was added to the allantoic
      fluid. The fluid was light-irradiated at constant oxygen flow through the
      specimen, and the dynamics of virus titer was studied by virus titration in MDCK
      cells. The morphology of virions was studied by electron microscopy (EM).
      RESULTS: Dramatic drop of infectious titer (8 to 1 log10 EID50) of the virus was
      observed within 2h after start of irradiation. No change of the titers was
      observed in control specimens without fullerene, or light, or oxygen. EM study
      revealed numerous defects of virions' morphology (destruction of outer membrane)
      leading to the loss of infectious properties of the virus. CONCLUSIONS: Water
      insoluble fullerenes may be considered as a prospective way for inactivation of
      enveloped viruses in biological materials including blood products.

PMID- 25047189
TI  - Photodynamic therapy plus topical retinoids in Darier's disease.
AB  - Darier's disease is a rare, genetically determined, chronic disorder of
      keratinization. Characterized clinically by a symmetrical eruption of
      hypercheratotic papules with predilection for the seborrhoeic areas of the body.
      Many treatments have been suggested: emollients, topical retinoids,
      dermoabrasion, topical steroids and intermittent courses of oral antibiotics.
      Systemic retinoids are usually the treatment of choice. We present a small case
      series of patients treated with PDT and topical retinoids with good results. This
      therapeutic modality could represent an alternative to systemic retinoid
      treatment. 

PMID- 25047190
TI  - The application of 5-aminolevulinic acid-induced fluorescence for cystoscopic
      diagnosis and treatment of bladder carcinoma.
AB  - PURPOSE: To investigate the clinical application of 5-aminolevulinic acid (ALA)
      assisted fluorescence cystoscopy for early detection of bladder carcinoma and
      completely transurethral resection. METHOD: ALA-assisted fluorescence cystoscopy
      was performed on 51 cases of anodynia haematuria. Fluorescence cystoscopy was
      performed with a D-Light system 2-3h after intravesical instillation of 5-ALA.
      Biopsy was performed in fluorescence positive regions and/or the fluorescence
      negative regions with an abnormal gross appearance under a white light. Thirty
      two biopsies were subjected to frozen sectioning and the fluorescence
      distributions were analyzed with a confocal fluorescence microscopy and PpIX
      fluorescence contents in different tissues were quantified. Transurethral
      resection was performed in fluorescence positive regions. RESULTS: Red
      fluorescence (fluorescence positive) was found in 47 cases, among them 40
      urothelial carcinomas and seven benign lesions confirmed by pathological
      examination; fluorescence negative was found in four cases of benign lesions. The
      sensitivity of fluorescence cystoscope for the diagnosis of bladder carcinoma was
      97.1% (68/70) with a false-positive rate of 23.6% (21/89). Micro-fluorescence
      positive regions were found near the tumor or at distant region in 19 cases of
      transitional cell carcinoma with two carcinoma in situ unidentifiable with white
      light, and were confirmed of the existence of malignancy by biopsy. ALA-induced
      PpIX fluorescence was mainly distributed on the surface layer of the tissue and
      PpIX fluorescence was fairly weak in the deep tissue. Fluorescence quantization
      showed that the fluorescence intensity of the surface layer of the tissue was 5
      10 fold higher than deep tissue, which was correlated with the grade of tumor
      (G3>G1-2), but the mean fluorescence intensity in tumor tissue was significantly
      higher than that of benign lesions. CONCLUSION: ALA-assisted fluorescence
      cystoscope offers a simple photodynamic diagnosis approach for the diagnosis of
      bladder carcinoma, in particular, flat and small malignant lesions.

PMID- 25047191
TI  - Topical 5-aminolevulinic acid-mediated photodynamic therapy for oral verrucous
      hyperplasia, oral leukoplakia and oral erythroleukoplakia.
AB  - BACKGROUND: Our previous studies showed that a new topical 5-aminolevulinic acid
      mediated photodynamic therapy (ALA-PDT) protocol using a light-emitting diode
      (LED) light source is an effective and successful treatment modality for oral
      verrucous hyperplasia (OVH). In this study, we reported and compared the clinical
      outcomes of 24 OVH lesions, 97 oral leukoplakia (OL) lesions and 6 oral
      erythroleukoplakia (OEL) lesions treated with topical ALA-PDT in the National
      Taiwan University Hospital, Taipei, Taiwan from November 2001 to December 2005.
      METHODS: Twenty-four OVH lesions, 65 OL lesions and 6 OEL lesions were treated
      with topical ALA-PDT once a week and 32 OL lesions were treated with the same
      topical ALA-PDT twice a week. Their clinical outcomes between two different
      groups were compared by Chi-square test. RESULTS: All the 24 OVH lesions treated
      once a week showed complete response (CR) after 1-6 (mean, 3.5) treatments of ALA
      PDT. The 65 OL lesions treated with topical ALA-PDT once a week showed CR in 5,
      partial response (PR) in 33 and no response (NR) in 27. The 32 OL lesions treated
      with the same topical ALA-PDT twice a week demonstrated CR in 11 and PR in 21.
      The 32 OL lesions treated twice a week had a significantly better clinical
      outcome than the 65 OL lesions treated once a week (P<0.001). The six OEL lesions
      treated with topical ALA-PDT once a week showed CR in four and PR in two. The 6
      OEL lesions treated once a week had a significantly better clinical outcome than
      the 65 OL lesions treated once a week (P<0.001). CONCLUSION: We conclude that
      complete regression of OVH lesions can be achieved by less than seven treatments
      of topical ALA-PDT once a week. OL lesions treated twice a week have a
      significantly better clinical outcome than OL lesions treated once a week. In
      addition, OEL lesions treated once a week have a significantly better clinical
      outcome than OL lesions treated once a week.

PMID- 25047192
TI  - Photodynamic therapy of port wine stains-a report of 238 cases.
AB  - OBJECTIVE: Retrospective analysis of clinical effects of vascular acting
      photodynamic therapy (PDT) for the treatment of port wine stains (PWS). METHODS:
      Between September 1997 and June 2003, a total of 238 PWS cases (2-56 years old)
      were treated with Photocarcinorin-mediated PDT using a copper vapour laser. Among
      them, 20 cases were pink lesions (Type I), 44 cases red lesions (Type II), 99
      cases dark red lesions (Type III), 51 cases purple lesions (Type IV), and 24
      cases nodular or thickened lesions (Type V), respectively. Patient received a
      slow intravenous injection of Photocarcinorin (4-5mg/kg b.w.) and light was
      delivered during the drug injection at dose levels of 160-260J/cm(2) at fluence
      rates of 70-100mW/cm(2). The same procedure was repeated 2-4 times for some
      patients. All patients were followed up for 6 months to 4 years. RESULTS: Sixty
      eight cases (28.6%) showed excellent response, 76 cases (31.9%) good response, 87
      cases (36.6%) fair response and 7 cases (2.9%) poor or no response. Secondary
      scar formation was reported in three cases. Highest good to excellent response
      rates were seen in patients of 5-20 years old. PDT-induced transitional
      hyperpigmentation was reported in some patients but disappeared without the need
      of treatment within 3-6 months. CONCLUSION: Copper vapour laser PDT can
      selectively destroy PWS vessels without damage to the normal skin. If the
      technique is applied properly, it can cure superficial lesions and greatly
      improve thick lesions.

PMID- 25047193
TI  - Photodynamic therapy combined with local chemotherapy for the treatment of
      advanced esophagocardiac carcinoma.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an effective palliative treatment for
      gastrointestinal tumors. The aim of this clinical study was to evaluate the
      efficacy of PDT combined with local chemotherapy for the treatment of advanced
      esophagocardiac cancer. METHODS: A total of 140 patients with advanced
      esophagocardiac cancer were divided into two groups: 42 treated with PDT alone
      and 98 with combination of PDT and local injection of 5-fluorouracil (5-Fu). The
      light irradiation was carried out through a diffuser fiber at 24 and 48h after
      intravenous injection of a domestic photosensitizer PSD-007 (Photocarcinorin, 3
      5mg/kg b.w.) at 200-400J/cm under endoscope guidance. Local chemotherapy group
      was carried out by local injection of 5-Fu (250-500mg) prior to PDT. Treatment
      was repeated 1-4 times. Short-term and long-term follow up were evaluated.
      RESULTS: Short-term efficacy evaluation showed that the rate of significant
      remission in PDT combined with local chemotherapy group (41.8%) was significantly
      higher than that in PDT alone group (21.4%, P<0.05). Long-term follow up (up to
      36 months) showed that the mean survival time of combined treatment group was
      longer than that of PDT group (P<0.01). CONCLUSION: PDT is safe and effective for
      advanced esophagocardiac cancer. Its therapeutic effect can be further improved
      when combined with local chemotherapy.

PMID- 25047194
TI  - A cost comparison of photodynamic therapy and metallic stents in the palliation
      of oesophageal cancer.
AB  - BACKGROUND: There is currently little information on the cost effectiveness of
      photodynamic laser therapy (PDT) compared with other palliative treatments for
      oesophageal cancer. AIM: To compare the cost of oesophageal cancer palliation
      associated with PDT with those of another standard option, self-expanding
      metallic stents. METHODS: A cost comparison study using prospectively and
      retrospectively collected data was conducted. Data was collected from 25 patients
      who had received PDT between 1999 and 2003. Costs were compared with data from
      patients who received a metallic stent between 1998 and 2000. Costs were
      estimated using routine costs for the year 2002-2003. RESULTS: Patients receiving
      PDT or oesophageal stents were similar in terms of age, gender and tumour
      presentation. Patients receiving PDT had slightly shorter duration of symptoms,
      less metastatic spread but similar dysphagia scores to those in the oesophageal
      stent group. Costs of initial PDT treatment were significantly higher than those
      associated with stent placement (PDT mean costs L2068.48 versus stent mean costs
      L1086.76; cost difference L981.72 (95% CI: L844.47-1118.96)). This higher cost
      persisted throughout future re-interventions and hospital episodes. Patients
      receiving PDT survived longer however (132.5 (70.5-250 days) (medium IQR)) than
      those receiving a stent 105 (31-172.5 days), thus the mean cost per day's
      survival was equivalent between the two treatments. There was no impact of PDT on
      patients' quality of life at 6 weeks post-treatment. CONCLUSIONS: Although
      initially more expensive than metallic stents, a longer survival results in PDT
      being as cost effective as stenting in oesophageal palliation. A larger,
      randomised controlled trial is required combining both economic evaluation and
      quality of life measurement to fully establish the best palliative treatment in
      this disease.

PMID- 25047195
TI  - Photodiagnosis for frameless stereotactic biopsy of brain tumor.
AB  - Stereotactic biopsy is a minimally invasive method of reaching a pathological
      diagnosis. However, it is not always possible with this method to obtain the
      tissue samples required for an exact pathological diagnosis. The factors that can
      make histological diagnoses uncertain are the heterogeneity of tumors and/or
      brain shifts in the case of small tumors. In this study, we investigated the
      usefulness of fluorescence in determining the existence of tumor components in
      obtained tissues. Six patients underwent stereotactic biopsy. 5-Aminolevulinic
      acid (5-ALA) was administered orally prior to operation. Frameless stereotactic
      biopsies were performed. The obtained samples were irradiated with 405nm light
      and all samples showed red light excitation. Intraoperative rapid pathological
      diagnosis was made in each case by microscopic examination of frozen section
      samples. The final pathological diagnoses were of three glioblastomas, one
      astrocytoma grade 3, and two malignant lymphomas. One case was initially thought
      to be gliosis on rapid pathological diagnosis, but the final pathological
      diagnosis reached by examination of a permanent HE stained section was
      astrocytoma grade 3. Another case, finally diagnosed as malignant lymphoma, was
      initially diagnosed as infiltration of lymphocytes. The discrepancies between
      rapid and permanent pathological diagnoses might be caused by the destruction of
      cells. 5-ALA photodynamic diagnosis is not influenced by the destruction of
      tissues, simply because it does not depend on the structure of tissues.
      Stereotactic fluorescence biopsy is very useful in that it enables rapid and
      exact biopsy and obviates the necessity of waiting for an intraoperative report
      from a pathologist. 

PMID- 25047196
TI  - Balanoposthitis with epithelial dysplasia treated by photodynamic therapy.
AB  - BACKGROUND: Balanoposthitis is the inflammation of the glans and foreskin of the
      penis. Balanoposthitis is a risk factor of penis cancer. Photodynamic therapy
      using topical aminolaevulinic acid could be an alternative therapeutic approach
      in cases resistant to conventional treatment. OBJECTIVE: We present the case of
      50-year-old male with balanoposthitis associated with epithelial dysplasia
      treated by topical aminolaevulinic acid photodynamic therapy. METHODS: On
      admission, 2hours after topical application of aminolaevulinic acid we performed
      the photodynamic diagnosis estimating pathological fluorescence of the lesions.
      Then 4 hours after topical application of aminolaevulinic acid we followed
      irradiation using light in the wavelength 630nm and giving a dose 120J/cm(2).
      RESULTS: After 5 procedures of photodynamic therapy we noticed complete recovery.
      CONCLUSION: Photodynamic therapy appears to be an alternative, non-invasive, well
      tolerated method of treatment of eithelial dysplasia of the penis.

PMID- 25047198
TI  - Improving diagnostic and therapeutic aspects of nodular goitre.

PMID- 25047197
TI  - Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo
      mandibular syndrome.
AB  - Elucidating the function of highly conserved regulatory sequences is a
      significant challenge in genomics today. Certain intragenic highly conserved
      elements have been associated with regulating levels of core components of the
      spliceosome and alternative splicing of downstream genes. Here we identify
      mutations in one such element, a regulatory alternative exon of SNRPB as the
      cause of cerebro-costo-mandibular syndrome. This exon contains a premature
      termination codon that triggers nonsense-mediated mRNA decay when included in the
      transcript. These mutations cause increased inclusion of the alternative exon and
      decreased overall expression of SNRPB. We provide evidence for the functional
      importance of this conserved intragenic element in the regulation of alternative
      splicing and development, and suggest that the evolution of such a regulatory
      mechanism has contributed to the complexity of mammalian development. 

PMID- 25047199
TI  - Epidemiology of nodular goitre. Influence of iodine intake.
AB  - More than one tenth of the world population is to some degree affected by goitre
      and most of these harbour nodules. The large differences in thyroid disease
      prevalence between populations may be caused by genetic and environmental
      factors. Among the latter, iodine deficiency seems by far to be the most
      important risk factor. Thus, nodular goitre is a condition predominantly seen in
      iodine deficient areas of the world. In the present review, we evaluated in
      detail autopsy and ultrasound studies of the thyroid gland. In autopsy studies,
      large thyroid volumes and high frequencies of goitres have been reported in
      countries affected by iodine deficiency. Many cross-sectional studies using
      thyroid ultrasound investigations have been performed world-wide and reported
      high thyroid volumes and goitre prevalences, and to some extent also high
      prevalences of thyroid nodules in iodine-deficient countries. Most of these
      goitres were classified as nodular goitres. On the other hand, few studies have
      shown that abundant iodine intake may lead to development of diffuse goitres, but
      world-wide this has been a minor problem compared with development of nodular
      goitres. In the past century we have observed a trend towards smaller thyroid
      glands, and hopefully less than 10% of the world population will experience
      goitre within a few decades. 

PMID- 25047200
TI  - The impact of goitre and its treatment on the trachea, airflow, oesophagus and
      swallowing function. A systematic review.
AB  - In this systematic review, we investigated the effects of goitre and its
      treatment on the trachea and the oesophagus. A total of 6355 papers were screened
      in scientific databases, which disclosed 40 original studies (nine descriptive
      and 31 interventional). Although most studies are hampered by a number of
      methodological shortcomings, it is uncontested that goitre affects the trachea as
      well as the oesophagus in a large proportion of people. This leads to upper
      airway obstruction, swallowing dysfunction, or both, which may remain undisclosed
      unless specifically investigated for. Assessment of the tracheal dimensions
      should be done by magnetic resonance imaging or computed tomography, and
      detection of upper airway obstruction by flow volume loops, with focus on the
      inspiratory component. A clinical evaluation of the oesophageal function is
      difficult to implement and could be replaced by available and validated
      questionnaires on swallowing. Although radioiodine therapy and thyroidectomy
      relieve the negative effect of goitre on the trachea and the oesophagus, many
      issues remain unexplored. 

PMID- 25047201
TI  - Genetic and non-iodine-related factors in the aetiology of nodular goitre.
AB  - Genetic and a large number of environmental non-iodine-related factors play a
      role in the cause of nodular goitre. Most evidence for the influence of genetic
      and environmental factors in the cause of goitre is from cross-sectional,
      population-based studies. Only a few studies have included prospective data on
      risk factors for nodular goitre, although few prospective data are available on
      the effect of iodine and tobacco smoking on goitre development. Goitre is not one
      single phenotype. Many epidemiological studies do not distinguish diffuse from
      nodular goitre, as the investigated parameter is often thyroid volume or
      frequency with increased thyroid volume. Moreover, information on the presence
      and effect of gene-environment, gene-gene, and environment-environment effect
      modifications is limited. Thus, firm conclusions about the relative contributions
      and causality of the investigated risk factors should be made with caution.
      Smoking seems to be an established risk factor for nodular goitre, possibly with
      effect modification from iodine intake, as the risk associated with smoking is
      smaller or absent in areas with sufficient iodine intake. The use of oral
      contraceptives might have protective effects against goitre, and childbirth is an
      increased risk factor for goitre in areas with non-optimal iodine intake. Insulin
      resistance is a recently investigated risk factor, and the risk of goitre may be
      reversible with metformin treatment. Iodine remains the major environmental risk
      factor for nodular goitre. 

PMID- 25047202
TI  - Role of isotope scan, including positron emission tomography/computed tomography,
      in nodular goitre.
AB  - Nuclear medicine techniques were first used in clinical practice for diagnosing
      and treating thyroid diseases in the 1950s, and are still an integral part of
      thyroid nodules work-up. Thyroid imaging with iodine or iodine-analogue isotopes
      is the only examination able to prove the presence of autonomously functioning
      thyroid tissue, which excludes malignancy with a high probability. In addition, a
      thyroid scan with technetium-99m-methoxyisobutylisonitrile is able to avoid
      unnecessary surgical procedures for cytologically inconclusive thyroid nodules,
      as confirmed by meta-analysis and cost-effectiveness studies. Finally, positron
      emission tomography alone, and positron emission tomography combined with
      computed tomography scans with (18)F-fluoro-2-deoxy-d-glucose are also promising
      for diagnosing thyroid diseases, but further studies are needed before
      introducing them to clinical practice. 

PMID- 25047203
TI  - Diagnostic role of ultrasound and elastosonography in nodular goiter.
AB  - Among several ultrasound patterns, thyroid nodule hypoechogenicity, spot
      microcalcifications, and an absent halo sign are used for predicting increased
      risk of thyroid malignancy. The predictive value of ultrasound, however,
      increases at the expense of its sensitivity, and malignancy is predicted with
      high specificity only when multiple ultrasound features are simultaneously
      present. Ultrasound features are important in determining the strength of the
      indication for carrying out fine needle aspiration. To this end, a system for
      standardization of ultrasound features (Thyroid Imaging Reporting and Data
      System) aids in establishing risk of malignancy. Ultrasound elastosonography is a
      technique that assesses hardness as an indicator of malignancy risk. It has been
      carried out in selected studies of patients with thyroid nodules, and has been
      shown to have a high predictive value for malignancy, which is also maintained in
      cytologically indeterminate and non-diagnostic nodules. Although conventional
      ultrasound maintains its pivotal role in defining which nodules are candidates
      for ultrasound elastosonography characterization, the latter seems to have
      considerable potential in the diagnosis, or exclusion, of thyroid cancer. This
      especially concerns thyroid nodules with indeterminate cytology at fine-needle
      aspiration. 

PMID- 25047204
TI  - Current role and value of fine-needle aspiration in nodular goitre.
AB  - Thyroid nodules are common and, depending on the detection technique used, can
      affect 50% or greater of the population. The primary diagnostic test to assess
      the nature of these nodules is fine-needle aspiration cytology. Most thyroid
      nodules are benign and often are multiple. However, the morphology of these
      nodules may mimic neoplasms showing features such as papillary growth, micro
      follicles and even oncocytic metaplasia. Lesions with these features may be
      considered indeterminate for neoplasm or malignancy, and often require surgical
      excision to define their nature. The role of cytopathology in this area is to
      screen those definitely benign nodules, thus preventing surgery and reassuring
      both the patient and the clinician. In this review, we demonstrate many of the
      morphological manifestations of nodular goiter and stress the necessity of
      careful preparatory techniques. Although the past several years have witnessed
      the development of molecular testing to refine diagnostic cytology in the
      thyroid, it is still the role of the cytopathologist to identify those
      "indeterminant" nodules which should be tested. Thus, the cytopathologist
      contributes both an essential diagnostic and an important cost saving role which
      hopefully will continue in the future. 

PMID- 25047205
TI  - Ruling in or ruling out thyroid malignancy by molecular diagnostics of thyroid
      nodules.
AB  - Routine morphologic cytology is the basis for any kind of (integrated) molecular
      FNA diagnostics. The rule out (gene expression classifier) approach requires
      confirmation by independent studies, whereas the rule in approach (detection of
      BRAF, NRAS, HRAS, and KRAS and PAX8/PPARG- and RET/PTC rearrangements) has been
      investigated by several groups with overall reproducible results. Moreover,
      molecular screening for point mutations and rearrangements is feasible in routine
      air-dried FNA smears, offering several advantages over obtaining additional fresh
      FNA material. The current panel of somatic mutations (rule in approach) for
      indeterminate FNAs clarifies only a subgroup of indeterminate FNAs. Therefore,
      further markers are urgently needed that can reliably identify the malignant, but
      mutation negative and especially the many benign nodules, among the indeterminate
      FNAs. miRNA markers and the targeted next generation sequencing (NGS) technology
      do have the potential to identify those nodules that are mutation negative by
      current approaches. 

PMID- 25047206
TI  - Assessing health-related quality of life in patients with benign non-toxic
      goitre.
AB  - Health-related quality of life (HRQoL) assessments are increasingly used to
      evaluate treatment effects and to shape the delivery of value based care. Valid
      generic and disease specific tools are available for quantifying HRQoL in
      patients with non-toxic goitre. However, few studies have applied these validated
      instruments to assess HRQoL in patients with benign non-toxic goitre. Limited
      evidence suggests that patients with non-toxic goitre have HRQoL impairments in
      multiple HRQoL domains. While the HRQoL-impact of non-toxic goitre may be small
      relative to other severely disabling medical conditions, treatment is almost
      exclusively elected for HRQoL indications. Thus better quantification of HRQoL,
      particularly at better (or more favorable) levels where many patients score, is
      essential. Web and mobile technologies have eased the ability to deliver surveys
      to patients. Routine consideration of HRQoL provides the opportunity to monitor
      the impact of treatment on the outcomes most meaningful for patients and the
      opportunity to help shape the delivery of value based health care. 

PMID- 25047207
TI  - Influence of iodization programmes on the epidemiology of nodular goitre.
AB  - Iodine is essential for the synthesis of thyroid hormones. Iodine deficiency can
      affect human health in different ways, and is commonly referred to as iodine
      deficiency disorders (IDD). These range from defective development of the central
      nervous system during the fetal-neonatal life, to goitre in the adult. Only a few
      countries were completely iodine sufficient before 1990. Since then, a major
      effort has been made to introduce salt iodization to ensure sufficient intake of
      iodine in deficient areas. Iodine prophylaxis has been shown to exert a pivotal
      role in abating goitre and other iodine-deficiency disorders, and has also been
      shown to modulate the pattern of thyroid diseases. An increased frequency of
      thyroid autoimmunity and of hypothyroidism has been observed after introducing
      iodization programmes. Nevertheless, available evidence clearly confirms that the
      benefits of correcting iodine deficiency, consisting mainly of reducing nodular
      goitre and non-autoimmune hyperthyroidism, far outweigh the risks of iodine
      supplementation. 

PMID- 25047208
TI  - Minimally invasive compared with conventional thyroidectomy for nodular goitre.
AB  - Since minimally invasive thyroidectomy was introduced in 1997, different surgical
      approaches to the thyroid have been described: the minimal neck incision and the
      anterior chest, areolar breast or axillary access. Whereas conventional open
      thyroidectomy is suitable for any thyroid disease, minimal neck incision
      thyroidectomy or extracervical scarless neck thyroidectomy are limited to small
      volume disease. In 11 prospective randomized studies and six systematic reviews,
      minimally invasive video-assisted thyroidectomy via a central or lateral neck
      approach afforded better cosmesis in the first 3 months than conventional open
      thyroidectomy, with less postoperative pain for the first 48 h. Surgical
      morbidity did not differ in these limited studies. No head-to-head comparison is
      available for extracervical scarless neck thyroidectomy and conventional open
      thyroidectomy. Extracervical scarless neck thyroidectomy caused more
      postoperative pain and gave rise to complications not seen with minimal neck
      incision thyroidectomy or conventional open thyroidectomy. In the absence of
      evidence to the contrary, conventional open thyroidectomy continues to remain the
      gold standard for any nodular goitre.

PMID- 25047209
TI  - The advent of ultrasound-guided ablation techniques in nodular thyroid disease:
      towards a patient-tailored approach.
AB  - Surgery is the long-established therapeutic option for benign thyroid nodules,
      which steadily grow and become symptomatic. The cost of thyroid surgery, the risk
      of temporary or permanent complications, and the effect on quality of life,
      however, remain relevant concerns. Therefore, various minimally invasive
      treatments, directed towards office-based management of symptomatic nodules,
      without requiring general anaesthesia, and with negligible damage to the skin and
      cervical tissues, have been proposed during the past two decades. Today,
      ultrasound-guided percutaneous ethanol injection and thermal ablation with laser
      or radiofrequency have been thoroughly evaluated, and are accessible procedures
      in specialized centres. In clinical practice, relapsing thyroid cysts are
      effectively managed with percutaneous ethanol injection treatment, which should
      be considered therapy of choice. In solid non-functioning thyroid nodules that
      grow or become symptomatic, trained operators may safely induce, with a single
      session of laser ablation treatment or radiofrequency ablation, a 50% volume
      decrease and, in parallel, improve local symptoms. In contrast, hyperfunctioning
      nodules remain best treated with radioactive iodine, which results in a better
      control of hyperthyroidism, also in the long-term, and fewer side-effects.
      Currently, minimally invasive treatment is also investigated for achieving local
      control of small size neck recurrences of papillary thyroid carcinoma in patients
      who are poor candidates for repeat cervical lymph node dissection. This
      particular use should still be considered experimental. 

PMID- 25047210
TI  - The role of radioiodine therapy in benign nodular goitre.
AB  - For treatment of benign nodular goitre the choice usually stands between surgery
      and (131)I therapy. (131)I therapy, used for 30 years for this condition, leads
      to a goitre volume reduction of 35-50% within 1-2 years. However, this treatment
      has limited efficacy if the thyroid (131)I uptake is low or if the goitre is
      large. Recombinant human TSH (rhTSH)-stimulated (131)I therapy significantly
      improves goitre reduction, as compared with conventional (131)I therapy without
      pre-stimulation, and adverse effects are few with rhTSH doses of 0.1 mg or lower.
      RhTSH-stimulated (131)I therapy reduces the need for additional therapy due to
      insufficient goitre reduction, but the price is a higher rate of hypothyroidism.
      Another approach with rhTSH-stimulation is to reduce the administered (131)I
      activity by a factor that equals the increase in the thyroid (131)I uptake. Using
      this approach, radiation exposure is considerably reduced while the goitre
      reduction is similar to that obtained with conventional (131)I therapy.

PMID- 25047211
TI  - Comparison of dermal tumor promotion activity of cigarette smoke condensate from
      prototype (heated) cigarette and reference (combusted) cigarette in SENCAR mice.
AB  - Test cigarette (prototype "heated" cigarette) was evaluated on its dermal tumor
      promotion activity in SENCAR mice relative to conventional 3R4F cigarette.
      Mainstream cigarette smoke was generated under the modified Health Canada
      Intensive Regimen, and smoke condensate (CSCs) were collected using cold traps
      and extracted with acetone. Female mice received a topical application of 7,12
      dimehtylbenz(a)anthracene (DMBA) as the tumor initiator on the back skin during
      Week 1. Subsequently, CSC was repeatedly applied as the tumor promoter at 5
      doses, up to 30 mg tar/application, three times per week for 30 weeks. Test
      groups showed a clearly longer latency at lower doses (?15 mg), but the
      difference was less clear at higher doses (?22.5 mg), while mortalities were not
      affected throughout the study. Test groups also had consistently lower incidence
      and multiplicity of neoplasms, as well as lower incidences of non-neoplastic
      changes (e.g., inflammations and squamous epithelial hyperplasia on the site of
      application). The group without DMBA initiation did not induce any neoplasm but
      the respective Reference group showed an increase in tumorigenicity. In
      conclusion, the study demonstrated significant reduction in dermal irritancy and
      tumorigenicity of Test CSC compared to Reference CSC.

PMID- 25047212
TI  - The use of in vitro testing to refine cumulative assessment groups of pesticides:
      The example of teratogenic conazoles.
AB  - The most relevant issues in cumulative risk assessment (CRA) are the
      identification of cumulative assessment groups and the hypothesis of dose
      additivity, at relevant human exposures. In vitro methods can provide meaningful
      data to help solving those issues. Integration of in vitro studies, selected in
      vivo studies, and PBPK modeling for teratogenic conazoles confirmed that in vitro
      studies may give results in a cheaper and faster fashion. In particular, in vitro
      studies with explanted rat embryos provided support for dose-additivity for
      conazoles causing cranio-facial malformations. Although this could not be
      immediately quantitatively transferred to the in vivo situation, they provided
      indication on how to conduct targeted in vivo studies. In addition, by means of
      PBPK modeling, it was possible to estimate the dose in humans associated with a
      defined teratogenic risk and also to conclude that for cumulative risk assessment
      only exposures occurring within a short period of time (a day or less) need to be
      cumulated. Although PBPK modeling cannot be widely applied, at least in the short
      term, it should be considered if available. It is recommended to incorporate in
      vitro testing and PBPK modeling, whenever available and feasible in the process
      of risk assessment, particularly of CRA. 

PMID- 25047213
TI  - Polycyclic aromatic hydrocarbon concentrations in commercially available infant
      formulae in Nigeria: estimation of dietary intakes and risk assessment.
AB  - The concentrations and profiles of polycyclic aromatic hydrocarbons (PAHs) in
      commercially available infant formulae and follow-up formulae in Nigeria were
      determined with a view to providing information on the health risks to children
      from the consumption of these infant foods. The concentrations of PAHs were
      measured by means of gas chromatography-mass spectrometry (GC-MS) after
      extraction by ultrasonication with acetone/dichloromethane and clean-up. The
      concentrations of the Sigma16 PAHs in these infant formulae ranged from 0.102 to
      1.98 MUg kg(-1), 0.054-1.98 MUg kg(-1), 0.081-2.54 MUg kg(-1) and 0.51-0.70 MUg
      kg(-1) for infants of ages 0-6 months, 6-12 months, 1-3 years and 0-12 months
      respectively. The concentrations of benzo(a)pyrene (BaP) in all samples
      investigated were below the 1 MUg kg(-1) European Commission permissible limit
      for BaP in foods meant for infants. The estimated daily intake of PAHs based on
      the European Food Safety Authority (EFSA) suggested indicators of occurrence and
      effects of PAHs in foods were not detected (nd) to 2.67 ng BaP kg(-1) bw day(-1),
      nd-5.29 ng PAH2 kg(-1) bw day(-1), nd-11.20 ngPAH4 kg(-1) bw day(-1) and nd-34.96
      ng PAH8 kg(-1) bw day(-1). The estimated margin of exposure (MOE) values: BaP
      MOE, PAH2-MOE, PAH4-MOE and PAH8-MOE values were greater than 10,000 which
      indicates that there are no health risks from the consumption of these products
      by infants. The concentrations and dietary exposure to PAHs from these products
      were similar to values reported in the literature for European Communities.

PMID- 25047215
TI  - Nanocomposite of europium organic framework and quantum dots for highly sensitive
      chemosensing of trinitrotoluene.
AB  - Luminescent metal-organic frameworks (MOFs) are considered as next-generation
      sensor materials for small molecules and explosives. In the present work, a
      nanocomposite of luminescent europium organic framework (EuOF) and CdSe quantum
      dots (QDs) has been first time investigated for photoluminescence (PL) based
      highly sensitive detection of trinitrotoluene (TNT). The nanocomposite EuOF/QD
      has been synthesized by initiating the growth of EuOF in the presence of QDs. The
      successful synthesis of the product has been verified with the help of electron
      microscopy, X-ray diffraction analysis, and surface area measurements. Compared
      to EuOF alone, the EuOF/QD nanocomposite offers reproducible and stable
      measurements. The linear range of PL quenching based detection of TNT with
      EuOF/QD nanocomposite is 5-1000 ppb with the detection limit of 3 ppb. The
      detection of TNT with EuOF/QD is selective with respect to some other
      investigated aromatic compounds, such as phenol, o-cresol, toluene, benzene,
      nitrobenzene and nitrophenol.

PMID- 25047216
TI  - Frequency filtering to suppress background noise in fingerprint evidence:
      quantifying the fidelity of digitally enhanced fingerprint images.
AB  - Fingerprint evidence can benefit in image quality if transformed using digital
      image processing techniques. This is especially true when considering prints that
      cannot be easily lifted (such as those deposited on porous paper substrates), or
      when the mechanism of lifting does not effectively reduce background
      interferences. In these instances, frequency filtering is one type of
      mathematical transformation that can serve to increase image clarity and the
      ability to extract minutiae relevant to pairwise comparisons. To quantify the
      impact of frequency filtering on image quality, high quality and low quality
      (noisy) prints were collected. The high quality prints served as exemplars that
      were compared to the low quality prints both pre- and post-filtering. The
      resulting pairwise match scores indicate that: (1) frequency filtering has a low
      probability of creating false positive associations, (2) 90% of the post-filtered
      images result in a normalized gain in match score, (3) frequency filtering
      doubled the probability of obtaining match scores greater than 30% (for the
      automated algorithm employed in this study), and (4) filtering can double the
      probability of obtaining 10 or more matching minutiae when comparing same source
      prints. Overall, the research indicates a reasonable and quantifiable payoff in
      increased clarity, matching minutiae and pairwise similarity for post-filtered
      images when compared to known-match exemplars. 

PMID- 25047214
TI  - Retrospective study of biopsied head and neck lesions in a cohort of referral
      Taiwanese patients.
AB  - INTRODUCTION: A study of the whole spectrum of biopsied head and neck (HN)
      diseases in Taiwan has not yet been performed. Therefore, the current study aimed
      to provide updated information about HN lesions in a cohort of referral Taiwanese
      patients for histopathological examination. METHODS: HN lesions (2000-2011) in
      patients with records of age, sex, and histological diagnoses were retrieved from
      the Oral Pathology Department of the institution. These lesions were classified
      into four main categories: tumor/tumor-like reactive lesions, cystic/pseudocystic
      lesions, inflammatory/infective lesions, and others/miscellaneous lesions.
      RESULTS: A total of 37,210 HN lesions were included in the current study. Most of
      these lesions were distributed in the group of tumor/tumor-like reactive lesions,
      followed by the groups of inflammatory/infective lesions, cystic/pseudocystic
      lesions, and others/miscellaneous lesions. Squamous cell carcinoma was the most
      common HN lesion, and was also the most frequent malignant lesion among the
      referral patients. CONCLUSION: It was worthy of note that squamous cell carcinoma
      and oral potentially malignant disorders comprised high percentages of all HN
      lesions for the present cohort of referral patients.

PMID- 25047218
TI  - PLS-DA wavenumber selection for the categorization of medicine samples based on
      multiple criteria.
AB  - ATR-FTIR spectra may include a large number of noisy and correlated wavenumbers
      that tend to affect and reduce the performance of exploratory and classificatory
      multivariate techniques. We propose a method based on Partial Least Square
      Discriminant Analysis (PLS-DA) for identifying the relevant subsets of ATR-FTIR
      wavenumbers aimed at classifying Viagra and Cialis into authentic or fraudulent
      categories. In our propositions, the PLS-DA is applied to ATR-FTIR data, and four
      indices aimed at evaluating wavenumber importance are derived from PLS-DA
      parameters. Next, an iterative wavenumber elimination and classification
      procedure integrating PLS-DA and the proposed indices is carried out: the
      wavenumber with the smallest index is removed, and a new classification is
      performed using the remaining wavenumbers. The classification performance is
      assessed through multiple criteria, i.e., sensitivity, specificity and percent of
      wavenumbers retained; the recommended wavenumber subset is chosen based on the
      distance between the candidate subsets and a hypothetical ideal solution. The
      proposed method significantly reduced the percent of wavenumbers to be assessed,
      and slightly improved classification performance for Viagra and Cialis data when
      compared to classification on all the original wavenumbers. 

PMID- 25047217
TI  - Hydrogen peroxide reactions on cocaine in hair using imaging mass spectrometry.
AB  - Today, forensic hair analysis is considered to be a standard method for
      identifying chronic drug users since information about drug use stored and
      located in hair can cover several months to even years. When interpreting these
      results, one should be aware of all kind of pitfalls. External factors such as
      bleaching might influence the analytical result. Although the effect of hydrogen
      peroxide on cocaine in a solution was described before, it was never investigated
      whether the described reaction products (ecgonine methylester, benzoylecgonine,
      hydroxynorcocaine and dihydroxycocaine) are indeed found on contaminated or user
      hair. Since it is of great importance in forensic hair analysis to know whether
      cocaine and/or reaction products are detectable in hair after bleaching, matrix
      assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was
      used to study the effect of hydrogen peroxide treatment on incorporated cocaine
      in hairs. Cocaine oxidation products were identified in a solution based on MS/MS
      spectra and spatial distribution of these products in hair was explored using
      MALDI TOF-MS. All images were accomplished by spraying alpha-Cyano-4
      hydroxycinnamic acid (CHCA) as a MALDI-matrix. Images revealed a loss of
      detectability of cocaine and its reaction products in hairs already after a short
      bleaching period. Since all compounds of interest are found in the hydrogen
      peroxide and wash solution, these findings indicate that all evidence of cocaine
      use might be lost after a hair bleaching treatment. Therefore, forensic
      toxicologists should take into consideration whether hair samples were bleached
      before making any conclusions from hair analysis results. 

PMID- 25047219
TI  - Oral fluid as an alternative matrix to determine ethanol for forensic purposes.
AB  - The present work aimed to evaluate whether it is possible to use oral fluid to
      monitor alcohol in drivers. In a control experiment the subjects ingested beer
      with an alcoholic percentage of 4.7%, in an amount that furnished 0.5 g ethanol
      per kg of body weight. Volunteer's urine, oral fluid, and breath were collected
      at 10, 30, 60, and 90 min after alcohol intake. Urine and oral fluid were
      analyzed by gas chromatography with FID (Flame Ionization Detector); breath was
      analyzed by Alcotest 7410 (Drager). The absorption profiles correlated well. The
      Pearson correlation value between samples of oral fluid and urine, and oral fluid
      and exhaled air, was close to 1, showing that oral fluid is a promising matrix to
      monitor drivers in traffic or involved in accidents.

PMID- 25047220
TI  - Studies on the development of latent fingerprints by the method of solid-medium
      ninhydrin.
AB  - A new series of fingerprint developing membrane were prepared using ninhydrin as
      the developing agent, and pressure-sensitive emulsifiers as the encapsulated
      chemicals. The type of emulsifier, plastic film, concentration of the developing
      agent, modifying ions and thickness of the membrane were studied in order to get
      the optimized fingerprint developing effect. The membrane can be successfully
      applied to both latent sweat fingerprints and blood fingerprint on many different
      surfaces. The sensitivity of the method toward the latent sweat fingerprint is
      0.1 mg/L amino acid. The membrane can be applied to both porous and non-porous
      surfaces. Fingerprints that are difficult to develop on surfaces such as leather,
      glass and heat-sensitive paper using traditional chemical methods can be
      successfully developed with this membrane.

PMID- 25047221
TI  - [Bilateral pleural thickening].
AB  - The authors report the case of a 20-year-old man in whom pulmonary and bone
      tuberculosis presented as bilateral pleural thickening without effusion. 

PMID- 25047222
TI  - Litigation seeking access to data from ongoing clinical trials: a threat to
      clinical research.
AB  - Researchers conducting randomized clinical trials may find themselves subject to
      legal subpoenas for interim data. When a subpoena demands premature disclosure of
      unblinded data, there is potential for damage to the scientific integrity and
      reputation of the on-going trial. We describe herein general issues raised by
      subpoenas for trial data and the particular case of a 2012 subpoena served on
      investigators from Yale University who were successful in winning reprieve from
      Connecticut Superior Court. 

PMID- 25047224
TI  - Bioprosthetic mitral valve thrombosis complicating antiphospholipid antibody
      syndrome, successfully treated with thrombolysis.
AB  - The incidence of bioprosthetic valve thrombosis and related embolic complications
      is extremely rare, obviating the need for long-term anticoagulation. As a result,
      experience in the diagnosis and treatment of bioprosthetic valve thrombosis is
      fairly limited. We report the first case of antiphospholipid antibody syndrome
      presenting as bioprosthetic mitral valve thrombosis, 15 months after valve
      replacement, and successfully treated with thrombolytic therapy. 

PMID- 25047225
TI  - Enhanced thermoelectric performance of Cu2CdSnSe4 by Mn doping: experimental and
      first principles studies.
AB  - Serials of Mn doping by substituting Cd sites on Cu2CdSnSe4 are prepared by the
      melting method and the spark plasma sintering (SPS) technique to form Cu2Cd1
      xMnxSnSe4. Our experimental and theoretical studies show that the moderate Mn
      doping by substituting Cd sites is an effective method to improve the
      thermoelectric performance of Cu2CdSnSe4. The electrical resistivity is decreased
      by about a factor of 4 at 723 K after replacing Cd with Mn, but the seebeck
      coefficient decreases only slightly from 356 to 289 MUV/K, resulting in the
      significant increase of the power factor. Although the thermal conductivity
      increases with the doping content of Mn, the figure of merit (ZT) is still
      increased from 0.06 (x = 0) to 0.16 (x = 0.10) at 723 K, by a factor of 2.6. To
      explore the mechanisms behind the experimental results, we have performed an ab
      initio study on the Mn doping effect and find that the Fermi level of Cu2CdSnSe4
      is shifted downward to the valence band, thus improving the hole concentration
      and enhancing the electrical conductivity at the low level doping content.
      Optimizing the synthesis process and scaling Cu2Cd1-xMnxSnSe4 to nanoparticles
      may further improve the ZT value significantly by improving the electrical
      conductivity and enhancing the phonon scattering to decrease the thermal
      conductivity.

PMID- 25047223
TI  - Histone trimethylation at H3K4, H3K9 and H4K20 correlates with patient survival
      and tumor recurrence in early-stage colon cancer.
AB  - BACKGROUND: Post-translational modification of histone tails by methylation plays
      an important role in tumorigenesis. In this study, we investigated the nuclear
      expression of H3K4me3, H3K9me3 and H4K20me3 in early-stage colon cancer in
      relation to clinical outcome. METHODS: Tumor tissue cores of 254 TNM stage I-III
      colorectal cancer patients were immunohistochemically stained for H3K4me3,
      H3K9me3 and H4K20me3 and scored using the semi-automated Ariol system. Cox
      proportional hazard trend analyses were performed to assess the prognostic value
      of the combined markers with respect to patient survival and tumor recurrence.
      RESULTS: The histone methylation markers only showed prognostic value in early
      stage (TNM stage I and II) colon cancer. Therefore, only this patient set (n =
      121) was used for further statistical analyses. Low nuclear expression of
      H3K4me3, and high expression of H3K9me3 and H4K20me3 were associated with good
      prognosis. In combined marker analyses, the patient group showing most favorable
      expression (low H3K4me3, high H3K9me3 and high H4K20me3) was associated with the
      best prognosis. Multivariate trend analyses showed significantly increased hazard
      ratios (HR) for each additional marker showing unfavorable expression, as
      compared to the "all favorable" reference group. The HR for disease-free survival
      was 3.81 (1.72-8.45; p = 0.001), for locoregional recurrence-free survival 2.86
      (1.59-5.13; p < 0.001) and for distant recurrence-free survival 2.94 (1.66-5.22;
      p < 0.001). CONCLUSIONS: Combined nuclear expression of histone modifications
      H3K4me3, H3K9me3 and H4K20me3 is prognostic in early-stage colon cancer. The
      combination of expression of the three histone modifications provides better
      stratification of patient groups as compared to the individual markers and
      provides a good risk assessment for each patient group.

PMID- 25047226
TI  - Efficient amplitude-modulated pulses for triple- to single-quantum coherence
      conversion in MQMAS NMR.
AB  - The conversion between multiple- and single-quantum coherences is integral to
      many nuclear magnetic resonance (NMR) experiments of quadrupolar nuclei. This
      conversion is relatively inefficient when effected by a single pulse, and many
      composite pulse schemes have been developed to improve this efficiency. To
      provide the maximum improvement, such schemes typically require time-consuming
      experimental optimization. Here, we demonstrate an approach for generating
      amplitude-modulated pulses to enhance the efficiency of the triple- to single
      quantum conversion. The optimization is performed using the SIMPSON and MATLAB
      packages and results in efficient pulses that can be used without experimental
      reoptimisation. Most significant signal enhancements are obtained when good
      estimates of the inherent radio-frequency nutation rate and the magnitude of the
      quadrupolar coupling are used as input to the optimization, but the pulses appear
      robust to reasonable variations in either parameter, producing significant
      enhancements compared to a single-pulse conversion, and also comparable or
      improved efficiency over other commonly used approaches. In all cases, the ease
      of implementation of our method is advantageous, particularly for cases with low
      sensitivity, where the improvement is most needed (e.g., low gyromagnetic ratio
      or high quadrupolar coupling). Our approach offers the potential to routinely
      improve the sensitivity of high-resolution NMR spectra of nuclei and systems that
      would, perhaps, otherwise be deemed "too challenging". 

PMID- 25047227
TI  - Body composition and weight gain in new users of the three-monthly injectable
      contraceptive, depot-medroxyprogesterone acetate, after 12 months of follow-up.
AB  - OBJECTIVES: To evaluate weight gain and body composition (BC) in new users of
      depot-medroxyprogesterone acetate (DMPA) as a contraceptive. METHODS: This cohort
      study followed up 20 DMPA users and 20 copper intrauterine device (TCu380A IUD)
      users, paired for age (+/- 1 year) and body mass index (BMI +/- 1 kg/m(2)),
      during 12-months. Healthy, non-obese women aged 18 to 40 years, unaffected by
      conditions that could influence their body weight, were enrolled. Socio
      demographic variables, habits, weight, BMI, BC using dual-energy X-ray
      absorptiometry, circumferences, skinfold thickness, body fat percentage and waist
      to-hip ratio were evaluated. All participants were encouraged to adopt healthy
      habits. RESULTS: At baseline, median age was 29 and 30.5 years, and mean BMI was
      24.8 and 24.5 kg/m(2) in the DMPA and IUD groups, respectively. At 12 months, an
      increase was observed in waist and hip circumference in the DMPA users and 8/20
      of them had a weight gain >= 5% (mean 4.6 kg) with accumulation of fat centrally.
      CONCLUSIONS: There were no differences in weight gain or in BC measurements
      between the groups; nevertheless 40% of women in the DMPA group had larger weight
      gain and accumulation of fat centrally. The duration of follow-up may have been
      insufficient to detect differences between the groups.

PMID- 25047229
TI  - Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.
AB  - Cardiomyopathies have been rarely described in rabbits. Here we report myocardial
      necrosis of the ventricular wall in rabbits with experimentally induced rabies.
      Myocardial lesions were found only in rabbits with brain lesions, and the
      severity of the cardiac lesions was proportional to that of the brain lesions.
      Neither the frequency nor the cumulative dose of anesthesia was related to the
      incidence or the severity of the myocardial lesions. The myocardial lesions were
      characterized by degeneration and/or necrosis of myocardial cells and were
      accompanied by contraction band necrosis, interstitial fibrosis, and infiltration
      of inflammatory cells. The brain lesions due to rabies virus infection were most
      prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla.
      Rabies virus antigen was not found in the hearts of any rabbits. Based on these
      findings, the myocardial lesions were classified as neurogenic cardiomyopathy.

PMID- 25047228
TI  - Feline chronic kidney disease is associated with upregulation of transglutaminase
      2: a collagen cross-linking enzyme.
AB  - Chronic kidney disease is a major cause of morbidity and mortality in cats.
      Transglutaminase 2 (TG2) is a calcium-dependent enzyme proposed to mediate
      tubulointerstitial fibrosis in the kidney by cross-linking collagen fibrils.
      Postmortem kidney tissue was obtained from primary renal azotemic (n = 10) and
      nonazotemic (n = 5) cats (14 domestic short hair, 1 Burmese; aged 9-23.7 years).
      Extracellular matrix protein deposition was determined by Masson's trichrome
      staining and collagen immunofluorescence. Total kidney transglutaminase (TG)
      enzyme activity and TG2 protein were measured in tissue homogenates by putrescine
      incorporation and Western blotting. Extracellular TG enzyme activity and TG2
      protein were determined in situ by immunofluorescence, quantified by multiphase
      image analysis. Results were compared using the unpaired Student's t-test with
      Welch's correction. Elevated plasma creatinine, urea, and phosphate
      concentrations were associated with tubulointerstitial fibrosis but not
      glomerular fibrosis. Kidney homogenates from azotemic cats showed a 3-fold higher
      total TG enzyme activity and TG2 protein compared with kidneys from nonazotemic
      cats. Immunofluorescent studies performed in situ confirmed a 3-fold higher
      extracellular TG enzyme activity and TG2 protein in cats with azotemia.
      Tubulointerstitial TG2 showed a positive linear correlation with both renal
      function and tubulointerstitial fibrosis. In conclusion, for cats with azotemia,
      both filtration failure and tubulointerstitial fibrosis were associated with the
      upregulation of TG2, a collagen cross-linking enzyme and the major isoform of
      transglutaminase in the kidney. TG2 may provide a new therapeutic target for
      drugs designed to slow the progression of feline chronic kidney disease.

PMID- 25047230
TI  - Immobilization of superoxide dismutase on Pt-Pd/MWCNTs hybrid modified electrode
      surface for superoxide anion detection.
AB  - Monitoring of reactive oxygen species like superoxide anion (O2(?-)) turns to be
      of increasing significance considering their potential damages to organism. In
      the present work, we fabricated a novel O2(?-) electrochemical sensor through
      immobilizing superoxide dismutase (SOD) onto a Pt-Pd/MWCNTs hybrid modified
      electrode surface. The Pt-Pd/MWCNTs hybrid was synthesized via a facile one-step
      alcohol-reduction process, and well characterized by transmission electron
      microscopy, X-ray photoelectron spectroscopy and X-ray diffraction. The
      immobilization of SOD was accomplished using a simple drop-casting method, and
      the performance of the assembled enzyme-based sensor for O2(?-) detection was
      systematically investigated by several electrochemcial techniques. Thanks to the
      specific biocatalysis of SOD towards O2(?-) and the Pt-Pd/MWCNTs - promoted fast
      electron transfer at the fabricated interface, the developed biosensor exhibits a
      fast, selective and linear amperometric response upon O2(?-) in the concentration
      scope of 40-1550 MUM (R(2)=0.9941), with a sensitivity of 0.601 mA cm(-2) mM(-1)
      and a detection limit of 0.71 MUM (S/N=3). In addition, the favorable
      biocompatibility of this electrode interface endows the prepared biosensor with
      excellent long-term stability (a sensitivity loss of only 3% over a period of 30
      days). It is promising that the proposed sensor will be utilized as an effective
      tool to quantitatively monitor the dynamic changes of O2(?-) in biological
      systems.

PMID- 25047231
TI  - Measurement of special nanoparticle structures by light scattering.
AB  - The characterization of nanoparticle size and structure by means of classical
      light scattering measurements from monodisperse suspensions is examined from both
      the Rayleigh-Gans (R-G) approximation as well as (for various spherical
      structures) the exact Lorenz-Mie theory. A means by which the traditional limits
      of the R-G theory may be extended and simplified is shown by a detailed
      discussion of the characteristic mean-square radius. This becomes particularly
      important for irregular particle shapes, where scattering depends on the
      orientation of such particles with respect to the direction of the incident
      illumination. A variety of particle structures are addressed, including rods,
      tubes, ellipsoids, rings, and superellipsoids. 

PMID- 25047232
TI  - Ultrastructure and molecular phylogeny of Mesodinium coatsi sp. nov., a benthic
      marine ciliate.
AB  - Mesodinium is a globally distributed ciliate genus forming frequent and recurrent
      blooms in diverse marine habitats. Here, we describe a new marine species,
      Mesodinium coatsi n. sp., originally isolated from interstitial water of surface
      sand samples collected at Mohang Beach, Korea. The species was maintained under a
      mixotrophic growth condition for longer than 1 yr by providing a cryptomonad,
      Chroomonas sp., as the sole prey. Cell morphology and subcellular structure were
      examined by light microscopy, scanning, and transmission electron microscopy, and
      molecular phylogeny was inferred from nuclear-encoded 18S rDNA sequence data.
      Like other Mesodinium species, M. coatsi consisted of two hemispheres separated
      by two types of kinetids, and had tentacles located at the oral end of the cell.
      Several food vacuoles were observed in the cytoplasm, and partially digested prey
      cells sometimes existed in food vacuoles. Kinetids and the associated accessory
      structures were quite similar to those previously reported, but M. coatsi was
      differentiated from other marine Mesodinium species by ultrastructural characters
      of the dikinetids, polykinetids, and tentacles. We also provided a detailed
      illustration of infraciliature. Molecular phylogeny revealed that M. coatsi and
      Mesodinium chamaeleon were closely related to each other. 

PMID- 25047233
TI  - TGFbeta inhibition prior to hypofractionated radiation enhances efficacy in
      preclinical models.
AB  - The immune infiltrate in colorectal cancer has been correlated with outcome, such
      that individuals with higher infiltrations of T cells have increased survival
      independent of the disease stage. For patients with lower immune infiltrates,
      overall survival is limited. Because the patients with colorectal cancer studied
      have received conventional cancer therapies, these data may indicate that the
      pretreatment tumor environment increases the efficacy of treatments such as
      chemotherapy, surgery, and radiotherapy. This study was designed to test the
      hypothesis that an improved immune environment in the tumor at the time of
      treatment will increase the efficacy of radiotherapy. We demonstrate that
      inhibition of TGFbeta using the orally available small-molecule inhibitor SM16
      improved the immune environment of tumors in mice and significantly improved the
      efficacy of subsequent radiotherapy. This effect was not due to changes in
      radiosensitivity, epithelial-mesenchymal transition, or changes in vascular
      function in the tumor; rather, this effect was dependent on adaptive immunity and
      resulted in long-term protective immunity in cured mice. These data demonstrate
      that immunotherapy is an option to improve the immune status of patients with
      poor tumor infiltrates and that pretreatment improves the efficacy of
      radiotherapy.

PMID- 25047234
TI  - Attribution and expression of incentive salience are differentially signaled by
      ultrasonic vocalizations in rats.
AB  - During Pavlovian incentive learning, the affective properties of rewards are
      thought to be transferred to their predicting cues. However, how rewards are
      represented emotionally in animals is widely unknown. This study sought to
      determine whether 50-kHz ultrasonic vocalizations (USVs) in rats may signal such
      a state of incentive motivation to natural, nutritional rewards. To this end,
      rats learned to anticipate food rewards and, across experiments, the current
      physiological state (deprived vs. sated), the type of learning mechanism
      recruited (Pavlovian vs. instrumental), the hedonic properties of UCS (low vs.
      high palatable food), and the availability of food reward (continued vs.
      discontinued) were manipulated. Overall, we found that reward-cues elicited 50
      kHz calls as they were signaling a putative affective state indicative of
      incentive motivation in the rat. Attribution and expression of incentive
      salience, however, seemed not to be an unified process, and could be teased apart
      in two different ways: 1) under high motivational state (i.e., hunger), the
      attribution of incentive salience to cues occurred without being expressed at the
      USVs level, if reward expectations were higher than the outcome; 2) in all
      experiments when food rewards were devalued by satiation, reward cues were still
      able to elicit USVs and conditioned anticipatory activity although reward seeking
      and consumption were drastically weakened. Our results suggest that rats are
      capable of representing rewards emotionally beyond apparent, immediate
      physiological demands. These findings may have translational potential in
      uncovering mechanisms underlying aberrant and persistent motivation as observed
      in drug addiction, gambling, and eating disorders. 

PMID- 25047235
TI  - Anonymous three-party password-authenticated key exchange scheme for Telecare
      Medical Information Systems.
AB  - Telecare Medical Information Systems (TMIS) provide an effective way to enhance
      the medical process between doctors, nurses and patients. For enhancing the
      security and privacy of TMIS, it is important while challenging to enhance the
      TMIS so that a patient and a doctor can perform mutual authentication and session
      key establishment using a third-party medical server while the privacy of the
      patient can be ensured. In this paper, we propose an anonymous three-party
      password-authenticated key exchange (3PAKE) protocol for TMIS. The protocol is
      based on the efficient elliptic curve cryptosystem. For security, we apply the pi
      calculus based formal verification tool ProVerif to show that our 3PAKE protocol
      for TMIS can provide anonymity for patient and doctor while at the same time
      achieves mutual authentication and session key security. The proposed scheme is
      secure and efficient, and can be used in TMIS. 

PMID- 25047236
TI  - Gluten quality of bread wheat is associated with activity of RabD GTPases.
AB  - In the developing endosperm of bread wheat (Triticum aestivum), seed storage
      proteins are produced on the rough endoplasmic reticulum (ER) and transported to
      protein bodies, specialized vacuoles for the storage of protein. The functionally
      important gluten proteins of wheat are transported by two distinct routes to the
      protein bodies where they are stored: vesicles that bud directly off the ER and
      transport through the Golgi. However, little is known about the processing of
      glutenin and gliadin proteins during these steps or the possible impact on their
      properties. In plants, the RabD GTPases mediate ER-to-Golgi vesicle transport.
      Available sequence information for Rab GTPases in Arabidopsis, rice, Brachypodium
      and bread wheat was compiled and compared to identify wheat RabD orthologs.
      Partial genetic sequences were assembled using the first draft of the Chinese
      Spring wheat genome. A suitable candidate gene from the RabD clade (TaRabD2a) was
      chosen for down-regulation by RNA interference (RNAi), and an RNAi construct was
      used to transform wheat plants. All four available RabD genes were shown by qRT
      PCR to be down-regulated in the transgenic developing endosperm. The transgenic
      grain was found to produce flour with significantly altered processing properties
      when measured by farinograph and extensograph. SE-HPLC found that a smaller
      proportion of HMW-GS and large proportion of LMW-GS are incorporated into the
      glutenin macropolymer in the transgenic dough. Lower protein content but a
      similar protein profile on SDS-PAGE was seen in the transgenic grain. 

PMID- 25047237
TI  - Individually tailored ultrasound-assisted prompted voiding for institutionalized
      older adults with urinary incontinence.
AB  - OBJECTIVES: To assess individually tailored ultrasound-assisted prompted voiding
      as a means of managing urinary incontinence in hospitalized elderly patients.
      METHODS: A total of 88 incontinent elderly individuals who were inpatients in
      general hospitals were included. Each individual's mean bladder volume before
      starting to void (voided urine volume plus residual urine volume) was regarded as
      the optimal bladder volume. Bladder volume was regularly monitored with an
      ultrasound device, and when the urine volume had reached the individual's optimal
      bladder volume, the subject was prompted to void. The outcomes were evaluated on
      the basis of scores on a four-grade scale for items in six domains: urine volume,
      voiding function, urinary control, physical and cognitive function for toileting,
      and caregivers' burden in regard to continence care. The score for use of a
      pad/diaper, an item of urinary control domain, was used as the primary outcome
      measure. RESULTS: A total of 80 participants were included for analysis. After
      ultrasound-assisted prompted voiding care for a 4-week period, the score for use
      of a pad/diaper in 50 out of 80 participants (62.5%) had decreased, and 21 out of
      80 participants (26.3%) no longer required the use of a pad/diaper at all. The
      scores of the other 30 out of 80 participants (37.5%) were unchanged. The
      improvement was not significantly affected by patients' backgrounds at baseline.
      The mean scores in the domains of urinary control, physical function, cognitive
      function and caregivers' burden improved significantly. CONCLUSION: The present
      preliminary study suggests that individually tailored ultrasound-assisted
      prompted voiding can improved urinary incontinence of institutionalized elderly
      patients. Further studies are worth carrying out.

PMID- 25047238
TI  - Incidence of second malignancies for prostate cancer.
AB  - INTRODUCTION: There is a need to assess risk of second primary cancers in
      prostate cancer (PCa) patients, especially since PCa treatment may be associated
      with increased risk of second primary tumours. METHODS: We calculated
      standardized incidence ratios (SIRs) for second primary tumours comparing men
      diagnosed with PCa between 1980 and 2010 in the Canton of Zurich, Switzerland (n
      = 20,559), and the general male population in the Canton. RESULTS: A total of
      1,718 men developed a second primary tumour after PCa diagnosis, with lung and
      colon cancer being the most common (15 and 13% respectively). The SIR for overall
      second primary cancer was 1.11 (95%CI: 1.06-1.17). Site-specific SIRs varied from
      1.19 (1.05-1.34) to 2.89 (2.62-4.77) for lung and thyroid cancer, respectively.
      When stratified by treatment, the highest SIR was observed for thyroid cancer
      (3.57 (1.30-7.76)) when undergoing surgery, whereas liver cancer was common when
      treated with radiotherapy (3.21 (1.54-5.90)) and kidney bladder was most
      prevalent for those on hormonal treatment (3.15 (1.93-4.87)). Stratification by
      time since PCa diagnosis showed a lower risk of cancer for men with PCa compared
      to the general population for the first four years, but then a steep increase in
      risk was observed. CONCLUSION: In the Canton of Zurich, there was an increased
      risk of second primary cancers among men with PCa compared to the general
      population. Increased diagnostic activity after PCa diagnosis may partly explain
      increased risks within the first years of diagnosis, but time-stratified analyses
      indicated that increased risks remained and even increased over time.

PMID- 25047239
TI  - Community pharmacy type 2 diabetes risk assessment: demographics and risk
      results.
AB  - OBJECTIVES: To determine the demographics and risk results of patients accessing
      a community pharmacy diabetes risk assessment service. METHOD: Participating
      patients underwent an assessment using a validated questionnaire to determine
      their 10-year risk of developing type 2 diabetes. Patients were given appropriate
      lifestyle advice or referred to their general practitioner if necessary. KEY
      FINDINGS: In total, 21 302 risk assessments were performed. Nearly one-third
      (29%) of 3427 risk assessments analysed yielded a result of moderate or high
      chance of developing the condition. CONCLUSIONS: Community pharmacies can
      identify a significant number of patients at risk of developing type 2 diabetes
      in the next 10 years. Further follow-up work needs to be done to determine the
      cost-effectiveness of such a service and the consequences of receiving a risk
      assessment.

PMID- 25047240
TI  - Enhanced levels of nicotianamine promote iron accumulation and tolerance to
      calcareous soil in soybean.
AB  - Iron (Fe) is an essential nutrient in both plants and humans. Fe deficiency on
      calcareous soil with low Fe availability is a major agricultural problem.
      Nicotianamine (NA) is one of the Fe chelator in plants, which is involved in
      metal translocation into seeds, and serves as an antihypertensive substance in
      humans. In this study, soybean plants overexpressing the barley NA synthase 1
      (HvNAS1) gene driven by the constitutive CaMV 35S promoter were produced using
      Agrobacterium-mediated transformation. The transgenic soybean showed no growth
      defect and grew normally. The NA content of transgenic soybean seeds was up to
      four-fold greater than that of non-transgenic (NT) soybean seeds. The level of
      HvNAS1 expression was positively correlated with the amount of NA, and a high
      concentration of NA was maintained in the seeds in succeeding generations. The Fe
      concentration was approximately two-fold greater in transgenic soybean seeds than
      in NT soybean seeds. Furthermore, the transgenic soybeans showed tolerance to low
      Fe availability in calcareous soil. Our results suggested that increasing the NA
      content in soybean seeds by the overexpression of HvNAS1 offers potential
      benefits for both human health and agricultural productivity. 

PMID- 25047242
TI  - Total synthesis of isoquinocyclinone.
AB  - The total synthesis of the heptacyclic natural product isoquinocyclinone has been
      achieved. A Hauser annulation was used to assemble the anthraquinone core
      structure. The unique 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole substructure was
      prepared by alkyne addition to a lactone intermediate and subsequent Ni(0) 
      mediated cyanide addition, the conversion of an O,O- into an N,O-acetal, and
      final intramolecular N-alkylation. 

PMID- 25047241
TI  - Prevalence of type 2 diabetes among high-risk adults in Shanghai from 2002 to
      2012.
AB  - OBJECTIVE: The objective of this study was to evaluate the trend and prevalence
      of prediabetes and diabetes among high-risk adults in Shanghai from 2002 to 2012.
      METHODS: From 2002 to 2012, 10043 subjects with known risk factors for diabetes
      participated in the diabetes-screening project at the Shanghai Sixth People's
      Hospital of Shanghai Jiao Tong University. All participants were asked to
      complete a nurse-administered standard questionnaire concerning age, sex, smoking
      status, and personal and family histories of diabetes, cardiovascular disease,
      stroke, hypertension and other diseases. The participants' body mass index
      scores, blood pressures and blood glucose levels at 0, 30, 60, 120 and 180 min
      were measured in response to a 75 g oral glucose tolerance test. RESULTS: The
      overall prevalence of diabetes increased from 27.93% to 34.78% between 2002 and
      2012 in high-risk subjects. The study also showed that the prevalence increased
      much faster in male compared to female subjects. Specifically, an increased rate
      was seen in middle-aged men, with no change observed in middle-aged females over
      the eleven-year period. CONCLUSION: This study showed that sex, age, parental
      diabetic history, and being overweight were associated with an increased risk for
      diabetes in high-risk people. Therefore, as prediabetes and diabetes are highly
      prevalent in people with multiple diabetes risk factors in Shanghai, screening
      programs targeting these individuals may be beneficial.

PMID- 25047243
TI  - Evaluation of different obesity indices as predictors of type 2 diabetes mellitus
      in a Chinese population.
AB  - BACKGROUND: The aim of the present study was to compare correlation coefficients
      between anthropometric indices and blood glucose level, and to determine optimal
      cutoff points of obesity indices in a Chinese population. METHODS: 2419 males and
      5140 females participated in this study in Changchun city. Weight, height, WC
      (waist circumference) and hip circumference were measured; and BMI (body mass
      index), WHtR (waist height ratio), WHR (waist hip ratio) and BAI (body adiposity
      index) were calculated by formulas. FPG (fasting plasma glucose), PPG (post-load
      plasma glucose), HbA1c (glycosylated hemoglobin) and FSI (fasting serum insulin)
      were measured. RESULTS: WHtR had the highest partial correlation coefficients
      with blood glucose and HbA1c in both males and females; however, BAI had the
      lowest coefficients. AUC (area under receiver operating characteristic curves)
      for WHtR in screening type 2 diabetes mellitus were higher than other indices. We
      confirmed that the optimal cutoff points of obesity for WHtR, WHR, WC, BMI and
      BAI were 0.55, 0.92, 88.1, 25.9 and 28.1 in males, and 0.52, 0.85, 81.6, 24.6 and
      31.0 in females, respectively. CONCLUSIONS: Central obesity correlates more
      closely to glucose metabolism in Chinese population than general obesity. WHtR is
      the best index to predict type 2 diabetes mellitus in Chinese adults.

PMID- 25047244
TI  - Feature issue: visual function and the ageing visual system.

PMID- 25047245
TI  - A pilot randomised controlled trial of Problem-Solving Treatment for Visual
      Impairment (POSITIVE): protocol paper.
AB  - PURPOSE: For visually impaired individuals, motivation to be mobile and the
      individual's emotional states are predetermining factors of functioning. In
      addition, loss of confidence at the time of diagnosis could inhibit the ability
      to make progress. The aim of this study is to evaluate whether Problem-Solving
      Treatment, a brief, structured psychological intervention, leads to better
      psychological well-being in people who have been recently diagnosed as blind or
      partially sighted. METHODS: A pilot randomised controlled trial: the trial aims
      to recruit 120 individuals who have either: (1) been diagnosed with severe,
      irreversible sight loss, or (2) registered as blind or partially sighted within
      the last 3 months. Individuals will be randomly allocated to either the
      intervention or control group with randomisation stratified by severity of vision
      loss. Those in the intervention arm will receive Problem-Solving Treatment, an
      established intervention that addresses individual's confidence, motivation and
      psychological well-being by undertaking specific tasks to help individuals work
      through their problems, and recognising steps to problem resolution. Both groups
      will continue to receive routine care, such as mobility training. STUDY OUTCOMES:
      The primary outcome is psychological well-being measured at 3, 6, and 9 months
      after recruitment and assignment to intervention or control group. Secondary
      outcomes include symptoms of distress, mobility and quality of life.

PMID- 25047247
TI  - Are fibromyalgia patients cognitively impaired? Objective and subjective
      neuropsychological evidence.
AB  - OBJECTIVE: Patients with fibromyalgia (FM) syndrome often report a cluster of
      cognitive disorders that strongly interferes with their work and daily life, but
      the relationship between impaired cognitive function and self-reported
      dysfunction remains unclear. We aimed to investigate the presence of cognitive
      impairments in patients with FM and to analyze the relationship between the
      impairments and their evaluation by the patients through a comparison with a
      group of healthy controls. METHODS: In total, 30 FM patients and 30 healthy
      controls performed a neuropsychological and clinical evaluation of short-term,
      long-term, and working memory; executive function; and self-evaluation of
      cognitive impairment and depressive and anxiety symptoms. To thoroughly
      investigate executive function, we adopted the Miyake model that identifies 4
      domains: shifting, inhibition, updating, and access. RESULTS: Our results
      confirmed the presence of impairments of attention, long-term memory, working
      memory, and shifting and updating executive functions in FM patients compared
      with healthy controls. These impairments are reflected in patient reports
      independently of depressive symptoms. CONCLUSION: The use of a self-reported
      questionnaire in clinical practice would provide a first and easy screen for the
      presence of cognitive impairment in FM patients and, in most cases, obviate the
      need for a time-consuming full neuropsychological test battery.

PMID- 25047246
TI  - Bio-inspired cryo-ink preserves red blood cell phenotype and function during
      nanoliter vitrification.
AB  - Current red-blood-cell cryopreservation methods utilize bulk volumes, causing
      cryo-injury of cells, which results in irreversible disruption of cell
      morphology, mechanics, and function. An innovative approach to preserve human red
      blood-cell morphology, mechanics, and function following vitrification in
      nanoliter volumes is developed using a novel cryo-ink integrated with a
      bioprinting approach. 

PMID- 25047248
TI  - New national clinical trials network faces challenges: budget cuts and enrollment
      caps have group leaders concerned.

PMID- 25047249
TI  - New findings in colon cancer incidence, screening.

PMID- 25047250
TI  - Twice-daily pill could treat leukemia.

PMID- 25047251
TI  - Introduction to adolescent and young adult series.

PMID- 25047253
TI  - Morphological assessment of ancestry using cranial macromorphoscopics.
AB  - Ancestry estimation is essential for biological profile estimation in forensic
      anthropology. Hefner (2009) and Osteoware (Smithsonian Institution, 2011)
      presented 16 macromorphoscopic traits that can be scored for standardized data
      collection and can also be used within a statistical framework to estimate
      ancestry. The primary purpose of this research was to examine the utility of
      these traits for assessing ancestry. Tests of observer agreement and the range of
      variation in trait expression were evaluated. A sample of 208 American whites and
      blacks from the Hamann-Todd Collection were scored, and several classification
      methods were utilized in accordance with Hefner (2009). Correct classifications
      for the pooled sex analyses ranged from 73.3% to 86.6% and from 46.7% to 64.3%
      when the sexes were analyzed independently. Interobserver agreement was variable
      and was found to be lower than that presented in Hefner (2009). Trait expression
      was variable in both groups and was generally consistent with Hefner's findings. 

PMID- 25047252
TI  - Prevention of murine lupus nephritis by targeting multiple signaling axes and
      oxidative stress using a synthetic triterpenoid.
AB  - OBJECTIVE: Current treatment options for lupus are far from optimal. Previously,
      we reported that phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin,
      MEK-1/ERK-1,2, p38, STAT-3, STAT-5, NF-kappaB, multiple Bcl-2 family members, and
      various cell cycle molecules were overexpressed in splenic B cells in an age
      dependent and gene dose-dependent manner in mouse strains with spontaneous lupus.
      Since the synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate
      (CDDO-Me) has been shown to inhibit AKT, MEK-1/2, and NF-kappaB, and to induce
      caspase-mediated apoptosis, we tested the therapeutic potential of this agent in
      murine lupus nephritis. METHODS: The synthetic triterpenoid CDDO-Me or placebo
      was administered to 2-month-old B6.Sle1.Sle3 mice or MRL/lpr mice, which develop
      spontaneous lupus. All mice were phenotyped for disease. RESULTS: CDDO-Me-treated
      mice exhibited significantly reduced splenic cellularity, with decreased numbers
      of both CD4+ T cells and activated CD69+/CD4+ T cells compared to the placebo
      treated mice. These mice also exhibited a significant reduction in serum
      autoantibody levels, including anti-double-stranded DNA (anti-dsDNA) and
      antiglomerular antibodies. Finally, CDDO-Me treatment attenuated renal disease in
      mice, as indicated by reduced 24-hour proteinuria, blood urea nitrogen, and
      glomerulonephritis. At the mechanistic level, CDDO-Me treatment dampened MEK-1/2,
      ERK, and STAT-3 signaling within lymphocytes and oxidative stress. Importantly,
      the NF-E2-related factor 2 pathway was activated after CDDO-Me treatment,
      indicating that CDDO-Me may modulate renal damage in lupus via the inhibition of
      oxidative stress. CONCLUSION: These findings underscore the importance of AKT/MEK
      1/2/NF-kappaB signaling in engendering murine lupus. Our findings indicate that
      the blockade of multiple signaling nodes and oxidative stress may effectively
      prevent and reverse the hematologic, autoimmune, and pathologic manifestations of
      lupus.

PMID- 25047254
TI  - Mathematical modelling of glycosaminoglycan production by stem cell aggregates
      incorporated with growth factor-releasing polymer microspheres.
AB  - Systems composed of high density cells incorporated with growth factor-releasing
      polymer microspheres have recently been shown to promote chondrogenic
      differentiation and cartilage formation. Within these systems, the effects of
      spatial and temporal patterning of growth factor release on hyaline cartilage
      specific extracellular matrix production have been examined. However, at present,
      it is unclear which microsphere densities and growth factor delivery profiles are
      optimal for inducing human mesenchymal stem cell differentiation and
      glycosaminoglycan production. A mathematical model to describe glycosaminoglycan
      production as a function of initial microsphere loading and microsphere
      degradation rate over a period of 3 weeks is presented. Based on predictions
      generated by this model, it may be feasible to design a bioactive microsphere
      system with specific spatiotemporal growth factor presentation characteristics to
      promote glycosaminoglycan production at controllable rates. Copyright (c) 2014
      John Wiley & Sons, Ltd.

PMID- 25047255
TI  - Re-establishment of the genus Ania Lindl. (Orchidaceae).
AB  - Ania Lindl. is a small genus of the tribe Collabieae subtribe Collabiinae
      (Orchidaceae). For the last 150 years, it has generally been treated as a synonym
      of Tainia Blume. In this study, we critically re-examined morphological
      characters that have been used to distinguish Ania from Tainia, and assessed the
      phylogeny of Tainia using morphological and palynological characters. Sequences
      of the nuclear ribosomal ITS, chloroplast trnL intron and combined DNA data sets
      were analysed to clarify the delimitation and the phylogeny of these groups. The
      morphological and palynological survey revealed a number of useful diagnostic
      characters which permit a clear definition of Ania, after the exclusion of a
      single taxonomically questionable species. Results confirmed that Ania is
      distinct from Tainia. Phylogenetic reconstructions based on molecular data
      provided the greatest resolution and produced a morphologically well
      differentiated clade of Ania. In addition to morphological and suggested
      palynological characters, the phylogenies were also supported by karyological
      evidence. Our results support the independent generic status of Ania. The genus
      name Ania is revived and re-established. 

PMID- 25047256
TI  - Nanomedicine scale-up technologies: feasibilities and challenges.
AB  - Nanomedicine refers to biomedical and pharmaceutical applications of nanosized
      cargos of drugs/vaccine/DNA therapeutics including nanoparticles, nanoclusters,
      and nanospheres. Such particles have unique characteristics related to their
      size, surface, drug loading, and targeting potential. They are widely used to
      combat disease by controlled delivery of bioactive(s) or for diagnosis of life
      threatening problems in their very early stage. The bioactive agent can be
      combined with a diagnostic agent in a nanodevice for theragnostic applications.
      However, the formulation scientist faces numerous challenges related to their
      development, scale-up feasibilities, regulatory aspects, and commercialization.
      This article reviews recent progress in the method of development of
      nanoparticles with a focus on polymeric and lipid nanoparticles, their scale-up
      techniques, and challenges in their commercialization.

PMID- 25047257
TI  - Surface-confined self-assembled Janus tectons: a versatile platform towards the
      noncovalent functionalization of graphene.
AB  - A general strategy for simultaneously generating surface-based supramolecular
      architectures on flat sp(2) -hybridized carbon supports and independently
      exposing on demand off-plane functionality with controlled lateral order is
      highly desirable for the noncovalent functionalization of graphene. Here, we
      address this issue by providing a versatile molecular platform based on a library
      of new 3D Janus tectons that form surface-confined supramolecular adlayers in
      which it is possible to simultaneously steer the 2D self-assembly on flat
      C(sp(2))-based substrates and tailor the external interface above the substrate
      by exposure to a wide variety of small terminal chemical groups and functional
      moieties. This approach is validated throughout by scanning tunneling microscopy
      (STM) at the liquid-solid interface and molecular mechanics modeling studies. The
      successful self-assembly on graphene, together with the possibility to transfer
      the graphene monolayer onto various substrates, should considerably extend the
      application of our functionalization strategy.

PMID- 25047258
TI  - How to submit MS proteomics data to ProteomeXchange via the PRIDE database.
AB  - The ProteomeXchange (PX) consortium has been established to standardize and
      facilitate submission and dissemination of MS-based proteomics data in the public
      domain. In the consortium, the PRIDE database at the European Bioinformatics
      Institute, acts as the initial submission point of MS/MS data sets. In this
      manuscript, we explain step by step the submission process of MS/MS data sets to
      PX via PRIDE. We describe in detail the two available workflows: 'complete' and
      'partial' submissions, together with the available tools to streamline the
      process. Throughout the manuscript, we will use one example data set containing
      identification and quantification data, which has been deposited in
      PRIDE/ProteomeXchange with the accession number PXD000764
      (http://proteomecentral.proteomexchange.org/dataset/PXD000764). 

PMID- 25047259
TI  - Fluid responsiveness is about stroke volume, and not pulse pressure Yogi: the
      power of Doppler fluid management and cardiovascular monitoring.
AB  - Fluid infusion is one of the most common critical care interventions, yet
      approximately 50% of all fluid interventions are unnecessary and potentially
      harmful. An improved approach to identification of fluid responsiveness is of
      clinical importance. Currently fluid responsiveness is most frequently identified
      by blood pressure (BP) measurements or a surrogate. However fluid responsiveness
      is simply the increase in stroke volume (SV) associated with volume expansion,
      and may not be reflected in BP or BP surrogates. Guyton demonstrated that
      BP=COxSVR, and it is know that baroreceptor mediated autonomic nervous system
      regulation of SV and SVR to preserve BP may mask significant and critical changes
      in haemodynamics. Dr Pinsky in his recent J Clin Monit Comput Editorial evaluated
      the relative merits of pulse pressure variability (PPV) methods, a variant on BP
      measurement, for assessment of fluid responsiveness and promoted the use of
      physiologic challenges to augment the applicability of PPV. However this guidance
      is only half right. This letter reminds clinicians of the physiologic limitations
      of PPV as a measure of fluid responsiveness, even when combined with physiologic
      challenges, and recommends the replacement of BP with SV measurements. The
      combination of accurate Doppler measurement of SV and physiologic challenges, as
      Dr Pinsky recommends, is a physiologically rational and effective approach to
      identification of fluid responsiveness with established evidence. The direct
      monitoring of SV and SV changes has the potential to improve a long standing
      critical care and anaesthetic conundrum; when to give fluid and when to stop.

PMID- 25047260
TI  - Effect of simulated microwave disinfection on the linear dimensional change,
      hardness and impact strength of acrylic resins processed by different
      polymerization cycles.
AB  - AIM: This study investigated the effect of simulated microwave disinfection (SMD)
      on the linear dimensional changes, hardness and impact strength of acrylic resins
      under different polymerization cycles. METHDOS: Metal dies with referential
      points were embedded in flasks with dental stone. Samples of Classico and Vipi
      acrylic resins were made following the manufacturers' recommendations. The
      assessed polymerization cycles were: A) water bath at 74 oC for 9 h; B) water
      bath at 74 oC for 8 h and temperature increased to 100 oC for 1 h; C) water bath
      at 74 oC for 2 h and temperature increased to 100 oC for 1 h; and D) water bath
      at 120 oC and pressure of 60 pounds. Linear dimensional distances in length and
      width were measured after SMD and water storage at 37 oC for 7 and 30 days using
      an optical microscope. SMD was carried out with the samples immersed in 150 mL of
      water in an oven (650 W for 3 min). A load of 25 gf for 10 s was used in the
      hardness test. Charpy impact test was performed with 40 kpcm. Data were submitted
      to ANOVA and Tukey's test (5%). RESULTS: The Classico resin was dimensionally
      steady in length in the A and D cycles for all periods, while the Vipi resin was
      steady in the A, B and C cycles for all periods. The Classico resin was
      dimensionally steady in width in the C and D cycles for all periods, and the Vipi
      resin was steady in all cycles and periods. The hardness values for Classico
      resin were steady in all cycles and periods, while the Vipi resin was steady only
      in the C cycle for all periods. Impact strength values for Classico resin were
      steady in the A, C and D cycles for all periods, while Vipi resin was steady in
      all cycles and periods. CONCLUSION: SMD promoted different effects on the linear
      dimensional changes, hardness and impact strength of acrylic resins submitted to
      different polymerization cycles when after SMD and water storage were considered.

PMID- 25047261
TI  - Evaluation of scientific production in oral surgery in Italy from 1998 to 2012.
AB  - AIM: Dental research, especially in the field of oral surgery, showed a strong
      and significant increase during the last years. This was probably determined by
      the introduction among the clinicians of different therapeutic protocols through
      biomaterials engineering, and by the large broadcasting of scientific knowledge
      due to new media such as the internet. The aim of this work was to analyze the
      scientific production of a sample of Italian Oral Surgeons from 1998 to 2012.
      METHODS: The scientific production of 252 Active Members belonging to three
      Italian associations of Oral Surgery (SIdCO, SIO, SICOI) was examined. The number
      of authors, the number of publications and the number of citation were quantified
      for three periods of 5 years each from the first year considered along 15 years.
      The overall sample was then divided into two groups, academics and not academics,
      in order to differently assess the scientific production conducted inside or
      outside the University. RESULTS: Over the years, scientific production increased
      considerably, with a progression not strictly proportional if compared to the
      number of authors, especially in the last 5 years. By spearately considering the
      academics and the not academics authors, the biggest contribution to the
      scientific production increasingly came from the last 5 years, both in terms of
      authors' and published papers number. CONCLUSION: The results reported in this
      bibliometric analysis show how scientific research increasingly pursued by
      clinicians in oral surgery in the last 15 years.

PMID- 25047262
TI  - Qualitative and quantitative assessment of plaque bacteria in pediatric patients,
      patients undergoing orthodontic treatment, combined orthdontic-surgical treatment
      and implant-prosthetic rehabilitation.
AB  - AIM: The aim of this paper was to describe the qualitative and quantitative
      changes occurring within the oral bacterial flora of several groups of patients
      following oral prevention protocols during the stages of the dental treatment
      they required. METHODS: Three hundred patients were enrolled in the study. The
      selected patients were categorized into different groups to receive preventive
      strategies according to their needs and treatment required. Plaque samples from
      each patient were collected at different intervals according to the treatment
      they were undergoing. These were then assessed under a microscope to carry out a
      quantitative and qualitative assessment of the plaque. RESULTS: The Mean Plaque
      Index Score of most patients generally decreased during the various treatment
      phases and hence the overall bacterial count. However, we noticed a slight
      increase in the plaque index in patients undergoing orthodontic surgery after
      placement of the orthodontic appliance and patients undergoing combined
      orthodontic-surgical treatment during the intermaxillary fixation phase. We
      generally found that the coccoidal bacterial form was the most prevalent.
      CONCLUSION: Patients who were adequately instructed and motivated through oral
      hygiene prevention strategies, showed a significant decrease in the plaque levels
      and in the overall bacterial components between the first visit and the
      successive sample taking. Even though we noticed a slight increase in the plaque
      index in patients undergoing the intermaxillary fixation phase, this decreased
      immediately once the phase ended and the patients managed to return to the
      routine oral hygiene care. This highlights the importance of constant motivation
      and oral hygiene instruction reinforcement.

PMID- 25047263
TI  - Effects of fluorotherapy on oral changes caused by a vegan diet.
AB  - AIM: The aim of this paper was to investigate the effects of fluorotherapy on the
      oral health of subjects who had been following a vegan diet (lacking in meat and
      animal derivatives) for a long period of time (at least 1 year and 6 months).
      METHODS: A preliminary study (t0) evaluated 50 subjects, all from northern Italy
      and aged 24-60 years (28 male and 22 female) who had been following a vegan diet
      for a minimum of 18 months to a maximum of 20 years, and compared them with a
      control group of 50 individuals following a Mediterranean diet. All vegan
      subjects showed oral changes such as white spots, lesions invisible to the naked
      eye and decreased salivary pH values (~5-6). In a second study (t1), the 50 vegan
      subjects were randomly divided into two subgroups of 25. Subgroup SG1 underwent
      fluorotherapy with sodium fluoride (Elmex fluoride gel(r) 1.25%) administered
      once daily for 1 year. Subgroup SG2 served as controls and did not receive
      fluorotherapy. The following parameters were recorded before the start of
      fluorotherapy and again after 1 year: salivary pH; Decayed, Missing, Filled teeth
      Index; presence and location of white spots and lesions not visible to the naked
      eye; Plaque Index, and Gingival Index. RESULTS: In SG1, larger lesions became
      smaller in diameter and small lesions disappeared, a statistically significant
      improvement compared with SG2, despite the persistence of restricted eating
      habits and the oral hygiene conditions being similar to those at t0. Salivary pH
      showed no significant change in either subgroup. CONCLUSION: Daily application of
      a topical 1.25% fluoride gel is effective in reducing the incidence of white spot
      lesions caused by a vegan diet.

PMID- 25047264
TI  - Increased numbers of bone marrow-derived cells in parathyroid adenoma.
AB  - BACKGROUND: In primary hyperparathyroidism (PHPT), the increased levels of
      parathyroid hormone (PTH) result in mobilisation of bone-marrow-derived cells
      (BMCs) into peripheral blood. However, the fate of these cells is still unknown.
      MATERIALS AND METHODS: In this study, we sought to investigate cells with typical
      surface markers of BMCs within parathyroid adenomas (PA) of patients with primary
      hyperparathyroidism. We therefore investigated PA and normal parathyroid glands
      (NPG) of 15 patients with PHPT by immunohistochemistry and PCR. RESULTS: mRNA
      levels for CD31, CD34 and CD45 were significantly increased in PA compared to
      NPG. Immunohistochemical staining for CD31 and CD34 revealed a significantly
      higher vessel density in PA. Furthermore, scattered single cells expressing CD31,
      CD34 or CD45 were significantly augmented compared to normal parathyroid glands
      and directly correlated with vessel density. mRNA levels of SDF-1 was increased
      whereas its major inhibitor dipeptidylpeptidase IV (DPP IV) is decreased in PA,
      suggesting that the SDF-1 axis plays a role in the migration of BMCs into PA.
      CONCLUSION: These data indicate a possible role of BMCs in the pathophysiology of
      PA of patients with PHPT.

PMID- 25047265
TI  - ZNF367 inhibits cancer progression and is targeted by miR-195.
AB  - BACKGROUND: Several members of the zinc finger protein family have been recently
      shown to have a role in cancer initiation and progression. Zinc finger protein
      367 (ZNF367) is a member of the zinc finger protein family and is expressed in
      embryonic or fetal erythroid tissue but is absent in normal adult tissue.
      METHODOLOGY/PRINCIPAL FINDINGS: We show that ZNF367 is overexpressed in
      adrenocortical carcinoma, malignant pheochromocytoma/paraganglioma and thyroid
      cancer as compared to normal tissue and benign tumors. Using both functional
      knockdown and ectopic overexpression in multiple cell lines, we show that ZNF367
      inhibits cellular proliferation, invasion, migration, and adhesion to
      extracellular proteins in vitro and in vivo. Integrated gene and microRNA
      expression analyses showed an inverse correlation between ZNF367 and miR-195
      expression. Luciferase assays demonstrated that miR-195 directly regulates ZNF367
      expression and that miR-195 regulates cellular invasion. Moreover, integrin alpha
      3 (ITGA3) expression was regulated by ZNF367. CONCLUSIONS/SIGNIFICANCE: Our
      findings taken together suggest that ZNF367 regulates cancer progression.

PMID- 25047266
TI  - [Medical habilitation in German-speaking countries : Quantitative assessment of
      content and elaboration of habilitation guidelines].
AB  - BACKGROUND: Habilitation defines the qualification to conduct self-contained
      university teaching and is the key for access to a professorship at German,
      Austrian and Swiss universities. Despite all changes implemented in the European
      higher education systems during the Bologna process, it is the highest
      qualification level issued through the process of an university examination and
      remains the core concept of scientific careers in these countries. In the field
      of medicine, this applies not only to scientific staff at the universities but
      also to those medical doctors aiming at a clinical career track. OBJECTIVES: To
      provide a quantitative analysis of the scientific, didactic, and procedural
      criteria for medical habilitation in German-speaking countries. MATERIALS AND
      METHODS: Based on the guidelines of all 43 medical academic institutions, the
      criteria which candidates are required to fulfil prior to habilitation as well as
      formal requirements related to the habilitation procedure itself have been
      acquired and quantitatively analyzed. RESULTS: Having evaluated all habilitation
      guidelines by means of 87 items, the quantitative analysis revealed significant
      differences in terms of number, kind and scale of criteria stated therein. Most
      habilitation guidelines scarcely define the capabilities applicants have to
      prove: concerning the scientific qualifications on types of publications for
      instance, no item was mentioned in more than half of all habilitation guidelines.
      CONCLUSION: Based on this data analysis, the authors discuss the related
      literature and describe five main distinguishing areas of habilitation guidelines
      in terms of the set of the formal and procedural framework as well as the
      prequalification and postqualification criteria imposed on habilitation
      candidates. There are therefore substantial differences in the organization of
      the habilitation for medicine.

PMID- 25047267
TI  - Chlorambucil-rituximab as first-line therapy in patients affected by follicular
      non-Hodgkin's lymphoma: a retrospective single-centre study.
AB  - Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, has
      been shown to be active in newly diagnosed and relapsed patients with follicular
      lymphoma (FL), both as monotherapy and in combination with chemotherapy. Many
      studies suggest that the prognosis of patients with FL may improve when it is
      used in combination with chemotherapy. Despite these advances, the disease
      remains essentially incurable with standard therapy, and novel approaches to
      treatment are needed because optimal therapy is not defined. The combination of
      chlorambucil-rituximab is one of several standard treatment options for FL. Here,
      we considered data arising from 75 patients with newly diagnosed FL at the
      European Institute of Oncology treated with the combination of rituximab plus
      chlorambucil. The aim of this study was to evaluate the efficacy and safety of
      chlorambucil and rituximab, delivered 6 mg/m(2) /day orally for 6 weeks and 375
      mg/m(2) in a standard 4-weekly schedule, respectively. Patients responding to the
      induction therapy received a prolonged therapy with four additional cycles of
      chlorambucil plus rituximab. Seventy-one patients (94.6%) completed the
      treatment; four patients discontinued treatment because of grade 3-4
      hematological toxicity. The overall response rate was 97.3% including 74.7% of
      complete responses. Only two patients had a stable disease at revaluation after
      treatment. With a median follow-up of 57 months, 72 patients (96%) are alive.
      Median event-free survival (EFS) and median overall survival (OS) were not
      reached; 5-year OS rate was 98.4%. The 5-year EFS was 71.3%. By univariate and
      multivariate analyses, elevated beta-2 microglobulin levels and partial responses
      to therapy were correlated with worse EFS. These results suggest that the
      combination of chlorambucil and rituximab is an active and safe regimen in
      patients with newly diagnosed FL, principally in those with low tumour burden and
      favourable prognostic factors.

PMID- 25047268
TI  - Low virulence? Clinical characteristics of Raoultella planticola bacteremia.
AB  - PURPOSE: Numerous case reports regarding Raoultella planticola infection have
      accumulated in the literature; however, its significance as a clinical pathogen
      remains unknown. We performed a retrospective review of R. planticola bacteremia
      to characterize its clinical features, antimicrobial susceptibility, and patient
      outcome. METHODS: Raoultella planticola bacteremia cases were culled from an
      electronic database of all bacteremia cases occurring over a 4-year-period.
      Medical records were retrospectively reviewed and demographic data, clinical
      findings, presence of underlying disease, results of antimicrobial susceptibility
      testing, and the antibiotic regimens administered during the treatment were
      evaluated. RESULTS: Raoultella planticola was isolated from blood culture
      specimens in 20 cases. The majority of these patients had underlying malignant
      conditions (17 patients, 85%). The most prevalent causes of malignancy were
      adenocarcinoma involving the gallbladder or bile duct (7 patients) and
      hematologic malignancies (6 patients). No cases with resistance to carbapenem or
      third generation cephalosporins were found. All 14 patients with R. planticola as
      the sole microbial isolate recovered with the use of empirical antibiotics. Of
      the six patients with polymicrobial infection, three did not recover and
      subsequently expired. CONCLUSIONS: Raoultella planticola bacteremia seemed to
      occur mainly in immunocompromised patients, and was also frequently found in
      patients with lesions involving the gallbladder or bile duct. The overall outcome
      was favorable when R. planticola was treated with administration of empirical
      antibiotics. Mixed outcomes were found when blood cultures yielded multiple
      species of microbes.

PMID- 25047269
TI  - Menopause status as the main factor explaining the gender differences of serum
      nitric oxide concentrations in middle-aged population.
AB  - PURPOSE: The aim of this study was to investigate whether the observed
      differences between serum NOx levels of men and women were influenced by the
      menopausal status of women. METHODS: A total of 1,209 eligible subjects, aged 40
      60 years, were recruited from among participants of the Tehran lipid and glucose
      study, and subdivided into three groups: men (n = 457), women with regular cycles
      (n = 288) and postmenopausal women (n = 464). Serum concentrations of NOx were
      compared between these groups using Kruskal Wallis-Mann-Whitney U test, followed
      by Bonferroni correction. ANCOVA was applied for comparison of log-transformed
      NOx values between groups after adjustment for confounder variables. RESULTS: The
      mean (SD) of age and BMI did not differ between studied groups. There were
      statistically significant differences between the medians (inter-quartile ranges)
      of serum NOx levels in men, women with regular cycles and the postmenopausal
      women [26 (20-37), 25.5 (19-39) and 29 (21-43) MUmol/L], respectively (P =
      0.012). Post hoc pair-wised comparison, adjusted with Bonferroni correction,
      demonstrated that women with postmenopausal status had higher serum levels of NOx
      values than those women with regular cycle or men (P = 0.011). The results
      remained unchanged after further adjustment for potential confounders.
      CONCLUSION: These results provide evidence that differences observed between
      serum NOx values of middle-aged women and men are more related to menopausal
      status rather than gender.

PMID- 25047270
TI  - Leiomyomas beyond the uterus; benign metastasizing leiomyomatosis with paraaortic
      metastasizing endometriosis and intravenous leiomyomatosis: a case series and
      review of the literature.
AB  - Uterine leiomyomas affect 20-30 % of women 35 years and older. Extrauterine
      leiomyomas are rare and present a greater diagnostic challenge. Those unusual
      growth patterns occur more often in women of reproductive age with a history of
      hysterectomy or surgery for uterine leiomyomas. They have been reported in the
      literature in case reports and small case series and include benign metastasizing
      leiomyoma (BML), disseminated peritoneal leiomyomatosis, intravenous
      leiomyomatosis (IVL), parasitic leiomyomas, and retroperitoneal growth. In this
      case series we present a case of BML with a first report of concomitant
      endometriosis metastasis to paraaortic lymphnodes, and a case of IVL. The
      findings and surgical management of those cases, as well as a review of the
      literature pertinent to those entities, are also presented. 

PMID- 25047271
TI  - Bioelectrical impedance analysis in the assessment of pre-eclampsia.
AB  - PURPOSE: Aim of this prospective investigation was to assess pre-eclampsia by
      bioelectrical impedance analysis (BIA). METHODS: A total of 22 pre-eclamptic as
      well as matched (patients' age, gestational age, parity, gravidity) healthy
      pregnant women underwent whole body BIA on admission and then, pre-eclamptic
      patients, every 2 days until childbirth. For all measured BIA single values and
      their corresponding reference value mean, standard deviation, minimum and maximum
      were calculated to compare pre-eclamptic women with corresponding reference
      values. Furthermore a paired t test and an ANOVA of repeated measurements were
      performed to detect differences of intraindividual measurements. Subsequently an
      analysis of variance was accomplished to analyse general changes in the course of
      time of investigated patients, who were measured more than once. RESULTS: Except
      for the phase angle, BIA parameters of pre-eclamptic women compared to
      corresponding reference values were significantly different, suggesting an
      increase of total body water in pre-eclampsia. Repeated measurements did not
      reveal statistically significant intra- or interindividual differences in the
      course of time. CONCLUSION: Bioelectrical impedance analysis allows
      differentiating healthy from pre-eclamptic women. Further investigations are
      needed to analyse if BIA is capable to serve as a prognostic diagnostic tool in
      the detection of deterioration of pre-eclampsia.

PMID- 25047272
TI  - Detection of the pan neuronal marker PGP9.5 by immuno-histochemistry and
      quantitative PCR in eutopic endometrium from women with and without
      endometriosis.
AB  - PURPOSE: To assess endometrial gene as well as protein expression of
      neuroendocrine and supposedly endometriosis-associated product PGP9.5 and pain
      symptoms in women with endometriosis and controls undergoing laparoscopy, using
      molecular biological and immuno-histochemical approaches in the same patients.
      METHODS: Biopsy of eutopic endometrium from 29 patients by sharp curettage, and
      preparation of paraffin blocks. Determination of PGP9.5 gene expression and
      protein abundance using qPCR and immuno-histochemistry. RESULTS: qPCR; The PGP9.5
      mRNA expression level between women with (N = 16) and without (N = 13)
      endometriosis was not different, regardless of pain symptoms or menstrual cycle
      phase. PGP9.5 expression was higher in women who reported pain compared to those
      who did not; however, this association was not statistically significant. The
      expression of PGP9.5 mRNA was higher in women with endometriosis and pain during
      the proliferative than in the secretory phase (P = 0.03). Furthermore, in the
      first half of the cycle, the abundance of the PGP9.5 transcript was also
      significantly higher in endometriosis patients compared to those without (P =
      0.03). Immuno-histochemistry; Thirteen of the 16 endometriosis patients showed
      positive PGP9.5 immuno-reactivity in the endometrium, whereas no such signal was
      observed in women without endometriosis. The absolute number of nerve fibres per
      mm(2) in women with endometriosis was similar, regardless of the pain symptoms.
      CONCLUSIONS: PGP9.5 mRNA expression is increased in the proliferative phase of
      endometriotic women with pain. The presence of nerve fibres was demonstrated by a
      PGP9.5 protein signal in immuno-histochemistry and restricted to patients with
      endometriosis. Based on these results, however, there did not appear to be a
      direct association between the gene expression and protein abundance in women
      with and without endometriosis or those that experienced pain.

PMID- 25047273
TI  - Retrospective evaluation of borderline ovarian tumors: single center experience
      of 183 cases.
AB  - PURPOSE: Borderline ovarian tumors (BOTs) constitute about a quarter of
      epithelial ovarian malignancies and require different treatment approaches. The
      present study aims to document the experience of a single center on the treatment
      outcome of women who had conservative or comprehensive surgery for BOTs. METHODS:
      One hundred eighty-three patients with BOTs, diagnosed and/or treated in our
      center between January of 2000 and March of 2013, were reviewed retrospectively.
      RESULTS: The mean age at diagnosis was 40.6 years old (range 17-78). Ninety-five
      patients (51 %) were <=40 years. Comprehensive surgical staging and fertility
      sparing surgery were performed in 49 % (n = 91) and 48 % of patients (n = 89)
      respectively. A hundred and forty-seven patients had stage IA disease (80 %). The
      most common type of BOT was serous in histology with 18 % bilateralism. CA-125
      and CA-199 levels were increased in 29 (19 %) and 15 (10 %) patients with stage
      IA disease. Non-invasive tumor implants were diagnosed in 9 patients (4 %) and
      uterine involvement was 2 % among BOT patients that underwent hysterectomies. The
      mean post-operative follow-up period was 20.4 months (range 6-78 months). Disease
      recurrence was seen in 5 patients indicating overall recurrence rate of 2.7 %.
      CONCLUSIONS: In our study, we evaluated a large data pool of 183 patients
      diagnosed with borderline epithelial ovarian tumors. BOTs have a relatively
      better prognosis than invasive epithelial ovarian cancer. Surgery with proper
      staging is the cornerstone of treatment. Patients with BOTs at the early stage
      can undergo fertility sparing surgery with close follow-up.

PMID- 25047274
TI  - Expedient metrics to describe plant community change across gradients of
      anthropogenic influence.
AB  - Human influence associated with land use may cause considerable biodiversity
      losses, namely in oceanic islands such as the Azores. Our goal was to identify
      plant indicator species across two gradients of increasing anthropogenic
      influence and management (arborescent and herbaceous communities) and determine
      similarity between plant communities of uncategorized vegetation plots to those
      in reference gradients using metrics derived from R programming. We intend to
      test and provide an expedient way to determine the conservation value of a given
      uncategorized vegetation plot based on the number of native, endemic, introduced,
      and invasive indicator species present. Using the metric IndVal, plant taxa with
      a significant indicator value for each community type in the two anthropogenic
      gradients were determined. A new metric, ComVal, was developed to assess the
      similarity of an uncategorized vegetation plot toward a reference community type,
      based on (i) the percentage of pre-defined indicator species from reference
      communities present in the vegetation plots, and (ii) the percentage of indicator
      species, specific to a given reference community type, present in the vegetation
      plot. Using a data resampling approach, the communities were randomly used as
      training or validation sets to classify vegetation plots based on ComVal. The
      percentage match with reference community types ranged from 77 to 100 % and from
      79 to 100 %, for herbaceous and arborescent vegetation plots, respectively. Both
      IndVal and ComVal are part of a suite of useful tools characterizing plant
      communities and plant community change along gradients of anthropogenic influence
      without a priori knowledge of their biology and ecology.

PMID- 25047275
TI  - Climate change mitigation and adaptation in the land use sector: from
      complementarity to synergy.
AB  - Currently, mitigation and adaptation measures are handled separately, due to
      differences in priorities for the measures and segregated planning and
      implementation policies at international and national levels. There is a growing
      argument that synergistic approaches to adaptation and mitigation could bring
      substantial benefits at multiple scales in the land use sector. Nonetheless,
      efforts to implement synergies between adaptation and mitigation measures are
      rare due to the weak conceptual framing of the approach and constraining policy
      issues. In this paper, we explore the attributes of synergy and the necessary
      enabling conditions and discuss, as an example, experience with the Ngitili
      system in Tanzania that serves both adaptation and mitigation functions. An in
      depth look into the current practices suggests that more emphasis is laid on
      complementarity-i.e., mitigation projects providing adaptation co-benefits and
      vice versa rather than on synergy. Unlike complementarity, synergy should
      emphasize functionally sustainable landscape systems in which adaptation and
      mitigation are optimized as part of multiple functions. We argue that the current
      practice of seeking co-benefits (complementarity) is a necessary but insufficient
      step toward addressing synergy. Moving forward from complementarity will require
      a paradigm shift from current compartmentalization between mitigation and
      adaptation to systems thinking at landscape scale. However, enabling policy,
      institutional, and investment conditions need to be developed at global,
      national, and local levels to achieve synergistic goals. 

PMID- 25047277
TI  - Identification of selective agonists and positive allosteric modulators for u-
      and delta-opioid receptors from a single high-throughput screen.
AB  - Hetero-oligomeric complexes of G protein-coupled receptors (GPCRs) may represent
      novel therapeutic targets exhibiting different pharmacology and tissue- or cell
      specific site of action compared with receptor monomers or homo-oligomers. An
      ideal tool for validating this concept pharmacologically would be a hetero
      oligomer selective ligand. We set out to develop and execute a 1536-well high
      throughput screen of over 1 million compounds to detect potential hetero-oligomer
      selective ligands using a beta-arrestin recruitment assay in U2OS cells
      coexpressing recombinant u- and delta-opioid receptors. Hetero-oligomer selective
      ligands may bind to orthosteric or allosteric sites, and we might anticipate that
      the formation of hetero-oligomers may provide novel allosteric binding pockets
      for ligand binding. Therefore, our goal was to execute the screen in such a way
      as to identify positive allosteric modulators (PAMs) as well as agonists for u,
      delta, and hetero-oligomeric receptors. While no hetero-oligomer selective
      ligands were identified (based on our selection criteria), this single screen did
      identify numerous u- and delta-selective agonists and PAMs as well as
      nonselective agonists and PAMs. To our knowledge, these are the first u- and
      delta-opioid receptor PAMs described in the literature. 

PMID- 25047279
TI  - Dynamic variability of the heading-flowering stages of single rice in China based
      on field observations and NDVI estimations.
AB  - Although many studies have indicated the consistent impact of warming on the
      natural ecosystem (e.g., an early flowering and prolonged growing period), our
      knowledge of the impacts on agricultural systems is still poorly understood. In
      this study, spatiotemporal variability of the heading-flowering stages of single
      rice was detected and compared at three different scales using field-based
      methods (FBMs) and satellite-based methods (SBMs). The heading-flowering stages
      from 2000 to 2009 with a spatial resolution of 1 km were extracted from the
      SPOT/VGT NDVI time series data using the Savizky-Golay filtering method in the
      areas in China dominated by single rice of Northeast China (NE), the middle-lower
      Yangtze River Valley (YZ), the Sichuan Basin (SC), and the Yunnan-Guizhou Plateau
      (YG). We found that approximately 52.6 and 76.3 % of the estimated heading
      flowering stages by a SBM were within +/-5 and +/-10 days estimation error (a
      root mean square error (RMSE) of 8.76 days) when compared with those determined
      by a FBM. Both the FBM data and the SBM data had indicated a similar spatial
      pattern, with the earliest annual average heading-flowering stages in SC,
      followed by YG, NE, and YZ, which were inconsistent with the patterns reported in
      natural ecosystems. Moreover, diverse temporal trends were also detected in the
      four regions due to different climate conditions and agronomic factors such as
      cultivar shifts. Nevertheless, there were no significant differences (p > 0.05)
      between the FBM and the SBM in both the regional average value of the
      phenological stages and the trends, implying the consistency and rationality of
      the SBM at three scales.

PMID- 25047280
TI  - Patient and professional attitudes towards research in general practice: the RepR
      qualitative study.
AB  - BACKGROUND: Since the 1990s, professional institutions worldwide have emphasised
      the need to develop research in general practice to improve the health of the
      population. The recent creation of professorships in general practice in French
      Universities should foster research in this field. Our aim was to explore the
      views of patients and relevant professionals on research in general practice.
      METHODS: Qualitative study, using the grounded theory approach according to
      Strauss and Corbin, conducted in 2010 in three French regions. Nine focus groups
      were run to data saturation, and included 57 participants in four different
      categories: patients, non-academic GPs, academic GPs, academics in other
      disciplines. RESULTS: Most of the participants in the four categories described
      research in general practice as specific to the population managed and relevant
      for health care. They considered that its grounding in day-to-day practice
      enabled pragmatic approaches. The influence of the pharmaceutical industry,
      rivalries between university disciplines and a possible gap between research and
      practice were considered as pitfalls. The barriers identified were
      representations of the medical researcher as a "laboratory worker", the lack of
      awareness of any research in the discipline, and lack of time and training. While
      the views of patients and non-academic GPs are mostly focused on professional
      issues and the views of academics other than GPs on technical issues, academic
      GPs are in a position to play a role of interface between the universities and
      general practices. CONCLUSIONS: Although the role of GPs in research is perceived
      differently by the various protagonists, research in general practice has an
      undisputed legitimacy in France. Solutions for overcoming the identified barriers
      include research networks with appropriate resources and training and
      scientifically sound collaborative research projects, as already implemented in
      leading countries.

PMID- 25047281
TI  - Pacemaker endocarditis caused by Propionibacterium acnes in an adult patient with
      Ebstein's anomaly: a report of a rare case.
AB  - We report a rare case of a Brazilian adult woman with Ebstein's Anomaly who
      presented with pacemaker endocarditis caused by Propionibacterium acnes.
      Ebstein's Anomaly is a rare congenital malformation of the heart. Infective
      endocarditis is defined as an infection of heart valves, of the mural
      endocardium, of a septal defect, or of a cardiac electronic implantable device.
      Propionibacterium acnes is a skin commensal bacterium, that is usually considered
      as a contaminant, but can, on rare occasions, cause serious infections including
      endocarditis of prosthetic valves, native valves and cardiac electronic
      implantable devices. Diagnosis was made after nearly two years of investigation
      by identification of the organism by the MALDI-TOF technique and transoesophageal
      echocardiogram. The patient was successfully treated with daptomycin and device
      removal. She remains free of endocarditis after 32 months of follow-up. 

PMID- 25047282
TI  - Hydrogen sulfide inhibits human platelet aggregation in vitro in part by
      interfering gap junction channels: effects of ACS14, a hydrogen sulfide-releasing
      aspirin.
AB  - BACKGROUND: Hydrogen sulfide (H2S), as a newly identified gaseous mediator, has
      been widely investigated in various systems. However, the effect of H2S on
      cardiovascular system haemostasis, including platelet aggregation and the precise
      mechanisms remain unclear. Therefore, the present study was aimed to examine the
      inhibitory effect of H2S on human platelet aggregation in vitro and its relevance
      to gap junction channels. METHODS AND RESULTS: The antiaggregatory property of
      H2S-releasing aspirin derivative (ACS14) was compared with its mother compound,
      aspirin. In comparison to an equimolar dose of aspirin, ACS14 not only exerted a
      more potent inhibitory effect on platelet aggregation induced by ADP or thrombin,
      but also significantly inhibited alphaIIbbeta3 integrin activation and P-selectin
      expression. Similarly, NaHS (100MUM), a conventional H2S donor significantly
      inhibited platelet aggregation as well as alphaIIbbeta3 integrin activation and P
      selectin expression induced by ADP or thrombin. Furthermore, pretreatment with
      rotigaptide, a gap junction modifier abolished the inhibitory properties of ACS14
      or NaHS on platelet aggregation, suggesting that suppression of platelet
      aggregation by H2S is, at least in part, gap junction channel-dependent.
      CONCLUSIONS: H2S may inhibit human platelet aggregation at least in part by
      depressing gap junction intercellular communication and H2S released from ACS14
      may contribute to its additional anti-platelet effect in vitro in comparison to
      aspirin.

PMID- 25047284
TI  - The legacy of Nicki R. Crick's contributions to developmental psychopathology.

PMID- 25047283
TI  - The freestyle aortic bioprosthesis: a systematic review.
AB  - BACKGROUND: The Medtronic Freestyle bioprosthesis (FSB) provides an alternative
      to other prostheses for both aortic valve and aortic root surgery. This paper is
      a systematic review of the post-operative outcomes in patients with aortic valve
      and/or aortic root disease following FSB implantation. METHODS: Electronic
      databases were searched for primary analysis, prospective randomised studies
      comparing the FSB with an alternative aortic prosthesis were included.
      Additionally, case series that included data for at least 100 individual operated
      patients were used for secondary analysis. RESULTS: Among three identified
      randomised studies, 199 FSB cases were compared with homografts, and stented and
      an alternative stentless bioprosthesis. The FSB showed comparable hospital
      mortality (4.5% vs. 5.3%) and eight-year actuarial survival (80+/-5.0% versus
      77+/-6.0%) with the homograft (respectively) and comparable reduction in left
      ventricular mass index relative to other prosthesis types. Over 6000 individual
      patients were included in the selected 15 case series. Weighted mean operative
      mortality, neurological event rate and five-year actuarial survival was 5.2%,
      5.5% and 77.8%, respectively. CONCLUSION: The FSB performed comparably against
      alternative prostheses regarding in-hospital mortality, long-term survival and
      reduction in left ventricular mass index. Included case series demonstrated
      robust post-operative outcomes in both the short and long term.

PMID- 25047285
TI  - A gender-balanced approach to the study of peer victimization and aggression
      subtypes in early childhood.
AB  - A short-term longitudinal study during early childhood (N = 301; 155 girls; M =
      44.76 months old, SD = 8.20) investigated the prospective associations between
      peer victimization and aggression subtypes. Specifically, observations of
      relational and physical victimization as well as teacher reports of the forms
      (i.e., relational and physical) and functions (i.e., proactive and reactive) of
      aggression were collected at two time points during an academic year. Within- and
      between-group gender differences were examined as part of the preliminary
      analyses. In order to address key study questions, both directions of effect
      between peer victimization and aggression subtypes were examined. We found that
      teacher-reported proactive relational aggression predicted decreases in observed
      relational victimization over time, whereas reactive relational aggression
      predicted increases in observed relational victimization over time. Ways in which
      these and other findings extend the literature are discussed. 

PMID- 25047286
TI  - Physiological stress reactivity and physical and relational aggression: the
      moderating roles of victimization, type of stressor, and child gender.
AB  - The purpose of the present investigation was to examine the association between
      physiological reactivity to peer stressors and physical and relational
      aggression. Potential moderation by actual experiences of peer maltreatment
      (i.e., physical and relational victimization) and gender were also explored. One
      hundred ninety-six children (M = 10.11 years, SD = 0.64) participated in a
      laboratory stress protocol during which their systolic blood pressure, diastolic
      blood pressure, and skin conductance reactivity to recounting a relational
      stressor (e.g., threats to relationships) and an instrumental stressor (e.g.,
      threats to physical well-being, dominance, or property) were assessed. Teachers
      provided reports of aggression and victimization. In both boys and girls,
      physical aggression was associated with blunted physiological reactivity to
      relational stress and heightened physiological reactivity to instrumental stress,
      particularly among youth higher in victimization. In girls, relational aggression
      was most robustly associated with blunted physiological reactivity to relational
      stressors, particularly among girls exhibiting higher levels of relational
      victimization. In boys, relational aggression was associated with heightened
      physiological reactivity to both types of stressors at higher levels of peer
      victimization and blunted physiological reactivity to both types of stressors at
      lower levels of victimization. Results underscore the shared and distinct
      emotional processes underlying physical and relational aggression in boys and
      girls. 

PMID- 25047288
TI  - Mechanisms and processes of relational and physical victimization, depressive
      symptoms, and children's relational-interdependent self-construals: implications
      for peer relationships and psychopathology.
AB  - This short-term longitudinal study examined the associations between relational
      and physical victimization and depressive symptoms, and the moderating role of
      school-aged children's relational-interdependent self-construals in these
      associations. The participants were 387 children (51.8% boys) who were in the
      fifth grade (M = 10.48 years, SD = 0.55) in Taiwan and followed at two time
      points (a 6-month interval) during a calendar year. A multiple-informant approach
      was used where forms of peer victimization, depressive symptoms, and relational
      interdependent self-construals were assessed via peer nominations, teacher
      reports, and child reports, respectively. All measures had favorable psychometric
      properties. The results of a multigroup cross-lagged model demonstrated that
      relational victimization (not physical victimization) was positively predictive
      of subsequent depressive symptoms, and the effect was evidenced for highly
      interdependent children only. The opposite link was also significant, such that
      depressive symptoms predicted subsequent relational victimization (not physical
      victimization) for children who exhibited low and high levels of relational
      interdependent self-construals. In contrast, physical victimization predated a
      lower level of depressive symptoms for highly interdependent children. These
      effects were unaffected by the gender of the child. The findings, especially the
      interactive effects of relational victimization (as a contextual factor) and
      relational-interdependent self-construals (as an individual vulnerability) on
      depressive symptoms, are discussed from a developmental psychopathology
      perspective. 

PMID- 25047287
TI  - Relational victimization, friendship, and adolescents' hypothalamic-pituitary
      adrenal axis responses to an in vivo social stressor.
AB  - Adolescents' peer experiences may have significant associations with biological
      stress-response systems, adding to or reducing allostatic load. This study
      examined relational victimization as a unique contributor to reactive
      hypothalamic-pituitary-adrenal (HPA) axis responses as well as friendship quality
      and behavior as factors that may promote HPA recovery following a stressor. A
      total of 62 adolescents (ages 12-16; 73% female) presenting with a wide range of
      life stressors and adjustment difficulties completed survey measures of peer
      victimization and friendship quality. Cortisol samples were collected before and
      after a lab-based interpersonally themed social stressor task to provide measures
      of HPA baseline, reactivity, and recovery. Following the stressor task,
      adolescents discussed their performance with a close friend; observational coding
      yielded measures of friends' responsiveness. Adolescents also reported positive
      and negative friendship qualities. Results suggested that higher levels of
      adolescents' relational victimization were associated with blunted cortisol
      reactivity, even after controlling for physical forms of victimization and other
      known predictors of HPA functioning (i.e., life stress or depressive symptoms).
      Friendship qualities (i.e., low negative qualities) and specific friendship
      behaviors (i.e., high levels of responsiveness) contributed to greater HPA
      regulation; however, consistent with theories of rumination, high friend
      responsiveness in the context of high levels of positive friendship quality
      contributed to less cortisol recovery. Findings extend prior work on the
      importance of relational victimization and dyadic peer relations as unique and
      salient correlates of adaptation in adolescence. 

PMID- 25047289
TI  - Aggression, hostile attributions, status, and gender: a continued quest.
AB  - This study had two goals. The first goal was to examine the association between
      two indicators of negative bias in children and their associations with
      children's aggression. The second goal was to examine a possible dual role of
      social status, operationalized as popularity, as a concurrent correlate of
      negative bias and as a moderator of the effect of negative bias on children's
      aggression. The roles of gender and type of aggression were also examined.
      Participants were 366 fifth- and sixth-grade children (49% girls; M age = 11.07
      years, SD = 0.85 year) who completed peer- and self-report measures in their
      classrooms. The results showed that the two indicators of negative bias were
      associated with each other and with children's aggression. Popularity was weakly
      associated with negative bias. However, popularity did moderate the association
      of hostile attributions with aggression. The associations of both measures of
      negative bias with aggression also varied by gender, with stronger associations
      for boys than for girls. Theoretical and practical implications are discussed. 

PMID- 25047290
TI  - Heightened emotional sensitivity intensifies associations between relational
      aggression and victimization among girls but not boys: a longitudinal study.
AB  - Founded in the social process model, the aim of this study was to identify
      whether the associations of relational aggression with concurrent and subsequent
      relational victimization differed depending on early adolescents' personal
      vulnerabilities and gender. The vulnerabilities of interest were social
      information processing variables that convey greater emotional sensitivity,
      including rejection sensitivity, fear of negative evaluation, and avoidance of
      intimacy. Participants were 358 early adolescents (176 boys, 178 girls) aged 9 to
      13 years. Relational aggression and victimization were assessed via peer
      nominations, whereas the three indicators of emotional sensitivity were assessed
      via self-report. Overall, results revealed greater relational aggression at Time
      1 to be associated with greater relational victimization at both Time 1 and Time
      2. However, this finding was qualified by both emotional sensitivity and gender.
      When considered separately, girls who were relationally aggressive and
      emotionally sensitive were at increased risk of victimization at both assessment
      points. In contrast, no link was found between relational aggression and
      victimization for boys, although relational vulnerabilities did have unique
      associations with boys' relational victimization. These findings have
      implications for our understanding of relational aggression and victimization, as
      well as for the development of interventions aimed at reducing these problems. 

PMID- 25047292
TI  - Why the bully/victim relationship is so pernicious: a gendered perspective on
      power and animosity among bullies and their victims.
AB  - The bully/victim relationship was studied in a sample of elementary school
      children (N = 1,289 in first, third, and fifth grades). Three questions were
      tested. Does bullying involve a power differential between bully and victim? Are
      bully/victim dyads participants in a relationship, whether mutual liking or
      disliking? Does the gender composition of the bully/victim dyad moderate power
      differential and relational context patterns? Hierarchical linear modeling was
      used to analyze predictors of the reputational strength of bully/victim ties. The
      findings revealed that the bully/victim dyads most frequently nominated by peers
      were characterized by asymmetries in social status, where bullies were
      increasingly more popular than their victims, and by asymmetries in aggression,
      where bullies were increasingly less aggressive than their victims. Bullies and
      victims were likely to select one another as among the children that they least
      like. Most effects with respect to aggression, popularity, and relationships were
      moderated by the gender composition of the bully/victim dyad. Implications for a
      developmental psychopathology perspective on peer bullying and victimization are
      highlighted. 

PMID- 25047291
TI  - It gets better or does it? Peer victimization and internalizing problems in the
      transition to young adulthood.
AB  - Consistent research shows that peer victimization predicts internalizing symptoms
      in childhood and adolescence, but the extent to which peer victimization and its
      harmful effects on mental health persists into young adulthood is unclear. The
      current study describes patterns of physical and relational victimization during
      and after high school, and examines concurrent and prospective associations
      between internalizing symptoms (depressive and anxious symptoms) and peer
      victimization (physical and relational) from adolescence to young adulthood (ages
      12-27). Data were collected from the Victoria Healthy Youth Survey, a five-wave
      multicohort study conducted biennially between 2003 and 2011 (N = 662). Physical
      victimization was consistently low and stable over time. Relational victimization
      increased for males after high school. Both types of victimization were
      associated concurrently with internalizing symptoms across young adulthood for
      males and for females. Although sex differences were important, victimization in
      high school also predicted increases in internalizing problems over time. 

PMID- 25047293
TI  - Profiles of the forms and functions of self-reported aggression in three
      adolescent samples.
AB  - In the current study, we addressed several issues related to the forms (physical
      and relational) and functions (reactive and proactive) of aggression in community
      (n = 307), voluntary residential (n = 1,917), and involuntarily detained (n =
      659) adolescents (ages 11-19 years). Across samples, boys self-reported more
      physical aggression and girls reported more relational aggression, with the
      exception of higher levels of both forms of aggression in detained girls.
      Further, few boys showed high rates of relational aggression without also showing
      high rates of physical aggression. In contrast, it was not uncommon for girls to
      show high rates of relational aggression alone, and these girls tended to also
      have high levels of problem behavior (e.g., delinquency) and mental health
      problems (e.g., emotional dysregulation and callous-unemotional traits). Finally,
      for physical aggression in both boys and girls, and for relational aggression in
      girls, there was a clear pattern of aggressive behavior that emerged from cluster
      analyses across samples. Two aggression clusters emerged, with one group showing
      moderately high reactive aggression and a second group showing both high reactive
      and high proactive aggression (combined group). On measures of severity (e.g.,
      self-reported delinquency and arrests) and etiologically important variables
      (e.g., emotional regulation and callous-unemotional traits), the reactive
      aggression group was more severe than a nonaggressive cluster but less severe
      than the combined aggressive cluster. 

PMID- 25047295
TI  - Dwelling on it may make it worse: the links between relational victimization,
      relational aggression, rumination, and depressive symptoms in adolescents.
AB  - Although there is considerable evidence that relational victimization is
      associated with depressive symptoms in youth, our understanding about the
      mechanisms by which victimization and depressive symptoms are linked is limited.
      The current study explored ruminating about victimization experiences as a
      potential mechanism that might contribute to an understanding of the association
      between relational victimization and depressive symptoms. We also tested the
      specificity of the proposed models by controlling for and testing parallel models
      of a highly related behavior: relational aggression. A sample of 499 adolescents
      from sixth through eighth grades participated. Teacher reports were used to
      assess relational victimization and relational aggression. Self-reports were used
      to assess depressive symptoms and rumination. The results showed that rumination
      partially mediated the association between relational victimization and
      depressive symptoms. No moderation effect was found. In contrast, rumination
      moderated the association between relational aggression and depressive symptoms.
      Specifically, relational aggression was associated with depressive symptoms for
      those adolescents who were also ruminators. Thus, ruminating about victimization
      experiences appears to be an important mechanism that functions differently for
      relational aggression and relational victimization in conferring risk for
      depressive symptoms. The findings offer important practical implications for
      those working with adolescents and also lay the groundwork for future research. 

PMID- 25047294
TI  - Moving against and away from the world: the adolescent legacy of peer
      victimization.
AB  - Nicki Crick initiated a generative line of theory and research aimed at exploring
      the implications of exposure to overt and relational aggression for youth
      development. The present study aimed to continue and expand this research by
      examining whether early (second grade) and increasing (second-sixth grade) levels
      of victimization during elementary school contributed to youths' tendencies to
      move against, away from, or toward the world of peers following the transition to
      middle school. Youth (M age in second grade = 7.96 years, SD = 0.35; 338 girls,
      298 boys) reported on their exposure to victimization and their social goals
      (performance-approach, performance-avoidance, or mastery). Teachers reported on
      youths' exposure to victimization and their engagement in antisocial, socially
      helpless, and prosocial behavior. Latent growth curve analyses revealed that
      early and increasing levels of both overt and relational victimization uniquely
      contributed to multifinality in adverse developmental outcomes, predicting all
      three social orientations (high conflictual engagement, high disengagement, and
      low positive engagement). The pattern of effects was robust across sex and after
      adjusting for youths' early social motivation. These findings confirm that both
      forms of victimization leave an enduring legacy on youths' social health in
      adolescence. Given that profiles of moving against and away from the world can
      contribute to subsequent psychopathology, understanding and preventing this
      legacy is pivotal for developing effective intervention programs aimed at
      minimizing the effects of peer adversity. 

PMID- 25047296
TI  - Relational aggression and psychological control in the sibling relationship:
      mediators of the association between maternal psychological control and
      adolescents' emotional adjustment.
AB  - The association between mothers' psychological control and their children's
      emotional adjustment problems is well documented. However, processes that may
      explain this association are not well understood. The present study tested the
      idea that relational aggression and psychological control within the context of
      the sibling relationship may help to account for the relation between mothers'
      psychological control and adolescents' internalizing symptoms. Older (M = 16.46,
      SD = 1.35 years) and younger (M = 13.67, SD = 1.56 years) siblings from 101 dyads
      rated the psychological control they received from mothers and siblings, and the
      relational aggression they received from siblings. Despite some similarities
      between psychological control and relational aggression, confirmatory factor
      analyses provided evidence that the two sibling processes are distinct. Maternal
      psychological control was related to psychological control and relational
      aggression within the sibling relationship, which were related to adolescents'
      anxiety and depressed mood. In addition, sibling relational aggression was a more
      powerful mediator of the relationship between maternal psychological control and
      adolescent adjustment than sibling psychological control. 

PMID- 25047298
TI  - Parenting, relational aggression, and borderline personality features:
      associations over time in a Russian longitudinal sample.
AB  - Crick, Murray-Close, and Woods (2005) encouraged the study of relational
      aggression as a developmental precursor to borderline personality features in
      children and adolescents. A longitudinal study is needed to more fully explore
      this association, to contrast potential associations with physical aggression,
      and to assess generalizability across various cultural contexts. In addition,
      parenting is of particular interest in the prediction of aggression or borderline
      personality disorder. Early aggression and parenting experiences may differ in
      their long-term prediction of aggression or borderline features, which may have
      important implications for early intervention. The currrent study incorporated a
      longitudinal sample of preschool children (84 boys, 84 girls) living in intact,
      two-parent biological households in Voronezh, Russia. Teachers provided ratings
      of children's relational and physical aggression in preschool. Mothers and
      fathers also self-reported their engagement in authoritative, authoritarian,
      permissive, and psychological controlling forms of parenting with their
      preschooler. A decade later, 70.8% of the original child participants consented
      to a follow-up study in which they completed self-reports of relational and
      physical aggression and borderline personality features. The multivariate results
      of this study showed that preschool relational aggression in girls predicted
      adolescent relational aggression. Preschool aversive parenting (i.e.,
      authoritarian, permissive, and psychologically controlling forms) significantly
      predicted aggression and borderline features in adolescent females. For
      adolescent males, preschool authoritative parenting served as a protective factor
      against aggression and borderline features, whereas authoritarian parenting was a
      risk factor for later aggression. 

PMID- 25047297
TI  - Social cognitions, distress, and leadership self-efficacy: associations with
      aggression for high-risk minority youth.
AB  - Urban ethnic minority youth are often exposed to high levels of aggression and
      violence. As such, many aggression intervention programs that have been designed
      with suburban nonethnic minority youth have been used or slightly adapted in
      order to try and meet the needs of high-risk urban youth. The current study
      contributes to the literature base by examining how well a range of social
      cognitive, emotional distress and victimization, and prosocial factors are
      related to youth aggression in a sample of urban youth. This study utilized data
      gathered from 109 9- to 15-year-old youth (36.7% male; 84.4% African American)
      and their parents or caregivers. A series of hierarchical multiple regressions
      were fit predicting youth aggression from social-cognitive variables,
      victimization and distress, and prosocial variables, controlling for youth gender
      and age. Each set of variables explained a significant and unique amount of the
      variance in youth aggressive behavior. The full model including all predictors
      accounted for 41% of the variance in aggression. Models suggest that youth with
      stronger beliefs supportive of violence, youth who experience more overt
      victimization, and youth who experience greater distress in overtly aggressive
      situations are likely to be more aggressive. In contrast, youth with higher self
      esteem and youth who endorse greater leadership efficacy are likely to be less
      aggressive. Contrary to hypotheses, hostile attributional bias and knowledge of
      social information processing, experience of relational victimization, distress
      in relationally aggressive situations, and community engagement were not
      associated with aggression. Our study is one of the first to address these
      important questions for low-income, predominately ethnic minority urban youth,
      and it has clear implications for adapting aggression prevention programs to be
      culturally sensitive for urban African American youth. 

PMID- 25047299
TI  - Borderline personality features as a predictor of forms and functions of
      aggression during middle childhood: examining the roles of gender and
      physiological reactivity.
AB  - The present longitudinal investigation examined borderline personality features
      as a predictor of aggression 1 year later. Moderation by physiological reactivity
      and gender was also explored. One hundred ninety-six children (M = 10.11 years,
      SD = 0.64) participated in a laboratory stress protocol in which their systolic
      blood pressure, diastolic blood pressure, and skin conductance reactivity to
      recounting a relational stressor (e.g., threats to relationships or exclusion)
      were assessed. Teachers provided reports on subtypes of aggressive behavior
      (i.e., reactive relational, proactive relational, reactive physical, and
      proactive physical), and children completed a self-report measure of borderline
      personality features. Path analyses indicated that borderline personality
      features predicted increases in reactive relational aggression and proactive
      relational aggression among girls who evinced heightened physiological reactivity
      to interpersonal stress. In contrast, borderline personality features predicted
      decreases in proactive physical aggression in girls. Findings suggest that
      borderline personality features promote engagement in relationally aggressive
      behaviors among girls, particularly in the context of emotional dysregulation. 

PMID- 25047301
TI  - Predicting borderline personality disorder symptoms in adolescents from childhood
      physical and relational aggression, depression, and attention
      deficit/hyperactivity disorder.
AB  - Developmental cascade models linking childhood physical and relational aggression
      with symptoms of depression and attention-deficit/hyperactivity disorder (ADHD;
      assessed at ages 10, 11, 12, 13, and 14) to borderline personality disorder (BPD)
      features (assessed at age 14) were examined in a community sample of 484 youth.
      Results indicated that, when controlling for within-time covariance and across
      time stability in the examination of cross-lagged relations among study
      variables, BPD features at age 14 were predicted by childhood relational
      aggression and symptoms of depression for boys, and physical and relational
      aggression, symptoms of depression, and symptoms of ADHD for girls. Moreover, for
      boys BPD features were predicted from age 10 ADHD through age 12 depression,
      whereas for girls the pathway to elevated BPD features at age 14 was from
      depression at age 10 through physical aggression symptoms at age 12. Controlling
      for earlier associations among variables, we found that for girls the strongest
      predictor of BPD features at age 14 was physical aggression, whereas for boys all
      the risk indicators shared a similar predictive impact. This study adds to the
      growing literature showing that physical and relational aggression ought to be
      considered when examining early precursors of BPD features. 

PMID- 25047300
TI  - Borderline personality features in childhood: the role of subtype, developmental
      timing, and chronicity of child maltreatment.
AB  - Child maltreatment has been established as a risk factor for borderline
      personality disorder (BPD), yet few studies consider how maltreatment influences
      the development of BPD features through childhood and adolescence. Subtype,
      developmental timing, and chronicity of child maltreatment were examined as
      factors in the development of borderline personality features in childhood.
      Children (M age = 11.30, SD = 0.94), including 314 maltreated and 285
      nonmaltreated children from comparable low socioeconomic backgrounds, provided
      self-reports of developmentally salient borderline personality traits. Maltreated
      children had higher overall borderline feature scores, had higher scores on each
      individual subscale, and were more likely to be identified as at high risk for
      development of BPD through raised scores on all four subscales. Chronicity of
      maltreatment predicted higher overall borderline feature scores, and patterns of
      onset and recency of maltreatment significantly predicted whether a participant
      would meet criteria for the high-risk group. Implications of findings and
      recommendations for intervention are discussed.

PMID- 25047302
TI  - Moderation of maltreatment effects on childhood borderline personality symptoms
      by gender and oxytocin receptor and FK506 binding protein 5 genes.
AB  - In this investigation, gene-environment-gender interaction effects in predicting
      child borderline personality disorder symptomatology among maltreated and
      nonmaltreated low-income children (N = 1,051) were examined. In the context of a
      summer research camp, adult-, peer-, and self-report assessments of borderline
      precursor indicators were obtained, as well as child self-report on the
      Borderline Personality Features Scale for Children. Genetic variants of the
      oxytocin receptor genotype and the FK506 binding protein 5 gene CATT haplotype
      were investigated. Children who self-reported high levels of borderline
      personality symptomatology were differentiated by adults, peers, and additional
      self-report on indicators of emotional instability, conflictual relationships
      with peers and adults, preoccupied attachment, and indicators of self-harm and
      suicidal ideation. Maltreated children also were more likely to evince many of
      these difficulties relative to nonmaltreated children. A series of analyses of
      covariance, controlling for age and ancestrally informative markers, indicated
      significant Maltreatment * Gene * Gender three-way interactions. Consideration of
      the maltreatment parameters of subtype, onset, and recency expanded understanding
      of variation among maltreated children. The three-way interaction effects
      demonstrated differential patterns among girls and boys. Among girls, the gene
      environment interaction was more consistent with a diathesis-stress model,
      whereas among boys a differential-sensitivity interaction effect was indicated.
      Moreover, the genetic variants associated with greater risk for higher borderline
      symptomatology, dependent on maltreatment experiences, were opposite in girls
      compared to boys. The findings have important implications for understanding
      variability in early predictors of borderline personality pathology. 

PMID- 25047304
TI  - Viewing relational aggression through multiple lenses: temperament, personality,
      and personality pathology.
AB  - Dispositional trait frameworks offer great potential to elucidate the nature and
      development of psychopathology, including the construct of relational aggression.
      The present study sought to explore the dispositional context of relational
      aggression across three dispositional frameworks: temperament, personality, and
      personality pathology. Participants comprised a large community sample of youth,
      aged 6 to 18 years (N = 1,188; 51.2% female). Ratings of children's relational
      aggression, temperament, personality, and personality pathology traits were
      obtained through parent report (86.3% mothers). Results showed convergence and
      divergence across these three dispositional frameworks. Like other antisocial
      behavior subtypes, relational aggression generally showed connections with traits
      reflecting negative emotionality and poor self-regulation. Relational aggression
      showed stronger connections with temperament traits than with personality traits,
      suggesting that temperament frameworks may capture more relationally aggressive
      content. Findings at the lower order trait level help differentiate relational
      aggression from other externalizing problems by providing a more nuanced
      perspective (e.g., both sociability and shyness positively predicted relational
      aggression). In addition, there was little evidence of moderation of these
      associations by gender, age, or age2, and findings remained robust even after
      controlling for physical aggression. Results are discussed in the broader context
      of conceptualizing relational aggression in an overarching personality
      psychopathology framework. 

PMID- 25047303
TI  - Testing an equifinality model of nonsuicidal self-injury among early adolescent
      girls.
AB  - Nonsuicidal self-injury (NSSI) is a common behavior among females that has been
      shown to confer risk for continued self-injury and suicidal attempts. NSSI can be
      viewed conceptually as behavior that is pathognomonic with aggression and/or
      depression. Empirical research on concurrent correlates supports this concept:
      numerous and diverse factors are shown to be significantly associated with self
      harm, including depression, emotion dysregulation, impulsivity, and aggression
      and other conduct problems, as well as environmental stressors such as bullying,
      harsh parenting, and negative life events. In the present study, we test
      hypotheses regarding developmental precursors (measured from ages 8 to 12 years)
      to NSSI in young adolescent girls (ages 13-14 years), specifically whether
      aggression, depression, and environmental stressors distinguish girls with and
      without self-harm, and whether there is evidence for multiple developmental
      pathways to NSSI. Data were derived from the longitudinal Pittsburgh Girls Study.
      In this community sample of girls, the prevalence of NSSI at ages 13 or 14 years
      of age was 6.0%. Initial levels in dimensions measured within the depression,
      aggression, and environmental stressor domains accounted for variance in NSSI in
      early adolescence. Changes over time in relational aggression and assertiveness
      were also significantly associated with risk for NSSI. To a large extent,
      adolescent NSSI was predicted by psychological deficits and stress exposure that
      began early in childhood. Risk indices were calculated using the 85th or 15th
      percentile. Close to 80% of girls who engaged in NSSI during adolescence were
      identified by at least one risk domain in childhood. A sizable proportion of
      adolescent girls who later engaged in NSSI had childhood risk scores in all three
      domains; the remaining girls with adolescent NSSI were relatively evenly
      distributed across the other risk domain profiles. The observation that multiple
      pathways to NSSI exist suggests that deficits underlying the behavior may vary
      and require different modes of prevention. 

PMID- 25047305
TI  - Pharmacokinetic evaluation of intravenous artesunate in adults with uncomplicated
      falciparum malaria in Kenya: a phase II study.
AB  - BACKGROUND: Alternatives to treatment for malaria treatment of travellers are
      needed in the USA and in Europe for travellers who return with severe malaria
      infections. The objective of this study is to show the pharmacokinetic (PK)
      profile of intravenous artesunate (AS), which was manufactured under good
      manufacturing practice (GMP) conditions, in adults with uncomplicated falciparum
      malaria in Kenya. METHODS: The PK parameters of intravenous AS manufactured under
      current cGMP were evaluated after a single dose of drug at 2.4 mg/kg infused over
      2 min in 28 adults with uncomplicated Plasmodium falciparum malaria. Plasma
      concentrations of AS and dihydroartemisinin (DHA) were measured using a validated
      liquid chromatography-mass spectrometry (LC-MS/MS) methodology. Pharmacokinetic
      data were analysed with a compartmental analysis for AS and DHA. RESULTS: The
      results suggest there were no drug-related adverse events in any of the patients.
      After intravenous infusion, the concentration of the parent drug rapidly
      declined, and the AS was converted to DHA. AS and DHA showed mean elimination
      half-lives of 0.17 hours and 1.30 hours, respectively. The high mean peak
      concentration (Cmax) of AS was shown to be 28,558 ng/mL while the Cmax of DHA was
      determined to be 2,932 ng/mL. Significant variability was noted in the PK
      profiles of the 28 patients tested. For example, Cmax values of AS were
      calculated to range from 3,362 to 55,873 ng/mL, and the Cmax value of DHA was
      noted to vary from 1,493 to 5,569 ng/mL. The mean area under the curve (AUC) of
      AS was shown to be approximately half that of DHA (1,878 ng . h/mL vs 3,543 ng .
      h/mL). The DHA/AS ratio observed was 1.94 during the one-day single treatment,
      and the AUC and half- life measured for DHA were significantly larger and longer
      than for AS. CONCLUSIONS: Intravenous AS can provide much higher peak
      concentrations of AS when compared to concentrations achieved with oral therapy;
      this may be crucial for the rapid elimination of parasites in patients with
      severe malaria. Given the much longer half-life of DHA compared to the short half
      life of AS, DHA also plays a significant role in treatment of severe malaria.

PMID- 25047306
TI  - Apathy in late-life depression: common, persistent, and disabling.
AB  - OBJECTIVE: The aims of this study were to examine: (1) the relationship between
      apathy and disability in late-life depression, and (2) the functional
      significance of improvement in apathy following escitalopram treatment in terms
      of its relationship to disability. METHODS: Subjects were 71 non-demented elderly
      with non-psychotic major depression. After a 2-week single-blind placebo period,
      subjects who had Hamilton Depression Rating Scale (HDRS) >= 18 received
      escitalopram 10 mg daily for 12 weeks. Apathy and disability were assessed with
      the Apathy Evaluation Scale (AES) and the World Health Organization Disability
      Assessment Scale II (WHODAS), respectively. These measures and the HDRS were
      administered at baseline and again following 12 weeks of treatment. RESULTS: At
      baseline, 38% of depressed subjects had significant apathy (AES >= 36.5).
      Severity of apathy at baseline significantly correlated with severity of
      disability. In a multivariate regression model, baseline severity of apathy, but
      not the overall depressive syndrome (HDRS), significantly correlated with
      baseline disability. Following escitalopram treatment, improvement in apathy
      significantly correlated with improvement in disability measures, while change in
      the rest of the depressive syndrome did not. The overall change in apathy and
      disability in response to escitalopram treatment was significant but small.
      CONCLUSION: Apathy is common in late-life depression and is associated with
      disability above and beyond the influence of other depressive symptoms. Given the
      strong relationship between apathy and disability, understanding the neurobiology
      of apathy and developing treatments for apathy may improve the functional
      outcomes of late-life depression.

PMID- 25047307
TI  - [International adoption from Ethiopia in a 5-year period].
AB  - INTRODUCTION: An increase in the number of internationally adopted children has
      been observed in the last few years. The country of origin that has experienced a
      greater increase is Ethiopia. The health of internationally adopted children from
      Ethiopia has not been extensively assessed to date. The main objective of the
      study is to determine the prevalence of infectious diseases in children adopted
      from Ethiopia, and to assess their nutritional status. METHOD: A prospective,
      observational cohort study was conducted using the medical records of 251
      children adopted from Ethiopia to Spain in the period from Jan 1, 2006 and
      December 31, 2010. RESULTS: The mean age of the children was 7 months (range 1
      120). Abnormalities were detected on physical examination in 56.6%. In 90% of
      cases the child was less than 5 years-old. Half of the sample had a weight below
      the third percentile, with some degree of malnutrition in 65% of the children.
      HIV exposure was not uncommon (4.8%). CONCLUSIONS: Low weight and acute
      gastroenteritis were the main findings in this cohort. Infectious diseases should
      be systematically assessed.

PMID- 25047308
TI  - Single-incision laparoscopic surgery and conventional laparoscopic treatment of
      varicocele in adolescents: Comparison between two techniques.
AB  - BACKGROUND: Single-incision laparoscopic surgery (SILS) has gained great
      popularity in paediatric surgery due to its minimally invasive approach and
      improved cosmetic results. Notwithstanding, reports describing its adoption in
      children are still fragmentary and some perplexities have been raised by some
      surgeons. We reviewed our experience with the SILS Palomo varicocelectomy
      procedure (SIL-V) in children and adolescents, comparing this group with a
      similar series operated using conventional laparoscopic varicocelectomy (CL-V).
      PATIENTS AND METHODS: A total of 69 Palomo laparoscopic varicocelectomies were
      performed in patients aged 11-17 years from January 2011 to January 2013.
      Indications for surgery included grades II-III varicocele or ipsilateral
      testicular hypotrophy. The SIL-V procedure was performed in 44 patients with
      roticulating and conventional 5 mm instruments. Testicular vessels were isolated
      "en bloc," clipped and cut. Operating time, visual analogue scale and post
      operative results were compared to a similar group of 25 patients operated with
      CL-V. RESULTS: No patient of the SIL-V group required conversion to conventional
      laparoscopy, none to open surgery. Mean operative time was 22 min (range: 19-28)
      in the SIL-V group, not significantly different compared with CL-V (mean 21 min,
      range: 18-25). All patients experienced a smooth recovery from surgery without
      any complications, and were discharged on day 1. No difficulties were found in
      the SIL-V group. The post-operative pain score was significantly better in SIL-V.
      CONCLUSION: The SIL-V procedure is safe and effective and allows a fast and
      efficient isolation of the vascular bundle. The use of conventional instruments
      is technically feasible in SIL-V.

PMID- 25047309
TI  - Empyema thoracis in children: Still a challenge in developing countries.
AB  - BACKGROUND: To evaluate the effectiveness of surgical intervention in managing
      empyema thoracis in children. PATIENTS AND METHODS: A total of 70 patients aged 1
      14 years diagnosed to have empyema thoracis and who underwent tube thoracostomy
      from January 2010 to December 2013 were studied. All patients of which 12
      patients needed decortication. RESULTS: The mean age of the study group was 5.44
      years and 48.6% were male and 51.4% were female. The most common symptoms at
      admission were fever (90%), dyspnoea (73%), cough (70%) and chest pain (23%).
      Pleural fluid cultures were sterile in 60% of patients. The most frequently
      identified micro-organisms was Staphylococcus aureus (34.2%). Treatment with
      chest tube drainage was successful in 55 (78.6%) patients. Three patients got
      expired. Twelve patients had decortications, all of which were successful. The
      lung re-expansion time was 8.00 +/- 1.68 days (range: 5-13 days) in those
      patients in whom chest tube drainage was successful, whereas it was 7.50 +/-
      2.623 days (range: 4-14 days) in patients in whom decortication was done. The
      post-procedure stay was 10.00 +/- 1.809 days (range: 7-15 days) in patients with
      successful chest tube drainage and 9.5 +/- 2.902 days (range: 6-17 days) in case
      of decortication cases. CONCLUSION: Tube thoracostomy should be done in all cases
      of empyema thoracis regardless of stage, as this leads to reduction in septic
      load. Decision of decortication should be taken without any delay.

PMID- 25047310
TI  - Enteric duplication in children: A case series.
AB  - BACKGROUND: Enteric duplication (ED) cysts include a wide variety of cystic
      lesions, which can involve any part of the gastrointestinal tract (GIT). They can
      be referred to foregut, midgut, hindgut derived, depending upon the portion of
      GIT involved. The main purpose of this study was to document the variety of
      presentation, investigations, and treatment options employed. PATIENTS AND
      METHODS: This was a retrospective study at Paediatric Surgery Department of
      Services Hospital, Lahore from August, 2011 to August, 2013. The details of all
      the patients, including gender, and age, presenting complaint, abdominal
      examination findings, diagnostic modality, site, type, associated malformations,
      surgical option, and outcome were analysed. RESULTS: A total of eight patients
      with histopathological diagnosis of EDs managed were included in the study. Of
      these eight patients, six were males and two were females, with an average age of
      2.4 years. The main diagnostic tool used was ultrasound in almost all patients.
      The most commonly involved site was ileum in 5 of 8 (62.5%) patients. Two cases
      had gastric involvement, while one patient had involvement of the descending
      colon. Six of eight were of tubular type (75%), while remaining 2 (25%) were of
      cystic type. Excision was possible in all these patients. CONCLUSION: ED can
      present with a wide spectrum of symptomatology. It can present as mass abdomen,
      intestinal obstruction or even can mimic as hydrocoele. High index of suspicion
      is therefore required. Ultimate aim of treatment is excision of cyst with
      preservation of vascularity of native gut.

PMID- 25047311
TI  - A prospective comparison of topical feracrylum citrate versus adrenaline as
      haemostatic agent in hypospadias surgery in children.
AB  - BACKGROUND: A comparative study of topical feracrylum citrate versus adrenaline
      to minimise haemorrhage-related complications in paediatric hypospadiac patients.
      PATIENTS AND METHODS: A total of 108 consecutive paediatric hypospadiac patients
      (48 in the study group and 60 control - random allocation) were studied. In the
      study group, 1% feracrylum citrate solution was used and adrenaline (1:100,000)
      in controls. RESULTS: Among the study group, average number of blood-soaked gauge
      pieces were 2.95/patient, correlating with average intraoperative blood loss of
      14.74 ml. In controls, average blood-soaked gauge pieces were 4.83/patient
      corresponding to an average blood loss of 24.13 ml. The average amount of blood
      loss during surgery in the <5 years was 13.70 ml/patient in the feracrylum group,
      while the same in the adrenaline group was 23.45 ml. Average duration of surgery
      was 79 min in the study group, while the same in controls was 94 min/patient.
      Average number of cauterisations was 0.255/patient in the study group and
      0.583/patient among controls. Postoperative haematoma was seen in 8% study group
      compared with 18% controls. Wound oedema appeared in 4.17% study group and 11.67%
      controls. Postoperative complications were higher among controls. CONCLUSIONS:
      Feracrylum is more efficient and safer topical haemostatic agent than adrenaline.
      It reduced the frequency of cauterisation and tissue damage, intraoperative blood
      loss, and postoperative complications.

PMID- 25047312
TI  - Intramuscular compared to intravenous midazolam for paediatric sedation: A study
      on cardiopulmonary safety and effectiveness.
AB  - BACKGROUND: Sedation in children remains a controversial issue in emergency
      departments (ED). Midazolam, as a benzodiazepine is widely used for procedural
      sedation among paediatrics. We compared the effectiveness and safety of two forms
      of midazolam prescription; intramuscular (IM) and intravenous (IV). PATIENTS AND
      METHODS: A cohort study was conducted on two matched groups of 30 children
      referred to our ED between 2010 and 2011. The first group received IM midazolam
      (0.3 mg/kg) and the second group received IV midazolam (0.15 mg/kg) for sedation.
      For evaluating effectiveness, sedation, irritation and cooperation score were
      followed every 15 min for 60 min and for safety assessment, vital signs and O 2
      saturation were observed. RESULTS: Mean age was 6.18 +/- 2.88 years and 31
      patients (51.7%) were male. All patients were sedated completely after using
      first dose. There was an overall complication rate of 68.3%. 35 (58.3%) patients
      presented euphoria as the most common complication, but there was no statistical
      difference between the two groups (P = 0.396). Cases who received IV midazolam
      became sedated faster than those received IM midazolam (P > 0.001). The vital
      signs including heart rate, respiratory rate, systolic blood pressure and O 2
      saturation changed significantly between and within groups during the sedation (P
      < 0.05). CONCLUSION: Both forms of midazolam, IM and IV, are effective and safe
      for paediatric sedation in ED. Although the sedative with IV form might appear
      sooner, IM form of midazolam can be effectively used in patient with limited IV
      access. Patients are better to observe closely for psychological side-effects.

PMID- 25047313
TI  - Tracheobronchial foreign body aspiration in children: A continuing diagnostic
      challenge.
AB  - BACKGROUND: Foreign body aspiration (FBA) is a common cause of respiratory
      compromise in early childhood. The objective of this study was to describe the
      features and outcomes of children with FBA in early and late presentations and to
      examine the reasons for the delay in diagnosis. PATIENTS AND METHODS: This is a
      retrospective review of all children who were admitted with suspected FBA between
      July 2001 and June 2010. Patient's characteristics, history, clinical,
      radiographic, bronchoscopic findings, reason for delay presentation, and
      complications were noted. RESULTS: A total of 158 children admitted to the
      hospital with suspected FBA were included in this study. The average age was 3.28
      years. Forty-eight (30.3%) children were presented late (more than 14 days after
      FBA) and 110 (69.7%) children were presented early (0-14 days). The common
      clinical manifestations of FBA were persistent cough (100%) and choking (72%).
      The most frequent radiological finding observed was air trapping (40%) followed
      by atelectasis (14%). Chest radiographs were normal in 32.2% patients. Ten
      children in early diagnosis group and 29 children in late diagnosis group
      presented with complications. The diagnosis delay was mainly attributed to
      physician misdiagnosis (41.6%). Rigid bronchoscopy was performed in all patients.
      Foreign body was found in all of the cases except six. Watermelon seeds and
      peanuts accounted for 80% of the aspiration. CONCLUSION: FBA is difficult to
      diagnose in children. Delay in diagnosis appears to result from a failure to give
      serious consideration to the diagnosis. Early diagnosis and removal of foreign
      bodies must be achieved to avoid complications.

PMID- 25047314
TI  - Transanal protrusion of intussusceptions in children.
AB  - BACKGROUND: The aim of the following study is to report our management experience
      and outcome of transanal protrusion of intussusceptions. PATIENTS AND METHODS:
      Retrospective analysis of all cases of intussusceptions protruding through the
      anal opening from January 2008 to June 2013. RESULTS: Of 62 cases of
      intussusceptions, transanal protrusion occurred in 10 patients (16% anal
      protrusion rate) with a male:female ratio of 2:3. They were aged 4-96 months
      (mean 22.6 +/- 30.7, median 7.5 months). Six were infants while four were above 1
      year. Duration of symptoms ranged from 2 to 14 days (mean 5.9 days +/- 3.4) with
      only two patients presenting within 48 h. Clinical features included vomiting
      (100%), abdominal pains (100%), bloody mucoid stool (100%), abdominal distension
      (90%), and palpable left iliac fossa mass (70%). Three patients had preceding
      diarrhoea (30%) and two had preceding upper respiratory tract infection (20%).
      Duration of hospital stay ranged from 5 to 23 days (mean 12 days +/- 5.6).
      Findings at surgery included seven ileocolic and two colocolic intussusceptions
      (one patient died before surgery). Operative procedures were right hemicolectomy
      (5), operative manual reduction (3), left hemicolectomy (1) giving a 67% bowel
      resection rate. One patient died giving a 10% mortality rate. CONCLUSION:
      Transanal protrusion occurred more in females and is associated with late
      presentation, older age, high bowel resection rate, and high mortality.

PMID- 25047315
TI  - Tumour necrosis factor-alpha gene polymorphisms in Iranian patients with biliary
      atresia.
AB  - BACKGROUND: Biliary atresia (BA) is a progressive inflammatory destructive
      process of the bile ducts. This study evaluated the relationship between single
      nucleotide polymorphisms in the promoter region of tumour necrosis factor-alpha
      (TNF-alpha) gene and bilaiary atresia. MATERIALS AND METHODS: Genomic
      deoxyribonucleic acid from 16 patients with established diagnosis of BA and 36
      patients with INC was obtained. The genotypes of TNF-alpha-1031 (T/C) and TNF
      alpha-308 (G/A) were determined using the restriction fragment length
      polymorphism-polymerase chain reaction and the results were analysis with proper
      statistic software. RESULTS: The frequencies of T/T, T/C in TNF-alpha-1031 and
      G/G, G/A in TNF-alpha-308 were as same as control group. Moreover, we have same
      deduction for allele frequency and haplotypes analysis (T allele: 84.37%; G
      allele: 87.5%) in BA patients (T allele: 80.56%; G allele: 86.11%) in controls.
      In all cases variants of polymorphism did not affect the severity or incidence of
      BA disease. CONCLUSION: although no significant associations were found between
      BA and control groups, it seems meaningful that since the nature of BA is multi
      factorial. Next step will be considering a new target such as downstream
      modulation of the TNF-alpha pathway or other cytokines and chemokines which act
      directly/indirectly.

PMID- 25047316
TI  - Oesophageal foreign body in children: 15 years experience in a tertiary care
      paediatric centre.
AB  - BACKGROUND: The objective of this study was to report our experience and outcome
      in the management of oesophageal foreign body (EFB) in suspected cases of foreign
      body (FB) ingestion. MATERIALS AND METHODS: Records of children with documented
      EFB ingestion treated in the Department of Pediatric surgery from January 1997 to
      December 2012 were analysed. Diagnosis was made on the basis of history, clinical
      examination and radiological evaluation. Stronger index of suspicion was kept in
      cases of sudden onset of symptoms with an inappropriate history of FB ingestion.
      RESULTS: A total of 317 children underwent emergency rigid oesophagoscopy for
      EFB. Out of these, 206 were males and 111 were females. The most common EFB found
      was coins in 209 (65.9%) cases, followed by food bolus obstruction in 54 (17%),
      metallic FB in 29 (9.1%), plastic FB in 21 (6.6%), and button batteries in 14
      (4.4%) cases. The most common site of FB impaction was found to be cricopharynx
      in 291 (92%) cases. CONCLUSIONS: High index of suspicion should be kept for EFB
      in children who present with unavailable history of FB ingestion. The wait-and
      watch policy in cases of FB oesophagus is not always the correct approach,
      especially when it presents as respiratory distress of sudden onset.

PMID- 25047317
TI  - Complications of peripherally inserted central venous catheters in neonates:
      Lesson learned over 2 years in a tertiary care centre in India.
AB  - BACKGROUND: The objective of this study was to assess the complications of
      peripherally inserted central venous catheters (PICC) in neonates admitted to
      neonatal surgical intensive care unit (NSICU). PATIENTS AND METHODS:
      Retrospective analysis of 237 neonates admitted to NSICU from January 2010 to
      December 2011 was done. RESULTS: Mean age at presentation was 5.8 days and mean
      weight was 1.94 kg. Mean number of attempts was 1.14, mean duration of insertion
      8.4 min and mean duration of patency of catheter 3.14 days. Most common site of
      catheter insertion was upper extremity (basilic followed by cephalic). Overall
      complications were seen in 47 (23%) cases. Infectious complications were seen in
      22 (10.7%) and non-infectious in 25 (12.2%) cases. Significant correlation
      existed between non-infective complications and insertion site (P = 0.03) and
      duration of PICC (P = 0.04). CONCLUSION: Precautions should be taken and position
      must be confirmed during and after PICC insertion to avoid undue complications.

PMID- 25047318
TI  - Effect of surgical techniques on long-term outcome in congenital pouch colon: A
      tertiary care centre experience.
AB  - BACKGROUND: The objective of the following study is to assess effect of a novel
      surgical technique on long-term outcome in operated cases of congenital pouch
      colon (CPC). PATIENTS AND METHODS: We retrospectively analysed our surgical
      neonatal records from June 2002 to May 2012. Out of 477 cases of anorectal
      malformations, CPC was found in 73 (15%) cases. Out of 73 cases of CPC, 39
      (53.4%) were complete pouch and 34 (46.6%) were incomplete. In addition to
      invertogram, an erect skiagram was done in all cases to confirm diagnosis.
      Patients were operated either by single stage pull-through or by staged procedure
      using conventional abdominoperineal (AP) pull-through or by our new hanging bowel
      technique. All patients were put on bowel management programme starting 1 month
      post-surgery until 5 years of life. RESULTS: Children presented to us at median
      age of 2.1 days. Mean weight at time of presentation was 2.74 kg. In our study,
      group median age at time of initial procedure was 2.7 days. In staged procedures
      definitive surgery was done after 6 months. Hospital stay in single stage
      procedure using the hanging bowel technique was 9.7 days while 17.4 days in
      conventional AP pull-through. Complication rate were high in conventional pull
      through when compared to hanging bowel technique as shown by the significant P <
      0.05. CONCLUSION: Our novel surgical technique for pull-through is suitable for
      both single stage as well as staged pull-through. Bowel enema programme should be
      an integral part of management of CPC.

PMID- 25047319
TI  - Foreign body in the bronchus in children: 22 years experience in a tertiary care
      paediatric centre.
AB  - BACKGROUND: Our objective was to assess types, presentation, duration of symptoms
      and usefulness of rigid bronchoscopy for diagnosis and treatment of bronchial
      foreign body (FB) in children. MATERIALS AND METHODS: Records of children with
      documented FB aspiration treated in Department of Paediatric Surgery from January
      1991 to December 2012 were analysed retrospectively. Diagnosis was made on the
      basis of history, clinical examination, radiological evaluation and bronchoscopy.
      RESULTS: A total of 196 children underwent emergency rigid bronchoscopy for
      suspected bronchial FB and in 173 cases FB was found. Out of 173 cases, 118
      (68.21%) were males and 55 (31.79%) were females. Mean age was 3.7 years (range:
      2 months-12 years) while mean duration of symptoms was 28 h (range: from 3 h to 4
      months). Most common FB bronchus found was peanut 141 (81.50%). FB was localised
      to right bronchus in 112 (64.74%) cases while in 44 (25.43%) cases left bronchus
      was involved. In 17 (9.83%) cases FB was seen at carina only. Cough was the most
      common presenting symptom in 131 (75.72%) cases. The most common finding in chest
      X-ray was consolidation-collapse lung or emphysematous lung in 83 (47.97%) cases
      followed by the flattening of the diaphragm in 17 (9.83%) cases. In 35 (20.23%)
      cases chest X-ray was found to be normal. Pre-operative endotracheal intubation
      was done in 13 (7.51%) cases while 20 (11.56%) cases required post-operative
      mechanical ventilation. CONCLUSION: High index of suspicion should be kept for
      bronchial FB in children who present with suggestive history of FB ingestion even
      with normal physical and radiological evaluation.

PMID- 25047320
TI  - Umbilicoplasty in children with huge umbilical hernia.
AB  - BACKGROUND: Huge umbilical hernias (HUH) are voluminous umbilical hernia (UH)
      that are frequent in black African children. Several surgical techniques are used
      in their treatment for umbilical reconstruction, but techniques using skin flaps
      provide better aesthetic results. In this study, we presented our technique of
      umbilicoplasty in HUH, and its results. PATIENTS AND METHODS: It is a
      retrospective study on children treated for HUH, from January 2012 to December
      2013. The UH was called HUH when its basis diameter (BD) exceeds 3 cm. Every HUH
      was characterised by its height, BD and morphology. Our technique was a two
      lateral flaps technique; the flaps are symmetrical and drawn so as to
      reconstitute the different parts of the umbilicus. The results were appreciated
      with criteria, including the peripheral ring and the central depression of the
      neo-umbilicus. RESULTS: Twelve children were concerned (7 boys and 5 girls).
      Their mean age was 5 years and 6 months. The mean BD was 5.6 cm (extremes 3 and 8
      cm), and the mean height of the HUH was 7.45 cm (extremes 3 and 9 cm). All
      underwent umbilicoplasty. In early post-operative period, two children presented
      a transitory subcutaneous hematoma. Late complications were granulation tissue
      with two children, and cheloid scar with one. With a mean follow-up of 10 months,
      we had 10 excellent results and two fair results according to our criteria.
      CONCLUSION: Our two lateral flaps umbilicoplasty is well-adapted to HUH in
      children. It is simple and assures a satisfactory anatomical and cosmetic result.

PMID- 25047321
TI  - A child with colo-colonic intussusception due to a large colonic polyp: Case
      report and literature review.
AB  - Colo-colonic intussusception (CI) due to a colonic polyp is a rarely reported
      cause of intestinal obstruction in school-aged children. Hydrostatic reduction
      (HR) and endoscopic polypectomy are minimally invasive and technically feasible
      for treating CI. We report a case of CI and review the literature, focusing on
      the diagnosis and treatment. 

PMID- 25047322
TI  - Intestinal obstruction secondary to infantile polyarteritis nodosa.
AB  - Polyarteritis Nodosa (PAN) is a rare systemic necrotising vasculitis of medium
      and small-sized arteries. Patients typically present with systemic symptoms.
      Obstructive intestinal symptoms are described but usually resolve with treatment
      of the underlying vascular disease. We report a case of a one year old boy with
      multiple ischemic small bowel strictures secondary to infantile PAN, who was
      treated with resection of the affected segments by single port laparoscopy. 

PMID- 25047323
TI  - Gastric duplication cyst: A cause of rectal bleeding in a young child.
AB  - Gastric duplication cysts are an uncommon congenital anomaly and rectal bleeding
      is a rare presentation of a complicated gastric duplication cyst. This case
      report describes the radiological findings in a child with a complicated gastric
      duplication cyst. 

PMID- 25047324
TI  - Crossed testicular ectopia: Report of six cases.
AB  - Crossed testicular ectopia or transverse testicular ectopia is an extremely rare
      anomaly characterised by migration of one testis towards the opposite inguinal
      canal, usually associated with unilateral inguinal hernia. This report describes
      six cases of crossed ectopic testes, one of the largest series, and with unusual
      clinical histories. 

PMID- 25047325
TI  - Knotting of a nasogastric feeding tube in a child with head injury: A case report
      and review of literature.
AB  - Nasogastric intubation is one of the most common routine nonoperative procedures
      available for the hospital care of patients. The insertion and removal of this
      tube is associated with many complications. The complications include trauma,
      nasal septal abscess and inadvertent entry into the cranial cavity and trachea,
      ulceration, bleeding from varices and perforation. Knotting of the nasogastric
      tube is one of the very rare complications of nasogastric intubation particularly
      in children. To the best of our knowledge there are very few reported cases in
      children. The technique used in the patient was the application of a steady tug
      which allows the lower oesophageal sphincter to open, therefore enabling the
      removal of the nasogastric tube. The possible predispositions to knotting of a
      nasogastric tube include small bore tubes, excess tube length and gastric
      surgery. We postulate that reduced gastric tone is another possible predisposing
      factor with head injury being the most likely reason in the index patient. We
      also challenge the fact that the small sized stomach is a risk factor for
      knotting of a feeding tube if the functional status and tone are normal, because
      of the rarity in children. 

PMID- 25047326
TI  - Noncommunicating multiple intra-abdominal enteric duplication cysts.
AB  - A very rare case of noncommunicating multiple intra and retroperitoneal enteric
      duplication cysts (EDCs) is reported and discussed. Two large noncommunicating
      EDCs, one within the mesentery of proximal jejunum causing complete luminal
      obstruction and other isolated cyst in retroperitoneal area displacing duodenum
      and extrahepatic biliary system, were resected successfully in a 2-day-old
      neonate along with correction of malrotation. 

PMID- 25047327
TI  - Schistosomiasis and abdominal mass.

PMID- 25047328
TI  - A flexible, multifaceted approach is needed in health technology assessment of
      PET.

PMID- 25047329
TI  - Preparation and preliminary evaluation of 63Zn-zinc citrate as a novel PET
      imaging biomarker for zinc.
AB  - Abnormalities of zinc homeostasis are indicated in many human diseases. A
      noninvasive imaging method for monitoring zinc in the body would be useful to
      understand zinc dynamics in health and disease. To provide a PET imaging agent
      for zinc, we have investigated production of (63)Zn (half-life, 38.5 min) via the
      (63)Cu(p,n)(63)Zn reaction using isotopically enriched solutions of (63)Cu-copper
      nitrate. A solution target was used for rapid isolation of the (63)Zn
      radioisotope from the parent (63)Cu ions. Initial biologic evaluation was
      performed by biodistribution and PET imaging in normal mice. METHODS: To produce
      (63)Zn, solutions of (63)Cu-copper nitrate in dilute nitric acid were irradiated
      by 14-MeV protons in a low-energy cyclotron. An automated module was used to
      purify (63)Zn from (63)Cu in the target solution. The (63)Cu-(63)Zn mixture was
      trapped on a cation-exchange resin and rinsed with water, and the (63)Zn was
      eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized
      with NaHCO3, and the (63)Zn was then trapped on a carboxymethyl cartridge, washed
      with water, and eluted with isotonic 4% sodium citrate. Standard quality control
      tests were performed on the product according to current good manufacturing
      practice, including radionuclidic identity and purity, and measurement of
      nonradioactive Zn(+2), Cu(+2), Fe(+3), and Ni(+2) by ion-chromatography high
      performance liquid chromatography. Biodistribution and PET imaging studies were
      performed in B6.SJL mice after intravenous administration of (63)Zn-zinc citrate.
      (63)Cu target material was recycled by eluting the initial resin with 4N HNO3.
      RESULTS: Yields of 1.07 +/- 0.22 GBq (uncorrected at 30-36 min after end of
      bombardment) of (63)Zn-zinc citrate were obtained with a 1.23 M (63)Cu-copper
      nitrate solution. Radionuclidic purity was greater than 99.9%, with copper
      content lower than 3 MUg/batch. Specific activities were 41.2 +/- 18.1 MBq/MUg
      (uncorrected) for the (63)Zn product. PET and biodistribution studies in mice at
      60 min showed expected high uptake in the pancreas (standard uptake value, 8.8 +/
      3.2), liver (6.0 +/- 1.9), upper intestine (4.7 +/- 2.1), and kidney (4.2 +/-
      1.3). CONCLUSION: A practical and current good manufacturing practice-compliant
      preparation of radionuclidically pure (63)Zn-zinc citrate has been developed that
      will enable PET imaging studies in animal and human studies. (63)Zn-zinc citrate
      showed the expected biodistribution in mice.

PMID- 25047330
TI  - Dosimetric differences between intraoperative and postoperative plans using Cs
      131 in transrectal ultrasound-guided brachytherapy for prostatic carcinoma.
AB  - The aim of the study was to investigate the differences between intraoperative
      and postoperative dosimetry for transrectal ultrasound-guided transperineal
      prostate implants using cesium-131 ((131)Cs). Between 2006 and 2010, 166 patients
      implanted with (131)Cs had both intraoperative and postoperative dosimetry
      studies. All cases were monotherapy and doses of 115 were prescribed to the
      prostate. The dosimetric properties (D90, V150, and V100 for the prostate) of the
      studies were compared. Two conformity indices were also calculated and compared.
      Finally, the prostate was automatically sectioned into 6 sectors (anterior and
      posterior sectors at the base, midgland, and apex) and the intraoperative and
      postoperative dosimetry was compared in each individual sector. Postoperative
      dosimetry showed statistically significant changes (p < 0.01) in every dosimetric
      value except V150. In each significant case, the postoperative plans showed lower
      dose coverage. The conformity indexes also showed a bimodal frequency
      distribution with the index indicating poorer dose conformity in the
      postoperative plans. Sector analysis revealed less dose coverage postoperatively
      in the base and apex sectors with an increase in dose to the posterior midgland
      sector. Postoperative dosimetry overall and in specific sectors of the prostate
      differs significantly from intraoperative planning. Care must be taken during the
      intraoperative planning stage to ensure complete dose coverage of the prostate
      with the understanding that the final postoperative dosimetry will show less dose
      coverage.

PMID- 25047331
TI  - Modelling the progression of bird migration with conditional autoregressive
      models applied to ringing data.
AB  - Migration is a fundamental stage in the life history of several taxa, including
      birds, and is under strong selective pressure. At present, the only data that may
      allow for both an assessment of patterns of bird migration and for retrospective
      analyses of changes in migration timing are the databases of ring recoveries. We
      used ring recoveries of the Barn Swallow Hirundo rustica collected from 1908-2008
      in Europe to model the calendar date at which a given proportion of birds is
      expected to have reached a given geographical area ('progression of migration')
      and to investigate the change in timing of migration over the same areas between
      three time periods (1908-1969, 1970-1990, 1991-2008). The analyses were conducted
      using binomial conditional autoregressive (CAR) mixed models. We first
      concentrated on data from the British Isles and then expanded the models to
      western Europe and north Africa. We produced maps of the progression of migration
      that disclosed local patterns of migration consistent with those obtained from
      the analyses of the movements of ringed individuals. Timing of migration
      estimated from our model is consistent with data on migration phenology of the
      Barn Swallow available in the literature, but in some cases it is later than that
      estimated by data collected at ringing stations, which, however, may not be
      representative of migration phenology over large geographical areas. The
      comparison of median migration date estimated over the same geographical area
      among time periods showed no significant advancement of spring migration over the
      whole of Europe, but a significant advancement of autumn migration in southern
      Europe. Our modelling approach can be generalized to any records of ringing date
      and locality of individuals including those which have not been recovered
      subsequently, as well as to geo-referenced databases of sightings of migratory
      individuals. 

PMID- 25047332
TI  - Factors affecting outcome in acute hypertriglyceridemic pancreatitis treated with
      plasma exchange: an observational cohort study.
AB  - OBJECTIVES: The optimal therapy for hypertriglyceridemic acute pancreatitis,
      especially the role of plasma exchange (PE), is not entirely clear. The aim of
      our large, single-center, observational, cohort study was to analyze the factors
      affecting outcome in hypertriglyceridemic pancreatitis treated with PE. METHODS:
      We included 111 episodes of hypertriglyceridemic pancreatitis treated with PE,
      which occurred in 103 different patients. The Acute Physiology and Chronic Health
      Evaluation (APACHE) II score, triglycerides, delay to first PE, and PE treatment
      details were retrospectively obtained from the patients' records. The main
      outcome measures were length of hospitalization and in-hospital mortality.
      RESULTS: The patients were 47+/-9 years old and the median APACHE II score at
      first PE was 4 (inter-quartile range (IQR) 2-7). There was a seasonal variation
      in the incidence of hypertriglyceridemic pancreatitis, and the recurrence rate
      was 1.6% per year. Triglycerides at presentation did not correlate with APACHE II
      or influence the outcome. The mean reduction in triglycerides during PE was 59%
      (from 44+/-31 to 18+/-15 mmol/l), which was twice the reduction observed during
      conservative treatment (27% daily). The median hospital stay was 16 days (IQR 10
      24) and in-hospital mortality was 5%. The median delay to first PE was 35 hours
      (IQR 24-52), and there was no difference in mortality in the early and late PE
      groups (7% vs. 6%, p = 0.79). The group with citrate anticoagulation during PE
      had a significantly lower mortality than the group with heparin anticoagulation
      (1% vs. 11%, p = 0.04), and citrate was an independent predictor also in the
      multivariate model (p = 0.049). CONCLUSIONS: PE effectively reduced serum
      triglycerides faster than could be expected with conservative treatment. The
      delay in PE therapy did not influence survival. We found that citrate
      anticoagulation during PE was associated with reduced mortality, which should be
      confirmed in a randomized study.

PMID- 25047334
TI  - The butterfly fragment in comminuted femoral shaft fracture may be movable
      following intramedullary nail treatment.
AB  - The gap among fracture fragments is an important factor which influences the
      healing of bone fracture, and it may be changeable during the early phase of bone
      healing. In this letter, we pointed out our view that the gap between the
      butterfly fragment, and the shaft in femoral shaft fractures can easily be
      changed, so it is hard to study the potential correlation between the size of the
      gap and fracture healing. 

PMID- 25047333
TI  - Radiological outcome and intraoperative evaluation of a computer-navigation
      system for femoral nailing: a retrospective cohort study.
AB  - AIM: Intraoperative determinations of femoral antetorsion and leg length during
      fixation of femoral shaft fractures present a challenge. In femoral shaft
      fracture fixations, a computer-navigation system has shown promise in determining
      antetorsion and leg length discrepancies. This retrospective cohort study aimed
      to determine whether the use of computer navigation during femoral nailing
      procedures reduced postoperative femoral malrotation and leg length discrepancy,
      as well as the number of revision cases. We also sought to determine whether
      radiation exposure time was reduced when computer navigation was used. MATERIALS
      AND METHODS: Of 246 patients treated for femoral shaft fractures between 2004 and
      2012, we selected those that received postoperative computed tomography for
      rotation and leg length control. We included 24 patients who received navigation
      assisted treatments and 48 who received unassisted treatments, matched for age,
      sex, and fracture type. All patients were treated by femoral nailing. RESULTS:
      The groups showed significant differences in the mean (standard deviation (SD)
      delay before surgery (navigation-assisted vs. unassisted groups: 8.5 +/- 3.2 vs.
      5.2 +/- 5.8 days; P<0.05) and surgery times (163.7 +/- 43.94 vs. 98.3 +/- 28.13
      min; P<0.001). The groups were significantly different in the mean (SD) radiation
      exposure time (4.43 +/- 1.35 vs. 3.73 +/- 1.5 min; P=0.042), and were not
      significantly different in the postoperative femoral antetorsion difference (8.83
      +/- 5.52 degrees  vs. 12.4 +/- 9.2 degrees ; P=0.056), or in the postoperative
      length discrepancy (0.92 +/- 0.75 vs. 0.95 +/- 0.94 cm; P=0.453). Four (16.7%)
      navigation-assisted and 15 (31.25%) unassisted surgeries got revision for torsion
      and/or length corrections. CONCLUSION: Our results showed that, compared to
      unassisted femoral surgery, the computer-navigation system did not improve
      postoperative results or reduce radiation exposure. In the future, improvements
      in handling and application could facilitate the workflow and may provide better
      postoperative results. Currently, computer navigation may provide advantages for
      complicated or sophisticated cases, such as complex three-dimensional deformity
      corrections. LEVEL OF EVIDENCE: Level III.

PMID- 25047336
TI  - Resuscitating inpatient clinical clerkships: a medical student perspective.

PMID- 25047335
TI  - The epidemiology of firework-related injuries in the United States: 2000-2010.
AB  - INTRODUCTION: The purpose of this study is to examine the epidemiology of
      firework-related injuries among an emergency department (ED) nationally
      representative population of the United States for the years 2000-2010, including
      whether the type of firework causing the injury is differential by patient
      demographics and whether the severity of injury is associated with the firework
      type. METHODS: The data analysed in this study was collected from the Consumer
      Product Safety Commission's (CPSC's) National Electronic Injury Surveillance
      System (NEISS). RESULTS: A total of 2812 injuries represented an estimated 97,562
      firework-related injuries treated in emergency departments within the United
      States from 2000 to 2010. The incidence generally decreased over time. With
      respect to age, the rate was higher for children, with the highest rates being
      observed for 10-19 year olds (7.28 per 100,000 persons) and 0-9 year olds (5.45
      per 100,000 persons). The injury rate was nearly three times higher for males
      compared to the female counterparts (4.48 vs. 1.57 per 100,000 persons). Females
      were less likely than males to severely injure themselves with all types of
      fireworks besides sparklers/novelty devices (OR 1.08, CI 0.26-4.38). DISCUSSION:
      The results from this suggest that firework-related injuries have decreased by
      nearly 30% over the 11-year period between 2000 and 2010. Moreover, there has
      been a decreasing trend in the type of firework causing injury for every firework
      type excluding the unspecified firework type. However, adolescents of 10-19 years
      old had the highest rate of injury for fireworks over the 11-year period. In
      addition odds of injury are differential by firework type. CONCLUSION:
      Understanding the specific types of fireworks may lead to better preventative
      methods and regulations. Moreover, preventative methods should be taken to reduce
      the rate of firework-related injuries among U.S. youths [1], and possibly more
      regulations and enforcement of laws geared towards prohibiting novice use of
      fireworks.

PMID- 25047337
TI  - New affiliation.

PMID- 25047338
TI  - The history of PDT in Norway Part II. Recent advances in general PDT and ALA-PDT.
AB  - Generation of singlet oxygen and estimation of its lifetime, the oxygen effect,
      the subcellular localization of photosensitizers and their photodegradation
      during photodynamic therapy (PDT), the effects of PDT on DNA and chromosomes were
      described in the first part of our review. In this review we discuss PDT in
      combination with other treatments (hyperthermia, ionizing radiation,
      electrotherapy, chemotherapeutic drugs) or with other agents; cell interactions
      and bystander effects in PDT; the influence of PDT on the cytoskeleton; a novel
      technology, named photochemical internalisation (PCI), for light-induced delivery
      of macromolecules and 5-aminolevulinic acid (ALA) PDT. Lipophilic derivatives of
      ALA, instead of ALA itself, were proposed for induction of protoporphyrin IX
      (PpIX) in the treatment of superficial lesions. Based on this research a
      Norwegian company PhotoCure ASA was founded in 1993 with the aim to commercialise
      photodynamic technologies developed at the Norwegian Radium Hospital, the largest
      comprehensive cancer centre in Northern Europe. The company has two products on
      the market: Metvix((r)) for treatment of basal cell carcinomas and actinic
      keratoses, and Hexvix((r)) for fluorescence diagnosis of bladder cancer. New ALA
      derivatives for fluorescence diagnosis and treatment of early-stage cancers in
      internal organs, e.g. colon cancer, are currently being investigated. 

PMID- 25047339
TI  - Combination of immunotherapy and photodynamic therapy in the treatment of
      Bowenoid papulosis.
AB  - OBJECTIVE: To investigate the feasibility and efficacy of combination of
      imiquimod and 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for
      the treatment of genital Bowenoid papulosis (BP). MATERIALS AND METHODS: A total
      of 27 BP patients were randomized into two groups. Fifteen (12 male and 3 female,
      age 22-56 years old) were treated with topical application of 5% imiquimod cream
      (three times a week) and ALA-PDT (100J/cm(2) at 100mW/cm(2), once a week) for 1-4
      times. For comparison, other 12 (6 male and 6 female, age 29-58 years old) were
      treated with CO2 laser vaporization as a control. Patients were followed up for 3
      12 months. Biopsies were taken from BP lesions prior to treatment and tested for
      HPV-16 and HPV-18 DNA. RESULTS: In combined therapy group, 60% (9/15) patients
      showed complete remission and only one recurred (11.1%) during follow up. Local
      side effects included mild erythema, edema, erosion and burning and/or stinging
      sensation. No systemic side effect was found. In CO2 laser vaporization group,
      83.3% (10/12) patients showed complete remission. However, recurrence occurred in
      six patients (60.0%). Local side effects included mild to moderate edema,
      erosion, ulceration, delayed healing, prolonged pain and scarring. The difference
      of recurrence rate between two groups was statistically significant (P<0.05).
      CONCLUSION: Topical application of imiquimod cream and ALA-PDT is safe, effective
      and associated with low recurrence and less side effect.

PMID- 25047340
TI  - Invited comments.

PMID- 25047341
TI  - Microvascular effects of Photofrin((r))-induced photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVE: The object of our study is to evaluate the feasibility
      of photodynamic therapy (PDT) for complicated hemangiomas. The photosensitizing
      activities of Photofrin((r)) have been used in vivo models for our goal of
      evaluation. STUDY DESIGN/MATERIALS AND METHODS: The in vivo biological activities
      of Photofrin((r)) exposed to the total laser energy density of 100J/cm(2) with
      the power density of 100 or 120mW/cm(2) at 630nm wavelength was studied. The
      amount of vascular damage produced in the chick chorioallantoic membrane (CAM)
      was evaluated. At 630nm wavelength, those individual vessels with a diameter of
      40MUm or less and those with a diameter between 40 and 100MUm were treated with
      Photofrin((r)) at a concentration of about 2.5mg/mL, and injected
      intraperitoneally at 2.5mg/kg, illuminated at 100 and 120mW/cm(2), respectively.
      Both exhibited coagulation. RESULTS: There were no statistically significant
      differences between the two groups (100 and 120mW/cm(2)) on vessel damage grade
      1. With vessel damage grades 2 and 3, the differences were statistically
      significant between two groups. Vessel damages between arterioles and venules
      also demonstrated differences in the 100mW/cm(2) treated group but not in the
      120mW/cm(2) group. Statistically significant differences were also shown in
      arteriole and venules damage between 100 and 120mW/cm(2) treated groups. The
      severity of vessel damage between grades 1 and 2, 1 and 3, and 2 and 3, were
      compared. The differences were statistically significant in 100mW/cm(2) treated
      group. There was no statistically significant difference in 120mW/cm(2) treated
      group. CONCLUSION: Photofrin((r)) has the capabilities for destruction of
      microvascular vessels of CAM. Extension of this study to the second-generation
      photosensitizers is underway. The most important treatment variables seem to be
      the power density.

PMID- 25047342
TI  - Efficacy of ZnPcS2P2 photodynamic therapy solely or with tumor vaccines on mouse
      tumor models.
AB  - BACKGROUND AND OBJECTIVES: Granulocyte-macrophage colony-stimulating factor (GM
      CSF) and B7.1 transduced tumor vaccine cells could induce efficient anti-tumor
      immune response. It is interesting to study whether they could be an adjuvant to
      photodynamic therapy (PDT). Recent in vitro study proved that novel
      photosensitizer ZnPcS2P2 has capability of effective photodynamic killing of
      leukemic cells. In this preliminary study, we evaluated the photodynamic efficacy
      of ZnPcS2P2 on two tumor models and the improving anti-tumor efficacy of PDT in
      combination with GM-CSF gene-transduced vaccine and B7.1 gene-transduced vaccine.
      METHODS: Nude mice bearing human leukemia xenograft and C57BL/6 mice bearing EL-4
      thymic lymphoma were used to evaluate photodynamic efficacy of ZnPcS2P2. The EL-4
      thymic lymphoma was used to test the improving anti-tumor efficacy of ZnPcS2P2
      PDT in combination with GM-CSF gene-transduced vaccine and B7.1 gene-transduced
      vaccine. Each vaccine was administered near the tumor bed three times: 2 days
      before PDT, 0 and 2 days after PDT. RESULTS: ZnPcS2P2-PDT could significantly
      reduce tumor growth and prolong the survival time in both tumor models. Improving
      anti-tumor efficacy of ZnPcS2P2-PDT was demonstrated when utilizing GM-CSF
      transduced vaccine and B7.1-transduced vaccine prior to and after ZnPcS2P2-PDT in
      lymphoma-bearing mice. Twenty-five percent of lymphoma-bearing mice were
      completely cured with a combination of PDT and vaccine cells. CONCLUSIONS:
      ZnPcS2P2-PDT may be a beneficial treatment for hemotopoietic malignance. GM-CSF
      transduced vaccine and B7.1-transduced vaccine could strengthen ZnPcS2P2-PDT
      elicited anti-lymphoma potency.

PMID- 25047343
TI  - Two-photon excitation studies of m-THPC photosensitizer and photodynamic activity
      in an epithelial cell line.
AB  - A femtosecond laser delivering pulses of wavelength 800nm and 124fs duration at
      rates of 1kHz has been used to investigate the two-photon excited fluorescence in
      the photosensitizer m-THPC. The scaling of fluorescence amplitude with laser
      power and fluorescence sidelight imaging are found to support a predominantly two
      photon excitation mechanism. A value for the two-photon cross-section of
      delta=1.8*10(-57)m(4)s is derived by comparing the fluorescence signals excited
      by wavelengths of 800 and 400nm. Preliminary results demonstrating the two-photon
      induced PDT activity of m-THPC in an epithelial cell line are also reported. 

PMID- 25047344
TI  - Fluorescence diagnosis of cervical squamous intraepithelial lesions: A clinical
      feasability study.
AB  - The potential of fluorescence diagnosis (FD) is still undeveloped in gynaecology.
      In order to diagnose and localize squamous intraepithelial lesion (SIL) of the
      cervix, a new method improving the low specificity of colposcopy, would be
      useful. OBJECTIVE: The goal of this study was to assess the feasability and
      safety of colposcopic FD of SIL after topicaly application of methyl
      aminolevulinate (MAL). MATERIALS AND METHODS: Patients with histologic proved
      cervical intraepithelial neoplasia (CIN) and planned for loop electrosurgical
      excision procedure (LEEP) under general anesthesia, were included in a
      prospective study. Before general anesthesia, a thick layer of MAL (Metvix((r))
      160mg/mL cream) was applied on the cervix for 35-150min. Fluorescent colposcopic
      inspection of the cervix was performed using a rigid 10-mm laparoscope inserted
      in the vaginal cavity and connected to D-light AF system (Karl Storz Endoskope,
      Tuttlingen Germany). In order to confirm neoplasic status, fluorescent foci
      underwent directed punch biopsy(ies). RESULTS: Fourteen patients were included in
      the study. Colposcopic fluorescence imaging revealed red fluorescent foci in
      71.4% of cases (10/14) (neoplasic status of fluorescent foci was confirmed in
      80%). Concerning ME-ALA, the mean of application time was 73min (35-150). Two
      cases presented a false-positive fluorescence and four cases of false-negative
      fluorescence. For all cases of false-negative fluorescence, application time of
      MAL was less than 60min. We observed no systemic or local toxicity of MAL
      application in any of the groups. CONCLUSION: Using topical application of MAL to
      the cervix, we demonstrated that FD of SIL is feasible. This study justifies the
      further development of fluorescence imaging that combines classical white light
      colposcopy with the use of a photosensitizer.

PMID- 25047345
TI  - Photodynamic effects of a novel series of silicon(IV) phthalocyanines against
      human colon adenocarcinoma cells.
AB  - The photodynamic activities of a novel series of silicon(IV) phthalocyanines with
      different axial substituents including the 1,3-bis(dimethylamino)-2-propoxy
      group, isopropylidene-protected galactose, and polyethylene glycol have been
      investigated against HT29 and T84 human colon adenocarcinoma cells. While these
      compounds are not cytotoxic in the absence of light, they exhibit high
      photocytotoxicities with IC50 values as low as 17nM. The photodynamic activities
      of these compounds against HT29 are correlated with the cellular uptake as
      reflected by the relative intracellular fluorescence intensity and the Q-band
      absorbance of the dyes in the organic extracts. The most potent compound 1,
      having a 1,3-bis(dimethylamino)-2-propoxy group and a methoxy group as the axial
      substituents, has a high and selective affinity to the mitochondria of HT29
      cells, as revealed by fluorescence microscopy. 

PMID- 25047346
TI  - Role of Fourier transform infrared spectroscopy (FTIR) in the diagnosis of
      parathyroid pathology.
AB  - BACKGROUND: With the advent of minimally invasive parathyroid surgery (MIPS)
      accurate pathological diagnosis to differentiate parathyroid adenomas from
      hyperplasia has become difficult for the pathologist. This is because now single
      glands are excised, guided by better preoperative localisation scans, while for
      an accurate pathological diagnosis, at least a two-gland biopsy is required.
      Ultimately, an accurate pathological diagnosis to establish the aetiology is
      essential for the management of hyperparathyroidism. To resolve this issue we
      evaluated the ability of FTIR to accurately differentiate between parathyroid
      adenoma and hyperplasia using their biochemical signatures. METHODS: Samples of
      diseased glands were collected intraoperatively from consenting patients over a 1
      year period. Sixteen glands were analysed - eight hyperplasias and eight
      adenomas. Samples were analysed using an infrared spectroscope and reflected the
      biochemical nature of the sample tissue. Spectra collected were subjected to both
      empirical and multivariate analytical techniques. RESULTS: Empirical analysis
      highlighted differences in spectral protein peaks, with possibly additional
      subtle differences in nucleic acid spectra between the pathologies. A
      multivariate statistical predictive model demonstrated the sensitivity of FTIR
      for adenomas to be 93% and hyperplasia 93%, (88% on cross validation testing).
      CONCLUSIONS: Thus, infrared spectroscopy is potentially an excellent tool to
      differentiate the two pathologies and could be a useful adjunct to the
      pathological diagnosis of single glands.

PMID- 25047347
TI  - Effect of vehicles and esterification on the penetration and distribution of
      hypericin in the skin of hairless mice.
AB  - To study the in vivo penetration and skin distribution of hypericin, the compound
      (0.1%) was formulated in 10 different vehicles that are commonly used in
      pharmaceutical compounding, and applied on the skin of hairless mice for 4h.
      After application of hypericin in PEG ointment, white petrolatum or unguentum
      emulsificans, fluomicroscopic analysis of skin sections revealed penetration to
      be confined to the stratum corneum. On the contrary, Beeler base, unguentum
      sorbatis 100 and cremor non ionicus caused penetration of hypericin in the viable
      epidermis. To reduce the prominent depot formation in the stratum corneum, which
      was observed irrespectively of the formulation applied, hypericin was esterified
      into its hydrolyzable acetate derivative. The influence of esterification proved
      to be substantial when hypericin acetate (0.15%) was incorporated in unguentum
      sorbatis 100, as hypericin-related fluorescence could be detected deeply within
      the dermis. Moreover, accumulation in the sebaceous glands was found to be
      prominent. These results indicate the value of further studies regarding the
      application of hypericin and hypericin acetate as topical photosensitizers for
      photodynamic therapy. 

PMID- 25047348
TI  - Conference Report on the 11th World Congress of the International Photodynamic
      Association (IPA), Shanghai, March 28th-31st, 2007.

PMID- 25047350
TI  - Genotoxicity of phenacetin in the kidney and liver of Sprague-Dawley gpt delta
      transgenic rats in 26-week and 52-week repeated-dose studies.
AB  - Transgenic rat mutation assays can be used to assess genotoxic properties of
      chemicals in target organs for carcinogenicity. Mutations in transgenes are
      genetically neutral and accumulate during a treatment period; thus, assays are
      suitable for assessing the genotoxic risk of chemicals using a repeated-dose
      treatment paradigm. However, only a limited number of such studies have been
      conducted. To examine the utility of transgenic rat assays in repeated-dose
      studies, we fed male and female Sprague-Dawley gpt delta rats with a 0.5%
      phenacetin-containing diet for 26 and 52 weeks. A long-term feeding of phenacetin
      is known to induce renal cancer in rats. Phenacetin administration for 52 weeks
      in males significantly increased gpt (point mutations) mutant frequency (MF) in
      the kidney, the target organ of carcinogenesis. In the liver, the nontarget organ
      of carcinogenesis, gpt MFs were significantly elevated in phenacetin treatment
      groups of both genders during 26- and 52-week treatments. Furthermore, sensitive
      to P2 interference (Spi(-)deletions) MF increased in the liver of both genders
      following 52-week treatment. MFs were higher after treatment for 52 weeks than
      after treatment for 26 weeks. Frequencies of phenacetin-induced mutations were
      higher in the liver than in the kidney, suggesting that the intensity of
      genotoxicity does not necessarily correlate with the induction of tumor
      formation. Results from gpt delta rat assays of repeated-dose treatments are
      extremely useful to elucidate the relationship between gene mutations and
      carcinogenesis in the target organ induced by cancer-causing agents. 

PMID- 25047349
TI  - Gene expression profiling of peri-implant healing of PLGA-Li+ implants suggests
      an activated Wnt signaling pathway in vivo.
AB  - Bone development and regeneration is associated with the Wnt signaling pathway
      that, according to literature, can be modulated by lithium ions (Li+). The aim of
      this study was to evaluate the gene expression profile during peri-implant
      healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+,
      while PLGA without Li+ was used as control, and a special attention was then paid
      to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28
      days and the gene expression profile was investigated using a genome-wide
      microarray analysis. The results were verified by qPCR and immunohistochemistry.
      Histomorphometry was used to evaluate the possible effect of Li+ on bone
      regeneration. The microarray analysis revealed a large number of significantly
      differentially regulated genes over time within the two implant groups. The Wnt
      signaling pathway was significantly affected by Li+, with approximately 34% of
      all Wnt-related markers regulated over time, compared to 22% for non-Li+
      containing (control; Ctrl) implants. Functional cluster analysis indicated
      skeletal system morphogenesis, cartilage development and condensation as related
      to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein
      encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl.
      The presence of beta-catenin, FOSL1 and ASPN positive cells was confirmed around
      implants of both groups. Interestingly, a significantly reduced bone area was
      observed over time around both implant groups. The presence of periostin and
      calcitonin receptor-positive cells was observed at both time points. This study
      is to the best of the authors' knowledge the first report evaluating the effect
      of a local release of Li+ from PLGA at the fracture site. The present study shows
      that during the current time frame and with the present dose of Li+ in PLGA
      implants, Li+ is not an enhancer of early bone growth, although it affects the
      Wnt signaling pathway. 

PMID- 25047351
TI  - Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms
      of cyclosporin A-induced hepatotoxicity.
AB  - The liver is responsible for drug metabolism and drug-induced hepatotoxicity is
      the most frequent reason for drug withdrawal, indicating that better pre-clinical
      toxicity tests are needed. In order to bypass animal models for toxicity
      screening, we exposed primary mouse hepatocytes for exploring the prototypical
      hepatotoxicant cyclosporin A. To elucidate the mechanisms underlying cyclosporin
      A-induced hepatotoxicity, we analyzed expression levels of proteins, mRNAs,
      microRNAs and metabolites. Integrative analysis of transcriptomics and proteomics
      showed that protein disulfide isomerase family A, member 4 was up-regulated on
      both the protein level and mRNA level. This protein is involved in protein
      folding and secretion in the endoplasmic reticulum. Furthermore, the microRNA mmu
      miR-182-5p which is predicted to interact with the mRNA of this protein, was also
      differentially expressed, further emphasizing endoplasmic reticulum stress as
      important event in drug-induced toxicity. To further investigate the interaction
      between the significantly expressed proteins, a network was created including
      genes and microRNAs known to interact with these proteins and this network was
      used to visualize the experimental data. In total 6 clusters could be
      distinguished which appeared to be involved in several toxicity related
      processes, including alteration of protein folding and secretion in the
      endoplasmic reticulum. Metabonomic analyses resulted in 5 differentially
      expressed metabolites, indicative of an altered glucose, lipid and cholesterol
      homeostasis which can be related to cholestasis. Single and integrative analyses
      of transcriptomics, proteomics and metabonomics reveal mechanisms underlying
      cyclosporin A-induced cholestasis demonstrating that endoplasmic reticulum stress
      and the unfolded protein response are important processes in drug-induced liver
      toxicity. 

PMID- 25047352
TI  - Thermal cycling effects on adhesion of resin-bovine enamel junction among
      different composite resins.
AB  - Thermal cycling is used to mimic the changes in oral cavity temperature
      experienced by composite resins when used clinically. The purpose of this study
      is to assess the thermal cycling effects of in-house produced composite resin on
      bonding strength. The dicalcium phosphate anhydrous filler surfaces are modified
      using nanocrystals and silanization (w/NP/Si). The resin is compared with
      commercially available composite resins Filtek Z250, Z350, and glass ionomer
      restorative material GIC Fuji-II LC (control). Different composite resins were
      filled into the dental enamel of bovine teeth. The bond force and resin-enamel
      junction graphical structures of the samples were determined after thermal
      cycling between 5 and 55 degrees C in deionized water for 600 cycles. After
      thermal cycling, the w/NP/Si 30wt%, 50wt% and Filtek Z250, Z350 groups showed
      higher shear forces than glass ionomer GIC, and w/NP/Si 50wt% had the highest
      shear force. Through SEM observations, more of the fillings with w/NP/Si 30wt%
      and w/NP/Si 50wt% groups flowed into the enamel tubule, forming closed tubules
      with the composite resins. The push-out force is proportional to the resin flow
      depth and uniformity. The push-out tubule pore and resin shear pattern is the
      most uniform and consistent in the w/NP/Si 50wt% group. Accordingly, this
      developed composite resin maintains great mechanical properties after thermal
      cycling. Thus, it has the potential to be used in a clinical setting when
      restoring non-carious cervical lesions. 

PMID- 25047353
TI  - Microscopic contact area and friction between medical textiles and skin.
AB  - The mechanical contact between medical textiles and skin is relevant in the
      health care for patients with vulnerable skin or chronic wounds. In order to gain
      new insights into the skin-textile contact on the microscopic level, the 3D
      surface topography of a normal and a new hospital bed sheet with a regular
      surface structure was measured using a digital microscope. The topographic data
      was analysed concerning material distribution and real contact area against
      smooth surfaces as a function of surface deformations. For contact conditions
      that are relevant for the skin of patients lying in a hospital bed it was found
      that the order of magnitude of the ratio of real and apparent contact area
      between textiles and skin or a mechanical skin model lies between 0.02 and 0.1
      and that surface deformations, i.e. penetration of the textile surface asperities
      into skin or a mechanical skin model, range from 10 to 50um. The performed
      analyses of textile 3D surface topographies and comparisons with previous
      friction measurement results provided information on the relationship between
      microscopic surface properties and macroscopic friction behaviour of medical
      textiles. In particular, the new bed sheet was found to be characterised by a
      trend towards a smaller microscopic contact area (up to a factor of two) and by a
      larger free interfacial volume (more than a factor of two) in addition to a 1.5
      times lower shear strength when in contact with counter-surfaces. The applied
      methods can be useful to develop improved and skin-adapted materials and surfaces
      for medical applications. 

PMID- 25047354
TI  - Fluctuation between fasting and 2-H postload glucose state is associated with
      chronic kidney disease in previously diagnosed type 2 diabetes patients with
      HbA1c >= 7%.
AB  - OBJECTIVE: To investigate how the glucose variability between fasting and a 2-h
      postload glucose state (2-h postload plasma glucose [2hPG]-fasting plasma glucose
      [FPG]) is associated with chronic kidney disease (CKD) in middle-aged and elderly
      Chinese patients previously diagnosed with type 2 diabetes. DESIGN AND METHODS:
      This cross-sectional study included 1054 previously diagnosed type 2 diabetes
      patients who were 40 years of age and older. First, the subjects were divided
      into two groups based on a glycated hemoglobin (HbA1c) value of 7%. Each group
      was divided into two subgroups, with or without CKD. The Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) equation was used to estimate the glomerular
      filtration rate (GFR). CKD was defined as eGFR<60 mL/min/1.73 m2. Multiple linear
      regression analysis was used to estimate the association between the 2hPG-FPG and
      eGFR. The 2hPG-FPG value was divided into four groups increasing in increments of
      36 mg/dl (2.0 mmol/L): 0-72, 72-108, 108-144 and >=144 mg/dl, based on the
      quartiles of patients with HbA1c levels >=7%; then, binary logistic regression
      analysis was used to investigate the association between 2hPG-FPG and the risk of
      CKD. RESULTS: In the patients with HbA1c levels >=7%, the 2hPG-FPG was
      significantly associated with decreased eGFR and an increased risk of CKD
      independent of age, gender, body mass index (BMI), systolic blood pressure (BP),
      diastolic BP, smoking, and drinking, as well as fasting insulin, cholesterol,
      triglyceride, and HbA1c levels. The patients with 2hPG-FPG values >=144 mg/dl
      showed an increased odds ratio (OR) of 2.640 (P = 0.033). Additionally, HbA1c was
      associated with an increased risk of CKD in patients with HbA1c values >=7%.
      CONCLUSIONS: The short-term glucose variability expressed by 2hPG-FPG is closely
      associated with decreased eGFR and an increased risk of CKD in patients with poor
      glycemic control (HbA1c>=7%).

PMID- 25047355
TI  - Microglial displacement of inhibitory synapses provides neuroprotection in the
      adult brain.
AB  - Microglia actively survey the brain microenvironment and play essential roles in
      sculpting synaptic connections during brain development. While microglial
      functions in the adult brain are less clear, activated microglia can closely
      appose neuronal cell bodies and displace axosomatic presynaptic terminals.
      Microglia-mediated stripping of presynaptic terminals is considered
      neuroprotective, but the cellular and molecular mechanisms are poorly defined.
      Using 3D electron microscopy, we demonstrate that activated microglia displace
      inhibitory presynaptic terminals from cortical neurons in adult mice.
      Electrophysiological recordings further establish that the reduction in
      inhibitory GABAergic synapses increased synchronized firing of cortical neurons
      in gamma-frequency band. Increased neuronal activity results in the calcium
      mediated activation of CaM kinase IV, phosphorylation of CREB, increased
      expression of antiapoptotic and neurotrophic molecules and reduced apoptosis of
      cortical neurons following injury. These results indicate that activated
      microglia can protect the adult brain by migrating to inhibitory synapses and
      displacing them from cortical neurons. 

PMID- 25047356
TI  - Oxidative enzymatic response of white-rot fungi to single-walled carbon
      nanotubes.
AB  - Although carbon nanomaterials such as single-walled carbon nanotubes (SWCNT) are
      becoming increasingly prevalent in manufacturing, there is little knowledge on
      the environmental fate of these materials. Environmental degradation of SWCNT is
      hindered by their highly condensed aromatic structure as well as the size and
      aspect ratio, which prevents intracellular degradation and limits microbial
      decomposition to extracellular processes such as those catalyzed by oxidative
      enzymes. This study investigates the peroxidase and laccase enzymatic response of
      the saprotrophic white-rot fungi Trametes versicolor and Phlebia tremellosa when
      exposed to SWCNTs of different purity and surface chemistry under different
      growth conditions. Both unpurified, metal catalyst-rich SWCNT and purified,
      carboxylated SWCNTs promoted significant changes in the oxidative enzyme activity
      of the fungi while pristine SWCNT did not. These results suggest that
      functionalization of purified SWCNT is essential to up regulate enzymes that may
      be capable of decomposing CNT in the environment. 

PMID- 25047357
TI  - Isolation of mast cells from the peritoneal exudate of the teleost fish gilthead
      sea bream (Sparus aurata L.).
AB  - Inflammation is the first response of animals to infection or tissue damage.
      Sparus aurata (Perciformes) was the first fish species shown to possess histamine
      containing mast cells at mucosal tissues. We report a separation protocol for
      obtaining highly enriched (over 95% purity) preparations of fish mast cells in
      high numbers (5-20 million mast cells per fish). The peritoneal exudate of S.
      aurata is composed of lymphocytes, acidophilic granulocytes, macrophages and mast
      cells. We separated the lymphocyte fraction through discontinuous density
      gradient centrifugation. The remaining cells were cultivated overnight in RPMI
      1640 culture medium containing 5% fetal calf serum, which allowed macrophages to
      adhere to the cell culture flasks. Finally, acidophilic granulocytes were
      separated from the mast cells though a Magnetic-Activated Cell Separation (MACS)
      protocol, using a monoclonal antibody against these cells. The purity of mast
      cells-enriched fractions was analyzed by flow cytometry and by transmission
      electron microscopy. The functionality of purified mast cells was confirmed by
      the detection of histamine release by ELISA after stimulation with compound 48/80
      and the induction of the pro-inflammatory cytokines IL-1beta and IL-8 following
      stimulation with bacterial DNA. This fish mast cells separation protocol is a
      stepping stone for further studies addressing the evolution of vertebrate
      inflammatory mechanisms. 

PMID- 25047358
TI  - Induction of brown cells in Venerupis philippinarum exposed to benzo(a)pyrene.
AB  - Benzo(a)pyrene is an important polycyclic aromatic hydrocarbon (PAH) commonly
      present in the marine environment and responsible for carcinogenic, teratogenic
      and mutagenic effects in various animal species. In the present study, we
      investigated by both histochemical and immunohistochemical approaches the effect
      of an acute exposure to different concentrations of B(a)P in the Manila clam
      Venerupis philippinarum. The general morphology of the different clam tissues,
      which was investigated histologically, evidenced a significant increase in the
      number of intestinal brown cells after B(a)P exposure. An increasing trend
      response to B(a)P was detected. The histochemical analysis for lipofuscin
      revealed the presence of lipofuscin-like substances inside the cytoplasm of
      intestinal brown cells. The same cells exhibited a PAS positivity and a
      reactivity to Schmorl's solution for melanin pigment. Moreover, intestinal brown
      cells exhibited an immunopositivity to HSP70 antibody confirming the increasing
      trend response to B(a)P detected by the histochemical analysis. Our results
      suggest that histological tissue changes resulting from exposure to B(a)P can be
      an useful marker in biomonitoring studies. 

PMID- 25047359
TI  - Dietary tryptophan modulates intestinal immune response, barrier function,
      antioxidant status and gene expression of TOR and Nrf2 in young grass carp
      (Ctenopharyngodon idella).
AB  - The present research evaluated the effects of dietary tryptophan (Trp) on growth
      performance, intestinal mucosal immune, barrier function and antioxidant capacity
      and gene expression of young grass carp (Ctenopharyngodon idella). Fish were fed
      six different experimental diets containing graded levels of Trp at 0.7(control),
      1.7, 3.1, 4.0, 5.2 and 6.1 g kg(-1) diet for 8 weeks. The results showed that Trp
      supplementation significantly enhanced the percent weight gain (PWG), feed intake
      and feed efficiency (P < 0.05), and decreased the plasma ammonia content (PAC) (P
      < 0.05). After the 8-week feeding trail, an environmental copper exposure trail
      was conducted for 4 days. Results from the copper exposure trail showed that
      dietary Trp enhanced the lysozyme, acid phosphatase activities and complement 3
      contents in the intestine of young grass carp (P < 0.05). In addition, Trp
      supplementation increased the copper/zinc superoxide dismutase (SOD1),
      glutathione peroxidase (GPx) activities and glutathione contents (P < 0.05), and
      decreased the protein carbonyl and malondialdehyde contents (P < 0.05).
      Furthermore, the relative gene expression levels of interleukin 10, transforming
      growth factor-beta1, occludin, zonula occludens 1, claudin-b, -c, and -3, SOD1,
      GPx and NF-E2-related factor 2 in the intestine were significantly up-regulated
      with increasing of dietary Trp up to a certain level (P < 0.05). Conversely, the
      mRNA levels of tumor necrosis factor alpha, interleukin 8, target of rapamycin,
      Kelch-like-ECH-associated protein 1, claudin-12 and -15a in the intestine were
      significantly down-regulated by Trp (P < 0.05). Collectively, appropriate dietary
      Trp level improves fish growth, intestinal immune response, barrier function and
      antioxidant status, and regulated the mRNA levels of related signal molecules of
      young grass carp. Based on the quadratic regression analysis of the PWG and PAC,
      the dietary Trp requirement of young grass carp (287-699 g) was estimated to be
      3.81 g kg(-1) diet (12.7 g kg(-1) protein) and 3.89 g kg(-1) diet (13.0 g kg(-1)
      protein), respectively.

PMID- 25047360
TI  - Nondestructive methods for recovery of biological material from human teeth for
      DNA extraction.
AB  - The extraction of DNA from human skeletal remains applied to forensic, and
      evolutionary studies do not exclude risks, which are to be evaluated when working
      with unique specimens that could be damaged or even destroyed. In the present
      study were evaluated several nondestructive methods for recovering DNA instead of
      the most currently used pulverization method. Three different procedures to
      access inside the dental pieces (occlusal perforation, cervical perforation, and
      cervical cut) have been compared with the aim of recovering as many cell remains
      as possible to carry out a DNA extraction. Given the DNA quantitation results, a
      method was proposed that consists of a cervical cut to facilitate the access to
      the pulp cavity and a subsequent filing of the root canals down to the apex of
      the dental root. This methodology allows the recovery of both mitochondrial and
      nuclear DNA, with the minimum deterioration for the dental pieces. 

PMID- 25047361
TI  - Impact of energy loss index and valvuloarterial impedance in patients with aortic
      stenosis using three-dimensional echocardiography.
AB  - BACKGROUND: Energy loss index (ELI) and valvuloarterial impedance (Z(va)) have
      been evaluated with a lack of three-dimensional (3D) information regarding the
      left ventricular outflow tract (LVOT) and sino-tubular junction (STJ). Our aim of
      this study is to compare the difference of ELI and Z(va) between two-dimensional
      (2D) and 3D echocardiography. METHODS: In 74 patients with moderate-to-severe
      aortic stenosis, the effective orifice area index (EOAI: EOA/body surface area)
      was calculated by continuity equation based on both 2D transthoracic
      echocardiography (2DTTE) and 3D transesophageal echocardiography (3DTEE). The
      areas of the LVOT and the STJ were calculated with the assumption of pi *
      (dimension/2)(2) by 2DTTE and were measured directly by 3DTEE. Severe AS was
      defined as EOAI or ELI <0.6 cm(2) /m(2) or Z(va) >= 4.5 mmHg/mL per m(2) .
      RESULTS: Both the LVOT and STJ were elliptical, and LVOT was more elliptical than
      STJ. The ELI by 3DTEE (0.58 cm(2) /m(2) [median]) was larger than the other 3
      values: EOAI on 2DTTE = 0.41, P < 0.01; EOAI on 3DTEE = 0.49, P < 0.01; and ELI
      on 2DTTE = 0.49, P < 0.01. Furthermore, Z(va) by 2DTTE, 4.7 mmHg/mL per m(2), was
      larger than that by 3DTEE (3.8, P < 0.01). CONCLUSIONS: 2DTTE underestimated EOAI
      and ELI relative to 3DTEE and overestimated Z(va) relative to 3DTEE.

PMID- 25047362
TI  - Breast cancer risk in young women in the national breast screening programme:
      implications for applying NICE guidelines for additional screening and
      chemoprevention.
AB  - In the United Kingdom, women at moderate and high risk of breast cancer between
      the ages of 40 and 49 years are eligible for annual mammographic screening and
      preventive therapy with tamoxifen. Here, we estimate the numbers of women in a
      population eligible for this service and the proportion of breast cancers
      detected in this group compared with the whole population. Women <50 attending
      for mammographic screening in the National Health Service Breast Screening
      Programme (NHSBSP) completed a risk questionnaire. The proportion at moderate and
      high risk according to National Institute of Health Care Excellence (NICE)
      guidelines was estimated. An estimate was also made using a different model of
      risk estimation (Tyrer-Cuzick). The numbers of cancers detected in the
      moderate/high risk groups were compared with numbers detected in the whole
      population. Completed questionnaires were available for 4,360 women between ages
      46 and 49 years. Thirty women [0.7%; 95% confidence interval (CI), 0.5-1.0%] were
      at high risk and 130 (3.0%, 2.5-3.5%) were at moderate risk according to NICE
      guidelines. Thirty-seven cancers were detected by mammography in the whole group.
      Five of these were found in the moderate-/high-risk group giving a 3.2-fold
      increase in detection compared with the standard risk group. More women were
      assigned to the moderate- or high-risk group using the Tyrer-Cuzick model (N =
      384), but the numbers of cancers in this group were not appreciably increased (N
      = 8). Systematic assessment of family history in primary care or through
      population-based screening will identify appreciable numbers of women in their
      forties, eligible for additional surveillance and chemoprevention.

PMID- 25047363
TI  - Impact of wait times on the effectiveness of transcatheter aortic valve
      replacement in severe aortic valve disease: a discrete event simulation model.
AB  - BACKGROUND: There is increasing demand for transcatheter aortic valve replacement
      (TAVR) as the primary treatment option for patients with severe aortic stenosis
      who are high-risk surgical candidates or inoperable. We used mathematical
      simulation models to estimate the hypothetical effectiveness of TAVR with
      increasing wait times. METHODS: We applied discrete event modelling, using data
      from the Placement of Aortic Transcatheter Valves (PARTNER) trials. We compared
      TAVR with medical therapy in the inoperable cohort, and compared TAVR to
      conventional aortic valve surgery in the high-risk cohort. One-year mortality and
      wait-time deaths were calculated in different scenarios by varying TAVR wait
      times from 10 days to 180 days, while maintaining a constant wait time for
      surgery at a mean of 15.6 days. RESULTS: In the inoperable cohort, the 1-year
      mortality for medical therapy was 50%. When the TAVR wait time was 10 days, the
      TAVR wait-time mortality was 1.9% with a 1-year mortality of 31.5%. TAVR wait
      time deaths increased to 28.9% with a 180-day wait, with a 1-year mortality of
      41.4%. In the high-risk cohort, the wait-time deaths and 1-year mortality for the
      surgical patients were 2.5% and 27%, respectively. The TAVR wait-time deaths
      increased from 2.2% with a 10-day wait to 22.4% with a 180-day wait, and a
      corresponding increase in 1-year mortality from 24.5% to 32.6%. Mortality with
      TAVR exceeded surgery when TAVR wait times exceeded 60 days. CONCLUSIONS: Modest
      increases in TAVR wait times have a substantial effect on the effectiveness of
      TAVR in inoperable patients and high-risk surgical candidates.

PMID- 25047364
TI  - Coordination-driven in situ self-assembly strategy for the preparation of metal
      organic framework hybrid membranes.
AB  - Metal-organic frameworks (MOFs) have emerged as porous solids of a superior type
      for the fabrication of membranes. However, it is still challenging to prepare a
      uniformly dispersed robust MOF hybrid membrane. Herein, we propose a simple and
      powerful strategy, namely, coordination-driven in situ self-assembly, for the
      fabrication of MOF hybrid membranes. On the basis of the coordination
      interactions between metal ions and ligands and/or the functional groups of the
      organic polymer, this method was confirmed to be feasible for the production of a
      stable membrane with greatly improved MOF-particle dispersion in and
      compatibility with the polymer, thus providing outstanding separation ability. As
      an experimental proof of concept, a high-quality ZIF-8/PSS membrane was
      fabricated that showed excellent performance in the nanofiltration and separation
      of dyes from water. 

PMID- 25047365
TI  - Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis.
AB  - BACKGROUND: The early detection of medullary thyroid carcinoma (MTC) can improve
      patient prognosis, because histological stage and patient age at diagnosis are
      highly relevant prognostic factors. As a consequence, delay in the diagnosis
      and/or incomplete surgical treatment should correlate with a poorer prognosis for
      patients. Few papers have evaluated the specific capability of fine-needle
      aspiration cytology (FNAC) to detect MTC, and small series have been reported.
      This study conducts a meta-analysis of published data on the diagnostic
      performance of FNAC in MTC to provide more robust estimates. RESEARCH DESIGN AND
      METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase
      and Scopus databases was conducted by searching for the terms 'medullary thyroid'
      AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search
      was updated until 21 March 2014, and no language restrictions were used. RESULTS:
      Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were
      included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as
      'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12.5%
      to 88.2%, with a pooled estimate of 56.4% (95% CI: 52.6-60.1%). The included
      studies were statistically heterogeneous in their estimates of DR (I-square
      >50%). Egger's regression intercept for DR pooling was 0.03 (95% CI: -3.1 to 3.2,
      P = 0.9). The study that reported the largest MTC series had a DR of 45%. Data on
      immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the
      meta-analysis. CONCLUSIONS: The presented meta-analysis demonstrates that FNAC is
      able to detect approximately one-half of MTC lesions. These findings suggest that
      other techniques may be needed in combination with FNAC to diagnose MTC and avoid
      false negative results.

PMID- 25047366
TI  - De novo assembly, gene annotation, and simple sequence repeat marker development
      using Illumina paired-end transcriptome sequences in the pearl oyster Pinctada
      maxima.
AB  - We analyzed the mantle transcriptome of pearl oyster Pinctada maxima and
      developed EST-SSR markers using Illumina HiSeq 2000 paired-end sequencing
      technology. A total of 49,500,748 raw reads were generated. De novo assembly
      generated 108,704 unigenes with an average length of 407 bp. Sequence similarity
      search with known proteins or nucleotides revealed that 30,200 (27.78%) and
      25,824 (23.76%) consensus sequences were homologous with the sequences in the non
      redundant protein and Swiss-Prot databases, respectively, and that 19,701
      (18.12%) of these unigenes were possibly involved in approximately 234 known
      signaling pathways in the Kyoto Encyclopedia of Genes and Genomes database.
      Ninety one biomineralization-related unigenes were detected. In a cultured stock,
      1764 simple sequence repeats were identified and 56 primer pairs were randomly
      selected and tested. The rate of successful amplification was 68.3%. The
      developed molecular markers are helpful for further studies on genetic linkage
      analysis, gene localization, and quantitative trait loci mapping.

PMID- 25047367
TI  - Early maternal depressive symptoms and child growth trajectories: a longitudinal
      analysis of a nationally representative US birth cohort.
AB  - BACKGROUND: Maternal depressive symptoms are negatively associated with early
      child growth in developing countries; however, few studies have examined this
      relation in developed countries or used a longitudinal design with data past the
      second year of the child's life. We investigated if and when early maternal
      depressive symptoms affect average growth in young children up to age 6 in a
      nationally representative sample of US children. METHODS: Using data from 6,550
      singleton births from the Early Childhood Longitudinal Study -- Birth Cohort
      (ECLS-B), we fit growth trajectory models with random effects to examine the
      relation between maternal depressive symptoms at 9 months based on the twelve
      item version of the Center for Epidemiologic Studies Depression Scale (CES-D) and
      child height and body mass index (BMI) to age 6 years. RESULTS: Mothers with
      moderate/severe depressive symptoms at 9 months postpartum had children with
      shorter stature at this same point in time [average 0.26 cm shorter; 95% CI: 5
      cm, 48 cm] than mothers without depressive symptoms; children whose mothers
      reported postpartum depressive symptoms remained significantly shorter throughout
      the child's first 6 years. CONCLUSIONS: Results suggest that the first year
      postpartum is a critical window for addressing maternal depressive symptoms in
      order to optimize child growth. Future studies should investigate the role of
      caregiving and feeding practices as potential mechanisms linking maternal
      depressive symptoms and child growth trajectories.

PMID- 25047368
TI  - Positron emission tomography/magnetic resonance imaging with 68Gallium-labeled
      ligand of prostate-specific membrane antigen: promising novel option in prostate
      cancer imaging?

PMID- 25047369
TI  - Detection of olfactory dysfunction using olfactory event related potentials in
      young patients with multiple sclerosis.
AB  - BACKGROUND: Several studies reported olfactory dysfunction in patients with
      multiple sclerosis. The estimate of the incidence of olfactory deficits in
      multiple sclerosis is uncertain; this may arise from different testing methods
      that may be influenced by patients' response bias and clinical, demographic and
      cognitive features. AIMS: To evaluate objectively the olfactory function using
      Olfactory Event Related Potentials. MATERIALS AND METHODS: We tested the
      olfactory function of 30 patients with relapsing remitting multiple sclerosis
      (mean age of 36.03+/-6.96 years) and of 30 age, sex and smoking-habit matched
      healthy controls by using olfactory potentials. A selective and controlled
      stimulation of the olfactory system to elicit the olfactory event related
      potentials was achieved by a computer-controlled olfactometer linked directly
      with electroencephalograph. Relationships between olfactory potential results and
      patients' clinical characteristics, such as gender, disability status score,
      disease-modifying therapy, and disease duration, were evaluated. RESULTS: Seven
      of 30 patients did not show olfactory event related potentials. Sixteen of
      remaining 23 patients had a mean value of amplitude significantly lower than
      control group (p<0.01). The presence/absence of olfactory event related
      potentials was associated with dichotomous expanded disability status scale (p =
      0.0433), as well as inversely correlated with the disease duration (r = -0.3641,
      p = 0.0479). CONCLUSION: Unbiased olfactory dysfunction of different severity
      found in multiple sclerosis patients suggests an organic impairment which could
      be related to neuroinflammatory and/or neurodegenerative processes of olfactory
      networks, supporting the recent findings on neurophysiopathology of disease.

PMID- 25047371
TI  - Changing relative contribution of abdominal obesity and a family history of
      diabetes on prevalence of diabetes mellitus in Korean men and women aged 30-49
      years from 2001 to 2010.
AB  - BACKGROUND: We investigated the change in the relative impact of a family history
      of diabetes (FH) and abdominal obesity on diabetes mellitus (DM) over a 10-year
      period in Korea. METHODS: We analyzed data from the 2001, 2005, and 2010 Korean
      National Health and Nutrition Examination Survey that were weighted to represent
      the entire Korean population in each year. Multiple logistic regression analysis
      was used to examine the association between DM and FH or abdominal obesity.
      RESULTS: In men aged 30-49 years, the association between FH and DM was stronger
      in 2010 than in 2001; the odds ratio (OR) was 1.508 (95% confidence interval
      [CI], 0.814-2.792) in 2001, 3.351 (95% CI, 1.599-7.024) in 2005, and 7.302 (95%
      CI, 3.451-15.451) in 2010 (P for trend = 0.003). In contrast, the association
      between abdominal obesity and DM was weaker in 2010 (OR, 0.969 [95% CI, 0.465
      2.018]) than in 2001 (OR, 2.532 [95% CI, 1.572-4.080]) (P for trend = 0.037). In
      women aged 30-49 years, there was no significant change in OR of FH or abdominal
      obesity during the same period. (P for trend = 0.367 and 0.401, respectively).
      CONCLUSIONS: In Korean men aged 30-49 years, the association between FH and DM
      has been stronger from 2001 to 2010, whereas abdominal obesity was less important
      in 2010 compared to 2001.

PMID- 25047370
TI  - Intracellular lipid accumulation and shift during diabetes progression.
AB  - In past decades, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver
      disease developed into a global public health disease with an endemic scale.
      Although up to now the pathogenesis of T2DM is still poorly understood, ectopic
      lipid accumulation is one of the strongest predictors for T2DM and is closely
      associated with insulin resistance.This review aims (i) to overview recent
      literature on the impact of intracellular lipid deposition, (ii) to point out
      changes in ectopic fat accumulation during diabetes progression or shortly after
      initializing individual therapy, and finally (iii) to expose unsolved questions
      and future perspectives in the role of ectopic lipids for the development of
      insulin resistance and T2DM. 

PMID- 25047372
TI  - Developing hypothetical inhibition mechanism of novel urea transporter B
      inhibitor.
AB  - Urea transporter B (UT-B) is a membrane channel protein that specifically
      transports urea. UT-B null mouse exhibited urea selective urine concentrating
      ability deficiency, which suggests the potential clinical applications of the UT
      B inhibitors as novel diuretics. Primary high-throughput virtual screening (HTVS)
      of 50000 small-molecular drug-like compounds identified 2319 hit compounds. These
      2319 compounds were screened by high-throughput screening using an erythrocyte
      osmotic lysis assay. Based on the pharmacological data, putative UT-B binding
      sites were identified by structure-based drug design and validated by ligand
      based and QSAR model. Additionally, UT-B structural and functional
      characteristics under inhibitors treated and untreated conditions were simulated
      by molecular dynamics (MD). As the result, we identified four classes of
      compounds with UT-B inhibitory activity and predicted a human UT-B model, based
      on which computative binding sites were identified and validated. A novel
      potential mechanism of UT-B inhibitory activity was discovered by comparing UT-B
      from different species. Results suggest residue PHE198 in rat and mouse UT-B
      might block the inhibitor migration pathway. Inhibitory mechanisms of UT-B
      inhibitors and the functions of key residues in UT-B were proposed. The binding
      site analysis provides a structural basis for lead identification and
      optimization of UT-B inhibitors. 

PMID- 25047373
TI  - Methodological procedures followed in a kindergarten-based, family-involved
      intervention implemented in six European countries to prevent obesity in early
      childhood: the ToyBox-study.

PMID- 25047374
TI  - Designing and implementing a kindergarten-based, family-involved intervention to
      prevent obesity in early childhood: the ToyBox-study.
AB  - The development of the ToyBox-intervention was based on the outcomes of the
      preliminary phase of the ToyBox-study, aiming to identify young children's key
      behaviours and their determinants related to early childhood obesity. The ToyBox
      intervention is a multi-component, kindergarten-based, family-involved
      intervention with a cluster-randomized design, focusing on the promotion of water
      consumption, healthy snacking, physical activity and the reduction/ breaking up
      of sedentary time in preschool children and their families. The intervention was
      implemented during the academic year 2012-2013 in six European countries:
      Belgium, Bulgaria, Germany, Greece, Poland and Spain. Standardized protocols,
      methods, tools and material were used in all countries for the implementation of
      the intervention, as well as for the process, impact, outcome evaluation and the
      assessment of its cost-effectiveness. A total sample of 7,056 preschool children
      and their parents/caregivers, stratified by socioeconomic level, provided data
      during baseline measurements and participated in the intervention. The results of
      the ToyBox-study are expected to provide a better insight on behaviours
      associated with early childhood obesity and their determinants and identify
      effective strategies for its prevention. The aim of the current paper is to
      describe the design of the ToyBox-intervention and present the characteristics of
      the study sample as assessed at baseline, prior to the implementation of the
      intervention. 

PMID- 25047375
TI  - Applying the Intervention Mapping protocol to develop a kindergarten-based,
      family-involved intervention to increase European preschool children's physical
      activity levels: the ToyBox-study.
AB  - Although sufficient physical activity is beneficial for preschoolers' health,
      activity levels in most preschoolers are low. As preschoolers spend a
      considerable amount of time at home and at kindergarten, interventions should
      target both environments to increase their activity levels. The aim of the
      current paper was to describe the six different steps of the Intervention Mapping
      protocol towards the systematic development and implementation of the physical
      activity component of the ToyBox-intervention. This intervention is a
      kindergarten-based, family-involved intervention implemented across six European
      countries. Based on the results of literature reviews and focus groups with
      parents/caregivers and kindergarten teachers, matrices of change objectives were
      created. Then, theory-based methods and practical strategies were selected to
      develop intervention materials at three different levels: (i) individual level
      (preschoolers); (ii) interpersonal level (parents/caregivers) and (iii)
      organizational level (teachers). This resulted in a standardized intervention
      with room for local and cultural adaptations in each participating country.
      Although the Intervention Mapping protocol is a time-consuming process, using
      this systematic approach may lead to an increase in intervention effectiveness.
      The presented matrices of change objectives are useful for future programme
      planners to develop and implement an intervention based on the Intervention
      Mapping protocol to increase physical activity levels in preschoolers. 

PMID- 25047376
TI  - Developing the intervention material to increase physical activity levels of
      European preschool children: the ToyBox-study.
AB  - Early childhood is an important period for adopting positive health-related
      behaviours. More than 95% of European preschool children attend kindergartens,
      making these settings ideal for the implementation of health promotion
      interventions. The ToyBox-intervention addressed preschool children, their
      parents/caregivers and teachers. The aim of the intervention was to improve four
      energy balance-related behaviours (i.e. healthy snacking, water consumption,
      physical activity and sedentary behaviour) by implementing a kindergarten-based,
      family-involved intervention in six European countries (Belgium, Bulgaria,
      Germany, Greece, Poland and Spain). The intervention material was developed
      following the intervention mapping protocol, taking into account local and
      cultural differences among the intervention countries. The present paper focuses
      on the development of the physical activity component of the intervention.
      Parental involvement was addressed by providing parents/caregivers with two
      newsletters, two tip cards and a poster. Teachers received a handbook with
      guidance on environmental changes in the classroom, 26 physical education
      sessions and suggestions for fun, interactive classroom activities aiming at
      total class participation to increase preschoolers' physical activity levels. The
      ToyBox-intervention material was distributed according to a standard time frame.
      Teachers received their material prior to the start of the intervention and
      parents/caregivers received their material during the intervention when each
      energy balance-related behaviour was implemented. 

PMID- 25047378
TI  - Designing and implementing teachers' training sessions in a kindergarten-based,
      family-involved intervention to prevent obesity in early childhood. The ToyBox
      study.
AB  - Since school-based interventions are mainly delivered by the school staff, they
      need to be well-trained and familiarized with the programme's aims, procedures
      and tools. Therefore, the institute, research group, governmental or non
      governmental body in charge of the coordination and implementation of the
      programme needs to devote time and resources to train the school staff before
      programme's implementation. This is particularly crucial in multi-centre studies
      where more than one research teams are involved. Both research teams and school
      staff need to be trained, using standard protocols and procedures, to ensure that
      the intervention will be delivered in a standardized manner throughout the
      intervention centres. The ToyBox-intervention, a multi-component, kindergarten
      based, family-involved intervention, focusing on water consumption, snacking,
      physical activity and sedentary behaviours in preschool children, was implemented
      over the academic year 2012-2013 in six European countries. As part of this
      intervention, three teachers' training sessions were delivered to motivate and
      train teachers in implementing the intervention. The local researchers were
      trained centrally before delivering the training sessions for the teachers and
      followed a common protocol using standardized presentations and procedures. The
      aim of the current paper is to describe the protocol and methodological issues
      related to the teachers' training sessions conducted within the ToyBox
      intervention. 

PMID- 25047377
TI  - Concepts and strategies on how to train and motivate teachers to implement a
      kindergarten-based, family-involved intervention to prevent obesity in early
      childhood. The ToyBox-study.
AB  - The key person for the implementation of kindergarten-based behavioural
      interventions is the kindergarten teacher. When conducting intervention studies
      in kindergartens, training sessions are needed to train and motivate kindergarten
      teachers for programme implementation. This paper presents the systematic
      development of the teachers' trainings executed in the ToyBox-intervention - a
      kindergarten-based and family-involved obesity prevention programme for children
      aged 4-6. Based on concepts for the education of kindergarten teachers, on
      general strategies for successful programme implementation and on the ToyBox
      programme-specific requirements, the aims of the teachers' trainings were defined
      and an overall concept was deduced. Regarding the concept for the ToyBox
      teachers' training sessions, it is concluded that the training modules should
      focus on presenting information on the practical implementation of the
      intervention. Furthermore, these modules should also include self-efficacy
      enhancing components and should give kindergarten teachers opportunities to share
      experiences. Regarding the didactic methods applied in the ToyBox teachers'
      training sessions, constructivist learning approaches that facilitate active
      participation, reflective thinking and personal involvement were implemented.
      Emphasis was put not only on the content but especially on the didactic methods
      of teachers' trainings in order to enhance devotion to, and quality and
      sustainability of the ToyBox-intervention. 

PMID- 25047379
TI  - Tools, harmonization and standardization procedures of the impact and outcome
      evaluation indices obtained during a kindergarten-based, family-involved
      intervention to prevent obesity in early childhood: the ToyBox-study.
AB  - The ToyBox-intervention is a kindergarten-based, family-involved intervention
      targeting multiple lifestyle behaviours in preschool children, their teachers and
      their families. This intervention was conducted in six European countries, namely
      Belgium, Bulgaria, Germany, Greece, Poland and Spain. The aim of this paper is to
      provide a descriptive overview of the harmonization and standardization
      procedures of the baseline and follow-up evaluation of the study (and
      substudies). Steps related to the study's operational, standardization and
      harmonization procedures as well as the impact and outcome evaluation assessment
      tools used are presented. Experiences from the project highlight the importance
      of safeguarding the measurement process to minimize data heterogeneity derived
      from potential measurement error and country-by-country differences. In addition,
      it was made clear that continuing quality control and support is an important
      component of such studies. For this reason, well-supported communication
      channels, such as regular email updates and teleconferences, and regular internal
      and external meetings to ensure smooth and accurate implementation were in place
      during the study. The ToyBox-intervention and its harmonized and standardized
      procedures can serve as a successful case study for future studies evaluating the
      efficacy of similar interventions. 

PMID- 25047380
TI  - Reliability of primary caregivers reports on lifestyle behaviours of European pre
      school children: the ToyBox-study.
AB  - Reliable assessments of health-related behaviours are necessary for accurate
      evaluation on the efficiency of public health interventions. The aim of the
      current study was to examine the reliability of a self-administered primary
      caregivers questionnaire (PCQ) used in the ToyBox-intervention. The questionnaire
      consisted of six sections addressing sociodemographic and perinatal factors,
      water and beverages consumption, physical activity, snacking and sedentary
      behaviours. Parents/caregivers from six countries (Belgium, Bulgaria, Germany,
      Greece, Poland and Spain) were asked to complete the questionnaire twice within a
      2-week interval. A total of 93 questionnaires were collected. Test-retest
      reliability was assessed using intra-class correlation coefficient (ICC).
      Reliability of the six questionnaire sections was assessed. A stronger agreement
      was observed in the questions addressing sociodemographic and perinatal factors
      as opposed to questions addressing behaviours. Findings showed that 92% of the
      ToyBox PCQ had a moderate-to-excellent test-retest reliability (defined as ICC
      values from 0.41 to 1) and less than 8% poor test-retest reliability (ICC <
      0.40). Out of the total ICC values, 67% showed good-to-excellent reliability (ICC
      from 0.61 to 1). We conclude that the PCQ is a reliable tool to assess
      sociodemographic characteristics, perinatal factors and lifestyle behaviours of
      pre-school children and their families participating in the ToyBox-intervention. 

PMID- 25047381
TI  - Reliability of anthropometric measurements in European preschool children: the
      ToyBox-study.
AB  - The ToyBox-study aims to develop and test an innovative and evidence-based
      obesity prevention programme for preschoolers in six European countries: Belgium,
      Bulgaria, Germany, Greece, Poland and Spain. In multicentre studies,
      anthropometric measurements using standardized procedures that minimize errors in
      the data collection are essential to maximize reliability of measurements. The
      aim of this paper is to describe the standardization process and reliability
      (intra- and inter-observer) of height, weight and waist circumference (WC)
      measurements in preschoolers. All technical procedures and devices were
      standardized and centralized training was given to the fieldworkers. At least
      seven children per country participated in the intra- and inter-observer
      reliability testing. Intra-observer technical error ranged from 0.00 to 0.03 kg
      for weight and from 0.07 to 0.20 cm for height, with the overall reliability
      being above 99%. A second training was organized for WC due to low reliability
      observed in the first training. Intra-observer technical error for WC ranged from
      0.12 to 0.71 cm during the first training and from 0.05 to 1.11 cm during the
      second training, and reliability above 92% was achieved. Epidemiological surveys
      need standardized procedures and training of researchers to reduce measurement
      error. In the ToyBox-study, very good intra- and-inter-observer agreement was
      achieved for all anthropometric measurements performed. 

PMID- 25047382
TI  - Process evaluation design and tools used in a kindergarten-based, family-involved
      intervention to prevent obesity in early childhood. The ToyBox-study.
AB  - Process evaluation (PE) is used for the in-depth evaluation of the implementation
      process of health promotion programmes. The aim of the current paper was to
      present the PE design and tools used in the ToyBox-intervention. The PE design
      was based on a three-step approach, including the identification of ToyBox
      specific PE elements (step 1), the development of PE tools and harmonization of
      procedures (step 2), and the implementation of PE using standardized protocol and
      tools across the intervention countries (step 3). Specifically, to evaluate the
      implementation of the intervention, teachers' monthly logbooks were recorded
      (dose delivered, fidelity, dose received); post-intervention questionnaires were
      completed by parents/caregivers and teachers (dose received); participation and
      attrition rates were recorded (recruitment, reach); and audit questionnaires and
      retrospective information on weather conditions were collected (physical and
      social environment within which the intervention was implemented). Regarding the
      teachers' training sessions, the researchers who performed the trainings
      completed evaluation forms and documented teachers' attendance after each
      training (dose delivered, fidelity, dose received) and teachers completed
      evaluation forms after each training (dose received). The PE performed in the
      ToyBox-intervention may contribute in the evaluation of its effectiveness, guide
      the revision of the intervention material and provide insights for future health
      promotion programmes and public health policy. 

PMID- 25047384
TI  - T-bet modulates the antibody response and immune protection during murine
      malaria.
AB  - CD4(+) T-cell subtypes govern the synthesis of different Ab isotypes and other
      immune functions. The influence of CD4(+) T-cell differentiation programs on
      isotype switching and other aspects of host immunological networks during malaria
      infection are currently poorly understood. Here, we used Tbx21(-/-) mice
      deficient for T-bet, a regulator of Th1 CD4(+) T-cell differentiation, to examine
      the effect of Th1 CD4(+) T cells on the immune protection to nonlethal murine
      malaria Plasmodium yoelii 17XNL. We found that Tbx21(-/-) mice exhibited
      significantly lower parasite burden that correlated with elevated levels of IgG1,
      indicating that T-bet-dependent Ab isotype switching may be responsible for lower
      parasite burden. Absence of T-bet was also associated with a transient but
      significant loss of T cells during the infection, suggesting that T-bet may
      suppress malaria-induced apoptosis or induce proliferation of T cells. However,
      Tbx21(-/-) mice produced greater numbers of Foxp3(+) CD25(+) regulatory CD4(+) T
      cells, which may contribute to the early contraction of T cells. Lastly, Tbx21(-/
      ) mice exhibited unimpaired production of IFN-gamma by a diverse repertoire of
      immune cell subsets and a selective expansion of IFN-gamma-producing T cells.
      These observations may have implications in malaria vaccine design.

PMID- 25047385
TI  - Commentary on Ronen T, Hamama L and Rosenbaum M (2012) Enuresis--children's
      predictions of their treatment's progress and outcomes. Journal of Clinical
      Nursing 22, 222-232.

PMID- 25047383
TI  - Establishing a method to estimate the cost-effectiveness of a kindergarten-based,
      family-involved intervention to prevent obesity in early childhood. The ToyBox
      study.
AB  - Overweight and obesity in children are recognized as a major health problem. The
      ToyBox-intervention was developed with the aim of preventing obesity in pre
      schoolers. Because it is increasingly important to inform policy makers not only
      on the effects of prevention interventions, but also on their costs and cost
      effectiveness, our purpose was to establish a method to estimate the cost
      effectiveness of the ToyBox-intervention. In order to estimate the long-term
      impact of the ToyBox-intervention on health and societal costs, extrapolations of
      the intervention effect will be conducted to predict children's weight status
      (based on the body mass index) at adult age. Effects of the adult weight status
      on the prevalence of obesity-related complications will be modelled through a
      Markov model, with a total time horizon of 70 years and a cycle length of 1 year.
      The model will be conducted in six European countries participating in the ToyBox
      intervention, based on country-specific economic and epidemiological data. This
      study describes the methodological rationale and implementation of an analytic
      model to examine the cost-effectiveness of the ToyBox-intervention for six
      European countries, in order to inform decision-makers on the value for money of
      this intervention in the prevention of obesity in pre-schoolers. 

PMID- 25047386
TI  - Commentary on Fernandez R, Salamonson Y and Griffiths R (2012) Emotional
      intelligence as a predictor of academic performance in first-year accelerated
      graduate entry nursing students. Journal of Clinical Nursing 21, 3485-3492.

PMID- 25047387
TI  - Commentary on Cook C (2012) 'Nice girls don't': women and the condom conundrum.
      Journal of Clinical Nursing 21, 535-43.

PMID- 25047388
TI  - Commentary on Cone PH and Giske T (2013) Teaching spiritual care--a grounded
      theory study among nursing educators. Journal of Clinical Nursing 22, 1951-1960.

PMID- 25047389
TI  - Compromised endothelium-dependent hyperpolarization-mediated dilations can be
      rescued by NS309 in obese Zucker rats.
AB  - OBJECTIVE: NO and a non-NO/prostacyclin EDH mechanism are major contributors of
      vascular tone and cerebral blood flow. However, the effect of metabolic syndrome
      on EDH-mediated responses in cerebral vessels remains unknown and may offer
      another avenue for therapeutic targeting. The purpose of this study was to
      investigate EDH-dependent responses in cerebral arteries during metabolic
      syndrome. METHODS: EDH-dependent dilations were assessed in MCAs isolated from
      nondiabetic obese and lean Zucker rats in the presence and absence of NS309, an
      activator of SKCa and IKCa channels. IKCa channel expression and activity were
      assessed by western blotting and pressure myography, respectively. RESULTS: EDH
      mediated dilations were significantly attenuated in the obese compared to the
      lean Zucker rat MCA. Luminal delivery of 1 MUM NS309 enhanced EDH-mediated
      responses in lean and obese Zucker cerebral vessels. Both dose-dependent
      dilations to luminal NS309 and IKCa protein expression in pooled cerebral
      arteries were comparable between the two groups. CONCLUSIONS: Our results suggest
      that pharmacological targeting of IKCa channels can rescue EDH-mediated dilations
      in obese Zucker rat MCAs. Compromised EDH-mediated dilations in obesity are not
      due to impaired IKCa channel expression or activity.

PMID- 25047390
TI  - Methandiide as a non-innocent ligand in carbene complexes: from the electronic
      structure to bond activation reactions and cooperative catalysis.
AB  - The synthesis of a ruthenium carbene complex based on a sulfonyl-substituted
      methandiide and its application in bond activation reactions and cooperative
      catalysis is reported. In the complex, the metal-carbon interaction can be tuned
      between a Ru-C single bond with additional electrostatic interactions and a Ru=C
      double bond, thus allowing the control of the stability and reactivity of the
      complex. Hence, activation of polar and non-polar bonds (O-H, H-H) as well as
      dehydrogenation reactions become possible. In these reactions the carbene acts as
      a non-innocent ligand supporting the bond activation as nucleophilic center in
      the 1,2-addition across the metal-carbon double bond. This metal-ligand
      cooperativity can be applied in the catalytic transfer hydrogenation for the
      reduction of ketones. This concept opens new ways for the application of carbene
      complexes in catalysis.

PMID- 25047392
TI  - Top-down patterning and self-assembly for regular arrays of semiconducting single
      walled carbon nanotubes.
AB  - Highly pure semiconducting single-walled carbon nanotubes (SWNTs), sorted by
      density-gradient ultracentrifugation, undergo self-assembly using depletion
      attraction forces into rafts along lithographically defined patterns of narrow
      pitch (100 or 200 nm). The arrays demonstrate high pattern fidelity and channel
      filling, along with large-scale homogeneity. Field-effect transistors made from
      these arrays exhibit high performance at on/off ratios>1000.

PMID- 25047391
TI  - Qualifying unmet needs and improving standards of care in psoriatic arthritis.

PMID- 25047393
TI  - A systematic review of approaches for engaging patients for research on rare
      diseases.
AB  - BACKGROUND: Patients with rare diseases have limited access to useful information
      to guide treatment decisions. Engagement of patients and other stakeholders in
      clinical research may help to ensure that research efforts in rare diseases
      address relevant clinical questions and patient-centered health outcomes. Rare
      disease organizations may provide an effective means to facilitate patient
      engagement in research. However, the effectiveness of patient-engagement
      approaches, particularly for the study of rare diseases, has not been well
      studied. OBJECTIVES: To synthesize evidence about engagement of patients and
      other stakeholders in research on rare diseases, including the role of rare
      disease organizations in facilitating patient-centered research. METHODS/RESEARCH
      DESIGN: A systematic review and gray literature search were guided by a technical
      expert panel composed of patient representatives, clinicians, and researchers.
      English-language studies that engaged patients or other stakeholders in research
      on rare diseases or evaluated engagement were included. Studies were assessed on
      how well key research questions were answered, based on the level of detail
      describing engagement activities and whether outcomes from engagement were
      assessed. RESULTS: Thirty-five studies were included, although many reported
      minimal information on engagement. Patients and other stakeholders were most
      commonly engaged to identify patient-centered research agendas, to select which
      study outcomes were important to patients, to provide input on study design, and
      to identify strategies for increasing enrollment in trials. Rare disease
      organizations mainly helped provide access to patients and communicated research
      opportunities and findings. They also helped promote collaborative networks and
      provided financial support for research infrastructures. Although authors
      reported benefits of engagement and identified changes to their research
      processes, no empirical assessments of engagement practices and their
      effectiveness were found. CONCLUSIONS: Researchers studying rare diseases can
      obtain patient input regarding which research questions and health outcomes to
      study; however, the most effective approaches to engagement have not been well
      defined.

PMID- 25047394
TI  - Ciprofloxacin-induced tendinopathy of the gluteal tendons.
AB  - Fluoroquinolone-induced tendinopathy most commonly affects the Achilles tendon;
      however, involvement of several other tendons has been described. This is a case
      report of ciprofloxacin-induced tendinopathy of the gluteal tendons with MRI
      findings. An obese 25-year-old woman with no significant past medical history was
      diagnosed with acute pyelonephritis and was treated with intravenous
      ciprofloxacin. Shortly after her first dose of ciprofloxacin, she developed
      severe left hip pain and decreased range of motion. MRI of the hips showed
      bilateral tendinopathy of the gluteal muscle insertion. A diagnosis of
      ciprofloxacin-induced tendinopathy was made based on her MRI and a Naranjo score
      of 7. Ciprofloxacin was stopped and her pain quickly resolved. Fluoroquinolones
      cause tendinopathy in 0.14 % to 0.4 % of patients using these agents.
      Fluoroquinolone-associated tendinopathy is a serious adverse reaction that can
      affect many tendons and should be considered in any patient presenting with new
      musculoskeletal complaints and in whom there is a history of fluoroquinolone use
      within the preceding 6 months.

PMID- 25047395
TI  - Proteomics of rice and Cochliobolus miyabeanus fungal interaction: insight into
      proteins at intracellular and extracellular spaces.
AB  - Necrotrophic fungal pathogen Cochliobolus miyabeanus causes brown spot disease in
      rice leaves upon infection, resulting in critical rice yield loss. To better
      understand the rice-C. miyabeanus interaction, we employed proteomic approaches
      to establish differential proteomes of total and secreted proteins from the
      inoculated leaves. The 2DE approach after PEG-fractionation of total proteins
      coupled with MS (MALDI-TOF/TOF and nESI-LC-MS/MS) analyses led to identification
      of 49 unique proteins out of 63 differential spots. SDS-PAGE in combination with
      nESI-LC-MS/MS shotgun approach was applied to identify secreted proteins in the
      leaf apoplast upon infection and resulted in cataloging of 501 unique proteins,
      of which 470 and 31 proteins were secreted from rice and C. miyabeanus,
      respectively. Proteins mapped onto metabolic pathways implied their reprogramming
      upon infection. The enzymes involved in Calvin cycle and glycolysis decreased in
      their protein abundance, whereas enzymes in the TCA cycle, amino acids, and
      ethylene biosynthesis increased. Differential proteomes also generated
      distribution of identified proteins in the intracellular and extracellular
      spaces, providing a better insight into defense responses of proteins in rice
      against C. miyabeanus. Established proteome of the rice-C. miyabeanus interaction
      serves not only as a good resource for the scientific community but also
      highlights its significance from biological aspects. 

PMID- 25047396
TI  - The role of vitamin D in gastrointestinal inflammation.
AB  - The emerging role of vitamin D as a regulator of both innate and adaptive immune
      responses has encouraged the investigation of its role in the pathogenesis of a
      variety of autoimmune conditions including the inflammatory bowel diseases (IBD),
      Crohn's disease and ulcerative colitis. Animal models consistently demonstrate
      that vitamin D significantly impacts on the modulation of astrointestinal
      inflammation, while epidemiological and observational data show an inverse
      relationship between vitamin D status and the onset/progression of Crohn's
      disease as well as the development of colorectal cancer. As vitamin D
      supplementation is readily available, at low cost, it is a very attractive
      potential therapeutic option. The biological plausibility for a role for vitamin
      D in inflammation modulation, the potential genetic links associated with vitamin
      D metabolism and the clinical aspects for it in IBD will be discussed. 

PMID- 25047397
TI  - 'What will I be like' after my diagnosis of head and neck cancer?
AB  - Consequences of treating head and neck cancer are reflected in health-related
      quality of life (HRQOL) patient-reported outcomes. HRQOL is an important outcome
      alongside survival and recurrence. However, relatively little HRQOL information
      is in a format that patients and oncology teams can easily interpret as a guide
      to likely outcomes following curative treatment. The study aim was to collate
      University of Washington Quality of Life (UW-QOL) questionnaires collected 1995
      2012 at the Regional Head and Neck Surgical Unit with a view of summarizing key
      clinical-demographic influences on HRQOL outcomes at 2 years following diagnosis.
      Patients completing UW-QOL questionnaires at 9-60 months had their record closest
      to 2 years selected for cross-sectional analyses, while all questionnaires were
      analyzed to assess temporal trends. 65 % (1,134) of survivors to 9 months had a
      UW-QOL record in the cross-sectional analysis (median 23 months). Overall 1,349
      completed 5,573 UW-QOL questionnaires. Various associations were seen, notably
      late overall clinical staging and treatment adversely associated with UW-QOL
      physical functioning domains. Logistic regression was used to better understand
      the predictive factors of UW-QOL outcome and determined the final formatting of
      tables for results. These tables provide important reference data about UW-QOL
      outcome at 2 years relevant to patients at the outset of their cancer journey.
      The increasing amount of HRQOL data allows for quite detailed subgroup analysis,
      which can help give patients and the clinical team a better understanding of
      likely long-term HRQOL outcomes. How this is best utilized in clinical care needs
      further evaluation.

PMID- 25047399
TI  - Incidence of malignancies in diagnosed celiac patients: a population-based
      estimate.
AB  - OBJECTIVES: The association between celiac disease and malignancies is well
      recognized. In Finland, the prevalence of clinically diagnosed adult celiac
      disease is 0.6%. In this large, population-based cohort, we aimed at a realistic
      projection of the cancer risk. METHODS: In the period 2002-2011, the register
      comprised 32,439 adult celiac patients. This was linked with the Finnish Cancer
      Registry, which covers over 98% of diagnosed malignancies. The standardized
      incidence ratio (SIR) was calculated for the malignancies, on the basis of
      incidence figures for the whole population. A time-stratified analysis was made
      in celiac patients diagnosed after 2004 (n=11,991). Lifestyle factors, including
      smoking habits and obesity, were not obtainable. RESULTS: The overall incidence
      ratio of malignant diseases was not increased (SIR 0.94; 95% confidence intervals
      0.89-0.98), but it was >=5 years from the diagnosis of celiac disease (1.31, 1.04
      1.63). The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62-2.29), small-intestinal
      cancer (4.29; 2.83-6.24), colon cancer (1.35; 1.13-1.58), and basal cell
      carcinoma of the skin (1.13; 1.03-1.22) were increased, whereas those for lung
      cancer (0.60; 0.48-0.74), pancreatic cancer (0.73; 0.53-0.97), bladder cancer
      (0.53; 0.35-0.77), renal cancer (0.72; 0.51-0.99), and breast cancer (0.70; 0.62
      0.79) were decreased. SIR for NHL immediately after the diagnosis of celiac
      disease was 2.56 (1.37-4.38). CONCLUSIONS: There was no increased SIR of cancer
      in the whole series, but SIR was increased after 5 years from the diagnosis of
      celiac disease. The risk of breast and lung cancers was decreased. The risk of
      small-intestinal cancer and NHL was increased, but to a lesser extent than
      previously described.

PMID- 25047400
TI  - Leadership: an overview.
AB  - Despite the influence of leadership in our lives, it remains poorly understood by
      most of us. This review defines leadership as "a combination of position,
      responsibilities, attitude, skills, and behaviors that allows someone to bring
      out the best in others, and the best in their organization, in a sustainable
      manner." There are many traits and skills demonstrated by leaders. These include
      talent, drive, willpower, practical wisdom, loyalty, ethical behavior, emotional
      intelligence, integrity, self-awareness, and resilience. However, to best
      understand leadership we focus on what leaders are actually required to do,
      rather than on the skills and traits used to accomplish these tasks. We review
      nine functions that are at the core of leadership: serve as the public face of
      the organization; articulate the vision and mission; create culture; strategic
      planning; decide what to focus on; select, and develop, the right people;
      establish a decision-making process; manage your boss; and be responsible 24/7.
      All leaders operate in a specific context, during a unique point in the history
      of their organization, with a unique set of circumstances. What is required of
      the leader in one set of circumstances will change as those circumstances change.
      If the leader understands her core responsibilities, and if she develops the
      people, culture, and processes necessary to deal with a changing environment, she
      will have the self-awareness and support necessary to continue to lead
      successfully. 

PMID- 25047398
TI  - Challenges in organizing effective oncology service: inter-European variability
      in the example of head and neck cancers.
AB  - The increasing worldwide burden of cancer makes it imperative that every country
      develop a comprehensive cancer control programme. In the past, cancer control in
      Central and Eastern Europe was inadequate, particularly when compared to many
      wealthier Western European countries. We analyse interregional differences in
      Europe to the approach to comprehensive cancer care, with a focus on head and
      neck squamous cell carcinoma using the case of Poland as a representative
      example. Due to national plans major improvements have been achieved in the field
      of prevention and in radiotherapy delivery having a measurable and positive
      impact on treatment outcomes. In head and neck cancers a notable move towards
      multidisciplinary approach has been made, combining surgery, radiotherapy and
      chemotherapy accompanied by rehabilitation and social support. In Poland and
      several other Eastern and Central European countries a shortage of physicians in
      the field of oncology was noted. The main conclusion is that the special plans
      are needed in Central and Eastern Europe or those existing must be extended for
      another decade to fulfil the EU requirement of providing all European citizens
      with equal access to quality cancer care. 

PMID- 25047401
TI  - Alcohol and the risk of Barrett's esophagus: a pooled analysis from the
      International BEACON Consortium.
AB  - OBJECTIVES: Results from studies examining the association between alcohol
      consumption and the risk of Barrett's esophagus have been inconsistent. We
      assessed the risk of Barrett's esophagus associated with total and beverage
      specific alcohol consumption by pooling individual participant data from five
      case-control studies participating in the international Barrett's and Esophageal
      Adenocarcinoma Consortium. METHODS: For analysis, there were 1,282 population
      based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and
      1,169 patients with Barrett's esophagus (cases). We estimated study-specific odds
      ratios (ORs) and 95% confidence intervals (95% CI) using multivariable logistic
      regression models adjusted for age, sex, body mass index (BMI), education,
      smoking status, and GERD symptoms. Summary risk estimates were obtained by random
      effects models. We also examined potential effect modification by sex, BMI, GERD
      symptoms, and cigarette smoking. RESULTS: For comparisons with population-based
      controls, although there was a borderline statistically significant inverse
      association between any alcohol consumption and the risk of Barrett's esophagus
      (any vs. none, summary OR=0.77, 95% CI=0.60-1.00), risk did not decrease in a
      dose-response manner (Ptrend=0.72). Among alcohol types, wine was associated with
      a moderately reduced risk of Barrett's esophagus (any vs. none, OR=0.71, 95%
      CI=0.52-0.98); however, there was no consistent dose-response relationship
      (Ptrend=0.21). We found no association with alcohol consumption when cases were
      compared with GERD controls. Similar associations were observed across all strata
      of BMI, GERD symptoms, and cigarette smoking. CONCLUSIONS: Consistent with
      findings for esophageal adenocarcinoma, we found no evidence that alcohol
      consumption increases the risk of Barrett's esophagus.

PMID- 25047402
TI  - Role of Toll-like receptors 2 and 4 in mediating endothelial dysfunction and
      arterial remodeling in primary arterial antiphospholipid syndrome.
AB  - OBJECTIVE: To assess the role of Toll-like receptors (TLRs) in antiphospholipid
      antibody (aPL)-mediated vascular abnormalities in patients with primary arterial
      antiphospholipid syndrome (APS). METHODS: Forty-eight subjects participated in
      the study. Arterial function and structure and TLR pathway activation were
      determined in patients with primary arterial APS and matched controls. The
      pathogenic effects of aPL isolated from patients were assessed in wild-type (WT)
      and TLR-knockout mice. RESULTS: APS patients had endothelial dysfunction,
      arterial stiffening, and hypertrophy, as evidenced by decreased brachial artery
      endothelium-dependent flow-mediated dilation (FMD) and increased aortic pulse
      wave velocity and carotid intima-media thickness (IMT), as compared with
      controls. Plasma samples from APS patients revealed decreased nitric oxide (NO)
      availability and a pro-oxidative, proinflammatory, and prothrombotic state
      illustrated by a decrease in nitrite and an increase in lipid peroxidation, tumor
      necrosis factor alpha levels, and tissue factor (TF) levels. Furthermore, TLR
      pathway activation was found in APS patients with increased TLR-2 and TLR-4
      messenger RNA expression and increased protein levels of the activated TLR
      transduction protein interleukin-1 receptor-associated kinase 1 in peripheral
      blood mononuclear cells. Moreover, agonist-stimulated cell-surface expression of
      TLR-2 and TLR-4 in circulating monocytes was higher in APS patients than in
      controls. These changes were positively associated with IMT and negatively
      associated with FMD. Finally, aPL injection decreased mesenteric endothelium
      dependent relaxation and increased TF expression in WT mice but not in TLR-2- or
      TLR-4-knockout mice. CONCLUSION: This translational study supports the notion
      that TLR-2 and TLR-4 play a role in mediating vascular abnormalities in patients
      with primary arterial APS. TLRs thus constitute a promising pharmacologic target
      for preventing cardiovascular complications in APS.

PMID- 25047404
TI  - Adverse Outcomes Among Asian Indian Singleton Births in New Jersey, 2008-2011.
AB  - The study determined the incidence of low birth weight (LBW), small for
      gestational age (SGA), preterm birth, and perinatal morbidity among Asian Indians
      (AI) in New Jersey (NJ), as well as identified predictors of SGA. We analyzed
      birth records for singletons born to mothers identified as AI and non-Hispanic
      white from 2008 to 2011, obtained from the NJ Department of Health. For AI, rates
      of LBW and SGA were elevated, rates of preterm birth were similar, and neonatal
      intensive care unit admission was lower, compared to whites. Factors associated
      with SGA in AI included nulliparity, anemia, hypertension, placental abruption,
      and lack of prenatal care. Maternal education, marital status, substance abuse,
      and timing of prenatal care were associated with SGA in whites, but not in AI.
      SGA incidence was higher among AI despite preterm rates similar to whites. Anemia
      was associated with SGA uniquely among AI. 

PMID- 25047403
TI  - Effect of acculturation and access to care on colorectal cancer screening in low
      income Latinos.
AB  - Latinos have lower colorectal cancer screening (CRCS) and survival rates compared
      to other race/ethnic groups. This cross-sectional study examines relationships
      between acculturation, access to and utilization of healthcare services, and CRCS
      in low-income Latinos. Bilingual data collectors conducted structured interviews
      with 544 Latino men and women (>50 years) residing in the Texas-Mexico border
      area. Using a hierarchical logistic regression model, we examined the
      relationship between lifetime history of any CRCS test and indicators of
      acculturation, healthcare utilization and access to care, adjusting for socio
      demographic characteristics. Survey results revealed a 34% prevalence of CRCS.
      Participants reporting a provider recommendation for screening, regular check
      ups, higher acculturation level, and health insurance had significantly increased
      odds of CRCS. Findings indicate CRCS intervention research in Latinos should
      focus on (1) increasing physicians' recommendations for screening, (2) promoting
      regular check-ups, (3) and increasing CRC prevention efforts on less acculturated
      and uninsured groups.

PMID- 25047405
TI  - Food insecurity, depression, and social support in HIV-infected Hispanic
      individuals.
AB  - Previous research has identified an association between food insecurity and
      depression in a variety of world regions in both healthy and HIV-infected
      individuals. We examined this association in 183 HIV-infected Hispanic adults
      from the greater Boston area. We measured depression with the Burnam depression
      screen and food insecurity with the Radimer/Cornell Questionnaire. Dietary intake
      was assessed with an adapted version of the Block Food Frequency Questionnaire.
      Logistic regression models were created with depression as the outcome variable
      and food insecurity as the main predictor. In bivariate analyses, food insecurity
      was significantly associated with depression [odds ratio (OR) 2.5; 95% confidence
      interval (CI) 1.1, 5.5; p = 0.03]. When we accounted for social support, food
      insecurity was no longer significant. We found no differences in the quality or
      quantity of dietary intake between the food insecure and food secure groups. Our
      findings highlight the importance of social support in the association between
      food insecurity and depression. Food insecurity may reflect social support more
      than actual dietary intake in this population.

PMID- 25047406
TI  - [Axon-reflex based nerve fiber function assessment in the detection of autonomic
      neuropathy].
AB  - Axon-reflex-based tests of peripheral small nerve fiber function including
      techniques to quantify vasomotor and sudomotor responses following acetylcholine
      iontophoresis are used in the assessment of autonomic neuropathy. However, the
      established axon-reflex-based techniques, laser Doppler flowmetry (LDF) to assess
      vasomotor function and quantitative sudomotor axon-reflex test (QSART) to measure
      sudomotor function, are limited by technically demanding settings as well as
      interindividual variability and are therefore restricted to specialized clinical
      centers. New axon-reflex tests are characterized by quantification of axon
      responses with both temporal and spatial resolution and include "laser Doppler
      imaging (LDI) axon-reflex flare area test" to assess vasomotor function, the
      quantitative direct and indirect test of sudomotor function (QDIRT) to quantify
      sudomotor function, as well as the quantitative pilomotor axon-reflex test
      (QPART), a technique to measure pilomotor nerve fiber function using adrenergic
      cutaneous stimulation through phenylephrine iontophoresis. The effectiveness of
      new axon-reflex tests in the assessment of neuropathy is currently being
      investigated in clinical studies.

PMID- 25047407
TI  - Evaluation of the potential for a pharmacokinetic drug-drug interaction between
      armodafinil and ziprasidone in healthy adults.
AB  - BACKGROUND: Armodafinil has been studied as adjunctive therapy for major
      depressive episodes associated with bipolar I disorder. This open-label, single
      centre, 2-period study evaluated the effect of armodafinil, a moderate inducer of
      cytochrome-P450 (CYP) isoenzyme CYP3A4, on the pharmacokinetics and safety of
      ziprasidone, an atypical antipsychotic used to treat bipolar I disorder and
      metabolized in part by CYP3A4. METHODS: Thirty-five healthy subjects received
      ziprasidone (20 mg) alone and after armodafinil pretreatment (titrated to 250
      mg/day); of those, 25 were evaluable for pharmacokinetics. Pharmacokinetic
      parameters were derived from plasma concentrations of ziprasidone collected prior
      to and over the 48 h after each ziprasidone administration. Plasma concentrations
      of armodafinil and its circulating metabolites, R-modafinil acid and modafinil
      sulfone, were also obtained after repeated daily dosing of armodafinil alone.
      Safety and tolerability were assessed. RESULTS: Systemic exposure to ziprasidone
      was similar following administration alone or after pretreatment with
      armodafinil, as assessed by mean peak plasma concentration (C max, 52.1 vs 50.4
      ng/mL) and area under the plasma concentration-time curve from time 0 to infinity
      (AUC0-infinity, 544.6 vs 469.1 ng.h/mL). Geometric mean ratios of systemic
      exposure (ziprasidone alone: ziprasidone after pretreatment with armodafinil)
      were close to unity, with associated 90 % confidence intervals (CIs) within the
      range of 0.80-1.25 (C max, 0.97; 90 % CI, 0.87-1.08; AUC0-infinity, 0.86; 90 %
      CI, 0.82-0.91). Adverse events were consistent with the known safety profiles of
      each agent. CONCLUSION: Systemic exposure to ziprasidone was not affected by
      pretreatment with armodafinil. Both drugs were generally safe and well tolerated
      under the conditions studied.

PMID- 25047408
TI  - Quercetin decreases high-fat diet induced body weight gain and accumulation of
      hepatic and circulating lipids in mice.
AB  - Dietary flavonoids may protect against cardiovascular diseases (CVD). Increased
      circulating lipid levels and hepatic lipid accumulation are known risk factors
      for CVD. The aim of this study was to investigate the effects and underlying
      molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in
      mice with high-fat diet induced body weight gain and hepatic lipid accumulation.
      Adult male mice received a 40 energy% high-fat diet without or with
      supplementation of 0.33 % (w/w) quercetin for 12 weeks. Body weight gain was 29 %
      lower in quercetin fed mice (p < 0.01), while the energy intake was not
      significantly different. Quercetin supplementation lowered hepatic lipid
      accumulation to 29 % of the amount present in the control mice (p < 0.01). (1)H
      nuclear magnetic resonance serum lipid profiling revealed that the
      supplementation significantly lowered serum lipid levels. Global gene expression
      profiling of liver showed that cytochrome P450 2b (Cyp2b) genes, key target genes
      of the transcription factor constitutive androstane receptor (Car; official
      symbol Nr1i3), were downregulated. Quercetin decreased high-fat diet induced body
      weight gain, hepatic lipid accumulation and serum lipid levels. This was
      accompanied by regulation of cytochrome P450 2b genes in liver, which are
      possibly under transcriptional control of CAR. The quercetin effects are likely
      dependent on the fat content of the diet. 

PMID- 25047409
TI  - Prevalence of wheezing and atopic diseases in Austrian schoolchildren in
      conjunction with urban, rural or farm residence.
AB  - BACKGROUND: A large number of studies have consistently shown that children
      growing up on a farm have a reduced prevalence of allergic disorders. The GABRIEL
      Advanced Study was conducted in five rural areas of southern Germany,
      Switzerland, Austria and Poland to shed light on the protective 'farm effect' on
      asthma and atopic disease. Whereas, the GABRIEL Advanced Study focussed on rural
      children only, the present study incorporates data from Innsbruck town children
      also. METHODS: A screening questionnaire was developed to identify children with
      and without atopic disease within their living environment. Children were
      stratified into farm children, rural children and Innsbruck-town children. Within
      the farming environment, regular exposure to the following key factors of
      interest was predefined: the animal shed, the hay loft and farm milk. Wheezing in
      the past 12 months (W12), doctor-diagnosed (dd)-asthma, dd-allergic rhinitis and
      dd-atopic dermatitis were evaluated by using standardized questions from the
      International Study of Asthma and Allergies in Childhood (ISAAC) RESULTS: Farm
      children with regular exposure showed a lower risk for W12 (odds ratios (OR) =
      0.3; 95%; confidence interval (CI) 0.2-0.5), dd-asthma (OR = 0.4; 95% CI 0.2-0.9)
      and dd-hay fever (OR 0.2; 95% CI 0.1-0.4). The protective effect of regular
      exposure extended to rural children but included W12 and dd-hay fever only.
      Multivariate logistic regression analysis for children being regularly exposed
      revealed protective attributes for the animal shed, the hay loft and farm milk.
      CONCLUSION: These data show that regular exposure to a farming environment
      protects against wheezing, asthma and hay fever. Regarding wheezing and hay
      fever, this effect was not restricted to children living on a farm but also
      notable in rural children with regular farm contact.

PMID- 25047410
TI  - Red cell distribution width in pulmonary embolism.

PMID- 25047411
TI  - World Trade Center disaster exposure-related probable posttraumatic stress
      disorder among responders and civilians: a meta-analysis.
AB  - The World Trade Center (WTC) disaster on September 11, 2001 was an unprecedented
      traumatic event with long-lasting health consequences among the affected
      populations in the New York metropolitan area. This meta-analysis aimed to
      estimate the risk of probable posttraumatic stress disorder (PTSD) associated
      with specific types of WTC exposures. Meta-analytical findings from 10 studies of
      3,271 to 20,294 participants yielded 37 relevant associations. The pooled summary
      odds ratio (OR) was 2.05 (95% confidence interval (CI): 1.82, 2.32), with
      substantial heterogeneity linked to exposure classification, cohort type, data
      source, PTSD assessment instrument/criteria, and lapse time since 9/11. In
      general, responders (e.g. police, firefighters, rescue/recovery workers and
      volunteers) had a lower probable PTSD risk (OR = 1.61; 95% CI: 1.39, 1.87)
      compared to civilians (e.g. residents, office workers, and passersby; OR = 2.71,
      95% CI: 2.35, 3.12). The differences in ORs between responders and civilians were
      larger for physical compared to psychosocial exposure types. We also found that
      injury, lost someone, and witnessed horror were the three (out of six) most
      pernicious exposures. These findings suggest that these three exposures should be
      a particular focus in psychological evaluation and treatment programs in WTC
      intervention and future emergency preparedness efforts. 

PMID- 25047413
TI  - Bioluminescence tracking of alginate micro-encapsulated cell transplants.
AB  - Cell-based therapies to treat loss-of-function hormonal disorders such as
      diabetes and Parkinson's disease are routinely coupled with encapsulation
      strategies, but an understanding of when and why grafts fail in vivo is lacking.
      Consequently, investigators cannot clearly define the key factors that influence
      graft success. Although bioluminescence is a popular method to track the survival
      of free cells transplanted in preclinical models, little is known of the ability
      to use bioluminescence for real-time tracking of microencapsulated cells.
      Furthermore, the impact that dynamic imaging distances may have, due to freely
      floating microcapsules in vivo, on cell survival monitoring is unknown. This work
      addresses these questions by applying bioluminescence to a pancreatic substitute
      based on microencapsulated cells. Recombinant insulin-secreting cells were
      transduced with a luciferase lentivirus and microencapsulated in Ba2+ crosslinked
      alginate for in vitro and in vivo studies. In vitro quantitative bioluminescence
      monitoring was possible and viable microencapsulated cells were followed in real
      time under both normoxic and anoxic conditions. Although in vivo dispersion of
      freely-floating microcapsules in the peritoneal cavity limited the analysis to a
      qualitative bioluminescence evaluation, signals consistently four orders of
      magnitude above background were clear indicators of temporal cell survival.
      Strong agreement between in vivo and in vitro cell proliferation over time was
      discovered by making direct bioluminescence comparisons between explanted
      microcapsules and parallel in vitro cultures. Broader application of this
      bioluminescence approach to retrievable transplants, in supplement to currently
      used end-point physiological tests, could improve understanding and accelerate
      development of cell-based therapies for critical clinical applications. Copyright
      (c) 2014 John Wiley & Sons, Ltd.

PMID- 25047414
TI  - Outcomes of Percutaneous Management of Anastomotic Ureteral Strictures in Renal
      Transplantation: Chronic Nephroureteral Stent Placement with and without Balloon
      Dilatation.
AB  - PURPOSE: This study was designed o evaluate outcomes of percutaneous management
      of anastomotic ureteral strictures in renal transplants using nephroureteral
      stents with or without balloon dilatation. METHODS: A retrospective audit of
      1,029 consecutive renal transplants was performed. Anastomotic ureteral
      strictures were divided into two groups: nephroureteral stent only (NUS) and
      NUS+PTA (nephroureteral stent plus percutaneous transluminal angioplasty), with
      each cohort subdivided into early versus late presentation (obstructive uropathy
      occurring <90 day or >90 days from transplant, respectively). Overall and 6-month
      technical success were defined as removal of NUS any time with <30 % residual
      stenosis (any time lapse less or more than 6 months) and at >6 months,
      respectively. Patency was evaluated from NUS removal to last follow-up for both
      groups and compared. RESULTS: Sixty-seven transplant patients with 70 ureteric
      anastomotic strictures (6.8 %, n = 70/1,029) underwent 72 percutaneous
      treatments. 34 % were late (>90 days, n = 24/70), and 66 % were early (<90 days,
      n = 46/70). Overall technical success was 82 % (n = 59/72) and 6-month success
      was 58 % (n = 42/72). Major and minor complications were 2.8 % (n = 2/72), and
      12.5 % (n = 9/72). NUS+PTA did not improve graft survival (p = 0.354) or patency
      (p = 0.9) compared with NUS alone. There was no difference in graft survival
      between treated and nontreated groups (p = 0.74). CONCLUSIONS: There is no
      advantage to PTA in addition to placement of NUS, although PTA did not negatively
      impact graft survival or long-term patency and both interventions were safe and
      effective. Neither the late or early groups benefited from PTA in addition to
      NUS. Earlier obstructions showed greater improvement in serum creatinine than
      later obstructions.

PMID- 25047415
TI  - A multiplex nested PCR for the detection and identification of Candida species in
      blood samples of critically ill paediatric patients.
AB  - BACKGROUND: Nosocomial candidaemia is associated with high mortality rates in
      critically ill paediatric patients; thus, the early detection and identification
      of the infectious agent is crucial for successful medical intervention. The PCR
      based techniques have significantly increased the detection of Candida species in
      bloodstream infections. In this study, a multiplex nested PCR approach was
      developed for candidaemia detection in neonatal and paediatric intensive care
      patients. METHODS: DNA samples from the blood of 54 neonates and children
      hospitalised in intensive care units with suspected candidaemia were evaluated by
      multiplex nested PCR with specific primers designed to identify seven Candida
      species, and the results were compared with those obtained from blood cultures.
      RESULTS: The multiplex nested PCR had a detection limit of four Candida
      genomes/mL of blood for all Candida species. Blood cultures were positive in
      14.8% of patients, whereas the multiplex nested PCR was positive in 24.0% of
      patients, including all culture-positive patients. The results obtained with the
      molecular technique were available within 24 hours, and the assay was able to
      identify Candida species with 100% of concordance with blood cultures.
      Additionally, the multiplex nested PCR detected dual candidaemia in three
      patients. CONCLUSIONS: Our proposed PCR method may represent an effective tool
      for the detection and identification of Candida species in the context of
      candidaemia diagnosis in children, showing highly sensitive detection and the
      ability to identify the major species involved in this infection.

PMID- 25047416
TI  - Homeostasis in the mononuclear phagocyte system.
AB  - The mononuclear phagocyte system (MPS) is a family of functionally related cells
      including bone marrow precursors, blood monocytes, and tissue macrophages. We
      review the evidence that macrophages and dendritic cells (DCs) are separate
      lineages and functional entities, and examine whether the traditional view that
      monocytes are the immediate precursors of tissue macrophages needs to be refined
      based upon evidence that macrophages can extensively self-renew and can be seeded
      from yolk sac/foetal liver progenitors with little input from monocytes
      thereafter. We review the role of the growth factor colony-stimulating factor
      (CSF)1, and present a model consistent with the concept of the MPS in which local
      proliferation and monocyte recruitment are connected to ensure macrophages occupy
      their well-defined niche in most tissues. 

PMID- 25047417
TI  - Post-translational modification networks regulating FOXP3 function.
AB  - Forkhead box (FOX)P3 is a requisite transcription factor for the development and
      maintenance of immunosuppressive function of regulatory T (Treg) cells, and
      therefore for immune homeostasis. Post-translational modifications (PTMs) can
      transiently alter the functionality of transcription factors, and recent evidence
      reveals that FOXP3 can be regulated by various PTMs including acetylation,
      ubiquitination, and phosphorylation. Here, we review the current understanding of
      how these modifications control FOXP3, including regulation of DNA binding,
      transactivation potential, and proteasomal degradation. We place these findings
      in the context of the biology of Treg cells, and discuss both limitations in
      translating biochemical findings into in vivo functions and the opportunities
      presented by a better understanding of the molecular mechanisms that can
      transiently control FOXP3 activity in response to environmental cues. 

PMID- 25047418
TI  - Lymph node metastases in patients with urothelial carcinoma variants: influence
      of the specific variant on nodal histology.
AB  - OBJECTIVES: The effect that the presence of urothelial variant (UV) histologies
      has on the behavior of urothelial carcinoma remains poorly defined. The goal of
      this study is to examine the relationship between different histologic variants
      and the presence and histology of lymph node metastases. MATERIALS AND METHODS:
      Our institutional bladder cancer database was examined for all patients
      demonstrating UV at cystectomy performed between 2001 and 2012. Patients with
      primary bladder sarcoma, primary bladder adenocarcinoma, and squamous cell
      carcinoma were excluded. The cystectomy and nodal pathology reports were reviewed
      in node-positive cases with the goal of determining the relative percentages of
      UVs in the bladder and lymph nodes. RESULTS: Overall, 292 patients demonstrated
      UV at cystectomy. After excluding patients with primary adenocarcinoma, sarcoma,
      and squamous variants, 141 patients remained, of which 65 demonstrated node
      positive disease. Of these node-positive patients, 57 had slides available for
      review. Node positivity was most common in the micropapillary (MP), clear cell
      urothelial carcinoma (CC), and plasmacytoid (PC) variants. Remaining variants
      demonstrated node-positive rates ranging from 11.1% to 37.5%. When nodes were
      positive, the variants found in the nodal metastases most commonly were MP, CC,
      glandular, nested, and lymphoepitheliomalike. Median lymph node density was
      highest in PC (33%) and CC (35%) variants, although these differences were not
      statistically significant. Variant histology predominated the nodal metastases
      regardless of predominance in bladder for the MP (84%) and CC (100%) variants.
      The PC variant exhibited the high incidence of positive surgical margins.
      CONCLUSION: Lymph node metastases were most common in the MP, CC, and PC
      variants. Variant histology was present and predominated nodal histology in most
      MP and CC cases. These results suggest that the variant histology itself may be
      driving lymphatic spread in MP and CC cases. Conversely, the PC variant may be a
      marker for locally advanced and aggressive disease rather than specifically
      influencing lymphatic spread.

PMID- 25047419
TI  - Fibromyalgia and chronic fatigue syndrome caused by non-celiac gluten
      sensitivity.

PMID- 25047420
TI  - Polyostotic fibrous displasia: a case report.

PMID- 25047421
TI  - Difference in adult food group intake by sex and age groups comparing Brazil and
      United States nationwide surveys.
AB  - BACKGROUND: International comparisons of dietary intake are an important source
      of information to better understand food habits and their relationship to
      nutrition related diseases. The objective of this study is to compare food intake
      of Brazilian adults with American adults identifying possible dietary factors
      associated with the increase in obesity in Brazil. METHODS: This research used
      cross-national analyses between the United States and Brazil, including 5,420
      adults in the 2007-2008 What We Eat In America, National Health and Nutrition
      Examination Survey and 26,390 adults in the 2008-2009 Brazilian Household Budget
      Survey, Individual Food Intake. Dietary data were collected through 24 h recalls
      in the U.S. and through food records in Brazil. Foods and beverages were combined
      into 25 food categories. Food intake means and percentage of energy contribution
      by food categories to the population's total energy intake were compared between
      the countries. RESULTS: Higher frequencies of intake were reported in the United
      States compared to Brazil for the majority of food categories except for meat,
      rice and rice dishes; beans and legumes; spreads; and coffee and tea. In either
      country, young adults (20-39 yrs) had greater reports of meat, poultry and fish
      mixed dishes; pizza and pasta; and soft drinks compared to older adults (60 +
      yrs). Meat, poultry and fish mixed dishes (13%), breads (11%), sweets and
      confections (8%), pizza and pasta (7%), and dairy products (6%) were the top five
      food category sources of energy intake among American adults. The top five food
      categories in Brazil were rice and rice dishes (13%), meat (11%), beans and
      legumes (10%), breads (10%), and coffee and tea (6%). Thus, traditional plant
      based foods such as rice and beans were important contributors in the Brazilian
      diet. CONCLUSION: Although young adults had higher reports of high-calorie and
      nutrient-poor foods than older adults in both countries, Brazilian young adults
      did not consume a diet similar to Americans, indicating that it is still possible
      to reverse the current trends of incorporating Western dietary habits in Brazil.

PMID- 25047422
TI  - Design, synthesis, and potent antiepileptic activity with latent nerve
      rehabilitation of novel gamma-aminobutyric acid derivatives.
AB  - We aimed to design and synthesize novel gamma-aminobutyric acid (GABA)
      derivatives with the combination of aspirin (ASA) of nerve rehabilitative
      pharmacophores so as to develop multifunctional drugs useful in the treatment of
      neurological disorders. Twenty-four novel esters and amides of 1a were
      synthesized, biologically evaluated for antiepileptic activity with the model of
      4-aminopyridine (4-AP), and tested for their capacity of penetrating the blood
      brain barrier (BBB) with HPLC. The distribution of 8a, ASA freed by 8a, 7c, and
      ASA freed by 7c within 24 h in brain tissue was measured. The structure-activity
      relationship (SAR) was established and the data of Computer Aided Drug Design
      (CADD) showed good results. With ED50 values of 0.3684-0.5199 mmol/kg, LD50
      1.1487-1.3944 mmol/kg, and therapeutic index (TI) 2.65-3.15, compounds 8a, 3b,
      4b, 6c, and 7c exhibited better antiepileptic activities in multiples of 0.3 to
      2.2 against the control sodium valproate (VPA). Most importantly, 8a and 7c
      exhibited excellent antiepileptic activities with TI values of 3.15 and 3.12,
      respectively.

PMID- 25047423
TI  - Isolation, identification and structure elucidation of two novel process-related
      impurities of retigabine.
AB  - Retigabine was the first neuronal potassium channel opener for the treatment of
      epilepsy. During the manufacture of retigabine, two unknown impurities were
      present in laboratory batches in the range of 0.05-0.1% based upon HPLC analysis.
      These unknown impurities were obtained from the enriched reaction mother liquor
      by column chromatography. The structure of these process-related impurities were
      elucidated using FT-IR, (1)H NMR, (13)C NMR, 2D NMR (HSQC, HMBC, NOESY) and MS
      spectral data. Based on the complete spectral analysis and knowledge of the
      synthetic route of retigabine, these two new impurities were designated as ethyl
      4-fluorobenzyl(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)carbamate (impurity-II)
      and diethyl 5-((ethoxycarbonyl)(4-fluorobenzyl)amino)-2-oxo-1H-benzo[d]imidazole
      1,3(2H)-dicarboxylate (impurity-III). Impurity identification, structure
      elucidation and the formation of impurities were also discussed. 

PMID- 25047424
TI  - Modelling of vitamin A binding to tRNA.
AB  - The binding sites of retinol and retinoic acid with tRNA are located in aqueous
      solution at physiological conditions using constant tRNA concentration and
      various retinoid contents. FTIR, CD, fluorescence spectroscopic methods and
      molecular modelling were used to determine retinoid binding sites, the binding
      constant and the effects of retinol and retinoic acid complexation on tRNA
      conformation and aggregation. Structural analysis showed that retinol and
      retinoic acid bind tRNA via G-C and A-U base pairs with overall binding constants
      of Kret-tRNA=2.0 (+/-0.40)*10(4)M(-1) and Kretac-tRNA=6.0 (+/-1)*10(4)M(-1). The
      number of binding sites occupied by retinoids on tRNA were 1.4 for retinol-tRNA
      and 1.7 for retinoic acid-tRNA complexes. Hydrophobic interactions were also
      observed at high retinol and retinoic acid contents. Molecular modelling showed
      the participation of several nucleobases in retinoid-tRNA complexation with free
      binding energy of -4.36 for retinol-tRNA and -4.53kcal/mol for retinoic acid-tRNA
      adducts. 

PMID- 25047425
TI  - Detection bias may be the main cause of increased cancer incidence among
      diabetics: results from the Rotterdam Study.
AB  - AIM: Type 2 diabetes is associated with an increased cancer risk. Most studies on
      this topic analyse diabetes as a risk factor without adjusting for diabetes
      duration before cancer occurrence. This study aimed to investigate the
      association between diabetes duration and cancer risk in more detail. METHODS: In
      this prospective cohort study, diabetes diagnosis was based on clinical
      information and use of glucose lowering medication. Details on incident cancers
      were obtained via general practitioners and linkage to pathology registers. Cox
      proportional hazards models were used with onset and duration of diabetes as time
      varying determinants. RESULTS: The study comprised 10,181 individuals. Diabetes
      was associated with an increased overall risk of incident cancers (hazard ratio
      (HR) 1.2, 95% confidence interval (CI) 1.07-1.39) and pancreatic cancer (HR 2.9,
      95% CI 1.75-4.89). A diagnosis of diabetes less than three months before the
      diagnosis of cancer was associated with strongly increased risks of all- (HR 3.3,
      95% CI 2.50-4.32) and pancreatic cancers (HR 28.7, 95% CI 6.32-130.58).
      CONCLUSION: The magnitude of the association between diabetes and an increased
      risk of cancer seems to be inflated by detection- or protopathic bias. Future
      studies investigating this association should adjust for diabetes duration and
      include a plausible aetiological risk window.

PMID- 25047426
TI  - Hesperidin induces apoptosis and triggers autophagic markers through inhibition
      of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin
      and glycogen synthase kinase-3 beta signalling cascades in experimental colon
      carcinogenesis.
AB  - Abnormalities in the homeostasis mechanisms involved in cell survival and
      apoptosis are contributing factors for colon carcinogenesis. Interventions of
      these mechanisms by pharmacologically safer agents gain predominance in colon
      cancer prevention. We previously reported the chemopreventive efficacy of
      hesperidin against colon carcinogenesis. In the present study, we aimed at
      investigating the potential of hesperidin over the abrogated Aurora-A coupled pro
      survival phosphoinositide-3-kinase (PI3K)/Akt signalling cascades. Further, the
      role of hesperidin over apoptosis and mammalian target of rapamycin (mTOR)
      mediated autophagic responses were studied. Azoxymethane (AOM) induced mouse
      model of colon carcinogenesis was involved in this study. Hesperidin treatment
      was provided either in initiation/post-initiation mode respectively. Hesperidin
      significantly altered AOM mediated anti-apoptotic scenario by modulating Bax/Bcl
      2 ratio together with enhanced cytochrome-c release and caspase-3, 9 activations.
      In addition, hesperidin enhanced p53-p21 axis with concomitant decrease in cell
      cycle regulator. Hesperidin treatment caused significant up-regulation of tumour
      suppressor phosphatase and tensin homologue (PTEN) with a reduction in the
      expression of AOM mediated p-PI3K and p-Akt. Additionally, hesperidin
      administration exhibited inhibition against p-mTOR expression which in turn led
      to stimulation of autophagic markers Beclin-1 and LC3-II. Aurora-A an upstream
      regulator of PI3K/Akt pathway was significantly inhibited by hesperidin.
      Furthermore, hesperidin administration restored glycogen synthase kinase-3 beta
      (GSK-3beta) activity which in turn prevented the accumulation of oncoproteins
      beta-catenin, c-jun and c-myc. Taken together, hesperidin supplementation
      initiated apoptosis via targeted inhibition of constitutively activated Aurora-A
      mediated PI3K/Akt/GSK-3beta and mTOR pathways coupled with autophagic stimulation
      against AOM induced colon carcinogenesis. 

PMID- 25047427
TI  - Contraceptive behavior among women after abortion in Nepal.
AB  - OBJECTIVE: To investigate the timing of contraceptive use and estimate the
      discontinuation rates of temporary methods among women after abortion, or a live
      birth or stillbirth. METHODS: A sample of married women with detailed pregnancy
      and contraceptive histories was analyzed in a population-based cross-sectional
      study based on calendar data extracted from the 2011 Nepal Demographic and Health
      Survey. Kaplan-Meier cumulative and discrete-time hazard models were used to
      estimate the timing of contraceptive use and discontinuation rates among users of
      temporary methods. RESULTS: The final analysis sample included 3190 women. Of 684
      women who had had an abortion, 298 (43.6%) had not initiated any contraceptive
      use in the 12 months afterwards. Women initiated contraceptive use significantly
      earlier after abortion (hazard ratio [HR] 2.25; 95% CI, 1.96-2.59; P<0.001). The
      rate of discontinuation among contraceptive users was significantly higher in the
      postabortion group (HR 1.32; 95% CI, 1.05-1.65; P<0.05). Women who were educated,
      wealthier, had used contraceptives before the index pregnancy, had two sons and
      had autonomy initiated contraceptive use significantly earlier in the post
      abortion period than their counterparts. CONCLUSION: Postabortion contraceptive
      use is low in Nepal. Postabortion family-planning counseling and related services
      should be strengthened with systematic monitoring and follow-up interventions.

PMID- 25047428
TI  - Fluid resuscitation in sepsis: a systematic review and network meta-analysis.
AB  - BACKGROUND: Fluid resuscitation is the cornerstone of sepsis treatment. However,
      whether balanced or unbalanced crystalloids or natural or synthetic colloids
      confer a survival advantage is unclear. PURPOSE: To examine the effect of
      different resuscitative fluids on mortality in patients with sepsis. DATA
      SOURCES: MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and
      Complementary Medicine Database, and the Cochrane Central Register of Controlled
      Trials through March 2014. STUDY SELECTION: Randomized trials that evaluated
      different resuscitative fluids in adult patients with sepsis or septic shock and
      death. No language restrictions were applied. DATA EXTRACTION: Two reviewers
      extracted data on study characteristics, methods, and outcomes. Risk of bias for
      individual studies and quality of evidence were assessed. DATA SYNTHESIS: 14
      studies (18916 patients) were included with 15 direct comparisons. Network meta
      analysis at the 4-node level showed higher mortality with starches than with
      crystalloids (high confidence) and lower mortality with albumin than with
      crystalloids (moderate confidence) or starches (moderate confidence). Network
      meta-analysis at the 6-node level showed lower mortality with albumin than with
      saline (moderate confidence) and low-molecular-weight starch (low confidence) and
      with balanced crystalloids than with saline (low confidence) and low- and high
      molecular-weight starches (moderate confidence). LIMITATIONS: These trials were
      heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk
      of bias. Imprecise estimates for several comparisons in this network meta
      analysis contribute to low confidence in most estimates of effect. CONCLUSION:
      Among patients with sepsis, resuscitation with balanced crystalloids or albumin
      compared with other fluids seems to be associated with reduced mortality. PRIMARY
      FUNDING SOURCE: The Hamilton Chapter of the Canadian Intensive Care Foundation
      and the Critical Care Medicine Residency Program and Critical Care Division
      Alternate Funding Plan at McMaster University.

PMID- 25047429
TI  - Improving the treatment of port wine stain birthmarks.

PMID- 25047430
TI  - What is the optimal PDT protocol for treating port wine stains (PWS)?

PMID- 25047431
TI  - Evolving role of PDT in PWS.

PMID- 25047432
TI  - The current role of photodynamic therapy in oesophageal dysplasia and cancer.
AB  - Over the last 15 years photodynamic therapy (PDT) has become a viable treatment
      for pre-malignant and malignant disease of the oesophagus. Its initial use was in
      the palliation of oesophageal malignant obstruction bringing improved swallowing
      hence increasing nutritional intake and improving general quality of life. As the
      therapeutic boundaries of PDT have stretched, current studies look at the role of
      PDT in the treatment of pre-malignant dysplastic Barrett's epithelium and early
      malignancy as a curative mucosal ablative technique. As a curative treatment in
      early oesophageal cancer, PDT provides an alternative treatment to oesophagectomy
      for those more elderly or less medically fit patients. This paper reviews the
      uses of photodynamic therapy in oesophageal cancer with reference to the
      available publications on its use in the palliation of oesophageal cancer and
      treatment of early cancer and high grade dysplasia in Barrett's mucosa. 

PMID- 25047433
TI  - A comparison of susceptibility to photodynamic treatment between endothelial and
      tumor cells in vitro and in vivo.
AB  - BACKGROUND: Photodynamic therapy (PDT) is being widely used for treatment of
      cancer and non-malignant diseases. The mechanisms of phototoxicity to solid tumor
      are not yet completely understood. Knowledge of the inherent sensitivity of
      endothelial cells in comparison to tumor cells would be helpful to predict tumor
      response to PDT, and thereby optimize treatment protocols. METHODS AND RESULTS:
      The intrinsic sensitivity of rodent endothelial and tumor cells to PDT was
      studied using an in vitro clonogenicity assay that strictly controlled for light
      and photosensitizer exposure, as well as cellular photosensitizer and oxygen
      concentration. Taking into consideration cell size, ploidy and glutathione
      content, no significant difference in sensitivity to phototoxicity was observed
      between tumor and endothelial cells. Electron microscopy studies were also
      conducted to examine endothelial and tumor cells for differential cellular damage
      following interstitial PDT of rat prostate tumor. No evidence for selective
      damage to endothelial cells was demonstrated. CONCLUSIONS: Rodent tumor cells and
      endothelial cells are equally susceptible to Photofrin-mediated PDT damage.
      Sufficient photosensitizer accumulated in solid tumor seems to be one of the key
      factors for PDT effectiveness.

PMID- 25047434
TI  - In vivo quantification of fluorescent molecular markers in real-time: A review to
      evaluate the performance of five existing methods.
AB  - With the advent of molecular-targeted fluorescent markers, there is a renewed
      interest in fluorescence quantification methods that are based on continuous wave
      excitation and multi-spectral image acquisition. However, little is known about
      their in vivo quantification performance. We reviewed the performance of five
      selected methods by analytically describing these and varying input parameters of
      irradiance, excitation geometry, collection efficiency, autofluorescence, melanin
      content, blood volume, blood oxygenation and tissue scattering using optical
      properties representing those for human skin. We identified one method that
      corrects for variations in all parameters. This requires image acquisition before
      and after marker administration, under identical geometry. Hence, it is suited
      for applications where the site of interest can be relocated (e.g. anaesthetized
      animals and dermatology). For applications where relocation is not possible, we
      identified a second method where the uncertainty in the fluorescence signal was
      +/-20%. Hence, use of these methods can substantially aid in vivo fluorescence
      quantification compared to use of the raw fluorescence signal, as this changed by
      more than 3 orders of magnitude. Since these methods can be computed in real
      time, they are of particular interest for applications where direct feedback is
      critical, as diagnostic screening or image-guided surgery. 

PMID- 25047435
TI  - Solitary rectal ulcer syndrome-The role of autofluorescence colonoscopy.
AB  - BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a rare disorder of the
      rectum but it causes differential diagnosis problems. AIM: To determine the
      potential use of autofluorescence colonoscopy (AFC) in diagnosis of SRUS.
      MATERIAL AND METHODS: We performed 1618 colonoscopies. After the medical history
      was taken white light colonoscopy was performed. The tissue samples were taken
      for routine pathological examination. When SRUS was histopathologically confirmed
      AFC was performed by means of OncoLIFE. The mean time lapse between the two
      colonoscopies was 4 weeks. During AFC numerical colour value (NCV) of
      autofluorescence of SRUS lesions was noted. RESULTS: During 1618 colonoscopies
      six persons were diagnosed as having solitary rectal ulcer syndrome (0.37%). The
      mean age was 43.8 years. There were two men and four women. In our material the
      endoscopic spectrum was: three (50%) polypoid lesions, two (33.33%) flat ulcers
      and one case (16.66%) of isolated, local erythema with hyperemia. We did not
      observe decrease of fluorescence in case of polipoid and flat ulcer lesions (NCV
      0.39-0.67; mean 0.525) and little decrease of fluorescence in case of erythema
      lesion (NCV -0.94). CONCLUSION: Autofluorescence colonoscopy by means of OncoLIFE
      appears to be a promising approach in diagnosis of SRUS. The estimation of
      numerical colour value which is an objective test of autofluorescence intensity,
      facilitates the differential diagnosis and helps to chose the right management of
      SRUS.

PMID- 25047436
TI  - Tetherless fiber-coupled optical sources for extended metronomic photodynamic
      therapy.
AB  - BACKGROUND: Metronomic photodynamic therapy (mPDT) involves the delivery of a low
      fluence rate of light and photosensitizing drug, continuously and over an
      extended period. However, in mPDT trials, there has been a perceived need for
      light sources that can deliver light reliably for extended periods, while being
      small enough to be tolerated by small animals. METHODS: We report on the
      development of tetherless, lightweight, fiber-coupled optical sources for in vivo
      delivery of interstitial mPDT. Two forms are reported, based on diode lasers and
      light-emitting diodes (LEDs), the latter types weighing only 16.5g. RESULTS: The
      prototypes have been well tolerated in preliminary trials on tumor-bearing rat
      models and can currently provide stable levels of performance for upwards of 5
      days. We also report an extension of the concept to units coupled to several
      optical fibers to enable simultaneous irradiation of multiple locations in
      tissue. CONCLUSION: These prototypes fulfill a current need for reliable mPDT
      optical sources for use with animal models. They also serve as the foundation for
      the development of fiber-coupled sources for use in future clinical trials.

PMID- 25047437
TI  - Visualization of basal cell carcinoma by fluorescence diagnosis and independent
      component analysis.
AB  - Photodynamic detection (PDD) of skin tumours is based on the visualization of a
      fluorophores, with the ability to accumulate in tumour tissue, by the use of
      fluorescence imaging. Of particular importance is the application of delta-5
      aminolaevulinic acid (ALA) that, through the process of biosynthesis causes
      formation of the protoporphyrin IX (PpIX). The PpIX has the ability of selective
      fluorescence after basal cell carcinoma (BCC) has been treated with ALA. Higher
      concentration of PpIX in tumour tissue compared to surrounding normal skin is the
      basis for PDD. Our contribution in this preliminary study is application of the
      independent component analysis (ICA) to extract the BCC spatial map, by
      processing fluorescent RGB image acquired under excitation with 405nm light.
      Comparative performance analysis with other two widely used image processing
      methods: ratio imaging and optimal threshold based imaging, reveals that ICA
      produces BCC spatial map that is most consistent in term of diagnostic quality by
      both visual assessment and calculation of the BCC demarcation line. We believe
      this represents a solid basis for the design of a compact and low-cost multi
      spectral fluorescence imaging system, capable for real time calculation of the
      skin tumour demarcation. 

PMID- 25047438
TI  - Comparison of aminolevulinic acid (ALA)-thermogel-PDT with methyl-ALA-thermogel
      PDT in basal cell carcinoma.
AB  - BACKGROUND: Aminolevulinic acid (ALA) and light irradiation is a treatment option
      in basal cell carcinomas (BCC). The development of ALA-esters with potential for
      greater penetration depth promises higher therapeutic success. In a pilot study,
      we hypothesized that the cytotoxic effect of methyl-ALA (mALA) photodynamic
      therapy (PDT) leads to a higher success rate compared with ALA-PDT when both are
      topically applied in a thermogel. METHODS: Twenty-four patients with 112
      superficial BCC were treated with either 10% ALA- or mALA-thermogel. After an
      accumulation time of at least 3h, the lesions were illuminated with a diode
      laser. The power density was 0.1W/cm(2) and the energy density was 120J/cm(2).
      After intervals of 12 weeks and 6 months, the therapeutic efficacy was assessed
      by clinical examination. RESULTS: Sixty percent of the tumors were treated
      successfully in the first session. All but 3% of the remaining tumors could be
      treated with a second or third course of therapy. CONCLUSION: Although mALA
      should have a greater penetration depth, the therapeutic outcome of this
      preliminary study showed no difference between treatments. The final proof of
      this preliminary result will require further study.

PMID- 25047439
TI  - Interstitial in vivo ALA-PpIX mediated metronomic photodynamic therapy (mPDT)
      using the CNS-1 astrocytoma with bioluminescence monitoring.
AB  - BACKGROUND: We report the first truly metronomic delivery of photodynamic therapy
      using the rat-derived CNS-1 astrocytoma, a model with close histopathology with
      human brain tumours. METHODS: Metronomic PDT (mPDT) was delivered to CNS-1
      bearing female Lewis rats. 5-Aminoluvelinic acid was delivered continuously
      through drinking water, while light was delivered via tetherless, light-weight,
      LED-based fiber coupled optical sources. Tumour burden before and after mPDT
      treatment was determined using bioluminescence imaging (BLI). RESULTS:
      Preliminary studies demonstrated that 24h of continuous mPDT illumination was
      capable of destroying small tumours (7 days post-implant). The reduction or
      elimination of tumour was confirmed using BLI and corroborated by histology.
      Additional studies showed that 24 and 48h continuous mPDT illumination had the
      capability to delay tumour re-growth by a period corresponding to approximately
      two doubling times. Animals given 4-day mPDT did not show any signs of tumour re
      growth via BLI at 26 days post-tumour implantation. CONCLUSIONS: In summary,
      these results demonstrate the feasibility of delivering mPDT for extended
      periods, as well as its potential as a treatment for small brain tumours.

PMID- 25047440
TI  - In vitro light distributions from intracranial PDT balloons.
AB  - BACKGROUND: Optical fibres can be placed in balloons to deliver light for
      intracranial photodynamic therapies. METHOD: A series of fibres, with either
      cleaved ends or terminating in cylindrical diffusers, housed in two different
      balloons, containing various solutions were investigated. The aim of the
      experiments performed was to assess which equipment produced the most uniform
      illumination field. A balloon manufactured by Medlight (ML) was compared to one
      adapted from a Rush Silkomed (RS) paediatric urinary catheter. Measurements were
      made at regular angular intervals, within parallel horizontal planes surrounding
      the balloons. RESULTS: The inter-planar and intra-planar variability of the
      illumination field was assessed. Experimental combinations with high intra-planar
      variability included those using a cleaved optical fibre, without a linear
      diffuser. Experimental combinations with high inter-planar variability included
      those using cleaved optical fibres, and some of the balloons inflated with
      solutions not containing optical scattering media. CONCLUSIONS: The best
      experimental combination, from those assessed in this paper, would include a
      diffuser and either the RS balloon inflated with a liquid containing some
      Intralipid, or the ML balloon which was required to be filled only with saline.

PMID- 25047441
TI  - Annual Conference of BMLA, and the First Meeting of the UK-PDPDT Interest Group,
      Manchester Museum of Science and Technology, 7-8 June, 2007.

PMID- 25047442
TI  - Heterologous expression and biochemical and functional characterization of a
      recombinant alpha-type myotoxin inhibitor from Bothrops alternatus snake.
AB  - Venomous and non-venomous snakes possess phospholipase A2 (PLA2) inhibitory
      proteins (PLIs) in their blood serum. This study shows the expression and
      biochemical and functional characterization of a recombinant alpha inhibitor from
      Bothrops alternatus snake, named rBaltMIP. Its expression was performed in Pichia
      pastoris heterologous system, resulting in an active recombinant protein. The
      expressed inhibitor was tested regarding its ability to inhibit the phospholipase
      activity of different PLA2s, showing slight inhibitions especially at the molar
      ratios of 1:1 and 1:3 (PLA2:PLI). rBaltMIP was also effective in decreasing the
      myotoxic activity of the tested toxins at molar ratios greater than 1:0.4
      (myotoxin:PLI). The inhibition of the myotoxic activity of different Asp49 (BthTX
      II and PrTX-III) and Lys49 (BthTX-I and PrTX-I) myotoxins was also performed
      without the prior incubation of myotoxins/inhibitor in order to analyze the real
      possibility of using snake plasma inhibitors or recombinant inhibitors as
      therapeutic agents for treating envenomations. As a result, rBaltMIP was able to
      significantly inhibit the myotoxicity of Lys49 myotoxins. Histopathological
      analysis of the gastrocnemius muscles of mice showed that the myotoxins are able
      to induce severe damage to the muscle fibers of experimental animals by
      recruiting a large number of leukocyte infiltrates, besides forming an intense
      accumulation of intercellular fluid, leading to local edema. When those myotoxins
      were incubated with rBaltMIP, a reduction of the damage site could be observed.
      Furthermore, the cytotoxic activity of Asp49 PLA2s and Lys49 PLA2-like enzymes on
      C2C12 cell lines was decreased, as shown by the higher cell viabilities after
      preincubation with rBaltMIP. Heterologous expression would enable large-scale
      obtainment of rBaltMIP, thus allowing further investigations for the elucidation
      of possible mechanisms of inhibition of snake PLA2s, which have not yet been
      fully clarified. 

PMID- 25047443
TI  - Triptolide, a diterpene, inhibits osteoclastogenesis, induced by RANKL signaling
      and human cancer cells.
AB  - Most bone-related diseases are characterized by excessive bone resorption by
      osteoclasts. Receptor activator of nuclear factor-kappa B (NF-kappaB) ligand
      (RANKL) has emerged as a major mediator of bone resorption, commonly associated
      with cancer and chronic inflammatory diseases. Thus inhibitors of RANKL signaling
      have a potential in preventing bone loss. In the present study, we investigated
      the ability of triptolide, a diterpenoid isolated from Thunder of God Vine, to
      inhibit signaling by receptor activator of NF-kappaB (RANK) and its ligand
      (RANKL) and to modulate osteoclastogenesis induced by RANKL and human cancer
      cells. We found that triptolide suppressed RANKL-induced differentiation of
      precursor cells to osteoclasts, and also inhibited osteoclast formation induced
      by human breast tumor cells (MDA-MB-231), multiple myeloma cells (U266) and
      prostate tumor cells (PC-3). Triptolide inhibited RANKL-induced NF-kappaB
      activation in osteoclast precursor cells by inhibiting IkappaBalpha kinase
      activation, IkappaBalpha phosphorylation, and IkappaBalpha degradation. Our
      results suggest that triptolide effectively inhibits RANKL-induced NF-kappaB
      activation and RANKL- and tumor cell-induced osteoclastogenesis. This warrants
      further study of triptolide as a potential therapy for osteoporosis and cancer
      associated bone loss. 

PMID- 25047444
TI  - Anticancer activity of CopA3 dimer peptide in human gastric cancer cells.
AB  - CopA3 is a homodimeric alpha-helical peptide derived from coprisin which is a
      defensin-like antimicrobial peptide that was identified from the dung beetle,
      Copris tripartitus. CopA3 has been reported to have anticancer activity against
      leukemia cancer cells. In the present study, we investigated the anticancer
      activity of CopA3 in human gastric cancer cells. CopA3 reduced cell viability and
      it was cytotoxic to gastric cancer cells in the MTS and LDH release assay,
      respectively. CopA3 was shown to induce necrotic cell death of the gastric cancer
      cells by flow cytometric analysis and acridine orange/ethidium bromide staining.
      CopA3-induced cell death was mediated by specific interactions with
      phosphatidylserine, a membrane component of cancer cells. Taken together, these
      data indicated that CopA3 mainly caused necrosis of gastric cancer cells,
      probably through interactions with phosphatidylserine, which suggests the
      potential utility of CopA3 as a cancer therapeutic.

PMID- 25047445
TI  - Amyloid pore-channel hypothesis: effect of ethanol on aggregation state using
      frog oocytes for an Alzheimer's disease study.
AB  - Alzheimer's disease severely compromises cognitive function. One of the
      mechanisms to explain the pathology of Alzheimer's disease has been the
      hypotheses of amyloid-pore/channel formation by complex Abeta-aggregates.
      Clinical studies suggested the moderate alcohol consumption can reduces
      probability developing neurodegenerative pathologies. A recent report explored
      the ability of ethanol to disrupt the generation of complex Abeta in vitro and
      reduce the toxicity in two cell lines. Molecular dynamics simulations were
      applied to understand how ethanol blocks the aggregation of amyloid. On the other
      hand, the in silico modeling showed ethanol effect over the dynamics assembling
      for complex Abeta-aggregates mediated by break the hydrosaline bridges between
      Asp 23 and Lys 28, was are key element for amyloid dimerization. The amyloid
      pore/channel hypothesis has been explored only in neuronal models, however
      recently experiments suggested the frog oocytes such an excellent model to
      explore the mechanism of the amyloid pore/channel hypothesis. So, the used of
      frog oocytes to explored the mechanism of amyloid aggregates is new, mainly for
      amyloid/pore hypothesis. Therefore, this experimental model is a powerful tool to
      explore the mechanism implicates in the Alzheimer's disease pathology and also
      suggests a model to prevent the Alzheimer's disease pathology.

PMID- 25047446
TI  - Suppressing subordinate reproduction provides benefits to dominants in
      cooperative societies of meerkats.
AB  - In many animal societies, a small proportion of dominant females monopolize
      reproduction by actively suppressing subordinates. Theory assumes that this is
      because subordinate reproduction depresses the fitness of dominants, yet the
      effect of subordinate reproduction on dominant behaviour and reproductive success
      has never been directly assessed. Here, we describe the consequences of
      experimentally preventing subordinate breeding in 12 groups of wild meerkats
      (Suricata suricatta) for three breeding attempts, using contraceptive injections.
      When subordinates are prevented from breeding, dominants are less aggressive
      towards subordinates and evict them less often, leading to a higher ratio of
      helpers to dependent pups, and increased provisioning of the dominant's pups by
      subordinate females. When subordinate breeding is suppressed, dominants also show
      improved foraging efficiency, gain more weight during pregnancy and produce
      heavier pups, which grow faster. These results confirm the benefits of
      suppression to dominants, and help explain the evolution of singular breeding in
      vertebrate societies. 

PMID- 25047447
TI  - A comparison of Narrative Exposure Therapy and Prolonged Exposure therapy for
      PTSD.
AB  - The purpose of this review was to compare and contrast Prolonged Exposure (PE)
      and Narrative Exposure Therapy (NET). We examined the treatment manuals to
      describe the theoretical foundation, treatment components, and procedures,
      including the type, manner, and focus of exposure techniques and recording
      methods used. We examined extant clinical trials to investigate the range of
      treatment formats reported, populations studied, and clinical outcome data. Our
      search resulted in 32 studies on PE and 15 studies on NET. Consistent with prior
      reviews of PTSD treatment, it is evident that PE has a solid evidence base and
      its current status as a first line treatment for the populations studied to this
      date is warranted. We argue that NET may have advantages in treating complex
      traumatization seen in asylum seekers and refugees, and for this population NET
      should be considered a recommended treatment. NET and PE have several
      commonalities, and it is recommended that studies of these treatments include a
      broader range of populations and trauma types to expand the current knowledge on
      the treatment of PTSD. 

PMID- 25047448
TI  - The effectiveness of Multisystemic Therapy (MST): a meta-analysis.
AB  - Multisystemic Therapy (MST) is a well-established intervention for juvenile
      delinquents and/or adolescents showing social, emotional and behavioral problems.
      A multilevel meta-analysis of k=22 studies, containing 332 effect sizes,
      consisting of N=4066 juveniles, was conducted to examine the effectiveness of
      MST. Small but significant treatment effects were found on delinquency (primary
      outcome) and psychopathology, substance use, family factors, out-of-home
      placement and peer factors, whereas no significant treatment effect was found for
      skills and cognitions. Moderator analyses showed that study characteristics
      (country where the research was conducted, efficacy versus effectiveness, and
      study quality), treatment characteristics (single versus multiple control
      treatments and duration of MST treatment), sample characteristics (target
      population, age, gender and ethnicity) and outcome characteristics (non-specific
      versus violent/non-violent offending, correction for pretreatment differences,
      and informant type) moderated the effectiveness of MST. MST seems most effective
      with juveniles under the age of 15, with severe starting conditions. Furthermore,
      the effectiveness of MST may be improved when treatment for older juveniles is
      focused more on peer relationships and risks and protective factors in the school
      domain. 

PMID- 25047449
TI  - Lateralized task shift effects in Broca's and Wernicke's regions and in visual
      word form area are selective for conceptual content and reflect trial history.
AB  - We investigated whether lateralized BOLD-fMRI activations in Broca's region,
      Wernicke's region and visual word form area (VWFA) reflect task shift costs and
      to which extent these effects are specific to language related task shifts. We
      employed a linguistic one-back memory paradigm where participants (n=58) on each
      trial responded to whether a given word was the same as the previous word. In
      concordance with previous findings we found that conceptual shifts (CS), i.e. new
      words, elicited a strongly left-lateralized response in all three regions
      compared to repeat words. Words were sometimes presented through the visual
      modality (read) and sometimes through the auditory modality (spoken). This
      enabled the study of perceptual modality shifts (PS) relative to trials that
      stayed in the same modality as the previous trials. Again, we found a strongly
      left-lateralized effect in all regions. This was independent of whether the word
      was a CS or not, suggesting that linguistic translation across modalities taxes
      the same system as CS. Response shifts (RS), on the other hand, when shifting
      from one response (e.g. reporting a repeat word) to another (e.g. reporting a new
      word) did not yield an observable left lateralized response in any of the
      regions, suggesting that the lateralized task shift cost effects in these regions
      are not shared by all types of task shifts. Lateralization for individual tasks
      was found to be correlated across brain regions, but not across tasks, suggesting
      that lateralization may not be a unitary phenomenon, but vary across participants
      according to task demands. Both response time and lateralization were found to
      reflect the demands not only of the current trial but also of the previous trial,
      illustrating the context dependency of even simple cognitive tasks. 

PMID- 25047450
TI  - Photooxidation of tryptophan leading to 2-aminoacetophenone--a possible reason
      for the untypical aging off-flavor in wine.
AB  - 2-Aminoacetophenone (AAP) was recognized as the key compound for the so-called
      untypical aging off-flavor (UTA) in Vitis vinifera wines. In this study, it was
      shown that AAP can be formed by photooxidation of free and protein-bound
      tryptophan (TRP) in combination with a subsequent storage in model wine.
      Solutions of TRP and lysozyme were exposed to artificial sunlight both in the
      presence and in the absence of the photosensitizer riboflavin. Aliquots of the
      irradiation batches were stored in model wine solutions containing tartaric acid,
      sulfite and ethanol in different combinations. AAP formation could be identified
      from both free and bound (lysozyme) TRP, while free TRP resulted in higher
      yields. The presence of riboflavin during irradiation generally favored the AAP
      formation. AAP formation increased with increasing irradiation times, but AAP was
      not detectable, if TRP was directly incubated in model wine. Not only the
      irradiation time but also the storage time of model wines favored the formation
      of AAP. Concerning the model wine composition, it became evident that the
      presence of tartaric acid resulted in the highest AAP formation during storage. 

PMID- 25047451
TI  - Methylenetetrahydrofolate reductase C677T polymorphism and type 2 diabetes
      mellitus in Chinese population: a meta-analysis of 29 case-control studies.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate
      metabolism, had significant effects on the homocysteine levels. The common
      functional MTHFR C677T polymorphism had been extensively researched. Several
      studies had evaluated the relationship between MTHFR C677T polymorphism and type
      2 diabetes mellitus (T2DM), but the results were still controversial in the
      Chinese Han population. This meta-analysis was conducted to evaluate the
      relationship between MTHFR C677T polymorphism and T2DM in the Chinese Han
      population. METHODS: We searched the relevant studies in multiple electronic
      databases, which published up to December 2013. We reviewed and extracted data
      from all the included studies on the relationship between MTHFR C677T
      polymorphism and T2DM in the Chinese Han population. The odds ratios (ORs) and
      their 95% confidence intervals (95%CIs) were used to evaluate the relationship.
      Fixed-effects and random-effects meta-analysis were used to pool ORs by the
      heterogeneity. Publication bias and sensitivity analysis were also examined.
      RESULTS: 29 studies were finally included in our meta-analysis, which contained
      4656 individuals with T2DM and 2127 healthy controls. There was a significant
      relationship between MTHFR C677T polymorphism and T2DM under dominant (OR: 1.70,
      95% CI: 1.42-2.02), recessive (OR: 1.48, 95% CI: 1.21-1.80), homozygous (OR:
      1.89, 95% CI: 1.47-2.42), heterozygous (OR: 1.58, 95% CI: 1.33-1.87), and
      additive (OR: 1.46, 95% CI: 1.28-1.68) genetic model in a random-effects model.
      Subgroup analysis also reached similar results. Sensitivity analysis indicated
      that the overall result were dependable. CONCLUSIONS: There was a significant
      relationship between MTHFR C677T polymorphism and T2DM in the Chinese Han
      population. The results of our meta-analysis suggested that MTHFR 677T allele
      might be a risk genetic factor of T2DM in the Chinese Han population.

PMID- 25047452
TI  - The effect of TIP on pneumovirus-induced pulmonary edema in mice.
AB  - BACKGROUND: Pulmonary edema plays a pivotal role in the pathophysiology of
      respiratory syncytial virus (RSV)-induced respiratory failure. In this study we
      determined whether treatment with TIP (AP301), a synthetic cyclic peptide that
      mimics the lectin-like domain of human TNF, decreases pulmonary edema in a mouse
      model of severe human RSV infection. TIP is currently undergoing clinical trials
      as a therapy for pulmonary permeability edema and has been shown to decrease
      pulmonary edema in different lung injury models. METHODS: C57BL/6 mice were
      infected with pneumonia virus of mice (PVM) and received TIP or saline (control
      group) by intratracheal instillation on day five (early administration) or day
      seven (late administration) after infection. In a separate set of experiments the
      effect of multiple dose administration of TIP versus saline was tested. Pulmonary
      edema was determined by the lung wet-to-dry (W/D) weight ratio and was assessed
      at different time-points after the administration of TIP. Secondary outcomes
      included clinical scores and lung cellular response. RESULTS: TIP did not have an
      effect on pulmonary edema in different dose regimens at different time points
      during PVM infection. In addition, TIP administration did not affect clinical
      severity scores or lung cellular response. CONCLUSION: In this murine model of
      severe RSV infection TIP did not affect pulmonary edema nor course of disease.

PMID- 25047453
TI  - Characterization of subtle brain abnormalities in a mouse model of Hedgehog
      pathway antagonist-induced cleft lip and palate.
AB  - Subtle behavioral and cognitive deficits have been documented in patient cohorts
      with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits
      are associated with structural brain abnormalities but have been limited to
      adolescent and adult populations where brain plasticity during infancy and
      childhood may be a confounding factor. Here, we employed high resolution magnetic
      resonance microscopy to examine primary brain morphology in a mouse model of
      OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway
      antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including
      unilateral and bilateral cleft lip and palate, cleft of the secondary palate
      only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to
      controls, cyclopamine-exposed fetuses exhibited volumetric differences in several
      brain regions, including hypoplasia of the pituitary gland and olfactory bulbs,
      hyperplasia of the forebrain septal region, and expansion of the third ventricle.
      However, in affected fetuses the corpus callosum was intact and normal division
      of the forebrain was observed. This argues that temporally-specific Hh signaling
      perturbation can result in typical appearing OFCs in the absence of
      holoprosencephaly--a condition classically associated with Hh pathway inhibition
      and frequently co-occurring with OFCs. Supporting the premise that some forms of
      OFCs co-occur with subtle brain malformations, these results provide a possible
      ontological basis for traits identified in clinical populations. They also argue
      in favor of future investigations into genetic and/or environmental modulation of
      the Hh pathway in the etiopathogenesis of orofacial clefting.

PMID- 25047454
TI  - Comparison of our self-designed rotary self-locking intramedullary nail and
      interlocking intramedullary nail in the treatment of long bone fractures.
AB  - OBJECTIVE: The purpose of this study is to compare the clinical effects of our
      self-designed rotary self-locking intramedullary nail (RSIN) and interlocking
      intramedullary nail (IIN) for long bone fractures. METHODS: A retrospective study
      was performed in 1,704 patients who suffered bone fractures and underwent RSIN or
      IIN operation in our hospital between March 1999 and March 2013, including 494
      with femoral fractures, 572 with humeral fractures, and 638 with tibial
      fractures. Among them, 634 patients were followed up for more than 1 year. The
      operative time, intraoperative blood loss, postoperative complications, healing
      rate, and the excellent and good rate of functional recovery were compared
      between two groups. RESULTS: Compared with IIN group, RSIN group exhibited
      significantly shorter operative time and less intraoperative blood loss no matter
      for humeral, femoral, or tibial fractures (all p < 0.001). The healing rate in
      patients with more than 1 year follow-up was significantly higher in RSIN group
      for femoral and tibial fractures (both p < 0.05). In RSIN group, no nail breakage
      or loosening occurred, but radial nerve injury and incision infection were
      respectively observed in one patient with humeral fracture. In IIN group, nail
      breakage or loosening occurred in 7 patients with femoral fractures and 16
      patients with tibial fractures, radial nerve injury was observed in 8 patients
      with humeral fractures, and incision infection was present in 2 patients with
      humeral fractures and 1 patient with femoral fracture. The complication rate of
      IIN group was significantly higher than that of RSIN group (p < 0.05). However,
      there were no significant differences in the excellent and good rate of shoulder,
      elbow, knee, and ankle joint functional recovery between RSIN group and IIN
      group. CONCLUSION: RSIN may be a reliable and practical alternative method for
      the treatment of long bone fractures.

PMID- 25047455
TI  - Extending Miles & Snow's strategy choice typology to the German hospital sector.
AB  - Hospitals' strategy choices represent highly relevant factors that affect
      organizational performance and survival. This study assesses the differences
      among hospitals' strategic choices. This strategy definition and assessment
      reflects the typology proposed by Miles and Snow, who distinguish four strategy
      types: defender, analyzer, prospector, and reactor. Synthesis of empirical
      evidence from previous studies that have applied Miles and Snow's typology in the
      hospital sector using various methodological approaches and measures provides
      hints for industry-specific patterns and avenues for further research. Taking an
      extended view of strategic choice, the authors conduct an empirical survey of a
      sample of 178 German hospitals. The authors apply a multi-item measure of the
      Miles and Snow strategy types in the hospital sector and identify hybrid strategy
      types that deviate from the four strategy types defined by Miles and Snow.
      Overall, seven distinct strategy types emerge from this analysis. There exist
      three distinct hybrid types in particular. Strategy choice is systematically
      related to hospital size and teaching status but not to ownership and location.
      The significant variance in performance for the seven different strategy types
      justifies the distinction between them. The results support the idea of industry
      specific strategy choices. Policy makers should analyze the structural context in
      which hospitals operate and intervene through political and regulatory means. 

PMID- 25047456
TI  - Tai Chi for improvement of motor function, balance and gait in Parkinson's
      disease: a systematic review and meta-analysis.
AB  - BACKGROUND: Recently, several studies assessed the effectiveness of Tai Chi for
      Parkinson's disease (PD), but the role of Tai Chi in the management of PD
      remained controversial. Therefore, the purpose of this systematic review is to
      evaluate the evidence on the efficacy of Tai Chi for PD. METHODS: Six English and
      Chinese electronic databases, up to April 2014, were searched to identify
      relevant studies. The risk of bias in eligible studies was assessed by Cochrane
      Collaboration's tools. The primary outcomes were motor function, balance and gait
      in individuals with PD. Standardized mean difference (SMD) and 95% confidence
      intervals (CI) of random-effect model were calculated. And heterogeneity was
      assessed based on the I2 statistic. RESULTS: 7 randomized controlled trials and 1
      non-randomized controlled trial were eligible. The aggregated results suggested
      that Tai Chi showed beneficial effects in improving motor function (SMD, -0.57;
      95% CI -1.11 to -0.04; p = 0.03), balance (SMD, 1.22; 95% CI 0.80 to 1.65;
      p<0.00001) and functional mobility (SMD, 1.06; 95% CI 0.68 to 1.44; p<0.00001) in
      patients with PD, but not in improving gait velocity (SMD, -0.02; 95% CI -0.58 to
      0.54; p = 0.94), step length (SMD, -0.00; 95% CI -0.57 to 0.56; p = 0.99), or
      gait endurance (SMD, 0.53; 95% CI -0.07 to 1.12; p = 0.08). Comparing with other
      active therapies, however, Tai Chi only showed better effects in improving
      balance (SMD, 0.74; 95% CI 0.38 to 1.10; p<0.0001). CONCLUSION: Tai Chi should be
      a valid complementary and alternative therapy for PD, especially in improving
      motor function and balance. However, more studies with long follow-up are warrant
      to confirm the current finding of Tai Chi for PD.

PMID- 25047457
TI  - A prospective, randomized comparison of posterior stabilized versus cruciate
      substituting total knee arthroplasty: a preliminary report with minimum 2-year
      results.
AB  - We compared 56 patients who received a PS post/cam tibial insert and 55 patients
      who received a more congruent anterior-lipped tibial insert. We hypothesized that
      clinical outcomes would be equivalent and that tourniquet time and intraoperative
      blood loss would differ. The mean follow-up is 45 months (30-57 months). Clinical
      and radiographic outcomes were equivalent for both groups, except that male PS
      patients received significantly more transfusions than male CS patients (P<.039)
      and tourniquet time was significantly longer for all patients in the PS group
      (P<.015). At the minimum 2-year follow-up in this ongoing study, the results
      demonstrate equivalent functional and radiographic outcomes of the 2 devices, and
      significant differences in the perioperative findings of transfusion rates and
      tourniquet times.

PMID- 25047458
TI  - Safety and efficacy of edoxaban, an oral factor xa inhibitor, for
      thromboprophylaxis after total hip arthroplasty in Japan and Taiwan.
AB  - Edoxaban, an oral direct factor Xa inhibitor, has proven antithrombotic efficacy.
      In a multicenter, phase II study, 264 total hip arthroplasty (THA) patients
      randomly received edoxaban 15 or 30 mg once daily or enoxaparin 2000IU (20-mg)
      twice daily for 11-14 days. Thromboembolic event incidences were 3.8% (3/78),
      2.8% (2/72), and 4.1% (3/74) for edoxaban 15-mg, 30-mg, and enoxaparin,
      respectively (P=1.00). Edoxaban-induced prolongation of prothrombin time,
      international normalized ratio, and activated partial thromboplastin time were
      proportional to plasma edoxaban concentration. Major or clinically relevant non
      major bleeding incidences were 2.2% (2/89), 1.2% (1/85), and 2.3% (2/87) for
      edoxaban 15-mg, 30-mg, and enoxaparin, respectively (P=1.00). Once-daily edoxaban
      showed similar efficacy and safety to enoxaparin for prevention of thromboembolic
      events in patients undergoing THA.

PMID- 25047459
TI  - Synthesis of a dimeric magnesium(I) compound by an Mg(I)/Mg(II) redox reaction.
AB  - The synthesis of dimeric magnesium(I) compounds of the general type RMgMgR
      (R=monoanionic substituent) is still a challenging synthetic task and limited to
      few examples with sterically demanding ligands with delocalized CN-frameworks
      that all have been accessed by Na or K metal reduction of magnesium(II) halide
      precursors. Here we report on the synthesis of a novel diiminophosphinato
      magnesium(I) compound that has been synthesized by a facile redox reaction using
      a known magnesium(I) complex. The synthetic strategy may be applicable to other
      ligand systems and can help expand the class of low oxidation state magnesium
      complexes even if reductions with Na or K are unsuccessful. The new dimeric
      magnesium(I) complex has been structurally characterized and undergoes a C-C
      coupling reaction with tert-butylisocyanate.

PMID- 25047461
TI  - Investigations on the pattern of linkage disequilibrium and selection signatures
      in the genomes of German Pietrain pigs.
AB  - The aim of this study was to study the population structure, to characterize the
      LD structure and to define core regions based on low recombination rates among
      SNP pairs in the genome of Pietrain pigs using data from the PorcineSNP60
      BeadChip. This breed is a European sire line and was strongly selected for lean
      meat content during the last decades. The data were used to map signatures of
      selection using the REHH test. In the first step, selection signatures were
      searched genome-wide using only core haplotypes having a frequency above 0.25. In
      the second step, the results from the selection signature analysis were matched
      with the results from the recently conducted genome-wide association study for
      economical relevant traits to investigate putative overlaps of chromosomal
      regions. A small subdivision of the population with regard to the geographical
      origin of the individuals was observed. The extent of LD was determined genome
      wide using r(2) values for SNP pairs with a distance <=5 Mb and was on average
      0.34. This comparable low r(2) value indicates a high genetic diversity in the
      Pietrain population. Six REHH values having a p-value < 0.001 were genome-wide
      detected. These were located on SSC1, 2, 6 and 17. Three positional candidate
      genes with potential biological roles were suggested, called LOC100626459,
      LOC100626014 and MIR1. The results imply that for genome-wide analysis especially
      in this population, a higher marker density and higher sample sizes are required.
      For a number of nine SNPs, which were successfully annotated to core regions, the
      REHH test was applied. However, no selection signatures were found for those
      regions (p-value < 0.1). 

PMID- 25047460
TI  - An evaluation of enteral nutrition practices and nutritional provision in
      children during the entire length of stay in critical care.
AB  - BACKGROUND: Provision of optimal nutrition in children in critical care is often
      challenging. This study evaluated exclusive enteral nutrition (EN) provision
      practices and explored predictors of energy intake and delay of EN advancement in
      critically ill children. METHODS: Data on intake and EN practices were collected
      on a daily basis and compared against predefined targets and dietary reference
      values in a paediatric intensive care unit. Factors associated with intake and
      advancement of EN were explored. RESULTS: Data were collected from 130 patients
      and 887 nutritional support days (NSDs). Delay to initiate EN was longer in
      patients from both the General Surgical and congenital heart defect (CHD)
      Surgical groups [Median (IQR); CHD Surgical group: 20.3 (16.4) vs General
      Surgical group: 11.4 (53.5) vs Medical group: 6.5 (10.9) hours; p <= 0.001].
      Daily fasting time per patient was significantly longer in patients from the
      General Surgical and CHD Surgical groups than those from the Medical group [% of
      24 h, Median (IQR); CHD Surgical group: 24.0 (29.2) vs General Surgical group:
      41.7 (66.7) vs Medical group: 9.4 (21.9); p <= 0.001]. A lower proportion of
      fluids was delivered as EN per patient (45% vs 73%) or per NSD (56% vs 73%) in
      those from the CHD Surgical group compared with those with medical conditions.
      Protein and energy requirements were achieved in 38% and 33% of the NSDs. In a
      substantial proportion of NSDs, minimum micronutrient recommendations were not
      met particularly in those patients from the CHD Surgical group. A higher delivery
      of fluid requirements (p < 0.05) and a greater proportion of these delivered as
      EN (p < 0.001) were associated with median energy intake during stay and delay of
      EN advancement. Fasting (31%), fluid restriction (39%) for clinical reasons,
      procedures requiring feed cessation and establishing EN (22%) were the most
      common reasons why target energy requirements were not met. CONCLUSIONS:
      Provision of optimal EN support remains challenging and varies during
      hospitalisation and among patients. Delivery of EN should be prioritized over
      other "non-nutritional" fluids whenever this is possible.

PMID- 25047462
TI  - Challenges in the local treatment of large abdominal embryonal rhabdomyosarcoma.
AB  - BACKGROUND: Embryonal rhabdomyosarcoma is the most common pediatric soft tissue
      sarcoma. The best local treatment in large, nonmetastatic primary unresected
      nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however
      unclear. METHODS: We analyzed patients with LARME treated in four consecutive CWS
      trials. All diagnoses were confirmed by reference reviews. Treatment included
      multiagent chemotherapy and local treatment of the primary tumor with surgery
      and/or radiotherapy. The impact of primary debulking surgery (PDS) also was
      studied. RESULTS: One hundred patients <21 years with a median age of 4 years had
      LARME. Sixty-one of them had a tumor >10 cm in diameter at diagnosis. PDS was
      performed in 19 of 100 children. The outcomes of patients with PDS were similar
      to those of the other patients. In 36 children, the tumor was resected after
      induction chemotherapy; 60 RME were irradiated. The toxic effects of
      radiochemotherapy were not significantly increased compared with the
      nonirradiated patients. With a median follow-up of 10 years, the 5-year EFS and
      OS were 52 +/- 10 and 65 +/- 9 %, respectively. Significant risk factors in
      multivariate analysis were age >10 years; no achievement of complete remission;
      and inadequate secondary local treatment, defined as incomplete secondary
      resection or no radiation. CONCLUSIONS: Children with LARME have a fair
      prognosis, despite an often huge tumor size and unfavorable primary site, if the
      tumors can either be resected or irradiated following induction chemotherapy. PDS
      was only performed in a small subgroup. Radiation performed concomitantly with
      chemotherapy did not increase the acute toxicity significantly.

PMID- 25047463
TI  - Arsenic trioxide inhibits CXCR4-mediated metastasis by interfering miR
      520h/PP2A/NF-kappaB signaling in cervical cancer.
AB  - BACKGROUND: Arsenic apparently affects numerous intracellular signal transduction
      pathways and causes many alterations leading to apoptosis and differentiation in
      malignant cells. We and others have demonstrated that arsenic inhibits the
      metastatic capacity of cancer cells. Here we present additional mechanistic
      studies to elucidate the potential of arsenic as a promising therapeutic
      inhibitor of metastasis. METHODS: The effects of arsenic trioxide (ATO) on human
      cervical cancer cell lines migration and invasion were observed by transwell
      assays. In experimental metastasis assays, cancer cells were injected into tail
      veins of severe combined immunodeficient mice for modeling metastasis. The
      mechanisms involved in ATO regulation of CXCR4 were analyzed by immunoblot, real
      time polymerase chain reaction, and luciferase reporter assays.
      Immunohistochemistry was utilized to identify PP2A/C and CXCR4 protein
      expressions in human cervical cancer tissues. RESULTS: ATO inhibited CXCR4
      mediated cervical cancer cell invasion in vitro and distant metastasis in vivo.
      We determined that ATO modulates the pivotal nuclear factor-kappa B (NF
      kappaB)/CXCR4 signaling pathway that contributes to cancer metastasis.
      Substantiating our findings, we demonstrated that ATO activates PP2A/C activity
      by downregulating miR-520h, which results in IKK inactivation, IkappaB
      dephosphorylation, NF-kappaB inactivation, and, subsequently, a reduction in
      CXCR4 expression. Furthermore, PP2A/C was reduced during cervical carcinogenesis,
      and the loss of PP2A/C expression was closely associated with the nodal status of
      cervical cancer patients. CONCLUSIONS: Our results indicate a functional link
      between ATO-mediated PP2A/C regulation, CXCR4 expression, and tumor-suppressing
      ability. This information will be critical in realizing the potential for synergy
      between ATO and other anti-cancer agents, thus providing enhanced benefit in
      cancer therapy.

PMID- 25047464
TI  - Utility of the proximal margin frozen section for resection of gastric
      adenocarcinoma: a 7-Institution Study of the US Gastric Cancer Collaborative.
AB  - BACKGROUND: The proximal gastric margin dictates the extent of resection for
      gastric adenocarcinoma (GAC). The value of achieving negative margins via
      additional gastric resection after a positive proximal margin frozen section (FS)
      is unknown. METHODS: The US Gastric Cancer Collaborative includes all patients
      who underwent resection of GAC at seven institutions from 2000-2012.
      Intraoperative proximal margin FS data and final permanent section (PS) data were
      classified as R0 or R1, respectively; positive distal margins were excluded. The
      primary aim was to evaluate the impact on local recurrence of converting a
      positive proximal FS-R1 margin to a PS-R0 final margin by additional resection.
      Secondary endpoints were recurrence-free survival (RFS) and overall survival
      (OS). RESULTS: Of 860 patients, 520 had a proximal margin FS and 67 were
      positive. Of these, 48 were converted to R0 on PS by additional resection. R0
      proximal margin was achieved in 447 patients (86 %), PS-R1 in 25 (5 %), and
      converted FS-R1-to-PS-R0 in 48 (9 %). The median follow-up was 44 months. Local
      recurrence was significantly decreased in the converted FS-R1-to-PS-R0 group
      compared to the PS-R1 group (10 vs. 32 %; p = 0.01). Median RFS was similar
      between the FS-R1-to-PS-R0 and PS-R1 cohorts (25 vs. 20 months; p = 0.49),
      compared to 37 months for the PS-R0 group. Median OS was similar between the FS
      R1-to-PS-R0 conversion and PS-R1 groups (36 vs. 26 months; p = 0.14) compared to
      50 months for the PS-R0 group. On multivariate analysis, increasing T-stage and N
      stage were associated with worse OS; the FS-R1-to-PS-R0 proximal margin
      conversion was not significantly associated with improved RFS (p = 0.68) or OS (p
      = 0.44). CONCLUSION: Conversion of a positive intraoperative proximal margin
      frozen section during gastric cancer resection may decrease local recurrence, but
      it is not associated with improved RFS or OS. This may guide decisions regarding
      the extent of resection.

PMID- 25047468
TI  - Factors influencing the length of stay after radical cystectomy: implications for
      cancer care and perioperative management.
AB  - INTRODUCTION: Although radical cystectomy (RC) is the gold standard treatment for
      muscle invasive bladder cancer it is associated with perioperative complications,
      readmissions, and a prolonged length of hospital stay (PLOS). We explored the
      perioperative factors associated with a PLOS after RC and subsequent long-term
      outcomes. MATERIAL AND METHODS: Consecutive patients with urothelial bladder
      cancer undergoing RC with curative intent at our institution were classified into
      two groups: LOS <12 days and PLOS >=12 days. Clinicopathological variables were
      compared on univariate and multivariable analysis. Complications, re-admissions,
      adjuvant chemotherapy use, recurrence free survival (RFS), and overall survival
      (OS) were compared between the two groups. Competing risk analysis was performed
      for bladder cancer specific mortality (BCSM). RESULTS: 330 patients were included
      in the analysis (median LOS = 9 days [IQR = 8-11]) of which, 274 patients (83 %)
      had a LOS <12 days (median = 8 days [IQR = 7-10]) and 56 patients (17 %) had a
      PLOS >=12 days (median = 16 days [IQR = 13-21.5]). Only female gender, older age,
      and perioperative complications were associated with a PLOS. 90 day readmission
      rates were similar (p = 0.75). No difference was seen for BCSM, RFS, or adjuvant
      chemotherapy usage between the two groups. However, OS was significantly worse
      for PLOS (median OS = 27.7 vs. 45.6 months [p = 0.046]; HR = 1.53 [95 % CI = 1.01
      2.33]). CONCLUSION: Both female and elderly patients should receive preoperative
      counseling about their increased risk of a PLOS after RC. Patients who experience
      a PLOS are at greater risk for subsequent all-cause mortality. These patient
      groups may benefit from proactive interventions.

PMID- 25047467
TI  - Readmission after pancreatic resection: causes and causality pattern.
AB  - BACKGROUND: Readmission rates have been targeted for cost/reimbursement control.
      Our goal was to identify causes for readmission and delineate the pattern of
      early and late readmission. METHODS: Between 2011 and 2012, a total of 490
      patients underwent pancreaticoduodenectomy, distal pancreatectomy or central
      pancreatectomy. Logistic regression was used to identify predictors of
      readmission. K-medoids clustering was performed to identify the major readmission
      subgroups. RESULTS: Median postoperative length of stay (LOS) was 7 days, and the
      30- and 90-day readmission rates were 23 and 29 %, respectively. The most common
      cause for 30-day readmissions was procedure-related infections (58 %), while the
      most common cause for 31-90-day readmissions was failure to thrive and
      chemotherapy-related symptoms (38 %). Independent predictors of 30-day
      readmissions were central pancreatectomy, discharge with a drain, pancreatic duct
      <3 mm, previous abdominal surgery, and postoperative LOS. Independent predictors
      for 31-90-day readmissions were age and preoperative serum carcinoembryonic
      antigen. Cancer-related covariates were more common in the 31-90-day readmission
      group. Postoperative carbohydrate antigen 19-9 levels were twofold higher in the
      31-90-day readmission group compared with the no readmission group (p = 0.03). K
      medoids clustering identified a subgroup where 74 % of readmissions occur at a
      median of 7 days after discharge. CONCLUSIONS: Readmissions after pancreatic
      operations are procedure-related in the first 30 days, but those after this
      period are influenced by the natural history of the underlying diagnosis. The
      readmission penalty policy should account for the timing of readmission and the
      natural history of the underlying disease and procedure. Early follow-up for
      patients at high risk for readmission may minimize early readmissions.

PMID- 25047469
TI  - The hMLH1 -93G>A promoter polymorphism is associates with outcomes in oral
      squamous cell carcinoma patients.
AB  - BACKGROUND: The aim of this study was to investigate the impact of hMLH1
      polymorphisms on treatment outcomes in patients with oral squamous cell carcinoma
      (OSCC). METHODS: Genotypings were performed by direct DNA sequencing in
      peripheral blood leukocytes from 185 male OSCC patients. Patients received
      primary surgery with or without adjuvant radiotherapy. Two hMLH1 tag single
      nucleotide polymorphisms (SNPs)-rs1800734 (-93G>A in the promoter) and rs1540354
      (in the third intron)-were chosen from the HapMap project. Overall survival (OS)
      and disease-free survival (DFS) were compared between different genotypes.
      RESULTS: The hMLH1 rs1800734 and rs1540354 polymorphisms were in weak linkage
      disequilibrium (r (2) = 0.456). OSCC patients with the rs1800734 AA genotype had
      a significantly poor prognosis in both OS and DFS. This SNP can also predict the
      outcomes of OSCC patients with postoperative adjuvant radiotherapy, especially in
      advanced stage; however, no significant differences in patient outcomes were
      found for the hMLH1 rs1540354 genotypes. CONCLUSIONS: Our results demonstrate
      that the hMLH1 -93G>A SNP is found to be associated with patient outcomes in
      OSCC. This SNP can also predict their treatment outcome of radiotherapy.

PMID- 25047470
TI  - Incremental risk associated with contralateral prophylactic mastectomy and the
      effect on adjuvant therapy.
AB  - BACKGROUND: Contralateral prophylactic mastectomy (CPM) is expected to add
      surgical morbidity but this incremental risk has not yet been defined. We sought
      to quantify the additional risks associated with CPM and determine how these
      risks influence the time to adjuvant therapy. METHODS: We identified women
      undergoing mastectomy for unilateral breast cancer and stratified them according
      to the use of CPM and the presence and laterality of surgical complications. We
      measured time to adjuvant therapy. RESULTS: Of 352 patients, 205 (58 %) underwent
      unilateral mastectomy (UM) and 147 (42 %) underwent bilateral mastectomy (BM) [BM
      = UM + CPM]. Overall, 94/352 (27 %) women suffered 112 complications (BM: 46/147
      [31 %] vs. UM: 48/205 [23 %]; p = 0.11), of which hematoma, skin necrosis,
      cellulitis, or seroma accounted for 94/112 (84 %) complications. Reoperation was
      required in 37/352 (10 %) women. Among those undergoing BM, morbidity occurred
      only in the prophylactic breast in 19/147 (13 %) women and risk did not differ
      with immediate reconstruction (13/108 [12 %]) or without (6/39 [15 %]). Of these
      19 patients, 10 (53 %) required reoperation. Women with any complication had a
      longer interval to adjuvant therapy when compared with those without (49 days vs.
      40 days; p < 0.001). When stratified according to side, complications in the
      prophylactic breast were not associated with a delay in treatment (UM: 58 days
      vs. BM: prophylactic side; 41 days vs. BM: cancer side: 50 days; p = 0.73).
      CONCLUSIONS: CPM confers additional morbidity in one in eight women, of whom half
      require reoperation. Despite this, in our series CPM did not delay adjuvant
      therapy. Given the rising incidence of patients seeking CPM, they should be
      informed of this risk.

PMID- 25047472
TI  - Reasons for re-excision after lumpectomy for breast cancer: insight from the
      American Society of Breast Surgeons Mastery(SM) database.
AB  - BACKGROUND: There is marked variability of re-excision rates after initial
      lumpectomy for breast cancer. Reasons for re-excision and variability across
      surgeons have not been well documented. We hypothesized the American Society of
      Breast Surgeons (ASBrS) Mastery(SM) Program can identify reasons for re-excision.
      METHODS: Data from January 1 to 7 November 2013 were evaluated in the ASBrS
      Mastery(SM) Program to determine re-excision lumpectomy rate (RELR). On 1 June
      2013, a tool to track reasons for re-excision was developed. Variation in re
      excision rate by surgeon and patient characteristics was performed by Chi square
      test and Fisher's test for univariate analysis, then logistic regression with
      backwards elimination method for multivariate analysis. RESULTS: For 6,725
      patients undergoing initial lumpectomy for cancer, 328 surgeons reported 1,451
      (21.6 %) patients had one or more re-excisions. The most common reasons for re
      excision were ink positive margins in 783 (49.7 %), margin <1 mm (34.3 %), and
      margin 1-2 mm (7.2 %). By multivariate analysis, re-excision rates were lower in
      patients aged less than 35 years, with White (non-) Hispanic ethnicity, and,
      among surgeons in solo practice, more years in practice and higher-volume
      practice. CONCLUSION: Half of re-excisions after initial lumpectomy were
      performed for margins that are positive. Most of the remainder were for negative
      close (<1-2 mm) margins. This information corroborates surgeon survey data
      regarding reasons for re-excision and provides proof of concept the Mastery(SM)
      Program can capture surgical outcome data in real time, providing opportunity and
      a method for future performance improvement.

PMID- 25047471
TI  - Comparison of nodal metastasis between BRCA mutation carriers and non-BRCA
      mutation carriers with breast cancer.
AB  - OBJECTIVE: This study evaluates whether nodal status differs between breast
      cancer patients with BRCA mutations and those confirmed not to harbor mutations.
      METHODS: A prospective database identified patients with breast cancer who
      underwent genetic testing and axillary staging. Comparative variables included
      age, as well as tumor characteristics such as size, grade, lymphovascular
      invasion (LVI), estrogen receptor, progesterone receptor, human epidermal growth
      factor receptor 2 (HER2-neu), and nodal status. RESULTS: Overall, 235 patients
      with breast cancer underwent genetic testing for BRCA mutations from June 2000 to
      May 2012. Of these patients, 74 (31.4 %) were found to express BRCA 1 and/or 2
      mutations, and 161 (68.5 %) patients were verified to have no detectable BRCA
      mutation. Among the entire 235 patients tested, 92 (39.1 %) were found to have
      nodal disease. In univariable analysis, only LVI and tumor size correlated with
      presence of nodal metastasis. Of the 74 BRCA mutation carriers, 34 (45.9 %) had
      nodal metastasis compared with 58 of the 161 (36 %; p = 0.15) patients without a
      BRCA mutation. BRCA mutation carriers with nodal disease were more likely to have
      poorly differentiated tumors than those without mutations who had nodal disease
      (24/33 [72.7 %] vs. 27/57 [47.4 %]; p = 0.027). CONCLUSION: BRCA mutations are
      not themselves predictive of nodal metastasis. Patients with BRCA mutations did
      not have a statistically significant higher prevalence of nodal metastasis than
      those without mutations.

PMID- 25047473
TI  - American Society of Breast Surgeons presidential address: breast cancer surgery
      is dead...or is it?

PMID- 25047474
TI  - Implementing a screening tool for identifying patients at risk for hereditary
      breast and ovarian cancer: a statewide initiative.
AB  - BACKGROUND: The Georgia Breast Cancer Genomic Health Consortium is a partnership
      created with funding from the Centers for Disease Control and Prevention (CDC) to
      the Georgia Department of Public Health to reduce cancer disparities among high
      risk minority women. The project addresses young women at increased risk for
      hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts.
      METHODS: The consortium provides education and collects surveillance data using
      the breast cancer genetics referral screening tool (B-RST) available at
      www.BreastCancerGeneScreen.org . The HBOC educational protocol was presented to
      73 staff in 6 public health centers. Staff used the tool during the collection of
      medical history. Further family history assessments and testing for mutations in
      the BRCA1/2 genes were facilitated if appropriate. RESULTS: Data was collected
      from November 2012 through December 2013, including 2,159 screened women. The
      majority of patients identified as black/African American and were 18-49 years
      old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110
      patients who agreed to be contacted provided a detailed family history. A total
      of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when
      family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1
      patient was positive for a BRCA2 mutation, and 1 patient was found to carry a
      variant of uncertain significance. CONCLUSIONS: The introduction of genomics
      practice within public health departments has provided access to comprehensive
      cancer care for uninsured individuals. The successful implementation of the B-RST
      into public health centers demonstrates the opportunity for integration of HBOC
      screening into primary care practices.

PMID- 25047475
TI  - Initial experience with genomic profiling of heavily pretreated breast cancers.
AB  - BACKGROUND: Rapidly evolving advances in the understanding of theorized unique
      driver mutations within individual patient's cancers, as well as dramatic
      reduction in the cost of genomic profiling, have stimulated major interest in the
      role of such testing in routine clinical practice. The aim of this study was to
      report our initial experience with genomic testing in heavily pretreated breast
      cancer patients. METHODS: Patients with primary or recurrent breast cancer
      managed at any of our five hospitals and whose malignancy had failed to respond
      to therapy or had progressed on all recognized standard-of-care options were
      offered the opportunity to have their cancer undergo next-generation sequencing
      genomic profiling. RESULTS: Of a total of 101 patients, 98 (97 %) had at least
      one specific genomic alteration identified. A total of 465 different somatic
      genetic abnormalities were revealed in this group of patients. Although 52 % of
      patients were found to have an abnormality for which an U.S. Food and Drug
      Administration (FDA)-approved drug was available, 69 % of patients had an FDA
      approved agent for an indication other than breast cancer. The most common
      genomic alterations of potential clinical consequence were PIK3 (25 %), FGFR1 (16
      %), AKT (11 %), PTEN (10 %), ERBB2 (8 %), JAK2 (6 %), and RAF1 (5 %).
      CONCLUSIONS: Almost all advanced breast cancers possess at least one well
      characterized genomic alteration that might be actionable at the clinical level.
      Further, in most cases, a plausible argument can be advanced for the potential
      biological and clinical relevance of an FDA-approved antineoplastic agent not
      currently indicated in the treatment of breast cancer.

PMID- 25047476
TI  - Pilot study to evaluate feasibility of image-guided breast-conserving therapy in
      the advanced multimodal image-guided operating (AMIGO) suite.
AB  - BACKGROUND: The rate of reexcision in breast-conserving surgery remains high,
      leading to delay in initiation of adjuvant therapy, increased cost, increased
      complications, and negative psychological impact to the patient.1 (-) 3 We
      initiated a phase 1 clinical trial to determine the feasibility of the use of
      intraoperative magnetic resonance imaging (MRI) to assess margins in the advanced
      multimodal image-guided operating (AMIGO) suite. METHODS: All patients received
      contrast-enhanced three-dimensional MRI while under general anesthesia in the
      supine position, followed by standard BCT with or without wire guidance and
      sentinel node biopsy. Additional margin reexcision was performed of suspicious
      margins and correlated to final pathology (Fig. 1). Feasibility was assessed via
      two components: demonstration of safety and sterility and acceptable duration of
      the operation and imaging; and adequacy of intraoperative MRI imaging for
      interpretation and its comparison to final pathology. Fig. 1 Schema of AMIGO
      trial RESULTS: Eight patients (mean age 48.5 years), 4 with stage I breast cancer
      and 4 with stage II breast cancer, were recruited. All patients underwent
      successful BCT in the AMIGO suite with no AMIGO-specific complications or break
      in sterility during surgery. The mean operative time was 113 min (range 93-146
      min). CONCLUSIONS: Our experience with AMIGO suggests that it is feasible to use
      intraoperative MRI imaging to evaluate margin assessment in real time. Further
      research is required to identify modalities that will lead to a reduction in
      reexcision in breast cancer therapy.

PMID- 25047477
TI  - Treatment of clinical T2N0M0 esophageal cancer.
AB  - BACKGROUND: Management of clinical T2N0M0 (cT2N0M0) esophageal cancer remains
      controversial. We reviewed our institutional experience over 21 years (1990-2011)
      to determine clinical staging accuracy, optimal treatment approaches, and factors
      predictive of survival in this patient population. METHODS: Patients with cT2N0M0
      esophageal cancer determined by endoscopic ultrasound (EUS) were identified
      through a prospectively collected database. Demographics, perioperative data, and
      outcomes were examined. Cox regression model and Kaplan-Meier plots were used for
      statistical survival analysis. RESULTS: A total of 731 patients underwent
      esophagectomy, of whom 68 cT2N0M0 patients (9 %) were identified. Fifty-seven
      patients (84 %) had adenocarcinoma. Thirty-three patients (48.5 %) were treated
      with neoadjuvant chemoradiation followed by surgery, and 35 underwent surgical
      resection alone. All resections except one included a transthoracic approach with
      two-field lymph node dissection. Thirty-day operative mortality was 2.9 %. Only 3
      patients (8.5 %) who underwent surgery alone had T2N0M0 disease identified by
      pathology: the disease of 15 (42.8 %) was found to be overstaged and 17 (48.5 %)
      understaged after surgery. Understaging was more common in poorly differentiated
      tumors (p = 0.03). Nine patients (27.2 %) had complete pathologic response after
      chemoradiotherapy. Absence of lymph node metastases (pN0) was significantly more
      frequent in the neoadjuvant group (29 of 33 vs. 21 of 35, p = 0.01). Median
      follow-up was 44.2 months. Overall 5-year survival was 50.8 %. On multivariate
      analysis, adenocarcinoma (p = 0.001) and pN0 after resection (p = 0.01) were
      significant predictors of survival. CONCLUSIONS: EUS was inaccurate in staging
      cT2N0M0 esophageal cancer in this study. Poorly differentiated tumors were more
      frequently understaged. Adenocarcinoma and absence of lymph node metastases (pN0)
      were independently predictive of long-term survival. pN0 status was significantly
      more common in patients undergoing neoadjuvant therapy, but long-term survival
      was not affected by neoadjuvant therapy. A strategy of neoadjuvant therapy
      followed by resection may be optimal in this group, especially in patients with
      disease likely to be understaged.

PMID- 25047478
TI  - Survival analysis of contralateral prophylactic mastectomy: a question of
      selection bias.
AB  - BACKGROUND: Rates of contralateral prophylactic mastectomy (CPM) in women with
      breast cancer have increased, but most studies fail to show a survival benefit.
      We evaluated survival among CPM patients compared to patients undergoing single
      mastectomy (SM). METHODS: The Surveillance, Epidemiology, and End Results
      database was used to identify unilateral breast cancer patients who underwent
      mastectomy with/without CPM from 1998 to 2010. Case-control analysis was
      performed with CPM cases matched to SM controls on the basis of age group,
      race/ethnicity, extent of surgery, grade, T classification, N classification,
      estrogen receptor status, and propensity score. Survival analyses included Kaplan
      Meier curves and univariate and multivariate proportional hazard models to
      determine factors associated with disease-specific (DSS) and overall survival
      (OS). RESULTS: A total of 26,526 CPM patients were identified. On multivariate
      regression analysis, increasing age, greater extent of surgery, increasing T and
      N stage, African American race, Hispanic ethnicity, poorly differentiated grade,
      and estrogen receptor negativity were associated with increased risk of death.
      CPM was associated with improved DSS (HR 0.86, 95 % CI 0.79-0.93) and even
      greater OS (HR 0.76, 95 % CI 0.71-0.81) compared with SM. Contralateral breast
      cancer (CBC) occurred in 1.6 % of women in the cohort. Removing CBC cases from
      analysis had little impact on CPM DSS (HR 0.86, 95 % CI 0.79-0.93) and OS (0.77,
      95 % CI 0.72-0.82) suggesting that prevention of CBC by CPM does not explain the
      observed survival benefit. CONCLUSIONS: CPM rates continue to rise. The improved
      DSS and OS observed with CPM support selection bias. Prospective trials are
      needed to determine cohorts of patients most likely to benefit from CPM.

PMID- 25047479
TI  - Clinicopathologic characteristics of incidentally identified pheochromocytoma.
AB  - BACKGROUND: Pheochromocytomas are rare neuroendocrine tumors. With the widespread
      use of cross-sectional imaging, increasing numbers are identified incidentally,
      but their clinicopathologic traits have been incompletely characterized. METHODS:
      We performed a retrospective cohort study of patients who underwent initial
      adrenalectomy for pheochromocytoma (1997-2014). Patients were classified as
      identified by guided investigation (GIP) if imaging was performed for symptoms or
      surveillance and as incidentally identified pheochromocytomas (IIP) if imaging
      was performed for other indications. Student's t test, Chi square test, or rank
      sum tests were used as appropriate. RESULTS: Of 126 patients, 47 % were IIP (n =
      59). IIP patients had more nonspecific symptoms, including abdominal or back pain
      (39.0 vs. 6.0 %, p < 0.001), but lower rates of classic symptoms, such as
      hypertension (54.2 vs. 77.6 %, p = 0.005), palpitations or arrhythmias (18.9 vs.
      50.0 %, p = 0.001), flushing or diaphoresis (25.4 vs. 46.3 %, p = 0.015), and
      headache (20.3 vs. 44.8 %, p = 0.004). IIP was associated with lower median 24
      hour urine metanephrine (2102 vs. 7299 MUg, p = 0.020), normetanephrine (2253 vs.
      4383 MUg, p = 0.005), and epinephrine (23 vs. 116 MUg, p = 0.004) levels.
      Histopathology demonstrated no difference between IIP and GIP in malignant
      traits, including extraadrenal extension (8.6 vs. 12.3 %, p = 0.568), capsular
      invasion (26.9 vs. 20.3 %, p = 0.133), lymphovascular invasion (25.0 vs. 24.6 %,
      p = 0.264), and necrosis (32.4 vs. 20.0 %, p = 0.224). Rates of malignancy were
      equivalent (5.1 vs. 6.0 %, p = 0.862) between IIP and GIP cohorts. CONCLUSIONS:
      Half of patients presenting for surgical resection of pheochromocytoma were
      identified incidentally. These patients had equivalent rates of malignancy and
      pathologic traits associated with malignant potential and require definitive
      evaluation and early surgical referral.

PMID- 25047480
TI  - Less remains better: morbidity after axillary surgery.

PMID- 25047481
TI  - Contralateral prophylactic mastectomy and survival: an ongoing challenge.

PMID- 25047482
TI  - Discovery and validation of gene-linked diagnostic SNP markers for assessing
      hybridization between Largemouth bass (Micropterus salmoides) and Florida bass
      (M. floridanus).
AB  - Efforts to improve recreational fisheries have included widespread stocking of
      Micropterus floridanus outside its native range of peninsular Florida.
      Hybridization of Florida bass (M. floridanus) with largemouth bass (Micropterus
      salmoides) has now dramatically expanded beyond a naturally occurring intergrade
      zone in the southeast U.S. In recent years, there has been growing interest in
      protecting the genetic integrity of native basses and assessing the impact and
      nature of M. salmoides/M. floridanus introgression from the standpoint of
      hatchery and sport-fishery managers, fish biologists, ecologists and evolutionary
      biologists. Here, we conducted RNA-seq-based sequencing of the transcriptomes of
      M. salmoides, M. floridanus and their F1 hybrid and identified a set of 3674 SNP
      markers with fixed-allelic differences from 2112 unique genes. We then developed
      a subset of 25 of these markers into a single diagnostic multiplex assay and
      validated its capacity for assessing integrity and hybridization in hatchery and
      wild populations of largemouth and Florida bass. The availability of this
      resource, high-quality transcriptomes and a large set of gene-linked SNPs, should
      greatly facilitate functional and population genomics studies in these key
      species and allow the identification of traits and processes under selection
      during introgressive hybridization.

PMID- 25047485
TI  - Court-authorised caesarean section.

PMID- 25047483
TI  - Late Eocene to early Oligocene quantitative paleotemperature record: evidence
      from continental halite fluid inclusions.
AB  - Climate changes within Cenozoic extreme climate events such as the Paleocene
      Eocene Thermal Maximum and the First Oligocene Glacial provide good opportunities
      to estimate the global climate trends in our present and future life. However,
      quantitative paleotemperatures data for Cenozoic climatic reconstruction are
      still lacking, hindering a better understanding of the past and future climate
      conditions. In this contribution, quantitative paleotemperatures were determined
      by fluid inclusion homogenization temperature (Th) data from continental halite
      of the first member of the Shahejie Formation (SF1; probably late Eocene to early
      Oligocene) in Bohai Bay Basin, North China. The primary textures of the SF1
      halite typified by cumulate and chevron halite suggest halite deposited in a
      shallow saline water and halite Th can serve as an temperature proxy. In total,
      one-hundred-twenty-one Th data from primary and single-phase aqueous fluid
      inclusions with different depths were acquired by the cooling nucleation method.
      The results show that all Th range from 17.7 degrees C to 50.7 degrees C,with the
      maximum homogenization temperatures (ThMAX) of 50.5 degrees C at the depth of
      3028.04 m and 50.7 degrees C at 3188.61 m, respectively. Both the ThMAX presented
      here are significantly higher than the highest temperature recorded in this
      region since 1954 and agree with global temperature models for the year 2100
      predicted by the Intergovernmental Panel on Climate Change.

PMID- 25047486
TI  - McDonald transvaginal cervical cerclage since 1957: from its roots in Australia
      into worldwide contemporary practice.

PMID- 25047487
TI  - Authors' reply: Cerclage or cervical occlusion--what's the difference?

PMID- 25047488
TI  - Cerclage or cervical occlusion--what's the difference?

PMID- 25047489
TI  - Authors' reply: How well can pelvic floor muscles with major defects contract? A
      cross-sectional comparative study six weeks post partum using transperineal 3D/4D
      ultrasound and manometer.

PMID- 25047490
TI  - How well can pelvic floor muscles with major defects contract? A cross-sectional
      comparative study six weeks post partum using transperineal 3D/4D ultrasound and
      manometer.

PMID- 25047491
TI  - A comparison of the long-term consequences of vaginal delivery versus caesarean
      section of the prevalence, severity and bothersomeness of urinary incontinence
      subtypes: a national cohort study in primiparous women.

PMID- 25047492
TI  - Authors' reply: A comparison of the long-term consequences of vaginal delivery
      versus caesarean section of the prevalence, severity and bothersomeness of
      urinary incontinence subtypes: a national cohort study in primiparous women.

PMID- 25047493
TI  - A report from #BlueJC: 'How to manage incontinence after childbirth?'.

PMID- 25047494
TI  - Authors' comment: A report from #BlueJC: 'How to manage incontinence after
      childbirth?'.

PMID- 25047496
TI  - Synergistic association between two alcohol metabolism relevant genes and
      coronary artery disease among Chinese hypertensive patients.
AB  - OBJECTIVE: Coronary artery disease (CAD) is a multifactorial and polygenic
      disease. The aim of this study was to examine the association between six
      polymorphisms of four alcohol metabolism relevant genes (ADH1B, ADH1C, ALDH1b1,
      ALDH2) and the risk of CAD in Han Chinese. METHODS AND RESULTS: This was a
      hospital-based case-control study involving 1365 hypertensive patients. All study
      subjects were angiographically confirmed. Genotypes were determined with ligase
      detection reaction method. There was no observable deviation from the Hardy
      Weinberg equilibrium for six examined polymorphisms in controls. The genotype and
      allele distributions of ALDH1b1 rs2073478 and ALDH2 rs671 polymorphisms differed
      significantly between the two groups (P<=0.005), even after the Bonferroni
      correction. The most common allele combination was A-C-C-G-C-G (alleles in order
      of rs1229984, rs1693482, rs2228093, rs2073478, rs886205, rs671) and its frequency
      was slightly higher in controls than in CAD patients (P = 0.067). After assigning
      the most common allele combination as a reference, allele combination A-C-C-T-C
      A, which simultaneously possessed the risk alleles of rs2073478 and rs671
      polymorphisms, was associated with a 1.80-fold greater risk of CAD. Further, a
      two-locus model including rs2073478 and rs671 that had a maximal testing accuracy
      of 0.598 and a cross-validation consistency of 10 (P = 0.008) was deemed as the
      overall best MDR model, which was further validated by classical Logistic
      regression model. CONCLUSION: Our findings provide clear evidence for both
      individual and interactive associations of ALDH1b1 and ALDH2 genes with the
      development of CAD in Han Chinese.

PMID- 25047498
TI  - Systematic review of tofacitinib: a new drug for the management of rheumatoid
      arthritis.
AB  - PURPOSE: The goal of this study was to review and summarize the efficacy and
      safety of use of tofacitinib for treating rheumatoid arthritis (RA). METHODS: A
      systematic literature review was conducted to identify English-language articles
      published through May 2013 within PubMed, ClinicalTrials.gov, and Cochrane
      Library reporting results from Phase II and Phase III tofacitinib randomized
      clinical trials. Tofacitinib must have been used as monotherapy or in combination
      therapy with disease-modifying antirheumatic drugs (DMARDs) in the treatment of
      RA. Study outcomes had to include at least 1 of the following: American College
      of Rheumatology (ACR) 20%, 50%, or 70% response rates; tender/swollen joint
      count; health assessment questionnaire of disability; radiographic outcomes; and
      drug persistence. FINDINGS: Eight studies (4 Phase II and 4 Phase III trials)
      were included in the review. Patients with active RA and who were nonresponders
      to a biologic agent or the nonbiologic DMARD methotrexate were included in these
      studies. The results of the Phase II trials show that tofacitinib at doses >=3 mg
      BID was efficacious among the nonresponders. The results of the Phase III trials,
      comparing tofacitinib 5 and 10 mg with placebo, show that tofacitinib led to a
      significant improvement in ACR20 response (P < 0.0001), Health Assessment
      Questionnaire-Disability Index (P < 0.0001) scores, and ACR50 response (P <
      0.0001) after 3 months. The efficacy of tofacitinib was numerically similar to
      adalimumab. The most common adverse events were infections, infestations,
      increases in LDL-C and HDL-C levels, and a decrease in neutrophil counts.
      IMPLICATIONS: Tofacitinib is an efficacious drug for the management of moderate
      to severe RA among patients with an inadequate response to methotrexate and tumor
      necrosis factor inhibitors. Long-term studies can help in understanding the
      risk/benefit profile of tofacitinib.

PMID- 25047497
TI  - Effect of ketoconazole on lobeglitazone pharmacokinetics in Korean volunteers.
AB  - PURPOSE: Lobeglitazone, a peroxisome proliferator-activated receptor-gamma
      agonist, is metabolized primarily by the cytochrome P450 (CYP) 3A4 isoenzyme.
      Individuals concomitantly taking lobeglitazone and a CYP3A4 inhibitor may
      experience some adverse effects secondary to increased systemic exposure to
      lobeglitazone. To address such potential concern, we evaluated the effects of
      ketoconazole, a prototypic CYP3A4 inhibitor, on the pharmacokinetic (PK)
      properties and associated adverse effects of lobeglitazone. METHODS: A PK drug
      drug interaction study was conducted in healthy individuals between 20 and 45
      years old in a randomized, open-label, 2-way crossover design. Even though the PK
      study was performed on a single dose of lobeglitazone, multiple ketoconazole
      doses were given to ensure that the full extent of inhibition of CYP3A4 was
      maintained during the PK sampling. All study participants received a single oral
      dose of lobeglitazone 0.5 mg with or without 9 oral 200-mg doses of ketoconazole
      pretreatment twice daily. The primary PK parameter end points (AUC and Cmax) were
      estimated using noncompartmental analysis, and the 90% CIs for the geometric mean
      ratios (ratio of lobeglitazone and ketoconazole to lobeglitazone alone) were
      investigated. Tolerability (adverse events, vital signs, ECG, and laboratory
      tests) was also assessed. FINDINGS: A total of 24 Korean men (mean age, 26 years;
      age range, 20-32 years; mean weight, 68 kg; weight range, 59-81 kg) completed the
      study and were evaluable for lobeglitazone PK properties and tolerability. The
      mean (SD) Cmax values of lobeglitazone with and without ketoconazole were 49 (7)
      ng/mL and 48 (6) ng/mL at 1.5 and 1.0 hours after dosing, respectively. The mean
      (SD) AUCinfinity values were 532 (117) ng.h/mL and 405 (110) ng.h/mL,
      respectively. Although the Cmax was not significantly affected, the geometric
      mean ratio for AUCinfinity was increased by a point estimate of 1.33 (90% CI,
      1.23-1.44). A single oral administration of lobeglitazone 0.5 mg with or without
      ketoconazole pretreatment did not produce any clinically significant adverse
      effects on vital signs, 12-lead ECG profiles, or laboratory tests. IMPLICATIONS:
      The administration of lobeglitazone, 0.5 mg alone or in combination with multiple
      doses of ketoconazole, was generally well tolerated. The systemic exposure of
      lobeglitazone was increased to a modest extent by pretreatment with 9 twice-daily
      doses of ketoconazole. Clinicaltrials.gov identifier: NCT01330563.

PMID- 25047499
TI  - Relations among school/daycare functioning, fear of hypoglycaemia and quality of
      life in parents of young children with type 1 diabetes.
AB  - AIMS AND OBJECTIVES: To investigate the type 1 diabetes-related school/daycare
      experiences of parents of young children and to examine the relationship among
      child school/daycare functioning, parent fear of hypoglycaemia and parent type 1
      diabetes-related quality of life. BACKGROUND: Parents of young children who
      attend school/daycare must rely on others for daily type 1 diabetes management.
      Worry about school/daycare type 1 diabetes management may cause parental distress
      and contribute to diminished parent quality of life. Parental concerns about type
      1 diabetes management in young children in the school/daycare setting have not
      been well described in the literature. DESIGN: Descriptive correlational and
      cross-sectional parent report of questionnaires design. METHODS: As part of a
      randomised controlled trial for parents of young children with type 1 diabetes,
      134 parents completed self-report measures at baseline. Data included
      demographic, school/daycare, and medical information, parent reports of child
      school/daycare functioning, parent fear of hypoglycaemia and parent type 1
      diabetes-related quality of life. RESULTS: Parents of younger children, children
      on a more intensive medical regimen and children who had experienced type 1
      diabetes-related unconsciousness or seizures had more school/daycare concerns.
      Parents who perceived their children had higher school/daycare functioning had
      less fear about hypoglycaemia and reported better type 1 diabetes-related quality
      of life. School/daycare functioning and fear of hypoglycaemia were significantly
      associated with parent type 1 diabetes-related quality of life. CONCLUSIONS:
      Parents' concerns about school/daycare functioning and fear of hypoglycaemia play
      an important role in parents' type 1 diabetes-related quality of life. RELEVANCE
      TO CLINICAL PRACTICE: Members of the healthcare team should be aware of concerns
      related to children attending school/daycare and provide additional support as
      warranted.

PMID- 25047500
TI  - Application of iPS cell technology to cancer epigenome study: uncovering the
      mechanism of cell status conversion for drug resistance in tumor.
AB  - Recent studies imply that cancer cells possess the ability to reversibly change
      their properties between a drug sensitive state and a drug resistant state
      accompanied by epigenetic changes. This evidence indicates that better
      understanding of cancer epigenetics is important for efficient cancer therapies.
      Nevertheless, it had been difficult to deeply examine the epigenetic mechanisms
      because of lack of the tools to actively modify coordinated epigenetic events. In
      this stagnant situation, the reprogramming technology established by Yamanaka and
      coworkers have shed a new light. The novel reprogramming technology has made it
      possible for researchers to artificially introduce epigenetic remodeling into
      somatic cells. Accordingly, we might be able to use this technology as a tool to
      introduce the coordinated epigenetic reorganization. In this review, we introduce
      the idea of cell state interconversion in cancer cells that is attributable to
      altered epigenetic regulations. We then depict the epigenetic modifications
      observed during the process of somatic cell reprogramming and give some examples
      of the difficulty in cancer cell reprogramming. Finally, we discuss how we can
      translate this reprogramming refractoriness of cancer cells into uncovering
      unique epigenetic regulations in cancer cells, which might be applicable
      eventually to the development of novel cancer therapeutics against drug resistant
      cancer cells. 

PMID- 25047501
TI  - Overexpression of miR-17 in gastric cancer is correlated with proliferation
      associated oncogene amplification.
AB  - The molecular mechanism underlying microRNA (miR)-17 overexpression has not been
      clearly evaluated in gastric cancer. We aimed to evaluate the functional roles of
      miR-17 in gastric cancer and test its viability as a therapeutic target. We
      conducted comparative genomic hybridization and expression array analyses on
      human gastric cancer tissue samples, as well as evaluating the functional roles
      of miR-17 in gastric cancer cell lines and transgenic mice. miR-17 overexpression
      in gastric cancer patients was associated with copy number gain of proliferation
      associated oncogenes such as MYC, CCNE1, ERBB2, and FGFR2. Copy number gain of
      MIR17HG gene (13q31.3) was rare, with an overall frequency of 2% in gastric
      cancers (1 of 51). miR-17 knockdown suppressed the monolayer and anchorage
      independent growth of FGFR2-amplified KATO-III gastric cancer cells. mir-17-92
      TG/TG mice overexpressing the mir-17-92 cluster under the villin promoter
      developed spontaneous benign tumors in the intestinal tract (log-rank P for tumor
      free survival = 0.069). Taken together, miR-17 overexpression in gastric cancer
      was rarely associated with MIR17HG gene amplification, but correlated with
      proliferation-associated oncogene amplification. Therefore, miR-17-targeting
      approach may benefit patients with gastric cancers harboring proliferation
      associated oncogene amplification. 

PMID- 25047502
TI  - Feasibility of liver weight estimation by postmortem computed tomography images:
      an autopsy study.
AB  - Although organ weight gives pathologists information about the pathogenesis of
      diseases at autopsy, the knowledge is rarely helpful in postmortem virtual
      autopsy by computed tomography (CT). To investigate the feasibility of liver
      weight estimation based on liver volume estimated from three-dimensional CT
      images and the specific gravity of liver, thirty cadavers who died in the
      University of Fukui Hospital and whose family members agreed to postmortem CT and
      autopsy were prospectively enrolled. Mean specific gravity of liver was 1.054 +/-
      0.009 g/mL (95% confidence interval: 1.0507-1.0573 g/mL). The specific gravity
      was positively correlated to Hounsfield unit (HU) values of less than 40 (cases
      with moderate to severe fatty deposition) and remained stable between 1.05 to
      1.065 g/mL for HU values greater than 40 (cases with mild or no fatty change).
      The liver weight estimated by our formula corresponded well to the actual liver
      weight, and the correlation coefficient was 0.96 (P < 1 * 10(-13) ). The
      estimated liver weight calculated from estimated liver volume and the specific
      gravity of 1.055 g/mL was highly accurate, whereas the specific gravity should be
      reduced by 2%-3% in patients with an HU value less than 40 due to fatty
      deposition. 

PMID- 25047503
TI  - Coronary triglyceride deposition in contemporary advanced diabetics.
AB  - It is of importance to clarify pathophysiology of diabetic heart diseases such as
      heart failure and coronary artery disease. We reported a novel clinical phenotype
      called triglyceride deposit cardiomyovasculopathy (TGCV), showing aberrant TG
      accumulation in both coronary arteries and myocardium, in a cardiac transplant
      recipient. Here, we examined autopsied diabetics for TG deposition in
      cardiovasculature. Consecutive series of hearts from advanced diabetes mellitus
      (DM) subjects (DM group: DMG, n = 20) and those from age- and sex-matched non
      diabetic controls (non DM group: NDMG, n = 20) were examined. The diagnostic
      criteria of 'advanced DM' was made based on 2014 Clinical Practice
      Recommendations proposed by the American Diabetes Association. The mean duration
      of DM was 15.8 years. All DMG suffered from heart diseases including coronary
      artery diseases and 14 subjects had multi-vessel disease. Tissue TG contents were
      measured biochemically. Coronary arterial TG contents was significantly higher in
      DMG compared with NDMG. Spatial distribution of TG in transverse sections of
      coronary arteries showed TG deposition mainly in smooth muscle cells by Imaging
      Mass Spectrometry. Abundant TG deposition in coronary artery might be associated
      with advanced DM. 

PMID- 25047504
TI  - Prognostic significance of CD20 expression and Epstein-Barr virus (EBV)
      association in classical Hodgkin lymphoma in Japan: a clinicopathologic study.
AB  - To investigate the clinicopathological significance of CD20 expression and
      Epstein-Barr virus (EBV) association in Hodgkin and Reed-Sterberg cells of
      classical Hodgkin lymphoma (CHL), CD20 expression and EBV positivity (by EBER in
      situ hybridization) were investigated in 389 CHL patients in Japan. They included
      74 CD20-positive cases (19%) and 315 CD20-negative cases (81%). CD20-positive
      cases showed significantly older age at onset (P = 0.018) and higher association
      with EBV (P = 0.002). Multivariate analysis identified EBV-positivity (but not
      CD20-positivity), presence of B symptoms, thrombocytopenia, elevated serum
      lactate dehydrogenase and performance status >1 as poor prognostic factors for
      overall survival (OS). We constructed a new prognostic model with these five
      factors classifying patients into three groups: low risk, 0-1 adverse factor;
      intermediate risk, 2-3 factors; high risk, 4-5 factors. This prognostic model
      could stratify the prognosis of CHL patients (P < 0.0001). For 144 patients (58%)
      classified into the low-risk group, the 5-year OS was 91%. For 92 patients (37%)
      in the intermediate group, the 5-year OS was 66%; for 11 patients (5%) in the
      high-risk group, the 5-year OS was 36%. In conclusion, EBV is identified as an
      independent poor prognostic factor for CHL patients. Therefore, examination of
      EBV association in CHL is recommended as routine pathologic practice especially
      in countries where EBV infection prevails. 

PMID- 25047505
TI  - Dendritic fibromyxolipoma: a variant of spindle cell lipoma with extensive myxoid
      change, with cytogenetic evidence.
AB  - Dendritic fibromyxolipoma (DFML), a rare, recently described distinct benign soft
      tissue tumor, has many clinicopathological features reminiscent of spindle cell
      lipoma and solitary fibrous tumor with myxoid change. It is distinguished
      histologically from both entities by the presence of spindle and stellate cells
      with dendritic cytoplasmic prolongations, prominent myxoid stroma with abundant
      keloidal collagen and occasional small plexiform vascular proliferation. We
      describe a case of histologically confirmed DFML of the left shoulder in a 67
      year-old male, in which subsequent cytogenetic analysis revealed deletion
      involving 13q14.3 region in all the tumor cells, typically detected in spindle
      cell lipoma. In the presence of many clinicopathological similarities between
      DFML and spindle cell lipoma including chromosomal abnormalities, we postulate
      that DFML is merely a rare variant of spindle cell lipoma with extensive myxoid
      degeneration, and may not be considered as a separate entity. The possible
      differential diagnosis and their distinguishing features are briefly discussed. 

PMID- 25047506
TI  - Ciliated muconodular papillary tumor of the lung: a newly defined peripheral
      pulmonary tumor with conspicuous mucin pool mimicking colloid adenocarcinoma: a
      case report and review of literature.
AB  - We report the case of a 68-year-old man with a newly defined rare entity of a
      peripheral pulmonary tumor, consisting of a nodular papillary lesion with
      papillary structures containing ciliated columnar and goblet cells, as well as
      floating tumor cells in the mucin pool. The conspicuous mucin pool was observed
      to be mimicking colloid adenocarcinoma in a low-power view, particularly in a
      frozen section slide. We originally reported it as an adenocarcinoma during
      intraoperative consultation. Immunohistochemically, the tumor cells exhibited a
      similar immunophenotype to pulmonary adenocarcinoma, except for the presence of
      focal ciliated and basaloid cells, which we found using CK5/6 and P63
      immunostaining. No KRAS or EGFR mutation was found. We revised the diagnosis to
      that of a ciliated muconodular papillary tumor (CMPT). Four years after a wedge
      resection, the patient remained free of tumors. Although the malignant potential
      of CMPT cannot be ignored, a wedge resection with a safe margin might be a
      treatment option for CMPT patients. 

PMID- 25047507
TI  - Malignant pleural mesothelioma mimicking the intrapulmonary growth pattern of
      epithelioid hemangioendothelioma.

PMID- 25047508
TI  - Lymphocytic gastritis showing concomitant occurrence of both CD4 + and CD8 + T
      cells among epithelial cells.

PMID- 25047509
TI  - Measuring physician adherence with gout quality indicators: a role for natural
      language processing.
AB  - OBJECTIVE: To evaluate physician adherence with gout quality indicators (QIs) for
      medication use and monitoring, and behavioral modification (BM). METHODS: Gout
      patients were assessed for the QIs as follows: QI 1: initial allopurinol dosage
      <300 mg/day for patients with chronic kidney disease (CKD); QI 2: uric acid
      within 6 months of allopurinol start; and QI 3: complete blood count and
      creatinine phosphokinase within 6 months of colchicine initiation. Natural
      language processing (NLP) was used to analyze clinical narrative data from
      electronic medical records (EMRs) of overweight (body mass index >=28 kg/m(2) )
      gout patients for BM counseling on gout-specific dietary restrictions, weight
      loss, and alcohol consumption (QI 4). Additional data included sociodemographics,
      comorbidities, and number of rheumatology and primary care visits. QI compliance
      versus noncompliance was compared using chi-square analyses and independent
      groups t-test. RESULTS: In 2,280 gout patients, compliance with QI was as
      follows: QI 1: 92.1%, QI 2: 44.8%, and QI 3: 7.7%. Patients compliant with QI 2
      had more rheumatology visits at 3.5 versus 2.6 visits (P < 0.001), while those
      compliant with QI 3 had more CKD (P < 0.01). Of 1,576 eligible patients, BM
      counseling for weight loss occurred in 1,008 patients (64.0%), low purine diet in
      390 (24.8%), alcohol abstention in 137 (8.7%), and all 3 elements in 51 patients
      (3.2%). Regular rheumatology clinic visits correlated with frequent advice on
      weight loss and gout-specific diet (P < 0.0001). CONCLUSION: Rheumatology clinic
      attendance was associated with greater QI compliance. NLP proved a valuable tool
      for measuring BM as documented in the clinical narrative of EMRs.

PMID- 25047510
TI  - Carbon-encapsulated pyrite as stable and earth-abundant high energy cathode
      material for rechargeable lithium batteries.
AB  - Cathode materials consisting of porous pyrite nano-octahedra encapsulated by
      uniform carbon nanocages exhibit very high energy density, superior rate
      capability (reversible capabilities of 439, 340, and 256 mA h g(-1) at 1C, 2.5C,
      and 5C, respectively) and stable cycling performance (ca. 10% capacity loss after
      50 cycles at 0.5C with a capacity retention of 495 mA h g(-1) ). 

PMID- 25047511
TI  - Identification of inositol 1,4,5-trisphosphate-binding proteins by heparin
      agarose affinity purification and LTQ ORBITRAP MS in Oryza sativa.
AB  - Inositol 1,4,5-trisphosohate (IP3 ) and its receptors play a pivotal role in
      calcium signal transduction in mammals. However, no homologs of mammalian IP3
      receptors have been found in plants. In this study, we isolated the microsomal
      fractions from rice cells in suspension culture and further obtained putative IP3
      -binding proteins by heparin-agarose affinity purification. The IP3 -binding
      activities of these protein fractions were determined by [(3) H] IP3 -binding
      assay. SDS-PAGE and MS analysis were then performed to characterize these
      proteins. We have identified 297 proteins from the eluates of heparin-agarose
      column chromatography, which will provide insight into the IP3 signaling pathways
      in plants. All MS data have been deposited in the ProteomeXchange with identifier
      PXD000763 (http://proteomecentral.proteomexchange.org/dataset/PXD000763). 

PMID- 25047512
TI  - Epigenetic regulation and heart failure.
AB  - Heart failure has become a huge public health problem. The treatment options for
      heart failure, however, are considerably limited. The significant disparity
      between the scope of a prominent health problem and the restricted means of
      therapy propagates heart failure epidemics. Delineating novel mechanisms of heart
      failure is imperative. Emerging evidence suggests that epigenetic regulation may
      take part in the pathogenesis of heart failure. Epigenetic regulation involves
      DNA and histone modifications that lead to changes in DNA-based transcriptional
      programs without altering the DNA sequence. Although more and more mechanisms are
      being discovered, the best understood epigenetic modifications are achieved
      through covalent biochemical reactions including histone acetylation, histone
      methylation and DNA methylation. Connecting environmental stimuli with genomic
      programs, epigenetic regulation remains important in maintaining homeostases and
      the pathogeneses of diseases. This review summarizes the most recent developments
      regarding individual epigenetic modifications and their implications in the
      pathogenesis of heart failure. Understanding this strategically important
      mechanism is potentially the key for developing powerful interventions in the
      future. 

PMID- 25047513
TI  - Correlations between small airway function, ventilation distribution, and
      functional exercise capacity in COPD patients.
AB  - BACKGROUND: Interest in using the nitrogen single-breath washout (N2SBW) test to
      measure ventilation inhomogeneity and small airway function in COPD patients has
      grown in recent years. Our aim was to assess the correlation of the measures
      obtained by the N2SBW test and other pulmonary function parameters with the six
      minute walk distance (6MWD), the degree of dyspnea score, and health status in
      COPD patients. METHODS: In this cross-sectional study, 31 patients with COPD were
      subjected to the N2SBW test, spirometry, whole-body plethysmography, carbon
      monoxide diffusing capacity measurement, the six-minute walk test, the modified
      Medical Research Council (mMRC) scale, and the COPD Assessment Test (CAT).
      RESULTS: We found a strong correlation between the 6MWD and the phase III slope
      of the nitrogen single-breath washout (Phase III slopeN2SBW) (r = -0.796; p =
      0.0001). We found moderate correlations between the 6MWD and the residual volume
      (RV) (r = -0.651; p = 0.0001) and RV/total lung capacity (RV/TLC) (r = -0.600; p
      = 0.0004). We also found moderate correlations between the CAT score and Phase
      III slopeN2SBW(r = 0.728; p = 0.0001), RV (r = 0.646; p = 0.0001) and RV/TLC (r =
      0.603; p = 0.0003). There was a significant difference between the mMRC grades
      for the following variables: Phase III slopeN2SBW (p = 0.0001), RV (p = 0.0001),
      and smoking history (p = 0.008). Multivariate analysis showed that Phase III
      slopeN2SBW was the only independent predictor of the 6MWD (R2 = 0.703; p =
      0.0001), CAT score (R2 = 0.586; p = 0.0001), and mMRC scale (relative risk =
      1.14; p = 0.0001). CONCLUSIONS: In patients with COPD, our findings suggest that
      the ventilation inhomogeneity impacts the functional exercise capacity, the
      degree of dyspnea, and health status.

PMID- 25047514
TI  - Discovery of novel aromatase inhibitors using a homogeneous time-resolved
      fluorescence assay.
AB  - AIM: Aromatase is an important target for drugs to treat hormone-dependent
      diseases, including breast cancer. The aim of this study was to develop a
      homogeneous time-resolved fluorescence (HTRF) aromatase assay suitable for high
      throughput screening (HTS). METHODS: A 384-well aromatase HTRF assay was
      established, and used to screen about 7000 compounds from a compound library.
      Anti-proliferation activity of the hit was evaluated using alamarBlue(R) assay in
      a hormone-dependent breast cancer cell line T47D. Molecular docking was conducted
      to elucidate the binding mode of the hit using the Discovery Studio program.
      RESULTS: The Z' value and signal to background (S/B) ratio were 0.74 and 5.4,
      respectively. Among the 7000 compounds, 4 hits (XHN22, XHN26, XHN27 and
      triptoquinone A) were found to inhibit aromatase with IC50 values of 1.60+/-0.07,
      2.76+/-0.24, 0.81+/-0.08 and 45.8+/-11.3 MUmol /L, respectively. The hits XHN22,
      XHN26 and XHN27 shared the same chemical scaffold of 4-imidazolyl quinoline.
      Moreover, the most potent hit XHN27 at 10 and 50 MUmol/L inhibited the
      proliferation of T47D cells by 45.3% and 35.2%, respectively. The docking study
      revealed that XHN27 docked within the active site of aromatase and might form a
      hydrogen bond and had a pi-cation interaction with amino acid residues of the
      protein. CONCLUSION: XHN27, an imidazolyl quinoline derivative of flavonoid, is a
      potent aromatase inhibitor with anti-proliferation activity against breast cancer
      in vitro. The established assay can be used in HTS for discovering novel
      aromatase inhibitor.

PMID- 25047515
TI  - Therapeutic targeting of SRC kinase in myofibroblast differentiation and
      pulmonary fibrosis.
AB  - Myofibroblasts are effector cells in fibrotic disorders that synthesize and
      remodel the extracellular matrix (ECM). This study investigated the role of the
      Src kinase pathway in myofibroblast activation in vitro and fibrogenesis in vivo.
      The profibrotic cytokine, transforming growth factor beta1 (TGF-beta1), induced
      rapid activation of Src kinase, which led to myofibroblast differentiation of
      human lung fibroblasts. The Src kinase inhibitor AZD0530 (saracatinib) blocked
      TGF-beta1-induced Src kinase activation in a dose-dependent manner. Inhibition of
      Src kinase significantly reduced alpha-smooth muscle actin (alpha-SMA)
      expression, a marker of myofibroblast differentiation, in TGF-beta1-treated lung
      fibroblasts. In addition, the induced expression of collagen and fibronectin and
      three-dimensional collagen gel contraction were also significantly inhibited in
      AZD0530-treated fibroblasts. The therapeutic efficiency of Src kinase inhibition
      in vivo was tested in the bleomycin murine lung fibrosis model. Src kinase
      activation and collagen accumulation were significantly reduced in the lungs of
      AZD0530-treated mice when compared with controls. Furthermore, the total fibrotic
      area and expression of alpha-SMA and ECM proteins were significantly decreased in
      lungs of AZD0530-treated mice. These results indicate that Src kinase promotes
      myofibroblast differentiation and activation of lung fibroblasts. Additionally,
      these studies provide proof-of-concept for targeting the noncanonical TGF-beta
      signaling pathway involving Src kinase as an effective therapeutic strategy for
      lung fibrosis. 

PMID- 25047517
TI  - Pegylation improves the pharmacokinetics and bioavailability of small-molecule
      drugs hydrolyzable by esterases: a study of phospho-Ibuprofen.
AB  - Esterase hydrolysis of drugs can accelerate their elimination, thereby limiting
      their efficacy. Polyethylene glycol (PEG) covalently attached to drugs
      (pegylation) is known to improve the efficiency of many drugs. Using as a test
      agent the novel phospho-ibuprofen (PI), we examined whether pegylation of PI
      could abrogate its hydrolytic degradation by esterases; PI, known to inhibit
      colon cancer growth, has a carboxylic ester hydrolyzable by carboxylesterases
      (CES). We covalently attached mPEG-2000 to PI (PI-PEG) and studied its stability
      by exposing it to cells overexpressing CES and by administering it to mice. We
      also evaluated PI-PEG's anticancer efficacy in human colon cancer xenografts and
      in Apc(min/+) mice. PI-PEG was stable in the presence of cells overexpressing
      CES1 or CES2, whereas PI was extensively hydrolyzed (90.2 +/- 0.7%, 14.3 +/-
      1.1%, mean +/- S.E.M.). In mice, PI was nearly completely hydrolyzed. Intravenous
      administration of PI-PEG resulted in significant levels in blood and in colon
      cancer xenografts (xenograft values in parentheses): area under the curve for 0
      24 hours = 2351 (2621) (nmol/g) * h; Cmax = 1965 (886) nmol/g; Tmax = 0.08 (2)
      hour. The blood levels of ibuprofen, its main hydrolytic product, were minimal.
      Compared with controls, PI-PEG inhibited the growth of the xenografts by 74.8% (P
      < 0.01) and reduced intestinal tumor multiplicity in Apc(min/+) mice by 73.1% (P
      < 0.01), prolonging their survival (100% versus 55.1% of controls; P = 0.013).
      Pegylation protects PI from esterase hydrolysis and improves its
      pharmacokinetics. In preclinical models of colon cancer, PI-PEG is a safe and
      efficacious agent that merits further evaluation. 

PMID- 25047516
TI  - Cyclooxygenase 2 inhibitor celecoxib inhibits glutamate release by attenuating
      the PGE2/EP2 pathway in rat cerebral cortex endings.
AB  - The excitotoxicity caused by excessive glutamate is a critical element in the
      neuropathology of acute and chronic brain disorders. Therefore, inhibition of
      glutamate release is a potentially valuable therapeutic strategy for treating
      these diseases. In this study, we investigated the effect of celecoxib, a
      selective cyclooxygenase-2 (COX-2) inhibitor that reduces the level of
      prostaglandin E2 (PGE2), on endogenous glutamate release in rat cerebral cortex
      nerve terminals (synaptosomes). Celecoxib substantially inhibited the release of
      glutamate induced by the K(+) channel blocker 4-aminopyridine (4-AP), and this
      phenomenon was prevented by chelating the extracellular Ca(2+) ions and by the
      vesicular transporter inhibitor bafilomycin A1. Celecoxib inhibited a 4-AP
      induced increase in cytosolic-free Ca(2+) concentration, and the celecoxib
      mediated inhibition of glutamate release was prevented by the Cav2.2 (N-type) and
      Cav2.1 (P/Q-type) channel blocker omega-conotoxin MVIIC. However, celecoxib did
      not alter 4-AP-mediated depolarization and Na(+) influx. In addition, this
      glutamate release-inhibiting effect of celecoxib was mediated through the PGE2
      subtype 2 receptor (EP2) because it was not observed in the presence of butaprost
      (an EP2 agonist) or PF04418948 [1-(4-fluorobenzoyl)-3-[[6-methoxy-2
      naphthalenyl)methyl]-3-azetidinecarboxylic acid; an EP2 antagonist]. The
      celecoxib effect on 4-AP-induced glutamate release was prevented by the
      inhibition or activation of protein kinase A (PKA), and celecoxib decreased the 4
      AP-induced phosphorylation of PKA. We also determined that COX-2 and the EP2
      receptor are present in presynaptic terminals because they are colocalized with
      synaptophysin, a presynaptic marker. These results collectively indicate that
      celecoxib inhibits glutamate release from nerve terminals by reducing voltage
      dependent Ca(2+) entry through a signaling cascade involving EP2 and PKA. 

PMID- 25047518
TI  - Dual-specificity phosphatase 5 attenuates autoimmune arthritis in mice via
      reciprocal regulation of the Th17/Treg cell balance and inhibition of
      osteoclastogenesis.
AB  - OBJECTIVE: Dual-specificity phosphatase 5 (DUSP-5) is a phosphatase that
      specifically dephosphorylates both phosphoserine and phosphotyrosine residues of
      MAPK. The dysregulated activation of MAPK contributes to the pathogenesis of
      rheumatoid arthritis. This study was undertaken to investigate the therapeutic
      potential of DUSP-5 in preventing the development of autoimmune arthritis in an
      animal model. METHODS: Autoimmune arthritis was induced in DBA/1J mice by
      immunization with type II collagen (CII). Eight days after CII immunization, the
      mice were injected intravenously with pcDNA-DUSP5 or mock vector, and
      electroporation was performed. The serum concentration of anti-CII antibodies was
      measured by enzyme-linked immunosorbent assay. Histologic analysis of the joints
      was performed using Safranin O, toluidine blue, and immunohistochemical staining.
      The expression of transcription factors was analyzed by immunostaining and
      Western blotting. The frequencies of interleukin-17-producing CD4+ Th17 cells and
      CD4+CD25+Foxp3+ Treg cells were analyzed by flow cytometry. RESULTS: In DUSP5
      overexpressing mice, the severity of arthritis, as indicated by the clinical
      arthritis score and the extent of histologic inflammation and cartilage damage,
      was attenuated. The pcDNA-DUSP5-injected mice had lower circulating levels of
      total and CII-specific IgG, IgG1, and IgG2a. The Th17 cell population frequency
      was decreased and the Treg cell frequency was increased in the spleens of the
      DUSP5-treated group. The reciprocal regulation of Th17 and Treg cells in vivo was
      associated with attenuated activity of pSTAT-3 and pERK, and with increased
      activity of pSTAT-5. DUSP5 overexpression suppressed joint damage through down
      regulation of pro-osteoclastogenic molecules. CONCLUSION: The antiarthritic
      properties of DUSP-5 are associated with its reciprocal regulation of Th17 and
      Treg cells and its inhibition of ERK activity.

PMID- 25047519
TI  - Understanding critical barriers to implementing a clinical information system in
      a nursing home through the lens of a socio-technical perspective.
AB  - This paper addresses key barriers to implementing a clinical information system
      (CIS) in a Hong Kong nursing home setting, from a healthcare specific socio
      technical perspective. Data was collected through field observations (n = 12) and
      semi-structured individual interviews (n = 18) of CIS stakeholders in a Hong Kong
      nursing home, and analyzed using the immersion/crystallization approach. Complex
      interactions relevant to our case were contextualized and interpreted within the
      perspective of the Sittig-Singh Healthcare Socio-Technical Framework (HSTF).
      Three broad clusters of implementation barriers from the eight HSTF dimensions
      were identified: (a) Infrastructure-based barriers, which relate to conflict
      between government regulations and system functional needs of users; lack of
      financial support; inconsistency between workflow, work policy, and procedures;
      and inadequacy of hardware-software infrastructural and technical support; (b)
      Process-based barriers, which relate to mismatch between the technology, existing
      work practice and workflow, and communication; low system speed, accessibility,
      and stability; deficient computer literacy; more experience in health care
      profession; clinical content inadequacy and unavailability; as well as poor
      system usefulness and user interface design; and (c) Outcome-based barriers,
      which relate to the lack of measurement and monitoring of system effectiveness.
      Two additional dimensions underlining the importance of the ability of a CIS to
      change are proposed to extend the Sittig-Singh HSTF. First, advocacy would
      promote the articulation and influence of changes in the system and subsequent
      outcomes by CIS stakeholders, and second, adaptability would ensure the ability
      of the system to adjust to emerging needs. The broad set of discovered
      implementation shortcomings expands prior research on why CIS can fail in nursing
      home settings. Moreover, our investigation offers a knowledge base and
      recommendations that can serve as a guide for future implementation strategies
      and policies in CIS initiatives.

PMID- 25047520
TI  - Multi-sources data fusion framework for remote triage prioritization in
      telehealth.
AB  - The healthcare industry is streamlining processes to offer more timely and
      effective services to all patients. Computerized software algorithm and smart
      devices can streamline the relation between users and doctors by providing more
      services inside the healthcare telemonitoring systems. This paper proposes a
      multi-sources framework to support advanced healthcare applications. The proposed
      framework named Multi Sources Healthcare Architecture (MSHA) considers multi
      sources: sensors (ECG, SpO2 and Blood Pressure) and text-based inputs from
      wireless and pervasive devices of Wireless Body Area Network. The proposed
      framework is used to improve the healthcare scalability efficiency by enhancing
      the remote triaging and remote prioritization processes for the patients. The
      proposed framework is also used to provide intelligent services over
      telemonitoring healthcare services systems by using data fusion method and
      prioritization technique. As telemonitoring system consists of three tiers
      (Sensors/ sources, Base station and Server), the simulation of the MSHA algorithm
      in the base station is demonstrated in this paper. The achievement of a high
      level of accuracy in the prioritization and triaging patients remotely, is set to
      be our main goal. Meanwhile, the role of multi sources data fusion in the
      telemonitoring healthcare services systems has been demonstrated. In addition to
      that, we discuss how the proposed framework can be applied in a healthcare
      telemonitoring scenario. Simulation results, for different symptoms relate to
      different emergency levels of heart chronic diseases, demonstrate the superiority
      of our algorithm compared with conventional algorithms in terms of classify and
      prioritize the patients remotely.

PMID- 25047521
TI  - [National S3 guidelines on hepatocellular carcinoma].
AB  - CLINICAL/METHODICAL ISSUE: Evidence-based therapeutic and diagnostic algorithm
      for hepatocellular carcinoma. STANDARD RADIOLOGICAL METHODS: Ultrasound, computed
      tomography, magnetic resonance imaging, image-guided percutaneous biopsy,
      percutaneous thermal ablation and transarterial chemoembolization. METHODICAL
      INNOVATIONS: Diagnostic and therapy of hepatocellular carcinoma according to the
      official German interdisciplinary guidelines. PERFORMANCE: The formulation of the
      German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma was
      performed under special consideration of quality indicators and standardized
      quality improvement methods. ACHIEVEMENTS: In 2013 the German S3 guidelines on
      diagnosis and therapy of hepatocellular carcinoma were published and clinically
      implemented as part of the nationwide guideline program in oncology of the
      Deutsche Krebsgesellschaft (German Cancer Society). PRACTICAL RECOMMENDATIONS:
      The German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma
      have to be considered as the national gold standard with the goal of optimization
      of patient care.

PMID- 25047522
TI  - [Rational imaging of hepatocellular carcinoma. The challenge of multimodal
      diagnostic criteria].
AB  - CLINICAL/METHODICAL ISSUE: Both computed tomography (CT) and magnetic resonance
      imaging (MRI) constitute the gold standard in radiological imaging of
      hepatocellular carcinoma (HCC). In cases of typical contrast behavior each
      modality as a single dynamic technique allows the diagnosis of HCC. There is
      still a challenge in detection of small HCCs < 2 cm, in differentiating HCC and
      high-grade dysplasia from other benign liver lesions as well as the evaluation of
      hypovascular liver lesions in the cirrhotic liver. PERFORMANCE: Nowadays, both
      modalities achieve high detection rates of 90-100 % for lesions > 2 cm. Regarding
      lesions between 1 and 2 cm there is a higher sensitivity for MRI ranging between
      80 and 90 % compared to 60-75 % with CT. Besides the multimodal diagnostic
      criteria, MRI provides significant benefits with the use of hepatobiliary
      contrast. Especially in combination with diffusion- weighted imaging (DWI)
      increased sensitivity and diagnostic accuracy compared to CT has been described
      for lesions sized < 2 cm. Regarding the differentiation from other hepatic
      nodules in the cirrhotic liver there is strong evidence that the coexistence of
      arterial enhancement and hypointensity on hepatobiliary imaging is specific for
      HCC. Moreover, hypointensity on hepatobiliary imaging is associated with a high
      positive predictive value (PPV) of up to 100 % for the presence of high-grade
      dysplasia and HCC. ACHIEVEMENTS: The use of MRI including hepatobiliary imaging
      and DWI has to be regarded as the best non-invasive imaging modality for the
      detection of HCC and for the characterization of nodules in patients with liver
      cirrhosis. In comparison to CT there are benefits regarding detection of small
      lesions < 2 cm and evaluation of hypovascular liver lesions in the context of the
      hepatocarcinogenesis including prognostic values of premalignant lesions.
      PRACTICAL RECOMMENDATIONS: Both MRI and CT provide a high diagnostic performance
      in evaluation of HCC in liver cirrhosis. With MRI there are considerable
      advantages regarding the detection rate and specificity. For daily clinical
      routine, CT offers a fast, reliable and easy available modality with benefits for
      patients in reduced general state of health and restricted compliance.

PMID- 25047523
TI  - [Operative therapy of hepatocellular carcinoma].
AB  - BACKGROUND: Curative surgical strategies for hepatocellular carcinoma are liver
      resection and transplantation. METHODS: This overview is based on a selective
      literature search on therapeutic strategies for hepatocellular carcinoma. The new
      German S3 guidelines are outlined in detail but guidelines from other societies
      were also taken into consideration. RESULTS: The question of resectability is of
      utmost importance and should not only be evaluated in an interdisciplinary tumor
      board but also in an experienced liver center. Primary resectable hepatocellular
      carcinoma in patients without portal hypertension should be resected. Most
      patients without cirrhosis qualify for resection. In patients with Child grade A
      cirrhosis but without severe portal hypertension and a stable health status, a
      liver resection should be considered. At resection intraoperative ultrasound is
      standard. Intrahepatic tumor recurrences also can be re-resected or thermally
      ablated. New techniques for extended liver resections or minimally invasive liver
      resections are commonly used and have to be studied further. CONCLUSION: In
      addition to liver resection, liver transplantation now represents a standard
      therapy for hepatocellular carcinoma in cirrhosis. Observing the Milan selection
      criteria 5-year survival rates of 70-90 % can be achieved; however, increasing
      organ shortage leads to longer waiting times and thus higher risk of tumor
      progression. Therefore, patients on the waiting list should have follow-up
      imaging and bridging with surgical resection, radiofrequency ablation (RFA) or
      transarterial chemoembolization (TACE) by interventional radiology. Living donor
      liver transplantation should be considered in all these patients with expected
      longer waiting times.

PMID- 25047524
TI  - [Transarterial ablative therapy of hepatocellular carcinoma].
AB  - CLINICAL/METHODICAL ISSUE: Due to late diagnosis and a lack of organs only about
      30 % of patients suffering from hepatocellular carcinoma (HCC) undergo curative
      treatment. STANDARD RADIOLOGICAL METHODS: Transarterial chemoembolization (TACE)
      is a routine procedure in intermediate stage HCC. In addition transarterial
      embolization (TAE) and transarterial radioembolization (TARE) are available for
      these patients. PERFORMANCE: For inoperable patients with HCC, TACE is superior
      to best supportive care in terms of survival. Combined with percutaneous ablation
      TACE achieves results similar to resection. ACHIEVEMENTS: Current developments,
      such as drug-eluting beads, TARE and multimodal treatment are well suited to
      further improve outcome in patients with intermediate stage HCC. PRACTICAL
      RECOMMENDATIONS: Transarterial therapies in HCC should be applied in accordance
      with the Barcelona Clinic Liver Cancer (BCLC) criteria. Due to a better safety
      profile and potentially improved disease-free survival the use of drug-eluting
      beads should be liberally considered.

PMID- 25047525
TI  - Pyrosequencing-based analysis of fecal microbial communities in three purebred
      pig lines.
AB  - This study examined the fecal bacterial diversity of 15-week-old pigs from three
      purebred lines: Duroc, Landrace, and Yorkshire. Taxon-dependent and -independent
      analyses were performed to evaluate differences in the fecal bacterial
      communities and to identify bacterial genera that can be used to discriminate
      breeds, following high-throughput pyrosequencing of 16S rRNA genes. Among the
      breeds evaluated, Landrace had the most diverse bacterial community composition.
      Prevotella, Blautia, Oscillibacter, and Clostridium were detected in all samples
      regardless of breed. On the other hand, Catenibacterium, Blautia, Dialister, and
      Sphaerochaeta were differentially detected among breeds, as demonstrated by the
      canonical loading plot. The discriminant analysis of principal components plot
      also showed clear separation of the three purebred pig lines, with a certain
      degree of similarity between Landrace and Yorkshire pigs and a distinct
      separation between Duroc pigs and the other two breeds. Other factors not related
      to breed, such as season or time of sampling and pen effects, may contribute to
      shaping the gut microbiota of pigs.

PMID- 25047529
TI  - Predictive tissue cytometry.

PMID- 25047526
TI  - Drug-induced hyperkalemia.
AB  - Hyperkalemia is a common clinical condition that can be defined as a serum
      potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the
      most important cause of increased potassium levels in everyday clinical practice.
      Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and
      life threatening, posing diagnostic and management problems. A wide range of
      drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with
      potassium homoeostasis either by promoting transcellular potassium shift or by
      impairing renal potassium excretion. Drugs may also increase potassium supply.
      The reduction in renal potassium excretion due to inhibition of the renin
      angiotensin-aldosterone system represents the most important mechanism by which
      drugs are known to cause hyperkalemia. Medications that alter transmembrane
      potassium movement include amino acids, beta-blockers, calcium channel blockers,
      suxamethonium, and mannitol. Drugs that impair renal potassium excretion are
      mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II
      receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs,
      calcineurin inhibitors, heparin and derivatives, aldosterone antagonists,
      potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing
      agents represent another group of medications causing hyperkalemia. Increased
      awareness of drugs that can induce hyperkalemia, and monitoring and prevention
      are key elements for reducing the number of hospital admissions, morbidity, and
      mortality related to drug-induced hyperkalemia. 

PMID- 25047527
TI  - Natural allelic variations in glutathione peroxidase-1 affect its subcellular
      localization and function.
AB  - Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several
      common diseases due to the association between specific allelic variations and
      cancer risk. The most common among these variations are the codon 198
      polymorphism that results in either a leucine or proline and the number of
      alanine repeat codons in the coding sequence. The molecular and biologic
      consequences of these variations remain to be characterized. Toward achieving
      this goal, we have examined the cellular location of GPx-1 encoded by allelic
      variants by ectopically expressing these genes in MCF-7 human breast carcinoma
      cells that produce undetectable levels of GPx-1, thus achieving exclusive
      expression in the same cellular environment. A differential distribution between
      the cytoplasm and mitochondria was observed, with the allele expressing the
      leucine-198 polymorphism and 7 alanine repeats being more cytoplasmically located
      than the other alleles examined. To assess whether the distribution of GPx-1
      between the cytoplasm and mitochondria had a biologic consequence, we engineered
      derivative GPx-1 proteins that were targeted to the mitochondria by the addition
      of a mitochondria targeting sequence and expressed these proteins in MCF-7 cells.
      These cells were examined for their response to oxidative stress, energy
      metabolism, and impact on cancer-associated signaling molecules. The results
      obtained indicated that both primary GPx-1 sequence and cellular location have a
      profound impact on cellular biology and offer feasible hypotheses about how
      expression of distinct GPx-1 alleles can affect cancer risk. Cancer Res; 74(18);
      5118-26. (c)2014 AACR. 

PMID- 25047528
TI  - TLR9 is critical for glioma stem cell maintenance and targeting.
AB  - Understanding supports for cancer stem-like cells in malignant glioma may suggest
      therapeutic strategies for their elimination. Here, we show that the Toll-like
      receptor TLR9 is elevated in glioma stem-like cells (GSC) in which it contributes
      to glioma growth. TLR9 overexpression is regulated by STAT3, which is required
      for GSC maintenance. Stimulation of TLR9 with a CpG ligand (CpG ODN) promoted GSC
      growth, whereas silencing TLR9 expression abrogated GSC development. CpG-ODN
      treatment induced Frizzled4-dependent activation of JAK2, thereby activating
      STAT3. Targeted delivery of siRNA into GSC was achieved via TLR9 using CpG-siRNA
      conjugates. Through local or systemic treatment, administration of CpG-Stat3
      siRNA to silence STAT3 in vivo reduced GSC along with glioma growth. Our findings
      identify TLR9 as a functional marker for GSC and a target for the delivery of
      efficacious therapeutics for glioma treatment. Cancer Res; 74(18); 5218-28.
      (c)2014 AACR. 

PMID- 25047535
TI  - Physicians' attitude toward recurrent hypercalcemia in terminally ill cancer
      patients.
AB  - BACKGROUND: There is no consensus regarding whether cancer-induced hypercalcemia
      should be treated up until the patient's death. The primary aim of this study was
      to clarify physicians' attitude toward treating recurrent hypercalcemia in
      terminally ill cancer patients and associated factors. METHODS: A nationwide,
      cross-sectional survey was performed involving 757 physicians of the Japanese
      Society for Palliative Medicine. Physicians' attitude toward treating
      hypercalcemia in terminally ill patients was assessed based on the response to
      the question: do you agree that you provide medical treatment for recurrent
      hypercalcemia up until a patient's death? As the potential determinants of
      physicians' attitudes, we examined their characteristics, beliefs about
      hypercalcemia, and beliefs about a good death. RESULTS: We obtained a total of
      380 (50.2%) analyzable responses. A total of 163 physicians (43%) agreed that
      hypercalcemia should be treated up until the patient's death, while the remaining
      217 physicians (57%) disagreed. The independent determinants of the attitude
      included the following: physicians' specialty, belief that hypercalcemia
      treatment improves pain, belief that hypercalcemia treatment improves nausea,
      belief that hypercalcemia treatment improves quality of life, belief that
      hypercalcemia treatment prolongs life, belief that the effect of hypercalcemia
      treatment reduces gradually, belief that death with hypercalcemia is less
      distressing, and the perception that being mentally clear is important for a good
      death. CONCLUSION: Japanese physicians had different attitudes toward treating
      hypercalcemia in terminally ill patients. Physicians' beliefs about the efficacy
      of medical treatment for hypercalcemia markedly influenced their attitudes.
      Clarifying evidence on the effect of hypercalcemia treatment on patients'
      symptoms and prognoses is strongly encouraged.

PMID- 25047537
TI  - VapC from the leptospiral VapBC toxin-antitoxin module displays ribonuclease
      activity on the initiator tRNA.
AB  - The prokaryotic ubiquitous Toxin-Antitoxin (TA) operons encode a stable toxin and
      an unstable antitoxin. The most accepted hypothesis of the physiological function
      of the TA system is the reversible cessation of cellular growth under stress
      conditions. The major TA family, VapBC is present in the spirochaete Leptospira
      interrogans. VapBC modules are classified based on the presence of a predicted
      ribonucleasic PIN domain in the VapC toxin. The expression of the leptospiral
      VapC in E. coli promotes a strong bacterial growth arrestment, making it
      difficult to express the recombinant protein. Nevertheless, we showed that long
      term induction of expression in E. coli enabled the recovery of VapC in inclusion
      bodies. The recombinant protein was successfully refolded by high hydrostatic
      pressure, providing a new method to obtain the toxin in a soluble and active
      form. The structural integrity of the recombinant VapB and VapC proteins was
      assessed by circular dichroism spectroscopy. Physical interaction between the
      VapC toxin and the VapB antitoxin was demonstrated in vivo and in vitro by pull
      down and ligand affinity blotting assays, respectively, thereby indicating the
      ultimate mechanism by which the activity of the toxin is regulated in bacteria.
      The predicted model of the leptospiral VapC structure closely matches the
      Shigella's VapC X-ray structure. In agreement, the ribonuclease activity of the
      leptospiral VapC was similar to the activity described for Shigella's VapC, as
      demonstrated by the cleavage of tRNAfMet and by the absence of unspecific
      activity towards E. coli rRNA. This finding suggests that the cleavage of the
      initiator transfer RNA may represent a common mechanism to a larger group of
      bacteria and potentially configures a mechanism of post-transcriptional
      regulation leading to the inhibition of global translation. 

PMID- 25047538
TI  - Fertility studies in female childhood cancer survivors: selecting appropriate
      comparison groups.
AB  - Little information is available on the use of appropriate comparison groups for
      studies investigating late effects of childhood cancer. Two comparison groups in
      a nationwide study on reproductive function and ovarian reserve in female
      childhood cancer survivors were recruited (The Dutch Childhood Oncology Group
      Long-Term Effects After Childhood Cancer Cohort Study). Experiences of this
      process are reported. Two types of comparison groups were used: sisters of
      participating survivors and controls from the general population. A total of 352
      out of 580 (61%) of the participating survivors who had a sister gave permission
      to invite them for the study. The participation rate of sisters was much higher
      than control participants from the general population (74% versus 21%,
      respectively), whereas considerably more effort was involved in recruiting
      controls from the general population. Participants in this group were
      significantly older and more highly educated than sister controls (P < 0.001 for
      both groups). No significant differences were observed between both types of
      comparison groups in several fertility-related characteristics, suggesting
      minimal bias owing to selective participation. Researchers setting up a study to
      investigate late effects among survivors of childhood cancer should carefully
      consider the advantages and disadvantages of using various types of comparison
      groups. 

PMID- 25047539
TI  - Granulosa cells and retinoic acid co-treatment enrich potential germ cells from
      manually selected Oct4-EGFP expressing human embryonic stem cells.
AB  - Differentiation of human embryonic stem (HES) cells to germ cells may become
      clinically useful in overcoming diseases related to germ-cell development. Niches
      were used to differentiate HES cell lines, NTU1 and H9 Oct4-enhanced green
      fluorescence protein (EGFP), including laminin, granulosa cell co-culture or
      conditioned medium, ovarian stromal cell co-culture or conditioned medium,
      retinoic acid, stem cell factor (SCF) and BMP4-BMP7-BMP8b treatment. Flow
      cytometry showed that granulosa cell co-culture (P < 0.001) or conditioned medium
      (P = 0.007) treatment for 14 days significantly increased the percentages of
      differentiated H9 Oct4-EGFP cells expressing early germ cell marker stage
      specific embryonic antigen 1(SSEA1); sorted SSEA1[+] cells did not express higher
      levels of germ cell gene VASA and GDF9. Manually collected H9 Oct4-EGFP[+] cells
      expressed significantly higher levels of VASA (P = 0.005) and GDF9 (P = 0.001).
      H9 Oct4-EGFP[+] cells developed to ovarian follicle-like structures after culture
      for 28 days but with low efficiency. Unlike SCF and BMP4, retinoic acid co
      treatment enhanced VASA, GDF9 and SCP3 expression. A protocol is recommended to
      enrich differentiated HES cells with germ-cell potential by culture with
      granulosa cells, conditioned medium or retinoic acid, manual selection of Oct4
      EGFP[+] cells, and analysis of VASA, GDF9 expression, or both.

PMID- 25047540
TI  - Estimation of copper in saliva and areca nut products and its correlation with
      histological grades of oral submucous fibrosis.
AB  - BACKGROUND: The purpose of this study was to estimate the copper levels in saliva
      of patients with oral submucous fibrosis (OSF) and different areca nut products
      and its correlation with different histological grades of OSF. METHODS: The study
      comprised 60 individuals, 30 OSF patients and 30 non-OSF individuals.
      Unstimulated whole saliva was collected, and copper analysis was performed using
      colorimetric method. The commercial areca nut products used by the patients were
      acquired and subjected to copper analysis through the atomic absorption
      spectrophotometer method. Oral biopsies were performed for OSF patients for
      histopathological correlation. RESULTS: The mean salivary copper level was 27.023
      MUg/dl in OSF patients when compared with 8.393 MUg/dl in non-OSF individuals (P
      < 0.005). The mean copper content in different areca nut products was 13.313 ppm
      (P < 0.005). Comparison of copper content in different areca nut products with
      salivary copper levels of OSF patients showed negative correlation (P < 0.853).
      Comparison of salivary copper levels between different histological grades of OSF
      yielded a statistically significant association between grades I and III (P <
      0.005) and grades II and III OSF (P < 0.019). Comparison of copper content in
      areca nut products and different histological grades of OSF yielded weak negative
      statistical correlation (r = -0.116). CONCLUSION: Despite high copper content in
      areca nut products, the observations yielded a negative correlation with
      different histological grades of OSF. This further raises a doubt about the
      copper content in areca nut as an etiological factor for this crippling disease.

PMID- 25047541
TI  - Comparative ultrasonographic evaluation of the Achilles paratenon in symptomatic
      and asymptomatic subjects: an imaging study.
AB  - Achilles tendon analysis represents one of the most frequently requested
      ultrasonographic evaluations, due to the high incidence of tendinopathy. Various
      authors have described inflammatory features of the paratenon recruited 22
      subjects complaining of pain in the mid-portion of the Achilles tendon and 22
      healthy subjects. Both groups underwent ultrasonographic examination and
      Victorian Institute of Sport Assessment-Achilles questionnaire administration. It
      was found statistically significant inter-group differences of the paratenon (p =
      0.0001) as well as tendon thickness (p < 0.0001). Our results show that Achilles
      symptoms could also be associated with an increase in the paratenon thickness. We
      suggest that clinicians should carefully analyze paratenon thickness when
      evaluating patients with Achillodynia using ultrasound. It may be that the
      paratenon, when thickened, may explain some of the painful symptoms reported by
      patients and it is associated with a tendinopathy process, hence we suggest
      careful analysis in patients with Achillodynia. 

PMID- 25047542
TI  - Three-dimensional reconstruction of the lower limb's venous system in human
      fetuses using the computer-assisted anatomical dissection (CAAD) technique.
AB  - OBJECTIVE: The aim of the present study was to show the feasibility and describe
      the first results of a 3D reconstruction of the venous network of the lower limbs
      in human fetus using the computer-assisted anatomical dissection (CAAD)
      technique. MATERIALS AND METHODS: We used limbs from two human fetuses,
      respectively, 14 and 15 weeks gestation old. Specimens were fixed in 10%
      formalin, embedded in paraffin wax and serially sectioned at 10 m. The
      histological slices were stained using HES and Masson Trichrome for soft tissues
      identification. Immunolabeling techniques using the Protein S-100 marker and the
      D2-40 marker were used to identify nerves and vessels, respectively. Stained
      slices were aligned manually, labeled and digitalized. The segmentation of all
      anatomical structures was achieved using the WinSurf((r)) software after manual
      drawing. RESULTS: A 3D interactive vectorial model of the whole leg, including
      skin, bone, muscles, arteries, veins, and nerves was obtained. In all limbs, we
      observed the presence of a big axial vein traveling along the sciatic nerve. In
      addition, the femoral vein appeared as a small plexus. Although this is a common
      anatomical feature at the end of organogenesis, this feature is observed in only
      9% of adults. Usually interpreted as an "anatomical variation of the femoral
      vein" it should be considered as a light truncular malformation. These
      observations bring further support to our proposed "angio-guiding nerves"
      hypothesis. CONCLUSION: This preliminary study shows that the CAAD technique
      provided an accurate 3D reconstruction of the fetal leg veins anatomy. It should
      bring a new insight for the understanding of the different steps of development
      of the human venous system.

PMID- 25047544
TI  - Commentary on 'A decision aid regarding treatment options for patients with an
      asymptomatic abdominal aortic aneurysm: a randomised clinical trial'.

PMID- 25047545
TI  - Effects of silver nanocolloids on early life stages of the scleractinian coral
      Acropora japonica.
AB  - In this study, the effects of silver nanocolloids (SNCs) on the early life stages
      of the reef-building coral Acropora japonica were investigated. The tolerance of
      this species to SNC contamination was estimated by exposing gametes, larvae, and
      primary polyps to a range of SNC concentrations (0, 0.5, 5, 50, and 500 MUg l(
      1)). Pure SNCs were immediately ionized to Ag(+) in seawater and concentrations
      of >=50 MUg l(-1) SNC had a significant detrimental effect on fertilization,
      larval metamorphosis, and primary polyp growth. Exposure to 50 MUg l(-1) SNC did
      not significantly affect larval survival; however, the larvae were deformed and
      lost their ability to metamorphose. At the highest concentration (500 MUg l(-1)
      SNC), all gametes, larvae, and primary polyps died. These experiments provide the
      first data on the effects of silver-nanomaterial-contaminated seawater on
      cnidarians, and suggest that silver nanomaterials can influence the early
      development of corals through anthropogenic wastewater inputs. 

PMID- 25047546
TI  - Implementation of expert systems to support the functional evaluation of stand-to
      sit activity.
AB  - BACKGROUND: Functional evaluation of sit-to-stand and stand-to-sit activities is
      often used by physiotherapists in patients with neurological and musculoskeletal
      disorders. The observation of the way these activities are executed is essential
      in identifying kinesiological problems. There are different methodologies used to
      describe the stand-to-sit activity and its evaluation is not yet standardized,
      which makes the practical application of resources on clinical observation
      difficult. The objective of this study is to automate the decision making process
      of an evaluation protocol, developed in previous study, and facilitate its
      utilization by professionals in the area. METHODS: A decision-making system has
      been implemented through a computational tool, more specifically an Expert System
      that due its inherent characteristics emulates the decision-making process of a
      human expert in the domain area. A Shell called Expert Sinta was used to develop
      two knowledge bases, i.e. two expert systems, one for the anterior view and
      another for the lateral view of stand-to-sit activity. Variables, values,
      associated rules and confidence factors, objectives, and additional information
      questions were defined by the expert of domain and once implemented each expert
      system generates a number of questions to its user. These questions serve as a
      guide to physiotherapists and support the standardization of the activity
      evaluation. The developed systems were evaluated by physiotherapists through the
      application of a questionnaire that evaluates the knowledge base and the
      usability of the system. The physiotherapists' answers were then evaluated
      through statistical estimation and percentage analysis. RESULTS: When asked about
      the systems' "utility for clinical practice of the physiotherapist", 67% of
      evaluators answered positively. An interesting finding was that most
      physiotherapists (i.e. 92%) considered that the systems are suitable for
      educational purposes, which was not the main objective of this study.
      CONCLUSIONS: The developed expert systems can support the physiotherapist in
      evaluating stand-to-sit activity through a conclusion suggestion about the "level
      of inadequacy" for the "degree of inadequacy" searched during its execution.
      Results of experts' evaluation analyzed through statistical methods indicate that
      the automation of protocols contributed to the standardization of the evaluation
      of stand-to-sit activity and that it has application for teaching purposes.

PMID- 25047547
TI  - Hamstring muscle fatigue and central motor output during a simulated soccer
      match.
AB  - PURPOSE: To examine changes in hamstring muscle fatigue and central motor output
      during a 90-minute simulated soccer match, and the concomitant changes in
      hamstring maximal torque and rate of torque development. METHOD: Eight amateur
      male soccer players performed a 90-minute simulated soccer match, with measures
      performed at the start of and every 15-minutes during each half. Maximal torque
      (Nm) and rate of torque development (RTD; Nm.s-1) were calculated from maximal
      isometric knee flexor contractions performed at 10 degrees  of flexion. Hamstring
      peripheral fatigue was assessed from changes in the size and shape of the resting
      twitch (RT). Hamstring central motor output was quantified from voluntary
      activation (%) and normalized biceps femoris (BF) and medial hamstrings (MH)
      electromyographic amplitudes (EMG/M). RESULTS: Maximal torque was reduced at 45
      minutes by 7.6+/-9.4% (p<0.05). RTD in time intervals of 0-25, 0-50, and 0-75 ms
      post-contraction onset were reduced after 15-minutes in the first-half between
      29.6 to 46.2% (p<0.05), and were further reduced at the end of the second-half
      (p<0.05). Maximal EMG/M was reduced for biceps femoris only concomitant to the
      time-course of reductions in maximal torque (p = 0.007). The rate of EMG rise for
      BF and MH was reduced in early time periods (0-75 ms) post-contraction onset
      (p<0.05). No changes were observed for the size and shape of the RT, indicating
      no hamstring peripheral fatigue. CONCLUSION: Centrally mediated reductions in
      maximal torque and rate of torque development provide insight into factors that
      may explain hamstring injury risk during soccer. Of particular interest were
      early reductions during the first-half of hamstring rate of torque development,
      and the decline in maximal EMG/M of biceps femoris in the latter stages of the
      half. These are important findings that may help explain why the hamstrings are
      particularly vulnerable to strain injury during soccer.

PMID- 25047548
TI  - Effects of rapid cooling prior to freezing on the quality of canine cryopreserved
      spermatozoa.
AB  - The aim of this study was to evaluate the effects of rapid cooling prior to
      freezing on frozen-thawed canine sperm quality. In experiment 1, centrifuged
      ejaculates from 6 dogs were pooled, split into 4 aliquots and cryopreserved by
      the Uppsala procedure using different cooling rates (control, cooling speed 18
      C/90 min and average cooling rate 0.2 C/min; rapid, cooling speed 18 C/8 min and
      average cooling rate 2.25 C/min) in combination with 2 glycerol addition
      protocols (fractionated or unfractionated). In experiment 2, centrifuged
      ejaculates from 4 dogs were processed individually using the same cooling rates
      described in experiment 1 in combination with an unfractionated glycerol addition
      protocol. Each of the experiments was replicated 5 times. Sperm quality was
      evaluated after 30 and 150 min of post-thawing incubation at 38 C. Total motility
      (TM), progressive motility (PM) and quality of movement parameters were assessed
      using a computerized system, and sperm viability (spermatozoa with intact plasma
      and acrosome membranes) was assessed using flow cytometry (H-42/PI/FITC-PNA).
      Values for TM, PM, viable spermatozoa and the quality of movement parameters
      after thawing were not significantly affected by the cooling rate. The
      interaction between the cooling rate and the added glycerol protocol was not
      significant. There were significant differences among the males (P<0.01) in the
      sperm quality parameters evaluated after thawing. The interaction between the
      males and the cooling rate was not significant. In conclusion, canine spermatozoa
      can be cryopreserved using the Uppsala method at an average cooling rate of 2.25
      C/min prior to freezing together with addition of fractionated or unfractionated
      glycerol. 

PMID- 25047549
TI  - Epigenetic modification agents improve genomic methylation reprogramming in
      porcine cloned embryos.
AB  - Incomplete DNA methylation reprogramming in cloned embryos leads to low cloning
      efficiency. Our previous studies showed that the epigenetic modification agents 5
      aza-2'-deoxycytidine (5-aza-dC) or trichostatin A (TSA) could enhance the
      developmental competence of porcine cloned embryos. Here, we investigated genomic
      methylation dynamics and specific gene expression levels during early embryonic
      development in pigs. In this study, our results showed that there was a typical
      wave of DNA demethylation and remethylation of centromeric satellite repeat
      (CenRep) in fertilized embryos, whereas in cloned embryos, delayed demethylation
      and a lack of remethylation were observed. When cloned embryos were treated with
      5-aza-dC or TSA, CenRep methylation reprogramming was improved, and this was
      similar to that detected in fertilized counterparts. Furthermore, we found that
      the epigenetic modification agents, especially TSA, effectively promoted
      silencing of tissue specific genes and transcription of early embryo development
      related genes in porcine cloned embryos. In conclusion, our results showed that
      the epigenetic modification agent 5-aza-dC or TSA could improve genomic
      methylation reprogramming in porcine cloned embryos and regulate the appropriate
      expression levels of genes related to early embryonic development, thereby
      resulting in high developmental competence. 

PMID- 25047550
TI  - Predictors of parent post-traumatic stress symptoms after child hospitalization
      on general pediatric wards: a prospective cohort study.
AB  - OBJECTIVE: The aim of this study was to identify predictors of parental post
      traumatic stress symptoms following child hospitalization. METHODS: In this
      prospective cohort study, a sample of 107 parents completed questionnaires during
      their child's hospitalization on pediatric (non-intensive care) wards and again
      three months after discharge. Eligible parents had a child expected to be
      hospitalized for three or more nights. Standardized questionnaires were used to
      assess parent distress during the child's hospitalization, parent coping
      strategies and resources, and symptoms of post-traumatic stress after the
      hospitalization. Correlations and multiple regressions were used to determine
      whether parent distress during hospitalization and coping strategies and
      resources predicted post-traumatic stress symptoms three months after the child's
      discharge, while controlling for relevant covariates. RESULTS: Three months after
      the child's hospital discharge, 32.7% of parents (n=35) reported some degree of
      post-traumatic stress symptoms, and 21.5% (n=23) had elevated (>=34) scores
      consistent with a probable diagnosis of post-traumatic stress disorder. In the
      multivariable model, parent anxiety and uncertainty during hospitalization and
      use of negative coping strategies, such as denial, venting and self-blame, were
      associated with higher post-traumatic stress symptoms scores at three months post
      discharge, even after controlling for the child's health status. Parental anxiety
      and depression during hospitalization moderated the relationship between negative
      coping strategies and post-traumatic stress symptoms. CONCLUSIONS: More than one
      quarter of parents of children hospitalized on pediatric (non-intensive care)
      wards experienced significant post-traumatic stress symptoms after their child's
      discharge. Parents' hospital-related anxiety, uncertainty and use of negative
      coping strategies are potentially modifiable factors that most strongly
      influenced post-traumatic stress symptoms. Further research is urgently needed to
      test the effectiveness of different methods to provide psychological, emotional
      and instrumental support for parents, focusing on increasing parent coping
      resources and reducing distress during hospitalization.

PMID- 25047543
TI  - Increase in transmitted resistance to non-nucleoside reverse transcriptase
      inhibitors among newly diagnosed HIV-1 infections in Europe.
AB  - BACKGROUND: One out of ten newly diagnosed patients in Europe was infected with a
      virus carrying a drug resistant mutation. We analysed the patterns over time for
      transmitted drug resistance mutations (TDRM) using data from the European Spread
      program. METHODS: Clinical, epidemiological and virological data from 4317
      patients newly diagnosed with HIV-1 infection between 2002 and 2007 were
      analysed. Patients were enrolled using a pre-defined sampling strategy. RESULTS:
      The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8).
      Interestingly, significant changes over time in TDRM caused by the different drug
      classes were found. Whereas nucleoside resistance mutations remained constant at
      5%, a significant decline in protease inhibitors resistance mutations was
      observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance
      to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in
      2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N
      mutation. Phylogenetic analysis showed that these temporal changes could not be
      explained by large clusters of TDRM. CONCLUSION: During the years 2002 to 2007
      transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of
      NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants
      continued monitoring.

PMID- 25047551
TI  - A specialist herbivore uses chemical camouflage to overcome the defenses of an
      ant-plant mutualism.
AB  - Many plants and ants engage in mutualisms where plants provide food and shelter
      to the ants in exchange for protection against herbivores and competitors.
      Although several species of herbivores thwart ant defenses and extract resources
      from the plants, the mechanisms that allow these herbivores to avoid attack are
      poorly understood. The specialist insect herbivore, Piezogaster reclusus
      (Hemiptera: Coreidae), feeds on Neotropical bull-horn acacias (Vachellia
      collinsii) despite the presence of Pseudomyrmex spinicola ants that nest in and
      aggressively defend the trees. We tested three hypotheses for how P. reclusus
      feeds on V. collinsii while avoiding ant attack: (1) chemical camouflage via
      cuticular surface compounds, (2) chemical deterrence via metathoracic defense
      glands, and (3) behavioral traits that reduce ant detection or attack. Our
      results showed that compounds from both P. reclusus cuticles and metathoracic
      glands reduce the number of ant attacks, but only cuticular compounds appear to
      be essential in allowing P. reclusus to feed on bull-horn acacia trees
      undisturbed. In addition, we found that ant attack rates to P. reclusus increased
      significantly when individuals were transferred between P. spinicola ant
      colonies. These results are consistent with the hypothesis that chemical mimicry
      of colony-specific ant or host plant odors plays a key role in allowing P.
      reclusus to circumvent ant defenses and gain access to important resources,
      including food and possibly enemy-free space. This interaction between ants,
      acacias, and their herbivores provides an excellent example of the ability of
      herbivores to adapt to ant defenses of plants and suggests that herbivores may
      play an important role in the evolution and maintenance of mutualisms. 

PMID- 25047552
TI  - The shared mitochondrial genome of Rupicapra pyrenaica ornata and Rupicapra
      rupicapra cartusiana: old remains of a common past.
AB  - Mitochondrial DNA (mtDNA) has largely been used for species delimitation.
      However, mtDNA introgression across species boundaries can lead to inconsistent
      phylogenies. Partial sequences of the mitochondrial genome in the chamois, genus
      Rupicapra, show the presence of three well differentiated clades, West (mtW),
      Central (mtC) and East (mtE), each with a geographically restricted distribution.
      The complete mtDNAs of the clades mtW and mtE (main representatives of the two
      currently considered species R. pyrenaica and R. rupicapra respectively) have
      been reported. In the present study, we sequenced the clade mtC present in
      populations from both species inhabiting the central area of Europe: the
      Apennines (R. pyrenaica ornata) and the Chartreuse Mountains (R. rupicapra
      cartusiana). The phylogenetic comparison with the genomes of Caprini highlights
      the ancient presence of chamois in Europe relative to the fossil record, and the
      old age of the chamois clade mtC that was split from the clade mtW in the early
      Pleistocene. The separation of R. pyrenaica ornata and R. rupicapra cartusiana
      female lineages was recent, dating of the late Pleistocene. Our data represent an
      example of mtDNA introgression of resident females of Chartreuse Mountains into
      immigrant males of R. rupicapra due to male-biased migration and female
      phylopatry. 

PMID- 25047553
TI  - biDCG: a new method for discovering global features of DNA microarray data via an
      iterative re-clustering procedure.
AB  - Biclustering techniques have become very popular in cancer genetics studies, as
      they are tools that are expected to connect phenotypes to genotypes, i.e. to
      identify subgroups of cancer patients based on the fact that they share similar
      gene expression patterns as well as to identify subgroups of genes that are
      specific to these subtypes of cancer and therefore could serve as biomarkers. In
      this paper we propose a new approach for identifying such relationships or
      biclusters between patients and gene expression profiles. This method, named
      biDCG, rests on two key concepts. First, it uses a new clustering technique, DCG
      tree [Fushing et al, PLos One, 8, e56259 (2013)] that generates ultrametric
      topological spaces that capture the geometries of both the patient data set and
      the gene data set. Second, it optimizes the definitions of bicluster membership
      through an iterative two-way reclustering procedure in which patients and genes
      are reclustered in turn, based respectively on subsets of genes and patients
      defined in the previous round. We have validated biDCG on simulated and real
      data. Based on the simulated data we have shown that biDCG compares favorably to
      other biclustering techniques applied to cancer genomics data. The results on the
      real data sets have shown that biDCG is able to retrieve relevant biological
      information. 

PMID- 25047555
TI  - PDT: The plight.

PMID- 25047554
TI  - Moderate-intensity rotating magnetic fields do not affect bone quality and bone
      remodeling in hindlimb suspended rats.
AB  - Abundant evidence has substantiated the positive effects of pulsed
      electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting
      osteopenia and promoting fracture healing. However, the osteogenic potential of
      rotating magnetic fields (RMF), another common electromagnetic application
      modality, remains poorly characterized thus far, although numerous commercial RMF
      treatment devices have been available on the market. Herein the impacts of RMF on
      osteoporotic bone microarchitecture, bone strength and bone metabolism were
      systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month
      old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU
      (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF
      group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging
      from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in
      body mass and soleus muscle mass of rats, which were not obviously altered by
      RMF. Three-point bending test showed that the mechanical properties of femurs in
      HU rats, including maximum load, stiffness, energy absorption and elastic modulus
      were not markedly affected by RMF. uCT analysis demonstrated that 4-week RMF did
      not significantly prevent HU-induced deterioration of femoral trabecular and
      cortical bone microarchitecture. Serum biochemical analysis showed that RMF did
      not significantly change HU-induced decrease in serum bone formation markers and
      increase in bone resorption markers. Bone histomorphometric analysis further
      confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced
      by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and
      osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do
      not significantly affect bone microstructure, bone mechanical strength and bone
      remodeling in HU-induced disuse osteoporotic rats. Our study indicates
      potentially obvious waveform-dependent effects of electromagnetic fields
      stimulated osteogenesis, suggesting that RMF, at least in the present form, might
      not be an optimal modality for inhibiting disuse osteopenia/osteoporosis. 

PMID- 25047556
TI  - Fluorescence induced by aminolevulinic acid and methyl aminolevulinate on normal
      skin.
AB  - BACKGROUND: PDT is a treatment modality, which uses a combination of a
      photosensitising drug, oxygen and light to selectively destroy pre-malignant and
      malignant tissue. The most commonly used PDT photosensitiser precursor is 5
      aminolevulinic acid (ALA). However recently the introduction of methyl
      aminolevulinate (MAL) another topical photosensitiser has posed the question of
      which may be of greater clinical advantage when used in PDT. AIMS: The
      characteristics of PpIX fluorescence following the application of different
      quantities of both ALA and MAL were investigated in normal skin. METHODS: PpIX
      fluorescence was detected using a non-invasive spectroscopy system. A total of 17
      healthy volunteers were recruited, and varying quantities of both ALA and MAL
      were applied to the inner forearm. RESULTS AND CONCLUSIONS: Topical application
      (within the range of 0.01-0.09ml) of both ALA and MAL to normal human skin
      induced PpIX fluorescence. This induced fluorescence was not dose dependent
      within the range investigated. However, the time course and intensity of
      fluorescence was significantly different for ALA and MAL. PpIX-induced
      fluorescence peaked at 7h following the application of MAL, compared to 24h
      following the application of ALA. At all time points, ALA-induced fluorescence
      was significantly greater than that induced by MAL. These results help define
      some of the characteristics of ALA- and MAL-induced PpIX fluorescence in normal
      skin.

PMID- 25047557
TI  - Orthotopic animal models for oncologic photodynamic therapy and photodiagnosis.
AB  - Photodynamic therapy is a complex treatment modality where a large array of
      factors can influence therapeutic outcome. Vascularization, vessel permeability,
      oxygenation and light distribution in the tissue as well as immune response play
      a key role in the photodynamic process. Each of these factors can be influenced
      by the choice of the animal model. It is therefore of the utmost importance to
      choose an appropriate model for pre-clinical oncologic PDT studies. Orthotopic
      tumor models present the closest resemblance to the clinical situation with
      regard to the elements involved in PDT. We present here a brief organ specific
      overview of the different orthotopic animal models that can be used for in vivo
      photodynamic therapy studies. 

PMID- 25047558
TI  - Photodynamic therapy with di-l-arginine protoporphyrinate on WiDr human colon
      adenocarcinoma xenografts in athymic nude mice.
AB  - The fluorescence kinetics of a new photosensitizer for photodynamic therapy, di-l
      arginine protoporphyrinate (PP(Arg)2), was studied in the skin of healthy mice.
      Furthermore, induction of necrosis in WiDr human colon adenocarcinoma xenografts
      in athymic nude mice was studied after photodynamic therapy (PDT) with PP(Arg)2.
      After intravenous administration of PP(Arg)2 maximal fluorescence was reached
      after 72h in normal mouse skin. Complete elimination of the drug from the mouse
      skin was not found even after 32 days. Exposure of WiDr tumours in mice to red
      light (lambda=632nm, fluence 150J/cm(2), fluence rate 250mW/cm(2)) 24 and 72h
      after intravenous administration of 10mg/kg of PP(Arg)2 caused extensive tumour
      necrosis. Epidermal damage and infiltration of inflammatory cells was seen 24h
      after light exposure but not after 72h. 

PMID- 25047559
TI  - Porfimer sodium photodynamic therapy: The long road to acceptance in America.

PMID- 25047560
TI  - Porfimer sodium photodynamic therapy in the treatment of early oesophageal
      carcinoma.
AB  - BACKGROUND: The gold standard treatment of early oesophageal carcinoma is
      oesophagectomy but the elderly population affected are often medically unfit for
      this radical intervention and less invasive curative options are required. We
      describe our experience of porfimer sodium photodynamic therapy (PDT) as an
      alternative to surgery in such a patient group. METHODS: From 1999 to 2005 28
      oesophageal cancer patients were found to have early stage disease based
      initially on endoscopy/CT and latterly on CT/endoscopic ultrasound (EUS)
      criteria. Although potentially suitable for major surgical resection these
      patients were judged to be medically unfit and were selected to have PDT.
      Patients were followed up endoscopically at 6-12-week intervals indefinitely with
      biopsy of the treated area. RESULTS: 18/28 patients had an initial complete
      response 8 weeks post procedure. One patient died before reassessment of
      unrelated disease. Nine patients were non-responders. 7/18 complete responders
      remained disease free for a mean follow up period of 1166 days (249-2019). 11/18
      developed recurrent local disease treated with further PDT with a median survival
      of 770 days (254-2049). Fourteen patients had EUS staging which accurately
      predicted response: all T1N0 patients (9/14) had initial complete response to
      treatment although 5/9 have required further PDT. All remain disease free at a
      follow up of 1103 days (249-2019). No patients with T2/3N0 disease had complete
      response to treatment. The major complication of PDT encountered was stricture
      formation which occurred in 50% of cases and required a median of five dilations
      (range 1-31). CONCLUSIONS: Porfimer sodium PDT is a potentially curative
      treatment in patients with early oesophageal carcinoma who may be unfit or
      unwilling to undergo major surgery.

PMID- 25047561
TI  - The effect of lidocaine on PpIX photobleaching and outcome of ALA-PDT in vitro.
AB  - BACKGROUND: Photodynamic therapy (PDT) is based on the light exposure of
      neoplastic tissue after selective accumulation of photosensitizers in neoplastic
      cells. One of the major side effects of ALA-PDT is pain during light exposure.
      Lidocaine is one of several anaesthetics used to relieve this pain. Although its
      anaesthetic role is well known, it has been proposed that it may act as a
      hydroxyl radical and singlet oxygen scavenger. The effectiveness of PDT is
      directly linked to the yield of singlet oxygen. The aim of this study was to
      investigate possible scavenging properties of lidocaine in photosensitization.
      METHODS: Photodegradation of PpIX in dimethyl sulfoxide (DMSO) solution and in
      WiDr cells alone or in the presence of lidocaine was investigated by fluorescence
      spectroscopy. The influence of lidocaine on PDT outcome was evaluated by
      measuring the colony forming ability of the cells. RESULTS: Lidocaine in DMSO had
      no significant effect (p<0.05) on PpIX photodegradation, although it seems to
      induce a slight increase in the photobleaching rate. The rate of PpIX
      photodegradation and the photosensitivity in cells were similar in the absence
      and in the presence of lidocaine. CONCLUSION: Lidocaine had no significant
      influence on PpIX photobleaching and ALA-PDT outcome in vitro.

PMID- 25047562
TI  - Evaluation of ALA-PDT of ovarian cancer in the Fisher 344 rat tumor model.
AB  - OBJECTIVE: This study aimed to evaluate aminolevulinic acid-photodynamic therapy
      (ALA-PDT) in an experimental tumor model to expand the use of PDT in the
      treatment of ovarian cancer with peritoneal carcinosis. MATERIALS AND METHODS: 5
      Aminolevulinic acid (ALA) (Photocure ASA, Norway) 60mg/kg was injected in the
      peritoneum cavity of 45 female rats Fisher with induced peritoneal metastases of
      ovarian cancer. ALA-PDT was performed 4h later with two different lasers: (1)
      laser diode (Diomed, Cambridge, UK), at 630nm, 100mW/cm(2), or (2) KTP laser
      (Laser Quantum, Stockport, UK), 532nm, 30mW/cm(2). The animals were divided into
      five groups: LASER ALONE group, CTRL group (no cancer), NO LASER group, 1 DOSE
      group (PDT during 1s) and 1.5 DOSE group (PDT during 1.5s). Biopsies were taken
      24h after treatment. A semi-quantitative score called necrosis value (NV) was
      assigned to each sample that reflected the depth of the peritoneal necrosis.
      RESULTS: In the first two groups, the peritoneum remained intact irrespective of
      the wavelength. In the 1 DOSE group, necrosis was observed for 532nm and 630nm.
      In the 1.5 DOSE group, necrosis was observed for 532nm (NV: 3.22+/-0.83) and
      630nm (NV: 2.67+/-1.00) (p<0.05). The mesothelium strongly thinned out in the
      diffuse shape of the tumor. CONCLUSION: Only ALA-PDT induces tumor necrosis with
      either 532nm and 630nm and should be considered an effective therapy for
      micrometastasis of ovarian cancer. This preliminary study deserves further
      experiments.

PMID- 25047564
TI  - Photodynamic therapy using a second generation photosensitizer, Talaporfin.
AB  - BACKGROUND: Photodynamic therapy (PDT) using Talaporfin is an attractive
      treatment for central-type early lung cancer. It was noted that some patients had
      altered levels of arterial oxygen saturation as indicated by pulse oximeter
      (SpO2) and arterial oxygen saturation levels in blood gas analysis (SaO2) during
      PDT. The present experiments were designed to provide an explanation for these
      findings. METHODS: The influence of Talaporfin on SpO2 using in vitro and in vivo
      experiments, and clinically, was examined. RESULTS: Our in vitro and in vivo
      experiments showed a linear relationship between Talaporfin concentration in the
      plasma and the SpO2 level (R=0.9957 and 0.9837). The apparent SpO2 level
      decreased according to the increase of Talaporfin concentration in the plasma. In
      two patients with PDT, SpO2 levels at 4-6h and 24h after Talaporfin
      administration were 93% and 97%, respectively. CONCLUSIONS: Talaporfin raised
      blood absorbance at 660nm with a pulse oximeter. It appeared that the presence of
      the drug falsely decreased the level of SpO2 since SpO2 did not actually change.

PMID- 25047563
TI  - In vitro phototoxicity of glycoconjugated porphyrins and chlorins in colorectal
      adenocarcinoma (HT29) and retinoblastoma (Y79) cell lines.
AB  - BACKGROUND: Retinoblastoma is the most common malignant intraocular tumor in
      children. The current treatment gives a good vital prognostic but there are
      several drawbacks to the arsenal of "classical antitumoral" therapies.
      Photodynamic therapy (PDT) could be an exciting non-toxic and non-mutagenic
      alternative protocol. METHOD: In this paper, we report about the screening of the
      in vitro photocytotoxicity of hydrophenylporphyrins and chlorins and their
      glycoconjugated derivatives in a human retinoblastoma cell line (Y79) and for
      comparison in a colorectal adenocarcinoma cell line (HT29). RESULTS: Despite
      lower photodynamic activity than that observed for hydroxylated photosensitizers,
      in particular Foscan((r)) glycoconjugated derivatives display phototoxicity (IC50
      2.4-0.05MUM +/-10%) against Y79 cells with examples of significant intrinsic
      cytotoxicity. Amongst them the triglucosyl porphyrin 10 is highly photocytotoxic
      (IC50 0.9MUM +/-10%) but is fully devoid of cytotoxicity (IC50>15MUM). The
      photoactivity is highly modulated by the presence of a diethyleneglycol spacer
      between the chromophore and the glycoside (compounds 14-17, IC50 0.5, 0.6, 0.05
      and 0.35MUM +/-10%) and by the anomeric configuration of the sugar (compound 15
      and 17, IC50 0.6 and 0.05MUM +/-10% respectively). One of the main problems for
      the use of Foscan((r)) is its poor solubility which might be improved by
      glycoconjugation. Moreover Foscan has been shown to induce necrosis after PDT
      leading to a possible ulceration of surrounding tissues unsuitable for a
      conservative treatment. A preferential mitochondrial subcellular localization
      which has been previously reported for some glycoconjugated photosensitizers
      could enhance the contribution of apoptosis process. CONCLUSION: Tri-alpha-O
      galactosyl porphyrin 16 is a better candidate than Foscan((r)) for a clinical
      application of PDT for a conservative therapy of retinoblastoma.

PMID- 25047565
TI  - Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures.
AB  - GABAergic interneurons are highly heterogeneous, and much is unknown about the
      specification and functional roles of their neural circuits. Here we show that a
      transinteraction of Elfn1 and mGluR7 controls targeted interneuron synapse
      development and that loss of Elfn1 results in hyperactivity and sensory-triggered
      epileptic seizures in mice. Elfn1 protein increases during postnatal development
      and localizes to postsynaptic sites of somatostatin-containing interneurons (SOM
      INs) in the hippocampal CA1 stratum oriens and dentate gyrus (DG) hilus. Elfn1
      knockout (KO) mice have deficits in mGluR7 recruitment to synaptic sites on SOM
      INs, and presynaptic plasticity is impaired at these synapses. In patients with
      epilepsy and attention deficit hyperactivity disorder (ADHD), we find damaging
      missense mutations of ELFN1 that are clustered in the carboxy-terminal region
      required for mGluR7 recruitment. These results reveal a novel mechanism for
      interneuron subtype-specific neural circuit establishment and define a common
      basis bridging neurological disorders. 

PMID- 25047566
TI  - Combination therapy with silibinin, pegylated interferon and ribavirin in a
      patient with hepatitis C virus genotype 3 reinfection after liver
      transplantation: a case report.
AB  - INTRODUCTION: Hepatitis C virus reinfection occurs universally after liver
      transplantation with accelerated cirrhosis rates of up to 30% within 5 years
      after liver transplantation. Management of hepatitis C virus reinfection is
      complicated by drug interactions and pre-treatment. Dual antiviral therapy with
      pegylated interferon and ribavirin only reaches sustained virological response
      rates of approximately 30% after liver transplantation. With the approval of the
      viral NS3/4A protease and NS5B ribonucleic acid -dependent ribonucleic acid
      polymerase inhibitors, combination therapy offers new therapeutic options
      resulting in considerably higher sustained virological response rates in the non
      transplant setting. However, silibinin has also shown potent antiviral activity
      in non-responders to dual therapy. CASE PRESENTATION: We report the first case of
      antiviral therapy with pegylated interferon and ribavirin in combination with
      silibinin post-liver transplantation in a 50-year-old Caucasian man with genotype
      3 reinfection with prior non-response.Silibinin was administered at a dose of
      20mg/kg/day intravenously for 2 weeks and continued orally for 47 weeks in
      combination with a 48-week pegylated interferon and ribavirin therapy
      (180MUg/week and 800mg/day), which was started on day 8. Pegylated interferon and
      ribavirin doses were adapted to 135MUg/week and 600mg/day. After 4 weeks of
      therapy, the viral load declined 6 log10 and became undetectable in week 6,
      resulting in a sustained virological response 24 weeks after the end of
      therapy.In general, antiviral therapy was well tolerated. Side effects included
      pruritus and anaemia leading to erythropoietin therapy. CONCLUSIONS: Combination
      therapy with pegylated interferon, ribavirin and silibinin resulted in sustained
      virological response 24 weeks after the end of therapy in a patient reinfected
      with hepatitis C virus genotype 3 who was a prior non-responder after liver
      transplantation. Silibinin therapy may offer a new therapeutic option for
      patients reinfected with non-genotype 1 hepatitis C virus who have had a liver
      transplanted and are non-responders.

PMID- 25047567
TI  - Gold-standard and improved framework for sperm head segmentation.
AB  - Semen analysis is the first step in the evaluation of an infertile couple. Within
      this process, an accurate and objective morphological analysis becomes more
      critical as it is based on the correct detection and segmentation of human sperm
      components. In this paper, we present an improved two-stage framework for
      detection and segmentation of human sperm head characteristics (including
      acrosome and nucleus) that uses three different color spaces. The first stage
      detects regions of interest that define sperm heads, using k-means, then
      candidate heads are refined using mathematical morphology. In the second stage,
      we work on each region of interest to segment accurately the sperm head as well
      as nucleus and acrosome, using clustering and histogram statistical analysis
      techniques. Our proposal is also characterized by being fully automatic, where a
      user intervention is not required. Our experimental evaluation shows that our
      proposed method outperforms the state-of-the-art. This is supported by the
      results of different evaluation metrics. In addition, we propose a gold-standard
      built with the cooperation of a referent expert in the field, aiming to compare
      methods for detecting and segmenting sperm cells. Our results achieve notable
      improvement getting above 98% in the sperm head detection process at the expense
      of having significantly fewer false positives obtained by the state-of-the-art
      method. Our results also show an accurate head, acrosome and nucleus segmentation
      achieving over 80% overlapping against hand-segmented gold-standard. Our method
      achieves higher Dice coefficient, lower Hausdorff distance and less dispersion
      with respect to the results achieved by the state-of-the-art method. 

PMID- 25047568
TI  - Proximity to coast is linked to climate change belief.
AB  - Psychologists have examined the many psychological barriers to both climate
      change belief and concern. One barrier is the belief that climate change is too
      uncertain, and likely to happen in distant places and times, to people unlike
      oneself. Related to this perceived psychological distance of climate change,
      studies have shown that direct experience of the effects of climate change
      increases climate change concern. The present study examined the relationship
      between physical proximity to the coastline and climate change belief, as
      proximity may be related to experiencing or anticipating the effects of climate
      change such as sea-level rise. We show, in a national probability sample of 5,815
      New Zealanders, that people living in closer proximity to the shoreline expressed
      greater belief that climate change is real and greater support for government
      regulation of carbon emissions. This proximity effect held when adjusting for
      height above sea level and regional poverty. The model also included individual
      differences in respondents' sex, age, education, political orientation, and
      wealth. The results indicate that physical place plays a role in the
      psychological acceptance of climate change, perhaps because the effects of
      climate change become more concrete and local. 

PMID- 25047570
TI  - The drugs don't work, they just make you worse.

PMID- 25047571
TI  - Anaphylaxis management: a multimodal curriculum with a distinct focus on
      simulation-based training.

PMID- 25047569
TI  - Myocardial infarction is a frequent cause of exercise-related resuscitated out-of
      hospital cardiac arrest in a general non-athletic population.
AB  - BACKGROUND: Performing exercise is shown to prevent cardiovascular disease, but
      the risk of an out-of-hospital cardiac arrest (OHCA) is temporarily increased
      during strenuous activity. We examined the etiology and outcome after
      successfully resuscitated OHCA during exercise in a general non-athletic
      population. METHODS: Consecutive patients with OHCA were admitted with return of
      spontaneous circulation (ROSC) or on-going resuscitation at hospital arrival
      (2002-2011). Patient charts were reviewed for post-resuscitation data. Exercise
      was defined as moderate/vigorous physical activity. RESULTS: A total of 1393 OHCA
      patients were included with 91(7%) arrests occurring during exercise. Exercise
      related OHCA-patients were younger (60 +/- 13 vs. 65 +/- 15, p<0.001) and
      predominantly male (96% vs. 69%, p<0.001). The arrest was more frequently
      witnessed (94% vs. 86%, p=0.02), bystander CPR was more often performed (88% vs.
      54%, p<0.001), time to ROSC was shorter (12 min (IQR: 5-19) vs. 15 (9-22),
      p=0.007) and the primary rhythm was more frequently shock-able (91% vs. 49%,
      p<0.001) compared to non-exercise patients. Cardiac etiology was the predominant
      cause of OHCA in both exercise and non-exercise patients (97% vs. 80%, p<0.001)
      and acute coronary syndrome was more frequent among exercise patients (59% vs.
      38%, p<0.001). One-year mortality was 25% vs. 65% (p<0.001), and exercise was
      even after adjustment associated with a significantly lower mortality (HR=0.40
      (95%CI: 0.23-0.72), p=0.002). CONCLUSIONS: OHCA occurring during exercise was
      associated with a significantly lower mortality in successfully resuscitated
      patients even after adjusting for confounding factors. Acute coronary syndrome
      was more common among exercise-related cardiac arrest patients.

PMID- 25047572
TI  - Treatment of acute left main occlusion by early revascularization combined with
      extracorporeal circulation achieves substantial myocardial salvage as assessed by
      simultaneous positron emission tomography/magnetic resonance imaging.

PMID- 25047573
TI  - Direct qPCR quantification using the Quantifiler((r)) Trio DNA quantification
      kit.
AB  - The effectiveness of a direct quantification assay is essential to the adoption
      of the combined direct quantification/direct STR workflow. In this paper, the
      feasibility of using the Quantifiler((r)) Trio DNA quantification kit for the
      direct quantification of forensic casework samples was investigated. Both low
      level touch DNA samples and blood samples were collected on PE swabs and
      quantified directly. The increased sensitivity of the Quantifiler((r)) Trio kit
      enabled the detection of less than 10pg of DNA in unprocessed touch samples and
      also minimizes the stochastic effect experienced by different targets in the same
      sample. The DNA quantity information obtained from a direct quantification assay
      using the Quantifiler((r)) Trio kit can also be used to accurately estimate the
      optimal input DNA quantity for a direct STR amplification reaction. The
      correlation between the direct quantification results (Quantifiler((r)) Trio kit)
      and the direct STR results (GlobalFilerTM PCR amplification kit(*)) for low-level
      touch DNA samples indicates that direct quantification using the Quantifiler((r))
      Trio DNA quantification kit is more reliable than the Quantifiler((r)) Duo DNA
      quantification kit for predicting the STR results of unprocessed touch DNA
      samples containing less than 10pg of DNA. 

PMID- 25047574
TI  - Effect of probiotics on blood pressure: a systematic review and meta-analysis of
      randomized, controlled trials.
AB  - Previous human clinical trials have shown that probiotic consumption may improve
      blood pressure (BP) control. The aim of the present systematic review was to
      clarify the effects of probiotics on BP using a meta-analysis of randomized,
      controlled trials. PubMed, Scopus, Cochrane Library (Central), Physiotherapy
      Evidence Database, and Clinicaltrial.gov databases were searched until January
      2014 to identify eligible articles. Meta-analysis using a random-effects model
      was chosen to analyze the impact of combined trials. Nine trials were included.
      Probiotic consumption significantly changed systolic BP by -3.56 mm Hg (95%
      confidence interval, -6.46 to -0.66) and diastolic BP by -2.38 mm Hg (95%
      confidence interval, -2.38 to -0.93) compared with control groups. A greater
      reduction was found with multiple as compared with single species of probiotics,
      for both systolic and diastolic BP. Subgroup analysis of trials with baseline BP
      >=130/85 mm Hg compared with <130/85 mm Hg found a more significant improvement
      in diastolic BP. Duration of intervention <8 weeks did not result in a
      significant reduction in systolic or diastolic BP. Furthermore, subgroup analysis
      of trials with daily dose of probiotics <10(11) colony-forming units did not
      result in a significant meta-analysis effect. The present meta-analysis suggests
      that consuming probiotics may improve BP by a modest degree, with a potentially
      greater effect when baseline BP is elevated, multiple species of probiotics are
      consumed, the duration of intervention is >=8 weeks, or daily consumption dose is
      >=10(11) colony-forming units. 

PMID- 25047575
TI  - Urinary potassium excretion and risk of developing hypertension: the prevention
      of renal and vascular end-stage disease study.
AB  - Previous prospective cohort studies on the association between potassium intake
      and risk of hypertension have almost exclusively relied on self-reported dietary
      data, whereas repeated 24-hour urine excretions, as estimate of dietary uptake,
      may provide a more objective and quantitative estimate of this association. Risk
      of hypertension (defined as blood pressure >=140/90 mm Hg or initiation of blood
      pressure-lowering drugs) was prospectively studied in 5511 normotensive subjects
      aged 28 to 75 years not using blood pressure-lowering drugs at baseline of the
      Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Potassium
      excretion was measured in two 24-hour urine specimens at baseline (1997-1998) and
      midway during follow-up (2001-2003). Baseline median potassium excretion was 70
      mmol/24 h (interquartile range, 57-85 mmol/24 h), which corresponds to a dietary
      potassium intake of ~91 mmol/24 h. During a median follow-up of 7.6 years
      (interquartile range, 5.0-9.3 years), 1172 subjects developed hypertension. The
      lowest sex-specific tertile of potassium excretion (men: <68 mmol/24 h; women:
      <58 mmol/24 h) had an increased risk of hypertension after multivariable
      adjustment (hazard ratio, 1.20; 95% confidence interval, 1.05-1.37), compared
      with the upper 2 tertiles (Pnonlinearity=0.008). The proportion of hypertension
      attributable to low potassium excretion was 6.2% (95% confidence interval, 1.7%
      10.9%). No association was found between the sodium to potassium excretion ratio
      and risk of hypertension after multivariable adjustment. Low urinary potassium
      excretion was associated with an increased risk of developing hypertension.
      Dietary strategies to increase potassium intake to the recommended level of 90
      mmol/d may have the potential to reduce the incidence of hypertension. 

PMID- 25047576
TI  - Preserved function of late-outgrowth endothelial cells in medically treated
      hypertensive patients under well-controlled conditions.
AB  - Endothelial progenitor cells (EPCs) participate in renal repair, but their number
      and function may be impaired by exposure to cardiovascular risk factors. The
      number of circulating EPCs is decreased in essential and renovascular
      hypertensive patients, but the effects of hypertension on EPC function are
      incompletely understood. We hypothesized that EPC function was preserved under
      well-controlled conditions in treated hypertensive patients. Patients with
      atherosclerotic renal artery stenosis (ARAS; n=22) or essential hypertension
      (n=24) were studied during controlled sodium intake and antihypertensive regimen.
      Late-outgrowth EPCs were isolated from the inferior vena cava (IVC) and renal
      vein blood of ARAS and essential hypertension patients and a peripheral vein of
      matched normotensive controls (n=18). The angiogenic function of EPCs was
      assessed in vitro, and multidetector computed tomography was used to measure
      single-kidney hemodynamics and function in ARAS and essential hypertension
      patients. Inflammatory biomarkers and EPC homing signal levels and renal release
      were calculated. Inferior vena cava and renal vein-obtained EPC function were
      similar in ARAS and essential hypertension patients and comparable to that in
      normal controls (tube length, 171.86+/-16.846, 191.09+/-14.222, 174.925+/-19.774
      MUm, respectively). Function of renal vein-obtained EPCs directly correlated with
      stenotic kidney glomerular filtration rate, EPC homing factors, and anti
      inflammatory mediator levels in ARAS patients. Therefore, EPC function was
      relatively preserved in ARAS patients, although it directly correlated with renal
      function. Adequate EPC function supports the feasibility of using autologous EPCs
      as a therapeutic option in essential and renovascular hypertensive patients.
      Homing signals and inflammatory mediators may potentially regulate EPC angiogenic
      function. 

PMID- 25047577
TI  - Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell
      transplantation: report of 2 cases.
AB  - BACKGROUND: It is unknown whether the reduction in HIV-1 reservoirs seen after
      allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor
      cells is sufficient to achieve sustained HIV-1 remission. OBJECTIVE: To
      characterize HIV-1 reservoirs in blood and tissues and perform analytic
      antiretroviral treatment interruptions to determine the potential for allogeneic
      HSCT to lead to sustained, antiretroviral-free HIV-1 remission. DESIGN: Case
      report with characterization of HIV-1 reservoirs and immunity before and after
      antiretroviral interruption. SETTING: Tertiary care center. PATIENTS: Two men
      with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors.
      MEASUREMENTS: Quantification of HIV-1 in various tissues after HSCT and the
      duration of antiretroviral-free HIV-1 remission after treatment interruption.
      RESULTS: No HIV-1 was detected from peripheral blood or rectal mucosa before
      analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA
      remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both
      patients experienced rebound viremia within 2 weeks of the most recent negative
      viral load measurement and developed symptoms consistent with the acute
      retroviral syndrome. One patient developed new efavirenz resistance after
      reinitiation of antiretroviral therapy. Reinitiation of active therapy led to
      viral decay and resolution of symptoms in both patients. LIMITATION: The study
      involved only 2 patients. CONCLUSION: Allogeneic HSCT may lead to loss of
      detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral
      free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10
      reduction in reservoir size. Long-lived tissue reservoirs may have contributed to
      viral persistence. The definition of the nature and half-life of such reservoirs
      is essential to achieve durable antiretroviral-free HIV-1 remission. PRIMARY
      FUNDING SOURCE: Foundation for AIDS Research and National Institute of Allergy
      and Infectious Diseases.

PMID- 25047578
TI  - Near-infrared triple-helical peptide with quenched fluorophores for optical
      imaging of MMP-2 and MMP-9 proteolytic activity in vivo.
AB  - The gelatinase members of the MMP family have consistently been associated with
      tumor invasiveness, which make them an attractive target for molecular imaging.
      We report new activatable proteolytic optical imaging agents that consist of
      triple-helical peptide (THP) conjugates, with high specificity to the
      gelatinases, bearing quenched cypate dyes. With quenching efficiencies up to 51%,
      the amplified fluorescence signal upon cypate3-THP hydrolysis by the gelatinases
      (kcat/KM values of 6.4*10(3) M(-1) s(-1) to 9.1*10(3) M(-1) s(-1) for MMP-2 and
      MMP-9, respectively) in mice bearing human fibrosarcoma xenografted tumors was
      monitored with fluorescence molecular tomography. There was significant
      fluorescence enhancement within the tumor and this enhancement was reduced by
      treatment with pan-MMP inhibitor, Ilomastat. These data, combined with the
      gelatinase substrate specificity observed in vitro, indicated the observed
      fluorescence at the site of the tumor was due to gelatinase mediated hydrolysis
      of cypate3-THP.

PMID- 25047579
TI  - Synthesis and binding profile of haloperidol-based bivalent ligands targeting
      dopamine D(2)-like receptors.
AB  - Homodimers of dopamine D2-like receptors are suggested to be of particular
      importance in the pathophysiology of schizophrenia and, thus, serve as promising
      targets for the discovery of atypical antipsychotics. This study describes the
      development of a series of novel bivalent molecules with a pharmacophore derived
      from the dopamine receptor antagonist haloperidol. These dimers were investigated
      in comparison to their monomeric analogues for their D2long, D2short, D3, and D4
      receptor binding and the ability to bridge two neighboring receptor protomers.
      Radioligand binding studies provided diagnostic insights when Hill slopes close
      to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative
      analysis with monovalent control ligands indicated a bivalent binding mode with a
      simultaneous occupancy of two neighboring binding sites. 

PMID- 25047580
TI  - Multifunctional non-viral gene vectors with enhanced stability, improved cellular
      and nuclear uptake capability, and increased transfection efficiency.
AB  - We have developed a new multifunctional, non-viral gene delivery platform
      consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG
      shell for nanoparticle stabilization, poly(gamma-glutamic acid) (gamma-PGA) and
      mTAT (a cell-penetrating peptide) for accelerated cellular uptake, and a nuclear
      localization signal peptide (NLS) for enhanced intracellular transport of DNA to
      the nucleus. In vitro study showed that coating of the binary PPMS/DNA polyplex
      with gamma-PGA promotes cellular uptake of the polyplex particles, particularly
      by gamma-glutamyl transpeptidase (GGT)-positive cells through the GGT-mediated
      endocytosis pathway. Conjugating PEG to the gamma-PGA led to the formation of a
      ternary PPMS/DNA/PGA-g-PEG polyplex with decreased positive charges on the
      surface of the polyplex particles and substantially higher stability in serum
      containing aqueous medium. The cellular uptake rate was further improved by
      incorporating mTAT into the ternary polyplex system. Addition of the NLS peptide
      was designed to facilitate intracellular delivery of the plasmid to the nucleus-
      a rate-limiting step in the gene transfection process. As a result, compared with
      the binary PPMS/LucDNA polyplex, the new mTAT-quaternary PPMS/LucDNA/NLS/PGA-g
      PEG-mTAT system exhibited reduced cytotoxicity, remarkably faster cellular uptake
      rate, and enhanced transport of DNA to the nucleus. All these advantageous
      functionalities contribute to the remarkable gene transfection efficiency of the
      mTAT-quaternary polyplex both in vitro and in vivo, which exceeds that of the
      binary polyplex and commercial LipofectamineTM 2000/DNA lipoplex. The
      multifunctional mTAT-quaternary polyplex system with improved efficiency and
      reduced cytotoxicity represents a new type of promising non-viral vectors for the
      delivery of therapeutic genes to treat tumors.

PMID- 25047581
TI  - Graphene oxide: a new platform for high-performance gas- and liquid-separation
      membranes.

PMID- 25047582
TI  - Herbivores influence the growth, reproduction, and morphology of a widespread
      Arctic willow.
AB  - Shrubs have expanded in Arctic ecosystems over the past century, resulting in
      significant changes to albedo, ecosystem function, and plant community
      composition. Willow and rock ptarmigan (Lagopus lagopus, L. muta) and moose
      (Alces alces) extensively browse Arctic shrubs, and may influence their
      architecture, growth, and reproduction. Furthermore, these herbivores may alter
      forage plants in such a way as to increase the quantity and accessibility of
      their own food source. We estimated the effect of winter browsing by ptarmigan
      and moose on an abundant, early-successional willow (Salix alaxensis) in northern
      Alaska by comparing browsed to unbrowsed branches. Ptarmigan browsed 82-89% of
      willows and removed 30-39% of buds, depending on study area and year. Moose
      browsed 17-44% of willows and browsed 39-55% of shoots. Browsing inhibited apical
      dominance and activated axillary and adventitious buds to produce new vegetative
      shoots. Ptarmigan- and moose-browsed willow branches produced twice the volume of
      shoot growth but significantly fewer catkins the following summer compared with
      unbrowsed willow branches. Shoots on browsed willows were larger and produced 40
      60% more buds compared to unbrowsed shoots. This process of shoot production at
      basal parts of the branch is the mechanism by which willows develop a highly
      complex "broomed" architecture after several years of browsing. Broomed willows
      were shorter and more likely to be re-browsed by ptarmigan, but not moose.
      Ptarmigan likely benefit from the greater quantity and accessibility of buds on
      previously browsed willows and may increase the carrying capacity of their own
      habitat. Despite the observed tolerance of willows to browsing, their vertical
      growth and reproduction were strongly inhibited by moose and ptarmigan. Browsing
      by these herbivores therefore needs to be considered in future models of shrub
      expansion in the Arctic. 

PMID- 25047583
TI  - Novel benzoxazine-based aglycones block glucose uptake in vivo by inhibiting
      glycosidases.
AB  - Glycoside hydrolases catalyze the selective hydrolysis of glycosidic bonds in
      oligosaccharides, polysaccharides, and their conjugates. beta-glucosidases occur
      in all domains of living organisms and constitute a major group among glycoside
      hydrolases. On the other hand, the benzoxazinoids occur in living systems and act
      as stable beta-glucosides, such as 2-(2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin
      3(4H)-one)-beta-D-gluco-pyranose, which hydrolyse to an aglycone DIMBOA. Here, we
      synthesized the library of novel 1,3-benzoxazine scaffold based aglycones by
      using 2-aminobenzyl alcohols and aldehydes from one-pot reaction in a
      chloroacetic acid catalytic system via aerobic oxidative synthesis. Among the
      synthesized benzoxazines, 4-(7-chloro-2,4-dihydro-1H-benzo[d][1,3]oxazin-2
      yl)phenol (compound 7) exhibit significant inhibition towards glucosidase
      compared to acarbose, with a IC50 value of 11.5 uM. Based upon results generated
      by in silico target prediction algorithms (Naive Bayesian classifier), these
      aglycones potentially target the additional sodium/glucose cotransporter 1 (where
      a log likelihood score of 2.70 was observed). Furthermore, the in vitro
      glucosidase activity was correlated with the in silico docking results, with a
      high docking score for the aglycones towards the substrate binding site of
      glycosidase. Evidently, the in vitro and in vivo experiments clearly suggest an
      anti-hyperglycemic effect via glucose uptake inhibition by 4-(7-chloro-2,4
      dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol in the starved rat model. These
      synthetic aglycones could constitute a novel pharmacological approach for the
      treatment, or re-enforcement of existing treatments, of type 2 diabetes and
      associated secondary complications. 

PMID- 25047584
TI  - Chronic venous insufficiency.

PMID- 25047586
TI  - High-resolution color-coded ultrasonography findings of subacute temporal
      arteritis with ulcerating skin lesions.

PMID- 25047588
TI  - Severe tricuspid regurgitation with giant C-v waves after pacer implantation.

PMID- 25047587
TI  - Role of noninvasive testing in the clinical evaluation of women with suspected
      ischemic heart disease: a consensus statement from the American Heart
      Association.

PMID- 25047589
TI  - Cardiology patient page. Tetralogy of Fallot.

PMID- 25047590
TI  - Letter by Andreoletti et al regarding article, "contribution and risks of left
      ventricular endomyocardial biopsy in patients with cardiomyopathies: a
      retrospective study over a 28-year period".

PMID- 25047591
TI  - Response to letter regarding article, "contribution and risk of left ventricular
      endomyocardial biopsy in patients with cardiomyopathies: a retrospective study
      over a 28-year period".

PMID- 25047592
TI  - Rituximab for the treatment of relapses in antineutrophil cytoplasmic antibody
      associated vasculitis.
AB  - OBJECTIVE: Disease relapses are frequent in antineutrophil cytoplasmic antibody
      associated vasculitis (AAV). This study was undertaken to evaluate outcomes in
      patients with AAV who are re-treated with rituximab (RTX) and prednisone for
      severe disease relapses. METHODS: The Rituximab in AAV trial was a randomized,
      double-blind, placebo-controlled trial comparing the rates of remission induction
      among patients treated with RTX (n = 99) and patients treated with
      cyclophosphamide (CYC) followed by azathioprine (AZA) (n = 98). Prednisone was
      tapered to discontinuation after 5.5 months. After remission was achieved,
      patients who experienced a severe disease relapse between months 6 and 18 were
      eligible to receive RTX and prednisone on an open-label basis according to a
      prespecified protocol. Investigators remained blinded with regard to the original
      treatment assignment. RESULTS: Twenty-six patients received RTX for disease
      relapse after remission had initially been achieved with their originally
      assigned treatment. Fifteen of these patients were initially randomized to
      receive RTX and 11 to receive CYC/AZA. Thirteen (87%) of the patients originally
      assigned to receive RTX and 10 (91%) originally assigned to receive CYC/AZA
      achieved remission again with open-label RTX (an overall percentage of 88%). In
      half of the patients treated with open-label RTX, prednisone could be
      discontinued entirely. Patients in this cohort experienced fewer adverse events
      compared to the overall study population (4.7 adverse events per patient-year
      versus 11.8 adverse events per patient-year). CONCLUSION: Re-treatment of AAV
      relapses with RTX and glucocorticoids appears to be a safe and effective
      strategy, regardless of previous treatment.

PMID- 25047594
TI  - [New transparency between physicians and the pharmaceutical industry].
AB  - The long-lasting trusting partnership between physicians and the pharmaceutical
      industry with respect to experience from applied research of medications and
      vocational training, was severely tested by campaign-like dissemination of
      collective accusations of corruption. Instead of standing by their responsibility
      to financing clinical research and vocational training of physicians, the health
      insurance companies in particular claim that physicians are being extensively
      bribed by the pharmaceutical industry. In order to continuously improve the
      mutual targets, i.e. the treatment options for patients, both groups have
      developed transparency regulations. 

PMID- 25047593
TI  - In silico structural homology modelling and docking for assessment of pandemic
      potential of a novel H7N9 influenza virus and its ability to be neutralized by
      existing anti-hemagglutinin antibodies.
AB  - The unpredictable nature of pandemic influenza and difficulties in early
      prediction of pandemic potential of new isolates present a major challenge for
      health planners. Vaccine manufacturers, in particular, are reluctant to commit
      resources to development of a new vaccine until after a pandemic is declared. We
      hypothesized that a structural bioinformatics approach utilising homology-based
      molecular modelling and docking approaches would assist prediction of pandemic
      potential of new influenza strains alongside more traditional laboratory and
      sequence-based methods. The newly emerged Chinese A/Hangzhou/1/2013 (H7N9)
      influenza virus provided a real-life opportunity to test this hypothesis. We used
      sequence data and a homology-based approach to construct a 3D-structural model of
      H7-Hangzhou hemagglutinin (HA) protein. This model was then used to perform
      docking to human and avian sialic acid receptors to assess respective binding
      affinities. The model was also used to perform docking simulations with known
      neutralizing antibodies to assess their ability to neutralize the newly emerged
      virus. The model predicted H7N9 could bind to human sialic acid receptors thereby
      indicating pandemic potential. The model also confirmed that existing antibodies
      against the HA head region are unable to neutralise H7N9 whereas antibodies, e.g.
      Cr9114, targeting the HA stalk region should bind with high affinity to H7N9.
      This indicates that existing stalk antibodies initially raised against H5N1 or
      other influenza A viruses could be therapeutically beneficial in prevention
      and/or treatment of H7N9 infections. The subsequent publication of the H7N9 HA
      crystal structure confirmed the accuracy of our in-silico structural model.
      Antibody docking studies performed using the H7N9 HA crystal structure supported
      the model's prediction that existing stalk antibodies could cross-neutralise the
      H7N9 virus. This study demonstrates the value of using in-silico structural
      modelling approaches to complement physical studies in characterization of new
      influenza viruses. 

PMID- 25047595
TI  - [Delegation yes, substitution no!].
AB  - The aging of society leads on the one hand to increasing case numbers and on the
      other hand to a reduction in the number of physicians available for patient
      treatment. The delegation and substitution of medical duties as a tried and
      tested method is increasingly being recommended in order to compensate for the
      lack of physicians. The Berufsverband der Deutschen Urologen (BDU, Professional
      Association of German Urologists) supports the guiding principle of the
      Bundesarztekammer (Federal Medical Council) of "delegation yes, substitution no"
      and rejects a substitution of medical duties by non-medical academic health
      personnel. Against the background of the demographic changes, the increasing need
      for treatment and the current deficiency of junior physicians, a more extensive
      inclusion of well-qualified and experienced non-medical personnel by the
      delegation of medically responsible duties (medical scope of practice) can be an
      appropriate measure to maintain a good medical service in practices, hospitals
      and nursing homes. 

PMID- 25047596
TI  - [Documentation in outpatient uro-oncology : contribution of the IQUO on quality
      assurance and healthcare research].
AB  - The discussion on the importance of healthcare research and electronic networks
      in urology has taken off again with the topic "uro-cloud". This is a good thing
      but shows that a basic conception is still missing. The Interessenverband zur
      Qualitatssicherung der Arbeit niedergelassener Uro-Onkologen (IQUO, Association
      of Interested Parties on Quality Assurance in the Work of Uro-oncology
      Practitioners) has prematurely recognized the necessity of a standardized
      collation of healthcare data on the treatment of uro-oncological patients in the
      daily routine practice. The aim is to adapt and implement the standards in the
      field of urology. 

PMID- 25047597
TI  - [Claim and reality of selective contact options : experiences in finalizing
      selective contracts in urological care].
AB  - Selective contracts are an important component in addition to the total
      healthcare concept in order to introduce process-related innovations into the
      healthcare system. Since 2011 the Berufsverband der Deutschen Urologen (BDU,
      Professional Association of German Urologists) has held negotiations with
      individual health insurance companies and care providers in order to view
      selective contracts as collective contracts, not only as pilot projects but also
      as additional forms of care.This article illustrates the experiences of the BDU
      in the initiation and finalizing of selective contracts as well as existing weak
      points in the framework conditions. 

PMID- 25047598
TI  - Mexican American adolescents' sleep patterns: contextual correlates and
      implications for health and adjustment in young adulthood.
AB  - Late adolescence is a period of substantial risk for unhealthy sleep patterns.
      This study investigated the contextual correlates and health and adjustment
      implications of sleep patterns among Mexican American youth (N = 246; 51%
      female). We focused on Mexican American youth because they represent a large and
      rapidly increasing subgroup of the US population that is at higher risk for
      health and adjustment problems; this higher risk may be explained, in part, by
      sleep patterns. Using data from seven phone diary interviews conducted when youth
      averaged 18 years of age, we assessed average nighttime sleep duration and night
      to-night variability in sleep duration. Guided by socio-ecological models, we
      first examined how experiences in the family context (time spent and quality of
      relationships with parents, parents' familism values) and in extra-familial
      contexts (school, work, peers) were related to sleep duration and variability.
      The findings revealed that time spent in school, work, and with peers linked to
      less sleep. Further, conflict with mothers was related to greater sleep
      variability. Next, we tested the implications of sleep in late adolescence for
      health (perceived physical health, body mass index) and adjustment (depressive
      symptoms, risky behaviors) in young adulthood. These findings indicated that more
      sleep variability predicted relative decreases in health and increases in risky
      behaviors, and shorter sleep duration predicted relative decreases in poorer
      perceived health for males. The discussion highlights the significance of the
      transition to young adulthood as a target for sleep research and the importance
      of studying sleep within its socio-cultural context.

PMID- 25047599
TI  - Design and effects of supportive followup interventions in clinical care of
      patients with rheumatic diseases: a systematic review with meta-analysis.
AB  - OBJECTIVE: To describe the design and determine the clinical effects of
      supportive followup interventions delivered after or alongside nonsurgical
      treatment or rehabilitation of patients with rheumatic diseases. METHODS: We
      performed a systematic review of randomized controlled trials searching the Ovid
      Medline, Embase, Cinahl, AMED, PsychINFO, and Cochrane Library databases. Trials
      evaluating the effects of interventions designed to enhance and/or prolong the
      effects of rheumatic treatment or rehabilitation were included. Data on pain,
      depression, and physical function were pooled in separate meta-analyses,
      including analyses made to calculate short-term (0-2 months) and long-term (5-6
      months after followup intervention) effects. Risk of bias was assessed by 2
      independent reviewers. RESULTS: The searches generated 3,231 citations, of which
      11 original trials were included. The results demonstrated a great variety in the
      design of followup interventions. We found moderate quality evidence for small
      effects on self-reported physical function, with standardized mean differences of
      -0.15 (95% confidence interval [95% CI] -0.30, 0.00; P = 0.05) at short term, and
      -0.18 (95% CI -0.37, 0.00; P = 0.05) at long-term followup. Moderate quality
      evidence showed no effect of supportive followup interventions on short-term
      depression. Low quality evidence showed no significant effects on short-term
      pain, and very low quality evidence showed no significant effects on long-term
      pain and depression. CONCLUSION: Currently there is no clear evidence concerning
      what constitutes an optimal design of supportive followup interventions. There is
      evidence that supportive followup can improve physical function in patients with
      rheumatic diseases, whereas no significant effects were found for pain and
      depression.

PMID- 25047600
TI  - Clinical phenotype-based gene prioritization: an initial study using semantic
      similarity and the human phenotype ontology.
AB  - BACKGROUND: Exome sequencing is a promising method for diagnosing patients with a
      complex phenotype. However, variant interpretation relative to patient phenotype
      can be challenging in some scenarios, particularly clinical assessment of rare
      complex phenotypes. Each patient's sequence reveals many possibly damaging
      variants that must be individually assessed to establish clear association with
      patient phenotype. To assist interpretation, we implemented an algorithm that
      ranks a given set of genes relative to patient phenotype. The algorithm orders
      genes by the semantic similarity computed between phenotypic descriptors
      associated with each gene and those describing the patient. Phenotypic descriptor
      terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity
      is derived from each term's information content. RESULTS: Model validation was
      performed via simulation and with clinical data. We simulated 33 Mendelian
      diseases with 100 patients per disease. We modeled clinical conditions by adding
      noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms
      less specific than the actual disease terms. We ranked the causative gene against
      all 2488 HPO annotated genes. The median causative gene rank was 1 for the
      optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision
      with noise case. Additionally, we examined a clinical cohort of subjects with
      hearing impairment. The disease gene median rank was 22. However, when also
      considering the patient's exome data and filtering non-exomic and common
      variants, the median rank improved to 3. CONCLUSIONS: Semantic similarity can
      rank a causative gene highly within a gene list relative to patient phenotype
      characteristics, provided that imprecision is mitigated. The clinical case
      results suggest that phenotype rank combined with variant analysis provides
      significant improvement over the individual approaches. We expect that this
      combined prioritization approach may increase accuracy and decrease effort for
      clinical genetic diagnosis.

PMID- 25047601
TI  - Using genotyping-by-sequencing (GBS) for genomic discovery in cultivated oat.
AB  - Advances in next-generation sequencing offer high-throughput and cost-effective
      genotyping alternatives, including genotyping-by-sequencing (GBS). Results have
      shown that this methodology is efficient for genotyping a variety of species,
      including those with complex genomes. To assess the utility of GBS in cultivated
      hexaploid oat (Avena sativa L.), seven bi-parental mapping populations and
      diverse inbred lines from breeding programs around the world were studied. We
      examined technical factors that influence GBS SNP calls, established a workflow
      that combines two bioinformatics pipelines for GBS SNP calling, and provided a
      nomenclature for oat GBS loci. The high-throughput GBS system enabled us to place
      45,117 loci on an oat consensus map, thus establishing a positional reference for
      further genomic studies. Using the diversity lines, we estimated that a minimum
      density of one marker per 2 to 2.8 cM would be required for genome-wide
      association studies (GWAS), and GBS markers met this density requirement in most
      chromosome regions. We also demonstrated the utility of GBS in additional
      diagnostic applications related to oat breeding. We conclude that GBS is a
      powerful and useful approach, which will have many additional applications in oat
      breeding and genomic studies. 

PMID- 25047602
TI  - Female sex is associated with worse prognosis in patients with hypertrophic
      cardiomyopathy in China.
AB  - BACKGROUND: Sex plays an important role in the clinical expression and prognosis
      of various cardiovascular diseases. This study was designed to observe the
      effects of sex on hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: A total
      of 621 unrelated patients with HCM without heart failure (460 males) were
      enrolled from 1999 to 2011. Compared to male patients, at baseline female
      patients were older at diagnosis (49.6+/-17.2 years vs. 46.7+/-14.4 years, P =
      0.033), and had greater frequency of left ventricular outflow tract obstruction
      (72/161, 44.7% vs. 149/460, 32.4%, P = 0.005). During the average four year
      follow-up period (range 2-7 years), survival analysis showed that the incidences
      of mortality from all causes, cardiovascular death and progression to chronic
      heart failure were greater in women than in men (P = 0.031, 0.040 and 0.012,
      respectively). After adjustment for multiple factors that may confound survival
      and cardiac function, female sex remained an independent risk factor for all
      cause mortality, cardiovascular death, and chronic heart failure [hazard ratio
      (HR) 2.19, 95% confidence interval (CI) 1.21-3.95, P = 0.010; HR 2.19, 95% CI
      1.17-4.09, P = 0.014; HR 1.73, 95% CI 1.12-2.69, P = 0.014, respectively] in HCM
      patients. Subgroup analysis revealed that female sex as a risk factor was
      identified only in patients younger than 50 years old (P = 0.011, 0.011 and
      0.009, respectively), but not for those 50 years or older. CONCLUSION: Our
      results suggest that female sex is associated with worse survival and heart
      failure in HCM patients. Further studies are required to determine whether female
      hormones modify the clinical expression and prognosis of HCM.

PMID- 25047603
TI  - Medicinal herbs and methodologies for their pharmaceutical compounding in the
      West Bank/Palestine.
AB  - This study focused on herbalists, herbal shops and people currently using
      traditional Arabic medicine. Informants were asked to list plants and methods for
      obtaining plant herbal extracts used to manage a range of illnesses. A total of
      109 plants were identified, of these, principle plant elements included, leaves
      (47.3%), fruits (18.5%) and seeds (18.0%) were most commonly utilized. Extraction
      methods included decoction (boiling) 51%, and infusion 17% and prepared as
      creams, powders, syrups, food or cooked. Many plant species are used by
      herbalists for treating a range of ailments. This study suggests that a lack of
      methodological standardization during herbal extraction could compromise herbal
      stability. There is also a need to monitor for potential adverse drug
      interactions when used concurrently with prescribed medications. 

PMID- 25047604
TI  - Why do psychotherapists participate in psychotherapy research and why not?
      Results of the Attitudes to Psychotherapy Research Questionnaire with a sample of
      experienced German psychotherapists.
AB  - OBJECTIVE: Psychotherapy research needs to convince psychotherapists to
      contribute their time and effort to participate. The present paper describes the
      development and first results of the Attitudes to Psychotherapy Research
      Questionnaire (APRQ). METHOD: The APRQ and additional qualitative questions about
      exclusion criteria for participation were filled out by a sample of 365
      therapists (psychoanalytic, psychodynamic, and cognitive-behavioral) during an
      Internet-based research survey. RESULTS: A principle component analysis yielded
      six factors: Benefits, Damage, Legitimation, Self-doubt, Effectiveness Doubt and
      External Reasons. Age, external reasons and benefits predicted willingness to
      participate independent of therapeutic school. DISCUSSION: Results show a
      changing trend to more positive attitudes to psychotherapy research. To be
      willing to participate in future research, therapists expected high quality
      designs, financial compensation, and personal gains.

PMID- 25047605
TI  - Illness perception in people with chronic obstructive pulmonary disease.
AB  - Illness perception (IP) concerns how patients evaluate living with a disease. To
      get a broader understanding of IP in patients with chronic obstructive pulmonary
      disease (COPD), we investigated whether breathlessness is an important precursor
      of IP and whether IP in its turn is related to mental health, physical health and
      global quality of life (QOL). One hundred and fifty-four patients with COPD
      participated in a cross-sectional survey. Participants underwent pulmonary
      function testing, provided socio-demographic and clinical information, and
      completed the following standardized instruments: Brief Illness Perception
      Questionnaire, Respiratory Quality of Life Questionnaire, Short-Form 12 Health
      Survey and the Quality of Life Scale. Multiple regression analyses were
      performed. A high IP score indicates that a patient believes that his/her illness
      represents a threat. Participants with a high score on the IP dimensions
      consequences, identity, concern and emotional representation, experienced more
      breathlessness. High scores on the IP dimensions consequences, identity and
      concern were associated with impaired physical health and high scores on the IP
      dimensions consequences, identity and emotional representation were associated
      with impaired mental health. Impaired global QOL was associated with high scores
      on the IP dimensions consequences, identity, concern, coherence and emotional
      representation. The strength of the associations between breathlessness and
      physical/mental health and global QOL decreased when certain dimensions of IP
      were included as predictors, indicating that IP to some extent acts as a
      mediating factor. These findings may have practical implications of patient
      counselling by helping COPD patients to cope with their disease by restructuring
      their personal models of illness. 

PMID- 25047606
TI  - Centrosomes back in the limelight.

PMID- 25047607
TI  - Exploring the evolutionary history of centrosomes.
AB  - The centrosome is the main organizer of the microtubule cytoskeleton in animals,
      higher fungi and several other eukaryotic lineages. Centrosomes are usually
      located at the centre of cell in tight association with the nuclear envelope and
      duplicate at each cell cycle. Despite a great structural diversity between the
      different types of centrosomes, they are functionally equivalent and share at
      least some of their molecular components. In this paper, we explore the
      evolutionary origin of the different centrosomes, in an attempt to understand
      whether they are derived from an ancestral centrosome or evolved independently
      from the motile apparatus of distinct flagellated ancestors. We then discuss the
      evolution of centrosome structure and function within the animal lineage. 

PMID- 25047608
TI  - Organization of early frog embryos by chemical waves emanating from centrosomes.
AB  - The large cells in early vertebrate development face an extreme physical
      challenge in organizing their cytoplasm. For example, amphibian embryos have to
      divide cytoplasm that spans hundreds of micrometres every 30 min according to a
      precise geometry, a remarkable accomplishment given the extreme difference
      between molecular and cellular scales in this system. How do the biochemical
      reactions occurring at the molecular scale lead to this emergent behaviour of the
      cell as a whole? Based on recent findings, we propose that the centrosome plays a
      crucial role by initiating two autocatalytic reactions that travel across the
      large cytoplasm as chemical waves. Waves of mitotic entry and exit propagate out
      from centrosomes using the Cdk1 oscillator to coordinate the timing of cell
      division. Waves of microtubule-stimulated microtubule nucleation propagate out to
      assemble large asters that position spindles for the following mitosis and
      establish cleavage plane geometry. By initiating these chemical waves, the
      centrosome rapidly organizes the large cytoplasm during the short embryonic cell
      cycle, which would be impossible using more conventional mechanisms such as
      diffusion or nucleation by structural templating. Large embryo cells provide
      valuable insights to how cells control chemical waves, which may be a general
      principle for cytoplasmic organization. 

PMID- 25047609
TI  - One to only two: a short history of the centrosome and its duplication.
AB  - This review discusses some of the history of the fundamental, but not fully
      solved problem of how the centrosome duplicates from one to only two as the cell
      prepares for mitosis. We start with some of the early descriptions of the
      centrosome and the remarkably prescient but then controversial inferences drawn
      concerning its function in the cell. For more than 100 years, one of the most
      difficult issues for the concept of the centrosome has been to integrate
      observations that centrosomes appear to be important for spindle assembly in
      animal cells yet are not evident in higher plant cells and some animal cells.
      This stirred debate over the existence of centrosomes and their importance. A
      parallel debate concerned the role of the centrioles in organizing centrosomes.
      The relatively recent elucidation of bipolar spindle assembly around chromatin
      allows a re-examination of the role of centrioles in controlling centrosome
      duplication in animal cells. The problem of how centrosomes precisely double in
      preparation for mitosis in animal cells has now moved to the mystery of how only
      one procentriole is assembled at each mother centriole. 

PMID- 25047610
TI  - Lessons from yeast: the spindle pole body and the centrosome.
AB  - The yeast spindle pole body (SPB) is the functional equivalent of the centrosome.
      Most SPB components have been identified and their functions partly established.
      This involved a large variety of techniques which are described here, and the
      potential use of some of these in the centrosome field is highlighted. In
      particular, very useful structural information on the SPB was obtained from a
      reconstituted complex, the gamma-tubulin complex, and also from a sub-particle,
      SPB cores, prepared by extraction of an enriched SPB preparation. The labelling
      of SPB proteins with GFP at the N or C termini, using GFP tags inserted into the
      genome, gave informative electron microscopy localization and fluorescence
      resonance energy transfer data. Examples are given of more precise functional
      data obtained by removing domains from one SPB protein, Spc110p, without
      affecting its essential function. Finally, a structural model for SPB duplication
      is described and the differences between SPB and centrosome duplication
      discussed.

PMID- 25047611
TI  - Centriole structure.
AB  - Centrioles are among the largest protein-based structures found in most cell
      types, measuring approximately 250 nm in diameter and approximately 500 nm long
      in vertebrate cells. Here, we briefly review ultrastructural observations about
      centrioles and associated structures. At the core of most centrioles is a
      microtubule scaffold formed from a radial array of nine triplet microtubules.
      Beyond the microtubule triplets of the centriole, we discuss the critically
      important cartwheel structure and the more enigmatic luminal density, both found
      on the inside of the centriole. Finally, we discuss the connectors between
      centrioles, and the distal and subdistal appendages outside of the microtubule
      scaffold that reflect centriole age and impart special functions to the
      centriole. Most of the work we review has been done with electron microscopy or
      electron tomography of resin-embedded samples, but we also highlight recent work
      performed with cryoelectron microscopy, cryotomography and subvolume averaging.
      Significant opportunities remain in the description of centriolar structure, both
      in mapping of component proteins within the structure and in determining the
      effect of mutations on components that contribute to the structure and function
      of the centriole. 

PMID- 25047612
TI  - Cartwheel assembly.
AB  - The cartwheel is a subcentriolar structure consisting of a central hub and nine
      radially arranged spokes, located at the proximal end of the centriole. It
      appears at the initial stage of the centriole assembly process as the first
      ninefold symmetrical structure. The cartwheel was first described more than 50
      years ago, but it is only recently that its pivotal role in establishing the
      ninefold symmetry of the centriole was demonstrated. Significant progress has
      since been made in understanding its fine structure and assembly mechanism. Most
      importantly, the central part of the cartwheel, from which the ninefold symmetry
      originates, is shown to form by self-association of nine dimers of the protein
      SAS-6. This finding, together with emerging data on other components of the
      cartwheel, has opened new avenues in centrosome biology.

PMID- 25047613
TI  - Pericentriolar material structure and dynamics.
AB  - A centrosome consists of two barrel-shaped centrioles embedded in a matrix of
      proteins known as the pericentriolar material (PCM). The PCM serves as a platform
      for protein complexes that regulate organelle trafficking, protein degradation
      and spindle assembly. Perhaps most important for cell division, the PCM
      concentrates tubulin and serves as the primary organizing centre for microtubules
      in metazoan somatic cells. Thus, similar to other well-described organelles, such
      as the nucleus and mitochondria, the cell has compartmentalized a multitude of
      vital biochemical reactions in the PCM. However, unlike these other organelles,
      the PCM is not membrane bound, but rather a dynamic collection of protein
      complexes and nucleic acids that constitute the organelle's interior and
      determine its boundary. How is the complex biochemical machinery necessary for
      the myriad centrosome functions concentrated and maintained in the PCM? Recent
      advances in proteomics and RNAi screening have unveiled most of the key PCM
      components and hinted at their molecular interactions ( table 1). Now we must
      understand how the interactions between these molecules contribute to the
      mesoscale organization and the assembly of the centrosome. Among outstanding
      questions are the intrinsic mechanisms that determine PCM shape and size, and how
      it functions as a biochemical reaction hub. 

PMID- 25047614
TI  - The centriole duplication cycle.
AB  - Centrosomes are the main microtubule-organizing centre of animal cells and are
      important for many critical cellular and developmental processes from cell
      polarization to cell division. At the core of the centrosome are centrioles,
      which recruit pericentriolar material to form the centrosome and act as basal
      bodies to nucleate formation of cilia and flagella. Defects in centriole
      structure, function and number are associated with a variety of human diseases,
      including cancer, brain diseases and ciliopathies. In this review, we discuss
      recent advances in our understanding of how new centrioles are assembled and how
      centriole number is controlled. We propose a general model for centriole
      duplication control in which cooperative binding of duplication factors defines a
      centriole 'origin of duplication' that initiates duplication, and passage through
      mitosis effects changes that license the centriole for a new round of duplication
      in the next cell cycle. We also focus on variations on the general theme in which
      many centrioles are created in a single cell cycle, including the specialized
      structures associated with these variations, the deuterosome in animal cells and
      the blepharoplast in lower plant cells. 

PMID- 25047615
TI  - Separate to operate: control of centrosome positioning and separation.
AB  - The centrosome is the main microtubule (MT)-organizing centre of animal cells. It
      consists of two centrioles and a multi-layered proteinaceous structure that
      surrounds the centrioles, the so-called pericentriolar material. Centrosomes
      promote de novo assembly of MTs and thus play important roles in Golgi
      organization, cell polarity, cell motility and the organization of the mitotic
      spindle. To execute these functions, centrosomes have to adopt particular
      cellular positions. Actin and MT networks and the association of the centrosomes
      to the nuclear envelope define the correct positioning of the centrosomes.
      Another important feature of centrosomes is the centrosomal linker that connects
      the two centrosomes. The centrosome linker assembles in late mitosis/G1
      simultaneously with centriole disengagement and is dissolved before or at the
      beginning of mitosis. Linker dissolution is important for mitotic spindle
      formation, and its cell cycle timing has profound influences on the execution of
      mitosis and proficiency of chromosome segregation. In this review, we will focus
      on the mechanisms of centrosome positioning and separation, and describe their
      functions and mechanisms in the light of recent findings. 

PMID- 25047616
TI  - The centrosome-Golgi apparatus nexus.
AB  - A shared feature among all microtubule (MT)-dependent processes is the
      requirement for MTs to be organized in arrays of defined geometry. At a
      fundamental level, this is achieved by precisely controlling the timing and
      localization of the nucleation events that give rise to new MTs. To this end, MT
      nucleation is restricted to specific subcellular sites called MT-organizing
      centres. The primary MT-organizing centre in proliferating animal cells is the
      centrosome. However, the discovery of MT nucleation capacity of the Golgi
      apparatus (GA) has substantially changed our understanding of MT network
      organization in interphase cells. Interestingly, MT nucleation at the Golgi
      apparently relies on multiprotein complexes, similar to those present at the
      centrosome, that assemble at the cis-face of the organelle. In this process,
      AKAP450 plays a central role, acting as a scaffold to recruit other centrosomal
      proteins important for MT generation. MT arrays derived from either the
      centrosome or the GA differ in their geometry, probably reflecting their
      different, yet complementary, functions. Here, I review our current understanding
      of the molecular mechanisms involved in MT nucleation at the GA and how Golgi-
      and centrosome-based MT arrays work in concert to ensure the formation of a
      pericentrosomal polarized continuous Golgi ribbon structure, a critical feature
      for cell polarity in mammalian cells. In addition, I comment on the important
      role of the Golgi-nucleated MTs in organizing specialized MT arrays that serve
      specific functions in terminally differentiated cells. 

PMID- 25047617
TI  - Communication, the centrosome and the immunological synapse.
AB  - Recent findings on the behaviour of the centrosome at the immunological synapse
      suggest a critical role for centrosome polarization in controlling the
      communication between immune cells required to generate an effective immune
      response. The features observed at the immunological synapse show parallels to
      centrosome (basal body) polarization seen in cilia and flagella, and the cellular
      communication that is now known to occur at all of these sites. 

PMID- 25047618
TI  - Centrosomes as signalling centres.
AB  - Centrosomes-as well as the related spindle pole bodies (SPBs) of yeast-have been
      extensively studied from the perspective of their microtubule-organizing roles.
      Moreover, the biogenesis and duplication of these organelles have been the
      subject of much attention, and the importance of centrosomes and the centriole
      ciliary apparatus for human disease is well recognized. Much less developed is
      our understanding of another facet of centrosomes and SPBs, namely their possible
      role as signalling centres. Yet, many signalling components, including kinases
      and phosphatases, have been associated with centrosomes and spindle poles, giving
      rise to the hypothesis that these organelles might serve as hubs for the
      integration and coordination of signalling pathways. In this review, we discuss a
      number of selected studies that bear on this notion. We cover different processes
      (cell cycle control, development, DNA damage response) and organisms (yeast,
      invertebrates and vertebrates), but have made no attempt to be comprehensive.
      This field is still young and although the concept of centrosomes and SPBs as
      signalling centres is attractive, it remains primarily a concept-in need of
      further scrutiny. We hope that this review will stimulate thought and
      experimentation. 

PMID- 25047619
TI  - How do cilia organize signalling cascades?
AB  - Cilia and flagella are closely related centriole-nucleated protrusions of the
      cell with roles in motility and signal transduction. Two of the best-studied
      signalling pathways organized by cilia are the transduction cascade for the
      morphogen Hedgehog in vertebrates and the mating pathway that initiates gamete
      fusion in the unicellular green alga Chlamydomonas reinhardtii. What is the role
      of cilia in these signalling transduction cascades? In both Hedgehog and mating
      pathways, all signalling intermediates have been found to localize to cilia, and,
      for some signalling factors, ciliary localization is regulated by pathway
      activation. Given a concentration factor of three orders of magnitude provided by
      translocating a protein into the cilium, the compartment model proposes that
      cilia act as miniaturized reaction tubes bringing signalling factors and
      processing enzymes in close proximity. On the other hand, the scaffolding model
      views the intraflagellar transport machinery, whose primary function is to build
      cilia and flagella, as a molecular scaffold for the mating transduction cascade
      at the flagellar membrane. While these models may coexist, it is hoped that a
      precise understanding of the mechanisms that govern signalling inside cilia will
      provide a satisfying answer to the question 'how do cilia organize signalling?'.
      This review covers the evidence supporting each model of signalling and outlines
      future directions that may address which model applies in given biological
      settings. 

PMID- 25047620
TI  - When fate follows age: unequal centrosomes in asymmetric cell division.
AB  - A strong correlation between centrosome age and fate has been reported in some
      stem cells and progenitors that divide asymmetrically. In some cases, such
      stereotyped centrosome behaviour is essential to endow stemness to only one of
      the two daughters, whereas in other cases causality is still uncertain. Here, we
      present the different cell types in which correlated centrosome age and fate has
      been documented, review current knowledge on the underlying molecular mechanisms
      and discuss possible functional implications of this process.

PMID- 25047623
TI  - Historical roots of centrosome research: discovery of Boveri's microscope slides
      in Wurzburg.
AB  - Boveri's visionary monograph 'Ueber die Natur der Centrosomen' (On the nature of
      centrosomes) in 1900 was founded primarily on microscopic observations of
      cleaving eggs of sea urchins and the roundworm parasite Ascaris. As Boveri wrote
      in the introductory paragraph, his interests were less about morphological
      aspects of centrosomes, but rather aimed at an understanding of their
      physiological role during cell division. The remarkable transition from
      observations of tiny dot-like structures in fixed and sectioned material to a
      unified theory of centrosome function (which in essence still holds true today)
      cannot be fully appreciated without examining Boveri's starting material, the
      histological specimens. It was generally assumed that the microscope slides were
      lost during the bombing of the Zoological Institute in Wurzburg at the end of
      WWII. Here, I describe the discovery of a number of Boveri's original microscope
      slides with serial sections of early sea urchin and Ascaris embryos, stained by
      Heidenhain's iron haematoxylin method. Some slides bear handwritten notes and
      sketches by Boveri. Evidence is presented that the newly discovered slides are
      part of the original material used by Boveri for his seminal centrosome
      monograph.

PMID- 25047624
TI  - Successful treatment of excessive supragastric belching by combination of
      pregabalin and baclofen.

PMID- 25047621
TI  - Causes and consequences of centrosome abnormalities in cancer.
AB  - Centrosome amplification is a hallmark of cancer. However, despite significant
      progress in recent years, we are still far from understanding how centrosome
      amplification affects tumorigenesis. Boveri's hypothesis formulated more than 100
      years ago was that aneuploidy induced by centrosome amplification promoted
      tumorigenesis. Although the hypothesis remains appealing 100 years later, it is
      also clear that the role of centrosome amplification in cancer is more complex
      than initially thought. Here, we review how centrosome abnormalities are
      generated in cancer and the mechanisms cells employ to adapt to centrosome
      amplification, in particular centrosome clustering. We discuss the different
      mechanisms by which centrosome amplification could contribute to tumour
      progression and the new advances in the development of therapies that target
      cells with extra centrosomes. 

PMID- 25047622
TI  - Small organelle, big responsibility: the role of centrosomes in development and
      disease.
AB  - The centrosome, a key microtubule organizing centre, is composed of centrioles,
      embedded in a protein-rich matrix. Centrosomes control the internal spatial
      organization of somatic cells, and as such contribute to cell division, cell
      polarity and migration. Upon exiting the cell cycle, most cell types in the human
      body convert their centrioles into basal bodies, which drive the assembly of
      primary cilia, involved in sensing and signal transduction at the cell surface.
      Centrosomal genes are targeted by mutations in numerous human developmental
      disorders, ranging from diseases exclusively affecting brain development, through
      global growth failure syndromes to diverse pathologies associated with ciliary
      malfunction. Despite our much-improved understanding of centrosome function in
      cellular processes, we know remarkably little of its role in the organismal
      context, especially in mammals. In this review, we examine how centrosome
      dysfunction impacts on complex physiological processes and speculate on the
      challenges we face when applying knowledge generated from in vitro and in vivo
      model systems to human development. 

PMID- 25047625
TI  - Discrete microstructural cues for the attenuation of fibrosis following
      myocardial infarction.
AB  - Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased
      morbidity and mortality due to cardiac dysfunction. We have developed a
      therapeutic materials strategy that aims to mitigate myocardial fibrosis by
      utilizing injectable polymeric microstructures to mechanically alter the
      microenvironment. Polymeric microstructures were fabricated using
      photolithographic techniques and studied in a three-dimensional culture model of
      the fibrotic environment and by direct injection into the infarct zone of adult
      rats. Here, we show dose-dependent down-regulation of expression of genes
      associated with the mechanical fibrotic response in the presence of
      microstructures. Injection of this microstructured material into the infarct zone
      decreased levels of collagen and TGF-beta, increased elastin deposition and
      vascularization in the infarcted region, and improved functional outcomes after
      six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic
      microstructures and suggest a potential therapeutic materials approach for
      combatting pathologic fibrosis. 

PMID- 25047626
TI  - A composite hydrogel platform for the dissection of tumor cell migration at
      tissue interfaces.
AB  - Glioblastoma multiforme (GBM), the most prevalent primary brain cancer, is
      characterized by diffuse infiltration of tumor cells into brain tissue, which
      severely complicates surgical resection and contributes to tumor recurrence. The
      most rapid mode of tissue infiltration occurs along blood vessels or white matter
      tracts, which represent topological interfaces thought to serve as "tracks" that
      speed cell migration. Despite this observation, the field lacks experimental
      paradigms that capture key features of these tissue interfaces and allow
      reductionist dissection of mechanisms of this interfacial motility. To address
      this need, we developed a culture system in which tumor cells are sandwiched
      between a fibronectin-coated ventral surface representing vascular basement
      membrane and a dorsal hyaluronic acid (HA) surface representing brain parenchyma.
      We find that inclusion of the dorsal HA surface induces formation of adhesive
      complexes and significantly slows cell migration relative to a free fibronectin
      coated surface. This retardation is amplified by inclusion of integrin binding
      peptides in the dorsal layer and expression of CD44, suggesting that the dorsal
      surface slows migration through biochemically specific mechanisms rather than
      simple steric hindrance. Moreover, both the reduction in migration speed and
      assembly of dorsal adhesions depend on myosin activation and the stiffness of the
      ventral layer, implying that mechanochemical feedback directed by the ventral
      layer can influence adhesive signaling at the dorsal surface. 

PMID- 25047627
TI  - A shape-controlled tuneable microgel platform to modulate angiogenic paracrine
      responses in stem cells.
AB  - Development of cell delivery platforms have been driven based on an empirical
      cytoprotective design. While cell-matrix and cell-cell interactions that
      influence biochemical effects beyond survival has been limited and overshadowed
      in an effort to incrementally improve biomimicking properties of the tissue
      engineered constructs. Here we demonstrate fabrication of a shape controlled 3D
      type-I collagen-based microgel platform that can be tuned to modulate angiogenic
      paracrine- 'angiocrine' responses of human mesenchymal stem cells (hMSCs).
      Furthermore, these microgels were characterized as a 3D cell culture tool to
      assess optimal biological response as a function of cell-matrix and cell-cell
      interactions. Finally, optimised hMSC embedded microgels were shown to induce
      vascular repair and functional improvement in vivo in a mouse model of hind-limb
      ischemia. The approach described here in designing a tuneable cell delivery
      platform using naturally occurring extracellular matrix molecules highlights the
      need for highly customised matrices with an array of self-assembling proteins
      that dictate specific cell function resembling the native tissue of interest for
      repair. 

PMID- 25047628
TI  - Influence of the stiffness of three-dimensional alginate/collagen-I
      interpenetrating networks on fibroblast biology.
AB  - Wound dressing biomaterials are increasingly being designed to incorporate
      bioactive molecules to promote healing, but the impact of matrix mechanical
      properties on the biology of resident cells orchestrating skin repair and
      regeneration remains to be fully understood. This study investigated whether
      tuning the stiffness of a model wound dressing biomaterial could control the
      behavior of dermal fibroblasts. Fully interpenetrating networks (IPNs) of
      collagen-I and alginate were fabricated to enable gel stiffness to be tuned
      independently of gel architecture, polymer concentration or adhesion ligand
      density. Three-dimensional cultures of dermal fibroblasts encapsulated within
      matrices of different stiffness were shown to promote dramatically different cell
      morphologies, and enhanced stiffness resulted in upregulation of key-mediators of
      inflammation such as IL-10 and COX-2. These findings suggest that simply
      modulating the matrix mechanical properties of a given wound dressing biomaterial
      deposited at the wound site could regulate the progression of wound healing. 

PMID- 25047629
TI  - Dual growth factor delivery from bilayered, biodegradable hydrogel composites for
      spatially-guided osteochondral tissue repair.
AB  - The present work investigated the use of biodegradable hydrogel composite
      scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to
      deliver growth factors for the repair of osteochondral tissue in a rabbit model.
      In particular, bilayered OPF composites were used to mimic the structural layers
      of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone
      morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and
      embedded within the OPF hydrogel matrix in a spatially controlled manner. Three
      different scaffold formulations were implanted in a medial femoral condyle
      osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral
      layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity
      and quality of osteochondral repair was evaluated at 6 and 12 weeks with
      histological scoring and micro-computed tomography (micro-CT). While histological
      scoring results at 6 weeks showed no differences between experimental groups,
      micro-CT analysis revealed that the delivery of BMP-2 alone increased the number
      of bony trabecular islets formed, an indication of early bone formation, over
      that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences
      were detected between the three groups for cartilage repair. However, the dual
      delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair,
      greater bone growth at the defect margins, and lower bone specific surface than
      the single delivery of IGF-1. These results suggest that the delivery of BMP-2
      enhances subchondral bone formation and that, while the dual delivery of IGF-1
      and BMP-2 in separate layers does not improve cartilage repair under the
      conditions studied, they may synergistically enhance the degree of subchondral
      bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential
      as spatially-guided, multiple growth factor release vehicles for osteochondral
      tissue repair. 

PMID- 25047630
TI  - Engineering a morphogenetically active hydrogel for bioprinting of bioartificial
      tissue derived from human osteoblast-like SaOS-2 cells.
AB  - Sodium alginate hydrogel, stabilized with gelatin, is a suitable, biologically
      inert matrix that can be used for encapsulating and 3D bioprinting of bone
      related SaOS-2 cells. However, the cells, embedded in this matrix, remain in a
      non-proliferating state. Here we show that addition of an overlay onto the
      bioprinted alginate/gelatine/SaOS-2 cell scaffold, consisting of agarose and the
      calcium salt of polyphosphate [polyP.Ca(2+)-complex], resulted in a marked
      increase in cell proliferation. In the presence of 100 MUm polyP.Ca(2+)-complex,
      the cells proliferate with a generation time of approximately 47-55 h. In
      addition, the hardness of the alginate/gelatin hydrogel substantially increases
      in the presence of the polymer. The reduced Young's modulus for the
      alginate/gelatin hydrogel is approximately 13-14 kPa, and this value drops to
      approximately 0.5 kPa after incubation of the cell containing scaffolds for 5 d.
      In the presence of 100 MUm polyP.Ca(2+)-complex, the reduced Young's modulus
      increases to about 22 kPa. The hardness of the polyP.Ca(2+)-complex containing
      hydrogel remains essentially constant if cells are absent in the matrix, but it
      drops to 3.2 kPa after a 5 d incubation period in the presence of SaOS-2 cells,
      indicating that polyP.Ca(2+)-complex becomes metabolized, degraded, by the cells.
      The alginate/gelatine-agarose system with polyP.Ca(2+)-complex cause a
      significant increase in the mineralization of the cells. SEM analyses revealed
      that the morphology of the mineral nodules formed on the surface of the cells
      embedded in the alginate/gelatin hydrogel do not significantly differ from the
      nodules on cells growing in monolayer cultures. The newly developed technique,
      using cells encapsulated into an alginate/gelatin hydrogel and a secondary layer
      containing the morphogenetically active, growth promoting polymer polyP.Ca(2+)
      complex opens new possibilities for the application of 3D bioprinting in bone
      tissue engineering. 

PMID- 25047631
TI  - Real-time manipulation with magnetically tunable structures.
AB  - Magnetically tunable micropillar arrays with uniform, continuous and extreme tilt
      angles for real-time manipulation are reported. We experimentally show uniform
      tilt angles ranging from 0 degrees  to 57 degrees , and develop a model to
      accurately capture the behavior. Furthermore, we demonstrate that the flexible
      uniform responsive microstructures (MUFUR) can dynamically manipulate liquid
      spreading directionality, control fluid drag, and tune optical transmittance over
      a large range. 

PMID- 25047632
TI  - Liposarcoma: a soft tissue tumor with many presentations.
AB  - Liposarcoma is an uncommon connective tissue tumor arising from lipoblast cells.
      The lesion is located in body soft parts and rarely arises from the bones. The
      tumors are variable in presentation ranging from benign well-differentiated
      tumors to myxoid and round cell-dedifferentiated and pleomorphic forms which can
      present with metastases. The lesions are most often treated by surgical
      resection. Chemotherapy and radiation may be added to the treatment of the more
      malignant variants with some success. 

PMID- 25047633
TI  - Sudden death of a 14-year-old girl with lymphangiomatosis.
AB  - A 14-year-old girl presented with progressively worsening intermittent orthopnea.
      Imaging studies showed cardiomegaly, extensive pericardial effusion, and a
      mediastinal tumor. By pericardial drainage, approximately 8,000-mL fluid was
      collected over 10 days. Left thoracoscopic pericardial fenestration and
      mediastinal tumor biopsy were performed, revealing lymphangiomatosis. Chylous
      pleural effusion developed post-surgery. Although control was attempted, her
      condition worsened. Eight months later, she died of sudden cardiopulmonary
      arrest. Autopsy revealed systemic spread of the primary lesion from the
      hyperplastic lymph ducts to the parietal pleura and mediastinum confirming
      systemic lymphangiomatosis.

PMID- 25047635
TI  - Differential effects of lipid fractions from silver carp brain on human cervical
      carcinoma cells in vitro.
AB  - Previous research has revealed that n3 polyunsaturated fatty acids (PUFAs)
      exhibit anticancer activities. Lipids from a fish brain contain substantial n3
      PUFAs. However, no research has been conducted on the action and mechanism of
      their potent anticancer activities. In this study, total lipids (TLs) from silver
      carp brain were isolated into polar lipids (PLs) and neutral lipids (NLs), and
      the anticancer potential of the lipid fractions (LFs) was investigated using the
      human cervical carcinoma HeLa cell line. LFs effectively inhibited the cell
      proliferation of HeLa cells in a time- and dose-dependent manner by cell cycle
      arrest at the S stage and by inducing apoptosis. Further analyses indicated that
      the loss of mitochondrial membrane potential could be one of mechanisms of
      apoptosis induced by LFs. Among the TLs, PLs have proven to be more effective in
      inducing cervical carcinoma cell death than NLs. This work will play a role in
      promoting lipids from silver carp brain as a potential preventive and therapeutic
      agent against human cervical carcinoma. 

PMID- 25047634
TI  - Association of antibody responses to the conserved Plasmodium falciparum
      merozoite surface protein 5 with protection against clinical malaria.
AB  - BACKGROUND: Plasmodium falciparum merozoite surface protein 5 (PfMSP5) is an
      attractive blood stage vaccine candidate because it is both exposed to the immune
      system and well conserved. To evaluate its interest, we investigated the
      association of anti-PfMSP5 IgG levels, in the context of responses to two other
      conserved Ags PfMSP1p19 and R23, with protection from clinical episodes of
      malaria in cross-sectional prospective studies in two different transmission
      settings. METHODS: Ndiop (mesoendemic) and Dielmo (holoendemic) are two
      Senegalese villages participating in an on-going long-term observational study of
      natural immunity to malaria. Blood samples were taken before the transmission
      season (Ndiop) or before peak transmission (Dielmo) and active clinical
      surveillance was carried out during the ensuing 5.5-month follow-up. IgG
      responses to recombinant PfMSP5, PfMSP1p19 and R23 were quantified by ELISA in
      samples from surveys carried out in Dielmo (186 subjects) and Ndiop (221
      subjects) in 2002, and Ndiop in 2000 (204 subjects). In addition, 236 sera from
      the Dielmo and Ndiop-2002 surveys were analyzed for relationships between the
      magnitude of anti-PfMSP5 response and neutrophil antibody dependent respiratory
      burst (ADRB) activity. RESULTS: Anti-PfMSP5 antibodies predominantly IgG1 were
      detected in 60-74% of villagers, with generally higher levels in older age
      groups. PfMSP5 IgG responses were relatively stable for Ndiop subjects sampled
      both in 2000 and 2002. ADRB activity correlated with age and anti-PfMSP5 IgG
      levels. Importantly, PfMSP5 antibody levels were significantly associated with
      reduced incidence of clinical malaria in all three cohorts. Inclusion of IgG to
      PfMSP1p19 in the poisson regression model did not substantially modify results.
      CONCLUSION: These results indicate that MSP5 is recognized by naturally acquired
      Ab. The large seroprevalence and association with protection against clinical
      malaria in two settings with differing transmission conditions and stability over
      time demonstrated in Ndiop argue for further evaluation of baculovirus PfMSP5 as
      a vaccine candidate.

PMID- 25047637
TI  - Subclinical deformities of the hip are significant predictors of radiographic
      osteoarthritis and joint replacement in women. A 20 year longitudinal cohort
      study.
AB  - OBJECTIVE: Femoroacetabular Impingement (FAI) and Acetabular Dysplasia are common
      deformities, which have been implicated as a major cause of hip osteoarthritis
      (OA). We examined whether these subtle deformities of the hip are associated with
      the development of radiographic OA and total hip replacement (THR) in women.
      DESIGN: A population-based, longitudinal cohort of 1003 women underwent pelvis
      radiographs at years 2 and 20. Alpha Angle, Triangular Index Height, Lateral
      Centre Edge (LCE) angle and Extrusion Index were measured. An alpha angle of
      greater than 65 degrees  was defined as Cam-type FAI. Radiographic OA and the
      presence of a THR were then determined at 20 years. RESULTS: Cam-type FAI was
      significantly associated with the development of radiographic OA. Each degree
      increase in alpha angle above 65 degrees  was associated with an increase in risk
      of 5% (Odds Ratio (OR) 1.05 [95% confidence interval (CI) 1.01-1.09]) for
      radiographic OA and 4% (OR 1.04 [95% CI 1.00-1.08]) for THR. For Acetabular
      Dysplasia, each degree reduction in LCE angle below 28 degrees  was associated
      with an increase in risk of 13.0% (OR 0.87 [95% CI 0.78-0.96]) for radiographic
      OA and 18% (OR 0.82 [95% CI 0.75-0.89]) for THR. CONCLUSIONS: This study
      demonstrates that Cam-type FAI and mild Acetabular Dysplasia are predictive of
      subsequent OA and THR in a large female population cohort. These are independent
      of age, BMI and joint space and significantly improve current predictive models
      of hip OA development.

PMID- 25047638
TI  - The effect of low dose rate on metabolomic response to radiation in mice.
AB  - Metabolomics has been shown to have utility in assessing responses to exposure by
      ionizing radiation (IR) in easily accessible biofluids such as urine. Most
      studies to date from our laboratory and others have employed gamma-irradiation at
      relatively high dose rates (HDR), but many environmental exposure scenarios will
      probably be at relatively low dose rates (LDR). There are well-documented
      differences in the biologic responses to LDR compared to HDR, so an important
      question is to assess LDR effects at the metabolomics level. Our study took
      advantage of a modern mass spectrometry approach in exploring the effects of dose
      rate on the urinary excretion levels of metabolites 2 days after IR in mice. A
      wide variety of statistical tools were employed to further focus on metabolites,
      which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from
      those of HDR. From a total of 709 detected spectral features, more than 100 were
      determined to be statistically significant when comparing urine from mice
      irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post
      exposure. The results of this study show that LDR and HDR exposures perturb many
      of the same pathways such as TCA cycle and fatty acid metabolism, which also have
      been implicated in our previous IR studies. However, it is important to note that
      dose rate did affect the levels of particular metabolites. Differences in urinary
      excretion levels of such metabolites could potentially be used to assess an
      individual's exposure in a radiobiological event and thus would have utility for
      both triage and injury assessment.

PMID- 25047639
TI  - The neutral self-assembling peptide hydrogel SPG-178 as a topical hemostatic
      agent.
AB  - Conventional self-assembling peptide hydrogels are effective as topical
      hemostatic agents. However, there is a possibility to harm living tissues due to
      their low pH. The aim of the present study was to demonstrate the efficacy of SPG
      178, a neutral self-assembling peptide hydrogel, as a topical hemostatic agent.
      First, we measured the bleeding duration of incisions made on rat livers after
      application of SPG-178 (1.0% w/v), SPG-178 (1.5% w/v), RADA16 (1.0% w/v), and
      saline (n = 12/group). Second, we observed the bleeding surfaces by transmission
      electron microscopy immediately after hemostasis. Third, we measured the elastic
      and viscous responses (G' and G", respectively) of the hydrogels using a
      rheometer. Our results showed that bleeding duration was significantly shorter in
      the SPG-178 group than in the RADA16 group and that there were no significant
      differences in transmission electron microscopy findings between the groups. The
      greater the G' value of a hydrogel, the shorter was the bleeding duration. We
      concluded that SPG-178 is more effective and has several advantages: it is non
      biological, transparent, nonadherent, and neutral and can be sterilized by
      autoclaving. 

PMID- 25047640
TI  - NMDA receptors on zebrafish Mauthner cells require CaMKII-alpha for normal
      development.
AB  - Calcium/calmodulin dependent protein kinase 2 (CaMKII) is a multifunctional
      protein that is highly enriched in the synapse. It plays important roles in
      neuronal functions such as synaptic plasticity, synaptogenesis, and neural
      development. Gene duplication in zebrafish has resulted in the occurrence of
      seven CaMKII genes (camk2a, camk2b1, camk2b2, camk2g1, camk2g2, camk2d1, and
      camk2d2) that are developmentally expressed. In this study, we used single cell,
      real-time quantitative PCR to investigate the expression of CaMKII genes in
      individual Mauthner cells (M-cells) of 2 days post fertilization (dpf) zebrafish
      embryos. We found that out of seven different CaMKII genes, only the mRNA for
      CaMKII-alpha was expressed in the M-cell at detectable levels, while all other
      isoforms were undetectable. Morpholino knockdown of CaMKII-alpha had no
      significant effect on AMPA synaptic currents (mEPSCs) but decreased the amplitude
      of NMDA mEPSCs. NMDA events exhibited a biexponential decay with taufast ~ 30 ms
      and tauslow ~ 300 ms. Knockdown of CaMKII-alpha specifically reduced the
      amplitude of the slow component of the NMDA-mediated currents (mEPSCs), without
      affecting the fast component, the frequency, or the kinetics of the mEPSCs.
      Immunolabelling of the M-cell showed increased dendritic arborizations in the
      morphants compared with controls, and knockdown of CaMKII-alpha altered locomotor
      behaviors of touch responses. These results suggest that CaMKII-alpha is present
      in embryonic M-cells and that it plays a role in the normal development of
      excitatory synapses. Our findings pave the way for determining the function of
      specific CaMKII isoforms during the early stages of M-cell development.

PMID- 25047641
TI  - The glucocorticoid receptor 1A3 promoter correlates with high sensitivity to
      glucocorticoid-induced apoptosis in human lymphocytes.
AB  - Glucocorticoids (GCs) are powerful inhibitors of inflammation and immunity.
      Although glucocorticoid-induced cell death (GICD) is an important part of GCs
      actions, the cell types and molecular mechanisms involved are not well
      understood. Untranslated exon 1A3 of the human glucocorticoid receptor (GR) gene
      is a major determinant of GICD in GICD-sensitive human cancer cell lines,
      operating to dynamically upregulate GR levels in response to GCs. We measured the
      GICD sensitivity of freshly isolated peripheral blood mononuclear cells and
      thymocytes to dexamethasone in vitro, relating this to GR exon 1A3 expression. A
      clear GICD sensitivity hierarchy was detected: B cells>thymocytes/natural killer
      (NK) cells>peripheral T cells. Within thymocyte populations, GICD sensitivity
      decreased with maturation. Interestingly, NK cell subsets were differentially
      sensitive to GICD, with CD16(+)CD56(int) (cytotoxic) NK cells being highly
      resistant to GICD, whereas CD16(-)CD56(hi) (cytokine producing) NK cells were
      highly sensitive (similar to B cells). B-cell GICD was rescued by co-culture with
      interleukin-4. Strikingly, although no significant increases in GR protein were
      observed during 48 h of culture of GICD-sensitive and -resistant cells alike, GR
      1A3 expression was increased over pre-culture levels in a manner directly
      proportional to the GICD sensitivity of each cell type. Accordingly, this is the
      first evidence that the GR exon 1A3 promoter is differentially regulated during
      thymic development and maturation of human T cells. Furthermore, human peripheral
      blood B cells are exquisitely GICD-sensitive in vitro, giving new insight into
      how GCs may downregulate immunity. Collectively, these data show that GR 1A3
      expression is tied with GICD sensitivity in human lymphocytes, underscoring the
      potential for GR 1A3 expression to be used as a biomarker for sensitivity to
      GICD.

PMID- 25047642
TI  - Human memory B cells isolated from blood and tonsils are functionally
      distinctive.
AB  - Human B-cell studies in vitro have routinely used B lymphocytes purified from
      spleen, blood or tonsils irrespective of potential differences in their
      immunological traits. In this study, we compared the functional responses of
      total (CD19(+)) and memory B cells (Bmem; CD19(+)/CD27(+)) isolated from blood
      and tonsils to different stimuli. Peripheral B cells showed enhanced survival and
      proliferation compared with their tonsillar equivalents when stimulated for 10
      days. Stimulated B cells from both tissues secreted significantly greater amounts
      of cytokines than unstimulated controls demonstrating their functional
      responsiveness. Analysis of CD27 expression over time indicated that the
      conditions that promoted survival and proliferation of peripheral Bmem, caused
      massive tonsillar Bmem death. Purified tonsillar Bmem failed to expand but
      rapidly differentiated in antibody secreting cells and subsequently underwent
      apoptosis. In contrast, circulating Bmem showed delayed activation and
      differentiation, but exhibited a longer lifespan and active proliferation. In
      addition, short-term stimulation of tonsillar Bmem resulted in the production of
      more immunoglobulin G (IgG) than their peripheral counterparts. At later time
      points, however, IgG production from the different B cells was reversed. Our
      findings imply that the tissue located and peripheral Bmem have distinct
      behaviors, indicating organ dependent functional responses that should not be
      generalizable to all Bmem. This work provides a greater understanding of how Bmem
      location is coupled to specialized roles of B lymphocytes. 

PMID- 25047643
TI  - GILZ: a new link between the hypothalamic pituitary adrenal axis and rheumatoid
      arthritis?
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is an important regulator of the
      stress response. In healthy individuals, the HPA axis maintains an equilibrium,
      ensuring that endogenous glucocorticoid (GC) levels remain within the normal
      range. However, hypofunction of the HPA axis may have a role in the development
      of inflammatory diseases, such as rheumatoid arthritis (RA). Glucocorticoid
      induced leucine zipper (GILZ) is an anti-inflammatory protein, the expression of
      which is upregulated by GC. Although GILZ mediates the anti-inflammatory effects
      of GC, it may not be associated with the adverse effects that are frequently
      caused by exogenous GC administration. This has raised interest in GILZ
      potentiation as a therapeutic approach in diseases such as RA, which may mimic
      the anti-inflammatory effects of GC without causing harmful side effects. This
      review will outline the involvement of the HPA axis in RA, as a prelude to
      highlighting emerging evidence regarding the role of GILZ in inflammation control
      and RA. 

PMID- 25047644
TI  - Members of the novel UBASH3/STS/TULA family of cellular regulators suppress T
      cell-driven inflammatory responses in vivo.
AB  - The UBASH3/STS/TULA family consists of two members sharing substantial homology
      and a similar multi-domain architecture, which includes a C-terminal histidine
      phosphatase domain capable of dephosphorylating phosphotyrosine-containing
      substrates. TULA-family proteins act as downregulators of receptor-induced
      activation in several cell types, including T cells and platelets. Deletion of
      both family members in mice has been shown to result in hyperresponsiveness of T
      cells to T-cell receptor (TCR)/CD3 complex engagement, but little is known about
      the biological consequences of double knockout (dKO) and especially of either
      single KO (sKO). We elucidated the biological consequences of the lack of TULA
      family proteins in dKO and TULA and TULA-2 sKO animals. In order to do so, we
      examined immune responses in Trinitrobenzene sulfonic acid (TNBS)-induced
      colitis, a mouse model of human inflammatory bowel disease, which is
      characterized by the involvement of multiple cell types, of which T cells have a
      crucial role, in the development of a pathological inflammatory condition. Our
      data indicate that TNBS treatment upregulates T-cell responses in all KO mice
      studied to a significantly higher degree than in wild-type mice. Although the
      lack of either TULA-family member exacerbates inflammation and T-cell responses
      in a specific fashion, the lack of both TULA and TULA-2 in dKO exerts a higher
      effect than the lack of a single family member in TULA and TULA-2 sKO. Analysis
      of T-cell responses and TCR-mediated signaling argues that the proteins
      investigated affect T-cell signaling by regulating phosphorylation of Zap-70, a
      key protein tyrosine kinase. 

PMID- 25047646
TI  - Workplace violence against clinicians in Cypriot emergency departments: a
      national questionnaire survey.
AB  - AIMS AND OBJECTIVES: To identify perceived prevalence, characteristics,
      precipitating factors and suggestions for improving workplace violence in all
      nine public emergency departments in the Cyprus Republic. BACKGROUND: Workplace
      violence is a common phenomenon in emergency departments, but little is known
      about this phenomenon in Cyprus. DESIGN: A retrospective cross-sectional survey.
      METHODS: Two hundred and twenty of 365 emergency nurses (85.7%) and doctors
      (14.3%) participated in this study, of which 62% were female. Data were collected
      via a Greek language version of the Violent Incident Form. Additional questions
      examined perceived frequencies, encouragement for reporting, satisfaction with
      actions taken and suggestions for improvement. Descriptive analysis, chi-square
      tests and multiple logistic regression analyses were used to describe and
      associate characteristics with workplace prevalence. RESULTS: During the previous
      12 months, the vast majority of nurses and doctors (76.2%) were exposed to verbal
      abuse (88.8%), mainly by relatives or friends of the patient (59.1%). Relatively
      inexperienced clinicians were at greater risk. Waiting time was identified as the
      most significant organisational factor. Alcohol intoxication, substance abuse and
      mental illness were individual factors for workplace violence. Severe
      underreporting (72.2%) and a belief that workplace violence is part of the work
      (74.1%) were also identified. Workplace violence was highly correlated with
      several factors, including a lack of encouragement for reporting, a feeling in
      advance that a violent incident was about to happen and having to handle the
      incident personally. Suggestions for improvement included more security measures
      (26.7%) and public education about the proper use of emergency services (15.2%).
      CONCLUSION: Verbal abuse is common in Cypriot emergency departments, but
      clinicians are increasingly worried about physical assaults. RELEVANCE TO
      CLINICAL PRACTICE: Training, security policies, encouragement of reporting and
      support for staff after a violent incident are needed. Future research should try
      to include the perpetrator's viewpoint.

PMID- 25047645
TI  - Reduced GABAergic inhibition in the basolateral amygdala and the development of
      anxiety-like behaviors after mild traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major public health concern affecting a large
      number of athletes and military personnel. Individuals suffering from a TBI risk
      developing anxiety disorders, yet the pathophysiological alterations that result
      in the development of anxiety disorders have not yet been identified. One region
      often damaged by a TBI is the basolateral amygdala (BLA); hyperactivity within
      the BLA is associated with increased expression of anxiety and fear, yet the
      functional alterations that lead to BLA hyperexcitability after TBI have not been
      identified. We assessed the functional alterations in inhibitory synaptic
      transmission in the BLA and one mechanism that modulates excitatory synaptic
      transmission, the alpha7 containing nicotinic acetylcholine receptor (alpha7
      nAChR), after mTBI, to shed light on the mechanisms that contribute to increased
      anxiety-like behaviors. Seven and 30 days after a mild controlled cortical impact
      (CCI) injury, animals displayed significantly greater anxiety-like behavior. This
      was associated with a significant loss of GABAergic interneurons and significant
      reductions in the frequency and amplitude of spontaneous and miniature GABAA
      receptor mediated inhibitory postsynaptic currents (IPSCs). Decreases in the
      mIPSC amplitude were associated with reduced surface expression of alpha1, beta2,
      and gamma2 GABAA receptor subunits. However, significant increases in the surface
      expression and current mediated by alpha7-nAChR, were observed, signifying
      increases in the excitability of principal neurons within the BLA. These results
      suggest that mTBI causes not only a significant reduction in inhibition in the
      BLA, but also an increase in neuronal excitability, which may contribute to
      hyperexcitability and the development of anxiety disorders. 

PMID- 25047647
TI  - Nitrogen deprivation induces lipid droplet accumulation and alters fatty acid
      metabolism in symbiotic dinoflagellates isolated from Aiptasia pulchella.
AB  - The stability of cnidarian-dinoflagellate (genus Symbiodinium spp.) endosymbioses
      depends on the regulation of nutrient transport between Symbiodinium populations
      and their hosts. Previously, we successfully induced the production of lipid
      droplets in the free-living cultured Symbiodinium (clade B) under the nitrogen
      deprivation condition for 5 days. Therefore, the present study aimed at
      understanding the disruption of the endosymbiotic relationship between the
      cnidarians and dinoflagellates by nitrogen deprivation using Aiptasia pulchella
      as an example. Transmission electron micrographs revealed the formation of lipid
      droplets induced by nitrogen deprivation, and the lipid analyses further showed
      that polyunsaturated fatty acids were drastically enriched in Symbiodinium after
      30 days of nitrogen deprivation, although these were unaffected after 5 days of
      nitrogen starvation. The present study also suggested that the host provided
      nitrogen to the symbiotic cells during short-term environmental stress. However,
      the relationship started to deteriorate after 30 days. These findings provide a
      more detailed understanding of the mechanisms of the symbiotic relationship
      between the symbiotic dinoflagellates in terms of the nitrogen source, which
      might provide more information for the explanation of the regulatory mechanism
      underlying endosymbiotic associations. 

PMID- 25047648
TI  - Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in
      children with a high genetic risk of type 1 diabetes: the MIDIA study.
AB  - AIMS/HYPOTHESIS: Only a few longitudinal molecular studies of enterovirus and
      islet autoimmunity have been reported, and positive results seem to be limited to
      Finland. We aimed to investigate an association between enterovirus RNA in blood
      and islet autoimmunity in the MIDIA study from Norway, a country which largely
      shares environmental and economic features with Finland. METHODS: We analysed
      serial blood samples collected at ages 3, 6, and 9 months and then annually from
      45 children who developed confirmed positivity for at least two autoantibodies
      (against insulin, GAD65 and IA-2) and 92 matched controls, all from a cohort of
      children with a single high-risk HLA-DQ-DR genotype. Enterovirus was tested in
      RNA extracted from frozen blood cell pellets, using real-time RT-PCR with
      stringent performance control. RESULTS: Out of 807 blood samples, 72 (8.9%) were
      positive for enterovirus. There was no association between enterovirus RNA and
      islet autoimmunity in samples obtained strictly before (7.6% cases, 10.0%
      controls, OR 0.75 [95% CI 0.36, 1.57]), or strictly after the first detection of
      islet autoantibodies (10.5% case, 5.8% controls, OR 2.00 [95% CI 0.64, 6.27]).
      However, there was a tendency towards a higher frequency of enterovirus detection
      in the first islet autoantibody-positive sample (15.8%) compared with the
      corresponding time point in matched controls (3.2%, OR 8.7 [95% CI 0.97, 77]).
      Neither of these results was changed by adjusting for potential confounders,
      restricting to various time intervals or employing various definitions of
      enterovirus positivity. CONCLUSIONS/INTERPRETATION: Positivity for enterovirus
      RNA in blood did not predict the later induction of islet autoantibodies, but
      enterovirus tended to be detected more often at the islet autoantibody
      seroconversion stage.

PMID- 25047649
TI  - Estimates of insulin sensitivity from the intravenous-glucose-modified-clamp test
      depend on suppression of lipolysis in type 2 diabetes: a randomised controlled
      trial.
AB  - AIMS/HYPOTHESIS: The combined IVGTT-hyperinsulinaemic-euglycaemic clamp (Botnia
      clamp) allows the assessment of insulin secretion and sensitivity in one
      experiment. It remains unclear whether this clamp yields results comparable with
      those of the standard hyperinsulinaemic-euglycaemic clamp (SHEC) in diabetes
      patients. We hypothesised that the IVGTT induces responses affecting insulin
      sensitivity assessment. METHODS: Of 22 randomised diet- or metformin-treated
      patients with well-controlled type 2 diabetes, 19 randomly underwent a Botnia
      clamp and an SHEC, spaced by 2 weeks, in one clinical research centre in a
      crossover study. The main outcomes were whole-body and hepatic insulin
      sensitivity as measured by the clamp and [6,6-(2)H2]glucose. Substrate
      utilisation was assessed from indirect calorimetry and beta cell function from
      insulin dynamics during IVGTT. RESULTS: The values of whole-body insulin
      sensitivity obtained from Botnia clamp and SHEC were correlated (r = 0.87, p <
      0.001), but also revealed intra-individual variations. Hepatic insulin
      sensitivity did not differ between experiments during the clamp, but differed
      after IVGTT. The contribution of glucose oxidation to glucose disposal increased
      by 2.2 +/- 0.3 and 1.2 +/- 0.4 mg kg fat-free mass (FFM)(-1) min(-1) (Botnia and
      SHEC, p < 0.05), whereas lipid oxidation decreased by 0.8 +/- 0.1 and 0.4 +/- 0.1
      mg kg FFM(-1) min(-1) (p < 0.05) from baseline. Differences in NEFA (r = -0.60, p
      < 0.01), but not C-peptide (r = -0.16, p = 0.52) or hepatic insulin sensitivity
      between IVGTT and placebo before the clamps correlated with individual variations
      of insulin sensitivity. CONCLUSIONS/INTERPRETATION: The Botnia clamp provides
      similar estimates of insulin sensitivity as SHEC in patients with type 2
      diabetes, but changes in NEFA during IVGTT may affect insulin sensitivity and
      thereby the discrimination between insulin-sensitive and insulin-resistant
      individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT01397279 FUNDING: The
      study was funded by the Ministry of Science and Research of the State of North
      Rhine-Westphalia and the German Federal Ministry of Health, and supported in part
      by grants from the Federal Ministry for Research to the Centers for Diabetes
      Research, Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases
      and the Schmutzler-Stiftung.

PMID- 25047651
TI  - WS2 nanosheet as a new photosensitizer carrier for combined photodynamic and
      photothermal therapy of cancer cells.
AB  - We have developed a simple and efficient strategy to fabricate WS2 nanosheets
      with low toxicity and good water solubility via a liquid exfoliation method by
      using H2SO4 intercalation and ultrasonication. The as-prepared WS2 nanosheets
      were employed not only as an NIR absorbing agent for photothermal therapy (PTT)
      but also as a photosensitizer (PS) carrier for photodynamic therapy (PDT) due to
      their sheet like structure that offers large surface area to load PS molecules.
      Moreover, singlet-oxygen generation of the PSs-WS2 complex could be finely
      controlled by NIR irradiation that could manipulate the PSs release behavior from
      WS2 nanosheets. The synergistic anti-tumor effect of WS2 nanosheets mediated PDT
      PTT was also evaluated carefully and the results clearly showed that the efficacy
      of combined PDT-PTT treatment of cancer cells is significantly higher than those
      of PDT-only and PTT-only treatment, indicating enhanced efficiency of the
      combined therapeutic system. In addition, the WS2 could be used as a computed
      tomography (CT) contrast agent for bio-imaging since W atoms have strong X-ray
      attenuation ability, making them a multifunctional theranostic platform for
      simultaneous imaging-guided diagnosis and therapy. 

PMID- 25047650
TI  - Gene discovery through transcriptome sequencing for the invasive mussel
      Limnoperna fortunei.
AB  - The success of the Asian bivalve Limnoperna fortunei as an invader in South
      America is related to its high acclimation capability. It can inhabit waters with
      a wide range of temperatures and salinity and handle long-term periods of air
      exposure. We describe the transcriptome of L. fortunei aiming to give a first
      insight into the phenotypic plasticity that allows non-native taxa to become
      established and widespread. We sequenced 95,219 reads from five main tissues of
      the mussel L. fortunei using Roche's 454 and assembled them to form a set of
      84,063 unigenes (contigs and singletons) representing partial or complete gene
      sequences. We annotated 24,816 unigenes using a BLAST sequence similarity search
      against a NCBI nr database. Unigenes were divided into 20 eggNOG functional
      categories and 292 KEGG metabolic pathways. From the total unigenes, 1,351
      represented putative full-length genes of which 73.2% were functionally
      annotated. We described the first partial and complete gene sequences in order to
      start understanding bivalve invasiveness. An expansion of the hsp70 gene family,
      seen also in other bivalves, is present in L. fortunei and could be involved in
      its adaptation to extreme environments, e.g. during intertidal periods. The
      presence of toll-like receptors gives a first insight into an immune system that
      could be more complex than previously assumed and may be involved in the
      prevention of disease and extinction when population densities are high. Finally,
      the apparent lack of special adaptations to extremely low O2 levels is a target
      worth pursuing for the development of a molecular control approach. 

PMID- 25047652
TI  - The prognostic value of electrodiagnostic testing in patients with sciatica
      receiving physical therapy.
AB  - PURPOSE: To investigate the prognostic value of electrodiagnostic testing in
      patients with sciatica receiving physical therapy. METHODS: Electrodiagnostic
      testing was performed on 38 patients with sciatica participating in a randomized
      trial comparing different physical therapy interventions. Patients were grouped
      and analyzed according to the presence or absence of radiculopathy based on
      electrodiagnostic testing. Longitudinal data analysis was conducted using
      multilevel growth modeling with ten waves of data collected from baseline through
      the treatment and post-treatment periods up to 6 months. The primary outcome
      measure was changes in low back pain-related disability assessed using the Roland
      and Morris disability questionnaire (RMDQ). RESULTS: Patients with radiculopathy
      (n = 19) had statistically significant and clinically meaningful improvements in
      RMDQ scores at every post-treatment follow-up occasion regardless of treatment
      received. The final multilevel growth model revealed improvements in RMDQ scores
      in patients with radiculopathy at the 6-week (-8.1, 95 % CI -12.6 to -2.6; P =
      0.006) and 6-month (-4.1, 95 % CI -7.4 to -0.7; P = 0.020) follow-up occasions
      compared to patients without radiculopathy. Treatment group was not a significant
      predictive factor at any follow-up occasion. An interaction between
      electrodiagnostic status and time revealed faster weekly improvements in RMDQ
      scores in patients with radiculopathy at the 6-week (-0.72, 95 % CI -1.4 to 
      0.04; P = 0.040) through the 16-week (-0.30, 95 % CI, -0.57 to -0.04; P = 0.028)
      follow-up occasions compared to patients without radiculopathy. CONCLUSIONS: The
      presence of lumbosacral radiculopathy identified with electrodiagnostic testing
      is a favorable prognostic factor for recovery in low back pain-related disability
      regardless of physical therapy treatment received.

PMID- 25047653
TI  - A multicenter study on accuracy and complications of freehand placement of
      cervical pedicle screws under lateral fluoroscopy in different pathological
      conditions: CT-based evaluation of more than 1,000 screws.
AB  - PURPOSE: To conduct a retrospective multicenter study to investigate the accuracy
      of pedicle screw (PS) placement in the cervical spine by freehand technique and
      the related complications in various pathological conditions including trauma,
      rheumatoid arthritis, degenerative conditions and others. METHODS: 283 patients
      with 1,065 PSs in the cervical spine who were treated at eight spine centers and
      finished postoperative CT scan were enrolled. The numbers of placed PSs were 608
      for trauma, 180 for rheumatoid arthritis (RA), 199 for spondylosis, and 78 for
      others. Malposition grades on CT image in the axial plane were defined as grade 0
      (G-0) correct placement, grade 1 (G-1): malposition by less than half screw
      diameter, grade 2 (G-2): malposition by more than half screw diameter. The
      direction of malposition was classified into four categories: medial, lateral,
      superior and inferior. RESULTS: Overall malposition rate was 14.8 % (9.6 % in G-1
      and 5.3 % in G-2). The highest malposition rate was 26.7 % for RA, followed by
      16.6 % for spondylosis, and 11.2 % for trauma. The malposition rate for RA was
      significantly higher than those for other pathologies. 79.7 % of the
      malpositioned screws were placed laterally. Though intraoperative vertebral
      artery injury was observed in two patients with RA, there were no serious
      complications during a minimal 2-year follow-up. CONCLUSIONS: Malposition rate of
      PS placement in the cervical spine by freehand technique was high in rheumatoid
      patients even when being performed by experienced spine surgeons. Any guidance
      tools including navigation systems are recommended for placement of cervical PSs
      in patients with RA.

PMID- 25047654
TI  - Neck transfixion for sacral extradural spinal meningeal cysts without spinal
      nerve root fibers.
AB  - PURPOSE: This prospective study analyzes clinical characteristics and outcomes of
      sacral extradural spinal meningeal cysts (SESMC) without spinal nerve root fibers
      (SNRF) undergoing neck transfixion. METHODS: Using the relationship between the
      cysts and SNRF, SESMCs were divided into two types: cysts with SNRF known as
      Tarlov cysts and cysts without. If the SESMCs were identified as those without
      SNRFs, the neck of the cyst was transfixed, ligated and the remaining cyst wall
      removed distal to the clip. The improved Japanese Orthopedic Association (IJOA)
      scoring system was used to evaluate preoperative and postoperative neurological
      functions of the patients. RESULTS: Twenty-seven patients were included in this
      study. The average age was 42.7 +/- 11.93 years. The mean preoperative IJOA score
      was 17.5 +/- 2.47, and postoperative IJOA score was 19.1 +/- 1.41. The difference
      between preoperative and postoperative IJOA scores was statistically significant
      (t = -3.75, P = 0.001), with a significant improvement in neurological function
      after surgery. Among the improvements in neurological function, the most
      significant was bowel/bladder function (z = -2.33, P = 0.02). CONCLUSION: Most
      patients experienced significant improvement in their neurological function after
      surgery. The most significant area of neurological improvement was bowel/bladder
      dysfunction, however, preoperative stool or urine incontinence did not recover
      completely.

PMID- 25047655
TI  - SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1
      activation in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the fifth most common solid cancer worldwide.
      Sorafenib, a small multikinase inhibitor, is the only approved therapy for
      advanced HCC. The clinical benefit of sorafenib is offset by the acquisition of
      sorafenib resistance. Understanding of the molecular mechanism of STAT3
      overexpression in sorafenib resistance is critical if the clinical benefits of
      this drug are to be improved. In this study, we explored our hypothesis that loss
      of RFX-1/SHP-1 and further increase of p-STAT3 as a result of sorafenib treatment
      induces sorafenib resistance as a cytoprotective response effect, thereby,
      limiting sorafenib sensitivity and efficiency. We found that knockdown of RFX-1
      protected HCC cells against sorafenib-induced cell apoptosis and SHP-1 activity
      was required for the process. SC-2001, a molecule with similar structure to
      obatoclax, synergistically suppressed tumor growth when used in combination with
      sorafenib in vitro and overcame sorafenib resistance through up-regulating RFX-1
      and SHP-1 resulting in tumor suppression and mediation of dephosphorylation of
      STAT3. In addition, sustained sorafenib treatment in HCC led to increased p-STAT3
      which was a key mediator of sorafenib sensitivity. The combination of SC-2001 and
      sorafenib strongly inhibited tumor growth in both wild-type and sorafenib
      resistant HCC cell bearing xenograft models. These results demonstrate that
      inactivation of RFX/SHP-1 induced by sustained sorafenib treatment confers
      sorafenib resistance to HCC through p-STAT3 up-regulation. These effects can be
      overcome by SC-2001 through RFX-1/SHP-1 dependent p-STAT3 suppression. In
      conclusion, the use of SC-2001 in combination with sorafenib may constitute a new
      strategy for HCC therapy. 

PMID- 25047656
TI  - Terrestrial contributions to the aquatic food web in the middle Yangtze River.
AB  - Understanding the carbon sources supporting aquatic consumers in large rivers is
      essential for the protection of ecological integrity and for wildlife management.
      The relative importance of terrestrial and algal carbon to the aquatic food webs
      is still under intensive debate. The Yangtze River is the largest river in China
      and the third longest river in the world. The completion of the Three Gorges Dam
      (TGD) in 2003 has significantly altered the hydrological regime of the middle
      Yangtze River, but its immediate impact on carbon sources supporting the river
      food web is unknown. In this study, potential production sources from riparian
      and the main river channel, and selected aquatic consumers (invertebrates and
      fish) at an upstream constricted-channel site (Luoqi), a midstream estuarine site
      (Huanghua) and a near dam limnetic site (Maoping) of the TGD were collected for
      stable isotope (delta13C and delta15N) and IsoSource analyses. Model estimates
      indicated that terrestrial plants were the dominant carbon sources supporting the
      consumer taxa at the three study sites. Algal production appeared to play a
      supplemental role in supporting consumer production. The contribution from C4
      plants was more important than that of C3 plants at the upstream site while C3
      plants were the more important carbon source to the consumers at the two impacted
      sites (Huanghua and Maoping), particularly at the midstream site. There was no
      trend of increase in the contribution of autochthonous production from the
      upstream to the downstream sites as the flow rate decreased dramatically along
      the main river channel due to the construction of TGD. Our findings, along with
      recent studies in rivers and lakes, are contradictory to studies that demonstrate
      the importance of algal carbon in the aquatic food web. Differences in system
      geomorphology, hydrology, habitat heterogeneity, and land use may account for
      these contradictory findings reported in various studies. 

PMID- 25047657
TI  - The treatment outcome of multiple myeloma patients ineligible for hematopoietic
      transplantation--a single institutional experience in Taiwan.
AB  - Multiple myeloma (MM) is characterized by the neoplastic proliferation of
      monoclonal plasma cells in the bone marrow and results in complications. In
      Taiwan, melphalan and several novel agents are used to treat myeloma patients who
      are not candidate for hematopoietic stem cell transplant (HSCT). This
      retrospective study aimed to evaluate the characteristics, treatment outcome, and
      prognostic factors of MM patients who were ineligible for HSCT at our institution
      from October 2000 until November 2012. A total of 101 MM patients were reviewed.
      The median age was 71.0 years, and median overall survival (OS) was 22.0 months.
      Most of patients were diagnosed as IgG-type myeloma (55.4 %). The initial
      presentations included anemia (89.1 %), skeletal events (49.5 %), severe renal
      insufficiency (30.7 %), and hypercalcemia (28.7 %). With regard to the frontline
      therapy, thalidomide/steroid was the most common. Infection was the leading cause
      of death and adverse effects. Treatment with bortezomib, almost in the second- or
      third-line setting, was associated with longer median OS (35.5 months) and the
      median time to progression (TTP) (6.0 months). Bortezomib treatment,
      chemotherapy, International Staging System (ISS) stage I, and better performance
      status significantly correlated with survival benefit. In the bortezomib-treated
      subgroup, better treatment response caused excellent median OS (67.7 months) and
      also significantly delayed TTP. Therefore, this current analysis concluded a
      median OS of 22 months in myeloma patients ineligible for HSCT at our institution
      during the past 10 years. The use of bortezomib with better treatment response
      also achieved significantly better median OS and TTP. 

PMID- 25047659
TI  - Use of a web-based survey to facilitate shared decision making for patients
      eligible for cancer screening.
AB  - OBJECTIVE: Our aim was to facilitate shared decision making (SDM) during
      preventive visits by utilizing a web-based survey system to offer colorectal
      cancer (CRC) and prostate cancer screening decision aids (DAs) to appropriately
      identified patients prior to the visit. METHODS: Patients completed a web-based
      questionnaire before their preventive medicine appointment. Age- and gender
      appropriate patients completed additional questions to determine eligibility for
      CRC or prostate-specific antigen (PSA) screening. Eligible patients were offered
      a choice of video or print DA, and completed questions assessing their knowledge,
      values, and preferences regarding the screening decision. Responses were
      summarized and fed forward to clinician and patient reports. RESULTS: Overall,
      11,493 CRC and 4,384 PSA questionnaires were completed. Patient responses were
      used to identify those eligible for cancer-screening DAs: 2,187 (19 %) for CRC
      and 2,962 (68 %) for PSA; 15 % of eligible patients requested a DA. Many patients
      declined a DA because they indicated they "already know enough to make their
      decision" (34 % for CRC, 46 % for PSA). CONCLUSION: A web-based questionnaire
      provides an efficient means to identify patients eligible for cancer screening
      decisions and to offer them DAs before an appointment. Pre-visit use of DAs along
      with reports giving feedback to patients and clinicians provides an opportunity
      for SDM to occur at the visit.

PMID- 25047658
TI  - Sleep disturbance, depression and pain in adults with sickle cell disease.
AB  - BACKGROUND: Sleep disturbance and depression are commonly encountered in primary
      care. In sickle cell disease, depression is associated with pain, poor treatment
      compliance, and lower quality of life. The prevalence of sleep disturbance and
      its effect upon quality of life in adults with sickle cell disease is unknown.
      The goal of this study was to determine the prevalence of sleep disturbance and
      if it is associated with pain and depression in sickle cell disease. METHODS:
      Three hundred twenty eight adults with sickle cell disease enrolled on the
      Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep
      Quality Index and Beck Depression Inventory II screening measures as a cross
      sectional survey. Scores greater than 5 (Pittsburgh Sleep Quality Index) and 16
      (Beck Depression Inventory II) defined sleep disturbance and depression,
      respectively. Clinical and laboratory parameters were also assessed. RESULTS: The
      mean Pittsburgh Sleep Quality Index score was 8.4 (SD +/- 4.2) indicating a 71.2%
      prevalence of sleep disturbance. The mean Beck Depression Inventory II score was
      8.0 (SD +/- 8.9). Sixty five (20.6%) participants had a score indicating
      depression, and half of these (10.0%) had thoughts of suicide. Both Pittsburgh
      Sleep Quality Index and Beck Depression Inventory II scores were significantly
      correlated (p < .001). The number of days with mild/moderate pain (p = .001) and
      a history of headaches (p = .005) were independently associated with depression
      by multivariate regression analysis. Patients with sleep disturbance were older
      (p = .002), had higher body mass index (p = .011), had more days of pain (p =
      .003) and more frequent severe acute painful events (emergency room visits and
      hospitalizations) during the previous 12 months (p < .001). CONCLUSIONS: More
      than 70 percent of adults with sickle cell disease had sleep disturbance, while
      21 percent showed evidence of clinical depression. Sleep disturbance and
      depression were correlated, and were most common among those with more frequent
      pain. Providers caring for adults with sickle cell disease and frequent pain
      should consider screening for these common co-morbidities. Additional study is
      needed to confirm these findings and to determine if treatments for pain,
      depression or sleep disturbances will improve quality of life measures in this
      patient population. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT00011648.

PMID- 25047660
TI  - KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in
      lung cancer.
AB  - BACKGROUND: Lung cancer in nonsmokers tends to be driven by a single somatic
      mutation or a gene fusion. KIF5B-RET fusion is an oncogene identified in non
      small cell lung cancers. In this study, we verified the oncogenic activity of
      KIF5B-RET fusion and investigated how KIF5B-RET activates the specific signaling
      pathways for cellular transformation. We aimed to provide a basis for the further
      development of the therapy for KIF5B-RET positive lung cancer patients. METHODS:
      RT-PCR was used to screen for KIF5B-RET fusions in Chinese lung cancer patients.
      To verify the oncogenic activity of KIF5B-RET kinase in lung cancer cells, we
      manipulated its expression genetically followed by colony formation and tumor
      formation assays. The mechanism by which KIF5B-RET kinase induces proliferation
      was investigated by western blot, coimmunoprecipitation, and administration of
      RET, MAPK and STAT3 inhibitors. RESULTS: Our study identified a KIF5B-RET fusion
      in Chinese NSCLC patients and demonstrated that KIF5B-RET transfected cells
      showed a significantly increased proliferation rate and colony-forming ability.
      Furthermore, we found that KIF5B-RET fusion kinase induced multilevel activation
      of STAT3 at both Tyr705 and Ser727, and KIF5B-RET-STAT3 signaling related
      inhibitors repressed the proliferation and tumorigenicity of lung cancer cells
      significantly. CONCLUSIONS: Our data suggest that KIF5B-RET promotes the cell
      growth and tumorigenicity of non-small cell lung cancers through multilevel
      activation of STAT3 signaling, providing possible strategies for the treatment of
      KIF5B-RET positive lung cancers.

PMID- 25047661
TI  - A novel function of controlled-release nitrogen fertilizers.

PMID- 25047664
TI  - Cost-of-illness studies of atrial fibrillation: methodological considerations.
AB  - Atrial fibrillation (AF) is the most common heart rhythm arrhythmia, which has
      considerable economic consequences. This study aims to identify the current cost
      of-illness estimates of AF; a focus was put on describing the studies'
      methodology. A literature review was conducted. Twenty-eight cost-of-illness
      studies were identified. Cost-of-illness estimates exist for health insurance
      members, hospital and primary care populations. In addition, the cost of stroke
      in AF patients and the costs of post-operative AF were calculated. The methods
      used were heterogeneous, mostly studies calculated excess costs. The identified
      annual excess costs varied, even among studies from the USA (~US$1900 to
      ~US$19,000). While pointing toward considerable costs, the cost-of-illness
      studies' relevance could be improved by focusing on subpopulations and treatment
      mixes. As possible starting points for subsequent economic studies, the
      methodology of cost-of-illness studies should be taken into account using
      methods, allowing stakeholders to find suitable studies and validate estimates. 

PMID- 25047665
TI  - Human papillomavirus infection in Bhutan at the moment of implementation of a
      national HPV vaccination programme.
AB  - BACKGROUND: Cervical cancer is the most common female cancer in Bhutan, the first
      low/middle-income country to implement a national human papillomavirus (HPV)
      vaccination programme. METHODS: To provide a robust baseline for future
      evaluations of vaccine effectiveness, cervical cell specimens were obtained from
      2,505 women aged 18-69 years from the general population, and biopsies from 211
      cervical intraepithelial neoplasia grade 3 (CIN3) and 112 invasive cervical
      cancer (ICC) cases. Samples were tested for HPV using GP5+/6+ PCR. RESULTS: Among
      the general population, HPV prevalence was 26%, being highest (33%) in women <=24
      years, but remaining above 15% in all age-groups. Determinants of HPV included
      age, marital status, and number of sexual partners. Among the eight percent with
      cytological abnormalities, 24 CIN3 and 4 ICC were histologically confirmed. Even
      after additional testing with a sensitive E7 PCR, no infections with vaccine
      targeted HPV types were detected in the few vaccinated women (n = 34) compared to
      6% prevalence in unvaccinated women of similar age (p = 0 . 215). CONCLUSION:
      Based upon type-specific prevalence among biopsies, at least 70% of ICC in Bhutan
      are theoretically preventable by HPV16/18 vaccination, but screening programmes
      should be expanded among older women, who have an important underlying burden of
      CIN3 and ICC.

PMID- 25047666
TI  - Orally administered delta opioid agonist peptide rubiscolin-6 stimulates food
      intake in aged mice with ghrelin resistance.
AB  - SCOPE: It is known that a decline in food intake occurs with aging. In this
      study, we investigated changes in parameters associated with food intake in
      response to aging, and whether orexigenic peptides stimulated food intake after
      peripheral administration even in aged mice. METHODS AND RESULTS: Food intake and
      body weight of 27-month-old male C57BL/6N mice were lower than those of 15-month
      old mice. Epididymal and mesenteric fat mass, blood glucose, triglyceride, and
      leptin levels were also decreased. Meanwhile, the hypothalamic mRNA expression of
      endogenous orexigenic peptides such as neuropeptide Y (NPY) and agouti-related
      protein, also called agouti-related peptide, was increased. Next, we tested
      responsiveness to exogenously administered orexigenic peptides coupled to NPY in
      aged as well as young mice. Orally administered rubiscolin-6, a delta opioid
      agonist hexapeptide derived from a major green leaf protein Rubisco, stimulated
      food intake in 27-month-old mice. In contrast, ghrelin was ineffective after
      intraperitoneal administration to aged mice, suggesting that the NPY system
      downstream of ghrelin but not delta opioid receptors might be impaired in aged
      mice. CONCLUSION: Orally administered rubiscolin-6 stimulates food intake in aged
      mice with ghrelin resistance.

PMID- 25047667
TI  - Milder course in Duchenne patients with nonsense mutations and no muscle
      dystrophin.
AB  - Duchenne muscular dystrophy (DMD), a severe and lethal condition, is caused by
      the absence of muscle dystrophin. Therapeutic trials aiming at the amelioration
      of muscle function have been targeting the production of muscle dystrophin in
      affected Duchenne patients. However, how much dystrophin is required to rescue
      the DMD phenotype remains an open question. We have previously identified two
      exceptional golden retriever muscular dystrophy (GRMD) dogs with a milder course
      despite the total absence of muscle dystrophin. Here we report two unusual
      patients carrying nonsense mutations in the DMD gene and dystrophin deficiency
      but with an unexpectedly mild phenotype. Three reported polymorphisms,
      respectively in genes LTBP4, SPP1 and ACTN3 were excluded as possible DMD genetic
      modifiers in our patients. Finding the mechanisms that protect some rare patients
      and dogs from the deleterious effect of absent muscle dystrophin is of utmost
      importance and may lead to new avenues for treatment. Importantly, these
      observations indicate that it is possible to have a functional large muscle even
      without dystrophin. 

PMID- 25047669
TI  - Screening for late-onset Pompe disease in Finland.
AB  - Pompe disease (glycogen storage disease type II) is caused by autosomal recessive
      mutations in GAA gene. The estimated frequency of late-onset Pompe disease is
      around 1:60,000. However, only two infantile and one late-onset Pompe patients
      have been reported in Finland with a population of 5 million. We screened for
      late-onset Pompe disease in a cohort of undetermined myopathy patients with
      proximal muscle weakness and/or elevated serum creatine kinase values. Acid alpha
      glucosidase (GAA) activity in dried blood spots was measured and clinical data
      collected in 108 patients. Four patients had low normal GAA activity; all the
      others had activities well within the normal range. Re-analyses of these patients
      did not reveal new Pompe patients. Our findings suggest that Pompe disease is
      extremely rare in Finland. Finland is an example of an isolated population with
      enrichment of certain mutations for genetic disorders and low occurrence of some
      autosomal recessive diseases. 

PMID- 25047670
TI  - The influence of storage parameters on measurement of survival motor neuron (SMN)
      protein levels: implications for pre-clinical studies and clinical trials for
      spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is caused by low levels of survival motor neuron
      (SMN) protein. A growing number of potential therapeutic strategies for SMA are
      entering pre-clinical and clinical testing, including gene therapy and antisense
      oligonucleotide-based approaches. For many such studies SMN protein levels are
      used as one major readout of treatment efficacy, often necessitating comparisons
      between samples obtained at different times and/or using different protocols.
      Whether differences in tissue sampling strategies or storage parameters have an
      influence on measurable SMN levels remains to be determined. We assessed murine
      SMN protein immunoreactivity over time and under differing tissue storage
      conditions. SMN protein levels, measured using sensitive quantitative fluorescent
      western blotting, declined rapidly over a period of several days following sample
      collection, especially when protein was extracted immediately and stored at -20
      degrees C. Storage of samples at lower temperatures (-80 degrees C), and as
      intact tissue, led to significantly better preservation of SMN immunoreactivity.
      However, considerable deterioration in measurable SMN levels occurred, even under
      optimal storage conditions. These issues need to be taken into consideration when
      designing and interpreting pre-clinical and clinical SMA studies where SMN
      protein levels are being measured. 

PMID- 25047668
TI  - Early onset and novel features in a spinal and bulbar muscular atrophy patient
      with a 68 CAG repeat.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease
      caused by a trinucleotide (CAG) repeat expansion in the androgen receptor gene.
      Patients with SBMA have weakness, atrophy, and fasciculations in the bulbar and
      extremity muscles. Individuals with CAG repeat lengths greater than 62 have not
      previously been reported. We evaluated a 29year old SBMA patient with 68 CAGs who
      had unusually early onset and findings not seen in others with the disease.
      Analysis of the androgen receptor gene confirmed the repeat length of 68 CAGs in
      both peripheral blood and fibroblasts. Evaluation of muscle and sensory function
      showed deficits typical of SBMA, and in addition the patient had manifestations
      of autonomic dysfunction and abnormal sexual development. These findings extend
      the known phenotype associated with SBMA and shed new insight into the effects of
      the mutated androgen receptor. 

PMID- 25047671
TI  - [Pristinamycin/Vitamin k antagonists drug interaction: a French pharmacovigilance
      database study].
AB  - OBJECTIVE: To analyse pristinamycin/vitamin K antagonists (VKA) drug interaction
      by using data recorded in the French pharmacovigilance database (FPVB). METHODS:
      All cases with an increase effect of a VKA and an association with pristinamycin
      recorded in the FPVB between 1985 and 2013 were included. Data concerning
      patients, VKA treatments and side effects were recorded for a descriptive
      analysis. RESULTS: During this period, 31 reports with a VKA overdose after an
      association with pristinamycin were included. Fluindione is the most often
      involved VKA (77% of cases). In 20 cases (65.4%), VKA overdose caused bleeding
      and 24 cases (77.4%) were serious. CONCLUSION: Although mechanism is unknown,
      pristinamycine/AVK drug interaction is a reality that needs to be reported in the
      summary of product characteristics of these drugs and better known by
      practitioners to act in patients' interest.

PMID- 25047672
TI  - [Gabapentin-induced cutaneous leukocytoclastic vasculitis].
AB  - We describe the case of a woman who developed a cutaneous leukocytoclastic
      vasculitis following a treatment with gabapentine.

PMID- 25047673
TI  - [Medical treatment of the elderly in residential care: a multicenter cross
      sectional study].
AB  - OBJECTIVE: To retrospectively assess the quality of prescriptions in elderly
      patients prior the distribution of guidelines for geriatric drug prescriptions.
      METHODS: A cross-sectional study was conducted for one day in 2012 to investigate
      the quality of the prescriptions in 495 residents of 8 nursing homes. A 6 items
      quality score was calculated, ranging from 0 (lowest quality) to 6 (highest
      quality). RESULTS: The median number of prescribed drugs was 8,5 per resident.
      Over a total of 4311 prescribed drugs, the average quality score was 4,96 +/-
      0,45; 4,54 +/- 0,70 in computerized orders and 3,4 +/- 1,02 in handwritten
      orders. Among 939 drugs considered as at high risk of inducing serious adverse
      reactions, monitoring was prescribed 154 times only (16,4%). CONCLUSIONS: A lack
      of drug monitoring was highlighted, especially for high risk drugs. The quality
      of prescription may be improved by the use of computerized orders.

PMID- 25047674
TI  - EGFR-mutated lung cancer in Li-Fraumeni syndrome.
AB  - This is a revised case report of a 52 year old Caucasian female with Li-Fraumeni
      syndrome with a rare TP53 mutation, who was treated for breast cancer and later
      developed epidermal growth factor receptor (EGFR) mutated non-small cell lung
      cancer.

PMID- 25047675
TI  - Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in
      patients with advanced malignant pleural mesothelioma.
AB  - BACKGROUND: CBP501, a synthetic duodecapeptide, increases cisplatin influx into
      tumor cells through an interaction with calmodulin enhancing cisplatin
      cytotoxicity, and effects cell cycle progression by abrogating DNA repair at the
      G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with
      cisplatin, the most common toxicity was infusion-related urticaria. Activity of
      CBP501 plus cisplatin was observed in patients with ovarian cancer and
      mesothelioma, including some patients previously treated with cisplatin. METHODS:
      Chemotherapy naive patients with unresectable MPM were stratified by histology
      and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501
      25mg/m(2) IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint
      was progression free survival (PFS) at 4 months. RESULTS: 65 patients were
      randomized, and 63 were treated. Patient characteristics in the two arms were
      balanced. Based on independent radiology review of the treated population, 25/40
      patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS>=4mo; the median PFS was
      5.1mo (95% CI, 3.9, 6.5) vs 3.4mo (2.5, 6.7). Median OS was 13.3mo (9.2, 16.3) in
      Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than
      expected from standard chemotherapy, and comparable in the two arms, aside from
      infusion reactions which occurred in 70% of patients treated with CBP501.
      CONCLUSIONS: While this randomized phase II trial met its primary endpoint of PFS
      at 4 months, other parameters such as response rate and overall survival suggest
      that the addition of CBP501 does not improve the efficacy of standard
      chemotherapy for MPM.

PMID- 25047676
TI  - HER2 status in lung adenocarcinoma: a comparison of immunohistochemistry,
      fluorescence in situ hybridization (FISH), dual-ISH, and gene mutations.
AB  - OBJECTIVES: While novel anti-human epidermal growth factor receptor 2 (HER2)
      agents have recently been developed, no definite criteria have been proposed as
      indications for the use of these agents in patients with lung cancer. Here, we
      tested HER2 alterations by using four methods and explored the concordance of
      these methods to improve our understanding of the accuracy of HER2 testing
      methods. MATERIALS AND METHODS: We analyzed HER2 protein expression by
      immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ
      hybridization (FISH) and dual in situ hybridization (DISH) by using a tissue
      microarray comprising lung adenocarcinoma specimens from 243 consecutive
      patients. The presence of mutations in the EGFR, KRAS, and HER2 genes were also
      determined. RESULTS: Positive IHC (score 3+) was observed in six cases (2.5%).
      Amplification of HER2 was observed in five cases (2.1%) by FISH and in nine cases
      (3.7%) by DISH. HER2 expression by IHC and gene amplification by FISH were
      significantly associated (P<0.001). The overall concordance between FISH and DISH
      by amplification status was 96.7% (P<0.001). One hundred nine tumors (49.9%) had
      EGFR mutations, 25 (11.2%) had KRAS mutations, and six (2.7%) had HER2 mutations.
      All of these mutations were mutually exclusive. Cases having HER2 mutations were
      positively correlated with cases having HER2 amplification (P<0.001). Two of six
      cases with HER2 mutations showed amplifications by FISH and DISH tests.
      CONCLUSION: HER2 protein overexpression, gene amplification, and gene mutations
      appeared to be uncommon in lung adenocarcinoma. Cases with HER2 mutations tended
      to show HER2 gene amplification. The results indicated that HER2 gene
      amplification and mutations should be tested to determine whether patients are
      eligible for administration of new anti-HER2 agents. In addition, DISH was better
      than FISH for detection of cases with HER2 amplification.

PMID- 25047677
TI  - Oral bisphosphonate use and total knee/hip implant survival: validation of
      results in an external population-based cohort.
AB  - OBJECTIVE: Aseptic loosening is the most common cause of revision arthroplasty.
      Bisphosphonates could minimize this through their antiresorptive effects. This
      study was undertaken to investigate the association between bisphosphonate use
      and implant survival. METHODS: A retrospective cohort study was conducted within
      the Danish nationwide registries (5.5 million residents). Using procedure codes
      of the International Statistical Classification of Diseases and Related Health
      Problems, Tenth Revision, we identified patients age >=40 years undergoing total
      joint replacement in 1998-2007. We excluded users of disease-modifying
      antirheumatic drugs as well as patients with rheumatoid arthritis, Paget's
      disease, or hip fracture. Participants were classified as bisphosphonate users if
      they had been receiving treatment for >=6 months. A time-varying exposure was
      used to avoid immortal time bias. Up to 6 bisphosphonate nonusers undergoing
      arthroplasty were matched to each bisphosphonate user, using propensity scores.
      Stratified Cox regression was performed to model implant survival according to
      bisphosphonate use. Further, we studied the associations of implant survival with
      duration of use, adherence (medication possession ratio), and timing of therapy
      initiation (preoperative/postoperative). RESULTS: Of 95,392 patients with a
      primary total joint replacement, 80,342 (84.2%) were eligible. We identified
      1,590 bisphosphonate users (2.0%), and 1,558 of them (98.0%) were matched to
      8,966 bisphosphonate nonusers. Twenty-seven of the 1,558 bisphosphonate users
      (1.73%) and 399 of the 8,966 matched nonusers (4.45%) underwent revision surgery
      during the study followup period (at a median 2.61 years after the first surgery
      [interquartile range 1.04-5.41 years]). Cox regression showed a reduced risk of
      revision surgery in bisphosphonate users (hazard ratio 0.41 [95% confidence
      interval 0.27-0.61]). This association was strongest in patients with the longest
      duration of treatment and/or the best adherence. CONCLUSION: Oral bisphosphonate
      users have a 59% reduced risk of revision surgery. This association is only
      present when bisphosphonates are started after arthroplasty surgery. Confirmation
      in randomized controlled trials is urgently needed.

PMID- 25047678
TI  - Intramolecular C-F and C-H bond cleavage promoted by butadienyl heavy Grignard
      reagents.
AB  - Organomagnesium compounds (Grignard reagents) are among the most useful
      organometallic reagents and have greatly accelerated the advancement of synthetic
      chemistry and related sciences. Nevertheless, heavy Grignard reagents based on
      the metals calcium, strontium or barium are not widely used, mainly due to their
      rather inert heavy alkaline-earth metals and extremely high reactivity of their
      corresponding Grignard-type reagents. Here we report the generation and reaction
      chemistry of butadienyl heavy Grignard reagents whose extremely high reactivity
      is successfully tamed. Facile synthesis of perfluoro-pi-extended pentalene and
      naphthalene derivatives is realized by the in situ generated heavy Grignard
      reagents via intramolecular C-F/C-H bond cleavage. These obtained
      perfluorodibenzopentalene and perfluorodinaphthopentalene derivatives show low
      lying LUMO levels, with one being the lowest value so far among all pentalene
      derivatives. Our results set an exciting example for the meaningful synthetic
      application of heavy Grignard reagents. 

PMID- 25047679
TI  - Heat as a tracer for examining depth-decaying permeability in gravel deposits.
AB  - Depth dependence of permeability can appear in any geologic setting; however,
      vertical trends in alluvial gravel deposits are poorly understood because of the
      high variability of hydraulic conductivity K in monotonic sequences. This paper
      examines the sensitivity of depth-decaying permeability through heat transport
      simulation around a river's losing reach in the Toyohira River alluvial fan,
      Japan. Observed variations in groundwater temperature indicate that heat fluxes
      are dominant in the shallow zone, despite a vertical hydraulic gradient. In eight
      cases with different conditions (presence or absence of exponential decay trend,
      large or small variogram range, and cell isotropy or anisotropy) 1000 K
      realizations are stochastically generated throughout a cross-sectional model. The
      groundwater flow and heat transport are transiently calculated, and the averaged
      root mean square error RMSE? is used for sensitivity comparison. The variance of
      RMSE? shows that small RMSE? realizations are effectively reproduced with
      vertical trend assumed. Plausible realizations of RMSE? below a given threshold
      were obtained only when a vertical trend was assumed. The most plausible
      realization almost completely matched the observations. However, the number of
      plausible realizations per case was <=10 and the median RMSE? were insensitive to
      all the conditions. Statistical testing suggested that these plausible
      realizations may be statistically significant, aiding in generating a connected K
      zone for high heat flows. The cell anisotropy condition had the smallest effect
      on the simulation. Thus, effective modeling of the vertical trend contributes to
      heat transport; however, the model's efficiency is low without detailed
      information about the sedimentary structure. 

PMID- 25047680
TI  - Ellagic acid modulates the expression of oral innate immune mediators: potential
      role in mucosal protection.
AB  - BACKGROUND: Ellagic acid (EA) found in various fruits such as pomegranates,
      blackberries, raspberries, strawberries, and walnuts has different
      pharmacological functions including antioxidant, antitumor, antiallergic, anti
      inflammatory, antibacterial, and antiviral activities. It is not known, however,
      if EA could enhance mucosal innate immunity. Our goal was to determine the
      effects of EA on the expression of innate immune mediators produced by oral
      epithelial cells. METHODS: Culture of primary human gingival epithelial cells
      (HGEs) was performed in duplicate, and after the primary HGEs had been treated
      with EA at a concentration ranging from 12.5 to 100 MUM for 18 h the cells and
      supernatants were harvested. The expression of innate immune mediators including
      human beta-defensin 2 (hBD2), secretory leukocyte protease inhibitor (SLPI), and
      various cytokines and chemokines was measured at both transcriptional and
      translational levels by using quantitative real-time PCR, ELISA, and Luminex
      assay. RESULTS: In the presence of EA, the expression of hBD2-and SLPI mRNA was
      3.7-folds and 2.6-folds greater than untreated controls, respectively, and
      consistent with their secreted protein levels. For cytokines and chemokines,
      increased expression of RANTES, IL-2, and IL-1beta was found in response to EA.
      In contrast, EA decreased the expression of IL-6, IL-8, and TNF-alpha.
      CONCLUSIONS: This study demonstrated that oral innate immunity is affected by EA
      found in fruits. Thus, it may play some roles in mucosal innate immunity. The
      potential of EA for modulating the innate immune mediators may lead to developing
      a new topical agent to treat and/or prevent immune-mediated oral diseases.

PMID- 25047681
TI  - Doxepin for insomnia: a systematic review of randomized placebo-controlled
      trials.
AB  - Doxepin, a sedating tricyclic drug, at 3 mg and 6 mg doses was recently approved
      by the U.S. food and drug administration (FDA) for the treatment of insomnia. The
      objective of this systematic review was to obtain a precise summary of the
      efficacy and safety of doxepin as a hypnotic. We searched key databases and trial
      registers up to March 2014 and contacted pharmaceutical companies and the FDA for
      unpublished data. A total of nine randomized placebo-controlled trials were
      analyzed. Six studies were on doxepin 1-6 mg/d, two on doxepin 25-300 mg/d, and
      one on ramelteon 8 mg and doxepin 3 mg combined. All low-dose studies were
      industry-sponsored. We found that low-dose doxepin had a small to medium effect
      size against placebo for sleep maintenance and sleep duration but not for sleep
      initiation at both immediate and short-term posttreatment. There was no
      significant next-day residual effect with low-dose doxepin. Headache and
      somnolence were the most common side effects. We concluded that low-dose doxepin
      for 1-2 nights appeared to be safe and effective in improving sleep. However, a
      clear conclusion on its short-term benefits and risks as well as withdrawal
      effects was not possible due to the small number of studies. 

PMID- 25047682
TI  - Lineage grammars: describing, simulating and analyzing population dynamics.
AB  - BACKGROUND: Precise description of the dynamics of biological processes would
      enable the mathematical analysis and computational simulation of complex
      biological phenomena. Languages such as Chemical Reaction Networks and Process
      Algebras cater for the detailed description of interactions among individuals and
      for the simulation and analysis of ensuing behaviors of populations. However,
      often knowledge of such interactions is lacking or not available. Yet complete
      oblivion to the environment would make the description of any biological process
      vacuous. Here we present a language for describing population dynamics that
      abstracts away detailed interaction among individuals, yet captures in broad
      terms the effect of the changing environment, based on environment-dependent
      Stochastic Tree Grammars (eSTG). It is comprised of a set of stochastic tree
      grammar transition rules, which are context-free and as such abstract away
      specific interactions among individuals. Transition rule probabilities and rates,
      however, can depend on global parameters such as population size, generation
      count, and elapsed time. RESULTS: We show that eSTGs conveniently describe
      population dynamics at multiple levels including cellular dynamics, tissue
      development and niches of organisms. Notably, we show the utilization of eSTG for
      cases in which the dynamics is regulated by environmental factors, which affect
      the fate and rate of decisions of the different species. eSTGs are lineage
      grammars, in the sense that execution of an eSTG program generates the
      corresponding lineage trees, which can be used to analyze the evolutionary and
      developmental history of the biological system under investigation. These lineage
      trees contain a representation of the entire events history of the system,
      including the dynamics that led to the existing as well as to the extinct
      individuals. CONCLUSIONS: We conclude that our suggested formalism can be used to
      easily specify, simulate and analyze complex biological systems, and supports
      modular description of local biological dynamics that can be later used as "black
      boxes" in a larger scope, thus enabling a gradual and hierarchical definition and
      simulation of complex biological systems. The simple, yet robust formalism
      enables to target a broad class of stochastic dynamic behaviors, especially those
      that can be modeled using global environmental feedback regulation rather than
      direct interaction between individuals.

PMID- 25047683
TI  - Associations between body mass index and foot joint pain in middle-aged and older
      women: a longitudinal population-based cohort study.
AB  - OBJECTIVE: To investigate the relationship between body mass index (BMI) and foot
      joint pain (FJP) over a 5-year period in a community-based cohort. METHODS: We
      examined a subset of women from the Chingford Women's Study, a community cohort
      followed up for 20 years. From a baseline of 1,003 female participants, we
      reviewed data from 639 women (64%) for whom complete data sets for FJP and BMI
      were obtained over a 5-year period between year 10 (Y10) and year 15 (Y15).
      Descriptive statistics, binary regression modeling, and odds ratios (ORs) were
      used to examine the longitudinal relationship between BMI and FJP. RESULTS: For
      Y10 and Y15, the median age was 61 years (interquartile range [IQR] 57-67) and 66
      years (IQR 62-72), respectively, and the mean +/- SD BMI was 26.7 +/- 4.6 kg/m(2)
      and 27.2 +/- 4.8 kg/m(2) , respectively. FJP prevalence was 21.6% at Y10 and
      26.6% at Y15. Longitudinal analyses showed that both BMI and FJP increased
      significantly from Y10 to Y15 (P < 0.001). The odds of having FJP after a 5-year
      period increased by 4.9% for each BMI unit increase 5 years earlier (OR 1.049
      [95% confidence interval (95% CI) 1.011-1.089], P = 0.012). This remained
      significant when adjusted for age, diabetes mellitus, and rheumatoid arthritis
      (OR 1.051 [95% CI 1.011-1.091], P = 0.012). CONCLUSION: This is the first large
      longitudinal cohort study demonstrating that, in middle-aged women, a high BMI
      precedes and is predictive of FJP independent of age. Evidence from our findings
      can be used to identify those individuals at risk of developing FJP.

PMID- 25047684
TI  - HBV preS2 transactivates FOXP3 expression in malignant hepatocytes.
AB  - BACKGROUND & AIMS: Recent data reported the increased expression of forkhead box
      protein 3 (FOXP3), the well known master regulator of CD4(+) C25(+) regulatory T
      cells, in hepatocellular carcinoma (HCC) cells. However, the mechanisms remain
      unknown. We previously showed that preS2, one of important regulatory proteins
      encoded by HBV, triggers transactivation of hTERT in malignant hepatocytes. Here,
      we aimed to explore the role of preS2 in regulating FOXP3 expression in HCC.
      METHODS: FOXP3 expression was detected by RT-PCR, Western blot and
      immunohistochemical staining. Cotransfection and siRNA knockdown were involved to
      study the regulation effects of preS2 on FOXP3 expression in cultured HCC cell
      lines. Luciferase reporter assay and EMSA assay were performed to explore the
      mechanism of preS2-mediated FOXP3 upregulation. RESULTS: Immunohistochemical
      staining detected significant increased FOXP3 expression in malignant hepatocytes
      from sections of HCC patients. The total FOXP3 expression in hepatocytes from
      patients with HBsAg-positive HCC was significantly increased compared to that of
      HBV-negative HCCs (P = 0.002). In accordance, preS2 overexpression enhanced FOXP3
      expression in HCC cell lines, while preS2 knockdown significantly reduced FOXP3
      expression in HBV-integrated HepG2.2.15 cells. Results of cotransfection and
      luciferase report assay showed that preS2 transactivated FOXP3 promoter in a dose
      dependent manner. Further study identified the AP-1 binding site at 20 bp region
      from -465 bp to -445 bp of FOXP3 promoter was responsible for preS2-induced FOXP3
      transcriptional activation. CONCLUSIONS: Our data here, for the first time,
      provided direct evidence to demonstrate that preS2 oncoprotein encoded by HBV
      transactivated FOXP3 transcription in HCC cells.

PMID- 25047685
TI  - Brain correlates of response inhibition in Internet gaming disorder.
AB  - AIMS: The present study aimed to evaluate the brain correlates of response
      inhibition among subjects with Internet gaming disorder (IGD). METHODS: For this
      purpose, 15 men with IGD for at least 1 year, and 15 controls with no history of
      IGD were recruited to perform the Go/Nogo task under functional magnetic
      resonance imaging investigation. Prior to scanning, the subjects were assessed
      using the Chen Internet Addiction Scale and the Barrett Impulsivity Scale.
      RESULTS: The control group exhibited activation of the right supplement motor
      area (SMA), dorsolateral prefrontal cortex, and caudate for response inhibition.
      However, the IGD group had a higher impulsivity and lower activity of the right
      SMA/pre-SMA in comparison to the control group. CONCLUSIONS: The results obtained
      suggest that dysfunctional activation of the SMA for response inhibition is one
      of the candidate mechanisms of IGD.

PMID- 25047686
TI  - Role of cerebellum in deglutition and deglutition disorders.
AB  - The objective of this review is to gather available evidence regarding the role
      of the cerebellum in swallowing-related functions. We reviewed literature on
      cerebellar functions related to healthy swallowing, patterns of dysphagia in
      individuals with cerebellar lesions, and the role of the cerebellum in
      therapeutic intervention of neurogenic dysphagia since 1980. A collective
      understanding of these studies suggests that both hemispheres of the cerebellum,
      predominantly the left, participate in healthy swallowing. Also, it appears that
      the cerebellum contributes to specific physiological functions within the entire
      act of swallowing, but this is not clearly understood. The understanding of
      patterns of dysphagia in cerebellar lesions remains ambiguous with equivocal
      results across a small number of studies. The cerebellum appears to be involved
      in oral exercises for dysphagia in the relationship between oral movements in
      such exercises, and deglutition remains uncertain. There is increasing evidence
      to suggest successful use of transcranial magnetic stimulation of the cerebellum
      to improve neuromotor control of swallowing. Future studies should address
      activation of the cerebellum with swallowing of different consistencies and
      tastes in healthy adults to gain better insights. Studies should also investigate
      dynamics of neural activation during different stages of recovery from dysphagia
      following strokes to cortical centers to determine if the cerebellum plays a
      compensatory role during instances of increased neural demands. 

PMID- 25047688
TI  - Risk compensation following male circumcision: results from a two-year
      prospective cohort study of recently circumcised and uncircumcised men in Nyanza
      Province, Kenya.
AB  - We present the results of the first study of longitudinal change in HIV
      associated risk behaviors in men before and after circumcision in the context of
      a population-level voluntary medical male circumcision (VMMC) program. The
      behaviors of 1,588 newly circumcised men and 1,598 age-matched uncircumcised
      controls were assessed at baseline, 6, 12, 18 and 24 months of follow-up. Despite
      the precipitous decline in perception of high HIV risk among circumcised men (30
      14 vs. 24-21 % in controls) and increased sexual activity among the youngest
      participants (18-24 years; p-time < 0.0001, p-group = 0.96), all specific risk
      behaviors decreased over time similarly in both groups. The proportion of men
      reporting condom use at last sex increased for both groups, with a greater
      increase among circumcised men (30 vs. 6 %). We found no evidence of risk
      compensation in men following circumcision. Concerns about risk compensation
      should not impede the widespread scale-up of VMMC initiatives. 

PMID- 25047687
TI  - Partner age differences and concurrency in South Africa: Implications for HIV
      infection risk among young women.
AB  - Partner-age difference is an HIV-risk factor among young women in Africa, but the
      underlying mechanisms are poorly understood. We used nationally representative
      data among black South Africans (men: 3,530; women: 3,946) to examine the
      proportion of women in partnerships involving male partner concurrency by age of
      female partners and by age-disparate (>=5 years) partnerships. Of all partners
      reported by men, 35 % of young (16-24) women were in partnerships involving male
      partner concurrency of 4 weeks or longer during the past 12 months. Young women
      in age-disparate partnerships were more likely to be in partnerships with men who
      had other concurrent partners (9 %; OR 1.88 p < 0.01) and more likely to be
      connected to an older sexual network. Our results suggest that the relationship
      between male concurrency and age-disparate relationships may increase HIV risk
      for young women by connecting them to larger and older sexual networks.

PMID- 25047689
TI  - Unprecedented role of hydronaphthoquinone tautomers in biosynthesis.
AB  - Quinones and hydroquinones are among the most common cellular cofactors, redox
      mediators, and natural products. Here, we report on the reduction of 2
      hydroxynaphthoquinones to the stable 1,4-diketo tautomeric form of
      hydronaphthoquinones and their further reduction by fungal
      tetrahydroxynaphthalene reductase. The very high diastereomeric and enantiomeric
      excess, together with the high yield of cis-3,4-dihydroxy-1-tetralone, exclude an
      intermediary hydronaphthoquinone. Labeling experiments with NADPH and NADPD
      corroborated the formation of an unexpected 1,4-diketo tautomeric form of 2
      hydroxyhydronaphthoquinone as a stable intermediate. Similar 1,4-diketo tautomers
      of hydronaphthoquinones were established as products of the NADPH-dependent
      enzymatic reduction of other 1,4-naphthoquinones, and as substrates for different
      members of the superfamily of short-chain dehydrogenases. We propose an essential
      role of hydroquinone diketo tautomers in biosynthesis and detoxification
      processes. 

PMID- 25047690
TI  - Variation of DNA methylation in candidate age-related targets on the
      mitochondrial-telomere axis in cord blood and placenta.
AB  - BACKGROUND: Epigenetics is tissue-specific and potentially even cell-specific,
      but little information is available from human reproductive studies about the
      concordance of DNA methylation patterns in cord blood and placenta, as well as
      within-placenta variations. We evaluated methylation levels at promoter regions
      of candidate genes in biological ageing pathways (SIRT1, TP53, PPARG, PPARGC1A,
      and TFAM), a subtelomeric region (D4Z4) and the mitochondrial genome (MT-RNR1, D
      loop). METHODS: Ninety individuals were randomly chosen from the ENVIRONAGE birth
      cohort to evaluate methylation concordance between cord blood and placenta using
      highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen
      individuals, a more extensive sampling scheme was performed to examine within
      placenta variation. RESULTS: The DNA methylation levels of the subtelomeric
      region and mitochondrial genome showed concordance between cord blood and
      placenta with correlation coefficients ranging from r = 0.31 to 0.43, p <= 0.005,
      and also between the maternal and foetal sides of placental tissue (r = 0.53 to
      0.72, p <= 0.05). For the majority of targets, an agreement in methylation levels
      between four foetal biopsies was found (with intra-class correlation coefficients
      ranging from 0.16 to 0.72), indicating small within-placenta variation.
      CONCLUSIONS: The methylation levels of the subtelomeric region (D4Z4) and
      mitochondrial genome (MT-RNR1, D-loop) showed concordance between cord blood and
      placenta, suggesting a common epigenetic signature of these targets between
      tissues. Concordance was lacking between the other genes that were studied. In
      placental tissue, methylation patterns of most targets on the mitochondrial
      telomere axis were not strongly influenced by sample location.

PMID- 25047691
TI  - Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie
      2 is altered in pregnancies complicated by preeclampsia.
AB  - OBJECTIVE: To investigate the placental expression of angiopoietin (Ang)-1, Ang-2
      and their receptor, Tie-2, in preeclampsia (PE) with or without intrauterine
      growth restriction (IUGR). METHODS: Case-control study including placentas from
      28 PE pregnancies, 30 PE-IUGR pregnancies and 40 controls. The expression status
      of the genes was evaluated by quantitative real-time PCR. RESULTS: In both PE and
      PE-IUGR groups, compared to the control group, there was significantly higher
      expression of Ang-2 (p < 0.001) and Tie-2 (p = 0.008) and lower expression of Ang
      1 (p = 0.001). The magnitude of the difference was similar for Ang-1 for both
      groups, whereas the magnitude of the differences was higher for Ang-2 and Tie-2
      in PE-IUGR group compared to controls. Ang-2 and Tie-2 were correlated in both PE
      (r = 0.8602, p < 0.001) and PE-IUGR (r = 0.6342, p < 0.001) groups. In PE-IUGR
      group, Ang-1 was associated to Ang-2 (r = 0.3458, p = 0.0452) and Tie-2 (r =
      0.4448, p = 0.0084). Log10Ang-1 but not Ang-2 was gestational age dependent (R2 =
      0.40, p < 0.001). After conversion in Multiples of the Median (MoM) log10 MoM Ang
      1 was reduced in the PE group (mean = -0.8181, p < 0.001) and the PE-IUGR group
      (mean = -1.2583, p < 0.001) compared to control group (mean = -0.0924).
      DISCUSSION: We have demonstrated increased placental expression of Ang-2 and Tie
      2 along with lower expression levels of Ang-1 in pregnancies with PE and PE-IUGR.
      CONCLUSION: The angiopoietin axis seems to be disrupted in PE pregnancies.
      Whether the results of this study represent the angiogenic imbalance observed in
      PE pregnancies or they are part of the pathophysiology of this condition has to
      be further investigated.

PMID- 25047692
TI  - Mental health problems and educational attainment in adolescence: 9-year follow
      up of the TRAILS study.
AB  - BACKGROUND: This study examines if mental health problems at age 11 and changes
      in mental health problems between age 11 and 16 predict educational attainment of
      adolescents at age 19, overall and stratified by gender. METHODS: Data from 1711
      adolescents (76.8% from initial cohort) of the Tracking Adolescents' Individual
      Lives Survey (TRAILS), a Dutch prospective cohort study with 9 year follow-up,
      were used. Mental health problems (externalizing, internalizing and attention
      problems) were measured by the Youth Self Report and the Child Behavior Checklist
      at ages 11 and 16. Difference scores for mental health problems between age 11
      and 16 were calculated. Educational attainment was assessed at age 19. RESULTS:
      Externalizing, internalizing and attention problems at age 11 were significantly
      associated with low educational attainment at age 19 (crude model). When adjusted
      for demographic variables and the other mental health problems, only the
      association for attention problems remained significant (odds ratio (OR), 95%
      confidence interval: 3.19, 2.11-4.83). Increasing externalizing problems between
      age 11 and 16 also predicted low educational attainment at age 19 (OR 3.12, 1.83
      5.32). Among girls, increasing internalizing problems between age 11 and 16
      predicted low educational attainment (OR 2.21, 1.25-3.94). For boys, no
      significant association was found for increasing internalizing problems and low
      educational attainment. For increasing attention problems between age 11 and 16
      no significant association with low educational attainment was found.
      CONCLUSIONS: Externalizing, internalizing and attention problems at age 11 and an
      increase of these problems during adolescence predicted low educational
      attainment at age 19. Early treatment of these mental health problems may improve
      educational attainment, and reduce socioeconomic health differences in adulthood.

PMID- 25047693
TI  - The medico-legal aspects of prescribing vitamin D.
AB  - Vitamin D is a particularly important sterol hormone and its effects beyond bone
      are increasingly recognized. Over the last decade clinical interest has grown in
      vitamin D, with increased recognition of deficiency and hence increased
      prescribing of vitamin D products. However, the increased prescription of vitamin
      D has generally been met with unlicensed vitamin D products which potentially
      expose the patient to clinical risk. This review discusses the issues relating to
      the clinical use of unlicensed vitamin D products, safety concerns that may arise
      from this, as well as discussing the medico-legal responsibilities of the
      prescriber and dispenser. 

PMID- 25047694
TI  - Comments to Focardi et al., Age estimation for forensic purposes in Italy:
      ethical issues.

PMID- 25047695
TI  - Reply to the letter to the editor.

PMID- 25047696
TI  - Sexual dimorphism of the tibia in contemporary Greeks, Italians, and Spanish:
      forensic implications.
AB  - There are many population-specific studies around the world on sex estimation
      from skeletal remains. Of the long bones, the tibia has been an important one
      because it is commonly studied to assess population specificity of a long bone.
      However, the studies in Europe that use this bone for sex estimation remain
      limited. The aim of this study is to analyse the tibia in different populations
      of the southern Europe such as Greece, Italy, and Spain providing standards for
      sex estimation in a forensic context. In total, we analyzed tibiae of 157 Greek,
      190 Italian, and 105 Spanish individuals. Standard osteometric measurements were
      taken and the data was analyzed using discriminant function statistics. Posterior
      probabilities were calculated for all produced formulae. Statistical analysis was
      performed using SPSS subroutines. All measurements were significantly different
      between the sexes in all three populations and in the pooled sample. A
      discriminant function of the pooled sample for Southern Europeans resulted in
      about 88 % accuracy using all three variables. Over 43 % of the individuals were
      correctly classified at a 0.95 threshold. More work should be done including
      other Southern European populations to this database to further test the
      applicability of the method. 

PMID- 25047697
TI  - Mobility guidelines for high fill factor solution-processed small molecule solar
      cells.
AB  - Analysis of measured charge-carrier mobilities and fill factors in solution
      processable small-molecule bulk-heterojunction solar cells reveals that in order
      to achieve a high FF, the hole and electron mobilities must be >10(-4) cm 2 V(-1)
      s(-1) . Neat-film mobility measurements are also found to be a useful predictor
      of the maximum blend film mobility and FF obtained in blend film solar cells. 

PMID- 25047698
TI  - Plasma free fatty acids do not provide the link between obesity and insulin
      resistance or beta-cell dysfunction: results of the Reading, Imperial, Surrey,
      Cambridge, Kings (RISCK) study.
AB  - AIMS: To investigate the relationship between adiposity and plasma free fatty
      acid levels and the influence of total plasma free fatty acid level on insulin
      sensitivity and beta-cell function. METHODS: An insulin sensitivity index, acute
      insulin response to glucose and a disposition index, derived from i.v. glucose
      tolerance minimal model analysis and total fasting plasma free fatty acid levels
      were available for 533 participants in the Reading, Imperial, Surrey, Cambridge,
      Kings study. Bivariate correlations were made between insulin sensitivity index,
      acute insulin response to glucose and disposition index and both adiposity
      measures (BMI, waist circumference and body fat mass) and total plasma free fatty
      acid levels. Multivariate linear regression analysis was performed, controlling
      for age, sex, ethnicity and adiposity. RESULTS: After adjustment, all adiposity
      measures were inversely associated with insulin sensitivity index (BMI: beta = 
      0.357; waist circumference: beta = -0.380; body fat mass: beta = -0.375) and
      disposition index (BMI: beta = -0.215; waist circumference: beta = -0.248; body
      fat mass: beta = -0.221) and positively associated with acute insulin response to
      glucose [BMI: beta = 0.200; waist circumference: beta = 0.195; body fat mass beta
      = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in
      insulin sensitivity index, acute insulin response to glucose and disposition
      index, respectively. After adjustment, no adiposity measure was associated with
      free fatty acid level, but total plasma free fatty acid level was inversely
      associated with insulin sensitivity index (beta = -0.133), acute insulin response
      to glucose (beta = -0.148) and disposition index [beta = -0.218 (P values
      <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the
      variation in insulin sensitivity index, acute insulin response to glucose and
      disposition index, respectively. CONCLUSIONS: Plasma free fatty acid levels have
      a modest negative association with insulin sensitivity, beta-cell secretion and
      disposition index but no association with adiposity measures. It is unlikely that
      plasma free fatty acids are the primary mediators of obesity-related insulin
      resistance or beta-cell dysfunction.

PMID- 25047699
TI  - Spatulated end-to-end microvascular anastomosis: a useful technique for
      overcoming vessel size discrepancy.

PMID- 25047700
TI  - Endovascular revascularization and free tissue transfer for lower limb salvage.
AB  - Combined bypass surgery with free flap reconstruction is an established method
      for lower limb salvage. But the success of the combination of endovascular
      revascularization together with free tissue transfer has so far not been well
      established. A retrospective review of all patients who had undergone
      endovascular revascularization and reconstructed with free tissue transfer for
      lower limb salvage at Tzu Chi Dalin General Hospital between 2008 and 2012 was
      performed. A total of 26 legs underwent limb salvage in 24 patients. There were
      10 male and 14 female patients. Their average age was 71.4 years. The average
      time interval between endovascular intervention and free tissue transfer was 8
      days. There was 100% flap survival but partial flap necrosis was seen in three
      patients. A high rate of wound infection was seen in eight patients, all
      requiring further debridement. The total limb salvage rate at 1-year follow-up
      was 96% and 92% at the 2-year follow-up. In conclusion, the success rate of lower
      limb salvage using a combination of endovascular revascularization and free
      tissue reconstruction is comparable to using a combination of bypass surgery and
      free tissue transfer. It is associated with a high flap success rate and a high
      limb salvage rate. It provides physicians with a further treatment option in the
      management of ischemic lower limbs with extended tissue loss. 

PMID- 25047701
TI  - Combination of the superior and inferior pedicle "continuities" for anastomosis
      of an SIEA flap to a contralateral DIEP flap in double-pedicled abdominal free
      flaps: A further modification of the Hamdi classification.

PMID- 25047702
TI  - Intrathoracic tissue expanders for postpneumonectomy syndrome.

PMID- 25047703
TI  - Youth self-efficacy domains as predictors of change in routine community mental
      health services.
AB  - OBJECTIVE: This study examined how youth self-efficacy in four domains--Social,
      Academic Diligence, Academic Proficiency, and Behavioral Regulation--was
      associated with youth symptoms and psychotherapy outcomes. METHOD: Participants
      were 104 youth (aged 12-17, mean age 14.6) and their parents/guardians. Youth
      completed a measure of perceived self-efficacy and the Youth Outcome
      Questionnaire-Self-Report (YOQ-SR) regularly over the course of treatment;
      parents/guardians also completed the Youth Outcome Questionnaire. RESULTS:
      Although none of the self-efficacy domains significantly predicted changes in
      parent reports of symptoms, individual growth curve models indicated that
      increases in three of the four self-efficacy domains (Social, Academic Diligence,
      and Behavioral Regulation) over the course of treatment were associated with
      concurrent improvements in youth-reported symptoms. CONCLUSIONS: Results suggest
      that youth self-efficacy warrants further study in relation to change processes
      in youth mental health services.

PMID- 25047704
TI  - Detection of Neospora caninum-DNA in feces collected from dogs in Shenyang
      (China) and ITS1 phylogenetic analysis.
AB  - Neospora caninum is an intracellular protozoan that infects many domestic and
      wild animals. Dog is known as a definitive host of N. caninum and involved in
      transmitting infections to intermediate hosts by shedding oocysts. To investigate
      the epidemiology of dog neosporosis in China, 212 dog feces specimens in Shenyang
      were screened by nested-PCR using Nc5 primers and confirmed by N. caninum ITS1
      PCR. The positive rate of N. caninum DNA was 34.90% (74/212). There were no
      significant correlations in prevalence of Neospora infections between different
      ages and genders. N. caninum DNA positive samples were further examined by PCR
      using Hammondia heydorni-specific primers. 37 out of 74 N. caninum DNA positive
      samples were also H. heydorni DNA positive. Only Nc5 primers positive and H.
      heydorni primers negative samples were used for ITS1 gene sequence analysis.
      Sequencing results from the 37 N. caninum positive samples revealed that ITS1
      gene has 96-100% similarity with N. caninum sequences deposited in Genbank. Also,
      the presence of a new genotype indicated genetic polymorphism of N. caninum in
      infected dog feces in Shenyang of China.

PMID- 25047705
TI  - Pichia pastoris expressed EtMic2 protein as a potential vaccine against chicken
      coccidiosis.
AB  - Chicken coccidiosis caused by Eimeria species leads to tremendous economic losses
      to the avian industry worldwide. Identification of parasite life cycle specific
      antigens is a critical step in recombinant protein vaccine development against
      Eimeria infections. In the present study, we amplified and cloned the microneme-2
      (EtMIC2) gene from Eimeria tenella wild type strain SD-01, and expressed the
      EtMic2 protein using Pichia pastoris and Escherichia coli expression systems,
      respectively. The EtMic2 proteins expressed by P. pastoris and E. coli were used
      as vaccines to immunize chickens and their protective efficacies were compared
      and evaluated. The results indicated that both P. pastoris and E. coli expressed
      EtMic2 proteins exhibited good immunogenicity in stimulating host immune
      responses and the Pichia expressed EtMic2 provided better protection than the E.
      coli expressed EtMic2 did by significantly increasing growth rate, inducing high
      specific antibody response, reducing the oocyst output and cecal lesions.
      Particularly, the Pichia expressed EtMic2 protein exhibited much better ability
      in inducing cell mediated immune response than the E. coli expressed EtMic2. 

PMID- 25047707
TI  - Systematically defining single-gene determinants of response to neoadjuvant
      chemotherapy reveals specific biomarkers.
AB  - PURPOSE: We sought to systematically define determinants of the response to
      neoadjuvant chemotherapy to elucidate predictive biomarkers for breast cancer.
      EXPERIMENTAL DESIGN: An unbiased systematic analysis was performed in multiple
      independent datasets to define genes predictive of complete pathologic response
      (pCR) following treatment with neoadjuvant chemotherapy. These genes were
      interrogated across estrogen receptor (ER)-positive and ER-negative breast cancer
      and those in common across three different treatment regimens were analyzed for
      optimal predictive power. Subsequent validation was performed on independent
      cohorts by gene expression and IHC analyses. RESULTS: Genes that were highly
      associated with the response to neoadjuvant chemotherapy in breast cancer were
      readily defined using a computational method ranking individual genes by their
      respective ROC. Such predictive genes of the response to taxane-associated
      therapies were strongly enriched for cell-cycle control processes in both ER
      positive and ER-negative breast cancer and correlated with pCR. However, other
      genes that were specifically associated with residual disease were also
      identified under other treatment conditions. Using the intersection between
      treatment groups, nine genes were identified that harbored strong predictive
      power in multiple contexts and validation cohort. In particular, the nuclear
      oncogene DEK was strongly associated with pCR, whereas the cell surface protein
      BCAM was strongly associated with residual disease. By IHC staining, these
      markers exhibited potent predictive power that remained significant in
      multivariate analysis. CONCLUSION: Systematic computational approaches can define
      key genes that will be able to predict the response to chemotherapy across
      multiple treatment modalities yielding a small collection of biomarkers that can
      be readily deployed by IHC analyses.

PMID- 25047708
TI  - Evolutionary constraints or opportunities?
AB  - Natural selection is traditionally viewed as a leading factor of evolution,
      whereas variation is assumed to be random and non-directional. Any order in
      variation is attributed to epigenetic or developmental constraints that can
      hinder the action of natural selection. In contrast I consider the positive role
      of epigenetic mechanisms in evolution because they provide organisms with
      opportunities for rapid adaptive change. Because the term "constraint" has
      negative connotations, I use the term "regulated variation" to emphasize the
      adaptive nature of phenotypic variation, which helps populations and species to
      survive and evolve in changing environments. The capacity to produce regulated
      variation is a phenotypic property, which is not described in the genome.
      Instead, the genome acts as a switchboard, where mostly random mutations switch
      "on" or "off" preexisting functional capacities of organism components. Thus,
      there are two channels of heredity: informational (genomic) and structure
      functional (phenotypic). Functional capacities of organisms most likely emerged
      in a chain of modifications and combinations of more simple ancestral functions.
      The role of DNA has been to keep records of these changes (without describing the
      result) so that they can be reproduced in the following generations. Evolutionary
      opportunities include adjustments of individual functions, multitasking,
      connection between various components of an organism, and interaction between
      organisms. The adaptive nature of regulated variation can be explained by the
      differential success of lineages in macro-evolution. Lineages with more
      advantageous patterns of regulated variation are likely to produce more species
      and secure more resources (i.e., long-term lineage selection). 

PMID- 25047706
TI  - Molecular pathways: myeloid complicity in cancer.
AB  - Cancer-induced inflammation results in accumulation of myeloid cells. These
      myeloid cells include progenitors and progeny of monocytes, granulocytes,
      macrophages, and dendritic cells. It has become increasingly evident that tumor
      dependent factors can condition myeloid cells toward an immunosuppressive and
      protumorigenic phenotype. Thus, myeloid cells are not simply bystanders in
      malignancy or barometers of disease burden. Reflecting their dynamic and plastic
      nature, myeloid cells manifest a continuum of cellular differentiation and are
      intimately involved at all stages of neoplastic progression. They can promote
      tumorigenesis through both immune-dependent and -independent mechanisms and can
      dictate response to therapies. A greater understanding of the inherent plasticity
      and relationships among myeloid subsets is needed to inform therapeutic
      targeting. New clinical trials are being designed to modulate the activities of
      myeloid cells in cancer, which may be essential to maximize the efficacy of both
      conventional cytotoxic and immune-based therapies for solid tumors. Clin Cancer
      Res; 20(20); 5157-70. (c)2014 AACR. 

PMID- 25047710
TI  - No association found between cardiovascular mortality, and job demands and
      decision latitude: experience from the Vasterbotten Intervention Programme in
      Sweden.
AB  - The current prospective study with the longest follow-up period in Northern
      Sweden aims to investigate the association between job demands and decision
      latitude and cardiovascular disease (CVD) mortality. Further, we aim to assess
      the effect of conventional risk factors (i.e., body mass index, alcohol
      consumption, physical activity, marital status, education and smoking) on the
      association between job demands and decision latitude and CVD mortality. The data
      originated from the Linnaeus database, available at the Center for Population
      Studies, Umea University, Sweden. A cohort of men and women aged 40, 50 and 60
      years were recruited from the Vasterbotten Intervention Programme. Deaths due to
      stroke and myocardial infarction at the end of the follow up are considered the
      outcome. Baseline job characteristics were defined by the Swedish version of the
      Karasek demand/control model. Statistical methods include proportional Cox hazard
      modeling and Relative Excess Risk due to Interaction (RERI) to assess
      interactions. The findings from this study did not support the association
      between job demands and decision latitude and CVD mortality. Instead,
      conventional risk factors were found stronger predictors, most evidently
      education differentials were associated with CVD mortality. We know from previous
      research that the greater the attenuation of the gradient after adjustment for a
      given risk factor, the greater the potential to reduce educational inequality via
      interventions that target this factor. Based on the present findings of the
      experience in Vasterbotten, further research is needed to identify other risk
      factors besides job strain and its components that would reduce the socioeconomic
      gradient in CVD mortality. 

PMID- 25047711
TI  - Results from using a new dyadic-dependence model to analyze sociocentric
      physician networks.
AB  - Professional physician networks can potentially influence clinical practices and
      quality of care. With the current focus on coordinated care, discerning
      influences of naturally occurring clusters and other forms of dependence among
      physicians' relationships based on their attributes and care patterns is an
      important area of research. In this paper, two directed physician networks: a
      physician influential conversation network (N = 33) and a physician network
      obtained from patient visit data (N = 135) are analyzed using a new model that
      accounts for effect modification of the within-dyad effect of reciprocity and
      inter-dyad effects involving three (or more) actors. The results from this model
      include more nuanced effects involving reciprocity and triadic dependence than
      under incumbent models and more flexible control for these effects in the
      extraction of other network phenomena, including the relationship between
      similarity of individuals' attributes (e.g., same-gender, same residency
      location) and tie-status. In both cases we find extensive evidence of clustering
      and triadic dependence that if not accounted for confounds the effect of
      reciprocity and attribute homophily. Findings from our analysis suggest
      alternative conclusions to those from incumbent models. 

PMID- 25047712
TI  - Structural and functional analysis of the anti-malarial drug target prolyl-tRNA
      synthetase.
AB  - Aminoacyl-tRNA synthetases (aaRSs) drive protein translation in cells and hence
      these are essential enzymes across life. Inhibition of these enzymes can halt
      growth of an organism by stalling protein translation. Therefore, small molecule
      targeting of aaRS active sites is an attractive avenue from the perspective of
      developing anti-infectives. Febrifugine and its derivatives like halofuginone
      (HF) are known to inhibit prolyl-tRNA synthetase of malaria parasite Plasmodium
      falciparum. Here, we present functional and crystallographic data on P.
      falciparum prolyl-tRNA synthetase (PfPRS). Using immunofluorescence data, we show
      that PfPRS is exclusively resident in the parasite cytoplasm within asexual blood
      stage parasites. The inhibitor HF interacts strongly with PfPRS in a non
      competitive binding mode in presence or absence of ATP analog. Intriguingly, the
      two monomers that constitute dimeric PfPRS display significantly different
      conformations in their active site regions. The structural analyses presented
      here provide a framework for development of febrifugine derivatives that can seed
      development of new anti-malarials. 

PMID- 25047713
TI  - Career readiness in adult survivors of childhood cancer: a report from the St.
      Jude Lifetime Cohort Study.
AB  - PURPOSE: Adult survivors of childhood cancer experience difficulties in obtaining
      and maintaining employment. Employment-related challenges are associated with
      treatment-related health conditions and may also be related to vocational factors
      such as career readiness, skill acquisition, and work experience. Unfortunately,
      little is known about how treatment-, health-, and vocational-related factors
      interact to impact career development among childhood cancer survivors. METHODS:
      Three hundred eighty-five adult survivors of childhood cancer (42.1% male, median
      age 38 years (21-62)), participating in the St. Jude Lifetime Cohort Study,
      completed a work experiences survey that included measures of career readiness
      and vocational identity. Logistic regression was used to compare characteristics
      of survivors in the low career readiness category to those in the medium or high
      career readiness category, and structural equation modeling (SEM) was utilized to
      evaluate associations between career readiness, vocational identity, treatment
      intensity, and physical/emotional health. RESULTS: Low career readiness was
      prevalent in 17.4% of survivors. Univariate analysis did not identify any
      significant associations between cancer treatment-related factors and career
      readiness. Unemployed survivors (odds ratio (OR) 2.3, 95% confidence interval
      (CI) 1.2-4.5), those who were not college graduates (OR 3.0, 95% CI 1.6-5.6), and
      those who had no personal income (OR 5.9, 95% CI 1.7-30.9) were at increased risk
      of low career readiness. SEM indicated that associations between treatment
      intensity, physical health, age at diagnosis, and career readiness were mediated
      by emotional health and vocational identity. Sixty-three, 35, and 10% of the
      variance in career readiness, vocational identity, and emotional health,
      respectively, were explained by this theoretical model. CONCLUSIONS: The results
      of this study indicate that individuals who reported low levels of career
      readiness were more likely to be unemployed and earn less than US$40,000 per year
      and were less likely to graduate from high school. The final structural model
      indicates that vocational identity and emotional health accounted for the
      indirect effect of treatment intensity, age at diagnosis, and physical health on
      career readiness. IMPLICATIONS FOR CANCER SURVIVORS: Addressing career readiness
      may be important to improve employment outcomes for adult survivors of childhood
      cancer.

PMID- 25047714
TI  - Hunter-gatherer inter-band interaction rates: implications for cumulative
      culture.
AB  - Our species exhibits spectacular success due to cumulative culture. While
      cognitive evolution of social learning mechanisms may be partially responsible
      for adaptive human culture, features of early human social structure may also
      play a role by increasing the number potential models from which to learn
      innovations. We present interview data on interactions between same-sex adult
      dyads of Ache and Hadza hunter-gatherers living in multiple distinct residential
      bands (20 Ache bands; 42 Hadza bands; 1201 dyads) throughout a tribal home range.
      Results show high probabilities (5%-29% per year) of cultural and cooperative
      interactions between randomly chosen adults. Multiple regression suggests that
      ritual relationships increase interaction rates more than kinship, and that
      affinal kin interact more often than dyads with no relationship. These may be
      important features of human sociality. Finally, yearly interaction rates along
      with survival data allow us to estimate expected lifetime partners for a variety
      of social activities, and compare those to chimpanzees. Hadza and Ache men are
      estimated to observe over 300 men making tools in a lifetime, whereas male
      chimpanzees interact with only about 20 other males in a lifetime. High
      intergroup interaction rates in ancestral humans may have promoted the evolution
      of cumulative culture. 

PMID- 25047715
TI  - Cell proliferation in cubozoan jellyfish Tripedalia cystophora and Alatina
      moseri.
AB  - Cubozoans (box jellyfish) undergo remarkable body reorganization throughout their
      life cycle when, first, they metamorphose from swimming larvae to sessile polyps,
      and second, through the metamorphosis from sessile polyps to free swimming
      medusae. In the latter they develop complex structures like the central nervous
      system (CNS) and visual organs. In the present study several aspects of cell
      proliferation at different stages of the life cycle of the box jellyfish
      Tripedalia cystophora and Alatina moseri have been examined through in vivo
      labeling of cells in the synthetic phase (S phase) of the cell cycle.
      Proliferation zones were found in metamorphosing polyps, as well as in juvenile
      medusae, where both the rhopalia and pedalia have enhanced rates of
      proliferation. The results also indicate a rather fast cell turnover in the
      rhopalia including the rhopalial nervous system (RNS). Moreover, T. cystophora
      showed diurnal pattern of cell proliferation in certain body parts of the medusa,
      with higher proliferation rates at nighttime. This is true for two areas in close
      connection with the CNS: the stalk base and the rhopalia. 

PMID- 25047716
TI  - Drebrin inhibits cofilin-induced severing of F-actin.
AB  - Molecular cross-talk between neuronal drebrin A and cofilin is believed to be a
      part of the activity-dependent cytoskeleton-modulating pathway in dendritic
      spines. Impairments in this pathway are implicated also in synaptic dysfunction
      in Alzheimer's disease, Down syndrome, epilepsy, and normal aging. However, up to
      now the molecular interplay between cofilin and drebrin has not been elucidated.
      TIRF microscopy and solution experiments revealed that full length drebrin A or
      its actin binding core (Drb1-300) inhibits, but do not abolish cofilin-induced
      severing of actin filaments. Cosedimentation experiments showed that F-actin can
      be fully occupied with combination of these two proteins. The dependence of
      cofilin binding on fractional saturation of actin filaments with drebrin suggests
      direct competition between these two proteins for F-actin binding. This implies
      that cofilin and drebrin can either overcome or reverse the allosteric changes in
      F-actin induced by the competitor's binding. The ability of cofilin to displace
      drebrin from actin filaments is pH dependent and is facilitated at acidic pH
      (6.8). Pre-steady state kinetic experiments reveal that both binding and
      dissociation of drebrin to/from actin filaments is faster than that reported for
      cooperative binding of cofilin. We found, that drebrin displacement by cofilin is
      greatly inhibited when actin severing is abolished, which might be linked to the
      cooperativity of drebrin binding to actin filaments. Our results contribute to
      molecular understanding of the competitive interactions of drebrin and cofilin
      with actin filaments.

PMID- 25047717
TI  - Enterovirus71 (EV71) utilise host microRNAs to mediate host immune system
      enhancing survival during infection.
AB  - Hand, Foot and Mouth Disease (HFMD) is a self-limiting viral disease that mainly
      affects infants and children. In contrast with other HFMD causing enteroviruses,
      Enterovirus71 (EV71) has commonly been associated with severe clinical
      manifestation leading to death. Currently, due to a lack in understanding of EV71
      pathogenesis, there is no antiviral therapeutics for the treatment of HFMD
      patients. Therefore the need to better understand the mechanism of EV71
      pathogenesis is warranted. We have previously reported a human colorectal
      adenocarcinoma cell line (HT29) based model to study the pathogenesis of EV71.
      Using this system, we showed that knockdown of DGCR8, an essential cofactor for
      microRNAs biogenesis resulted in a reduction of EV71 replication. We also
      demonstrated that there are miRNAs changes during EV71 pathogenesis and EV71
      utilise host miRNAs to attenuate antiviral pathways during infection. Together,
      data from this study provide critical information on the role of miRNAs during
      EV71 infection. 

PMID- 25047718
TI  - Copper acute toxicity tests with Schizothorax o'connori Lloyd and Schizothorax
      waltoni Regan: a biomonitor of heavy metal pollution in a high altitude area?
AB  - Fingerlings of two different Schizothorax species, S. o'connori Lloyd and S.
      waltoni Regan, were exposed to copper for 264 h in a series of static toxicity
      tests. The mortality rates of these two species increased as the exposure
      concentrations increased and the exposure time was prolonged. Estimated 96 h
      median lethal concentration (LC50) values were 0.31 and 0.28 mg/L for the two
      species, respectively. These findings indicated that fingerlings of these species
      were sensitive to copper, and that both species may be suitable for use as local
      biomonitors of copper pollution in the high altitude environment. However, S.
      waltoni may be more useful in indicating the safe concentrations of copper used
      in aquaculture for therapeutic purposes. Further quantitative studies with
      measured concentrations of copper are required to verify the results observed in
      the present study.

PMID- 25047719
TI  - Catalyst-free activation of methylene chloride and alkynes by amines in a three
      component coupling reaction to synthesize propargylamines.
AB  - Propargylamines are synthesized via metal-free activation of the C-halogen bond
      of dihalomethanes and the C-H bond of terminal alkynes in a three-component
      coupling without catalyst or additional base and under mild reaction conditions.
      The dihalomethanes are used both as solvents as well as precursors for the
      methylene fragment (C1) in the final product. The scope of the reaction and the
      influence of various reaction variables has been investigated. A plausible
      reaction mechanism is proposed and the involvement of various intermediates that
      can be generated in situ in the process is discussed. The metal-free conditions
      also make this protocol environmentally benign and atom economical. 

PMID- 25047720
TI  - Evaluation of a modular scalable system for silver-ager located in assisted
      living homes in Austria--study protocol of the ModuLAAr ambient assisted living
      project.
AB  - BACKGROUND: To cope with the upcoming demographic change, economic efforts in the
      European Union are undertaken to promote activities in research and development
      of Ambient Assisted Living (AAL) solutions. As a result, a large variety of AAL
      products will be available in the next years. Only very few of these products are
      comprehensively evaluated regarding different aspects of quality of life in the
      target population. The aim of this study is to examine the effects of AAL on
      quality of life, health and technology acceptance of people at advanced age
      living in assisted living homes providing them the ModuLAAr Ambient Assisted
      Living system. METHODS/DESIGN: A treatment group of adults aged 60 years and
      older will be recruited within the participating assisted living homes. At
      baseline, the participating volunteers will report on quality of life, subjective
      health and sociodemographic conditions. After system installation, prospective
      follow-up (1, 4, 12 and 18 months) with additional reporting on technology
      acceptance and usability of the system will be conducted. Mixed methods data
      collection, linking quantitative data to interview-gathered qualitative data will
      be applied. Primary outcome measure will be the change in quality of life and
      subjective health across study duration. DISCUSSION: As there is currently very
      little evidence that AAL solutions can contribute to improved health and the
      particular dimensions of quality of life in elderly persons, there is a need to
      assess these technologies and services more carefully. This field trial seeks to
      investigate the most relevant aspects connected to advanced information and
      communication technologies and their impact on daily life of residents in
      assisted living conditions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02130102.

PMID- 25047722
TI  - Multiscale modeling of dorsoventral patterning in Drosophila.
AB  - The role of mathematical models of signaling networks is showcased by examples
      from Drosophila development. Three models of consecutive stages in dorsoventral
      patterning are presented. We begin with a compartmental model of intracellular
      reactions that generates a gradient of nuclear-localized Dorsal, exhibiting
      constant shape and dynamic amplitude. A simple thermodynamic model of equilibrium
      binding explains how a spatially uniform transcription factor, Zelda, can act in
      combination with a graded factor, Dorsal, to cooperatively regulate gene
      expression borders. Finally, we formulate a dynamic and stochastic model that
      predicts spatiotemporal patterns of Sog expression based on known patterns of its
      transcription factor, Dorsal. The future of coupling multifarious models across
      multiple temporal and spatial scales is discussed. 

PMID- 25047721
TI  - Modulation of membrane lipid composition and homeostasis in salmon hepatocytes
      exposed to hypoxia and perfluorooctane sulfonamide, given singly or in
      combination.
AB  - The relative importance of environmental hypoxia due to global climate change on
      organismal ability to adapt to chemical insult and/or mechanisms of these
      responses is not well understood. Therefore, we have studied the effects of
      combined exposure to perfluorooctane sulfonamide (PFOSA) and chemically induced
      hypoxia on membrane lipid profile and homeostasis. Primary salmon hepatocytes
      were exposed to PFOSA at 0, 25 and 50 uM singly or in combination with either
      cobalt chloride (CoCl2: 0 and 150 uM) or deferroxamine (DFO: 0 and 100 uM) for 24
      and 48 h. CoCl2 and DFO were used to induce cellular hypoxia because these two
      chemicals have been commonly used in animal experiments for this purpose and have
      been shown to increase hypoxia-inducible factor 1-alpha (HIF-1alpha) and vascular
      endothelial growth factor (VEGF) levels. Fatty acid (FA) profiles were determined
      by GC-MS, while gene expression patterns were determined by quantitative PCR.
      Hypoxic condition was confirmed with time-related increases of HIF-1alpha mRNA
      levels in CoCl2 and DFO exposed cells. In general, significant alterations of
      genes involved in lipid homeostasis were predominantly observed after 48 h
      exposure. Gene expression analysis showed that biological responses related to
      peroxisome proliferation (peroxisome proliferator-activated receptors (PPARs) and
      acyl coenzyme A (ACOX)) and FA desaturation (Delta5- and Delta6-desaturases: FAD5
      and FAD6, respectively) and elongation (FAE) were elevated slightly by single
      exposure (i.e. either PFOSA, CoCl2 or DFO exposure alone), and these responses
      were potentiated in combined exposure conditions. Principal component analysis
      (PCA) showed a clustering of peroxisome proliferation responses at transcript
      levels and FA desaturation against membrane FAs levels whose changes were
      explained by PFOSA and chemically induced hypoxia exposures. Overall, our data
      show that most of the observed responses were stronger in combined stressor
      exposure conditions, compared to individual stressor exposure. In general, our
      data show that hypoxia may, singly or in combination with PFOSA produce
      deleterious health, physiological and developmental consequences through the
      alteration of membrane lipid profile in organisms. 

PMID- 25047723
TI  - Cellulolytic and xylanolytic enzymes from thermophilic Aspergillus terreus RWY.
AB  - Thermophilic Aspergillus terreus RWY produced cellulases and xylanases in optimal
      concentrations at 45  degrees C in solid state fermentation process, though
      enzyme production was also observed at 50 and 55  degrees C. Filter paper
      cellulase (FP), endoglucanase (EG), beta-glucosidase (BGL), cellobiohydrolase
      (CBH), xylanase, beta-xylosidase, alpha-L-arabinofuranosidase and xylan esterase
      activities for A. terreus RWY at 45  degrees C in 72 h were 11.3 +/- 0.65, 103 +/
      6.4, 122.5 +/- 8.7, 10.3 +/- 0.66, 872 +/- 22.5, 22.1 +/- 0.75, 126.4 +/- 8.4
      and 907 +/- 15.5 U (g-ds)(-1) , respectively. Enzyme was optimally active at
      temperatures and pH ranging between 50-60  degrees C and 4.0-6.0, respectively.
      The half life (T1/2 ) of 270 and 240 min at 70 and 75  degrees C, respectively
      for the enzyme indicates its stability at higher temperatures. The addition of
      MnCl2 , CoCl2 , and FeCl3 significantly enhanced cellulase activity. Enzyme
      demonstrated multiplicity by having seven, one and three isoform(s) for EG, CBH
      and BGL, respectively. Significant production of functionally active consortium
      of cellulolytic and xylanolytic enzymes from A. terreus RWY makes it a potential
      candidate in bioprocessing applications. 

PMID- 25047724
TI  - Aplysin enhances temozolomide sensitivity in glioma cells by increasing miR-181
      level.
AB  - PURPOSE: Aplysin, a natural brominate compound from marine organisms, has been
      demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and
      cell cycle arrest. However, its effect on glioma is still unknown. In this study,
      we evaluated the effects of aplysin on the malignant properties of glioma cells
      and its enhancing effect on temozolomide (TMZ) action against drug-resistant
      glioma cell lines. METHODS: We employed several human glioma cell lines and
      primary glioma cells to address this issue with multidisciplinary approaches.
      RESULTS: The combined application of aplysin and TMZ significantly sensitizes
      glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis
      revealed that the abundance of miR-181, an important glioma tumor suppressors
      believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma
      cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma
      cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma
      cells. CONCLUSIONS: We found that aplysin can enhance the effect of TMZ on glioma
      cells by increasing miR-181 expression.

PMID- 25047725
TI  - Clinicopathological features of early failure of neoadjuvant chemotherapy in
      locally advanced breast cancer.
AB  - PURPOSE: Neoadjuvant chemotherapy (NAC) has been used widely in patients with
      locally advanced breast cancer (LABC). NAC has the added advantage of increasing
      breast conservation rates with similar disease-free and overall survival compared
      with adjuvant chemotherapy. A subset of patients receiving NAC experience early
      failure during the course of therapy or within a short period after breast
      surgery. There are no established predictors of early therapy failure in LABC
      patients who received NAC. This study was performed to identify patient groups
      that may not benefit from NAC. PATIENTS AND METHODS: This study was a
      retrospective single-centre study. Patients with LABC (cT2-4N0-3) were recruited
      into this analysis from January 2005 to December 2011 at the Samsung Medical
      Center. The cohort included 397 patients. The clinicopathological characteristics
      and disease courses of the patients whose disease progressed within 1 year of
      receiving neoadjuvant chemotherapy were analysed. RESULTS: Thirty-eight of the
      397 patients (9.6 %) exhibited progression within 1 year after receiving
      neoadjuvant chemotherapy. Seven of the 37 patients (18.9 %) with a known disease
      subtype, as assessed by IHC, were hormone receptor (HR)+ and HER2-. The number of
      HER2+ irrespective of HR status and triple-negative breast cancer (TNBC) patients
      was 13 (35.1 %) and 17 (45.9 %), respectively. Pathological complete remission
      was found in two patients (5.3 %, 2/38). The median overall survival period was
      20.4 months (95 % CI 17.3-23.5) in patients with early failure and 69.1 months
      (95 % CI 52.7-85.4) in the late failure group (p < 0.001), with a median follow
      up period of 35.7 months. The central nervous system (CNS) was the most common
      site of first distant metastasis (31.6 %, 12/38), and CNS failure was more common
      in patients with early failure compared with those with late failure (32.4 vs.
      3.1 %, p = 0.000). HER2 positivity or TNBC and the presence of lymphovascular
      invasion were independent predictors of early failure. CONCLUSIONS: A fraction of
      patients with LABC may not benefit from neoadjuvant chemotherapy. The results of
      our study suggest that early failure marks a high-risk group of patients who
      require innovative therapeutic approaches.

PMID- 25047726
TI  - Travel implications of emerging coronaviruses: SARS and MERS-CoV.
AB  - The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and of
      the Middle East Syndrome Cornavirus (MERS-CoV) caused widespread fear and concern
      for their potential threat to global health security. There are similarities and
      differences in the epidemiology and clinical features between these two diseases.
      The origin of SARS-COV and MERS-CoV is thought to be an animal source with
      subsequent transmission to humans. The identification of both the intermediate
      host and the exact route of transmission of MERS-CoV is crucial for the
      subsequent prevention of the introduction of the virus into the human population.
      So far MERS-CoV had resulted in a limited travel-associated human cases with no
      major events related to the Hajj. 

PMID- 25047727
TI  - Tools for travellers' diarrhoea: bring back the vaccine?

PMID- 25047728
TI  - Electrical conductivity of ice VII.
AB  - It was discovered that a peak appears near a pressure of Pc = 10 GPa in the
      electrical conductivity of ice VII as measured through impedance spectroscopy in
      a diamond anvil cell (DAC) during the process of compression from 2 GPa to 40 GPa
      at room temperature. The activation energy for the conductivity measured in the
      cooling/heating process between 278 K and 303 K reached a minimum near Pc.
      Theoretical modelling and molecular dynamics simulations suggest that the origin
      of this unique peak is the transition of the major charge carriers from the
      rotational defects to the ionic defects.

PMID- 25047729
TI  - Guidelines for rehabilitation in patients with cardiovascular disease (JCS 2012).

PMID- 25047731
TI  - Finding a cure for HIV: much work to do.

PMID- 25047730
TI  - Long-term safety of immunomodulators in pediatric inflammatory diseases.
AB  - The medical management of chronic inflammatory disorders in children, including
      mainly inflammatory bowel diseases and rheumatic diseases, has evolved
      dramatically over recent years with the advent of disease-modifying drugs such as
      immunomodulators and biological agents capable of interrupting the inflammatory
      cascade underlying these disorders. These agents are generally administered in
      patients who are refractory to conventional therapies. However, there is growing
      support that their use in the initial phases of these disorders, especially in
      pediatric patients, could interrupt and cease the inflammatory process. Thus, the
      aims of therapy have transitioned from symptomatic control to the achievement of
      deeper remission, including the healing of the inflammatory lesions combined with
      symptomatic remission. Therefore, more patients are currently receiving
      immunomodulators or biologics, frequently in addition to corticosteroids.
      Immunosuppression due to these therapies increases safety concerns, particularly
      regarding the risk of infections and malignancies. The available literature
      highlights how the combination of more than one of these therapies, especially if
      the combination includes corticosteroids, amplifies the risk of severe
      opportunistic infections. Otherwise, the infections described are mainly mild.
      Regarding malignancies, the overall risk associated with treatment appears non
      significant in pediatric populations, but an appropriate benefit/risk assessment
      is recommended prior to the introduction of aggressive treatments such as
      immunomodulants and biologics. The background cancer risk related to the disease
      itself remains an issue. Protracted follow-up programs are needed, and the
      results from international multicenter registries are awaited to better
      understand the true risk related to therapy of these pediatric populations. 

PMID- 25047733
TI  - Study on anterior and posterior approaches for spinal tuberculosis: a meta
      analysis.
AB  - BACKGROUND: Timely and appropriate surgical intervention can enhance the
      stability of spine, eliminate the compression on spinal cord and prevent the
      further development the complications that may follow. However, there is no
      optimum surgical approach that has been agreed by surgeons. OBJECTIVE: Incidence
      rate of spinal tuberculosis is still high in many developing countries. Except
      from chemotherapy, some patients require surgical treatment at certain phases of
      disease development. However, there is still not a standard operative procedure
      for spinal tuberculosis in the current research, and we studied the differences
      of anterior and posterior approach for spinal tuberculosis, to provide guidance
      for the further operative treatments. METHODS: We searched "Pubmed" (2000.1
      2014.7), "Medline" (2000.1-2014.7), "Elseveir" (2000.1-2014.7), Cochrane library
      (2008.1-2014.7), Wanfang (2000.1-2014.7), and CNKI (2000.1-2014.7) databases with
      the key words of "thoracolumbar tuberculosis", "controlled randomized trial",
      "RCT", "anterior" "posterior", and searched for randomized controlled trials for
      spinal tuberculosis. We compared the operative time, total blood loss, correction
      of Cobb angle, loss of Cobb angle at final follow-up, fusion time of allograft,
      time of total hospital stay, and the effectiveness of operative treatment between
      the anterior and posterior surgical approaches by Revman5.3 software. RESULTS:
      From 1,523 papers found, we chose eight randomized controlled trials comparing
      different surgical approaches for the treatment of spinal tuberculosis. The total
      number of patients was 754, in which 377 were treated with anterior approach and
      377 were treated with posterior approach correction of Cobb angle (P < 0.05), and
      no significant differences were found regarding operation time, loss of
      correction of Cobb angle in the last follow-up, time of total hospital stay, and
      fusion time of bone graft (P > 0.05). CONCLUSIONS: There are significant
      differences between the two operative approaches regarding the correction of Cobb
      angle, but no significant differences regarding operation time, blood loss, loss
      of Cobb angle at the last follow-up, total fusion time, and length of total stay
      in the hospital.

PMID- 25047732
TI  - Is acetabular osteoplasty always required in mixed impingement?
AB  - BACKGROUND: Mixed femoroacetabular impingement (FAI) is typically managed with
      both femoral and acetabular rim osteoplasties, but it has not been reported if
      the rim osteoplasty is always required. HYPOTHESIS/PURPOSE: We hypothesized that
      mixed FAI managed by femoral or combined femoral and acetabular osteoplasties
      will both attain satisfactory clinical results, provided intraoperative
      impingement-free functional motion is attained. METHODS: We retrospectively
      reviewed 30 hips (23 patients, mean age at surgery 24.3 years, mean follow-up
      time 1.6 years) with mixed FAI who underwent surgical dislocation of the hip and
      had femoral osteochondroplasty with rim trim (RT, n = 21) or no rim trim (NRT, n
      = 9). Physical examination results and Western Ontario and McMaster Universities
      Osteoarthritis (WOMAC) scores were evaluated. RESULTS: Mean (+/- SD) WOMAC pain
      scores improved from 6.56 (+/- 2.96) to 2.33 (+/- 3.64) in the NRT group (p =
      .002) and from 6.86 (+/- 4.15) to 3.86 (+/- 3.95) in the RT group (p = .014).
      Function improved in both groups, but the difference was significant only for the
      NRT group (p < .001). Over 50 % of patients in both groups had resolution of
      impingement sign. Internal rotation increased from 8.6 degrees  (+/- 11.8) to
      20.0 degrees  (+/- 10.4) in the NRT group (p = .043) and from 4.0 degrees  (+/-
      12.1) to 18.6 degrees  (+/- 14.0) in the RT group (p < .001). Both groups had
      increased flexion post-operatively to normal range, but the change was only
      significant for the RT group (p = .02). Both groups had insignificant decreases
      in external rotation. CONCLUSION: Satisfactory clinical outcomes were seen in
      hips with mixed impingement, regardless of whether RT was performed, provided
      impingement-free functional motion was attained and no severe cartilage damage
      was seen.

PMID- 25047734
TI  - An effective and robust method for modeling multi-furcation liver vessel by using
      Gap Border Pairing.
AB  - Shape-based 3D surface reconstructing methods for liver vessels have difficulties
      to tackle with limited contrast of medical images and the intrinsic complexity of
      multi-furcation parts. In this paper, we propose an effective and robust
      technique, called Gap Border Pairing (GBPa), to reconstruct surface of liver
      vessels with complicated multi-furcations. The proposed method starts from a tree
      like skeleton which is extracted from segmented liver vessel volumes and
      preprocessed as a number of simplified smooth branching lines. Secondly, for each
      center point of any branching line, an optimized elliptic cross-section ring
      (contour) is generated by optimizedly fitting its actual cross-section outline
      based on its tangent vector. Thirdly, a tubular surface mesh is generated for
      each branching line by weaving all of its adjacent rings. Then for every multi
      furcation part, a transitional regular mesh is effectively and regularly
      reconstructed by using GBP. An initial model is generated after reconstructing
      all multi-furcation parts. Finally, the model is refined by using just one time
      subdivision and its topologies can be re-maintained by grouping its facets
      according to the skeleton, providing high-level editability. Our method can be
      automatically implemented in parallel if the segmented vessel volume and
      corresponding skeletons are provided. The experimental results show that GBP
      model is accurate enough in terms of the boundary deviations between segmented
      volume and the model. 

PMID- 25047735
TI  - Current and advancing treatments for pulmonary arterial hypertension in
      childhood.
AB  - Pulmonary arterial hypertension (PAH) is a severe and progressive intrinsic
      disease of the precapillary lung vasculature. Since the introduction of PAH
      targeted drugs, survival of PAH patients seems to have improved. Randomized
      controlled trials have led to evidence-based guidelines to direct treatment in
      adults. However, since disease characteristics differ between adults and
      children, it is hazardous to simply extrapolate these guidelines to children.
      Moreover, pediatric data on treatment strategies and how to assess treatment
      response remain virtually absent. Optimal treatment strategies are highly needed
      to guide therapy and improve survival in children with PAH. This review provides
      an overview of currently available treatments for PAH and the limited efficacy
      and safety data in children (with the exclusion of perinatal pulmonary vascular
      diseases, as persistent pulmonary hypertension of the newborn). We also discuss
      potential treatment goals and how the available data can be translated into
      treatment strategies in pediatric PAH. 

PMID- 25047736
TI  - Delphinidin-3-glucoside protects human umbilical vein endothelial cells against
      oxidized low-density lipoprotein-induced injury by autophagy upregulation via the
      AMPK/SIRT1 signaling pathway.
AB  - SCOPE: Oxidized LDL (oxLDL) induced vascular endothelial cell injury is a key
      event in the pathogenesis of atherosclerosis (AS). In our previous studies, we
      showed that delphinidin-3-glucoside (Dp), a natural anthocyanin, attenuated oxLDL
      induced injury in human umbilical vein endothelial cells (HUVECs), indicating its
      potential role in preventing AS. However, the involved mechanism is not fully
      understood. METHODS AND RESULTS: Via methyl thiazolyl tetrazolium and flow
      cytometry assay, we found that Dp-attenuated oxLDL-induced cell viability
      decrease and apoptosis in HUVECs. Depending on confocal microscopy, transmission
      electron microscopy, and Western blot assay, we found that Dp-induced autophagy
      in HUVECs, whereas suppression of autophagy significantly abolished the
      protective role of Dp against oxLDL-induced endothelial cell injury. Furthermore,
      Dp upregulated sirtuin 1 (SIRT1) expression and SIRT1 knockdown notably
      suppressed Dp-induced autophagy in HUVECs. Dp also increased the expression of
      phosphorylated adenosine monophosphate-activated protein kinase, while adenosine
      monophosphate-activated protein kinase (AMPK) knockdown remarkably abolished Dp
      induced SIRT1 expression and subsequent autophagy. CONCLUSION: Our data suggested
      that Dp protected HUVECs against oxLDL-induced injury by inducing autophagy via
      the adenosine monophosphate-activated protein kinase/SIRT1 signaling pathway.
      This new finding might shed light to the prevention and therapy of AS.

PMID- 25047737
TI  - Understanding and achieving person-centred care: the nurse perspective.
AB  - AIMS AND OBJECTIVES: To present findings from the first stage of an exploratory
      study investigating nurses' understanding and facilitation of person-centred care
      within an acute medical ward. BACKGROUND: The term 'person-centred care' is used
      frequently in healthcare policy and practice. However, the ways in which the
      concept is translated into everyday nursing care continue to present a challenge.
      Person-centred care has been explored extensively within the care of older
      people, people with dementia and people with a learning disability. Little
      empirical research has been conducted in acute ward settings. This study starts
      to address that gap. DESIGN: The study used an action research approach. METHODS:
      Individual semi-structured interviews were conducted with a purposeful sample of
      14 nurses. Framework analysis was used to analyse the data. RESULTS: Nurses had a
      clear understanding of person-centred care in the context of their work. They
      acknowledged the importance of relationships, personal qualities of staff and
      respecting the principles of person-centred care as they strived to provide safe,
      high-quality person-centred care. CONCLUSION: The examples of care given by the
      nurses in this study resonate with the 'six Cs' emphasised by the Chief Nursing
      Officer for England in 2012, acknowledge the motivation of nurses to provide
      person-centred care and will contribute to the ongoing debate about nursing
      practice. RELEVANCE TO CLINICAL PRACTICE: In the light of recent criticisms of
      nursing and the implied erosion of public confidence in the provision of high
      quality health care, it is important to recognise good practice and use the
      findings as a foundation for further and sustained development in providing
      person-centred care.

PMID- 25047739
TI  - The PsbS protein plays important roles in photosystem II supercomplex remodeling
      under elevated light conditions.
AB  - Leaves from three different Arabidopsis lines with different expression levels of
      PsbS protein showed different levels of non-photochemical quenching. The PsbS
      deficient plant npq4 showed remarkable reduction of electron transport rate,
      while the other two lines with a moderate amount (wild type) or an overexpression
      of PsbS (L17) presented unchanged electron transport rates under the same range
      of high light intensities. Biochemical investigation revealed that the plant with
      the highest PsbS content (L17) sustained the highest level of stable PSII-LHCII
      supercomplex structure, and displayed the smallest fluorescence quenching in the
      thylakoid membranes, the most efficient linear electron transport and the
      smallest cyclic electron transport. Based on these observations, it is proposed
      that the remodeling of PSII-LHCII supercomplexes affected by PsbS plays important
      roles in regulating the energy balance in thylakoid membrane and in ensuring the
      sophisticated coordination between energy excitation and dissipation. 

PMID- 25047738
TI  - Circulating mouse Flk1+/c-Kit+/CD45- cells function as endothelial progenitors
      cells (EPCs) and stimulate the growth of human tumor xenografts.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) have been demonstrated to have
      stem-cell like as well as mature endothelial functions. However, controversy
      remains as to their origins, immunophenotypic markings, and contribution to the
      tumor vascular network and tumor survival. METHODS: Flow cytometric analysis and
      sorting was used to isolate Flk-1+/c-Kit+/CD45- cells. Matrigel and
      methycellulose assays, flow cytometry, and gene array analyses were performed to
      characterize several murine EPC cell populations. Human tumor xenografts were
      used to evaluate the impact of EPCs on tumor growth and vascular development.
      RESULTS: Flk-1+/c-Kit+/CD45- cells were present at low levels in most murine
      organs with the highest levels in adipose, aorta/vena cava, and lung tissues. Flk
      1+/c-Kit+/CD45- cells demonstrated stem cell qualities through colony forming
      assays and mature endothelial function by expression of CD31, uptake of acLDL,
      and vascular structure formation in matrigel. High passage EPCs grown in vitro
      became more differentiated and lost stem-cell markers. EPCs were found to have
      hemangioblastic properties as demonstrated by the ability to rescue mice given
      whole body radiation. Systemic injection of EPCs increased the growth of human
      xenograft tumors and vessel density. CONCLUSIONS: Flk-1+/C-Kit+/CD45- cells
      function as endothelial progenitor cells. EPCs are resident in most murine tissue
      types and localize to human tumor xenografts. Furthermore, the EPC population
      demonstrates stem-cell and mature endothelial functions and promoted the growth
      of tumors through enhanced vascular network formation. Given the involvement of
      EPCs in tumor development, this unique host-derived population may be an
      additional target to consider for anti-neoplastic therapy.

PMID- 25047740
TI  - Glenohumeral joint cartilage contact in the healthy adult during scapular plane
      elevation depression with external humeral rotation.
AB  - The shoulder (glenohumeral) joint has the greatest range of motion of all human
      joints; as a result, it is particularly vulnerable to dislocation and injury. The
      ability to non-invasively quantify in-vivo articular cartilage contact patterns
      of joints has been and remains a difficult biomechanics problem. As a result,
      little is known about normal in-vivo glenohumeral joint contact patterns or the
      consequences that surgery has on altering them. In addition, the effect of
      quantifying glenohumeral joint contact patterns by means of proximity mapping,
      both with and without cartilage data, is unknown. Therefore, the objectives of
      this study are to (1) describe a technique for quantifying in-vivo glenohumeral
      joint contact patterns during dynamic shoulder motion, (2) quantify normal
      glenohumeral joint contact patterns in the young healthy adult during scapular
      plane elevation depression with external humeral rotation, and (3) compare
      glenohumeral joint contact patterns determined both with and without articular
      cartilage data. Our results show that the inclusion of articular cartilage data
      when quantifying in-vivo glenohumeral joint contact patterns has significant
      effects on the anterior-posterior contact centroid location, the superior
      inferior contact centroid range of travel, and the total contact path length. As
      a result, our technique offers an advantage over glenohumeral joint contact
      pattern measurement techniques that neglect articular cartilage data. Likewise,
      this technique may be more sensitive than traditional 6-Degree-of-Freedom (6-DOF)
      joint kinematics for the assessment of overall glenohumeral joint health. Lastly,
      for the shoulder motion tested, we found that glenohumeral joint contact was
      located on the anterior-inferior glenoid surface. 

PMID- 25047741
TI  - Body segment inertial parameters and low back load in individuals with central
      adiposity.
AB  - There is a paucity of information regarding the impact of central adiposity on
      the inertial characteristics of body segments. Deriving low back loads during
      lifting requires accurate estimate of inertial parameters. The purpose was to
      determine the body segment inertial parameters of people with central adiposity
      using a photogrammetric technique, and then to evaluate the impact on lumbar
      spine loading. Five participants with central adiposity (waist:hip ratio>0.9,
      waist circumference>102 cm) were compared to a normal BMI group. A 3D wireframe
      model of the surface topography was constructed, partitioned into 8 body segments
      and then body segment inertial parameters were calculated using volumetric
      integration assuming uniform segment densities for the segments. Central
      adiposity dependent increases in body segment parameters ranged from 12 to 400%,
      varying across segments (greatest for trunk) and parameters. The increase in mass
      distribution to the trunk was accompanied by an anterior and inferior shift of
      the centre of mass. A proximal shift in centre of mass was detected for the
      extremities, along with a reduction in mass distribution to the lower extremity.
      L5/S1 torques (392 vs 263 Nm) and compressive forces (5918 vs 3986 N) were
      substantially elevated in comparison to the normal BMI group, as well as in
      comparison to torques and forces predicted using published BSIP equations.
      Central adiposity resulted in substantial but non-uniform increases in inertial
      parameters resulting in task specific increases in torque and compressive loads
      arising from different inertial and physical components.

PMID- 25047742
TI  - Antioxidants and redox processes in health - bilateral meeting Brazil-Japan.

PMID- 25047743
TI  - Decreased expression of glutathione S-transferase pi correlates with poorly
      differentiated grade in patients with oral squamous cell carcinoma.
AB  - BACKGROUND: Glutathione S transferase pi (GSTP1) is a member of phase II
      detoxification enzymes as a major regulator of cell signaling in response to
      stress, hypoxia, growth factors, and other stimuli. The clinical role of GSTP1 in
      cancer is still unclear. The aim of this study was to investigate the serum GSTP1
      level in patients with oral squamous cell carcinoma (OSCC) and the GSTP1
      expression in tissue samples from patients with OSCC and OSCC lines. METHODS: One
      hundred and sixty-six patients with OSCC and 120 normal persons were used to
      screen potential serum peptide biomarkers using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Serum
      GSTP1 concentration was detected in 18 patients with OSCC and 18 normal persons
      using ELISA. Immunohistochemistry was used to detect GSTP1 expression in tissue
      samples from twenty-eight OSCC patients. Western blot and real-time PCR were used
      to detect GSTP1 expression in nine OSCC lines. RESULTS: Decreased GSTP1
      concentration was found in the patients with OSCC compared with the normal
      persons by MALDI-TOF-MS, which was then confirmed by ELISA (P = 0.019). Decreased
      GSTP1 mRNA level and protein expression were also found in the OSCC lines.
      Decreased GSTP1 expression was found correlating with pathological
      differentiation grade in the tissue samples from OSCC patients, a lower GSTP1
      expression indicating a poorer pathological differentiation grade (P = 0.041).
      CONCLUSIONS: These results suggest that decreased GSTP1 expression in patients
      with OSCC and a lower GSTP1 expression indicating a poorer pathological
      differentiation grade in OSCC tissue samples.

PMID- 25047744
TI  - Longer hospital stay is associated with higher rates of tuberculosis-related
      morbidity and mortality within 12 months after discharge in a referral hospital
      in Sub-Saharan Africa.
AB  - BACKGROUND: Nosocomial transmission of pulmonary tuberculosis (PTB) is a problem
      in resource-limited settings. However, the degree of TB exposure and the
      intermediate- and long-term morbidity and mortality of hospital-associated TB is
      unclear. In this study we determined: 1) the nature, patterns and intensity of TB
      exposure occurring in the context of current TB cohorting practices in medical
      centre with a high prevalence of TB and HIV; 2) the one-year TB incidence after
      discharge; and 3) one-year TB-related mortality after hospital discharge.
      METHODS: Factors leading to nosocomial TB exposure were collected daily over a 3
      month period. Patients were followed for 1-year after discharge. TB incidence and
      mortality were calculated and logistic regression was used to determine the
      factors associated with TB incidence and mortality during follow up. RESULTS:
      1,094 patients were admitted to the medical wards between May 01 and July 31,
      2010. HIV was confirmed in 690/1,094 (63.1%) of them. A total of 215/1,094
      (19.7%) patients were diagnosed with PTB and 178/1,094 (16.3%) patients died
      during the course of their hospitalization; 12/178 (6.7%) patients died from TB
      related complications. Of the 896 (83.7%) discharged patients, 41 (4.6%)
      [corrected] were diagnosed with TB during the year of follow up. Overall, 123/896
      (14%) patients died during the follow up period, of whom 26/123 (21%) died from
      TB. [corrected] One-year TB incidence rate and TB-associated mortality were
      associated with the number of days that the patient remained hospitalized, the
      number of days spent in the cohorting bay (regardless of whether the patient was
      eventually diagnosed with TB or not), and the number and proximity to TB index
      cases. There was no difference in the performance of each of these 3 measurements
      of nosocomial TB exposure for the prediction of one-year TB incidence.
      CONCLUSION: Substantial TB exposure, particularly among HIV-infected patients,
      occurs in nosocomial settings despite implementation of cohorting measures.
      Nosocomial TB exposure is strongly associated with one-year TB incidence and TB
      related mortality. Further studies are needed to identify strategies to reduce
      such exposure among susceptible patients.

PMID- 25047745
TI  - Oxytocin attenuates neural reactivity to masked threat cues from the eyes.
AB  - The neuropeptide oxytocin has recently been shown to modulate covert attention
      shifts to emotional face cues and to improve discrimination of masked facial
      emotions. These results suggest that oxytocin modulates facial emotion processing
      at early perceptual stages prior to full evaluation of the emotional expression.
      Here, we used functional magnetic resonance imaging to examine whether oxytocin
      alters neural responses to backwardly masked angry and happy faces while
      controlling for attention to the eye vs the mouth region. Intranasal oxytocin
      administration reduced amygdala reactivity to masked emotions when attending to
      salient facial features, ie, the eyes of angry faces and the mouth of happy
      faces. In addition, oxytocin decreased neural responses within the fusiform gyrus
      and brain stem areas, as well as functional coupling between the amygdala and the
      fusiform gyrus specifically for threat cues from the eyes. Effects of oxytocin on
      brain activity were not attributable to differences in behavioral performance, as
      oxytocin had no impact on mere emotion detection. Our results suggest that
      oxytocin attenuates neural correlates of early arousal by threat signals from the
      eye region. As reduced threat sensitivity may increase the likelihood of engaging
      in social interactions, our findings may have important implications for clinical
      states of social anxiety. 

PMID- 25047746
TI  - Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive
      impairment in a transgenic mouse model of Alzheimer's disease.
AB  - Triggering receptor expressed on myeloid cells 2 (TREM2) gene is a recently
      identified susceptibility gene for Alzheimer's disease (AD), as its low-frequency
      variants increase the risk of this disease with an odds ratio similar to that of
      an APOE E4 allele. To date, the expression and biologic functions of TREM2 under
      AD context remain largely unknown. Using APPswe/PS1dE9 mice, a transgenic model
      of AD, we showed that TREM2 was upregulated in microglia during disease
      progression. For the first time, we provided in vitro and in vivo evidence that
      this upregulation was attributed to the increased amyloid-beta (Abeta)(1-42)
      levels in the brain. By knockdown and overexpression of TREM2 in cultured primary
      microglia, we revealed that TREM2 modulated microglial functions under AD
      context, as it facilitated Abeta(1-42) phagocytosis and inhibited Abeta(1-42)
      triggered proinflammatory responses. Meanwhile, this modulation was dependent on
      DAP12, the adapter protein of TREM2. More importantly, overexpression of TREM2 in
      the brain of APPswe/PS1dE9 mice markedly ameliorated AD-related neuropathology
      including Abeta deposition, neuroinflammation, and neuronal and synaptic losses,
      which was accompanied by an improvement in spatial cognitive functions. Taken
      together, our data suggest that the upregulation of TREM2 serves as a
      compensatory response to Abeta(1-42) and subsequently protects against AD
      progression by modulation of microglia functions. These findings provide insights
      into the role of TREM2 in AD pathogenesis, and highlight TREM2 as a potential
      therapeutic target for this disease.

PMID- 25047747
TI  - A prognostic factor index for overall survival in patients receiving first-line
      chemotherapy for HER2-negative advanced breast cancer: an analysis of the ATHENA
      trial.
AB  - BACKGROUND: Evidence-based definitions of 'poor-prognosis' or 'aggressive'
      advanced breast cancer are lacking. PATIENTS AND METHODS: We developed a
      prognostic factor index using data from 2203 patients treated with first-line
      chemotherapy plus bevacizumab for HER2-negative advanced breast cancer. RESULTS:
      The risk factors most closely associated with worse OS were: disease-free
      interval <=24 months; liver metastases or >=3 involved organ sites; prior
      anthracycline and/or taxane therapy; triple-negative breast cancer (TNBC); and
      performance status 2 or prior analgesic/corticosteroid treatment. Risk of death
      was increased threefold in patients with >=3 versus <=1 risk factors (hazard
      ratio 3.0 [95% CI 2.6-3.4; p < 0.001]; median 16.0 vs 38.8 months, respectively).
      CONCLUSIONS: This prognostic index may enable identification of patients with a
      poorer prognosis in whom more intensive systemic regimens may be appropriate. The
      index may also be considered in designing new trials, although it requires
      validation in other datasets before extrapolation to non-bevacizumab-containing
      therapy. ClinicalTrials.gov identifier: NCT00448591.

PMID- 25047748
TI  - Influence of Carbon and Microbial Community Priming on the Attenuation of Uranium
      in a Contaminated Floodplain Aquifer.
AB  - The capacity for subsurface sediments to sequester radionuclide contaminants,
      such as uranium (U), and retain them after bioremediation efforts are completed
      is critical to the long-term stewardship of re-mediated sites. In U
      bioremediation strategies, carbon amendment stimulates bioreduction of U(VI) to
      U(IV), immobilizing it within the sediments. Sediments enriched in natural
      organic matter are naturally capable of sequestering significant U, but may serve
      as sources to the aquifer, contributing to plume persistence. Two types of
      organic-rich sediments were compared to better understand U release mechanisms.
      Sediments that were artificially primed for U removal were retrieved from an area
      previously biostimulated while detrital-rich sediments were collected from a
      location never subject to amendment. Batch incubations demonstrated that primed
      sediments rapidly removed uranium from the groundwater, whereas naturally reduced
      sediments released a sizeable portion of U before U(VI)-reduction commenced.
      Column experiments confirmed that U release persisted for 65 pore volumes in
      naturally reduced sediments, demonstrating their sink-source behavior. Acetate
      addition to primed sediments shifted the microbial community from sulfate
      reducing bacteria within Desulfobacteraceae to the iron-reducing Geobacteraceae
      and Firmicutes, associated with efficient U(VI) removal and retention,
      respectively. In contrast, Geobacteraceae communities in naturally reduced
      sediments were replaced by sequences with similarity to Pseudomonas spp. during U
      release, while U(VI) removal only occurred with enrichment of Firmicutes. These
      investigations stress the importance of characterizing zones with heterogeneous
      carbon pools at U-contaminated sites prior to the determination of a remedial
      strategy to identify areas, which may contribute to long-term sourcing of the
      contaminants. 

PMID- 25047749
TI  - Biochemical and molecular characteristics of patients with organic acidaemias and
      urea cycle disorders identified through newborn screening.
AB  - BACKGROUND: In recent years it has become clear that newborn screening (NBS)
      programmes using tandem mass spectrometry identify "patients" with "classical"
      inborn errors of metabolism who are asymptomatic. This observation raises issues
      regarding medicalization of "non-diseases," potentially unnecessary treatment and
      unnecessary anxiety to parents. AIMS: This study aims to identify possible
      markers that may assist in predicting the need for treatment of infants with
      "classical" organic acidaemias (OA) and urea cycle disorders (UCD) diagnosed
      through NBS. METHODS: Medical records of all patients with classical OA and UCD
      detected through the Victorian NBS programme from February 2002 to January 2014,
      or diagnosed clinically between 1990 and January 2002 were retrospectively
      reviewed. RESULTS: Neonatal presentation did not always predict the need for on
      going strict treatment. Blood concentrations of amino acids and acyl-carnitines
      and the changes thereof in follow-up samples correlated with severity in
      citrullinaemia-I, possibly isovaleric acidaemia but not in argininosuccinic
      aciduria or propionic acidaemia. Some specific mutations correlate with
      "attenuated" citrullinaemia-I. Gender may affect clinical outcome in propionic
      acidaemia. CONCLUSIONS: Changes in blood concentration of certain metabolites
      (amino acids, acyl-carnitines) in the first weeks of life may be predictive of
      the need for treatment in some disorders but not in others. Mutation analysis may
      be predictive in some disorders but whether or not this should be considered as
      second-tier testing in NBS should be discussed separately.

PMID- 25047751
TI  - Glycan-dependent viral infection in infants and the role of human milk
      oligosaccharides.
AB  - Glycan interactions play a crucial role in the infection of rotavirus (RV),
      norovirus (NV) and human immunodeficiency virus (HIV) as they facilitate viral
      attachment to the host receptor cell. A number of cell surface glycan epitopes
      involved in this process have been identified, including human blood group
      antigens (HBGAs). These antigens are also found on human milk oligosaccharides
      (HMO), an abundant and structurally diverse component in human milk. Breast-fed
      infants seem to have a reduced risk of acquiring RV, NV and HIV infection,
      suggesting a potential effector function of milk oligosaccharides in viral
      pathogenesis. However, the underlying mechanisms of HMO in viral protection and
      the identification of individual, structurally distinct effective HMO, needs
      further elucidation. 

PMID- 25047750
TI  - Peroxisome proliferator-activated receptor gamma coactivator 1alpha and FoxO3A
      mediate chondroprotection by AMP-activated protein kinase.
AB  - OBJECTIVE: AMP-activated protein kinase (AMPK) inhibits chondrocyte procatabolic
      responses to inflammation and biomechanical injury. This study was undertaken to
      test the hypothesis that peroxisome proliferator-activated receptor gamma
      coactivator 1alpha (PGC-1alpha) and FoxO3A, 2 major AMPK downstream targets,
      mediate the chondroprotective effect of AMPK activation. METHODS: We assessed the
      activity of AMPKalpha (threonine 172 phosphorylation) and the expression of PGC
      1alpha and FoxO3A in human chondrocytes and AMPKalpha1- or AMPKalpha2-knockout
      mouse chondrocytes by Western blotting, and in mouse knee cartilage by
      immunohistochemistry. We also knocked down or overexpressed PGC-1alpha and FoxO3A
      by small interfering RNA or plasmid DNA transfection, respectively. We assessed
      mitochondrial superoxide generation using MitoSOX Red. RESULTS: Expression of PGC
      1alpha and FoxO3A was enhanced by pharmacologic AMPK activator A-769662 but
      impaired in AMPKalpha1(-/-) or AMPKalpha2(-/-) mouse chondrocytes. Reduced
      expression of PGC-1alpha and FoxO3A was observed in mouse knee instability
      induced osteoarthritis (OA) cartilage and in aged C57BL/6 mouse knee cartilage.
      Knockdown of PGC-1alpha and FoxO3A enhanced, but limited the ability of A-769662
      to inhibit, phosphorylation of p65 NF-kappaB (Ser(536) ) and procatabolic
      responses induced by inflammatory cytokines. Forced expression of PGC-1alpha and
      FoxO3A induced increased expression of superoxide dismutase 2 (SOD2) and
      catalase, but A-769662 failed to increase the expression of SOD2 and catalase in
      either PGC-1alpha- or FoxO3A-knockdown chondrocytes. Last, menadione-induced
      superoxide generation was inhibited by AMPK pharmacologic activators and by
      overexpression of PGC-1alpha or FoxO3A. CONCLUSION: PGC-1alpha and FoxO3A limit
      oxidative stress and at least partially mediate the capacity of AMPK activity to
      block procatabolic responses in chondrocytes, and therefore have the potential to
      inhibit the progression of cartilage damage in OA.

PMID- 25047753
TI  - Dynamic probabilistic threshold networks to infer signaling pathways from time
      course perturbation data.
AB  - BACKGROUND: Network inference deals with the reconstruction of molecular networks
      from experimental data. Given N molecular species, the challenge is to find the
      underlying network. Due to data limitations, this typically is an ill-posed
      problem, and requires the integration of prior biological knowledge or strong
      regularization. We here focus on the situation when time-resolved measurements of
      a system's response after systematic perturbations are available. RESULTS: We
      present a novel method to infer signaling networks from time-course perturbation
      data. We utilize dynamic Bayesian networks with probabilistic Boolean threshold
      functions to describe protein activation. The model posterior distribution is
      analyzed using evolutionary MCMC sampling and subsequent clustering, resulting in
      probability distributions over alternative networks. We evaluate our method on
      simulated data, and study its performance with respect to data set size and
      levels of noise. We then use our method to study EGF-mediated signaling in the
      ERBB pathway. CONCLUSIONS: Dynamic Probabilistic Threshold Networks is a new
      method to infer signaling networks from time-series perturbation data. It
      exploits the dynamic response of a system after external perturbation for network
      reconstruction. On simulated data, we show that the approach outperforms current
      state of the art methods. On the ERBB data, our approach recovers a significant
      fraction of the known interactions, and predicts novel mechanisms in the ERBB
      pathway.

PMID- 25047752
TI  - Parvovirus glycan interactions.
AB  - Members of the Parvoviridae utilize glycan receptors for cellular attachment and
      subsequent interactions determine transduction efficiency or pathogenic outcome.
      This review focuses on the identity of the glycan receptors utilized, their
      capsid binding footprints, and a discussion of the overlap of these sites with
      tropism, transduction, and pathogenicity determinants. Despite high sequence
      diversity between the different genera, most parvoviruses bind to negatively
      charged glycans, such as sialic acid and heparan sulfate, abundant on cell
      surface membranes. The capsid structure of these viruses exhibit high structural
      homology enabling common regions to be utilized for glycan binding. At the same
      time the sequence diversity at the common footprints allows for binding of
      different glycans or differential binding of the same glycan. 

PMID- 25047754
TI  - Cost-effectiveness analysis of HLA-B5801 genotyping in the treatment of gout
      patients with chronic renal insufficiency in Korea.
AB  - OBJECTIVE: Allopurinol-induced severe cutaneous adverse reactions (SCARs) are
      relatively rare but cause high rates of morbidity and mortality. Studies have
      shown that the HLA-B5801 allele and renal impairment are strongly associated with
      SCARs. Recent American College of Rheumatology guidelines recommend that, prior
      to treatment with allopurinol, the HLA-B5801 genotype of gout patients at high
      risk for SCARs, including Korean patients with chronic renal insufficiency,
      should be determined. However, whether such genotyping is cost-effective is
      unknown. This study evaluated the cost-effectiveness of HLA-B5801 genotyping for
      the treatment of gout in patients with chronic renal insufficiency in Korea.
      METHODS: A decision analytical model over a time period of 12 months was employed
      to compare the cost and outcomes of treatment informed by HLA-B5801 genotyping
      with that of a conventional treatment strategy using a hypothetical cohort of
      gout patients with chronic renal insufficiency. Direct medical costs were
      obtained from real patients with SCARs from 2 tertiary hospitals. Outcomes were
      measured as a total expected cost and an incremental cost-effectiveness ratio.
      RESULTS: In the base model, the total expected cost and probability of
      continuation of gout treatment without SCARs for the conventional and HLA-B5801
      screening strategies were $1,193 and 97.8% and $1,055 and 100%, respectively. The
      results were robust according to sensitivity analyses. CONCLUSION: Our model
      suggests that gout treatment informed by HLA-B5801 genotyping is less costly and
      more effective than treatment without genotyping, and HLA-B5801 genotyping could
      considerably reduce the occurrence of allopurinol-induced SCARs and related
      deaths.

PMID- 25047755
TI  - Evaluation of two point-of-care ethylene glycol tests for dogs.
AB  - OBJECTIVE: To evaluate 2 point-of-care ethylene glycol (EG) tests in dogs.
      DESIGN: Prospective, randomized, blinded laboratory evaluation. SETTING:
      University teaching hospital. ANIMALS: Ten healthy adult dogs. INTERVENTIONS:
      Jugular venipuncture and in vitro evaluation for detection of EG in canine blood.
      MEASUREMENTS: Whole blood samples were centrifuged and separated, and the plasma
      was divided into 30 aliquots. The aliquots were mixed with EG to provide EG
      concentrations ranging from 0 to 100 mg/dL. The EG concentration of each sample
      was confirmed using gas chromatography. For the VetSpec EG Qualitative Reagent
      Test Kit, 100 MUL of each sample was added to test vials and compared with 20 and
      50 mg/dL reference vials. For the Kacey EG Test Strips, 20 MUL of each sample was
      added to the test circle and compared with the color chart provided by the
      manufacturer. For each test, samples were prepared in groups of 5 and presented
      in randomized order to 2 readers who were blinded to the presumed EG
      concentration. Samples were scored as negative, 20-50 mg/dL, or greater than 50
      mg/dL. For each test, the sensitivity and specificity for detecting EG was
      calculated. Cohen's unweighted kappa coefficient was calculated to determine the
      degree of agreement between readers. MAIN RESULTS: For detecting EG, the Kacey EG
      Test Strips had excellent sensitivity and specificity (both 100%) and good
      agreement between readers. The VetSpec EG Qualitative Reagent Test Kit was less
      sensitive and specific (65% and 70% for the first reader, 95% and 40% for the
      second) with less agreement. CONCLUSIONS: Of the 2 systems evaluated, the Kacey
      EG Test Strips displayed greater accuracy and ease of use.

PMID- 25047757
TI  - Benefit of endermology on indurations and panniculitis/lipoatrophy during
      relapsing-remitting multiple sclerosis long-term treatment with glatiramer
      acetate.
AB  - INTRODUCTION: Use of endermology (Endermologie(r)), which consists of a deep
      mechanical massage, in patients with multiple sclerosis receiving glatiramer
      acetate suggested improvements in injection-site indurations and
      panniculitis/lipoatrophy in our previous pilot experience. We aimed to assess the
      effect of endermology in a larger population of patients with multiple sclerosis
      receiving glatiramer acetate in clinical practice. METHODS: This was the
      extension phase of our pilot experience, carried out in patients with relapsing
      remitting multiple sclerosis (RRMS) and indurations and/or
      panniculitis/lipoatrophy associated with long-term glatiramer acetate
      administration. Patients underwent endermology sessions twice per week, for 6
      weeks, according to clinical practice. RESULTS: Seventy evaluable patients were
      included (mean age, 42.7+/-9.3 years; female, 95.7%; mean multiple sclerosis
      duration, 9.2+/-8.6 years; mean glatiramer acetate duration, 46.7+/-29.9 months).
      Fifty (71.4%) patients showed indurations and 58 (82.9%)
      panniculitis/lipoatrophy. After 12 endermology sessions, the number of patients
      with indurations significantly decreased (71.4% vs. 28.6%; p<0.001), as did the
      number of their indurations (4.2+/-3.6 vs. 3.7+/-3.4; p<0.001). Although the
      number of patients with panniculitis/lipoatrophy did not significantly decrease,
      there was a significant reduction in the number of areas of
      panniculitis/lipoatrophy (4.3+/-2.6 vs. 3.9+/-2.2; p<0.05). Forty-nine (98.0%)
      patients with indurations and 57 (98.3%) patients with panniculitis/lipoatrophy
      felt satisfied/very satisfied with treatment and considered endermology
      useful/very useful. Endermology was well tolerated, as some pain was reported in
      eight (11.4%) patients, discomfort in three (4.3%) patients, and local
      blotch/swelling and transient bruise in one (1.4%) patient each. Endermology
      enabled glatiramer acetate tolerance to be enhanced in 42 (60.0%) patients.
      CONCLUSION: This project represents the largest experience available supporting
      the benefit of endermology in the reduction/disappearance of indurations and
      improvement in panniculitis/lipoatrophy in patients with RRMS receiving long-term
      glatiramer acetate treatment. Moreover, these benefits also contributed to
      enhancing glatiramer acetate tolerance.

PMID- 25047756
TI  - Parental reports of behavioural outcome among paediatric leukaemia survivors in
      Malaysia: a single institution experience.
AB  - OBJECTIVES: To determine the behavioural impact of chemotherapy in survivors of
      acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to
      identify treatment-related or sociodemography-related factors that might be
      associated with behavioural outcome. METHODS: We examined 57 survivors of
      childhood ALL, who were off treatment for at least 2 years and were in remission,
      aged 4-18 years, and 221 unrelated healthy controls. The Child Behaviour
      Checklist (CBCL) parent report was used either in English or in Bahasa Malaysia
      (the national language of Malaysia) to assess the behavioural outcome. RESULTS:
      Childhood ALL survivors had significantly higher scores on externalising
      behaviour on the CBCL parent report than did controls. Higher problem scores were
      found in ALL survivors with single parents on 'total problems' (P = 0.03) and
      subscales 'withdrawn' (P = 0.03), 'social problems' (P < 0.01) and 'delinquent
      behaviour' (P = 0.03) than in survivors with married parents. Significant
      associations were seen between a lower education level of the father and the
      variables representing internalising (withdrawn, anxious/depressed) and
      externalising (aggressive behaviour). We observed trends on higher scores in all
      scales in ALL survivors with single parents than in controls with single parents
      or with fathers with low education level, especially primary education only.
      CONCLUSIONS: Malaysian childhood ALL survivors had a significantly increased risk
      for externalising behavioural problems, and there was a trend towards increased
      risk of problems in many other behavioural scales. Understanding the
      sociocultural dimension of patients' health is important to be able to design the
      most appropriate remedy for problem behaviours detected in this multi-ethnic
      population.

PMID- 25047758
TI  - Thromboembolic events among patients with hepatitis C virus infection and
      cirrhosis: a matched-cohort study.
AB  - INTRODUCTION: Portal vein thrombosis is a known risk among patients with
      cirrhosis, but the incidence of other thromboembolic events among patients with
      liver disease is inadequately delineated. This study examined the incidence of
      venous and arterial thromboembolic events in patients with cirrhosis and
      hepatitis C virus (HCV) infection and matched comparators. METHODS: Patients
      diagnosed with HCV or cirrhosis of various etiologies were identified from a
      large medical claims database and matched by age and sex to comparator cohorts.
      New-onset diagnoses of venous and arterial thromboembolic events were determined.
      The incidence rate of each event was calculated and rate ratios computed using
      Poisson regression models, adjusting for baseline factors. RESULTS: The study
      included 22,733 HCV-infected patients and 68,198 comparators, and 15,158
      cirrhosis patients and 45,473 comparators. The incidence of any thromboembolic
      event was 233.4 events per 10,000 person-years for the HCV cohort and 138.5 per
      10,000 person-years for the comparators; the adjusted incidence rate ratio for
      any thromboembolic event was 1.62 (95% confidence interval [CI]: 1.48-1.77). For
      the cirrhosis patients and comparators, the crude rates of any thromboembolic
      event were 561.1 and 249.7 per 10,000 person-years, respectively. The adjusted
      incidence rate ratio was 2.28 (95% CI: 2.11-2.47). Arterial events, especially
      unstable angina and transient ischemic attack, were the most frequent events seen
      in both the HCV and cirrhosis cohorts, but venous events, especially portal vein
      thrombosis, showed a more pronounced elevation in patients with liver disease.
      CONCLUSIONS: Patients with HCV and cirrhosis of various etiologies are at
      increased risk of several types of thromboembolic events. Physicians should
      consider this increased risk when managing patients with liver disease.

PMID- 25047759
TI  - Sense of community responsibility in community collaboratives: advancing a theory
      of community as resource and responsibility.
AB  - This paper contributes to the growing body of scholarship aimed at advancing our
      understanding of the experience of community by empirically investigating sense
      of community responsibility (SOC-R) in relation to traditional measures of sense
      of community (SOC) and indices of satisfaction, engagement, and leadership in
      interorganizational collaborative settings. Findings support the proposition
      that, although both are related to the experience of community, SOC and SOC-R
      emphasize different aspects of that experience and operate under different
      theoretical mechanisms of influence. SOC emphasizes community as a resource which
      was found to be a more salient aspect in differentiating those who will be more
      or less satisfied with their experience. In addition, SOC was found to predict
      general participation in a community collaborative. SOC-R emphasizes the
      experience of community as a responsibility which appears to be a stronger
      predictor in explaining higher order engagement requiring greater investment of
      time and resources. Even more importantly, this study indicates that SOC-R is
      uniquely equipped to help us advance models of community leadership. As such, it
      represents an important contribution to expanding our understanding of the
      factors that drive members' willingness to give of themselves toward collective
      aims.

PMID- 25047760
TI  - Easily accessible auxiliary for palladium-catalyzed intramolecular amination of
      C(sp2)-H and C(sp3)-H bonds at delta- and epsilon-positions.
AB  - An easily synthesized and accessible N,O-bidentate auxiliary has been developed
      for selective C-H activation under palladium catalysis. The novel auxiliary
      showed its first powerful application in C-H functionalization of remote
      positions. Both C(sp(2))-H and C(sp(3))-H bonds at delta- and epsilon-positions
      were effectively activated, thus giving tetrahydroquinolines, benzomorpholines,
      pyrrolidines, and indolines in moderate to excellent yields by palladium
      catalyzed intramolecular C-H amination.

PMID- 25047761
TI  - An algorithm for automated detection, localization and measurement of local
      calcium signals from camera-based imaging.
AB  - Local Ca(2+) transients such as puffs and sparks form the building blocks of
      cellular Ca(2+) signaling in numerous cell types. They have traditionally been
      studied by linescan confocal microscopy, but advances in TIRF microscopy together
      with improved electron-multiplied CCD (EMCCD) cameras now enable rapid (>500
      frames s(-1)) imaging of subcellular Ca(2+) signals with high spatial resolution
      in two dimensions. This approach yields vastly more information (ca. 1 Gb min(
      1)) than linescan imaging, rendering visual identification and analysis of local
      events imaged both laborious and subject to user bias. Here we describe a routine
      to rapidly automate identification and analysis of local Ca(2+) events. This
      features an intuitive graphical user-interfaces and runs under Matlab and the
      open-source Python software. The underlying algorithm features spatial and
      temporal noise filtering to reliably detect even small events in the presence of
      noisy and fluctuating baselines; localizes sites of Ca(2+) release with sub-pixel
      resolution; facilitates user review and editing of data; and outputs time
      sequences of fluorescence ratio signals for identified event sites along with
      Excel-compatible tables listing amplitudes and kinetics of events.

PMID- 25047762
TI  - A combination of nuclear beta-catenin and atypical scores as useful diagnostic
      markers for borderline malignancy of gastric tumours.
AB  - AIMS: Although recent advances in endoscopic technology, including submucosal
      dissection (ESD), contribute to significant improvement in detection and
      treatment for early gastric carcinomas (GCas), discrepant diagnosis between
      forceps biopsied and ESD sections sometimes occurs. Here, we focused on
      histological markers for accurate diagnosis of gastric tumours in forceps
      biopsied samples before ESD treatment. METHODS AND RESULTS: A total of 136 cases
      of gastric tumours, including 25 adenomas and 111 GCas, were investigated using a
      combination of forceps biopsied and ESD samples. Atypical scores based on both
      nuclear and branching parameters could distinguish between adenomas and GCas in
      both samples. The labelling indices (LIs) of nuclear beta-catenin were
      significantly higher in GCas than adenomas, and positively correlated with
      atypical scores, as well as branching parameters. In addition, nuclear beta
      catenin immunoreactivity showing small cluster pattern was colocalized with
      immunoreactivity for aldehyde dehydrogenase 1 (ALDH1), known as a cancer stem
      cell (CSC) marker, which suggests the presence of some CSC population, and may be
      due to formation of dynamic tubular branching in GCas. CONCLUSIONS: A combination
      of nuclear beta-catenin and atypical scores may be useful for differential
      diagnosis of borderline malignancy of gastric tumours.

PMID- 25047763
TI  - The evolution of mild parkinsonian signs in aging.
AB  - The progression of mild parkinsonian signs in the absence of idiopathic
      Parkinson's disease in aging is unclear. This study aims to identify predictors
      of the evolution of mild parkinsonian signs in non-demented older adults. Two
      hundred ten participants (76.25 +/- 7.10 years, 57% women) were assessed at
      baseline and 1-year follow-up. Mild parkinsonian signs were defined as the
      presence of bradykinesia, rigidity and/or rest tremor. Depending upon the
      presence of these features at baseline and follow-up, participants were divided
      into one of four groups (no, transient, persistent or new-onset mild parkinsonian
      signs). Physical function was assessed using gait velocity. Ninety-five
      participants presented with mild parkinsonian signs at baseline. At 1-year follow
      up, 59 demonstrated persistent mild parkinsonian signs, while 36 recovered (i.e.,
      transient). Participants with persistent mild parkinsonian signs were older
      (79.66 +/- 7.15 vs. 75.81 +/- 7.37 years, p = 0.01) and evidenced slower gait
      velocity (90.41 +/- 21.46 vs. 109.92 +/- 24.32 cm/s, p < 0.01) compared to those
      with transient mild parkinsonian signs. Gait velocity predicted persistence of
      mild parkinsonian signs, even after adjustments (OR: 0.96, 95% CI: 0.94-0.98).
      Fifty-five participants demonstrated new-onset of mild parkinsonian signs. In
      comparison to participants without mild parkinsonian signs, presence of
      cardiovascular but not cerebrovascular disease at baseline was associated with
      new-onset mild parkinsonian signs. Our study reveals that gait velocity was the
      main predictor of persistent mild parkinsonian signs, whereas cardiovascular
      disease was associated with new-onset mild parkinsonian signs. These findings
      suggest a vascular mechanism for the onset of mild parkinsonian signs and a
      different mechanism, possibly neurodegenerative, for the persistence of mild
      parkinsonian signs.

PMID- 25047764
TI  - Electronic readout enzyme-linked immunosorbent assay with organic field-effect
      transistors as a preeclampsia prognostic.
AB  - Organic field-effect transistor (OFET) sensors can meet the need for portable and
      real-time diagnostics. An electronicreadout enzyme-linked immunosorbent assay
      using OFETs for the detection of a panel of three biomarkers in complex media to
      create a pre-eclampsia prognostic is demonstrated, along with biodetection
      utilizing a fully inkjet-printed and flexible OFET to underscore our ability to
      produce disposable devices. 

PMID- 25047767
TI  - Commentary to: pelvic floor muscle training can reduce prolapse symptoms in women
      with pelvic organ prolapse.

PMID- 25047765
TI  - Motivation, effort and life circumstances as predictors of foot ulcers and
      amputations in people with Type 2 diabetes mellitus.
AB  - AIM: To investigate the predictive value of both patients' motivation and effort
      in their management of Type 2 diabetes and their life circumstances for the
      development of foot ulcers and amputations. METHODS: This study was based on the
      Diabetes Care in General Practice study and Danish population and health
      registers. The associations between patient motivation, effort and life
      circumstances and foot ulcer prevalence 6 years after diabetes diagnosis and the
      incidence of amputation in the following 13 years were analysed using odds ratios
      from logistic regression and hazard ratios from Cox regression models,
      respectively. RESULTS: Foot ulcer prevalence 6 years after diabetes diagnosis was
      2.93% (95% CI 1.86-4.00) among 956 patients. General practitioners' indication of
      'poor' vs 'very good' patient motivation for diabetes management was associated
      with higher foot ulcer prevalence (odds ratio 6.11, 95% CI 1.22-30.61). The same
      trend was seen for 'poor' vs 'good' influence of the patient's own effort in
      diabetes treatment (odds ratio 7.06, 95% CI 2.65-18.84). Of 1058 patients
      examined at 6-year follow-up, 45 experienced amputation during the following 13
      years. 'Poor' vs 'good' influence of the patients' own effort was associated with
      amputation (hazard ratio 7.12, 95% CI 3.40-14.92). When general practitioners
      assessed the influence of patients' life circumstances as 'poor' vs 'good', the
      amputation incidence increased (hazard ratio 2.97, 95% CI 1.22-7.24). 'Poor' vs
      'very good' patient motivation was also associated with a higher amputation
      incidence (hazard ratio 7.57, 95% CI 2.43-23.57), although not in fully adjusted
      models. CONCLUSIONS: General practitioners' existing knowledge of patients' life
      circumstances, motivation and effort in diabetes management should be included in
      treatment strategies to prevent foot complications.

PMID- 25047768
TI  - The rise and fall of infectious diseases: Australian perspectives, 1914-2014.
AB  - Australia has been fortunate in its experience with infectious diseases over the
      past century. By the 1960s, many communicable diseases were controlled through a
      combination of high living standards, progressive adoption of vaccines and
      antimicrobial treatment. Australian medical scientists have made substantial
      contributions to the understanding of many historically significant communicable
      diseases and global initiatives for control. New challenges have emerged as
      previously unrecognised viral infections have emerged, and microbial resistance
      to antibiotics has developed in many old pathogens. Ongoing evolutionary forces,
      both environmental and social, change the balance between humans and microbes.
      The effects of these forces are most sorely felt in poor countries and
      communities. 

PMID- 25047769
TI  - Changing discourses in Aboriginal and Torres Strait Islander health research,
      1914-2014.
AB  - Aboriginal and Torres Strait Islander people strongly assert that health research
      has contributed little to improving their health, in spite of its obvious
      potential. The health concerns of Aboriginal and Torres Strait Islander people
      were largely ignored in early research published in the MJA, which reflected
      broader colonial history and racial discourses. This began to change with the
      demise of scientific racism, and changed policies and political campaigns for
      equal treatment of Indigenous people after the Second World War. In response to
      pressure from Aboriginal and Torres Strait Islander people and organisations, in
      parallel to broader political struggles for Indigenous rights since the 1970s,
      there have been significant and measurable changes to Aboriginal and Torres
      Strait Islander health research. Many of these changes have been about the ethics
      of health research. Increasingly, Aboriginal and Torres Strait Islander
      researchers, communities and organisations are now controlling and decolonising
      health research to better meet their needs, in collaboration with non-Indigenous
      researchers and research organisations. 

PMID- 25047770
TI  - A brief history of medical education and training in Australia.
AB  - Medical education and training in Australia comprises four phases: basic
      education, prevocational training, vocational training and continuing
      professional development. Between the 1860s and 1960s, eight medical schools were
      established in Australia, admitting school leavers to courses comprised of
      preclinical, paraclinical and clinical phases. Between the 1970s and the 1990s,
      two innovative new schools were established and all schools made major reforms to
      student selection, curricula and teaching, learning and assessment methods. Since
      2000, student numbers expanded rapidly, both in existing medical schools and in
      eight new schools established to meet workforce demands, particularly in the
      rural sector. Prevocational training, first introduced as a compulsory internship
      year in the 1930s, has undergone reform and extension to subsequent years of
      junior doctor training through the agency of health departments and postgraduate
      medical education councils. Vocational training and continuing professional
      development, delivered by 15 specialist medical colleges, has evolved since the
      1930s from a focus on specialist care of individual patients to include broader
      professional attributes required to manage complex health care systems. The
      Australian Medical Council began accreditation of basic medical education in 1985
      and its remit now extends to all phases of medical education and training. With
      national governance of the entire system of medical education and training now
      achieved, mechanisms exist for flexible integration of all phases of medical
      education to meet the local and global challenges facing Australia's medical
      workforce. 

PMID- 25047771
TI  - How the Pharmaceutical Benefits Scheme began.
AB  - Seventy years ago, the Curtin wartime government introduced legislation for a
      Pharmaceutical Benefits Scheme (PBS). It was a response to the need to provide
      access to a wave of antibiotic drugs - sulfonamides, streptomycin, penicillin -
      to the whole population, not only to the minority able to afford them. The scheme
      was immediately and successfully opposed by doctors and the conservative
      opposition, which saw in universal health care an underhand plan to nationalise
      medicine. There were two High Court challenges, two referendums and a
      constitutional amendment; but it was not until 1960 that Australians had the
      comprehensive PBS envisaged by Curtin in 1944. 

PMID- 25047772
TI  - A brief history of the specialties from Federation to the present.

PMID- 25047773
TI  - Non-communicable diseases and implications for medical practice in Australia: a
      framework for analysis.
AB  - Non-communicable diseases (NCDs) have become leading causes of mortality and
      morbidity as part of historical epidemiological, demographic and nutritional
      transitions. There has been considerable historical analysis of the immediate and
      underlying causes of this change in the impacts of communicable diseases and
      NCDs, but far less historical analysis of how this transition has shaped medical
      practice. We lay out a framework for future historical analysis by proposing four
      domains of inquiry into key areas of change: changes in the concept of disease;
      evolution of medical technology; changes in workforce, including variation in
      roles and emerging areas of specialisation; and changes in health care structures
      including models of care, government responses and transitioning health systems.
      Our aim is to encourage analysis that takes into account key features in each of
      the four domains, thus enabling a more complete understanding of why, how and
      under what circumstances NCDs have had an effect on medical practice. 

PMID- 25047774
TI  - Introduction to a centenary history of Australian medicine.

PMID- 25047775
TI  - A history of health and medical research in Australia.
AB  - Health and medical research has played an important role in improving the life of
      Australians since before the 20th century, with many Australian researchers
      contributing to important advances both locally and internationally. The
      establishment of the National Health and Medical Research Council (NHMRC) to
      support research and to work to achieve the benefits of research for the
      community was significant. The NHMRC has also provided guidance in research and
      health ethics. Australian research has broadened to include basic biomedical
      science, clinical medicine and science, public health and health services. In
      October 2002, the NHMRC adopted Indigenous health research as a strategic
      priority. In 2013, government expenditure through the NHMRC was $852.9 million.
      This article highlights some important milestones in the history of health and
      medical research in Australia. 

PMID- 25047776
TI  - Reflections on the history of general practice in Australia.
AB  - General practice has experienced change over the past century driven by a variety
      of influences, the most important of which have been changes in the health needs
      of the population, the organisation of the workforce, and medicine itself. Over
      this time, general practice has developed as a profession through education and,
      ultimately, recognition of its specialist qualifications. There has been
      increasing organisational sophistication at the practice, regional and national
      levels. Despite contested scope of practice and vision of its future, general
      practice's place in the health system as a whole has been increasingly recognised
      and affirmed. 

PMID- 25047777
TI  - Medicine in colonial Australia, 1788-1900.
AB  - For the first five decades of European settlement in Australia, medical care for
      convicts and free settlers was provided by the Colonial Medical Service. After
      about 1850, as population and wealth grew markedly, there was significant
      professional development based on private practice. Except in Victoria, medical
      societies and journals did not become solidly established until late in the 19th
      century. The advent of local British Medical Association branches was an
      important factor in this consolidation. In the first few years of the colony,
      mortality was very high, but the common childhood infections were absent until
      the 1830s. From the 1880s, there was a sustained decline in mortality from
      communicable diseases, and therefore in aggregate mortality, while maternal
      mortality remained high. Australian practitioners quickly took up advances in
      practice from overseas, such as antisepsis and diphtheria antitoxin. They shared
      in the international growth in the status of medicine, which was conferred by the
      achievements of bacteriology in particular. From 1813, students were apprenticed
      in Sydney and Hobart and then travelled to Britain to obtain corporate
      qualifications. Medical schools were ultimately opened in the new universities in
      Melbourne (in 1862), Sydney (1883) and Adelaide (1885). The first female student
      was admitted to medicine in Sydney in 1885. Medical politics were intense. The
      outlawing of practice by unorthodox practitioners proved to be an unattainable
      goal. In the latter half of the 19th century, doctors saw chemists as unfair
      competitors for patients. The main medicopolitical struggle was with the mutual
      aid friendly societies, which funded basic medical care for a significant
      proportion of the population until well into the 20th century. The organised
      profession set out to overcome the power of the lay-controlled societies in
      imposing an unacceptable contract system on doctors, even if, historically, the
      guaranteed income was a sine qua non of practice in poorer areas. 

PMID- 25047778
TI  - Understanding the mechanisms of action of antiangiogenic agents in metastatic
      colorectal cancer: a clinician's perspective.
AB  - Multiple clinical trials using bevacizumab, ziv-aflibercept, and regorafenib have
      recently demonstrated efficacy for patients with metastatic colorectal cancer.
      While the net clinical benefit of each of these therapies in the second-line and
      refractory disease setting appears to be similar, important distinctions exist
      between the agents at the pharmacodynamic, tumor microenvironment, and clinical
      levels. The purpose of this review is to survey the preclinical evidence
      regarding the mechanisms of action of these novel antiangiogenic agents and
      provide an overview of their respective clinical activity, while highlighting
      distinctions between therapies. Fundamental understanding of these distinctions
      may aid in clinical decisions and choice of antiangiogenic therapies. 

PMID- 25047782
TI  - Human pain in a dish: Native DRG neurons and differentiated pluripotent stem
      cells.

PMID- 25047781
TI  - Differential structural and resting state connectivity between insular
      subdivisions and other pain-related brain regions.
AB  - Functional neuroimaging studies suggest that the anterior, mid, and posterior
      division of the insula subserve different functions in the perception of pain.
      The anterior insula (AI) has predominantly been associated with cognitive
      affective aspects of pain, while the mid and posterior divisions have been
      implicated in sensory-discriminative processing. We examined whether this
      functional segregation is paralleled by differences in (1) structural and (2)
      resting state connectivity and (3) in correlations with pain-relevant
      psychological traits. Analyses were restricted to the 3 insular subdivisions and
      other pain-related brain regions. Both type of analyses revealed largely
      overlapping results. The AI division was predominantly connected to the
      ventrolateral prefrontal cortex (structural and resting state connectivity) and
      orbitofrontal cortex (structural connectivity). In contrast, the posterior insula
      showed strong connections to the primary somatosensory cortex (SI; structural
      connectivity) and secondary somatosensory cortex (SII; structural and resting
      state connectivity). The mid insula displayed a hybrid connectivity pattern with
      strong connections with the ventrolateral prefrontal cortex, SII (structural and
      resting state connectivity) and SI (structural connectivity). Moreover, resting
      state connectivity revealed strong connectivity of all 3 subdivisions with the
      thalamus. On the behavioural level, AI structural connectivity was related to the
      individual degree of pain vigilance and awareness that showed a positive
      correlation with AI-amygdala connectivity and a negative correlation with AI
      rostral anterior cingulate cortex connectivity. In sum, our findings show a
      differential structural and resting state connectivity for the anterior, mid, and
      posterior insula with other pain-relevant brain regions, which might at least
      partly explain their different functional profiles in pain processing. 

PMID- 25047783
TI  - Distinct brain mechanisms support spatial vs temporal filtering of nociceptive
      information.
AB  - The role of endogenous analgesic mechanisms has largely been viewed in the
      context of gain modulation during nociceptive processing. However, these
      analgesic mechanisms may play critical roles in the extraction and subsequent
      utilization of information related to spatial and temporal features of
      nociceptive input. To date, it remains unknown if spatial and temporal filtering
      of nociceptive information is supported by similar analgesic mechanisms. To
      address this question, human volunteers were recruited to assess brain activation
      with functional magnetic resonance imaging during conditioned pain modulation
      (CPM) and offset analgesia (OA). CPM provides one paradigm for assessing spatial
      filtering of nociceptive information while OA provides a paradigm for assessing
      temporal filtering of nociceptive information. CPM and OA both produced
      statistically significant reductions in pain intensity. However, the magnitude of
      pain reduction elicited by CPM was not correlated with that elicited by OA across
      different individuals. Different patterns of brain activation were consistent
      with the psychophysical findings. CPM elicited widespread reductions in regions
      engaged in nociceptive processing such as the thalamus, insula, and secondary
      somatosensory cortex. OA produced reduced activity in the primary somatosensory
      cortex but was associated with greater activation in the anterior insula,
      dorsolateral prefrontal cortex, intraparietal sulcus, and inferior parietal
      lobule relative to CPM. In the brain stem, CPM consistently produced reductions
      in activity, while OA produced increases in activity. Conjunction analysis
      confirmed that CPM-related activity did not overlap with that of OA. Thus,
      dissociable mechanisms support inhibitory processes engaged during spatial vs
      temporal filtering of nociceptive information. 

PMID- 25047784
TI  - Association of single nucleotide polymorphisms in the lens epithelium-derived
      growth factor (LEDGF/p75) with HIV-1 infection outcomes in Brazilian HIV-1+
      individuals.
AB  - The lens epithelium-derived growth factor p75 (LEDGF/p75), coded by the PSIP1
      gene, is an important host co-factor that interacts with HIV-1 integrase to
      target integration of viral cDNA into active genes. The aim of this study was to
      investigate the association of SNPs in the PSIP1 gene with disease outcome in HIV
      1 infected patients. We performed a genetic association study in a cohort of 171
      HIV-1 seropositive Brazilian individuals classified as rapid progressors (RP, n =
      69), typical progressors (TP, n = 79) and long-term nonprogressors (LTNP, n =
      23). The exonic SNP rs61744944 and 9 tag SNPs were genotyped. A group of 192
      healthy subjects was analyzed to determine the frequency of SNPs and haplotypes
      in the general population. Linkage disequilibrium (LD) analyses indicated that
      the SNPs analyzed were not in high LD (r2<0.8). Logistic regression models
      suggested that patients carrying the T allele rs61744944 (472L) were more likely
      to develop a LTNP phenotype (OR = 4.98; p = 0.05) as compared to TP group. The
      same trend was observed when LTNPs were compared to the RP group (OR = 3.26).
      Results of haplotype analyses reinforced this association, since the OR values
      obtained for the haplotype carrying allele T at rs61744944 also reflected an
      association with LTNP status (OR = 6.05; p = 0.08 and OR = 3.44; p = 0.12 for
      comparisons to TP and RP, respectively). The rare missense variations Ile436Ser
      and Thr473Ile were not identified in the patients enrolled in this study. Gene
      expression analyses showed lower LEDGF/p75 mRNA levels in peripheral blood
      mononuclear cells obtained from HIV-1 infected individuals. However, these levels
      were not influenced by any of the SNPs investigated. In spite of the limited
      number of LTNPs, these data suggest that the PSIP1 gene could be associated with
      the outcome of HIV-1 infection. Further analyses of this gene may guide the
      identification of causative variants to help predict disease course. 

PMID- 25047785
TI  - Maternal depressive symptoms and healthcare expenditures for publicly insured
      children with chronic health conditions.
AB  - This study estimated the prevalence of maternal depressive symptoms and tested
      associations between maternal depressive symptoms and healthcare utilization and
      expenditures among United States publicly insured children with chronic health
      conditions (CCHC). A total of 6,060 publicly insured CCHC from the 2004-2009
      Medical Expenditure Panel Surveys were analyzed using negative binomial models to
      compare healthcare utilization for CCHC of mothers with and without depressive
      symptoms. Annual healthcare expenditures for both groups were compared using a
      two-part model with a logistic regression and generalized linear model. The
      prevalence of depressive symptoms among mothers with CCHC was 19 %. There were no
      differences in annual healthcare utilization for CCHC of mothers with and without
      depressive symptoms. Maternal depressive symptoms were associated with greater
      odds of ED expenditures [odds ratio (OR) 1.26; 95 % CI 1.03-1.54] and lesser odds
      of dental expenditures (OR 0.81; 95 % CI 0.66-0.98) and total expenditures (OR
      0.71; 95 % CI 0.51-0.98). Children of symptomatic mothers had lower predicted
      outpatient expenditures and higher predicted expenditures for total health,
      prescription medications, dental care; and office based, inpatient and ED visits.
      Mothers with CCHC were more likely to report depressive symptoms than were
      mothers with children without chronic health conditions. There were few
      differences in annual healthcare utilization and expenditures between CCHC of
      mothers with and without depressive symptoms. However, having a mother with
      depressive symptoms was associated with higher ED expenditures and higher
      predicted healthcare expenditures in a population of children who comprise over
      three-fourths of the top decile of Medicaid spending. 

PMID- 25047786
TI  - Obesity stigma as a determinant of poor birth outcomes in women with high BMI: a
      conceptual framework.
AB  - Obesity stigma has been linked to poor health outcomes on an individual and
      population basis. However, little research has been conducted on the role of
      chronic or recent obesity stigma in the health disparities experienced by
      pregnant women with high body mass index. The purpose of this article is to
      discuss poor birth outcomes in this population from an integrated perinatal
      health framework perspective, incorporating obesity stigma as a social
      determinant. In studies of non-pregnant populations, obesity stigma has been
      associated with stress, unhealthy coping strategies, psychological disorders, and
      exacerbations of physical illness. This article examines the mechanisms by which
      obesity stigma influences health outcomes and suggests how they might apply to
      selected complications of pregnancy, including macrosomia, preterm birth and
      cesarean delivery. Given the rates of obesity and associated pregnancy
      complications in the United States, it is critical to examine the determinants of
      those problems from a life course and multiple determinants perspective. This
      paper offers a conceptual framework to guide exploratory research in this area,
      incorporating the construct of obesity stigma. 

PMID- 25047787
TI  - Healthy start: description of a safety net for perinatal support during disaster
      recovery.
AB  - Publicly funded programs and safety net organizations have key roles during post
      disaster recovery to care for vulnerable populations, including pregnant women
      with low resources. The objective of this study was to compare the health of
      prenatal women who accessed the New Orleans Healthy Start program to those women
      who only used traditional prenatal care (PNC) during long-term recovery from the
      Hurricane Katrina disaster. During 2010-2012, this descriptive, cross-sectional
      study recruited 402 prenatal women (24-40 weeks) from prenatal clinics and
      classes. All women were enrolled in PNC, with 282 experiencing only traditional
      PNC, while 120 women added Healthy Start participation to their usual PNC.
      Measures were obtained to determine, past hurricane experience, hurricane
      recovery, perceptions of prenatal care, mental health, and birth outcomes. Women
      accessing Healthy Start-New Orleans were more socially "at risk" (younger, lower
      income, not living with a partner, African American), lived through more
      hurricane trauma, and had a higher incidence of depression (40 %) and post
      traumatic stress disorder (PTSD) (15 %) than women in traditional PNC (29 %
      depression; 6.1 % PTSD). Women using Healthy Start reported more mental health
      counseling and prenatal education than did women in only traditional PNC. Birth
      outcomes were similar in the two groups. The Healthy Start participants with less
      resources and more mental health difficulties after disaster, represented a more
      vulnerable population in need of additional support. This study underscores the
      necessity for community and governmental programs to develop disaster response
      plans that address needs of vulnerable populations during prolonged recovery. 

PMID- 25047788
TI  - Characteristics associated with breastfeeding behaviors among urban versus rural
      women enrolled in the Kansas WIC program.
AB  - The Special Supplemental Nutrition Program for Women, Infants and Children (WIC)
      is a public nutritional assistance program for low-income women and their
      children up to age five. This study provides insight into maternal
      characteristics associated with breastfeeding among urban versus rural women. A
      secondary analysis was conducted using the Pregnancy Nutrition Surveillance
      System dataset of women enrolled in the Kansas WIC program in 2011. Geographic
      residency status was obtained through application of the Census tract-based rural
      urban commuting area codes. Descriptive variables included maternal demographics,
      health, and lifestyle behaviors. A multivariable binary logistic regression was
      used to obtain adjusted odds ratios with 95 % confidence intervals. The outcome
      variable was initiation of breastfeeding. A P value of <=0.05 was considered
      statistically significant. The total sample size was 17,067 women. Statistically
      significant differences regarding socio-demographics, program participation, and
      health behaviors for urban and rural WIC participants were observed. About 74 %
      of all WIC mothers initiated breastfeeding. Urban women who were Hispanic, aged
      18-19, high school graduates, household income >$10,000/year, and started early
      prenatal care were more likely to breastfeed. Urban and rural women who were non
      Hispanic black with some high school education were less likely to breastfeed.
      Increased breastfeeding initiation rates are the result of a collaborative effort
      between WIC and community organizations. Availability of prenatal services to
      rural women is critical in the success of breastfeeding promotion. Findings help
      inform WIC program administrators and assist in enhancing breastfeeding services
      to the Kansas WIC population. 

PMID- 25047789
TI  - Influence of age and gender on Doppler index of diastolic function in Chinese
      hypertensive patients.
AB  - AIM: This paper explores age- and gender-specific changes in Doppler
      echocardiographic index-E' of left ventricular diastolic function. METHODS: The
      study involved 366 hypertensive patients (197 men and 169 women) who were aged
      from 20 to 90 years (mean 58.60 +/- 15.68 years), without a diagnosis of any
      other disease. Early diastolic mitral inflow velocity (E), late diastolic mitral
      annular velocity (A), and E/A ratio were measured with pulse wave Doppler. Early
      diastolic mitral annular velocity (E') and E/E' ratios were measured with tissue
      Doppler imaging of lateral mitral annulus. Diastolic indices were highly
      correlated with age. RESULTS: Among those aged 20-29, E' was significantly higher
      in female than in male. In patients aged 30-39, 40-49, 50-59, 60-69 and 70-79
      years, E' was similar in both genders. Among those aged 80-89 years, E' was
      significantly lower in female than in male. Overall (n = 366) predictors of the
      lowest quartile of E' (E' < 8.00 cm/s) were age (P < 0.0001; chi(2) = 67.35; OR
      1.28; 95% CI 1.26-1.30) and female gender (P < 0.05; chi(2) = 5.76; OR 1.56; 95%
      CI 1.19-1.94). CONCLUSIONS: Age-related changes in diastolic indices correlated
      with gender among hypertensive patients. Diastolic function deteriorated more
      significantly among elderly women compared with elderly men. The study may
      explain the increased incidence of diastolic heart failure in elderly women with
      hypertension.

PMID- 25047790
TI  - Effect of root canal dimensions, injection rate, and needle design on the apical
      extrusion of an irrigant: an in vitro study.
AB  - AIM: The purpose of this study was to determine the effect of root canal
      dimensions, type of needle, and injection rate on the apical extrusion of an
      irrigant in a simulated root canal. METHODS: Ten students used two types of 28
      gauge needles, to deliver 3 mL irrigant solution into artificial canals prepared
      in acrylic blocks to a standard size of ISO 25, 30, or 40 (0.06 taper; n = 10).
      Each block was preweighed to the nearest microgram before and after irrigation
      once the canal was dried with paper points. This was repeated with a syringe pump
      at a flow rate of 50, 100, 200 or 300 MUL/s with the needle inserted to a
      standard depth. RESULTS: Significant differences were observed between the side
      vented and notched-end needles when the rate of irrigation was higher than 100
      MUL/s, and when the apical size was below ISO 40 (P < 0.001). The amount of
      extrusion was more variable and significantly higher when irrigation was
      performed manually, compared with the syringe pump groups. CONCLUSIONS: Injection
      rates above 100 MUL/s increased the risk of extrusion, whereas increasing the
      apical canal size to ISO 40 reduced the amount of extrusion in all groups. The
      use of a side-vented needle negates the injection-rate effects.

PMID- 25047791
TI  - Effects of anterior cruciate ligament reconstruction on neuromuscular
      tensiomyographic characteristics of the lower extremity in competitive male
      soccer players.
AB  - PURPOSE: To investigate the effects of anterior cruciate ligament (ACL)
      reconstruction on mechanical and contractile properties of the skeletal muscles
      of the lower extremities in soccer players through tensiomyography (TMG).
      METHODS: All soccer players with acute ACL tear included underwent resting TMG
      assessment of muscles of both lower extremities before and 1 year after ACL
      reconstruction. The muscles assessed were vastus medialis (VM), vastus laterals
      (VL), rectus femoris (RF), semitendinosus (ST), biceps femoris (BF),
      gastrocnemius medialis (GM), and gastrocnemius lateralis (GL). The TMG parameters
      obtained for each muscle were maximal displacement (D m), delay time (T d),
      contraction time (T c), sustained time (T s), and half-relaxation time (T r).
      RESULTS: The injured leg had a significant decrease in VL-T c, ST-T c, GM-T c, GL
      T r, and GL-T d, and a significant increase in VM-T r and GM-T s in the
      postoperative compared to preoperative period. The non-injured leg demonstrated
      significant preoperative-postoperative changes in the VL, RF, and BF, but not in
      VM, ST, GM, and GL The magnitude of preoperative-postoperative differences in the
      injured leg was significantly higher in RF-T c, ST-T c, BF-D m, and GL-T r, but
      lower in RF-T r and GM-T s, compared to the non-injured leg. Both groups improved
      their symmetry between the quadriceps and hamstring muscle groups in both sides.
      CONCLUSIONS: The quadriceps muscles improved their resistance to fatigue and
      contraction velocity in both sides, and the hamstring muscles improved their
      contraction velocity and muscle tone in both sides as well. Improvements in
      contraction velocity and muscle tone were more evident in the quadriceps and
      hamstrings of the injured compared to the uninjured side. In addition, the
      intervention increased the percentage of symmetry between both sides in the TMG
      of the quadriceps muscles and the balance between ACL-agonist (hamstrings) and
      ACL-antagonist (quadriceps) muscle groups in both sides. This study shows how ACL
      reconstruction (and subsequent rehabilitation) can positively impact
      neuromuscular characteristics of the quadriceps and hamstrings. LEVEL OF
      EVIDENCE: Therapeutic, Level II.

PMID- 25047793
TI  - Return to sport after patellar dislocation or following surgery for
      patellofemoral instability.
AB  - Patellofemoral instability may occur in a young population as a result of injury
      during sporting activities. This review focuses on return to sport after one
      episode of dislocation treated no operatively and as well after surgery for
      chronic patellofemoral instability. With or without surgery, only two-thirds of
      patients return to sports at the same level as prior to injury. A high-quality
      rehabilitation programme using specific exercises is the key for a safe return to
      sporting activities. To achieve this goal, recovery of muscle strength and
      dynamic stability of the lower limbs is crucial. The focus should be directed to
      strengthen the quadriceps muscle and pelvic stabilizers, as well as lateral trunk
      muscle training. Patient education and regularly performed home exercises are
      other key factors that can lead to a successful return to sports. The criteria
      for a safe return to sports include the absence of pain, no effusion, a complete
      range of motion, almost symmetrical strength, and excellent dynamic stability.
      Level of evidence IV. 

PMID- 25047792
TI  - Post-cam mechanics and tibiofemoral kinematics: a dynamic in vitro analysis of
      eight posterior-stabilized total knee designs.
AB  - PURPOSE: Posterior cruciate ligament (PCL)-substituting total knee arthroplasty
      (TKA) designs were introduced to avoid paradoxical roll forward of the femur and
      to optimize knee kinematics. The aim of this in vitro study was to investigate
      post-cam function and contact mechanics and relate it to knee kinematics during
      squatting in eight contemporary posterior-stabilized TKA designs. METHODS: All
      prostheses were fixed on custom-designed metal fixtures and mounted in a knee rig
      and five sequential-loaded squats were performed between 30 degrees  and 130
      degrees  of flexion. Contact pressure and contact area were measured using
      pressure-sensitive Tekscan sensors on the posterior face of the post. Kinematics
      was recorded with reflective markers and infrared light-capturing cameras.
      RESULTS: The post-cam mechanisms analyzed in this study are very variable in
      terms of design features. This leads to large variations in terms of the flexion
      angle at which the post and cam engage maximal contact force, contact pressure
      and contact area. We found that more functional post-cam mechanisms, which engage
      at lower flexion angle and have a similar behavior as normal PCL function,
      generally show more normal rollback and tibial rotation at the expense of higher
      contact forces and pressures. All designs show high contact forces. A positive
      correlation was found between contact force and initial contact angle.
      CONCLUSION: Post-cam contact mechanics and kinematics were documented in a
      standardized setting. Post-cam contact mechanics are correlated with post-cam
      function. Outcomes of this study can help to develop more functional designs in
      future. Nevertheless, a compromise will always be made between functional
      requirements and risk of failure. We assume that more normal knee kinematics
      leads to more patient satisfaction because of better mobility. Understanding of
      the post-cam mechanism, and knowing how this system really works, is maybe the
      clue in further development of new total knee designs.

PMID- 25047794
TI  - Relationship between the alpha and beta angles in diagnosing CAM-type
      femoroacetabular impingement on frog-leg lateral radiographs.
AB  - PURPOSE: Alpha and beta angles are commonly used radiographic measures to assess
      the sphericity of the proximal femur and distance between the pathologic head
      neck junction and the acetabular rim, respectively. The aim of this study was to
      explore the relationship between these two measurements on frog-leg lateral hip
      radiographs. METHODS: Fifty frog-leg lateral hip radiographs were evaluated by
      two orthopaedic surgeons and two radiologists. Each reviewer measured the alpha
      and beta angles on two separate occasions to determine the relationship between
      positive alpha and beta angles and the inter- and intra-observer reliability of
      these measurements. RESULTS: There was no significant association between
      positive alpha and beta angles, [kappa range -0.043 (95 % CI -0.17 to 0.086) to
      0.54 (95 % CI 0.33-0.75)]. Intra-observer reliability was high [alpha angle intra
      class correlation coefficient (ICC) range 0.74 (95 % CI 0.58-0.84) to 0.99 (95 %
      CI 0.98-0.99) and beta angle ICC range 0.86 (95 % CI 0.76-0.92) to 0.97 (95 % CI
      0.95-0.98)]. CONCLUSIONS: There is no statistical or functional relationship
      between readings of positive alpha and beta angles. The radiographic measurements
      resulted in high intra-observer and fair-to-moderate inter-observer reliability.
      Results of this study suggest that the presence of a CAM lesion on lateral
      radiographs as suggested by a positive alpha angle does not necessitate a
      decrease in clearance between the femoral head and acetabular rim as measured by
      the beta angle and thus may not be the best measure of functional impingement.
      Understanding the relationship between these two aspects of femoroacetabular
      impingement improves a surgeon's ability to anticipate potential operative
      management.

PMID- 25047795
TI  - Arthroscopy as a diagnostic tool for painful trunnion corrosion after hip
      arthroplasty.
AB  - PURPOSE: Adverse local soft tissue reactions can occur in response to wear debris
      or corrosion products released from total hip arthroplasty (THA). Hip arthroscopy
      is a useful diagnostic adjunct in the investigation of painful THA. METHODS: A
      patient with a painful primary metal-on-highly cross-linked polyethylene THA
      underwent hip arthroscopy to confirm the diagnosis of trunnion corrosion.
      RESULTS: The prosthetic implants were well fixed and aligned with no indication
      of infection. Hip arthroscopy was used to confirm the presence of corrosion on
      the trunnion of a titanium stem at its junction with a cobalt-chrome head. Due to
      persistent symptoms, the patient subsequently underwent arthrotomy, which
      confirmed the diagnosis, and revision hip arthroplasty to a titanium adapter
      sleeve, ceramic head and liner exchange, with relief of his symptoms. CONCLUSION:
      Hip arthroscopy may prove a useful additional diagnostic tool in the
      investigation of this emerging clinical entity.

PMID- 25047797
TI  - Patients' perspectives of care for type 2 diabetes in Bangladesh -a qualitative
      study.
AB  - BACKGROUND: Worldwide, type 2 diabetes affects approximately 220 million people
      and is the cause of 1.1 million deaths each year, 80% of which occur in low and
      middle income countries (LMICs). Over the next 20 years, prevalence is expected
      to double worldwide and increase by 150% in LMICs. There is now a move towards
      improving care for diabetes. However no information on patients' needs,
      perceptions and experiences is available, hindering effective and appropriate
      changes in policy and practice. We developed a study with the objective of
      understanding patients' experiences of treatment for type 2 diabetes. METHODS:
      During January 2011, we conducted in-depth interviews in five sites across two
      administrative districts of Bangladesh, purposefully chosen to represent
      different geographic regions and local demographics In total, we conducted 23 (14
      male, 9 female) individual interviews across the 5 sites, to gain insight into
      patients' understanding of their diabetes and its management. RESULTS: Patients'
      levels of knowledge and understanding about diabetes and its management is
      depended on where they received their initial diagnosis and care. Away from
      specialist centres, patients had poor understanding of the essential of diabetes
      and its management. No appropriate written or verbal information was available
      for a significant number of patients, compounded limited knowledge and
      understanding of diabetes by healthcare professionals. Patients felt that with
      improved provision of appropriate information they would be able to better
      understand their diabetes and improve their role in its management. Access to
      appropriate diagnosis and subsequent treatment was restricted by availability and
      costs of services. CONCLUSION: Effective, appropriate and essential healthcare
      services for diabetes in Bangladesh is extremely limited, a majority of patients
      receive suboptimal care. Site of diagnosis will impact significantly on the
      quality of information provided and the quality of subsequent treatments.
      Although appropriate services are available at some specialist centres, the
      inability of patients to pay for routine tests and check-ups prevents them from
      receiving timely diagnoses and appropriate continuity of care. The double burden
      of communicable diseases and diseases is now a well-recognised. Emphasis must be
      placed on developing appropriate and effective preventive strategies to address
      this burden.

PMID- 25047796
TI  - Postarthroscopy analgesia using intraarticular levobupivacaine and intravenous
      dexketoprofen trometamol.
AB  - PURPOSE: The aim of this prospective study was to determine the efficacy of
      intraarticular levobupivacaine with and without intravenous dexketoprofen
      trometamol for postarthroscopy analgesia. METHODS: Sixty patients who underwent
      arthroscopic knee surgery were randomly assigned to three treatment groups. When
      the surgical procedure was completed, patients received the following treatments:
      group I (n = 20) patients received 20 mL intraarticular normal saline and 2 mL
      intravenous dexketoprofen trometamol (50 mg); group II (n = 20) patients received
      20 mL intraarticular 0.5 % levobupivacaine (100 mg) and 2 mL intravenous normal
      saline; and group III (n = 20) patients received 20 mL intraarticular 0.5 %
      levobupivacaine (100 mg) and 2 mL intravenous dexketoprofen trometamol (50 mg).
      The visual analogue scale (VAS) was used, and the total analgesic consumption was
      assessed at 1, 2, 4, 6, 12, and 24 h post-operatively. RESULTS: The VAS scores at
      1, 2, 4, 6, 12, and 24 h post-operatively were significantly increased in group I
      and group II compared with group III (p < 0.05). The average VAS score during the
      first 24 h post-operatively was significantly lower in group III than in group I
      and group II (p < 0.001). Total meperidine consumption was significantly lower in
      group III than in groups I and II (p < 0.001). CONCLUSION: Intraarticular
      levobupivacaine with adjuvant intravenous dexketoprofen trometamol administration
      provided better pain relief and less analgesic requirement after arthroscopic
      knee surgery during the first 24 h than that induced by dexketoprofen alone or
      levobupivacaine intraarticular alone. LEVEL OF EVIDENCE: II.

PMID- 25047798
TI  - Inappropriate use of the quasi-reversible electrode kinetic model in simulation
      experiment comparisons of voltammetric processes that approach the reversible
      limit.
AB  - Many electrode processes that approach the "reversible" (infinitely fast) limit
      under voltammetric conditions have been inappropriately analyzed by comparison of
      experimental data and theory derived from the "quasi-reversible" model.
      Simulations based on "reversible" and "quasi-reversible" models have been fitted
      to an extensive series of a.c. voltammetric experiments undertaken at macrodisk
      glassy carbon (GC) electrodes for oxidation of ferrocene (Fc(0/+)) in CH3CN (0.10
      M (n-Bu)4NPF6) and reduction of [Ru(NH3)6](3+) and [Fe(CN)6](3-) in 1 M KCl
      aqueous electrolyte. The confidence with which parameters such as standard formal
      potential (E(0)), heterogeneous electron transfer rate constant at E(0) (k(0)),
      charge transfer coefficient (alpha), uncompensated resistance (Ru), and double
      layer capacitance (CDL) can be reported using the "quasi-reversible" model has
      been assessed using bootstrapping and parameter sweep (contour plot) techniques.
      Underparameterization, such as that which occurs when modeling CDL with a
      potential independent value, results in a less than optimal level of experiment
      theory agreement. Overparameterization may improve the agreement but easily
      results in generation of physically meaningful but incorrect values of the
      recovered parameters, as is the case with the very fast Fc(0/+) and
      [Ru(NH3)6](3+/2+) processes. In summary, for fast electrode kinetics approaching
      the "reversible" limit, it is recommended that the "reversible" model be used for
      theory-experiment comparisons with only E(0), Ru, and CDL being quantified and a
      lower limit of k(0) being reported; e.g., k(0) >= 9 cm s(-1) for the Fc(0/+)
      process. 

PMID- 25047800
TI  - The effects of poly-unsaturated fatty acids on the physiology of hibernation in a
      South American marsupial, Dromiciops gliroides.
AB  - Many mammals hibernate, which is a profound lethargic state of several weeks or
      months during winter, that represents a transitory episode of hetherothermy. As
      with other cases of dormancy, the main benefit of hibernation seems to be energy
      saving. However, the depth and duration of torpor can be experimentally modified
      by the composition of food, especially by fattyacid composition. In eutherians,
      diets rich in unsaturated fatty acids (i.e., fatty acids with at least one double
      bond) lengthen torpor, reduce metabolism and permit hibernation at lower
      temperatures. Here we studied whether diets varying in fatty acid composition
      have an effect on the physiology of hibernation in a South American marsupial,
      Dromiciops gliroides. We designed a factorial experiment where thermal
      acclimation (two levels: natural versus constant temperature) was combined with
      diet acclimation: saturated (i.e., diets with high concentration of saturated
      fatty acids) versus unsaturated (i.e., diets with high concentration of
      unsaturated fatty acids). We measured energy metabolism in active and torpid
      individuals, as well as torpor duration, and a suite of 12 blood biochemical
      parameters. After a cafeteria test, we found that D. gliroides did not show any
      preference for a given diet. Also, we did not find effects of diet on body
      temperature during torpor, or its duration. However, saturated diets, combined
      with high temperatures provoked a disproportionate increase in fat utilization,
      leading to body mass reduction. Those animals were more active, and metabolized
      more fats than those fed with a high proportion of unsaturated fatty acids
      (="unsaturated diets"). These results contrast with previous studies, which
      showed a significant effect of fatty acid composition of diets on food
      preferences and torpor patterns in mammals. 

PMID- 25047799
TI  - Highly selective fluorescence off-on probes for biothiols and imaging in live
      cells.
AB  - Three sulfonyl benzothiazole-based fluorescent probes (, , and ) for the
      detection of biothiols (cysteine, homocysteine, and glutathione) are developed
      based on thiol-mediated nucleophilic aromatic substitutions. The probes exhibited
      good selectivity and sensitivity toward biothiols over other analytes. The probes
      were successfully applied for visualizing endogenous thiols in living cells. 

PMID- 25047802
TI  - Parabens can enable hallmarks and characteristics of cancer in human breast
      epithelial cells: a review of the literature with reference to new exposure data
      and regulatory status.
AB  - A framework for understanding the complexity of cancer development was
      established by Hanahan and Weinberg in their definition of the hallmarks of
      cancer. In this review, we consider the evidence that parabens can enable
      development in human breast epithelial cells of four of six of the basic
      hallmarks, one of two of the emerging hallmarks and one of two of the enabling
      characteristics. In Hallmark 1, parabens have been measured as present in 99% of
      human breast tissue samples, possess oestrogenic activity and can stimulate
      sustained proliferation of human breast cancer cells at concentrations measurable
      in the breast. In Hallmark 2, parabens can inhibit the suppression of breast
      cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen
      related receptor gamma may prevent its deactivation by growth inhibitors. In
      Hallmark 3, in the 10 nm-1 MUm range, parabens give a dose-dependent evasion of
      apoptosis in high-risk donor breast epithelial cells. In Hallmark 4, long-term
      exposure (>20 weeks) to parabens leads to increased migratory and invasive
      activity in human breast cancer cells, properties that are linked to the
      metastatic process. As an emerging hallmark methylparaben has been shown in human
      breast epithelial cells to increase mTOR, a key regulator of energy metabolism.
      As an enabling characteristic parabens can cause DNA damage at high
      concentrations in the short term but more work is needed to investigate long
      term, low-dose mixtures. The ability of parabens to enable multiple cancer
      hallmarks in human breast epithelial cells provides grounds for regulatory review
      of the implications of the presence of parabens in human breast tissue.

PMID- 25047803
TI  - Genome duplication and gene loss affect the evolution of heat shock transcription
      factor genes in legumes.
AB  - Whole-genome duplication events (polyploidy events) and gene loss events have
      played important roles in the evolution of legumes. Here we show that the vast
      majority of Hsf gene duplications resulted from whole genome duplication events
      rather than tandem duplication, and significant differences in gene retention
      exist between species. By searching for intraspecies gene colinearity
      (microsynteny) and dating the age distributions of duplicated genes, we found
      that genome duplications accounted for 42 of 46 Hsf-containing segments in
      Glycine max, while paired segments were rarely identified in Lotus japonicas,
      Medicago truncatula and Cajanus cajan. However, by comparing interspecies
      microsynteny, we determined that the great majority of Hsf-containing segments in
      Lotus japonicas, Medicago truncatula and Cajanus cajan show extensive
      conservation with the duplicated regions of Glycine max. These segments formed 17
      groups of orthologous segments. These results suggest that these regions shared
      ancient genome duplication with Hsf genes in Glycine max, but more than half of
      the copies of these genes were lost. On the other hand, the Glycine max Hsf gene
      family retained approximately 75% and 84% of duplicated genes produced from the
      ancient genome duplication and recent Glycine-specific genome duplication,
      respectively. Continuous purifying selection has played a key role in the
      maintenance of Hsf genes in Glycine max. Expression analysis of the Hsf genes in
      Lotus japonicus revealed their putative involvement in multiple tissue
      /developmental stages and responses to various abiotic stimuli. This study traces
      the evolution of Hsf genes in legume species and demonstrates that the rates of
      gene gain and loss are far from equilibrium in different species. 

PMID- 25047804
TI  - Positive impact of increases in condom use among female sex workers and clients
      in a medium HIV prevalence epidemic: modelling results from Project SIDA1/2/3 in
      Cotonou, Benin.
AB  - BACKGROUND: A comprehensive, HIV prevention programme (Projet Sida1/2/3) was
      implemented among female sex workers (FSWs) in Cotonou, Benin, in 1993 following
      which condom use among FSWs increased threefold between 1993 and 2008 while FSW
      HIV prevalence declined from 53.3% to 30.4%. OBJECTIVE: Estimate the potential
      impact of the intervention on HIV prevalence/incidence in FSWs, clients and the
      general population in Cotonou, Benin. METHODS AND FINDINGS: A transmission
      dynamics model parameterised with setting-specific bio-behavioural data was used
      within a Bayesian framework to fit the model and simulate HIV transmission in the
      high and low-risk population of Cotonou and to estimate HIV incidence and
      infections averted by SIDA1/2/3. Our model results suggest that prior to
      SIDA1/2/3 commercial sex had contributed directly or indirectly to 93% (84-98%)
      of all cumulative infections and that the observed decline in FSWs HIV prevalence
      was more consistent with the self-reported post-intervention increase in condom
      use by FSWs than a counterfactual assuming no change in condom use after 1993 (CF
      1). Compared to the counterfactual (CF-1), the increase in condom use may have
      prevented 62% (52-71%) of new HIV infections among FSWs between 1993 and 2008 and
      33% (20-46%) in the overall population. CONCLUSIONS: Our analysis provides
      plausible evidence that the post-intervention increase in condom use during
      commercial sex significantly reduced HIV prevalence and incidence among FSWs and
      general population. Sex worker interventions can be effective even in medium HIV
      prevalence epidemics and need to be sustained over the long-term.

PMID- 25047805
TI  - Clades and clans: a comparison study of two evolutionary models.
AB  - The Yule-Harding-Kingman (YHK) model and the proportional to distinguishable
      arrangements (PDA) model are two binary tree generating models that are widely
      used in evolutionary biology. Understanding the distributions of clade sizes
      under these two models provides valuable insights into macro-evolutionary
      processes, and is important in hypothesis testing and Bayesian analyses in
      phylogenetics. Here we show that these distributions are log-convex, which
      implies that very large clades or very small clades are more likely to occur
      under these two models. Moreover, we prove that there exists a critical value
      kappa(n) for each n >= 4 such that for a given clade with size k, the probability
      that this clade is contained in a random tree with n leaves generated under the
      YHK model is higher than that under the PDA model if 1 < k < kappa(n),and lower
      if kappa(n) < k < n. Finally, we extend our results to binary unrooted trees, and
      obtain similar results for the distributions of clan sizes.

PMID- 25047806
TI  - Augmented bronchial smooth muscle contractility induced by aqueous cigarette
      smoke extract in rats.
AB  - Cigarette smoking is the main risk factor for the development of chronic
      obstructive pulmonary disease (COPD). However, little is known about the
      mechanisms of cigarette smoke-induced bronchial smooth muscle (BSM)
      hyperresponsiveness. In the present study, we investigated the effects of aqueous
      cigarette smoke extract (ACSE) on the BSM contraction in rats. The bronchial
      strips of rats were incubated with ACSE or control-extract for 24 h. The
      acetylcholine (ACh), high K(+) depolarization and sodium fluoride (NaF)-induced
      BSM contraction of the ACSE-treated group was significantly augmented as compared
      to that of the control one. The expression levels of both myosin light-chain
      kinase (MLCK) and RhoA were significantly increased in the ACSE-treated BSM.
      These findings suggest that the water-soluble components of cigarette smoke may
      cause BSM hyperresponsiveness via an increase in MLCK and RhoA. 

PMID- 25047807
TI  - Coalescence-induced crystallisation wave in Pd nanoparticles.
AB  - Palladium nanoparticles offer an attractive alternative to bulk palladium for
      catalysis, hydrogen storage and gas sensing applications. Their performance
      depends strongly on surface structure; therefore, nanoparticle coalescence can
      play an important role, as it determines the resultant structure of the active
      sites where reactions (e.g. catalysis) actually take place, i.e. facets, edges,
      vertices or protrusions. With this in mind, we performed classical molecular
      dynamics (MD) simulations and magnetron-sputtering inert gas condensation
      depositions of palladium nanoparticles, supported by high-resolution transmission
      electron microscopy (HRTEM), to study the mechanisms that govern their
      coalescence. Surface energy minimisation drove the interactions initially,
      leading to the formation of an interface/neck, as expected. Intriguingly, at a
      later stage, atomic rearrangements triggered a crystallisation wave propagating
      through the amorphous nanoparticles, leading to mono- or polycrystalline fcc
      structures. In the case of crystalline nanoparticles, almost-epitaxial alignment
      occurred and the formation of twins and surface protrusions were observed. 

PMID- 25047808
TI  - Self-efficacy, transition, and patient outcomes in the sickle cell disease
      population.
AB  - Severe pain is a common symptom of sickle cell disease (SCD). Transitions between
      adult and pediatric care are a point of particular vulnerability for patients,
      increasing the risk for poor pain management. The purpose of this literature
      review was to investigate the relationships among self-efficacy, transition, and
      SCD health outcomes. A systematic literature search was performed within CINAHL,
      Academic Search Premier, MEDLINE, and PubMed on published papers between 2003 and
      2013. After applying exclusion criteria, 20 articles were used in the final
      review. Few studies were identified that directly tested the relationship between
      self-efficacy and SCD outcomes. Although there are few studies on this topic,
      most demonstrated positive correlations between self-efficacy during transition
      and positive patient outcomes in the SCD population. Additional studies are
      needed to support causation. Studies were commonly limited by small sample sizes
      and attrition. Furthermore, there is a large gap in the literature regarding how
      self-efficacy can be increased in these patients. Interventions that promote self
      efficacy have the potential to improve SCD pain outcomes, but more research is
      needed to develop interventions to increase these adolescents' self-efficacy. If
      providers can identify individuals in this population with low self-efficacy,
      they may be able to intervene early to improve patient outcomes. Most identified
      studies point to the positive correlation between self-efficacy and positive
      health outcomes in adolescents with SCD. Self-efficacy has the potential to guide
      self-care interventions and further research with the SCD population. 

PMID- 25047809
TI  - Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the
      immune response for hepatitis B viral clearance in mice model.
AB  - Persistent hepatitis B viral (HBV) infection results in chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma (HCC). An efficient control of virus
      infections requires the coordinated actions of both innate and adaptive immune
      responses. In order to define the role of innate immunity effectors against HBV,
      viral clearance was studied in a panel of immunodeficient mouse strains by the
      hydrodynamic injection approach. Our results demonstrate that HBV viral clearance
      is not changed in IFN-alpha/beta receptor (IFNAR), RIG-I, MDA5, MYD88, NLRP3,
      ASC, and IL-1R knock-out mice, indicating that these innate immunity effectors
      are not required for HBV clearance. In contrast, HBV persists in the absence of
      tumor necrosis factor-alpha (TNF-alpha) or in mice treated with the soluble TNF
      receptor blocker, Etanercept. In these mice, there was an increase in PD-1
      expressing CD8+ T-cells and an increase of serum HBV DNA, HBV core, and surface
      antigen expression as well as viral replication within the liver. Furthermore,
      the induction of TNF-alpha in clearing HBV is dependent on the HBV core, and TNF
      blockage eliminated HBV core-induced viral clearance effects. Finally, the intra
      hepatic leukocytes (IHLs), but not the hepatocytes, are the cell source
      responsible for TNF-alpha production induced by HBcAg. These results provide
      evidences for TNF-alpha mediated innate immune mechanisms in HBV clearance and
      explain the mechanism of HBV reactivation during therapy with TNF blockage
      agents. 

PMID- 25047811
TI  - Crystalloids for fluid resuscitation in sepsis: where is the balance?

PMID- 25047810
TI  - Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti
      tumor efficacy: a mathematical model.
AB  - Oncolytic viruses are genetically engineered viruses that are designed to kill
      cancer cells while doing minimal damage to normal healthy tissue. After being
      injected into a tumor, they infect cancer cells, multiply inside them, and when a
      cancer cell is killed they move on to spread and infect other cancer cells.
      Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major
      glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans
      without any deleterious effects in vivo. It has been shown that Chase-ABC
      treatment is able to promote the spread of the viruses, increasing the efficacy
      of the viral treatment. In this paper we develop a mathematical model to
      investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic
      viruses (OV). We show that the model's predictions agree with experimental
      results for a spherical glioma. We then use the model to test various treatment
      options in the heterogeneous microenvironment of the brain. The model predicts
      that separate injections of OV, one into the center of the tumor and another
      outside the tumor will result in better outcome than if the total injection is
      outside the tumor. In particular, the injection of the ECM-degrading enzyme
      (Chase-ABC) on the periphery of the main tumor core need to be administered in an
      optimal strategy in order to infect and eradicate the infiltrating glioma cells
      outside the tumor core in addition to proliferative cells in the bulk of tumor
      core. The model also predicts that the size of tumor satellites and distance
      between the primary tumor and multifocal/satellite lesions may be an important
      factor for the efficacy of the viral therapy with Chase treatment. 

PMID- 25047812
TI  - Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via
      PD-L1 expressed on target keratinocytes.
AB  - Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T
      cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of
      leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell
      mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor
      transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft
      versus-host disease (GVHD). We found that mice expressing OVA on epidermal
      keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after
      transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild
      type OT-I cells. In addition, K14-mOVA * OT-I double Tg (DTg) mice do not develop
      GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1
      KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These
      results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on
      pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14
      mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice
      without the disease do not. These findings reflect the fact that primary
      keratinocytes express PD-L1 when stimulated by interferon-gamma in vitro. When co
      cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited
      enhanced proliferation and activation compared to wild-type OT-I cells. In
      addition, knockdown of 50% PD-L1 expression on the keratinocytes with
      transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our
      data strongly suggest that PD-L1, expressed on activated target keratinocytes
      presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the
      development of mucocutaneous autoimmune diseases.

PMID- 25047813
TI  - Incidental durotomy in lumbar spine surgery--a three-nation survey to evaluate
      its management.
AB  - BACKGROUND: Although it is generally accepted that incidental durotomies (ID)
      should be primarily repaired, the current literature shows no consensus regarding
      the peri- and postoperative management in case of ID during lumbar spine surgery.
      Because ID is a rather frequent complication and may be associated with
      significant disability, we were interested to analyze the current handling of ID
      in three European countries. METHODS: In March 2014, members of the Swiss,
      German, and Austrian neurosurgical and spine societies were asked to complete an
      online questionnaire regarding the management of ID during and after lumbar spine
      surgery. Two, respectively 4 weeks after the first invitation, reminder requests
      were sent to all invitees, who had not already responded at that time. RESULTS:
      There were 175 responses from 397 requests (44.1 %). Responders were
      predominantly neurosurgeons (89.7 %; 10.3 % were orthopedic surgeons), of which
      45.7, 40.0, and 17.8 % work in a non-university hospital, university hospital,
      and private clinic, respectively. As for the perioperative management of ID, 19.4
      % of the responders suggest only bed rest, while, depending on the extent of the
      ID, 84.0 % suggest additional actions, TachoSil/Spongostan with fibrin glue or a
      similar product and single suture repair being the most mentioned. Concerning
      epidural wound drainage in case of ID, 37.2 % desist from placing an epidural
      wound drainage with or without aspiration, 30.9 % place it sometimes, and 33.7 %
      place it regularly, but only without aspiration. Most responders prescribe bed
      rest for 24 (34.9 %) or 48 h (28.0 %), with much fewer prescribing bed rest for
      72 h (6.3 %) and none more than 72 h, and 14.9 % of participants never prescribe
      bed rest. The vast majority of physicians (82.9 %, n = 145) always inform their
      patients after the operation in case of ID. CONCLUSIONS: There is substantial
      heterogeneity in the management of incidental durotomies. The majority of spine
      surgeons today aim at complete/sufficient primary repair of the ID with varying
      recommendations concerning postoperative bed rest. Still, there is a trend
      towards early mobilization if the incidental durotomy has been closed
      completely/sufficiently with no participant favoring bed rest for more than 72 h.

PMID- 25047814
TI  - Structural and biochemical studies of actin in complex with synthetic macrolide
      tail analogues.
AB  - The actin filament-binding and filament-severing activities of the aplyronine,
      kabiramide, and reidispongiolide families of marine macrolides are located within
      the hydrophobic tail region of the molecule. Two synthetic tail analogues of
      aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation
      constants of (285+/-33) and (132+/-13) nM, respectively. The crystal structures
      of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of
      tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our
      studies support the view that filament severing is brought about by specific
      binding of the tail region to the SD1/SD3 cleft on the upper protomer, which
      displaces loop-D from the lower protomer on the same half-filament. With previous
      studies showing that the GC-04 analogue can sever actin filaments, it is argued
      that the shorter complex lifetime of tail analogues with F-actin would make them
      more effective at severing filaments compared with plasma gelsolin. Structure
      based analyses are used to suggest more reactive or targetable forms of GC-04 and
      SF-01, which may serve to boost the capacity of the serum actin scavenging
      system, to generate antibody conjugates against tumor cell antigens, and to
      decrease sputum viscosity in children with cystic fibrosis. 

PMID- 25047815
TI  - Ghrelin receptor modulators: a patent review (2011 - 2014).
AB  - INTRODUCTION: Over the past 3 years, several patents appeared dealing with the
      discovery of compounds able to modulate ghrelin actions: agonists for the
      treatment of cachexia, as diagnostic agents for GH deficiency or for the increase
      in gastrointestinal motility, antagonists and inverse agonists as anorexigenic
      agents for the treatment of obesity and type 2 diabetes. This research has been
      conducted by several pharmaceutical companies and some compounds have entered
      clinical trials, but, to date, compounds acting on the ghrelin receptor do not
      represent clinical options yet. AREAS COVERED: A comprehensive description and
      categorization of patents related to each type of compounds is provided, together
      with data related to these compounds that appeared in the scientific literature.
      EXPERT OPINION: Ghrelin appears to mediate a myriad of actions, and some of these
      appear to be due to unknown mechanisms (a second putative ghrelin receptor,
      putative receptors for unacylated ghrelin); several agonists, antagonists and
      inverse agonists at ghrelin receptor have been developed but their mechanism of
      action into CNS is poorly understood. The therapeutic potential of compounds
      acting on ghrelin receptor is still to be fully assessed, but the results
      obtained to date are encouraging for the successful clinical translation of
      compounds able to treat several pathologies.

PMID- 25047816
TI  - The sensory neurone membrane protein SNMP1 contributes to the sensitivity of a
      pheromone detection system.
AB  - Male moths detect female-released sex pheromones with extraordinary sensitivity.
      The remarkable sensory ability is based on a cooperative interplay of pheromone
      binding proteins in the lymph of hair-like sensilla trichodea and pheromone
      receptors in the dendrites of sensory neurones. Here we examined whether in
      Heliothis virescens the so-called 'sensory neurone membrane protein 1' (SNMP1)
      may contribute to responsiveness to the pheromone component, (Z)-11-hexadecenal
      (Z11-16:Ald). By means of immunohistochemistry and in situ hybridization we
      demonstrated that SNMP1 is in fact present in cells expressing the Z11-16:Ald
      receptor HR13 and the dendrites of sensory neurones. To assess a possible
      function of SNMP1 we monitored the responsiveness of cell lines that expressed
      HR13 alone or the combination SNMP1/HR13 to stimulation with Z11-16:Ald by
      calcium imaging. It was found that SNMP1/HR13 cells were 1000-fold more sensitive
      to pheromone stimulation compared with HR13 cells. In contrast, cells that
      expressed HR13 and the non-neuronal SNMP2-type showed no change in pheromone
      sensitivity. Overall, our reconstitution experiments demonstrate that the
      presence of SNMP1 significantly increases the HR13-based responsiveness of cells
      to Z11-16:Ald, suggesting that SNMP1 also contributes to the response of the
      antennal neurones and thus to the remarkable sensitivity of the pheromone
      detection system. 

PMID- 25047817
TI  - NPPB is a novel candidate biomarker expressed by cancer-associated fibroblasts in
      epithelial ovarian cancer.
AB  - Most solid tumors contain cancer-associated fibroblasts (CAFs) that support
      tumorigenesis and malignant progression. However, the cellular origins of CAFs in
      epithelial ovarian cancers (EOCs) remain poorly understood, and their utility as
      a source of clinical biomarkers for cancer diagnosis has not been explored in
      great depth. Here, we report establishing in vitro and in vivo models of CAFs in
      ovarian cancer development. Normal ovarian fibroblasts and mesenchymal stem cells
      cultured in the presence of EOC cells acquired a CAF-like phenotype, and promoted
      EOC cell migration in vitro. CAFs also promoted ovarian cancer growth in vivo in
      both subcutaneous and intraperitoneal murine xenograft assays. Molecular
      profiling of CAFs identified gene expression signatures that were highly enriched
      for extracellular and secreted proteins. We identified novel candidate CAF
      specific biomarkers for ovarian cancer including NPPB, which was expressed in the
      stroma of 60% primary ovarian cancer tissues (n = 145) but not in the stroma of
      normal ovaries (n = 4). NPPB is a secreted protein that was also elevated in the
      blood of 50% of women with ovarian cancer (n = 8). Taken together, these data
      suggest that the tumor stroma is a novel source of biomarkers, including NPPB,
      that may be of clinical utility for detection of EOC.

PMID- 25047818
TI  - Liver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III
      transgenic mice at cellular and mitochondrial compartment levels.
AB  - BACKGROUND: Hypertriglyceridemia (HTG) is defined as a triglyceride (TG) plasma
      level exceeding 150 mg/dl and is tightly associated with atherosclerosis,
      metabolic syndrome, obesity, diabetes and acute pancreatitis. The present study
      was undertaken to investigate the mitochondrial, sub-mitochondrial and cellular
      proteomic impact of hypertriglyceridemia in the hepatocytes of
      hypertriglyceridemic transgenic mice (overexpressing the human apolipoproteinC
      III). METHODS: Quantitative proteomics (2D-DIGE) analysis was carried out on both
      "low-expressor" (LE) and "high-expressor" (HE) mice, respectively exhibiting
      moderate and severe HTG, to characterize the effect of the TG plasma level on the
      proteomic response. RESULTS: The mitoproteome analysis has revealed a large-scale
      phenomenon in transgenic mice, i.e. a general down-regulation of matricial
      proteins and up-regulation of inner membrane proteins. These data also
      demonstrate that the magnitude of proteomic changes strongly depends on the TG
      plasma level. Our different analyses indicate that, in HE mice, the capacity of
      several metabolic pathways is altered to promote the availability of acetyl-CoA,
      glycerol-3-phosphate, ATP and NADPH for TG de novo biosynthesis. The up
      regulation of several cytosolic ROS detoxifying enzymes has also been observed,
      suggesting that the cytoplasm of HTG mice is subjected to oxidative stress.
      Moreover, our results suggest that iron over-accumulation takes place in the
      cytosol of HE mice hepatocytes and may contribute to enhance oxidative stress and
      to promote cellular proliferation. CONCLUSIONS: These results indicate that the
      metabolic response to HTG in human apolipoprotein C-III overexpressing mice may
      support a high TG production rate and that the cytosol of hepatocytes is
      subjected to an important oxidative stress, probably as a result of FFA over
      accumulation, iron overload and enhanced activity of some ROS-producing catabolic
      enzymes.

PMID- 25047820
TI  - Single-step approach for fabrication of vancomycin-bonded silica monolith as
      chiral stationary phase.
AB  - A vancomycin-bonded silica monolithic column for capillary electrochromatography
      (CEC) was prepared by a single-step in situ sol-gel approach. This sol-gel
      process incorporates a synthetic sol-gel precursor which contains a macrocyclic
      antibiotic, vancomycin, to form a porous silica network inside a fused-silica
      capillary. To avoid degradation of vancomycin during the column fabrication, a
      mild step was adopted into the sol-gel process. The performance of the vancomycin
      chiral stationary phase was investigated by CEC in both the reversed-phase mode
      and the normal-phase mode. The vancomycin chiral stationary phase was optimized
      with respect to vancomycin loading in the reversed-phase mode for chiral
      separation of thalidomide enantiomers. The best efficiency and resolution values
      of 94600plates/m and 5.79, respectively, were achieved. The optimized column was
      further applied to chiral separation of alprenolol enantiomers. A plate height of
      less than 7MUm for the first eluted enantiomer of alprenolol was obtained in an
      aqueous mobile phase at a flow rate of 0.74mm/s. Using enantiomers of seven beta
      blockers and some other basic enantiomers as test analytes, separation
      efficiencies of up to 148100plates/m in the reversed-phase mode and up to
      138100plates/m in the normal-phase mode were achieved. 

PMID- 25047819
TI  - Use of ammonium formate in QuEChERS for high-throughput analysis of pesticides in
      food by fast, low-pressure gas chromatography and liquid chromatography tandem
      mass spectrometry.
AB  - The "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) approach to
      sample preparation is widely applied in pesticide residue analysis, but the use
      of magnesium sulfate and other nonvolatile compounds for salting out in the
      method is not ideal for mass spectrometry. In this study, we developed and
      evaluated three new different versions of the QuEChERS method using more volatile
      salts (ammonium chloride and ammonium formate and acetate buffers) to induce
      phase separation and extraction of 43 representative pesticide analytes of
      different classes. Fast low-pressure gas chromatography tandem mass spectrometry
      (LPGC-MS/MS) and liquid chromatography (LC)-MS/MS were used for analysis. The
      QuEChERS AOAC Official Method 2007.01 was also tested for comparison purposes. Of
      the studied methods, formate buffering using 7.5g of ammonium formate and 15mL of
      5% (v/v) formic acid in acetonitrile for the extraction of 15g of sample (5g for
      wheat grain) provided the best performance and practical considerations. Method
      validation was carried out with and without the use of dispersive solid-phase
      extraction for cleanup, and no significant differences were observed for the
      majority of pesticides. The method was demonstrated in quantitative analysis for
      GC- and LC-amenable pesticides in 4 representative food matrices (apple, lemon,
      lettuce, and wheat grain). With the typical exceptions of certain pH-dependent
      and labile pesticides, 90-110% recoveries and <10% RSD were obtained. Detection
      limits were mostly <5ng/g, which met the general need to determine pesticide
      concentrations as low as 10ng/g for monitoring purposes in food applications. 

PMID- 25047821
TI  - Enantiomeric fraction evaluation of pharmaceuticals in environmental matrices by
      liquid chromatography-tandem mass spectrometry.
AB  - The interest for environmental fate assessment of chiral pharmaceuticals is
      increasing and enantioselective analytical methods are mandatory. This study
      presents an enantioselective analytical method for the quantification of seven
      pairs of enantiomers of pharmaceuticals and a pair of a metabolite. The selected
      chiral pharmaceuticals belong to three different therapeutic classes, namely
      selective serotonin reuptake inhibitors (venlafaxine, fluoxetine and its
      metabolite norfluoxetine), beta-blockers (alprenolol, bisoprolol, metoprolol,
      propranolol) and a beta2-adrenergic agonist (salbutamol). The analytical method
      was based on solid phase extraction followed by liquid chromatography tandem mass
      spectrometry with a triple quadrupole analyser. Briefly, Oasis MCX cartridges
      were used to preconcentrate 250 mL of water samples and the reconstituted
      extracts were analysed with a Chirobiotic V under reversed mode. The effluent of
      a laboratory-scale aerobic granular sludge sequencing batch reactor (AGS-SBR) was
      used to validate the method. Linearity (r(2)>0.99), selectivity and sensitivity
      were achieved in the range of 20-400 ngL(-1) for all enantiomers, except for
      norfluoxetine enantiomers which range covered 30-400 ngL(-1). The method
      detection limits were between 0.65 and 11.5 ngL(-1) and the method quantification
      limits were between 1.98 and 19.7 ngL(-1). The identity of all enantiomers was
      confirmed using two MS/MS transitions and its ion ratios, according to European
      Commission Decision 2002/657/EC. This method was successfully applied to evaluate
      effluents of wastewater treatment plants (WWTP) in Portugal. Venlafaxine and
      fluoxetine were quantified as non-racemic mixtures (enantiomeric fraction ? 0.5).
      The enantioselective validated method was able to monitor chiral pharmaceuticals
      in WWTP effluents and has potential to assess the enantioselective biodegradation
      in bioreactors. Further application in environmental matrices as surface and
      estuarine waters can be exploited.

PMID- 25047822
TI  - Highly sensitive analysis of flavonoids by zwitterionic microemulsion
      electrokinetic chromatography coupled with light-emitting diode-induced
      fluorescence detection.
AB  - A rapid zwitterionic microemulsion electrokinetic chromatography (ZI-MEEKC)
      approach coupled with light-emitting-diode-induced fluorescence (LED-IF, 480nm)
      detection was proposed for the analysis of flavonoids. In the optimization
      process, we systematically investigated the separation conditions, including the
      surfactants, cosurfactants, pH, buffers and fluorescence parameters. It was found
      that the baseline separation of the seven flavonoids was obtained in less than
      5min with a running buffer consisting of 92.9% (v/v) 5mM sodium borate, 0.6%
      (w/v) ZI surfactant, 0.5% (w/v) ethyl acetate and 6.0% (w/v) 1-butanol. High
      sensitivity was obtained by the application of LED-IF detection. The limits of
      detection for seven flavonoids were in the range of 3.30*10(-8) to 2.15*10(
      6)molL(-1) without derivatization. Ultimately, the detection method was
      successfully applied to the analysis of flavonoids in hawthorn plant and food
      products with satisfactory results. 

PMID- 25047823
TI  - Experiment and modeling for the separation of guaifenesin enantiomers using
      simulated moving bed and Varicol units.
AB  - The separation of guaifenesin enantiomers by both simulated moving bed (SMB)
      process and Varicol process was investigated experimentally and theoretically,
      where the columns were packed with cellulose tris 3,5-dimethylphenylcarbamate
      (Chiralcel OD) stationary phase and a mixture of n-hexane and ethanol was used as
      mobile phase. The operation conditions were designed based on the separation
      region with the consideration of mass transfer resistance and axial dispersion,
      and the experiments to separate guaifenesin enantiomers were carried out on
      VARICOL-Micro unit using SMB process with the column configuration of 1/2/2/1 and
      Varicol process with the column configuration of 1/1.5/1.5/1, respectively.
      Single enantiomer with more than 99.0% purity was obtained in both processes with
      the productivity of 0.42 genantiomer/dcm(3) CSP for SMB process and 054
      genantiomer/dcm(3) CSP for Varicol process. These experimental results obtained
      from SMB and Varicol processes were compared with those reported from
      literatures. In addition, according to the numerical simulation, the effects of
      solid-film mass transfer resistance and axial dispersion on the internal profiles
      were discussed, and the effect of column configuration on the separation
      performance of SMB and Varicol processes was analyzed for a few columns system.
      The feasibility and efficiency for the separation of guaifenesin enantiomers by
      SMB and Varicol processes were evaluated.

PMID- 25047824
TI  - Toll-like receptors -4 and -5 in oral and cutaneous squamous cell carcinomas.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) has a worse prognosis than
      cutaneous squamous cell carcinoma (CSCC). Toll-like receptor- 4 (TLR-4) and TLR-5
      are transmembrane proteins that recognize endogenous and microbial agents. Their
      activation has been connected to cancer invasion. OBJECTIVE: The aim was to study
      the expression of TLR-4 and TLR-5 in OSCC and CSCC samples, and the effects of
      TLR-5 ligand flagellin on the proliferation, migration, and invasion of different
      mucocutaneous cell lines in vitro. METHODS: Samples of early-stage tumors (T1
      T2N0M0) from 63 patients with OSCC and CSCC were obtained, in addition to eight
      normal mucosa and skin tissues from healthy subjects. Oral-cavity-derived highly
      aggressive HSC-3, less invasive SAS, and HPV-transformed benign IHGK as well as C
      ha-ras-transformed (HaCat) skin carcinoma II-4 and non-invasive A5 cell lines
      were used. Flagellin-induced mucocutaneous cell lines were compared by using BrdU
      proliferation, scratch migration, and myoma organotypic invasion assays. RESULTS:
      TLR-4 expression was similar in OSCC and CSCC tumors. TLR-5 was more abundant in
      OSCC than in CSCC samples. Flagellin induced the proliferation of SAS, II-4 and
      A5, migration of IHGK, II-4 and A5, and the invasion of II-4 cells. It had no
      effect on HSC-3 cells. CONCLUSIONS: Flagellin, a TLR-5 agonist, induced the
      migration and invasion of less aggressive mucocutaneous cell lines, but it had no
      effect on the most invasive oral carcinoma cells. The more aggressive clinical
      behavior of OSCC compared to CSCC may partially be related to the differences in
      the expression of TLR-5 in these malignancies.

PMID- 25047825
TI  - Rationale and design of the Myocardial Microinjury and Cardiac Remodeling
      Extension Study in the Sodium Lowering in Dialysate trial (Mac-SoLID study).
AB  - BACKGROUND: The Sodium Lowering in Dialysate (SoLID) trial is an ongoing a multi
      center, prospective, randomised, single-blind (assessor), controlled, parallel
      assignment clinical trial, enrolling 96 home and self-care hemodialysis (HD)
      patients from 7 centers in New Zealand. The trial will evaluate the hypothesis
      that lower dialysate [Na+] during HD results in lower left ventricular (LV) mass.
      Since it's inception, observational evidence has suggested increased mortality
      risk with lower dialysate [Na+], possibly due to exacerbation of intra-dialytic
      hypotension and subsequent myocardial micro-injury. The Myocardial Micro-injury
      and Cardiac Remodeling Extension Study in the Sodium Lowering In Dialysate Trial
      (Mac-SoLID study) aims to determine whether lower dialysate [Na+] results in (i)
      increased levels of high-sensitivity Troponin T (hsTnT), a well-established
      marker of intra-dialytic myocardial micro-injury in HD populations, and (ii)
      increased fixed LV segmental wall motion abnormalities, a marker of recurrent
      myocardial stunning and micro-injury, and (iii) detrimental changes in LV
      geometry due to maladaptive homeostatic mechanisms. METHODS/DESIGN: The SoLID
      trial and the Mac-SoLID study are funded by the Health Research Council of New
      Zealand. Key exclusion criteria: patients who dialyse > 3.5 times per week, pre
      dialysis serum sodium <135 mM, and maintenance haemodiafiltration. In addition,
      some medical conditions, treatments or participation in other dialysis trials
      that contraindicate the study intervention or confound its effects, will be
      exclusion criteria. The intervention and control groups will receive dialysate
      sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure
      for the Mac-SOLID study is repeated measures of [hsTnT] at 0, 3, 6, 9, and 12
      months. The secondary outcomes will be assessed using cardiac magnetic resonance
      imaging (MRI), and comprise LV segmental wall motion abnormality scores, LV mass
      to volume ratio and patterns of LV remodeling at 0 and 12 months. DISCUSSION: The
      Mac-SoLID study enhances and complements the SoLID trial. It tests whether
      potential gains in cardiovascular health (reduced LV mass) which low dialysate
      [Na+] is expected to deliver, are counteracted by deterioration in cardiovascular
      health through alternative mechanisms, namely repeated LV stunning and micro
      injury. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry
      number: ACTRN12611000975998.

PMID- 25047826
TI  - A comparison of the effects of transcranial direct current stimulation and
      caffeine on vigilance and cognitive performance during extended wakefulness.
AB  - BACKGROUND: Sleep deprivation from extended duty hours is a common complaint for
      many occupations. Caffeine is one of the most common countermeasures used to
      combat fatigue. However, the benefits of caffeine decline over time and with
      chronic use. OBJECTIVE: Our objective was to evaluate the efficacy of anodal
      transcranial direct current stimulation (tDCS) applied to the pre-frontal cortex
      at 2 mA for 30 min to remediate the effects of sleep deprivation and to compare
      the behavioral effects of tDCS with those of caffeine. METHODS: Three groups of
      10 participants each received either active tDCS with placebo gum, caffeine gum
      with sham tDCS, or sham tDCS with placebo gum during 30 h of extended
      wakefulness. RESULTS: Our results show that tDCS prevented a decrement in
      vigilance and led to better subjective ratings for fatigue, drowsiness, energy,
      and composite mood compared to caffeine and control in sleep-deprived
      individuals. Both the tDCS and caffeine produced similar improvements in
      latencies on a short-term memory task and faster reaction times in a psychomotor
      task when compared to the placebo group. Interestingly, changes in accuracy for
      the tDCS group were not correlated to changes in mood; whereas, there was a
      relationship for the caffeine and sham groups. CONCLUSION: Our data suggest that
      tDCS could be a useful fatigue countermeasure and may be more beneficial than
      caffeine since boosts in performance and mood last several hours.

PMID- 25047827
TI  - Jitter of corticospinal neurons during repetitive transcranial magnetic
      stimulation. Method and possible clinical implications.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the motor
      cortex activates corticospinal neurons mainly through the depolarization of
      cortico-cortical axons belonging to interneurons of superficial layers.
      OBJECTIVE: We used single-fiber electromyography (SFEMG) to estimate the "central
      jitter" of activation latency of interneural pools from one pulse of TMS to
      another. METHODS: We evaluated 10 healthy subjects and one patient with multiple
      sclerosis. By recording SFEMG evoked activity from the left first dorsal
      interosseous (FDI), we first used a standard repetitive electrical 3 Hz
      stimulation of the ulnar nerve at the wrist to calculate the mean consecutive
      difference from at least 10 different potentials. The same procedure was applied
      during 3 Hz repetitive TMS of the contralateral motor cortex. The corticospinal
      monosynaptic connection of the FDI and the selectivity of SFEMG recording
      physiologically justified the subtraction of the "peripheral jitter" from the
      whole cortico-muscular jitter, obtaining an estimation of the actual "central
      jitter." RESULTS: All subjects completed the study. The peripheral jitter was 28
      MUs +/- 6 and the cortico-muscular jitter was 344 MUs +/- 97. The estimated
      central jitter was 343 +/- 97 MUs. In the patient the central jitter was 846 MUs,
      a value more than twice the central jitter in healthy subjects. CONCLUSION:
      Current results demonstrate that the evaluation of the central component of the
      cumulative cortico-muscular latency variability in healthy subjects is feasible
      with a minimally invasive approach. We present and discuss this methodology and
      provide a "proof of concept" of its potential clinical applicability in a patient
      with multiple sclerosis.

PMID- 25047828
TI  - Evaluation of the Microsoft Kinect as a clinical assessment tool of body sway.
AB  - Total body center of mass (TBCM) is a useful kinematic measurement of body sway.
      However, expensive equipment and high technical requirement limit the use of
      motion capture systems in large-scale clinical settings. Center of pressure (CP)
      measurement obtained from force plates cannot accurately represent TBCM during
      large body sway movement. Microsoft Kinect is a rapidly developing, inexpensive,
      and portable posturographic device, which provides objective and quantitative
      measurement of TBCM sway. The purpose of this study was to evaluate Kinect as a
      clinical assessment tool for TBCM sway measurement. The performance of the Kinect
      system was compared with a Vicon motion capture system and a force plate. Ten
      healthy male subjects performed four upright quiet standing tasks: (1) eyes open
      (EOn), (2) eyes closed (ECn), (3) eyes open standing on foam (EOf), and (4) eyes
      closed standing on foam (ECf). Our results revealed that the Kinect system
      produced highly correlated measurement of TBCM sway (mean RMSE=4.38 mm; mean
      CORR=0.94 in Kinect-Vicon comparison), as well as comparable intra-session
      reliability to Vicon. However, the Kinect device consistently overestimated the
      95% CL of sway by about 3mm. This offset could be due to the limited accuracy,
      resolution, and sensitivity of the Kinect sensors. The Kinect device was more
      accurate in the medial-lateral than in the anterior-posterior direction, and
      performed better than the force plate in more challenging balance tasks, such as
      (ECf) with larger TBCM sway. Overall, Kinect is a cost-effective alternative to a
      motion capture and force plate system for clinical assessment of TBCM sway. 

PMID- 25047829
TI  - Complexity of human postural control in subjects with unilateral peripheral
      vestibular hypofunction.
AB  - Complexity is a new measure for identifying the adaptability of a complex system
      to meet possible challenges. For a center of pressure (COP) time series, the
      complexity measure represents the stability of postural control. In this study,
      multiscale entropy (MSE) was used to evaluate the complexity of COP time series
      in six test conditions of sensory organization test (SOT). Complexity index (CI)
      is defined as the summation of entropies with coarse-graining scales 1-20 by MSE.
      A total of 51 subjects belonging to 3 groups - healthy-young, healthy-elderly and
      dizzy - were recruited in this study. The COP signals in both anteroposterior
      (AP) and mediolateral (ML) directions were analyzed respectively. According to
      our results, the CI of AP-direction COP time series is significantly correlated
      to the equilibrium score, which represents the stability of postural control in
      SOT. The AP-direction sway is significant larger than the ML-direction sway,
      particularly in the test conditions with sway-surface. In additions, the CI of AP
      direction COP for the healthy-elderly and dizzy groups are significantly lower
      than those for the healthy young group in the test conditions 1-4. The CI of ML
      direction COP for the healthy-elderly group is significantly lower than those for
      the healthy-young and dizzy groups under test conditions 3 and 6. These results
      show that the complexity loss is a common status of AP-direction COP time series
      for both healthy-elderly and dizzy groups, and the complexity of ML-direction COP
      time series for subjects with unilateral vestibular dysfunction is higher than
      that for the healthy-elderly group specifically under test conditions 3 and 6. 

PMID- 25047830
TI  - Interventional cardiology. A step forwards in comparative effectiveness trial
      design?

PMID- 25047831
TI  - Higher Medicare SNF care utilization by dual-eligible beneficiaries: can Medicaid
      long-term care policies be the answer?
AB  - OBJECTIVE: To examine outcomes associated with dual eligibility (Medicare and
      Medicaid) of patients who are admitted to skilled nursing facility (SNF) care and
      whether differences in outcomes are related to states' Medicaid long-term care
      policies. DATA SOURCES/COLLECTION: We used national Medicare enrollment data and
      claims, and the Minimum Data Set for 890,922 community-residing Medicare fee-for
      service beneficiaries who were discharged to an SNF from a general hospital
      between July 2008 and June 2009. STUDY DESIGN: We estimated the effect of dual
      eligibility on the likelihood of 30-day rehospitalization, becoming a long-stay
      nursing home resident, and 180-day survival while controlling for clinical,
      demographic, socio-economic, residential neighborhood characteristics, and SNF
      fixed effects. We estimated the differences in outcomes by dual eligibility
      status separately for each state and showed their relationship with state
      policies: the average Medicaid payment rate; presence of nursing home certificate
      of-need (CON) laws; and Medicaid home and community-based services (HCBS)
      spending. PRINCIPAL FINDINGS: Dual-eligible patients are equally likely to
      experience 30-day rehospitalization, 12 percentage points more likely to become
      long-stay residents, and 2 percentage points more likely to survive 180 days
      compared to Medicare-only patients. This longer survival can be attributed to
      longer nursing home length of stay. While higher HCBS spending reduces the length
      of-stay gap without affecting the survival gap, presence of CON laws reduces both
      the length-of-stay and survival gaps. CONCLUSIONS: Dual eligibles utilize more
      SNF care and experience higher survival rates than comparable Medicare-only
      patients. Higher HCBS spending may reduce the longer SNF length of stay of dual
      eligibles without increasing mortality and may save money for both Medicare and
      Medicaid.

PMID- 25047832
TI  - Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stability of
      preinitiation complexes, leading to altered gene expression, cell cycle
      progression, and survival of tumor cells.
AB  - Cyclin-dependent kinase 7 (CDK7) activates cell cycle CDKs and is a member of the
      general transcription factor TFIIH. Although there is substantial evidence for an
      active role of CDK7 in mRNA synthesis and associated processes, the degree of its
      influence on global and gene-specific transcription in mammalian species is
      unclear. In the current study, we utilize two novel inhibitors with high
      specificity for CDK7 to demonstrate a restricted but robust impact of CDK7 on
      gene transcription in vivo and in in vitro-reconstituted reactions. We
      distinguish between relative low- and high-dose responses and relate them to
      distinct molecular mechanisms and altered physiological responses. Low inhibitor
      doses cause rapid clearance of paused RNA polymerase II (RNAPII) molecules and
      sufficed to cause genome-wide alterations in gene expression, delays in cell
      cycle progression at both the G1/S and G2/M checkpoints, and diminished survival
      of human tumor cells. Higher doses and prolonged inhibition led to strong
      reductions in RNAPII carboxyl-terminal domain (CTD) phosphorylation, eventual
      activation of the p53 program, and increased cell death. Together, our data
      reason for a quantitative contribution of CDK7 to mRNA synthesis, which is
      critical for cellular homeostasis. 

PMID- 25047833
TI  - Methylation by NSun2 represses the levels and function of microRNA 125b.
AB  - Methylation is a prevalent posttranscriptional modification of RNAs. However,
      whether mammalian microRNAs are methylated is unknown. Here, we show that the
      tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre
      miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation
      by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases
      the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of
      RISC by miR-125, thereby repressing the function of miR-125b in silencing gene
      expression. Our results highlight the impact of miR-125b function via methylation
      by NSun2. 

PMID- 25047834
TI  - Virus meets host microRNA: the destroyer, the booster, the hijacker.
AB  - Virus-host interactions highlight key regulatory steps in the control of gene
      expression. MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein
      production via base pairing with mRNAs. Both DNA and RNA viruses have evolved
      mechanisms to degrade, boost, or hijack cellular miRNAs to benefit the viral life
      cycle. This minireview focuses on recent discoveries in virus-host miRNA
      interactions. 

PMID- 25047835
TI  - Role of the mTORC1 complex in satellite cell activation by RNA-induced
      mitochondrial restoration: dual control of cyclin D1 through microRNAs.
AB  - During myogenesis, satellite stem cells (SCs) are induced to proliferate and
      differentiate to myogenic precursors. The role of energy sensors such as the AMP
      activated protein kinase (AMPK) and the mammalian Target of Rapamycin (mTOR) in
      SC activation is unclear. We previously observed that upregulation of ATP through
      RNA-mediated mitochondrial restoration (MR) accelerates SC activation following
      skeletal muscle injury. We show here that during regeneration, the AMPK-CRTC2
      CREB and Raptor-mTORC-4EBP1 pathways were rapidly activated. The phosho-CRTC2
      CREB complex was essential for myogenesis and activated transcription of the
      critical cell cycle regulator cyclin D1 (Ccnd1). Knockdown (KD) of either mTORC
      or its subunit Raptor delayed SC activation without influencing the
      differentiation program. KD of 4EBP1 had no effect on SC activation but enhanced
      myofiber size. mTORC1 positively regulated Ccnd1 translation but destabilized
      Ccnd1 mRNA. These antithetical effects of mTORC1 were mediated by two microRNAs
      (miRs) targeted to the 3' untranslated region (UTR) of Ccnd1 mRNA: miR-1 was
      downregulated in mTORC-KD muscle, and depletion of miR-1 resulted in increased
      levels of mRNA without any effect on Ccnd1 protein. In contrast, miR-26a was
      upregulated upon mTORC depletion, while anti-miR-26a oligonucleotide specifically
      stimulated Ccnd1 protein expression. Thus, mTORC may act as a timer of satellite
      cell proliferation during myogenesis. 

PMID- 25047836
TI  - A naturally occurring GIP receptor variant undergoes enhanced agonist-induced
      desensitization, which impairs GIP control of adipose insulin sensitivity.
AB  - Glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone secreted
      from gastrointestinal K cells in response to food intake, has an important role
      in the control of whole-body metabolism. GIP signals through activation of the
      GIP receptor (GIPR), a G-protein-coupled receptor (GPCR). Dysregulation of this
      pathway has been implicated in the development of metabolic disease. Here we
      demonstrate that GIPR is constitutively trafficked between the plasma membrane
      and intracellular compartments of both GIP-stimulated and unstimulated
      adipocytes. GIP induces a downregulation of plasma membrane GIPR by slowing GIPR
      recycling without affecting internalization kinetics. This transient reduction in
      the expression of GIPR in the plasma membrane correlates with desensitization to
      the effects of GIP. A naturally occurring variant of GIPR (E354Q) associated with
      an increased incidence of insulin resistance, type 2 diabetes, and cardiovascular
      disease in humans responds to GIP stimulation with an exaggerated downregulation
      from the plasma membrane and a delayed recovery of GIP sensitivity following
      cessation of GIP stimulation. This perturbation in the desensitization
      resensitization cycle of the GIPR variant, revealed in studies of cultured
      adipocytes, may contribute to the link of the E354Q variant to metabolic disease.

PMID- 25047837
TI  - ISL1 regulates peroxisome proliferator-activated receptor gamma activation and
      early adipogenesis via bone morphogenetic protein 4-dependent and -independent
      mechanisms.
AB  - While adipogenesis is controlled by a cascade of transcription factors, the
      global gene expression profiles in the early phase of adipogenesis are not well
      defined. Using microarray analysis of gene expression in 3T3-L1 cells, we have
      identified evidence for the activity of 2,568 genes during the early phase of
      adipocyte differentiation. One of these, the ISL1 gene, was of interest since its
      expression was markedly upregulated 1 h after initiation of differentiation, with
      a subsequent rapid decline. Overexpression of ISL1 at early times during
      adipocyte differentiation but not at later times was found to profoundly inhibit
      differentiation. This was accompanied by moderate downregulation of peroxisome
      proliferator-activated receptor gamma (PPARgamma) levels, substantial
      downregulation of PPARgamma downstream genes, and downregulation of bone
      morphogenetic protein 4 (BMP4) levels in preadipocytes. Readdition of BMP4
      overcame the inhibitory effect of ISL1 on the expression of PPARgamma but not
      aP2, a gene downstream of PPARgamma, and BMP4 also partially rescued ISL1
      inhibition of adipogenesis, an effect which is additive with rosiglitazone. These
      results suggest that ISL1 is intimately involved in early regulation of
      adipogenesis, modulating PPARgamma expression and activity via BMP4-dependent and
      -independent mechanisms. Our time course gene expression survey sets the stage
      for further studies to explore other early and immediate regulators. 

PMID- 25047838
TI  - Uncovering the PI3Ksome: phosphoinositide 3-kinases and counteracting PTEN form a
      signaling complex with intrinsic regulatory properties.
AB  - Production of the phosphoinositide lipid phosphatidylinositol
      (3,4,5)trisphosphate [PI(3,4,5)P3, or PIP3] by class I phosphoinositide 3-kinases
      (PI3Ks) is a major signaling mechanism whose deregulation contributes to serious
      diseases, including cancer. New findings suggest that tyrosine kinase receptor
      engagement results in the assembly of hetero-oligomeric PI3K complexes in which
      PI3Kalpha first activates PI3Kbeta, and PI3K catalytic activity then promotes
      recruitment and activation of the PIP3-removing tumor suppressor PTEN. Thus, PIP3
      production is fine-tuned through formation of an intrinsically regulated
      "PI3Ksome." 

PMID- 25047839
TI  - Plk1 phosphorylation of PTEN causes a tumor-promoting metabolic state.
AB  - One outcome of activation of the phosphatidylinositol 3-kinase (PI3K) pathway is
      increased aerobic glycolysis, but the upstream signaling events that regulate the
      PI3K pathway, and thus the Warburg effect, are elusive. Increasing evidence
      suggests that Plk1, a cell cycle regulator, is also involved in cellular events
      in addition to mitosis. To test whether Plk1 contributes to activation of the
      PI3K pathway, and thus aerobic glycolysis, we examined potential targets of Plk1
      and identified PTEN as a Plk1 substrate. We hypothesize that Plk1 phosphorylation
      of PTEN leads to its inactivation, activation of the PI3K pathway, and the
      Warburg effect. Our data show that overexpression of Plk1 leads to activation of
      the PI3K pathway and enhanced aerobic glycolysis. In contrast, inhibition of Plk1
      causes markedly reduced glucose metabolism in mice. Mechanistically, we show that
      Plk1 phosphorylation of PTEN and Nedd4-1, an E3 ubiquitin ligase of PTEN, results
      in PTEN inactivation. Finally, we show that Plk1 phosphorylation of PTEN promotes
      tumorigenesis in both its phosphatase-dependent and -independent pathways,
      revealing potentially new drug targets to arrest tumor cell growth. 

PMID- 25047840
TI  - Polycomb repressive complex 2 and H3K27me3 cooperate with H3K9 methylation to
      maintain heterochromatin protein 1alpha at chromatin.
AB  - Methylation of histone H3 on lysine 9 or 27 is crucial for heterochromatin
      formation. Previously considered hallmarks of, respectively, constitutive and
      facultative heterochromatin, recent evidence has accumulated in favor of
      coexistence of these two marks and their cooperation in gene silencing
      maintenance. H3K9me2/3 ensures anchorage at chromatin of heterochromatin protein
      1alpha (HP1alpha), a main component of heterochromatin. HP1alpha chromoshadow
      domain, involved in dimerization and interaction with partners, has additional
      but still unclear roles in HP1alpha recruitment to chromatin. Because of
      previously suggested links between polycomb repressive complex 2 (PRC2), which
      catalyzes H3K27 methylation, and HP1alpha, we tested whether PRC2 may regulate
      HP1alpha abundance at chromatin. We found that the EZH2 and SUZ12 subunits of
      PRC2 are required for HP1alpha stability, as knockdown of either protein led to
      HP1alpha degradation. Similar results were obtained upon overexpression of
      H3K27me2/3 demethylases. We further showed that binding of HP1alpha/beta/gamma to
      H3K9me3 peptides is greatly increased in the presence of H3K27me3, and this is
      dependent on PRC2. These data fit with recent proteomic studies identifying PRC2
      as an indirect H3K9me3 binder in mouse tissues and suggest the existence of a
      cooperative mechanism of HP1alpha anchorage at chromatin involving H3 methylation
      on both K9 and K27 residues. 

PMID- 25047841
TI  - Dosimetric characterization of the (60)Co BEBIG Co0.A86 high dose rate
      brachytherapy source using PENELOPE.
AB  - (60)Co sources are being used as an alternative to (192)Ir sources in high dose
      rate brachytherapy treatments. In a recent document from AAPM and ESTRO, a
      consensus dataset for the (60)Co BEBIG (model Co0.A86) high dose rate source was
      prepared by using results taken from different publications due to discrepancies
      observed among them. The aim of the present work is to provide a new calculation
      of the dosimetric characteristics of that (60)Co source according to the
      recommendations of the AAPM and ESTRO report. Radial dose function, anisotropy
      function, air-kerma strength, dose rate constant and absorbed dose rate in water
      have been calculated and compared to the results of previous works. Simulations
      using the two different geometries considered by other authors have been carried
      out and the effect of the cable density and length has been studied. 

PMID- 25047842
TI  - Mycobacterial gene cuvA is required for optimal nutrient utilization and
      virulence.
AB  - To persist and cause disease in the host, Mycobacterium tuberculosis must adapt
      to its environment during infection. Adaptations include changes in nutrient
      utilization and alterations in growth rate. M. tuberculosis Rv1422 is a conserved
      gene of unknown function that was found in a genetic screen to interact with the
      mce4 cholesterol uptake locus. The Rv1422 protein is phosphorylated by the M.
      tuberculosis Ser/Thr kinases PknA and PknB, which regulate cell growth and cell
      wall synthesis. Bacillus subtilis strains lacking the Rv1422 homologue yvcK grow
      poorly on several carbon sources, and yvcK is required for proper localization of
      peptidoglycan synthesis. Here we show that Mycobacterium smegmatis and M.
      tuberculosis strains lacking Rv1422 have growth defects in minimal medium
      containing limiting amounts of several different carbon sources. These strains
      also have morphological abnormalities, including shortened and bulging cells,
      suggesting a cell wall defect. In both mycobacterial species, the Rv1422 protein
      localizes uniquely to the growing cell pole, the site of peptidoglycan synthesis
      in mycobacteria. An M. tuberculosis DeltaRv1422 strain is markedly attenuated for
      virulence in a mouse infection model, where it elicits decreased inflammation in
      the lungs and shows impaired bacterial persistence. These findings led us to name
      this gene cuvA (carbon utilization and virulence protein A) and to suggest a
      model in which deletion of cuvA leads to changes in nutrient uptake and/or
      metabolism that affect cell wall structure, morphology, and virulence. Its role
      in virulence suggests that CuvA may be a useful target for novel inhibitors of M.
      tuberculosis during infection. 

PMID- 25047843
TI  - Porphyromonas gingivalis-induced reactive oxygen species activate JAK2 and
      regulate production of inflammatory cytokines through c-Jun.
AB  - Pathogen-induced reactive oxygen species (ROS) play a crucial role in host innate
      immune responses through regulating the quality and quantity of inflammatory
      mediators. However, the underlying molecular mechanisms of this effect have yet
      to be clarified. In this study, we examined the mechanism of action of ROS
      stimulated by Porphyromonas gingivalis in gingival epithelial cells. P.
      gingivalis induced the rapid production of ROS, which lead to the phosphorylation
      of JAK2 and increased levels of secreted proinflammatory cytokines interleukin-6
      (IL-6) and IL-1beta. Neutralization of ROS by N-acetyl-l-cysteine (NAC) abrogated
      the phosphorylation of JAK2 and suppressed the production of IL-6 and IL-1beta.
      ROS-mediated phosphorylation of JAK2 induced the phosphoactivation of c-Jun amino
      terminal protein kinase (JNK) and the downstream transcriptional regulator c-Jun.
      Inhibition of JAK2, either pharmacologically or by small interfering RNA (siRNA),
      reduced both the phosphorylation of these molecules and the production of
      proinflammatory cytokines in response to P. gingivalis. Furthermore,
      pharmacological inhibition or siRNA-mediated gene silencing of JNK or c-Jun
      mimicked the effect of JAK2 inhibition to suppress P. gingivalis-induced IL-6 and
      IL-1beta levels. The results show that ROS-mediated activation of JAK2 is
      required for P. gingivalis-induced inflammatory cytokine production and that the
      JNK/c-Jun signaling axis is involved in the ROS-dependent regulation of IL-1beta
      and IL-6 production. 

PMID- 25047844
TI  - Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar
      bone resorption via differential regulation of Toll-like receptor 2 (TLR2) and
      TLR4.
AB  - Toll-like receptors (TLRs) play a key role in the innate immune responses to
      periodontal pathogens in periodontal disease. The present study was performed to
      determine the roles of TLR2 and TLR4 signaling in alveolar bone resorption, using
      a Porphyromonas gingivalis-associated ligature-induced periodontitis model in
      mice. Wild-type (WT), Tlr2(-/-), and Tlr4(-/-) mice (8 to 10 weeks old) in the
      C57/BL6 background were used. Silk ligatures were applied to the maxillary second
      molars in the presence or absence of live P. gingivalis infection. Ligatures were
      removed from the second molars on day 14, and mice were kept for another 2 weeks
      before sacrifice for final analysis (day 28). On day 14, there were no
      differences in alveolar bone resorption and gingival RANKL expression between
      mice treated with ligation plus P. gingivalis infection and mice treated with
      ligation alone. Gingival interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNF-alpha) expression was increased, whereas IL-10 expression was
      decreased in WT and Tlr2(-/-) mice but not in Tlr4(-/-) mice. On day 28, WT and
      Tlr4(-/-) mice treated with ligation plus P. gingivalis infection showed
      significantly increased bone loss and gingival RANKL expression compared to those
      treated with ligation alone, whereas such an increase was diminished in Tlr2(-/-)
      mice. Gingival TNF-alpha upregulation and IL-10 downregulation were observed only
      in WT and Tlr4(-/-) mice, not in Tlr2(-/-) mice. In all mice, bone resorption
      induced by ligation plus P. gingivalis infection was antagonized by local anti
      RANKL antibody administration. This study suggests that P. gingivalis exacerbates
      ligature-induced, RANKL-dependent periodontal bone resorption via differential
      regulation of TLR2 and TLR4 signaling. 

PMID- 25047845
TI  - Distinct susceptibilities of corneal Pseudomonas aeruginosa clinical isolates to
      neutrophil extracellular trap-mediated immunity.
AB  - Ocular bacterial keratitis, often associated with Pseudomonas aeruginosa
      bacterial infection, commonly occurs in contact lens wearers and may lead to
      vision impairment. In this study, we analyzed the contribution of neutrophil
      extracellular traps (NETs) to the mediation of protection during ocular
      keratitis. Both invasive and cytotoxic P. aeruginosa clinical isolates induced
      NET release by neutrophils. NETs carried the characteristic histone proteins,
      elastase, lysozyme, myeloperoxidase, and metabolic enzymes. While the invasive P.
      aeruginosa strains PAO1 (serogroup O5) and 6294 (serogroup O6) were trapped by
      NETs, the cytotoxic P. aeruginosa strains 6077, 6206 (serogroup O11), and PA14
      (serogroup 010) were less sensitive to NET capture. The mechanism of escape by
      the cytotoxic strains from adhesion to NETs involved the shedding of outer
      membrane vesicles (OMVs) that outcompeted the cytotoxic P. aeruginosa strains for
      NET binding. When ocular infection was caused by an invasive strain in vivo, NETs
      were released at the ocular surface to capture bacteria, limiting their spread.
      Treatment with MNase I had a dose-dependent effect, with low doses of MNase
      speeding up bacterial clearance and high doses of MNase having toxic
      consequences. Cumulatively, our data suggest that NET-mediated immunity is a two
      step process. Initially, pathogens attach to NET fragments; subsequently, upon
      nuclease activity, active serine proteases, which proteolytically degrade NET
      associated proteins and promote DNase activity, are released. Therefore, a
      balance between NET production and NET degradation is needed to achieve maximal
      NET immunity. 

PMID- 25047846
TI  - Staphylococcal Esx proteins modulate apoptosis and release of intracellular
      Staphylococcus aureus during infection in epithelial cells.
AB  - The opportunistic pathogen Staphylococcus aureus is one of the major causes of
      health care-associated infections. S. aureus is primarily an extracellular
      pathogen, but it was recently reported to invade and replicate in several host
      cell types. The ability of S. aureus to persist within cells has been implicated
      in resistance to antimicrobials and recurrent infections. However, few
      staphylococcal proteins that mediate intracellular survival have been identified.
      Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system
      (Ess), are important during intracellular S. aureus infection. The Esx proteins
      are required for staphylococcal virulence, but their functions during infection
      are unclear. While isogenic S. aureus esxA and esxB mutants were not defective
      for epithelial cell invasion in vitro, a significant increase in early/late
      apoptosis was observed in esxA mutant-infected cells compared to wild-type
      infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the
      protein also resulted in a significant increase of epithelial cell apoptosis.
      Furthermore, cells transfected with esxA showed an increased protection from
      apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced
      increased apoptosis but, remarkably, was unable to escape from cells as
      efficiently as the single mutants or the wild type. Thus, using in vitro models
      of intracellular staphylococcal infection, we demonstrate that EsxA interferes
      with host cell apoptotic pathways and, together with EsxB, mediates the release
      of S. aureus from the host cell. 

PMID- 25047847
TI  - Ehrlichia chaffeensis exploits host SUMOylation pathways to mediate effector-host
      interactions and promote intracellular survival.
AB  - Ehrlichia chaffeensis is an obligately intracellular Gram-negative bacterium that
      selectively infects mononuclear phagocytes. We recently reported that E.
      chaffeensis utilizes a type 1 secretion (T1S) system to export tandem repeat
      protein (TRP) effectors and demonstrated that these effectors interact with a
      functionally diverse array of host proteins. By way of these interactions, TRP
      effectors modulate host cell functions; however, the molecular basis of these
      interactions and their roles in ehrlichial pathobiology are not well defined. In
      this study, we describe the first bacterial protein posttranslational
      modification (PTM) by the small ubiquitin-like modifier (SUMO). The E.
      chaffeensis T1S effector TRP120 is conjugated to SUMO at a carboxy-terminal
      canonical consensus SUMO conjugation motif in vitro and in human cells. In human
      cells, TRP120 was selectively conjugated with SUMO2/3 isoforms. Disruption of
      TRP120 SUMOylation perturbed interactions with known host proteins, through
      predicted SUMO interaction motif-dependent and -independent mechanisms. E.
      chaffeensis infection did not result in dramatic changes in the global host
      SUMOylated protein profile, but a robust colocalization of predominately SUMO1
      with ehrlichial inclusions was observed. Inhibiting the SUMO pathway with a small
      molecule inhibitor had a significant impact on E. chaffeensis replication and
      recruitment of the TRP120-interacting protein polycomb group ring finger protein
      5 (PCGF5) to the inclusion, indicating that the SUMO pathway is critical for
      intracellular survival. This study reveals the novel exploitation of the SUMO
      pathway by Ehrlichia, which facilitates effector-eukaryote interactions necessary
      to usurp the host and create a permissive intracellular niche. 

PMID- 25047848
TI  - The HtrA-like protease CD3284 modulates virulence of Clostridium difficile.
AB  - In the past decade, Clostridium difficile has emerged as an important gut
      pathogen. Symptoms of C. difficile infection range from mild diarrhea to
      pseudomembranous colitis. Besides the two main virulence factors toxin A and
      toxin B, other virulence factors are likely to play a role in the pathogenesis of
      the disease. In other Gram-positive and Gram-negative pathogenic bacteria,
      conserved high-temperature requirement A (HtrA)-like proteases have been shown to
      have a role in protein homeostasis and quality control. This affects the
      functionality of virulence factors and the resistance of bacteria to (host
      induced) environmental stresses. We found that the C. difficile 630 genome
      encodes a single HtrA-like protease (CD3284; HtrA) and have analyzed its role in
      vivo and in vitro through the creation of an isogenic ClosTron-based htrA mutant
      of C. difficile strain 630Deltaerm (wild type). In contrast to the attenuated
      phenotype seen with htrA deletion in other pathogens, this mutant showed enhanced
      virulence in the Golden Syrian hamster model of acute C. difficile infection.
      Microarray data analysis showed a pleiotropic effect of htrA on the transcriptome
      of C. difficile, including upregulation of the toxin A gene. In addition, the
      htrA mutant showed reduced spore formation and adherence to colonic cells.
      Together, our data show that htrA can modulate virulence in C. difficile. 

PMID- 25047849
TI  - Porphyromonas gingivalis lipopolysaccharide weakly activates M1 and M2 polarized
      mouse macrophages but induces inflammatory cytokines.
AB  - Porphyromonas gingivalis is associated with chronic periodontitis, an
      inflammatory disease of the tooth's supporting tissues. Macrophages are important
      in chronic inflammatory conditions, infiltrating tissue and becoming polarized to
      an M1 or M2 phenotype. As responses to stimuli differ between these phenotypes,
      we investigated the effect of P. gingivalis lipopolysaccharide (LPS) on M1 and M2
      macrophages. M1 and M2 polarized macrophages were produced from murine bone
      marrow macrophages (BMMphi) primed with gamma interferon (IFN-gamma) or
      interleukin-4 (IL-4), respectively, and incubated with a low or high dose of P.
      gingivalis LPS or control TLR2 and TLR4 ligands. In M1-Mphi, the high dose of P.
      gingivalis LPS (10 MUg/ml) significantly increased the expression of CD40, CD86,
      inducible nitric oxide synthase, and nitric oxide secretion. The low dose of P.
      gingivalis LPS (10 ng/ml) did not induce costimulatory or antibacterial molecules
      but did increase the secretion of IL-1alpha, IL-6, IL-12p40, IL-12p70, and tumor
      necrosis factor alpha (TNF-alpha). P. gingivalis LPS marginally increased the
      expression of CD206 and YM-1, but it did enhance arginase expression by M2-Mphi.
      Furthermore, the secretion of the chemokines KC, RANTES, eotaxin, and MCP-1 from
      M1, M2, and nonpolarized Mphi was enhanced by P. gingivalis LPS. TLR2/4 knockout
      macrophages combined with the TLR activation assays indicated that TLR2 is the
      main activating receptor for P. gingivalis LPS and whole cells. In conclusion,
      although P. gingivalis LPS weakly activated M1-Mphi or M2-Mphi compared to
      control TLR ligands, it induced the secretion of inflammatory cytokines,
      particularly TNF-alpha from M1-Mphi and IL-10 from M2-Mphi, as well as
      chemotactic chemokines from polarized macrophages. 

PMID- 25047850
TI  - Nitric oxide levels regulate the immune response of Drosophila melanogaster
      reference laboratory strains to bacterial infections.
AB  - Studies on the innate immune response against microbial infections in Drosophila
      melanogaster involve mutant strains and their reference strains that act as
      experimental controls. We used five standard D. melanogaster laboratory reference
      strains (Oregon R, w1118, Canton-S, Cinnabar Brown, and Yellow White [YW]) and
      investigated their response against two pathogenic bacteria (Photorhabdus
      luminescens and Enterococcus faecalis) and two nonpathogenic bacteria
      (Escherichia coli and Micrococcus luteus). We detected high sensitivity among YW
      flies to bacterial infections and increased bacterial growth compared to the
      other strains. We also found variation in the transcription of certain
      antimicrobial peptide genes among strains, with Oregon and YW infected flies
      showing the highest and lowest gene transcription levels in most cases. We show
      that Oregon and w1118 flies possess more circulating hemocytes and higher levels
      of phenoloxidase activity than the other strains upon infection with the
      nonpathogenic bacteria. We further observed reduced fat accumulation in YW flies
      infected with the pathogenic bacteria, which suggests a possible decline in
      physiological condition. Finally, we found that nitrite levels are significantly
      lower in infected and uninfected YW flies compared to w1118 flies and that nitric
      oxide synthase mutant flies in YW background are more susceptible to bacterial
      infection compared to mutants in w1118 background. Therefore, increased
      sensitivity of YW flies to bacterial infections can be partly attributed to lower
      levels of nitric oxide. Such studies will significantly contribute toward a
      better understanding of the genetic variation between D. melanogaster reference
      strains. 

PMID- 25047851
TI  - Fat metaplasia and backfill are key intermediaries in the development of
      sacroiliac joint ankylosis in patients with ankylosing spondylitis.
AB  - OBJECTIVE: Fat metaplasia in bone marrow on T1-weighted magnetic resonance
      imaging (MRI) scans may develop after resolution of inflammation in patients with
      ankylosing spondylitis (AS) and may predict new bone formation in the spine.
      Similar tissue, termed backfill, may also fill areas of excavated bone in the
      sacroiliac (SI) joints and may reflect resolution of inflammation and tissue
      repair at sites of erosions. The purpose of this study was to test our hypothesis
      that SI joint ankylosis develops following repair of erosions and that tissue
      characterized by fat metaplasia is a key intermediary step in this pathway.
      METHODS: We used the Spondyloarthritis Research Consortium of Canada (SPARCC) SI
      structural lesion score (SSS) method to assess fat metaplasia, erosions,
      backfill, and ankylosis on MRIs of the SI joints in 147 patients with AS
      monitored for 2 years. Univariate and multivariate regression analyses focused
      first on identifying significant MRI predictors of new backfill and fat
      metaplasia. We then assessed the role of backfill and fat metaplasia in the
      development of new ankylosis. All analyses were adjusted for demographic
      features, treatment, and baseline and 2-year change in SSS values for parameters
      of inflammation and MRI structural lesions. RESULTS: Resolution of inflammation
      and reduction of erosions were each independently associated with the development
      of new backfill and fat metaplasia at 2 years on multivariate analyses.
      Multivariate regression analysis that included demographic features, baseline and
      2-year change in parameters of inflammation and MRI structural lesion showed that
      reduction in erosions (P = 0.0005) and increase in fat metaplasia (P = 0.002) at
      2 years was each independently associated with the development of new ankylosis.
      CONCLUSION: Our data support a disease model whereby ankylosis develops following
      repair of erosions, and fat metaplasia and backfill are key intermediary steps in
      this pathway.

PMID- 25047852
TI  - Association between physical activity advice only or structured exercise training
      with blood pressure levels in patients with type 2 diabetes: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Diabetes is associated with marked cardiovascular morbidity and
      mortality. However, the association between different types of exercise training
      and blood pressure (BP) changes is not fully clear in type 2 diabetes. OBJECTIVE:
      The aim of this systematic review and meta-analysis of randomized controlled
      clinical trials (RCTs) was to determine the effects of structured exercise
      training (aerobic [AER], resistance [RES], or combined [COMB]) and physical
      activity (PA) advice only on BP changes in patients with type 2 diabetes.
      METHODS: Searches in five electronic databases were conducted to retrieve studies
      published from 1980 to 2013. Eligible studies were RCTs consisting of structured
      exercise training or PA advice versus no intervention in patients with type 2
      diabetes. We used random effect models to derive weighted mean differences (WMDs)
      of exercises on absolute changes in systolic BP (SBP) and diastolic BP (DBP).
      RESULTS: A total of 30 RCTs of structured training (2,217 patients) and 21 of PA
      advice (7,323 patients) were included. Data were extracted independently in
      duplicate. Structured exercise was associated with reductions in SBP (WMD -4.22
      mmHg; 95% confidence interval [CI] -5.89 to -2.56) and DBP (WMD -2.07 mmHg; 95%
      CI -3.03 to -1.11) versus controls. In structured exercise interventions, AER and
      RES were associated with declines in BP, and COMB was not associated with BP
      changes. However, in sensitivity analysis, a high-intensity protocol within COMB
      was associated with declines in SBP (WMD -3.30 mmHg; 95% CI -4.71 to -1.89).
      Structured exercise longer than 150 min/week was associated with greater BP
      reductions. PA advice only was associated with reduction in SBP (WMD -2.97 mmHg;
      95% CI -4.52 to -1.43) and DBP (WMD -1.41 mmHg; 95% CI -1.94 to -0.88) versus
      controls. CONCLUSIONS: AER, RES, and high-intensity combined training are
      associated with BP reduction in patients with type 2 diabetes, especially in
      exercise programs lasting more than 150 min/week. PA advice only is also
      associated with lower BP levels.

PMID- 25047853
TI  - The effect of inter-set rest intervals on resistance exercise-induced muscle
      hypertrophy.
AB  - Due to a scarcity of longitudinal trials directly measuring changes in muscle
      girth, previous recommendations for inter-set rest intervals in resistance
      training programs designed to stimulate muscular hypertrophy were primarily based
      on the post-exercise endocrinological response and other mechanisms theoretically
      related to muscle growth. New research regarding the effects of inter-set rest
      interval manipulation on resistance training-induced muscular hypertrophy is
      reviewed here to evaluate current practices and provide directions for future
      research. Of the studies measuring long-term muscle hypertrophy in groups
      employing different rest intervals, none have found superior muscle growth in the
      shorter compared with the longer rest interval group and one study has found the
      opposite. Rest intervals less than 1 minute can result in acute increases in
      serum growth hormone levels and these rest intervals also decrease the serum
      testosterone to cortisol ratio. Long-term adaptations may abate the post-exercise
      endocrinological response and the relationship between the transient change in
      hormonal production and chronic muscular hypertrophy is highly contentious and
      appears to be weak. The relationship between the rest interval-mediated effect on
      immune system response, muscle damage, metabolic stress, or energy production
      capacity and muscle hypertrophy is still ambiguous and largely theoretical. In
      conclusion, the literature does not support the hypothesis that training for
      muscle hypertrophy requires shorter rest intervals than training for strength
      development or that predetermined rest intervals are preferable to auto-regulated
      rest periods in this regard. 

PMID- 25047856
TI  - Re: Association of elevated fasting glucose with lower patency and increased
      major adverse limb events among patients with diabetes undergoing infrapopliteal
      balloon angioplasty.

PMID- 25047855
TI  - Collateral vessel number, plaque burden, and functional decline in peripheral
      artery disease.
AB  - Associations of collateral vessels and lower extremity plaque with functional
      decline are unknown. Among people with peripheral artery disease (PAD), we
      determined whether greater superficial femoral artery (SFA) plaque burden
      combined with fewer lower extremity collateral vessels was associated with faster
      functional decline, compared to less plaque and/or more numerous collateral
      vessels. A total of 226 participants with ankle-brachial index (ABI) <1.00
      underwent magnetic resonance imaging of lower extremity collateral vessels and
      cross-sectional imaging of the proximal SFA. Participants were categorized as
      follows: Group 1 (best), maximum plaque area < median and collateral vessel
      number >=6 (median); Group 2, maximum plaque area < median and collateral vessel
      number <6; Group 3, maximum plaque area > median and collateral vessel number
      >=6; Group 4 (worst), maximum plaque area > median and collateral vessel number
      <6. Functional measures were performed at baseline and annually for 2 years.
      Analyses adjust for age, sex, race, comorbidities, and other confounders. Annual
      changes in usual-paced walking velocity were: Group 1, +0.01 m/s; Group 2, -0.02
      m/s; Group 3, -0.01 m/s; Group 4, -0.05 m/s (p-trend=0.008). Group 4 had greater
      decline than Group 1 (p<0.001), Group 2 (p=0.029), and Group 3 (p=0.010). Similar
      trends were observed for fastest-paced 4-meter walking velocity (p-trend=0.018).
      Results were not substantially changed when analyses were repeated with
      additional adjustment for ABI. However, there were no associations of SFA plaque
      burden and collateral vessel number with decline in 6-minute walk. In summary, a
      larger SFA plaque burden combined with fewer collateral vessels is associated
      with a faster decline in usual and fastest-paced walking velocity in PAD.

PMID- 25047854
TI  - Fatigue and pacing in high-intensity intermittent team sport: an update.
AB  - With the advancements in player tracking technology, the topic of fatigue and
      pacing in team sport has become increasingly popular in recent years. Initially
      based upon a pre-conceived pacing schema, a central metabolic control system is
      proposed to guide the movement of players during team sport matches, which can be
      consciously modified based on afferent signals from the various physiological
      systems and in response to environmental cues. On the basis of this theory,
      coupled with the collective findings from motion-analysis research, we sought to
      define the different pacing strategies employed by team sport players. Whole
      match players adopt a 'slow-positive' pacing profile (gradual decline in total
      running intensity), which appears to be global across the different team sports.
      High-intensity movement also declines in a 'slow-positive' manner across most
      team sport matches. The duration of the exercise bout appears to be important for
      the selected exercise intensity, with the first introduction to a match as a
      substitute or interchange player resulting in a 'one bout, all out' strategy. In
      a limited interchange environment, a second introduction to the match results in
      a 'second-bout reserve' strategy; otherwise, the 'one bout, all out' strategy is
      likely to be adopted. These pacing profiles are proposed to reflect the presence
      of a central regulator that controls the movement intensity of the player to
      optimize performance, as well as avoiding the harmful failure of any
      physiological system. The presence of 'temporary fatigue' reflects this process,
      whereby exercise intensity is consciously modulated from within the framework of
      a global pacing schema. 

PMID- 25047857
TI  - SVM Annual Meeting - June 2014 La Jolla, California, USA.

PMID- 25047858
TI  - Vascular Disease Patient Information Page: The post-thrombotic syndrome.

PMID- 25047859
TI  - Highlights of the SVM 25th Anniversary and Scientific Sessions.

PMID- 25047860
TI  - Corrigendum to The role of novel anticoagulants in the management of venous
      thromboembolism.
AB  - The authors (Nedaa Skeik, Caleb J Murphy and Brandon R Porten) would like to
      highlight the following corrections to Table 2 in their review article, DOI:
      10.1177/1358863X14534309. The review was printed in Vascular Medicine 2014; 19:
      205-214. The authors would like to apologize for any inconvenience these changes
      will cause.

PMID- 25047861
TI  - Genomic data integration for ecological and evolutionary traits in non-model
      organisms.
AB  - Why is it needed to develop system biology initiatives such as ENCODE on non
      model organisms? 

PMID- 25047862
TI  - Venous thromboembolism after total joint arthroplasty: results from a Japanese
      multicenter cohort study.
AB  - INTRODUCTION: Real-world evidence of the effectiveness of pharmacological
      thromboprophylaxis for venous thromboembolism (VTE) is limited. Our objective was
      to assess the effectiveness and safety of thromboprophylactic regimens in
      Japanese patients undergoing joint replacement in a real-world setting. METHOD:
      Overall, 1,294 patients (1,073 females and 221 males) who underwent total knee
      arthroplasty (TKA) and 868 patients (740 females and 128 males) who underwent
      total hip arthroplasty (THA) in 34 Japanese national hospital organization (NHO)
      hospitals were enrolled. The primary efficacy outcome was the incidence of deep
      vein thrombosis (DVT) detected by mandatory bilateral ultrasonography up to post
      operative day (POD) 10 and pulmonary embolism (PE) up to POD28. The main safety
      outcomes were bleeding (major or minor) and death from any cause up to POD28.
      RESULTS: Patients undergoing TKA (n = 1,294) received fondaparinux (n = 360),
      enoxaparin (n = 223), unfractionated heparin (n = 72), anti-platelet agents (n =
      45), or no medication (n = 594). Patients undergoing THA (n = 868) received
      fondaparinux (n = 261), enoxaparin (n = 148), unfractionated heparin (n = 32),
      anti-platelet agents (n = 44), or no medication (n = 383). The incidence rates of
      sonographically diagnosed DVTs up to POD10 were 24.3% in patients undergoing TKA
      and 12.6% in patients undergoing THA, and the incidence rates of major bleeding
      up to POD28 were 1.2% and 2.3%, respectively. Neither fatal bleeding nor fatal
      pulmonary embolism occurred. Significant risk factors for postoperative VTE
      identified by multivariate analysis included gender (female) in both TKA and THA
      groups and use of a foot pump in the TKA group. Only prophylaxis with
      fondaparinux reduced the occurrence of VTE significantly in both groups.
      Propensity score matching analysis (fondaparinux versus enoxaparin) showed that
      the incidence of DVT was lower (relative risk 0.70, 95% confidence interval (CI)
      0.58 to 0.85, P = 0.002 in TKA and relative risk 0.73, 95% CI 0.53 to 0.99, P =
      0.134 in THA) but that the incidence of major bleeding was higher in the
      fondaparinux than in the enoxaparin group (3.4% versus 0.5%, P = 0.062 in TKA and
      4.9% versus 0%, P = 0.022 in THA). CONCLUSIONS: These findings indicate that
      prophylaxis with fondaparinux, not enoxaparin, reduces the risk of DVT but
      increases bleeding tendency in patients undergoing TKA and THA. TRIAL
      REGISTRATION: University Hospital Medical Information Network Clinical Trials
      Registry: UMIN000001366. Registered 11 September 2008.

PMID- 25047863
TI  - Yeast synthetic biology for high-value metabolites.
AB  - Traditionally, high-value metabolites have been produced through direct
      extraction from natural biological sources which are inefficient, given the low
      abundance of these compounds. On the other hand, these high-value metabolites are
      usually difficult to be synthesized chemically, due to their complex structures.
      In the last few years, the discovery of genes involved in the synthetic pathways
      of these metabolites, combined with advances in synthetic biology tools, has
      allowed the construction of increasing numbers of yeast cell factories for
      production of these metabolites from renewable biomass. This review summarizes
      recent advances in synthetic biology in terms of the use of yeasts as microbial
      hosts for the identification of the pathways involved in the synthesis, as well
      as for the production of high-value metabolites.

PMID- 25047864
TI  - Definitions for the sonographic features of joints in healthy children.
AB  - OBJECTIVE: Musculoskeletal ultrasonography (US) has potential in the assessment
      of disease activity and structural damage in childhood arthritides. In order to
      assess pathology, the US characteristics of joints in healthy children need to be
      defined first. The aim of this study was to develop definitions for the various
      components of the normal pediatric joint. METHODS: The definitions were developed
      by an expert group and applicability was assessed on a collection of standardized
      scans of the knee and ankle joints by scoring the scans on a Likert scale. The
      definitions were then modified and applicability was reassessed before sending
      the definitions for approval to a larger panel of experts. A final scoring on
      stored images of all relevant joints at different ages followed. RESULTS: Five
      definitions were developed addressing the articular bone, cartilage, joint
      capsule, epiphyseal ossification center, and synovial membrane. In total, 224 US
      images of knees and ankles were acquired, of which 172 were selected for scoring.
      An agreement of >=80% was not met for any of the definitions, but after
      modifications, 81-97% agreement was reached. This version of the definitions was
      approved by 15 US experts. In the final validation exercise, all definitions
      reached an agreement of >=80% for the shoulder, elbow, wrist, metacarpophalangeal
      hip, knee, ankle and metatarsophalangeal joint. CONCLUSION: US definitions for
      the normal pediatric joint were successfully developed through a Delphi process
      and validated in a practical exercise. These results provide the basis to develop
      definitions for pathology and to support the standardized use of US in pediatric
      rheumatology.

PMID- 25047865
TI  - Susceptibility artefact correction using dynamic graph cuts: application to
      neurosurgery.
AB  - Echo Planar Imaging (EPI) is routinely used in diffusion and functional MR
      imaging due to its rapid acquisition time. However, the long readout period makes
      it prone to susceptibility artefacts which results in geometric and intensity
      distortions of the acquired image. The use of these distorted images for
      neuronavigation hampers the effectiveness of image-guided surgery systems as
      critical white matter tracts and functionally eloquent brain areas cannot be
      accurately localised. In this paper, we present a novel method for correction of
      distortions arising from susceptibility artefacts in EPI images. The proposed
      method combines fieldmap and image registration based correction techniques in a
      unified framework. A phase unwrapping algorithm is presented that can efficiently
      compute the B0 magnetic field inhomogeneity map as well as the uncertainty
      associated with the estimated solution through the use of dynamic graph cuts.
      This information is fed to a subsequent image registration step to further refine
      the results in areas with high uncertainty. This work has been integrated into
      the surgical workflow at the National Hospital for Neurology and Neurosurgery and
      its effectiveness in correcting for geometric distortions due to susceptibility
      artefacts is demonstrated on EPI images acquired with an interventional MRI
      scanner during neurosurgery. 

PMID- 25047866
TI  - Multi-shell diffusion signal recovery from sparse measurements.
AB  - For accurate estimation of the ensemble average diffusion propagator (EAP),
      traditional multi-shell diffusion imaging (MSDI) approaches require acquisition
      of diffusion signals for a range of b-values. However, this makes the acquisition
      time too long for several types of patients, making it difficult to use in a
      clinical setting. In this work, we propose a new method for the reconstruction of
      diffusion signals in the entire q-space from highly undersampled sets of MSDI
      data, thus reducing the scan time significantly. In particular, to sparsely
      represent the diffusion signal over multiple q-shells, we propose a novel
      extension to the framework of spherical ridgelets by accurately modeling the
      monotonically decreasing radial component of the diffusion signal. Further, we
      enforce the reconstructed signal to have smooth spatial regularity in the brain,
      by minimizing the total variation (TV) norm. We combine these requirements into a
      novel cost function and derive an optimal solution using the Alternating
      Directions Method of Multipliers (ADMM) algorithm. We use a physical phantom data
      set with known fiber crossing angle of 45 degrees  to determine the optimal
      number of measurements (gradient directions and b-values) needed for accurate
      signal recovery. We compare our technique with a state-of-the-art sparse
      reconstruction method (i.e., the SHORE method of Cheng et al. (2010)) in terms of
      angular error in estimating the crossing angle, incorrect number of peaks
      detected, normalized mean squared error in signal recovery as well as error in
      estimating the return-to-origin probability (RTOP). Finally, we also demonstrate
      the behavior of the proposed technique on human in vivo data sets. Based on these
      experiments, we conclude that using the proposed algorithm, at least 60
      measurements (spread over three b-value shells) are needed for proper recovery of
      MSDI data in the entire q-space. 

PMID- 25047867
TI  - Assessment of left ventricular mechanical dyssynchrony by phase analysis of gated
      SPECT myocardial perfusion imaging and tissue Doppler imaging: comparison between
      QGS and ECTb software packages.
AB  - BACKGROUND: Recently, the phase analysis of gated single-photon emission computed
      tomography (SPECT) myocardial perfusion imaging (MPI) has become feasible via
      several software packages for the evaluation of left ventricular mechanical
      dyssynchrony. We compared two quantitative software packages, quantitative gated
      SPECT (QGS) and Emory cardiac toolbox (ECTb), with tissue Doppler imaging (TDI)
      as the conventional method for the evaluation of left ventricular mechanical
      dyssynchrony. METHODS AND RESULTS: Thirty-one patients with severe heart failure
      (ejection fraction <=35%) and regular heart rhythm, who referred for gated-SPECT
      MPI, were enrolled. TDI was performed within 3 days after MPI. Dyssynchrony
      parameters derived from gated-SPECT MPI were analyzed by QGS and ECTb and were
      compared with the Yu index and septal-lateral wall delay measured by TDI. QGS and
      ECTb showed a good correlation for assessment of phase histogram bandwidth (PHB)
      and phase standard deviation (PSD) (r = 0.664 and r = 0.731, P < .001,
      respectively). However, the mean value of PHB and PSD by ECTb was significantly
      higher than that of QGS. No significant correlation was found between ECTb and
      QGS and the Yu index. Nevertheless, PHB, PSD, and entropy derived from QGS
      revealed a significant (r = 0.424, r = 0.478, r = 0.543, respectively; P < .02)
      correlation with septal-lateral wall delay. CONCLUSION: Despite a good
      correlation between QGS and ECTb software packages, different normal cut-off
      values of PSD and PHB should be defined for each software package. There was only
      a modest correlation between phase analysis of gated-SPECT MPI and TDI data,
      especially in the population of heart failure patients with both narrow and wide
      QRS complex.

PMID- 25047868
TI  - Computational and 13C investigations of the diazadienes and oxazadienes formed
      via the rearrangement of methylenecyclopropyl hydrazones and oximes.
AB  - Computational and further experimental investigations of the previously reported
      diazadienes, obtained via the rearrangement of methylenecyclopropyl hydrazone 1
      are reported. Calculations at the CCSD(T)/cc-pVTZ//B3LYP/6-31G(d) level of theory
      indicate that the initially reported product 3 would, if formed, undergo rapid
      electrocyclic ring opening and, hence, would be unstable under the reaction
      conditions. Based on this computational prediction, further analysis of the (13)C
      NMR spectrum, previously attributed to 3, led to the revision of structure 3 to
      that of its N-tosylaminopyrrole constitutional isomer 11. Similarly, structure 8,
      formed in the rearrangement of oxime 6, was revised to that of N-hydroxypyrrole
      12. 

PMID- 25047869
TI  - A school-based post-Katrina therapeutic intervention.
AB  - The current study presents the implementation of a set of school based
      interventions in a greater New Orleans school district one year following
      Hurricane Katrina. The interventions included adaptation and implementation of
      evidence based treatments in a crisis situation with at-risk youth which involved
      training and clinical challenges. 386 students found to have significant
      depressive and/or disruptive disorder symptoms received treatment from the School
      Therapeutic Enhancement Program (STEP). Further, a district-wide mental health
      needs assessment of middle and high school students (N = 11,861) screened for
      behavioral and emotional difficulties at the beginning and end of the school year
      provided a benchmark for community youth's emotional and behavioral distress.
      High-need intervention students demonstrated clinically significant lower levels
      of emotional and behavioral problems, depression and inattention in comparison to
      pre-treatment levels as indicated by multiple informants (i.e., self, parent,
      teacher). Self-reported distress levels were also lower than screening group
      students at post-test. These findings support the efficacy of a school-based
      intervention for youth struggling with the aftereffects of a highly disruptive
      natural disaster. Implications for utilizing a flexible adaptation of an evidence
      based training model involving coaching and consultation are discussed. 

PMID- 25047870
TI  - Integrating perovskite solar cells into a flexible fiber.
AB  - Perovskite solar cells have triggered a rapid development of new photovoltaic
      devices because of high energy conversion efficiencies and their all-solid-state
      structures. To this end, they are particularly useful for various wearable and
      portable electronic devices. Perovskite solar cells with a flexible fiber
      structure were now prepared for the first time by continuously winding an aligned
      multiwalled carbon nanotube sheet electrode onto a fiber electrode; photoactive
      perovskite materials were incorporated in between them through a solution
      process. The fiber-shaped perovskite solar cell exhibits an energy conversion
      efficiency of 3.3%, which remained stable on bending. The perovskite solar cell
      fibers may be woven into electronic textiles for large-scale application by well
      developed textile technologies.

PMID- 25047871
TI  - A novel method for the measurement of plasma metanephrines using online solid
      phase extraction-liquid chromatography tandem mass spectrometry.
AB  - BACKGROUND: Measurement of plasma metanephrine, normetanephrine and 3
      methoxytyramine is useful in the diagnosis of phaeochromocytomas, but many assays
      require a large volume of plasma due to poor assay sensitivity, and often require
      lengthy sample preparation. Our aim was to develop a method for measurement of
      plasma metanephrines using a small sample volume with minimal hands-on
      preparation. METHODS: Samples were deproteinised using 10 K spin filters prior to
      online solid phase extraction using a Waters Acquity UPLC Online SPE Manager
      (Waters, Manchester, UK) coupled to a Waters Xevo TQ-S mass spectrometer (Waters,
      Manchester, UK). The assay was validated and results compared to a previously
      published method. RESULTS: We achieved a limit of quantification of 37.5 pmol/L
      for metanephrine and 3-methoxytyramine and 75 pmol/L for normetanephrine using
      only 150 uL of sample. The assay was linear up to 30,000 pmol/L for all analytes
      and in a method comparison study results showed good agreement with a previously
      published LC-MS/MS assay. CONCLUSIONS: We have developed a simple method for
      measurement of plasma metanephrine, normetanephrine and 3-methoxytyramine using
      only 150 uL of sample. There is minimal hands-on sample preparation required and
      the assay is suitable for routine use in a clinical laboratory.

PMID- 25047872
TI  - Assessing essentiality of transketolase in Mycobacterium tuberculosis using an
      inducible protein degradation system.
AB  - Improved genetic tools are required to identify new drug targets in Mycobacterium
      tuberculosis. To this aim, genetic approaches, targeting either transcription
      and/or protein degradation, have been developed to appraise gene essentiality and
      to test the impact of gene silencing on bacterial survival. Here, we successfully
      combined the Tet-Pip OFF system, which downregulates transcription through the
      TetR and Pip repressors, with SspB-mediated protein degradation to study
      depletion of the transketolase encoded by the tkt (rv1449c) gene. We show that
      depletion of Tkt using the RNA silencing and protein degradation (RSPD) system
      arrested growth of M. tuberculosis in vitro faster than the Tet-Pip OFF system
      alone. In addition, we extended the new combined approach to an ex vivo model of
      M. tuberculosis infection in THP-1 cells. Tkt-depleted bacteria displayed reduced
      virulence as compared to wild type bacilli, thus confirming the essentiality of
      the enzyme for intracellular growth.

PMID- 25047873
TI  - Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in
      gene expression of growth factors in two developmental stages of the female rat.
AB  - Oxytocin production and secretion is important for early development of the
      brain. Long-term consequences of manipulation of oxytocin system might include
      changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins.
      The aim of the present study was (1) to determine whether neonatal oxytocin
      administration affects gene expression of nestin, microtubule-associated protein
      2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF)
      in the brain of two developmental stages of rat and (2) to evaluate whether
      neonatal oxytocin administration protects against lipopolysaccharide (LPS)
      induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight
      in the LPS treated animals. Oxytocin significantly increased gene expression of
      BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene
      expression of NGF and MAP-2 significantly increased in males treated with
      oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were
      reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the
      gene expression of only growth factors. In conclusion, neonatal manipulation of
      oxytocin has developmental and sex-dependent effect on markers of brain
      plasticity. These results also indicate, that oxytocin may be protective against
      inflammation particularly in females.

PMID- 25047874
TI  - Comparison of the efficacy of aflibercept, ranibizumab, and bevacizumab in an
      RPE/choroid organ culture.
AB  - PURPOSE: Anti-VEGF treatment is the therapy of choice in age-related macular
      degeneration and is also applied in diabetic macular edema or retinal vein
      occlusion. Recently, aflibercept has been approved for therapeutic use. In this
      study, we investigate the efficacy of aflibercept in comparison with the VEGF
      antagonists ranibizumab and bevacizumab in RPE/choroid organ cultures. METHODS:
      RPE/choroid organ cultures were prepared from freshly slaughtered pigs' eyes.
      Organ cultures were treated with 125 MUg/ml aflibercept, ranibizumab, or
      bevacizumab, and the VEGF content of the supernatant was evaluated over the
      course of 7 days. Additionally, the minimal concentration of VEGF inhibition was
      evaluated in organ cultures, measured after 6 h of application. RESULTS:
      Aflibercept was able to completely inhibit VEGF detection for 6 h at a minimal
      concentration of 0.031 MUg/ml, in contrast to bevacizumab (3.9 MUg/ml) and
      ranibizumab (0.244 MUg/ml). A statistically significant VEGF inhibition compared
      to control could be found for aflibercept and ranibizumab down to and including
      0.031 MUg/ml, while bevacizumab was significantly reduced compared to control
      down to a concentration of 0.244 MUg/ml and again at 0.061 MUg/ml. Inhibition of
      VEGF after a single aflibercept application of 125 MUg/ml could be found over the
      course of 7 days, with some VEGF detectable at the 7th day. In contrast, VEGF was
      detectable after 72 h of ranibizumab treatment and some VEGF could already be
      found 12 h after bevacizumab treatment. CONCLUSIONS: In conclusion, aflibercept
      displays a prolonged VEGF inhibition, confirming its effectiveness but also
      raising concerns about possible side effects of long-term usage.

PMID- 25047876
TI  - Surface binding of polypyrrole on porous silicon hollow nanospheres for Li-ion
      battery anodes with high structure stability.
AB  - Uniform porous silicon hollow nano-spheres are prepared without any sacrificial
      templates through a magnesio-thermic reduction of mesoporous silica hollow
      nanospheres and surface modified by the following in situ chemical polymerization
      of polypyrrole. The porous hollow structure and polypyrrole coating contribute
      significantly to the excellent structure stability and high electrochemical
      performance of the nanocomposite. 

PMID- 25047875
TI  - Hyperthermia-induced upregulation of vascular endothelial growth factor in
      retinal pigment epithelial cells is regulated by mitogen-activated protein
      kinases.
AB  - PURPOSE: Localized application of hyperthermia is a potential treatment for
      retinal diseases. Vascular endothelial growth factor (VEGF) derived from the
      retinal pigment epithelium (RPE) is implicated in a variety of retinal
      pathologies. As it has been recently shown that hyperthermia may induce VEGF in
      the RPE, the aim of this study was to investigate hyperthermia-induced VEGF
      secretion and the pathways of hyperthermal VEGF upregulation in the RPE. MATERIAL
      AND METHODS: The human RPE cell line (Arpe-19) was exposed to 40 degrees , 42
      degrees , 45 degrees  and 50  degrees C for one, five and 15 min. Cell viability
      was evaluated using a trypan blue exclusion assay, VEGF secretion was evaluated
      by an enzyme-linked immunosorbent assay ELISA) and VEGF expression was
      investigated using a Western blot. Involvement of mitogen-activated protein
      kinase (MAPK) pathways (ERK1/2, JNK, p38) and transient receptor potential
      vanilloid (TRPV) channels on VEGF induction was investigated using commercially
      available inhibitors (U0126, SB203580, SP600125, ruthenium red). Expression and
      phosphorylation of MAPKs was investigated using a Western blot. RESULTS:
      Hyperthermia induces time- and temperature-dependent cell death in human RPE
      cells. VEGF expression and secretion is induced by hyperthermia in a time- and
      temperature-dependent manner mediated by p38 and to a lesser degree by JNK. TRPV
      channels seem to play a minor role in regulation of hyperthermia-induced VEGF
      secretion. CONCLUSIONS: Hyperthermia induces temperature-dependent secretion of
      VEGF in the RPE, which is mediated by p38 and, to a lesser extent, JNK. This may
      lead to undesired effects from hyperthermal treatment of retinal diseases.

PMID- 25047877
TI  - Type 2 diabetes continuing medical education for general practitioners: what
      works? A systematic review.
AB  - AIMS: To perform a systematic review of studies that have assessed the
      effectiveness of interventions designed to improve healthcare professionals' care
      of patients with diabetes and to assess the effects of educational interventions
      targeted at general practitioners' diabetes management. METHODS: A computer
      search was conducted using the Cochrane Library, PubMed, Ovid MEDLINE, Scopus,
      EMBASE, Informit, Google scholar and ERIC from the earliest date of each database
      up until 2013. A supplementary review of reference lists from each article
      obtained was also carried out. Measured changes in general practitioners'
      satisfaction, knowledge, practice behaviours and patient outcomes were recorded.
      RESULTS: Thirteen out of 1255 studies met the eligibility criteria, but none was
      specifically conducted in rural or remote areas. Ten studies were randomized
      trials. Fewer than half of the studies (5/13, 38.5%) reported a significant
      improvement in at least one of the following outcome categories: satisfaction
      with the programme, knowledge and practice behaviour. There was little evidence
      of the impact of general practitioner educational interventions on patient
      outcomes. Of the five studies that examined patient outcomes, only one reported a
      positive impact: a reduction in patient HbA1c levels. CONCLUSIONS: Few studies
      examined the effectiveness of general practitioner Type 2 diabetes education in
      improving general practitioner satisfaction, knowledge, practices and/or patient
      outcomes. Evidence to support the effectiveness of education is partial and weak.
      To determine effective strategies for general practitioner education related to
      Type 2 diabetes, further well designed studies, accompanied by valid and reliable
      evaluation methods, are needed.

PMID- 25047878
TI  - A rare case series of concomitant inflammatory bowel disease, sporadic adenomas,
      and serrated polyposis syndrome.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) involving the colon is
      associated with an increased risk of colon cancer. Patients may develop sporadic
      adenomas further increasing their risk of colorectal cancer. Current knowledge of
      IBD with concomitant serrated polyposis syndrome (SPS) is limited. We describe
      four patients with both IBD and SPS. METHODS: Four patients with inflammatory
      bowel disease and hyperplastic polyps referred to Beth Israel Deaconess Medical
      Center meeting the World Health Organization (WHO) criteria for SPS were
      identified. RESULTS: Four patients with long standing IBD involving the colon
      were identified. All of these patients' IBD were in clinical remission.
      Additionally, 2 of the 4 patients were also noted to have sporadic adenomas. Each
      patient was also found to have multiple sessile serrated adenomas and
      hyperplastic polyps meeting the WHO criteria for SPS. Two of the patients had
      colonoscopy with chromoendoscopy which improved polyp detection. Discussions were
      held with each patient regarding the potentially increased risk of colorectal
      cancer with the combination of IBD and SPS. Patients were advised that colectomy
      would be the safest method to reduce the risk of cancer. None of the patients
      opted for colectomy and instead planned on a repeat colonoscopy with
      chromoendoscopy at 3-12 month intervals. CONCLUSION: Serrated polyposis syndrome
      develops in patients with IBD. It is unclear how high the risk of colon cancer is
      in patients who have both IBD and SPS and what the recommendations should be
      regarding the frequency of surveillance or surgery. Further studies are necessary
      to identify the optimal management of these patients.

PMID- 25047879
TI  - Implementation research - its importance and application in primary care.

PMID- 25047880
TI  - Co-creating value in research: stakeholders' perspectives.

PMID- 25047881
TI  - Key elements of high-quality practice organisation in primary health care: a
      systematic review.
AB  - OBJECTIVES: To identify elements that are integral to high-quality practice and
      determine considerations relating to high-quality practice organisation in
      primary care. STUDY DESIGN: A narrative systematic review of published and grey
      literature. DATA SOURCES: Electronic databases (PubMed, CINAHL, the Cochrane
      Library, Embase, Emerald Insight, PsycInfo, the Primary Health Care Research and
      Information Service website, Google Scholar) were searched in November 2013 and
      used to identify articles published in English from 2002 to 2013. Reference lists
      of included articles were searched for relevant unpublished articles and reports.
      DATA SYNTHESIS: Data were configured at the study level to allow for the
      inclusion of findings from a broad range of study types. Ten elements were most
      often included in the existing organisational assessment tools. A further three
      elements were identified from an inductive thematic analysis of descriptive
      articles, and were noted as important considerations in effective quality
      improvement in primary care settings. CONCLUSION: Although there are some
      validated tools available to primary care that identify and build quality, most
      are single-strategy approaches developed outside health care settings. There are
      currently no validated organisational improvement tools, designed specifically
      for primary health care, which combine all elements of practice improvement and
      whose use does not require extensive external facilitation.

PMID- 25047882
TI  - Development and pilot study of the Primary Care Practice Improvement Tool (PC
      PIT): an innovative approach.
AB  - OBJECTIVE: To assess the usability and validity of the Primary Care Practice
      Improvement Tool (PC-PIT), a practice performance improvement tool based on 13
      key elements identified by a systematic review. It was co-created with a range of
      partners and designed specifically for primary health care. DESIGN: This pilot
      study examined the PC-PIT using a formative assessment framework and mixed
      methods research design. SETTING AND PARTICIPANTS: Six high-functioning general
      practices in Queensland, Australia, between February and July 2013. A total of 28
      staff participated - 10 general practitioners, six practice or community nurses,
      12 administrators (four practice managers; one business manager and eight
      reception or general administrative staff). MAIN OUTCOME MEASURES: Readability,
      content validity and staff perceptions of the PC-PIT. RESULTS: The PC-PIT offers
      an appropriate and acceptable approach to internal quality improvement in general
      practice. Quantitative assessment scores and qualitative data from all staff
      identified two areas in which the PC-PIT required modification: a reduction in
      the indicative reading age, and simplification of governance-related terms and
      concepts. CONCLUSION: The PC-PIT provides an innovative approach to address the
      complexity of organisational improvement in general practice and primary health
      care. This initial validation will be used to develop a suite of supporting, high
      quality and free-to-access resources to enhance the use of the PC-PIT in general
      practice. Based on these findings, a national trial is now underway.

PMID- 25047883
TI  - Surveyors' perceptions of the impact of accreditation on patient safety in
      general practice.
AB  - OBJECTIVES: To explore Australian General Practice Accreditation Limited (AGPAL)
      surveyors' perceptions of the impact of accreditation on patient safety and to
      elicit suggestions for improving patient safety in Australian general practices.
      DESIGN, SETTING AND PARTICIPANTS: We conducted semi-structured telephone
      interviews with a purposive national sample of 10 AGPAL surveyors from 2 July to
      14 December 2012. All interviews were audio recorded, transcribed and summarised.
      RESULTS: All participants agreed that accreditation has improved general
      practices' performance in quality and safety. Participants noted specific areas
      that need further attention, including sufficient evidence for clinical risk
      management, which half the participants estimated occurs in about 5%-10% of
      Australian general practices. Tangible evidence of patient safety activities
      included having a significant incidents register, providing documentation of near
      misses, slips, lapses or mistakes, and engaging in regular clinical meetings to
      discuss incidents and how to avoid them in the future. Participants agreed that
      the accreditation process could be improved through the inclusion of tighter
      clinical safety indicators and the requirement of verifiable evidence of a
      working clinical risk management system. CONCLUSIONS: Accreditation has had a
      positive role in improving quality and safety in general practice. The inclusion
      of tighter indicators that require verifiable evidence will be a step forward.
      The Australian Primary Care Collaboratives (APCC) Program has an opportunity to
      build on its previous success in general practice quality improvement to further
      enhance patient safety in general practice.

PMID- 25047884
TI  - Patients' and carers' perceptions of safety in rural general practice.
AB  - OBJECTIVES: To explore patients' and carers' experiences of rural general
      practice to identify their perceptions of safety of care. DESIGN, PARTICIPANTS
      AND SETTING: Four focus group interviews were conducted with 26 rural patients
      and carers in south-west Victoria between September and December 2012. Frequent
      users of general practice were recruited from local allied health self-management
      programs and a mothers' group. Focus groups were audio recorded, transcripts were
      independently analysed and interpreted using narrative methodologies. RESULTS:
      Participants who had experienced some level of harm were able to comment more
      extensively on safety aspects of care. Several key themes related to safety were
      identified from the analysis of all participant narratives. An assumed sense of
      safety in general practice was predominant, and was influenced by participants'
      level of risk awareness and trust in their general practitioner. Additional
      unique themes included feelings of vulnerability, desire for an explanation and
      apology, a forgiving view of mistakes, and preference for GP interpersonal skills
      over competence. CONCLUSIONS: This study revealed new insights into the factors
      that influence patients' and carers' perspectives of safety, and demonstrated the
      value of incorporating the patient voice into safety research. An assumed sense
      of safety due to a default position of trust, coupled with limited risk
      perception, directly contests the current literature on patient involvement in
      safety. Further exploration is required to determine how patients and carers can
      effectively engage in and assist with improving safety in general practice.

PMID- 25047885
TI  - Best-practice integrated health care governance - applying evidence to
      Australia's health reform agenda.

PMID- 25047886
TI  - What should governance for integrated care look like? New Zealand's alliances
      provide some pointers.

PMID- 25047887
TI  - A systematic review of the challenges to implementation of the patient-centred
      medical home: lessons for Australia.
AB  - OBJECTIVE: To review the available literature to identify the major challenges
      and barriers to implementation and adoption of the patient-centred medical home
      (PCMH) model, topical in current Australian primary care reforms. STUDY DESIGN:
      Systematic review of peer-reviewed literature. DATA SOURCES: PubMed and Embase
      databases were searched in December 2012 for studies published in English between
      January 2007 and December 2012. STUDY SELECTION: Studies of any type were
      included if they defined PCMH using the Patient-Centered Primary Care
      Collaborative Joint Principles, and reported data on challenges and barriers to
      implementation and adoption of the PCMH model. DATA EXTRACTION: One researcher
      with content knowledge in the area abstracted data relating to the review
      objective and study design from eligible articles. A second researcher reviewed
      the abstracted data alongside the original article to check for accuracy and
      completeness. DATA SYNTHESIS: Thematic synthesis was used to in three stages:
      free line-by-line coding of data; organisation of "free codes" into related areas
      to construct "descriptive" themes and develop "analytical" themes. The main
      barriers identified related to: challenges with the transformation process;
      difficulties associated with change management; challenges in implementing and
      using an electronic health record that administers principles of PCMH; challenges
      with funding and appropriate payment models; insufficient resources and
      infrastructure within practices; and inadequate measures of performance.
      CONCLUSION: This systematic review documents the key challenges and barriers to
      implementing the PCMH model in United States family practice. It provides
      valuable evidence for Australian clinicians, policymakers, and organisations
      approaching adoption of PCMH elements within reform initiatives in this country.

PMID- 25047888
TI  - Primary care of women after gestational diabetes mellitus: mapping the evidence
      practice gap.
AB  - OBJECTIVE: To determine the extent to which preventive activities, including the
      ordering of an oral glucose tolerance test (OGTT) between 6 and 12 weeks of
      birth, are integrated into women's primary care postpartum visits after a
      gestational diabetes mellitus (GDM)-affected pregnancy. DESIGN AND SETTING:
      Prospective survey and retrospective chart audit of general practices that
      provide maternity shared care in south-east Queensland, July 2011 to June 2012.
      PARTICIPANTS: General practitioners (n = 38) and medical records of women to whom
      they provided care (n = 43 women). MAIN OUTCOME MEASURES: GPs' awareness and
      knowledge of GDM guidelines and delivery of postpartum preventive care. RESULTS:
      The response rate for the survey/chart audit was 47%. All respondents recommended
      an OGTT between 6 and 12 weeks; a variety of guidelines informed practice; and
      weight, blood pressure and infant feeding practices were regularly checked.
      Mental health status and diet and exercise were discussed less consistently.
      CONCLUSIONS: GPs surveyed knew guidelines around the timing and type of test for
      women who have experienced GDM, and the audit demonstrated that this knowledge is
      translated into practice. Adherence to preventive screening and advice was less
      consistent. This problem may exist due to the absence of a systems approach to
      care, resulting in a lost opportunity to systematically reduce the incidence of
      type 2 diabetes and promote the wellbeing of women and their infants.

PMID- 25047889
TI  - Who's responsible for the care of women during and after a pregnancy affected by
      gestational diabetes?
AB  - Despite its increasing incidence and high conferred risk to women and their
      children, gestational diabetes mellitus (GDM) is managed inconsistently during
      and after pregnancy due to an absence of a systemic approach to managing these
      women. New guidelines for GDM testing and diagnosis are based on stronger
      evidence, but raise concerns about increased workloads and confusion in a
      landscape of multiple, conflicting guidelines. Postnatal care and long-term
      preventive measures are particularly fragmented, with no professional group
      taking responsibility for this crucial role. Clearer guidelines and assistance
      from existing frameworks, such as the National Gestational Diabetes Register,
      could enable general practitioners to take ownership of the management of women
      at risk of type 2 diabetes following GDM, applying the principles of chronic
      disease management long term. 

PMID- 25047890
TI  - Monetary delay discounting in gambling and cocaine dependence with personality
      comorbidities.
AB  - BACKGROUND: Cocaine addiction and pathological gambling are commonly associated
      with steeper (impulsive) discounting of delayed rewards, which promotes ongoing
      drug and gambling behaviors. However, it is yet unclear whether impulsive delay
      discounting is a stable trait in cocaine and gambling disorders during
      abstinence, and whether it is significantly impacted by dysfunctional personality
      beliefs. METHODS: The aim of this study was to compare the delay discounting
      rates of four groups: 47 cocaine users with comorbid personality disorders, 41
      cocaine users without psychiatric comorbidities, 28 pathological gamblers without
      psychiatric comorbidities, and 36 healthy comparison individuals. We also
      examined the association between dysfunctional personality beliefs and delay
      discounting rates. Participants completed the Kirby Delay Discounting
      Questionnaire and the Beck Personality Belief Questionnaire as part of a larger
      battery. RESULTS: We used non-parametric tests to compare discounting rates
      between the groups, and bivariate correlation analyses to examine the association
      between beliefs and discounting rates within each of the groups. We found that
      discounting rates were significantly higher in individuals with disordered
      gambling compared to controls. Specifically in cocaine users with Cluster B
      personality disorders, higher discounting rates were associated with the
      intensity of "dependent" dysfunctional beliefs (e.g., "I am needy and weak").
      Conclusion:We conclude that impulsive delay discounting is increased in gambling
      relative to controls and linked to personality beliefs in cocaine users with
      Cluster B personality disorders.

PMID- 25047891
TI  - Electrostatic free energies in translational GTPases: Classic allostery and the
      rest.
AB  - GTPases typically switch between an inactive, OFF conformation and an active, ON
      conformation when a GDP ligand is replaced by GTP. Their ON/OFF populations and
      activity thus depend on the stabilities of four protein complexes, two apo
      protein forms, and GTP/GDP in solution. A complete characterization is usually
      not possible experimentally and poses major challenges for simulations. We review
      the most important methodological challenges and we review thermodynamic data for
      two GTPases involved in translation of the genetic code: archaeal Initiation
      Factors 2 and 5B (aIF2, aIF5B). One main challenge is the multiplicity of states
      and conformations, including those of GTP/GDP in solution. Another is force field
      accuracy, especially for interactions of GTP/GDP with co-bound divalent Mg(2+)
      ions. The calculation of electrostatic free energies also poses specific
      challenges, and requires careful protocols. For aIF2, experiments and earlier
      simulations showed that it is a "classic" GTPase, with distinct ON/OFF
      conformations that prefer to bind GTP and GDP, respectively. For aIF5B, we
      recently proposed a non-classic mechanism, where the ON/OFF states differ only in
      the protonation state of Glu81 in the nucleotide binding pocket. This model is
      characterized here using free energy simulations. The methodological analysis
      should help future studies, while the aIF2, aIF5B examples illustrate the
      diversity of ATPase/GTPase mechanisms. This article is part of a Special Issue
      entitled Recent developments of molecular dynamics. 

PMID- 25047892
TI  - Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway:
      involvement of MMP-2.
AB  - In this study, the role of epidermal growth factor receptor (EGFR), extracellular
      signal-regulated kinase (ERK1/2), heparin-binding EGF-like growth factor (HB
      EGF), general metalloproteinases, matrix metalloproteinases-2 (MMP-2) in
      mediating the mitogenic action of thrombin in rat vascular smooth muscle cells
      (VSMC) was investigated. The incubation of rat VSMC with thrombin (1 U/ml) for 5
      min resulted in significant (p < 0.001) increase of ERK1/2 phosphorylation by 8.7
      +/- 0.9-fold, EGFR phosphorylation by 8.5 +/- 1.3-fold (p < 0.001) and DNA
      synthesis by 3.6 +/- 0.4-fold (p < 0.001). Separate 30-min pretreatments with
      EGFR tyrosine kinase irreversible inhibitor, 10 uM PD169540 (PD), and 20 uM anti
      HB-EGF antibody significantly reduced thrombin-stimulated EGFR and ERK1/2
      phosphorylation by 81, 72 % and by 48 and 61 %, respectively. Furthermore, the
      same pretreatments with PD or anti-HB-EGF antibody reduced thrombin-induced VSMC
      proliferation by 44 and 45 %, respectively. In addition, 30-min pretreatments
      with 10 uM specific MMP-2 inhibitor significantly reduced thrombin-stimulated
      phosphorylation of both EGFR and ERK1/2 by 25 %. Moreover, the same pretreatment
      with MMP-2 inhibitor reduced thrombin-induced VSMC proliferation by 45 %. These
      results show that the thrombin-induced DNA synthesis correlates with the level of
      ERK1/2 activation rather than EGFR activation. These results further suggest that
      thrombin acts through EGFR and ERK 1/2 signaling pathways involving MMP-2 to
      upregulate proliferation of VSMC.

PMID- 25047893
TI  - Congenital lipodystrophies and dyslipidemias.
AB  - Lipodystrophies are rare acquired and genetic disorders characterized by the
      selective loss of adipose tissue. One key metabolic feature of patients with
      congenital inherited lipodystrophy is hypertriglyceridemia. The precise
      mechanisms by which the lack of adipose tissue causes dyslipidemia remain largely
      unknown. In recent years, new insights have arisen from data obtained in vitro in
      adipocytes, yeast, drosophila, and very recently in several genetically modified
      mouse models of generalized lipodystrophy. A common metabolic pathway involving
      accelerated lipolysis and defective energy storage seems to contribute to the
      dyslipidemia associated with congenital generalized lipodystrophy syndromes,
      although the pathophysiological changes may vary with the nature of the mutation
      involved. Therapeutic management of dyslipidemia in patients with lipodystrophy
      is primarily based on specific approaches using recombinant leptin therapy.
      Preclinical studies suggest a potential efficacy of thiazolidinediones that
      remains to be assessed in dedicated clinical trials. 

PMID- 25047894
TI  - Relationship between calcified carotid atheromas in digital panoramic radiographs
      and underlying systemic diseases in implant patients.
AB  - AIM: The aim of the present study was to evaluate the correlation between
      calcified carotid atheromas (CCA) detected on digital panoramic radiographs and
      underlying systemic diseases. METHODS: Panoramic radiographs and underlying
      systemic diseases of retained mandibular denture implants in 265 patients (56
      males, 209 females) aged over 50 years were retrospectively evaluated at the
      Dental Unit of Prasat Neurological Institute, Bangkok, Thailand. RESULTS: The
      mean age of the patients was 71 +/- 7.1 years. The prevalence of CCA was 38.49%.
      The major underlying systemic diseases were hypertension, hyperlipidemia,
      diabetes mellitus, and cardiovascular diseases (CVD), respectively. No
      relationship was found among these four systemic diseases in detecting CCA on
      panoramic radiographs. Similar findings were also observed in patients with only
      one systemic disease versus in combination with other diseases. CONCLUSIONS: The
      presence of CCA on dental panoramic radiographs was not found to be related to
      the presence of underlying systemic diseases, including hypertension,
      hyperlipidemia, diabetes mellitus, and CVD.

PMID- 25047895
TI  - Single-nucleotide polymorphism data support the general unrelatedness of the
      males in the agricultural health study.
AB  - BACKGROUND: Farming is often a family and multigenerational business. Relatedness
      among farmers could bias gene-environment interaction analysis. To evaluate the
      potential relatedness of farmers, we used data from a nested case-control study
      of prostate cancer conducted in the Agricultural Health Study (AHS), a
      prospective study of farmers in Iowa and North Carolina. METHODS: We analyzed the
      genetic data for 25,009 SNPs (single-nucleotide polymorphisms) from 2,220 White
      participants to test for cryptic relatedness among these farmers. We used two
      software packages: (i) PLINK, to calculate inbreeding coefficients and identity
      by-descent (IBD) statistics and (ii) EIGENSOFT, to perform a principal component
      analysis on the genetic data. RESULTS: Inbreeding coefficients estimates and IBD
      statistics show that the subjects are overwhelmingly unrelated, with little
      potential for cryptic relatedness in these data. CONCLUSIONS: Our analysis
      rejects the hypothesis that individuals in the case-control study exhibit cryptic
      relatedness. IMPACT: These findings are important for all subsequent analyses of
      gene-environment interactions in the AHS.

PMID- 25047896
TI  - Dietary one-carbon nutrient intake and risk of lymphoid and myeloid neoplasms:
      results of the Netherlands cohort study.
AB  - BACKGROUND: Previous epidemiologic research suggests a protective role of one
      carbon nutrients in carcinogenesis. Folate, however, may play a dual role in
      neoplasms development: protect early in carcinogenesis and promote carcinogenesis
      at a later stage. We prospectively examined associations between intake of total
      folate, methionine, riboflavin, vitamin B6, and risk of lymphoid and myeloid
      neoplasms (including subtypes) and investigated whether alcohol modified the
      effects of folate. METHODS: The Netherlands Cohort Study consists of 120,852
      individuals who completed a baseline questionnaire in 1986, including a 150-item
      food-frequency questionnaire. After 17.3 years of follow-up, 1,280 cases of
      lymphoid and 222 cases of myeloid neoplasms were available for analysis. RESULTS:
      Intakes of folate, methionine, and riboflavin were not associated with lymphoid
      or myeloid neoplasms. For vitamin B6, a statistically significantly increased
      myeloid neoplasms risk was observed (highest vs. lowest quintile: HR = 1.87; 95%
      confidence intervals, 1.08-3.25). When analyzing by lymphoid and myeloid
      neoplasms subtypes, no clear associations were observed for most subtypes, with
      just a few increased risks for some subtypes and nutrients. Some risks became
      nonsignificant after excluding early cases. No interaction between alcohol and
      folate was observed. CONCLUSIONS: We observed a few significant positive
      associations; however, some of these would be expected to arise due to chance
      alone. Furthermore, some risks became nonsignificant after excluding early cases.
      Therefore, we conclude that there is no association between one-carbon nutrient
      intake and risk of lymphoid and myeloid neoplasms. IMPACT: This study contributes
      substantially to the limited and inconclusive evidence on the association with
      one-carbon nutrients.

PMID- 25047897
TI  - Assessment of vaginal atrophy: a review.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study is to provide an evidence
      based definition of vaginal atrophy (VA) and present an overview of subjective
      and objective measurements of VA applicable in clinical practice and research.
      METHODS: A systematic literature search was performed in MEDLINE and EMBASE to
      identify studies reporting on measurement properties of diagnostic instruments
      for VA. Additional searches in MEDLINE aimed to document the definitions,
      diagnostic criteria, and outcome measures of VA. Studies reporting on
      definitions, diagnosis, outcome measurements, and measurement properties of
      diagnostic instruments of VA were selected. RESULTS: Specific symptoms for VA
      that were consistently described could be identified to suggest an evidence-based
      definition of VA. As subjective outcome measurements, seven scoring systems to
      assess the signs of VA during physical examination were identified. The most
      bothersome symptom (MBS) approach is most useful in clinical practice and
      research as it focuses on the most common symptoms of VA. As objective outcome
      measurements, numerous ways to assess vaginal cytology and vaginal pH were
      identified. CONCLUSIONS: At the moment, there is no consensus on the definition
      and assessment of VA. We propose to define VA as a common manifestation of
      estrogen decline associated with specific symptoms of which the most common are:
      vaginal dryness, itching or irritation, and dyspareunia. In both clinical and
      research settings, subjective assessment (the MBS approach) and objective
      assessments of VA (measurement of vaginal maturation index and vaginal pH) should
      be combined.

PMID- 25047899
TI  - Comments on Badejoko et al.: Overflow urinary incontinence due to bladder stones.

PMID- 25047898
TI  - Association between metabolic syndrome and pelvic organ prolapse severity.
AB  - INTRODUCTION AND HYPOTHESIS: As in the case of cardiovascular and metabolic
      diseases, the prevalence of pelvic organ prolapse (POP) has been rising with the
      increasing proportion of elderly women in the population. The purpose of the
      present cross-sectional study was to evaluate the components of metabolic
      syndrome (MS) in urogynecological patients with a variable POP severity. METHODS:
      The MS risk factors (elevated waist circumference, elevated triglycerides,
      decreased high-density lipoprotein cholesterol, elevated blood pressure,
      hyperglycemia) were assessed in 100 women who were referred to our
      urogynecological center with pelvic floor disorders (PFD). POP was evaluated with
      the Pelvic Organ Prolapse Quantification system (POP-Q). RESULTS: The chi (2)
      test revealed that the diagnosis of MS and the presence of elevated triglycerides
      increased with the overall POP-Q stage. The other MS risk factors were not
      significantly associated with the overall POP-Q stage. MS and elevated
      triglycerides were predictors of the POP-Q stage >=III [odds ratio (OR) 3.5, 95 %
      confidence interval (CI) 1.5-8.2 for MS and OR 3.4, 95 % CI 1.4-8.2 for elevated
      triglycerides, p < 0.01]. CONCLUSIONS: The diagnosis of MS and the presence of
      elevated triglycerides may be associated with the severity of POP in
      urogynecological patients. Longitudinal studies are required to assess whether
      the MS risk factors might predict the progression of POP and whether elimination
      of the risk factors might improve the prognosis in POP patients.

PMID- 25047900
TI  - My Activity Coach - using video-coaching to assist a web-based computer-tailored
      physical activity intervention: a randomised controlled trial protocol.
AB  - BACKGROUND: There is a need for effective population-based physical activity
      interventions. The internet provides a good platform to deliver physical activity
      interventions and reach large numbers of people at low cost. Personalised advice
      in web-based physical activity interventions has shown to improve engagement and
      behavioural outcomes, though it is unclear if the effectiveness of such
      interventions may further be improved when providing brief video-based coaching
      sessions with participants. The purpose of this study is to determine the
      effectiveness, in terms of engagement, retention, satisfaction and physical
      activity changes, of a web-based and computer-tailored physical activity
      intervention with and without the addition of a brief video-based coaching
      session in comparison to a control group. METHODS/DESIGN: Participants will be
      randomly assigned to one of three groups (tailoring + online video-coaching,
      tailoring-only and wait-list control). The tailoring + video-coaching
      participants will receive a computer-tailored web-based physical activity
      intervention ('My Activity Coach') with brief coaching sessions with a physical
      activity expert over an online video calling program (e.g. Skype). The tailoring
      only participants will receive the intervention but not the counselling sessions.
      The primary time point's for outcome assessment will be immediately post
      intervention (week 9). The secondary time points will be at 6 and 12 months post
      baseline. The primary outcome, physical activity change, will be assessed via the
      Active Australia Questionnaire (AAQ). Secondary outcome measures include
      correlates of physical activity (mediators and moderators), quality of life
      (measured via the SF-12v2), participant satisfaction, engagement (using web-site
      user statistics) and study retention. DISCUSSION: Study findings will inform
      researchers and practitioners about the feasibility and effectiveness of brief
      online video-coaching sessions in combination with computer-tailored physical
      activity advice. This may increase intervention effectiveness at an acceptable
      cost and will inform the development of future web-based physical activity
      interventions. TRIAL REGISTRATION: ACTRN12614000339651Date: 31/03/2014.

PMID- 25047901
TI  - When it hurts (and helps) to try: the role of effort in language learning.
AB  - Compared to children, adults are bad at learning language. This is
      counterintuitive; adults outperform children on most measures of cognition,
      especially those that involve effort (which continue to mature into early
      adulthood). The present study asks whether these mature effortful abilities
      interfere with language learning in adults and further, whether interference
      occurs equally for aspects of language that adults are good (word-segmentation)
      versus bad (grammar) at learning. Learners were exposed to an artificial language
      comprised of statistically defined words that belong to phonologically defined
      categories (grammar). Exposure occurred under passive or effortful conditions.
      Passive learners were told to listen while effortful learners were instructed to
      try to 1) learn the words, 2) learn the categories, or 3) learn the category
      order. Effortful learners showed an advantage for learning words while passive
      learners showed an advantage for learning the categories. Effort can therefore
      hurt the learning of categories. 

PMID- 25047902
TI  - Revealing carbon nanodots as coreactants of the anodic electrochemiluminescence
      of Ru(bpy)32+.
AB  - Recently, research on carbon nanodots (C-dots), a new type of luminescent
      nanoparticles with superior optical properties, biocompatibility, and low cost,
      has been focused on exploring novel properties and structure-related mechanisms
      to extend their scope. Herein, electrochemiluminescence, a surface-sensitive
      tool, is used to probe the unrevealed property of carbon nanodots which is
      characterized by surface oxygen-containing groups. Together with
      chemiluminescence, carbon nanodots as the coreactants for the anodic
      electrochemiluminescence of Ru(bpy)3(2+) are demonstrated for the first time.
      During the anodic scan, the benzylic alcohol units on the C-dots surface are
      oxidized "homogeneously" by electrogenerated-Ru(bpy)3(3+) to form reductive
      radical intermediate, which further reduce Ru(bpy)3(3+) into Ru(bpy)3(2+)* that
      produces a strong ECL emission. This work has provided an insight into the ECL
      mechanism of the C-dots-involved system, which will be beneficial for in-depth
      understanding of some peculiar phenomena of C-dots, such as photocatalytic
      activity and redox properties. Moreover, because of the features of C-dots, the
      ECL system of Ru(bpy)3(2+)/C-dots is more promising in the bioanalysis. 

PMID- 25047903
TI  - Demonstration of a common indole-based aromatic core in natural and synthetic
      eumelanins by solid-state NMR.
AB  - Despite the essential functions of melanin pigments in diverse organisms and
      their roles in inspiring designed nanomaterials for electron transport and drug
      delivery, the structural frameworks of the natural materials and their biomimetic
      analogs remain poorly understood. To overcome the investigative challenges posed
      by these insoluble heterogeneous pigments, we have used l-tyrosine or dopamine
      enriched with stable (13)C and (15)N isotopes to label eumelanins metabolically
      in cell-free and Cryptococcus neoformans cell systems and to define their
      molecular structures and supramolecular architectures. Using high-field two
      dimensional solid-state nuclear magnetic resonance (NMR), our study directly
      evaluates the assumption of structural commonality between synthetic melanin
      models and the corresponding natural pigments, demonstrating a common indole
      based aromatic core in the products from contrasting synthetic protocols for the
      first time. 

PMID- 25047904
TI  - Cytotoxic and apoptotic activities of the plancitoxin I from the venom of crown
      of-thorns starfish (Acanthaster planci) on A375.S2 cells.
AB  - This study reports on a cytotoxic toxin derived from the venom of the crown-of
      thorns starfish Acanthaster planci (CAV). The protein toxin was isolated through
      both ion-exchange and gel-filtration chromatography, and characterized by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrum
      analyzes. The CAV was identified as plancitoxin I protein. The mechanistic role
      of the CAV toxin was explored in human malignant melanoma A375.S2 cell death. The
      results indicated that after incubation with CAV toxin, cells significantly
      decreased in A375.S2 cell viability and increased in the lactate dehydrogenase
      (LDH) level in a dose-dependent manner. The assays indicated that CAV toxin
      promoted reactive oxygen species (ROS) production, induced nitric oxide (NO)
      formation, lost mitochondrial membrane potential (DeltaPsim) and induced inter
      nucleosomal DNA fragmentation in A375.S2 cells. The molecular cytotoxicity of the
      CAV toxin was tested through evaluation of the apoptosis/necrosis ratio by double
      staining with annexin V-FITC and a propidium iodide (PI) assay. The results
      suggested that CAV toxin induced a cytotoxic effect in A375.S2 cells via the
      apoptotic procedure, and may be associated with the regulation of the p38
      pathways.

PMID- 25047905
TI  - Application of a SYBR(r)Green one step real-time RT-PCR assay to detect type 1
      porcine reproductive and respiratory syndrome virus.
AB  - The emergence in Japan of field isolates of type 1 porcine reproductive and
      respiratory syndrome virus (PRRSV) suggests problems with control. We therefore
      developed a one-step real-time reverse transcription polymerase chain reaction
      (qRT-PCR) with improved sensitivity that detects as little as 1 * 10(-2)
      TCID50/ml of viral RNA. We tested serum samples collected in January and
      September 2008, October 2009 and January 2011 from a farm with an outbreak and
      found infected pigs between January and September 2008, but not in January 2011.
      Further, between 2008 and 2011, we did not detect infection in pigs at 8 nearby
      farms or in 2,052 serum samples collected from pigs from 74 farms in 12
      prefectures. This assay should help prevent future outbreaks. 

PMID- 25047906
TI  - Study of multi-level characteristics for 3D vertical resistive switching memory.
AB  - Three-dimensional (3D) integration and multi-level cell (MLC) are two attractive
      technologies to achieve ultra-high density for mass storage applications. In this
      work, a three-layer 3D vertical AlOdelta/Ta2O5-x/TaOy resistive random access
      memories were fabricated and characterized. The vertical cells in three layers
      show good uniformity and high performance (e.g. >1000X HRS/LRS windows, >10(10)
      endurance cycles, >10(4) s retention times at 125 degrees C). Meanwhile, four
      level MLC is demonstrated with two operation strategies, current controlled
      scheme (CCS) and voltage controlled scheme (VCS). The switching mechanism of 3D
      vertical RRAM cells is studied based on temperature-dependent transport
      characteristics. Furthermore, the applicability of CCS and VCS in 3D vertical
      RRAM array is compared using resistor network circuit simulation.

PMID- 25047907
TI  - Comparing moral judgments of patients with frontotemporal dementia and frontal
      stroke.
AB  - IMPORTANCE: Several clinical reports have stated that patients with prefrontal
      lesions or patients with the behavioral variant of frontotemporal dementia share
      social cognition impairments. Moral reasoning is impaired in both conditions but
      there have been few investigations that directly compare this domain in the 2
      groups. OBSERVATIONS: This work compared the moral judgments of these patient
      groups using a task designed to disentangle the contributions of intentions and
      outcomes in moral judgment. For both disorders, patients judged scenarios where
      the protagonists believed that they would cause harm but did not as being more
      permissible than the control group. Moreover, patients with frontotemporal
      dementia judged harmful outcomes in the absence of harmful intentions as less
      permissible than the control participants. There were no differences between the
      2 conditions. CONCLUSIONS AND RELEVANCE: Both disorders involved impairments in
      integrating intention and outcome information for moral judgment. This study was
      the first, to our knowledge, to directly compare a social cognition domain in 2
      frontal pathologies with different etiology. Our results highlighted the
      importance of comparing patients with vascular lesions and patients with
      neurodegenerative diseases.

PMID- 25047908
TI  - Ultrasound elastography in the early diagnosis of plantar fasciitis.
AB  - BACKGROUND: The purpose of this study was to investigate whether ultrasound (US)
      elastography is useful for the early diagnosis of plantar fasciitis. MATERIAL AND
      METHODS: We retrospectively reviewed US elastography findings of 18 feet with a
      clinical history and physical examination highly suggestive of plantar fasciitis
      but with normal findings on conventional US imaging as well as 18 asymptomatic
      feet. RESULT: Softening of the plantar fascia was significantly greater in the
      patient than in the control group [Reviewers 1 and 2: 89% (16/18) vs. 50% (9/18),
      P=.027, respectively]. CONCLUSION: US elastography is useful for the early
      diagnosis of plantar fasciitis.

PMID- 25047909
TI  - Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in
      amyotrophic lateral sclerosis (ALS).
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, responsible
      for the integrity of the basement membrane (BM) via degradation of extracellular
      matrix and BM components. These enzymes are presented in central and peripheral
      nervous system. They are considered to be involved in the pathogenesis of several
      neurological diseases, including amyotrophic lateral sclerosis (ALS). ALS is a
      motor neuron disease, leading to muscle atrophy, paralysis and death within 3-5
      years from diagnosis. Currently, there is no treatment that can substantially
      prolong life of ALS patients. Despite the fact that MMPs are not specific for
      ALS, there is also strong evidence that these enzymes are involved in the
      pathology of ALS. MMPs are able to exert direct neurotoxic effects, or may cause
      cell death by degrading matrix proteins. The objective of this paper is to
      provide an updated and comprehensive review concerning the role of MMPs and their
      tissue inhibitors (TIMPs) in the pathology of ALS with an emphasis on the
      significance of MMP-2 and MMP-9 as well as their tissue inhibitors as potential
      biomarkers of ALS. Numerous hypotheses have been proposed regarding the role of
      selected MMPs and TIMPs in ALS pathogenesis. Moreover, selective MMPs' inhibitors
      might be potential targets for therapeutic strategies for patients with ALS.
      However, future investigations are necessary before some of those non-specific
      for ALS enzymes could finally be used as biomarkers of this disease. 

PMID- 25047910
TI  - Impaired cognitive control in Parkinson's disease patients with freezing of gait
      in response to cognitive load.
AB  - Freezing of gait is a frequent and disabling symptom experienced by many patients
      with Parkinson's disease. A number of executive deficits have been shown to be
      associated with the phenomenon suggesting a common underlying pathophysiology,
      which as of yet remains unclear. Neuroimaging studies have also implicated the
      role of the cognitive control network in patients with freezing. To explore this
      concept, the current study examined error-monitoring as a measure of cognitive
      control. Thirty-four patients with and 38 without freezing of gait, who were
      otherwise well matched on disease severity, completed a colour-word interference
      task that allowed the specific assessment of error monitoring during conflict.
      Whilst both groups performed colour-naming and word-reading tasks equally well,
      those patients with freezing showed a pattern between conditions whereby they
      were better able to monitor performance and self-correct errors in the pure
      inhibition task but not after a switching rule was introduced. The novel results
      shown here provide insight into possible pathophysiological mechanisms involved
      in cognitive load and error monitoring in patients with freezing of gait. These
      results provide further evidence for the role of functional frontostriatal
      circuitry impairments in patients with freezing of gait and have implications for
      future studies and possible therapeutic interventions. 

PMID- 25047911
TI  - Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite
      phenotype based on genotype and comedications with CYP2D6 inhibitors.
AB  - The cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of most
      antidepressants. Comedication with a potent CYP2D6 inhibitor can convert patients
      with extensive metabolizer (EM) or ultra-rapid metabolizer (UM) genotypes into
      poor metabolizer (PM) phenotypes. Since comedication is frequent in depressed
      patients treated with antidepressants, we investigated the effect of the CYP2D6
      composite phenotype on antidepressant efficacy, taking into account both the
      CYP2D6 genotype and comedication with CYP2D6 inhibitors. 87 Caucasian in patients
      with a major depressive episode were prospectively treated with flexible doses of
      antidepressant monotherapy as well as comedications and genotyped for the major
      CYP2D6 alleles (CYP2D6*3 rs35742686, *4 rs3892097, *5 del, *6 rs5030655, and
      *2xN). They were classified for CYP2D6 composite phenotype and assessed for
      antidepressant response after 4 weeks. In terms of genotypes (g), 6 subjects were
      UMg, 6 PMg, and 75 EMg. Ten patients were coprescribed a CYP2D6 inhibitor,
      resulting in the following composite phenotypes (cp): 5 UMcp, 16 PMcp, and 66
      EMcp. Whereas none of the CYP2D6 genotypes were significantly associated with
      antidepressant response, UMcp had a lower antidepressant response than PMcp or
      EMcp (respectively: 39.0 +/- 17.9, 50.0 +/- 26.0, and 61.6 +/- 23.4, p = 0.02).
      Despite small sample size, this study suggests that a CYP2D6 composite phenotype,
      taking into account both genotype and comedications with CYP2D6 inhibitors, could
      predict CYP2D6 substrate antidepressants response. Thus, to optimize
      antidepressant response, CYP2D6 genotype could be performed and comedications
      with CYP2D6 inhibitors should be avoided, when prescribing CYP2D6 substrate
      antidepressants. 

PMID- 25047912
TI  - Phylogeography of Bacillus anthracis in the country of Georgia shows evidence of
      population structuring and is dissimilar to other regional genotypes.
AB  - Sequence analyses and subtyping of Bacillus anthracis strains from Georgia reveal
      a single distinct lineage (Aust94) that is ecologically established.
      Phylogeographic analysis and comparisons to a global collection reveals a clade
      that is mostly restricted to Georgia. Within this clade, many groups are found
      around the country, however at least one subclade is only found in the eastern
      part. This pattern suggests that dispersal into and out of Georgia has been rare
      and despite historical dispersion within the country, for at least for one
      lineage, current spread is limited. 

PMID- 25047913
TI  - Transcranial extracellular impedance control (tEIC) modulates behavioral
      performances.
AB  - Electric brain stimulations such as transcranial direct current stimulation
      (tDCS), transcranial random noise stimulation (tRNS), and transcranial
      alternating current stimulation (tACS) electrophysiologically modulate brain
      activity and as a result sometimes modulate behavioral performances. These
      stimulations can be viewed from an engineering standpoint as involving an
      artificial electric source (DC, noise, or AC) attached to an impedance branch of
      a distributed parameter circuit. The distributed parameter circuit is an
      approximation of the brain and includes electric sources (neurons) and impedances
      (volume conductors). Such a brain model is linear, as is often the case with the
      electroencephalogram (EEG) forward model. Thus, the above-mentioned current
      stimulations change the current distribution in the brain depending on the
      locations of the electric sources in the brain. Now, if the attached artificial
      electric source were to be replaced with a resistor, or even a negative resistor,
      the resistor would also change the current distribution in the brain. In light of
      the superposition theorem, which holds for any linear electric circuit, attaching
      an electric source is different from attaching a resistor; the resistor affects
      each active electric source in the brain so as to increase (or decrease in some
      cases of a negative resistor) the current flowing out from each source. From an
      electrophysiological standpoint, the attached resistor can only control the
      extracellular impedance and never causes forced stimulation; we call this
      technique transcranial extracellular impedance control (tEIC). We conducted a
      behavioral experiment to evaluate tEIC and found evidence that it had real-time
      enhancement and depression effects on EEGs and a real-time facilitation effect on
      reaction times. Thus, tEIC could be another technique to modulate behavioral
      performance. 

PMID- 25047914
TI  - Amphiphilic bicyclic peptides as cellular delivery agents.
AB  - Two bicyclic peptides composed of tryptophan and arginine residues were
      synthesized from monocyclic peptide building blocks and evaluated as cellular
      delivery agents. [W5G]-(triazole)-[KR5] and [W5E]-(beta-Ala)-[KR5] containing
      triazole and beta-alanine linkers improved the cellular delivery of fluorescein
      (F')-labeled phosphopeptide F'-GpYEEI (F'-PP) by 7.6- and 19.3-fold,
      respectively, in human ovarian adenocarcinoma cells. However, parent monocyclic
      peptide [R5 ] and monocyclic peptide [WR]4 only enhanced the cellular uptake of
      the phosphopeptide by only 1.3- and 3.7-fold, respectively. Confocal microscopy
      showed that the corresponding fluorescein-labeled bicyclic peptide F'-[KW4E]
      (beta-Ala)-[KR5] was localized in the cytosol and nucleus. Studying the cellular
      uptake of F'-[KW4E]-(beta-Ala)-[KR5] in the presence of endocytosis inhibitors
      indicated that the clathrin- and caveolin-dependent endocytosis are the main
      pathways for cellular uptake. The bicyclic peptide was able to improve
      antiproliferative activity of doxorubicin by 20 %. These data suggest that this
      bicyclic peptide can be utilized as a new class of cell-penetrating peptides and
      cellular delivery tools.

PMID- 25047916
TI  - Model-wise and point-wise random sample consensus for robust regression and
      outlier detection.
AB  - Popular regression techniques often suffer at the presence of data outliers. Most
      previous efforts to solve this problem have focused on using an estimation
      algorithm that minimizes a robust M-estimator based error criterion instead of
      the usual non-robust mean squared error. However the robustness gained from M
      estimators is still low. This paper addresses robust regression and outlier
      detection in a random sample consensus (RANSAC) framework. It studies the
      classical RANSAC framework and highlights its model-wise nature for processing
      the data. Furthermore, it introduces for the first time a point-wise strategy of
      RANSAC. New estimation algorithms are developed following both the model-wise and
      point-wise RANSAC concepts. The proposed algorithms' theoretical robustness and
      breakdown points are investigated in a novel probabilistic setting. While the
      proposed concepts and algorithms are generic and general enough to adopt many
      regression machineries, the paper focuses on multilayered feed-forward neural
      networks in solving regression problems. The algorithms are evaluated on
      synthetic and real data, contaminated with high degrees of outliers, and compared
      to existing neural network training algorithms. Furthermore, to improve the time
      performance, parallel implementations of the two algorithms are developed and
      assessed to utilize the multiple CPU cores available on nowadays computers. 

PMID- 25047917
TI  - Pharmacokinetics and tissue distribution of pterostilbene in the rat.
AB  - SCOPE: Pterostilbene (Pt) is emerging as an important health-promoting natural
      compound. Pharmacokinetic studies so far have focused on plasma levels, while Pt
      distribution in tissues is most relevant for biological action. This study
      determined tissue distribution of Pt and its major metabolite, pterostilbene-4'
      sulfate (Pt-S), in rats after oral administration. METHODS AND RESULTS: Upon
      intravenous (iv) administration (88 MUmol/kg), Pt was cleared from blood with a
      half-life of 1.8 +/- 0.3 h. Oral administration (same dose) resulted in moderate
      Pt bioavailability (~35%) and in an increased abundance of Pt-S in blood
      (AUC(Pt)/AUC(Pt-S) ~0.75 and ~0.05 after iv or oral administration,
      respectively). Pt-S was the major species in all organs except the brain, where
      intact Pt was predominant (AUC(Pt)/AUC(Pt-S) ~5). Both Pt and Pt-S peaked in all
      tissues at approximately 2 h. The highest levels (~200 nmoles/g for Pt-S and 40
      nmoles/g for Pt) were measured in the liver, the lowest (<=7 nmol/g) in skeletal
      muscles and testes. CONCLUSION: AUC(Pt) was ~2- to ~25-fold higher in tissues
      than in blood; this may explain its bioactivity despite barely detectable blood
      levels. Of particular interest is the high fraction of nonmetabolized Pt in the
      brain, given the reports of its activity at the level of the central nervous
      system.

PMID- 25047919
TI  - Hazardous birthday drinking among young people: population-based impacts on
      emergency department and in-patient hospital admissions.
AB  - BACKGROUND AND AIMS: There is growing concern about the possible adverse health
      impacts of binge drinking during birthday celebrations among adolescents and
      young adults. We estimate the impacts of birthday alcohol use on adolescent and
      young adult in-patient/emergency department (ED) hospital admissions. DESIGN: We
      employed Autoregressive Integrated Moving Average (ARIMA) intervention analysis
      to assess whether the rate of ICD-10 alcohol-use-disorder (AUD) events per 1000
      in-patient/ED admissions increased significantly during birthday weeks. SETTING:
      All in-patient/ED admissions in Ontario, Canada from 1 April 2002 to 31 March
      2007. PARTICIPANTS: Individuals aged 12-30 years. MEASUREMENTS: AUD events per
      1000 in-patient/ED admissions by age in weeks. FINDINGS: Multiple increases were
      found. The largest occurred during the birthday week of 19 years of age, the
      beginning of the minimum legal drinking age (MLDA) in Ontario: AUD admission
      rates increased (spiked) by 38.30 per 1000 total admissions [95% confidence
      interval (CI) = 34.66-41.94] among males (a 114.3% increase over baseline), and
      by 28.13 (95% CI = 25.56-30.70) among females (a 164.0% increase). Among both
      genders, the second largest birthday-week spikes occurred during ages 20-22
      years, followed by somewhat lower but still pronounced birthday-week spikes
      during ages 23-26 years and 30 years (all these spikes: P < 0.05). Birthday-week
      spikes occurred as early as age 16 years for males and 14 years for females (both
      spikes: P < 0.05). CONCLUSIONS: There appears to be an increase in alcohol
      related adverse events from drinking around the time of one's birthday among
      young adults in Canada.

PMID- 25047918
TI  - Human stefin B role in cell's response to misfolded proteins and autophagy.
AB  - Alternative functions, apart from cathepsins inhibition, are being discovered for
      stefin B. Here, we investigate its role in vesicular trafficking and autophagy.
      Astrocytes isolated from stefin B knock-out (KO) mice exhibited an increased
      level of protein aggregates scattered throughout the cytoplasm. Addition of
      stefin B monomers or small oligomers to the cell medium reverted this phenotype,
      as imaged by confocal microscopy. To monitor the identity of proteins embedded
      within aggregates in wild type (wt) and KO cells, the insoluble cell lysate
      fractions were isolated and analyzed by mass spectrometry. Chaperones, tubulins,
      dyneins, and proteosomal components were detected in the insoluble fraction of wt
      cells but not in KO aggregates. In contrast, the insoluble fraction of KO cells
      exhibited increased levels of apolipoprotein E, fibronectin, clusterin, major
      prion protein, and serpins H1 and I2 and some proteins of lysosomal origin, such
      as cathepsin D and CD63, relative to wt astrocytes. Analysis of autophagy
      activity demonstrated that this pathway was less functional in KO astrocytes. In
      addition, synthetic dosage lethality (SDL) gene interactions analysis in
      Saccharomyces cerevisiae expressing human stefin B suggests a role in transport
      of vesicles and vacuoles These activities would contribute, directly or
      indirectly to completion of autophagy in wt astrocytes and would account for the
      accumulation of protein aggregates in KO cells, since autophagy is a key pathway
      for the clearance of intracellular protein aggregates. 

PMID- 25047920
TI  - Predictive factor of local recurrence after balloon-occluded TACE with miriplatin
      (MPT) in hepatocellular carcinoma.
AB  - BACKGROUND: Miriplatin (MPT) is a novel platinum complex used in TACE that shows
      promise for the treatment of hepatocellular carcinoma (HCC). However, rapid
      washout has been reported in some cases. Therefore, various methods of
      administration with MPT have been attempted to increase its therapeutic efficacy.
      One hopeful method is balloon-occluded TACE (B-TACE), but the therapeutic
      efficacy of B-TACE with MPT has not been evaluated. AIM: To investigate the
      treatment outcomes and factors involved in local recurrence after B-TACE with MPT
      in HCC. METHODS: This study included 51 patients (55 nodules) with HCC lesions
      equal or less than 5 cm in diameter who underwent B-TACE with MPT between January
      2012 and June 2013. Local recurrence after B-TACE with MPT and factors associated
      with local recurrence were evaluated. RESULTS: The overall local recurrence rate
      was 11.1% at 6 months and 26.2% at 12 months. The local recurrence rate did
      differ significantly depending on CT values immediately after B-TACE with MPT.
      Multivariate analysis also showed that the CT value after B-TACE with MPT was the
      only factor related to local recurrence after B-TACE. CONCLUSIONS: B-TACE with
      MPT achieves relatively good local control of HCC. The plain CT value immediately
      after B-TACE with MPT is a predictive factor for local recurrence. In patients
      with unsatisfactory CT values, locoregional therapy or additional treatment is
      required.

PMID- 25047921
TI  - Cystic tumor of the liver without ovarian-like stroma or bile duct communication:
      two case reports and a review of the literature.
AB  - We report two cases of cystic neoplasm of the liver with mucinous epithelium in
      which both ovarian-like stroma and bile duct communication were absent. The first
      case was a 41-year-old woman. She underwent right trisegmentectomy due to a
      multilocular cystic lesion, 15 cm in diameter, with papillary nodular components
      in the medial segment and right lobe. Histologically, arborizing papillae were
      seen in the papillary lesion. The constituent neoplastic cells had sufficient
      cytoarchitectural atypia to be classified as high-grade dysplasia. The second
      case was a 60-year-old woman. She underwent left lobectomy due to a unilocular
      cystic lesion, 17 cm in diameter, in the left lobe. Histologically, the cyst wall
      was lined by low columnar epithelia with slight cellular atypia. In both cases,
      neither ovarian-like stroma nor bile duct communications were found throughout
      the resected specimen. According to the most recent World Health Organization
      (WHO) classification in 2010, cystic tumors of the liver with mucinous epithelium
      are classified as mucinous cystic neoplasms when ovarian-like stromata are found,
      and as intraductal papillary neoplasm of bile duct when bile duct communication
      exists. Therefore, we diagnosed the cystic tumors as 'biliary cystadenoma'
      according to the past WHO classification scheme from 2000. We believe that the
      combined absence of both ovarian-like stroma and bile duct communication is
      possible in mucinous cystic tumors of the liver. Herein, we have described the
      clinicopathologic features of the two cases and reviewed past cases in the
      literature. 

PMID- 25047922
TI  - Mycobacterium marinum infection in Japanese forest green tree frogs (Rhacophorus
      arboreus).
AB  - Four Japanese forest green tree frogs (Rhacophorus arboreus) were presented with
      emaciation, abdominal distention and ulcerative and nodular cutaneous lesions
      affecting the brisket, limbs, digits and ventral abdomen. Another three frogs had
      been found dead in the same tank 1 year previously. Necropsy examination of these
      seven frogs revealed splenomegaly and hepatomegaly, with multiple tan-yellow
      nodular foci present in the liver, spleen, heart, lungs, ovaries and kidneys.
      Microscopically, five frogs had necrosis and surrounding granulomatous
      inflammation in the liver, spleen, kidneys, lungs, intestine and ovaries, with
      numerous acid-fast bacilli in the areas of necrosis. Two frogs had granulomatous
      lesions in the lungs, liver, spleen, heart, coelomic membrane, stomach and
      intestinal wall. These lesions had no or minimal necrosis and few acid-fast
      bacilli. Mycobacterium spp. was cultured from three frogs and identified as
      Mycobacterium marinum by colony growth rate and photochromogenicity and DNA
      sequencing. This is the first report of M. marinum infection in Japanese forest
      green tree frogs.

PMID- 25047923
TI  - Absent right and persistent left superior vena cava: troubleshooting during a
      challenging pacemaker implant: a case report.
AB  - BACKGROUND: Venous anomalies of the thorax can occur in isolation or in
      association with complex congenital heart disease. The incidence of an absent
      right superior vena cava in the setting of a persistent left superior vena cava
      is very rare in the general population with only a dozen cases documented in the
      medical literature. Such venous anomalies can make for very challenging
      electronic cardiac device implantation. We report our challenging dual chamber
      pacemaker implant in a patient with such complex anatomy and focus on our
      implantation technique that helped achieve adequate lead positioning. CASE
      PRESENTATION: A 73-year-old Caucasian female with degenerative complete heart
      block presented for dual chamber permanent pacemaker implant. Lead implantation
      was very challenging due to abnormal and rare vena cava anatomy; a persistent
      left superior vena cava drained directly into the coronary sinus and the right
      brachiocephalic vein drained directly into the left persistent superior vena cava
      as the patient had an absent right superior vena cava . Adequate right
      ventricular lead positioning was achieved following numerous lead-stylet
      manipulations and careful looping in the atria to redirect its trajectory to the
      ventricular apex. CONCLUSION: Abnormal superior vena cava development is uncommon
      and can lead to technical challenges when venous access is required during
      various interventional procedures. Pre-operative imaging can help identify such
      challenging anatomy allowing appropriate operative planning; careful patient
      selection is warranted for venography given the risk of contrast nephrotoxicity.

PMID- 25047924
TI  - Ghost cells in pilomatrixoma, craniopharyngioma, and calcifying cystic
      odontogenic tumor: histological, immunohistochemical, and ultrastructural study.
AB  - BACKGROUND: Pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic
      tumor are the main entities presenting ghost cells as an important histological
      feature, in spite their quite different clinical presentation; it seems that they
      share a common pathway in the formation of these cells. The aim of this study is
      to examine and compare the characteristics of ghost and other cells that form
      these lesions. METHODS: Forty-three cases including 21 pilomatrixomas, 14
      craniopharyngiomas, and eight calcifying cystic odontogenic tumors were evaluated
      by immunohistochemistry for cytokeratins, CD138, beta-catenin, D2-40, Glut-1,
      FAS, CD10 and also by scanning electron microscopy. RESULTS: The CKs, CD138, beta
      catenin, Glut-1, FAS, and CD10 were more often expressed by transitional cells of
      craniopharyngioma and calcifying cystic odontogenic tumor, compared with
      pilomatrixoma. Basaloid cells of pilomatrixoma showed strong positivity for CD138
      and CD10. Differences on expression pattern were identified in transitional and
      basal cells, as ghost cells were negative for most antibodies used, except by low
      expression for cytokeratins. By scanning electron microscopy, the morphology of
      ghost cells were similar in their fibrillar cytoplasm, but their pattern varied
      from sheets in pilomatrixoma to small clusters in craniopharyngioma and
      calcifying cystic odontogenic tumor. CONCLUSIONS: Mechanisms involved in
      formation of ghost cells are unknown, but probably they follow different pathways
      as protein expression in the basal/transitional cells was not uniform in the
      three tumors studied.

PMID- 25047925
TI  - Confounders of mortality and hospitalization rate calculations for profit and
      nonprofit dialysis facilities: analytic augmentation.
AB  - BACKGROUND: Patient outcomes have been compared on the basis of the profit status
      of the dialysis provider (for-profit [FP] and not-for-profit [NFP]). In its
      annual report, United States Renal Data System (USRDS) provides dialysis provider
      level death and hospitalization rates adjusted by age, race, sex, and dialysis
      vintage; however, recent analyses have suggested that other variables impact
      these outcomes. Our current analysis of hospitalization and mortality rates of
      hemodialysis patients included adjustments for those used by the USRDS plus other
      potential confounders: facility geography (end-stage renal disease network),
      length of facility ownership, vascular access at first dialysis session, and pre
      dialysis nephrology care. METHODS: We performed a provider level, retrospective
      analysis of 2010 hospitalization and mortality rates among US hemodialysis
      patients exclusively using USRDS sources. Crude and adjusted incidence rate
      ratios (IRRs) were calculated using the 4 standard USRDS patient factors plus the
      4 potential confounders noted above. RESULTS: The analysis included 366,011 and
      34,029 patients treated at FP and NFP facilities, respectively. There were
      statistical differences between the cohorts in geography, facility length of
      ownership, vascular access, and pre-dialysis nephrology care (p < 0.001), as well
      as age (p < 0.01), race (p < 0.001), and vintage (p < 0.001), but not sex (p =
      0.12). When using standard USRDS adjustments, hospitalization and mortality rates
      for FP and NFP facilities were most disparate, favoring the NFP facilities. Rates
      were most similar between providers when adjustments were made for each of the 8
      factors. With the FP IRR as the referent (1.0), the hospitalization IRR for NFP
      facilities was 1.00 (95% confidence interval [CI] 0.97-1.02; p = 0.69), while the
      NFP mortality IRR was 1.01 (95% CI 0.97-1.05; p = 0.64). CONCLUSIONS: These data
      suggest there is no difference in mortality and hospitalization rates between FP
      and NFP dialysis clinics when appropriate statistical adjustments are made.

PMID- 25047926
TI  - "Expanding" the scope of practice of dental medicine for tomorrow's dental
      graduate: a unique role for our combined specialties.

PMID- 25047927
TI  - Predictability and accuracy of maxillary repositioning during bimaxillary surgery
      using a three-dimensional positioning technique.
AB  - OBJECTIVE: The purpose of this retrospective study was to evaluate the
      predictability and accuracy of maxillary repositioning during bimaxillary surgery
      using a three-dimensional positioning technique. STUDY DESIGN: Twenty-six adult
      patients who underwent bimaxillary surgery requiring high superior maxillary
      impactions were divided into 2 groups. In group A, a three-dimensional
      positioning technique during maxillary repositioning was used along with an
      intermediate occlusal splint. In group B, only an intermediate occlusal splint
      with internal reference points was used. Both groups had measurements from
      predictive tracings compared to postoperative cephalograms to assess the accuracy
      of horizontal and vertical movements of the maxilla. RESULTS: Group A showed
      excellent correlation between the planned and actual maxillary positions in
      vertical and horizontal dimensions. In group B, the maxilla tended to move
      anteriorly than planned. CONCLUSIONS: Use of the three-dimensional positioning
      technique offered a predictive and accurate method for maxillary repositioning.

PMID- 25047928
TI  - Dental treatment in the cardiothoracic intensive care unit for patients with
      ventricular assist devices awaiting heart transplant: a case series.
AB  - OBJECTIVE: This report aims to describe the dental protocol for treating in the
      intensive care unit patients with end-stage heart failure who have had
      ventricular assist devices (VADs) emergently implanted as a bridge to heart
      transplant. This protocol permitted the rendering of safe and effective dental
      care in this setting and did not result in near-term (1-30 days) excessive
      hemorrhage, local and systemic infection, or contamination of the VAD. STUDY
      DESIGN: This descriptive cross-sectional study by the University of California,
      Los Angeles, Hospital Dental Service examined the dental care of 9 patients (mean
      age, 50 +/- 12.9 years) with class IV stage D heart failure. RESULTS: Nine
      patients, 22 days (mean) after VAD placement, received dental treatment after
      intravenous prophylactic antibiotics and maintenance of prior anticoagulation,
      antiplatelet, or antithrombin regimen. Eight patients had extractions (mean, 4;
      range, 1-12), and one of them also required scaling and root planing (SRP) of the
      remaining teeth. A ninth individual only required SRP of 4 quadrants. No adverse
      outcomes developed. CONCLUSIONS: Emergent removal of active dental disease in
      patients with VAD awaiting heart transplant can be safely accomplished using
      established protocols with extended vigilance.

PMID- 25047929
TI  - Osteonecrosis of the jaw in patients treated with oral and intravenous
      bisphosphonates: experience in Sweden.
AB  - OBJECTIVE: To describe the prevalence, inciting factors, and treatment outcomes
      of bisphosphonate-related osteonecrosis of the jaw (BRONJ) during the 2003-2010
      period in southern Sweden (population, approximately 1.2 million people). STUDY
      DESIGN: Patient records were searched for inflammatory conditions including
      unspecified inflammation, osteomyelitis, osteonecrosis due to drugs, and other
      osteonecrosis. Data on underlying disease, type of bisphosphonate (BP), inciting
      factor, location, stage, treatment, and treatment outcomes were collected.
      RESULTS: Of the 341 patients identified, 55 had been diagnosed with BRONJ. Those
      with a malignant disease were treated with intravenous BPs, and those with
      osteoporosis were treated with oral BPs. All but 5 were treated with antibiotics
      and 47 with local resection. Healing was recorded in 79% of patients with
      osteoporosis and in 26% of patients with malignant disease. CONCLUSIONS: Healing
      in patients with osteoporosis occurred more frequently than in patients with a
      malignant disease treated with intravenous BPs (P = .00009).

PMID- 25047930
TI  - Resorbable collagen membranes: histopathologic features.
AB  - OBJECTIVE: Resorbable collagen membranes (RCMs) are commonly used by oral
      surgeons, periodontists, and endodontists for multiple purposes. We report 6
      cases of RCMs that did not resorb as expected and describe the histopathologic
      features. STUDY DESIGN: Cases of an unusual fibrillar foreign material were noted
      in biopsy specimens curetted from bone. Hematoxylin-eosin and Masson trichrome
      stains were performed. Clinicians were contacted for detailed clinical
      information. RESULTS: There were 3 men and 3 women. RCMs presented as hyalinized,
      paucicellular, delicate eosinophilic fibrils or a meshwork without a foreign body
      reaction. They were refractile and stained for Masson trichrome as expected.
      These RCMs persisted longer than expected (2-6 weeks) in 3 cases and may have
      retarded healing in 5 cases. CONCLUSIONS: Although RCM is supposed to be fairly
      rapidly resorbable, this material sometimes persists within wound sites without
      any obvious foreign body reaction and may retard healing.

PMID- 25047931
TI  - Role of perfusion computed tomography in assessing submandibular gland
      radiochemotherapy-induced injury.
AB  - OBJECTIVE: We aimed to detect changes in the volume and perfusion parameters of
      the submandibular glands during and after radiochemotherapy. STUDY DESIGN: Twelve
      patients underwent computed tomography (CT) and perfusion CT before
      radiochemotherapy, after 40 Gy, after 70 Gy, and 3 months after
      radiochemotherapy. Submandibular gland volume, blood volume, permeability surface
      area product, and blood flow were quantified. RESULTS: Submandibular gland
      volumes during and after therapy were significantly lower compared with the
      baseline value (P < .001). Blood volume, blood flow, and permeability surface
      area product values showed statistically significant reduction during and 3
      months after therapy. A significant linear correlation was found between changes
      in submandibular gland volume and of the perfusion parameter blood volume in the
      period between baseline and 3 months after therapy (P = .012; RP = -0.697).
      CONCLUSIONS: Changes in submandibular gland volume and dynamics of perfusion
      parameters imply that radiation-induced injury of submandibular glands develops
      early during radiochemotherapy.

PMID- 25047932
TI  - Surface electromyography and magnetic resonance imaging of the masticatory
      muscles in patients with arthrogenous temporomandibular disorders.
AB  - OBJECTIVE: The purpose of this study was to verify the characteristics of surface
      electromyography (sEMG) of masticatory muscles in patients with temporomandibular
      disorders (TMDs) with differing pathology. STUDY DESIGN: A total of 24 patients
      with TMDs were categorized according to the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD); magnetic resonance imaging (MRI)
      classified the patients as having disk displacement alone (DD) (mean age, 22
      years; SD, 5; 3 men, 6 women) or having osteoarthrosis with or without disk
      displacement (OA) (mean age, 37 years; SD, 10; 4 men, 11 women); sEMG was
      performed according to a standardized protocol. RESULTS: The MRI score was
      significantly correlated to the torque coefficient (r = 0.57) and the temporalis
      (r = 0.85) and masseter (r = 0.46) muscle standardized symmetry. The
      discriminating ability of participant age and sEMG scores in separating the 2
      groups was assessed by receiver operating characteristic analysis. Each of the
      sEMG scores showed a significant ability in discriminating between osteoarthrosis
      and disk displacement. CONCLUSIONS: The recording of the masticatory muscle
      function through sEMG can be a first diagnostic approach to patients with TMDs,
      reserving MRI assessment to selected cases.

PMID- 25047933
TI  - Methotrexate pharmacotherapy for implant-related temporomandibular joint pain: a
      case report.
AB  - This article presents a patient experiencing several years of pain associated
      with bilateral failed temporomandibular joint (TMJ) Proplast/Teflon fossa
      prostheses. Despite surgical removal of the prostheses and comprehensive
      conservative management, including typical pharmacotherapy approaches for chronic
      pain, pain was still not relieved, and management was revised to target a
      putative chronic inflammatory disorder. Methotrexate was prescribed because of
      its known efficacy for inflammation and pain reduction in rheumatoid arthritis.
      Titration of methotrexate dosage over 5 months to a weekly dose of 20 mg resulted
      in reduced pain intensity at rest, increased pain-free maximal jaw opening, and a
      reduction in the sensory component of the McGill Pain Questionnaire. Maximum
      assisted jaw opening remained the same, as did the palpation tenderness of both
      TMJs and of the masseter and temporalis muscles. Methotrexate pharmacotherapy may
      represent a viable option when conservative treatments have failed to provide
      significant pain relief in patients who have had Proplast/Teflon TMJ implants. 

PMID- 25047934
TI  - Generalized odontodysplasia in a 5-year-old patient with Hallermann-Streiff
      syndrome: clinical aspects, cone beam computed tomography findings, and
      conservative clinical approach.
AB  - This article aims to report the main clinical aspects, cone beam computed
      tomography (CBCT) findings, and conservative oral rehabilitation in a child born
      from a consanguineous marriage who presented with Hallermann-Streiff syndrome
      (HSS) and generalized odontodysplasia. A 5-year-old girl presented with a
      diagnosis of HSS for oral evaluation. Radiographically, all teeth showed wide
      pulp chambers and roots with thin dentinal walls and open apices, resembling
      ghost teeth and indicating a diagnosis of odontodysplasia. Oral rehabilitation
      consisted of partial dentures that were regularly adjusted to conform the device
      with the pattern of growth and development of the child. CBCT scan provided great
      insight into HSS, allowing a detailed view of the morphologic aspects and
      associated trabecular bone pattern. Treatment of these 2 rare conditions in young
      children must consider the stage of growth and development. Although extremely
      rare in HSS, odontodysplasia should be investigated and conservatively managed in
      young children. 

PMID- 25047935
TI  - Design of granulatimide and isogranulatimide analogues as potential Chk1
      inhibitors: Study of amino-platforms for their synthesis.
AB  - The two marine alkaloids granulatimide and isogranulatimide have been shown to
      inhibit the checkpoint kinase 1 (Chk1), a promising target for cancer treatment.
      A molecular docking study allowing the design of new potential Chk1 inhibitors
      based on the natural products skeleton and the synthetic work to an amino-target
      platform to prepare them are described. 

PMID- 25047936
TI  - Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors
      with 'inverted' binding mode.
AB  - Selective and nanomolar acetylcholinesterase inhibitors were obtained by
      connecting tri- and tetracyclic quinazolinones-previously described as moderately
      active and unselective cholinesterase (ChE) inhibitors-via a hydroxyl group in
      para position to an anilinic nitrogen with different amines linked via a three
      carbon atom spacer. These tri- and tetracyclic quinazolinones containing
      different alicyclic ring sizes and connected to tertiary amines were docked to a
      high-resolution hAChE crystal structure to investigate the preferred binding mode
      in relation to results obtained by experimental structure-activity relationships.
      While the 'classical orientation' locating the heterocycle in the active site was
      rarely found, an alternative binding mode with the basic aliphatic amine in the
      active center ('inverted' orientation) was obtained for most compounds. Analyses
      of extended SARs based on this inverted binding mode are able to explain the
      compounds' binding affinities at AChE. 

PMID- 25047937
TI  - Antinociceptive and antidepressant-like action of endomorphin-2 analogs with
      proline surrogates in position 2.
AB  - In our efforts to develop new candidate drugs with antinociceptive and/or
      antidepressant-like activity, two novel endomorphin-2 (EM-2, Tyr-Pro-Phe-Phe-NH2)
      analogs, containing proline surrogates in position 2 were synthesized using
      commercially available racemic trans-4-phenylpyrrolidine-3-carboxylic acid (4-Ph
      beta-Pro). The obtained mixture of two diastereoisomeric peptides (2a and 2b) was
      separated by HPLC and both enantiopure analogs were used in the in vitro and in
      vivo studies. To assign the absolute configuration to the 4-Ph-beta-Pro residues
      in both peptides, the stereoselective synthesis of (3R,4S)-4-phenylpyrrolidine-3
      carboxylic acid was performed and this enantiomer was introduced into position 2
      of EM-2 sequence. Based on the HPLC retention times we were able to assign the
      absolute configuration of 4-Ph-beta-Pro residues in both peptide analogs. Analog
      2a incorporating (3R,4S)-4-Ph-beta-Pro residue produced strong analgesia in mice
      after intracerebroventricular (icv) administration which was antagonized by the
      MU-opioid receptor (MOR) antagonist, beta-funaltrexamine (beta-FNA). This analog
      also influenced an emotion-related behavior of mice, decreasing immobility time
      in the forced swimming and tail suspension tests, without affecting locomotor
      activity. The antidepressant-like effect was reversed by the delta-selective
      antagonist, naltrindole (NLT) and kappa-selective nor-binaltorphimine (nor-BNI).
      Thus, the experiments with selective opioid receptor antagonists revealed that
      analgesic action of analog 2a was mediated through the MOR, while the delta- and
      kappa-receptors (DOR and KOR, respectively) were engaged in the antidepressant
      like activity. Analog 2b with (3S,4R)-4-Ph-beta-Pro in position 2 showed no
      antinociceptive or antidepressant-like activity in animal studies. 

PMID- 25047938
TI  - Taxanes with high potency inducing tubulin assembly overcome tumoural cell
      resistances.
AB  - We have found that four taxanes with chemical modifications at positions C10 and
      C13 were active against all types of taxane resistant cell lines, resistant by P
      gp overexpression, by mutations in the beta-tubulin binding site or by
      overexpression of the highly dynamic betaIII-tubulin isotype. We have
      characterized the interaction of taxanes with high activity on chemotherapy
      resistant tumoural cells with microtubules, and also studied their cellular
      effects. The biochemical property enhanced in comparison with other taxanes is
      their potency at inducing tubulin assembly, despite the fact that their
      interactions with the microtubule binding sites (pore and luminal) are similar as
      studied by NMR and SAXS. A differential interaction with the S7-S9 loop (M-loop)
      is responsible for their enhanced assembly induction properties. The chemical
      changes in the structure also induce changes in the thermodynamic properties of
      the interaction, indicating a higher hydrophilicity and also explaining their
      properties on P-gp and betaIII overexpressing cells and on mutant cells. The
      effect of the compounds on the microtubular network is different from those
      observed with the classical (docetaxel and paclitaxel) taxanes, inducing
      different bundling in cells with microtubules being very short, indicating a very
      fast nucleation effect and reflecting their high assembly induction power. 

PMID- 25047939
TI  - Synthesis of fluorinated agonist of sphingosine-1-phosphate receptor 1.
AB  - The bioactive metabolite sphingosine-1-phosphate (S1P), a product of sphingosine
      kinases (SphKs), mediates diverse biological processes such as cell
      differentiation, proliferation, survival and angiogenesis. A fluorinated analogue
      of S1P receptor agonist has been synthesized by utilizing a ring opening reaction
      of oxacycles by a lithiated difluoromethylphosphonate anion as the key reaction.
      In vitro activity of this S1P analogue is also reported. 

PMID- 25047940
TI  - Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione
      derivatives as eEF-2K inhibitors.
AB  - A small molecule library of pyrido[2,3-d]pyrimidine-2,4-dione derivatives 6-16
      was synthesized from 6-amino-1,3-disubstituted uracils 18, characterized, and
      screened for inhibitory activity against eukaryotic elongation factor-2 kinase
      (eEF-2K). To understand the binding pocket of eEF-2K, structural modifications of
      the pyrido[2,3-d]pyrimidine were made at three regions (R(1), R(2), and R(3)). A
      homology model of eEF-2K was created, and compound 6 (A-484954, Abbott
      laboratories) was docked in the catalytic domain of eEF-2K. Compounds 6
      (IC50=420nM) and 9 (IC50=930nM) are found to be better molecules in this
      preliminary series of pyrido[2,3-d]pyrimidine analogs. eEF-2K activity in MDA-MB
      231 breast cancer cells is significantly reduced by compound 6, to a lesser
      extent by compound 9, and is unaffected by compound 12. Similar inhibitory
      results are observed when eEF-2K activity is stimulated by 2-deoxy-d-glucose (2
      DOG) treatment, suggesting that compounds 6 and 9 are able to inhibit AMPK
      mediated activation of eEF-2K to a notable extent. The results of this work will
      shed light on the further design and optimization of novel pyrido[2,3
      d]pyrimidine analogs as eEF-2K inhibitors. 

PMID- 25047941
TI  - Apoptosis-inducing effect of a palladium(II) saccharinate complex of terpyridine
      on human breast cancer cells in vitro and in vivo.
AB  - The anti-growth effect of a palladium(II) complex-[PdCl(terpy)](sac).2H2O]
      (sac=saccharinate, and terpy=2,2':6',2"-terpyridine)-was tested against human
      breast cancer cell lines, MCF-7 and MDA-MB-231. Anti-growth effect was assayed by
      the MTT and ATP viability assays in vitro and then confirmed on Balb/c mice in
      vivo. The mode of cell death was determined by both histological and biochemical
      methods. The Pd(II) complex had anti-growth effect on a dose dependent manner in
      vitro and in vivo. The cells died by apoptosis as evidenced by the pyknotic
      nucleus, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active
      caspase-3. These results suggest that the palladium(II) saccharinate complex of
      terpyridine represents a potentially active novel complex for the breast cancer
      treatment, thus warrants further studies. 

PMID- 25047946
TI  - Abnormal interactions between context, memory structure, and mood in
      schizophrenia: an ERP investigation.
AB  - This study used event-related potentials to examine interactions between mood,
      sentence context, and semantic memory structure in schizophrenia. Seventeen male
      chronic schizophrenia and 15 healthy control subjects read sentence pairs after
      positive, negative, or neutral mood induction. Sentences ended with expected
      words (EW), within-category violations (WCV), or between-category violations
      (BCV). Across all moods, patients showed sensitivity to context indexed by
      reduced N400 to EW relative to both WCV and BCV. However, they did not show
      sensitivity to the semantic memory structure. N400 abnormalities were
      particularly enhanced under a negative mood in schizophrenia. These findings
      suggest abnormal interactions between mood, context processing, and connections
      within semantic memory in schizophrenia, and a specific role of negative mood in
      modulating semantic processes in this disease. 

PMID- 25047945
TI  - Whole-exome sequencing reveals overlap between macrophage activation syndrome in
      systemic juvenile idiopathic arthritis and familial hemophagocytic
      lymphohistiocytosis.
AB  - OBJECTIVE: Macrophage activation syndrome (MAS), a life-threatening complication
      of systemic juvenile idiopathic arthritis (JIA), resembles familial
      hemophagocytic lymphohistiocytosis (HLH), a constellation of autosomal-recessive
      immune disorders resulting from deficiency in cytolytic pathway proteins. We
      undertook this study to test our hypothesis that MAS predisposition in systemic
      JIA could be attributed to rare gene sequence variants affecting the cytotolytic
      pathway. METHODS: Whole-exome sequencing was used in 14 patients with systemic
      JIA and MAS and in their parents to identify protein-altering single-nucleotide
      polymorphisms/indels in known HLH-associated genes. To discover new candidate
      genes, the entire whole-exome sequencing data were filtered to identify protein
      altering, rare recessive homozygous, compound heterozygous, and de novo variants
      with the potential to affect the cytolytic pathway. RESULTS: Heterozygous protein
      altering rare variants in the known genes (LYST,MUNC13-4, and STXBP2) were found
      in 5 of 14 patients with systemic JIA and MAS (35.7%). This was in contrast to
      only 4 variants in 4 of 29 patients with systemic JIA without MAS (13.8%).
      Homozygosity and compound heterozygosity analysis applied to the entire whole
      exome sequencing data in systemic JIA/MAS revealed 3 recessive pairs in 3 genes
      and compound heterozygotes in 73 genes. We also identified 20 heterozygous rare
      protein-altering variants that occurred in at least 2 patients. Many of the
      identified genes encoded proteins with a role in actin and microtubule
      reorganization and vesicle-mediated transport. "Cellular assembly and
      organization" was the top cellular function category based on Ingenuity Pathways
      Analysis (P < 3.10 * 10(-5) ). CONCLUSION: Whole-exome sequencing performed in
      patients with systemic JIA and MAS identified rare protein-altering variants in
      known HLH-associated genes as well as in new candidate genes.

PMID- 25047947
TI  - Factors affecting receipt of expensive cancer treatments and mortality: evidence
      from stem cell transplantation for leukemia and lymphoma.
AB  - OBJECTIVE: To identify factors that affect whether patients diagnosed with either
      leukemia or lymphoma receive a stem cell transplant and secondly if receipt of
      stem cell transplantation is linked to improved survival. DATA: California
      inpatient discharge records (2002-2003) for patients with either leukemia or
      lymphoma linked with vital statistics death records (2002-2005). STUDY DESIGN:
      Bivariate Probit treatment effects model that accounts for both the type of
      treatment received and survival while controlling for nonrandom selection due to
      unobservable factors. PRINCIPAL FINDINGS: Having private insurance coverage and
      residence in a well-educated county increased the chances a patient with either
      disease received HSCT. Increasing age and travel distance to the nearest
      transplant hospital had the opposite effect. Receipt of HSCT had a significant
      impact on mortality. We found the probability of death was 4.3 percentage points
      higher for leukemia patients who did NOT have HSCT. Receipt of HSCT reduced the
      chances of dying by almost 50 percent. The likelihood of death among lymphoma
      patients who underwent HSCT was almost 5 percentage points lower, a 70 percent
      reduction in the probability of death. CONCLUSIONS: The findings raise concern
      about access to expensive, but highly effective cancer treatments for patients
      with certain hematologic malignancies.

PMID- 25047948
TI  - David I reimplantation procedure for aortic root replacement in Marfan patients:
      medium-term outcome.
AB  - OBJECTIVES: Technical variations of the David reimplantation valve-sparing aortic
      root replacement (V-SARR) procedure have been proposed to be advantageous in
      patients with connective tissue disease, such as the Marfan syndrome (MFS). We
      report results of a Marfan cohort treated exclusively with the non-modified David
      I procedure. METHODS: Forty-eight Marfan patients (25 males, mean age 33 +/- 12
      years, range 15-62 years) underwent the original variant of the David V-SARR
      (David I) between 1997 and 2013. Forty-two operations (88%) were performed as
      elective procedures for aortic root aneurysms and six for acute dissections
      (12%). Seventeen had aortic regurgitation (AR) grades >=2+ preoperatively, and 3
      had AR >2+. No patients with severe AR (4+) were selected for V-SARR. Three full
      or hemi-arch replacements were performed. Patients who were operated on using a
      variation of the David I or David II procedure were excluded. RESULTS: Mean
      prosthesis size was 28 +/- 3 mm (18-30 mm). Mean clinical and echocardiographic
      follow-up (98% complete) was 3.8 +/- 3.7 years with a cumulative follow-up of 178
      patient-years. The early mortality rate was 2% (one hospital death). The survival
      rate was 98% (95% confidence 84-99%) at 4 years and 90% (57-98%) at 8 years with
      5 patients at risk at 10 years. The rate of freedom from root or valve
      reoperation was 97% (79-99%) and 97% (79-99%) at 4 and 8 years, respectively.
      Only one patient required mechanical aortic valve replacement for progression of
      AR. CONCLUSIONS: Despite potential theoretical drawbacks of the David I V-SARR
      technique without neo-sinuses or a neo-sinotubular junction, it results in a
      favourable mid-term outcome in Marfan patients and compares well with reported
      results of different modifications of David V-SARR.

PMID- 25047950
TI  - Family centered care and family nursing: three beliefs that matter most.

PMID- 25047949
TI  - Targeted enzyme prodrug therapy for metastatic prostate cancer - a comparative
      study of L-methioninase, purine nucleoside phosphorylase, and cytosine deaminase.
AB  - BACKGROUND: Enzyme prodrug therapy shows promise for the treatment of solid
      tumors, but current approaches lack effective/safe delivery strategies. To
      address this, we previously developed three enzyme-containing fusion proteins
      targeted via annexin V to phosphatidylserine exposed on the tumor vasculature and
      tumor cells, using the enzymes L-methioninase, purine nucleoside phosphorylase,
      or cytosine deaminase. In enzyme prodrug therapy, the fusion protein is allowed
      to bind to the tumor before a nontoxic drug precursor, a prodrug, is introduced.
      Upon interaction of the prodrug with the bound enzyme, an anticancer compound is
      formed, but only in the direct vicinity of the tumor, thereby mitigating the risk
      of side effects while creating high intratumoral drug concentrations. The
      applicability of these enzyme prodrug systems to treating prostate cancer has
      remained unexplored. Additionally, target availability may increase with the
      addition of low dose docetaxel treatment to the enzyme prodrug treatment, but
      this effect has not been previously investigated. To this end, we examined the
      binding strength and the cytotoxic efficacy (with and without docetaxel
      treatment) of these enzyme prodrug systems on the human prostate cancer cell line
      PC-3. RESULTS: All three fusion proteins exhibited strong binding; dissociation
      constants were 0.572 nM for L-methioninase-annexin V (MT-AV), 0.406 nM for purine
      nucleoside phosphorylase-annexin V (PNP-AV), and 0.061 nM for cytosine deaminase
      annexin V (CD-AV). MT-AV produced up to 99% cell death (p < 0.001) with limited
      cytotoxicity of the prodrug alone. PNP-AV with docetaxel created up to 78% cell
      death (p < 0.001) with no cytotoxicity of the prodrug alone. CD-AV with docetaxel
      displayed up to 60% cell death (p < 0.001) with no cytotoxicity of the prodrug
      alone. Docetaxel treatment created significant increases in cytotoxicity for PNP
      AV and CD-AV. CONCLUSIONS: Strong binding of fusion proteins to the prostate
      cancer cells and effective cell killing suggest that the enzyme prodrug systems
      with MT-AV and PNP-AV may be effective treatment options. Additionally, low-dose
      docetaxel treatment was found to increase the cytotoxic effect of the annexin V
      targeted therapeutics for the PNP-AV and CD-AV systems.

PMID- 25047951
TI  - [Young first-time parents' experiences with family-centred postpartal health care
      in Switzerland].
AB  - BACKGROUND: Routine postnatal care normally addresses only the mother and her
      child. In Switzerland, counselling for all parents and their children is provided
      by family nurses in a community-based health care setting. We implemented a new
      approach to ensure father involvement within the framework of the Calgary Family
      Assessment (CFAM) and the Calgary Intervention Model CFIM of Wright and Leahey
      (2013) in the northwest of Switzerland. AIM: This qualitative study explored how
      mothers and fathers experienced the newly developed family-centred consultation.
      METHOD: Data collection was performed by means of participant observation and
      semi- structured interviews with a sample of five first-time parents with healthy
      neonates. Data were analysed by using content analysis according to Mayring.
      RESULTS: Mothers and fathers experienced family-centred consultation as
      effective. They felt more secure and confident "to handle the new situation" and
      obtained trustful, concrete and professional support to take care of their baby,
      particularly with regard to breast feeding, crying and sleeping patterns.
      CONCLUSIONS: Fathers felt included into postnatal care from the beginning. Family
      nursing offers a useful framework for family-centred postnatal health care.

PMID- 25047952
TI  - [Development of a nurse-led family counseling program for families of the
      elderly: the first cycle of a Community-Based Action Research Project (CBPR)].
AB  - BACKGROUND: With the support of family members many elderly people can live an
      independent life at home. Accepting support respectively providing support might
      be a challenge for both elder and family member. Families often have little
      professional support to manage those challenges. AIM: Therefore, a nurse-led
      counseling program for families of the elders has been established. METHOD: The
      counseling program was developed with community-based participatory research
      (CBPR) methodology using individual and focus group interviews, as well as a
      written survey and tested in a pilot study. RESULTS: Managing disease in everyday
      life, helpful means of support at home, changes in family relations, information
      about services as well as information how to navigate the healthcare system have
      been themes to discuss in the counseling sessions. Participants in the pilot
      study showed a statistically not significant increase in well-being, and
      preparedness for care and were highly satisfied with the counseling program.
      CONCLUSIONS: Families of the elderly could actively participate in developing and
      researching a nurse-led family counseling program. Several family members still
      engage as co-researcher in the program and participate to improve the new
      service.

PMID- 25047953
TI  - [The role of family carers of people with dementia in the assessment of need on
      the example of the CarenapD study].
AB  - Need driven dementia care at home requires the use of needs assessments like
      CarenapD. The CarenapD Manual states that the person with dementia (PwD) and
      caregivers (CA) should be included in the assessment process. In a pre-post study
      CarenapD has been applied in PwD (n = 55) and CA (n = 49) by professional staff
      (n = 15), CA were much more involved than PwD. Needs in PwD in T0 and T1 showed
      frequently functional needs(50 %), no need were frequently found in dementia
      specific needs (42 %) and frequently unmet need was present in social needs (35
      %). Burden-related needs in CA were reduced from T0 to T1 in daily difficulties (
      14 %), support (-20 %) and breaks from caring (-9 %).This secondary analysis
      compares the need results of PwD and CA to discuss the unequal involvement of
      clients. In this secondary analysis needs data of PwD and CA is included. Need in
      PwD at T0 and T1 showed frequently met functional need (50 %), frequently no need
      in dementia specific needs (42 %) and high unmet need in social needs (35 %).
      Burden in CA could be reduced from T0 to T1 in Daily Difficulties (-14 %),
      Support (-20 %) and Breaks from Caring (9 %). Compared to the literature it is
      remarkable that a high rate in no need was found in dementia specific needs.
      Needs of CA show congruent results, it seems to have come to relief of burden in
      CA. Lack of knowledge and shame in CA as well as the continuous presence of both
      clients within the assessment process may have caused that dementia-specific
      needs were not enough addressed. PwD and CA should be actively involved in the
      assessment process and should contribute their individual point of view, as
      stated in the CarenapD Manual. 

PMID- 25047954
TI  - [Men as caregivers for their wives - two phenomenological studies of the
      experiences of male primary caregivers in home arrangements. Part 1: men as
      caregivers for their wives after stroke].
AB  - BACKGROUND: In Germany, men participate more and more in the extensive process of
      caring for their relatives. The ongoing discourse in nursing sciences, however,
      reflects poorly on this increasing number of male principal caregivers. AIM:
      Objective of the present study is to analyse the following questions, with focus
      on caring husbands: Firstly, how do caring husbands experience caring for their
      wives after stroke? And secondly, how do they organise daily life? METHOD:
      Narrative interviews with ten caring husbands were conducted. Analysis was
      performed using a modified phenomenological-interpretative approach as described
      by Diekelmann (1992). RESULTS: Six central issues evolved: "I never thought
      something like that'd happen to us ..." (disease as acute crisis); "I see her
      just the way she was when we first met ..." (relationship); "... since then I got
      her in home care." (care); "... this work, it's never been easy" (work and
      burden); "This new situation, well, you've got to adapt ..." (adaptation); "...
      because I do need some time for myself!" (support and relief). "Being
      responsible" emerged as a constitutive pattern, according to which caring
      husbands perceive their own life situation. CONCLUSION: Professional nurses
      should take this constitutive pattern seriously and should align their work to it
      when collaborating with male principal care givers. For this purpose, further
      research is needed to develop new approaches to this special situation and its
      implications.

PMID- 25047955
TI  - [Family Health Nursing - a challenge for education and training? Results of an
      European project].
AB  - BACKGROUND: Since the WHO study "Family Health Nursing" (FHN) the concepts have
      been established different within Europe. Due to this, the international project
      "Family Health Nursing in European Communities" was started in order to develop a
      standardised educational concept. AIMS: The aim of this project was to gather the
      different requirements and to clarify problematic issues within the participating
      EU countries. METHOD: Thus, a literature review, a Delphi study in order to
      achieve consensus on definition of FHN, an analysis of competencies and
      requirements as well as an overview of available education/training with experts
      from the field of care was carried out. RESULTS: The results of the review
      reflect the varying level of occupation within the countries included in this
      analysis. Over the time, various conceptual orientations and professional
      designations have been established. Within this project the preferred job title
      was "Family Nurse" (46,3 %). Health promotion and prevention (85,8 %) were seen
      as main tasks of the Family Health Nurse. Therefore, the respondent experts state
      the need for more specialized training at an undergraduate (81,5 %) level.
      CONCLUSIONS: The project outlines the countries' effort towards a high-level in
      familial care which could be supported in long term by a consistent FHN concept.

PMID- 25047957
TI  - AtfA, a new factor in global regulation of transcription in Acinetobacter spp.
AB  - Acinetobacter species are widely distributed bacteria in the environment, and
      have recently gained notoriety as opportunistic nosocomial pathogens. Here we
      characterize a novel RNA polymerase-interacting protein named acidic
      transcription factor A, AtfA. It is small and highly acidic, and is widely
      distributed throughout the gamma proteobacteria, including other significant
      pathogens in the genera Moraxella, Pseudomonas, Legionella and Vibrio. In the
      model species A. baylyi ADP1, deletion of atfA significantly affects expression
      of over 500 genes, resulting in a large cell phenotype, reduced cell fitness,
      impaired biofilm formation and twitching motility, and increased sensitivity to
      antibiotics. Deletion of atfA also causes dramatically enhanced sensitivity to
      ethanol, which is an important growth promoter and virulence factor in
      Acinetobacter spp. The results suggest that auxiliary factors of RNA polymerase
      with important biological roles remain to be discovered. 

PMID- 25047956
TI  - Differential retention and expansion of the ancestral genes associated with the
      paleopolyploidies in modern rosid plants, as revealed by analysis of the
      extensins super-gene family.
AB  - BACKGROUND: All modern rosids originated from a common hexapolyploid ancestor,
      and the genomes of some rosids have undergone one or more cycles of
      paleopolyploidy. After the duplication of the ancient genome, wholesale gene loss
      and gene subfunctionalization has occurred. Using the extensin super-gene family
      as an example, we tracked the differential retention and expansion of ancestral
      extensin genes in four modern rosids, Arabidopsis, Populus, Vitis and Carica,
      using several analytical methods. RESULTS: The majority of extensin genes in each
      of the modern rosids were found to originate from different ancestral genes. In
      Arabidopsis and Populus, almost half of the extensins were paralogous duplicates
      within the genome of each species. By contrast, no paralogous extensins were
      detected in Vitis and Carica, which have only undergone the common gamma
      triplication event. It was noteworthy that a group of extensins containing the
      IPR006706 domain had actively duplicated in Arabidopsis, giving rise to a neo
      extensin around every 3 million years. However, such extensins were absent from,
      or rare in, the other three rosids. A detailed examination revealed that this
      group of extensins had proliferated significantly in the genomes of a number of
      species in the Brassicaceae. We propose that this group of extensins might play
      important roles in the biology and in the evolution of the Brassicaceae. Our
      analyses also revealed that nearly all of the paralogous and orthologous extensin
      pairs have been under strong purifying selection, leading to the strong
      conservation of the function of extensins duplicated from the same ancestral
      gene. CONCLUSIONS: Our analyses show that extensins originating from a common
      ancestor have been differentially retained and expanded among four modern rosids.
      Our findings suggest that, if Arabidopsis is used as the model plant, we can only
      learn a limited amount about the functions of a particular gene family. These
      results also provide an example of how it is essential to learn the origination
      of a gene when analyzing its function across different plant species.

PMID- 25047958
TI  - The synthetic biology toolbox for tuning gene expression in yeast.
AB  - Saccharomyces cerevisiae can serve as a key production platform for biofuels,
      nutraceuticals, industrial compounds, and therapeutic proteins. Over the recent
      years, synthetic biology tools and libraries have expanded in yeast to provide
      newfound control over regulation and synthetic circuits. This review provides an
      update on the status of the synthetic biology toolbox in yeast for use as a cell
      factory. Specifically, we discuss the impact of plasmid selection and
      composition, promoter, terminator, transcription factor, and aptamer selection.
      In doing so, we highlight documented interactions between these components,
      current states of development, and applications that demonstrate the utility of
      these parts with a particular focus on synthetic gene expression control.

PMID- 25047959
TI  - Development and retrospective validation of the juvenile spondyloarthritis
      disease activity index.
AB  - OBJECTIVE: To develop and validate the Juvenile Spondyloarthritis Disease
      Activity Index (JSpADA) for use in clinical practice and research. METHODS: Using
      modified Delphi consensus techniques, 10 items were selected by participants in
      the international pediatric rheumatology listserv, the Childhood Arthritis and
      Rheumatology Research Alliance, and the listserv for the pediatric section of the
      American College of Rheumatology. Validation was performed in a retrospective
      multicenter cohort of 244 children. RESULTS: In total, 106 physicians
      representing 14 countries completed the initial questionnaire. Completion rates
      for the subsequent questionnaires were 84%, 75%, and 77% of the original
      respondents. Ten items exceeded 80% consensus: arthritis, enthesitis, patient
      pain assessment, inflammatory markers, morning stiffness, clinical sacroiliitis,
      uveitis, back mobility, and patient and physician assessments of disease
      activity. After item analysis, 2 items were eliminated (patient and physician
      assessments of disease activity). Factor analysis identified 3 primary domains
      that explained 58% of the variance: peripheral disease, axial disease, and
      uveitis. The Cronbach's alpha coefficient was 0.66. The JSpADA had high or
      moderate correlations with the Juvenile Arthritis Disease Activity Score (r =
      0.81), patient and physician assessments of disease activity (r = 0.70 and r =
      0.66, respectively), and the Childhood Health Assessment Questionnaire (r =
      0.56). The JSpADA discriminated well between subjects with active versus inactive
      disease (P < 0.001) and was responsive to improvement or worsening in disease
      activity over time (P < 0.001). CONCLUSION: Using international input and
      consensus formation techniques, we developed and validated the first disease
      activity assessment for juvenile spondyloarthritis. Future studies should
      validate the JSpADA in a prospective multicenter cohort.

PMID- 25047960
TI  - Early sedation and clinical outcomes of mechanically ventilated patients: a
      prospective multicenter cohort study.
AB  - INTRODUCTION: Sedation overuse is frequent and possibly associated with poor
      outcomes in the intensive care unit (ICU) patients. However, the association of
      early oversedation with clinical outcomes has not been thoroughly evaluated. The
      aim of this study was to assess the association of early sedation strategies with
      outcomes of critically ill adult patients under mechanical ventilation (MV).
      METHODS: A secondary analysis of a multicenter prospective cohort conducted in 45
      Brazilian ICUs, including adult patients requiring ventilatory support and
      sedation in the first 48 hours of ICU admissions, was performed. Sedation depth
      was evaluated after 48 hours of MV. Multivariate analysis was used to identify
      variables associated with hospital mortality. RESULTS: A total of 322 patients
      were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%,
      respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration
      of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P =
      0.041) and more tracheostomies were performed in the deep sedation group (38.9%
      versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory
      distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio
      (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index
      >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3)
      score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to
      1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently
      associated with increased hospital mortality. CONCLUSIONS: Early deep sedation is
      associated with adverse outcomes and constitutes an independent predictor of
      hospital mortality in mechanically ventilated patients.

PMID- 25047962
TI  - Effects of constant and variable temperatures on development and reproduction of
      the two-spotted spider mite Tetranychus urticae (Acari: Tetranychidae).
AB  - We focused on the influence of different temperature amplitudes on development
      and reproduction of the two-spotted spider mite, Tetranychus urticae Koch, at a
      16:8 (L:D) h photoperiod and 60-95 % RH. The temperature amplitudes varied from 0
      to 24  degrees C in steps of 6  degrees C; i.e. 22 +/- 0, 22 +/- 3, 22 +/- 6, 22
      +/- 9 and 22 +/- 12  degrees C. Temperature changed every 24 h between a low and
      an upper value, but without changing the average temperature (22  degrees C). The
      number of eggs laid by five females for 24 h was slightly lower at 22 +/- 12 
      degrees C than at constant temperature (22 +/- 0  degrees C), and egg
      hatchability differed among the five temperature regimes. Developmental time at
      22 +/- 0  degrees C was shorter than that at 22 +/- 3 and 22 +/- 6  degrees C,
      but longer than that at 22 +/- 9 and 22 +/- 12  degrees C. The oviposition
      period, total fecundity per female and adult longevity gradually decreased with
      increasing amplitudes. Sex ratio was similar at all five temperature regimes. The
      intrinsic rate of natural increase (r m) was affected by temperature amplitude
      and the r m-values at all amplitudes except 22 +/- 12  degrees C were higher than
      that at constant temperature. Thus, this study showed that variable temperature
      regimes influence population growth rates of T. urticae and that large amplitude
      regimes are stressful for this species. 

PMID- 25047961
TI  - Prevalence of tick-borne encephalitis virus (TBEV) RNA in Dermacentor reticulatus
      ticks from natural and urban environment, Poland.
AB  - Tick-borne encephalitis virus (TBEV) (Flaviviridae, Flavivirus) is an arthropod
      borne virus, an etiologic agent of tick-borne encephalitis (TBE), a human
      infection involving the central nervous system. The disease is endemic in a large
      region in Eurasia, where it is transmitted mainly by Ixodes ricinus and Ixodes
      persulcatus ticks. It is known that also Dermacentor reticulatus is involved in
      circulation of TBEV. However, the current knowledge of D. reticulatus importance
      in TBE epidemiology is still insufficient. A total of 471 adult D. reticulatus
      ticks were collected by flagging vegetation in the Bialowieza Primeval Forest,
      Biebrza National Park, Masurian Landscape Park (North-Eastern Poland) and in the
      city of Warsaw in the years 2007-2010. All collected ticks were examined
      individually for the presence of RNA of TBEV using nested RT-PCR assay. Positive
      results were noted in all investigated localities with the infection rate ranging
      from 0.99 to 12.5 % with a total mean of 2.12 %. The difference in the percentage
      of infective males and females was not statistically significant. 

PMID- 25047963
TI  - [Not Available].

PMID- 25047966
TI  - Analysis of the population genetics of clades of enterohaemorrhagic Escherichia
      coli O157:H7/H- isolated in three areas in Japan.
AB  - AIMS: The genetic differences of enterohaemorrhagic Escherichia coli O157 (O157)
      strains isolated from humans in three widely-separated areas in Japan were
      analysed to provide information on possible geographic aspects of O157
      pathogenicity. METHODS AND RESULTS: Epidemiologically unlinked O157 strains were
      isolated in Chiba (300 strains), Fukuoka (260 strains) and Yamagata (81 strains)
      prefectures. These strains were classified in clades by single nucleotide
      polymorphism in seven loci and lineage-specific polymorphism assay-6, and
      differences between the strains in each clade were compared by population genetic
      analyses using the IS-printing system. Analysis of the clades from the three
      areas showed linkage disequilibrium of the strains in each clade. Comparison of
      the genetic differences of strains from the three areas in each clade, from
      calculated PhiPT values, indicated that the strains in each clade were the same
      population in all three areas, except possibly the clade 12 strains. CONCLUSIONS:
      Population genetics analyses confirmed that the distribution of O157 strains in
      the clades isolated in three areas in Japan were similar and stable. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The pathogenicity of O157 strains infecting humans was
      comparable due to the similar, stable geographic distribution of O157 clades.

PMID- 25047967
TI  - A fast deposition-crystallization procedure for highly efficient lead iodide
      perovskite thin-film solar cells.
AB  - Thin-film photovoltaics based on alkylammonium lead iodide perovskite light
      absorbers have recently emerged as a promising low-cost solar energy harvesting
      technology. To date, the perovskite layer in these efficient solar cells has
      generally been fabricated by either vapor deposition or a two-step sequential
      deposition process. We report that flat, uniform thin films of this material can
      be deposited by a one-step, solvent-induced, fast crystallization method
      involving spin-coating of a DMF solution of CH3NH3PbI3 followed immediately by
      exposure to chlorobenzene to induce crystallization. Analysis of the devices and
      films revealed that the perovskite films consist of large crystalline grains with
      sizes up to microns. Planar heterojunction solar cells constructed with these
      solution-processed thin films yielded an average power conversion efficiency of
      13.9+/-0.7% and a steady state efficiency of 13% under standard AM 1.5
      conditions.

PMID- 25047968
TI  - [A new strategy in the surgical treatment of multiple liver tumors - ALPPS].
AB  - INTRODUCTION: This systematic review was performed to introduce the two-staged
      hepatectomy procedure (Associating Liver Partition and Portal Vein Ligation for
      Staged Hepatectomy - ALPPS) and present its current results. MATERIAL AND
      METHODS: We conducted a systematic literature search using the PubMed database
      with key words "ALPPS" or "staged liver resection". The inclusion criteria were
      randomized trials or cohort studies. Case reports were excluded. The primary end
      point was the assessment of liver tissue hypertrophy after the ALPPS procedure.
      Morbidity and mortality evaluation were the secondary end-point. RESULTS: After
      an electronic data search of PubMed with the selected key words, six cohort
      studies evaluating 96 patients met the inclusion criteria. There was no
      prospective randomised trial. Based on the results of the individual studies,
      liver hypertrophy ranged from 74 to 87%. Morbidity and mortality ranged from 53
      to 71% and 0 to 13% respectively. CONCLUSIONS: Despite the higher morbidity and
      mortality the ALPPS procedure could be a promising technique for a selected group
      of patients with multiple liver tumors. However long term results are not yet
      available.

PMID- 25047969
TI  - [A study of the morphology of the descending branch of the lateral circumflex
      femoral artery (DBLCFA) as a possible vascular graft for the reconstruction of
      coronary arteries using angio CT].
AB  - INTRODUCTION: Due to the need for alternative arterial grafts suitable for the
      reconstruction of the coronary bloodstream, we conducted a morphological analysis
      of the descending branch of the lateral circumflex femoral artery (DBLCFA) using
      an AGCT scan. MATERIAL AND METHODS: Not only anatomical variations and the
      quantitative representation of sclerotic changes, but also the presence of a
      collateral system in the event of significant stenosis of the pelvic and femoral
      artery system were analysed. RESULTS: The results revealed favorable findings in
      the sense of the studied arteries length (9.3 cm on average), a relatively low
      anatomical variability and a very small percentage of the studied blood vessels
      participating in collateral blood flow, despite that 72% of tests revealed
      significant stenotic disease (stenosis of more than 50%) of the upper branch of
      lower limb arteries. CONCLUSION: According to the defined criteria, 68% of
      vessels were found to be suitable for grafting. We suppose that this number would
      be considerably higher in patients with only insignificant or no ischemic disease
      of the lower extremities.

PMID- 25047970
TI  - [Colon cancer - evaluation of complications and risks of planned resections].
AB  - INTRODUCTION: Resection procedures for colorectal cancer are burdened with a
      relatively high number of complications. The aim of this study is to define risk
      factors associated with the development of postoperative complications based on
      retrospective data analysis. MATERIAL AND METHODS: From January 1 st 2007 to
      December 31st 2012, 1093 patients underwent surgery for colorectal cancer.
      Retrospectively, we selected a group of 406 patients who underwent planned,
      elective colon resection for colon cancer. Open surgery was performed in 158
      patients (38.9%), laparoscopic resection in 248 patients (61.1%). Based on
      initial staging of the disease, there were 85 patients (20.9%) in stage I, 137
      patients (33.8%) in stage II, 110 patients (27.1%) in stage III and 74 patients
      (18.2%) in stage IV. Postoperative complications were evaluated according to
      Clavien - Dindo classification. RESULTS: Grade I complications were observed in
      34 patients (8.4%), grade II in 25 patients (6.2%), grade III in 43 patients
      (10.6%), grade IV in 7 patients (1.7%) and grade V in 8 patients (2.0%). The
      highest incidence of complications was observed in left colon resection
      procedures (41.1%), open resections (39.8%), procedures lasting longer than 301
      minutes (50%), patients older than 81 years (41.6%) and in procedures performed
      by the youngest, less experienced surgeon (40.6%). CONCLUSION: Our results
      confirmed that the type and approach of surgical procedure, patients age and
      surgeons experience are risk factors associated with a higher incidence of
      postoperative complications. High-risk surgical patients should be operated on by
      experienced surgeon who regularly performs a high number of resection procedures.

PMID- 25047971
TI  - [Comparison between femoropopliteal bypass and subintimal recanalization in the
      treatment of critical limb ischaemia].
AB  - INTRODUCTION: Revascularization of occlusion of the femoropopliteal region in
      patients with critical limb ischaemia (CLI) may be performed following the
      standard surgical approach using bypass with the saphenous vein graft (FP
      bypass). Unfortunately, up to 40% of these patients do not have a suitable
      saphenous vein. In these patients, revascularization may be performed surgically
      using bypass with prosthesis, allograft vein or by interventional radiological
      methods. An endovascular alternative is represented by subintimal recanalization
      (SIR). MATERIAL AND METHODS: Our prospective analysis evaluated mid-term results
      of revascularization using FP bypass or SIR in patients with occlusion of the
      femoropopliteal region and CLI. Our aim was to answer the question whether SIR
      can fully replace FP bypass in certain indications. From January 2010 to December
      2012, 59 revascularizations of the CLI (Rutherford 5-6) with comparable SFA
      occlusion were performed. We monitored the immediate postoperative course,
      technical and clinical success and the process of healing of the defect. RESULTS:
      Healing of the defect was achieved in 78.6% of patients with FP bypass using the
      saphenous vein, in 62.5% of patients with FP bypass using prosthesis and in 64.9%
      of patients with SIR (P=0.578). When comparing the bypass group, which was
      subdivided into a group with revascularization using autologous vein and a group
      with revascularization using ePTFE prosthesis, with the SIR group, primary
      patency was evaluated. The results for vein 78.0% after 6, 12, 24 and 36 months,
      for prosthesis 74.5%, 55%, 55% after 6, 12 and 24 months, and for the SIR group
      78%, 60%, 51.3% and 50.7% after 6,12,24 and 36 months. When comparing the results
      of the groups, no statistically significant difference was found (P =0.625).
      CONCLUSION: As expected, the most successful method of choice is
      revascularization by FPB using the saphenous vein. SIR and FP bypass using
      prosthesis had similar results with respect to healing of the defects.

PMID- 25047972
TI  - [Primary small bowel volvulus in a young adult].
AB  - The authors present a rare case of a young male patient with primary small bowel
      volvulus. They show the main points to be considered in clinical diagnosis of
      this kind of acute abdomen and the importance of CT scan in such cases.

PMID- 25047973
TI  - [Complex surgical management of hemodialysis vascular access infection caused by
      Clostridium perfringens].
AB  - Infection of prosthetic hemodialysis (HD) shunts is one of the most common
      complications of vascular access in hemodialysis patients. The incidence of
      anaerobic infection is very rare. In such a case, management of treatment
      represents a great challenge for the surgeon. We report a complicated case of
      autologous hemodialysis shunt infected by Clostridium perfringens on the right
      forearm in a polymorbid female patient with chronic renal failure and
      myelodysplastic syndrome. The patient has undergone repeated establishment of HD
      shunt with subsequent polybacterial local infectious complications. Destructive
      clostridial infection developed at the site of the infectious complications. This
      very rare complication involving infection by an atypical bacterial agent
      requires rapid diagnosis and comprehensive multimodal treatment including
      surgical, antibiotic and supportive therapy. Clinical implications and optimal
      therapy is not precisely defined in these cases.

PMID- 25047974
TI  - [Clostridial myonecrosis of the abdominal wall - case report].
AB  - The authors present a case report of a forty-five-year-old patient operated on
      for acute appendicitis who developed gas gangrene of the abdominal wall within 48
      hours after an appendectomy and subsequently also clostridial sepsis. Due to
      early diagnosis and intensive care, the patient survived. Clostridial myonecrosis
      is a rare complication after abdominal surgery and may be fatal in many cases. In
      our literature, there are only a few publications describing cases of patients
      who survived this rare postoperative complication.

PMID- 25047975
TI  - [Basic principles of diagnosis and treatment of secondary peritonitis -
      recommendations of experts with the support of SIS].
AB  - Secondary peritonitis is the most common cause of inflammatory acute abdomen
      treated at general surgery departments. Only early and correct diagnosis may
      improve the prognosis of these patients. The authors compiled an
      interdisciplinary review of the basic principles of diagnosis and treatment of
      secondary peritonitis, which reflects current findings supported by evidence
      based medicine. The work is based on published international literature but also
      shares opinions and experiences of the selected specialists. The presented work
      in its extent is not meant to substitute an in-depth study of the issue, but to
      allow a basic and quick review of the topic.

PMID- 25047976
TI  - Genome sequence of Kosakonia radicincitans UMEnt01/12, a bacterium associated
      with bacterial wilt diseased banana plant.
AB  - Kosakonia radicincitans (formerly known as Enterobacter radicincitans), an
      endophytic bacterium was isolated from the symptomatic tissues of bacterial wilt
      diseased banana (Musa spp.) plant in Malaysia. The total genome size of K.
      radicincitans UMEnt01/12 is 5 783 769 bp with 5463 coding sequences (CDS), 75
      tRNAs, and 9 rRNAs. The annotated draft genome of the K. radicincitans UMEnt01/12
      strain might shed light on its role as a bacterial wilt-associated bacterium.

PMID- 25047977
TI  - ATX1/AtCOMPASS and the H3K4me3 marks: how do they activate Arabidopsis genes?
AB  - Despite the proven correlation between gene transcriptional activity and the
      levels of tri-methyl marks on histone 3 lysine4 (H3K4me3) of their nucleosomes,
      whether H3K4me3 contributes to, or 'registers', activated transcription is still
      controversial. Other questions of broad relevance are whether histone-modifying
      proteins are involved in the recruitment of Pol II and the general transcription
      machinery and whether they have roles other than their enzyme activities. We
      address these questions as well as the roles of the ARABIDOPSIS HOMOLOG OF
      TRITHORAX1 (ATX1), of the COMPASS-related (AtCOMPASS) protein complex, and of
      their product, H3K4me3, at ATX1-dependent genes. We suggest that the ambiguity
      about the role of H3K4me3 as an activating mark is due to the unknown duality of
      the ATX1/AtCOMPASS to facilitate PIC assembly and to generate H3K4me3, which is
      essential for activating transcriptional elongation. 

PMID- 25047978
TI  - Age influences initial dose and compliance to imatinib in chronic myeloid
      leukemia elderly patients but concomitant comorbidities appear to influence
      overall and event-free survival.
AB  - We applied Charlson comorbidity index (CCI) stratification on a large cohort of
      chronic myeloid leukemia (CML) very elderly patients (>75 years) treated with
      imatinib, in order to observe the impact of concomitant diseases on both
      compliance and outcome. One hundred and eighty-one patients were recruited by 21
      Italian centers. There were 95 males and 86 females, median age 78.6 years (range
      75-93.6). According to Sokal score, 106 patients were classified as intermediate
      risk and 55 as high risk (not available in 20 patients). According to CCI
      stratification, 71 patients had score 0 and 110 a score >= 1. Imatinib standard
      dose was reduced at start of therapy (200-300 mg/day) in 68 patients
      independently from the evaluation of baseline comorbidities, but based only on
      physician judgement: 43.6% of these patients had score 0 compared to 34% of
      patients who had score >= 1. Significant differences were found in terms of
      subsequent dose reduction (39% of patients with score 0 compared to 53% of
      patients with score >= 1) and in terms of drug discontinuation due to toxicity
      (35% of patients with score 0 vs 65% of patients with score >= 1). We did not
      find significant differences as regards occurrence of hematologic side effects,
      probably as a consequence of the initial dose reduction: 39% of patients with
      score 0 experienced grade 3/4 hematologic toxicity (most commonly anemia)
      compared to 42% of patients with score >= 1. Independently from the initial dose,
      comorbidities again did not have an impact on development of grade 3/4 non
      hematologic side effects (most commonly skin rash, muscle cramps and fluid
      retention): 62% of patients with score 0 compared to 52.5% of patients with score
      >= 1. Notwithstanding the reduced dose and the weight of comorbidities we did not
      find significant differences but only a trend in terms of efficacy: 66% of
      patients with score 0 achieved a CCyR compared to 54% of patients with score >=
      1. Comorbidities appeared to have an impact on median OS (40.8 months for
      patients with score 0 vs 20.16 months for patients with score >= 1) on EFS and on
      non-CML death rate. Our results suggest that treatment of very elderly CML
      patients might be influenced by personal physician perception: evaluation at
      baseline of comorbidities according to CCI should improve initial decision-making
      in this subset of patients.

PMID- 25047979
TI  - Phase II study of pomalidomide in combination with prednisone in patients with
      myelofibrosis and significant anemia.
AB  - We evaluated pomalidomide with prednisone for myelofibrosis (MF) with significant
      anemia (hemoglobin < 10 g/dL). Patients (n = 29; 18 RBC-transfusion dependent)
      received 0.5mg pomalidomide daily in continuous 28-day cycles with prednisone
      given for the first 3 cycles only. Six (21%) patients responded (median response
      duration 11.4 months), including four who achieved RBC-transfusion-independence
      per the Delphi criteria and two who achieved clinical improvement (in platelets
      and spleen, respectively) per the International Working Group for Myelofibrosis
      Research and Treatment criteria. Grade 3 toxicity occurred in 1 patient
      (fatigue). Pomalidomide with prednisone is safe therapy with modest activity in
      patients with MF and anemia. ClinicalTrials.gov Identifier: NCT00946270.

PMID- 25047980
TI  - Who gets fired, who gets re-hired: the role of workers' contract, age, health,
      work ability, performance, work satisfaction and employee investments.
AB  - PURPOSE: Many workers have been dismissed in the past few years, either becoming
      unemployed or finding re-employment. The current study examined whether dismissal
      and its follow-up for the employee (re-employment versus unemployment) could be
      predicted from workers' employment contract and age, and their health status,
      work ability, work performance, work satisfaction and employee investments at
      baseline. METHODS: Our sample comprised a selection of participants from the
      Netherlands Working Conditions Survey 2010 who participated in a follow-up
      questionnaire in 2012 (N = 2,644). We used logistic regression analyses to test
      our hypotheses. RESULTS: Temporary employment, low health status, low work
      ability, poor work performance, low work satisfaction and no employee investments
      in terms of training predicted future dismissal. Furthermore, older workers and
      workers reporting decreased work performance due to impaired health at baseline
      had a lower chance of re-employment after being dismissed. Interestingly, after
      taking into account all predictors, former temporary workers without permanent
      employment prospects had much better chances of re-employment after their
      dismissal than former permanent workers. CONCLUSIONS: Temporary, less healthy,
      low work ability, poor performing, dissatisfied and "under-invested" workers are
      at risk for dismissal, whereas older and less healthy workers are (also) at risk
      for long-term unemployment after being dismissed.

PMID- 25047981
TI  - Risk of ischemic heart disease following occupational exposure to welding fumes:
      a systematic review with meta-analysis.
AB  - PURPOSE: Air pollution has been linked to an increased risk of ischemic heart
      disease (IHD), but less is known about occupational exposure to welding fumes and
      the risk of IHD. The objective of this paper was to review the epidemiological
      evidence on causal links between welding fume exposure and risk of IHD and to
      investigate whether the risk of IHD depends on specific welding characteristics.
      METHODS: A systematic search in Medline 1979-2013 and EMBASE 1974-2013 identified
      18 epidemiological studies with at least one risk estimate of IHD morbidity or
      mortality among workers exposed to welding fumes. Following an assessment of
      completeness of reporting, confounding, and bias, each risk estimate was
      characterized as more or less reliable. Pooled risk estimates were computed
      across studies by random effect meta-analyses. RESULTS: The weighted relative
      risk (RR) for IHD following exposure to welding fumes was 1.09 [95 % confidence
      interval (CI) 1.00, 1.19]. We calculated a RR of 1.39 (95 % CI 0.96, 2.02) among
      studies using an internal reference group and 1.08 (95 % CI 0.99, 1.18) for
      studies using an external reference group. An increased risk was observed for
      acute myocardial infarction RR = 1.69 (95 % CI 1.18, 2.42) and other IHDs RR =
      1.06 (95 % CI 0.98, 1.14). There was too limited evidence to evaluate the risk of
      IHD related to specific welding characteristics. CONCLUSION: Several studies
      indicate that welding is associated with a moderately increased risk of IHD;
      however, bias and confounding cannot be ruled out with reasonable confidence.

PMID- 25047984
TI  - Prescribing marijuana? You have more than 200 options.

PMID- 25047983
TI  - Predictors of early and late stroke following cardiac surgery.
AB  - BACKGROUND: Much is known about the short-term risks of stroke following cardiac
      surgery. We examined the rate and predictors of long-term stroke in a cohort of
      patients who underwent cardiac surgery. METHODS: We obtained linked data for
      patients who underwent cardiac surgery in the province of Ontario between 1996
      and 2006. We analyzed the incidence of stroke and death up to 2 years
      postoperatively. RESULTS: Of 108,711 patients, 1.8% (95% confidence interval [CI]
      1.7%-1.9%) had a stroke perioperatively, and 3.6% (95% CI 3.5%-3.7%) had a stroke
      within the ensuing 2 years. The strongest predictors of both early and late
      stroke were advanced age (>= 65 year; adjusted hazard ratio [HR] for all stroke
      1.9, 95% CI 1.8-2.0), a history of stroke or transient ischemic attack (adjusted
      HR 2.1, 95% CI 1.9-2.3), peripheral vascular disease (adjusted HR 1.6, 95% CI 1.5
      1.7), combined coronary bypass grafting and valve surgery (adjusted HR 1.7, 95%
      CI 1.5-1.8) and valve surgery alone (adjusted HR 1.4, 95% CI 1.2-1.5).
      Preoperative need for dialysis (adjusted odds ratio [OR] 2.1, 95% CI 1.6-2.8) and
      new-onset postoperative atrial fibrillation (adjusted OR 1.5, 95% CI 1.3-1.6)
      were predictors of only early stroke. A CHADS2 score of 2 or higher was
      associated with an increased risk of stroke or death compared with a score of 0
      or 1 (19.9% v. 9.3% among patients with a history of atrial fibrillation, 16.8%
      v. 7.8% among those with new-onset postoperative atrial fibrillation and 14.8% v.
      5.8% among those without this condition). INTERPRETATION: Patients who had
      cardiac surgery were at highest risk of stroke in the early postoperative period
      and had continued risk over the ensuing 2 years, with similar risk factors over
      these periods. New-onset postoperative atrial fibrillation was a predictor of
      only early stroke. The CHADS2 score predicted stroke risk among patients with and
      without atrial fibrillation.

PMID- 25047985
TI  - MediData: how many types of medical marijuana are for sale?

PMID- 25047986
TI  - Collaborative practice among obstetricians, family physicians and midwives.

PMID- 25047987
TI  - Tranexamic acid for trauma-related hemorrhage.

PMID- 25047990
TI  - Ethicists resign to protest CIHR stance.

PMID- 25047989
TI  - Rehabilitation for patients with advanced cancer.

PMID- 25047991
TI  - BMA votes to end investment in fossil fuels.

PMID- 25047993
TI  - The Proceedings of Medical Quality 2014.

PMID- 25047992
TI  - Assessment of diabetes acceptance can help identify patients with ineffective
      diabetes self-care and poor diabetes control.
AB  - AIMS: To estimate the associations between insufficient diabetes acceptance and
      relevant diabetes outcomes. METHODS: A total of 320 patients completed
      questionnaires on diabetes non-acceptance (the Acceptance and Action Diabetes
      Questionnaire), diabetes distress (the Problem Areas in Diabetes Scale),
      depressive mood (the Center for Epidemiologic Studies Depression Scale), coping
      with illness (the Freiburg Questionnaire of Coping with Illness), self-care
      activities (the Summary of Diabetes Self-Care Activities Measure) and quality of
      life (the Short Form-36 Health Questionnaire). A six-item version of the
      Acceptance and Action Diabetes Questionnaire showing good reliability and
      validity was established, and the associations between insufficient acceptance
      and clinical outcomes were estimated. RESULTS: Higher diabetes non-acceptance
      correlated significantly with less active coping (-0.37), reduced self-care (
      0.43) and higher HbA1c levels (0.31), higher diabetes distress (0.53) and more
      depressive symptoms (0.36). Correlations of diabetes non-acceptance with diabetes
      self-care/glycaemic control were significantly higher than were those of
      depressive mood or diabetes distress with these criteria. CONCLUSIONS: Low
      diabetes acceptance is associated with impaired self-care and glycaemic control.
      Assessment of diabetes acceptance may facilitate the detection of patients at
      high risk and may present an essential target for treatments to improve diabetes
      control that is more relevant than elevated depressive mood or diabetes distress.

PMID- 25047994
TI  - Epidemiology of sudden cardiac death in Cameroon: rationale and design of the
      Douala-SUD survey.
AB  - BACKGROUND: The burden of sudden unexplained death in sub-Saharan Africa is
      unknown. AIM: The aim of this study is to establish the epidemiology of sudden
      cardiac death in Cameroon. METHODS: The Douala sudden unexplained death (Douala
      SUD) study is a prospective, multiple-source, community-based surveillance of all
      cases of unexpected death (< 24 hours from onset of symptoms) occurring in
      victims aged>15 years. After approval from institutional boards, all deaths
      occurring in residents of four areas of Douala city will be checked for
      circumstances of death and past medical history. Subjects who die naturally will
      be further investigated. Unexpected death victims will be checked for detailed
      demographic, clinical, electrocardiographic, echocardiographic and biological
      records. Autopsy background and genetic analysis (postmortem or in first
      relatives if the young victim is aged<40 years) will be performed as far as
      possible. Finally, the use of cardiopulmonary resuscitation efforts during the
      timeframe of sudden cardiac arrest will also be evaluated. CONCLUSION: The Douala
      SUD study will provide comprehensive, contemporary data on the epidemiology of
      sudden unexplained and cardiac death in sub-Saharan Africa and will help in the
      development of strategies to prevent and manage cardiac arrest in Cameroon as
      well as in other sub-Saharan countries.

PMID- 25047995
TI  - The investigation of the role of proteoglycans and ADAMTS levels in fetal
      membranes in physiopathological process of gestational diabetes.
AB  - About 2-5% of all pregnant women develop gestational diabetes mellitus (GDM)
      during pregnancy and its prevalence has increased markedly within the last
      decade. GDM is a metabolic syndrome produced by various degrees of carbohydrate
      intolerance during pregnancy. Various risk factors such as obesity, genetics,
      environmental factors, and hypertension have been described previously. Maternal
      and fetal complications occur in around 7% of pregnant women with GDM. In these
      patients, a relation between proteoglycans and ADAMTS proteases located in
      extracellular matrix in fetal membranes (placenta, cord, amnion) and complicated
      pregnancies has already been determined by various animal experiments. Changes in
      expression, structure and function of ADAMTS proteases and proteoglycans in fetal
      membranes lead to alteration in the structure of extracellular matrix. If we can
      establish a balance between these proteoglycans and ADMTS proteases or determine
      the changes in their structure and functions, it will be possible to predict the
      risk in high risk pregnancies at early weeks and to initiate treatment early or
      to follow the target population regularly. In addition, prevention or reduction
      of maternal and fetal complications may be possible. For this purpose, ADAMTS and
      proteoglycans the synthesis of which is too much or less, may be targeted and if
      we would be able to determine and prevent the changes in their levels in the
      early period of pregnancy, the development of GDM and its complications may be
      prevented or decreased. Thus, we may identify a marker for early diagnosis and
      treatment and reduce prematurity, which is the most common cause of fetal death.
      Fetal and maternal complications, and especially treatment and care costs of
      prematurity, may also be decreased.

PMID- 25047997
TI  - Total synthesis of (-)-platensimycin by advancing oxocarbenium- and iminium
      mediated catalytic methods.
AB  - (-)-Platensimycin is a potent inhibitor of fatty acid synthase that holds promise
      in the treatment of metabolic disorders (e.g., diabetes and "fatty liver") and
      pathogenic infections (e.g., those caused by drug-resistant bacteria). Herein, we
      describe its total synthesis through a four-step preparation of the aromatic
      amine fragment and an improved stereocontrolled assembly of the ketolide
      fragment, (-)-platensic acid. Key synthetic advances include 1) a modified Lieben
      haloform reaction to directly convert an aryl methyl ketone into its methyl ester
      within 30 seconds, 2) an experimentally improved dialkylation protocol to form
      platensic acid, 3) a sterically controlled chemo- and diastereoselective
      organocatalytic conjugate reduction of a spiro-cyclized cyclohexadienone by using
      the trifluoroacetic acid salt of alpha-amino di-tert-butyl malonate, 4) a
      tetrabutylammonium fluoride promoted spiro-alkylative para dearomatization of a
      free phenol to assemble the cagelike ketolide core with the moderate leaving
      group ability of an early tosylate intermediate, and 5) a bismuth(III)-catalyzed
      Friedel-Crafts cyclization of a free lactol, with LiClO4 as an additive to
      liberate a more active oxocarbenium perchlorate species and suppress the Lewis
      basicity of the sulfonyloxy group. The longest linear sequence is 21 steps with
      an overall yield of 3.8 % from commercially available eugenol. 

PMID- 25047996
TI  - Hyperplasticity in Autism Spectrum Disorder confers protection from Alzheimer's
      disease.
AB  - Autism Spectrum Disorders (ASD) currently affects approximately 1% of the
      population causing grave disability and necessitating a better understanding of
      the currently enigmatic etiology of these disorders. Recent data suggest that
      some patients with ASD may have a dysfunction in brain plasticity (specifically
      data from animal models and human studies suggest a propensity toward excessive
      amount of plasticity). Plasticity is essential to the establishment and
      maintenance of brain circuitry; however, too much plasticity may lead to
      instability of structural connections and compromise of functional systems
      necessary for cognition and behavior. Multiple lines of evidence suggest that
      plasticity declines throughout the age-span and may underlie age-related
      cognitive decline. We hypothesize that individuals whose cortex begins as
      relatively "hyperplastic" (such as may be seen in ASD) should then be relatively
      protected from age-related cognitive decline (which we suggest is related to a
      reduction in plasticity). In the current study, we conducted a multiple linear
      regression using age and diagnosis as predictor variables in order to evaluate
      strength of the relationship between age, diagnosis or an interaction of the two
      factors and the degree of modulation in cortical excitability by transcranial
      magnetic stimulation as an index of cortical plasticity. Results indicate that
      across the age-span individuals with ASD show a consistently increased modulation
      of cortical excitability as compared to typically developing individuals, such
      that the general slope of decline across the age span is matched across both
      groups. We have argued that an individual's risk of age-related cognitive decline
      (and risk for manifesting symptoms of dementia) depends on the individual's
      starting point and slopes of change in plasticity efficiency over the lifespan.
      Therefore, our results suggest that individuals with ASD might be relatively
      protected from age-related cognitive decline and the risk of dementia. 

PMID- 25047998
TI  - Modeling chronic brain exposure to amphetamines using primary rat neuronal
      cortical cultures.
AB  - Amphetamine-type psychostimulants (ATS) are used worldwide by millions of
      patients for several psychiatric disorders. Amphetamine (AMPH) and "ecstasy" (3,4
      methylenedioxymethamphetamine or MDMA) are common drugs of abuse. The impact of
      chronic ATS exposure to neurons and brain aging is still undisclosed. Current
      neuronal culture paradigms are designed to access acute ATS toxicity. We report
      for the first time a model of chronic exposure to AMPH and MDMA using long-term
      rat cortical cultures. In two paradigms, ATS were applied to neurons at day 1 in
      vitro (DIV) (0, 1, 10 and 100 MUM of each drug) up to 28 days (200 MUM was
      applied to cultures up to 14 DIV). Our reincubation protocol assured no decrease
      in the neuronal media's drug concentration. Chronic exposure of neurons to
      concentrations equal to or above 100 MUM of ATS up to 28 DIV promoted significant
      mitochondrial dysfunction and elicited neuronal death, which was not prevented by
      glutamate receptor antagonists at 14 DIV. ATS failed to promote accelerated
      senescence as no increase in beta-galactosidase activity at 21 DIV was found. In
      younger cultures (4 or 8 DIV), AMPH promoted mitochondrial dysfunction and
      neuronal death earlier than MDMA. Overall, AMPH proved more toxic and was the
      only drug that decreased intraneuronal glutathione levels. Meanwhile, caspase 3
      activity increased for either drug at 200 MUM in younger cultures at 8 DIV, but
      not at 14 DIV. At 8 DIV, ATS promoted a significant change in the percentage of
      neurons and astroglia present in culture, promoting a global decrease in the
      number of both cells. Importantly, concentrations equal to or below 10 MUM of
      either drug did not promote neuronal death or oxidative stress. Our paradigm of
      neuronal cultures long-term exposure to low micromolar concentrations of ATS
      closely reproduces the in vivo scenario, being valuable to study the chronic
      impact of ATS.

PMID- 25047999
TI  - Long-term effects of chronic cocaine exposure throughout adolescence on anxiety
      and stress responsivity in a Wistar rat model.
AB  - Adolescents display increased vulnerability to engage in drug experimentation.
      This is often considered a risk factor for later drug abuse. In this scenario,
      the permanent effects of cocaine exposure during adolescence on anxiety levels
      and stress responsivity, which may result in behavioral phenotypes prone to
      addiction, are now starting to be unveiled. Thus, the purpose of the present
      study was to evaluate the long-lasting effects of chronic cocaine administration
      during adolescence, on anxiety-like behavior and on stress response. Adolescent
      male Wistar rats were daily administered 45-mg cocaine/kg of body weight in three
      equal intraperitoneal doses with 1-h interval, from postnatal day (PND) 35 to 50.
      The effects of cocaine administration on anxiety levels, assessed in the Elevated
      Plus Maze (EPM), and on social stress response, assessed in the resident-intruder
      paradigm (R/I), were evaluated 10 days after withdrawal, when rats were reaching
      the adulthood. The underlying dopaminergic activity, and the corticosterone and
      testosterone levels were determined. Our results showed that cocaine induced long
      lasting alterations in the hypothalamus-pituitary-adrenals (HPA) axis function
      and in testosterone levels. Such alterations resulted in significant and enduring
      changes in behavioral responses to environmental challenges, such as the EPM and
      R/I, including the evaluation of potential threats that may lead to high-risk
      behavior and low-benefit choices. This was further supported by an altered
      dopaminergic function in the amygdala and hippocampus. The present findings
      provide new insights into how the use of cocaine during adolescent development
      may modulate emotional behavior later in life. Compromised ability to recognize
      and deal with potential threats is an important risk factor to perpetuate
      compulsive drug seeking and relapse susceptibility.

PMID- 25048000
TI  - Human papillomavirus-related psychosocial impact of patients with genital warts
      in China: a hospital-based cross-sectional study.
AB  - BACKGROUND: Genital warts (GW) are the most common sexually transmitted
      infections. To date, few studies using a human papillomavirus (HPV)-specific
      questionnaire have focused on the impact of quality of life (QoL) among patients
      with GW in developing countries. The origins of GW related psychosocial burdens
      and variations between genders were poorly characterized as well. METHODS: A
      hospital-based survey was conducted in Beijing and Nanjing of China in 2008.
      Eligible patients aged 18-65 who had a diagnosis of GW within 3 months were
      recruited. Demographic information, HPV knowledge, and assessment of psychosocial
      burden were collected by the HPV Impact Profile (HIP). The HIP examined 7
      specific psychosocial domains by 29 items: (1) worries and concerns, (2)
      emotional impact, (3) sexual impact, (4) self-image, (5) partner and
      transmission, (6) interactions with physicians, and (7) control/life impact. HIP
      scores are reversely relates to the subjects' QoL, by which a higher score
      indicating a heavier psychosocial burden. RESULTS: Patients with GW experienced
      heavier psychosocial burdens than those of the general population, and females
      experienced heavier burdens than males (male vs. female: 49.20 vs.51.38, P <
      0.001). "Self Image" and "Sexual Impact" were the two domains that affected
      patients the most, with mean HIP scores of 63.09 and 61.64, respectively. Women
      suffered heavier psychosocial burdens than men in the domain of "Worries and
      Concerns" (female vs. male: 54.57 vs. 42.62, P < 0.001), but lower psychosocial
      burdens in the domains of "Sexual Impact" (female vs. male: 59.16 vs. 65.26, P <
      0.001) and "Interactions with Doctors" (female vs. male: 34.40 vs. 41.97, P <
      0.001). Patients from Nanjing suffered a higher psychosocial burden than those of
      Beijing, especially in domains of "Emotional Impact", "Sexual Impact", "Partner
      and Transmission", and "Interactions with Doctors". CONCLUSIONS: Patients with GW
      suffered heavy psychological burden, and self-image and sexual-related concern
      were the primary cause of burdens. It's important to change the current
      biomedical model to bio-psycho-social model, and establish psychosocial support
      systems. The distinctions of origins of psychosocial burden between genders
      identified will be informative for prevention of GW and control efforts in China
      and other similar settings.

PMID- 25048001
TI  - Why are cortical GABA neurons relevant to internal focus in depression? A cross
      level model linking cellular, biochemical and neural network findings.
AB  - Major depression is a complex and severe psychiatric disorder whose
      symptomatology encompasses a critical shift in awareness, especially in the
      balance from external to internal mental focus. This is reflected by unspecific
      somatic symptoms and the predominance of the own cognitions manifested in
      increased self-focus and rumination. We posit here that sufficient empirical data
      has accumulated to build a coherent biologic model that links these psychologic
      concepts and symptom dimensions to observed biochemical, cellular, regional and
      neural network deficits. Specifically, deficits in inhibitory gamma-aminobutyric
      acid regulating excitatory cell input/output and local cell circuit processing of
      information in key brain regions may underlie the shift that is observed in
      depressed subjects in resting-state activities between the perigenual anterior
      cingulate cortex and the dorsolateral prefrontal cortex. This regional dysbalance
      translates at the network level in a dysbalance between default-mode and
      executive networks, which psychopathologically surfaces as a shift in focus from
      external to internal mental content and associated symptoms. We focus here on
      primary evidence at each of those levels and on putative mechanistic links
      between those levels. Apart from its implications for neuropsychiatric disorders,
      our model provides for the first time a set of hypotheses for cross-level
      mechanisms of how internal and external mental contents may be constituted and
      balanced in healthy subjects, and thus also contributes to the neuroscientific
      debate on the neural correlates of consciousness. 

PMID- 25048002
TI  - No association between RORA polymorphisms and PTSD in two independent samples.

PMID- 25048004
TI  - Proteomic and genomic evidence implicates the postsynaptic density in
      schizophrenia.
AB  - The postsynaptic density (PSD) contains a complex set of proteins of known
      relevance to neuropsychiatric disorders, and schizophrenia specifically. We
      enriched for this anatomical structure, in the anterior cingulate cortex, of 20
      schizophrenia samples and 20 controls from the Stanley Medical Research
      Institute, and used unbiased shotgun proteomics incorporating label-free
      quantitation to identify differentially expressed proteins. Quantitative
      investigation of the PSD revealed more than 700 protein identifications and 143
      differentially expressed proteins. Prominent among these were altered expression
      of proteins involved in clathrin-mediated endocytosis (CME) (Dynamin-1, adaptor
      protein 2) and N-methyl-D-aspartate (NMDA)-interacting proteins such as CYFIP2,
      SYNPO, SHANK3, ESYT and MAPK3 (all P<0.0015). Pathway analysis of the
      differentially expressed proteins implicated the cellular processes of
      endocytosis, long-term potentiation and calcium signaling. Both single-gene and
      gene-set enrichment analyses in genome-wide association data from the largest
      schizophrenia sample to date of 13,689 cases and 18,226 controls show significant
      association of HIST1H1E and MAPK3, and enrichment of our PSD proteome. Taken
      together, our data provide robust evidence implicating PSD-associated proteins
      and genes in schizophrenia, and suggest that within the PSD, NMDA-interacting and
      endocytosis-related proteins contribute to disease pathophysiology.

PMID- 25048003
TI  - All the world's a (clinical) stage: rethinking bipolar disorder from a
      longitudinal perspective.
AB  - Psychiatric disorders have traditionally been classified using a static,
      categorical approach. However, this approach falls short in facilitating
      understanding of the development, common comorbid diagnoses, prognosis and
      treatment of these disorders. We propose a 'staging' model of bipolar disorder
      that integrates genetic and neural information with mood and activity symptoms to
      describe how the disease progresses over time. From an early, asymptomatic, but
      'at-risk' stage to severe, chronic illness, each stage is described with
      associated neuroimaging findings as well as strategies for mapping genetic risk
      factors. Integrating more biologic information relating to cardiovascular and
      endocrine systems, refining methodology for modeling dimensional approaches to
      disease and developing outcome measures will all be crucial in examining the
      validity of this model. Ultimately, this approach should aid in developing
      targeted interventions for each group that will reduce the significant morbidity
      and mortality associated with bipolar disorder. 

PMID- 25048008
TI  - Reliability and validity of five radiographic dental-age estimation methods in a
      population of Malaysian children.
AB  - OBJECTIVE: To evaluate the reliability and validity of Demirjian's, Willems,
      Nolla's, Haavikko's, and Cameriere's radiographic methods of dental-age
      estimation in a population of Malaysian children. METHODS: A total of 426 dental
      panoramic radiographs of 5-15-year-old Malaysian children were included in the
      study. The mean age error and absolute age error for all the methods were
      calculated and their usability analyzed. RESULTS: The Nolla, Willems. and
      Demirjian methods overestimated the dental age with a mean of 0.97, 0.54, and
      0.54 years, respectively, while the Cameriere and Haavikko methods underestimated
      by 0.41 and 1.31 years, respectively. The Cameriere method was highly precise and
      accurate in the population of Malaysian children, whereas the Haavikko and
      Demirjian methods were the least precise and accurate. CONCLUSIONS: The Cameriere
      method of dental-age estimation is highly valid and reliable for Malaysian
      population, followed by the Willems and Nolla methods.

PMID- 25048005
TI  - The neurobiology and treatment of first-episode schizophrenia.
AB  - It is evident that once psychosis is present in patients with schizophrenia, the
      underlying biological process of the illness has already been ongoing for many
      years. At the time of diagnosis, patients with schizophrenia show decreased mean
      intracranial volume (ICV) as compared with healthy subjects. Since ICV is driven
      by brain growth, which reaches its maximum size at approximately 13 years of age,
      this finding suggests that brain development in patients with schizophrenia is
      stunted before that age. The smaller brain volume is expressed as decrements in
      both grey and white matter. After diagnosis, it is mainly the grey matter loss
      that progresses over time whereas white matter deficits are stable or may even
      improve over the course of the illness. To understand the possible causes of the
      brain changes in the first phase of schizophrenia, evidence from treatment
      studies, postmortem and neuroimaging investigations together with animal
      experiments needs to be incorporated. These data suggest that the pathophysiology
      of schizophrenia is multifactorial. Increased striatal dopamine synthesis is
      already evident before the time of diagnosis, starting during the at-risk mental
      state, and increases during the onset of frank psychosis. Cognitive impairment
      and negative symptoms may, in turn, result from other abnormalities, such as NMDA
      receptor hypofunction and low-grade inflammation of the brain. The latter two
      dysfunctions probably antedate increased dopamine synthesis by many years,
      reflecting the much earlier presence of cognitive and social dysfunction.
      Although correction of the hyperdopaminergic state with antipsychotic agents is
      generally effective in patients with a first-episode psychosis, the effects of
      treatments to correct NMDA receptor hypofunction or low-grade inflammation are
      (so far) rather modest at best. Improved efficacy of these interventions can be
      expected when they are applied at the onset of cognitive and social dysfunction,
      rather than at the onset of psychosis. 

PMID- 25048007
TI  - Berberine protects homocysteic acid-induced HT-22 cell death: involvement of Akt
      pathway.
AB  - Berberine (BBR), one of the major constituents of Chinese herb Rhizoma coptidis,
      has been reported to exert beneficial effects to various diseases, including
      Alzheimer's disease (AD). In the present work, we aimed to investigate the
      effects of BBR on neuronal cell death induced by homocysteic acid (HCA), which
      was considered as a risk of AD. BBR significantly reduced HCA-induced reactive
      oxygen species (ROS) generation, lactate dehydrogenase release and subsequent
      cell death. LY294002, the PI3K inhibitor, blocked the protection as well as the
      up-regulation of Akt phosphorylation of BBR. Taken together, our results indicate
      that BBR protects HCA-induced HT-22 cell death partly via modulating Akt pathway,
      suggesting BBR may be a promising therapeutic agent for the treatment of HCA
      related diseases, including AD. 

PMID- 25048006
TI  - Disturbed cingulate glutamate metabolism in adults with high-functioning autism
      spectrum disorder: evidence in support of the excitatory/inhibitory imbalance
      hypothesis.
AB  - Over the last few years, awareness of autism spectrum disorder (ASD) in adults
      has increased. The precise etiology of ASD is still unresolved. Animal research,
      genetic and postmortem studies suggest that the glutamate (Glu) system has an
      important role, possibly related to a cybernetic imbalance between neuronal
      excitation and inhibition. To clarify the possible disruption of Glu metabolism
      in adults with high-functioning autism, we performed a magnetic resonance
      spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and
      the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients
      with high-functioning ASD and 29 carefully matched healthy volunteers underwent
      MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic
      data were compared between groups and were correlated with psychometric measures
      of autistic features. We found a significant decrease in the cingulate N-acetyl
      aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with
      ASD, whereas we did not find other metabolic abnormalities in the ACC or the
      cerebellum. The Glx signal correlated significantly with psychometric measures of
      autism, particularly with communication deficits. Our data support the hypothesis
      that there is a link between disturbances of the cingulate NAA and Glx
      metabolism, and autism. The findings are discussed in the context of the
      hypothesis of excitatory/inhibitory imbalance in autism. Further research should
      clarify the specificity and dynamics of these findings regarding other
      neuropsychiatric disorders and other brain areas. 

PMID- 25048009
TI  - Hg(2+) -induced in situ generated radical cation of (S)-BINOL-based polymer for
      highly enantioselective recognition of phenylalaninol.
AB  - Phenylalaninol enantiomers are one of the most important chiral compounds due to
      its presence in biologically active molecules and pharmaceutical products. In
      this paper, a novel chiral fluorescence polymer sensor incorporating (S)-BINOL
      and oligomeric aniline via a nucleophilic addition-elimination reaction is
      designed and synthesized. Polymer sensor exhibits "turn-off" fluorescence
      quenching response upon the addition of Hg(2+) , and "turn-on" moderate
      fluorescence enhancement behavior towards phenylalaninol enantiomers. Meanwhile,
      this kind of (S)-BINOL-based polymer sensor can exhibit highly selective
      enantioselective recognition response towards (L)-phenylalaninol upon the
      addition of Hg(2+) and the value of ef can reach as high as 5.4, which can be
      attributed to the formation of in situ generated radical cation arisen from
      oligomeric aniline moiety by Hg(2+) induction. 

PMID- 25048012
TI  - Asymmetric borylation of alpha,beta-unsaturated esters catalyzed by novel ring
      expanded N-heterocyclic carbenes based on chiral 3,4-dihydro-quinazolinium
      compounds.
AB  - A series of chiral 6-membered ring N-heterocyclic carbene (NHC) precursors based
      on 3,4-dihydro-quinazoline were synthesized with overall yields of 54-62%. NHCs
      generated from these precursors show excellent asymmetric catalytic properties
      for borylation of alpha,beta-unsaturated esters with enantioselectivity of up to
      93% with a catalyst content of only 1 mol%. 

PMID- 25048011
TI  - Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast
      cultures and reduces numbers of osteoclasts in mouse marrow cultures.
AB  - SUMMARY: The basic mechanisms by which strontium ranelate acts on bone are still
      unclear. We show that an important action of strontium salts is to block
      calcification in cultures of osteoblasts, the bone-forming cells. These results
      suggest that strontium treatment could have previously overlooked effects on
      bone. INTRODUCTION: The basic mechanisms of action of strontium ranelate (SrR) on
      bone have remained unclear. We studied the direct actions of Sr(2+) salts in
      functional cultures of osteoblasts and osteoclasts. METHODS: Cultures of primary
      osteoblasts from rat calvariae and osteoclast-forming mouse marrow cells were
      treated continuously with either SrR or strontium chloride (SrCl2). RESULTS:
      Abundant, discretely mineralised 'trabecular' bone structures formed in control
      osteoblast cultures after 14 days. SrR at 0.01, 0.1 and 1 mM inhibited
      mineralisation to 59, 98 and 100 % (all p < 0.001) of control values,
      respectively. SrCl2 at the same concentrations caused similar inhibitions.
      Osteoblast cell numbers and alkaline phosphatase activity were unaltered. SrR
      dose-dependently reduced the formation of multinucleated osteoclasts from marrow
      mononuclear cells cultured on dentine for 8 days in the presence of macrophage
      colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa
      B ligand (RANKL), with a 50 % inhibition occurring at 1 mM; SrCl2 was slightly
      less effective, eliciting a maximal 30 % inhibition. Corresponding decreases in
      total resorption pit formation were observed, suggesting Sr(2+) salts affect
      osteoclast formation rather than resorptive activity. CONCLUSION: Our findings
      are consistent with the documented physicochemical inhibitory action of Sr(2+) on
      mineralisation but contrast with reports that Sr(2+) increases osteoblast
      activity and number in vitro. Our results suggest that rather than acting as an
      agent that 'uncouples' bone formation and resorption, Sr(2+) acts as a global
      inhibitor of bone cell function, with particularly marked effects on
      mineralisation. The potential effects of long-term Sr(2+) on secondary
      mineralisation in bone deserve investigation.

PMID- 25048010
TI  - Environmental triggers for IBD.
AB  - The fundamental elucidation of how environmental influences provoke the
      initiation of disease as well as flares of inflammatory bowel disease (IBD)
      remains incomplete. The current understanding of these diseases suggests that
      ulcerative colitis (UC) and Crohn's disease (CD) result from poorly defined
      interactions between genetic and environmental factors which culminate in the
      pathologic effects and clinical manifestations of these diseases. The genetic
      variant appears not sufficient itself to lead to the development of the clinical
      disease, but likely must combine with the environmental factors. The intestinal
      microbiome is pivotal to IBD development. A greater understanding of the
      contribution of these factors to dysbiosis is critical, and we aspire to
      restoring a healthy microbiome to treat flares and ideally prevent the
      development of IBD and its complications. This article aims to place the
      environmental influences in the context of their potential contribution to the
      development of the pathophysiology of IBD. 

PMID- 25048013
TI  - A label-free bioluminescent sensor for real-time monitoring polynucleotide kinase
      activity.
AB  - Polynucleotide kinase (PNK) plays a crucial role in maintaining the genomic
      stability of cells and is becoming a potential target in the radio-therapeutic
      treatment of cancers. The fluorescent method is usually used to measure the PNK
      activity, but it is impossible to obtain the real-time monitoring without the
      employment of the labeled DNA probes. Here, we report a label-free bioluminescent
      sensor for PNK activity assay through real-time monitoring of the phosphorylation
      dependent DNA ligation reaction. In this bioluminescent sensor, two hairpin DNA
      probes with 5'-protruding terminal are designed as the phosphate acceptor, and
      the widely used phosphate donor of ATP is substituted by dCTP. In the absence of
      PNK, the ligation reaction cannot be triggered due to the lack of 5'-phosphoryl
      groups in the probes, and the background signal is negligible. With the addition
      of PNK, the phosphorylation-ligation reaction of the probes is initiated with the
      release of AMP, and the subsequent conversion of AMP to ATP leads to the
      generation of distinct bioluminescence signal. The PNK activity assay can be
      performed in real time by continuously monitoring the bioluminescence signal.
      This bioluminescent sensor is much simpler, label-free, cost-effective, and free
      from the autofluorescence interference of biological matrix, and can be further
      used for quantitative, kinetic, and inhibition assay. 

PMID- 25048014
TI  - Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and
      associated problems in rats.
AB  - Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this
      study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced
      hyperthyroidism considering laboratory rat as a model. Alterations in the serum
      concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation
      (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants
      such as superoxide dismutase, catalase and glutathione and in serum total
      cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate
      transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea
      were evaluated. Administration of l-T4 (500-ug kg(-1) body weight) enhanced not
      only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and
      urea with a parallel decrease in the levels of antioxidants and serum lipids.
      However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all
      these adverse effects were ameliorated, indicating the potential of PQQ in the
      amelioration of hyperthyroidism and associated problems. Possibly, the curative
      effects were mediated through inhibition of oxidative stress. We suggest that PQQ
      may be considered for therapeutic use for hyperthyroidism after dose
      standardization.

PMID- 25048015
TI  - Leptospira-rat-human relationship in Luzon, Philippines.
AB  - Leptospirosis is a zoonotic infection that is caused by the pathogenic species of
      Leptospira. Rats are the most important reservoirs of these organisms. Our study
      aimed to characterize Leptospira isolates from humans and rats and elucidate the
      Leptospira-rat-human relationship in Luzon, Philippines. Forty strains were
      isolated from humans and rats. The isolates were confirmed to be Leptospira and
      pathogenic through rrl- and flaB-PCR, respectively. Around 73% of the isolates
      were found to be lethal to hamsters. Serotyping showed that there were mainly
      three predominant leptospiral serogroups in the study areas namely Pyrogenes,
      Bataviae, and Grippotyphosa. Gyrase B gene sequence analysis showed that all the
      isolates belonged to Leptospira interrogans. Most had 100% similarity with
      serovar Manilae (15/40), serovar Losbanos (8/40), and serogroup Grippotyphosa
      (8/40). Strains from each group had highly identical pulsed-field gel
      electrophoresis patterns and were further grouped as A (Pyrogenes, 14), B
      (Bataviae, 8), and C (Grippotyphosa, 10). Results further revealed that similar
      serotypes were isolated from both humans and rats in the same areas. It is
      suggested that these three predominant groups with highly similar intra-group
      PFGE patterns may have been primarily transmitted by rats and persistently caused
      leptospirosis in humans particularly in the Luzon islands. 

PMID- 25048016
TI  - Anti-tumor effect of polysaccharides from Scutellaria barbata D. Don on the 95-D
      xenograft model via inhibition of the C-met pathway.
AB  - Polysaccharides isolated from Scutellaria barbata (PSB) have been reported to
      have anti-tumor effects. To investigate the underlying mechanism, a highly
      invasive, metastatic and phospho-c-Met overexpression lung carcinoma cell, 95-D
      cell line was used. The results showed that in vitro, PSB not only could inhibit
      the proliferation of 95-D cell line (IC(50) = 35.2 MUg/mL), but also down
      regulated the expression of phospho-c-Met and its downstream signaling molecules
      including phospho-Erk and phospho-Akt. In vivo, PSB inhibited tumor growth in the
      95-D subcutaneous xenograft model in a dose-dependent manner; after once-daily
      intraperitoneal injection for 3 weeks, tumor growth inhibition T/C ratio for 100
      and 200 mg/kg treatments was 42.72% and 13.6%, respectively. In the end of the in
      vivo study, tumor tissues were harvested for further evaluation of the
      phosphorylation level of c-Met, AKT, and ERK. Ex vivo results demonstrated that
      the phosphorylation of c-Met and its downstream signaling molecules were also
      significantly inhibited by PSB. Immunohistochemistry analysis showed dose
      dependent inhibition of tumor cell proliferation (Ki67) and reduction of
      microvessel density (CD31). In summary, the results indicated that PSB exerted
      anti-tumor growth activity on human lung cancer 95-D in vitro and in vivo by
      directly regulating the c-Met signaling pathway and the anti-tumor effects were
      mainly based on its anti-proliferation and anti-angiogenesis action.

PMID- 25048017
TI  - Overexpression of PEP-19 suppresses angiotensin II-induced cardiomyocyte
      hypertrophy.
AB  - The precise molecular mechanisms leading to disturbance of Ca(2+)/calmodulin
      dependent intracellular signalling in cardiac hypertrophy remains unclear. As an
      endogenous calmodulin regulator protein, the pathophysiology role of PEP-19
      during cardiac hypertrophy was investigated in the present study. We here
      demonstrated that PEP-19 protein levels are significantly elevated in the aortic
      banding model in vivo and angiotensin II-induced cardiomyocyte hypertrophy in
      vitro. Consistent with inhibitory actions of PEP-19 on cardiomyocyte hypertrophy,
      induction of CaMKII and calcineurin activation as well as hypertrophy-related
      genes including atrial natriuretic peptide (ANP) and brain natriuretic peptide
      (BNP) was significantly inhibited by PEP-19 transfection. Moreover, PEP-19
      partially ameliorates angiotensin II-induced elevation of phospho-phospholamban
      (Thr-17) and sarcoplasmic reticulum Ca(2+) release in cardiomyocytes. Together,
      our results suggest that PEP-19 attenuates angiotensin II-induced cardiomyocyte
      hypertrophy via suppressing the disturbance of CaMKII and calcineurin signaling. 

PMID- 25048018
TI  - Inhibition of smooth muscle cell proliferation by ezetimibe via the cyclin D1
      MAPK pathway.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) contributes to the
      development of atherosclerosis. Ezetimibe is a new lipid lowering agent that
      inhibits cholesterol absorption. In the present study we attempted to investigate
      whether ezetimibe has any effect on VSMC proliferation and the potential
      mechanisms involved. Our data showed ezetimibe abrogated the proliferation and
      migration of primary rat VSMCs induced by Chol:MbetaCD. Mechanically, we found
      that ezetimibe was capable of abolishing cyclin D1, CDK2, phospho-Rb (p-Rb), and
      E2F protein expressions that were upregulated by Chol:MbetaCD treatment. In
      addition, Ezetimibe was able to reverse cell cycle progression induced by
      Chol:MbetaCD, which was further supported by its down-regulation of cyclin D1
      promoter activity in the presence of Chol:MbetaCD. Furthermore, ezetimibe
      abrogated the increment of phospho-ERK1/2 (p-ERK1/2) and nuclear accumulation of
      ERK1/2 in VSMCs induced by Chol:MbetaCD. Inhibition of the MAPK pathway by using
      ERK1/2 inhibitor PD98059 attenuated the reduction effect of ezetimibe on the
      expressions of phosphor-MEK1 (p-MEK1), p-ERK1/2, and cyclin D1. Taken together
      our data suggest that ezetimibe inhibits Chol:MbetaCD-induced VSMCs proliferation
      and leads to cell cycle arrest at the G0/G1 phase by suppressing cyclin D1
      expression via the MAPK signaling pathway. These novel findings support the
      potential pleiotropic effect of ezetimibe in cardiovascular disease. 

PMID- 25048019
TI  - Oleuropein induced apoptosis in HeLa cells via a mitochondrial apoptotic cascade
      associated with activation of the c-Jun NH2-terminal kinase.
AB  - Oleuropein could inhibit growth and/or induce apoptosis in several cancer cell
      lines. In this study, we investigate how oleuropein strongly induces apoptotic
      cell death in HeLa human cervical carcinoma cells. Oleuropein induced HeLa cells
      apoptosis as demonstrated by induction of a sub-G(1) peak in flow cytometry and
      apoptosis-related morphological changes observed by fluorescence microscopy after
      being stained by Hoechst 33324. The results also showed that 150 - 200 MUM
      oleuropein&ndash;treated HeLa cells were arrested at the G(2)/M phase. Western
      blot analysis revealed that the phosphorylated ATF-2, c-Jun NH(2)-terminal kinase
      (JNK) protein, p53, p21, Bax, and cytochrome c protein in the cytoplasm
      significantly increased in a dose-dependent manner after treatment of oleuropein
      for 24 h. Additionally, increasing levels of Bax in response to JNK/SPAK
      signaling, which formed mitochondrial membrane channels, accounted for releasing
      of cytochrome c and activation of caspase-9 and -3. SP600125 (20 MUM), a JNK(1/2)
      inhibitor, markedly suppressed the formation of apoptotic bodies and JNK
      activation induced by oleuropein at 200 MUM. Thus, oleuropein-induced apoptosis
      was activated by the JNK/SPAK signal pathway. The result shows that oleuropein
      holds promise as a potential chemotherapeutic agent for the treatment of HeLa
      cells.

PMID- 25048020
TI  - Timing of circadian genes in mammalian tissues.
AB  - Circadian clocks are endogenous oscillators driving daily rhythms in physiology.
      The cell-autonomous clock is governed by an interlocked network of
      transcriptional feedback loops. Hundreds of clock-controlled genes (CCGs)
      regulate tissue specific functions. Transcriptome studies reveal that different
      organs (e.g. liver, heart, adrenal gland) feature substantially varying sets of
      CCGs with different peak phase distributions. To study the phase variability of
      CCGs in mammalian peripheral tissues, we develop a core clock model for mouse
      liver and adrenal gland based on expression profiles and known cis-regulatory
      sites. 'Modulation factors' associated with E-boxes, ROR-elements, and D-boxes
      can explain variable rhythms of CCGs, which is demonstrated for differential
      regulation of cytochromes P450 and 12 h harmonics. By varying model parameters we
      explore how tissue-specific peak phase distributions can be generated. The
      central role of E-boxes and ROR-elements is confirmed by analysing ChIP-seq data
      of BMAL1 and REV-ERB transcription factors.

PMID- 25048021
TI  - Differential regulation of cytokinin oxidase genes and cytokinin-induced auxin
      biosynthesis by cellular cytokinin level in transgenic poplars.
AB  - KEY MESSAGE: The present work with transgenic poplar lines producing varying
      levels of trans -zeatin suggests the existence of a switching threshold for
      triggering ckx gene expression or suppressing cytokinin-induced auxin. Cytokinins
      have an important role in growth and developmental processes of plants.
      Transgenic plants with varying levels of cellular cytokinin are convenient tools
      for studying its role in morphogenetic as well as molecular responses. In this
      work, the transgenic lines producing either high level of cellular trans-zeatin
      (HX lines) or moderate level (MX lines) were compared with regard to their
      cytokinin oxidase activities and cellular auxin content. The HX lines showed
      typical cytokinin phenotypes including leafy shoots and spontaneous shoot
      formation on hormone free medium. In contrast, the MX lines did not show any
      striking phenotypes. However, in leaf disk culture on hormone free medium, they
      regenerated roots and subsequently formed shoots from the roots. Determination of
      cellular IAA content revealed a significant increase in the level in MX lines but
      not in HX lines. Of nine cytokinin oxidase genes (ckx) examined by qPCR, five
      were activated in HX lines but not in MX lines. Among them, ckx4 appeared to play
      a key role in maintaining cellular cytokinin level since it showed more than
      1,000-fold increase in HX lines and in the leaf disks of untransformed control
      exposed to exogenous cytokinins. Although low level of cellular cytokinin did not
      induce the expression of ckx genes, it appeared to trigger cellular IAA
      biosynthesis.

PMID- 25048022
TI  - Improved expression of recombinant plant-made hEGF.
AB  - KEY MESSAGE: The yield of recombinant hEGF was increased approximately tenfold
      through a range of optimisations. Further, the recombinant protein was found to
      have biological activity comparable to commercial hEGF. Human epidermal growth
      factor (hEGF) is a powerful mitogen that can enhance the healing of a wide range
      of injuries, including burns, cuts, diabetic ulcers and gastric ulcers. However,
      despite its clinical value, hEGF is only consistently used for the treatment of
      chronic diabetic ulcers due to its high cost. In this study, hEGF was transiently
      expressed in Nicotiana benthamiana plants and targeted to the apoplast, ER and
      vacuole. Several other approaches were also included in a stepwise fashion to
      identify the optimal conditions for the expression of recombinant hEGF.
      Expression was found to be highest in the vacuole, while targeting hEGF to the ER
      caused a decrease in total soluble protein (TSP). Using a codon optimised
      sequence was found to increase vacuolar targeted hEGF yield by ~34 %, while it
      was unable to increase the yield of ER targeted hEGF. The use of the P19
      silencing inhibitor was able to further increase expression by over threefold,
      and using 5-week-old plants significantly increased expression compared to 4- or
      6-week-old-plants. The combined effect of these optimisations increased
      expression tenfold over the initial apoplast targeted construct to an average
      yield of 6.24 % of TSP. The plant-made hEGF was then shown to be equivalent to
      commercial E. coli derived hEGF in its ability to promote the proliferation of
      mouse keratinocytes. This study supports the potential for plants to be used for
      the commercial production of hEGF, and identifies a potential limitation for the
      further improvement of recombinant protein yields.

PMID- 25048024
TI  - A review of fMRI simulation studies.
AB  - Simulation studies that validate statistical techniques for fMRI data are
      challenging due to the complexity of the data. Therefore, it is not surprising
      that no common data generating process is available (i.e. several models can be
      found to model BOLD activation and noise). Based on a literature search, a
      database of simulation studies was compiled. The information in this database was
      analysed and critically evaluated focusing on the parameters in the simulation
      design, the adopted model to generate fMRI data, and on how the simulation
      studies are reported. Our literature analysis demonstrates that many fMRI
      simulation studies do not report a thorough experimental design and almost
      consistently ignore crucial knowledge on how fMRI data are acquired. Advice is
      provided on how the quality of fMRI simulation studies can be improved. 

PMID- 25048023
TI  - A wheat aminocyclopropane-1-carboxylate oxidase gene, TaACO1, negatively
      regulates salinity stress in Arabidopsis thaliana.
AB  - KEY MESSAGE: TaACO1 could catalyze ACC into ethylene in vitro. Constitutive
      expression of TaACO1 in Arabidopsis conferred salt sensitivity, and TaACO1
      regulates salt stress mainly via the DREB1/CBF signal transduction pathway.
      Ethylene signaling plays essential roles in mediating plant responses to biotic
      and abiotic stresses, besides regulating plant growth and development. The roles
      of ethylene biosynthesis in abiotic stress, however, remain elusive. In this
      study, an aminocyclopropane-1-carboxylate oxidase gene, TaACO1, affecting the
      terminal step in ethylene biosynthesis, was isolated from a salt-tolerant bread
      wheat introgression line Shanrong No. 3 (SR3) and its effect on salt-stress
      response was examined. Purified recombinant protein of TaACO1 heterogenously
      expressed in Escherchia coli could catalyze ACC into ethylene in vitro. TaACO1
      transcripts were down-regulated by salt, drought, oxidative stress and ABA.
      TaACO1-transgenic plants conferred salt sensitivity as judged from the seed
      germination, cotyledon greening and the relative root growth under salt stress.
      Constitutive expression of TaACO1 in Arabidopsis increased AtMYB15 expression and
      suppressed the expression of stress-responsive genes AtRAB18, AtCBF1 and AtCBF3.
      These findings are helpful in understanding the roles of ethylene biosynthesis in
      plant salt-stress response.

PMID- 25048025
TI  - De novo assembly and transcriptome analysis of the rubber tree (Hevea
      brasiliensis) and SNP markers development for rubber biosynthesis pathways.
AB  - Hevea brasiliensis (Willd. Ex Adr. Juss.) Muell.-Arg. is the primary source of
      natural rubber that is native to the Amazon rainforest. The singular properties
      of natural rubber make it superior to and competitive with synthetic rubber for
      use in several applications. Here, we performed RNA sequencing (RNA-seq) of H.
      brasiliensis bark on the Illumina GAIIx platform, which generated 179,326,804 raw
      reads on the Illumina GAIIx platform. A total of 50,384 contigs that were over
      400 bp in size were obtained and subjected to further analyses. A similarity
      search against the non-redundant (nr) protein database returned 32,018 (63%)
      positive BLASTx hits. The transcriptome analysis was annotated using the clusters
      of orthologous groups (COG), gene ontology (GO), Kyoto Encyclopedia of Genes and
      Genomes (KEGG), and Pfam databases. A search for putative molecular marker was
      performed to identify simple sequence repeats (SSRs) and single nucleotide
      polymorphisms (SNPs). In total, 17,927 SSRs and 404,114 SNPs were detected.
      Finally, we selected sequences that were identified as belonging to the
      mevalonate (MVA) and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathways, which
      are involved in rubber biosynthesis, to validate the SNP markers. A total of 78
      SNPs were validated in 36 genotypes of H. brasiliensis. This new dataset
      represents a powerful information source for rubber tree bark genes and will be
      an important tool for the development of microsatellites and SNP markers for use
      in future genetic analyses such as genetic linkage mapping, quantitative trait
      loci identification, investigations of linkage disequilibrium and marker-assisted
      selection. 

PMID- 25048028
TI  - Neural basis of anticipatory anxiety reappraisals.
AB  - Reappraisal is a well-known emotion regulation strategy. Recent neuroimaging
      studies suggest that reappraisal recruits both medial and lateral prefrontal
      brain regions. However, few studies have investigated neural representation of
      reappraisals associated with anticipatory anxiety, and the specific nature of the
      brain activity underlying this process remains unclear. We used functional
      magnetic resonance imaging (fMRI) to investigate neural activity associated with
      reappraisals of transient anticipatory anxiety. Although transient anxiety
      activated mainly subcortical regions, reappraisals targeting the anxiety were
      associated with increased activity in the medial and lateral prefrontal regions
      (including the orbitofrontal and anterior cingulate cortices). Reappraisal
      decreased fear circuit activity (including the amygdala and thalamus).
      Correlational analysis demonstrated that reductions in subjective anxiety
      associated with reappraisal were correlated with orbitofrontal and anterior
      cingulate cortex activation. Reappraisal recruits medial and lateral prefrontal
      regions; particularly the orbitofrontal and anterior cingulate cortices are
      associated with successful use of this emotion regulation strategy. 

PMID- 25048029
TI  - Temporomandibular joint replacement periprosthetic joint infections: a review of
      early diagnostic testing options.
AB  - The incidence of a periprosthetic joint infection is uncommon after total joint
      replacement. Since the clinical, psychological, and economic consequences of this
      complication are substantial, the development of management algorithms based on
      early diagnostic testing has been the subject of continued exploration in the
      orthopaedic literature. While there has been discussion of this topic in the
      total temporomandibular joint replacement literature and preliminary management
      algorithms have been established, no diagnostic testing protocols have been
      proposed or studied for the management of early and/or late periprosthetic joint
      infections. This paper will review the classification of periprosthetic joint
      infections, the associated risk factors, the clinical sensitivity and specificity
      of laboratory and imaging diagnostic studies and their utility in the management
      of early and late onset orthopaedic periprosthetic joint infections. This review
      may provide an initial framework for the use of early diagnostic testing for the
      management of total temporomandibular joint replacement periprosthetic joint
      infections and stimulate further investigation into this topic.

PMID- 25048026
TI  - Amyotrophic lateral sclerosis outcome measures and the role of albumin and
      creatinine: a population-based study.
AB  - IMPORTANCE: There is an urgent need to identify reliable biomarkers of
      amyotrophic lateral sclerosis (ALS) progression for clinical practice and
      pharmacological trials. OBJECTIVES: To correlate several hematological markers
      evaluated at diagnosis with ALS outcome in a population-based series of patients
      (discovery cohort) and replicate the findings in an independent validation cohort
      from an ALS tertiary center. DESIGN, SETTING, AND PARTICIPANTS: The discovery
      cohort included 712 patients with ALS from the Piemonte and Valle d'Aosta
      Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31,
      2011. The validation cohort comprised 122 patients with ALS at different stages
      of disease consecutively seen at an ALS tertiary center between January 1, 2007,
      and January 1, 2009. MAIN OUTCOMES AND MEASURES: The following hematological
      factors were investigated and correlated with survival: total leukocytes,
      neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin,
      bilirubin, total cholesterol, triglycerides, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid
      stimulating hormones, and erythrocyte sedimentation rate; all analyses were
      performed separately by sex. The patient of the validation cohort also underwent
      bioelectrical impedance analysis for the calculation of fat-free mass. RESULT: Of
      the 712 patients in the examined period in Piemonte and Valle d'Aosta, 638
      (89.6%) were included in the study. Only serum albumin (men: <= 4.3 vs >4.3
      mg/dL, P < .001; women: <= 4.3 vs >4.3 mg/dL, P < .001) and creatinine levels
      (men: <= 0.82 vs >0.82 mg/dL, P = .004; women: <= 0.65 vs >0.05 mg/dL, P = .004)
      and lymphocyte count (men: <= 1700 vs >1700/MUL, P = .04; women: <= 1700 vs
      >1700/MUL, P = .02) were significantly associated with ALS outcome in both sexes
      with a dose-response effect (better survival with increasing levels). These
      findings were confirmed in the validation cohort. Multivariable analysis showed
      that serum albumin (men: hazard ratio [HR], 1.39; 95% CI, 1.05-1.90; P = .02;
      women: HR, 1.73; 95 % CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95%
      CI, 1.11-1.95; P = .007; women: HR, 1.49; 95% CI, 1.07-2.05; P = .02) were
      independent predictors of survival in both sexes; no other hematological factor
      was retained in the model. In patients with ALS, serum albumin was correlated
      with markers of inflammatory state while serum creatinine was correlated with fat
      free mass, which is a marker of muscle mass. CONCLUSIONS AND RELEVANCE: In ALS,
      serum albumin and creatinine are independent markers of outcome in both sexes.
      Creatinine reflects the muscle waste whereas albumin is connected with
      inflammatory state. Both creatinine and albumin are reliable markers of the
      severity of clinical status in patients with ALS and can be used in defining
      prognosis at the time of diagnosis.

PMID- 25048030
TI  - Design and synthesis of mono and bicyclic tetrapeptides thioester as potent
      inhibitor of histone deacetylases.
AB  - Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer
      agents that have an effect on gene regulation. The naturally occurring cyclic
      depsipeptide FK228 containing disulfide and Largazole possessing thioester
      functionalities act as pro-drugs and share the same HDAC inhibition mechanism in
      cell. Inspired from these facts, we have reported bicyclic tetrapeptide disulfide
      HDAC inhibitors resembling FK228 with potent activity and enhanced selectivity.
      In the present study, we report the design and synthesis of several mono and
      bicyclic tetrapeptide thioester HDAC inhibitors that share the inhibition
      mechanism similar to Largazole. Most of the compounds showed HDAC1 and HDAC4
      inhibition and p21 promoting activity in nanomolar ranges. Among these the
      monocyclic peptides 1, 2 and bicyclic peptide, 4 are notable demanding more
      advanced research to be promising anticancer drug candidates.

PMID- 25048031
TI  - Diaryl-substituted azolylthioacetamides: Inhibitor discovery of New Delhi metallo
      beta-lactamase-1 (NDM-1).
AB  - The emergence and spread of antibiotic-resistant pathogens is a global public
      health problem. Metallo-beta-lactamases (MbetaLs) such as New Delhi MbetaL-1 (NDM
      1) are principle contributors to the emergence of resistance because of their
      ability to hydrolyze almost all known beta-lactam antibiotics including
      penicillins, cephalosporins, and carbapenems. A clinical inhibitor of MBLs has
      not yet been found. In this study we developed eighteen new diaryl-substituted
      azolylthioacetamides and found all of them to be inhibitors of the MbetaL L1 from
      Stenotrophomonas maltophilia (Ki < 2 MUM), thirteen to be mixed inhibitors of NDM
      1 (Ki < 7 MUM), and four to be broad-spectrum inhibitors of all four tested
      MbetaLs CcrA from Bacteroides fragilis, NDM-1 and ImiS from Aeromonas veronii,
      and L1 (Ki < 52 MUM), which are representative of the B1a, B1b, B2, and B3
      subclasses, respectively. Docking studies revealed that the azolylthioacetamides,
      which have the broadest inhibitory activity, coordinate to the Zn(II) ion(s)
      preferentially via the triazole moiety, while other moieties interact mostly with
      the conserved active site residues Lys224 (CcrA, NDM-1, and ImiS) or Ser221 (L1).

PMID- 25048032
TI  - Screening for dementia in hospitalized older adults: try the Mini-Cog.

PMID- 25048034
TI  - Diabetes: Gpr120 agonist has anti-inflammatory and insulin-sensitizing effects.

PMID- 25048035
TI  - Diabetes: sustained effects of intensive glucose control in established T2DM.

PMID- 25048033
TI  - Psychological and social work factors as predictors of mental distress: a
      prospective study.
AB  - Studies exploring psychological and social work factors in relation to mental
      health problems (anxiety and depression) have mainly focused on a limited set of
      exposures. The current study investigated prospectively a broad set of specific
      psychological and social work factors as predictors of potentially clinically
      relevant mental distress (anxiety and depression), i.e. "caseness" level of
      distress. Employees were recruited from 48 Norwegian organizations, representing
      a wide variety of job types. A total of 3644 employees responded at both baseline
      and at follow-up two years later. Respondents were distributed across 832
      departments within the 48 organizations. Nineteen work factors were measured. Two
      prospective designs were tested: (i) with baseline predictors and (ii) with
      average exposure over time ([T1+T2]/2) as predictors. Random intercept logistic
      regressions were conducted to account for clustering of the data. Baseline
      "cases" were excluded (n = 432). Age, sex, skill level, and mental distress as a
      continuous variable at T1 were adjusted for. Fourteen of 19 factors showed some
      prospective association with mental distress. The most consistent risk factor was
      role conflict (highest odds ratio [OR] 2.08, 99% confidence interval [CI]: 1.45
      3.00). The most consistent protective factors were support from immediate
      superior (lowest OR 0.56, 99% CI: 0.43-0.72), fair leadership (lowest OR 0.52,
      99% CI: 0.40-0.68), and positive challenge (lowest OR 0.60, 99% CI: 0.41-0.86).
      The present study demonstrated that a broad set of psychological and social work
      factors predicted mental distress of potential clinical relevance. Some of the
      most consistent predictors were different from those traditionally studied. This
      highlights the importance of expanding the range of factors beyond commonly
      studied concepts like the demand-control model and the effort-reward imbalance
      model. 

PMID- 25048036
TI  - Reproductive endocrinology: functional effects of sex hormone-binding globulin
      variants.
AB  - A new study has found eight single nucleotide polymorphisms in sex hormone
      binding globulin that functionally affect its affinity for androgens or estrogens
      and other biochemical properties. This finding adds to growing concern about the
      'one size fits all' approach in formulas to calculate free or bioavailable
      concentrations of estradiol and testosterone.

PMID- 25048038
TI  - Obesity: global trends in the prevalence of overweight and obesity.
AB  - A new report provides compelling evidence of the high prevalence of overweight
      and obesity throughout the world. The prevalence has increased since 1980, but at
      different rates across ages, times and locations. Studies exploring the causes of
      these differences could aid development of effective prevention strategies.

PMID- 25048037
TI  - VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs.
AB  - Systemic administration of antiangiogenic drugs that target components of the
      vascular endothelial growth factor A (VEGF-A; VEGF) signal transduction pathway
      has become a viable therapeutic option for patients with various types of cancer.
      Nevertheless, these drugs can drive alterations in healthy vasculatures, which in
      turn are associated with adverse effects in healthy tissues. VEGF is crucial for
      vascular homeostasis and the maintenance of vascular integrity and architecture
      in endocrine organs. Given these critical physiological functions, systemic
      delivery of drugs that target VEGF signalling can block VEGF-mediated vascular
      functions in endocrine organs, such as the thyroid gland, and lead to endocrine
      dysfunction, including hypothyroidism, adrenal insufficiency and altered insulin
      sensitivity. This Review discusses emerging evidence from preclinical and
      clinical studies that contributes to understanding the mechanisms that underlie
      the vascular changes and subsequent modulations of endocrine function that are
      induced by targeted inhibition of VEGF signalling. Understanding these mechanisms
      is crucial for the design of antiangiogenic drugs with minimal associated adverse
      effects that will enable effective treatment of patients with cancer. 

PMID- 25048039
TI  - AMPK-NF-kappaB axis in the photoreceptor disorder during retinal inflammation.
AB  - Recent progress in molecular analysis has revealed the possible involvement of
      multiple inflammatory signaling pathways in pathogenesis of retinal degeneration.
      However, how aberrant signaling pathways cause tissue damage and dysfunction is
      still being elucidated. Here, we focus on 5'-adenosine monophosphate (AMP)
      activated protein kinase (AMPK), originally recognized as a key regulator of
      energy homeostasis. AMPK is also modulated in response to inflammatory signals,
      although its functions in inflamed tissue are obscure. We investigated the role
      of activated AMPK in the retinal neural damage and visual function impairment
      caused by inflammation. For this purpose, we used a mouse model of
      lipopolysaccharide-induced inflammation in the retina, and examined the effects
      of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR).
      During inflammation, activated AMPK in the neural retina was decreased, but AICAR
      treatment prevented this change. Moreover, the electroretinogram (ERG) a-wave
      response, representing photoreceptor function, showed visual dysfunction in this
      model that was prevented by AICAR. Consistently, the model showed shortened
      photoreceptor outer segments (OSs) with reduced levels of rhodopsin, a visual
      pigment concentrated in the OSs, in a post-transcriptional manner, and these
      effects were also prevented by AICAR. In parallel, the level of activated NF
      kappaB increased in the retina during inflammation, and this increase was
      suppressed by AICAR. Treatment with an NF-kappaB inhibitor,
      dehydroxymethylepoxyquinomicin (DHMEQ) preserved the rhodopsin level during
      inflammation, suppressing NF-kappaB. These findings indicated that AMPK
      activation by AICAR and subsequent NF-kappaB inhibition had a protective effect
      on visual function, and that AMPK activation played a neuroprotective role during
      retinal inflammation. 

PMID- 25048040
TI  - Neuropsychological outcome after carbon monoxide exposure following a storm: a
      case-control study.
AB  - BACKGROUND: The cognitive consequences of carbon monoxide (CO) poisoning are well
      described. However, most studies have been carried out without an ad-hoc group of
      control subjects. The main aim of this study was to evaluate cognitive and
      psychiatric outcome after CO exposure during the storm Klaus in the South West of
      France (January 2009) in a homogeneous group of patients compared to a group of
      1:1 paired controls. METHODS: Patients and controls were asked to fill out
      questionnaires about quality of life and cognitive complaints. They then
      underwent a cognitive assessment derived from the Carbon Monoxide
      Neuropsychological Screening Battery. Psychiatric assessment was performed using
      subtests of the Mini International Neuropsychiatric Interview. RESULTS: 38
      patients and 38 paired controls were included (mean age 38.8 years) and evaluated
      51 days after the poisoning. No difference was found between groups on the
      cognitive complaint questionnaire but patients had a lower quality of life than
      controls. Patients showed significantly lower cognitive performance than controls
      on processing speed, mental flexibility, inhibition and working and verbal
      episodic memories. Patients were more depressed than controls, and suffered more
      from post-traumatic stress disorder. CONCLUSIONS: We report the first study
      investigating cognitive and psychiatric outcome in consecutive patients after CO
      poisoning during a natural disaster, using a group comparison method. CO
      poisoning during storms needs to be dealt with adequately and clinicians should
      be aware of its possible consequences.

PMID- 25048041
TI  - Collecting real-time data from substance users raises unique legal and ethical
      issues: reply to Kuntsche & Labhart.

PMID- 25048042
TI  - A new Gold Rush? The future in ECG research.

PMID- 25048043
TI  - Trabectedin in soft tissue sarcomas.
AB  - Trabectedin (Yondelis(r); PharmaMar, Madrid, Spain), a synthetic anticancer agent
      originally isolated from the Caribbean tunicate, Ecteinascidia turbinata, is
      currently approved in more than 70 countries worldwide for the treatment of soft
      tissue sarcoma (STS). Trabectedin is an isoquinoline alkylating agent that,
      unlike other alkylating agents, binds in the DNA minor groove to initiate
      cytotoxic activity. Other multitarget mechanisms of action of trabectedin include
      important effects within the tumor microenvironment; in particular, trabectedin
      possesses indirect anti-inflammatory and anti-angiogenic activity via tumor
      associated macrophages and high-specificity modulation of various transcription
      factors. The clinical efficacy of trabectedin, administered intravenously over 24
      h every 3 weeks, has been demonstrated in several studies in patients with STS.
      In the Phase II STS-201 trial, 270 patients with liposarcoma or leiomyosarcoma
      were randomized to receive trabectedin 1.5 mg/m(2) given as a 24-h intravenous
      (iv.) infusion every 3 weeks or as a weekly regimen (0.58 mg/m(2); 3-h iv.
      infusion for three consecutive weeks in a 4-week cycle). There was a
      statistically significant and clinically relevant 27% reduction in the risk of
      disease progression (primary end point) with trabectedin given as a 24-h infusion
      q3w (p = 0.0302) with an overall survival rate at 12 months of 60%. Trabectedin
      was generally well tolerated; the most frequently reported severe adverse events
      were neutropenia (47% of patients) and elevated transaminases (47%). Overall, the
      majority of adverse events were mild to moderate and, despite a long duration of
      exposure to trabectedin in some patients, no cumulative toxicities were
      experienced.

PMID- 25048044
TI  - Going further in the knowledge of Yondelis(r); what's new in daily clinical
      practice?
AB  - The approval of trabectedin in Europe in 2007 for the treatment of advanced soft
      tissue sarcoma (STS) was based on four Phase II trials. The extensive clinical
      trials program currently underway with trabectedin indicates clearly the extent
      to which this novel agent remains a topic of scientific and clinical interest in
      the treatment of advanced STS. Results of several retrospective studies examining
      outcomes of patients treated beyond clinical trials and under everyday practice
      conditions, including compassionate use programs, were disclosed in 2013. These
      analyses complement the knowledge about trabectedin gained from previous and
      ongoing clinical studies. Collectively, the results confirm the activity of
      trabectedin in inoperable/metastatic STS and extend current knowledge about
      several aspects of its profile, highlighting in particular improved outcomes when
      trabectedin is used in earlier lines of therapy and when treatment is maintained
      in the absence of disease progression. Evidence that the safety profile of
      trabectedin does not differ materially between elderly (>=65 years) and younger
      patients suggests no need to discriminate on the basis of age; elderly patients
      who are sufficiently fit to receive chemotherapy and considered by their
      physicians as unsuited to receive doxorubicin/ifosfamide can be treated with
      trabectedin in the same manner as younger patients.

PMID- 25048045
TI  - Soft tissue sarcomas, a look into the future: different treatments for different
      subtypes.
AB  - Soft tissue sarcomas (STS) are a heterogeneous group of rare malignancies
      frequently studied and treated as if they were one and the same disease. Evidence
      is emerging that distinct histopathological differences between the subtypes can
      significantly impact on optimal management of patients with STS. For the majority
      of patients with localized disease, surgery is the treatment of choice, sometimes
      combined with radiotherapy. For patients with advanced/refractory disease, there
      are a number of options. The first option is to consider cytotoxic chemotherapy
      with doxorubicin +/- ifosfamide to reduce tumor size and make the tumor more
      amenable to surgery. If this is not possible, treatment should be aimed at
      reducing symptoms, improving patients' wellbeing and prolonging life. In this
      regard, understanding of the different biologies and sensitivities of the various
      histological subtypes of STS continues to expand, and an increasing number of
      targeted therapies are becoming available. Examples of more specific treatment
      options include taxanes in angiosarcoma, and trabectedin in leiomyosarcoma,
      liposarcoma and undifferentiated pleomorphic sarcoma. Although much remains to be
      learned about these rare malignancies, it is anticipated that small steps taken
      in recent years will lead to bigger leaps forward in future. 

PMID- 25048046
TI  - Going further in the knowledge of Yondelis(r); what's new in clinical trials?
AB  - Trabectedin is indicated for the treatment of advanced soft tissue sarcoma (STS)
      after failure of standard therapy with anthracyclines and ifosfamide, or as first
      line therapy for patients who are unsuited to receive these agents. Since
      trabectedin first became available for clinical investigation in 1995, numerous
      retrospective analyses and Phase II studies have documented its activity and
      provided useful insights into its unique clinical profile. An extensive research
      program of randomized studies was subsequently undertaken to identify methods of
      optimizing the use of trabectedin in clinical practice. Some main areas of
      interest involved its use in the first-line setting, its use in combination
      regimens and its activity in specific sarcoma subtypes. In this article, clinical
      trial results are reviewed with the aim of continually refining trabectedin's
      place in the therapy of advanced STS.

PMID- 25048047
TI  - Effect of inter-cycle interval on oocyte production in humans in the presence of
      the weak androgen DHEA and follicle stimulating hormone: a case-control study.
AB  - BACKGROUND: In various animal models androgens have been demonstrated to enhance
      follicle stimulating hormone (FSH) activity on granulosa cells during small
      growing follicle stages. To assess whether similar synergism may also exist in
      humans we investigated women on androgen (dehydroepiandrosterone, DHEA)
      supplementation with varying concomitant FSH exposure. METHODS: In a case
      controlled cohort study we determine if time interval between IVF cycles of IVF
      treatment with FSH had an effect on ovarian response to ovulation induction in
      women supplemented with DHEA. Among 85 women with known low functional ovarian
      reserve (LFOR), supplemented with DHEA, and undergoing at least 3 consecutive IVF
      cycles, 68 demonstrated short (<120 days) intervals between repeated cycles
      (Group 1) and were, therefore, considered to have consistent FSH exposure. In
      contrast 17 women (Group 2) demonstrated long (>=120 days) intervals between
      repeated cycles and, therefore, were considered to demonstrate inconsistent FSH
      exposure. Trends in oocyte yields were compared between these groups, utilizing
      mixed model repeated measures ANOVA, adjusted for initial age and FSH dose.
      RESULTS: Only women in Group I demonstrated a linear increase in oocyte yields
      across their three cycles of treatments (F=7.92; df 1, 68.6; p=0.017). Moreover,
      the analysis revealed a significant interaction between the two patient groups
      and cycle number for retrieved oocytes (F=6.32, df=2, 85.9, p=0.003).
      CONCLUSIONS: This study offers preliminary confirmatory evidence that repeated
      short interval exposure to androgens in combination with FSH improves human FOR.
      A higher level of evidence will require prospectively randomized studies.

PMID- 25048048
TI  - Comparison of lower lip hypoesthesia between hybrid fixation and conventional
      fixation following sagittal split ramus osteotomy.
AB  - PURPOSE: The purpose of this study was to compare the recovery period of lower
      lip hypoesthesia between hybrid fixation and conventional fixation using
      absorbable plates and screw systems following sagittal split ramus osteotomy
      (SSRO). SUBJECTS AND METHODS: The subjects were 66 patients (132 sides) who
      underwent bilateral SSRO setback surgery. They were divided into a hybrid
      fixation group (66 sides, 1 u-HA/PLLA plate and 4 mono-cortical screws and a bi
      cortical screw in each side) and a conventional fixation group (66 sides, 1 u
      HA/PLLA plate and 4 mono-cortical screws in each side). Trigeminal nerve
      hypoesthesia at the region of the lower lip was assessed bilaterally by the
      trigeminal somatosensory-evoked potential (TSEP) method. RESULTS: The mean
      measurable periods were 8.1 +/- 10.4 weeks in the hybrid fixation group, 5.1 +/-
      11.5 weeks in the conventional group with no significant difference. However, the
      maximum in the hybrid fixation group was 27 sides at 4 weeks postoperative and in
      the conventional fixation group was 37 sides at 1 week postoperative, and there
      was significant difference in the distribution of the measurable period (P <
      0.0001). CONCLUSION: This study suggested that additional bi-cortical screws
      could affect the recovery of lower lip hypoesthesia after SSRO with bent
      absorbable plate fixation.

PMID- 25048049
TI  - Progressive midfacial bone erosion and necrosis: case report and differential
      diagnosis.
AB  - A 31-year-old woman presented with a large oro-nasal communication (ONC), loss of
      vomer and significant nasal cartilage and nose deformity. Physical examination of
      the patient revealed a typical midline destructive lesion (MDL) with nasal septum
      and hard/soft palate perforation with a friable granular surface and a large
      amount of necrotic tissues. Medical history was unremarkable and the patient
      denied previous local trauma, including surgical procedures or drug assumption.
      Pathological examination revealed the presence of necrosis and chronic
      inflammation. MDLs have numerous etiologies. Signs and symptoms of MDLs can be
      similar and an accurate diagnosis may be elusive. We hereby present detailed
      clinicopathological findings.

PMID- 25048050
TI  - Rat subthalamic nucleus and zona incerta share extensively overlapped
      representations of cortical functional territories.
AB  - The subthalamic nucleus (STN) and the zona incerta (ZI) are two major structures
      of the subthalamus. The STN has strong connections between the basal ganglia and
      related nuclei. The ZI has strong connections between brainstem reticular nuclei,
      sensory nuclei, and nonspecific thalamic nuclei. Both the STN and ZI receive
      heavy projections from a subgroup of layer V neurons in the cerebral cortex. The
      major goal of this study was to investigate the following two questions about the
      cortico-subthalamic projections using the lentivirus anterograde tracing method
      in the rat: 1) whether cortical projections to the STN and ZI have independent
      functional organizations or a global organization encompassing the entire
      subthalamus as a whole; and 2) how the cortical functional zones are represented
      in the subthalamus. This study revealed that the subthalamus receives heavy
      projections from the motor and sensory cortices, that the cortico-subthalamic
      projections have a large-scale functional organization that encompasses both the
      STN and two subdivisions of the ZI, and that the group of cortical axons that
      originate from a particular area of the cortex sequentially innervate and form
      separate terminal fields in the STN and ZI. The terminal zones formed by
      different cortical functional areas have highly overlapped and fuzzy borders, as
      do the somatotopic representations of the sensorimotor cortex in the subthalamus.
      The present study suggests that the layer V neurons in the wide areas of the
      sensorimotor cortex simultaneously control STN and ZI neurons. Together with
      other known afferent and efferent connections, possible new functionality of the
      STN and ZI is discussed.

PMID- 25048052
TI  - Perspectives of carers on medication management in dementia: lessons from
      collaboratively developing a research proposal.
AB  - BACKGROUND: The need for carers to manage medication-related problems for people
      with dementia living in the community raises dilemmas, which can be identified by
      carers and people with dementia as key issues for developing carer-relevant
      research projects. A research planning Public Patient Involvement (PPI) workshop
      using adapted focus group methodology was held at the Alzheimer's Society's
      national office, involving carers of people with dementia who were current
      members of the Alzheimer's Society Research Network (ASRN) in dialogue with
      health professionals aimed to identify key issues in relation to medication
      management in dementia from the carer viewpoint. The group was facilitated by a
      specialist mental health pharmacist, using a topic guide developed systematically
      with carers, health professionals and researchers. Audio-recordings and field
      notes were made at the time and were transcribed and analysed thematically. The
      participants included nine carers in addition to academics, clinicians, and staff
      from DeNDRoN (Dementias and Neurodegenerative Diseases Research Network) and the
      Alzheimer's Society. FINDINGS: Significant themes, for carers, which emerged from
      the workshop were related to: (1) medication usage and administration
      practicalities, (2) communication barriers and facilitators, (3) bearing and
      sharing responsibility and (4) weighing up medication risks and benefits. These
      can form the basis for more in-depth qualitative research involving a broader,
      more diverse sample. DISCUSSION: The supported discussion enabled carer voices
      and perspectives to be expressed and to be linked to the process of identifying
      problems in medications management as directly experienced by carers. This was
      used to inform an agenda for research proposals which would be meaningful for
      carers and people with dementia.

PMID- 25048051
TI  - Immunohistochemical profile of oral mucosal and head and neck cutaneous melanoma.
AB  - BACKGROUND: In addition to ultraviolet radiation exposure, various molecular
      markers may differ between oral mucosal and cutaneous head and neck melanomas and
      lead to variations in their biologic behavior and prognosis. The aim of this
      study was to compare four such markers, namely microphthalmia transcription
      factor (MITF), P75, P53, and Ki-67 in malignant melanomas originating from the
      oral cavity and head and neck skin. METHODS: A total of 19 oral mucosal and 23
      head and neck cutaneous melanomas were subjected to immunohistochemical analysis
      using antibodies against MITF, P75, P53, and Ki-67. Statistical comparison of
      data was performed by t-test and chi-square analysis (P < 0.05). RESULTS:
      Significant differences in MITF (P = 0.016) and Ki-67 (P = 0.002) were observed
      between oral mucosal and cutaneous melanomas. P75 (P = 0.80) and P53 (P = 0.76)
      did not differ significantly, between these locations. CONCLUSIONS: According to
      the results obtained in this study, the biological properties of cutaneous and
      mucosal melanoma differ, especially regarding MITF and Ki-67.

PMID- 25048053
TI  - Lifetime medical costs of knee osteoarthritis management in the United States:
      impact of extending indications for total knee arthroplasty.
AB  - OBJECTIVE: The impact of increasing utilization of total knee arthroplasty (TKA)
      on lifetime costs in persons with knee osteoarthritis (OA) is understudied.
      METHODS: We used the Osteoarthritis Policy Model to estimate total lifetime costs
      and TKA utilization under a range of TKA eligibility criteria among US persons
      with symptomatic knee OA. Current TKA utilization was estimated from the
      Multicenter Osteoarthritis Study and calibrated to Health Care Cost and
      Utilization Project data. OA treatment efficacy and toxicity were drawn from
      published literature. Costs in 2013 dollars were derived from Medicare
      reimbursement schedules and Red Book Online. Time costs were derived from
      published literature and the US Bureau of Labor Statistics. RESULTS: Estimated
      average discounted (3% per year) lifetime costs for persons diagnosed with knee
      OA were $140,300. Direct medical costs were $129,600, with $12,400 (10%)
      attributable to knee OA over 28 years. OA patients spent a mean +/- SD of 13 +/-
      10 years waiting for TKA after failing nonsurgical regimens. Under current TKA
      eligibility criteria, 54% of knee OA patients underwent TKA over their lifetimes.
      Estimated OA-related discounted lifetime direct medical costs ranged from $12,400
      (54% TKA uptake) when TKA eligibility was limited to Kellgren/Lawrence grades 3
      or 4 to $16,000 (70% TKA uptake) when eligibility was expanded to include
      symptomatic OA with a lesser degree of structural damage. CONCLUSION: Because of
      low efficacy of nonsurgical regimens, knee OA treatment-attributable costs are
      low, representing a small portion of all costs for OA patients. Expanding TKA
      eligibility increases OA-related costs substantially for the population,
      underscoring the need for more effective nonoperative therapies.

PMID- 25048054
TI  - Inferring mechanisms of copy number change from haplotype structures at the human
      DEFA1A3 locus.
AB  - BACKGROUND: The determination of structural haplotypes at copy number variable
      regions can indicate the mechanisms responsible for changes in copy number, as
      well as explain the relationship between gene copy number and expression.
      However, obtaining spatial information at regions displaying extensive copy
      number variation, such as the DEFA1A3 locus, is complex, because of the
      difficulty in the phasing and assembly of these regions. The DEFA1A3 locus is
      intriguing in that it falls within a region of high linkage disequilibrium,
      despite its high variability in copy number (n = 3-16); hence, the mechanisms
      responsible for changes in copy number at this locus are unclear. RESULTS: In
      this study, a region flanking the DEFA1A3 locus was sequenced across 120
      independent haplotypes with European ancestry, identifying five common classes of
      DEFA1A3 haplotype. Assigning DEFA1A3 class to haplotypes within the 1000 Genomes
      project highlights a significant difference in DEFA1A3 class frequencies between
      populations with different ancestry. The features of each DEFA1A3 class, for
      example, the associated DEFA1A3 copy numbers, were initially assessed in a
      European cohort (n = 599) and replicated in the 1000 Genomes samples, showing
      within-class similarity, but between-class and between-population differences in
      the features of the DEFA1A3 locus. Emulsion haplotype fusion-PCR was used to
      generate 61 structural haplotypes at the DEFA1A3 locus, showing a high within
      class similarity in structure. CONCLUSIONS: Structural haplotypes across the
      DEFA1A3 locus indicate that intra-allelic rearrangement is the predominant
      mechanism responsible for changes in DEFA1A3 copy number, explaining the
      conservation of linkage disequilibrium across the locus. The identification of
      common structural haplotypes at the DEFA1A3 locus could aid studies into how
      DEFA1A3 copy number influences expression, which is currently unclear.

PMID- 25048056
TI  - Epididymal-testicular fusion anomalies in cryptorchidism are associated with
      proximal location of the undescended testis and with a widely patent processus
      vaginalis.
AB  - Past studies documented the presence of epididymal/testicular fusion anomalies
      and persistence of a patent processus vaginalis in a small case-series of
      cryptorchid and/or hydrocele patients. The primary aim of this study was to
      determine the prevalence of the epididymal/testicular anomalies in a series of
      more than 1000 cryptorchid patients compared with controls. Secondary aims were:
      (i) to investigate the association between the cryptorchidism and the patency of
      p. vaginalis; and (ii) to correlate the epididymal/testicular fusion anomalies
      with the position of the testis and with the patency of the p. vaginalis. The
      clinical and surgical data of 1002 cryptorchid patients and 230 controls were
      retrospectively retrieved and analysed. Epididymal/testicular fusion anomalies
      were classified as: (i) normal anatomy; (ii) minor anomalies; and (iii) major
      anomalies. Statistical analysis was performed using the Student's t-test and Chi
      square tests. The prevalence of the epididymal/testicular fusion anomalies was
      higher in the cryptorchid group compared with that of the control group (minor
      and major anomalies in cryptorchids vs. controls, respectively: 42.2 vs. 5.6% and
      9.3 vs. 1.6%, P < 0.0001). Moreover, we documented a correlation of these
      anomalies with a more proximal localization of the testis (minor and major
      anomalies in proximal vs. distal location of the testis, respectively: 62.5 vs.
      34.8% and 19.1 vs. 6.3%, P < 0.0001) and with the persistence of a widely patent
      p. vaginalis (minor and major anomalies in widely patent p. vaginalis vs. narrow
      duct, respectively: 51.7 vs. 42.2 and 11.9% vs. 7.8%, P < 0.001). In conclusion,
      the epididymal/testicular fusion anomalies were strongly associated with
      cryptorchidism and the persistence of a widely patent peritoneal vaginal duct.
      Although it remains unclear whether these anomalies cause non-descent of the
      testis or, conversely, result from the cryptorchidism or from the persistence of
      a widely patent duct, our data re-enforce this association.

PMID- 25048057
TI  - Photodiagnosis and Photodynamic Therapy: the birth of a Journal.

PMID- 25048058
TI  - Photodynamic therapy: from the beginning.
AB  - Photodynamic therapy relates to the use of drugs + light for treatment of
      neoplasia, macular degeneration and atherosclerotic plaque. This field has a long
      history with recent improvements in drug development and light sources promoting
      clinical approaches. This summary describes recent progress along with an
      indication of current lines of research. 

PMID- 25048059
TI  - Photodiagnosis and fluorescence imaging in clinical practice.
AB  - For cancer diagnosis clinicians rely upon histo pathological preparations in
      their broadest sense and the characteristic microscopic features which represent
      malignant changes. Standard method of in-vivo sampling (biopsy) uses white light
      indicating abnormal tissue. The manner in which light interacts with a specific
      tissue type is dictated by the wavelength dependent scattering and absorbtion
      properties. In the UV and visible part of the spectrum the tissue optical
      properties are dominated by the endogenous chromophores which is different for
      normal/abnormal tissue. It follows that abnormal tissue, absorbs light and
      fluoresces differently to normal tissue at specific light wavelengths.
      Autofluorescence takes advantage of this principle. Enhanced fluorescence employs
      exogenous markers to produce better definition. Fluorescence imaging has become
      an important diagnostic tool to highlight cancer at an early stage of development
      and/or to guide biopsy from representative samples. 

PMID- 25048060
TI  - Autofluorescence (safe) bronchoscopy and p21/ki-67 immunostaining related to
      carcinogenesis.
AB  - Archival biopsy materials from 20 randomly selected asymptomatic volunteers from
      the Czech uranium miners (CZ UM) risk group (n=98) were examined for p21 and ki
      67 immunostatning. There were 16 areas with normal respiratory epithelium and 22
      areas with bronchial intra-epithelial neoplasia (IEN). Normal and IEN areas were
      identified by autofluorescence (System Autofluorescence Endoscopy, SAFE-1000) and
      monitored during 1998-2002. The majority of specimens from areas with normal
      autofluorescence intensity with ciliated columnar bronchial epithelium showed
      strong predominantly cytoplasmic p21 positivity. The SAFE monitoring divided
      areas of decreased autofluorescence intensity with early stage IEN lesions into
      two groups. Persistent lesions (P)-showing a spectrum of p21 cytoplasmic staining
      ranging from negative or isolated negativity to weak or moderate positivity
      combined with higher proliferative capacity proved by ki-67 nuclear staining.
      Disappearing lesions (D)-showing strong cytoplasmic p21 positivity and negative
      ki-67 staining. The IEN lesions were classified into three groups based on p21/ki
      67 immunostaining: proliferative lesions at risk (R) with low or without p21
      plasma immunostaining combined with high ki-67 nuclear reactivity; ambiguous
      lesions (A) including cases combining strong p21 cytoplasmic positivity with high
      ki-67 nuclear reactivity or p21 cytoplasmic negativity with ki-67 negativity
      staining patterns; the quiescent lesion group (Q) was characterized by strong p21
      cytoplasmic positivity and negative ki-67 immunostaining. 

PMID- 25048061
TI  - Fluorescent diagnosis of urinary bladder cancer-a comparison of two diagnostic
      modalities.
AB  - White light cystoscopy (WLC) is considered to be a standard examination for
      localisation and surveillance of transitional cell cancer of urinary bladder.
      However, in patients who have undergone transurethral resection of bladder tumour
      (TUR-BT) sensitivity of this method is too low for early detection of cancer
      recurrence. In order to improve this unsatisfactory situation new diagnostic
      procedures are still under investigation. Fluorescent diagnosis is a modern
      diagnostic option based on the detection of distinctive fluorescence of normal
      and pathological tissue. Currently two techniques are in clinical use:
      autofluorescent diagnosis, also termed laser-induced fluorescence (LIF) and
      photodynamic diagnosis (PDD). In this study we have analysed sensitivity and
      specificity of the fluorescent diagnosis to validate the best mode of bladder
      cancer diagnosis. A total of 281 patients, after electroresection of bladder
      tumour due to transitional cell carcinoma, without any signs of tumour recurrence
      in white-light cystoscopy, were divided in two groups: 52 patients underwent PDD
      and in 229 patients autofluorescent diagnosis was performed. Bladder washings and
      excisions from suspicious red fluorescent spots were taken for histopathological
      and cytological analyses. Sensitivity and specificity of PDD equalled to 90.91
      and 66.60%, respectively. In case of autofluorescence diagnosis these values
      amounted to: 97.83 and 70.07%, respectively. The overall sensitivity and
      specificity of fluorescent examination equalled to 96.49 and 69.46%,
      respectively. CONCLUSION: Autofluorescence diagnosis (LIF) of pathological
      lesions within urinary bladder has been proven to be more sensitive than PDD as
      evaluated by a non-parametrical test for structure indicators comparison (LIF
      versus PDD, P=0.0056).

PMID- 25048062
TI  - Photosensitizers in clinical PDT.
AB  - Photosensitizers in photodynamic therapy allow for the transfer and translation
      of light energy into a type II chemical reaction. In clinical practice,
      photosensitizers arise from three families-porphyrins, chlorophylls, and dyes.
      All clinically successful photosensitizers have the ability to a greater or
      lesser degree, to target specific tissues or their vasculature to achieve
      ablation. Each photosensitizer needs to reliably activate at a high enough light
      wavelength useful for therapy. Their ability to fluoresce and visualize the
      lesion is a bonus. Photosensitizers developed from each family have unique
      properties that have so far been minimally clinically exploited. This review
      looks at the potential benefits and consequences of each major photosensitizer
      that has been tried in a clinical setting. 

PMID- 25048063
TI  - Lasers and light sources for PDT: past, present and future.
AB  - The more recent use of Photodynamic therapy in Oncology dates to the early
      1970's, when Dr. Thomas J. Dougherty, began his investigations into the
      mechanisms and clinical uses hematoporphyrin derivative (HpD). Since then the
      therapy has found its way through the regulatory process in numerous countries
      throughout the world. In many of these locales as it was in the United States,
      this was the first drug device approval, for oncology, that had been undertaken
      and ultimately approved, by the regulatory agencies in the respective countries.
      Throughout this time changes occurred in the formulation of HpD as well as the
      development of other photosensitizers. The more difficult aspect, however, of
      this modality has been the availability of reliable, affordable and appropriate
      devices for the production and delivery of light to the targeted areas. In the
      last 10 years, however, there has been a slow yet improving landscape in the
      development of devices for PDT that ultimately will provide the impetus for
      greater acceptance of PDT in the medical community. 

PMID- 25048064
TI  - Photodynamic therapy (PDT) of lung cancer: experience of the Tokyo Medical
      University.
AB  - Endoscopic low (Photodynamic therapy (PDT)) or high (vaporization) power laser
      treatment has been recognized as a lung-sparing local therapeutic modality that
      can achieve remarkable responses. This paper reviews the experience of our
      institution since 1978 in the treatment of lung cancer using laser. Endoscopic
      ablation of tracheobronchial malignancies is mainly intended to reduce
      respiratory distress and improve quality of life. Effective results were obtained
      in 143 (81%) of the 177 lesions. PDT is extremely attractive and has been used
      for the various purposes. In the curative PDT for centrally located early stage
      lung cancer, complete response (CR) rate was achieved in 86.4% (165 out of 191
      lesions). Overall 5-year survival rate was 57.6% and the lung cancer specific 5
      year survival rate was 92.5%. With regard to palliative PDT to opening obstructed
      bronchi in advanced cases, more than 50% opening of the obstruction was
      accomplished in 75%. Preoperative PDT was performed in 32 patients with lung
      cancer for the purpose of either reducing the extent of resection or increasing
      operability. The initial purpose of PDT was achieved in 27 of 32 patients
      treated. Conversion to an operable condition was achieved in 4 of 5 originally
      inoperable cases. In 23 of 27 patients who were originally candidates for
      pneumonectomy, it became possible to reduce the extent of resection to lobectomy
      or sleeve lobectomy. PDT could be used to treat peripheral tiny lung cancers
      safely and without unacceptable effects on surrounding tissue. The authors
      believe that PDT has a great potential and will achieve further development in
      the future. 

PMID- 25048065
TI  - Photodynamic therapy enhanced by hyperbaric oxygenation in palliation of
      malignant pleural mesothelioma: clinical experience.
AB  - INTRODUCTION: Surgical debulking followed by radiotherapy/chemotherapy are the
      standards in the palliative treatment schedule of malignant pleural mesothelioma.
      The aim of this study was to evaluate the additional effect of intraoperative
      photodynamic therapy (PDT) under hyperbaric oxygenation (HBO) if compared to
      decortication alone. PATIENTS AND METHODS: From January 1993 to August 2003,
      decortication was done in 34 patients (28 males, 6 females; mean age: 65 years)
      suffering from advanced malignant pleural mesothelioma. Twenty-two patients
      received additional intraoperative PDT under HBO. The surgery and PDT/HBO was
      done 48h after photosensitization with a polyhematoporphyrin, 2mg/kg BW using a
      diode laser delivering red light at 630nm through a microlens. The light dose was
      calculated for 300J at a distance of 1cm from the tumour surface. RESULTS: At 6
      month follow-up the Karnofsky performance status showed no significant difference
      (P>=0.05) between both groups. CT scans documented focal regrowth of the tumour
      after 6 months in 10/12 cases of the non-PDT group. However, in the PDT group
      tumour regrowth was detected in only 9/22 cases at 6-month follow-up. Survival
      analysis showed a significant advantage for the group with PDT (log-rank test:
      P=0.0179). CONCLUSION: Although the study includes only a small number of
      patients, it indicates that additional PDT/HBO represents a safe and technically
      feasible approach in the palliative setting of advanced malignant mesothelioma of
      the pleura.

PMID- 25048066
TI  - Photodynamic therapy in the esophagus.
AB  - Photodynamic therapy (PDT) involves in situ photo-activation of photosensitizers
      by light at appropriate wavelength, generating highly active singlet oxygen and
      free radicals. For esophageal mucosal dysplasia such as high-grade dysplasia or
      intramucosal cancer, curative endoluminal therapy including PDT is now a reality.
      We review the role of PDT in the esophagus for the past two decades. The light
      for PDT can be delivered endoluminally freehand by cylindrical diffusers, via
      inflatable balloon stabilizers or microlens fibers. Porfimer sodium
      (Photofrin((r))) is the only approved photosensitizer for PDT in the esophagus in
      North America, Europe and Japan. In addition, 5-aminolaevulinic acid (ALA), m
      tetra(hydroxyphenyl)chlorin (m-THPC) and benzoporphyrin derivative monoacid ring
      A (BPD-MA) are other photosensitizers are being evaluated. More randomized
      clinical trials with long term follow up data are needed to further establish the
      role of PDT and other endoluminal ablative therapies either on their own or in
      combination to demonstrate survival benefits, quality of life advantages and cost
      effectiveness. Changes in light delivery, timing, dosimetry and new endoscopic
      devices are needed to possibly improve all aspects of effectiveness. PDT was used
      mainly for palliation of advanced obstructing cancer of the esophagus at the
      gastrointestinal junction. More recently, because of the rising detection of the
      high-grade dysplasia in Barrett's esophagus, a curative role of PDT in being
      realized. 

PMID- 25048067
TI  - The light solution for Barrett's oesophagus Photodiagnosis and photodynamic
      therapy for columnar-lined oesophagus.
AB  - BACKGROUND: Barrett's oesophagus is the columnar-lined metaplasia that occurs in
      response to severe gastro-oesophageal reflux and accounts for the dramatic rise
      in adenocarcinoma at the gastro-oesophageal junction. DIAGNOSTIC METHODS:
      Endoscopic recognition and pathological diagnosis of the condition is fraught
      with erroneous interpretation of the pre-malignant degeneration of dysplasia.
      Screening and surveillance programmes have yet to impact on the disease.
      Photodiagnosis by spectroscopy and imaging is under intense investigation. The
      methods can be divided into two groups of morphological (elastic scattering,
      optical coherence tomography) and molecular and biochemical (Raman and
      fluorescence). The major diagnostic problem remains the differentiation between
      inflammation and dysplasia. Raman spectroscopy does offer molecular-specific
      diagnosis and fibre-optic probes are being developed. The future appears to be
      multi-modal imaging combined with spectroscopy. RESULTS: Photodynamic therapy is
      a realistic option for the eradication of dysplastic Barrett's oesophagus. A
      recently reported randomised trial has demonstrated a significant improvement in
      the eradication of dysplasia and prevention of oesophageal cancer. CONCLUSIONS:
      Optical diagnosis and optical eradication have a bright future for the management
      of Barrett's oesophagus.

PMID- 25048068
TI  - Photodynamic therapy in cholangiocarcinoma: an overview.
AB  - Cholangiocarcinoma is a challenge to manage; mortality rate is nearly as high as
      the incidence. Unless curative resection is performed, these tumours are rapidly
      fatal because they respond poorly to current therapies. Symptoms occur late in
      cholangiocarcinoma and curative resection can be performed in less than half of
      the patients. In non-resectable disease, endoprostheses insertion can relieve
      jaundice and improve quality of life, provided that tumour extension does not
      lead to diffuse intrahepatic stenoses of ductal system. However, tumour growth
      cannot be influenced and therefore, prognosis remains dismal. Despite the fact,
      that radiotherapy and chemotherapy could reduce tumour volume and growth, no
      survival advantage has yet been shown. Photodynamic therapy has been evaluated as
      an new additional, palliative option. A randomised trial comparing photodynamic
      therapy plus endoprostheses insertion versus endoprostheses insertion alone,
      indicates a considerably benefit on survival time, cholestasis and quality of
      life in large, advanced cholangiocarcinoma. Furthermore, few specific side
      effects occurred. Since photodynamic therapy is the first approach leading to an
      improvement of prognosis, it should be offered to patients with non-resectable
      cholangiocarcinoma. 

PMID- 25048069
TI  - Photodynamic assisted surgical resection and treatment of malignant brain tumours
      technique, technology and clinical application.
AB  - Malignant brain tumours have a dismal prognosis with current state of the art
      technology. The main reasons for this lost battle in the battlefield of cancer
      are tumour cell invisibility to the surgical microscope and brain invasion.
      However, the vast majority of these tumours relapse locally making local radical
      removal the main strategy in their successful eradication. PDD and PDT combined
      with new technology stands a very good chance of achieving this goal by
      maximising tumour resection (PDD) and selective tumour kill (PDT). The aim of
      this paper is to explain how this is done at Ninewells Hospital and Medical
      School, Dundee, Scotland. The technique and technology described in this paper,
      provide a means of diffusing the light to the periphery of the tumour cavity with
      subsequent therapeutic sessions and treatment dose escalation at the bedside,
      saving time and resources. 

PMID- 25048070
TI  - Photodynamic therapy for tracheal thyroid metastasis.
AB  - We report the case of a patient with recurrence of follicular carcinoma of the
      thyroid 8 years after surgical resection followed by external beam radiotherapy
      and radio-iodine treatment. The patient was treated by endoscopic photodynamic
      therapy (PDT) with complete endoscopic response after 12 months with good symptom
      relief. 

PMID- 25048071
TI  - Renal sparing treatment of upper tract malignant urothelial tumours using
      photodynamic therapy (PDT)-three case reports.
AB  - Urothelial cancers of the upper urinary tract are usually treated by excision of
      the kidney, ureter and cuff of the bladder on the affected side. These three
      cases demonstrate the feasibility, safety and efficacy of photodynamic therapy as
      a renal sparing procedure for urothelial tumours. 

PMID- 25048072
TI  - Post activation potentiation can be induced without impairing tendon stiffness.
AB  - PURPOSE: This study aimed to investigate conditioning effects from a single 6-s
      plantar flexion maximal voluntary isometric contraction (MVIC) on Achilles tendon
      stiffness (ATS) and twitch properties of the triceps surae in athletes. METHODS:
      Peak twitch (PT), rate of torque development (RTD), rising time (RT10-90%) and
      half relaxation time (HRT) were measured from supramaximal twitches evoked in the
      plantar flexors of 10 highly trained athletes. Twitches were evoked before and at
      seven occasions during 10 min of recovery after a 6-s MVIC. In a second session,
      but at identical post-conditioning time points, ATS was measured at 30 and 50% of
      MVIC (ATS30% and ATS50%) using an ultrasonography-based method. RESULTS: The
      magnitude and duration of the conditioning MVIC on muscle contractile properties
      were in accordance with previous literature on post activation potentiation
      (PAP), i.e., high potentiation immediately after MVIC, with significant PAP for
      up to 3 min after the MVIC. While PT and RTD were significantly enhanced (by 60.6
      +/- 19.3 and 90.1 +/- 22.5%, respectively) and RT10-90% and HRT were reduced (by
      10.1 +/- 7.7 and 18.7 +/- 5.6%, respectively) after conditioning, ATS remained
      unaffected. CONCLUSIONS: Previous studies have suggested that changes in
      stiffness after conditioning may interfere with the enhancements in twitch
      contractile properties. The present study, however, provided some evidence that
      twitch enhancements after a standard PAP can be induced without changes in ATS.
      This result may suggest that athletes can use this protocol to enhance muscle
      contractile properties without performance deficits due to changes in ATS.

PMID- 25048073
TI  - Effect of countermovement on power-force-velocity profile.
AB  - PURPOSE: To study the effect of a countermovement on the lower limb force
      velocity (F-v) mechanical profile and to experimentally test the influence of F-v
      mechanical profile on countermovement jump (CMJ) performance, independently from
      the effect of maximal power output (P max). METHODS: Fifty-four high-level
      sprinters and jumpers performed vertical maximal CMJ and squat jump (SJ) against
      five to eight additional loads ranging from 17 to 87 kg. Vertical ground reaction
      force data were recorded (1,000 Hz) and used to compute center of mass vertical
      displacement. For each condition, mean force, velocity, and power output were
      determined over the entire push-off phase of the best trial, and used to
      determine individual linear F-v relationships and P max. From a previously
      validated biomechanical model, the optimal F-v profile maximizing jumping
      performance was determined for each subject and used to compute the individual
      mechanical F-v imbalance (Fv IMB) as the difference between actual and optimal F
      v profiles. RESULTS: A multiple regression analysis clearly showed (r(2) = 0.952,
      P < 0.001, SEE 0.011 m) that P max, Fv IMB and lower limb extension range (h PO)
      explained a significant part of the interindividual differences in CMJ
      performance (P < 0.001) with positive regression coefficients for P max and h PO
      and a negative one for Fv IMB. CONCLUSION: Compared to SJ, F-v relationships were
      shifted to the right in CMJ, with higher P max, maximal theoretical force and
      velocity (+35.8, 20.6 and 13.3%, respectively). As in SJ, CMJ performance depends
      on Fv IMB, independently from the effect of P max, with the existence of an
      individual optimal F-v profile (Fv IMB having an even larger influence in CMJ).

PMID- 25048076
TI  - Hybrid crystals comprising metal-organic frameworks and functional particles:
      synthesis and applications.
AB  - Hybrid crystals containing encapsulated functional species exhibit promising
      novel physical and chemical properties. The realization of many properties
      critically depends on the selection of suitable functional species for
      incorporation, the rational control of the crystallinity of the host materials,
      and the manipulation of the distribution of the encapsulated species; only a few
      hybrid crystals achieve this. Here, a novel synthetic method enables the
      encapsulation of functional species within crystalline metal-organic frameworks
      (MOFs). Various kinds of single-crystalline MOFs with incorporated particles are
      presented. The encapsulated particles can be distributed in a controllable
      manner, and the hybrid crystals are applied to the heterogeneous catalysis of the
      reduction of nitroarenes. These findings suggest a general approach for the
      construction of MOF materials with potential applications; by combining species
      and MOFs with suitable functionalities, new properties--not possible by other
      means--may arise.

PMID- 25048074
TI  - Early-phase musculoskeletal adaptations to different levels of eccentric
      resistance after 8 weeks of lower body training.
AB  - PURPOSE: Eccentric muscle actions are important to the development of muscle mass
      and strength and may affect bone mineral density (BMD). This study's purpose was
      to determine the relative effectiveness of five different eccentric:concentric
      load ratios to increase musculoskeletal parameters during early adaptations to
      resistance training. METHODS: Forty male subjects performed a supine leg press
      and calf press training program 3 days week(-1) for 8 weeks. Subjects were
      matched for pre-training leg press 1-repetition maximum strength (1-RM) and
      randomly assigned to one of five training groups. Concentric training load (% 1
      RM) was constant across groups, but within groups, eccentric load was 0, 33, 66,
      100, or 138% of concentric load. Muscle mass (dual energy X-ray absorptiometry;
      DXA), strength (1-RM), and BMD (DXA) were measured pre- and post-training.
      Markers of bone metabolism were assessed pre-, mid- and post-training. RESULTS:
      The increase in leg press 1-RM in the 138% group (20 +/- 4%) was significantly
      greater (P < 0.05) than the 0% (8 +/- 3%), 33% (8 +/- 5%) and 66% (8 +/- 4%)
      groups, but not the 100% group (13 +/- 6 %; P = 0.15). All groups, except the 0%
      group, increased calf press 1-RM (P < 0.05). Leg lean mass and greater trochanter
      BMD were increased only in the 138% group (P < 0.05). CONCLUSIONS: Early-phase
      adaptations to eccentric overload training include increases in muscle mass and
      site-specific increases in BMD and muscle strength which are not present or are
      less with traditional and eccentric underload training. Eccentric overload
      provides a robust musculoskeletal stimulus that may benefit bedridden patients,
      individuals recovering from injury or illness, and astronauts during spaceflight.

PMID- 25048075
TI  - Small-sided games training reduces CRP, IL-6 and leptin in sedentary, middle-aged
      men.
AB  - PURPOSE: Long-term physical activity is reported to improve chronic systemic
      inflammation, which provides protection against the ensuing development of
      chronic disease. Accordingly, the present study assessed changes in pro- and anti
      inflammatory cytokines, aerobic capacity and body composition following 8 weeks
      of either small-sided games (SSG) or cycling (CYC) training compared to a
      sedentary control (CON) condition. METHODS: Thirty-three middle-aged, sedentary
      men were randomized into CYC (n = 11), SSG (n = 11), or CON (n = 11) conditions.
      The CYC and SSG conditions trained 3 days/week for 8 weeks, whilst CON maintained
      habitual activity and dietary patterns. Pre- and post-intervention testing
      included a dual-energy X-ray absorptiometry scan, sub-maximal (80% maximal heart
      rate) aerobic capacity (VO2) and fasting venous blood. Venous blood measures for
      pro-inflammatory markers included C-reactive protein (CRP), interleukin (IL)-6,
      IL-1beta, tumor necrosis factor-alpha, and leptin; anti-inflammatory markers
      included IL-10, IL-1 receptor agonist, and adiponectin. RESULTS: Both CYC and SSG
      increased submaximal power output and VO2 (P < 0.05), decreased total body fat
      mass (TB-FM; P < 0.05), and CRP (SSG, -0.45 +/- 0.42 mg L(-1); P = 0.008; CYC, 
      0.44 +/- 0.59 mg L(-1); P = 0.02). Only SSG increased total body fat-free mass
      (TB-FFM; +1.1 +/- 1.2 kg; P = 0.001) and decreased concentration of plasma IL-6 (
      0.69 +/- 0.62 pg mL(-1); P = 0.002) and leptin (-2,212 +/- 2,531 ng mL(-1); P =
      0.014). CONCLUSION: Cycling and SSG training were both effective at improving
      CRP, VO2 and TB-FM. Furthermore, SSG training has also shown to be an effective
      training approach in reducing IL-6 and leptin and increasing muscle mass within
      sedentary, middle-aged men.

PMID- 25048077
TI  - Peltate glandular trichomes of Colquhounia seguinii harbor new defensive
      clerodane diterpenoids.
AB  - Glandular trichomes produce a wide variety of secondary metabolites that are
      considered as major defensive chemicals against herbivore attack. The morphology
      and secondary metabolites of the peltate glandular trichomes of a lianoid
      Labiatae, Colquhounia seguinii Vaniot, were investigated. Three new clerodane
      diterpenoids, seguiniilactones A-C (1-3), were identified through precise
      trichome collection with laser microdissection, metabolic analysis with ultra
      performance liquid chromatography-tandem mass spectrometer, target compound
      isolation with classical phytochemical techniques, structure elucidation with
      spectroscopic methods. All compounds showed significant antifeedant activity
      against a generalist plant-feeding insect Spodoptera exigua. Seguiniilactone A
      (1) was approximately 17-fold more potent than the commercial neem oil. alpha
      Substituted alpha,beta-unsaturated gamma-lactone functionality was found to be
      crucial for strong antifeedant activity of this class of compounds. Quantitative
      results indicated that the levels of these compounds in the peltate glandular
      trichomes and leaves were sufficiently high to deter the feeding by generalist
      insects. Moderate antifungal activity was observed for seguiniilactone C (3)
      against six predominant fungal species isolated from the diseased leaves of C.
      seguinii, while seguiniilactones A and B were generally inactive. These findings
      suggested that seguiniilactones A-C might be specialized secondary metabolites in
      peltate glandular trichomes for the plant defense against insect herbivores and
      pathogens. 

PMID- 25048078
TI  - Immunoglobulin G antibodies to the N-Methyl-D-aspartate receptor are distinct
      from immunoglobulin A and immunoglobulin M responses.

PMID- 25048079
TI  - Polyamory: a call for increased mental health professional awareness.

PMID- 25048080
TI  - Purported changes in pedophilia as statistical artefacts: comment on Muller et
      Al. (2014).

PMID- 25048081
TI  - Resting complexes of the persistent yeast 20S RNA Narnavirus consist solely of
      the 20S RNA viral genome and its RNA polymerase p91.
AB  - The positive strand 20S RNA narnavirus persistently infects Saccharomyces
      cerevisiae. The 20S RNA genome has a single gene that encodes the RNA-dependent
      RNA polymerase (p91). 20S RNA forms ribonucleoprotein resting complexes (RNPs)
      with p91 and resides in the cytoplasm. Here we found no host proteins
      stoichiometrically associated with the RNP by pull-down experiments. Furthermore,
      20S RNA, when expressed from a vector in Escherichia coli, formed RNPs with p91
      in the absence of yeast proteins. This interaction required the 3' cis signal for
      complex formation. Moreover, when 23S RNA, the genome of another narnavirus, was
      expressed in E. coli, it also formed RNPs with its RNA polymerase p104. Finally,
      when both RNAs were expressed in the same E. coli cell, they formed RNPs only
      with their cognate RNA polymerases. These results altogether indicate that
      narnaviruses RNPs consist of only the viral genomes and their cognate RNA
      polymerases. Because the copy number of the RNPs can be induced almost equivalent
      to those of rRNAs in some yeast strains, the absence of host proteins may
      alleviate the burden on the host by not sequestering proteins into the RNPs. It
      may also contribute to the persistent infection of narnaviruses by decreasing
      their visibility. 

PMID- 25048082
TI  - Progress in macromolecular crystallography depends on further miniaturization of
      crystallization experiments.

PMID- 25048083
TI  - MicroRNA: a small molecule with a big biological impact.
AB  - One of the most significant achievements in biological science in the last decade
      is the discovery of RNA interference (RNAi), a process within living cells that
      regulates gene expression at post-transcriptional levels. Historically, this
      process was described by other more generic names, such as co-suppression and
      post transcriptional gene silencing. Only after the molecular mechanism
      underlying these apparently unrelated processes was fully understood did it
      become apparent that they all described the RNAi phenomenon. In 2006, Dr. Andrew
      Fire and Dr. Craig C. Mello were awarded the Nobel Prize in Physiology or
      Medicine for their work on RNAi interference. RNAi is an RNA-dependent gene
      silencing process that is controlled by the RNA-induced silencing complex (RISC)
      and is initiated by two types of small RNA molecules - microRNA (miRNA) and small
      interfering RNA (siRNA). However, the function of microRNA appears to be far
      beyond RNAi alone, including direct interaction with the gene promoter and
      epigenetic regulation of the DNA methylation and histone modification. By
      regulating gene expression, miRNAs are likely to be involved in diverse
      biological activities, such as tumorigenesis, immune response, insulin secretion,
      neurotransmitter synthesis, and circadian rhythm, to name a few. MicroRNAs are 21
      23 nucleotide single stranded RNA molecules found in eukaryotic cells. The first
      miRNA, lin-4, was characterized in C. elegans in the early 1990s [1]. In the
      early years, the progress on microRNA research was slow and experienced
      substantial growing pains. The short length and uniqueness of each microRNA
      rendered many conventional hybridization based methods ineffective; very small
      RNAs are difficult to reliably amplify or label without introducing bias. In
      addition, hybridization-based methods for microRNA profiling relied on probes
      designed to detect known microRNAs or known microRNA species previously
      identified by sequencing or homology search. Recent evidence of target-directed
      editing of mature microRNA (trimming and tailing by 3'-to-5' exonuclase and
      terminal nucleotide transferase) [2] further highlighted the complexity of
      microRNA processing and regulation mechanisms. Moreover, the wide range of
      microRNA expression, from tens of thousands to just few molecules per cell,
      complicated the detection of microRNAs expressed at low copy numbers. Hence, many
      novel microRNAs may exist even in well-explored species. Nevertheless, recent
      advances in genomic technologies and data analysis / bioinformatics approaches
      have made a significant impact on microRNA research. For example, next generation
      deep sequencing platforms are ideal for detecting and quantifying both known and
      novel microRNA sequences with high sensitivity and for a relatively low cost [3].
      The microRNA field has experienced a major explosion in recent years. The
      microRNA gene family is continuously growing with novel members discovered in
      association with rapid advances in genomic technologies, and reports on the
      functional characterizations of specific microRNA genes have been dominating the
      recent literature. We devote this new journal, MicroRNA, to the rapidly advancing
      field of microRNA research. We dedicate our new journal to the scientists who
      work tirelessly on this family of small molecules, and their immense
      contributions to the biological sciences. MicroRNA publishes letters, full-length
      research articles, review articles, drug and clinical trial studies and thematic
      issues on all aspects of microRNA research. The scope of the journal covers all
      experimental microRNA research and applied research in the fields of health and
      disease, including therapeutic, biomarker, and diagnostic applications of
      microRNA. 

PMID- 25048084
TI  - MicroRNA-155 functions as a negative regulator of RhoA signaling in TGF-beta
      induced endothelial to mesenchymal transition.
AB  - Endothelial to mesenchymal transition (EndoMT) has been proposed to be involved
      in the loss of microvascular capillaries in the pathophysiology of fibrosis and
      organ failure. In EndoMT, endothelial cells (EC) undergo a mesenchymal transition
      associated with the loss of cell-cell contacts and the acquisition of a
      synthetic, contractile phenotype. Here, we sought to identify microRNAs (miRNAs)
      that could play a central role in regulating EndoMT. In a TGF-beta dependent in
      vitro model for EndoMT, we identified miRNAs that were differentially expressed
      in normoxic and hypoxic conditions. These studies identified miR-155 to be
      significantly upregulated in EndoMT, an effect that was enhanced under hypoxia,
      which further augments EndoMT. Silencing of miR-155 directly increased RhoA
      expression and activity in endothelial cells and affected phosphorylation of
      downstream LIMK. In contrast, overexpression of miR-155 counteracted RhoA
      function. Using a selective Rho kinase inhibitor, we could partly suppress
      EndoMT, strengthening the notion that RhoA plays a central role in EndoMT. Forced
      overexpression of miR-155 completely suppressed EndoMT, as evidenced by the
      maintenance of EC characteristics and blocking the acquisition of a mesenchymal
      phenotype, as compared to control cells. Our data demonstrate that miRNA-155
      functions as a negative regulator of RhoA signaling in TGF-beta-induced
      endothelial to mesenchymal transition. 

PMID- 25048085
TI  - Investigating the in vivo expression patterns of miR-7 microRNA family members in
      the adult mouse brain.
AB  - MicroRNAs (miRNAs) are endogenous non-coding RNAs that play critical roles in
      regulating transcription in eukaryotes. miRNAs are involved in a wide-range of
      biological processes. Because miRNA research is relatively new, it is not
      surprising that tools and techniques to study their biology are still being
      developed. Our laboratory is interested in carefully delineating the in vivo
      expression patterns between three closely related miR-7 miRNA family members in
      the mouse. The miR-7 family of miRNAs is conserved between humans and
      invertebrates. The miR-7 family also shows conserved expression in neural
      tissues, and members of this family are involved in the development of sensory
      structures in flies, associated with many types of cancer, and likely play a role
      in osmoregulation in the mouse brain. In this study, we used multiple methods to
      differentiate the expression of the miR-7 family members in the mouse brain. Our
      results suggest that although there are useful tools for exploring miRNA
      expression in vivo, better tools and/or methods are still needed for thorough in
      vivo studies of closely related family members. 

PMID- 25048086
TI  - Efficient silencing of hepatitis B virus by helper-dependent adenovirus vector
      mediated delivery of artificial antiviral primary micro RNAs.
AB  - Hepatitis B virus (HBV) infection is endemic to southern Africa and parts of Asia
      where approximately 350 million individuals are chronically infected. Persistent
      infection increases risk for the serious complications of cirrhosis and
      hepatocellular carcinoma. Licensed HBV treatments rarely eradicate the virus,
      which makes developing new strategies for the treatment of chronic HBV a
      priority. Pol II-transcribed mono- and trimeric primary micro RNAs (primiRNAs)
      have previously been used to activate RNA interference (RNAi) and inhibit HBV
      gene expression, indicating that this approach holds promise for HBV therapy.
      Nevertheless, achieving safe and efficient delivery of anti-HBV RNAi expression
      cassettes remains an important objective before therapeutic application of this
      gene silencing technology is realized. Recombinant adenoviruses (Ads) are amongst
      the most efficient hepatotropic gene delivery vehicles, but a drawback of their
      use is transient transgene expression and toxicity that results from induction of
      host immune responses. To diminish immunostimulation of anti-HBV RNAi-activating
      vectors, helper-dependent (HD) Ads with all viral proteinencoding sequences
      removed from their genomes, were generated. A CMV Pol II promoter element was
      used to transcribe antiviral pri-miRNAs that target HBV. Processing of the anti
      HBV pri-miRNA RNAi activators occurred according to intended design. Assessment
      in cultured cells and in a HBV transgenic model of the infection demonstrated
      that HD Ads delivered the silencing sequences efficiently and replication of the
      virus was inhibited without causing overt toxic effects. Collectively these data
      augur well for clinical use of HD Ads to deliver Pol II HBV-silencing cassettes
      to counter the persistent infection. 

PMID- 25048087
TI  - Involvement of microRNA181a in differentiation and cell cycle arrest induced by a
      plant-derived antioxidant carnosic acid and vitamin D analog doxercalciferol in
      human leukemia cells.
AB  - 1,25-dihydroxyvitamin D3 (1,25D) has been shown to influence differentiation,
      cell proliferation and cell death in cultured leukemia cells. However, its
      clinical use is limited by its hypercalcemic effects. An analog of 1,25D,
      doxercalciferol (1-D2), has anti-tumor activity, with markedly reduced calcemic
      effects, which makes it a potential agent for clinical treatment of AML. Previous
      studies suggested that the combination of 1,25D with other agents, such as plant
      derived antioxidants, can have additive or synergistic anti-cancer activities in
      leukemia cells. Here we report that 1-D2 induced monocytic differentiation of
      HL60 and U937 cells, and that the antioxidant carnosic acid (CA) enhanced 1-D2
      induced differentiation and cell cycle arrest. MicroRNA181a (miR181a) expression
      was also reduced after exposure to CA/1-D2. Since the cell cycle regulator
      p27Kip1 has been shown to be a target of miR181a, we modulated miR181a levels to
      determine if it plays a role in CA/1-D2 induced differentiation and cell cycle
      arrest in AML cells. We found that transfection of antisense miR181a potentiated
      CA/1-D2-induced cell differentiation, while the transfection of precursor of
      miR181a partially inhibited the effect of CA/1-D2 on the differentiation. These
      findings imply that miR181a has a role in CA/1-D2- induced differentiation and
      cell cycle arrest of HL60 and U937 cells, and shows a broader participation of
      miR181a in cell cycle control in leukemia cells. 

PMID- 25048088
TI  - Function and regulation of let-7 family microRNAs.
AB  - MicroRNAs (miRNAs) are a group of small noncoding RNAs capable of regulating
      specific gene expression. Let-7 miRNA was first discovered in Caenorhabditis
      elegans and it is highly conserved in human tissues. The human let- 7 family of
      miRNA contains 12 members of miRNA. Today, these members have become the most
      studied miRNAs and they have attracted attention of researchers in various
      fields, such as development, stem cell biology, aging, and metabolism.
      Furthermore, there is a large body of evidence linking the loss of let-7
      expression and the development of poorly differentiated, aggressive cancers. In
      addition to the canonical biogenesis pathway, let-7 has been found to be
      regulated by protein factors, such as RNA binding proteins previously identified
      as regulators of protein-coding mRNAs. Moreover, the direct interaction between
      miRNAs has recently been identified as a novel pathway to control let-7
      expression. In this review, we discuss the multifaceted roles of let-7 and
      provide an overview of its regulation at multiple levels. 

PMID- 25048089
TI  - The role of microRNAs in the diagnosis and treatment of malignant pleural
      mesothelioma--a short review.
AB  - MicroRNAs are a class of small, non-coding RNAs that can function as tumor
      suppressors or oncogenes by regulating gene expression. This link was first
      reported in 2004, and has since been tied to a variety of malignancies, including
      malignant pleural mesothelioma (MPM). MPM is a malignancy arising in the
      mesothelial cells lining the lung pleura and is associated with chronic asbestos
      exposure. Despite the possibility for observing declining localized occurrence,
      global MPM is predicted to remain constant or increase slightly over the next
      decade. Global occurrence in combination with poor overall survival, difficulty
      in diagnosis, and limited effective treatment options signal the need for further
      exploration of miRNA involvement in MPM. Accordingly, this review highlights
      miRNA profiles associated with the diagnosis, prognosis, and therapeutic
      approaches in MPM. 

PMID- 25048090
TI  - No miR quirk: dysregulation of microRNAs in pancreatic ductal adenocarcinoma.
AB  - MicroRNAs are post-transcriptional regulators of gene expression with tissue
      specific expression profiles. Dysregulation of microRNAs has been shown to play a
      role in carcinogenesis. Although progress has been made in the diagnosis and
      treatment of many cancers, pancreatic cancer remains an intractable public health
      problem, causing 6.58% of cancer deaths despite making up less than 3% of cancer
      diagnoses in the United States. No screening, diagnostic or imaging techniques
      exist with the sensitivity to detect pancreatic cancer in its early, operable
      stages. Risk factors include numerous inherited syndromes, diabetes mellitus, and
      hepatitis C virus infection. Here we review the literature regarding
      dysregulation of microRNA expression in native pancreas, pancreatic ductal
      adenocarcinoma (the dominant form of pancreatic cancer), and its risk factors to
      illuminate the biology and progression of this disease. We explore promising
      evidence for the use of microRNAs as prognostic and diagnostic tools, and discuss
      emerging reports on microRNA therapeutics. 

PMID- 25048091
TI  - A macro role for imprinted clusters of microRNAs in the brain.
AB  - Evidence suggests that ~95% of the human genome may produce noncoding RNAs
      (ncRNAs). Approximately 30% of parentally imprinted transcripts are ncRNAs that
      are found abundantly--and in some cases specifically--in the brain; however, the
      role ncRNA plays during development and day-to-day life is not apparent.
      Interestingly, ~1,300 transcripts show a consistent parental expression bias in
      the brain. This is in contrast to most tissues that show only rare imprinted
      transcripts. Furthermore, there are only two clusters of imprinted small
      nucleolar RNA (snoRNA) encoding genes in mammals, which are also expressed in the
      brain. These clusters, Snrpn-Ube3a (Human 15q11-q13/Murine 7qC) and Dlk1-Dio3
      (Human 14q32.2/Murine 12qF1) and rodent specific Sfmbt2 (Murine 2qA1), form the
      focus of this review. These imprinted clusters are localized to imprinted regions
      that are associated with processes involved in neuronal plasticity and several
      neurodevelopmental disorders. Several miRNAs from the Dlk1-Dio3 region are also
      involved in chromatin methylation and remodelling. The final loci of interest is
      the proximal region of murine chromosome 2 that contains Sfmbt2 and an
      overlapping antisense transcript that is unique within mice and rats. This
      suggests that Sfmbt2 may be in the process of becoming imprinted that is being
      driven by a cluster of intergenic miRNAs. Ultimately, imprinted clusters of ncRNA
      have the potential to offer novel insight into the understanding of the complex
      processes of cognition given their role in brain function.

PMID- 25048092
TI  - miR-21 and let-7 in the Ras and NF-kappaB pathways.
AB  - miR-21 and let-7 are two of the most studied microRNAs (miRNAs), as the former is
      the most frequently upregulated and the latter is the most frequently down
      regulated in cancer. In this short essay, we examine the convergence of miR-21
      and let-7 in two major cancer pathways: Ras and NF-kappaB. miR-21 suppresses
      multiple targets to enhance the oncogenic action of Ras, while let-7 is a direct
      negative regulator of the Ras gene family. let-7 is proposed to repress the
      activation of NF-kappaB through down-regulation of Ras and IL-6, while miR-21 is
      demonstrated to enhance NF-kappaB activation by down-regulating Pten and thereby
      increasing the activity of Akt, a kinase known to promote the NF-kappaB pathway.
      Therefore, miR-21 and let-7 contravene each other in cancer and simultaneous
      targeting of both is an attractive therapeutic strategy against cancers
      exhibiting both Ras mutations and constitutive NF-kappaB activation. 

PMID- 25048094
TI  - Sustainability of meat production beyond carbon footprint: a synthesis of case
      studies from grazing systems in Uruguay.
AB  - Livestock production has been challenged as a large contributor to climate
      change, and carbon footprint has become a widely used measure of cattle
      environmental impact. This analysis of fifteen beef grazing systems in Uruguay
      quantifies the range of variation of carbon footprint, and the trade-offs with
      other relevant environmental variables, using a partial life cycle assessment
      (LCA) methodology. Using carbon footprint as the primary environmental indicator
      has several limitations: different metrics (GWP vs. GTP) may lead to different
      conclusions, carbon sequestration from soils may drastically affect the results,
      and systems with lower carbon footprint may have higher energy use, soil erosion,
      nutrient imbalance, pesticide ecotoxicity, and impact on biodiversity. A
      multidimensional assessment of sustainability of meat production is therefore
      needed to inform decision makers. There is great potential to improve grazing
      livestock systems productivity while reducing carbon footprint and other
      environmental impacts, and conserving biodiversity. 

PMID- 25048095
TI  - Process-induced undesirable compounds: chances of non-thermal approaches.
AB  - During the processing of meat and meat products the generation of undesirable
      compounds can occur. Known examples are the generation of substances that can
      lead to a negative effect on the texture, flavour or colour of products after
      processing or during storage. Furthermore, thermal processing and smoking have
      been associated with the generation of or contamination with toxic substances,
      e.g. polycyclic aromatic hydrocarbons or heterocyclic amines. The introduction of
      new processing technologies may result in the formation of different undesirable
      compounds compared to traditional technologies. Some of these changes may be
      without relevant nutritional or health impact, while others may raise concern. To
      begin with, an overview on the formation of undesirable process-induced compounds
      by the traditional processing of meat and the proposed strategies for their
      reduction is presented. Hereby attention is mainly paid to those compounds which
      present human health concerns. Later the focus lays on the process-induced
      modifications occurring in meat as a result of high hydrostatic pressure
      treatments. 

PMID- 25048093
TI  - Functional interactions between microRNAs and RNA binding proteins.
AB  - Ensuring the appropriate spatial-temporal control of protein abundance requires
      careful control of transcript levels. This process is regulated at many steps,
      including the rate at which transcripts decay. microRNAs (miRNAs) and RNA Binding
      Proteins (RBPs) represent two important regulators of transcript degradation. We
      review here recent literature that suggests these two regulators of transcript
      decay may functionally interact. Some studies have reported an excess of miRNA
      binding sites surrounding the positions at which RBPs bind. Experimental reports
      focusing on a particular transcript have identified instances in which RBPs and
      miRNAs compete for the same target sites, and instances in which the binding of a
      RBP makes a miRNA recognition site more accessible to the RISC complex. Further,
      miRNAs and RBPs use similar enzymes for degradation of target transcripts and the
      degradation of the target transcripts occurs in similar subcellular compartments.
      In addition to miRNA-RBP interactions involving transcript decay, RBPs have also
      been reported to facilitate the processing of pri-miRNAs to their final form. We
      summarize here several possible mechanisms through which miRNA-RBP interactions
      may occur. 

PMID- 25048096
TI  - Growth, carcass traits and palatability: can the influence of the feeding regimes
      explain the variability found on those attributes in different Uruguayan
      genotypes?
AB  - It is well known what genetic and nutritional factors affect growth and meat
      quality, but there is less information related to interactive importance of them
      during the productive process. These systems are mainly based on rangelands
      affecting animal growth in early stages of life thus producing smaller cattle and
      reduced retail yield comparing with well grown calves. During the last ten years,
      Uruguayan livestock production systems have been intensified using improved
      pastures, concentrates and better genetic. The main breeds in Uruguay are
      Hereford, Angus and their crosses. These British breeds are under genetic
      evaluation programs which consider carcass trait parameters. It is important for
      beef industry to know if interactions between genotype and nutrition during
      growth and fattening phases are influencing production, efficiency, carcass
      weight and meat quality attributes. The aim of this article is to present
      information obtained under different feeding strategies during the post weaning
      and fattening and their influence on those attributes. 

PMID- 25048097
TI  - Fibrous nodules over the patella revealing acrodermatitis chronica atrophicans.

PMID- 25048098
TI  - Toxidermia under treatment with tocilizumab for rheumatoid arthritis.

PMID- 25048099
TI  - Ataxic dysarthria revealing Fahr's syndrome and hypoparathyroidism.

PMID- 25048100
TI  - The World War I (1914-1918) and rheumatology.

PMID- 25048101
TI  - Pulmonary hyalinizing granuloma associated with Sjogren syndrome and ANCA MPO
      vasculitis.

PMID- 25048102
TI  - Health related quality of life and influencing factors among welders.
AB  - BACKGROUND: Occupational exposure to welding fumes is a serious occupational
      health problem all over the world. Welders are exposed to many occupational
      hazards; these hazards might cause some occupational diseases. The aim of the
      study was to assess the health related quality of life (HRQL) of electric welders
      in Shanghai China and explore influencing factors to HRQL of welders. METHODS:
      301 male welders (without pneumoconiosis) and 305 non-dust male workers in
      Shanghai were enrolled in this study. Short Form-36 (SF-36) health survey
      questionnaires were applied in this cross-sectional study. Socio-demographic,
      working and health factors were also collected. Multiple stepwise regress
      analysis was used to identify significant factors related to the eight dimension
      scores. RESULTS: Six dimensions including role-physical (RP), bodily pain (BP),
      general health (GH), validity (VT), social function (SF), and mental health (MH)
      were significantly worse in welders compared to non-dust workers. Multiple
      stepwise regress analysis results show that native place, monthly income,
      quantity of children, drinking, sleep time, welding type, use of personal
      protective equipment (PPE), great events in life, and some symptoms including
      dizziness, discomfort of cervical vertebra, low back pain, cough and insomnia may
      be influencing factors for HRQL of welders. Among these factors, only sleep time
      and the use of PPE were salutary. CONCLUSIONS: Some dimensions of HRQL of these
      welders have been affected. Enterprises which employ welders should take measures
      to protect the health of these people and improve their HRQL.

PMID- 25048103
TI  - The impact of different surgical modalities for hysterectomy on satisfaction and
      patient reported outcomes.
AB  - BACKGROUND: There is an ongoing debate regarding the cost-benefit of different
      surgical modalities for hysterectomy. Studies have relied primarily on evaluation
      of clinical outcomes and medical expenses. Thus, a paucity of information on
      patient-reported outcomes including satisfaction, recovery, and recommendations
      exists. OBJECTIVE: The objective of this study was to identify differences in
      patient satisfaction and recommendations by approach to a hysterectomy. METHODS:
      We recruited a large, geographically diverse group of women who were members of
      an online hysterectomy support community. US women who had undergone a benign
      hysterectomy formed this retrospective study cohort. Self-reported
      characteristics and experiences were compared by surgical modality using chi
      square tests. Outcomes over time were assessed with the Jonkheere-Terpstra trend
      test. Logistic regression identified independent predictors of patient
      satisfaction and recommendations. RESULTS: There were 6262 women who met the
      study criteria; 41.74% (2614/6262) underwent an abdominal hysterectomy, 10.64%
      (666/6262) were vaginal, 27.42% (1717/6262) laparoscopic, 18.94% (1186/6262)
      robotic, and 1.26% (79/6262) single-incision laparoscopic. Most women were at
      least college educated (56.37%, 3530/6262), and identified as white, non-Hispanic
      (83.17%, 5208/6262). Abdominal hysterectomy rates decreased from 68.2% (152/223)
      to 24.4% (75/307), and minimally invasive surgeries increased from 31.8% (71/223)
      to 75.6% (232/307) between 2001 or prior years and 2013 (P<.001 all trends).
      Trends in overall patient satisfaction and recommendations showed significant
      improvement over time (P<.001).There were differences across the surgical
      modalities in all patient-reported experiences (ie, satisfaction, time to
      walking, driving and working, and whether patients would recommend or use the
      same technique again; P<.001). Significantly better outcomes were evident among
      women who had vaginal, laparoscopic, and robotic procedures than among those who
      had an abdominal procedure. However, robotic surgery was the only approach that
      was an independent predictor of better patient experience; these patients were
      more satisfied overall (odds ratio [OR] 1.31, 95% CI 1.13-1.51) and on six other
      satisfaction measures, and more likely to recommend (OR 1.64, 95% CI 1.39-1.94)
      and choose the same modality again (OR 2.07, 95% CI 1.67-2.57). Abdominal
      hysterectomy patients were more dissatisfied with outcomes after surgery and less
      likely to recommend (OR 0.36, 95% CI 0.31-0.40) or choose the same technique
      again (OR 0.29, 95% CI 0.25-0.33). Quicker return to normal activities and
      surgery after 2007 also were independently associated with better overall
      satisfaction, willingness to recommend, and to choose the same surgery again.
      CONCLUSIONS: Consistent with other US data, laparoscopic and robotic hysterectomy
      rates increased over time, with a concomitant decline in abdominal hysterectomy.
      While inherent shortcomings of this retrospective Web-based study exist, findings
      show that patient experience was better for each of the major minimally invasive
      approaches than for abdominal hysterectomy. However, robotic-assisted
      hysterectomy was the only modality that independently predicted greater
      satisfaction and willingness to recommend and have the same procedure again.

PMID- 25048104
TI  - Classification of independent components of EEG into multiple artifact classes.
AB  - In this study, we aim to automatically identify multiple artifact types in EEG.
      We used multinomial regression to classify independent components of EEG data,
      selecting from 65 spatial, spectral, and temporal features of independent
      components using forward selection. The classifier identified neural and five
      nonneural types of components. Between subjects within studies, high
      classification performances were obtained. Between studies, however,
      classification was more difficult. For neural versus nonneural classifications,
      performance was on par with previous results obtained by others. We found that
      automatic separation of multiple artifact classes is possible with a small
      feature set. Our method can reduce manual workload and allow for the selective
      removal of artifact classes. Identifying artifacts during EEG recording may be
      used to instruct subjects to refrain from activity causing them. 

PMID- 25048105
TI  - Feasibility of the assessment of cholesterol crystals in human macrophages using
      micro optical coherence tomography.
AB  - The presence of cholesterol crystals is a hallmark of atherosclerosis, but until
      recently, such crystals have been considered to be passive components of necrotic
      plaque cores. Recent studies have demonstrated that phagocytosis of cholesterol
      crystals by macrophages may actively precipitate plaque progression via an
      inflammatory pathway, emphasizing the need for methods to study the interaction
      between macrophages and crystalline cholesterol. In this study, we demonstrate
      the feasibility of detecting cholesterol in macrophages in situ using Micro
      Optical Coherence Tomography (uOCT), an imaging modality we have recently
      developed with 1-um resolution. Macrophages containing cholesterol crystals
      frequently demonstrated highly scattering constituents in their cytoplasm on uOCT
      imaging, and uOCT was able to evaluate cholesterol crystals in cultured
      macrophage cells. Our results suggest that uOCT may be useful for the detection
      and characterization of inflammatory activity associated with cholesterol
      crystals in the coronary artery. 

PMID- 25048107
TI  - Driving knots on DNA with AC/DC electric fields: topological friction and memory
      effects.
AB  - The dynamical properties of entangled polyelectrolytes are investigated
      theoretically and computationally for a proposed novel micromanipulation setup.
      Specifically, we investigate the effects of DC and AC electric fields acting
      longitudinally on knotted DNA chains, modelled as semiflexible chains of charged
      beads, under mechanical tension. We consider various experimentally accessible
      values of the field amplitude and frequency as well as several of the simplest
      knot types. In particular, we consider both torus and twist knots because they
      are respectively known to be able or unable to slide along macroscopic threads
      and ropes. Strikingly, this qualitative distinction disappears in this
      microscopic context because all the considered knot types acquire a systematic
      drift in the direction of the electric force. Notably, the knot drift velocity
      and diffusion coefficient in zero field (both measurable also experimentally) can
      be used to define a characteristic "frictional" lengthscale for the various knot
      types. This previously unexplored length provides valuable information on the
      extent of self-interactions in the nominal knotted region. It is finally observed
      that the motion of a knot can effectively follow the AC field only if the driving
      period is larger than the knot relaxation time (for which the self-diffusion time
      provides an upper bound). These results suggest that salient aspects of the
      intrinsic dynamics of knots in DNA chains could be probed experimentally by means
      of external, time-dependent electric fields. 

PMID- 25048108
TI  - Evolution with reinforcement learning in negotiation.
AB  - Adaptive behavior depends less on the details of the negotiation process and
      makes more robust predictions in the long term as compared to in the short term.
      However, the extant literature on population dynamics for behavior adjustment has
      only examined the current situation. To offset this limitation, we propose a
      synergy of evolutionary algorithm and reinforcement learning to investigate long
      term collective performance and strategy evolution. The model adopts
      reinforcement learning with a tradeoff between historical and current information
      to make decisions when the strategies of agents evolve through repeated
      interactions. The results demonstrate that the strategies in populations converge
      to stable states, and the agents gradually form steady negotiation habits. Agents
      that adopt reinforcement learning perform better in payoff, fairness, and
      stableness than their counterparts using classic evolutionary algorithm. 

PMID- 25048110
TI  - Inflammatory bone spur formation in psoriatic arthritis is different from bone
      spur formation in hand osteoarthritis.
AB  - OBJECTIVE: To investigate the different patterns of bone spur formation in
      psoriatic arthritis (PsA) and hand osteoarthritis (OA), using high-resolution
      peripheral quantitative computed tomography (QCT). METHODS: The study group
      comprised 70 subjects (25 patients with PsA, 25 patients with hand OA, and 20
      healthy controls). The 2 patient groups were similar with regard to age and sex
      distribution and clinical involvement of the metacarpophalangeal (MCP) joints.
      All patients underwent high-resolution peripheral QCT scanning of the second,
      third, and fourth MCP joints of the dominantly affected hand. Demographic and
      disease-specific data were recorded, and the number, size, and distribution of
      bone spurs were assessed and compared between patients with PsA and patients with
      hand OA. RESULTS: The overall number and size of bone spurs were similar in
      patients with PsA and patients with hand OA. However, localization of lesions
      within individual joints was substantially different between patients with PsA
      and those with hand OA. In PsA, bone spurs dominated the radial sides of the
      joints (for the metacarpal head of the second joint, P < 0.001 versus hand OA;
      for the base of the second phalangeal joint, P < 0.001 versus hand OA), whereas
      the palmar and dorsal quadrants were the predilection sites in hand OA. Detailed
      anatomic analysis showed that bone spurs in the entheseal regions were prominent
      in patients with PsA but rare in patients with hand OA, and that bone spurs in
      patients with hand OA typically emerged at the cartilage-bone interphase and the
      joint margins. CONCLUSION: Our findings show that the overall number and size of
      bone spurs are similar in patients with PsA and patients with hand OA.
      Nonetheless, the anatomic sites of bone proliferation are different between these
      2 groups of patients.

PMID- 25048109
TI  - Perinatal exposure to low-dose methoxychlor impairs testicular development in
      C57BL/6 mice.
AB  - Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male
      reproduction at toxicological doses. Humans and wild animals are exposed to MXC
      mostly through contaminated dietary intake. Higher concentrations of MXC have
      been found in human milk, raising the demand for the risk assessment of offspring
      after maternal exposure to low doses of MXC. In this study, pregnant mice (F0)
      were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their
      gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day
      21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5,
      P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development.
      Serum testosterone levels decreased, whereas estradiol levels increased. To
      understand the molecular mechanisms of exposure to MXC in male reproduction, the
      F1 testes were examined for changes in the expression of steroidogenesis- and
      spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC
      significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it
      downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin
      a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular
      development in mice. This animal study of exposure to low-dose MXC in F1 males
      suggests similar dysfunctional effects on male reproduction in humans. 

PMID- 25048112
TI  - Current trends in donor testing to detect syphilis infection.
AB  - Potential organ and tissue donors are tested to detect infection with T.
      pallidum, the etiologic agent of syphilis. Important considerations for testing
      potential donors include available specimen type and volume, turnaround time, and
      ability to distinguish between past and current infection. Aspects of syphilis
      infection that inform organ and tissue donor assay selection and interpretation
      and the principles underlying available assays are described. Serologic assays
      for syphilis are the methods most commonly used in donor testing. The two
      categories of serologic assays, treponemal and nontreponemal, have advantages and
      limitations for testing potential donors. Knowledge of the common syphilis
      testing algorithms used in clinical diagnostic testing is useful for assay
      selection in the organ and tissue donor setting. 

PMID- 25048111
TI  - PPARalpha activation attenuates amyloid-beta-dependent neurodegeneration by
      modulating Endo G and AIF translocation.
AB  - The accumulation of a large amount of amyloid-beta (Abeta42) in brain neurons is
      one of the debilitating characteristics of Alzheimer's disease. In this study, we
      determined the effects of peroxisome proliferator-activated receptor alpha
      (PPARalpha) activation on neuronal degeneration using a model of Abeta42-induced
      cytotoxicity. We found that 0.5 MUM Abeta42 induced DNA damage and apoptosis in
      NT2N cells after 6 h of treatment. Co-treatment of Abeta42-treated cells with
      Wy14643, a PPARalpha ligand, significantly increased cell viability after 24 h
      compared with cells treated with Abeta42 alone. There were no differences in the
      protein levels of caspase-3, Bcl-2/Bax or p53 between cells treated with Abeta42
      alone and those treated with both Abeta42 and Wy14643. However, the addition of
      Wy14643 significantly suppressed the Abeta42-induced upregulation of Endo G and
      AIF protein levels. Immunohistochemical analyses further demonstrated that
      Wy14643 reduced the expression of Endo G and AIF translocated from the cytoplasm
      into the nucleus, which occurred concomitantly with the decrease in DNA damage in
      Abeta42-treated cells. Our data clearly show that PPARalpha activation prevents
      DNA damage and neuronal cell apoptosis by decreasing the expression and
      translocation of AIF/Endo G to the nucleus in a caspase-3- and p53-independent
      pathway in the NT2N cell model. This role of PPARalpha in promoting neuron
      survival suggests a possible clinical application in treating Abeta42-associated
      neurotoxicity in Alzheimer's disease.

PMID- 25048113
TI  - Epigenetic regulation of resistance to emotional stress: possible involvement of
      5-HT1A receptor-mediated histone acetylation.
AB  - The ability to resist stress is an important defensive function of a living body.
      Thus, elucidation of the mechanisms by which the brain resists stress could help
      to pave the way for new therapeutic strategies for stress-related psychiatric
      disorders including depression. The present review focuses on the roles of brain
      5-HT1A receptor-mediated epigenetic mechanisms in the development of resistance
      to emotional stress. Behavioral pharmacological studies have demonstrated that
      treatment with a 5-HT1A receptor agonist 24 h before testing suppressed the
      decrease in emotional behaviors induced by acute restraint stress. Studies with
      DNA microarray technology have revealed that histone deacetylase genes were
      decreased in the hippocampus of mice that had been pretreated with a 5-HT1A
      receptor agonist 24 h beforehand. This preliminary finding was supported by data
      that hippocampal acetylated histone H3 was increased in mice that had developed
      emotional resistance to acute restraint stress by 5-HT1A receptor agonist.
      Furthermore, the histone deacetylase inhibitor trichostatin A also protected
      against the emotional changes induced by acute restraint stress, accompanied by
      the induction of histone H3 acetylation. These findings suggest that epigenetic
      mechanisms that are functionally coupled with 5-HT1A receptors may play a key
      role in the development of resistance to emotional stress. 

PMID- 25048114
TI  - Nanoporous membranes enable concentration and transport in fully wet paper-based
      assays.
AB  - Low-cost paper-based assays are emerging as the platform for diagnostics
      worldwide. Paper does not, however, readily enable advanced functionality
      required for complex diagnostics, such as analyte concentration and controlled
      analyte transport. That is, after the initial wetting, no further analyte
      manipulation is possible. Here, we demonstrate active concentration and transport
      of analytes in fully wet paper-based assays by leveraging nanoporous material
      (mean pore diameter ~ 4 nm) and ion concentration polarization. Two classes of
      devices are developed, an external stamp-like device with the nanoporous material
      separate from the paper-based assay, and an in-paper device patterned with the
      nanoporous material. Experimental results demonstrate up to 40-fold concentration
      of a fluorescent tracer in fully wet paper, and directional transport of the
      tracer over centimeters with efficiencies up to 96%. In-paper devices are applied
      to concentrate protein and colored dye, extending their limits of detection from
      ~10 to ~2 pmol/mL and from ~40 to ~10 MUM, respectively. This approach is
      demonstrated in nitrocellulose membrane as well as paper, and the added cost of
      the nanoporous material is very low at ~0.015 USD per device. The result is a
      major advance in analyte concentration and manipulation for the growing field of
      low-cost paper-based assays. 

PMID- 25048116
TI  - A brief outline of the immune system.
AB  - The various cells and proteins responsible for immunity constitute the immune
      system, and their orchestrated response to defend foreign/non-self substances
      (antigen) is known as the immune response. When an antigen attacks the host
      system, two distinct, yet interrelated, branches of the immune system are active
      the nonspecific/innate and specific/adaptive immune response. Both of these
      systems have certain physiological mechanisms, which enable the host to recognize
      foreign materials to itself and to neutralize, eliminate, or metabolize them.
      Innate immunity represents the earliest development of protection against
      antigens. Adaptive immunity has again two branches-humoral and cell mediated. It
      should be noted that both innate and adaptive immunities do not work
      independently. Moreover, most of the immune responses involve the activity and
      interplay of both the humoral and the cell-mediated immune branches of the immune
      system. We have described these branches in detail along with the mechanism of
      antigen recognition. This chapter also describes the disorders of immune system
      in brief. 

PMID- 25048115
TI  - Principles of calcite dissolution in human and artificial otoconia.
AB  - Human otoconia provide mechanical stimuli to deflect hair cells of the vestibular
      sensory epithelium for purposes of detecting linear acceleration and head tilts.
      During lifetime, the volume and number of otoconia are gradually reduced. In a
      process of degeneration morphological changes occur. Structural changes in human
      otoconia are assumed to cause vertigo and balance disorders such as benign
      paroxysmal positional vertigo (BPPV). The aim of this study was to investigate
      the main principles of morphological changes in human otoconia in dissolution
      experiments by exposure to hydrochloric acid, EDTA, demineralized water and
      completely purified water respectively. For comparison reasons artificial
      (biomimetic) otoconia (calcite gelatin nanocomposits) and natural calcite were
      used. Morphological changes were detected in time steps by the use of
      environmental scanning electron microscopy (ESEM). Under in vitro conditions
      three main dissolution mechanisms were identified as causing characteristic
      morphological changes of the specimen under consideration: pH drops in the acidic
      range, complex formation with calcium ions and changes of ion concentrations in
      the vicinity of otoconia. Shifts in pH cause a more uniform reduction of otoconia
      size (isotropic dissolution) whereas complexation reactions and changes of the
      ionic concentrations within the surrounding medium bring about preferred attacks
      at specific areas (anisotropic dissolution) of human and artificial otoconia.
      Owing to successive reduction of material, all the dissolution mechanisms finally
      produce fragments and remnants of otoconia. It can be assumed that the organic
      component of otoconia is not significantly attacked under the given conditions.
      Artificial otoconia serve as a suitable model system mimicking chemical attacks
      on biogenic specimens. The underlying principles of calcite dissolution under in
      vitro conditions may play a role in otoconia degeneration processes such as BPPV.

PMID- 25048117
TI  - Cross talk between the metabolic and immune systems.
AB  - Understanding the interplay between metabolic and cellular signaling systems has
      emerged as a focus in the study of metabolic disorders, cancer, and immune
      responses. Immune system is active in the regulation of metabolism. Lymphocyte
      activation initiates a program of cell growth, proliferation, and differentiation
      that increase metabolic demand. Activated lymphocytes must alter their metabolism
      to support these increased synthetic activities. In this chapter, we describe how
      signaling via the immune system integrates with metabolic functions to control
      immune response and vice versa. It has been explained mainly in the context of T
      lymphocyte activation and, to a lesser detail, in other immune cell types. 

PMID- 25048118
TI  - Immunoinformatics: a brief review.
AB  - A large volume of data relevant to immunology research has accumulated due to
      sequencing of genomes of the human and other model organisms. At the same time,
      huge amounts of clinical and epidemiologic data are being deposited in various
      scientific literature and clinical records. This accumulation of the information
      is like a goldmine for researchers looking for mechanisms of immune function and
      disease pathogenesis. Thus the need to handle this rapidly growing immunological
      resource has given rise to the field known as immunoinformatics.
      Immunoinformatics, otherwise known as computational immunology, is the interface
      between computer science and experimental immunology. It represents the use of
      computational methods and resources for the understanding of immunological
      information. It not only helps in dealing with huge amount of data but also plays
      a great role in defining new hypotheses related to immune responses. This chapter
      reviews classical immunology, different databases, and prediction tool. Further,
      it briefly describes applications of immunoinformatics in reverse vaccinology,
      immune system modeling, and cancer diagnosis and therapy. It also explores the
      idea of integrating immunoinformatics with systems biology for the development of
      personalized medicine. All these efforts save time and cost to a great extent. 

PMID- 25048119
TI  - Immunoinformatics of the V, C, and G domains: IMGT(r) definitive system for IG,
      TR and IgSF, MH, and MhSF.
AB  - By its creation in 1989, IMGT((r)), the international ImMunoGeneTics information
      system((r)) ( http://www.imgt.org , CNRS and Universite Montpellier 2), marked
      the advent of immunoinformatics, which emerged at the interface between
      immunogenetics and bioinformatics. IMGT((r)) is the global reference in
      immunogenetics and immunoinformatics. The accuracy and the consistency of the
      IMGT((r)) data are based on the IMGT Scientific chart rules generated from the
      IMGT-ONTOLOGY axioms and concepts, which comprise IMGT standardized labels
      (DESCRIPTION), IMGT gene and allele nomenclature (CLASSIFICATION), IMGT unique
      numbering, and IMGT Collier de Perles (NUMEROTATION). The IMGT((r)) standards
      have bridged the gap between genes, sequences, and three-dimensional (3D)
      structures for the receptors, chains, and domains. Started specifically for the
      immunoglobulins (IG) or antibodies and T cell receptors (TR), the IMGT-ONTOLOGY
      concepts have been extended to conventional genes of the immunoglobulin
      superfamily (IgSF) and major histocompatibility (MH) superfamily (MhSF), members
      of which are defined by the presence of at least one variable (V) or constant (C)
      domain, or two groove (G) domains, respectively. In this chapter, we review the
      IMGT((r)) definitive system for the V, C, and G domains, based on the IMGT
      ONTOLOGY concepts of IMGT unique numbering and IMGT Collier de Perles. 

PMID- 25048120
TI  - IMGT/HLA and the Immuno Polymorphism Database.
AB  - The IMGT/HLA Database (http://www.ebi.ac.uk/ipd/imgt/hla/) was first released
      over 15 years ago, providing the HLA community with a searchable repository of
      highly curated HLA sequences. The HLA complex is located within the 6p21.3 region
      of human chromosome 6 and contains more than 220 genes of diverse function. Many
      of the genes encode proteins of the immune system and are highly polymorphic,
      with some genes currently having over 3,000 known allelic variants. The Immuno
      Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) expands on this model,
      with a further set of specialist databases related to the study of polymorphic
      genes in the immune system. The IPD project works with specialist groups or
      nomenclature committees who provide and curate individual sections before they
      are submitted to IPD for online publication. IPD currently consists of four
      databases: IPD-KIR contains the allelic sequences of killer-cell immunoglobulin
      like receptors; IPD-MHC is a database of sequences of the major
      histocompatibility complex of different species; IPD-HPA, alloantigens expressed
      only on platelets; and IPD-ESTDAB, which provides access to the European
      Searchable Tumour Cell-Line Database, a cell bank of immunologically
      characterized melanoma cell lines. Through the work of the HLA Informatics Group
      and in collaboration with the European Bioinformatics Institute we are able to
      provide public access to this data through the website http://www.ebi.ac.uk/ipd/.

PMID- 25048121
TI  - Databases for T-cell epitopes.
AB  - Modem immunology and vaccinology incorporate immunoinformatics techniques to give
      insights into immune systems and accelerate vaccine design. Databases managing
      epitope data in a structured form with immune-related annotations including
      sequences, alleles, source organisms, structures, and diseases could be the most
      crucial part of immunoinformatics offering data sources for the analysis of
      immune systems and development of prediction methods. This chapter provides an
      overview of publicly available databases of T-cell epitopes including general
      databases, pathogen- and tumor-specific databases, and 3D structure databases. 

PMID- 25048122
TI  - Databases for B-cell epitopes.
AB  - Identification and characterization of B-cell epitopes in target antigens is one
      of the key steps in epitope-driven vaccine design, immunodiagnostic tests, and
      antibody production. For localizing epitopes by experimental methods is time
      consuming and cost expensive, researchers have been developing in silico or
      computational models for the prediction of B-cell epitopes, enabling
      immunologists and clinicians to identify the most promising epitopes for
      characterization in the laboratory. A sufficient number of available B-cell
      epitopes are indispensable for establishing the prediction models. To our
      knowledge, some popular databases associated with the B-cell epitopes are
      proposed and widely used in the immunoinformatics. In this chapter, we present an
      overview of the important databases and introduce how to compile datasets for the
      development of B-cell epitope prediction tools. 

PMID- 25048123
TI  - Antigen-Antibody Interaction Database (AgAbDb): a compendium of antigen-antibody
      interactions.
AB  - Antigen-Antibody Interaction Database (AgAbDb) is an immunoinformatics resource
      developed at the Bioinformatics Centre, University of Pune, and is available
      online at http://bioinfo.net.in/AgAbDb.htm. Antigen-antibody interactions are a
      special class of protein-protein interactions that are characterized by high
      affinity and strict specificity of antibodies towards their antigens. Several co
      crystal structures of antigen-antibody complexes have been solved and are
      available in the Protein Data Bank (PDB). AgAbDb is a derived knowledgebase
      developed with an objective to compile, curate, and analyze determinants of
      interactions between the respective antigen-antibody molecules. AgAbDb lists not
      only the residues of binding sites of antigens and antibodies, but also
      interacting residue pairs. It also helps in the identification of interacting
      residues and buried residues that constitute antibody-binding sites of protein
      and peptide antigens. The Antigen-Antibody Interaction Finder (AAIF), a program
      developed in-house, is used to compile the molecular interactions, viz. van der
      Waals interactions, salt bridges, and hydrogen bonds. A module for curating water
      mediated interactions has also been developed. In addition, various residue-level
      features, viz. accessible surface area, data on epitope segment, and secondary
      structural state of binding site residues, are also compiled. Apart from the PDB
      numbering, Wu-Kabat numbering and explicit definitions of complementarity
      determining regions are provided for residues of antibodies. The molecular
      interactions can be visualized using the program Jmol. AgAbDb can be used as a
      benchmark dataset to validate algorithms for prediction of B-cell epitopes. It
      can as well be used to improve accuracy of existing algorithms and to design new
      algorithms. AgAbDb can also be used to design mimotopes representing antigens as
      well as aid in designing processes leading to humanization of antibodies.

PMID- 25048124
TI  - Allergen databases.
AB  - In this chapter, five popular allergen databases have been described: (1)
      Allergome is based on basic and clinical information on allergens causing an IgE
      mediated disease; (2) AllergenOnline allows online search of peer-reviewed
      allergen list; (3) International Union of Immunological Societies Allergen
      nomenclature subcommittee database contains systematic nomenclature and molecular
      details of well-characterized allergens; (4) AllFam allows classifying allergens
      into protein families based on domain information; and (5) SDAP provides in
      detail structural information of the allergens. 

PMID- 25048125
TI  - Prediction of conformational B-cell epitopes.
AB  - Conformational B-cell epitopes play an important role in the epitope-based
      vaccine design. The increase of available data promotes the development of
      computational methods. Compared with the wet experiments, the computational
      methods are faster and more economic. In the past few years, a number of
      computational methods (especially the machine learning-based methods) have been
      developed to predict the conformational B-cell epitopes. In this chapter, we
      introduce important data resources and computational methods, which are publicly
      available. Moreover, we introduce our ensemble learning-based method that can
      predict the conformational epitopes from sequences. These promising methods may
      assist immunologists in identifying potential vaccine candidates. 

PMID- 25048126
TI  - Computational prediction of B cell epitopes from antigen sequences.
AB  - Computational identification of B-cell epitopes from antigen chains is a
      difficult and actively pursued research topic. Efforts towards the development of
      method for the prediction of linear epitopes span over the last three decades,
      while only recently several predictors of conformational epitopes were released.
      We review a comprehensive set of 13 recent approaches that predict linear and 4
      methods that predict conformational B-cell epitopes from the antigen sequences.
      We introduce several databases of B-cell epitopes, since the availability of the
      corresponding data is at the heart of the development and validation of
      computational predictors. We also offer practical insights concerning the use and
      availability of these B-cell epitope predictors, and motivate and discuss feature
      research in this area. 

PMID- 25048127
TI  - Machine learning-based methods for prediction of linear B-cell epitopes.
AB  - B-cell epitope prediction facilitates immunologists in designing peptide-based
      vaccine, diagnostic test, disease prevention, treatment, and antibody production.
      In comparison with T-cell epitope prediction, the performance of variable length
      B-cell epitope prediction is still yet to be satisfied. Fortunately, due to
      increasingly available verified epitope databases, bioinformaticians could adopt
      machine learning-based algorithms on all curated data to design an improved
      prediction tool for biomedical researchers. Here, we have reviewed related
      epitope prediction papers, especially those for linear B-cell epitope prediction.
      It should be noticed that a combination of selected propensity scales and
      statistics of epitope residues with machine learning-based tools formulated a
      general way for constructing linear B-cell epitope prediction systems. It is also
      observed from most of the comparison results that the kernel method of support
      vector machine (SVM) classifier outperformed other machine learning-based
      approaches. Hence, in this chapter, except reviewing recently published papers,
      we have introduced the fundamentals of B-cell epitope and SVM techniques. In
      addition, an example of linear B-cell prediction system based on physicochemical
      features and amino acid combinations is illustrated in details. 

PMID- 25048128
TI  - Mimotope-based prediction of B-cell epitopes.
AB  - Mimotopes are peptides mimicking epitopes on the corresponding antigen. They can
      be obtained via panning the phage-displayed random peptide library against the
      corresponding monoclonal antibody or specific sera. Besides mimotopes however,
      the experimental results also include all kinds of unwanted sequences called
      "target-unrelated peptides," which often interfere with the subsequent
      experimental and computational analyses. Nevertheless, the prediction of B-cell
      epitopes based on the experimental result of phage display has shown to be a
      promising and reliable strategy with acceptable precision. In this chapter, we
      summarize mimotope-based prediction of B-cell epitopes under three conditions and
      focus on protocols and tips for retrieving, cleaning, and decoding the data from
      phage display technology. 

PMID- 25048129
TI  - Hybrid methods for B-cell epitope prediction.
AB  - Many computational approaches to B-cell epitope prediction have been published,
      including combinations of previously proposed methods, which complicates the
      tasks of further developing such computational approaches and of selecting those
      most appropriate for practical applications (e.g., the design of novel
      immunodiagnostics and vaccines). These tasks are considered together herein to
      clarify their close but often overlooked interrelationship, thereby providing a
      guide to their performance in mutual support of one another, with emphasis on key
      physicochemical and biological considerations that are relevant from an
      applications perspective. This aims to assist investigators in performing either
      or both tasks, with the overall goals of successfully applying computational
      tools towards practical ends and of generating informative new data towards
      iterative improvement of the tools, particularly as regards the design of peptide
      based immunogens for eliciting the production of antipeptide antibodies that
      modulate biological activity of protein targets via functionally relevant cross
      reactivity in relation to the phenomena of protein folding and protein disorder. 

PMID- 25048130
TI  - Building classifier ensembles for B-cell epitope prediction.
AB  - Identification of B-cell epitopes in target antigens is a critical step in
      epitope-driven vaccine design, immunodiagnostic tests, and antibody production. B
      cell epitopes could be linear, i.e., a contiguous amino acid sequence fragment of
      an antigen, or conformational, i.e., amino acids that are often not contiguous in
      the primary sequence but appear in close proximity within the folded 3D antigen
      structure. Numerous computational methods have been proposed for predicting both
      types of B-cell epitopes. However, the development of tools for reliably
      predicting B-cell epitopes remains a major challenge in
      immunoinformatics.Classifier ensembles a promising approach for combining a set
      of classifiers such that the overall performance of the resulting ensemble is
      better than the predictive performance of the best individual classifier. In this
      chapter, we show how to build a classifier ensemble for improved prediction of
      linear B-cell epitopes. The method can be easily adapted to build classifier
      ensembles for predicting conformational epitopes. 

PMID- 25048131
TI  - Multiplex peptide-based B cell epitope mapping.
AB  - B cell epitope mapping is widely applied to determine antibody-binding sites.
      Several methods exist to map B cell epitopes and here we describe three methods
      that are characterized by the simultaneous analysis of multiple peptides. In the
      first approach a microarray of overlapping synthetic peptides derived from an
      antigenic protein is used and the binding of the antibodies is analyzed by
      fluorescently labeled secondary antibodies. This method is particularly suited
      for the identification of linear epitopes of an established target protein. In
      the second approach the binding of antibodies to a random synthetic peptide
      library immobilized on microbeads is determined by enzyme-conjugated secondary
      antibodies and the selection of antibody-bound beads by a light microscope. This
      method can be applied when information on the identity of the antigenic protein
      is lacking. In the third method an antigen is proteolytically digested and
      antibody binding to the resulting peptides is analyzed by surface plasmon
      resonance imaging (iSPR). The latter method can be applied when the purified
      antigenic protein is available. 

PMID- 25048132
TI  - Classification of human leukocyte antigen (HLA) supertypes.
AB  - Identification of new antigenic peptides, derived from infectious agents or
      cancer cells, which bind to human leukocyte antigen (HLA) class I and II
      molecules, is of importance for the development of new effective vaccines capable
      of activating the cellular arm of the immune response. However, the barrier to
      the development of peptide-based vaccines with maximum population coverage is
      that the restricting HLA genes are extremely polymorphic resulting in a vast
      diversity of peptide-binding HLA specificities and a low population coverage for
      any given peptide-HLA specificity. One way to reduce this complexity is to group
      thousands of different HLA molecules into several so-called HLA supertypes: a
      classification that refers to a group of HLA alleles with largely overlapping
      peptide binding specificities. In this chapter, we focus on the state-of-the-art
      classification of HLA supertypes including HLA-I supertypes and HLA-II supertypes
      and their application in development of peptide-based vaccines. 

PMID- 25048133
TI  - Customized predictions of peptide-MHC binding and T-cell epitopes using EPIMHC.
AB  - Peptide binding to major histocompatibility complex (MHC) molecules is the most
      selective requisite for T-cell recognition. Therefore, prediction of peptide-MHC
      binding is the main basis for anticipating T-cell epitopes. A very popular and
      accurate method to predict peptide-MHC binding is based on motif-profiles and
      here we show how to make them using EPIMHC (http://imed.med.ucm.es/epimhc/).
      EPIMHC is a database of T-cell epitopes and MHC-binding peptides that unlike any
      related resource provides a framework for computational vaccinology. In this
      chapter, we describe how to derive peptide-MHC binding motif-profiles in EPIMHC
      and use them to predict peptide-MHC binding and T-cell epitopes. Moreover, we
      show evidence that customization of peptide-MHC binding predictors can lead to
      enhanced epitope predictions.

PMID- 25048134
TI  - T-cell epitope prediction methods: an overview.
AB  - The scientific community is overwhelmed by the voluminous increase in the quantum
      of data on biological systems, including but not limited to the immune system.
      Consequently, immunoinformatics databases are continually being developed to
      accommodate this ever increasing data and analytical tools are continually being
      developed to analyze the same. Therefore, researchers are now equipped with
      numerous databases, analytical and prediction tools, in anticipation of better
      means of prevention of and therapeutic intervention in diseases of humans and
      other animals. Epitope is a part of an antigen, recognized either by B- or T
      cells and/or molecules of the host immune system. Since only a few amino acid
      residues that comprise an epitope (instead of the whole protein) are sufficient
      to elicit an immune response, attempts are being made to identify or predict this
      critical stretch or patch of amino acid residues, i.e., T-cell epitopes and B
      cell epitopes to be included in multiple-subunit vaccines. T-cell epitope
      prediction is a challenge owing to the high degree of MHC polymorphism and
      disparity in the volume of data on various steps encountered in the generation
      and presentation of T-cell epitopes in the living systems. Many
      algorithms/methods developed to predict T-cell epitopes and Web servers
      incorporating the same are available. These are based on approaches like
      considering amphipathicity profiles of proteins, sequence motifs, quantitative
      matrices (QM), artificial neural networks (ANN), support vector machines (SVM),
      quantitative structure activity relationship (QSAR) and molecular docking
      simulations, etc. This chapter aims to introduce the reader to the principle(s)
      underlying some of these methods/algorithms as well as procedural and practical
      aspects of using the same.

PMID- 25048135
TI  - Computational antigenic epitope prediction by calculating electrostatic
      desolvation penalties of protein surfaces.
AB  - The prediction of antigenic epitopes on the surface of proteins is of great
      importance for vaccine development and to specifically design recombinant
      antibodies. Computational methods based on the three-dimensional structure of the
      protein allow for the detection of noncontinuous epitopes in contrast to methods
      based on the primary amino-acid sequence only. A method recently developed to
      predict protein-protein binding sites is presented, and the application to
      predict putative antigenic epitopes is described in detail. The prediction
      approach is based on the local perturbation of the electrostatic field at the
      surface of a protein due to a neutral probe of low dielectric constant that
      represents an approaching binding partner. The calculated change in electrostatic
      energy corresponds to an energy penalty of desolvating a protein surface region,
      and antigenic epitope surface regions tend to be associated with a lower penalty
      compared to the average protein surface. The protocol to perform the calculations
      is described and illustrated on an example antigen, the outer surface protein A
      of Borrelia burgdorferi, a pathogenic organism causing lyme disease. 

PMID- 25048136
TI  - In silico prediction of allergenic proteins.
AB  - Currently, the prediction of new allergens is becoming important due to use of
      genetically modified (GM) foods and biopharmaceuticals. In this chapter, we
      describe how to use four popular allergenic prediction servers: (1) Structural
      Database of Allergenic Proteins (SDAP), (2) Allermatch, (3) Evaller 2, and (4)
      AlgPred. The first two prediction servers are based on traditional approaches,
      whereas Evaller 2 and AlgPred use sophisticated machine learning techniques. 

PMID- 25048137
TI  - Prediction of virulence factors using bioinformatics approaches.
AB  - Virulence factors produced by a pathogen are essential for causing disease in the
      host. They enable the pathogen to establish itself within the host thus enhancing
      its potential to cause disease and in some instances underlie evasion of host
      defense mechanisms. Identification of these molecules, especially those of
      immunological interest and their use in vaccine development are attractive and
      are among the initial steps of reverse vaccinology. Surface localized virulence
      factors such as adhesins serve as excellent immunogenic candidates in this
      regard. In this chapter we have described the bioinformatics approaches for
      adhesin prediction, which include specific adhesin prediction algorithms. 

PMID- 25048138
TI  - A systems biology approach to study systemic inflammation.
AB  - Systemic inflammation needs a precise control on the sequence and magnitude of
      occurring events. The high throughput data on the host-pathogen interactions
      gives us an opportunity to have a glimpse on the systemic inflammation. In this
      article, a dynamic Candida albicans-zebrafish interactive infectious network is
      built as an example to demonstrate how systems biology approach can be used to
      study systematic inflammation. In particular, based on microarray data of C.
      albicans and zebrafish during infection, the hyphal growth, zebrafish, and host
      pathogen intercellular PPI networks were combined to form an integrated
      infectious PPI network that helps us understand the systematic mechanisms
      underlying the pathogenicity of C. albicans and the immune response of the host.
      The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2
      significant interactions found in the intercellular PPI network. Two cellular
      networks were also developed corresponding to the different infection stages
      (adhesion and invasion), and then compared with each other to identify proteins
      to gain more insight into the pathogenic role of hyphal development in the C.
      albicans infection process. Important defense-related proteins in zebrafish were
      predicted using the same approach. This integrated network consisting of
      intercellular invasion and cellular defense processes during infection can
      improve medical therapies and facilitate development of new antifungal drugs. 

PMID- 25048139
TI  - Procedures for mucosal immunization and analyses of cellular immune response to
      candidate HIV vaccines in murine and nonhuman primate models.
AB  - Sampling the mucosal tissues and analyses of immune responses are integral to
      vaccine-development strategies against human immunodeficiency virus (HIV), which
      is transmitted predominantly across the oro-genital mucosa. While immune assay
      development and standardization attempts employ mouse models, immunogenicity and
      protective efficacy that can be extrapolated to humans are realized only from
      experiments in nonhuman primates. Here, we describe commonly used practices for
      immunizations in rhesus macaques (Macaca mulatta) along with procedures for
      obtaining important mucosal tissues samples from macaques and mice. We also
      describe detailed protocols for two important assays applicable in mouse as well
      as primate experiments for determining antigen-specific T cells responses induced
      after vaccination. 

PMID- 25048140
TI  - Immunoinformatics and systems biology in personalized medicine.
AB  - Every year new databases and tools for the storage and analysis of biological
      data are developed, updated, and discontinued. For this reason it is very
      important to have a clear picture of the major repositories providing information
      about the availability of these databases and tools as well as a brief
      description of them. This chapter provides an overview of the most important
      information sources which can guide researchers through the process of selecting
      databases and tools of interest for immunoinformatics and systems biology in
      personalized medicine. As an example of a particular resource of interest that
      combines a curated database and tools for data analysis, this chapter also
      includes a description of InnateDB. This database offers access to curated
      information relative to the innate immune response in a systems biology context.

PMID- 25048141
TI  - The role of small RNAs in vaccination.
AB  - The concept of vaccination came to light following Edward Jenner's classical
      observation on milkmaids who were protected against smallpox. However, plants
      lack the cellular based immunity system and thus it was not appreciated earlier
      that plants can also be protected from their pathogens. But phenomena like cross
      protection, pathogen derived resistance (PDR), viral recovery, etc. in plants
      suggested that plants have also evolved immunity against their pathogens. The
      further advances in the field revealed that an endogenous defense system could
      have multiple prongs. With the advent of RNAi, it was clear that the antiviral
      immune responses are related to the induction of specific small RNAs. The
      detection of virus specific small RNAs (vsiRNA) in immunized plants confirmed
      their roles in the immunity against pathogens. Although many issues related to
      antiviral mechanisms are yet to be addressed, the existing tools of RNAi can be
      efficiently used to control the invading viruses in transgenic plants. It is also
      possible that the microRNA(s) induced in infected plants impart immunity against
      viral pathogens. So the small RNA molecules play a vital role in defense system
      and these can be engineered to enhance the immunity against specific viral
      pathogens. 

PMID- 25048143
TI  - Immunoinformatics, molecular modeling, and cancer vaccines.
AB  - Cancer vaccines are a natural way of fighting the development and progression of
      cancer as they harness the power of immune system to tweak it into killing
      cancerous cells. One of the most important agents in an immune system, the
      cytotoxic T cells (CTL), play a major role and the CTL epitopes in the form of an
      immunotherapeutic product have been shown to help mount an immune response
      towards tumor cell destruction. Immunoinformatics and molecular modeling tools
      have proven powerful towards the prediction of plausible CTL epitopes as well as
      other epitopes, cutting short the time and cost. We focus on the sequential
      methodology using these tools as well as some databases to generate a succinct
      list of enterprising subtype-specific or promiscuous peptide epitopes. 

PMID- 25048142
TI  - Structure-based clustering of major histocompatibility complex (MHC) proteins for
      broad-based T-cell vaccine design.
AB  - Structure-based clustering technique is useful for identifying superfamilies of
      major histocompatibility complex (MHC) proteins with similar binding
      specificities. The resolved MHC superfamilies play an important role in vaccine
      development, from discovering new targets for broad-based vaccines and
      therapeutics to optimizing the affinity and selectivity of hits. Here, we
      describe a protocol and provide a summary for grouping MHC proteins according to
      their structural interaction characteristics. 

PMID- 25048145
TI  - Mathematical models of HIV replication and pathogenesis.
AB  - This review outlines how mathematical models have been helpful, and continue to
      be so, for obtaining insights into the in vivo dynamics of HIV infection. The
      review starts with a discussion of a basic mathematical model that has been
      frequently used to study HIV dynamics. Some crucial results are described,
      including the estimation of key parameters that characterize the infection, and
      the generation of influential theories which argued that in vivo virus evolution
      is a key player in HIV pathogenesis. Subsequently, more recent concepts are
      reviewed that have relevance for disease progression, including the multiple
      infection of cells and the direct cell-to-cell transmission of the virus through
      the formation of virological synapses. These are important mechanisms that can
      influence the rate at which HIV spreads through its target cell population, which
      is tightly linked to the rate at which the disease progresses towards AIDS. 

PMID- 25048144
TI  - Investigating host-pathogen behavior and their interaction using genome-scale
      metabolic network models.
AB  - Genome Scale Metabolic Modeling methods represent one way to compute whole cell
      function starting from the genome sequence of an organism and contribute towards
      understanding and predicting the genotype-phenotype relationship. About 80 models
      spanning all the kingdoms of life from archaea to eukaryotes have been built till
      date and used to interrogate cell phenotype under varying conditions. These
      models have been used to not only understand the flux distribution in
      evolutionary conserved pathways like glycolysis and the Krebs cycle but also in
      applications ranging from value added product formation in Escherichia coli to
      predicting inborn errors of Homo sapiens metabolism. This chapter describes a
      protocol that delineates the process of genome scale metabolic modeling for
      analysing host-pathogen behavior and interaction using flux balance analysis
      (FBA). The steps discussed in the process include (1) reconstruction of a
      metabolic network from the genome sequence, (2) its representation in a precise
      mathematical framework, (3) its translation to a model, and (4) the analysis
      using linear algebra and optimization. The methods for biological interpretations
      of computed cell phenotypes in the context of individual host and pathogen models
      and their integration are also discussed. 

PMID- 25048146
TI  - Intraamygdaloid microinjection of RFamide-related peptide-3 decreases food intake
      in rats.
AB  - Some members of the RFamide peptide family are associated with feeding in
      rodents. For example, neuropeptide FF and prolactin-releasing peptide cause
      anorexigenic, while 26RFa and QRFP result in orexigenic effects. I.c.v.
      microinjection of RFamide-related peptide-3 (RFRP-3) facilitates feeding. Feeding
      related effects of RFRP-3, however, have not been studied after direct brain
      microinjections in rats. The central part of amygdala (CeA) is essentially
      involved in the regulation of feeding and body weight. RFRP-3 positive nerve
      cells were detected in the rat hypothalamus and RFRP-3 immunoreactive fibers were
      identified in the CeA. RFRP analogs bind with relatively high affinity to the
      NPFF1 and NPFF2 receptors (NPFF-R). RFRP-3 has potent activity for NPFF-1 that is
      expressed in the CeA. To evaluate the role of RFRP-3 in feeding regulation rats
      were microinjected with different doses of RFRP-3 and their food intake were
      quantified over a 60 min period. Liquid food intake of male Wistar rats was
      measured after bilateral intraamygdalar administration of RFRP-3 (25, 50, 100 or
      200 ng/side, RFRP-3 dissolved in 0.15M sterile NaCl/0.4 MUl, respectively). The
      50 ng and 100 ng doses of RFRP-3 microinjections resulted in significant decrease
      of food intake. Twenty-five and 200 ng had no effect. Food intake decreasing
      effect of RFRP-3 was eliminated by NPFF-R antagonist RF9 pretreatment. In open
      field test effective doses of RFRP-3 did not modify spontaneous locomotor
      activity and general behavior of animals did not change. Our results are the
      first reporting that RFRP-3 injected to the CeA resulted in a decrease of liquid
      food consumption. This is a receptor-linked effect because it was eliminated by
      NPFF-R antagonist.

PMID- 25048148
TI  - Colorectal cancer outcome inequalities: association between population density,
      race, and socioeconomic status.
AB  - INTRODUCTION: Conflicting data exists regarding the influence of population
      density on colorectal cancer (CRC) outcomes; to better understand this, the
      present study evaluated outcomes along an urban-rural continuum. METHODS:
      Colorectal patients aged &#8805;40 years from 1992 to 2002 were identified in the
      SEER (Surveillance, Epidemiology, and End Results) Registries of the National
      Cancer Institute in the USA. RESULTS: A total of 176 011 patients were
      identified, with median age 71; most lived in populous counties and were white
      (90%). Patients from large metropolitan counties were more often African
      American, and those in rural counties were more likely to be white and have low
      socioeconomic status (SES). Patients from large metropolitan (>1 million) and
      rural counties were more likely to have metastatic disease and decreased survival
      compared to smaller metropolitan counties (<1 million). Late stage of
      presentation and diminished survival were also associated with African-American
      race, male sex and lower SES. CONCLUSIONS: Metropolitan counties with populations
      <1 million had superior CRC outcomes, in part secondary to race and SES.

PMID- 25048147
TI  - Lean forward: Genetic analysis of temperature-sensitive mutants unfolds the
      secrets of oligomeric protein complex assembly.
AB  - Multisubunit protein complexes are essential for cellular function. Genetic
      analysis of essential processes requires special tools, among which temperature
      sensitive (Ts) mutants have historically been crucial. Many researchers assume
      that the effect of temperature on such mutants is to drive their proteolytic
      destruction. In fact, degradation-mediated elimination of mutant proteins likely
      explains only a fraction of the phenotypes associated with Ts mutants. Here I
      discuss insights gained from analysis of Ts mutants in oligomeric proteins, with
      particular focus on the study of septins, GTP-binding subunits of cytoskeletal
      filaments whose structures and functions are the subject of current investigation
      in my and many other labs. I argue that the kinds of unbiased forward genetic
      approaches that generate Ts mutants provide information that is largely
      inaccessible to modern reverse genetic methodologies, and will continue to drive
      our understanding of higher-order assembly by septins and other oligomeric
      proteins. 

PMID- 25048149
TI  - On the classification of diseases.
AB  - Identifying the necessary and sufficient conditions for individuating and
      classifying diseases is a matter of great importance in the fields of law,
      ethics, epidemiology, and of course, medicine. In this paper, I first propose a
      means of achieving this goal, ensuring that no two distinct disease-types could
      correctly be ascribed to the same disease-token. I then posit a metaphysical
      ontology of diseases-that is, I give an account of what a disease is. This is
      essential to providing the most effective means of interfering with disease
      processes. Following existing work in the philosophy of medicine and epidemiology
      (primarily Christopher Boorse; Caroline Whitbeck; Alexander Broadbent),
      philosophy of biology (Joseph LaPorte; D.L. Hull), conditional analyses of
      causation (J.L. Mackie; David Lewis), and recent literature on dispositional
      essentialism (Stephen Mumford and Rani Anjum; Alexander Bird), I endorse a
      dispositional conception of disease. Following discussion of various conceptions
      of disease-identity, their relations to the clinical and pathological effects of
      the diseases in question, and how diseases are treated, I conclude (i) that
      diseases should be individuated by their causes, and (ii) that diseases are
      causal processes best seen as simultaneously acting sequences of mutually
      manifesting dispositions. 

PMID- 25048150
TI  - Evaluating the results of stress urinary incontinence surgery with objective and
      subjective outcome measures.
AB  - OBJECTIVE: To assess the outcomes of stress urinary incontinence (SUI) surgery
      using objective and subjective measures in women with pure SUI and mixed urinary
      incontinence (MUI). The degree of correlation between the different outcome
      measures was also evaluated for both groups. STUDY DESIGN: A multicentre
      prospective cohort study of women who underwent surgery for SUI. A standardized
      cough stress test was used as the objective outcome measure, and specific items
      of the Epidemiology of Prolapse and Incontinence Questionnaire were used as the
      subjective outcome measure. The International Consultation on Incontinence
      Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Patient Global
      Impression of Improvement (PGI-I) questionnaires were used for global assessment.
      Kappa test was used to measure the degree of correlation between the outcome
      measures. RESULTS: The participants were categorized into two groups before
      surgery: pure SUI (n=116) and MUI (n=161). Six months after surgery, the cure
      rate of the SUI component was high in both groups according to the objective and
      subjective outcome measures. Global assessment showed lower cure rates. The
      degree of agreement between objective and subjective outcome measures was
      moderate (kappa 0.541, p<0.001) for women with pure SUI, and fair (kappa 0.377,
      p<0.001) for women with MUI. Correlation between the change in ICIQ-UI SF score
      (pre to post surgery) and the degree of satisfaction (PGI-I) was significant
      (p<0.01) for both the pure SUI group (0.43) and the MUI group (0.48).
      CONCLUSIONS: Both objective and subjective cure rates are high for women with
      pure SUI and MUI following SUI surgery in Spain. The degree of agreement between
      different outcome measures varies.

PMID- 25048151
TI  - Ultra-high-risk pregnancies in women after renal transplantation.
AB  - OBJECTIVES: This study evaluates pregnancy outcomes in renal transplant
      recipients who have additional obstetrical, surgical, or urological risk factors.
      STUDY DESIGN: Data from our transplantation and obstetrical databases were
      retrospectively analyzed to identify all women of reproductive age who had
      undergone renal transplantation between 1999 and 2013 at our tertiary referral
      center and had subsequently become pregnant. Characteristics of pregnancy and
      perinatal outcome parameters; obstetrical, urological, and surgical risk factors;
      and graft function were assessed. Descriptive data analysis, Fisher's exact test,
      unpaired Student's t-test and one-way analysis of the variance were performed.
      RESULTS: The overall pregnancy rate after renal transplantation was 5% (n=13).
      77% of the patients (n=10) had ultra-high-risk pregnancies due to additional risk
      factors. These included twin pregnancy, placenta previa/percreta, hypertension;
      previous heart transplantation, previous myocardial infarction; postoperative
      lymphocele, urinary leakage, hydronephrosis, or vesico-ureteral reflux. Two
      patients had two consecutive pregnancies. A total of 12 deliveries with 13
      newborns were achieved. Cesarean section and preterm delivery rates were 67% and
      50%, respectively. Mean gestational week at delivery was 36 +/- 3. Mean
      creatinine levels were higher in women with preterm deliveries and in those of
      advanced age. Mean time between transplantation and delivery was 79 +/- 36
      months. All patients had adequate graft function after a mean follow-up of 128 +/
      50 months after renal transplantation. CONCLUSIONS: Pregnant women after renal
      transplantation commonly present with additional risk factors. In these ultra
      high-risk pregnancies successful outcomes can be achieved in a multidisciplinary
      setting. Adequate graft function and urinary tract evaluation is necessary.

PMID- 25048152
TI  - A gene variant in the transcription factor 7-like 2 (TCF7L2) is associated with
      an increased risk of gestational diabetes mellitus.
AB  - OBJECTIVE: Adipokines play an important role in the pathogenesis of insulin
      resistance during pregnancy. We studied the association of genetic variants
      linked with type 2 diabetes in gestational diabetes mellitus (GDM) subjects and
      its influence on maternal adipokines. STUDY DESIGN: We recruited 25 healthy
      pregnant women (Controls) and 45 women with GDM at 24-28 weeks of gestation.
      Maternal blood samples were collected at recruitment and delivery. Adipokines
      were determined at both sampling times. Genomic DNA was extracted from
      recruitment samples and FTO rs9939609, TCF7L2 rs4506565, rs7901695, rs12243326,
      rs12255372 and rs7903146, INSIG2 rs7566605, SREBF1 rs114001633, rs45535737 and
      rs12941356 and FATP4 rs2003560 genotyped. RESULTS: Serum adiponectin was
      significantly lower in GDM than Controls at recruitment and showed a similar
      trend at delivery (p=0.060). In contrast, resistin tended to higher levels in GDM
      only at recruitment. TCF7L2 rs4506565 (OR=2.31, 95% CI: 1.97-5.01; p=0.031) and
      FTO rs9939609 (OR=2.17, 95% CI: 1.07-4.41; p=0.039) were associated with GDM
      risk. Women carrying the T allele of TCF7L2 rs4506565 had increases in plasma
      resistin of 9.38 MUg/L (95% CI 1.39-17.37; p=0.022) per allele; this association
      remained significant after adjusting for pre-gestational body weight. CONCLUSION:
      TCF7L2 rs4506565 variant (T/T) is associated with increased risk of GDM and
      plasma resistin concentrations in women with GDM.

PMID- 25048153
TI  - Additive effect of autologous platelet concentrates in treatment of intrabony
      defects: a systematic review and meta-analysis.
AB  - The aim of the present review is to systematically evaluate the additive effect
      of autologous platelet concentrates (APCs) in treatment of intrabony defects when
      used along with other regenerative procedures and when used alone in terms of
      clinical and radiological outcomes. A search was performed in electronic
      databases (i.e., MEDLINE and the Cochrane Central Register of Controlled Trials)
      in order to identify randomized clinical trials (RCTs) assessing the additive
      efficacy of APCs for healing and regeneration of hard and soft tissues in
      patients undergoing regenerative surgical procedures for the treatment of
      intrabony defects, having a follow-up of at least 9 months. Included studies
      underwent risk of bias assessment and data extraction. The main variables
      evaluated for efficacy were: pocket depth (PD), clinical attachment level (CAL),
      radiographic bone filling, and postoperative pain. The effect of APCs adjunct was
      evaluated for the following procedures: open flap debridement (OFD) alone, OFD
      plus grafting of the defect with autogenous bone or bone substitutes, and
      grafting in combination with a covering membrane for guided tissue regeneration
      (GTR). Platelet-rich fibrin (PRF) has a significant additive effect when used
      along with OFD. Platelet-rich plasma (PRP) has a significant additive effect when
      used along with bone grafts. Conversely, PRP was found to be ineffective when
      used in combination with GTR procedures. No study evaluated the effect of APCs on
      postoperative pain. Platelet-rich plasma may be used advantageously as an adjunct
      to grafting materials, but not in combination with GTR, for treatment of
      intrabony defects. Moreover, PRF can be effective as a sole regenerative
      material, in combination with OFD. There is still a lack of evidence regarding
      the effect of PRF in combination with grafting materials and GTR, the effect of
      other types of APCs such as plasma rich in growth factors, and the effect of APCs
      on postoperative pain. 

PMID- 25048154
TI  - Preparation of core-shell nanofibers with selectively localized CNTs from Shish
      Kebab-like hierarchical composite micelles.
AB  - A novel and facile bottom-up strategy for preparing core-shell nanofibers with
      selectively localized carbon nanotubes is developed using hierarchical composite
      micelles of crystalline-coil copolymer and carbon nanotubes as the building
      blocks. An amphiphilic di-block copolymer of poly (p-dioxanone) (PPDO) and PEG
      (polyethylene glycol) functionalized with pyrene moieties at the chain ends of
      PPDO blocks (Py-PPDO-b-PEG) is designed for constructing composite micelles with
      multiwalled carbon nanotubes (MWCNTs). The self-assembly of Py-PPDO-b-PEG and
      MWCNTs is co-induced by the crystallization of PPDO blocks and the pi-pi stacking
      interactions between pyrene moieties and MWCNTs, resulting in composite micelles
      with "shish kebab"-like nanostructure. A mixture of composite micelles and
      polyvinyl alcohol (PVA) water solution is then used as the spinning solution for
      preparing electrospun nanofibers. The morphologies of the nanofibers with
      different composition are investigated by SEM and TEM. The results suggest that
      the MWCNTs selectively localized in the core of the nanofibers of MWCNTs/Py-PPDO
      b-PEG/PVA. The alignment and interfusion of composite micelles during the
      formation of nanofibers may confine the carbon nanotubes in the hydrophobic core
      region. In contrast, the copolymer without pyrene moieties cannot form composite
      micelles, thus these nanofibers show selective localization of MWCNTs in the PVA
      shell region. 

PMID- 25048155
TI  - Lack of diversity in cancer drug clinical trials may exacerbate racial
      disparities in mortality rates.

PMID- 25048156
TI  - Abnormal anti-quenching and controllable multi-transitions of Bi3+ luminescence
      by temperature in a yellow-emitting LuVO4 :Bi3+ phosphor for UV-converted white
      LEDs.
AB  - Phosphors with an efficient yellow-emitting color play a crucial role in phosphor
      converted white LEDs (pc-WLEDs), but popular yellow phosphors such as YAG:Ce or
      Eu(2+) -doped (oxy)nitrides cannot smoothly meet this seemingly simple
      requirement due to their strong absorptions in the visible range. Herein, we
      report a novel yellow-emitting LuVO(4) :Bi(3+) phosphor that can solve this
      shortcoming. The emission from LuVO(4) :Bi(3+) shows a peak at 576 nm with a
      quantum efficiency (QE) of up to 68 %, good resistance to thermal quenching (T(50
      %) =573 K), and no severe thermal degradation after heating-cooling cycles upon
      UV excitation. The yellow emission, as verified by X-ray photoelectron spectra
      (XPS), originates from the ((3)P(0),(3)P(1))->(1) S0 transitions of Bi(3+).
      Increasing the temperature from 10 to 300 K produces a temperature-dependent
      energy-transfer process between VO(4)(3-) groups and Bi(3+), and further heating
      of the samples to 573 K intensifies the emission. However, it subsequently
      weakens, accompanied by blueshifts of the emission peaks. This abnormal anti
      thermal quenching can be ascribed to temperature-dependent energy transfer from
      VO(4)(3-) groups to Bi(3+), a population redistribution between the excited
      states of (3)P(0) and (3)P(1) upon thermal stimulation, and discharge of
      electrons trapped in defects with a trap depth of 359 K. Device fabrication with
      the as-prepared phosphor LuVO(4) :Bi(3+) has proved that it can act as a good
      yellow phosphor for pc-WLEDs.

PMID- 25048157
TI  - Role of neurologists and diagnostic tests on the management of distal symmetric
      polyneuropathy.
AB  - IMPORTANCE: Distal symmetric polyneuropathy (DSP) is a prevalent condition that
      results in high costs from diagnostic testing. However, the role of neurologists
      and diagnostic tests in patient care is unknown. OBJECTIVE: To determine how
      often neurologists and diagnostic tests influence the diagnosis and management of
      DSP in a community setting. DESIGN, SETTING, AND PARTICIPANTS: In this
      retrospective cohort study, we used a validated case-capture method
      (International Classification of Diseases, Ninth Revision screening technique
      with subsequent medical record abstraction) to identify all patients with a new
      DSP diagnosis treated by community neurologists in Nueces County, Texas, who met
      the Toronto Diabetic Neuropathy Expert Group consensus criteria for probable DSP.
      Using a structured data abstraction process, we recorded diagnostic test results,
      diagnoses rendered (before and after testing), and subsequent management from
      April 1, 2010, through March 31, 2011. MAIN OUTCOMES AND MEASURES: Changes in DSP
      cause and management after diagnostic testing by neurologists. RESULTS: We
      identified 458 patients with DSP followed up for a mean (SD) of 435.3 (44.1)
      days. Neurologists identified a cause of DSP in 291 patients (63.5%) before their
      diagnostic testing. Seventy-one patients (15.5%) had a new DSP cause discovered
      after testing by neurologists. The most common new diagnoses were prediabetes (28
      [6.1%]), vitamin B12 deficiency (20 [4.4%]), diabetes mellitus (8 [1.7%]), and
      thyroid disease (8 [1.7%]). Management changes were common (289 [63.1%]) and
      usually related to neuropathic pain management (224 [48.9%]). A potential disease
      modifying management change was made in 113 patients (24.7%), with the most
      common changes being diabetes management in 45 (9.8%), treatment with vitamins in
      39 (8.5%), diet and exercise in 33 (7.2%), and adjustment of thyroid medications
      in 10 (2.2%). Electrodiagnostic testing and magnetic resonance imaging of the
      neuroaxis rarely led to management changes. CONCLUSIONS AND RELEVANCE:
      Neurologists diagnosed the cause of DSP in nearly two-thirds of patients before
      their diagnostic testing. Inexpensive blood tests for diabetes, thyroid
      dysfunction, and vitamin B12 deficiency allowed neurologists to identify a new
      cause of DSP in 71 patients (15.5%). In contrast, expensive electrodiagnostic
      tests and magnetic resonance imaging rarely changed patient care.

PMID- 25048158
TI  - Analysis of the biosynthesis of antibacterial cyclic dipeptides in Nocardiopsis
      alba.
AB  - Nocardiopsis alba is frequently isolated from environment and has recently been
      suggested as a casual symbiotic actinobacterium of diverse invertebrates. Using
      activity-guided fractionation, we purified two antibacterial cyclic dipeptides,
      cyclo(DeltaPhe-DeltaLeu) (albonoursin) and cyclo(DeltamTyr-DeltaLeu), from a
      culture of Nocardiopsis alba ATCC BAA-2165. Analysis of N. alba genome revealed
      genetic information similar to albonoursin biosynthetic gene cluster, albABC. An
      albABC gene deletion mutant of N. alba was generated. Liquid chromatography-mass
      spectrometry analysis showed that the mutant could not produce the cyclic
      dipeptides. Cyclic dipeptide production in the mutant was restored by genetic
      complementation with the albABC cloned in a native plasmid of Nocardiopsis. beta
      Glucuronidase reporter assays with a second mutant construct, in which albABC
      promoter is transcriptionally fused to the reporting gene gusA, indicated that
      albABC gene expression was subject to osmoregulation. The system presented will
      be used to study the metabolic and genetic control of cyclic dipeptide
      biosynthesis in Nocardiopsis. 

PMID- 25048159
TI  - The role of stress in colicin regulation.
AB  - Bacteriocins produced by Enterobacteriaceae are high molecular weight toxic
      proteins that kill target cells through a variety of mechanisms, including pore
      formation and nucleic acid degradation. What is remarkable about these toxins is
      that their expression results in death to the producing cells and therefore
      bacteriocin induction have to be tightly regulated, often confined to times of
      stress. Information on the regulation of bacteriocins produced by enteric
      bacteria is sketchy as their expression has only been elucidated in a handful of
      bacteria. Here, we review the known regulatory mechanisms of enteric bacteriocins
      and explore the expression of 12 of them in response to various triggers: DNA
      damaging agents, stringent response, catabolite repression, oxidative stress,
      growth phase, osmolarity, cold shock, nutrient deprivation, anaerobiosis and pH
      stress. Our results indicate that the expression of bacteriocins is mostly
      confined to mutagenic triggers, while all other triggers tested are limited
      inducers. 

PMID- 25048161
TI  - A mix-and-read fluorescence strategy for the switch-on probing of kinase activity
      based on an aptameric-peptide/graphene-oxide platform.
AB  - Protein kinase plays a vital role in regulating signal-transduction pathways and
      its simple and quick detection is highly desirable because traditional kinase
      assays typically rely on a time-consuming kinase-phosphorylation process (ca. 1
      h). Herein, we report a new and rapid fluorescence-based sensing platform for
      probing the activity of protein kinase that is based on the super-quenching
      capacity of graphene oxide (GO) nanosheets and specific recognition of the
      aptameric peptide (FITC-IP20). On the GO/peptide platform, the fluorescence
      quenching of FITC-IP20 that is adsorbed onto GO can be restored by selective
      binding of active protein kinase to the aptameric peptide, thereby resulting in
      the fast switch-on detection of kinase activity (ca. 15 min). The feasibility of
      this method has been demonstrated by the sensitive measurement of the activity of
      cAMP-dependent protein kinase (PKA), with a detection limit of 0.053 mU MUL(-1).
      This assay technique was also successfully applied to the detection of kinase
      activation in cell lysate.

PMID- 25048160
TI  - Cortical pyroglutamate amyloid-beta levels and cognitive decline in Alzheimer's
      disease.
AB  - Posterior cingulate cortex (PCC) accumulates amyloid-beta (Abeta) early in
      Alzheimer's disease (AD). The relative concentrations of full-length Abeta and
      truncated, pyroglutamate-modified Abeta (NpE3) forms, and their correlations to
      cognitive dysfunction in AD, are unknown. We quantified AbetaNpE3-42, AbetaNpE3
      40, Abeta1-42, and Abeta1-40 concentrations in soluble (nonfibrillar) and
      insoluble (fibrillar) pools in PCC from subjects with an antemortem clinical
      diagnosis of no cognitive impairment, mild cognitive impairment, or mild-moderate
      AD. In clinical AD, increased PCC concentrations of Abeta were observed for all
      Abeta forms in the insoluble pool but only for Abeta1-42 in the soluble pool.
      Lower Mini-Mental State Exam and episodic memory scores correlated most strongly
      with higher concentrations of soluble and insoluble Abeta1-42. Greater
      neuropathology severity by Consortium to Establish a Registry for Alzheimer's
      Disease and National Institute on Aging-Reagan pathologic criteria was associated
      with higher concentrations of all measured Abeta forms, except soluble AbetaNpE3
      40. Low concentrations of soluble pyroglutamate Abeta across clinical groups
      likely reflect its rapid sequestration into plaques, thus, the conversion to
      fibrillar Abeta may be a therapeutic target. 

PMID- 25048162
TI  - Understanding a host-guest model system through 129Xe NMR spectroscopic
      experiments and theoretical studies.
AB  - Gaining an understanding of the nature of host-guest interactions in
      supramolecular complexes involving heavy atoms is a difficult task. Described
      herein is a robust simulation method applied to complexes between xenon and
      members of a cryptophane family. The calculated chemical shift of xenon caged in
      a H2O2 probe, as modeled by quantum chemistry with complementary-orbital,
      topological, and energy-decomposition analyses, is in excellent agreement with
      that observed in hyperpolarized (129)Xe NMR spectra. This approach can be
      extended to other van der Waals complexes involving heavy atoms.

PMID- 25048163
TI  - Influenza immunization in Canada's low-income population.
AB  - BACKGROUND: Immunization offers the best protection from influenza infection.
      Little evidence describes disparities in immunization uptake among low-income
      individuals. Higher rates of chronic disease put this population at increased
      risk of influenza-related complications. This analysis examines if the type of
      main source of household income in low-income groups affects influenza
      immunization uptake. We hypothesized that individuals on social assistance have
      less access to immunization compared to those with employment earnings or
      seniors' benefits. METHODS: Data was obtained from the Canadian Community Health
      Survey annual component 2009-2010. A total of 10,373 low-income respondents
      (<20,000$ Canadian per annum) were included. Logistic regression, stratified
      according to type of provincial publicly funded immunization program, was used to
      examine the association between influenza immunization (in the last 12 months)
      and main source of household income (employment earnings; social assistance as a
      combination of employment insurance or worker's compensation or welfare; or
      seniors' benefits). RESULTS: Overall, 32.5% of respondents reported receiving
      influenza immunization. In multivariable analysis of universal publicly funded
      influenza immunization programs, those reporting social assistance (AOR 1.24, 95%
      CI 1.02-1.51) or seniors' benefits (AOR 1.56, 95% CI 1.23-1.98) were more likely
      to be immunized compared to those reporting employment earnings. Similar results
      were observed for high-risk programs. CONCLUSIONS: Among the low-income sample,
      overall influenza immunization coverage is low. Those receiving social assistance
      or seniors' benefits may have been targeted due to higher rates of chronic
      disease. Programs reaching the workforce may be important to attain broader
      coverage. However, CCHS data was collected during the H1N1 pandemic influenza,
      thus results may not be generalizable to influenza immunization in non-pandemic
      years.

PMID- 25048164
TI  - Infanticide and illegal infant abandonment in Malaysia.
AB  - Infant abandonment and infanticide are poorly understood in Malaysia. The
      information available in the public arena comes predominantly from anecdotal
      sources. The aim of this study was to describe the prevalence and characteristics
      of infanticide and illegal infant abandonment in Malaysia and to estimate annual
      rates for the most recent decade. Summaries of data about infanticide and illegal
      infant abandonment were gathered from police records; the annual number of live
      births was ascertained from the national registry. The estimated inferred
      infanticide rates for Malaysia were compared with the infanticide rates among
      countries of very high, high, medium, and low rankings on the Human Development,
      Gender Inequality, and Gini indices. From 1999 to 2011, 1,069 cases of illegal
      infant abandonment were recorded and 1,147 people were arrested as suspected
      perpetrators. The estimated inferred infanticide rate fluctuated between 4.82 and
      9.11 per 100,000 live births, a moderate rate relative to the infanticide rates
      of other countries. There are substantial missing data, with details undocumented
      for about 78-87% of cases and suspected perpetrators. Of the documented cases, it
      appeared that more boys than girls were victims and that suspected perpetrators
      were predominantly Malays who were women, usually mothers of the victim; the
      possibility of arrest bias must be acknowledged. Economic and social inequality,
      particularly gender inequality, might contribute to the phenomena of infanticide
      and abandonment. Strategies to reduce rates of infanticide and illegal infant
      abandonment in Malaysia will require strengthening of the surveillance system and
      attention to the gender-based inequalities that underpin human development. 

PMID- 25048165
TI  - Harnessing CRISPR-Cas9 immunity for genetic engineering.
AB  - CRISPR-Cas encodes an adaptive immune system that defends prokaryotes against
      infectious viruses and plasmids. Immunity is mediated by Cas nucleases, which use
      small RNA guides (the crRNAs) to specify a cleavage site within the genome of
      invading nucleic acids. In type II CRISPR-Cas systems, the DNA-cleaving activity
      is performed by a single enzyme Cas9 guided by an RNA duplex. Using synthetic
      single RNA guides, Cas9 can be reprogrammed to create specific double-stranded
      DNA breaks in the genomes of a variety of organisms, ranging from human cells to
      bacteria, and thus constitutes a powerful tool for genetic engineering. Here we
      describe recent advancements in our understanding of type II CRISPR-Cas immunity
      and how these studies led to revolutionary genome editing applications. 

PMID- 25048166
TI  - The spore surface of intestinal isolates of Bacillus subtilis.
AB  - Bacillus subtilis has been used for over 50 years as a model organism for
      biochemistry, genetic, molecular biology and cell biology studies. More recently,
      its spore has been proposed as a platform to display heterologous proteins and as
      a vehicle for mucosal vaccination. We characterize here the spore surface of four
      human intestinal strains of B. subtilis, previously identified as able to grow
      anaerobically and form biofilm. These properties, lost in laboratory strains, are
      relevant for the colonization of human mucosal sites and likely to improve the
      efficiency of strains to be used for mucosal delivery. Our characterization is an
      essential preliminary step for the development of these intestinal strains as
      display systems and has indicated that spores of at least one of them are more
      efficient than the laboratory strain for the non-recombinant display of two model
      heterologous proteins. 

PMID- 25048167
TI  - Nab-paclitaxel: a flattering facelift.
AB  - The application of nanotechnology in oncology has increased the efficacy and
      efficiency of some cytotoxic agents. The paradigm in this field is nab
      paclitaxel, a soluble form of paclitaxel that is linked to albumin nanoparticles.
      The development of nanotechnology as a delivery system for paclitaxel has
      provided better pharmacokinetic and pharmacodynamic characteristics, neutralizing
      its hydrophobicity. This procedure significantly improves the treatment of
      metastatic breast cancer compared to conventional paclitaxel-based therapies,
      including other type of cancers such as metastatic pancreatic cancer, stage IIIB
      IV non-small cell lung cancer (NSCLC) and metastatic melanoma. In these last
      cases, significant differences were found in primary end-points for patients
      treated with nab-paclitaxel-based chemotherapy compared to those treated with
      conventional treatments. The application of nanotechnology in cancer treatment
      may also improve the efficacy of other known drugs, as a result of improved
      pharmacokinetic and pharmacodynamic profiles, similarly to paclitaxel. 

PMID- 25048168
TI  - Biosynthesis and characterization of polyhydroxyalkanoates produced by an extreme
      halophilic bacterium, Halomonas nitroreducens, isolated from hypersaline ponds.
AB  - AIMS: Morphological, biochemical and genotypic characterization of a halophilic
      bacterium isolated from hypersaline ponds located at Las Coloradas (Rio Lagartos,
      Yucatan, Mexico). Characterization of polymer produced by this strain was also
      performed. METHODS AND RESULTS: Twenty strains were isolated from water samples
      of salt ponds and selected based on both morphological features and their PHA
      storage capacity, which were determined by SEM and staining methods with Nile red
      and Nile blue, respectively; strains were also analysed by the fluorescence
      imaging technique. Among them, JCCOL25.8 strain showed the highest production of
      PHA's reason why phenotypic and genotypic characterization was performed; this
      strain was identified as Halomonas nitroreducens. Polymer produced by this strain
      was characterized by FTIR, DSC, GPC and EDX spectroscopy. Results indicated that
      the biosynthesized polymer was polyhydroxybutyrate (PHB) which had a melting peak
      at 170 degrees C and a crystallinity percentage of about 36%. CONCLUSIONS: Based
      on phenotypic and genotypic aspects, JCCOL25.8 strain was identified as H.
      nitroreducens and it was capable to accumulate PHB. SIGNIFICANCE AND IMPACT OF
      THE STUDY: To our knowledge, there is only one study published on the
      biosynthesis of PHA's by H. nitroreducens strains, although the characterization
      of the obtained polymer was not reported.

PMID- 25048169
TI  - Non-coding RNA: Zooming in on lncRNA functions.

PMID- 25048171
TI  - Genome-wide determination of poly(A) sites in Medicago truncatula: evolutionary
      conservation of alternative poly(A) site choice.
AB  - BACKGROUND: Alternative polyadenylation (APA) plays an important role in the post
      transcriptional regulation of gene expression. Little is known about how APA
      sites may evolve in homologous genes in different plant species. To this end,
      comparative studies of APA sites in different organisms are needed. In this
      study, a collection of poly(A) sites in Medicago truncatula, a model system for
      legume plants, has been generated and compared with APA sites in Arabidopsis
      thaliana. RESULTS: The poly(A) tags from a deep-sequencing protocol were mapped
      to the annotated M. truncatula genome, and the identified poly(A) sites used to
      update the annotations of 14,203 genes. The results show that 64% of M.
      truncatula genes possess more than one poly(A) site, comparable to the
      percentages reported for Arabidopsis and rice. In addition, the poly(A) signals
      associated with M. truncatula genes were similar to those seen in Arabidopsis and
      other plants. The 3'-UTR lengths are correlated in pairs of orthologous genes
      between M. truncatula and Arabidopsis. Very little conservation of intronic
      poly(A) sites was found between Arabidopsis and M. truncatula, which suggests
      that such sites are likely to be species-specific in plants. In contrast, there
      is a greater conservation of CDS-localized poly(A) sites in these two species. A
      sizeable number of M. truncatula antisense poly(A) sites were found. A high
      percentage of the associated target genes possess Arabidopsis orthologs that are
      also associated with antisense sites. This is suggestive of important roles for
      antisense regulation of these target genes. CONCLUSIONS: Our results reveal some
      distinct patterns of sense and antisense poly(A) sites in Arabidopsis and M.
      truncatula. In so doing, this study lends insight into general evolutionary
      trends of alternative polyadenylation in plants.

PMID- 25048172
TI  - Isomeric routes to Schiff-base single-layered covalent organic frameworks.
AB  - With graphene-like topology and designable functional moieties, single-layered
      covalent organic frameworks (sCOFs) have attracted enormous interest for both
      fundamental research and application prospects. As the growth of sCOFs involves
      the assembly and reaction of precursors in a spatial defined manner, it is of
      great importance to understand the kinetics of sCOFs formation. Although several
      large families of sCOFs and bulk COF materials based on different coupling
      reactions have been reported, the synthesis of isomeric sCOFs by exchanging the
      coupling reaction moieties on precursors has been barely explored. Herein, a
      series of isomeric sCOFs based on Schiff-base reaction is designed to understand
      the effect of monomer structure on the growth kinetics of sCOFs. The distinctly
      different local packing motifs in the mixed assemblies for the two isomeric
      routes closely resemble to those in the assemblies of monomers, which affect the
      structural evolution process for highly ordered imine-linked sCOFs. In addition,
      surface diffusion of monomers and the molecule-substrate interaction, which is
      tunable by reaction temperature, also play an important role in structural
      evolutions. This study highlights the important roles of monomer structure and
      reaction temperature in the design and synthesis of covalent bond connected
      functional nanoporous networks. 

PMID- 25048170
TI  - Epigenetic reprogramming in plant sexual reproduction.
AB  - Epigenetic reprogramming consists of global changes in DNA methylation and
      histone modifications. In mammals, epigenetic reprogramming is primarily
      associated with sexual reproduction and occurs during both gametogenesis and
      early embryonic development. Such reprogramming is crucial not only to maintain
      genomic integrity through silencing transposable elements but also to reset the
      silenced status of imprinted genes. In plants, observations of stable
      transgenerational inheritance of epialleles have argued against reprogramming.
      However, emerging evidence supports that epigenetic reprogramming indeed occurs
      during sexual reproduction in plants and that it has a major role in maintaining
      genome integrity and a potential contribution to epiallelic variation. 

PMID- 25048173
TI  - The rice endophyte Harpophora oryzae genome reveals evolution from a pathogen to
      a mutualistic endophyte.
AB  - The fungus Harpophora oryzae is a close relative of the pathogen Magnaporthe
      oryzae and a beneficial endosymbiont of wild rice. Here, we show that H. oryzae
      evolved from a pathogenic ancestor. The overall genomic structures of H. and M.
      oryzae were found to be similar. However, during interactions with rice, the
      expression of 11.7% of all genes showed opposing trends in the two fungi,
      suggesting differences in gene regulation. Moreover, infection patterns,
      triggering of host defense responses, signal transduction and nutritional
      preferences exhibited remarkable differentiation between the two fungi. In
      addition, the H. oryzae genome was found to contain thousands of loci of
      transposon-like elements, which led to the disruption of 929 genes. Our results
      indicate that the gain or loss of orphan genes, DNA duplications, gene family
      expansions and the frequent translocation of transposon-like elements have been
      important factors in the evolution of this endosymbiont from a pathogenic
      ancestor. 

PMID- 25048175
TI  - Early and late menarche and risk of depressive symptoms in young adulthood.
AB  - We investigated whether girls experiencing early menarche have an increased risk
      of depression during young adulthood. This study used data collected in the
      Growing Up Today Study (N = 9,039), an ongoing prospective cohort of the
      daughters of women enrolled in the Nurses' Health Study II. After excluding girls
      who were postmenarcheal at baseline in 1996, <20 or >=26 years old in 2007, or
      missing data on key covariates, the final sample size was 3,711. Self-reported
      age at menarche was collected annually. Depressive symptomatology was measured in
      2007 using the 10-item Center for Epidemiologic Studies Depression (CES-D-10)
      score. Sixteen percent of girls (N = 596) reported high levels of depressive
      symptoms (CES-D-10 >= 14) in 2007. Neither early nor late menarche was associated
      with high depressive symptoms (for early vs. normative menarche, odds ratio (OR)
      = 1.08, 95 % confidence interval (CI) = 0.85-1.38; for late vs. normative
      menarche, OR = 0.91, 95 % CI = 0.70-1.18) or with differences in continuous CES-D
      10 score in young adulthood. Although previous studies suggest that girls with
      early menarche suffer from an increased risk of adolescent depression, this does
      not appear to persist into young adulthood. 

PMID- 25048177
TI  - Monitoring tool of transcatheter atrial septal defect: transesophageal
      echocardiography or transthoracic echocardiography?

PMID- 25048176
TI  - Identification and validation of quantitative real-time reverse transcription PCR
      reference genes for gene expression analysis in teak (Tectona grandis L.f.).
AB  - BACKGROUND: Teak (Tectona grandis L.f.) is currently the preferred choice of the
      timber trade for fabrication of woody products due to its extraordinary qualities
      and is widely grown around the world. Gene expression studies are essential to
      explore wood formation of vascular plants, and quantitative real-time reverse
      transcription PCR (qRT-PCR) is a sensitive technique employed for quantifying
      gene expression levels. One or more appropriate reference genes are crucial to
      accurately compare mRNA transcripts through different tissues/organs and
      experimental conditions. Despite being the focus of some genetic studies, a lack
      of molecular information has hindered genetic exploration of teak. To date, qRT
      PCR reference genes have not been identified and validated for teak. RESULTS:
      Identification and cloning of nine commonly used qRT-PCR reference genes from
      teak, including ribosomal protein 60s (rp60s), clathrin adaptor complexes medium
      subunit family (Cac), actin (Act), histone 3 (His3), sand family (Sand), beta
      Tubulin (Beta-Tub), ubiquitin (Ubq), elongation factor 1-alpha (Ef-1alpha), and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Expression profiles of these
      genes were evaluated by qRT-PCR in six tissue and organ samples (leaf, flower,
      seedling, root, stem and branch secondary xylem) of teak. Appropriate gene
      cloning and sequencing, primer specificity and amplification efficiency was
      verified for each gene. Their stability as reference genes was validated by
      NormFinder, BestKeeper, geNorm and Delta Ct programs. Results obtained from all
      programs showed that TgUbq and TgEf-1alpha are the most stable genes to use as
      qRT-PCR reference genes and TgAct is the most unstable gene in teak. The relative
      expression of the teak cinnamyl alcohol dehydrogenase (TgCAD) gene in lignified
      tissues at different ages was assessed by qRT-PCR, using TgUbq and TgEf-1alpha as
      internal controls. These analyses exposed a consistent expression pattern with
      both reference genes. CONCLUSION: This study proposes a first broad collection of
      teak tissue and organ mRNA expression data for nine selected candidate qRT-PCR
      reference genes. NormFinder, Bestkeeper, geNorm and Delta Ct analyses suggested
      that TgUbq and TgEf-1alpha have the highest expression stability and provided
      similar results when evaluating TgCAD gene expression, while the commonly used
      Act should be avoided.

PMID- 25048178
TI  - Combination of pulse wave velocity with clinical factors as a promising tool to
      predict major adverse cardiac events after percutaneous coronary intervention.
AB  - BACKGROUND: The relationship between aortic stiffness and coronary artery disease
      has been proven. Logistic Clinical SYNTAX score (LogCSS), which combined the
      anatomical evaluation of coronary artery disease and three clinical factors (age,
      left ventricular ejection fraction, and creatinine clearance), showed improved
      predictive value for cardiovascular events in patients after percutaneous
      coronary intervention (PCI). The combination of pulse wave velocity (PWV) and
      clinical factors may show equivalent predictive value. METHODS: Three hundred and
      seventy-six patients who were diagnosed with non-ST-segment elevation coronary
      syndrome (ACS) and showed at least one >=50% angiographic stenosis in a major
      coronary artery were enrolled. The Clinical PWV score was calculated by assigning
      points to different levels of age, creatinine clearance, left ventricular
      ejection fraction, and carotid-femoral PWV (cfPWV). The points for cfPWV were
      determined based on the cutoff values of quintiles (model 1) or the relationship
      between cfPWV and SYNTAX scores (model 2). The predictive values of LogCSS and
      Clinical PWV score for 3-year major adverse cardiac events (MACE), which were
      defined as all-cause death, nonfatal myocardial infarction, and nonfatal target
      vessel revascularization, were analyzed in 298 patients undergoing PCI. RESULTS:
      The Clinical PWV score based on model 2 demonstrated a similar predictive ability
      for 3-year MACE compared with LogCSS (AUC 0.72 vs. 0.75; p=0.11). The AUC of
      LogCSS was significantly higher than the AUC of Clinical PWV score based on model
      1 (AUC=0.70, p=0.03). Compared with cfPWV in isolation (AUC=0.61), Clinical PWV
      score from model 2 showed significantly better predictive power (p=0.03).
      CONCLUSION: Combination of PWV with age, creatinine clearance, and left
      ventricular ejection fraction appears to be a promising tool to predict MACE
      after PCI in patients with ACS.

PMID- 25048179
TI  - Hyperthermia inhibited the migration of tongue squamous cell carcinoma through
      TWIST2.
AB  - BACKGROUND: Hyperthermia has been shown promising in the treatment of head and
      neck squamous cell carcinoma (HNSCC); however, the mechanism underlying
      hyperthermia reducing tumor metastasis is poorly elucidated. TWIST2, an important
      transcription factor of epithelial-mesenchymal transition (EMT), plays a critical
      role in the tumor progression and metastasis. The role of TWIST2 in tongue
      squamous cell carcinoma (TSCC) and its association with hyperthermia still have
      not been reported. METHOD: The correlations between TWIST2 expression and the
      clinical-pathologic characteristics of 89 patients with TSCC were evaluated by
      immunohistochemical staining. TSCC cell lines transfected with siRNA against
      TWIST2 were heated for 40 min at 42.5 degrees C, and the migration capability of
      cells was examined by migration assay. Xenograft tumors in nude mice were treated
      by hyperthermia, and TWIST2 expression was measured. RESULTS: Our data showed
      that TWIST2 expression was associated with the metastasis of human TSCC. In
      Tca8113 and Cal-27 cells, TWIST2-siRNA treatment can reduce cell migration
      ability and has no effect on the cell proliferation and apoptosis. Hyperthermia
      can decrease the level of TWIST2 in TSCC and inhibit the migration of cells.
      CONCLUSIONS: This demonstrated that hyperthermia might decrease the migration of
      Tca8113 and Cal-27 cells by reducing TWIST2 expression. Altogether, these
      findings suggest an as yet undescribed link between TWIST2 and hyperthermia in
      TSCC.

PMID- 25048180
TI  - Association between methylation of the glucocorticoid receptor gene, childhood
      maltreatment, and clinical severity in borderline personality disorder.
AB  - The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of
      stress responses. Increased methylation of the promoter region of the
      glucocorticoid receptor gene (NR3C1) has been described both in subjects with
      history of childhood trauma and in patients with Borderline Personality Disorder
      (BPD). However, no data on the possible association between a higher methylation
      of this gene and clinical severity is available. The aim of this study was to
      evaluate the association between NR3C1 methylation status, the history of
      childhood trauma, and current clinical severity in subjects with BPD. A sample of
      281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic
      interviews) was recruited. Clinical variables included previous hospitalizations,
      self-injurious behavior, and self-reported history of childhood trauma. DNA was
      extracted from peripheral blood. The results indicated a significant positive
      correlation between NR3C1 methylation status and childhood maltreatment
      (specifically physical abuse). In addition, a positive correlation between
      methylation status and clinical severity (DIB-R total score and hospitalizations)
      was observed. These findings suggest that NR3C1 methylation in subjects with BPD
      may be associated not only with childhood trauma but also with clinical severity,
      adding new evidence to the involvement of gene-environment interactions in this
      disorder. 

PMID- 25048181
TI  - Endoscopic assessment of reflux esophagitis concurrent with hiatal hernia in male
      Japanese patients with obstructive sleep apnea.
AB  - OBJECTIVE: The pathogenetic relationship underlying the high prevalence of
      gastroesophageal reflux disease (GERD) in patients with obstructive sleep apnea
      (OSA) remains unclear. In addition, GERD has not been adequately assessed by
      endoscopy in patients with OSA. The purpose of this study was to use endoscopy to
      investigate potential interactions among reflux esophagitis, hiatal hernia (HH)
      and OSA. MATERIAL AND METHODS: A total of 243 consecutive male Japanese
      participants who underwent both overnight ambulatory polygraphic monitoring and
      esophagogastroduodenoscopy were retrospectively evaluated in a cross-sectional
      study. The prevalence and severity of HH and reflux esophagitis were assessed
      according to the Los Angeles classification and the Makuuchi classification,
      respectively. Associations among reflux esophagitis, HH and OSA were examined by
      univariate and multivariate analyses. RESULTS: OSA was diagnosed in 98
      individuals (40.3%). Endoscopy-confirmed esophagitis (p = 0.027) and HH (p <
      0.001) were significantly more prevalent among patients with OSA. Multivariate
      regression model analysis adjusted for age, body mass index, visceral obesity
      represented by waist circumference, presence of OSA, concurrence of OSA and HH,
      smoking, and alcohol consumption yielded OSA as the only variable significantly
      associated with HH (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.35
      4.99; p = 0.004), while concurrence of OSA and HH was related to reflux
      esophagitis (OR, 3.59; CI, 1.87-6.92; p < 0.001). CONCLUSIONS: OSA was associated
      with HH and concurrent OSA and HH with reflux esophagitis in male Japanese
      patients with OSA. Our results support the hypothesis that complicating HH may
      link reflux esophagitis to OSA.

PMID- 25048182
TI  - Optical spectroscopy and imaging for early lung cancer detection: a review.
AB  - Over the last 15 years, optical spectroscopy and imaging has been intensively
      studied to improve the detection and localization of early lung cancer.
      Autofluorescence bronchoscopy (AFB) is the most successfully developed technique
      and has significantly improved the detection sensitivity of early lung cancer. In
      this review, the optical principles behind white-light and autofluorescence
      bronchoscopy, as well as the role of AFB in the diagnosis of early lung cancer
      and the overall management of patients with early lung cancer are discussed.
      Other newest development such as Raman spectroscopy and simultaneous imaging and
      spectroscopy measurements are also highlighted. 

PMID- 25048183
TI  - Interstitial photodynamic therapy for prostate cancer: a developing modality.
AB  - Patients with early stage prostate cancer are generally treated with either a
      radical prostatectomy or radiotherapy. While both approaches have good survival
      outcomes, they are associated with significant side effects and non-trivial
      failure rates. Photodynamic therapy has been studied as a possible treatment for
      both recurrent and primary prostate cancer. Interstitial photodynamic therapy
      requires strict dosimetry, mandating an understanding of photosensitizer
      concentration, tissue oxygenation, and light fluence. Preclinical studies have
      investigated the optical characteristics of prostate tissue showing variability
      both prior to and during photodynamic therapy. Canine studies have been
      undertaken demonstrating necrosis of the glandular epithelium to depths ranging
      from 1 to 17mm from a single light source depending on the photosensitizer used.
      Necrosis is typically followed by glandular atrophy with maintenance of the gross
      prostatic architecture. Urinary complications in the canine studies were more
      prominent when transurethral light was used and often occurred in a dose
      dependent fashion. Few clinical trials have been undertaken to date investigating
      photodynamic therapy of the prostate in patients. The limited data that are
      available suggest that photodynamic therapy is tolerable in patients with
      recurrent and primary disease. This review summarizes the preclinical and
      clinical work in photodynamic therapy in the prostate and suggests areas of
      future research which must be addressed before the technique can become a
      practical option for patients. 

PMID- 25048184
TI  - 5-Aminolaevulinic acid compared to polyhematoporphyrin photosensitization for
      photodynamic therapy of malignant bronchial and esophageal stenosis: clinical
      experience.
AB  - BACKGROUND AND OBJECTIVE: Polyhematoporphyrins (PhP) as sensitizers for
      photodynamic therapy (PDT) in malignant bronchial and esophageal stenosis carry
      the risk of prolonged photosensitivity of the skin. New line sensitizers such as
      5-aminolaevulinic acid (ALA) with low rates of skin phototoxicity appear to be
      promising alternatives. The aim of this study was to evaluate the efficacy of ALA
      compared to PhP for PDT regarding phototoxicity of the skin, reduction of tumour
      stenosis and tumour length and Karnofsky performance status. PATIENTS AND
      METHODS: After diagnostic work-up, photosensitization was done in 38 patients
      with ALA (60mg/kg body weight, oral, 6-8h prior to PDT) and in 51 patients with
      PhP (2mg/kg body weight, i.v., 48h before PDT). The light dose was calculated as
      300J/cm fibre tip. Light at 630nm was applied using a pumped dye laser. In both
      groups, additional hyperbaric oxygenation was applied at a level of 2 bar
      absolute pressure. RESULTS: Improvement regarding stenosis diameter, tumour
      length and Karnofsky performance status could be obtained in both treatment arms
      with a significant difference in favour of the PhP-group, P = 0.00073; 0.000014,
      and 0.00015, respectively. No sunburn or other major treatment related
      complications occurred in either treatment arms. CONCLUSION: Photosensitization
      with PhP compared to ALA seems to be more effective in PDT of malignant bronchial
      and esophageal stenosis.

PMID- 25048185
TI  - Photodynamic therapy for pancreatic carcinoma: experimental and clinical studies.
AB  - Pancreatic carcinoma is the sixth leading cause of cancer-related mortality in
      the United Kingdom, with an overall 5-year survival of less than 5%. Attempted
      curative surgery is possible in less than 20% of cases and is associated with a 5
      year survival of just 10-20%. Palliative radio-chemotherapy improves symptoms of
      pancreatic cancer but rarely extends median survival beyond 12 months. There is a
      need to develop novel therapies that improve outcome. Photodynamic therapy, which
      is a way of producing localised non-thermal tissue necrosis with light, is
      currently under evaluation as a treatment for pancreatic cancer. This review will
      examine some of the mechanisms underlying photodynamic therapy, and the
      preclinical work, which has led to this treatment being piloted in human studies.

PMID- 25048186
TI  - Photodynamic therapy for chest wall recurrence from breast cancer.
AB  - Breast cancer is common with over 230,000 new cases diagnosed each year in North
      America alone. While great strides have been made to achieve excellent cancer
      control and survival, a significant minority of patients fail locally. While
      initial salvage to regain disease control is of the utmost importance, it is not
      universally successful. This leads to a therapeutic quagmire. Additional surgery,
      radiation and chemo-hormonal therapy are possible, but they are usually highly
      morbid with low success rates. Photodynamic therapy appears to be an
      underutilized salvage modality for this unfortunate patient population. This
      report analyzes and reviews the role of photodynamic therapy for patients with
      chest wall re-recurrence from breast cancer. 

PMID- 25048187
TI  - Fluence-rate effects upon m-THPC photobleaching in a formalin-fixed cell system.
AB  - We have applied a micro-spectroscopic technique in order to record the laser
      induced fluorescence emission of the PDT photosensitiser m-THPC (Foscan) from
      micron-scale locations within individual formalin-fixed keratinocytes. We
      demonstrate that m-THPC is highly photolabile in this cellular environment, and
      that the process of photobleaching can be monitored via the depletion in
      fluorescence emission during continuous irradiation with 410nm laser light. The
      progressive reduction of the characteristic 652nm m-THPC fluorescence peak can be
      described with bi-exponential decay kinetics, consistent with a singlet oxygen
      mediated process. The rate of photobleaching, when plotted as a function of light
      dose, shows inverse fluence-rate dependence. Specifically, the rate of
      photobleaching induced by the higher laser powers appears to be limited by oxygen
      availability, as demonstrated by an increase in the (1/e) bleaching dose.
      Fractionated irradiation provides evidence of intracellular re-oxygenation. These
      results are in qualitative agreement with previous in vitro and in vivo studies,
      which indicate that the photodynamic dose delivered during light irradiation is
      critically dependent upon local fluence rate and oxygen partial pressure. 

PMID- 25048188
TI  - Tissue detection of diphenylchlorin sensitizer (SIM01) by fluorescence and high
      performance liquid chromatography.
AB  - Cancer is today a major problem of public health. Unfortunately, the current
      treatments remain still too often impotent or too heavy compared to the gross
      national product of many countries. The use of PDT in the treatment of the
      malignant tumours currently raises great hopes. This physicochemical method is
      based on the combined action of a nontoxic drug given systematically to the
      patient and of the visible light delivered locally to the tumour using optical
      fibres. The radiation will activate the significant substance preferentially
      fixed on cancerous cells and will cause the death of the tumoral cells while
      releasing from the toxic ridicalizing species which then will deteriorate vital
      cellular targets. Tissue distribution and elimination kinetics of the SIM01 were
      analysed in biological samples from mice tissues by spectrofluorometry and HPLC.
      Measurements were performed 4, 6, 12, 24 and 48h after an intraperitoneal
      injection for SIM01 doses of 2, 5 and 15mgkg(-1). Elimination seemed to concern
      essentially gallbladder, liver and stools, where maximum fluorescence reached,
      respectively, 20,000, 2800 and 15,000cps for 5mgkg(-1), 6h after injection. Among
      the tissues examined with HPLC, the highest SIM01 levels were found in stools,
      urine, liver, gallbladder and spleen. Liver, gallbladder, and stool homogenates
      from drug-treated animals contained an additional peak (16, 7min) detectable only
      after injection of at least 15mgkg(-1). Our HPLC determinations and in vivo
      fluorescence detection of SIM01 gave comparable kinetic profiles. These
      techniques should be considered as complementary rather than exclusive for
      kinetic profiles determination. 

PMID- 25048189
TI  - Pancreatic neuroendocrine tumours: correlation between MSCT features and
      pathological classification.
AB  - OBJECTIVES: We aimed to evaluate the multi-slice computed tomography (MSCT)
      features of pancreatic neuroendocrine neoplasms (P-NENs) and analyse the
      correlation between the MSCT features and pathological classification of P-NENs.
      METHODS: Forty-one patients, preoperatively investigated by MSCT and subsequently
      operated on with a histological diagnosis of P-NENs, were included. Various MSCT
      features of the primary tumour, lymph node, and distant metastasis were analysed.
      The relationship between MSCT features and pathologic classification of P-NENs
      was analysed with univariate and multivariate models. RESULTS: Contrast-enhanced
      images showed significant differences among the three grades of tumours in the
      absolute enhancement (P = 0.013) and relative enhancement (P = 0.025) at the
      arterial phase. Univariate analysis revealed statistically significant
      differences among the tumours of different grades (based on World Health
      Organization [WHO] 2010 classification) in tumour size (P = 0.001), tumour
      contour (P < 0.001), cystic necrosis (P = 0.001), tumour boundary (P = 0.003),
      dilatation of the main pancreatic duct (P = 0.001), peripancreatic tissue or
      vascular invasion (P < 0.001), lymphadenopathy (P = 0.011), and distant
      metastasis (P = 0.012). Multivariate analysis suggested that only peripancreatic
      tissue or vascular invasion (HR 3.934, 95 % CI, 0.426-7.442, P = 0.028) was
      significantly associated with WHO 2010 pathological classification. CONCLUSIONS:
      MSCT is helpful in evaluating the pathological classification of P-NENs. KEY
      POINTS: * P-NENs are potentially malignant, and classification of P-NENs carries
      important prognostic value. * MSCT plays an important role in the diagnosis and
      staging of P-NENs. * Correlations between classification of P-NENs and imaging
      findings have not been systematically evaluated. * MSCT could predict P-NENs
      classification and may be a useful prognostication tool.

PMID- 25048190
TI  - Comparison of high-resolution computed tomography findings between Pseudomonas
      aeruginosa pneumonia and Cytomegalovirus pneumonia.
AB  - OBJECTIVE: To compare pulmonary high-resolution CT (HRCT) findings in patients
      with Pseudomonas aeruginosa pneumonia to HRCT findings in patients with
      Cytomegalovirus (CMV) pneumonia. METHODS: We studied 124 patients (77 men, 47
      women; age range, 20-89 years; mean age, 65.4 years) with P. aeruginosa pneumonia
      and 44 patients (22 men, 22 women; age range, 36-86 years; mean age, 63.2 years)
      with CMV pneumonia. RESULTS: CT findings of consolidation (p < 0.005), bronchial
      wall thickening (p < 0.001), cavity (p < 0.05), and pleural effusion (p < 0.001)
      were significantly more frequent in patients with P. aeruginosa pneumonia than in
      those with CMV pneumonia. Centrilobular nodules, a crazy-paving appearance, and
      nodules were significantly more frequent in patients with CMV pneumonia than in
      those with P. aeruginosa pneumonia (all p < 0.001). CONCLUSION: Pulmonary HRCT
      findings, such as bronchial wall thickening, crazy-paving appearance, and nodules
      may be useful in distinguishing between P. aeruginosa pneumonia and CMV
      pneumonia. KEY POINTS: Distinguishing Pseudomonas aeruginosa pneumonia from
      Cytomegalovirus pneumonia is important. Characteristic features of underlying
      conditions are present in each pneumonia species. Bronchial wall thickening and
      cavities are more frequent in Pseudomonas aeruginosa pneumonia. Nodules and a
      crazy-paving appearance are more frequent in Cytomegalovirus pneumonia.

PMID- 25048191
TI  - Comparing five different iterative reconstruction algorithms for computed
      tomography in an ROC study.
AB  - OBJECTIVES: The purpose of this study was to evaluate lesion conspicuity achieved
      with five different iterative reconstruction techniques from four CT vendors at
      three different dose levels. Comparisons were made of iterative algorithm and
      filtered back projection (FBP) among and within systems. METHODS: An
      anthropomorphic liver phantom was examined with four CT systems, each from a
      different vendor. CTDIvol levels of 5 mGy, 10 mGy and 15 mGy were chosen. Images
      were reconstructed with FBP and the iterative algorithm on the system. Images
      were interpreted independently by four observers, and the areas under the ROC
      curve (AUCs) were calculated. Noise and contrast-to-noise ratios (CNR) were
      measured. RESULTS: One iterative algorithm increased AUC (0.79, 0.95, and 0.97)
      compared to FBP (0.70, 0.86, and 0.93) at all dose levels (p < 0.001 and p =
      0.047). Another algorithm increased AUC from 0.78 with FBP to 0.84 (p = 0.007) at
      5 mGy. Differences at 10 and 15 mGy were not significant (p-values: 0.084-0.883).
      Three algorithms showed no difference in AUC compared to FBP (p-values: 0.008
      1.000). All of the algorithms decreased noise (10-71%) and improved CNR.
      CONCLUSIONS: Only two algorithms improved lesion detection, even though noise
      reduction was shown with all algorithms. KEY POINTS: Iterative reconstruction
      algorithms affected lesion detection differently at different dose levels. One
      iterative algorithm improved lesion detectability compared to filtered back
      projection. Three algorithms did not significantly improve lesion detectability.
      One algorithm improved lesion detectability at the lowest dose level.

PMID- 25048192
TI  - Size-dependent toxicity of silver nanoparticles to bacteria, yeast, algae,
      crustaceans and mammalian cells in vitro.
AB  - The concept of nanotechnologies is based on size-dependent properties of
      particles in the 1-100 nm range. However, the relation between the particle size
      and biological effects is still unclear. The aim of the current paper was to
      generate and analyse a homogenous set of experimental toxicity data on Ag
      nanoparticles (Ag NPs) of similar coating (citrate) but of 5 different primary
      sizes (10, 20, 40, 60 and 80 nm) to different types of organisms/cells commonly
      used in toxicity assays: bacterial, yeast and algal cells, crustaceans and
      mammalian cells in vitro. When possible, the assays were conducted in ultrapure
      water to minimise the effect of medium components on silver speciation. The toxic
      effects of NPs to different organisms varied about two orders of magnitude, being
      the lowest (~0.1 mg Ag/L) for crustaceans and algae and the highest (~26 mg Ag/L)
      for mammalian cells. To quantify the role of Ag ions in the toxicity of Ag NPs,
      we normalized the EC50 values to Ag ions that dissolved from the NPs. The
      analysis showed that the toxicity of 20-80 nm Ag NPs could fully be explained by
      released Ag ions whereas 10 nm Ag NPs proved more toxic than predicted. Using E.
      coli Ag-biosensor, we demonstrated that 10 nm Ag NPs were more bioavailable to E.
      coli than silver salt (AgNO3). Thus, one may infer that 10 nm Ag NPs had more
      efficient cell-particle contact resulting in higher intracellular bioavailability
      of silver than in case of bigger NPs. Although the latter conclusion is initially
      based on one test organism, it may lead to an explanation for "size-dependent"
      biological effects of silver NPs. This study, for the first time, investigated
      the size-dependent toxic effects of a well-characterized library of Ag NPs to
      several microbial species, protozoans, algae, crustaceans and mammalian cells in
      vitro. 

PMID- 25048193
TI  - The sterol-based transcriptional control of human 7-dehydrocholesterol reductase
      (DHCR7): Evidence of a cooperative regulatory program in cholesterol synthesis.
AB  - The enzyme 7-dehydrocholesterol reductase (DHCR7) catalyzes the final step of
      cholesterol synthesis via the Kandutsch-Russell pathway, and is crucial in
      maintaining cellular cholesterol levels. Its absence leads to the devastating
      fetal developmental disorder Smith-Lemli-Opitz Syndrome (SLOS). How this enzyme
      is regulated has implications in controlling not only cholesterol synthesis, but
      also the synthesis of Vitamin D - another product of 7-dehydrocholesterol. In
      this study, we look specifically at how DHCR7 is regulated by the sterol
      regulatory element-binding protein-2 (SREBP-2) transcription factor. Sterol
      regulation has previously been studied in the rat DHCR7 promoter, but we have
      found that its regulatory elements are not all conserved in humans. Rather, the
      human promoter contains two binding sites for SREBP-2 (at -155 and -55) and a
      binding site for the nuclear factor-Y (NF-Y) cofactor (at -136). The -155 site is
      a particularly responsive sterol regulatory element (SRE) which is well conserved
      in mammals, and was possibly overlooked in the rat promoter study. The exact
      location of the weaker -55 site (close to the known rat SRE) may have shifted
      during evolution. Furthermore, we established that the two SREs that bind SREBP-2
      work in cooperation to synergistically activate DHCR7. We have previously
      characterized the SREs in DHCR24, the final enzyme in the alternate Bloch pathway
      of cholesterol synthesis. Here, comparison of the sterol regulation of these
      terminal enzymes demonstrates the unique cooperative system that helps to control
      cholesterol synthesis. 

PMID- 25048194
TI  - Role of the N-terminal hydrophobic residues of DGKepsilon in targeting the
      endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER), comprised of an interconnected membrane network,
      is a site of phospholipid and protein synthesis. The diacylglycerol kinase (DGK)
      enzyme family catalyzes phosphorylation of diacylglycerol to phosphatidic acid.
      Both of these lipids are known not only to serve as second messengers but also to
      represent intermediate precursors of lipids of various kinds. The DGK family is
      targeted to distinct subcellular sites in cDNA-transfected and native cells. Of
      DGKs, DGKepsilon localizes primarily to the ER, suggesting that this isozyme
      plays a role in this organelle. Using experiments with various deletion and
      substitution mutants, this study examined the molecular mechanism of how
      DGKepsilon is targeted to the ER. Results demonstrate that the N-terminal
      hydrophobic sequence 20-40 plays a necessary role in targeting of DGKepsilon to
      the ER. This hydrophobic amino acid segment is predicted to adopt an alpha-helix
      structure, in which Leu22, L25, and L29 are present in mutual proximity, forming
      a hydrophobic patch. When these hydrophobic Leu residues were replaced with
      hydrophilic amino acid Gln, the mutant fragment designated DGKepsilon (20
      40/L22Q,L25Q,L29Q) exhibits diffuse distribution in the cytoplasm. Moreover, full
      length DGKepsilon containing these substitutions, DGKepsilon (L22Q,L25Q,L29Q), is
      shown to distribute diffusely in the cytoplasm. These results indicate that the N
      terminal hydrophobic residues play a key role in DGKepsilon targeting to the ER
      membrane. Functionally, knockdown or deletion of DGKepsilon affects the unfolding
      protein response pathways, thereby rendering the cells susceptible to apoptosis,
      to some degree, under ER stress conditions. 

PMID- 25048195
TI  - Genetic evidence for a normal-weight "metabolically obese" phenotype linking
      insulin resistance, hypertension, coronary artery disease, and type 2 diabetes.
AB  - The mechanisms that predispose to hypertension, coronary artery disease (CAD),
      and type 2 diabetes (T2D) in individuals of normal weight are poorly understood.
      In contrast, in monogenic primary lipodystrophy-a reduction in subcutaneous
      adipose tissue-it is clear that it is adipose dysfunction that causes severe
      insulin resistance (IR), hypertension, CAD, and T2D. We aimed to test the
      hypothesis that common alleles associated with IR also influence the wider
      clinical and biochemical profile of monogenic IR. We selected 19 common genetic
      variants associated with fasting insulin-based measures of IR. We used
      hierarchical clustering and results from genome-wide association studies of eight
      nondisease outcomes of monogenic IR to group these variants. We analyzed genetic
      risk scores against disease outcomes, including 12,171 T2D cases, 40,365 CAD
      cases, and 69,828 individuals with blood pressure measurements. Hierarchical
      clustering identified 11 variants associated with a metabolic profile consistent
      with a common, subtle form of lipodystrophy. A genetic risk score consisting of
      these 11 IR risk alleles was associated with higher triglycerides (beta = 0.018;
      P = 4 * 10(-29)), lower HDL cholesterol (beta = -0.020; P = 7 * 10(-37)), greater
      hepatic steatosis (beta = 0.021; P = 3 * 10(-4)), higher alanine transaminase
      (beta = 0.002; P = 3 * 10(-5)), lower sex-hormone-binding globulin (beta = 
      0.010; P = 9 * 10(-13)), and lower adiponectin (beta = -0.015; P = 2 * 10(-26)).
      The same risk alleles were associated with lower BMI (per-allele beta = -0.008; P
      = 7 * 10(-8)) and increased visceral-to-subcutaneous adipose tissue ratio (beta =
      -0.015; P = 6 * 10(-7)). Individuals carrying >=17 fasting insulin-raising
      alleles (5.5% population) were slimmer (0.30 kg/m(2)) but at increased risk of
      T2D (odds ratio [OR] 1.46; per-allele P = 5 * 10(-13)), CAD (OR 1.12; per-allele
      P = 1 * 10(-5)), and increased blood pressure (systolic and diastolic blood
      pressure of 1.21 mmHg [per-allele P = 2 * 10(-5)] and 0.67 mmHg [per-allele P = 2
      * 10(-4)], respectively) compared with individuals carrying <=9 risk alleles
      (5.5% population). Our results provide genetic evidence for a link between the
      three diseases of the "metabolic syndrome" and point to reduced subcutaneous
      adiposity as a central mechanism.

PMID- 25048196
TI  - Perforin is a novel immune regulator of obesity-related insulin resistance.
AB  - Obesity-related insulin resistance is associated with an influx of pathogenic T
      cells into visceral adipose tissue (VAT), but the mechanisms regulating
      lymphocyte balance in such tissues are unknown. Here we describe an important
      role for the immune cytotoxic effector molecule perforin in regulating this
      process. Perforin-deficient mice (Prf1(null)) show early increased body weight
      and adiposity, glucose intolerance, and insulin resistance when placed on high
      fat diet (HFD). Regulatory effects of perforin on glucose tolerance are
      mechanistically linked to the control of T-cell proliferation and cytokine
      production in inflamed VAT. HFD-fed Prf1(null) mice have increased accumulation
      of proinflammatory IFN-gamma-producing CD4(+) and CD8(+) T cells and M1-polarized
      macrophages in VAT. CD8(+) T cells from the VAT of Prf1(null) mice have increased
      proliferation and impaired early apoptosis, suggesting a role for perforin in the
      regulation of T-cell turnover during HFD feeding. Transfer of CD8(+) T cells from
      Prf1(null) mice into CD8-deficient mice (CD8(null)) resulted in worsening of
      metabolic parameters compared with wild-type donors. Improved metabolic
      parameters in HFD natural killer (NK) cell-deficient mice (NK(null)) ruled out a
      role for NK cells as a single source of perforin in regulating glucose
      homeostasis. The findings support the importance of T-cell function in insulin
      resistance and suggest that modulation of lymphocyte homeostasis in inflamed VAT
      is one possible avenue for therapeutic intervention.

PMID- 25048197
TI  - Pancreastatin-dependent inflammatory signaling mediates obesity-induced insulin
      resistance.
AB  - Chromogranin A knockout (Chga-KO) mice exhibit enhanced insulin sensitivity
      despite obesity. Here, we probed the role of the chromogranin A-derived peptide
      pancreastatin (PST: CHGA(273-301)) by investigating the effect of diet-induced
      obesity (DIO) on insulin sensitivity of these mice. We found that on a high-fat
      diet (HFD), Chga-KO mice (KO-DIO) remain more insulin sensitive than wild-type
      DIO (WT-DIO) mice. Concomitant with this phenotype is enhanced Akt and AMPK
      signaling in muscle and white adipose tissue (WAT) as well as increased FoxO1
      phosphorylation and expression of mature Srebp-1c in liver and downregulation of
      the hepatic gluconeogenic genes, Pepck and G6pase. KO-DIO mice also exhibited
      downregulation of cytokines and proinflammatory genes and upregulation of anti
      inflammatory genes in WAT, and peritoneal macrophages from KO mice displayed
      similarly reduced proinflammatory gene expression. The insulin-sensitive, anti
      inflammatory phenotype of KO-DIO mice is masked by supplementing PST. Conversely,
      a PST variant peptide PSTv1 (PST-NDelta3: CHGA(276-301)), lacking PST activity,
      simulated the KO phenotype by sensitizing WT-DIO mice to insulin. In summary, the
      reduced inflammation due to PST deficiency prevented the development of insulin
      resistance in KO-DIO mice. Thus, obesity manifests insulin resistance only in the
      presence of PST, and in its absence obesity is dissociated from insulin
      resistance.

PMID- 25048198
TI  - Hypospadias and increased risk for neurodevelopmental disorders.
AB  - BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the
      penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether
      this common malformation is associated with increased psychiatric morbidity later
      in life. Studies of individuals with hypospadias also provide an opportunity to
      examine whether difference in androgen signaling is related to neurodevelopmental
      disorders. To elucidate the mechanisms behind a possible association, we also
      studied psychiatric outcomes among brothers of the hypospadias patients. METHODS:
      Registry study within a national cohort of all 9,262 males with hypospadias and
      their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with
      hypospadias and their brothers were matched with controls by year of birth and
      county. The following outcomes were evaluated (1) any psychiatric (2) psychotic,
      (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance
      misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum
      disorders (ASD), (10) intellectual disability, and (11) other
      behavioral/emotional disorders with onset in childhood. RESULTS: Patients with
      hypospadias were more likely to be diagnosed with intellectual disability (OR
      3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and
      behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls.
      Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1)
      and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5)
      in comparison to siblings of healthy individuals. A slightly higher, although not
      statistically significant, risk was found for intellectual disability (1.3; 1.0
      1.9). No relation between other psychiatric diagnosis and hypospadias was found.
      CONCLUSIONS: This is the first study to identify an increased risk for
      neurodevelopmental disorders in patients with hypospadias, as well as an
      increased risk for ASD in their brothers, suggesting a common familial (genetic
      and/or environmental) liability.

PMID- 25048199
TI  - A new method to explore the spectral impact of the piriform fossae on the singing
      voice: benchmarking using MRI-based 3D-printed vocal tracts.
AB  - The piriform fossae are the 2 pear-shaped cavities lateral to the laryngeal
      vestibule at the lower end of the vocal tract. They act acoustically as side
      branches to the main tract, resulting in a spectral zero in the output of the
      human voice. This study investigates their spectral role by comparing numerical
      and experimental results of MRI-based 3D printed Vocal Tracts, for which a new
      experimental method (based on room acoustics) is introduced. The findings support
      results in the literature: the piriform fossae create a spectral trough in the
      region 4-5 kHz and act as formants repellents. Moreover, this study extends those
      results by demonstrating numerically and perceptually the impact of having large
      piriform fossae on the sung output. 

PMID- 25048200
TI  - Preterm subtypes by immigrants' length of residence in Norway: a population-based
      study.
AB  - BACKGROUND: The reduction of the preterm delivery (PTD) rate is a maternal and
      child health target. Elevated rates have been found among several immigrant
      groups, but few studies have distinguished between PTD according to the mode of
      birth start. In addition, migrants' birth outcomes have further been shown to be
      affected by the time in residence; however, the association to PTD subtypes has
      not previously been assessed. In this study we examined if the risk of
      spontaneous and non-spontaneous, or iatrogenic, PTD among immigrants in Norway
      varied according to the length of residence and the country of birth, and
      compared with the risks among the majority population. METHODS: We linked
      population-based birth and immigration data for 40 709 singletons born to
      immigrant women from Iraq, Pakistan, the Philippines, Somalia, Sri Lanka and
      Vietnam and 868 832 singletons born to non-immigrant women from 1990-2009.
      Associations between the length of residence and subtypes of PTD were estimated
      as relative risks (RRs) with 95% confidence intervals (CIs) from multivariable
      models. RESULTS: In total, 48 191 preterm births occurred. Both spontaneous and
      non-spontaneous PTD rates were higher among immigrants (4.8% and 2.0%) than among
      non-immigrants (3.6% and 1.6%). Only non-spontaneous PTD was associated with
      longer lengths of residence (p trend <0.001). Recent immigrants (<5 years of
      residence) and non-immigrants had a similar risk of non-spontaneous PTD, whereas
      immigrants with lengths of residence of 5-9 years, 10-14 years and >= 15 years
      had adjusted RRs of 1.18 [95% CI 1.03,1.35], 1.43 [95% CI 1.20,1.71] and 1.66
      [95% CI 1.41,1.96]. The association was reduced after further adjustments for
      maternal and infant morbidity. Conversely, the risk of spontaneous PTD among
      immigrants was not mitigated by length of residence, but varied with country of
      birth according to the duration of pregnancy in term births. CONCLUSIONS: Non
      spontaneous PTD increased with the length of residence whereas spontaneous PTD
      remained elevated regardless of the length of residence. Policies to improve
      birth outcomes in ethnically mixed populations should address the modifiable
      causes of PTD rather than aiming to reduce absolute PTD rates.

PMID- 25048203
TI  - Bifurcation and oscillation in a time-delay neural mass model.
AB  - The neural mass model developed by Lopes da Silva et al. simulates complex
      dynamics between cortical areas and is able to describe a limit cycle behavior
      for alpha rhythms in electroencephalography (EEG). In this work, we propose a
      modified neural mass model that incorporates a time delay. This time-delay model
      can be used to simulate several different types of EEG activity including alpha
      wave, interictal EEG, and ictal EEG. We present a detailed description of the
      model's behavior with bifurcation diagrams. Through simulation and an analysis of
      the influence of the time delay on the model's oscillatory behavior, we
      demonstrate that a time delay in neuronal signal transmission could cause seizure
      like activity in the brain. Further study of the bifurcations in this new neural
      mass model could provide a theoretical reference for the understanding of the
      neurodynamics in epileptic seizures. 

PMID- 25048202
TI  - Tyrosine phosphatase Shp2 mediates the estrogen biological action in breast
      cancer via interaction with the estrogen extranuclear receptor.
AB  - The extranuclear estrogen receptor pathway opens up novel perspectives in many
      physiological and pathological processes, especially in breast carcinogenesis.
      However, its function and mechanisms are not fully understood. Herein we present
      data identifying Shp2, a SH2-containing tyrosine phosphatase, as a critical
      component of extranuclear ER pathway in breast cancer. The research checked that
      the effect of Shp2 on the tumor formation and growth in animal model and
      investigated the regulation of Shp2 on the bio-effect and signaling transduction
      of estrogen in breast cancer cell lines. The results showed that Shp2 was highly
      expressed in more than 60% of total 151 breast cancer cases. The inhibition of
      Shp2 activity by PHPS1 (a Shp2 inhibitor) delayed the development of
      dimethylbenz(a)anthracene (DMBA)-induced tumors in the rat mammary gland and also
      blocked tumor formation in MMTV-pyvt transgenic mice. Estradiol (E2) stimulated
      protein expression and phosphorylation of Shp2, and induced Shp2 binding to
      ERalpha and IGF-1R around the membrane to facilitate the phosphorylation of Erk
      and Akt in breast cancer cells MCF7. Shp2 was also involved in several biological
      effects of the extranuclear ER-initiated pathway in breast cancer cells. Specific
      inhibitors (phps1, phps4 and NSC87877) or small interference RNAs (siRNA) of Shp2
      remarkably suppressed E2-induced gene transcription (Cyclin D1 and trefoil factor
      1 (TFF1)), rapid DNA synthesis and late effects on cell growth. These results
      introduced a new mechanism for Shp2 oncogenic action and shed new light on
      extranuclear ER-initiated action in breast tumorigenesis by identifying a novel
      associated protein, Shp2, for extranuclear ER pathway, which might benefit the
      therapy of breast cancer. 

PMID- 25048204
TI  - Polymer amide as an early topology.
AB  - Hydrophobic polymer amide (HPA) could have been one of the first normal density
      materials to accrete in space. We present ab initio calculations of the
      energetics of amino acid polymerization via gas phase collisions. The initial
      hydrogen-bonded di-peptide is sufficiently stable to proceed in many cases via a
      transition state into a di-peptide with an associated bound water molecule of
      condensation. The energetics of polymerization are only favorable when the water
      remains bound. Further polymerization leads to a hydrophobic surface that is
      phase-separated from, but hydrogen bonded to, a small bulk water complex. The
      kinetics of the collision and subsequent polymerization are discussed for the low
      density conditions of a molecular cloud. This polymer in the gas phase has the
      properties to make a topology, viz. hydrophobicity allowing phase separation from
      bulk water, capability to withstand large temperature ranges, versatility of form
      and charge separation. Its flexible tetrahedral carbon atoms that alternate with
      more rigid amide groups allow it to deform and reform in hazardous conditions and
      its density of hydrogen bonds provides adhesion that would support accretion to
      it of silicon and metal elements to form a stellar dust material. 

PMID- 25048205
TI  - In vitro blood cell responsiveness to IFN-alpha predicts clinical response
      independently of IL28B in hepatitis C virus genotype 1 infected patients.
AB  - BACKGROUND: Treatment with interferon-alpha (IFN-alpha) and ribavirin
      successfully clears hepatitis C virus (HCV) infection in 50% of patients infected
      with genotype 1. Addition of NS3-4A protease inhibitors (PIs) increases response
      rates but results in additional side effects and significant economic costs.
      Here, we hypothesised that in vitro responsiveness of peripheral blood
      mononuclear cells (PBMCs) to IFN-alpha stimulation would identify patients who
      achieved sustained virological response (SVR) on dual therapy alone and thus not
      require addition of PIs. METHODS: PBMCs were isolated from HCV infected patients
      (n = 42), infected with either HCV genotype 1 or genotype 3, before commencing
      therapy and stimulated in vitro with IFN-alpha. Expression of the IFN stimulated
      genes (ISGs) PKR, OAS and MxA was measured and correlated with subsequent
      treatment response and IL28B genotype. RESULTS: Genotype 1 infected patients who
      achieved SVR had significantly higher pre-treatment expression of PKR (p =
      0.0148), OAS (p = 0.0019) and MxA (p = 0.0019) in IFN-alpha stimulated PBMCs,
      compared to genotype 1 infected patients who did not achieve SVR or patients
      infected with genotype 3, whose in vitro ISG expression did not correlate with
      clinical responsiveness. IL28B genotype (rs12979860) did not correlate with
      endogenous or IFN-alpha stimulated ISG responsiveness. CONCLUSIONS: In vitro
      responsiveness of PBMCs to IFN-alpha from genotype 1 infected patients predicts
      clinical responsiveness to dual therapy, independently of IL28B genotype. These
      results indicate that this sub-group of HCV infected patients could be identified
      pre-treatment and successfully treated without PIs, thus reducing adverse side
      effects and emergence of PI resistant virus while making significant economic
      savings.

PMID- 25048207
TI  - Enantioselective microbial synthesis of the indigenous natural product (-)-alpha
      bisabolol by a sesquiterpene synthase from chamomile (Matricaria recutita).
AB  - (-)-alpha-Bisabolol, a sesquiterpene alcohol, is a major ingredient in the
      essential oil of chamomile (Matricaria recutita) and is used in many health
      products. The current supply of (-)-alpha-bisabolol is mainly dependent on the
      Brazilian candeia tree (Eremanthus erythropappus) by distillation or by chemical
      synthesis. However, the distillation method using the candeia tree is not
      sustainable, and chemical synthesis suffers from impurities arising from
      undesirable alpha-bisabolol isomers. Therefore enzymatic synthesis of (-)-alpha
      bisabolol is a viable alternative. In the present study, a cDNA encoding (-)
      alpha-bisabolol synthase (MrBBS) was identified from chamomile and used for
      enantioselective (-)-alpha-bisabolol synthesis in yeast. Chamomile MrBBS was
      identified by Illumina and 454 sequencing, followed by activity screening in
      yeast. When MrBBS was expressed in yeast, 8 mg of alpha-bisabolol was synthesized
      de novo per litre of culture. The structure of purified alpha-bisabolol was
      elucidated as (S,S)-alpha-bisabolol [or (-)-alpha-bisabolol]. Although MrBBS
      possesses a putative chloroplast-targeting peptide, it was localized in the
      cytosol, and a deletion of its N-terminal 23 amino acids significantly reduced
      its stability and activity. Recombinant MrBBS showed kinetic properties
      comparable with those of other sesquiterpene synthases. These data provide
      compelling evidence that chamomile MrBBS synthesizes enantiopure (-)-alpha
      bisabolol as a single sesquiterpene product, opening a biotechnological
      opportunity to produce (-)-alpha-bisabolol. 

PMID- 25048206
TI  - Visits to rheumatologists for arthritis: the role of access to primary care
      physicians, geographic availability of rheumatologists, and socioeconomic status.
AB  - OBJECTIVE: This multilevel study examines access to rheumatologists for all
      arthritis and inflammatory arthritis, taking into account geographic availability
      of rheumatologists, access to primary care physicians (PCPs), and population
      characteristics (e.g., socioeconomic status [SES]). METHODS: We analyzed data
      from the population (age >=18 years) living in the 105 health planning areas in
      Ontario, Canada on visits to physicians for arthritis and musculoskeletal
      disorders. Using data from a survey of rheumatologists and Geographic Information
      System analysis, an index of geographic availability for rheumatologists was
      calculated, incorporating distance between the population and rheumatologist
      locations and the number of hours per week of rheumatologist care. Multilevel
      Poisson regression was used to examine factors associated with the rates of
      rheumatology visits for inflammatory arthritis and all arthritis. RESULTS:
      Controlling for age and sex, the rheumatologist availability index was associated
      with visit rates for all arthritis, but not inflammatory arthritis. Patients
      living in areas with low access to PCPs or low SES were less likely to have
      office visits to rheumatologists for all arthritis and inflammatory arthritis.
      CONCLUSION: Besides potential deficiencies in rheumatology provision, there may
      be access barriers to rheumatology services, particularly for populations with
      low access to PCPs or low SES. This is of special concern for patients with
      inflammatory arthritis for whom rheumatologist care is necessary. In developing
      models of care for arthritis, this study points to the need to pay attention to
      areas with low PCP resources and areas of low SES, as well as the location and
      amount of rheumatology services available.

PMID- 25048208
TI  - Vulgatibacter incomptus gen. nov., sp. nov. and Labilithrix luteola gen. nov.,
      sp. nov., two myxobacteria isolated from soil in Yakushima Island, and the
      description of Vulgatibacteraceae fam. nov., Labilitrichaceae fam. nov. and
      Anaeromyxobacteraceae fam. nov.
AB  - Two myxobacterial strains (designated B00001(T) and B00002(T)) were isolated from
      forest soil samples collected from Yakushima Island, Kagoshima, Japan.
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains
      B00001(T) and B00002(T) respectively formed independent branches within the
      suborders Cystobacterineae and Sorangiineae and were most closely related to
      Cystobacter armeniaca DSM 14710(T) (90.4% similarity) and Byssovorax cruenta DSM
      14553(T) (91.3%). Neither strain showed typical features of myxobacteria such as
      bacteriolytic action or fruiting body formation, but both had high DNA G+C
      contents (66.3-68.3 mol%). Swarming motility was observed in strain B00002(T)
      only. Cells of both strains were vegetative, chemoheterotrophic, mesophilic,
      strictly aerobic, Gram-negative, motile rods, and both strains exhibited esterase
      lipase (C8), leucine arylamidase, naphthol-AS-BI-phosphohydrolase and beta
      galactosidase activities. Strain B00001(T) contained MK-7 as the predominant
      respiratory quinone and the major fatty acid was iso-C15:0. In contrast, strain
      B00002(T) contained MK-8 as the major cellular quinone and the major fatty acids
      were C16 : 1omega5c and iso-C17 : 0. Based on the phenotypic and genotypic data
      presented, strains B00001(T) and B00002(T) represent novel genera and species,
      for which we propose the names Vulgatibacter incomptus gen. nov., sp. nov. and
      Labilithrix luteola gen. nov., sp. nov., respectively. The type strains of
      Vulgatibacter incomptus and Labilithrix luteola are B00001(T) ( = NBRC 109945(T)
      = DSM 27710(T)) and B00002(T) ( = NBRC 109946(T) = DSM 27648(T)), respectively.
      The new genera are assigned to the new families Vulgatibacteraceae fam. nov. and
      Labilitrichaceae fam. nov., respectively. In addition, Anaeromyxobacteraceae fam.
      nov., is proposed to accommodate the genus Anaeromyxobacter, which is related to
      the genus Vulgatibacter.

PMID- 25048209
TI  - Psychroflexus salarius sp. nov., isolated from Gomso salt pan.
AB  - A taxonomic study was carried out on a novel bacterial strain, designated
      MIC1008(T), which was isolated from the Gomso salt pan, located in Buan County,
      Korea. Cells were Gram-stain-negative, aerobic, non-motile and moderately
      halophilic rods, 0.2-0.4 um wide and 0.7-1.2 um long. The optimum temperature and
      pH for growth were 25  degrees C and pH 6.5-8.5, respectively. Catalase and
      oxidase activities were positive. Carotenoid pigments were produced. Comparison
      of 16S rRNA gene sequences indicated that the isolate belonged to the genus
      Psychroflexus, with Psychroflexus halocasei WCC 4520(T) as its closest relative,
      with a 16S rRNA gene sequence similarity of 95.4%. The isolate contained iso
      C15:0, iso-C15:1 G, iso-C17:0 3-OH, anteiso-C15:0 and iso-C15:0 3-OH as the major
      fatty acids and menaquinone MK-6 as the isoprenoid quinone. The major polar lipid
      profile of strain MIC1008(T) revealed the presence of phosphatidylethanolamine,
      an unidentified aminolipid and two unidentified lipids. The DNA G+C content of
      the isolate was 32.9 mol%. On the basis of the evidences presented, it is
      concluded that strain MIC1008(T) represents a novel species of the genus
      Psychroflexus within the family Flavobacteriaceae, for which the name
      Psychroflexus http://dx.doi.org/10.1601/nm.8182 salarius sp. nov. is proposed.
      The type strain is MIC1008(T) ( = KACC 17063(T) = DSM 25661(T)).

PMID- 25048210
TI  - Tangfeifania diversioriginum gen. nov., sp. nov., a representative of the family
      Draconibacteriaceae.
AB  - A novel Gram-stain-negative, facultatively anaerobic, catalase- and oxidase
      positive, non-motile and pink-pigmented bacterium, designated G22(T), was
      isolated from Gahai, a saltwater lake in Qinghai province, China. Optimal growth
      occurred at 33-35  degrees C, pH 7.0-7.5, and in the presence of 2-4% (w/v) NaCl.
      The DNA G+C content was 40.0 mol%. The major polar lipids were
      phosphatidylethanolamine and three unknown lipids. The predominant cellular fatty
      acids were iso-C15:0, anteiso-C15:0, iso-C17:0 3-OH and iso-C15:0 3-OH, and MK-7
      was the main respiratory quinone. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain G22(T) fell within the class Bacteroidia. Its
      closest phylogenetic neighbour was the recently described species
      Draconibacterium orientale, the sole member of the family Draconibacteriaceae,
      with merely 90.04% sequence similarity. On the basis of phenotypic,
      chemotaxonomic and phylogenetic evidence observed, a novel species in a new
      genus, Tangfeifania diversioriginum gen. nov., sp. nov., is proposed within the
      family Draconibacteriaceae. The type strain is G22(T) ( = CICC 10587(T) =DSM
      27063(T)).

PMID- 25048211
TI  - Pseudopelagicola gijangensis gen. nov., sp. nov., isolated from the sea squirt
      Halocynthia roretzi.
AB  - A Gram-stain-negative, aerobic, non-motile, rod-shaped bacterial strain,
      designated YSS-7(T), was isolated from a sea squirt (Halocynthia roretzi)
      collected from the South Sea of South Korea. Strain YSS-7(T) grew optimally at 25
      degrees C, at pH 7.0-8.0 and in the presence of 2.0% (w/v) NaCl. Phylogenetic
      trees based on 16S rRNA gene sequences revealed that strain YSS-7(T) clustered
      with the type strains of Pelagicola litoralis, Planktotalea frisia,
      Pacificibacter maritimus and Roseovarius marinus. Strain YSS-7(T) exhibited the
      highest 16S rRNA gene sequence similarity (97.7%) to the type strain of
      Pelagicola litoralis and sequence similarity of more than 96.0% to the type
      strains of some other species. Strain YSS-7(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 YSS-7(T) were phosphatidylcholine,
      phosphatidylglycerol, an unidentified aminolipid and an unidentified lipid. The
      fatty acid and polar lipid profiles of strain YSS-7(T) were different from those
      of the type strains of phylogenetically related species. The DNA G+C content of
      strain YSS-7(T) was 55.5 mol%. Other phenotypic properties demonstrated that
      strain YSS-7(T) is distinguished from phylogenetically related species. On the
      basis of the data presented, strain YSS-7(T) is considered to represent a novel
      genus and species, for which the name Pseudopelagicola gijangensis gen. nov., sp.
      nov. is proposed. The type strain of Pseudopelagicola gijangensis is YSS-7(T) ( =
      KCTC 42049(T) = CECT 8540(T)).

PMID- 25048212
TI  - Description of Micrococcus aloeverae sp. nov., an endophytic actinobacterium
      isolated from Aloe vera.
AB  - A yellow Gram-stain-positive, non-motile, non-endospore -forming, spherical
      endophytic actinobacterium, designated strain AE-6(T), was isolated from the
      inner fleshy leaf tissues of Aloe barbadensis (Aloe vera) collected from Pune,
      Maharashtra, India. Strain AE-6(T) grew at high salt concentrations [10% (w/v)
      NaCl], temperatures of 15-41  degrees C and a pH range of 5-12. It showed highest
      (99.7%) 16S rRNA gene sequence similarity with Micrococcus yunnanensis YIM
      65004(T) followed by Micrococcus luteus NCTC 2665(T) (99.6%) and Micrococcus
      endophyticus YIM 56238(T) (99.0%). Ribosomal protein profiling by MALDI-TOF/MS
      also showed it was most closely related to M. yunnanensis YIM 65004(T) and M.
      luteus NCTC 2665(T). Like other members of the genus Micrococcus, strain AE-6(T)
      had a high content of branched chain fatty acids (iso-C15:0 and anteiso-C15:0).
      MK-8(H2) and MK-8 were the predominant isoprenoid quinones. Cell wall analysis
      showed an 'A2 L-Lys-peptide subunit' type of peptidoglycan and ribose to be the
      major cell wall sugar. The DNA G+C content was 70 mol%. Results of DNA-DNA
      hybridization of AE-6(T) with its closest relatives from the genus Micrococcus
      produced a value of less than 70%. Based on the results of this study, strain AE
      6(T) could be clearly differentiated from other members of the genus Micrococcus.
      We propose that it represents a novel species of the genus Micrococcus and
      suggest the name Micrococcus aloeverae sp. nov., with strain AE-6(T) ( = MCC
      2184(T) = DSM 27472(T)) as the type strain of the species.

PMID- 25048213
TI  - Sphingobacterium paludis sp. nov., isolated from wetland soil.
AB  - A novel Gram-stain-negative bacteria, designated S37(T), was isolated from soil
      of the Xixi wetland, Zhejiang province, China. Cells of strain S37(T) were
      aerobic, non-motile rods. Growth occurred at 10-37  degrees C (optimum, 25 
      degrees C), pH 5.0-9.7 (optimum, pH 7.5) and with 0-6% (w/v) NaCl (optimum,
      0.5%). Based on 16S rRNA gene sequence analysis, strain S37(T) was found to be a
      member of the genus Sphingobacterium and shared highest similarity with
      Sphingobacterium composti 4M24(T) (95.78%). The major fatty acids were summed
      feature 3 (iso-C15:0 2-OH and/or C16:1omega7c), iso-C15:0 and iso-C17:0 3-OH, and
      the DNA G+C content was 43.8 mol%. The predominant respiratory quinone was MK-7.
      Based on its phenotypic and chemotaxonomic characteristics and phylogenetic data,
      strain S37(T) represents a novel species of the genus Sphingobacterium, for which
      the name Sphingobacterium paludis sp. nov. (type strain S37(T) = CGMCC 1.12801(T)
      = NBRC 110386(T)) is proposed.

PMID- 25048214
TI  - Characterization of an Ebosin derivative produced by heterologous gene
      replacement in Streptomyces sp. 139.
AB  - BACKGROUND: Ebosin is a novel exopolysaccharide (EPS) produced by Streptomyces
      sp. 139 and evidenced to possess an anti-rheumatic arthritis activity in vivo.
      The Ebosin biosynthesis gene cluster (ste) consists of 27 ORFs and ste7 has
      previously been demonstrated to code for a fucosyltransferase, which plays an
      essential role in the formation of repeating sugar units during Ebosin
      production. Aiming to generate derivatives of Ebosin for better activity, we
      replaced ste7 with a gene encoding for a glucosyltransferase (gtf) from
      Streptococcus thermophilus. RESULTS: This alteration resulted in a novel Ebosin
      derivative (EPS-7 g) with its monosaccharide composition dramatically changed,
      especially in the proportion of glucose which increased from 1.1% (Ebosin) to
      84.01% (EPS-7 g). In an ELISA analysis, EPS-7 g exhibited a higher binding
      activity for IL-1R, as a competitor of interleukin-1, than that of Ebosin. It
      also exhibited a higher inhibitory effect on the activity of IL-1beta-converting
      enzyme and production of IL-1beta in fibroblast-like synoviocytes (FLS). In
      addition, experiments with acute inflamed mice induced by croton oil showed a
      significantly higher anti-inflammatory activity of EPS-7 g compared with Ebosin.
      CONCLUSIONS: The new Ebosin derivative EPS-7 g is more bioactive than Ebosin
      evaluated by a series of experiments. This is the first report demonstrating a
      modification of EPS structure via heterologous gene replacement in Streptomyces.

PMID- 25048215
TI  - RNAi-mediated TCR knockdown prevents autoimmunity in mice caused by mixed TCR
      dimers following TCR gene transfer.
AB  - Genetically modified T cells that express a transduced T cell receptor (TCR)
      alpha/beta heterodimer in addition to their endogenous TCR are used in clinical
      studies to treat cancer. These cells express two TCR-alpha and two TCR-beta
      chains that do not only compete for CD3 proteins but also form potentially self
      reactive mixed TCR dimers, composed of endogenous and transferred chains. To
      overcome these deficits, we developed an RNAi-TCR replacement vector that
      simultaneously silences the endogenous TCR and expresses an RNAi-resistant TCR.
      Transduction of the virus-specific P14 TCR without RNAi resulted in unequal P14
      TCR-alpha and -beta chain surface levels, indicating heterodimerization with
      endogenous TCR chains. Such unequal expression was also observed following TCR
      gene optimization. Equal surface levels of the introduced TCR chains were however
      achieved by silencing the endogenous TCR. Importantly, all mice that received
      cells transduced with the native or optimized P14 TCR developed lethal TCR gene
      transfer-induced graft-versus-host-disease (TI-GVHD) due to formation of mixed
      TCR dimers. In contrast, TI-GVHD was almost completely prevented when using the
      RNAi-TCR replacement vector. Our data demonstrate that RNAi-assisted TCR
      replacement reduces the formation of mixed TCR dimers, and thereby significantly
      reduces the risk of TI-GVHD in TCR gene therapy. 

PMID- 25048216
TI  - Muscle and heart function restoration in a limb girdle muscular dystrophy 2I
      (LGMD2I) mouse model by systemic FKRP gene delivery.
AB  - Mutations in fukutin-related protein (FKRP) gene cause a wide spectrum of disease
      phenotypes including the mild limb-girdle muscular dystrophy 2I (LGMD2I), the
      severe Walker-Warburg syndrome, and muscle-eye-brain disease. FKRP deficiency
      results in alpha-dystroglycan (alpha-DG) hypoglycosylation in the muscle and
      heart, which is a biochemical hallmark of dystroglycanopathies. To study gene
      replacement therapy, we generated and characterized a new mouse model of LGMD2I
      harboring the human mutation leucine 276 to isoleucine (L276I) in the mouse
      alleles. The homozygous knock-in mice (L276I(KI)) mimic the classic late onset
      phenotype of LGMD2I in both skeletal and cardiac muscles. Systemic delivery of
      human FKRP gene by AAV9 vector in the L276I(KI) mice, at either neonatal age or
      at the age of 9 months, rendered body wide FKRP expression and restored
      glycosylation of alpha-DG in both skeletal and cardiac muscles. FKRP gene therapy
      ameliorated dystrophic pathology and cardiomyopathy such as muscle degeneration,
      fibrosis, and myofiber membrane leakage, resulting in restoration of muscle and
      heart contractile functions. Thus, these results demonstrated that the treatment
      based on FKRP gene replacement was effective. 

PMID- 25048218
TI  - The urgent need for nurse practitioners to lead antimicrobial stewardship in
      ambulatory health care.

PMID- 25048217
TI  - Vector design Tour de Force: integrating combinatorial and rational approaches to
      derive novel adeno-associated virus variants.
AB  - Methodologies to improve existing adeno-associated virus (AAV) vectors for gene
      therapy include either rational approaches or directed evolution to derive capsid
      variants characterized by superior transduction efficiencies in targeted tissues.
      Here, we integrated both approaches in one unified design strategy of "virtual
      family shuffling" to derive a combinatorial capsid library whereby only variable
      regions on the surface of the capsid are modified. Individual sublibraries were
      first assembled in order to preselect compatible amino acid residues within
      restricted surface-exposed regions to minimize the generation of dead-end
      variants. Subsequently, the successful families were interbred to derive a
      combined library of ~8 * 10(5) complexity. Next-generation sequencing of the
      packaged viral DNA revealed capsid surface areas susceptible to directed
      evolution, thus providing guidance for future designs. We demonstrated the
      utility of the library by deriving an AAV2-based vector characterized by a 20
      fold higher transduction efficiency in murine liver, now equivalent to that of
      AAV8. 

PMID- 25048219
TI  - The sodium channel isoform transition at developing nodes of Ranvier in the
      peripheral nervous system: dependence on a Genetic program and myelination
      induced cluster formation.
AB  - Among sodium channel isoforms, Nav 1.6 is selectively expressed at nodes of
      Ranvier in both the CNS and the PNS. However, non-Nav 1.6 isoforms such as Nav
      1.2 are also present at the CNS nodes in early development but gradually diminish
      later. It has been proposed that myelination is part of a glia-neuron signaling
      mechanism that produces this change in nodal isoform expression. The present
      study used isoform-specific antibodies to demonstrate that, in the PNS, four
      other neuronal sodium channel isoforms were also clustered at nodes in early
      development but eventually disappeared during maturation. To study possible roles
      of myelination in such transitions, we investigated the nodal expression of
      selected isoforms in the sciatic nerve of the transgenic mouse
      Oct6(DeltaSCE/betageo) , whose PNS myelination is delayed in the first postnatal
      week but eventually resumes. We found that delayed myelination retarded the
      formation of nodal channel clusters and altered the expression-elimination
      patterns of sodium channel isoforms, resulting in significantly reduced
      expression levels of non-Nav 1.6 isoforms in such delayed nodes. However, delayed
      myelination did not significantly affect the gene expression, protein synthesis,
      or axonal trafficking of any isoform studied. Rather, we found evidence for a
      developmentally programmed increase in neuronal Nav 1.6 expression with constant
      or decreasing neuronal expression of other isoforms that were unaffected by
      delayed myelination. Thus our results suggest that, in the developmental isoform
      switch of the PNS, myelination does not play a signaling role as that proposed
      for the CNS but rather serves only to form nodal clusters from existing isoform
      pools.

PMID- 25048220
TI  - Effects of transgenic soybean on growth and phosphorus acquisition in mixed
      culture system.
AB  - Transgenic soybean plants overexpressing the Arabidopsis purple acid phosphatase
      gene AtPAP15 (OXp) or the soybean expansin gene GmEXPB2 (OXe) can improve
      phosphorous (P) efficiency in pure culture by increasing Apase secretion or
      changing root morphology. In this study, soybean-soybean mixed cultures were
      employed to illuminate P acquisition among plants in mixed stands of transgenic
      and wild-type soybean. Our results showed that transgenic soybean plants were
      much more competitive, and had greater growth and P uptake than wild-type soybean
      in mixed culture in both low P calcareous and acid soils. Furthermore, OXe plants
      had an advantage in calcareous soils when mixed with OXp, whereas the latter
      performed much better in acid soils. In soybean-maize mixed culture, transgenic
      soybean had no impact on maize growth compared to controls in both acid and
      calcareous soils with different P conditions. As for soybean in mixed culture,
      OXp plants had no significant advantages regardless of P availability or soil
      type, while P efficiency improved in OXe in calcareous soils compared to
      controls. These results imply that physiological traits could be easily affected
      by the mixed maize. Transgenic soybean plants with enhanced root traits had more
      competitive advantages than those with improved root physiology in mixed culture.

PMID- 25048221
TI  - Comparison of the genomes and transcriptomes associated with the different
      protease secretions of Aspergillus oryzae 100-8 and 3.042.
AB  - Aspergillus oryzae is used to produce traditional fermented foods and beverages.
      A. oryzae 3.042 produces a neutral protease and an alkaline protease but rarely
      an acid protease, which is unfavourable to soy-sauce fermentation. A. oryzae 100
      8 was obtained by N(+) ion implantation mutagenesis of A. oryzae 3.042, and the
      protease secretions of these two strains are different. Sequencing the genome of
      A. oryzae 100-8 and comparing it to the genomes of A. oryzae 100-8 and 3.042
      revealed some differences, such as single nucleotide polymorphisms, nucleotide
      deletion or insertion. Some of these differences may reflect the ability of A.
      oryzae to secrete proteases. Transcriptional sequencing and analysis of the two
      strains during the same growth processes provided further insights into the genes
      and pathways involved in protease secretion. 

PMID- 25048222
TI  - Epitope mapping of the infectious hematopoietic necrosis virus glycoprotein by
      flow cytometry.
AB  - The glycoprotein of infectious hematopoietic necrosis virus was truncated to ten
      overlapping fragments. All fragments were displayed on the inner membrane of the
      Escherichia coli periplasm. After disruption of the outer membrane, spheroplasts
      that had anchored with the glycoprotein fragment were incubated with an anti
      glycoprotein polyclonal antibody. Prey pairs were detected and quantitated by
      flow cytometry with all fragments but one, G2, reacting with the polyclonal
      antibody. The antigenicity of all ten fragments was analyzed using conventional
      methods, and epitopes were localized in all fragments, except for G2 and were
      consistent with FCM analysis. Antigenicity of purified glycoprotein fusion
      proteins was confirmed by western blotting and ELISA. This method provides a
      rapid, quantitative and simple strategy for identifying linear B cell epitopes of
      a given protein. 

PMID- 25048223
TI  - Enhanced production techniques, properties and uses of coenzyme Q10.
AB  - Coenzyme Q10 (CoQ10) is an essential component of the respiratory chain which
      produces ATP. It is formed from the conjugation of a benzoquinone ring with a
      hydrophobic isoprenoid chain. Efforts on the production of CoQ10 by
      microorganisms focus on the development of potent strains by conventional
      mutagenesis and metabolic engineering especially in Escherichia coli, analysis
      and modification of the key metabolic pathways and optimization of fermentation
      strategies. CoQ10 has excellent antioxidant properties and is beneficial in the
      treatment of several human diseases. The present review covers the current
      strategies used to improve and/or engineer CoQ10 production in microbes, the
      yields obtained in light of the current knowledge on the biosynthesis of this
      molecule. It also highlights the medical effects of CoQ10. 

PMID- 25048224
TI  - Characterization of industrially-valuable xylano-pectinolytic enzymes produced
      concurrently by a novel isolate of Bacillus pumilus.
AB  - Xylanase and polygalacturonase were concurrently produced by a novel alkalo
      thermotolerant Bacillus pumilus AJK. They were purified and characterized to
      evaluate their potential for various industrial applications. Xylanase was
      purified to 19-fold with 67 % recovery and polygalacturonase up to 23-fold with
      75 % recovery. Existence of multiple forms of xylanase was indicated by its
      elution-profile through Sephadex G-100 as two peaks, xylanase-I and xylanase-II,
      with molecular weights of ~24.5 and ~13 kDa, respectively, and by the presence of
      two pH optima, one at pH 6.0 and other at pH 8.5. The molecular weight of
      polygalacturonase was ~40 kDa by gel-filtration chromatography. Zymographic
      studies confirmed the presence of seven isozymic forms of xylanase. Xylanase and
      polygalacturonase are stable over a broad range of pH and temperature. 

PMID- 25048225
TI  - Enzymatic acylation of flavonoid glycosides by a carbohydrate esterase of family
      16.
AB  - The acetyl esterase of Trichoderma reesei belonging to carbohydrate esterase (CE)
      family 16 catalyzes transacylations to carbohydrate moieties of flavonoid
      glycosides, esculin and rutin. The enzyme recognizes as acyl donors vinyl esters
      of short carboxylic acids. Esculin was acylated at position 3 of the glucosyl
      residue in aqueous solutions saturated with vinyl acetate and vinyl propionate.
      The yields of esculin monoacetate and monopropionate of esculin in aqueous medium
      (esculin 40 mM, enzyme 40 ug/ml, 40  degrees C, 3 days) were 67 and 55 %,
      respectively. Replacement of water by 2-propanol was required for a similar
      acylation of rutin at 4 mM concentration. The yields of rutin monoacetate and
      propionate were 60 and 30 %, respectively. The results indicate that the enzyme
      could be used for an easy modification of solubility and hydrophobicity of
      glycosylated compounds, including drugs and functional food additives. 

PMID- 25048226
TI  - Metabolic engineering of Escherichia coli for poly(3-hydroxypropionate)
      production from glycerol and glucose.
AB  - A new poly(3-hydroxypropionate) (P3HP) biosynthetic pathway employing beta
      alanine as an intermediate from an inexpensive carbon source was developed in
      recombinant Escherichia coli. After a series of systematic optimization, the
      genes for L-aspartate decarboxylase and its maturation factor (panD and panM,
      from E. coli), beta-alanine-pyruvate transaminase (pp0596, from Pseudomonas
      putida), 3-hydroxy acid dehydrogenase and 3-hydroxypropionyl-CoA synthase (ydfG
      and prpE respectively, from E. coli), and polyhydroxyalkanoate synthase (phaC1,
      from Cupriavidus necator) were cloned and expressed in E. coli. Under shake-flask
      conditions, the recombinant strain produced 0.5 g P3HP l(-1) from glycerol and
      glucose, up to 10.2 % of CDW. Though the content of P3HP was low, this pathway
      has some advantages over other reported pathways, such as being redox neutral,
      does not require any coenzyme, and can use a wide range of carbon sources. 

PMID- 25048227
TI  - Proteomic analysis of the response to NaCl stress of Lactobacillus bulgaricus.
AB  - Lactobacillus bulgaricus is commonly used in dairy products as a starter culture.
      Its viability during freeze-drying is of commercial interest. Here a significant
      (p < 0.05) improvement in survival rate of L. bulgaricus ATCC 11842 was achieved
      during freeze-drying when it was prestressed with 2 % (w/v) NaCl for 2 h in the
      late growth phase. To understand the mechanism of this stress-related viability
      improvement in L. bulgaricus, protein synthesis was analyzed by 2D difference gel
      electrophoresis. Nine protein spots were significantly altered by NaCl and were
      subsequently identified by peptide mass fingerprinting. The functions of the
      proteins included stress-related protein synthesis, amino acid biosynthesis,
      nucleotide biosynthesis, sugar metabolism, transport systems, and vitamin
      biosynthesis. These findings provide a considerable background regarding the NaCl
      stress response of L. bulgaricus. 

PMID- 25048228
TI  - C-20 Ketone reduction of hydrocortisone by Fusarium solani and Aspergillus
      ochraceus.
AB  - The biotransformation of hydrocortisone (1) by Fusarium solani and Aspergillus
      ochraceus was investigated for the first time. After 10 days at 30  degrees C,
      just one metabolite was produced by both fungi: 11beta, 17alpha, 20beta, 21
      tetrahydroxypregn-4-en-3-one (2) established on the basis of spectroscopic data.
      The reaction was reduction of the 20-carbonyl group. Time course study determined
      by HPLC showed 60 and 45 % yield for the metabolite by F. solani and A.
      ochraceus, respectively. 

PMID- 25048230
TI  - Characterization of beta-xylosidase from Thermoanaerobacterium
      thermosaccharolyticum and its application to the production of ginsenosides Rg1
      and Rh 1 from notoginsenosides R 1 and R 2.
AB  - beta-Xylosidase from Thermoanaerobacterium thermosaccharolyticum was purified by
      His-trap affinity chromatography giving a specific activity of 5.15 U mg(-1).
      From gel-filtration chromatography, the purified enzyme was a tetramer with a
      total molecular mass of 245 kDa. Maximal enzyme activity using o-nitrophenyl(NP)
      beta-D-xylopyranoside was at pH 6.5 and 60  degrees C, with a half-life of 50 h.
      The enzyme had highest activity for oNP-beta-D-xylopyranoside among aryl
      glycosides, and was only active for notoginsenosides R1 and R2 amongst various
      ginsenosides. beta-Xylosidase completely converted 2 g notoginsenosides R1 and R2
      l(-1) to 1.69 g ginsenoside Rg1 l(-1) and 1.63 g ginsenoside Rh1 l(-1) in 4 and
      18 h, respectively, with molar conversion yields of 100 % and specific
      productivities of 0.21 and 0.05 g g-enzyme(-1) h(-1), respectively. To our
      knowledge, this is the first report on the enzymatic production of ginsenosides
      Rg1 and Rh1 from notoginsenosides R1 and R2. 

PMID- 25048229
TI  - Putative signal peptides of two BURP proteins can direct proteins to their
      destinations in tobacco cell system.
AB  - Plant-specific BURP family proteins have a diverse subcellular localization with
      different functions. However, only limited studies have investigated the
      functions of their different domains. In the present study, the role of the N
      terminal putative signal peptide in protein subcellular localization was
      investigated using a tobacco cell system. The results showed that SALI3-2 was
      present in vacuoles, whereas AtRD22 was directed to the apoplast. The N-terminal
      putative signal peptides of both proteins were confirmed to be the essential and
      critical domains for targeting the proteins to their destinations. We also
      demonstrate that the expression and accumulation of mGFP in tobacco cells was
      increased when mGFP was fused to the putative signal peptide of SALI3-2. The
      findings offer the potential application of this short peptide in protein
      production in plants. 

PMID- 25048231
TI  - Increased mycelial biomass production by Lentinula edodes intermittently
      illuminated by green light emitting diodes.
AB  - Fungi possess a range of light receptors to regulate metabolism and
      differentiation. To study the effect of light on Lentinula edodes (the shiitake
      mushroom), mycelial cultures were exposed to blue, green, and red fluorescent
      lights and light-emitting diodes, as well as green laser light. Biomass
      production, morphology, and pigment production were evaluated. Exposure to green
      light at intervals of 1 min/d at 0.4 W/m(2) stimulated biomass production by 50
      100 %, depending on the light source. Light intensities in excess of 1.8 W/m(2)
      or illumination longer than 30 min/d did not affect biomass production.
      Carotenoid production and morphology remained unaltered during increased biomass
      production. These observations provide a cornerstone to the study of
      photoreception by this important fungus. 

PMID- 25048232
TI  - Identification and characterization of a novel phage display-derived peptide with
      affinity for human brain metastatic breast cancer.
AB  - A novel peptide, BRBP1 (MYPWTEPSYLSN), was identified using an in vitro phage
      biopanning strategy against human brain-seeking breast carcinoma cells (231-BR
      cells).The peptide-phage clone, BRBP1-M13 displaying BRBP1 sequence, specifically
      bound to 231-BR cells and the binding could be competitively abolished by BRBP1.
      In vivo distribution studies showed that BRBP1-M13 preferentially homed to the
      231-BR tumors. Fluorescently-labeled BRBP1, BRBP1-K(5-TAMRA), preferentially
      bound to 231-BR cells in a dose-dependent and energy-dependent manner and it was
      efficiently internalized into the cells after 2 h incubation. Near-infrared
      fluorophores imaging demonstrated the accumulation of Cy5.5-conjugated BRBP1
      peptide in the tumors in vivo. Thus, BRBP1 is a promising peptide binding to
      human brain metastatic breast cancer and it may be applied to targeted delivery
      of cytotoxic agents to the intended tumor. 

PMID- 25048233
TI  - Type III polyketide synthase is involved in the biosynthesis of protocatechuic
      acid in Aspergillus niger.
AB  - Genomic studies have shown that not only plants but also filamentous fungi
      contain type III polyketide synthases. To study the function of type III
      polyketide synthase (AnPKSIII) in Aspergillus niger, a deletion strain
      (delAnPKSIII) and an overexpression strain (oeAnPKSIII) were constructed in A.
      niger MA169.4, a derivative of the wild-type (WT) A. niger ATCC 9029 that
      produces large quantities of gluconic acid. Alterations in the metabolites were
      analyzed by HPLC when the extract of the overexpression strain was compared with
      extracts of the WT and deletion strains. Protocatechuic acid (PCA; 3,4
      dihydroxybenzoic acid, 3.2 mg/l) was isolated and identified as the main product
      of AnPKSIII when inductively expressed in A. niger MA169.4. The molecular weight
      of PCA was 154.1 (m/z 153.1 [M-H](-)), was detected by ESI-MS in the negative
      ionization mode, and (1)H and (13)C NMR data confirmed its structure. 

PMID- 25048234
TI  - Biotechnological approach towards a highly efficient production of natural
      prostaglandins.
AB  - Prostaglandins (PGs) act as potent local hormones in nearly all tissues of the
      human body and are used for various medical applications. Heterologous expression
      of PG endoperoxide H-synthase from the alga, Gracilaria vermiculophylla, into E.
      coli and the application of this strain in biotransformation experiments resulted
      in a highly efficient conversion of arachidonic acid (ARA) yielding up to 130 mg
      natural PGs l(-1) in a laboratory scale approach. Detailed analyses of the
      products and production kinetics were performed, confirming a rapid conversion of
      ARA to PGs. 

PMID- 25048235
TI  - Cloning and starch degradation profile of maltotriose-producing amylases from
      Streptomyces species.
AB  - The end products from starch hydrolysis by amylases have important applications
      in various industries. Here, two amylases derived from two Streptomyces species
      that hydrolyze soluble starch from potato produced maltotriose as the primary
      maltooligosaccharide product. The genes, annotated as putative glycoside
      hydrolases, were cloned and expressed in Streptomyces lividans. These amylases
      displayed hydrolysis activity from pH 3 to 9.5 and were not affected by Ca(2+.)
      Optimal production of maltotriose was between 20 and 30  degrees C at pH 6.5. At
      the optimal temperature, both amylases produced maltotriose-rich end products
      rather than either maltose or maltotetraose. 

PMID- 25048236
TI  - Cytotoxic effect of the biotechnologically-derived justicidin B on human lymphoma
      cells.
AB  - Purpose of work: The study was aimed to assess the antineoplastic activity of
      justicidin B in vitro and to search for its general toxicological profile in
      vivo. The anti-neoplastic activity of the arylnaphthalene lignin, justicidin B,
      was assessed in a panel of human lymphoma cell lines and compared with etoposide
      as a reference compound. A screening of the cytotoxicity after 24, 48 and 72 h
      exposure was performed by the MTT-dye reduction assay. Dose- and time-dependent
      cytotoxic effect was observed and the IC50 values ranged from 0.17 uM (RPMI-8226,
      72 h) to 183 uM (U-266, 24 h) and more than 200 uM (HD-MY-Z, 24 and 48 h).
      Activation of caspase 3 and 8 was involved in the induction of programmed cell
      death in DOHH-2 cell line. NF-kappaB modulation occurred in DOHH-2 and HH cells.
      The general toxicity in mice after i.p. injection was also tested. The highest
      applied dose (50 mg/kg = 137.25 uM) did not show any toxicity. Justicidin B
      possesses definite and potent selective antineoplastic activity, related to its
      ability to induce programmed cell death in NHL-derived human cell lines at
      concentrations that can be reached in mice without toxicity. 

PMID- 25048237
TI  - Enhanced production of poly-gamma-glutamic acid by a newly-isolated Bacillus
      subtilis.
AB  - Application of poly-gamma-glutamic acid (gamma-PGA), an unusual macromolecular
      anionic polypeptide, is limited due to the high cost associated with its low
      productivity. Screening bacterial strains to find a more efficient producer is
      one approach to overcome this limitation. Strain MJ80 was isolated as a gamma-PGA
      producer among 1,500 bacterial colonies obtained from soil samples. It was
      identified as Bacillus subtilis, based on the biochemical and morphological
      properties and 16S rDNA gene sequencing. It produced gamma-PGA from both glutamic
      acid and soybean powder, identifying it as a facultative glutamic acid
      metabolizing bacterium. After optimization of its culture conditions, B. subtilis
      MJ80 showed gamma-PGA productivity of 75.5 and 68.7 g/l in 3 and 300 l jar
      fermenters for 3 days cultivation, respectively, the highest productivity
      reported to date, suggesting MJ80 to be a promising strain for gamma-PGA
      production. 

PMID- 25048238
TI  - Purification and characterization of a novel cis-epoxysuccinate hydrolase from
      Klebsiella sp. that produces L(+)-tartaric acid.
AB  - A strain of Klebsiella sp. BK-58 that produces cis-epoxysuccinate was screened
      and identified. This novel enzyme hydrolyzes cis-epoxysuccinate to L(+)-tartaric
      acid and was purified to homogeneity. Its molecular mass was 30.1 kDa determined
      by MALDI-TOF-MS analysis. It was stable up to 50  degrees C and from pH 5 to 11
      with optima at 50  degrees C and pH 8.5. The enzyme was metal-independent and was
      strongly inhibited by 1 mM Cu(2+) and Ag(+), and 1 % (w/v) SDS. The K m , V max
      and turnover number (k cat ) values for cis-epoxysuccinate were 19.3, 2.24 mM
      min(-1) and 220 s(-1), respectively. 

PMID- 25048239
TI  - Isolation and characterization of a cryptogein-like gene from drought and salt
      treated Alternanthera philoxeroides roots.
AB  - Alligator weed, Alternanthera philoxeroides (Mart.) Grisb, is an amphibious plant
      with long thick fleshy roots that develop from adventitious roots under drought
      conditions. To clone differentially-expressed genes from the roots of A.
      philoxeroides we applied both mRNA differential display and rapid amplification
      of cDNA ends techniques. A cryptogein-like gene of A. philoxeroides, designated
      as ApCL, was cloned. On the basis of semi-quantitative RT-PCR analysis results,
      we demonstrated that the ApCL gene was upregulated under drought and salt stress
      conditions. After ApCL was transferred to Pichia pastoris GS115 and its
      resistance to drought and salt then increased by >100 %. Therefore, the ApCL gene
      of A. philoxeroides was likely involved in drought and salt tolerance responses. 

PMID- 25048240
TI  - Simultaneous enhanced catalytic activity and thermostability of a 1,3-1,4-beta
      glucanase from Bacillus amyloliqueformis by chemical modification of lysine
      residues.
AB  - The thermostablility and enzymatic activity of 1,3-1,4-beta-glucanase (BglA) from
      Bacillus amyloliquefaciens was improved by modifying five (out of 12) epsilon
      amino groups in lysine residues with nitrous acid. The optimal modification
      condition for BglA was determined as 30 mM nitrous acid at, 40  degrees C for 30
      min. The optimally-modified BglA had higher specific activity and T 50 value,
      which were 3,370 U/mg and 70  degrees C, respectively. Its half-life values at 50
      and 60  degrees C were extended and reached 58.5 and 49.5 min, respectively.
      Circular dichroism analysis showed that the secondary structures in modified BglA
      were almost the same with that of wild-type BglA. Thus, modification of lysine
      residues can simultaneously improve the activity and thermostability of beta
      glucanase which are ideal targets for further protein engineering. 

PMID- 25048241
TI  - A prepared anti-MSTN polyclonal antibody reverses insulin resistance of diet
      induced obese rats via regulation of PI3K/Akt/mTOR&FoxO1 signal pathways.
AB  - Suppression of myostatin (MSTN) is associated with skeletal muscle atrophy and
      insulin resistance. However, the mechanisms by which MSTN regulates insulin
      resistance are not well known. We have explored the signaling pathways through
      which MSTN regulates insulin resistance in diet-induced obese rats using a
      polyclonal antibody for MSTN. The anti-MSTN polyclonal antibody significantly
      improved insulin resistance and whole-body insulin sensitivity, decreased MSTN
      protein expression in muscle samples by 39% in diet-induced obese rats.
      Furthermore, the anti-MSTN polyclonal antibody significantly enhanced PI3K
      activity (140%), Akt phosphorylation (86%), GLUT4 protein expression (23%), the
      phosphorylation of mTOR (21%), and inhibited the phosphorylation of FoxO1 (57%),
      but did not affect the phosphorylation of GSK-3beta. Thus, suppression of MSTN by
      the anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced
      obesity via MSTN/PI3K/Akt/mTOR and MSTN/PI3K/Akt/FoxO1 signaling pathways.

PMID- 25048242
TI  - Frequency-dependent ultrasound-induced transformation in E. coli.
AB  - Ultrasound-enhanced gene transfer (UEGT) is continuing to gain interest across
      many disciplines; however, very few studies investigate UEGT efficiency across a
      range of frequencies. Using a variable frequency generator, UEGT was tested in E.
      coli at six ultrasonic frequencies. Results indicate frequency can significantly
      influence UEGT efficiency positively and negatively. A frequency of 61 kHz
      improved UEGT efficiency by ~70 % higher, but 99 kHz impeded UEGT to an extent
      worse than no ultrasound exposure. The other four frequencies (26, 133, 174, and
      190 kHz) enhanced transformation compared to no ultrasound, but efficiencies did
      not vary. The influence of frequency on UEGT efficiency was observed across a
      range of operating frequencies. It is plausible that frequency-dependent dynamics
      of mechanical and chemical energies released during cavitational-bubble collapse
      (CBC) are responsible for observed UEGT efficiencies. 

PMID- 25048243
TI  - Enhanced expression of recombinant elastase in Pichia pastoris through addition
      of N-glycosylation sites to the propeptide.
AB  - N-Glycosylation is a common form of protein post-translational modification in
      Pichia pastoris and greatly affects folding and secretion. The propeptide of the
      Pseudomonas aeruginosa elastase (PAE) is indispensable for proper folding and
      secretion of the enzyme. We have studied the effect of introducing N
      glycosylation sites to the propeptide of the recombinant elastase (rPAE) on its
      expression levels in P. pastoris. Addition of N-glycosylation sites to the
      propeptide at N51 or N93 enhanced rPAE production levels by 104 or 57%,
      respectively, while addition at N11 or N127 led to a 25 or 50% decrease,
      respectively. The introduced N-glycosylation sites in the propeptide at these
      four sites exerted a null effect on the N-glycosylation degree of mature rPAE.

PMID- 25048244
TI  - Recombinant plant-derived pharmaceutical proteins: current technical and economic
      bottlenecks.
AB  - Molecular pharming is a cost-effective platform for the production of recombinant
      proteins in plants. Although the biopharmaceutical industry still relies on a
      small number of standardized fermentation-based technologies for the production
      of recombinant proteins there is now a greater awareness of the advantages of
      molecular pharming particularly in niche markets. Here we discuss some of the
      technical, economic and regulatory barriers that constrain the clinical
      development and commercialization of plant-derived pharmaceutical proteins. We
      also discuss strategies to increase productivity and product quality/homogeneity.
      The advantages of whole plants should be welcomed by the industry because this
      will help to reduce the cost of goods and therefore expand the biopharmaceutical
      market into untapped sectors. 

PMID- 25048245
TI  - Purification of a recombinant histidine-tagged lactate dehydrogenase from the
      malaria parasite, Plasmodium vivax, and characterization of its properties.
AB  - Lactate dehydrogenase (LDH) of the malaria parasite, Plasmodium vivax (Pv),
      serves as a drug target and immunodiagnostic marker. The LDH cDNA generated from
      total RNA of a clinical isolate of the parasite was cloned into pRSETA plasmid.
      Recombinant his-tagged PvLDH was over-expressed in E. coli Rosetta2DE3pLysS and
      purified using Ni(2+)-NTA resin giving a yield of 25-30 mg/litre bacterial
      culture. The recombinant protein was enzymatically active and its catalytic
      efficiency for pyruvate was 5.4 * 10(8) min(-1) M(-1), 14.5 fold higher than a
      low yield preparation reported earlier to obtain PvLDH crystal structure. The
      enzyme activity was inhibited by gossypol and sodium oxamate. The recombinant
      PvLDH was reactive in lateral flow immunochromatographic assays detecting pan-
      and vivax-specific LDH. The soluble recombinant PvLDH purified using heterologous
      expression system can facilitate the generation of vivax LDH-specific monoclonals
      and the screening of chemical compound libraries for PvLDH inhibitors. 

PMID- 25048246
TI  - Vitamin A intake and risk of melanoma: a meta-analysis.
AB  - BACKGROUND: Mounting evidence from experimental and animal studies suggests that
      vitamin A may have a protective effect on melanoma, but the findings on the
      association of vitamin A intake with risk of melanoma have been inconsistently
      reported in epidemiologic studies. We attempted to elucidate the association by
      performing a meta-analysis. METHODS: Eligible studies were identified by
      searching PubMed and EMBASE databases, as well as by reviewing the references of
      retrieved publications. Summary odds ratios (OR) with corresponding 95%
      confidence interval (CI) were computed with a random-effects model. Study
      specific ORs and 95% CIs for the highest vs. lowest categories of vitamin A
      intake were pooled. RESULTS: A total of 8 case-control studies and 2 prospective
      studies comprising 3,328 melanoma cases and 233,295 non-case subjects were
      included. The summary OR for the highest compared with the lowest intake of total
      vitamin A, retinol and beta-carotene was 0.86 (95% CI = 0.59-1.25), 0.80 (95% CI
      = 0.69-0.92) and 0.87 (95%CI = 0.62-1.20), respectively. Significant
      heterogeneity was observed among studies on vitamin A and beta-carotene intake,
      but not among studies on retinol intake. Subgroup and sensitivity analyses
      confirmed these findings. There was no indication of publication bias.
      CONCLUSION: Findings from this meta-analysis suggest that intake of retinol,
      rather than of total vitamin A or beta-carotene, is significantly associated with
      reduced risk of melanoma.

PMID- 25048247
TI  - Social network sites as a mode to collect health data: a systematic review.
AB  - BACKGROUND: To date, health research literature has focused on social network
      sites (SNS) either as tools to deliver health care, to study the effect of these
      networks on behavior, or to analyze Web health content. Less is known about the
      effectiveness of these sites as a method for collecting data for health research
      and the means to use such powerful tools in health research. OBJECTIVE: The
      objective of this study was to systematically review the available literature and
      explore the use of SNS as a mode of collecting data for health research. The
      review aims to answer four questions: Does health research employ SNS as method
      for collecting data? Is data quality affected by the mode of data collection?
      What types of participants were reached by SNS? What are the strengths and
      limitations of SNS? METHODS: The literature was reviewed systematically in March
      2013 by searching the databases MEDLINE, Embase, and PsycINFO, using the Ovid and
      PubMed interface from 1996 to the third week of March 2013. The search results
      were examined by 2 reviewers, and exclusion, inclusion, and quality assessment
      were carried out based on a pre-set protocol. RESULTS: The inclusion criteria
      were met by 10 studies and results were analyzed descriptively to answer the
      review questions. There were four main results. (1) SNS have been used as a data
      collection tool by health researchers; all but 1 of the included studies were
      cross-sectional and quantitative. (2) Data quality indicators that were reported
      include response rate, cost, timeliness, missing data/completion rate, and
      validity. However, comparison was carried out only for response rate and cost as
      it was unclear how other reported indicators were measured. (3) The most targeted
      population were females and younger people. (4) All studies stated that SNS is an
      effective recruitment method but that it may introduce a sampling bias.
      CONCLUSIONS: SNS has a role in health research, but we need to ascertain how to
      use it effectively without affecting the quality of research. The field of SNS is
      growing rapidly, and it is necessary to take advantage of the strengths of this
      tool and to avoid its limitations by effective research design. This review
      provides an important insight for scholars who plan to conduct research using
      SNS.

PMID- 25048248
TI  - Matching 4.7-A XRD spacing in amelogenin nanoribbons and enamel matrix.
AB  - The recent discovery of conditions that induce nanoribbon structures of
      amelogenin protein in vitro raises questions about their role in enamel
      formation. Nanoribbons of recombinant human full-length amelogenin (rH174) are
      about 17 nm wide and self-align into parallel bundles; thus, they could act as
      templates for crystallization of nanofibrous apatite comprising dental enamel.
      Here we analyzed the secondary structures of nanoribbon amelogenin by x-ray
      diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) and tested
      if the structural motif matches previous data on the organic matrix of enamel.
      XRD analysis showed that a peak corresponding to 4.7 A is present in nanoribbons
      of amelogenin. In addition, FTIR analysis showed that amelogenin in the form of
      nanoribbons was comprised of beta-sheets by up to 75%, while amelogenin
      nanospheres had predominantly random-coil structure. The observation of a 4.7-A
      XRD spacing confirms the presence of beta-sheets and illustrates structural
      parallels between the in vitro assemblies and structural motifs in developing
      enamel. 

PMID- 25048249
TI  - Reliability estimation for single-unit ceramic crown restorations.
AB  - The objective of this study was to evaluate the potential of a survival
      prediction method for the assessment of ceramic dental restorations. For this
      purpose, fast-fracture and fatigue reliabilities for 2 bilayer (metal ceramic
      alloy core veneered with fluorapatite leucite glass-ceramic, d.Sign/d.Sign-67, by
      Ivoclar; glass-infiltrated alumina core veneered with feldspathic porcelain,
      VM7/In-Ceram Alumina, by Vita) and 3 monolithic (leucite-reinforced glass
      ceramic, Empress, and ProCAD, by Ivoclar; lithium-disilicate glass-ceramic,
      Empress 2, by Ivoclar) single posterior crown restorations were predicted, and
      fatigue predictions were compared with the long-term clinical data presented in
      the literature. Both perfectly bonded and completely debonded cases were analyzed
      for evaluation of the influence of the adhesive/restoration bonding quality on
      estimations. Material constants and stress distributions required for predictions
      were calculated from biaxial tests and finite element analysis, respectively.
      Based on the predictions, In-Ceram Alumina presents the best fast-fracture
      resistance, and ProCAD presents a comparable resistance for perfect bonding;
      however, ProCAD shows a significant reduction of resistance in case of complete
      debonding. Nevertheless, it is still better than Empress and comparable with
      Empress 2. In-Ceram Alumina and d.Sign have the highest long-term reliability,
      with almost 100% survivability even after 10 years. When compared with clinical
      failure rates reported in the literature, predictions show a promising match with
      clinical data, and this indicates the soundness of the settings used in the
      proposed predictions. 

PMID- 25048250
TI  - Longevity of posterior composite restorations: a systematic review and meta
      analysis.
AB  - The aim of this meta-analysis, based on individual participant data from several
      studies, was to investigate the influence of patient-, materials-, and tooth
      related variables on the survival of posterior resin composite restorations.
      Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines, we conducted a search resulting in 12 longitudinal studies
      of direct posterior resin composite restorations with at least 5 years' follow
      up. Original datasets were still available, including placement/failure/censoring
      of restorations, restored surfaces, materials used, reasons for clinical failure,
      and caries-risk status. A database including all restorations was constructed,
      and a multivariate Cox regression method was used to analyze variables of
      interest [patient (age; gender; caries-risk status), jaw (upper; lower), number
      of restored surfaces, resin composite and adhesive materials, and use of glass
      ionomer cement as base/liner (present or absent)]. The hazard ratios with
      respective 95% confidence intervals were determined, and annual failure rates
      were calculated for subgroups. Of all restorations, 2,816 (2,585 Class II and 231
      Class I) were included in the analysis, of which 569 failed during the
      observation period. Main reasons for failure were caries and fracture. The
      regression analyses showed a significantly higher risk of failure for
      restorations in high-caries-risk individuals and those with a higher number of
      restored surfaces. 

PMID- 25048251
TI  - An "all-green" catalytic cycle of aqueous photoionization.
AB  - Hydrated electrons are highly aggressive species that can force chemical
      transformations of otherwise unreactive molecules such as the reductive
      detoxification of halogenated organic compounds. We present the first example of
      the sustainable production of hydrated electrons through a homogeneous catalytic
      cycle driven entirely by green light (532 nm, coinciding with the maximum of the
      terrestrial solar spectrum). The catalyst is a metal complex serving as a
      "container" for a radical anion. This active center is generated from a ligand
      through quenching by a sacrificial electron donor, is shielded by the complex
      such that it stores the energy of the photon for much longer than a free radical
      anion could, and is finally ionized by another photon to regenerate the ligand
      and recover the starting complex quantitatively. The sacrificial donor can be a
      bioavailable reagent such as ascorbic acid. 

PMID- 25048252
TI  - Temporal and thermal variations in site-specific thermoregulatory sudomotor
      thresholds: precursor versus discharged sweat production.
AB  - Temporal and thermal differences between the initiation of precursor, eccrine
      sweat and its surface discharge were investigated during passive heating.
      Sudomotor activity was evaluated using electrodermal (precursor) and ventilated
      sweat capsule measurements (dorsal fingers, dorsal hand, forehead, forearm).
      Passive heating significantly elevated auditory canal (0.5 degrees C) and mean
      body temperatures (0.9 degrees C). At each site, the precursor sudomotor
      thresholds occurred at a lower mean body temperature (P < .05), with an average
      elevation of 0.35 degrees C (SD 0.04). However, discharged thresholds were
      delayed until this temperature had risen 0.53 degrees C (SD 0.04), producing
      significant phase delays across sites (mean: 4.1 min [SD 0.5]; P < .05). It is
      concluded that precise sudomotor threshold determinations require methods that
      respond to sweat accumulating within the secretory coil, and not discharged
      secretions, reinforcing the importance of electrodermal techniques.

PMID- 25048253
TI  - Cardiovascular risk factors contribute to disparities in graft outcomes in
      African American renal transplant recipients: a retrospective analysis.
AB  - Data examining cardiovascular (CV) risk factors in renal transplant recipients
      (RTRs) and their contribution to the disparity in graft survival between African
      American (AA) patients and non-AAs is limited. A single-center, retrospective
      analysis of 1003 adult RTRs from January 1, 2000 to May 1, 2008 to inspect the
      impact of race on post-transplant CV events, treatment of CV risk factors and
      their independent influence on graft outcomes was performed. AAs experienced a
      higher incidence of late graft loss, with 1- and 5-year graft survival rates of
      93% and 76% vs 95% and 84% in the non-AA group, respectively. AA patients had a
      higher prevalence of hypertension (HTN) and diabetes mellitus (DM) and
      demonstrated reduced control of DM post-transplant (AA 74% vs non-AA 82%, p =
      0.053). Multivariate analysis for graft survival indicated acute rejection,
      delayed graft function (DGF) and incidence of CV events were significant risk
      factors for graft failure, while the use of beta-blockers, angiotensin-converting
      enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) and 3-hydroxy
      3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors were protective. In
      conclusion, after controlling for CV risk factors and events, race did not have
      an independent effect on outcomes, suggesting CV risk factors and events
      contribute to this disparity. Clinical summary. AAs experienced a higher rate of
      graft failure and CV events; after adjusting for multiple immunological and CV
      risk factors, race no longer remained an independent risk factor for post
      transplant CV events or graft failure; although disparities in post-transplant
      outcomes remain, race alone does not account for the disparity; the racial
      disparity is due to the higher incidence of DGF and acute rejection, as well as
      traditional CV risk factors, including HTN and DM.

PMID- 25048254
TI  - Androgen receptor splice variants in the era of enzalutamide and abiraterone.
AB  - The FDA approvals of enzalutamide and abiraterone have rapidly changed the
      clinical landscape of prostate cancer treatment. Both drugs were designed to
      further suppress androgen receptor (AR) signaling, which is restored following
      first-line androgen deprivation therapies. Resistance to enzalutamide and
      abiraterone, however, is again marked by a return of AR signaling, indicating a
      remarkable "addiction" of prostate cancer cells to the AR pathway. Several
      mechanisms of castration resistance have been uncovered in the past decades,
      featuring a wide spectrum of molecular alterations that may explain sustained AR
      signaling in castration-resistant prostate cancers (CRPC). Among these, the
      androgen receptor splice variants (AR-Vs), particularly variant 7 (AR-V7), have
      been implicated in resistance to enzalutamide and abiraterone in preclinical
      studies, and they cannot be targeted by currently available AR-directed drugs.
      Drug development for AR-V-associated CRPC may therefore be necessary to augment
      the preexisting treatment repertoire. In this mini-review, we will discuss
      general mechanisms of resistance to AR-directed therapies, with a focus on the
      role of androgen receptor splice variants in the new era of treating advanced
      prostate cancer with enzalutamide and abiraterone. 

PMID- 25048255
TI  - The association of reproductive and lifestyle factors with a score of multiple
      endogenous hormones.
AB  - INTRODUCTION: We recently reported that high levels of multiple sex and growth
      hormones were associated with increased postmenopausal breast cancer risk.
      Limited research has explored the relationship between reproductive,
      anthropometric, and lifestyle factors and levels of multiple hormones
      simultaneously. METHODS: This cross-sectional analysis included 738
      postmenopausal Nurses' Health Study participants who were controls in a breast
      cancer nested case-control study and had measured levels of estrone, estradiol,
      estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate,
      prolactin, and sex hormone binding globulin (SHBG). A score was created by
      summing the number of hormones a woman had above (below for SHBG) each hormone's
      age-adjusted geometric mean. The association between lifestyle, anthropometric,
      and reproductive exposures and the score was assessed using generalized linear
      models. RESULTS: The hormone score ranged from 0 to 8 with a mean of 4.0
      (standard deviation = 2.2). Body mass index (BMI) and alcohol consumption at
      blood draw were positively associated with the hormone score: a 5 unit increase
      in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score
      (p < 0.0001) and each 15 g/day increase in alcohol consumption was associated
      with a 0.41 (95%CI: 0.18, 0.63) unit increase in the score (p = 0.0004). Family
      history of breast cancer, age at menarche, and physical activity were not
      associated with the score. CONCLUSIONS: Reproductive breast cancer risk factors
      were not associated with elevated levels of multiple endogenous hormones, whereas
      anthropometric and lifestyle factors, particularly BMI and alcohol consumption,
      tended to be associated with higher levels of multiple hormones.

PMID- 25048256
TI  - [Gastric carcinoid tumor as an infrequent cause of ferropenic anemia].

PMID- 25048257
TI  - Minimally invasive surgery of distal radius fractures: a series of 20 cases using
      a 15mm anterior approach and arthroscopy.
AB  - This study reports the results of minimally invasive surgical treatment of distal
      radius fractures using a 15mm incision with arthroscopic assistance. This was a
      retrospective series of 20 distal radius fractures in young or middle-aged
      patients caused by high-energy trauma and/or with articular involvement. The
      surgical procedure included two stages: fixation using a locking plate and then
      arthroscopy. The incision for plating was always 15mm long. Arthroscopy was used
      to reduce osteochondral fragments in two cases and to suture and pin six
      scapholunate lesions. After a mean follow-up of 4.3 months, the mean pain score
      was 1.9, QuickDASH was 24.6 and the mobility and grip strength were at least 75%
      of the contralateral side. The mean palmar tilt was 8.8 degrees  and the mean
      radial inclination 20.7 degrees . The radio-ulnar index was -1mm with no DISI and
      the scapholunate gap was 1.5mm. There were three cases of CRPS type I. Our
      results show that arthroscopy-assisted, minimally invasive surgery for distal
      radius fractures using a 15mm incision results in a scar with good cosmetics and
      allows for easy reduction and fixation, and management of articular and ligament
      lesions. Its indications must take into account the functional demands placed on
      the wrist by the patient, energy of the trauma and fracture type. LEVEL OF
      EVIDENCE: IV.

PMID- 25048258
TI  - Decellularized human Schneiderian membrane: electron microscopic study as a
      bioscaffold and preliminary cell seeding.
AB  - BACKGROUND: Perforation of maxillary sinus mucous membrane is one of the most
      prevalent complications during open sinus lift surgery. Moreover, such
      complication can usually be managed by an absorbable membrane. As far as
      absorbable membranes are concerned, decellularized maxillary sinus mucous
      membrane, which is an extracellular matrix, can be used as a biologic scaffold
      and an insulating membrane in sinus lifting surgery. MATERIALS AND METHODS: The
      decellularization process of the maxillary sinus membrane was performed by means
      of physical and chemical procedures (liquid nitrogen and sodium dodecyl sulfate).
      Then this membrane was used as a bioscaffold for culturing with adult mesenchymal
      stem cells, which were derived from adipose tissue. RESULTS: Histologic
      evaluation of the decellularized scaffold revealed that cells of the Schneiderian
      membrane were compatibly removed via SDS 1%. Moreover, the scan with electron
      microscope (S6N - Leo vp1450, Germany) of the scaffold indicated that the
      collagen fibers of the decellularized maxillary sinus membrane were intact.
      Furthermore, the culture studies carried out showed that this scaffold supported
      cell seeding. CONCLUSION: The decellularized human maxillary Schneiderian
      membrane has a 3D structure similar to that of the extracellular matrix of human
      normal tissues. As a matter of fact, it can be used as a bioscaffold to support
      cell seeding.

PMID- 25048259
TI  - Competitive inhibition reaction mechanisms for the two-step model of protein
      aggregation.
AB  - We propose three new reaction mechanisms for competitive inhibition of protein
      aggregation for the two-step model of protein aggregation. The first mechanism is
      characterized by the inhibition of native protein, the second is characterized by
      the inhibition of aggregation-prone protein and the third mechanism is
      characterized by the mixed inhibition of native and aggregation-prone proteins.
      Rate equations are derived for these mechanisms, and a method is described for
      plotting kinetic results to distinguish these three types of inhibitors. The
      derived rate equations provide a simple way of estimating the inhibition constant
      of native or aggregation-prone protein inhibitors in protein aggregation. The new
      approach is used to estimate the inhibition constants of different peptide
      inhibitors of insulin aggregation. 

PMID- 25048260
TI  - Total synthesis of a eukaryotic chromosome: Redesigning and SCRaMbLE-ing yeast.
AB  - A team of US researchers recently reported the design, assembly and in vivo
      functionality of a synthetic chromosome III (SynIII) for the yeast Saccharomyces
      cerevisiae. The synthetic chromosome was assembled bottom-up from DNA oligomers
      by teams of students working over several years with researchers as the first
      part of an international synthetic yeast genome project. Embedded into the
      sequence of the synthetic chromosome are multiple design changes that include a
      novel in-built recombination scheme that can be induced to catalyse intra
      chromosomal rearrangements in a variety of different conditions. This system,
      along with the other synthetic sequence changes, is intended to aid researchers
      develop a deeper understanding of how genomes function and find new ways to
      exploit yeast in future biotechnologies. The landmark of the first synthesised
      designer eukaryote chromosome, and the power of its massively parallel
      recombination system, provide new perspectives on the future of synthetic biology
      and genome research.

PMID- 25048261
TI  - Tupaia belangeri as an experimental animal model for viral infection.
AB  - Tupaias, or tree shrews, are small mammals that are similar in appearance to
      squirrels. The morphological and behavioral characteristics of the group have
      been extensively characterized, and despite previously being classified as
      primates, recent studies have placed the group in its own family, the Tupaiidae.
      Genomic analysis has revealed that the genus Tupaia is closer to humans than it
      is to rodents. In addition, tupaias are susceptible to hepatitis B virus and
      hepatitis C virus. The only other experimental animal that has been demonstrated
      to be sensitive to both of these viruses is the chimpanzee, but restrictions on
      animal testing have meant that experiments using chimpanzees have become almost
      impossible. Consequently, the development of the tupaia for use as an animal
      infection model could become a powerful tool for hepatitis virus research and in
      preclinical studies on drug development. 

PMID- 25048262
TI  - Distribution, molecular structure and functional analysis of carnitine
      transporter (SLC22A5) in canine lens epithelial cells.
AB  - While carnitine has been reported to have an anti-oxidative role on the ocular
      surface, there has been no report on the existence of a carnitine transporter
      (SLC22A5) in the lens. Therefore, we investigated the carnitine transport
      activity of canine lens epithelial cells (LEC) and determined the molecular
      structure of canine SLC22A5. The carnitine transport activity was 7.16 +/- 0.48
      pmol/mg protein/30 min. Butyrobetaine, the analogue of carnitine, reduced 30% of
      the activity at 50 uM. A coding sequence of canine carnitine transporter was 1694
      bp long and was predicted to encode 557 amino acid polypeptides. The deduced
      amino acid sequence of canine carnitine transporter showed >80% similarity to
      that of mouse and human. Western blot analysis detected the band at 60 kDa in the
      membrane of lens epithelial cells. The high content of carnitine in the lens is
      possibly transported from aqueous humor by SLC22A5.

PMID- 25048263
TI  - Exogenous leptin administered intramuscularly induces sex hormone disorder and Ca
      loss via downregulation of Gnrh and PI3K expression.
AB  - Obesity is a public health problem that increases the risk of metabolic disease,
      infertility, and other chronic health problems. The present study aimed to
      develop a new rat model for sex hormone disorder with overweight and Ca loss by
      intramuscular injection of exogenous leptin (LEP). Thirty female Sprague-Dawley
      (SD) rats (40 days old) were injected thrice intramuscularly with LEP or keyhole
      limpet hemocyanin immunogen. The following analyses were performed to determine
      the development of appetite, overweight, reproductive related-hormones, and
      calcium (Ca)/phosphorus (Pi) in SD rats: measurement of Lee's index, body weight,
      food intake; serum Ca, Pi, and hormone tests by enzyme-linked immunosorbent
      analysis; histological analysis of abdominal fat; real-time polymerase chain
      reaction analysis of neuropeptide Y, pro-opiomelanocortin, gonadotropin-releasing
      hormone (Gnrh) mRNA, and gonadotropin-releasing hormone receptor (Gnrhr) mRNA
      expression; and western blotting analysis of enzyme phosphatidylinositol-3-kinase
      (PI3K). Rats injected with LEP immunogen displayed significantly increased body
      weight, food intake, Lee's index, serum LEP, serum cortisol, fat deposition in
      the abdomen, and decreased hormones including follicle stimulating hormone,
      luteinizing hormone, estradiol, cholecystokinin, and Ca. Exogenous LEP
      administered intramuscularly also downregulate Gnrh and PI3K. In conclusion,
      exogenous LEP administered intramuscularly is a novel animal model for sex
      hormones disorder with overweight and Ca loss in SD rats. The downregulation of
      PI3K and Gnrh may be involved in the development of this animal model. 

PMID- 25048264
TI  - Long-term follow-up study on the engraftment of human hematopoietic stem cells in
      sheep.
AB  - Xenograft models of human hematopoiesis are essential to the study of the
      engraftment and proliferative potential of human hematopoietic stem cells (HSCs)
      in vivo. Immunodeficient mice and fetal sheep are often used as xenogeneic
      recipients because they are immunologically naive. In this study, we transplanted
      human HSCs into fetal sheep and assessed the long-term engraftment of
      transplanted human HSCs after birth. Fourteen sheep were used in this study. In 4
      fetal sheep, HSCs were transduced with homeo-box B4 (HOXB4) gene before
      transplantation, which promoted the expansion of HSCs. Another 4 fetal sheep were
      subjected to non-myeloablative conditioning with busulfan. Seven of these 8 sheep
      showed successful engraftment of human HSCs (1-3% of colony-forming units) as
      assessed after the birth of fetal sheep (5 months post-transplantation), although
      HOXB4-transduced HSCs showed sustained engraftment for up to 40 months. Intact
      HSCs were transplanted into six non-conditioned fetal sheep, and human colony
      forming units were not detected in the sheep after birth. These results suggest
      that, as compared with mouse models, where the short lifespan of mice limits long
      term follow-up of HSC engraftment, the fetal sheep model provides a unique
      perspective for evaluating long-term engraftment and proliferation of human HSCs.

PMID- 25048265
TI  - Administration of an antioxidant prevents lymphoma development in
      transmitochondrial mice overproducing reactive oxygen species.
AB  - Because of the difficulty to exclude possible involvement of nuclear DNA
      mutations, it has been a controversial issue whether pathogenic mutations in
      mitochondrial DNA (mtDNA) and the resultant respiration defects are involved in
      tumor development. To address this issue, our previous study generated
      transmitochondrial mice (mito-mice-ND6(13997)), which possess the nuclear and
      mtDNA backgrounds derived from C57BL/6J (B6) strain mice except that they carry
      B6 mtDNA with a G13997A mutation in the mt-Nd6 gene. Because aged mito-mice
      ND6(13997) simultaneously showed overproduction of reactive oxygen species (ROS)
      in bone marrow cells and high frequency of lymphoma development, current study
      examined the effects of administrating a ROS scavenger on the frequency of
      lymphoma development. We used N-acetylcysteine (NAC) as a ROS scavenger, and
      showed that NAC administration prevented lymphoma development. Moreover, its
      administration induced longevity in mito-mice-ND6(13997). The gene expression
      profiles in bone marrow cells indicated the upregulation of the Fasl gene, which
      can be suppressed by NAC administration. Given that natural-killer (NK) cells
      mediate the apoptosis of various tumor cells via enhanced expression of genes
      encoding apoptotic ligands including Fasl gene, its overexpression would reflect
      the frequent lymphoma development in bone marrow cells. These observations
      suggest that continuous administration of an antioxidant would be an effective
      therapeutics to prevent lymphoma development enhanced by ROS overproduction. 

PMID- 25048266
TI  - Application of 3.0 tesla magnetic resonance imaging for diagnosis in the
      orthotopic nude mouse model of pancreatic cancer.
AB  - The aim of this study was to successfully establish an orthotopic murine model
      using two different human pancreatic adenocarcinoma cell lines and to propose a
      3.0 tesla MRI protocol for noninvasive characterization of this model. SW1990 and
      MIAPaca-2 tumor cells were injected into the pancreas of BALB/C nu/nu mice. Tumor
      growth rate and morphological information were assessed by 3.0 tesla MRI (T1WI,
      T2WI and DCE-MRI) and immunohistology. Proliferation of SW1990 was significantly
      faster than that of MIAPaca-2 (P=0.000), but MIAPaca-2 mice had a significantly
      shorter survival than SW1990 mice (41 days and 44 days respectively, P=0.027).
      MRI could reliably monitor tumor growth in both cell lines: the tumors exhibiting
      a spherical growth pattern showed a high-intensity signal, and the SW1990 group
      developed significantly larger tumors compared with the MIAPaCa-2 group. There
      were no statistical differences between the two groups in which tumor size was
      assessed using electronic calipers and an MRI scan (P=0.680). Both tumors showed
      a slow gradual enhancement pattern. Immunohistochemistry demonstrated tumor
      tissues showing high expression of Ki-67. This model closely mimics human
      pancreatic cancer and permits monitoring of tumor growth and morphological
      information by noninvasive 3.0 tesla MRI studies reducing the number of mice
      required. 

PMID- 25048268
TI  - Effect of mouse strain in a model of chemical-induced respiratory allergy.
AB  - The inhalation of many types of chemicals is a leading cause of allergic
      respiratory diseases, and effective protocols are needed for the detection of
      environmental chemical-related respiratory allergies. In our previous studies, we
      developed a method for detecting environmental chemical-related respiratory
      allergens by using a long-term sensitization-challenge protocol involving BALB/c
      mice. In the current study, we sought to improve our model by characterizing
      strain-associated differences in respiratory allergic reactions to the well-known
      chemical respiratory allergen glutaraldehyde (GA). According to our protocol,
      BALB/c, NC/Nga, C3H/HeN, C57BL/6N, and CBA/J mice were sensitized dermally with
      GA for 3 weeks and then challenged with intratracheal or inhaled GA at 2 weeks
      after the last sensitization. The day after the final challenge, all mice were
      euthanized, and total serum IgE levels were assayed. In addition, immunocyte
      counts, cytokine production, and chemokine levels in the hilar lymph nodes (LNs)
      and bronchoalveolar lavage fluids (BALF) were also assessed. In conclusion,
      BALB/c and NC/Nga mice demonstrated markedly increased IgE reactions.
      Inflammatory cell counts in BALF were increased in the treated groups of all
      strains, especially BALB/c, NC/Nga, and CBA/J strains. Cytokine levels in LNs
      were increased in all treated groups except for C3H/HeN and were particularly
      high in BALB/c and NC/Nga mice. According to our results, we suggest that BALB/c
      and NC/Nga are highly susceptible to respiratory allergic responses and therefore
      are good candidates for use in our model for detecting environmental chemical
      respiratory allergens. 

PMID- 25048269
TI  - On function, cause, and being Jerry Hogan's student.
AB  - Jerry Hogan has forcefully maintained that cause and function are distinct
      questions, and that attempts to integrate them are conceptually muddled. I
      dissent from his view, maintaining that causal analysis is conducted in the
      shadow of premises about function, and that bringing functional ideas out of the
      shadows facilitates the generation of fruitful causal hypotheses. This is not to
      suggest, however, that cause-function muddles are non-existent; I agree with
      Hogan that they are both common and mischievous. This article is part of a
      Special Issue entitled: In Honor of Jerry Hogan.

PMID- 25048267
TI  - Gut microbial diversity in rat model induced by rhubarb.
AB  - Rhubarb is often used to establish chronic diarrhea and spleen (Pi)-deficiency
      syndrome animal models in China. In this study, we utilized the enterobacterial
      repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) method to
      detect changes in bacterial diversity in feces and the bowel mucosa associated
      with this model. Total microbial genomic DNA from the small bowel (duodenum,
      jejunum, and ileum), large bowel (proximal colon, distal colon, and rectum),
      cecum, and feces of normal and rhubarb-exposed rats were used as templates for
      the ERIC-PCR analysis. We found that the fecal microbial composition did not
      correspond to the bowel bacteria mix. More bacterial diversity was observed in
      the ileum of rhubarb-exposed rats (P<0.05). Furthermore, a 380 bp product was
      found to be increased in rhubarb-exposed rats both in faces and the bowel mucosa.
      The product was cloned and sequenced and showed high similarity with regions of
      the Bacteroides genome. AS a result of discriminant analysis with the SPSS
      software, the Canonical Discriminant Function Formulae for model rats was
      established. 

PMID- 25048270
TI  - Palladium nanoparticles bonded to two-dimensional iron oxide graphene nanosheets:
      a synergistic and highly reusable catalyst for the Tsuji-Trost reaction in water
      and air.
AB  - Low cost, high activity and selectivity, convenient separation, and increased
      reusability are the main requirements for noble-metal-nanocatalyst-catalyzed
      reactions. Despite tremendous efforts, developing noble-metal nanocatalysts to
      meet the above requirements remains a significant challenge. Here we present a
      general strategy for the preparation of strongly coupled Fe(3)O(4) and palladium
      nanoparticles (PdNPs) to graphene sheets by employing polyethyleneimine as the
      coupling linker. Transmission electron microscopic images show that Pd and
      Fe(3)O(4) nanoparticles are highly dispersed on the graphene surface, and the
      mean particle size of Pd is around 3 nm. This nanocatalyst exhibits synergistic
      catalysis by Pd nanoparticles supported on reduced graphene oxide (rGO) and a
      tertiary amine of polyethyleneimine (Pd/Fe(3)O(4)/PEI/rGO) for the Tsuji-Trost
      reaction in water and air. For example, the reaction of ethyl acetoacetate with
      allyl ethyl carbonate afforded the allylated product in more than 99 % isolated
      yield, and the turnover frequency reached 2200 h(-1). The yield of allylated
      products was 66 % for Pd/rGO without polyethyleneimine. The catalyst could be
      readily recycled by a magnet and reused more than 30 times without appreciable
      loss of activity. In addition, only about 7.5 % of Pd species leached off after
      20 cycles, thus rendering this catalyst safer for the environment.

PMID- 25048271
TI  - Influence of lifestyle modifications on age-related free radical injury to brain.
AB  - IMPORTANCE: The Healthy Brain Initiative 2013-2018 seeks to optimize brain health
      as we age. Free radical injury is an important effector of molecular and cellular
      stress in the aging brain that derives from multiple sources. OBJECTIVE: To
      identify potentially modifiable risk factors associated with increased markers of
      brain oxidative stress. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional,
      academic multicenter study consisted of 320 research volunteers (172 women) aged
      21 to 100 years who were medically healthy and cognitively normal. MAIN OUTCOMES
      AND MEASURES: Free radical injury to the brain was assessed using cerebrospinal
      fluid (CSF) F2-isoprostane (F2-IsoP) concentrations correlated with age, sex,
      race, cigarette smoking, body mass index, inheritance of the epsilon4 allele of
      the apolipoprotein E gene (APOE), and CSF biomarkers of Alzheimer disease.
      RESULTS: The concentration of CSF F2-IsoP increased with age by approximately 3
      pg/mL (approximately 10%) from age 45 to 71 years in medically healthy,
      cognitively normal adults (P < .001). The CSF F2-IsoP concentration increased by
      approximately more than 10% for every 5-U increase in body mass index (P < .001).
      Current smoking had an approximately 3-fold greater effect on CSF F2-IsoPs
      compared with age (P < .001). Women had greater mean CSF F2-IsoP concentrations
      than men at all ages after adjusting for other factors (P = .02). Neither the
      concentration of CSF Alzheimer disease biomarkers nor inheritance of the APOE
      epsilon4 allele was associated with the CSF F2-IsoP concentration in this group
      of medically healthy, cognitively normal adults (P > .05). The association
      between CSF F2-IsoP concentrations and race was not significant after controlling
      for the effect of current smoking status (P = .45). CONCLUSIONS AND RELEVANCE:
      Our results are consistent with an age-related increase in free radical injury in
      the human brain and uniquely suggest that this form of injury may be greater in
      women than in men. Our results also highlighted 2 lifestyle modifications (ie,
      body mass index and smoking) that would have an even greater effect on
      suppressing free radical injury to the brain than would suppressing the processes
      of aging. These results inform efforts to achieve success in the Healthy Brain
      Initiative 2013-2018.

PMID- 25048272
TI  - [Structured neuromuscular warm-up for injury prevention in young elite football
      players].
AB  - OBJECTIVE: To gather evidence about the outcomes of structured neuromuscular warm
      up programs without additional equipment, as prevention of non-contact injuries
      in young professional soccer players. MATERIAL AND METHODS: A literature search
      was conducted during March and April 2013 (PubMed, Cochrane Library, The American
      Journal of Sports Medicine, The British Journal of Sports Medicine and the search
      engine Trip Database). RESULTS: After applying the inclusion and exclusion
      criteria, a total of 6 studies were obtained (3 clinical trials, one cohort study
      and 2 systematic reviews). "FIFA 11+" program showed a reduction of injuries of
      between 33% and 57%. These included 52% in knee, 22% in ankle, 40% in medial
      tibial stress syndrome, 50% in posterior thigh, and 21% in the anterior, and 12%
      in the groin area. "FIFA 11" program showed a 58% reduction in ankle sprains and
      27% in anterior cruciate ligament (ACL) injuries. Other specific programs to
      prevent ACL injuries reduced them by 74% and "Knakontroll, SISU Idrottsbocker(c)"
      by 64%. "HarmoKnee" program reduced knee injuries by 78%. DISCUSSION: Several
      methodological weaknesses were observed, but it seems that there is a trend
      toward a warm-up that contains basic stretching, strengthening and balance
      exercises, which performed for more than three months and regularly, could
      prevent injuries. CONCLUSIONS: "FIFA 11 +" program might be a good preventive
      measure of injuries by implementing its program of structured warm- up. In any
      event new, better designed, studies are needed to assess this evidence.

PMID- 25048273
TI  - [Risk factors for total hip arthroplasty dislocation and its functional
      outcomes].
AB  - OBJECTIVES: To evaluate risk factors for dislocation after primary total hip
      arthroplasty (THA), and its functional outcomes. MATERIAL AND METHODS: A
      retrospective study was conducted on 22 cases with dislocation and 431 controls
      without dislocation, all performed with lateral access. The data were collected
      prospectively with a minimum follow-up of 5 years. Patient related factors, from
      primary surgery, and position of components on simple radiographs were analyzed.
      Harris and Merle D'Aubigne hip scores, and short Womac questionnaire were used.
      RESULTS: Demographic, patient-related or surgical technique factors were not risk
      predictors of dislocation. With regard to position of components, an acetabular
      abduction >50 degrees  (p = 0.003) and anteversion lower or higher than 10
      degrees - 20 degrees  (p = 0.044) were risk factors. Controls and dislocation
      treated conservatively had similar outcomes, and in both were better than in
      those treated with surgical revision (p = 0.03). DISCUSSION: Factors relating to
      the patient and soft tissues status may influence the stability of the
      arthroplasty, but malposition of the acetabular component seems to be the most
      important and common risk factor for dislocation.

PMID- 25048274
TI  - [Corticosteroid therapy for acute spinal cord injury: the NASCIS controversy].

PMID- 25048275
TI  - [Surgical treatment of distal biceps tendon ruptures with bone anchors using a
      single anterior approach].
AB  - PURPOSE: To evaluate the clinical results of reinsertion of the distal biceps
      tendon with anterior bone anchors. MATERIAL AND METHODS: A retrospective study
      was conducted on 79 patients who underwent reinsertion of the distal biceps
      tendon with anterior bone anchors. The mean age was 46 years (range, 32-64). Two
      anchors were used in 57% of cases, and one anchor in 43%. The same postoperative
      protocol was performed in all patients. Functional assessment was made using a
      Motor evoked potentials (MEPS) functional scale. The mean of follow-up time was
      20 months (range, 12 -28 months). RESULTS: The final mean of MEPS score was 95.2
      points (SD 6.8). Almost all (94%) patients had excellent and good results, and 6%
      a bad result. No differences were observed when comparing functional outcome
      among patients in whom one anchor was used (96 points) with those in whom two
      anchors were used (95 points), p=0.5. The mean time off work was 14 weeks (range,
      5-56) and 100% of patients were able to return to work. The incidence of
      complications was 13%. The most frequent was neuropraxia of the lateral
      antebrachial cutaneous nerve. CONCLUSION: The anatomic re-attachment of the
      distal biceps tendon with bone anchors using a single anterior approach is a safe
      technique that offers excellent and good functional results in the medium term.

PMID- 25048276
TI  - Controlling the assembly of CdS nanorods via solvent and acidity.
AB  - We report control over the phase behavior of CdS nanorods via the solvent and
      acidity. CdS nanorods were synthesized using alkane phosphonic acid ligands,
      which were replaced after synthesis by a series of aromatic ligands. Change of
      ligand enabled us to cast films from different solvents. By replacing toluene
      with ethanol or water the rod-rod interactions dominate over rod-substrate
      interactions, thereby favoring simple hexagonal ordering (2D). When dispersed in
      water, a net electrostatic charge on the nanorods could be induced by
      deprotonating the ligands at high pH. This net charge favors 2D nematic ordering
      over homeotropic ordering of the nanorods on a substrate. A calculation of the
      van der Waals and electrostatic interactions is presented that explains the
      observed influence of solvent and pH. 

PMID- 25048277
TI  - Electrochemical discrimination between G-quadruplex and duplex DNA.
AB  - Analytical tools enabling the discrimination between duplex DNA and G-quadruplex
      DNA are necessary to unravel the biological function(s) of G-quadruplexes. A
      methodology relying on the electrochemical response of the electroactive
      hexaammineruthenium(III) cation at DNA-modified surfaces is presented. A
      characteristic voltammetric peak is evidenced for all the investigated G
      quadruplex sequences, encompassing various types of folding and numbers of
      quartets. In contrast, no such peak is detected for dsDNA sequences. The
      occurrence of the voltammetric peak is the consequence of a strong association
      between the hexaammineruthenium ligand and the surface-immobilized G
      quadruplexes. The peak potential points to a significant contribution of
      nonelectrostatic interactions between the electroactive ligand and G
      quadruplexes. The very good efficiency of the discrimination methodology is
      demonstrated by comparing a G-quadruplex and its corresponding duplex. 

PMID- 25048278
TI  - Is the all-arthroscopic tibial inlay double-bundle PCL reconstruction a viable
      option in multiligament knee injuries?
AB  - BACKGROUND: All-arthroscopic tibial inlay double-bundle (DB) posterior cruciate
      ligament (PCL) reconstruction avoids an open dissection and the "killer turn"
      while maintaining the advantage of an anatomic graft. However, clinical data on
      the viability of this surgical technique in multiligamentous knee injuries are
      lacking. QUESTIONS/PURPOSES: At greater than 2 years of followup, we evaluated
      (1) validated outcomes scores; (2) range of motion; and (3) side-to-side
      stability on PCL stress radiographs of a small group of patients who underwent
      all-arthroscopic tibial inlay DB PCL reconstruction in multiligamentous knee
      injuries, either shortly after injury or late. METHODS: All patients sustaining
      an operative multiligamentous knee injury between August 2007 and March 2009
      underwent PCL reconstruction with the all-arthroscopic tibial inlay DB PCL
      reconstruction. Twelve patients sustained such injuries and were reconstructed
      during the study period and all 12 returned for followup with a minimum of 2
      years (mean 3 +/- 0.8 years). There were nine males and three females, with a
      mean age of 30 years; four patients had a subacute reconstruction (>= 3 weeks,
      but < 3 months), and eight patients had chronic reconstructions (> 3 months).
      Mean time from injury to PCL reconstruction was 7 +/- 12 months. Demographics,
      ROM, outcome scores (Lysholm and International Knee Documentation Committee
      [IKDC] scores), and PCL stress views were obtained. RESULTS: At final followup,
      mean Lysholm and IKDC subjective scores were 79 +/- 16 and 72 +/- 19,
      respectively. IKDC objective scores included eight nearly normal knees, three
      abnormal knees, and one severely abnormal knee. Mean flexion and extension losses
      compared with the contralateral were 10 +/- 9 and 1 +/- 2, respectively. Mean +/-
      SD final side-to-side difference on PCL stress radiographs was 5 +/- 3 mm.
      CONCLUSIONS: The clinical and radiographic results of the all-arthroscopic tibial
      inlay DB PCL reconstruction appear comparable to the same technique in isolated
      PCL injuries and, based on similar published case series, comparable to results
      of multiligamentous knee reconstructions using other PCL reconstruction
      techniques. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions
      for Authors for a complete description of levels of evidence.

PMID- 25048279
TI  - Patient-specific anatomical and functional parameters provide new insights into
      the pathomechanism of cam FAI.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) represents a constellation of
      anatomical and clinical features, but definitive diagnosis is often difficult.
      The high prevalence of cam deformity of the femoral head in the asymptomatic
      population as well as clinical factors leading to the onset of symptoms raises
      questions as to what other factors increase the risk of cartilage damage and hip
      pain. QUESTIONS/PURPOSES: The purpose was to identify any differences in
      anatomical parameters and squat kinematics among symptomatic, asymptomatic, and
      control individuals and if these parameters can determine individuals at risk of
      developing symptoms of cam FAI. METHODS: Forty-three participants (n = 43) were
      recruited and divided into three groups: symptomatic (12), asymptomatic (17), and
      control (14). Symptomatic participants presented a cam deformity (identified by
      an elevated alpha angle on CT images), pain symptoms, clinical signs, and were
      scheduled for surgery. The other recruited volunteers were blinded and unaware
      whether they had a cam deformity. After the CT data were assessed for an elevated
      alpha angle, participants with a cam deformity but who did not demonstrate any
      clinical signs or symptoms were considered asymptomatic, whereas participants
      without a cam deformity and without clinical signs or symptoms were considered
      healthy control subjects. For each participant, anatomical CT parameters (axial
      alpha angle, radial alpha angle, femoral head-neck offset, femoral neck-shaft
      angle, medial proximal femoral angle, femoral torsion, acetabular version) were
      evaluated. Functional squat parameters (maximal squat depth, pelvic range of
      motion) were determined using a motion capture system. A stepwise discriminant
      function analysis was used to determine which of the parameters were most
      suitable to classify each participant with their respective subgroup. RESULTS:
      The symptomatic group showed elevated alpha angles and lower femoral neck-shaft
      angles, whereas the asymptomatic group showed elevated alpha angles in comparison
      with the control group. The best discriminating parameters to determine symptoms
      were radial alpha angle, femoral neck-shaft angle, and pelvic range of motion (p
      < 0.001). CONCLUSIONS: In the presence of a cam deformity, indications of a
      decreased femoral neck-shaft angle and reduced pelvic range of motion can
      identify those at risk of symptomatic FAI.

PMID- 25048280
TI  - CORR(r) curriculum--osteopathic and allopathic residency education: Why not the
      same standards?

PMID- 25048281
TI  - Editorial comment: Symposium: management of the dislocated knee.

PMID- 25048282
TI  - Is curettage and high-speed burring sufficient treatment for aneurysmal bone
      cysts?
AB  - BACKGROUND: To decrease the recurrence rate after intralesional curettage for
      aneurysmal bone cysts, different adjuvant treatments have been recommended.
      Liquid nitrogen spray and argon beam coagulation have provided the lowest
      recurrence rates, but unlike the high-speed burr, these adjuvants are not always
      available in operating rooms. QUESTIONS/PURPOSES: We asked: (1) Is high-speed
      burring alone sufficient as an adjuvant to curettage with respect to recurrence
      rates? (2) What is the complication rate from this technique? (3) What are the
      risk factors for local recurrence? METHODS: A retrospective review of the
      database of the University Musculoskeletal Tumor Unit and the private files of
      the senior author (EHW) for a period of 19 years (1993-2011) was performed to
      identify all patients histologically diagnosed with primary aneurysmal bone cyst.
      During that period, patients with aneurysmal bone cysts were treated with
      intralesional curettage, burring, and bone grafting if the lesions showed an
      adequate cortical wall or a wall with thinned out portions which could be
      reconstructed with bone grafting. Based on those indications, we treated 54
      patients for this condition. Of those, 18 were treated using approaches other
      than burring because they did not meet the defined indications, and an additional
      five patients were lost to followup before 2 years, leaving 31 patients for
      analysis, all of whom were followed up for at least 2 years (mean, 7 years;
      range, 2-18 years). RESULTS: Of these 31 patients, one had a recurrence (3.2%).
      Complications using this approach occurred in three patients (9.7%), and included
      growth plate deformity (1) and genu varus (2) secondary to collapse of the
      reconstructed condyle. With only one recurrence, we cannot answer what the risk
      factors might be for recurrence; however, the one patient with recurrence
      presented with a large lesion and a pathologic fracture. CONCLUSIONS: Curettage,
      burring, and bone grafting compare favorably in the literature with other
      approaches for aneurysmal bone cysts, such as cryotherapy and argon-beam
      coagulation. We conclude that high-speed burring alone as an adjuvant to
      intralesional curettage is a reasonable approach to achieving a low recurrence
      rate for aneurysmal bone cysts. LEVEL OF EVIDENCE: Level IV, therapeutic study.
      See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25048283
TI  - Copper(II) complexes with 4-hydroxyacetophenone-derived acylhydrazones:
      synthesis, characterization, DNA binding and cleavage properties.
AB  - Two new Cu(II) complexes of Schiff base-hydrazone ligands, hydroxy-N'-[(1Z)-1-(4
      hydroxyphenyl)ethylidene]benzohydrazide [H3L(1)] and ethyl 2-(4-(1-(2-(4-(2
      ethoxy-2-oxoethoxy)benzoyl)hydrazono)ethyl)phenoxy)acetate (HL(2)) have been
      synthesized and then characterized by microcopy and spectral studies. X-ray
      powder diffraction illustrates that [Cu(L(2))2] complex is crystalline in nature
      whereas [Cu(H2L(1))2].2H2O has an amorphous structure. Binding of the copper
      complexes with Calf thymus DNA (CT-DNA) has been investigated by UV-visible
      spectra, exhibiting non-covalent binding to CT-DNA. DNA cleavage experiments have
      been also investigated by agarose gel electrophoresis in the presence and absence
      of an oxidative agent (H2O2). The effect of complex concentration on the DNA
      cleavage reaction has been also studied. Both copper complexes show nuclease
      activity, which significantly depends on concentrations of the complexes, in the
      presence of H2O2 through oxidative mechanism whereas they slightly cleavage DNA
      in the absence an oxidative agent.

PMID- 25048284
TI  - Vibrational spectroscopic (FTIR and FT-Raman), first-order hyperpolarizablity,
      HOMO, LUMO, NBO, Mulliken charge analyses of 2-ethylimidazole based on Hartree
      Fock and DFT calculations.
AB  - The FTIR and FT-Raman spectra of 2-ethylimidazole (2EIDZ) have been recorded in
      the region 4000-400 cm(-1) and 3500-50 cm(-1), respectively. Utilizing the
      observed FTIR and FT-Raman data, a complete vibrational assignment and analysis
      of the fundamental modes of the compound were carried out. The optimized
      molecular geometry, harmonic vibrational frequencies, infrared intensities and
      Raman scattering activities, were calculated by ab initio Hartree-Fock (HF) and
      density functional theory (DFT/B3LYP) methods with 6-311++G(d,p) basis set. The
      difference between the observed and scaled wavenumber values of most of the
      fundamentals is very small. A detailed interpretation of the infrared and Raman
      spectra of 2EIDZ is also reported based on total energy distribution (TED). The
      values of the total dipole moment (MU) and the first-order hyperpolarizability
      (beta) of the compound were computed. Stability of the molecule arising from
      hyperconjugative interactions, charge delocalization have been analyzed using
      natural bond orbital (NBO) analysis. Besides, HOMO and LUMO analysis, Mulliken's
      charge analysis and several thermodynamic properties have been calculated.

PMID- 25048285
TI  - Experimental and molecular modeling studies of the interaction of the polypyridyl
      Fe(II) and Fe(III) complexes with DNA and BSA.
AB  - Two mononuclear iron complexes, [Fe(tppz)2](PF6)2.H2O (1) and Fe(tppz)Cl3.2CHCl3
      (2) where tppz is (2,3,5,6-tetra(2-pyridyl)pyrazine), have been synthesized and
      characterized by elemental analysis, spectroscopic methods (UV-Vis and IR) and
      single crystal X-ray structure analysis. The interaction of (1) as the nitrate
      salt ([Fe(tppz)2](NO3)2) with calf-thymus DNA (CT-DNA) has been monitored by UV
      Vis spectroscopy, competitive fluorescence titration, circular dichroism (CD),
      voltammetric techniques, viscosity measurement, and gel electrophoresis. Gel
      electrophoresis of DNA with [Fe(tppz)2](NO3)2 demonstrated that the complex also
      has the ability to cleave supercoiled plasmid DNA. The results have indicated
      that the complex binds to CT-DNA by three binding modes, viz., electrostatic,
      groove and partial insertion of the pyridyl rings between the base stacks of
      double-stranded DNA. Molecular docking of [Fe(tppz)2](NO3)2 with the DNA sequence
      d(ACCGACGTCGGT)2 suggests the complex fits into the major groove. The water
      insoluble complex (2) can catalyze the cleavage of BSA at 40  degrees C. There
      are no reports of the catalytic effect of polypyridyl metal complexes on the BSA
      cleavage. Molecular docking of (2) with BSA suggests that, when the chloro
      ligands in the axial positions are replaced by water molecules, the BSA can
      interact with the Fe(III) complex more easily.

PMID- 25048286
TI  - Growth, spectral, anisotropic, second and third order nonlinear optical studies
      on potential nonlinear optical crystal anilinium perchlorate (AP) for NLO device
      fabrications.
AB  - A new semiorganic nonlinear optical material anilinium perchlorate was grown by
      the slow evaporation technique using water as solvent. The solubility and meta
      stable zone width were determined. The anilinium perchlorate crystal belongs to
      orthorhombic system with noncentrosymmetric space group P212121. The presence of
      various functional groups was identified by FT-IR FT-Raman spectrum. The
      morphology of the anilinium perchlorate crystal was studied. From this
      morphology, anilinium perchlorate crystal plate was cut along three prominent
      planes, such as (001), (010) and (20-1). The thermal stability of the crystal was
      determined using TG-DTA studies. The hardness, laser damage threshold,
      transmittance, reflectance, experimental refractive index of the crystal was
      found. The particle size dependent second harmonic generation efficiency for
      anilinium perchlorate was evaluated by Kurtz-Perry powder method using Nd:YAG
      laser, which established the existence of phase matching. The third order
      nonlinear refractive index and nonlinear absorption coefficient of the grown
      crystal were measured by Z-scan studies.

PMID- 25048287
TI  - Infrared spectroscopic study of SO42- ions included in M'2M''(SeO4)2?6H2O (Me'=K,
      NH4+; M''=Mg, Co, Ni, Cu, Zn) and NH4+ ions included in K2M(XO4)2?6H2O (X=S, Se;
      M''=Mg, Co, Ni, Cu, Zn).
AB  - Infrared spectra of Tutton compounds, M'2M''(SeO4)2?6H2O (M'=K, NH4+; M''=Mg, Co,
      Ni, Cu, Zn; X=S, Se), as well as those of SO42- guest ions included in selenate
      host lattices and of NH4(+) guest ions included in potassium host lattices are
      presented and discussed in the regions of nu3 and nu1 of SO42- guest ions, nu4 of
      NH4+ guest ions and water librations. The SO42- guest ions matrix-isolated in
      selenate matrices (approximately 2 mol%) exhibit three bands corresponding to nu3
      and one band corresponding to nu1 in good agreement with the low site symmetry C1
      of the host selenate ions. When the larger SO42- ions are replaced by the smaller
      SO42- ions the mean values of the asymmetric stretching modes nu3 of the included
      SO42- ions are slightly shifted to lower frequencies as compared to those of the
      same ions in the neat sulfate compounds due to the smaller repulsion potential of
      the selenate matrices (larger unit-cell volumes of the selenates). It has been
      established that the extent of energetic distortion of the sulfate ions matrix
      isolated in the ammonium selenates as deduced from the values of Deltanu3 and
      Deltanu3/nuc is stronger than that of the same ions matrix-isolated in the
      potassium selenates due to the formation of hydrogen bonds between the SO42-
      guest ions with both the water molecules in the host compounds and the NH4+ host
      ions (for example, Deltanu3 of the sulfate guest ions have values of 30 and 51
      cm(-1) in the nickel potassium and ammonium compounds, and 33 and 49 cm(-1) in
      the zinc potassium and ammonium compounds, respectively). The infrared spectra of
      ammonium doped potassium sulfate matrices show three bands corresponding to
      Deltanu4 of the included ammonium ions in agreement with the low site symmetry C1
      of the host potassium ions. However, the inclusion of ammonium ions in selenate
      matrices (with exception of the magnesium compound) leads to the appearance of
      four bands in the region of nu4. At that stage of our knowledge we assume that
      some kind of disorder of the ammonium ions included in selenate lattices occurs
      due to the different proton acceptor capability of the SO42- and SO42- ions. The
      latter ions are known to exhibit stronger proton acceptor abilities. This fact
      will facilitate the formation of polyfurcate hydrogen bonds of the ammonium ions
      in the selenate matrices, thus leading to increasing in the coordination number
      of these ions, i.e. to a disorder of the ammonium guest ions. The strength of the
      hydrogen bonds formed in the title Tutton compounds as well as that of the
      hydrogen bonds in potassium compounds containing isomorphously included ammonium
      ions as deduced from the wavenumbers of the water librations are also discussed.
      The bands corresponding to water librations in the spectra of the mixed crystals
      K1.8(NH4)0.2M(XO4)2?6H2O (M=Mg, Co, Ni, Cu, Zn; X=S, Se) broaden and shift to
      lower frequencies as compared to those of the potassium host compounds, thus
      indicating that weaker hydrogen bonds are formed in the mixed crystals. These
      spectroscopic findings are owing to the decrease in the proton acceptor capacity
      of the SO42- and SO42- ions due to the formation of hydrogen bonds between the
      host anions and the guest ammonium cations additionally to water molecules (anti
      cooperative or proton acceptor competitive effect). Furthermore, the band shifts
      in the spectra of the selenate matrices are generally larger than those observed
      in the spectra of the respective sulfates due to the stronger proton acceptor
      ability of the selenate ions.

PMID- 25048288
TI  - Modeling the antisymmetric and symmetric stretching vibrational modes of aqueous
      carboxylate anions.
AB  - The infrared spectra of six aqueous carboxylate anions have been calculated at
      the M05-2X/cc-pVTZ level of theory with the SMD solvent model, and validated
      against experimental data from the literature over the region of 1700 cm(-1) to
      1250 cm(-1); this region corresponds to the stretching modes of the carboxylate
      group, and is often interrogated when probing bonding of carboxylates to other
      species and surfaces. The anions studied here were formate, acetate, oxalate,
      succinate, glutarate and citrate. For the lowest energy conformer of each anion,
      the carboxylate moiety antisymmetric stretching peak was predicted with a mean
      signed error of only 4 cm(-1) using the SMD solvent model, while the symmetric
      peak was slightly overestimated. Performing calculations in vacuum and scaling
      was found to generally over-predict the antisymmetric vibrational frequencies and
      under predict the symmetric peak. Different conformers of the same anion were
      found to have only slightly different spectra in the studied region and the
      inclusion of explicit water molecules was not found to significantly change the
      calculated spectra when the implicit solvent model is used. Overall, the use of
      density functional theory in conjunction with an implicit solvent model was found
      to result in infra-red spectra that are the best reproduction of the features
      found experimentally for the aqueous carboxylate ions in the important 1700 cm(
      1) to 1250 cm(-1) region. The development of validated model chemistries for
      simulating the stretching modes of aqueous carboxylate ions will be valuable for
      future studies that investigate how carboxylate anions complex with multivalent
      metal cations and related species in solution.

PMID- 25048289
TI  - Acute extrapyramidal syndrome induced by escitalopram: a case report.

PMID- 25048290
TI  - Bradykinin induces vascular contraction after hemorrhagic shock in rats.
AB  - BACKGROUND: Bradykinin (BK) has many biological effects in inflammation, allergy,
      and septic shock. Studies have shown that low doses of BK can induce vascular
      relaxation and high doses can induce vascular contraction in many
      pathophysiological conditions, but the role and mechanisms that high doses of BK
      have on vascular contraction in hemorrhagic shock are not clear. METHODS: With
      hemorrhagic-shock rats and hypoxia-treated superior mesenteric artery (SMA), we
      investigated the role and mechanisms of high doses of BK-induced vascular
      contraction in hemorrhagic shock. RESULTS: High doses of BK (500-50,000 ng/kg in
      vivo or 10(-10) to 10(-5) mol/L in vitro) dose dependently induced vascular
      contraction of SMA and increased the vascular calcium sensitivity in normal and
      hemorrhagic-shock rats. Less than 10(-10) mol/L of BK induced vascular dilation
      BK-induced increase of vascular contractile response and calcium sensitivity was
      reduced by denudation of the endothelium, 18alpha-glycyrrhetic acid (an inhibitor
      of myoendothelial gap junction) and connexin 43 antisense oligodeoxynucleotide.
      Further studies found that high concentrations of BK-induced vascular contraction
      in hemorrhagic shock was closely related to the activation of Rho A-Rho kinase
      pathway and Protein Kinase C (PKC) alpha and epsilon. CONCLUSIONS: High doses of
      BK can induce vascular contraction in hemorrhagic shock condition, which is
      endothelium and myoendothelial gap junction dependent. Cx43-mediated activation
      of Rho A-Rho kinase and Protein Kinase C (PKC) pathway plays a very important
      role in this process. This finding provided a new angle of view to the biological
      role of BK in other pathophysiological conditions such as hemorrhagic shock or
      hypoxia.

PMID- 25048291
TI  - Melanocortin-4 receptor (MC4R) polymorphisms are associated with growth and meat
      quality traits in sheep.
AB  - The involvement of melanocortin 4 receptor gene (MC4R) in food intake and body
      weight regulation is well characterized. MC4R mutations are the most frequent
      monogenic cause of human obesity. Significant associations have been revealed
      between MC4R mutations and productive traits in pigs, cattle and poultry. Herein,
      fluorescence-based conformation sensitive gel electrophoresis was used to
      identify two single nucleotide polymorphisms (SNPs) in the coding region (93G>A
      and 292G>A) and two SNPs in the 3'-UTR area (1016G>A and 1240T>C) of MC4R gene in
      132 German Merino sheep. We found that the 1016G>A mutation in the 3'-UTR was
      significantly associated with body weight at 120 and 180 days, average daily
      gain, back fat thickness and loin-eye area. Allele A located at the 292th
      position of MC4R gene representing Arg98 was associated with significantly higher
      loin-eye area in sheep. For the synonymous 93G>A mutation, A allele carrier
      animals had higher back fat thickness. Our results provide evidence that the MC4R
      gene may be a candidate gene for growth and meat quality traits with MC4R SNPs
      being potentially valuable as genetic markers for economic traits in German
      Merino sheep.

PMID- 25048292
TI  - Utility of indels for species-level identification of a biologically complex
      plant group: a study with intergenic spacer in Citrus.
AB  - The Consortium of Barcode of Life plant working group proposed to use the defined
      portion of plastid genes rbcL and matK either singly or in combination as the
      standard DNA barcode for plants. But DNA barcode based identification of
      biologically complex plant groups are always a challenging task due to the
      occurrence of natural hybridization. Here, we examined the use of indels
      polymorphism in trnH-psbA and trnL-trnF sequences for rapid species
      identification of citrus. DNA from young leaves of selected citrus species were
      isolated and matK gene (~800 bp) and trnH-psbA spacer (~450 bp) of Chloroplast
      DNA was amplified for species level identification. The sequences within the
      group taxa of Citrus were aligned using the ClustalX program. With few obvious
      misalignments were corrected manually using the similarity criterion. We
      identified a 54 bp inverted repeat or palindrome sequence (27-80 regions) and 6
      multi residues indel coding regions. Large inverted repeats in cpDNA provided
      authentication at the higher taxonomic levels. These diagnostics indel marker
      from trnH-psbA were successful in identifying different species (5 out of 7)
      within the studied Citrus except Citrus limon and Citrus medica. These two
      closely related species are distinguished through the 6 bp deletion in trnL-trnF.
      This study demonstrated that the indel polymorphism based approach easily
      characterizes the Citrus species and the same may be applied in other complex
      groups. Likewise other indels occurring intergenic spacer of chloroplast regions
      may be tested for rapid identification of other secondary citrus species. 

PMID- 25048293
TI  - Hydrogenation of imines catalyzed by trisphosphine-substituted molybdenum and
      tungsten nitrosyl hydrides and co-catalytic acid.
AB  - Hydride complexes Mo,W(CO)(NO)H(mer-etp(i)p) (iPr2PCH2CH2)2PPh=etp(i)p) (2
      a,b(syn), syn and anti of NO and Ph(etp(i)p) orientions) were prepared and probed
      in imine hydrogenations together with co-catalytic [H(Et2O)2][B(C6F5)4] (140 
      degrees C, 60 bar H2). 2 a,b(syn) were obtained via reduction of syn/anti
      Mo,W(NO)Cl3(mer-etp(i)p) and syn,anti-Mo,W(NO)(CO)Cl(mer-etp(i)p).
      [H(Et2O)2][B(C6F5)4] in THF converted the hydrides into THF complexes syn
      [Mo,W(NO)(CO)(etp(i)p)(THF)][B(C6F5)4]. Combinations of the p-substituents of
      aryl imines p-R(1)C6H4CH=N-p-C6H4R(2) (R(1),R(2)=H,F,Cl,OMe,alpha-Np) were
      hydrogenated to amines (maximum initial TOFs of 1960 h(-1) (2 a(syn)) and 740 h(
      1) (2 b(syn)) for N-(4-methoxybenzylidene)aniline). An 'ionic hydrogenation'
      mechanism based on linear Hammett plots (rho=-10.5, p-substitution on the C-side
      and rho=0.86, p-substitution on the N-side), iminium intermediates, linear P(H2)
      dependence, and DKIE=1.38 is proposed. Heterolytic splitting of H2 followed by
      'proton before hydride' transfers are the steps in the ionic mechanism where H2
      ligand addition is rate limiting.

PMID- 25048294
TI  - Combined scanning transmission X-ray and electron microscopy for the
      characterization of bacterial endospores.
AB  - Endospores (also referred to as bacterial spores) are bacterial structures formed
      by several bacterial species of the phylum Firmicutes. Spores form as a response
      to environmental stress. These structures exhibit remarkable resistance to harsh
      environmental conditions such as exposure to heat, desiccation, and chemical
      oxidants. The spores include several layers of protein and peptidoglycan that
      surround a core harboring DNA as well as high concentrations of calcium and
      dipicolinic acid (DPA). A combination of scanning transmission X-ray microscopy,
      scanning transmission electron microscopy, and energy dispersive spectroscopy was
      used for the direct quantitative characterization of bacterial spores. The
      concentration and localization of DPA, Ca(2+) , and other elements were
      determined and compared for the core and cortex of spores from two distinct
      genera: Bacillus subtilis and Desulfotomaculum reducens. This micro-spectroscopic
      approach is uniquely suited for the direct study of individual bacterial spores,
      while classical molecular and biochemical methods access only bulk
      characteristics. 

PMID- 25048295
TI  - Income-related inequalities in chronic conditions, physical functioning and
      psychological distress among older people in Australia: cross-sectional findings
      from the 45 and up study.
AB  - BACKGROUND: The burden of chronic disease continues to rise as populations age.
      There is relatively little published on the socioeconomic distribution of this
      burden in older people. This study quantifies absolute and relative income
      related inequalities in prevalence of chronic diseases, severe physical
      functioning limitation and high psychological distress in mid-age and older
      people in Australia. METHODS: Cross-sectional study of 208,450 participants in
      the 45 and Up Study, a population-based cohort of men and women aged 45-106 years
      from New South Wales, Australia. Chronic conditions included self-reported heart
      disease, diabetes, Parkinson's disease, cancer and osteoarthritis; physical
      functioning limitation (severe/not) was measured using Medical Outcomes Study
      measures and psychological distress (high/not) using the Kessler Psychological
      Distress Scale. For each outcome, prevalence was estimated in relation to annual
      household income (6 categories). Prevalence differences (PDs) and ratios (PRs)
      were generated, comparing the lowest income category (< $20,000) to the highest
      (>= $70,000), using Poisson regression with robust standard errors, weighted for
      age, sex and region of residence. Analyses were stratified by age group (45-64,
      65-79 and >= 80 years) and sex and adjusted for age and country of birth.
      RESULTS: With few exceptions, there were income gradients in the prevalence of
      chronic conditions among all age-sex groups, with prevalence decreasing with
      increasing income. Of the chronic diseases, PDs were highest for diabetes
      (ranging between 5.69% and 10.36% across age-sex groups) and in women, also for
      osteoarthritis (5.72% to 8.14%); PRs were highest for osteoarthritis in men aged
      45-64 years (4.01), otherwise they were highest for diabetes (1.78 to 3.43).
      Inequalities were very high for both physical functioning limitation and
      psychological distress, particularly among those aged 45-64 (PDs between 18.67%
      and 29.23% and PRs between 4.63 and 16.51). Absolute and relative inequalities
      tended to decrease with age, but remained relatively high for diabetes and
      physical functioning in the elderly (>= 80 years). CONCLUSIONS: Significant
      inequalities in the prevalence of chronic conditions, physical functioning and
      psychological distress persist into old age. The additional health burden placed
      on those who are already disadvantaged is likely to become an increasingly
      important issue in an ageing population.

PMID- 25048296
TI  - The regional distribution of anxiety disorders: implications for the Global
      Burden of Disease Study, 2010.
AB  - Anxiety disorders are increasingly acknowledged as a global health issue however
      an accurate picture of prevalence across populations is lacking. Empirical data
      are incomplete and inconsistent so alternate means of estimating prevalence are
      required to inform estimates for the new Global Burden of Disease Study 2010. We
      used a Bayesian meta-regression approach which included empirical epidemiological
      data, expert prior information, study covariates and population characteristics.
      Reported are global and regional point prevalence for anxiety disorders in 2010.
      Point prevalence of anxiety disorders differed by up to three-fold across world
      regions, ranging between 2.1% (1.8-2.5%) in East Asia and 6.1% (5.1-7.4%) in
      North Africa/Middle East. Anxiety was more common in Latin America; high income
      regions; and regions with a history of recent conflict. There was considerable
      uncertainty around estimates, particularly for regions where no data were
      available. Future research is required to examine whether variations in regional
      distributions of anxiety disorders are substantive differences or an artefact of
      cultural or methodological differences. This is a particular imperative where
      anxiety is consistently reported to be less common, and where it appears to be
      elevated, but uncertainty prevents the reporting of conclusive estimates.

PMID- 25048297
TI  - Stress-responsive regulation of mitochondria through the ER unfolded protein
      response.
AB  - The endoplasmic reticulum (ER) and mitochondria form physical interactions
      involved in the regulation of biologic functions including mitochondrial
      bioenergetics and apoptotic signaling. To coordinate these functions during
      stress, cells must coregulate ER and mitochondria through stress-responsive
      signaling pathways such as the ER unfolded protein response (UPR). Although the
      UPR is traditionally viewed as a signaling pathway responsible for regulating ER
      proteostasis, it is becoming increasingly clear that the protein kinase RNA (PKR)
      like endoplasmic reticulum kinase (PERK) signaling pathway within the UPR can
      also regulate mitochondria proteostasis and function in response to pathologic
      insults that induce ER stress. Here, we discuss the contributions of PERK in
      coordinating ER-mitochondrial activities and describe the mechanisms by which
      PERK adapts mitochondrial proteostasis and function in response to ER stress.

PMID- 25048298
TI  - Heterologous expression of Ceratophyllum demersum phytochelatin synthase, CdPCS1,
      in rice leads to lower arsenic accumulation in grain.
AB  - Recent studies have identified rice (Oryza sativa) as a major dietary source of
      inorganic arsenic (As) and poses a significant human health risk. The predominant
      model for plant detoxification of heavy metals is complexation of heavy metals
      with phytochelatins (PCs), synthesized non-translationally by PC synthase (PCS)
      and compartmentalized in vacuoles. In this study, in order to restrict As in the
      rice roots as a detoxification mechanism, a transgenic approach has been followed
      through expression of phytochelatin synthase, CdPCS1, from Ceratophyllum
      demersum, an aquatic As-accumulator plant. CdPCS1 expressing rice transgenic
      lines showed marked increase in PCS activity and enhanced synthesis of PCs in
      comparison to non-transgenic plant. Transgenic lines showed enhanced accumulation
      of As in root and shoot. This enhanced metal accumulation potential of transgenic
      lines was positively correlated to the content of PCs, which also increased
      several-fold higher in transgenic lines. However, all the transgenic lines
      accumulated significantly lower As in grain and husk in comparison to non
      transgenic plant. The higher level of PCs in transgenic plants relative to non
      transgenic presumably allowed sequestering and detoxification of higher amounts
      of As in roots and shoots, thereby restricting its accumulation in grain. 

PMID- 25048299
TI  - Detecting disease variants in case-parent trio studies using the bioconductor
      software package trio.
AB  - Case-parent trio studies are commonly employed in genetics to detect variants
      underlying common complex disease risk. Both commercial and freely available
      software suites for genetic data analysis usually contain methods for case-parent
      trio designs. A user might, however, experience limitations with these packages,
      which can include missing functionality to extend the software if a desired
      analysis has not been implemented, and the inability to programmatically capture
      all the software versions used for low-level processing and high-level inference
      of genomic data, a critical consideration in particular for high-throughput
      experiments. Here, we present a software vignette (i.e., a manual with step by
      step instructions and examples to demonstrate software functionality) for
      reproducible genome-wide analyses of case-parent trio data using the open source
      Bioconductor package trio. The workflow for the practitioner uses data from
      previous genetic trio studies to illustrate functions for marginal association
      tests, assessment of parent-of-origin effects, power and sample size
      calculations, and functions to detect gene-gene and gene-environment interactions
      associated with disease. 

PMID- 25048301
TI  - Hepatocellular carcinoma. Treatment potential of targeting Toll-like receptors in
      HCC.

PMID- 25048303
TI  - Crohn's disease. TCF1 regulates Paneth cell alpha-defensins.

PMID- 25048307
TI  - Clinicopathological associations in temporal lobe epilepsy patients utilising the
      current ILAE focal cortical dysplasia classification.
AB  - OBJECTIVES: This study utilised the revised 2011 ILAE classification of focal
      cortical dysplasia (FCD) (Blumcke et al., 2011) to examine pathology in a cohort
      of children and adults who underwent temporal lobe epilepsy (TLE) surgery, and to
      describe the electroclinical and imaging features associated with these
      pathologies. METHODS: The sample population were children (n=26) and adults
      (n=47) who underwent TLE surgery between 2002 and 2011 at our institutions.
      Neuropathology and MRI studies were re-reviewed by experts blinded to the
      original diagnosis. EEG and clinical data including current seizure outcome were
      determined by patient file review and/or patient contact. Pre-operative data,
      post-operative outcome and pathological diagnoses were compared. RESULTS: The
      commonest pathology in the adult cohort was isolated hippocampal sclerosis (HS)
      (n=24, 51.1%) and in the paediatric cohort, isolated tumour (n=10, 38.5%).
      Overall, HS with associated FCD (FCD IIIA) was the third most common pathology
      (n=12, 16.4%). Temporal grey matter signal changes on MRI were associated with
      FCD IIIA (p=0.035). FCD IIIA had the poorest post-surgical seizure outcome
      compared to all other pathologies (p=0.026). A history of bilateral convulsive
      seizures was more common in adults (n=40, p<0.0005), and was associated with
      failure to achieve postoperative seizure freedom (p=0.045). Postoperatively,
      paediatric TLE had higher rates of seizure freedom (p=0.005) and more children
      had ceased medication (p<0.0005). SIGNIFICANCE: FCD IIIA is a comparatively
      common pathological subtype in TLE, with a poor post-surgical outcome. Pre
      operative recognition of FCD IIIA may be feasible through grey matter signal
      change on MRI. Paediatric patients had a higher rate of seizure freedom than
      adults. Pre-operative bilateral convulsive seizures were associated with poor
      outcome after surgery.

PMID- 25048306
TI  - Sociogenomics of self vs. non-self cooperation during development of
      Dictyostelium discoideum.
AB  - BACKGROUND: Dictyostelium discoideum, a microbial model for social evolution, is
      known to distinguish self from non-self and show genotype-dependent behavior
      during chimeric development. Aside from a small number of cell-cell recognition
      genes, however, little is known about the genetic basis of self/non-self
      recognition in this species. Based on the key hypothesis that there should be
      differential expression of genes if D. discoideum cells were interacting with non
      clone mates, we performed transcriptomic profiling study in this species during
      clonal vs. chimeric development. The transcriptomic profiles of D. discoideum
      cells in clones vs. different chimeras were compared at five different
      developmental stages using a customized microarray. Effects of chimerism on
      global transcriptional patterns associated with social interactions were
      observed. RESULTS: We find 1,759 genes significantly different between chimera
      and clone, 1,144 genes associated significant strain differences, and 6,586 genes
      developmentally regulated over time. Principal component analysis showed a small
      amount of the transcriptional variance to chimerism-related factors (Chimerism:
      0.18%, Chimerism * Timepoint: 0.03%). There are 162 genes specifically regulated
      under chimeric development, with continuous small differences between chimera vs.
      clone over development. Almost 60% of chimera-associated differential genes were
      differentially expressed at the 4 h aggregate stage, which corresponds to the
      initial transition of D. discoideum from solitary life to a multicellular phase.
      CONCLUSIONS: A relatively small proportion of over-all variation in gene
      expression is explained by differences between chimeric and clonal development.
      The relatively small modifications in gene expression associated with chimerism
      is compatible with the high level of cooperation observed among different strains
      of D. discoideum; cells of distinct genetic backgrounds will co-aggregate
      indiscriminately and co-develop into fruiting bodies. Chimeric development may
      involve re-programming of the transcriptome through small modifications of the
      developmental genetic network, which may also indicate that response to social
      interaction involves many genes with individually small transcriptional effect.

PMID- 25048309
TI  - Vocational rehabilitation service patterns and employment outcomes of people with
      epilepsy.
AB  - This study aimed to examine the association between vocational rehabilitation
      (VR) services and employment outcomes of people with epilepsy (PWE), after
      controlling for demographic covariates. Data was retrieved from the
      Rehabilitation Services Administration Case Service Report (RSA-911) database for
      fiscal year (FY) 2011. Multivariate logistic regression was used to predict
      employment outcomes of PWE. Of the 2030 previously unemployed PWE who received
      services, 884 (43.5%) achieved successful competitive employment. Results
      indicate that higher education level and cost of VR services consumed were
      positively related to successful employment. In contrast, having co-occurring
      anxiety/depression, receiving cash benefits, or increasing time spent in the VR
      system was negatively associated with employment. Eight specific VR services
      (e.g., education, vocational training, and job search and placement assistance)
      were also found to be significant predictors of employment. Services provided by
      state VR agencies were proven to be beneficial in improving employment outcomes.
      PWE should be encouraged to pursue VR services to increase the chances of
      attaining employment. Health care providers should also become familiar with the
      array of VR services. 

PMID- 25048308
TI  - Brain morphometry of Dravet syndrome.
AB  - The aim of this study was to identify differential global and local brain
      structural patterns in Dravet Syndrome (DS) patients as compared with a control
      subject group, using brain morphometry techniques which provide a quantitative
      whole-brain structural analysis that allows for specific patterns to be
      generalized across series of individuals. Nine patients with the diagnosis of DS
      that tested positive for mutation in the SCN1A gene and nine well-matched healthy
      controls were investigated using voxel brain morphometry (VBM), cortical
      thickness and cortical gyrification measurements. Global volume reductions of
      gray matter (GM) and white matter (WM) were related to DS. Local volume
      reductions corresponding to several white matter regions in brainstem,
      cerebellum, corpus callosum, corticospinal tracts and association fibers (left
      inferior fronto-occipital fasciculus and left uncinate fasciculus) were also
      found. Furthermore, DS showed a reduced cortical folding in the right precentral
      gyrus. The present findings describe DS-related brain structure abnormalities
      probably linked to the expression of the SCN1A mutation. 

PMID- 25048310
TI  - High dose (4 mg/kg/day) versus usual dose (2 mg/kg/day) oral prednisolone for
      treatment of infantile spasms: an open-label, randomized controlled trial.
AB  - OBJECTIVES: This study aimed to test the hypothesis that high-dose prednisolone
      (4 mg/kg/day) may be more efficacious than usual-dose (2 mg/kg/day) prednisolone
      for spasm resolution at 14-days in children with infantile spasms. METHODS: This
      was a randomized, open-label-trial conducted at a tertiary-level-hospital from
      February-2012 to March-2013. Children aged 3-months to 2-years presenting with
      infantile spasms in clusters (at least 1 cluster/day) with hypsarrhythmia or its
      variants on EEG were enrolled. The study participants were randomized to receive
      either high-dose prednisolone (4 mg/kg/day) or the usual-dose (2 mg/kg/day)
      prednisolone. The primary outcome measure was the proportion of children who
      achieved spasm freedom for 48-h at day-14 after treatment initiation as per
      parental reports in both the groups. The adverse effects were also monitored. The
      study was registered with the clinicaltrials.gov (ClinicalTrials.gov Identifier:
      NCT01575639). RESULTS: Sixty-three children were randomized into the two groups
      with comparable baseline characteristics. The proportion of children with spasm
      cessation on day-14 was significantly higher in the high-dose group as compared
      to the usual-dose group (51.6% vs. 25%, p=0.03). The absolute risk reduction was
      26.6% (95% confidence interval 11.5-41.7%) with number needed to treat being 4.
      The adverse effects were comparable in both the groups. CONCLUSIONS: High-dose
      prednisolone (4 mg/kg/d) was more effective than low-dose prednisolone (2mg/kg/d)
      in achieving spasm cessation at 14-days (as per parental reports) in children
      with infantile spasms.

PMID- 25048312
TI  - A randomized, placebo-controlled study of a new sublingual formulation of
      fentanyl citrate (fentanyl ethypharm) for breakthrough pain in opioid-treated
      patients with cancer.

PMID- 25048311
TI  - Preliminary study of light-cured hydrogel for endodontic drug delivery vehicle.
AB  - AIM: Direct pulp capping is the treatment of an exposed vital pulp with a dental
      material to facilitate the formation of reparative dentin and maintenance of
      vital pulp. A bioengineered drug delivery vehicle has the potential to increase
      the success rate of pulp capping. The aim of this study was to develop an
      injectable and light-curing drug delivery vehicle for endodontic treatment
      including direct pulp capping. METHODS: Polyethylene glycol-maleate-citrate
      (PEGMC) hydrogel was synthesized as a drug delivery vehicle that is composed of
      PEGMC (45% w/v), acrylic acid (AA) (5% w/v), 2,2'-azobis(2-methylpropionamidine)
      dihydrochloride (AAPH) (0.1% w/v), and deionized water. The association between
      prehydrogel-solution volume and visible light-curing was examined. The
      cytotoxicity of the hydrogel was tested using L929 cells in a cell culture
      system. Ca(2+) release from the hydrogel was determined using calcium hydroxide
      as the incorporated medicine. RESULTS: The results showed that the light-curing
      time for hydrogel is comparable to composite resin. The hydrogel had cell
      toxicity similar to adhesive systems. Moreover, controlled Ca(2+) release was
      obtained from the calcium hydroxide incorporated hydrogel. CONCLUSIONS: The data
      suggest that hydrogel should be explored further as a promising drug delivery
      vehicle for vital pulp therapy and regenerative endodontics.

PMID- 25048314
TI  - 12th European Biological Inorganic Chemistry Conference, Zurich, Switzerland,
      August 24-28, 2014. Preface.

PMID- 25048315
TI  - EuroBIC Medal 2014.

PMID- 25048330
TI  - Coherent spin transport and suppression of spin relaxation in InSb nanowires with
      single subband occupancy at room temperature.
AB  - A longstanding goal of spintronics is to inject, then coherently transport, and
      finally detect electron spins in a semiconductor nanowire in which a single
      quantized subband is occupied by the electrons at room temperature. Here, the
      achieving of this goal in electrochemically self-assembled 50-nm diameter InSb
      nanowires is reported and substantiated by demonstrating both the spin-valve
      effect and the Hanle effect. Observing both effects in the same sample allows one
      to estimate the electron mobility and the spin relaxation time in the nanowires.
      It is found that despite four orders of magnitude degradation in the mobility
      compared to bulk or quantum wells and a resulting four orders of magnitude
      increase in the Elliott-Yafet spin relaxation rate, the spin relaxation time in
      the nanowires is still about an order of magnitude longer than what has been
      reported in bulk and quantum wells. This is caused by the elimination or
      suppression of the D'yakonov-Perel' spin relaxation through single subband
      occupancy. These experiments shed light on the nature of spin transport in a true
      quantum wire and raise hopes for the realization of a room-temperature Datta-Das
      spin transistor, where single subband occupancy is critical for optimum
      performance. 

PMID- 25048332
TI  - Personal experience and observations on photodynamic therapy (PDT) for columnar
      epithelial lined (Barrett's) oesophagus and its neoplastic evolution.

PMID- 25048331
TI  - TIMP-1 in patients with cirrhosis: relation to liver dysfunction, portal
      hypertension, and hemodynamic changes.
AB  - OBJECTIVE: Cirrhotic portal hypertensive patients often develop hemodynamic
      complications and the diagnosis is often based on liver biopsy and measurements
      of the hepatic venous pressure gradient (HVPG). Potential noninvasive biomarkers
      for the severity of cirrhosis are the matrix metalloproteinase and their specific
      inhibitors such as tissue inhibitor of metalloproteinases-1 (TIMP-1). The aim of
      the study was to investigate TIMP-1 levels in cirrhosis in relation to the degree
      of liver dysfunction, portal hypertension, and hemodynamic changes. MATERIALS AND
      METHODS: We retrospectively studied 84 patients with cirrhosis and 14 controls
      without liver disease. All individuals underwent a liver vein catheterization
      with a hemodynamic assessment. TIMP-1 was determined in arterial and hepatic
      venous plasma using an MAC-15 TIMP-1 ELISA. RESULTS: Hepatic venous
      concentrations of TIMP-1 were significantly increased in patients compared to
      controls: 336 (166) ng/ml versus 145 (100) (median/IQ range) (p < 0.001) with a
      progressive increase throughout the Child classes (p < 0.001). Circulating TIMP-1
      correlated significantly with indocyanine green clearance (r = -0.44, p <
      0.0001), Child Turcotte score (r = 0.50, p < 0.0001), HVPG (r = 0.40, p <
      0.0001), mean arterial pressure (r = -0.29, p = 0.008), and systemic vascular
      resistance (r = -0.23, p = 0.03). Receiver operating characteristic curve
      analysis enabled us to establish cutoff values for TIMP-1 with regard to portal
      hypertension. CONCLUSIONS: TIMP-1 is significantly increased in patients with
      cirrhosis and correlates with the severity of the disease, degree of portal
      hypertension, and vasodilatory state. TIMP-1 is therefore a promising new
      noninvasive marker to predict hemodynamic-related complications in cirrhosis.

PMID- 25048333
TI  - Photodynamic therapy for dysplastic Barrett's oesophagus and early cancer.
AB  - BACKGROUND: Cancer in the columnar-lined oesophagus develops through a multi-step
      process initiated by chronic gastro-oesophageal reflux progressing through
      metaplasia, low-grade dysplasia to high-grade dysplasia, which currently remains
      the best marker of cancer risk. Destruction of dysplasia using photodynamic
      therapy and other endoscopic methods may prevent cancer development. METHODS AND
      RESULTS: The potential problem in the columnar-lined oesophagus is surface
      limited to a depth of 0.6mm. Re-surfacing the oesophagus eradicates the disease
      and offers the possible prevention of progression. Mucosal ablation with lasers,
      electro- and argon plasma coagulators, photodynamic therapy and endoscopic
      mucosal resection can remove dysplasia and allow regeneration of neo-squamous
      mucosa following acid reflux control usually with high-dose proton pump inhibitor
      therapy. Endoscopic mucosal resection is very effective when there is a localised
      visible mucosal abnormality. Multifocal dysplasia carries a greater chance of
      malignant degeneration, and photodynamic therapy is more useful for widespread
      and potentially extensive disease. The only randomised partially blinded trial
      for prevention of cancer in Barrett's oesophagus has demonstrated a significant
      reduction in cancer progression following endoscopic photodynamic therapy.
      CONCLUSIONS: A multimodal approach to the management of dysplasia in Barrett's
      oesophagus is necessary combining endoscopic mucosal resection, photodynamic
      therapy and thermal ablation. Currently dysplastic Barrett's is the major target
      of therapy, the treatment of metaplasia should currently be part of an
      investigative study.

PMID- 25048334
TI  - Barrett's oesophagus and photodynamic therapy (PDT).
AB  - Barrett's oesophagus is a precursor of oesophageal adenocarcinoma. This cancer
      has the fastest growing incidence of any solid tumour in the Western world.
      Surveillance of Barrett's oesophagus is routinely undertaken to detect early
      malignant transformation. However, ablative endoscopic treatments are available
      and these can obliterate the abnormal epithelium, allowing neo-squamous re
      growth. Photodynamic therapy (PDT) using haematoporphyrin derivative
      (HpD)/porfimer sodium (Photofrin((r))), m-tetrahydroxyphenyl chlorin (mTHPC) and
      5-aminolaevulinic acid (ALA) utilise such a technique. In this non-thermal method
      of ablation, the photosensitisers, together with light and oxygen, produce local
      tissue destruction. The use of PDT ablation of Barrett's oesophagus is reviewed. 

PMID- 25048335
TI  - Photodynamic therapy in dermatology: Dundee clinical and research experience.
AB  - Topical photodynamic therapy (PDT) is increasingly accepted and used as a highly
      effective treatment for superficial non-melanoma skin cancer and dysplasia. We
      describe the developments in topical PDT for the treatment of skin diseases in
      our own PDT Centre in Dundee, both clinically and from a research base.
      Improvements in PDT could be achieved by optimisation of photosensitiser and
      light delivery, and these goals underpin the aims of our centre. We hope to
      facilitate the dissemination of use of PDT in dermatology throughout Scotland and
      outline some of the progress in these areas. 

PMID- 25048336
TI  - Photodynamic therapy for Bowen's disease and squamous cell carcinoma of the skin.
AB  - BACKGROUND: Photodynamic therapy involves the activation by visible light of a
      previously administered photosensitizing agent in order to cause tumor necrosis.
      Skin tumors can be treated with topical photosensitizers and thus avoiding
      systemic side effects. In this study we evaluate the immediate and long-term
      effects of photodynamic therapy (PDT), using aminolevulinic acid (ALA) as a
      photosensitizer and a non-laser light source, on Bowen's disease (intra
      epithelial squamous cell carcinoma) and on frank squamous cell carcinoma (SCC) of
      the skin. METHODS: ALA in cream form (20%) was topically applied on biopsy-proven
      Bowen's disease or SCC of the skin. The lesions were covered with occlusive and
      light-shielding dressing. Sixteen hours later, they were submitted to a 10-min
      light session using Versa-LightTM, a non-laser light source (spectral output of
      580-720nm and 1250-1600nm, 100J/cm(2)). The initial evaluation was done 21 days
      post-treatment and every 3m thereafter. Patients that did not respond to
      treatment after two to three sessions were referred to surgery. RESULTS: Forty
      Bowen's disease lesions (24 patients) and 43 SCC lesions (18 patients) underwent
      treatment. Median follow-up was 21+/-8m. No patient had any remarkable side
      effects. Thirty-four Bowen's disease (85%) lesions completely responded as did 32
      SCC lesions (74%). CONCLUSIONS: Our findings showed that PDT is highly effective
      in treating Bowen's disease and SCC lesions and can be used as a first treatment
      modality in so far as its use does not preclude the subsequent surgery
      recommended for the small percentage of failures.

PMID- 25048337
TI  - An investigation into the potential of phenothiazinium-based photo-sensitisers to
      act as PDT agents.
AB  - BACKGROUND: There is an urgent need for effective cancer treatments and
      increasingly, photo-dynamic therapy (PDT) is being used to fulfil this need as it
      offers a number of advantages over traditional cancer treatments. Here, the
      potential of a series of phenothiazinium-based photo-sensitisers (PhBPs) as PDT
      agents is tested. METHODS: PhBPs were incubated with EMT-6 tumour cells and
      erythrocytes respectively under dark and light conditions (3.15Jcm(-2) over
      30min). "Comet assay" and haemolytic assay were then used to assess cellular
      photo-damage induced by these PhBPs. Additionally, in vitro assays were used to
      determine light adsorption characteristics, singlet oxygen yields (PhiDeltaPhBP)
      and lipophilicity (logP) of these PhBPs. RESULTS: "Comet assay" showed EMT-6
      incubation with PhBPs under light conditions to produce DNA "tails", which were
      circa 35MUm long, indicating the presence of DNA photo-damage. Corresponding
      incubations under dark conditions led to no such damage. The majority of the
      PhBPs tested possessed significant singlet oxygen yields (PhiDeltaPhBP>0.7),
      suggesting the general use of type II mechanisms for photo-sensitization, and
      were generally lipophilic (logP>0). Incubation of erythrocytes with these PhBPs
      in the dark produced between 6% and 19% haemolysis. These levels were generally
      unaffected by illumination except in the case of DMMB, which showed haemolytic
      levels increasing from 11% to 61%. CONCLUSIONS: It is suggested that DNA may be
      the primary target for the photo-dynamic anti-tumour activity of the PhBPs tested
      with the exception of DMMB, which may potentially also target tumour cell
      membranes.

PMID- 25048338
TI  - Combined treatment of urinary bladder cancer with the use of photodynamic therapy
      (PDT) and subsequent BCG-therapy: a pilot study.
AB  - INTRODUCTION: Transitional cell carcinoma (TCC) of the urinary bladder is
      nowadays one of the most common cancers in young men. Similarly to other cancers
      TCC can be treated with curative intent when it is diagnosed very early. In
      recent years there has been an intensive development of treatment methods of
      urological diseases based on modern scientific discoveries, one of which is
      photodynamic therapy (PDT). This treatment in urology may be used either for pre
      cancerous lesions, carcinoma in situ or for superficial tumours. PATIENTS AND
      METHODS: In this study, patients were subjected to PDT with subsequent BCG
      therapy. In our study we demonstrate cases of 14 patients, who were under
      observation for minimum 24 months. All patients were diagnosed as having TCC in
      pathological stage pT1N0M0 (clinical: T1NxM0). They had previously undergone
      transurethral resection of bladder tumour (TUR-BT) and no exophytic tumours were
      observed. Patients were instillated intravesically with 4.5g of ALA
      (aminolevulinic acid) in buffered solution in the bladder for 2h. Afterwards,
      within 2h the bladder was irradiated with 635nm an argon-pumped dye laser light.
      Light power on the tip of the fibre was 1.0W. The total energy dose was 2000J
      equally divided into two to three sessions. RESULTS: After 24-month observation
      total response was observed in eight patients (in histopathological examination
      urocystitis was diagnosed), partial response (low- or high-grade dysplasia in
      microscopic examination) in two patients and no response in four patients (cancer
      cells in excised specimens). CONCLUSIONS: :

PMID- 25048339
TI  - Practical issues in autofluorescence bronchoscopy with Storz D Light
      bronchoscope.
AB  - Practical aspects of Storz Dlight autofluorescence bronchoscopy are presented
      from a series of 73 patients. 80 biopsies were taken of which 23 had at least
      moderate dysplasia, including 8 CIS lesions. Causes of false positive
      fluorescence abnormalities were suction trauma, overlying mucus, depressions in
      the leading edge of bronchial spurs, and flexion points of spurs. Positive
      predictive value of a significant fluorescence abnormality was 56%. The highest
      yield was in those patients with prior ENT malignancy. 

PMID- 25048340
TI  - Photodynamic therapy (PDT) for lung cancer: the Yorkshire Laser Centre
      experience.
AB  - BACKGROUND: The Yorkshire Laser Centre team have been engaged in photodynamic
      therapy (PDT) since 1990. In this article we review our experience in
      bronchoscopic PDT for lung cancer and outline our current indications and
      results. METHODS: 160 patients in 2 groups entered into a prospective study:
      Group A (N=144) were symptomatic with advanced inoperable disease and with
      presence of >50% bronchial obstruction. Group E (N=16) with early stage cancer
      and presence of superficial lesion confined to bronchial tree. All patients had
      standard investigation and work-up bronchoscopy and biopsy confirmation of cancer
      by cyto-histology. PDT method was intravenous administration of 2mg/kg BW of
      Photofrin (Porfimer Sodium) followed by bronchoscopic illumination of 630nm laser
      light. RESULTS: There was no treatment-related mortality. Nine patients (5.6%)
      presented with skin photosensitivity reaction and another eight with respiratory
      complication. Group A: Symptom relief was achieved in all. This was matched by
      significant improvement in bronchial opening (58.1%). Survival was 9.6 months
      (mean) and 5 months (median), respectively. This was greater in patients with
      better performance status and lower stage of disease. Group E: Every patient had
      a complete response to treatment, some after two treatments. Survival in this
      group was 75.4 months (mean) and 69 months (median). CONCLUSIONS: Bronchoscopic
      PDT is indicated in both advanced and early stage lung cancer. In the former it
      provides symptomatic relief in all and survival benefit in some; in the latter it
      achieves long survival and potential cure.

PMID- 25048341
TI  - Significant association of deficiencies of hemoglobin, iron, vitamin B12, and
      folic acid and high homocysteine level with recurrent aphthous stomatitis.
AB  - BACKGROUND: A portion of patients with recurrent aphthous stomatitis (RAS) may
      have nutritional deficiency. This study evaluated whether there was an intimate
      association of the deficiencies of hemoglobin, iron, vitamin B12, and folic acid
      and high blood homocysteine level with RAS. METHODS: The blood hemoglobin, iron,
      vitamin B12, folic acid, and homocysteine concentrations in 273 RAS patients were
      measured and compared with the corresponding levels in 273 age- and sex-matched
      healthy control subjects. RESULTS: We found that 57 (20.9%), 55 (20.1%), 13
      (4.8%), and 7 (2.6%) RAS patients had deficiencies of hemoglobin (Men < 13 g/dl,
      Women < 12 g/dl), iron (<60 MUg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4
      ng/ml), respectively. Moreover, 21 (7.7%) RAS patients had abnormally high blood
      homocysteine level. RAS patients had a significantly higher frequency of
      hemoglobin, iron, vitamin B12, or folic acid deficiency and of abnormally
      elevated blood homocysteine level than healthy control subjects (all P-values =
      0.000 except for folic acid P = 0.022). If 273 RAS patients were further divided
      into 32 patients with major-typed RAS (MjRAS) and 241 patients with minor-typed
      RAS (MiRAS), we found that male MjRAS patients had a significantly lower mean
      hemoglobin concentration than MiRAS patients (P = 0.021), but MjRAS patients had
      a significantly higher mean homocysteine level than MiRAS patients (P = 0.000).
      CONCLUSION: We conclude that there is a significant association of deficiencies
      of hemoglobin, iron, vitamin B12, and folic acid and abnormally high blood
      homocysteine level with RAS.

PMID- 25048342
TI  - Effects of protein in wheat flour on retrogradation of wheat starch.
AB  - Albumins, globulins, gliadins, and glutenins were isolated from wheat flour and
      the effects of those proteins on retrogradation of wheat starch were
      investigated. The results showed that only glutenins retarded retrogradation of
      wheat starch and other 3 proteins promoted it. The results of IR spectra proved
      that no S-S linkage formed during retrogradation of wheat starch blended with
      wheat proteins. Combination of wheat starch and globulins or gliadins through
      glucosidic bonds hindered the hydrolysis of wheat starch by alpha-amylase. The
      melting peak temperatures of retrograded wheat starch attached to different
      proteins were 128.46, 126.14, 132.03, 121.65, and 134.84  degrees C for the
      control with no protein, albumins, glutenins, globulins, gliadins groups,
      respectively, and there was no second melting temperature for albumins group.
      Interaction of wheat proteins and starch in retrograded wheat starch greatly
      decreased the endothermic enthalpy (?H) of retrograded wheat starch. Retrograded
      wheat starch bound to gliadins might be a new kind of resistant starch based on
      glycosidic bond between starch and protein. 

PMID- 25048343
TI  - Temporal trends in the occurrence and outcomes of atrial fibrillation in patients
      with acute myocardial infarction (from the Atherosclerosis Risk in Communities
      Surveillance Study).
AB  - Atrial fibrillation (AF) frequently coexists in the setting of myocardial
      infarction (MI), being associated with increased mortality. Nonetheless, temporal
      trends in the occurrence of AF complicating MI and in the prognosis of these
      patients are not well described. We examined temporal trends in prevalence of AF
      in the setting of MI and the effect of AF on prognosis in the community. We
      studied a population-based sample of 20,049 validated first-incident nonfatal
      hospitalized MIs among 35- to 74-year old residents of 4 communities in the
      Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 2009.
      Prevalence of AF in the setting of MI increased from 11% to 15% during the 23
      year study period. The multivariable adjusted odds ratio for prevalent AF, per 5
      year increment, was 1.11 (95% confidence interval 1.04 to 1.19). Overall, in
      patients with MI, AF was associated with increased 1-year case fatality (odds
      ratio 1.47, 95% confidence interval 1.07 to 2.01) compared with those without AF.
      However, there was no evidence that the impact of AF on MI survival changed over
      time or differed over time by sex, race, or MI classification (all p values
      >0.10). In conclusion, co-occurrence of AF in MI slightly increased between 1987
      and 2009. The adverse impact of AF on survival in the setting of MI was
      consistent throughout. In the setting of MI, co-occurrence of AF should be viewed
      as a critical clinical event, and treatment needs unique to this population
      should be explored further. 

PMID- 25048344
TI  - Comparison by optical coherence tomography of the frequency of lipid coronary
      plaques in current smokers, former smokers, and nonsmokers.
AB  - Smoking is associated with high incidence of cardiovascular events including
      acute coronary syndrome. We sought to characterize coronary plaques in patients
      with ongoing smoking using optical coherence tomography (OCT) compared with
      former smokers and nonsmokers. We identified 465 coronary plaques from 182
      subjects who underwent OCT imaging for all 3 coronary arteries. Subjects were
      divided into 3 groups: current smokers (n = 41), former smokers (n = 67), and
      nonsmokers (n = 74). OCT analysis included the presence of lipid-rich plaque,
      thin-cap fibroatheroma (TCFA), calcification, maximum lipid arc, lipid core
      length, lipid index, and fibrous cap thickness. Lipid index was defined by mean
      lipid arc multiplied by lipid core length. Compared with former smokers and
      nonsmokers, the incidence of lipid plaques and TCFA was significantly higher in
      current smokers (lipid plaques: 68.0% vs 45.9% and 52.6%, p = 0.002; TCFA: 18.4%
      vs 7.6% and 9.9%, p = 0.018). There was a trend for higher plaque disruption in
      current smokers. Former smokers were more likely to have calcified plaques than
      current and nonsmokers (52.9% vs 32.0% and 38.0%, p = 0.001). In a multivariate
      analysis, current smoking, low-density lipoprotein, and presentation with acute
      coronary syndrome were independently associated with the presence of TCFAs. In
      conclusion, current smokers are more likely to have lipid plaques and OCT-defined
      vulnerable plaques (TCFAs). Former smokers have increased number of calcified
      plaques. These results may explain the increased risk of acute cardiac events
      among smokers. 

PMID- 25048345
TI  - Usefulness of the electrocardiogram in predicting cardiovascular mortality in
      asymptomatic adults with aortic stenosis (from the Simvastatin and Ezetimibe in
      Aortic Stenosis Study).
AB  - Hypertension and coronary heart disease are common in aortic stenosis (AS) and
      may impair prognosis for similar AS severity. Different changes in the
      electrocardiogram may be reflective of the separate impacts of AS, hypertension,
      and coronary heart disease, which could lead to enhanced risk stratification in
      AS. The aim of this study was therefore to examine if combining prognostically
      relevant electrocardiographic (ECG) findings improves prediction of
      cardiovascular mortality in asymptomatic AS. All patients with baseline
      electrocardiograms in the SEAS study were included. The primary end point was
      cardiovascular death. Backward elimination (p >0.01) identified heart rate, Q
      waves, and Cornell voltage-duration product as independently associated with
      cardiovascular death. Multivariate logistic and Cox regression models were used
      to evaluate if these 3 ECG variables improved prediction of cardiovascular death.
      In 1,473 patients followed for a mean of 4.3 years (6,362 patient-years of follow
      up), 70 cardiovascular deaths (5%) occurred. In multivariate analysis, heart rate
      (hazard ratio [HR] 1.5 per 11.2 minute(-1) [1 SD], 95% confidence interval [CI]
      1.2 to 1.8), sum of Q-wave amplitude (HR 1.3 per 2.0 mm [1 SD], 95% CI 1.1 to
      1.6), and Cornell voltage-duration product (HR 1.4 per 763 mm * ms [1 SD], 95% CI
      1.2 to 1.7) remained independently associated with cardiovascular death.
      Combining the prognostic information contained in each of the 3 ECG variables
      improved integrated discrimination for prediction of cardiovascular death by
      2.5%, net reclassification by 14.3%, and area under the curve by 0.06 (all p
      <=0.04) beyond other important risk factors. ECG findings add incremental
      predictive information for cardiovascular mortality in asymptomatic patients with
      AS. 

PMID- 25048346
TI  - Current state of mTOR targeting in human breast cancer.
AB  - BACKGROUND/AIM: The mammalian, or mechanistic, target of rapamycin (mTOR) pathway
      has been implicated in several models of human oncogenesis. Research in the role
      of mTOR in human oncogenesis remains a field of intense activity. In this mini
      review, we intend to recount our current understanding of the mTOR pathway, its
      interactions, and its role in human carcinogenesis in general, and breast cancer
      in particular. MATERIALS AND METHODS: We herein outline the discrete components
      of the two complexes of mTOR, and attempt to define their distinct roles and
      interactions. Furthermore, we review current developments in the therapeutic
      targeting of mTOR in human breast cancer. RESULTS: Our understanding of the
      organisation and interactions of the mTOR pathway continues to evolve. There has
      been significant incremental, albeit slow, progress in the therapeutic targeting
      of the mTOR pathway in human breast cancer. CONCLUSION: Continued progress in the
      field would require a better understanding of the role of the mTOR pathway in
      human breast cancer. By summarizing the current literature, this review will
      provide useful information on the topic.

PMID- 25048347
TI  - The metastasis suppressor NME1 regulates expression of genes linked to metastasis
      and patient outcome in melanoma and breast carcinoma.
AB  - NME1 is a well-documented metastasis suppressor gene, with suppressor activity
      demonstrated across a wide spectrum of human cancers including melanoma and
      carcinomas of the breast, stomach and thyroid. A primary aim of the current study
      was to identify profiles of genes whose expression is regulated by NME1 in cell
      lines of melanoma and thyroid carcinoma origin. Impact of NME1 was determined by
      forcing its expression transiently in cell lines using a novel Ad5-based
      adenoviral vector (Ad5-NME1), followed 48 h later by analysis of RNA expression
      profiles using the U133A microarray chip. Robust NME1 expression was achieved
      following infection with the Ad5-NME1 adenovirus in the human metastasis-derived
      cell lines WM1158 (melanoma) and WRO82 (follicular thyroid carcinoma), resulting
      in wide-ranging effects on gene expression in both settings. A substantial
      proportion of the NME1-regulated genes identified in the analyses were of clear
      potential relevance to metastasis, such as matrix metalloproteinase-1 (MMP1),
      angiopoietin-2 (ANGPT2), SERPINB9 and colony stimulating factor receptor-2B
      (CSFR2B). Nine genes were identified (false discovery rate <0.1) that were
      regulated by NME1 in both the WM1158 and WRO82 cell lines, each possessing one or
      more such metastasis-relevant activities as stress fiber formation and focal
      adhesion (PPM1E, ZYX, PFN1), chemotaxis (CCR1) epithelial-mesenchymal signaling
      (WNT6), differentiation and morphogenesis (TBX4, ZFP36L2), and G protein
      modulation (GPR52 and PFN1). In addition, a number of the NME1-regulated genes
      were shown to be of prognostic value for distant disease-free survival and
      overall survival in melanoma and breast cancer. The combined expression of three
      NME1-regulated genes CSFR2B, MSF4A1 and SERPINB9 provided a strongly synergistic
      correlation with distant disease-free survival in the basal subtype of breast
      cancer (p<3.5e(-5), hazard ratio=0.33). Our study demonstrates that analysis of
      NME1-dependent gene expression is a powerful approach for identifying potential
      modulators of metastatic potential in multiple cancer types, which in turn may
      represent useful therapeutic targets. The study also highlights NME1-dependent
      genes as potential prognostic/diagnostic indices, which are profoundly lacking at
      present in melanoma. 

PMID- 25048348
TI  - Comparative proteomic analysis reveals growth inhibition by 3-N-alkyloxyestradiol
      derivative (SERM) in prostate cancer cells.
AB  - BACKGROUND/AIM: In this study we evaluated the proteomic profile of PC-3 cells
      treated with novel, 3-N-alkyloxyestradiol derivative, 3-[2-diisopropylamino]
      ethoxy-D1,3,5 (10)-estrien-17-one (DI) (USPTO #7,687,486). MATERIALS AND METHODS:
      The growth inhibitory potential of DI was determined by the National Cancer
      Institute (NCI) Developmental Therapeutics Program. 2-D gel electrophoresis and
      mass spectrometry were employed to identify differentially expressed proteins
      after treatment with DI. RESULTS: Growth inhibitory (GI(50)) results showed that
      DI inhibited the growth of PC-3 and DU-145 cells, at 13.9 MUM and 30.8 MUM,
      respectively. Out of the proteins differentially expressed, five were selected
      for identification with four of those being successfully identified. The
      identified proteins play a role in protein folding, cell motility, carbohydrate
      biosynthesis, and carbohydrate degradation. CONCLUSION: Our studies resulted in
      the identification of targets associated with the glycolytic pathway and cell
      motility which have been implicated in the development and progression of many
      cancers.

PMID- 25048349
TI  - Open reading frames associated with cancer in the dark matter of the human
      genome.
AB  - BACKGROUND: The uncharacterized proteins (open reading frames, ORFs) in the human
      genome offer an opportunity to discover novel targets for cancer. A systematic
      analysis of the dark matter of the human proteome for druggability and biomarker
      discovery is crucial to mining the genome. Numerous data mining tools are
      available to mine these ORFs to develop a comprehensive knowledge base for future
      target discovery and validation. MATERIALS AND METHODS: Using the Genetic
      Association Database, the ORFs of the human dark matter proteome were screened
      for evidence of association with neoplasms. The Phenome-Genome Integrator tool
      was used to establish phenotypic association with disease traits including
      cancer. Batch analysis of the tools for protein expression analysis, gene
      ontology and motifs and domains was used to characterize the ORFs. RESULTS: Sixty
      two ORFs were identified for neoplasm association. The expression Quantitative
      Trait Loci (eQTL) analysis identified thirteen ORFs related to cancer traits.
      Protein expression, motifs and domain analysis and genome-wide association
      studies verified the relevance of these OncoORFs in diverse tumors. The OncoORFs
      are also associated with a wide variety of human diseases and disorders.
      CONCLUSIONS: Our results link the OncoORFs to diverse diseases and disorders.
      This suggests a complex landscape of the uncharacterized proteome in human
      diseases. These results open the dark matter of the proteome to novel cancer
      target research.

PMID- 25048351
TI  - Relational machine learning for electronic health record-driven phenotyping.
AB  - OBJECTIVE: Electronic health records (EHR) offer medical and pharmacogenomics
      research unprecedented opportunities to identify and classify patients at risk.
      EHRs are collections of highly inter-dependent records that include biological,
      anatomical, physiological, and behavioral observations. They comprise a patient's
      clinical phenome, where each patient has thousands of date-stamped records
      distributed across many relational tables. Development of EHR computer-based
      phenotyping algorithms require time and medical insight from clinical experts,
      who most often can only review a small patient subset representative of the total
      EHR records, to identify phenotype features. In this research we evaluate whether
      relational machine learning (ML) using inductive logic programming (ILP) can
      contribute to addressing these issues as a viable approach for EHR-based
      phenotyping. METHODS: Two relational learning ILP approaches and three well-known
      WEKA (Waikato Environment for Knowledge Analysis) implementations of non
      relational approaches (PART, J48, and JRIP) were used to develop models for nine
      phenotypes. International Classification of Diseases, Ninth Revision (ICD-9)
      coded EHR data were used to select training cohorts for the development of each
      phenotypic model. Accuracy, precision, recall, F-Measure, and Area Under the
      Receiver Operating Characteristic (AUROC) curve statistics were measured for each
      phenotypic model based on independent manually verified test cohorts. A two-sided
      binomial distribution test (sign test) compared the five ML approaches across
      phenotypes for statistical significance. RESULTS: We developed an approach to
      automatically label training examples using ICD-9 diagnosis codes for the ML
      approaches being evaluated. Nine phenotypic models for each ML approach were
      evaluated, resulting in better overall model performance in AUROC using ILP when
      compared to PART (p=0.039), J48 (p=0.003) and JRIP (p=0.003). DISCUSSION: ILP has
      the potential to improve phenotyping by independently delivering clinically
      expert interpretable rules for phenotype definitions, or intuitive phenotypes to
      assist experts. CONCLUSION: Relational learning using ILP offers a viable
      approach to EHR-driven phenotyping.

PMID- 25048352
TI  - A smartphone-driven methodology for estimating physical activities and energy
      expenditure in free living conditions.
AB  - This paper introduces a function dedicated to the estimation of total energy
      expenditure (TEE) of daily activities based on data from accelerometers
      integrated into smartphones. The use of mass-market sensors such as
      accelerometers offers a promising solution for the general public due to the
      growing smartphone market over the last decade. The TEE estimation function
      quality was evaluated using data from intensive numerical experiments based,
      first, on 12 volunteers equipped with a smartphone and two research sensors
      (Armband and Actiheart) in controlled conditions (CC) and, then, on 30 other
      volunteers in free-living conditions (FLC). The TEE given by these two sensors in
      both conditions and estimated from the metabolic equivalent tasks (MET) in CC
      served as references during the creation and evaluation of the function. The TEE
      mean gap in absolute value between the function and the three references was
      7.0%, 16.4% and 2.7% in CC, and 17.0% and 23.7% according to Armband and
      Actiheart, respectively, in FLC. This is the first step in the definition of a
      new feedback mechanism that promotes self-management and daily-efficiency
      evaluation of physical activity as part of an information system dedicated to the
      prevention of chronic diseases. 

PMID- 25048353
TI  - The effect of mother's age and other related factors on neonatal survival
      associated with first and second birth in rural, Tanzania: evidence from Ifakara
      health and demographic surveillance system in rural Tanzania.
AB  - BACKGROUND: With a view to improve neonatal survival, data on birth outcomes are
      critical for planning maternal and child health care services. We present
      information on neonatal survival from Ifakara Health and Demographic Surveillance
      System (HDSS) in Tanzania, regarding the influence of mother's age and other
      related factors on neonatal survival of first and second births. METHODS: The
      study conducted analysis using longitudinal health and demographic data collected
      from Ifakara HDSS in parts of Kilombero and Ulanga districts in Morogoro region.
      The analysis included first and second live births that occurred within six years
      (2004-2009) and the unit of observation was a live birth. A logistic regression
      model was used to assess the influence of socio-demographic factors on neonates'
      survival. RESULTS: A total of 18,139 first and second live births were analyzed.
      We found neonatal mortality rate of 32 per 1000 live births (95% CI: 29/1000
      34/1000). Results from logistic regression model indicated increase in risk of
      neonatal mortality among neonates those born to young mothers aged 13-19 years
      compared with those whose mother's aged 20-34 years (aOR = 1.64, 95% CI = 1.34
      2.02). We also found that neonates in second birth order were more likely to die
      than those in first birth order (aOR = 1.85: 95% CI = 1.52-2.26). The risk of
      neonatal mortality among offspring of women who had a partner co-resident was 18%
      times lower as compared with offspring of mothers without a partner co-resident
      in the household (aOR = 0.82: 95% CI = 0.66-0.98). Short birth interval (<33
      months) was associated with increased risk of neonatal mortality (aOR = 1.50, 95%
      CI =1.16-1.96) compared with long birth interval (> = 33 months). Male born
      neonates were found to have an increased risk (aOR = 1.34, 95% CI =1.13- 1.58) of
      neonatal mortality as compared to their female counterparts. CONCLUSIONS:
      Delaying the age at first birth may be a valuable strategy to promote and improve
      neonatal health and survival. Moreover, birth order, birth interval, mother's
      partner co-residence and sex of the neonate appeared as important markers for
      neonatal survival.

PMID- 25048354
TI  - Prevalence, determinants and patterns of multimorbidity in primary care: a
      systematic review of observational studies.
AB  - INTRODUCTION: Multimorbidity is a major concern in primary care. Nevertheless,
      evidence of prevalence and patterns of multimorbidity, and their determinants,
      are scarce. The aim of this study is to systematically review studies of the
      prevalence, patterns and determinants of multimorbidity in primary care. METHODS:
      Systematic review of literature published between 1961 and 2013 and indexed in
      Ovid (CINAHL, PsychINFO, Medline and Embase) and Web of Knowledge. Studies were
      selected according to eligibility criteria of addressing prevalence,
      determinants, and patterns of multimorbidity and using a pretested proforma in
      primary care. The quality and risk of bias were assessed using STROBE criteria.
      Two researchers assessed the eligibility of studies for inclusion (Kappa= 0.86).
      RESULTS: We identified 39 eligible publications describing studies that included
      a total of 70,057,611 patients in 12 countries. The number of health conditions
      analysed per study ranged from 5 to 335, with multimorbidity prevalence ranging
      from 12.9% to 95.1%. All studies observed a significant positive association
      between multimorbidity and age (odds ratio [OR], 1.26 to 227.46), and lower
      socioeconomic status (OR, 1.20 to 1.91). Positive associations with female gender
      and mental disorders were also observed. The most frequent patterns of
      multimorbidity included osteoarthritis together with cardiovascular and/or
      metabolic conditions. CONCLUSIONS: Well-established determinants of
      multimorbidity include age, lower socioeconomic status and gender. The most
      prevalent conditions shape the patterns of multimorbidity. However, the
      limitations of the current evidence base means that further and better designed
      studies are needed to inform policy, research and clinical practice, with the
      goal of improving health-related quality of life for patients with
      multimorbidity. Standardization of the definition and assessment of
      multimorbidity is essential in order to better understand this phenomenon, and is
      a necessary immediate step.

PMID- 25048355
TI  - Predictive factors for survival and recurrence rate in patients with node
      negative gastric cancer--a European single-centre experience.
AB  - PURPOSE: Gastric cancer is a common disease with poor prognosis. Lymph node
      involvement is the strongest prognostic factor regarding survival in curatively
      (R0) resected patients. The aim of this study was to determine if a subgroup with
      higher risk for tumour recurrence exists in patients with node-negative gastric
      cancer. Furthermore, we aimed to identify prognostic factors and recurrence
      patterns for this subgroup. METHODS: We collected demographical, clinical,
      pathohistological and follow-up data from 1,074 patients with gastric cancer in a
      prospectively maintained database. In 228 cases, R0 resections for node-negative
      gastric cancer were performed. The median follow-up period was 59 months.
      Statistical analysis was performed using SPSS 19.0. RESULTS: The 5- , 10- and 15
      year overall survival was 83, 75.5 and 73 %, respectively, with a disease-free
      survival of 78, 73 and 73 %. Tumour recurrence was observed in 18.9 % (43 cases),
      14 % of which were diagnosed after more than 5 years. Gender, T-category ,
      lymphangioinvasion, tumour differentiation, serosal infiltration, histological
      growth pattern, tumour size and classification according to Lauren were
      significant prognostic factors for overall survival in univariate analysis.
      Multivariate analysis showed tumour size and female sex to be independent
      prognostic factors. Non-exophytic tumour growth was a relevant factor for the
      development of local recurrence. Diffuse type gastric cancers as well as signet
      ring cells were significantly associated with the development of peritoneal
      carcinomatosis, and male gender with hematogenous metastases. CONCLUSIONS:
      Multimodal treatment and individual follow-up might be beneficial in patients
      with higher risk of recurrence after R0 resection of node-negative gastric
      cancer.

PMID- 25048356
TI  - The negligible effects of the antifungal natamycin on cholesterol-dipalmitoyl
      phosphatidylcholine monolayers may explain its low oral and topical toxicity for
      mammals.
AB  - Natamycin is an effective, broad spectrum antifungal with no reported resistance,
      in contrast to most antimicrobials. It also exhibits reduced (oral and topical)
      toxicity to humans, which is probably associated with the lack of effects on
      mammalian cell membranes. In this paper we employ Langmuir monolayers to mimic a
      cell membrane, whose properties are interrogated with various techniques. We
      found that natamycin has negligible effects on Langmuir monolayers of dipalmitoyl
      phosphatidylcholine (DPPC), but it strongly affects cholesterol monolayers.
      Natamycin causes the surface pressure isotherm of a cholesterol monolayer to
      expand even at high surface pressures since it penetrates into the hydrophobic
      chains. It also reduces the compressibility modulus, probably because natamycin
      disturbs the organization of the cholesterol molecules, as inferred with
      polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). In
      mixed cholesterol/DPPC monolayers, strong effects from natamycin were only
      observed when the cholesterol concentration was 50mol% or higher, well above its
      concentration in a mammalian cell membrane. For a sterol concentration that
      mimics a real cell membrane in mammals, i.e. with 25mol% of cholesterol, the
      effects were negligible, which may explain why natamycin has low toxicity when
      ingested and/or employed to treat superficial fungal infections. 

PMID- 25048357
TI  - Synthesis, characterization and toxicological evaluation of iron oxide
      nanoparticles in human lung alveolar epithelial cells.
AB  - The present investigation was aimed to characterize the synthesized iron oxide
      nanoparticles (Fe3O4-NPs) and to assess their cytotoxicity and oxidative stress
      in human lung alveolar epithelial cells (A-549). Fe3O4-NPs were characterized by
      X-ray diffraction, transmission electron microscopy, dynamic light scattering,
      and atomic force microscopy. The morphology of the Fe3O4-NPs was found to be
      variable with a size range of 36nm. A-549 cells were exposed to Fe3O4-NPs (10
      50MUg/ml concentrations) for 24h. Post exposure, cytotoxicity assays (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT; neutral red uptake,
      NRU; and cellular morphology) and oxidative stress (lipid peroxidation, LPO and
      glutathione, GSH) were evaluated. Further, intracellular reactive oxygen species
      (ROS) generation and mitochondrial membrane potential (MMP) were also studied.
      MTT and NRU assays revealed a concentration-dependent decrease in the cell
      viability of A-549 cells. Fe3O4-NPs exposed cells also altered the normal
      morphology of the cells. Furthermore, the cells showed significant induction of
      oxidative stress. This was confirmed by the increase in LPO and ROS generation,
      and the decrease in the GSH level and MMP. Our results demonstrated that Fe3O4
      NPs induced cytotoxicity is likely to be mediated through the oxidative stress
      and ROS generation in A-549 cells. 

PMID- 25048358
TI  - Correlation between surface physicochemical properties and the release of iron
      from stainless steel AISI 304 in biological media.
AB  - Stainless steel is widely used in biological environments, for example as implant
      material or in food applications, where adsorption-controlled ligand-induced
      metal release is of importance from a corrosion, health, and food safety
      perspective. The objective of this study was to elucidate potential correlations
      between surface energy and wettability of stainless steel surfaces and the
      release of iron in complexing biological media. This was accomplished by studying
      changes in surface energies calculated from contact angle measurements, surface
      oxide composition (X-ray photoelectron spectroscopy), and released iron (graphite
      furnace atomic absorption spectroscopy) for stainless steel grade AISI 304
      immersed in fluids containing bovine serum albumin or citric acid, and non
      complexing fluids such as NaCl, NaOH, and HNO3. It was shown that the surface
      wettability and polar surface energy components were all influenced by
      adventitious atmospheric carbon (surface contamination of low molecular weight),
      rather than differences in surface oxide composition in non-complexing solutions.
      Adsorption of both BSA and citrate, which resulted in ligand-induced metal
      release, strongly influenced the wettability and the surface energy, and
      correlated well with the measured released amount of iron. 

PMID- 25048359
TI  - Crosslinked triblock copolymeric micelle for redox-responsive drug delivery.
AB  - In this paper, novel biodegradable amphiphilic triblock copolymer based on
      methoxy poly(ethylene glycol)-b-poly(E-caprolactone)-b-poly(2-(2-oxo-1,3,2
      dioxaphospholoyloxy)ethyl methacrylate) (mPEG-b-PCL-b-PPEMA) was successfully
      synthesized. After Michael-addition reactions between amine groups of cystamine
      and carbon-carbon double bonds of PPEMA segments, the crosslinked reduction
      sensitive copolymer mPEG-b-PCL-b-PPEMA-SS- was obtained for efficient delivery
      and controlled release of doxorubicin (DOX) to cancer cells. Both the
      uncrosslinked and crosslinked copolymers could self-assemble to form nano-sized
      micelles in aqueous solution, while transmission electron microscopy (TEM)
      observation showed that the micelles dispersed in spherical shape with nano-size
      before and after DOX loading. Meanwhile, (1)H NMR spectra in D2O indicated the
      formation of a lower mobility core by crosslinking method and a solid-like rigid
      core via further DOX-loaded. As compared to the uncrosslinked copolymer, the core
      crosslinking structure in mPEG-b-PCL-b-PPEMA-SS- could improve the micellar
      stability and enhance the drug loading capacity and entrapment efficiency. The in
      vitro release studies showed more sustained drug release behavior of crosslinked
      mPEG-b-PCL-b-PPEMA-SS- which could be accelerated quantitatively in response to
      the reductive condition similar to intracellular environment. Furthermore,
      confocal laser scanning microscopy (CLSM) indicated much more efficient cellular
      uptake of DOX delivered by mPEG-b-PCL-b-PPEMA-SS-, while MTT assays also
      demonstrated potent cytotoxic activity against HeLa cells. 

PMID- 25048360
TI  - On the correlation between the structure of lyotropic carriers and the delivery
      profiles of two common NSAIDs.
AB  - Two non-steroidal anti-inflammatory drugs (NSAIDs), sodium diclofenac (Na-DFC)
      and celecoxib (CLXB) were solubilized within cubic and lamellar mesophases as
      carriers for transdermal drug delivery. SD-NMR, SAXS, ATR-FTIR, and EPR
      measurements were performed to examine the systems' characteristics and the
      interactions between the drugs and their hosting mesophases. The amphiphilic drug
      Na-DFC was found to incorporate at the interfaces of the cubic and lamellar
      mesophases and thus to act as a cosurfactant and a "structure stabilizer". It
      increased the order degree and the interactions between the GMO molecules and led
      the systems toward denser packing. CLXB exhibits an opposite effect on the
      mesophases. Its solubilization within both systems is accompanied with
      significant channel swelling and decrease in the order degree. The hydrophobic,
      rigid and bulky CLXB behaves as a "structure breaker", incorporated between the
      GMO tails, disturbing the mesophase packing and enhancing the repulsion at the
      tails region, limiting their close binding. Release experiments from Franz cells
      revealed that Na-DFC release is dependent on the quantity of water within the
      hosting mesophase as the water-rich formulation exhibits 1.5-fold enhancement in
      the release of the drug, compared to the lamellar phase. In contrast, CLXB
      release was not influenced by the water quantity, hinting that the release
      mechanisms of the drugs are different while Na-DFC diffuses from the water
      channels to the external phase, CLXB diffusion occurs through the continuous
      lipophilic region. The difference in the solubilization sites and interactions of
      each drug with the mesophases affect their release profiles and determine the
      preferred formulations for each drug's delivery vehicle. 

PMID- 25048362
TI  - Methyl gallate from Galla rhois successfully controls clinical isolates of
      Salmonella infection in both in vitro and in vivo systems.
AB  - Galla rhois is a commonly used traditional medicine for the treatment of
      pathogenic bacteria in Korea as well as in other parts of Asia. Methyl gallate
      (MG), a major component of Galla Rhois, exhibits strong antibacterial activity,
      but its mechanism of action against Salmonella spp. is unclear. In the present
      study, we investigated the antibacterial actions of MG against Salmonella. The
      antibacterial activity determined by broth dilution method indicated that the
      antibacterial activity of MG against Salmonella strains ranged from 3.9 to 125
      ug/ml. In vitro bacterial viability test indicated that MG significantly
      decreased the viability of Salmonella over 40% when combined with ATPase
      inhibitors. The time-kill curves showed that a combined MG and ATPase inhibitors
      (DCCD and NaN3) treatment reduced the bacterial counts dramatically after 24 h.
      Oral administration of MG showed a strong anti-bacterial activity against WS-5
      infected BALB/c mice. In contrast to the untreated Salmonella infected control
      animals, MG treated groups showed no clinical symptoms of the disease, such as
      lethargy and liver damage. It was observed that MG treatment significantly
      increased the survival of animals from Salmonella infection, while in untreated
      groups all animal succumbed to disease by the sixth day post infection. Thus, the
      present study demonstrates the therapeutic ability of MG against Salmonella
      infections. 

PMID- 25048363
TI  - Mapping of the outcome measures in rheumatology core set for antineutrophil
      cytoplasmic antibody-associated vasculitis to the International Classification of
      Function, Disability and Health.
AB  - OBJECTIVE: The International Classification of Functioning, Disability and Health
      (ICF) is a framework and classification of health that describes health along 4
      components: body functions, body structures, activities and participation, and
      contextual factors. This study examined the content of instruments that
      constitute the Outcome Measures in Rheumatology (OMERACT) core set of outcome
      measures for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) by
      "mapping" them to the ICF. METHODS: The content of the instruments included in
      the AAV core set were linked to the ICF by 2 independent investigators according
      to previously established ICF linkage rules. RESULTS: The AAV core set includes 3
      measures of disease activity (3 versions of the Birmingham Vasculitis Activity
      Score), 1 damage measure (Vasculitis Damage Index), 1 patient-reported outcome
      (Short Form 36 health survey), and death. Linking these instruments to the ICF
      revealed comprehensive coverage of the ICF components body functions and body
      structures, limited coverage of the ICF component activities and participation,
      and complete absence of coverage of contextual factors. CONCLUSION: ICF was found
      to be useful for thematic characterization of a heterogeneous group of outcome
      measures for AAV, i.e., a group of complex medical conditions. Linking of the
      instruments selected for the OMERACT AAV core set of outcome measures to the ICF
      classification revealed limitations in the representation of constructs related
      to life impact of AAV, represented by the ICF components activities and
      participation and contextual factors. Further research and methods development
      are needed to better incorporate important aspects of functioning and health
      relevant to patients into clinical trials of AAV.

PMID- 25048365
TI  - The Paediatric migraine disability assessment score is a useful tool for
      evaluating prophylactic migraine treatment.
AB  - AIM: There is a need for an objective assessment scoring system to evaluate the
      effectiveness of prophylactic drugs in paediatric migraine, and the aim of this
      study was to evaluate the Paediatric Migraine Disability Assessment Score
      (PedMIDAS). METHODS: We recruited 88 children aged between 6 and 17 years of age
      with migraine. The 53 children in the treatment group were divided into three
      groups according to the prophylactic drug they received topiramate, flunarizine
      and propranolol and assessed using PedMIDAS before the start of treatment and 3
      and 6 months after treatment. The 35 patients in the control group did not
      receive prophylactic treatment and were assessed with PedMIDAS on three
      occasions, 3 months apart. RESULTS: Topiramate, propranolol and flunarizine
      treatments significantly decreased PedMIDASs and were shown to be effective in
      improving the patients' quality of life. Topiramate and propranolol were more
      effective than flunarizine. The number of days on analgesic treatment
      significantly decreased in the patients who had received topiramate and
      propranolol treatments (p < 0.05), but remained unchanged in the flunarizine
      prophylaxis group (p > 0.05). CONCLUSION: The PedMIDAS scoring system is useful
      in evaluating the efficacy of prophylactic therapy in paediatric migraine.
      Topiramate and propranolol lowered the PedMIDASs better than flunarizine.

PMID- 25048366
TI  - Combination therapy with ruxolitinib plus 5-azacytidine or continuous infusion of
      low dose cytarabine is feasible in patients with blast-phase myeloproliferative
      neoplasms.

PMID- 25048361
TI  - Association of cancer metabolism-related proteins with oral carcinogenesis -
      indications for chemoprevention and metabolic sensitizing of oral squamous cell
      carcinoma?
AB  - BACKGROUND: Tumor metabolism is a crucial factor for the carcinogenesis of oral
      squamous cell carcinoma (OSCC). METHODS: Expression of IGF-R1, glycolysis-related
      proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB,
      ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions
      (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n =
      35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase
      chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins
      were correlated with proliferation activity (Ki-67) and apoptotic properties
      (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western
      blotting in cancer cell lines. RESULTS: Expression of IGF-R1, glycolysis-related
      proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP
      synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic
      active regions of OSCC were strongly correlated with proliferating cancer (Ki
      67+) cells without detection of apoptosis (TUNEL assay). CONCLUSIONS: This study
      provides the first evidence of the expression of IGF-R1, glycolysis-related
      proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes
      SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both,
      hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation
      characteristics are associated with the carcinogenesis of OSCC. Acidosis and
      OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP).
      Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial
      therapies (ROS generation) by natural compounds or synthetic vitamin derivatives
      may act as sensitizer for apoptosis in cancer cells mediated by adjuvant
      therapies in OSCC.

PMID- 25048368
TI  - Vitamin D deficiency aggravates nephrotoxicity, hypertension and dyslipidemia
      caused by tenofovir: role of oxidative stress and renin-angiotensin system.
AB  - Vitamin D deficiency (VDD) is prevalent among HIV-infected individuals. Vitamin D
      has been associated with renal and cardiovascular diseases because of its effects
      on oxidative stress, lipid metabolism and renin-angiotensin-aldosterone system
      (RAAS). Tenofovir disoproxil fumarate (TDF), a widely used component of
      antiretroviral regimens for HIV treatment, can induce renal injury. The aim of
      this study was to investigate the effects of VDD on TDF-induced nephrotoxicity.
      Wistar rats were divided into four groups: control, receiving a standard diet for
      60 days; VDD, receiving a vitamin D-free diet for 60 days; TDF, receiving a
      standard diet for 60 days with the addition of TDF (50 mg/kg food) for the last
      30 days; and VDD+TDF receiving a vitamin D-free diet for 60 days with the
      addition of TDF for the last 30 days. TDF led to impaired renal function,
      hyperphosphaturia, hypophosphatemia, hypertension and increased renal vascular
      resistance due to downregulation of the sodium-phosphorus cotransporter and
      upregulation of angiotensin II and AT1 receptor. TDF also increased oxidative
      stress, as evidenced by higher TBARS and lower GSH levels, and induced
      dyslipidemia. Association of TDF and VDD aggravated renovascular effects and TDF
      induced nephrotoxicity due to changes in the redox state and involvement of RAAS.

PMID- 25048369
TI  - The use of fosmid metagenomic libraries in preliminary screening for various
      biological activities.
AB  - BACKGROUND: It is generally believed that there are many natural sources of as
      yet unknown bioactive compounds with a high biotechnological potential. However,
      the common method based on the use of cell extracts in the preliminary screening
      for particular molecules or activities is problematic as amounts of obtained
      compounds may be low, and such experiments are hardly reproducible. Therefore,
      the aim of this work was to test whether a novel strategy to search for
      previously unknown biological activities can be efficient. This strategy is based
      on construction of metagenomic libraries and employment of Escherichia coli
      strains as cell factories producing compounds of properties potentially useful in
      biotechnology. RESULTS: Three cyanobacterial metagenomic libraries were
      constructed in the fosmid system. The libraries were screened for various
      biological activities. Extracts from selected E. coli clones bearing constructs
      with fragments of cyanobacterial genomes revealed antimicrobial or anticancer
      activities. Interestingly, stimulation of growth of host bacteria bearing
      particular plasmids with certain cyanobacterial genes was detected, suggesting a
      potential possibility for improvement of E. coli cultivation during
      biotechnological production. The most interesting plasmids were sequenced, and
      putative mechanisms of biological effects caused by cyanobacterial gene products
      are discussed. CONCLUSIONS: The strategy of exploring cyanobacteria as sources of
      bioactive compounds, based on E. coli cell factories producing compounds due to
      expression of genes from metagenomic libraries, appears to be effective.

PMID- 25048370
TI  - Subconjunctival Versus Intrascleral Application Of Mitomycin C During
      Trabeculectomy.
AB  - Purpose: To compare efficacy and safety between subconjunctival and intrascleral
      methods of mitomycin C (MMC) application during trabeculectomy Methods: This
      retrospective study included 165 eyes treated by trabeculectomy and compared
      clinical outcomes between eyes that received subconjunctival MMC (Group 1, 80
      eyes, 48.5%) and eyes that received intrascleral (Group 2, 85 eyes, 51.5%) MMC.
      Surgical success was defined as an intraocular pressure (IOP) of 6-21 mmHg with
      or without topical antiglaucoma medication use. Results: Mean IOP values were not
      significantly different between Group 1 and Group 2 (P > 0.05) until 2 weeks
      after surgery, while they differed significantly at 1, 3, 6, 12, and 24 months
      after surgery (P < 0.05). The mean number of antiglaucoma medications was 3.6 +/-
      0.6 and 3.5 +/- 0.7, respectively, before surgery (P = 0.327) and 0.27 +/- 0.32
      and 0.10 +/- 0.29, respectively, at 24 months after surgery (P = 0.001). The
      surgical success rate at 24 months was 86.25% and 94.12% in Groups 1 and 2,
      respectively (P = 0.041; log-rank test). Encysted blebs were observed in 17 and 8
      patients in Groups 1 and 2 (P = 0.034), respectively, at 24 months. There was no
      statistically significant difference in the incidence of hypotony, choroidal
      detachment, conjunctival leakage, cataract and the rate of postoperative
      procedures between Groups 1 and 2 (P > 0.05). Conclusions: Compared to the
      subconjunctival method, the intrascleral method of MMC application can increase
      the long-term success of trabeculectomy without increasing the complication rate.

PMID- 25048371
TI  - Pre-anaphase chromosome oscillations are regulated by the antagonistic activities
      of Cdk1 and PP1 on Kif18A.
AB  - Upon congression at the spindle equator, vertebrate chromosomes display
      oscillatory movements which typically decline as cells progress towards anaphase.
      Kinesin-8 Kif18A has been identified as a suppressor of chromosome movements, but
      how its activity is temporally regulated to dampen chromosome oscillations before
      anaphase onset remained mysterious. Here, we identify a regulatory network
      composed of cyclin-dependent kinase-1 (Cdk1) and protein phosphatase-1 (PP1) that
      antagonistically regulate Kif18A. Cdk1-mediated inhibitory phosphorylation of
      Kif18A promotes chromosome oscillations in early metaphase. PP1 induces metaphase
      plate thinning by directly dephosphorylating Kif18A. Chromosome attachment
      induces Cdk1 inactivation and kinetochore recruitment of PP1alpha/gamma. Thus, we
      propose that chromosome biorientation mediates the alignment of chromosomes at
      the metaphase plate by tipping the balance in favour of dephosphorylated Kif18A
      capable of suppressing the oscillatory movements of chromosomes. Notably,
      interfering with chromosome oscillations severely impairs the fidelity of sister
      chromatid segregation demonstrating the importance of timely controlled
      chromosome dynamics for the maintenance of genome integrity. 

PMID- 25048372
TI  - Lyme disease risk influences human settlement in the wildland-urban interface:
      evidence from a longitudinal analysis of counties in the northeastern United
      States.
AB  - The expansion of human settlement into wildland areas, including forests in the
      eastern United States, has resulted in fragmented forest habitat that has been
      shown to drive higher entomological risk for Lyme disease. We investigated an
      alternative pathway between fragmentation and Lyme disease, namely whether
      increased risk of Lyme disease results in a reduced propensity to settle in high
      risk areas at the interface of developed and undeveloped lands. We used
      longitudinal data analyses at the county level to determine whether Lyme disease
      incidence (LDI) influences the proportion of the population residing in the
      wildland-urban interface in 12 high LDI states in the eastern United States. We
      found robust evidence that a higher LDI reduces the proportion of a county's
      population residing in the wildland-urban interface in high-LDI states. This
      study provides some of the first evidence of human behavioral responses to Lyme
      disease risk via settlement decisions. 

PMID- 25048373
TI  - Identifying etiological agents causing diarrhea in low income Ecuadorian
      communities.
AB  - Continued success in decreasing diarrheal disease burden requires targeted
      interventions. To develop such interventions, it is crucial to understand which
      pathogens cause diarrhea. Using a case-control design we tested stool samples,
      collected in both rural and urban Ecuador, for 15 pathogenic microorganisms.
      Pathogens were present in 51% of case and 27% of control samples from the urban
      community, and 62% of case and 18% of control samples collected from the rural
      community. Rotavirus and Shigellae were associated with diarrhea in the urban
      community; co-infections were more pathogenic than single infection;
      Campylobacter and Entamoeba histolytica were found in large numbers in cases and
      controls; and non-typhi Salmonella and enteropathogenic Escherichia coli were not
      found in any samples. Consistent with the Global Enteric Multicenter Study,
      focused in south Asia and sub-Saharan Africa, we found that in Ecuador a small
      group of pathogens accounted for a significant amount of the diarrheal disease
      burden. 

PMID- 25048374
TI  - Asymptomatic intestinal amebiasis in Japanese HIV-1-infected individuals.
AB  - Seventy-one asymptomatic human immunodeficiency virus-1 (HIV-1) -infected
      individuals who underwent colonoscopy for detection of diseases other than
      amebiasis were included in this study. Ulcerative lesions caused by Entamoeba
      histolytica were identified by colonoscopy and biopsy in 11.3% (8 of 71) of
      individuals. Stool microscopic examination hardly identified Entamoeba, whereas
      serum antibody against E. histolytica was often elevated in patients with
      subclinical intestinal amebiasis. Human leukocyte antigen (HLA) class II allele
      against E. histolytica infection (DQB1*06:01) was frequently identified in these
      patients. This study emphasizes the endemic nature of E. histolytica infection in
      our cohort and the difficulties in epidemiological control. 

PMID- 25048376
TI  - Dropsy outbreak in a single family in Punjab, India.
AB  - Epidemic dropsy is caused by consumption of mustard oil contaminated with
      argemone oil. It usually occurs in outbreaks with acute manifestation of
      bilateral pitting edema, erythema, and local tenderness along with cardiac and
      respiratory problems in severe cases leading to death. We report an outbreak that
      is unusual because of its gradual onset, clustering in a single family, and with
      major manifestation of gastrointestinal illness mimicking acute gastroenteritis,
      hence leading to delayed diagnosis and high mortality. Thus, the diagnosis of
      epidemic dropsy should be considered as a strong possibility when there is
      clustering of cases in a single family with on and off gastrointestinal symptoms
      of vomiting and diarrhea in a mustard oil consuming belt. 

PMID- 25048377
TI  - PGMS: a case study of collecting PDA-based geo-tagged malaria-related survey
      data.
AB  - Using mobile devices, such as personal digital assistants (PDAs), smartphones,
      tablet computers, etc., to electronically collect malaria-related field data is
      the way for the field questionnaires in the future. This case study seeks to
      design a generic survey framework PDA-based geo-tagged malaria-related data
      collection tool (PGMS) that can be used not only for large-scale community-level
      geo-tagged electronic malaria-related surveys, but also for a wide variety of
      electronic data collections of other infectious diseases. The framework includes
      two parts: the database designed for subsequent cross-sectional data analysis and
      the customized programs for the six study sites (two in Kenya, three in
      Indonesia, and one in Tanzania). In addition to the framework development, we
      also present our methods used when configuring and deploying the PDAs to 1)
      reduce data entry errors, 2) conserve battery power, 3) field install the
      programs onto dozens of handheld devices, 4) translate electronic questionnaires
      into local languages, 5) prevent data loss, and 6) transfer data from PDAs to
      computers for future analysis and storage. Since 2008, PGMS has successfully
      accomplished quite a few surveys that recorded 10,871 compounds and households,
      52,126 persons, and 17,100 bed nets from the six sites. These numbers are still
      growing. 

PMID- 25048375
TI  - Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and
      multidrug resistance 1 genes: parasite risk factors that affect treatment
      outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate
      amodiaquine.
AB  - Adequate clinical and parasitologic cure by artemisinin combination therapies
      relies on the artemisinin component and the partner drug. Polymorphisms in the
      Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P.
      falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased
      sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms
      on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether
      lumefantrine (AL) have not been clearly defined. Individual patient data from 31
      clinical trials were harmonized and pooled by using standardized methods from the
      WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were
      analyzed to assess relationships between parasite polymorphisms in pfcrt and
      pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence
      of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval =
      2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio
      = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant
      independent risk factors for recrudescence in patients treated with AL. AL and
      ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in
      pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug
      resistance are critical tools for preserving efficacy of artemisinin combination
      therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y
      should now be routine. 

PMID- 25048378
TI  - Multichannel imaging to quantify four classes of pharmacokinetic distribution in
      tumors.
AB  - Low and heterogeneous delivery of drugs and imaging agents to tumors results in
      decreased efficacy and poor imaging results. Systemic delivery involves a complex
      interplay of drug properties and physiological factors, and heterogeneity in the
      tumor microenvironment makes predicting and overcoming these limitations
      exceptionally difficult. Theoretical models have indicated that there are four
      different classes of pharmacokinetic behavior in tissue, depending on the
      fundamental steps in distribution. In order to study these limiting behaviors, we
      used multichannel fluorescence microscopy and stitching of high-resolution images
      to examine the distribution of four agents in the same tumor microenvironment. A
      validated generic partial differential equation model with a graphical user
      interface was used to select fluorescent agents exhibiting these four classes of
      behavior, and the imaging results agreed with predictions. BODIPY-FL exhibited
      higher concentrations in tissue with high blood flow, cetuximab gave perivascular
      distribution limited by permeability, high plasma protein and target binding
      resulted in diffusion-limited distribution for Hoechst 33342, and Integrisense
      680 was limited by the number of binding sites in the tissue. Together, the
      probes and simulations can be used to investigate distribution in other tumor
      models, predict tumor drug distribution profiles, and design and interpret in
      vivo experiments.

PMID- 25048379
TI  - Predictors of eHealth usage: insights on the digital divide from the Health
      Information National Trends Survey 2012.
AB  - BACKGROUND: Recent eHealth developments have elevated the importance of assessing
      the extent to which technology has empowered patients and improved health,
      particularly among the most vulnerable populations. With noted disparities across
      racial and social groups in chronic health outcomes, such as cancer, obesity, and
      diabetes, it is essential that researchers examine any differences in the
      implementation, uptake, and impact of eHealth strategies across groups that bear
      a disproportionate burden of disease. OBJECTIVE: The goal was to examine eHealth
      use by sociodemographic factors, such as race/ethnicity, socioeconomic status
      (SES), age, and sex. METHODS: We drew data from National Cancer Institute's 2012
      Health Information National Trends Survey (HINTS) (N=3959) which is publicly
      available online. We estimated multivariable logistic regression models to assess
      sociodemographic predictors of eHealth use among adult Internet users (N=2358)
      across 3 health communication domains (health care, health information-seeking,
      and user-generated content/sharing). RESULTS: Among online adults, we saw no
      evidence of a digital use divide by race/ethnicity. However, there were
      significant differences in use by SES, particularly for health care and health
      information-seeking items. Patients with lower levels of education had
      significantly lower odds of going online to look for a health care provider (high
      school or less: OR 0.50, 95% CI 0.33-0.76) using email or the Internet to
      communicate with a doctor (high school or less: OR 0.46, 95% CI 0.29-0.72),
      tracking their personal health information online (high school or less: OR 0.53,
      95% CI 0.32-0.84), using a website to help track diet, weight, and physical
      activity (high school or less: OR 0.64, 95% CI 0.42-0.98; some college: OR 0.67,
      95% CI 0.49-0.93), or downloading health information to a mobile device (some
      college: OR 0.54, 95% CI 0.33-0.89). Being female was a consistent predictor of
      eHealth use across health care and user-generated content/sharing domains,
      whereas age was primarily influential for health information-seeking.
      CONCLUSIONS: This study illustrates that lower SES, older, and male online US
      adults were less likely to engage in a number of eHealth activities compared to
      their counterparts. Future studies should assess issues of health literacy and
      eHealth literacy and their influence on eHealth engagement across social groups.
      Clinical care and public health communication efforts attempting to leverage Web
      2.0 and 3.0 platforms should acknowledge differential eHealth usage to better
      address communication inequalities and persistent disparities in health.

PMID- 25048380
TI  - Does swimming exercise affect experimental chronic kidney disease in rats treated
      with gum acacia?
AB  - Different modes of exercise are reported to be beneficial in subjects with
      chronic kidney disease (CKD). Similar benefits have also been ascribed to the
      dietary supplement gum acacia (GA). Using several physiological, biochemical,
      immunological, and histopathological measurements, we assessed the effect of
      swimming exercise (SE) on adenine-induced CKD, and tested whether SE would
      influence the salutary action of GA in rats with CKD. Eight groups of rats were
      used, the first four of which were fed normal chow for 5 weeks, feed mixed with
      adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were
      given adenine plus GA, as above. Another four groups were similarly treated, but
      were subjected to SE during the experimental period, while the first four groups
      remained sedentary. The pre-SE program lasted for four days (before the start of
      the experimental treatments), during which the rats were made to swim for 5 to 10
      min, and then gradually extended to 20 min per day. Thereafter, the rats in the
      5th, 6th, 7th, and 8th groups started to receive their respective treatments, and
      were subjected to SE three days a week for 45 min each. Adenine induced the
      typical signs of CKD as confirmed by histopathology, and the other measurements,
      and GA significantly ameliorated all these signs. SE did not affect the salutary
      action of GA on renal histology, but it partially improved some of the above
      biochemical and physiological analytes, suggesting that addition of this mode of
      exercise to GA supplementation may improve further the benefits of GA
      supplementation.

PMID- 25048382
TI  - Blood pressure and pulse pressure effects on renal outcomes in the Veterans
      Affairs Diabetes Trial (VADT).
AB  - OBJECTIVE: Blood pressure (BP) control for renal protection is essential for
      patients with type 2 diabetes. Our objective in this analysis of Veterans Affairs
      Diabetes Trial (VADT) data was to learn whether on-study systolic BP (SBP),
      diastolic BP (DBP), and pulse pressure (PP) affected renal outcomes measured as
      albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate
      (eGFR). RESEARCH DESIGN AND METHODS: The VADT was a prospective, randomized study
      of 1,791 veterans with type 2 diabetes to determine whether intensive glucose
      control prevented major cardiovascular events. In this post hoc study, time
      varying covariate survival analyses and hazard ratios (HR) were used to determine
      worsening of renal outcomes. RESULTS: Compared with SBP 105-129 mmHg, the risk of
      ACR worsening increased significantly for SBP 130-139 mmHg (HR 1.88 [95% CI 1.28
      2.77]; P = 0.001) and for SBP >=140 mmHg (2.51 [1.66-3.78]; P < 0.0001). Compared
      with a PP range of 40-49 mmHg, PP <40 was associated with significantly lowered
      risk of worsening ACR (0.36 [0.15-0.87]; P = 0.022) and PP >=60 with
      significantly increased risk (2.38 [1.58-3.59]; P < 0.0001). Analyses of BP
      ranges associated with eGFR worsening showed significantly increased risk with
      rising baseline SBP and an interaction effect between SBP >=140 mmHg and on-study
      A1C. These patients were 15% more likely than those with SBP <140 mmHg to
      experience eGFR worsening (1.15 [1.00-1.32]; P = 0.045) for each 1% (10.9
      mmol/mol) A1C increase. CONCLUSIONS: SBP >=130 mmHg and PP >60 mmHg were
      associated with worsening ACR. The results suggest that treatment of SBP to <130
      mmHg may lessen ACR worsening. The interaction between SBP >=140 mmHg and A1C
      suggests that the effect of glycemic control on reducing progression of renal
      disease may be greater in hypertensive patients.

PMID- 25048381
TI  - The Look AHEAD Trial: bone loss at 4-year follow-up in type 2 diabetes.
AB  - OBJECTIVE: To determine whether an intensive lifestyle intervention (ILI)
      designed to sustain weight loss and improve physical fitness in overweight or
      obese persons with type 2 diabetes was associated with bone loss after 4 years of
      follow-up. RESEARCH DESIGN AND METHODS: This randomized controlled trial of
      intensive weight loss compared an ILI with a diabetes support and education (DSE)
      group among 1,309 overweight or obese subjects. Bone mineral density was assessed
      at baseline and after 1 year and 4 years of intervention. RESULTS: ILI was
      effective in producing significant weight loss (5.3% vs. 1.8% in ILI and DSE,
      respectively; P < 0.01) and increased fitness (6.4% vs. -0.8%) at year 4. In men,
      ILI participants had a greater rate of bone loss during the first year (-1.66%
      vs. -0.09% per year in ILI and DSE, respectively). Differences between groups
      were diminished by one-half after 4 years (-0.88% vs. -0.05% per year in ILI and
      DSE, respectively) but remained significant (P < 0.01). The difference in rate of
      hip bone loss between groups over 4 years was related to increased weight loss in
      ILI. Among women, the rate of bone loss did not differ between ILI and DSE after
      4 years. CONCLUSIONS: A 4-year weight loss intervention was significantly
      associated with a modest increase in bone loss at the hip in men but not in
      women.

PMID- 25048383
TI  - Efficacy and safety of the once-weekly GLP-1 receptor agonist albiglutide versus
      sitagliptin in patients with type 2 diabetes and renal impairment: a randomized
      phase III study.
AB  - OBJECTIVE: To evaluate weekly subcutaneous albiglutide versus daily sitagliptin
      in renally impaired patients with type 2 diabetes and inadequately controlled
      glycemia on a regimen of diet and exercise and/or oral antihyperglycemic
      medications. RESEARCH DESIGN AND METHODS: In this phase III, randomized, double
      blind, multicenter, 52-week study, the primary study end point was HbA1c change
      from baseline at week 26 in patients with renal impairment, as assessed with
      estimated glomerular filtration rate and categorized as mild, moderate, or severe
      (>=60 to <=89, >=30 to <=59, and >=15 to <=29 mL/min/1.73 m(2), respectively).
      Secondary end points included fasting plasma glucose (FPG), weight, achievement
      of treatment targets, hyperglycemic rescue, and safety. RESULTS: Baseline
      demographics were similar across treatment and renal impairment groups with
      overall mean age of 63.3 years, BMI of 30.4 kg/m(2), HbA1c of 8.2% (66 mmol/mol),
      and diabetes disease duration of 11.2 years. HbA1c change from baseline at week
      26 was significantly greater for albiglutide than sitagliptin (-0.83% vs. -0.52%,
      P = 0.0003). Decreases in HbA1c, FPG, and weight were seen through week 52. Time
      to hyperglycemic rescue through week 52 was significantly longer for albiglutide
      than sitagliptin (P = 0.0017). Results of safety assessments were similar between
      groups, and most adverse events (AEs) were mild or moderate. The incidences of
      gastrointestinal AEs for albiglutide and sitagliptin were as follows: overall,
      31.7%, 25.2%; diarrhea, 10.0%, 6.5%; nausea, 4.8%, 3.3%; and vomiting, 1.6%,
      1.2%, respectively. CONCLUSIONS: Once-weekly albiglutide therapy in renally
      impaired patients with type 2 diabetes provided statistically superior glycemic
      improvement with almost similar tolerability compared with daily sitagliptin
      therapy.

PMID- 25048384
TI  - Incidental findings from clinical sequencing in Greece: reporting experts'
      attitudes.
AB  - Unprecedented progress in sequencing technologies and decreasing cost have
      brought genomic testing into the clinical setting. At the same time, the debate
      in the literature concerning the return of incidental findings (IFs) has made
      this an important issue internationally. These developments reflect a shift in
      genetics that will also affect smaller countries, such as Greece, that are just
      starting to implement these technologies and may look to other countries for
      examples of good practice. Ten in-depth interviews were conducted with Greek
      experts in clinical sequencing. Previous experiences and attitudes toward IFs and
      clinical sequencing were investigated as well as views on the existing policy
      regarding managing genetic information generated through testing. . Interviews
      were analysed using thematic analysis. All participants reported the lack of any
      legal or other supportive mechanism. IFs are currently managed at a "local"
      level, i.e. within the clinic or the laboratory in an ad hoc way. All
      participants thought that clinically valid and actionable IFs should be returned,
      but always with caution and in respect to patients' wishes, although several
      experts reported returning IFs according to their clinical discretion. Experts
      reported that most patients ask for all tests available but they felt that more
      counselling is needed to understand and manage genetic information. Due to the
      lack of any supporting mechanisms, professionals in Greece, even those with
      established experience in the field of genetic and genomic testing, have
      difficulties dealing with IFs. All experts agreed that it is now time, before the
      full integration of genomic testing into everyday clinical practice, for guidance
      to help Greek physicians work with patients and their families when IFs are
      discovered. 

PMID- 25048385
TI  - Phosphoric acid catalyzed desymmetrization of bicyclic bislactones bearing an all
      carbon stereogenic center: total syntheses of (-)-rhazinilam and (-)-leucomidine
      B.
AB  - In the presence of a catalytic amount of an imidodiphosphoric acid,
      enantioselective desymmetrization of bicyclic bislactones by reaction with
      alcohols took place smoothly to afford enantiomerically enriched monoacids having
      an all-carbon stereogenic center. Concise catalytic enantioselective syntheses of
      both (-)-rhazinilam and (-)-leucomidine B were subsequently developed using (S)
      methyl 4-ethyl-4-formylpimelate monoacid as a common starting material. 

PMID- 25048387
TI  - Effects of dietary interventions on pregnancy outcomes: a systematic review and
      meta-analysis.
AB  - Dietary intake during pregnancy influences maternal health. Poor dietary
      practices during pregnancy have been linked to maternal complications. The
      objective was to determine the effect of dietary intervention before or during
      pregnancy on pregnancy outcomes. A systematic review was conducted without date
      restrictions. Randomised controlled trials (RCTs) evaluating whole diet or
      dietary components and pregnancy outcomes were included. Two authors
      independently identified papers for inclusion and assessed methodological
      quality. Meta-analysis was conducted separately for each outcome using random
      effects models. Results were reported by type of dietary intervention: (1)
      counselling; (2) food and fortified food products; or (3) combination (counseling
      + food); and collectively for all dietary interventions. Results were further
      grouped by trimester when the intervention commenced, nutrient of interest,
      country income and body mass index. Of 2326 screened abstracts, a total of 28
      RCTs were included in this review. Dietary counselling during pregnancy was
      effective in reducing systolic [standardised mean difference (SMD) -0.26, 95%
      confidence interval (CI) -0.45 to -0.07; P < 0.001] and diastolic blood pressure
      (SMD -0.57, 95% CI -0.75 to -0.38; P < 0.001). Macronutrient dietary
      interventions were effective in reducing the incidence of preterm delivery (SMD 
      0.19, 95% CI -0.34 to -0.04; P = 0.01). No effects were seen for other outcomes.
      Dietary interventions showed some small, but significant differences in pregnancy
      outcomes including a reduction in the incidence of preterm birth. Further high
      quality RCTs, investigating micronutrient provision from food, and combination
      dietary intervention, are required to identify maternal diet intakes that
      optimise pregnancy outcomes.

PMID- 25048388
TI  - Impact of stress on prefrontal glutamatergic, monoaminergic and cannabinoid
      systems.
AB  - Stress has been shown to have marked and divergent effects on learning and memory
      which involves specific brain regions, such as spatial and declarative memory
      involving the hippocampus, memory of emotional arousing experiences and fear
      involving the amygdala, and executive functions and fear extinction involving the
      prefrontal cortex or the PFC. Response to stress involves a coordinated
      activation of a constellation of physiological systems including the activation
      of the hypothalamic-pituitary-adrenal (HPA) axis and other modulatory
      neurotransmitters and signaling systems. This paper presents a concise review of
      the effects of stress and glucocorticoids on the glutamatergic and monoaminergic
      (including noradrenergic, dopaminergic, and serotonergic systems)
      neurotransmitter systems as well as endocannabinoid signaling. Because of the
      breadth of the scope of this topic, the review is limited to the effects of
      stress on these brain systems on the prefrontal cortex, and where relevant, the
      hippocampus and the amygdala. 

PMID- 25048386
TI  - Pain: a prevalent feature in patients with mucopolysaccharidosis. Results of a
      cross-sectional national survey.
AB  - BACKGROUND: While clinical observations suggest that many patients with
      mucopolysaccharidosis (MPS) experience chronic pain, few studies have assessed
      its extent and impact. We therefore investigated its prevalence in patients with
      all types of MPS in the Netherlands. We also examined the association between
      pain and health related quality of life (HRQoL) and other clinical variables.
      METHODS: We conducted a nationwide MPS survey that used questionnaires on MPS and
      disease-related symptoms (MPS-specific questionnaire), developmental level
      (Vineland Screener 0-6 years), quality of life (PedsQl and SF-36), and disability
      (Childhood Health Assessment Questionnaire). Depending on their age and
      developmental level, patients or their parents were asked to assess pain by
      keeping a pain diary for five consecutive days: either the Non-communicating
      Children's Pain Checklist - Revised (3-18 years intellectually disabled and
      children <8 years), the VAS-score (> 18 years), or the Faces Pain Scale - Revised
      (8-18 years). RESULTS: Eighty-nine MPS patients were invited, 55 of whom agreed
      to participate (response rate 62 %; median age 10.9 years, range 2.9-47.2 years).
      They covered a wide spectrum in all age groups, ranging from no pain to severe
      pain. Forty percent scored above the cut-off value for pain. Most reported pain
      sites were the back and hips. While the MPS III group experienced the highest
      frequency of pain (52.9 %), 50 % of patients with an intellectual disability
      seemed to experience pain, versus 30 % of patients with a normal intelligence.
      MPS patients scored much lower (i.e., more pain) than a random sample of the
      Dutch population on the bodily pain domain of the SF-36 scale and the PedsQl.
      CONCLUSION: With or without intellectual disabilities, many MPS patients
      experience pain. We recommend that standardized pain assessments are included in
      the regular follow-up program of patients with MPS.

PMID- 25048389
TI  - How does enhancing cognition affect human values? How does this translate into
      social responsibility?
AB  - The past decade has seen a rise in the use of different technologies aimed at
      enhancing cognition of normal healthy individuals. While values have been
      acknowledged to be an important aspect of cognitive enhancement practices, the
      discussion has predominantly focused on just a few values, such as safety, peer
      pressure, and authenticity. How are values, in a broader sense, affected by
      enhancing cognitive abilities? Is this dependent on the type of technology or
      intervention used to attain the enhancement, or does the cognitive domain
      targeted play a bigger role in how values are affected? Values are not only
      likely to be affected by cognitive enhancement practices; they also play a
      crucial role in defining the type of interventions that are likely to be
      undertaken. This paper explores the way values affect and are affected by
      enhancing cognitive abilities. Furthermore, it argues that knowledge of the
      interplay between values and cognitive enhancement makes a strong case for social
      responsibility around cognitive enhancement practices. 

PMID- 25048390
TI  - Deep brain stimulation: a principled and pragmatic approach to understanding the
      ethical and clinical challenges of an evolving technology.
AB  - DBS has emerged in the past few decades as a powerful clinical tool in the
      treatment of movement disorders such as dystonia and Parkinson's disease. As a
      result of its striking effects, the therapeutic utility of DBS has been
      investigated in a number of different neurological and neuropsychiatric
      conditions. Ethical discussion has accompanied this evolution of DBS and has led
      to the identification of a number of important ethical challenges. In this
      chapter, we review these challenges based on three of the key principles of
      biomedical ethics (autonomy, justice, and non-maleficence). Specifically, we
      adopt a pragmatic perspective by reviewing the ethical issues as they emerge
      within the context of Parkinson's disease, as this can serve to guide further
      ethical thinking on the future of DBS. Through this contextualization, we enrich
      the meaning of the Ethical principles and increase their specificity. We hope
      that this contribution will inform readers and also stimulate discussion related
      to areas where important questions remain unanswered and where further research
      would need to be undertaken to understand and enact ethical principles.

PMID- 25048391
TI  - [Consequences on women and their health of the possible reform of the abortion
      law].

PMID- 25048392
TI  - [Determinants of the use of different healthcare levels in the General System of
      Social Security in Health in Colombia and the Unified Health System in Brazil].
AB  - OBJECTIVE: To compare the use of different healthcare levels, and its
      determinants, in two different health systems, the General System of Social
      Security in Health (GSSSH) and the Unified Health System (UHS) in municipalities
      in Colombia and Brazil. METHODS: A cross-sectional study was carried out, based
      on a population survey in two municipalities in Colombia (n=2163) and two in
      Brazil (n=2155). Outcome variables consisted of the use of primary care services,
      outpatient secondary care services, and emergency care in the previous 3 months.
      Explanatory variables were need and predisposing and enabling factors. Bivariate
      and multivariate logistic regression analyses were performed by healthcare level
      and country. RESULTS: The determinants of use differed by healthcare level and
      country: having a chronic disease was associated with a greater use of primary
      and outpatient secondary care in Colombia, and was also associated with the use
      of emergency care in Brazil. In Colombia, persons enrolled in the contributory
      scheme more frequently used the services of the GSSSH than persons enrolled with
      subsidized contributions in primary and outpatient secondary care and more than
      persons without insurance in any healthcare level. In Brazil, the low-income
      population and those without private insurance more frequently used the UHS at
      any level. In both countries, the use of primary care was increased when persons
      knew the healthcare center to which they were assigned and if they had a regular
      source of care. Knowledge of the referral hospital increased the use of
      outpatient secondary care and emergency care. CONCLUSIONS: In both countries, the
      influence of the determinants of use differed according to the level of care
      used, emphasizing the need to analyze healthcare use by disaggregating it by
      level of care.

PMID- 25048393
TI  - Social housing conditions influence morphine dependence and the extinction of
      morphine place preference in adolescent mice.
AB  - BACKGROUND: Adolescent opioid abuse is on the rise, and current treatments are
      not effective in reducing rates of relapse. Our previous studies demonstrated
      that social housing conditions alter the acquisition rate of morphine conditioned
      place preference (CPP) in adolescent mice. Specifically, the acquisition rate of
      morphine CPP is slower in morphine-treated animals housed with drug-naive
      animals. Thus, here we tested the effect of social housing conditions on the
      development of morphine dependence and the extinction rate of an acquired
      morphine CPP. METHODS: Adolescent male mice were group-housed in one of two
      housing conditions. They were injected for 6 days (PND 28-33) with 20 mg/kg
      morphine. Morphine only mice are animals where all four mice in the cage received
      morphine. Morphine cage-mate mice are morphine-injected animals housed with drug
      naive animals. Mice were individually tested for spontaneous withdrawal signs by
      quantifying jumping behavior 4, 8, 24, and 48 h after the final morphine
      injection. Then, mice were conditioned to acquire morphine CPP and were tested
      for the rate of extinction. RESULTS: Morphine cage-mates express less jumping
      behavior during morphine withdrawal as compared to morphine only mice. As
      expected, morphine cage-mate animals acquired morphine CPP more slowly than the
      morphine only animals. Additionally, morphine cage-mates extinguished morphine
      CPP more readily than morphine only mice. CONCLUSIONS: Social housing conditions
      modulate morphine dependence and the extinction rate of morphine CPP. Extinction
      testing is relevant to human addiction because rehabilitations like extinction
      therapy may be used to aid human addicts in maintaining abstinence from drug use.

PMID- 25048394
TI  - Predictive factors for the efficacy of switch to oral hypoglycemic agents in
      Japanese type 2 diabetic patients with intensive insulin therapy temporarily
      introduced.
AB  - Some type 2 diabetic patients can maintain optimal glycemic control by oral
      hypoglycemic agents (OHA) after their uncontrolled hyperglycemia is corrected by
      a temporary introduction of insulin therapy. The objective of this study was to
      investigate the clinical predictors for the efficacy of OHA after intensive
      insulin therapy was temporarily introduced. We analyzed a retrospective database
      of 108 Japanese type 2 diabetic patients who underwent a 75-g oral glucose
      tolerance test (OGTT) after the temporary introduction of intensive insulin
      therapy, and tried the switch to OHA. The multivariate logistic regression
      analysis revealed that shorter diabetic duration, higher body mass index, and
      lower 2-h post meal glucose levels were independently associated with the
      efficacy of OHA (all p < 0.001). The C statistic of the multivariate model was
      calculated to be 0.86. The addition of 120-min insulinogenic index, calculated
      from 0-, 30-, 60-, and 120-min data during an OGTT, to the model significantly
      increased the C statistic to 0.91 (p = 0.025). Interestingly, omitting 30- and 60
      min data from the calculation of the index did not reduce the predictive
      performance. Furthermore, the ratio of 120-min insulin levels to 120-min glucose
      levels also provided a comparable predictive performance. In conclusion, 0- and
      120-min data during an OGTT, or even 120-min data alone, in combination with
      diabetic duration, body mass index, and 2-h post meal glucose levels were useful
      in predicting the efficacy of OHA after intensive insulin therapy in Japanese
      type 2 diabetic patients. 

PMID- 25048395
TI  - The first case of human protothecosis caused by Prototheca zopfii in Japan.
AB  - This report describes a fatal case Prototheca zopfii genotype 2 infection in an
      immunosuppressed patient. The patient was a 62-year-old housewife who presented
      general malaise in April 2011. Hairy cell leukemia was highly suspected.
      Chemotherapy was started because the patient developed severe pancytopenia in
      October 2011. Itraconazole capsules (100 mg/day) and trimethoprim (320 mg/day)
      plus sulfamethoxazole (1600 mg/day) combinations were orally administered for
      prophylaxis of fungal infections. Of BacT/ALERT 3D FA aerobic culture bottles and
      FN anaerobic culture bottles, only FA aerobic blood culture bottles produced
      positive reactions when the patient developed fever in January 2012. Gram
      staining of blood culture bottles revealed Gram-negative elliptical sporangia.
      Culturing on Sabouraud dextrose agar produced smooth and creamy white, yeast-like
      colonies. Partial DNA sequences of the nuclear 18S rDNA and 28S rDNA D1/D2
      domains of the isolated strain were identical to those of P. zopfii genotype 2.
      The MICs and minimal lethal concentrations of antifungals revealed that it was
      susceptible to amphotericin B and itraconazole. The patient died, at which time
      plasma (1 -> 3)-beta-D-glucan was positive (131 pg/mL). 

PMID- 25048396
TI  - Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche
      formation in hepatocellular carcinoma.
AB  - Poor prognosis of cancers, including hepatocellular carcinoma (HCC), is mainly
      associated with metastasis; however, the underlying mechanisms remain poorly
      understood. This article investigates the role of lysyl oxidase-like 2 (LOXL-2)
      in the biology of HCC metastasis. First, we showed that HCC metastasis relies on
      a collagen-modifying enzyme, LOXL2, which was significantly overexpressed in
      tumorous tissues and sera of HCC patients, indicating that LOXL2 may be a good
      diagnostic marker for HCC patients. Second, we delineated a complex, interlinked
      signaling network that involves multiple regulators, including hypoxia,
      transforming growth factor beta (TGF-beta), and microRNAs (miRNAs), converging to
      control the expression of LOXL2. We found not only that LOXL2 was regulated by
      hypoxia/hypoxia-inducible factor 1 alpha (HIF-1alpha), but also that TGF-beta
      activated LOXL2 transcription through mothers against decapentaplegic homolog 4
      (Smad4), whereas two frequently underexpressed miRNA families, miR-26 and miR-29,
      cooperatively suppressed LOXL2 transcription through interacting with the 3'
      untranslated region of LOXL2. Third, we demonstrated the imperative roles of
      LOXL2 in modifying the extracellular matrix components in the tumor
      microenvironment and metastatic niche of HCC. LOXL2 promoted intrahepatic
      metastasis by increasing tissue stiffness, thereby enhancing the cytoskeletal
      reorganization of HCC cells. Furthermore, LOXL2 facilitated extrahepatic
      metastasis by enhancing recruitment of bone-marrow-derived cells to the
      metastatic site. CONCLUSION: These findings integrate the clinical relevance,
      molecular regulation, and functional implications of LOXL2 in HCC metastasis.

PMID- 25048397
TI  - Novel method for the fabrication of a charge-transfer complex crystal by
      photoirradiation.
AB  - A novel method for the fabrication of a charge-transfer complex crystal was
      developed. Photoirradiation of a solution of TPP[Co(tbp)(CN)(2)] and
      TPP[Co(Pc)(CN)(2)] (tbp=tetrabenzoporphyrin, Pc=phthalocyanine,
      TPP=tetraphenylphosphonium) gave a molecular conducting crystal of a charge
      transfer complex TPP[Co(tbp)(CN)(2)](2), which was produced by the process in
      which the photoexcited electron in tbp was transferred from the LUMO of tbp to
      that of Pc.

PMID- 25048398
TI  - What is wrong with the tenets underpinning current management of severe traumatic
      brain injury?
AB  - The results of a recent randomized controlled trial comparing intracranial
      pressure (ICP) monitor-based treatment of severe traumatic brain injury (sTBI) to
      management without ICP monitoring prompt this skeptical reconsideration of the
      scientific foundation underlying current sTBI management. Much of current
      practice arises from research performed under conditions that are no longer
      relevant today. The definition of an episode of intracranial hypertension is
      incomplete, and the application of a fixed, universal ICP treatment threshold is
      poorly founded. Although intracranial hypertension is a valid indicator of
      disease severity, it remains to be demonstrated that lowering ICP improves
      outcome. Furthermore, sTBI has not been categorized on the basis of underlying
      pathophysiology despite the current capability to do so. Similar concerns also
      apply to manipulation of cerebral perfusion with respect to maintaining universal
      thresholds for contrived variables rather than tailoring treatment to monitored
      processes. As such, there is a failure to either optimize management approaches
      or minimize associated treatment risks for individual sTBI patients. The clinical
      and research TBI communities need to reassess many of the sTBI management
      concepts that are currently considered well established. 

PMID- 25048399
TI  - Dual electrochemical and physiological apoptosis assay detection of in vivo
      generated nickel chloride induced DNA damage in Caenorhabditis elegans.
AB  - Environmental nickel exposure is known to cause allergic reactions, respiratory
      illness, and may be responsible for some forms of cancer in humans. Nematodes are
      an excellent model organism to test for environmental toxins, as they are
      prevalent in many different environments. Nickel exposure has previously been
      shown to impact nematode life processes. In this study, Caenorhabditis elegans
      nematodes exposed to NiCl2 featured high levels of programmed cell death (PCD) in
      a concentration-dependent manner as measured by counting apoptotic corpses in the
      nematode germ line. A green fluorescent protein (GFP) reporter transgene was used
      that highlights cell corpse engulfment by fluorescence microscopy. Analysis of
      the reporter in a p53 mutant strain putatively indicates that the PCDs are a
      result of genomic DNA damage. In order to assay the potential genotoxic actions
      of NiCl2, DNA was extracted from nematodes exposed to increasing concentrations
      of NiCl2 and electrochemically assayed. In vivo damaged DNA was immobilized on
      pyrolytic graphite electrodes using the layer-by-layer (LbL) technique. Square
      wave voltammograms were obtained in the presence of redox mediator, ruthenium
      trisbipyridine (Ru(bpy)3(2+)), that catalytically oxidizes guanines in DNA.
      Oxidative peak currents were shown to increase as a function of NiCl2 exposure,
      which further suggests that the extracted DNA from nematodes exposed to the
      nickel was damaged. This report demonstrates that our electrochemical biosensor
      can detect damage at lower Ni concentrations than our physiological PCD assay and
      that the results are predictive of physiological responses at higher
      concentrations. Thus, a biological model for toxicity and animal disease can be
      assayed using an electrochemical approach. 

PMID- 25048401
TI  - The risks of not adjusting performance measures for sociodemographic factors.

PMID- 25048402
TI  - Supplementation dietary zinc levels on growth performance, carcass traits, and
      intramuscular fat deposition in weaned piglets.
AB  - This study was conducted to estimate dietary zinc (Zn) levels on growth
      performance, carcass traits, and intramuscular fat (IMF) deposition in weaned
      piglets. Sixty piglets were randomly divided into five groups, as follows:
      control (basal diet), Zn250, Zn380, Zn570, and Zn760 with supplementation of 250,
      380, 570, and 760 mg Zn/kg of the basal diet, respectively. The final weight,
      average daily gain (ADG), gain/feed (G/F), lean meat percentage, fat meat
      percentage, lean eye area, backfat thickness, and IMF content were dose
      dependently increased in all groups of Zn treatment. The serum total
      triglycerides (TG) and free fatty acid (FFA) were significantly higher in all Zn
      treatments than in the control. The enzyme activities of lipoprotein lipase
      (LPL), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were markedly
      higher, while enzyme activities of hormone-sensitive lipase (HSL) and carnitine
      palmitoyltransferase-1 (CPT-1) were significantly lower in all Zn treatments than
      in the control. The messenger RNA (mRNA) levels of sterol regulatory element
      binding protein 1 (SREBP-1), stearoyl-CoA desaturase (SCD), FAS, ACC, peroxisome
      proliferator-activated receptor gamma (PPARgamma), LPL, and adipocyte fatty acid
      binding protein (A-FABP) were significantly higher, while the mRNA levels of CPT
      1 and HSL were significantly lower in all Zn treatments compared with the
      control. These results indicated that high levels of Zn increased IMF
      accumulation by up-regulating intramuscular lipogenic and fatty acid transport
      gene expression and enzyme activities while down-regulating lipolytic gene
      expression and enzyme activities.

PMID- 25048403
TI  - Hair toxic element content in adult men and women in relation to body mass index.
AB  - The primary objective of the current study was to estimate the hair toxic metal
      content in adults in relation to body mass index. A total of 1,229 persons
      including 719 women and 510 men were examined. All subjects were divided into two
      age groups: 1 and 2 periods of adulthood. All men and women were also subdivided
      into groups in relation to their values of body mass index (BMI): underweight,
      normal weight, overweight and obese. Hair aluminium (Al), beryllium (Be), cadmium
      (Cd), mercury (Hg), lead (Pb) and tin (Sn) content was evaluated using mass
      spectrometry with inductively coupled plasma. It has been shown that increase in
      body weight is accompanied by elevated hair cadmium content in women. At the same
      time, no significant alteration of hair cadmium concentration was observed in
      males. Higher values of scalp hair mercury and lead content were observed in men
      and women with increased body mass index independently of their age. BMI-related
      elevation of hair tin content was registered only in men of the first period of
      adulthood. A significant correlation between hair metal content and the values of
      BMI was observed for mercury independently of the gender of the subjects, whereas
      BMI values correlated significantly with hair cadmium levels in women and lead
      and tin levels in men. It has been also estimated that hair cadmium, mercury and
      lead levels in men exceed the respective values in women. 

PMID- 25048404
TI  - Growth and characterization of Cadmium Thiosemicarbazide Bromide crystals for
      antibacterial and nonlinear optical applications.
AB  - Semiorganic nonlinear optical crystals of Cadmium Thiosemicarbazide Bromide was
      grown by slow evaporation solution growth technique. The unit cell parameters
      were estimated by subjecting the crystals to single crystal X-ray diffraction.
      The grown crystals were subjected to Powder X-ray diffraction for analyzing the
      crystalline nature of the sample. FTIR studies reveal the functional groups and
      the optical characters were analyzed by UV-Vis spectral studies. Mechanical
      stability of the sample was assessed by Vicker's micro hardness test. The
      presence of surface dislocations was identified by chemical etching technique.
      Antibacterial study was carried out against ACDP declared harmful pathogens. SHG
      efficiency of CTSB crystal was tested using Nd: YAG laser and it was found to be
      ~1.8 times that of potassium dihydrogen phosphate.

PMID- 25048400
TI  - The role of RecQ helicases in non-homologous end-joining.
AB  - DNA double-strand breaks are highly toxic DNA lesions that cause genomic
      instability, if not efficiently repaired. RecQ helicases are a family of highly
      conserved proteins that maintain genomic stability through their important roles
      in several DNA repair pathways, including DNA double-strand break repair. Double
      strand breaks can be repaired by homologous recombination (HR) using sister
      chromatids as templates to facilitate precise DNA repair, or by an HR-independent
      mechanism known as non-homologous end-joining (NHEJ) (error-prone). NHEJ is a non
      templated DNA repair process, in which DNA termini are directly ligated.
      Canonical NHEJ requires DNA-PKcs and Ku70/80, while alternative NHEJ pathways are
      DNA-PKcs and Ku70/80 independent. This review discusses the role of RecQ
      helicases in NHEJ, alternative (or back-up) NHEJ (B-NHEJ) and microhomology
      mediated end-joining (MMEJ) in V(D)J recombination, class switch recombination
      and telomere maintenance.

PMID- 25048405
TI  - Vibrational dephasing and frequency shifts of hydrogen-bonded pyridine-water
      complexes.
AB  - In this paper we present the picosecond vibrational dynamics and Raman shifts of
      hydrogen-bonded pyridine-water complexes present in aqueous solutions in a wide
      concentration range from dense to extreme dilute solutions. We studied the
      vibrational dephasing and vibrational frequency modulation by calculating time
      correlation functions of vibrational relaxation by fits in the frequency domain.
      The concentration induced variations in bandwidths, band frequencies and
      characteristic dephasing times have been estimated and interpreted as effects due
      to solute-solvent interactions. The time-correlation functions of vibrational
      dephasing were obtained for the ring breathing mode of both "free" and hydrogen
      bonded pyridine molecules and it was found that sufficiently deviate from the
      Kubo model. There is a general agreement in the whole concentration range with
      the modeling proposed by the Rothschild approach, which applies to complex
      liquids. The results have shown that the reorientation of pyridine aqueous
      solutions is very slow and hence in both scattering geometries only vibrational
      dephasing is probed. It is proposed that the spectral changes depend on the
      perturbations induced by the dynamics of the water molecules in the first
      hydration cell and water in bulk, while at extreme dilution conditions, the
      number of bulk water molecules increases and the interchange between molecules
      belonging to the first hydration cell may not be the predominant modulation
      mechanism. The evolution of several parameters, such as the characteristic times,
      the percentage of Gaussian character in the peak shape and the a parameter are
      indicative of drastic variations at extreme dilution revealing changes in the
      vibrational relaxation of the pyridine complexes in the aqueous environment. The
      higher dilution is correlated to diffusion of water molecules into the reference
      pyridine system in agreement with the jump diffusion model, while at extreme
      dilutions, almost all pyridine molecules are elaborated in hydrogen bonding. The
      results are discussed in the framework of the current phenomenological status of
      the field. 

PMID- 25048406
TI  - Studies on the growth, structural, spectral and third-order nonlinear optical
      properties of ammonium 3-carboxy-4-hydroxy benzenesulfonate monohydrate single
      crystal.
AB  - An organic nonlinear optical bulk single crystal, Ammonium 3-carboxy-4-hydroxy
      benzenesulfonate monohydrate (ACHBS) was successfully grown by solution growth
      technique. Single crystal X-ray diffraction study confirms that, the grown
      crystal belongs to P21/c space group. Powder X-ray diffraction and high
      resolution X-ray diffraction analyses revealed the crystallinity of the grown
      crystal. Infrared spectral analysis showed the vibrational behavior of chemical
      bonds and its functional groups. The thermal stability and decomposition stages
      of the grown crystal were studied by TG-DTA analysis. UV-Visible transmittance
      studies showed the transparency region and cut-off wavelength of the grown
      crystal. The third-order nonlinear optical susceptibility of the grown crystal
      was estimated by Z-scan technique using He-Ne laser source. The mechanical
      property of the grown crystal was studied by using Vicker's microhardness test.

PMID- 25048407
TI  - Impact of prior chronic statin therapy and high-intensity statin therapy at
      discharge on circulating endothelial progenitor cell levels in patients with
      acute myocardial infarction: a prospective observational study.
AB  - BACKGROUND: Endothelial progenitor stem cells (EPCs) are mobilized to the
      peripheral circulation in response to myocardial ischemia, playing a crucial role
      in vascular repair. Statins have been shown to stimulate EPCs. However, neither
      the impact of previous statin therapy on EPC response of acute myocardial
      infarction (AMI) patients nor the effect of post-AMI high-intensity statin
      therapy on the evolution of circulating EPC levels has yet been addressed.
      Therefore, we aimed to compare circulating EPC levels between patients receiving
      long-term statin therapy before the AMI and statin-naive patients and to assess
      the impact of high-intensity statin therapy at discharge on the evolution of
      circulating EPCs post-AMI. METHODS: This is a prospective observational study of
      100 AMI patients. Circulating EPCs (CD45dimCD34 + KDR + cells) and their
      subpopulation coexpressing the homing marker CXCR4 were quantified by the high
      performance flow cytometer FACSCanto II in whole blood, in two different moments:
      within the first 24 h of admission and 3 months post-AMI. Patients were followed
      up clinically for 2 years. RESULTS: Patients previously treated with statins had
      significantly higher levels of EPCs coexpressing CXCR4 (1.9 +/- 1.4 vs. 1.3 +/-
      1.0 cells/1,000,000 events, p = 0.031) than statin-naive patients. In addition,
      the subanalysis of diabetics (N = 38) also revealed that patients previously on
      statins had significantly greater numbers of both CD45dimCD34 + KDR + CXCR4+
      cells (p = 0.024) and CD45dimCD34 + KDR + CD133+ cells (p = 0.022) than statin
      naive patients. Regarding the evolution of EPC levels after the AMI, patients not
      on a high-intensity statin therapy at discharge had a significant reduction of
      CD45dimCD34 + KDR + and CD45dimCD34 + KDR + CXCR4+ cells from baseline to 3
      months follow-up (p = 0.031 and p = 0.005, respectively). However, patients
      discharged on a high-intensity statin therapy maintained circulating levels of
      all EPC populations, presenting at 3 months of follow-up significantly higher EPC
      levels than patients not on an intensive statin therapy. Moreover, the high
      intensity statin treatment group had significantly better clinical outcomes
      during the 2-year follow-up period than patients not discharged on a high
      intensity statin therapy. CONCLUSION: Chronic statin therapy prior to an AMI
      strongly enhances the response of EPCs to myocardial ischemia, even in diabetic
      patients. Furthermore, high-intensity statin therapy after an AMI prevents the
      expected decrease of circulating EPC levels during follow-up. These results
      reinforce the importance of an early and intensive statin therapy in AMI
      patients.

PMID- 25048408
TI  - Impact of cytochrome P450 inducers with or without inhibitors on the serum
      clobazam level in patients with antiepileptic polypharmacy.
AB  - PURPOSE: The aim of this study was to evaluate the effect of cytochrome P450
      (CYP) inducers/inhibitors on the pharmacokinetics of clobazam (CLB) in patients
      receiving antiepileptic polypharmacy. METHODS: A total of 2,504 samples obtained
      from 1,280 patients for routine therapeutic drug monitoring were retrospectively
      reviewed. These samples were grouped according to the antiepileptic drug regimens
      or age, and then the concentration to dose (CD) ratio (serum level (ng/ml)
      divided by dose (mg/kg)) of CLB was calculated for comparison. RESULTS: The mean
      CD ratio of CLB in adult patients using enzyme inducers (phenytoin (PHT),
      carbamazepine (CBZ), and phenobarbital (PB) alone or in combination) was 60.8%
      lower than the ratio in patients without inducers. Among the inducers, patients
      using PHT had a significantly lower CD ratio than patients using PB or CBZ (p <
      0.001). When PHT was combined with CBZ and/or PB, no additive or synergetic
      interactions was observed. The CD ratio of CLB in pediatric patients using
      inducers was 44.3% lower than in patients without inducers. The influence of
      inducers was unchanged regardless of the child's age, and the effect was stronger
      in adults than in pediatric patients. Other than inducers, valproic acid (VPA)
      additively reduced the CD ratio, whereas concomitant use of stiripentol
      significantly elevated the CD ratio in patients receiving VPA. In contrast,
      CYP3A4 substrates, such as zonisamide and topiramate, had little influence on the
      CD ratio of CLB. CONCLUSION: We identified an impact of CYP inducers/inhibitors
      on the CLB concentration. Our findings demonstrated that clinically relevant
      interactions occur between CLB and concomitant antiepileptic drugs.

PMID- 25048409
TI  - Impulse control and repetitive behaviors in Parkinson's disease - are there
      differences in the relation to dopamine agonist treatment?

PMID- 25048410
TI  - Acute bilateral radial palsy responsive to intravenous immunoglobulins.

PMID- 25048412
TI  - The regulatory network controlling spore formation in Clostridium difficile.
AB  - Clostridium difficile, a Gram-positive, anaerobic, spore-forming bacterium, is a
      major cause of nosocomial infections such as antibiotic-associated diarrhea.
      Spores are the vector of its transmission and persistence in the environment.
      Despite the importance of spores in the infectious cycle of C. difficile, little
      was known until recently about the control of spore development in this
      enteropathogen. In this review, we describe recent advances in our understanding
      of the regulatory network controlling C. difficile sporulation. The comparison
      with the model organism Bacillus subtilis highlights major differences in the
      signaling pathways between the forespore and the mother cell and a weaker
      connection between morphogenesis and gene expression. Indeed, the activation of
      the SigE regulon in the mother cell is partially independent of SigF although the
      forespore protein SpoIIR, itself partially independent of SigF, is essential for
      pro-SigE processing. Furthermore, SigG activity is not strictly dependent on
      SigE. Finally, SigG is dispensable for SigK activation in agreement with the
      absence of a pro-SigK sequence. The excision of the C. difficile skin element is
      also involved in the regulation of SigK activity. The C. difficile sporulation
      process might be a simpler, more ancestral version of the program characterized
      for B. subtilis.

PMID- 25048411
TI  - The role of interleukin-1 family members in the host defence against Aspergillus
      fumigatus.
AB  - The interleukin (IL)-1 family consists of 11 members, which all play significant
      roles in regulating inflammatory responses in the host. IL-1alpha and IL-1beta
      exert potent pro-inflammatory effects and are key players in the recruitment of
      neutrophils to the site of inflammation. Protective anti-Aspergillus host
      responses during the early stages of invasive aspergillosis are critically
      dependent on neutrophil recruitment, and several lines of evidence support that
      there is an important role for IL-1 in this process. However, IL-1-mediated
      inflammation needs to be tightly regulated, since uncontrolled inflammation can
      result in inflammatory pathology and thereby be detrimental for the host.
      Aspergillus-induced IL-1-mediated inflammation could therefore be amendable for
      IL-1 blockade under specific circumstances. This review describes the current
      understanding of the role of IL-1 family members in the host response against
      Aspergillus fumigatus and highlights the importance of balanced IL-1 responses in
      aspergillosis. 

PMID- 25048413
TI  - "Dying a hero": parents' and young people's discourses on concurrent sexual
      partnerships in rural Tanzania.
AB  - BACKGROUND: Concurrent sexual partnerships (CSPs) have been speculated to drive
      the HIV pandemic in many sub-Saharan African countries. We have limited
      understanding of how people think and talk about CSPs, how beliefs are
      transmitted across generations, and how this might affect the practice. This
      paper explores these issues to understand how CSPs are perpetuated and help
      identify opportunities for interventions to modify them. METHODS: The study
      employed an ethnographic research design involving: participant observation in 10
      households, 60 in-depth interviews (IDIs), and nine participatory focus group
      discussions (FGDs). Participants were young people aged 14-24 and parents/carers
      of young people within this age group. The 60 IDIs were conducted with: 17
      fathers, 13 mothers, 13 young men and 17 young women (six of whom had had
      unplanned pregnancies and 11 had no children). The nine FGDs were conducted with
      groups of: fathers (2), mothers (2), young women (2), and young men (3). A
      discourse analysis was carried out with all the transcripts. Data were analysed
      with the aid of NVIVO 8 software. RESULTS: Six distinct discourses were
      identified from the way participants talked about CSPs and the norms driving the
      practice: 1) predatory masculine sexuality; 2) masculine respectability; 3)
      feminine respectability; 4) empowered modern women; 5) traditional health
      beliefs; 6) public health. Discourses legitimating CSPs were drawn on and
      reproduced primarily by young people and the media and only indirectly by
      parents. Discourses discouraging CSPs were used primarily by parents, religious
      leaders and learning institutions and only indirectly by young people themselves.
      CONCLUSION: Better knowledge of the discourses through which young people CSPs,
      and how these discourses are transmitted across generations, might help develop
      "culturally compelling" interventions that modify these discourses to enhance
      sexual health.

PMID- 25048414
TI  - Neuropsychological performance of patients with soft bipolar spectrum disorders.
AB  - OBJECTIVES: There is much evidence that shows that a substantial number of
      individuals with DSM-IV-defined unipolar depression (UP) manifest hypomanic sub
      syndrome and bipolar diathesis. Other definitions have conceptualized the term
      soft bipolar spectrum (SBP) for these individuals. Little is known about the
      cognitive profiles of individuals with SBP. We hypothesized that they are
      representative of individuals with bipolar II disorder and are different from
      that of 'strict' UP. METHODS: Consecutive referrals suffering major depressive
      episodes were categorically assigned to groups of either bipolar I disorder (n =
      98), bipolar II disorder (n = 138), or UP (n = 300). Based on the SBP criteria by
      Akiskal and Pinto (17), patients with UP were subdivided into 81 SBP and 219
      strict UP. We administered self- and clinician-administered scales to evaluate
      affective temperaments, and neuropsychological tests to assess seven cognitive
      domains. RESULTS: Patients with SBP performed significantly better than strict UP
      patients in the domains of processing speed (p = 0.002), visual-spatial memory (p
      = 0.017), and verbal working memory (p = 0.017). Compared to patients with
      bipolar I disorder, patients with SBP were significantly better in set shifting
      (p < 0.001) and visual-spatial memory (p = 0.042). Patients with SBP performed
      similarly to patients with bipolar II disorder in all of the cognitive domains
      tested (p > 0.05). There was a group * cognitive domain interaction effect
      between bipolar I disorder, bipolar II disorder, SBP, and strict UP groups
      [Pillai's F = 2.231, df = (18,1437), p = 0.002]. CONCLUSIONS: Our data suggest
      that patients with SBP differ from patients with UP not only in external
      validators (e.g., family history of bipolar disorder) and hypomanic symptoms, but
      also in neuropsychological performance and that the profiles of cognitive
      functioning were different across bipolar I disorder and 'bipolar II spectrum'
      that subsumes bipolar II disorder and SBP.

PMID- 25048415
TI  - Hemolytic crisis in a G6PD-deficient infant after ingestion of pumpkin.
AB  - A 8 month-old infant presented with acute onset of severe jaundice, anemia
      requiring transfusion and Glucose-6-Phosphate Dehydrogenase deficiency. The
      infant did not take drugs, he did not consume fava beans, but fava beans DNA was
      found on pumpkin he consumed the day before jaundice onset. This is the first
      case of hemolysis triggered by ingestion of food cross-contaminated with fava
      beans.

PMID- 25048416
TI  - Interaction between the Val158Met catechol-O-methyltransferase gene variant and
      second-generation antipsychotic treatment on blood pressure in children.
AB  - Second-generation antipsychotic (SGA) medications are associated with
      cardiometabolic risk factors such as obesity and elevated blood pressure (BP) in
      some individuals. The goal of this study is to determine whether the Val158Met
      variant (rs4680) in the catechol-O-methyltransferase (COMT) gene, associated with
      BP in adults, is associated with elevated BP in SGA-treated children. A cross
      sectional population of SGA-treated (n=134) and SGA-naive (n=168) children, ?18
      years of age, were genotyped and assessed for markers of cardiometabolic health.
      An interaction was found between SGA treatment and COMT genotype for BP. After
      adjusting for covariates, SGA-treated children with the Met allele had higher
      systolic and diastolic BP (P=0.014 and P=0.034, respectively), and higher fasting
      glucose concentrations (P=0.030) compared with children with the Val/Val
      genotype. This was not observed in SGA-naive children. The Met allele of the COMT
      Val158Met variant may identify SGA-treated children at risk for elevated BP and
      fasting blood glucose concentrations. 

PMID- 25048418
TI  - Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2
      styrylchromones using 1D and 2D NMR spectroscopy.

PMID- 25048419
TI  - Direct photocatalysis for organic synthesis by using plasmonic-metal
      nanoparticles irradiated with visible light.
AB  - Recent advances in direct-use plasmonic-metal nanoparticles (NPs) as
      photocatalysts to drive organic synthesis reactions under visible-light
      irradiation have attracted great interest. Plasmonic-metal NPs are characterized
      by their strong interaction with visible light through excitation of the
      localized surface plasmon resonance (LSPR). Herein, we review recent developments
      in direct photocatalysis using plasmonic-metal NPs and their applications. We
      focus on the role played by the LSPR of the metal NPs in catalyzing organic
      transformations and, more broadly, the role that light irradiation plays in
      catalyzing the reactions. Through this, the reaction mechanisms that these light
      excited energetic electrons promote will be highlighted. This review will be of
      particular interest to researchers who are designing and fabricating new
      plasmonic-metal NP photocatalysts by identifying important reaction mechanisms
      that occur through light irradiation. 

PMID- 25048417
TI  - Therapeutic implications of novel mutations of the RFX6 gene associated with
      early-onset diabetes.
AB  - Identification of the genetic defect underlying early-onset diabetes is important
      for determining the specific diabetes subtype, which would then permit
      appropriate treatment and accurate assessment of recurrence risk in offspring.
      Given the extensive genetic and clinical heterogeneity of the disease, high
      throughput sequencing might provide additional diagnostic potential when Sanger
      sequencing is ineffective. Our aim was to develop a targeted next-generation
      assay able to detect mutations in several genes involved in glucose metabolism.
      All 13 known MODY genes, genes identified from a genome-wide linkage study or
      genome-wide association studies as increasing the risk of type 2 diabetes and
      genes causing diabetes in animal models, were included in the custom panel. We
      selected a total of 102 genes by performing a targeting re-sequencing in 30
      patients negative for mutations in the GCK, HNF1alpha, HNF4alpha, HNF1beta and
      IPF1 genes at the Sanger sequencing analysis. Previously unidentified variants in
      the RFX6 gene were found in three patients and in two of them we also detected
      rare variants in WFS1 and ABCC8 genes. All patients showed a good therapeutic
      response to dipeptidyl peptidase-4 (DPP4) inhibitors. Our study reveals that next
      generation sequencing provides a highly sensitive method for identification of
      variants in new causative genes of diabetes. This approach may help in
      understanding the molecular etiology of diabetes and in providing more
      personalized treatment for each genetic subtype. 

PMID- 25048420
TI  - Association between indices of clinically-defined periodontitis and self-reported
      history of systemic medical conditions.
AB  - AIM: The aim of the current research was to investigate whether possible
      associations exist between indices of clinically-defined periodontitis and
      several systemic medical conditions in outpatients referred to a special hospital
      clinic. METHODS: The study sample consisted of 3360 outpatients aged 45-65 years.
      Data were collected by means of an oral clinical examination and a self
      administered questionnaire. Statistical analysis of the questionnaire items was
      done with Fisher's exact test and the logistic regression model to assess
      possible associations between systemic medical conditions as independent
      variables, and the relative frequency of periodontal pockets >=5 mm and clinical
      attachment loss (CAL) of >=6 mm as dependent variables. RESULTS: The depth of
      periodontal pockets was significantly associated with male sex, the presence of
      vascular disease, hypertension, stroke, heart attack, diabetes mellitus, other
      endocrine diseases, thyroid disease, respiratory allergies, and rheumatoid
      arthritis. CAL was significantly associated with the mentioned conditions, and
      also infective endocarditis and chronic obstructive pulmonary disease, but not
      other endocrine and thyroid disease. CONCLUSIONS: The findings confirm the
      results from previous investigations in which a number of systemic medical
      conditions were significantly associated with probing pocket depth and/or CAL.

PMID- 25048421
TI  - Polycystic ovaries is a disproportionate signal in pharmacovigilance data mining
      of second generation antipsychotics.

PMID- 25048422
TI  - Blunted cortisol awakening response in people at ultra high risk of developing
      psychosis.
AB  - BACKGROUND: There is a consensus that stress plays a role in the onset of
      psychosis but the precise underlying mechanism remains unclear. The hypothalamic
      pituitary-adrenal (HPA) axis is hypothesised to mediate the relationship between
      stress and psychosis and evidence indicates a potential role for the stress
      hormone cortisol as a biomarker of psychosis risk. OBJECTIVE: We explored this
      hypothesis by examining the HPA axis in people at ultra-high risk (UHR) for
      psychosis and its relationship to symptoms. METHOD: UHR (n=52) and healthy
      control (HC; n=42) participants were compared on two measures of HPA axis
      function: cortisol response to awakening and daytime cortisol release. RESULTS:
      UHR participants displayed a blunted cortisol awakening response compared with HC
      participants. No group difference in daytime cortisol levels was found, nor were
      any associations between cortisol measures and symptoms. CONCLUSIONS: These
      findings are broadly consistent with previous studies and neurobiological models
      which propose that stress and the HPA axis are involved in the onset of
      psychosis, although they raise further questions regarding the precise nature of
      this involvement.

PMID- 25048423
TI  - Association of intracortical inhibition with social cognition deficits in
      schizophrenia: Findings from a transcranial magnetic stimulation study.
AB  - Abnormal cortical-inhibition has been hypothesized to underlie social-cognition
      deficits in schizophrenia. Studies using transcranial magnetic stimulation (TMS)
      as a neurophysiological probe have demonstrated cortical-inhibition deficits in
      this group. We compared TMS-measured short- and long-interval intracortical
      inhibition (SICI & LICI) in antipsychotic-naive (n=33) and medicated (n=21)
      schizophrenia patients and in healthy comparison subjects (n=45). We also studied
      the association between cortical-inhibition and social-cognition deficits in the
      patients. Antipsychotic-naive patients had significant deficits in SICI (i.e.,
      less inhibitory response). In this group, SICI had significant inverse
      correlations with emotion processing and a global social-cognition score.
      Impaired intracortical-inhibition may thus contribute to social-cognition
      deficits in schizophrenia. 

PMID- 25048424
TI  - Is there a binding deficit in working memory in patients with schizophrenia? A
      meta-analysis.
AB  - In schizophrenia (SZ), a specific binding deficit in working memory (WM) has not
      yet been demonstrated, given that studies with various methodologies were
      conducted and the results obtained were heterogeneous. Thus, a meta-analysis of
      10 WM studies was performed. Effect sizes were calculated for binding and control
      conditions. Analyses disclosed significantly lower scores in SZ patients relative
      to controls for both binding and control conditions. In addition, analyses
      revealed no greater impairments for the binding condition than for the control
      condition in SZ patients. Our meta-analysis suggests that there is no specific
      deficit of binding in WM in SZ. 

PMID- 25048425
TI  - Childhood Epstein-Barr Virus infection and subsequent risk of psychotic
      experiences in adolescence: a population-based prospective serological study.
AB  - BACKGROUND: Several studies suggest a link between early-life infection and adult
      schizophrenia. Cross-sectional studies have reported: (1) increased prevalence of
      Epstein-Barr Virus (EBV), a member of the Herpesviridae family in schizophrenia;
      (2) a possible role of Herpes simplex virus in cognitive dysfunction in
      schizophrenia and healthy controls. We report a longitudinal serological study of
      early-life EBV infection, childhood IQ, and subsequent risk of psychotic
      experiences (PE) in adolescence. METHODS: Serum antibodies to EBV (anti-VCA IgG)
      were measured in 530 participants from the ALSPAC cohort at age 4 years.
      Assessments for IQ at age 9 and PE at age 13 were attended by 401 and 366 of
      these individuals, respectively. Logistic regression calculated odds ratio (OR)
      for PE in EBV-exposed, compared with unexposed group. Mean IQ scores were
      compared between these groups; effect of IQ on the EBV-PE association was
      examined. Potential confounders included age, gender, ethnicity, social class,
      household crowding, and concurrent depression and anxiety. RESULTS: About 25% of
      the sample was exposed to EBV at age 4. EBV exposure was associated with
      subsequent risk of definite PE in adolescence; OR 5.37 (95% CI 1.71-16.87), which
      remained significant after confounding adjustment. EBV-exposed individuals
      compared with unexposed performed worse on all IQ measures; mean difference in
      full-scale IQ 4.15 (95% CI 0.44-7.87); however, this was explained by socio
      demographic differences. The EBV-PE association was not explained by IQ.
      CONCLUSIONS: Early-life exposure to EBV is associated with PE in adolescence,
      consistent with a role of infection/immune dysfunction in the aetiology of
      psychosis.

PMID- 25048427
TI  - Does paternal mental health in pregnancy predict physically aggressive behavior
      in children?
AB  - The aim was to study the association between paternal mental health and
      physically aggressive behavior in children. This study is based on 19,580 father
      child dyads from the Norwegian Mother and Child Cohort Study (MoBa). Fathers'
      mental health was assessed by self-report (Symptom Checklist-5, SCL-5) in week 17
      or 18 of gestation. Children's behavior (hitting others) was obtained by mothers'
      reports. A multinomial logistic regression model was performed. Expectant
      fathers' high level of psychological distress was found to be a significant risk
      factor only for girls hitting, adjusted OR = 1.46 (1.01-2.12), p = 0.043, but not
      for boys. High levels of mental distress in fathers predict their daughters'
      hitting at 5 years of age. 

PMID- 25048428
TI  - Multifunctional Schottky-diode circuit comprising palladium/molybdenum disulfide
      nanosheet.
AB  - Many electron devices using two-dimensional dichalcogenide MoS2 have been
      reported beyond graphene, but those were mostly field-effect transistors except
      few while P-N or Schottky diode form devices should be also important. In the
      present study, we have fabricated a Pd-driven MoS2 Schottky diode and its related
      circuits for multifunctional applications: dynamic electrical rectifier, visible
      light sensor, and hydrogen gas sensor.

PMID- 25048429
TI  - Association of IL23R and ATG16L1 with susceptibility of Crohn's disease in
      Chinese population.
AB  - OBJECTIVES: To investigate whether gene polymorphisms of ATG16L1 and IL23R are
      associated with the susceptibility of Crohn's disease (CD) in Chinese population.
      METHODS: A total of 420 patients with CD and 450 age- and sex-matched healthy
      volunteers from Chinese Han population were included in this study. Single
      nucleotide polymorphisms (SNPs) rs2241880 of ATG16L1 and rs11209026, rs1004819,
      and rs1495965 of IL23R were genotyped. The differences of genotype and allele
      distributions between CD patients and healthy controls were assessed using the
      Chi-squared test. Besides, subgroup analysis of disease groups was performed
      using the Chi-squared test. RESULTS: For ATG16L1, patients were found to have
      significantly higher proportion of genotype GG (18.3%), when compared with the
      normal controls (12.4%). Allele G was found to be the risk allele for the disease
      (34.3% vs. 29.0%, p = 0.016) with an odds ratio of 1.18. For IL23R, all three
      SNPs were found not to be associated with the development of CD. None of these
      four SNPs was found to be associated with the clinical features of the patients,
      including age at diagnosis, disease location, and behavior. CONCLUSION: The
      original genome-wide association studies finding on ATG16L1 gene should be robust
      and this gene does play a role in the pathogenesis of CD in the Chinese
      population. However, the role of IL23R gene in the occurrence of CD remains
      obscure.

PMID- 25048426
TI  - Efficient linkage mapping using exome capture and extreme QTL in schistosome
      parasites.
AB  - BACKGROUND: Identification of parasite genes that underlie traits such as drug
      resistance and host specificity is challenging using classical linkage mapping
      approaches. Extreme QTL (X-QTL) methods, originally developed by rodent malaria
      and yeast researchers, promise to increase the power and simplify logistics of
      linkage mapping in experimental crosses of schistosomes (or other helminth
      parasites), because many 1000s of progeny can be analysed, phenotyping is not
      required, and progeny pools rather than individuals are genotyped. We explored
      the utility of this method for mapping a drug resistance gene in the human
      parasitic fluke Schistosoma mansoni. RESULTS: We staged a genetic cross between
      oxamniquine sensitive and resistant parasites, then between two F1 progeny, to
      generate multiple F2 progeny. One group of F2s infecting hamsters was treated
      with oxamniquine, while a second group was left untreated. We used exome capture
      to reduce the size of the genome (from 363 Mb to 15 Mb) and exomes from pooled F2
      progeny (treated males, untreated males, treated females, untreated females) and
      the two parent parasites were sequenced to high read depth (mean = 95-366*) and
      allele frequencies at 14,489 variants compared. We observed dramatic enrichment
      of alleles from the resistant parent in a small region of chromosome 6 in drug
      treated male and female pools (combined analysis: Z = 11.07, p = 8.74 * 10(-29)).
      This region contains Smp_089320 a gene encoding a sulfotransferase recently
      implicated in oxamniquine resistance using classical linkage mapping methods.
      CONCLUSIONS: These results (a) demonstrate the utility of exome capture for
      generating reduced representation libraries in Schistosoma mansoni, and (b)
      provide proof-of-principle that X-QTL methods can be successfully applied to an
      important human helminth. The combination of these methods will simplify linkage
      analysis of biomedically or biologically important traits in this parasite.

PMID- 25048430
TI  - Half-time re-warm up increases performance capacity in male elite soccer players.
AB  - This study investigated the acute effects of a half-time re-warm up on
      performance and movement patterns in soccer match play. Using a crossover design,
      22 professional male players performed traditional passive rest (CON) or a low
      intensity re-warm up (RW) during the half-time period of two soccer matches.
      Before and after the first half and before the second half, maximal sprint and
      jump performance were evaluated. Time-motion analysis of the first 15 min of each
      half was conducted. Sprint and jump performance were reduced (P < 0.05) by 2.6%
      and 7.6%, respectively, during the half-time period in CON, whereas sprint
      performance was maintained and the decrement in jump performance (3.1%; P < 0.05)
      was lower after RW. No significant interaction for high-intensity running was
      observed, but less defensive high-intensity running was observed after RW than
      CON (0.14 +/- 0.06 vs 0.22 +/- 0.07 km; P < 0.01). Moreover, RW had more
      possession of the ball in the beginning of the second half. In conclusion,
      traditional passive half-time rest leads to impaired sprint and jump performance
      during the initial phase of the second half in professional soccer players
      whereas a re-warm up effectively attenuates such deteriorations. Less defensive
      high-intensity running and more ball possession were observed after RW,
      indicating a game advantage at the onset of the second half.

PMID- 25048431
TI  - Clinical PD/PDT in North America: An historical review.
AB  - The healing properties of light have been appreciated for thousands of years.
      However, the harnessing of light energy to create a rigorous and reliable means
      to diagnose and treat human disease is only a relatively recent phenomenon.
      Despite outstanding results from ancient history and subsequent reemergence and
      refinement of this knowledge over the last 100 years, it took again the hand of
      serendipity to open the modern age of Photodiagnosis and Photodynamic Therapy.
      Based on the prescience and perseverance of a handful, the under appreciated
      observations of tumor fluorescence and photodynamic action have been brought to a
      worldwide audience. This review highlights the development of clinical
      Photodiagnosis and Photodynamic Therapy, emphasizing the significant events and
      milestones taking place in North America. 

PMID- 25048433
TI  - Spectrometric characteristics and tumor-affinity of a novel photosensitizer: mono
      l-aspartyl aurochlorin e6 (Au-NPe6).
AB  - Photodiagnosis and photodynamic therapy with photosensitizers can be indicated
      only for tumors of the superficial type, because these approaches utilizing
      visible light are limited by said light penetrability. To overcome this
      disadvantage, we innovated a novel photosensitizer, mono-l-aspartyl aurochlorin
      e6 (Au-NPe6), by incorporating a gold atom in the center of tetrapyrrole ring of
      NPe6 with a coordination bond. The gold atom in Au-NPe6 plays a role as an X-ray
      interceptor to detect deeply sited tumors. In this study, the absorption spectrum
      of novel Au-NPe6 in the diagnosis of deeply sited tumors was investigated, and
      the results were compared with the parent photosensitizer NPe6. Furthermore, the
      tumor-affinity of Au-NPe6 was evaluated using atomic absorption spectrometry.
      Despite the fact that both photosensitizers display a difference in the
      absorption spectrum, waveform changes of either photosensitizer with human serum
      albumin established a saturation point at a molar ratio of 1:1. The results
      indicate that it is highly possible that Au-NPe6 bound with albumin at a molar
      ratio (1:1) similar to NPe6. The accumulation rate of gold in tumor tissues was
      always significantly (p<0.05) higher than that in normal muscle tissues during
      the observation terms. Moreover, absorption spectra of tumor-tissue homogenates
      obtained from tumor-bearing mice after Au-NPe6 administration revealed a common
      peak with a wavelength equivalent to that of albumin-bond Au-NPe. This result
      suggests that the gold atom and NPe6 probably remained bonded even when Au-NPe6
      was incorporated in tumor tissues. 

PMID- 25048432
TI  - Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and
      cellular localization.
AB  - The use of non-toxic dyes or photosensitizers (PS) in combination with harmless
      visible light that is known as photodynamic therapy (PDT) has been known for over
      a hundred years, but is only now becoming widely used. Originally developed as a
      tumor therapy, some of its most successful applications are for non-malignant
      disease. In a series of three reviews we will discuss the mechanisms that operate
      in the field of PDT. Part one discusses the recent explosion in discovery and
      chemical synthesis of new PS. Some guidelines on how to choose an ideal PS for a
      particular application are presented. The photochemistry and photophysics of PS
      and the two pathways known as Type I (radicals and reactive oxygen species) and
      Type II (singlet oxygen) photochemical processes are discussed. To carry out PDT
      effectively in vivo, it is necessary to ensure sufficient light reaches all the
      diseased tissue. This involves understanding how light travels within various
      tissues and the relative effects of absorption and scattering. The fact that most
      of the PS are also fluorescent allows various optical imaging and monitoring
      strategies to be combined with PDT. The most important factor governing the
      outcome of PDT is how the PS interacts with cells in the target tissue or tumor,
      and the key aspect of this interaction is the subcellular localization of the PS.
      Examples of PS that localize in mitochondria, lysosomes, endoplasmic reticulum,
      Golgi apparatus and plasma membranes are given. Finally the use of 5
      aminolevulinic acid as a natural precursor of the heme biosynthetic pathway,
      stimulates accumulation of the PS protoporphyrin IX is described. 

PMID- 25048434
TI  - Brain PDD and PDT unlocking the mystery of malignant gliomas.
AB  - Malignant brain tumours (MBTs) have one of the worst outcomes of human cancers
      today and their incidence is on the increase. Current treatment failure is
      usually due to local recurrence of the tumour rather than distant metastasis. In
      the last three decades we have seen many novel and potentially effective
      treatment strategies rise rapidly to the rescue. Sadly, however, the majority of
      these approaches were not good enough to withstand the harsh reality of the
      sceptical gaze of the scientific eye or the stringent health economics of this
      millennium. PDD and PDT, however, is one of the few therapies fighting back and
      still standing today. The results of its randomised controlled trials are eagerly
      awaited. To date the literature suggests that both PDD and PDT significantly
      prolong the time to tumour progression, reduce local recurrence, increase radical
      resection and prolong overall survival of MBTs. PDD and PDT are well tolerated by
      patients and worthwhile pursuing. 

PMID- 25048435
TI  - Photodynamic therapy (PDT) using topically applied delta-aminolevulinic acid
      (ALA) for the treatment of malignant skin tumors.
AB  - BACKGROUND: The objective of our study was to determine therapeutic response to
      photodynamic therapy (PDT) and adverse reaction of PDT in 126 patients with 141
      lesions: 36 patients with 41 lesions of superficial basal cell carcinoma (BCC),
      35 patients with nodular BCC, 42 patients with ulcerated BCC, four patients with
      14 lesions of actinic keratoses, five with superficial squamous cell carcinoma
      (SCC) and four with Bowen's disease. METHODS: Patients with skin malignancies
      were treated using 20% aminolevulinic acid (ALA) (Medac GmbH, Wedel, Germany)
      topically and light from an argon-pumped dye laser. RESULTS: A complete response
      was achieved in 81.5% treated lesions. A partial response after PDT in 10.6%
      treated lesions, no response in 7.8% treated lesions and 11.3% lesions
      recurrences during 10-36 months follow-up were observed. Following light exposure
      skin lesions became necrotic and showed hemorrhagic crusts and the cosmetic
      outcome was excellent or good in 97 of the completely responding lesions (84.3%).
      CONCLUSIONS: Clinical studies reported by other groups have shown similar high
      percentages of clinical cure. PDT appears to be a more feasible alternative to
      conventional therapy of skin malignancies.

PMID- 25048436
TI  - Photodynamic therapy and photodiagnosis for Barrett's oesophagus and early
      oesophageal carcinoma.
AB  - Over the last few decades the there has been a huge increase in the incidence of
      oesophageal adenocarcinoma, surpassing that of any other solid tumour. Barrett's
      oesophagus is recognised as a pre-malignant cursor. Surveillance programmes have
      evolved to monitor Barrett's oesophagus, with the intention to detect early
      malignant transformation. Using photosensitive agents photodiagnosis is
      developing to detect this transformation before it is visible endoscopically to
      allow early treatment. Photodynamic therapy is a non-thermal endoscopic ablative
      technique, which incorporates the same photosensitive agents to treat Barrett's
      oesophagus as well as malignant disease. In this article we review the present
      status of photodiagnosis and photodynamic therapy in the management of Barrett's
      oesophagus and early oesophageal carcinoma. 

PMID- 25048437
TI  - Pharmacokinetic and phototherapeutic studies of monocationic
      methoxyphenylporphyrin derivative.
AB  - BACKGROUND AND OBJETIVE: Photodynamic therapy, a novel treatment for cancer,
      works through photoactivation of a tumor-localized photosensitive drug, and
      localized through oxidative damage to kill cells and ablate tumors.
      Pharmacokinetic and phototherapeutic properties of a cationic porphyrin were
      assayed in a Balb/c mouse cancer model in order to evaluate its efficiency as
      photosensitizer. METHODS: Biodistribution studies were carried out by
      intraperitoneal injection of 5mg/kg CP incorporated into a liposome solution. CP
      was recovered from serum and organs at various times after treatment. The serum
      biochemical parameters and histological studies were used to test hepatic and
      renal functionality. For phototherapeutic studies, the light source used was a
      slide projector (360J/cm(2)). The efficiency of CP was evaluated by following
      tumor growth curves for 10 days after PDT doses. Immunohistochemical detection
      was carried out to evaluate caspase-3 activation in CP-PDT-treated tumors.
      RESULTS AND CONCLUSIONS: The photosensitizer distribution suggests that CP is
      mainly eliminated from the organism via the bile-gut pathway, and that neurotoxic
      and cutaneous photosensitivity effects are reduced or absent. The porphyrin
      distribution from bloodstream to tissue began at 24h of drug administration. CP
      did not affect the hepatic and renal functionality, as was demonstrated by the
      physiological parameters. PDT-treated tumors showed delay in growth rate as
      compared to untreated control mice. Biochemical studies showed that the efficient
      tumor regression is dependent on caspase-3 activity signaling response associated
      with apoptosis. The results obtained suggest that the porphyrin CP may be a
      promising candidate for further use in PDT treatments.

PMID- 25048438
TI  - Treatment of melanoma lesions using methylene blue and RL50 light source.

PMID- 25048439
TI  - Prognostic value of prior history of urothelial carcinoma of the bladder in
      patients with upper urinary tract urothelial carcinoma: results from a
      retrospective multicenter study.
AB  - BACKGROUND: Patients with urothelial carcinoma (UC) often develop multifocal
      metachronous tumors throughout the genitourinary tract. In the present study, we
      evaluated the prognostic value of prior history of UC of the bladder (UCB) in
      patients with upper tract urothelial carcinoma (UTUC) in an international multi
      institutional cohort. PATIENTS AND METHODS: Data from 785 patients who underwent
      radical nephroureterectomy (RNU) with ipsilateral bladder cuff resection at nine
      academic institutions in Europe and the USA between 1987 and 2008 were reviewed.
      Log-rank tests and Cox proportional hazards regression models were used for
      univariable and multivariable analyses. RESULTS: The median follow-up of the
      whole cohort was 34 months (interquartile range 15-66 months). Five hundred and
      fifty-eight (72 %) patients had no UCB before the diagnosis of UTUC; a prior
      history of non-muscle-invasive and muscle-invasive UCB before the UTUC was found
      in 179 (23 %) and 36 (5 %), respectively. History of UCB before RNU was an
      independent predictor of both recurrence-free survival (p = 0.012; no UCB vs. non
      muscle-invasive UCB: hazard ratio (HR) 1.4, p = 0.082; no UCB vs. muscle-invasive
      UCB: HR 2.1, p = 0.007) and cancer-specific survival (p = 0.008; no UCB vs. non
      muscle-invasive UCB: HR 1.2, p = 0.279; no UCB vs. muscle-invasive UCB: HR 2.3, p
      = 0.008) on multivariable Cox regression analyses that included age, gender,
      surgical type, stage, grade, presence of concomitant carcinoma in situ, presence
      of lymphovascular invasion, and lymph node status. CONCLUSIONS: Prior history of
      muscle-invasive UCB was significantly associated with an increased risk of
      disease recurrence and cancer-specific death in patients with UTUC.

PMID- 25048440
TI  - Assessment of oligogalacturonide from citrus pectin as a potential antibacterial
      agent against foodborne pathogens.
AB  - Foodborne diseases are an important public health problem in the world. The
      bacterial resistance against presently used antibiotics is becoming a public
      health issue; hence, the discovery of new antimicrobial agents from natural
      sources attracts a lot of attention. Antibacterial activities of
      oligogalacturonide from commercial microbial pectic enzyme (CPE) treated citrus
      pectin, which exhibits antioxidant and antitumor activities, against 4 foodborne
      pathogens including Salmonella Typhimurium, Staphylococcus aureus, Listeria
      monocytogenes, and Pseudomonas aeruginosa was assessed. Pectin hydrolysates from
      CPE hydrolysis exhibited antibacterial activities. However, no antibacterial
      activity of pectin was observed. Citrus oligogalacturonide from 24-h hydrolysis
      exhibited bactericidal effect against all selected foodborne pathogens and
      displayed minimal inhibitory concentration at 37.5 MUg/mL for P. aeruginosa, L.
      monocytogenes, and S. Typhimurium, and at 150.0 MUg/mL for S. aureus. 

PMID- 25048441
TI  - Incidence, predictors, and temporal trends of sudden cardiac death after heart
      transplantation.
AB  - BACKGROUND: Sudden cardiac death (SCD) has been reported to be a significant mode
      of death after heart transplantation (HT) in small case series. However, the
      incidence, timing, and predictors of SCD have not been examined in a large
      multicenter HT cohort. OBJECTIVE: The purpose of this study was to examine the
      incidence, timing, predictors, and temporal trends of SCD after HT. METHODS:
      Adults (>=18 years) who underwent first-time HT in the United States between 1987
      and 2012 were retrospectively identified from the United Network for Organ
      Sharing (UNOS) registry. Patients with sudden cardiac arrest as the primary cause
      of death constituted the SCD group. RESULTS: Data on 37,492 HT recipients (mean
      age 51.9 +/- 11.7 years, 77% male, 78% Caucasian) were analyzed. During mean
      follow-up of 6.5 +/- 5.7 years, there were 17,324 (46%) deaths, of which 1659
      (9.6%) were SCD. On multivariate Cox regression analysis, left ventricular
      ejection fraction (LVEF) <=40% (hazard ratio [HR] 3.67, 95% confidence interval
      [CI] 3.23-4.17, P < .0001), allograft rejection (HR 1.51, 95% CI 1.35-1.70, P <
      .0001), and donor age (HR 1.17, 95% CI 1.13-1.23, P < .0001) were associated with
      increased risk of SCD, whereas recipient age (HR 0.90, 95% CI 0.86-0.95, P <
      .0001) and Caucasian race (HR 0.61, 95% CI 0.54-0.69, P < .0001) were associated
      with reduced risk. The incidence of SCD has shown no significant temporal
      improvement since 1987 (log-rank P = .84). CONCLUSION: Approximately 10% of
      deaths after HT are due to SCD. Allograft rejection and LVEF <=40% are strong
      predictors of SCD in adult HT patients. Whether implantable cardioverter
      defibrillators would reduce mortality in these patients with a relative higher
      risk of non-SCD remains to be determined.

PMID- 25048442
TI  - Risk predictors of stroke and mortality after ablation for atrial fibrillation:
      the California experience 2005-2009.
AB  - BACKGROUND: Ablation (ABL) is a second-line therapy for the management of atrial
      fibrillation (AF). Single-center studies have demonstrated the safety and
      efficacy of ABL; however, the low event rates render it difficult to assess
      predictors of major adverse events. OBJECTIVE: The purpose of this study was to
      determine the population-based incidence of data and risk factors for both stroke
      <30 days and death after AF ABL. METHODS: Patients (n = 6207) identified as
      having undergone AF ABL between 2005 and 2009 by the California Ambulatory
      Surgery Database in 97 nonfederal hospitals in California were linked to the
      California Patient Discharge Database and to a master death registry. Data from
      these patients were analyzed for primary outcomes of 30-day death and ischemic
      stroke. Independent risk factors for these end-points were determined. RESULTS:
      Mean patient age was 61.9 years, and the majority of the patients were men.
      Thirty-day mortality and stroke after ABL were 0.39% and 0.61%, respectively.
      Independent predictors of death were age >=80 years (odds ratio [OR] 8.2, 95%
      confidence interval [CI] 1.5-43) and heart failure (OR 9.2, 95% CI 3.0-28). Prior
      stroke/transient ischemic attack/stroke was the only independent predictor for
      stroke (OR 6.3, 95% CI 3-13). CONCLUSION: In our large population-based study, we
      found higher procedure-related mortality but comparable stroke rate after AF ABL
      than previously reported. Age >=80 years and heart failure was each independently
      associated with >8-fold increase in odds of death. The only significant predictor
      of stroke was prior stroke/transient ischemic attack. These findings may aid in
      patient selection for AF ABL.

PMID- 25048443
TI  - Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua
      is differentially affected by preterm and term labour and by uterine
      inflammation.
AB  - BACKGROUND: Elucidation of the biochemical pathways involved in activation of
      preterm and term human labour would facilitate the development of effective
      management and inform judgements regarding the necessity for preterm tocolysis
      and post-term induction. Prostaglandins act at all stages of human reproduction,
      and are potentially activators of labour. METHODS: Expression of 15 genes
      involved in prostaglandin synthesis, transport and degradation was measured by
      qPCR using tissue samples from human placenta, amnion and choriodecidua at
      preterm and full-term vaginal and caesarean delivery. Cellular localisation of
      eight prostaglandin pathway proteins was determined by immunohistochemistry.
      RESULTS: Expression of prostaglandin pathway genes was differentially affected by
      factors including gestational age at delivery, and the incidence and duration of
      labour. Chorioamnionitis/deciduitis was associated with upregulation of PTGS2
      (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and
      cyclooxygenase)), along with the inflammatory genes IL8 (interleukin 8), S100A8
      (S100 calcium binding protein A8) and TLR2 (toll-like receptor 2), in amnion and
      choriodecidua, and with downregulation of CBR1 (carbonyl reductase 1) and HPGD
      (hydroxyprostaglandin dehydrogenase 15-(NAD)) in choriodecidua. Protein
      localisation differed greatly between the various maternal and fetal cell types.
      CONCLUSIONS: Preterm and term labour are associated with distinct prostaglandin
      pathway expression profiles; inflammation provokes specific changes, unrelated to
      the presence of labour; spontaneous and induced term labour are
      indistinguishable.

PMID- 25048444
TI  - Ion transport in broad bean leaf mesophyll under saline conditions.
AB  - MAIN CONCLUSION: Salt stress reduces the ability of mesophyll tissue to respond
      to light. Potassium outward rectifying channels are responsible for 84 % of Na
      (+) induced potassium efflux from mesophyll cells. Modulation in ion transport of
      broad bean (Vicia faba L.) mesophyll to light under increased apoplastic salinity
      stress was investigated using vibrating ion-selective microelectrodes (the MIFE
      technique). Increased apoplastic Na(+) significantly affected mesophyll cells
      ability to respond to light by modulating ion transport across their membranes.
      Elevated apoplastic Na(+) also induced a significant K(+) efflux from mesophyll
      tissue. This efflux was mediated predominately by potassium outward rectifying
      channels (84 %) and the remainder of the efflux was through non-selective cation
      channels. NaCl treatment resulted in a reduction in photosystem II efficiency in
      a dose- and time-dependent manner. In particular, reductions in Fv'/Fm' were
      linked to K(+) homeostasis in the mesophyll tissue. Increased apoplastic Na(+)
      concentrations induced vanadate-sensitive net H(+) efflux, presumably mediated by
      the plasma membrane H(+)-ATPase. It is concluded that the observed pump's
      activation is essential for the maintenance of membrane potential and ion
      homeostasis in the cytoplasm of mesophyll under salt stress.

PMID- 25048445
TI  - Identification of small secreted peptides (SSPs) in maize and expression analysis
      of partial SSP genes in reproductive tissues.
AB  - MAIN CONCLUSION: Maize 1,491 small secreted peptides were identified, which were
      classified according to the character of peptide sequences. Partial SSP gene
      expressions in reproductive tissues were determined by qRT-PCR. Small secreted
      peptides (SSPs) are important cell-cell communication messengers in plants. Most
      information on plant SSPs come from Arabidopsis thaliana and Oryza sativa, while
      little is known about the SSPs of other grass species such as maize (Zea mays).
      In this study, we identified 1,491 SSP genes from maize genomic sequences. These
      putative SSP genes were distributed throughout the ten maize chromosomes. Among
      them, 611 SSPs were classified into 198 superfamilies according to their
      conserved domains, and 725 SSPs with four or more cysteines at their C-termini
      shared similar cysteine arrangements with their counterparts in other plant
      species. Moreover, the SSPs requiring post-translational modification, as well as
      defensin-like (DEFL) proteins, were identified. Further, the expression levels of
      110 SSP genes were analyzed in reproductive tissues, including male flower,
      pollen, silk, and ovary. Most of the genes encoding basal-layer antifungal
      peptide-like, small coat proteins-like, thioredoxin-like proteins, gamma-thionins
      like, and DEFL proteins showed high expression levels in the ovary and male
      flower compared with their levels in silk and mature pollen. The rapid
      alkalinization factor-like genes were highly expressed only in the mature ovary
      and mature pollen, and pollen Ole e 1-like genes showed low expression in silk.
      The results of this study provide basic information for further analysis of SSP
      functions in the reproductive process of maize.

PMID- 25048446
TI  - A novel electrochemical DNA biosensor based on HRP-mimicking hemin/G-quadruplex
      wrapped GOx nanocomposites as tag for detection of Escherichia coli O157:H7.
AB  - A novel sensitive electrochemical DNA biosensor was developed for amperometric
      detection of Escherichia coli O157:H7 (E. coli O157:H7). The graphene oxide (GOx)
      was utilized as nanocarrier to immobilize thionine (Thi) and the Au nanoparticles
      coated SiO2 nanocomposites (Au-SiO2) by electrostatic adsorption and the
      adsorption among nanomaterials. Then a large amounts of signal DNA (S2) and G
      quadruplex were immobilized on the GOx-Thi-Au@SiO2 nanocomposites. Finally, hemin
      was intercalated into the G-quadruplex to obtain the hemin/G-quadruplex structure
      as HRP-mimicking DNAzyme. On the basis of the signal amplification strategy of
      GOx-Thi-Au@SiO2 nanocomposites and DNAzyme, the developed DNA biosensor could
      respond to 0.01 nM (S/N=3) with a linear calibration range from 0.02 to 50.0 nM
      E. coli O157:H7, which could be well accepted for early clinical detection. The
      studied system provides new opportunities, and might speed up disease diagnosis,
      treatment and prevention with pathogen.

PMID- 25048447
TI  - 3D origami electrochemical immunodevice for sensitive point-of-care testing based
      on dual-signal amplification strategy.
AB  - A dual signal amplification immunosensing strategy that offers high sensitivity
      and specificity for the detection of low-abundance biomarkers was designed on a
      3D origami electrochemical device. High sensitivity was achieved by using novel
      Au nanorods modified paper working electrode (AuNRs-PWE) as sensor platform and
      metal ion-coated Au/bovine serum albumin (Au/BSA) nanospheres as tracing tags.
      High specificity was further obtained by the simultaneous measurement of two
      cancer markers on AuNRs-PWE surface using different metal ion-coated Au/BSA
      tracers. The metal ions could be detected directly through differential pulse
      voltammetry (DPV) without metal preconcentration, and the distinct voltammetric
      peaks had a close relationship with each sandwich-type immunoreaction. The
      position and size of the peaks reflected the identity and level of the
      corresponding antigen. Integrating the dual-signal amplification strategy, a
      novel 3D origami electrochemical immunodevice for simultaneous detecting
      carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) with linear ranges
      of over 4 orders of magnitude with detection limits down to 0.08 pg mL(-1) and
      0.06 mU mL(-1) was successfully developed. This strategy exhibits high
      sensitivity and specificity with excellent performance in real human serum assay.
      The AuNRs-PWE and the designed tracer on this immunodevice provided a new
      platform for low-cost, high-throughput and multiplex immunoassay and point-of
      care testing in remote regions, developing or developed countries.

PMID- 25048448
TI  - Highly selective and sensitive electrochemical biosensor for ATP based on the
      dual strategy integrating the cofactor-dependent enzymatic ligation reaction with
      self-cleaving DNAzyme-amplified electrochemical detection.
AB  - A dual strategy that combines the adenosine triphosphate (ATP)-dependent
      enzymatic ligation reaction with self-cleaving DNAzyme-amplified electrochemical
      detection is employed to construct the biosensor. In this design, the methylene
      blue-labeled hairpin-structured DNA was self-assembled onto a gold electrode
      surface to prepare the modified electrode through the interaction of Au-S bond.
      In the procedure of ATP-dependent ligation reaction, when the specific cofactor
      ATP was added, the two split oligonucleotide fragments of 8-17 DNAzyme were
      linked by T4 DNA ligase and then released to hybridize with the labeled hairpin
      structured DNA substrate. The linked 8-17 DNAzyme catalyzes the cleavage of the
      hairpin-structured substrate by the addition of Zn(2+), causing the methylene
      blue which contains high electrochemical activity to leave the surface of the
      gold electrode, therefore generating a dramatic decrease of electrochemical
      signal. The decrease of peak current was readily measured by square wave
      voltammetry and a relatively low detection limit (0.05 nM) was obtained with a
      linear response range from 0.1 to 1000 nM. By taking advantage of the highly
      specific cofactor dependence of the DNA ligation reaction, the proposed ligation
      induced DNAzyme cascades demonstrate ultrahigh selectivity toward the target
      cofactor ATP. A catalytic and molecular beacons strategy is further adopted to
      amplify the electrochemical signal detection achieved by cycling and regenerating
      the 8-17 DNAzyme to realize enzymatic multiple turnover, thus one DNAzyme can
      catalyze the cleavage of several hairpin-structured substrates, which improves
      the sensitivity of the newly designed electrochemical sensing system.

PMID- 25048449
TI  - Sensitive and selective detection of thrombin by using a cyclic peptide as
      affinity ligand.
AB  - Here we describe a sensitive assay for thrombin by using a high binding-affinity
      cyclic peptide against thrombin as affinity ligand. The cyclic peptide is
      immobilized on the magnetic beads or microplates to selectively capture thrombin.
      The enriched thrombin then catalyzes the cleavage of a substrate of thrombin to a
      detectable product. The detection of thrombin is finally achieved by measuring
      the generated product. This assay enables the detection of thrombin at tens fM in
      100 uL of sample solution when fluorogenic substrate was applied, while detection
      limits reached pM level when chromogenic substrate was used. Thrombin in plasma
      sample can be detected with this assay. This cyclic peptide affinity ligand shows
      potentials for thrombin analysis in other detection formats.

PMID- 25048450
TI  - A sensitive electrochemical biosensor for detection of protein kinase A activity
      and inhibitors based on Phos-tag and enzymatic signal amplification.
AB  - A simple, highly sensitive and selective electrochemical assay is developed for
      the detection of protein kinase A (PKA) activity based on the specific
      recognition utility of Phos-tag for kinase-induced phosphopeptides and enzymatic
      signal amplification. When the substrate peptide was phosphorylated by PKA
      reaction, they could specifically bind with Phos-tag-biotin in the presence of
      Zn(2+) through the formation of a specific noncovalent complex with the
      phosphomonoester dianion in phosphorylated peptides. Through the further specific
      interaction between biotin and avidin, avidin functionalized horseradish
      peroxidase (HRP) can be captured on the electrode surface. Under the catalytic
      effect of HRP, a sensitive electrochemical signal for benzoquinone was obtained,
      which was related to PKA activity. Under the optimal experiment conditions, the
      proposed electrochemical method presented dynamic range from 0.5 to 25 unit/mL
      with low detection limit of 0.15 unit/mL. This new detection strategy was also
      successfully applied to analyze the inhibition effect of inhibitors (ellagic acid
      and H-89) on PKA activity and monitored the PKA activity in cell lysates.
      Therefore, this Phos-tag-based electrochemical assay offers an alternative
      platform for PKA activity assay and inhibitor screening, and thus it might be a
      valuable tool for development of targeted therapy and clinical diagnosis.

PMID- 25048451
TI  - Measurement properties of the Western Ontario and McMaster Universities
      Osteoarthritis Index: a systematic review.
AB  - OBJECTIVE: To conduct a systematic review of the measurement properties of the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and to
      evaluate the quality of WOMAC measurement studies using COSMIN (Consensus-Based
      Standards for the Selection of Health Measurement Instruments) criteria. METHODS:
      A search was conducted in the MEDLINE, CINAHL, Embase, PsycINFO, Scopus, and
      SPORTDiscus databases through September 2013. Data that assessed the WOMAC
      measurement model, reliability, validity, respondent burden, and equivalence
      across methods of administration were extracted. Overall study quality was rated
      following COSMIN criteria. RESULTS: A total of 76 articles from 22 countries were
      included. Internal consistency reliability was consistently high (>=0.90) for the
      function scale and acceptable (>=0.70) for the pain and stiffness scales. Test
      retest reliability was acceptable. Score equivalence was demonstrated across
      paper and electronic methods of data collection. Floor and ceiling effects were
      low except for notable (24-38%) proportions of patients achieving the best
      possible scores on the pain and stiffness scales 1-23 years after arthroplasty.
      Five exploratory factor analyses did not support a measurement model in which the
      pain and function items were distinct. Correlations between the WOMAC pain and
      function scales were high (median 0.79). The WOMAC pain and function scales had
      similar correlations with other pain measures, and therefore the WOMAC pain scale
      did not show divergent validity. COSMIN criteria were not fully met in most
      studies. CONCLUSION: The WOMAC scales were reliable, but its pain scale was
      highly related to physical function. Further research into joint-specific pain
      measures that have broader content validity is needed.

PMID- 25048453
TI  - Re: Tramadol can selectively manage moderate pain in children following European
      advice limiting codeine use.

PMID- 25048454
TI  - The impact of chelation therapy on survival in transfusional iron overload: a
      meta-analysis of myelodysplastic syndrome.

PMID- 25048455
TI  - Inner-pipe structure to improve column heterogeneity and peak shape.
AB  - Column heterogeneity plays an important role in peak tailing and asymmetric
      profiles. We have designed a novel column structure (concentric column structure)
      that has a concentric inner-pipe nested in a column. This structure was studied
      by a number calculation method and wider diameter column experiments. The results
      showed that column heterogeneity and column efficiency were improved by inner
      pipe structure. Moreover, the results showed that high-efficiency columns were
      stronger influenced by inner-pipe structure than low-efficiency columns. The
      influence of an inner-pipe was related to its size. The optimal inner-pipe
      diameter was nearly 0.625 times of column diameter. By using inner-pipe structure
      in this way, it was possible to decrease column heterogeneity and increase column
      efficiency of a wide-diameter column. 

PMID- 25048457
TI  - Conceptualizing mind, body, spirit interconnections through, and beyond,
      spiritual healing practices.
AB  - CONTEXT: Although research is increasingly exploring the concept of the mind,
      body, spirit (MBS) and its relevance to health and well-being, it remains
      difficult to precisely define it. OBJECTIVE: This research aims to explore
      indigenous and non-indigenous spiritual healers' conceptualizations of MBS and
      consider implications for theory and practice. DESIGN AND SETTING: A total of 12
      spiritual healers from Aotearoa/New Zealand participated in a semi-structured
      interview about their healing practices. INTERVENTION: The research interview
      asked participants to discuss how they conceptualized the mind, body, spirit in
      their work. MAIN OUTCOME MEASURES: The data were analyzed using interpretative
      data analysis. RESULTS: Transcripts of the interviews were analyzed using
      interpretative phenomenological analysis, which led to the identification of
      three major themes: MBS interconnections of healing, impacts on the mind and the
      body, and spiritual aspects of healing. These results are discussed in terms of
      their implications for concepts of healing and conceptualizations of MBS.

PMID- 25048456
TI  - Population structure and distribution patterns of the sibling mosquito species
      Culex pipiens and Culex torrentium (Diptera: Culicidae) reveal different
      evolutionary paths.
AB  - Nowadays a number of endemic mosquito species are known to possess vector
      abilities for various diseases, as e.g. the sibling species Culex pipiens and
      Culex torrentium. Due to their morphological similarity, ecology, distribution
      and vector abilities, knowledge about these species' population structure is
      essential. Culicidae from 25 different sampling sites were collected from March
      till October 2012. All analyses were performed with aligned cox1 sequences with a
      total length of 658 bp. Population structure as well as distribution patterns of
      both species were analysed using molecular methods and different statistical
      tests like distance based redundancy analysis (dbDRA), analysis of molecular
      variances (AMOVA) or McDonald & Kreitman test and Tajima's D. Within both
      species, we could show a genetic variability among the cox1 fragment. The
      construction of haplotype networks revealed one dominating haplotype for Cx.
      pipiens, widely distributed within Germany and a more homogeneous pattern for Cx.
      torrentium. The low genetic differences within Cx. pipiens could be a result of
      an infection with Wolbachia which can induce a sweep through populations by
      passively taking the also maternally inherited mtDNA through the population,
      thereby reducing the mitochondrial diversity as an outcome of reproductive
      incompatibility. Pairwise population genetic differentiation (FST) ranged
      significantly from moderate to very great between populations of Cx. pipiens and
      Cx. torrentium. Analyses of molecular variances revealed for both species that
      the main genetic variability exists within the populations (Cx. pipiens [88.38%];
      Cx. torrentium [66.54%]). Based on a distance based redundancy analysis
      geographical origin explained a small but significant part of the species'
      genetic variation. Overall, the results confirm that Cx. pipiens and Cx.
      torrentium underlie different factors regarding their mitochondrial
      differentiation, which could be a result of endosymbiosis, dispersal between
      nearly located populations or human introduction. 

PMID- 25048458
TI  - Light and pheromone-sensing neurons regulates cold habituation through insulin
      signalling in Caenorhabditis elegans.
AB  - Temperature is a critical environmental stimulus that has a strong impact on an
      organism's biochemistry. Animals can respond to changes in ambient temperature
      through behaviour or altered physiology. However, how animals habituate to
      temperature is poorly understood. The nematode C. elegans stores temperature
      experiences and can induce temperature habituation-linked cold tolerance. Here we
      show that light and pheromone-sensing neurons (ASJ) regulate cold habituation
      through insulin signalling. Calcium imaging reveals that ASJ neurons respond to
      temperature. Cold habituation is abnormal in a mutant with impaired cGMP
      signalling in ASJ neurons. Insulin released from ASJ neurons is received by the
      intestine and neurons regulating gene expression for cold habituation. Thus,
      temperature sensation in a light and pheromone-sensing neuron produces a robust
      effect on insulin signalling that controls experience-dependent temperature
      habituation. 

PMID- 25048459
TI  - An animal model of type A cystinuria due to spontaneous mutation in
      129S2/SvPasCrl mice.
AB  - Cystinuria is an autosomal recessive disease caused by the mutation of either
      SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for
      b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic
      129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones
      that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl
      exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile
      similar to that of patients with cystinuria. In addition, we observed a
      heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of
      cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice,
      129S2/SvPasCrl mice had an increased mortality associated with bilateral
      obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the
      tetrameric transporter of dibasic amino acids was absent in proximal tubules and
      we identified a single pathogenic mutation in a highly conserved region of the
      Slc3a1 gene. This novel mouse model mimicking human disease would allow us
      further pathophysiological studies and may be useful to analyse the
      crystal/tissue interactions in cystinuria. 

PMID- 25048461
TI  - A web-based non-intrusive ambient system to measure and classify activities of
      daily living.
AB  - BACKGROUND: The number of older adults in the global population is increasing.
      This demographic shift leads to an increasing prevalence of age-associated
      disorders, such as Alzheimer's disease and other types of dementia. With the
      progression of the disease, the risk for institutional care increases, which
      contrasts with the desire of most patients to stay in their home environment.
      Despite doctors' and caregivers' awareness of the patient's cognitive status,
      they are often uncertain about its consequences on activities of daily living
      (ADL). To provide effective care, they need to know how patients cope with ADL,
      in particular, the estimation of risks associated with the cognitive decline. The
      occurrence, performance, and duration of different ADL are important indicators
      of functional ability. The patient's ability to cope with these activities is
      traditionally assessed with questionnaires, which has disadvantages (eg, lack of
      reliability and sensitivity). Several groups have proposed sensor-based systems
      to recognize and quantify these activities in the patient's home. Combined with
      Web technology, these systems can inform caregivers about their patients in real
      time (e.g., via smartphone). OBJECTIVE: We hypothesize that a non-intrusive
      system, which does not use body-mounted sensors, video-based imaging, and
      microphone recordings would be better suited for use in dementia patients. Since
      it does not require patient's attention and compliance, such a system might be
      well accepted by patients. We present a passive, Web-based, non-intrusive,
      assistive technology system that recognizes and classifies ADL. METHODS: The
      components of this novel assistive technology system were wireless sensors
      distributed in every room of the participant's home and a central computer unit
      (CCU). The environmental data were acquired for 20 days (per participant) and
      then stored and processed on the CCU. In consultation with medical experts, eight
      ADL were classified. RESULTS: In this study, 10 healthy participants (6 women, 4
      men; mean age 48.8 years; SD 20.0 years; age range 28-79 years) were included.
      For explorative purposes, one female Alzheimer patient (Montreal Cognitive
      Assessment score=23, Timed Up and Go=19.8 seconds, Trail Making Test A=84.3
      seconds, Trail Making Test B=146 seconds) was measured in parallel with the
      healthy subjects. In total, 1317 ADL were performed by the participants, 1211 ADL
      were classified correctly, and 106 ADL were missed. This led to an overall
      sensitivity of 91.27% and a specificity of 92.52%. Each subject performed an
      average of 134.8 ADL (SD 75). CONCLUSIONS: The non-intrusive wireless sensor
      system can acquire environmental data essential for the classification of
      activities of daily living. By analyzing retrieved data, it is possible to
      distinguish and assign data patterns to subjects' specific activities and to
      identify eight different activities in daily living. The Web-based technology
      allows the system to improve care and provides valuable information about the
      patient in real-time.

PMID- 25048462
TI  - Towards active tracking of beating heart motion in the presence of arrhythmia for
      robotic assisted beating heart surgery.
AB  - In robotic assisted beating heart surgery, the control architecture for heart
      motion tracking has stringent requirements in terms of bandwidth of the motion
      that needs to be tracked. In order to achieve sufficient tracking accuracy, feed
      forward control algorithms, which rely on estimations of upcoming heart motion,
      have been proposed in the literature. However, performance of these feed-forward
      motion control algorithms under heart rhythm variations is an important concern.
      In their past work, the authors have demonstrated the effectiveness of a receding
      horizon model predictive control-based algorithm, which used generalized adaptive
      predictors, under constant and slowly varying heart rate conditions. This paper
      extends these studies to the case when the heart motion statistics change
      abruptly and significantly, such as during arrhythmias. A feasibility study is
      carried out to assess the motion tracking capabilities of the adaptive algorithms
      in the occurrence of arrhythmia during beating heart surgery. Specifically, the
      tracking performance of the algorithms is evaluated on prerecorded motion data,
      which is collected in vivo and includes heart rhythm irregularities. The
      algorithms are tested using both simulations and bench experiments on a three
      degree-of-freedom robotic test bed. They are also compared with a position-plus
      derivative controller as well as a receding horizon model predictive controller
      that employs an extended Kalman filter algorithm for predicting future heart
      motion. 

PMID- 25048463
TI  - [Assessing the direct cost of medical care for HIV between the third and tenth
      year of ARV treatment in Dakar].
AB  - The direct cost of medical care for HIV infection-excluding ARVs, viral load and
      CD4 counts-was assessed for patients who received ARV treatment in Senegal within
      the framework of the ANRS cohort 1215, between the third and tenth year of follow
      up. The average annual direct cost was estimated at 120 <euro>/patient/year; this
      amount remained stable over the first ten years of treatment follow-up.
      Biological assessments for routine follow-up account for the majority of these
      costs (66%), followed by drugs (26%). Given the level of economic poverty facing
      by families, patients cannot bear such expenses over several years. However,
      these costs appear low enough to be covered by HIV-treatment programs or included
      in Universal Health Coverage systems. 

PMID- 25048464
TI  - BMP-non-responsive Sca1+ CD73+ CD44+ mouse bone marrow derived osteoprogenitor
      cells respond to combination of VEGF and BMP-6 to display enhanced osteoblastic
      differentiation and ectopic bone formation.
AB  - Clinical trials on fracture repair have challenged the effectiveness of bone
      morphogenetic proteins (BMPs) but suggest that delivery of mesenchymal stem cells
      (MSCs) might be beneficial. It has also been reported that BMPs could not
      increase mineralization in several MSCs populations, which adds ambiguity to the
      use of BMPs. However, an exogenous supply of MSCs combined with vascular
      endothelial growth factor (VEGF) and BMPs is reported to synergistically enhance
      fracture repair in animal models. To elucidate the mechanism of this synergy, we
      investigated the osteoblastic differentiation of cloned mouse bone marrow derived
      MSCs (D1 cells) in vitro in response to human recombinant proteins of VEGF, BMPs
      (-2, -4, -6, -9) and the combination of VEGF with BMP-6 (most potent BMP). We
      further investigated ectopic bone formation induced by MSCs pre-conditioned with
      VEGF, BMP-6 or both. No significant increase in mineralization, phosphorylation
      of Smads 1/5/8 and expression of the ALP, COL1A1 and osterix genes was observed
      upon addition of VEGF or BMPs alone to the cells in culture. The lack of CD105,
      Alk1 and Alk6 expression in D1 cells correlated with poor response to BMPs
      indicating that a greater care in the selection of MSCs is necessary.
      Interestingly, the combination of VEGF and BMP-6 significantly increased the
      expression of ALP, COL1A1 and osterix genes and D1 cells pre-conditioned with
      VEGF and BMP-6 induced greater bone formation in vivo than the non-conditioned
      control cells or the cells pre-conditioned with either VEGF or BMP-6 alone. This
      enhanced bone formation by MSCs correlated with higher CADM1 expression and
      OPG/RANKL ratio in the implants. Thus, combined action of VEGF and BMP on MSCs
      enhances osteoblastic differentiation of MSCs and increases their bone forming
      ability, which cannot be achieved through use of BMPs alone. This strategy can be
      effectively used for bone repair. 

PMID- 25048465
TI  - Catalytic 1,4-rhodium(III) migration enables 1,3-enynes to function as one-carbon
      oxidative annulation partners in C-H functionalizations.
AB  - 1,3-Enynes containing allylic hydrogens cis to the alkyne are shown to act as one
      carbon partners, rather than two-carbon partners, in various rhodium-catalyzed
      oxidative annulations. The mechanism of these unexpected transformations is
      proposed to occur through double C-H activation, involving a hitherto rare
      example of the 1,4-migration of a Rh(III) species. This phenomenon is general
      across a variety of substrates, and provides a diverse range of heterocyclic
      products.

PMID- 25048466
TI  - Haste makes waste: are the data regarding TARGIT-A IORT ready for prime time?

PMID- 25048467
TI  - Molecular features of the basal-like breast cancer subtype based on BRCA1
      mutation status.
AB  - BRCA1-mutated breast cancer is associated with basal-like disease; however, it is
      currently unclear if the presence of a BRCA1 mutation depicts a different entity
      within this subgroup. In this study, we compared the molecular features among
      basal-like tumors with and without BRCA1 mutations. Fourteen patients with BRCA1
      mutated (nine germline and five somatic) tumors and basal-like disease, and 79
      patients with BRCA1 non-mutated tumors and basal-like disease, were identified
      from the cancer genome atlas dataset. The following molecular data types were
      evaluated: global gene expression, selected protein and phospho-protein
      expression, global miRNA expression, global DNA methylation, total number of
      somatic mutations, TP53 and PIK3CA somatic mutations, and global DNA copy-number
      aberrations. For intrinsic subtype identification, we used the PAM50 subtype
      predictor. Within the basal-like disease, we observed minor molecular differences
      in terms of gene, protein, and miRNA expression, and DNA methylation variation,
      according to BRCA1 status (either germinal or somatic). However, there were
      significant differences according to average number of mutations and DNA copy
      number aberrations, and four amplified regions (2q32.2, 3q29, 6p22.3, and
      22q12.2), which are characteristic in high-grade serous ovarian carcinomas, were
      observed in both germline and somatic BRCA1-mutated breast tumors. These results
      suggest that minor, but potentially relevant, baseline molecular features exist
      among basal-like tumors according to BRCA1 status. Additional studies are needed
      to better clarify if BRCA1 genetic status is an independent prognostic feature,
      and more importantly, if BRCA1 mutation status is a predictive biomarker of
      benefit from DNA-damaging agents among basal-like disease. 

PMID- 25048468
TI  - The efficacy and safety of Grafix((r)) for the treatment of chronic diabetic foot
      ulcers: results of a multi-centre, controlled, randomised, blinded, clinical
      trial.
AB  - In a randomised, controlled study, we compared the efficacy of Grafix((r)) , a
      human viable wound matrix (hVWM) (N = 50), to standard wound care (n = 47) to
      heal diabetic foot ulcers (DFUs). The primary endpoint was the proportion of
      patients with complete wound closure by 12 weeks. Secondary endpoints included
      the time to wound closure, adverse events and wound closure in the crossover
      phase. The proportion of patients who achieved complete wound closure was
      significantly higher in patients who received Grafix (62%) compared with controls
      (21%, P = 0.0001). The median time to healing was 42 days in Grafix patients
      compared with 69.5 days in controls (P = 0.019). There were fewer Grafix patients
      with adverse events (44% versus 66%, P = 0.031) and fewer Grafix patients with
      wound-related infections (18% versus 36.2%, P = 0.044). Among the study subjects
      that healed, ulcers remained closed in 82.1% of patients (23 of 28 patients) in
      the Grafix group versus 70% (7 of 10 patients) in the control group (P = 0.419).
      Treatment with Grafix significantly improved DFU healing compared with standard
      wound therapy. Importantly, Grafix also reduced DFU-related complications. The
      results of this well-controlled study showed that Grafix is a safe and more
      effective therapy for treating DFUs than standard wound therapy. 

PMID- 25048469
TI  - Interventions for replacing missing teeth: different types of dental implants.
AB  - BACKGROUND: Dental implants are available in different materials, shapes and with
      different surface characteristics. In particular, numerous implant designs and
      surface modifications have been developed for improving clinical outcome. This is
      an update of a Cochrane review first published in 2002, and previously updated in
      2003, 2005 and 2007. OBJECTIVES: Primary: to compare the clinical effects of
      different root-formed osseointegrated dental implant types for replacing missing
      teeth for the following specific comparisons: implants with different surface
      preparations, but having similar shape and material; implants with different
      shapes, but having similar surface preparation and material; implants made of
      different materials, but having similar surface preparation and shape; different
      implant types differing in surface preparation, shape, material or a combination
      of these.Secondary: to compare turned and roughened dental implants for
      occurrence of early implant failure (before prosthetic loading) and occurrence of
      peri-implantitis. SEARCH METHODS: We searched the following electronic databases:
      the Cochrane Oral Health Group's Trials Register (to 17 January 2014), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2013, Issue 12), MEDLINE via OVID (1946 to 17 January 2014) and EMBASE via OVID
      (1980 to 17 January 2014). We placed no restrictions on the language or date of
      publication when searching the electronic databases. SELECTION CRITERIA: We
      included any randomised controlled trial (RCT) comparing osseointegrated dental
      implants of different materials, shapes and surface properties having a follow-up
      in function of at least one year. Outcome measures were success of the implants,
      radiographic peri-implant marginal bone levels changes and incidence of peri
      implantitis. DATA COLLECTION AND ANALYSIS: At least two review authors
      independently conducted screening, risk of bias assessment and data extraction of
      eligible trials in duplicate. We expressed results using fixed-effect models (if
      up to three studies were present in a meta-analysis) or random-effects models
      (when there were more than three studies) using mean differences (MD) for
      continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95%
      confidence intervals (CI). We reported the following endpoints: one, three, five
      and 10 years after functional loading. MAIN RESULTS: We identified 81 different
      RCTs. We included 27 of these RCTs, reporting results from 1512 participants and
      3230 implants in the review. We compared 38 different implant types with a follow
      up ranging from one to 10 years. All implants were made of commercially pure
      titanium or its alloys, and had different shapes and surface preparations. We
      judged two trials to be at low risk of bias, 10 to be at unclear risk of bias and
      15 to be at high risk of bias. On a 'per participant' rather than 'per implant'
      basis, we found no significant differences between various implant types for
      implant failures. The only observed statistically significant difference for the
      primary objective regarded more peri-implant bone loss at Nobel Speedy Groovy
      implants when compared with NobelActive implants (MD -0.59 mm; 95% CI -0.74 to 
      0.44, different implant shapes). The only observed statistically significant
      difference for the secondary objective was that implants with turned (smoother)
      surfaces had a 20% reduction in risk to be affected by peri-implantitis than
      implants with rough surfaces three years after loading (RR 0.80; 95% CI 0.67 to
      0.96). There was a tendency for implants with turned surfaces to fail early more
      often than implants with roughened surfaces. AUTHORS' CONCLUSIONS: Based on the
      results of the included RCTs, we found no evidence showing that any particular
      type of dental implant had superior long-term success. There was limited evidence
      showing that implants with relatively smooth (turned) surfaces were less prone to
      lose bone due to chronic infection (peri-implantitis) than implants with much
      rougher surfaces (titanium-plasma-sprayed). These findings were based on several
      RCTs, often at high risk of bias, with few participants and relatively short
      follow-up periods.

PMID- 25048470
TI  - Multi-walled carbon nanotube inhibits CA1 glutamatergic synaptic transmission in
      rat's hippocampal slices.
AB  - The purpose of the study was to investigate the neurotoxic effect of multi-walled
      carbon nanotubes (MWCNTs) on the properties of glutamatergic synaptic
      transmission in rat's hippocampal slices using whole-cell patch clamp technique.
      The amplitude and frequency of excitatory postsynaptic current (EPSC) were
      accessed on the hippocampal pyramidal neurons. The alterations of glutamatergic
      synaptic transmission in CA3-CA1 were examined by measuring both the amplitude of
      evoked excitatory postsynaptic current (eEPSC) and paired-pulse ratio (PPR). The
      data showed that the amplitude of either spontaneous excitatory postsynaptic
      current (sEPSC) or miniature excitatory postsynaptic current (mEPSC) was
      significantly inhibited by 1 MUg/mL MWCNTs. However, it was found that there was
      a trend of different change on the frequency index. When 1 MUg/mL MWCNTs was
      applied, there were a decreased frequency of mEPSC and an increased frequency of
      sEPSC, which might be due to the effect of action potential. Furthermore, the
      amplitudes of eEPSC at CA3-CA1 synapses were remarkably decreased. And the mean
      amplitude of AMPAR-mediated eEPSC was significantly reduced as well. Meanwhile, a
      majority of PPRs data were greater than one. There were no significant
      differences of PPRs between control and MWCNTs states, but an increased trend of
      paired-pulse facilitation was found. These results suggested that MWCNT markedly
      inhibited hippocampal CA1 glutamatergic synaptic transmission in vitro, which
      provided new insights into the MWCNT toxicology on CNS at cellular level.

PMID- 25048471
TI  - [LDL cholesterol control in patients with very high cardiovascular risk. A
      simplified algorithm for achieving LDL cholesterol goals "in two steps"].
AB  - Reducing low density lipoprotein-cholesterol (LDL-c) is the main lipid goal of
      treatment for patients with very high cardiovascular risk. In these patients the
      therapeutic goal is to achieve a LDL-c lower than 70 mg/dL, as recommended by the
      guidelines for cardiovascular prevention commonly used in Spain and Europe.
      However, the degree of achieving these objectives in this group of patients is
      very low. This article describes the prevalence of the problem and the causes
      that motivate it. Recommendations and tools that can facilitate the design of an
      optimal treatment strategy for achieving the goals are also given. In addition, a
      new tool with a simple algorithm that can allow these very high risk patients to
      achieve the goals "in two-steps", i.e., with only two doctor check-ups, is
      presented.

PMID- 25048473
TI  - Adverse events associated with metal contamination of traditional chinese
      medicines in Korea: a clinical review.
AB  - This study was performed to review studies carried out in Korea reporting toxic
      reactions to traditional Chinese medicines (TCMs) as a result of heavy metal
      contamination. PubMed (1966-August 2013) and International Pharmaceutical
      Abstracts (1965-August 2013) were searched using the medical subject heading
      terms of "Medicine, Chinese Traditional," "Medicine, Korean Traditional,"
      "Medicine, Traditional," "Metals, Heavy," and "Drug Contamination". For Korean
      literature, Korea Med (http://www.koreamed.org), the Korean Medical Database
      (http://kmbase.medric.or.kr), National Discovery for Science Leaders
      (www.ndsl.kr), Research Information Sharing Service (http://www.riss.kr), and
      Google Scholar were searched using the terms "Chinese medicine," "Korean
      medicine," "herbal medicine," and "metallic contamination" in Korean.
      Bibliographies of case reports and case series, identified using secondary
      resources, were also utilized. Only literature describing cases or studies
      performed in Korea were included. Case reports identified clear issues with heavy
      metal, particularly lead, contamination of TCMs utilized in Korea. No
      international standardization guidelines for processing, manufacturing and
      marketing of herbal products exist. Unacceptably high levels of toxic metals can
      be present in TCM preparations. Health care providers and patients should be
      educated on the potential risks associated with TCMs. International advocacy for
      stricter standardization procedures for production of TCMs is warranted. 

PMID- 25048472
TI  - The role of high mobility group box 1 in innate immunity.
AB  - With growing accounts of inflammatory diseases such as sepsis, greater
      understanding the immune system and the mechanisms of cellular immunity have
      become primary objectives in immunology studies. High mobility group box 1
      (HMGB1) is a ubiquitous nuclear protein that is implicated in various aspects of
      the innate immune system as a damage-associated molecular pattern molecule and a
      late mediator of inflammation, as well as in principal cellular processes, such
      as autophagy and apoptosis. HMGB1 functions in the nucleus as a DNA chaperone;
      however, it exhibits cytokine-like activity when secreted by injurious or
      infectious stimuli. Extracellular HMGB1 acts through specific receptors to
      promote activation of the NF-kappaB signaling pathway, leading to production of
      cytokines and chemokines. These findings further implicate HMGB1 in lethal
      inflammatory diseases as a crucial regulator of inflammatory, injurious, and
      infectious responses. In this paper, we summarize the role of HMGB1 in
      inflammatory and non-inflammatory states and assess potential therapeutic
      approaches targeting HMGB1 in inflammatory diseases. 

PMID- 25048474
TI  - Long-term survival analysis of korean breast cancer patients at a single center:
      improving outcome over time.
AB  - PURPOSE: The prognosis of breast cancer has been consistently improving. We
      analyzed our cohort of breast cancer patients with a long-term follow up at a
      single center over time. MATERIALS AND METHODS: A total of 1889 patients with
      known cancer stages were recruited and analyzed between January 1991 and December
      2005. Patients were classified according to the time periods (1991-1995; 1996
      2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human
      epidermal growth receptor-2 status and Ki67 were reported between April 2004 and
      December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years,
      the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On
      multivariate analysis for OS and recurrence-free survival (RFS), the time period
      was demonstrated to be a significant factor independent of conventional
      prognostic markers. In the survival analysis performed for each stage (I to III),
      OS and RFS significantly improved according to the time periods. Adoption of new
      agents in adjuvant chemotherapy and endocrine therapy was increased according to
      the elapsed time. In the patients with known subtypes, OS and RFS significantly
      differed among the subtypes, and the triple-negative subtype showed the worst
      outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with
      a long-term follow up, our data show an improved prognosis over the past decades,
      and harbor the contribution of advances in adjuvant treatment. Moreover, we
      provided new insight regarding comparison of the prognostic impact between the
      tumor burden and subtypes.

PMID- 25048475
TI  - LRIG1 enhances chemosensitivity by modulating BCL-2 expression and receptor
      tyrosine kinase signaling in glioma cells.
AB  - PURPOSE: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) are an
      inhibitor of receptor tyrosine kinases (RTKs) that was discovered in recent
      years, and many studies showed that LRIG1 is a tumor suppressor gene and may be
      related to tumor drug resistance. In this study, we explored whether LRIG1
      protein expression can improve the chemosensitivity of glioma cells and what was
      its mechanism. MATERIALS AND METHODS: We collected 93 cases of glioma tissues and
      detected the expression of LRIG1 and BCL-2. We constructed a multidrug resistance
      cell line U251/multidrug resistance (MDR) and examined the change of LRIG1 and
      BCL-2 at mRNA and protein expression levels. LRIG1 expression was upregulated in
      U251/MDR cells and we detected the change of multidrug resistance. Meanwhile, we
      changed the expression of LRIG1 and BCL-2 and explored the relationship between
      LRIG1 and BCL-2. Finally, we also explored the relationship between LRIG1 and
      RTKs. RESULTS: LRIG1 was negatively correlated with BCL-2 expression in glioma
      tissue and U251/MDR cells, and upregulation of LRIG1 can enhance chemosensitivity
      and inhibit BCL-2 expression. Furthermore, LRIG1 was negatively correlated with
      RTKs in U251/MDR cells. CONCLUSION: These results demonstrated that LRIG1 can
      improve chemosensitivity by modulating BCL-2 expression and RTK signaling in
      glioma cells.

PMID- 25048476
TI  - Overexpression of mucin 13 due to promoter methylation promotes aggressive
      behavior in ovarian cancer cells.
AB  - PURPOSE: Recent discoveries suggest that aberrant DNA methylation provides cancer
      cells with advanced metastatic properties. However, the precise regulatory
      mechanisms controlling metastasis genes and their role in metastatic
      transformation are largely unknown. To address epigenetically-regulated gene
      products involved in ovarian cancer metastasis, we examined the mechanisms
      regulating mucin 13 (MUC13) expression and its influence on aggressive behaviors
      of ovarian malignancies. MATERIALS AND METHODS: We injected SK-OV-3 ovarian
      cancer cells peritoneally into nude mice to mimic human ovarian tumor metastasis.
      Overexpression of MUC13 mRNA was detected in metastatic implants from the
      xenografts by expression microarray analysis and quantitative reverse
      transcription polymerase chain reaction (qRT-PCR). The DNA methylation status
      within the MUC13 promoter region was determined using bisulfite sequencing PCR
      and quantitative methylation-specific PCR. We evaluated the effects of exogenous
      MUC13 on cell invasion and migration using in vitro transwell assays. RESULTS:
      MUC13 mRNA expression was up-regulated, and methylation of specific CpG sites
      within the promoter was reduced in the metastatic implants relative to those in
      wild-type SK-OV-3 cells. Addition of a DNA methyltransferase inhibitor to SK-OV-3
      cells induced MUC13 expression, thereby implying epigenetic regulation of MUC13
      by promoter methylation. MUC13 overexpression increased migration and
      invasiveness, compared to control cells, suggesting aberrant up-regulation of
      MUC13 is strongly associated with progression of aggressive behaviors in ovarian
      cancer. CONCLUSION: We provide novel evidence for epigenetic regulation of MUC13
      in ovarian cancer. We suggest that the DNA methylation status within the MUC13
      promoter region may be a potential biomarker of aggressive behavior in ovarian
      cancer.

PMID- 25048477
TI  - Prognostic value of sex-hormone receptor expression in non-muscle-invasive
      bladder cancer.
AB  - PURPOSE: We investigated sex-hormone receptor expression as predicting factor of
      recurrence and progression in patients with non-muscle invasive bladder cancer.
      MATERIALS AND METHODS: We retrospectively evaluated tumor specimens from patients
      treated for transitional cell carcinoma of the bladder at our institution between
      January 2006 and January 2011. Performing immunohistochemistry using a monoclonal
      androgen receptor antibody and monoclonal estrogen receptor-beta antibody on
      paraffin-embedded tissue sections, we assessed the relationship of
      immunohistochemistry results and prognostic factors such as recurrence and
      progression. RESULTS: A total of 169 patients with bladder cancer were evaluated
      in this study. Sixty-threepatients had expressed androgen receptors and 52
      patients had estrogen receptor beta. On univariable analysis, androgen receptor
      expression was significant lower in recurrence rates (p=0.001), and estrogen
      receptor beta expression was significant higher in progression rates (p=0.004).
      On multivariable analysis, significant association was found between androgen
      receptor expression and lower recurrence rates (hazard ratio=0.500; 95%
      confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta
      expression was not significantly associated with progression rates. CONCLUSION:
      We concluded that the possibility of recurrence was low when the androgen
      receptor was expressed in the bladder cancer specimen and it could be the
      predicting factor of the stage, number of tumors, carcinoma in situ lesion and
      recurrence.

PMID- 25048478
TI  - Surgical outcomes of robotic radical hysterectomy using three robotic arms versus
      conventional multiport laparoscopy in patients with cervical cancer.
AB  - PURPOSE: To compare surgical outcomes of robotic radical hysterectomy (RRH) using
      3 robotic arms with those of conventional laparoscopy in patients with early
      cervical cancer. MATERIALS AND METHODS: A retrospective cohort study included 102
      patients with stage 1A1-IIA2 cervical carcinoma, of whom 60 underwent robotic and
      42 underwent laparoscopic radical hysterectomy (LRH) with pelvic lymph node
      dissection performed between December 2009 and May 2013. Perioperative outcomes
      were compared between two surgical groups. RESULTS: Robotic approach consisted of
      3 robotic arms including the camera arm and 1 conventional assistant port.
      Laparoscopic approach consisted of four trocar insertions with conventional
      instruments. There were no conversions to laparotomy. Mean age, body mass index,
      tumor size, cell type, and clinical stage were not significantly different
      between two cohorts. RRH showed favorable outcomes over LRH in terms of estimated
      blood loss (100 mL vs. 145 mL, p=0.037), early postoperative complication rates
      (16.7% vs. 30.9%, p=0.028), and postoperative complications necessitating
      intervention by Clavien-Dindo classification. Total operative time (200.5+/-61.1
      minutes vs. 215.6+/-83.1 minutes, p=0.319), mean number of lymph node yield
      (23.3+/-9.3 vs. 21.7+/-9.8, p=0.248), and median length of postoperative hospital
      stay (11 days vs. 10 days, p=0.129) were comparable between robotic and
      laparoscopic group, respectively. The median follow-up time was 44 months with 2
      recurrences in the robotic and 3 in the laparoscopic cohort. CONCLUSION: Surgical
      outcomes of RRH and pelvic lymphadenectomy were comparable to that of
      laparoscopic approach, with significantly less blood loss and early postoperative
      complications.

PMID- 25048479
TI  - The added value of double dose gadolinium enhanced 3D T2 fluid-attenuated
      inversion recovery for evaluating small brain metastases.
AB  - PURPOSE: Single dose gadolinium (Gd) enhanced fluid-attenuated inversion recovery
      (FLAIR) is helpful for visualizing superficial parenchymal metastases. However,
      the usefulness of FLAIR with a higher dose of Gd is uncertain. The aim of our
      study was two-folds: first, to prove that the signal to noise ratio (SNR) of
      small brain metastases is higher than large brain metastases on double-dose (DD)
      enhanced FLAIR and, second, to explore the added value of DD Gd enhanced FLAIR in
      relation to T1 GRE for evaluating small brain metastases. MATERIALS AND METHODS:
      For the first purpose, 50 pairs of small (2 mm<diameter<=5 mm) and large brain
      metastases (diameter>5 mm) were included. The difference in the SNR and contrast
      ratio (CR) between small and large metastases on DD Gd-enhanced 3D T2 FLAIR was
      compared by Wilcoxon signed-rank tests. For the second purpose, a total of 404
      small metastases were included. The diagnostic sensitivities between 3D T1
      gradient echo (GRE) alone and combined results of 3D T1 GRE and 3D T2 FLAIR were
      compared with McNemar test. RESULTS: The SNR and CR of small brain metastases
      were significantly higher than those of large brain metastases (p<0.001). In
      qualitative analysis, the diagnostic sensitivities for small brain metastases
      were significantly higher for 3D T1 GRE plus 3D T2 FLAIR than 3D T1 GRE alone
      regardless of scan time (p<0.001). CONCLUSION: Small brain metastases showed
      higher signal intensity than large brain metastases on the DD Gd enhanced 3D T2
      FLAIR images. DD Gd enhanced 3D T2 FLAIR imaging may have a complementary role to
      3D T1 GRE for evaluating small brain metastases.

PMID- 25048480
TI  - Safety and efficacy of switching anticoagulation to aspirin three months after
      successful radiofrequency catheter ablation of atrial fibrillation.
AB  - PURPOSE: Although current guidelines recommend continuing the same antithrombotic
      strategy regardless of rhythm control after radiofrequency catheter ablation
      (RFCA) of atrial fibrillation (AF), anticoagulation has a risk of major bleeding.
      We evaluated the safety of switching warfarin to aspirin in patients with
      successful AF ablation. MATERIALS AND METHODS: Among 721 patients who underwent
      RFCA of AF, 608 patients (age, 57.3+/-10.9 years; 77.0% male, 75.5% paroxysmal
      AF) who had no evidence of AF recurrence at 3 months post-RFCA were included. We
      compared the thromboembolic and hemorrhagic events in patients for whom warfarin
      was switched to aspirin (ASA group; n=296) and patients who were kept on warfarin
      therapy (W group; n=312). RESULTS: There were no significant differences in
      CHA2DS2-VASc or HAS-BLED scores between the groups. In 30 patients in the ASA
      group and 37 patients in W group, AF recurred and warfarin was restarted or
      maintained during the 18.0+/-12.2 months of follow-up. There were no significant
      differences in thromboembolic (0.3% vs. 1.0%, p=0.342) and major bleeding
      incidences (0.7% vs. 0.6%, p=0.958) between ASA and W groups during the follow-up
      period. In the 259 patients with a CHA2DS2-VASc score>=2, there were no
      significant differences in thromboembolism (0.8% and 2.2%, p=0.380) or major
      bleeding incidences (0.8% and 1.4%, p=0.640) between ASA and W groups.
      CONCLUSION: Switching warfarin to aspirin 3 months after successful RFCA of AF
      could be as safe and efficacious as long-term anticoagulation even in patients
      with CHA2DS2-VASc score>=2. However, strict rhythm monitoring cannot be
      overemphasized.

PMID- 25048481
TI  - Multidisciplinary team approach for identifying potential candidate for
      transcatheter aortic valve implantation.
AB  - PURPOSE: We sought to evaluate the clinical usefulness of decision making by a
      multidisciplinary heart team for identifying potential candidates for
      transcatheter aortic valve implantation (TAVI) in patients with symptomatic
      severe aortic stenosis. MATERIALS AND METHODS: The multidisciplinary team
      consisted of two interventional cardiologists, two cardiovascular surgeons, one
      cardiac imaging specialist, and two cardiac anesthesiologists. RESULTS: Out of 60
      patients who were screened as potential TAVI candidates, 31 patients were
      initially recommended as appropriate for TAVI, and 20 of these 31 eventually
      underwent TAVI. Twenty-two patients underwent surgical aortic valve replacement
      (AVR), and 17 patients received only medical treatment. Patients who underwent
      TAVI and medical therapy were older than those who underwent surgical AVR
      (p<0.001). The logistic Euroscore was significantly highest in the TAVI group and
      lowest in the surgical AVR group (p=0.012). Most patients in the TAVI group (90%)
      and the surgical AVR group (91%) had severe cardiac symptoms, but only 47% in the
      medical therapy group had severe symptoms. The cumulative percentages of survival
      without re-hospitalization or all-cause death at 6 months for the surgical AVR,
      TAVI, and medical therapy groups were 84%, 75%, and 28%, respectively (p=0.007,
      by log-rank). CONCLUSION: TAVI was recommended in half of the potential
      candidates following a multidisciplinary team approach and was eventually
      performed in one-third of these patients. One-third of the patients who were
      initially considered potential candidates received surgical AVR with favorable
      clinical outcomes.

PMID- 25048482
TI  - Surgical experience with infective endocarditis and aortic root abscess.
AB  - PURPOSE: This study was conducted to evaluate the surgical outcomes of active
      infective endocarditis with aortic root abscess formation. MATERIALS AND METHODS:
      Between February 1999 and June 2012, 49 patients underwent surgery for active
      endocarditis with aortic root abscess. The infected valve was native in 29
      patients and prosthetic in 20 patients. The patients' mean age was 50+/-14 years,
      and 36 patients were male. Surgery was urgent/emergent in 15 patients (31%). The
      abscess involved the aortic annulus (11), left ventricular outflow tract (18),
      fibrous trigone (16), and mitral annulus (4). In all patients, wide debridement
      of abscess and aortic valve replacement with or without patch reconstruction of
      aortic root or annulus was performed. RESULTS: There were 6 (12%) operative
      deaths. Causes of early mortality were sepsis (2) and multi-organ failure (4). On
      postoperative echocardiogram, there was significant improvement of left
      ventricular dimension (LVEDD, from 58.8+/-11.8 mm to 52.6+/-8.2 mm, p<0.001);
      however, LV ejection fraction was significantly decreased (from 61.4+/-12.0% to
      49.8+/-16.5%, p<0.001). The mean follow-up duration was 68.7+/-40.4 months. There
      was no late death or recurrent endocarditis during follow up. New York Heart
      Association functional class significantly improved from 3.2+/-0.7 to 1.2+/-0.4
      (p<0.001). Kaplan-Meier estimated survival at 10 years was 87.2%. CONCLUSION:
      Surgical treatment for active endocarditis with aortic root abscess is still
      challenging, and was associated with high operative mortality. Nevertheless, long
      term survival was excellent with good functional capacity after recovery from the
      early postoperative period.

PMID- 25048483
TI  - Clinical outcomes of initial dexamethasone treatment combined with a single high
      dose of intravenous immunoglobulin for primary treatment of Kawasaki disease.
AB  - PURPOSE: To investigate the clinical effects of a single high dose intravenous
      immunoglobulin (IVIG) combined with initial dexamethasone as a primary treatment
      on Kawasaki disease (KD). MATERIALS AND METHODS: Between January 2008 and
      December 2010, we reviewed the medical records of 216 patients with complete KD
      patients that were admitted to a single medical center. 106 patients were treated
      with a single high dose of IVIG (2 g/kg) alone and 110 patients received IVIG and
      dexamethasone (0.3 mg/kg per day for three days). RESULTS: The combined IVIG plus
      dexamethasone patient group had a significantly shorter febrile period and
      duration of hospital stay (1.4+/-0.7 days vs. 2.0+/-1.2 days, p<0.001; 5.8+/-1.7
      days vs. 6.9+/-2.5 days, p<0.001, respectively) than the IVIG alone group. The
      combined IVIG plus dexamethasone group required IVIG retreatment significantly
      less than the IVIG only group (12.7% vs. 32%, p=0.003). After completion of the
      initial IVIG, C-reactive protein levels in the combined IVIG plus dexamethasone
      group were significantly lower than those in the IVIG only group (2.7+/-4.0 mg/dL
      vs. 4.6+/-8.7 mg/dL, p=0.03). In the combined IVIG plus dexamethasone group, the
      incidence of coronary artery lesions tended to be lower without worse outcomes at
      admission after initial infusion of IVIG and in follow-up at two months; however,
      the differences were not significant (8.2% vs. 11.3%, p=0.22; 0.9% vs. 2.8%,
      p=0.29). CONCLUSION: Initial combined therapy with dexamethasone and a single
      high-dose of IVIG resulted in an improved clinical course, in particular a
      shorter febrile period, less IVIG retreatment, and shorter hospital stay without
      worse coronary outcomes.

PMID- 25048484
TI  - The efficacy of endoscopic palliation of obstructive jaundice in hepatocellular
      carcinoma.
AB  - PURPOSE: Obstructive jaundice in patients with hepatocellular carcinoma (HCC) is
      uncommon (0.5-13%). Unlike other causes of obstructive jaundice, the role of
      endoscopic intervention in obstructive jaundice complicated by HCC has not been
      clearly defined. The aim of this study was to evaluate the clinical
      characteristics of obstructive jaundice caused by HCC and predictive factors for
      successful endoscopic intervention. MATERIALS AND METHODS: From 1999 to 2009, 54
      patients with HCC who underwent endoscopic intervention to relieve obstructive
      jaundice were included. We defined endoscopic intervention as a clinical success
      when the obstructive jaundice was relieved within 4 weeks. RESULTS: Clinical
      success was achieved in 23 patients (42.6%). Patients in the clinical success
      group showed better Child-Pugh liver function (C-P grade A or B/C; 17/6 vs.
      8/20), lower total bilirubin levels (8.1+/-5.3 mg/dL vs. 23.1+/-10.4 mg/dL) prior
      to the treatment, and no history of alcohol consumption. The only factor
      predictive of clinical success by multivariate analysis was low total bilirubin
      level at the time of endoscopic intervention, regardless of history of alcohol
      consumption [odds ratio 1.223 (95% confidence interval, 1.071-1.396), p=0.003].
      The cut-off value of pre-endoscopic treatment total bilirubin level was 12.8
      mg/dL for predicting the clinical prognosis. Median survival after endoscopic
      intervention in the clinical success group was notably longer than that in the
      clinical failure group (5.6 months vs. 1.5 months, p<=0.001). CONCLUSION: Before
      endoscopic intervention, liver function, especially total bilirubin level, should
      be checked to achieve the best clinical outcome. Endoscopic intervention can be
      helpful to relieve jaundice in well selected patients with HCC.

PMID- 25048485
TI  - The impact of mechanical bowel preparation in elective colorectal surgery: a
      propensity score matching analysis.
AB  - PURPOSE: To evaluate the influence of preoperative mechanical bowel preparation
      (MBP) based on the occurrence of anastomosis leakage, surgical site infection
      (SSI), and severity of surgical complication when performing elective colorectal
      surgery. MATERIALS AND METHODS: MBP and non-MBP patients were matched using
      propensity score. The outcomes were evaluated according to tumor location such as
      right- (n=84) and left-sided colon (n=50) and rectum (n=100). In the non-MBP
      group, patients with right-sided colon cancer did not receive any preparation,
      and patients with both left-sided colon and rectal cancers were given one rectal
      enema before surgery. RESULTS: In the right-sided colon surgery, there was no
      anastomosis leakage. SSI occurred in 2 (4.8%) and 4 patients (9.5%) in the non
      MBP and MBP groups, respectively. In the left-sided colon cancer surgery, there
      was one anastomosis leakage (4.0%) in each group. SSI occurred in none in the
      rectal enema group and in 2 patients (8.0%) in the MBP group. In the rectal
      cancer surgery, there were 5 anastomosis leakages (10.0%) in the rectal enema
      group and 2 (4.0%) in the MBP group. SSI occurred in 3 patients (6.0%) in each
      groups. Severe surgical complications (Grade III, IV, or V) based on Dindo
      Clavien classification, occurred in 7 patients (14.0%) in the rectal enema group
      and 1 patient (2.0%) in the MBP group (p=0.03). CONCLUSION: Right- and left-sided
      colon cancer surgery can be performed safely without MBP. In rectal cancer
      surgery, rectal enema only before surgery seems to be dangerous because of the
      higher rate of severe postoperative complications.

PMID- 25048486
TI  - Child-Pugh score is an independent risk factor for immediate bleeding after
      colonoscopic polypectomy in liver cirrhosis.
AB  - PURPOSE: Post-polypectomy bleeding is the most common colonoscopic polypectomy
      complication. However, the risk of post-polypectomy bleeding in liver cirrhosis
      is unknown. We aimed to evaluate the risk of post-polypectomy bleeding in
      patients with liver cirrhosis. MATERIALS AND METHODS: We included 89 patients
      with liver cirrhosis who received colonoscopic polypectomy between January 2006
      and October 2012. Three hundred forty-eight subjects without liver disease who
      underwent colonoscopic polypectomy comprised the control group. Risks of post
      polypectomy bleeding were analyzed according to patient- and polyp-related
      factors. RESULTS: Among 89 patients, 75 (84.3%) were Child-Pugh class A, 10
      (11.2%) were class B, and 4 (4.5%) were class C. Incidence of immediate post
      polypectomy bleeding was significantly increased in cirrhosis with Child-Pugh
      class B or C compared to liver cirrhosis with Child-Pugh class A or control group
      [hazard ratio (HR) 3.5; p<0.001]. Polyp size (HR 3.6; p=0.032) and pedunculated
      polyps (HR 2.4; p=0.022) were also significant risk factors for immediate post
      polypectomy bleeding in multivariate analysis. CONCLUSION: Cirrhotic patients
      with Child-Pugh class B or C have a high risk of immediate post-polypectomy
      bleeding. Thus, endoscopists should be cautious about performing colonoscopic
      polypectomy in patients with Child-Pugh class B or C.

PMID- 25048487
TI  - Monitoring thiopurine metabolites in korean pediatric patients with inflammatory
      bowel disease.
AB  - PURPOSE: This study aimed to assess the role of thiopurine S-methyltransferase
      (TPMT) and 6-thioguanine nucleotide (6-TGN) as predictors of clinical response
      and side effects to azathioprine (AZA), and estimate the optimal AZA dose in
      Korean pediatric inflammatory bowel disease (IBD) patients. MATERIALS AND
      METHODS: One hundred and nine pediatric IBD patients in whom AZA treatment was
      required were enrolled. Thiopurine metabolites were monitored since September
      2010. Among them, 83 patients who had prescribed AZA for at least 3 months prior
      to September 2010 were enrolled and followed until October 2011 to evaluate
      optimal AZA dose, adverse effects and disease activity before and after
      thiopurine metabolite monitoring. RESULTS: The result of the TPMT genotype was
      that 102 patients were *1/*1 (wild type), four were *1/*3C, one was *1/*6, one
      was *1/*16 (heterozygote) and one was *3C/*3C (homozygote). Adverse effects
      happened in 31 patients pre-metabolite monitoring and in only nine patients post
      metabolite monitoring. AZA dose was 1.4+/-0.31 mg/kg/day before monitoring and
      1.1+/-0.46 mg/kg/day after monitoring (p<0.001). However, there were no
      statistical differences in disease activity during metabolite monitoring period
      (p=0.34). Adverse effects noticeably decreased although reduction of the AZA dose
      since monitoring. CONCLUSION: TPMT genotype and thiopurine metabolite monitoring
      could be helpful to examine TPMT genotypes before administering AZA and to
      measure 6-TGN concentrations during prescribing AZA in IBD patients.

PMID- 25048488
TI  - The association of heart rate variability with parkinsonian motor symptom
      duration.
AB  - PURPOSE: Impaired cardiovascular autonomic regulation is a non-motor symptom of
      Parkinson's disease (PD) and may increase long-term morbidity. This study applied
      frequency-domain analysis of heart rate variability (HRV) to understand the
      progression of sympathetic and parasympathetic cardiac regulation in patients
      with PD. MATERIALS AND METHODS: In this cross-sectional study, 21 male and 11
      female Taiwanese patients with advanced PD and 32 healthy gender- and age-matched
      subjects were enrolled. To minimize artifacts due to subject motion, daytime
      electrocardiograms for 5 minutes were recorded in awake patients during levodopa
      on periods and controls. Using fast Fourier transformation, heart rate variables
      were quantified into a high-frequency power component [0.15-0.45 Hz, considered
      to reflect vagal (parasympathetic) regulation], low-frequency power component
      (0.04-0.15 Hz, reflecting mixed sympathetic and parasympathetic regulation), and
      low-frequency power in normalized units (reflecting sympathetic regulation). The
      significance of between-group differences was analyzed using the paired t-test.
      Pearson correlation analysis and stepwise regression analysis were applied to
      assess the correlation of patient age, PD duration, and disease severity
      (represented by the Unified Parkinson's Disease Rating Scale) with each heart
      rate variables. RESULTS: Impaired HRV is significantly correlated with the
      duration of PD, but not with disease severity and patient age. Meanwhile,
      parasympathetic heart rate variable is more likely than sympathetic heart rate
      variable to be affected by PD. CONCLUSION: PD is more likely to affect cardiac
      parasympathetic regulation than sympathetic regulation by time and the heart rate
      variables have the association with Parkinsonian motor symptom duration.

PMID- 25048489
TI  - Clinical use of diffusion tensor image-merged functional neuronavigation for
      brain tumor surgeries: review of preoperative, intraoperative, and postoperative
      data for 123 cases.
AB  - PURPOSE: To achieve maximal safe resection during brain tumor surgery, functional
      image-merged neuronavigation is widely used. We retrospectively reviewed our
      cases in which diffusion tensor image (DTI)-merged functional neuronavigation was
      performed during surgery. MATERIALS AND METHODS: Between November 2008 and May
      2010, 123 patients underwent surgery utilizing DTI-merged neuronavigation.
      Anatomical magnetic resonance images (MRI) were obtained preoperatively and fused
      with DTI of major white matter tracts, such as the corticospinal tract, optic
      radiation, or arcuate fasciculus. We used this fused image for functional
      neuronavigation during brain tumor surgery of eloquent areas. We checked the DTI
      images together with postoperative MRI images and evaluated the integrity of
      white matter tracts. RESULTS: A single white matter tract was inspected in 78
      patients, and two or more white matter tracts were checked in 45 patients. Among
      the 123 patients, a grossly total resection was achieved in 90 patients (73.2%),
      subtotal resection in 29 patients (23.6%), and partial resection in 4 patients
      (3.3%). Postoperative neurologic outcomes, compared with preoperative function,
      included the following: 100 patients (81.3%) displayed improvement of neurologic
      symptoms or no change, 7 patients (5.7%) experienced postoperative permanent
      neurologic deterioration (additional or aggravated neurologic symptoms), and 16
      patients (13.0%) demonstrated transient worsening. CONCLUSION: DTI-merged
      functional neuronavigation could be a useful tool in brain tumor surgery for
      maximal safe resection. However, there are still limitations, including white
      matter tract shift, during surgery and in DTI itself. Further studies should be
      conducted to overcome these limitations.

PMID- 25048490
TI  - Neck circumference and lowest oxygen saturation are independently associated with
      high coexistence of hypertension in obstructive sleep apnea.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is considered an independent risk factor
      for hypertension. However, it is still not clear which clinical factors are
      related with the presence of hypertension in OSA patients. We aimed to find
      different physical features and compare the sleep study results which are
      associated with the occurrence of hypertension in OSA patients. MATERIALS AND
      METHODS: Medical records were retrospectively reviewed for patients diagnosed
      with OSA at Severance Cardiovascular Hospital between 2010 and 2013. Males with
      moderate to severe OSA patients were enrolled in this study. Clinical and
      polysomnographic features were evaluated to assess clinical variables that are
      significantly associated with hypertension by statistical analysis. RESULTS:
      Among men with moderate to severe OSA, age was negatively correlated with
      hypertension (odds ratio=0.956), while neck circumference was positively
      correlated with the presence of hypertension (odds ratio=1.363). Among the
      polysomnographic results, the lowest O2 saturation during sleep was significantly
      associated with the presence of hypertension (odds ratio=0.900). CONCLUSION: Age
      and neck circumference should be considered as clinically significant features,
      and the lowest blood O2 saturation during sleep should be emphasized in
      predicting the coexistence or development of hypertension in OSA patients.

PMID- 25048491
TI  - Relationship of vitamin D binding protein polymorphisms and lung function in
      Korean chronic obstructive pulmonary disease.
AB  - PURPOSE: Multiple genetic factors are associated with chronic obstructive
      pulmonary disease (COPD). The association of gene encoding vitamin D binding
      protein (VDBP, GC) with COPD has been controversial. We sought to investigate the
      types of GC variants in the Korean population and determine the association of GC
      variants with COPD and lung function in the Korean population. MATERIALS AND
      METHODS: The study cohort consisted of 203 COPD patients and 157 control
      subjects. GC variants were genotyped by the restriction fragment-length
      polymorphism method. Repeated measures of lung function data were analyzed using
      a linear mixed model including sex, age, height, and pack-years of smoking to
      investigate the association of GC genetic factors and lung function. RESULTS:
      GC1F variant was most frequently observed in COPD (46.1%) and controls (42.0%).
      GC1S variant (29.0% vs. 21.4%; p=0.020) and genotype 1S-1S (8.3% vs. 3.4%;
      p=0.047) were more commonly detected in control than COPD. According to linear
      mixed model analysis including controls and COPD, subjects with genotype 1S-1S
      had 0.427 L higher forced expiratory volume in 1 second (FEV1) than those with
      other genotypes (p=0.029). However, interaction between the genotype and smoking
      pack-year was found to be particularly significant among subjects with genotype
      1S-1S; FEV1 decreased by 0.014 L per smoking pack-year (p=0.001). CONCLUSION:
      This study suggested that GC polymorphism might be associated with lung function
      and risk of COPD in Korean population. GC1S variant and genotype 1S-1S were more
      frequently observed in control than in COPD. Moreover, GC1S variant was more
      common in non-decliners than in rapid decliners among COPD.

PMID- 25048492
TI  - Role of 1,25-dihydroxy vitamin D3 and parathyroid hormone in urinary calcium
      excretion in calcium stone formers.
AB  - PURPOSE: To find out the possible role of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] and
      parathyroid hormone (PTH) as intrinsic factors in urinary calcium stone formers
      (SFs), we investigated their relationship with serum and urinary biochemical
      parameters. MATERIALS AND METHODS: A total of 326 calcium SFs (male: 204, female:
      122) were enrolled and underwent outpatient metabolic evaluations including
      1,25(OH)2D3 and PTH as well as serum and 24-hour urinary biochemical parameters.
      As control, 163 age- and sex-matched (2:1) individuals (non-SFs) who have never
      urinary stone episode were included. RESULTS: 1,25(OH)2D3 level was positively
      correlated with urinary calcium excretion (r=0.347, p<0.001). The hypercalciuric
      group and recurrent SFs had higher serum 1,25(OH)2D3 levels than the
      normocalciuric group (p<0.001) and first SFs (p=0.050). In the adjusted multiple
      linear regression analysis, serum 1,25(OH)2D3 level (beta=0.259, p<0.001) and
      serum PTH level (beta=-0.160, p<0.001) were significantly correlated with urinary
      calcium excretion. The patients in highest tertile of 1,25(OH)2D3 had a more than
      3.1 fold risk of hypercalciuria than those in the lowest tertile (odds
      ratio=3.14, 95% confidence interval: 1.431-6.888, p=0.004). No correlation was
      observed between PTH and 1,25(OH)2D3 (R=0.005, p=0.929) in calcium SFs, while a
      negative correlation was found in controls (R=-0.269, p=0.001). CONCLUSION:
      1,25(OH)2D3 was closely correlated with urinary calcium excretion, and high
      1,25(OH)2D3 levels were detected in the hypercalciuric group and in recurrent
      SFs. However, 1,25(OH)2D3 was not correlated with PTH in calcium SFs. These
      findings suggest that 1,25(OH)2D3 might be important intrinsic factor for altered
      calcium regulation in SFs.

PMID- 25048493
TI  - Histone acetylation level and histone acetyltransferase/deacetylase activity in
      ejaculated sperm from normozoospermic men.
AB  - PURPOSE: The aim of this work was to evaluate nuclear histone acetylation level
      and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in
      ejaculated sperm and their relevance to conventional sperm parameters. MATERIALS
      AND METHODS: Thirty-three normozoospermic men were included in this study. Semen
      samples were processed by swim-up and then immunostained by six acetylation
      antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our
      preliminary study verified the expression of HAT/HDAC1 in mature human sperm.
      From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by
      commercially available kits. Nuclear DNA integrity was also measured by TUNEL
      assay. RESULTS: The levels of six acetylation marks were not related with
      conventional sperm parameters including sperm DNA fragmentation index (DFI) as
      well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT
      activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative
      relationship with HDAC activity (r=-0.51, p<0.01). Strict morphology was
      negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity)
      (r=-0.53, p<0.01). CONCLUSION: Our works demonstrated a significant relationship
      of acetylation-associated enzyme activity and strict morphology or sperm DFI.

PMID- 25048494
TI  - Safety and efficacy of conversion from twice-daily tacrolimus to once-daily
      tacrolimus one month after transplantation: randomized controlled trial in adult
      renal transplantation.
AB  - PURPOSE: The purpose of this study was to compare once-daily tacrolimus with
      twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction.
      MATERIALS AND METHODS: This prospective, randomized, open-label, multicenter
      study was conducted at three institutes. Patients in the investigational group
      were converted from tacrolimus twice daily to the same dose of extended-release
      tacrolimus once daily at 1 month post-transplantation, while patients in the
      control group were maintained on tacrolimus twice daily. The efficacies,
      safeties, and patient satisfaction for the two drugs at 6 months post
      transplantation were compared. RESULTS: Sixty patients were enrolled and
      randomized to the investigational group (28 of 29 patients completed the study)
      or the control group (26 of 31 patients completed the study). At 6 months post
      transplantation, composite efficacy failure rates including the incidences of
      biopsy-confirmed acute rejection in the investigational and control groups were
      0% and 10.7%, respectively; patient survival was 100% in each group. No
      difference in estimated glomerular filtration rate values were observed at 6
      months post-transplantation (p=0.97). The safety and satisfaction profile
      (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable
      with that of twice-daily tacrolimus (p=0.35). CONCLUSION: Conversion from twice
      daily tacrolimus to once-daily tacrolimus one month after transplantation is safe
      and effective.

PMID- 25048495
TI  - Evaluating the utility of rapid point-of-care potassium testing for the early
      identification of hyperkalemia in patients with chronic kidney disease in the
      emergency department.
AB  - PURPOSE: Severe hyperkalemia leads to significant morbidity and mortality if it
      is not immediately recognized and treated. The concentration of potassium (K+) in
      the serum increases along with deteriorating renal function. The use of point-of
      care K+ (POC-K+) in chronic kidney disease (CKD) could reduce the time for an
      accurate diagnosis and treatment, saving lives. We hypothesized that POC-K+ would
      accurately report K+ serum level without significant differences compared to
      reference testing, regardless of the renal function of the patient. MATERIALS AND
      METHODS: The retrospective study was performed between January 2008 and September
      2011 at an urban hospital in Seoul. The screening program using POC was conducted
      as a critical pathway for rapid evaluation and treatment of hyperkalemia since
      2008. When a patient with CKD had at least one warning symptom or sign of
      hyperkalemia, both POC-K+ and routine laboratory tests were simultaneously
      ordered. The reliability of the two assays for serum-creatinine was assessed by
      intra-class correlation coefficient (ICC) analysis using absolute agreement of
      two-way mixed model. RESULTS: High levels of reliability were found between POC
      and the laboratory reference tests for K+ (ICC=0.913, 95% CI 0.903-0.922) and
      between two tests for K+ according to changes in the serum-creatinine levels in
      CKD patients. CONCLUSION: The results of POC-K+ correlate well with values
      obtained from reference laboratory tests and coincide with changes in serum
      creatinine of patients with CKD.

PMID- 25048496
TI  - Regulatory B cells are inversely associated with disease activity in rheumatoid
      arthritis.
AB  - PURPOSE: The function of regulatory B lymphocytes is known to be abnormal in
      inflammatory diseases. However, a recent study indicates that IL-10+ B cells seem
      to be expanded in rheumatoid arthritis (RA). Therefore, the state of IL-10+ B
      cells in the peripheral blood from RA patients and healthy controls were
      investigated. MATERIALS AND METHODS: CD19+ cells in peripheral blood mononuclear
      cells were purified from blood samples of RA patients and age and gender-matched
      healthy controls, and stimulated with CD40 ligand and CpG for 48 hours. Then,
      intracellular IL-10 in CD19+ cells was analyzed using flow cytometry. RESULTS:
      There was no significant difference in the proportion of IL-10+ B cells between
      10 RA patients and 10 healthy controls (RA, 0.300+/-0.07 vs. healthy control
      0.459+/-0.07, p=0.114). The proportion of induced IL-10+ B cells to total B cells
      in RA patients was significantly higher than those in controls (RA, 4.44+/-3.44%
      vs. healthy control 2.44+/-1.64%, p=0.033). However, the proportion of IL-10+ B
      cells to total B cells correlated negatively with disease activity in RA patients
      (r=-0.398, p=0.040). Erythrocyte sedimentation rate or C-reactive protein or
      medication was not associated with the proportion of IL-10+ B cells. CONCLUSION:
      The proportion of induced IL-10+ B cell increased in RA patients compared to
      healthy control, however, negatively correlated with disease activity in RA.

PMID- 25048497
TI  - Analgesic opioid dose is an important indicator of postoperative ileus following
      radical cystectomy with ileal conduit: experience in the robotic surgery era.
AB  - PURPOSE: Postoperative ileus (POI) is common following bowel resection for
      radical cystectomy with ileal conduit (RCIC). We investigated perioperative
      factors associated with prolonged POI following RCIC, with specific focus on
      opioid-based analgesic dosage. MATERIALS AND METHODS: From March 2007 to January
      2013, 78 open RCICs and 26 robot-assisted RCICs performed for bladder carcinoma
      were identified with adjustment for age, gender, American Society of
      Anesthesiologists grade, and body mass index (BMI). Perioperative records
      including operative time, intraoperative fluid excess, estimated blood loss,
      lymph node yield, and opioid analgesic dose were obtained to assess their
      associations with time to passage of flatus, tolerable oral diet, and length of
      hospital stay (LOS). Prior to general anaesthesia, patients received epidural
      patient-controlled analgesia (PCA) consisted of fentanyl with its dose adjusted
      for BMI. Postoperatively, single intravenous injections of tramadol were applied
      according to patient desire. RESULTS: Multivariate analyses revealed cumulative
      dosages of both PCA fentanyl and tramadol injections as independent predictors of
      POI. According to surgical modality, linear regression analyses revealed
      cumulative dosages of PCA fentanyl and tramadol injections to be positively
      associated with time to first passage of flatus, tolerable diet, and LOS in the
      open RCIC group. In the robot-assisted RCIC group, only tramadol dose was
      associated with time to flatus and tolerable diet. Compared to open RCIC, robot
      assisted RCIC yielded shorter days to diet and LOS; however, it failed to shorten
      days to first flatus. CONCLUSION: Reducing opioid-based analgesics shortens the
      duration of POI. The utilization of the robotic system may confer additional
      benefit.

PMID- 25048498
TI  - Clinical experience of weight loss surgery in morbidly obese Korean adolescents.
AB  - PURPOSE: Comprehensive multidisciplinary weight management programs encompassing
      various conservative measures have shown only modest weight loss results in obese
      children and adolescents; therefore, bariatric surgery for this population has
      become a matter of discussion. This study aimed to present our experience with
      and outcomes for laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y
      gastric bypass (LRYGB) in morbidly obese Korean adolescents. MATERIALS AND
      METHODS: The prospectively established database of all patients undergoing
      bariatric surgery at Soonchunhyang University Seoul Hospital, Korea between
      January 2011 and January 2013 was retrospectively reviewed. Adolescents aged 14
      to 20 years were included in the present analyses. RESULTS: Twenty-two
      adolescents underwent bariatric surgery during the study period; 14 underwent LSG
      and 8, LRYGB. Of these, 17 were female and 5 were male. The mean age was 19
      years. Their mean body weight and body mass index (BMI) before surgery were 115
      kg and 40.1 kg/m2. The only postoperative complication was intraluminal bleeding
      in 1 patient, which was managed conservatively. The mean BMI decreased to 29.1
      kg/m2 after a mean follow-up of 10 months. The percent excess weight loss (%EWL)
      at 1, 3, 6, and 12 months postoperatively were 19.6, 39.9, 52.6, and 74.2%,
      respectively. Only 1 patient showed %EWL less than 30% at 12 months after
      surgery. All patients with diabetes and sleep apnea were cured of their disease,
      and other comorbidities also improved or resolved after surgery. CONCLUSION:
      Bariatric surgery leads to significant short-term weight loss along with
      resolution of obesity-related comorbidities in obese children and adolescents.

PMID- 25048499
TI  - Risk factors associated with amputation-free survival in patient with diabetic
      foot ulcers.
AB  - PURPOSE: To determine the 1-year survival rate, 1-year amputation-free survival
      rate and the risk factors of amputation for patients with diabetic foot ulcers.
      MATERIALS AND METHODS: One hundred seventy-three patients with diabetic foot
      ulcers were included in our study. Mean patient age was 67.5 (range, 29 to 87, SD
      +/-11.4) years. 74% of the patients were male. Time from study entry to
      amputation and time to death were evaluated separately as censored event times by
      Kaplan-Meier curves and log-rank tests. A multivariate Cox proportional hazards
      regression analysis was carried out for determining the risk factors of
      amputation. RESULTS: The survival rate and amputation-free survival rate were
      96.5% (n=167), 65.9% (n=114), respectively, over one year study period. Severity
      of ulcer was the strongest significant risk factor of amputation [hazard ratio
      (HR): 7.99; confidence interval (CI): 3.12 to 20.47]. Peripheral artery disease
      was also independent risk factor of amputation (HR: 2.64; CI: 1.52 to 4.59).
      CONCLUSION: In assessing the prognosis of diabetic foot ulcers, clinicians should
      consider the severity of ulcer and presence of peripheral artery disease. Our
      study provides important insights into clinical practice and supplementary
      information for both physicians and patients.

PMID- 25048500
TI  - Progressive change in joint degeneration in patients with knee or hip
      osteoarthritis treated with fentanyl in a randomized trial.
AB  - PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease
      the functional impairment of patients. However, there is a possibility that
      opioids induce analgesia and suppress the physiological pain of OA in patients,
      thereby inducing the progression of OA changes in these patients. The purpose of
      the current study was to investigate the possibility of progressive changes in OA
      among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA
      patients were evaluated in the current prospective, randomized, active-controlled
      study. Patients were randomized 1:1:1 into three parallel treatment groups:
      loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication
      was administered for 12 weeks. Pain scores and progressive OA changes on X-ray
      films were evaluated. RESULTS: Overall, pain relief was obtained by all three
      groups. Most patients did not show progressive OA changes; however, 3 patients in
      the transdermal fentanyl group showed progressive OA changes during the 12 weeks
      of treatment. These 3 patients used significantly higher doses than others in the
      transdermal fentanyl group. Additionally, the average pain score for these 3
      patients was significantly lower than the average pain score for the other
      patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce
      progressive changes in knee or hip OA during a relatively short period, compared
      with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.

PMID- 25048501
TI  - Biomechanical analysis of fusion segment rigidity upon stress at both the fusion
      and adjacent segments: a comparison between unilateral and bilateral pedicle
      screw fixation.
AB  - PURPOSE: The purpose of this study was to investigate the effects of unilateral
      pedicle screw fixation on the fusion segment and the superior adjacent segment
      after one segment lumbar fusion using validated finite element models. MATERIALS
      AND METHODS: Four L3-4 fusion models were simulated according to the extent of
      decompression and the method of pedicle screws fixation in L3-4 lumbar fusion.
      These models included hemi-laminectomy with bilateral pedicle screw fixation in
      the L3-4 segment (BF-HL model), total laminectomy with bilateral pedicle screw
      fixation (BF-TL model), hemi-laminectomy with unilateral pedicle screw fixation
      (UF-HL model), and total laminectomy with unilateral pedicle screw fixation (UF
      TL model). In each scenario, intradiscal pressures, annulus stress, and range of
      motion at the L2-3 and L3-4 segments were analyzed under flexion, extension,
      lateral bending, and torsional moments. RESULTS: Under four pure moments, the
      unilateral fixation leads to a reduction in increment of range of motion at the
      adjacent segment, but larger motions were noted at the fusion segment (L3-4) in
      the unilateral fixation (UF-HL and UF-TL) models when compared to bilateral
      fixation. The maximal von Mises stress showed similar patterns to range of motion
      at both superior adjacent L2-3 segments and fusion segment. CONCLUSION: The
      current study suggests that unilateral pedicle screw fixation seems to be unable
      to afford sufficient biomechanical stability in case of bilateral total
      laminectomy. Conversely, in the case of hemi-laminectomy, unilateral fixation
      could be an alternative option, which also has potential benefit to reduce the
      stress of the adjacent segment.

PMID- 25048502
TI  - Passive skeletal muscle excursion after tendon rupture correlates with increased
      collagen content in muscle.
AB  - PURPOSE: This study was designed to measure time-dependent changes in muscle
      excursion and collagen content after tenotomy, and to analyze the correlation
      between muscle excursion and collagen content in a rabbit model. MATERIALS AND
      METHODS: Twenty-four rabbits underwent tenotomy of the second extensor digitorum
      longus (EDL) muscles on the right legs and were randomly assigned to three groups
      based on the period of time after tenotomy (2, 4, and 6 weeks). The second EDL
      muscles on left legs were used as controls. At each time after tenotomy, passive
      muscle excursion and collagen content, determined by hydroxyproline content, were
      measured bilaterally, and the ratio of each value to the normal one was used.
      RESULTS: The mean ratio of muscle excursion after tenotomy to the value of the
      control decreased in a time-dependent fashion: 92.5% at 2 weeks, 78.6% at 4
      weeks, and 55.1% at 6 weeks. The mean ratio of hydroxyproline content in muscle
      to the value of the control increased in a time-dependent fashion: 119.5% at 2
      weeks, 157.3% at 4 weeks, and 166.6% at 6 weeks. There was a significant negative
      correlation between the ratio of hydroxyproline content in muscle after tenotomy
      to the control values and the ratio of muscle excursion after tenotomy to the
      control values (r=-0.602, p=0.002). CONCLUSION: The decrease in muscle excursion
      seems to correlate with the increase in collagen content in the muscle in a time
      dependent fashion following tenotomy.

PMID- 25048503
TI  - Presence of a nail in the medullary canal; is it enough to prevent femoral neck
      shortening in trochanteric fracture?
AB  - PURPOSE: Presence of a cephalomedullary nail (CMN) in the medullary canal has
      been thought as advantageous in the control of femoral neck shortening (FNS) and
      lag screw sliding in trochanteric fracture compared to extramedullary fixation
      system. However, researches on the factors that influence the degree of FNS after
      cephalomedullary nailing are lacking. MATERIALS AND METHODS: We observed 95
      patients (mean age, 75+/-2.8 years) with trochanteric fractures who were treated
      with a CMN, and evaluated the relationship between FNS and patient factors
      including age, gender, fracture type (AO/OTA), bone mineral density, medullary
      canal diameter, canal occupancy ratio (COR=nail size/canal diameter), and tip
      apex distance using initial, immediate postoperative, and follow-up radiography.
      RESULTS: Univariate regression analyses revealed that the degree of FNS was
      significantly correlated with fracture type (A1 versus A3, p<0.001), medullary
      canal diameter (p<0.001), and COR (p<0.001). Multiple regression analyses
      revealed that FNS was strongly correlated with fracture type (p<0.001) and COR
      (p<0.001). CONCLUSION: Presence of a CMN in the medullary canal could not
      effectively prevent FNS in patients with low COR and in A3 type fracture.

PMID- 25048504
TI  - Architectural changes of the gastrocnemius muscle after botulinum toxin type A
      injection in children with cerebral palsy.
AB  - PURPOSE: This study used ultrasonography (US) to investigate the architectural
      changes in gastrocnemius muscles (GCM) after botulinum toxin injection (BoNT-A)
      in children with cerebral palsy (CP). MATERIALS AND METHODS: Thirteen children
      with CP who received a BoNT-A injection into their GCM to treat equinus were
      recruited (9 males and 4 females). Architectural changes in both the medial and
      lateral heads of the GCM from a total of 20 legs were assessed using B-mode, real
      time US. Muscle thickness (MT), fascicle length (FL), and fascicle angle (FA)
      were measured over the middle of the muscle belly in both a resting and neutral
      ankle position. Measures at 1 and 3 months after the injection were compared with
      baseline data taken before the injection. RESULTS: The mean age of the subjects
      was 5.8 (+/-1.6) years. Spasticity was significantly reduced when measured by
      both the modified Tardieu scale and the modified Ashworth scale at 1 and 3 months
      after injection (p<0.05). The MT and FA of both the medial and lateral heads of
      the GCM were significantly reduced for both neutral and resting ankle positions
      at 1 and 3 months after the injection. The FL of both the medial and lateral
      heads of the GCM were significantly increased in a resting position (p<0.05), but
      not in a neutral position. CONCLUSION: Our results demonstrated muscle
      architectural changes induced by BoNT-A injection. The functional significances
      of these changes were discussed.

PMID- 25048505
TI  - Evaluation of optical quality parameters and ocular aberrations in multifocal
      intraocular lens implanted eyes.
AB  - PURPOSE: We investigated the correlations between optical quality parameters
      obtained from the double-pass system and ocular aberrations obtained from the ray
      tracing aberrometer in multifocal intraocular lens (IOL) implanted eyes.
      MATERIALS AND METHODS: Twenty eyes from 20 patients were enrolled in this study.
      Modulation transfer function cutoff frequency, The Strehl ratio, objective
      scatter index, and objective pseudo-accommodation obtained from the double-pass
      system were compared with root mean square (RMS) total aberration, RMS higher
      order aberration, and spherical aberration obtained from the ray-tracing
      aberrometer. Additionally, parameters of the double-pass system and ray-tracing
      aberrometer were compared with manifested refraction values and subjective visual
      acuity, respectively. RESULTS: There was no statistically significant correlation
      between optical quality parameters obtained from the double-pass system and
      ocular aberrations, except between the Strehl ratio and RMS total aberration (r=
      0.566, p=0.018). No significant correlations were found between the parameters of
      both devices, and manifested refraction values or subjective visual acuity.
      CONCLUSION: Optical quality parameters, especially the Strehl ratio, in
      multifocal IOL implanted eyes were affected by RMS total aberration. Further
      studies based on accurate measurements of ocular aberrations and additional
      optical quality parameters are needed to delineate relationships between optical
      quality parameters and ocular aberrations in multifocal IOL implanted eyes.

PMID- 25048506
TI  - Bispectral index monitoring during anesthesiologist-directed propofol and
      remifentanil sedation for endoscopic submucosal dissection: a prospective
      randomized controlled trial.
AB  - PURPOSE: Endoscopic submucosal dissection (ESD) is a technically difficult and
      lengthy procedure requiring optimal depth of sedation. The bispectral index (BIS)
      monitor is a non-invasive tool that objectively evaluates the depth of sedation.
      The purpose of this prospective randomized controlled trial was to evaluate
      whether BIS guided sedation with propofol and remifentanil could reduce the
      number of patients requiring rescue propofol, and thus reduce the incidence of
      sedation- and/or procedure-related complications. MATERIALS AND METHODS: A total
      of 180 patients who underwent the ESD procedure for gastric adenoma or early
      gastric cancer were randomized to two groups. The control group (n=90) was
      monitored by the Modified Observer's Assessment of Alertness and Sedation scale
      and the BIS group (n=90) was monitored using BIS. The total doses of propofol and
      remifentanil, the need for rescue propofol, and the rates of complications were
      recorded. RESULTS: The number of patients who needed rescue propofol during the
      procedure was significantly higher in the control group than the BIS group (47.8%
      vs. 30.0%, p=0.014). There were no significant differences in the incidence of
      sedation- and/or procedure-related complications. CONCLUSION: BIS-guided propofol
      infusion combined with remifentanil reduced the number of patients requiring
      rescue propofol in ESD procedures. However, this finding did not lead to clinical
      benefits and thus BIS monitoring is of limited use during anesthesiologist
      directed sedation.

PMID- 25048508
TI  - Pre-emptive tramadol could reduce pain after ureteroscopic lithotripsy.
AB  - PURPOSE: Optimal analgesia in ambulatory urology patients still remains a
      challenge. The aim of this study was to examine if the pre-emptive use of
      intravenous tramadol can reduce pain after ureteroscopic lithotripsy in patients
      diagnosed with unilateral ureteral stones. MATERIALS AND METHODS: This
      prospective pilot cohort study included 74 patients diagnosed with unilateral
      ureteral stones who underwent ureteroscopic lithotripsy under general anesthesia
      in the Urology Clinic at the Clinical Center of Serbia from March to June 2012.
      All patients were randomly allocated to two groups: one group (38 patients)
      received intravenous infusion of tramadol 100 mg in 500 mL 0.9%NaCl one hour
      before the procedure, while the other group (36 patients) received 500 mL
      0.9%NaCl at the same time. Visual analogue scale (VAS) scores were recorded once
      prior to surgery and two times after the surgery (1 h and 6 h, respectively). The
      patients were prescribed additional postoperative analgesia (diclofenac 75 mg
      i.m.) when required. Pre-emptive effects of tramadol were assessed measuring pain
      scores, VAS1 and VAS2, intraoperative fentanyl consumption, and postoperative
      analgesic requirement. RESULTS: The average VAS1 score in the tramadol group was
      significantly lower than that in the non-tramadol group. The difference in
      average VAS2 score values between the two groups was not statistically
      significant; however, there were more patients who experienced severe pain in the
      non-tramadol group (p<0.01). The number of patients that required postoperative
      analgesia was not statistically different between the groups. CONCLUSION: Pre
      emptive tramadol did reduce early postoperative pain. The patients who received
      pre-emptive tramadol were less likely to experience severe post-operative pain.

PMID- 25048507
TI  - Incidence and risk factors of postoperative nausea and vomiting in patients with
      fentanyl-based intravenous patient-controlled analgesia and single antiemetic
      prophylaxis.
AB  - PURPOSE: We evaluated the incidence and risk factors of postoperative nausea and
      vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled
      analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type
      3 (5 HT3)-receptor antagonist after the general anesthesia. MATERIALS AND
      METHODS: In this retrospective study, incidence and risk factors for PONV were
      evaluated with fentanyl IV-PCA during postoperative 48 hours after various
      surgeries. RESULTS: Four hundred-forty patients (23%) of 1878 had showed PONV.
      PCA was discontinued temporarily in 268 patients (14%), mostly due to PONV (88%
      of 268 patients). In multivariate analysis, female, non-smoker, history of motion
      sickness or PONV, long duration of anesthesia (>180 min), use of desflurane and
      intraoperative remifentanil infusion were independent risk factors for PONV. If
      one, two, three, four, five, or six of these risk factors were present, the
      incidences of PONV were 18%, 19%, 22%, 31%, 42%, or 50%. Laparoscopic surgery and
      higher dose of fentanyl were not risk factors for PONV. CONCLUSION: Despite
      antiemetic prophylaxis with 5 HT3-receptor antagonist, 23% of patients with
      fentanyl-based IV-PCA after general anesthesia showed PONV. Long duration of
      anesthesia and use of desflurane were identified as risk factors, in addition to
      risk factors of Apfel's score (female, non-smoker, history of motion sickness or
      PONV). Also, intraoperative remifentanil infusion was risk factor independent of
      postoperative opioid use. As the incidence of PONV was up to 50% according to the
      number of risk factors, risk-adapted, multimodal or combination therapy should be
      applied.

PMID- 25048509
TI  - Development and validation of the Korean version of the Female Sexual Function
      Index-6 (FSFI-6K).
AB  - PURPOSE: To evaluate the validity and reliability of the Korean version of the
      Female Sexual Function Index-6 (FSFI-6K). MATERIALS AND METHODS: Participants
      were recruited from February 2013 to July 2013. The primary survey was conducted
      for 220 participants, and a follow-up was conducted 3 weeks (+/-1 week) after the
      primary survey. The FSFI-6K data were analyzed and compared to the reference
      values in the original FSFI. RESULTS: Of the 220 participants, 199 (90.5%)
      returned to follow-up, 18 (8.2%) had no further contact, and 3 (1.4%) declined to
      respond. The internal consistency of the FSFI-6K as measured by Cronbach's alpha
      was 0.888 and the reliability based on test-retest intraclass correlation was
      0.606; these values were acceptable. The cutoff used for diagnosis of female
      sexual dysfunction by an receiver operating characteristics (ROC) curve was a
      score of 21; the sensitivity and specificity for this curve are 0.89 and 0.86,
      respectively. The area under the receiver operating curve was 0.948. CONCLUSION:
      The FSFI-6K has high internal consistency and acceptable reliability. This
      validated questionnaire can be used for the Korean population.

PMID- 25048510
TI  - Silicon dioxide particles deposited in vessels and cartilage of the femoral head.
AB  - Silicosis had been considered for decades as an illness with manifestations of
      lung fibrosis due to inhalation of overconcentrated SiO2 dust. To the best of our
      knowledge, studies have yet to report SiO2 deposits in any other tissues and
      organs. In the present case, while performing bilateral artificial total hip
      arthroplasty for one patient, we found that the articular cartilage of the
      bilateral femoral head was black. Therefore, specimens thereof were sent for
      pathological examination. Pathological examination (immunohistochemistry) and
      polarized light microscopy revealed the presence of considerable brown, acicular,
      rhombic, and crumb-like crystals. The crystals were mainly composed of SiO2. SiO2
      could deposit in vessels and femoral head cartilage via blood circulation. 

PMID- 25048511
TI  - Do intranodular macrocalcifications really play an important role in sonographic
      prediction of malignancy?

PMID- 25048512
TI  - A kernel-based multivariate feature selection method for microarray data
      classification.
AB  - High dimensionality and small sample sizes, and their inherent risk of
      overfitting, pose great challenges for constructing efficient classifiers in
      microarray data classification. Therefore a feature selection technique should be
      conducted prior to data classification to enhance prediction performance. In
      general, filter methods can be considered as principal or auxiliary selection
      mechanism because of their simplicity, scalability, and low computational
      complexity. However, a series of trivial examples show that filter methods result
      in less accurate performance because they ignore the dependencies of features.
      Although few publications have devoted their attention to reveal the relationship
      of features by multivariate-based methods, these methods describe relationships
      among features only by linear methods. While simple linear combination
      relationship restrict the improvement in performance. In this paper, we used
      kernel method to discover inherent nonlinear correlations among features as well
      as between feature and target. Moreover, the number of orthogonal components was
      determined by kernel Fishers linear discriminant analysis (FLDA) in a self
      adaptive manner rather than by manual parameter settings. In order to reveal the
      effectiveness of our method we performed several experiments and compared the
      results between our method and other competitive multivariate-based features
      selectors. In our comparison, we used two classifiers (support vector machine,
      [Formula: see text]-nearest neighbor) on two group datasets, namely two-class and
      multi-class datasets. Experimental results demonstrate that the performance of
      our method is better than others, especially on three hard-classify datasets,
      namely Wang's Breast Cancer, Gordon's Lung Adenocarcinoma and Pomeroy's
      Medulloblastoma. 

PMID- 25048513
TI  - Timing of urbanisation and cardiovascular risks in Thailand: evidence from 51 936
      members of the thai cohort study, 2005-2009.
AB  - BACKGROUND: Urban populations usually have higher levels of cardiovascular risk
      factors than rural populations in developing countries. However, association
      between cardiovascular risk factors and duration of urban dwelling, particularly
      for early stages of urban migrations, has not yet been adequately studied. We
      examined cardiovascular risks in relation to timing of urbanization in Thailand,
      paying attention to recent internal migrants. METHODS: Our study base was a large
      national cohort (n = 87 151) of distance-learning Thai open university students
      recruited in 2005 and followed up in 2009. After exclusion of longitudinal
      dropouts and reverse migrants, 51 936 remained for analyses. The information
      collected included historical residence, urban migration and its lifecycle
      timing, self-reported doctor-diagnosed diseases, and socio-demographic and
      personal attributes that could influence health. To relate cardiovascular
      outcomes (prevalence and incidence of hypertension and hyperlipidaemia) and life
      course urbanization status (ie at age 12, 4 years ago [2005] and at present
      [2009]), we applied logistic regression. Included in the models were 10 other
      covariates that could confound the urbanization effect. RESULTS: Recent migration
      (arriving within four years) among young cohort members (born after 1980) was
      associated with higher risk of hypertension (OR 1.80 for prevalence and 1.68 for
      four-year incidence). Higher hyperlipidaemia prevalence (and incidence) was
      associated with any urban dwelling. Recent migrants quickly developed
      hyperlipidaemia, particularly the youngest (born after 1980) and oldest
      participants (born before 1960). CONCLUSIONS: Increased cardiovascular risks
      appear among rural-urban migrants within four years after they arrive. Given the
      scale of continuing urbanization, interventions are needed to support and educate
      recent migrants in Thai cities.

PMID- 25048514
TI  - Investigation of oxyhemoglobin and carboxyhemoglobin ratios in right and left
      cardiac blood for diagnosis of fatal hypothermia and death by fire.
AB  - Few large-scale investigations have looked at the oxyhemoglobin ratio (%O2-Hb) or
      the carboxyhemoglobin ratio (%CO-Hb) in fatal hypothermia and death by fire as
      applicable to forensic medicine. We therefore retrospectively examined right and
      left cardiac blood samples for both %O2-Hb and %CO-Hb in 690 forensic autopsy
      cases. We therefore sought to establish reference values for the above forensic
      diagnoses, to compare %O2-Hb in fatal hypothermia with or without cardiopulmonary
      resuscitation (CPR), and to compare the relationship between %CO-Hb and smoking
      history. All %O2-Hb and %CO-Hb data were obtained during or immediately after
      autopsies using a portable CO-oximeter. Death by carbon monoxide (CO)
      intoxication and death by fire were excluded from the analysis involving smoking
      history. In fatal hypothermia, %O2-Hb in the left cardiac blood was significantly
      higher than that in the right cardiac blood, providing important evidence for
      fatal hypothermia. Furthermore, %O2-Hb in the left cardiac blood increases with
      CPR but that in the right cardiac blood increases in parallel. No correlation was
      observed between rectal temperature and %O2-Hb in the right and left cardiac
      blood, indicating that it is unlikely that postmortem cooling increases %O2-Hb in
      cardiac blood. %CO-Hb in smokers was significantly higher than that in non
      smokers, although the number of cigarettes smoked did not appear to be
      significant. When assessing death by fire, we identified that %CO-Hb of >10% was
      a reliable marker of antemortem CO inhalation, regardless of smoking history. 

PMID- 25048515
TI  - When to perform hepatic resection for intermediate-stage hepatocellular
      carcinoma.
AB  - Transcatheter arterial chemoembolization (TACE) is the first-line therapy
      recommended for patients with intermediate hepatocellular carcinoma (HCC).
      However, in clinical practice, these patients are often referred to surgical
      teams to be evaluated for hepatectomy. After making a treatment decision (e.g.,
      TACE or surgery), physicians may discover that the alternative treatment would
      have been preferable, which may bring a sense of regret. Under this premise, it
      is postulated that the optimal decision will be the one associated with the least
      amount of regret. Regret-based decision curve analysis (Regret-DCA) was performed
      on a Cox's regression model developed on 247 patients with cirrhosis resected for
      intermediate HCC. Physician preferences on surgery versus TACE were elicited in
      terms of regret; threshold probabilities (Pt) were calculated to identify the
      probability of survival for which physicians are uncertain of whether or not to
      perform a surgery. A survey among surgeons and hepatologists regarding three
      hypothetical clinical cases of intermediate HCC was performed to assess treatment
      preference domains. The 3- and 5-year overall survival rates after hepatectomy
      were 48.7% and 33.8%, respectively. Child-Pugh score, tumor number, and
      esophageal varices were independent predictors of survival (P<0.05). Regret-DCA
      showed that for physicians with Pt values of 3-year survival between 35% and 70%,
      the optimal strategy is to rely on the prediction model; for physicians with
      Pt<35%, surgery should be offered to all patients; and for Pt values>70%, the
      least regretful strategy is to perform TACE on all patients. The survey showed a
      significant separation among physicians' preferences, indicating that surgeons
      and hepatologists can uniformly act according to the regret threshold model.
      CONCLUSION: Regret theory provides a new perspective for treatment-related
      decisions applicable to the setting of intermediate HCC.

PMID- 25048516
TI  - Self-assembly of fullerene-based janus particles in solution: effects of
      molecular architecture and solvent.
AB  - Two molecular Janus particles based on amphiphilic [60]fullerene (C60 )
      derivatives were designed and synthesized by using the regioselective Bingel
      Hirsh reaction and the click reaction. These particles contain carboxylic acid
      functional groups, a hydrophilic fullerene (AC60 ), and a hydrophobic C60 in
      different ratios and have distinct molecular architectures: 1:1 (AC60 -C60 ) and
      1:2 (AC60 -2C60 ). These molecular Janus particles can self-assemble in solution
      to form aggregates with various types of micellar morphology. Whereas vesicular
      morphology was observed for both AC60 -C60 and AC60 -2C60 in tetrahydrofuran, in
      a mixture of N,N-dimethylformamide (DMF)/water, spherical micelles and
      cylindrical micelles were observed for AC60 -C60 and AC60 -2C60 , respectively. A
      mechanism of formation was tentatively proposed based on the effects of molecular
      architecture and solvent polarity on self-assembly. 

PMID- 25048517
TI  - Rare case of cerebello-pontine angle meningioma causing painful tic convulsif.

PMID- 25048518
TI  - A case of pediatric atypical prolactinoma: significance of a multidisciplinary
      treatment approach.

PMID- 25048520
TI  - Absorption, distribution, metabolism, and excretion considerations for the
      development of antibody-drug conjugates.
AB  - Antibody-drug conjugates (ADCs) are a class of therapeutics that are designed to
      deliver potent small-molecule drugs selectively to cells that express a specific
      target antigen while limiting systemic exposure to the drug. This is accomplished
      by conjugating a potent drug onto an antibody-based therapeutic with a linker
      that is exquisitely stable in plasma. The development of an effective ADC
      requires optimizing a number of design elements and an extensive understanding of
      absorption, distribution, metabolism/catabolism, and elimination (ADME) processes
      for the ADC construct. Furthermore, as ADCs are a combination of an antibody and
      small-molecule drug, understanding key aspects of the ADME of each individual
      component is needed. This review aims to provide considerations for the
      development of ADCs from an ADME point of view. 

PMID- 25048519
TI  - Unraveling the contribution of ectoenzymes to myeloma life and survival in the
      bone marrow niche.
AB  - The bone marrow provides a protected environment for generating a vast array of
      cell types. Bones are thus a dynamic source of structural components and soluble
      factors used either locally or at a distance from their site of production. We
      discuss the role of ectoenzymes in the bone niche where human myeloma grows.
      Selected ectoenzymes have been tested for their ability to promote production of
      substrates involved in signaling, synthesis of growth factors and hormones, and
      modulation of the immune response. Because of the difficulty of simultaneously
      tracking all these activities, we narrow our focus to events potentially
      influencing synthesis of adenosine (ADO), an important regulator of multiple
      biological functions, including local immunological tolerance. Our working
      hypothesis, to be discussed and partially tested herein, is that CD38, and likely
      BST1/CD157--both NAD(+) -consuming enzymes, are active in the myeloma niche and
      lead a discontinuous chain of ectoenzymes whose final products are exploited by
      the neoplastic plasma cell as part of its local survival strategy. Coadjuvant
      ectoenzymes include PC-1/CD203a, CD39, and CD73, which control the production of
      ADO. Results discussed here and from ongoing experiments indicate that the
      myeloma niche hosts the canonical, as well as alternative, pathways of ADO
      generation. Other possibilities are presented and discussed.

PMID- 25048521
TI  - Determination of the Al2O3 content in NaF-AlF3-CaF2-Al2O3 melts at 950  degrees C
      by Raman spectroscopy.
AB  - The in situ control of the chemical composition of industrial aluminum smelter is
      a challenge mainly for physicochemical reasons: high temperature, high
      surrounding electromagnetic field, and the highly corrosive molten salt
      electrolyte to deal with. In previous works, we proposed that Raman spectroscopy
      is a method of choice that could be adapted to real smelters. The laboratory
      study presented here relies on reproducible Raman spectra recorded on molten
      mixtures whose compositions are identical to those used during the production of
      aluminum. A normalization procedure for the Raman spectra is proposed based on
      the equilibria taking place in the bath. In addition, we discuss two quantitative
      models to determine the alumina content from the Raman spectra of the molten NaF
      AlF3-CaF2-Al2O3 electrolytes. Univariate and multivariate approaches are applied
      to determine both the COx (alumina content) and the CR (NaF/AlF3 molar ratio) by
      Raman spectroscopy without referring to an additional internal reference of
      intensity. The procedure was successfully tested and validated on industrial
      samples. 

PMID- 25048524
TI  - Computation of hemodynamics in tortuous left coronary artery: a morphological
      parametric study.
AB  - Coronary tortuosity (CT) would alter the local wall shear stress (WSS) and may
      become a risk factor for atherosclerosis. Here we performed a systematic
      computational study to relate CT morphological parameters to abnormal WSS, which
      is a predisposing factor to the formation of atherosclerotic lesions. Several
      idealized left coronary artery (LCA) models were created to conduct a series of
      morphological parametric studies, in which we concentrate on three specific
      morphological parameters, the center line radius (CLR), the bend angle (BA), and
      the length between two adjust bends (LBB). The time averaged WSS (TAWSS), the
      oscillatory shear index (OSI), and the time averaged WSS gradient (WSSGnd) were
      explored by using the computational fluid dynamics (CFD) method, in order to
      determine susceptible sites for the onset of early atherosclerosis. In addition,
      two realistic LCA models were reconstructed to further validate the finding's
      credibility. The CLR and LBB had great impact on the distributions of WSS-derived
      parameters, while the BA had minor impact on the hemodynamic of the tortuous
      arteries. Abnormal regions with low TAWSS (TAWSS < 0.5 Pa), high OSI (OSI > 0.1)
      and high WSSGnd (WSSGnd > 8) were observed at the inner wall of bend sections in
      the models with small CLR or small LBB. These findings were also confirmed in the
      realistic models. Severe CT with small CLR or LBB would lead to the formation of
      abnormal WSS regions at the bend sections and providing these regions with
      favorable conditions for the onset and/or progression of atherosclerosis. 

PMID- 25048522
TI  - Blood culture time to positivity in febrile infants with bacteremia.
AB  - IMPORTANCE: Blood cultures are often obtained as part of the evaluation of
      infants with fever and these infants are typically observed until their cultures
      are determined to have no growth. However, the time to positivity of blood
      culture results in this population is not known. OBJECTIVE: To determine the time
      to positivity of blood culture results in febrile infants admitted to a general
      inpatient unit. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, retrospective,
      cross-sectional evaluation of blood culture time to positivity. Data were
      collected by community and academic hospital systems associated with the
      Pediatric Research in Inpatient Settings Network. The study included febrile
      infants 90 days of age or younger with bacteremia and without surgical histories
      outside of an intensive care unit. EXPOSURES: Blood culture growing pathogenic
      bacteria. MAIN OUTCOMES AND MEASURES: Time to positivity and proportion of
      positive blood culture results that become positive more than 24 hours after
      placement in the analyzer. RESULTS: A total of 392 pathogenic blood cultures were
      included from 17 hospital systems across the United States. The mean (SD) time to
      positivity was 15.41 (8.30) hours. By 24 hours, 91% (95% CI, 88-93) had turned
      positive. By 36 and 48 hours, 96% (95% CI, 95-98) and 99% (95% CI, 97-100) had
      become positive, respectively. CONCLUSIONS AND RELEVANCE: Most pathogens in
      febrile, bacteremic infants 90 days of age or younger hospitalized on a general
      inpatient unit will be identified within 24 hours of collection. These data
      suggest that inpatient observation of febrile infants for more than 24 hours may
      be unnecessary in most infants.

PMID- 25048523
TI  - Affect and well-being similarity among older Indian spouses.
AB  - OBJECTIVES: Previous work suggests that husbands and wives are likely to share
      affective states so that depression or happiness in one spouse is predictive of
      depression or happiness in the other. Studies that have examined spousal affect
      similarity, however, have been concentrated in the Western world where the
      meaning of marriage may be different than it is in other cultural contexts.
      Marriage in India, unlike that in the United States, is focused on the extended
      family so that love and intimacy between spouses are downplayed. This study
      examined affect and well-being similarity between 603 older married couples in
      India using pilot data from the Longitudinal Aging Study of India. METHOD: We ran
      linear regression models to assess the relationship between the well-being states
      of husbands and wives using dyadic observations for four different measures:
      depressive symptoms, dissatisfaction with daily life, social isolation, and
      overall life satisfaction. RESULTS: Across all four measures, the well-being
      scores of one spouse were positively and significantly associated with the well
      being scores of the other. These associations did not vary by marital
      satisfaction, but were slightly stronger for respondents reporting poor health.
      CONCLUSION: Our increased understanding of social connectedness has prompted a
      shift from the consideration of single individuals to a broader understanding of
      individuals in the context of their social environments. The results of this
      study suggest that interventions designed to foster well-being among older adults
      in India might benefit from a focus on couples as a unit rather than individuals.

PMID- 25048525
TI  - Risk evaluation of selective renal arterial embolization in the treatment of
      delayed hemorrhage from renal artery pseudoaneurysm after partial nephrectomy.
AB  - Renal-artery pseudoaneurysm (RAP) is a well-described complication of partial
      nephrectomy. We aimed to evaluate the occurrence rate of delayed hemorrhage from
      RAP after partial nephrectomy, and to investigate the efficacy and safety of
      selective renal arterial embolization. Between January 2000 and December 2010,
      426 partial nephrectomies were performed at our institution for treatment of
      small renal mass (SRMs). A retrospective review of these cases revealed that 14
      patients developed a postoperative RAP (3.29 % incidence). We compared the
      clinical characteristics between the 14 patients with delayed renal hemorrhage
      and other 412 patients. RAP was diagnosed by renal angiography in 12 patients
      with delayed renal hemorrhage. Of the 12 patients, 10 patients were successfully
      treated with selective renal arterial embolization after presenting with symptoms
      postoperatively, 1 patient was treated with open surgery, and 1 patient was
      treated with nephrectomy. The other two patients showed no abnormalities in renal
      angiography, and the symptoms relieved by transfusion and hemostasis treatment.
      We found that tumor type, tumor size, tumor location, and surgical approach were
      significantly different between the 14 patients and other 412 patients. RAP
      showed a low incidence. The risk factors of RAP included renal cell carcinoma,
      tumor with large size, and tumor location. Most patients with delayed renal
      hemorrhage from RAP were successfully cured by selective renal arterial
      embolization. Therefore, selective renal arterial embolization can be used as the
      preferential therapy for RAP.

PMID- 25048526
TI  - Integration of cortical brain stimulation and exposure and response prevention
      for obsessive-compulsive disorder (OCD).

PMID- 25048527
TI  - Basic features of a cell electroporation model: illustrative behavior for two
      very different pulses.
AB  - Science increasingly involves complex modeling. Here we describe a model for cell
      electroporation in which membrane properties are dynamically modified by
      poration. Spatial scales range from cell membrane thickness (5 nm) to a typical
      mammalian cell radius (10 MUm), and can be used with idealized and experimental
      pulse waveforms. The model consists of traditional passive components and
      additional active components representing nonequilibrium processes. Model
      responses include measurable quantities: transmembrane voltage, membrane
      electrical conductance, and solute transport rates and amounts for the
      representative "long" and "short" pulses. The long pulse--1.5 kV/cm, 100 MUs-
      evolves two pore subpopulations with a valley at ~5 nm, which separates the
      subpopulations that have peaks at ~1.5 and ~12 nm radius. Such pulses are widely
      used in biological research, biotechnology, and medicine, including cancer
      therapy by drug delivery and nonthermal physical tumor ablation by causing
      necrosis. The short pulse--40 kV/cm, 10 ns--creates 80-fold more pores, all small
      (<3 nm; ~1 nm peak). These nanosecond pulses ablate tumors by apoptosis. We
      demonstrate the model's responses by illustrative electrical and poration
      behavior, and transport of calcein and propidium. We then identify extensions for
      expanding modeling capability. Structure-function results from MD can allow
      extrapolations that bring response specificity to cell membranes based on their
      lipid composition. After a pulse, changes in pore energy landscape can be
      included over seconds to minutes, by mechanisms such as cell swelling and pulse
      induced chemical reactions that slowly alter pore behavior.

PMID- 25048528
TI  - Blocking the bFGF/STAT3 interaction through specific signaling pathways induces
      apoptosis in glioblastoma cells.
AB  - We have reported that basic fibroblast growth factor (bFGF) demonstrates an
      intimate connection with signal transducer and activator of transcription 3
      (STAT3) in malignant brain tumor cells. However, its mechanisms are still
      unclear. In this study, we used inhibitors to block specific signaling pathways,
      including JAK, PI3K/Akt, and Src pathways, to explore how bFGF mediates crosstalk
      with STAT3 in two glioblastoma(GBM) cell lines: U251 (mutant p53) and U87 (wild
      type p53). Furthermore, we explored how the bFGF/STAT3 pathway affects GBM cell
      apoptosis. Our results suggest that bFGF can induce the activation of STAT3
      mainly through the JAK and PI3K/Akt pathways, and that siRNA-mediated knockdown
      of STAT3 markedly reduces the bFGF levels in U251 cells. Our results also suggest
      that STAT3 knockdown increases the expression of pro-apoptotic genes and
      decreases the expression of anti-apoptotic genes, subsequently collapsing the
      mitochondrial membrane potentials in vitro and impairs tumor growth in vivo. 

PMID- 25048529
TI  - Risk factors for leptomeningeal carcinomatosis in patients with brain metastases
      who have previously undergone stereotactic radiosurgery.
AB  - Our objective was to explore the hypothesis that the risk of leptomeningeal
      dissemination (LMD) in patients who underwent stereotactic radiosurgery (SRS) for
      brain metastases is influenced by the site of the primary cancer, the addition of
      whole brain radiation therapy (WBRT), surgical resection, and control over their
      systemic disease. We conducted a retrospective cohort analysis of 805 patients
      who were treated with SRS for brain metastases between 1999 and 2012 at the Wake
      Forest Baptist Medical Center, and excluded all patients with evidence of LMD
      before SRS. The primary outcome was LMD. Forty-nine of 795 patients developed LMD
      with a cumulative incidence of 6.2% (95% Confidence Interval (CI), 4.7-8.0).
      Median time from SRS to LMD was 7.4 months (Interquartile Range (IQR), 3.3-15.4).
      A colorectal primary site (Hazard Ratio (HR), 4.5; 95% CI 2.5-8.0; p < 0.0001),
      distant brain failure (HR, 2.0; 95% CI 1.2-3.2; p = 0.007), breast primary site
      (HR, 1.6; 95% CI 1.0-2.7; p = 0.05), the number of intracranial metastases at
      time of initial SRS (HR, 1.1; 95% CI 1.0-1.2; p = 0.02), and age (by 5-year
      interval) (HR, 0.9; 95% CI 0.8, 0.9; p = 0.0006) were independent factors
      associated with LMD. There was no evidence that surgical resection before SRS
      altered the risk of LMD (HR, 1.1; 95 % CI 0.6-2.0, p = 0.78). In patients who
      underwent SRS for brain metastases, a colorectal or breast primary site, distant
      brain failure, younger age, and an increased number of intracranial metastases
      were independently associated with LMD. Given its relative rarity as an outcome,
      multi-institutional prospective studies will likely be necessary to validate and
      quantify these relationships.

PMID- 25048530
TI  - Inverse spatial distribution of brain metastases and white matter
      hyperintensities in advanced lung and non-lung cancer patients.
AB  - The aim of this study was to test by means of a voxel-based approach the
      hypothesis that there is a different spatial distribution of brain metastases
      (BM) and white matter hyperintensities (WMH) and that the presence of WMH affects
      the location of BM in lung and non-lung cancer patients. Two-hundred consecutive
      cancer patients at first diagnosis of BM were included. Images were acquired
      using a 1.5 Tesla MRI system (Magnetom Avanto B13, Siemens, Erlangen, Germany).
      Axial FLAIR T2 weighted images and gadolinium-enhanced T1 weighted images were
      post-processed for segmentation, co-registration and analysis. Binary lesion
      masks were created for WMH and BM, using Volumes of Interest. Lesion probability
      maps were generated and the voxel-based lesion-symptom mapping approach was used
      to model each voxel and to calculate a non parametric statistics (Brunner-Munzel
      test) describing the differences between the groups. In the lung cancer group we
      found higher frequency of BM in WMH- than in WMH+ patients in the occipital lobe
      and the cerebellum. In contrast, BM were more frequent in the right frontal lobe
      in WMH+ than in WMH- patients. We suggest that there exists an inverse brain
      spatial distribution between WMH and BM. In lung cancer patients, the presence of
      WMH seems to shift the distribution of BM toward locations different than what it
      is expected based on primary tumor.

PMID- 25048531
TI  - Metastasis tumor-associated protein-2 knockdown suppresses the proliferation and
      invasion of human glioma cells in vitro and in vivo.
AB  - Metastasis tumor-associated protein 2 (MTA2) is a member of the MTA family that
      is closely associated with tumor progression and metastasis. However, the role of
      MTA2 in glioma cells remains unclear. The expression of MTA2 was measured using
      immunohistochemistry and western blotting in the human brain tumor tissue array
      and human glioma cell lines. The impact of MTA2 knockdown on GBM8401 and Hs683
      cell growth was evaluated by MTT assay and flow cytometry. Cell migration and
      invasion were analyzed by cell-migration assay and Matrigel invasion assay. In
      addition, we used subcutaneous tumor models to study the effect of MTA2 on the
      growth of glioma cells in vivo. We found that MTA2 protein and mRNA expression
      are higher in GBM8401 and Hs683 cells than in other glioma cells (M059 J, M059 K
      and U-87 MG), and glioma tumor tissue correlated significantly with tumor grade
      (P < 0.001). Knockdown of MTA2 expression significantly inhibited cell growth,
      cell migration and invasion, and induced G0/G1 phase arrest in human GBM8401 and
      Hs683 cells in vitro. Moreover, in vivo studies using subcutaneous xenografts in
      mice models indicate that MTA2 knockdown significantly inhibited tumorigenicity.
      These results indicate that MTA2 plays an important oncogenic role in the
      development and progression of gliomas.

PMID- 25048532
TI  - A magnetosome-associated cytochrome MamP is critical for magnetite crystal growth
      during the exponential growth phase.
AB  - Magnetotactic bacteria use a specific set of conserved proteins to biomineralize
      crystals of magnetite or greigite within their cells in organelles called
      magnetosomes. Using Magnetospirillum magneticum AMB-1, we examined one of the
      magnetotactic bacteria-specific conserved proteins named MamP that was recently
      reported as a new type of cytochrome c that has iron oxidase activity. We found
      that MamP is a membrane-bound cytochrome, and the MamP content increases during
      the exponential growth phase compared to two other magnetosome-associated
      proteins on the same operon, MamA and MamK. To assess the function of MamP, we
      overproduced MamP from plasmids in wild-type (WT) AMB-1 and found that during the
      exponential phase of growth, these cells contained more magnetite crystals that
      were the same size as crystals in WT cells. Conversely, when the heme c-binding
      motifs within the mamP on the plasmid was mutated, the cells produced the same
      number of crystals, but smaller crystals than in WT cells during exponential
      growth. These results strongly suggest that during the exponential phase of
      growth, MamP is crucial to the normal growth of magnetite crystals during
      biomineralization. 

PMID- 25048534
TI  - Medicare Part B Intensity and Volume Offset.
AB  - Under Medicare Part B, adjustments to the fee schedule are made under the
      assumption that physicians and hospitals make up for fee reductions through
      increased service provision called 'volume offsetting'. While historically,
      researchers have found evidence of volume offsetting, more recent studies have
      called into question its magnitude and existence. This study is the first to
      propose and empirically evaluate an alternative hypothesis of offsetting, namely
      the alteration of billed or provided services as a means of 'intensity
      offsetting'. Evaluating both forms of offsetting, it finds strong evidence of
      intensity offsetting and little to no evidence of volume offsetting. Simulating a
      10% reduction in the Medicare fee schedule, this study estimates that across
      different procedures between 22% and 59% of a fee reduction will be offset
      through alterations in service intensity.

PMID- 25048533
TI  - Motion patterns in activities of daily living: 3- year longitudinal follow-up
      after total shoulder arthroplasty using an optical 3D motion analysis system.
AB  - BACKGROUND: Total shoulder arthroplasty (TSA) can improve function in
      osteoarthritic shoulders, but the ability to perform activities of daily living
      (ADLs) can still remain impaired. Routinely, shoulder surgeons measure range of
      motion (ROM) using a goniometer. Objective data are limited, however, concerning
      functional three-dimensional changes in ROM in ADLs after TSA in patients with
      degenerative glenohumeral osteoarthritis. METHODS: This study included ten
      consecutive patients, who received TSA for primary glenohumeral osteoarthritis.
      The patients were examined the day before, 6 months, and 3 years after shoulder
      replacement as well. We compared them with a control group (n = 10) without any
      shoulder pathology and measured shoulder movement by 3D motion analysis using a
      novel 3 D model. The measurement included static maximum values, the ability to
      perform and the ROM of the ADLs "combing the hair", "washing the opposite
      armpit", "tying an apron", and "taking a book from a shelf". RESULTS: Six months
      after surgery, almost all TSA patients were able to perform the four ADLs (3 out
      of 40 tasks could not be performed by the 10 patients); 3 years postoperatively
      all patients were able to carry out all ADLs (40 out of 40 tasks possible). In
      performing the ADLs, comparison of the pre- with the 6-month and 3-year
      postoperative status of the TSA group showed that the subjects did not fully use
      the available maximum flexion/extension ROM in performing the four ADLs. The ROM
      used for flexion/extension did not change significantly (preoperatively 135
      degrees -0 degrees  -34 degrees  vs. 3 years postoperatively 131 degrees  -0
      degrees  -53 degrees ). For abduction/adduction, ROM improved significantly from
      33 degrees -0 degrees  -27 degrees  preoperatively to 76 degrees  -0 degrees  -35
      degrees  postoperatively. Compared to the controls (118 degrees ) the TSA group
      used less ROM for abduction to perform the four ADLs 3 years postoperatively.
      CONCLUSION: TSA improves the ability to perform ADL and the individual ROM in
      ADLs in patients with degenerative glenohumeral osteoarthritis over the course of
      3 years. However, TSA patients do not use their maximum available abduction ROM
      in performing ADLs. This is not related to limitations in active ROM, but rather
      may be caused by pathologic motion patterns, impaired proprioception or both.

PMID- 25048536
TI  - Abby E. Rudolph, winner of the American College of Epidemiology Annals of
      Epidemiology Award, 2013.

PMID- 25048538
TI  - Facile in situ synthesis of hierarchical porous Ni/Ni(OH)2 hybrid sponges with
      excellent electrochemical energy-storage performances for supercapacitors.
AB  - Herein, we report the in situ growth of single-crystalline Ni(OH)2 nanoflakes on
      a Ni support by using facile hydrothermal processes. The as-prepared Ni/Ni(OH)2
      sponges were well-characterized by using X-ray diffraction (XRD), SEM, TEM, and X
      ray photoelectron spectroscopy (XPS) techniques. The results revealed that the
      nickel-skeleton-supported Ni(OH)2 rope-like aggregates were composed of numerous
      intercrossed single-crystal Ni(OH)2 flake-like units. The Ni/Ni(OH)2 hybrid
      sponges served as electrodes and displayed ultrahigh specific capacitance
      (SC=3247 F g(-1)) and excellent rate-capability performance, likely owing to fast
      electron and ion transport, sufficient Faradic redox reaction, and robust
      structural integrity of the Ni/Ni(OH)2 hybrid electrode. These results support
      the promising application of Ni(OH)2 nanoflakes as advanced pseudocapacitor
      materials.

PMID- 25048539
TI  - Interstitial lung disease in undifferentiated forms of connective tissue disease.

PMID- 25048540
TI  - Treatment with Ziprasidone for schizophrenia patients with OCD.
AB  - Comorbidity of obsessive-compulsive disorder (OCD) has been observed in about 15%
      of schizophrenic patients and has been associated with poor prognosis. Therefore,
      there is a need for specific treatment options for these patients (schizo
      obsessive, ScOCD). This is an open, prospective study, aiming to test the
      efficacy of Ziprasidone (80-200mg/d) in ScOCD patients and comparing the response
      to the treatment between stable schizophrenic (N=16) and stable ScOCD (N=29)
      patients. Treatment effect with Ziprasidone was different in schizophrenic
      patients when stratified based on OCD comorbidity. Overall, the effect on OCD
      symptoms (as measured by the Yale Brown Obsessive Compulsive Scale, YBOCS) was
      found to be bimodal-either no response or exacerbation (for 45% of the patients,
      n=13) or significant improvement of symptoms (55%, n=16). Those who improved in
      OCD symptoms, improved also in negative and general schizophrenia symptoms, while
      ScOCD-unimproved group worsened in all symptoms. Whereas schizophrenic patients
      without OCD responded in a modest Gaussian distribution, they improved in
      schizophrenia negative symptoms and in general anxiety. This data suggests that
      schizo-obsessive disorder is a distinct and complex condition with more than one
      underlying pathogenesis. Definition of these ScOCD subgroups defined by their
      response to Ziprasidone might contribute to personalized medicine within the OCD
      schizophrenia spectrum. Moreover, this finding suggests that ScOCD may be
      considered as a special schizophrenic subtype and its inclusion in schizophrenia
      treatment studies need to be further explored due to its divergent response. 

PMID- 25048542
TI  - Avian influenza virus transmission to mammals.
AB  - Influenza A viruses cause yearly epidemics and occasional pandemics. In addition,
      zoonotic influenza A viruses sporadically infect humans and may cause severe
      respiratory disease and fatalities. Fortunately, most of these viruses do not
      have the ability to be efficiently spread among humans via aerosols or
      respiratory droplets (airborne transmission) and to subsequently cause a
      pandemic. However, adaptation of these zoonotic viruses to humans by mutation or
      reassortment with human influenza A viruses may result in airborne transmissible
      viruses with pandemic potential. Although our knowledge of factors that affect
      mammalian adaptation and transmissibility of influenza viruses is still limited,
      we are beginning to understand some of the biological traits that drive airborne
      transmission of influenza viruses among mammals. Increased understanding of the
      determinants and mechanisms of airborne transmission may aid in assessing the
      risks posed by avian influenza viruses to human health, and preparedness for such
      risks. This chapter summarizes recent discoveries on the genetic and phenotypic
      traits required for avian influenza viruses to become airborne transmissible
      between mammals. 

PMID- 25048541
TI  - Metabolic pathways for the whole community.
AB  - BACKGROUND: A convergence of high-throughput sequencing and computational power
      is transforming biology into information science. Despite these technological
      advances, converting bits and bytes of sequence information into meaningful
      insights remains a challenging enterprise. Biological systems operate on multiple
      hierarchical levels from genomes to biomes. Holistic understanding of biological
      systems requires agile software tools that permit comparative analyses across
      multiple information levels (DNA, RNA, protein, and metabolites) to identify
      emergent properties, diagnose system states, or predict responses to
      environmental change. RESULTS: Here we adopt the MetaPathways annotation and
      analysis pipeline and Pathway Tools to construct environmental pathway/genome
      databases (ePGDBs) that describe microbial community metabolism using MetaCyc, a
      highly curated database of metabolic pathways and components covering all domains
      of life. We evaluate Pathway Tools' performance on three datasets with different
      complexity and coding potential, including simulated metagenomes, a symbiotic
      system, and the Hawaii Ocean Time-series. We define accuracy and sensitivity
      relationships between read length, coverage and pathway recovery and evaluate the
      impact of taxonomic pruning on ePGDB construction and interpretation. Resulting
      ePGDBs provide interactive metabolic maps, predict emergent metabolic pathways
      associated with biosynthesis and energy production and differentiate between
      genomic potential and phenotypic expression across defined environmental
      gradients. CONCLUSIONS: This multi-tiered analysis provides the user community
      with specific operating guidelines, performance metrics and prediction hazards
      for more reliable ePGDB construction and interpretation. Moreover, it
      demonstrates the power of Pathway Tools in predicting metabolic interactions in
      natural and engineered ecosystems.

PMID- 25048543
TI  - Enhancement of influenza virus transmission by gene reassortment.
AB  - Influenza A virus is characterized by a genome composed of eight single-stranded,
      negative sense RNA segments, which allow for reassortment between different
      strains when they co-infect the same host cell. Reassortment is an important
      driving force for the evolution of influenza viruses. The ability of reassortment
      allows influenza virus to endlessly reinvent itself and pose a constant threat to
      the health of humans and other animals. Of the four human influenza pandemics
      since the beginning of the last century, three of them were caused by reassortant
      viruses bearing genes of avian, human or swine influenza virus origin. In the
      past decade, great efforts have been made to understand the transmissibility of
      influenza viruses. The use of reverse genetics technology has made it
      substantially easier to generate reassortant viruses and evaluate the
      contribution of individual virus gene on virus transmissibility in animal models
      such as ferrets and guinea pigs. H5, H7, and H9 avian influenza viruses represent
      the top three subtypes that are candidates to cause the next human influenza
      pandemic. Many studies have been conducted to determine whether the transmission
      of these avian influenza viruses could be enhanced by acquisition of gene
      segments from human influenza viruses. Moreover, the 2009 pdmH1N1 viruses and the
      triple reassortant swine influenza viruses were extensively studied to identify
      the gene segments that contribute to their transmissibility. These studies have
      greatly deepened our understanding of the transmissibility of reassortant
      influenza viruses, which, in turn, has improved our ability to be prepared for
      reassortant influenza virus with enhanced transmissibility and pandemic
      potential.

PMID- 25048544
TI  - ADP-ribosylation of P2X7: a matter of life and death for regulatory T cells and
      natural killer T cells.
AB  - ADP-ribosyltransferases comprise a family of enzymes originally discovered as
      bacterial toxins and later characterised also in mammals. In mice, the ADP
      ribosyltransferase ARTC2.2 is expressed at the surface of T lymphocytes and has
      been studied extensively. In the presence of extracellular NAD(+), ARTC2.2 ADP
      ribosylates several cell surface target proteins and thereby regulates their
      function. P2X7, an ATP-gated cation channel, has been discovered as a prominent
      ARTC2.2 target at the surface of mouse T cells. ADP-ribosylation of P2X7 in the
      presence of low micromolar extracellular NAD(+) induces long-lasting P2X7
      activation and triggers cell death. Regulatory T cell subsets (Tregs and NKT
      cells) are remarkably sensitive to NAD(+)-induced cell death (NICD). Thus,
      liberation of endogenous NAD(+) by stressed cells is now viewed as a danger
      signal promoting immune responses by hindering regulatory T cells. This review
      will highlight the recent discoveries on the in vivo role of the ARTC2.2/P2X7
      pathway triggered by the endogenous release of extracellular NAD(+), the relative
      sensitivity of lymphocytes subsets to this regulatory pathway and its
      pharmacological manipulation using camelid-derived ARTC2.2-blocking nanobodies. 

PMID- 25048550
TI  - Fibrosis: Regulation of fibrotic signalling by TGF-beta receptor tyrosine
      phosphorylation.

PMID- 25048549
TI  - Deferasirox nephrotoxicity-the knowns and unknowns.
AB  - In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical
      use as a first-line therapy for blood-transfusion-related iron overload.
      Nephrotoxicity is the most serious and frequent adverse effect of deferasirox
      treatment. This nephrotoxicity can present as an acute or chronic decrease in
      glomerular filtration rate (GFR). Features of proximal tubular dysfunction might
      also be present. In clinical trials and observational studies, GFR is decreased
      in 30-100% of patients treated with deferasirox, depending on dose, method of
      assessment and population studied. Nephrotoxicity is usually nonprogressive
      and/or reversible and rapid iron depletion is one of several risk factors. Scarce
      data are available on the molecular mechanisms of nephrotoxicity and the reasons
      for the specific proximal tubular sensitivity to the drug. Although deferasirox
      promotes apoptosis of cultured proximal tubular cells, the trigger has not been
      well characterized. Observational studies are required to track current trends in
      deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity
      in routine clinical practice, explore the effect on outcomes of various
      monitoring and dose-adjustment protocols and elucidate the long-term consequences
      of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be
      more common in the elderly; thus, specific efforts should be dedicated to
      investigate the effect of deferasirox use in this group of patients. 

PMID- 25048551
TI  - Does non-central nervous system tuberculosis increase the risk of ischemic
      stroke? A population-based propensity score-matched follow-up study.
AB  - BACKGROUND: Previous studies on the association between tuberculosis and the risk
      of developing ischemic stroke have generated inconsistent results. We therefore
      performed a population-based, propensity score-matched longitudinal follow-up
      study to investigate whether contracting non-central nervous system (CNS)
      tuberculosis leads to an increased risk of ischemic stroke. METHODS: We used a
      logistic regression model that includes age, sex, pre-existing comorbidities and
      socioeconomic status as covariates to compute the propensity score. A total of
      5804 persons with at least three ambulatory visits in 2001 with the principal
      diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The
      non-tuberculosis group consisted of 5804, propensity score-matched subjects
      without tuberculosis. The three-year ischemic stroke-free survival rates for
      these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox
      proportional hazards regression was used to estimate the effect of tuberculosis
      on the occurrence of ischemic stroke. RESULTS: During three-year follow-up, 176
      subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group
      (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in
      the tuberculosis group was 0.92 compared to the non-tuberculosis group (95%
      confidence interval: 0.73-1.14, P = 0.4299). CONCLUSIONS: Non-CNS tuberculosis
      does not increase the risk of subsequent ischemic stroke.

PMID- 25048552
TI  - "Passing children" and precarious pathways: on the contingency of reproductive
      life courses in Cameroon.
AB  - This article explores the implications of reproductive mishaps for the life
      courses of women in eastern Cameroon. Based on 15 months of anthropological
      fieldwork in a Gbigbil village, it describes local ideas about the expected
      unfolding of physical and social life trajectories, and the ways in which
      reproductive losses jeopardize these anticipated pathways. The life history of
      one informant shows that repeated child death can create a paradoxical situation
      in which a woman feels, at the same time, physically old and socially young, and
      that decisions for the future are informed by these contradictory sensations. The
      particular dynamics brought about by reproductive loss, then, challenge common
      views of the life course as a predefined pathway through consecutive and clearly
      defined life stages. Instead, they reveal that reproductive biographies are
      contingent and unpredictable, and that life stages may be paradoxically congruent
      rather than mutually exclusive. This, in turn, affects the way in which women
      give direction to their precarious reproductive pathways.

PMID- 25048554
TI  - DNA damages after SIM01 photodynamic treatment.
AB  - Photodynamic therapy (PDT) is a new approach to cancer treatment for a variety of
      malignant tumors. A new photosensitizer, 2,3-dihydro-5,15-di(3,5
      dihydroxyphenyl)porphyrin (SIM01), had been evaluated for its genotoxic effects
      on glioma cells (C6). Comet assay had been used to evaluate the potential
      genotoxic effect induced by SIM01 on the C6 cells. When SIM01 had been shown to
      be a powerful sensitizer no DNA strand break was detected in the absence of
      light. SIM01 localized in cytoplasm but not in the nucleus of the tumors cells,
      which supported the finding of undetectable DNA damage under darkness and low
      photodynamic dose. Cell exposure to 20Jcm(-2) after an incubation time of 2h with
      0, 0.25, 0.5, 2 or 4MUgmL(-1) induced less than 25% of cell death but significant
      Tail Moment changes. If DNA damage intensity increased according to SIM01 doses
      under light exposure, importance of repair seemed to increase proportionally to
      PDT-induced damage. Positive controls consisted of doxorubicin-treated C6 cells
      this mutagen being known to induce genetic damage. Whatever the conditions used
      SIM01 appeared to be less deleterious than doxorubicin. As the comet assay can
      not give us the certitude that no mutation, photoadducts or oxidative damage had
      been developed under light exposure this point will have to be verified with
      another mutagenicity assay. SIM01 appears to be safe from a mutagenic point of
      view something of importance as tumors of small volume in patients with a long
      lifespan are at first indicated for PDT. 

PMID- 25048555
TI  - Photodynamic therapy and endoscopic mucosal resection as minimally invasive
      approaches for the treatment of early esophageal tumors: Pre-clinical and
      clinical experience in Lausanne.
AB  - Esophageal cancer, when detected at an early stage, has a very good probability
      of being eradicated by surgery or radiotherapy. However, less aggressive
      treatments also tend to provide high rates of cure without the side effects of
      radical surgery or radiotherapy. Among them, photodynamic therapy and endoscopic
      mucosal resection have been experienced as alternative techniques for mucosal
      ablation in patients with superficial squamous-cell carcinoma (SCC) of the
      esophagus, or high-grade dysplasia and early stage adenocarcinoma arising in
      Barrett's esophagus. We report on the results of our clinical experience with
      photodynamic therapy and discuss about its advantages and limitations. We also
      present a pre-clinical study, which had evaluated the feasibility, efficacy, and
      safety of a promising new method of endoscopic mucosal resection (EMR) based on
      the use of a modified rigid esophagoscope. The animal model chosen was the sheep
      because of its similarities with humans regarding the thickness and histologic
      structure of the esophagus. This new resection modality offers a promising
      approach in comparison with other options currently available, namely EMRs
      performed with flexible gastroscopes. It appears to be superior in terms of the
      size of the resected specimen, the precision and regularity of the resection
      depth, and the accuracy of histological diagnosis with safety margins. 

PMID- 25048556
TI  - PDT for Barrett's esophagus: Status and unsolved problems.
AB  - PDT had been proposed in gastroenterology for various indications and the
      esophageal cancer treatment had been among the very first having been approved.
      However, PDT failed to be a real breakthrough. One reason for it was that
      although it had been approved for the palliative treatment of advanced tumors,
      PDT only has by nature a limited in-depth efficacy fitting better to the
      treatment and often the cure of "early cancers". For this reason PDT has also
      been proposed for the treatment of Barrett's esophagus (BE) with high-grade
      dysplasias. Barrett's mucosa (BM) is a field of a specialized metaplastic
      columnar epithelium replacing the normal stratified squamous epithelium or mucosa
      lining the distal esophagus. In this case, PDT has to destroy an area of thin
      tissues spread eventually over a wide area instead of a mass of tissues.
      Something important is that existing treatments allow the treatment of foci of
      dysplastic tissues but not the regression of the whole BM. BE is thus an unsolved
      medical problem having medical as well as economic consequences as BM being
      likely to transform into a cancer has to be carefully surveyed. The esophageal
      cancer, an adenocarcinoma, has to be surgically removed when it is possible
      something pretty heavy with a high morbidity. Economic burnt is also important
      with high survey costs independently to the additional surgical costs in case of
      diagnosed cancer. Treatments proposed for non or mild dysplastic BM regression
      have in common to have an inhomogenous impact on the target. Treatments for high
      grade dysplasia (HGD, the ultimate pathological step before cancer) are based on
      mucosectomy and are limited to small areas of tissues. Recently circumferential
      mucosectomy had been proposed but at a higher risk making it suitable only to
      highly experienced hands in infrequent indications. 

PMID- 25048553
TI  - Mechanisms in photodynamic therapy: part two-cellular signaling, cell metabolism
      and modes of cell death.
AB  - Photodynamic therapy (PDT) has been known for over a hundred years, but is only
      now becoming widely used. Originally developed as a tumor therapy, some of its
      most successful applications are for non-malignant disease. In the second of a
      series of three reviews, we will discuss the mechanisms that operate in PDT on a
      cellular level. In Part I [Castano AP, Demidova TN, Hamblin MR. Mechanism in
      photodynamic therapy: part one-photosensitizers, photochemistry and cellular
      localization. Photodiagn Photodyn Ther 2004;1:279-93] it was shown that one of
      the most important factors governing the outcome of PDT, is how the
      photosensitizer (PS) interacts with cells in the target tissue or tumor, and the
      key aspect of this interaction is the subcellular localization of the PS. PS can
      localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and
      plasma membranes. An explosion of investigation and explorations in the field of
      cell biology have elucidated many of the pathways that mammalian cells undergo
      when PS are delivered in tissue culture and subsequently illuminated. There is an
      acute stress response leading to changes in calcium and lipid metabolism and
      production of cytokines and stress proteins. Enzymes particularly, protein
      kinases, are activated and transcription factors are expressed. Many of the
      cellular responses are centered on mitochondria. These effects frequently lead to
      induction of apoptosis either by the mitochondrial pathway involving caspases and
      release of cytochrome c, or by pathways involving ceramide or death receptors.
      However, under certain circumstances cells subjected to PDT die by necrosis.
      Although there have been many reports of DNA damage caused by PDT, this is not
      thought to be an important cell-death pathway. This mechanistic research is
      expected to lead to optimization of PDT as a tumor treatment, and to rational
      selection of combination therapies that include PDT as a component. 

PMID- 25048557
TI  - PD/PDT for gynecological disease: A clinical review.
AB  - The evolution of diagnostic and interventional procedures for gynecologic disease
      has led to organ, sexual and reproductive sparing treatments. Photodiagnosis (PD)
      and photodynamic therapy (PDT) may play a great role for gynecological patients
      as both offer the potential to achieve these goals. PD/PDT for a wide variety of
      diagnostic and therapeutic interventions have shown potential for excellent
      clinical outcomes. However, significant limitations remains, both clinically and
      dosimetrically, that prevent consistent results. When those limitations are
      resolved PD/PDT could move to the forefront of gynecological therapy. This
      clinical review highlights the outcomes and shortcomings of PD/PDT through the
      peer reviewed literature for gynecological sites. 

PMID- 25048559
TI  - Photodynamic therapy in the palliative treatment of esophageal cancer.
AB  - Esophageal carcinoma is one of the most common cancers in the world and has an
      increasing incidence in Western civilisation and poor prognosis. In most cases
      palliative treatment is the only kind of therapy, which can be applied. In the
      Department of Digestive Tract Diseases, Medical University, Lodz, Poland, we have
      used PDT in two cases of palliative therapy of advanced esophageal cancer in
      cervical location of esophagus. We find PDT very promising, minimally invasive,
      safe and easy technique to perform for esophageal cancer of cervical
      localization. 

PMID- 25048558
TI  - Topical ALA-PDT modifies neutrophils' chemiluminescence, lymphocytes' interleukin
      1beta secretion and serum level of transforming growth factor beta1 in patients
      with nonmelanoma skin malignancies A clinical study.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been recognized as a noninvasive
      therapeutic approach for the effective treatment of tumors. It has been shown in
      studies conducted on malignant cell lines and various animal tumor models, that
      the interaction of photosensitizing substances with light leads to the release of
      cytotoxic substances and stimulates the immune response. PURPOSE: The aim of our
      study was to analyze the immune system response in patients undergoing
      photodynamic therapy due to basal cell carcinoma (BCC). METHODS: Patients with
      skin malignancies have been treated by 10% delta-aminolevulinic acid (ALA) (Medac
      GmbH, Wedel, Germany) topically and light from a diode laser. Blood samples were
      obtained from each patient twice in the same day: before and 4h after
      photodynamic treatment procedure. In patients' serum the concentration of
      transforming growth factor beta1 (TGF-beta1) was determined. Additionally the
      study has been conducted on lymphocytes and granulocytes from peripheral blood.
      In cell culture supernatants the concentration of interleukin 1beta (IL-1beta),
      interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor alpha
      (TNFalpha), the percentile composition of patients' lymphocytes and the
      chemiluminescence of neutrophils have been measured. RESULTS: We have observed a
      significant increase (p=0.015) in the intensity of the neutrophil
      chemiluminescence and significant diminution (p=0.006) of IL-1beta concentration
      in supernatants. Similarly the serum level of TGF-beta1 has been significantly
      decreased (p<0.001). CONCLUSION: It is very likely that human immune system
      activity is modified by topical ALA-PDT and may potentially contribute to its
      final outcome.

PMID- 25048560
TI  - PDT with TOOKAD((r)) studied in the chorioallantoic membrane of fertilized eggs.
AB  - BACKGROUND: The potential application of TOOKAD((r))-PDT for the treatment of
      blood vessels was investigated. TOOKAD((r)) (WST09), a novel palladium
      bacteriopheophorbide absorbs light in the near IR with a high quantum yield of
      intersystem crossing. Our study assessed the efficacy of this drug in inducing
      vascular damage with a view to its possible use in the treatment of age-related
      macular degeneration. METHODS: Vascular damage of TOOKAD((r))-PDT was studied in
      neovessels of the chorioallantoic membrane of fertilized eggs. Pharmacokinetic
      investigations were done by video microscopy and laser scanning microscopy. To
      induce damage vessels were irradiated with 763nm light from a diode laser.
      RESULTS: TOOKAD((r)) was accumulated in the vessels in the first minutes
      following injection. TOOKAD((r)) fluorescence was seen predominantly in the lumen
      and not in the vascular endothelial layer. Although fluorescence was very weak it
      could be attributed to TOOKAD((r)) from the fluorescence spectrum in the
      circulation. Damage assessment was done 24h after application of 763nm light. No
      significant difference in the degree of damage was observed with different short
      drug-light intervals (1-10min), but damage increased with the light energy dose.
      Closure of smaller vessels and vanished capillaries could be achieved by
      irradiation with 5J/cm(2) and a TOOKAD((r)) dose of 33MUg/embryo, corresponding
      to a phototoxic efficacy of 0.0062. CONCLUSIONS: From the results discussed in
      this work, TOOKAD((r)) could be a potential drug for the PDT of age-related
      macular degeneration in which the growth of new vessels in the choroids can lead
      to loss of vision.

PMID- 25048561
TI  - Relationship between vertical jump and maximal power output of legs and arms:
      effects of ethnicity and sport.
AB  - The hypothesis that ethnicity and sport practice influence the relationship
      between maximal power in cycling (P(max)) and countermovement jump (CMJ) has been
      studied by relating CMJ and P(max) in two groups (volleyball players, VB, and
      physical education students, PES) including subjects with Caucasian (67 C) or
      West African (39 WA) origins. Maximal power of the arms (P(max) Arms) was also
      measured. A two-way analysis of variance (groups * ethnicity) showed significant
      effects of both factors upon CMJ, which was higher in WA and VB, P = 0.002 and P
      < 0.001, respectively. Within WA, CMJ was significantly higher in VB (0.732 +/-
      0.057 m) than in PES (0.661 +/- 0.082 m), although there was no difference in
      P(max) (14.7 +/- 1.7 vs 14.7 +/- 1.9 W/kg). CMJ was significantly higher in WA
      (0.69 +/- 0.08 vs 0.65 +/- 0.09 m in C, P = 0.002) without significant
      interethnic difference in P(max) (14.7 +/- 1.8 in WA, and 14.8 +/- 1.9 W/kg in
      C). The CMJ-P(max) relationships were different in C and WA (P = 0.003).
      Therefore, CMJ predicted from P(max) would be underestimated in WA. The same
      difference was observed for the relationship between CMJ and P(max) Arms. These
      results were confirmed by the comparison with previous P(max) -CMJ relationship
      in the literature, collected in Caucasian and African subjects with the same
      protocols.

PMID- 25048562
TI  - Influence of green and gold kiwifruit on indices of large bowel function in
      healthy rats.
AB  - The effects of kiwifruit on large bowel health were investigated in healthy rats.
      Four-week old Sprague-Dawley rats were given diets containing 10% homogenized
      green kiwifruit, gold kiwifruit or 10% glucose solution (control) over 4 or 6 wk.
      Green kiwifruit increased the fecal output compared to control. Growth of certain
      bacterial species in cecum was influenced by both green and gold kiwifruit. A
      significant increase in cecal Lachnospiraceae in rats fed the green kiwifruit
      diet was observed at week 4. At week 6, green and gold kiwifruit diets assisted
      in improving colonic barrier function by upregulating the expression of mucin
      (MUC)-2, MUC3, Toll-like receptor (TLR)-4 or trefoil factor-3 genes. Gold
      kiwifruit consumption increased the colonic goblet cells per crypt at week 6.
      Significant negative correlations between E. coli and beta-defensin 1 and TLR4
      expression were observed. Consuming green and gold kiwifruit for 6 wk
      significantly altered the biomarkers of large bowel health; indicating that
      regularly consuming kiwifruit helps attain optimal digestive health. 

PMID- 25048563
TI  - Temperature effects on the tympanal membrane and auditory receptor neurons in the
      locust.
AB  - Poikilothermic animals are affected by variations in environmental temperature,
      as the basic properties of nerve cells and muscles are altered. Nevertheless,
      insect sensory systems, such as the auditory system, need to function effectively
      over a wide range of temperatures, as sudden changes of up to 10  degrees C or
      more are common. We investigated the performance of auditory receptor neurons and
      properties of the tympanal membrane of Locusta migratoria in response to
      temperature changes. Intracellular recordings of receptors at two temperatures
      (21 and 28  degrees C) revealed a moderate increase in spike rate with a mean Q10
      of 1.4. With rising temperature, the spike rate-intensity-functions exhibited
      small decreases in thresholds and expansions of the dynamic range, while spike
      durations decreased. Tympanal membrane displacement, investigated using
      microscanning laser vibrometry, exhibited a small temperature effect, with a Q10
      of 1.2. These findings suggest that locusts are affected by shifts in temperature
      at the periphery of the auditory pathway, but the effects on spike rate,
      sensitivity, and tympanal membrane displacement are small. Robust encoding of
      acoustic signals by only slightly temperature-dependent receptor neurons and
      almost temperature-independent tympanal membrane properties might enable locusts
      and grasshoppers to reliably identify sounds in spite of changes of their body
      temperature. 

PMID- 25048564
TI  - Simulating natural light and temperature cycles in the laboratory reveals
      differential effects on activity/rest rhythm of four Drosophilids.
AB  - Recent studies under semi-natural conditions have revealed various unique
      features of activity/rest rhythms in Drosophilids that differ from those under
      standard laboratory conditions. An additional afternoon peak (A-peak) has been
      reported for Drosophila melanogaster and another species D. malerkotliana while
      D. ananassae exhibited mostly unimodal diurnal activity. To tease apart the role
      of light and temperature in mediating these species-specific behaviours of four
      Drosophilid species D. melanogaster, D. malerkotliana, D. ananassae, and
      Zaprionus indianus we simulated gradual natural light and/or temperature cycles
      conditions in laboratory. The pattern observed under semi-natural conditions
      could be reproduced in the laboratory for all the species under a variety of
      simulated conditions. D. melanogaster and D. malerkotliana showed similar
      patterns where as D. ananassae consistently exhibited predominant morning
      activity under almost all regimes. Z. indianus showed clearly rhythmic activity
      mostly when temperature cycles were provided. We find that gradually changing
      light intensities reaching a sufficiently high peak value can elicit A-peak in D.
      melanogaster, D. malerkotliana, and D. ananassae even at mild ambient
      temperature. Furthermore, we show that high mid-day temperature could induce A
      peak in all species even under constant light conditions suggesting that this A
      peak is likely to be a stress response. 

PMID- 25048565
TI  - The Sydney Contained In Bag Morcellation technique.
AB  - STUDY OBJECTIVE: To demonstrate a modification of the Shibley single-port
      technique suitable for morcellation of large myomatous uteri after total
      laparoscopic hysterectomy in a contained environment within the abdominal cavity
      [1]. DESIGN: Step-by-step explanation of the technique using descriptive text and
      an educational video. SETTING: In light of recent concern about the use of power
      morcellators and increasing the risk of disseminating occult leiomyosarcomatous
      myoma fragments throughout the abdominal cavity, we propose this new technique
      for management of morcellation of large myomatous uteri after total laparoscopic
      hysterectomy, to contain the morcellation process and minimize the risk. This
      technique, which we have coined "Sydney Contained in Bag Morcellation" involves
      introduction of a sterile plastic bag (Dual Drawstring Bag, 460 * 460 mm;
      Southern Cross Hospital Supplies, Northmead, NSW, Australia) before introducing
      an optical port and the power morcellator. Before insertion this bag is modified
      in several ways to facilitate bag opening and specimen retrieval. The dual
      drawstring is removed and replaced with a 150-cm length of PDS I (polydioxanone)
      suture material as the new drawstring, with its exit at the mouth of the bag in
      the 6 o'clock position. Five stay sutures are placed around the bag mouth,
      corresponding to the 12, 1, 5, 7, and 11 o'clock positions. This assists with
      opening the mouth of the bag intraabdominally and enables orientation to be
      maintained. The bag is then inserted in a McCartney tube (Gates Healthcare,
      Cheshire, UK). Corresponding slits are made in the tip of the tube to enable the
      end of the stay sutures to be securely held in place during tube insertion. These
      ends are then retrieved using atraumatic graspers and exteriorized and clipped
      alongside their corresponding port sites. After hysterectomy the uterus is placed
      in the bag, and the stay sutures maintain the mouth opening. The bag is closed
      and its mouth exteriorized onto the abdominal wall at the site of the umbilical
      trocar. The 12-mm umbilical trocar is then replaced within the bag, and
      pseudopneumoperitoneum is created. Once established, an optical trocar is
      introduced via one of the lower quadrant port sites using a balloon tip trocar
      (Kii; Applied Medical, Rancho Santa Margarita, CA). The insufflation tubing is
      attached to this trocar, and the umbilical trocar is replaced with the
      morcellator device. Morcellation is performed under direct vision in a contained
      environment. Once complete, all fragments are removed, and the bag is washed out.
      The original pneumoperitoneum is re-established. The bag is then removed during
      aspiration to encourage negative pressure relative to the re-established
      pneumoperitoneum, minimizing aerosolized fragment leakage. INTERVENTION:
      Contained in bag morcellation of a large myomatous uterus during total
      laparoscopic hysterectomy. This technique has been specifically developed to
      address the concerns of morcellating large myomatous uteri after hysterectomy. In
      the case of supracervical hysterectomy or myomectomy, in which there would be no
      vaginal conduit to exploit, we use an endocatch bag, inserted in the usual
      manner, with reintroduction of the umbilical trocar within the mouth of the bag
      to enable creation of pseudopneumoperitoneum. Again, an optical trocar would be
      introduced in a lower lateral port, and morcellation would be performed under
      direct vision. An article describing this technique has recently been published
      [2]. CONCLUSION: The Sydney Contained in bag Morcellation technique offers a
      possible solution to the risk of dissemination of benign morcellated and
      potentially leiomyosarcomatous myoma fragments. Certain aspects of the procedure
      are key to its success. The stay sutures are essential to facilitate orientation
      and opening of the bag mouth. The McCartney tube enables easier insertion of the
      flaccid bag into the vagina, and the suture-retaining slits enable the mouth of
      the bag to be opened quickly and easily. We have used this technique in 5 cases
      with uteri ranging in weight from 350 to 978 g. Recently, similar techniques have
      been described for use in single-port surgery and conventional laparoscopy [1,2].
      Our technique is suitable for use with large uteri after total laparoscopic
      hysterectomy because the large capacity of the bag enables containment of uteri
      that would exceed the capacity of manually deployed specimen retrieval bags. This
      technique offers an alternative to vaginal morcellation, with the advantage of
      improved vision during morcellation and the ability to morcellate large uteri
      using a familiar instrument and view.

PMID- 25048566
TI  - Laparoscopic dissection and anatomy of sacral nerve roots and pelvic splanchnic
      nerves.
AB  - STUDY OBJECTIVE: To demonstrate the technique of laparoscopic dissection for
      identification of sacral nerve roots and pelvic splanchnic nerves. DESIGN: Case
      report (Canadian Task Force classification III). SETTING: Private practice
      hospital in Sao Paulo, Brazil. PATIENT: A 31-year-old woman with suspected
      iatrogenic and/or compression of sacral nerve roots. She reported debilitating
      pelvic, gluteal, and perineal unilateral left-sided pain (score 8 on a pain scale
      of 0-10), and had primary infertility with 1 previous failed attempt at in vitro
      fertilization. Surgical history included laparoscopic excision of endometriosis
      10 months before the procedure and left oophoroplasty during adolescence because
      of a benign neoplasm. INTERVENTIONS: Standard 4-puncture laparoscopy was
      performed. The peritoneum of the left pelvic sidewall was resected to preclude
      eventual residual endometriosis. This also enabled identification of uterine
      vessels including the deep uterine vein, which is the limit between the pars
      vascularis superiorly and the pars nervosa inferiorly in the uterine broad
      ligament. Surgery was using the laparoscopic neuro-navigation (LANN) technique,
      previously described by one of us (M. P.). For identification of the sacral
      roots, dissection was begun medial to the ureter and lateral to the uterosacral
      ligament. The Okabayashi pararectal space was entered as deep as possible via
      blunt dissection in avascular spaces. Hemostasis was performed using 5-mm bipolar
      forceps, and harmonic energy was not used. The hypogastric fascia was entered
      from medial to lateral, and the piriformis muscle was identified. The sacral
      nerve root S1 was identified lying over it. Dissection then proceeded caudally,
      and sacral roots S2 and S3 were sequentially identified. Small and delicate
      fibers forming the pelvic splanchnic nerves were isolated emerging from sacral
      roots S2 and S3. Other nerve fibers were identified caudally, probably
      representing pelvic splanchnic nerves emerging from S4. MEASUREMENTS AND MAIN
      RESULTS: The surgical operative time was 70 minutes, and bleeding was minimal. No
      suspected compression or iatrogenic injury was identified. The patient was
      discharged on the day after the procedure. At 8-month follow-up, she had partial
      resolution of pain (score 5, pain scale 0-10), and another failed attempt at in
      vitro fertilization was attributed to unsatisfactory quality of the embryos.
      There were no symptoms or dysfunctions attributable to manipulation of the
      nerves. CONCLUSION: Laparoscopy is a useful tool for identification of sacral
      roots and pelvic splanchnic nerves in suspected diseases. Its application in the
      field of neuropelveology can be expanded with proper knowledge and training.

PMID- 25048567
TI  - Long-term clinical outcomes following resectoscopic endometrial ablation of non
      atypical endometrial hyperplasia in women with abnormal uterine bleeding.
AB  - STUDY OBJECTIVE: To determine the feasibility, efficacy, and long-term clinical
      outcomes of resectoscopic endometrial ablation as primary treatment of simple
      endometrial hyperplasia (SH) and complex endometrial hyperplasia (CH) without
      atypia in women with abnormal uterine bleeding (AUB). DESIGN: Prospective follow
      up study (Canadian Task Force classification II-2). SETTING: Teaching hospital.
      PATIENTS: One hundred sixty-one women with hyperplasia, either SH (n = 107) or CH
      (n = 54). INTERVENTIONS: From January 1990 through December 2012, one of us
      performed 4729 primary resectoscopic endometrial ablation procedures in women
      with AUB. This group included 161 women with endometrial hyperplasia, identified
      either at office biopsy (n = 62) or incidentally during routine hysteroscopic
      endometrial ablation (n = 99). Endometrial tissue obtained at dilation and
      curettage and/or resected during resectoscopic surgery enabled identification of
      atypical hyperplasia in 6 patients (4 CH, 2 SH) and 1 patient with adenosarcoma.
      One patient with atypical CH and the patient with adenosarcoma underwent
      hysterectomy. The remaining 159 women, including 5 with atypical hyperplasia (3
      CH, 2 SH), underwent resectoscopic endometrial ablation (102 SH, 52 CH) as
      primary treatment. Patient median age was 50 years (range, 30-87 years), and body
      mass index was 32 (range, 17-59). Comorbidities included hypertension in 25
      patients, diabetes in 14, cerebrovascular disease in 3, cardiovascular disease in
      7, and hypothyroidism in 8. Office biopsy demonstrated proliferative endometrium
      in 68 patients, SH in 43, CH in 19, and inadequate findings in 13. In 18 women,
      we were unable to perform biopsy because of cervical stenosis, morbid obesity, or
      patient intolerance. Endometrium was resected in 120 patients, electrocoagulated
      in 34, and a combination of procedures in 5, using a 9-mm (26F) resectoscope,
      1.5% glycine, and 120W power. Patients were followed up annually. Three patients
      were lost to follow-up, and 1 died of an unrelated cause 5 years after surgery.
      MEASUREMENTS AND MAIN RESULTS: One uterine perforation occurred, which required
      no additional treatment. After endometrial ablation, SH was identified in 70
      patients, and CH in 35 patients. At a median follow-up of 7 years (range, 1.5
      18), 12 patients underwent hysterectomy to treat persistent bleeding (n = 6),
      benign ovarian cyst (n = 2), pelvic organ prolapse (n = 1), chronic pelvic pain
      (n = 2), or myomas (n = 1). Uterine histopathology in 11 patients demonstrated no
      residual endometrial hyperplasia. We were unable to obtain a pathology report for
      1 patient. The remaining 138 women were satisfied with the treatment, with no
      further bleeding or pain in 132 (95.7%). Six patients (4.3%) had monthly
      spotting. CONCLUSION: When performed by surgeons experienced in hysteroscopy,
      resectoscopic endometrial ablation is feasible, safe, and effective for treatment
      of SH and CH without atypia in women with AUB.

PMID- 25048568
TI  - Sydney contained in bag morcellation for laparoscopic myomectomy.
AB  - STUDY OBJECTIVE: To demonstrate a new technique of contained in bag morcellation
      of a myoma after laparoscopic myomectomy. DESIGN: Step-by-step explanation of the
      technique in a narrated video. INTERVENTION: Contained In Bag Morcellation of
      myoma after laparoscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: Recent
      controversy regarding the risk of disseminating occult leiomyosarcomatous tissue
      during morcellation means we need to revise our current approach to tissue
      extraction at laparoscopic myomectomy and morcellation in general. Herein we
      present a novel technique, conceived by Dr. Danny Chou, called the Sydney
      Contained In Bag Morcellation technique for laparoscopic myomectomy. In this
      technique an EndoCatch bag (EndoCatch II Auto Suture Specimen Retrieval Pouch;
      Covidien, Mansfield, MA) is introduced in the typical fashion, the myoma is
      retrieved, and the mouth of the bag is exteriorized onto the abdominal wall. A 12
      mm trocar is then introduced within the bag, and pneumoperitoneum is created
      before introducing an optical balloon tip port (KII Balloon Blunt Tip System;
      Applied Medical, Rancho Santa Margarita, CA) and the power morcellator device.
      Morcellation is then performed within the bag, under direct vision. This
      technique may offer a safer approach to morcellation because the bowel is not
      within the morcellation field and there is lower risk of disseminating occult
      leiomyosarcomatous tissue during morcellation. Subsequent to the morcellation
      process, suctioning of the bag removes any aerosolized particles of myoma,
      further minimizing the risk of possible dissemination. CONCLUSION: This technique
      may enable a minimally invasive approach to myomectomy to continue as a viable
      option in the era since the warning by the US Food and Drug Administration.

PMID- 25048569
TI  - Geriatric small bowel obstruction: an analysis of treatment and outcomes compared
      with a younger cohort.
AB  - BACKGROUND: Small bowel obstruction (SBO) is a common condition, but little is
      known about its presentation, management, and outcomes in geriatric patients.
      METHODS: A retrospective review was performed comparing geriatric (>=65 years of
      age) and nongeriatric patients admitted with SBO. Admission characteristics,
      treatment, and outcomes were compared. Data analysis included Student t test and
      chi-square test or Fisher's exact test. RESULTS: Among 80 geriatric and 136
      nongeriatric patients, no difference was observed among admission
      characteristics, treatment, time to or type of surgery, length of postoperative
      stay, or overall complications. Cardiac complications (15% vs 0%, P = .0082) and
      subacute care facility discharge (29% vs 5%, P < .001) were more common for
      geriatric patients. CONCLUSIONS: Compared with younger adults, elderly patients
      with SBO have similar presentations and overall outcomes with the exception of
      cardiac morbidity and discharge disposition. Preoperative attention to cardiac
      risk profile and discharge disposition discussion should be encouraged.

PMID- 25048570
TI  - The profile of successful applicants for endocrine surgery fellowships: results
      of a national survey.
AB  - BACKGROUND: The American Association of Endocrine Surgeons initiated a fellowship
      match in 2007. The profile of applicants who successfully match into an endocrine
      surgery (ES) fellowship has not previously been characterized. METHODS: An
      institutional review board-approved, web-based survey was distributed to recent
      and current ES fellows. RESULTS: The survey response rate was 62% (56/90). The
      overall mean age was 33 years (standard deviation +/-3), 54% were female, and 37%
      self-identified as non-white. Only 5% entered their surgical training with the
      aim of specializing in ES. During residency, respondents were exposed to high
      volumes of index ES cases. Sixty-two percent had dedicated research time. At the
      time of fellowship application, the median number of publications was 5 (range, 0
      to 25), and 30% of respondents had additional advanced degrees. CONCLUSION:
      Entering ES fellows has diverse backgrounds, with strong academic credentials.
      These data help inform the career mentoring of aspiring ES applicants.

PMID- 25048571
TI  - Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling.
AB  - BACKGROUND AND PURPOSE: Heteromerization of GPCRs is key to the integration of
      extracellular signals and the subsequent cell response via several mechanisms
      including heteromer-selective ligand binding, trafficking and/or downstream
      signalling. As the lysophosphatidylinositol GPCR 55 (GPR55) has been shown to
      affect the function of the cannabinoid receptor subtype 2 (CB2 receptor) in human
      neutrophils, we investigated the possible heteromerization of CB2 receptors with
      GPR55. EXPERIMENTAL APPROACH: The direct interaction of human GPR55 and CB2
      receptors heterologously expressed in HEK293 cells was assessed by co
      immunoprecipitation and bioluminescence resonance energy transfer assays. The
      effect of cross-talk on signalling was investigated at downstream levels by label
      free real-time methods (Epic dynamic mass redistribution and CellKey impedance
      assays), ERK1/2-MAPK activation and gene reporter assays. KEY RESULTS: GPR55 and
      CB2 receptors co-localized on the surface of HEK293 cells, co-precipitated in
      membrane extracts and formed heteromers in living HEK293 cells. Whereas
      heteromerization led to a reduction in GPR55-mediated activation of transcription
      factors (nuclear factor of activated T-cells, NF-kappaB and cAMP response
      element), ERK1/2-MAPK activation was potentiated in the presence of CB2
      receptors. CB2 receptor-mediated signalling was also affected by co-expression
      with GPR55. Label-free assays confirmed cross-talk between the two receptors.
      CONCLUSIONS AND IMPLICATIONS: Heteromers, unique signalling units, form in HEK293
      cells expressing GPR55 and CB2 receptors. The signalling by agonists of either
      receptor was governed (i) by the presence or absence of the partner receptors
      (with the consequent formation of heteromers) and (ii) by the activation state of
      the partner receptor.

PMID- 25048573
TI  - Microvessel density of mantle cell lymphoma. A retrospective study of its
      prognostic role and the correlation with the Ki-67 and the mantle cell lymphoma
      international prognostic index in 177 cases.
AB  - The clinical course and therapy of mantle cell lymphoma (MCL) are heterogeneous
      and often unsatisfactory. Prognostic factors are needed to stratify the patients.
      Microvessel density (MVD) has prognostic significance in some malignancies. There
      is little information about the vasculature of MCL, although some antiangiogenic
      drugs are in use. We studied MVD using systematic uniform random sampling and
      unbiased counting frames in immunohistochemical reactions with anti-CD34 antibody
      in pre-therapeutic extramedullary MCL samples of 177 patients. We analyzed the
      relationship of MVD to overall survival (OS) and progression-free survival (PFS),
      as well as to proliferative activity (Ki-67), mantle cell lymphoma prognostic
      index (MIPI), morphological variant, pattern of growth, and localization. MVD
      varied widely: range 54.6-503.6 vessels/mm(2), median 158.2 vessels/mm(2). Higher
      MVD was associated with bone marrow infiltration at the time of diagnosis (P =
      0.001). High MVD was associated with significantly worse OS (P = 0.04) only in
      patients treated with non-intensive (conventional) therapy. MVD correlated
      positively with MIPI scores but not with the proliferation, morphological
      variant, growth pattern, or localization. Univariate analysis identified a
      prognostic influence of morphological variant, MIPI, and proliferative activity
      on OS and PFS and a prognostic influence of bone marrow infiltration at the time
      of diagnosis on PFS. Multivariate analysis showed prognostic influence of MIPI
      and proliferative activity on OS and PFS only. In conclusion, this is the first
      clinicopathological study of MVD of MCL with long-term follow-up showing negative
      prognostic trends of high MVD in MCL and positive correlation of MVD and MIPI.

PMID- 25048572
TI  - Telomerase promoter mutations in cancer: an emerging molecular biomarker?
AB  - Cell immortalization has been considered for a long time as a classic hallmark of
      cancer cells. Besides telomerase reactivation, such immortalization could be due
      to telomere maintenance through the "alternative mechanism of telomere
      lengthening" (ALT) but the mechanisms underlying both forms of reactivation
      remained elusive. Mutations in the coding region of telomerase gene are very rare
      in the cancer setting, despite being associated with some degenerative diseases.
      Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and
      familial melanoma and subsequently in several cancer models, notably in gliomas,
      thyroid cancer and bladder cancer. The importance of these findings has been
      reinforced by the association of TERT mutations in some cancer types with tumour
      aggressiveness and patient survival. In the first part of this review, we
      summarize the data on the biology of telomeres and telomerase, available
      methodological approaches and non-neoplastic diseases associated with telomere
      dysfunction. In the second part, we review the information on telomerase
      expression and genetic alterations in the most relevant types of cancer (skin,
      thyroid, bladder and central nervous system) on record, and discuss the value of
      telomerase as a new biomarker with impact on the prognosis and survival of the
      patients and as a putative therapeutic target. 

PMID- 25048574
TI  - Patterns of psychotropic medicine use in pregnancy in the United States from 2006
      to 2011 among women with private insurance.
AB  - BACKGROUND: Psychiatric disorders are equally common during pregnancy as among
      non-pregnant women, and many of these conditions are treated with psychotropic
      medicines. Relatively little is known about patterns of use of many these agents
      during pregnancy, and specifically of how rates may have shifted during the last
      decade. We aimed to quantify the rate of pregnancy related exposures to
      categories of psychotropic medicines stratified according to the primary
      indication for use (antidepressants, antipsychotics, anxiolytics, and
      psychostimulants), trimester of pregnancy, trends over time and region, and
      indication for use. METHODS: We conducted a retrospective cohort study of
      pregnancies among women in the Truven Health MarketScan database (source
      population 70 million Americans), which captures person-specific clinical use and
      includes detailed information on filled prescriptions, hospitalizations and
      outpatient visits for all privately insured employees and their dependents. We
      classified psychotropic medicines of interest using ATC level 3 accordingly:
      antipsychotics (N05A); anxiolytics (N05B); antidepressants (N06A);
      psychostimulants, agents used for ADHD and cognitive enhancement (N06B). We also
      examined temporal and regional trends in use. RESULTS: We included 343,299 women
      who had a live birth between Jan 1, 2006 and Dec 31, 2011, of whom 10.3% were
      dispensed one or more psychotropic medicines during pregnancy. This rate varied
      from 6% to 15% between states. The rate of use of psychotropic medicines was
      relatively stable between 2006 and 2011. The most commonly used psychotropic
      medicines were selective serotonin reuptake inhibitors (5.1%) and benzodiazepine
      or benzodiazepine-like medicines (3.9%). Among psychotropic users, the most
      commonly associated psychiatric diagnosis was depression (25.0%), followed by
      anxiety disorders (24.4%). Approximately 1.6% of women used more than one
      category of psychotropic medicine in pregnancy, most commonly an antidepressant
      and an anxiolytic medicine (1.2%). CONCLUSIONS: Given this relatively high rate
      of use, the lack of evidence that the most frequently used medications improve
      birth outcomes and the safety concerns associated with both early and late
      pregnancy use for many frequently-used medications, there is a need for further
      study of factors driving psychotropic medication use during pregnancy.

PMID- 25048576
TI  - Suboptimal nutrition in moderately preterm infants.

PMID- 25048575
TI  - Differential regulatory role of pituitary adenylate cyclase-activating
      polypeptide in the serum-transfer arthritis model.
AB  - OBJECTIVE: Pituitary adenylate cyclase-activating polypeptide (PACAP) expressed
      in capsaicin-sensitive sensory neurons and immune cells has divergent functions
      in inflammatory and pain processes. This study was undertaken to investigate the
      involvement of PACAP in a mouse model of rheumatoid arthritis. METHODS: Arthritis
      was induced in PACAP(-/-) and wild-type (PACAP(+/+) ) mice by K/BxN serum
      transfer. General features of the disease were investigated by semiquantitative
      scoring, plethysmometry, and histopathologic analysis. Mechano- and
      thermonociceptive thresholds and motor functions were also evaluated. Metabolic
      activity was assessed by positron emission tomography. Bone morphology was
      measured by in vivo micro-computed tomography, myeloperoxidase activity and
      superoxide production by bioluminescence imaging with luminol and lucigenin,
      respectively, and vascular permeability by fluorescent indocyanine green dye
      study. RESULTS: PACAP(+/+) mice developed notable joint swelling, reduced
      grasping ability, and mechanical (but not thermal) hyperalgesia after K/BxN serum
      transfer. In PACAP(-/-) mice clinical scores and edema were significantly
      reduced, and mechanical hyperalgesia and motor impairment were absent, throughout
      the 2-week period of observation. Metabolic activity and superoxide production
      increased in the tibiotarsal joints of wild-type mice but were significantly
      lower in PACAP(-/-) animals. Myeloperoxidase activity in the ankle joints of
      PACAP(-/-) mice was significantly reduced in the early phase of arthritis, but
      increased in the late phase. Synovial hyperplasia was also significantly
      increased, and progressive bone spur formation was observed in PACAP-deficient
      mice only. CONCLUSION: In PACAP-deficient mice with serum-transfer arthritis,
      joint swelling, vascular leakage, hyperalgesia, and early inflammatory cell
      accumulation are reduced; in the later phase of the disease, immune cell function
      and bone neoformation are increased. Elucidation of the underlying pathways of
      PACAP activity may open promising new avenues for development of therapy in
      inflammatory arthritis.

PMID- 25048579
TI  - Chemical profile and antiacetylcholinesterase, antityrosinase, antioxidant and
      alpha-glucosidase inhibitory activity of Cynometra cauliflora L. leaves.
AB  - BACKGROUND: The aim of the current study was (i) to evaluate the bioactive
      potential of the leaf methanolic extract of Cynometra cauliflora L., along with
      its respective hexane, dichloromethane, ethyl acetate (EtOAc), n-butanol (n-BuOH)
      and aqueous fractions, in inhibiting the enzymes alpha-glucosidase,
      acetylcholinesterase (AChE) and tyrosinase as well as evaluating their
      antioxidant activities. (ii) In addition, in view of the limited published
      information regarding the metabolite profile of C. cauliflora, we further
      characterized the profiles of the EtOAc and n-BuOH fractions using liquid
      chromatography-diode array detection-electrospray ionization-tandem mass
      spectrometry. RESULTS: The leaf methanolic extract of C. cauliflora exhibited
      potent inhibition of all three enzymes and high antioxidant activity. The
      bioactivity was found to be concentrated in the EtOAc and n-BuOH fractions. A
      total of 18 compounds were identified in these bioactive fractions, comprising a
      procyanidin trimer, procyanidin tetramer, procyanidin hexamer, taxifolin
      pentoside, catechin, vitexin, isovitexin, kaempferol hexoside, quercetin
      pentoside, quercetin hexoside, apigenin-6-C-glucoside-8-C-glucoside, kaempferol
      coumaroyl hexoside and isorhamnetin hexoside. CONCLUSION: The results indicated
      that C. cauliflora, the leaves in particular, is a rich source of bioactive
      compounds and could be beneficial for further development of high-value
      phytomedicinal preparations and functional food products.

PMID- 25048577
TI  - Molecular characterisation and control of Acinetobacter baumannii isolates
      resistant to multi-drugs emerging in inter-intensive care units.
AB  - BACKGROUND: A nosocomial outbreak of Acinetobacter baumannii (AB) infections
      occurred among intensive care units (ICU) (surgery, medical, cardiovascular
      surgery, coronary unit) of Recep Tayyip Erdogan University Medical School (Rize,
      Turkey) between January 2011 and May 2012. The identification of isolates and
      clonal relation among them were investigated by molecular techniques. METHODS: A
      total of 109 AB isolates were obtained from 64 clinical materials from 54 ICU
      patients and 3 from the hands of healthcare workers (HCWs) of 42 environmental
      samples. The isolates were identified by 16S rDNA sequencing and OXA- specific
      PCR. The clonal relation between isolates was investigated by PFGE methods using
      ApaI restriction enzyme. RESULTS: All isolates were determined as AB by 16S rDNA
      sequencing and OXA-spesific PCR. While the blaOXA-51-like gene was amplified in
      all isolates, the blaOXA-23-like gene was amplified from 103 isolates. The PFGE
      pattern generated 9 pulsotypes and showed that the isolates from patients, HCWs,
      and the environment were genetically related. In 7 of these pulsotypes, there
      were 107 strains (98%) showing similar PFGE profiles that cannot be distinguished
      from each other, ranging from 2 to 53. The remaining 2 pulsotypes were comprised
      of strains closely associated with the main cluster. Two major groups were
      discovered with similarity coefficient of 85% and above. The first group
      consisted of 97 strains that are similar to each other at 92.7% rate, and the
      second group consisted of 12 strains that are 100% identical. CONCLUSIONS: The
      common utilization of the blood gas device among ICU was the reason for the
      contamination. AB strains can remain stable for a long period of time, although
      due to the disinfection procedures applied in hospitals, there is a small chance
      that the same clone might reappear and cause another epidemic. For that reason,
      the resistance profiles of the strains must be continuously followed with
      amplification-based methods, and these methods should be used to support the PFGE
      method in the short term.

PMID- 25048583
TI  - The CROWN initiative: journal editors invite researchers to develop core outcomes
      in women's health.
AB  - Clinical trials, systematic reviews and guidelines compare beneficial and non
      beneficial outcomes following interventions. Often, however, various studies on a
      particular topic do not address the same outcomes, making it difficult to draw
      clinically useful conclusions when a group of studies is looked at as a whole.
      This problem was recently thrown into sharp focus by a systematic review of
      interventions for preterm birth prevention, which found that among 103 randomised
      trials, no fewer than 72 different outcomes were reported. There is a growing
      recognition among clinical researchers that this variability undermines
      consistent synthesis of the evidence, and that what is needed is an agreed
      standardised collection of outcomes - a "core outcomes set" - for all trials in a
      specific clinical area. Recognising that the current inconsistency is a serious
      hindrance to progress in our specialty, the editors of over 50 journals related
      to women's health have come together to support The CROWN (CoRe Outcomes in
      WomeN's health) Initiative. 

PMID- 25048578
TI  - Amyloid burden, cerebrovascular disease, brain atrophy, and cognition in
      cognitively impaired patients.
AB  - BACKGROUND: We investigated the independent effects of Alzheimer's disease (AD)
      and cerebrovascular disease (CVD) pathologies on brain structural changes and
      cognition. METHODS: Amyloid burden (Pittsburgh compound B [PiB] retention ratio),
      CVD markers (volume of white matter hyperintensities [WMH] and number of
      lacunae), and structural changes (cortical thickness and hippocampal shape) were
      measured in 251 cognitively impaired patients. Path analyses were utilized to
      assess the effects of these markers on cognition. RESULTS: PiB retention ratio
      was associated with hippocampal atrophy, which was associated with memory
      impairment. WMH were associated with frontal thinning, which was associated with
      executive and memory dysfunctions. PiB retention ratio and lacunae were also
      associated with memory and executive dysfunction without the mediation of
      hippocampal or frontal atrophy. CONCLUSIONS: Our results suggest that the impacts
      of AD and CVD pathologies on cognition are mediated by specific brain regions.

PMID- 25048580
TI  - Real-time imaging of the epithelial-mesenchymal transition using microRNA-200a
      sequence-based molecular beacon-conjugated magnetic nanoparticles.
AB  - The epithelial-mesenchymal transition (EMT) plays important roles in tumor
      progression to metastasis. Thus, the development of an imaging probe that can
      monitor transient periods of the EMT process in live cells is required for a
      better understanding of metastatic process. Inspired by the fact that the mRNA
      expression levels of zinc finger E-box-binding homeobox 1 (ZEB1) increase when
      cells adopt mesenchyme characteristics and that microRNA-200a (miR-200a) can bind
      to ZEB1 mRNA, we conjugated molecular beacon (MB) mimicking mature miR-200a to
      magnetic nanoparticles (miR-200a-MB-MNPs) and devised an imaging method to
      observe transitional changes in the cells during EMT. Transforming growth factor
      beta1 treated epithelial cells and breast cancer cell lines representing both
      epithelial and mesenchymal phenotypes were used for the validation of miR-200a-MB
      MNPs as an EMT imaging probe. The real-time imaging of live cells acquired with
      the induction of EMT revealed an increase in fluorescence signals by miR-200a-MB
      MNPs, cell morphology alterations, and the loss of cell-cell adhesion. Our
      results suggest that miR-200a-MB-MNPs can be used as an imaging probe for the
      real-time monitoring of the EMT process in live cells. 

PMID- 25048584
TI  - [Diagnosis of upper urinary tract tumors. A pending challenge].
AB  - Early diagnosis of upper urinary tract tumors is not easy. The development of
      endoscopic equipment has expanded the group of patients candidates for minimally
      invasive treatment. Only by providing accurate tumor staging and grading can
      clinicians decide which patients should be offered conservative therapies. We
      need diagnostic methods that allow us to make an early and accurate diagnosis for
      these lesions, as well as safe follow-up. Our proposal is to present a review of
      the most used diagnostic method, their features, and future diagnostic tools. The
      diagnostic arsenal requires further improvement. Only through accurate diagnosis,
      we will be able to safely provide conservative treatment. Developing new
      diagnostic techniques seem to move us closer to this goal even more. We propose a
      working algorithm on the management of these lesions. 

PMID- 25048585
TI  - [Final results of an initiative aiming to improve the referrals from primary care
      to a Department of Urology].
AB  - OBJECTIVES: To test two interventions aiming at improving the compliance of
      primary health care physicians with an agreed-on protocol of referrals to a
      urology department. METHODS: Joint formative meetings (every six months) were
      celebrated throughout a 24-month period. Also a counseling telephone line was
      implemented. 18.088 referrals were analyzed. The effect of both expositions was
      tested comparing basal data (T0) with the performance at 6, 12, 18 and 24 months
      later (T1, T2, T3 and T4, respectively). An additional comparison was conducted
      to approach the results 1 year after the study ended (T5). RESULTS: 61.7% of the
      referrals at baseline complied with the protocol. A significant improvement was
      detected at T1 (compliance 73.4%, RR with respect to T0 1.19, 95% CI 1.14- 1.23).
      At T2, 73.7% of referrals were adequate (RR with respect to T0 1.19, 95% CI 1.15
      1.24). The percent of adequate referrals at T3 remained stable (73.4%, RR with
      respect to T0 1.18, 95% CI 1.15-1.23). Nevertheless, adequacy of referrals by the
      end of the second year (T4) significantly decreased (67.3%, RR with respect to
      T0, 1.09, 95% CI 1.05-1.12). Adequacy at T5 was almost identical to the basal
      (64.4%, RR with respect to T0, 1.04 95% CI 1.04-1.07). CONCLUSIONS: Learning
      activities can be effective in improving the quality of referrals from primary
      care to one urology department. Stopping the activities entails an immediate
      return to the basal standards.

PMID- 25048586
TI  - Predicting factors for recurrence in low-grade Ta primary bladder tumours.
AB  - OBJECTIVES: Ta bladder tumors constitute 53% of primary bladder neoplasms, 70% of
      them being low-grade (G1). These tumors present a 15- 38% chance of recurrence
      during the first year. The aim of this paper is to identify the predicting
      factors of the first recurrence in a series of TaG1 primary bladder tumors.
      METHODS: We have retrospectively analyzed patients who were diagnosed with TaG1
      primary bladder tumor by transurethral resection between 2004 and 2012. We
      established their tumor grade and pathological stage according to the WHO's
      classification guides for 1973 and 2004 as well as 2009's TNM. Those patients who
      were diagnosed before 2009 did not receive any adjuvant treatment. Those who were
      diagnosed later on received 40 mg of endovesical Mitomycin C during their
      immediate post operative period as their only treatment. We define recurrence as
      the presence of tumor after the first cystoscopy and relapse-free survival (RFS)
      as the period of time (in months) until the first recurrence appeared. Follow up
      constitutes the period of time (in months) until the last check-up or first
      recurrence. We also analyzed different variables: age, gender, smoking habits,
      muscular representation in the sample, size of the tumor (> or < 1 cm), multiple
      or single tumors and adjuvant treatment. The survival analysis was performed by
      the Kaplan-Meier method, using the long-rank test to evaluate the differences
      between groups. RESULTS: 68 patients were included in the study (73.5% men, 75%
      smokers). The average age was 61.9 years (the median being 58.5). Average follow
      up was 33.2 months (median 28.4). 35.3% of patients experienced recurrence.
      Average RFS was 19.2 +/- 12.7 months (median 13.5). The majority of tumors were
      of a single nature (77.9%), with a size of less than 1 cm (55.9%) and with muscle
      representation (52.9%). 57.4% of patients did not receive adjuvant treatment.
      Only the absence of adjuvant treatment was associated with recurrence in uni and
      multivariate analysis (p<0,001), with a relative risk of 17,5 IC95% (7,6-30,2).
      CONCLUSION: The absence of adjuvant therapy with Mitomycin C is the only factor
      that, in a statistically significant way, increases the risk of recurrence,
      regardless of demographic factors and the characteristics of the tumor.

PMID- 25048587
TI  - Results of the treatment of anterior pelvic organ prolapse using the Perigee(r)
      system.
AB  - OBJECTIVES: To study the efficacy and safety of the Perigee(r) System for the
      treatment of anterior vaginal prolapse in our experience with a medium term
      follow-up. METHODS: Prospective analysis on 48 consecutive patients with stage II
      IV cystocele diagnosed from June 2006 until June 2009 using the Pelvic Organ
      Prolapse Quantitation classification without other associated prolapses. All
      diagnoses were done by a single urological specialist and follow-up is between 3
      to 6 years. The questionnaire Patient Global Impression of Improvement was
      carried out before surgery, at the first follow up checking at one month, and at
      6 and 12 months. The variables evaluated were age, presence of obesity, parity,
      prior hysterectomy, ASA class and stage of prolapse. RESULTS: The result,
      evaluating the questionnaire Patient Global Impression of Improvement, was cured
      or improved in 40 (83.3%) patients and 87.5% according to the Pelvic Organ
      Prolapse Quantitation, with a recurrence rate of 6.25%. Intraoperative
      complications were observed in 12.5% of the patients, postoperative in 4.2% and
      41.5% after hospital discharge, pain being the most common complication (16.6%).
      The key variables for procedural failure were age 65 years >, obesity, parity >=
      2, prolapse stage >= III and prior hysterectomy (p <0.05). CONCLUSIONS: In our
      series the Perigee(r) System allows anatomic repair with less morbidity, hospital
      stay and recovery time.

PMID- 25048588
TI  - Is lower urinary tract dysfunction an early marker of Portuguese type familial
      amyloidotic polyneuropathy in women? Preliminary results.
AB  - Type 1 Portuguese Familial Amyloid Polyneuropathy was first observed in 1939 and
      described in 1951 by Corino Andrade. FAP is a rare autosomal dominant disease
      caused by a mutant gene in chromosome 18, characterized by a variant
      transthyretin in which valine is substituted for methionine at position 30 (ATTR
      V30M), affecting mainly young adults. ATTR V30M positivity does not imply
      disease, but the disease is only present with ATTR V30M in serum. The clinical
      manifestations of FAP on the pelvic floor and genitourinary system are frequent
      at early disease onset. Phenotypic diversity can depend on modulating agents in
      the deposition of the mutant TTR, such as incomplete penetration and
      environmental influence. Functional vesicourethral disorders appear to be
      primarily at the bladder filling phase, namely diminished bladder sensation, and
      associated with a decrease in detrusor contractility during the emptying phase.
      Unbalanced voiding takes place in this context, with high post-void residuals,
      increasing the rate of co-morbidity, namely recurrent urinary tract infections
      and chronic renal failure.This study describes the lower urinary tract
      dysfunctions in ATTR V30M positive carriers, particularly during the asymptomatic
      period and early stages of the disease, and additionaly it describes its
      association with the clinical evolution of the disease. In the preliminary phase
      of the study, the lower urinary tract dysfunction in FAP-women may present itself
      as an early manifestation in asymptomatic patients. Uroflowmetry and the
      evaluation of post-voiding residual volume are non-invasive and low cost tests
      that should be done during routine initial evaluation. Reduced bladder sensation
      and poor detrusor contractility may be considered initial markers of FAP. The
      neurogenic factor (bladder afferent neurons) appears to be mechanical in nature
      with myogenic repercussions. This further aggravates the bladder underactivity
      secondary to pelvic efferent parasympathetic neuropathy and amyloid infiltration
      in the bladder wall. Early diagnostic and therapeutic intervention may avoid
      secondary end stage renal disease. 

PMID- 25048589
TI  - Pudendal nerve block by transgluteal way guided by computed tomography in a woman
      with refractory pudendal neuralgia expressed like chronic perineal and pelvic
      pain.
AB  - OBJECTIVE: To demonstrate that the deep infiltration of the pudendal nerve guided
      by tomography is a good treatment option for patients with refractory neuralgia.
      METHOD: Two cases of pudendal neuralgia are presented, both expressed mainly with
      pain in the perineal and gluteal areas. Both cases had changes in the skin and
      one with urinary symptoms. A deep trans-gluteal infiltration guided by CT scan
      was performed, administering bupivacaine 0.25% with 80 mg methylprednisolone.
      RESULTS: In women, after infiltration, there was a decrease in pain from 6 to 3.
      In man infiltrations were performed monthly, completing 4. He reported pain
      reduction from 8 to 2. CONCLUSIONS: Pudendal Neuralgia diagnosis is unknown. The
      most common cause is inflammation of adjacent structures to the nerve frequently
      caused by falling. Diagnosis is mainly clinical. Trans-gluteal infiltration
      guided by CT scan is an effective option in treatment.

PMID- 25048590
TI  - Laparoscopic approach of primary bladder endometriosis.
AB  - OBJECTIVE: To report a case of primary bladder endometriosis treated with
      laparoscopic partial cystectomy. METHODS: We report the case of a 38 year old
      woman presenting with cyclic catamenial pain and hematuria who was diagnosed of
      bladder endometriosis by means of cystoscopy and MRI. Partial cystectomy using a
      laparoscopic approach was performed and symptoms disappeared. RESULTS: We report
      a well-documented case of primary bladder endometriosis and the laparoscopic
      approach used for its treatment. A review of the concept and the therapeutic
      alternatives are presented. CONCLUSIONS: Bladder endometriosis must be in mind
      when cyclic catamenial symptoms of pain and hematuria are present. When
      diagnosed, the laparoscopic approach must be considered the preferential option.

PMID- 25048591
TI  - Chylous ascytis causing abdominal distension after laparoscopic radical
      nephrectomy.
AB  - OBJECTIVE: To report a case of large chylous ascytis as a late complication of a
      laparoscopic nephrectomy for renal tumor. METHODS: A 62 year old patient was
      admitted with general deterioration and abdominal distension due to chylous
      ascites. Abdominal ultrasound and CT led to the diagnosis. Paracentesis confirmed
      the presence of a large peritoneal chylous fluid effusion. RESULTS: The patient
      was treated by punction and placement of a percutaneous drainage. A large amount
      of lymphatic fluid was obtained after punction with a progressive decrease.
      Medical treatment included low sodium and low fat diet, together with medium
      chain fast absorbing triglycerides, protein supplements, diuretics and
      somatostatin analogues (octeotride). The patient's progress was satisfactory
      after several days of treatment. CONCLUSIONS: Chylous ascites is a rare
      complication of laparoscopic nephrectomy, but it has a favorable course if
      managed conservatively. Meticulous clipping of the retroperitoneal lymph vessels
      is recommended to prevent the formation of chylous ascites, especially when
      discharging the renal vascular pedicle during nephrectomy or extensive
      lymphadenectomy.

PMID- 25048592
TI  - Bladder cavernous hemangioma. Case report.
AB  - OBJECTIVE: To report a case of a bladder cavernous hemangioma, as well as the
      main features of its diagnosis and treatment. METHODS: A 74 year old patient,
      regular smoker, presented with total macroscopic hematuria of moderate intensity
      with large rounded clots. On physical examination the patient's mucous membranes
      color was normal, and digital rectal examination showed a normal size prostate
      with fibroelastic consistency. RESULTS: An abdominal ultrasound was performed
      showing a slight bladder bottom thickening in addition to free clots and a
      homogeneous and normal prostate. Cystoscopy confirmed the presence of a sessile
      violet-colored rounded retrotrigonal tumor, 2 cm in diameter and 0.5 in height;
      it was immediately resected. The pathological study reported cavernous
      hemangioma. Patient's evolution has been satisfactory. CONCLUSIONS: Bladder
      cavernous hemangioma is a rare cause of hematuria, and transurethral resection of
      the small size lesions constitutes an effective option as a definitive surgical
      treatment.

PMID- 25048593
TI  - Urethral bleeding after open radical prostatectomy treated with selective
      arterial embolization. A rare complication.
AB  - OBJECTIVE: Gross hematuria in the immediate postoperative radical prostatectomy
      is a rare complication. According to different series reviewed, significant
      bleeding after this surgery appears between 0.5-1.5% of the cases. METHODS: 58
      year old male with localized prostate cancer who underwent open radical
      prostatectomy with preservation of the neurovascular bundles and a left accessory
      pudendal branch. In the 4th postoperative day patient presented severe hematuria
      and urethral bleeding requiring continuous bladder irrigation and blood
      transfusion. Given the persistence of bleeding despite conservative measures CT
      angiography was performed demonstrating active bleeding at a bulbar artery from
      the left internal pudendal artery without associated pelvic hematoma RESULTS:
      Given the findings selective embolization was performed with absorbable material
      stopping the bleeding. Three months later the patient maintains urinary
      continence and erectile function with tadalafil. CONCLUSIONS: Urethral bleeding
      after radical prostatectomy is a rare complication the cause of which is distal
      to the urinary sphincter unrelated to the pelvic vessels. The performance of CT
      angiography and subsequent embolization is the treatment of choice, avoiding open
      surgical revision, with less morbidity.

PMID- 25048594
TI  - Testicular fracture by closed trauma.

PMID- 25048595
TI  - Testicular rupture after gun shot injury.

PMID- 25048596
TI  - What can mice tell us about Foxp2 function?
AB  - Disruptions of the FOXP2 gene cause a rare speech and language disorder, a
      discovery that has opened up novel avenues for investigating the relevant neural
      pathways. FOXP2 shows remarkably high conservation of sequence and neural
      expression in diverse vertebrates, suggesting that studies in other species are
      useful in elucidating its functions. Here we describe how investigations of mice
      that carry disruptions of Foxp2 provide insights at multiple levels: molecules,
      cells, circuits and behaviour. Work thus far has implicated the gene in key
      processes including neurite outgrowth, synaptic plasticity, sensorimotor
      integration and motor-skill learning. 

PMID- 25048597
TI  - FoxP2 in songbirds.
AB  - Humans with mutations in the transcription factor FOXP2 display a severe speech
      disorder. Songbirds are a powerful model system to study FoxP2. Like humans,
      songbirds communicate via vocalizations that are imitatively learned during
      critical periods and this learning is influenced by social factors and relies on
      functionally lateralized neural circuits. During the past five years significant
      progress has been made moving from a descriptive to a more mechanistic
      understanding of how FoxP2 functions in songbirds. Current evidence from
      molecular and electrophysiological studies indicates that FoxP2 is important for
      shaping synaptic plasticity of specific neuron populations. One future goal will
      be to identify the transcriptional regulation orchestrated by FoxP2 and its
      associated molecular network that brings about these physiological effects. This
      will be key to further unravel how FoxP2 influences synaptic function and thereby
      contributes to auditory guided vocal motor behavior in the songbird model. 

PMID- 25048598
TI  - Patient Safety Policy in Long-Term Care: A Research Protocol to Assess Executive
      WalkRounds to Improve Management of Early Warning Signs for Patient Safety.
AB  - BACKGROUND: At many hospitals and long-term care organizations (such as nursing
      homes), executive board members have a responsibility to manage patient safety.
      Executive WalkRounds offer an opportunity for boards to build a trusting
      relationship with professionals and seem useful as a leadership tool to pick up
      on soft signals, which are indirect signals or early warnings that something is
      wrong. Because the majority of the research on WalkRounds has been performed in
      hospitals, it is unknown how board members of long-term care organizations
      develop their patient safety policy. Also, it is not clear if these board members
      use soft signals as a leadership tool and, if so, how this influences their
      patient safety policies. OBJECTIVE: The objective of this study is to explore the
      added value and the feasibility of WalkRounds for patient safety management in
      long-term care. This study also aims to identify how executive board members of
      long-term care organizations manage patient safety and to describe the
      characteristics of boards. METHODS: An explorative before-and-after study was
      conducted between April 2012 and February 2014 in 13 long-term care organizations
      in the Netherlands. After implementing the intervention in 6 organizations, data
      from 72 WalkRounds were gathered by observation and a reporting form. Before and
      after the intervention period, data collection included interviews,
      questionnaires, and studying reports of the executive boards. A mixed-method
      analysis is performed using descriptive statistics, t tests, and content
      analysis. RESULTS: Results are expected to be ready in mid 2014. CONCLUSIONS: It
      is a challenge to keep track of ongoing development and implementation of patient
      safety management tools in long-term care. By performing this study in
      cooperation with the participating long-term care organizations, insight into the
      potential added value and the feasibility of this method will increase.

PMID- 25048599
TI  - Elevated receptor for activated C kinase 1 expression is involved in
      intracellular Ca2+ influx and potentially associated with compromised regulatory
      T cell function in patients with asthma.
AB  - BACKGROUND: Regulatory T cells (T(regs)) are activated during anergy in response
      to T cell receptor (TCR) activation and functional immune suppression. Anergy of
      paediatric T(regs) is partially dependent on intracellular calcium mobility;
      following TCR activation, T(regs) do not exhibit increased intracellular Ca(2+)
      concentration ([Ca(2+) ](i)). OBJECTIVE: We determined whether [Ca(2+) ](i) in
      adult T(regs) defined their anergy, if intracellular Ca(2+) movement was linked
      to regulatory functions, whether [Ca(2+)](i) was indicative of asthma pathology,
      and the potential molecular mechanism responsible for Ca(2+) movement in T(regs).
      METHODS: T(regs) were purified by the magnetic bead method, and their regulatory
      functions were assessed by monitoring carboxyfluorescein succinimidyl ester
      labelled responder T cell proliferation. The Ca(2+) response of Fura-2-labelled
      cells was measured using a video image analysis system. To analyse the functions
      of T(regs) at the molecular level, we generated Jurkat Tet-On((r)) clones with
      doxycycline (Dox)-induced forkhead box P3 (FOXP3) protein expression. RESULTS:
      CD4(+) CD25(+) CD127(-/low) T(regs) from participants without asthma did not
      elicit Ca(2+) influx in response to TCR activation, exhibited little
      proliferation and suppressed proliferation of CD4(+) CD25(-) T cells. In
      contrast, under similar conditions, T(regs) from patients with asthma exhibited
      increased [Ca(2+)](i) and robust proliferation with partial loss of regulatory
      functions. FOXP3 protein levels in Tet-On((r)) clones were high after both 2- and
      5-day Dox treatment; however, 5-day cells were comparable with T(regs) from
      patients with asthma, whereas 2-day cells were similar to T(regs) from
      participants without asthma. Increasing [Ca(2+)](i) induced a high level of
      receptor for activated C kinase 1 (RACK1) expression in 5-day cells. CONCLUSIONS
      AND CLINICAL RELEVANCE: We confirmed that T(regs) in patients with asthma are
      functionally impaired and that the abnormal regulatory functions of these cells
      can be analysed by [Ca(2+)](i) following TCR engagement. Furthermore, the
      impaired functioning of T(regs) evident in patients with asthma may be due to a
      high level of RACK1.

PMID- 25048600
TI  - Selection on crop-derived traits and QTL in sunflower (Helianthus annuus) crop
      wild hybrids under water stress.
AB  - Locally relevant conditions, such as water stress in irrigated agricultural
      regions, should be considered when assessing the risk of crop allele
      introgression into wild populations following hybridization. Although research in
      cultivars has suggested that domestication traits may reduce fecundity under
      water stress as compared to wild-like phenotypes, this has not been investigated
      in crop-wild hybrids. In this study, we examine phenotypic selection acting on,
      as well as the genetic architecture of vegetative, reproductive, and
      physiological characteristics in an experimental population of sunflower crop
      wild hybrids grown under wild-like low water conditions. Crop-derived petiole
      length and head diameter were favored in low and control water environments. The
      direction of selection differed between environments for leaf size and leaf
      pressure potential. Interestingly, the additive effect of the crop-derived allele
      was in the direction favored by selection for approximately half the QTL detected
      in the low water environment. Selection favoring crop-derived traits and alleles
      in the low water environment suggests that a subset of these alleles would be
      likely to spread into wild populations under water stress. Furthermore,
      differences in selection between environments support the view that risk
      assessments should be conducted under multiple locally relevant conditions. 

PMID- 25048601
TI  - Total delay in treatment among smear positive pulmonary tuberculosis patients in
      five primary health centers, southern Ethiopia: a cross sectional study.
AB  - INTRODUCTION: The global burden of Tuberculosis (TB) remains enormous. Delay in
      TB diagnosis may lead to a higher infectious pool in the community and a more
      advanced disease state at presentation increasing the risk of mortality. This
      study is conducted to determine the total delay before treatment among smear
      positive Pulmonary Tuberculosis (PTB) patients. METHODS: A health institution
      based cross sectional study was conducted in five primary health centers in
      southern Ethiopia from June to December 2012. A total of 328 smear positive PTB
      patients were enrolled in the study. A structured and pre-tested questionnaire
      was used. Median patient, diagnostic, and treatment delays were calculated to
      determine the total delay. Multiple logistic regression analysis was used to
      identify factors associated with total delay. RESULTS: The median patient,
      diagnostic, treatment and total delays measured in days were 30 (IQR 20.2, 60), 7
      (IQR: 3, 14), 3 (IQR: 1, 4) and 45 (IQR: 34.5, 69.5) days respectively. Patients
      for whom treatment was not initiated within 45 days of onset of symptom(s) (total
      delay) constituted 49% of the study participants (59.5% among males and 39.2%
      among females; P<0.001). Total delay was found to be associated with: being
      female [AOR  = 0.34, 95% CI: 0.18-0.62], having attended tertiary level education
      [AOR  = 0.11, 95% CI: 0.02-0.55], perceived severity of stigma during the current
      TB disease course [AOR = 2. 18, 95% CI: 1.07, 4.42] and living in houses with
      higher family size [AOR = 0.26, 95% CI: 0.11, 0.61]. CONCLUSION: Total delay in
      treatment of TB is still high in the study area. Patient's sex, perceived stigma,
      educational status and family size are significantly contributing for total
      delay. Therefore, a concerted effort should be taken in order to improve health
      seeking behavior of the community on TB and to reduce delays from seeking care
      after experiencing TB symptoms.

PMID- 25048603
TI  - Colonoscopy reduced distal colorectal cancer risk and excess cancer risk
      associated with family history.
AB  - PURPOSE: Colonoscopy efficacy at preventing proximal colorectal cancer (CRC) is
      questioned, and little is known about efficacy in high-risk versus medium-risk
      populations. We investigated the relationship between colonoscopy screening,
      family history of colorectal cancer (FHCC), and CRC risk by site. METHODS: Among
      92,078 women of the E3N prospective cohort, 692 CRCs have been diagnosed after a
      median follow-up of 15.4 years. Cox proportional hazard models estimated adjusted
      hazards ratios according to subsites of cancer and FHCC. RESULTS: A personal
      history of colonoscopy (PHC; n = 37,470) was associated with decreased rectal and
      distal colon cancer risks (hazard ratio (HR) = 0.57; 95% Confidence Interval (CI)
      = 0.42-0.78 and HR = 0.37; 95% CI = 0.26-0.52, respectively), but not proximal
      colon cancer risk (HR = 0.87; 95% CI = 0.64-1.18). In women with no prior
      colonoscopy, those with FHCC had a 80% higher CRC risk than those without FHCC.
      In women with previous colonoscopy, CRC risk was similar in women with and
      without FHCC (p for interaction = 0.04). CONCLUSIONS: Results showed colonoscopy
      ability to prevent distal cancers, but not proximal cancers in women. Colonoscopy
      screening also reduced the excess risk of women with FHCC to that of women with
      no FHCC.

PMID- 25048602
TI  - Protein painting reveals solvent-excluded drug targets hidden within native
      protein-protein interfaces.
AB  - Identifying the contact regions between a protein and its binding partners is
      essential for creating therapies that block the interaction. Unfortunately, such
      contact regions are extremely difficult to characterize because they are hidden
      inside the binding interface. Here we introduce protein painting as a new tool
      that employs small molecules as molecular paints to tightly coat the surface of
      protein-protein complexes. The molecular paints, which block trypsin cleavage
      sites, are excluded from the binding interface. Following mass spectrometry, only
      peptides hidden in the interface emerge as positive hits, revealing the
      functional contact regions that are drug targets. We use protein painting to
      discover contact regions between the three-way interaction of IL1beta ligand, the
      receptor IL1RI and the accessory protein IL1RAcP. We then use this information to
      create peptides and monoclonal antibodies that block the interaction and abolish
      IL1beta cell signalling. The technology is broadly applicable to discover protein
      interaction drug targets. 

PMID- 25048604
TI  - Association between BRAFV600E and NRASQ61R mutations and clinicopathologic
      characteristics, risk factors and clinical outcome of primary invasive cutaneous
      melanoma.
AB  - PURPOSE: Previous studies suggest that solar UV exposure in early life is
      predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF
      mutation with sun exposure and disease prognosis has been less certain. We
      investigated the associations between BRAF(V600E) and NRAS(Q61R) mutations and
      known risk factors, clinicopathologic characteristics and clinical outcomes of
      melanoma in a case series of primary invasive cutaneous melanoma from the Nurses'
      Health Study (NHS). METHODS: Somatic BRAF(V600E) and NRAS(Q61R) mutations of 127
      primary invasive melanomas from the NHS cohort were determined by pyrosequencing
      using formalin-fixed, paraffin-embedded block tissues. Logistic regression
      analyses were performed to detect the associations of mutations with melanoma
      risk factors, and Kaplan-Meier method was used to examine associations between
      mutations and survival. RESULTS: The odds ratios for harboring BRAF(V600E)
      mutations were 5.54 (95% CI 1.19-25.8, p(trend) = 0.02) for women residing in
      states with UV index >= 7 versus those residing in states with UV index <=5 at 30
      years of age. Patients with BRAF(V600E) mutations tended to have shorter melanoma
      specific survival when compared to patients with wild type at both loci (median
      survival time 110 vs. 159 months) (p = 0.03). No association was found between
      NRASQ61R mutation and melanoma risk factors or melanoma-specific survival.
      CONCLUSIONS: BRAF(V600E) mutations in primary cutaneous melanomas were associated
      with residence in locations with medium and high UV indices in mid-life.
      BRAF(V600E) mutation may be associated with an unfavorable prognosis among
      melanoma patients.

PMID- 25048605
TI  - Laundry detergent pod ingestions: is there a need for endoscopy?
AB  - INTRODUCTION: Laundry detergent pod (LDP) exposures in children have resulted in
      several referrals to the emergency department. Signs and symptoms can include
      gastrointestinal symptoms (vomiting, drooling), neurological symptoms (depressed
      sensorium), or metabolic changes (lactic acidosis). There is limited literature
      on esophageal injury following LDP ingestions. CASE SERIES: We reviewed three
      cases of pediatric LDP ingestions that underwent an upper endoscopy in a tertiary
      care pediatric hospital. All of our patients were younger than 3 years old. The
      upper endoscopies revealed superficial esophageal erosions in two patients and
      erythema in the other. None of the patients had oral burns. Two of them developed
      swallowing dysfunction. Follow-up upper GI studies were normal. CASE DISCUSSION:
      Our three patients ingested laundry detergent pods and all of them developed some
      degree of esophageal injury despite the absence of oral erythema, ulcers, or
      swelling. A review of literature suggests LDP exposures are more severe than non
      pod detergents. Reasons as to why this may be remain unclear, although
      investigation into the ingredients and mode of delivery may help us to better
      understand. In a literature review, no esophageal strictures have been reported
      after LDP ingestion. We reviewed esophageal injury classification systems in an
      attempt to predict who may be at greatest risk for stricture based on initial
      findings. CONCLUSION: Our case series demonstrates it is hard to predict
      esophageal injury based on signs and symptoms. Based on a literature review, long
      term esophageal stricture is unlikely, but if gastrointestinal symptoms persist,
      it is reasonable to evaluate with an upper endoscopy. Larger studies are needed.

PMID- 25048606
TI  - Altered mental status and end organ damage associated with the use of
      gacyclidine: a case series.
AB  - INTRODUCTION: Over the past decade, there has been a sharp increase in the number
      of newly identified synthetic drugs. These new drugs are often derivatives of
      previously abused substances but have unpredictable toxicity. One of these drugs
      is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied
      as a neuroprotective agent in trauma and as a therapy of soman toxicity. There
      are no previous reports of its use as a drug of abuse. CASE REPORTS: During a two
      month period in the summer of 2013, a series of patients with severe agitation
      and end-organ injury were identified in an urban academic Emergency Department
      (ED). A urine drug of abuse screen was performed on all patients, and serum
      samples were sent for comprehensive toxicology analysis. A total of five patients
      were identified as having agitation, rhabdomyolysis, and elevated troponin (Table
      1). Three of the five patients reported use of methamphetamine, and all five
      patients had urine drug screens positive for amphetamine. Comprehensive serum
      analysis identified methamphetamine in three cases, cocaine metabolites in one
      case, and a potential untargeted match for gacyclidine in all five cases. No
      other drugs of abuse were identified. DISCUSSION: This is the first series of
      cases describing possible gacyclidine intoxication. The possible source of the
      gacyclidine is unknown but it may have been an adulterant in methamphetamine as
      all patients who were questioned reported methamphetamine use. These cases
      highlight the importance of screening for new drugs of abuse when patients
      present with atypical or severe symptoms. Gacyclidine has the potential to become
      a drug of abuse both by itself and in conjunction with other agents and toxicity
      from gacyclidine can be severe. It is the role of the medical toxicology field to
      identify new agents such as gacyclidine early and to attempt to educate the
      community on the dangers of these new drugs of abuse.

PMID- 25048608
TI  - Surgical techniques for uterine incision and uterine closure at the time of
      caesarean section.
AB  - BACKGROUND: Caesarean section is a common operation. Techniques vary depending on
      both the clinical situation and the preferences of the operator. OBJECTIVES: To
      compare the effects of 1) different types of uterine incision, 2) methods of
      performing the uterine incision, 3) suture materials and technique of uterine
      closure (including single versus double layer closure of the uterine incision) on
      maternal health, infant health, and healthcare resource use. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1
      September 2013) and reference lists of all identified papers. SELECTION CRITERIA:
      All published, unpublished, and ongoing randomised controlled trials comparing
      various types and closure of uterine incision during caesarean section. DATA
      COLLECTION AND ANALYSIS: Two review authors evaluated trials for inclusion and
      methodological quality without consideration of their results according to the
      stated eligibility criteria and extracted data independently. MAIN RESULTS: Our
      search strategy identified 60 studies for consideration, of which 27 randomised
      trials involving 17,808 women undergoing caesarean section were included in the
      review. Overall, the methodological quality of the trials was variable, with 12
      of the 27 included trials adequately describing the randomisation sequence, with
      less than half describing adequately methods of allocation concealment, and only
      six trials indicating blinding of outcome assessors.Two trials compared auto
      suture devices with traditional hysterotomy involving 300 women. No statistically
      significant difference in febrile morbidity between the stapler and conventional
      incision groups was apparent (risk ratio (RR) 0.92; 95% confidence interval (CI)
      0.38 to 2.20).Five studies were included in the review that compared blunt versus
      sharp dissection when performing the uterine incision involving 2141 women. There
      were no statistically significant differences identified for the primary outcome
      febrile morbidity following blunt or sharp extension of the uterine incision
      (four studies; 1941 women; RR 0.86; 95% CI 0.70 to 1.05). Mean blood loss (two
      studies; 1145 women; average mean difference (MD) -55.00 mL; 95% CI -79.48 to 
      30.52), and the need for blood transfusion (two studies; 1345 women; RR 0.24; 95%
      CI 0.09 to 0.62) were significantly lower following blunt extension.A single
      trial compared transverse with cephalad-caudad blunt extension of the uterine
      incision, involving 811 women, and while mean blood loss was reported to be lower
      following transverse extension (one study; 811 women; MD 42.00 mL; 95% CI 1.31 to
      82.69), the clinical significance of such a small volume difference is of
      uncertain clinical relevance. There were no other statistically significant
      differences identified for the limited outcomes reported.A single trial comparing
      chromic catgut with polygactin-910, involving 9544 women reported that catgut
      closure versus closure with polygactin was associated with a significant
      reduction in the need for blood transfusion (one study, 9544 women, RR 0.49, 95%
      CI 0.32 to 0.76) and a significant reduction in complications requiring re
      laparotomy (one study, 9544 women, RR 0.58, 95% CI 0.37 to 0.89).Nineteen studies
      were identified comparing single layer with double layer closure of the uterus,
      with data contributed to the meta-analyses from 14 studies. There were no
      statistically significant differences identified for the primary outcome, febrile
      morbidity (nine studies; 13,890 women; RR 0.98; 95% CI 0.85 to 1.12). Although
      the meta-analysis suggested single layer closure was associated with a reduction
      in mean blood loss, heterogeneity is high and this limits the clinical
      applicability of the result. There were no differences identified in risk of
      blood transfusion (four studies; 13,571 women; average RR 0.86; 95% CI 0.63 to
      1.17; Heterogeneity: Tau2 = 0.15; I2 = 49%), or other reported clinical outcomes.
      AUTHORS' CONCLUSIONS: Caesarean section is a common procedure performed on women
      worldwide. There is increasing evidence that for many techniques, short-term
      maternal outcomes are equivalent. Until long-term health effects are known,
      surgeons should continue to use the techniques they prefer and currently use.

PMID- 25048609
TI  - The use of Chinese herbal products and its influence on tamoxifen induced
      endometrial cancer risk among female breast cancer patients: a population-based
      study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The increased practice of traditional Chinese
      medicine (TCM) worldwide has raised concerns regarding herb-drug interactions.
      The purpose of our study was to analyze the use of Chinese herbal products (CHPs)
      and to estimate the influence of the use of CHP on tamoxifen induced endometrial
      cancer risk among female breast cancer patients in Taiwan. METHODS: All patients
      newly diagnosed with invasive breast cancer receiving tamoxifen treatment from
      January 1, 1998 to December 31, 2008 were selected from the National Health
      Insurance Research Database. The usage, frequency of service, and CHPs prescribed
      among the 20,466 tamoxifen-treated female breast cancer patients were analyzed.
      The logistic regression method was employed to estimate the odds ratios (ORs) for
      utilization of CHPs. Cox proportional hazard regression was performed to
      calculate the hazard ratios (HRs) for subsequent endometrial cancer for CHP non
      users and CHP users among female breast cancer patients who had undergone
      tamoxifen treatment. RESULTS: More than half of the subjects had ever used a CHP.
      Jia-Wei-Xiao-Yao-San (Augmented Rambling Powder) and Shu-Jing-Huo-Xue-Tang
      (Channel-Coursing Blood-Quickening Decoction) were the two most commonly used
      CHPs. The HR for the development of endometrial cancer among CHP users was 0.50
      fold (95% CI=0.38-0.64) compared to that of CHP non-users. CONCLUSION: More than
      half of the study subjects had ever used a CHP. Jia-Wei-Xiao-Yao-San was the most
      commonly used CHP. Among female breast cancer patients who had undergone
      tamoxifen therapy, CHP consumption decreased the risk of subsequent endometrial
      cancer. Exploring potential Chinese herb-tamoxifen interactions and integrating
      both healthcare approaches are beneficial to the overall health outcomes of
      tamoxifen-treated female breast cancer patients.

PMID- 25048610
TI  - In vivo and in vitro toxicological evaluation of the hydroalcoholic leaf extract
      of Ageratum conyzoides L. (Asteraceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In African traditional medicine, Ageratum
      conyzoides has been used as purgative, febrifuge, anti-ulcer and wound dressing.
      To date there is no safety information about long term use of Ageratum conyzoides
      which contains pyrrolizidine alkaloids, a class of hepatotoxic and carcinogenic
      phytochemicals. This study aims to evaluate the 90 days subchronic toxicity and
      in vitro toxicity of Ageratum conyzoides. MATERIALS AND METHODS: Three groups of
      8 rats (4 males and 4 females) received distilled water (control), 500 and 1000
      mg/kg of the extract daily for 90 consecutive days by oral gavage. The animals
      were observed daily for abnormal clinical signs and death. Body weight, relative
      organ weight, haematological and biochemical parameters of blood as well as
      heart, kidney, liver and spleen tissues histology were evaluated. RESULTS: After
      90 days administration, Ageratum conyzoides increased significantly (p<0.05) the
      relative weight of the liver, the spleen and kidney as compared to control group.
      Ageratum conyzoides increased also significantly (p<0.05) ALP, ALT, AST and blood
      glucose. Furthermore, an increase in the number of platelets associated with a
      normocytic and normochromic anaemia was observed. The cytotoxicity, determined by
      the MTT test and neutral red assay, has shown that the cytotoxicity of
      hydroalcoholic extract of Ageratum conyzoides and its total alkaloids was very
      close. CONCLUSIONS: Our results have shown that Ageratum conyzoides at 500 and
      1000 mg/kg can induce liver, kidney and haematological disorders. These toxics
      effects can be attributed to its total alkaloids especially to pyrrolizidine
      alkaloids which are present in this plant.

PMID- 25048611
TI  - Inflammatory stress increases hepatic CD36 translational efficiency via
      activation of the mTOR signalling pathway.
AB  - Inflammatory stress is an independent risk factor for the development of non
      alcoholic fatty liver disease (NAFLD). Although CD36 is known to facilitate long
      chain fatty acid uptake and contributes to NAFLD progression, the mechanisms that
      link inflammatory stress to hepatic CD36 expression and steatosis remain unclear.
      As the mammalian target of rapamycin (mTOR) signalling pathway is involved in
      CD36 translational activation, this study was undertaken to investigate whether
      inflammatory stress enhances hepatic CD36 expression via mTOR signalling pathway
      and the underlying mechanisms. To induce inflammatory stress, we used tumour
      necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) stimulation of the
      human hepatoblastoma HepG2 cells in vitro and casein injection in C57BL/6J mice
      in vivo. The data showed that inflammatory stress increased hepatic CD36 protein
      levels but had no effect on mRNA expression. A protein degradation assay revealed
      that CD36 protein stability was not different between HepG2 cells treated with or
      without TNF-alpha or IL-6. A polysomal analysis indicated that CD36 translational
      efficiency was significantly increased by inflammatory stress. Additionally,
      inflammatory stress enhanced the phosphorylation of mTOR and its downstream
      translational regulators including p70S6K, 4E-BP1 and eIF4E. Rapamycin, an mTOR
      specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and
      decreased the CD36 translational efficiency and protein level even under
      inflammatory stress resulting in the alleviation of inflammatory stress-induced
      hepatic lipid accumulation. This study demonstrates that the activation of the
      mTOR signalling pathway increases hepatic CD36 translational efficiency,
      resulting in increased CD36 protein expression under inflammatory stress. 

PMID- 25048612
TI  - Conceptions of learning research: variations amongst French and Swedish nurses. A
      phenomenographic study.
AB  - BACKGROUND: The development of nursing research capacity and interactions with
      cultural and structural issues is at various stages throughout Europe. This
      process appears to be remarkably similar irrespective of the country. Sweden has
      developed this capacity since the 1990s, whereas France is experiencing a
      transition. Nevertheless, knowledge about how nurses conceive their learning
      about nursing research and transitioning toward being researchers is scarce.
      OBJECTIVES: The aim of this study was to explore French and Swedish RNs'
      conceptions of research education and educational passage toward research and to
      describe how learning research contributes to the understanding of their norms
      and practices. DESIGN: A phenomenographic approach was used to understand and
      describe the qualitatively different ways in which French and Swedish RNs
      conceive research and its apprenticeship. SETTINGS AND PARTICIPANTS: A purposive
      maximum variation sampling of five French and five Swedish Nurse Researchers with
      PhDs. METHODS: Individual in-depth interviews conducted in France and Sweden
      between November 2012 and March 2013 were analysed using phenomenography.
      FINDINGS: The analysis revealed one main category, "Organisational factors to
      sustain individual apprenticeship". Three descriptive categories have emerged
      from the data and its variations amongst French and Swedish nurses: (1) entrance
      into research--modes of commitment; (2) nurses' engagement--the need for
      dedicated support; and (3) research as the means to resolve nursing situations.
      CONCLUSIONS: This study demonstrates how registered nurses have integrated
      nursing and researcher roles following different efficient paths. Education in
      nursing research is part of the strategy needed for the development of nursing
      research and is supported by the integration of research and practice.

PMID- 25048613
TI  - A novel method for measuring the ATP-related compounds in human erythrocytes.
AB  - The ATP-related compounds in whole blood or red blood cells have been used to
      evaluate the energy status of erythrocytes and the degradation level of the
      phosphorylated compounds under various conditions, such as chronic renal failure,
      drug monitoring, cancer, exposure to environmental toxics, and organ
      preservation. The complete interpretation of the energetic homeostasis of
      erythrocytes is only performed using the compounds involved in the degradation
      pathway for adenine nucleotides alongside the uric acid value. For the first
      time, we report a liquid chromatographic method using a diode array detector that
      measures all of these compounds in a small human whole blood sample (125 MUL)
      within an acceptable time of 20 min. The stability was evaluated for all of the
      compounds and ranged from 96.3 to 105.1% versus the day zero values. The
      measurement had an adequate sensitivity for the ATP-related compounds (detection
      limits from 0.001 to 0.097 MUmol/L and quantification limits from 0.004 to 0.294
      MUmol/L). This method is particularly useful for measuring inosine monophosphate,
      inosine, hypoxanthine, and uric acid. Moreover, this assay had acceptable
      linearity (r > 0.990), precision (coefficients of variation ranged from 0.1 to
      2.0%), specificity (similar retention times and spectra in all samples) and
      recoveries (ranged from 89.2 to 104.9%). The newly developed method is invaluable
      for assessing the energetic homeostasis of red blood cells under diverse
      conditions, such as in vitro experiments and clinical settings.

PMID- 25048614
TI  - Natural history of falls in a population-based cohort of patients with
      Parkinson's disease: an 8-year prospective study.
AB  - BACKGROUND: Prospective long-term studies of falls in Parkinson's disease (PD)
      are scarce. OBJECTIVE: To examine the development of falls over 8 years in a
      population-based cohort of ambulatory patients with PD, and to investigate
      predictors of future falls in non-fallers at baseline. METHODS: All patients were
      examined at baseline and after 4 and 8 years, including the UPDRS, MMSE,
      Montgomery and Aaberg Depression Rating Scale, Functional Comorbidity Index, and
      a clinical dementia interview. Logistic regression models were applied to
      investigate baseline risk factors for future falls. A total of 211 patients were
      included at baseline, whereas 121 and 64 were re-examined at 4 and 8 years,
      respectively. RESULTS: The prevalence of falls increased from 41% (87 of 211) at
      baseline to 72% (46 of 64) after 8 years of prospective follow-up (disease
      duration 16.2 +/- 4.8 years). Forty-seven non-falling patients at baseline
      completed all study visits, of these 68% (n = 32) changed fall status during
      follow-up. Predictive variables for current falling after 4 years were rare or
      occasional freezing of gait (OR 6.6, 95% CI 1.2-36.9), higher levodopa equivalent
      doses and more severe speech and axial impairment (both OR 1.3, 95% CI 1.0-1.7)
      in non-fallers at baseline. Higher baseline age was the only risk factor for
      current falling after 8 years. CONCLUSIONS: Nearly 3/4 of the PD cohort reported
      falling after 8 years of follow-up. Disease-specific gait and axial impairments
      were the major risk factors for future falls in non-fallers at baseline. This has
      implications for patient education and management.

PMID- 25048615
TI  - The impact of STN deep brain stimulation on speech in individuals with
      Parkinson's disease: the patient's perspective.
AB  - BACKGROUND: Speech disturbance is highly prevalent and disabling for individuals
      with Parkinson's disease (PD). Deep brain stimulation (DBS) has been found to
      adversely impact speech in a number of individuals with PD. This study
      investigated the differential speech profiles between individuals with PD with
      and without DBS from the patient's perspective. METHODS: A cross sectional
      research design was used. A total of 758 individuals with PD participated in this
      study, including 287 individuals with DBS and 471 individuals without DBS.
      Participants completed the Voice Handicap Index (VHI) and additional questions
      regarding speech symptoms and the impact of speech on social interaction.
      RESULTS: Independent of age and disease duration, there were statistically
      significant differences in perceived speech disturbance severity between the STN
      DBS group and Non-DBS group, with the DBS group reporting more severe symptoms as
      well as more significant symptom interference with social interaction and with
      daily experiences encountered relating to functional, physical, and emotional
      issues of a voice disorder (VHI). Low volume was the "most common" speech symptom
      for all individuals with PD patients across both age (younger and older) and
      disease duration (6-10 years and 11+ years) cohorts. DBS had the greatest adverse
      impact on "slurred speech." CONCLUSION: DBS therapy's contribution to speech
      disturbance is gaining more attention, and the speech symptoms ensuing from
      and/or being exacerbated by DBS are in the incipient stages of being
      investigated. Implications for DBS therapy on perceived quality of life are
      discussed.

PMID- 25048616
TI  - Quantum mechanics/molecular mechanics studies on the mechanism of action of
      cofactor pyridoxal 5'-phosphate in ornithine 4,5-aminomutase.
AB  - A computational study was performed on the experimentally elusive cyclisation
      step in the cofactor pyridoxal 5'-phosphate (PLP)-dependent D-ornithine 4,5
      aminomutase (OAM)-catalysed reaction. Calculations using both model systems and a
      combined quantum mechanics/molecular mechanics approach suggest that regulation
      of the cyclic radical intermediate is achieved through the synergy of the
      intrinsic catalytic power of cofactor PLP and the active site of the enzyme. The
      captodative effect of PLP is balanced by an enzyme active site that controls the
      deprotonation of both the pyridine nitrogen atom (N1) and the Schiff-base
      nitrogen atom (N2). Furthermore, electrostatic interactions between the terminal
      carboxylate and amino groups of the substrate and Arg297 and Glu81 impose
      substantial "strain" energy on the orientation of the cyclic intermediate to
      control its trajectory. In addition the "strain" energy, which appears to be
      sensitive to both the number of carbon atoms in the substrate/analogue and the
      position of the radical intermediates, may play a key role in controlling the
      transition of the enzyme from the closed to the open state. Our results provide
      new insights into several aspects of the radical mechanism in aminomutase
      catalysis and broaden our understanding of cofactor PLP-dependent reactions. 

PMID- 25048617
TI  - Precision synthesis: designing hot spots over hot spots via selective gold
      deposition on silver octahedra edges.
AB  - A major challenge in plasmonic hot spot fabrication is to efficiently increase
      the hot spot volumes on single metal nanoparticles to generate stronger signals
      in plasmon-enhanced applications. Here, the synthesis of designer nanoparticles,
      where plasmonic-active Au nanodots are selectively deposited onto the edge/tip
      hot spot regions of Ag nanoparticles, is demonstrated using a two-step seed
      mediated precision synthesis approach. Such a "hot spots over hot spots" strategy
      leads to an efficient enhancement of the plasmonic hot spot volumes on single Ag
      nanoparticles. Through cathodoluminescence hyperspectral imaging of these
      selective edge gold-deposited Ag octahedron (SEGSO), the increase in the areas
      and emission intensities of hot spots on Ag octahedra are directly visualized
      after Au deposition. Single-particle surface-enhanced Raman scattering (SERS)
      measurements demonstrate 10-fold and 3-fold larger SERS enhancement factors of
      the SEGSO as compared to pure Ag octahedra and non-selective gold-deposited Ag
      octahedra (NSEGSO), respectively. The experimental results corroborate well with
      theoretical simulations, where the local electromagnetic field enhancement of our
      SEGSO particles is 15-fold and 1.3-fold stronger than pure Ag octahedra and facet
      deposited particles, respectively. The growth mechanisms of such designer
      nanoparticles are also discussed together with a demonstration of the versatility
      of this synthetic protocol. 

PMID- 25048618
TI  - Posttranscriptional changes of serum albumin: clinical and prognostic
      significance in hospitalized patients with cirrhosis.
AB  - Beside the regulation of fluid distribution, human serum albumin (HSA) carries
      other activities, such as binding, transport, and detoxification of many
      molecules. In patients with cirrhosis, HSA exhibits posttranscriptional
      alterations that likely affect its functions. This study aimed at identifying the
      structural HSA alterations occurring in cirrhosis and determining their
      relationship with specific clinical complications and patient survival. One
      hundred sixty-eight patients with cirrhosis, 35 with stable conditions and 133
      hospitalized for acute clinical complications, and 94 healthy controls were
      enrolled. Posttranscriptional HSA molecular changes were identified and
      quantified by using a high-performance liquid chromatography/electrospray
      ionization mass spectrometry technique. Clinical and biochemical parameters were
      also recorded and hospitalized patients were followed for up to 1 year. Seven HSA
      isoforms carrying one or more posttranscriptional changes were identified.
      Altered HSA isoforms were significantly more represented in patients than in
      healthy controls. Conversely, the native, unchanged HSA isoform was significantly
      reduced in cirrhosis. Native HSA and most altered isoforms correlated with both
      Child-Pugh and Model for End-Stage Liver Disease scores. In hospitalized
      patients, oxidized and N-terminal truncated isoforms were independently
      associated with ascites, renal impairment, and bacterial infection. Finally, the
      native HSA and cysteinylated/N-terminal truncated isoforms were predictors of 1
      year survival, with greater prognostic accuracy than total serum albumin
      concentration. CONCLUSIONS: Extensive posttranscriptional changes of HSA,
      involving several molecular sites and increasing in parallel with disease
      severity, occur in patients with cirrhosis. Altered isoforms are independently
      associated with specific clinical complications, whereas the residual, native HSA
      isoform independently predicts patient survival. These findings support the
      concept of the "effective albumin concentration," which implies that the global
      HSA function is related not only to its serum concentration, but also to the
      preservation of its structural integrity.

PMID- 25048619
TI  - The political process in global health and nutrition governance: the G8's 2010
      Muskoka Initiative on Maternal, Child, and Newborn Health.
AB  - Why do informal, plurilateral summit institutions such as the Group of Eight (G8)
      major market democracies succeed in advancing costly public health priorities
      such as maternal, newborn, and child health (MNCH), even when the formal,
      multilateral United Nations (UN) system fails to meet such goals, when G8
      governments afflicted by recession, deficit, and debt seek to cut expenditures,
      and when the private sector is largely uninvolved, despite the growing popularity
      of public-private partnerships to meet global health and related nutrition, food,
      and agriculture needs? Guided by the concert-equality model of G8 governance,
      this case study of the G8's 2010 Muskoka Initiative on MNCH traces the process
      through which that initiative was planned within Canada, internationally prepared
      through negotiations with Canada's G8 partners, produced at Muskoka by the
      leaders in June, multiplied in its results by the UN summit in September, and
      reinforced by the new accountability mechanism put in place. It finds that the
      Muskoka summit succeeded in mobilizing major money and momentum for MNCH. This
      was due to the initiative and influence of children-focused nongovernmental
      organizations (NGOs), working with committed individuals and agencies within the
      host Canadian government, as well as supportive public opinion and the help of
      those in the UN responsible for realizing its Millennium Development Goals. Also
      relevant were the democratic like-mindedness of G8 leaders and their African
      partners, the deference of G8 members to the host's priority, and the need of the
      G8 to demonstrate its relevance through a division of labor between it and the
      new Group of Twenty summit. This study shows that G8 summits can succeed in
      advancing key global health issues without a global shock on the same subject to
      galvanize agreement and action. It suggests that, when committed, focused NGOs
      and government officials will lead and the private sector will follow, but that
      there will be a lag in the implementation needed to obtain the intended results.
      The need to improve the accompanying accountability mechanisms to improve
      implementation, thus, remains. 

PMID- 25048620
TI  - The protective effectiveness of an inactivated bovine ephemeral fever virus
      vaccine.
AB  - Bovine ephemeral fever (BEF) is an important viral disease of cattle. Despite the
      extensive use of inactivated vaccines for the prevention of BEF, a controlled
      study of their field effectiveness has never been performed. We conducted a large
      field effectiveness study of a BEF inactivated vaccine, during a large BEF
      outbreak. Neutralizing antibody titers measured in 385 heifers and calves 1 month
      after 2(nd) vaccination averaged 1:91.8 (CI95%=76.6-110). The effectiveness study
      enrolled 2780 cows in nine herds. In two herds cows vaccinated twice, 1 year
      before the outbreak and once 2-3 months before outbreak onset were compared with
      non-vaccinated cows. Average vaccine effectiveness of three vaccine doses
      compared to no vaccination was 47% (CI95%=34-57) in these herds. In two other
      herds cows vaccinated twice 1 year before the outbreak and twice again 2-3 months
      before outbreak were compared with cows vaccinated only twice 2-3 months prior to
      the outbreak. Average vaccine effectiveness of four doses compared to two doses
      was 49% (CI95%=25-65) in these herds. In five herds cows vaccinated twice 2-3
      months before outbreak onset were compared with non-vaccinated cows. This
      vaccination schedule was shown to be non-effective (average effectiveness=2%,
      CI95%=-14-17). Milk production analysis on one of the effected herds, in which
      56% vaccine effectiveness and an absolute reduction of 27% in morbidity were
      documented, revealed a net milk production loss of 175.9kg/sick cow (CI95%=127.9
      223.9) and an average gain of 37kg for each vaccinated cow (CI95%=-3.6-77.7).
      This study indicates that despite the fact that two vaccine doses of the tested
      inactivated vaccine elicited high titers of neutralizing antibodies, partial
      protection was induced only when at least 3 doses were administrated before
      natural challenge. 

PMID- 25048621
TI  - Electrochemical treatment of reverse osmosis concentrate on boron-doped
      electrodes in undivided and divided cell configurations.
AB  - An undivided electrolytic cell may offer lower electrochlorination through
      reduction of chlorine/hypochlorite at the cathode. This study investigated the
      performance of electrooxidation of reverse osmosis concentrate using boron-doped
      diamond electrodes in membrane-divided and undivided cells. In both cell
      configurations, similar extents of chemical oxygen demand and dissolved organic
      carbon removal were obtained. Continuous formation of chlorinated organic
      compounds was observed regardless of the membrane presence. However, halogenation
      of the organic matter did not result in a corresponding increase in toxicity
      (Vibrio fischeri bioassay performed on extracted samples), with toxicity
      decreasing slightly until 10AhL(-1), and generally remaining near the initial
      baseline-toxicity equivalent concentration (TEQ) of the raw concentrate (i.e.,
      ~2mgL(-1)). The exception was a high range toxicity measure in the undivided cell
      (i.e., TEQ=11mgL(-1) at 2.4AhL(-1)), which rapidly decreased to 4mgL(-1). The
      discrepancy between the halogenated organic matter and toxicity patterns may be a
      consequence of volatile and/or polar halogenated by-products formed in oxidation
      by OH electrogenerated at the anode. The undivided cell exhibited lower energy
      compared to the divided cell, 0.25kWhgCOD(-1) and 0.34kWhgCOD(-1), respectively,
      yet it did not demonstrate any improvement regarding by-products formation. 

PMID- 25048622
TI  - Green synthesis of gold nanoparticles for trace level detection of a hazardous
      pollutant (nitrobenzene) causing Methemoglobinaemia.
AB  - The present study involves a green synthesis of gold nanoparticles (Au-NPs) using
      Acacia nilotica twig bark extract at room temperature and trace level detection
      of one of the hazardous materials, viz. nitrobenzene (NB) that causes
      Methemoglobinaemia. The synthesis protocol demonstrates that the bioreduction of
      chloroauric acid leads to the formation of Au-NPs within 10min, suggesting a
      higher reaction rate than any other chemical methods involved. The obtained Au
      NPs have been characterized by UV-vis spectroscopy, X-ray diffraction,
      transmission electron microscopy, Energy-Dispersive X-ray Spectroscopy and
      Fourier Transform Infrared Spectroscopy. The electrochemical detection of NB has
      been investigated at the green synthesized Au-NPs modified glassy carbon
      electrode by using differential pulse voltammetry (DPV). The Au-NPs modified
      electrode exhibits excellent reduction ability toward NB compared to unmodified
      electrode. The developed NB sensor at Au-NPs modified electrode displays a wide
      linear response from 0.1 to 600MUM with high sensitivity of 1.01MUAMUM(-1)cm(-2)
      and low limit of detection of 0.016MUM. The modified electrode shows exceptional
      selectivity in the presence of ions, phenolic and biologically coactive
      compounds. In addition, the Au-NPs modified electrode exhibits an outstanding
      recovery results toward NB in various real water samples. 

PMID- 25048623
TI  - How antibody surface coverage on nanoparticles determines the activity and
      kinetics of antigen capturing for biosensing.
AB  - The antigen-capturing activity of antibody-coated nanoparticles is very important
      for affinity-based bioanalytical tools. In this paper, a comprehensive study is
      reported of the antigen-capturing activity of antibodies that are
      nondirectionally immobilized on a nanoparticle surface. Superparamagnetic
      nanoparticles (500 nm) were covalently functionalized with different quantities
      of monoclonal antibodies against cardiac troponin I (cTnI). At a low antibody
      surface coverage, up to 4% of the immobilized antibodies could capture antigen
      molecules from solution. At high antibody coverage (>=50 * 10(2) antibodies per
      nanoparticle, i.e., >= 64 * 10(2) antibodies per MUm(2)), the fraction of antigen
      capturing antibodies drops well below 4% and the number of active antibodies
      saturates at about 120 per nanoparticle. The fraction of active antibodies is
      small, yet surprisingly their dissociation constants (Kd) are low, between 10 and
      200 pM. In addition, the surface-binding activity of the antibody-coated
      nanoparticles was analyzed in an optomagnetic sandwich immunoassay biosensor,
      measuring cTnI in undiluted blood plasma. The data show that the immunoassay
      response scales with the number of active antibodies, increasing initially and
      saturating at higher antibody densities. The observations are summarized in a
      molecular sketch of the attachment, ordering, and functionality of antibodies on
      the nanoparticle surface. 

PMID- 25048624
TI  - Effect of gestational age and birth weight on the risk of strabismus among
      premature infants.
AB  - IMPORTANCE: Strabismus causes irreversible vision loss if not detected and
      treated early. It is unclear whether birth weight (BW) and gestational age (GA)
      are risk factors for strabismus. OBJECTIVE: To estimate the effect of BW and GA
      on the likelihood of premature infants developing strabismus. DESIGN, SETTING,
      AND PARTICIPANTS: In this longitudinal cohort analysis, we monitored a group of
      premature children from birth to determine the proportion that developed
      strabismus and the timing of the first strabismus diagnosis. Multivariable Cox
      regression analyses assessed the relationships of BW and GA with the development
      of strabismus. Regression models were adjusted for other risk factors for
      strabismus, sociodemographic factors, and ocular comorbidities. The analysis
      included 38,055 otherwise healthy children born prematurely who were enrolled for
      more than 6 months in a nationwide US managed care network between 2001 and 2011
      in communities throughout the United States. EXPOSURES: Birth weight less than
      2000 g or GA of 32 weeks or less. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs)
      for strabismus with 95% CIs. RESULTS: Of 38,055 otherwise healthy children who
      were born prematurely, 583 received a diagnosis of strabismus later in life. The
      cumulative incidence of strabismus was 3.0% at 5 years. Controlling for GA and
      other covariates, infants born with BW less than 2000 g had a 61% increased
      hazard (HR, 1.61; 95% CI, 1.22-2.13) of developing strabismus. Controlling for BW
      and other covariates, there was no significant association between strabismus and
      GA (HR, 0.98; 95% CI, 0.69-1.38). Among premature infants with BW of less than
      2000 g, a GA of 32 weeks or less conveyed no additional increased risk for
      developing strabismus relative to infants born after 32 weeks (HR, 1.27; 95% CI,
      0.86-1.88). In contrast, among infants with a GA of 32 weeks or less, BW of less
      than 2000 g conveyed a 14-fold increase in the risk of strabismus relative to BW
      of 2000 g or more (HR, 14.39; 95% CI, 1.99-104.14). CONCLUSIONS AND RELEVANCE:
      Independent of GA, very low BW conferred a large increase in strabismus risk
      among premature infants. In contrast, independent of BW, GA did not significantly
      affect the risk of strabismus. Updates to existing guidelines in the pediatric
      and ophthalmic literature should be considered, highlighting the importance of BW
      rather than GA and alerting clinicians about the need for careful monitoring of
      premature infants with low BW for strabismus.

PMID- 25048625
TI  - Complexity and demographic explanations of cumulative culture.
AB  - Formal models have linked prehistoric and historical instances of technological
      change (e.g., the Upper Paleolithic transition, cultural loss in Holocene
      Tasmania, scientific progress since the late nineteenth century) to demographic
      change. According to these models, cumulation of technological complexity is
      inhibited by decreasing--while favoured by increasing--population levels. Here we
      show that these findings are contingent on how complexity is defined: demography
      plays a much more limited role in sustaining cumulative culture in case formal
      models deploy Herbert Simon's definition of complexity rather than the particular
      definitions of complexity hitherto assumed. Given that currently available
      empirical evidence doesn't afford discriminating proper from improper definitions
      of complexity, our robustness analyses put into question the force of recent
      demographic explanations of particular episodes of cultural change.

PMID- 25048626
TI  - Psychosocial interventions in Alzheimer's disease and amnestic mild cognitive
      impairment: evidence for gender bias in clinical trials.
AB  - BACKGROUND: Alzheimer's disease (AD) affects twice as many women as men. Gender
      differences in symptom profile, living conditions, coping style and response
      might affect the outcome of psychosocial interventions (PSIs). OBJECTIVES: Our
      aim was to review gender differences in the available high-quality phase III
      trials on PSI in AD and amnestic mild cognitive impairment (aMCI) by considering
      the gender ratio in the investigated samples. DESIGN: Randomized controlled
      trials published in 2000-2012 were stepwise analyzed by statistically testing the
      representativeness of the gender ratio and examining reported gender differences.
      RESULTS: Forty-five studies (62% of 73 studies) reported gender ratios for each
      subsample and were included. In these studies, females were underrepresented in
      the control groups. In the 14 studies (19%) reporting analyses of gender
      differences, women were underrepresented in both intervention and control groups.
      However, in the six studies (8%) reporting significant gender differences in
      outcome, gender distribution was in accordance with prevalence rates. CONCLUSION:
      Current evidence is insufficient for reliable conclusions on gender differences
      in PSI outcome in AD and aMCI, as 81% of the available clinical trials either not
      reported the gender ratio of their samples, or underrepresent females. Further
      research is needed addressing gender differences, and clinical trials should
      routinely control for gender bias.

PMID- 25048627
TI  - Clinical prediction from structural brain MRI scans: a large-scale empirical
      study.
AB  - Multivariate pattern analysis (MVPA) methods have become an important tool in
      neuroimaging, revealing complex associations and yielding powerful prediction
      models. Despite methodological developments and novel application domains, there
      has been little effort to compile benchmark results that researchers can
      reference and compare against. This study takes a significant step in this
      direction. We employed three classes of state-of-the-art MVPA algorithms and
      common types of structural measurements from brain Magnetic Resonance Imaging
      (MRI) scans to predict an array of clinically relevant variables (diagnosis of
      Alzheimer's, schizophrenia, autism, and attention deficit and hyperactivity
      disorder; age, cerebrospinal fluid derived amyloid-beta levels and mini-mental
      state exam score). We analyzed data from over 2,800 subjects, compiled from six
      publicly available datasets. The employed data and computational tools are freely
      distributed ( https://www.nmr.mgh.harvard.edu/lab/mripredict), making this the
      largest, most comprehensive, reproducible benchmark image-based prediction
      experiment to date in structural neuroimaging. Finally, we make several
      observations regarding the factors that influence prediction performance and
      point to future research directions. Unsurprisingly, our results suggest that the
      biological footprint (effect size) has a dramatic influence on prediction
      performance. Though the choice of image measurement and MVPA algorithm can impact
      the result, there was no universally optimal selection. Intriguingly, the choice
      of algorithm seemed to be less critical than the choice of measurement type.
      Finally, our results showed that cross-validation estimates of performance, while
      generally optimistic, correlate well with generalization accuracy on a new
      dataset.

PMID- 25048628
TI  - Tumor heterogeneity at protein level as an independent prognostic factor in
      endometrial cancer.
AB  - Intratumor heterogeneity implies heterogeneous protein function, facilitating
      tumor adaptation which results in therapeutic failure. We hypothesized that tumor
      heterogeneity at protein level may influence the course of the disease. As a
      single biopsy might not represent the full biologic complexity of the tumor, we
      have analyzed immunohistochemically four different cores obtained from each
      primary tumor within the cohort of 364 patients with endometrial cancer (EC). The
      following proteins were examined: estrogen receptor 1 (ESR1), progesterone
      receptor, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia
      viral oncogene homolog 2, receptor tyrosine-protein kinase erbB-3, v-erb-b2 avian
      erythroblastic leukemia viral oncogene homolog 4, phosphatidylinositol-4,5
      bisphosphate 3-kinase, phosphorylated v-akt murine thymoma viral oncogene homolog
      1, v-myc avian myelocytomatosis viral oncogene homolog, DNA topoisomerase II
      alpha 170 kDa (TOP2A), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor
      protein p53, RAD21 homolog, S. pombe, and runt-related transcription factor 1.
      Particularly strong correlation was found between TOP2A and CDKN2A heterogeneity
      and higher stage of the disease (P = .0002 and P = .0003, respectively). Most
      correlations with clinicopathologic data were observed for ESR1 heterogeneity
      that correlated with non-endometrioid carcinomas (P=.02), higher stage (P=.005),
      grade (P=.01), and the presence of metastases (P = .01). Thirty-nine (11.0%)
      patients were classified as "globally heterogeneous". Cumulative tumor
      heterogeneity strongly correlated with the presence of metastases, higher stage,
      and higher grade of the disease (all P b .05). It also carried negative
      prognostic value (P=.0008). We show that the degree of heterogeneity in EC might
      serve as a clinically valid molecular marker. 

PMID- 25048629
TI  - Emerging approaches to target tumor metabolism.
AB  - Therapeutic exploitation of the next generation of drugs targeting the genetic
      basis of cancer will require an understanding of how cancer genes regulate tumor
      biology. Reprogramming of tumor metabolism has been linked with activation of
      oncogenes and inactivation of tumor suppressors. Well established and emerging
      cancer genes such as MYC, IDH1/2 and KEAP1 regulate tumor metabolism opening up
      opportunities to evaluate metabolic pathway inhibition as a therapeutic strategy
      in these tumors. 

PMID- 25048631
TI  - Transesophageal pulmonary nodule biopsy using endoscopic ultrasonography.
AB  - OBJECTIVE: Parenchymal pulmonary nodules located in proximity to the mediastinum,
      vertebral column, major vessels, or behind the heart can be technically
      challenging and dangerous to biopsy using traditional image-guided techniques.
      Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) can be used to
      access some of these difficult to reach lesions. The purpose of the present study
      was to report our experience with this technique in a consecutive cohort of
      selected patients. METHODS: This was a retrospective cohort study. Eligible
      patients were identified from a prospective database. A transesophageal approach
      under real-time EUS guidance was performed using a 22-gauge needle. All patients
      underwent postprocedural chest radiography and were followed up at 30 days.
      RESULTS: During a 31-month period, 55 patients underwent EUS-guided lung biopsy.
      Confirmatory visual correlation of nodule localization within the lung parenchyma
      between computed tomography and EUS was possible in 100% of cases. The lung
      nodule distribution was 41.5% right upper lung, 18.9% right lower lung, 28.3%
      left upper lung, and 11.3% left lower lung. Histologic and cytologic sampling was
      adequate in 52 of the 55 procedures (94.5%). In all patients with adequate biopsy
      sampling, accurate pathocytologic diagnoses of the target parenchymal nodules
      were obtained. The accuracy and sensitivity of EUS-FNA were both 94.5% and
      consistent with the diagnosis on pathologic resection or clinical progression of
      disease, or both. No morbidity resulted from the procedure nor was observed at 30
      days. CONCLUSIONS: EUS-FNA of parenchymal pulmonary nodules is safe and accurate
      and allows for biopsy of perimediastinal lung lesions not attainable using
      traditional techniques.

PMID- 25048633
TI  - Mitral valve repair rates correlate with surgeon and institutional experience.
AB  - OBJECTIVES: Mitral valve (MV) repair rates have lagged despite reported superior
      outcomes in patients with mitral regurgitation. The purpose of the present study
      was to evaluate the relationship between procedure volume and the propensity for
      MV repair in a multi-institution, regional patient cohort. METHODS: Society of
      Thoracic Surgeons-certified patient records of those undergoing MV repair or MV
      replacement (MVR) for moderate or severe mitral regurgitation were evaluated from
      17 different centers (2001-2011). The relationship between the annual hospital
      and surgeon volume and the propensity for MV repair over MVR was analyzed using
      multivariable, mortality risk-adjusted models with restricted cubic splines.
      RESULTS: A total of 4194 patients were evaluated (MV repair, 2516; MVR, 1662).
      The median annual mitral procedure volume was 54 operations for hospitals and 13
      operations for surgeons. The overall MV repair rate was 60%, with significant
      variations among hospitals (range, 35%-70%) and surgeons (range, 0%-90%). The MVR
      patients presented with higher Society of Thoracic Surgeons Predicted Risk of
      Mortality scores (6% vs 2%, P < .001). After adjustment for Predicted Risk of
      Mortality score, both annual hospital (P = .04) and surgeon (P < .0001) procedure
      volume were associated with the probability of MV repair. The likelihood for MV
      repair correlated with an operative volume of >= 20 procedures annually. Among
      surgeons and hospitals performing >= 20 mitral operations annually, MV repair
      rates were greater (73% vs 26% and 62% vs 37%, respectively, P < .001 for both).
      CONCLUSIONS: Significant variation in the performance of MV repair over MVR for
      mitral regurgitation persists in the modern surgical era. Average annual surgeon
      volume was more significantly associated with MV repair rate than institutional
      volume, with an increased likelihood for performance of MV repair among surgeons
      performing >20 procedures annually. In the upcoming era of percutaneous MV
      repair, surgeon volume and expertise as a gatekeeper should dictate access to
      this technology and the decisions for the best approach to MV repair.

PMID- 25048635
TI  - A minimally invasive Cox maze IV procedure is as effective as sternotomy while
      decreasing major morbidity and hospital stay.
AB  - OBJECTIVES: The Cox maze IV procedure has the best results for the surgical
      treatment of atrial fibrillation. It has been traditionally performed through
      sternotomy with excellent outcomes, but this has been considered to be too
      invasive. An alternative approach is to perform a less invasive right
      anterolateral minithoracotomy. This series compared these approaches at a single
      center in consecutive patients. METHODS: Patients undergoing a Cox maze IV
      procedure (n = 356) were retrospectively reviewed from January 2002 to February
      2014. Patients were stratified into 2 groups: right minithoracotomy (RMT; n =
      104) and sternotomy (ST; n = 252). Preoperative and perioperative variables were
      compared as well as long-term outcomes. Patients were followed up for 2 years and
      rhythm was confirmed with an electrocardiogram or prolonged monitoring. RESULTS:
      Freedom from atrial tachyarrhythmias off antiarrhythmic drugs was 81% and 74% at
      1 and 2 years, respectively, using an RMT approach and was not significantly
      different from the ST group at these same time points. The overall complication
      rate was lower in the RMT group (6% vs 13%, P = .044) as was 30-day morality (0%
      vs 4%, P = .039). Median length of stay in the intensive care unit was lower in
      the RMT group than in the ST group (2 days [range, 0-21 days] vs 3 days [range, 1
      61 days]; P = .004) as was median hospital length of stay (7 days [range, 4-35
      days] vs 9 days [range, 1-111 days]; P < .001). CONCLUSIONS: The Cox maze IV
      procedure performed through a right minithoracotomy is as effective as sternotomy
      in the treatment of atrial fibrillation. This approach was associated with fewer
      complications, decreased mortality and decreased length of stay in the intensive
      care unit and hospital length of stay.

PMID- 25048636
TI  - Preclinical studies of pegylated- and non-pegylated liposomal forms of
      doxorubicin as radiosensitizer on orthotopic high-grade glioma xenografts.
AB  - PURPOSE: Free doxorubicin (DXR) is not currently used to treat brain tumors
      because (i) the blood-brain barrier limits the drug deposition into the brain
      (ii) lethal toxic effects occur when combined with radiation therapy. Since
      encapsulation of DXR within liposomal carriers could overcome these drawbacks,
      the present study aimed at evaluating the radiosensitizing properties of non
      pegylated (NPL-DXR) and pegylated (PL-DXR) liposomal doxorubicin on orthotopic
      high-grade glioma xenografts (U87). METHODS: DXR accumulation in brain tissues
      was assessed by a high-performance liquid chromatography method and antitumor
      efficacy was evaluated by mice survival determination. RESULTS: We showed that
      encapsulation of DXR ensured a preferential deposition of DXR in tumoral tissue
      in comparison with normal brain tissue: the best AUC tumor tissue/AUC normal
      tissue ratio depended greatly on the schedule. Overall, thanks to the
      optimization of the delivery schedule, we demonstrated a radiosensitizing effect
      for both liposomal DXR without toxicity of this combination on the U87 human
      malignant glioma orthotopic xenografts. CONCLUSION: This study shows that the use
      of nanocarriers, allowing targeting of intracerebral tumor, renders relevant the
      combination of anthracyclin with radiation therapy to treat brain tumors, opening
      a new field of therapeutic applications. However, our results point out that, for
      each new delivery system, the administration schedules need to be rigorously
      optimized.

PMID- 25048637
TI  - Physiology-based IVIVE predictions of tramadol from in vitro metabolism data.
AB  - PURPOSE: To predict the tramadol in vivo pharmacokinetics in adults by using in
      vitro metabolism data and an in vitro-in vivo extrapolation (IVIVE)-linked
      physiologically-based pharmacokinetic (PBPK) modeling and simulation approach
      (Simcyp(r)). METHODS: Tramadol metabolism data was gathered using metabolite
      formation in human liver microsomes (HLM) and recombinant enzyme systems (rCYP).
      Hepatic intrinsic clearance (CLintH) was (i) estimated from HLM corrected for
      specific CYP450 contributions from a chemical inhibition assay (model 1); (ii)
      obtained in rCYP and corrected for specific CYP450 contributions by study
      specific intersystem extrapolation factor (ISEF) values (model 2); and (iii)
      scaled back from in vivo observed clearance values (model 3). The model-predicted
      clearances of these three models were evaluated against observed clearance values
      in terms of relative difference of their geometric means, the fold difference of
      their coefficients of variation, and relative CYP2D6 contribution. RESULTS: Model
      1 underpredicted, while model 2 overpredicted the total tramadol clearance by -27
      and +22%, respectively. The CYP2D6 contribution was underestimated in both models
      1 and 2. Also, the variability on the clearance of those models was slightly
      underpredicted. Additionally, blood-to-plasma ratio and hepatic uptake factor
      were identified as most influential factors in the prediction of the hepatic
      clearance using a sensitivity analysis. CONCLUSION: IVIVE-PBPK proved to be a
      useful tool in combining tramadol's low turnover in vitro metabolism data with
      system-specific physiological information to come up with reliable PK predictions
      in adults.

PMID- 25048638
TI  - The arginine deiminase pathway of koji bacteria is involved in ethyl carbamate
      precursor production in soy sauce.
AB  - Ethyl carbamate (EC) is a group 2A carcinogen generated from a few precursors in
      many fermented foods and alcoholic beverages. Citrulline, urea, carbamoyl
      phosphate, and ethanol are common precursors detected in fermented foods. In this
      study, citrulline was proved to be the main EC precursor in soy sauce, which was
      found to be accumulated in moromi mash period and correlated with the utilization
      of arginine by koji bacteria. Six koji isolates belonging to three genera were
      identified to be able to accumulate citrulline via the arginine deiminase (ADI)
      pathway. Among these strains, only Pediococcus acidilactici retained high
      activities in synthesis and accumulation of citrulline in the presence of high
      concentration of sodium chloride. These results suggested that P. acidilactici is
      responsible for the accumulation of citrulline, one of the EC precursors, in the
      process of soy sauce fermentation. 

PMID- 25048639
TI  - A novel device for resistance-free biomechanical testing of the metaphysis of
      long bones.
AB  - BACKGROUND: Biomechanical testing is an essential component of bone research. In
      order to test the metaphyseal region of long bones, a typical location for the
      nowadays increasing field of osteoporotic bone changes, three-point bending and
      breaking test devices are suitable and widely used. The aim of our study was to
      increase the effectiveness of this method by using a newly developed ball-mounted
      platform design. This new design eliminates the negative effects of friction,
      present in previous studies, caused by the lengthening of the distal tibia along
      its diaphyseal axis while sliding over the surface of a fixed aluminum block.
      METHODS: 70 tibiae of 35 twelve week old, female Sprague Dawley rats were
      separated into two groups for a metaphyseal bending/breaking test. Group 1 was
      made up of the rat's right tibiae, Group 2 of the left tibiae. Group 1 was tested
      on a solid metal block according to previously established testing devices
      whereas Group 2 was tested on the newly designed device: the resistance-free
      gliding, ball-mounted platform. Stiffness (N/mm), yield Load (N), and failure
      Load (N) were registered. In the evaluation of both testing procedures, the
      results of the right and left tibiae were compared according to the rat they
      originated from. RESULTS: Stiffness (S) showed highly significant differences (p
      = 0.002) with 202.25 +/- 27.010 N/mm SD (Group 1) and 184.66 +/- 35.875 N/mm SD
      (Group 2). Yield Load (yL) showed highly significant differences (p < 0.001) with
      55.31 +/- 13.074 N SD (Group1) and 37.17 +/- 12.464 N SD (Group2). The mean
      failure Load (fL) did not differ significantly (p < 0.231) between Group 1: 81.34
      +/- 11.972 N SD and Group 2: 79.63 +/- 10.345 N SD. CONCLUSIONS: We therefore
      conclude that, used in the three-point bending/breaking test, the mobile, ball
      mounted platform device is able to efficiently eliminate the influence of
      friction in terms of stiffness and yield load. Failure Load was not affected. We
      suggest that the new ball-mounted platform device, when compared to other
      existing techniques, generates more accurate test results when used in the three
      point bending/breaking test of the metaphysis of long bones.

PMID- 25048640
TI  - Self-Employment and Health: Barriers or Benefits?
AB  - The self-employed are often reported to be healthier than wageworkers; however,
      the cause of this health difference is largely unknown. The longitudinal nature
      of the US Health and Retirement Study allows us to gauge the plausibility of two
      competing explanations for this difference: a contextual effect of self
      employment on health (benefit effect), or a health-related selection of
      individuals into self-employment (barrier effect). Our main finding is that the
      selection of comparatively healthier individuals into self-employment accounts
      for the positive cross-sectional difference. The results rule out a positive
      contextual effect of self-employment on health, and we present tentative evidence
      that, if anything, engaging in self-employment is bad for one's health. Given the
      importance of the self-employed in the economy, these findings contribute to our
      understanding of the vitality of the labor force. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 25048641
TI  - Are all multisubunit tethering complexes bona fide tethers?
AB  - Since the late 1990s, a number of multisubunit tethering complexes (MTCs) have
      been described that function in membrane trafficking events: TRAPP I, TRAPP II,
      TRAPP III, COG, HOPS, CORVET, Dsl1, GARP and exocyst. On the basis of structural
      and sequence similarities, they have been categorized as complexes associated
      with tethering containing helical rods (CATCHR) (Dsl1, COG, GARP and exocyst) or
      non-CATCHR (TRAPP I, II and III, HOPS and CORVET) complexes (Yu IM, Hughson FM.
      Tethering factors as organizers of intracellular vesicular traffic. Annu Rev Cell
      Dev Biol 2010;26:137-156). Both acronyms (CATCHR and MTC) imply these complexes
      tether opposing membranes to facilitate fusion. The main question we will address
      is: have these complexes been formally demonstrated to function as tethers? If
      the answer is no, then is it premature or even correct to refer to them as
      tethers? In this commentary, we will argue that the vast majority of MTCs have
      not been demonstrated to act as a tether. We propose that a distinction between
      the terms tether and tethering factor be considered to address this issue. 

PMID- 25048642
TI  - On the usability of intramuscular EMG for prosthetic control: a Fitts' Law
      approach.
AB  - Previous studies on intramuscular EMG based control used offline data analysis.
      The current study investigates the usability of intramuscular EMG in two degree
      of-freedom using a Fitts' Law approach by combining classification and
      proportional control to perform a task, with real time feedback of user
      performance. Nine able-bodied subjects participated in the study. Intramuscular
      and surface EMG signals were recorded concurrently from the right forearm. Five
      performance metrics (Throughput,Path efficiency, Average Speed, Overshoot and
      Completion Rate) were used for quantification of usability. Intramuscular EMG
      based control performed significantly better than surface EMG for Path Efficiency
      (80.5+/-2.4% vs. 71.5+/-3.8%, P=0.004) and Overshoot (22.0+/-3.0% vs. 45.1+/
      6.6%, P=0.01). No difference was found between Throughput and Completion Rate.
      However the Average Speed was significantly higher for surface (51.8+/-5.5%) than
      for intramuscular EMG (35.7+/-2.7%). The results obtained in this study imply
      that intramuscular EMG has great potential as control source for advanced
      myoelectric prosthetic devices. 

PMID- 25048643
TI  - Comparison of the electromyographic activity of the anterior trunk during the
      execution of two Pilates exercises - teaser and longspine - for healthy people.
AB  - This study compared abdominal electromyographic (EMG) activity during the
      performance of Pilates' exercises. 16 females participated in the study. EMG
      signals of the rectus abdominis (RA) and external oblique (EO) were recorded
      during Longspine performed on the mat, Cadillac, and Reformer and the Teaser
      performed on the mat, Cadillac, and Combo-chair. Values were normalized by the
      EMG peak of a dynamic task and divided in concentric and eccentric phases.
      Longspine performed on the mat increased EO activity in the concentric phase more
      than on the Reformer and the Cadillac (Mean Difference (MD)=12.2%; 95% Confidence
      Interval (CI) [3.36; 21.04]; p=.04). Differences in the eccentric phase of the RA
      favored the mat compared to the Reformer (MD=5.20%; 95% CI [-0.55; 10.95];
      p=.02). Significant differences in eccentric contraction of the RA were found for
      teaser exercise performed on the mat versus Cadillac (MD=1.1%; 95% CI [-4.13;
      6.33]; p=.04) and the mat versus the Combo-chair (MD=6.3%; 95% CI [1.31; 11.29];
      p=.005). Higher concentric activation values for the EO were found when the
      teaser exercise was performed on the Cadillac. Exercises performed on the mat
      required greater rectus abdominis activation. 

PMID- 25048644
TI  - LRRK2-G2019S mutation is not associated with an increased cancer risk: a kin
      cohort study.

PMID- 25048645
TI  - Meeting the challenge of intermolecular gold(I)-catalyzed cycloadditions of
      alkynes and allenes.
AB  - The development of gold(I)-catalyzed intermolecular carbo- and hetero
      cycloadditions of alkynes and allenes has been more challenging than their
      intramolecular counterparts. Here we review, with a mechanistic perspective, the
      most fundamental intermolecular cycloadditions of alkynes and allenes with
      alkenes. 

PMID- 25048646
TI  - Use of nondrug, nonoperative interventions by community-dwelling people with hip
      and knee osteoarthritis.
AB  - OBJECTIVE: Guidelines recommend nondrug, nonoperative treatments as the first
      line approach for hip and knee osteoarthritis (OA), yet there is limited data
      regarding use of these treatments in OA. This study describes the use of nondrug,
      nonoperative interventions in people with hip and knee OA. METHODS: A convenience
      sample of 591 people with hip or knee OA completed a questionnaire indicating
      their past and/or current use of 17 nondrug, nonoperative interventions each for
      their hip or knee OA. Descriptive analyses, based on frequency counts and
      proportions, and chi-square tests described the use of each intervention in the
      total cohort, and within subgroups of knee and hip OA. RESULTS: Participants were
      currently using a mean +/- SD of 0.8 +/- 0.9 of the strongly recommended
      interventions. Making efforts to lose weight (50%, n = 294) and shoe orthoses
      (30%, n = 175) were the most common currently used interventions. Strengthening
      (26%, n = 152) and stretching exercises (23%, n = 133) were the most common
      interventions that participants had tried in the past but were no longer
      utilizing. Of note, 12% (n = 71) had never used any of the interventions. Use of
      5 treatments (shoe orthoses, heat and/or cold, muscle strengthening exercises,
      walking aids, and transcutaneous electrical nerve stimulation) was significantly
      different between the hip and knee cohorts (P < 0.05). CONCLUSION: Use of
      nondrug, nonoperative interventions was low among people with hip and knee OA.
      Our findings show evidence-practice gaps, particularly with respect to the
      interventions most strongly recommended in clinical guidelines for hip and knee
      OA (weight loss and exercise).

PMID- 25048647
TI  - [Management of peripheral facial nerve palsy in children].
AB  - Peripheral facial nerve palsy may (secondary) or may not have a detectable cause
      (idiopathic facial palsy or Bell's palsy). Idiopathic facial palsy is the common
      form of facial palsy. It remains diagnosis by exclusion. The prognosis is more
      favourable in children than in adults. We present current diagnostic procedures
      and recommendations regarding treatment in children. 

PMID- 25048648
TI  - [Evaluation of the impact and efficiency of high-fidelity simulation for neonatal
      resuscitation in midwifery education].
AB  - BACKGROUND: Prompt initiation of appropriate neonatal resuscitation skills is
      critical for the neonate experiencing difficulty transitioning to extra-uterine
      life. Expertise in neonatal resuscitation is essential for personnel involved in
      the care of newborns, above all for midwives who are sometimes alone to initiate
      the first resuscitation. The use of simulation training is considered to be an
      indispensable tool to address these challenges, not only in continuing education
      but also in midwifery education. OBJECTIVE: The aim of this study was to evaluate
      the impact and efficiency of high-fidelity simulation for neonatal resuscitation
      in midwifery education. METHODS: This was a prospective monocentric study
      conducted in the Angers university hospital between October and December 2012 and
      included two groups of midwifery students (n=40) who received high-fidelity
      simulation as part of their basic midwifery education. Participants' perceptions
      of the knowledge, skills, and confidence gained following training in high
      fidelity simulation for neonatal resuscitation were determined using a pre-/post
      test questionnaire design completed during the training and also several months
      after the course, as well as after the students had begun working. A satisfaction
      survey to evaluate this training was also completed at the same time. RESULTS:
      With a good participation rate (67.5%), the survey showed a high degree of
      satisfaction among the participants. This training was described as facilitating
      their hire in one third of cases. A significant increase in self-assessment of
      skills scores was observed between the pre-test and post-test (P<0.001), the pre
      test and the distance test (P<0.001), and the post-test and distance test
      (P=0.007). Although a decrease in the median score was observed on the knowledge
      questionnaire given as a post-test, this median remained significantly higher
      than that obtained on the pre-test (P=0.03). CONCLUSION: The significant
      improvement in knowledge during the session and its preservation after a few
      months confirmed the efficacy of this teaching method. The simulation training
      increased the participants' perceptions of their knowledge, skills, and
      confidence in conducting neonatal resuscitation. These preliminary results are
      very encouraging and argue in favor of generalizing this teaching method.
      However, this training could be more profitable if it was proposed earlier in the
      midwifery curriculum and organized with a multidisciplinary team (pediatric and
      anesthesia residents).

PMID- 25048649
TI  - [Placental mesenchymal dysplasia: consequences for the newborn].
AB  - CASE REPORT: We report the case of a newborn presenting with anemia,
      thrombopenia, intrauterine growth restriction (IUGR), and hepatic hemangioma
      revealing placental mesenchymal dysplasia. CONCLUSION: This rare disease is not
      always diagnosed during pregnancy. Placental chorioangioma is responsible (in the
      absence of lethal complications in utero) for IUGR, anemia, neonatal
      thrombopenia, and hepatic or cutaneous hemangiomas. The early search for
      hemangiomas with ultrasound scanning could be useful to predict cardiac failure
      by left-to-right shunt.

PMID- 25048650
TI  - Neglected areas of psychiatric practice and research.

PMID- 25048651
TI  - Are 'buy-polar' forces and 'try-polar' thinking expanding bipolarity?

PMID- 25048652
TI  - The departure of hypochondriasis is no loss.

PMID- 25048653
TI  - Response to Fergusson and Boden: The psychological impact of major disasters.

PMID- 25048654
TI  - DevR (DosR) mimetic peptides impair transcriptional regulation and survival of
      Mycobacterium tuberculosis under hypoxia by inhibiting the autokinase activity of
      DevS sensor kinase.
AB  - BACKGROUND: Two-component systems have emerged as compelling targets for
      antibacterial drug design for a number of reasons including the distinct
      histidine phosphorylation property of their constituent sensor kinases. The DevR
      DevS/DosT two component system of Mycobacterium tuberculosis (M. tb) is essential
      for survival under hypoxia, a stress associated with dormancy development in
      vivo. In the present study a combinatorial peptide phage display library was
      screened for DevS histidine kinase interacting peptides with the aim of isolating
      inhibitors of DevR-DevS signaling. RESULTS: DevS binding peptides were identified
      from a phage display library after three rounds of panning using DevS as bait.
      The peptides showed sequence similarity with conserved residues in the N-terminal
      domain of DevR and suggested that they may represent interacting surfaces between
      DevS and DevR. Two DevR mimetic peptides were found to specifically inhibit DevR
      dependent transcriptional activity and restrict the hypoxic survival of M. tb.
      The mechanism of peptide action is majorly attributed to an inhibition of DevS
      autokinase activity. CONCLUSIONS: These findings demonstrate that DevR mimetic
      peptides impede DevS activation and that intercepting DevS activation at an early
      step in the signaling cascade impairs M. tb survival in a hypoxia persistence
      model.

PMID- 25048655
TI  - Clinical results with Jarvik 2000 axial flow left ventricular assist device:
      Osaka University Experience.
AB  - The aim of this study was to evaluate our clinical experience with the Jarvik
      2000 axial flow pump (Jarvik Heart, Inc, New York, NY, USA), a miniature axial
      flow left ventricular assist device (LVAD). The clinical results of eight
      patients, who underwent LVAD implantation with the Jarvik 2000 (median age 55.0
      years; six men) between 2005 and 2010, including two who participated in a
      multicenter clinical trial in Japan, were reviewed. Two patients underwent LVAD
      implantation as destination therapy. Four patients underwent Jarvik 2000
      implantation via median sternotomy, while the other four underwent implantation
      via left thoracotomy. There were no major complications during surgery. Four
      patients were supported for more than 2 years. The longest support duration was
      1,618 days. Six patients successfully bridged to heart transplantation after a
      median 725 days of support. One patient on destination therapy died of a cerebral
      infarction. The other patient on destination therapy had had the LVAD for 1,618
      days. The overall survival rates at 1, 2, and 3 years were 100, 86, and 86%,
      respectively. The median postoperative serum lactate dehydrogenase level was
      860.5 U/L at 1 month, 735 U/L at 6 months, and 692 U/L at 1 year. There were no
      fatal device-related infections. We found that the Jarvik 2000 with pin bearing
      could support patients with end-stage heart failure with acceptable mortality and
      morbidity rates. Further evaluations of the prevalence of thromboembolic and
      hemolytic events in patients with the new conical-bearing Jarvik 2000 are
      required.

PMID- 25048656
TI  - Upper limb vascular occlusion in the recipient of a monochorionic twin pair.
AB  - Monochorionicity is responsible for an increased rate of severe complications
      because of unequal splitting of the placental mass and/or an imbalance in the
      blood flow across placental vascular anastomoses. Vascular limb occlusion is one
      of the rare complications of monochorionic twins, usually occurring in the lower
      extremities after intra-uterine death of one twin, antenatal intervention (amnio
      reduction or laser therapy) or in the presence of twin anemia-polycythemia
      syndrome. We report a case of vascular occlusion of the upper extremity in the
      recipient twin of a monochorionic pair in the absence of those predisposing
      factors. 

PMID- 25048658
TI  - Multiple sclerosis: KIR4.1 as an autoantigen in MS--new questions raised.

PMID- 25048659
TI  - Multiple sclerosis: Spinal cord MRI reveals progression-related MS pathology.

PMID- 25048667
TI  - Placental immune response to apple allergen in allergic mothers.
AB  - The immunological milieu in the placenta may be crucial for priming the
      developing foetal immune system. Early imbalances may promote the establishment
      of immune-mediated diseases in later life, including allergies. The initial
      exposure to allergens seems to occur in utero, but little is known about allergen
      induced placental cytokine and chemokine release. The release of several
      cytokines and chemokines from placenta tissue after exposure to mast cell
      degranulator compound 48/80 or apple allergen in placentas from allergic and
      healthy mothers was to be analysed. Four placentas from women with apple allergy
      and three controls were applied in a placental perfusion model with two separate
      cotyledons simultaneously perfused with and without apple allergen (Mal d 1). Two
      control placentas were perfused with compound 48/80. In outflow, histamine was
      quantified spectrophotofluorometrically, IL-2, IL-4, IL-6, IL-10, TNF and IFN
      gamma by a cytometric multiplex bead array and IL-13 and CXCL10, CXCL11, CCL17
      and CCL22 with an in-house multiplex Luminex assay. Compound 48/80 induced a
      rapid release of histamine, CXCL10, CXCL11, CCL17 and CCL22, but not of the other
      factors. Apple allergen induced a time-dependent release of IL-6 and TNF, but not
      of histamine, in placentas of women with apple allergy compared with the
      unstimulated cotyledon. CCL17 levels were slightly increased after allergen
      stimulation in control placentas. Allergens can induce placental cytokines and
      chemokines distinctly in allergic and healthy mothers. These mediators may affect
      the prenatal development of the immune system and modify the risk of diseases
      related to immune disorders in childhood such as allergies. 

PMID- 25048668
TI  - Effects of extra school-based physical education on overall physical fitness
      development--the CHAMPS study DK.
AB  - First, this study aimed to investigate if four extra physical education (PE)
      lessons per week improved children's development in physical fitness. Second, to
      investigate if the extra PE lessons improved development in physical fitness for
      children with lower levels of fitness at baseline. This study was a longitudinal
      controlled school-based study. The study population consisted of 10 Danish public
      schools with children in preschool to fourth grade (cohorts 0-4) with 2.5-year
      follow-up. Six schools had extra PE and four schools had normal PE. In total 1247
      children were included (normal PE = 536, extra PE = 711). Development in fitness
      was analyzed using a composite z-score from six fitness tests. Multilevel mixed
      effects linear regression was used to examine the association between school type
      and development in fitness. Extra PE increased the total development of composite
      z-score units among children enrolled in cohort 4 and borderline in cohort 3 with
      1.06 (95% confidence interval 0.48-1.65) and 0.52 z-score units (-0.06 to 1.09),
      respectively. Children in the lower 50 percentiles increased their development
      with 0.47 (0.08-0.85) z-score units. Extra PE in schools improved development in
      fitness for cohort 4 and borderline for cohort 3 among all children. Extra PE
      improved fitness development across all cohorts among children with low fitness
      levels. 

PMID- 25048670
TI  - PDT experience in Brazil: A regional profile.
AB  - The success of PDT and its establishment into the existent hall of therapeutic
      modalities depends on the collection of reported experiences from around the
      world. In that sense, it is important to report approaches taken by different
      countries and what their views are on the future of PDT. Following this idea, we
      present our clinical experience in photodynamic therapy (PDT) in Brazil, as well
      as the experimental advances coming up in parallel with clinical implementation.
      This report is a consequence of pioneering work in a collaborative program
      involving the Physics Institute in Sao Carlos, Sao Paulo State (SP), Brazil, the
      Medical School of the University of Sao Paulo, Ribeirao Preto, SP, Brazil and the
      Cancer Hospital Amaral Carvalho, Jau, SP, Brazil. This collaborative program,
      begun in 1997, with the first patient treated in 1999, has treated over 400
      patients by late 2004. About 80% of lesions were located in the head and neck or
      skin, but experience is being built in esophagus, bladder, gynecology, and
      cutaneous recurrence of breast cancer, among others. The overall results have
      shown to be compatible with previously reported data. Modifications, whose goal
      is to improve patient benefit and optimize results, are being implemented as we
      gain experience. In parallel with the clinical development, several laboratories
      have started studying experimental whose purpose is to analyze the clinical
      results and to contribute to the worldwide effort to bring PDT to the forefront
      of therapies offered to patients. We present the overall results of our 5 years
      experience as well as the whole implementation process. 

PMID- 25048671
TI  - Photopheresis up-regulates CD36 on monocytes and reduces CD25(+) and CD28(+) T
      cell numbers.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment for some
      malignant T cell proliferations and disorders associated with pathogenic T cell
      activation. ECP induces apoptosis in lymphocytes and up-regulates the antigen
      processing ability of monocytes. Recently, it has been proposed that the anti
      tumour response, generated by ECP, can be enhanced by prolonging the co-culture
      of the ECP-treated lymphocytes and monocytes prior to re-infusion. However, early
      markers of lymphoid apoptosis and changes in cytokine secretion have been
      observed immediately following ECP. This study aimed to determine the rapid
      effects of ECP on significant markers associated with antigen presentation.
      METHODS: Pre- and post-ECP samples, from 11 chronic graft versus host disease
      (cGvHD) and 3 cutaneous T cell lymphoma (CTCL) patients, were tested. The
      monocytes were evaluated for CD36 and CD91 expression, whilst the number of T
      cells positive for CD25, CD28, CD62L, CD152 and CD154 were determined. The pre-
      and post-ECP samples were compared statistically to determine change and both pre
      and post-samples were compared to age/sex-matched controls. RESULTS: Monocyte
      expression of CD36 increased to normal immediately post-ECP in both patient
      groups, whilst the percentage of CD25(+) and CD28(+) T cells fell significantly
      in the cGvHD cohort following ECP. CONCLUSION: CD36 is an important receptor for
      the uptake of apoptotic material and its up-regulation would be beneficial in the
      antigen-processing mechanism proposed for ECP. No enhancement in markers of T
      cell activation would indicate that ECP-treated lymphocytes play no direct role
      in the proposed cytotoxic response. However, reduction in CD25 and CD28 may
      represent a mechanism beneficial in disease states with excess T cell activation.

PMID- 25048669
TI  - Mechanisms in photodynamic therapy: Part three-Photosensitizer pharmacokinetics,
      biodistribution, tumor localization and modes of tumor destruction.
AB  - Photodynamic therapy (PDT) has been known for over a hundred years, but is only
      now becoming widely used. Originally developed as cancer therapy, some of its
      most successful applications are for non-malignant disease. The majority of
      mechanistic research into PDT, however, is still directed towards anti-cancer
      applications. In the final part of series of three reviews, we will cover the
      possible reasons for the well-known tumor localizing properties of
      photosensitizers (PS). When PS are injected into the bloodstream they bind to
      various serum proteins and this can affect their phamacokinetics and
      biodistribution. Different PS can have very different pharmacokinetics and this
      can directly affect the illumination parameters. Intravenously injected PS
      undergo a transition from being bound to serum proteins, then bound to
      endothelial cells, then bound to the adventitia of the vessels, then bound either
      to the extracellular matrix or to the cells within the tumor, and finally to
      being cleared from the tumor by lymphatics or blood vessels, and excreted either
      by the kidneys or the liver. The effect of PDT on the tumor largely depends at
      which stage of this continuous process light is delivered. The anti-tumor effects
      of PDT are divided into three main mechanisms. Powerful anti-vascular effects can
      lead to thrombosis and hemorrhage in tumor blood vessels that subsequently lead
      to tumor death via deprivation of oxygen and nutrients. Direct tumor cell death
      by apoptosis or necrosis can occur if the PS has been allowed to be taken up by
      tumor cells. Finally the acute inflammation and release of cytokines and stress
      response proteins induced in the tumor by PDT can lead to an influx of leukocytes
      that can both contribute to tumor destruction as well as to stimulate the immune
      system to recognize and destroy tumor cells even at distant locations. 

PMID- 25048672
TI  - Formation of protoporphyrin IX from carboxylic- and amino-derivatives of 5
      aminolevulinic acid.
AB  - BACKGROUND: Stability of ALA is an important factor for photodynamic therapy
      (PDT). The dimerization of ALA to pyrazines takes place via the amine group. It
      is, therefore, to be expected that blocking this group by addition of a formyl
      group should result in a more stable compound. METHODS: The ability of a new N
      formyl derivative of ALA (N-f-ALA) to form protoporphyrin IX (PPIX) was compared
      with that of ALA and three of its ester (methyl, butyl and hexyl) derivatives.
      Dark toxicity of the compounds was measured using MTT assay. Formation of PPIX
      was measured by fluorescence spectroscopy. RESULTS AND CONCLUSIONS: N-f-ALA
      showed an outstanding stability in water solutions even at pH 7. However, it
      induced no PPIX neither in WiDr cells in vitro, nor in mouse skin in vivo. A
      probable reason is lack of an enzyme that can cleave the bond between the formyl
      group and ALA. Thus, steric hindrance may prevent processing of the compound into
      porphobilinogen. N-f-ALA did not inhibit PpIX formation from ALA and is unable to
      enter the heme cycle. Generation of ALA from its derivatives, therefore, seems to
      be an essential step in PPIX synthesis.

PMID- 25048673
TI  - Photodynamic therapy in the management of malignant pleural mesothelioma: A
      review.
AB  - BACKGROUND: In the past decade there have been sporadic publications on malignant
      pleural mesothelioma (MPM). In the present trend of multi-modal treatment for MPM
      we aim to evaluate the current status of photodynamic therapy (PDT) in the
      management of MPM through a review study. METHODS: Original publications in
      English were the main source of the review and their material analysed in respect
      of patient and disease characteristics, PDT methods, mortality and morbidity and
      survival. Ten articles concerned with 230 patients were analysed and 35 other
      publications relevant to the study were used for reference. In every case PDT was
      used as an adjuvant to surgery whose role appeared to be a cyto-reductive
      procedure of debulking, pleurectomy and decortication (DPD) with/without
      pulmonary resection. PDT methods used two photosensitisers; PhotofrinTM [630nm
      laser light] (6 series=170 patients) or FoscanTM [652nm laser light] (4 series=60
      patients). RESULTS: Overall mortality and morbidity was 7.1% (4.9% for
      PhotofrinTM and 13.3% for FoscanTM PDT) and 48% (38% for PhotofrinTM and 70% for
      FoscanTM PDT) respectively. Better survival was achieved for DPD and early stage
      disease. CONCLUSIONS: Intra-operative (IOP) PDT in MPM is a safe procedure that
      requires more development and work regarding photosensitisers and light
      distribution systems for use in intra-pleural situations. The role of surgery in
      IOP-PDT appears to be cyto-reduction to <=5mm residual tumour thickness in order
      for PDT to be used effectively. Curative intent may depend on the stage of MPM
      and completeness of cyto-reduction with/without pulmonary resection.

PMID- 25048674
TI  - An ultrasound analysis of the response of Gorlin syndrome-related and sporadic
      basal cell carcinomas to aminolaevulinic acid photodynamic therapy.
AB  - BACKGROUND: Gorlin Syndrome (naevoid basal cell carcinoma syndrome, NBCCS)
      predisposes the patient to the development of basal cell carcinomas (BCCs)
      throughout their life. The standard treatment for isolated lesions is surgical
      excision. However, when numerous surgical procedures are required over time, the
      patient can be left with multiple disfiguring scars. Photodynamic therapy (PDT)
      offers a non-invasive treatment option for patients with this condition, in which
      ionizing radiation is contraindicated. This study evaluates PDT as a treatment
      modality for Gorlin Syndrome and compares the treatment response of Gorlin
      related basal cell carcinomas with that of the sporadic lesions. METHODS: In this
      un-randomized study, basal cell carcinomas in 25 Gorlin syndrome patients (with
      36 lesions) and 145 sporadic patients (with 189 lesions) were treated by
      photodynamic therapy, using delta-5-aminolaevulinic acid (ALA) as a
      photosensitizer and 100Jcm(-2) of red light (630+/-15nm). The maximum thickness
      of the BCC was measured by 20MHz pulsed ultrasound prior to treatment and again 4
      6 weeks and 12 months following treatment. The response of Gorlin syndrome
      lesions was compared to those in the overall sporadic population and then to a
      subpopulation matched as closely as possible for age, lesion thickness and site.
      RESULTS: For both populations, the average pre-treatment BCC thickness by US was
      1.5mm (overall range 0.3-5.3), and the average thickness at 4-6 weeks post
      treatment was 0.5mm (overall range 0-4.3). Those BCC less than 1.5mm thick prior
      to treatment were significantly more likely to have no US evidence of disease at
      4-6 weeks than and were more likely to be controlled at 12 months. CONCLUSIONS:
      The average response to ALA PDT of Gorlin syndrome-related BCC closely resembles
      that for the sporadic population, with the same wide range of responses for a
      given dose. Ultrasound parameters measured at treatment and at 4-6 weeks post
      treatment aid prediction of outcome and necessity for further treatment.

PMID- 25048675
TI  - Therapeutic effects of 5-ALA-induced photodynamic therapy in vulvar lichen
      sclerosus.
AB  - BACKGROUND: Lichen sclerosus (LS) is a rarely diagnosed, chronic inflammatory
      skin and mucosal condition. Its therapy is difficult and frequently not
      satisfactory. The data on photodynamic therapy (PDT) of vulva are promising but
      scanty. The aim of our study was to evaluate the therapeutic efficacy of
      photodynamic therapy in genital LS in women. METHODS: Twenty-four patients with
      clinical and histopathological diagnosis of lichen sclerosus accompanied with
      chronic vulvar itching, lasting between 3 months and 11 years, with human
      papillomavirus (HPV), bacterial and mycotic infections excluded, received three
      to six PDT cycles (180J, 700mW/cm(2)) in 14 days long intervals. Simultaneously
      they received no topical corticosteroids. Photodynamic diagnosis (PDD) was
      conducted prior to therapy and 4 weeks after its completion. RESULTS: In 17
      patients, the itching ceased completely, in 6 women it decreased, in 1 patient
      the itching continued, none of the patients presented exacerbation of itching.
      PDD after completion of therapy revealed in 10 patients normal, green
      fluorescence of vulva and in 14 women pathological, red fluorescence, usually
      fainter than before PDT. CONCLUSION: PDT is an effective therapeutic modality for
      chronic itching in lichen sclerosus.

PMID- 25048676
TI  - Therapeutic spectrum of nondigestible oligosaccharides: overview of current state
      and prospect.
AB  - Functional oligosaccharides have emerged as valuable components of food and
      dietary supplements. Their resistance to digestion and fermentation by colonic
      microbes has given them the nutritional edge. Apart from implications as dietary
      fibers, sweeteners, and humectants, they are hailed as prebiotics. Their
      beneficial effects extend from antioxidant, anti-inflammatory, immunomodulatory,
      antiallergic, hypotensive, hyperlipemic, neuroprotective to anticancer. The
      rising popularity of bioactive oligosaccharides has accelerated the search for
      their generation from new, sustainable sources. The surfacing crucial role in
      healthcare and unprecedented demand necessitates deeper investigation. The
      present review embodies an overview on various aspects of production, properties
      with emphasis on therapeutic applications of functional oligosaccharides. The
      biological efficacy and possible mechanisms of action of oligosaccharides have
      also been discussed. 

PMID- 25048677
TI  - Electroencephalographic evidence for a respiratory-related cortical activity
      specific of the preparation of prephonatory breaths.
AB  - Speech is a major disturbance to automatic breathing control. Speech occurs
      during exhalation, involving controlled inhibition of automatic inspiration.
      Additionally, utterances are preceded by prephonatory inspirations that must be
      prepared to account for prosody and loudness. We hypothesized that the speech
      related breathing control activities shaping prephonatory breaths originate in
      cortical pre-motor areas and should be associated with corresponding EEG
      evidence. We studied 10 normal subjects (4 men, age 23-27) during spontaneous
      breathing, sniff manoeuvres, and while reading out loud. Fronto-median
      inspiratory potentials (Cz EEG derivation) were consistently present before
      voluntary inspirations and large prephonatory breaths, while these potentials
      were generally absent during resting breathing or small prephonatory breaths. We
      conclude that the preparation of prephonatory breaths during speech has a
      cortical substrate, involving the cortical sources of premotor potentials. These
      results have important implications to validate whether co-modulation of the pre
      motor cortex and breathing during speech are incidental or whether these cortical
      modulations are necessary for initiation of "speech breathing". 

PMID- 25048678
TI  - Stress concentration around an atelectatic region: a finite element model.
AB  - Lung parenchyma surrounding an atelectatic region is thought to be subjected to
      increased stress compared with the rest of the lung. Using 37 hexagonal cells
      made of linear springs, Mead et al. (1970) measured a stress concentration
      greater than 30% in the springs surrounding a stiffer central cell. We re-examine
      the problem using a 2D finite element model of 500 cells made of thin filaments
      with a non-linear stress-strain relationship. We study the consequences of
      increasing the central stiff region from one to nine contiguous cells in regular
      hexagonal honeycombs and random Voronoi honeycombs. The honeycomb structures were
      uniformly expanded with strains of 15%, 30%, 45% and 55% above their resting, non
      deformed geometry. The curve of biaxial stress vs. fractional area change has a
      similar shape to that of the pressure-volume curve of the lung, showing an
      initial regime with relatively flat slope and a final regime with decreasing
      slope, tending toward an asymptote. Regular honeycombs had little variability in
      the maximum stress in radially oriented filaments adjacent to the central stiff
      region. In contrast, some filaments in random Voronoi honeycombs were subjected
      to stress concentration approximately 16 times the average stress concentration
      in the radially oriented filaments adjacent to the stiff region. These results
      may have implications in selecting the appropriate strategy for mechanical
      ventilation in ARDS and defining a "safe" level of alveolar pressure for
      ventilating atelectatic lungs. 

PMID- 25048679
TI  - Usefulness of serum bilirubin levels as a biomarker for long-term clinical
      outcomes after percutaneous coronary intervention.
AB  - The aim of this study was to evaluate the prognostic value of serum total
      bilirubin on the development of adverse outcomes after percutaneous coronary
      intervention (PCI) besides high-sensitivity cardiac troponin T (hs-cTnT) and N
      terminal pro-B type natriuretic peptide (NT-proBNP). Serum total bilirubin, hs
      cTnT, and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary
      endpoint was cardiac death. There were 21 events of cardiac death during a mean
      of 25.8 months of follow-up. When the serum total bilirubin cut-off level (median
      value) was set to 0.58 mg/dL using the receiver operating characteristic curve,
      the sensitivity was 95.2 % and the specificity was 51.0 % for differentiating
      between the group with cardiac death and the group without cardiac death. Kaplan
      Meier analysis revealed that the lower serum total bilirubin group (<0.58 mg/dL)
      had a significantly higher cardiac death rate than the higher serum total
      bilirubin group (>=0.58 mg/dL) (10.4 vs. 0.6 %, log-rank: P = 0.0001). In
      conclusion, low serum total bilirubin is a predictive marker for cardiac death
      after PCI.

PMID- 25048680
TI  - Is pentraxin 3 a biomarker, a player, or both in the context of coronary
      atherosclerosis and metabolic factors?
AB  - The objective of this study is to determine whether pentraxin-3 (PTX-3) is
      clinically a biomarker of inflammation, a player in anti-inflammation, or both
      with regard to coronary atherosclerosis, we compared levels of PTX-3 with levels
      of adiponectin in addition to high-sensitivity C-reactive protein (hs-CRP). We
      enrolled 693 patients (51 % male; mean age 64 +/- 12 years) at Fukuoka University
      Hospital. They were clinically suspected to have coronary artery disease (CAD) or
      had at least one cardiac risk factor and had undergone coronary computed
      tomography angiography (CTA). We evaluated the levels of PTX-3, hs-CRP, and
      adiponectin, the presence of CAD or metabolic factors, subcutaneous fat area,
      visceral fat area (VFA) and lipid profiles. The presence of CAD was independently
      associated with aging (p = 0.010) and the prevalence of hypertension (p <
      0.0001), but not the levels of PTX-3, hs-CRP and adiponectin by a multivariate
      analysis. Although the number of significantly stenosed coronary vessels (VD) was
      not associated with PTX-3 or adiponectin, hs-CRP tended to increase as the number
      of VD increased. In addition, PTX-3 decreased as the number of metabolic factors
      increased, whereas hs-CRP increased as the number of metabolic factors increased.
      Interestingly, PTX-3 did not correlate with hs-CRP, but was positively correlated
      with adiponectin. In a multiple regression analysis, adiponectin (p = 0.003) and
      VFA (p = 0.008) were significant predictors of PTX-3 levels. In conclusion, PTX-3
      and adiponectin showed similar associations with metabolic factors, whereas PTX-3
      and hs-CRP showed opposite trends. Adiponectin and VFA were significant
      predictors of PTX-3 levels. PTX-3 might have an atheroprotective role as well as
      serving as a simple biomarker, like adiponectin.

PMID- 25048681
TI  - Design method for multi-user workstations utilizing anthropometry and preference
      data.
AB  - Past efforts have been made to design single-user workstations to accommodate
      users' anthropometric and preference distributions. However, there is a lack of
      methods for designing workstations for group interaction. This paper introduces a
      method for sizing workstations to allow for a personal work area for each user
      and a shared space for adjacent users. We first create a virtual population with
      the same anthropometric and preference distributions as an intended demographic
      of college-aged students. Members of the virtual population are randomly paired
      to test if their extended reaches overlap but their normal reaches do not. This
      process is repeated in a Monte Carlo simulation to estimate the total percentage
      of groups in the population that will be accommodated for a workstation size. We
      apply our method to two test cases: in the first, we size polygonal workstations
      for two populations and, in the second, we dimension circular workstations for
      different group sizes. 

PMID- 25048683
TI  - The neocortex of cetartiodactyls. II. Neuronal morphology of the visual and motor
      cortices in the giraffe (Giraffa camelopardalis).
AB  - The present quantitative study extends our investigation of cetartiodactyls by
      exploring the neuronal morphology in the giraffe (Giraffa camelopardalis)
      neocortex. Here, we investigate giraffe primary visual and motor cortices from
      perfusion-fixed brains of three subadults stained with a modified rapid Golgi
      technique. Neurons (n = 244) were quantified on a computer-assisted microscopy
      system. Qualitatively, the giraffe neocortex contained an array of complex spiny
      neurons that included both "typical" pyramidal neuron morphology and "atypical"
      spiny neurons in terms of morphology and/or orientation. In general, the
      neocortex exhibited a vertical columnar organization of apical dendrites.
      Although there was no significant quantitative difference in dendritic complexity
      for pyramidal neurons between primary visual (n = 78) and motor cortices (n =
      65), there was a significant difference in dendritic spine density (motor cortex
      > visual cortex). The morphology of aspiny neurons in giraffes appeared to be
      similar to that of other eutherian mammals. For cross-species comparison of
      neuron morphology, giraffe pyramidal neurons were compared to those quantified
      with the same methodology in African elephants and some cetaceans (e.g.,
      bottlenose dolphin, minke whale, humpback whale). Across species, the giraffe
      (and cetaceans) exhibited less widely bifurcating apical dendrites compared to
      elephants. Quantitative dendritic measures revealed that the elephant and
      humpback whale had more extensive dendrites than giraffes, whereas the minke
      whale and bottlenose dolphin had less extensive dendritic arbors. Spine measures
      were highest in the giraffe, perhaps due to the high quality, perfusion fixation.
      The neuronal morphology in giraffe neocortex is thus generally consistent with
      what is known about other cetartiodactyls.

PMID- 25048682
TI  - Analgesic tolerance to morphine is regulated by PPARgamma.
AB  - BACKGROUND AND PURPOSE: Opioid drugs are potent analgesics. However, their
      chronic use leads to the rapid development of tolerance to their analgesic
      effects and subsequent increase of significant side effects, including drug
      dependence and addiction. Here, we investigated the role of PPARgamma in the
      development of analgesic tolerance to morphine in mice. EXPERIMENTAL APPROACH: We
      monitored analgesia on alternate days using the tail immersion test. KEY RESULTS:
      Daily administration of morphine (30 mg.kg(-1) , bid) resulted in the rapid
      development of tolerance to thermal analgesia. Co-administration of pioglitazone
      (10 and 30 mg.kg(-1) , bid) significantly attenuated the development and
      expression of tolerance. However, pretreatment with GW-9662 (5 mg.kg(-1) , bid),
      a selective PPARgamma antagonist, completely abolished this effect. Injection of
      GW-9662 and a lower dose of morphine (15 mg.kg(-1) , bid) accelerated the
      development of tolerance to its antinociceptive effect. Subsequently, we found
      that conditional neuronal PPARgamma knockout (KO) mice develop a more rapid and
      pronounced tolerance to morphine antinociception compared with wild-type (WT)
      controls. Moreover, in PPARgamma KO mice, pioglitazone was no longer able to
      prevent the development of morphine tolerance. CONCLUSIONS AND IMPLICATIONS:
      Overall, our results demonstrate that PPARgamma plays a tonic role in the
      modulation of morphine tolerance, and its pharmacological activation may help to
      reduce its development. These findings provide new information about the role of
      neuronal PPARgamma and suggest that combining PPARgamma agonists with opioid
      analgesics may reduce the development of tolerance and possibly attenuate the
      potential for opioid abuse.

PMID- 25048684
TI  - Quantity effect of radial cracks on the cracking propagation behavior and the
      crack morphology.
AB  - In this letter, the quantity effect of radial cracks on the cracking propagation
      behavior as well as the circular crack generation on the impacted glass plate
      within the sandwiched glass sheets are experimentally investigated via high-speed
      photography system. Results show that the radial crack velocity on the backing
      glass layer decreases with the crack number under the same impact conditions
      during large quantities of repeated experiments. Thus, the "energy conversion
      factor" is suggested to elucidate the physical relation between the cracking
      number and the crack propagation speed. Besides, the number of radial crack also
      takes the determinative effect in the crack morphology of the impacted glass
      plate. This study may shed lights on understanding the cracking and propagation
      mechanism in laminated glass structures and provide useful tool to explore the
      impact information on the cracking debris. 

PMID- 25048685
TI  - The size of the primary tumor and age at initial diagnosis are independent
      predictors of the metastatic behavior and survival of patients with SDHB-related
      pheochromocytoma and paraganglioma: a retrospective cohort study.
AB  - BACKGROUND: Succinate dehydrogenase subunit B (SDHB) mutations are associated
      with aggressive pheochromocytoma (PHEO)/paraganglioma (PGL) behavior, often
      resulting in metastatic disease and fatal outcomes. These tumors are often
      larger, extra-adrenal, and contain lower catecholamine concentrations than other
      hereditary PHEOs/PGLs. This study evaluated the size and age at diagnosis of
      primary SDHB-related PHEOs/PGLs as independent predictors of their metastatic
      behavior and outcome (survival). METHODS: One hundred six patients with SDHB
      mutation-related PHEO/PGL were included in this retrospective study. The recorded
      largest diameters, locations, and patient ages at initial diagnosis of SDHB
      related primary tumors were analyzed in the context of time to metastasis and
      patient survival. RESULTS: First, the development of metastatic disease in
      patients with primary tumors >=4.5 cm was significantly earlier than in patients
      with smaller tumors (P = 0.003). Second, patients with primary tumors larger than
      5.5 cm also had worse overall survival than patients with smaller tumors (P =
      0.008). Third, age at initial diagnosis was found to be an independent predictor
      of patient survival (PHEOs: P = 0.041; PGLs: P < 0.001). Fourth, we did not
      observe a significant difference in survival based on the specific SDHB mutations
      or patient sex. CONCLUSION: Receiver operating characteristic curves established
      4.5 cm as the best value to dichotomize the primary SDHB-related PHEO/PGL in
      order to evaluate the development of metastatic disease and 5.5 cm as the best
      value for survival prediction. Subsequently, the size of the primary tumor was
      found as an age-independent predictor of patient survival and metastases
      development in PGL. In both PHEO and PGL, age at diagnosis was found to be a size
      independent predictor of patient survival. No significant difference was found in
      metastases development or patient survival between males and females or among
      specific SDHB mutations. This data further extends and supports previous
      recommendations that carriers with SDHB mutations must undergo early and regular
      evaluations to detect PHEO/PGL in order to achieve the best clinical outcome.

PMID- 25048686
TI  - ZAP-70 genotype disrupts the relationship between microbiota and host, leading to
      spondyloarthritis and ileitis in SKG mice.
AB  - OBJECTIVE: The spondyloarthritides share genetic susceptibility, interleukin-23
      (IL-23) dependence, and the involvement of microbiota. The aim of the current
      study was to elucidate how host genetics influence gut microbiota and the
      relationship between microbiota and organ inflammation in spondyloarthritides.
      METHODS: BALB/c ZAP-70(W163C) -mutant (SKG) mice, Toll-like receptor 4 (TLR-4)
      deficient SKG mice, and wild-type BALB/c mice were housed under specific pathogen
      free conditions. SKG and wild-type BALB/c mice were maintained under germ-free
      conditions, and some of these mice were recolonized with altered Schaedler flora.
      All of the mice were injected intraperitoneally with microbial beta-1,3-glucan
      (curdlan). Arthritis, spondylitis, and ileitis were assessed histologically.
      Microbiome composition was analyzed in serial fecal samples obtained from mice
      that were co-housed beginning at the time of weaning, using 454 pyrosequencing.
      Infiltrating cells and cytokines in the peritoneal cavity were measured by flow
      cytometry and enzyme-linked immunosorbent assay. Cytokine, endoplasmic reticulum
      (ER) stress marker, and tight junction protein transcription was measured by
      quantitative real-time polymerase chain reaction. RESULTS: Microbiota content and
      response to curdlan varied according to whether T cell receptor signal strength
      was normal or was impaired due to the ZAP-70(W163C) mutation. Curdlan triggered
      acute inflammation regardless of the presence of the SKG allele or microbiota.
      However, no or limited microbiota content attenuated the severity of arthritis.
      In contrast, ileal IL-23 expression, ER stress, lymph node IL-17A production,
      goblet cell loss, and ileitis development were microbiota-dependent. Ileitis but
      not arthritis was suppressed by microbiota transfer upon co-housing SKG mice with
      wild-type BALB/c mice, as well as by TLR-4 deficiency. CONCLUSION: The
      interaction between immunogenetic background and host microbiota leads to an IL
      23-dependent loss of mucosal function, triggering ileitis in response to curdlan.

PMID- 25048688
TI  - Adjuvant therapy for renal cell carcinoma.
AB  - In the past few years, several targeted therapies have been approved by the U.S.
      Food and Drug Administration for the treatment of advanced renal cell carcinoma.
      This has led to an improvement in the progression-free survival and quality of
      life for these patients. Nevertheless, the use of these and other therapies in
      the adjuvant setting has failed to demonstrate a clear benefit. Immune therapies
      and hormonal or targeted therapies have been studied in this indication, and
      there are clinical trials currently enrolling patients with high risk of relapse.
      This article reviews the available data and the ongoing trials exploring the role
      of adjuvant therapy for kidney cancer. 

PMID- 25048687
TI  - Patient-reported outcome measures for systemic lupus erythematosus clinical
      trials: a review of content validity, face validity and psychometric performance.
AB  - BACKGROUND: Despite overall progress in treatment of autoimmune diseases,
      patients with systemic lupus erythematosus (SLE) experience many inflammatory
      symptoms representing an unmet medical need. This study aimed to create a
      conceptual model of the humanistic and economic burden of SLE, and review the
      patient-reported outcomes (PROs) used to measure such concepts in SLE clinical
      trials. METHODS: A conceptual model for SLE was developed from structured review
      of published articles from 2007 to August 2013 identified from literature
      databases (MEDLINE, EMBASE, PsycINFO, EconLit) plus other sources (PROLabels,
      FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptoms/impacts were
      identified from the literature. They were reviewed in the context of available
      guidance and assessed for face and content validity and psychometric properties
      to determine appropriateness for use in SLE trials. RESULTS: The conceptual model
      identified fatigue, pain, cognition, daily activities, emotional well-being,
      physical/social functioning and work productivity as key SLE concepts. Of the 68
      articles reviewed, 38 reported PRO data. From these and the other sources, 15
      PROs were selected for review, including SLE-specific health-related quality of
      life (HRQoL) measures (n = 5), work productivity (n = 1), and generic measures of
      fatigue (n = 3), pain (n = 2), depression (n = 2) and HRQoL (n = 2). The
      Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue),
      Brief Pain Inventory (BPI-SF) and LupusQoL demonstrated the strongest face
      validity, conceptual coverage and psychometric properties measuring key concepts
      in the conceptual model. All PROs reviewed, except for three Lupus-specific
      measures, lacked qualitative SLE patient involvement during development. The
      Hospital Anxiety and Depression Scale (HADS), Short Form [36 item] Health Survey
      version 2 (SF-36v2), EuroQoL 5-dimensions (EQ-5D-3L and EQ-5D-5L) and Work
      Productivity and Activity Impairment Questionnaire: Lupus (WPAI:Lupus) showed
      suitability for SLE economic models. CONCLUSIONS: Based on the identification of
      key symptoms and impacts of SLE using a scientifically sound conceptual model, we
      conclude that SLE is a condition associated with high unmet need and considerable
      burden to patients. This review highlights the availability and need for disease
      specific and generic patient-reported measures of relevant domains of disease
      signs and symptoms, HRQoL and work productivity, providing useful insight for SLE
      clinical trial design.

PMID- 25048689
TI  - Independence does not come with the method--treatment of neurogenic bowel
      dysfunction in children with myelomeningocele.
AB  - AIM: The aim was to evaluate and compare different bowel regimes with regard to
      satisfaction, faecal incontinence and independence, and the relationship to
      quality of life among children with myelomeningocele (MMC). METHODS: A
      questionnaire, including the health-related quality of life instrument PedsQL
      4.0TM, was sent to all children aged seven to 16 years (n = 172) with MMC,
      treated at two centres in Sweden and one in Norway. The three centres cover a
      third of the population in the two countries. The response rate was 62%. RESULTS:
      Parents of children (30%) using antegrade colonic enemas (ACE) reported higher
      satisfaction (p = 0.01) than the parents of those (47%) using transanal
      irrigation (TAI). The children reported no significant difference. Children and
      parents in the ACE group reported more complete evacuation of the bowels than the
      TAI group. No significant difference was found in faecal incontinence or
      independent toileting. The children (40%) who emptied their bowels independently
      reported a higher quality of life. Children using TAI or ACE spent around one
      hour on the toilet at every bowel emptying. CONCLUSION: TAI and ACE are effective
      treatments, but time-consuming and difficult to perform independently. Higher
      parental satisfaction is obtained with ACE. Irrespective of method the children
      who can use the toilet independently report a higher quality of life, which makes
      efforts to support independence valuable.

PMID- 25048690
TI  - Phytosterols and their extraction from various plant matrices using supercritical
      carbon dioxide: a review.
AB  - Phytosterols provide important health benefits: in particular, the lowering of
      cholesterol. From environmental and commercial points of view, the most
      appropriate technique has been searched for extracting phytosterols from plant
      matrices. As a green technology, supercritical fluid extraction (SFE) using
      carbon dioxide (CO2) is widely used to extract bioactive compounds from different
      plant matrices. Several studies have been performed to extract phytosterols using
      supercritical CO2 (SC-CO2) and this technology has clearly offered potential
      advantages over conventional extraction methods. However, the efficiency of SFE
      technology fully relies on the processing parameters, chemistry of interest
      compounds, nature of the plant matrices and expertise of handling. This review
      covers SFE technology with particular reference to phytosterol extraction using
      SC-CO2. Moreover, the chemistry of phytosterols, properties of supercritical
      fluids (SFs) and the applied experimental designs have been discussed for better
      understanding of phytosterol solubility in SC-CO2.

PMID- 25048692
TI  - Unprotected sexual practice and associated factors among People Living with HIV
      at Ante Retroviral Therapy clinics in Debrezeit Town, Ethiopia: a cross sectional
      study.
AB  - BACKGROUND: Magnitude of unprotected sexual practice among PLHIV is generally
      high in African countries including Ethiopia. Understanding the practice in
      Ethiopia could have public health significance. However little is known about the
      issue of unprotected sexual practice among PLHIV in Ethiopia. Hence, this study
      was aimed to assess unprotected sexual practice and associated factors among
      PLHIV at ART clinics in Debrezeit town. METHOD: Institution based cross-sectional
      study was conducted. A total of 667 PLHIV were included in the study. Systematic
      random sampling technique was used to select participants. Analyses were done
      using SPSS for windows version 15. A crude and adjusted odds ratio with 95%
      confidence interval was used to measure association between different factors and
      unprotected sex. RESULT: The prevalence of unprotected sexual practice among
      PLHIV was 22.2% [95% CI: (19.0-25.4)]. Factors associated with unprotected sexual
      practice include: being female (AOR=2.1, 95% CI (1.1, 3.9)), being
      divorced/widowed/separated (AOR=4.9, 95% CI (2.1, 11.6)), length of stay with the
      current partner for >= 49 months (AOR=3.3, 95% CI (1.9, 5.7)) and not discussing
      or partly discussing about safe sex and condom use with sexual partner (AOR=17.1,
      95% CI (8.9, 32.8)). CONCLUSION: High proportions of PLHIV were found to engage
      in unprotected sex. Information Education and Communication (IEC) on safe sex for
      PLHIV should target females, those who stayed longer with their partner and
      divorced/widowed/separate ones.

PMID- 25048693
TI  - Evaluation of the effect of expansion and shear stress on a self-assembled
      endothelium mimicking nanomatrix coating for drug eluting stents in vitro and in
      vivo.
AB  - Coating stability is increasingly recognized as a concern impacting the long-term
      effectiveness of drug eluting stents (DES). In particular, unstable coatings have
      been brought into focus by a recently published report (Denardo et al 2012 J. Am.
      Med. Assoc. 307 2148-50). Towards the goal of overcoming current challenges of
      DES performance, we have developed an endothelium mimicking nanomatrix coating
      composed of peptide amphiphiles that promote endothelialization, but limit smooth
      muscle cell proliferation and platelet adhesion. Here, we report a novel water
      evaporation based method to uniformly coat the endothelium mimicking nanomatrix
      onto stents using a rotational coating technique, thereby eliminating residual
      chemicals and organic solvents, and allowing easy application to even
      bioabsorbable stents. Furthermore, the stability of the endothelium mimicking
      nanomatrix was analyzed after force experienced during expansion and shear stress
      under simulated physiological conditions. Results demonstrate uniformity and
      structural integrity of the nanomatrix coating. Preliminary animal studies in a
      rabbit model showed no flaking or peeling, and limited neointimal formation or
      restenosis. Therefore, it has the potential to improve the clinical performance
      of DES by providing multifunctional endothelium mimicking characteristics with
      structural integrity on stent surfaces. 

PMID- 25048694
TI  - The comparability of men who have sex with men recruited from venue-time-space
      sampling and facebook: a cohort study.
AB  - BACKGROUND: Recruiting valid samples of men who have sex with men (MSM) is a key
      component of the US human immunodeficiency virus (HIV) surveillance and of
      research studies seeking to improve HIV prevention for MSM. Social media, such as
      Facebook, may present an opportunity to reach broad samples of MSM, but the
      extent to which those samples are comparable with men recruited from venue-based,
      time-space sampling (VBTS) is unknown. OBJECTIVE: The objective of this study was
      to assess the comparability of MSM recruited via VBTS and Facebook. METHODS: HIV
      negative and HIV-positive black and white MSM were recruited from June 2010 to
      December 2012 using VBTS and Facebook in Atlanta, GA. We compared the self
      reported venue attendance, demographic characteristics, sexual and risk
      behaviors, history of HIV-testing, and HIV and sexually transmitted infection
      (STI) prevalence between Facebook- and VTBS-recruited MSM overall and by race.
      Multivariate logistic and negative binomial models estimated age/race adjusted
      ratios. The Kaplan-Meier method was used to assess 24-month retention. RESULTS:
      We recruited 803 MSM, of whom 110 (34/110, 30.9% black MSM, 76/110, 69.1% white
      MSM) were recruited via Facebook and 693 (420/693, 60.6% black MSM, 273/693,
      39.4% white MSM) were recruited through VTBS. Facebook recruits had high rates of
      venue attendance in the previous month (26/34, 77% among black and 71/76, 93%
      among white MSM; between-race P=.01). MSM recruited on Facebook were generally
      older, with significant age differences among black MSM (P=.02), but not white
      MSM (P=.14). In adjusted multivariate models, VBTS-recruited MSM had fewer total
      partners (risk ratio [RR]=0.78, 95% CI 0.64-0.95; P=.01) and unprotected anal
      intercourse (UAI) partners (RR=0.54, 95% CI 0.40-0.72; P<.001) in the previous 12
      months. No significant differences were observed in HIV testing or HIV/STI
      prevalence. Retention to the 24-month visit varied from 81% for black and 70% for
      white MSM recruited via Facebook, to 77% for black and 78% for white MSM
      recruited at venues. There was no statistically significant differences in
      retention between the four groups (log-rank P=.64). CONCLUSIONS: VBTS and
      Facebook recruitment methods yielded similar samples of MSM in terms of HIV
      testing patterns, and prevalence of HIV/STI, with no differences in study
      retention. Most Facebook-recruited men also attended venues where VTBS
      recruitment was conducted. Surveillance and research studies may recruit via
      Facebook with little evidence of bias, relative to VBTS.

PMID- 25048695
TI  - Catalytic efficiency of designed catalytic proteins.
AB  - The de novo design of catalysts that mimic the affinity and specificity of
      natural enzymes remains one of the Holy Grails of chemistry. Despite decades of
      concerted effort we are still unable to design catalysts as efficient as enzymes.
      Here we critically evaluate approaches to (re)design of novel catalytic function
      in proteins using two test cases: Kemp elimination and ester hydrolysis. We show
      that the degree of success thus far has been modest when the rate enhancements
      seen for the designed proteins are compared with the rate enhancements by small
      molecule catalysts in solvents with properties similar to the active site.
      Nevertheless, there are reasons for optimism: the design methods are ever
      improving and the resulting catalyst can be efficiently improved using directed
      evolution.

PMID- 25048696
TI  - Effectiveness of mite-impermeable covers: a hypothesis-generating meta-analysis.
AB  - Asthma is a heterogeneous disease. The subject of mite allergen control has
      evolved into a debate dominated by a Cochrane review by Gotzsche and Johansen
      (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187). A not well
      discussed aspect of that study is the selection by those authors of a univariate
      meta-analysis including various interventions. This study extends the meta
      analysis by Gotzsche and Johansen and aims to generate hypotheses on the
      effectiveness of various bedding interventions, including the coverage of all
      bedding elements. Trials were selected based on environmental criteria. The
      interventions were classified according to the number of barriers used.
      Standardized mean differences yielded the mite load, three physiological outcomes
      and asthma symptom scores. The influence of covariates was examined with a mixed
      effect model using the metafor package for meta-analysis in R. Twelve trials
      included 1187 observations. The interventions included one barrier or product
      (six trials), two barriers or partial control (four trials) and three barriers or
      integral control (two trials). The exposure data showed considerable
      heterogeneity (I(2) = 93%). The risk of bias significantly (P = 0.04) influenced
      the final load, the square root of the interaction between the baseline load and
      the type of intervention as well (95% CI: -0.66 to -0.07 MUg/g; P = 0.02).
      Changes in load showed similar tendencies. Health outcomes showed moderate to
      considerable heterogeneity (physiological outcomes I(2) = 44-94%; symptom score
      I(2) = 93%). A meta-regression of bedding interventions indicates that integral
      control most significantly reduced mite load when the load was high at baseline.
      The number of trials was too small to allow an appropriate examination of health
      outcomes. Future studies are suggested to test the hypothesis that allergic
      patients benefit from integral control when the baseline mite load is high.

PMID- 25048697
TI  - Multiple phenotypic changes associated with large-scale horizontal gene transfer.
AB  - Horizontal gene transfer often leads to phenotypic changes within recipient
      organisms independent of any immediate evolutionary benefits. While secondary
      phenotypic effects of horizontal transfer (i.e., changes in growth rates) have
      been demonstrated and studied across a variety of systems using relatively small
      plasmids and phage, little is known about the magnitude or number of such costs
      after the transfer of larger regions. Here we describe numerous phenotypic
      changes that occur after a large-scale horizontal transfer event (~1 Mb
      megaplasmid) within Pseudomonas stutzeri including sensitization to various
      stresses as well as changes in bacterial behavior. These results highlight the
      power of horizontal transfer to shift pleiotropic relationships and cellular
      networks within bacterial genomes. They also provide an important context for how
      secondary effects of transfer can bias evolutionary trajectories and interactions
      between species. Lastly, these results and system provide a foundation to
      investigate evolutionary consequences in real time as newly acquired regions are
      ameliorated and integrated into new genomic contexts. 

PMID- 25048700
TI  - Determinants of pulmonary hypertension development in moderate or severe aortic
      stenosis.
AB  - Pulmonary hypertension (PHT) is not uncommon in patients with aortic stenosis
      (AS) and portends a dismal prognosis. We attempted to determine the prevalence of
      PHT and to identify contributors to its development in patients with moderate or
      severe AS. A total of 189 patients were enrolled. Patients were divided into two
      groups according to the presence or absence of PHT, with a pulmonary artery
      systolic pressure cutoff value of 40 mmHg. Left ventricular (LV) systolic
      function was assessed by global longitudinal (LV-GLS), circumferential (LV-GCS)
      and radial (LV-GRS) strains on top of LV ejection fraction (LV-EF). The ratio of
      mitral E to septal mitral annular e' velocity (E/e') was calculated to estimate
      LV filling pressure. Fifty patients (26.5 %) had concomitant PHT. Patients with
      PHT had a higher prevalence of diabetes, a lower LV-EF, a higher E/e', a larger
      left atrial volume index, a smaller indexed aortic valve (AV) area, and a more
      reduced LV-GLS (all p < 0.05). However, LV-GRS and LV-GCS were similar in
      patients with or without PHT. On multivariate logistic regression analysis, LV
      GLS and E/e' were independently associated with PHT, whereas LV-EF and indexed AV
      area were not. PHT complicating moderate or severe AS is commonly found and is
      independently associated with systolic and diastolic dysfunction assessed by
      Doppler and strain imaging, but not with LV-EF.

PMID- 25048699
TI  - Increased Notch signalling inhibits anoikis and stimulates proliferation of
      prostate luminal epithelial cells.
AB  - The prostate epithelial lineage hierarchy remains inadequately defined. Recent
      lineage-tracing studies have implied the existence of prostate luminal epithelial
      progenitors with extensive regenerative capacity. However, this capacity has not
      been demonstrated in prostate stem cell activity assays, probably owing to the
      strong susceptibility of luminal progenitors to anoikis. Here we show that
      constitutive expression of Notch1 intracellular domain impairs secretory function
      of mouse prostate luminal cells, suppresses anoikis of luminal epithelial cells
      by augmenting NF-kappaB activity independent of Hes1, stimulates luminal cell
      proliferation by potentiating PI3K-AKT signalling, and rescues the capacities of
      the putative prostate luminal progenitors for unipotent differentiation in vivo
      and short-term self-renewal in vitro. Epithelial cell autonomous AR signalling is
      dispensable for the Notch-mediated effects. As Notch activity is increased in
      prostate cancers, and anoikis resistance is a hallmark for metastatic cancer
      cells, this study suggests a pro-metastatic function of Notch signalling during
      prostate cancer progression. 

PMID- 25048701
TI  - Phosphoregulation of the dimerization and functions of end-binding protein 1.

PMID- 25048702
TI  - Lysosomal chymotrypsin induces mitochondrial fission in apoptotic cells by
      proteolytic activation of calcineurin.

PMID- 25048704
TI  - Verbascoside--a review of its occurrence, (bio)synthesis and pharmacological
      significance.
AB  - Phenylethanoid glycosides are naturally occurring water-soluble compounds with
      remarkable biological properties that are widely distributed in the plant
      kingdom. Verbascoside is a phenylethanoid glycoside that was first isolated from
      mullein but is also found in several other plant species. It has also been
      produced by in vitro plant culture systems, including genetically transformed
      roots (so-called 'hairy roots'). Verbascoside is hydrophilic in nature and
      possesses pharmacologically beneficial activities for human health, including
      antioxidant, anti-inflammatory and antineoplastic properties in addition to
      numerous wound-healing and neuroprotective properties. Recent advances with
      regard to the distribution, (bio)synthesis and bioproduction of verbascoside are
      summarised in this review. We also discuss its prominent pharmacological
      properties and outline future perspectives for its potential application. 

PMID- 25048705
TI  - Human milk contains novel glycans that are potential decoy receptors for neonatal
      rotaviruses.
AB  - Human milk contains a rich set of soluble, reducing glycans whose functions and
      bioactivities are not well understood. Because human milk glycans (HMGs) have
      been implicated as receptors for various pathogens, we explored the functional
      glycome of human milk using shotgun glycomics. The free glycans from pooled milk
      samples of donors with mixed Lewis and Secretor phenotypes were labeled with a
      fluorescent tag and separated via multidimensional HPLC to generate a tagged
      glycan library containing 247 HMG targets that were printed to generate the HMG
      shotgun glycan microarray (SGM). To investigate the potential role of HMGs as
      decoy receptors for rotavirus (RV), a leading cause of severe gastroenteritis in
      children, we interrogated the HMG SGM with recombinant forms of VP8* domains of
      the RV outer capsid spike protein VP4 from human neonatal strains N155(G10P[11])
      and RV3(G3P[6]) and a bovine strain, B223(G10P[11]). Glycans that were bound by
      RV attachment proteins were selected for detailed structural analyses using
      metadata-assisted glycan sequencing, which compiles data on each glycan based on
      its binding by antibodies and lectins before and after exo- and endo-glycosidase
      digestion of the SGM, coupled with independent MS(n) analyses. These
      complementary structural approaches resulted in the identification of 32 glycans
      based on RV VP8* binding, many of which are novel HMGs, whose detailed structural
      assignments by MS(n) are described in a companion report. Although sialic acid
      has been thought to be important as a surface receptor for RVs, our studies
      indicated that sialic acid is not required for binding of glycans to individual
      VP8* domains. Remarkably, each VP8* recognized specific glycan determinants
      within a unique subset of related glycan structures where specificity differences
      arise from subtle differences in glycan structures. 

PMID- 25048706
TI  - Structural characterization by multistage mass spectrometry (MSn) of human milk
      glycans recognized by human rotaviruses.
AB  - We have shown that recombinant forms of VP8* domains of the human rotavirus outer
      capsid spike protein VP4 from human neonatal strains (N155(G10P[11]) and
      RV3(G3P[6]) and a bovine strain (B223) recognize unique glycans within the
      repertoire of human milk glycans. The accompanying study by Yu et al.(2),
      describes a human milk glycan shotgun glycan microarray that led to the
      identification of 32 specific glycans in the human milk tagged glycan library
      that were recognized by these human rotaviruses. These microarray analyses also
      provided a variety of metadata about the recognized glycan structures compiled
      from anti-glycan antibody and lectin binding before and after specific
      glycosidase digestions, along with compositional information from mass analysis
      by matrix-assisted laser desorption ionization-mass spectrometry. To deduce
      glycan sequence and utilize information predicted by analyses of metadata from
      each glycan, 28 of the glycan targets were retrieved from the tagged glycan
      library for detailed sequencing using sequential disassembly of glycans by ion
      trap mass spectrometry. Our aim is to obtain a deeper structural understanding of
      these key glycans using an orthogonal approach for structural confirmation in a
      single ion trap mass spectrometer. This sequential ion disassembly strategy
      details the complexities of linkage and branching in multiple compositions,
      several of which contained isomeric mixtures including several novel structures.
      The application of this approach exploits both library matching with standard
      materials and de novo approaches. This combination together with the metadata
      generated from lectin and antibody-binding data before and after glycosidase
      digestions provide a heretofore-unavailable level of analytical detail to glycan
      structure analysis. The results of these studies showed that, among the 28 glycan
      targets analyzed, 27 unique structures were identified, and 23 of the human milk
      glycans recognized by human rotaviruses represent novel structures not previously
      described as glycans in human milk. The functional glycomics analysis of human
      milk glycans provides significant insight into the repertoire of glycans
      comprising the human milk metaglycome. 

PMID- 25048707
TI  - A systems level analysis reveals transcriptomic and proteomic complexity in
      Ixodes ricinus midgut and salivary glands during early attachment and feeding.
AB  - Although pathogens are usually transmitted within the first 24-48 h of attachment
      of the castor bean tick Ixodes ricinus, little is known about the tick's
      biological responses at these earliest phases of attachment. Tick midgut and
      salivary glands are the main tissues involved in tick blood feeding and pathogen
      transmission but the limited genomic information for I. ricinus delays the
      application of high-throughput methods to study their physiology. We took
      advantage of the latest advances in the fields of Next Generation RNA-Sequencing
      and Label-free Quantitative Proteomics to deliver an unprecedented, quantitative
      description of the gene expression dynamics in the midgut and salivary glands of
      this disease vector upon attachment to the vertebrate host. A total of 373 of
      1510 identified proteins had higher expression in the salivary glands, but only
      110 had correspondingly high transcript levels in the same tissue. Furthermore,
      there was midgut-specific expression of 217 genes at both the transcriptome and
      proteome level. Tissue-dependent transcript, but not protein, accumulation was
      revealed for 552 of 885 genes. Moreover, we discovered the enrichment of tick
      salivary glands in proteins involved in gene transcription and translation, which
      agrees with the secretory role of this tissue; this finding also agrees with our
      finding of lower tick t-RNA representation in the salivary glands when compared
      with the midgut. The midgut, in turn, is enriched in metabolic components and
      proteins that support its mechanical integrity in order to accommodate and
      metabolize the ingested blood. Beyond understanding the physiological events that
      support hematophagy by arthropod ectoparasites, we discovered more than 1500
      proteins located at the interface between ticks, the vertebrate host, and the
      tick-borne pathogens. Thus, our work significantly improves the knowledge of the
      genetics underlying the transmission lifecycle of this tick species, which is an
      essential step for developing alternative methods to better control tick-borne
      diseases. 

PMID- 25048708
TI  - Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in
      human dermal fibroblasts.
AB  - BACKGROUND: Cathepsin K (CatK), a cysteine protease with the potent elastolytic
      activity, plays a predominant role in intracellular elastin degradation in human
      dermal fibroblasts (HDFs), and contributes to solar elastosis. In previous
      studies, CatK expression was downregulated in photoaged skin and fibroblasts, but
      upregulated in acute UVA-irradiated skin and fibroblasts. The underlying
      mechanisms regulating UVA-induced CatK expression remain elusive. OBJECTIVE: This
      study investigates mechanisms involved in the regulation of UVA-induced CatK
      expression in HDFs. METHODS: Primary HDFs were exposed to UVA. Cell proliferation
      was analyzed using a colorimetric assay of relative cell number. Quantitative
      real-time RT-PCR and Western blot were performed to detect CatK expression in
      HDFs on three consecutive days after 10 J/cm2 UVA irradiation, or cells treated
      with increasing UVA doses. UVA-activated MAPK/AP-1 pathway was examined by
      Western blot. Effects of inhibition of MAPK pathway and knockdown of Jun and Fos
      on UVA-induced CatK expression were also measured by real-time RT-PCR and Western
      blot. RESULTS: UVA significantly increased CatK mRNA and protein expression in a
      dose-dependent manner. UVA-induced CatK expression occurred along with UVA
      activated phosphorylation of JNK, p38 and Jun, UVA-increased expression of Fos.
      Inactivation of JNK and p38MAPK pathways both remarkably decreased UVA-induced
      CatK expression, which was suppressed more by inhibition of JNK pathway.
      Furthermore, knockdown of Jun and Fos significantly attenuated basal and UVA
      induced CatK expression. CONCLUSION: UVA is capable of increasing CatK expression
      in HDFs, most likely by activation of MAPK pathway and of AP-1, which has been
      shown to be the case for matrix metalloproteinases. As current strategies for
      selecting anti-photoaging agents focus on their ability to decrease MMPs'
      expression through inhibiting UV- activated MAPK pathway, future strategies
      should also consider their effect on CatK expression.

PMID- 25048709
TI  - A magnetic nanoparticle-based multiple-gene delivery system for transfection of
      porcine kidney cells.
AB  - Superparamagnetic nanoparticles are promising candidates for gene delivery into
      mammalian somatic cells and may be useful for reproductive cloning using the
      somatic cell nuclear transfer technique. However, limited investigations of their
      potential applications in animal genetics and breeding, particularly multiple
      gene delivery by magnetofection, have been performed. Here, we developed a
      stable, targetable and convenient system for delivering multiple genes into the
      nuclei of porcine somatic cells using magnetic Fe3O4 nanoparticles as gene
      carriers. After surface modification by polyethylenimine, the spherical magnetic
      Fe3O4 nanoparticles showed strong binding affinity for DNA plasmids expressing
      the genes encoding a green (DNAGFP) or red (DNADsRed) fluorescent protein. At
      weight ratios of DNAGFP or DNADsRed to magnetic nanoparticles lower than or equal
      to 10?1 or 5?1, respectively, the DNA molecules were completely bound by the
      magnetic nanoparticles. Atomic force microscopy analyses confirmed binding of the
      spherical magnetic nanoparticles to stretched DNA strands up to several hundred
      nanometers in length. As a result, stable and efficient co-expression of GFP and
      DsRed in porcine kidney PK-15 cells was achieved by magnetofection. The results
      presented here demonstrate the potential application of magnetic nanoparticles as
      an attractive delivery system for animal genetics and breeding studies. 

PMID- 25048710
TI  - Involvement of moesin in the development of morphine analgesic tolerance through
      P-glycoprotein at the blood-brain barrier.
AB  - Altered expression of P-glycoprotein (P-gp), a drug efflux transporter expressed
      by brain capillary endothelial cells (BCECs), may contribute to the development
      of opioid analgesic tolerance, as demonstrated by cumulative evidence from
      research. However, the detailed mechanism by which chronic morphine treatment
      increases P-gp expression remains unexplained. Ezrin/radixin/moesin (ERM) are
      scaffold proteins that are known to regulate the plasma membrane localization of
      some drug transporters such as P-gp in peripheral tissues, although a few reports
      suggest its role in the central nervous system as well. In this study, we
      investigated the involvement of ERM in the development of morphine analgesic
      tolerance through altered P-gp expression in BCECs. Repeated treatment with
      morphine (10 mg/kg/day, s.c. for 5 days) decreased its analgesic effect in the
      tail-flick test and increased P-gp protein expression in BCECs, as determined by
      Western blotting. Furthermore, moesin protein expression increased in the same
      fraction whereas that of ezrin decreased; no change was observed in the radixin
      expression. Furthermore, immunoprecipitation and immunofluorescence assays
      revealed interaction between moesin and P-gp molecules, along with co
      localization, in BCECs. In conclusion, an increase in moesin expression may
      contribute to the increased expression of P-gp in BCECs, leading to the
      development of morphine analgesic tolerance. 

PMID- 25048711
TI  - Development of high throughput screening assays and pilot screen for inhibitors
      of metalloproteases meprin alpha and beta.
AB  - Zinc metalloproteinases meprin alpha and meprin beta are implicated in a variety
      of diseases, such as fibrosis, inflammation and neurodegeneration, however, there
      are no selective small molecule inhibitors that would allow to study their role
      in these processes. To address this lack of molecular tools, we have developed
      high throughput screening assays to enable discovery of inhibitors of both meprin
      alpha and meprin beta and screened a collection of well characterized
      pharmaceutical agents (library of pharmaceutically active compounds, n = 1,280
      compounds). Two compounds (PPNDS, NF449) confirmed their activity and selectivity
      for meprin beta. Kinetic studies revealed competitive (PPNDS) and mixed
      competitive/noncompetitive (NF449) inhibition mechanisms suggesting that binding
      occurs in meprin beta active site. Both PPNDS and NF449 exhibited low nanomolar
      IC50 and Ki values making them the most potent and selective inhibitors of meprin
      beta reported to the date. These results demonstrate the ability of meprin alpha
      and beta assays to identify selective compounds and discard artifacts of primary
      screening.

PMID- 25048712
TI  - Synthesis and evaluation of antidepressant-like activity of some 4-substituted 1
      (2-methoxyphenyl)piperazine derivatives.
AB  - A series of new derivatives of N-(2-methoxyphenyl)piperazine have been
      synthesized for their affinity toward serotonergic receptors and for their
      potential antidepressant-like activity. They have been evaluated toward receptors
      5-HT1A , 5-HT6 , and 5-HT7 , as well as in vivo in the tail suspension, locomotor
      activity, and motor co-ordination tests. All the tested compounds proved very
      good affinities toward 5-HT1A and 5-HT7 receptors. The most promising compound
      was 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine
      hydrochloride, exhibiting affinity toward receptors Ki <1 nm (5-HT1A ) and Ki =
      34 nm (5-HT7 ). Antidepressant-like activity (tail suspension test) was observed
      at 2.5 mg/kg b.w. (mice, i.p.), and the effect was stronger than that observed
      for imipramine (5 mg/kg b.w.). Sedative activity was observed at ED50 (locomotor
      test, mice, i.p.) = 17.5 mg/kg b.w. and neurotoxicity was observed at TD50
      (rotarod, mice, i.p.) = 53.2 mg/kg b.w.

PMID- 25048713
TI  - The relationship between acute changes in the systemic inflammatory response and
      plasma ascorbic acid, alpha-tocopherol and lipid peroxidation after elective hip
      arthroplasty.
AB  - BACKGROUND & AIMS: Vitamin C (ascorbic acid, AA) is a water soluble vitamin with
      many functions including antioxidative properties, haemostasis, hormone
      synthesis, collagen synthesis, carnitine synthesis, bile salt production and
      enhancing iron absorption. There is some evidence that there is a negative
      inverse relationship between plasma vitamin C concentration and the systemic
      inflammatory response as measured by C-reactive protein (CRP). The aim of the
      present study was to examine, in the context of a longitudinal study, the change
      in plasma concentrations of ascorbic acid (AA) and Vitamin E (alpha-tocopherol,
      AT) and their relationship to free radical damage during the evolution of the
      systemic inflammatory response. METHODS: Venous blood samples were obtained pre
      operatively and at 1, 2, 3 and 90 days post-operatively from 11 patients
      undergoing elective hip arthroplasty at Glasgow Royal Infirmary. AA, AT,
      cholesterol, MDA (marker of free radical damage), CRP and albumin were measured
      in plasma. RESULTS: Plasma AA fell significantly by 74% (P < 0.01), AT fell by
      36% (P < 0.01), cholesterol by 40% (P < 0.01), MDA by 38% (P < 0.01), albumin by
      29% (P < 0.01) and CRP increased significantly by 160 fold (P < 0.01) during the
      systemic inflammatory response. The fall in plasma AA remained significant when
      adjusted for albumin (P < 0.01). Plasma AT adjusted for cholesterol did not
      change significantly during the study period. The fall in plasma MDA remained
      significant when adjusted for albumin (P 0.01). At 3 months post-operatively, all
      measurements (including AA) except albumin had returned to baseline values.
      CONCLUSIONS: Plasma AA levels are unlikely to be a reliable measurement of
      Vitamin C where there is evidence of a systemic inflammatory response. The
      decrease in plasma AA concentration is likely to be secondary to increased
      consumption, increased usage neutralising free radicals, increased utilisation in
      supporting AT regeneration and increased urinary excretion.

PMID- 25048714
TI  - Particle size determines effects of lipoprotein lipase on the catabolism of n-3
      triglyceride-rich particles.
AB  - BACKGROUND & AIMS: The catabolic pathways of n-3 triglyceride (TG) rich particles
      (n-3 TGRP) have not been clearly elucidated. In this study, we investigated the
      effects of lipoprotein lipase (LPL) on the catabolism of n-3 TGRP compared to n-6
      TGRP in vivo and in vitro, and we determined whether particle size affects the
      biological functions of LPL in n-3 TGRP catabolism. METHODS: Four types of lipid
      emulsions, chylomicron (CM)-sized n-3 TG and n-6 TG emulsions, and very low
      density lipoprotein (VLDL)-sized n-3 TG and n-6 TG emulsions, were labeled with
      1,1'-dioctadecy1-3,3,3',3'-tetramethylindo-carbocyanine perchlorate (DiI) and
      administered via a bolus injection to LPL gene knockout (LPL+/-) mice in vivo and
      were added to cultured LPL miRNA-transfected 3T3-L1 adipocytes in vitro. RESULTS:
      With CM-sized emulsions, a reduction in LPL expression in LPL+/- mice had almost
      no effect on tissue uptake of n-3 TG emulsions with smaller changes in their
      initial blood clearance; however, greater effects were observed for VLDL-sized n
      3 TG emulsions with respect to tissue uptake with greater changes in their
      initial blood clearance, compared to n-6 TG emulsions with the same size. In
      vitro, LPL miRNA transfection had smaller effects on CM-sized and greater effects
      on VLDL-sized n-3 TG emulsions, with respect to particle uptake, cell TG mass,
      particle-cell binding and particle lipolysis. CONCLUSION: These results suggested
      that LPL is more important for catabolism of n-3 TGRP of smaller size; whereas it
      is essential for catabolism of all sizes of n-6 TGRP.

PMID- 25048715
TI  - Honeybee colony disorder in crop areas: the role of pesticides and viruses.
AB  - As in many other locations in the world, honeybee colony losses and disorders
      have increased in Belgium. Some of the symptoms observed rest unspecific and
      their causes remain unknown. The present study aims to determine the role of both
      pesticide exposure and virus load on the appraisal of unexplained honeybee colony
      disorders in field conditions. From July 2011 to May 2012, 330 colonies were
      monitored. Honeybees, wax, beebread and honey samples were collected. Morbidity
      and mortality information provided by beekeepers, colony clinical visits and
      availability of analytical matrix were used to form 2 groups: healthy colonies
      and colonies with disorders (n = 29, n = 25, respectively). Disorders included:
      (1) dead colonies or colonies in which part of the colony appeared dead, or had
      disappeared; (2) weak colonies; (3) queen loss; (4) problems linked to brood and
      not related to any known disease. Five common viruses and 99 pesticides (41
      fungicides, 39 insecticides and synergist, 14 herbicides, 5 acaricides and
      metabolites) were quantified in the samples.The main symptoms observed in the
      group with disorders are linked to brood and queens. The viruses most frequently
      found are Black Queen Cell Virus, Sac Brood Virus, Deformed Wing Virus. No
      significant difference in virus load was observed between the two groups. Three
      acaricides, 5 insecticides and 13 fungicides were detected in the analysed
      samples. A significant correlation was found between the presence of fungicide
      residues and honeybee colony disorders. A significant positive link could also be
      established between the observation of disorder and the abundance of crop surface
      around the beehive. According to our results, the role of fungicides as a
      potential stressor for honeybee colonies should be further studied, either by
      their direct and/or indirect impacts on bees and bee colonies. 

PMID- 25048717
TI  - Regioselective conversion of arenes to N-aryl-1,2,3-triazoles using C-H
      borylation.
AB  - A one-pot protocol for the synthesis of N-aryl 1,2,3-triazoles from arenes by an
      iridium-catalyzed C?H borylation/copper catalyzed azidation/click sequence is
      described. 1 mol % of Cu(OTf)2 was found to efficiently catalyze both the
      azidation and the click reaction. The applicability of this method is
      demonstrated by the late-stage chemoselective installation of 1,2,3-triazole
      moiety into unactivated molecules of pharmaceutical importance. 

PMID- 25048718
TI  - Chemically tailoring coal to fluorescent carbon dots with tuned size and their
      capacity for Cu(II) detection.
AB  - The desired control of size, structure, and optical properties of fluorescent
      carbon dots (CDs) is critical for understanding the fluorescence mechanism and
      exploring their potential application. Herein, a top-down strategy to chemically
      tailor the inexpensive coal to fluorescent CDs by a combined method of
      carbonization and acidic oxidation etching is reported. The size and optical
      properties of the as-made CDs are tuned by controlling the structures of
      graphitic crystallites in the starting precursor. The coal-derived CDs exhibit
      two different distinctive emission modes, where the intensity of the short
      wavelength emission is significantly enhanced by partial reduction treatment. The
      evolution of the electronic structure and the surface states analysis show that
      two different types of fluorescence centers, nano-sized sp(2) carbon domains and
      surface defects, are responsible for the observed emission characteristics. The
      reduced CDs are demonstrated as an effective fluorescent sensing material for
      label-free and selective detection of Cu(II) ions with a detection limit as low
      as 2.0 nM, showing a great promise for real-world sensor applications.

PMID- 25048716
TI  - Immunological aspects of antiviral therapy of chronic hepatitis B virus and
      hepatitis C virus infections.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause a large proportion of
      acute and chronic liver disease worldwide. Over the past decades many
      immunological studies defined host immune responses that mediate spontaneous
      clearance of acute HBV and HCV infection. However, host immune responses are also
      relevant in the context of treatment-induced clearance of chronic HBV and HCV
      infection. First, the pretreatment level of interferon-stimulated genes as well
      as genetic determinants of innate immune responses, such as single nucleotide
      polymorphisms near the IFNL3 gene, are strong predictors of the response to
      interferon-alpha (IFN-alpha)-based therapy. Second, IFN-alpha, which has been a
      mainstay of HBV and HCV therapy over decades, and ribavirin, which has also been
      included in interferon-free direct antiviral therapy for HCV, modulate host
      immune responses. Third, both IFN-alpha-based and IFN-alpha-free treatment
      regimens of HBV and HCV infection alter the short-term and long-term adaptive
      immune response against these viruses. Finally, treatment studies have not just
      improved the clinical outcomes, but also provided opportunities to study virus
      host interaction. This review summarizes our current knowledge on how a patient's
      immune response affects the treatment outcome of HBV and HCV infection and how
      innate and adaptive immune responses themselves are altered by the different
      treatment regimens.

PMID- 25048719
TI  - Treating chronic non-cancer pain in older people--more questions than answers?
AB  - There is little evidence specifically relating to drug treatments for pain in
      older people, but much can be extrapolated from what we already know. The
      evidence about drug treatments for chronic non-cancer pain is changing, driven by
      major improvements in understanding of clinical trial analysis and by the
      adoption of patient-centered outcomes of proven economic benefit. There is clear
      evidence of lack of useful effect, or insufficient evidence of effect for a
      number of commonly used drugs, including paracetamol, topical rubefacients, low
      concentration topical capsaicin, and for strong opioids in chronic non-cancer
      pain. In musculoskeletal pain there is evidence of efficacy for NSAIDs, tramadol,
      and tapentadol, and in neuropathic pain for duloxetine, pregabalin, and
      gabapentin, with weak evidence for amitriptyline. The new perspective is of drugs
      that work well in a minority of patients, but hardly at all in the remainder. The
      goal of treatment is large reductions in pain, by 50% or more. This outcome, and
      only this outcome, is associated with large benefits in terms of improved sleep,
      reduced depression, and large gains in function and quality of life. It is not
      possible to predict which patient will benefit from which drug, but early success
      or failure appears to be predictive of long-term success or failure. The emphasis
      is on stopping treatments that do not work and switching to other drugs in the
      same or different class, so that any potential future risk of treatment is
      balanced by very large and immediate benefit. 

PMID- 25048720
TI  - Measurement of intracellular pH changes based on DNA-templated capsid protein
      nanotubes.
AB  - Intracellular pH (pHi) is a fundamental modulator of cell function. Minute
      changes in pHi may cause great effects in many cellular activities such as
      metabolism and signal transduction. Herein we report an electrochemical pHi
      sensor based on viral-coat proteins-DNA nanotubes modified gold electrode. The
      sensor is pH-sensitive as a result of the pH-dependent electrochemical property
      of methylene blue (MB) and cell permeable owing to the polyarginine domain of the
      cowpea chlorotic mottle virus (CCMV) coat protein. Moreover, because the pH
      sensor can be translocated into cells without any further operations, the
      measurement of pHi changes can be greatly simplified. The pH sensor has a broad
      pH spectrum in the pH range from 4.0 to 9.0 and responds rapidly to the pH
      changes of cells, so it may hold great potential to be a valuable tool to study
      pH-dependent biological and pathological processes in the future. 

PMID- 25048721
TI  - Does life satisfaction predict five-year mortality in community-living older
      adults?
AB  - OBJECTIVES: Depression and depressive symptoms predict death, but it is less
      clear if more general measures of life satisfaction (LS) predict death. Our
      objectives were to determine: (1) if LS predicts mortality over a five-year
      period in community-living older adults; and (2) which aspects of LS predict
      death. METHOD: 1751 adults over the age of 65 who were living in the community
      were sampled from a representative population sampling frame in 1991/1992 and
      followed five years later. Age, gender, and education were self-reported. An
      index of multimorbidity and the Older American Resource Survey measured health
      and functional status, and the Terrible-Delightful Scale assessed overall LS as
      well as satisfaction with: health, finances, family, friends, housing,
      recreation, self-esteem, religion, and transportation. Cox proportional hazards
      models examined the influence of LS on time to death. RESULTS: 417 participants
      died during the five-year study period. Overall LS and all aspects of LS except
      finances, religion, and self-esteem predicted death in unadjusted analyses. In
      fully adjusted analyses, LS with health, housing, and recreation predicted death.
      Other aspects of LS did not predict death after accounting for functional status
      and multimorbidity. CONCLUSION: LS predicted death, but certain aspects of LS are
      more strongly associated with death. The effect of LS is complex and may be
      mediated or confounded by health and functional status. It is important to
      consider different domains of LS when considering the impact of this important
      emotional indicator on mortality among older adults.

PMID- 25048722
TI  - CYR61 overexpression associated with the development and poor prognosis of
      ovarian carcinoma.
AB  - Cysteine-rich 61 (CYR61) has been proven to be an oncogene with potential
      predictive and prognostic implications in a variety of human cancers. However,
      the expression pattern of CYR61 and its role in ovarian carcinoma remains largely
      unknown. In this study, the mRNA and protein levels of CYR61 in normal ovaries
      and ovarian carcinoma tissues were evaluated using reverse transcription
      polymerase chain reaction, immunohistochemistry, and Western blotting. Compared
      to normal ovarian tissues, the mRNA and protein levels of CYR61 were
      significantly higher in ovarian carcinoma tissues. Moreover, receiver operating
      characteristic (ROC) curve analysis, Spearman's rank correlation, Kaplan-Meier
      plots, and the Cox proportional hazards regression model were used to investigate
      the potential association of the CYR61 protein with the development of ovarian
      carcinoma in an ovarian carcinoma cohort. Based on ROC curve analysis, high
      expression of CYR61 was defined as a tumor in which more than 70 % of cells were
      positively stained. Based on this cutoff value, high expression of CYR61 was
      detected in 51.5 % of invasive carcinomas, 35.3 % of borderline tumors, 25.9 % of
      cystadenomas, and 20 % in the normal ovaries. In ovarian carcinomas, CYR61
      overexpression was associated with advanced FIGO stage. Univariate survival
      analysis on the ovarian carcinoma cohorts showed that overexpression of CYR61 was
      associated with poor survival of ovarian cancer patients. Multivariate analysis
      suggested that the protein level of CYR61 was an independent and significant
      prognostic factor for ovarian carcinoma. Our results suggest that the CYR61
      protein is an important and independent biomarker for prognostic implications of
      ovarian carcinoma.

PMID- 25048724
TI  - Biomarkers in prostate cancer: new era and prospective.
AB  - Currently, most men are diagnosed with prostate cancer (PCa) after a prostate
      specific antigen (PSA) test shows an elevated level of the PSA protein. An
      elevated level suggests cancer may be present. If an elevation is detected, a
      biopsy to detect cancer is followed. But the PSA test is controversial. An
      elevated level does not always mean there is cancer present. The test often leads
      men to having unnecessary biopsies and treatments. Even if cancer is found on
      biopsy, many of these cancers are slow growing and would not impact the lives of
      the men who have them. Current advances in molecular techniques have provided new
      tools facilitating the discovery of new biomarkers for PCa. The purpose of this
      review is to examine the advances in PCa biomarkers and implication for possible
      improving disease outcome. The future of cancer prognosis may rely on small
      panels of markers that can accurately predict PCa presence, stage, and metastasis
      and can serve as prognosticators, targets, and/or surrogate endpoints of disease
      progression and response to therapy. 

PMID- 25048723
TI  - Inching toward cure of acute myeloid leukemia: a summary of the progress made in
      the last 50 years.
AB  - Despite some claims to the contrary, I believe substantial progress has been made
      in the last half century toward cure of acute myeloid leukemia in children and
      adults. The tried and true mechanism for this progress has been clinical trial
      and error. This method has been supplemented with an ever-increasing amount of
      work at the clinical laboratory interface that is beginning to allow us to
      develop specific therapy for afflicted individuals. This review details where we
      stand today and how we got here. 

PMID- 25048726
TI  - Integrating curricula on human trafficking into medical education and residency
      training.

PMID- 25048725
TI  - Elevated expression of CRYAB predicts unfavorable prognosis in non-small cell
      lung cancer.
AB  - Alpha B-crystallin (CRYAB) is one of the principal members of the small heat
      shock protein family, and several studies described the CRYAB expression in human
      cancers. However, the association between CRYAB expression and the clinical
      features of non-small cell lung cancer (NSCLC) is rarely elucidated. In this
      present study, one-step quantitative reverse transcription-polymerase chain
      reaction with 12 fresh-frozen NSCLC samples and Western blotting as well as
      immunohistochemistry (IHC) analyses in 101 NSCLC cases were conducted to
      investigate the relationship between CRYAB expression and the clinicopathological
      attributes of NSCLC. The results showed that CRYAB mRNA and protein expression
      levels were significantly higher in NSCLC than in matched non-cancerous tissues
      (p < 0.05). The IHC data indicated that the CRYAB protein expression in NSCLC was
      significantly correlated with TNM stage (p = 0.043), and overall survival (p =
      0.029). Kaplan-Meier method and Cox multifactor analysis suggested that higher
      CRYAB protein level (p = 0.032) and TNM stage (p = 0.048) were statistically
      associated with the poor survival of patients with NSCLC. The data suggested that
      CRYAB may be identified as a novel prognostic marker and targeting CRYAB may
      provide a promising strategy for NSCLC treatment.

PMID- 25048727
TI  - Single-incision laparoscopic appendectomy for treating appendicitis in a patient
      with gastrointestinal malrotation.
AB  - INTRODUCTION: Intestinal malrotation is a rare congenital anomaly, and acute
      appendicitis associated with intestinal malrotation is extremely rare.
      PRESENTATION OF CASE We report a rare case of a 47-year-old Japanese woman
      diagnosed with barium-related perforated appendicitis associated with intestinal
      malrotation. We used a transumbilical single-incision laparoscopic approach to
      resect the appendix, and the procedure was completed successfully without
      perioperative complications. DISCUSSION: To our knowledge, single-incision
      laparoscopic surgery for appendicitis associated with intestinal malrotation has
      not been reported yet. In cases with mobile cecum such as this one, mobilization
      from inflammatory adhesion of the surrounding structures is easy. CONCLUSION: We
      conclude that transumbilical single-incision laparoscopic appendectomy is a
      simple and less invasive method for treating appendicitis associated with
      intestinal malrotation.

PMID- 25048728
TI  - Lateralization of olfactory processing: differential impact of right and left
      temporal lobe epilepsies.
AB  - Olfactory processes were reported to be lateralized. The purpose of this study
      was to further explore this phenomenon and investigate the effect of the
      hemispheric localization of epileptogenic foci on olfactory deficits in patients
      with temporal lobe epilepsy (TLE). Olfactory functioning was assessed in 61
      patients and 60 healthy control (HC) subjects. The patients and HC subjects were
      asked to rate the intensity, pleasantness, familiarity, and edibility of 12
      common odorants and then identify them. Stimulations were delivered monorhinally
      in the nostril ipsilateral to the epileptogenic focus in TLE and arbitrarily in
      either the left or the right nostril in the HC subjects. The results demonstrated
      that regardless of the side of stimulation, patients with TLE had reduced
      performance in all olfactory tasks compared with the HC subjects. With regard to
      the side of the epileptogenic focus, patients with left TLE judged odors as less
      pleasant and had more difficulty with identification than patients with right
      TLE, underlining a privileged role of the left hemisphere in the emotional and
      semantic processing of odors. Finally, irrespective of group, a tendency towards
      a right-nostril advantage for judging odor familiarity was found in agreement
      with a prominent role of the right hemisphere in odor memory processing. 

PMID- 25048729
TI  - Trace element contamination in the Guadalquivir River Estuary ten years after the
      Aznalcollar mine spill.
AB  - Sediments, clams Scrobicularia plana and worms Hediste diversicolor from the
      Guadalquivir estuary were collected ten years after the Aznalcollar mine spill
      and analyzed for metals. Significant seasonal and spatial effects were detected
      for most elements, so data from different sampling periods and locations were
      treated separately. Overall, the most polluted sites were found upstream,
      although Zn and Cu tended to accumulate at the estuary mouth. A significant
      decline of Zn in sediments and clams was observed compared to levels reported
      following the spill, so the estuarine ecosystem has recovered. However, the
      concentrations of some elements in S. plana were still higher than those of
      heavily contaminated regions. In this mollusk, Pb and As levels were higher in
      2008 than in previous years, suggesting a new source entering into the estuary.
      Metals in sediments presented low bioavailability for biota, so other sources
      must account for the concentrations observed in these species. 

PMID- 25048730
TI  - Temporal changes in TBT pollution in water, sediment, and oyster from Jinhae Bay
      after the total ban in South Korea.
AB  - Temporal change in tributyltin (TBT) levels in Jinhae Bay, which has various TBT
      sources, was investigated in water, sediments, and oysters from 2003 to 2013
      after its total ban in South Korea. The seawater TBT levels decreased over 500
      fold from 1995/97 to 2008/09. The oyster TBT levels were about fourfold lower in
      2012/13 than in 1995/97. However, the sediment TBT levels did not significantly
      change, even 10 years after the partial TBT ban on small ships and 7 years after
      the total TBT ban on all oceangoing vessels in Korea. The total ban of TBT use
      effectively reduced water and oyster TBT levels in Jinhae Bay, but TBT levels in
      water, oysters, and sediment remained above the global environmental quality
      standards established to protect marine organisms.

PMID- 25048731
TI  - A qualitative study to develop a patient-reported outcome for dysmenorrhea.
AB  - PURPOSE: Dysmenorrhea refers to the experience of pelvic pain/cramps experienced
      by women around or during menstruation. A literature review indicated that no
      existing patient-reported outcome measure was adequate to support labeling claims
      in dysmenorrhea. Therefore, this study aimed to develop a new measure that could
      be used as a primary end point in dysmenorrhea clinical trials. METHODS: Open
      ended interviews were conducted with 52 dysmenorrhea patients, including a subset
      of 12 women with a comorbid pelvic pain condition (PPC). Verbatim transcripts
      were analyzed thematically. The findings were used to generate draft items for an
      electronic diary (eDiary). A further 24 dysmenorrhea patients pilot-tested the
      eDiary for 1-5 weeks and completed cognitive interviews to assess content
      validity. Revisions to the eDiary were implemented based on the findings.
      RESULTS: In the first set of interviews, 51 women (98 %) spontaneously reported
      pain/cramps in or around the pelvic region (abdomen, lower back, legs/upper
      thighs, and vaginal area). Pain experiences reported were similar across
      dysmenorrhea and dysmenorrhea plus PPC subgroups, except that the pelvic pain
      among PPC patients occurred throughout the month, not only during menstruation.
      All participants described the detrimental impact of dysmenorrhea on health
      related quality of life. CONCLUSIONS: The eDiary was conceptually comprehensive
      and easy to complete/understand during cognitive debriefing. The resulting nine
      item diary included assessment of: menstrual bleeding severity; pain severity;
      use of analgesics; impact on work/school, physical activities, social and leisure
      activities, and sleep. Psychometric validation is ongoing and will assess the
      reliability, validity, and responsiveness of the eDiary as a comprehensive
      dysmenorrhea assessment.

PMID- 25048732
TI  - Pulmonary radiographic findings in young children with cystic fibrosis.
AB  - BACKGROUND: Pulmonary evaluation is one of the greatest challenges in children
      with cystic fibrosis who are younger than 6 years. Although chest CT can provide
      the most information for initial and progressive changes in cystic fibrosis, the
      radiation exposures can lead to significant cumulative exposure in children as
      they are followed with serial scanning to monitor early and progressive disease.
      Therefore the systematized study of chest radiographs using the Brasfield score
      has been used scientifically with the aim of evaluating the evolution of
      pulmonary abnormalities in children with cystic fibrosis. OBJECTIVE: This study
      was performed to assess the radiologic findings in children younger than 6 years
      with cystic fibrosis. We used the Brasfield score to compare radiographs
      performed in patients with Pseudomonas aeruginosa vs. oxacillin-sensitive
      Staphylococcus aureus and to compare radiographs in children with early vs.
      delayed diagnosis. MATERIALS AND METHODS: A total of 254 chest radiographs from
      67 children who had undergone material cultures of the airways as part of routine
      care were evaluated in this cross-sectional study. The statistical analysis was
      performed by the Kruskal-Wallis test, with a significance level of 5%. RESULTS:
      Approximately 35.8% of chest radiographs had a Brasfield score lower than 21
      points, which is compatible with potentially irreversible pulmonary disease.
      Brasfield scores decreased (this score decreases with increasing disease
      severity) in older children, and both bacterial colonization with Pseudomonas and
      later diagnosis were associated with lower (greater disease) scores. CONCLUSION:
      The evaluation of radiographs using the Brasfield score demonstrated the most
      important pulmonary findings in cystic fibrosis and identified the age group when
      these alterations began to appear more pronounced.

PMID- 25048733
TI  - The figure-of-eight artifact in the echocardiographic assessment of percutaneous
      disc occluders: impact of imaging depth and device type.
AB  - PURPOSE: Echocardiography is increasingly important in the guidance and follow-up
      of percutaneous transcatheter device closures. It was recently shown that the
      Amplatzer left atrial appendage occluder frequently presents as a figure-of-eight
      artifact due to interaction of device mesh and ultrasound waves. It remains
      unknown whether this can be translated to other types of disc occluders.
      Furthermore, the morphology of this figure-of-eight artifact appears to be
      different in the transesophageal and transthoracic image of the same device. The
      aim of this study was to evaluate the echocardiographic appearance of different
      types of disc occluders, and to clarify differences in morphology of the figure
      of-eight artifact. METHODS: A mathematical model of an epitrochoid curve was used
      for numerical simulation of disc occluder appearance at various imaging depths.
      In addition, an in vitro setup was used for echocardiographic analysis of
      different types of disc occluders at adjustable imaging depth and position.
      RESULTS: Mathematically, decreasing the imaging depth resulted in a more
      asymmetric figure-of-eight, i.e. with small upper part and wide lower part. In
      vitro results were in close agreement with the mathematical results. In addition,
      in vitro a figure-of-eight artifact was obtained in all different types of disc
      occluder devices. CONCLUSIONS: Different types of percutaneous disc occluders all
      present as a figure-of-eight artifact on echocardiography when imaged from a
      coronal imaging position. The morphology of the artifact depends on the imaging
      depth, with a more asymmetric figure-of-eight morphology at smaller probe-to
      device distance. This clarifies the differences observed between transesophageal
      and transthoracic imaging.

PMID- 25048734
TI  - Two sisters reveal autosomal recessive inheritance of epidermodysplasia
      verruciformis: a case report.
AB  - BACKGROUND: Epidermodysplasia verruciformis is a rare genodermatosis
      characterized by a unique susceptibility to cutaneous human papillomaviruses
      infection. Most patients show autosomal recessive patterns of inheritance. CASE
      PRESENTATION: We report a case of two sisters with clinically epidermodysplasia
      verruciformis specific lesions on the face, neck, trunk, and extremities. PCR
      analysis indicated the presence of human papillomavirus type 5 in the lesions.
      Electron microscopic examination showed viral-like particles in keratinocyte
      nuclei and the stratum corneum of the epidermodysplasia verruciformis lesions. In
      addition, we examined the EVER1 and EVER2 genes using eight different primer
      pairs without finding any nonsense or frameshift mutations in the gDNA from
      lymphocytes of the elder sister. CONCLUSIONS: In this report, the patient's
      parents did not have epidermodysplasia verruciformis lesions or a consanguineous
      marriage. EV did not develop in the elder sister until five years of age, so the
      parents did not perceive EV as an inherited disease. The probability that EV
      developed in both sisters was only 6.25%. Thus, it is rare for both sisters to
      develop epidermodysplasia verruciformis lesions considering that the parents were
      presumed to be carriers and the disease reveal an autosomal recessive pattern of
      inheritance.

PMID- 25048736
TI  - A k-NN algorithm for predicting the oral sub-chronic toxicity in the rat.
AB  - Repeated dose toxicity is of the utmost importance to characterize the
      toxicological profile of a chemical after repeated administration. Its evaluation
      refers to the Lowest-Observed-(Adverse)-Effect-Level (LO(A)EL) explicitly
      requested in several regulatory contexts, such as REACH and EC Regulation
      1223/2009 on cosmetic products. So far in vivo tests have been the sole viable
      option to assess repeated dose toxicity. We report a customized k-Nearest
      Neighbors approach for predicting sub-chronic oral toxicity in rats. A training
      set of 254 chemicals was used to derive models whose robustness was challenged
      through leave-one-out cross-validation. Their predictive power was evaluated on
      an external dataset comprising 179 chemicals. Despite the intrinsically
      heterogeneous nature of the data, our models give promising results, with
      q2>=0.632 and external r2>=0.543. The confidence in prediction was ensured by
      implementing restrictive user-adjustable rules excluding suspicious chemicals
      irrespective of the goodness in their prediction. Comparison with the very few
      LO(A)EL predictive models in the literature indicates that the results of the
      present analysis can be valuable in prioritizing the safety assessment of
      chemicals and thus making safe decisions and justifying waiving animal tests
      according to current regulations concerning chemical safety.

PMID- 25048735
TI  - Multi-tissue omics analyses reveal molecular regulatory networks for puberty in
      composite beef cattle.
AB  - Puberty is a complex physiological event by which animals mature into an adult
      capable of sexual reproduction. In order to enhance our understanding of the
      genes and regulatory pathways and networks involved in puberty, we characterized
      the transcriptome of five reproductive tissues (i.e. hypothalamus, pituitary
      gland, ovary, uterus, and endometrium) as well as tissues known to be relevant to
      growth and metabolism needed to achieve puberty (i.e., longissimus dorsi muscle,
      adipose, and liver). These tissues were collected from pre- and post-pubertal
      Brangus heifers (3/8 Brahman; Bos indicus x 5/8 Angus; Bos taurus) derived from a
      population of cattle used to identify quantitative trait loci associated with
      fertility traits (i.e., age of first observed corpus luteum (ACL), first service
      conception (FSC), and heifer pregnancy (HPG)). In order to exploit the power of
      complementary omics analyses, pre- and post-puberty co-expression gene networks
      were constructed by combining the results from genome-wide association studies
      (GWAS), RNA-Seq, and bovine transcription factors. Eight tissues among pre
      pubertal and post-pubertal Brangus heifers revealed 1,515 differentially
      expressed and 943 tissue-specific genes within the 17,832 genes confirmed by RNA
      Seq analysis. The hypothalamus experienced the most notable up-regulation of
      genes via puberty (i.e., 204 out of 275 genes). Combining the results of GWAS and
      RNA-Seq, we identified 25 loci containing a single nucleotide polymorphism (SNP)
      associated with ACL, FSC, and (or) HPG. Seventeen of these SNP were within a gene
      and 13 of the genes were expressed in uterus or endometrium. Multi-tissue omics
      analyses revealed 2,450 co-expressed genes relative to puberty. The pre-pubertal
      network had 372,861 connections whereas the post-pubertal network had 328,357
      connections. A sub-network from this process revealed key transcriptional
      regulators (i.e., PITX2, FOXA1, DACH2, PROP1, SIX6, etc.). Results from these
      multi-tissue omics analyses improve understanding of the number of genes and
      their complex interactions for puberty in cattle. 

PMID- 25048737
TI  - Threshold effects in nonlinear models with an application to the social capital
      retirement-health relationship.
AB  - This paper considers the relationship between social capital and health in the
      years before, at and after retirement. This adds to the current literature that
      only investigates this relationship in either the population as a whole or two
      subpopulations, pre-retirement and post-retirement. We now investigate if there
      are further additional subpopulations in the years to and from retirement. We
      take an information criteria approach to select the optimal model of
      subpopulations from a full range of potential models. This approach is similar to
      that proposed for linear models. Our contribution is to show how this may also be
      applied to nonlinear models and without the need for estimating subsequent
      subpopulations conditional on previous fixed subpopulations. Our main finding is
      that the association of social capital with health diminishes at retirement, and
      this decreases further 10 years after retirement. We find a strong positive
      significant association of social capital with health, although this turns
      negative after 20 years, indicating potential unobserved heterogeneity. The types
      of social capital may differ in later years (e.g., less volunteering) and hence
      overall social capital may have less of an influence on health in later years.

PMID- 25048738
TI  - Correlation of striatal dopamine transporter imaging with post mortem substantia
      nigra cell counts.
AB  - Dopamine transporter imaging is widely used for the differential diagnosis of
      parkinsonism. Only limited data are available on the relationship between
      striatal dopamine transporter binding and dopaminergic cell loss in the
      substantia nigra (SN). We analyzed postmortem SN cell counts in patients who had
      previously undergone dopamine transporter single-photon emission computed
      tomography (SPECT). Pathological diagnoses included Parkinson's disease (n = 1),
      dementia with Lewy bodies (n = 2), multiple system atrophy (n = 1), corticobasal
      degeneration (n = 2), atypical parkinsonism with multiple pathological conditions
      (n = 1), Alzheimer's disease (n = 1), and Creutzfeldt-Jakob disease (n = 1).
      [(12) (3) I]beta-CIT SPECT had been performed in all subjects using a
      standardized protocol on the same triple-head gamma camera. The density of
      neuromelanin-containing and tyrosine hydroxylase-positive substantia nigra
      neurons/mm(2) was evaluated in paraffin-embedded tissue sections by morphometric
      methods. Mean disease duration at the time of dopamine transporter imaging was
      2.3 years, and the mean interval from imaging to death was 29.3 months (range, 4
      68 months). Visual analysis of dopamine transporter images showed reduced
      striatal uptake in all seven patients with neurodegenerative parkinsonism, but
      not in Alzheimer's and Creutzfeldt-Jakob disease cases. Averaged [(right+left)/2]
      striatal uptake was highly correlated with averaged SN cell counts (rs  = 0.98, P
      < 0.0005 for neuromelanin- and rs  = 0.96, P < 0.0005 for tyrosine hydroxylase
      positive cells). Similar strong correlations were found in separate analyses for
      the right and left sides. Striatal dopamine transporter binding highly correlated
      with postmortem SN cell counts, confirming the validity of dopamine transporter
      imaging as an excellent in vivo marker of nigrostriatal dopaminergic
      degeneration.

PMID- 25048739
TI  - Collective synthesis of 4-hydroxy-2-pyridone alkaloids and their
      antiproliferation activities.
AB  - A collective synthesis of 4-hydroxy-2-pyridone alkaloids--specifically,
      pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and
      torrubiellone C--has been achieved. Key steps include using a strategic
      convergent method to synthesize the densely substituted pyridone key intermediate
      by Suzuki-Miyaura cross-coupling reaction, a divergent synthesis approach of
      target molecules by aldol condensation of pyridone intermediate with homologous
      aldehydes, and an iterative synthesis of homologous aldehydes with all-trans
      polyene backbones. Interestingly, among the six tumor cell lines investigated,
      torrubiellone C was found to induce potent and apoptotic inhibitory activities on
      Jurkat T cells with IC50 values of 7.05 MUM. Hence, this approach could
      potentially contribute to the synthesis of bioactive small-molecule libraries as
      well as drug discovery.

PMID- 25048740
TI  - Are men at greater risk of lean mass deficits in rheumatoid arthritis?
AB  - OBJECTIVE: We aimed to determine if there were sex differences in lean body mass
      (LBM) in patients with rheumatoid arthritis (RA) when compared with sex- and race
      specific National Health and Nutrition Examination Survey (NHANES) reference
      data, and to investigate the impact of sex differences in risk factors for LBM
      deficits. METHODS: Dual x-ray absorptiometry measures of whole body LBM and
      appendicular LBM (arms and legs, appendicular lean mass [ALM]) were obtained on a
      total of 190 subjects from 2 independent cohorts (141 from San Francisco [SF], 49
      from Philadelphia [PA]), expressed as indices adjusted for height (LBM index and
      ALM index, kg/m(2) ), and converted to sex- and race-specific Z scores relative
      to age and based on NHANES data. Sarcopenia was defined using 4 different sex
      specific definitions. Multivariable linear and logistic regression analyses
      adjusted for disease activity, disease duration, physical activity, anti-cyclic
      citrullinated peptide seropositivity, fat mass index, and glucocorticoid use.
      RESULTS: While there were significant differences between the 2 cohorts, ALM
      index Z scores were significantly lower in men compared to women in both (SF: 
      1.43 versus -0.43, P < 0.0001; PA: -0.83 versus -0.06, P = 0.03). Observed sex
      differences were significant after adjustment in multivariable analyses within
      both cohorts. Odds of sarcopenia were 3 to 8 times greater in men in the SF
      cohort. Men in the PA cohort also had a higher, but nonsignificant, risk of
      sarcopenia. CONCLUSION: RA is associated with significant LBM deficits, with
      greater deficits observed in men. Future study may help elucidate the mechanisms
      driving greater deficits among men.

PMID- 25048741
TI  - Endophytic bacterial community of grapevine leaves influenced by sampling date
      and phytoplasma infection process.
AB  - BACKGROUND: Endophytic bacteria benefit host plant directly or indirectly, e.g.
      by biocontrol of the pathogens. Up to now, their interactions with the host and
      with other microorganisms are poorly understood. Consequently, a crucial step for
      improving the knowledge of those relationships is to determine if pathogens or
      plant growing season influence endophytic bacterial diversity and dynamic.
      RESULTS: Four healthy, four phytoplasma diseased and four recovered (symptomatic
      plants that spontaneously regain a healthy condition) grapevine plants were
      sampled monthly from June to October 2010 in a vineyard in north-western Italy.
      Metagenomic DNA was extracted from sterilized leaves and the endophytic bacterial
      community dynamic and diversity were analyzed by taxon specific real-time PCR,
      Length-Heterogeneity PCR and genus-specific PCR. These analyses revealed that
      both sampling date and phytoplasma infection influenced the endophytic bacterial
      composition. Interestingly, in June, when the plants are symptomless and the
      pathogen is undetectable (i) the endophytic bacterial community associated with
      diseased grapevines was different from those in the other sampling dates, when
      the phytoplasmas are detectable inside samples; (ii) the microbial community
      associated with recovered plants differs from that living inside healthy and
      diseased plants. Interestingly, LH-PCR database identified bacteria previously
      reported as biocontrol agents in the examined grapevines. Of these, Burkholderia,
      Methylobacterium and Pantoea dynamic was influenced by the phytoplasma infection
      process and seasonality. CONCLUSION: Results indicated that endophytic bacterial
      community composition in grapevine is correlated to both phytoplasma infection
      and sampling date. For the first time, data underlined that, in diseased plants,
      the pathogen infection process can decrease the impact of seasonality on
      community dynamic. Moreover, based on experimental evidences, it was reasonable
      to hypothesize that after recovery the restructured microbial community could
      maintain the main structure between seasons.

PMID- 25048742
TI  - Infection control practice: interview with 20 nurses reveals themes of
      rationalising their own behaviour and justifying any deviations from policy.
AB  - Implications for practice and research: Infection prevention involves complex
      social behaviour. Education is unlikely to be sufficient when seeking to improve
      nurses' infection prevention practice. Multifaceted campaigns that include
      education are more likely to be effective. Further research is needed to identify
      the beliefs held by other health workers about healthcare-associated infection.

PMID- 25048743
TI  - Pain characteristics in fibromyalgia: understanding the multiple dimensions of
      pain.
AB  - Fibromyalgia is a common disease with a high economic burden. The etiology of
      this disease remains unclear, as there are no specific abnormalities on clinical
      or technical examinations. Evidence suggests that central pain sensitization at
      the brain pain matrix might be involved. Understanding the pain characteristics
      of this disease is of importance both for diagnosis and treatment. The authors
      present their findings of pain characteristics in a Belgium population of
      fibromyalgia patients. Data of 65 patients (57 male and 8 female patients) were
      analyzed in this study (mean age 46.86, SD = +8.79). Patients filled out the
      following questionnaires: visual analogue scale, fibromyalgia impact
      questionnaire, pain-catastrophizing scale, pain vigilance and awareness
      questionnaire, modified fatigue impact scale, the Beck depression inventory, the
      short form 36 and the Dutch shortened profile of mood states. Statistical
      analysis was performed making use of a factor analysis and a hierarchical cluster
      analysis. We were able to define pain characteristics in this group of patients.
      The reciprocal effects of mood and fatigue on pain experience could be identified
      within the data, catastrophizing scores show a high correlation with overall life
      quality and pain experience. We have performed a cluster analysis on the
      fibromyalgia patients, based on the four main principal components defining the
      overall disease burden. Mood explained most of the variance in symptoms, followed
      by mental health state, fatigue, and catastrophizing. Three clusters of patients
      could be revealed by these components. Clusters: 1 high scores on mood disorders,
      pain, and decreased mental health, 2 high scores on fatigue and physical health,
      and 3 a mixture of these two groups. This data suggest that different subgroups
      of fibromyalgia patients could be identified and based on that, treatment
      strategies and results might be adapted.

PMID- 25048744
TI  - Switching from allopurinol to febuxostat for the treatment of hyperuricemia and
      renal function in patients with chronic kidney disease.
AB  - Hyperuricemia is a frequent complication of chronic kidney disease (CKD).
      Febuxostat is a novel xanthine oxidase inhibitor that is metabolized by many
      metabolic pathways in the kidney and the liver. We performed a 1-year cohort
      study of 73 hyperuricemic patients who had an estimated glomerular filtration
      rate (eGFR) below 45 ml/min and were being treated with urate-lowering therapy.
      In 51 patients, treatment was changed from allopurinol to febuxostat, and the
      other 22 patients were continued on allopurinol. The serum levels of uric acid
      (UA) level, creatinine, and other biochemical parameters were measured at
      baseline and after 3, 6, 9, and 12 months of treatment. The serum UA levels
      significantly decreased from 6.1 +/- 1.0 to 5.7 +/- 1.2 mg/dl in the febuxostat
      group and significantly increased from 6.2 +/- 1.1 to 6.6 +/- 1.1 mg/dl in the
      allopurinol group. The eGFR decreased 27.3 to 25.7 ml/min in the febuxostat group
      and from 26.1 to 19.9 ml/min in the allopurinol group. The switch from
      allopurinol to febuxostat was significantly associated with the changes in eGFR
      according to a multiple regression analysis (beta = -0.22145, P < 0.05).
      Febuxostat reduced the serum UA levels and slowed the progression of renal
      disease in our CKD cohort in comparison with allopurinol. 

PMID- 25048745
TI  - Initial experience with non-invasive prenatal testing of cell-free DNA for major
      chromosomal anomalies in a clinical setting.
AB  - OBJECTIVE: To evaluate non-invasive prenatal testing (NIPT) of cell-free DNA
      (cfDNA) as a screening method for major chromosomal anomalies (CA) in a clinical
      setting. METHODS: From January to December 2013, PanoramaTM test or HarmonyTM
      prenatal test were offered as advanced NIPT, in addition to first-trimester
      combined screening in singleton pregnancies. RESULTS: The cohort included 333
      pregnant women with a mean maternal age (MA) of 37 years who underwent testing at
      a mean gestational age of 14.6 weeks. Eighty-four percent were low-risk
      pregnancies. Results were provided in 97.3% of patients at a mean reporting time
      of 12.9 calendar days. Repeat sampling was performed in six cases and results
      were obtained in five of them. No results were provided in four cases. Four cases
      of Down syndrome were detected and there was one discordant result of Turner
      syndrome. We found no statistical differences between commercial tests except in
      reporting time, fetal fraction and MA. The cfDNA fraction was statistically
      associated with test type, maternal weight, BMI and log betahCG levels.
      CONCLUSIONS: NIPT has the potential to be a highly effective screening method for
      major CA in a clinical setting.

PMID- 25048746
TI  - Representativeness of enrollment into a perinatal research repository.
AB  - OBJECTIVE: To describe enrollment and compare demographic and clinical
      characteristics of neonates enrolled in the perinatal research repository (PRR)
      with eligible, but non-enrolled neonates. METHODS: Characteristics from enrolled
      infants were compared with eligible, but non-enrolled infants using t-tests,
      Wilcoxon rank tests and chi(2) tests. RESULTS: Between 1 January 2010 and 31
      December 2011, 622 infants admitted to the neonatal intensive care unit (NICU),
      born < 37 weeks were screened for the PRR were eligible for enrollment. Of these,
      233 enrolled in the study. There were no significant differences between enrolled
      and non-enrolled infants with regard to race, birth weight, gestational age and
      Apgar scores. Enrolled patients had a significantly longer length of stay [mean
      (standard deviation) = 55.0 (58.9) versus 38.0 (45.8) days; p < 0.01]. Mortality
      was significantly greater in the non-enrolled group (11.7 versus 3.0%; p < 0.01).
      Both groups had a similar total number of diagnoses [mean (standard deviation) =
      5.7 (3.1) versus 5.8 (3.2)]; however, among survivors enrolled infants had
      slightly lower prevalence of hypoxic ischemic encephalopathy (0.0 versus 2.9%; p
      < 0.01) and seizures (1.8 versus 6.4%; p < 0.01). There were no significant
      differences in enrollment by prevalence of other morbidities. CONCLUSIONS: These
      results suggest that a specimen collecting repository can enroll a sufficiently
      representative sample of eligible patients.

PMID- 25048747
TI  - Salivary progesterone and cervical length measurement as predictors of
      spontaneous preterm birth.
AB  - OBJECTIVE: To evaluate the efficacy of salivary progesterone, cervical length
      measurement in predicting preterm birth (PTB). METHODS: Prospective observational
      study included 240 pregnant women with gestational age (GA) 26-34 weeks
      classified into two equal groups; group one are high risk for PTB (those with
      symptoms of uterine contractions or history of one or more spontaneous preterm
      delivery or second trimester abortion) and group 2 are controls. RESULTS: There
      was a highly significant difference between the two study groups regarding GA at
      delivery (31.3 +/- 3.75 in high risk versus 38.5 +/- 1.3 in control), cervical
      length measured by transvaginal ultrasound (24.7 +/- 8.6 in high risk versus 40.1
      +/- 4.67 in control) and salivary progesterone level (728.9 +/- 222.3 in high
      risk versus 1099.9 +/- 189.4 in control; p < 0.001). There was a statistically
      significant difference between levels of salivary progesterone at different GA
      among the high risk group (p value 0.035) but not in low risk group (p value
      0.492). CL measurement showed a sensitivity of 71.5% with 100% specificity, 100%
      PPV, 69.97% NPV and accuracy of 83%, while salivary progesterone showed a
      sensitivity of 84% with 90% specificity, 89.8% PPV, 85.9% NPV and accuracy of
      92.2%. CONCLUSION: The measurement of both salivary progesterone and cervical
      length are good predictors for development of PTB.

PMID- 25048748
TI  - Can we improve the targeting of respiratory syncytial virus (RSV) prophylaxis in
      infants born 32-35 weeks' gestational age with more informed use of risk factors?
AB  - OBJECTIVE: To evaluate the key risk factors for respiratory syncytial virus (RSV)
      hospitalisation in 32-35 weeks' gestational age (wGA) infants. METHODS: Published
      risk factors were assessed for predictive accuracy (area under the receiver
      operating characteristic curve [ROC AUC]) and for number needed to treat (NNT).
      RESULTS: Key risk factors included: proximity of birth to the RSV season; having
      siblings; crowding at home; day care; smoking; breast feeding; small for GA; male
      gender; and familial wheezing/eczema. Proximity of birth to the RSV season
      appeared the most predictive. Risk factors models from Europe and Canada were
      found to have a high level of predictive accuracy (ROC AUC both > 0.75; NNT for
      European model 9.5). A model optimised for three risk factors (birth +/- 10 weeks
      from start of RSV season, number of siblings >= 2 years and breast feeding for <=
      2 months) had a similar level of prediction (ROC AUC: 0.776; NNT: 10.2). An
      example two-risk factor model (day care attendance and living with >= 2 siblings
      < 5 years old) had a lower level of predictive accuracy (ROC AUC: 0.55; NNT: 26).
      CONCLUSIONS: An optimised combination of risk factors has the potential to
      improve the identification of 32-35 wGA infants at heightened risk of RSV
      hospitalisation.

PMID- 25048749
TI  - Calponin levels in term laboring women.
AB  - OBJECTIVE: Calponin, a specific smooth muscle contraction regulatory troponin
      like protein, is present in large quantities in uterine smooth muscle. Serum
      troponin levels rise in acute myocardial infarction, and creatine phosphokinase
      levels rise at high physical activity, both due to destruction of cardiac and
      striated muscle fibers. We hypothesize that the active labor process may cause
      uterine smooth muscle cell damage, which may result in rising maternal serum
      calponin levels. This was a preliminary study, searching for a new biomarker for
      preterm labor. METHODS: The study group included laboring term primiparous women
      with a singleton fetus. The control group included similar demographic and
      pregnancy characteristics pregnant women not in labor. Maternal serum levels of
      calponin basic isoform were measured evaluated and compared in both groups.
      RESULTS: Study group included 100 pregnant women. Calponin serum levels were
      higher in the active labor (794 +/- 974 ng/mL) than in the group not in labor
      (591 +/- 587 ng/mL), although it did not reach statistical significance. Gender
      and neonatal weight were similar in the two study groups. CONCLUSIONS: Calponin
      serum levels showed moderate elevation during active labor, compared to the
      levels in a cohort of pregnant comparable women at the same gestational weeks but
      not in labor.

PMID- 25048750
TI  - Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese
      women or when initiated early in pregnancy?
AB  - OBJECTIVE: Late timing of intervention and maternal obesity are potential
      explanations for the modest effect of aspirin for preeclampsia prevention. We
      explored whether low-dose aspirin (LDA) is more effective in women at increased
      risk when initiated before 16 weeks' gestation or given to non-obese women.
      METHODS: Secondary analysis of a trial to evaluate LDA (60 mg/d) for preeclampsia
      prevention in high-risk women. Participants were randomized to LDA or placebo
      between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a)
      timing of randomization (< 16 or >= 16 weeks gestation) and (b) body mass index
      (BMI) class (non-obese and obese). The Breslow-Day test for homogeneity was used
      to assess for variations in effect of LDA across gestational age and BMI groups.
      RESULTS: Of 2503 women, 461 (18.4%) initiated LDA < 16 weeks. LDA effect was not
      better when initiated < 16 weeks (RR: 0.93, 95% CI: 0.67-1.31) versus >= 16 weeks
      (RR: 0.90, 95% CI: 0.75-1.08), (p value for interaction = 0.87). Similarly, LDA
      effect was not better in non-obese (RR: 0.91, 95% CI: 0.7-1.13) versus obese
      women (RR: 0.89, 95% CI: 0.7-1.13), (p value for interaction = 0.85). CONCLUSION:
      LDA for preeclampsia prevention was not more effective when initiated < 16 weeks
      or used in non-obese women at risk for preeclampsia. No particular subgroup of
      women was more or less likely to benefit from LDA therapy.

PMID- 25048751
TI  - Transcervical Foley's catheter versus Cook balloon for cervical ripening in
      stillbirth with a scarred uterus: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy and safety of the use of transcervical Foley's
      catheter versus Cook cervical ripening balloon in pregnant women with stillbirth,
      unfavorable cervix and scarred uterus. DESIGN: Randomized controlled study.
      SETTING: El Minia University Hospital, El Minia, Egypt. PATIENTS AND METHODS: Two
      hundred pregnant women with stillbirth, unfavorable cervix and scarred uterus
      were recruited into this study. They were randomized into two groups. In group I
      (n = 100), cervical ripening was done using Foley's catheter. In group II (n =
      100), cervical ripening was done using Cook cervical ripening balloon. MAIN
      OUTCOME MEASURES: Balloon insertion to delivery interval, successful ripening
      rate, cesarean delivery rate, maternal adverse events and maternal satisfaction.
      RESULTS: Time from balloon insertion to expulsion and from balloon insertion to
      delivery was significantly shorter in Foley's catheter group. However, the
      difference between the two groups regarding time from balloon insertion to active
      labor, time from balloon expulsion to delivery, cervical ripening, cesarean
      section, instrumental delivery, pain score, need for analgesia, hospital stay and
      maternal satisfaction was not statistically significant. CONCLUSIONS: Foley's
      catheter and Cook cervical ripening balloon are comparable regarding efficacy and
      safety profile when used to ripen the cervix in pregnant women with stillbirth,
      unfavorable cervix and scarred uterus. However, Foley's catheter has a shorter
      induction to delivery interval and is relatively cheaper device.

PMID- 25048752
TI  - Pentraxin 3 concentrations of the mothers with preterm premature rupture of
      membranes and their neonates, and early neonatal outcome.
AB  - BACKGROUND: Pentraxin 3 (PTX3) is an acute phase reactant which has been used to
      detect intra-amniotic infections (IAI) in pregnancy, but the prognostic value of
      PTX3 concentrations on neonates has not been studied. We aimed to investigate the
      relationship between maternal PTX3-neonatal PTX3 concentrations and early
      neonatal outcome. METHODS: The mothers diagnosed with preterm prelabor rupture of
      membranes (PPROM) (n = 28) and their preterm infants (n = 28) were included in
      the study. PTX3 concentrations were studied in plasma in the maternal peripheral
      blood and umbilical/peripheral vein in the neonates. The relationship between the
      mPTX3-nPTX3 concentrations and neonatal outcome were investigated using non
      parametric tests and binary logistic regression analysis. RESULTS: The mean mPTX3
      concentration was 10.35 +/- 7.82 MUg/L. Ten (35.7%) of all mothers were within
      the normal range and 18 (64.3%) in high percentile (>= 97.5 percentile). There
      was no relation between mPTX3 concentrations and clinical or histologic
      chorioamnionitis, latency of PPROM, and early neonatal outcome. Mean nPTX3
      concentrations was 9.18 +/- 7.83 MUg/L and high nPTX3 concentrations were
      detected in five (17.8%) neonates. nPTX3 concentrations were inversely correlated
      with gestational age and correlated with rate of intraventricular hemorrhage
      (IVH) and mortality. Neonates with high nPTX3 concentrations also have lowered
      APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis,
      IVH, necrotizing enterocolitis and prolonged NICU stay. CONCLUSION: High PTX3
      concentrations of the newborns are associated with some worsened early neonatal
      outcome including lower gestational age at delivery, increased rate of IVH and
      mortality. Maternal PTX3 concentrations are not an adequate marker in defining
      clinical or histologic chorioamnionitis and early neonatal outcome.

PMID- 25048753
TI  - Impact of amniotic fluid "sludge" on the risk of preterm delivery.
AB  - OBJECTIVE: To evaluate the impact of amniotic fluid "sludge" (AFS) on the risk of
      preterm delivery and to describe the effect of antibiotic treatment in that
      situation. METHODS: Case-control study including singleton pregnancies with or
      without AFS, between 15-32 weeks of gestation. Factors associated with preterm
      delivery before 32 weeks, 34 weeks and 37 weeks were evaluated with univariate
      and multivariate logistic regression. Since all women with AFS in this study were
      treated with antibiotics, a historical comparison was performed with similar
      patients with AFS found before 2007 and not treated with antibiotics. RESULTS:
      AFS was observed in 90/1220 patients (7.4%). AFS was associated with shorter
      cervical length, greater body mass index, cervical cerclage and preterm birth
      before 28 weeks. However, after adjustment, AFS did not remain associated with
      preterm delivery before 32 or 34 weeks. The historical comparison suggested that
      azithromycin could significantly reduce the risk of preterm delivery before 34
      weeks (odds ratio: 0.2; 95% CI: 0.04-0.92). CONCLUSIONS: AFS, treated with
      azithromycin, was associated with a higher risk of prematurity, but not
      independently after adjustment for cervical length and second trimester vaginal
      bleeding. Further studies need to evaluate the effect of antibiotics in
      pregnancies with AFS.

PMID- 25048754
TI  - Criterion validity of the Strengths and Difficulties Questionnaire (SDQ) with
      inpatient adolescents.
AB  - Increasing rates of adolescent admissions to inpatient psychiatric settings and
      acute length of stay necessitates valid psychiatric screening tools. The
      Strengths and Difficulties Questionnaire (SDQ) appears to have valuable clinical
      application due to its brevity and strong psychometric properties. In this study
      we aimed to evaluate the criterion validity of the SDQ in 159 psychiatric
      inpatients between the ages of 12-17 against the Computerized Diagnostic
      Interview Schedule for Children (CDISC). In determining the criterion validity of
      the SDQ against the CDISC-IV, we further sought to compare its classification
      accuracy with the DSM-oriented scales of two widely-used clinical screeners for
      children and adolescents, the Child Behavior Checklist (CBCL) and Youth Self
      Report (YSR). Results demonstrated comparable diagnostic accuracy for the three
      measures in detecting common emotional and behavioral disorders. Tentative
      clinical cutoffs were proposed specific to American adolescents for parent and
      youth reports. Sensitivity and specificity values are also reported and
      discussed. 

PMID- 25048755
TI  - Detecting motion signals of intent in schizophrenia.
AB  - Twenty-four patients with schizophrenia and 18 controls detected chasing in
      displays of moving disks. Compared to controls, patients had relatively higher
      hit rates for less direct compared to more direct chasing trials. Perceiving
      intent was generally intact in patients, despite the well-known difficulties with
      inferring intentional mental states in schizophrenia. 

PMID- 25048756
TI  - Predictors of help-seeking for suicidal ideation in the community: risks and
      opportunities for public suicide prevention campaigns.
AB  - Help-seeking behaviour for suicidality is low and the reasons for this have not
      systematically been examined. The aim of the current study was to examine the
      relationship between suicide stigma, suicide literacy and help-seeking attitudes
      and intentions. One thousand two hundred seventy-four Australian adults recruited
      via Facebook completed an online survey assessing a range of mental health
      outcomes. High suicide literacy and low suicide stigma were significantly
      associated with more positive help-seeking attitudes and, among a subsample of
      534, greater intentions to seek help. Attribution of suicide to isolation was
      associated with more positive attitudes toward help-seeking and greater
      intentions to seek help, while respondents experiencing suicidal ideation had
      more negative attitudes toward help-seeking and lower intentions to seek help.
      Lower depressive symptoms, older age and female gender were associated with more
      positive help-seeking attitudes and higher help-seeking intentions. However,
      there were differential associations of specific suicide knowledge items and
      specific stigmatising attitudes with help-seeking outcomes; suggesting a nuanced
      approach may be required to promote help seeking for suicidality. Suicide
      knowledge and attitudes play an important role in the help-seeking process for
      suicide and should be carefully considered in the development of public awareness
      campaigns. 

PMID- 25048757
TI  - Rapid spread of suicide by charcoal burning from 2007 to 2011 in Korea.
AB  - Despite rapid increase of suicide by charcoal burning within 5 years, little is
      known about the characteristics of charcoal burning suicide in Korea. This study
      aimed to examine the trends and risk factors in the spread of suicide using this
      method. We identified an association between media reporting of suicide by
      charcoal burning and its incidence. Data on suicide from 2007 to 2011 were
      obtained from the Korean National Statistical Office. Cross-correlation analysis
      was used. Increasing incidence of suicide by charcoal burning was correlated with
      higher education levels, male sex, and the latter half of the year. Victims of
      charcoal burning suicide were more likely to be young, male, single, highly
      educated, professional, urban-based, and to die between October and December.
      Internet reports of suicide via charcoal burning tended to precede the increased
      incidence of suicide using this method, but only during the early period of the
      suicide epidemic. Our findings suggest that one episode of heavy media coverage
      of a novel method, such as charcoal burning, is sufficient to increase the
      prevalence of suicide by that method even after media coverage decreases. These
      findings are expected to contribute to the prevention of increasing rates of
      suicide by charcoal burning. 

PMID- 25048758
TI  - Social approach and avoidance behaviour for negative emotions is modulated by
      endogenous oxytocin and paranoia in schizophrenia.
AB  - Patients with schizophrenia suffer from dysfunctional social behaviour. Social
      approach and avoidance (AA) has been associated with motor responses, as the
      affective valence and gaze direction of facial stimuli can bias push and pull
      motor tendencies. The aim of this study was to investigate the role of endogenous
      oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels
      were collected from 28 patients who were then given a joystick-based Approach
      Avoidance Task (AAT). Reaction times were recorded and AAT effect scores
      calculated for responses to happy and angry faces, which either had direct or
      averted gaze. Individual differences in basal oxytocin had a significant
      relationship with AAT responses, and patients with higher levels of oxytocin
      tended to avoid angry faces more. Furthermore, greater avoidance of angry faces
      was correlated with more severe psychotic (positive and general) symptoms and
      greater paranoia. This suggests that the endogenous effects of oxytocin may be
      specific to the interpretation of negative threatening emotions in schizophrenia
      patients, and also provides evidence that psychotic symptoms and paranoia can
      impact on social AA behaviour by heightening threat avoidance. 

PMID- 25048760
TI  - Association between VNTR polymorphism in promoter region of prodynorphin (PDYN)
      gene and heroin dependence.
AB  - Within the core promoter region of prodynorphin (PDYN), a 68-bp sequence was
      found to occur as a polymorphism element, either singular or as tandemly repeated
      two, three or four times. We report the sequence of a novel allele (5-repeats).
      Our study revealed the existence of an ancestral nucleotide (A) at 29th position
      of the VNTR in human. In total, 442 heroin addicts and 799 controls were included
      in this study. The present findings revealed a male-limited association between
      VNTR polymorphism and heroin dependence risk. 

PMID- 25048759
TI  - The content of attenuated psychotic symptoms in those at clinical high risk for
      psychosis.
AB  - Recent research has started to focus on identifying individuals who are at
      clinical high risk of developing psychosis as a means to try and understand the
      predictors and mechanisms involved in the progress to a full psychotic episode.
      The aim of the current study was to provide an initial description and prevalence
      rates of specific content found within attenuated positive symptoms. The Content
      of Attenuated Positive Symptoms (CAPS) codebook was used by independent raters to
      determine the presence of content within a sample of written vignettes.
      Krippendorff's alpha was used to determine inter-rater reliability. Overall, the
      majority of items fell in or above an acceptable range of reliability. There was
      heterogeneity present in the types of content endorsed. However, the most
      commonly endorsed items included being perplexed by reality, increased
      hypervigilence, being gifted, hearing indistinct and distinct sounds, seeing
      figures or shadows, something touching the individual, and unpleasant smells. The
      use of the CAPS codebook is a reliable way to code the content of attenuated
      positive symptoms. Identifying and monitoring the presence of certain content may
      provide insight into the presence of other comorbid issues and the potential for
      future conversion.

PMID- 25048761
TI  - Osteoarthritis: does post-injury ACL reconstruction prevent future OA?

PMID- 25048763
TI  - Ablation of frequent premature ventricular complex in an athlete.
AB  - Premature ventricular complex are common findings in the exam of many athletes.
      There is no extensive scientific evidence in the management of this situation
      particularly when associated with borderline contractile function of the left
      ventricle. In this case report, we present a 35-year-old asymptomatic healthy
      athlete with high incidence (over 10,000 beats in 24 h) of premature ventricular
      complex and left ventricular dilatation with dysfunction, which persisted after a
      resting period of 6 months without training. We performed radiofrequency ablation
      of the premature ventricular complex focus. After 1-year follow-up, he was
      asymptomatic without arrhythmia and the left ventricle normalized its size and
      function as shown by echocardiogram and cardiac magnetic resonance.

PMID- 25048764
TI  - Message from the editor in chief.

PMID- 25048762
TI  - The need to define treatment goals for systemic lupus erythematosus.
AB  - In the current therapeutic climate, mortality rates from systemic lupus
      erythematosus (SLE) remain unacceptably high. Although new therapies are on the
      horizon, pending their emergence and availability, optimization of the currently
      available therapies is potentially achievable. A 'treat-to-target' approach is
      now considered routine for many diseases, including rheumatoid arthritis, for
      which it has substantially improved patient outcomes. The heterogeneity of SLE,
      as well as lack of universal agreement over methods to measure disease activity
      and treatment responses, has impeded the development of such an approach for this
      disease. In this article, the potential benefits of a treatment-target definition
      are explored, obstacles to the development of a treatment target in SLE are
      identified, and possible strategies to achieve this goal are discussed. 

PMID- 25048765
TI  - Mobile photodynamic therapy unit for service to district general hospitals.

PMID- 25048766
TI  - Yorkshire Laser Centre mobile photodynamic therapy unit: For service to district
      general hospitals.
AB  - A mobile laser unit, principally for the provision of photodynamic therapy (PDT)
      services to District General Hospitals was designed and put into operation by the
      Yorkshire Laser Centre (YLC). The concept grew out of observation that the
      majority of patients who could potentially benefit from PDT are investigated and
      hospitalised in their District General Hospital (GDH) and not easily transferred
      to or treated and followed up by a PDT centre. Therefore, a mobile PDT unit
      (MPDTU) could facilitate the availability of PDT to patients on their "home
      ground" where they have been investigated and selected. The treatment is carried
      out at the host hospital by the patient's own local medical team assisted by the
      YLC through the MPDTU. Our MPDTU comprises of: During the past 3 years our MPDTU
      has had 43 sorties to six different hospitals in the region for PDT covering a
      variety of specialities. There has not been any failure of the organisation or
      operational system. CONCLUSIONS: The YLC model of MPDTU allows many more patients
      to benefit from this treatment who otherwise would be excluded from it because of
      lack of facilities and expertise locally at the patient's "home ground".

PMID- 25048767
TI  - Yorkshire Laser Centre mobile photodynamic therapy unit: For service to district
      general hospitals (Keyvan Moghissi & Kate Dixon).

PMID- 25048768
TI  - Methylene blue in photodynamic therapy: From basic mechanisms to clinical
      applications.
AB  - Methylene blue (MB) is a molecule that has been playing important roles in
      microbiology and pharmacology for some time. It has been widely used to stain
      living organisms, to treat methemoglobinemia, and lately it has been considered
      as a drug for photodynamic therapy (PDT). In this review, we start from the
      fundamental photophysical, photochemical and photobiological characteristics of
      this molecule and evolved to show in vitro and in vivo applications related to
      PDT. The clinical cases shown include treatments of basal cell carcinoma,
      Kaposi's Sarcoma, melanoma, virus and fungal infections. We concluded that used
      together with a recently developed continuous light source (RL50((r))), MB has
      the potential to treat a variety of cancerous and non-cancerous diseases, with
      low toxicity and no side effects. 

PMID- 25048769
TI  - Lipophilic cationic porphyrins as photodynamic sensitisers-Synthesis and
      structure-activity relationships.
AB  - A convenient synthesis of a range of phosphorous and nitrogen centred lipophilic
      cationic porphyrins is described. In vitro assays for photodynamic activity
      against human colorectal adenocarcinoma cells (HT-29) reveal significant
      differences based on substituents around the cation centres. 

PMID- 25048770
TI  - Photodynamic therapy for Barretts' adenocarcinoma associated with an Angelchik
      device.
AB  - We present a novel case of an elderly patient with a Barrett's adenocarcinoma in
      the presence of an Angelchik prosthesis. We aim to draw attention to issues
      relating to metaplastic Barretts' oesphagus and its adenocarcinoma complications
      and highlight relevant issues in multimodal endoscopic management and palliation
      using photodynamic therapy in the presence of the device. 

PMID- 25048771
TI  - Clinical photodynamic therapy of head and neck cancers-A review of applications
      and outcomes.
AB  - As local control is tantamount to cure in head and neck cancer, an aggressive
      regimen of surgery and radiation remains the standard of care for most patients.
      Despite significant technical advances, these treatments are highly morbid.
      Further, patients who fail treatment have limited salvage options. Photodynamic
      therapy (PDT) and photodiagnosis (PD) of head and neck cancer offer significant
      potential for improved outcomes in a myriad of clinical indications ranging from
      in situ to recurrent disease. However, despite promising results, these
      modalities remain at the fringe of head and neck treatment options.
      Photofrin((r)), Photosan and Foscan((r)) are photosensitizers used clinically in
      head and neck PD/PDT. In addition, aminolevulinic acid (ALA), which gives origin
      to Protoporphyrin IX, an endogeneous photosensitizer, is also used for PD/PDT. We
      review the clinical literature on these photosensitizers to assist in the
      integration of these important modalities into the mainstream of head and neck
      oncological therapy. 

PMID- 25048772
TI  - Photodiagnosis using Raman and surface enhanced Raman scattering of bodily
      fluids.
AB  - Raman spectroscopy is the measure of inelastic scatter and has been described
      since 1928. It is particularly useful for medical applications because the
      scattered radiation measured is unique for each biomolecule. The aim of this
      study was to review works published in Raman scattering and surface enhanced
      Raman scattering (SERS) on bodily fluids. The main Raman studies have
      concentrated on the detection of metabolites in the aqueous humour, urine and
      blood-based fluids and on drugs in the latter. Other bodily fluids are also
      studied, e.g. vitreous humour. The Raman intensity is inherently weak. SERS
      provides immense amplification of the Raman signal and so it can be used for the
      detection of small concentrations of biochemicals. This is achieved by using nano
      structured metal particles. Studies have been done to describe how the amino
      acids of bodily fluids interact with the nano-metal substrates. Applications of
      SERS in the medical field include: protein identification, illicit drugs in
      bodily fluids and its use as a reporter in immunoassay and DNA hybridisation. For
      both normal Raman and SERS the experimental design has also been reviewed. It
      clearly shows that the choice of wavelength is important to reduce the shot noise
      associated with fluorescence. Most experimental parameters show that these
      techniques can be useful and quick in vitro tests. 

PMID- 25048773
TI  - The influence of intracellular mTHPC concentration upon photobleaching dynamics.
AB  - In this study, we report the effect of the local photosensitizer concentration
      upon the dynamics of the singlet oxygen-mediated photobleaching, within formalin
      fixed keratinocytes. Although the cells were incubated at a single mTHPC dose,
      cell-to-cell variations in concentration were defined within the perinuclear
      region by differences in the initial amplitude of the laser-induced fluorescence
      emission, located around 652nm. At a fixed laser fluence-rate, it was found that
      the photobleaching, when plotted as a function of delivered light dose, proceeded
      more rapidly at higher drug concentration. The mTHPC spectral emission profile is
      shown to be approximately Lorentzian and remains unchanged as the photobleaching
      proceeds. This indicates that there is no perturbation of the detected signal due
      to the inner-filter effect. 

PMID- 25048774
TI  - Structural and functional properties of hemp seed protein products.
AB  - The effects of pH and protein concentration on some structural and functional
      properties of hemp seed protein isolate (HPI, 84.15% protein content) and
      defatted hemp seed protein meal (HPM, 44.32% protein content) were determined.
      The HPI had minimum protein solubility (PS) at pH 4.0, which increased as pH was
      decreased or increased. In contrast, the HPM had minimum PS at pH 3.0, which
      increased at higher pH values. Gel electrophoresis showed that some of the high
      molecular weight proteins (>45 kDa) present in HPM were not well extracted by the
      alkali and were absent or present in low ratio in the HPI polypeptide profile.
      The amino acid composition showed that the isolation process increased the
      Arg/Lys ratio of HPI (5.52%) when compared to HPM (3.35%). Intrinsic fluorescence
      and circular dichroism data indicate that the HPI proteins had a well-defined
      structure at pH 3.0, which was lost as pH value increased. The differences in
      structural conformation of HPI at different pH values were reflected as better
      foaming capacity at pH 3.0 when compared to pH 5.0, 7.0, and 9.0. At 10 and 25
      mg/mL protein concentrations, emulsions formed by the HPM had smaller oil droplet
      sizes (higher quality), when compared to the HPI-formed emulsions. In contrast at
      50 mg/mL protein concentration, the HPI-formed emulsions had smaller oil droplet
      sizes (except at pH 3.0). We conclude that the functional properties of hemp seed
      protein products are dependent on structural conformations as well as protein
      concentration and pH. 

PMID- 25048775
TI  - Engineering cell-adhesive gellan gum spongy-like hydrogels for regenerative
      medicine purposes.
AB  - The similarity between the extracellular matrix of soft tissue and hydrogels,
      characterized by high-water-content viscoelastic polymeric networks, has been
      sustaining the advancement of hydrogels for tissue engineering and regenerative
      medicine (TERM) purposes. Current research on hydrogels has focused on
      introducing cell-adhesive peptides to promote cell adhesion and spreading, a
      critical applicability limitation. Here we report the development of gellan gum
      (GG) spongy-like hydrogels with ameliorated mechanical performance and
      flexibility in relation to hydrogels, using a simple and cost-effective method.
      Most importantly, these materials allow the entrapment of different cell types
      representing mesenchymal, epidermal and osteoblastic phenotypes that spread
      within the three-dimensional microstructure. This effect was associated with
      microstructural rearrangements characterized by pore wall thickening and pore
      size augmentation, and lower water content than precursor hydrogels. These
      properties significantly affected protein adsorption once cell adhesion was
      inhibited in the absence of serum. Spongy-like hydrogels are not adhesive for
      endothelial cells; however, this issue was surpassed by a pre-incubation with a
      cell-adhesive protein, as demonstrated for other substrates but not for
      traditional hydrogels. The proposed cell-compatible GG-based structures avoid
      time-consuming and expensive strategies that have been used to include cell
      adhesive features in traditional hydrogels. This, associated with their off-the
      shelf availability in an intermediary dried state, represents unique and highly
      relevant features for diverse TERM applications. 

PMID- 25048776
TI  - Catheter-related bloodstream infection in patients with motility disorder of the
      alimentary tract.
AB  - PURPOSE: Catheter-related bloodstream infection (CRBSI) is a serious complication
      associated with parenteral nutrition (PN). We retrospectively examined the
      features of CRBSI in patients with motility disorder (MD) by reviewing medical
      records. METHODS: Patients who received PN for more than 100 days in our hospital
      between January 2009 and September 2013 were reviewed. They were divided into two
      groups based on the presence or absence of MD. The frequency of CRBSI and the
      pathogenic organisms detected were compared. Statistical analysis was performed
      with the Mann-Whitney U test or Fisher's exact test. P < 0.05 was considered
      significant. RESULTS: Six patients had MD (MD group) and four patients had short
      bowels without MD (SB group). The median frequencies of CRBSI were 12.6 per 1,000
      catheter-days in the MD group and 2.3 in the SB group (P = 0.027). The percentage
      of Gram-negative bacilli in all pathogenic organisms was 61% in the MD group and
      22% in the SB group (P = 0.036). CONCLUSION: We found CRBSI was more frequent and
      Gram-negative bacilli were more common in patients with MD. Stasis in the
      alimentary tract and subsequent bacterial overgrowth appear to be risk factors
      for CRBSI. Therefore, it is crucial to seek treatments not to cause intestinal
      stasis.

PMID- 25048777
TI  - A case of congenital diaphragmatic hernia with intradiaphragmatic pulmonary
      sequestration: case report and literature review.
AB  - Extralobar pulmonary sequestration (EPS) can occasionally be found incidentally
      in congenital diaphragmatic hernia (CDH). Extralobar pulmonary sequestration
      usually arises in the chest or the abdomen; rarely in the diaphragm. We report a
      neonatal case of antenatally diagnosed CDH associated with intradiaphragmatic
      EPS. 

PMID- 25048778
TI  - In vivo properties of KNT-127, a novel delta opioid receptor agonist: receptor
      internalization, antihyperalgesia and antidepressant effects in mice.
AB  - BACKGROUND AND PURPOSE: Activation of delta opioid (DOP) receptors regulates pain
      and emotional responses, and also displays ligand-biased agonism. KNT-127
      (1,2,3,4,4a,5,12,12a-octahydro-2-methyl-4abeta,1beta-([1,2]benzenomethano)-2,6
      diazanaphthacene-12abeta,17-diol) is a novel DOP receptor agonist inducing
      analgesia and antidepressant effects in mice. Here, we have assessed KNT-127 for
      (i) analgesia against chronic inflammatory pain; (ii) effects on depression,
      locomotion and DOP receptor internalization; and (iii) for cross-tolerance to
      analgesic and antidepressant effects of acute treatment by other DOP receptor
      agonists. EXPERIMENTAL APPROACH: Inflammatory pain was induced by complete
      Freund's adjuvant injection into tail or hindpaw, and thermal and mechanical
      sensitivities were determined in mice. Locomotor and antidepressant-like effects
      were measured using actimetry and forced swim test respectively. In vivo KNT-127
      selectivity and internalization were assessed using DOP receptor knockout mice
      and knock-in mice expressing fluorescent-tagged DOP receptors. KNT-127 was
      injected acutely at 0.1-10.0 mg.kg(-1) or administered chronically at 5 mg.kg(-1)
      daily over 5 days. KEY RESULTS: Acute treatment with KNT-127 reversed
      inflammatory hyperalgesia, produced an antidepressant-like effect but induced
      neither hyperlocomotion nor receptor sequestration. Chronic treatment with KNT
      127 induced tolerance and cross-tolerance to SNC80-induced analgesia, but no
      tolerance to SNC80-evoked hyperlocomotor or antidepressant-like effects.
      CONCLUSIONS AND IMPLICATIONS: The DOP receptor agonist KNT-127 induced agonist
      specific acute and chronic responses, at both behavioural and cellular levels. It
      displays activities similar to the other recently reported DOP agonists, AR
      M1000390, ADL5747 and ADL5859, and differs from SNC80. SNC80 differs from the
      other DOP receptor agonists including KNT-127, by exhibiting ligand-biased
      tolerance at this receptor.

PMID- 25048779
TI  - Chronic lymphocytic leukemia: moving forward-rapidly.

PMID- 25048780
TI  - The meaning and relevance of B-cell receptor structure and function in chronic
      lymphocytic leukemia.
AB  - The B-cell receptor (BCR) is of critical importance for normal B cells and for
      the majority of B-cell malignancies, especially chronic lymphocytic leukemia
      (CLL). The two major subsets of CLL are biologically distinct, being derived from
      B cells at different stages of differentiation and carrying unmutated (U-CLL) or
      mutated (M-CLL) IGHV genes. U-CLL, which has a poorer prognosis, often has
      relatively conserved (stereotypic) IGHV-HD-HJ sequences, indicative of
      interaction with large (super)antigens and similar to those in normal naive
      innate B cells. Conserved sequences are less evident in M-CLL, in keeping with
      its postfollicular origin. However, both subsets exhibit features of chronic
      antigen exposure in tissue sites, with local proliferative events, but also
      downregulation of surface immunoglobulin M but not surface immunoglobulin D, a
      characteristic of normal anergic B cells. BCR-mediated anergy can spread to other
      receptors such as CXCR4. Circulating CLL cells retain a shadow of tissue-based
      events that can reverse over time, but the overall extent of anergy is greater in
      M-CLL. Despite this stereotypic variety and more genomic complexity, BCR-mediated
      responses in vitro appear relatively homogeneous in U-CLL, but M-CLL is more
      heterogeneous. The differential balance between antigen-induced proliferation or
      anergy is the likely determinant of clinical behavior and possibly of response to
      kinase inhibitors. 

PMID- 25048781
TI  - Microenvironmental interactions in chronic lymphocytic leukemia: the master role
      of CD49d.
AB  - Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease
      characterized by the accumulation/expansion of a clonal population of neoplastic
      cells with the morphologic appearance of small mature B lymphocytes in blood,
      bone marrow, and lymphoid organs. A combination of genetic lesions is primarily
      responsible for the first step(s) of neoplastic transformation, along with
      microenvironmental signals, which concurrently operate by enhancing proliferation
      and/or inhibiting apoptosis. In this context, CD49d is known to play a pivotal
      role in mediating both cell-cell and cell-matrix interactions in CLL-involved
      tissues, eventually delivering pro-survival signals and protecting CLL cells from
      drug-induced damages. In the present review, we address, in detail, CD49d
      activities in the CLL microenvironment, CD49d functional and physical
      interactions with other microenvironmental receptors (including CD38 and B-cell
      receptor), and the relationship of CD49d expression with specific cytogenetic
      features in CLL. 

PMID- 25048783
TI  - Murine genetically engineered and human xenograft models of chronic lymphocytic
      leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a genetically complex disease, with
      multiple factors having an impact on onset, progression, and response to therapy.
      Genetic differences/abnormalities have been found in hematopoietic stem cells
      from patients, as well as in B lymphocytes of individuals with monoclonal B-cell
      lymphocytosis who may develop the disease. Furthermore, after the onset of CLL,
      additional genetic alterations occur over time, often causing disease worsening
      and altering patient outcomes. Therefore, being able to genetically engineer
      mouse models that mimic CLL or at least certain aspects of the disease will help
      us understand disease mechanisms and improve treatments. This notwithstanding,
      because neither the genetic aberrations responsible for leukemogenesis and
      progression nor the promoting factors that support these are likely identical in
      character or influences for all patients, genetically engineered mouse models
      will only completely mimic CLL when all of these factors are precisely defined.
      In addition, multiple genetically engineered models may be required because of
      the heterogeneity in susceptibility genes among patients that can have an effect
      on genetic and environmental characteristics influencing disease development and
      outcome. For these reasons, we review the major murine genetically engineered and
      human xenograft models in use at the present time, aiming to report the
      advantages and disadvantages of each. 

PMID- 25048782
TI  - Evolving understanding of the CLL genome.
AB  - Over the past few years, massively parallel sequencing technologies have revealed
      with high resolution the tremendous genetic and epigenetic heterogeneity in
      chronic lymphocytic leukemia (CLL). We have learned how the molecular
      architecture differs not only between affected individuals but also within
      samples and over time. These insights have catalyzed our understanding of the
      pathobiology of CLL and point to critical signaling pathways in the development
      and progression of the disease. Several key driver alterations have been
      identified, which serve to refine prognostic schemata but also to inspire the
      development of new therapeutic strategies. Ongoing advances in technology promise
      to further elucidate the molecular basis of CLL, and this knowledge is
      anticipated to aid us in understanding and addressing the clinical challenge
      presented by the vast variability in the clinical course of patients with CLL. 

PMID- 25048784
TI  - The B-cell receptor pathway: a critical component of healthy and malignant immune
      biology.
AB  - The pathogenesis and progression of normal B-cell development to malignant
      transformation of chronic lymphocytic leukemia (CLL) is still poorly understood
      and has hampered attempts to develop targeted therapeutics for this disease. The
      dependence of CLL cells on B-cell receptor signaling has fostered a new area of
      basic and therapeutic research interest. In particular, identification of the
      dependence of CLL cells on both phosphatidylinositol 3-kinase delta and Bruton's
      tyrosine kinase signaling for survival and proliferation has come forth through
      well-performed preclinical studies and subsequent trials demonstrating dramatic
      efficacy. This review outlines essential components of B-cell receptor signaling
      and briefly addresses therapeutics that are emerging to target these in patients
      with CLL and related lymphoid malignancies. 

PMID- 25048785
TI  - Targeting BCL2 for the treatment of lymphoid malignancies.
AB  - The failure of apoptosis (programmed cell death) underpins the development of
      many tumors and often renders them resistant to cytotoxic therapies. In
      hematologic malignancies, this impairment of apoptosis is often caused by
      overexpression of the pro-survival protein BCL2. Because abnormally high levels
      of BCL2 sustain these tumors, there has been much interest in targeting BCL2 as a
      novel approach to treating various hematologic malignancies. One such approach is
      the development of BH3 mimetic compounds, small molecules that mimic the action
      of the BH3-only proteins, natural antagonists of BCL2 and its pro-survival
      relatives. These compounds act by restoring the ability of a cell to undergo
      apoptotic cell death. Some of them have shown very encouraging results in early
      phase clinical trials that are currently underway, particularly in patients with
      chronic lymphocytic leukemia and some non-Hodgkin lymphomas, diseases marked by
      BCL2 overexpression. In this review, we discuss the rationale behind targeting
      BCL2, highlight the recent findings from clinical trials, and pinpoint the next
      steps in the clinical development of this interesting and promising class of
      targeted agents, particularly for the treatment of lymphoid malignancies. 

PMID- 25048786
TI  - Immunomodulation and immune reconstitution in chronic lymphocytic leukemia.
AB  - Over the past decade, there have been significant advances in our understanding
      of the pathogenesis of chronic lymphocytic leukemia (CLL), which has been
      accompanied by an explosion in treatment options. Although the combination of
      fludarabine, cyclophosphamide, and rituximab is the current frontline treatment
      of choice for fit patients, targeted therapies such ibrutinib, idelalisib, and
      ABT-199 are showing great promise in clinical trials. However, none of these
      drugs seems curative, and allogeneic hematopoietic stem cell transplantation
      remains the only strategy that produces durable clinical remissions in otherwise
      poor-risk disease. Immune reconstitution remains an enticing prospect in CLL, as
      malignant B cells should be particularly susceptible to a T cell-mediated attack.
      It has recently been demonstrated that the T-cell defect in CLL can be
      effectively overcome by both lenalidomide treatment and by adoptive transfer of
      chimeric antigen receptor T cells. A variety of other immunotherapies are in
      development, including CLL vaccines, CD40 ligand therapies, and monoclonal
      antibody immune checkpoint blockade. This review explores the nature of the
      immune defect in CLL and summarizes the recent developments in the
      immunotherapeutic field. 

PMID- 25048787
TI  - Incorporating targeted agents into future therapy of chronic lymphocytic
      leukemia.
AB  - Treatment of chronic lymphocytic leukemia (CLL) is currently undergoing profound
      changes. Several monoclonal antibodies (ofatumumab and obinutuzumab), and the
      first agent targeting essential signaling cascades in CLL (ibrutinib) have
      recently been approved. Inhibiting the B-cell receptor pathway seems of
      particular importance in effective targeted therapies of CLL. Here, inhibition of
      Bruton's tyrosine kinase and phosphatidylinositol 3-kinase delta currently offer
      the most promising targeted approaches. The clinical course of CLL presents with
      an impressive heterogeneity. During recent years, the combined use of clinical,
      biologic, and genetic parameters has allowed characterization of at least three
      categories of patients(1): (1) patients with a very mild onset and course; (2)
      patients with an intermediate prognosis; and (3) patients with an aggressive
      course of high-risk leukemia. With this background, it becomes increasingly
      challenging to select the right treatment strategy for each patient. In the
      present article, we summarize the current therapeutic tools and their combination
      partner drugs. Moreover, we offer a perspective on how to integrate the novel
      targeted agents for CLL therapy into sequential treatment approaches. 

PMID- 25048788
TI  - Kaledo, a board game for nutrition education of children and adolescents at
      school: cluster randomized controlled trial of healthy lifestyle promotion.
AB  - During childhood and adolescence, a game could be an effective educational tool
      to learn healthy eating habits. We developed Kaledo, a new board game, to promote
      nutrition education and to improve dietary behavior. A two-group design with one
      pre-treatment assessment and two post-treatment assessments was employed. A total
      of 3,110 subjects (9-19 years old) from 20 schools in Campania, Italy, were
      included in the trial. In the treated group, the game was introduced each week
      over 20 consecutive weeks. Control group did not receive any intervention. The
      primary outcomes were (i) score on the "Adolescent Food Habits Checklist" (AFHC),
      (ii) scores on a dietary questionnaire, and (iii) BMI z-score. At the first post
      assessment (6 months), the treated group obtained significantly higher scores
      than the control group on the AFHC (14.4 (95 % confidence interval (CI) 14.0 to
      14.8) vs 10.9 (95 % CI 10.6 to -11.2); F(1,20) = 72.677; p < 0.001) and on four
      sections of the dietary questionnaire: "nutrition knowledge" (6.5 (6.4 to 6.6) vs
      4.6 (4.5 to 4.7); F(1,16) = 78.763; p < 0.001), "healthy and unhealthy diet and
      food" (11.2 (11.0 to 11.4) vs 10.4 (10.3 to 10.6); F(1,32) = 21.324; p < 0.001),
      "food habits" (32.4 (32.0 to 32.8) vs 27.64 (27.3 to 28.0); F(1,26) = 195.039; p
      < 0.001), and "physical activity" (13.4 (13.2 to 13.7) vs 12.0 (11.8 to 12.6);
      F(1,20) = 20.765; p < 0.001). Moreover, the treated group had significantly lower
      BMI z-score with respect to the controls at the first (0.44 (0.42 to 0.46) vs
      0.58 (0.56 to 0.59), F(1,18) = 16.584, p = 0.001) and at the second (18 months)
      (0.34 (0.30 to 0.38) vs 0.58 (0.54 to 0.62), F(1,13) = 7.577; p = 0.017) post
      assessments. CONCLUSION: Kaledo improved nutrition knowledge and dietary behavior
      over 6 months and had a sustained effect on the BMI z-score. Therefore, it may be
      used as an effective tool in childhood and adolescence obesity prevention
      programs.

PMID- 25048789
TI  - No evidence to support a priming strategy with FFP in infants.

PMID- 25048790
TI  - Low levels of 3,3'-diindolylmethane activate estrogen receptor alpha and induce
      proliferation of breast cancer cells in the absence of estradiol.
AB  - BACKGROUND: 3,3'-diindolylmethane (DIM) is an acid-catalyzed dimer of idole-3
      carbinol (I3C), a phytochemical found in cruciferous vegetables that include
      broccoli, Brussels sprouts and cabbage. DIM is an aryl hydrocarbon receptor (AhR)
      ligand and a potential anticancer agent, namely for the treatment of breast
      cancer. It is also advertised as a compound that regulates sex hormone
      homeostasis. METHODS: Here we make use of RNA expression assays coupled to
      Chromatin Immunoprecipitation (ChIP) in breast cancer cell lines to study the
      effect of DIM on estrogen signaling. We further make use of growth assays, as
      well as fluorescence-activated cell sorting (FACS) assays, to monitor cell
      growth. RESULTS: In this study, we report that 'physiologically obtainable'
      concentrations of DIM (10 MUM) activate the estrogen receptor alpha (ERalpha)
      signaling pathway in the human breast cancer cell lines MCF7 and T47D, in a
      17beta-estradiol (E2)-independent manner. Accordingly, we observe induction of
      ERalpha target genes such as GREB1 and TFF1, and an increase in cellular
      proliferation after treatment with 10 MUM DIM in the absence of E2. By using an
      ERalpha specific inhibitor (ICI 182 780), we confirm that the transcriptional and
      proliferative effects of DIM treatment are mediated by ERalpha. We further show
      that the protein kinase A signaling pathway participates in DIM-mediated
      activation of ERalpha. In contrast, higher concentrations of DIM (e.g. 50 MUM)
      have an opposite and expected effect on cells, which is to inhibit proliferation.
      CONCLUSIONS: We document an unexpected effect of DIM on cell proliferation, which
      is to stimulate growth by inducing the ERalpha signaling pathway. Importantly,
      this proliferative effect of DIM happens with potentially physiological
      concentrations that can be provided by the diet or by taking caplet supplements.

PMID- 25048791
TI  - Association of reduced type IX collagen gene expression in human osteoarthritic
      chondrocytes with epigenetic silencing by DNA hypermethylation.
AB  - OBJECTIVE: To investigate whether the changes in collagen gene expression in
      osteoarthritic (OA) human chondrocytes are associated with changes in the DNA
      methylation status in the COL2A1 enhancer and COL9A1 promoter. METHODS:
      Expression levels were determined using quantitative reverse transcription
      polymerase chain reaction, and the percentage of DNA methylation was quantified
      by pyrosequencing. The effect of CpG methylation on COL9A1 promoter activity was
      determined using a CpG-free vector; cotransfections with expression vectors
      encoding SOX9, hypoxia-inducible factor 1alpha (HIF-1alpha), and HIF-2alpha were
      carried out to analyze COL9A1 promoter activities in response to changes in the
      methylation status. Chromatin immunoprecipitation assays were carried out to
      validate SOX9 binding to the COL9A1 promoter and the influence of DNA
      methylation. RESULTS: Although COL2A1 messenger RNA (mRNA) levels in OA
      chondrocytes were 19-fold higher than those in the controls, all of the CpG sites
      in the COL2A1 enhancer were totally demethylated in both samples. The levels of
      COL9A1 mRNA in OA chondrocytes were 6,000-fold lower than those in controls; 6
      CpG sites of the COL9A1 promoter were significantly hypermethylated in OA
      patients as compared with controls. Treatment with 5-azadeoxycitidine enhanced
      COL9A1 gene expression and prevented culture-induced hypermethylation. In vitro
      methylation decreased COL9A1 promoter activity. Mutations in the 5 CpG sites
      proximal to the transcription start site decreased COL9A1 promoter activity.
      Cotransfection with SOX9 enhanced COL9A1 promoter activity; CpG methylation
      attenuated SOX9 binding to the COL9A1 promoter. CONCLUSION: This first
      demonstration that hypermethylation is associated with down-regulation of COL9A1
      expression in OA cartilage highlights the pivotal role of epigenetics in OA,
      involving not only hypomethylation, but also hypermethylation, with important
      therapeutic implications for OA treatment.

PMID- 25048792
TI  - Objectively measured physical activity has a negative but weak association with
      academic performance in children and adolescents.
AB  - AIM: There is an emerging body of evidence on the potential effects of regular
      physical activity on academic performance. The aim of this study was to add to
      the debate, by examining the association between objectively measured physical
      activity and academic performance in a relatively large sample of children and
      adolescents. METHODS: The Spanish UP & DOWN study is a 3-year longitudinal study
      designed to assess the impact, overtime, of physical activity and sedentary
      behaviours on health indicators. This present analysis was conducted with 1778
      children and adolescents aged 6-18 years. Physical activity was objectively
      measured by accelerometry. Academic performance was assessed using school grades.
      RESULTS: Physical activity was inversely associated with all academic performance
      indicators after adjustment for potential confounders, including neonatal
      variables, fatness and fitness (all p < 0.05). This association became
      nonsignificant among quartiles of physical activity. There were only slight
      differences in academic performance between the lowest and the second quartile of
      physical activity, compared to the highest quartile, with very small effect size
      (d < 0.20). CONCLUSION: Objectively measured physical activity may influence
      academic performance during both childhood and adolescence, but this association
      was negative and very weak. Longitudinal and intervention studies are necessary
      to further our understanding.

PMID- 25048793
TI  - Dispersive liquid-liquid microextraction combined with non-aqueous capillary
      electrophoresis for the determination of imazalil, prochloraz and thiabendazole
      in apples, cherry tomatoes and grape juice.
AB  - BACKGROUND: Fruit and vegetables are frequently treated with fungicides to reduce
      possible spoilage. As a result, fungicide residues may be accumulated in derived
      products. This important group of chemical compounds has been heavily regulated
      because of their potential toxicity. Therefore, a simple and rapid method to
      determine fungicides is desired. RESULTS: A simple non-aqueous capillary
      electrophoresis (NACE) method based on dispersive liquid-liquid microextraction
      (DLLME) has been proposed for the determination of imazalil, prochloraz and
      thiabendazole fungicides in fruits and juice samples. Separation buffer consisted
      of a methanol-acetonitrile mixture (35:65, v/v) containing 30 mmol L-1 ammonium
      chloride and 0.5% phosphoric acid. The optimum DLLME conditions were 80 uL
      trichloromethane as extraction solvent, 0.5 mL tetrahydrofuran as disperser
      solvent, sample solution pH at 6.0, 5% (w/v) NaCl and 10 s extraction time.
      Recoveries obtained for various samples ranged from 72% to 102%, with relative
      standard deviation lower than 6.4%. The limits of detection ranged from 0.47 to
      0.72 ug kg-1. CONCLUSION: The proposed method takes the advantages of DLLME and
      NACE. It is rapid, accurate, sensitive and reproducible for the determination of
      imazalil, prochloraz and thiabendazole in fruit samples.

PMID- 25048794
TI  - Impact of medication reconciliation and review on clinical outcomes.
AB  - OBJECTIVE: To examine the evidence regarding the effectiveness of medication
      reconciliation and review and to improve clinical outcomes in hospitals, the
      community, and aged care facilities. DATA SOURCE: This systematic review was
      undertaken in concordance with the PRISMA statement. Electronic databases,
      including MEDLINE, PsycINFO, EMBASE, and CINAHL were searched for relevant
      articles published between January 2000 and March 2014. STUDY SELECTION AND DATA
      EXTRACTION: Randomized and nonrandomized studies rating the severity of
      medication discrepancies and medication-related problems identified during
      medication reconciliation and/or review were considered for inclusion. Data were
      extracted independently by 2 authors using a data collection form. DATA
      SYNTHESIS: Of the 5292 articles identified, 83 articles met the inclusion
      criteria. Medication reconciliation identified unintentional medication
      discrepancies in 3.4% to 98.2% of patients. There is limited evidence of the
      potential of these discrepancies to cause harm. Medication reviews identified
      medication-related problems or possible adverse drug reactions in 17.2% to 94.0%
      of patients. The studies reported conflicting findings regarding the impact of
      medication review on length of stays, readmissions, and mortality. CONCLUSIONS:
      The evidence demonstrates that medication reconciliation has the potential to
      identify many medication discrepancies and reduce potential harm, but the impact
      on clinical outcomes is less clear. Similarly, medication review can detect
      medication-related problems in many patients, but evidence of clinical impact is
      scant. Overall, there is limited evidence that medication reconciliation and
      medication review processes, as currently performed, significantly improve
      clinical outcomes, such as reductions in hospital readmissions.

PMID- 25048795
TI  - A spatial analysis to study access to emergency obstetric transport services
      under the public private "Janani Express Yojana" program in two districts of
      Madhya Pradesh, India.
AB  - BACKGROUND: The government in Madhya Pradesh (MP), India in 2006, launched
      "Janani Express Yojana" (JE), a decentralized, 24X7, free emergency transport
      service for all pregnant women under a public-private partnership. JE supports
      India's large conditional cash transfer program, the "Janani Suraksha Yojana"
      (JSY) in the province and transports on average 60,000 parturients to hospital
      every month. The model is a relatively low cost one that potentially could be
      adopted in other parts of India and South Asia. This paper describes the uptake,
      time taken and geographic equity in access to the service to transport women to a
      facility in two districts of MP. METHODS: This was a facility based cross
      sectional study. We interviewed parturients (n = 468) who delivered during a five
      day study period at facilities with >10 deliveries/month (n = 61) in two study
      districts. The women were asked details of transportation used to arrive at the
      facility, time taken and their residential addresses. These details were plotted
      onto a Geographic Information System (GIS) to estimate travelled distances and
      identify statistically significant clusters of mothers (hot spots) reporting
      delays >2 hours. RESULTS: JE vehicles were well dispersed across the districts
      and used by 236 (50.03%) mothers of which 111(47.03%) took >2 hours to reach a
      facility. Inability of JE vehicle to reach a mother in time was the main reason
      for delays. There was no correlation between the duration of delay and distance
      travelled. Maps of the travel paths and travel duration of the women are
      presented. The study identified hot spots of mothers with delays >2 hours and
      explored the possible reasons for longer delays. CONCLUSIONS: The JE service was
      accessible in all parts of the districts. Relatively high utilization rates of JE
      indicate that it ably supported JSY program to draw more women for institutional
      deliveries. However, half of the JE users experienced long (>2 hour) delays. The
      delayed mothers clustered in difficult terrains of the districts. Additional
      support particularly for the identified hot spots, enhanced monitoring by state
      agencies and GIS tools can facilitate better effectiveness of the JE program.

PMID- 25048797
TI  - Biofabrication of tissue constructs by 3D bioprinting of cell-laden
      microcarriers.
AB  - Bioprinting allows the fabrication of living constructs with custom-made
      architectures by spatially controlled deposition of multiple bioinks. This is
      important for the generation of tissue, such as osteochondral tissue, which
      displays a zonal composition in the cartilage domain supported by the underlying
      subchondral bone. Challenges in fabricating functional grafts of clinically
      relevant size include the incorporation of cues to guide specific cell
      differentiation and the generation of sufficient cells, which is hard to obtain
      with conventional cell culture techniques. A novel strategy to address these
      demands is to combine bioprinting with microcarrier technology. This technology
      allows for the extensive expansion of cells, while they form multi-cellular
      aggregates, and their phenotype can be controlled. In this work, living
      constructs were fabricated via bioprinting of cell-laden microcarriers.
      Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via
      static culture or spinner flask expansion, were encapsulated in gelatin
      methacrylamide-gellan gum bioinks, and the printability of the composite material
      was studied. This bioprinting approach allowed for the fabrication of constructs
      with high cell concentration and viability. Microcarrier encapsulation improved
      the compressive modulus of the hydrogel constructs, facilitated cell adhesion,
      and supported osteogenic differentiation and bone matrix deposition by MSCs.
      Bilayered osteochondral models were fabricated using microcarrier-laden bioink
      for the bone compartment. These findings underscore the potential of this new
      microcarrier-based biofabrication approach for bone and osteochondral constructs.

PMID- 25048798
TI  - Association of increased circulating catecholamine and glucocorticoid levels with
      risk of psychological problems in oral neoplasm patients.
AB  - BACKGROUND: Noradrenergic pathways and glucocorticoid-mediated signal pathways
      have been implicated in the growth and progression of oral cancer. Patients with
      oral neoplasms can have high psychological distress levels, but the effects of
      stress-related hormones on oral neoplasm growth are unknown. METHODS: We have
      investigated the relationships between pre-surgical measurements of psychological
      problems with Symptom Checklist-90-revised Inventory (SCL90-R), tumor histology,
      circulating blood catecholamine and glucocorticoid levels among 75 oral neoplasm
      patients, including 40 oral cancer patients and 35 benign oral tumor patients.
      RESULTS: The results showed that most dimension scores of SCL90-R did not show a
      significant difference between the two groups except depression (p = 0.0201) and
      obsessive-compulsion (p = 0.0093), with the scores for these symptoms being
      higher among oral cancer group versus the benign oral tumor group. The
      differences of total score, average score and other monomial factor scores were
      not statistically significant. The mean concentrations of catecholamine and
      glucocorticoid in peripheral blood of the oral cancer group were higher than
      those in benign oral tumor group (p<0.01). We also examined whether associations
      observed between biobehavioral measures and circulating blood catecholamine and
      glucocorticoid levels extended to other compartments in the oral cancer group.
      CONCLUSIONS: These findings suggest that stress hormones may affect oral cancer
      behavior by influencing the tumor micro-environment though the circulating blood.

PMID- 25048799
TI  - A comparison of tablet computer and paper-based questionnaires in healthy aging
      research.
AB  - BACKGROUND: Digital questionnaire delivery offers many advantages to
      investigators and participants alike; however, evidence supporting digital
      questionnaire delivery via touchscreen device in the older adult population is
      lacking. OBJECTIVE: The objective of this study was to compare the use of tablet
      computer-delivered and printed questionnaires as vehicles for the collection of
      psychosocial data from older adults to determine whether this digital platform
      would be readily adopted by the sample, and to identify whether tablet delivery
      influences the content of data received. METHODS: The participants completed
      three questionnaires using both delivery methods, followed by a brief evaluation.
      RESULTS: A nonparametric one-sample binomial test indicated a significantly
      greater proportion of individuals preferred the tablet-delivered questionnaires
      (z=4.96, SE 3.428, P<.001). Paired sample t tests and Wilcoxon sign-rank tests
      indicated that measures collected by each method were not significantly different
      (all P>=.273). Ease of use of the tablet interface and anxiety while completing
      the digital questionnaires were significantly correlated with preferences,
      (rs=.665, P<.001 and rs=.552, P<.001, respectively). Participants most frequently
      reported that the tablet delivery increased speed of use and improved data entry,
      although navigation was perceived as being more difficult. By comparison,
      participants felt that the paper packet was easier to read and navigate, but was
      slow and cumbersome, and they disliked the lack of dynamic features. CONCLUSIONS:
      This study provides preliminary evidence suggesting that questionnaires delivered
      to older adults using contemporary tablet computers may be acceptable and do not
      substantively influence the content of the collected data.

PMID- 25048800
TI  - Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to
      epigenetic modifications and impaired systemic immunity in T cells.
AB  - BACKGROUND: Evidence suggests that exposure to polycyclic aromatic hydrocarbons
      (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased
      severity of atopic diseases. OBJECTIVE: We hypothesized that ambient PAH exposure
      is linked to impairment of immunity in atopic children (defined as children with
      asthma and/or allergic rhinitis) from Fresno, California, an area with elevated
      ambient PAHs. METHODS: We recruited 256 subjects from Fresno, CA. Ambient PAH
      concentrations (ng/m(3) ) were measured using a spatial-temporal regression model
      over multiple time periods. Asthma diagnosis was determined by current NHLBI
      criteria. Phenotyping and functional immune measurements were performed from
      isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced.
      RESULTS: We show that higher average PAH exposure was significantly associated
      with impaired Treg function and increased methylation in the forkhead box protein
      3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic
      modifications were significantly linked to differential protein expression of
      FOXP3 (P < 0.001). Methylation was associated with cellular functional changes,
      specifically Treg dysfunction, and an increase in total plasma IgE levels.
      Protein expression of IL-10 decreased and IFN-gamma increased as the extent of
      PAH exposure increased. The strength of the associations generally increased as
      the time window for average PAH exposure increased from 24 hr to 1 year,
      suggesting more of a chronic response. Significant associations with chronic PAH
      exposure and immune outcomes were also observed in subjects with allergic
      rhinitis. CONCLUSIONS AND CLINICAL RELEVANCE: Collectively, these results
      demonstrate that increased ambient PAH exposure is associated with impaired
      systemic immunity and epigenetic modifications in a key locus involved in atopy:
      FOXP3, with a higher impact on atopic children. The results suggest that
      increased atopic clinical symptoms in children could be linked to increased PAH
      exposure in air pollution.

PMID- 25048801
TI  - Nutrition assessment and risk prediction in dialysis patients-a new integrative
      score.
AB  - OBJECTIVE: We developed a quantitative nutritional score, based on biochemical
      measures, taken as part of monthly routine care. The score can be accomplished
      within a short time after routine laboratory results completion and identify a
      monthly change in nutritional status. DESIGN: A longitudinal observational cohort
      study SETTING: The Institute of Nephrology, Wolfson Medical Center, Holon,
      Israel. SUBJECTS: A total of 179 hemodialysis patients were followed up for up to
      2.5 years after study baseline. INTERVENTION: The Integrative Clinical Nutrition
      Dialysis Score (ICNDS) is based on the biochemical measures of albumin,
      creatinine, urea, cholesterol, C-reactive protein, dialysis adequacy, and weight
      change. Each parameter is ranked between 1 and 5, with the higher rank derived
      from recommended National Kidney Foundation Kidney Disease/Dialysis Outcomes and
      Quality Initiative values and the lower rank indicating deviation from those
      values. The final ICNDS is the sum of ranks over 7 parameters. MAIN OUTCOME
      MEASURE: The Pearson correlation coefficient was calculated for association
      between subjective global assessment and ICNDS in 63 randomly selected patients.
      In 179 dialysis patients, the baseline ICNDS, the slope of 3 subsequent monthly
      ICNDS values, were tested for their correlation with odds of all-cause mortality,
      hospitalization frequency, length of stay, after 31 months. Spline Cox regression
      was used to select the best cutoff point, associated with severe mortality risk.
      RESULTS: Score results were significantly correlated with nutrition evaluation by
      subjective global assessment (r = 0.842, P < .01). For a unit increase in
      baseline score, death odds were significantly decreased (hazard ratio [HR] =
      0.929, 95% confidence interval [CI] 0.88-0.974, P < .002). Each unit increase in
      slope significantly reduced mortality risk (HR = 0.485, 95% CI 0.278-0.847, P <
      .011). Hospitalization frequency was significantly increased across worsening
      baseline score (HR = 0.935, 95% CI 0.906-0.964, P < .0001). A 1-unit increase in
      slope significantly decreased hospitalization (HR = 0.799, 95% CI 0.726-0.881, P
      < .0001). CONCLUSIONS: Results confirm that ICNDS is a useful prognostic tool
      that serves to detect nutrition deterioration at its very beginning.

PMID- 25048804
TI  - From double-four-ring germanosilicates to new zeolites: in silico investigation.
AB  - To date, the majority of zeolites have been prepared by the solvothermal route
      using organic structure directing agents. Two new zeolites with structural codes
      PCR and OKO were recently prepared from UTL germanosilicate by removal of the
      double-four ring (D4R) connecting the dense two-dimensional layers [Nature Chem.
      2013, 5, 628]. The corresponding experimental protocol, Assembly-Disassembly
      Organization-Reassembly (ADOR), is explored in this contribution with an in
      silico investigation. The structure and properties of hypothetical zeolites that
      could be obtained from zeolites with IWW, IWV, IWR, ITR, and ITH topologies using
      the ADOR protocol are reported based on a computational investigation. A total of
      20 new structures are presented together with their characteristics. 

PMID- 25048802
TI  - A subset of circulating blood mycobacteria-specific CD4 T cells can predict the
      time to Mycobacterium tuberculosis sputum culture conversion.
AB  - We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)-
      and PPD-specific CD4 T cell responses and followed them over 6 months of drug
      therapy. Twelve of these patients were sputum culture (SC) positive and six
      patients were SC negative upon enrollment. Our aim was to identify a subset of
      mycobacteria-specific CD4 T cells that would predict time to culture conversion.
      The total frequency of mycobacteria-specific CD4 T cells at baseline could not
      distinguish patients showing positive or negative SC. However, a greater
      proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells
      was found in SC positive patients than in those who were SC negative (p = 0.004
      and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR+ Ki67+
      on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC
      positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver
      operating characteristic (ROC) analysis revealed that baseline levels of Ki67+
      HLA-DR+ Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum
      culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment,
      there was a significant decline of these Ki67+ HLA-DR+ T cell populations in the
      first 2 months, with a progressive increase in mycobacteria-specific
      polyfunctional IFNgamma+ IL2+ TNFalpha+ CD4 T cells over 6 months. Thus, a subset
      of activated and proliferating mycobacterial-specific CD4 T cells (Ki67+ HLA-DR+)
      may provide a valuable marker in peripheral blood that predicts time to sputum
      culture conversion in TB patients at the start of treatment.

PMID- 25048805
TI  - Giant dielectric and magnetoelectric responses in insulating nanogranular films
      at room temperature.
AB  - The electric and magnetic properties of matter are of great interest for
      materials science and their use in electronic applications. Large dielectric and
      magnetoelectric responses of materials at room temperature are a great advantage
      for electromagnetic device applications. Here we present a study of FeCo-MgF
      nanogranular films exhibiting giant dielectric and magnetoelectric responses at
      room temperature; with dielectric constant epsilon'=490 and magnetoelectric
      response Deltaepsilon'/epsilon'0=3%. In these films, Fe-Co alloy-based nanometer
      sized magnetic granules are dispersed in a Mg-fluoride-based insulator matrix.
      Insulating nanogranular films are a new class of multifunctional materials. The
      giant responses are caused by spin-dependent charge oscillation between magnetic
      granules via quantum-mechanical tunnelling. A possible application of such
      insulating nanogranular materials with giant response is in the construction of a
      tunable device, in which impedance components such as capacitance and inductance
      are tunable at room temperature. 

PMID- 25048806
TI  - Rutin alleviates prion peptide-induced cell death through inhibiting apoptotic
      pathway activation in dopaminergic neuronal cells.
AB  - Prion disorders are progressive neurodegenerative diseases characterized by
      extensive neuronal loss and accumulation of the abnormal form of the scrapie
      prion protein (PrP). Rutin is a flavonoid that occurs naturally in plant-derived
      beverages and foods and is used in traditional and folkloric medicine worldwide.
      In the present study, we evaluated the protective effects of rutin against PrP
      fragment (106-126)-induced neuronal cell death. Rutin treatment blocked PrP (106
      126)-mediated increases in reactive oxygen species production and nitric oxide
      release and helped slowing the decrease of neurotrophic factors that results from
      PrP accumulation. Rutin attenuated PrP (106-126)-associated mitochondrial
      apoptotic events by inhibiting mitochondrial permeability transition and caspase
      3 activity and blocking expression of the apoptotic signals Bax and PARP.
      Additionally, rutin treatment significantly decreased the expression of the death
      receptor Fas and its ligand Fas-L. Overall, our results demonstrated that rutin
      protects against the neurodegenerative effects of prion accumulation by
      increasing production of neurotropic factors and inhibiting apoptotic pathway
      activation in neuronal cells. These results suggested that rutin may have
      clinical benefits for prion diseases and other neurodegenerative disorders.

PMID- 25048807
TI  - Conservative therapy as a primary treatment for spontaneous isolated dissection
      of the superior mesenteric artery.
AB  - BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery
      (SIDSMA) is a rare and potentially fatal disease. Several therapeutic options are
      available, including conservative therapy, endovascular repair, and open surgery.
      Herein, we report our experiences in the treatment of SIDSMA. METHODS: Between
      February 2009 and June 2013, 17 patients were diagnosed as having SIDSMA. We
      retrospectively reviewed and analyzed their clinical characteristics, medical
      history, risk factors, symptoms, diagnostic imaging modality, treatment, and
      outcome. The lesions were categorized according to the modified Sakamoto's
      classification. If no evidence of bowel necrosis or arterial rupture was present
      in the patients with symptomatic SIDSMA, we first performed conservative therapy,
      even if the patients had abdominal pain. RESULTS: The subjects included 15 men
      and 2 women, with a median age of 62.8 years. Eight patients were symptomatic and
      9 were asymptomatic. Conservative therapy included the use of antithrombotic
      agents in 3 patients but not in 5 patients. During the follow-up period (mean,
      21.1 months), all the patients were discharged without any significant
      complications, and none of the patients showed the progression of the dissection
      on follow-up computed tomography angiography examinations. CONCLUSIONS:
      Conservative therapy without antithrombotic agents should be the primary
      treatment for SIDSMA. Endovascular repair for SIDSMA is associated with several
      risks, thus the procedure might occasionally be useful and necessary.

PMID- 25048808
TI  - Computed tomography and magnetic resonance imaging of the coronary sinus:
      anatomic variants and congenital anomalies.
AB  - The coronary sinus (CS) is an important vascular structure that allows for access
      into the coronary veins in multiple interventional cardiology procedures,
      including catheter ablation of arrhythmias, pacemaker implantation and retrograde
      cardioplegia. The success of these procedures is facilitated by the knowledge of
      the CS anatomy, in particular the recognition of its variants and anomalies. This
      pictorial essay reviews the spectrum of CS anomalies, with particular attention
      to the distinction between clinically benign variants and life-threatening
      defects. Emphasis will be placed on the important role of cardiac CT and
      cardiovascular magnetic resonance in providing detailed anatomic and functional
      information of the CS and its relationship to surrounding cardiac structures.
      Teaching Points * Cardiac CT and cardiovascular magnetic resonance offer 3D high
      resolution mapping of the coronary sinus in pre-surgical planning.* Congenital
      coronary sinus enlargement occurs in the presence or absence of a left-to-right
      shunt.* Lack of recognition of coronary sinus anomalies can lead to adverse
      outcomes in cardiac procedures.* In coronary sinus ostial atresia, coronary
      venous drainage to the atria occurs via Thebesian or septal veins.* Coronary
      sinus diverticulum is a congenital outpouching of the coronary sinus and may
      predispose to cardiac arrhythmias. 

PMID- 25048809
TI  - [Reliability and validity of the 3 Dimensional Sleep Scale (3DSS)--day workers
      version--in assessing sleep phase, quality, and quantity].
AB  - OBJECTIVES: Most sleep scales assess sleep quantity (e.g., sleep duration and
      daytime sleepiness) or sleep quality (e.g., sleep latency and maintenance); the
      Pittsburgh Sleep Quality Index (PSQI) is an exceptional example. However, the
      prevalence of 24-hour operations presents the need for a scale that can also
      measure sleep phase (e.g., sleep onset and offset). Furthermore, we have to
      assess the phase, quality and quantity respectively to understand which of them
      has a problem. Thus, the 3 Dimensional Sleep Scale (3DSS) - day workers version -
      was developed to assess each of them related to sleep, and this study attempted
      to verify its reliability and validity. METHODS: Subjects were 635 day workers
      (461 men, 174 women; average age = 40.5 years) from the manufacturing and service
      industries. A scale was created based on a pre-study and discussions with
      specialists. The scale consisted of 17 sleep-related items. The skew of the data
      was assessed, and the construct validity and reliability were verified using
      exploratory and confirmatory factor analysis and Cronbach's alpha, respectively.
      The scale was scored and G-P analysis was performed. The items measuring phase,
      quality, and quantity of sleep were selected from the PSQI and SDS, and their
      correlation with the three scales of 3DSS were measured to verify the convergent
      and discriminant validity. In addition, the total scores obtained on the PSQI
      were compared with each scale of the 3DSS. RESULTS: No skew was found in the
      data. Exploratory factor analysis revealed a three-factor structure--quality,
      quantity, and phase. Each factor consisted of five items, therefore two items
      were excluded. The fitness of the 15-item model was better than that of the 17
      item model according to confirmatory factor analysis. Cronbach's alpha for phase,
      quality and quantity score were 0.685, 0.768 and 0.716, respectively. The
      hypothesis tests were almost accepted, therefore convergent and discriminant
      validity were sufficiently established. CONCLUSIONS: The present study
      established the reliability and validity of the 3DSS; however, further studies
      using larger samples are needed to standardize the test and to establish a cut
      off value.

PMID- 25048810
TI  - [Impact of visceral fat measurements and a weight loss support web system on
      visceral fat loss in a workplace setting: insights from a JVALUE2 (Japanese study
      of visceral adiposity and lifestyle information; utilization and evaluation)].
AB  - OBJECTIVES: Providing different programs of occupational health services in the
      same company is difficult. We report the results of a parallel randomized trial
      for the employees of our company for visceral fat measurements and the effect of
      a weight loss support web system. MATERIALS AND METHODS: 181 healthy employees
      with BMI over 23 who volunteered to participate in this study. In a parallel
      randomized study, we divided them into 3 groups (A, health guidance by
      occupational health staff with visceral fat measurements and a weight loss
      support web system; B, health guidance by occupational health staff with a weight
      loss support web system; C, without health guidance (control)) by date of birth.
      To assess the effects of guidance and support, we compared each group's waist
      circumference (WC), weight, and BMI, before and after the guidance. We also
      conducted questionnaire surveys of eating behavior and life activities before and
      after the guidance to estimate the relationship between the intervention method
      used for each group and their behavioral modification. RESULTS: 150 employees
      (83%) finished this program. Within 3 months, reduction in the outcome measures
      was largest in group A, and showed significant differences from the other two
      groups. For many employees in group A, eating behavior factors improved markedly;
      however, in the control group, there were no changes in eating behavior or daily
      living activities. CONCLUSIONS: A parallel randomized trial involving the
      employees of our company was performed and we scientifically verified the effects
      of an occupational health programs. Objective study of occupational health
      activities and measures were enabled by devising methods and procedures, e.g.,
      applying the waiting-list method for the control group. This approach will lead
      to appropriate selection and precise implementation of evidence-based measures in
      occupational health in the future.

PMID- 25048811
TI  - Design, synthesis, antibacterial evaluation and docking study of novel 2-hydroxy
      3-(nitroimidazolyl)-propyl-derived quinolone.
AB  - A novel series of 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolones 6a-o
      were synthesized and evaluated for their in vitro antibacterial activity. Most of
      the target compounds exhibited potent activity against Gram-positive strains.
      Among them, moxifloxacin analog 6n displayed the most potent activity against
      Gram-positive strains including S. epidermidis (MIC = 0.06 MUg/mL), MSSE (MIC =
      0.125 MUg/mL), MRSE (MIC = 0.03 MUg/mL), S. aureus (MIC = 0.125 MUg/mL), MSSA
      (MIC = 0.125 MUg/mL), (MIC = 2 MUg/mL). Its activity against MRSA was eightfold
      more potent than reference drug gatifloxacin. Finally, docking study of the
      target compound 6n revealed that the binding model of quinolone nucleus was
      similar to that of gatifloxacin and the 2-hydroxy-3-(nitroimidazolyl)-propyl
      group formed two additional hydrogen bonds.

PMID- 25048812
TI  - Aurora kinases as druggable targets in pediatric leukemia: heterogeneity in
      target modulation activities and cytotoxicity by diverse novel therapeutic
      agents.
AB  - Leukemia is the most common pediatric malignancy, constituting more than 30% of
      all childhood cancers. Although cure rates have improved greatly, approximately
      one in five children relapse and poor survival rates post relapse remain a
      challenge. Given this, more effective and innovative therapeutic strategies are
      needed in order to improve prognosis. Aurora kinases, a family of
      serine/threonine kinases essential for the regulation of several mitotic
      processes, have been identified as potential targets for cancer therapeutics.
      Elevated expression of Aurora kinases has been demonstrated in several
      malignancies and is associated with aberrant mitotic activity, aneuploidy and
      alterations in chromosomal structure and genome instability. Based on this
      rationale, a number of small molecule inhibitors have been formulated and
      advanced to human studies in the recent past. A comparative analysis of these
      agents in cytotoxicity and target modulation analyses against a panel of leukemia
      cells provides novel insights into the unique mechanisms and codependent activity
      pathways involved in targeting Aurora kinases, constituting a distinctive
      preclinical experimental framework to identify appropriate agents and
      combinations in future clinical studies. 

PMID- 25048813
TI  - Exploring responses to art in adolescence: a behavioral and eye-tracking study.
AB  - Adolescence is a peculiar age mainly characterized by physical and psychological
      changes that may affect the perception of one's own and others' body. This
      perceptual peculiarity may influence the way in which bottom-up and top-down
      processes interact and, consequently, the perception and evaluation of art. This
      study is aimed at investigating, by means of the eye-tracking technique, the
      visual explorative behavior of adolescents while looking at paintings. Sixteen
      color paintings, categorized as dynamic and static, were presented to twenty
      adolescents; half of the images represented natural environments and half human
      individuals; all stimuli were displayed under aesthetic and movement judgment
      tasks. Participants' ratings revealed that, generally, nature images are
      explicitly evaluated as more appealing than human images. Eye movement data, on
      the other hand, showed that the human body exerts a strong power in orienting and
      attracting visual attention and that, in adolescence, it plays a fundamental role
      during aesthetic experience. In particular, adolescents seem to approach human
      content images by giving priority to elements calling forth movement and action,
      supporting the embodiment theory of aesthetic perception. 

PMID- 25048814
TI  - Substance over style: is there something wrong with abandoning the white coat?
AB  - In this paper, we address points raised by Stephanie Dancer's article in The BMJ
      in which she claimed that by 'dressing down', physicians fail to adhere to the
      dignitas of the medical profession, and damage its reputation. At the beginning
      of this paper, we distinguish between two different senses in which a person can
      be, as she terms it, 'scruffy'; and then we address Dancer's three main claims.
      First, we argue that in regard to the medical profession it is fallacious to
      assume, as she appears to do, that someone is incompetent or irresponsible when
      such a judgement is grounded in the fact that a physician is not dressed in a
      formal way. Second, we argue, contrary to her claim, that the dignified nature of
      the medical profession is in no coherent way linked to sartorial elegance or lack
      thereof, but rather, that such dignity is bound to the value of the medical
      practice in itself, to patients, and to society at large. Third, we examine two
      ways in which doctors can 'dress down' and show that 'scruffiness' does not
      necessarily intimates a lack of personal hygiene. Finally, we show that pointing
      to mere statistical correlation without causation, cannot be used as an argument
      against scruffiness. We conclude by suggesting that in the medical context, it is
      more appropriate to educate patients than to chastise practitioners for not
      following arbitrary cultural mores.

PMID- 25048815
TI  - Reply: To PMID 21858175.

PMID- 25048816
TI  - Pd-catalysed mono- and dicarbonylation of aryl iodides: insights into the
      mechanism and the selectivity.
AB  - The mechanism of the experimentally reported phosphine-free palladium-catalysed
      carbonylation of aryl iodides with amines in the presence of 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) as base was investigated at the DFT level.
      Paths were identified for both di- and monocarbonylation, and the calculated
      selectivity for three different substrates was in agreement with experiment. In
      dicarbonylation yielding alpha-ketoamides, formation of the second carbon-carbon
      bond occurs through reductive elimination in the Pd acyl amide intermediate after
      DBU-assisted nucleophilic attack of an amine at a terminal CO ligand. This path
      yields the major product with iodobenzene and the almost exclusive product with p
      methoxyiodobenzene. Two different possible pathways yield the monocarbonylated
      amide product. In one of them, which affords the minor product for iodobenzene,
      base-assisted nucleophilic attack of the amine takes place on a Pd-bound acyl
      ligand. For substrates with electron-withdrawing substituents, such as p
      cyanoiodobenzene, aryl migration to the CO ligand is disfavoured, and this allows
      base-assisted amine attack at a terminal CO ligand early in the catalytic cycle.
      From the resulting Pd amide aryl complex, the subsequent reductive elimination
      occurs easily, and monocarbonylation becomes favoured. 

PMID- 25048818
TI  - Flexible visible-light photodetectors with broad photoresponse based on ZrS3
      nanobelt films.
AB  - Two new flexible visible-light photodetectors based on ZrS3 nanobelts films are
      fabricated on a polypropylene (PP) film and printing paper, respectively, by an
      adhesive-tape transfer method, and their light-induced electric properties are
      investigated in detail. The devices demonstrate a remarkable response to 405 to
      780 nm light, a photocurrent that depends on the optical power and light
      wavelength, and an excellent photoswitching effect and stability. This implies
      that ZrS3 nanobelts are prospective candidates for high-performance nanoscale
      optoelectronic devices that may be practically applied in photodetection of
      visible to near infrared light. The facile fabrication method is extendable to
      flexible nanodevices with different nanostructures. 

PMID- 25048817
TI  - Testing commercial sex workers for sexually transmitted infections in Victoria,
      Australia: an evaluation of the impact of reducing the frequency of testing.
AB  - BACKGROUND: The frequency of testing sex workers for sexually transmitted
      infections (STIs) in Victoria, Australia, was changed from monthly to quarterly
      on 6 October 2012. Our aim was to determine the impact of this change to the
      clients seen at the Melbourne Sexual Health Centre (MHSC). METHODS: Computerised
      medical records of all clients attending at MHSC from 7 October 2011 to 7 October
      2013 were analysed. RESULTS: Comparing between the monthly and quarterly testing
      periods, the number of consultations at MSHC with female sex workers (FSW) halved
      from 6146 to 3453 (p<0.001) and the consultation time spent on FSW reduced by
      40.6% (1942 h to 1153 h). More heterosexual men (p<0.001), and women (p<0.001)
      were seen in the quarterly testing period. The number of STIs diagnosed in the
      clinic increased from 2243 to 2589 from the monthly to quarterly period,
      respectively [15.4% increase (p<0.001)]. Up to AU$247,000 was saved on FSW
      testing after the shift to quarterly testing. CONCLUSIONS: The change to STIs
      screening frequency for sex workers from monthly to quarterly resulted in a 15%
      increase in STI diagnoses in the clinic and approximate a quarter of a million
      dollars was diverted from FSW testing to other clients. Overall the change in
      frequency is likely to have had a beneficial effect on STI control in Victoria.

PMID- 25048819
TI  - Host tropism of infectious salmon anaemia virus in marine and freshwater fish
      species.
AB  - The aquatic orthomyxovirus infectious salmon anaemia virus (ISAV) causes a severe
      disease in farmed Atlantic salmon, Salmo salar L. Although some ISA outbreaks are
      caused by horizontal transmission of virus between farms, the source and
      reservoir of the virus is largely unknown and a wild host has been hypothesized.
      Atlantic salmon are farmed in open net-pens, allowing transmission of pathogens
      from wild fish and the surrounding environment to the farmed fish. In this study,
      a large number of fish species were investigated for ISAV host potential. For
      orthomyxoviruses, a specific receptor binding is the first requirement for
      infection; thus, the fish species were investigated for the presence of the ISAV
      receptor. The receptor was found to be widely distributed across the fish
      species. All salmonids expressed the receptor. However, only some of the cod-like
      and perch-like fish did, and all flat fish were negative. In the majority of the
      positive species, the receptor was found on endothelial cells and/or on red blood
      cells. The study forms a basis for further investigations and opens up the
      possibility for screening species to determine whether a wild host of ISAV
      exists. 

PMID- 25048820
TI  - Identification and characterization of microsatellite from Alternaria
      brassicicola to assess cross-species transferability and utility as a diagnostic
      marker.
AB  - Alternaria blight caused by Alternaria brassicicola (Schwein.) Wiltshire and A.
      brassicae (Berk.) Sacc., is one of the most important disease of rapeseed
      mustard, characterized by the formation of spots on leaves, stem, and siliquae
      with premature defoliation and stunting of growth. These two species are very
      difficult to differentiate based on disease symptoms or spore morphology.
      Therefore, the aim of present investigation was to identify and characterize
      transferable microsatellite loci from A. brassicicola to A. brassicae for the
      development of diagnostic marker. A total of 8,457 microsatellites were
      identified from transcript sequences of A. brassicicola. The average density of
      microsatellites was one microsatellite per 1.94 kb of transcript sequence
      screened. The most frequent repeat was tri-nucleotide (74.03 %), whereas penta
      nucleotide (1.14 %) was least frequent. Among amino acids, arginine (13.11 %)
      showed maximum abundance followed by lysine (10.11 %). A total of 32 alleles were
      obtained across the 31 microsatellite loci for the ten isolates of A.
      brassicicola. In cross-species amplifications, 5 of the 31 markers amplified the
      corresponding microsatellite regions in twenty isolates of A. brassicae and
      showed monomorphic banding pattern. Microsatellite locus ABS28 was highly
      specific for A. brassicicola, as no amplification was observed from twenty-nine
      other closely related taxa. Primer set, ABS28F/ABS28R, amplified a specific
      amplicon of 380 bp from all A. brassicicola isolates. Standard curves were
      generated for A. brassicicola isolate using SYBR Green I fluorescent dye for
      detection of amplification in real-time PCR assay. The lowest detection limit of
      assay was 0.01 ng. Thus, the primer set can be used as diagnostic marker to
      discriminate and diagnose A. brassicicola from synchronously occurring fungus, A.
      brassicae associated with rapeseed and mustard.

PMID- 25048822
TI  - Explanatory models of diabetes in urban poor communities in Accra, Ghana.
AB  - OBJECTIVES: The objective of the study was to examine explanatory models of
      diabetes and diabetes complications among urban poor Ghanaians living with
      diabetes and implications for developing secondary prevention strategies. DESIGN:
      Twenty adults with type 2 diabetes were recruited from three poor communities in
      Accra. Qualitative data were obtained using interviews that run between 40 and 90
      minutes. The interviews were audio-taped, transcribed and analysed thematically,
      informed by the 'explanatory model of disease' concept. RESULTS: Respondents
      associated diabetes and its complications with diet, family history, lifestyle
      factors (smoking, excessive alcohol consumption and physical inactivity),
      psychological stress and supernatural factors (witchcraft and sorcery). These
      associations were informed by biomedical and cultural models of diabetes and
      disease. Subjective experience, through a process of 'body-listening,'
      constituted a third model on which respondents drew to theorise diabetes
      complications. Poverty was an important mediator of poor self-care practices,
      including treatment non-adherence. CONCLUSIONS: The biomedical model of diabetes
      was a major source of legitimate information for self-care practices. However,
      this was understood and applied through a complex framework of cultural theories
      of chronic disease, the biopsychological impact of everyday illness experience
      and the disempowering effects of poverty. An integrated biopsychosocial approach
      is proposed for diabetes intervention in this research community.

PMID- 25048821
TI  - The evolution of speech: vision, rhythm, cooperation.
AB  - A full account of human speech evolution must consider its multisensory,
      rhythmic, and cooperative characteristics. Humans, apes, and monkeys recognize
      the correspondence between vocalizations and their associated facial postures,
      and gain behavioral benefits from them. Some monkey vocalizations even have a
      speech-like acoustic rhythmicity but lack the concomitant rhythmic facial motion
      that speech exhibits. We review data showing that rhythmic facial expressions
      such as lip-smacking may have been linked to vocal output to produce an ancestral
      form of rhythmic audiovisual speech. Finally, we argue that human vocal
      cooperation (turn-taking) may have arisen through a combination of volubility and
      prosociality, and provide comparative evidence from one species to support this
      hypothesis. 

PMID- 25048823
TI  - Confronting commercial sexual exploitation and sex trafficking of minors.

PMID- 25048824
TI  - Lower risk of hypoglycaemia and greater odds for weight loss with initiation of
      insulin detemir compared with insulin glargine in Turkish patients with type 2
      diabetes mellitus: local results of a multinational observational study.
AB  - BACKGROUND: The purpose of this analysis is to evaluate the safety and
      effectiveness of insulin initiation with once-daily insulin detemir (IDet) or
      insulin glargine (IGlar) in real-life clinical practice in Turkish patients with
      type 2 diabetes mellitus (T2DM). METHODS: This was a 24-week multinational
      observational study of insulin initiation in patients with T2DM. RESULTS: The
      Turkish cohort (n = 2886) included 2395 patients treated with IDet and 491 with
      IGlar. The change in glycosylated haemoglobin (HbA1c) from the pre-insulin levels
      was -2.21% [95% confidence interval (CI) -2.32, -2.09] in the IDet group and 
      1.88% [95% CI -2.17, -1.59] in the IGlar group at the final visit. The incidence
      rate of minor hypoglycaemia increased in both groups from the pre-insulin to the
      final visit (+0.66 and +2.23 events per patient year in the IDet and IGlar
      groups, respectively). Weight change in the IDet group was -0.23 kg [95% CI 
      0.49, 0.02 kg], and +1.55 kg [95% CI 1.11, 2.00 kg] in the IGlar group.
      Regression analysis with adjustment for previously identified confounders (age,
      gender, duration of diabetes, body mass index, previous history of hypoglycaemia,
      microvascular disease, number and change in oral anti-diabetic drug therapy,
      HbA1c at baseline and insulin dose) identified an independent effect of insulin
      type (IDet versus IGlar) with a risk of at least one episode of hypoglycaemia
      (odds ratio (OR): 0.33 [95% CI 0.21, 0.52], p <0.0001), and weight loss >=1 kg
      (OR: 1.75 [95% CI 1.18, 2.59], p = 0.005), but not on HbA1c (+0.05% [95% CI 
      0.15, 0.25%], p = 0.6). CONCLUSIONS: Initiation of basal insulin analogues, IDet
      and IGlar, were associated with clinically significant glycaemic improvements. A
      lower risk of minor hypoglycaemia and greater odds of weight loss >=1 kg was
      observed with IDet compared with IGlar. TRIAL REGISTRATION: NCT00825643 and
      NCT00740519.

PMID- 25048825
TI  - Quantitative analysis of carbon in cementite using pulsed laser atom probe.
AB  - Carbon quantification and the standardisation in a pure cementite were conducted
      using pulsed-laser atom probe tomography (APT). The results were analysed to
      investigate a dependence on three distinct experimental parameters; the laser
      pulse energy, the cryogenic specimen temperature and the laser pulse frequency.
      All the measurements returned an apparent carbon content of 25.0+/-1.0at%. Carbon
      content measurements showed no clear dependence on the cryogenic temperature or
      the laser pulse frequency. However, the results did demonstrate a strong
      correlation with the laser pulse energy. For lower laser pulse energies, the
      analysis returned carbon contents higher than the stoichiometric ratio. It was
      suggested that this effect is due to pile up of (56)Fe(++) at the detector and as
      a consequence there is a systematic preferential loss of these ions throughout
      the course of the experiment. Conversely, in experiments utilising higher laser
      pulse energies, it was found that the carbon contents were smaller than the
      stoichiometric ratio. In these experiments an increasing fraction of the larger
      carbon molecular ions (e.g., C5 ions) were detected as part of a multiple
      detection events, which could affect the quantification measurements. 

PMID- 25048827
TI  - Predicting and preventing visual impairment and blindness by incorporating
      individual progression velocity in glaucoma care.

PMID- 25048826
TI  - Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.
AB  - Lymph node metastasis indicates poor prognosis in esophageal cancer. To
      understand the underlying mechanisms, most studies so far focused on
      investigating the tumors themselves and/or invaded lymph nodes. However they
      neglected the potential events within the metastatic niche, which precede
      invasion. Here we report the first description of these regulations in patients
      on transcription level. We determined transcriptomic profiles of still metastasis
      free regional lymph nodes for two patient groups: patients classified as pN1 (n =
      9, metastatic nodes exist) or pN0 (n = 5, no metastatic nodes exist). All
      investigated lymph nodes, also those from pN1 patients, were still metastasis
      free. The results show that regional lymph nodes of pN1 patients differ
      decisively from those of pN0 patients--even before metastasis has taken place. In
      the pN0 group distinct immune response patterns were observed. In contrast, lymph
      nodes of the pN1 group exhibited a clear profile of reduced immune response and
      reduced proliferation, but increased apoptosis, enhanced hypoplasia and
      morphological conversion processes. DKK1 was the most significant gene associated
      with the molecular mechanisms taking place in lymph nodes of patients suffering
      from metastasis (pN1). We assume that the two molecular profiles observed
      constitute different stages of a progressive disease. Finally we suggest that
      DKK1 might play an important role within the mechanisms leading to lymph node
      metastasis.

PMID- 25048828
TI  - Author response: Predicting and preventing visual impairment and blindness by
      incorporating individual progression velocity in glaucoma care.

PMID- 25048829
TI  - Intermediates in the folding equilibrium of repeat proteins from the TPR family.
AB  - In recent decades, advances in computational methods and experimental biophysical
      techniques have improved our understanding of protein folding. Although some of
      these advances have been remarkable, the structural variability of globular
      proteins usually encountered makes it difficult to extract general features of
      their folding processes. To overcome this difficulty, experimental and
      computational studies of the folding of repeat (or modular) proteins are of
      interest. Because their native structures can be described as linear arrays of
      the same, repeated, supersecondary structure unit, it is possible to seek a
      possibly independent behavior of the different modules without taking into
      account the intrinsic stability associated with different secondary structure
      motifs. In this work we have used a Monte Carlo-based simulation to study the
      folding equilibrium of four repeat proteins belonging to the tetratricopeptide
      repeat family. Our studies provide new insights into their energy profiles,
      enabling investigation about the existence of intermediate states and their
      relative stabilities. We have also performed structural analyses to describe the
      structure of these intermediates, going through the vast number of conformations
      obtained from the simulations. In this way, we have tried to identify the regions
      of each protein in which the modular structure yields a different behavior and,
      more specifically, regions of the proteins that can stay folded when the rest of
      the chain has been thermally denatured.

PMID- 25048830
TI  - Facile synthesis of novel MoS2@SnO2 hetero-nanoflowers and enhanced
      photocatalysis and field-emission properties.
AB  - A novel hierarchical MoS2@SnO2 hetero-nanoflower was successfully synthesized by
      a facile, two-step hydrothermal method without using any additives or
      surfactants. One possible growth mechanism of the hetero-nanostructure was
      presented in detail based on OH(-) ion-dependent experimental facts. Due to the
      formation of the p-n junctions and the increased specific surface area in the
      composites, an outstanding photocatalytic activity of the as-prepared sample was
      obtained by monitoring the photodegradation of methylene blue (MB). According to
      the data, after irradiation for 100 min, the remaining MB in solution is about
      26% for MoS2 nanoflowers and 9.5% for MoS2@SnO2 hetero-nanoflowers. Moreover, an
      excellent field-emission performance was obtained from MoS2@SnO2 hetero
      nanoflower relative to the pure MoS2 with the turn-on field decreasing from 4.2 V
      MUm(-1) to 3.4 V MUm(-1) and the threshold field decreasing from 6.2 V MUm(-1) to
      5.2 V MUm(-1), which is mainly attributed to the increased field-emission points
      and MoS2-SnO2 heterojunction. 

PMID- 25048832
TI  - Economic impact profiling of CBRN events: focusing on biological incidents.
AB  - Chemical, biological, radiological and nuclear (CBRN) incidents, both caused
      accidentally by human error or natural/technological events and determined
      intentionally as criminal/malicious/terroristic acts, have consequences that
      could be differently characterized. In the last years many efforts to analyze the
      economic impact of terrorist threat have been carried out, while researches
      specifically concerning CBRN events have not been extensively undertaken. This
      paper in particular aims at proposing a methodological approach for studying
      macro-level economic impact profiles of biological incidents caused by weaponized
      and non-weaponized materials. The suggested approach investigates the economic
      consequences of biological incidents according to two main dimensions: type of
      large-scale effect and persistence of effect. Biological incident economic
      impacts are analyzed taking into account the persistence of effect during time as
      short-term impact (i.e. immediately after the incident), medium-term impact (i.e.
      by a month) and long-term impact (i.e. by years). The costs due to preventive
      countermeasure against biological threats (e.g. prevention, protection and
      preparedness expenses) are not taken into account. To this purpose, information
      on the key features of past biological incidents can be used as case studies to
      try to build impact profiles taking into account the proposed two main
      dimensions. Consequence management and effect mitigation of CBRN emergencies and
      disasters may benefit from an ex ante definition of the impact profiling related
      to this kind of incidents. The final goal of this paper is to define an approach
      to organize information on possible biological events according to their impact
      profile for supporting more effective and efficient first responders' prompt
      actions and policy makers' strategic decisions after the event occurrence. 

PMID- 25048831
TI  - Molecular and chemical engineering of bacteriophages for potential medical
      applications.
AB  - Recent progress in molecular engineering has contributed to the great progress of
      medicine. However, there are still difficult problems constituting a challenge
      for molecular biology and biotechnology, e.g. new generation of anticancer
      agents, alternative biosensors or vaccines. As a biotechnological tool,
      bacteriophages (phages) offer a promising alternative to traditional approaches.
      They can be applied as anticancer agents, novel platforms in vaccine design, or
      as target carriers in drug discovery. Phages also offer solutions for modern cell
      imaging, biosensor construction or food pathogen detection. Here we present a
      review of bacteriophage research as a dynamically developing field with promising
      prospects for further development of medicine and biotechnology.

PMID- 25048833
TI  - Management of new oral anticoagulants related life threatening or major bleedings
      in real life: a brief report.
AB  - Although new oral anticoagulants (NOAs) have been marketed in many countries,
      concern exists about the management of bleedings related to these drugs due to
      the lack of specific antidotes. The aim of our study was to report on real life
      management of NOAs-related life-threatening or major bleedings. We report data
      from consecutive cases of NOAs related major bleedings admitted to 4 hospitals
      since NOAs became marketed in Italy. We treated 8 patients, 4 males, with mean
      age 84 +/- 7 years, 7 of whom were on dabigatran and one on rivaroxaban. The
      indication for NOA was atrial fibrillation. All bleedings were spontaneous and
      involving the gastro-intestinal tract. At the time of bleeding all patients had a
      drop in hemoglobin levels over 20 g/L. Creatinine clearance was <=30 mL/min in 4
      patients. All patients received general supportive measures, 4 of 8 patients were
      transfused with packed red cells and one patient received platelet transfusion.
      Three patients were treated with tranexamic acid and one patient on dabigatran
      received 4-factor prothrombin complex concentrate (PCC) with bleeding cessation,
      although coagulation parameters were not corrected. The median time for
      normalization of coagulation parameters was 3 days (range 1-6 days). All patients
      were discharged alive and NOAs were discontinued. In NOAs related major gastro
      intestinal bleeding general supportive measures seem to be effective for the
      majority of patients. Despite promoting bleeding cessation, 4-factor PCC does not
      reverse abnormal coagulation parameters.

PMID- 25048834
TI  - Recurrent right ventricular takotsubo cardiomyopathy in a patient with recurrent
      aspiration.
AB  - Takotsubo cardiomyopathy is described as transient hypokinesis of the apical and
      mid-segments of the left ventricle with hypercontractile basal segments triggered
      by emotional or physical stress. Variants with basal hypokinesis and apical
      hyperkinesis have been described, as well as simultaneous involvement of the
      right ventricle (RV). Proposed mechanisms include myocardial "stunning" due to
      excessive catecholamine release. The echocardiographic presentation of Takotsubo
      cardiomyopathy may be related to differences in regional sympathetic innervation
      and catecholamine receptor density in the myocardium in the setting of high
      levels of circulating catecholamines. We describe the first case of isolated,
      recurrent RV Takotsubo cardiomyopathy reported in the literature. 

PMID- 25048835
TI  - Pulmonary lymph node charting in normal dogs with blue dye and   scintigraphic
      lymphatic mapping.
AB  - The prognosis of dogs with primary lung tumors and lymph node metastasis is
      poorer than of dogs without metastasis. Biopsy of intrathoracic lymph nodes is
      recommended, but without specific guidelines. This study investigated
      incorporation of a human lymph node classification in normal dogs with
      intercostal thoracotomies. Methylene blue and technetium-99m sulfur colloid lobar
      injections were used for enhanced nodal identification. Descriptive comparisons
      were made for lymph node resections utilizing both veterinary and human anatomic
      lymph node charts. Amedian of 2 (range 1-4) lymph nodes were removed per
      hemithorax in vivo versus a median 6.5 (range 2-8) lymph nodes removed ex vivo
      from each hemithorax following in vivo dissections. Incorporation of a human
      thoracic lymph node classification system may be useful for future clinical
      application in dogs. Future use of either methylene blue or technetium for canine
      thoracic lymphadenectomy needs to be evaluated further.

PMID- 25048836
TI  - First case report of ultrastructural cutaneous abnormalities in equine atopic
      dermatitis.
AB  - Atopic dermatitis (AD) is a common skin disease that affects humans and animals.
      Skin impairment has been described in human and canine AD. Equine AD is
      recognized in practice but little is known about its pathogenesis. As remarkable
      similarities exist across species in terms of cutaneous manifestations of AD, it
      was speculated that skin abnormalities may also exist in atopic horses. This case
      report describes the ultrastructure of the stratum corneum of two normal and two
      atopic horses. Biopsies were taken from sites predisposed to AD and examined
      using electron microscopy. Stratum corneum in normal samples was compacted with
      organized lipid lamellae while in atopic samples disorganized lipid lamellae,
      retained lamellar bodies and amorphous lipids were found. These changes are very
      similar to what reported in AD in other species. It is currently unknown whether
      these abnormalities in atopic horses are primary or secondary and their
      importance in allergen penetration. 

PMID- 25048837
TI  - Rapid testing and quantification of Salmonella in ileocaecal lymph nodes of
      Austrian pigs slaughtered for consumption.
AB  - Traditionally, quantitative microbial risk assessment (QMRA) is based on culture
      dependent technologies. However, molecular quantification could forge additional,
      detailed information. A prerequisite of quantitative real-time PCR in animal
      science is a tissue preparation method where large volumes of tissue material can
      be reduced and particularly target cells can be concentrated. An easy-to-use
      sample preparation method for food (Matrix-Lysis) was recently adapted to tissues
      and now permits quantification of target cells from up to 5 g of organic matrix.
      The aim of this study was to examine the suitability of Matrix-Lysis for
      quantification of Salmonella in porcine ileocaecal lymph nodes (ICLNs). After
      demonstrating constant recovery rates, ICLNs from 540 pigs were examined for
      Salmonella spp. with Matrix-Lysis. Samples were also analysed using ISO
      6579:2002, a combined enrichment/qPCR method and a lateral flow test. It could be
      shown that qPCR coupled with Matrix-Lysis can contribute to QMRA in food safety
      by enabling reproducible quantitative data, even at low contamination rates.

PMID- 25048839
TI  - The "weakness" link: can muscle impairment be identified as a cause of disability
      in rheumatology patients?

PMID- 25048838
TI  - A new model for predicting liver cirrhosis in chronic hepatitis B virus carriers
      with low serum alanine transaminase activity.
AB  - OBJECTIVES: To develop a cirrhosis-predicted model in chronic hepatitis B virus
      carriers with alanine transarninase (ALT) less than two times the upper limit of
      normal (ULN). METHODS: Treatment-naive patients (n=278), who had undergone liver
      biopsies, were randomly divided into two groups - a training group and a
      validation group. Thirteen bio-clinical parameters were analyzed. A liver
      cirrhosis-predicting model (PPT model) was constructed using multivariate
      analysis. The diagnostic value of the model was analyzed by the receiving
      operating characteristics (ROC) method and compared with other available models.
      RESULTS: A PPT model to predict liver cirrhosis was derived from three
      independent predictors of liver fibrosis [platelet count (PLT), prothrombin time
      (PT) and total bile acid (TBA)]. PPT model predicted cirrhosis with an area under
      the ROC (AUROC) curve of 0.83, a positive predictive value of 86.7% and a
      negative predictive value of 95.2%. Compared with APRI, FIB-4, age-AST model, AP
      index and APGA model, PPT model had the highest correlation coefficient (r=0.49)
      and greater predictive performance (AUROC of 0.83). CONCLUSIONS: The PPT model
      was accurate in predicting cirrhosis and may reduce the need for liver biopsy in
      chronic hepatitis B virus carriers with ALT less than two times ULN.

PMID- 25048840
TI  - Lysosomal enzymes in PD: further evidence is needed.

PMID- 25048841
TI  - Reactions of cycloaliphatic thioketones and their oxo analogues with lithiated
      methoxyallene: a new approach to vinylthiiranes.
AB  - Admantanethione smoothly reacted with lithiated methoxyallene at low temperatures
      yielding the expected allenyl-substituted thiolate, which upon aqueous work-up
      underwent spontaneous 1,3-cyclization to afford a hitherto unknown methoxy
      substituted vinylthiirane derivative. The analogous reaction with adamantanone
      led to the corresponding allenyl alcohol that can be isolated and--depending on
      the conditions applied--either be converted into the corresponding vinyloxirane
      or into the 2,5-dihydrofuran derivative. Sterically more crowded thioketones were
      also combined with lithiated methoxyallene, but in these cases competitive 1,5
      cyclization leading to isomeric dihydrothiophene derivatives was observed. DFT
      calculations of model intermediates and products show distinct energy differences
      of the sulfur and the corresponding oxygen compounds. Desulfurization of the
      adamantanethione-derived vinylthiirane yielded a methoxy-substituted 1,3-diene
      that was studied in cycloadditions with electron-deficient dienophiles. Whereas
      in the case of tetracyanoethylene the corresponding cyclobutane derivative was
      formed, the reaction with nitrosobenzene provided the expected 1,2-oxazine
      derivative. By reductive cleavage of the N-O bond this heterocycle was converted
      into an unsaturated amino alcohol bearing an adamantane moiety.

PMID- 25048843
TI  - Anatomists' views on human body dissection and donation: an international survey.
AB  - A survey was conducted to test three hypotheses: anatomists believe that
      dissection by students conveys not just anatomical knowledge but also essential
      skills and attitudes, including professionalism; anatomists approve of the
      donation of their own bodies or body parts/organs for medical/health-care
      training and research; attitudes towards body dissection and donation are not
      dependent upon gender or upon the extent of teaching experience, but are related
      to transcendental convictions relating to beliefs in the afterlife. Eighty-one
      anatomists, from 29 countries responded to the survey; 80% indicated that they
      required medical/health-care students to dissect human cadavers (60% females-86%
      males, p=0.02). Most teachers recorded that dissection was an instrument for
      training undergraduate students, an instrument for the development of
      professional skills, and an instrument to help to control emotions in the future
      doctor rather than being only a means of teaching/learning anatomy facts. Males
      were more receptive to the concept that dissection helps to control emotions in
      the future doctor (p=0.02). Most teachers (75%) said they were willing to donate
      their bodies, 41% saying they would donate body organs only, 9% would donate
      their entire bodies only, 25% would separately donate organs and also the entire
      body. The willingness to donate increased significantly with the years of
      teaching experience (p=0.04). Teachers who were not believers in the afterlife
      were more likely to donate their organs/bodies than were believers (p=0.03). Our
      findings showed that anatomists' attitudes towards body dissection and donation
      are dependent upon gender, upon the extent of teaching experience, and upon
      transcendental convictions.

PMID- 25048842
TI  - Genetic transformation of Fusarium avenaceum by Agrobacterium tumefaciens
      mediated transformation and the development of a USER-Brick vector construction
      system.
AB  - BACKGROUND: The plant pathogenic and saprophytic fungus Fusarium avenaceum causes
      considerable in-field and post-field losses worldwide due to its infections of a
      wide range of different crops. Despite its significant impact on the
      profitability of agriculture production and a desire to characterize the
      infection process at the molecular biological level, no genetic transformation
      protocol has yet been established for F. avenaceum. In the current study, it is
      shown that F. avenaceum can be efficiently transformed by Agrobacterium
      tumefaciens mediated transformation. In addition, an efficient and versatile
      single step vector construction strategy relying on Uracil Specific Excision
      Reagent (USER) Fusion cloning, is developed. RESULTS: The new vector construction
      system, termed USER-Brick, is based on a limited number of PCR amplified vector
      fragments (core USER-Bricks) which are combined with PCR generated fragments from
      the gene of interest. The system was found to have an assembly efficiency of 97%
      with up to six DNA fragments, based on the construction of 55 vectors targeting
      different polyketide synthase (PKS) and PKS associated transcription factor
      encoding genes in F. avenaceum. Subsequently, the DeltaFaPKS3 vector was used for
      optimizing A. tumefaciens mediated transformation (ATMT) of F. avenaceum with
      respect to six variables. Acetosyringone concentration, co-culturing time, co
      culturing temperature and fungal inoculum were found to significantly impact the
      transformation frequency. Following optimization, an average of 140 transformants
      per 106 macroconidia was obtained in experiments aimed at introducing targeted
      genome modifications. Targeted deletion of FaPKS6 (FA08709.2) in F. avenaceum
      showed that this gene is essential for biosynthesis of the
      polyketide/nonribosomal compound fusaristatin A. CONCLUSION: The new USER-Brick
      system is highly versatile by allowing for the reuse of a common set of building
      blocks to accommodate seven different types of genome modifications. New USER
      Bricks with additional functionality can easily be added to the system by future
      users. The optimized protocol for ATMT of F. avenaceum represents the first
      reported targeted genome modification by double homologous recombination of this
      plant pathogen and will allow for future characterization of this fungus.
      Functional linkage of FaPKS6 to the production of the mycotoxin fusaristatin A
      serves as a first testimony to this.

PMID- 25048844
TI  - Age-related alterations in the lacrimal gland of adult albino rat: a light and
      electron microscopic study.
AB  - BACKGROUND: Age related changes in the lacrimal gland are associated with
      alterations in the structural organization and functional response in the gland
      of diverse mammalian species. Dry eye syndrome is one of the most common ocular
      problems in the world especially in old age. It results when the lacrimal gland
      fails to secrete proteins and fluid in sufficient quantity or appropriate
      composition. AIM OF THE WORK: The present study is designed to demonstrate the
      influence of aging on the structure of the lacrimal gland of albino rat and to
      provide a morphological basis to explain the pathogenesis of the dry eye syndrome
      with ageing. It also aims to carry out a comparative analysis of age-dependent
      changes in male and female rats and to address how the lacrimal gland ages in
      each sex. MATERIAL AND METHODS: Eighty albino rats were used in this study. The
      animals were divided into two age groups, young adult and senile. Tear secretion
      was measured using a modified Schirmer test. Corneal impression cytology of the
      anesthetized rats was done. The glands were subjected to gross morphologic
      examination, microscopic examination using H&E, PAS, Masson's trichrome and
      Giemsa stains. Electron microscopic examination was done in addition to
      quantitative histomorphometric estimations included acinar density, ductal count
      and mast cell count. RESULTS: Light microscopic examination of the lacimal glands
      of the senile rats revealed different pathological changes. These included
      acinar, ductal as well as stromal changes. Electron microscope examination of the
      lacrimal gland of the senile group showed a decrease in the electron dense
      secretory vesicles, mitochondrial swelling and lipofuscin-like inclusions were
      frequently seen in the cytoplasm of acinar cells in senile rats. CONCLUSION: The
      structural changes in the lacrimal glands of senile rats were associated with
      reduction in tear secretion as well as alterations in corneal epithelium. Gender
      difference in lacrimal gland structure was recorded.

PMID- 25048845
TI  - Preformed frequencies of cytomegalovirus (CMV)-specific memory T and B cells
      identify protected CMV-sensitized individuals among seronegative kidney
      transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection remains a major complication after
      kidney transplantation. Baseline CMV risk is typically determined by the
      serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies,
      even though T-cell responses to major viral antigens are crucial when controlling
      viral replication. Some IgG-seronegative patients who receive an IgG-seropositive
      allograft do not develop CMV infection despite not receiving prophylaxis. We
      hypothesized that a more precise evaluation of pretransplant CMV-specific immune
      sensitization using the B and T-cell enzyme-linked immunospot assays may identify
      CMV-sensitized individuals more accurately, regardless of serological evidence of
      CMV-specific IgG titers. METHODS: We compared the presence of preformed CMV
      specific memory B and T cells in kidney transplant recipients between 43 CMV IgG
      seronegative (sR(-)) and 86 CMV IgG-seropositive (sR(+)) patients. Clinical
      outcome was evaluated in both groups. RESULTS: All sR(+) patients showed a wide
      range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell
      frequencies were also clearly detected in 30% of sR(-) patients, and those with
      high CMV-specific T-cell frequencies had a significantly lower incidence of late
      CMV infection after prophylactic therapy. Receiver operating characteristic curve
      analysis for predicting CMV viremia and disease showed a high area under the
      receiver operating characteristic curve (>0.8), which translated into a high
      sensitivity and negative predictive value of the test. CONCLUSIONS: Assessment of
      CMV-specific memory T- and B-cell responses before kidney transplantation among
      sR(-) recipients may help identify immunized individuals more precisely, being
      ultimately at lower risk for CMV infection.

PMID- 25048846
TI  - Findings in patients from Benin with osteomyelitis and polymerase chain reaction
      confirmed Mycobacterium ulcerans infection.
AB  - BACKGROUND: Mycobacterium ulcerans is known to cause Buruli ulcer (BU), a
      necrotizing skin disease leading to extensive cutaneous and subcutaneous
      destruction and functional limitations. However, M. ulcerans infections are not
      limited to skin, and osteomyelitis, still poorly described in the literature,
      occurs in numerous young patients in Africa. METHODS: In a retrospective matched
      case-control study conducted in a highly endemic area in Benin, we analyzed
      demographic, clinical, biological, and radiological features in all patients with
      M. ulcerans infections with bone involvement, identified from a cohort of 1257
      patients with polymerase chain reaction-proved M. ulcerans infections. RESULTS:
      The 81 patients studied had a median age of 11 years (interquartile range, 7-16
      years) and were predominantly male (male-female ratio, 2:1). Osteomyelitis was
      observed beneath active BU lesions (60.5%) or at a distance from active or
      apparently healed BU lesions (14.8%) but also in patients without a history of BU
      skin lesions (24.7%). These lesions had an insidious course, with nonspecific
      clinical findings leading to delayed diagnosis. A comparison with findings in 243
      age- and sex-matched patients with BU without osteomyelitis showed that case
      patients were less likely to have received BCG immunization than controls (33.3%
      vs 52.7%; P = .01). They were also at higher risk of longer hospital stay (118 vs
      69 days; P = .001), surgery (92.6% vs 63.0%; P = .001), and long-term crippling
      sequelae (55.6% vs 15.2%; P < .001). CONCLUSIONS: This study highlighted the
      difficulties associated with diagnosis of M. ulcerans osteomyelitis, with one
      fourth of patients having no apparent history of BU skin lesions, including
      during the current course of illness. Delays in treatment contributed to the high
      proportion (55.6%) of patients with crippling sequelae.

PMID- 25048847
TI  - Antifungal combination therapy for invasive aspergillosis.
AB  - The outcome of invasive aspergillosis (IA) continues to be associated with
      significant attributable mortality, especially in patients with hematological
      malignancies and in hematopoietic stem cell transplant recipients. In this
      context, antifungal combined therapy (ACT) has become an emerging strategy
      against IA. In an attempt to evaluate the benefits of ACT, a large number of
      experimental studies, clinical series, and randomized trials have been performed,
      with varying results. In addition, several controlled trials have been
      registered; however, in most cases, their final results have not been made
      available. In summary, there is an imbalance between the lack of published
      evidence regarding the benefits of ACT and its extensive and increasing use in
      current clinical practice, despite its associated cost. Here, we present a
      critical analysis of the available information regarding ACT for the treatment of
      IA as well as the authors' opinion with respect to its use.

PMID- 25048849
TI  - Rotavirus vaccines in routine use.
AB  - Vaccines are now available to combat rotavirus, the most common cause of severe
      diarrhea among children worldwide. We review clinical trial data for available
      rotavirus vaccines and summarize postlicensure data on effectiveness, impact, and
      safety from countries routinely using these vaccines in national programs. In
      these countries, rotavirus vaccines have reduced all-cause diarrhea and rotavirus
      hospitalizations by 17%-55% and 49%-92%, respectively, and all-cause diarrhea
      deaths by 22%-50% in some settings. Indirect protection of children who are age
      ineligible for rotavirus vaccine has also been observed in some high and upper
      middle income countries. Experience with routine use of rotavirus vaccines in
      lower middle income countries has been limited to date, but vaccine introductions
      in such countries have been increasing in recent years. The risk-benefit analysis
      of rotavirus vaccines is extremely favorable but other strategies to improve the
      effectiveness of the vaccine, particularly in lower middle income settings,
      should be considered. 

PMID- 25048848
TI  - Immunogenicity of intradermal trivalent influenza vaccine with topical imiquimod:
      a double blind randomized controlled trial.
AB  - BACKGROUND: Imiquimod, a synthetic Toll-like receptor 7 agonist enhanced
      immunogenicity of influenza vaccine in a mouse model. We hypothesized that
      topical imiquimod before intradermal influenza vaccination (TIV) would produce
      similar effect in human. METHODS: We performed a prospective 1-year follow-up,
      double-blind, randomized, controlled trial with adults with comorbidities.
      Participants were randomized to 1 of the following 3 vaccinations: topical 5% 250
      mg imiquimod ointment followed by intradermal TIV, topical aqueous-cream followed
      by intradermal TIV, or topical aqueous-cream followed by intramuscular TIV.
      Patients and investigators were blinded to the type of topical treatment applied.
      Hemagglutination inhibition (HI) and microneutralization antibody titers were
      measured. The primary outcome was the day 7 seroconversion rate. RESULTS: Ninety
      one recruited participants completed the study. The median age was 73 years. On
      day 7, 27/30 (90%) patients who received imiquimod and intradermal TIV achieved
      seroconversion against the H1N1 strain by HI, compared with 4/30 (13.3%) who
      received aqueous-cream and intramuscular TIV (P < .001), and 12/31 (38.7%) who
      received aqueous-cream and intradermal TIV (P < .001). The seroconversion,
      seroprotection, and geometric mean titer-fold increase were met in all 3 strains
      in the imiquimod and intradermal TIV group 2 weeks earlier, and the better
      seroconversion rate was sustained from day 7 to year 1 (P <= .001). The better
      immunogenicity was associated with fewer hospitalizations for influenza or
      pneumonia (P < .05). All adverse reactions were self-limited. CONCLUSIONS:
      Pretreatment with topical imiquimod significantly expedited, augmented, and
      prolonged the immunogenicity of influenza vaccination. This strategy for
      influenza immunization should be considered for the elderly population.

PMID- 25048850
TI  - Predictive utility of prior positive urine cultures.
AB  - BACKGROUND: A patient's prior urine cultures are often considered when choosing
      empiric antibiotic therapy for a suspected urinary tract infection. We sought to
      evaluate how well previous urine cultures predict the identity and susceptibility
      of organisms in a patient's subsequent urine cultures. METHODS: We conducted a
      multinational, multicenter, retrospective cohort study, including 22 019 pairs of
      positive urine cultures from 4351 patients across 2 healthcare systems in
      Toronto, Ontario, and Chicago, Illinois. We examined the probability of the same
      organism being identified from the same patient's positive urine culture as a
      function of time elapsed from the previous positive urine specimen; in cases
      where the same organism was identified we also examined the likelihood of the
      organism exhibiting the same or better antimicrobial susceptibility profile.
      RESULTS: At 4-8 weeks between cultures, the correspondence in isolate identity
      was 57% (95% confidence interval [CI], 55%-59%), and at >32 weeks it was 49% (95%
      CI, 48%-50%), still greater than expected by chance (P < .001). The
      susceptibility profile was the same or better in 83% (95% CI, 81%-85%) of isolate
      pairs at 4-8 weeks, and 75% (95% CI, 73%-77%) at >32 weeks, still greater than
      expected by chance (P < .001). Despite high local rates of ciprofloxacin
      resistance in urine isolates across all patients (40%; 95% CI, 39.5%-40.5%),
      ciprofloxacin resistance was <20% among patients with a prior ciprofloxacin
      sensitive organism and no subsequent fluoroquinolone exposure. CONCLUSIONS: A
      patient's prior urine culture results are useful in predicting the identity and
      susceptibility of a current positive urine culture. In areas of high
      fluoroquinolone resistance, ciprofloxacin can be used empirically when prior
      urine culture results indicate a ciprofloxacin-susceptible organism and there has
      been no history of intervening fluoroquinolone use.

PMID- 25048851
TI  - Efficacy and safety of fosfomycin plus imipenem as rescue therapy for complicated
      bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a
      multicenter clinical trial.
AB  - BACKGROUND: There is an urgent need for alternative rescue therapies in invasive
      infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We
      assessed the clinical efficacy and safety of the combination of fosfomycin and
      imipenem as rescue therapy for MRSA infective endocarditis and complicated
      bacteremia. METHODS: The trial was conducted between 2001 and 2010 in 3 Spanish
      hospitals. Adult patients with complicated MRSA bacteremia or endocarditis
      requiring rescue therapy were eligible for the study. Treatment with fosfomycin
      (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The
      primary efficacy endpoints were percentage of sterile blood cultures at 72 hours
      and clinical success rate assessed at the test-of-cure visit (45 days after the
      end of therapy). RESULTS: The combination was administered in 12 patients with
      endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia.
      Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and
      sequential antibiotics in 5. Blood cultures were negative 72 hours after the
      first dose of the combination in all cases. The success rate was 69%, and only 1
      of 5 deaths was related to the MRSA infection. Although the combination was safe
      in most patients (94%), a patient with liver cirrhosis died of multiorgan failure
      secondary to sodium overload. There were no episodes of breakthrough bacteremia
      or relapse. CONCLUSIONS: Fosfomycin plus imipenem was an effective and safe
      combination when used as rescue therapy for complicated MRSA bloodstream
      infections and deserves further clinical evaluation as initial therapy in these
      infections.

PMID- 25048852
TI  - Avoiding the perfect storm: the biologic and clinical case for reevaluating the 7
      day expectation for methicillin-resistant Staphylococcus aureus bacteremia before
      switching therapy.
AB  - Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB)
      is associated with poor outcomes and serious complications. The MRSA guidelines
      define treatment failure and persistent bacteremia as lasting >=7 days; however,
      this definition requires reevaluation. Aggressively reducing the bacterial
      inoculum promptly is critical because factors already in place before clinical
      presentation are driving resistance to the few antibiotics that are available to
      treat MRSAB. Alternative approaches to treat MRSAB should be considered within 3
      4 days of persistent MRSAB. With rapid molecular diagnostics emerging in clinical
      microbiology laboratories and biomarkers as a potential for early patient risk
      stratification, a future shorter threshold may become possible.

PMID- 25048853
TI  - A systematic review: can one prescribe carbapenems to patients with IgE-mediated
      allergy to penicillins or cephalosporins?
AB  - BACKGROUND: Cross-reactivity between penicillins or cephalosporins and
      carbapenems is anticipated as all have a beta lactam ring. However, the true
      incidence of immunoglobulin (Ig)E-mediated cross-reactivity is not known.
      METHODS: A systematic review was conducted to collect and combine all published
      data on children and adults reported to have a clinical history of IgE-mediated
      hypersensitivity to a penicillin and/or cephalosporin who were subsequently given
      a carbapenem. Reactions were classified as proven, suspected, or possible IgE
      mediated and non-IgE-mediated. RESULTS: Ten studies and 12 case reports
      describing 854 participants fit the study criteria. For patients with previous
      proven, suspected, or possible IgE-mediated penicillin reactions (N = 838), the
      incidence of any type of suspected hypersensitivity reaction to a carbapenem was
      36/838 (4.3%; 95% confidence interval [CI], 3.1%-5.9%) and the incidence of
      proven (1/838), suspected (0/838), or possible (19/838) IgE-mediated reactions
      was 20/838 (2.4%; 95% CI, 1.6%-3.7%). Of the subset of patients with positive
      penicillin skin tests (n = 295), only 1 had a hypersensitivity reaction (0.3%;
      95% CI, .06%-1.9%), and this was a possible IgE-mediated reaction. For patients
      with previous proven, suspected, or possible IgE-mediated cephalosporin reactions
      (N = 12), the incidence of any type of hypersensitivity reaction to a carbapenem
      was 3/12 (25%); this included 2 non-IgE-mediated reactions and 1 possible IgE
      mediated reaction. CONCLUSIONS: The cross-reactivity between penicillins and
      carbapenems for IgE-mediated reactions is very low, but caution is still advised.
      Cross-reactivity rates may be higher between cephalosporins and carbapenems;
      however, minimal data are available.

PMID- 25048854
TI  - Pre-exposure to low-power diode laser irradiation promotes cytoprotection in the
      rat retina.
AB  - The aim of this study was to investigate whether pre-exposure to low-power laser
      irradiation can provoke an effect on cellular protection in the rat retina. The
      right eyes of 40 rats were exposed to a 3-mm diode laser beam for 1 min in
      different light intensities and different experimental sets: group A low power of
      60 mW (34.27 J/cm(2) on the retina in consideration of the energy losses along
      the optical pathway) prior to high power of 80 mW (44.88 J/cm(2) on the retina in
      consideration of the energy losses along the optical pathway), group B high
      power, group C low power, group D (the left eyes from the counterpart of group A)
      and group E (untreated rat eyes) as controls. Morphological retinal change
      retinas were assessed using light microscopy and/or transmission electron
      microscopy. Heat shock protein (Hsp) 70 and cleaved caspase 3 protein expression
      were analyzed by immunohistochemical staining and Western blot. Cellular injury
      was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) assay. Hsp 70 expression in the inner plexiform layer and the
      outer plexiform layer in group A were 73.09 +/- 6.49 and 78.03 +/- 3.05%,
      respectively, which was significantly higher (P < 0.05) than those observed in
      group B (59.07 +/- 1.40 and 32.25 +/- 4.26%, respectively). The Hsp70/beta-actin
      ratio was 0.49 +/- 0.06 in group C, which was significantly higher (P < 0.05)
      than that of group B (0.27 +/- 0.04). Cleaved caspase 3 expression in group C
      both was significantly lower than that observed in group B. TUNEL staining showed
      that positive cells in the outer nuclear layer and inner nuclear layer in group A
      were significantly lower than those of group B. Pre-exposure to a 60-mW (34.27
      J/cm(2) on the retina) power laser irradiation stimulates a hyperexpression of
      Hsp70 together with a hypoexpression of cleaved caspase 3 in rat retina, which
      may suggest a cellular protective effect.

PMID- 25048856
TI  - Conservative treatment of bilateral condylar fractures in children: case report
      and review of the literature.
AB  - Two children (11 year old) with bilateral condylar fractures associated with
      symphysis fracture were conservatively treated. Both of them were followed up for
      about 1 year. A review of 21 cases of bilateral condylar fracture available in
      the literature revealed the younger the patient, the better the outcome of TMJ
      function or in radiographic remodeling. However, the longer the time elapsed, the
      higher the incidence of remodeling deformity and dysfunction. Thus, it must be
      better that a close follow-up of bilateral condylar fracture in children should
      be continued until the end of growth period. 

PMID- 25048855
TI  - Experimental study on the vascular thermal response to visible laser pulses.
AB  - Port-wine stains (PWSs) are congenital vascular malformations that progressively
      darken and thicken with age, and laser therapy is the most effective in clinical
      practice. Using dorsal skin chamber (DSC), this study evaluated thermal response
      of blood vessel to a 595-nm pulsed dye laser (PDL) with controlled energy doses
      and pulse durations. Totally, 32 vessels (30~300 MUm in diameter) are selected
      from the dorsal skin of the mouse to match those in port-wine stain. The
      experimental results showed that the thermal response of the blood vessels to
      laser irradiation can be recognized as coagulation, constriction with diameter
      decrease, disappearance (complete constriction), hemorrhage, and collagen damage
      in the order of increasing laser radiant exposure. Blood vessels with small
      diameter would response poorly and survive from the laser heating because their
      thermal relaxation time is much shorter than the pulse duration. The
      optimalradiant exposure is from 10 to 12 J/cm(2) under 6 ms pulse duration
      without considering the epidermal light absorption. Numerical simulations were
      also conducted using a 1,000-MUm deep Sprague-Dawley (SD) mouse skinfold. The
      light transportation and heat diffusion in dorsal skin were simulated with the
      Monte Carlo method and heat transfer equation, while the blood vessel
      photocoagulation was evaluated by Arrhenius-type kinetic integral. Both
      experimental observation and numerical simulation supported that hemorrhage is
      the dominant thermal response, which occurs due to preferential heating of the
      superior parts of large blood vessels. In clinical practice for 595 nm PDL, the
      consequent purpura caused by hemorrhage can be used as a treatment end point.

PMID- 25048857
TI  - Use of botulinum toxin in pediatric otolaryngology and laryngology.
AB  - The use of botulinum toxin in adult otolaryngology has been commonly used in
      conditions such as spasmodic dysphonia, cricopharyngeal spasm, palatal myoclonus,
      sialorrhea, and for cosmetic reasons. The current use of botulinum toxin in
      pediatric otolaryngology and laryngology has primarily been off label and in
      children older than 2 years of age. This review discusses the different
      applications of botulinum toxin in pediatric patients and its effectiveness in
      treating different pediatric conditions. 

PMID- 25048858
TI  - "Extended" Sistrunk procedure in the treatment of recurrent thyroglossal duct
      cysts: a 10-year experience.
AB  - OBJECTIVE: We report a 10-year experience of children with recurrent thyroglossal
      duct cysts (TGDCs) who have been treated using the "extended" Sistrunk procedure.
      METHODS: We performed a retrospective review of TGDC surgery from 2004 to 2013.
      Sistrunk operation was the procedure of choice in all patients. Seven children
      had TGDC recurrence. All of them underwent "extended" Sistrunk procedure. Follow
      up ranged from 6 months to 8 years. RESULTS: There were no gender differences,
      all recurrences presented within 12 months follow-up in the same location of the
      primary cyst. Five out of 7 (71%) patients have been treated for preoperative and
      2/7 (29%) for postoperative infection at the time of primary surgery.
      Pathological examination of the surgical specimens showed a single tract in 2
      children (29%) and multiple tracts in 5 (71%). We did not observe postoperative
      complications or further recurrences. CONCLUSION: Our experience suggest that
      recurrent TGDCs are equally common in both sexes, develop in the same location of
      the primary cyst and recur more commonly after perioperative infections. The
      "extended" Sistrunk procedure is highly effective and safe in treating recurrent
      TGDCs also if multiple duct tracts are detected.

PMID- 25048859
TI  - Role of endothelin-1/endothelin receptor signaling in fibrosis and calcification
      in nephrogenic systemic fibrosis.
AB  - Nephrogenic systemic fibrosis (NSF) is characterized by systemic fibrosis and
      abnormal calcification in patients with severe renal dysfunction. It is
      considered that gadolinium (Gd)-containing contrast agents used for magnetic
      resonance imaging trigger the development of NSF. However, the causative role of
      Gd and the mechanism of Gd-induced fibrosis and calcification in NSF are unknown.
      Recently, it has been known that endothelin-1 (ET-1)/ET receptor (ETR) signalling
      regulates fibrosis and calcification. The objective was to elucidate the role of
      ET-1/ETR signalling in Gd-induced fibrosis and calcification in NSF. First, we
      demonstrated that Gd enhanced proliferation and calcification of human adipose
      tissue-derived mesenchymal stem cells (hMSC) in vitro. Next, we examined the
      expression of ET-1 and ETR-A in hMSC using proliferation or calcification assay.
      ET-1 and ETR-A expression in hMSC treated with Gd were elevated. ET-1/ETR
      signalling inhibitor, bosentan, inhibited Gd-induced proliferation and
      calcification of hMSC. In addition, bosentan inhibited Gd-induced phosphorylation
      of ERK and Akt in hMSC. Plasma ET-1 levels of the patients were significantly
      higher than these of normal individuals and systemic sclerosis patients. In
      immunofluorescence staining, the expression of ETR-A in fibroblasts in dermal
      fibrosis lesion of NSF was increased. We conclude that Gd induces proliferation
      and calcification of hMSC via enhancement of ET-1/ETR signalling. Our results
      contribute to understand the pathogenesis of NSF. 

PMID- 25048861
TI  - Incontinence: Artificial urinary sphincter more likely to fail in compromised
      urethras.

PMID- 25048862
TI  - Prostate cancer: Unravelling bias in vasectomy associations.

PMID- 25048860
TI  - Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers.
AB  - Despite nearly two decades passing since the discovery of gene fusions involving
      TFE3 or TFEB in sporadic renal cell carcinoma (RCC), the molecular mechanisms
      underlying the renal-specific tumorigenesis of these genes remain largely
      unclear. The recently published findings of The Cancer Genome Atlas Network
      reported that five of the 416 surveyed clear cell RCC tumours (1.2%) harboured
      SFPQ-TFE3 fusions, providing further evidence for the importance of gene fusions.
      A total of five TFE3 gene fusions (PRCC-TFE3, ASPSCR1-TFE3, SFPQ-TFE3, NONO-TFE3,
      and CLTC-TFE3) and one TFEB gene fusion (MALAT1-TFEB) have been identified in RCC
      tumours and characterized at the mRNA transcript level. A multitude of molecular
      pathways well-described in carcinogenesis are regulated in part by TFE3 or TFEB
      proteins, including activation of TGFbeta and ETS transcription factors, E
      cadherin expression, CD40L-dependent lymphocyte activation, mTORC1 signalling,
      insulin-dependent metabolism regulation, folliculin signalling, and
      retinoblastoma-dependent cell cycle arrest. Determining which pathways are most
      important to RCC oncogenesis will be critical in discovering the most promising
      therapeutic targets for this disease. 

PMID- 25048863
TI  - Prostate cancer: Predicting response to androgen receptor signalling inhibition.

PMID- 25048864
TI  - Bladder cancer: Defining intermediate-risk non-muscle-invasive bladder cancer.

PMID- 25048866
TI  - History of photodynamic therapy in Great Britain.
AB  - Although the concept photodynamic therapy has been recognised for over a century,
      it is only over the last 25 years that it has been used in Great Britain. The
      first applications in the UK were in 1981 by John Carruth, who treated patients
      with advanced ENT and skin cancers. The following year, he and Stephen Bown set
      up the British Medical Laser Association (BMLA). Since that time, the use of PDT
      in the UK has slowly expanded in all fields of medicine and surgery. In 1986,
      Bown set up the National Medical Laser Centre (NMLC) and later collaborated with
      Liverpool gastroenterologist, Neville Krasner, in animal studies on rat colon. In
      1997, Keyvan Moghissi founded the Yorkshire Laser Centre (YLC) and began treating
      patients with advanced inoperable bronchial and oesophageal cancers. Stan Brown
      in Leeds set up the Centre for Photobiology and Photodynamic Therapy at the
      University of Leeds, working in close collaboration with the Yorkshire Cancer
      Research Centre. Other pioneers include Hugh Barr in Gloucester, Colin Hopper in
      London, Grant Fullarton in Glasgow and Roger Ackroyd, Malcolm Reed and Nicky
      Brown in Sheffield. PDT has now been used in the UK in the treatment of skin,
      oral, ENT, oesophageal, lung, bladder and gynaecological malignancies. 

PMID- 25048865
TI  - Quantification of pizza baking properties of different cheeses, and their
      correlation with cheese functionality.
AB  - The aim of this study is to quantify the pizza baking properties and performance
      of different cheeses, including the browning and blistering, and to investigate
      the correlation to cheese properties (rheology, free oil, transition temperature,
      and water activity). The color, and color uniformity, of different cheeses
      (Mozzarella, Cheddar, Colby, Edam, Emmental, Gruyere, and Provolone) were
      quantified, using a machine vision system and image analysis techniques. The
      correlations between cheese appearance and attributes were also evaluated, to
      find that cheese properties including elasticity, free oil, and transition
      temperature influence the color uniformity of cheeses. 

PMID- 25048867
TI  - The potential for photodynamic therapy in the treatment of localized infections.
AB  - At the present time photodynamic therapy (PDT) is receiving considerable interest
      for its potential as an antimicrobial therapy. This treatment may be a valuable
      tool in achieving a rapid reduction of the microbial burden perhaps even in the
      management of localized infections that are resistant to standard antibiotic
      regimens. A variety of photosensitizers from different groups including
      porphyrins, chlorophyll derivatives, phthalocyanines and azines have been
      effective in the photokilling of many Gram-positive and Gram-negative bacterial
      pathogens in addition to parasites, fungi, and viruses. Much of the suggested
      antimicrobial uses of this therapy are based on results from in vitro studies.
      Only a limited number of animal models of infection or clinical studies have been
      employed to assess the effectiveness of PDT. These studies have reported moderate
      successes that have not quite achieved the expectations projected from the in
      vitro results. In order to fully validate the potential of PDT as an
      antimicrobial therapy considerably more effort is required in the area of
      appropriate experimental models to better understand the mechanisms of
      photodynamic destruction of bacteria. 

PMID- 25048868
TI  - The development of phenothiazinium photosensitisers.
AB  - Methylene blue has been widely used since the late 19th century in biomedical
      research, and was the lead compound in several important clinical areas,
      including therapeutics for malaria and schizophrenia. The photodynamic therapy
      (PDT) of cancer and, more recently, of microbial infection (photodynamic
      antimicrobial chemotherapy (PACT)) has also employed methylene blue and its
      congeners, among other chemical types, due to the low human toxicities and
      efficient photosensitising properties of the group. However, little work has been
      carried out in terms of derivative and structure-activity development, most
      reports covering standard, commercially available compounds. This review deals
      with the evolution of phenothiazinium photosensitisers for both PACT and PDT use.

PMID- 25048869
TI  - Systemic photodynamic therapy with Photofrin for naevoid basal cell carcinoma
      syndrome-A pilot study.
AB  - BACKGROUND: Treatment of basal cell carcinomas in naevoid basal cell carcinoma
      syndrome (NBCCS) poses several challenges. The sheer numbers of such lesions in
      these patients makes traditional therapeutic modalities like surgery,
      impractical. Topical photodynamic therapy (PDT) with delta-5-amino levulinic acid
      has increasingly been recognised as and safe and effective choice in the
      treatment of BCC. The probability of local control of BCC treated by PDT depends
      strongly on lesion thickness, thick nodular lesions being less responsive.
      Response to treatment is monitored by the reduction in the lesional size, but
      histopathological confirmation of regression is often required. METHOD: We used
      systemic photodynamic therapy with Porfimer Sodium (Photofrin((r)), Axcan Pharma
      Inc., Quebec, Canada), a systemic photosensitizer for treating multiple BCC in
      seven patients with NBCCS. Treatment response was monitored using a high
      resolution 20MHz ultrasound. RESULTS: There was a substantial reduction in the
      number of superficial basal cell carcinomas with complete US regression after one
      treatment. A 74.2% reduction was seen in the size of thick lesions treated with
      external light. Thick nodular lesions in two patients treated with interstitial
      optical diffuser fibres in addition to external light showed 87.6% reduction in
      size as measured by high resolution ultrasound. CONCLUSIONS: Our preliminary
      results indicate that systemic photodynamic therapy using Photofrin and external
      light either alone or with interstitial optical diffuser fibres; may be effective
      in treatment of multiple, thick and nodular BCC lesions in Naevoid basal cell
      carcinoma syndrome. Further studies are needed to confirm our observations. We
      found high resolution ultrasound an effective alternative to histopathological
      analysis in monitoring the response to treatment.

PMID- 25048870
TI  - The influence of photodynamic therapy on the immune response.
AB  - Photodynamic therapy (PDT) is a clinically approved therapeutic modality used for
      the management of several types of tumors as well as non-malignant diseases. Most
      of the effects of this treatment regimen result from direct action of singlet
      oxygen and reactive oxygen species. However, accumulating evidence indicates that
      antitumor effects are also mediated by indirect stimulation of inflammatory and
      immune responses. These responses include rapid local infiltration of tumors by
      neutrophils and macrophages accompanied by systemic release of inflammatory
      mediators. This early response can initiate and translate into a more precise
      immune reaction that involves activation of specific T lymphocytes that seem to
      be necessary for the ultimate control of residual tumor cells. Although still
      incompletely understood, PDT can not only activate but also suppress the immune
      response depending on several variables. This review summarizes the influence of
      PDT on the immune response and discusses its importance in the management of
      human diseases. 

PMID- 25048871
TI  - ALA-induced porphyrin formation and fluorescence in synovitis tissue In-vitro and
      in vivo studies.
AB  - The synovial inflammatory process in rheumatoid arthritis (RA) is accompanied by
      massive tumor-like proliferation and activation of the connective stroma. These
      abnormal cells actively invade and destroy the peri-articular bone and cartilage
      at the margins of joints where synovium and bone are attached. There is still a
      lack of minimally invasive synovectomy methods, which might be suitable for the
      smaller joints. Unfortunately, these joints are usually involved in the disease.
      Photodynamic therapy has been evaluated as a possible treatment modality for RA
      synovitis. The present study describes the differences of 5-aminolevulinic acid
      (5-ALA) and 5-ALA ester-induced protoporphyrin IX (PpIX) production in cell
      cultures obtained from patients with RA, osteoarthritis (OA) and human sarcoma
      cell line (HS 192.T) and in a collagen-induced arthritis model in rats. The
      incubation of cells with hexyl aminolevulinate (HAL) induced the same amount of
      fluorescence as 5-ALA and methyl aminolevulinate (MAL) at about a 100-fold lower
      concentration. Incubation with HAL-induced accumulation of at least twice as much
      porphyrins in RA- and HS 192.T-cells than 5-ALA and MAL in OA-cells. Similar
      levels of porphyrins were accumulated in RA and the malignant cells. In vivo,
      intra-articular application of 5-ALA induced a significant porphyrin accumulation
      in synovitis tissue as measured by in situ fluorescence spectroscopy. In contrast
      to our in vitro results and other reports, we could not detect enhanced
      fluorescence after application of up to 0.1mg HAL. 

PMID- 25048872
TI  - Extramammary Paget's disease treated with topical and systemic photodynamic
      therapy.
AB  - Surgical excision and radiotherapy for extramammary Paget's disease (EMPD) at
      specific sites such as the groin and genitalia is often inappropriate. An 80-year
      old man with histologically proven EMPD of the left groin and scrotum was
      referred for PDT. The lesion and normal skin thickness were measured by a 20MHz,
      two-dimensional 'B' ultrasound scanner (US). delta-5-Aminolaevulinic acid (ALA),
      was applied followed 6h later by irradiation using a filtered xenon-arc lamp.
      Clinical improvement was apparent four weeks after first PDT session with a
      reduction in ulceration and lesion size and moderate thickness reduction on US.
      Superficial ulceration recurred 9 months after the fifth treatment. This
      recurrence was treated with intravenously administered porfimer sodium. This,
      followed by one topical PDT treatment resulted in significant clinical and US
      cure and the patient remains disease free at 1-year follow-up. 

PMID- 25048873
TI  - Leeds in may.

PMID- 25048874
TI  - Myeloid neoplasms after breast cancer: "therapy-related" not an independent poor
      prognostic factor.
AB  - Two hundred and thirty-five consecutive patients presenting to a single center
      with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after breast
      cancer treatment were compared with matched patients with de novo AML or MDS.
      There was no significant difference in median overall survival (OS) times between
      patients with therapy-related AML and those with de novo AML (8.7 months vs.10.2
      months; p = 0.17). Patients with therapy-related MDS had slightly lower median
      baseline platelet counts and a higher frequency of poor cytogenetics than those
      with de novo MDS, but the two groups had similar OS times (13.6 months vs. 18.9
      months; p = 0.06). Multivariate analysis revealed that cytogenetic risk, baseline
      white blood cell count, age and performance status were predictive for OS time in
      AML and that cytogenetic risk and performance status were predictive for OS time
      in MDS. Having therapy-related disease is not an independent risk factor in
      patients with myeloid neoplasms and with a history of breast cancer. Clinical
      trials should be designed to serve both populations. 

PMID- 25048875
TI  - Impact of the perioperative neutrophil-to-lymphocyte ratio on the long-term
      survival following an elective resection of colorectal carcinoma.
AB  - PURPOSES: The present study was designed to evaluate the prognostic value of the
      perioperative neutrophil-to-lymphocyte ratio (NLR) for the long-term survival in
      patients with colorectal cancer. METHODS: This was a retrospective study of 524
      patients with histologically proven stage II or III colorectal cancer who
      underwent curative colorectal resection. We classified patients into a low NLR
      group or high NLR group base on their NLR values at three time points (before
      surgery (Pre), on the first postoperative day (POD1), and on the third or fourth
      postoperative day (POD3)) and evaluated the survival according to the group.
      RESULTS: The cancer-specific survival was significantly longer in the groups with
      a low NLR on POD3. The disease-free survival was significantly longer in the
      group with a low NLR on Pre. We subsequently allocated a score of 1 to patients
      with a high NLR at each point and reclassified patients into those with a low
      perioperative NLR group (score of 0 or 1) and high perioperative NLR group (score
      of 2 or 3). Both the cancer-specific survival and disease-free survival rates
      were significantly different between the two perioperative NLR groups. Both
      univariate and multivariate analyses demonstrated that being in the high
      perioperative NLR group was an independent risk factor for both the cancer
      specific survival and disease-free survival. CONCLUSIONS: Not only the
      preoperative but also the postoperative NTR is thus considered to be a predictor
      of the long-time survival in patients with colorectal cancer.

PMID- 25048876
TI  - Brief report: erosions and sclerosis on radiographs precede the subsequent
      development of syndesmophytes at the same site: a twelve-year prospective
      followup of patients with ankylosing spondylitis.
AB  - OBJECTIVE: To analyze whether erosions, sclerosis, and squaring assessed on
      radiographs precede the development of syndesmophytes in patients with ankylosing
      spondylitis (AS). METHODS: Patients with AS from the Outcome in Ankylosing
      Spondylitis International Study (OASIS) cohort were followed up for 12 years,
      with radiographs obtained every 2 years. Two readers (reader 1 and reader 2)
      scored radiographs according to the modified Stoke Ankylosing Spondylitis Spine
      Score (mSASSS) and recorded abnormalities per vertebral corner. Progression from
      erosions, sclerosis, or squaring to (bridging) syndesmophytes was investigated
      using multilevel longitudinal (autoregressive and time-lagged) regression
      analysis. Interactions with reader and spinal region were investigated. RESULTS:
      The analysis included 211 patients (71% male, 85% HLA-B27 positive) with a mean
      +/- SD age of 43 +/- 13 years and a symptom duration of 21 +/- 12 years. A total
      of 921 radiographs were included, with 20,509 (reader 1) and 20,568 (reader 2)
      vertebral corners evaluable. Erosions were found in 1% and 2.5%, sclerosis in
      0.3% and 1.7%, squaring in 6.5% and 5.1%, and syndesmophytes in 25% and 27%, by
      reader 1 and reader 2, respectively. The odds ratio for a new syndesmophyte to
      occur within 2 years at the same vertebral corner if erosions, sclerosis, or
      squaring were present was 2.0 (95% confidence interval [95% CI] 1.7-2.3) for the
      cervical and lumbar spine together, 3.1 (95% CI 2.5-3.9) for the cervical spine,
      and 1.3 (95% CI 1.0-1.6) for the lumbar spine. When vertebral corners with
      erosions, sclerosis, and squaring were analyzed separately, this effect was
      statistically significant for erosions and for sclerosis, but not for squaring.
      CONCLUSION: Erosions and sclerosis occur infrequently in patients with AS, but
      when they do occur, they precede the development of a new syndesmophyte, and are
      therefore important to assess.

PMID- 25048877
TI  - Alteration of vascular reactivity in heart failure: role of phosphodiesterases 3
      and 4.
AB  - BACKGROUND AND PURPOSE: This study examined the role of the main vascular cAMP
      hydrolysing phosphodiesterases (cAMP-PDE) in the regulation of basal vascular
      tone and relaxation of rat aorta mediated by beta-adrenoceptors, following heart
      failure (HF). EXPERIMENTAL APPROACH: Twenty-two weeks after proximal aortic
      stenosis, to induce HF, or SHAM surgery in rats, we evaluated the expression,
      activity and function of cAMP-PDE in the descending thoracic aorta. KEY RESULTS:
      HF rat aortas exhibited signs of endothelial dysfunction, with alterations of the
      NO pathway, and alteration of PDE3 and PDE4 subtype expression, without changing
      total aortic cAMP-hydrolytic activity and PDE1, PDE3 and PDE4 activities.
      Vascular reactivity experiments using PDE inhibitors showed that PDE3 and PDE4
      controlled the level of PGF2alpha -stimulated contraction in SHAM aorta. PDE3
      function was partially inhibited by endothelial NO, whereas PDE4 function
      required a functional endothelium and was under the negative control of PDE3. In
      HF, PDE3 function was preserved, but its regulation by endothelial NO was
      altered. PDE4 function was abolished and restored by PDE3 inhibition. In
      PGF2alpha -precontracted arteries, beta-adrenoceptor stimulation-induced
      relaxation in SHAM aorta, which was abolished in the absence of functional
      endothelium, as well as in HF aortas, but restored after PDE3 inhibition in all
      unresponsive arteries. CONCLUSIONS AND IMPLICATIONS: Our study underlines the key
      role of the endothelium in controlling the contribution of smooth muscle PDE to
      contractile function. In HF, endothelial dysfunction had a major effect on PDE3
      function and PDE3 inhibition restored a functional relaxation to beta
      adrenoceptor stimulation.

PMID- 25048878
TI  - Synergic effects of artemisinin and resveratrol in cancer cells.
AB  - PURPOSE: The aim of this study was to investigate whether resveratrol (Res)
      combined with artemisinin (ART) possess synergistic effect on different cancer
      cells. MATERIALS AND METHODS: The viability of HepG2 and HeLa cells treated with
      ART and Res was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Combination index (CI) analysis and isobologram were used to
      assess the synergistic effect of ART and Res in different ratios. Wound-healing
      assay was used to investigate the migration rate. AO staining and fluorescent
      microscopy measurements were performed to detect the cell apoptosis. Reactive
      oxygen species (ROS) was measured with 2'7'-dichlorofluorescein diacetate (DCFH
      DA). RESULTS: MTT assay indicated that ART and Res inhibited the growth of HeLa
      and HepG2 cells in a dose-dependent manner. The combination of ART and Res
      exhibited the strongest anticancer effect at the ratio of 1:2 (ART to Res). The
      combination of the two drugs also markedly reduced the ability of cell migration.
      Apoptosis analysis showed that combination of ART and Res significantly increased
      the apoptosis and necrosis rather than use singly. Additionally, ROS levels were
      elevated by combining ART with Res. CONCLUSIONS: Taken together, the present
      study suggested that ART and Res possessed the synergistic anti-tumor effect. ART
      in combination with Res could be an effective therapeutic strategy for cancer.

PMID- 25048879
TI  - Mechanistic investigation of the bypass of a bulky aromatic DNA adduct catalyzed
      by a Y-family DNA polymerase.
AB  - 3-Nitrobenzanthrone (3-NBA), a nitropolyaromatic hydrocarbon (NitroPAH) pollutant
      in diesel exhaust, is a potent mutagen and carcinogen. After metabolic
      activation, the primary metabolites of 3-NBA react with DNA to form dG and dA
      adducts. One of the three major adducts identified is N-(2'-deoxyguanosin-8-yl)-3
      aminobenzanthrone (dG(C8-N-ABA)). This bulky adduct likely stalls replicative DNA
      polymerases but can be traversed by lesion bypass polymerases in vivo. Here, we
      employed running start assays to show that a site-specifically placed dG(C8-N
      ABA) is bypassed in vitro by Sulfolobus solfataricus DNA polymerase IV (Dpo4), a
      model Y-family DNA polymerase. However, the nucleotide incorporation rate of Dpo4
      was significantly reduced opposite both the lesion and the template position
      immediately downstream from the lesion site, leading to two strong pause sites.
      To investigate the kinetic effect of dG(C8-N-ABA) on polymerization, we utilized
      pre-steady-state kinetic methods to determine the kinetic parameters for
      individual nucleotide incorporations upstream, opposite, and downstream from the
      dG(C8-N-ABA) lesion. Relative to the replication of the corresponding undamaged
      DNA template, both nucleotide incorporation efficiency and fidelity of Dpo4 were
      considerably decreased during dG(C8-N-ABA) lesion bypass and the subsequent
      extension step. The lower nucleotide incorporation efficiency caused by the
      lesion is a result of a significantly reduced dNTP incorporation rate constant
      and modestly weaker dNTP binding affinity. At both pause sites, nucleotide
      incorporation followed biphasic kinetics with a fast and a slow phase and their
      rates varied with nucleotide concentration. In contrast, only the fast phase was
      observed with undamaged DNA. A kinetic mechanism was proposed for the bypass of
      dG(C8-N-ABA) bypass catalyzed by Dpo4. 

PMID- 25048880
TI  - Whole-body total lesion glycolysis measured on fluorodeoxyglucose positron
      emission tomography/computed tomography as a prognostic variable in metastatic
      breast cancer.
AB  - BACKGROUND: In this retrospective study, the authors evaluated the prognostic
      value of whole-body total lesion glycolysis (WTLG) on FDG/PET images in
      metastatic breast cancer (MBC) patients. METHODS: We retrospectively evaluated 54
      MBC patients who were diagnosed as having one or more metastatic lesions between
      June 2005 and March 2013. Twenty-four patients were diagnosed at the initial
      presentation (group A) and 30 patients were diagnosed for the first time at some
      point after a surgery (group B). Patients were excluded if they had received
      chemotherapy within 30 days before PET/CT. SUVmax and total TLG were calculated
      for all lesions in each patient and the highest SUVmax and the whole-body TLG
      (WTLG) values were used as independent variables for the analyses. Mean ages and
      the proportions of histopathological subtypes were compared between two groups
      using Mann-Whitney U test and Fisher's exact test, respectively. The prognostic
      significance of PET parameters was assessed using Cox proportional hazards
      regression analysis. RESULTS: For groups A and B, the median follow-up period was
      26 months (range, 3-58 months) and 40.5 months (range, 3-69 months), and the
      median age was 61 years (range, 42-81 years) and 59 years (range, 24-74 years),
      respectively. There were no significant differences between two groups in age (p
      = 0.294) or histopathological subtype (p = 0.384). In the univariate analyses,
      WTLG was found to be significantly associated with overall survival (OS) for
      patients of group A (p = 0.012). In the multivariate analysis, WTLG was also
      significantly associated with OS (p = 0.015). Only hormonal receptor level was a
      significant indicator of longer OS in patients with recurrent MBC (group B).
      CONCLUSIONS: This study demonstrated that WTLG on PET/CT is an independent
      prognostic factor for survival in breast cancer patients with metastases at the
      initial presentation.

PMID- 25048881
TI  - Metagenomic profiles and antibiotic resistance genes in gut microbiota of mice
      exposed to arsenic and iron.
AB  - Iron (Fe) has been widely applied to treat arsenic (As)-contaminated water, and
      Fe could influence bioavailability and toxicity of As. However, little is known
      about the impact of As and/or Fe on gut microbiota, which plays important roles
      in host health. In this study, high-throughput sequencing and quantitative real
      time PCR were applied to analyze the impact of As and Fe on mouse gut microbiota.
      Co-exposure of As and Fe mitigated effects on microbial community to a certain
      extent. Correlation analysis showed the shifts in gut microbiota caused by As
      and/or Fe exposure might be important reason of changes in metabolic profiles of
      mouse. For antibiotic resistance genes (ARGs), co-exposure of As and Fe increased
      types and abundance of ARGs. But for high abundance ARGs, such as tetQ, tetO and
      tetM, co-exposure of As and Fe mitigated effects on their abundances compared to
      exposure to As and Fe alone. No obvious relationship between ARGs and mobile
      genetic elements were found. The changes in ARGs caused by metal exposure might
      be due to the alteration of gut microbial diversity. Our results show that
      changes of gut microbial community caused by As and/or Fe can influence host
      metabolisms and abundances of ARGs in gut, indicating that changes of gut
      microbiota should be considered during the risk assessment of As and/or Fe. 

PMID- 25048882
TI  - Deformities of chironomid larvae and heavy metal pollution: from laboratory to
      field studies.
AB  - Mouthpart deformities of Chironomus riparius larvae (Diptera) have been
      investigated to evaluate the toxic effects of contamination by heavy metals in
      the Genna Stream (Central Italy), situated in an area subjected to intensive
      swine farms (40000 heads). The livestock farming (fertirrigation) contributes to
      metal pollution of the Genna Stream with an increase of copper, zinc, cadmium,
      chromium and nickel in the sediments of the downstream stations. The incidence of
      mentum deformities was very high at all sampling stations, about 56%. The highest
      values of deformities were found in the intermediate river reach (St. 3: 65%) and
      in March (66%), mainly due to an increase in severe deformities. The high
      incidence of severe deformities (30%) is attributed to the high pollution level
      by heavy metals in the sediments, in particular to copper and zinc, which showed
      the highest average value at St. 3 and in March. This field study reflected the
      relationships between sediment metal concentrations and chironomid mouthpart
      deformities, previously observed in laboratory tests, and highlighted these
      deformities as toxicity endpoints. This feature paves the way for their use as an
      effective tool in freshwater bioassessment monitoring programs to evaluate the
      toxic effects of metal contamination in freshwater ecosystems. 

PMID- 25048883
TI  - Environmental effects and fate of the insecticide bifenthrin in a salt-marsh
      mesocosm.
AB  - Bifenthrin is a widely used synthetic pyrethroid insecticide that is often
      applied to crops, turf, and residential structures for the control of insects.
      Like other insecticides, bifenthrin has the potential to contaminate bodies of
      water that are adjacent to the application site via spray drift and runoff during
      storm events. The objective of this study was to examine the lethal and sublethal
      effects of bifenthrin on grass shrimp, Palaemonetes pugio, and sheepshead minnow,
      Cyprinodon variegatus in a 28 d mesocosm experiment under estuarine conditions.
      Endpoints included mortality and growth and the oxidative stress biomarkers of
      lipid peroxidation, glutathione, and catalase. In the mesocosm experiment, 24 h
      and 96 h caged shrimp LC50s were 0.061 and 0.051 MUg L(-1), respectively. The
      uncaged grass shrimp 28 d LC50 was 0.062 MUg L(-1). Fifty percent mortality was
      not reached in the uncaged sheepshead minnow. Bifenthrin did not have a
      significant effect on the growth of the shrimp, but there was an increasing
      impact on fish growth. However, it is uncertain as to whether this pattern is a
      direct effect of the chemical or if it is due to increased food availability
      resulting from mortality in prey species. The oxidative stress assays were
      largely inconclusive. Bifenthrin was eliminated rapidly from the water column and
      readily partitioned to sediments. The LC50s for adult and larval P. pugio were
      below published Estimated Environmental Concentration (EEC) values and were
      within the range of bifenthrin concentrations that have been measured in rivers,
      channels, and creeks.

PMID- 25048884
TI  - Development of Comparative Toxicity Potentials of 14 cationic metals in
      freshwater.
AB  - Site-dependent and site-generic Comparative Toxicity Potentials (CTPs) (also
      known as Characterization Factors (CFs)) were calculated for 14 cationic metals
      (Al(III), Ba, Be, Cd, Co, Cr(III), Cs, Cu(II), Fe(II), Fe(III), Mn(II), Ni, Pb,
      Sr and Zn), to be applied in Life Cycle Impact Assessment. CTPs were calculated
      for 7 EU-archetypes, taking bioavailability and speciation pattern into account.
      The resulting site-dependent CTPs showed up to 2.4-6.5 orders of magnitude
      variation across archetypes for those metals that form stable hydroxyl compounds
      in slightly alkaline waters (Al(III), Be, Cr(III), Cu(II) and Fe(III)),
      emphasizing the importance of using site-dependent CTPs for these metals where
      possible. For the other metals, CTPs stayed within around 0.9 orders of
      magnitude, making spatial differentiation less important. In acidic waters
      (pH<6.4), Al(III) and Cu(II) had the highest CTPs, while Cd ranked highest in
      other waters. Based on the site-dependent CTPs, site-generic CTPs were developed
      applying different averaging principle. Emission weighted average of 7 EU
      archetype CTPs was recommended as site-generic CTP for use in LCA studies, where
      receiving location is unclear. Compared to previous studies by Gandhi et al.
      (2010, 2011a), new site-dependent CTPs were similar or slightly higher for Cd,
      Co, Ni, Pb and Zn, but 1-2 orders of magnitude higher for Cu. Compared to the
      default site-generic CTPs in the frequently used characterization models USES-LCA
      and USEtox, new site-generic CTPs were mostly higher or similar, within up to ~2
      orders of magnitude difference. 

PMID- 25048885
TI  - 6:2 Fluorotelomer iodide in vitro metabolism by rat liver microsomes: comparison
      with [1,2-(14)C] 6:2 fluorotelomer alcohol.
AB  - 6:2 Fluorotelomer iodide [6:2 FTI, F(CF2)6CH2CH2I] is the industrial raw material
      used to manufacture 6:2 fluorotelomer alcohol [6:2 FTOH, F(CF2)6CH2CH2OH] and 6:2
      FTOH-based products. During its manufacture and industrial use, workers may be
      exposed to via oral, dermal or inhalation of 6:2 FTI. Therefore it is useful to
      understand how 6:2 FTI may be metabolized and into what transformation products.
      6:2 FTI in vitro rat liver microsomal metabolism was explored for the first time
      to compare its biotransformation potential with that of [1,2-(14)C] 6:2 FTOH
      [F(CF2)6(14)CH2(14)CH2OH]. 6:2 FTI and 6:2 FTOH metabolite yields were determined
      in closed-bottle systems using Sprague Dawley and Wistar Han rat microsomes after
      incubation at 37  degrees C for up to 6h with NADPH (reduced form of nicotinamide
      adenine dinucleotide phosphate)-addition and NADPH-regenerating systems,
      respectively. 5:3 acid [F(CF2)5CH2CH2COOH] was the most abundant metabolite for
      6:2 FTI (3.3-6.3 mol%) and 6:2 FTOH (9-12 mol%). Perfluorobutanoic acid (PFBA),
      perfluoropentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA) in sum
      accounted for 1.3-2.2 mol% from 6:2 FTI and 2.7-4.4 mol% from 6:2 FTOH
      biotransformation. Perfluoroheptanoic acid (PFHpA) accounted for 0.14-0.36 mol%
      from 6:2 FTI but only 0.01-0.06 mol% from 6:2 FTOH biotransformation. These
      results suggest that mammalian systems exposed to 6:2 FTI or 6:2 FTOH would form
      5:3 acid, PFBA, PFPeA, PFHxA as the primary stable metabolites, whereas more
      PFHpA would be expected from 6:2 FTI biotransformation.

PMID- 25048886
TI  - Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin,
      but not to fat mass or fat distribution in humans.
AB  - OBJECTIVE: Since bisphenol A (BPA) has been shown to induce obesity in
      experimental studies, we explored the associations between BPA and fat mass, fat
      distribution and circulating levels of adiponectin, leptin and ghrelin in humans.
      METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors
      (PIVUS), fat mass and fat distribution were determined in 70-year-old men and
      women (n=890) by dual-energy X-ray absorptiometry (DXA) and magnetic resonance
      imaging (MRI) (n=287). Serum levels of BPA were analyzed using isotope liquid
      chromatography/tandem mass spectrometer (API4000LC-MS/MS). Hormone levels were
      analyzed with radioimmunoassays (RIA) or enzyme-linked immunosorbent assay
      (ELISA). Imaging was performed approximately two years following collection of
      other data. RESULTS: Serum concentrations of BPA were not related to adipose
      tissue measurements by DXA or MRI. BPA associated positively with adiponectin and
      leptin, but negatively with ghrelin, following adjustments for sex, height, fat
      mass, lean mass, smoking, alcohol consumption, physical activity, energy intake,
      and educational levels (p<0.001, p=0.009, p<0.001, respectively). The
      relationship between BPA and ghrelin was stronger in women than in men.
      CONCLUSION: Although no relationships between BPA levels and measures of fat mass
      were seen, BPA associated strongly with the adipokines adiponectin and leptin and
      with the gut-hormone ghrelin suggesting that BPA may interfere with hormonal
      control of hunger and satiety.

PMID- 25048887
TI  - Particulate and colloidal silver in sewage effluent and sludge discharged from
      British wastewater treatment plants.
AB  - Differential filtration was used to measure silver (>2 nm) entering and leaving
      nine sewage treatment plants (STPs). The mean concentration of colloidal (2-450
      nm) silver, which includes nanosilver, was found to be 12 ng L(-1) in the
      influent and 6 ng L(-1) in the effluent. For particulate silver (>450 nm) the
      mean values were 3.3 MUg L(-1) for influent and 0.08 MUg L(-1) for effluent.
      Thus, removal was around 50% and 98% for colloidal and particulate silver
      respectively. There was no significant difference in performance between the
      different types of STP investigated (three examples each of activated sludge,
      biological filter and biological filter with tertiary treatment located across
      England, UK). In addition, treated sewage sludge samples (biosolids) were taken
      from several STPs to measure the total silver likely to be discharged to soils.
      Total silver was 3-14 mg kg(-1) DW in the sludge (median 3.6), which if the
      sludge were added at the recommended rate to soil, would add 11 MUg kg(-1) yr(-1)
      to the top 20 cm soil layer. Predicted concentrations using the LF2000-WQX model
      for all the rivers of England and Wales for nanosilver were typically in the 0-1
      ng L(-1) range but levels up to 4 ng L(-1) are possible in a high discharge and
      low flow scenario. Predicted concentrations for the total particulate forms were
      mostly below 50 ng L(-1) except for a high discharge and low flow scenario where
      concentrations could reach 135 ng L(-1).

PMID- 25048888
TI  - Inhibition of selected bacterial growth by three hydrocarbons: mathematical
      evaluation of toxicity using a toxicodynamic equation.
AB  - The individual toxicity of different hydrocarbons (naphthalene, cyclododecane and
      aniline) on the growth of selected bacteria (Pseudomonas sp., Phaeobacter sp. and
      Leuconostoc mesenteroides) was studied by means of a toxicodynamic model
      combination of two sigmoid equations (logistic and Weibull). All the
      toxicological effects on growth parameters and kinetic properties were
      characterized and the global toxicity of such chemicals was evaluated. It was
      observed that two kinetic parameters (maximum growth and maximum growth rate)
      were in almost all cases influenced by the hydrocarbons studied. Aniline was less
      toxic than cyclododecane and naphthalene. The presented approach is a reasonable
      starting point for understanding and modeling complete and real assessment of
      chemical toxic effects on bacterial growths. The values of EC50,tau could be used
      for a most efficient comparison of the individual toxicity of chemicals. 

PMID- 25048889
TI  - Comparison of TiO2 nanoparticle and graphene-TiO2 nanoparticle composite
      phototoxicity to Daphnia magna and Oryzias latipes.
AB  - With a dramatic rise in complexity, needs of nanotoxicology research go beyond
      simple forms of nanomaterials. This study compared the phototoxicity of nano-TiO2
      and graphene-TiO2 nanocomposite (GNP). GNP was synthesized based on a
      hydrothermal method, which simultaneously performed the reduction of graphene
      oxide and nano-TiO2 loading. A series of acute toxicity tests of nano-TiO2,
      graphene and GNP was performed on two aquatic organisms, Daphnia magna and
      Oryzias latipes. Fast and substantial agglomeration and sedimentation of
      nanoparticles in test media and surface attachment of nano-TiO2 and GNP on D.
      magna surface was observed. Similar phototoxicity of nano-TiO2 and GNP for both
      species existed, though compared with nano-TiO2, GNP had a 2.3-fold increase in
      visible light photocatalytic ROS generation. In summary, this study demonstrated
      the significance of illumination spectrum, particle behavior, and species
      sensitivity on nanophototoxicity, and the needs for research on increasingly
      sophisticated functional materials. 

PMID- 25048890
TI  - Synergy between glyphosate- and cypermethrin-based pesticides during acute
      exposures in tadpoles of the common South American toad Rhinella arenarum.
AB  - The herbicide glyphosate and the insecticide cypermethrin are key pesticides of
      modern management in soy and corn cultures. Although these pesticides are likely
      to co-occur in ephemeral ponds or aquatic systems supporting amphibian wildlife,
      the toxicological interactions prevailing in mixtures of these two pesticides
      have been little studied. The current study evaluated the toxicity of equitoxic
      and non-equitoxic binary mixtures of glyphosate- and cypermethrin-based
      pesticides to tadpoles of the common South American toad, Rhinella arenarum. Two
      different combinations of commercial products were tested: glyphosate Glifosato
      Atanor(r)+cypermethrin Xiper(r) and glyphosate Glifoglex(r)+cypermethrin
      Glextrin(r). When tested individually, the formulations presented the following
      96 h-LC50s: Glifosato Atanor(r) 19.4 mg ae L(-1) and Glifoglex 72.8 mg ae L(-1),
      Xiper(r) 6.8 mg L(-1) and Glextrin(r) 30.2 mg L(-1). Equitoxic and non-equitoxic
      mixtures were significantly synergic in both combinations of commercial products
      tested. The magnitude of the synergy (factor by which toxicity differed from
      concentration addition) was constant at around twofold for all tested proportions
      of the glyphosate Glifoglex(r)+cypermethrin Glextrin(r) mixture; whereas the
      magnitude of the synergy varied between 4 and 9 times in the glyphosate Glifosato
      Atanor(r)+cypermethrin Xiper(r) mixture. These results call for more research to
      be promptly undertaken in order to understand the mechanisms behind the synergy
      observed and to identify and quantify the extent of its environmental impacts.

PMID- 25048891
TI  - PAH toxicity at aqueous solubility in the fish embryo test with Danio rerio using
      passive dosing.
AB  - As part of the risk assessment process within REACh, prior to manufacturing and
      distribution of chemical substances their (eco)toxicological impacts have to be
      investigated. The fish embryo toxicity test (FET) with the zebrafish Danio rerio
      has gained a high significance as an in vitro alternative to animal testing in
      (eco)toxicology. However, for hydrophobic organic chemicals it remains a
      technical challenge to ensure constant freely dissolved concentration at the
      maximum exposure level during such biotests. Passive dosing with PDMS silicone
      was thus applied to control the freely dissolved concentration of ten PAHs at
      their saturation level in the FET. The experiments gave repeatable results, with
      the toxicity of the PAHs generally increasing with the maximum chemical
      activities of the PAHs. HPLC analysis confirmed constant exposure at the
      saturation level. In additional experiments, fish embryos without direct contact
      to the silicone surface showed similar mortalities as those exposed with direct
      contact to the silicone. Silicone oil overlaying the water phase as a novel
      passive dosing phase had no observable effects on the development of the fish
      embryos until hatching. This study provides further data to support the close
      relationship between the chemical activity and the toxicity of hydrophobic
      organic compounds. Passive dosing from PDMS silicone enabled reliable toxicity
      testing of (highly) hydrophobic substances at aqueous solubility, providing a
      practical way to control toxicity exactly at the maximum exposure level. This
      approach is therefore expected to be useful as a cost-effective initial screening
      of hydrophobic chemicals for potential adverse effects to freshwater vertebrates.

PMID- 25048892
TI  - Agrichemicals chronically inhibit the cortisol response to stress in fish.
AB  - We studied the stress response of Rhamdia quelen fingerlings at 45, 90, 135 and
      180 d following acute exposure to agrichemicals. Herein, we report the novel
      observation that acute exposure of fingerling-aged fish to a methyl parathion
      based insecticide (MPBI) and to a tebuconazole-based fungicide (TBF) induced
      chronic inhibition of the stress response. In contrast, fish exposed to an
      atrazine-simazine-based herbicide (ASBH) recovered the stress response on day 45,
      and fish exposed to a glyphosate-based herbicide (GBH) did not present stress
      response inhibition. Additionally, fish exposed to MPBI, GBH and ASBH showed
      lower survival rates and attained lower final weights. In the case of TBF, the
      presence of the stressful stimulus more strongly influenced the changes in the
      performance parameters than did the agrichemical exposure itself. An impairment
      of the cortisol response may seriously hamper the adaptive response and the
      ability to promote the necessary metabolic and ionic adjustments to respond to
      environmental stress.

PMID- 25048893
TI  - The interactions between CdSe quantum dots and yeast Saccharomyces cerevisiae:
      adhesion of quantum dots to the cell surface and the protection effect of ZnS
      shell.
AB  - The interactions between quantum dots (QDs) and biological systems have attracted
      increasing attention due to concerns on possible toxicity of the nanoscale
      materials. The biological effects of CdSe QDs and CdSe/ZnS QDs with nearly
      identical hydrodynamic size on Saccharomyces cerevisiae were investigated via
      microcalorimetric, spectroscopic and microscopic methods, demonstrating a toxic
      order CdSe>CdSe/ZnS QDs. CdSe QDs damaged yeast cell wall and reduced the
      mitochondrial membrane potential. Noteworthy, adhesion of QDs to the yeast cell
      surface renders this work a good example of interaction site at cell surface, and
      the epitaxial coating of ZnS could greatly reduce the toxicity of Cd-containing
      QDs. These results will contribute to the safety evaluation of quantum dots, and
      provide valuable information for design of nanomaterials. 

PMID- 25048894
TI  - Degradation pattern and risk assessment of chlorantraniliprole on berseem
      (Trifolium alexandrinum L.) using high performance liquid chromatography.
AB  - The persistence pattern of chlorantraniliprole on berseem leaves and its risk
      assessment for the safety of cattle were studied. QuEChERS method was used for
      the extraction and cleanup of samples and the residues of chlorantraniliprole
      were estimated using high performance liquid chromatography (HPLC) and confirmed
      by Liquid Chromatograph-Mass Spectrometer (LCMS-MS). The dissipation studies on
      berseem were carried out by application of chlorantraniliprole at five different
      dosages i.e. 11.6, 17.1, 23.1, 34.7 and 46.2 g a.i. ha(-1). Average initial
      deposits of chlorantraniliprole were found to be 0.47, 0.61, 0.78, 1.15 and 1.31
      mg kg(-1), respectively. The residues reached below determination limit (BDL) of
      0.01 mg kg(-1) in 5, 7, 7, 10 and 10 days for 11.6, 17.1, 23.1, 34.7 and 46.2 g
      a.i. ha(-1) dosages, respectively. Half-life (t1/2) of chlorantraniliprole on
      berseem was observed to be 0.93, 1.14, 1.06, 1.00 and 1.33 days, respectively, at
      11.6, 17.1, 23.1, 34.7 and 46.2 g a.i. ha(-1). It was found that the theoretical
      maximum residue contributions (TMRC) values reached below maximum permissible
      intake (MPI) on 0 day in berseem samples treated with chlorantraniliprole. These
      studies, therefore suggest that the use of chlorantraniliprole formulation at
      different dosages does not seem to pose any hazards to the consumers and a
      waiting period of one day is suggested to reduce the risk before consumption of
      berseem leaves. These data could provide guidance for the proper and safe use of
      this pesticide on berseem in India.

PMID- 25048895
TI  - Physiological and molecular level effects of silver nanoparticles exposure in
      rice (Oryza sativa L.) seedlings.
AB  - The physiological and molecular level changes of silver nanoparticles (AgNPs)
      exposure were investigated in rice (Oryza sativa L.) seedlings. The seedlings
      were exposed to different concentrations of (0, 0.2, 0.5 and 1 mg L(-1)) AgNPs
      for one week. Significant reduction in root elongation, shoot and root fresh
      weights, total chlorophyll and carotenoids contents were observed. Exposure to
      0.5 and 1 mg L(-1) of AgNPs caused significant increase in hydrogen peroxide
      formation and lipid peroxidation in shoots and roots, increased foliar proline
      accumulation and decreased sugar contents. AgNPs exposure resulted in a dose
      dependant increase in reactive oxygen species generation and also caused
      cytotoxicity as evidenced by increased dihydroethidium, 3'-(p-hydroxyphenyl)
      fluorescein and propidium iodide fluorescence. Tetramethylrhodamine methyl ester
      assay showed decreased mitochondrial membrane potential with increasing
      concentrations of AgNPs exposure in roots. Real Time PCR analysis showed
      differential transcription of genes related to oxidative stress tolerance viz.
      FSD1, MSD1, CSD1, CSD2, CATa, CATb, CATc, APXa and APXb in shoots and roots of
      rice seedlings. The overall results suggest that exposure to AgNPs caused
      significant physiological and molecular level changes, oxidative stress and also
      resulted in the induction oxidative stress tolerance mechanisms in rice
      seedlings.

PMID- 25048896
TI  - Chemometric analysis of ecological toxicants in petrochemical and industrial
      environments.
AB  - The application of chemometrics in the assessment of toxicants, such as heavy
      metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) potentially derived from
      petrochemical activities in the microenvironment, is vital in providing
      safeguards for human health of children and adults residing around petrochemical
      industrial regions. Several multivariate statistical methods are used in
      geosciences and environmental protection studies to classify, identify and group
      prevalent pollutants with regard to exhibited trends. Chemometrics can be applied
      for toxicant source identification, estimation of contaminants contributions to
      the toxicity of sites of interest, the assessment of the integral risk index of
      an area and provision of mitigating measures that limit or eliminate the
      contaminants identified. In this study, the principal component analysis (PCA)
      was used for dimensionality reduction of both organic and inorganic substances
      data in the environment, which are potentially hazardous. The high molecular
      weight (HMW) PAHs correlated positively with stronger impact on the model than
      the lower molecular weight (LMW) PAHs, the total petroleum hydrocarbons (TPHs),
      PAHs and BTEX correlate positively in the F1 vs F2 plot indicating similar source
      contributions of these pollutants in the environmental material. Cu, Cr, Cd, Fe,
      Zn and Pb all show positive correlation in the same space indicating similar
      source of contamination. Analytical processes involving environmental assessment
      data obtained in the Niger Delta area of Nigeria, confirmed the usefulness of
      chemometrics for comprehensive ecological evaluation. 

PMID- 25048897
TI  - Quantitative structure-activity relationship for toxicity of ionic liquids to
      Daphnia magna: aromaticity vs. lipophilicity.
AB  - Water solubility of ionic liquids (ILs) allows their dispersion into aquatic
      systems and raises concerns on their pollutant potential. Again, lipophilicity
      can contribute to the toxicity of ILs due to increased ability of the compounds
      to cross lipoidal bio-membranes. In the present work, we have performed
      statistical model development for toxicity of a set of ionic liquids to Daphnia
      magna, a widely accepted model organism for toxicity testing, using computed
      lipophilicity, atom-type fragment, quantum topological molecular similarity
      (QTMS) and extended topochemical atom (ETA) descriptors. The models have been
      developed and validated in accordance with the Organization for Economic Co
      operation and Development (OECD) guidelines for quantitative structure-activity
      relationships (QSARs). The best partial least squares (PLS) model outperforms the
      previously reported multiple linear regression (MLR) model in statistical quality
      and predictive ability (R(2)=0.955, Q(2)=0.917, Rpred(2)=0.848). In this work,
      the ETA descriptors show importance of branching and aromaticity while the QTMS
      descriptor ellipticity efficiently shows which compounds are influential in the
      data set, with reference to the model. While obvious importance of lipophilicity
      is evident from the models, the best model clearly shows the importance of
      aromaticity suggesting that more lipophilic ILs with less toxicity may be
      designed by avoiding aromaticity, nitrogen atoms and increasing branching in the
      cationic structure. The developed quantitative models are in consonance with the
      recent hypothesis of importance of aromaticity for toxicity of ILs. 

PMID- 25048898
TI  - Degradation of roxarsone in a silt loam soil and its toxicity assessment.
AB  - The land application of poultry or swine litter, containing large amounts of
      roxarsone, causes serious arsenic pollution in soil. Understanding
      biotransformation process of roxarsone and its potential risks favors proper
      disposal of roxarsone-contaminated animal litter, yet remains not achieved. We
      report an experimental study of biotransformation process of roxarsone in a silt
      loam soil under various soil moisture and temperature conditions, and the
      toxicity of roxarsone and its products from degradation. Results showed that soil
      moisture and higher temperature promoted roxarsone degradation, associating with
      emergent pentavalent arsenic. Analysis of fluorescein diacetate (FDA) hydrolysis
      activity revealed that roxarsone does not exert acute toxic on soil microbes.
      With the release of inorganic arsenic, FDA hydrolysis activity was inhibited
      gradually, as evidenced by ecotoxicological assessment using Photobacterium
      leiognathi. The results shade new lights on the dynamic roxarsone
      biotransformation processes in soil, which is important for guiding appropriate
      disposal of poultry or swine litter in the environment. 

PMID- 25048899
TI  - Natural radioactivity in various water samples and radiation dose estimations in
      Bolu province, Turkey.
AB  - The level of natural radioactivity for Bolu province of north-western Turkey was
      assessed in this study. There is no information about radioactivity measurement
      reported in water samples in the Bolu province so far. For this reason, gross
      alpha and beta activities of 55 different water samples collected from tap,
      spring, mineral, river and lake waters in Bolu were determined. The mean activity
      concentrations were 68.11 mBq L(-1), 169.44 mBq L(-1) for gross alpha and beta in
      tap water. For all samples the gross beta activity is always higher than the
      gross alpha activity. All value of the gross alpha were lower than the limit
      value of 500 mBq L(-1) while two spring and one mineral water samples were found
      to have gross beta activity concentrations of greater than 1000 mBq L(-1). The
      associated age-dependent dose from all water ingestion in Bolu was estimated. The
      total dose for adults had an average value exceeds the WHO recommended limit
      value. The risk levels from the direct ingestion of the natural radionuclides in
      tap and mineral water in Bolu were determinated. The mean (210)Po and (228)Ra
      risk the value of tap and mineral waters slightly exceeds what some consider on
      acceptable risk of 10(-4) or less.

PMID- 25048900
TI  - MCLR-induced PP2A inhibition and subsequent Rac1 inactivation and
      hyperphosphorylation of cytoskeleton-associated proteins are involved in
      cytoskeleton rearrangement in SMMC-7721 human liver cancer cell line.
AB  - Cyanobacteria-derived toxin microcystin-LR (MCLR) has been widely investigated in
      its effects on normal cells, there is little information concerning its effects
      on cancer cells. In the present study, the SMMC-7721 human liver cancer cell line
      treated with MCLR was used to investigate the change of PP2A, cytoskeleton
      rearrangement, phosphorylation levels of PP2A substrates that related with
      cytoskeleton stability and explored underlying mechanisms. Here, we confirmed
      that MCLR entered into SMMC-7721 cells, bound to PP2A/C subunit and inhibited the
      activity of PP2A. The upregulation of phosphorylation of the PP2A/C subunit and
      PP2A regulation protein alpha4, as well as the change in the association of
      PP2A/C with alpha4, were responsible for the decrease in PP2A activity. Another
      novel finding is that the rearrangement of filamentous actin and microtubules led
      by MCLR may attribute to the increased phosphorylation of HSP27, VASP and cofilin
      due to PP2A inhibition. As a result of weakened interactions with PP2A and
      alterations in its subcellular localization, Rac1 may contribute to the
      cytoskeletal rearrangement induced by MCLR in SMMC-7721 cells. The current paper
      presents the first report demonstrating the characteristic of PP2A in MCLR
      exposed cancer cells, which were more susceptible to MCLR compared with the
      normal cell lines we previously found, which may be owing to the absence of some
      type of compensatory mechanisms. The hyperphosphorylation of cytoskeleton
      associated proteins and Rac1 inactivation which were induced by inhibition of
      PP2A are shown to be involved in cytoskeleton rearrangement. 

PMID- 25048901
TI  - Endocrine disrupting effects of benzotriazole in rare minnow (Gobiocypris rarus)
      in a sex-dependent manner.
AB  - Benzotriazole (BT), an anticorrosive agent, is widely used in industrial
      applications and household dishwashing agents. Despite its reported toxicity to
      aquatic organisms, little is known about its endocrine disrupting effects. In
      this study, adult Chinese rare minnows (Gobiocypris rarus) were exposed to 0.05,
      0.5, and 5 mg L(-1) BT for 28 d. The pathological damage in liver was associated
      with hypertrophy of the hepatocytes, nuclei pyknosis and vacuolization at 5 mg L(
      1) groups. Additionally, the degeneration of the ovary and the stimulation of
      spermatogenesis were observed at 5 mg L(-1) groups. The plasma 17beta-estradiol
      level was significantly increased in the males but decreased in the females at 5
      mg L(-1) (p<0.05). In the brain, the up-regulation of CYP19B, GnRHs, and LHbeta
      mRNA was detected across all doses (p<0.05). In the gonad, the transcriptional
      levels of StAR, CYP11A, 3betaHSD, CYP17, 17betaHSD, and CYP19A were generally
      decreased in the males at 5 mg L(-1) (p<0.05), whereas these genes, except for
      3betaHSD, were significantly increased in females at all concentrations (p<0.05).
      Moreover, the expression level of VTG in the livers from all exposure groups was
      significantly increased compared with controls (p<0.05). Taken together, our
      results indicate that BT could adversely affect the rare minnows in a sex
      dependent manner.

PMID- 25048902
TI  - Toxicity and bioaccumulation of ethofumesate enantiomers in earthworm Eisenia
      fetida.
AB  - Earthworms represent an important food source for many vertebrates and as a
      result, predators may encounter toxic effects via the food chain from consumption
      of contaminated worms. Therefore, including an assessment of xenobiotic to worms
      in risk assessment procedures is advisable. Here we studied the acute toxicity,
      bioaccumulation and elimination of ethofumesate enantiomers in earthworm, Eisenia
      fetida, in a soil. A slight difference in toxicity to earthworm between two
      enantiomers was found, and the calculated LC50 values for (+)-, rac- and (-)
      ethofumesate were 4.51, 5.93 and 7.98 MUg/cm(2), respectively, indicating that
      the acute toxicity of ethofumesate enantiomers was enantioselective. Earthworm
      can uptake ethofumesate but the bioaccumulation curve did not reach the steady
      state. In the elimination experiment, the concentrations of ethofumesate in
      earthworm declined following a first-order decay model with a short half life of
      1.8d. The bioaccumulation and elimination of ethofumesate in earthworm were both
      nonenantioselective. In combination with other studies, a linear relationship
      between Log BSAFs and Log Kow was observed, and the Log BSAFs increased with
      increasing Log Kow. But the elimination rate did not show any correlation with
      the Kow value.

PMID- 25048903
TI  - Assessment of neurotoxic effects and brain region distribution in rat offspring
      prenatally co-exposed to low doses of BDE-99 and methylmercury.
AB  - Exposure to polybrominated diphenyl ether (PDBE) and methylmercury (MeHg) can
      occur simultaneously as both contaminants are found in the same food sources,
      especially fish, seafood, marine mammals and milk. The aim of this study was to
      assess the effects of exposure to low levels of MeHg (2.0 MUg mL(-1) in drinking
      water) and BDE-99 (0.2 mg kg(-1) d(-1)) from gestational day 6 to postnatal day
      (PND) 21, alone and in combination, on neurobehavioral development and redox
      responses in offspring. The present study demonstrated an interaction due to co
      exposure with low doses of MeHg and BDE-99 enhanced developmental neurotoxic
      effects. These effects were manifested as the delayed appearance of negative
      geotaxis reflexes, impaired motor coordination, and induction of oxidative stress
      in the cerebellum. In particular, the cerebellum may be a sensitive target for
      combined MeHg and BDE-99 toxicity. The neurotoxicity of low dose MeHg was
      exacerbated by the presence of low dose of BDE-99. It is concluded that prenatal
      co-exposure to MeHg and BDE-99 causes oxidative stress in the cerebellum of
      offspring by altering the activity of different antioxidant enzymes and producing
      free radicals. Hg retention was not affected by co-exposure to BDE-99. However,
      MeHg co-exposure seemed to increase BDE-99 concentrations in selected brain
      regions in pups compared to pups exposed to BDE-99 only. These results showed
      that the adverse effects following prenatal co-exposure to MeHg and BDE-99 were
      associated with tissue concentrations very close to the current human body burden
      of this persistent bioaccumulative compound.

PMID- 25048904
TI  - The effects of acrylamide polyelectrolytes on aquatic organisms: relating
      toxicity to chain architecture.
AB  - Understanding the inherent toxicity of water-soluble synthetic polyelectrolytes
      is critical for adequate risk management as well as enhancing product design when
      biological activity is a key performance index (e.g. for application in
      biofouling bivalves' control). The toxicity of two cationic acrylamide copolymers
      with different chain branching degree was evaluated. Standard ecotoxicity tests
      were conducted with microalgae and daphnids. The susceptibility of Corbicula
      fluminea, as a biofouling bivalve, was also evaluated. The effect of
      polyelectrolyte on the test media viscosity and the polymer chain size
      distributions under the experimental conditions were also examined. The
      susceptibility of the microalgae to both polymers was similar. As the complexity
      and size of the test organisms increased, differences in toxicity due to
      different chain architecture were noticeable. The more branched polymer was
      significantly less toxic to both daphnids and the bivalves, which could be linked
      to the distinctive features of its bimodal size chain distribution. This
      architecture resulted in both more compact globular molecules and the formation
      of aggregates, which reduce the polymer interaction with the biological surfaces.
      The results of this study promote the incorporation of environmental
      considerations in polyelectrolyte development and contribute to the design of
      improved solutions for controlling biofouling bivalves. 

PMID- 25048905
TI  - Pollution-induced community tolerance to non-steroidal anti-inflammatory drugs
      (NSAIDs) in fluvial biofilm communities affected by WWTP effluents.
AB  - We assessed the tolerance acquired by stream biofilms to two non-steroidal anti
      inflammatory-drugs (NSAIDs), ibuprofen and diclofenac. Biofilms came from a
      stream system receiving the effluent of a wastewater treatment plant (WWTP). The
      response of biofilms from a non-polluted site (upstream the WWTP) was compared to
      that of others downstream with relevant and decreasing levels of NSAIDs.
      Experiments performed in the laboratory following the pollution-induced community
      tolerance (PICT) approach determined that both algae and microbial communities
      from biofilms of the sites exposed at the highest concentrations of ibuprofen and
      diclofenac acquired tolerance to the mixture of these NSAIDs occurring at the
      sites. It was also observed that the chronic pollution by the WWTP effluent
      affected the microbial metabolic profile, as well as the structure of the algal
      community. The low (at ng L(-1) level) but chronic inputs of pharmaceuticals to
      the river ecosystem result in tolerant communities of lower diversity and altered
      microbial metabolism.

PMID- 25048906
TI  - Resistance and resilience responses of a range of soil eukaryote and bacterial
      taxa to fungicide application.
AB  - The application of plant protection products has the potential to significantly
      affect soil microbial community structure and function. However, the extent to
      which soil microbial communities from different trophic levels exhibit resistance
      and resilience to such compounds remains poorly understood. The resistance and
      resilience responses of a range of microbial communities (bacteria, fungi,
      archaea, pseudomonads, and nematodes) to different concentrations of the
      strobilurin fungicide, azoxystrobin were studied. A significant concentration
      dependent decrease, and subsequent recovery in soil dehydrogenase activity was
      recorded, but no significant impact on total microbial biomass was observed.
      Impacts on specific microbial communities were studied using small subunit (SSU)
      rRNA terminal restriction fragment length polymorphism (T-RFLP) profiling using
      soil DNA and RNA. The application of azoxystrobin significantly affected fungal
      and nematode community structure and diversity but had no impact on other
      communities. Community impacts were more pronounced in the RNA-derived T-RFLP
      profiles than in the DNA-derived profiles. qPCR confirmed that azoxystrobin
      application significantly reduced fungal, but not bacterial, SSU rRNA gene copy
      number. Azoxystrobin application reduced the prevalence of ascomycete fungi, but
      increased the relative abundance of zygomycetes. Azoxystrobin amendment also
      reduced the relative abundance of nematodes in the order Enoplia, but stimulated
      a large increase in the relative abundance of nematodes from the order
      Araeolaimida. 

PMID- 25048907
TI  - Bioavailability and pharmacokinetics of arsenic are influenced by the presence of
      cadmium.
AB  - Mine wastes contain a mixture of metals and metalloids including arsenic (As) and
      cadmium (Cd). This study investigated the potential interaction between As and Cd
      in a rat model. Sprague Dawley rats were dosed with sodium arsenate via the oral
      (0, 0.5, 5 and 15 mg As kg(-1) b.w.) or intravenous (0.5 mg As kg(-1) b.w.) route
      to establish its dose-response relationship in terms of bioavailability and
      pharmacokinetic parameters. Bioavailability of As reduced when the dose of As
      increased. For the interaction study a fixed oral dose of As at 2.5 mg As kg(-1)
      b.w. solo and in combination with Cd as cadmium chloride at 3 or 6 mg Cd kg(-1)
      b.w. were administered to rats. Bioavailability of As was decreased by 34-35% in
      the presence of Cd. Elimination half-life of As was also decreased from 69 days
      in the As solo group to 13-22 days in the presence of 3 and 6 mg Cd kg(-1) b.w.
      respectively. Decreased urinary excretion of As and tissue accumulation were also
      observed. A probable explanation for these findings is that As co-administration
      with Cd could have resulted in the formation of less soluble cadmium-arsenic
      complexes in the guts of the rats. Nevertheless, such an interaction between As
      and Cd could only explained about 44-48% of the variation when mine waste
      materials containing both of these elements were administered to rats. This
      suggests other physical properties and chemical compound formation could
      contribute to the observed bioavailability of arsenic in complex environmental
      samples.

PMID- 25048908
TI  - PM10 size distribution of metals and environmental-sanitary risk analysis in the
      city of Torino.
AB  - The mechanisms responsible for negative biological effects due to airborne
      particulate matter (PM) exposure are still being studied, however the
      interactions between metals and biologic systems seem to be of primary
      importance. The aim of the study was to estimate a healthy risk linked to
      exposure to airborne PM10 metals by means of an environmental-sanitary risk
      assessment. Metals PM10 size distribution analysis was carried out in a central
      site of Torino city - Italy, then the Target Hazard Quotient (THQ) and the Cancer
      Risk (CR) were applied, according to standard EPA methods. All sampled metals
      were present on the different PM10 fractions, however some metals were
      distributed in some specific fractions: ANOVA test shows Cr, Cu, Mo and Pb as
      differently distributed among the eight fractions, rising the hypothesis of
      potential effects in specific tracts of respiratory system. Regarding the risk
      assessment, in general the CR was higher for an adult than for a child,
      conversely the THQ resulted higher for a child. While the concentrations of all
      the sampled metals appeared to be under control, their presence in the different
      PM10 fractions and their THQ and CR provided indications related to the body
      districts potentially in contact with these substances. 

PMID- 25048909
TI  - Mycorrhizal fungi modulate phytochemical production and antioxidant activity of
      Cichorium intybus L. (Asteraceae) under metal toxicity.
AB  - Cichorium intybus (common chicory), a perennial plant, common in anthropogenic
      sites, has been the object of a multitude of studies in recent years due to its
      high content of antioxidants utilized in pharmacy and food industry. Here, the
      role of arbuscular mycorrhizal fungi (AMF) in the biosynthesis of plant secondary
      metabolites and the activity of enzymatic antioxidants under toxic metal stress
      was studied. Plants inoculated with Rhizophagus irregularis and non-inoculated
      were grown on non-polluted and toxic metal enriched substrata. The results
      presented here indicate that AMF improves chicory fitness. Fresh and dry weight
      was found to be severely affected by the fungi and heavy metals. The
      concentration of hydroxycinnamates was increased in the shoots of mycorrhizal
      plants cultivated on non-polluted substrata, but no differences were found in
      plants cultivated on metal enriched substrata. The activity of SOD and H2O2
      removing enzymes CAT and POX was elevated in the shoots of mycorrhizal plants
      regardless of the cultivation environment. Photochemical efficiency of inoculated
      chicory was significantly improved. Our results indicate that R. irregularis
      inoculation had a beneficial role in sustaining the plants ability to cope with
      the deleterious effects of metal toxicity. 

PMID- 25048910
TI  - Comparative hepatic in vitro depletion and metabolite formation of major
      perfluorooctane sulfonate precursors in Arctic polar bear, beluga whale, and
      ringed seal.
AB  - Perfluorooctane sulfonate (PFOS) has been reported to be among the most
      concentrated persistent organic pollutants in Arctic marine wildlife. The present
      study examined the in vitro depletion of major PFOS precursors, N-ethyl
      perfluorooctane sulfonamide (N-EtFOSA) and perfluorooctane sulfonamide (FOSA), as
      well as metabolite formation using an assay based on enzymatically viable liver
      microsomes for three top Arctic marine mammalian predators, polar bear (Ursus
      maritimus), beluga whale (Delphinapterus leucas), and ringed seal (Pusa hispida),
      and in laboratory rat (Rattus rattus) serving as a general mammalian model and
      positive control. Rat assays showed that N-EtFOSA (38 nM or 150 ng mL(-1)) to
      FOSA metabolism was >90% complete after 10 min, and at a rate of 23 pmol min(-1)
      mg(-1) protein. Examining all species in a full 90 min incubation assay, there
      was >95% N-EtFOSA depletion for the rat active control and polar bear microsomes,
      ~65% for ringed seals, and negligible depletion of N-EtFOSA for beluga whale.
      Concomitantly, the corresponding in vitro formation of FOSA from N-EtFOSA was
      also quantitatively rat~polar bear>ringed seal>>>beluga whale. A lack of
      enzymatic ability and/or a rate too slow to be detected likely explains the lack
      of N-EtFOSA to FOSA transformation for beluga whale. In the same assays, the
      depletion of the FOSA metabolite was insignificant (p>0.01) and with no
      concomitant formation of PFOS metabolite. This suggests that, in part, a source
      of FOSA is the biotransformation of accumulated N-EtFOSA in free-ranging Arctic
      ringed seal and polar bear.

PMID- 25048911
TI  - Assessment of the Zn-Co mixtures rhizotoxicity under Ca deficiency: using two
      conventional mixture models based on the cell membrane surface potential.
AB  - Toxicity assessment of Zn-Co mixtures involves multiple ions interactions. The
      negative potential (psi0) at the cell membrane surface (CMs) concentrated
      cationic toxicants (denoted {M(2+)}0) and influenced the rhizotoxicity of Co(2+)
      or Zn(2+). The single and joint rhizotoxicity of Co(2+) and Zn(2+) to wheat
      (Triticum aestivum L.) were examined, coupled with different Ca(2+) levels. Joint
      effects of Zn(2+), Co(2+) and Ca(2+) were estimated by the linearly extended
      concentration addition (CA) and response addition (RA) models. Incorporation of
      Ca(2+) in single metal toxicity assessment significantly enhanced the prediction
      accuracy (r(2) increased from 0.948 to 0.550 for Zn(2+) and from 0.903 to 0.611
      for Co(2+), respectively). psi0 affected the multiple metals toxicity in both
      conventional mixture models (r(2)=0.814 for CA model and 0.820 for RA model).
      Concretely, {Zn(2+)}0 alleviated the toxicity of {Co(2+)}0, while {Co(2+)}0 had
      non-significant effect on {Zn(2+)}0 toxicity. Growth responses to {Ca(2+)}0 were
      substantially affected by {Zn(2+)}0 and {Co(2+)}0. Ca addition in medium
      decreased the {M(2+)}0 by reducing the psi0 negativity, moreover this addition
      alleviated Ca deficiency at CMs induced by Zn(2+) (or Co(2+)). These consistent
      results from both extended CA and RA models indicated that psi0 provided a novel
      sight for understanding the rhizotoxicity of multiple metals. 

PMID- 25048912
TI  - Differentiation of PC12 cells expressing estrogen receptor alpha: a new bioassay
      for endocrine-disrupting chemicals evaluation.
AB  - Xeno-estrogens, a class of endocrine disrupting chemicals (EDCs), can disturb
      estrogen receptor-dependent pathways involved in differentiation, proliferation
      or protection. Multiple methods have been developed to characterize the
      disturbances induced by EDCs in different cells or organs. In this study we have
      developed a new tool for the assessment of estrogenic compounds on
      differentiation. For this purpose we used the global model of NGF-induced neurite
      outgrowth of a pseudoneuronal PC12 cell line stably transfected with estrogen
      receptor alpha (PC12 ER). This new test evidences a new selectivity in which
      estradiol, genistein and 4-hydroxytamoxifen increased the NGF-induced neurite
      outgrowth of PC12 ER cells in a dose-dependent manner. In contrast, the strong
      estrogen agonist 17alpha-ethynylestradiol, the strong antagonist raloxifene and
      the agonist bisphenol A were unable to modify the neuritogenesis of PC12 ER
      cells. Therefore, the analysis of neuritogenesis in PC12 ER cells constitutes a
      complementary tool for the characterization of xeno-estrogen activity and also
      serves as a basis for further studies focusing on the mechanisms of EDCs in a
      neuronal context. Moreover, this test constitutes an alternative to animal
      testing. 

PMID- 25048913
TI  - Molecular control of arsenite-induced apoptosis in Caenorhabditis elegans: roles
      of insulin-like growth factor-1 signaling pathway.
AB  - Apoptosis is one of the main cellular processes in responses to arsenic, the well
      known environmental carcinogen. By using the nematode Caenorhabditis elegans as
      an in vivo model, we found that insulin-like growth factor-1 networks and their
      target protein DAF-16/FOXO, known as key regulators of energy metabolism and
      growth, played important roles in arsenite-induced apoptosis. Inactivation of DAF
      2, AGE-1 and AKT-1 caused worms more susceptible to arsenite-induced apoptosis,
      which could be attenuated by DAF-16 knockout. Worms with inactivated AKT-2 and
      SGK-1 or with constitutively activated PDK-1 and AKT-1 showed low levels of
      apoptosis, which could be elevated by DAF-16 mutation. Our results demonstrated
      that DAF-2/IGF-1R, AGE-1/PI3K, PDK-1/PDK1 and AKT-1/PKB negatively regulated the
      arsenite-induced apoptosis, whereas AKT-2 and SGK-1 acted proapoptotically. DAF
      16/FOXO antagonized IGF-1 signals in signaling the arsenite-induced apoptosis,
      and apoptosis promoted by DAF-16 inactivation was attributed to its higher
      sensitivity to oxidative stress. 

PMID- 25048914
TI  - Emerging risks from ballast water treatment: the run-up to the International
      Ballast Water Management Convention.
AB  - Uptake and discharge of ballast water by ocean-going ships contribute to the
      worldwide spread of aquatic invasive species, with negative impacts on the
      environment, economies, and public health. The International Ballast Water
      Management Convention aims at a global answer. The agreed standards for ballast
      water discharge will require ballast water treatment. Systems based on various
      physical and/or chemical methods were developed for on-board installation and
      approved by the International Maritime Organization. Most common are combinations
      of high-performance filters with oxidizing chemicals or UV radiation. A well
      known problem of oxidative water treatment is the formation of disinfection by
      products, many of which show genotoxicity, carcinogenicity, or other long-term
      toxicity. In natural biota, genetic damages can affect reproductive success and
      ultimately impact biodiversity. The future exposure towards chemicals from
      ballast water treatment can only be estimated, based on land-based testing of
      treatment systems, mathematical models, and exposure scenarios. Systematic
      studies on the chemistry of oxidants in seawater are lacking, as are data about
      the background levels of disinfection by-products in the oceans and strategies
      for monitoring future developments. The international approval procedure of
      ballast water treatment systems compares the estimated exposure levels of
      individual substances with their experimental toxicity. While well established in
      many substance regulations, this approach is also criticised for its
      simplification, which may disregard critical aspects such as multiple exposures
      and long-term sub-lethal effects. Moreover, a truly holistic sustainability
      assessment would need to take into account factors beyond chemical hazards, e.g.
      energy consumption, air pollution or waste generation. 

PMID- 25048915
TI  - Distribution and ecological risk of antibiotics in a typical effluent-receiving
      river (Wangyang River) in north China.
AB  - In this study, the occurrence and distribution of sixteen antibiotics belonging
      to four groups in surface water, sediment and groundwater samples from the
      Wangyang River (WYR), a typical river receiving sewage discharges were
      investigated. Laboratory analyses revealed that antibiotics were widely
      distributed in the studied area. The aqueous samples were unavoidably
      contaminated with antibiotics, and the target antibiotics present in high levels
      were oxytetracycline, tetracycline, chlortetracycline, ofloxacin,
      sulfamethoxazole, and trimethoprim, with maximum concentrations of the individual
      contaminant at 3.6*10(5), 9.7*10(3), 6.9*10(4), 1.2*10(4), 4.8*10(3), and
      1.1*10(3) ng L(-1), respectively. Oxytetracycline, tetracycline, ciprofloxacin
      and roxithromycin were the most frequently detected compounds in sediment
      samples, with maximum concentrations of the individual contaminant at 1.6*10(5),
      1.7*10(4), 2.1*10(3) and 2.5*10(3) ng g(-1), respectively. The results also
      revealed that the high intensity of aquaculture activities could contribute to
      the increasing levels of antibiotics in the area. According to the ratios of
      measured environmental concentration (MEC) to predicted no-effect concentration
      (PNEC), chlortetracycline, tetracycline, ofloxacin, ciprofloxacin, erythromycin
      H2O and sulfamethoxazole may present possible environmental risk to
      Pseudokirchneriella subcapitata, Synechococcus leopoliensis and M. aeruginosa.
      Attention should be given to the long-term ecological effects caused by the
      continuous discharge of antibiotics in the WYR area.

PMID- 25048916
TI  - Assessing developmental toxicity and estrogenic activity of halogenated bisphenol
      A on zebrafish (Danio rerio).
AB  - Halogenated bisphenol A (H-BPAs), widely used in industrial production, have been
      identified in various environmental matrices and detected in human serum and
      breast milk. The persistence and prevalence of H-BPAs in the environment
      underscore the need to in-depth understand their adverse effects to humans and
      other organisms. In the present study, zebrafish embryos/larvae were used as
      models to investigate the developmental toxicities of three H-BPAs, namely
      tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA), and bisphenol AF
      (BPAF). The half lethal concentration (LC50) values indicated that the rank order
      of toxicities of the chemicals were TCBPA>TBBPA>BPAF. Three H-BPAs exposure
      resulted in a variety of developmental lesions in the embryos/larvae, such as a
      delay in time to hatch, edema, and hemorrhage. The estrogenic activities of H
      BPAs were determined by means of in vivo vitellogenin (vtg) assay and in vitro
      MVLN assay. Here only BPAF specifically shows a stronger estrogenic activity than
      BPA both in in vivo and in vitro. These data suggest that TCBPA, TBBPA, and BPAF
      are more potent toxicants than BPA, and indicate that further research of the
      mechanisms on their toxicities is required. 

PMID- 25048917
TI  - Comparing three approaches in extending biotic ligand models to predict the
      toxicity of binary metal mixtures (Cu-Ni, Cu-Zn and Cu-Ag) to lettuce (Lactuca
      sativa L.).
AB  - Metals are always found in the environment as mixtures rather than as solitary
      elements. However, effect models such as biotic ligand models (BLMs) are usually
      derived for toxicity prediction of single metals. Our study aimed at predicting
      mixture toxicity of Cu-Ni, Cu-Zn and Cu-Ag combinations to lettuce (Lactucasativa
      L.) by combining BLMs with three toxicity indexes: the toxic unit, the overall
      amounts of metal ions bound to the biotic ligands and the toxic equivalency
      factor. The accumulation of metal ions at the biotic ligands was used to
      determine the toxic potency of metals alone or in combination. On the basis of
      parameters derived from toxicity assessment of individual metals, these three
      extended BLMs appeared to be all acceptable (p<0.0001) in assessing toxicity of
      diverse metal mixtures. The BLM-based approaches integrated competition between
      metal ions in assessing mixture toxicity and showed different predictive ability
      for each metal combination. The outcome of modeling suggested that the combined
      toxicity depends on the specific components of the metal mixtures. The best
      developed models assist in identifying the type of underlying toxic mechanisms of
      diverse metal mixtures in terrestrial plants. 

PMID- 25048918
TI  - Cancer risk of polycyclic aromatic hydrocarbons (PAHs) in the soils from Jiaozhou
      Bay wetland.
AB  - To estimate the cancer risk exposed to the PAHs in Jiaozhou Bay wetland soils, a
      probabilistic health risk assessment was conducted based on Monte Carlo
      simulations. A sensitivity analysis was performed to determine the input
      variables that contribute most to the cancer risk assessment. Three age groups
      were selected to estimate the cancer risk via four exposure pathways (soil
      ingestion, food ingestion, dermal contact and inhalation). The results revealed
      that the 95th percentiles cancer risks for children, teens and adults were
      9.11*10(-6), 1.04*10(-5) and 7.08*10(-5), respectively. The cancer risks for
      three age groups were at acceptable range (10(-6)-10(-4)), indicating no
      potential cancer risk. For different exposure pathways, food ingestion was the
      major exposure pathway. For 7 carcinogenic PAHs, the cancer risk caused by BaP
      was the highest. Sensitivity analysis demonstrated that the parameters of
      exposure duration (ED) and sum of converted 7 carcinogenic PAHs concentrations in
      soil based on BaPeq (CSsoil) contribute most to the total uncertainty. This study
      provides a comprehensive risk assessment on carcinogenic PAHs in Jiaozhou Bay
      wetland soils, and might be useful in providing potential strategies of cancer
      risk prevention and controlling. 

PMID- 25048919
TI  - Effect of sulfur dioxide on inflammatory and immune regulation in asthmatic rats.
AB  - BACKGROUND: Exposure to sulfur dioxide (SO2) increases asthma risk. Inflammatory
      and immune responses are typical in asthma disease. The exact effect of SO2 on
      modulation of the inflammatory and immune responses in asthmatic rats remains
      unclear. OBJECTIVES: Here we sought to investigate the molecular mechanisms
      underlying the NF-kappaB inflammatory pathway and the Th1/Th2 imbalance in
      asthmatic rats exposed to SO2. METHODS: Male Wistar rats were challenged by
      ovalbumin (OVA) or SO2 alone or together, and then mRNA and protein levels of
      some inflammatory and immune genes were measured. NF-kappaB nuclear translocation
      was analyzed. Bronchoalveolar lavage (BAL), inflammatory cell counts and
      histopathologic examination were performed. RESULTS: (1) OVA plus SO2 induced
      abnormal pathological changes and inflammatory responses in lung relative to
      exposure to OVA alone; (2) showing NF-kappaB nuclear translocation and activation
      through up-regulating IKKbeta mRNA and protein expression and down-regulating
      IkappaBalpha expression in the presence of OVA or OVA plus SO2; (3) OVA plus SO2
      significantly raised TNF-alpha and IL-6 levels in BALF compared with the OVA
      group; (4) SO2 markedly elevated IL-4 levels and decreased IFN-gamma levels in
      BALF in the asthmatic rats, stimulating IgE generation which was closely related
      to inhibiting the expression of Foxp3, a specific marker of regulatory T cells.
      CONCLUSIONS: SO2 affects the airway inflammatory and immune responses of the
      asthmatic rats and enhances the susceptibility to OVA by aggravating inflammatory
      responses in lungs, up-regulating pro-inflammatory cytokine expression, and
      causing the Th1/Th2 imbalance, which might contribute to the increased risk of
      asthma disease.

PMID- 25048920
TI  - Phytoremediation of anatoxin-a by aquatic macrophyte Lemna trisulca L.
AB  - The neurotoxin anatoxin-a (ANTX-a), one of the most common cyanotoxin, poses a
      health risk to people and can be lethal to aquatic organisms. This paper presents
      results on its bioremediation by the aquatic macrophyte Lemna trisulca. We show
      that the plant is resistant to the harmful impact of toxin and is capable of
      removing ANTX-a from water. Some of the ANTX-a concentrations which were used in
      our experiments were much higher than those found in natural conditions. The
      exposition of L. trisulca to 2.5 MUg ANTX-a/mL did not affect its biomass
      accumulation within 24 d. Significant decreases in biomass content by 21% and 30%
      were demonstrated in samples cultivated in media containing 12.5 MUg ANTX-a/mL
      after 18 and 24 day of experiment, respectively. One gram of fresh weight (f.w.)
      of L. trisulca cultured for 14 d in the media containing 50 MUg ANTX-a removed
      95% of the initial toxin concentration; for media with 250 MUg ANTX-a, 86% was
      removed. In tests of ANTX-a binding stability and degradation we transferred the
      macrophyte to fresh media without added toxin; within 14 d the content of
      accumulated ANTX-a in the macrophyte decreased by 76% (from initial 19.3 MUg ANTX
      a/gf.w.), 71% (from 37.3 MUg ANTX-a/g f.w.) and 47% (from 63.7 MUg ANTX-a/g
      f.w.). The quantity of ANTX-a released to media was minimal: from 3.5% to 5.1% of
      the initial bioaccumulated value. The data show that part of the ANTX-a was
      degraded. Mass spectra analyses did not indicate transformation of ANTX-a to
      already known forms. These findings suggest that L. trisulca has much potential
      as a phytoremediation agent for stabilization of aquatic environments.

PMID- 25048921
TI  - Total and inorganic arsenic levels in some marine organisms from Izmir Bay
      (Eastern Aegean Sea): a risk assessment.
AB  - The arsenic compounds in marine biota were evaluated from Izmir Bay (Eastern
      Aegean) and found that inorganic arsenic occurred as a minor fraction. No
      information is available on the annual variations of arsenic in important edible
      biota species from Izmir Bay. Fish and mussel samples were taken from different
      regions of Izmir Bay between 2009 and 2011 (n=854 individual specimens). The
      average percentages of inorganic arsenic to total arsenic for all biota samples
      were 3.43+/-3.38% with a range of 0.11-11.8%. The importance of speciation
      analysis for arsenic is supported by our work, because arsenic is ubiquitous in
      the ecosystem, and flexible toxicity of arsenic is based on chemical form. The
      average total As levels in Mullus barbatus were 6 times higher than Diplodus
      annularis and Mytilus galloprovincialis. This study also revealed that spatial
      variation influenced the arsenic levels in the fish samples and the highest
      concentrations of arsenic were found in Gediz site. Our study showed that
      estimated daily intakes of arsenic via consumption of flesh fish and shell fish
      were below the BMDL0.5 values established by FAO/WHO.

PMID- 25048922
TI  - Comparative study of toxicity of azo dye Procion Red MX-5B following biosorption
      and biodegradation treatments with the fungi Aspergillus niger and Aspergillus
      terreus.
AB  - Azo dyes are an important class of environmental contaminants and are
      characterized by the presence of one or more azo bonds (-N=N-) in their molecular
      structure. Effluents containing these compounds resist many types of treatments
      due to their molecular complexity. Therefore, alternative treatments, such as
      biosorption and biodegradation, have been widely studied to solve the problems
      caused by these substances, such as their harmful effects on the environment and
      organisms. The aim of the present study was to evaluate biosorption and
      biodegradation of the azo dye Procion Red MX-5B in solutions with the filamentous
      fungi Aspergillus niger and Aspergillus terreus. Decolorization tests were
      performed, followed by acute toxicity tests using Lactuca sativa seeds and
      Artemia salina larvae. Thirty percent dye removal of the solutions was achieved
      after 3 h of biosorption. UV-Vis spectroscopy revealed that removal of the dye
      molecules occurred without major molecular changes. The acute toxicity tests
      confirmed lack of molecular degradation following biosorption with A. niger, as
      toxicity to L. sativa seed reduced from 5% to 0%. For A. salina larvae, the
      solutions were nontoxic before and after treatment. In the biodegradation study
      with the fungus A. terreus, UV-Vis and FTIR spectroscopy revealed molecular
      degradation and the formation of secondary metabolites, such as primary and
      secondary amines. The biodegradation of the dye molecules was evaluated after 24,
      240 and 336 h of treatment. The fungal biomass demonstrated considerable affinity
      for Procion Red MX-5B, achieving approximately 100% decolorization of the
      solutions by the end of treatment. However, the solutions resulting from this
      treatment exhibited a significant increase in toxicity, inhibiting the growth of
      L. sativa seeds by 43% and leading to a 100% mortality rate among the A. salina
      larvae. Based on the present findings, biodegradation was effective in the
      decolorization of the samples, but generated toxic metabolites, while biosorption
      was effective in both decolorization and reducing the toxicity of the solutions.

PMID- 25048923
TI  - Influence of heavy metal rich tannery sludge on soil enzymes vis-a-vis growth of
      Tagetes minuta, an essential oil bearing crop.
AB  - Tannery sludge is available in plenty and is hazardous to environment as well as
      plant and animal life. It is very important to manage the tannery sludge in an
      environmentally sound manner. The aim of this study was to assess the physico
      chemical, microbial and biochemical properties of soil treated with different
      levels of sludge. In this study, Tagetes minuta an essential oil bearing crop was
      grown in two different textured soils treated with different levels of tannery
      sludge. Application of tannery sludge (TS) increased the growth and oil yield of
      plant and also the activity of urease and soil microbial biomass nitrogen (SMBN)
      when applied in 50:50 combinations of soil:sludge. The crop performed well in
      coarse soil with a soil:sludge ratio of 50:50. High concentration of tannery
      sludge exhibited inhibitory effect on SMBN and urease activity. Acid/alkaline
      phosphatase, dehydrogenase and soil microbial biomass carbon (SMBC) increased as
      the sludge concentration increased in soil. This may be due to high organic
      matter present in tannery sludge. Roots accumulated more metal than the shoot. No
      detectable amount of metal was found in oil of T.minuta. To test the relation
      between 20 characters principal component analysis (PCA) was performed. PCA
      analysis indicates that cation exchange capacity (CEC), SMBC, dehydrogenase, acid
      and alkaline phosphatases were grouped in group 1. SMBN, urease and cis-ocimene
      content in oil were in group 2 whereas biomasss, chlorophyll a, limonene, Z and E
      tagetone were in group 3. PC-I contributes 54% of total variance and PC-II
      contributes 38% of the total variance. The results concluded that T.minuta can
      mitigate metal toxicity by root absorption. Microbial activity and biomass of
      plant was higher in coarse soil with TS than fine soil with TS. 

PMID- 25048924
TI  - Sodium arsenite induced changes in survival, growth, metamorphosis and
      genotoxicity in the Indian cricket frog (Rana limnocharis).
AB  - Arsenic contamination of the environment is a matter of great concern.
      Understanding the effects of arsenic on aquatic life will act as biological early
      warning system to assess how arsenic could shape the biodiversity in the affected
      areas. Rapid decline in amphibian population in recent decades is a cause of
      major concern. Over the years, amphibians have been recognized as excellent bio
      indicators of environmental related stress. In the present study, we examined the
      toxic and genotoxic effects of sodium arsenite in the tadpoles of the Indian
      cricket frog (Rana limnocharis). Sodium arsenite at different concentrations (0,
      50, 100, 200 and 400 MUg L(-1)) neither induced lethality nor significantly
      altered body weight at metamorphosis. However, it accelerated the rate of
      metamorphosis at higher concentrations, reduced body size (snout-vent length) and
      induced developmental deformities such as loss of limbs. Besides, at
      concentration ranges between 100 and 400 MUg L(-1), sodium arsenite induced
      statistically significant genotoxicity at 24, 48, 72 and 96 h of the exposure in
      a concentration-dependent manner. However, it did not show time effects as the
      highest frequency was found between 48 and 72 h which remained steady
      subsequently. The genotoxicity was confirmed by comet assay in the whole blood
      cells. These findings suggest that arsenic at environmentally relevant
      concentrations has significant sub-lethal effects on R.limnocharis, which may
      have long-term fitness consequence to the species and may have similar
      implications in other aquatic life too.

PMID- 25048925
TI  - Ecological interactions affecting population-level responses to chemical stress
      in Mesocyclops leuckarti.
AB  - Higher tiers of ecological risk assessment (ERA) consider population and
      community-level endpoints. At the population level, the phenomenon of density
      dependence is one of the most important ecological processes that influence
      population dynamics. In this study, we investigated how different mechanisms of
      density dependence would influence population-level ERA of the cyclopoid copepod
      Mesocyclops leuckarti under toxicant exposure. We used a combined approach of
      laboratory experiments and individual-based modelling. An individual-based model
      was developed for M. leuckarti to simulate population dynamics under triphenyltin
      exposure based on individual-level ecological and toxicological data from
      laboratory experiments. The study primarily aimed to-(1) determine which life
      cycle processes, based on feeding strategies, are most significant in determining
      density dependence (2) explore how these mechanisms of density dependence affect
      extrapolation from individual-level effects to the population level under
      toxicant exposure. Model simulations showed that cannibalism of nauplii that were
      already stressed by TPT exposure contributed to synergistic effects of biotic and
      abiotic factors and led to a twofold stress being exerted on the nauplii, thereby
      resulting in a higher population vulnerability compared to the scenario without
      cannibalism. Our results suggest that in population-level risk assessment, it is
      easy to underestimate toxicity unless underlying ecological interactions
      including mechanisms of population-level density regulation are considered. This
      study is an example of how a combined approach of experiments and mechanistic
      modelling can lead to a thorough understanding of ecological processes in
      ecotoxicology and enable a more realistic ERA. 

PMID- 25048926
TI  - Vitellogenin of the northern leopard frog (Rana pipiens): development of an ELISA
      assay and evaluation of induction after immersion in xenobiotic estrogens.
AB  - An immunoassay for leopard frog (Rana pipiens) vitellogenin was developed for
      studying endocrine disruption. Male frogs were injected with estradiol-17beta to
      stimulate vitellogenin for purification. SDS-PAGE revealed high amounts of a 170
      180 kDa protein, which was confirmed to be vitellogenin by Western blotting.
      Vitellogenin was purified by DEAE chromatography and used to generate a
      polyclonal antibody. A competitive ELISA was developed for leopard frog
      vitellogenin with a detection limit of 6.0 ng mL(-1) and a working range of 20
      1000 ng mL(-1). The intra-assay coefficient of variation averaged 5.47% for
      control sera and 9.71% for estrogen-treated sera. The inter-assay coefficient of
      variation averaged 8.21% for control sera and 9.93% for estrogen-treated sera.
      Recovery of purified vitellogenin averaged 95.2%. Vitellogenin was measured in
      male frogs immersed in the estrogenic compound diethylstilbestrol (DES) for
      various times and doses. Serum vitellogenin was detected within five days after
      immersion in 1.0 mg L(-1) DES and levels continued to increase through 20 d. In a
      20-day dose-response experiment, serum vitellogenin was detected in frogs
      immersed in 0.01 mg L(-1) DES and vitellogenin concentration increased with dose.
      Immersion of frogs in one of several xenobiotic estrogens (nonylphenol,
      octylphenol, bisphenol-A) for 20 d did not increase vitellogenin for any
      treatment, suggesting that this frog may be less sensitive than fish to endocrine
      disruptors. Vitellogenin induction in R.pipiens may be a useful amphibian model
      system for field studies of endocrine disruption, due to its broad geographic
      range.

PMID- 25048927
TI  - Combined effects of lanthanum (III) chloride and acid rain on photosynthetic
      parameters in rice.
AB  - Rare earth elements (REEs) pollution and acid rain are environmental issues, and
      their deleterious effects on plants attract worldwide attention. These two issues
      exist simultaneously in many regions, especially in some rice-growing areas.
      However, little is known about the combined effects of REEs and acid rain on
      plants. Here, the combined effects of lanthanum chloride (LaCl3), one type of REE
      salt, and acid rain on photosynthesis in rice were investigated. We showed that
      the combined treatment of 81.6 MUM LaCl3 and acid rain at pH 4.5 increased net
      photosynthetic rate (Pn), stomatic conductance (Gs), intercellular CO2
      concentration (Ci), Hill reaction activity (HRA), apparent quantum yield (AQY)
      and carboxylation efficiency (CE) in rice. The combined treatment of 81.6 MUM
      LaCl3 and acid rain at pH 3.5 began to behave toxic effects on photosynthesis
      (decreasing Pn, Gs, HRA, AQY and CE, and increasing Ci), and the maximally toxic
      effects were observed in the combined treatment of 2449.0 MUM LaCl3 and acid rain
      at pH 2.5. Moreover, the combined effects of LaCl3 and acid rain on
      photosynthesis in rice depended on the growth stage of rice, with the maximal
      effects occurring at the booting stage. Furthermore, the combined treatment of
      high-concentration LaCl3 and low-pH acid rain had more serious effects on
      photosynthesis in rice than LaCl3 or acid rain treatment alone. Finally, the
      combined effect of LaCl3 and acid rain on Pn in rice resulted from the changes in
      stomatic (Gs, Ci) and non-stomatic (HRA, AQY and CE) factors.

PMID- 25048928
TI  - Estrogenic and androgenic activities of TBBA and TBMEPH, metabolites of novel
      brominated flame retardants, and selected bisphenols, using the XenoScreen XL
      YES/YAS assay.
AB  - The present study investigated and compared the estrogenic and androgenic
      activities of the three different classes of environmental pollutants and their
      metabolites using the XenoScreen XL YES/YAS assay, which has advantages compared
      with the original YES/YAS protocol. Contrary to the parent brominated flame
      retardants TBB and TBPH, which demonstrated no or very weak (anti)estrogenic or
      (anti)androgenic activities, their metabolites, TBBA and TBMEPH, exhibited anti
      estrogenic (IC50 for TBBA=31.75 MUM and IC50 for TBMEPH=0.265 MUM) and anti
      androgenic (IC50 for TBBA=73.95 MUM and IC50 for TBMEPH=2.92 MUM) activities.
      These results reveal that metabolism can enhance the anti-estrogenic and anti
      androgenic effects of these two novel brominated flame retardants. Based on the
      activities of BPAF, BPF, BPA and MBP, we can conclude that the XenoScreen XL
      YES/YAS assay gives comparable results to the (anti)estrogenic or
      (anti)androgenic assays that are reported in the literature. For BPA, it was
      confirmed previously that the metabolite formed after an ipso-reaction
      (hydroxycumyl alcohol) exhibited higher estrogenic activity compared with the
      parent BPA, but this was not confirmed for BPAF and BPF ipso-metabolites, which
      were not active in the XenoScreen YES/YAS assay. Among the substituted BPA
      analogues, bis-GMA exhibited weak anti-estrogenic activity, BADGE demonstrated
      weak anti-estrogenic and anti-androgenic activities (IC50=13.73 MUM), and the
      hydrolysed product BADGE.2H2O demonstrated no (anti)estrogenic or
      (anti)androgenic activities.

PMID- 25048929
TI  - Heavy metal concentrations in Black-tailed Gull (Larus crassirostris) chicks,
      Korea.
AB  - The objectives of this study were to quantify concentrations of heavy metals in
      livers and stomach contents of Black-tailed Gull (Larus crassirostris) chicks
      from two islands in Korea. Iron and manganese concentrations were significantly
      higher in chick livers at Hongdo Island compared to Rando Islnad. In contrast,
      zinc, copper and cadmium concentrations were significantly higher at Rando Island
      than Hongdo Island. On Hongdo Island, Black-tailed Gull chicks at a lighthouse
      site had higher lead concentrations in livers and stomach contents than at a
      nearby reference site and stomach contents of Black-tailed Gull chicks had
      significantly higher lead concentrations than regurgitated diets. In Hongdo
      Island, manganese, lead and cadmium concentrations were significantly correlated
      between livers and stomach contents. Essential elements such as iron, zinc,
      manganese and copper concentrations from the present study were within the range
      reported for other seabird species including gulls. Livers of four individual
      gull chicks (13.3%) were at a level considered lead exposed (6-30 MUg g(-1) dry
      weight), but cadmium concentrations in all specimens were within the background
      level (<3 MUg g(-1) dry weight) for wild birds. Elevated lead concentrations on
      lighthouse site may be attributed to ingestion of paint chips and these
      concentrations may negatively affect chick behavior, growth and survival.

PMID- 25048930
TI  - Bimodal responses of cells to trace elements: insights into their mechanism of
      action using a biospectroscopy approach.
AB  - Understanding how organisms respond to trace elements is important because some
      are essential for normal bodily homeostasis, but can additionally be toxic at
      high concentrations. The inflection point for many of these elements is unknown
      and requires sensitive techniques capable of detecting subtle cellular changes as
      well as cytotoxic alterations. In this study, we treated human cells with arsenic
      (As), copper or selenium (Se) in a dose-response manner and used attenuated total
      reflection Fourier-transform infrared (ATR-FTIR) microspectroscopy combined with
      computational analysis to examine cellular alterations. Cell cultures were
      treated with As(V), Cu(2+) or Se(IV) at concentrations ranging from 0.001 mg L(
      1) to 1000 mg L(-1) and their effects were spectrochemically determined. Results
      show that As(V) and Cu(2+) induce bimodal dose-response effects on cells; this is
      in line with hormesis-driven responses. Lipids and proteins seem to be the main
      cell targets for all the elements tested; however, each compound produced a
      unique fingerprint of effect. Spectral biomarkers indicate that all test agents
      generate reactive oxygen species (ROS), which could either stimulate repair
      mechanisms or induce damage in cells.

PMID- 25048931
TI  - Cadmium resistance in extremely halophilic archaeon Haloferax strain BBK2.
AB  - Halophilic archaea are prevalent in highly saline habitats. Haloferax strain BBK2
      is an orange pigmented, exopolysaccharide (EPS) producing extremely halophilic
      archaeon, isolated from solar salterns of Ribandar, Goa, India. It grew in
      varying pH (5-10) and NaCl concentration (10-30%). The isolate grew well in
      complex (NTYE) and minimal media (NGSM) in presence of heavy metal cadmium (Cd)
      up to 4.0 mM (805.28 mg L(-1)) concentration. The optimum growth in the presence
      and absence of Cd was seen at a pH range of 7-9 and salinity of 15-25%. The
      growth kinetics of the isolate in NTYE showed a specific growth rate (MUmax) of
      0.352 with generation time of 1.968 days. In presence of 1mM Cd, the MUmax was
      0.325 day(-1) and generation time was 2.132 days. In NGSM, the MUmax decreased
      from 0.517 day(-1) (in control) to 0.265 day(-1) in 1mM Cd while, the doubling
      time increased from 1.34 days in control to 2.615 days in presence of 1 mM Cd.
      SDS PAGE of the whole cell protein extracts showed overexpressed proteins of
      74.14 and 40 kDa. The scanning electron microscopy, energy dispersive X-ray
      spectroscopy (SEM-EDX) analysis of the intact cells and cells disrupted by
      dialysis revealed that Cd was bound onto the cells, which was further confirmed
      by AAS, FTIR and XRD analysis.

PMID- 25048932
TI  - Combined toxicity of butachlor, atrazine and lambda-cyhalothrin on the earthworm
      Eisenia fetida by combination index (CI)-isobologram method.
AB  - Pesticides in the environment do not appear singly and usually occur as complex
      mixtures and their combined effect may exhibit toxicity to organisms. The
      individual and combined toxicities of two herbicides, atrazine and butachlor and
      an insecticide lambda-cyhalothrin have been examined to the earthworm Eisenia
      fetida, as a non-target terrestrial organism, in artificial soil and filter paper
      tests. The order of toxicity for the individual pesticides was ranked as
      atrazine>lambda-cyhalothrin>butachlor in both tests. We applied the combination
      index (CI)-isobologram method which is widely used to study chemical interactions
      to determine the nature of toxicological interactions of the pesticides and it
      allows computerized quantitation of synergism, additive effect and antagonism.
      For most cases in artificial soil test, synergism was observed in majority of the
      mixtures except for the combination of butachlor plus lambda-cyhalothrin. This
      particular combination displayed opposite interaction in filter paper test. The
      CI method was compared with the classical models of Concentration Addition (CA)
      and Independent Action (IA) and we found that CI method could accurately predict
      the combined toxicity and can serve as a useful tool in ecotoxicological risk
      assessment. 

PMID- 25048933
TI  - Contrasting ecotoxicity effects of zinc on growth and photosynthesis in a
      neutrophilic alga (Chlamydomonas reinhardtii) and an extremophilic alga
      (Cyanidium caldarium).
AB  - This study aimed to determine the contrasting ecotoxicity effects of zinc on
      growth and photosynthesis in a neutrophilic (Chlamydomonas reinhardtii) and an
      extremophilic (Cyanidium caldarium) alga. Experiments were carried out to see if
      cells acclimated to zinc would respond differently to cells that were unexposed
      to zinc. The study also aimed to see if extremophiles displayed different
      acclimation properties to neutrophiles. Results showed that the neutrophilic alga
      C. reinhardtii, was more susceptible to free zinc and had a lower IC50 value than
      the extremophile, however its stress response protected the photosynthetic
      apparatus. Upon acclimation, the photosynthetic abilities of C. reinhardtii were
      not significantly compromised when exposed to toxic levels of free zinc. On the
      other hand, C. caldarium had a stress response which allowed it to tolerate
      significantly higher amounts of free zinc in its environment compared to C.
      reinhardtii , however the stress response did not protect the photosynthetic
      apparatus, and upon acclimation C. caldarium was no better equipped to protect
      its photosynthetic integrity than unexposed cells. 

PMID- 25048934
TI  - Assessments of chromium (and other metals) in vegetables and potential bio
      accumulations in humans living in areas affected by tannery wastes.
AB  - Chromium (Cr) commonly enters the food chain through uptake by vegetables.
      However, accurate prediction of plant uptake of Cr (and other metals) still
      remains a challenge. In this study, we evaluated 5 indices of availability for Cr
      (and other metals) to identify reliable predictors of metal transfer from soils
      to garlic, onion, bokchoy, radish and celery grown in soils impacted by tannery
      wastes. The potential bio-accumulation of Cr in humans was calculated from the Cr
      content of vegetable predicted by the best bio-availability index, amounts of
      vegetable consumed and recommended daily doses for Cr. Our results show that soil
      total Cr is the best predictor of Cr transfer from soils to onion (Cr in
      onion=8.51+0.005 Total Cr) while Cr extractable by Synthetic Precipitation
      Leaching Procedure at pH 5 correlates very well with Cr uptake by bokchoy (Cr
      bokchoy=5.86+7.32 SPLP-5 Cr) and garlic (Cr garlic=7.63+2.36 SPLP-5 Cr). The
      uptake of Cr by radish and celery could not be reliably estimated by any of the 5
      indices of availability tested in this study. Potential bio-accumulation of Cr in
      humans (BA-Cr) increases from soils with low Cr (BA-Cr=11.5) to soil with high
      total Cr (BA-Cr=31.3). Due to numerous soil factors affecting the behavior of Cr
      in soils and the physiological differences among vegetables, we suggest that the
      prediction of the transfer of Cr (and other metals) from soils to plants should
      be specific to site, metal and vegetable. Potential bio-accumulation of Cr in
      humans can be derived from a transfer function of Cr from soils to plants and the
      human consumption of vegetables. 

PMID- 25048935
TI  - Benefits from hazards: mixture hormesis induced by [emim]Cl despite its
      individual inhibitions.
AB  - The threshold model based on monotonic concentration-response curves (CRCs) is
      unsuitable to assess the risk of chemicals with non-monotonic CRCs. The non
      monotonic CRCs of mixtures may relate to the characteristics of some individual
      component. To reveal the cause of the mixtures resulting in the non-monotonic
      CRCs, we used the microplate toxicity analysis to determine the toxicity effects
      of six 1-alkyl-3-methyl-imidazolium ([amim]X) salts and their mixtures on Vibrio
      qinghaiensis sp.-Q67 (Q67). It was shown that the CRCs of six [amim]X salts are
      monotonic S-shaped while those of the senary mixtures designed by the uniform
      design ray (UD-ray) are all non-monotonic. The mixtures were further split into
      two ternary mixtures, one containing 1-ethyl-3-methyl-imidazolium ([emim]X) salts
      (noted as UTE) and the other one containing 1-butyl-3-methyl-imidazolium
      ([bmim]X) salts (noted as UTB). It was found that the CRCs of UTE mixtures are
      all non-monotonically J-shaped, while only one (UTB-R3) among UTB mixtures has a
      little stimulating effect and the CRCs of the other three mixtures (UTB-R1, UTB
      R2 and UTB-R4) are monotonic. The CRCs of the binary mixtures designed by the
      direct equipartition ray design (EquRay) procedure were further examined. The
      CRCs of the mixtures containing [emim]Cl are non-monotonic J-shaped while those
      of the mixtures without [emim]Cl are still monotonic. Thus, it can conclude that
      it is [emim]Cl that causes the non-monotonic CRCs in [amim]X mixtures, even
      though the CRC of individual [emim]Cl is monotonic. 

PMID- 25048936
TI  - Organ-dependent response in antioxidants, myoglobin and neuroglobin in goldfish
      (Carassius auratus) exposed to MC-RR under varying oxygen level.
AB  - Cyanobacterial bloom, a common phenomenon nowadays often results in the depletion
      of dissolved oxygen (hypoxia) and releases microcystin-RR (MC-RR) in the water.
      Information on the combined effects of MC-RR and hypoxia on the goldfish is
      lacking, therefore, this study is aimed at evaluating the effect of two doses of
      MC-RR on the antioxidants and globin mRNA of goldfish under normoxia, hypoxia and
      reoxygenation. The result showed that MC-RR at both doses (50 and 200 MUg kg(-1)
      body weight) significantly (p<0.05) induced superoxide dismutase activities in
      the liver and kidney but catalase activities and total antioxidant capacity were
      low in these organs during hypoxia and reoxygenation compared to normoxia and
      control. Myoglobin and neuroglobin mRNAs in MC-RR group were significantly
      induced in the brain only and are believed to protect the brain from oxidative
      damage. However, other organs were unprotected and extensive damage was observed
      in the liver cells. Our results clearly demonstrated that MC-RR and hypoxia
      reoxygenation transitions were synergistically harmful to the goldfish and could
      impair its adaptation to hypoxia, especially during reoxygenation.

PMID- 25048937
TI  - Low-dose bisphenol A disrupts gonad development and steroidogenic genes
      expression in adult female rare minnow Gobiocypris rarus.
AB  - Bisphenol A (BPA), an estrogenic monomer, has attracted many researchers to study
      its adverse effects in animal reproduction, especially in fish. To explore the
      effects of low dose BPA on adult female rare minnow Gobiocypris rarus, we exposed
      the fish to BPA at nominal concentrations of 5, 15, and 50 MUg L(-1) for 14 and
      35 d. The 35-d BPA exposure at 50 MUg L(-1) had obviously suppressive effects on
      oocyte development, and BPA at all the three concentrations in both exposure
      durations of 14 and 35 d had stimulative effects on hepatic vitellogenin (vtg)
      transcription. BPA at lower concentrations (5 and 15 MUg L(-1)) exhibited
      stimulative effects on the expressions of ovarian steroidogenic genes while at
      higher concentration (50 MUg L(-1)) displayed inhibitive effects. Analysis of
      ovarian steroidogenic genes 5'-flanking regions and mRNA expressions of their
      potential regulatory factors revealed that the BPA-mediated actions on
      steroidogenesis in G. rarus ovary probably involve estrogen receptor (Esr) and
      androgen receptor (Ar) signaling, nuclear receptor subfamily 5, group A, number 1
      (Nr5a1) pathway, and epigenetic regulation.

PMID- 25048938
TI  - Antifungal activity and chemical composition of twenty essential oils against
      significant indoor and outdoor toxigenic and aeroallergenic fungi.
AB  - Health affecting, loss-inducing or otherwise harmful fungal pathogens (molds)
      pose a serious challenge in many areas of human activities. On the contrary,
      frequent use of synthetic fungicides is undesirable in some cases and may be
      equally problematic. Moreover, the ever more increasing fungal resistance against
      commercial synthetic fungicides justifies development of rising efforts to seek
      new effective, while environmentally friendly alternatives. Botanical fungicides
      based on Essential oils (EOs) undoubtedly provide such an alternative. The study
      explores the efficacy of 20 EOs against Alternaria alternata, Stachybotrys
      chartarum, Cladosporium cladosporioides and Aspergillus niger, related to
      abundance of majority active substances. Minimum inhibitory concentration (MIC100
      and MIC50) was evaluated. GC-MS analysis revealed high abundance of highly
      effective phenolic compounds whose different molecular structures correlates with
      differences in EOs efficacy. The efficacy of some EOs, observed in our study, can
      be similar to the levels of some synthetic fungicides used in medicine and
      agriculture e.g. sometimes problematic azole-based formulations. Thanks to the
      EOs environmental safety and natural origin, they offer the potential to become
      an alternative where the use of synthetic fungicides is impossible for various
      reasons. 

PMID- 25048939
TI  - Does fish reproduction and metabolic activity influence metal levels in fish
      intestinal parasites, acanthocephalans, during fish spawning and post-spawning
      period?
AB  - Application of fish intestinal parasites, acanthocephalans, as bioindicators in
      metal exposure assessment usually involves estimation of their metal levels and
      bioconcentration factors. Metal levels in parasite final host, fishes, are
      influenced by fish physiology but there is no data for acanthocephalan metal
      levels. Gastrointestinal Zn, Fe, Mn, Cd, Ag levels in European chub (Squalius
      cephalus L.) from the Sava River were significantly higher during chub spawning
      (April/May) compared to the post-spawning period (September). In acanthocephalans
      (Pomphorhynchus laevis and Acanthocephalus anguillae) significantly higher metal
      levels during chub spawning were observed only for Zn in P. laevis.
      Bioconcentration factors were twice as high for Fe, Mn, Ag, Pb in the post
      spawning period, probably as a consequence of lower gastrointestinal metal levels
      in fish rather than metal exposure. Therefore, bioconcentration factors should be
      interpreted with caution, due to their possible variability in relation to fish
      physiology. In addition, gastrointestinal Cu, Cd and Pb levels were lower in
      infected than uninfected chub, indicating that metal variability in fishes might
      be affected by the presence of acanthocephalans. 

PMID- 25048940
TI  - Tissue distribution, characterization and in vitro inhibition of B-esterases in
      the earwig Forficula auricularia.
AB  - Earwigs are important natural enemies of numerous pests in pome fruit orchards
      worldwide. Studying the effects of agricultural practices on these biological
      control agents is important for understanding its vulnerability in the field. The
      aim of this study was to characterize the B-esterase activities in the European
      earwig Forficula auricularia and to evaluate in vitro its sensitivity to
      organophosphate and carbamate pesticides. Acetylcholinesterase (AChE) activity
      was mainly measured with 1.5 mM acetylthiocholine as the substrate in the
      microsomal fraction of earwig heads (70% of total AChE activity).
      Carboxylesterase (CbE) activities were measured with three substrates [5 mM 4
      nitrophenyl acetate (4-NPA), 1mM 4-nitrophenyl valerate (4-NPV), and 2 mM alpha
      naphtyl acetate (alpha-NA)] to examine different isoenzymes, which were present
      mainly in the cytosolic fraction (about 70-88% of total activities) of all earwig
      tissues. CbE activity was higher than AChE activity, especially with alpha-NA,
      then 4-NPA and lastly 4-NPV. Chlorpyrifos-oxon an organophosphate, and carbaryl a
      carbamate pesticide, inhibited AChE and CbE activities in a concentration
      dependent manner. Earwig CbE activities showed a stronger sensitivity to
      organophosphate than AChE, with the strongest effect for chlorpyrifos-oxon on
      male carboxylesterase activities. CbE and AChE showed about the same sensitivity
      to carbamate pesticides regardless of sex. These results suggest that B-type
      esterases in the European earwig F.auricularia are suitable biomarkers of
      pesticide exposure.

PMID- 25048941
TI  - Acclimation and adaptation to common marine pollutants in the copepod Tigriopus
      californicus.
AB  - Establishing water quality criteria using bioassays is complicated by variation
      in chemical tolerance between populations. Two major contributors to this
      variation are acclimation and adaptation, which are both linked to exposure
      history, but differ in how long their effects are maintained. Our study examines
      how tolerance changes over multiple generations of exposure to two common marine
      pollutants, copper (Cu) and tributyltin oxide (TBTO), in a sexually reproducing
      marine copepod, Tigriopus californicus. Lines of T. californicus were chronically
      exposed to sub-lethal levels of Cu and TBTO for 12 generations followed by a
      recovery period of 3 generations in seawater control conditions. At each
      generation, the average number of offspring produced and survived to 28 d was
      determined and used as the metric of tolerance. Lines exposed to Cu and TBTO
      showed an overall increase in tolerance over time. Increased Cu tolerance arose
      by generation 3 in the chronically exposed lines and was lost after 3 generations
      in seawater control conditions. Increased TBTO tolerance was detected at
      generation 7 and was maintained even after 3 generations in seawater control
      conditions. It was concluded from this study that tolerance to Cu is consistent
      with acclimation, a quick gain and loss of tolerance. In contrast, TBTO tolerance
      is consistent with adaptation, in which onset of tolerance was delayed relative
      to an acclimation response and maintained in the absence of exposure. These
      findings illustrate that consideration of exposure history is necessary when
      using bioassays to measure chemical tolerance.

PMID- 25048942
TI  - Binding between lead ions and the high-abundance serum proteins.
AB  - The interaction between three of the most abundant bovine serum proteins (serum
      albumin, transferrin and IgG) with Pb(2+) was investigated using
      electrochemistry. The data was used to construct a new theoretical model of
      Pb(2+) binding to the high-abundance serum proteins under non-ideal conditions.
      The binding constants (beta) of Pb(2+) to the individual proteins and a mixture
      of proteins were measured according to a new theoretical equation (non-ideal
      state) as well as the McGhee-Von Hippel equation (ideal state). Differences
      between the models suggested that the beta values obtained using the non-ideal
      state model was more realistic. Protein-protein interactions and micro
      environmental influences affected binding between Pb(2+) and the high-abundance
      serum proteins. We included a micro-environmental influence factor for the model
      (Fm), which accurately quantified the effect of micro-environment of the proteome
      of Pb(2+) binding with the serum proteins. This research provides a useful
      reference of theoretical and experimental work regarding heavy-metal binding
      interactions with serum proteins. 

PMID- 25048943
TI  - Urinary levels of bisphenol analogues in residents living near a manufacturing
      plant in south China.
AB  - The use of bisphenol A (BPA) has been restricted in many countries because of its
      potential health effects. As a result of these restrictions, a group of bisphenol
      analogues that are structurally similar to BPA have been developed as the
      alternatives for industrial applications. However, latest researches indicated
      that these chemicals have similar endocrine-disrupting effects as BPA in humans.
      Moreover, only a limited number of studies have attempted to monitor the exposure
      level in humans of other bisphenol analogues. In the present study, the
      concentrations of seven bisphenols, including bisphenol S (BPS), bisphenol F
      (BPF), bisphenol B (BPB), BPA, bisphenol AF (BPAF), tetrachlorobisphenol A
      (TCBPA) and tetrabromobisphenol A (TBBPA), in human urine samples were measured
      by liquid chromatography coupled to mass spectrometry (LC-MS/MS) following the
      enzymatic hydrolysis of glucuronidase/arylsulfatase and liquid-liquid extraction
      (LLE). Under the optimised conditions, high recoveries (81.6-116.8%) were
      obtained for all the analytes, and the relative standard deviations (RSD, %) were
      less than 16.4% (n=6). The isotopic internal standard calibration curves for each
      of the target compounds exhibited excellent linearity (r(2)>0.99) and the limit
      of quantification (LOQ) for the analytes in urine ranged from 0.024 to 0.310 ng
      mL(-1). The method was applied to investigate the urinary levels of these seven
      bisphenols in a cohort of residents living near a BPAF manufacturing plant in
      south China. BPS, BPF, BPA and BPAF were detected in urine samples at
      concentrations ranging from <LOQ to a few ng mL(-1), whereas BPB, TCBPA and TBBPA
      were not detected. This is the first study to report the occurrence of BPF and
      BPAF in human urine samples. The availability of rapid and simple analytical
      methods may be highly useful for the future biomonitoring of these compounds.

PMID- 25048944
TI  - Elucidating differences in metal absorption efficiencies between terrestrial soft
      bodied and aquatic species.
AB  - It is unknown whether metal absorption efficiencies in terrestrial soft-bodied
      species can be predicted with the same metal properties as for aquatic species.
      Here, we developed models for metal absorption efficiency from the dissolved
      phase for terrestrial worms and several aquatic species, based on 23 metal
      physicochemical properties. For the worms, the absorption efficiency was
      successfully related to 7 properties, and is best predicted with the ionic
      potential. Different properties (8 in total) were found to be statistically
      significant in regressions predicting metal absorption in aquatic species, with
      the covalent index being the best predictor. It is hypothesized that metal
      absorption by soft-bodied species in soil systems is influenced by the rate of
      metal supply to the membrane, while in aquatic systems accumulation is solely
      determined by metal affinity to membrane bound transport proteins. Our results
      imply that developing predictive terrestrial bioaccumulation and toxicity models
      for metals must consider metal interactions with soil solids. This may include
      desorption of a cation bound to soil solids through ion exchange, or metal
      release from soil surfaces involving breaking of metal-oxygen bonds. 

PMID- 25048945
TI  - Effect of 17beta-estradiol on striatal dopaminergic transmission induced by
      permethrin in early childhood rats.
AB  - A positive effect of estrogen treatment has been observed in neurodegenerative
      diseases such as Parkinson's disease. Since 17beta-estradiol can modulate
      positively dopaminergic system, here we sought to evaluate the effect of 17beta
      estradiol supplementation on an animal model developing dopaminergic alterations
      on nucleus of striatum after neonatal exposure to permethrin pesticide. The goal
      of the study was to verify if the co-treatment with 17beta-estradiol could
      protect against the damage induced by pesticide exposure in early life.
      Permethrin treated rats showed a decrease of dopamine and Nurr1 gene expression
      in striatum, while a more pronounced decrease of dopamine was observed in rats co
      administered with permethrin+17beta-estradiol. No difference between control and
      permethrin treated rats was observed in both mRNA of ERalpha and ERbeta, whereas
      the rats co-administered with permethrin+17beta-estradiol showed a down
      regulation of ERalpha expression. The in vitro studies showed that permethrin, at
      high concentration may have an antagonist effect on ERalpha and even more
      pronounced in ERbeta, thus suggesting that permethrin may block the estrogen
      neuroprotective effects. In conclusion, in male rats, the administration of
      estrogen further enhanced the impairment of dopaminergic transmission due to
      exposure to permethrin. 

PMID- 25048946
TI  - Processing of abasic site damaged lesions by APE1 enzyme on DNA adsorbed over
      normal and organomodified clay.
AB  - The efficiency of the apurinic/apyrimidinic endonuclease (APE1) DNA repair enzyme
      in the processing of abasic site DNA damage lesions at precise location in DNA
      oligomer duplexes that are adsorbed on clay surfaces was evaluated. Three
      different forms of clay namely montmorillonite, quaternary ammonium salt modified
      montmorillonite and its boiled counterpart i.e. partially devoid of organic
      moiety were used for a comparative study of adsorption, desorption and DNA repair
      efficiency on their surfaces. The interaction between the DNA and the clay was
      analysed by X-ray diffraction, Atomic force microscopy, UV-Vis spectroscopy and
      Infrared spectroscopy. The abasic site cleavage efficiency of APE1 enzyme was
      quantitatively evaluated by polyacrylamide gel electrophoresis. Apart from the
      difference in the DNA adsorption or desorption capacity of the various forms of
      clay, substantial variation in the repair efficiency of abasic sites initiated by
      the APE1 enzyme on the clay surfaces was observed. The incision efficiency of
      APE1 enzyme at abasic sites was found to be greatly diminished, when the DNA was
      adsorbed over organomodified montmorillonite. The reduced repair activity
      indicates an important role of the pendant surfactant groups on the clay surfaces
      in directing APE1 mediated cleavage of abasic site DNA damage lesions. 

PMID- 25048947
TI  - Thyromimetic actions of tetrabromobisphenol A (TBBPA) in steatotic FaO rat
      hepatoma cells.
AB  - Tetrabromobisphenol A (2,2-bis(3,5-dibromo-4-hydroxyphenyl propane-TBBPA) is the
      most produced brominated flame retardant, detected in the environment and in
      biological samples. TBBPA shares structural similarities with thyroid hormones
      (THs), and it has been shown to interfere with different aspects of TH
      physiology, this raising concern on its possible effects as an endocrine
      disruptor in humans and wildlife. THs play a major role in lipid metabolism, with
      the liver representing one of their main target tissues. At the cellular level,
      THs act through interactions with TH receptors (TRs), as well as through TR
      independent mechanisms. Rat hepatoma FaO cells (a liver cell line defective for
      functional TRs) overloaded with lipids have been utilized as a model to
      investigate the anti-steatotic effects of THs in the hepatocyte. In this work,
      the possible effects of TBBPA in steatotic FaO cells were investigated. Exposure
      to TBBPA for 24 h reduced triglyceride (TAG) content and the size of lipid
      droplets (LDs); similar effects were obtained with equimolar doses (10(-6) M) of
      T3 (3,3',5-L-triiodothyronine). TBBPA and T3 showed common effects on
      transcription of genes involved in lipid homeostasis. In particular, TBBPA mainly
      up-regulated mRNA levels for LD-associated oxidative tissue-enriched PAT protein
      (OXPAT), peroxisome proliferator-activated receptor (PPAR) isoform beta/delta,
      and the mitochondrial uncoupling protein 2 (UCP2). The results demonstrate that
      TBBPA can decrease lipid accumulation in steatotic cells through stimulation of
      oxidative pathways. These data identify novel thyromimetic actions of TBBPA at
      the cellular level.

PMID- 25048948
TI  - An empirical assessment of the focal species hypothesis.
AB  - Biodiversity surrogates and indicators are commonly used in conservation
      management. The focal species approach (FSA) is one method for identifying
      biodiversity surrogates, and it is underpinned by the hypothesis that management
      aimed at a particular focal species will confer protection on co-occurring
      species. This concept has been the subject of much debate, in part because the
      validity of the FSA has not been subject to detailed empirical assessment of the
      extent to which a given focal species actually co-occurs with other species in an
      assemblage. To address this knowledge gap, we used large-scale, long-term data
      sets of temperate woodland birds to select focal species associated with
      threatening processes such as habitat isolation and loss of key vegetation
      attributes. We quantified co-occurrence patterns among focal species, species in
      the wider bird assemblage, and species of conservation concern. Some, but not
      all, focal species were associated with high levels of species richness. One of
      our selected focal species was negatively associated with the occurrence of other
      species (i.e., it was an antisurrogate)-a previously undescribed property of
      nominated focal species. Furthermore, combinations of focal species were not
      associated with substantially elevated levels of bird species richness, relative
      to levels associated with individual species. Our results suggest that although
      there is some merit to the underpinning concept of the FSA, there is also a need
      to ensure that actions are sufficiently flexible because management tightly
      focused on a given focal species may not benefit some other species, including
      species of conservation concern, such of which might not occur in species-rich
      assemblages.

PMID- 25048950
TI  - Research highlights: increasing paper possibilities.
AB  - In this issue we highlight three recent papers that demonstrate new strategies to
      extend the capabilities of paper microfluidics. Paper (a mesh of porous fibers)
      has a long history as a substrate to perform biomolecular assays. Traditional
      lateral flow immunoassays (LFAs) are widely used for rapid diagnostic tests, and
      perform well when a yes or no answer is required and the analyte of interest is
      at relatively high concentrations. High concentrations are required because
      usually only a small volume of analyte-containing fluid flows past the detection
      region, leading to a limited signal. Further, the small pores within paper
      matrices prevent the use of paper to control the flow of larger particles and
      cells, limiting the use of paper microfluidics for cell-based diagnostics. The
      work we highlight addresses these important unmet challenges in paper
      microfluidics: enriching low concentration analytes to a higher concentration in
      a smaller volume that can be processed effectively, and using paper to pump flows
      in larger channels amenable to cells. Applying these new approaches may allow
      diagnosis of disease states currently technically unachievable using current LFA
      systems, while maintaining many of the "un-instrumented" advantages of an assay
      on self-wicking paper. 

PMID- 25048949
TI  - The CD8 antiviral factor (CAF) can suppress HIV-1 transcription from the long
      terminal repeat (LTR) promoter in the absence of elements upstream of the CATATAA
      box.
AB  - BACKGROUND: The CD8 Antiviral Factor (CAF) suppresses viral transcription from
      the HIV-1 Long Terminal Repeat (LTR) promoter in a non-cytolytic manner. However,
      the region on the LTR upon which CAF acts is unknown. Our objective was to
      determine the region on the LTR upon which CAF acts to suppress HIV-1
      transcription. METHODS: Serial deletions of the LTR from the 5' end and
      inactivating point mutations were made. RESULTS: Serial deletions of the LTR from
      the 5' end indicated the importance of a short ~120 bp segment, containing the 3
      SpI sites, CATA box (used by HIV-1 instead of the TATA box) and TAR region, in
      the suppressive process. Introduction of deletions or inactivating point
      mutations in the SpI sites or deletion of the TAR region did not abolish CAF
      mediated transcriptional suppression. Yet, CAF-mediated transcriptional
      suppression was still retained in the HIV-1 CATA-TAR segment. CONCLUSION: CAF is
      able to suppress transcription from the LTR lacking all the elements upstream of
      the CATA box. Our results suggest that the HIV-1 CATA box may be responsible for
      CAF-mediated suppression of transcription from the HIV-1 LTR.

PMID- 25048951
TI  - CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker
      of non-alcoholic steatohepatitis.
AB  - BACKGROUND & AIMS: Perpetuate liver inflammation is crucial in the pathogenesis
      of non-alcoholic steatohepatitis (NASH). Expression of CXCL10, a pro-inflammatory
      cytokine, correlates positively with obesity and type 2 diabetes. Whether CXCL10
      plays a role in NASH was unknown. We aimed to investigate the functional and
      clinical impact of CXCL10 in NASH. METHODS: Cxcl10 gene-deleted (Cxcl10(-/-)) and
      C57BL/6 wild type (WT) mice were fed a methionine- and choline-deficient (MCD)
      diet for 4 or 8 weeks. In other experiments, we injected neutralizing anti-CXCL10
      mAb into MCD-fed WT mice. Human serum was obtained from 147 patients with biopsy
      proven non-alcoholic fatty liver disease and 73 control subjects. RESULTS: WT
      mice, fed the MCD diet, developed steatohepatitis with higher hepatic CXCL10
      expression. Cxcl10(-/-) mice were refractory to MCD-induced steatohepatitis. We
      further revealed that CXCL10 was associated with the induction of important pro
      inflammatory cytokines (TNF-alpha, IL-1beta, and MCP-1) and activation of the NF
      kappaB pathway. CXCL10 was linked to steatosis through upregulation of the
      lipogenic factors SREBP-1c and LXR, and also to oxidative stress (upregulation of
      CYP2E1 and C/EBPbeta). Blockade of CXCL10 protected against hepatocyte injury in
      vitro and against steatohepatitis development in mice. We further investigated
      the clinical impact of CXCL10 and found circulating and hepatic CXCL10 levels
      were significantly higher in human NASH. Importantly, the circulating CXCL10
      level was correlated with the degree of lobular inflammation and was an
      independent risk factor for NASH patients. CONCLUSIONS: We demonstrate for the
      first time that CXCL10 plays a pivotal role in the pathogenesis of experimental
      steatohepatitis. CXCL10 maybe a potential non-invasive biomarker for NASH
      patients.

PMID- 25048952
TI  - Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis
      undergoing an elective procedure.
AB  - BACKGROUND & AIMS: This is a phase II multicentre study to investigate the
      efficacy and safety of avatrombopag (E5501), an investigational second-generation
      thrombopoietin receptor agonist, administered one week prior to elective
      procedures in patients with thrombocytopenia secondary to cirrhosis. METHODS:
      Adults with cirrhosis and platelet counts ?10 to ?58*10(9)/L were randomized to
      placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3
      different doses (100mg loading dose followed by 20, 40, or 80 mg/day on days 2-7)
      of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2
      different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or
      20mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary
      end point was achievement of a platelet increase of ?20*10(9)/L from baseline and
      >50*10(9)/L at least once during days 4-8. RESULTS: A total of 130 patients were
      randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16,
      cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of
      treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of
      controls; a dose response was seen. Each avatrombopag regimen had a higher
      proportion of responders compared with their respective cohort placebo arms
      (p<0.01), except for the 100/40 mg group in cohort A (p=0.17). The most common
      adverse events were nausea, fatigue, and headache. One patient in the (100/80)
      avatrombopag group, without a Doppler assessment at screening was diagnosed with
      portal vein thrombosis during post-treatment follow-up. CONCLUSIONS: In this
      study avatrombopag was generally well-tolerated and increased platelet counts in
      patients with cirrhosis undergoing elective invasive procedures.

PMID- 25048953
TI  - Cyclophilin inhibition as potential therapy for liver diseases.
AB  - The cyclophilins are a group of proteins with peptidyl-prolyl isomerase enzymatic
      activity, localised in different cellular compartments and involved in a variety
      of functions related to cell metabolism and energy homeostasis, having enhanced
      expression in inflammation or malignancy. Cyclophilin A (CypA), the most
      abundantly expressed cyclophilin, is present mainly in the cytoplasm and is a
      host factor involved in the life cycle of multiple viruses. The extracellular
      fractions of CypA and CypB are potent pro-inflammatory mediators. CypD, located
      in mitochondria, is a key regulator of mitochondrial permeability transition
      pores, and is critical for necrotic cell death. Cyclosporines are the prototype
      cyclophilin inhibitors. Cyclic peptides, which bind and inhibit cyclophilins
      without having immunosuppressive properties, have been generated by chemical
      modifications of cyclosporin A. In addition, cyclophilin inhibitors that are
      structurally different from cyclosporines have been synthesized. The involvement
      of cyclophilins in the pathogenesis of different liver diseases has been
      established using both in vitro and in vivo investigations, thus indicating that
      cyclophilin inhibition may be of therapeutic benefit. This review summarises the
      evidence for potential therapeutic applications of non-immunosuppressive
      cyclophilin inhibitors, alone or in combination with other agents, in virus
      induced liver diseases like hepatitis C, B or Delta, liver inflammation and
      fibrosis, acetaminophen-induced liver toxicity and hepatocellular carcinoma. 

PMID- 25048954
TI  - Th17 response and its regulation in inflammatory upper airway diseases.
AB  - Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two widely prevalent
      inflammatory diseases in the upper airways. T cell immunity has been suggested to
      play an important pathogenic role in many chronic inflammatory diseases including
      inflammatory upper airway diseases. Inappropriate CD4(+) T cell responses,
      especially the dysregulation of the Th1/Th2 balance leading to excessive Th1 or
      Th2 cell activation, have been associated with allergic rhinitis and chronic
      rhinosinusitis. Nevertheless, recent studies suggest that IL-17A and IL-17A
      producing Th17 cell subset, a distinct pro-inflammatory CD4(+) T cell lineage,
      may also play an important role in the pathophysiology of inflammatory upper
      airway diseases. Th17 cells may promote both eosinophilic and neutrophilic
      inflammation in AR and CRS. In addition, a few, but accumulating evidence shows
      that the Th17 responses can be tightly regulated by endogenous and exogenous
      substances in the context of AR and CRS. This review discusses recent advances in
      our understanding of the expression and function of the Th17 response and its
      regulation in inflammatory upper airway diseases, and the perspective for future
      investigation and clinical utility. 

PMID- 25048955
TI  - Secondary prevention and health promotion after stroke: can it be enhanced?
AB  - The aim was to study if health outcome and secondary prevention were satisfactory
      1 year after stroke and if nurse-led interventions 3 months after stroke could
      have impact. Design was a randomized controlled open trial in a 1-year
      population. Primary outcome was health status 1 year after stroke. One month
      after stroke, survivors were randomized into intervention group (IG) with follow
      up by a specialist nurse (SN) after 3 months (n = 232), and control group (CG)
      with standard care (n = 227), all to be followed up 1 year after stroke. At the
      first follow-up, patients graded their health, replied to the EuroQol-5
      Dimensions (EQ-5D) health outcome questions, health problems were assessed, and
      supportive counseling was provided in the IG. Health problems requiring medical
      interventions were primarily referred to a general practitioner (GP). One year
      after stroke, 391 survivors were followed up. Systolic blood pressure (BP) had
      decreased in IG (n = 194) from median 140 to 135 (P = .05), but about half were
      above the limit 139 in both groups. A larger proportion (22%) had systolic BP
      >155 in the CG (n = 197) than in the IG (14%; P = .05). In the IG, 62% needed
      referrals compared with the 75% in the CG (P = .009). Forty percent in the IG and
      52.5% in the CG (P = .04) reported anxiety/depression. In the IG, 75% and 67% in
      the CG rated their general health as fairly good or very good (P = .05). Although
      nurse-led interventions could have some effect, the results were not optimal. A
      more powerful strategy could be closer collaboration between the SN and a stroke
      clinician, before referring to primary care.

PMID- 25048956
TI  - An application study of autohydrolysis pretreatment prior to poplar chemi
      thermomechanical pulping.
AB  - This study investigated the autohydrolysis pre-treatment prior to chemi
      thermomechanical pulping (CTMP) process including the effects of autohydrolysis
      pretreatment with a lower severity on characteristics of the autohydrolysis
      liquor and hydrolyzed chips. The intensity of autohydrolysis, characterized by
      the severity factor, increased from 1.76 to 3.54, the hydrolyzed chips yield
      decreased from 99.0% to 86.7% and the xylose extraction yield increased from 0.8%
      to 44.0%. The content of holocellulose, pentosan and acid soluble lignin remained
      in the hydrolyzed chips decreased dramatically with increasing the treatment
      severity. After the autohydrolysis pretreatment, the resultant poplar chemi
      thermomechanical pulp with a severity factor of 2.37 could obtain a 15.3 Nm/g
      tensile index, 58.6% ISO brightness and a 2.39 cm(3)/g bulk.

PMID- 25048957
TI  - Pre-treatment step with Leuconostoc mesenteroides or L. pseudomesenteroides
      strains removes furfural from Zymomonas mobilis ethanolic fermentation broth.
AB  - Furfural is an inhibitor of growth and ethanol production by Zymomonas mobilis.
      This study used a naturally occurring (not GMO) biological pre-treatment to
      reduce that amount of furfural in a model fermentation broth. Pre-treatment
      involved inoculating and incubating the fermentation broth with strains of
      Leuconostoc mesenteroides or Leuconostoc pseudomesenteroides. The Leuconostoc
      strains converted furfural to furfuryl alcohol without consuming large amounts of
      dextrose in the process. Coupling this pre-treatment to ethanolic fermentation
      reduced furfural in the broth and improved growth, dextrose uptake and ethanol
      formation. Pre-treatment permitted ethanol formation in the presence of 5.2 g L(
      1) furfural, which was otherwise inhibitive. The pre-treatment and presence of
      the Leuconostoc strains in the fermentation broth did not interfere with Z.
      mobilis ethanolic fermentation or the amounts of ethanol produced. The method
      suggests a possible technique for reducing the effect that furfural has on the
      production of ethanol for use as a biofuel.

PMID- 25048958
TI  - Combining microbial cultures for efficient production of electricity from
      butyrate in a microbial electrochemical cell.
AB  - Butyrate is an important product of anaerobic fermentation; however, it is not
      directly used by characterized strains of the highly efficient anode respiring
      bacteria (ARB) Geobacter sulfurreducens in microbial electrochemical cells. By
      combining a butyrate-oxidizing community with a Geobacter rich culture, we
      generated a microbial community which outperformed many naturally derived
      communities found in the literature for current production from butyrate and
      rivaled the highest performing natural cultures in terms of current density (~
      11A/m(2)) and Coulombic efficiency (~ 70%). Microbial community analyses support
      the shift in the microbial community from one lacking efficient ARB in the marine
      hydrothermal vent community to a community consisting of ~ 80% Geobacter in the
      anode biofilm. This demonstrates the successful production and adaptation of a
      novel microbial culture for generating electrical current from butyrate with high
      current density and high Coulombic efficiency, by combining two mixed microbial
      cultures containing complementing biochemical pathways.

PMID- 25048960
TI  - Ocean-scale patterns in community respiration rates along continuous transects
      across the Pacific Ocean.
AB  - Community respiration (CR) of organic material to carbon dioxide plays a
      fundamental role in ecosystems and ocean biogeochemical cycles, as it dictates
      the amount of production available to higher trophic levels and for export to the
      deep ocean. Yet how CR varies across large oceanographic gradients is not well
      known: CR is measured infrequently and cannot be easily sensed from space. We
      used continuous oxygen measurements collected by autonomous gliders to quantify
      surface CR rates across the Pacific Ocean. CR rates were calculated from changes
      in apparent oxygen utilization and six different estimates of oxygen flux based
      on wind speed. CR showed substantial spatial variation: rates were lowest in
      ocean gyres (mean of 6.93 mmol m(-3) d(-1)+/-8.0 mmol m(-3) d(-1) standard
      deviation in the North Pacific Subtropical Gyre) and were more rapid and more
      variable near the equator (8.69 mmol m(-3) d(-1)+/-7.32 mmol m(-3) d(-1) between
      10 degrees N and 10 degrees S) and near shore (e.g., 5.62 mmol m(-3) d(-1)+/-45.6
      mmol m(-3) d(-1) between the coast of California and 124 degrees W, and 17.0 mmol
      m(-3) d(-1)+/-13.9 mmol m(-3) d(-1) between 156 degrees E and the Australian
      coast). We examined how CR varied with coincident measurements of temperature,
      turbidity, and chlorophyll concentrations (a proxy for phytoplankton biomass),
      and found that CR was weakly related to different explanatory variables across
      the Pacific, but more strongly related to particular variables in different
      biogeographical areas. Our results indicate that CR is not a simple linear
      function of chlorophyll or temperature, and that at the scale of the Pacific, the
      coupling between primary production, ocean warming, and CR is complex and
      variable. We suggest that this stems from substantial spatial variation in CR
      captured by high-resolution autonomous measurements.

PMID- 25048959
TI  - Efficacy of ethanol ablation for thyroglossal duct cyst.
AB  - OBJECTIVE: Ethanol ablation has been known as an effective, easy, and safe
      treatment of cystic thyroid lesions. The objective of the present study was to
      evaluate efficacy of ethanol ablation as a minimally invasive management of
      thyroglossal duct cyst (TGDC). METHODS: Between January 2012 and July 2013, 9
      TGDC patients were diagnosed and treated with ethanol ablation. We evaluated the
      treatment outcomes with the change of volume reduction and the improvement of
      symptomatic and cosmetic complaints and complications. RESULTS: Initial mean
      tumor volume was 8.9 mL (range, 0.2-36.9 mL) in ultrasonography. The mean number
      of the treatment sessions was 1.7 (range, 1-3 sessions). At last follow-up, the
      mean volume of the treated thyroglossal duct cyst decreased significantly from
      8.9 mL to 1.9 mL (P = .019; volume reduction rate = 76.6%). Treatment success
      rate was 77.8% (7/9). Mean symptoms and cosmetic-grading scores improved from 5.2
      to 3.1 and from 5.3 to 3.1 (P = .062). No significant complications were observed
      during follow-up. CONCLUSION: Ethanol ablation is a feasible and convenient
      procedure without surgical scars and hospitalization for TGDC patients. Favorable
      outcomes can be achieved without significant complications.

PMID- 25048961
TI  - Development of an electrically driven molecular motor.
AB  - For molecules to be used as components in molecular machinery, methods are
      required that couple individual molecules to external energy sources in order to
      selectively excite motion in a given direction. While significant progress has
      been made in the construction of synthetic molecular motors powered by light and
      by chemical reactions, there are few experimental examples of electrically driven
      molecular motors. To this end, we pioneered the use of a new, stable and tunable
      molecular rotor system based on surface-bound thioethers to comprehensively study
      many aspects of molecular rotation. As biological molecular motors often operate
      at interfaces, our synthetic system is especially amenable to microscopic
      interrogation as compared to solution-based systems. Using scanning tunneling
      microscopy (STM) and density functional theory, we studied the rotation of
      surface-bound thioethers, which can be induced either thermally or by electrons
      from the STM tip in a two-terminal setup. Moreover, the temperature and electron
      flux can be adjusted to allow each rotational event to be monitored at the
      molecular scale in real time. This work culminated in the first experimental
      demonstration of a single-molecule electric motor, where the electrically driven
      rotation of a butyl methyl sulfide molecule adsorbed on a copper surface could be
      directionally biased. The direction and rate of the rotation are related to the
      chirality of both the molecule and the STM tip (which serves as the electrode),
      illustrating the importance of the symmetry of the metal contacts in atomic-scale
      electrical devices. 

PMID- 25048962
TI  - Assessment of mitochondrial DNA damage in little brown bats (Myotis lucifugus)
      collected near a mercury-contaminated river.
AB  - Historical discharges of Hg into the South River near the town of Waynesboro, VA,
      USA, have resulted in persistently elevated Hg concentrations in sediment,
      surface water, ground water, soil, and wildlife downstream of the discharge site.
      In the present study, we examined mercury (Hg) levels in in little brown bats
      (Myotis lucifugus) from this location and assessed the utility of a non
      destructively collected tissue sample (wing punch) for determining mitochondrial
      DNA (mtDNA) damage in Hg exposed bats. Bats captured 1 and 3 km from the South
      River, exhibited significantly higher levels of total Hg (THg) in blood and fur
      than those from the reference location. We compared levels of mtDNA damage using
      real-time quantitative PCR (qPCR) analysis of two distinct regions of mtDNA.
      Genotoxicity is among the many known toxic effects of Hg, resulting from direct
      interactions with DNA or from oxidative damage. Because it lacks many of the
      protective protein structures and repair mechanisms associated with nuclear DNA,
      mtDNA is more sensitive to the effects of genotoxic chemicals and therefore may
      be a useful biomarker in chronically exposed organisms. Significantly higher
      levels of damage were observed in both regions of mtDNA in bats captured 3 km
      from the river than in controls. However, levels of mtDNA damage exhibited weak
      correlations with fur and blood THg levels, suggesting that other factors may
      play a role in the site-specific differences.

PMID- 25048963
TI  - MCIDAS mutations result in a mucociliary clearance disorder with reduced
      generation of multiple motile cilia.
AB  - Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary
      clearance disorder. Affected persons suffer from recurrent infections of upper
      and lower airways because of highly reduced numbers of multiple motile
      respiratory cilia. Here we report recessive loss-of-function and missense
      mutations in MCIDAS-encoding Multicilin, which was shown to promote the early
      steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory
      epithelial cells carry only one or two cilia per cell, which lack ciliary
      motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia.
      Consistent with this finding, FOXJ1-regulating axonemal motor protein expression
      is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated
      known to cause RGMC, is also absent in MCIDAS mutant respiratory cells,
      consistent with its downstream activity. Thus, our findings identify Multicilin
      as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation,
      and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying
      RGMC. 

PMID- 25048964
TI  - Neuromodulatory control of a goal-directed decision.
AB  - Many cost-benefit decisions reduce to simple choices between approach or
      avoidance (or active disregard) to salient stimuli. Physiologically, critical
      factors in such decisions are modulators of the homeostatic neural networks that
      bias decision processes from moment to moment. For the predatory sea-slug
      Pleurobranchaea, serotonin (5-HT) is an intrinsic modulatory promoter of general
      arousal and feeding. We correlated 5-HT actions on appetitive state with its
      effects on the approach-avoidance decision in Pleurobranchaea. 5-HT and its
      precursor 5-hydroxytryptophan (5-HTP) augmented general arousal state and reduced
      feeding thresholds in intact animals. Moreover, 5-HT switched the turn response
      to chemosensory stimulation from avoidance to orienting in many animals. In
      isolated CNSs, bath application of 5-HT both stimulated activity in the feeding
      motor network and switched the fictive turn response to unilateral sensory nerve
      stimulation from avoidance to orienting. Previously, it was shown that increasing
      excitation state of the feeding network reversibly switched the turn motor
      network response from avoidance to orienting, and that 5-HT levels vary inversely
      with nutritional state. A simple model posits a critical role for 5-HT in control
      of the turn network response by corollary output of the feeding network. In it, 5
      HT acts as an intrinsic neuromodulatory factor coupled to nutritional status and
      regulates approach-avoidance via the excitation state of the feeding network.
      Thus, the neuromodulator is a key organizing element in behavioral choice of
      approach or avoidance through its actions in promoting appetitive state, in large
      part via the homeostatic feeding network. 

PMID- 25048966
TI  - Cytochrome P450 1A1 (CYP1A1) polymorphism and susceptibility to esophageal
      cancer: an updated meta-analysis of 27 studies.
AB  - Cytochrome P450 1A1 (CYP1A1) polymorphisms are known to play a crucial role in
      the development and metastasis of malignant diseases including esophageal cancer.
      However, the results of previous studies investigating the association between
      CYP1A1 polymorphisms and esophageal cancer risk have been inconsistent. This meta
      analysis of 27 eligible studies, encompassing 4,215 esophageal cancer cases and
      6,339 control subjects, pooled the odds ratios (ORs) with corresponding 95 %
      confidence intervals (95 % CI) to assess this association. The effects of
      ethnicity (Caucasian and Asian) and histopathology type (esophageal squamous cell
      carcinoma and esophageal adenocarcinoma) were considered in subgroup analyses. A
      significant association was observed between the CYP1A1 Ile/Val gene polymorphism
      and esophageal cancer in all of the genetic models (Ile/Val vs. Ile/Ile, OR =
      1.41, 95 % CI = 1.25-1.58; Val/Val vs. Ile/Ile, OR = 1.94, 95 % CI = 1.34-2.82;
      Ile/Val + Val/Val vs. Ile/Ile, OR = 1.49, 95 % CI = 1.33-1.66). The subgroup
      analysis based on ethnicity showed that the association between the CYP1A1
      Ile/Val polymorphism and esophageal cancer existed in Asian and Caucasian
      populations. However, no association was observed between the CYP1A1 MspI
      polymorphism and esophageal cancer in either subgroup or in the overall
      population. These results suggested that the CYP1A1 Ile/Val polymorphism was
      associated with an increased risk of esophageal cancer, whereas the CYP1A1 MspI
      polymorphism may not have increased susceptibility to esophageal cancer. Further
      studies are required to confirm these findings.

PMID- 25048967
TI  - Characterization of Lin-ALDH (bright) population using Ehrlich ascites tumor
      cells in mice.
AB  - Cancer stem cells (CSCs)/tumor initiating cells have been shown to exist in
      recent studies; however, it is challenging to isolate these cells. The latest
      evidence suggests that elevated aldehyde dehydrogenase (ALDH) activity is a
      hallmark of CSCs. In this study, mice implanted with Ehrlich ascites tumor (EAT)
      cells were used to isolate cancer stem cells. Femoral bone marrow aspirations
      were performed 15 days after the injection of EAT cells and Lin(-)ALDH(bright)
      and Lin(-)ALDH(low) cell populations were isolated. Lin(-)ALDH(bright) cells
      isolated from EAT-bearing mice accounted for 11.08 +/- 10.52 % of all the Lin(-)
      cell population. Analysis of hematopoietic stem cell markers showed that Sca-1, c
      kit, and CD38 were expressed higher in the Lin(-)ALDH(bright) population compared
      with Lin(-)ALDH(low). The Lin(-)ALDH(bright) population expressed P-glycoprotein,
      a product of the multidrug resistance (MDR) gene. P-gp activity measured by
      rhodamine 123 (Rh123) and blocked by verapamil. Among the cells treated with
      doxorubicin for 48 h, the Lin(-)ALDH(bright) cell groups were more resistant and
      had higher overexpression of Bcl-2 protein than Lin(-)ALDH(low).

PMID- 25048968
TI  - Association of functional polymorphism at the miR-502-binding site in the 3'
      untranslated region of the SETD8 gene with risk of childhood acute lymphoblastic
      leukemia, a preliminary report.
AB  - MicroRNAs (miRNAs), a class of non-coding RNAs, bind to the 3' untranslated
      regions (UTRs) of mRNAs, where they interfere with translation of genes and are
      implicated in the pathogenesis of diverse diseases. In the present study, we
      evaluate the impact of rs16917496 polymorphism within the miR-502 miRNA seed
      region at the 3'UTR of SEDT8 on childhood acute lymphoblastic leukemia (ALL).
      This case-control study was done on 75 ALL and 115 healthy children. Genotyping
      of rs16917496 C/T polymorphism was performed using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). The results showed that CT
      as well as CT + TT decreased the risk of ALL in comparison with CC genotype (odds
      ratio (OR) = 0.29, 95 % confidence intervals (95 % CI) = 0.11-0.78, P = 0.014 and
      OR = 0.31, 95 % CI = 0.12-0.82, P = 0.016, respectively). Our results
      demonstrated that SETD8 rs16917496 C/T polymorphism was associated with decreased
      risk of developing pediatric ALL in Zahedan, southeast Iran. Larger studies with
      different ethnicities are desired to validate our findings.

PMID- 25048969
TI  - Diagnostic tests based on gene expression profile in breast cancer: from
      background to clinical use.
AB  - Breast cancer is a complex disease with heterogeneous presentation and clinical
      course. The last decade has witnessed the development, commercialization, and
      increasing use of multigene assays, designed to support physicians and patients
      in clinical decision making in early-stage breast cancer. These include Oncotype
      DX(r), MammaPrint(r), and ProsignaTM assays. The assays differ in the
      technological platforms used for assessment of gene expression, in the number of
      genes and in the specific genes that are being tested, in the patient populations
      used for their development and validation, and in their clinical utility. This
      review focuses on these three commercialized assays, their development,
      validation, and clinical utility. The review also addresses ongoing prospective
      trials investigating these assays and health-economic considerations relating to
      their use.

PMID- 25048971
TI  - The active role of vitamin C in mammalian iron metabolism: much more than just
      enhanced iron absorption!
AB  - Ascorbate is a cofactor in numerous metabolic reactions. Humans cannot synthesize
      ascorbate owing to inactivation of the gene encoding the enzyme l-gulono-gamma
      lactone oxidase, which is essential for ascorbate synthesis. Accumulating
      evidence strongly suggests that in addition to the known ability of dietary
      ascorbate to enhance nonheme iron absorption in the gut, ascorbate within
      mammalian systems can regulate cellular iron uptake and metabolism. Ascorbate
      modulates iron metabolism by stimulating ferritin synthesis, inhibiting lysosomal
      ferritin degradation, and decreasing cellular iron efflux. Furthermore, ascorbate
      cycling across the plasma membrane is responsible for ascorbate-stimulated iron
      uptake from low-molecular-weight iron-citrate complexes, which are prominent in
      the plasma of individuals with iron-overload disorders. Importantly, this iron
      uptake pathway is of particular relevance to astrocyte brain iron metabolism and
      tissue iron loading in disorders such as hereditary hemochromatosis and beta
      thalassemia. Recent evidence also indicates that ascorbate is a novel modulator
      of the classical transferrin-iron uptake pathway, which provides almost all iron
      for cellular demands and erythropoiesis under physiological conditions. Ascorbate
      acts to stimulate transferrin-dependent iron uptake by an intracellular reductive
      mechanism, strongly suggesting that it may act to stimulate iron mobilization
      from the endosome. The ability of ascorbate to regulate transferrin iron uptake
      could help explain the metabolic defect that contributes to ascorbate-deficiency
      induced anemia. 

PMID- 25048970
TI  - Oxidized LDL lipids increase beta-amyloid production by SH-SY5Y cells through
      glutathione depletion and lipid raft formation.
AB  - Elevated total cholesterol in midlife has been associated with increased risk of
      dementia in later life. We have previously shown that low-density lipoprotein
      (LDL) is more oxidized in the plasma of dementia patients, although total
      cholesterol levels are not different from those of age-matched controls. beta
      Amyloid (Abeta) peptide, which accumulates in Alzheimer disease (AD), arises from
      the initial cleavage of amyloid precursor protein by beta-secretase-1 (BACE1).
      BACE1 activity is regulated by membrane lipids and raft formation. Given the
      evidence for altered lipid metabolism in AD, we have investigated a mechanism for
      enhanced Abeta production by SH-SY5Y neuronal-like cells exposed to oxidized LDL
      (oxLDL). The viability of SH-SY5Y cells exposed to 4MUg oxLDL and 25uM 27
      hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not
      proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the
      ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at
      sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was
      associated with an increase in acid sphingomyelinase (ASMase) activity and lipid
      raft formation, which could be inhibited by the ASMase inhibitor desipramine.
      27OH-C and total lipids from LDL and oxLDL independently increased Abeta
      production by SH-SY5Y cells, and Abeta accumulation could be inhibited by
      desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL
      lipids and 27OH-C can drive Abeta production by GSH depletion, ASMase-driven
      membrane remodeling, and BACE1 activation in neuronal cells.

PMID- 25048972
TI  - Commercial Lysogeny Broth culture media and oxidative stress: a cautious tale.
AB  - Lysogeny Broth (LB), most often misnamed Luria-Bertani medium, ranks among the
      most commonly used growth media in microbiology. Surprisingly, we observed that
      oxidative levels vary with the commercial origin of the LB ready to use powder.
      Indeed, growth on solid media of Escherichia coli and Salmonella derivatives
      lacking antioxidative stress defenses, such as oxyR mutant devoid of the H2O2
      sensing transcriptional activator or Hpx(-) strains lacking catalases and
      peroxidases, exhibit different phenotypes on LB-Sigma or LB-Difco. Using gene
      fusion and exogenously added catalase, we found that LB-Sigma contains higher
      levels of H2O2 than LB-Difco. Also we observed differences in population counts
      of 82 clinical and environmental isolates of E. coli, depending on the LB used.
      Further investigations revealed a significant influence of the commercial origin
      of agar as well. Besides being a warning to the wide population of LB users, our
      observations provide researchers in the oxidative stress field with a tool to
      appreciate the severity of mutations in antioxidative stress defenses. 

PMID- 25048974
TI  - When doctors and parents disagree: a recent example of morally appropriate
      collaboration between parents, doctors and the court.

PMID- 25048973
TI  - DNA double-strand breaks activate ATM independent of mitochondrial dysfunction in
      A549 cells.
AB  - Excessive nuclear or mitochondrial DNA damage can lead to mitochondrial
      dysfunction, decreased energy production, and increased generation of reactive
      oxygen species (ROS). Although numerous cell signaling pathways are activated
      when cells are injured, the ataxia telangiectasia mutant (ATM) protein has
      emerged as a major regulator of the response to both mitochondrial dysfunction
      and nuclear DNA double-strand breaks (DSBs). Because mitochondrial dysfunction is
      often a response to excessive DNA damage, it has been difficult to determine
      whether nuclear and/or mitochondrial DNA DSBs activate ATM independent of
      mitochondrial dysfunction. In this study, mitochondrial and nuclear DNA DSBs were
      generated in the A549 human lung adenocarcinoma cell line by infecting with
      retroviruses expressing the restriction endonuclease PstI fused to a
      mitochondrial targeting sequence (MTS) or nuclear localization sequence (NLS) and
      a hemagglutinin antigen epitope tag (HA). Expression of MTS-PstI-HA or NLS-PstI
      HA activated the DNA damage response defined by phosphorylation of ATM, the tumor
      suppressor protein p53 (TP53), KRAB-associated protein (KAP)-1, and structural
      maintenance of chromosomes (SMC)-1. Phosphorylated ATM and SMC1 were detected in
      nuclear fractions, whereas phosphorylated TP53 and KAP1 were detected in both
      mitochondrial and nuclear fractions. PstI also enhanced expression of the cyclin
      dependent kinase inhibitor p21 and inhibited cell growth. This response to DNA
      damage occurred in the absence of detectable mitochondrial dysfunction and excess
      production of ROS. These findings reveal that DNA DSBs are sufficient to activate
      ATM independent of mitochondrial dysfunction and suggest that the activated form
      of ATM and some of its substrates are restricted to the nuclear compartment,
      regardless of the site of DNA damage.

PMID- 25048975
TI  - Bounded agency in humanitarian settings: a qualitative study of adherence to
      antiretroviral therapy among refugees situated in Kenya and Malaysia.
AB  - HIV-positive refugees confront a variety of challenges in accessing and adhering
      to antiretroviral therapy (ART) and attaining durable viral suppression; however,
      there is little understanding of what these challenges are, how they are
      navigated, or how they may differ across humanitarian settings. We sought to
      document and examine accounts of the threats, barriers and facilitators
      experienced in relation to HIV treatment and care and to conduct comparisons
      across settings. We conducted semi-structured interviews among a purposive sample
      of 14 refugees attending a public, urban HIV clinic in Kuala Lumpur, Malaysia
      (July-September 2010), and 12 refugees attending a camp-based HIV clinic in
      Kakuma, Kenya (February-March 2011). We used framework methods and between-case
      comparison to analyze and interpret the data, identifying social and
      environmental factors that influenced adherence. The multiple issues that
      threatened adherence to antiretroviral therapy or precipitated actual adherence
      lapses clustered into three themes: "migration", "insecurity", and "resilience".
      The migration theme included issues related to crossing borders and integrating
      into treatment systems upon arrival in a host country. Challenges related to
      crossing borders were reported in both settings, but threats pertaining to
      integration into, and navigation of, a new health system were exclusive to the
      Malaysian setting. The insecurity theme included food insecurity, which was most
      commonly reported in the Kenyan setting; health systems insecurity, reported in
      both settings; and emotional insecurity, which was most common in the Kenyan
      setting. Resilient processes were reported in both settings. We drew on the
      concept of "bounded agency" to argue that, despite evidence of personal and
      community resilience, these processes were sometimes insufficient for overcoming
      social and environmental barriers to adherence. In general, interventions might
      aim to bolster individuals' range of action with targeted support that bolsters
      resilient processes. Specific interventions are needed to address locally-based
      food and health system insecurities. 

PMID- 25048976
TI  - MicroRNAs in bile vesicles: finding a trade-off for biomarker discovery.

PMID- 25048977
TI  - Piscine reovirus in wild and farmed salmonids in British Columbia, Canada: 1974
      2013.
AB  - Piscine reovirus (PRV) was common among wild and farmed salmonids in British
      Columbia, western Canada, from 1987 to 2013. Salmonid tissues tested for PRV by
      real-time rRT-PCR included sections from archived paraffin blocks from 1974 to
      2008 (n = 363) and fresh-frozen hearts from 2013 (n = 916). The earliest PRV
      positive sample was from a wild-source steelhead trout, Oncorhynchus mykiss
      (Walbaum), from 1977. By histopathology (n = 404), no fish had lesions diagnostic
      for heart and skeletal muscle inflammation (HSMI). In some groups,
      lymphohistiocytic endocarditis affected a greater proportion of fish with PRV
      than fish without PRV, but the range of Ct values among affected fish was within
      the range of Ct values among unaffected fish. Also, fish with the lowest PRV Ct
      values (18.4-21.7) lacked endocarditis or any other consistent lesion. From 1987
      to 1994, the proportion of PRV positives was not significantly different between
      farmed Atlantic salmon, Salmo salar L. (44% of 48), and wild-source salmonids
      (31% of 45). In 2013, the proportion of PRV positives was not significantly
      different between wild coho salmon, Oncorhynchus kisutch (Walbaum), sampled from
      British Columbia (5.0% of 60) or the reference region, Alaska, USA (10% of 58).

PMID- 25048978
TI  - How to image patients with spine pain.
AB  - Different radiological methods play an important role in the work-up of patients
      complaining of spine pain. Depending on the symptoms and the suspected underlying
      etiology different methods are selected. In the following presentation we briefly
      present the different radiological and magnetic resonance tomography methods that
      are at hand, give some guidance in which method to use, and present the typical
      imaging findings in some of the most common conditions that presents with spine
      pain. 

PMID- 25048979
TI  - Negative predictive value of multiparametric MRI for prostate cancer detection:
      outcome of 5-year follow-up in men with negative findings on initial MRI studies.
AB  - OBJECTIVE: To assess the clinical negative predictive value (NPV) of
      multiparametric MRI (mp-MRI) for prostate cancer in a 5-year follow-up. MATERIALS
      AND METHODS: One hundred ninety-three men suspected of harboring prostate cancer
      with negative MRI findings were included. Patients with positive transrectal
      ultrasound (TRUS)-guided biopsy findings were defined as false-negative. Patients
      with negative initial TRUS-guided biopsy findings were followed up and only
      patients with negative findings by digital rectal examination, MRI, and repeat
      biopsy and no increase in PSA at 5-year follow-up were defined as "clinically
      negative". The clinical NPV of mp-MRI was calculated. For quantitative analysis,
      mean signal intensity on T2-weighted images and the mean apparent diffusion
      coefficient value on ADC maps of the initial MRI studies were compared between
      peripheral-zone (PZ) cancer and the normal PZ based on pathologic maps of
      patients who had undergone radical prostatectomy. RESULTS: The clinical NPV of mp
      MRI was 89.6% for significant prostate cancer. Small cancers, prostatitis, and
      benign prostatic hypertrophy masking prostate cancer returned false-negative
      results. Quantitative analysis showed that there was no significant difference
      between PZ cancer and the normal PZ. CONCLUSION: The mp-MRI revealed a high
      clinical NPV and is a useful tool to rule out clinically significant prostate
      cancer before biopsy.

PMID- 25048980
TI  - A case of advanced lung cancer with malignant pericardial effusion treated by
      intrapericardial Cinobufacini injection instillation.
AB  - Malignant pericardial effusion is one of the severe complications in advanced
      lung cancer patients, seriously affecting the patient's cardiopulmonary function
      and even life. Pericardial drainage and instillation of anti-neoplastic drugs in
      the pericardial cavity seems to offer the best chance of controlling pericardial
      effusion. We reported a case concerning treatment of a 63-year-old man in
      advanced lung cancer with a large amount of pericardial effusion. We utilized
      pericardium puncture and drainage combined with instillation of Cinobufacini
      injection in the pericardial cavity to treat pericardial effusion. After
      treatment with Cinobufacini injection for two weeks, the patient was followed up
      in one month to assess effectiveness, quality of life, and safety. We found that
      the cardiac tamponade symptoms such as difficult breathing, chest distress, and
      palpitations were significantly relieved. The patient's quality of life was
      effectively improved with KPS scores increased. We also found that the levels of
      tumor marker CA-125 in the pericardial effusion decreased (from 340.80 U/mL to
      34.85 U/mL) and pericardium B ultrasound showed that the quantity of pericardial
      effusion reduced significantly (from 2.5 cm to 0.6 cm). Furthermore, there were
      little gastrointestinal adverse reactions and myelosuppression in the patient
      after instillation of the Cinobufacini injection. Taken together, this provides a
      new way for treating cancerous pericardial effusion, especially for patients who
      cannot tolerate instillation of chemotherapy drugs, and is worthwhile to carry
      out more standardized studies in the future. 

PMID- 25048981
TI  - Outcomes after endovascular or open repair for degenerative descending thoracic
      aortic aneurysm using linked hospital data.
AB  - BACKGROUND: The population-based effectiveness of thoracic endovascular aortic
      repair (TEVAR) versus open surgery for descending thoracic aortic aneurysm
      remains in doubt. METHODS: Patients aged over 50 years, without a history of
      aortic dissection, undergoing repair of a thoracic aortic aneurysm between 2006
      and 2011 were assessed using mortality-linked individual patient data from
      Hospital Episode Statistics (England). The principal outcomes were 30-day
      operative mortality, long-term survival (5 years) and aortic-related
      reinterventions. TEVAR and open repair were compared using crude and
      multivariable models that adjusted for age and sex. RESULTS: Overall, 759
      patients underwent thoracic aortic aneurysm repair, mainly for intact aneurysms
      (618, 81.4 per cent). Median ages of TEVAR and open cohorts were 73 and 71 years
      respectively (P < 0.001), with more men undergoing TEVAR (P = 0.004). For intact
      aneurysms, the operative mortality rate was similar for TEVAR and open repair
      (6.5 versus 7.6 per cent; odds ratio 0.79, 95 per cent confidence interval (c.i.)
      0.41 to 1.49), but the 5-year survival rate was significantly worse after TEVAR
      (54.2 versus 65.6 per cent; adjusted hazard ratio 1.45, 95 per cent c.i. 1.08 to
      1.94). After 5 years, aortic-related mortality was similar in the two groups, but
      cardiopulmonary mortality was higher after TEVAR. TEVAR was associated with more
      aortic-related reinterventions (23.1 versus 14.3 per cent; adjusted HR 1.70, 95
      per cent c.i. 1.11 to 2.60). There were 141 procedures for ruptured thoracic
      aneurysm (97 TEVAR, 44 open), with TEVAR showing no significant advantage in
      terms of operative mortality. CONCLUSION: In England, operative mortality for
      degenerative descending thoracic aneurysm was similar after either TEVAR or open
      repair. Patients who had TEVAR appeared to have a higher reintervention rate and
      worse long-term survival, possibly owing to cardiopulmonary morbidity and other
      selection bias.

PMID- 25048982
TI  - Biocontrolled formal inversion or retention of L-alpha-amino acids to enantiopure
      (R)- or (S)-hydroxyacids.
AB  - Natural L-alpha-amino acids and L-norleucine were transformed to the
      corresponding alpha-hydroxy acids by formal biocatalytic inversion or retention
      of absolute configuration. The one-pot transformation was achieved by a
      concurrent oxidation reduction cascade in aqueous media. A representative panel
      of enantiopure (R)- and (S)-2-hydroxy acids possessing aliphatic, aromatic and
      heteroaromatic moieties were isolated in high yield (67-85 %) and enantiopure
      form (>99 % ee) without requiring chromatographic purification. 

PMID- 25048983
TI  - Alteration of interaction between astrocytes and neurons in different stages of
      diabetes: a nuclear magnetic resonance study using [1-(13)C]glucose and [2
      (13)C]acetate.
AB  - Increasing evidence has shown that the brain is a site of diabetic end-organ
      damage. This study investigates cerebral metabolism and the interactions between
      astrocytes and neurons at different stages of diabetes to identify the potential
      pathogenesis of diabetic encephalopathy. [1-(13)C]glucose or [2-(13)C]acetate is
      infused into 1- and 15-week diabetic rats, the brain extracts of which are
      analyzed by using (1)H and (13)C magnetic resonance spectroscopy. The (13)C
      labeling pattern and enrichment of cerebral metabolites are also investigated.
      The increased (13)C incorporation in the glutamine, glutamate, and gamma
      aminobutyric acid carbons from [2-(13)C]acetate suggests that the astrocytic
      mitochondrial metabolism is enhanced in 1-week diabetic rats. By contrast, the
      decreased labeling from [1-(13)C]glucose reflected that the neuronal
      mitochondrial metabolism is impaired. As diabetes developed to 15 weeks,
      glutamine and glutamate concentrations significantly decreased. The increased
      labeling of glutamine C4 but unchanged labeling of glutamate C4 from [2
      (13)C]acetate suggests decreased astrocyte supply to the neurons. In addition,
      the enhanced pyruvate recycling pathway manifested by the increased lactate C2
      enrichment in 1-week diabetic rats is weakened in 15-week diabetic rats. Our
      study demonstrates the overall metabolism disturbances, changes in specific
      metabolic pathways, and interaction between astrocytes and neurons during the
      onset and development of diabetes. These results contribute to the mechanistic
      understanding of diabetes pathogenesis and evolution. 

PMID- 25048985
TI  - Conjugated polymer dots for ultra-stable full-color fluorescence patterning.
AB  - Stable full-color fluorescence patterning are achieved by multicolor polymer-dot
      inks. The fluorescent patterns show extraordinary stability upon various
      treatments, offering a superior combination of bright fluorescence, excellent
      photostability, chemical resistance, and eco-friendship. 

PMID- 25048984
TI  - Endoplasmic reticulum stress: relevance and therapeutics in central nervous
      system diseases.
AB  - Endoplasmic reticulum (ER) stress plays an important role in a range of
      neurological disorders, such as neurodegenation diseases, cerebral ischemia,
      spinal cord injury, sclerosis, and diabetic neuropathy. Protein misfolding and
      accumulation in the ER lumen initiate unfolded protein response in energy-starved
      neurons which are relevant to toxic effects. In neurological disorders, such as
      Alzheimer's disease, Parkinson's disease, and Huntington's disease, ER
      dysfunction is well recognized, but the mechanisms remain unclear. In stroke and
      ischemia, spinal cord injury, and amyotrophic lateral sclerosis, chronic
      activation of ER stress is considered as main pathogeny which causes neuronal
      disorders. By targeting components of these ER signaling responses, to explore
      clinical treatment strategies or new drugs in CNS neurological diseases might
      become possible and valuable in the future. 

PMID- 25048986
TI  - Data extraction and reporting strategies of studies assessing non-central corneal
      thickness by Pentacam: a review.
AB  - PURPOSE: To review data extraction strategies for the reporting of non-central
      corneal thickness with the Pentacam system. METHODS: Using predefined search
      terms, the electronic National Institutes of Health database (PubMed) was
      searched for studies assessing non-central corneal thickness using the Pentacam
      instrument. The article titles of the search results were screened for relevance.
      The abstracts of papers with appropriate titles were retrieved and read. Articles
      with relevant abstracts were obtained and read in full. The reference list of
      each article was hand searched to identify further studies. Articles reporting
      central corneal thickness only were excluded. RESULTS: Seventeen peer-reviewed
      studies were identified. Considerable differences in data extraction and
      reporting of non-central corneal thickness were noted, with non-central
      pachymetry being assessed at locations between 1.5 and 5.0mm away from the
      centre. The terminology used to describe non-central pachymetry was inconsistent.
      Ring-averaged and single point pachymetry data have been reported. Ring-averaged
      pachymetry may obscure considerable regional variability in corneal thickness.
      CONCLUSIONS: The use of different data extraction and reporting strategies can
      obscure regional corneal thickness asymmetries. This may influence the monitoring
      of corneal crosslinking outcomes, the interpretation of corneal swelling in
      contact lens studies and the clinical decision-making in preoperative assessments
      of refractive surgery patients. For the reliable identification of regional
      corneal thickness variations point-pachymetry data appears to be preferable over
      ring-averaged pachymetry.

PMID- 25048987
TI  - Effects of motives on reactions to safe sun messages.
AB  - We investigated whether appearance motive for sun exposure, which strongly
      predicts exposure behaviour, would predict reactions to safe sun messages. In a
      survey with an embedded experiment, 245 individuals completed measures of
      motives, read a safe sun message framed by incentive (appearance/health), tone
      (directive/nondirective) and valence (gain/loss), then completed measures of
      reactions. For participants high in appearance motive, an appearance-nondirective
      message was most persuasive. Regardless of individual's appearance motive,
      appearance messages produced lower reactance if phrased using nondirective
      language. To maximise persuasion and minimise reactance in individuals most
      motivated to sun expose, safe sun messages should focus on appearance using
      nondirective language. 

PMID- 25048988
TI  - Comprehensive identification of MHC class II alleles in a cohort of Chinese
      rhesus macaques.
AB  - Rhesus macaque is a very important animal model for various human diseases,
      especially for AIDS and vaccine research. The susceptibility and/or resistance to
      some of these diseases are related to the major histocompatibility complex (MHC).
      To gain insight into the MHC background and to facilitate the experimental use of
      Chinese rhesus macaques, Mamu-DPB1, Mamu-DQB1, and Mamu-DRB alleles were
      investigated in 30 Chinese rhesus macaques through gene cloning and sequencing. A
      total of 66 alleles were identified in this study, including 14 Mamu-DPB1, 20
      Mamu-DQB1, and 30 Mamu-DRB alleles as well as 2 high-frequency Mamu-DPB1 alleles.
      Interestingly, one of the high-frequency Mamu-DPB1 alleles had been undocumented
      in earlier studies. Eleven of the other alleles, including four Mamu-DPB1, three
      Mamu-DQB1, and four Mamu-DRB alleles were also novel. Importantly, like MHC-DRB,
      more than two Mamu-DPB1 sequences per animal were detected in 13 monkeys, which
      suggested that they might represent gene duplication. Our data also indicated
      quite a few differences in the distribution of MHC class II alleles between the
      Chinese rhesus macaques and the previously reported Indian rhesus macaques. To
      our knowledge, our results revealed comprehensively the combination of MHC II
      alleles. This information will not only promote the understanding of Chinese
      rhesus macaque MHC polymorphism but will also facilitate the use of Chinese
      rhesus macaques in studies of human disease. 

PMID- 25048989
TI  - Ruthenium sensitizers having an ortho-dicarboxyl group as an anchoring unit for
      dye-sensitized solar cells: synthesis, photo- and electrochemical properties, and
      adsorption behavior to the TiO2 surface.
AB  - A novel ruthenium sensitizer ((TBA)[Ru(3',4'-dicarboxyterpyridine)(NCS)3], TBA =
      tetrabutylammonium, TUS-28) has been synthesized as an improved model sensitizer
      for (TBA)[Ru(4'-(3,4-dicarboxyphenyl)terpyridine)(NCS)3] (TUS-20). The molar
      absorptivity of TUS-28 in the whole visible region was smaller than that of TUS
      20 due to the absence of the phenyl ring at the terpyridine ligand. On the other
      hand, the energy levels of HOMO and LUMO of TUS-28 were still suitable for
      effective electron transfer reactions in dye-sensitized solar cells (DSCs). TUS
      28 did not show a superior adsorptivity to the TiO2 surface just like TUS-20,
      even though TUS-28 has an ortho-dicarboxyl group which is reported to be an
      efficient anchoring unit. ATR-IR measurements revealed that both carboxyl groups
      of TUS-28 participate in binding to the TiO2 surface just like TUS-20. Therefore,
      steric hindrance between the hydrogen atom at the 4-position of 3',4'
      dicarboxyterpyridine and the OH group at the TiO2 surface seems to retard the
      rapid adsorption, and to weaken the binding strength of TUS-28. The DSC with TUS
      28 showed 8.2% conversion efficiency, which is higher than that of TUS-20 (7.5%).
      The J(sc) value of the DSC with TUS-28 was larger than that of TUS-20 even though
      the amount of dye adsorption of TUS-28 was smaller than that of TUS-20. A more
      effective electron injection reaction is considered to contribute mainly to the
      efficiency improvement of TUS-28 since the path length of the electron injection
      from TUS-28 to the conduction band of the TiO2 is shorter than that of TUS-20 due
      to the absence of the phenyl ring.

PMID- 25048990
TI  - Inflammation and vitamin D: the infection connection.
AB  - INTRODUCTION: Inflammation is believed to be a contributing factor to many
      chronic diseases. The influence of vitamin D deficiency on inflammation is being
      explored but studies have not demonstrated a causative effect. METHODS: Low serum
      25(OH)D is also found in healthy persons exposed to adequate sunlight. Despite
      increased vitamin D supplementation inflammatory diseases are increasing. The
      current method of determining vitamin D status may be at fault. The level of
      25(OH)D does not always reflect the level of 1,25(OH)2D. Assessment of both
      metabolites often reveals elevated 1,25(OH)2D, indicating abnormal vitamin D
      endocrine function. FINDINGS: This article reviews vitamin D's influence on the
      immune system, examines the myths regarding vitamin D photosynthesis, discusses
      ways to accurately assess vitamin D status, describes the risks of
      supplementation, explains the effect of persistent infection on vitamin D
      metabolism and presents a novel immunotherapy which provides evidence of an
      infection connection to inflammation. CONCLUSION: Some authorities now believe
      that low 25(OH)D is a consequence of chronic inflammation rather than the cause.
      Research points to a bacterial etiology pathogenesis for an inflammatory disease
      process which results in high 1,25(OH)2D and low 25(OH)D. Immunotherapy, directed
      at eradicating persistent intracellular pathogens, corrects dysregulated vitamin
      D metabolism and resolves inflammatory symptoms.

PMID- 25048991
TI  - NLRP3 inflammasome activation and interleukin-1beta release in macrophages
      require calcium but are independent of calcium-activated NADPH oxidases.
AB  - OBJECTIVE AND DESIGN: We studied the involvement of calcium and calcium-activated
      NADPH oxidases in NLRP3 inflammasome activation and IL-1beta release to better
      understand inflammasome signaling in macrophages. MATERIAL OR SUBJECTS: Human
      volunteer blood donors were recruited to isolate monocytes to differentiate them
      into macrophages. Wild-type or DUOX1-deficient C57/B6 mice were used to prepare
      bone marrow-derived macrophages. TREATMENT: Murine or human macrophages were
      treated in vitro with NLRP3 inflammasome agonists (ATP, silica crystals) or
      calcium agonists (thapsigargin, ionomycin) in calcium-containing or calcium-free
      medium. METHODS: Intracellular calcium changes were followed by measuring FURA2
      based fluorescence. Gene expression changes were measured by quantitative real
      time PCR. Protein expression was assessed by western blotting. Enzymatic activity
      was measured by fluorescence caspase-1 activity assay. IL-1beta release was
      determined by ELISA. ELISA data were analyzed by ANOVA and Tukey's post hoc test.
      RESULTS: Our data show that calcium is essential for IL-1beta release in human
      macrophages. Increases in cytosolic calcium alone lead to IL-1beta secretion.
      Calcium removal blocks caspase-1 activation. Human macrophages express Duox1, a
      calcium-regulated NADPH oxidase that produces reactive oxygen species. However,
      Duox1-deficient murine macrophages show normal IL-1beta release. CONCLUSIONS:
      Human macrophage inflammasome activation and IL-1beta secretion requires calcium
      but does not involve NADPH oxidases.

PMID- 25048992
TI  - Embryo development, fetal growth and postnatal phenotype of eGFP lambs generated
      by lentiviral transgenesis.
AB  - Lentiviral technology has been recently proposed to generate transgenic farm
      animals more efficiently and easier than traditional techniques. The objective
      was to evaluate several parameters of lambs obtained by lentiviral transgenesis
      in comparison with non-transgenic counterparts. In vitro produced embryos were
      microinjected (TG group) at two-cell stage with a lentiviral construct containing
      enhanced green fluorescent protein (eGFP) gene, while embryos produced by in
      vitro fertilization (IVF group) or intrauterine insemination (IUI group) were not
      microinjected. Microinjection technique efficiently generated eight-cell
      transgenic embryos (97.4%; 114/117). Development rate on day 5 after
      fertilization was similar for TG (39.3%, 46/117) and IVF embryos (39.6%, 44/111).
      Pregnancy rate was detected in 50.0% (6/12) of recipient ewes with TG embryos, in
      46.7% (7/15) with IVF embryos, and in 65.0% (13/20) of IUI ewes (P = NS). Nine
      lambs were born in TG group, six lambs in IVF group, and 16 lambs in IUI group.
      All TG lambs (9/9) were GFP positive to real-time PCR and eight (88.9%) showed a
      strong and evident GFP expression in mucosae, eyes and keratin tissues. Fetal
      growth monitored every 15 day by ultrasonography did not show significant
      differences. Transgenic lambs neither differ in morphometric variables in
      comparison with non transgenic IVF lambs within 3 months after birth.
      Transmission of the transgene to the progeny was observed in green fluorescent
      embryos produced by IVF using semen from the TG founder lambs. In conclusion,
      this study demonstrates the high efficiency of lentiviral technology to produce
      transgenic sheep, with no clinic differences in comparison with non transgenic
      lambs.

PMID- 25048993
TI  - Two-dimensional measurement of tricuspid annular plane systolic excursion in
      children: can it substitute for an m-mode assessment?
AB  - BACKGROUND: Tricuspid annular plane systolic excursion measured by M-mode (MM
      TAPSE) has been validated as a marker of right ventricular systolic performance.
      A similar measurement by 2D imaging (2D-TAPSE) can be obtained. We sought to
      determine the correlation and strength of agreement between MM-TAPSE and 2D-TAPSE
      in children. METHODS: Echocardiographic studies performed for clinical
      indications were reviewed retrospectively. All consecutive subjects <=18 years of
      age were included. The cohort was divided into those with normal
      echocardiographic findings and those with disorders affecting the right
      ventricle. Digitally recorded images were analyzed for both MM-TAPSE and 2D
      TAPSE. Measurements of 2D-TAPSE were made in an apical four-chamber view, from
      the tricuspid valve annulus to a consistent point at the apex of the imaging
      sector at end-diastole and end-systole, with the difference representing the 2D
      TAPSE value. RESULTS: A total of 329 subjects (mean age 9.0 +/- 6.1 years) met
      entry criteria. Correlation coefficient between MM-TAPSE and 2D-TAPSE was 0.90.
      Bland-Altman analysis showed agreement between the two methods to be within 1.2
      +/- 2.6 mm (mean percentage difference of 6.5%). About 1 mm difference between MM
      TAPSE and 2D-TAPSE was consistently observed in all diagnostic subgroups, and
      across all age categories. CONCLUSION: MM-TAPSE and 2D-TAPSE correlate strongly,
      with 2D-TAPSE being consistently about 1 mm less than values obtained by the M
      mode technique. We conclude that 2D-TAPSE can provide a reliable alternative to
      MM-TAPSE to quantitatively measure right ventricular systolic function and may be
      especially useful in situations where retrospective comparisons are sought.

PMID- 25048994
TI  - Mortality risk factors in critical post-surgical patients treated using
      continuous renal replacement techniques.
AB  - OBJECTIVE: To determine the influence of demographics, medical, and surgical
      variables on 30-day mortality in patients who need continuous renal replacement
      therapy (CRRT). MATERIALS AND METHODS: A retrospective-following study was
      conducted using the data of 112 patients admitted to the postoperative intensive
      care unit who required CRRT, between August 2006 and August 2011, and followed-up
      for 30 days. The following information was collected: age, gender, history of
      HBP, DM, cardiovascular disease, and CKD, urgent surgery, surgical speciality,
      organic dysfunction according to the SOFA scale, the number of organs with
      dysfunction, use of mechanical ventilation, diagnostic and origin of sepsis, type
      of CRRT, and 30-day mortality. General linear models were used for estimating the
      strength of association (relative risk [RR], and 95% confidence interval [CI]
      between variables and 30-day mortality. RESULTS: In the univariant analysis, the
      following variables were identified as risk factors for 30-day mortality: age (RR
      1.04; 95% CI 1.01-1.06; P=.0005), and history of cardiovascular disease (RR 1.57;
      95% CI 1.02-2.41; P=.039). Among the variables included in the multivariable
      analysis (age, history of cardiovascular disease, sepsis, and number of organs
      with dysfunction), only age was identified as an independent risk factor for 30
      day mortality (RR 1.03; 95% CI 1.00-1.05; P=.007). CONCLUSION: Thirty-day
      mortality in postoperative, critically ill patients who require CRRT is high
      (41.07%). Age has been identified as an independent risk factor, with renal
      failure as the most common indication for the use of these therapies.

PMID- 25048995
TI  - [Is obesity a risk factor for complications, hospital admissions, and surgical
      cancellations in ambulatory surgery?].
AB  - OBJECTIVES: To determine the incidence of outcomes, unanticipated admissions and
      cancellations in patients operated in an Ambulatory surgery unit, and to
      establish the relationships with their body mass index (BMI). SUBJECTS AND
      METHODS: An observational descriptive prospective study was conducted in the
      Ambulatory surgery unit of the University Hospital Virgen del Rocio of Seville,
      on ASA I or II adult patients proposed for day case surgery with loco-regional or
      general anesthesia. A cohort of 1,088 patients was classified according to their
      body mass index into four groups: no obesity (BMI<30), obesity i (BMI 30-34.9),
      obesity ii (BMI 35-39.9), and morbid obesity iii (BMI 40-49.9). Postoperative
      outcomes (48h), inpatient admissions, and cancellations where calculated.
      RESULTS: The obesity ii (BMI 35-39.9) group showed a higher incidence of
      postoperative complications (7.69%), unplanned admissions (7.69%), and surgical
      cancellations (4.87%), doubling, at least, the incidence of adverse events of the
      other study groups, even when no significant difference was found. Outcomes where
      similar in all study groups. CONCLUSIONS: The results of this study suggest that
      moderate and severe obesity should be a risk factor for postoperative
      complications, unplanned admissions, and cancellations in outpatient surgery.
      Adequate patient selection and preoperative evaluation, as well as strategies for
      the prevention and control of the most frequents complications in obese patients
      are the key factors for their integration in major ambulatory surgery programs.

PMID- 25048996
TI  - [Is there an appropriate bispectral index for upper gastrointestinal endoscopy in
      spontaneous breathing in the pediatric patient?].
AB  - OBJECTIVE: The bispectral index (BIS) values that predict appropriate anesthetic
      level to perform an upper gastrointestinal endoscopy in spontaneous breathing are
      not well established in Pediatrics. The objective of this study is to determine
      whether it is possible to find an appropriate, less profound, BIS level in the
      pediatric patient that would enable an upper gastrointestinal endoscopy (UGE) to
      be performed in spontaneous breathing without causing gag reflex or motor
      response. MATERIAL AND METHOD: A prospective study was designed and included 61
      patients from 12-167 months old, and an ASAI-II who needed a diagnostic UGE. The
      study was conducted from October 2011 to March 2013. INTERVENTION: UGE performed
      with an anesthetic protocol using propofol. The vital signs measured were heart
      and respiratory rate, pulse oximetry, non-invasive blood pressure. The sedation
      level score (Ramsay scale) and BIS values were also measured. The first attempt
      was performed at BIS level 60-69, and this was not feasible, then the anesthetic
      was deepened and a second attempt made at BIS level 50-59. If this was still not
      possible a deeper anesthetic level was then achieved and a third attempt made at
      BIS level 45-49. Variables of interest were: effective BIS level (eBIS), BIS
      level at which UGE was performed without gag reflex or motor response; propofol
      total dose (mgkg(-1)), induction time (time from onset of sedation to effective
      start of UGE). A logistic regression analysis was performed to obtain an equation
      to estimate the possibility of UGE success. RESULTS: The distribution of the
      patient was: male 40%, female 60%, with 11 (18%) patients under 36 months. The
      statistical values are expressed as mean and standard deviation, with following
      results; age (months): 95.9+/-45.86; weight (kg): 30.5+/-14.68; effective BIS:
      56.41+/-4.63; induction time (minutes): 11.07+/-2.69; total propofol dose (per
      kg): 4.86+/-1.21. An additional intra-procedure propofol bolus was given in 38
      patients (62%), with 7/38 of them (18%) due to movement, and 31/38 (82%) due to
      BIS level increase. No statistical differences were found in effective BIS level
      between older and younger patients. CONCLUSIONS: According to the results, BIS
      levels below 59 predict UGE success, with 72.13% sensitivity and 88.06%
      specificity in the pediatric population studied.

PMID- 25048997
TI  - [Peroneal nerve injury: anesthesia is not always to blame].
AB  - We introduce a case report of a woman that was operated of foot surgery under
      locoregional anesthesia with an echo-guided peripheral sciatic-popliteal nerve
      block. As post operatory complication a peroneal nerve injury was noticed. We
      revised differential diagnosis of peripheral nerve block and therapeutic strategy
      we should take. In our case the finding was a high degree axonotmesis secondary
      to extrinsic compressure due to pneumatic tourniquet placed in the ankle used
      during surgery. There was no relationship with the anesthetic technique. 

PMID- 25048998
TI  - [Intraoperative anaphylaxis due to beta-lactams in a hypertensive patient on
      angiotensin ii receptor antagonists and beta-blockers].

PMID- 25048999
TI  - [Effect of priming solution and ultrafiltration on post-operative bleeding and
      blood transfusion in cardiac surgery. Randomized controlled trial].
AB  - OBJECTIVE: Assess the effectiveness of priming the extracorporeal circulation
      system with albumin-mannitol combined with ultrafiltration during extracorporeal
      circulation to reduce post-operative bleeding and transfusion requirements in
      heart surgery, as well as its impact on the fluid balance, coagulation and
      hematocrit parameters, re-operation for bleeding, ICU, and hospital length of
      stay. MATERIAL AND METHODS: A total of 134 patients scheduled for heart surgery
      were randomized to receive Ringer's lactate 1,500mL in the priming reservoir
      (group C), or mannitol 20% 250mL, albumin 20% 150mL and Ringer's lactate 1,100mL
      combined with ultrafiltration (group T). Bleeding volume, transfusions, fluid
      balance, coagulation, and hematology parameters were determined until 48h in the
      post-operative period. RESULTS: There was a reduction of postoperative bleeding
      in group T, 1,165+/-789mL vs 992+/-662mL (P=.17), and red blood cell concentrate
      transfusions, 694+/-843mL vs 413+/-605mL (P=.03). Intra-operative and post
      operative fluid balance was significantly less positive in group T, with an
      overall balance of 2,292+/-2,152mL vs 5,388+/-2,834mL (P<.001). There were higher
      values of hemoglobin and hematocrit, intraoperative (P<.001), on admission to ICU
      (P=.001), and at 6h (P=.05) in group T, and lower INR at 6h (P=.01) and 24h
      (P=.02). Re-operation rate and length of stay in ICU were higher in group C, but
      not statiscally significant. CONCLUSIONS: The priming of extracorporeal reservoir
      with mannitol, albumin, and Ringer's lactate, combined with ultrafiltration,
      significantly improves intra- and post-operative fluid balance, resulting in a
      reduction in blood transfusions, with no significant decrease in post-operative
      bleeding, re-operation bleeding rate, and length of stay in the ICU.

PMID- 25049000
TI  - [Improving the esthetic results and patient satisfaction in orthognatic surgery].
AB  - The objectives of dental and maxillary defect management have changed over the
      last decade. Occlusal improvement is required, but it is expected to come with a
      good esthetic result for patients, especially for adults, and mentioned or not
      preoperatively. Thus, the maxillofacial surgeon must include complementary data
      in his therapeutic scheme, beyond the one provided by the cephalometric analysis.
      This chapter was drafted in pluridisciplinary mode to this end. A psychological
      approach and post-operative satisfaction are crucial factors that were studied
      prospectively (MD Battini and Courtois) and are a part of this chapter. Esthetic
      labial standard are also described, based on the results of a retrospective study
      (MD Hardy, Laure and Goga). Doctor Belhaouari presents solutions to embellish
      lips with filling products, initially or later. Finally, the complementary
      surgical techniques that can be used during orthognatic surgery are listed:
      lipofilling, rhinoplasty, surgery of mandibular angles, apposition of piriform
      aperture. 

PMID- 25049001
TI  - Does increasing steps per day predict improvement in physical function and pain
      interference in adults with fibromyalgia?
AB  - OBJECTIVE: To examine the concurrent and predictive associations between the
      number of steps taken per day and clinical outcomes in patients with fibromyalgia
      (FM). METHODS: A total of 199 adults with FM (mean age 46.1 years, 95% women) who
      were enrolled in a randomized clinical trial wore a hip-mounted accelerometer for
      1 week and completed self-report measures of physical function (Fibromyalgia
      Impact Questionnaire-Physical Impairment [FIQ-PI], Short Form 36 [SF-36] health
      survey physical component score [PCS], pain intensity and interference (Brief
      Pain Inventory [BPI]), and depressive symptoms (Patient Health Questionnaire-8
      [PHQ-8]) as part of their baseline and followup assessments. Associations of
      steps per day with self-report clinical measures were evaluated from baseline to
      week 12 using multivariate regression models adjusted for demographic and
      baseline covariates. RESULTS: Study participants were primarily sedentary,
      averaging 4,019 +/- 1,530 steps per day. Our findings demonstrate a linear
      relationship between the change in steps per day and improvement in health
      outcomes for FM. Incremental increases on the order of 1,000 steps per day were
      significantly associated with (and predictive of) improvements in FIQ-PI, SF-36
      PCS, BPI pain interference, and PHQ-8 (all P < 0.05). Although higher step counts
      were associated with lower FIQ and BPI pain intensity scores, these were not
      statistically significant. CONCLUSION: Step count is an easily obtained and
      understood objective measure of daily physical activity. An exercise prescription
      that includes recommendations to gradually accumulate at least 5,000 additional
      steps per day may result in clinically significant improvements in outcomes
      relevant to patients with FM. Future studies are needed to elucidate the dose
      response relationship between steps per day and patient outcomes in FM.

PMID- 25049002
TI  - Isolated spontaneous dissection of a visceral artery: a rare cause of epigastric
      pain.
AB  - BACKGROUND: Isolated spontaneous dissection of the celiac trunk or superior
      mesenteric artery is rarely considered in patients with acute abdominal pain.
      However, with advances in computed tomography (CT) technology, more cases are
      being detected. PURPOSE: The aim of this study was to describe the clinical
      manifestation and the classical CT features of isolated spontaneous celiac trunk
      and superior mesenteric artery (SMA) dissection. MATERIAL AND METHODS: The
      records of seven patients were reviewed to assess demographic data, presenting
      symptoms, location of dissection, diagnostic modalities, imaging findings,
      complications, and treatment. RESULTS: Six patients were men. The average age was
      57 years (range, 44-80). Six had epigastric pain and one was asymptomatic. All
      were diagnosed by CT. The location of dissection was the celiac trunk in three
      and SMA in four. In all cases, the diagnosis was made by identifying an intimal
      flap on contrast-enhanced CT images. Extension of dissection to the hepatic
      artery was found in three patients. A number of associated imaging findings were
      also present: infiltration of the fat surrounding the vessel (four cases),
      aneurysmal dilatation (six), thrombosed false lumen (four), significant stenosis
      (two), and additional aortic or visceral artery aneurysm (four). One patient had
      renal infarction 2 weeks after initial presentation. Extensive evaluation of all
      patients revealed no serologic evidence to support the presence of vasculitis or
      an inflammatory disorder. All were treated conservatively with antihypertensive
      drugs, anti-inflammatory drugs, steroids, and anticoagulants. CONCLUSION:
      Isolated spontaneous splanchnic artery dissection should be considered in the
      differential diagnosis of acute abdominal pain.

PMID- 25049003
TI  - Evolving concepts in MDCT diagnosis of penetrating diaphragmatic injury.
AB  - This article reviews current and evolving concepts in the diagnosis of
      penetrating diaphragmatic injury with multidetector CT (MDCT). As criteria for
      nonoperative management in the setting of penetrating trauma become more
      inclusive, confident exclusion of penetrating diaphragmatic injury (PDI) has
      become imperative. Diagnostic performance of MDCT for PDI has improved
      substantially with the use of thin sections and multiplanar reformats. Evaluation
      of injury trajectory in nonstandard planes using 3D post-processing software can
      aid in the diagnosis. Contiguous injury and transdiaphragmatic trajectory are the
      best predictors of PDI. Careful appraisal of the diaphragm for defects should be
      undertaken in all patients with thoracoabdominal penetrating trauma. 

PMID- 25049004
TI  - SBA-15-functionalized 3-oxo-ABNO as recyclable catalyst for aerobic oxidation of
      alcohols under metal-free conditions.
AB  - The nitroxyl radical 3-oxo-9-azabicyclo [3.3.1]nonane-N-oxyl (3-oxo-ABNO) has
      been prepared using a simple protocol. This organocatalyst is found to be an
      efficient catalyst for the aerobic oxidation of a wide variety of alcohols under
      metal-free conditions. In addition, the preparation and characterization of a
      supported version of 3-oxo-ABNO on ordered mesoporous silica SBA-15 (SABNO) is
      described for the first time. The catalyst has been characterized using several
      techniques including simultaneous thermal analysis (STA), transmission electron
      microscopy (TEM), and nitrogen sorption analysis. This catalyst exhibits
      catalytic performance comparable to its homogeneous analogue and much superior
      catalytic activity in comparison with (2,2,6,6-tetramethylpiperidin-1-yl)oxy
      (TEMPO) for the aerobic oxidation of almost the same range of alcohols under
      identical reaction conditions. It is also found that SABNO can be conveniently
      recovered and reused at least 12 times without significant effect on its
      catalytic efficiency. 

PMID- 25049005
TI  - Non-compaction delineates amyotrophic lateral sclerosis from metabolic myopathy.

PMID- 25049006
TI  - Diagnosis of arrhythmogenic cardiomyopathy with day to day ECG changes:
      recognition only after electrical storm.

PMID- 25049007
TI  - Heart rate on admission independently predicts in-hospital mortality in acute
      ischemic stroke patients.
AB  - BACKGROUND: Higher heart rate (HR) is associated with worse outcomes - in
      particular death - in long term follow-up of patients with vascular diseases. We
      investigated the association between HR measured on admission and early in
      hospital mortality in acute ischemic stroke patients. METHODS: Over a period of
      30 months all patients admitted to our hospital with acute ischemic stroke but
      without atrial fibrillation were prospectively enrolled. Univariate and multiple
      logistic regression analyses were conducted to estimate the impact of HR on in
      hospital mortality. HR was analyzed as continuous and categorical variable
      (tertiles). RESULTS: A total of 1335 patients (median age 73 (IQR 65-81), median
      National Institutes of Health Stroke Scale score 4 (IQR 2-8), median length of
      stay 5 days (IQR 4-7), female sex 46%) were studied. In-hospital mortality was
      2.6%. When analyzed as categorical variable, HR >= 83 bpm was independently
      associated with in-hospital mortality after adjustment for predictors of poor
      outcome compared to the reference tertile (HR <= 69 bpm) (adjusted odds ratio
      4.42, 95% CI 1.36-14.42, p=0.01). When HR was modeled as continuous variable,
      relative risk for in-hospital death was elevated by 40% for every additional 10
      bpm (p=0.003). These results were not changed by including beta-blockers as
      covariate into the multiple regression model. CONCLUSIONS: HR on admission is
      independently associated with in-hospital mortality in acute ischemic stroke
      patients suggesting early negative effects of autonomic imbalance. HR may
      represent a therapeutic target to improve outcome after ischemic stroke.

PMID- 25049008
TI  - Minimal important difference for 6-minute walk test distances among patients with
      chronic heart failure.
AB  - BACKGROUND: The 6-minute walk test (6 WT) is an established tool in the
      assessment of endurance and prognosis in patients with chronic heart failure
      (CHF). For these patients there is very limited data on biological variation of 6
      WT distances. We determined the minimal important difference (MID) for the 6 WT
      in patients with stable systolic CHF. METHODS: Two cohorts of patients with
      stable systolic CHF were included from the outpatients' clinic of the University
      of Heidelberg. In these cohorts, two 6 WT measurements were performed - in cohort
      1 (n=461) 180 days and in cohort 2 (n=512) 365 days apart. Stability was defined
      as the absence of clinical events (3 months before the first test, between both
      tests, and 6 months after the second test) and stability of symptoms (NYHA)
      between tests. Using a standard error of measurement (SEM)-based approach, we
      determined the MID for both cohorts. RESULTS: The intraclass correlation
      coefficient was 0.89 at 180 days and 0.88 at 365 days. The results were
      consistent for groups stratified for age, gender, etiology of CHF, and individual
      NYHA class. The MID for the 6 WT in stable CHF patients was 35 m and 37 m between
      presentation and 180 and 365 days, respectively. CONCLUSION: Submaximal exercise
      capacity as represented by the 6 WT varies little in stable CHF patients for up
      to 1-year intervals. The MID for changes in 6 WT values in patients with stable
      CHF over a period of 6 to 12 months is ~ 36 m.

PMID- 25049009
TI  - Three-year clinical outcomes of staged, ad hoc and culprit-only percutaneous
      coronary intervention in patients with ST-segment elevation myocardial infarction
      and multivessel disease.

PMID- 25049010
TI  - Intracoronary mesenchymal stem cell transplantation in patients with ischemic
      cardiomyopathy.

PMID- 25049011
TI  - Coronary vessel floating sign and vasospastic angina in a patient with cardiac
      lymphoma.

PMID- 25049012
TI  - A simple pacing maneuver to overcome T-wave oversensing and ensure complete
      biventricular pacing.

PMID- 25049013
TI  - Increased concentration of circulating angiogenesis and nitric oxide inhibitors
      induces endothelial to mesenchymal transition and myocardial fibrosis in patients
      with chronic kidney disease.
AB  - BACKGROUND: Sudden cardiovascular death is increased in chronic kidney disease
      (CKD). Experimental CKD models suggest that angiogenesis and nitric oxide (NO)
      inhibitors induce myocardial fibrosis and microvascular dropout thereby
      facilitating arrhythmogenesis. We undertook this study to characterize
      associations of CKD with human myocardial pathology, NO-related circulating
      angiogenesis inhibitors, and endothelial cell behavior. METHODS: We compared
      heart (n=54) and serum (n=162) samples from individuals with and without CKD, and
      assessed effects of serum on human coronary artery endothelial cells (HCAECs) in
      vitro. Left ventricular fibrosis and capillary density were quantified in post
      mortem samples. Endothelial to mesenchymal transition (EndMT) was assessed by
      immunostaining of post-mortem samples and RNA expression in heart tissue obtained
      during cardiac surgery. Circulating asymmetric dimethylarginine (ADMA),
      endostatin (END), angiopoietin-2 (ANG), and thrombospondin-2 (TSP) were measured,
      and the effect of these factors and of subject serum on proliferation, apoptosis,
      and EndMT of HCAEC was analyzed. RESULTS: Cardiac fibrosis increased 12% and 77%
      in stage 3-4 CKD and ESRD and microvascular density decreased 12% and 16% vs.
      preserved renal function. EndMT-derived fibroblast proportion was 17% higher in
      stage 3-4 CKD and ESRD (P trend = 0.02). ADMA, ANG, TSP, and END concentrations
      increased in CKD. Both individual factors and CKD serum increased HCAEC apoptosis
      (P=0.02), decreased proliferation (P=0.03), and induced EndMT. CONCLUSIONS: CKD
      is associated with an increase in circulating angiogenesis and NO inhibitors,
      which impact proliferation and apoptosis of cardiac endothelial cells and promote
      EndMT, leading to cardiac fibrosis and capillary rarefaction. These processes may
      play key roles in CKD-associated CV disease.

PMID- 25049015
TI  - Non-invasive evaluation of coronary flow reserve with transthoracic Doppler
      echocardiography predicts the presence of significant stenosis in coronary
      arteries.

PMID- 25049014
TI  - Echocardiographic diagnosis of sinus of Valsalva aneurysm.

PMID- 25049016
TI  - Endothelial dysfunction in heart failure rats exposed to real urban air
      pollution.

PMID- 25049017
TI  - Heart failure imaging patterns in systemic lupus erythematosus. Evaluation using
      cardiovascular magnetic resonance.

PMID- 25049019
TI  - Salvage photodynamic therapy for persistent oesophageal cancer after
      chemo/radiation therapy.

PMID- 25049020
TI  - Photodynamic therapy in China: Over 25 years of unique clinical experience Part
      One-History and domestic photosensitizers.
AB  - Photodynamic therapy (PDT) was started in the People's Republic of China in the
      early 1980s after domestically produced hematoporphyrin derivative (HpD) became
      available. Since then, numerous photosensitizers have been synthesized and
      evaluated. Several promising ones have undergone clinical investigations and a
      few have entered into formal clinical trials. Various lasers and non-coherent
      light sources have been developed in China to facilitate domestic
      photosensitizers and clinical PDT applications. Chinese pioneered PDT protocols
      for treating nasopharyngeal carcinoma, liver carcinoma, port-wine stains (PWS)
      and urethral condylomata acuminata. Over the past 25 years Chinese physicians
      have treated several thousands patients, gained substantial experience in both
      basic sciences and clinical applications, and generated a great number of
      clinical reports. PDT related research and clinical activities would most likely
      continue to grow in China. The Part One of this article provides an overview on
      China's PDT history and domestic photosensitizers. Clinical PDT data of
      nasopharyngeal carcinoma, liver cancer and port-wine stains will be discussed in
      the Part Two of this article. 

PMID- 25049018
TI  - Complications in the clinical course of tako-tsubo cardiomyopathy.
AB  - OBJECTIVE: This study evaluated the frequency, severity and outcome of
      complications in the clinical course of tako-tsubo cardiomyopathy (TTC).
      BACKGROUND: TTC is regarded as a benign disease since left ventricular (LV)
      function returns to normal within a short time. However, severe complications
      have been reported in selected patients. METHODS: From 37 hospitals, 209 patients
      (189 female, age 69 +/- 12 years) were prospectively included in a TTC registry.
      RESULTS: Complications developed in 108/209 patients (52%); 23 (11%) had >2
      complications. Complications occurred median 1 day after symptom onset, and 77%
      were seen within 3 days. Arrhythmias were documented in 45/209 patients (22%)
      including atrial fibrillation in 32 (15%) and ventricular tachycardia in 17 (8%).
      Of 8 patients resuscitated (4%), 6 survived. Additional complications were right
      ventricular involvement (24%), pulmonary edema (13%), cardiogenic shock (7%),
      transient intraventricular pressure gradients (5%), LV thrombi (3%) and stroke
      (1%). During hospitalization, 5/209 patients (2.5%) died. Patients with
      complications were older (70 +/- 13 vs 67 +/- 10 years, p=0.012), had a higher
      heart rate (91 +/- 26 vs 83 +/- 19/min, p=0.025), more frequently Q? waves on the
      admission ECG (36% vs 21%, p=0.019) and a lower LV ejection fraction (47 +/- 15
      vs 54 +/- 14%, p = 0.002). Multivariate regression analysis identified Q-waves on
      admission (OR 2.49, 95% CI 1.23-5.05, p=0.021) and ejection fraction <= 30% (OR
      4.03, 95% CI 1.04-15.67, p=0.022) as independent predictors for complications.
      CONCLUSIONS: TTC may be associated with severe complications in half of the
      patients. Since the majority of complications occur up to day 3, monitoring is
      advisable for this time period.

PMID- 25049021
TI  - Salvage photodynamic therapy for persistent esophageal cancer after
      chemoradiation therapy.
AB  - BACKGROUND: Locally advanced esophageal cancer may not be completely eradicated
      after chemoradiation therapy (CRT) and further treatment options are limited.
      Since 1998, we have used porfimer sodium photodynamic therapy (PDT) for
      inoperable patients with persistent mucosal carcinoma after CRT. METHODS: Seven
      patients have undergone PDT after CRT: median age 75 (range 68-85), four patients
      male, three patients female. After upper endoscopy with biopsies documented
      neoplasm after CRT, patients were evaluated with contrast-enhanced computed
      tomography of the chest and abdomen as well as endoscopic ultrasound to confirm
      persistence/recurrence of only mucosal disease. RESULTS: Two patients had
      squamous carcinoma while five patients had Barrett's adenocarcinoma (Barrett's
      median segment length=8cm; range 5-10cm). PDT was performed after infusion of
      2mg/kg porfimer sodium using a median light dose of 150J/cm (range 100-200) using
      the bare fiber method. After PDT, all patients developed strictures requiring
      dilation (median number of dilations required=5, range 1-18). These patients have
      subsequently been followed with endoscopy every 3-6 months (mean follow up=30
      months, range 12-50 months). After an initial response, the two patients with
      squamous cell carcinoma have subsequently been found to have recurrent disease
      and are being treated with erlotinib. The other five patients treated for
      Barrett's carcinoma have remained disease free although one had died 33 months
      from metastatic colon cancer. CONCLUSION: In selected patients, PDT may be useful
      in the treatment of persistent/recurrent mucosal esophageal cancer after
      incomplete response to CRT.

PMID- 25049022
TI  - Salvage PDT for persistent esophageal cancer after chemoradiotherapy.

PMID- 25049023
TI  - Salvage photodynamic therapy A new application for esophageal cancer?

PMID- 25049024
TI  - Light dosimetry measurements during ALA-PDT of Barrett's oesophagus.
AB  - A fibre optic probe and compact light detection system has been used to monitor
      the fluence-rate at the tissue surface during 5-aminolaevulinic acid based
      photodynamic therapy (PDT) of Barrett's oesophagous. The contributions from three
      specific wavelengths were recorded, corresponding to the combination of
      therapeutic laser light and fluorescence emission from protoporphyrin IX (635nm),
      the fluorescence from an oxidation product of the photosensitiser (670nm), and
      the protoporphyrin IX fluorescence alone (705nm). We have found that light
      scattering results in an enhancement of the therapeutic fluence-rate, and hence
      light dose, by approximately 70%. At the onset of therapy the fluorescence
      provides a 10% contribution to the overall fluence-rate at 635nm. The dynamics of
      photosensitiser bleaching could be extracted from the depletion in light signals.
      By defining a bleaching dose as the 635nm light fluence delivered over the period
      during which the photosensitiser fluorescence decays to 1/e(3) of its initial
      value, we find that the average ratio of bleaching to total dose is 33%. Further,
      the fluorescence contributes approximately 5% of the bleaching light dose. These
      results suggest that the prescribed period of therapeutic light exposure may be
      reduced with no loss in clinical efficacy, but with a consequent improvement in
      patient tolerance to this therapy. 

PMID- 25049026
TI  - The influence of storage conditions on delta amino levulinic acid induced
      toxicity and phototoxicity in vitro.
AB  - Delta amino levulinic acid photodynamic therapy (ALA-PDT) represents one of the
      most prominent advances in PDT. ALA itself or its derivatives are marketed for a
      variety of clinical indications. Despite the development of clinical
      applications, experimental ALA results are very heterogeneous and experimentally
      used parameters are still not standardized. This suggests that some problems
      remain unsolved that are likely to impair experiments to be performed but also
      that clinical results obtained could be greatly improved. Frequently unmentioned
      or imprecise data concern solvents, pH of ALA solutions, storage time, ALA
      degradation or ALA efficacy. In addition, diversity of experimental model is huge
      while capabilities of ALA transformation into PpIX are known to vary from one
      cell to the other. Thus, the aim of the present paper was to quantify the level
      of ALA degradation or changes in ALA efficacy using one single cell line without
      presuming of the mechanisms and determine the conditions of storage inducing the
      best transformation into PpIX and/or cell phototoxicity. We added ALA diluted in
      water, PBS or RPMI to C6 cells, a murine brain tumour cell line that can be used
      in vivo as an orthotopic graft. We measured in cells used as tools for final bio
      efficacy estimation, both the induced fluorescence and phototoxicity in various
      conditions of storage before use chosen to be as close as possible to the real
      lab conditions. Water had been found to better preserve ALA than, respectively,
      PBS and RPMI and this for any temperature or storage durations. The lowest
      temperature and the shortest duration for storage used had also been shown to
      better preserve ALA-induced fluorescence and phototoxicity. The fact that these
      properties were found to be better preserved in 7.4 buffered solvent could be in
      relationship with a fast ALA condensation occurring at neutral or lightly acidic
      pH modifying its availability for an optimal transformation into PpIX. 

PMID- 25049025
TI  - The effect of dimethylsulfoxide, 1-[2-(decylthio)ethyl]azacyclopentan-2-one and
      Labrafac((r))CC on porphyrin formation in normal mouse skin during topical
      application of methyl 5-aminolevulinate: A fluorescence and extraction study.
AB  - In this work, the effect of 10% of dimethylsulfoxide (DMSO), 1-[2
      (decylthio)ethyl]azacyclopentan-2-one (HPE-101) and Labrafac((r))CC (a mixture of
      caprylic and capric acid triglycerides) on porphyrin formation in mouse skin
      during topical application of methyl 5-aminolevulinate (MAL) was studied. The
      porphyrin level in mouse skin was determined by measuring directly fluorescence
      and by extraction method. The porphyrin fluorescence kinetics during continuous
      application of MAL in creams in concentrations 2, 10 and 20% (wt./wt.) for up to
      7h showed that in this concentration range the kinetics of porphyrin production
      in the site of application does not depend significantly on the MAL
      concentration. After 24h of application of all studied creams the porphyrin
      fluorescence in the area of treatment was dramatically reduced to be about two
      fold higher than the skin autofluorescence, suggesting a significant decrease of
      the porphyrin concentration in these sites, although in all cases traces of
      porphyrins were found. It was found by extraction method that a 10% MAL cream
      with 10% DMSO for 4h increased the concentration of porphyrin about four-fold
      compared with 10% MAL cream alone. The presence of 10% HPE-101 or 10%
      Labrafac((r))CC in the 10% MAL cream increased the porphyrin concentration in the
      area of application about 2.5- and 2-fold, respectively, as compared with MAL
      cream without enhancers. No statistically significant difference was found
      between the effects of the creams containing 10% MAL with 10% HPE-101 or 10%
      Labrafac((r))CC. The results obtained after 24h of mouse skin treatment with the
      same creams showed a large decrease of porphyrin formation in comparison with
      results found after 4h. All porphyrin concentrations measured after this time of
      MAL creams application were similar. Skin erythema was observed using MAL cream
      with DMSO and HPE-101, but not with Labrafac((r))CC. Our work suggests that the
      new penetration enhancer Labrafac((r))CC in creams with MAL may be used to
      increase the penetration of MAL through the mouse skin and at the same time
      increase production of porphyrin in the skin. This may reduce skin erythema,
      which is induced by DMSO and HPE-101. 

PMID- 25049027
TI  - Performance of a contact textile-based light diffuser for photodynamic therapy.
AB  - BACKGROUND: Medical textiles offer a unique contact opportunity that could
      provide value-added comfort, reliability, and safety for light or laser-based
      applications. We investigated a luminous textile diffuser for use in photodynamic
      therapy. METHODS: Textile diffusers are produced by an embroidery process.
      Plastic optical fibers are bent and sewn into textile to release light by
      macrobending. A reflective backing is incorporated to improve surface
      homogeneity, intensity, and safety. Clonogenic assay (MCF-7 cells) and trypan
      blue exclusion (NuTu19 cells) tests were performed in vitro using 0.1MUg/ml m
      THPC with three textile diffusers and a standard front lens diffuser. Heating
      effects were studied in solution and on human skin. PDT application in vivo was
      performed with the textile diffuser on equine sarcoids (three animals,
      50mW/cm(2), 10-20J) and eight research animals. Lastly, computer simulations were
      performed to see how the textile diffuser might work on a curved object. RESULTS:
      At low fluency rate, there is a trend for the textile diffuser to have lower
      survival rates than the front lens diffuser for both cell lines. The textile
      diffuser was observed to retain more heat over a long period (>1min). All animals
      tolerated the treatments well and showed similar initial reactions. The
      simulations showed a likely focusing effect in a curved geometry. CONCLUSIONS:
      The initial feasibility and application using a textile-based optical diffuser
      has been demonstrated. Possibilities that provide additional practical advantages
      of the textile diffuser are discussed.

PMID- 25049028
TI  - Different pain sensations in photodynamic therapy of nodular basal cell carcinoma
      Results from a prospective trial and a review of the literature.
AB  - BACKGROUND: Pain is a major side effect of topical photodynamic therapy (PDT), a
      relatively new and non-invasive treatment for particular types of basal cell
      carcinoma (BCC). In this study, we sought to characterise in more detail the
      quality and intensity of pain associated with PDT. Furthermore, we studied if
      gender, tumour size and localization as well as different light sources with
      comparable wavelengths had an influence on the pain. METHODS: A total of 64
      nodular BCCs in 55 patients, of which 48 BCCs underwent preceding debulking, were
      treated with 5-aminolevulinic acid (ALA-PDT). Two metal halogen light sources
      were randomly used. Pain assessment was performed using a visual analogue scale
      (VAS). RESULTS: All patients experienced pain during illumination and 41.8% after
      illumination. The mean pain intensity was 3.88 with most patients experiencing
      burning (82.5%) or stinging (36.8%) sensations. Illumination with the
      Medeikonos((r)) light source was experienced less painful than the Waldmann((r))
      lamp (4.64 versus 3.40; p=0.027). Gender as well as tumour localization and size
      did not alter the pain scores. Likewise, no differences were observed between
      patients who underwent debulking and those who did not. CONCLUSIONS: Treatment of
      single BCCs with ALA-PDT rarely results in unbearable pain. However, the degree
      of pain can vary depending on the light source used. Further studies are needed
      to unravel the pathomechanisms underlying the development of pain in PDT in order
      to develop adequate solutions for this undesirable side effect.

PMID- 25049029
TI  - Laser florence 2005 conference report.

PMID- 25049030
TI  - Negative mood regulation expectancies moderate the relationship between
      psychological abuse and avoidant coping.
AB  - This study explored the relationships among psychological abuse, attitudes about
      intimate partner violence (IPV), negative mood regulation expectancies (NMRE),
      and coping. Participants were 126 female college students in dating,
      cohabitating, or married relationships within the previous year. In one single
      session, they completed self-report scales measuring IPV, NMRE, and coping.
      Results indicated that women reporting higher levels of psychological abuse
      reported less negative attitudes toward IPV, engaged in less-active coping
      responses, and had lower NMRE. Psychological abuse was a significant predictor of
      avoidant coping, while NMRE significantly predicted both active and avoidant
      coping. In addition, the interaction of NMRE * Psychological abuse added
      incremental prediction of avoidant coping. Implications for research and practice
      are discussed. 

PMID- 25049031
TI  - Factors associated with intimate partner violence against married women in Nepal.
AB  - This study was to explore the factors associated with intimate partner violence
      (IPV) in Nepal. A sample of 3,373 married women was taken from the 2011 Nepal
      Demographic and Health Survey. Multilevel logistic regression methods were used
      to analyze the data. The results show that 28.31% of the population experienced
      the IPV in the past year. The results indicate that female illiteracy, low
      economic status, violent family history, and a lack of decision-making autonomy
      were associated with IPV. Regarding family background, whether or not the husband
      was an alcoholic, the husband's level of education, and a higher number of
      children were risk factors associated with IPV. At the community level, women
      most at risk of IPV were those living in the Terai region, and women belonging to
      underprivileged castes and ethnic groups. The findings suggest the need for
      context-specific policy formation and the need for the creation of the certain
      intervention programs designed to mitigate IPV in Nepal. 

PMID- 25049032
TI  - Sexual history disclosure polygraph outcomes: do juvenile and adult sex offenders
      differ?
AB  - Despite the empirical and theoretical chasm between the opponents and proponents
      of polygraphy, its use is prominent among sex offender agencies in the United
      States. However, current research on polygraph examination outcomes among
      juvenile sex offenders, along with potential differences from their adult
      counterparts, is scarce and outdated. In the present study, we assess the
      difference between juvenile and adult sex offenders in terms of the propensity
      for passing a sexual history disclosure polygraph examination. A sample of 324
      sex offenders (86 juveniles and 238 adults) who engaged in a sexual history
      disclosure polygraph examination as part of their treatment in an Intermountain
      West sex offender treatment agency was used for the analysis. Results from
      preliminary and logistic regression analyses indicate that juvenile and adult
      offenders do not significantly differ in the likelihood of passing a sexual
      history disclosure polygraph examination. Implications and limitations are
      discussed. 

PMID- 25049033
TI  - Looking beyond the illness: forensic service users' perceptions of
      rehabilitation.
AB  - The aim of this qualitative study was to explore perspectives on rehabilitation
      of those detained in a New Zealand forensic hospital setting. Twenty forensic
      service users participated in individual interviews, which were audio-taped,
      transcribed verbatim, and subjected to thematic analysis. The analysis identified
      seven themes that were broadly categorized into those that concerned the
      rehabilitation context (external) and those that more directly reflected the
      forensic service user's personal experience (internal). External themes
      highlighted a person-centered approach, the nature of relationships with staff,
      consistency of care, and awareness of the rehabilitation pathway. Internal themes
      related to forensic service users' self-evaluations, agency, and coping
      strategies. These findings are discussed within the broader context in which
      rehabilitation took place. 

PMID- 25049034
TI  - College students' perceived risk of sexual victimization and the role of
      optimistic bias.
AB  - Many college women believe that their chances of experiencing a sexual assault
      are less than their peers. This phenomenon, called optimistic bias, has been
      hypothesized to be one important element to address in sexual assault risk
      reduction and awareness programs aimed at reducing women's chances of
      experiencing a sexual assault. The present study examined the role that
      participants' (N = 89) perceived similarity to a narrator (portraying a sexual
      assault survivor) describing an assault plays in reducing this bias. The age of
      the narrator was manipulated (similar or dissimilar to age of participants) with
      the aim of assessing whether the program could produce reductions in optimistic
      bias for those participants who watched a video of someone similar to them in
      age. A significant interaction between pre- and post-program and age similarity
      indicated a significant decrease in optimistic bias from pre- to posttest for the
      similar group. Furthermore, an exploratory analysis indicated optimistic bias for
      White participants decreased from pre- to posttest, whereas optimistic bias for
      the Black participants increased. These results suggest that some factors such as
      age similarity may reduce optimistic bias in sexual assault risk reduction and
      awareness programs. However, a race dissimilarity may increase optimistic bias.
      Thus, more research is needed to understand the factors that affect optimistic
      bias with regard to sexual assault awareness. 

PMID- 25049036
TI  - In vitro antifungal susceptibility of Scopulariopsis brevicaulis isolates.
AB  - In humans, Scopulariopsis is mainly associated with onychomycoses, rarely with
      cutaneous infections or with invasive mycoses. However, during the last two
      decades, deep infections caused by members of this genus have been increasing.
      Scopulariopsis brevicaulis is the most common species described as an etiologic
      agent of human disease. Previous antifungal susceptibility studies indicate that
      this species is resistant in vitro to the broad-spectrum antifungal agents that
      are available today. Here, we describe the antifungal activity of amphotericin B,
      terbinafine, ciclopirox, itraconazole, ketoconazole, and voriconazole against 40
      S. brevicaulis isolates. Antifungal susceptibility tests were performed using a
      modified Clinical and Laboratory Standards Institute M38-A2 procedure. The
      results showed that itraconazole had the highest minimal inhibitory concentration
      (MIC) of >16 mg/l; amphotericin B, voriconazole, and ketoconazole MICs were
      ranging from 4 to >16 mg/l, 8 to >16 mg/l, and 8 to >16 mg/l, respectively; and
      the best activity was found with terbinafine and ciclopirox with MICs ranging
      from 0.5 to 16 mg/l and 1 to 8 mg/l, respectively. 

PMID- 25049035
TI  - Endogenous calcium buffering at photoreceptor synaptic terminals in salamander
      retina.
AB  - Calcium operates by several mechanisms to regulate glutamate release at rod and
      cone synaptic terminals. In addition to serving as the exocytotic trigger, Ca2+
      accelerates replenishment of vesicles in cones and triggers Ca2+-induced Ca2+
      release (CICR) in rods. Ca2+ thereby amplifies sustained exocytosis, enabling
      photoreceptor synapses to encode constant and changing light. A complete picture
      of the role of Ca2+ in regulating synaptic transmission requires an understanding
      of the endogenous Ca2+ handling mechanisms at the synapse. We therefore used the
      "added buffer" approach to measure the endogenous Ca2+ binding ratio (kappaendo )
      and extrusion rate constant (gamma) in synaptic terminals of photoreceptors in
      retinal slices from tiger salamander. We found that kappaendo was similar in both
      cell types-~25 and 50 in rods and cones, respectively. Using measurements of the
      decay time constants of Ca2+ transients, we found that gamma was also similar,
      with values of ~100 s(-1) and 160 s(-1) in rods and cones, respectively. The
      measurements of kappaendo differ considerably from measurements in retinal
      bipolar cells, another ribbon-bearing class of retinal neurons, but are
      comparable to similar measurements at other conventional synapses. The values of
      gamma are slower than at other synapses, suggesting that Ca2+ ions linger longer
      in photoreceptor terminals, supporting sustained exocytosis, CICR, and Ca2+ 
      dependent ribbon replenishment. The mechanisms of endogenous Ca2+ handling in
      photoreceptors are thus well-suited for supporting tonic neurotransmission.
      Similarities between rod and cone Ca2+ handling suggest that neither buffering
      nor extrusion underlie differences in synaptic transmission kinetics.

PMID- 25049037
TI  - Relapsed and secondary disease drive the risk profile for invasive aspergillosis
      prior to stem cell transplantation in patients with acute myeloid leukemia or
      myelodysplastic syndrome.
AB  - Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) are
      at risk for invasive aspergillosis (IA) even prior to the introduction of stem
      cell transplantation (SCT). In times of increasing triazole resistance and
      changing use of antifungal prophylaxis, insight into the risk factors for IA is
      needed to improve strategies for preventing IA in this population. Consecutive
      patients who received remission-induction therapy for AML or MDS at the Leiden
      Academic Medical Centre were included. Instead of standard antifungal
      prophylaxis, an assertive protocol for diagnosis of suspected fungal infection
      was in place. IA was classified according to the revised European Organization
      for Research and Treatment of Cancer criteria. Potential predisposing
      characteristics for IA were compared by uni- and multivariate analyses. In 45
      (25%) of 184 included episodes (167 patients), IA was diagnosed prior to SCT. A
      multivariate Cox regression model demonstrated that relapsed AML (hazard ratio
      [HR] 2.4; 95% confidence interval [CI], 1.1-5.1; P = 0.02), secondary AML (HR,
      5.2; 95% CI, 2.3-11.8; P < 0.001), and prolonged duration of neutropenia (HR,
      2.2; 95% CI, 1.2-4.0; P = 0.01) were independently associated with IA. Use of
      granulocyte-colony-stimulating factor showed a trend toward a protective effect
      (HR, 0.37; 95% CI, 0.1-31.0; P = 0.06). Relapsed AML, secondary AML, and duration
      of neutropenia were independent factors for determining the risk for development
      of IA prior to SCT. The results provide further guidance for antifungal
      stewardship programs when integrating individual patient tailored decision making
      in antifungal prophylaxis strategies. 

PMID- 25049038
TI  - In vitro photodynamic inactivation of Sporothrix schenckii complex species.
AB  - Photodynamic therapy has been applied successfully against cutaneous and
      subcutaneous mycoses. We applied methylene blue as a photosensitizing agent and
      light emitting diode (InGaAlP) against Sporothrix schenckii complex species in an
      in vitro assay. The viability of the conidia was determined by counting colony
      forming units. Methylene blue in conjunction with laser irradiation was able to
      inhibit the growth of all tested samples. The in vitro inhibition of Sporothrix
      spp. isolates by laser light deserves in vivo experimental and clinical studies
      since it may be a promising treatment for cutaneous and subcutaneous
      sporotrichosis. 

PMID- 25049039
TI  - Effective method for the heat inactivation of Blastomyces dermatitidis.
AB  - Manipulation of Blastomyces dermatitidis requires the use of containment level 3
      (CL3) practices. However, access to CL3 laboratories is limited and working
      conditions are restrictive. We describe the validation of a "heat-killing" method
      to inactivate B. dermatitidis, thus allowing cellular material to be removed from
      the CL3 laboratory for subsequent DNA isolation that is suitable for genetic
      applications. 

PMID- 25049042
TI  - Impurity cyclotron resonance of anomalous Dirac electrons in graphene.
AB  - We have investigated a new feature of impurity cyclotron resonances common to
      various localized potentials of graphene. A localized potential can interact with
      a magnetic field in an unexpected way in graphene. It can lead to formation of
      anomalous boundstates that have a sharp peak with a width R in the probability
      density inside the potential and a broad peak of size magnetic length l outside
      the potential. We investigate optical matrix elements of anomalous states and
      find that they are unusually small and depend sensitively on the magnetic field.
      The effect of many-body interactions on their optical conductivity is
      investigated using a self-consistent time-dependent Hartree-Fock approach. For a
      completely filled Landau level we find that an excited electron-hole pair,
      originating from the optical transition between two anomalous impurity states, is
      nearly uncorrelated with other electron-hole pairs, although it displays
      substantial exchange self-energy effects. This absence of correlation is a
      consequence of a small vertex correction in comparison to the difference between
      renormalized transition energies computed within the one electron-hole pair
      approximation. However, an excited electron-hole pair originating from the
      optical transition between a normal and an anomalous impurity state can be
      substantially correlated with other electron-hole states with a significant
      optical strength.

PMID- 25049040
TI  - G protein-coupled receptor kinase 5 gene polymorphisms are associated with
      postoperative atrial fibrillation after coronary artery bypass grafting in
      patients receiving beta-blockers.
AB  - BACKGROUND: We hypothesized that genetic variations in the adrenergic signaling
      pathway and cytochrome P450 2D6 enzyme are associated with new-onset atrial
      fibrillation (AF) in patients who underwent coronary artery bypass grafting and
      were treated with perioperative beta-blockers (BBs). METHODS AND RESULTS: Two
      cohorts of patients who underwent coronary artery bypass grafting and received
      perioperative BBs at Duke University Medical Center were studied. In a discovery
      cohort of 563 individuals from the Perioperative Genetics and Safety Outcomes
      Study (PEGASUS), using a covariate-adjusted logistic regression analysis, we
      tested 492 single-nucleotide polymorphisms (SNPs) in 10 candidate genes of the
      adrenergic signaling pathway and cytochrome P450 2D6 for association with
      postoperative AF despite perioperative BB therapy. SNPs meeting a false discovery
      rate <=0.20 (P<0.002) were then tested in the replication cohort of 245
      individuals from the Catheterization Genetics biorepository. Of the 492 SNPs
      examined, 4 intronic SNPs of the G protein-coupled kinase 5 (GRK5) gene were
      significantly associated with postoperative AF despite perioperative BB therapy
      in the discovery cohort with additive odds ratios between 1.72 and 2.75
      (P=4.78*10(-5) to 0.0015). Three of these SNPs met nominal significance levels in
      the replication cohort with odds ratios between 2.07 and 2.60 (P=0.007 to 0.016).
      However, meta-analysis of the 2 data sets cohorts suggested strong association
      with postoperative AF despite perioperative BB therapy in all 4 SNPs (meta-P
      values from 1.66*10(-6) to 3.39*10(-5)). CONCLUSIONS: In patients undergoing
      coronary artery bypass grafting, genetic variation in GRK5 is associated with
      postoperative AF despite perioperative BB therapy.

PMID- 25049041
TI  - Toll-like receptor 4 regulates platelet function and contributes to coagulation
      abnormality and organ injury in hemorrhagic shock and resuscitation.
AB  - BACKGROUND: Growing evidence indicates that the presence of toll-like receptor 4
      (TLR4) on platelets is a key regulator of platelet number and function. Platelets
      exposed to TLR4 agonists may serve to activate other cells such as neutrophils
      and endothelial cells in sepsis and other inflammatory conditions. The functional
      significance of platelet TLR4 in hemorrhagic shock (HS), however, remains
      unexplored. METHODS AND RESULTS: Using thromboelastography and platelet
      aggregometry, we demonstrate that platelet function is impaired in a mouse model
      of HS with resuscitation. Further analysis using cellular-specific TLR4 deletion
      in mice revealed that platelet TLR4 is essential for platelet activation and
      function in HS with resuscitation and that platelet TLR4 regulates the
      development of coagulopathy after hemorrhage and resuscitation. Transfusion of
      TLR4-negative platelets into mice resulted in protection from coagulopathy and
      restored platelet function. Additionally, platelet-specific TLR4 knockout mice
      were protected from lung and liver injury and exhibited a marked reduction in
      systemic inflammation as measured by circulating interleukin-6 after HS with
      resuscitation. CONCLUSIONS: We demonstrate for the first time that platelet TLR4
      is an essential mediator of the inflammatory response as well as platelet
      activation and function in HS and resuscitation.

PMID- 25049043
TI  - Association between abuse history and adolescent pregnancy: a meta-analysis.
AB  - PURPOSE: Although a purported risk factor for early pregnancy is abuse history,
      the strength of this association has been inconsistent across studies and may
      vary as a function of abuse type. The purpose of this meta-analysis was to
      examine the extent to which sexual, physical, and emotional abuse, as well as
      neglect, increased the risk of adolescent pregnancy. METHODS: A search of studies
      through MEDLINE, EMBASE, PsycINFO, Social Work Abstracts, and Web of Science was
      conducted. Studies were retained if they included (1) women who became pregnant
      before 20 years of age; (2) a comparison group of nonpregnant adolescents; and
      (3) abuse experience (<18 years of age). RESULTS: Thirty-eight independent
      samples provided 70 estimates of effect sizes, derived from 75,390 participants.
      Both sexual and physical abuse were associated with an increased risk of
      adolescent pregnancy (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.75
      2.38 and OR, 1.48; CI, 1.24-1.76, respectively). The strongest effect was for the
      co-occurrence of sexual and physical abuse (OR, 3.83; CI, 2.96-4.97]).
      Nonsignificant effect sizes were found for emotional abuse (OR, 1.01; CI, .70
      1.47) and neglect (OR, 1.29; CI, .77-2.17]), although these were moderated by
      journal impact factor, that is, greater effect sizes were reported in higher
      impact journals. CONCLUSIONS: The results of this meta-analysis reveal that the
      strength of the association between abuse and adolescent pregnancy varies as a
      function of abuse subtype. Sexual and physical abuse were associated with
      increased risk for adolescent pregnancy, whereas emotional abuse and neglect were
      not.

PMID- 25049044
TI  - Measuring pediatric resident competencies in adolescent medicine.
AB  - PURPOSE: To compare third-year pediatric resident competence on an adolescent
      medicine with competence in treating younger children. METHODS: The participants
      were third-year residents (2010 [n = 24] and 2011 [n = 23]) at University of
      Colorado School of Medicine. Resident competence was measured in the domains of
      professionalism, communication, and history-taking skills in a multicase
      Objective Structured Clinical Examination. RESULTS: Percent correct scores in
      professionalism, history-taking, and communication skills on the adolescent case
      ranked in the bottom half of cases in both years. T-tests comparing mean score
      difference between the adolescent case and pediatric cases combined were
      statistically significant for professionalism (79.57 +/- 4.15 vs. 89.51 +/-
      14.14, p = .01) and history taking (66.27 +/- 11.02 vs. 75.10 +/- 18.40, p =
      .05). CONCLUSIONS: Resident's history taking addressed immediate issues but not
      public health issues with adolescents. The professionalism findings suggest that
      residents engage in less patient-centered care when caring for adolescents, even
      while their communication skills remain on par.

PMID- 25049045
TI  - Meaning of relative gene expression in multilayered cultures of epidermal
      keratinocytes.
AB  - Reconstructed human epidermis (RHE) has become an in vitro model of choice for
      studying cell and tissue functions. Analysis of gene expression over the course
      of reconstruction must take into account the heterogeneous differentiation states
      of keratinocytes reconstituting the typical epidermal layers. In monolayer
      cultures, relative mRNA expression levels of differentiation markers are usually
      expressed as a ratio versus a classical reference gene (also named house-keeping
      gene) tested to be expressed equally in certain experimental conditions. Applied
      to complex tissues in which the cell number increases over time together with
      differentiation, calculation of relative gene expression does not take enough
      into account a crucial phenomenon: epidermal morphogenesis results in progressive
      restriction of differentiation markers, such as involucrin, to a specific layer,
      or in the delayed onset of mRNA expression of filaggrin or TMEM45A for instance
      following stratification. Our study illustrates that comparing the relative
      expression level of mRNAs to that of a basal layer-specific gene (e.g. ITGA6)
      better illustrates the contribution of specific differentiation markers to the
      process of epidermal morphogenesis. 

PMID- 25049046
TI  - Canakinumab for the treatment of children with colchicine-resistant familial
      Mediterranean fever: a 6-month open-label, single-arm pilot study.

PMID- 25049047
TI  - What does "brief" mean? A theoretical critique of the concept of brief therapy
      from a psychoanalytic viewpoint.
AB  - The concept of "brief therapy" contains internal contradictions. The techniques
      suggested by brief therapists are the same techniques that have been discussed
      historically in debates on theory of technique, both within and without
      psychoanalysis (e.g., the experiential factor at the center of the Freud-Ferenczi
      confrontation is also an important aspect of Gestalt therapy). A time limit is
      the only operational criterion that allows a rigorous definition of brief
      therapy; without this criterion it is impossible to discriminate between "brief"
      and simply "good" therapies (i.e., those in which patients are successfully
      treated in a short time). An important question is why, with a given patient, a
      therapist should decide, a priori, to terminate a treatment within a set time.
      Two clinical examples are presented, illustrating the usefulness of Eissler's
      concept of parameters as a heuristic framework to identify the potentially
      defensive nature of both "brief" and "long-term" therapy. 

PMID- 25049049
TI  - Single-sided renal denervation may be not suitable for patients with significant
      renal artery stenosis.

PMID- 25049048
TI  - Dietary medium chain fatty acid supplementation leads to reduced VLDL lipolysis
      and uptake rates in comparison to linoleic acid supplementation.
AB  - Dietary medium chain fatty acids (MCFA) and linoleic acid follow different
      metabolic routes, and linoleic acid activates PPAR receptors. Both these
      mechanisms may modify lipoprotein and fatty acid metabolism after dietary
      intervention. Our objective was to investigate how dietary MCFA and linoleic acid
      supplementation and body fat distribution affect the fasting lipoprotein subclass
      profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a
      randomized double blind cross-over trial, 12 male subjects (age 51+/-7 years; BMI
      28.5+/-0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They
      were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid
      for three weeks, with a wash-out period of six weeks in between. Lipoprotein
      subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were
      studied using a combination of several stable isotope tracers. Lipoprotein and
      tracer data were analyzed using computational modeling. Lipoprotein subclass
      concentrations in the VLDL and LDL range were significantly higher after MCFA
      than after linoleic acid intervention. In addition, LDL subclass concentrations
      were higher in lower body obese individuals. Differences in VLDL metabolism were
      found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were
      elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation
      led to a less favorable lipoprotein profile than linoleic acid supplementation.
      These differences were not due to elevated VLDL production, but rather to lower
      lipolysis and uptake rates. 

PMID- 25049050
TI  - Ultrasound guided percutaneous thrombin injection in a radial artery
      pseudoaneurysm following percutaneous coronary intervention.

PMID- 25049051
TI  - Dermacentor everestianus Hirst, 1926 (Acari: Ixodidae): phylogenetic status
      inferred from molecular characteristics.
AB  - Dermacentor everestianus Hirst, 1926, is only reported in Northwestern China and
      Nepal. Few researches about this species have been involved, especially for
      molecular characteristics. The taxonomy studies of D.everestianus are mainly
      based on morphological features, and its taxonomic status is an ongoing
      controversy. To clarify the molecular characteristics and phylogenetic status of
      D.everestianus and other related species, the sequences of mitochondrial 16S
      ribosomal DNA (rDNA) and cox1 fragments were analyzed in the present study.
      Analysis of 16S rDNA and cox1 sequences showed 99.3-100% identity within
      D.everestianus individuals, with the genetic divergence among them was 0-0.0086.
      The interspecific distance of 16S rDNA and cox1 between D.everestianus and some
      other Palaearctic species including D. silvarum, D. nuttalli, and D. marginatus
      was much smaller than that between D.everestianus and Nearctic Dermacentor ticks
      (D.albipictus, D.nitens, and D.variabilis). Such relationships of these ticks
      were also verified in the phylogenetic analysis. Two major clades were recovered
      within Dermacentor spp. with more than 90% bootstrap support in the phylogenetic
      trees. D.everestianus together with D.silvarum, D.nuttalli, and D.marginatus were
      included in the clade I (Eurasia lineage). Other analyzed tick species including
      D.variabilis, D.nitens, and D.albipictus formed clade II, which are distributed
      in Nearctic realm. These indicated that the genus Dermacentor was at least
      composed of two lineages. Thus, further researches including additionally
      molecular markers on all Dermacentor species globally should be taken to
      precisely resolve relationships within Dermacentor.

PMID- 25049052
TI  - Behavioral and electrophysiological responses of Aedes albopictus to certain
      acids and alcohols present in human skin emanations.
AB  - Human skin emanations attract hungry female mosquitoes toward their host for
      blood feeding. In this study, we report the flight orientation and
      electroantennogram response of Aedes albopictus females to certain unsaturated
      acids and alcohols found in human skin. In the Y-tube olfactometer, odors of
      lactic acid and 2-methyl-3-pentanol attracted 54-65% of Ae. albopictus females at
      all doses in a dose-dependent manner. However, at the highest dose (10(-2) g),
      the acids repelled 40-45% females. Attractancy (ca. 62-68%) at lower doses and
      repellency (ca. 30-45%) at higher doses were recorded for 3-methyl-3-pentanol and
      1-octen-3-ol, while 5-hexen-1-ol, cis-2-hexen-1-ol, and trans 2-hexen-1-ol odor
      repelled ca. 55-65% of Ae. albopictus females at all doses. Antenna of female Ae.
      albopictus exhibited a dose-dependent EAG response up to 10(-3) g of L-lactic
      acid, trans-2-methyl-2-pentenoic acid, 2-octenoic acid, trans-2-hexen-1-ol and 1
      octen-3-ol stimulations; however, the highest dose (10(-2) g) caused a little
      decline in the EAG response. EAG response of 9-10-fold was elicited by lactic
      acid, 2-octenoic acid, trans-2-hexenoic acid, and 3-methyl-3-pentanol, while cis
      2-hexen-1-ol and trans-2-methyl pentenoic acid elicited 1-5-fold responses
      compared to solvent control. A blend of attractive compounds could be utilized in
      odor-baited trap for surveillance and repellent molecules with suitable
      formulation could be used to reduce the biting menace of mosquitoes.

PMID- 25049053
TI  - Grain-size distribution and heavy metal contamination of road dusts in urban
      parks and squares in Changchun, China.
AB  - Due to rapid urbanization and the scarcity of land, most of the urban parks and
      squares in cities are built close to major roads or industrial areas, where they
      are subject to many potential pollution sources, including vehicle exhaust and
      industrial emissions. The aims of this study were to determine the concentrations
      of selected metals (Pb, Cr, Cu, Ni, Zn, and Cd) in road dusts collected in urban
      parks and squares in Changchun, China, on June 1, 2013 (International Children's
      Day) and to estimate the pollution sources. The mean Pb, Cr, Cu, Ni, Zn, and Cd
      contents (70.89, 60.30, 43.56, 23.16, 170.80, and 0.3111 mg kg(-1) dry weight,
      respectively) in urban dusts were higher than their corresponding natural
      background values, particularly Pb, Cu, Zn, and Cd, which had about 2.5, 1.4,
      1.9, and 2.6-fold higher levels, respectively. The results of principal component
      analysis indicated that Cr and Ni concentrations were mainly of natural origin,
      while Pb, Cu and Zn were derived from anthropogenic activities, and Cd tended to
      be from both sources. The geoaccumulation index (I geo) of these metals in the
      urban dusts under study indicates that they are uncontaminated with Cr and Ni;
      uncontaminated to moderately contaminated with Cu and Zn; and moderately
      contaminated with Pb and Cd. In addition, five particle sizes were analyzed
      separately for heavy metal concentrations. In all studied areas, there are large
      differences in the metal-loading percentage of different particle-size fractions
      among the samples, and the particles in 250-2,000-MUm fraction are dominant in
      the total metal loading.

PMID- 25049054
TI  - Computed tomography correlates with improvement with ivacaftor in cystic fibrosis
      patients with G551D mutation.
AB  - BACKGROUND: Ivacaftor corrects the cystic fibrosis transmembrane conductance
      regulator (CFTR) gating defect associated with G551D mutation and is quickly
      becoming an important treatment in patients with cystic fibrosis (CF) due to this
      genetic mutation. METHODS: A single-center study was performed in CF patients
      receiving ivacaftor to evaluate the usefulness of high resolution computed
      tomography (HRCT) of the chest as a way to gauge response to ivacaftor therapy.
      RESULTS: Ten patients with CF were enrolled for at least one year before and
      after starting ivacaftor. At time of enrollment, mean age was 20.9 +/- 10.8
      (range 10-44) years. There were significant improvements from baseline to 6
      months in mean %FVC (93 +/- 16 to 99 +/- 16) and %FEV1 (79 +/- 26 to 87 +/- 28)
      but reverted to baseline at one year. Mean sweat chloride levels decreased
      significantly from baseline to one year. Mean weight and BMI improved at 6
      months. Weight continued to improve with stabilization of BMI at one year. Chest
      HRCT showed significant improvement at one year in mean modified Brody scores for
      bronchiectasis, mucous plugging, airway wall thickness, and total Brody scores.
      Elevated bronchiectasis and airway wall thickness scores correlated significantly
      with lower %FEV1, while higher airway wall thickness and mucus plugging scores
      correlated with more pulmonary exacerbations requiring IV and oral antibiotics
      respectively. CONCLUSIONS: Based on our findings, HRCT imaging is a useful tool
      in monitoring response to ivacaftor therapy that corrects the gating defect
      associated with the G551D-CFTR mutation.

PMID- 25049055
TI  - Navigated transcranial magnetic stimulation in amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a set of disorders
      associated with preferential degeneration of both upper and lower motor neurons.
      Navigated transcranial magnetic stimulation (nTMS) is a tool used to perform
      noninvasive functional brain mapping. We aimed to assess function of upper motor
      neurons in ALS. METHODS: nTMS was performed on 30 patients with ALS (mean age
      54.4 +/- 12.1 years) and 24 healthy volunteers (mean age 32.7 +/- 13.3 years).
      RESULTS: The resting motor threshold (MT) was significantly higher in ALS
      patients compared with controls (P < 0.001). The mean map areas were smaller in
      patients with ALS than in healthy individuals, although some patients with short
      disease duration had extended maps. CONCLUSIONS: Motor area maps serve as markers
      of upper motor neuron damage in ALS. Further research may elucidate the
      pathogenic mechanisms of the neurodegenerative process and aid in development of
      diagnostic and prognostic markers.

PMID- 25049056
TI  - Characterizing the inflammatory tissue response to acute myocardial infarction by
      clinical multimodality noninvasive imaging.
AB  - BACKGROUND: Myocardial infarction (MI) triggers a systemic inflammatory response
      which determines subsequent healing. Experimentally, cardiac positron emission
      tomography and magnetic resonance imaging have been used successfully to obtain
      mechanistic insights. We explored the translational potential in patients early
      after MI. METHODS AND RESULTS: Positron emission tomography/computed tomography
      and cardiac magnetic resonance were performed in 15 patients <7 days after first
      MI. Cardiac magnetic resonance showed regional transmural late gadolinium
      enhancement and edema exceeding the area of late gadolinium enhancement. Using F
      18 deoxyglucose with heparin pretreatment, metabolic rate of glucose (MRGlc) was
      significantly increased in infarct versus remote myocardium (median, 2.0 versus
      0.4 mg/min per 100 mL; P=0.0001). MRGlc in infarct correlated with remote
      myocardium (rho=0.64; P=0.01), spleen (rho=0.82; P=0.0002), and bone
      marrow(rho=0.57; P=0.03), but not with muscle or liver. Regionally, F-18
      deoxyglucose score was highest in segments with late gadolinium enhancement
      versus edema only and remote (median, 2.0 versus 1.8 versus 0.4; P<0.0001).
      Patients requiring repeat intervention during preliminary follow-up of 11+/-5
      months tended to have higher early post-MI MRGlc. Five patients with chronic,
      stable MI served as controls. Opposite to acute MI, MRGlc was lower in infarct
      (median infarct/remote ratio, 0.6 versus 3.2 for acute MI; P=0.001), and there
      was no correlation with bone marrow or spleen MRGlc. CONCLUSIONS: Increased
      glucose utilization after heparin-induced suppression of myocyte uptake appears
      to mostly reflect inflammatory activity in damaged myocardium early after MI.
      Consistent with prior preclinical observations, and in contrast to chronic MI,
      this is associated with activity in spleen and bone marrow as sources of
      inflammatory cells. Positron emission tomography and cardiac magnetic resonance
      multimodality characterization of the acutely infarcted, inflamed myocardium may
      provide multiparametric end points for clinical studies aiming at support of
      infarct healing.

PMID- 25049057
TI  - Comparative serum albumin interactions and antitumor effects of Au(III) and
      Ga(III) ions.
AB  - In the present study, interactions of Au(III) and Ga(III) ions on human serum
      albumin (HSA) were studied comparatively via spectroscopic and thermal analysis
      methods: UV-vis absorbance spectroscopy, fluorescence spectroscopy, Fourier
      transform infrared (FT-IR) spectroscopy and isothermal titration calorimetry
      (ITC). The potential antitumor effects of these ions were studied on MCF-7 cells
      via Alamar blue assay. It was found that both Au(III) and Ga(III) ions can
      interact with HSA, however; Au(III) ions interact with HSA more favorably and
      with a higher affinity. FT-IR second derivative analysis results demonstrated
      that, high concentrations of both metal ions led to a considerable decrease in
      the alpha-helix content of HSA; while Au(III) led to around 5% of decrease in the
      alpha-helix content at 200MUM, it was around 1% for Ga(III) at the same
      concentration. Calorimetric analysis gave the binding kinetics of metal-HSA
      interactions; while the binding affinity (Ka) of Au(III)-HSA binding was around
      3.87*10(5)M(-1), it was around 9.68*10(3)M(-1) for Ga(III)-HSA binding.
      Spectroscopy studies overall suggest that both metal ions have significant
      effects on the chemical structure of HSA, including the secondary structure
      alterations. Antitumor activity studies on MCF7 tumor cell line with both metal
      ions revealed that, Au(III) ions have a higher antiproliferative activity
      compared to Ga(III) ions. 

PMID- 25049058
TI  - Significance of Zn(2+) signaling in cognition: insight from synaptic Zn(2+)
      dyshomeostasis.
AB  - Zinc is concentrated in the synaptic vesicles via zinc transporter-3 (ZnT3),
      released from glutamatergic (zincergic) neuron terminals, and serves as a signal
      factor (Zn(2+) signal) in the intracellular (cytosol) compartment as well as in
      the extracellular compartment. Synaptic Zn(2+) signaling is dynamically linked to
      neurotransmission via glutamate and is involved in synaptic plasticity such as
      long-term potentiation (LTP) and cognitive activity. Zinc concentration in the
      synaptic vesicles is correlated with ZnT3 protein expression and potentially
      decreased under chronic zinc deficiency. Synaptic vesicle serves as a large pool
      for Zn(2+) signaling and other organelles might also serve as a pool for Zn(2+)
      signaling. ZnT3KO mice and zinc-deficient animals, which lack or reduce Zn(2+)
      release into the extracellular space by action potentials, are able to recognize
      novel or displaced objects normally. However, the amount of Zn(2+) functioning as
      a signal factor increases along with brain development. Exogenous Zn(2+) lowers
      the threshold in hippocampal CA1 LTP induction in young rat. Furthermore, ZnT3KO
      mice lose advanced cognition such as contextual discrimination. It is likely that
      the optimal range of synaptic Zn(2+) signaling is involved in cognitive activity.
      On the basis of the findings on the relationship between dyshomeostasis of
      synaptic Zn(2+) and cognition, this paper summarizes the possible involvement of
      intracellular Zn(2+) signaling in cognitive ability. 

PMID- 25049059
TI  - Should bioactive trace elements not recognized as essential, but with beneficial
      health effects, have intake recommendations.
AB  - Today, most nutritionists do not consider a trace element essential unless it has
      a defined biochemical function in higher animals or humans. As a result, even
      though it has been found that trace elements such as boron and silicon have
      beneficial bioactivity in higher animals and humans, they generally receive
      limited attention or mention when dietary guidelines or intake recommendations
      are formulated. Recently, the possibility of providing dietary intake
      recommendations such as an adequate intake (AI) for some bioactive food
      components (e.g., flavonoids) has been discussed. Boron, chromium, nickel, and
      silicon are bioactive food components that provide beneficial health effects by
      plausible mechanisms of action in nutritional and supra nutritional amounts, and
      thus should be included in the discussions. Although the science base may not be
      considered adequate for establishing AIs, a significant number of findings
      suggest that statements about these trace elements should be included when
      dietary intake guidance is formulated. An appropriate recommendation may be that
      diets should include foods that would provide trace elements not currently
      recognized as essential in amounts shown to reduce the risk of chronic disease
      and/or promote health and well-being. 

PMID- 25049060
TI  - Characteristics of adverse medication events in a children's hospital.
AB  - AIM: To compare adverse medication events (AMEs) reported in children, via the
      International Statistical Classification of Diseases and Related Health Problems
      10th Revision (ICD-10) coding with events reported via other data sources.
      METHOD: AME reports were retrieved using codes Y40-Y59 and X40-X44 over 6 months.
      Patients' charts were manually reviewed to identify events associated with error
      and/or harm with medicines during a hospital admission. Medication name, group,
      error, harm and alert documentation were recorded. Clinical incidents and
      pharmacist interventions were reviewed for the same period. RESULTS: Two hundred
      sixty-three events from January to June 2011 were recorded by ICD-10 coding in
      180 patients. After duplicated, missing or unrelated events were excluded and 146
      AMEs remained. In the same period, 117 AMEs were reported as incidents and 190 as
      pharmacist interventions. In total, 276 children with 447 events were reported
      via all sources. Little duplication between data sources was evident. In total,
      158 events involved harm, with 135 of these from ICD-10 coding, 16 from incident
      reports and 2 pharmacist interventions (including 6 events from multiple
      sources). Error was involved in 3% of ICD10 reports, 97% of incidents and 100% of
      interventions. Only 14% of harm-related events from ICD-10 were documented on the
      medical record clinical alert. Chemotherapy accounted for 31% of harm-related
      events, antimicrobials 18%, corticosteroids 14% and narcotics 12%. CONCLUSION: Of
      the harm-related events, 85% were documented via ICD-10 coding with few
      documented in other databases. Review of ICD-10-coded AMEs can provide valuable
      information to improve patient safety and quality.

PMID- 25049061
TI  - Studies on the kinetics of carbamazepine degradation in aqueous matrix in the
      course of modified Fenton's reactions.
AB  - The present article describes a study into the kinetics of carbamazepine
      degradation under influence of the standard Fenton's reagent, light-enhanced
      Fenton's reagent, as well as modified Fenton's systems in which iron(II) ion is
      replaced by Cu(I), Cu(II), Ni(II), Mn(II), Cr(III) and V(V) ions. In the course
      of the study it was established that V(V) ion modified Fenton's reagent was
      equally effective in relation to carbamazepine as the standard reagent.
      Parameters of both standard and modified Fenton's reagents were optimized. It was
      observed that an increased concentration of inorganic ions and acidic pH levels
      precipitated the decomposition of carbamazepine. 

PMID- 25049062
TI  - Simple strategies for fabrication of a periodic mesoporous aluminosilicate with
      crystalline walls.
AB  - An alkali-assisted cooperative assembly process of two different templating
      systems with aluminosilicate precursors is described. A highly ordered mesoporous
      zeolite with the 2D hexagonal symmetry mesospores and MFI zeolitic framework
      walls is synthesized. This method also allows the preparation of ZSM-5 with c- or
      b-axis-aligned mesopores. The materials have promising catalytic activities for
      organic reactions involving bulky molecules. 

PMID- 25049063
TI  - Nanosecond electric pulses deprive zinc ions of carboxypeptidase G2.
AB  - Nanosecond electric pulses (nsEP, 10kV/cm with a pulse duration of 8, 16 or 24ns)
      inhibited the activity of carboxypeptidase G2 (CPG2), a zinc-dependent homodimer;
      the relative activity was <20% when the total exposure time was >120s. No
      alterations were detected in electrophoresis, chromatography, mass spectroscopy
      and circular dichroism, thus demonstrating intactness of the apoenzyme.
      Inductively coupled plasma-mass spectrometry indicated that zinc levels were
      3.30MUg/mg protein in control CPG2, and decreased to 0.40, 0.12 or 0.38MUg/mg
      protein after 240s of 8-, 16- or 24-ns pulses, respectively. In CPG2 exposed to
      240s of 8-, 16- and 24-ns pulses, the reloading of zinc with redialysis recovered
      the activity to 94.7+/-3.4%, 84.0+/-5.2% and 81.7+/-7.0%, respectively (p=0.0853,
      0.0741, 0.0668). These data demonstrated that nsEP inhibited CPG2 via removal of
      zinc, and that nsEP can be used to modulate CPG2. 

PMID- 25049064
TI  - Free-standing nitrogen-doped graphene paper as electrodes for high-performance
      lithium/dissolved polysulfide batteries.
AB  - Free-standing N-doped graphene papers (NGP), generated by pyrolysis of
      polydiallyldimethylammonium chloride, were successfully used as binder-free
      electrodes for the state-of-the-art Li/polysulfide-catholyte batteries. They
      exhibited high specific capacities of approximately 1000 mA h g(-1) (based on S)
      after 100 cycles and coulombic efficiencies great than 98%, significantly better
      than undoped graphene paper (GP). These NGP were characterized with XRD, X-ray
      photoelectron spectroscopy, thermogravimetric analysis, AFM, electron microscopy,
      and Raman and impedance spectroscopy before and after cycling. Spectroscopic
      evidence suggested stronger binding of sulfide to NGP relative to GP, and
      modelling results from DFT calculation, substantiated with experimental data,
      indicated that pyrrolic and pyridinic N atoms interacted more strongly with Li
      polysulfides than quaternary N atoms. Thus, more favorable partition of
      polysulfides between the electrode and the electrolyte and the corresponding
      effect on the morphology of the passivation layer were the causes of the
      beneficial effect of N doping.

PMID- 25049065
TI  - Impact of adult congenital heart disease on survival and mortality after heart
      transplantation.
AB  - BACKGROUND: Reduced early survival has been reported in adult congenital heart
      disease (ACHD) heart transplant (HTx) recipients, but little is known about late
      outcomes after HTx. The aim of this study was to examine survival; causes of
      death; and predictors of early (<1 year), mid-term (1 to 5 years) and late (>5
      years) mortality in ACHD HTx recipients. METHODS: ACHD patients undergoing HTx
      between 1985 and 2010 were identified in the transplant registry of the
      International Society for Heart and Lung Transplantation (ISHLT). Survival was
      compared between ACHD and other adult HTx recipients ("controls") using the
      Kaplan-Meier method. Factors associated with survival beyond 1 year were assessed
      using multivariable proportional hazards regression analysis. RESULTS: Of 85,647
      adults who underwent HTx, 1,851 (2.2%) were transplanted for ACHD. Early death
      secondary due to technical reasons was high among ACHD HTx recipients: 10% vs. 4%
      in controls (p < 0.0001). However, long-term survival of ACHD recipients who
      survived the early hazard phase was superior compared with controls (p < 0.0001).
      This was in part due to a lower infection (p < 0.0001) and malignancy-related (p
      < 0.01) mortality. Cardiac re-transplantation in ACHD HTx recipients was
      associated with a 2.75-fold increase in mortality. CONCLUSION: A "survival
      paradox" exists among ACHD recipients, whose high early mortality is balanced by
      better long-term survival in those who survive the early hazard phase after HTx.
      A high mortality risk after cardiac re-transplantation in this group of patients
      suggests that this treatment option should only be considered in carefully
      selected ACHD HTx recipients.

PMID- 25049066
TI  - Neutrophil gelatinase-associated lipocalin and cystatin C for the prediction of
      clinical events in patients with advanced heart failure and after ventricular
      assist device placement.
AB  - BACKGROUND: Progressive renal dysfunction develops in patients with advanced HF.
      We evaluated neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C
      compared with established markers of renal function in patients with heart
      failure (HF) because they might improve prognostic assessment of patients with
      HF. METHODS: Serum samples were collected from 40 patients with stable HF (age:
      58 +/- 8 years, body mass index [BMI]: 28.4 +/- 6.4 kg/m(2)), 40 HF patients
      undergoing ventricular assist device (VAD) implantation (age: 53 +/- 11 years,
      BMI: 26.8 +/- 5.5 kg/m(2)), 40 patients undergoing VAD removal at cardiac
      transplantation, and 24 controls (age: 48 +/- 7 years, BMI: 29.4 +/- 4.2
      kg/m(2)). Clinical data were collected from institutional medical records. NGAL
      and cystatin C levels were measured by enzyme-linked immunosorbent assay and
      estimated glomerular filtration rate (eGFR) calculated using the Modification of
      Diet in Renal Disease formula. RESULTS: Patients with stable HF showed elevated
      NGAL and cystatin C levels compared with controls (NGAL: 114.9 +/- 48.3 ng/mL vs
      72.0 +/- 36.6 ng/mL, p < 0.0001; cystatin C: 1490.4 +/- 576.1 ng/mL vs 954.7 +/-
      414.2 ng/mL, p = 0.0026). Unlike cystatin C, NGAL increased in advanced HF
      patients requiring VAD implantation (158.7 +/- 74.8 ng/mL, p < 0.001). On VAD
      support, NGAL levels decreased (127.1 +/- 80.4 ng/mL, p = 0.034). NGAL was higher
      in patients who developed right ventricular failure (187.8 +/- 66.0 vs 130.9 +/-
      67.0 ng/mL, p = 0.03) and irreversible renal dysfunction (190.0 +/- 73.8 ng/mL vs
      133.8 +/- 54.2 ng/mL, p < 0.05), whereas cystatin C, creatinine, and eGFR were
      not different. NGAL correlated with eGFR (r = -0.2188, p = 0.01). CONCLUSIONS:
      NGAL levels correlate with HF severity and hemodynamic improvement after VAD
      placement. Our findings suggest a role of this novel biomarker as a marker of
      severity and prognosis in patients with HF.

PMID- 25049068
TI  - Three-year results of an investigator-driven multicenter, international,
      randomized open-label de novo trial to prevent BOS after lung transplantation.
AB  - BACKGROUND: Chronic lung allograft dysfunction (CLAD), predominantly manifest as
      bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and
      death after lung transplantation. We assessed the efficacy and safety of 2 de
      novo immunosuppression protocols to prevent BOS. METHODS: This was a multicenter,
      prospective, international, randomized (1:1) open-label superiority study of de
      novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD),
      both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose
      (C2) levels, and corticosteroids. Target C2 levels were lower in the RAD group
      because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction
      therapy was not used. Patients were stratified at entry for cystic fibrosis.
      Confirmation of anastomotic healing was required for randomization. Primary
      efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis.
      Secondary efficacy parameters were patient and graft survival and severity of
      rejection. Treatment failure was defined by graft loss, patient death, drug
      cessation, or need for other therapy. RESULTS: The 3-year freedom from BOS Grade
      1 was 70% for MPS (n = 80) vs 71% for RAD (n = 84; p = 0.95 by log-rank) in ITT
      but was lower in the RAD arm of the per-protocol population (p = 0.03). The 3
      year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients
      switched from MPS vs 31 from RAD (p < 0.01). Days on MPS were greater than days
      on RAD (p < 0.01). Rejection events proven by biopsy specimen were more common on
      MPS (p = 0.02), as were leucopenia (p < 0.01), diarrhea (p < 0.01), and
      cytomegalovirus infection (p = 0.04). Venous thromboembolism was more frequent on
      RAD (p = 0.02). Creatinine at 3 years was 160 +/- 112 MUmol/1iter in MPS patients
      vs 152 +/- 98 MUmol/1iter in RAD patients (p = 0.67). CONCLUSIONS: This 3-year
      ITT analysis found no significant difference between arms but was underpowered to
      accept the null hypothesis that RAD and MPS have equivalent efficacy in
      preventing BOS or death after lung transplantation.

PMID- 25049067
TI  - Treatment with inotropes and related prognosis in acute heart failure:
      contemporary data from the Italian Network on Heart Failure (IN-HF) Outcome
      registry.
AB  - BACKGROUND: In the recent Italian Network on Heart Failure (IN-HF) Outcome
      registry, including 1,855 patients with acute heart failure (AHF), we reviewed
      the use of inotropes and their prognostic implication on in-hospital and 12-month
      mortality. METHODS: IN-HF Outcome is a prospective, multicenter, observational,
      study involving 61 Italian cardiology centers. AHF patients have been enrolled
      over a 2-year period and followed-up for 1 year. Inotropes were used in 360
      patients (19.4%). RESULTS: Patients who received inotropes had a more severe
      clinical and hemodynamic profile than those who did not and exhibited a
      significantly higher rate of in-hospital (21.4% vs 2.7%, p < 0.01) and 1-year
      (50.6% vs 17.7%, p < 0.01) mortality. At entry, systolic blood pressure (SBP) was
      <= 110 mm Hg in 58%, 111 to 130 mm Hg in 24.5%, and > 130 mm Hg in 17.5%.
      Multivariable analyses showed use of inotropes was the strongest predictor of all
      cause death. These data were confirmed by propensity score analyses. According to
      SBP at entry, the 2 groups with SBP > 110 mm Hg who took inotropes, despite a
      more favorable clinical profile, exhibited a similar worse prognosis,
      particularly at 1 year: 56.3% (<= 110 mm Hg), 43.7% (111-130 mm Hg), and 40.3%
      (>130 mm Hg) vs 17.7%. CONCLUSIONS: Inotropes were used in nearly 20% of the
      patient admitted for AHF, and this treatment was associated with a short-term to
      medium-term poor prognosis. An inappropriate use of inotropes in patients with
      normal to high SBP, and presumably preserved cardiac output, may have
      significantly contributed to affect the all-group outcome.

PMID- 25049069
TI  - Stress management skills, cortisol awakening response, and post-exertional
      malaise in Chronic Fatigue Syndrome.
AB  - Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue
      typically exacerbated by cognitive and/or physical exertion, referred to as post
      exertional malaise (PEM). In a variety of populations, the cortisol awakening
      response (CAR) has stood out as a marker of endocrine dysregulation relevant to
      the experience of fatigue, and may therefore be particularly relevant in CFS.
      This is the first study to examine PEM and the CAR in a sample of individuals
      with CFS. The CAR has also been established as a stress-sensitive measure of HPA
      axis functioning. It follows that better management of stress could modulate the
      CAR, and in turn PEM. In this cross-sectional study, we hypothesized that greater
      Perceived Stress Management Skills (PSMS) would relate to lower reports of PEM,
      via the impact of PSMS on the CAR. A total of 117 adults (72% female) with a CFS
      diagnosis completed self-report measures of PSMS and PEM symptomatology and a two
      day protocol of saliva collection. Cortisol values from awakening and 30 min post
      awakening were used to compute the CAR. Regression analyses revealed that greater
      PSMS related to greater CAR and greater CAR related to less PEM severity.
      Bootstrapped analyses revealed an indirect effect of PSMS on PEM via the CAR,
      such that greater PSMS related to less PEM, via a greater CAR. Future research
      should examine these trends longitudinally and whether interventions directed at
      improving stress management skills are accompanied by improved cortisol
      regulation and less PEM in individuals with CFS.

PMID- 25049070
TI  - Re-analysis of the association between perinatal androgens and pragmatic language
      ability.

PMID- 25049071
TI  - Our recent progress on the intramolecular Diels-Alder reaction approach in
      natural products synthesis: synthetic studies of the octahydronaphthalene
      substructure of versipelostatins and the A/B/C-tricyclic substructure of
      GKK1032s.
AB  - During this decade, the enantio- and stereoselective synthesis of natural
      products has been actively explored in the author's laboratory. In this account,
      the author outlines practical syntheses of the polycyclic substructures of two
      novel structurally formidable antibiotics, namely, the trans-fused
      octahydronaphthalene moiety of versipelostatins and the A/B/C-tricyclic
      decahydrofluorene moiety of GKK1032s. Both syntheses have been achieved with
      remarkable regio- and stereoselectivity via intramolecular Diels-Alder reactions
      using well-designed enantiomeric substrates. 

PMID- 25049072
TI  - A deformable atlas of the laboratory mouse.
AB  - PURPOSE: This paper presents a deformable mouse atlas of the laboratory mouse
      anatomy. This atlas is fully articulated and can be positioned into arbitrary
      body poses. The atlas can also adapt body weight by changing body length and fat
      amount. PROCEDURES: A training set of 103 micro-CT images was used to construct
      the atlas. A cage-based deformation method was applied to realize the articulated
      pose change. The weight-related body deformation was learned from the training
      set using a linear regression method. A conditional Gaussian model and thin-plate
      spline mapping were used to deform the internal organs following the changes of
      pose and weight. RESULTS: The atlas was deformed into different body poses and
      weights, and the deformation results were more realistic compared to the results
      achieved with other mouse atlases. The organ weights of this atlas matched well
      with the measurements of real mouse organ weights. This atlas can also be
      converted into voxelized images with labeled organs, pseudo CT images and
      tetrahedral mesh for phantom studies. CONCLUSIONS: With the unique ability of
      articulated pose and weight changes, the deformable laboratory mouse atlas can
      become a valuable tool for preclinical image analysis.

PMID- 25049073
TI  - Gallium-68-labeled anti-HER2 single-chain Fv fragment: development and in vivo
      monitoring of HER2 expression.
AB  - PURPOSE: We aimed to develop a gallium-68 (Ga-68)-labeled single-chain variable
      fragment (scFv) targeting the human epidermal growth factor receptor 2 (HER2) to
      rapidly and noninvasively evaluate the status of HER2 expression. PROCEDURES:
      Anti-HER2 scFv was labeled with Ga-68 by using deferoxamine (Df) as a
      bifunctional chelate. Biodistribution of [(68)Ga]Df-anti-HER2 scFv was examined
      with tumor-bearing mice and positron emission tomography (PET) imaging was
      performed. The changes in HER2 expression after anti-HER2 therapy were monitored
      by PET imaging. RESULTS: [(68)Ga]Df-anti-HER2 scFv was obtained with high
      radiochemical yield after only a 5-min reaction at room temperature. The probe
      showed high accumulation in HER2-positive xenografts and the intratumoral
      distribution of radioactivity coincided with HER2-positive regions. Furthermore,
      [(68)Ga]Df-anti-HER2 scFv helped visualize HER2-positive xenografts and monitor
      the changes in HER2 expression after anti-HER2 therapy. CONCLUSION: [(68)Ga]Df
      anti-HER2 scFv could be a promising probe to evaluate HER2 status by in vivo PET
      imaging, unless trastuzumab is prescribed as part of the therapy.

PMID- 25049074
TI  - Differential dopamine receptor subtype regulation of adenylyl cyclases in lipid
      rafts in human embryonic kidney and renal proximal tubule cells.
AB  - Dopamine D1-like receptors (D1R and D5R) stimulate adenylyl cyclase (AC)
      activity, whereas the D2-like receptors (D2, D3 and D4) inhibit AC activity. D1R,
      but not the D5R, has been reported to regulate AC activity in lipid rafts (LRs).
      We tested the hypothesis that D1R and D5R differentially regulate AC activity in
      LRs using human embryonic kidney (HEK) 293 cells heterologously expressing human
      D1 or D5 receptor (HEK-hD1R or HEK-hD5R) and human renal proximal tubule (hRPT)
      cells that endogenously express D1R and D5R. Of the AC isoforms expressed in HEK
      and hRPT cells (AC3, AC5, AC6, AC7, and AC9), AC5/6 was distributed to a greater
      extent in LRs than non-LRs in HEK-hD1R (84.5+/-2.3% of total), HEK-hD5R (68.9+/
      3.1% of total), and hRPT cells (66.6 +/- 2.2% of total) (P<0.05, n=4/group). In
      HEK-hD1R cells, the D1-like receptor agonist fenoldopam (1 MUM/15 min) increased
      AC5/6 protein (+17.2 +/- 3.9% of control) in LRs but decreased it in non-LRs (
      47.3+/-5.3% of control) (P<0.05, vs. control, n=4/group). By contrast, in HEK
      hD5R cells, fenoldopam increased AC5/6 protein in non-LRs (+67.1 +/- 5.3% of
      control, P<0.006, vs. control, n=4) but had no effect in LRs. In hRPT cells,
      fenoldopam increased AC5/6 in LRs but had little effect in non-LRs. Disruption of
      LRs with methyl-beta-cyclodextrin decreased basal AC activity in HEK-D1R (-94.5
      +/- 2.0% of control) and HEK-D5R cells (-87.1 +/- 4.6% of control) but increased
      it in hRPT cells (6.8+/-0.5-fold). AC6 activity was stimulated to a greater
      extent by D1R than D5R, in agreement with the greater colocalization of AC5/6
      with D1R than D5R in LRs. We conclude that LRs are essential not only for the
      proper membrane distribution and maintenance of AC5/6 activity but also for the
      regulation of D1R- and D5R-mediated AC signaling.

PMID- 25049076
TI  - Homo- and hetero-oligomerization of beta2-adrenergic receptor in receptor
      trafficking, signaling pathways and receptor pharmacology.
AB  - The beta2-adrenergic receptor (beta2AR) is the prototypic member of G protein
      coupled receptors (GPCRs) involved in the production of physiological responses
      to adrenaline and noradrenaline. Research done in the past few years vastly
      demonstrated that beta2AR can form homo- and hetero-oligomers. Despite the fact
      that currently this phenomenon is widely accepted, the spread and relevance of
      beta2AR oligomerization are still a matter of debate. This review considers the
      progress achieved in the field of beta2AR oligomerization with focus on the
      implications of the receptor-receptor interactions to beta2AR trafficking,
      pharmacology and downstream signal transduction pathways. 

PMID- 25049075
TI  - Hs3st-A and Hs3st-B regulate intestinal homeostasis in Drosophila adult midgut.
AB  - Intrinsic and extrinsic signals as well as the extracellular matrix (ECM) tightly
      regulate stem cells for tissue homeostasis and regenerative capacity. Little is
      known about the regulation of tissue homeostasis by the ECM. Heparan sulfate
      proteoglycans (HSPGs), important components of the ECM, are involved in a variety
      of biological events. Two heparin sulfate 3-O sulfotransferase (Hs3st) genes,
      Hs3st-A and Hs3st-B, encode the modification enzymes in heparan sulfate (HS)
      biosynthesis. Here we demonstrate that Hs3st-A and Hs3st-B are required for adult
      midgut homeostasis. Depletion of Hs3st-A in enterocytes (ECs) results in
      increased intestinal stem cell (ISC) proliferation and tissue homeostasis loss.
      Moreover, increased ISC proliferation is also observed in Hs3st-B null mutant
      alone, or in combination with Hs3st-A RNAi. Hs3st-A depletion-induced ISC
      proliferation is effectively suppressed by simultaneous inhibition of the EGFR
      signaling pathway, suggesting that tissue homeostasis loss in Hs3st-A-deficient
      intestines is due to increased EGFR signaling. Furthermore, we find that Hs3st-A
      depleted ECs are unhealthy and prone to death, while ectopic expression of the
      antiapoptotic p35 is able to greatly suppress tissue homeostasis loss in these
      intestines. Together, our data suggest that Drosophila Hs3st-A and Hs3st-B are
      involved in the regulation of ISC proliferation and midgut homeostasis
      maintenance.

PMID- 25049077
TI  - Ghrelin suppresses Purkinje neuron P-type Ca(2+) channels via growth hormone
      secretagogue type 1a receptor, the betagamma subunits of Go-protein, and protein
      kinase a pathway.
AB  - Although ghrelin receptors have been demonstrated to be widely expressed in the
      central nervous system and peripheral tissues of mammals, it is still unknown
      whether ghrelin functions in cerebellar Purkinje neurons. In this study, we
      identified a novel functional role for ghrelin in modulating P-type Ca(2+)
      channel (P-type channel) currents (IBa) as well as action-potential firing in rat
      Purkinje neurons. Our results show that ghrelin at 0.1MUM reversibly decreased
      IBa by ~32.3%. This effect was growth hormone secretagogue receptor 1a (GHS-R1a)
      dependent and was associated with a hyperpolarizing shift in the voltage
      dependence of inactivation. Intracellular application of GDP-beta-S and
      pretreatment with pertussis toxin abolished the inhibitory effects of ghrelin.
      Dialysis of cells with the peptide QEHA (but not the scrambled peptide SKEE), and
      a selective antibody raised against the G-protein alphao subunit both blocked the
      ghrelin-induced response. Ghrelin markedly increased protein kinase A (PKA)
      activity, and intracellular application of PKI 5-24 as well as pretreatment of
      the cells with the PKA inhibitor KT-5720 abolished ghrelin-induced IBa decrease,
      while inhibition of PKC had no such effects. At the cellular level, ghrelin
      induced a significant increase in action-potential firing, and blockade of GHS
      R1a by BIM-28163 abolished the ghrelin-induced hyperexcitability. In summary,
      these results suggest that ghrelin markedly decreases IBa via the activation of
      GHS-R1a, which is coupled sequentially to the activities of Go-protein betagamma
      subunits and the downstream PKA pathway. This could contribute to its
      physiological functions, including the spontaneous firing of action potentials in
      cerebellar Purkinje neurons.

PMID- 25049078
TI  - MicroRNA-200a controls Nrf2 activation by target Keap1 in hepatic stellate cell
      proliferation and fibrosis.
AB  - Hepatic fibrosis is a common final pathological process in the progression of
      liver disease, which is primarily due to oxidative stress. Nrf2 is known to
      coordinate induction of genes that encode antioxidant enzymes. Moreover, Nrf2
      expression is largely regulated through the association of Nrf2 with Keap1, which
      results in cytoplasmic Nrf2 degradation. Conversely, little is known concerning
      the regulation of Keap1 expression. Although the function of miRNA-200a controls
      Keap1 gene expression has been discussed in many cancers and fibrotic diseases,
      its role in hepatic fibrosis is still poorly understood. By using miRNA mimic, we
      observed miRNA-200a silencing in activated hepatic stellate cell and demonstrated
      that upon re-expression, miRNA-200a targets the Keap1, and leading to Keap1 mRNA
      degradation. We find that treatment with miRNA-200a mimics, restored miRNA-200a
      expression and reduced Keap1 levels. This reduction in Keap1 levels corresponded
      with Nrf2 nuclear translocation and activation of Nrf2-dependent NQO1 gene
      transcription. Moreover, we found that Nrf2 activation inhibited the TGF-beta1
      independent growth of hepatic stellate cell. Finally, our study demonstrates that
      miRNA-200a regulates the Keap1/Nrf2 pathway in hepatic stellate cell and
      fibrosis, and we find that epigenetic therapy can restore miRNA-200a regulation
      of Keap1 expression, therefore reactivating the Nrf2-dependent antioxidant
      pathway in liver fibrosis.

PMID- 25049079
TI  - Nuclear translocation of CBP/p300-interacting protein CITED1 induced by
      parathyroid hormone requires serine phosphorylation at position 79 in its 63-84
      domain.
AB  - The transcriptional cofactor CITED1 inhibits osteoblastic differentiation and
      blunts the stimulation of osteoblastic differentiation by parathyroid hormone
      (PTH). In the MC3T3-E1 osteoblastic cell line, we found that CITED1 was located
      predominantly in the cytoplasm and that hPTH(1-34) increased translocation of
      CITED1 from the cytoplasm to the nucleus. This response to hPTH(1-34) was not
      observed when all 9 serine residues within the 63-84 domain of CITED1 were
      mutated to alanines (CITED1 9S>A) or when a single serine to alanine mutation was
      made at position 79 (CITED1 S(79)>A). CITED1 containing mutations of these 9
      serines to glutamic acid (9S>E) retained the same nuclear translocation response
      to hPTH(1-34) as the wild type CITED1. ALP activity and formation of mineralized
      nodules were inhibited in cells transfected with pcDNA3-CFP-CITED1 or with pcDNA3
      CFP-CITED1 9S>E with or without hPTH(1-34) treatment (all P<0.05); these changes
      were not observed using CITED1 9S>A. Cells exposed to intermittent treatment with
      hPTH(1-34) expressed more ALP2, Runx2 and osteocalcin than vehicle-treated cells.
      These effects of hPTH(1-34) were inhibited in cells transfected with pcDNA3-CFP
      CITED1 or pcDNA3-CFP-CITED1 9S>E, but were slightly enhanced by the alanine
      mutants. PKC activator (TPA) increased nuclear translocation of CITED1, whereas a
      PKC inhibitor (Go6983) blunted the effect of hPTH(1-34) on the nuclear
      translocation of wildtype CITED1 but not of CITED1 S(79)>E. The data indicated
      that serine phosphorylation at position 79 in the 63-84 domain is associated with
      PKC activation, and is required for both CITED1 nuclear translocation induced by
      PTH and the negative effects of CITED1 on osteoblastic differentiation and
      mineralization.

PMID- 25049080
TI  - Insight into the therapeutic aspects of 'Zeta-Chain Associated Protein Kinase 70
      kDa' inhibitors: a review.
AB  - Zeta-Chain Associated Protein Kinase 70 kDa (ZAP-70), a member of Syk family (non
      receptor protein tyrosine kinase family), has an imperative function in the
      immune cell signaling in T cells. Its role in T-cell development has been
      established by the severe combined immune deficiency syndrome in ZAP-70 deficient
      humans. Moreover, defects in T-cell activation and downstream signaling events
      were observed in T-cells that lack ZAP-70. Thus, the crucial role of ZAP-70 in
      the development and activation of T-cell and its predominant expression in T
      cells make it a logical target for the treatment of pathological conditions
      related to abnormal T-cell responses. The present review article portrays the
      domain structure of ZAP-70 along with its implication in T-cell signaling.
      Additionally, varied ZAP-70 inhibitors published in different patents and papers
      have also been reviewed.

PMID- 25049081
TI  - The catalytic triad of testes-specific protease 50 (TSP50) is essential for its
      function in cell proliferation.
AB  - Testes-specific protease 50 (TSP50) is a novelly identified pro-oncogene and it
      shares a similar enzymatic structure with many serine proteases. Our previous
      results suggested that TSP50 could promote tumorigenesis through degradation of
      IkappaBalpha protein and activating NF-kappaB signaling, and the threonine
      mutation in its catalytic triad could depress TSP50-mediated cell proliferation.
      However, whether the two other residues in the catalytic triad of TSP50 play a
      role in maintaining protease activity and tumorigenesis, and the mechanisms
      involved in this process remain unclear. Here, we constructed and characterized
      three catalytic triad mutants of TSP50 and found that all the mutants could
      significantly depress TSP50-induced cell proliferation and colony formation in
      vitro and tumor formation in vivo, and the aspartic acid at position 206 in the
      catalytic triad played a more crucial role than threonine and histidine in this
      process. Mechanistic studies revealed that the mutants in the catalytic triad
      abolished the enzyme activity of TSP50, but did not change the cellular
      localization. Furthermore, our data indicated that all the three mutants
      suppressed activation of NF-kappaB signal by preventing the interaction between
      TSP50 and the NF-kappaB:IkappaBalpha complex. Most importantly, we demonstrated
      that TSP50 could interact with IkappaBalpha protein and cleave it directly as a
      new protease in vitro.

PMID- 25049082
TI  - The phosphatidylinositol(4,5)bisphosphate-binding sequence of transient receptor
      potential channel canonical 4alpha is critical for its contribution to
      cardiomyocyte hypertrophy.
AB  - Cardiomyocyte hypertrophy requires a source of Ca(2+) distinct from the Ca(2+)
      that regulates contraction. The canonical transient receptor potential channel
      (TrpC) family, a family of cation channels regulated by activation of
      phospholipase C (PLC), has been implicated in this response. Cardiomyocyte
      hypertrophy downstream of Gq-coupled receptors is mediated specifically by
      PLCbeta1b that is scaffolded onto a SH3 and ankyrin repeat protein 3 (Shank3)
      complex at the sarcolemma. TrpC4 exists as two splice variants (TrpC4alpha and
      TrpC4beta) that differ only in an 84-residue sequence that binds to
      phosphatidylinositol(4,5)bisphosphate (PIP2), the substrate of PLCbeta1b. In
      neonatal rat cardiomyocytes, TrpC4alpha, but not TrpC4beta, coimmunoprecipitated
      with both PLCbeta1b and Shank3. Heightened PLCbeta1b expression caused
      TrpC4alpha, but not TrpC4beta, translocation to the sarcolemma, where it
      colocalized with PLCbeta1b. When overexpressed in cardiomyocytes, TrpC4alpha, but
      not TrpC4beta, increased cell area (893 +/- 18 to 1497 +/- 29 mm(2), P < 0.01)
      and marker gene expression (atrial natriuretic peptide increased by 409 +/- 32%,
      and modulatory calcineurin inhibitory protein 1 by 315 +/- 28%, P < 0.01).
      Dominant-negative TrpC4 reduced hypertrophy initiated by PLCbeta1b, or PLCbeta1b
      coupled receptor activation, by 72 +/- 8% and 39 +/- 5 %, respectively. We
      conclude that TrpC4alpha is selectively involved in mechanisms downstream of
      PLCbeta1b culminating in cardiomyocyte hypertrophy, and that the hypertrophic
      response is dependent on the TrpC4alpha splice variant-specific sequence that
      binds to PIP2. 

PMID- 25049083
TI  - Catalytic enantioselective amide allylation of isatins and its application in the
      synthesis of 2-oxindole derivatives spiro-fused to the alpha-methylene-gamma
      butyrolactone functionality.
AB  - This article is a full account of the work exploring the potential utility of
      catalytic enantioselective amide allylation of various isatins using indium-based
      chiral catalysts. A survey of various isatin substrates and NH-containing
      stannylated reagents revealed that the reaction has a remarkably wide scope to
      result in extremely high yields and enantioselectivities (up to >99 %, 99 % ee)
      of variously substituted homoallylic alcohols. Several mechanistic investigations
      demonstrated that the substrate-reagent hydrogen-bond interaction plays a
      critical role in the formation of the key transition states to result in enhanced
      catalytic reaction. The success of this approach allowed convenient access to
      chiral 2-oxindoles spiro-fused to the alpha-methylene-gamma-butyrolactone
      functionality and their halogenated derivatives in almost enantiopure forms, thus
      highlighting the general utility of this synthetic method to deliver a large
      variety of antineoplastic drug candidates and pharmaceutically meaningful
      compounds. 

PMID- 25049084
TI  - Drug eluting devices for critically ill patients: can we apply lessons learned
      from the treatment of peripheral artery disease?
AB  - OBJECTIVE: To review the use of drug-eluting devices in peripheral arteries of
      critically ill patients FINDINGS: Drug eluting stents and drug coated balloons
      are promising technologies and have become an important tool for the endovascular
      treatment of peripheral artery disease. The concept of local drug delivery to
      prevent restenosis due to intimal hyperplasia has been proven in several trials
      for different peripheral vascular beds. Especially for the treatment of patients
      with critical lower limb ischemia, improved patency could presumably improve
      wound healing, survival and limb salvage rates. However, until now, there is a
      paucity of evidence regarding these devices in critically ill patients and
      lessons learned must be extrapolated from non-critically ill patients at this
      time. CONCLUSIONS: Restenosis rates can be reduced by drug eluting devices.
      Further study of the clinical impact of the use of drug eluting devices in the
      peripheral arteries will be required to determine if improved patency rates also
      can be translated into clinical benefit for critically ill patients.

PMID- 25049086
TI  - The spatial and temporal variation of the distribution and prevalence of Atlantic
      salmon reovirus (TSRV) infection in Tasmania, Australia.
AB  - Atlantic salmon reovirus (TSRV) has been consistently isolated from Atlantic
      salmon in Tasmania, since first identification in 1990 under the Tasmanian
      Salmonid Health Surveillance Program (TSHSP). The distribution and prevalence of
      TSRV was identified using TSHSP data. A data set of 730 fish submissions tested
      over a period of 15 years was reviewed and analysed to describe the spatial and
      temporal variation of TSRV in Tasmanian salmonid aquaculture production units.
      The virus was present throughout Tasmania with the highest reported prevalence of
      the virus in the south-east region of Tasmania. 

PMID- 25049085
TI  - Coaxing stem cells for skeletal muscle repair.
AB  - Skeletal muscle has a tremendous ability to regenerate, attributed to a well
      defined population of muscle stem cells called satellite cells. However, this
      ability to regenerate diminishes with age and can also be dramatically affected
      by multiple types of muscle diseases, or injury. Extrinsic and/or intrinsic
      defects in the regulation of satellite cells are considered to be major
      determinants for the diminished regenerative capacity. Maintenance and
      replenishment of the satellite cell pool is one focus for muscle regenerative
      medicine, which will be discussed. There are other sources of progenitor cells
      with myogenic capacity, which may also support skeletal muscle repair. However,
      all of these myogenic cell populations have inherent difficulties and challenges
      in maintaining or coaxing their derivation for therapeutic purpose. This review
      will highlight recent reported attributes of these cells and new bioengineering
      approaches to creating a supply of myogenic stem cells or implants applicable for
      acute and/or chronic muscle disorders. 

PMID- 25049087
TI  - Cochlin in normal middle ear and abnormal middle ear deposits in DFNA9 and Coch
      (G88E/G88E) mice.
AB  - DFNA9 sensorineural hearing loss and vestibular disorder, caused by mutations in
      COCH, has a unique identifying histopathology including prominent acellular
      deposits in cochlear and vestibular labyrinths. A recent study has shown presence
      of deposits also in middle ear structures of DFNA9-affected individuals (McCall
      et al., J Assoc Res Otolaryngol 12:141-149, 2004). To investigate the possible
      role of cochlin in the middle ear and in relation to aggregate formation, we
      evaluated middle ear histopathology in our Coch knock-in (Coch (G88E/G88E) )
      mouse model, which harbors one of the DFNA9-causative mutations. Our findings
      reveal accumulation of acellular deposits in the incudomalleal and
      incudostapedial joints in Coch (G88E/G88E) mice, similar to those found in human
      DFNA9-affected temporal bones. Aggregates are absent in negative control Coch
      (+/+) and Coch (-/-) mice. Thickening of the tympanic membrane (TM) found in
      humans with DFNA9 was not appreciably detected in Coch (G88E/G88E) mice at the
      evaluated age. We investigated cochlin localization first in the Coch (+/+)mouse
      and in normal human middle ears, and found prominent and specific cochlin
      staining in the incudomalleal joint, incudostapedial joint, and the pars tensa of
      the TM, which are the three sites where abnormal deposits are detected in DFNA9
      affected middle ears. Cochlin immunostaining of Coch (G88E/G88E) and DFNA9
      affected middle ears showed mutant cochlin localization within areas of
      aggregates. Cochlin staining was heterogeneous throughout DFNA9 middle ear
      deposits, which appear as unorganized and overlapping mixtures of both
      eosinophilic and basophilic substances. Immunostaining for type II collagen
      colocalized with cochlin in pars tensa of the tympanic membrane. In contrast,
      immunostaining for type II collagen did not overlap with cochlin in
      interossicular joints, where type II collagen was localized in the region of the
      chondrocytes, but not in the thin layer of the articular surface of the ossicles
      nor in the eosinophilic deposits with specific cochlin staining. 

PMID- 25049088
TI  - Escherichia coli genes and pathways involved in surviving extreme exposure to
      ionizing radiation.
AB  - To further an improved understanding of the mechanisms used by bacterial cells to
      survive extreme exposure to ionizing radiation (IR), we broadly screened
      nonessential Escherichia coli genes for those involved in IR resistance by using
      transposon-directed insertion sequencing (TraDIS). Forty-six genes were
      identified, most of which become essential upon heavy IR exposure. Most of these
      were subjected to direct validation. The results reinforced the notion that
      survival after high doses of ionizing radiation does not depend on a single
      mechanism or process, but instead is multifaceted. Many identified genes affect
      either DNA repair or the cellular response to oxidative damage. However,
      contributions by genes involved in cell wall structure/function, cell division,
      and intermediary metabolism were also evident. About half of the identified genes
      have not previously been associated with IR resistance or recovery from IR
      exposure, including eight genes of unknown function. 

PMID- 25049089
TI  - Subcellular localization and clues for the function of the HetN factor
      influencing heterocyst distribution in Anabaena sp. strain PCC 7120.
AB  - In the filamentous cyanobacterium Anabaena sp. strain PCC 7120, heterocysts are
      formed in the absence of combined nitrogen, following a specific distribution
      pattern along the filament. The PatS and HetN factors contribute to the
      heterocyst pattern by inhibiting the formation of consecutive heterocysts. Thus,
      inactivation of any of these factors produces the multiple contiguous heterocyst
      (Mch) phenotype. Upon N stepdown, a HetN protein with its C terminus fused to a
      superfolder version of green fluorescent protein (sf-GFP) or to GFP-mut2 was
      observed, localized first throughout the whole area of differentiating cells and
      later specifically on the peripheries and in the polar regions of mature
      heterocysts, coinciding with the location of the thylakoids. Polar localization
      required an N-terminal stretch comprising residues 2 to 27 that may represent an
      unconventional signal peptide. Anabaena strains expressing a version of HetN
      lacking this fragment from a mutant gene placed at the native hetN locus
      exhibited a mild Mch phenotype. In agreement with previous results, deletion of
      an internal ERGSGR sequence, which is identical to the C-terminal sequence of
      PatS, also led to the Mch phenotype. The subcellular localization in heterocysts
      of fluorescence resulting from the fusion of GFP to the C terminus of HetN
      suggests that a full HetN protein is present in these cells. Furthermore, the
      full HetN protein is more conserved among cyanobacteria than the internal ERGSGR
      sequence. These observations suggest that HetN anchored to thylakoid membranes in
      heterocysts may serve a function besides that of generating a regulatory (ERGSGR)
      peptide. 

PMID- 25049091
TI  - Bacterial nonhomologous end joining requires teamwork.
AB  - All living organisms must repair DNA double-stranded breaks (DSBs) in order to
      survive. Many bacteria rely on nonhomologous end joining (NHEJ) when only a
      single copy of the genome is available and maintain NHEJ pathways with a minimum
      of two proteins. In this issue, Bhattarai and colleagues identify additional
      factors that can work together to aid in survival of stationary-phase cells with
      chromosomal breaks. 

PMID- 25049090
TI  - Crystal structure of PhnF, a GntR-family transcriptional regulator of phosphate
      transport in Mycobacterium smegmatis.
AB  - Bacterial uptake of phosphate is usually accomplished via high-affinity
      transporters that are commonly regulated by two-component systems, which are
      activated when the concentration of phosphate is low. Mycobacterium smegmatis
      possesses two such transporters, the widely distributed PstSCAB system and
      PhnDCE, a transporter that in other bacteria mediates the uptake of alternative
      phosphorus sources. We previously reported that the transcriptional regulator
      PhnF controls the production of the Phn system, acting as a repressor under high
      phosphate conditions. Here we show that the phnDCE genes are common among
      environmental mycobacteria, where they are often associated with phnF-like genes.
      In contrast, pathogenic mycobacteria were not found to encode Phn-like systems
      but instead were found to possess multiple copies of the pst genes. A detailed
      biochemical analysis of PhnF binding to its identified binding sites in the phnD
      phnF intergenic region of M. smegmatis has allowed us to propose a quantitative
      model for repressor binding, which shows that a PhnF dimer binds independently to
      each site. We present the crystal structure of M. smegmatis PhnF at 1.8-A
      resolution, showing a homodimer with a helix-turn-helix N-terminal domain and a C
      terminal domain with a UbiC transcription regulator-associated fold. The C
      terminal domain crystallized with a bound sulfate ion instead of the so far
      unidentified physiological ligand, allowing the identification of residues
      involved in effector binding. Comparison of the positioning of the DNA binding
      domains in PhnF with that in homologous proteins suggests that its DNA binding
      activity is regulated via a conformational change in the linker region,
      triggering a movement of the N-terminal domains. 

PMID- 25049092
TI  - FurC regulates expression of zupT for the central zinc importer ZupT of
      Cupriavidus metallidurans.
AB  - The zinc importer ZupT is required for the efficient allocation of zinc to zinc
      dependent proteins in the metal-resistant bacterium Cupriavidus metallidurans but
      not for zinc import per se. The expression of zupT is upregulated under
      conditions of zinc starvation. C. metallidurans contains three members of the Fur
      family of regulators that qualify as candidates for the zupT regulator. The
      expression of a zupT-lacZ reporter gene fusion was strongly upregulated in a
      DeltafurC mutant but not in a DeltafurA or DeltafurB mutant. Expression of the
      genes for transition-metal importers (pitA, corA1, corA2, and corA3) was not
      changed in this pattern in all three Deltafur mutants, but they were still
      downregulated under conditions of elevated zinc concentrations, indicating the
      presence of another zinc-dependent regulator. FurA was a central regulator of the
      iron metabolism in C. metallidurans, and furA was constitutively expressed under
      the conditions tested. Expression of furB was upregulated under conditions of
      iron starvation, and FurB could be an iron starvation Fur connecting general
      metal and iron homeostasis, as indicated by the phenotype of a DeltafurB
      DeltafurC double mutant. FurC was purified as a Strep-tagged protein and retarded
      the electrophoretic mobility of a DNA fragment upstream of zupT. Binding of FurC
      to this operator region was influenced by the presence of zinc ions and EDTA.
      Thus, FurC is the main zinc uptake regulator (Zur) of C. metallidurans and
      represses synthesis of the central zinc importer ZupT when sufficient zinc is
      present. 

PMID- 25049094
TI  - Photodynamic therapy in China: Over 25 years of unique clinical experience Part
      two-Clinical experience.
AB  - Photodynamic therapy (PDT) was started in the People's Republic of China in the
      early 1980s after domestically produced hematoporphyrin derivative (HpD) became
      available. Since then, numerous photosensitizers have been synthesized and
      evaluated. Several promising ones have undergone clinical investigations and a
      few have entered into formal clinical trials. Various lasers and non-coherent
      light sources have been developed in China to facilitate domestic
      photosensitizers and clinical PDT applications. Chinese pioneered PDT protocols
      for treating nasopharyngeal carcinoma (NPC), liver carcinoma, port-wine stains
      (PWS) and urethral condylomata acuminata. Over the past 25 years Chinese
      physicians have treated several thousands patients, gained substantial experience
      in both basic sciences and clinical applications, and generated a great number of
      clinical reports. The Part One of this article provides an objective overview on
      China's PDT history and an introduction of domestic photosensitizers. This
      article (Part Two) will summarize clinical PDT data of nasopharyngeal carcinoma,
      liver cancer and port-wine stains since these data are clinically valuable but
      less well known outside China. 

PMID- 25049095
TI  - The new paradigm: Photodynamic therapy for the eradication of Barrett's dysplasia
      and cancer-Sufficiency versus efficiency.

PMID- 25049096
TI  - Bare fiber photodynamic therapy using porfimer sodium for esophageal disease.
AB  - During Digestive Disease Week 2005 in Chicago, Illinois, our group of 10
      gastrointestinal photodynamic therapists met to discuss variations in procedural
      technique and treatment protocols. An extensive review of the use of photodynamic
      therapy (PDT) for esophageal disease has recently been published elsewhere
      [Wolfsen HC. Present status of photodynamic therapy for high-grade dysplasia in
      Barrett's esophagus. J Clin Gastroenterol 2005;39(3):189-202]. This report, based
      mostly on clinical experience and common sense rather than evidence-based
      medicine, is a detailed discussion of pragmatic issues. In summary, our centers
      treat patients with Barrett's dysplasia, Barrett's or squamous cell carcinoma
      using the photosensitizer porfimer sodium (2mg/kg total body weight) and bare
      fiber PDT (no fiber centering devices). Aggressive suppression of gastric acid is
      uniformly emphasized. The most common technique variables were the light energy
      source, light dosimetry and the amount of Barrett's mucosa treated during a
      course of PDT. Standardization of porfimer sodium PDT procedures and light
      dosimetry may enhance treatment outcomes. 

PMID- 25049093
TI  - The phosphatidyl-myo-inositol mannosyltransferase PimA is essential for
      Mycobacterium tuberculosis growth in vitro and in vivo.
AB  - The cell envelope of Mycobacterium tuberculosis contains glycans and lipids of
      peculiar structure that play prominent roles in the biology and pathogenesis of
      tuberculosis. Consequently, the chemical structure and biosynthesis of the cell
      wall have been intensively investigated in order to identify novel drug targets.
      Here, we validate that the function of phosphatidyl-myo-inositol
      mannosyltransferase PimA is vital for M. tuberculosis in vitro and in vivo. PimA
      initiates the biosynthesis of phosphatidyl-myo-inositol mannosides by
      transferring a mannosyl residue from GDP-Man to phosphatidyl-myo-inositol on the
      cytoplasmic side of the plasma membrane. To prove the essential nature of pimA in
      M. tuberculosis, we constructed a pimA conditional mutant by using the TetR-Pip
      off system and showed that downregulation of PimA expression causes
      bactericidality in batch cultures. Consistent with the biochemical reaction
      catalyzed by PimA, this phenotype was associated with markedly reduced levels of
      phosphatidyl-myo-inositol dimannosides, essential structural components of the
      mycobacterial cell envelope. In addition, the requirement of PimA for viability
      was clearly demonstrated during macrophage infection and in two different mouse
      models of infection, where a dramatic decrease in viable counts was observed upon
      silencing of the gene. Notably, depletion of PimA resulted in complete clearance
      of the mouse lungs during both the acute and chronic phases of infection.
      Altogether, the experimental data highlight the importance of the phosphatidyl
      myo-inositol mannoside biosynthetic pathway for M. tuberculosis and confirm that
      PimA is a novel target for future drug discovery programs. 

PMID- 25049097
TI  - Endoscopic photodynamic therapy (PDT) for oesophageal cancer.
AB  - Endoscopic photodynamic therapy (PDT) is undertaken only when tumour is visible
      endoscopically with malignancy biopsy confirmed. Patients will be either Group A:
      inoperable cases with locally advanced cancer when the aim is palliation of
      dysphagia, or Group E: patients with early stage I-II disease who are unsuitable
      for surgery or decline operation, when the intent is curative. Following
      assessment for suitability for PDT and counselling, Photofrin 2mg/(kgbw) is
      administered 24-72h before endoscopic illumination using a Diode 630nm laser.
      Illumination may be either interstitial or intraluminal at a dose of 100-200J/cm.

PMID- 25049098
TI  - Photodynamic therapy for Barrett's oesophagus and oesophageal carcinoma-How I do
      it.
AB  - We have considerable experience in the use of both ALA and Photofrin-induced
      photodynamic therapy in the treatment of Barrett's oesophagus (with and without
      dysplasia) and both early and advanced oesophageal carcinoma. The drugs used and
      the techniques vary depending on the condition being treated. The techniques and
      doses used for the various conditions are outlined here. 

PMID- 25049099
TI  - Photodynamic therapy for Barrett's oesophagus: How I do it.
AB  - Endoscopic photodynamic therapy (PDT) for Barrett's oesophagus with high-grade
      dysplasia or early carcinoma is undertaken after full investigation. Endoscopic
      assessment is mandatory to determine the extent of the Barrett's segment and
      neoplastic changes. Photofrin at 2mg/kgbw is used, followed 24-72h later by
      illumination of 630nm light, 200J/cm of lesion. The whole of the Barrett's
      segment should be exposed to illumination. Patients are followed up
      endoscopically at 3 months. 

PMID- 25049100
TI  - Endoscopic photodynamic therapy for oesophageal disease.
AB  - Photodynamic therapy is a very important technique for the eradication of
      widespread oesophageal mucosal disease which has the potential to degenerate to
      cancer. Patients unsuitable or unwilling to undergo radical therapy can be cured
      using photodynamic therapy. We predominantly treat patients with high-grade
      dysplasia in Barrett's oesophagus. Lesions that are visible macroscopically are
      removed using endoscopic mucosal resection. The remaining area is then treated in
      5cm segments at 3 monthly intervals with separate photosensitisation using
      endoscopic photodynamic therapy. 

PMID- 25049102
TI  - How to optimise topical photodynamic therapy in dermatology.

PMID- 25049101
TI  - Influence of non-irradiated and ultraviolet-A-irradiated N,N-dialanyl
      protoporphyrin and diarginine diprotoporphyrinate on the neutrophil respiratory
      burst in vitro.
AB  - N,N-Dialanyl protoporphyrin (PP(Ala)2) and diarginine diprotoporphyrinate
      (PP(Arg)2) are porphyrin photosensitizers that are currently being used in the
      photodynamic therapy (PDT) of cancer. In the present study, the effects of these
      agents on the neutrophil respiratory burst in vitro were investigated. In the
      case of non-stimulated neutrophils, the respiratory burst was significantly
      increased in the presence of PP(Ala)2 in concentration 5.0mg/l, while in the
      presence of PP(Arg)2 in the same concentration it did not change. By contrast,
      both photosensitizers decreased a respiratory burst by neutrophils stimulated
      with opsonized zymosan. Pre-irradiation of solutions of PP(Ala)2 and PP(Arg)2
      with ultraviolet A did not alter the observed responses. The prooxidative effect
      of PP(Ala)2 is probably due to the stimulation of protein kinase C, which plays a
      key role in the respiratory burst of non-stimulated cells, whereas the
      antioxidant effect of both photosensitizers may be explained by their inhibitory
      effect on EGFR tyrosine kinase, which plays an important role in the respiratory
      burst of cells stimulated by opsonized zymosan. The lack of effect of the two
      dyes after UV-A pre-irradiation may be due to rapid self-quenching of UV-A
      excited dye molecules to the ground state. The results of this study provide a
      starting point for experiments in animal models aimed at determining the clinical
      importance of the observed effects in cancer diagnosis and therapy. 

PMID- 25049103
TI  - Topical photodynamic therapy for non-cancerous skin conditions.
AB  - Topical photodynamic therapy (PDT) is a non-invasive therapeutic modality which
      is developing increasing use in dermatology. It is a well established treatment
      for pre-malignant and malignant skin tumours and over recent years there has also
      been encouraging evidence for its use in treating benign cutaneous disorders. We
      review the literature and clinical trials utilising topical PDT for non-cancerous
      skin conditions. Recalcitrant warts, acne vulgaris and psoriasis have so far been
      studied in most detail. At present, photosensitisers, light sources and treatment
      parameters of PDT vary in different clinical trials even for the same conditions.
      Optimum parameters for PDT need to be established and comparison randomised
      studies are required to clarify whether PDT for benign dermatoses is
      significantly superior to existing therapeutic modalities. 

PMID- 25049104
TI  - How we treat a superficial basal cell carcinoma with topical photodynamic therapy
      in Dundee.
AB  - Topical photodynamic therapy (PDT) is a highly effective treatment for
      superficial basal cell carcinoma (SBCC) (Morton CA, Brown SB, Collins S, et al.
      Guidelines for topical photodynamic therapy: report of a workshop of the British
      Photodermatology Group. Br J Dermatol 2004;146:552-67). Treatment is well
      tolerated, performed on an outpatient basis and can be repeated, and excellent
      outcomes and cosmetic results can be achieved. We have experience of over 3000
      topical PDT treatments for superficial non-melanoma skin cancer and dysplasia in
      the Photobiology Unit in Dundee and I will present our own experience of how to
      treat an SBCC with topical PDT in this article (Ibbotson SH, Moseley H,
      Brancaleon L, et al. Photodynamic therapy in dermatology: Dundee clinical and
      research experience. Photodiagn Photodyn Ther 2004;1:211-23). 

PMID- 25049105
TI  - Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) in dermatology: "How
      we do it".
AB  - In dermatology PDT has been proven to be effective in the treatment of actinic
      keratoses, basal cell carcinomas (BCC), Bowen's disease, superficial squamous
      cell carcinomas (SCC). 

PMID- 25049106
TI  - Photodynamic therapy in the management of a patient with Gorlin syndrome (naevoid
      basal cell carcinoma syndrome).
AB  - Gorlin syndrome (naevoid basal cell carcinoma syndrome) is a genetically linked
      disorder characterized by the development of multiple basal cell carcinomas
      (BCCs) throughout life. Cumulative surgery, cryotherapy and other conventional
      interventions can result in significant disfigurement by middle age. Radiotherapy
      is contra-indicated because the mutated gene underlying the syndrome, 'PTCH',
      increases sensitivity to ionising radiation, so there is significant likelihood
      of inducing further tumours in and around the irradiated area. Photodynamic
      therapy offers a non-invasive treatment option for patients with this condition,
      with the added advantage of causing minimal scarring. 

PMID- 25049107
TI  - "Geographical Distribution Patterns of Various Genes": genetic studies of human
      variation after 1945.
AB  - After WWII, physical anthropologists and human geneticists struggled hard to
      demonstrate distance from 'racial science' and 'eugenics'. This was a crucial
      factor in the 'revolution' of physical anthropology in the 1950s, as contemporary
      accounts referred to it. My paper examines the apparent turn during this period
      from anthropometric measurements to blood-group analysis, and from 'races' to
      'small endogamous populations', or 'isolates', as the unit of study. I
      demonstrate that anthropometry and blood-group analysis were used simultaneously
      and in the same research projects until the 1960s. Isolated populations were the
      new target groups of human population geneticists, from large continental groups
      to small village populations. Colonial infrastructures provided suitable
      conditions for these kinds of transnational research projects. I argue that this
      new framework helped to translate much of the content of earlier racial studies
      into a less attackable approach to human variation. 

PMID- 25049108
TI  - Propagation of cortical spreading depression into the hippocampus: The role of
      the entorhinal cortex.
AB  - Propagation of cortical spreading depression (CSD) to the subcortical structures
      could be the underlying mechanism of some neurological deficits in migraine with
      aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex
      and subcortical regions plays an important role in this propagation. In vitro
      combined neocortex-hippocampus brain slices were used to study the propagation
      pattern of CSD between the neocortex and the hippocampus. The effects of
      different compounds as well as tetanic electrical stimulations in the EC on
      propagation of CSD to the hippocampus were investigated. Repetitive induction of
      CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD
      entrance to the hippocampus via EC. Local application of AMPA receptor blocker
      CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the
      propagation of CSD to the hippocampus, whereas application of NMDA receptor
      blocker APV and GABAA receptor blocker bicuculline in this region reduced the
      probability of CSD penetration to the hippocampus. Application of tetanic
      stimulation in EC also facilitated the propagation of CSD entrance to the
      hippocampus. Our data suggest the importance of synaptic plasticity of EC in
      filtering the propagation of CSD into subcortical structures and possibly the
      occurrence of concomitant neurological deficits. Synapse 68:574-584, 2014. (c)
      2014 Wiley Periodicals, Inc.

PMID- 25049109
TI  - Dietary patterns and breast cancer: a case-control study in women.
AB  - PURPOSE: Since dietary habits have been associated with breast cancer, the tested
      research hypothesis was the associations between food patterns, as derived
      through multivariate methods, and breast cancer. METHODS: In a case-control
      study, Two-hundred and fifty consecutive, newly diagnosed breast cancer female
      patients (56 +/- 12 years) and 250 one-to-one age-matched, healthy controls were
      studied. A standardized, validated questionnaire assessing various socio
      demographic, clinical, lifestyle, and dietary characteristics was applied through
      face-to-face interviews. Factor analysis, with principal components method, was
      applied to extract dietary patterns from 86 foods or food groups consumption
      reported by the controls. RESULTS: Three components were derived explaining 43%
      of the total variation in consumption. Component 1 was characterized by the
      consumption of potatoes, red meat and its products, poultry and white meat, dairy
      products, use of margarine/butter in cooking or at the table, consumption of
      sausages, fried food as well as grilled meat or fish; component 2 was
      characterized by the consumption of whole grains, fruits, and vegetables; and
      component 3 was characterized by olive oil and fish consumption. After adjusting
      for various confounders, components 2 and 3 were favorably associated with the
      absence of having breast cancer [odds ratio (OR) 0.60, 95% CI 0.47-0.75 and OR
      0.81, 95% CI 0.66-0.99, respectively], while component 1 was not significantly
      associated with the disease. CONCLUSIONS: Adherence to healthy dietary patterns
      (including whole grains, fruits, and vegetables, olive oil, and fish) seems to be
      favorable in not having breast cancer, among middle-aged women.

PMID- 25049110
TI  - Higher intake of carotenoid is associated with a lower risk of colorectal cancer
      in Chinese adults: a case-control study.
AB  - PURPOSE: The associations between specific carotenoid intake and colorectal
      cancer risk remain inconsistent. The aim of this study was to examine the
      association between specific dietary carotenoid intake with colorectal cancer
      risk in Chinese adults. METHOD: From July 2010 to October 2013, 845 eligible
      colorectal cancer cases and 845 frequency-matched controls (age and sex)
      completed in-person interviews. A validated food frequency questionnaire was used
      to estimate dietary intake. Multivariate logistical regression models were used
      to calculate the odds ratio (OR) and 95% confidence intervals (95% CIs) of
      colorectal cancer risk after adjusting for various confounders. RESULTS: A strong
      inverse association was found between beta-cryptoxanthin intake and colorectal
      cancer risk. Compared with the lowest quartile, the highest quartile intake
      showed a risk reduction of 77% (OR 0.23, 95% CI 0.17-0.33, P trend < 0.01) after
      adjustment for various confounding variables. The inverse associations were also
      observed for alpha-carotene (OR 0.50, 95% CI 0.37-0.68, P trend < 0.01), beta
      carotene (OR 0.67, 95% CI 0.49-0.91, P trend < 0.01), and lycopene (OR 0.51, 95%
      CI 0.37-0.70, P trend < 0.01). There was no statistically significant association
      between lutein/zeaxanthin intake and colorectal cancer risk. These findings were
      consistent across cancer site, sources of controls, and smoking status. The
      inverse associations between dietary alpha-carotene, beta-cryptoxanthin, and
      lycopene intake and colorectal cancer risk were found in both males and females,
      while inverse associations between beta-carotene intake and colorectal cancer
      risk were only observed in males. CONCLUSIONS: Consumption of alpha-carotene,
      beta-carotene, beta-cryptoxanthin, and lycopene was inversely associated with
      colorectal cancer risk. No significant association was found between
      lutein/zeaxanthin intake and colorectal cancer risk.

PMID- 25049111
TI  - Feasibility of reirradiation in the treatment of locally recurrent rectal cancer.
AB  - BACKGROUND: Many patients with locally recurrent rectal cancer receive
      radiotherapy for the treatment of the primary tumour. It is unclear whether
      reirradiation is safe and effective when a local recurrence develops. The aim of
      this study was to evaluate the toxicity and oncological outcome of reirradiation
      in patients with locally recurrent rectal carcinoma. METHODS: From March 1994
      until December 2013, data on patients with locally recurrent rectal cancer
      (without distant metastasis) were entered into a database. Patients were
      reirradiated with a reduced dose of 30 Gy and received an intraoperative electron
      radiotherapy boost during surgery. Morbidity associated with radiotherapy,
      postoperative complications and oncological outcome were evaluated. RESULTS:
      Clear margins (R0) were obtained in 75 (55.6 per cent) of the 135 patients who
      were reirradiated. Forty-six patients developed serious postoperative
      complications and the 30-day mortality rate was 4.6 per cent. Multivariable
      analysis showed that margin status was the main factor influencing oncological
      outcome (hazard ratio for overall survival 2.51 for R1 and 3.19 for R2 versus R0
      resection; both P < 0.001). There was no significant difference in survival
      between the reirradiated group and a group of 113 patients who had full-course
      irradiation (5-year overall survival rate 34.1 and 39.1 per cent respectively; P
      = 0.278). Both reirradiation and full-course irradiation were associated with
      better survival than no irradiation in a historical control group of 24 patients
      (5-year overall survival rate 23 per cent; P = 0.225 and P = 0.062). CONCLUSION:
      Reirradiation (with concomitant chemotherapy) has few side-effects and
      complements radical resection of recurrent rectal cancer.

PMID- 25049112
TI  - Quantification of myocardial blood flow using (201)Tl SPECT and population-based
      input function.
AB  - OBJECTIVES: Thallium-201 ((201)Tl) single photon emission computed tomography
      (SPECT) is an important tool in the diagnosis of ischemic heart disease. Absolute
      quantification of myocardial blood flow (MBF) has the potential to provide more
      useful information on myocardial perfusion than semi-quantitative assessments.
      This study aimed to validate the quantification of MBF using (201)Tl cardiac
      SPECT based on a population-averaged input function (STD-IF) and one-point blood
      sample technique. METHODS: (201)Tl emission and computed tomography (CT)-based
      attenuation scans were performed on 11 healthy volunteers at rest using a
      SPECT/CT scanner. Individual input functions (IND-IFs) during the emission scans
      were based on arterial blood samples. The STD-IF technique was validated as
      follows: (1) optimal time to calibrate a STD-IF was determined to minimize
      differences between the calibrated STD-IF and the IND-IFs. (2) Tissue time
      activity curves (TTACs) were generated based on a single-tissue compartment model
      for MBFtrue = 0.5, 1.0, 1.5, and 2.0 mL/min/g, a constant distribution volume of
      45 mL/mL, and IND-IFs. The pseudo STD-IF for each subject was generated using the
      leave-one-out technique. Using the optimal calibration time and the pseudo STD
      IFs, MBF values were estimated on the TTACs with an autoradiography method.
      Optimal mid-scan time (MST) with a fixed duration of 20 min was determined to
      minimize intersubject variation in estimated MBF errors, and (3) Global and
      regional MBF values estimated with pseudo STD-IFs were compared to those with IND
      IFs using the optimal calibration time and MST. RESULTS: The optimal calibration
      time and MST were both 20 min after (201)Tl injection. Global MBF determined
      using both IND-IFs and pseudo STD-IF showed significant correlations with rate
      pressure products, R (2) = 0.645; p < 0.01 and R (2) = 0.303; p < 0.05,
      respectively. The mean percent error in regional MBF using pseudo STD-IFs was
      0.69 +/- 7.80 % (-12.80 to 14.25 %). No significant difference was observed
      between regional MBF values using IND-IFs and pseudo STD-IFs. CONCLUSION: This
      study demonstrated that the proposed technique based on a STD-IF and one-point
      blood sample provided hemodynamically reasonable global MBF values and the
      regional MBF values comparable to those with IND-IFs.

PMID- 25049113
TI  - Electronic structure of BSb defective monolayers and nanoribbons.
AB  - In this paper, we investigate two- and one-dimensional honeycomb structures of
      boron antimony (BSb) using a first-principles plane wave method within the
      density functional theory. BSb with a two-dimensional honeycomb structure is a
      semiconductor with a 0.336 eV band gap. The vacancy defects, such as B, Sb, B +
      Sb divacancy, and B + Sb antisite disorder affect the electronic and magnetic
      properties of the 2D BSb sheet. All the structures with vacancies have
      nonmagnetic metallic characters, while the system with antisite disorder has a
      semiconducting band structure. We also examine bare and hydrogen-passivated quasi
      one-dimensional armchair BSb nanoribbons. The effects of ribbon width (n) on an
      armchair BSb nanoribbon and hydrogen passivation on both B and Sb edge atoms are
      considered. The band gaps of bare and H passivated A-Nr-BSb oscillate with
      increasing ribbon width; this property is important for quantum dots. For ribbon
      width n = 12, the bare A-Nr-BSb is a nonmagnetic semiconductor with a 0.280 eV
      indirect band gap, but it becomes a nonmagnetic metal when B edge atoms are
      passivated with hydrogen. When Sb atoms are passivated with hydrogen, a
      ferromagnetic half-metallic ground state is observed with 2.09MUB magnetic
      moment. When both B and Sb edges are passivated with hydrogen, a direct gap
      semiconductor is obtained with 0.490 eV band gap with disappearance of the bands
      of edge atoms.

PMID- 25049115
TI  - Orders of magnitude extension of the effective dynamic range of TDC-based TOFMS
      data through maximum likelihood estimation.
AB  - In a recent article, we derived a probability distribution that was shown to
      closely approximate that of the data produced by liquid chromatography time-of
      flight mass spectrometry (LC/TOFMS) instruments employing time-to-digital
      converters (TDCs) as part of their detection system. The approach of formulating
      detailed and highly accurate mathematical models of LC/MS data via probability
      distributions that are parameterized by quantities of analytical interest does
      not appear to have been fully explored before. However, we believe it could lead
      to a statistically rigorous framework for addressing many of the data analytical
      problems that arise in LC/MS studies. In this article, we present new procedures
      for correcting for TDC saturation using such an approach and demonstrate that
      there is potential for significant improvements in the effective dynamic range of
      TDC-based mass spectrometers, which could make them much more competitive with
      the alternative analog-to-digital converters (ADCs). The degree of improvement
      depends on our ability to generate mass and chromatographic peaks that conform to
      known mathematical functions and our ability to accurately describe the state of
      the detector dead time-tasks that may be best addressed through engineering
      efforts. 

PMID- 25049114
TI  - Muscle strength, muscle mass, and physical disability in women with systemic
      lupus erythematosus.
AB  - OBJECTIVE: Data describing relationships between muscle strength, muscle mass,
      and physical disability among individuals with systemic lupus erythematosus (SLE)
      are limited. The present study examines the relationship of muscle strength and
      muscle mass with physical disability among adult women with SLE. METHODS: A total
      of 146 women from a longitudinal SLE cohort participated in the study. All
      measures were collected during an in-person research visit. Lower extremity
      muscle strength was assessed by peak knee torque of extension and flexion and by
      chair-stand time. Total lean body mass, appendicular lean mass, and fat mass
      (kg/m(2) ) were measured by whole-body dual x-ray absorptiometry. Self-reported
      physical disability was assessed using the Short Form 36 health survey (SF-36)
      physical functioning subscale, and the Valued Life Activities (VLA) disability
      scale. Spearman's rank correlation coefficients tested the correlations between
      muscle strength, muscle mass, and disability scores. Regression analyses modeled
      the effect of lower extremity muscle strength and mass on SF-36 and VLA
      disability scores controlling for age, SLE duration, SLE disease activity
      measured with the Systemic Lupus Activity Questionnaire, physical activity level,
      prednisone use, body composition, and depression. RESULTS: On all measures,
      reduced lower extremity muscle strength was associated with poorer SF-36 and VLA
      disability scores. Trends persisted after adjustment for covariates. Muscle mass
      was moderately correlated with muscle strength, but did not contribute
      significantly to adjusted regression models. CONCLUSION: Lower extremity muscle
      strength, but not muscle mass, was strongly associated with physical disability
      scores. While further studies are needed, these findings suggest that improving
      muscle strength may reduce physical disability among women with SLE.

PMID- 25049116
TI  - Thermal response of transparent silver nanowire/PEDOT:PSS film heaters.
AB  - Thermal response behavior of transparent silver nanowire/PEDOT:PSS film heaters
      are intensively studied for manipulating heating temperature, response time, and
      power consumption. Influences of substrate heat capacity, heat transfer
      coefficient between air and heater, sheet resistance and dimension of Ag nanowire
      film, on the thermal response are investigated from thermodynamic analysis.
      Suggestion is given for practical applications that if other parameters are
      fixed, Ag nanowire coverage can be utilized as an effective parameter to adjust
      the thermal response. The heat transfer coefficient plays opposite roles on
      thermal response speed and achievable steady temperature. A value of ~32 W m(-2)
      K(-1) is obtained from transient process analysis after correcting it by
      considering heater resistance variation during heating tests. Guidance of
      designing heaters with a given response time is provided by forming Ag nanowire
      film with a suitable sheet resistance on substrate of appropriate material and a
      certain thickness. Thermal response tests of designed Ag heaters are performed to
      show higher heating temperature, shorter response time, and lower power
      consumption (179  degrees C cm(2) W(-1)) than ITO/FTO heaters, as well as
      homogeneous temperature distribution and stability for repeated use. Potential
      applications of the Ag heaters in window defogging, sensing and thermochromism
      are manifested.

PMID- 25049117
TI  - CCSD-CTOCD static dipole shielding polarizability for quantification of the
      chiral NMR effects in oxaziridine derivatives.
AB  - Chiral discrimination by nuclear magnetic resonance (NMR) spectroscopy might be
      achieved through the pseudo-scalar derived from the dipole shielding
      polarizability tensor. Coupled Cluster Singles and Doubles-Quadratic Response
      (CCSD-QR) calculations inside the continuous translation of the origin of the
      current density formalism have been carried out to determine the effects of basis
      set, electron correlation, and gauge translation on the determination of this
      magnitude in oxaziridine derivatives. Inclusion of electronic correlation is
      needed for adequately describing the pseudo-scalar for the heavier nuclei, making
      CCSD a rigorous and affordable method to compute these high order properties in
      medium-sized molecules. The observable magnitudes for chiral discrimination
      (produced RF voltage and required electric field) are calculated. Half of the
      considered molecules show values of the observable magnitudes near the lower
      limit for experimental detection. Nuclei (19)F, (31)P, and (79)Br produce the
      largest values of RF voltage (50-80 nV). Moreover, (31)P and (79)Br are the
      nuclei requiring smallest electric fields (3 MVm(-1)) to separate the NMR
      signals, being then suitable for both the techniques.

PMID- 25049119
TI  - Beauty in a multicultural world.
AB  - The increased demand for facial cosmetic surgery has come from a more diverse,
      informed, and selective patient population from all walks of life. Virtually no
      two patients have the same background or cosmetic objectives. However, the
      classic tenets of beauty including phi, symmetry, averageness, youthfulness, and
      sexual dimorphism can be applied to persons of all ethnicities to assist in
      objectifying the abstract concept. 

PMID- 25049118
TI  - A nineteen gene-based risk score classifier predicts prognosis of colorectal
      cancer patients.
AB  - Colorectal cancer (CRC) patients frequently experience disease recurrence and
      distant metastasis. This study aimed to identify prognostic indicators, including
      individual responses to chemotherapy, in CRC patients. RNA-seq data was generated
      using 54 samples (normal colon, primary CRC, and liver metastases) from 18 CRC
      patients and genes associated with CRC aggressiveness were identified. A risk
      score based on these genes was developed and validated in four independent CRC
      patient cohorts (n = 1063). Diverse statistical methods were applied to validate
      the risk scoring system, including a generalized linear model likelihood ratio
      test, Kaplan-Meier curves, a log-rank test, and the Cox model. TREM1 and CTGF
      were identified as two activated regulators associated with CRC aggressiveness. A
      risk score based on 19 genes regulated by TREM1 or CTGF activation (TCA19) was a
      significant prognostic indicator. In multivariate and subset analyses based on
      pathological staging, TCA19 was an independent risk factor (HR = 1.894, 95% CI =
      1.227-2.809, P = 0.002). Subset stratification in stage III patients revealed
      that TCA19 had prognostic potential and identified patients who would benefit
      from adjuvant chemotherapy, regardless of age. The TCA19 predictor represents a
      novel diagnostic tool for identifying high-risk CRC patients and possibly
      predicting the response to adjuvant chemotherapy. 

PMID- 25049120
TI  - Facial aesthetic surgical goals in patients of different cultures.
AB  - The purpose of facial aesthetic surgery is to improve the patient's psychological
      well-being. To achieve this, the surgeon must understand the patient's body image
      and their aesthetic and psychological expectations. These factors must be judged
      in the context of their cultural background. The patient's cultural values must
      also be understood to optimize the doctor-patient relationship. 

PMID- 25049121
TI  - Rhinoplasty in the Middle Eastern nose.
AB  - In this article, the main characteristics of Middle Eastern patients seeking
      rhinoplasty are reported. Besides the preoperative preparation, surgical
      techniques that can be used to obtain good results are discussed. The pitfalls of
      profile alignment, tip procedures and skin have been noted as well. 

PMID- 25049122
TI  - Rhinoplasty in the Asian nose.
AB  - For Asian people with poorly developed dorsal height and tip height combined with
      thick skin, augmentation is the most common procedure in rhinoplasty. Nasal
      deformities are also prevalent. Frequent use of dorsal augmentation material and
      grafting procedures in Asian rhinoplasty results in a relatively high rate of
      revision surgery to correct complications. This article describes dorsal
      augmentation using alloplastic implant materials and several tip grafting
      procedures. Surgical techniques for the correction of a deviated nose and convex
      dorsum are also discussed, with emphasis on extracorporeal septoplasty as
      modified by the senior author. A technical guide is described to treat this
      condition. 

PMID- 25049123
TI  - African American rhinoplasty.
AB  - Rhinoplasty in patients of African descent requires a patient-specific approach,
      because the goals and ideal proportions differ from the white nose. This article
      discusses approaches to surgical correction of common anatomic variations. In
      addition, common pitfalls are outlined. 

PMID- 25049124
TI  - Rhinoplasty in the Mestizo nose.
AB  - Mestizo patients are the largest ethnic minority in the United States; the main
      facial plastic procedure they request is rhinoplasty. Mestizo noses are a
      challenge. It is common to find bulbous, undefined nasal tips sitting on a poorly
      structured osteocartilaginous framework. A structural approach is presented
      whereby support structures of the nose are strengthened and reinforced with
      structural grafts. A gradual approach to the nasal tip is presented whereby
      sutures and grafts are used to improve rotation and projection and create more
      definition. Cases showing long-term results are presented with discussion of the
      different surgical techniques used. 

PMID- 25049125
TI  - Asian blepharoplasty.
AB  - This article discusses in detail the cultural aesthetic issues that confront the
      surgeon interested in performing Asian blepharoplasty in terms of defining an
      aesthetic Asian ideal and the subject of natural and ethnic preservation of
      identity. The surgical methodology of how to perform a full-incision-based Asian
      blepharoplasty is outlined in a stepwise fashion along with the perioperative
      concerns (preoperative planning and counseling, nature of recovery, and
      complications and revision surgery). 

PMID- 25049126
TI  - Ethnic considerations in hair restoration surgery.
AB  - Patients of different ethnicities have specific characteristics that are
      essential for hair transplant surgeons to understand so that aesthetic results
      can be achieved. In this article, the approaches of follicular unit extraction
      and follicular unit grafting or strip hair transplants for pattern hair loss are
      reviewed, along with the procedures of eyebrow and beard transplants and surgical
      hairline advancement/forehead reduction surgeries, within various ethnic groups. 

PMID- 25049127
TI  - Laser skin treatment in non-Caucasian patients.
AB  - The demand for facial rejuvenation and cosmetic procedures is rising among all
      ethnicities and skin types. The authors present a review of lasers and how to
      select a laser based on skin type and the treatment goals of laser resurfacing:
      skin laxity, dyschromia, hair removal, keloid, and hypertrophic scarring. In
      addition, they discuss preprocedural and postprocedural considerations, potential
      complications, and their management to maximize patient outcomes and minimize
      risk. 

PMID- 25049128
TI  - Laser and face peel procedures in non-Caucasians.
AB  - Facial resurfacing procedures are becoming increasingly popular. The percentage
      of non-Caucasian individuals seeking these treatments continues to rise. Patients
      with darker skin types (Fitzpatrick skin types IV-VI) face unique challenges for
      successful facial skin resurfacing. Common issues encountered by non-Caucasian
      patients include dyschromias, acne scars, photoaging, keloid and hypertrophic
      scars, benign cutaneous tumors, and hair-related disorders. This article
      discusses the most frequently used lasers and chemical peels used to address
      these problems. 

PMID- 25049129
TI  - Scar treatment variations by skin type.
AB  - Patients and clinicians use skin color attributes such as color uniformity, color
      distribution, and texture to infer physiologic health status. Normalization of
      skin color, surface texture, and height are important treatment goals in the
      treatment of scars. Skin color, structure, and response to trauma, vary with
      ethnicity. The incidence of hypertrophic and keloid scar formation is influenced
      by these inherent skin attributes. Skin type influences the response to various
      modalities including laser therapy and surgical intervention, and skin
      differences must be considered in treatment planning to achieve optimal results. 

PMID- 25049131
TI  - Multicultural issues in facial plastic surgery.

PMID- 25049130
TI  - Considerations in non-Caucasian facial rejuvenation.
AB  - Aging of the face is inevitable and undeniable. This process includes a loss of
      skeletal support, soft tissue volume depletion, and a decrease in skin
      elasticity. The contribution of these 3 factors varies between individuals with
      noticeable hereditary influence. Characteristic ethnic features have been
      described in the literature, but as societies have changed, many of these ethnic
      variations have blended together. Facial cosmetic procedures must to be tailored
      to address these variations in anatomy, and consideration must be given to
      enhancing the facial skeleton, adequately lifting the soft tissues, and planning
      careful incisions to be closed under no tension. 

PMID- 25049132
TI  - Lactobacillus paracasei subsp paracasei L. casei W8 suppresses energy intake
      acutely.
AB  - BACKGROUND: Probiotic bacteria have been shown to have various effects on the
      microbiota; this may also affect appetite and may help promote weight loss and
      maintenance. OBJECTIVE: This study was conducted to investigate the effect of
      Lactobacillus paracasei subsp paracasei L. casei W8 (L. casei W8) on glucagon
      like peptide-1 (GLP-1) responses in an isolated pig intestine, in piglets and
      postprandially in humans. Additionally, the effect on subjective appetite, ad
      libitum energy intake, and glucose and insulin responses in humans was
      investigated. DESIGN: Piglets were fed with probiotics for 2 weeks and the effect
      on glucagon encoding gene (GCG) was investigated. An isolated pig intestine was
      perfused with L. casei W8 and the GLP-1 response was measured. Twenty-one
      subjects completed a randomized, controlled, crossover study with three arms.
      Each participant completed 3 test days testing the effect of low dose (LD) (10(9)
      CFU), high dose (HD) (10(10) CFU) L. casei W8 or placebo capsule. Subjective
      appetite was assessed before an ad libitum lunch was served. GLP-1, insulin and
      glucose concentrations were analyzed. RESULTS: Two weeks of treatment of piglets
      with L. casei W8 resulted in an increase in GCG expression compared to control
      animals (P<.05). L. casei W8 increased the GLP-1 response in the isolated pig
      intestine. In humans, L. casei W8 had an overall effect on energy intake
      (P=0.03), but no effects on subjective appetite sensation, overall glucose and
      insulin response and on GLP-1 release were observed (P>0.1). CONCLUSION: The
      probiotic bacteria L. casei W8 appears to lower food intake acutely, but the
      underlying mechanisms are not understood.

PMID- 25049133
TI  - Who gains? Genetic and neurophysiological correlates of BMI gain upon college
      entry in women.
AB  - The present investigation examined P3 event-related electroencephalographic
      potentials and a short and selected list of addiction-related candidate gene
      single nucleotide polymorphisms (SNPs) within 84 female students, aged 18-20 yrs.
      The students were assigned to groups defined by the presence versus absence of a
      positive body mass index (BMI) change from the pre-college physical exam to the
      current day. Analyses revealed significantly greater P3 latencies and reduced P3
      amplitudes during a response inhibition task among students who exhibited a BMI
      gain. BMI gain was also significantly associated with a ANKK1 SNP previously
      implicated in substance dependence risk. In logistic regression analyses, P3
      latencies at the frontal electrode and this ANKK1 genotype correctly classified
      71.1% of the students into the BMI groups. The present findings suggest that
      heritable indicators of impaired response inhibition can differentiate students
      who may be on a path toward an overweight or obese body mass.

PMID- 25049135
TI  - The effect of post-exercise drink macronutrient content on appetite and energy
      intake.
AB  - Carbohydrate and protein ingestion post-exercise are known to facilitate muscle
      glycogen resynthesis and protein synthesis, respectively, but the effects of post
      exercise nutrient intake on subsequent appetite are unknown. This study aimed to
      investigate whether protein induced satiety that has been reported at rest was
      still evident when pre-loads were consumed in a post-exercise context. Using a
      randomised, double blind, crossover design, 12 unrestrained healthy males
      completed 30 min of continuous cycling exercise at ~60% VO2peak, followed by
      five, 3 min intervals at ~85% VO2peak. Ten min post-exercise, subjects consumed
      500 ml of either a low energy placebo (15 kJ) (PLA); a 6% whey protein isolate
      drink (528 kJ) (PRO); or a 6% sucrose drink (528 kJ) (CHO). Sixty min after drink
      ingestion, a homogenous ad-libitum pasta lunch was provided and energy intake at
      this lunch was quantified. Subjective appetite ratings were measured at various
      stages of the protocol. Energy consumed at the ad-libitum lunch was lower after
      PRO (5831 +/- 960 kJ) than PLA (6406 +/- 492 kJ) (P<0.05), but not different
      between CHO (6111 +/- 901 kJ) and the other trials (P>0.315). Considering the
      post-exercise drink, total energy intake was not different between trials
      (P=0.383). There were no differences between trials for any of the subjective
      appetite ratings. The results demonstrate that where post-exercise liquid protein
      ingestion may enhance the adaptive response of skeletal muscle, this may be
      possible without affecting gross energy intake relative to consuming a low energy
      drink.

PMID- 25049134
TI  - Initial evidence that GLP-1 receptor blockade fails to suppress postprandial
      satiety or promote food intake in humans.
AB  - Glucagon-like peptide 1 (GLP-1) has incretin effects that are well-documented,
      but the independent role of GLP-1 action in human satiety perception is debated.
      We hypothesized that blockade of GLP-1 receptors would suppress postprandial
      satiety and increase voluntary food intake. After an overnight fast, eight normal
      weight participants (seven men, BMI 19-24.7 kg/m(2), age 19-29 year) were
      enrolled in a double-blind, placebo-controlled, randomized crossover study of the
      GLP-1 antagonist Exendin-[9-39] (Ex-9) to determine if the satiating effects of a
      meal are dependent on GLP-1 signaling in humans. Following a fasting blood draw,
      iv infusion of Ex-9 (600-750 pmol/kg/min) or saline began. Thirty minutes later,
      subjects consumed a standardized breakfast followed 90 min later (at the
      predicted time of maximal endogenous circulating GLP-1) by an ad libitum buffet
      meal to objectively measure satiety. Infusions ended once the buffet meal was
      complete. Visual analog scale ratings of hunger and fullness and serial
      assessments of plasma glucose, insulin, and GLP-1 concentrations were done
      throughout the experiment. Contrary to the hypothesis, during Ex-9 infusion
      subjects reported a greater decrease in hunger due to consumption of the
      breakfast (Ex-9 -62 +/- 5; placebo -41 +/- 9; P=0.01) than during placebo. There
      were no differences in ad libitum caloric intake between Ex-9 and placebo. Ex-9
      increased glucose, insulin, and endogenous GLP-1, which may have counteracted any
      effects of Ex-9 infusion to block satiety signaling. Blockade of GLP-1 receptors
      failed to suppress subjective satiety following a standardized meal or increase
      voluntary food intake in healthy, normal-weight subjects.

PMID- 25049136
TI  - Low maternal sensitivity at 6 months of age predicts higher BMI in 48 month old
      girls but not boys.
AB  - BACKGROUND: Large population-based studies suggest that systematic measures of
      maternal sensitivity predict later risk for overweight and obesity. More work is
      needed to establish the developmental timing and potential moderators of this
      association. The current study examined the association between maternal
      sensitivity at 6 months of age and BMI z score measures at 48 months of age, and
      whether sex moderated this association. DESIGN: Longitudinal Canadian cohort of
      children from birth (the MAVAN project). METHODS: This analysis was based on a
      dataset of 223 children (115 boys, 108 girls) who had structured assessments of
      maternal sensitivity at 6 months of age and 48-month BMI data available. Mother
      child interactions were videotaped and systematically scored using the Maternal
      Behaviour Q-Sort (MBQS)-25 items, a standardized measure of maternal sensitivity.
      Linear mixed-effects models and logistic regression examined whether MBQS scores
      at 6 months predicted BMI at 48 months, controlling for other covariates.
      RESULTS: After controlling for weight-relevant covariates, there was a
      significant sex by MBQS interaction (P=0.015) in predicting 48 month BMI z.
      Further analysis revealed a strong negative association between MBQS scores and
      BMI in girls (P=0.01) but not boys (P=0.72). Logistic regression confirmed that
      in girls only, low maternal sensitivity was associated with the higher BMI
      categories as defined by the WHO (i.e. "at risk for overweight" or above).
      CONCLUSIONS: A significant association between low maternal sensitivity at 6
      months of age and high body mass indices was found in girls but not boys at 48
      months of age. These data suggest for the first time that the link between low
      maternal sensitivity and early BMI z may differ between boys and girls.

PMID- 25049137
TI  - A brief intervention increases fruit and vegetable intake. A comparison of two
      intervention sequences.
AB  - BACKGROUND AND PURPOSE: To evaluate the effectiveness of two subsequent
      intervention components (motivational and self-regulatory components), placed in
      different order, to promote fruit and vegetable (FV) intake. METHODS: After
      baseline assessment, university students (N=205, aged 18-26 years) were allocated
      to two groups. One group received a motivational intervention (outcome
      expectancies, risk perception, and task self-efficacy) followed by a self
      regulatory intervention (planning and dietary self-efficacy) after 17 days. The
      second group received the same intervention conditions in the opposite order.
      Follow-up assessments were done after another 17 days. RESULTS: Both intervention
      sequences yielded gains in terms of FV intake and self-efficacy. However, this
      gain was only due to the self-regulatory component whereas the motivational
      component did not contribute to the changes. Moreover, changes in intention and
      self-efficacy mediated between intervention sequence and follow-up behavior,
      suggesting that improving these proximal predictors of FV intake was responsible
      for the behavioral gains. CONCLUSIONS: Findings highlight the superiority of a
      self-regulatory intervention over a motivational intervention when it comes to
      dietary changes in this sample of young adults. Moreover, changes in dietary self
      efficacy may drive nutritional changes.

PMID- 25049139
TI  - The influence of plate size on meal composition. Literature review and
      experiment.
AB  - Environmental factors, such as the size of containers, can influence our energy
      intake. Even though different sized food containers are often recommended to
      control portion sizes, the evidence to support this is contradictory. In the
      present study, we conducted a literature review and a controlled laboratory
      experiment to investigate whether plate size influences the composition of a meal
      and the total meal energy. The results of the review suggest that distraction
      factors, the type of container, the food-serving mode (self-service or being
      served) and the type of food offered all influenced the results observed in the
      various published studies. For the experiment in this study, eighty-three
      participants were individually invited to serve themselves a lunch from a buffet
      containing 55 replica food items. Either a standard size plate (27 cm) or a large
      plate (32 cm) was provided to the participants. The results of the experiment
      suggest that the plate size had no significant effect on the total energy of the
      meal (F(1,81) =0.782, P> .05). However, participants using a large plate served
      themselves significantly more vegetables (F(1,81) =4.786, P< .05), particularly
      vegetables generally eaten as side dishes (F(1,81) =6.804, P< .05). Therefore,
      reducing the plate size does not seem to be an appropriate intervention to reduce
      the total energy intake in order to promote weight loss. Rather, using a large
      plate might be a simple and inexpensive strategy to increase vegetable
      consumption.

PMID- 25049140
TI  - Sudden gains in behavioural activation for depression.
AB  - Sudden gains have been linked to improved outcomes in cognitive behaviour therapy
      for depression. The relationship between sudden gains and outcome is less clear
      in other treatment modalities, including interpersonal psychotherapy and
      supportive expressive therapy, which may indicate different mechanisms of change
      between treatment modalities. The current study examined sudden gains in adults
      meeting diagnostic criteria for depression (N = 40) offered up to 12 sessions of
      behavioural activation treatment. Sudden gains were found in 42.5% of the sample.
      Sudden gains occurred early (median pre-gain session 2) and were related to
      outcome: those who experienced a sudden gain had significantly lower post
      treatment scores on the PHQ-9. Furthermore, the proportion meeting the reliable
      and clinically significant change criteria at end of treatment was higher in the
      sudden gain group. These findings highlight the importance of understanding the
      mechanisms by which sudden gains relate to therapy outcome in behavioural
      activation.

PMID- 25049138
TI  - Perseveration augments the effects of cognitive restraint on ad libitum food
      intake in adults seeking weight loss.
AB  - As executive function may influence eating behaviors, our aim was to determine
      whether measures of executive function predict ad libitum food intake in subjects
      seeking weight loss. 78 obese, healthy individuals (40 female/38 male; age 36 +/-
      10 y; BMI 37.8 +/- 7.2 kg/m(2)) completed the Iowa Gambling Task to evaluate
      decision making, the Stroop Word Color Task to assess attention, the Wisconsin
      Card Sorting Task to measure perseveration, and the Three Factor Eating
      Questionnaire to measure disinhibition and cognitive restraint. Ad libitum energy
      intake over 3-days was then collected using a validated vending paradigm. When
      expressed as a percentage of an individual's weight maintaining energy needs
      (%WMEN), intake correlated positively with perseveration (r=0.24, p=0.03) and
      negatively with restraint (r=-0.51, p<0.0001). In a regression model of %WMEN
      (r(2)=0.59, p<0.0001), an interaction between perseveration and restraint was
      observed (p=0.05). Increased perseveration intensified the effect of restraint
      such that subjects with both high restraint and perseveration ate the least
      (median (IQR)=70 (62, 94) %WMEN), while those with low restraint and high
      perseveration ate the most (130 (102, 153) %WMEN). Subjects with low
      perseveration and high versus low restraint ate a median of 84 (70, 86) and 112
      (98, 133) %WMEN, respectively. The effects of perseveration on food intake are
      conditional on restraint, and may contribute to extremes of dietary intake in
      some individuals.

PMID- 25049141
TI  - Health, safety, and environmental risk assessment of steel production complex in
      central Iran using TOPSIS.
AB  - This research was carried out with the aim of presenting an environmental
      management plan for steel production complex (SPC) in central Iran. Following
      precise identification of the plant activities as well as the study area,
      possible sources of environmental pollution and adverse impacts on the air
      quality, water, soil, biological environment, socioeconomic and cultural
      environment, and health and safety of the employees were determined considering
      the work processes of the steel complex. Afterwards, noise, wastewater, and air
      pollution sources were measured. Subsequently, factors polluting the steel
      complex were identified by TOPSIS and then prioritized using Excel Software.
      Based on the obtained results, the operation of the furnaces in hot rolling
      process with the score 1, effluent derived from hot rolling process with the
      score 0.565, nonprincipal disposal and dumping of waste at the plant enclosure
      with the score 0.335, walking beam process with the score 1.483 respectively
      allocated themselves the highest priority in terms of air, water, soil and noise
      pollution. In terms of habitats, land cover and socioeconomic and cultural
      environment, closeness to the forest area and the existence of four groups of
      wildlife with the score 1.106 and proximity of villages and residential areas to
      the plant with the score 3.771 respectively enjoyed the highest priorities while
      impressibility and occupational accidents with the score 2.725 and cutting and
      welding operations with score 2.134 had the highest priority among health and
      safety criteria. Finally, strategies for the control of pollution sources were
      identified and Training, Monitoring and environmental management plan of the SPC
      was prepared. 

PMID- 25049142
TI  - Magnetic particulate matters in the ashes of few commonly used Indian cigarettes.
AB  - Physical aspects of tobacco samples, used in some commonly available Indian
      brands of cigarettes, with emphasis on their magnetic characterization before and
      after they get burnt into ashes, are described. The present work highlights the
      ultrafine nature of the cigarette ashes and provides a compositional insight of
      their constituent particulate matters as revealed by the XRD and SEM studies.
      Based on the EDX spectra, elemental distributions of different tobacco samples,
      before and after they get burnt, are presented. In this work, magnetic
      measurements of the un-burnt tobacco samples are reported. An attempt is made to
      shed light on the origin of magnetism observed in these samples. 

PMID- 25049143
TI  - Heredity of chronic bronchitis: a registry-based twin study.
AB  - BACKGROUND: Smoking is a major risk factor for lung diseases and lower
      respiratory symptoms, but since not all smokers develop chronic bronchitis and
      since chronic bronchitis is also diagnosed in never-smokers, it has been
      suggested that some individuals are more susceptible to develop chronic
      bronchitis due to genetics. OBJECTIVE: To study the relative influence of genetic
      and environmental factors on the variation in the susceptibility to chronic
      bronchitis. METHODS: In a population-based questionnaire study of 13,649 twins,
      50-71 years of age, from the Danish Twin Registry, we calculated sex-specific
      concordance rates and heritability of chronic bronchitis. The response rate was
      75%. RESULTS: The prevalence of chronic bronchitis was 9.3% among men and 8.5%
      among women. The concordance rate for chronic bronchitis was higher in
      monozygotic twins than in dizygotic twins among women; 0.30 vs. 0.17, but not
      among men; 0.15 vs. 0.18. The heritability of chronic bronchitis adjusted for
      smoking and age was 55% (36-71%) in women, whereas the susceptibility to chronic
      bronchitis in men for 25% (8-41%) was ascribable to familial environment but not
      to genetic factors. CONCLUSIONS: Chronic bronchitis shows a moderate familial
      aggregation, particularly in women. Increased susceptibility to respiratory
      disease among female smokers relative to male smokers may have a genetic origin.

PMID- 25049145
TI  - New tool for the study of hepatitis C virus genotype 3 and its associated liver
      disease biology.

PMID- 25049144
TI  - Structural associations of symptomatic knee osteoarthritis.
AB  - OBJECTIVE: Structural changes of osteoarthritis (OA) may occur in the absence of
      pain. In this study, we aimed to identify histopathologic features that are
      associated with symptomatic knee OA. METHODS: Medial tibial plateaus and synovium
      samples were obtained at the time of total knee replacement (TKR) surgery for OA
      (advanced OA group) or were obtained postmortem from subjects who had not sought
      medical attention for knee pain during the last year of life (non-OA control
      group). To identify features of OA, we compared the patients with advanced OA
      with the age-matched non-OA controls (n = 26 per group). To identify OA features
      associated with symptoms, we compared two additional groups of subjects who were
      matched for severity of chondropathy (n = 29 per group): patients undergoing TKR
      for symptomatic OA (symptomatic chondropathy group) and postmortem subjects with
      similar severity of chondropathy who were asymptomatic during the last year of
      life (asymptomatic chondropathy group). The histologic features of the samples
      were graded, and immunoreactivities for macrophages (CD68) and nerve growth
      factor (NGF) in the synovium were quantified. The cellular localization of
      synovial NGF was determined by double immunofluorescence analysis. RESULTS:
      Advanced OA cases displayed more severe changes in the synovium (synovitis,
      increased synovial NGF, and CD68-immunoreactive macrophages) and cartilage (loss
      of cartilage surface integrity, loss of proteoglycan, tidemark breaching, and
      alterations in chondrocyte morphology) than did the non-OA controls. Synovial NGF
      was localized predominantly to fibroblasts and to some macrophages. The
      symptomatic chondropathy group displayed greater levels of synovitis, synovial
      NGF, and loss of cartilage integrity, in addition to alterations in chondrocyte
      morphology, than did the asymptomatic chondropathy group (P < 0.05 for each
      comparison). CONCLUSION: Synovitis, increased synovial NGF, alterations in
      chondrocyte morphology, and loss of cartilage integrity are features of knee OA
      that may be associated with symptoms.

PMID- 25049146
TI  - Co-culture of bone marrow-derived mesenchymal stem cells overexpressing lipocalin
      2 with HK-2 and HEK293 cells protects the kidney cells against cisplatin-induced
      injury.
AB  - Conditioned medium of mesenchymal stem cells (MSCs) is now being used for its
      cytoprotective effects, especially when the cells are equipped with
      cytoprotective factors to strengthen them against unfavorable microenvironments.
      Overexpression of Lcn2 in MSCs mimics in vivo kidney injury. Hence, unraveling
      how Lcn2-engineered MSCs affect kidney cells has been investigated. Cisplatin
      treated HK-2 or HEK293 kidney cells were co-cultivated with Lcn2 overexpressing
      MSCs in upper and lower chambers of transwell plates. Proliferation, apoptosis,
      and expression of growth factors and cytokines were assessed in the kidney cells.
      Co-cultivation with the MSCs-Lcn2 not only inhibited cisplatin-induced
      cytotoxicity in the HK-2 and HEK293 cells, but increased proliferation rate,
      prevented cisplatin-induced apoptosis, and increased expression of growth factors
      and the amount of antioxidants in the kidney cells. Thus Lcn2-engineered MSCs can
      ameliorate and repair injured kidney cells in vitro, which strongly suggests
      there are beneficial effects of the MSCs-Lcn2 in cell therapy of kidney injury. 

PMID- 25049147
TI  - Photodynamic therapy of the intact breast.
AB  - As breast cancer is diagnosed in over a million patients a year it is a
      significant oncological issue. Treatment paradigms have shifted to emphasize
      breast preservation protocols. However, due to a lack of equipment and facilities
      this option is only rarely offered to poverty stricken patients and those in the
      developing world. Photodynamic therapy may play a role in allowing for greater
      breast conservation based in part on the emerging success of partial breast
      radiation. This paper will review the rationale behind and technical aspects for
      intact breast photodynamic therapy. 

PMID- 25049148
TI  - Photodynamic therapy of diseased bone.
AB  - OBJECTIVE: Photodynamic therapy (PDT) defines the light activation of a
      photosensitizing compound, leading to the generation of cytotoxic, reactive
      oxygen species. We are investigating the unique application of PDT for diseased
      bone. METHODS: Bioluminescent, human breast cancer cells (MT-1) were injected
      intracardially into athymic rats. At 2-3 weeks following injection rats developed
      diffuse bone metastases that were visible using an in vivo bioluminescence
      imaging system. Metastatic lesions within vertebrae and long bones were treated
      with differing regimens of 690nm laser light (25-150J) following injection of
      benzoporphyrin-derivative monoacid (BPD-MA) and the tumour response assayed
      histologically upon sacrifice. Subsequent large animal studies involved light
      propagation studies in porcine vertebrae and BPD-MA-PDT treatment of large
      primary osteosarcomas in canine. Canine were subject to high dose PDT (500J/cm).
      A second rat model involved bacterial infection in bone. Bioluminescent
      Staphylococcus aureus (S. aureus) were grown as biofilms onto wires, implanted
      into rat tibia and exposed to 5-aminolevulinic acid (ALA)-PDT delivered
      percutaneously with 635nm laser light (75J/cm(2)). Response to therapy was
      monitored as changes in bioluminescence signal and colony forming assay upon
      sacrifice. RESULTS: PDT (150J) proved effective in ablating metastatic lesions
      within rat femur and lumbar vertebrae. Porcine studies confirmed the average
      depth of light penetration into trabecular bone as 0.16+/-0.04cm with an average
      incident fluence rate of 4.3mW/cm(2), however, the necrotic/non-necrotic
      interface extended 0.6cm out from the treatment fiber. In canine a single, high
      dose treatment created well-circumscribed margins of effect encompassing the
      entire 3-4cm osteosracoma. Finally, ALA-PDT proved effective against S. aureus
      biofilms in bone, although recurrent infection did occur in some. CONCLUSIONS:
      Results support the application of PDT to the treatment of primary or metastatic
      lesions within bone. Secondly, ALA-PDT may be useful as a treatment for
      osteomyelitis with repeat or chronic treatment regimens.

PMID- 25049149
TI  - Initial experience of the use of photodynamic therapy (PDT) in recurrent
      malignant and pre-malignant lesions of the vulva.
AB  - OBJECTIVES: To assess the suitability and effectiveness of photodynamic therapy
      (PDT) in the treatment and symptom relief of vulval intraepithelial neoplasia
      (VIN), other pre-malignant and early neoplastic conditions of the vulva in an out
      patient setting. METHODS: Patients were selected from the vulvoscopy clinic
      whilst being investigated or under long-term follow-up. PDT was offered to
      patients in whom other treatments had failed or were unsuitable. 5-Aminoleuvinic
      acid (5-ALA) was used as a topical pro-drug, inducing the photosensitiser
      protoporphyrin IX. This was applied 4-6h before treatment. Laser light (630nm)
      generated by a Diode laser and Light Emitting Diode (LED) non-laser light of
      630nm wavelength was also used. Initially, PDT was carried out with no analgesia,
      followed by oral analgesia, inhaled nitrous oxide and oral anxiolytic. Patients
      were seen and examined 2-3 weeks following treatment to assess clinical and
      symptomatic improvement. Further review was arranged as required. RESULTS: All
      those who had been symptomatic described improvement of their symptoms and all
      improved clinically. However, pain was a significant side effect during treatment
      and for 24h post treatment in most cases. CONCLUSION: The use of PDT for pre
      malignant and early malignant vulval conditions, particularly VIN appears to be
      effective in the control of symptoms and can be carried out in an outpatient
      setting. However, a further long-term study, combined with biopsy, is needed to
      assess the pathological response. Pain is a significant side effect.

PMID- 25049150
TI  - Potential of cationic porphyrins for photodynamic treatment of cutaneous
      Leishmaniasis.
AB  - Four tetracationic porphyrins have been investigated for their ability to photo
      inactivate Leishmania major promastigotes. Parallel photocytotoxicity assays
      against keratinocytes and macrophages show significant differences in activity
      between the microorganism and mammalian cells. Results suggest that it may be
      possible to photodynamically inactivate macrophages infected with Leishmania and
      the promastigote form of the microorganism, while minimising damage to
      surrounding tissue. 

PMID- 25049151
TI  - Autofluorescence and Photofrin-induced fluorescence imaging and spectroscopy in
      an animal model of oral cancer.
AB  - Developments in the fluorescence detection of cancer aim either to distinguish
      tissue autofluorescence from that of injected fluorophores or to exploit
      differences in autofluorescent spectra of normal versus transforming,
      premalignant and malignant tissue. This study evaluates the utility of
      autofluorescence and Photofrin-induced fluorescence imaging and spectroscopy to
      distinguish tissue transformation associated with early malignant change in the
      oral cavity. The model of tissue transformation used was that induced by the
      carcinogen DMBA in the hamster buccal cheek pouch. Fluorescence spectra were
      obtained using a high-sensitivity fiber optic spectrometer, while imaging was
      performed using a Multispectral Fluorescence Guidance (MFG) system designed for
      use in intraoperative fluorescence imaging during photodynamic therapy. The
      results demonstrate that Photofrin fluorescence can be used to predict the
      pathologic state of tissue, the fluorescence intensity being directly
      proportional to the degree of malignant transformation. Autofluorescence
      detection measured two parameters that are altered by transformation stage: the
      red/green fluorescence ratio and the total fluorescence intensity. The most
      striking feature was the change in the latter in malignant tissue. The MFG
      imaging device performed as well as spectroscopy: the sensitivity and specificity
      for the imaging system were 65% and 90% for autofluorescence and 87% and 85% with
      Photofrin. This indicates that either the autofluorescence intensity index of the
      tissue or the Photofrin-induced fluorescence may provide a good parameter for the
      "first approximation" characterization of the tissue. 

PMID- 25049152
TI  - Fab fragment labeled with ICG-derivative for detecting digestive tract cancer.
AB  - BACKGROUND: In previous studies, we generated infrared ray fluorescence-labeled
      monoclonal antibodies and developed an infrared ray fluorescence endoscope
      capable of detecting the monoclonal antibodies to establish a novel diagnostic
      technique for gastrointestinal cancer. Although the whole IgG molecule has
      commonly been used for preparation of labeled antibodies, labeled IgG displays
      insufficient sensitivity and specificity, probably resulting from non-specific
      binding of the Fc fragment to target cells or interference between fluorochromes
      on the identical labeled antibody, which might be caused by molecular structure.
      In this in vitro study, we characterized an Fc-free fluorescence-labeled Fab
      fragment, which was expected to yield more specific binding to target cells than
      the whole IgG molecule. METHODS: An anti-mucin antibody and ICG-ATT, an ICG
      derivative, were used as the labeled antibody and labeling compound,
      respectively. Paraffin sections of excised gastric cancer tissues were subjected
      to staining. The labeled whole IgG molecule (ICG-ATT-labeled IgG) and the labeled
      Fab fragment (ICG-ATT-labeled Fab) were prepared according to a previous report,
      and the fluorescence properties, antibody activities, and features of
      fluorescence microscope images obtained from paraffin sections were compared.
      RESULTS: Both ICG-ATT-labeled Fab and ICG-ATT-labeled IgG were excited by a near
      infrared ray of 766nm, and maximum emission occurred at 804nm. Antibody
      activities of ICG-ATT-labeled Fab were shown to be similar to those of unlabeled
      anti-MUC1 antibody. The fluorescence intensity obtained from paraffin sections of
      excised gastric cancer tissues revealed a tendency to be greater with ICG-ATT
      labeled Fab than with ICG-ATT-labeled IgG. CONCLUSIONS: The infrared ray
      fluorescence-labeled Fab fragment was likely to be more specific than the
      conventionally labeled antibodies. Fragmentation of antibodies is considered to
      contribute to improved sensitivity and specificity of labeled antibodies for
      detection of micro gastrointestinal cancers.

PMID- 25049153
TI  - Biophotonics and immune responses-Highlights from a new SPIE photonics west
      conference (BIOS 2006).
AB  - This report summarizes some highlights from the "Biophotonics and Immune
      Responses", a new 2006 SPIE Photonics West Biomedical Optics (BIOS 2006)
      Conference. Some exciting recent progresses in host immune responses elicited by
      photodynamic therapy and other novel phototherapies are discussed. 

PMID- 25049154
TI  - Influence of formulation factors on methyl-ALA-induced protoporphyrin IX
      accumulation in vivo.
AB  - Photodynamic therapy (PDT) is a medical treatment by which a combination of a
      photosensitising drug and visible light cause the destruction of selected cells.
      Thick lesions, such as nodular basal cell carcinomas (BCCs), or lesions with
      overlying keratinous debris, are reported as being difficult to eradicate using 5
      aminolevulinic acid-based photodynamic therapy (ALA-PDT). Such treatment failures
      have been attributed to the shallow penetration of water-soluble drugs like ALA.
      In addition, the current scarcity of sophisticated drug delivery research
      centered on PDT applications has meant that accurate comparison of similar
      clinical studies is difficult. This paper investigates, for the first time, novel
      drug delivery systems for controlled drug delivery of methyl-ALA (M-ALA).
      Pressure sensitive adhesive (PSA) and bioadhesive patches containing defined M
      ALA loadings and a standard cream containing equivalent amounts of drug were
      applied to the skin of mice for defined periods of time and the fluorescence of
      the protoporphyrin IX (PpIX) induced measured over 24h. Of major importance, the
      PSA patches containing low drug loadings induced high PpIX levels, which were
      limited to the site of application, after only 1h applications. Such systems have
      the potential to improve selectivity of PpIX accumulation, increase simplicity of
      treatment and, due to the low drug loadings required, reduce costs of clinical
      PDT. PSA patches would be most suitable for application to areas of dry skin,
      while bioadhesive patches would be suitable for moist areas, such as the mouth or
      lower female reproductive tract and have been shown here to induce significant
      PpIX production at the site of application after 4h applications of patches
      containing high drug loadings. 

PMID- 25049155
TI  - Joint British Medical Laser Association and Yorkshire Laser Centre:
      Photodetection and photodynamic therapy meeting.

PMID- 25049156
TI  - Mini-symposium on Photodynamic Medicine: On the way to success Organised by
      Research Division of Gynaecology, Department of Obstetrics & Gynaecology,
      University Hospital, Zurich (Head: Professor Heinrich Walt, PhD).

PMID- 25049157
TI  - New oral anticoagulants for non-valvular atrial fibrillation: harder to handle
      than expected.

PMID- 25049158
TI  - Organocatalytic cascade reactions: towards the diversification of
      hydroisochromenes and chromenes through two different activation modes.
AB  - The organocatalytic enantioselective syntheses of functionalized
      hydroisochromenes and chromenes by trienamine-mediated [4+2]
      cycloaddition/nucleophilic ring-closing and iminium-ion/aminal-mediated oxa
      Michael/Michael/nucleophilic ring-closing with 2-nitroallylic alcohols are
      presented. The corresponding cycloadducts, with up to five stereocenters, are
      formed in good yield and excellent enantioselectivities. The synthetic
      applications of the obtained products have been demonstrated. 

PMID- 25049159
TI  - [Anti-NMDAR (N-methy-D-aspartate receptor) limbic encephalitis diagnosed by 18F
      FDG PET/CT].

PMID- 25049160
TI  - [Mesothelioma staging with 18F-FDG PET/CT. A case report with simultaneous
      pleural and peritoneal infiltration].

PMID- 25049161
TI  - Mobility and subsistence at the Willandra Lakes: a comparative analysis of
      femoral cross-sectional properties in the Lake Mungo 3 skeleton.

PMID- 25049162
TI  - High-performance polymers from nature: catalytic routes and processes for
      industry.
AB  - It is difficult to imagine life today without polymers. However, most chemicals
      are almost exclusively synthesized from petroleum. With diminishing oil reserves,
      establishing an industrial process to transform renewables into high-value
      chemicals may be more challenging than running a car without gasoline. This is
      due to the difficulty in setting up processes that are novel, profitable, and
      environmentally benign at the same time. Additionally, the quest for
      sustainability of renewable resources should be based on incorporating ethical
      considerations in the development of plans that utilize feedstocks intended for
      human nutrition and health. Thus, it is important to use bio-energy containing
      renewable resources in the most efficient way. This Concept goes beyond the
      synthesis of monomers and provides insights for establishing an industrial
      process that transforms renewable resources into high-value chemicals, and it
      describes careful investigations that are of paramount importance, including
      evaluations from an economical and an ecological perspective. The synthesis of
      monomers suitable for polymer production from renewable resources would ideally
      be accompanied by a reduction in CO2 emission and waste, through the complete
      molecular utilization of the feedstock. This Concept advocates the drop-in
      strategy, and is guided by the example of catalytically synthesized dimethyl 1,19
      nonadecanedioate and its alpha,omega-functionalized derivatives. With respect to
      the Twelve Principles of Green Chemistry, this Concept describes a technological
      leap forward for a sustainable green chemical industry. 

PMID- 25049163
TI  - Differential response of Arabidopsis leaves and roots to cadmium: glutathione
      related chelating capacity vs antioxidant capacity.
AB  - This study aims to uncover the spatiotemporal involvement of glutathione (GSH) in
      two major mechanisms of cadmium (Cd)-induced detoxification (i.e. chelation and
      antioxidative defence). A kinetic study was conducted on hydroponically grown
      Arabidopsis thaliana (L. Heyhn) to gain insight into the early events after
      exposure to Cd. Cadmium detoxification was investigated at different levels,
      including gene transcripts, enzyme activities and metabolite content. Data
      indicate a time-dependent response both within roots and between plant organs.
      Early on in roots, GSH was preferentially allocated to phytochelatin (PC)
      synthesis destined for Cd chelation. This led to decreased GSH levels, without
      alternative pathways activated to complement GSH's antioxidative functions. After
      one day however, multiple antioxidative pathways increased including superoxide
      dismutase (SOD), ascorbate (AsA) and catalase (CAT) to ensure efficient
      neutralization of Cd-induced reactive oxygen species (ROS). As a consequence of
      Cd retention and detoxification in roots, a delayed response occurred in leaves.
      Together with high leaf thiol contents and possibly signalling responses from the
      roots, the leaves were protected, allowing them sufficient time to activate their
      defence mechanisms. 

PMID- 25049164
TI  - Patients who feel judged about their weight have lower trust in their primary
      care providers.
AB  - OBJECTIVE: To evaluate whether overweight and obese patients have less trust in
      their primary care providers (PCPs) if they feel judged about their weight by
      these PCPs. METHODS: We conducted a national internet-based survey of 600 adults
      engaged in primary care with a BMI >= 25 kg/m(2) in 2012. Our dependent variable
      was high patient trust in their PCP (score >= 8/10). Our independent variable was
      "feeling judged about my weight by my PCP" dichotomized as "often/sometimes"
      versus "never." We conducted a multivariate logistic regression model adjusted
      for patient and PCP factors using survey weights. RESULTS: Overall, 21% felt that
      their PCP judged them about their weight. Respondents who perceived judgment were
      significantly less likely to report high trust in their PCP [OR 0.55, 95% CI 0.31
      0.98]. CONCLUSION: While only a fifth of overweight and obese patients perceived
      weight-related judgment from their PCPs, these patients were significantly less
      likely to report high trust in these providers. Given patients' decreased trust
      in providers who convey weight-related judgment, our results raise concerns about
      potential effects on the doctor-patient relationship and patient outcomes.
      PRACTICE IMPLICATIONS: Addressing provider stigma toward patients with obesity
      could help build trust in these patient-provider relationships and improve
      quality of care.

PMID- 25049165
TI  - Screening of bacterial biocontrols against sapstain fungus (Lasiodiplodia
      theobromae Pat.) of rubberwood (Hevea brasiliensis Muell.Arg.).
AB  - Diverse bacterial biocontrol agents from various sources of aerobic composts
      against the sapstain fungus Lasiodiplodia theobromae in rubberwood (Hevea
      brasiliensis) were isolated, screened and identified by various morphological,
      biochemical and molecular techniques. The inhibitory effect of seventeen
      bacterial isolates was examined and seven exhibited inhibition towards the
      sapstain fungus. Among the seven antagonists, six were conclusively identified as
      Bacillus subtilis and one as Paenibacillus polymyxa using 16S rRNA-encoding gene
      sequencing. This is the first report on the occurrence of P. polymyxa, a potent
      biofertilizer and antagonist in vermicompost. HiCrome Bacillus agar was
      identified as an effective medium for differentiation of B. subtilis from other
      Bacillus species. The present work demonstrates the efficacy of the antagonistic
      property of B. subtilis strains against rubberwood sapstain fungus. Culture-based
      antagonistic inhibition displayed by B. subtilis can be extended to cater to the
      biocontrol requirements of wood-based industries against the stain fungus. The
      study showed the utility of an integrated approach, employing morphological,
      biochemical and molecular tools for conclusive identification of several
      bacterial isolates present in aerobic composts from diverse sources. 

PMID- 25049166
TI  - Supplement 2008-2010 (no. 48) to the White-Kauffmann-Le Minor scheme.
AB  - This supplement (no. 48) of the White-Kauffmann-Le Minor scheme reports on the
      characterization of 63 new Salmonella serovars and 25 new variants of previously
      described Salmonella serovars recognized by the WHO Collaborating Centre for
      Reference and Research on Salmonella between 2008 and 2010. Forty-four new
      serovars were assigned to Salmonella enterica subspecies enterica, 12 to
      subspecies salamae, two to subspecies arizonae, two to subspecies diarizonae and
      three to subspecies houtenae. All these new serovars or new variants are
      described with their multilocus sequence type. 

PMID- 25049167
TI  - Gluconic acid produced by Gluconacetobacter diazotrophicus Pal5 possesses
      antimicrobial properties.
AB  - Gluconic acid is produced in large quantities by the endophytic and diazotrophic
      bacterium Gluconacetobacter diazotrophicus Pal5. This organic acid derives from
      direct oxidation of glucose by a pyrroloquinoline-quinone-linked glucose
      dehydrogenase in this plant growth-promoting bacterium. In the present article,
      evidence is presented showing that gluconic acid is also responsible for the
      antimicrobial activity of G. diazotrophicus Pal5. The broad antagonistic spectrum
      includes Gram-positive and -negative bacteria. Eukaryotic microorganisms are more
      resistant to growth inhibition by this acid. Inhibition by gluconic acid can be
      modified through the presence of other organic acids. In contrast to other
      microorganisms, the Quorum Sensing system of G. diazotrophicus Pal5, a regulatory
      mechanism that plays a key role in several microbe-microbe interactions, is not
      related to gluconic acid production and the concomitant antagonistic activity. 

PMID- 25049168
TI  - Thymol disrupts the membrane integrity of Salmonella ser. typhimurium in vitro
      and recovers infected macrophages from oxidative stress in an ex vivo model.
AB  - Salmonella is a common bacterial enteropathogen responsible for many deaths every
      year. In the present study, we evaluated the mechanism of action of thymol
      against Salmonella ser. typhimurium, as well as its potential to induce
      intracellular killing and recovery from oxidative stress in macrophages. The
      minimum inhibitory concentration (MIC) of thymol against S. typhimurium was found
      to be 750 mg/l, and the CFU count decreased in a time-dependent manner. Excessive
      release of cellular materials and potassium ion also occurred in a time-dependent
      manner. Scanning electron microscopy showed disruption of membrane integrity.
      Intracellular killing capacity of macrophages was enhanced upon thymol treatment
      compared to control untreated cells. Thymol significantly reduced production of
      nitric oxide in a time-dependent manner, as well as the glutathione level.
      Disruption of membrane integrity was confirmed as the principle mechanism of
      action of thymol against S. typhimurium. Further, its potent role in inducing
      intracellular killing of S. typhimurium and recovery from oxidative stress in
      macrophages suggests that thymol can be applied as a naturally occurring drug
      against S. typhimurium in place of synthetic drugs. 

PMID- 25049169
TI  - Global transcriptomic analysis uncovers a switch to anaerobic metabolism in
      tellurite-exposed Escherichia coli.
AB  - Tellurite (TeO3(2-)) is harmful for most microorganisms, especially Gram-negative
      bacteria. Even though tellurite toxicity involves a number of individual aspects,
      including oxidative stress, malfunctioning of metabolic enzymes and a drop in the
      reduced thiol pool, among others, the general mechanism of toxicity is rather
      complex and not completely understood to date. This work focused on DNA
      microarray analysis to evaluate the Escherichia coli global transcriptomic
      response when exposed to the toxicant. Confirming previous results, the induction
      of the oxidative stress response regulator soxS was observed. Upregulation of a
      number of genes involved in the global stress response, protein folding, redox
      processes and cell wall organization was also detected. In addition,
      downregulation of aerobic respiration-related genes suggested a metabolic switch
      to anaerobic respiration. The expression results were validated through oxygen
      consumption experiments, which corroborated that tellurite-exposed cells
      effectively consume oxygen at lower rates than untreated controls. 

PMID- 25049170
TI  - Spectroscopic properties of transparent Er-doped oxyfluoride glass-ceramics with
      GdF3.
AB  - Optically active glass-ceramics (GC) with the low-phonon phases of fluorides,
      doped with Er(3+) was studied. Glass based on SiO2-Al2O3-Na2F2-Na2O-GdF3-BaO
      system was obtained. Dopant were introduced to the glass in an amount of 0.01 mol
      Er2O3 per 1 mol of glass. DTA/DSC study shows multi-stage crystallization. XRD
      identification of obtained phases did not confirm the presence of pure GdF3
      phase. Instead of that ceramization process led to formation of NaGdF4 and
      BaGdF5. The structural changes were studied using FT-IR spectroscopic method. The
      study of luminescence of the samples confirmed that optical properties of the
      obtained GC depend on crystallizing phases during ceramization. Time resolved
      spectroscopy of Er-doped glass showed the 3 and 8 times increase of lifetime of
      emission from (4)S3/2 and (4)F9/2 states, respectively. It confirms the erbium
      ions have ability to locate in the low phonon gadolinium-based crystallites. The
      results give possibility to obtain a new material for optoelectronic application.

PMID- 25049171
TI  - The effect of SiO2/Al2O3 ratio on the structure and microstructure of the glazes
      from SiO2-Al2O3-CaO-MgO-Na2O-K2O system.
AB  - Ceramic glazes are commonly used to covering of the facing surface of ceramics
      ware. A well-chosen oxide composition and firing conditions of glazes causes
      significant improvement of technical parameters of ceramic products. Modern
      glazes are classified as glass-ceramic composites with different crystalline
      phases arising during firing. The presence of crystals in the glass matrix is
      influenced by many factors, especially by oxides molar composition. A crucial
      role is played by the molar ratio of SiO2/Al2O3. In this work the six composition
      of glazes from SiO2-Al2O3-CaO-MgO-Na2O-K2O system were examined. The only
      variable is the ratio of the silicon oxideto alumina at a constant content of
      other components: MgO, CaO, K2O, Na2O, ZnO. In order to determine the real phase
      composition of the obtained glazes research on fluorescence spectrometer (XRF)
      were done. For structural studies X-ray diffraction (XRD) and spectroscopic in
      the middle infrared (MIR) were performed. In order to determine the state of the
      surface (microstructure) research on the scanning electron microscope (SEM) with
      EDX. The research allowed to determine the influence of SiO2/Al2O3 ratio on the
      structure and phase composition of glazes and the nature, and type of formed
      crystalline phases.

PMID- 25049172
TI  - Structural and optical study on antimony-silicate glasses doped with thulium
      ions.
AB  - Structural, spectroscopic and thermal properties of SiO2-Al2O3-Sb2O3-Na2O glass
      system doped with 0.2 mol% Tm2O3 have been presented. Synthesis of antimony
      silicate glasses with relatively low phonon energy (600 cm(-1), which implicates
      a small non-radiative decay rate) was performed by conventional high-temperature
      melt-quenching methods. The effect of SiO2/Sb2O3 ratio in fabricated Tm(3+) doped
      glass on thermal, structural and luminescence properties was investigated. On the
      basis of structural investigations decomposition of absorption bands in the
      infrared FTIR region was performed, thus determining that antimony ions are the
      only glass-forming ions, setting up the lattice of fabricated glasses.
      Luminescence band at the wavelength of 1.8 MUm corresponding to (3)F4->(3)H6
      transition in thulium ions was obtained under 795 nm laser pumping. It was
      observed that combination of relatively low phonon energy and greater separation
      of optically active centers in the fabricated glasses influenced in decreasing
      the luminescence intensity at 1800 nm.

PMID- 25049173
TI  - Propentophylline increases striatal dopamine release but dampens methamphetamine
      induced dopamine dynamics: A microdialysis study.
AB  - While there are currently no medications approved for methamphetamine (METH)
      addiction, it has been shown that propentofylline (PPF), an atypical
      methylxanthine, can suppress the rewarding effects of methamphetamine (METH) in
      mice. This experiment studied the interactions of PPF with METH in striatal
      dopaminergic transmission. Herein, the impact of PPF (10-40mM, intrastriatally
      perfused (80min) on the effect of METH (5mg/kg, i.p.) on striatal dopamine (DA)
      release was evaluated using brain microdialysis in Sprague-Dawley adult rats.
      METH was injected at the 60min time point of the 80min PPF perfusion. The
      extracellular levels of DA and its metabolites 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA) were determined using high performance liquid
      chromatography with electrochemical detection (HPLC-ED). PPF induced a
      concentration-dependent increase in DA release beginning 30min after the onset of
      PPF perfusion. DA peak levels evoked by 40mM PPF were similar to those induced by
      5mg/kg METH i.p. Only the highest concentration of PPF decreased the METH-induced
      DA peak (circa 70%). The significant decreases in extracellular levels of DOPAC
      and HVA evoked by METH were partially blocked by 10 and 20mM PPF. Although 40mM
      of PPF also partially blocked the METH-induced DOPAC decrease, it completely
      blocked HVA depletion after a transient increase in HVA levels in METH-treated
      rats. Data indicates for the first time that while PPF increases presynaptic
      striatal DA dynamics it attenuates METH-induced striatal DA release and
      metabolism. 

PMID- 25049174
TI  - High resolution 1H NMR-based metabonomic study of the auditory cortex analogue of
      developing chick (Gallus gallus domesticus) following prenatal chronic loud music
      and noise exposure.
AB  - Proper functional development of the auditory cortex (ACx) critically depends on
      early relevant sensory experiences. Exposure to high intensity noise
      (industrial/traffic) and music, a current public health concern, may disrupt the
      proper development of the ACx and associated behavior. The biochemical mechanisms
      associated with such activity dependent changes during development are poorly
      understood. Here we report the effects of prenatal chronic (last 10 days of
      incubation), 110dB sound pressure level (SPL) music and noise exposure on
      metabolic profile of the auditory cortex analogue/field L (AuL) in domestic
      chicks. Perchloric acid extracts of AuL of post hatch day 1 chicks from control,
      music and noise groups were subjected to high resolution (700MHz) (1)H NMR
      spectroscopy. Multivariate regression analysis of the concentration data of 18
      metabolites revealed a significant class separation between control and loud
      sound exposed groups, indicating a metabolic perturbation. Comparison of absolute
      concentration of metabolites showed that overstimulation with loud sound,
      independent of spectral characteristics (music or noise) led to extensive usage
      of major energy metabolites, e.g., glucose, beta-hydroxybutyrate and ATP. On the
      other hand, high glutamine levels and sustained levels of neuromodulators and
      alternate energy sources, e.g., creatine, ascorbate and lactate indicated a
      systems restorative measure in a condition of neuronal hyperactivity. At the same
      time, decreased aspartate and taurine levels in the noise group suggested a
      differential impact of prenatal chronic loud noise over music exposure. Thus
      prenatal exposure to loud sound especially noise alters the metabolic activity in
      the AuL which in turn can affect the functional development and later auditory
      associated behaviour.

PMID- 25049175
TI  - Targeting poly(ADP-ribose)polymerase1 in neurological diseases: A promising trove
      for new pharmacological interventions to enter clinical translation.
AB  - The highly conserved abundant nuclear protein poly(ADP-ribose)polymerase1 (PARP1)
      functions at the center of cellular stress response and is mainly implied in DNA
      damage repair mechanism. Apart from its involvement in DNA damage repair, it does
      sway multiple vital cellular processes such as cell death pathways, cell aging,
      insulator function, chromatin modification, transcription and mitotic apparatus
      function. Since brain is the principal organ vulnerable to oxidative stress and
      inflammatory responses, upon stress encounters robust DNA damage can occur and
      intense PARP1 activation may result that will lead to various CNS diseases. In
      the context of soaring interest towards PARP1 as a therapeutic target for newer
      pharmacological interventions, here in the present review, we are attempting to
      give a silhouette of the role of PARP1 in the neurological diseases and the
      potential of its inhibitors to enter clinical translation, along with its
      structural and functional aspects. 

PMID- 25049176
TI  - Detecting qualitative interactions in clinical trials with binary responses.
AB  - This study considers the detection of treatment-by-subset interactions in a
      stratified, randomised clinical trial with a binary-response variable. The focus
      lies on the detection of qualitative interactions. In addition, the presented
      method is useful more generally, as it can assess the inconsistency of the
      treatment effects among strata by using an a priori-defined inconsistency margin.
      The methodology presented is based on the construction of ratios of treatment
      effects. In addition to multiplicity-adjusted p-values, simultaneous confidence
      intervals are recommended to use in detecting the source and the amount of a
      potential qualitative interaction. The proposed method is demonstrated on a multi
      regional trial using the open-source statistical software R.

PMID- 25049177
TI  - Treating patients with real-time tumor tracking using the Vero gimbaled linac
      system: implementation and first review.
AB  - PURPOSE: To report on the first clinical application of a real-time tumor
      tracking (RTTT) solution based on the Vero SBRT gimbaled linac system for
      treatment of moving tumors. METHODS AND MATERIALS: A first group of 10 SBRT
      patients diagnosed with NSCLC or oligometastatic disease in lung or liver was
      treated with the RTTT technique. The PTV volumes and OAR exposure were
      benchmarked against the widely used ITV approach. Based on data acquired during
      execution of RTTT treatments, a first review was performed of the process.
      RESULTS: The 35% PTV volume reduction with RTTT of the studied single lesions
      SBRT irradiations of small target volumes is expected to result in a small (<1%)
      reduction of lung or liver NTCP. A GTV-PTV margin of 5.0mm was applied for
      treatment planning of RTTT. From patient data on residual geometric
      uncertainties, a CTV-PTV margin of 3.2mm was calculated. Reduction of the GTV-PTV
      margin below 5.0mm without better understanding of biological definition of tumor
      boundaries was discouraged. Total treatment times were reduced to 34.4 min on
      average. CONCLUSION: A considerable PTV volume reduction was achieved applying
      RTTT and time efficiency for respiratory correlated SBRT was reestablished with
      Vero RTTT.

PMID- 25049179
TI  - A 56-year-old man with necrotizing fasciitis.

PMID- 25049180
TI  - Coagulation: part 1.

PMID- 25049181
TI  - When good isn't good enough.

PMID- 25049182
TI  - Complacency, competition, and credibility.

PMID- 25049183
TI  - Vanderbilt LifeFlight celebrates 30 years of service.

PMID- 25049185
TI  - Air transport of patients with pneumothorax: is tube thoracostomy required before
      flight?
AB  - OBJECTIVE: It is conventionally thought that patients with pneumothorax (PTX)
      require tube thoracostomy (TT) before air medical transport (AMT), especially in
      unpressurized rotor-wing (RW) aircraft, to prevent deterioration from expansion
      of the PTX or development of tension PTX. We hypothesize that patients with PTX
      transported without TT tolerate RW AMT without serious deterioration, as defined
      by hypotension, hypoxemia, respiratory distress, intubation, bag valve mask
      ventilation, needle thoracostomy (NT), or cardiac arrest during transport.
      METHODS: We conducted a retrospective review of a case-series of trauma patients
      transported to a single Level 1 trauma center via RW with confirmed PTX and no
      TT. Using standardized abstraction forms, we reviewed charts for signs of
      deterioration. Those patients identified as having clinical deterioration were
      independently reviewed for the likelihood that the clinical deterioration was a
      direct consequence of PTX. RESULTS: During the study period, 66 patients with
      confirmed PTX underwent RW AMT with an average altitude gain of 1890 feet, an
      average barometric pressure 586-600 mmHg, and average flight duration of 28
      minutes. All patients received oxygen therapy; 14/66 patients (21%) were
      supported with positive pressure ventilation. Eleven of 66 patients (17%) had NT
      placed before flight and 4/66 (6%) had NT placed during flight. Four of 66
      patients (6% CI0.3-11.7) may have deteriorated during AMT as a result of PTX; all
      were successfully managed with NT. CONCLUSIONS: In this series, 6% of patients
      with PTX deteriorated as result of AMT without TT, yet all patients were managed
      successfully with NT. Routine placement of TT in patients with PTX before RW AMT
      may not be necessary. Further prospective evaluation is warranted.

PMID- 25049186
TI  - Stimulated saliva aminotransaminase alteration after experiencing acute hypoxia
      training.
AB  - OBJECTIVE: Acute cypobarih hypoxia is generally recognized to be the most serious
      single physiological hazard during flight at altitude. Simulation of acute
      hypoxia in an altitude chamber is used for the training of military aircrew.
      Acute hypobaric hypoxia affects critical organ systems in different manners. The
      purpose of this study was to investigate stimulated saliva glutamic pyruvic
      transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) alteration after
      the hypobaric hypoxia process. METHODS: A cross-sectional study was performed in
      44 normal healthy military aircrew conducted at the hypobaric chamber of
      physiology at the University of Medical Sciences, Tehran, Iran. The GPT and GOT
      activities were assayed in stimulated whole saliva before and after the
      experience of hypobaric hypoxia by the International Federation of Clinical
      Chemistry method. Statistical analysis of the Student t-test was performed.
      RESULTS: The mean stimulated saliva GPT activity was significantly higher after
      the experience of the hypobaric hypoxia process (2.83 +/- 0.34 vs. 0.42 +/- 0.029
      U/L, respectively; P = .001). Saliva GOT activity was also increased after this
      process (3.32 +/- 0.43 vs. 1.22 +/- 0.18 U/L, respectively; P = .001).
      CONCLUSION: Results suggest that subsequent to the experience of the hypobaric
      hypoxia process, there is a rise in the salivary activities of aminotransferases.

PMID- 25049187
TI  - Intraosseous access in trauma by air medical retrieval teams.
AB  - Trauma accounts for a significant portion of overall mortality globally.
      Hemorrhage is the second major cause of mortality in the prehospital environment.
      Air medical retrieval services throughout the world have been developed to help
      improve the outcomes of patients suffering from a broad range of medical
      conditions, including trauma. These services often utilize intraosseous (IO)
      devices as an alternative means for access of both medically ill and
      traumatically injured patients in austere environments. However, studies have
      suggested that IO access cannot reach acceptable rates for massive transfusion.
      We review the subject to find the answer of whether IO access should be performed
      by air medical teams in the prehospital setting, or would central venous (CVC)
      access be more appropriate? We decided to assess the literature for capacity of
      IO access to meet resuscitation requirements in the prehospital management of
      trauma. We also decided to compare the insertion and complication characteristics
      of IO and CVC access. 

PMID- 25049189
TI  - Past and current trends in intravenous therapy for hemorrhagic shock.
AB  - One issue that has generated controversy in the area of trauma care is the
      administration of isotonic intravenous crystalloid volume for patients suffering
      from traumatic hemorrhagic shock. This practice, once accepted as the standard
      for good medical care, has become regarded over the past decade as substandard.
      This article looks at the scientific basis for fluid resuscitation and evidence
      for declining use of this therapy. Finally, there is recent evidence that some
      level of intravenous fluid therapy is, in fact, beneficial. 

PMID- 25049188
TI  - Geographic information software programs' accuracy for interfacility air
      transport distances and time.
AB  - INTRODUCTION: This study aimed to evaluate consistency/predictability of
      interfacility flight times (IFFTs) and accuracy of geographical information
      system (GIS) software packages for estimating IFFT. METHODS: This retrospective
      study conducted by a program using a Bell 206 assessed the first 1000 IF
      transports occurring on 137 "runs" (ie, referring-receiving hospital pairings)
      made at least twice. GIS IFFT estimates using Google EarthTM (GE) and ArcGISTM
      (AG) were compared against actual IFFT using linear regression; univariate
      analysis included assessment of medians with 95% binomial exact confidence
      intervals (CIs). Interrater agreement for GIS was assessed with kappa. RESULTS:
      GE and AG estimates fell, respectively, within 1 mile of actual in 136/137 runs
      (99%, 95% CI 96%-100%) and 130/137 runs (95%, 95% CI 90%-98%). GE- and AG
      predicted IFFT strongly (P < .001) correlated with, underestimating by about 2
      minutes, actual IFFT (GE: r2 0.93, coefficient 0.98, 95% CI .97-1.00; AG: r2
      0.93; coefficient 0.98, 95% CI .96-1.0). GE and AG had statistically equivalent
      (kappa > .8), "almost-perfect," interrater agreement. CONCLUSION: IFFTs for same
      run helicopter EMS transports in our rural state setting are characterized by
      little variability. GIS is highly accurate in predicting IF logistics, with
      public-domain GE performing as well as more expensive AG.

PMID- 25049190
TI  - The electrocardiographic strip.

PMID- 25049192
TI  - Unilateral injection of Abeta25-35 in the hippocampus reduces the number of
      dendritic spines in hyperglycemic rats.
AB  - Alzheimer's disease (AD) is a neurodegenerative process exacerbated by several
      risk factors including impaired glucose metabolism in the brain that could cause
      molecular and neurochemical alterations in cognitive regions such as the
      hippocampus (Hp). Consequently, this process could cause neuronal morphological
      changes; however, the mechanism remains elusive. We induced chronic hyperglycemia
      after streptozotocin (STZ) administration. Then, we examined spatial learning and
      memory using the Morris water maze test and evaluated neuronal morphological
      changes using the Golgi-Cox stain procedure in hyperglycemic rats that received a
      Abeta25-35 unilateral injection into the Hp. Our results demonstrate that STZ
      combined with Abeta25-35 induced significant deficits in the spatial memory. In
      addition, we observed a significant reduction in the number of dendritic spines
      of pyramidal neurons in the dorsal Hp of rats with STZ plus Abeta25-35 . In
      conclusion, the reduced spine density of pyramidal neurons in the CA1 dorsal Hp
      could produce the spatial memory deficit observed in these animals. These results
      suggest that hyperglycemia can trigger Abeta-induced neurodegeneration and thus
      the appearance of AD symptoms would be accelerated. Synapse 68:585-594, 2014. (c)
      2014 Wiley Periodicals, Inc.

PMID- 25049194
TI  - Is spinal mobility in patients with spondylitis determined by age, structural
      damage, and inflammation?
AB  - OBJECTIVE: To explore the association between mobility, inflammation, and
      structural damage in ankylosing spondylitis (AS). METHODS: Patients with AS were
      included in a cross-sectional study in which spinal mobility was measured by the
      Bath Ankylosing Spondylitis Metrology Index (BASMI) and by the University of
      Cordoba Ankylosing Spondylitis Metrology Index (UCOASMI), based on an automated
      motion analysis. Structural damage was measured by the modified Stoke Ankylosing
      Spondylitis Spine Score (mSASSS), and activity by the Ankylosing Spondylitis
      Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease
      Activity (BASDAI). We analyzed the correlations between variables, as well as
      interaction by multiple linear regression models to reach a predictive equation.
      RESULTS: Fifty AS patients, mainly men in their mid-40s and with moderate levels
      of disease activity and structural damage, were included in the study. BASMI and
      UCOASMI scores showed a strong correlation (r = 0.89). UCOASMI scores correlated
      stronger than BASMI with structural damage (r = 0.72 versus r = 0.67) and
      patient's age (r = 0.68 versus r = 0.56). Correlations of mobility were weaker
      with disease activity by the ASDAS (r = 0.38) and BASDAI (r = 0.49), and disease
      duration (r = 0.40). Multiple linear regression showed that factors associated to
      mobility by UCOASMI were age, the BASDAI, mSASSS, ASDAS (0:<2.1, 1:>=2.1), and
      disease duration >15 years. The largest weight in the equation corresponded to
      the mSASSS. The association between the ASDAS and UCOASMI is dependent on disease
      duration. CONCLUSION: Mobility in AS is influenced by both structural damage and
      activity, but definitely also by age and disease duration. Improved mobility
      should be a relevant target in AS, even more prominently than activity, given its
      closer relation to structural damage.

PMID- 25049193
TI  - Shape-based virtual screening with volumetric aligned molecular shapes.
AB  - Shape-based virtual screening is an established and effective method for
      identifying small molecules that are similar in shape and function to a reference
      ligand. We describe a new method of shape-based virtual screening, volumetric
      aligned molecular shapes (VAMS). VAMS uses efficient data structures to encode
      and search molecular shapes. We demonstrate that VAMS is an effective method for
      shape-based virtual screening and that it can be successfully used as a prefilter
      to accelerate more computationally demanding search algorithms. Unique to VAMS is
      a novel minimum/maximum shape constraint query for precisely specifying the
      desired molecular shape. Shape constraint searches in VAMS are particularly
      efficient and millions of shapes can be searched in a fraction of a second. We
      compare the performance of VAMS with two other shape-based virtual screening
      algorithms a benchmark of 102 protein targets consisting of more than 32 million
      molecular shapes and find that VAMS provides a competitive trade-off between run
      time performance and virtual screening performance.

PMID- 25049195
TI  - Eating disorder symptoms and quality of life: where should clinicians place their
      focus in severe and enduring anorexia nervosa?
AB  - OBJECTIVE: The aim of this study was to examine the relationship between quality
      of life (QoL), weight, and eating disorder symptoms across treatment in
      individuals with severe and enduring anorexia nervosa (SE-AN). METHOD:
      Participants were 63 adult females with SE-AN presenting to an outpatient,
      multisite randomized clinical trial. QoL was assessed using three well-validated
      QoL questionnaire measures, the EDQOL, SF-12, and WSAS. Participants' weight and
      severity of symptoms was assessed by Eating Disorder Examination (EDE) and weekly
      BMI change. RESULTS: Predictors of QoL were evaluated in the context of
      concurrent, prospective,1 and lagged mixed-effects models. Changes in both BMI
      and EDE were found to significantly affect current and future QoL ratings.
      DISCUSSION: Findings suggest that improvements in QoL may be dependent on symptom
      change and weight gain. Treatments seeking solely to improve QoL may be unlikely
      to produce lasting change and clinicians should maintain a focus on weight and
      behavioral symptoms as much as on improvements in QoL.

PMID- 25049196
TI  - Ginger improves cognitive function via NGF-induced ERK/CREB activation in the
      hippocampus of the mouse.
AB  - Ginger (the rhizome of Zingiber officinale Roscoe) has been used worldwide for
      many centuries in cooking and for treatment of several diseases. The main
      pharmacological properties of ginger include anti-inflammatory,
      antihyperglycemic, antiarthritic, antiemetic and neuroprotective actions. Recent
      studies demonstrated that ginger significantly enhances cognitive function in
      various cognitive disorders as well as in healthy brain. However, the biochemical
      mechanisms underlying the ginger-mediated enhancement of cognition have not yet
      been studied in normal or diseased brain. In the present study, we assessed the
      memory-enhancing effects of dried ginger extract (GE) in a model of scopolamine
      induced memory deficits and in normal animals by performing a novel object
      recognition test. We found that GE administration significantly improved the
      ability of mice to recognize novel objects, indicating improvements in learning
      and memory. Furthermore, to elucidate the mechanisms of GE-mediated cognitive
      enhancement, we focused on nerve growth factor (NGF)-induced signaling pathways.
      NGF enzyme-linked immunosorbent assay analysis revealed that GE administration
      led to elevated NGF levels in both the mouse hippocampus and rat glioma C6 cells.
      GE administration also resulted in phosphorylation of extracellular-signal
      regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB), as
      revealed by Western blotting analysis. Neutralization of NGF with a specific NGF
      antibody inhibited GE-triggered activation of ERK and CREB in the hippocampus.
      Also, GE treatment significantly increased pre- and postsynaptic markers,
      synaptophysin and PSD-95, which are related to synapse formation in the brain.
      These data suggest that GE has a synaptogenic effect via NGF-induced ERK/CREB
      activation, resulting in memory enhancement. 

PMID- 25049199
TI  - Genetic testing for podocyte genes in sporadic focal segmental
      glomerulosclerosis.

PMID- 25049201
TI  - Estimation of scattered radiation in digital breast tomosynthesis.
AB  - Digital breast tomosynthesis (DBT) is a promising technique to overcome the
      tissue superposition limitations found in planar 2D x-ray mammography. However,
      as most DBT systems do not employ an anti-scatter grid, the levels of scattered
      radiation recorded within the image receptor are significantly higher than that
      observed in planar 2D x-ray mammography. Knowledge of this field is necessary as
      part of any correction scheme and for computer modelling and optimisation of this
      examination. Monte Carlo (MC) simulations are often used for this purpose,
      however they are computationally expensive and a more rapid method of calculation
      is desirable. This issue is addressed in this work by the development of a fast
      kernel-based methodology for scatter field estimation using a detailed realistic
      DBT geometry. Thickness-dependent scatter kernels, which were validated against
      the literature with a maximum discrepancy of 4% for an idealised geometry, have
      been calculated and a new physical parameter (air gap distance) was used to
      estimate more accurately the distribution of scattered radiation for a series of
      anthropomorphic breast phantom models. The proposed methodology considers, for
      the first time, the effects of scattered radiation from the compression paddle
      and breast support plate, which can represent more than 30% of the total
      scattered radiation recorded within the image receptor. The results show that the
      scatter field estimator can calculate scattered radiation images in an average of
      80 min for projection angles up to 25 degrees  with equal to or less than a 10%
      error across most of the breast area when compared with direct MC simulations. 

PMID- 25049200
TI  - Adiponectin receptor and adiponectin signaling in human tissue among patients
      with end-stage renal disease.
AB  - BACKGROUND: Adiponectin plasma levels in chronic kidney disease (CKD) are two to
      three times higher than in individuals with normal kidney function. Despite
      adiponectin's anti-diabetic, anti-inflammatory and anti-atherogenic properties,
      patients with CKD have insulin resistance, systemic inflammation and accelerated
      atherogenesis. Hence, although adiponectin production is increased by adipose
      tissue in end-stage renal disease (ESRD), it is unclear if its effects on
      metabolism remain intact. METHODS: To determine if there is adiponectin
      resistance in ESRD, we measured tissue levels of adiponectin receptor-1 (AdipoR1)
      and adiponectin downstream effectors in ESRD patients compared with normal kidney
      function controls. Blood and tissue samples were obtained from participants at
      the time of kidney transplantation or kidney donation. A follow-up blood sample
      was obtained 3-6 months after transplantation. RESULTS: AdipoR1 was higher in
      muscle and peripheral blood mononuclear cells collected from ESRD patients. There
      was also a nonsignificant increase in AdipoR1 in visceral fat of ESRD compared
      with controls. Compared with controls, phosphorylation of the adiponectin
      downstream effector adenosine monophosphate-activated protein kinase (AMPK) was
      higher in ESRD while acetyl-CoA carboxylase phosphorylation (ACC-P) and carnitine
      palmitoyl transferase-1 (CPT-1) levels were lower. In vitro, exposure of C2C12
      cells to uremic serum resulted in upregulation of AdipoR1 and increased
      phosphorylation of AMPK but decreased ACC-P and CPT-1 expression. CONCLUSION:
      Both our in vivo and in vitro observations indicate that uremia results in
      upregulation of AdipoR1 but adiponectin resistance at the post-receptor level.

PMID- 25049202
TI  - Prevalence of a history of overweight and obesity in adolescents with restrictive
      eating disorders.
AB  - PURPOSE: Although the relationship between increased body weight and eating
      disorders such as bulimia nervosa and binge eating disorder is well established,
      the relationship between overweight or obesity and eating disorders characterized
      by dietary restriction and/or weight loss such as anorexia nervosa (AN) is less
      well known. METHODS: To understand the prevalence of a history of overweight or
      obesity among treatment-seeking adolescents with restrictive eating disorders, a
      retrospective cohort study was conducted on all new patients aged 9-22 years
      diagnosed with either anorexia nervosa or eating disorder not otherwise specified
      characterized by weight loss and/or dietary restriction, seen in a specialty
      eating disorder clinic from January 2007 to July 2013. RESULTS: Of 179
      adolescents, 36.7% were found to have a body mass index (BMI) history above the
      85th percentile. Patients with a BMI history above the 85th percentile had a
      larger BMI decrease at presentation (p < .0001) and a longer duration of illness
      before presentation (p < .0001). There were no differences in the number of
      physical symptoms or eating disorder severity. CONCLUSIONS: Findings suggest that
      adolescents with a history of overweight or obesity represent a substantial
      portion of treatment-seeking adolescents with restrictive eating disorders,
      underscoring that extreme weight loss in adolescents is not healthy, regardless
      of whether the end weight is theoretically within a healthy range. Because eating
      disorders in adolescents who have history of overweight take longer to be
      identified, they consequently may have a poorer prognosis.

PMID- 25049203
TI  - European survey of diagnosis and management of the polycystic ovary syndrome:
      results of the ESE PCOS Special Interest Group's Questionnaire.
AB  - BACKGROUND: There is evidence for differences between endocrinologists and other
      specialists in their approach to diagnosis and management of the polycystic ovary
      syndrome (PCOS). OBJECTIVE: A mailed survey consisting of a simple questionnaire
      aiming to understand current practice for diagnosis and management of the PCOS by
      specialists across Europe. METHODS: The questionnaire consisted of 23 questions
      grouped to achieve information on i) the general characteristics of the
      respondents, ii) patients with PCOS seen by endocrinologists, iii) the main
      diagnostic criteria, iv) biochemical parameters used in the differential
      diagnosis of hyperandrogenism, v) long-term concerns, and, finally vi) treatment
      choices. A total of 357 questionnaires representing 13.3% of the members of
      European Society of Endocrinology (ESE) were available for final analysis; 93% of
      the respondents were endocrinologists RESULTS: In relation to the diagnostic
      criteria, respondents were most likely to select menstrual irregularity as the
      most frequent criteria used for the diagnosis of PCOS although very high rates
      were achieved for the use of hirsutism and biochemical hyperandrogenism. It
      therefore appears that the NIH criteria were followed by the majority of
      respondents. The most frequent biochemical parameters in the differential
      diagnosis of hyperandrogenism were total testosterone or free androgen index.
      Obesity and type 2 diabetes were regarded as the principal long-term concerns for
      PCOS. The most common treatments for patients with PCOS were metformin (33%),
      lifestyle modification (25%), and oral contraceptives (22%). More direct
      treatments of infertility include clomiphene citrate alone or in combination with
      metformin, prescribed by 9 and 23%, respectively, whereas only 6% used other
      methods for induction of ovulation. CONCLUSION: The survey produced by ESE is a
      good start for evaluating the perspective in the diagnosis and treatment of PCOS
      by endocrinologists in Europe.

PMID- 25049204
TI  - Hepatocyte growth factor-like protein is a positive regulator of early mammary
      gland ductal morphogenesis.
AB  - The Ron receptor tyrosine kinase regulates multiple cellular processes and is
      important during mammary gland development and tumor progression. Hepatocyte
      growth factor-like protein [HGFL] is the only known ligand for the Ron receptor
      and recent studies have identified major roles for HGFL during breast cancer
      metastasis. Understanding the functional importance HGFL during mammary gland
      development will provide significant insights onto its contribution during tumor
      development and metastasis. In this study, we assessed the role of HGFL during
      postnatal mammary gland development using mice that were either proficient [HGFL
      +/+] or deficient [HGFL-/-] for HGFL. Postnatal ductal morphology and stromal
      cell associations were analyzed at multiple time points through puberty until
      adulthood. HGFL deficiency resulted in several mammary gland developmental
      defects including smaller terminal end buds [TEBs], significantly fewer TEBs, and
      delayed ductal outgrowth during early puberty. Additionally, HGFL deficient
      animals exhibited significantly altered TEB epithelial cell turnover with
      decreased proliferation and increased apoptosis coupled with decreased TEB
      diameter. Macrophage recruitment to the TEBs was also significantly decreased in
      the HGFL-/- mice compared to controls. Moreover, the levels of STAT3 mRNA as well
      as the phosphorylation status of this protein were lower in the HGFL-/- mammary
      glands compared to controls. Taken together, our data provide the first evidence
      for HGFL as a positive regulator of mammary gland ductal morphogenesis by
      controlling overall epithelial cell turnover, macrophage recruitment, and STAT3
      activation in the developing mammary gland. With a function in early mammary
      gland development, HGFL represents a potential target for the development of
      novel breast cancer therapies. 

PMID- 25049205
TI  - CD8+ T cell responses specific for hepatitis B virus core protein in patients
      with chronic hepatitis B virus infection.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection includes a set of
      heterogeneous clinical patterns, and core-protein-specific T cell response is
      important for virus control and disease progression, yet is not well elucidated.
      OBJECTIVES: To analyze the phenotypic and functional profiles of HBV-core-protein
      specific CD8+ T cells in different clinical patterns of chronic HBV infection.
      STUDY DESIGN: A total of 46 HBV patients were recruited and classified according
      to their clinical status. CD8+ T cell responses in different patterns of chronic
      HBV infections were tested with flow cytometry using overlapping 15-mer peptides
      covering HBV core protein. Meanwhile, the CCR7/CD27 phenotypes of these CD8+ T
      cells were also determined. RESULTS: Frequencies of gamma interferon (IFN-gamma)
      positive CD8+ T cells in inactive HBV surface antigen (HBsAg) carriers in
      response to the core protein peptide pools were generally stronger than those of
      chronic HBV carriers and resolved individuals, especially with regards to peptide
      pool C13-C24. Moreover, phenotypic studies further highlighted the group of CD8+
      CCR7-CD27+ T memory cells, which showed significantly higher levels of IFN-gamma
      secretion in inactive HBsAg carriers than those in chronic hepatitis B patients,
      chronic HBV carriers and resolved individuals. CONCLUSIONS: Core-protein-specific
      T cell response plays an important role in chronic HBV infection. Inactive HBsAg
      carriers showed a much stronger core-protein-specific cytotoxic T cell response
      than other types of chronically infected patients. CD8+ CCR7-CD27+ T memory
      lymphocytes may be crucial in the immune pathogenesis of chronic HBV infection.

PMID- 25049206
TI  - Acute acalculous cholecystitis, a rare complication of Epstein-Barr virus primary
      infection: report of two cases and review.
AB  - We described two cases of acalculous cholecystitis (AAC), due to EBV primary
      infection in two young Caucasian women and we reviewed other reported cases. In
      contrast with AAC of other etiologies, antibiotics and surgery are not useful in
      the management of AAC secondary to EBV.

PMID- 25049207
TI  - Merkel cell polyomavirus: its putative involvement in a particular subset of
      cutaneous lymphoma with possibly unfavorable outcome.
AB  - BACKGROUND: A major etiologic hypothesis in primary cutaneous T-cell lymphomas is
      a defective lymphocyte apoptosis after antigenic activation, which could be
      induced by various infectious agents. OBJECTIVE: To investigate the presence of
      the possibly lymphotropic and folliculotropic Merkel cell polyomavirus (MCPyV)
      DNA and proteins in folliculotropic mycosis fungoides (fMF). STUDY DESIGN: Fresh
      frozen and fixed skin biopsies were collected in lesional and non-lesional skin
      from 24 fMF patients, in lesional skin from 22 patients with various T-cell
      mediated skin benign infiltrates (TSBI) and in normal-appearing skin from 22
      healthy individuals (HI). Detection and quantification of MCPyV DNA were carried
      out using real-time PCR; MCPyV genome integration status was presumed through a
      previously described differential real-time PCR (MCPyV DeltaC-TAg) targeting a
      constantly conserved sequence versus an integration-induced deleted sequence. The
      MCPyV proteins expression was assessed by immunohistochemistry using antibodies
      targeting a tumoral antigen or a capsid protein. RESULTS: Although MCPyV DNA was
      similarly detected in lesional versus non-lesional fMF samples (50% each), in
      36.4% HI and 40.9% TSBI; viral load was significantly higher in fMF lesional
      samples versus HI and TSBI. The integration of the viral genome appeared
      unlikely. The MCPyV proteins expression was exclusively observed inside skin
      appendages in 18.2% of the fMF lesional skin samples. CONCLUSION: MCPyV genome
      detection rate was similar in all skin samples, but MCPyV viral load was
      significantly higher in fMF lesions versus TSBI and HI, although the viral genome
      was probably not integrated. Episomal MCPyV DNA may be expressed in skin
      appendages in fMF.

PMID- 25049208
TI  - Neural correlates of visuospatial consciousness in 3D default space: insights
      from contralateral neglect syndrome.
AB  - One of the most compelling questions still unanswered in neuroscience is how
      consciousness arises. In this article, we examine visual processing, the parietal
      lobe, and contralateral neglect syndrome as a window into consciousness and how
      the brain functions as the mind and we introduce a mechanism for the processing
      of visual information and its role in consciousness. We propose that
      consciousness arises from integration of information from throughout the body and
      brain by the thalamus and that the thalamus reimages visual and other sensory
      information from throughout the cortex in a default three-dimensional space in
      the mind. We further suggest that the thalamus generates a dynamic default three
      dimensional space by integrating processed information from corticothalamic
      feedback loops, creating an infrastructure that may form the basis of our
      consciousness. Further experimental evidence is needed to examine and support
      this hypothesis, the role of the thalamus, and to further elucidate the mechanism
      of consciousness. 

PMID- 25049209
TI  - An LC-MS method for simultaneous determination of five iridoids from Zhi-zi-chi
      Decoction in rat brain microdialysates and tissue homogenates: towards an in
      depth study for its antidepressive activity.
AB  - Zhi-zi-chi Decoction has been clinically utilized for the treatment of depression
      for more than thousand years. In order to investigate the possible bioactive
      components that could pass through the blood brain barrier (BBB) and the
      mechanism of antidepressant, a sensitive LC-MS method was developed to detect the
      ingredients (geniposide, scandoside methyl ester, gardenoside, deacetyl
      asperulosidic acid methyl ester and genipin-1-beta-gentiobioside) in rat brain
      microdialysates and tissue homogenates samples (hippocampus, hypothalamus,
      premotor cortex, striatum, oblongata and cerebellum). Method development and
      validation are described in terms of calibration curves, extraction yield, lower
      limit of quantification (LLOQ), precision, accuracy, intra- and inter-day
      variability, which are in accordance with the requirements. Microdialysis in
      hippocampus demonstrated that the five iridoids possessed complete
      pharmacokinetic process while brain tissue homogenate method testified the
      distribution regularity in brain. The work clarified that the five iridoids, as
      antidepressant ingredients, could pass through the BBB, distribute targeted and
      possess complete pharmacokinetics in brain. These observations, along with the
      large database of rat brain microdialysates and tissue homogenates data, could
      enable future efforts aimed to improve our understanding of the relationship
      between bioactive ingredients and clinical therapy of depression.

PMID- 25049210
TI  - Determination of total and unbound concentrations of lopinavir in plasma using
      liquid chromatography-tandem mass spectrometry and ultrafiltration methods.
AB  - Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in
      human plasma. This study was designed to develop an ultrafiltration method to
      measure the unbound concentrations of lopinavir overcoming the non-specific
      binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      for the determination of total concentrations of lopinavir in plasma was
      developed and validated, and an adaptation was also optimized and validated for
      the determination of unbound concentrations. The chromatographic separation was
      performed with a C18 column (100 mm * 2.1mm i.d., 5 MUm particle size) using a
      mobile phase containing deionized water with formic acid, and acetonitrile, with
      gradient elution at a flow-rate of 350 MUL min(-1). Identification of the
      compounds was performed by multiple reaction monitoring, using electrospray
      ionization in positive ion mode. The method was validated over a clinical range
      of 0.01-1 MUg/mL for human plasma ultrafiltrate and 0.1-15 MUg/mL in human
      plasma. The inter and intra-assay accuracies and precisions were between 0.23%
      and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for
      plasma ultrafiltrate (unbound concentration). The ultrafiltration method
      described allows an accurate separation of the unbound fraction of lopinavir,
      circumscribing the loss of drug by nonspecific binding (NSB), and the validated
      LC-MS/MS methodology proposed is suitable for the determination of total and
      unbound concentrations of lopinavir in clinical practice.

PMID- 25049211
TI  - Enantioselective HPLC determination and pharmacokinetic study of secnidazole
      enantiomers in rats.
AB  - Secnidazole is a long-lasting nitroimidazole antimicrobial agent that is used as
      racemic mixture in clinical settings. We developed and validated an
      enantioselective high-performance liquid chromatography method to determine
      secnidazole enantiomers in rat plasma. Secnidazole enantiomers and S-(-)
      ornidazole (internal standard) were extracted from 50 MUL of rat plasma using
      diethyl ether-dichloromethane (3:2, v/v). Baseline resolution (Rs=2.45) was
      achieved within 7.0 min on a Chiral-AGP column (150 mm * 4.0mm, 5 MUm) at 20
      degrees C. The mobile phase consisted of 10mM ammonium acetate-methanol (96:4,
      v/v) and was delivered at a flow rate of 0.5 mL/min with ultraviolet detection at
      318 nm. The method was linear over the concentration range 0.500-100 MUg/mL for
      both enantiomers. The lower limit of quantification was 0.500 MUg/mL for both
      enantiomers. The relative standard deviation values for intra- and inter-day
      precision were 0.8-8.6 and 1.8-8.2% for S-(+)-secnidazole and R-(-)-secnidazole,
      respectively. The relative error values of accuracy ranged from -7.8 to 1.1% for
      S-(+)-secnidazole and from -7.3 to -0.1% for R-(-)-secnidazole. The method was
      successfully used to determine the pharmacokinetic properties of secnidazole
      enantiomers in rats after administration of the racemate and individual
      enantiomers. The pharmacokinetic results indicate that the disposition of
      secnidazole enantiomers is not stereoselective and chiral inversion and
      enantiomer-enantiomer interaction do not occur in rats.

PMID- 25049212
TI  - Simulated moving bed purification of flaxseed oil orbitides: unprecedented
      separation of cyclolinopeptides C and E.
AB  - The purification and enrichment of most natural products with potential
      pharmaceutical applications has been performed mainly employing conventional
      batch-mode chromatographic processes. There is a growing interest in use of
      simulated moving bed (SMB) chromatography for natural product enrichment as this
      method enables conservation of mobile phase, while increasing productivity of
      chromatography medium. SMB increases yield while decreasing cost.
      Cyclolinopeptides C ([1-9-NaC],[1-MetO]-CLB, 3) and E ([1-8-NaC],[1-MetO]-CLE, 8)
      were extracted as a mixture from flaxseed oil and then enriched using a three
      zone simulated moving bed. The current research extends the SMB technology to
      enrichment of cyclolinopeptides (CLs), a group of biologically active hydrophobic
      cyclic peptides that occur in flaxseed oil. Of interest are [1-9-NaC],[1-MetO]
      CLB (3) and [1-8-NaC],[1-MetO]-CLE (8) that provide synthetic scaffolds for
      modified CLs. The influence of flow rate (feed, desorbent, and extract) on the
      separation of [1-9-NaC],[1-MetO]-CLB (3) and [1-8-NaC],[1-MetO]-CLE (8) was
      investigated.

PMID- 25049213
TI  - Determination of LBPT in human plasma by high performance liquid chromatography
      tandem mass spectrometry.
AB  - A rapid and selective HPLC-MS/MS method was developed for the determination of
      LBPT in human plasma. The analyte was extracted from plasma samples by solid
      phase extraction and then chromatographed on a C18 analytical column. The mobile
      phase consisted of acetonitrile-10mM ammonium formate in 0.1% formic acid (30:70,
      v/v) and the flow rate was 0.2 mL/min. The detection was performed on a triple
      quadrupole tandem mass spectrometer in multiple reactions monitoring (MRM) mode
      using positive electrospray ionization (ESI). The method was validated over the
      concentration range of 0.2-100 ng/mL. Inter- and intra-day precision (RSD %) were
      less than 9.2% and the accuracy (RE %) ranged from 0 to 11.0%. The lower limit of
      quantitation (LLOQ) was 0.2 ng/mL. The extraction recovery was on average 75% and
      the detection was not affected by the matrix. The method was successfully applied
      to the pharmacokinetic study of LBPT in healthy Chinese subjects.

PMID- 25049214
TI  - Parallel ultra high pressure liquid chromatography-mass spectrometry for the
      quantification of HIV protease inhibitors using dried spot sample collection
      format.
AB  - An assay was developed and validated for the quantification of eight protease
      inhibitors (indinavir (IDV), ritonavir (RTV), lopinavir (LPV), saquinavir (SQV),
      amprenavir (APV), nelfinavir (NFV), atazanavir (AZV) and darunavir (DRV)) in
      dried plasma spots using parallel ultra-high performance liquid chromatography
      and mass spectrometry detection in the multiple reaction monitoring mode. For
      each analyte an isotopically labeled internal standard was used and the assay
      based on liquid-solid extraction the area response ratio (analyte/IS) was found
      to be linear; from 0.025 MUg/ml to 20 MUg/ml for IDV, SQV, DRV, AZV, LPV, from
      0.025 MUg/ml to 10 MUg/ml for NFV, APV and from 0.025 MUg/ml to 5 MUg/ml for RTV
      using 15 MUl of plasma spotted on filter paper placed in a sample tube. The total
      analysis time was of 4 min and inter-assay accuracies and precisions were in the
      range of 87.7-109% and 2.5-11.8%, respectively. On dried plasma spots all
      analytes were found to be stable for at least 7 days. Practicability of the assay
      to blood was also demonstrated. The sample drying process could be reduced to 5
      min using a commercial microwave system without any analyte degradation. Together
      with quantification, confirmatory analysis was performed on representative
      clinical samples.

PMID- 25049215
TI  - Gender differences in smoking among U.S. working adults.
AB  - BACKGROUND: Cigarette smoking remains a leading cause of morbidity and mortality.
      Although gender differences in cigarette smoking in the U.S. population have been
      documented, information on these differences among working adults is limited.
      PURPOSE: To describe the current smoking prevalence by gender among working U.S.
      adults and examine gender differences in smoking by occupation. METHODS: The 2004
      2011 National Health Interview Survey data for adults aged >=18 years that were
      working in the week prior to the interview (N=132,215) were analyzed in 2013.
      Current cigarette smokers were those who smoked at least 100 cigarettes in their
      lifetime and currently smoke every day or some days. RESULTS: During 2004-2011,
      an estimated 22.8% of men workers and 18.3% of women workers were current
      smokers. Of the current smokers, women workers had higher odds of being an
      everyday smoker (prevalence OR [POR]=1.17, 95% CI=1.09, 1.26); having poor self
      rated emotional health (POR=1.28, 95% CI=1.15, 1.41); and having chronic
      obstructive pulmonary disease (POR=2.45, 95% CI=2.14, 2.80), heart disease
      (POR=1.27, 95% CI=1.12, 1.45), and current asthma (POR=2.21, 95% CI=1.96, 2.49)
      compared with men workers. Women in "supervisors, construction, and extraction"
      (38.9%) occupations and men in "extraction" (40.5%) occupations had the highest
      smoking prevalence. CONCLUSION: Among working adults, women had lower prevalence
      of smoking than men, yet women who smoke were more likely than men to have
      adverse health outcomes, including self-rated poorer physical and emotional
      health.

PMID- 25049216
TI  - Non-exercise physical activity and survival: English longitudinal study of
      ageing.
AB  - BACKGROUND: The activity patterns of older adults include more light/mild
      intensity or "non-exercise" activity and less moderate- to vigorous-intensity
      activity. The health benefits of this type of activity pattern remain unclear.
      PURPOSE: To examine dose-response associations between physical activity and
      survival using time-varying analysis to understand the importance of "non
      exercise" activity for survival in older adults. METHODS: Participants (N=10,426)
      were drawn from The English Longitudinal Study of Ageing, a representative sample
      of men and women aged >=50 years living in England. Participant data were linked
      with death records from the National Health Service registries from 2002 to 2011.
      Analyses were conducted in 2013. Cox proportional hazards models were used to
      estimate the risk of death according to time-varying estimates of physical
      activity. RESULTS: Over an average follow-up of 7.8 years (median follow-up, 8.5
      years), there were 1,896 deaths. In models adjusted for comorbidities,
      psychosocial factors, smoking, and obesity, there was a dose-response association
      between time-varying physical activity and mortality, with the greatest survival
      benefit in vigorously active participants. However, participating in mild ("non
      exercise")-intensity physical activity was also associated with a lower risk of
      all-cause mortality (hazard ratio [HR]=0.76, 95% CI=0.69, 0.83); cardiovascular
      mortality (HR=0.74, 95% CI=0.64, 0.85); and death by other causes (HR=0.67, 95%
      CI=0.58, 0.78). Time-varying models produced stronger, more robust estimates than
      models using a single measurement of physical activity at baseline. CONCLUSIONS:
      Older adults gain health benefits from participating in regular "non-exercise"
      physical activity, although the greatest benefits are observed for more vigorous
      activity.

PMID- 25049217
TI  - Are food and beverage purchases in households with preschoolers changing?: a
      longitudinal analysis from 2000 to 2011.
AB  - BACKGROUND: U.S. dietary studies from 2003 to 2010 show decreases in children's
      caloric intake. We examined purchases of consumer packaged foods/beverages in the
      U.S. between 2000 and 2011 among households with children aged 2-5 years.
      PURPOSE: To describe changes in consumer packaged goods (CPG) purchases between
      2000 and 2011 after adjusting for economic indicators, and explore differences by
      race, education, and household income level. METHODS: CPG purchase data were
      obtained for 42,753 U.S. households with one or more child aged 2-5 years using
      the Nielsen Homescan Panel. Top sources of purchased calories were grouped, and
      random effects regression was used to model the relationship between calories
      purchased from each group and race, female head of household education, and
      household income. Models adjusted for household composition, market-level
      unemployment rate, prices, and quarter, with Bonferroni correction for multiple
      comparisons (alpha=0.05). RESULTS: Between 2000 and 2011, adjusted total calories
      purchased from foods (-182 kcal/day) and beverages (-100 kcal/day) declined
      significantly. Decreases in purchases of milk (-40 kcal); soft drinks (-27
      kcal/day); juice and juice drinks (-24 kcal/day); grain-based desserts (-24
      kcal/day); savory snacks (-17 kcal/day); and sweet snacks and candy (-13
      kcal/day) were among the major changes. Changes in CPG purchases differed
      significantly by race, female head of household education, and household income.
      CONCLUSIONS: Trends in CPG purchases suggest that solid fats and added sugars are
      decreasing in the food supply of U.S. preschoolers. Pronounced differences by
      race, education, and household income persist.

PMID- 25049219
TI  - Comparison of volumetric breast density estimations from mammography and thorax
      CT.
AB  - Breast density has become an important issue in current breast cancer screening,
      both as a recognized risk factor for breast cancer and by decreasing screening
      efficiency by the masking effect. Different qualitative and quantitative methods
      have been proposed to evaluate area-based breast density and volumetric breast
      density (VBD). We propose a validation method comparing the computation of VBD
      obtained from digital mammographic images (VBDMX) with the computation of VBD
      from thorax CT images (VBDCT). We computed VBDMX by applying a conversion
      function to the pixel values in the mammographic images, based on models
      determined from images of breast equivalent material. VBDCT is computed from the
      average Hounsfield Unit (HU) over the manually delineated breast volume in the CT
      images. This average HU is then compared to the HU of adipose and fibroglandular
      tissues from patient images. The VBDMX method was applied to 663 mammographic
      patient images taken on two Siemens Inspiration (hospL) and one GE Senographe
      Essential (hospJ). For the comparison study, we collected images from patients
      who had a thorax CT and a mammography screening exam within the same year. In
      total, thorax CT images corresponding to 40 breasts (hospL) and 47 breasts
      (hospJ) were retrieved. Averaged over the 663 mammographic images the median
      VBDMX was 14.7% . The density distribution and the inverse correlation between
      VBDMX and breast thickness were found as expected. The average difference between
      VBDMX and VBDCT is smaller for hospJ (4%) than for hospL (10%). This study shows
      the possibility to compare VBDMX with the VBD from thorax CT exams, without
      additional examinations. In spite of the limitations caused by poorly defined
      breast limits, the calibration of mammographic images to local VBD provides
      opportunities for further quantitative evaluations. 

PMID- 25049220
TI  - Local transient unfolding of native state PAI-1 associated with serpin
      metastability.
AB  - The metastability of the native fold makes serpin (serine protease inhibitor)
      proteins prone to pathological conformational change, often by insertion of an
      extra beta-strand into the central beta-sheet A. How this insertion is made
      possible is a hitherto unresolved question. By the use of advanced
      hydrogen/deuterium-exchange mass spectrometry (HDX-MS) it is shown that the
      serpin plasminogen activator inhibitor 1 (PAI-1) transiently unfolds under native
      condition, on a second-to-minute time scale. The unfolding regions comprise beta
      strand 5A as well as the underlying hydrophobic core, including beta-strand 6B
      and parts of helices A, B, and C. Based thereon, a mechanism is proposed by which
      PAI-1 makes transitions through progressively more unfolded states along the
      reaction coordinate to the inactive, so-called latent form. Our results highlight
      the profound utility of HDX-MS in detecting sparsely populated, transiently
      unfolded protein states. 

PMID- 25049218
TI  - Environments perceived as obesogenic have lower residential property values.
AB  - BACKGROUND: Studies have tried to link obesity rates and physical activity with
      multiple aspects of the built environment. PURPOSE: To determine the relation
      between residential property values and multiple perceived (self-reported)
      measures of the obesogenic environment. METHODS: The Seattle Obesity Study (SOS)
      used a telephone survey of a representative, geographically distributed sample of
      2,001 King County adults, collected in 2008-2009 and analyzed in 2012-2013. Home
      addresses were geocoded. Residential property values at the tax parcel level were
      obtained from the King County tax assessor. Mean residential property values
      within a 10-minute walk (833-m buffer) were calculated for each respondent. Data
      on multiple perceived measures of the obesogenic environment were collected by
      self-report. Correlations and multivariable linear regression analyses,
      stratified by residential density, were used to examine the associations among
      perceived environmental measures, property values, and BMI. RESULTS: Perceived
      measures of the environment such as crime, heavy traffic, and proximity to bars,
      liquor stores, and fast food were all associated with lower property values. By
      contrast, living in neighborhoods that were perceived as safe, quiet, clean, and
      attractive was associated with higher property values. Higher property values
      were associated, in turn, with lower BMIs among women. The observed associations
      between perceived environment measures and BMI were largely attenuated after
      accounting for residential property values. CONCLUSIONS: Environments perceived
      as obesogenic are associated with lower property values. Studies in additional
      locations need to explore to what extent other perceived environment measures can
      be reflected in residential property values.

PMID- 25049221
TI  - Improving PET spatial resolution and detectability for prostate cancer imaging.
AB  - Prostate cancer, one of the most common forms of cancer among men, can benefit
      from recent improvements in positron emission tomography (PET) technology. In
      particular, better spatial resolution, lower noise and higher detectability of
      small lesions could be greatly beneficial for early diagnosis and could provide a
      strong support for guiding biopsy and surgery. In this article, the impact of
      improved PET instrumentation with superior spatial resolution and high
      sensitivity are discussed, together with the latest development in PET
      technology: resolution recovery and time-of-flight reconstruction. Using
      simulated cancer lesions, inserted in clinical PET images obtained with
      conventional protocols, we show that visual identification of the lesions and
      detectability via numerical observers can already be improved using state of the
      art PET reconstruction methods. This was achieved using both resolution recovery
      and time-of-flight reconstruction, and a high resolution image with 2 mm pixel
      size. Channelized Hotelling numerical observers showed an increase in the area
      under the LROC curve from 0.52 to 0.58. In addition, a relationship between the
      simulated input activity and the area under the LROC curve showed that the
      minimum detectable activity was reduced by more than 23%. 

PMID- 25049223
TI  - Factors influencing the accuracy of beam range estimation in proton therapy using
      prompt gamma emission.
AB  - In-vivo imaging is a strategy to monitor the range of protons inside the patient
      during radiation treatment. A possible method of in-vivo imaging is detection of
      secondary 'prompt' gamma (PG) photons outside the body, which are produced by
      inelastic proton-nuclear interactions inside the patient. In this paper,
      important parameters influencing the relationship between the PG profile and
      percentage depth dose (PDD) in a uniform cylindrical phantom are explored. Monte
      Carlo simulations are performed with the new Geant4 based code TOPAS for mono
      energetic proton pencil beams (range: 100-250 MeV) and an idealized PG detector.
      PG depth profiles are evaluated using the inflection point on a sigmoid fit in
      the fall-off region of the profile. A strong correlation between the inflection
      point and the proton range determined from the PDD is found for all conditions.
      Variations between 1.5 mm and 2.7 mm in the distance between the proton range and
      the inflection point are found when either the mass density, phantom diameter, or
      detector acceptance angle is changed. A change in cut-off energy of the detector
      could induce a range difference of maximum 4 mm. Applying time-of-flight
      discrimination during detection, changing the primary energy of the beam or
      changing the elemental composition of the tissue affects the accuracy of the
      range prediction by less than 1 mm. The results indicate that the PG signal is
      rather robust to many parameter variations, but millimetre accurate range
      monitoring requires all medium and detector properties to be carefully taken into
      account. 

PMID- 25049222
TI  - Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the
      signaling lipid PIP2 and Na+ in a reconstituted system.
AB  - GIRK channels control spike frequency in atrial pacemaker cells and inhibitory
      potentials in neurons. By directly responding to G proteins, PIP2 and Na(+), GIRK
      is under the control of multiple signaling pathways. In this study, the mammalian
      GIRK2 channel has been purified and reconstituted in planar lipid membranes and
      effects of Galpha, Gbetagamma, PIP2 and Na(+) analyzed. Gbetagamma and PIP2 must
      be present simultaneously to activate GIRK2. Na(+) is not essential but modulates
      the effect of Gbetagamma and PIP2 over physiological concentrations.
      Galphai1(GTPgammaS) has no effect, whereas Galphai1(GDP) closes the channel
      through removal of Gbetagamma. In the presence of Gbetagamma, GIRK2 opens as a
      function of PIP2 mole fraction with Hill coefficient 2.5 and an affinity that
      poises GIRK2 to respond to natural variations of PIP2 concentration. The dual
      requirement for Gbetagamma and PIP2 can help to explain why GIRK2 is activated by
      Gi/o, but not Gq coupled GPCRs.

PMID- 25049224
TI  - A microchannel flow model for soft tissue elasticity.
AB  - A number of advances, including imaging of tissue displacements, have increased
      our ability to make measurements of tissue elastic properties of animal and human
      tissues. Accordingly, the question is increasingly asked, 'should our data be fit
      to a viscoelastic model, and if so which one?' In this paper we focus solely on
      soft tissues in a functional (non-pathological) state, and develop a model of
      elastic behavior that is based on the flow of viscous fluids through the
      extensive network of tissue microchannels in response to applied stress. This
      behavior can be captured in a 2-parameter model, and the model appears to predict
      the stress-relaxation behavior and the dispersive shear wave behavior of bovine
      liver specimens and other soft tissues and phantoms. The relationship of the
      microchannel flow model to more traditional models is also examined. 

PMID- 25049225
TI  - The PML-associated protein DEK regulates the balance of H3.3 loading on chromatin
      and is important for telomere integrity.
AB  - Histone variant H3.3 is deposited in chromatin at active sites, telomeres, and
      pericentric heterochromatin by distinct chaperones, but the mechanisms of
      regulation and coordination of chaperone-mediated H3.3 loading remain largely
      unknown. We show here that the chromatin-associated oncoprotein DEK regulates
      differential HIRA- and DAAX/ATRX-dependent distribution of H3.3 on chromosomes in
      somatic cells and embryonic stem cells. Live cell imaging studies show that
      nonnucleosomal H3.3 normally destined to PML nuclear bodies is re-routed to
      chromatin after depletion of DEK. This results in HIRA-dependent widespread
      chromatin deposition of H3.3 and H3.3 incorporation in the foci of
      heterochromatin in a process requiring the DAXX/ATRX complex. In embryonic stem
      cells, loss of DEK leads to displacement of PML bodies and ATRX from telomeres,
      redistribution of H3.3 from telomeres to chromosome arms and pericentric
      heterochromatin, induction of a fragile telomere phenotype, and telomere
      dysfunction. Our results indicate that DEK is required for proper loading of ATRX
      and H3.3 on telomeres and for telomeric chromatin architecture. We propose that
      DEK acts as a "gatekeeper" of chromatin, controlling chromatin integrity by
      restricting broad access to H3.3 by dedicated chaperones. Our results also
      suggest that telomere stability relies on mechanisms ensuring proper histone
      supply and routing.

PMID- 25049226
TI  - Cotranscriptional histone H2B monoubiquitylation is tightly coupled with RNA
      polymerase II elongation rate.
AB  - Various histone modifications decorate nucleosomes within transcribed genes.
      Among these, monoubiquitylation of histone H2B (H2Bub1) and methylation of
      histone H3 on lysines 36 (H3K36me2/3) and 79 (H3K79me2/3) correlate positively
      with gene expression. By measuring the progression of the transcriptional
      machinery along genes within live cells, we now report that H2B
      monoubiquitylation occurs cotranscriptionally and accurately reflects the advance
      of RNA polymerase II (Pol II). In contrast, H3K36me3 and H3K79me2 are less
      dynamic and represent Pol II movement less faithfully. High-resolution ChIP-seq
      reveals that H2Bub1 levels are selectively reduced at exons and decrease in an
      exon-dependent stepwise manner toward the 3' end of genes. Exonic depletion of
      H2Bub1 in gene bodies is highly correlated with Pol II pausing at exons,
      suggesting elongation rate changes associated with intron-exon structure. In
      support of this notion, H2Bub1 levels were found to be significantly correlated
      with transcription elongation rates measured in various cell lines. Overall, our
      data shed light on the organization of H2Bub1 within transcribed genes and single
      out H2Bub1 as a reliable marker for ongoing transcription elongation.

PMID- 25049227
TI  - Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway.
AB  - The ubiquitin-proteasome system and autophagy are crucially important for
      proteostasis in cells. These pathways are interdependent, and dysfunction in
      either pathway causes accumulation of ubiquitin-positive aggregates, a hallmark
      of human pathological conditions. To elucidate in vivo compensatory action(s)
      against proteasomal dysfunction, we developed mice with reduced proteasome
      activity in their livers. The mutant mice exhibited severe liver damage,
      accompanied by formation of aggregates positive for ubiquitin and p62/Sqstm1, an
      adaptor protein for both selective autophagy and the anti-oxidative Keap1-Nrf2
      pathway. These aggregates were selectively entrapped by autophagosomes, and
      pathological features of livers with impaired proteasome activity were
      exacerbated by simultaneous suppression of autophagy. In contrast, concomitant
      loss of p62/Sqstm1 had no apparent effect on the liver pathology though
      p62/Sqstm1 was indispensable for the aggregates formation. Furthermore, defective
      proteasome function led to transcriptional activation of the Nrf2, which served
      as a physiological adaptation. Our in vivo data suggest that cells contain
      networks of cellular defense mechanisms against defective proteostasis. 

PMID- 25049228
TI  - The interaction between checkpoint kinase 1 (Chk1) and the minichromosome
      maintenance (MCM) complex is required for DNA damage-induced Chk1
      phosphorylation.
AB  - Chk1 is an essential mediator of the DNA damage response and cell cycle
      checkpoint. However, how exactly Chk1 transduces the checkpoint signaling is not
      fully understood. Here we report the identification of the heterohexamic
      minichromosome maintenance (MCM) complex that interacts with Chk1 by mass
      spectrometry. The interaction between Chk1 and the MCM complex was reduced by DNA
      damage treatment. We show that the MCM complex, at least partially, contributes
      to the chromatin association of Chk1, allowing for immediate phosphorylation of
      Chk1 by ataxia telangiectasia mutated and Rad3-related (ATR) in the presence of
      DNA damage. Further, phosphorylation of Chk1 at ATR sites reduces the interaction
      between Chk1 and the MCM complex, facilitating chromatin release of
      phosphorylated Chk1, a critical step in the initiation and amplification of cell
      cycle checkpoint. Together, these data provide novel insights into the activation
      of Chk1 in response to DNA damage. 

PMID- 25049229
TI  - Mapping the putative G protein-coupled receptor (GPCR) docking site on GPCR
      kinase 2: insights from intact cell phosphorylation and recruitment assays.
AB  - G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied
      receptors initiating the processes of desensitization and beta-arrestin-dependent
      signaling. Interaction of GRKs with activated receptors serves to stimulate their
      kinase activity. The extreme N-terminal helix (alphaN), the kinase small lobe,
      and the active site tether (AST) of the AGC kinase domain have previously been
      implicated in mediating the allosteric activation. Expanded mutagenesis of the
      alphaN and AST allowed us to further assess the role of these two regions in
      kinase activation and receptor phosphorylation in vitro and in intact cells. We
      also developed a bioluminescence resonance energy transfer-based assay to monitor
      the recruitment of GRK2 to activated alpha(2A)-adrenergic receptors
      (alpha(2A)ARs) in living cells. The bioluminescence resonance energy transfer
      signal exhibited a biphasic response to norepinephrine concentration, suggesting
      that GRK2 is recruited to Gbetagamma and alpha(2A)AR with EC50 values of 15 nM
      and 8 MUM, respectively. We show that mutations in alphaN (L4A, V7E, L8E, V11A,
      S12A, Y13A, and M17A) and AST (G475I, V477D, and I485A) regions impair or
      potentiate receptor phosphorylation and/or recruitment. We suggest that a surface
      of GRK2, including Leu(4), Val(7), Leu(8), Val(11), and Ser(12), directly
      interacts with receptors, whereas residues such as Asp(10), Tyr(13), Ala(16),
      Met(17), Gly(475), Val(477), and Ile(485) are more important for kinase domain
      closure and activation. Taken together with data on GRK1 and GRK6, our data
      suggest that all three GRK subfamilies make conserved interactions with G protein
      coupled receptors, but there may be unique interactions that influence
      selectivity.

PMID- 25049230
TI  - Homer2 protein regulates plasma membrane Ca2+-ATPase-mediated Ca2+ signaling in
      mouse parotid gland acinar cells.
AB  - Homer proteins are scaffold molecules with a domain structure consisting of an N
      terminal Ena/VASP homology 1 protein-binding domain and a C-terminal leucine
      zipper/coiled-coil domain. The Ena/VASP homology 1 domain recognizes proline-rich
      motifs and binds multiple Ca(2+)-signaling proteins, including G protein-coupled
      receptors, inositol 1,4,5-triphosphate receptors, ryanodine receptors, and
      transient receptor potential channels. However, their role in Ca(2+) signaling in
      nonexcitable cells is not well understood. In this study, we investigated the
      role of Homer2 on Ca(2+) signaling in parotid gland acinar cells using Homer2
      deficient (Homer2(-/-)) mice. Homer2 is localized at the apical pole in acinar
      cells. Deletion of Homer2 did not affect inositol 1,4,5-triphosphate receptor
      localization or channel activity and did not affect the expression and activity
      of sarco/endoplasmic reticulum Ca(2+)-ATPase pumps. In contrast, Homer2 deletion
      markedly increased expression of plasma membrane Ca(2+)-ATPase (PMCA) pumps, in
      particular PMCA4, at the apical pole. Accordingly, Homer2 deficiency increased
      Ca(2+) extrusion by acinar cells. These findings were supported by co
      immunoprecipitation of Homer2 and PMCA in wild-type parotid cells and transfected
      human embryonic kidney 293 (HEK293) cells. We identified a Homer-binding PPXXF
      like motif in the N terminus of PMCA that is required for interaction with
      Homer2. Mutation of the PPXXF-like motif did not affect the interaction of PMCA
      with Homer1 but inhibited its interaction with Homer2 and increased Ca(2+)
      clearance by PMCA. These findings reveal an important regulation of PMCA by
      Homer2 that has a central role on PMCA-mediated Ca(2+) signaling in parotid
      acinar cells. 

PMID- 25049231
TI  - DNA methylation-mediated repression of miR-941 enhances lysine (K)-specific
      demethylase 6B expression in hepatoma cells.
AB  - MicroRNAs (miRNAs) have been shown to play important roles in carcinogenesis.
      However, their underlying mechanisms of action in hepatocellular carcinoma (HCC)
      are poorly understood. Recent evidence suggests that epigenetic silencing of
      miRNAs through tumor suppression by CpG island hypermethylation may be a common
      hallmark of human tumors. Here, we demonstrated that miR-941 was significantly
      down-regulated in HCC tissues and cell lines and was generally hypermethylated in
      HCC. The overexpression of miR-941 suppressed in vitro cell proliferation,
      migration, and invasion and inhibited the metastasis of HCC cells in vivo.
      Furthermore, the histone demethylase KDM6B (lysine (K)-specific demethylase 6B)
      was identified as a direct target of miR-941 and was negatively regulated by miR
      941. The ectopic expression of KDM6B abrogated the phenotypic changes induced by
      miR-941 in HCC cells. We demonstrated that miR-941 and KDM6B regulated the
      epithelial-mesenchymal transition process and affected cell migratory/invasive
      properties. 

PMID- 25049232
TI  - Integrated stability and activity control of the Drosophila Rbf1 retinoblastoma
      protein.
AB  - The retinoblastoma (RB) family transcriptional corepressors regulate diverse
      cellular events including cell cycle, senescence, and differentiation. The
      activity and stability of these proteins are mediated by post-translational
      modifications; however, we lack a general understanding of how distinct
      modifications coordinately impact both of these properties. Previously, we showed
      that protein turnover and activity are tightly linked through an evolutionarily
      conserved C-terminal instability element (IE) in the Drosophila RB-related
      protein Rbf1; surprisingly, mutant proteins with enhanced stability were less,
      not more active. To better understand how activity and turnover are controlled in
      this model RB protein, we assessed the impact of Cyclin-Cdk kinase regulation on
      Rbf1. An evolutionarily conserved N-terminal threonine residue is required for
      Cyclin-Cdk response and showed a dominant impact on turnover and activity;
      however, specific residues in the C-terminal IE differentially impacted Rbf1
      activity and turnover, indicating an additional level of regulation. Strikingly,
      specific IE mutations that impaired turnover but not activity induced dramatic
      developmental phenotypes in the Drosophila eye. Mutation of the highly conserved
      Lys-774 residue induced hypermorphic phenotypes that mimicked the loss of
      phosphorylation control; mutation of the corresponding codon of the human RBL2
      gene has been reported in lung tumors. Our data support a model in which closely
      intermingled residues within the conserved IE govern protein turnover, presumably
      through interactions with E3 ligases, and protein activity via contacts with E2F
      transcription partners. Such functional relationships are likely to similarly
      impact mammalian RB family proteins, with important implications for development
      and disease. 

PMID- 25049233
TI  - Substrate specificities and conformational flexibility of 3-ketosteroid 9alpha
      hydroxylases.
AB  - KshA is the oxygenase component of 3-ketosteroid 9alpha-hydroxylase, a Rieske
      oxygenase involved in the bacterial degradation of steroids. Consistent with its
      role in bile acid catabolism, KshA1 from Rhodococcus rhodochrous DSM43269 had the
      highest apparent specificity (kcat/Km) for steroids with an isopropyl side chain
      at C17, such as 3-oxo-23,24-bisnorcholesta-1,4-diene-22-oate (1,4-BNC). By
      contrast, the KshA5 homolog had the highest apparent specificity for substrates
      with no C17 side chain (kcat/Km >10(5) s(-1) M(-1) for 4-estrendione, 5alpha
      androstandione, and testosterone). Unexpectedly, substrates such as 4-androstene
      3,17-dione (ADD) and 4-BNC displayed strong substrate inhibition (Ki S ~100 MUM).
      By comparison, the cholesterol-degrading KshAMtb from Mycobacterium tuberculosis
      had the highest specificity for CoA-thioesterified substrates. These
      specificities are consistent with differences in the catabolism of cholesterol
      and bile acids, respectively, in actinobacteria. X-ray crystallographic
      structures of the KshAMtb.ADD, KshA1.1,4-BNC-CoA, KshA5.ADD, and KshA5.1,4-BNC
      CoA complexes revealed that the enzymes have very similar steroid-binding pockets
      with the substrate's C17 oriented toward the active site opening. Comparisons
      suggest Tyr-245 and Phe-297 are determinants of KshA1 specificity. All enzymes
      have a flexible 16-residue "mouth loop," which in some structures completely
      occluded the substrate-binding pocket from the bulk solvent. Remarkably, the
      catalytic iron and alpha-helices harboring its ligands were displaced up to 4.4 A
      in the KshA5.substrate complexes as compared with substrate-free KshA, suggesting
      that Rieske oxygenases may have a dynamic nature similar to cytochrome P450.

PMID- 25049235
TI  - Construction of a wireless communication contact closure system for liquid
      chromatography with multiple parallel mass spectrometers and other detectors.
AB  - A contact closure system was constructed that uses two contact closure sender
      boards that communicate wirelessly to four contact closure receiver boards to
      distribute start signals from two or three liquid chromatographs to 14
      instruments, pumps, detectors, or other components. Default high, closed low, TTL
      logic (5-volt) start signals from two autosamplers are converted to simple
      contacts by powered relay boards that are then connected to two 16-channel
      wireless contact closure sender boards. The contact closure signals from the two
      sender boards are transmitted wirelessly to two pairs of eight-channel receiver
      boards (total of 32 contact signals) that distribute the start signal to 14
      switches that allow selection of which start signal is sent to which instrument,
      pump, or detector. The contact closure system is used for quadruple parallel mass
      spectrometry experiments in which four mass spectrometers, using three different
      atmospheric pressure ionization modes, plus a UV detector, an evaporative light
      scattering detector, a corona charged aerosol detector, and two syringe pumps
      supplying electrolyte, are all synchronized to start simultaneously. A wide
      variety of liquid chromatography-mass spectrometry experiments using multiple
      liquid chromatographs and mass spectrometers simultaneously, LCx/MSy, including
      column-switching experiments, can be reconfigured simply by toggling switches.

PMID- 25049234
TI  - Dual functions of the trans-2-enoyl-CoA reductase TER in the sphingosine 1
      phosphate metabolic pathway and in fatty acid elongation.
AB  - The sphingolipid metabolite sphingosine 1-phosphate (S1P) functions as a lipid
      mediator and as a key intermediate of the sole sphingolipid to
      glycerophospholipid metabolic pathway (S1P metabolic pathway). In this pathway,
      S1P is converted to palmitoyl-CoA through 4 reactions, then incorporated mainly
      into glycerophospholipids. Although most of the genes responsible for the S1P
      metabolic pathway have been identified, the gene encoding the trans-2-enoyl-CoA
      reductase, responsible for the saturation step (conversion of trans-2
      hexadecenoyl-CoA to palmitoyl-CoA) remains unidentified. In the present study, we
      show that TER is the missing gene in mammals using analyses involving yeast
      cells, deleting the TER homolog TSC13, and TER-knockdown HeLa cells. TER is known
      to be involved in the production of very long-chain fatty acids (VLCFAs). A
      significant proportion of the saturated and monounsaturated VLCFAs are used for
      sphingolipid synthesis. Therefore, TER is involved in both the production of
      VLCFAs used in the fatty acid moiety of sphingolipids as well as in the
      degradation of the sphingosine moiety of sphingolipids via S1P. 

PMID- 25049236
TI  - Ultrasound attenuation computed tomography assessment of PAGAT gel dose.
AB  - Ultrasound has been previously investigated as an alternative readout method for
      irradiated polymer gel dosimeters, with authors reporting varying dose responses.
      We extend previous work utilizing a new computed tomography ultrasound scanner
      comprising of two identical 5 MHz, 128-element linear-array ultrasound
      transducers, co-axially aligned and submerged in water as a coupling agent, with
      rotational of the gel dosimeter between the transducers facilitated by a robotic
      arm. We have investigated the dose-dependence of both ultrasound bulk attenuation
      and broadband ultrasound attenuation (BUA) for the PAGAT gel dosimeter. The
      ultrasound bulk attenuation dose sensitivity was found to be 1.46  +/-  0.04 dB
      m( -1) Gy( -1), being in agreement with previously published results for PAG and
      MAGIC gels. BUA was also found to be dose dependent and was measured to be 0.024 
      +/-  0.003 dB MHz( -1) Gy( -1); the advantage of BUA being its insensitivity to
      frequency-independent attenuation mechanisms including reflection and refraction,
      thereby minimizing image reconstruction artefacts. 

PMID- 25049237
TI  - Protein engineering study of beta-mannosidase to set up a potential chemically
      efficient biocatalyst.
AB  - This study is focused on the analysis and mutagenesis of beta-mannosidase from
      Bacteroides thetaiotaomicron with the aim of broadening its substrate specificity
      to 2-acetamido-2-deoxy-beta-d-mannopyranosyl (beta-ManNAc) derivatives. Various
      conformations ((4)C1, (4)H5 and (1)S5) of native and modified ligands were docked
      to the binding site of the protein to determine the most suitable conformation of
      sugars for further hydrolysis. Key amino acid residues were mutated in silico
      focusing on stabilizing the acetamido group of beta-ManNAc as well as forming the
      oxazoline intermediate needed for hydrolysis. The results of large set of 5 ns
      molecular dynamic simulations showed that the majority of the active site
      residues are involved in substrate interaction and do not exhibit a higher
      flexibility except for Asn178. Mutations of Asn178 to alanine and Asp199 to
      serine could lead to a stabilization of the acetamido group in the binding site.
      So far, in vitro mutagenesis and the screen of a large variety of biological
      sources were unable to extend beta-mannosidase's activity to include beta-ManNAc
      derivatives. 

PMID- 25049238
TI  - Engineering the carbohydrate-binding site of Epa1p from Candida glabrata:
      generation of adhesin mutants with different carbohydrate specificity.
AB  - The N-terminal domain of the Epa1p adhesin from Candida glabrata (N-Epa1p) is a
      calcium-dependent lectin, which confers the opportunistic yeast the ability to
      adhere to human epithelial cells. This lectin domain is able to interact with
      galactosides and, more precisely, with glycan molecules containing the Galbeta
      1,3-GalNAc disaccharide, also known as the T-antigen. Based on the
      crystallographic structure of the N-Epa1p domain and the role of the variable
      loop CBL2 in glycan binding, saturation mutagenesis on some residues of the CBL2
      loop was used to increase the binding affinity of N-Epa1p for fibronectin, which
      was selected as a model of a human glycoprotein. Two adhesin mutants, E227A and
      Y228W, with improved binding features were obtained. More importantly, a glycan
      array screening revealed that single-point mutations in the CBL2 could produce
      significant changes in the carbohydrate specificity of the protein. In
      particular, lectin molecules were generated with a high affinity for sulfated
      glycans, which may find an application as molecular probes for the identification
      of 6-sulfogalactose containing glycans and glycoconjugates. 

PMID- 25049239
TI  - Toward a robust computational screening strategy for identifying
      glycosaminoglycan sequences that display high specificity for target proteins.
AB  - Glycosaminoglycans (GAGs) interact with many proteins to regulate processes such
      as hemostasis, cell adhesion, growth and differentiation and viral infection.
      Yet, majority of these interactions remain poorly understood at a molecular
      level. A major reason for this state is the phenomenal structural diversity of
      GAGs, which has precluded analysis of specificity of their interactions. We had
      earlier presented a computational protocol for predicting "high-specificity" GAG
      sequences based on combinatorial virtual library screening (CVLS) technology. In
      this work, we expand the robustness of this technology through rigorous studies
      of parameters affecting GAG recognition of proteins, especially antithrombin and
      thrombin. The CVLS approach involves automated construction of a virtual library
      of all possible oligosaccharide sequences (di- to octasaccharide) followed by a
      two-step selection strategy consisting of "affinity" (GOLD score) and
      "specificity" (consistency of binding) filters. We find that "specificity"
      features are optimally evaluated using 100 genetic algorithm experiments, 100,000
      evolutions and variable docking radius from 10 A (disaccharide) to 14 A
      (hexasaccharide). The results highlight critical interactions in H/HS
      oligosaccharides that govern specificity. Application of CVLS technology to the
      antithrombin-heparin system indicates that the minimal "specificity" element is
      the GlcAp(1 -> 4)GlcNp2S3S disaccharide of heparin. The CVLS technology affords a
      simple, intuitive framework for the design of longer GAG sequences that can
      exhibit high "specificity" without resorting to exhaustive screening of millions
      of theoretical sequences. 

PMID- 25049240
TI  - Synergy of silver nanoparticles and aztreonam against Pseudomonas aeruginosa PAO1
      biofilms.
AB  - Pathogenic bacterial biofilms, such as those found in the lungs of patients with
      cystic fibrosis (CF), exhibit increased antimicrobial resistance, due in part to
      the inherent architecture of the biofilm community. The protection provided by
      the biofilm limits antimicrobial dispersion and penetration and reduces the
      efficacy of antibiotics that normally inhibit planktonic cell growth. Thus,
      alternative antimicrobial strategies are required to combat persistent
      infections. The antimicrobial properties of silver have been known for decades,
      but silver and silver-containing compounds have recently seen renewed interest as
      antimicrobial agents for treating bacterial infections. The goal of this study
      was to assess the efficacy of citrate-capped silver nanoparticles (AgNPs) of
      various sizes, alone and in combination with the monobactam antibiotic aztreonam,
      to inhibit Pseudomonas aeruginosa PAO1 biofilms. Among the different sizes of
      AgNPs examined, 10-nm nanoparticles were most effective in inhibiting the
      recovery of P. aeruginosa biofilm cultures and showed synergy of inhibition when
      combined with sub-MIC levels of aztreonam. Visualization of biofilms treated with
      combinations of 10-nm AgNPs and aztreonam indicated that the synergistic
      bactericidal effects are likely caused by better penetration of the small AgNPs
      into the biofilm matrix, which enhances the deleterious effects of aztreonam
      against the cell envelope of P. aeruginosa within the biofilms. These data
      suggest that small AgNPs synergistically enhance the antimicrobial effects of
      aztreonam against P. aeruginosa in vitro, and they reveal a potential role for
      combinations of small AgNPs and antibiotics in treating patients with chronic
      infections. 

PMID- 25049241
TI  - Pantothenic acid biosynthesis in the parasite Toxoplasma gondii: a target for
      chemotherapy.
AB  - Toxoplasma gondii is a major food pathogen and neglected parasitic infection that
      causes eye disease, birth defects, and fetal abortion and plays a role as an
      opportunistic infection in AIDS. In this study, we investigated pantothenic acid
      (vitamin B5) biosynthesis in T. gondii. Genes encoding the full repertoire of
      enzymes for pantothenate synthesis and subsequent metabolism to coenzyme A were
      identified and are expressed in T. gondii. A panel of inhibitors developed to
      target Mycobacterium tuberculosis pantothenate synthetase were tested and found
      to exhibit a range of values for inhibition of T. gondii growth. Two inhibitors
      exhibited lower effective concentrations than the currently used toxoplasmosis
      drug pyrimethamine. The inhibition was specific for the pantothenate pathway, as
      the effect of the pantothenate synthetase inhibitors was abrogated by
      supplementation with pantothenate. Hence, T. gondii encodes and expresses the
      enzymes for pantothenate synthesis, and this pathway is essential for parasite
      growth. These promising findings increase our understanding of growth and
      metabolism in this important parasite and highlight pantothenate synthetase as a
      new drug target. 

PMID- 25049242
TI  - Effect of coadministered fat on the tolerability, safety, and pharmacokinetic
      properties of dihydroartemisinin-piperaquine in Papua New Guinean children with
      uncomplicated malaria.
AB  - Coadministration of dihydroartemisinin-piperaquine (DHA-PQ) with fat may improve
      bioavailability and antimalarial efficacy, but it might also increase toxicity.
      There have been no studies of these potential effects in the pediatric age group.
      The tolerability, safety, efficacy, and pharmacokinetics of DHA-PQ administered
      with or without 8.5 g fat were investigated in 30 Papua New Guinean children aged
      5 to 10 years diagnosed with uncomplicated falciparum malaria. Three daily
      2.5:11.5-mg-base/kg doses were given with water (n = 14, group A) or milk (n =
      16, group B), with regular clinical/laboratory assessment and blood sampling over
      42 days. Plasma PQ was assayed by high-performance liquid chromatography with UV
      detection, and DHA was assayed using liquid chromatography-mass spectrometry.
      Compartmental pharmacokinetic models for PQ and DHA were developed using a
      population-based approach. DHA-PQ was generally well tolerated, and initial fever
      and parasite clearance were prompt. There were no differences in the areas under
      the concentration-time curve (AUC0-infinity) for PQ (median, 41,906 versus 36,752
      MUg . h/liter in groups A and B, respectively; P = 0.24) or DHA (4,047 versus
      4,190 MUg . h/liter; P = 0.67). There were also no significant between-group
      differences in prolongation of the corrected electrocardiographic QT interval
      (QTc) initially during follow-up, but the QTc tended to be higher in group B
      children at 24 h (mean +/- standard deviation [SD], 15 +/- 10 versus 6 +/- 15
      ms(0.5) in group A, P = 0.067) and 168 h (10 +/- 18 versus 1 +/- 23 ms(0.5), P =
      0.24) when plasma PQ concentrations were relatively low. A small amount of fat
      does not change the bioavailability of DHA-PQ in children, but a delayed
      persistent effect on ventricular repolarization cannot be excluded. 

PMID- 25049243
TI  - Simple and rapid method to determine antimycobacterial potency of compounds by
      using autoluminescent Mycobacterium tuberculosis.
AB  - A major obstacle in the process of discovery of drugs against Mycobacterium
      tuberculosis is its extremely slow growth rate and long generation time (~20 to
      24 h). Consequently, determination of MICs and minimum bactericidal
      concentrations (MBCs) of potential drug candidates using current methods requires
      7 days (resazurin-based MIC assay [REMA]) and 1 month (CFU enumeration),
      respectively. We employed a synthetic luciferase operon optimized for expression
      in high-GC-content bacteria and adapted it for use in mycobacteria. Using
      luminescence-based readouts, we were able to determine the MICs and bactericidal
      activities of approved tuberculosis (TB) drugs, which correlated well with
      currently used methods. Although luminescence-based readouts have been used
      previously to determine the MICs and bactericidal activities of approved TB
      drugs, in this study we adapted this assay to carry out a pilot screen using a
      library of 1,114 compounds belonging to diverse chemical scaffolds. We found that
      MICs derived from a 3-day luminescence assay matched well with REMA-based MIC
      values. To determine the bactericidal potencies of compounds, a 1:10 dilution of
      the cultures from the MIC plate was carried out on day 7, and the bactericidal
      concentrations determined based on time to positivity in 2 weeks were found to be
      comparable with MBC values determined by the conventional CFU approach. Thus, the
      luminescent mycobacterium-based approach not only is very simple and inexpensive
      but also allowed us to generate the information in half the time required by
      conventional methods. 

PMID- 25049244
TI  - Drug target identification using a trypanosome overexpression library.
AB  - Elucidation of molecular targets is very important for lead optimization during
      the drug development process. We describe a direct method to find targets of
      antitrypanosomal compounds against Trypanosoma brucei using a trypanosome
      overexpression library. As proof of concept, we treated the library with
      difluoromethylornithine and DDD85646 and identified their respective targets,
      ornithine decarboxylase and N-myristoyltransferase. The overexpression library
      could be a useful tool to study the modes of action of novel antitrypanosomal
      drug candidates. 

PMID- 25049245
TI  - Experimental therapy with azoles against Candida guilliermondii.
AB  - We evaluated the in vitro killing activity of voriconazole (VRC) and posaconazole
      (PSC) against two clinical isolates of Candida guilliermondii. The two drugs
      showed fungistatic activity against both isolates and were effective in reducing
      kidney fungal burden in a neutropenic murine model of disseminated candidiasis in
      infected mice. PSC was significantly more effective than VRC against one of the
      strains. The serum levels of PSC and VRC were above the corresponding MICs for
      these isolates. 

PMID- 25049246
TI  - Transient and sustained bacterial adaptation following repeated sublethal
      exposure to microbicides and a novel human antimicrobial peptide.
AB  - Microbicides (biocides) play an important role in the prevention and treatment of
      infections. While there is currently little evidence for in-use treatment
      failures attributable to acquired reductions in microbicide susceptibility, the
      susceptibility of some bacteria can be reduced by sublethal laboratory exposure
      to certain agents. In this investigation, a range of environmental bacterial
      isolates (11 genera, 18 species) were repeatedly exposed to four microbicides
      (cetrimide, chlorhexidine, polyhexamethylene biguanide [PHMB], and triclosan) and
      a cationic apolipoprotein E-derived antimicrobial peptide (apoEdpL-W) using a
      previously validated exposure system. Susceptibilities (MICs and minimum
      bactericidal concentrations [MBCs]) were determined before and after 10 passages
      (P10) in the presence of an antimicrobial and then after a further 10 passages
      without an antimicrobial to determine the stability of any adaptations. Bacteria
      exhibiting >4-fold increases in MBCs were further examined for alterations in
      biofilm-forming ability. Following microbicide exposure, >=4-fold decreases in
      susceptibility (MIC or MBC) occurred for cetrimide (5/18 bacteria), apoEdpL-W
      (7/18), chlorhexidine (8/18), PHMB (8/18), and triclosan (11/18). Of the 34 >=4
      fold increases in the MICs, 15 were fully reversible, 13 were partially
      reversible, and 6 were nonreversible. Of the 26 >=4-fold increases in the MBCs, 7
      were fully reversible, 14 were partially reversible, and 5 were nonreversible.
      Significant decreases in biofilm formation in P10 strains occurred for apoEdpL-W
      (1/18 bacteria), chlorhexidine (1/18), and triclosan (2/18), while significant
      increases occurred for apoEdpL-W (1/18), triclosan (1/18), and chlorhexidine
      (2/18). These data indicate that the stability of induced changes in microbicide
      susceptibility varies but may be sustained for some combinations of a bacterium
      and a microbicide. 

PMID- 25049247
TI  - Phase 1b study of new posaconazole tablet for prevention of invasive fungal
      infections in high-risk patients with neutropenia.
AB  - Posaconazole tablets, a new oral formulation of posaconazole, can be effective
      when given as antifungal prophylaxis to neutropenic patients at high risk for
      invasive fungal infection (e.g., those with acute myelogenous leukemia or
      myelodysplastic syndrome). Such effectiveness might be specifically important to
      patients with poor oral intake because of nausea, vomiting, or chemotherapy
      associated mucositis. This was a prospective, global study in high-risk patients
      to characterize the pharmacokinetics and safety profile of posaconazole tablets
      and to identify the dose of posaconazole tablets that would provide exposure
      within a predefined range of exposures (steady-state average concentration [area
      under the concentration-time curve/24 h] of >=500 ng/ml and <=2,500 ng/ml in >90%
      of patients). The study evaluated two sequential dosing cohorts: 200 mg
      posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34)
      (both cohorts had a twice-daily loading dose on day 1) taken without regard to
      food intake during the neutropenic period for <=28 days. The exposure target was
      reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200
      mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg
      posaconazole once daily; 300 mg posaconazole once daily achieved the desired
      exposure target. Posaconazole tablets were generally well tolerated in high-risk
      neutropenic patients. (This study has been registered at ClinicalTrials.gov under
      registration no. NCT01777763.). 

PMID- 25049248
TI  - Mutations in mmpL and in the cell wall stress stimulon contribute to resistance
      to oxadiazole antibiotics in methicillin-resistant Staphylococcus aureus.
AB  - Staphylococcus aureus is a leading cause of hospital- and community-acquired
      infections, which exhibit broad resistance to various antibiotics. We recently
      disclosed the discovery of the oxadiazole class of antibiotics, which has in
      vitro and in vivo activities against methicillin-resistant S. aureus (MRSA). We
      report herein that MmpL, a putative member of the resistance, nodulation, and
      cell division (RND) family of proteins, contributes to oxadiazole resistance in
      the S. aureus strain COL. Through serial passages, we generated two S. aureus COL
      variants that showed diminished susceptibilities to an oxadiazole antibiotic. The
      MICs for the oxadiazole against one strain (designated S. aureus COL(I))
      increased reproducibly 2-fold (to 4 MUg/ml), while against the other strain (S.
      aureus COL(R)), they increased >4-fold (to >8 MUg/ml, the limit of solubility).
      The COL(R) strain was derived from the COL(I) strain. Whole-genome sequencing
      revealed 31 mutations in S. aureus COL(R), of which 29 were shared with COL(I).
      Consistent with our previous finding that oxadiazole antibiotics inhibit cell
      wall biosynthesis, we found 13 mutations that occurred either in structural genes
      or in promoters of the genes of the cell wall stress stimulon. Two unique
      mutations in S. aureus COL(R) were substitutions in two genes that encode the
      putative thioredoxin (SACOL1794) and MmpL (SACOL2566). A role for mmpL in
      resistance to oxadiazoles was discerned from gene deletion and complementation
      experiments. To our knowledge, this is the first report that a cell wall-acting
      antibiotic selects for mutations in the cell wall stress stimulon and the first
      to implicate MmpL in resistance to antibiotics in S. aureus. 

PMID- 25049249
TI  - Chloroquine remains effective for treating Plasmodium vivax malaria in Pursat
      province, Western Cambodia.
AB  - Chloroquine (CQ) is used to treat Plasmodium vivax malaria in areas where CQ
      resistance has not been reported. The use of artemisinin (ART)-based combination
      therapies (ACTs) to treat CQ-sensitive P. vivax infections is effective and
      convenient but may promote the emergence and worsening of ART resistance in
      sympatric Plasmodium falciparum populations. Here, we show that CQ effectively
      treats P. vivax malaria in Pursat Province, western Cambodia, where ART-resistant
      P. falciparum is highly prevalent and spreading. (This study has been registered
      at ClinicalTrials.gov under registration no. NCT00663546.). 

PMID- 25049250
TI  - First identification of a chromosomally located penicillinase gene in Kingella
      kingae species isolated in continental Europe.
AB  - Kingella kingae is the major pathogen causing osteoarticular infections (OAI) in
      young children in numerous countries. Plasmid-borne TEM-1 penicillinase
      production has been sporadically detected in a few countries but not in
      continental Europe, despite a high prevalence of K. kingae infections. We
      describe here for the first time a K. kingae beta-lactamase-producing strain in
      continental Europe and demonstrate the novel chromosomal location of the blaTEM-1
      gene in K. kingae species. 

PMID- 25049251
TI  - Time-kill assay and Etest evaluation for synergy with polymyxin B and fluconazole
      against Candida glabrata.
AB  - Fluconazole-resistant Candida glabrata is an emerging pathogen that causes
      fungemia. Polymyxin B, a last-resort antibiotic used to treat multidrug-resistant
      Gram-negative bacterial infections, has been found to possess in vitro fungicidal
      activity and showed synergy with fluconazole against a single strain of C.
      glabrata. Since both agents may be used simultaneously in intensive care unit
      (ICU) patients, this study was performed to test for possible synergy of this
      combination against 35 C. glabrata blood isolates, using 2 methods: a time-kill
      assay and an experimental MIC-MIC Etest method. Thirty-five genetically unique C.
      glabrata bloodstream isolates were collected from 2009 to 2011, identified using
      an API 20C system, and genotyped by repetitive sequence-based PCR (rep-PCR). MICs
      were determined by Etest and broth microdilution methods. Synergy testing was
      performed using a modified bacterial Etest synergy method and time-kill assay,
      with final results read at 24 h. The Etest method showed synergy against 19/35
      (54%) isolates; the time-kill assay showed synergy against 21/35 (60%) isolates.
      Isolates not showing drug synergy had an indifferent status. Concordance between
      methods was 60%. In vitro synergy of polymyxin B and fluconazole against the
      majority of C. glabrata isolates was demonstrated by both methods. The bacterial
      Etest synergy method adapted well when used with C. glabrata. Etest was easier to
      perform than time-kill assay and may be found to be an acceptable alternative to
      time-kill assay with antifungals. 

PMID- 25049252
TI  - Ex vivo activity of endoperoxide antimalarials, including artemisone and
      arterolane, against multidrug-resistant Plasmodium falciparum isolates from
      Cambodia.
AB  - Novel synthetic endoperoxides are being evaluated as new components of
      artemisinin combination therapies (ACTs) to treat artemisinin-resistant
      Plasmodium falciparum malaria. We conducted blinded ex vivo activity testing of
      fully synthetic (OZ78 and OZ277) and semisynthetic (artemisone, artemiside,
      artesunate, and dihydroartemisinin) endoperoxides in the histidine-rich protein 2
      enzyme-linked immunosorbent assay against 200 P. falciparum isolates from areas
      of artemisinin-resistant malaria in western and northern Cambodia in 2009 and
      2010. The order of potency and geometric mean (GM) 50% inhibitory concentrations
      (IC50s) were as follows: artemisone (2.40 nM) > artesunate (8.49 nM) >
      dihydroartemisinin (11.26 nM) > artemiside (15.28 nM) > OZ277 (31.25 nM) > OZ78
      (755.27 nM). Ex vivo activities of test endoperoxides positively correlated with
      dihydroartemisinin and artesunate. The isolates were over 2-fold less susceptible
      to dihydroartemisinin than the artemisinin-sensitive P. falciparum W2 clone and
      showed sensitivity comparable to those with test endoperoxides and artesunate,
      with isolate/W2 IC50 susceptibility ratios of <2.0. All isolates had P.
      falciparum chloroquine resistance transporter mutations, with negative
      correlations in sensitivity to endoperoxides and chloroquine. The activities of
      endoperoxides (artesunate, dihydroartemisinin, OZ277, and artemisone)
      significantly correlated with that of the ACT partner drug, mefloquine. Isolates
      had mutations associated with clinical resistance to mefloquine, with 35%
      prevalence of P. falciparum multidrug resistance gene 1 (pfmdr1) amplification
      and 84.5% occurrence of the pfmdr1 Y184F mutation. GM IC50s for mefloquine,
      lumefantrine, and endoperoxides (artesunate, dihydroartemisinin, OZ277, OZ78, and
      artemisone) correlated with pfmdr1 copy number. Given that current ACTs are
      failing potentially from reduced sensitivity to artemisinins and partner drugs,
      newly identified mutations associated with artemisinin resistance reported in the
      literature and pfmdr1 mutations should be examined for their combined
      contributions to emerging ACT resistance. 

PMID- 25049253
TI  - In vitro analysis of finasteride activity against Candida albicans urinary
      biofilm formation and filamentation.
AB  - Candida albicans is the 3rd most common cause of catheter-associated urinary
      tract infections, with a strong propensity to form drug-resistant catheter
      related biofilms. Due to the limited efficacy of available antifungals against
      biofilms, drug repurposing has been investigated in order to identify novel
      agents with activities against fungal biofilms. Finasteride is a 5-alpha
      reductase inhibitor commonly used for the treatment of benign prostatic
      hyperplasia, with activity against human type II and III isoenzymes. We analyzed
      the Candida Genome Database and identified a C. albicans homolog of type III 5
      alpha-reductase, Dfg10p, which shares 27% sequence identity and 41% similarity to
      the human type III 5-alpha-reductase. Thus, we investigated finasteride for
      activity against C. albicans urinary biofilms, alone and in combination with
      amphotericin B or fluconazole. Finasteride alone was highly effective in the
      prevention of C. albicans biofilm formation at doses of >=16 mg/liter and the
      treatment of preformed biofilms at doses of >=128 mg/liter. In biofilm
      checkerboard analyses, finasteride exhibited synergistic activity in the
      prevention of biofilm formation in a combination of 4 mg/liter finasteride with 2
      mg/liter fluconazole. Finasteride inhibited filamentation, thus suggesting a
      potential mechanism of action. These results indicate that finasteride alone is
      highly active in the prevention of C. albicans urinary biofilms in vitro and has
      synergistic activity in combination with fluconazole. Further investigation of
      the clinical utility of finasteride in the prevention of urinary candidiasis is
      warranted. 

PMID- 25049254
TI  - Deletion mutations conferring substrate spectrum extension in the class A beta
      lactamase.
AB  - We describe four new deletion mutations in a class A beta-lactamase PenA in
      Burkholderia thailandensis, each conferring an extended substrate spectrum.
      Single-amino-acid deletions T171del, I173del, and P174del and a two-amino-acid
      deletion, R165_T167delinsP, occurred in the omega loop, increasing the
      flexibility of the binding cavity. This rare collection of mutations has
      significance, allowing exploration of the diverse evolutionary trajectories of
      beta-lactamases and as potential future mutations conferring high-level
      ceftazidime resistance on isolates from clinical settings, compared with amino
      acid substitution mutations. 

PMID- 25049255
TI  - Antibiotic pressure is a major risk factor for rectal colonization by multidrug
      resistant Pseudomonas aeruginosa in critically ill patients.
AB  - The intestinal reservoir is central to the epidemiology of Pseudomonas
      aeruginosa, but the dynamics of intestinal colonization by different phenotypes
      have been poorly described. To determine the impact of antimicrobial exposure on
      intestinal colonization by multidrug-resistant (MDR) and extensively drug
      resistant (XDR) P. aeruginosa, we screened intensive care unit (ICU) patients for
      rectal colonization on admission and at weekly intervals. During an 18-month
      study period, 414 ICU patients were enrolled, of whom 179 (43%) were colonized;
      112 (63%) of these were identified at ICU admission and 67 (37%) during their ICU
      stay. At 10 days after ICU admission, the probabilities of carriage were 44%,
      24%, and 24% for non-MDR, MDR-non-XDR, and XDR P. aeruginosa strains,
      respectively (log rank, 0.02). Pulsed-field gel electrophoresis showed 10 pairs
      of non-MDR P. aeruginosa and subsequent MDR-non-XDR strains isolated from the
      same patients to be clonally identical and another 13 pairs (8 MDR-non-XDR and 5
      XDR) to be unrelated. There was one specific clone between the 8 MDR-non-XDR
      strains and an identical genotype in the 5 XDR isolates. The Cox regression
      analysis identified MDR P. aeruginosa acquisition as associated with the
      underlying disease severity (adjusted hazard ratio [aHR], 1.97; 95% confidence
      interval [CI], 1.22 to 3.18; P = 0.006) and prior use of fluoroquinolones (aHR,
      1.02; 95% CI, 1.00 to 1.04; P = 0.039), group 2 carbapenems (aHR, 1.03; 95% CI,
      1.00 to 1.07; P = 0.041), and ertapenem (aHR, 1.08; 95% CI, 1.02 to 1.14; P =
      0.004). The epidemiology of MDR P. aeruginosa is complex, and different clusters
      may coexist. Interestingly, ertapenem was found to be associated with the
      emergence of MDR isolates. 

PMID- 25049256
TI  - Transmission potential of antimony-resistant leishmania field isolates.
AB  - We studied the development of antimony-resistant Leishmania infantum in natural
      vectors Lutzomyia longipalpis and Phlebotomus perniciosus to ascertain the risk
      of parasite transmission by sand flies. All three resistant strains produced
      fully mature late-stage infections in sand flies; moreover, the resistant
      phenotype was maintained after the passage through the vector. These results
      highlight the risk of circulation of resistant Leishmania strains and question
      the use of human drugs for treatment of dogs as Leishmania reservoirs. 

PMID- 25049257
TI  - Statins increase rifampin mycobactericidal effect.
AB  - Mycobacterium leprae and Mycobacterium tuberculosis antimicrobial resistance has
      been followed with great concern during the last years, while the need for new
      drugs able to control leprosy and tuberculosis, mainly due to extensively drug
      resistant tuberculosis (XDR-TB), is pressing. Our group recently showed that M.
      leprae is able to induce lipid body biogenesis and cholesterol accumulation in
      macrophages and Schwann cells, facilitating its viability and replication.
      Considering these previous results, we investigated the efficacies of two statins
      on the intracellular viability of mycobacteria within the macrophage, as well as
      the effect of atorvastatin on M. leprae infections in BALB/c mice. We observed
      that intracellular mycobacteria viability decreased markedly after incubation
      with both statins, but atorvastatin showed the best inhibitory effect when
      combined with rifampin. Using Shepard's model, we observed with atorvastatin an
      efficacy in controlling M. leprae and inflammatory infiltrate in the BALB/c
      footpad, in a serum cholesterol level-dependent way. We conclude that statins
      contribute to macrophage-bactericidal activity against Mycobacterium bovis, M.
      leprae, and M. tuberculosis. It is likely that the association of statins with
      the actual multidrug therapy effectively reduces mycobacterial viability and
      tissue lesion in leprosy and tuberculosis patients, although epidemiological
      studies are still needed for confirmation. 

PMID- 25049258
TI  - Bacterial drug tolerance under clinical conditions is governed by anaerobic
      adaptation but not anaerobic respiration.
AB  - Noninherited antibiotic resistance is a phenomenon whereby a subpopulation of
      genetically identical bacteria displays phenotypic tolerance to antibiotics. We
      show here that compared to Escherichia coli, the clinically relevant genus
      Burkholderia displays much higher levels of cells that tolerate ceftazidime. By
      measuring the dynamics of the formation of drug-tolerant cells under conditions
      that mimic in vivo infections, we show that in Burkholderia bacteria, oxygen
      levels affect the formation of these cells. The drug-tolerant cells are
      characterized by an anaerobic metabolic signature and can be eliminated by
      oxygenating the system or adding nitrate. The transcriptome profile suggests that
      these cells are not dormant persister cells and are likely to be drug tolerant as
      a consequence of the upregulation of anaerobic nitrate respiration, efflux pumps,
      beta-lactamases, and stress response proteins. These findings have important
      implications for the treatment of chronic bacterial infections and the
      methodologies and conditions that are used to study drug-tolerant and persister
      cells in vitro. 

PMID- 25049260
TI  - Structural magnetic resonance imaging markers of susceptibility and transition to
      schizophrenia: a review of familial and clinical high risk population studies.
AB  - There is a growing consensus that a symptomatology as complex and heterogeneous
      as schizophrenia is likely to be produced by widespread perturbations of brain
      structure, as opposed to isolated deficits in specific brain regions. Structural
      brain-imaging studies have shown that several features of the brain, such as grey
      matter, white matter integrity and the morphology of the cortex differ in
      individuals at high risk of the disorder compared to controls, but to a lesser
      extent than in patients, suggesting that structural abnormalities may form
      markers of vulnerability to the disorder. Research has had some success in
      delineating abnormalities specific to those individuals that transition to
      psychosis, compared to those at high risk that do not, suggesting that a general
      risk for the disorder can be distinguished from alterations specific to frank
      psychosis. In this paper, we review cross-sectional and longitudinal studies of
      individuals at familial or clinical high risk of the disorder. We conclude that
      the search for reliable markers of schizophrenia is likely to be enhanced by
      methods which amalgamate structural neuroimaging data into a coherent framework
      that takes into account the widespread distribution of brain alterations, and
      relates this to leading hypotheses of schizophrenia. 

PMID- 25049261
TI  - Re-examining the role of benzodiazepines in the treatment of schizophrenia: a
      systematic review.
AB  - BACKGROUND: Benzodiazepine prescribing for schizophrenia occurs in clinical
      practice and antipsychotic trials. This review examined the clinical outcomes for
      benzodiazepines in schizophrenia. METHOD: A systematic search identified
      randomised controlled trials that evaluated benzodiazepines in comparison with
      placebo or antipsychotics, and also as adjuncts to antipsychotics. Relevant
      clinical outcome data was extracted. RESULTS: Twenty six studies were included
      with some reporting multiple comparisons. Seven short-term studies compared
      benzodiazepines with placebo: benzodiazepine superiority was found in two out of
      five studies for global improvements and two out of four studies for
      psychiatric/behavioural outcomes. Eleven studies compared benzodiazepines with
      first-generation antipsychotics (FGAs): four out of nine studies (including two
      long-term studies) reported greater global improvements for antipsychotics; four
      out of five studies showed no treatment differences for psychiatric/behavioural
      outcomes. Fourteen studies compared benzodiazepines (as adjunct to
      antipsychotics) vs antipsychotics alone (mostly FGAs); benzodiazepine superiority
      was found for global improvement in one out of eight studies and inferiority in
      two out of eight short-term studies whereas superiority was found for
      psychiatric/behavioural outcomes in three out of 12 short-term studies and
      inferiority in three out of 12 studies. CONCLUSION: Benzodiazepine superiority
      over placebo was found for global, psychiatric and behavioural outcomes, but
      inferiority to antipsychotics on longer-term global outcomes. Conflicting
      evidence exists regarding the addition of benzodiazepines to antipsychotics; thus
      the use of benzodiazepines in clinical practice and antipsychotic trials should
      be limited.

PMID- 25049259
TI  - Repurposing the open access malaria box to discover potent inhibitors of
      Toxoplasma gondii and Entamoeba histolytica.
AB  - Toxoplasmosis and amebiasis are important public health concerns worldwide. The
      drugs currently available to control these diseases have proven limitations.
      Therefore, innovative approaches should be adopted to identify and develop new
      leads from novel scaffolds exhibiting novel modes of action. In this paper, we
      describe results from the screening of compounds in the Medicines for Malaria
      Venture (MMV) open access Malaria Box in a search for new anti-Toxoplasma and
      anti-Entamoeba agents. Standard in vitro phenotypic screening procedures were
      adopted to assess their biological activities. Seven anti-Toxoplasma compounds
      with a 50% inhibitory concentration (IC50) of <5 MUM and selectivity indexes (SI)
      of >6 were identified. The most interesting compound was MMV007791, a piperazine
      acetamide, which has an IC50 of 0.19 MUM and a selectivity index of >157. Also,
      we identified two compounds, MMV666600 and MMV006861, with modest activities
      against Entamoeba histolytica, with IC50s of 10.66 MUM and 15.58 MUM,
      respectively. The anti-Toxoplasma compounds identified in this study belong to
      scaffold types different from those of currently used drugs, underscoring their
      novelty and potential as starting points for the development of new
      antitoxoplasmosis drugs with novel modes of action. 

PMID- 25049262
TI  - Appendicular skeletal muscle in hospitalised hip-fracture patients: development
      and cross-validation of anthropometric prediction equations against dual-energy X
      ray absorptiometry.
AB  - BACKGROUND: accurate and practical assessment methods for assessing appendicular
      skeletal muscle (ASM) is of clinical importance for the diagnosis of geriatric
      syndromes associated with skeletal muscle wasting. OBJECTIVES: the purpose of
      this study was to develop and cross-validate novel anthropometric prediction
      equations for the estimate of ASM in older adults post-surgical fixation for hip
      fracture, using dual-energy X-ray absorptiometry (DEXA) as the criterion measure.
      SUBJECTS: community-dwelling older adults (aged >=65 years) recently hospitalised
      for hip fracture. SETTING: participants were recruited from hospital in the acute
      phase of recovery. DESIGN: validation measurement study. MEASUREMENTS: a total of
      79 hip fracture patients were involved in the development of the regression
      models (MD group). A further 64 hip fracture patients also recruited in the early
      phase of recovery were used in the cross-validation of the regression models (CV
      group). Multiple linear regression analyses were undertaken in the MD group to
      identify the best performing prediction models. The linear coefficient of
      determination (R(2)) in addition to the standard error of the estimate (SEE) were
      calculated to determine the best performing model. Agreement between estimated
      ASM and ASMDEXA in the CV group was assessed using paired t-tests with the 95%
      limits of agreement (LOA) assessed using Bland-Altman analyses. RESULTS: the mean
      age of all the participants was 82.1 +/- 7.3 years. The best two prediction
      models are presented as follows: ASMPRED-EQUATION_1: 22.28 - (0.069 * age) +
      (0.407 * weight) - (0.807 * BMI) - (0.222 * MAC) (adjusted R(2): 0.76; SEE: 1.80
      kg); ASMPRED-EQUATION_2: 16.77 - (0.036 * age) + (0.385 * weight) - (0.873 * BMI)
      (adjusted R(2): 0.73; SEE: 1.90 kg). The mean bias from the CV group between
      ASMDEXA and the predictive equations is as follows: ASMDEXA - ASMPRED-EQUATION_1:
      0.29 +/- 2.6 kg (LOA: -4.80, 5.40 kg); ASMDEXA - ASMPRED-EQUATION_2: 0.13 +/- 2.5
      kg (LOA: -4.77, 5.0 kg). No significant difference was observed between measured
      ASMDEXA and estimated ASM (ASMDEXA: 16.4 +/- 3.9 kg; ASMPRED-EQUATION_1: 16.7 +/-
      3.2 kg (P = 0.379); ASMPRED-EQUATION_2: 16.6 +/- 3.2 kg (P = 0.670)).
      CONCLUSIONS: we have developed and cross-validated novel anthropometric
      prediction equations against DEXA for the estimate of ASM designed for
      application in older orthopaedic patients. Our equation may be of use as an
      alternative to DEXA in the diagnosis of skeletal muscle wasting syndromes.
      Further validation studies are required to determine the clinical utility of our
      equation across other settings, including hip fracture patients admitted from
      residential care, and also with a longer-term follow-up.

PMID- 25049263
TI  - Hypocaloric, high-protein nutrition therapy for critically ill patients with
      obesity.
AB  - We published the first article that addressed hypocaloric, high-protein enteral
      nutrition therapy for critically ill patients with obesity more than 10 years
      ago. This study demonstrated that it was possible to successfully achieve this
      mode of therapy with a commercially available high-protein enteral formula and
      concurrent use of protein supplements. This study was also the first to
      demonstrate improved clinical outcomes with the use of hypocaloric, high-protein
      nutrition therapy. The results of this study, its unique findings, and
      shortcomings are discussed. Subsequent studies have added clarity to the
      effective use of this therapy, including its use in home parenteral nutrition
      patients, patients with class III obesity, and older patients with obesity. 

PMID- 25049264
TI  - Quantum and Multidimensional Explanations in a Neurobiological Context of Mind.
AB  - This article examines the possible relevance of physical-mathematical
      multidimensional or quantum concepts aiming at understanding the (human) mind in
      a neurobiological context. Some typical features of the quantum and
      multidimensional concepts are briefly introduced, including entanglement,
      superposition, holonomic, and quantum field theories. Next, we consider
      neurobiological principles, such as the brain and its emerging (physical) mind,
      evolutionary and ontological origins, entropy, syntropy/neg-entropy, causation,
      and brain energy metabolism. In many biological processes, including biochemical
      conversions, protein folding, and sensory perception, the ubiquitous involvement
      of quantum mechanisms is well recognized. Quantum and multidimensional approaches
      might be expected to help describe and model both brain and mental processes, but
      an understanding of their direct involvement in mental activity, that is, without
      mediation by molecular processes, remains elusive. More work has to be done to
      bridge the gap between current neurobiological and physical-mathematical concepts
      with their associated quantum-mind theories. 

PMID- 25049265
TI  - Transoral robotic versus open surgical approaches to oropharyngeal squamous cell
      carcinoma by human papillomavirus status.
AB  - OBJECTIVES: (1) Investigate oncologic survival outcomes and (2) analyze the
      impact of human papillomavirus status on prognosis in patients with oropharyngeal
      squamous cell carcinoma treated with transoral robotic versus open surgery. STUDY
      DESIGN: Retrospective cohort study. SETTING: Tertiary care referral center,
      University of Alabama at Birmingham Hospital. SUBJECTS: One hundred thirty total
      (65 per treatment arm) with primary oropharyngeal squamous cell carcinoma
      (OPSCC). METHODS: Patients treated for primary oropharyngeal squamous cell
      carcinoma with either transoral robotic (TORS) or open surgery plus standard of
      care adjuvant therapy between October 2004 and March 2012 were matched based on
      TNM staging before a retrospective chart review was performed. Carcinoma tissue
      was stained both prospectively and retrospectively with CINtec p16-INK4a kits for
      surrogate human papillomavirus typing. Recurrence-free survival was used to
      evaluate the impact of human papillomavirus tumor status and method of surgical
      intervention on prognosis. RESULTS: As a whole, patients treated with transoral
      robotic surgery survived more frequently (94%, 91%, 89% at 1, 2, 3 years,
      respectively) than those treated with open surgery (85%, 75%, 73% at 1, 2, 3
      years, correspondingly) (P = .035). The subgroup of patients with human
      papillomavirus-negative malignancies treated with open surgery survived without
      recurrence less frequently at 1, 2, and 3 year rates of 58%, 25%, 25%,
      respectively (P < .01). CONCLUSION: These retrospective data suggest that
      oncologic outcomes are not being sacrificed when patients with OPSCC are treated
      with TORS instead of open surgery regardless of tumor human papillomavirus
      immunohistochemical staining.

PMID- 25049266
TI  - Phylogeny and generic limits in the sister tribes Psychotrieae and Palicoureeae
      (Rubiaceae): Evolution of schizocarps in Psychotria and origins of bacterial leaf
      nodules of the Malagasy species.
AB  - * Premise of the study: The pantropical, species-rich Psychotrieae and
      Palicoureeae are sister tribes of mostly drupe-bearing and nonbacterial leaf
      nodulating species with problematic generic limits. This problem is more
      complicated in Psychotrieae due to the paraphyly of the genus Psychotria, the
      lack of diagnostic characters for some major lineages, and the poor sampling from
      some biodiversity hotspots. Schizocarps and bacterial leaf nodules have been used
      for recognizing formal groups in Psychotrieae, but their evolution and taxonomic
      value have not been studied using a robust phylogeny of the tribe.* Methods: We
      analyzed 287 samples from the entire ranges of the tribes, with particular
      emphasis on the Western Indian Ocean region, with the Bayesian Markov chain Monte
      Carlo method.* Key results: All allied Psychotria genera investigated are nested
      within a paraphyletic Psychotria. Schizocarps evolved independently two times
      within Psychotria, and one reversal back to the drupaceous condition is inferred.
      The Malagasy leaf-nodulated Psychotrieae (except Apomuria bullata) and the
      Comorian non-leaf-nodulated Psychotria conocarpa are nested within the (African)
      leaf-nodulated clade. Within Palicoureeae, Chassalia is paraphyletic with respect
      to Geophila sensu stricto, and the Malagasy Geophila gerrardii and the African
      Hymenocoleus are closely related.* Conclusions: A widely circumscribed Psychotria
      encompassing the entire Psychotrieae is supported. Within Psychotria, two
      separate origins of schizocarps from drupes, one reversal back to the drupaceous
      condition, and two independent origins of the Malagasy leaf-nodulated species are
      inferred. A new genus Puffia is described to accommodate Geophila gerrardii, and
      a narrow circumscription of Chassalia is adopted. Thirty-two new combinations,
      two lectotypifications, and 25 new names are presented.

PMID- 25049267
TI  - The polyploidy revolution then...and now: Stebbins revisited.
AB  - Polyploidy has long been considered a major force in plant evolution. G. Ledyard
      Stebbins, Jr., an architect of the Modern Synthesis, elegantly addressed a broad
      range of topics, from genes to chromosomes to deep phylogeny, but some of his
      most lasting insights came in the study of polyploidy. Here, we review the
      immense impact of his work on polyploidy over more than 60 years, from his
      entrance into this fledgling field in the 1920s until the end of his career.
      Stebbins and his contemporaries developed a model of polyploid evolution that
      persisted for nearly half a century. As new perspectives emerged in the 1980s and
      new genetic tools for addressing key aspects of polyploidy have become available,
      a new paradigm of polyploidy has replaced much of the Stebbinsian framework. We
      review that paradigm shift and emphasize those areas in which the ideas of
      Stebbins continue to propel the field forward, as well as those areas in which
      the field was held back; we also note new directions that plant geneticists and
      evolutionists are now exploring in polyploidy research. Perhaps the most
      important conclusion from recent and ongoing studies of polyploidy is that,
      following Levin and others, polyploidy may propel a population into a new
      adaptive sphere given the myriad changes that accompany genome doubling.

PMID- 25049268
TI  - Gohta Goshima: questing for answers on the mitotic spindle.

PMID- 25049270
TI  - The general amino acid control pathway regulates mTOR and autophagy during
      serum/glutamine starvation.
AB  - Organisms have evolved elaborate mechanisms to adjust intracellular nutrient
      levels in response to fluctuating availability of exogenous nutrients. During
      starvation, cells can enhance amino acid uptake and synthesis through the general
      amino acid control (GAAC) pathway, whereas nonessential cellular contents are
      recycled by autophagy. How these two pathways are coordinated in response to
      starvation is currently unknown. Here we show that the GAAC pathway couples
      exogenous amino acid availability with autophagy. Starvation caused deactivation
      of mTOR, which then activated autophagy. In parallel, serum/glutamine starvation
      activated the GAAC pathway, which up-regulated amino acid transporters, leading
      to increased amino acid uptake. This elevated the intracellular amino acid level,
      which in turn reactivated mTOR and suppressed autophagy. Knockdown of activating
      transcription factor 4, the major transcription factor in the GAAC pathway, or of
      SLC7A5, a leucine transporter, caused impaired mTOR reactivation and much higher
      levels of autophagy. Thus, the GAAC pathway modulates autophagy by regulating
      amino acid uptake and mTOR reactivation during serum/glutamine starvation. 

PMID- 25049269
TI  - Targeting potassium channels in cancer.
AB  - Potassium channels are pore-forming transmembrane proteins that regulate a
      multitude of biological processes by controlling potassium flow across cell
      membranes. Aberrant potassium channel functions contribute to diseases such as
      epilepsy, cardiac arrhythmia, and neuromuscular symptoms collectively known as
      channelopathies. Increasing evidence suggests that cancer constitutes another
      category of channelopathies associated with dysregulated channel expression.
      Indeed, potassium channel-modulating agents have demonstrated antitumor efficacy.
      Potassium channels regulate cancer cell behaviors such as proliferation and
      migration through both canonical ion permeation-dependent and noncanonical ion
      permeation-independent functions. Given their cell surface localization and well
      known pharmacology, pharmacological strategies to target potassium channel could
      prove to be promising cancer therapeutics. 

PMID- 25049271
TI  - Klar ensures thermal robustness of oskar localization by restraining RNP
      motility.
AB  - Communication usually applies feedback loop-based filters and amplifiers to
      ensure undistorted delivery of messages. Such an amplifier acts during Drosophila
      melanogaster midoogenesis, when oskar messenger ribonucleic acid (mRNA) anchoring
      depends on its own locally translated protein product. We find that the motor
      regulator Klar beta mediates a gain-control process that prevents saturation
      based distortions in this positive feedback loop. We demonstrate that, like oskar
      mRNA, Klar beta localizes to the posterior pole of oocytes in a kinesin-1
      dependent manner. By live imaging and semiquantitative fluorescent in situ
      hybridization, we show that Klar beta restrains oskar ribonucleoprotein motility
      and decreases the posterior-ward translocation of oskar mRNA, thereby adapting
      the rate of oskar delivery to the output of the anchoring machinery. This
      negative regulatory effect of Klar is particularly important for overriding
      temperature-induced changes in motility. We conclude that by preventing defects
      in oskar anchoring, this mechanism contributes to the developmental robustness of
      a poikilothermic organism living in a variable temperature environment. 

PMID- 25049272
TI  - AGO3 Slicer activity regulates mitochondria-nuage localization of Armitage and
      piRNA amplification.
AB  - In Drosophila melanogaster the reciprocal "Ping-Pong" cycle of PIWI-interacting
      RNA (piRNA)-directed RNA cleavage catalyzed by the endonuclease (or "Slicer")
      activities of the PIWI proteins Aubergine (Aub) and Argonaute3 (AGO3) has been
      proposed to expand the secondary piRNA population. However, the role of AGO3/Aub
      Slicer activity in piRNA amplification remains to be explored. We show that AGO3
      Slicer activity is essential for piRNA amplification and that AGO3 inhibits the
      homotypic Aub:Aub Ping-Pong process in a Slicer-independent manner. We also find
      that expression of an AGO3 Slicer mutant causes ectopic accumulation of Armitage,
      a key component in the primary piRNA pathway, in the Drosophila melanogaster
      germline granules known as nuage. AGO3 also coexists and interacts with Armitage
      in the mitochondrial fraction. Furthermore, AGO3 acts in conjunction with the
      mitochondria-associated protein Zucchini to control the dynamic subcellular
      localization of Armitage between mitochondria and nuage in a Slicer-dependent
      fashion. Collectively, our findings uncover a new mechanism that couples
      mitochondria with nuage to regulate secondary piRNA amplification. 

PMID- 25049273
TI  - Excess centrosomes disrupt endothelial cell migration via centrosome scattering.
AB  - Supernumerary centrosomes contribute to spindle defects and aneuploidy at
      mitosis, but the effects of excess centrosomes during interphase are poorly
      understood. In this paper, we show that interphase endothelial cells with even
      one extra centrosome exhibit a cascade of defects, resulting in disrupted cell
      migration and abnormal blood vessel sprouting. Endothelial cells with
      supernumerary centrosomes had increased centrosome scattering and reduced
      microtubule (MT) nucleation capacity that correlated with decreased Golgi
      integrity and randomized vesicle trafficking, and ablation of excess centrosomes
      partially rescued these parameters. Mechanistically, tumor endothelial cells with
      supernumerary centrosomes had less centrosome-localized gamma-tubulin, and Plk1
      blockade prevented MT growth, whereas overexpression rescued centrosome gamma
      tubulin levels and centrosome dynamics. These data support a model whereby
      centrosome-MT interactions during interphase are important for centrosome
      clustering and cell polarity and further suggest that disruption of interphase
      cell behavior by supernumerary centrosomes contributes to pathology independent
      of mitotic effects. 

PMID- 25049274
TI  - Ankyrin-G palmitoylation and betaII-spectrin binding to phosphoinositide lipids
      drive lateral membrane assembly.
AB  - Ankyrin-G and betaII-spectrin colocalize at sites of cell-cell contact in
      columnar epithelial cells and promote lateral membrane assembly. This study
      identifies two critical inputs from lipids that together provide a rationale for
      how ankyrin-G and betaII-spectrin selectively localize to Madin-Darby canine
      kidney (MDCK) cell lateral membranes. We identify aspartate-histidine-histidine
      cysteine 5/8 (DHHC5/8) as ankyrin-G palmitoyltransferases required for ankyrin-G
      lateral membrane localization and for assembly of lateral membranes. We also find
      that betaII-spectrin functions as a coincidence detector that requires
      recognition of both ankyrin-G and phosphoinositide lipids for its lateral
      membrane localization. DHHC5/8 and betaII-spectrin colocalize with ankyrin-G in
      micrometer-scale subdomains within the lateral membrane that are likely sites for
      palmitoylation of ankyrin-G. Loss of either DHHC5/8 or ankyrin-G-betaII-spectrin
      interaction or betaII-spectrin-phosphoinositide recognition through its
      pleckstrin homology domain all result in failure to build the lateral membrane.
      In summary, we identify a functional network connecting palmitoyltransferases
      DHHC5/8 with ankyrin-G, ankyrin-G with betaII-spectrin, and betaII-spectrin with
      phosphoinositides that is required for the columnar morphology of MDCK epithelial
      cells. 

PMID- 25049276
TI  - Caution over use of ES2 as a model of ovarian clear cell carcinoma.

PMID- 25049275
TI  - A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and
      promotes tumor dissemination.
AB  - The mechanisms by which tumor cells metastasize and the role of endocytic
      proteins in this process are not well understood. We report that overexpression
      of the GTPase RAB5A, a master regulator of endocytosis, is predictive of
      aggressive behavior and metastatic ability in human breast cancers. RAB5A is
      necessary and sufficient to promote local invasion and distant dissemination of
      various mammary and nonmammary tumor cell lines, and this prometastatic behavior
      is associated with increased intratumoral cell motility. Specifically, RAB5A is
      necessary for the formation of invadosomes, membrane protrusions specialized in
      extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5
      dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix
      metalloprotease [MT1-MMP] and beta3 integrin) required for invadosome formation
      in response to motogenic stimuli. This trafficking circuitry is necessary for
      spatially localized hepatocyte growth factor (HGF)/MET signaling that drives
      invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal
      carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs
      promote tumor dissemination by controlling a proteolytic, mesenchymal invasive
      program. 

PMID- 25049278
TI  - A hereditary bleeding disorder resulting from a premature stop codon in
      thrombomodulin (p.Cys537Stop).
AB  - In this study, we describe a novel thrombomodulin (TM) mutation (c.1611C>A) that
      codes for a change from cysteine 537 to a premature stop codon (p.Cys537Stop).
      Three members of a family with a history of posttraumatic bleeding were
      identified to be heterozygous for this TM mutation. All coagulation screening
      tests, coagulation factor assays, and platelet function test results were within
      normal limits. However, the endogenous thrombin potential was markedly reduced at
      low-tissue factor concentration, and failure to correct with normal plasma
      indicated the presence of a coagulation inhibitor. Plasma TM levels were highly
      elevated (433-845 ng/ml, normal range 2-8 ng/ml, equating to 5 to 10 nM), and the
      addition of exogenous protein C further decreased thrombin generation. The
      mutation, p.Cys537Stop, results in a truncation within the carboxyl-terminal
      transmembrane helix. We predict that as a consequence of the truncation, the
      variant TM is shed from the endothelial surface into the blood plasma. This would
      promote systemic protein C activation and early cessation of thrombin generation
      within a developing hemostatic clot, thereby explaining the phenotype of
      posttraumatic bleeding observed within this family. 

PMID- 25049279
TI  - Factors that predict thrombosis in relatives of patients with venous
      thromboembolism.
AB  - When counseling first-degree relatives of patients with venous thromboembolism
      (VTE), it is important to know whether factors other than thrombophilia influence
      their risk for thrombosis. We assessed the risk for VTE in 915 first-degree
      relatives of patients with provoked VTE, compared this with the risk in 1752
      first-degree relatives of patients with unprovoked VTE, and then combined data
      from the 2 groups of relatives to identify predictors of thrombosis. There had
      been 123 VTEs in 2617 first-degree relatives (0.12 per 100 person-years). The
      risk for VTE in first-degree relatives was higher if the index cases had an
      unprovoked compared with a provoked VTE (odds ratio [OR], 2.38; 95% confidence
      interval [CI], 1.43-3.85), if the index case was younger (OR, 0.97 per year
      older; 95% CI, 0.96-0.99), and if an additional family member had VTE (OR, 2.71;
      95% CI, 2.22-3.31). Among first-degree relatives of an index case with factor V
      Leiden or the prothrombin 20210A gene variant, the presence of these
      abnormalities also predicted thrombosis (OR, 4.42; 95% CI, 1.35-14.38). We
      conclude that thrombosis at a young age and unprovoked VTE predict VTE in first
      degree relatives, and that the influence of these 2 factors is additive. 

PMID- 25049280
TI  - Defining minimal residual disease in acute myeloid leukemia: which platforms are
      ready for "prime time"?
AB  - The past 40 years have witnessed major advances in defining the cytogenetic
      aberrations, mutational landscape, epigenetic profiles, and expression changes
      underlying hematological malignancies. Although it has become apparent that acute
      myeloid leukemia (AML) is highly heterogeneous at the molecular level, the
      standard framework for risk stratification guiding transplant practice in this
      disease remains largely based on pretreatment assessment of cytogenetics and a
      limited panel of molecular genetic markers, coupled with morphological assessment
      of bone marrow (BM) blast percentage after induction. However, application of
      more objective methodology such as multiparameter flow cytometry (MFC) has
      highlighted the limitations of morphology for reliable determination of remission
      status. Moreover, there is a growing body of evidence that detection of
      subclinical levels of leukemia (ie, minimal residual disease, MRD) using MFC or
      molecular-based approaches provides powerful independent prognostic information.
      Consequently, there is increasing interest in the use of MRD detection to provide
      early end points in clinical trials and to inform patient management. However,
      implementation of MRD assessment into clinical practice remains a major
      challenge, hampered by differences in the assays and preferred analytical methods
      employed between routine laboratories. Although this should be addressed through
      adoption of standardized assays with external quality control, it is clear that
      the molecular heterogeneity of AML coupled with increasing understanding of its
      clonal architecture dictates that a "one size fits all" approach to MRD detection
      in this disease is not feasible. However, with the range of platforms now
      available, there is considerable scope to realistically track treatment response
      in every patient. 

PMID- 25049281
TI  - Endothelial cell protein C receptor: a multiliganded and multifunctional
      receptor.
AB  - Endothelial cell protein C receptor (EPCR) was first identified and isolated as a
      cellular receptor for protein C on endothelial cells. EPCR plays a crucial role
      in the protein C anticoagulant pathway by promoting protein C activation. In the
      last decade, EPCR has received wide attention after it was discovered to play a
      key role in mediating activated protein C (APC)-induced cytoprotective effects,
      including antiapoptotic, anti-inflammatory, and barrier stabilization. APC
      elicits cytoprotective signaling through activation of protease activated
      receptor-1 (PAR1). Understanding how EPCR-APC induces cytoprotective effects
      through activation of PAR1, whose activation by thrombin is known to induce a
      proinflammatory response, has become a major research focus in the field. Recent
      studies also discovered additional ligands for EPCR, which include factor VIIa,
      Plasmodium falciparum erythrocyte membrane protein, and a specific variant of the
      T-cell receptor. These observations open unsuspected new roles for EPCR in
      hemostasis, malaria pathogenesis, innate immunity, and cancer. Future research on
      these new discoveries will undoubtedly expand our understanding of the role of
      EPCR in normal physiology and disease, as well as provide novel insights into
      mechanisms for EPCR multifunctionality. Comprehensive understanding of EPCR may
      lead to development of novel therapeutic modalities in treating hemophilia,
      inflammation, cerebral malaria, and cancer. 

PMID- 25049282
TI  - A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma
      cell survival and drug resistance.
AB  - Hedgehog (Hh) signaling plays an important role in the oncogenesis of B-cell
      malignancies such as multiple myeloma (MM). However, the source of Hh ligand
      sonic hedgehog (SHH) and its target cells remains controversial. Previous studies
      showed that stromally induced Hh signaling is essential for the tumor cells and
      that CD19(+)CD138(-) MM stem cells are the target cells of Hh signaling. Here we
      demonstrate that SHH was mainly secreted by human myeloma cells but not by
      stromal cells in MM bone marrow. Autocrine SHH enhanced CD138(+) myeloma cell
      proliferation and protected myeloma cells from spontaneous and stress-induced
      apoptosis. More importantly, autocrine SHH protected myeloma cells against
      chemotherapy-induced apoptosis in vitro and in vivo. Combinational treatment with
      chemotherapy and SHH-neutralizing antibody displayed synergistic antimyeloma
      effects. Mechanistic studies showed that SHH signaling activated the SHH/GLI1/BCL
      2 axis, leading to the inhibition of myeloma cell apoptosis. Thus, this study
      identifies the myeloma autocrine Hh signaling pathway as a potential target for
      the treatment of MM. Targeting this pathway may improve the efficacy of
      chemotherapy in MM patients. 

PMID- 25049283
TI  - Invariant NKT cells with chimeric antigen receptor provide a novel platform for
      safe and effective cancer immunotherapy.
AB  - Advances in the design of chimeric antigen receptors (CARs) have improved the
      antitumor efficacy of redirected T cells. However, functional heterogeneity of
      CAR T cells limits their therapeutic potential and is associated with toxicity.
      We proposed that CAR expression in Valpha24-invariant natural killer T (NKT)
      cells can build on the natural antitumor properties of these cells while their
      restriction by monomorphic CD1d limits toxicity. Primary human NKT cells were
      engineered to express a CAR against the GD2 ganglioside (CAR.GD2), which is
      highly expressed by neuroblastoma (NB). We compared CAR.GD2 constructs that
      encoded the CD3zeta chain alone, with CD28, 4-1BB, or CD28 and 4-1BB
      costimulatory endodomains. CAR.GD2 expression rendered NKT cells highly cytotoxic
      against NB cells without affecting their CD1d-dependent reactivity. We observed a
      striking T helper 1-like polarization of NKT cells by 4-1BB-containing CARs.
      Importantly, expression of both CD28 and 4-1BB endodomains in the CAR.GD2
      enhanced in vivo persistence of NKT cells. These CAR.GD2 NKT cells effectively
      localized to the tumor site had potent antitumor activity, and repeat injections
      significantly improved the long-term survival of mice with metastatic NB. Unlike
      T cells, CAR.GD2 NKT cells did not induce graft-versus-host disease. These
      results establish the potential of NKT cells to serve as a safe and effective
      platform for CAR-directed cancer immunotherapy.

PMID- 25049286
TI  - Protective effects of colchicine in an experimental rat endometriosis model:
      histopathological evaluation and assessment of TNF-alpha levels.
AB  - OBJECTIVE: Endometriosis is an estrogen-dependent chronic inflammatory disease
      observed in reproductive period. The aim of the present study is to assess the
      efficacy of colchicine, widely used to treat many inflammatory diseases, in an
      experimental rat endometriosis model. STUDY DESIGN: Experimental endometriosis
      was constituted with implantation of autogenous endometrial tissue. Rats were
      divided randomly into 2 groups as colchicine group (n = 8) and control group (n
      =8). Although oral 0.1 mg/kg colchicine was administered 4 weeks to the
      colchicine group, the same amount of saline solution was administered to the
      control group. Before and after 30 days of treatment period, peritoneal and
      tissue tumor necrosis factor alpha (TNF-alpha), the volumes and histopathological
      properties of the implants were evaluated. RESULTS: Although the implant volume
      decreased significantly in the colchicine group (89.2 +/- 13.4 mm(3) to 35.2 +/-
      4.5 mm(3), P < .05), the implant volume increased in the control group (85.1 +/-
      14.2 mm3 to 110.3 +/- 10.5 mm(3), P < .05). When compared to the control group,
      the colchicine group had significantly lower histopathologic sores (1.4 +/- 0.2
      vs 2.6 +/- 0.4, P < .001). Although peritoneal fluid TNF-alpha levels were
      significantly decreased in the colchicine group (45.2 +/- 5.3 pg/mL vs 12.1 +/-
      5.2 pg/mL, P < .001), the peritoneal fluid TNF-alpha levels were significantly
      increased in the control group after the treatment (44.2 +/- 3.5 pg/mL vs 61.3 +/
      12.2 pg/mL; P < .001). Tissue TNF-alpha levels were significantly lower in the
      colchicine group when compared to the control group (45.4 +/- 8.6 pg/mL vs 71.3
      +/- 11.2 pg/mL; P < .001). CONCLUSION: Colchicine resulted in regression of
      endometrial implant volumes in experimental rat endometriosis model and decreased
      peritoneal and tissue TNF-alpha levels.

PMID- 25049285
TI  - Risk factors associated with adverse outcome following extracorporeal life
      support: analysis from 360 consecutive patients.
AB  - OBJECTIVE: Risk factors for adverse outcome after extracorporeal life support
      (ECLS) are yet to be defined. For this purpose, we reviewed our institutional
      data from more than a decade, focusing on patients with ECLS. METHODS: Between
      December 2001 and June 2013, 360 consecutive cardiac surgical patients received
      ECLS for post-cardiotomy cardiogenic shock, with high mortality risk despite
      optimal conventional therapy. Patient demographics, clinical characteristics,
      ECLS-related morbidity, as well as in-hospital and long-term mortality were
      analysed. Multivariate logistic regression analysis was performed to identify
      independent predictors of adverse outcome (failed ECLS weaning, in-hospital
      mortality). RESULTS: The mean age was 62+/-17 years, 76% were male and the mean
      preoperative ejection fraction was 35+/-16%. ECLS was established through
      peripheral (90%) or central thoracic cannulation. The mean duration of ECLS was
      7+/-1 days. Intra-aortic balloon pumps were implanted in 22% of the patients.
      ECLS weaning was successful in 58% and 30% could be discharged from hospital. The
      main cause of death was sepsis (69%). Overall, major cerebrovascular events
      occurred in 12% (bleeding 3%, embolic 9%), limb ischaemia in 13%,
      gastrointestinal complications in 16% and renal replacement therapy in 61%.
      Independent risk factors for adverse outcome were prior cardiorespiratory
      resuscitation (OR: 4.1, 95%CI: 0.34-4.21, p=0.04), pH <7.1 (OR: 2.8, 95%CI: 0.45
      3.28, p=0.01), serum lactate >120 mg/dL (OR: 2.6, 95%CI: 0.75-2.96, p< 0.01),
      norepinephrine dosage >0.5 ug/kg/min (OR: 2.4, 95%CI: 0.35-2.92, p=0.02) and age
      >75 years (OR: 2.0, 95%CI: 0.41-2.88, p=0.02). Kaplan Meier estimates for long
      term survival were 26+/-3% at one year and 22+/-2% at five years. CONCLUSION:
      ECLS therapy offers one-year survival to one quarter of patients with an
      otherwise fatal prognosis. Procedural mortality is low and morbidity at the
      implantation site typically moderate. Thus, prolonged metabolic deterioration in
      combination with high-dose vasopressor support prior to ECLS therapy should be
      avoided, particularly in younger patients.

PMID- 25049287
TI  - A better confidence interval for the sensitivity at a fixed level of specificity
      for diagnostic tests with continuous endpoints.
AB  - For a diagnostic test with continuous measurement, it is often important to
      construct confidence intervals for the sensitivity at a fixed level of
      specificity. Bootstrap-based confidence intervals were shown to have good
      performance as compared to others, and the one by Zhou and Qin (2005) was
      recommended as the best existing confidence interval, named the BTII interval. We
      propose two new confidence intervals based on the profile variance method and
      conduct extensive simulation studies to compare the proposed intervals and the
      BTII intervals under a wide range of conditions. An example from a medical study
      on severe head trauma is used to illustrate application of the new intervals. The
      new proposed intervals generally have better performance than the BTII interval.

PMID- 25049288
TI  - Sapere non aude! - Revisiting The Ailment in the age of the risk society.

PMID- 25049290
TI  - Involuntary and restrictive treatments.

PMID- 25049289
TI  - Our College 50 years on: broadening our horizon.

PMID- 25049292
TI  - From the President.

PMID- 25049294
TI  - New premises to provide an enhanced presence in New Zealand.

PMID- 25049295
TI  - College Fellows recognised in Queen's Birthday 2014 Honours List.

PMID- 25049296
TI  - Asia Pacific Mental Health Workshop 2014.

PMID- 25049297
TI  - Profile: The Membership Engagement Committee.

PMID- 25049299
TI  - Congress Award Winners.

PMID- 25049298
TI  - Congress 2014 wrap.

PMID- 25049300
TI  - Community Survey 2014.

PMID- 25049302
TI  - The role of the physical environment in promoting physical activity in children
      across different group compositions.
AB  - Physical activity is an important health-related behavior, but the environmental
      variables that promote or abate it are not well understood. The purpose of this
      study was to conduct a functional analysis evaluating the effect of the physical
      environment on moderate-to-vigorous physical activity (MVPA) in preschool
      children, and to evaluate the utility of the methodology across different group
      compositions. The Observational System for Recording Physical Activity in
      Children was used to define the test conditions and the measures of physical
      activity for eight preschool children. The functional analysis was implemented
      according to a multi-element experimental design. The highest levels of MVPA were
      observed when fixed playground equipment was available and at least one peer was
      present. Moreover, differential responding was observed across group
      compositions. The implications of this methodology and these findings on the
      development of interventions to increase MVPA are discussed. 

PMID- 25049303
TI  - The global burden of neurologic diseases.

PMID- 25049304
TI  - Central neurogenic hyperventilation.

PMID- 25049305
TI  - International Issues: microfinance in neurologic disorders: a promising role.

PMID- 25049306
TI  - International electives in neurology training: A survey of US and Canadian
      program directors.

PMID- 25049307
TI  - Effects of Bacille Calmette-Guerin after the first demyelinating event in the
      CNS.

PMID- 25049308
TI  - Opinion & special articles: neurology training: to pursue or not to pursue a
      fellowship.

PMID- 25049309
TI  - Teaching Video NeuroImages: semiology and localization of ballistic movements.

PMID- 25049310
TI  - Teaching NeuroImages: unmasking raccoon eyes: a classic clinical sign.

PMID- 25049311
TI  - West Virginia University pediatric stroke registry: clinical description and risk
      factors identification in patients from a rural area.
AB  - PURPOSE: To develop an institutional pediatric stroke database at West Virginia
      University to support the classification and description of clinical and
      radiographic characteristics of pediatric stroke in children living in rural
      areas. METHODS: A custom-made database was developed using Microsoft Access to
      include specific query forms for data retrieval. Data were collected
      retrospectively from electronic medical record of pediatric patients with
      ischemic and hemorrhagic stroke, with emphasis on clinical presentation, risk
      factors, and neuroimaging studies between 2000 and 2012. RESULTS: In the children
      group, vasculitis and hypercoagulable disorders were identified less frequently
      than reported. In the neonate group, only extremely sick, symptomatic patents
      were acutely diagnosed with stroke. CONCLUSION: Patients with the most common
      risk factors for stroke (cardiac disease) were overrepresented. This suggests
      that in children receiving medical attention in rural areas less common risk
      factors for stroke might not be identified, increasing the risk recurrence.
      Increased index of suspicion is needed about pediatric stroke in rural areas, and
      early transfer to a tertiary care center for identification of risk factors is
      mandatory.

PMID- 25049313
TI  - Heart failure in Africa: continuity or change?

PMID- 25049314
TI  - Incidence of sudden cardiac death in athletes: a state-of-the-art review.
AB  - Sudden cardiac death (SCD) is the leading medical cause of death in athletes;
      however, the precise incidence is unknown. The objectives of this review were to
      examine studies on the rate of SCD in athletes, assess the methodological
      strengths and weaknesses used to arrive at estimates, compare studies in athletes
      with estimates in similar populations and arrive at an approximation of the
      incidence of SCD based on the best available evidence. A comprehensive literature
      search was performed in PubMed using key terms related to SCD in athletes.
      Articles were reviewed for relevance and included if they contained information
      on the incidence of SCD in athletes or young persons up to the age of 40. The
      reference list from each manuscript was reviewed for additional relevant
      articles. The methods for case identification were examined, as well as the
      inclusion and exclusion criteria and the precision of the population denominator
      studied. Thirteen studies were found investigating the rate of SCD in athletes
      who ranged in age from 9 to 40. An additional 15 incidence studies were located
      examining the rate of SCD in other populations under the age of 40. Rates of SCD
      varied from 1:917,000 to 1:3000. Studies with higher methodological quality
      consistently yielded incidence rates in the range of 1:40,000 to 1:80,000. Some
      athlete subgroups, specifically men, African-American/black athletes and
      basketball players, appear to be at higher risk. The incidence of SCD in athletes
      is likely higher than traditional estimates which may impact the development of
      more effective prevention strategies.

PMID- 25049315
TI  - Prognostic significance and relationship of worst lead residual ST segment
      elevation with myocardial damage assessed by cardiovascular MRI in myocardial
      infarction.
AB  - OBJECTIVE: To investigate the relation of residual worst lead ST segment
      elevation (WL-STE) after ST segment myocardial infarction (STEMI) with infarct
      size and microvascular injury assessed by cardiovascular magnetic resonance (CMR)
      imaging. BACKGROUND: WL-STE in patients with acute reperfused STEMI has been
      shown to identify high risk patients for major adverse cardiovascular events
      (MACE). However, the relation of WL-STE with myocardial damage is unknown.
      METHODS: In this multicentre study we analysed ECG data 90 min after primary
      percutaneous coronary intervention (PCI) in 763 STEMI patients. WL-STE was
      defined as the absolute magnitude of STE in the most affected lead on the post
      PCI ECG. Patients were categorised into three groups (<1 mm, 1-2 mm, and >=2 mm).
      CMR was performed within 1 week after infarction for comprehensive assessment of
      myocardial damage using a standardised protocol. The primary clinical endpoint
      was MACE defined as death, reinfarction, and new congestive heart failure within
      12 months after infarction. RESULTS: WL-STE <1 mm, 1-2 mm, and >=2 mm was present
      in 155 (20%), 328 (43%), and 280 (37%) patients, respectively. Myocardial damage
      determined by CMR demonstrated a graded relationship of infarct size (median
      (IQR) 13.3 (6.2-20.3)%LV vs 13.7 (7.6-21.3)%LV vs 22.5 (15.6-31.2)%LV, p<0.001),
      the myocardial salvage index (60.8 (37.0-84.5) vs 55.0 (36.6-73.9) vs 42.7 (26.2
      58.2), p<0.001), and microvascular obstruction (0.0 (0.0-0.9)%LV vs 0.0 (0
      1.0)%LV vs 1.2 (0.0-3.6)%LV, p<0.001) across the three groups. WL-STE >=2 mm was
      strongly associated with MACE 12 month after infarction (HR 1.93, 95% CI 1.11 to
      3.37; p=0.02). CONCLUSIONS: This largest CMR study to date correlating post-PCI
      WL-STE with markers of myocardial damage demonstrates that WL-STE is
      significantly associated with infarct size, myocardial salvage, microvascular
      obstruction, and MACE in a high risk STEMI population. TRIAL REGISTRATION NUMBER:
      NCT00712101.

PMID- 25049316
TI  - Insights into intradialytic atrial fibrillation onset mechanisms.

PMID- 25049317
TI  - Minimally Invasive Vacuum-Assisted Closure Therapy With Instillation (Mini-VAC
      Instill) for Pleural Empyema.
AB  - Enthusiasm for minimally invasive thoracic surgery is increasing. Thoracoscopy
      plays a significant therapeutic role in the fibrinopurulent stage (stage II) of
      empyema, in which loculated fluid cannot often be adequately drained by chest
      tube alone. For some debilitated and septic patients, further procedures such as
      open-window thoracostomy (OWT) with daily wound care or vacuum-assisted closure
      (VAC) therapy are necessary. In the present article, we propose a new option of
      minimally invasive VAC therapy including a topical solution of the empyema
      without open-window thoracostomy (Mini-VAC-instill). Three patients who underwent
      surgery using this technique are also presented. The discussion is focused on the
      advantages and disadvantages of the approach. 

PMID- 25049318
TI  - Video processing to locate the tooltip position in surgical eye-hand coordination
      tasks.
AB  - INTRODUCTION: Trajectories of surgical instruments in laparoscopic surgery
      contain rich information about surgeons' performance. In a simulation
      environment, instrument trajectories can be taken by motion sensors attached to
      the instruments. This method is not accepted by surgeons working in the operating
      room due to safety concerns. In this study, a novel approach of acquiring
      instrument trajectories from surgical videos is reported. METHODS: A total of 12
      surgical videos were obtained for this study. The videos were captured during
      simulated laparoscopic procedures where subjects were required to pick up and
      transport an object over 3 different targets using a laparoscopic grasper. An
      algorithm was developed to allow the computer to identify the tip of the grasper
      on each frame of video, and then compute the trajectories of grasper movement.
      RESULTS: The newly developed algorithm successfully identified tool trajectories
      from all 12 surgical videos. To validate the accuracy of this algorithm, the
      location of the tooltip in these videos were also manually labeled. The rate of
      accurate matching between these 2 methods was 98.4% of all video frames.
      DISCUSSION: Identifying tool movement from surgical videos creates an effective
      way to track instrument trajectories. This builds up the foundation for assessing
      psychomotor performance of surgeons in the operating room without jeopardizing
      patient safety.

PMID- 25049319
TI  - Managed care and the dissemination of robotic prostatectomy.
AB  - OBJECTIVE: Robotic prostatectomy has rapidly disseminated over the past decade.
      How managed care, thought by many to be a barrier to new technology, influences
      the dissemination of robotics is unknown. We sought to better understand the
      relationship between a market's managed-care penetration and the dissemination of
      robotic prostatectomy. METHODS: We used SEER-Medicare data from 2003 through 2007
      to identify men >=66 years of age treated with radical prostatectomy for prostate
      cancer. We categorized Health Service Areas (HSAs) according to the degree of
      managed-care penetration (ie, low vs high). We assessed adoption of robotic
      prostatectomy and utilization among adopting HSAs using Cox proportional-hazards
      and Poisson regression models, respectively. RESULTS: Compared with markets with
      little managed care, highly penetrated markets had more racial diversity (24% vs
      15% nonwhite, P < .01), higher population densities (1987 vs 422 people/square
      mile, P < .01), and higher median incomes ($49 374 vs $36 236, P < .01). Robotic
      prostatectomy adoption and utilization increased over time in both HSA
      categories. Compared with low managed-care markets, those with high managed care
      adopted robotic prostatectomy more rapidly (eg, probability 0.37 [low] vs 0.52
      [high] in 2007; P < .01). However, the postadoption utilization of robotic
      prostatectomy was constrained in these highly penetrated markets (eg, probability
      0.66 [low] vs 0.52 [high] in 2007; P < .01). CONCLUSIONS: High managed-care
      penetration was associated with more rapid robotic prostatectomy adoption.
      However, once adopted, utilization increased more slowly in these markets.
      Understanding this paradox is important as more technologies are unveiled in an
      increasingly cost-conscious health care environment.

PMID- 25049320
TI  - Rigid, Variable-View Endoscope in Neurosurgery: First Intraoperative Experience.
AB  - INTRODUCTION: The endoscope became a highly valued visualization tool in
      neurosurgery. However, technical limitations caused by the rigidity of current
      standard endoscopes significantly decrease ergonomy in transcranial neurosurgery.
      Further technological developments will aid enlarging the surgical applicability.
      OBJECTIVE: To evaluate the intraoperative features of a rigid variable-view
      endoscope in neurosurgery. METHODS: We assessed a 4 mm rigid rod lens endoscope
      (EndoCAMeleon, Karl Storz, Tuttlingen, Germany) in the intraoperative setting.
      The device offers a variable angle of view from 15 degrees  to 90 degrees  in one
      plane. The endoscope was used in 3 cases (aneurysm clipping, vestibular
      schwannoma surgery, endoscopic third ventriculostomy) for inspection. RESULTS:
      Direct insertion of the device through the craniotomy/burr hole with the lowest
      angled view (15 degrees ) was always possible. Neurovascular structures crossing
      the access route could be visualized and avoided. This allowed a targeted
      positioning of the endoscope's tip in the operating field. Once the target point
      was reached, viewing direction was changed in one plane from 15 degrees  to 90
      degrees  according to anatomic demands. As the endoscope's tip does not move
      while the lens is rotated, surrounding neurovascular structures are not at risk
      to be injured. However, turning of the lens-controlling wheel in proximity to
      delicate structures may be inconvenient. CONCLUSION: The rigid, variable-view
      endoscope has the potential to become an appreciated visualization tool in
      neuroendoscopy. The steerable lens enables a tremendous expansion of the visual
      field, resulting in higher efficiency for surgeons and increased safety for
      patients.

PMID- 25049321
TI  - Should LVEF be replaced by global longitudinal strain?

PMID- 25049322
TI  - Entering the era of targeted therapy for chronic lymphocytic leukemia: impact on
      the practicing clinician.
AB  - PURPOSE: Chemoimmunotherapy has been the standard of care for chronic lymphocytic
      leukemia (CLL). However, the introduction of B-cell receptor (BCR) kinase
      inhibitors such as ibrutinib has the potential to eliminate the role of
      chemotherapy in the treatment of CLL. How to best incorporate old and new
      therapies for CLL in this landscape is increasingly complex. METHODS: This
      article reviews current data available to clinicians and integrates these data to
      provide a strategy that can be used to approach the treatment of CLL in the era
      of BCR signaling inhibitors. RESULTS: Current strategies separate patients based
      on age or functional status as well as genetics [presence or absence of
      del(17)(p13.1)]. In the era of targeted therapy, this will likely continue based
      on current available data. Phase III studies support chemoimmunotherapy as the
      initial standard therapy for patients without del(17)(p13.1). Choice of
      chemotherapy (fludarabine plus cyclophosphamide, bendamustine, or chlorambucil)
      and anti-CD20 antibody (rituximab, ofatumumab, or obinutuzumab) varies based on
      regimen and patient status. For patients with del(17)(p13.1), no standard initial
      therapy exists, although several options supported by phase II clinical trials
      (methylprednisolone plus alemtuzumab or ibrutinib) seem better than
      chemoimmunotherapy. Treatment of relapsed CLL seems to be best supported by
      ibrutinib-based therapy. Completion of trials with ibrutinib and other new agents
      in the near future will offer opportunity for chemotherapy-free treatment across
      all groups of CLL. CONCLUSION: Therapy for CLL has evolved significantly over the
      past decade with introduction of targeted therapy for CLL. This has the potential
      to completely transform how CLL is treated in the future.

PMID- 25049324
TI  - The never-ending story: finding a role for neoadjuvant chemotherapy in the
      management of head and neck cancer.

PMID- 25049323
TI  - African Americans with cancer pain are more likely to receive an analgesic with
      toxic metabolite despite clinical risks: a mediation analysis study.
AB  - PURPOSE: Renal impairment is highly prevalent among patients with cancer, and
      many patients have undiagnosed chronic kidney disease (CKD) from underlying
      disease, treatment, or both. African American individuals have disproportionate
      risk factors (diabetes, hypertension) predisposing them to CKD. We investigated
      whether African American patients are more likely than white patients to receive
      morphine with 3- and 6-glucuronide metabolites, which are known to be neurotoxic
      and accumulate in CKD; whether insurance type mediates the relationship between
      race and the prescriber's opioid selection; and whether the chosen opioid has a
      resultant negative effect according to race. PATIENTS AND METHODS: Patients (N =
      182) were recruited from oncology clinics within the University of Pennsylvania
      Health System. Inclusion was based on self-identified African American or white
      race, age older than 18 years, and the presence of cancer-related pain plus a
      prescription for morphine or oxycodone. Kidney function was estimated using the
      abbreviated Modification of Diet in Renal Disease formula. RESULTS: Patients with
      CKD who received morphine reported a greater severity of analgesic-related
      adverse effects than patients with CKD who received oxycodone (P = .010).
      Controlling for health insurance type, African American patients had 71% lower
      odds of receiving a prescription of oxycodone than white patients (P < .001).
      Limiting analysis to those with CKD, the effect of private insurance became
      insignificant. However, race still remained a significant predictor of the
      prescribed opioid selection. Race was a strong predictor of adverse effect
      severity in the presence of CKD, and the type of opioid selection partially
      mediated this relationship. CONCLUSION: Reducing racial disparities in the type
      of opioid prescription and understanding mechanisms of disproportionate opioid
      related adverse effects in African American patients might decrease the clinical
      disparities in cancer pain outcomes.

PMID- 25049325
TI  - Effect of routine assessment of specific psychosocial problems on personalized
      communication, counselors' awareness, and distress levels in cancer genetic
      counseling practice: a randomized controlled trial.
AB  - PURPOSE: This study evaluated the efficacy of a cancer genetics-specific
      questionnaire in facilitating communication about, awareness of, and management
      of psychosocial problems, as well as in lowering distress levels. METHODS:
      Individuals referred to genetic counseling for cancer at two family cancer
      clinics in The Netherlands were randomly assigned to an intervention or a control
      group. All participants completed the psychosocial questionnaire before
      counseling. In the intervention group, the counselors received the results of
      this questionnaire before the counseling session. All sessions were audiotaped
      for content analysis. Primary outcomes were the frequency with which psychosocial
      problems were discussed, the genetic counselors' awareness of these problems, and
      their management. Secondary outcomes included cancer worries and psychological
      distress, duration and dynamics of the counseling, and satisfaction. RESULTS: The
      frequency with which psychosocial problems were discussed with 246 participating
      counselees was significantly higher in the intervention group (n = 127) than in
      the control group (n =119; P = .004), as was the counselors' awareness of
      psychosocial problems regarding hereditary predisposition (P < .001), living with
      cancer (P = .01), and general emotions (P < .001). Counselors initiated more
      discussion of psychosocial problems in the intervention group (P < .001), without
      affecting the length of the counseling session. No significant differences were
      found on management (P = .19). The intervention group reported significantly
      lower levels of cancer worries (p = .005) and distress (p = .02) after
      counseling. CONCLUSION: The routine assessment of psychosocial problems by
      questionnaire facilitates genetic counselors' recognition and discussion of their
      clients' psychosocial problems and reduces clients' distress levels.

PMID- 25049326
TI  - Oncology fellows' career plans, expectations, and well-being: do fellows know
      what they are getting into?
AB  - PURPOSE: To evaluate the career plans, professional expectations, and well-being
      of oncology fellows compared with actual experiences of practicing oncologists.
      METHODS: US oncology fellows taking the 2013 Medical Oncology In-Training
      Examination (MedOnc ITE) were invited to participate in an optional
      postexamination survey. The survey evaluated fellows' career plans and
      professional expectations and measured burnout, quality of life (QOL), fatigue,
      and satisfaction with work-life balance (WLB) using standardized instruments.
      Fellows' professional expectations and well-being were compared with actual
      experiences of US oncologists assessed simultaneously. RESULTS: Of the 1,637
      oncology fellows in the United States, 1,373 (83.9%) took the 2013 MedOnc ITE.
      Among these, 1,345 (97.9%) completed the postexamination survey. The frequency of
      burnout among fellows decreased from 43.3% in year 1 to 31.7% in year 2 and 28.1%
      in year 3 (P < .001). Overall, the rate of burnout among fellows and practicing
      oncologists was similar (34.1% v. 33.7%; P = .86). With respect to other
      dimensions of well-being, practicing oncologists had lower fatigue (P < .001) and
      better overall QOL scores (P < .001) than fellows but were less satisfied with
      WLB (P = .0031) and specialty choice (P < .001). Fellows' expectations regarding
      future work hours were 5 to 6 hours per week fewer than oncologists' actual
      reported work hours. Levels of burnout (P = .02) and educational debt (P < or
      =.004) were inversely associated with ITE scores. Fellows with greater
      educational debt were more likely to pursue private practice and less likely to
      plan an academic career. CONCLUSION: Oncology fellows entering practice trade one
      set of challenges for another. Unrealized expectations regarding work hours may
      contribute to future professional dissatisfaction, burnout, and challenges with
      WLB.

PMID- 25049327
TI  - Outcomes of children with BCR-ABL1-like acute lymphoblastic leukemia treated with
      risk-directed therapy based on the levels of minimal residual disease.
AB  - PURPOSE: BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a recently
      identified B-cell ALL (B-ALL)subtype with poor outcome that exhibits a gene
      expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion
      protein. We examined the outcome of children with BCR-ABL1-like ALL treated with
      risk-directed therapy based on minimal residual disease (MRD) levels during
      remission induction. PATIENTS AND METHODS: Among 422 patients with B-ALL enrolled
      onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples
      for gene expression profiling. Next-generation sequencing and/or analysis of
      genes known to be altered in B-ALL were performed in patients with BCR-ABL1
      likeALL who had available material. Outcome was compared between patients with
      and those without BCR-ABL1-like ALL. RESULTS: Forty (11.6%) of the 344 patients
      had BCR-ABL1-like ALL. They were significantly more likely to be male, have Down
      syndrome, and have higher MRD levels on day 19 and at the end of induction than
      did other patients with B-ALL. Among 25 patients comprehensively studied for
      genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had
      fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK
      inhibitors, and seven had mutations involving the Ras signaling pathway. There
      were no significant differences in event-free survival (90.0% +/- 4.7% [SE] v.
      88.4% +/- .9% at 5 years; P = .41or in overall survival (92.5% +/- 4.2% v. 95.1%
      +/- 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1-like
      ALL. CONCLUSION: Patients who have BCR-ABL1-like ALL with poor initial treatment
      response can be salvaged with MRD-based risk-directed therapy and may benefit
      from identification of kinase-activating lesions for targeted therapies.

PMID- 25049328
TI  - Reply to S. Yuan et al.

PMID- 25049329
TI  - Phase III randomized trial of induction chemotherapy in patients with N2 or N3
      locally advanced head and neck cancer.
AB  - PURPOSE: Induction chemotherapy (IC) before radiotherapy lowers distant failure
      (DF) rates in locally advanced squamous cell carcinoma of the head and neck
      (SCCHN). The goal of this phase III trial was to determine whether IC before
      chemoradiotherapy (CRT) further improves survival compared with CRT alone in
      patients with N2 or N3 disease. PATIENTS AND METHODS: Treatment-naive patients
      with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm;
      docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day
      every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1,
      cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5)
      followed by the same CRT regimen (IC + CRT arm). The primary end point was
      overall survival (OS). Secondary end points included DF-free survival, failure
      pattern, and recurrence-free survival (RFS). RESULTS: A total of 285 patients
      were randomly assigned. The most common grade 3 to 4 toxicities during IC were
      febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined),
      they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious
      adverse events were more common in the IC arm (47% v 28%; P = .002). With a
      minimum follow-up of 30 months, there were no statistically significant
      differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free
      survival. CONCLUSION: IC did not translate into improved OS compared with CRT
      alone. However, the study was underpowered because it did not meet the planned
      accrual target, and OS was higher than predicted in both arms. IC cannot be
      recommended routinely in patients with N2 or N3 locally advanced SCCHN.

PMID- 25049331
TI  - Latent membrane protein-specific cytotoxic T lymphocytes: new hope for patients
      with natural killer/T-cell lymphoma?

PMID- 25049330
TI  - Phase II randomized trial comparing sequential first-line everolimus and second
      line sunitinib versus first-line sunitinib and second-line everolimus in patients
      with metastatic renal cell carcinoma.
AB  - PURPOSE: A multicenter, randomized phase II trial, RECORD-3, was conducted to
      compare first-line everolimus followed by sunitinib at progression with the
      standard sequence of first-line sunitinib followed by everolimus in patients with
      metastatic renal cell carcinoma. PATIENTS AND METHODS: RECORD-3 used a crossover
      treatment design. The primary objective was to assess progression-free survival
      (PFS) noninferiority of first-line everolimus compared with first-line sunitinib.
      Secondary end points included combined PFS for each sequence, overall survival
      (OS), and safety. RESULTS: Of 471 enrolled patients, 238 were randomly assigned
      to first-line everolimus followed by sunitinib, and 233 were randomly assigned to
      first-line sunitinib followed by everolimus. The primary end point was not met;
      the median PFS was 7.9 months for first-line everolimus and 10.7 months for first
      line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who
      discontinued first-line, 108 (45%) crossed over from everolimus to second-line
      sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus.
      The median combined PFS was 21.1 months for sequential everolimus then sunitinib
      and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI,
      0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then
      sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2;
      95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line
      everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45%
      and 51%, respectively), and diarrhea (38% and 57%, respectively). CONCLUSION:
      Everolimus did not demonstrate noninferiority compared with sunitinib as a first
      line therapy. The trial results support the standard treatment paradigm of first
      line sunitinib followed by everolimus at progression.

PMID- 25049332
TI  - Luminal B breast cancer: molecular characterization, clinical management, and
      future perspectives.
AB  - Gene expression profiling has reshaped our understanding of breast cancer by
      defining and characterizing four main intrinsic molecular subtypes: human
      epidermal growth factor receptor 2-enriched, basal-like, luminal A, and luminal B
      subtypes. Luminal B breast cancer has been reported to have lower expression of
      hormone receptors, higher expression of proliferation markers, and higher
      histologic grade than luminal A. It also exhibits worse prognosis and has a
      distinct profile of response to hormone therapy and chemotherapy. Although
      luminal cancers share similarities, the studies conducted in recent years using
      next-generation sequencing technology show that luminal A and B breast cancers
      should be perceived as distinct entities, with specific oncogenic drivers, rather
      than more proliferative varieties of luminal tumors. This review discusses the
      definition and molecular characterization of luminal B breast cancer and presents
      the available clinical evidence for chemotherapy and endocrine therapy patterns
      of response. It also provides an overview of ongoing research on molecularly
      targeted agents for this disease. 

PMID- 25049333
TI  - MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity
      through distinct T cell receptor usage.
AB  - Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell
      receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic
      major histocompatibility complex (MHC)-like molecule MR1. The highly conserved
      nature of MR1 in conjunction with biased MAIT TCRalpha chain usage is widely
      thought to indicate limited ligand presentation and discrimination within a
      pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT
      cells responsive to three classes of microbes. Substantial diversity and
      heterogeneity were apparent across the functional MAIT cell repertoire as a
      whole, especially for TCRbeta chain sequences. Moreover, different pathogen
      specific responses were characterized by distinct TCR usage, both between and
      within individuals, suggesting that MAIT cell adaptation was a direct consequence
      of exposure to various exogenous MR1-restricted epitopes. In line with this
      interpretation, MAIT cell clones with distinct TCRs responded differentially to a
      riboflavin metabolite. These results suggest that MAIT cells can discriminate
      between pathogen-derived ligands in a clonotype-dependent manner, providing a
      basis for adaptive memory via recruitment of specific repertoires shaped by
      microbial exposure. 

PMID- 25049334
TI  - Trans-nodal migration of resident dendritic cells into medullary interfollicular
      regions initiates immunity to influenza vaccine.
AB  - Dendritic cells (DCs) are well established as potent antigen-presenting cells
      critical to adaptive immunity. In vaccination approaches, appropriately
      stimulating lymph node-resident DCs (LNDCs) is highly relevant to effective
      immunization. Although LNDCs have been implicated in immune response, their
      ability to directly drive effective immunity to lymph-borne antigen remains
      unclear. Using an inactive influenza vaccine model and whole node imaging
      approaches, we observed surprising responsiveness of LNDC populations to vaccine
      arrival resulting in a transnodal repositioning into specific antigen collection
      sites within minutes after immunization. Once there, LNDCs acquired viral antigen
      and initiated activation of viral specific CD4(+) T cells, resulting in germinal
      center formation and B cell memory in the absence of skin migratory DCs.
      Together, these results demonstrate an unexpected stimulatory role for LNDCs
      where they are capable of rapidly locating viral antigen, driving early
      activation of T cell populations, and independently establishing functional
      immune response. 

PMID- 25049335
TI  - Acid sphingomyelinase modulates the autophagic process by controlling lysosomal
      biogenesis in Alzheimer's disease.
AB  - In Alzheimer's disease (AD), abnormal sphingolipid metabolism has been reported,
      although the pathogenic consequences of these changes have not been fully
      characterized. We show that acid sphingomyelinase (ASM) is increased in
      fibroblasts, brain, and/or plasma from patients with AD and in AD mice, leading
      to defective autophagic degradation due to lysosomal depletion. Partial genetic
      inhibition of ASM (ASM(+/-)) in a mouse model of familial AD (FAD; amyloid
      precursor protein [APP]/presenilin 1 [PS1]) ameliorated the autophagocytic defect
      by restoring lysosomal biogenesis, resulting in improved AD clinical and
      pathological findings, including reduction of amyloid-beta (Abeta) deposition and
      improvement of memory impairment. Similar effects were noted after pharmacologic
      restoration of ASM to the normal range in APP/PS1 mice. Autophagic dysfunction in
      neurons derived from FAD patient induced pluripotent stem cells (iPSCs) was
      restored by partial ASM inhibition. Overall, these results reveal a novel
      mechanism of ASM pathogenesis in AD that leads to defective autophagy due to
      impaired lysosomal biogenesis and suggests that partial ASM inhibition is a
      potential new therapeutic intervention for the disease. 

PMID- 25049337
TI  - 18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure
      overload-induced maladaptive cardiac remodeling.
AB  - N-3 polyunsaturated fatty acids (PUFAs) have potential cardiovascular benefit,
      although the mechanisms underlying this effect remain poorly understood. Fat-1
      transgenic mice expressing Caenorhabditis elegans n-3 fatty acid desaturase,
      which is capable of producing n-3 PUFAs from n-6 PUFAs, exhibited resistance to
      pressure overload-induced inflammation and fibrosis, as well as reduced cardiac
      function. Lipidomic analysis revealed selective enrichment of eicosapentaenoic
      acid (EPA) in fat-1 transgenic bone marrow (BM) cells and EPA-metabolite 18
      hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 transgenic macrophages. BM
      transplantation experiments revealed that fat-1 transgenic BM cells, but not fat
      1 transgenic cardiac cells, contributed to the antiremodeling effect and that the
      18-HEPE-rich milieu in the fat-1 transgenic heart was generated by BM-derived
      cells, most likely macrophages. 18-HEPE inhibited macrophage-mediated
      proinflammatory activation of cardiac fibroblasts in culture, and in vivo
      administration of 18-HEPE reproduced the fat-1 mice phenotype, including
      resistance to pressure overload-induced maladaptive cardiac remodeling. 

PMID- 25049336
TI  - A molecular basis underpinning the T cell receptor heterogeneity of mucosal
      associated invariant T cells.
AB  - Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor
      (TCR) alpha-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which
      pairs with an array of TCR beta-chains. MAIT TCRs can bind folate- and riboflavin
      based metabolites restricted by the major histocompatibility complex (MHC)
      related class I-like molecule, MR1. However, the impact of MAIT TCR and MR1
      ligand heterogeneity on MAIT cell biology is unclear. We show how a previously
      uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly stabilized
      MR1, potently up-regulated MR1 cell surface expression, and inhibited MAIT cell
      activation. These enhanced properties of Ac-6-FP were attributable to structural
      alterations in MR1 that subsequently affected MAIT TCR recognition via
      conformational changes within the complementarity-determining region (CDR) 3beta
      loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3beta
      hypervariability impacted on MAIT TCR recognition by altering TCR flexibility and
      contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4, and
      TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based
      antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1
      contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential TRAJ
      gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag docking
      mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition in an Ag
      dependent manner, thereby modulating MAIT cell recognition. 

PMID- 25049338
TI  - Prevention of traumatic stress in mothers of preterms: 6-month outcomes.
AB  - OBJECTIVE: Symptoms of posttraumatic stress disorder are a well-recognized
      phenomenon in mothers of preterm infants, with implications for maternal health
      and infant outcomes. This randomized controlled trial evaluated 6-month outcomes
      from a skills-based intervention developed to reduce symptoms of posttraumatic
      stress disorder, anxiety, and depression. METHODS: One hundred five mothers of
      preterm infants were randomly assigned to (1) a 6- or 9-session intervention
      based on principles of trauma-focused cognitive behavior therapy with infant
      redefinition or (2) a 1-session active comparison intervention based on education
      about the NICU and parenting of the premature infant. Outcome measures included
      the Davidson Trauma Scale, the Beck Depression Inventory II, and the Beck Anxiety
      Inventory. Participants were assessed at baseline, 4 to 5 weeks after birth, and
      6 months after the birth of the infant. RESULTS: At the 6-month assessment, the
      differences between the intervention and comparison condition were all
      significant and sizable and became more pronounced when compared with the 4- to 5
      week outcomes: Davidson Trauma Scale (Cohen's d = -0.74, P < .001), Beck Anxiety
      Inventory (Cohen's d = -0.627, P = .001), Beck Depression Inventory II (Cohen's d
      = -0.638, P = .002). However, there were no differences in the effect sizes
      between the 6- and 9-session interventions. CONCLUSIONS: A brief 6-session
      intervention based on principles of trauma-focused cognitive behavior therapy was
      effective at reducing symptoms of trauma, anxiety, and depression in mothers of
      preterm infants. Mothers showed increased benefits at the 6-month follow-up,
      suggesting that they continue to make use of techniques acquired during the
      intervention phase.

PMID- 25049339
TI  - Successful schools and risky behaviors among low-income adolescents.
AB  - OBJECTIVES: We examined whether exposure to high-performing schools reduces the
      rates of risky health behaviors among low-income minority adolescents and whether
      this is due to better academic performance, peer influence, or other factors.
      METHODS: By using a natural experimental study design, we used the random
      admissions lottery into high-performing public charter high schools in low-income
      Los Angeles neighborhoods to determine whether exposure to successful school
      environments leads to fewer risky (eg, alcohol, tobacco, drug use, unprotected
      sex) and very risky health behaviors (e.g., binge drinking, substance use at
      school, risky sex, gang participation). We surveyed 521 ninth- through twelfth
      grade students who were offered admission through a random lottery (intervention
      group) and 409 students who were not offered admission (control group) about
      their health behaviors and obtained their state-standardized test scores.
      RESULTS: The intervention and control groups had similar demographic
      characteristics and eighth-grade test scores. Being offered admission to a high
      performing school (intervention effect) led to improved math (P < .001) and
      English (P = .04) standard test scores, greater school retention (91% vs. 76%; P
      < .001), and lower rates of engaging in >=1 very risky behaviors (odds ratio =
      0.73, P < .05) but no difference in risky behaviors, such as any recent use of
      alcohol, tobacco, or drugs. School retention and test scores explained 58.0% and
      16.2% of the intervention effect on engagement in very risky behaviors,
      respectively. CONCLUSIONS: Increasing performance of public schools in low-income
      communities may be a powerful mechanism to decrease very risky health behaviors
      among low-income adolescents and to decrease health disparities across the life
      span.

PMID- 25049340
TI  - Treatment outcomes of overweight children and parents in the medical home.
AB  - OBJECTIVE: To test in the primary care setting the short- and long-term efficacy
      of a behavioral intervention that simultaneously targeted an overweight child and
      parent versus an information control (IC) targeting weight control only in the
      child. METHODS: Two- to 5-year-old children who had BMI >=85th percentile and an
      overweight parent (BMI >25 kg/m2) were randomized to Intervention or IC, both
      receiving diet and activity education over 12 months (13 sessions) followed by 12
      month follow-up (3 sessions). Parents in the Intervention group were also
      targeted for weight control and received behavioral intervention. Pediatricians
      in 4 practices enrolled their patients with the assistance of embedded recruiters
      (Practice Enhancement Assistants) who assisted with treatment too. RESULTS: A
      total of 96 of the 105 children randomized (Intervention n = 46; IC n = 50)
      started the program and had data at baseline. Children in the Intervention
      experienced greater reductions in percent over BMI (group * months; P = .002) and
      z-BMI (group * months; P < 0.001) compared with IC throughout treatment and
      follow-up. Greater BMI reduction was observed over time for parents in the
      Intervention compared with IC (P < .001) throughout treatment and follow-up.
      Child weight changes were correlated with parent weight changes at 12 and 24
      months (r = 0.38 and 0.26; P < .001 and P = .03). CONCLUSIONS: Concurrently
      targeting preschool-aged overweight and obese youth and their parents in primary
      care with behavioral intervention results in greater decreases in child percent
      over BMI, z-BMI, and parent BMI compared with IC. The difference between
      Intervention and IC persists after 12 months of follow-up.

PMID- 25049341
TI  - The role of social impact bonds in pediatric health care.

PMID- 25049342
TI  - HIV and child mental health: a case-control study in Rwanda.
AB  - BACKGROUND: The global HIV/AIDS response has advanced in addressing the health
      and well-being of HIV-positive children. Although attention has been paid to
      children orphaned by parental AIDS, children who live with HIV-positive
      caregivers have received less attention. This study compares mental health
      problems and risk and protective factors in HIV-positive, HIV-affected (due to
      caregiver HIV), and HIV-unaffected children in Rwanda. METHODS: A case-control
      design assessed mental health, risk, and protective factors among 683 children
      aged 10 to 17 years at different levels of HIV exposure. A stratified random
      sampling strategy based on electronic medical records identified all known HIV
      positive children in this age range in 2 districts in Rwanda. Lists of all same
      age children in villages with an HIV-positive child were then collected and split
      by HIV status (HIV-positive, HIV-affected, and HIV-unaffected). One child was
      randomly sampled from the latter 2 groups to compare with each HIV-positive child
      per village. RESULTS: HIV-affected and HIV-positive children demonstrated higher
      levels of depression, anxiety, conduct problems, and functional impairment
      compared with HIV-unaffected children. HIV-affected children had significantly
      higher odds of depression (1.68: 95% confidence interval [CI] 1.15-2.44), anxiety
      (1.77: 95% CI 1.14-2.75), and conduct problems (1.59: 95% CI 1.04-2.45) compared
      with HIV-unaffected children, and rates of these mental health conditions were
      similar to HIV-positive children. These results remained significant after
      controlling for contextual variables, there were no significant differences on
      mental health outcomes groups, reflecting a potential explanatory role of factors
      such as daily hardships, caregiver depression, and HIV-related stigma
      [corrected]. CONCLUSIONS: The mental health of HIV-affected children requires
      policy and programmatic responses comparable to HIV-positive children.

PMID- 25049343
TI  - Parental smoking during pregnancy and ADHD in children: the Danish national birth
      cohort.
AB  - BACKGROUND: Prenatal maternal smoking has been associated with attention
      deficit/hyperactivity disorder (ADHD) in children, but the causal nature of this
      association is still under scrutiny. We examined the association with maternal
      smoking and nicotine replacement use during pregnancy, using association with
      paternal smoking as a marker of potential genetic or social confounding. METHODS:
      We included 84 803 singletons who participated in the Danish National Birth
      Cohort. Information on parental smoking was reported by the mothers during
      pregnancy. Children with ADHD were identified from the Danish Psychiatric Central
      Register, the Danish National Patient Register, and the Register of Medicinal
      Product Statistics by the International Classification of Diseases, 10th Revision
      diagnosis or medication. We also used hyperactivity/inattention score of the
      parent-reported Strengths and Difficulties Questionnaire, included in the 7-year
      follow-up of the National Birth Cohort. RESULTS: Maternal and paternal smoking
      during pregnancy were associated with an elevated risk of ADHD defined by
      hospital diagnosis, medication, and hyperactivity/inattention score, but the
      association was stronger for maternal smoking than for paternal smoking. Compared
      with children born to nonsmoking mothers and smoking fathers, children born of
      smoking mothers and nonsmoking fathers had a higher risk of ADHD (adjusted hazard
      ratio = 1.26; 95% confidence interval, 1.03 to 1.53). We also saw a higher risk
      of ADHD in children of mothers who used nicotine replacement during pregnancy.
      CONCLUSIONS: Our findings indicate that the association between prenatal maternal
      smoking and ADHD may overestimate a causal link, but nicotine exposure or related
      factors may still play a causal role.

PMID- 25049344
TI  - Ambulatory ECMO as a bridge to lung transplant in a previously well pediatric
      patient with ARDS.
AB  - Extracorporeal membrane oxygenation (ECMO) is increasingly implemented in
      patients with end-stage pulmonary disease as a bridge to lung transplant. Several
      centers have instituted an approach that involves physical rehabilitation and
      ambulation for patients supported with ECMO. Recent reports describe the
      successful use of ambulatory ECMO in patients with chronic respiratory illnesses
      being bridged to lung transplant. We describe the first case of a previously
      healthy pediatric patient with acute respiratory failure successfully supported
      with ambulatory ECMO as a bridge to lung transplant after an unsuccessful bridge
      to recovery. Although there are challenges associated with awake and ambulatory
      ECMO in children, this strategy represents an exciting breakthrough and a
      potential paradigm shift in ECMO management for pediatric acute respiratory
      failure. 

PMID- 25049345
TI  - Forging a pediatric primary care-community partnership to support food-insecure
      families.
AB  - BACKGROUND AND OBJECTIVES: Academic primary care clinics often care for children
      from underserved populations affected by food insecurity. Clinical-community
      collaborations could help mitigate such risk. We sought to design, implement,
      refine, and evaluate Keeping Infants Nourished and Developing (KIND), a
      collaborative intervention focused on food-insecure families with infants.
      METHODS: Pediatricians and community collaborators codeveloped processes to link
      food-insecure families with infants to supplementary infant formula, educational
      materials, and clinic and community resources. Intervention evaluation was done
      prospectively by using time-series analysis and descriptive statistics to
      characterize and enumerate those served by KIND during its first 2 years.
      Analyses assessed demographic, clinical, and social risk outcomes, including
      completion of preventive services and referral to social work or our medical
      legal partnership. Comparisons were made between those receiving and not
      receiving KIND by using chi2 statistics. RESULTS: During the 2-year study period,
      1042 families with infants received KIND. Recipients were more likely than
      nonrecipients to have completed a lead test and developmental screen (both P <
      .001), and they were more likely to have received a full set of well-infant
      visits by 14 months (42.0% vs. 28.7%; P < .0001). Those receiving KIND also were
      significantly more likely to have been referred to social work (29.2% vs. 17.6%;
      P < .0001) or the medical-legal partnership (14.8% vs. 5.7%; P < .0001). Weight
      for-length at 9 months did not statistically differ between groups. CONCLUSIONS:
      A clinical-community collaborative enabled pediatric providers to address
      influential social determinants of health. This food insecurity-focused
      intervention was associated with improved preventive care outcomes for the
      infants served.

PMID- 25049346
TI  - ROHHADNET syndrome presenting as major behavioral changes in a 5-year-old obese
      girl.
AB  - Behavioral issues are a frequent problem in the pediatric population. Often,
      these are evaluated and considered to be psychiatric in origin. We report on a
      pediatric patient who presented with severe behavioral disturbance and developed
      organic symptoms including hypoventilation and dysautonomia and who was
      ultimately diagnosed with ROHHADNET syndrome, a syndrome of rapid-onset obesity,
      hypothalamic dysfunction, hypoventilation, and autonomic dysregulation associated
      with a neuroendocrine tumor. Autopsy findings revealed novel findings of the
      syndrome, including hypothalamic encephalitis. 

PMID- 25049347
TI  - Trends in abdominal obesity among U.S. children and adolescents.
AB  - OBJECTIVES: Previous studies showed that prevalence of abdominal obesity among US
      children and adolescents increased significantly between 1988-1994 and 2003-2004.
      However, little is known about recent time trends in abdominal obesity since 2003
      2004.This study was to provide recent updated national estimates of childhood
      abdominal obesity and examine the trends in childhood abdominal obesity from 2003
      to 2012. METHODS: Data were from the National Health and Nutrition Examination
      Survey (NHANES) conducted during 5 time periods (2003-2004, 2005-2006, 2007-2008,
      2009-2010, and 2011-2012). A total of 16,601 US children and adolescents aged 2
      to 18 years were included. Abdominal obesity is defined as a waist circumference
      (WC) >= gender- and age-specific 90th percentile based on data from NHANES III
      (1988-1994) and a waist-to-height (WHtR) >=0.5, respectively. RESULTS: In 2011
      2012, 17.95% of children and adolescents aged 2 to 18 years were abdominally
      obese defined by WC, and 32.93% of those aged 6 to 18 years were abdominally
      obese defined by WHtR. Mean WC and WHtR and prevalence of abdominal obesity kept
      stable between 2003-2004 and 2011-2012, independently of gender, age, and
      race/ethnicity. However, there was a significant decrease in abdominal obesity
      among children aged 2 to 5 years. CONCLUSIONS: The prevalence of abdominal
      obesity leveled off among US children and adolescents from 2003-2004 to 2011
      2012.

PMID- 25049348
TI  - Targeted program for provision of mother's own milk to very low birth weight
      infants.
AB  - OBJECTIVE: Evaluate the effect of an evolving targeted program to encourage
      mothers to provide own milk (MM) to their very low birth weight (VLBW) infants in
      a traditional open-bay NICU. METHODS: Retrospective review of medical records on
      all VLBW infants (birth weight <1500 g) born in a geographical region of Norway
      in 1986/1987, 1996, and 2007/2008 (n = 203). Types of nutrition and data on
      maternal and infant health were prospectively and similarly recorded during all
      time periods. Between each period, targeted programs were initiated to encourage
      provision of MM. RESULTS: The rates of providing MM (exclusively MM in
      parenthesis) for the 3 periods were 55% (33%), 85% (60%), and 89% (62%) when
      achieving full enteral feeds; 48% (11%), 76% (39%), and 92% (60%) at discharge;
      15%, 42%, and 62% at 2 to 4 months' corrected age; and 10%, 40%, and 53% at 6 to
      8 months' corrected age (P < .001 at all end points). Neither maternal or
      pregnancy disorders nor neonatal morbidity had significant effects on provision
      of MM, but smoking was associated with a lower rate after discharge. CONCLUSIONS:
      Both early and long-term provision of MM for their VLBW infants were strongly
      associated with targeted programs to encourage provision. We suggest that almost
      all mothers are able to provide their own milk if given targeted encouragement
      and guidance, even in crowded open-bay NICUs.

PMID- 25049349
TI  - Motor performance after neonatal extracorporeal membrane oxygenation: a
      longitudinal evaluation.
AB  - OBJECTIVE: To assess longitudinally children's motor performance 5 to 12 years
      after neonatal extracorporeal membrane oxygenation (ECMO) and to evaluate
      associations between clinical characteristics and motor performance. METHODS: Two
      hundred fifty-four neonatal ECMO survivors in the Netherlands were tested with
      the Movement Assessment Battery for Children at 5, 8, and/or 12 years. Percentile
      scores were transformed to z scores for longitudinal evaluation (norm population
      mean = 0 and SD = 1). Primary diagnoses: meconium aspiration syndrome (n = 137),
      congenital diaphragmatic hernia (n = 49), persistent pulmonary hypertension of
      the newborn (n = 36), other diagnoses (n = 32). RESULTS: Four hundred fifty-six
      tests were analyzed. At 5, 8, and 12 years motor performance was normal in 73.7,
      74.8, and 40.5%, respectively (vs 85% expected based on reference values; P <
      .001 at all ages). In longitudinal analyses mean (95% confidence interval [CI]) z
      scores were -0.42 (-0.55 to -0.28), -0.25 (-0.40 to -0.10) and -1.00 (-1.26 to 
      0.75) at 5, 8, and 12 years, respectively. Mean score at 8 years was
      significantly higher than at 5 years (difference 0.16, 95% CI 0.02 to 0.30), and
      mean score at 12 years was significantly lower than at both other ages
      (differences -0.59 and -0.75; 95% CI -0.33 to -0.84 and -0.49 to -1.00,
      respectively). Children with congenital diaphragmatic hernia encountered problems
      at all ages. The presence of chronic lung disease was negatively related with
      outcome. CONCLUSIONS: Motor problems in neonatal ECMO survivors persist
      throughout childhood and become more obvious with time.

PMID- 25049350
TI  - Reducing distress in mothers of children with autism and other disabilities: a
      randomized trial.
AB  - BACKGROUND: Compared with other parents, mothers of children with autism spectrum
      disorder or other neurodevelopmental disabilities experience more stress,
      illness, and psychiatric problems. Although the cumulative stress and disease
      burden of these mothers is exceptionally high, and associated with poorer
      outcomes in children, policies and practices primarily serve the identified child
      with disabilities. METHODS: A total of 243 mothers of children with disabilities
      were consented and randomized into either Mindfulness-Based Stress Reduction
      (mindfulness practice) or Positive Adult Development (positive psychology
      practice). Well-trained, supervised peer mentors led 6 weeks of group treatments
      in 1.5-hour weekly sessions, assessing mothers 6 times before, during, and up to
      6 months after treatment. Mothers had children with autism (65%) or other
      disabilities (35%). At baseline, 85% of this community sample had significantly
      elevated stress, 48% were clinically depressed, and 41% had anxiety disorders.
      RESULTS: Using slopes-as-outcomes, mixed random effects models, both treatments
      led to significant reductions in stress, depression, and anxiety, and improved
      sleep and life satisfaction, with large effects in depression and anxiety.
      Mothers in Mindfulness-Based Stress Reduction versus Positive Adult Development
      had greater improvements in anxiety, depression, sleep, and well-being. Mothers
      of children with autism spectrum disorder improved less in anxiety, but did not
      otherwise differ from their counterparts. CONCLUSIONS: Future studies are
      warranted on how trained mentors and professionals can address the unmet mental
      health needs of mothers of children with developmental disabilities. Doing so
      improves maternal well-being and furthers their long-term caregiving of children
      with complex developmental, physical, and behavioral needs.

PMID- 25049352
TI  - The natural history of jaundice in predominantly breastfed infants.
AB  - BACKGROUND AND OBJECTIVES: Breastfed newborns are more likely to develop
      prolonged hyperbilirubinemia than those fed formula, but the prevalence of
      prolonged hyperbilirubinemia in a largely white, North American breastfed
      population is unknown. In this population, we documented the natural history of
      jaundice and the prevalence of prolonged hyperbilirubinemia, and we evaluated the
      utility of assessing the cephalocaudal progression of jaundice in office-based
      practices. METHODS: We measured transcutaneous bilirubin (TcB) levels during the
      first month in 1044 predominantly breastfed infants >=35 weeks of gestation and
      assigned a cephalocaudal zone score to each infant at the time of the TcB
      measurement. RESULTS: TcB level was >=5 mg/dL in 43% of infants at age 21 +/- 3
      days and 34% were clinically jaundiced. At 28 +/- 3 days, the TcB was >=5 mg/dL
      in 34% and 21% were jaundiced. There was a strong correlation between the TcB
      level and the jaundice zone score, but there was a wide range of TcB levels
      associated with each score. CONCLUSIONS: Practitioners can be reassured that it
      is normal for 20% to 30% of predominantly breastfed newborns to be jaundiced at
      age 3 to 4 weeks and for 30% to 40% of these infants to have bilirubin levels >=5
      mg/dL. The jaundice zone score does not provide an accurate assessment of the
      bilirubin level, but a score of zero (complete absence of jaundice) suggests that
      the level is unlikely to be >12.9 mg/dL, whereas a score of >=4 usually predicts
      a level of >=10 mg/dL.

PMID- 25049351
TI  - Maternal obesity in pregnancy, gestational weight gain, and risk of childhood
      asthma.
AB  - BACKGROUND AND OBJECTIVE: Environmental or lifestyle exposures in utero may
      influence the development of childhood asthma. In this meta-analysis, we aimed to
      assess whether maternal obesity in pregnancy (MOP) or increased maternal
      gestational weight gain (GWG) increased the risk of asthma in offspring. METHODS:
      We included all observational studies published until October 2013 in PubMed,
      Embase, CINAHL, Scopus, The Cochrane Database, and Ovid. Random effects models
      with inverse variance weights were used to calculate pooled risk estimates.
      RESULTS: Fourteen studies were included (N = 108 321 mother-child pairs). Twelve
      studies reported maternal obesity, and 5 reported GWG. Age of children was 14
      months to 16 years. MOP was associated with higher odds of asthma or wheeze ever
      (OR = 1.31; 95% confidence interval [CI], 1.16-1.49) or current (OR = 1.21; 95%
      CI, 1.07-1.37); each 1-kg/m(2) increase in maternal BMI was associated with a 2%
      to 3% increase in the odds of childhood asthma. High GWG was associated with
      higher odds of asthma or wheeze ever (OR = 1.16; 95% CI, 1.001-1.34). Maternal
      underweight and low GWG were not associated with childhood asthma or wheeze. Meta
      regression showed a negative association of borderline significance for maternal
      asthma history (P = .07). The significant heterogeneity among existing studies
      indicates a need for standardized approaches to future studies on the topic.
      CONCLUSIONS: MOP and high GWG are associated with an elevated risk of childhood
      asthma; this finding may be particularly significant for mothers without asthma
      history. Prospective randomized trials of maternal weight management are needed.

PMID- 25049353
TI  - "It makes me feel like myself": Person-centered versus traditional visual arts
      activities for people with dementia.
AB  - During a 15-month period between February 2010 and April 2011, video data on (n =
      38) people with dementia were collected during a person-centered and
      intergenerational arts activity program called Opening Minds through Art (OMA) at
      three different long-term care facilities in Ohio. A subsample of the OMA
      participants (n = 10) were also video recorded during traditional visual arts
      activities (e.g. coloring books, scrapbooking). A modified version of the Greater
      Cincinnati Chapter Well-Being Observation Tool(c) was used to code the intensity
      and frequency of observed domains of well-being (i.e. social interest,
      engagement, and pleasure) and ill-being (i.e. disengagement, negative affect,
      sadness, and confusion). Descriptive results indicate a high percentage of
      moderate or high intensities of well-being during OMA sessions with little to no
      ill-being. Paired-sample t-tests comparing OMA vs. traditional visual arts
      activities showed significantly higher intensity scores for OMA in the domain of
      engagement and pleasure, as well as significantly lower intensity scores for
      disengagement. The findings of this exploratory study contribute to the overall
      discussion about the impact of person-centered, creative-expressive arts
      activities on people with dementia. 

PMID- 25049354
TI  - Matrix metalloproteinase-8 plays a pivotal role in neuroinflammation by
      modulating TNF-alpha activation.
AB  - Matrix metalloproteinases (MMPs) play important roles in normal brain development
      and synaptic plasticity, although aberrant expression of MMPs leads to brain
      damage, including blood-brain barrier disruption, inflammation, demyelination,
      and neuronal cell death. In this article, we report that MMP-8 is upregulated in
      LPS-stimulated BV2 microglial cells and primary cultured microglia, and treatment
      of MMP-8 inhibitor (M8I) or MMP-8 short hairpin RNA suppresses proinflammatory
      molecules, particularly TNF-alpha secretion. Subsequent experiments showed that
      MMP-8 exhibits TNF-alpha-converting enzyme (TACE) activity by cleaving the
      prodomain of TNF-alpha (A(74)/Q(75), A(76)/V(77) residues) and, furthermore, that
      M8I inhibits TACE activity more efficiently than TAPI-0, a general TACE
      inhibitor. Biochemical analysis of the underlying anti-inflammatory mechanisms of
      M8I revealed that it inhibits MAPK phosphorylation, NF-kappaB/AP-1 activity, and
      reactive oxygen species production. Further support for the proinflammatory role
      of microglial MMP-8 was obtained from an in vivo animal model of
      neuroinflammatory disorder. MMP-8 is upregulated in septic conditions,
      particularly in microglia. Administration of M8I or MMP-8 short hairpin RNA
      significantly inhibits microglial activation and expression/secretion of TNF
      alpha in brain tissue, serum, and cerebrospinal fluid of LPS-induced septic mice.
      These results demonstrate that MMP-8 critically mediates microglial activation by
      modulating TNF-alpha activity, which may explain neuroinflammation in septic
      mouse brain. 

PMID- 25049355
TI  - Neutrophils mediate blood-spinal cord barrier disruption in demyelinating
      neuroinflammatory diseases.
AB  - Disruption of the blood-brain and blood-spinal cord barriers (BBB and BSCB,
      respectively) and immune cell infiltration are early pathophysiological hallmarks
      of multiple sclerosis (MS), its animal model experimental autoimmune
      encephalomyelitis (EAE), and neuromyelitis optica (NMO). However, their
      contribution to disease initiation and development remains unclear. In this
      study, we induced EAE in lys-eGFP-ki mice and performed single, nonterminal
      intravital imaging to investigate BSCB permeability simultaneously with the
      kinetics of GFP(+) myeloid cell infiltration. We observed a loss in BSCB
      integrity within a day of disease onset, which paralleled the infiltration of
      GFP(+) cells into the CNS and lasted for ~4 d. Neutrophils accounted for a
      significant proportion of the circulating and CNS-infiltrating myeloid cells
      during the preclinical phase of EAE, and their depletion delayed the onset and
      reduced the severity of EAE while maintaining BSCB integrity. We also show that
      neutrophils collected from the blood or bone marrow of EAE mice transmigrate more
      efficiently than do neutrophils of naive animals in a BBB cell culture model.
      Moreover, using intravital videomicroscopy, we demonstrate that the IL-1R type 1
      governs the firm adhesion of neutrophils to the inflamed spinal cord vasculature.
      Finally, immunostaining of postmortem CNS material obtained from an acutely ill
      multiple sclerosis patient and two neuromyelitis optica patients revealed
      instances of infiltrated neutrophils associated with regions of BBB or BSCB
      leakage. Taken together, our data provide evidence that neutrophils are involved
      in the initial events that take place during EAE and that they are intimately
      linked with the status of the BBB/BSCB. 

PMID- 25049356
TI  - Prostaglandin E2 negatively regulates the production of inflammatory
      cytokines/chemokines and IL-17 in visceral leishmaniasis.
AB  - Persistence of intracellular infection depends on the exploitation of factors
      that negatively regulate the host immune response. In this study, we elucidated
      the role of macrophage PGE2, an immunoregulatory lipid, in successful survival of
      Leishmania donovani, causative agent of the fatal visceral leishmaniasis. PGE2
      production was induced during infection and resulted in increased cAMP level in
      peritoneal macrophages through G protein-coupled E-series prostanoid (EP)
      receptors. Among four different EPs (EP1-4), infection upregulated the expression
      of only EP2, and individual administration of either EP2-specific agonist,
      butaprost, or 8-Br-cAMP, a cell-permeable cAMP analog, promoted parasite
      survival. Inhibition of cAMP also induced generation of reactive oxygen species,
      an antileishmanial effector molecule. Negative modulation of PGE2 signaling
      reduced infection-induced anti-inflammatory cytokine polarization and enhanced
      inflammatory chemokines, CCL3 and CCL5. Effect of PGE2 on cytokine and chemokine
      production was found to be differentially modulated by cAMP-dependent protein
      kinase A (PKA) and exchange protein directly activated by cAMP (EPAC). PGE2
      induced decreases in TNF-alpha and CCL5 were mediated specifically by PKA,
      whereas administration of brefeldin A, an EPAC inhibitor, could reverse decreased
      production of CCL3. Apart from modulating inflammatory/anti-inflammatory balance,
      PGE2 inhibited antileishmanial IL-17 cytokine production in splenocyte culture.
      Augmented PGE2 production was also found in splenocytes of infected mice, and
      administration of EP2 antagonist in mice resulted in reduced liver and spleen
      parasite burden along with host-favorable T cell response. These results suggest
      that Leishmania facilitates an immunosuppressive environment in macrophages by
      PGE2-driven, EP2-mediated cAMP signaling that is differentially regulated by PKA
      and EPAC. 

PMID- 25049357
TI  - PTX3 binds MD-2 and promotes TRIF-dependent immune protection in aspergillosis.
AB  - The long pentraxin 3 (PTX3) modulates different effector pathways involved in
      innate resistance to Aspergillus fumigatus, including complement activation or
      promotion of phagocytosis by interacting with FcgammaRs. However, whether and how
      TLRs modulate PTX3 mediates antifungal resistance is not known. In this study, we
      demonstrate that PTX3 binds myeloid differentiation protein 2 (MD-2) in vitro and
      exerts its protective antifungal activity in vivo through TLR4/MD-2-mediated
      signaling. Similar to Tlr4(-/-) mice, Md2(-/-) mice displayed high susceptibility
      to pulmonary aspergillosis, a phenotype associated with a proinflammatory
      cytokine profile and impaired antifungal activity of polymorphonuclear
      neutrophils. Treating Md2(-/-) mice with PTX3 failed to confer immune protection
      against the fungus, whereas adoptive transfer of MD-2-competent polymorphonuclear
      neutrophils restored it. Mechanistically, engagement of MD-2 by PTX3-opsonized
      Aspergillus conidia activated the TLR4/Toll/IL-1R domain-containing adapter
      inducing IFN-beta-dependent signaling pathway converging on IL-10. Thus, we have
      identified a novel receptor mechanism, involving the TLR4/MD-2/Toll/IL-1R domain
      containing adapter inducing IFN-beta-mediated signaling, whereby PTX3 elicits
      antifungal resistance with limited immunopathology in A. fumigatus infection. 

PMID- 25049358
TI  - Vector-encoded Helicobacter pylori neutrophil-activating protein promotes
      maturation of dendritic cells with Th1 polarization and improved migration.
AB  - Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence
      factor involved in H. pylori infection. Both HP-NAP protein and oncolytic viruses
      encoding HP-NAP have been suggested as immunotherapeutic anticancer agents and
      adjuvants for vaccination but with little known about its mode of action to
      activate adaptive immunity. Dendritic cells (DCs) are key players in bridging
      innate and adaptive immune responses, and in this study we aim to evaluate the
      effect of HP-NAP on DC maturation, migration, and induction of adaptive immune
      response. Maturation markers CD83, CD80, CD86, HLA-DR, CD40, and CCR7 were
      upregulated on human DCs after treatment with supernatants from HP-NAP adenovirus
      infected cells. HP-NAP-activated DCs had a Th1 cytokine secretion profile, with
      high IL-12 and relatively low IL-10 secretion, and migrated toward CCL19. Ag
      specific T cells were efficiently expanded by Ag-presenting HP-NAP-activated DCs,
      which is an important property of functionally mature DCs. Furthermore,
      intradermal injections of HP-NAP-encoding adenovirus in C57BL/6 mice enhanced
      resident DC migration to draining lymph nodes, which was verified by imaging
      lymph nodes by two-photon microscopy and by phenotyping migrating cells by flow
      cytometry. In conclusion, therapeutic effects of HP-NAP are mediated by
      maturation of DCs and subsequent activation of Ag-specific T cells in addition to
      provoking innate immunity. 

PMID- 25049359
TI  - GM-CSF-neuroantigen fusion proteins reverse experimental autoimmune
      encephalomyelitis and mediate tolerogenic activity in adjuvant-primed
      environments: association with inflammation-dependent, inhibitory antigen
      presentation.
AB  - Single-chain fusion proteins comprised of GM-CSF and neuroantigen (NAg) are
      potent, NAg-specific inhibitors of experimental autoimmune encephalomyelitis
      (EAE). An important question was whether GMCSF-NAg tolerogenic vaccines retained
      inhibitory activity within inflammatory environments or were contingent upon
      steady-state conditions. GM-CSF fused to the myelin oligodendrocyte glycoprotein
      MOG35-55 peptide (GMCSF-MOG) reversed established paralytic disease in both
      passive and active models of EAE in C57BL/6 mice. The fusion protein also
      reversed EAE in CD4-deficient and B cell-deficient mice. Notably, GMCSF-MOG
      inhibited EAE when coinjected adjacent to the MOG35-55/CFA emulsion. GMCSF-MOG
      also retained dominant inhibitory activity when directly emulsified with MOG35-55
      in the CFA emulsion in both C57BL/6 or B cell-deficient models of EAE. Likewise,
      when combined with proteolipid protein 139-151 in CFA, GM-CSF fused to
      proteolipid protein 139-151 peptide inhibited EAE in SJL mice. When deliberately
      emulsified in CFA with the NAg, GMCSF-NAg inhibited EAE even though NAg was
      present at >30-fold molar excess. In vitro studies revealed that the GM-CSF
      domain of GMCSF-MOG stimulated growth and differentiation of inflammatory
      dendritic cells (DC) and simultaneously targeted the MOG35-55 domain for enhanced
      presentation by these DC. These inflammatory DC presented MOG35-55 to MOG
      specific T cells by an inhibitory mechanism that was mediated in part by IFN
      gamma signaling and NO production. In conclusion, GMCSF-NAg was tolerogenic in
      CFA-primed proinflammatory environments by a mechanism associated with targeted
      Ag presentation by inflammatory DC and an inhibitory IFN-gamma/NO pathway. The
      inhibitory activity of GMCSF-NAg in CFA-primed lymphatics distinguishes GMCSF-NAg
      fusion proteins as a unique class of inflammation-dependent tolerogens that are
      mechanistically distinct from naked peptide or protein-based tolerogens. 

PMID- 25049360
TI  - Dissection of the control of anion homeostasis by associative transcriptomics in
      Brassica napus.
AB  - To assess the variation in nutrient homeostasis in oilseed rape and to identify
      the genes responsible for this variation, we determined foliar anion levels in a
      diversity panel of Brassica napus accessions, 84 of which had been genotyped
      previously using messenger RNA sequencing. We applied associative transcriptomics
      to identify sequence polymorphisms linked to variation in nitrate, phosphate, or
      sulfate in these accessions. The analysis identified several hundred significant
      associations for each anion. Using functional annotation of Arabidopsis
      (Arabidopsis thaliana) homologs and available microarray data, we identified 60
      candidate genes for controlling variation in the anion contents. To verify that
      these genes function in the control of nutrient homeostasis, we obtained
      Arabidopsis transfer DNA insertion lines for these candidates and tested them for
      the accumulation of nitrate, phosphate, and sulfate. Fourteen lines differed
      significantly in levels of the corresponding anions. Several of these genes have
      been shown previously to affect the accumulation of the corresponding anions in
      Arabidopsis mutants. These results thus confirm the power of associative
      transcriptomics in dissection of the genetic control of complex traits and
      present a set of candidate genes for use in the improvement of efficiency of B.
      napus mineral nutrition. 

PMID- 25049361
TI  - ASCORBATE PEROXIDASE6 protects Arabidopsis desiccating and germinating seeds from
      stress and mediates cross talk between reactive oxygen species, abscisic acid,
      and auxin.
AB  - A seed's ability to properly germinate largely depends on its oxidative poise.
      The level of reactive oxygen species (ROS) in Arabidopsis (Arabidopsis thaliana)
      is controlled by a large gene network, which includes the gene coding for the
      hydrogen peroxide-scavenging enzyme, cytosolic ASCORBATE PEROXIDASE6 (APX6), yet
      its specific function has remained unknown. In this study, we show that seeds
      lacking APX6 accumulate higher levels of ROS, exhibit increased oxidative damage,
      and display reduced germination on soil under control conditions and that these
      effects are further exacerbated under osmotic, salt, or heat stress. In addition,
      ripening APX6-deficient seeds exposed to heat stress displayed reduced
      germination vigor. This, together with the increased abundance of APX6 during
      late stages of maturation, indicates that APX6 activity is critical for the
      maturation-drying phase. Metabolic profiling revealed an altered activity of the
      tricarboxylic acid cycle, changes in amino acid levels, and elevated metabolism
      of abscisic acid (ABA) and auxin in drying apx6 mutant seeds. Further germination
      assays showed an impaired response of the apx6 mutants to ABA and to indole-3
      acetic acid. Relative suppression of abscisic acid insensitive3 (ABI3) and ABI5
      expression, two of the major ABA signaling downstream components controlling
      dormancy, suggested that an alternative signaling route inhibiting germination
      was activated. Thus, our study uncovered a new role for APX6, in protecting
      mature desiccating and germinating seeds from excessive oxidative damage, and
      suggested that APX6 modulate the ROS signal cross talk with hormone signals to
      properly execute the germination program in Arabidopsis. 

PMID- 25049363
TI  - Risk of needlestick injury in the use of plastic bottles as containers for needle
      disposal.

PMID- 25049362
TI  - bHLH05 is an interaction partner of MYB51 and a novel regulator of glucosinolate
      biosynthesis in Arabidopsis.
AB  - By means of yeast (Saccharomyces cerevisiae) two-hybrid screening, we identified
      basic helix-loop-helix transcription factor05 (bHLH05) as an interacting partner
      of MYB51, the key regulator of indolic glucosinolates (GSLs) in Arabidopsis
      (Arabidopsis thaliana). Furthermore, we show that bHLH04, bHLH05, and bHLH06/MYC2
      also interact with other R2R3-MYBs regulating GSL biosynthesis. Analysis of bhlh
      loss-of-function mutants revealed that the single bhlh mutants retained GSL
      levels that were similar to those in wild-type plants, whereas the triple
      bhlh04/05/06 mutant was depleted in the production of GSL. Unlike bhlh04/06 and
      bhlh05/06 mutants, the double bhlh04/05 mutant was strongly affected in the
      production of GSL, pointing to a special role of bHLH04 and bHLH05 in the control
      of GSL levels in the absence of jasmonic acid. The combination of two specific
      gain-of-function alleles of MYB and bHLH proteins had an additive effect on GSL
      levels, as demonstrated by the analysis of the double MYB34-1D bHLH05D94N mutant,
      which produces 20-fold more indolic GSLs than bHLH05D94N and ecotype Columbia-0
      of Arabidopsis. The amino acid substitution D94N in bHLH05D94N negatively affects
      the interaction with JASMONATE-ZIM DOMAIN protein, thereby resulting in
      constitutive activation of bHLH05 and mimicking jasmonic acid treatment. Our
      study revealed the bHLH04, bHLH05, and bHLH06/MYC2 factors as novel regulators of
      GSL biosynthesis in Arabidopsis. 

PMID- 25049364
TI  - Novel insulin delivery profiles for mixed meals for sensor-augmented pump and
      closed-loop artificial pancreas therapy for type 1 diabetes mellitus.
AB  - Maintaining euglycemia for people with type 1 diabetes is highly challenging, and
      variations in glucose absorption rates with meal composition require meal type
      specific insulin delivery profiles for optimal blood glucose control. Traditional
      basal/bolus therapy is not fully optimized for meals of varied fat contents.
      Thus, regimens for low- and high-fat meals were developed to improve current
      insulin pump therapy. Simulations of meals with varied fat content demonstrably
      replicated published data. Subsequently, an insulin profile library with
      optimized delivery regimens under open and closed loop for various meal
      compositions was constructed using particle swarm optimization. Calculations
      showed that the optimal basal bolus insulin profiles for low-fat meals comprise a
      normal bolus or a short wave. The preferred delivery for high-fat meals is
      typically biphasic, but can extend to multiple phases depending on meal
      characteristics. Results also revealed that patients that are highly sensitive to
      insulin could benefit from biphasic deliveries. Preliminary investigations of the
      optimal closed-loop regimens also display bi- or multiphasic patterns for high
      fat meals. The novel insulin delivery profiles present new waveforms that provide
      better control of postprandial glucose excursions than existing schemes.
      Furthermore, the proposed novel regimens are also more or similarly robust to
      uncertainties in meal parameter estimates, with the closed-loop schemes
      demonstrating superior performance and robustness. 

PMID- 25049366
TI  - Professional Success and Gender in Family Medicine: Design of Scales and
      Examination of Gender Differences in Subjective and Objective Success Among
      Family Physicians.
AB  - Two components of professional success have been defined: objective career
      success (OCS) and subjective career success (SCS). Despite the increasing number
      of women practicing medicine, gender inequalities persist. The objectives of this
      descriptive, cross-sectional, and multicenter study were (a) to construct and
      validate OCS and SCS scales, (b) to determine the relationships between OCS and
      SCS and between each scale and professional/family characteristics, and (c) to
      compare these associations between male and female family physicians (FPs). The
      study sample comprised 250 female and 250 male FPs from urban health centers in
      Andalusia (Spain). Data were gathered over 6 months on gender, age, care load,
      professional/family variables, and family-work balance, using a self-administered
      questionnaire. OSC and SCS scales were examined by using exploratory factorial
      analysis and Cronbach's alpha, and scores were compared by gender-stratified
      bivariate and multiple regression analyses. Intraclass correlation coefficients
      were calculated using a multilevel analysis. The response rate was 73.6%. We
      identified three OCS factors and two SCS factors. Lower scores were obtained by
      female versus male FPs in the OCS dimensions, but there were no gender
      differences in either SCS dimension. 

PMID- 25049365
TI  - Fault detection and safety in closed-loop artificial pancreas systems.
AB  - Continuous subcutaneous insulin infusion pumps and continuous glucose monitors
      enable individuals with type 1 diabetes to achieve tighter blood glucose control
      and are critical components in a closed-loop artificial pancreas. Insulin
      infusion sets can fail and continuous glucose monitor sensor signals can suffer
      from a variety of anomalies, including signal dropout and pressure-induced sensor
      attenuations. In addition to hardware-based failures, software and human-induced
      errors can cause safety-related problems. Techniques for fault detection, safety
      analyses, and remote monitoring techniques that have been applied in other
      industries and applications, such as chemical process plants and commercial
      aircraft, are discussed and placed in the context of a closed-loop artificial
      pancreas.

PMID- 25049367
TI  - Surgical relocation of peroneal tendon dislocation with calcaneal open reduction
      and internal fixation: technique tip.

PMID- 25049368
TI  - Return to duty after elective fasciotomy for chronic exertional compartment
      syndrome.
AB  - BACKGROUND: Civilian literature has reported excellent outcomes after elective
      fasciotomy for chronic exertional compartment syndrome (CECS). Our study's
      purpose was to objectively investigate the functional outcome of fasciotomies
      performed for CECS in a high demand military population. METHODS: A retrospective
      review of all fasciotomies performed for CECS at a single tertiary military
      medical center was performed. The primary outcome measure was the ability to
      return to full active duty. Diagnosis, operative technique, and number of
      compartments addressed were collected and analyzed. Patients were contacted and
      the visual analog scale (VAS) pain score, functional single assessment numeric
      evaluation (SANE) score, as well as overall satisfaction were reported. Return to
      duty status was collected on 70 of 70 (100%) consecutive operative extremities in
      46 patients with an average follow-up of 26 months. RESULTS: Only 19 patients
      (41.3%) were able to return to full active duty. Ten patients (21.7%) underwent a
      medical separation from the military and 17 patients (37%) remained in the
      military but were on restricted duty secondary to persistent leg pain. Thirty
      five of 46 (76%) of the patients were contacted and provided subjective feedback.
      The average SANE score was 72.3, and there was a mean improvement of 4.4 points
      in VAS score postoperatively. Overall, 71% of patients were satisfied and would
      undergo the procedure again. Outcomes were correlated to operative technique,
      patient rank, and branch of military service. CONCLUSION: Our study showed a
      return to full military duty in 41% of patients who underwent elective fasciotomy
      for CECS. Overall 78% of patients remained in the military, which is consistent
      with previous military literature. Subjective satisfaction rate was 71%. Both the
      return to activity and subjective outcomes in our study population were
      substantially lower than reported results in civilian populations. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 25049371
TI  - Revised Manuscript Submission Guidelines.

PMID- 25049372
TI  - Spatial Access to Faith-based Diabetes Intervention for Guyanese Adults in
      Schenectady, New York.
AB  - PURPOSE: The purpose of this study is to examine whether travel distance would
      pose a barrier to participation in proposed diabetes intervention programs for
      Guyanese immigrants at faith-based organizations (FBOs). This study also suggests
      the most collectively accessible set of FBOs that could serve as intervention
      sites. METHODS: Data were extracted from a cross-sectional health interview
      survey conducted in Schenectady, New York, in 2011. The shortest driving
      distances from homes to FBOs and to the city's only diabetes education center
      (DEC) were analyzed among Guyanese and non-Guyanese adults with diabetes and
      prediabetes (n = 238), using spatial algorithms and Geographic Information System
      resources. RESULTS: The Guyanese were more likely to belong to a FBO than the non
      Guyanese (77.8% vs 61.2%). The mean driving distance to FBO was 1.19 miles (95%
      CI, 0.98-1.39) for the Guyanese, which was significantly shorter than that for
      the non-Guyanese (2.87 miles, 95% CI, 1.93-3.82). The Guyanese had uniformly
      shorter mean and median driving distances in all sociodemographic and health
      status subcategories as well. Moreover, a higher percentage of the Guyanese lived
      closer to FBO than to DEC compared to non-Guyanese (52.2% vs 34.7%). It was found
      that having diabetes intervention at the 4 most popular FBOs (2 Hindu temples and
      2 Christian churches) and DEC would provide the most collectively accessible
      arrangement for the Guyanese. CONCLUSIONS: The results suggest that the short
      driving distance to FBO is a likely enabler that can encourage regular
      utilization of the faith-based intervention for the Guyanese.

PMID- 25049375
TI  - Minor amputation and palliative wound care as a strategy to avoid major
      amputation in patients with foot infections and severe peripheral arterial
      disease.
AB  - Foot infections occurring in patients with severe peripheral arterial disease
      (PAD) who are not considered candidates for revascularization and limb salvage
      efforts are generally treated with major amputations. Herein we describe our
      early experiences in managing foot infections with minor amputations and
      palliative wound care as a strategy to avoid the functional disability often
      associated with major amputations. Patients with severe PAD that underwent minor
      amputations and subsequent palliative wound care for moderate/severe infections
      were paired with age-matched controls with PAD that underwent primary major
      amputations for foot infections. Eleven patients who underwent minor amputations
      and palliative wound care of 13 limbs were compared to an age-matched cohort of
      12 patients undergoing 13 major amputations.The median age was 80 years in both
      groups. Survival at 1 and 2 years did not differ significantly between groups.
      All patients who were ambulatory and/or independently living remained so
      following palliative management; in contrast, major amputation changed ambulatory
      status in 75% of patients and independent living status in 50%. Palliative
      management did not result in ascending/systemic sepsis or progressive necrosis.
      The need for reoperations was uncommon in both groups. In summary, minor
      amputations and operative drainage with subsequent palliative wound care appears
      to be a safe management option in patients with severe PAD and moderate or severe
      foot infections that are not candidates for revascularization. Palliative
      management may result in less functional impairment than major amputation. 

PMID- 25049376
TI  - Predicting fruit fly's sensing rate with insect flight simulations.
AB  - Without sensory feedback, flies cannot fly. Exactly how various feedback controls
      work in insects is a complex puzzle to solve. What do insects measure to
      stabilize their flight? How often and how fast must insects adjust their wings to
      remain stable? To gain insights into algorithms used by insects to control their
      dynamic instability, we develop a simulation tool to study free flight. To
      stabilize flight, we construct a control algorithm that modulates wing motion
      based on discrete measurements of the body-pitch orientation. Our simulations
      give theoretical bounds on both the sensing rate and the delay time between
      sensing and actuation. Interpreting our findings together with experimental
      results on fruit flies' reaction time and sensory motor reflexes, we conjecture
      that fruit flies sense their kinematic states every wing beat to stabilize their
      flight. We further propose a candidate for such a control involving the fly's
      haltere and first basalar motor neuron. Although we focus on fruit flies as a
      case study, the framework for our simulation and discrete control algorithms is
      applicable to studies of both natural and man-made fliers. 

PMID- 25049377
TI  - Type-I interferon signaling through ISGF3 complex is required for sustained Rip3
      activation and necroptosis in macrophages.
AB  - Myeloid cells play a critical role in perpetuating inflammation during various
      chronic diseases. Recently the death of macrophages through programmed necrosis
      (necroptosis) has emerged as an important mechanism in inflammation and
      pathology. We evaluated the mechanisms that lead to the induction of necrotic
      cell death in macrophages. Our results indicate that type I IFN (IFN-I) signaling
      is a predominant mechanism of necroptosis, because macrophages deficient in IFN
      alpha receptor type I (IFNAR1) are highly resistant to necroptosis after
      stimulation with LPS, polyinosinic-polycytidylic acid, TNF-alpha, or IFN-beta in
      the presence of caspase inhibitors. IFN-I-induced necroptosis occurred through
      both mechanisms dependent on and independent of Toll/IL-1 receptor domain
      containing adaptor inducing IFN-beta (TRIF) and led to persistent phosphorylation
      of receptor-interacting protein 3 (Rip3) kinase, which resulted in potent
      necroptosis. Although various IFN-regulatory factors (IRFs) facilitated the
      induction of necroptosis in response to IFN-beta, IRF-9-STAT1- or -STAT2
      deficient macrophages were highly resistant to necroptosis. Our results indicate
      that IFN-beta-induced necroptosis of macrophages proceeds through tonic IFN
      stimulated gene factor 3 (ISGF3) signaling, which leads to persistent expression
      of STAT1, STAT2, and IRF9. Induction of IFNAR1/Rip3-dependent necroptosis also
      resulted in potent inflammatory pathology in vivo. These results reveal how IFN-I
      mediates acute inflammation through macrophage necroptosis. 

PMID- 25049378
TI  - Harmonization of initial estimates of shale gas life cycle greenhouse gas
      emissions for electric power generation.
AB  - Recent technological advances in the recovery of unconventional natural gas,
      particularly shale gas, have served to dramatically increase domestic production
      and reserve estimates for the United States and internationally. This trend has
      led to lowered prices and increased scrutiny on production practices. Questions
      have been raised as to how greenhouse gas (GHG) emissions from the life cycle of
      shale gas production and use compares with that of conventionally produced
      natural gas or other fuel sources such as coal. Recent literature has come to
      different conclusions on this point, largely due to differing assumptions,
      comparison baselines, and system boundaries. Through a meta-analytical procedure
      we call harmonization, we develop robust, analytically consistent, and updated
      comparisons of estimates of life cycle GHG emissions for electricity produced
      from shale gas, conventionally produced natural gas, and coal. On a per-unit
      electrical output basis, harmonization reveals that median estimates of GHG
      emissions from shale gas-generated electricity are similar to those for
      conventional natural gas, with both approximately half that of the central
      tendency of coal. Sensitivity analysis on the harmonized estimates indicates that
      assumptions regarding liquids unloading and estimated ultimate recovery (EUR) of
      wells have the greatest influence on life cycle GHG emissions, whereby shale gas
      life cycle GHG emissions could approach the range of best-performing coal-fired
      generation under certain scenarios. Despite clarification of published estimates
      through harmonization, these initial assessments should be confirmed through
      methane emissions measurements at components and in the atmosphere and through
      better characterization of EUR and practices. 

PMID- 25049379
TI  - Blockade of oncogenic IkappaB kinase activity in diffuse large B-cell lymphoma by
      bromodomain and extraterminal domain protein inhibitors.
AB  - In the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma
      (DLBCL), NF-kappaB activity is essential for viability of the malignant cells and
      is sustained by constitutive activity of IkappaB kinase (IKK) in the cytoplasm.
      Here, we report an unexpected role for the bromodomain and extraterminal domain
      (BET) proteins BRD2 and BRD4 in maintaining oncogenic IKK activity in ABC DLBCL.
      IKK activity was reduced by small molecules targeting BET proteins as well as by
      genetic knockdown of BRD2 and BRD4 expression, thereby inhibiting downstream NF
      kappaB-driven transcriptional programs and killing ABC DLBCL cells. Using a high
      throughput platform to screen for drug-drug synergy, we observed that the BET
      inhibitor JQ1 combined favorably with multiple drugs targeting B-cell receptor
      signaling, one pathway that activates IKK in ABC DLBCL. The BTK kinase inhibitor
      ibrutinib, which is in clinical development for the treatment of ABC DLBCL,
      synergized strongly with BET inhibitors in killing ABC DLBCL cells in vitro and
      in a xenograft mouse model. These findings provide a mechanistic basis for the
      clinical development of BET protein inhibitors in ABC DLBCL, particularly in
      combination with other modulators of oncogenic IKK signaling. 

PMID- 25049380
TI  - Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted,
      polymer-based nanoparticle containing siRNA.
AB  - Nanoparticle-based experimental therapeutics are currently being investigated in
      numerous human clinical trials. CALAA-01 is a targeted, polymer-based
      nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was
      the first RNA interference (RNAi)-based, experimental therapeutic to be
      administered to cancer patients. Here, we report the results from the initial
      phase I clinical trial where 24 patients with different cancers were treated with
      CALAA-01 and compare those results to data obtained from multispecies animal
      studies to provide a detailed example of translating this class of nanoparticles
      from animals to humans. The pharmacokinetics of CALAA-01 in mice, rats, monkeys,
      and humans show fast elimination and reveal that the maximum concentration
      obtained in the blood after i.v. administration correlates with body weight
      across all species. The safety profile of CALAA-01 in animals is similarly
      obtained in humans except that animal kidney toxicities are not observed in
      humans; this could be due to the use of a predosing hydration protocol used in
      the clinic. Taken in total, the animal models do appear to predict the behavior
      of CALAA-01 in humans. 

PMID- 25049381
TI  - Sequence-resolved free energy profiles of stress-bearing vimentin intermediate
      filaments.
AB  - Intermediate filaments (IFs) are key to the mechanical strength of metazoan
      cells. Their basic building blocks are dimeric coiled coils mediating
      hierarchical assembly of the full-length filaments. Here we use single-molecule
      force spectroscopy by optical tweezers to assess the folding and stability of
      coil 2B of the model IF protein vimentin. The coiled coil was unzipped from its N
      and C termini. When pulling from the C terminus, we observed that the coiled coil
      was resistant to force owing to the high stability of the C-terminal region.
      Pulling from the N terminus revealed that the N-terminal half is considerably
      less stable. The mechanical pulling assay is a unique tool to study and control
      seed formation and structure propagation of the coiled coil. We then used
      rigorous theory-based deconvolution for a model-free extraction of the energy
      landscape and local stability profiles. The data obtained from the two distinct
      pulling directions complement each other and reveal a tripartite stability of the
      coiled coil: a labile N-terminal half, followed by a medium stability section and
      a highly stable region at the far C-terminal end. The different stability regions
      provide important insight into the mechanics of IF assembly. 

PMID- 25049382
TI  - Population of sensory neurons essential for asthmatic hyperreactivity of inflamed
      airways.
AB  - Asthma is a common debilitating inflammatory lung disease affecting over 200
      million people worldwide. Here, we investigated neurogenic components involved in
      asthmatic-like attacks using the ovalbumin-sensitized murine model of the
      disease, and identified a specific population of neurons that are required for
      airway hyperreactivity. We show that ablating or genetically silencing these
      neurons abolished the hyperreactive broncho-constrictions, even in the presence
      of a fully developed lung inflammatory immune response. These neurons are found
      in the vagal ganglia and are characterized by the expression of the transient
      receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel
      itself is not required for the asthmatic-like hyperreactive airway response. We
      also demonstrate that optogenetic stimulation of this population of TRP
      expressing cells with channelrhodopsin dramatically exacerbates airway
      hyperreactivity of inflamed airways. Notably, these cells express the sphingosine
      1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently
      induced broncho-constrictions, even in the absence of ovalbumin sensitization and
      inflammation. Our results show that the airway hyperreactivity phenotype can be
      physiologically dissociated from the immune component, and provide a platform for
      devising therapeutic approaches to asthma that target these pathways separately. 

PMID- 25049383
TI  - Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by
      subunit shuffling of fungal polyketide synthases.
AB  - Combinatorial biosynthesis aspires to exploit the promiscuity of microbial
      anabolic pathways to engineer the synthesis of new chemical entities. Fungal
      benzenediol lactone (BDL) polyketides are important pharmacophores with wide
      ranging bioactivities, including heat shock response and immune system modulatory
      effects. Their biosynthesis on a pair of sequentially acting iterative polyketide
      synthases (iPKSs) offers a test case for the modularization of secondary
      metabolic pathways into "build-couple-pair" combinatorial synthetic schemes.
      Expression of random pairs of iPKS subunits from four BDL model systems in a
      yeast heterologous host created a diverse library of BDL congeners, including a
      polyketide with an unnatural skeleton and heat shock response-inducing activity.
      Pairwise heterocombinations of the iPKS subunits also helped to illuminate the
      innate, idiosyncratic programming of these enzymes. Even in combinatorial
      contexts, these biosynthetic programs remained largely unchanged, so that the
      iPKSs built their cognate biosynthons, coupled these building blocks into
      chimeric polyketide intermediates, and catalyzed intramolecular pairing to
      release macrocycles or alpha-pyrones. However, some heterocombinations also
      provoked stuttering, i.e., the relaxation of iPKSs chain length control to
      assemble larger homologous products. The success of such a plug and play approach
      to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural
      polyketides for drug discovery. 

PMID- 25049384
TI  - Complete genome of a nonphotosynthetic cyanobacterium in a diatom reveals recent
      adaptations to an intracellular lifestyle.
AB  - The evolution of mitochondria and plastids from bacterial endosymbionts were key
      events in the origin and diversification of eukaryotic cells. Although the
      ancient nature of these organelles makes it difficult to understand the earliest
      events that led to their establishment, the study of eukaryotic cells with
      recently evolved obligate endosymbiotic bacteria has the potential to provide
      important insight into the transformation of endosymbionts into organelles.
      Diatoms belonging to the family Rhopalodiaceae and their endosymbionts of
      cyanobacterial origin (i.e., "spheroid bodies") are emerging as a useful model
      system in this regard. The spheroid bodies, which appear to enable rhopalodiacean
      diatoms to use gaseous nitrogen, became established after the divergence of
      extant diatom families. Here we report what is, to our knowledge, the first
      complete genome sequence of a spheroid body, that of the rhopalodiacean diatom
      Epithemia turgida. The E. turgida spheroid body (EtSB) genome was found to
      possess a gene set for nitrogen fixation, as anticipated, but is reduced in size
      and gene repertoire compared with the genomes of their closest known free-living
      relatives. The presence of numerous pseudogenes in the EtSB genome suggests that
      genome reduction is ongoing. Most strikingly, our genomic data convincingly show
      that the EtSB has lost photosynthetic ability and is metabolically dependent on
      its host cell, unprecedented characteristics among cyanobacteria, and
      cyanobacterial symbionts. The diatom-spheroid body endosymbiosis is thus a unique
      system for investigating the processes underlying the integration of a bacterial
      endosymbiont into eukaryotic cells. 

PMID- 25049385
TI  - Impact of DNA3'pp5'G capping on repair reactions at DNA 3' ends.
AB  - Many biological scenarios generate "dirty" DNA 3'-PO4 ends that cannot be sealed
      by classic DNA ligases or extended by DNA polymerases. The noncanonical ligase
      RtcB can "cap" these ends via a unique chemical mechanism entailing transfer of
      GMP from a covalent RtcB-GMP intermediate to a DNA 3'-PO4 to form DNA3'pp5'G.
      Here, we show that capping protects DNA 3' ends from resection by Escherichia
      coli exonucleases I and III and from end-healing by T4 polynucleotide 3'
      phosphatase. By contrast, the cap is an effective primer for DNA synthesis. E.
      coli DNA polymerase I and Mycobacterium DinB1 extend the DNAppG primer to form an
      alkali-labile DNApp(rG)pDNA product. The addition of dNTP depends on pairing of
      the cap guanine with an opposing cytosine in the template strand. Aprataxin, an
      enzyme implicated in repair of A5'pp5'DNA ends formed during abortive ligation by
      classic ligases, is highly effective as a DNA 3' decapping enzyme, converting
      DNAppG to DNA3'p and GMP. We conclude that the biochemical impact of DNA capping
      is to prevent resection and healing of a 3'-PO4 end, while permitting DNA
      synthesis, at the price of embedding a ribonucleotide and a pyrophosphate linkage
      in the repaired strand. Aprataxin affords a means to counter the impact of DNA
      capping. 

PMID- 25049386
TI  - Molecular genetic framework for protophloem formation.
AB  - The phloem performs essential systemic functions in tracheophytes, yet little is
      known about its molecular genetic specification. Here we show that application of
      the peptide ligand CLAVATA3/embryo surrounding region 45 (CLE45) specifically
      inhibits specification of protophloem in Arabidopsis roots by locking the sieve
      element precursor cell in its preceding developmental state. CLE45 treatment, as
      well as viable transgenic expression of a weak CLE45(G6T) variant, interferes not
      only with commitment to sieve element fate but also with the formative sieve
      element precursor cell division that creates protophloem and metaphloem cell
      files. However, the absence of this division appears to be a secondary effect of
      discontinuous sieve element files and subsequent systemically reduced auxin
      signaling in the root meristem. In the absence of the formative sieve element
      precursor cell division, metaphloem identity is seemingly adopted by the normally
      procambial cell file instead, pointing to possibly independent positional cues
      for metaphloem formation. The protophloem formation and differentiation defects
      in brevis radix (brx) and octopus (ops) mutants are similar to those observed in
      transgenic seedlings with increased CLE45 activity and can be rescued by loss of
      function of a putative CLE45 receptor, barely any meristem 3 (BAM3). Conversely,
      a dominant gain-of-function ops allele or mild OPS dosage increase suppresses brx
      defects and confers CLE45 resistance. Thus, our data suggest that delicate
      quantitative interplay between the opposing activities of BAM3-mediated CLE45
      signals and OPS-dependent signals determines cellular commitment to protophloem
      sieve element fate, with OPS acting as a positive, quantitative master regulator
      of phloem fate.

PMID- 25049387
TI  - Prolactin prevents hepatocellular carcinoma by restricting innate immune
      activation of c-Myc in mice.
AB  - Women are more resistant to hepatocellular carcinoma (HCC) than men despite equal
      exposure to major risk factors, such as hepatitis B or C virus infection. Female
      resistance is hormone-dependent, as evidenced by the sharp increase in HCC
      incidence in postmenopausal women who do not take hormone replacement therapy. In
      rodent models sex-dimorphic HCC phenotypes are pituitary-dependent, suggesting
      that sex hormones act via the gonadal-hypophyseal axis. We found that the
      estrogen-responsive pituitary hormone prolactin (PRL), signaling through
      hepatocyte-predominant short-form prolactin receptors (PRLR-S), constrained TNF
      receptor-associated factor (TRAF)-dependent innate immune responses invoked by IL
      1beta, TNF-alpha, and LPS/Toll-like receptor 4 (TLR4), but not TRIF-dependent
      poly(I:C)/TLR3. PRL ubiquitinated and accelerated poststimulatory decay of a
      "trafasome" comprised of IRAK1, TRAF6, and MAP3K proteins, abrogating downstream
      activation of c-Myc-interacting pathways, including PI3K/AKT, mTORC1, p38 MAPK,
      and NF-kappaB. Consistent with this finding, we documented exaggerated male liver
      responses to immune stimuli in mice and humans. Tumor promotion through, but
      regulation above, the level of c-Myc was demonstrated by sex-independent HCC
      eruption in Alb-Myc transgenic mice. PRL deficiency accelerated liver
      carcinogenesis in Prl(-/-) mice of both sexes. Conversely, pharmacologic PRL
      mobilization using the dopamine D2 receptor antagonist domperidone prevented HCC
      in tumor-prone C3H/HeN males. Viewed together, our results demonstrate that PRL
      constrains tumor-promoting liver inflammation by inhibiting MAP3K-dependent
      activation of c-Myc at the level of the trafasome. PRL-targeted therapy may hold
      promise for reducing the burden of liver cancer in high-risk men and women. 

PMID- 25049388
TI  - Denervation protects limbs from inflammatory arthritis via an impact on the
      microvasculature.
AB  - Two-way communication between the mammalian nervous and immune systems is
      increasingly recognized and appreciated. An intriguing example of such crosstalk
      comes from clinical observations dating from the 1930s: Patients who suffer a
      stroke and then develop rheumatoid arthritis atypically present with arthritis on
      only one side, the one not afflicted with paralysis. Here we successfully modeled
      hemiplegia-induced protection from arthritis using the K/BxN serum-transfer
      system, focused on the effector phase of inflammatory arthritis. Experiments
      entailing pharmacological inhibitors, genetically deficient mouse strains, and
      global transcriptome analyses failed to associate the protective effect with a
      single nerve quality (i.e., with the sympathetic, parasympathetic, or sensory
      nerves). Instead, there was clear evidence that denervation had a long-term
      effect on the limb microvasculature: The rapid and joint-localized vascular leak
      that typically accompanies and promotes serum-transferred arthritis was
      compromised in denervated limbs. This defect was reflected in the transcriptome
      of endothelial cells, the expression of several genes impacting vascular leakage
      or transendothelial cell transmigration being altered in denervated limbs. These
      findings highlight a previously unappreciated pathway to dissect and eventually
      target in inflammatory arthritis. 

PMID- 25049389
TI  - Side-chain conformation at the selectivity filter shapes the permeation free
      energy landscape of an ion channel.
AB  - On the basis of single-channel currents recorded from the muscle nicotinic
      acetylcholine receptor (AChR), we have recently hypothesized that the
      conformation adopted by the glutamate side chains at the first turn of the pore
      lining alpha-helices is a key determinant of the rate of ion permeation. In this
      paper, we set out to test these ideas within a framework of atomic detail and
      stereochemical rigor by conducting all-atom molecular dynamics and Brownian
      dynamics simulations on an extensively validated model of the open-channel muscle
      AChR. Our simulations provided ample support to the notion that the different
      rotamers of these glutamates partition into two classes that differ markedly in
      their ability to catalyze ion conduction, and that the conformations of the four
      wild-type glutamates are such that two of them "fall" in each rotamer class.
      Moreover, the simulations allowed us to identify the mm (chi(1) ? -60 degrees ;
      chi(2) ? -60 degrees ) and tp (chi(1) ? 180 degrees ; chi(2) ? +60 degrees )
      rotamers as the likely conduction-catalyzing conformations of the AChR's
      selectivity-filter glutamates. More generally, our work shows an example of how
      experimental benchmarks can guide molecular simulations into providing a type of
      structural and mechanistic insight that seems otherwise unattainable.

PMID- 25049390
TI  - Next-generation sequencing identifies rare variants associated with Noonan
      syndrome.
AB  - Noonan syndrome (NS) is a relatively common genetic disorder, characterized by
      typical facies, short stature, developmental delay, and cardiac abnormalities.
      Known causative genes account for 70-80% of clinically diagnosed NS patients, but
      the genetic basis for the remaining 20-30% of cases is unknown. We performed next
      generation sequencing on germ-line DNA from 27 NS patients lacking a mutation in
      the known NS genes. We identified gain-of-function alleles in Ras-like without
      CAAX 1 (RIT1) and mitogen-activated protein kinase kinase 1 (MAP2K1) and
      previously unseen loss-of-function variants in RAS p21 protein activator 2
      (RASA2) that are likely to cause NS in these patients. Expression of the mutant
      RASA2, MAP2K1, or RIT1 alleles in heterologous cells increased RAS-ERK pathway
      activation, supporting a causative role in NS pathogenesis. Two patients had more
      than one disease-associated variant. Moreover, the diagnosis of an individual
      initially thought to have NS was revised to neurofibromatosis type 1 based on an
      NF1 nonsense mutation detected in this patient. Another patient harbored a
      missense mutation in NF1 that resulted in decreased protein stability and
      impaired ability to suppress RAS-ERK activation; however, this patient continues
      to exhibit a NS-like phenotype. In addition, a nonsense mutation in RPS6KA3 was
      found in one patient initially diagnosed with NS whose diagnosis was later
      revised to Coffin-Lowry syndrome. Finally, we identified other potential
      candidates for new NS genes, as well as potential carrier alleles for unrelated
      syndromes. Taken together, our data suggest that next-generation sequencing can
      provide a useful adjunct to RASopathy diagnosis and emphasize that the standard
      clinical categories for RASopathies might not be adequate to describe all
      patients. 

PMID- 25049391
TI  - Method for identifying phosphorylated substrates of specific cyclin/cyclin
      dependent kinase complexes.
AB  - In eukaryotes, cell cycle progression is controlled by cyclin/cyclin-dependent
      kinase (CDK) pairs. To better understand the details of this process, it is
      necessary to dissect the CDK's substrate pool in a cyclin- and cell cycle stage
      specific way. Here, we report a mass spectrometry-based method that couples rapid
      isolation of native kinase-substrate complexes to on-bead phosphorylation with
      heavy-labeled ATP (ATP-gamma-(18)O4). This combined in vivo/in vitro method was
      developed for identifying cyclin/CDK substrates together with their sites of
      phosphorylation. We used the method to identify Clb5 (S-cyclin)/Cdc28 and Cln2
      (G1/S-cyclin)/Cdc28 substrates during S phase in Saccharomyces cerevisiae (Cdc28
      is the master CDK in budding yeast). During the work, we discovered that
      Clb5/Cdc28 specifically phosphorylates S429 in the disordered tail of Cdc14, an
      essential phosphatase antagonist of Cdc28. This phosphorylation severely
      decreases the activity of Cdc14, providing a means for modulating the balance of
      CDK and phosphatase activity. 

PMID- 25049392
TI  - Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription
      factor.
AB  - Members of the calmodulin-binding transcription activator (CAMTA) family of
      proteins function as calcium-sensitive regulators of gene expression in
      multicellular organisms ranging from plants to humans. Here, we show that global
      or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje
      cell degeneration and cerebellar atrophy, partially resembling the consequences
      of haploinsufficiency of the human CAMTA1 locus. Gene-expression analysis
      identified a large collection of neuronal genes that were dysregulated in the
      brains of CAMTA1-mutant mice, and elucidation of a consensus sequence for binding
      of CAMTA proteins to DNA revealed the association of CAMTA-binding sites with
      many of these genes. We conclude that CAMTA1 plays an essential role in the
      control of Purkinje cell function and survival. CAMTA1-mutant mice provide a
      model to study the molecular mechanisms of neurodegenerative diseases and for
      screening potential therapeutic interventions for such disorders. 

PMID- 25049393
TI  - Regulatory effects of SKAR in interferon alpha signaling and its role in the
      generation of type I IFN responses.
AB  - We provide evidence that S6 kinase 1 (S6K1) Aly/REF-like target (SKAR) is engaged
      in IFN-alpha signaling and plays a key role in the generation of IFN responses.
      Our data demonstrate that IFN-alpha induces phosphorylation of SKAR, which is
      mediated by either the p90 ribosomal protein S6 kinase (RSK) or p70 S6 kinase
      (S6K1), in a cell type-specific manner. This type I IFN-inducible phosphorylation
      of SKAR results in enhanced interaction with the eukaryotic initiation factor
      (eIF)4G and recruitment of activated RSK1 to 5' cap mRNA. Our studies also
      establish that SKAR is present in cap-binding CBP80 immune complexes and that
      this interaction is mediated by eIF4G. We demonstrate that inducible protein
      expression of key IFN-alpha-regulated protein products such as ISG15 and
      p21(WAF1/CIP1) requires SKAR activity. Importantly, our studies define a
      requirement for SKAR in the generation of IFN-alpha-dependent inhibitory effects
      on malignant hematopoietic progenitors from patients with chronic myeloid
      leukemia or myeloproliferative neoplasms. Taken altogether, these findings
      establish critical and essential roles for SKAR in the regulation of mRNA
      translation of IFN-sensitive genes and induction of IFN-alpha biological
      responses. 

PMID- 25049394
TI  - Critical role of canonical transient receptor potential channel 7 in initiation
      of seizures.
AB  - Status epilepticus (SE) is a life-threatening disease that has been recognized
      since antiquity but still causes over 50,000 deaths annually in the United
      States. The prevailing view on the pathophysiology of SE is that it is sustained
      by a loss of normal inhibitory mechanisms of neuronal activity. However, the
      early process leading to the initiation of SE is not well understood. Here, we
      show that, as seen in electroencephalograms, SE induced by the muscarinic agonist
      pilocarpine in mice is preceded by a specific increase in the gamma wave, and
      genetic ablation of canonical transient receptor potential channel (TRPC) 7
      significantly reduces this pilocarpine-induced increase of gamma wave activity,
      preventing the occurrence of SE. At the cellular level, TRPC7 plays a critical
      role in the generation of spontaneous epileptiform burst firing in cornu ammonis
      (CA) 3 pyramidal neurons in brain slices. At the synaptic level, TRPC7 plays a
      significant role in the long-term potentiation at the CA3 recurrent collateral
      synapses and Schaffer collateral-CA1 synapses, but not at the mossy fiber-CA3
      synapses. Taken together, our data suggest that epileptiform burst firing
      generated in the CA3 region by activity-dependent enhancement of recurrent
      collateral synapses may be an early event in the initiation process of SE and
      that TRPC7 plays a critical role in this cellular event. Our findings reveal that
      TRPC7 is intimately involved in the initiation of seizures both in vitro and in
      vivo. To our knowledge, this contribution to initiation of seizures is the first
      identified functional role for the TRPC7 ion channel. 

PMID- 25049395
TI  - Coordinated photomorphogenic UV-B signaling network captured by mathematical
      modeling.
AB  - Long-wavelength and low-fluence UV-B light is an informational signal known to
      induce photomorphogenic development in plants. Using the model plant Arabidopsis
      thaliana, a variety of factors involved in UV-B-specific signaling have been
      experimentally characterized over the past decade, including the UV-B light
      receptor UV resistance locus 8; the positive regulators constitutive
      photomorphogenesis 1 and elongated hypocotyl 5; and the negative regulators
      cullin4, repressor of UV-B photomorphogenesis 1 (RUP1), and RUP2. Individual
      genetic and molecular studies have revealed that these proteins function in
      either positive or negative regulatory capacities for the sufficient and balanced
      transduction of photomorphogenic UV-B signal. Less is known, however, regarding
      how these signaling events are systematically linked. In our study, we use a
      systems biology approach to investigate the dynamic behaviors and correlations of
      multiple signaling components involved in Arabidopsis UV-B-induced
      photomorphogenesis. We define a mathematical representation of photomorphogenic
      UV-B signaling at a temporal scale. Supplemented with experimental validation,
      our computational modeling demonstrates the functional interaction that occurs
      among different protein complexes in early and prolonged response to
      photomorphogenic UV-B. 

PMID- 25049396
TI  - Residue level quantification of protein stability in living cells.
AB  - The intracellular milieu differs from the dilute conditions in which most
      biophysical and biochemical studies are performed. This difference has led both
      experimentalists and theoreticians to tackle the challenging task of
      understanding how the intracellular environment affects the properties of
      biopolymers. Despite a growing number of in-cell studies, there is a lack of
      quantitative, residue-level information about equilibrium thermodynamic protein
      stability under nonperturbing conditions. We report the use of NMR-detected
      hydrogen-deuterium exchange of quenched cell lysates to measure individual
      opening free energies of the 56-aa B1 domain of protein G (GB1) in living
      Escherichia coli cells without adding destabilizing cosolutes or heat.
      Comparisons to dilute solution data (pH 7.6 and 37  degrees C) show that opening
      free energies increase by as much as 1.14 +/- 0.05 kcal/mol in cells.
      Importantly, we also show that homogeneous protein crowders destabilize GB1,
      highlighting the challenge of recreating the cellular interior. We discuss our
      findings in terms of hard-core excluded volume effects, charge-charge GB1-crowder
      interactions, and other factors. The quenched lysate method identifies the
      residues most important for folding GB1 in cells, and should prove useful for
      quantifying the stability of other globular proteins in cells to gain a more
      complete understanding of the effects of the intracellular environment on protein
      chemistry. 

PMID- 25049397
TI  - Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion
      kinase by inducing clustering and conformational changes.
AB  - Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key
      roles in integrating growth and cell matrix adhesion signals, and FAK is a major
      driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors
      is well known to trigger FAK signaling, and many of the players involved are
      known; however, mechanistically, FAK activation is not understood. Here, using a
      multidisciplinary approach, including biochemical, biophysical, structural,
      computational, and cell biology approaches, we provide a detailed view of a
      multistep activation mechanism of FAK initiated by phosphatidylinositol-4,5
      bisphosphate [PI(4,5)P2]. Interestingly, the mechanism differs from canonical
      NRTK activation and is tailored to the dual catalytic and scaffolding function of
      FAK. We find PI(4,5)P2 induces clustering of FAK on the lipid bilayer by binding
      a basic region in the regulatory 4.1, ezrin, radixin, moesin homology (FERM)
      domain. In these clusters, PI(4,5)P2 induces a partially open FAK conformation
      where the autophosphorylation site is exposed, facilitating efficient
      autophosphorylation and subsequent Src recruitment. However, PI(4,5)P2 does not
      release autoinhibitory interactions; rather, Src phosphorylation of the
      activation loop in FAK results in release of the FERM/kinase tether and full
      catalytic activation. We propose that PI(4,5)P2 and its generation in focal
      adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Igamma are
      important in linking integrin signaling to FAK activation. 

PMID- 25049398
TI  - Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor.
AB  - The retinoblastoma tumor suppressor protein pRb is a key regulator of cell cycle
      progression and mediator of the DNA damage response. Lysine methylation at K810,
      which occurs within a critical Cdk phosphorylation motif, holds pRb in the
      hypophosphorylated growth-suppressing state. We show here that methyl K810 is
      read by the tandem tudor domain containing tumor protein p53 binding protein 1
      (53BP1). Structural elucidation of 53BP1 in complex with a methylated K810 pRb
      peptide emphasized the role of the 53BP1 tandem tudor domain in recognition of
      the methylated lysine and surrounding residues. Significantly, binding of 53BP1
      to methyl K810 occurs on E2 promoter binding factor target genes and allows pRb
      activity to be effectively integrated with the DNA damage response. Our results
      widen the repertoire of cellular targets for 53BP1 and suggest a previously
      unidentified role for 53BP1 in regulating pRb tumor suppressor activity. 

PMID- 25049399
TI  - Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR
      virulence regulator.
AB  - Although the bovine tuberculosis (TB) agent, Mycobacterium bovis, may infect
      humans and cause disease, long-term epidemiological data indicate that humans
      represent a spill-over host in which infection with M. bovis is not self
      maintaining. Indeed, human-to-human transmission of M. bovis strains and other
      members of the animal lineage of the tubercle bacilli is very rare. Here, we
      report on three mutations affecting the two-component virulence regulation system
      PhoP/PhoR (PhoPR) in M. bovis and in the closely linked Mycobacterium africanum
      lineage 6 (L6) that likely account for this discrepancy. Genetic transfer of
      these mutations into the human TB agent, Mycobacterium tuberculosis, resulted in
      down-regulation of the PhoP regulon, with loss of biologically active lipids,
      reduced secretion of the 6-kDa early antigenic target (ESAT-6), and lower
      virulence. Remarkably, the deleterious effects of the phoPR mutations were partly
      compensated by a deletion, specific to the animal-adapted and M. africanum L6
      lineages, that restores ESAT-6 secretion by a PhoPR-independent mechanism.
      Similarly, we also observed that insertion of an IS6110 element upstream of the
      phoPR locus may completely revert the phoPR-bovis-associated fitness loss, which
      is the case for an exceptional M. bovis human outbreak strain from Spain. Our
      findings ultimately explain the long-term epidemiological data, suggesting that
      M. bovis and related phoPR-mutated strains pose a lower risk for progression to
      overt human TB, with major impact on the evolutionary history of TB. 

PMID- 25049400
TI  - Synthesis of bioactive protein hydrogels by genetically encoded SpyTag-SpyCatcher
      chemistry.
AB  - Protein-based hydrogels have emerged as promising alternatives to synthetic
      hydrogels for biomedical applications, owing to the precise control of structure
      and function enabled by protein engineering. Nevertheless, strategies for
      assembling 3D molecular networks that carry the biological information encoded in
      full-length proteins remain underdeveloped. Here we present a robust protein
      gelation strategy based on a pair of genetically encoded reactive partners,
      SpyTag and SpyCatcher, that spontaneously form covalent isopeptide linkages under
      physiological conditions. The resulting "network of Spies" may be designed to
      include cell-adhesion ligands, matrix metalloproteinase-1 cleavage sites, and
      full-length globular proteins [mCherry and leukemia inhibitory factor (LIF)]. The
      LIF network was used to encapsulate mouse embryonic stem cells; the encapsulated
      cells remained pluripotent in the absence of added LIF. These results illustrate
      a versatile strategy for the creation of information-rich biomaterials. 

PMID- 25049401
TI  - Dissecting allosteric effects of activator-coactivator complexes using a covalent
      small molecule ligand.
AB  - Allosteric binding events play a critical role in the formation and stability of
      transcriptional activator-coactivator complexes, perhaps in part due to the often
      intrinsically disordered nature of one or more of the constituent partners. The
      kinase-inducible domain interacting (KIX) domain of the master coactivator CREB
      binding protein/p300 is a conformationally dynamic domain that complexes with
      transcriptional activators at two discrete binding sites in allosteric
      communication. The complexation of KIX with the transcriptional activation domain
      of mixed-lineage leukemia protein leads to an enhancement of binding by the
      activation domain of CREB (phosphorylated kinase-inducible domain of CREB) to the
      second site. A transient kinetic analysis of the ternary complex formation aided
      by small molecule ligands that induce positive or negative cooperative binding
      reveals that positive cooperativity is largely governed by stabilization of the
      bound complex as indicated by a decrease in koff. Thus, this suggests the
      increased binding affinity for the second ligand is not due to an allosteric
      creation of a more favorable binding interface by the first ligand. This is
      consistent with data from us and from others indicating that the on rates of
      conformationally dynamic proteins approach the limits of diffusion. In contrast,
      negative cooperativity is manifested by alterations in both kon and koff,
      suggesting stabilization of the binary complex. 

PMID- 25049402
TI  - Pathway of binding of the intrinsically disordered mitochondrial inhibitor
      protein to F1-ATPase.
AB  - The hydrolysis of ATP by the ATP synthase in mitochondria is inhibited by a
      protein called IF1. Bovine IF1 has 84 amino acids, and its N-terminal inhibitory
      region is intrinsically disordered. In a known structure of bovine F1-ATPase
      inhibited with residues 1-60 of IF1, the inhibitory region from residues 1-50 is
      mainly alpha-helical and buried deeply at the alpha(DP)beta(DP)-catalytic
      interface, where it forms extensive interactions with five of the nine subunits
      of F1-ATPase but mainly with the beta(DP)-subunit. As described here, on the
      basis of two structures of inhibited complexes formed in the presence of large
      molar excesses of residues 1-60 of IF1 and of a version of IF1 with the mutation
      K39A, it appears that the intrinsically disordered inhibitory region interacts
      first with the alphaEbetaE-catalytic interface, the most open of the three
      catalytic interfaces, where the available interactions with the enzyme allow it
      to form an alpha-helix from residues 31-49. Then, in response to the hydrolysis
      of an ATP molecule and the associated partial closure of the interface to the
      alphaTPbetaTP state, the extent of the folded alpha-helical region of IF1
      increases to residues 23-50 as more interactions with the enzyme become possible.
      Finally, in response to the hydrolysis of a second ATP molecule and a concomitant
      120 degrees  rotation of the gamma-subunit, the interface closes further to the
      alpha(DP)beta(DP)-state, allowing more interactions to form between the enzyme
      and IF1. The structure of IF1 now extends to its maximally folded state found in
      the previously observed inhibited complex.

PMID- 25049404
TI  - Modeling gating charge and voltage changes in response to charge separation in
      membrane proteins.
AB  - Measurements of voltage changes in response to charge separation within membrane
      proteins can offer fundamental information on mechanisms of charge transport and
      displacement processes. A recent example is provided by studies of cytochrome c
      oxidase. However, the interpretation of the observed voltage changes in terms of
      the number of charge equivalents and transfer distances is far from being trivial
      or unique. Using continuum approaches to describe the voltage generation may
      involve significant uncertainties and reliable microscopic simulations are not
      yet available. Here, we attempt to solve this problem by using a coarse-grained
      model of membrane proteins, which includes an explicit description of the
      membrane, the electrolytes, and the electrodes. The model evaluates the gating
      charges and the electrode potentials (c.f. measured voltage) upon charge transfer
      within the protein. The accuracy of the model is evaluated by a comparison of
      measured voltage changes associated with electron and proton transfer in
      bacterial photosynthetic reaction centers to those calculated using our coarse
      grained model. The calculations reproduce the experimental observations and thus
      indicate that the method is of general use. Interestingly, it is found that
      charge-separation processes with different spatial directions (but the same
      distance perpendicular to the membrane) can give similar observed voltage
      changes, which indicates that caution should be exercised when using simplified
      interpretation of the relationship between charge displacement and voltage
      changes. 

PMID- 25049403
TI  - A family-oriented psychosocial intervention reduces inflammation in low-SES
      African American youth.
AB  - Children of low socioeconomic status (SES) are at elevated risk for health
      problems across the lifespan. Observational studies suggest that nurturant
      parenting might offset some of these health risks, but their design precludes
      inferences about causal direction and clinical utility. Here we ask whether a
      psychosocial intervention, focused improving parenting, strengthening family
      relationships, and building youth competencies, can reduce inflammation in low
      SES, African Americans from the rural South. The trial involved 272 mothers and
      their 11-y-old children from rural Georgia, half of whose annual household
      incomes were below the federal poverty line. Families were randomly assigned to a
      7-wk psychosocial intervention or to a control condition. When youth reached age
      19, peripheral blood was collected to quantify six cytokines that orchestrate
      inflammation, the dysregulation of which contributes to many of the health
      problems known to pattern by SES. Youth who participated in the intervention had
      significantly less inflammation on all six indicators relative to controls (all P
      values < 0.001; effect sizes in Cohen's d units ranged from -0.69 to -0.91).
      Mediation analyses suggested that improved parenting was partially responsible
      for the intervention's benefits. Inflammation was lowest among youth who received
      more nurturant-involved parenting, and less harsh-inconsistent parenting, as a
      consequence of the intervention. These findings have theoretical implications for
      research on resilience to adversity and the early origins of disease. If
      substantiated, they may also highlight a strategy for practitioners and
      policymakers to use in ameliorating social and racial health disparities. 

PMID- 25049405
TI  - Oceanographic dynamics and the end of the last interglacial in the subpolar North
      Atlantic.
AB  - The last interglacial interval was terminated by the inception of a long,
      progressive glaciation that is attributed to astronomically influenced changes in
      the seasonal distribution of sunlight over the earth. However, the feedbacks,
      internal dynamics, and global teleconnections associated with declining northern
      summer insolation remain incompletely understood. Here we show that a crucial
      early step in glacial inception involves the weakening of the subpolar gyre (SPG)
      circulation of the North Atlantic Ocean. Detailed new records of microfossil
      foraminifera abundance and stable isotope ratios in deep sea sediments from Ocean
      Drilling Program site 984 south of Iceland reveal repeated, progressive cold
      water-mass expansions into subpolar latitudes during the last peak interglacial
      interval, marine isotope substage 5e. These movements are expressed as a sequence
      of progressively extensive southward advances and subsequent retreats of a
      hydrographic boundary that may have been analogous to the modern Arctic front,
      and associated with rapid changes in the strength of the SPG. This persistent
      millennial-scale oceanographic oscillation accompanied a long-term cooling trend
      at a time of slowly declining northern summer insolation, providing an early link
      in the propagation of those insolation changes globally, and resulting in a rapid
      transition from extensive regional warmth to the dramatic instability of the
      subsequent ~ 100 ka.

PMID- 25049406
TI  - Exploring exoplanet populations with NASA's Kepler Mission.
AB  - The Kepler Mission is exploring the diversity of planets and planetary systems.
      Its legacy will be a catalog of discoveries sufficient for computing planet
      occurrence rates as a function of size, orbital period, star type, and insolation
      flux. The mission has made significant progress toward achieving that goal. Over
      3,500 transiting exoplanets have been identified from the analysis of the first 3
      y of data, 100 planets of which are in the habitable zone. The catalog has a high
      reliability rate (85-90% averaged over the period/radius plane), which is
      improving as follow-up observations continue. Dynamical (e.g., velocimetry and
      transit timing) and statistical methods have confirmed and characterized hundreds
      of planets over a large range of sizes and compositions for both single- and
      multiple-star systems. Population studies suggest that planets abound in our
      galaxy and that small planets are particularly frequent. Here, I report on the
      progress Kepler has made measuring the prevalence of exoplanets orbiting within
      one astronomical unit of their host stars in support of the National Aeronautics
      and Space Administration's long-term goal of finding habitable environments
      beyond the solar system. 

PMID- 25049407
TI  - Energy conservation by oxidation of formate to carbon dioxide and hydrogen via a
      sodium ion current in a hyperthermophilic archaeon.
AB  - Thermococcus onnurineus NA1 is known to grow by the anaerobic oxidation of
      formate to CO2 and H2, a reaction that operates near thermodynamic equilibrium.
      Here we demonstrate that this reaction is coupled to ATP synthesis by a
      transmembrane ion current. Formate oxidation leads to H(+) translocation across
      the cytoplasmic membrane that then drives Na(+) translocation. The ion
      translocating electron transfer system is rather simple, consisting of only a
      formate dehydrogenase module, a membrane-bound hydrogenase module, and a
      multisubunit Na(+)/H(+) antiporter module. The electrochemical Na(+) gradient
      established then drives ATP synthesis. These data give a mechanistic explanation
      for chemiosmotic energy conservation coupled to formate oxidation to CO2 and H2.
      Because it is discussed that the membrane-bound hydrogenase with the Na(+)/H(+)
      antiporter module are ancestors of complex I of mitochondrial and bacterial
      electron transport these data also shed light on the evolution of ion transport
      in complex I-like electron transport chains. 

PMID- 25049408
TI  - Control of axon-axon attraction by Semaphorin reverse signaling.
AB  - Semaphorin family proteins are well-known axon guidance ligands. Recent studies
      indicate that certain transmembrane Semaphorins can also function as guidance
      receptors to mediate axon-axon attraction or repulsion. The mechanisms by which
      Semaphorin reverse signaling modulates axon-surface affinity, however, remain
      unknown. In this study, we reveal a novel mechanism underlying upregulation of
      axon-axon attraction by Semaphorin-1a (Sema1a) reverse signaling in the
      developing Drosophila visual system. Sema1a promotes the phosphorylation and
      activation of Moesin (Moe), a member of the ezrin/radixin/moesin family of
      proteins, and downregulates the level of active Rho1 in photoreceptor axons. We
      propose that Sema1a reverse signaling activates Moe, which in turn upregulates
      Fas2-mediated axon-axon attraction by inhibiting Rho1. 

PMID- 25049409
TI  - A phage protein that inhibits the bacterial ATPase required for type IV pilus
      assembly.
AB  - Type IV pili (TFPs) are required for bacterial twitching motility and for phage
      infection in the opportunistic human pathogen Pseudomonas aeruginosa. Here we
      describe a phage-encoded protein, D3112 protein gp05 (hereafter referred to as
      Tip, representing twitching inhibitory protein), whose expression is necessary
      and sufficient to mediate the inhibition of twitching motility. Tip interacts
      with and blocks the activity of bacterial-encoded PilB, the TFP
      assembly/extension ATPase, at an internal 40-aa region unique to PilB. Tip
      expression results in the loss of surface piliation. Based on these observations
      and the fact that many P. aeruginosa phages require TFPs for infection, Tip
      mediated twitching inhibition may represent a generalized strategy for
      superinfection exclusion. Moreover, because TFPs are required for full virulence,
      PilB may be an attractive target for the development of novel antiinfectives. 

PMID- 25049410
TI  - RNA-directed gene editing specifically eradicates latent and prevents new HIV-1
      infection.
AB  - AIDS remains incurable due to the permanent integration of HIV-1 into the host
      genome, imparting risk of viral reactivation even after antiretroviral therapy.
      New strategies are needed to ablate the viral genome from latently infected
      cells, because current methods are too inefficient and prone to adverse off
      target effects. To eliminate the integrated HIV-1 genome, we used the Cas9/guide
      RNA (gRNA) system, in single and multiplex configurations. We identified highly
      specific targets within the HIV-1 LTR U3 region that were efficiently edited by
      Cas9/gRNA, inactivating viral gene expression and replication in latently
      infected microglial, promonocytic, and T cells. Cas9/gRNAs caused neither
      genotoxicity nor off-target editing to the host cells, and completely excised a
      9,709-bp fragment of integrated proviral DNA that spanned from its 5' to 3' LTRs.
      Furthermore, the presence of multiplex gRNAs within Cas9-expressing cells
      prevented HIV-1 infection. Our results suggest that Cas9/gRNA can be engineered
      to provide a specific, efficacious prophylactic and therapeutic approach against
      AIDS. 

PMID- 25049411
TI  - An obligately aerobic soil bacterium activates fermentative hydrogen production
      to survive reductive stress during hypoxia.
AB  - Oxygen availability is a major factor and evolutionary force determining the
      metabolic strategy of bacteria colonizing an environmental niche. In the soil,
      conditions can switch rapidly between oxia and anoxia, forcing soil bacteria to
      remodel their energy metabolism accordingly. Mycobacterium is a dominant genus in
      the soil, and all its species are obligate aerobes. Here we show that an obligate
      aerobe, the soil actinomycete Mycobacterium smegmatis, adopts an anaerobe-type
      strategy by activating fermentative hydrogen production to adapt to hypoxia. This
      process is controlled by the two-component system DosR-DosS/DosT, an oxygen and
      redox sensor that is well conserved in mycobacteria. We show that DosR tightly
      regulates the two [NiFe]-hydrogenases: Hyd3 (MSMEG_3931-3928) and Hyd2
      (MSMEG_2719-2718). Using genetic manipulation and high-sensitivity GC, we
      demonstrate that Hyd3 facilitates the evolution of H2 when oxygen is depleted.
      Combined activity of Hyd2 and Hyd3 was necessary to maintain an optimal
      NAD(+)/NADH ratio and enhanced adaptation to and survival of hypoxia. We
      demonstrate that fermentatively-produced hydrogen can be recycled when fumarate
      or oxygen become available, suggesting Mycobacterium smegmatis can switch between
      fermentation, anaerobic respiration, and aerobic respiration. Hydrogen metabolism
      enables this obligate aerobe to rapidly meet its energetic needs when switching
      between microoxic and anoxic conditions and provides a competitive advantage in
      low oxygen environments. 

PMID- 25049412
TI  - Subpolar addition of new cell wall is directed by DivIVA in mycobacteria.
AB  - Mycobacteria are surrounded by a complex multilayered envelope and elongate at
      the poles. The principles that organize the coordinated addition of chemically
      diverse cell wall layers during polar extension remain unclear. We show that
      enzymes mediating the terminal cytosolic steps of peptidoglycan, arabinogalactan,
      and mycolic acid synthesis colocalize at sites of cell growth or division. The
      tropomyosin-like protein, DivIVA, is targeted to the negative curvature of the
      pole, is enriched at the growing end, and determines cell shape from this site.
      In contrast, cell wall synthetic complexes are concentrated at a distinct
      subpolar location. When viewed at subdiffraction resolution, new peptidoglycan is
      deposited at this subpolar site, and inert cell wall covers the DivIVA-marked
      tip. The differentiation between polar tip and cell wall synthetic complexes is
      also apparent at the biochemical level. Enzymes that generate mycolate precursors
      interact with DivIVA, but the final condensation of mycolic acids occurs in a
      distinct protein complex at the site of nascent cell wall addition. We propose an
      ultrastructural model of mycobacterial polar growth where new cell wall is added
      in an annular zone below the cell tip. This model may be broadly applicable to
      other bacterial and fungal organisms that grow via polar extension. 

PMID- 25049414
TI  - Secondary bacterial flagellar system improves bacterial spreading by increasing
      the directional persistence of swimming.
AB  - As numerous bacterial species, Shewanella putrefaciens CN-32 possesses a complete
      secondary flagellar system. A significant subpopulation of CN-32 cells induces
      expression of the secondary system under planktonic conditions, resulting in
      formation of one, sometimes two, filaments at lateral positions in addition to
      the primary polar flagellum. Mutant analysis revealed that the single chemotaxis
      system primarily or even exclusively addresses the main polar flagellar system.
      Cells with secondary filaments outperformed their monopolarly flagellated
      counterparts in spreading on soft-agar plates and through medium-filled channels
      despite having lower swimming speed. While mutant cells with only polar flagella
      navigate by a "run-reverse-flick" mechanism resulting in effective cell
      realignments of about 90 degrees , wild-type cells with secondary filaments
      exhibited a range of realignment angles with an average value of smaller than 90
      degrees . Mathematical modeling and computer simulations demonstrated that the
      smaller realignment angle of wild-type cells results in the higher directional
      persistence, increasing spreading efficiency both with and without a chemical
      gradient. Taken together, we propose that in S. putrefaciens CN-32, cell
      propulsion and directional switches are mainly mediated by the polar flagellar
      system, while the secondary filament increases the directional persistence of
      swimming and thus of spreading in the environment. 

PMID- 25049413
TI  - Structure of the eukaryotic translation initiation factor eIF4E in complex with
      4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.
AB  - The interaction of the eukaryotic translation initiation factor eIF4E with the
      initiation factor eIF4G recruits the 40S ribosomal particle to the 5' end of
      mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic
      translation of nearly all genes. Efficient recruitment of the 40S particle is
      particularly important for translation of mRNAs encoding oncoproteins and growth
      promoting factors, which often harbor complex 5' UTRs and require efficient
      initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a
      previously unpursued route for developing anticancer agents. Indeed, we
      discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that
      inhibit translation initiation both in vitro and in vivo and were used
      successfully in numerous cancer-biology and neurobiology studies. However, their
      detailed molecular mechanism of action has remained elusive. Here, we show that
      the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on
      eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high
      resolution crystal structures are congruent with this mechanism, where 4EGI-1
      attaches to a hydrophobic pocket of eIF4E between beta-sheet2 (L60-T68) and alpha
      helix1 (E69-N77), causing localized conformational changes mainly in the H78-L85
      region. It acts by unfolding a short 310-helix (S82-L85) while extending alpha
      helix1 by one turn (H78-S82). This unusual helix rearrangement has not been seen
      in any previous eIF4E structure and reveals elements of an allosteric inhibition
      mechanism leading to the dislocation of eIF4G from eIF4E. 

PMID- 25049415
TI  - Temporal control over the initiation of cell motility by a regulator of G-protein
      signaling.
AB  - The control over the acquisition of cell motility is central for a variety of
      biological processes in development, homeostasis, and disease. An attractive in
      vivo model for investigating the regulation of migration initiation is that of
      primordial germ cells (PGCs) in zebrafish embryos. In this study, we show that,
      following PGC specification, the cells can polarize but do not migrate before the
      time chemokine-encoded directional cues are established. We found that the
      regulator of G-protein signaling 14a protein, whose RNA is a newly identified
      germ plasm component, regulates the temporal relations between the appearance of
      the guidance molecules and the acquisition of cellular motility by regulating E
      cadherin levels. 

PMID- 25049416
TI  - Land, irrigation water, greenhouse gas, and reactive nitrogen burdens of meat,
      eggs, and dairy production in the United States.
AB  - Livestock production impacts air and water quality, ocean health, and greenhouse
      gas (GHG) emissions on regional to global scales and it is the largest use of
      land globally. Quantifying the environmental impacts of the various livestock
      categories, mostly arising from feed production, is thus a grand challenge of
      sustainability science. Here, we quantify land, irrigation water, and reactive
      nitrogen (Nr) impacts due to feed production, and recast published full life
      cycle GHG emission estimates, for each of the major animal-based categories in
      the US diet. Our calculations reveal that the environmental costs per consumed
      calorie of dairy, poultry, pork, and eggs are mutually comparable (to within a
      factor of 2), but strikingly lower than the impacts of beef. Beef production
      requires 28, 11, 5, and 6 times more land, irrigation water, GHG, and Nr,
      respectively, than the average of the other livestock categories. Preliminary
      analysis of three staple plant foods shows two- to sixfold lower land, GHG, and
      Nr requirements than those of the nonbeef animal-derived calories, whereas
      irrigation requirements are comparable. Our analysis is based on the best data
      currently available, but follow-up studies are necessary to improve parameter
      estimates and fill remaining knowledge gaps. Data imperfections notwithstanding,
      the key conclusion--that beef production demands about 1 order of magnitude more
      resources than alternative livestock categories--is robust under existing
      uncertainties. The study thus elucidates the multiple environmental benefits of
      potential, easy-to-implement dietary changes, and highlights the uniquely high
      resource demands of beef.

PMID- 25049417
TI  - PAPD5-mediated 3' adenylation and subsequent degradation of miR-21 is disrupted
      in proliferative disease.
AB  - Next-generation sequencing experiments have shown that microRNAs (miRNAs) are
      expressed in many different isoforms (isomiRs), whose biological relevance is
      often unclear. We found that mature miR-21, the most widely researched miRNA
      because of its importance in human disease, is produced in two prevalent isomiR
      forms that differ by 1 nt at their 3' end, and moreover that the 3' end of miR-21
      is posttranscriptionally adenylated by the noncanonical poly(A) polymerase PAPD5.
      PAPD5 knockdown caused an increase in the miR-21 expression level, suggesting
      that PAPD5-mediated adenylation of miR-21 leads to its degradation.
      Exoribonuclease knockdown experiments followed by small-RNA sequencing suggested
      that PARN degrades miR-21 in the 3'-to-5' direction. In accordance with this
      model, microarray expression profiling demonstrated that PAPD5 knockdown results
      in a down-regulation of miR-21 target mRNAs. We found that disruption of the miR
      21 adenylation and degradation pathway is a general feature in tumors across a
      wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well
      as in the noncancerous proliferative disease psoriasis. We conclude that PAPD5
      and PARN mediate degradation of oncogenic miRNA miR-21 through a tailing and
      trimming process, and that this pathway is disrupted in cancer and other
      proliferative diseases. 

PMID- 25049418
TI  - Sulfenome mining in Arabidopsis thaliana.
AB  - Reactive oxygen species (ROS) have been shown to be potent signaling molecules.
      Today, oxidation of cysteine residues is a well-recognized posttranslational
      protein modification, but the signaling processes steered by such oxidations are
      poorly understood. To gain insight into the cysteine thiol-dependent ROS
      signaling in Arabidopsis thaliana, we identified the hydrogen peroxide (H2O2)
      dependent sulfenome: that is, proteins with at least one cysteine thiol oxidized
      to a sulfenic acid. By means of a genetic construct consisting of a fusion
      between the C-terminal domain of the yeast (Saccharomyces cerevisiae) AP-1-like
      (YAP1) transcription factor and a tandem affinity purification tag, we detected ~
      100 sulfenylated proteins in Arabidopsis cell suspensions exposed to H2O2 stress.
      The in vivo YAP1-based trapping of sulfenylated proteins was validated by a
      targeted in vitro analysis of dehydroascorbate reductase2 (DHAR2). In DHAR2, the
      active site nucleophilic cysteine is regulated through a sulfenic acid-dependent
      switch, leading to S-glutathionylation, a protein modification that protects the
      protein against oxidative damage.

PMID- 25049419
TI  - Auxin transport sites are visualized in planta using fluorescent auxin analogs.
AB  - The plant hormone auxin is a key morphogenetic signal that controls many aspects
      of plant growth and development. Cellular auxin levels are coordinately regulated
      by multiple processes, including auxin biosynthesis and the polar transport and
      metabolic pathways. The auxin concentration gradient determines plant organ
      positioning and growth responses to environmental cues. Auxin transport systems
      play crucial roles in the spatiotemporal regulation of the auxin gradient. This
      auxin gradient has been analyzed using SCF-type E3 ubiquitin-ligase complex-based
      auxin biosensors in synthetic auxin-responsive reporter lines. However, the
      contributions of auxin biosynthesis and metabolism to the auxin gradient have
      been largely elusive. Additionally, the available information on subcellular
      auxin localization is still limited. Here we designed fluorescently labeled auxin
      analogs that remain active for auxin transport but are inactive for auxin
      signaling and metabolism. Fluorescent auxin analogs enable the selective
      visualization of the distribution of auxin by the auxin transport system.
      Together with auxin biosynthesis inhibitors and an auxin biosensor, these analogs
      indicated a substantial contribution of local auxin biosynthesis to the formation
      of auxin maxima at the root apex. Moreover, fluorescent auxin analogs mainly
      localized to the endoplasmic reticulum in cultured cells and roots, implying the
      presence of a subcellular auxin gradient in the cells. Our work not only provides
      a useful tool for the plant chemical biology field but also demonstrates a new
      strategy for imaging the distribution of small-molecule hormones. 

PMID- 25049420
TI  - Improving fatty acids production by engineering dynamic pathway regulation and
      metabolic control.
AB  - Global energy demand and environmental concerns have stimulated increasing
      efforts to produce carbon-neutral fuels directly from renewable resources.
      Microbially derived aliphatic hydrocarbons, the petroleum-replica fuels, have
      emerged as promising alternatives to meet this goal. However, engineering
      metabolic pathways with high productivity and yield requires dynamic
      redistribution of cellular resources and optimal control of pathway expression.
      Here we report a genetically encoded metabolic switch that enables dynamic
      regulation of fatty acids (FA) biosynthesis in Escherichia coli. The engineered
      strains were able to dynamically compensate the critical enzymes involved in the
      supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward
      FA biosynthesis. Implementation of this metabolic control resulted in an
      oscillatory malonyl-CoA pattern and a balanced metabolism between cell growth and
      product formation, yielding 15.7- and 2.1-fold improvement in FA titer compared
      with the wild-type strain and the strain carrying the uncontrolled metabolic
      pathway. This study provides a new paradigm in metabolic engineering to control
      and optimize metabolic pathways facilitating the high-yield production of other
      malonyl-CoA-derived compounds. 

PMID- 25049421
TI  - Gerald Maurice Edelman.

PMID- 25049423
TI  - QnAs with Fred Gage.

PMID- 25049422
TI  - Satiety factor oleoylethanolamide recruits the brain histaminergic system to
      inhibit food intake.
AB  - Key factors driving eating behavior are hunger and satiety, which are controlled
      by a complex interplay of central neurotransmitter systems and peripheral
      stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by
      enterocytes in response to fat intake and indirectly signals satiety to
      hypothalamic nuclei. Brain histamine is released during the appetitive phase to
      provide a high level of arousal in anticipation of feeding, and mediates satiety.
      However, despite the possible functional overlap of satiety signals, it is not
      known whether histamine participates in OEA-induced hypophagia. Using different
      experimental settings and diets, we report that the anorexiant effect of OEA is
      significantly attenuated in mice deficient in the histamine-synthesizing enzyme
      histidine decarboxylase (HDC-KO) or acutely depleted of histamine via
      interocerebroventricular infusion of the HDC blocker alpha-fluoromethylhistidine
      (alpha-FMH). alpha-FMH abolished OEA-induced early occurrence of satiety onset
      while increasing histamine release in the CNS with an H3 receptor antagonist
      increased hypophagia. OEA augmented histamine release in the cortex of fasted
      mice within a time window compatible to its anorexic effects. OEA also increased
      c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but
      not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain
      regions that receive histaminergic innervation and participate in the expression
      of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results
      demonstrate that OEA requires the integrity of the brain histamine system to
      fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are
      the likely hypothalamic area where brain histamine influences the central effects
      of OEA. 

PMID- 25049424
TI  - Positive deviance: a different approach to achieving patient safety.

PMID- 25049425
TI  - Role of pigment epithelium-derived factor in the reproductive system.
AB  - The physiological function of the female reproductive organs is hormonally
      controlled. In each cycle, the reproductive organs undergo tissue modifications
      that are accompanied by formation and destruction of blood vessels. Proper
      angiogenesis requires an accurate balance between stimulatory and inhibitory
      signals, provided by pro- and anti-angiogenic factors. As with many other
      tissues, vascular endothelial growth factor (VEGF) appears to be one of the major
      pro-angiogenic factors in the female reproductive organs. Pigment epithelium
      derived factor (PEDF) is a non-inhibitory member of the serine protease
      inhibitors (serpin) superfamily, possessing potent physiologic anti-angiogenic
      activity that negates VEGF activity. The role of PEDF in decreasing abnormal
      neovascularization by exerting its anti-angiogenic effect that inhibits pro
      angiogenic factors, including VEGF, has been investigated mainly in the eye and
      in cancer. This review summarizes the function of PEDF in the reproductive
      system, showing its hormonal regulation and its anti-angiogenic activity.
      Furthermore, some pathologies of the female reproductive organs, including
      endometriosis, ovarian hyperstimulation syndrome, polycystic ovary syndrome, and
      others, are associated with a faulty angiogenic process. This review illuminates
      the role of PEDF in their pathogenesis and treatment. Collectively, we can
      conclude that although PEDF seems to play an essential role in the physiology and
      pathophysiology of the reproductive system, its full role and mechanism of action
      still need to be elucidated. 

PMID- 25049426
TI  - Porcine sperm capacitation involves tyrosine phosphorylation and activation of
      aldose reductase.
AB  - Mammalian sperm must be activated in the tubal isthmus through capacitation to
      induce the acrosome reaction and subsequent fertilization. Although the molecular
      mechanisms involved in capacitation have yet to be fully elucidated, increased
      concentrations of reactive oxygen species (ROS) and the extent of tyrosine
      phosphorylation of proteins have been suggested to play central roles in the
      completion of capacitation. In this study, aldose reductase was for the first
      time identified as one of the tyrosine-phosphorylated proteins involved in the
      capacitation of porcine cauda epididymal sperm. Both tyrosine phosphorylation and
      activity of aldose reductase associated with the particulate fraction of sperm
      cells were significantly enhanced during capacitation. Alrestatin, a membrane
      permeable and specific inhibitor of aldose reductase, plays a role in the
      inhibition of aldose reductase activity, elevation of intracellular levels of
      ROS, and induction of hyperactivated motility, all at similar dose dependencies.
      Alrestatin canceled both the increase in the tyrosine phosphorylation of aldose
      reductase and the decrease in the glutathione levels in sperm-induced during
      capacitation. The hyperactivated motility was induced to a higher extent in the
      presence of glucose than in the presence of fructose. These results indicate that
      aldose reductase plays an important role in induction of hyperactivation and
      capacitation of sperm through the elevation of ROS in sperm cells. Furthermore,
      aldose reductase was shown to be added to sperm during transit through the
      epididymis, suggesting that aldose reductase is one of the key proteins that
      support the functional maturation of sperm. 

PMID- 25049427
TI  - When less is more: T lymphocyte populations with restricted antigen receptor
      diversity.

PMID- 25049428
TI  - Pillars article: analysis of T cell antigen receptor (TCR) expression by human
      peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of
      several Vbeta genes and an invariant TCR alpha chain. J. Exp. Med. 1993. 178: 1
      16.

PMID- 25049429
TI  - Pillars article: homogenous junctional sequence of the V14+ T-cell antigen
      receptor alpha chain expanded in unprimed mice. Proc. Natl. Acad. Sci. U.S.A.
      1990. 87: 5248-5252.

PMID- 25049431
TI  - Dendritic cell-derived exosomes as immunotherapies in the fight against cancer.
AB  - Exosomes are nanometric membrane vesicles of late endosomal origin released by
      most, if not all, cell types as a means of sophisticated intercellular
      communication. A multitude of studies showed how exosomes can mediate and
      regulate immune responses against tumors. Dendritic cell-derived exosomes (Dex)
      have received much attention as immunotherapeutic anticancer agents since the
      discovery that they harbor functional MHC-peptide complexes, in addition to
      various other immune-stimulating components, that together facilitate immune cell
      dependent tumor rejection. The therapeutic potential of Dex has been
      substantiated with their development and clinical testing in the treatment of
      cancer. This review focuses on mechanisms by which Dex interact with and
      influence immune cells and describes how they can be engineered to promote their
      immunogenic capacity as novel and dynamic anticancer agents. 

PMID- 25049430
TI  - Roles and regulation of gastrointestinal eosinophils in immunity and disease.
AB  - Eosinophils have historically been considered to be destructive end-stage
      effector cells that have a role in parasitic infections and allergic reactions by
      the release of their granule-derived cytotoxic proteins. However, an increasing
      number of experimental observations indicate that eosinophils also are
      multifunctional leukocytes involved in diverse inflammatory and physiologic
      immune responses. Under homeostatic conditions, eosinophils are particularly
      abundant in the lamina propria of the gastrointestinal tract, where their
      involvement in various biological processes within the gastrointestinal tract has
      been posited. In this review, we summarize the molecular steps involved in
      eosinophil development and describe eosinophil trafficking to the
      gastrointestinal tract. We synthesize the current findings on the phenotypic and
      functional properties of gastrointestinal eosinophils and the accumulating
      evidence that they have a contributory role in gastrointestinal disorders, with a
      focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the
      potential role of eosinophils as modulators of the intestinal immune system. 

PMID- 25049437
TI  - Closing the Social Class Achievement Gap for First-Generation Students in
      Undergraduate Biology.
AB  - Many students start college intending to pursue a career in the biosciences, but
      too many abandon this goal because they struggle in introductory biology.
      Interventions have been developed to close achievement gaps for underrepresented
      minority students and women, but no prior research has attempted to close the gap
      for first-generation students, a population that accounts for nearly a fifth of
      college students. We report a values affirmation intervention conducted with 798
      U.S. students (154 first-generation) in an introductory biology course for
      majors. For first-generation students, values affirmation significantly improved
      final course grades and retention in the second course in the biology sequence,
      as well as overall GPA for the semester. This brief intervention narrowed the
      achievement gap between first-generation and continuing generation students for
      course grades by 50% and increased retention in a critical gateway course by 20%.
      Our results suggest that educators can expand the pipeline for first-generation
      students to continue studying in the biosciences with psychological
      interventions.

PMID- 25049438
TI  - Urinary N-acetyl-beta-D-glucosaminidase as an early marker for acute kidney
      injury in full-term newborns with neonatal hyperbilirubinemia.
AB  - PURPOSE: To investigate renal function estimated by markers in full-term newborns
      with hyperbilirubinemia. METHODS: A total of 332 full-term newborns with
      hyperbilirubinemia and 60 healthy full-term newborns were enrolled. Total serum
      bilirubin, serum creatinine (Cr), serum blood urea nitrogen (BUN), serum cystatin
      C (Cys-C), urinary beta-2-microglobulin (beta 2MG) index, and urinary N-acetyl
      beta-D-glucosaminidase (NAG) index were measured before and after treatment. All
      newborns were divided into three groups according to total serum bilirubin
      levels: group 1 (221-256), group 2 (256-342), and group 3 (>342). RESULTS: The
      control group and group 1 did not differ significantly in regard to serum Cr,
      serum BUN, serum Cys-C, urinary beta 2MG index, and urinary NAG index. Urinary
      NAG index in group 2 was significantly higher than that in control group (P <
      0.001). Between control group and group 3, serum Cys-C, urinary beta 2MG index,
      and urinary NAG index differed significantly. The significant positive
      correlation between total serum bilirubin and urinary NAG index was found in
      newborns when total serum bilirubin level was more than 272 MUmol/L. CONCLUSIONS:
      High unconjugated bilirubin could result in acute kidney injury in full-term
      newborns. Urinary NAG might be the suitable marker for predicting acute kidney
      injury in full-term newborns with hyperbilirubinemia.

PMID- 25049440
TI  - The accuracy of the compressible Reynolds equation for predicting the local
      pressure in gas-lubricated textured parallel slider bearings.
AB  - The validity of the compressible Reynolds equation to predict the local pressure
      in a gas-lubricated, textured parallel slider bearing is investigated. The local
      bearing pressure is numerically simulated using the Reynolds equation and the
      Navier-Stokes equations for different texture geometries and operating
      conditions. The respective results are compared and the simplifying assumptions
      inherent in the application of the Reynolds equation are quantitatively
      evaluated. The deviation between the local bearing pressure obtained with the
      Reynolds equation and the Navier-Stokes equations increases with increasing
      texture aspect ratio, because a significant cross-film pressure gradient and a
      large velocity gradient in the sliding direction develop in the lubricant film.
      Inertia is found to be negligible throughout this study.

PMID- 25049439
TI  - Serum levels of resistin, adiponectin, and apelin in gastroesophageal cancer
      patients.
AB  - The aim of the study was the investigation of relationship between cachexia
      syndrome and serum resistin, adiponectin, and apelin in patients with
      gastroesophageal cancer (GEC). MATERIAL AND METHODS: Adipocytokines
      concentrations were measured in sera of 85 GEC patients and 60 healthy controls.
      They were also evaluated in tumor tissue and appropriate normal mucosa of 38
      operated cancer patients. RESULTS: Resistin and apelin concentrations were
      significantly higher in GEC patients than in the controls. The highest resistin
      levels were found in cachectic patients and in patients with distant metastasis.
      Serum adiponectin significantly decreased in GEC patients with regional and
      distant metastasis. Serum apelin was significantly higher in cachectic patients
      than in the controls. Apelin was positively correlated with hsCRP level. Resistin
      and apelin levels increased significantly in tumor tissues. Weak positive
      correlations between adipocytokines levels in serum and in tumor tissue were
      observed. CONCLUSIONS: Resistin is associated with cachexia and metastasis
      processes of GEC. Reduction of serum adiponectin reflects adipose tissue wasting
      in relation to GEC progression. Correlation of apelin with hsCRP can reflect a
      presumable role of apelin in systemic inflammatory response in esophageal and
      gastric cancer.

PMID- 25049441
TI  - Designing prosthetic knee joints with bio-inspired bearing surfaces.
AB  - It has long been known that articular cartilage exhibits a surface microtexture
      with shallow indentations. By contrast, prosthetic joints consist of ultra-smooth
      bearing surfaces, the longevity of which does not reach that of natural
      cartilage. We show that adding a microtexture to the smooth femoral component of
      a prosthetic knee joint reduces friction by increasing the lubricant film
      thickness between the bearing surfaces of the knee. We have implemented an
      elastohydrodynamic lubrication model to optimize the geometry of the
      microtexture, while taking into account the deformation of the polyethylene
      tibial insert. We have manufactured several microtexture designs on a surrogate
      femoral component, and experimentally demonstrate that the microtexture reduces
      friction between the surrogate femoral component and tibial insert.

PMID- 25049442
TI  - Evolution of a specialty: the case for the association of chiefs of
      interventional radiology.

PMID- 25049443
TI  - Complications of image-guided thermal ablation of liver and kidney neoplasms.
AB  - Image-guided thermal ablation is a widely accepted tool in the treatment of a
      variety of solid organ neoplasms. Among the different techniques of ablation,
      radiofrequency ablation, cryoablation, and microwave ablation have been most
      commonly used and investigated in the treatment of liver and kidney neoplasms.
      This article will review complications following thermal ablation of tumors in
      the liver and kidney, and discuss the risks and clinical presentation of each
      complication as well as how to treat and potentially avoid complications. 

PMID- 25049444
TI  - Image-guided ablation of adrenal lesions.
AB  - Although laparoscopic adrenalectomy has remained the standard of care for the
      treatment for adrenal tumors, percutaneous image-guided ablation therapy, such as
      chemical ablation, radiofrequency ablation, cryoablation, and microwave ablation,
      has been shown to be clinically useful in many nonsurgical candidates. Ablation
      therapy has been used to treat both functioning adenomas and malignant tumors,
      including primary adrenal carcinoma and metastasis. For patients with functioning
      adenomas, biochemical and symptomatic improvement is achieved in 96 to 100% after
      ablation; for patients with malignant adrenal neoplasms, however, the survival
      benefit from ablation therapy remains unclear, though good initial results have
      been reported. This article outlines the current role of ablation therapy for
      adrenal lesions, as well as identifying some of the technical considerations for
      this procedure. 

PMID- 25049445
TI  - Renal ablation update.
AB  - Thermal ablative technologies have evolved considerably in the recent past and
      are now an important component of current clinical guidelines for the treatment
      of small renal masses. Both radiofrequency ablation and cryoablation have
      intermediate-term oncologic control that rivals surgical options, with favorable
      complication profiles. Studies comparing cryoablation and radiofrequency ablation
      show no significant difference in oncologic control or complication profile
      between the two modalities. Early data from small series with microwave ablation
      have shown similar promising results. Newer technologies including irreversible
      electroporation and high-intensity-focused ultrasound have theoretical
      advantages, but will require further research before becoming a routine part of
      the ablation armamentarium. The purpose of this review article is to discuss the
      current ablative technologies available, briefly review their mechanisms of
      action, discuss technical aspects of each, and provide current data supporting
      their use. 

PMID- 25049446
TI  - The Role of PET Imaging Before, During, and After Percutaneous Hepatic and
      Pulmonary Tumor Ablation.
AB  - The combination of anatomic and metabolic information provided by positron
      emission tomography (PET)/computed tomography makes it an important imaging
      modality to be obtained in conjunction with percutaneous ablation of primary and
      secondary malignancies of the lungs and liver. Advantages include more accurate
      preprocedural staging to determine appropriate treatment options, intraprocedural
      guidance to target difficult-to-see lesions, and postprocedural detection of
      residual or recurrent disease. Future applications of PET include strategies for
      intraprocedural guidance with real-time determination of incompletely ablated
      tumor, and combined PET/magnetic resonance imaging before, during, and after
      ablation for greater sensitivity to detect disease. 

PMID- 25049448
TI  - Multiple arteries supplying a single tumor vascular distribution: microsphere
      administration options for the interventional radiologist performing
      radioembolization.

PMID- 25049447
TI  - Percutaneous image-guided ablation of breast tumors: an overview.
AB  - Percutaneous non-surgical image-guided ablation is emerging as an adjunct or
      alternative to surgery in the management of benign and malignant breast tumors.
      This review covers the current state of the literature regarding percutaneous
      image-guided ablation modalities, clinical factors regarding patient selection,
      and future directions for research. 

PMID- 25049449
TI  - What is too big? Uterine artery embolization of a large fibroid causing abdominal
      compartment syndrome.

PMID- 25049450
TI  - Apathy and emotion-based decision-making in amnesic mild cognitive impairment and
      Alzheimer's disease.
AB  - BACKGROUND: Apathy and reduced emotion-based decision-making are two behavioral
      modifications independently described in Alzheimer's disease (AD) and amnestic
      mild cognitive impairment (aMCI). OBJECTIVES: The aims of this study were to
      investigate decision-making based on emotional feedback processing in AD and aMCI
      and to study the impact of reduced decision-making performances on apathy.
      METHODS: We recruited 20 patients with AD, 20 participants with aMCI, and 20
      healthy controls. All participants completed the Lille apathy rating scale (LARS)
      and the Iowa gambling task (IGT). RESULTS: Both aMCI and AD participants had
      reduced performances on the IGT and were more apathetic compared to controls
      without any difference between aMCI and AD groups. For the entire sample, LARS
      initiation dimension was related to IGT disadvantageous decision-making profile.
      CONCLUSIONS: We provide the first study showing that both aMCI and AD individuals
      make less profitable decisions than controls, whereas aMCI and AD did not differ.
      Disadvantageous decision-making profile on the IGT was associated with higher
      level of apathy on the action initiation dimension. The role of an abnormal IGT
      performance as a risk factor for the development of apathy needs to be
      investigated in other clinical populations and in normal aging.

PMID- 25049451
TI  - Blood injury and injection phobia: the neglected one.
AB  - Blood injury and injection (BII) phobia is a unique phobia associated with a
      diphasic cardiovascular response. The aim of this survey was to report the
      prevalence of BII phobia, its heritability, and clinical characteristics among
      the males and females in the Indian subcontinent. An interview and a survey were
      conducted using a developed BII phobia 21-item questionnaire among 3261
      participant males (n = 1648) and females (n = 1613). Cronbach' alpha (alpha) of
      0.972 of internal consistency was reported. The prevalence of BII phobia and
      associated fainting in females was slightly more than double in the males with a
      significant gender related effect. Similar avoidance behaviours involving
      hospital visits were reported for both males and females. The relative frequency
      of BII phobia among first and third degree relatives was found to be higher than
      among second degree relatives. Depression was found highly comorbid with BII
      phobia while a low rate of obsessive compulsion disorder (OCD) and social anxiety
      disorder (SAD) was reported. Morbidity associated with BII phobia may increase
      dramatically when other medical problems coincide with it. 

PMID- 25049452
TI  - Negative emotions in migraineurs dreams: the increased prevalence of oneiric fear
      and anguish, unrelated to mood disorders.
AB  - BACKGROUND: Migraineurs brain has shown some functional peculiarities that
      reflect not only in phonophobia, and photophobia, but also in mood and sleep.
      Dreaming is a universal mental state characterized by hallucinatory features in
      which imagery, emotion, motor skills, and memory are created de novo. We
      evaluated dream contents and associated emotions in migraineurs. MATERIALS AND
      METHODS: 412 subjects: 219 controls; and 148 migraineurs (66 with aura, MA; 82
      without aura, MO), and 45 tension type headache patients (TTH). A semistructured
      retrospective self-reported questionnaire was used to evaluate dreams. The
      Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health
      Questionnaire (PHQ-9) were administered to evaluate anxiety and depression.
      RESULTS: Migraineurs showed increased levels of anxiety (P = 0.0002 for MA versus
      controls, P = 0.004 for MO versus controls). Fear and anguish during dreaming
      were more frequently reported by migraine patients compared to controls,
      independently by anxiety and depression scores. DISCUSSION: The brain of
      migraineurs seems to dream with some peculiar features, all with a negative
      connotation, as fear and anguish. It may be due to the recorded negative
      sensations induced by recurrent migraine pain, but it may just reflect a peculiar
      attitude of the mesolimbic structures of migraineurs brain, activated in both
      dreaming and migraine attacks.

PMID- 25049454
TI  - Evaluation of plant-mediated Silver nanoparticles synthesis and its application
      in postharvest Physiology of cut Flowers.
AB  - Today the use of silver nanoparticles is becoming increasingly widespread due to
      their wide applications as antimicrobial agent. Green synthesis of silver
      nanoparticles (SNPs) using the petal extract of saffron (Crocus sativus) as a
      reducing agent from 5 mM AgNO3 has been investigated in this work. Diverse petal
      extracts quantities and reaction times were used for the synthesis of SNPs. The
      resulting SNPs were characterized by means of UV-Vis, XRD and FTIR techniques.
      SNPs were synthesized rapidly within 30 min of incubation period and synthesized
      SNPs showed an absorption peak at 380-400 nm in the UV-Vis spectrum. XRD spectrum
      confirmed the formation of metallic silver, too. Green synthesized SNPs were used
      as antimicrobial agent against three bacterial genera of Bacillus, Pseudomonas
      and Acinetobacter which contaminate preservative solution of cut-flowers, too.
      According to the results biosynthesized SNPs using saffron petals successfully
      controlled these bacteria and have made them promising candidates as new
      generation of antimicrobials. This route is rapid, simple without any hazardous
      chemicals and economical to synthesized SNPs. 

PMID- 25049455
TI  - Utilization of (15)NO3 (-) by nodulated soybean plants under conditions of root
      hypoxia.
AB  - Waterlogging of soils is common in nature. The low availability of oxygen under
      these conditions leads to hypoxia of the root system impairing the development
      and productivity of the plant. The presence of nitrate under flooding conditions
      is regarded as being beneficial towards tolerance to this stress. However, it is
      not known how nodulated soybean plants, cultivated in the absence of nitrate and
      therefore not metabolically adapted to this compound, would respond to nitrate
      under root hypoxia in comparison with non-nodulated plants grown on nitrate. A
      study was conducted with (15)N labelled nitrate supplied on waterlogging for a
      period of 48 h using both nodulated and non-nodulated plants of different
      physiological ages. Enrichment of N was found in roots and leaves with
      incorporation of the isotope in amino acids, although to a much smaller degree
      under hypoxia than normoxia. This demonstrates that nitrate is taken up under
      hypoxic conditions and assimilated into amino acids, although to a much lesser
      extent than for normoxia. The similar response obtained with nodulated and non
      nodulated plants indicates the rapid metabolic adaptation of nodulated plants to
      the presence of nitrate under hypoxia. Enrichment of N in nodules was very much
      weaker with a distinct enrichment pattern of amino acids (especially asparagine)
      suggesting that labelling arose from a tissue source external to the nodule
      rather than through assimilation in the nodule itself. 

PMID- 25049453
TI  - The regulatory role of activating transcription factor 2 in inflammation.
AB  - Activating transcription factor 2 (ATF2) is a member of the leucine zipper family
      of DNA-binding proteins and is widely distributed in tissues including the liver,
      lung, spleen, and kidney. Like c-Jun and c-Fos, ATF2 responds to stress-related
      stimuli and may thereby influence cell proliferation, inflammation, apoptosis,
      oncogenesis, neurological development and function, and skeletal remodeling.
      Recent studies clarify the regulatory role of ATF2 in inflammation and describe
      potential inhibitors of this protein. In this paper, we summarize the properties
      and functions of ATF2 and explore potential applications of ATF2 inhibitors as
      tools for research and for the development of immunosuppressive and anti
      inflammatory drugs. 

PMID- 25049456
TI  - Nitric oxide increases tolerance responses to moderate water deficit in leaves of
      Phaseolus vulgaris and Vigna unguiculata bean species.
AB  - Drought stress is one of the most intensively studied and widespread constraints,
      and nitric oxide (NO) is a key signaling molecule involved in the mediation of
      abiotic stresses in plants. We demonstrated that a sprayed solution of NO from
      donor sodium nitroprusside increased drought stress tolerance responses in both
      sensitive (Phaseolus vulgaris) and tolerant (Vigna unguiculata) beans. In intact
      plants subjected to halting irrigation, NO increased the leaf relative water
      content and stomatal conductance in both species. After cutting leaf discs and
      washing them, NO induced increased electrolyte leakage, which was more evident in
      the tolerant species. These leaf discs were then subjected to different water
      deficits, simulating moderate and severe drought stress conditions through
      polyethylene glycol solutions. NO supplied at moderate drought stress revealed a
      reduced membrane injury index in sensitive species. In hydrated discs and at this
      level of water deficit, NO increased the electron transport rate in both species,
      and a reduction of these rates was observed at severe stress levels. Taken
      together, it can be shown that NO has an effective role in ameliorating drought
      stress effects, activating tolerance responses at moderate water deficit levels
      and in both bean species which present differential drought tolerance. 

PMID- 25049457
TI  - Halopriming of seeds imparts tolerance to NaCl and PEG induced stress in Vigna
      radiata (L.) Wilczek varieties.
AB  - The investigation was carried out to study the effect of halopriming on NaCl and
      polyethylene glycol-6000 (PEG-6000) induced stress tolerance potential of three
      Vigna radiata (L.) Wilczek varieties, with varied abiotic stress tolerance
      potential. Halopriming is a seed priming technique in which the seeds were soaked
      in various salt solutions (in this study NaCl was used). The results of the study
      indicated that the application of stresses (both NaCl and PEG) induced
      retardation of growth attributes (measured in terms of shoot length, fresh
      weight, dry weight) and decrease in physiological attributes like total
      chlorophyll content, metabolites, photosynthetic and mitochondrial activity of
      the seedlings in all three V. radiata (L.) varieties. However, halopriming of the
      seeds could reduce the extent of decrease in these biological attributes. NaCl
      and PEG stress also caused increase in MDA content (a product of membrane lipid
      peroxidation) in all the varieties studied and this increase was significantly
      minimized under halopriming. From the present investigation it was evident that
      among the green gram varieties studied, Pusa Vishal, a NaCl tolerant variety
      showed enhanced tolerance to NaCl and PEG induced stress, when the seeds were
      subjected to halopriming followed by Pusa Ratna (stress sensitive variety). Pusa
      9531 (drought tolerant variety) also showed positive halopriming effects but it
      was less significant when compared to other two varieties. It could be concluded
      that halopriming improved the drought and salinity stress tolerance potential of
      all varieties and it was significantly higher in the Pusa Vishal as compared to
      Pusa 9531 and Pusa Ratna. 

PMID- 25049458
TI  - Single strand conformation polymorphism of genomic and EST-SSRs marker and its
      utility in genetic evaluation of sugarcane.
AB  - Sugarcane is an important crop producing around 75 % of sugar in world and used
      as first generation biofuel. In present study, the genomic and gene based
      microsatellite markers were analyzed by low cost Single Strand Confirmation
      Polymorphism technique for genetic evaluation of 22 selected sugarcane genotypes.
      Total 16 genomic and 12 Expression Sequence Tag derived markers were able to
      amplify the selected sugarcane genotypes. Total 138 alleles were amplified of
      which 99 alleles (72 %) found polymorphic with an average of 4.9 alleles per
      locus. Microsatellite marker, VCSSR7 and VCSSR 12 showed monomorphic alleles with
      frequency 7.1 % over the average of 3.5 obtained for polymorphic locus. The level
      of Polymorphic Information Content (PIC) varied from 0.09 in VCSSR 6 to 0.88 in
      VCSSR 11 marker respectively with a mean of 0.49. Genomic SSRs showed more
      polymorphism than EST-SSRs markers on selected sugarcane genotypes whereas, the
      genetic similarity indices calculated by Jaccard's similarity coefficient varied
      from 0.55 to 0.81 indicate a high level of genetic similarity among the genotypes
      that was mainly attributed to intra specific diversity. Hence, the SSR-SSCP
      technique helped to identify the genetically diverse clones which could be used
      in crossing program for introgression of sugar and stress related traits in
      hybrid sugarcane. 

PMID- 25049459
TI  - Genome-wide survey of Alternative Splicing in Sorghum Bicolor.
AB  - Sorghum bicolor is a member of grass family which is an attractive model plant
      for genome study due to interesting genome features like low genome size. In this
      research, we performed comprehensive investigation of Alternative Splicing and
      ontology aspects of genes those have undergone these events in sorghum bicolor.
      We used homology based alignments between gene rich transcripts, represented by
      tentative consensus (TC) transcript sequences, and genomic scaffolds to deduce
      the structure of genes and identify alternatively spliced transcripts in sorghum.
      Using homology mapping of assembled expressed sequence tags with genomics data,
      we identified 2,137 Alternative Splicing events in S. bicolor. Our study showed
      that complex events and intron retention are the main types of Alternative
      Splicing events in S. bicolor and highlights the prevalence of splicing site
      recognition for definition of introns in this plant. Annotations of the
      alternatively spliced genes revealed that they represent diverse biological
      process and molecular functions, suggesting a fundamental role for Alternative
      Splicing in affecting the development and physiology of S. bicolor. 

PMID- 25049460
TI  - Phylogenetic analysis of heterocystous cyanobacteria (Subsections IV and V) using
      highly iterated palindromes as molecular markers.
AB  - Highly iterated palindromes (HIP) have been used as high resolution molecular
      markers for assessing the genetic variability and phylogenetic relatedness of
      heterocystous cyanobacteria (subsections IV and V) representing 12 genera of
      heterocystous cyanobacteria, collected from different geographical areas of
      India. DNA fingerprints generated using four HIP markers viz. HIP-AT, HIP-CA, HIP
      GC, and HIP-TG showed 100 % polymorphism in all the heterocystous cyanobacteria
      studied and each marker produced unique and strain-specific banding pattern.
      Furthermore, phylogenetic affinities based on the dendrogram constructed using
      HIP DNA profiles of heterocystous cyanobacteria suggest the monophyletic origin
      of this entire heterocystous clade along with a clear illustration of the
      polyphyletic origin of the branched Stigonematalean order (Subsection V). In
      addition, phylogenetic affinities were validated by principal component analysis
      of the HIP fingerprints. The overall data obtained by both the phylogeny and
      principal component assessments proved that the entire heterocystous clade was
      intermixed, and there are immediate needs for classificatory reforms that satisfy
      morphological plasticity and environmental concerns. 

PMID- 25049461
TI  - Production of tropan alkaloids in the in vitro and callus cultures of Hyoscyamus
      aureus and their genetic stability assessment using ISSR markers.
AB  - Green wild plants (dirctly before flowering) and seeds of Hyoscyamus aureus were
      collected from natural habitat at Al Qalamon region in Syria. Seeds were surface
      sterilized and cultured in vitro, after 21 days from germination stem-derived
      callus was induced on two different nutrient media. Tropane alkaloids were
      extracted from wild plants and 30 days old in vitro plants and callus, and then
      analyzed using GC-MS. Genetic variation was also studied between the wild and in
      vitro plants and the callus culture lines using twenty ISSR markers. The results
      showed that there were significant variations in tropane alkaloids contents
      between the wild plants, the in vitro plants and the callus culture lines. The
      highest content of hyoscyamine was in callus on line A medium, but the highest
      content of scopolamine was in the wild plants. However, the lowest content of
      tropane alkaloids was in callus on line B medium. Also the ISSR analyses showed
      that there was genetic variation between the wild and in vitro plants and the
      callus culture lines. 

PMID- 25049462
TI  - A reliable and efficient protocol for inducing genetically transformed roots in
      medicinal plant Nepeta pogonosperma.
AB  - Nepeta pogonosperma is an important medicinal plant with anti-inflammatory
      effects. An efficient and reliable transformation system for this plant was
      developed through optimization of several factors which affected the rate of
      Agrobacterium rhizogenes mediated transformation. Five bacterial strains, A4,
      ATCC15834, LBA9402, MSU440 and A13, two explant types, leaves and stems, and
      several co-cultivation media were examined. The maximum rate of hairy root
      induction was obtained from stem explants using MSU440 and ATCC15834 bacterial
      strains. A drastic increase in the frequency of transformation (91 %) was
      observed when MS medium lacking NH4NO3, KH2PO4, KNO3 and CaCl2. Hairy root lines
      were confirmed by polymerase chain reaction (PCR) using primers of the rolB gene.
      According to Southern blot analysis, one T-DNA copy was inserted into each of the
      hairy root lines. In the present study, transgenic hairy roots have been obtained
      trough genetic transformation by A. rhizogenes harbouring two plasmids, the Ri
      plasmid and pBI121 binary vector harbouring gus reporter gene. Expression of the
      gus gene in transgenic hairy root was confirmed by histochemical GUS assay. 

PMID- 25049463
TI  - In vitro propagation and withaferin A production in Withania ashwagandha, a rare
      medicinal plant of India.
AB  - Withania ashwagandha, belonging to the family Solanaceae, is an important
      medicinal herb of India with restricted geographic distribution. It is a rich
      source of withaferin A (WA) and other bioactive withanolides. In the present
      study a rapid in vitro mass propagation protocol of W. ashwagandha was developed
      from nodal explants. Nodal explants were cultured on MS medium supplemented with
      various concentrations and combinations of plant growth regulators (PGRs). The
      highest number of regenerated shoots per ex-plant (33 +/- 2.7) and highest WA
      (13.4 +/- 1.15 mg/g of DW) production was obtained on MS medium supplemented with
      5.0 MUM 6-benzyladenine (BA) and 1.0 MUM Kinetin (Kn). In vitro raised shoots
      were further rooted on half-strength MS medium containing 2.0 MUM Indole-3
      butyric acid (IBA) and analyzed for WA production. The rooted plantlets when
      transferred to poly bags in the greenhouse showed 90 % survival frequency. Levels
      of WA were higher in the in vitro and ex vitro derived shoot and root tissues as
      compared to field grown mother plants. In an attempt to further maximize WA
      production, shoot cultures were further grown in liquid MS medium supplemented
      with 5.0 MUM 6-benzyladenine (BA) and 1.0 MUM Kinetin (Kn). Root cultures were
      grown on half strength MS liquid medium fortified with 2.0 MUM of IBA. WA
      production in the liquid cultures was significantly higher compared to the static
      composition of the same media. This protocol, first of its kind in this plant,
      can be successfully employed for conservation, proliferation and large-scale
      production of WA. The regenerated plants can also be used in traditional medicine
      as an alternative to naturally collected plants. 

PMID- 25049464
TI  - Evaluation of aeroponics for clonal propagation of Caralluma edulis, Leptadenia
      reticulata and Tylophora indica - three threatened medicinal Asclepiads.
AB  - The present study explores the potential of aeroponic system for clonal
      propagation of Caralluma edulis (Paimpa) a rare, threatened and endemic edible
      species, Leptadenia reticulata (Jeewanti), a threatened liana used as promoter of
      health and Tylophora indica (Burm.f.) Merill, a valuable medicinal climber.
      Experiments were conducted to asses the effect of exogenous auxin (naphthalene
      acetic acid, indole-3-butyric acid, indole-3-acetic acid) and auxin
      concentrations (0.0, 0.5, 1, 2, 3, 4 or 5gl(-1)) on various root morphological
      traits of cuttings in the aeroponic chamber. Amongst all the auxins tested,
      significant effects on the length, number and percentage of rooting was observed
      in IBA treated nodal cuttings. Cent per cent of the stem cuttings of C. edulis
      rooted if pre-treated with 2.0 gl(-1) of IBA for 5 min while 97.7 % of the stem
      cuttings of L. reticulata and 93.33 % of stem cuttings of Tylophora indica rooted
      with pre-treatment of 3.0 gl(-1) of IBA for 5 min. Presence of at least two
      leaves on the nodal cuttings of L. reticulata and T. indica was found to be a
      prerequisite for root induction. In all the species, the number of adventitious
      roots per cutting and the percentage of cuttings rooted aeroponically were
      significantly higher than the soil grown stem cuttings. Shoot growth measured in
      terms of shoot length was significantly higher in cuttings rooted aeroponically
      as compared to the cuttings rooted under soil conditions. All the plants sprouted
      and rooted aeroponically survived on transfer to soil. This is the first report
      of clonal propagation in an aeroponic system for these plants. This study
      suggests aeroponics as an economic method for rapid root induction and clonal
      propagation of these three endangered and medicinally important plants which
      require focused efforts on conservation and sustainable utilization. 

PMID- 25049465
TI  - In vitro propagation of female Ephedra foliata Boiss. & Kotschy ex Boiss.: an
      endemic and threatened Gymnosperm of the Thar Desert.
AB  - Ephedra foliata Boiss. & Kotschy ex Boiss., (family - Ephedraceae), is an
      ecologically and economically important threatened Gymnosperm of the Indian Thar
      Desert. A method for micropropagation of E. foliata using nodal explant of mature
      female plant has been developed. Maximum bud-break (90 %) of the explant was
      obtained on MS medium supplemented with 1.5 mg l(-1) of benzyl adenine (BA) +
      additives. Explant produces 5.3 +/- 0.40 shoots from single node with 3.25 +/-
      0.29 cm length. The multiplication of shoots in culture was affected by salt
      composition of media, types and concentrations of plant growth regulators (PGR's)
      and their interactions, time of transfer of the cultures. Maximum number of
      shoots (26.3 +/- 0.82 per culture vessel) were regenerated on MS medium modified
      by reducing the concentration of nitrates to half supplemented with 200 mg l(-1)
      ammonium sulphate {(NH4) 2SO4} (MMS3) + BA (0.25 mg l(-1)), Kinetin (Kin; 0.25 mg
      l(-1)), Indole-3-acetic acid (IAA; 0.1 mg l(-1)) and additives. The in vitro
      produced shoots rooted under ex vitro on soilrite moistened with one-fourth
      strength of MS macro salts in screw cap bottles by treating the shoot base (s)
      with 500 mg l(-1) of Indole-3-butyric acid (IBA) for 5 min. The micropropagated
      plants were hardened in the green house. The described protocol can be applicable
      for (i) large scale plant production (ii) establishment of plants in natural
      habitat and (iii) germplasm conservation of this endemic Gymnosperm of arid
      regions. 

PMID- 25049466
TI  - Rapid in vitro propagation system through shoot tip cultures of Vitex trifolia L.
      an important multipurpose plant of the Pacific traditional Medicine.
AB  - A rapid and efficient plant propagation system through shoot tip explants was
      established in Vitex trifolia L., a medicinally important plant belonging to the
      family Verbenaceae. Multiple shoots were induced directly on Murashige and Skoog
      (MS) medium consisting of different cytokinins, 6-benzyladenine (BA), kinetin
      (Kin) and 2-isopentenyl adenine (2-iP), BA at an optimal concentration of 5.0 MUM
      was most effective in inducing multiple shoots where 90 % explants responded with
      an average shoot number (4.4+/-0.1) and shoot length (2.0+/-0.1 cm) after 6 weeks
      of culture. Inclusion of NAA in the culture medium along with the optimum
      concentration of BA promoted a higher rate of shoot multiplication and length of
      the shoot, where 19.2+/-0.3 well-grown healthy shoots with an average shoot
      length of 4.4+/-0.1 cm were obtained on completion of 12 weeks culture period. Ex
      vitro rooting was achieved best directly in soilrite when basal portion of the
      shoots were treated with 500 MUM indole-3-butyric acid for 15 min which was the
      most effective in inducing roots, as 95 % of the microshoots produced roots.
      Plantlets went through a hardening phase in a controlled plant growth chamber,
      prior to ex-vitro transfer. Micropropagated plants grew well, attained maturity
      and flowered with 92 % survival rate. The results of this study provide the first
      report on in vitro plant regeneration of Vitex trifolia L. using shoot tip
      explants. 

PMID- 25049467
TI  - Identification and analysis of expressed sequence tags present in xylem tissues
      of kelampayan (Neolamarckia cadamba (Roxb.) Bosser).
AB  - The large-scale genomic resource for kelampayan was generated from a developing
      xylem cDNA library. A total of 6,622 high quality expressed sequence tags (ESTs)
      were generated through high-throughput 5' EST sequencing of cDNA clones. The ESTs
      were analyzed and assembled to generate 4,728 xylogenesis unigenes distributed in
      2,100 contigs and 2,628 singletons. About 59.3 % of the ESTs were assigned with
      putative identifications whereas 40.7 % of the sequences showed no significant
      similarity to any sequences in GenBank. Interestingly, most genes involved in
      lignin biosynthesis and several other cell wall biosynthesis genes were
      identified in the kelampayan EST database. The identified genes in this study
      will be candidates for functional genomics and association genetic studies in
      kelampayan aiming at the production of high value forests. 

PMID- 25049468
TI  - Phenology of plants in relation to ambient environment in a subalpine forest of
      Uttarakhand, western Himalaya.
AB  - Observations on phenology of some representative trees, shrubs, under-shrubs and
      herbs in a subalpine forest of Uttarakhand, western Himalaya were recorded. With
      the commencement of favorable growth season in April, occurrence of leaf fall was
      indicatory growth phenomenon in Quercus semecarpifolia, Q. floribunda and Abies
      spectabilis. However, active vegetative growth in herbaceous species starts
      onward April and fruit maturation and seed dehiscence are completed from mid of
      September to October. In general, vegetative growth and reproductive stages in
      majority of the studied species seems to be dependent on adequate moisture
      content and also flowering and fruiting in subalpine plants correlate ambient
      temperature. 

PMID- 25049469
TI  - An efficient in vitro regeneration of Ceropegia noorjahaniae: an endemic and
      critically endangered medicinal herb of the Western Ghats.
AB  - An efficient protocol was developed for the rapid in vitro multiplication of an
      endemic and critically endangered medicinal herb, Ceropegia noorjahaniae Ans.,
      via enhanced axillary bud proliferation from nodal explants. The effects of
      phytohormones [6-benzylaminopurine (BAP), kinetin (Kin) thidiazuron (TDZ), indole
      3-acetic acid (IAA), indole-3-butyric acid (IBA) or alpha-naphthalene acetic acid
      (NAA)] on in vitro regeneration were investigated. The highest number of shoots
      (18.3 +/- 1.3), maximum shoot length (10.1 +/- 0.8 cm) and the highest response
      of shoot induction (95 %) were recorded on MS medium supplemented with 2.0 mg/l
      BAP. Rooting was best achieved on half-strength MS medium augmented with IBA (1.0
      mg/l). Half-strength MS medium supplemented with BAP (4 mg/l) and sucrose (5 %,
      w/v) produced an average of 5.6 flower buds per microshoots with highest (90 %)
      flower bud induction response. The plantlets regenerated in vitro with well
      developed shoot and roots were successfully established in pots containing
      sterile sand and coco peat (1:1) and grown in a greenhouse with 85 % survival
      rate. The regenerated plants did not show any detectable morphological variation.
      The developed method can be successfully employed for large-scale multiplication
      and conservation of C. noorjahaniae. 

PMID- 25049470
TI  - Improving the Proteomic Analysis of Archival Tissue by Using Pressure-Assisted
      Protein Extraction: A Mechanistic Approach.
AB  - Formaldehyde-fixed, paraffin-embedded (FFPE) tissue repositories represent a
      valuable resource for the retrospective study of disease progression and response
      to therapy. However, the proteomic analysis of FFPE tissues has been hampered by
      formaldehyde-induced protein modifications, which reduce protein extraction
      efficiency and may lead to protein misidentification. Here, we demonstrate the
      use of heat augmented with high hydrostatic pressure (40,000 psi) as a novel
      method for the recovery of intact proteins from FFPE tissue. Our laboratory has
      taken a mechanistic approach to developing improved protein extraction protocols,
      by first studying the reactions of formaldehyde with proteins and ways to reverse
      these reactions, then applying this approach to a model system called a "tissue
      surrogate", which is a gel formed by treating high concentrations of cytoplasmic
      proteins with formaldehyde, and finally FFPE mouse liver tissue. Our studies
      indicate that elevated pressure improves the recovery of proteins from FFPE
      tissue surrogates by hydrating and promoting solubilization of highly aggregated
      proteins allowing for the subsequent reversal (by hydrolysis) of formaldehyde
      induced protein adducts and cross-links. When FFPE mouse liver was extracted
      using heat and elevated pressure, there was a 4-fold increase in protein
      extraction efficiency and up to a 30-fold increase in the number of non-redundant
      proteins identified by mass spectrometry, compared to matched tissue extracted
      with heat alone. More importantly, the number of non-redundant proteins
      identified in the FFPE tissue was nearly identical to that of the corresponding
      frozen tissue.

PMID- 25049472
TI  - Detection of QTL for Carcass Quality on Chromosome 6 by Exploiting Linkage and
      Linkage Disequilibrium in Hanwoo.
AB  - The purpose of this study was to improve mapping power and resolution for the QTL
      influencing carcass quality in Hanwoo, which was previously detected on the
      bovine chromosome (BTA) 6. A sample of 427 steers were chosen, which were the
      progeny from 45 Korean proven sires in the Hanwoo Improvement Center, Seosan,
      Korea. The samples were genotyped with the set of 2,535 SNPs on BTA6 that were
      imbedded in the Illumina bovine 50 k chip. A linkage disequilibrium variance
      component mapping (LDVCM) method, which exploited both linkage between sires and
      their steers and population-wide linkage disequilibrium, was applied to detect
      QTL for four carcass quality traits. Fifteen QTL were detected at 0.1% comparison
      wise level, for which five, three, five, and two QTL were associated with carcass
      weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area (LMA), and
      marbling score (Marb), respectively. The number of QTL was greater compared with
      our previous results, in which twelve QTL for carcass quality were detected on
      the BTA6 in the same population by applying other linkage disequilibrium mapping
      approaches. One QTL for LMA was detected on the distal region (110,285,672 to
      110,633,096 bp) with the most significant evidence for linkage (p<10(-5)).
      Another QTL that was detected on the proximal region (33,596,515 to 33,897,434
      bp) was pleiotrophic, i.e. influencing CWT, BFT, and LMA. Our results suggest
      that the LDVCM is a good alternative method for QTL fine-mapping in detection and
      characterization of QTL. 

PMID- 25049471
TI  - Roles of conceptus secretory proteins in establishment and maintenance of
      pregnancy in ruminants.
AB  - Reproduction in ruminant species is a highly complex biological process requiring
      a dialogue between the developing conceptus (embryo-fetus and associated
      placental membranes) and maternal uterus which must be established during the
      peri-implantation period for pregnancy recognition signaling and regulation of
      gene expression by uterine epithelial and stromal cells. The uterus provide a
      microenvironment in which molecules secreted by uterine epithelia and transported
      into the uterine lumen represent histotroph, also known as the secretome, that
      are required for growth and development of the conceptus and receptivity of the
      uterus to implantation by the elongating conceptus. Pregnancy recognition
      signaling as related to sustaining the functional lifespan of the corpora lutea,
      is required to sustain the functional life-span of corpora lutea for production
      of progesterone which is essential for uterine functions supportive of
      implantation and placentation required for successful outcomes of pregnancy. It
      is within the peri-implantation period that most embryonic deaths occur in
      ruminants due to deficiencies attributed to uterine functions or failure of the
      conceptus to develop appropriately, signal pregnancy recognition and/or undergo
      implantation and placentation. The endocrine status of the pregnant ruminant and
      her nutritional status are critical for successful establishment and maintenance
      of pregnancy. The challenge is to understand the complexity of key mechanisms
      that are characteristic of successful reproduction in humans and animals and to
      use that knowledge to enhance fertility and reproductive health of ruminant
      species in livestock enterprises. 

PMID- 25049473
TI  - Association of length of pregnancy with other reproductive traits in dairy
      cattle.
AB  - The experiment involved observations of 2,514 Holstein-Friesian cows to determine
      the effects of environmental factors (cow's age, calving season, weight and sex
      of calves, housing system) and genetic factors on gestation length in dairy
      cattle and the correlation between gestation length and other reproductive traits
      (calving ease, stillbirth rates and placental expulsion). Genetic parameters were
      estimated based on the sires of calved cows (indirect effect) and the sires of
      live-born calves (direct effect). The following factors were found to contribute
      to prolonged gestation: increasing cow's age, male fetuses and growing fetus
      weight. Optimal gestation length was determined in the range of 275-277 days
      based on calving ease and stillbirth rates. The heritability of gestation length
      was estimated at 0.201-0.210 by the direct effect and 0.055-0.073 by the indirect
      effect. The resulting genetic correlations suggest that the efforts to optimize
      (prolong) gestation length could exert an adverse influence on the breeding value
      of bulls by increasing perinatal mortality and calving difficulty. The standard
      errors of the investigated parameters were relatively high, suggesting that any
      attempts to modify gestation length for the purpose of improving calving ease and
      reducing stillbirth rates should be introduced with great caution. 

PMID- 25049474
TI  - Evaluation of Single Nucleotide Polymorphisms (SNPs) Genotyped by the Illumina
      Bovine SNP50K in Cattle Focusing on Hanwoo Breed.
AB  - In the present study, we evaluated the informativeness of SNPs genotyped by the
      Illumina Bovine SNP50K assay in different cattle breeds. To investigate these on
      a genome-wide scale, we considered 52,678 SNPs spanning the whole autosomal and X
      chromosomes in cattle. Our study samples consists of six different cattle breeds.
      Across the breeds approximately 72 and 6% SNPs were found polymorphic and fixed
      or close to fix in all the breeds, respectively. The variations in the average
      minor allele frequency (MAF) were significantly different between the breeds
      studied. The level of average MAF observed in Hanwoo was significantly lower than
      the other breeds. Hanwoo breed also displayed the lowest number of polymorphic
      SNPs across all the chromosomes. More importantly, this study indicated that the
      Bovine SNP50K assay will have reduced power for genome-wide association studies
      in Hanwoo as compared to other cattle breeds. Overall, the Bovine SNP50K assay
      described in this study offer a useful genotyping platform for mapping
      quantitative trait loci (QTLs) in the cattle breeds. The assay data represent a
      vast and generally untapped resource to assist the investigation of the complex
      production traits and the development of marker-assisted selection programs. 

PMID- 25049475
TI  - Genotype and allelic frequencies of a newly identified mutation causing blindness
      in jordanian awassi sheep flocks.
AB  - A total of 423 blood samples were collected (during 2009 and 2010) from all the
      ram holdings at three major Jordanian governmental Awassi breeding stations (Al
      Khanasry, Al-Mushairfa and Al-Fjaje) and two private flocks. All blood samples
      were screened for the presence of mutations at the CNGA3 gene (responsible for
      day blindness in Awassi sheep) using RFLP-PCR. The day blindness mutation was
      detected in all studied flocks. The overall allele and genotype frequencies of
      all studied flocks of the day blindness mutation were 0.088 and 17.49%,
      respectively. The genotype and allele frequencies were higher in station flocks
      than the farmer flocks (0.121, 24.15 and 0.012, 2.32, respectively). Al-Mushairfa
      and Al-Khanasry stations have the highest genotype and allele frequencies for the
      day blindness mutation that were 27.77, 30.00% and 0.14, 0.171, respectively. The
      investigated farmer flocks have low percentages (0.03, 5.88% at Al-Shoubak and
      0.005 and 1.05%, at Al-Karak, respectively for genotype and allele frequencies)
      compared with the breeding stations. Ram culling strategy was applied throughout
      the genotyping period in order to gradually eradicate this newly identified day
      blindness mutation from Jordanian Breeding station, since they annually
      distribute a high percentage of improved rams to farmer's flocks. 

PMID- 25049476
TI  - Melatonin Induced Changes in Specific Growth Rate, Gonadal Maturity, Lipid and
      Protein Production in Nile Tilapia Oreochromis niloticus (Linnaeus 1758).
AB  - We have investigated the effect of melatonin (MLT) on specific growth rate (SGR%
      day(-1)), condition factor (k), gonado-somatic-index (GSI), histological
      structures of gonads, serum as well as gonadal protein and lipid in Nile tilapia
      Oreochromis niloticus. MLT treatment in the dose of 25 MUg/L for three weeks
      reduced SGR% day(-1) (0.9+/-0.04) as compared to control (1.23+/-0.026). The GSI
      value was significantly (p<0.05) reduced to 1.77+/-0.253 from control where it
      was 2.56+/-0.25. Serum protein level increased from 9.33+/-2.90 mg/ml (control)
      to 11.67+/-1.45 mg/ml after MLT treatment while there was depressed serum
      triglycerides (86.16+/-1.078 mg/dl) and cholesterol (126.66+/-0.88 mg/dl) as
      compared to control values where these were 123.0+/-1.23 mg/dl and 132.0+/-1.65
      mg/dl respectively. Histological structure of ovary showed small eggs of early
      perinucleolus stage after MLT treatment while testicular structure of control and
      MLT treated fish was more or less similar. It is concluded that exogenous
      melatonin suppressed SGR% day(-1), GSI, ovarian cellular activity, protein and
      lipid biosynthesis, in tilapia suggesting that melatonin is useful in
      manipulating the gonadal maturity in fishes. 

PMID- 25049477
TI  - Regulation of S100G Expression in the Uterine Endometrium during Early Pregnancy
      in Pigs.
AB  - Calcium ions play an important role in the establishment and maintenance of
      pregnancy, but molecular and cellular regulatory mechanisms of calcium ion action
      in the uterine endometrium are not fully understood in pigs. Previously, we have
      shown that calcium regulatory molecules, transient receptor potential vanilloid
      type 5 (TRPV6) and calbindin-D9k (S100G), are expressed in the uterine
      endometrium during the estrous cycle and pregnancy in a pregnancy status- and
      stage-specific manner, and that estrogen of conceptus origin increases
      endometrial TRPV6 expression. However, regulation of S100G expression in the
      uterine endometrium and conceptus expression of S100G has been not determined
      during early pregnancy. Thus, we investigated regulation of S100G expression by
      estrogen and interleukin-1beta (IL1B) in the uterine endometrium and conceptus
      expression of S100G during early pregnancy in pigs. We obtained uterine
      endometrial tissues from day (D) 12 of the estrous cycle and treated with
      combinations of steroid hormones, estradiol-17beta (E2) and progesterone (P4),
      and increasing doses of IL1B. Real-time RT-PCR analysis showed that E2 and IL1B
      increased S100G mRNA levels in the uterine endometrium, and conceptuses expressed
      S100G mRNA during early pregnancy, as determined by RT-PCR analysis. To determine
      if endometrial expression of S100G mRNA during the implantation period was
      affected by the somatic cell nuclear transfer (SCNT) procedure, we compared S100G
      mRNA levels in the uterine endometrium from gilts with SCNT-derived conceptuses
      with those from gilts with conceptuses derived from natural mating on D12 of
      pregnancy. Real-time RT-PCR analysis showed that levels of S100G mRNA in the
      uterine endometrium from gilts carrying SCNT-derived conceptuses was
      significantly lower than those from gilts carrying conceptuses derived from
      natural mating. These results showed that S100G expression in the uterine
      endometrium was regulated by estrogen and IL1B of conceptus origin, and affected
      by the SCNT procedure during early pregnancy. These suggest that conceptus
      signals regulate S100G, an intracellular calcium transport protein, for the
      establishment of pregnancy in pigs. 

PMID- 25049478
TI  - Ovarian Response to Different Dose Levels of Follicle Stimulating Hormone (FSH)
      in Different Genotypes of Bangladeshi Cattle.
AB  - The experiment was conducted under the Department of Animal Breeding and
      Genetics, Bangladesh Agricultural University (BAU), Mymensingh from June, 2001 to
      December, 2005 in two different locations (Central Cattle Breeding and Dairy Farm
      and Bangladesh Livestock Research Institute in Savar, Dhaka) to observe ovarian
      response to different doses of FSH in three different genotypes of cattle-
      indigenous Local, Pabna cattle and Friesian*Local cross. Five different dose
      levels used were 200, 240, 280, 320 and 360 mg. Ovarian response as corpus luteum
      (CL), recovered embryo (RE) and of transferable embryos (TE) count in Local were
      significant for 320, 280 and 280 mg respectively. In Pabna cattle CL, RE and TE
      count were found significant for 360, 320 and 320 mg respectively. In
      Friesian*Local cross CL, RE and TE count were found significant for 360, 320 and
      320 mg respectively. The excellent quality embryos showed significantly the
      highest yield (1.80+/-0.20) in the 240 and 280 mg FSH levels in Local genotype.
      In Pabna cattle, the highest yield (2.00+/-0.32) was found at FSH level 320 mg.
      In Friesian*Local, the highest yield (2.20+/-0.20) was found at FSH level 280 mg.

PMID- 25049479
TI  - Effects of substituting soybean meal for sunflower cake in the diet on the growth
      and carcass traits of crossbred boer goat kids.
AB  - The present study was conducted to determine the best level of substitution of
      soybean meal by sunflower cake in diets for kids through the evaluation of
      quantitative carcass traits. Thirty-two Boer kids X 1/2 NDB (no defined breed),
      males, non-castrated, with 4 months of age and initial body weight of 15+/-3.2
      kg, were randomly assigned to individual pens. The treatments contained four
      substitution levels of soybean meal by sunflower cake (0, 33, 66 and 100% DM). At
      the end of the experimental period, the animals were slaughtered. There was no
      influence of the treatments on any of the mean values of the evaluated measures
      (p>0.05): 21.78 kg (body weight at slaughter), 8.65 kg (hot carcass weight), 8.59
      kg (cold carcass weight), 40.27% (hot carcass yield), 39.20% (cold carcass
      yield), 7.73 cm(2)(rib eye area), 46.74 cm (carcass outer length), 45.68 cm
      (carcass internal length), 36.92 cm (leg length), 26.04 cm (leg perimeter), 48.66
      cm (hind perimeter), 58.62 cm (thoracic perimeter), 0.20 (carcass compactness
      index), 68.48% (total muscle of the leg), 2.79% (total leg fat), 55.19%
      (subcutaneous leg fat), 28.82% (total bone), 81.66 g (femur weight), 14.88 cm
      (femur length), 0.38 (leg muscularity index), 2.53 (muscle:bone ratio) and 33.42
      (muscle:fat ratio). The substitution of soybean meal by sunflower cake may be
      recommended up to a level of 100% without alterations to quantitative carcass
      traits. 

PMID- 25049480
TI  - Effect of Exogenous Fibrolytic Enzyme Application on the Microbial Attachment and
      Digestion of Barley Straw In vitro.
AB  - The effects of exogenous fibrolytic enzymes (EFE; a mixture of two preparations
      from Trichoderma spp., with predominant xylanase and beta-glucanase activities,
      respectively) on colonization and digestion of ground barley straw and alfalfa
      hay by Fibrobacter succinogenes S85 and Ruminococcus flavefaciens FD1 were
      studied in vitro. The two levels (28 and 280 MUg/ml) of EFE tested and both
      bacteria were effective at digesting NDF of hay and straw. With both substrates,
      more NDF hydrolysis (p<0.01) was achieved with EFE alone at 280 than at 28
      MUg/ml. A synergistic effect (p<0.01) of F. succinogenes S85 and EFE on straw
      digestion was observed at 28 but not 280 MUg/ml of EFE. Strain R. flavefaciens
      FD1 digested more (p<0.01) hay and straw with higher EFE than with lower or no
      EFE, but the effect was additive rather than synergistic. Included in the
      incubation medium, EFE showed potential to improve fibre digestion by
      cellulolytic ruminal bacteria. In a second batch culture experiment using mixed
      rumen microbes, DM disappearance (DMD), gas production and incorporation of (15)N
      into particle-associated microbial N ((15)N-PAMN) were higher (p<0.001) with
      ammoniated (5% w/w; AS) than with native (S) ground barley straw. Application of
      EFE to the straws increased (p<0.001) DMD and gas production at 4 and 12 h, but
      not at 48 h of the incubation. EFE applied onto S increased (p<0.01) (15)N-PAMN
      at 4 h only, but EFE on AS increased (p<0.001) (15)N-PAMN at all time points.
      Prehydrolysis increased (p<0.01) DMD from both S and AS at 4 and 12 h, but
      reduced (p<0.01) (15)N-PAMN in the early stage (4 h) of the incubation, as
      compared to non-prehydrolyzed samples. Application of EFE to barley straw
      increased rumen bacterial colonization of the substrate, but excessive hydrolytic
      action of EFE prior to incubation decreased it. 

PMID- 25049481
TI  - Feeding Unprotected CLA Methyl Esters Compared to Sunflower Seeds Increased Milk
      CLA Level but Inhibited Milk Fat Synthesis in Cows.
AB  - An experiment was conducted to compare the effect of the same amount of 18:2
      offered either as 18:2n-6 or as a mixture of unprotected 18:2c9t11 and 18:2t10c12
      on feed intake, milk components as well as plasma and milk fatty acid profile.
      Fifteen cows were blocked by milk yield and milk fat percentage and within block
      assigned randomly to 1 of 3 treatments (n = 5). Each cow passed a 12-d adjustment
      period (AP) on a basal diet. After the AP cows received 1 of 3 supplements during
      an 18-d experimental period (EP). The supplements contained either 1.0 kg ground
      sunflower seeds (S), 0.5 kg conjugated linoleic acid (CLA)-oil (C) or 0.75 kg of
      a mixture of ground sunflower seeds and CLA-oil (2:1; SC). All 3 supplements
      contained the same amount of 18:2 either as CLA (?18:2c9t11+18:2t10c12, 1:1) or
      as 18:2c9c12. During the last 2 d of AP and the last 4 d of EP feed intake and
      milk yield were recorded daily and milk samples were collected at each milking.
      Blood samples were collected from the jugular vein on d 11 of AP and d 15 and 18
      of EP. The 18:2 intake increased in all treatments from AP to EP. Regardless of
      the amount of supplemented CLA, the milk fat percentage decreased by 2.35 and
      2.10%-units in treatment C and SC, respectively, whereas in the treatment S the
      decrease was with 0.99%-unit less pronounced. Thus, C and SC cows excreted daily
      a lower amount of milk fat than S cows. The concentration of trans 18:1 in the
      plasma and the milk increased from AP to EP and increased with increasing dietary
      CLA supply. While the concentration of 18:2c9t11 and 18:2t10c12 in the plasma and
      that of 18:2t10c12 in the milk paralleled dietary supply, the level of 18:2c9t11
      in the milk was similar in C and CS but still lower in S. Although the dietary
      concentration of CLA was highest in treatment C, the partial replacement of CLA
      by sunflower seeds had a similar inhibitory effect on milk fat synthesis.
      Comparable 18:2c9t11 levels in the milk in both CLA treatments implies that this
      isomer is subjected to greater biohydrogenation with increasing supply than
      18:2t10c12. The fact that unprotected 18:2t10c12 escaped biohydrogenation in
      sufficient amounts to affect milk fat synthesis reveals opportunities to develop
      feeding strategies where reduced milk fat production is desirable or required by
      the metabolic state of the cow. 

PMID- 25049482
TI  - Methane Production of Different Forages in In vitro Ruminal Fermentation.
AB  - An in vitro rumen batch culture study was completed to compare effects of common
      grasses, leguminous shrubs and non-leguminous shrubs used for livestock grazing
      in Australia and Ghana on CH4 production and fermentation characteristics. Grass
      species included Andropodon gayanus, Brachiaria ruziziensis and Pennisetum
      purpureum. Leguminous shrub species included Cajanus cajan, Cratylia argentea,
      Gliricidia sepium, Leucaena leucocephala and Stylosanthes guianensis and non
      leguminous shrub species included Annona senegalensis, Moringa oleifera,
      Securinega virosa and Vitellaria paradoxa. Leaves were harvested, dried at 55
      degrees C and ground through a 1 mm screen. Serum bottles containing 500 mg of
      forage, modified McDougall's buffer and rumen fluid were incubated under
      anaerobic conditions at 39 degrees C for 24 h. Samples of each forage type were
      removed after 0, 2, 6, 12 and 24 h of incubation for determination of cumulative
      gas production. Methane production, ammonia concentration and proportions of VFA
      were measured at 24 h. Concentration of aNDF (g/kg DM) ranged from 671 to 713
      (grasses), 377 to 590 (leguminous shrubs) and 288 to 517 (non-leguminous shrubs).
      After 24 h of in vitro incubation, cumulative gas, CH4 production, ammonia
      concentration, proportion of propionate in VFA and IVDMD differed (p<0.05) within
      each forage type. B. ruziziensis and G. sepium produced the highest cumulative
      gas, IVDMD, total VFA, proportion of propionate in VFA and the lowest A:P ratios
      within their forage types. Consequently, these two species produced moderate CH4
      emissions without compromising digestion. Grazing of these two species may be a
      strategy to reduce CH4 emissions however further assessment in in vivo trials and
      at different stages of maturity is recommended. 

PMID- 25049483
TI  - Effect of Sea Buckthorn Leaves on Inosine Monophosphate and Adenylosuccinatelyase
      Gene Expression in Broilers during Heat Stress.
AB  - The trial was conducted to evaluate the effects of sea buckthorn leaves (SBL) on
      meat flavor in broilers during heat stress. A total 360 one-day-old Arbor Acre
      (AA) broilers (male) were randomly allotted to 4 treatments with 6 replicates
      pens pretreatment and 15 birds per pen. The control group was fed a basal diet,
      the experimental group I, II and III were fed the basal diet supplemented with
      0.25%, 0.5%, 1% SBL, respectively. During the 4th week, broilers were exposed to
      heat stress conditions (36+/-2 degrees C), after which, muscle and liver samples
      were collected. High performance liquid chromatography (HPLC) was performed to
      measure the content of inosine monophosphate (IMP); Real-Time PCR was performed
      to determine the expression of the ADSL gene. The results showed that the content
      of breast muscle IMP of group I, II and III was significantly increased 68%, 102%
      and 103% (p<0.01) compared with the control, respectively; the content of thigh
      muscle IMP of group II and III was significantly increased 56% and 58% (p<0.01),
      respectively. Additionally, ADSL mRNA expression in group I, II and III was
      increased significantly 80%, 65% and 49% (p<0.01) compared with the control,
      respectively. The content of IMP and expression of ADSL mRNA were increased by
      basal diet supplemented with SBL, therefore, the decrease of meat flavor caused
      by heat stress was relieved. 

PMID- 25049484
TI  - Re-evaluation of the Optimum Dietary Vitamin C Requirement in Juvenile Eel,
      Anguilla japonica by Using L-ascorbyl-2-monophosphate.
AB  - This study was conducted to re-evaluate the dietary vitamin C requirement in
      juvenile eel, Anguilla japonica by using L-ascorbyl-2-monophosphate (AMP) as the
      vitamin C source. Five semi-purified experimental diets were formulated to
      contain 0 (AMP0), 30 (AMP24), 60 (AMP52), 120 (AMP108) and 1,200 (AMP1137) mg AMP
      kg-1 diet on a dry matter basis. Casein and defatted fish meal were used as the
      main protein sources in the semi-purified experimental diets. After a 4-week
      conditioning period, fish initially averaging 15+/-0.3 g (mean+/-SD) were
      randomly distributed to each aquarium as triplicate groups of 20 fish each. One
      of five experimental diets was fed on a DM basis to fish in three randomly
      selected aquaria, at a rate of 3% of total body weight, twice a day. At the end
      of the feeding trial, weight gain (WG) and specific growth rate (SGR) for fish
      fed AMP52 and AMP108 were significantly higher than those recorded for fish fed
      the control diet (p<0.05). Similarly, feed efficiency (FE) and protein efficiency
      ratio (PER) for fish fed AMP52 were significantly higher than those for fish fed
      the control diet (p<0.05). Broken-line regression analysis on the basis of WG,
      SGR, FE and PER showed dietary vitamin C requirements of juvenile eel to be 41.1,
      41.2, 43.9 and 43.1 (mg kg(-1) diet), respectively. These results indicated that
      the dietary vitamin C requirement could range from 41.1 to 43.9 mg kg(-1) diet in
      juvenile eel when L-ascorbyl-2-monophosphate was used as the dietary source of
      vitamin C. 

PMID- 25049485
TI  - Energy and standardized ileal amino Acid digestibilities of chinese distillers
      dried grains, produced from different regions and grains fed to growing pigs.
AB  - Two experiments were conducted to determine the digestibility of crude protein
      (CP), amino acids and energy in three Chinese corn distillers dried grains with
      solubles (DDGS), one rice DDGS, one American corn DDGS and one American high
      protein distillers dried grains (HP-DDG). In Exp. 1, the apparent ileal
      digestibility (AID) and standardized ileal digestibility (SID) of CP and amino
      acids in the six samples were determined using cannulated barrows (initial BW:
      43.3+/-1.7 kg). In Exp. 2, the digestible energy (DE) and metabolizable energy
      (ME) content of these six samples were determined using crossbred barrows
      (initial BW: 46.0+/-2.5 kg). The results of the two experiments indicated that
      Chinese corn DDGS is generally similar to American DDGS in chemical composition,
      digestibility of amino acids, DE and ME. However, Chinese DDGS had a lower Lys
      concentration (0.50% vs. 0.74%) and SID Lys (52.3% vs. 57.0%, p<0.01). The DE and
      ME values in Chinese corn DDGS were 3,427 and 3,306 kcal/kg, respectively. Rice
      DDGS had a similar DE and ME (3,363 and 3,228 kcal/kg) but higher Lys
      concentration (0.64% vs. 0.50%) to corn DDGS, while the SID of Lys was quite low
      (61.8%, p<0.01). HP-DDG had high value of SID of Lys, DE and ME (79.8%, 3,899 and
      3,746 kcal/kg). In conclusion, except for a lower Lys concentrations and
      availability, the chemical composition, digestibility of amino acids, DE and ME
      values in Chinese corn DDGS are similar to American corn DDGS. Additionally, the
      rice DDGS had lower Lys content and digestible Lys values than that in corn DDGS.
      Thirdly, HP-DDG has higher levels of digestible amino acids and energy than DDGS.

PMID- 25049486
TI  - Isolation, screening and identification of Swine gut microbiota with ochratoxin a
      biodegradation ability.
AB  - The potential for ochratoxin A (OTA) degradation by swine intestinal microbiota
      was assessed in the current study. Intestinal content that was collected
      aseptically from swine was spiked with 100 ppb OTA and incubated for 6 and 12 h
      at 39 degrees C. An OTA assay was conducted using the incubated samples, and it
      was found that 20% of the OTA toxin was detoxified, indicating the presence of
      microbes capable of OTA degradation. Twenty-eight bacterial species were isolated
      anaerobically in M 98-5 media and 45 bacterial species were isolated using
      nutrient broth aerobically. Screening results showed that one anaerobic bacterial
      isolate, named MM11, detoxified more than 75% of OTA in liquid media.
      Furthermore, 1.0 ppm OTA was degraded completely after 24 h incubation on a solid
      'corn' substrate. The bacterium was identified by 16S rDNA sequencing as having
      97% sequence similarity with Eubacterium biforme. The isolation of an OTA
      degrading bacterium from the swine natural flora is of great importance for OTA
      biodegradation and may be a valuable potential source for OTA-degradation enzymes
      in industrial applications. 

PMID- 25049487
TI  - Rainfed areas and animal agriculture in Asia: the wanting agenda for transforming
      productivity growth and rural poverty.
AB  - The importance of rainfed areas and animal agriculture on productivity
      enhancement and food security for economic rural growth in Asia is discussed in
      the context of opportunities for increasing potential contribution from them. The
      extent of the rainfed area of about 223 million hectares and the biophysical
      attributes are described. They have been variously referred to inter alia as
      fragile, marginal, dry, waste, problem, threatened, range, less favoured, low
      potential lands, forests and woodlands, including lowlands and uplands. Of these,
      the terms less favoured areas (LFAs), and low or high potential are quite widely
      used. The LFAs are characterised by four key features: i) very variable
      biophysical elements, notably poor soil quality, rainfall, length of growing
      season and dry periods, ii) extreme poverty and very poor people who continuously
      face hunger and vulnerability, iii) presence of large populations of ruminant
      animals (buffaloes, cattle, goats and sheep), and iv) have had minimum
      development attention and an unfinished wanting agenda. The rainfed humid/sub
      humid areas found mainly in South East Asia (99 million ha), and arid/semi-arid
      tropical systems found in South Asia (116 million ha) are priority agro
      ecological zones (AEZs). In India for example, the ecosystem occupies 68% of the
      total cultivated area and supports 40% of the human and 65% of the livestock
      populations. The area also produces 4% of food requirements. The biophysical and
      typical household characteristics, agricultural diversification, patterns of
      mixed farming and cropping systems are also described. Concerning animals, their
      role and economic importance, relevance of ownership, nomadic movements, and more
      importantly their potential value as the entry point for the development of LFAs
      is discussed. Two examples of demonstrated success concern increasing buffalo
      production for milk and their expanded use in semi-arid AEZs in India, and the
      integration of cattle and goats with oil palm in Malaysia. Revitalised
      development of the LFAs is justified by the demand for agricultural land to meet
      human needs e.g. housing, recreation and industrialisation; use of arable land to
      expand crop production to ceiling levels; increasing and very high animal
      densities; increased urbanisation and pressure on the use of available land;
      growing environmental concerns of very intensive crop production e.g.
      acidification and salinisation with rice cultivation; and human health risks due
      to expanding peri-urban poultry and pig production. The strategies for promoting
      productivity growth will require concerted R and D on improved use of LFAs,
      application of systems perspectives for technology delivery, increased
      investments, a policy framework and improved farmer-researcher-extension
      linkages. These challenges and their resolution in rainfed areas can forcefully
      impact on increased productivity, improved livelihoods and human welfare, and
      environmental sustainability in the future. 

PMID- 25049488
TI  - Pork preference for consumers in china, Japan and South Korea.
AB  - Competition in global pork markets has increased as trade barriers have opened as
      a result of free trade agreements. Japanese prefer both loin and Boston butt,
      while Chinese prefer pork offal. Frozen pork has increased in terms of imports
      into China. Japanese consumers consider pork meat origin along with pork price
      when making purchase decisions. While the Chinese prefer a strong tasting pork
      product, South Korean consumers show very strong preferences to pork that is
      higher in fat. Therefore, South Korean consumers have a higher demand for pork
      belly and Boston butt. Consequently, the supply and demand of pork in Korea is
      hardly met, which means that importation of high fat parts is inevitable. In
      Korea there is lower preference toward low fat parts such as loin, picnic
      shoulder, and ham. During the economic depression in South Korea there have been
      observable changes in consumer preferences. There remains steep competition among
      the pork exporting countries in terms of gaining share in the international pork
      market. If specific consumer preferences would be considered carefully, there is
      the possibility to increase the amount of pork exported to these countries. 

PMID- 25049489
TI  - Comparison of Growth Performance of Antibiotic-free Yorkshire Crossbreds Sired by
      Berkshire, Large Black, and Tamworth Breeds Raised in Hoop Structures.
AB  - The objective of this study was to compare body weight, ADG, and feed:gain ratio
      of antibiotic-free pigs from Yorkshire dams and sired by Yorkshire (YY),
      Berkshire (BY), Large Black (LBY) or Tamworth (TY) boars. All the crossbred pigs
      in each of three trials were raised as one group from weaning to finishing in the
      same deep-bedded hoop, providing a comfortable environment for the animals which
      allowed rooting and other natural behaviors. Birth, weaning and litter weights
      were measured and recorded. From approximately 50 kg to market weight (125 kg),
      feed intake and body weights were recorded manually (body weight) or using a FIRE
      (Feed Intake Recording Equipment, Osborne Industries Inc. Osborne, Kansas) system
      with eight individual feeding stations. Feed intake data for 106 finishing pigs
      between 140 and 210 d of age and the resulting weights and feed conversion ratios
      were analyzed by breed type. Least square means for body weights (birth, weaning
      and to 240 d) were estimated with Proc Mixed in SAS 9.2 for fixed effects such as
      crossbreed and days of age within the sire breed. The differences within fixed
      effects were compared using least significant differences with DIFF option.
      Individual birth weights and weaning weights were influenced by sire breed
      (p<0.05). For birth weight, BY pigs were the lightest, TY and YY pigs were the
      heaviest but similar to each other and LBY pigs were intermediate. For weaning
      weights, BY and LBY pigs were heavier than TY and YY pigs. However, litter birth
      and weaning weights were not influenced by sire breed, and average daily gain was
      also not significantly different among breed types. Tamworth sired pigs had lower
      overall body weight gain, and feed conversion was lower in TY and YY groups than
      BY and LBY groups (p<0.05), however, number of observations was somewhat limited
      for feed conversion and for Tamworth pigs. Overall, no convincing differences
      among breed types were noted for this study, but growth performance in the
      outdoor environment was satisfactory. 

PMID- 25049490
TI  - Characterization of insertional variation of porcine endogenous retroviruses in
      six different pig breeds.
AB  - Pigs may need to be exploited as xenotransplantation donors due to the shortage
      of human organs, tissues and cells. Porcine endogenous retroviruses (PERVs) are a
      significant obstacle to xenotransplantation because they can infect human cells
      in vitro and have the potential for transmission of unexpected pathogens to
      humans. In this research, 101 pigs, including four commercial breeds (23
      Berkshire, 13 Duroc, 22 Landrace and 14 Yorkshire pigs), one native breed (19
      Korean native pigs) and one miniature breed (10 NIH miniature pigs) were used to
      investigate insertional variations for 11 PERV loci (three PERV-A, six PERV-B and
      two PERV-C). Over 60% of the pigs harbored one PERV-A (907F8) integration and
      five PERV-B (B3-3G, B3-7G, 742H1, 1155D9 and 465D1) integrations. However, two
      PERV-A loci (A1-6C and 1347C1) and one PERV-B locus (B3-7F) were absent in Duroc
      pigs. Moreover, two PERV-C loci (C2-6C and C4-2G) only existed in Korean native
      pigs and NIH miniature pigs. The results suggest that PERV insertional variations
      differ among pig breeds as well as among individuals within a breed. Also, the
      results presented here can be used for the selection of animals that do not have
      specific PERV integration for xenotransplantation research. 

PMID- 25049491
TI  - Effect of cassava hay and rice bran oil supplementation on rumen fermentation,
      milk yield and milk composition in lactating dairy cows.
AB  - Four crossbred (75% Holstein Friesian) lactating dairy cows, with an average live
      weight of 418+/-5 kg and 36+/-10 d in milk were randomly assigned according to a
      2*2 factorial arrangement in a 4*4 Latin square design to evaluate the effects of
      cassava hay (CH) and rice bran oil (RBO) on feed intake, nutrient digestibility,
      ruminal fermentation, milk yield, and milk composition. Factor A was non
      supplementation or supplementation with CH in the concentrate. Factor B was
      supplementation with RBO at 0% or 4% in the concentrate mixture. The four dietary
      treatments were (T1) control (Concentrate with non-CH plus 0% RBO; C), (T2)
      Concentrate with CH plus 0% RBO (CH), (T3) Concentrate with non-CH plus 4% RBO
      (RBO), and (T4) Concentrate with CH plus 4% RBO (CHRBO). The cows were offered
      concentrate, at a ratio of concentrate to milk production of 1:2, and urea-lime
      treated rice straw was fed ad libitum. Urea-lime treated rice straw involved 2.5
      g urea and 2.5 g Ca(OH)2 (purchased as hydrated lime) in 100 ml water, the
      relevant volume of solution was sprayed onto a 100 g air-dry (91% DM) straw, and
      then covering the stack with a plastic sheet for a minimum of 10 d before feeding
      directly to animals. The CH based concentrate resulted in significantly higher
      roughage intake and total DM intake expressed as a percentage of BW (p<0.05).
      Ruminal pH, NH3-N, BUN and total VFA did not differ among treatments, while RBO
      supplementation increased propionate, but decreased acetate concentration
      (p<0.05). Furthermore, the population of total ruminal bacteria was significantly
      lower on the RBO diet (p<0.05). In contrast, the total ruminal bacteria and
      cellulolytic bacteria on the CH diet were higher than on the other treatments.
      Supplementation with CH increased (p<0.05) F. succinogens and R. flavefaciens
      populations, whereas the populations of B. fibrisolvens and M. elsdenii were
      increased on the RBO diet. In addition, supplementation with CH and RBO had no
      effect on milk production and composition in dairy cows, while fatty acid
      composition of milk was influenced by RBO supplementation, and resulted in
      significantly lower (p<0.05) concentrations of both short-chain and medium-chain
      FA, and increased (p<0.05) the proportion of long-chain FA in milk fat, as well
      as significantly increased cis-9, trans-11 CLA and total CLA. In conclusion, RBO
      or CH exhibited specific effects on DM, rumen fermentation, microbial population,
      milk yield and composition in lactating dairy cows, which were not interactions
      between CH and RBO in the diets. Feeding lactating dairy cows with RBO could
      improve fatty acid in milk fat by increasing cis-9, trans-11 CLA. 

PMID- 25049492
TI  - Effects of maturity stages on the nutritive composition and silage quality of
      whole crop wheat.
AB  - The changes in yields and nutritive composition of whole crop wheat (Triticum
      aestivum L.) during maturation and effects of maturity stage and lactic acid
      bacteria (LAB) inoculants on the fermentation quality and aerobic stability were
      investigated under laboratory conditions. Whole crop wheat harvested at three
      maturation stages: flowering stage, milk stage and dough stage. Two strains of
      LAB (Lactobacillus plantarum: LAB1, Lactobacillus parafarraqinis: LAB2) were
      inoculated for wheat ensiling at 1.0*10(5) colony forming units per gram of fresh
      forage. The results indicated that wheat had higher dry matter yields at the milk
      and dough stages. The highest water-soluble carbohydrates content, crude protein
      yields and relative feed value of wheat were obtained at the milk stage, while
      contents of crude fiber, neutral detergent fiber and acid detergent fiber were
      the lowest, compared to the flowering and dough stages. Lactic acid contents of
      wheat silage significantly decreased with maturity. Inoculating homofermentative
      LAB1 markedly reduced pH values and ammonia-nitrogen (NH3-N) content (p<0.05) of
      silages at three maturity stages compared with their corresponding controls.
      Inoculating heterofermentative LAB2 did not significantly influence pH values,
      whereas it notably lowered lactic acid and NH3-N content (p<0.05) and effectively
      improved the aerobic stability of silages. In conclusion, considering both yields
      and nutritive value, whole crop wheat as forage should be harvested at the milk
      stage. Inoculating LAB1 improved the fermentation quality, while inoculating LAB2
      enhanced the aerobic stability of wheat silages at different maturity stages. 

PMID- 25049493
TI  - Effects of Defaunation on Fermentation Characteristics and Methane Production by
      Rumen Microbes In vitro When Incubated with Starchy Feed Sources.
AB  - An in vitro experiment was conducted to examine the effects of defaunation
      (removal of protozoa) on ruminal fermentation characteristics, CH4 production and
      degradation by rumen microbes when incubated with cereal grains (corn, wheat and
      rye). Sodium lauryl sulfate as a defaunation reagent was added into the culture
      solution at a concentration of 0.000375 g/ml, and incubated anaerobically for up
      to 12 h at 39 degrees C. Following defaunation, live protozoa in the culture
      solution were rarely observed by microscopic examination. A difference in pH was
      found among grains regardless of defaunation at all incubation times (p<0.01 to
      0.001). Defaunation significantly decreased pH at 12 h (p<0.05) when rumen fluid
      was incubated with grains. Ammonia-N concentration was increased by defaunation
      for all grains at 6 h (p<0.05) and 12 h (p<0.05) incubation times. Total VFA
      concentration was increased by defaunation at 6 h (p<0.05) and 12 h (p<0.01) for
      all grains. Meanwhile, defaunation decreased acetate and butyrate proportions at
      6 h (p<0.05, p<0.01) and 12 h (p<0.01, p<0.001), but increased the propionate
      proportion at 3 h, 6 h and 12 h incubation (p<0.01 to 0.001) for all grains.
      Defaunation increased in vitro effective degradability of DM (p<0.05). Production
      of total gas and CO2 was decreased by defaunation for all grains at 1 h (p<0.05,
      p<0.05) and then increased at 6 h (p<0.05, p<0.05) and 12 h (p<0.05, p<0.05). CH4
      production was higher from faunation than from defaunation at all incubation
      times (p<0.05). 

PMID- 25049494
TI  - Phenolic Composition, Fermentation Profile, Protozoa Population and Methane
      Production from Sheanut (Butryospermum Parkii) Byproducts In vitro.
AB  - Sheanut cake (SNC), expeller (SNE) and solvent extractions (SNSE) samples were
      evaluated to determine their suitability in animal feeding. The CP content was
      highest in SNSE (16.2%) followed by SNE (14.7%) and SNC (11.6%). However,
      metabolizable energy (ME, MJ/kg) was maximum in SNC (8.2) followed by SNE (7.9)
      and SNSE (7.0). The tannin phenol content was about 7.0 per cent and mostly in
      the form of hydrolyzable tannin (HT), whereas condensed tannin (CT) was less than
      one per cent. The in vitro gas production profiles indicated similar y max
      (maximum potential of gas production) among the 3 by-products. However, the rate
      of degradation (k) was maximum in SNC followed by SNE and SNSE. The t(1/2) (time
      taken for reaching half asymptote) was lowest in SNC (14.4 h) followed by SNE
      (18.7 h) and SNSE (21.9 h). The increment in the in vitro gas volume (ml/200 mg
      DM) with PEG (polyethylene glycol)-6000 (as a tannin binder) addition was 12.0 in
      SNC, 9.6 in SNE and 11.0 in SNSE, respectively. The highest ratio of CH4 (ml)
      reduction per ml of the total gas, an indicator of the potential of tannin, was
      recorded in SNE (0.482) followed by SNC (0.301) and SNSE (0.261). There was
      significant (p<0.05) reduction in entodinia population and total protozoa
      population. Differential protozoa counts revealed that Entodinia populations
      increased to a greater extent than Holotricha when PEG was added. This is the
      first report on the antimethanogenic property of sheanut byproducts. It could be
      concluded that all the three forms of SN byproducts are medium source of protein
      and energy for ruminants. There is a great potential for SN by-products to be
      incorporated in ruminant feeding not only as a source of energy and protein, but
      also to protect the protein from rumen degradation and suppress enteric
      methanogenesis. 

PMID- 25049495
TI  - Chemical Composition, In vitro Gas Production, Ruminal Fermentation and
      Degradation Patterns of Diets by Grazing Steers in Native Range of North Mexico.
AB  - The objective of the study was to quantify annual and seasonal differences in the
      chemical composition, in vitro gas production, in situ degradability and ruminal
      fermentation of grazing steers' diets. Diet samples were collected with four
      esophageal cannulated steers (350+/-3 kg BW); and four ruminally cannulated
      heifers (342+/-1.5 kg BW) were used to study the dry matter degradation and
      fermentation in rumen. Data were analyzed with repeated measurements split plot
      design. The crude protein, in vitro dry matter digestibility and metabolizable
      energy were higher during the first year of trial and in the summer (p<0.01). The
      values of calcium, phosphorus, magnesium, zinc and copper were higher in summer
      (p<0.05). The gas produced by the soluble and insoluble fractions, as well as the
      constant rate of gas production were greater in summer and fall (p<0.01). The
      ammonia nitrogen (NH3N) and total volatile fatty acids concentrations in rumen,
      the soluble and degradable fractions, the constant rate of degradation and the
      effective degradability of DM and NDF were affected by year (p<0.05) and season
      (p<0.01). Our study provides new and useful knowledge for the formulation of
      protein, energetic and mineral supplements that grazing cattle need to improve
      their productive and reproductive performance. 

PMID- 25049496
TI  - Effects of tropical high tannin non legume and low tannin legume browse mixtures
      on fermentation parameters and methanogenesis using gas production technique.
AB  - In vitro experiments were conducted to evaluate the suitability of several
      mixtures of high tanniniferous non legumes with low tanniniferous legumes on in
      vitro gas production (IVGP), dry matter degradation, Ammonia-N, methane
      production and microbial population. Eight treatments were examined in a
      randomized complete block design using four non-legumes and two legumes (Carallia
      integerrima*Leucaena leucocephala (LL) (Trt 1), C. integerrima*Gliricidia sepium
      (GS) (Trt 2), Aporosa lindeliyana*LL (Trt 3), A. lindeliyana*GS (Trt 4), Ceiba
      perntandra*LL (Trt 5), C. perntandra*GS (Trt 6), Artocarpus heterophyllus*LL (Trt
      7), A. heterophyllus*GS (Trt 8). The condensed tannin (CT) content of non legumes
      ranged from 6.2% (Carallia integerrima) to 4.9% (Ceiba perntandra) while the CT
      of legumes were 1.58% (Leucaena leucocephala) and 0.78% (Gliricidia sepium).
      Forage mixtures contained more than 14% of crude protein (CP) while the CT
      content ranged from 2.8% to 4.0% respectively. Differences (p<0.05) were observed
      in in vitro gas production (IGVP) within treatments over a 48 h period dominated
      by C. perntandra*G. sepium (Trt 6). The net gas production (p<0.05) was also high
      with Trt6 followed by A. heterophyllus*L. leucocephala (Trt 7) and A.
      heterophyllus*G. sepium (Trt 8). Highest (p>0.05) NH3-N (ml/200 mg DM) production
      was observed with the A. heterophyllus*G. sepium (Trt 8) mixture which may be
      attributed with it's highest CP content. The correlation between IVGP and CT was
      0.675 while IVGP and CP was 0.610. In vitro dry matter degradation (IVDMD) was
      highest in Trt 8 as well. Methane production ranged from 2.57 to 4.79 (ml/200 mg
      DM) to be synonimous with IVGP. A higher bacteria population (p<0.05) was found
      in C. perntandra*G. sepium (Trt 6) followed by Artocarpus heterophyllus+G. sepium
      (Trt 8) and the same trend was observed with the protozoa population as well. The
      results show that supplementing high tannin non leguminous forages by incremental
      substitution of legume forage increased gas production parameters, NH3-N, IVDMD
      and microbial population in the fermentation liquid. Methane production was not
      significantly affected by the presence of CT or different levels of CP in forage
      mixtures. Among non legumes, Ceiba perntandra and Artocarpus heterophyllus
      performed better in mixture with L. leucocephala and G. sepium. 

PMID- 25049497
TI  - Transfer of orally administered terpenes in goat milk and cheese.
AB  - The objective of the present study was to investigate the relationships between
      terpenes' intake and their presence in animal tissues (blood and milk) as well as
      in the final product (cheese). Eight dairy goats were divided in two balanced
      groups, representing control (C) and treatment (T) group. In T group oral
      administration of a mixture of terpenes (alpha-pinene, limonene and beta
      caryophyllene) was applied over a period of 18 d. Cheese was produced, from C and
      T groups separately, on three time points, twice during the period of terpenes'
      oral administration and once after the end of experiment. Terpenes were
      identified in blood by extraction using petroleum ether and in milk and cheese by
      the use of solid phase micro-extraction (SPME) method, followed by GC-MS
      analysis. Chemical properties of the milk and the produced cheeses were analyzed
      and found not differing between the two groups. Limonene and alpha-pinene were
      found in all blood and milk samples of the T group after a lag-phase of 3 d,
      while beta-caryophyllene was determined only in few milk samples. Moreover, none
      of the terpenes were traced in blood and milk of C animals. In cheese, terpenes'
      concentrations presented a more complicated pattern implying that terpenes may
      not be reliable feed tracers. We concluded that monoterpenes can be regarded as
      potential feed tracers for authentification of goat milk, but further research is
      required on factors affecting their transfer. 

PMID- 25049498
TI  - Effects of Dietary Garlic Extracts on Whole Body Amino Acid and Fatty Acid
      Composition, Muscle Free Amino Acid Profiles and Blood Plasma Changes in Juvenile
      Sterlet Sturgeon, Acipenser ruthenus.
AB  - A series of studies were carried out to investigate the supplemental effects of
      dietary garlic extracts (GE) on whole body amino acids, whole body and muscle
      free amino acids, fatty acid composition and blood plasma changes in 6 month old
      juvenile sterlet sturgeon (Acipenser ruthenus). In the first experiment, fish
      with an average body weight of 59.6 g were randomly allotted to each of 10 tanks
      (two groups of five replicates, 20 fish/tank) and fed diets with (0.5%) or
      without (control) GE respectively, at the level of 2% of fish body weight per day
      for 5 wks. Whole body amino acid composition between the GE and control groups
      were not different (p>0.05). Among free amino acids in muscle, L-glutamic acid, L
      alanine, L-valine, L-leucine and L-phenylalanine were significantly (p<0.05)
      higher in GE than in control. However, total whole body free amino acids were
      significantly lower in GE than in control (p<0.05). GE group showed higher EPA
      (C22:6n3) and DHA (C22:5n3) in their whole body than the other group (p<0.05). In
      the second experiment, the effects of dietary garlic extracts on blood plasma
      changes were investigated using 6 month old juvenile sterlet sturgeon averaging
      56.5 g. Fish were randomly allotted to each of 2 tanks (300 fish/tank) and fed
      diets with (0.5%) or without (control) GE respectively, at the rate of 2% of body
      weight per day for 23 d. At the end of the feeding trial, blood was taken from
      the tail vein (n = 5, per group) at 1, 12, and 24 h after feeding, respectively.
      Blood plasma glucose, insulin and the other serological characteristics were also
      measured to assess postprandial status of the fish. Plasma glucose concentrations
      (mg/dl) between two groups (GE vs control) were significantly (p< 0.05) different
      at 1 (50.8 vs 62.4) and 24 h (57.6 vs 73.6) after feeding, respectively, while no
      significant difference (p>0.05) were noticed at 12 h (74.6 vs 73.0). Plasma
      insulin concentrations (MUIU/ml) between the two groups were significantly
      (p<0.05) different at 1 (10.56 vs 5.06) and 24 h (32.56 vs 2.96) after feeding.
      The present results suggested that dietary garlic extracts could increase dietary
      glucose utilization through the insulin secretion, which result in improved fish
      body quality and feed utilization by juvenile sterlet sturgeon. 

PMID- 25049499
TI  - Evaluation of energy digestibility and prediction of digestible and metabolizable
      energy from chemical composition of different cottonseed meal sources fed to
      growing pigs.
AB  - The present experiment was conducted to determine the digestible energy (DE),
      metabolizable energy (ME) content, and the apparent total tract digestibility
      (ATTD) of energy in growing pigs fed diets containing one of ten cottonseed meals
      (CSM) collected from different provinces of China and to develop in vitro
      prediction equations for DE and ME content from chemical composition of the CSM
      samples. Twelve growing barrows with an initial body weight of 35.2+/-1.7 kg were
      allotted to two 6*6 Latin square designs, with six barrows and six periods and
      six diets for each. A corn-dehulled soybean meal diet was used as the basal diet,
      and the other ten diets were formulated with corn, dehulled soybean meal and
      19.20% CSM. The DE, ME and ATTD of gross energy among different CSM sources
      varied largely and ranged from 1,856 to 2,730 kcal/kg dry matter (DM), 1,778 to
      2,534 kcal/kg DM, and 42.08 to 60.47%, respectively. Several chemical parameters
      were identified to predict the DE and ME values of CSM, and the accuracy of
      prediction models were also tested. The best fit equations were: DE, kcal/kg DM =
      670.14+31.12 CP+659.15 EE with R(2) = 0.82, RSD = 172.02, p<0.05; and ME, kcal/kg
      DM = 843.98+25.03 CP+673.97 EE with R(2) = 0.84, RSD = 144.79, p<0.05. These
      results indicate that DE, ME values and ATTD of gross energy varied substantially
      among different CSM sources, and that some prediction equations can be applied to
      predict DE and ME in CSM with an acceptable accuracy. 

PMID- 25049500
TI  - Evaluation of Houttuynia cordata and Taraxacum officinale on Growth Performance,
      Nutrient Digestibility, Blood Characteristics, and Fecal Microbial Shedding in
      Diet for Weaning Pigs.
AB  - A total of 144 pigs ((Landrace*Yorkshire)*Duroc] with an average initial BW of
      8.45+/-0.57 kg were used in a 5-wk growth trial. Pigs were randomly allocated to
      4 treatments with 9 replications per pen in a randomized complex block design.
      Dietary treatments included: i) CON (basal diet), ii) ANT (CON+tylosin 1 g/kg),
      iii) H1 (CON+H. cordata 1 g/kg) and iv) T1 (CON+T. officinale 1 g/kg). In this
      study, pigs fed the ANT and T1 treatment had a higher (p<0.05) average daily gain
      (ADG) and gain:feed (G:F) ratio than those fed CON and H1 treatment. Dietary ANT
      and T1 treatment led to a higher energy digestibility than the CON group. No
      difference (p>0.05) was observed on the growth performance and apparent total
      tract digestibility with H1 supplementation compared with the CON treatment. The
      inclusion of ANT treatment led to a higher (p<0.05) lymphocyte concentration
      compared with the CON treatment. Dietary supplementation of herbs did not affect
      (p>0.05) the blood characteristics (white blood cell (WBC), red blood cell (RBC),
      IgG, lymphocyte). No difference was observed on (p<0.05) fecal microbial shedding
      (E. coli and lactobacillus) between ANT and CON groups. Treatments H1 and T1
      reduced the fecal E. coli concentration compared with the CON treatment, whereas
      the fecal lactobacillus concentration was not affected by the herb
      supplementation (p>0.05). In conclusion, the inclusion of T. officinale (1 g/kg)
      increased growth performance, feed efficiency, energy digestibility similarly to
      the antibiotic treatment. Dietary supplementation of T. officinale and H. cordata
      (1 g/kg) reduced the fecal E. coli concentration in weaning pigs. 

PMID- 25049501
TI  - Effects of alfalfa meal on growth performance and gastrointestinal tract
      development of growing ducks.
AB  - A study was conducted to evaluate effects of alfalfa meal on growth performance
      and gastrointestinal tract development of growing layer ducks to provide evidence
      for application of alfalfa meal in the duck industry. Two hundred and fifty-six
      healthy Shaoxing 7-wk old growing layer ducks were selected and randomly
      allocated to 1 of 4 dietary treatments based on corn and soybean meal and
      containing 0, 3, 6, and 9% of alfalfa meal for 8 wks. Each treatment consisted of
      4 replicates of 16 ducks each. Briefly, birds were raised in separate
      compartments, and each compartment consisted of three parts: indoor floor house,
      adjacent open area and a connecting water area. The results showed: i) Growing
      ducks fed alfalfa meal diet were not significantly different in average daily
      gain, feed intake and gain-to-feed ratio from those fed no alfalfa diet (p>0.05).
      ii) Alfalfa meal increased the ratio crop, gizzard to live weight, caecum to live
      weight, the caecum index of growing ducks (p<0.05). iii) Villus height in
      duodenum and jejunum of growing ducks increased significantly with the increase
      of alfalfa meal levels (p<0.05). Crypt depth in duodenum and jejunum of growing
      ducks decreased significantly with the increase of alfalfa meal levels (p<0.05).
      This experiment showed that feeding of alfalfa meal to growing layer ducks could
      improve gastrointestinal tract growth and small intestinal morphology without
      effect on performance. This experiment provides evidence that alfalfa meal is a
      very valuable feedstuff for growing layer ducks. 

PMID- 25049502
TI  - Effect of bacteriophage supplementation on the growth performance, nutrient
      digestibility, blood characteristics, and fecal microbial shedding in growing
      pigs.
AB  - A total of 144 ((Duroc*Yorkshire)*Landrace)) pigs with an average initial BW of
      28.85+/-0.63 kg were used in this 6-wk growth trial. Pigs were randomly allotted
      to 1 of 4 treatments in a completely random block design. Each dietary treatment
      consisted of 9 replicate pens, with 4 pigs per replicate. Dietary treatments
      included: i) NC (basal diet), ii) PC (NC+apramycin 0.5 g/kg), iii) BPT1
      (NC+bacteriophage 0.25 g/kg) and iv) BPT2 (NC+bacteriophage 0.5 g/kg). The
      inclusion of antibiotics and bacteriophages did not affect the (p>0.05) ADG, ADFI
      and G:F compared with the basal diet. Dietary antibiotics and bacteriophages
      supplementation led to a higher (p<0.05) DM digestibility than the NC treatment.
      Pigs fed the bacteriophage supplemented diet increased (p<0.05) the N
      digestibility compared with those fed NC treatment. Supplementation of
      antibiotics led to a higher (p<0.05) energy digestibility than the NC treatment.
      No difference (p>0.05) was observed in the RBC, WBC, lymphocyte concentration and
      fecal moisture among treatments. Pigs fed PC and BPT2 treatments reduced (p<0.05)
      the E. coli concentration compared with those fed NC treatment. The inclusion of
      BPT2 treatment led to a higher (p<0.05) lactobacillus concentration compared with
      NC and PC treatment. Dietary antibiotic and bacteriophage supplementation reduced
      (p<0.05) the Salmonella concentration compared with NC treatment. In conclusion,
      our study suggested that bacteriophage at the level of 0.5 g/kg could be used as
      an antibiotics alternative for growing pigs. 

PMID- 25049503
TI  - Different phosphate transport in the duodenum and jejunum of chicken response to
      dietary phosphate adaptation.
AB  - Intestinal phosphate (Pi) absorption across the apical membrane of small
      intestinal epithelial cells is mainly mediated by the type IIb Na-coupled
      phosphate co-transporter (NaPi-IIb), but its expression and regulation in the
      chicken remain unclear. In the present study, we investigated the mRNA and
      protein levels of NaPi-IIb in three regions of chicken small intestine, and
      related their expression levels to the rate of net phosphate absorption. Our
      results showed that maximal phosphate absorption occurs in the jejunum, however
      the highest expression levels of NaPi-IIb mRNA and protein occurs in the
      duodenum. In response to a low-Pi diet (TP 0.2%), there is an adaptive response
      restricted to the duodenum, with increased brush border membrane (BBM) Na-Pi
      transport activity and NaPi-IIb protein and mRNA abundance. However, when
      switched from a low- (TP 0.2%) to a normal diet (TP 0.6%) for 4 h, there is an
      increase in BBM NaPi-IIb protein abundance in the jejunum, but no changes in BBM
      NaPi-IIb mRNA. Therefore, our study indicates that Na-Pi transport activity and
      NaPi-IIb protein expression are differentially regulated in the duodenum vs the
      jejunum in the chicken. 

PMID- 25049504
TI  - Degradation of Phytate Pentamagnesium Salt by Bacillus sp. T4 Phytase as a
      Potential Eco-friendly Feed Additive.
AB  - A bacterial isolate derived from soil samples near a cattle farm was found to
      display extracellular phytase activity. Based on 16S rRNA sequence analysis, the
      strain was named Bacillus sp. T4. The optimum temperature for the phytase
      activity toward magnesium phytate (Mg-InsP6) was 40 degrees C without 5 mM Ca(2+)
      and 50 degrees C with 5 mM Ca(2+). T4 phytase had a characteristic bi-hump two pH
      optima of 6.0 to 6.5 and 7.4 for Mg-InsP6. The enzyme showed higher specificity
      for Mg-InsP6 than sodium phytate (Na-InsP6). Its activity was fairly inhibited by
      EDTA, Cu(2+), Mn(2+), Co(2+), Ba(2+) and Zn(2+). T4 phytase may have great
      potential for use as an eco-friendly feed additive to enhance the nutritive
      quality of phytate and reduce phosphorus pollution. 

PMID- 25049505
TI  - Porcine Knock-in Fibroblasts Expressing hDAF on alpha-1,3-Galactosyltransferase
      (GGTA1) Gene Locus.
AB  - The Galactose-alpha1,3-galactose (alpha1,3Gal) epitope is responsible for
      hyperacute rejection in pig-to-human xenotransplantation. Human decay
      accelerating factor (hDAF) is a cell surface regulatory protein that serves as a
      complement inhibitor to protect self cells from complement attack. The generation
      of alpha1,3-galactosyltransferase (GGTA1) knock-out pigs expressing DAF is a
      necessary step for their use as organ donors for humans. In this study, we
      established GGTA1 knock-out cell lines expressing DAF from pig ear fibroblasts
      for somatic cell nuclear transfer. hDAF expression was detected in hDAF knock-in
      heterozygous cells, but not in normal pig cells. Expression of the GGTA1 gene was
      lower in the knock-in heterozygous cell line compared to the normal pig cell.
      Knock-in heterozygous cells afforded more effective protection against
      cytotoxicity with human serum than with GGTA1 knock-out heterozygous and control
      cells. These cell lines may be used in the production of GGTA1 knock-out and DAF
      expression pigs for xenotransplantation. 

PMID- 25049507
TI  - Effect of amaranthus pigments on quality characteristics of pork sausages.
AB  - The objective of this investigation was to evaluate the possibility of
      substituting Amaranthus pigments for nitrates in the of manufacture pork sausage.
      Five treatments of pork sausages (5% fat) with two levels of sodium nitrite (0
      and 0.015%), or three levels (0.1%, 0.2% and 0.3%) of pigments extracted from red
      Amaranthus were produced. The addition of Amaranthus pigments resulted in the
      significant increase of a* values, sensory color, flavor and overall acceptance
      scores, but the significant reduction of b* values, TBA values and VBN values
      (p<0.05). Based mainly on the results of overall acceptance during 29 d storage,
      it could be concluded that Amaranthus pigments showed a potential as nitrite
      alternative for pork sausage manufacture. 

PMID- 25049508
TI  - Animal welfare in different human cultures, traditions and religious faiths.
AB  - Animal welfare has become a growing concern affecting acceptability of
      agricultural systems in many countries around the world. An earlier Judeo
      Christian interpretation of the Bible (1982) that dominion over animals meant
      that any degree of exploitation was acceptable has changed for most people to
      mean that each person has responsibility for animal welfare. This view was
      evident in some ancient Greek writings and has parallels in Islamic teaching. A
      minority view of Christians, which is a widespread view of Jains, Buddhists and
      many Hindus, is that animals should not be used by humans as food or for other
      purposes. The commonest philosophical positions now, concerning how animals
      should be treated, are a blend of deontological and utilitarian approaches. Most
      people think that extremes of poor welfare in animals are unacceptable and that
      those who keep animals should strive for good welfare. Hence animal welfare
      science, which allows the evaluation of welfare, has developed rapidly. 

PMID- 25049506
TI  - Paradigm of Time-sequence Development of the Intestine of Suckling Piglets with
      Microarray.
AB  - The interaction of the genes involved in intestinal development is the molecular
      basis of the regulatory mechanisms of intestinal development. The objective of
      this study was to identify the significant pathways and key genes that regulate
      intestinal development in Landrace piglets, and elucidate their rules of
      operation. The differential expression of genes related to intestinal development
      during suckling time was investigated using a porcine genome array. Time sequence
      profiles were analyzed for the differentially expressed genes to obtain
      significant expression profiles. Subsequently, the most significant profiles were
      assayed using Gene Ontology categories, pathway analysis, network analysis, and
      analysis of gene co-expression to unveil the main biological processes, the
      significant pathways, and the effective genes, respectively. In addition,
      quantitative real-time PCR was carried out to verify the reliability of the
      results of the analysis of the array. The results showed that more than 8000
      differential expression transcripts were identified using microarray technology.
      Among the 30 significant obtained model profiles, profiles 66 and 13 were the
      most significant. Analysis of profiles 66 and 13 indicated that they were mainly
      involved in immunity, metabolism, and cell division or proliferation. Among the
      most effective genes in these two profiles, CN161469, which is similar to
      methylcrotonoyl-Coenzyme A carboxylase 2 (beta), and U89949.1, which encodes a
      folate binding protein, had a crucial influence on the co-expression network. 

PMID- 25049509
TI  - Detection of quantitative trait Loci affecting fat deposition traits in pigs.
AB  - Quantitative trait loci (QTL) associated with fat deposition traits in pigs are
      important gene positions in a chromosome that influence meat quality of pork. For
      QTL study, a three generation resource population was constructed from a cross
      between Korean native boars and Landrace sows. A total of 240 F2 animals from
      intercross of F1 were produced. 80 microsatellite markers covering chromosomes 1
      to 10 were selected to genotype the resource population. Intervals between
      adjacent markers were approximately 19 cM. Linkage analysis was performed using
      CRIMAP software version 2.4 with a FIXED option to obtain the map distances. For
      QTL analysis, the public web-based software, QTL express
      (http://www.qtl.cap.ed.ac.uk) was used. Two significant and two suggestive QTL
      were identified on SSC 6, 7, and 8 as affecting body fat and IMF traits. For QTL
      affecting IMF, the most significant association was detected between marker sw71
      and sw1881 on SSC 6, and a suggestive QTL was identified between sw268 and sw205
      on SSC8. These QTL accounted for 26.58% and 12.31% of the phenotypic variance,
      respectively. A significant QTL affecting IMF was detected at position 105 cM
      between markers sw71 and sw1881 on SSC 6. 

PMID- 25049510
TI  - Empirical Statistical Power for Testing Multilocus Genotypic Effects under
      Unbalanced Designs Using a Gibbs Sampler.
AB  - Epistasis that may explain a large portion of the phenotypic variation for
      complex economic traits of animals has been ignored in many genetic association
      studies. A Baysian method was introduced to draw inferences about multilocus
      genotypic effects based on their marginal posterior distributions by a Gibbs
      sampler. A simulation study was conducted to provide statistical powers under
      various unbalanced designs by using this method. Data were simulated by combined
      designs of number of loci, within genotype variance, and sample size in
      unbalanced designs with or without null combined genotype cells. Mean empirical
      statistical power was estimated for testing posterior mean estimate of combined
      genotype effect. A practical example for obtaining empirical statistical power
      estimates with a given sample size was provided under unbalanced designs. The
      empirical statistical powers would be useful for determining an optimal design
      when interactive associations of multiple loci with complex phenotypes were
      examined. 

PMID- 25049511
TI  - DNA Polymorphism of Insulin-like Growth Factor-binding Protein-3 Gene and Its
      Association with Cashmere Traits in Cashmere Goats.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) gene is important for
      regulation of growth and development in mammals. The present investigation was
      carried out to study DNA polymorphism by PCR-RFLP of IGFBP-3 gene and its effect
      on fibre traits of Chinese Inner Mongolian cashmere goats. The fibre traits data
      investigated were cashmere fibre diameter, combed cashmere weight, cashmere fibre
      length and guard hair length. Four hundred and forty-four animals were used to
      detect polymorphisms in the hircine IGFBP-3 gene. A 316-bp fragment of the IGFBP
      3 gene in exon 2 was amplified and digested with HaeIII restriction enzyme. Three
      patterns of restriction fragments were observed in the populations. The frequency
      of AA, AB and BB genotypes was 0.58, 0.33 and 0.09 respectively. The allelic
      frequency of the A and B allele was 0.75 and 0.25 respectively. Nucleotide
      sequencing revealed a C>G transition in the exon 2 region of the IGFBP-3 gene
      resulting in R158G change which caused the polymorphism. Least squares analysis
      revealed a significant effect of genotypes on cashmere weight (p<0.0001),
      cashmere fibre length (p<0.001) and hair length (p<0.05) of the animals. The
      effect of genotypes on cashmere fibre diameter was not statistically significant
      (p>0.05). The animals of AB and BB genotypes showed higher cashmere weight,
      cashmere fibre length and hair length than the animals possessing AA genotype.
      These results suggested that polymorphisms in the hircine IGFBP-3 gene might be a
      potential molecular marker for cashmere weight in cashmere goats. 

PMID- 25049512
TI  - Evaluation of BTA1 and BTA5 QTL Regions for Growth and Carcass Traits in American
      and Korean Cattle.
AB  - Previously identified QTL regions on BTA1 and BTA5 were investigated to validate
      the QTL regions and to identify candidate genes for growth and carcass traits in
      commercial cattle populations from the USA and Korea. Initially, a total of 8
      polymorphic microsatellite (MS) markers in the BTA1 and 5 QTL regions were used
      for Chi-square tests to compare the frequencies of individual alleles between
      high and low phenotypic groups for the US (Michigan Cattleman's
      Association/Michigan State University; MCA/MSU) cattle. For a subsequent study,
      24 candidate genes containing missense mutations and located within the QTL
      regions based on bovine genome sequence data were analyzed for genotyping in the
      two commercial cattle populations. Re-sequencing analyses confirmed 18 public
      missense SNPs and identified 9 new SNPs. Seventeen of these SNPs were used for
      genotyping of the MCA/MSU cattle (n = 98) and Korean native cattle (n = 323). On
      BTA1, UPK1B, HRG, and MAGEF1 polymorphisms residing between BM1312 and BMS4048
      were significantly associated with growth and carcass traits in one or both of
      the MCA/MSU and Korean populations. On BTA5, ABCD2, IL22 and SNRPF polymorphisms
      residing between BL4 and BR2936 were associated with marbling and backfat traits
      in one or both of the MCA/MSU and Korean cattle populations. These results
      suggested that BTA 1 and 5 QTL regions may be segregating in both Korean Hanwoo
      and USA commercial cattle populations and DNA markers tested in this study may
      contribute to the identification of positional candidate genes for marker
      assisted selection programs. 

PMID- 25049513
TI  - A Whole Genome Association Study on Meat Quality Traits Using High Density SNP
      Chips in a Cross between Korean Native Pig and Landrace.
AB  - A whole genome association (WGA) study was performed to detect significant
      polymorphisms for meat quality traits in an F2 cross population (N = 478) that
      were generated with Korean native pig sires and Landrace dams in National
      Livestock Research Institute, Songwhan, Korea. The animals were genotyped using
      Illumina porcine 60k SNP beadchips, in which a set of 46,865 SNPs were available
      for the WGA analyses on ten carcass quality traits; live weight, crude protein,
      crude lipids, crude ash, water holding capacity, drip loss, shear force, CIE L,
      CIE a and CIE b. Phenotypes were regressed on additive and dominance effects for
      each SNP using a simple linear regression model, after adjusting for sex, sire
      and slaughter stage as fixed effects. With the significant SNPs for each trait
      (p<0.001), a stepwise regression procedure was applied to determine the best set
      of SNPs with the additive and/or dominance effects. A total of 106 SNPs, or
      quantitative trait loci (QTL) were detected, and about 32 to 66% of the total
      phenotypic variation was explained by the significant SNPs for each trait. The
      QTL were identified in most porcine chromosomes (SSCs), in which majority of the
      QTL were detected in SSCs 1, 2, 12, 13, 14 and 16. Several QTL clusters were
      identified on SSCs 12, 16 and 17, and a cluster of QTL influencing crude protein,
      crude lipid, drip loss, shear force, CIE a and CIE b were located between 20 and
      29 Mb of SSC12. A pleiotropic QTL for drip loss, CIE L and CIE b was also
      detected on SSC16. These QTL need to be validated in commercial pig populations
      for genetic improvement in meat quality via marker-assisted selection. 

PMID- 25049514
TI  - Protein Profile in Corpus Luteum during Pregnancy in Korean Native Cows.
AB  - Steroidogenesis requires coordination of the anabolic and catabolic pathways of
      lipid metabolism, but the profile of proteins associated with progesterone
      synthesis in cyclic and pregnant corpus luteum (CL) is not well-known in cattle.
      In Experiment 1, plasma progesterone level was monitored in cyclic cows (n = 5)
      and pregnant cows (n = 6; until d-90). A significant decline in the plasma
      progesterone level occurred at d-19 of cyclic cows. Progesterone level in
      abbatoir-derived luteal tissues was also determined at d 1 to 5, 6 to 13 and 14
      to 20 of cyclic cows, and d-60 and -90 of pregnant cows (n = 5 each).
      Progesterone level in d-60 CL was not different from those in d 6 to 13 CL and d
      90 CL, although the difference between d 6 to 13 and d-90 was significant. In
      Experiment 2, protein expression pattern in CL at d-90 (n = 4) was compared with
      that in CL of cyclic cows at d 6 to 13 (n = 5). Significant changes in the level
      of protein expression were detected in 32 protein spots by two-dimensional
      polyacrylamide gel electrophoresis (2-DE), and 23 of them were identified by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). Six proteins were found only in pregnant CL, while the other 17
      proteins were found only in cyclic CL. Among the above 6 proteins, vimentin which
      is involved in the regulation of post-implantation development was included.
      Thus, the protein expression pattern in CL was disorientated from cyclic luteal
      phase to mid pregnancy, and alterations in specific CL protein expression may
      contribute to the maintenance of pregnancy in Korean native cows. 

PMID- 25049516
TI  - Effects of Stocking Density or Group Size on Intake, Growth, and Meat Quality of
      Hanwoo Steers (Bos taurus coreanae).
AB  - This study was conducted to investigate the effects of stocking density or group
      size on feed intake, daily gain, and carcass characteristics of Hanwoo (Korean
      indigenous breed) steers reared from 7 months to 31 months of age. Thirty Hanwoo
      steers were divided into four groups with three replicates each (a total of 12
      pens). In each group, one (G1), two (G2), three (G3), and four steers (G4) per
      pen were allocated as treatments. Pen size was 32.0 m(2), and therefore Hanwoo
      steers in G1, G2, G3, and G4 were reared under different space allowances, i.e.
      32.0, 16.0, 10.6, and 8.0 m(2)/steer, respectively. Steers were reared following
      a conventional beef cattle management method in Korea, and were offered a fixed
      amount of commercial concentrate with ad libitum forages. Results were subjected
      to analysis of variance with stocking density as the main effect, and
      significance was declared at p<0.05. Although total feed intake was not
      significantly altered, it numerically increased in animals of low stocking
      density (G1) compared to those subjected to high stocking density treatment (i.e.
      G4). Feed conversion ratio was higher (p<0.05) in G3 compared to G1 and G2.
      Animals in G1 (low stocking density) grew faster (p<0.05) than those of high
      stocking density (G3 and G4). Back fat thickness, meat yield index, and meat
      yield grade were similar among all levels of stocking density. However,
      longissimus muscle area was larger in G1 and G2 (p<0.01) compared to G3 and G4,
      and animals in G3 produced smaller carcasses (p<0.05). Carcass quality traits,
      including marbling score, meat color, fat color, texture, maturity and meat
      quality grade, as determined by a group of experts, were not significantly
      different among the treatments. In conclusion, lower stocking density resulted in
      increased feed efficiency, daily gain, and carcass weight in Hanwoo steers.
      However it remains unclear whether such differences are the results of stocking
      density or group size, or a combination of both. Nonetheless, these results
      confirm previous studies reporting a negative effect of increased stocking
      density on animal productivity. Further, animal welfare under an intensive
      farming system in relation to economical return is discussed. 

PMID- 25049515
TI  - Effect of alcohol fermented feed on lactating performance, blood metabolites,
      milk Fatty Acid profile and cholesterol content in holstein lactating cows.
AB  - A feeding experiment with 40 lactating Holstein cows and 4 dietary treatments was
      conducted to investigate supplementation with different levels of alcohol
      fermented feed to the TMR on lactating performance, blood metabolites, milk fatty
      acid profile and cholesterol concentration of blood and milk. Forty Holstein
      lactating cows (106+/-24 d post-partum; mean+/-SD) were distributed into four
      groups and randomly assigned to one of four treatments with each containing 10
      cows per treatment. The treatment supplemented with TMR (DM basis) as the control
      (CON), and CON mixed with alcohol-fermented feeds (AFF) at a level of 5%, 10% and
      15% of the TMR as T1, T2 and T3, respectively. Dry matter intake and milk yield
      were not affected by supplementation of AFF. An increased 4% FCM in the milk
      occurred in cows fed T3 diet compared with CON, while T1 and T2 diets decreased
      4% FCM in a dose dependent manner. Supplementation of AFF increased the
      concentration of albumin, total protein (TP), ammonia, and high density
      lipoprotein-cholesterol in serum compared with CON. In contrast, supplementation
      with AFF clearly decreased concentration of blood urea nitrogen (BUN) and total
      cholesterol (TC) compare with CON. AFF supplementation increased the proportion
      of C18:1n9 and C18:2n6 compared to CON. A decrease in the concentration of
      saturated fatty acid (SFA) for T1, T2 and T3 resulted in an increased unsaturated
      fatty acid (USFA) to SFA ratio compared to CON. Concentration of cholesterol in
      milk fat was reduced in proportion to the supplemental level of AFF. Feeding a
      diet supplemented with a moderate level AFF to lactating cows could be a way to
      alter the feed efficiency and fatty acid profile of milk by increasing
      potentially human consumer healthy fatty acid without detrimental effects on feed
      intake and milk production. A substantially decreased cholesterol proportion in
      milk induced by supplementation AFF suggests that alcohol fermented feed may
      improve milk cholesterol levels without any negative effects in lactating cows. 

PMID- 25049517
TI  - Effects of Temperature during Moist Heat Treatment on Ruminal Degradability and
      Intestinal Digestibility of Protein and Amino Acids in Hempseed Cake.
AB  - The objective of this study was to evaluate ruminal degradability and intestinal
      digestibility of crude protein (CP) and amino acids (AA) in hempseed cake (HC)
      that were moist heat treated at different temperatures. Samples of cold-pressed
      HC were autoclaved for 30 min at 110, 120 or 130 degrees C, and a sample of
      untreated HC was used as the control. Ruminal degradability of CP was estimated,
      using the in situ Dacron bag technique; intestinal CP digestibility was estimated
      for the 16 h in situ residue using a three-step in vitro procedure. AA content
      was determined for the HC samples (heat treated and untreated) of the intact
      feed, the 16 h in situ residue and the residue after the three-step procedure.
      There was a linear increase in RUP (p = 0.001) and intestinal digestibility of
      RUP (p = 0.003) with increasing temperature during heat treatment. The 130
      degrees C treatment increased RUP from 259 to 629 g/kg CP, while intestinal
      digestibility increased from 176 to 730 g/kg RUP, compared to the control. Hence,
      the intestinal available dietary CP increased more than eight times. Increasing
      temperatures during heat treatment resulted in linear decreases in ruminal
      degradability of total AA (p = 0.006) and individual AA (p<0.05) and an increase
      in intestinal digestibility that could be explained both by a linear and a
      quadratic model for total AA and most individual AA (p<0.05). The 130 degrees C
      treatment decreased ruminal degradability of total AA from 837 to 471 g/kg, while
      intestinal digestibility increased from 267 to 813 g/kg of rumen undegradable AA,
      compared with the control. There were differences between ruminal AA
      degradability and between intestinal AA digestibility within all individual HC
      treatments (p<0.001). It is concluded that moist heat treatment at 130 degrees C
      did not overprotect the CP of HC and could be used to shift the site of CP and AA
      digestion from the rumen to the small intestine. This may increase the value of
      HC as a protein supplement for ruminants. 

PMID- 25049518
TI  - Effects of synchronization of carbohydrate and protein supply in total mixed
      ration with korean rice wine residue on ruminal fermentation, nitrogen metabolism
      and microbial protein synthesis in holstein steers.
AB  - Three Holstein steers in the growing phase, each with a ruminal cannula, were
      used to test the hypothesis that the synchronization of the hourly rate of
      carbohydrate and nitrogen (N) released in the rumen would increase the amount of
      retained nitrogen for growth and thus improve the efficiency of microbial protein
      synthesis (EMPS). In Experiment 1, in situ degradability coefficients of
      carbohydrate and N in feeds including Korean rice wine residue (RWR) were
      determined. In Experiment 2, three total mixed ration (TMR) diets having
      different rates of carbohydrate and N release in the rumen were formulated using
      the in situ degradability of the feeds. All diets were made to contain similar
      contents of crude protein (CP) and neutral detergent fiber (NDF) but varied in
      their hourly pattern of nutrient release. The synchrony index of the three TMRs
      was 0.51 (LS), 0.77 (MS) and 0.95 (HS), respectively. The diets were fed at a
      restricted level (2% of the animal's body weight) in a 3*3 Latin-square design.
      Synchronizing the hourly supply of energy and N in the rumen did not
      significantly alter the digestibility of dry matter, organic matter, crude
      protein, NDF or acid detergent fiber (ADF) (p>0.05). The ruminal NH3-N content of
      the LS group at three hours after feeding was significantly higher (p<0.05) than
      that of the other groups; however, the mean values of ruminal NH3-N, pH and VFA
      concentration among the three groups were not significantly different (p>0.05).
      In addition, the purine derivative (PD) excretion in urine and microbial-N
      production (MN) among the three groups were not significantly different (p>0.05).
      In conclusion, synchronizing dietary energy and N supply to the rumen did not
      have a major effect on nutrient digestion or microbial protein synthesis (MPS) in
      Holstein steers. 

PMID- 25049519
TI  - Effects of Supplementing Microbially-fermented Spent Mushroom Substrates on
      Growth Performance and Carcass Characteristics of Hanwoo Steers (a Field Study).
AB  - This study evaluated the effect of dietary supplementation of microbially
      fermented spent mushroom substrates (MFSMS) on weight gain, carcass
      characteristics, and economic efficiency of Hanwoo steers. Highly cellulolytic
      bacteria (Enterobacter spp. and Bacillus spp.) isolated from spent mushroom
      substrates (SMS) stacks were inoculated (1% v/v) into the SMS, which was
      anaerobically fermented and fed to the steers for 12.6 months during the growing
      and fattening periods. Growing Hanwoo steers were assigned to the control group
      without supplementation of Microbially-fermented SMS (MFSMS), to a treatment
      group with 50% of MFSMS (1/2 of the ad libitum group), and to a treatment group
      with ad libitum access to SMS (the ad libitum group). All the groups were fed the
      formulated feed and rice straw. The voluntary intake (DM basis) of MFSMS was 1.6
      kg/d during the growing period and 1.4 kg/d during the fattening period. The
      voluntary rice straw intake decreased by 6 to 11%, but the total voluntary DMI
      increased by 7 to 15% with MFSMS fed. The increased DMI with MFSMS
      supplementation resulted in a tendency of increased (p = 0.055) live weight gain
      by 8 to 12% compared with the control group. At slaughtering, the supplementation
      of MFSMS increased (p<0.05) the ribeye area by an average of 10 cm(2). In
      conclusion, feeding MFSMS improved growth performance and carcass traits of
      Hanwoo steers and could successfully replace a part of conventional roughage such
      as rice straw commonly used in Asian countries. 

PMID- 25049520
TI  - Effect of lysine to digestible energy ratio on growth performance and carcass
      characteristics in finishing pigs.
AB  - This experiment was performed to investigate the effects of lysine (Lys) to DE
      ratio on growth performance, and carcass characterics in finishing barrows.
      Ninety six cross-bred finishing barrows ((Landrace*Yorkshire) *Duroc, average BW
      58.25+/-0.48 kg) were assigned as a randomized complete block design by 2 energy
      levels and 4 Lys:DE ratios on the basis of BW to one of 8 treatments with 3
      replications with 4 animals per pen. The levels of DE and Lys:DE ratio for each
      treatment were i) DE 3.35 Mcal/kg, 1.5 g Lys/Mcal DE, ii) DE 3.35 Mcal/kg, 1.8 g
      Lys/Mcal DE, iii) DE 3.35 Mcal/kg, 2.1 g Lys/Mcal DE, iv) DE 3.35 Mcal/kg, 2.4 g
      Lys/Mcal DE, v) DE 3.60 Mcal/kg, 1.5 g Lys/Mcal DE, vi) DE 3.60 Mcal/kg, 1.8 g
      Lys/Mcal DE, vii) DE 3.60 Mcal/kg, 2.1 g Lys/Mcal DE, viii) DE 3.60 Mcal/kg, 2.4
      g Lys/Mcal DE. During finishing period from 58 kg to 103 kg of BW, increased
      energy density in the diet increased (p<0.05) ADG and gain:feed ratio, but did
      not influence ADFI. As Lys:DE ratio was increased, ADG, ADFI and gain:feed ratio
      were improved in finishing barrows (p<0.05). There were positive interactions
      (p<0.05) between carcass weight, grade, and backfat thickness and energy density
      and Lys level (p<0.05). In conclusion, data from our current study suggest that
      maximum yields including ADG, gain:feed ratio, carcass weight and grade can be
      achieved by administrating finishing pigs with an ideal Lys:DE ratio, Lys 2.1
      g/DE Mcal. 

PMID- 25049521
TI  - Effects of Replacement of Fish Meal by Soy Protein Isolate on the Growth,
      Digestive Enzyme Activity and Serum Biochemical Parameters for Juvenile Amur
      Sturgeon (Acipenser schrenckii).
AB  - An 8-wk experiment was conducted to evaluate the effect of replacing fish meal
      (FM) with soy protein isolate (SPI) on the growth, digestive enzyme activity and
      serum biochemical parameters of juvenile Amur sturgeon (Acipenser schrenckii).
      SPI was used to replace 0, 25, 50, 62.5, 75, 87.5, 100% of dietary FM and 100%
      replacement supplemented crystalline amino acid. Healthy sturgeon with an average
      initial weight of 26.38+/-0.24 g were randomly assigned to 24 aquaria (8
      treatments with triplicates each) at an initial stocking density of 11 fish per
      aquarium and cultured for 8 wks. The results showed that 75.00% or more
      substitution resulted in a poor weight gain rate, feed conversion ratio and
      survival rate compared to that of fish fed the control diet (p<0.05), whereas no
      significant differences were observed between diets of 25.00% to 62.50%
      substitution. Protease, lipase and amylase activity in foregut, mid-gut and
      hindgut were significantly (p<0.05) decreased by diets where SPI replacement
      levels were 62.50% or more. Levels of serum total protein (TP) and globulin
      decreased significantly from 21.03, 10.34 to 14.05, 5.63 g/L with the increasing
      dietary SPI (p<0.05), but alkaline phosphatase activity significantly increased
      (p<0.05). In addition, supplemental crystalline amino acid in the FM absence diet
      did not improve growth performance, intestine digestive enzyme activities and
      serum biochemical parameters. In conclusion, the results from this study showed
      adverse effects of inclusion of SPI in diets on growth performance, feed
      utilization and serum biochemical parameters in juvenile Amur sturgeon. Based on
      WGR and replacement ratio presented in this report, a 57.64% replacement level
      was recommended. 

PMID- 25049522
TI  - Effects of Anti-diarrhoeal Herbs on Growth Performance, Nutrient Digestibility,
      and Meat Quality in Pigs.
AB  - Two studies were conducted to investigate the effects of anti-diarrhoeal herbs on
      growth performance, nutrient digestibility, and meat quality in pigs. In Exp 1,
      150 weanling-growing piglets (average BW = 7.5+/-0.24 kg, average age = 27+/-1 d)
      were allotted into one of the five dietary treatments, including: i) CON, basal
      diet, ii) DP, basal diet+1 g/kg date pits, iii) JH, basal diet+0.5 g/kg Japanese
      honeysuckle, iv) HCT, basal diet+1 g/kg houttuynia cordata thunb, and v) LE,
      basal diet+1 g/kg laquer tree extract. From wk 0 to 5, the JH, HCT and LE groups
      presented higher (p<0.05) ADFI, ADG and gain/feed ratio (G/F) than CON and DP
      groups. During wk 5 to 10, Pigs fed JH, HCT and LE diets indicated higher
      (p<0.05) ADG and ADFI than the pigs fed CON and DP diets. During the entire
      experimental period, a significant increase of ADG appeared in JH, HCT and LE
      (p<0.05). Pigs fed JH, HCT and LE diets got a higher (p<0.05) ADFI than the pigs
      fed CON and DP diets. Pigs fed diets with supplementations of herb additives
      revealled lower (p<0.05) score of diarrhea pigs during d 2 to d 6 compared with
      pigs fed CON diet. In Exp 2, 60 growing-finishing barrows and gilts (average BW =
      54.10+/-1.20 kg, average age = 54+/-3 d) were allotted to three treatments: i)
      CON, basal diet; ii) YG, basal diet+1 g/kg yellow ginger and iii) HR, basal
      dietary+1 g/kg hoantchy root, respectively. From wk 0 to 5, Dietary
      supplementation of YG and HR enhanced (p<0.05) ADG. No difference was found
      between YG and HR treatments. During, wk 5 to 10, ADG also was observed higher in
      YG and HR treatments than CON group (p<0.05). Additional, YG had the highest ADG
      (p<0.05) among treatments. There was always an increase of ADG in YG and HR
      (p<0.05) through all periods. HR treatment showed a lower (p<0.05) score of
      diarrhoeal pigs on d 1and d 2 compared with CON treatment. Pigs fed YG and HR
      diets had a higher (p<0.05) longissimus muscle area (LMA) than pigs fed CON diet.
      In conclusion, anti-diarrhoeal herbs can improve growth performance, and prevent
      diarrhea incidence in pigs, it can also increase LMA in finishing pigs. 

PMID- 25049523
TI  - Effect of Red Pepper (Capsicum frutescens) Powder or Red Pepper Pigment on the
      Performance and Egg Yolk Color of Laying Hens.
AB  - Two experiments were conducted to study the effects of red pepper (Capsicum
      frutescens) powder or red pepper pigment on the performance and egg yolk color of
      laying hens. In Exp. 1, 210, thirty-wk old, Hy-line Brown laying hens were fed
      one of seven diets containing 0.3, 0.6, 1.2, 2.0, 4.8 or 9.6 ppm red pepper
      pigment or 0.3 ppm carophyll red. Each diet was fed to three replicate batteries
      of hens with each battery consisting of a row of five cages of hens with two hens
      per cage (n = 3). In Exp. 2, 180, thirty-wk old, Hyline Brown laying hens, housed
      similarly to those in Exp. 1, were fed an unsupplemented basal diet as well as
      treatments in which the basal diet was supplemented with 0.8% red pepper powder
      processed in a laboratory blender to an average particle size of 300 MUm, 0.8%
      red pepper powder processed as a super fine powder with a vibrational mill (44
      MUm) and finally 0.8% red pepper powder processed as a super fine powder with a
      vibrational mill but mixed with 5% Na2CO3 either before or after grinding. A diet
      supplemented with 0.3 ppm carophyll red pigment was also included (n = 3). In
      both experiments, hens were fed the red pepper powder or pigment for 14 days.
      After feeding of the powder or pigment was terminated, all hens were fed the
      basal diet for eight more days to determine if the dietary treatments had any
      residual effects. In Exp. 1, there were no differences in egg-laying performance,
      feed consumption or feed conversion ratio due to inclusion of red pepper pigment
      in the diet. Average egg weight was higher (p<0.05) for birds fed 1.2, 2.4 or 9.6
      ppm red pepper pigment than for birds fed the diet containing 0.3 ppm red pepper
      pigment. On d 14, egg color scores increased linearly as the level of red pepper
      pigment in the diet increased. In Exp. 2, feeding red pepper powder did not
      affect egg-laying performance, feed consumption or feed conversion ratio
      (p>0.05). However, compared with the control group, supplementation with all of
      the red pepper powder treatments increased egg weight (p<0.05). All the red
      pepper powder treatments also increased (p<0.05) the yolk color score compared
      with the control. The results of the present study suggest that both red pepper
      powder and pigment are effective feed additives for improving egg yolk color for
      laying hens. 

PMID- 25049524
TI  - Effect of dietary sodium nitrate consumption on egg production, egg quality
      characteristics and some blood indices in native hens of west azarbaijan
      province.
AB  - The aim of the study was to evaluate the effect of sodium nitrate consumption on
      egg quality and quantity, and some blood parameters of native breeder hens of
      West Azerbaijan province. One hundred native hens were used from wk 25 to 32 of
      age. These birds were divided into two groups. One group was fed the control diet
      (CD) but the other fed the same diet supplemented with 4.2 g/kg sodium nitrate
      (ND). After 2 wks of adaptation, eggs were collected daily and egg mass and egg
      production were measured weekly for five weeks. To assess the egg quality
      parameters, two eggs from each replicate pen were collected for three consecutive
      days each week. At the end of experimental period (wk 32 of age), blood samples
      of 5 birds per replicate were collected from the wing vein into anticoagulant
      tubes. Dietary sodium nitrate didn't affect the egg production, shell stiffness,
      shell thickness and Haugh unit (p>0.05) but it decreased the both egg production
      and egg mass during the last three weeks (wks 30, 31 and 32) (p<0.05).
      Furthermore, a treatment effect was observed for yolk colour (p<0.05). Both the
      egg production and egg mass were increased over time (p<0.05). No significant
      treatment*time interaction was observed for egg weight, egg production and egg
      mass (p>0.05). No effect of time or treatment*time were observed for shell
      stiffness (p>0.05). Over time, shell thickness was decreased while Haugh unit
      increased (p<0.05). None of the blood TP and TG or the activity of ALT, AST and
      LDH enzymes were affected by dietary consumption of sodium nitrate at wk 32 of
      age (p>0.05). Sodium nitrite decreased both the TAC and TC at wk 32 of age
      (p<0.001). It was concluded that the lower body antioxidant capacity of nitrate
      fed birds resulted in the lower performance (egg weight, egg production and egg
      mass). 

PMID- 25049525
TI  - Effects of adding essential oil to the diet of weaned pigs on performance,
      nutrient utilization, immune response and intestinal health.
AB  - The objective of this study was to evaluate the effects of adding essential oils
      to the diet of weaned pigs on performance, nutrient utilization, immune response
      and intestinal health. A total of 96 weaning pigs (8.37+/-1.58 kg) were allotted
      to one of three dietary treatments. The treatments consisted of an unsupplemented
      basal diet (negative control, NC) or similar diets supplemented with 0.01% of an
      essential oil product which contained 18% thymol and cinnamaldehyde (EOD) as well
      as a diet supplemented with 0.19% of an antibiotic mixture which provided 150 ppm
      chlortetracycline, 80 ppm colistin sulfate and 50 ppm kitasamycin (positive
      control, PC). Each treatment was provided to eight pens of pigs with four pigs
      per pen. Over the entire 35 d experiment, ADG and fecal score were improved
      (p<0.05) for pigs fed the PC and EOD compared with the NC. Dry matter and crude
      protein digestibility as well as lymphocyte proliferation for pigs fed the PC and
      EOD diets were increased significantly compared with NC (p<0.05). IGF-I levels in
      plasma were significantly increased (p<0.05) in pigs fed the PC diet compared
      with pigs fed the NC diet. Interleukin-6 concentration was lower (p<0.05) and the
      tumor necrosis factor-alpha level was higher (p<0.05) in the plasma of pigs fed
      the EOD diet than the NC diet. Plasma total antioxidant capacity level increased
      (p<0.05) in pigs fed the EOD diet compared with pigs fed the NC. Villus height to
      crypt depth ratio in the jejunum was greater (p<0.05) in pigs fed the PC and EOD
      diets than the NC. The numbers of E. coli in the cecum, colon and rectum were
      reduced (p<0.05) in pigs fed the PC and EOD diets compared with the control. In
      the colon, the ratio of Lactobacilli to E. coli was increased (p<0.05) in pigs
      fed the EOD diet compared with NC diet. Total aerobe numbers in the rectum were
      decreased (p<0.05) in pigs fed the PC and EOD diets compared with the control.
      Collectively, these results indicate that blends of essential oils could be a
      candidate for use as an alternative to traditional antibiotics in weaning pig
      diets. 

PMID- 25049526
TI  - Solid waste from Swine wastewater as a fuel source for heat production.
AB  - This study was to evaluate the feasibility of recycling the solids separated from
      swine wastewater treatment process as a fuel source for heat production and to
      provide a data set on the gas emissions and combustion properties. Also, in this
      study, the heavy metals in ash content were analyzed for its possible use as a
      fertilizer. Proximate analysis of the solid recovered from the swine wastewater
      after flocculation with organic polymer showed high calorific (5,330.50 kcal/kg)
      and low moisture (15.38%) content, indicating that the solid separated from swine
      wastewater can be used as an alternative fuel source. CO and NOx emissions were
      found to increase with increasing temperature. Combustion efficiency of the
      solids was found to be stable (95 to 98%) with varied temperatures.
      Thermogravimetry (TG) and differential thermal analysis (DTA) showed five thermal
      effects (four exothermic and one endothermic), and these effects were
      distinguished in three stages, water evaporation, heterogeneous combustion of
      hydrocarbons and decomposition reaction. Based on the calorific value and
      combustion stability results, solid separated from swine manure can be used as an
      alternative source of fuel, however further research is still warranted regarding
      regulation of CO and NOx emissions. Furthermore, the heavy metal content in ash
      was below the legal limits required for its usage as fertilizer. 

PMID- 25049527
TI  - Comparison of pork quality and sensory characteristics for antibiotic free
      yorkshire crossbreds raised in hoop houses.
AB  - The objective of this study was to compare pork characteristics and to determine
      consumer acceptability of pork chops from antibiotic free Yorkshire crossbreds
      sired by Berkshire (BY), Large Black (LBY), Tamworth (TY) or Yorkshire (YY) boars
      and reared in hoop houses. The experiments were conducted at the North Carolina
      Agricultural and Technical State University (NCA&TSU) Farm in Greensboro, NC and
      the Cherry Research Station Center for Environmental Farming Systems (CEFS)
      Alternative Swine Unit in Goldsboro, NC (source of antibiotic free Yorkshire sows
      used at both places). Twenty-four sows were artificially inseminated at each
      location in each of three trials. Litters were weaned at 4 wks old, and reared
      within deep-bedded outdoor hoop houses. To compare pork characteristics, 104
      randomly selected animals were harvested at a USDA-inspected abattoir at
      approximately 200 d of age. Variables measured included pH, color score, L*, a*,
      b*, marbling score, drip loss, hot carcass weight, backfat thickness (BF), loin
      muscle area (LMA), and slice shear force. Sensory panel tests were also conducted
      at two time periods. The data was analyzed with GLM in SAS 9.01 including
      location, trial, and sire breed as fixed effects. Backfat thickness, LMA, color
      score and a* were different among breeding groups (p<0.05). The LBY pigs had
      thicker backfat and smaller LMA than the other breed types. The TY and YY had
      less backfat than all other breed groups. Color score was lower for YY than BY
      and LBY but intermediate for TY. The a* was lower for TY than other breeds except
      LBY which was intermediate. For one sensory panel test, YY pork was more
      preferred overall as well as for juiciness and texture compared to BY and LBY
      (p<0.05), but no impact of breed type was noted for the other test, with values
      similar for BY, LBY, TY and YY pork. This information may help small farmers make
      decisions about breed types to use for outdoor production. 

PMID- 25049528
TI  - Effect of dietary supplementation of the combination of gallic and linoleic Acid
      in thigh meat of broilers.
AB  - This study was performed to investigate the combined effect of dietary
      supplementation of gallic and linoleic acid (GL) on the antioxidative effect and
      quality of thigh meat from broilers. Broilers received 3 dietary treatments: i)
      commercial finisher diet (control), ii) 0.5% GL (gallic:linoleic acid = 1 M:1 M),
      and iii) 1.0% GL during the 22 to 36 d. The pH value of broiler thigh meat was
      increased by GL supplementation. Water holding capacity of the thigh meat was
      enhanced by the 1.0% dietary GL supplementation. Antioxidative effect (total
      phenolic content, DPPH radical scavenging activity, ABTS(+) reducing activity,
      reducing power, and TBARS value) in the thigh from the broilers improved
      significantly with 1.0% GL. Linoleic acid and docosahexaenoic acids were higher
      in the broilers fed both levels of dietary GL. However, volatile basic nitrogen
      content and microbiological quality was not shown to be different between control
      and treated group. Results indicate that 1.0% dietary supplementation of GL can
      improve the antioxidant activity of broiler thigh meat and may enhance the meat
      quality. 

PMID- 25049530
TI  - MHC-DQB1 Variation and Its Association with Resistance or Susceptibility to
      Cystic Echinococcosis in Chinese Merino Sheep.
AB  - Cystic echinococcosis (CE), one of the world's most geographically widespread
      diseases, still represents a considerable economic and public health
      significance, although a variety of methods has been used to control the disease.
      It has been demonstrated that genetic factors, especially variations in MHC loci,
      can influence the outcome of CE infection in the human population. The study
      described here was designed to determine whether variation in MHC-DQB1 was
      associated with susceptibility or resistance to CE in sheep. If so, it would lay
      a theoretical foundation for breeding disease resistance sheep in future. This
      study was carried out on 204 Chinese Merino sheep, including 101 CE sheep and 103
      healthy controls. The polymorphism of MHC-DQB1 exon 2 was detected by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and x
      (2) test was used to compare genotype frequencies between CE sheep and healthy
      controls. A total of 22 alleles and 42 genotypes were identified in DQB1 exon 2
      in Chinese Merino sheep. In addition, x (2) test showed that frequencies of DQB1
      TaqIaa and DQB1-HaeIIInn genotypes were significantly higher in the healthy group
      (82.5% and 57.3%, respectively) than that in the CE group (57.4% and 28.9%,
      respectively) (both p values = 0, OR = 0.286, 0.303, respectively), suggesting
      that these genotypes appeared to be associated with resistance to CE. Whereas,
      frequencies of DQB1-TaqIab and DQB1-HaeIIImn genotypes were significantly higher
      in the CE group (36.9% and 32.0%, respectively), as compared with the healthy
      group (16.5% and 11.15%, respectively) (p = 0.001, 0.001 and OR = 2.963, 3.629,
      respectively), indicating that these genotypes might be associated with
      susceptibility to CE. It is concluded that the genetic polymorphism within MHC
      DQB1 might influence immune responses to pathogens, thus leading to the
      development of CE or protection against CE in Chinese Merino sheep, which would
      pave the way for breeding disease resistance sheep in future. 

PMID- 25049529
TI  - Porcine LMNA Is a Positional Candidate Gene Associated with Growth and Fat
      Deposition.
AB  - Crosses between Korean and Landrace pigs have revealed a large quantitative trait
      loci (QTL) region for fat deposition in a region (89 cM) of porcine chromosome 4
      (SSC4). To more finely map this QTL region and identify candidate genes for this
      trait, comparative mapping of pig and human chromosomes was performed in the
      present study. A region in the human genome that corresponds to the porcine QTL
      region was identified in HSA1q21. Furthermore, the LMNA gene, which is tightly
      associated with fat augmentation in humans, was localized to this region.
      Radiation hybrid (RH) mapping using a Sus scrofa RH panel localized LMNA to a
      region of 90.3 cM in the porcine genome, distinct from microsatellite marker
      S0214 (87.3 cM). Two-point analysis showed that LMNA was linked to S0214, SW1996,
      and S0073 on SSC4 with logarithm (base 10) of odds scores of 20.98, 17.78, and
      16.73, respectively. To clone the porcine LMNA gene and to delineate the genomic
      structure and sequences, including the 3'untranslated region (UTR), rapid
      amplification of cDNA ends was performed. The coding sequence of porcine LMNA
      consisted of 1,719 bp, flanked by a 5'UTR and a 3'UTR. Two synonymous single
      nucleotide polymorphisms (SNPs) were identified in exons 3 and 7. Association
      tests showed that the SNP located in exon 3 (A193A) was significantly associated
      with weight at 30 wks (p<0.01) and crude fat content (p<0.05). This association
      suggests that SNPs located in LMNA could be used for marker-assisted selection in
      pigs. 

PMID- 25049531
TI  - Estimation of relative economic weights of hanwoo carcass traits based on carcass
      market price.
AB  - The objective of this study was to estimate economic weights of Hanwoo carcass
      traits that can be used to build economic selection indexes for selection of
      seedstocks. Data from carcass measures for determining beef yield and quality
      grades were collected and provided by the Korean Institute for Animal Products
      Quality Evaluation (KAPE). Out of 1,556,971 records, 476,430 records collected
      from 13 abattoirs from 2008 to 2010 after deletion of outlying observations were
      used to estimate relative economic weights of bid price per kg carcass weight on
      cold carcass weight (CW), eye muscle area (EMA), backfat thickness (BF) and
      marbling score (MS) and the phenotypic relationships among component traits.
      Price of carcass tended to increase linearly as yield grades or quality grades,
      in marginal or in combination, increased. Partial regression coefficients for MS,
      EMA, BF, and for CW in original scales were +948.5 won/score, +27.3 won/cm(2), 
      95.2 won/mm and +7.3 won/kg when all three sex categories were taken into
      account. Among four grade determining traits, relative economic weight of MS was
      the greatest. Variations in partial regression coefficients by sex categories
      were great but the trends in relative weights for each carcass measures were
      similar. Relative economic weights of four traits in integer values when
      standardized measures were fit into covariance model were +4:+1:-1:+1 for
      MS:EMA:BF:CW. Further research is required to account for the cost of production
      per unit carcass weight or per unit production under different economic
      situations. 

PMID- 25049532
TI  - A Whole Genome Association Study to Detect Single Nucleotide Polymorphisms for
      Blood Components (Immunity) in a Cross between Korean Native Pig and Yorkshire.
AB  - The purpose of this study was to detect significant SNPs for blood components
      that were related to immunity using high single nucleotide polymorphism (SNP)
      density panels in a Korean native pig (KNP)*Yorkshire (YK) cross population. A
      reciprocal design of KNP*YK produced 249 F2 individuals that were genotyped for a
      total of 46,865 available SNPs in the Illumina porcine 60K beadchip. To perform
      whole genome association analysis (WGA), phenotypes were regressed on each SNP
      under a simple linear regression model after adjustment for sex and slaughter
      age. To set up a significance threshold, 0.1% point-wise p value from F
      distribution was used for each SNP test. Among the significant SNPs for a trait,
      the best set of SNP markers were determined using a stepwise regression procedure
      with the rates of inclusion and exclusion of each SNP out of the model at 0.001
      level. A total of 54 SNPs were detected; 10, 6, 4, 4, 5, 4, 5, 10, and 6 SNPs for
      neutrophil, lymphocyte, monocyte, eosinophil, basophil, atypical lymph,
      immunoglobulin, insulin, and insulin-like growth factor-I, respectively. Each set
      of significant SNPs per trait explained 24 to 42% of phenotypic variance. Several
      pleiotropic SNPs were detected on SSCs 4, 13, 14 and 15. 

PMID- 25049533
TI  - Pro-apoptotic Effect of Pifithrin-alpha on Preimplantation Porcine In vitro
      Fertilized Embryo Development.
AB  - The aim of this study was to investigate the impact of a reported p53 inhibitor,
      pifithrin-alpha (PFT-alpha), on preimplantation porcine in vitro fertilized (IVF)
      embryo development in culture. Treatment of PFT-alpha was administered at both
      early (0 to 48 hpi), and later stages (48 to 168 hpi) of preimplantation
      development, and its impact upon the expression of five genes related to
      apoptosis (p53, bak, bcl-xL, p66Shc and caspase3), was assessed in resulting d 7
      blastocysts, using real-time quantitative PCR. Total cell numbers, along with the
      number of apoptotic nuclei, as detected by the in situ cell death detection
      assay, were also calculated on d 7 in treated and non-treated control embryos.
      The results indicate that PFT-alpha, when administered at both early and later
      stages of porcine IVF embryo development, increases the incidence of apoptosis in
      resulting blastocysts. When administered at early cleavage stages, PFT-alpha
      treatment was shown to reduce the developmental competence of porcine IVF
      embryos, as well as reducing the quality of resulting blastocysts in terms of
      overall cell numbers. In contrast, at later stages, PFT-alpha administration
      resulted in marginally increased blastocyst development rates amongst treated
      embryos, but did not affect cell numbers. However, PFT-alpha treatment induced
      apoptosis and apoptotic related gene expression, in all treated embryos,
      irrespective of the timing of treatment. Our results indicate that PFT-alpha may
      severely compromise the developmental potential of porcine IVF embryos, and is a
      potent apoptotic agent when placed into porcine embryo culture media. Thus,
      caution should be exercised when using PFT-alpha as a specific inhibitor of p53
      mediated apoptosis, in the context of porcine IVF embryo culture systems. 

PMID- 25049535
TI  - Use of Awamori-pressed Lees and Tofu Lees as Feed Ingredients for Growing Female
      Goats.
AB  - Okinawan Awamori is produced by fermenting steamed indica rice with black mold,
      yeast, and water. Awamori-pressed lees is a by-product of the Awamori production
      process. Tofu lees is a by-product of the Tofu production process. This research
      consisted of two experiments conducted to elucidate whether or not dried Awamori
      pressed lees and Tofu lees can be used as a mixed feed ingredient for raising
      female goats. In experiment 1, digestion trials were conducted to ascertain the
      nutritive values of dried Awamori-pressed lees and dried Tofu lees for goats. The
      digestible crude protein (DCP) and total digestible nutrients (TDN) contents of
      dried Awamori-pressed lees and Tofu lees were 22.5%, 22.5% (DCP), and 87.2%,
      94.4% (TDN) respectively. In experiment 2, 18 female goats (Japanese
      Saanen*Nubian, three months old, body weight 15.4+/-0.53 kg) were divided into
      three groups of six animals (control feed group (CFG), Awamori-pressed lees mixed
      feed group (AMFG), Tofu lees mixed feed group (TMFG)). The CFG control used feed
      containing 20% soybean meal as the main protein source, while the AMFG and TMFG
      treatments used feed mixed with 20% dried Awamori-pressed lees or dried Tofu
      lees. The groups were fed mixed feed (volume to provide 100 g/d increase in body
      weight) twice a day (10:00, 16:00). The klein grass hay and water was given ad
      libitum. The hay intake was measured at 08:00 and 16:00. Body weight and size
      measurements were taken once a month. At the end of the experiment, a blood
      sample was drawn from the jugular vein of each animal. The DCP and TDN intakes in
      AMFG and TMFG showed no significant difference to the CFG. Cumulative
      measurements of growth in body weight, withers height, chest depth, chest girth,
      and hip width over the 10 mo period in the AMFG and TMFG were similar to the CFG.
      By contrast, cumulative growth in body length and hip height in the AMFG and TMFG
      tended to be larger than the CFG. Cumulative growth in chest width in the AMFG
      was significantly larger (p<0.05) than the CFG. Blood parameter values were
      similar to those in normal goats reported by other scientists. The coats of the
      AMFG and TMFG animals looked shinier than the animals in the CFG. The results
      demonstrate that dried Awamori-pressed lees and Tofu lees can be used as a feed
      ingredient for the raising female goats. 

PMID- 25049534
TI  - Effect of harvesting frequency, variety and leaf maturity on nutrient
      composition, hydrogen cyanide content and cassava foliage yield.
AB  - The experiment studied the effect of harvesting frequencies and varieties on
      yield, chemical composition and hydrogen cyanide content in cassava foliage.
      Foliage from three cassava varieties, K94 (very bitter), K98-7 (medium bitter)
      and a local (sweet), were harvested in three different cutting cycles, at 3, 6
      and 9 months; 6 and 9 months and 9 months after planting, in a 2-yr experiment
      carried out in Hanoi, Vietnam. Increasing the harvesting frequency increased dry
      matter (DM) and crude protein (CP) production in cassava foliage. The K94 variety
      produced higher foliage yields than the other two varieties. Dry matter, neutral
      detergent fibre (NDF), acid detergent fibre (ADF) and total tannin content
      increased with months to the first harvest, whereas CP content decreased.
      Hydrogen cyanide (HCN) content was lower at the first harvest than at later
      harvests for all cutting cycles. At subsequent harvests the content of total
      tannins tended to decline, while HCN content increased (p<0.05). Chemical
      composition differed somewhat across varieties except for total tannins and ash.
      Dry matter, NDF, ADF and total tannins were higher in fully matured leaves, while
      CP and HCN were lower in developing leaves. 

PMID- 25049537
TI  - Growth and Nutrient Utilization in Kids Fed Expander-extruded Complete Feed
      Pellets Containing Red Gram (Cajanus cajan) Straw.
AB  - A growth and digestibility study was conducted using Osmanabadi goat male kids by
      feeding complete diets in the form of mash or expander extruded pellets
      containing different levels of red gram (Cajanus cajan) straw (RGS). Two iso
      nitrogenous complete diets were prepared by incorporating RGS at 35% and 50%
      levels. Half the quantity of each complete mash feed was then converted into
      pellets through expander extruder processing. Thirty two kids of 4 to 5 months
      age were divided into four groups of eight each and were fed for 150 d with four
      experimental diets (T1: mash with 35% RGS, T2: mash with 50% RGS, T3: pellets
      with 35% RGS and T4: pellets with 50% RGS). Pelleting of complete diets
      significantly (p<0.001) increased the voluntary feed intake (671.45 vs 426.28
      g/d) at both levels of RGS in the feeds. Average daily gain (ADG, g/d) also
      increased significantly (p<0.001) from 48.79 in kids fed mash diet to 71.29 in
      those fed with pelleted diets. Feed conversion efficiency (dry matter (DM)
      intake: weight gain) was comparable among all the treatment groups. Digestibility
      of nutrients was not affected by pelleting of the feeds whereas, increasing the
      level of inclusion of RGS in feeds from 35% to 50% decreased (p<0.05) the
      digestibility of DM and crude protein (CP) resulting in lower (p<0.001)
      metabolizable energy (ME) content (MJ/kg DM) in feeds with 50% RGS (7.93 vs
      8.75). Daily intake (MJ/kg BW(-0.75)) of ME decreased (p<0.05) in feeds
      containing 50% RGS while pelleting of feeds increased (p<0.05) the intake of DM,
      CP, digestible crude protein (DCP) and ME. It is inferred that expander extruder
      pelleting can efficiently utilize RGS up to 50% level in complete diets for
      growing goat kids. 

PMID- 25049536
TI  - The Effect of Body Energy Reserve Mobilization on the Fatty Acid Profile of Milk
      in High-yielding Cows.
AB  - We investigated the effect of the amount of body condition loss in the dry period
      and early lactation in 42 high-yielding Holstein-Friesian cows on milk yield and
      the share of fatty acids in milk fat. Energy reserves were estimated based on the
      body condition scoring (BCS) and backfat thickness (BFT). Milk yield and milk
      composition were determined over 305-d lactation. From d 6 to 60 of lactation,
      the concentrations of 43 fatty acids in milk fat were determined by gas
      chromatography. Cows were categorized based on body condition loss from the
      beginning of the dry period to the lowest point of the BCS curve in early
      lactation into three groups: low condition loss group (L) <=0.5 points (n = 14);
      moderate condition loss group (M) 0.75 to 1.0 points (n = 16) and high condition
      loss group (H) >1.0 points (n = 12). Cows whose body energy reserves were
      mobilized at 0.8 BCS and 11 mm BFT, produced 12,987 kg ECM over 305-d lactation,
      i.e. 1,429 kg ECM more than cows whose BCS and BFT decreased by 0.3 and 5 mm,
      respectively. In group H, milk yield reached 12,818 kg ECM at body fat reserve
      mobilization of 1.3 BCS and 17 mm BFT. High mobilization of body fat reserves led
      to a significant (approx. 5%) increase in the concentrations of monounsaturated
      fatty acids-MUFA (mostly C18:1 cis-9, followed by C18:1 trans-11), a significant
      decrease in the levels of fatty acids adversely affecting human health, and a
      drop in the content of linoleic acid, arachidonic acid and docosahexaenoic acid
      in milk fat. In successive weeks of lactation, an improved energy balance
      contributed to a decrease in the concentrations of unsaturated fatty acids (UFA)
      and an increase in the conjugated linoleic acid (CLA) content of milk fat. 

PMID- 25049538
TI  - Effect of Fibre Level and Fibre Source on Gut Morphology and Micro-environment in
      Local (Mong Cai) and Exotic (Landrace*Yorkshire) Pigs.
AB  - The effect of genotype, fibre level and fibre source on gut morphology,
      environment and microflora was studied using 18 Mong Cai (MC) and 18
      Landrace*Yorkshire (LY) pigs, aged around 60 d. The diets were based on maize,
      rice bran, soybean meal, fish meal and soybean oil, and cassava residue (CR) or
      brewer's grain (BG) as fibrous ingredient sources in the high-fibre diets (HF). A
      low-fibre diet (LF), containing around 200 g NDF/kg dry matter (DM), was
      formulated without CR and BG as feed ingredients. The HF diets (HF-CR and HF-BG)
      were formulated to contain around 270 g NDF/kg DM. The experiment was arranged
      according to a 2*3 factorial completely randomized design with six replications,
      and lasted 30 d. Crypt density in ileum was lowest (p<0.05) and villus height in
      jejunum and ileum were the greatest (p<0.05) in pigs fed diet HF-BG. Villus width
      in ileum was greatest in pigs fed diets HF-CR and HF-BG (p<0.05). Lactic acid
      bacteria (LAB) counts in stomach were greatest (p<0.05) and E. coli counts in
      ileum and colon were lowest (p<0.05) in pigs fed diet HF-CR. The concentration of
      total organic acids in ileum, caecum and colon were greatest (p<0.05), and pH in
      ileum and colon were lowest (p<0.05) in pigs fed diet HF-CR. Crypt density in
      ileum was lowest, and villus height in ileum and villus width in jejunum and
      ileum was greatest in LY pigs (p<0.05). LAB counts in stomach and ileum were
      greatest, and E. coli counts in ileum were lowest in MC pigs (p<0.05). The
      concentration of total organic acids in ileum, caecum and colon were greatest
      (p<0.05) and pH lowest (p<0.05) in MC pigs. 

PMID- 25049539
TI  - Effects of replacing soybean meal with fermented rapeseed meal on performance,
      serum biochemical variables and intestinal morphology of broilers.
AB  - This trial was performed to study the effects of replacing soybean meal (SBM)
      with fermented rapeseed meal (RSM) on growth performance, serum biochemistry
      variable and intestinal morphology of broilers. A total of 640 d-old Arbor Acres
      broiler chicks were randomly allocated to 4 dietary treatments, 4 pens per
      treatment and 40 birds per pen for a 6-wk feeding trial. In the four treatment
      groups, fermented RSM replaced soybean meal at 0, 5, 10, and 15%, respectively.
      On 21 d and 42 d, two birds from each pen were randomly selected and slaughtered.
      Blood samples and sections of duodenum, jejunum, and ileum were collected for
      measurement of serum biochemical variables and intestinal morphology,
      respectively. Results showed that body weight gain (BWG) and feed conversion (FC)
      were significantly (p<0.01) poorer for birds fed the 15% fermented RSM diet than
      those fed with 0, 5 and 10% fermented RSM diets during all periods. Compared with
      0 and 5% fermented RSM groups, IgG content in the serum of birds in 10 and 15%
      fermented RSM groups was improved (p<0.01) urea nitrogen content of serum was
      reduced (p<0.01) during both growing and finishing periods. However, IgM,
      phosphorus and calcium levels increased (p<0.05) only during the growing period.
      Increased (p<0.05) villus height was observed in the duodenum and jejunum of
      broilers fed the diet with 10% fermented RSM. In addition, villus height to crypt
      depth ratio in the jejunum was significantly higher (p<0.01) for birds fed the
      diet with 10% fermented RSM than for those fed diets with 0, 5 and 15% fermented
      RSM. The present results suggest that RSM fermented with Lactobacillus fermentum
      and Bacillus subtilis is a promising alternative protein source and that it could
      be safely used replace up to 10% SBM in broiler diets. 

PMID- 25049540
TI  - Effect of fermented chlorella supplementation on growth performance, nutrient
      digestibility, blood characteristics, fecal microbial and fecal noxious gas
      content in growing pigs.
AB  - A total of 96 growing pigs ((Landrace*Yorkshire)*Duroc; BW = 26.58+/-1.41 kg)
      were used in a 6-wk feeding trail to evaluate the effects of fermented chlorella
      (FC) supplementation on growth performance, nutrient digestibility, blood
      characteristics, fecal microbial and fecal noxious gas content in growing pigs.
      Pigs were randomly allotted into 1 of 4 dietary treatments with 6 replicate pens
      (2 barrows and 2 gilts) per treatment. Dietary treatments were: i) negative
      control (NC), basal diet (without antibiotics); ii) positive control (PC),
      NC+0.05% tylosin; iii) (fermented chlorella 01) FC01, NC+0.1% FC, and iv)
      fermented chlorella 02 (FC02), NC+0.2% FC. In this study, feeding pigs PC or FC01
      diets led to a higher average daily gain (ADG) and dry matter (DM) digestibility
      than those fed NC diet (p<0.05), whereas the inclusion of FC02 diet did not
      affect the ADG and DM compared with the NC group. No difference (p>0.05) was
      observed on the body weight, average daily feed intake (ADFI), gain:feed (G:F)
      ratio, the apparent total tract digestibility of N and energy throughout the
      experiment. The inclusion of PC or FC did not affect the blood characteristics
      (p>0.05). Moreover, dietary FC treatment led to a higher (p<0.05) lactobacillus
      concentration and lower E. coli concentration than the NC treatment, whereas the
      antibiotic supplementation only decreased the E. coli concentration. Pigs fed FC
      or PC diet had reduced (p<0.05) fecal NH3 and H2S content compared with those fed
      NC diet. In conclusion, our results indicated that the inclusion of FC01
      treatment could improve the growth performance, nutrient digestibility, fecal
      microbial shedding (lower E. coli and higher lactobacillus), and decrease the
      fecal noxious gas emission in growing pigs when compared with the group fed the
      basal diet. In conclusion, dietary FC could be considered as a good source of
      supplementation in growing pigs because of its growth promoting effect. 

PMID- 25049541
TI  - Prediction of digestible and metabolizable energy content and standardized ileal
      amino Acid digestibility in wheat shorts and red dog for growing pigs.
AB  - Two experiments were conducted to evaluate the effects of chemical composition of
      wheat shorts and red dog on energy and amino acid digestibility in growing pigs
      and to establish prediction models to estimate their digestible (DE) and
      metabolizable (ME) energy content and as well as their standardized ileal
      digestible (SID) amino acid content. For Exp. 1, sixteen diets were fed to thirty
      two growing pigs according to a completely randomized design during three
      successive periods. The basal diet was based on corn and soybean meal while the
      other fifteen diets contained 28.8% wheat shorts (N = 7) or red dog (N = 8),
      added at the expense of corn and soybean meal. Over the three periods, each diet
      was fed to six pigs with each diet being fed to two pigs during each period. The
      apparent total tract digestibility (ATTD) of energy in wheat shorts and red dog
      averaged 75.1 and 87.9%. The DE values of wheat shorts and red dog averaged 13.8
      MJ/kg (range 13.1 to 15.0 MJ/kg) and 15.1 MJ/kg (range 13.3 to 16.6 MJ/kg) of dry
      matter, respectively. For Exp. 2, twelve growing pigs were allotted to two 6*6
      Latin Square Designs with six periods. Ten of the diets were formulated based on
      60% wheat shorts or red dog and the remaining two diets were nitrogen-free diets
      based on cornstarch and sucrose. Chromic oxide (0.3%) was used as an indigestible
      marker in all diets. There were no differences (p>0.05) in SID values for the
      amino acids in wheat shorts and red dog except for lysine and methionine.
      Apparent ileal digestibility (AID) and SID values for lysine in different sources
      of wheat shorts or red dog, which averaged 78.1 and 87.8%, showed more variation
      than either methionine or tryptophan. A stepwise regression was performed to
      establish DE, ME and amino acid digestibility prediction models. Data indicated
      that fiber content and amino acid concentrations were good indicators to predict
      energy values and amino acid digestibility, respectively. The present study
      confirms the large variation in the energy content and amino acid digestibility
      in wheat shorts and red dog, and describes the factors that influence this
      variation and presents equations based on chemical composition that could
      probably be used to predict the DE and ME values as well as the amino acid
      digestibility of wheat shorts and red dog. 

PMID- 25049543
TI  - Methane and nitrous oxide emissions from livestock agriculture in 16 local
      administrative districts of Korea.
AB  - This study was conducted to evaluate methane (CH4) and nitrous oxide (N2O)
      emissions from livestock agriculture in 16 local administrative districts of
      Korea from 1990 to 2030. National Inventory Report used 3 yr averaged livestock
      population but this study used 1 yr livestock population to find yearly emission
      fluctuations. Extrapolation of the livestock population from 1990 to 2009 was
      used to forecast future livestock population from 2010 to 2030. Past (yr 1990 to
      2009) and forecasted (yr 2010 to 2030) averaged enteric CH4 emissions and CH4 and
      N2O emissions from manure treatment were estimated. In the section of enteric
      fermentation, forecasted average CH4 emissions from 16 local administrative
      districts were estimated to increase by 4%-114% compared to that of the past
      except for Daejeon (-63%), Seoul (-36%) and Gyeonggi (-7%). As for manure
      treatment, forecasted average CH4 emissions from the 16 local administrative
      districts were estimated to increase by 3%-124% compared to past average except
      for Daejeon (-77%), Busan (-60%), Gwangju (-48%) and Seoul (-8%). For manure
      treatment, forecasted average N2O emissions from the 16 local administrative
      districts were estimated to increase by 10%-153% compared to past average CH4
      emissions except for Daejeon (-60%), Seoul (-4.0%), and Gwangju (-0.2%). With the
      carbon dioxide equivalent emissions (CO2-Eq), forecasted average CO2-Eq from the
      16 local administrative districts were estimated to increase by 31%-120% compared
      to past average CH4 emissions except Daejeon (-65%), Seoul (-24%), Busan (-18%),
      Gwangju (-8%) and Gyeonggi (-1%). The decreased CO2-Eq from 5 local
      administrative districts was only 34 kt, which was insignificantly small compared
      to increase of 2,809 kt from other 11 local administrative districts. Annual
      growth rates of enteric CH4 emissions, CH4 and N2O emissions from manure
      management in Korea from 1990 to 2009 were 1.7%, 2.6%, and 3.2%, respectively.
      The annual growth rate of total CO2-Eq was 2.2%. Efforts by the local
      administrative offices to improve the accuracy of activity data are essential to
      improve GHG inventories. Direct measurements of GHG emissions from enteric
      fermentation and manure treatment systems will further enhance the accuracy of
      the GHG data. (Key Words: Greenhouse Gas, Methane, Nitrous Oxide, Carbon Dioxide
      Equivalent Emission, Climate Change). 

PMID- 25049542
TI  - Effects of Dietary Fat Types on Growth Performance, Pork Quality, and Gene
      Expression in Growing-finishing Pigs.
AB  - This study was performed to determine the effects of dietary fat sources, i.e.,
      beef tallow, soybean oil, olive oil and coconut oil (each 3% in feed), on the
      growth performance, meat quality and gene expression in growing-finishing pigs. A
      total of 72 crossbred pigs (Landrace*Large White*Duroc) were used at 71+/-1 kg
      body weight (about 130 d of age) in 24 pens (320*150 cm) in a confined pig house
      (three pigs per pen) with six replicate pens per treatment. The growing diet was
      given for periods of 14+/-3 d and the finishing diet was given for periods of
      28+/-3 d. The fat type had no significant effect either on growth performance or
      on chemical composition or on meat quality in growing-finishing pigs. Dietary fat
      type affected fatty acid composition, with higher levels of unsaturated fatty
      acids (UFAs) and monounsaturated fatty acids (MUFAs) in the olive oil group.
      Microarray analysis in the Longissimus dorsi identified 6 genes, related to
      insulin signaling pathway, that were differentially expressed among the different
      feed groups. Real time-PCR was conducted on the six genes in the longissimus
      dorsi muscle (LM). In particular, the genes encoding the protein kinase, cAMP
      dependent, regulatory, type II, alpha (PRKAR2A) and the catalytic subunit of
      protein phosphatase 1, beta isoform (PPP1CB) showed the highest expression level
      in the olive oil group (respectively, p<0.05, p<0.001). The results of this study
      indicate that the type of dietary fat affects fatty acid composition and insulin
      signaling-related gene expression in the LM of pigs. 

PMID- 25049544
TI  - Colour Changes in Meat of Foals as Affected by Slaughtering Age and Post-thawing
      Time.
AB  - The aim of the present work was to investigate how colour changes of foal meat
      can vary after thawing out in relation to the slaughtering age of the horses and
      to the post-thawing time. Eighteen Italian Heavy Draught Horse (IHDH) foals were
      used for the trial. They were subdivided in three groups according to their
      slaughtering age (6, 11 and 18 months). Two different surfaces were investigated
      for each sample: a fresh cut surface (daily renewed cutting surface: DRCS), and
      not-renewed cutting surface (NRCS). The redness of both investigated surfaces
      increased with slaughtering age (p<0.01). Moreover, this parameter decreased
      during post-thawing time (p<0.01) only on the NRCS, probably due to the myoglobin
      oxidation processes. Colour is an important visual cue denoting perceived quality
      by consumers. So, by a chromatic perspective the thawed meat of IHDH foals
      slaughtered at 6 and 11 months proved to be that which best meets the market
      requirements. 

PMID- 25049545
TI  - Estimation of weaning age effects on growth performance in berkshire pigs.
AB  - Analysis for back fat thickness (BFAT) and daily body weight gains from birth to
      the end of a performance test were conducted to find an optimal method for
      estimation of weaning age effects and to ascertain impacts of weaning age on the
      growth performance of purebred Berkshire pigs from a closed population in Korea.
      Individual body weights were measured at birth (B), at weaning (W: mean, 22.9 d),
      at the beginning of the performance test (P: mean, 72.7 d), and at the end of the
      performance test (T: mean, 152.4 d). Further, the average daily gains in body
      weight (ADG) of 3,713 pigs were analyzed for the following periods: B to W
      (DGBW), W to P (DGWP), P to T (DGPT), B to P (DGBP), B to T (DGBT), and W to T
      (DGWT). Weaning ages ranged from 17 to 34 d, and were treated as fixed (WF),
      random with (WC) and random without (WU) consideration of an empirical
      relationship between weaning ages in the models. WF and WC produced the lowest
      AIC (Akaike Information Criterion) and least fractions of error variance
      components in multi-traits analysis, respectively. The fractions of variances due
      to diverse weaning age and the weaning age correlations among ADGs of different
      stages (when no overlapping allowed) by WC ranged from 0.09 to 0.35 and from 
      0.03 to 0.44, respectively. The maximum weaning age effects and optimal back fat
      thicknesses were attained at weaning ages of 27 to 32 d. With the exception of
      DGBW, the effects of weaning age on the ADGs increased (ranging from 1.50 g/d to
      7.14 g/d) with increased weaning age. In addition, BFAT was reduced by 0.106 mm
      per increased day in weaning age. In conclusion, WC produced reasonable weaning
      age correlations, and improved the fitness of the model. Weaning age was one of
      crucial factors (comparable with heritability) influencing growth performance in
      Berkshire pigs. Further, these studies suggest that increasing weaning age up to
      32 d can be an effective management strategy to improve growth performance.
      However, additional investigations of the costs and losses related to extension
      of the suckling period and on the extended range of weaning age are necessary to
      determine the productivity and safety of this practice in a commercial herd and
      production system. 

PMID- 25049546
TI  - Tissues Expression, Polymorphisms of IFN Regulatory Factor 6 (IRF6) Gene and
      Their Associated with Immune Traits in Three Pig Populations.
AB  - Interferon regulatory factor 6 (IRF6) gene is a member of the IRF-family, and
      plays functionally diverse roles in the regulation of the immune system. In this
      report, the 13,720 bp porcine IRF6 genomic DNA structure was firstly identified
      with a putative IRF6 protein of 467 amino acids. Alignment and phylogenetic
      analysis of the porcine IRF6 amino acid sequences with their homologies to other
      species showed high identity (over 96%). Tissues expression of IRF6 mRNA was
      observed by RT-PCR, the results revealed IRF6 expressed widely in eight tissues.
      One SNP (HQ026023:1383 G>C) in exon7 and two SNPs (HQ026023:130 G>A; 232 C>T) in
      the 5 ' promoter region of porcine IRF6 gene were demonstrated b y DNA sequencing
      analysis. A further analysis of SNP genotypes associated with immune traits
      including IFN-gamma and IL10 concentrations in serum was carried out in three pig
      populations including Large White, Landraces and Songliao Black pig (a Chinese
      indigenous breed). The results showed that the SNP (HQ026023:1383 G>C) was
      significantly associated with the level of IFN-gamma (d 20) in serum (p = 0.038)
      and the ratio of IFN-gamma to IL10 (d 20) in serum (p = 0.041); The other two
      SNPs (HQ026023:130 G>A; 232 C>T) were highly significantly associated with IL10
      level in serum both at the day 20 (p = 0.005; p = 0.001) and the day 35 (p =
      0.004; p = 0.006). Identification of the porcine IRF6 gene will help our further
      understanding of the molecular basis of the IFN regulation pathway in the porcine
      immune response. All these results should indicate that the IRF6 gene can be
      regarded as a molecular marker associated with the IL10 level in serum and used
      for genetic selection in the pig breeding. 

PMID- 25049547
TI  - Shallow Population Genetic Structures of Thread-sail Filefish (Stephanolepis
      cirrhifer) Populations from Korean Coastal Waters.
AB  - Genetic diversities, population genetic structures and demographic histories of
      the thread-sail filefish Stephanolepis cirrhifer were investigated by nucleotide
      sequencing of 336 base pairs of the mitochondrial DNA (mtDNA) control region in
      111 individuals collected from six populations in Korean coastal waters. A total
      of 70 haplotypes were defined by 58 variable nucleotide sites. The neighbor
      joining tree of the 70 haplotypes was shallow and did not provide evidence of
      geographical associations. Expansion of S. cirrhifer populations began
      approximate 51,000 to 102,000 years before present, correlating with the period
      of sea level rise since the late Pleistocene glacial maximum. High levels of
      haplotype diversities (0.974+/-0.029 to 1.000+/-0.076) and nucleotide diversities
      (0.014 to 0.019), and low levels of genetic differentiation among populations
      inferred from pairwise population F ST values (-0.007 to 0.107), support an
      expansion of the S. cirrhifer population. Hierarchical analysis of molecular
      variance (AMOVA) revealed weak but significant genetic structures among three
      groups (F CT = 0.028, p<0.05), and no genetic variation within groups (0.53%; F
      SC = 0.005, p = 0.23). These results may help establish appropriate fishery
      management strategies for stocks of S. cirrhifer and related species. 

PMID- 25049548
TI  - Genetic differentiation of chinese indigenous meat goats ascertained using
      microsatellite information.
AB  - To investigate the genetic diversity of seven Chinese indigenous meat goat breeds
      (Tibet goat, Guizhou white goat, Shannan white goat, Yichang white goat, Matou
      goat, Changjiangsanjiaozhou white goat and Anhui white goat), explain their
      genetic relationship and assess their integrity and degree of admixture, 302
      individuals from these breeds and 42 Boer goats introduced from Africa as
      reference samples were genotyped for 11 microsatellite markers. Results indicated
      that the genetic diversity of Chinese indigenous meat goats was rich. The mean
      heterozygosity and the mean allelic richness (AR) for the 8 goat breeds varied
      from 0.697 to 0.738 and 6.21 to 7.35, respectively. Structure analysis showed
      that Tibet goat breed was genetically distinct and was the first to separate and
      the other Chinese goats were then divided into two sub-clusters: Shannan white
      goat and Yichang white goat in one cluster; and Guizhou white goat, Matou goat,
      Changjiangsanjiaozhou white goat and Anhui white goat in the other cluster. This
      grouping pattern was further supported by clustering analysis and Principal
      component analysis. These results may provide a scientific basis for the
      characteristization, conservation and utilization of Chinese meat goats. 

PMID- 25049549
TI  - Study on the Prolactin Receptor 3 (PRLR3) Gene and the Retinol-binding Protein 4
      (RBP4) Gene as Candidate Genes for Production Traits in Berkshire Pigs.
AB  - To investigate the influence of the prolactin receptor 3 (PRLR3) gene and the
      retinol-binding protein 4 (RBP4) gene on the production traits of swine,
      genotyping was performed on 156 and 141 Berkshire pigs, respectively, that were
      carefully selected for economic traits. The frequencies of allele A in the PRLR3
      locus and allele B in the RBP4 locus were 0.50 and 0.42, respectively. Neither
      locus was in the Hardy-Weinberg equilibrium. After a genotype was assigned to the
      individuals whose parents had the homozygous genotype, a statistical analysis was
      conducted for 291 pigs. The animals with the PRLR3 and RBP4 genotypes included
      182 and 227 head, respectively. Even though the genotypic effects of PRLR3
      (p<0.05) and RBP4 (p<0.01) had a significant influence on the pigs' back fat
      thickness, the interaction of both genes was not highly significant in terms of
      the back fat thickness (p = 0.1235). While the estimated epistasis effects of
      aaBB and aaBb decreased the back fat thickness and reduced the growth rate, the
      effects of AAbb and aabb increased the growth rate. Despite the insignificant
      difference in the PRLR genotypes in terms of the days to 90 kg and the average
      daily gain, the back fat thickness showed a significant difference (p<0.05), and
      the additive effect of allele A and the dominant effect of the hetero-genotype
      were -0.377 and 1.206 mm, respectively. The RBP4 genotypes had a very significant
      effect (p<0.01) on the back fat thickness, the days to 90 kg, and the average
      daily gain. The additive effects of allele B of the RBP4 locus on the back fat
      thickness, the days to 90 kg, and the average daily gain were 0.70 mm, -1.3 days
      and 6.2 g, respectively. Moreover, the dominant effects of the heterozygote for
      those traits were 0.63 mm, 9.9 days and -45.0 g, respectively. Allele A of the
      PRLR3 locus favorably influenced the back fat thickness, the days to 90 kg of the
      body weight, and the average daily gain and its dominant effect unfavorably
      influenced those traits. Allele B of RBP4 showed an incremental growth rate and
      back fat thickness, which could lower the lean meat percentage in the carcass.
      The RBP4 hetero-genotype negatively affected the pork production. These results
      strongly imply that the selection of allele A of PRLR3 and allele B of RBP4 would
      produce highly productive pigs in the Berkshire breed. Careful selection of
      allele B of RBP4 is required because of the increase in the back fat thickness. 

PMID- 25049550
TI  - Seasonal Changes in Serum Testosterone, LDH Concentration and Semen
      Characteristics in Markhoz Goats.
AB  - This experiment was conducted to study variations of serum testosterone and
      seminal characteristics of Markhoz male goats. Blood samples were obtained via
      jugular vein, and semen was collected by using an artificial vagina from 14
      fertile male goats (2-3 years of age), at 15-day intervals starting on 15 July
      and ending on 30 October 2010 (during breeding and non-breeding season). Semen
      volume, total sperm (volume*concentration), live sperm (%), abnormal sperm (%)
      and semen pH were significantly superior during the late summer and early autumn
      (breeding season). Variation of sperm density, motility and progressive motility
      was not significant during the sampling period. The results presented show that
      the lowest and highest levels of lactate dehydrogenase in the seminal plasma were
      recorded in late October (2.82 U/ml) and in late August (4.81 U/ml),
      respectively. Moreover, the study indicated that the serum testosterone
      concentration was higher during late summer and early autumn (p<0.05) than at any
      other of sampling period. There were negative correlations between volume and
      sperm density (-0.135, p<0.05), and positive correlations between volume and
      percentage live sperm (0.224) and percentage progressive motility (0.194,
      p<0.01). Sperm density was correlated with live sperm (0.200, p<0.05) and
      progressive motility (0.202, p<0.01). The correlation between live sperm and
      progressive motility was 0.554 (p<0.01). Furthermore, the results in this study
      indicated a significant positive correlation between live sperm and LDH (0.450)
      and a negative correlation between sperm density and LDH concentration (-0.272)
      (p<0.01). Significant, but positive correlations were found between sperm
      motility and LDH (0.542) and testosterone concentration (0.522), respectively
      (p<0.05). In conclusion, this study demonstrated that the best obtained semen was
      collected in late summer (during decreasing photoperiod) and early autumn
      (September and October). This also coincides with the natural breeding season of
      Markhoz goats in Iran. 

PMID- 25049551
TI  - The relationship of pulmonary artery copper concentrations and genes involved in
      copper homeostasis in cattle, Swine, and goats.
AB  - Liver and pulmonary artery tissue from 5 Angus cross bred steers, 6 goats, and 6
      pigs were collected at a commercial abattoir to examine the relationship of
      pulmonary artery copper (Cu) concentrations and genes involved in copper
      homeostasis. Liver and pulmonary artery samples were collected at the time of
      harvest and snap frozen. Liver and pulmonary artery Cu concentrations were
      determined via flame atomic absorption spectrophotometry and gene expression was
      determined via real time PCR. Liver Cu concentrations (mg Cu/kg DM+/-SE) were
      higher (p<0.01) in cows (396.4+/-109.1) and goats (181.4+/-37.0) than in pigs
      (19.2+/-3.5). All liver Cu concentrations were within normal ranges and
      considered adequate for each species. Liver Cu concentration was more variable in
      cows and goats compared to pig liver Cu concentrations. Pulmonary artery beta
      hydroxylproline was higher (p<0.01) in cow and pig than goat. Real Time PCR
      revealed that goat liver atp7a was positively correlated (r(2) = 0.92; p<0.01) to
      liver Cu concentrations while cow and pig atp7a was not correlated to liver Cu
      concentration. In the pig, liver atp7a concentration was positively correlated to
      atp7b (r(2) = 0.66; p<0.05). Pulmonary artery Cu concentration was highest in
      cows (14.9+/-4.7), intermediate in pigs (8.9+/-3.3), and lowest in goats (3.9+/
      1.1). Goat pulmonary artery Cu concentration was not correlated to ctr1
      concentration, however, atp7a concentration was positively correlated with ctr1
      (r(2) = 0.90; p<0.01). In cow pulmonary artery, loxl1 concentration was
      positively correlated to eln mRNA concentration (r(2) = 0.91; p<0.02). Pulmonary
      artery CTR1 protein concentration was positively correlated to pulmonary artery
      Cu (r(2) = 0.85; p = 0.03) concentration while negatively correlated to liver Cu
      (r(2) = -0.79; p<0.04). Pulmonary artery Cu concentration was not correlated to
      concentration of Cu homeostatic genes in the pig. These data indicate that genes
      involved in Cu homeostasis (ctr1, atp7A, atp7B, loxl1 and eln) are differently
      regulated in different species. 

PMID- 25049552
TI  - Physiological changes in jeju crossbred riding horses by swim training.
AB  - The changes in physiologic parameters by swim exercise duration were examined in
      five female well-trained Jeju crossbred riding horses that had riding experience
      of more than three years without swim training experience. The horses were
      performed with swim exercise for 10 min (60.0 m/min) once a day for 14 days.
      Physiologic characteristics and haematic parameters were measured before
      swimming, immediately after swimming, and after a 10 min rest at first day (D0),
      7 days (D7), and 14 days (D14) of training. After 14 days of swim training, heart
      rate (p<0.05), blood glucose (p<0.05), lactate concentration (p<0.001), packed
      cell volume (p<0.01), and hemoglobin (p<0.01) measured immediately after swim and
      after 10 min rest showed significant lower values than those of D0. The results
      illustrate the benefits of swim training for riding horses and the need for the
      establishment of swimming routines of appropriate duration and intensity to
      maximize the advantages of swim training. 

PMID- 25049553
TI  - Contribution of urine and dung patches from grazing sheep to methane and carbon
      dioxide fluxes in an inner mongolian desert grassland.
AB  - The effects of sheep urine and dung patches on methane (CH4) and carbon dioxide
      (CO2) fluxes were investigated during the summer-autumn in 2010, to evaluate
      their contribution to climate change in a desert grassland in Inner Mongolia,
      China. Results indicate that the cumulative CH4 emissions for dung patches, urine
      patches and control plots were - -0.076, -0.084, and -0.114 g/m(2) and these were
      net CH4 sinks during the measured period. The level of CH4 intake from urine and
      dung plots decreased 25.7%, and 33.3%, respectively, compared with a control
      plot. CO2 fluxes differed (p<0.01) in urine plots, with an average of 569.20
      mg/m(2)/h compared with control plots (357.62 mg/m(2)/h) across all sampling
      days. Dung patches have cumulative CO2 emissions that were 15.9% higher compared
      with the control during the 55-d period. Overall, sheep excrement weakened CH4
      intake and increased CO2 emissions. 

PMID- 25049554
TI  - Effect of Total Mixed Ration with Fermented Feed on Ruminal In vitro
      Fermentation, Growth Performance and Blood Characteristics of Hanwoo Steers.
AB  - In this study, two experiments were conducted to evaluate the total mixed ration
      with fermented feed (TMRF) and total mixed ration (TMR) by rumen in vitro
      fermentation and their effects on the growth performance and blood
      characteristics of Hanwoo steers. In experiment 1, three Hanwoo steers (600+/-47
      kg), each permanently fitted with a ruminal cannula were used. In this
      experiment, three diets designated as T1, TMRF (18.4% fermented feed, tall
      fescue, mammoth wild rye forage and whole crop barley); T2, TMRF (17.7% fermented
      feed, rice straw and whole crop barley); and T3, TMR (rice straw, whole crop
      barley and probiotics, but no fermented feed), which were subjected to rumen in
      vitro fermentation for 48 h. The results demonstrated that DM disappearance rate
      gradually increased with advancing fermentation time, but T1 and T2 were higher
      than the T3 (p<0.05) from 3 h to 12 h, but insignificant (p>0.05) at 24 and 48 h.
      None of the specific VFAs were affected except for acetic and non volatile lactic
      acids, which were produced more in T2 than in T1 and T3 at 24 h and 48 h of
      incubation. A/P was lower in T1 and T2 than inT3 at 24 h (p<0.05) and 48 h
      (p>0.05) of incubation. These results confirmed that TMRF-related treatment shows
      a superior performance to that of TMR during the ruminal fermentation period. In
      experiment 2, the three diets in experiment 1 plus 1 more control diet
      (concentrates, probiotics and 2% rice straw of body weight) were fed to the 48
      Hanwoo steers (160+/-10 kg) for a period of 168 d. The results demonstrated that
      the daily and total live weight gain and feed efficiency were higher (p<0.05) in
      the TMRF and TMR groups than in the control group. SGOT, SGPT and BUN (p<0.05)
      were reduced in TMRF relative to the control and TMR groups by 168 d which
      confirmed that TMRF shows better blood profiles than the TMR and control groups.
      Overall, these results appear to show that TMRF has better in vitro ruminal
      characteristics than those of TMR; growth performance and blood profiles were
      also found to be superior in TMRF than in the TMR and control groups. Thus, our
      findings suggest that TMRF-based feed supplies are favorable for Hanwoo cattle. 

PMID- 25049555
TI  - The limiting sequence and proper ratio of lysine, methionine and threonine for
      calves fed milk replacers containing soy protein.
AB  - The limiting sequence and relative ratio of lysine (Lys), methionine (Met), and
      threonine (Thr) for calves about 2 mo of age fed milk replacers (MR) containing
      soy protein are not clearly defined. The objective of the study was to
      investigate the effect of supplementing MR containing 22% CP, half from soy
      protein concentrate (SPC, 40.56% CP, flour) and half from whey proteins, with
      Lys, Met, and Thr to estimate amino acid (AA) sequence and their relative ratio
      for calves about 2 mo of age. A method of partial deduction of AA was adopted.
      Twenty-four newborn calves (half males and half females, 40.7+/-0.9 kg of BW)
      were fed 1 of 4 MR diets for 56 d (n = 6/diet). The diets were supplemented with
      all (positive control) or with 2 of the 3 AAs: Lys, Met and Thr, (i.e., PC (22%
      CP, 2.34% Lys, 0.72% Met and 1.80% Thr), PC-Lys (22% CP, 1.64% Lys, 0.72% Met and
      1.80% Thr), PC-Met (22% CP, 2.34% Lys, 0.50% Met and 1.80% Thr), and PC-Thr (22%
      CP, 2.34% Lys, 0.72% Met and 1.26% Thr)). Calves were fed thrice daily; starter
      (20% CP, 1.03% Lys, 0.30% Met and 0.69% Thr), hay (3.23% CP, 0.29% Lys, 0.12% Met
      and 0.23% Thr) and water were offered free choice. Starter and hay were only
      offered beginning on d 36 (after 5 wk) and d 43 (after 6 wk), respectively. BW,
      body size and blood samples measures were taken every two weeks. Three-day total
      collection of feed refusals, feces, and urine were recorded starting at d 33 and
      d 54 of age, respectively. From the results, the limiting sequence and relative
      ratio between the 3 AAs in calves with different diet structures were calculated.
      The limiting sequence of the 3 AAs were ranked as Lys, Met and Thr; the proper
      ratio was 100:29:70 for MR-only diet and 100:30:60 for diets consisted of MR,
      starter and hay. Nitrogen digestion and utilization and nutrient digestibility
      were negatively affected by AA deletion treatments. From the evidence of this
      experiment, it did not appear that the AA limiting sequence was selectively
      altered by differences in diet structures such as would be encountered in
      practice. The relative ratio between the 3 AAs varied with the offer of starter
      and hay to calves, and the average ratio was 100:29.5:65 for calves during 2 to
      10 wk of age. 

PMID- 25049556
TI  - The Effect of Forage Level and Oil Supplement on Butyrivibrio fibrisolvens and
      Anaerovibrio lipolytica in Continuous Culture Fermenters.
AB  - The objective of this study was to evaluate the effects of forage level and oil
      supplement on selected strains of rumen bacteria believed to be involved in
      biohydrogenation (BH). A continuous culture system consisting of four fermenters
      was used in a 4*4 Latin square design with a factorial arrangement of treatments,
      with four 10 d consecutive periods. Treatment diets were: i) high forage diet
      (70:30 forage to concentrate (dry matter basis); HFC), ii) high forage plus oil
      supplement (HFO), iii) low forage diet (30:70 forage to concentrate; LFC), and
      iv) low forage plus oil supplement (LFO). The oil supplement was a blend of fish
      oil and soybean oil added at 1 and 2 g/100 g dry matter, respectively. Treatment
      diets were fed for 10 days and samples were collected from each fermenter on the
      last day of each period 3 h post morning feeding. The concentrations of vaccenic
      acid (t11C18:1; VA) and c9t11 conjugated linoleic acid (CLA) were greater with
      the high forage diet while the concentrations of t10 C18:1 and t10c12 CLA were
      greater with the low forage diet and addition of oil supplement increased their
      concentrations at both forage levels. The DNA abundance of Anaerovibrio
      lipolytica, and Butyrivibrio fibrisolvens vaccenic acid subgroup (Butyrivibrio
      VA) were lower with the low forage diets but not affected by oil supplement. The
      DNA abundance of Butyrivibrio fibrisolvens stearic acid producer subgroup
      (Butyrivibrio SA) was not affected by forage level or oil supplement. In
      conclusion, oil supplement had no effects on the tested rumen bacteria and forage
      level affected Anaerovibrio lipolytica and Butyrivibrio VA. 

PMID- 25049557
TI  - Metabolisable Energy, In situ Rumen Degradation and In vitro Fermentation
      Characteristics of Linted Cottonseed Hulls, Delinted Cottonseed Hulls and
      Cottonseed Linter Residue.
AB  - Dietary supplementation with conventional linted cottonseed hulls (LCSH) is a
      common practice in livestock production all over the world. However,
      supplementation with mechanically delinted cottonseed hulls (DCSH) and cottonseed
      linter residue (CLR) is uncommon. Cottonseed by-products, including LCSH, DCSH
      and CLR, were assessed by chemical analysis, an in situ nylon bag technique, an
      in vitro cumulative gas production technique and in vitro enzyme procedure. The
      crude protein (CP) content of CLR (302 g/kg dry matter (DM)) was approximately 3
      times that of LCSH and 5 times that of DCSH. The crude fat content was
      approximately 3 times higher in CLR (269 g/kg DM) than in LCSH and 4 times higher
      than in DCSH. Neutral detergent fibre (311 g/kg DM) and acid detergent fibre (243
      g/kg DM) contents of CLR were less than half those of DCSH or LCSH. Metabolisable
      energy, estimated by in vitro gas production and chemical analyses, ranked as
      follows: CLR (12.69 kJ/kg DM)>LCSH (7.32 kJ/kg DM)>DCSH (5.82 kJ/kg DM). The in
      situ degradation trial showed that the highest values of effective degradability
      of DM and CP were obtained for CLR (p<0.05). The in vitro disappearance of
      ruminal DM ranked as follows: CLR>LCSH>DCSH (p<0.05). The lowest digestibility
      was observed for DCSH with a two-step in vitro digestion procedure (p<0.05). The
      potential gas production in the batch cultures did not differ for any of the
      three cottonseed by-product feeds. The highest concentration of total volatile
      fatty acids was observed in CLR after a 72 h incubation (p<0.05). The molar
      portions of methane were similar between all three treatments, with an average
      gas production of 22% (molar). The CLR contained a higher level of CP than did
      LCSH and DCSH, and CLR fermentation produced more propionate. The DCSH and LCSH
      had more NDF and ADF, which fermented into greater amounts of acetate. 

PMID- 25049558
TI  - Effects of boron supplementation to diets deficient in calcium and phosphorus on
      performance with some serum, bone and fecal characteristics of broiler chickens.
AB  - Three levels of boron (0, 30, 60 ppm) were supplemented in practical corn-soybean
      based starter and grower diets, containing either adequate or inadequate Ca or P.
      A total of 1,800, 1-day-old sexed broiler chicks were assigned to six dietary
      treatments and fed with the experimental diets for 42 days. Boron improved the
      overall feed conversion ratio, but increased body weight only at 21 days of age
      (p<0.01). Boron decreased feed intake in the case of feeding on a diet deficient
      in Ca and P, and tended to increase feed intake when birds received a diet
      adequate in Ca and P, signifying significant boron by Ca-P interaction (p<0.01).
      Mortality was not influenced by boron (p>0.05). Dietary Ca and P deprivation
      reduced body weight and feed consumption significantly, but did not influence the
      feed conversion ratio and mortality (p>0.05). Serum Ca level, ALP and ALT
      activities were not influenced either by dietary Ca and P deficiency or boron
      supplementation. Serum P content increased with respect to boron at 30 ppm. Bone
      breakage strength was not affected by dietary variables. Tibia ash, Ca and P were
      increased in response to the supplementation diet with 30 ppm boron, whereas 60
      ppm showed no effect in most cases. Accordingly, the dietary boron
      supplementation of 30 ppm significantly decreased fecal Ca and P excretion, while
      there was a numerical decline in the 60 ppm boron as compared to the 0 ppm boron
      group. Data presented herein indicated that boron, either at the 30 ppm or 60 ppm
      supplementation level, was effective in conversion of feed to body weight,
      whereas only boron at 30 ppm contributed to the mineralization of bone thereby
      augmenting more Ca and P while excreting less through faeces. 

PMID- 25049559
TI  - Immune Response of Broiler Chickens Fed Diets Supplemented with Different Level
      of Chromium Methionine under Heat Stress Conditions.
AB  - The objectives of this study were to investigate the immune responses of broiler
      chickens fed diets supplemented with different level of chromium methionine
      (CrMet) in heat stress (HS) condition. Two hundred and eighty eight male broiler
      chickens (Ross 308) were allocated to four treatment groups (supplementation with
      0, 200, 400 or 800 ppb Cr in the form of CrMet) in a completely randomized
      design. The experiment was conducted at heat stressed condition and all birds
      were kept under temperature of 33+/-2 degrees C. Antibody titers against
      Newcastle disease virus (NDV) and infectious bronchitis virus (IBV), heterophil
      to lymphocyte ratios (H/L), and concentration of plasma cortisol (CPC) were
      measured at 21 and 42 d. At 42 days of age two birds were chosen randomly from
      each replicate, slaughtered, spleen and bursa of Fabricius were collected,
      weighed and expressed as a percentage of live body weight. Antibody titers
      against NDV and IBV at 21 and 42 days of age in broiler fed supplemental CrMet
      were higher than in broiler chickens fed control diet (p<0.05). CPC level in
      broiler chickens fed CrMet were significantly (p<0.05) decreased. Increases in
      lymphocyte counts and consequently a decrease in heterophil to lymphocyte ratios
      in broiler chickens fed 800 ppb Cr were observed at 21 and 42 d. Supplementation
      with CrMet had no significant effect on lymphoid organs of broilers. The results
      suggest that dietary CrMet supplementation at a level of 800 ppb can improve some
      immune responses of broiler chickens under heat stress conditions. 

PMID- 25049560
TI  - The Dietary Effects of Fermented Chlorella vulgaris (CBT((r))) on Production
      Performance, Liver Lipids and Intestinal Microflora in Laying Hens.
AB  - Fermented Chlorella vulgaris CBT((r)) was evaluated for its effects on egg
      production, egg quality, liver lipids and intestinal microflora in laying hens.
      One hundred and eight Hy-line Brown layers (n = 108), 80 wk of age, were fed a
      basal diet supplemented with CBT((r)) at the level of 0, 1,000 or 2,000 mg/kg,
      respectively for 42 d. Egg production was measured daily and egg quality was
      measured every two weeks. Five eggs from each replicate were collected randomly
      to determine egg quality. Egg production increased linearly with increasing
      levels of CBT((r)) supplementation (p<0.05), although there was no significant
      effect of treatment on feed intake. Egg yolk color (p<0.001) and Haugh unit
      (p<0.01) improved linearly with increasing dietary CBT((r)). Hepatic
      triacylglycerol level was linearly decreased with increasing dietary CBT((r))
      (p<0.05). The supplemental CBT((r)) resulted in linear (p<0.001) and quadratic
      (p<0.01) response in population of cecal lactic acid bacteria. In conclusion,
      fermented Chlorella vulgaris supplemented to laying hen diets improved egg
      production, egg yolk color, Haugh unit and positively affected the contents of
      hepatic triacylglycerol and the profiles of cecal microflora. 

PMID- 25049561
TI  - One Alpha-hydroxycholecalciferol Improves Growth Performance, Tibia Quality, and
      Meat Color of Broilers Fed Calcium- and Phosphorus-Deficient Diets.
AB  - An experiment was conducted to evaluate the effects of one alpha
      hydroxycholecalciferol (1alpha-OH D3) on growth performance, tibia quality, and
      skin and meat color in broilers fed calcium (Ca)- and phosphorus (P)-deficient
      corn-soybean meal diets. A total of 288 male Ross broilers, at 21 days of age,
      were randomly assigned to three treatments with eight cages per treatment. Three
      levels of 1alpha-OH D3 (0, 5, and 10 MUg/kg) were added to a basal diet (0.50%
      Ca, 0.13% non-phytate phosphorus (NPP), and 0.35% total phosphorus (tP)) without
      vitamin D3. As a result of this study, the addition of 1alpha-OH D3 increased
      body weight gain (p<0.001), feed intake (p = 0.007), feed efficiency (p<0.001),
      tibia weight (p = 0.002), length (p<0.001), breaking-strength (p = 0.012), ash
      (p<0.001), Ca (p<0.001), and P content (p = 0.004). Dietary 1alpha-OH D3 enhanced
      breast meat yellowness (p = 0.015) and the length and weight of the small
      intestine of the broilers. Moreover, 1alpha-OH D3 decreased serum Ca
      concentration (p = 0.074) and breast meat redness (p = 0.010). These results
      indicate that the 1alpha-OH D3 improves growth, tibia quality, and meat color in
      broilers fed Ca- and P-deficient corn-soybean meal diets. 

PMID- 25049562
TI  - Compensatory Growth of Grower Olive Flounder (Paralichthys olivaceus) with
      Different Feeding Regime at Suboptimal Temperature.
AB  - Compensatory growth of grower olive flounder (Paralichthys olivaceus) was
      determined at suboptimal temperature (13.0+/-1.9 degrees C). Fifteen fish
      averaging 201.1 g per tank were distributed into 18 of 300 L flow-through tanks.
      Six treatments were prepared in triplicate: fish were hand-fed with an extruded
      pellet to apparent satiation once a day for 16 weeks (16 WF); and the other five
      groups of fish were hand-fed for 15, 14, 13, 12 and 10 weeks after 1-, 2-, 3-, 4-
      and 6-week feed deprivation, referred to as 15 WF, 14 WF, 13 WF, 12 WF and 10 WF,
      respectively. A linear relationship between body weight of fish and feed
      deprivation was observed: Y (Body weight of fish) = -1.81X (Weeks of feed
      deprivation)+201.07, R(2) = 0.83. Weight gain of grower olive flounder in 15 WF,
      14 WF, 13 WF and 12 WF treatments was comparable to that of fish in 16 WF
      treatment, but lower than that of fish in 10 WF treatment. Specific growth rate
      of fish in 15 WF treatment was higher than that of fish in 16 WF, 14 WF and 10 WF
      treatments. Feed consumption of fish was not affected by feeding regime. Feed and
      protein efficiency ratios of fish in 15 WF treatment were higher than those of
      fish in 13 WF, 12 WF and 10 WF treatments. Grower olive flounder could achieve
      full compensatory growth when fish were daily fed for 12 weeks after 4-week feed
      deprivation at suboptimal temperature. 

PMID- 25049563
TI  - Analysis of Gene Expression Responses to a Salmonella Infection in Rugao Chicken
      Intestine Using GeneChips.
AB  - Poultry products are an important source of Salmonella enterica. An effective way
      to reduce food poisoning due to Salmonella would be to breed chickens more
      resistant to infection. Unfortunately host responses to Salmonella are complex
      with many factors involved. To learn more about responses to Salmonella in young
      chickens of 2 wk old, a cDNA Microarray containing 13,319 probes was performed to
      compare gene expression profiles between two chicken groups under control and
      Salmonella infected conditions. Newly hatched chickens were orally infected with
      S. enterica serovar Enteritidis. Since the intestine is one of the important
      barriers the bacteria encounter after oral inoculation, intestine gene expression
      was investigated at 2 wk old. There were 588 differentially expressed genes
      detected, of which 276 were known genes, and of the total number 266 were up
      regulated and 322 were down-regulated. Differences in gene expression between the
      two chicken groups were found in control as well as Salmonella infected
      conditions indicating a difference in the intestine development between the two
      chicken groups which might be linked to the difference in Salmonella
      susceptibility. The differential expressions of 4 genes were confirmed by
      quantitative real-time PCR and the results indicated that the expression changes
      of these genes were generally consistent with the results of GeneChips. The
      findings in this study have lead to the identification of novel genes and
      possible cellular pathways, which are host dependent. 

PMID- 25049564
TI  - Body Weight Changes of Laboratory Animals during Transportation.
AB  - The majority of laboratory animals were transported from commercial breeders to a
      research facility by ground transportation. During the transportation, many
      biological functions and systems can be affected by stress. In this experiment,
      the change of body weight during the transportation was measured and the recovery
      periods from the transportation stress established based on the body weight
      changes. Total 676 laboratory animals which were aged between 3 to 9 wk old were
      studied. The transportation time taken from container packing to unpacking the
      container was approximately 24 h. The temperature of animal container was
      constantly maintained by air-conditioning and heating equipment. Rats were found
      to be more sensitive than mice. The body weight of rats was significantly
      decreased 3.71% (p<0.05) compared to the body weight of mice which decreased 0.9%
      There was no significant difference between the strains in the same species. When
      the changes of body weights were compared between delivery days, C57BL/6 mice
      showed the most variable changes compared to other species and strains.
      Consequently, C57BL/6 was more sensitive to stress than the other strains and the
      transportation process needs to be standardized to reduce between day
      variability. To establish the recovery periods from transportation stress, the
      body weight changes were measured during the acclimation period. Although the
      body weight of animals decreased during transportation, animals recovered their
      weight loss after the next day. 

PMID- 25049565
TI  - Quality of Low Fat Chicken Nuggets: Effect of Sodium Chloride Replacement and
      Added Chickpea (Cicer arietinum L.) Hull Flour.
AB  - While attempting to develop low salt, low fat and high fibre chicken nuggets, the
      effect of partial (40%) common salt substitution and incorporation of chickpea
      hull flour (CHF) at three different levels viz., 5, 7.5 and 10% (Treatments) in
      pre-standardized low fat chicken nuggets (Control) were observed. Common salt
      replacement with salt substitute blend led to a significant decrease in pH,
      emulsion stability, moisture, ash, hardness, cohesiveness, gumminess and
      chewiness values while incorporation of CHF in low salt, low fat products
      resulted in decreased emulsion stability, cooking yield, moisture, protein, ash,
      color values, however dietary fibre and textural properties were increased
      (p<0.01). Lipid profile revealed a decrease in total cholesterol and glycolipid
      contents with the incorporation of CHF (p<0.01). All the sensory attributes
      except appearance and flavor, remained unaffected with salt replacement, while
      addition of CHF resulted in lower sensory scores (p<0.01). Among low salt, low
      fat chicken nuggets with CHF, incorporation CHF at 5% level was found optimum
      having sensory ratings close to very good. Thus most acceptable low salt, low fat
      and high fibre chicken nuggets could be developed by a salt replacement blend and
      addition of 5% CHF. 

PMID- 25049566
TI  - Evaluation of optimum genetic contribution theory to control inbreeding while
      maximizing genetic response.
AB  - Inbreeding is the mating of relatives that produce progeny having more homozygous
      alleles than non-inbred animals. Inbreeding increases numbers of recessive
      alleles, which is often associated with decreased performance known as inbreeding
      depression. The magnitude of inbreeding depression depends on the level of
      inbreeding in the animal. Level of inbreeding is expressed by the inbreeding
      coefficient. One breeding goal in livestock is uniform productivity while
      maintaining acceptable inbreeding levels, especially keeping inbreeding less than
      20%. However, in closed herds without the introduction of new genetic sources
      high levels of inbreeding over time are unavoidable. One method that increases
      selection response and minimizes inbreeding is selection of individuals by
      weighting estimated breeding values with average relationships among individuals.
      Optimum genetic contribution theory (OGC) uses relationships among individuals as
      weighting factors. The algorithm is as follows: i) Identify the individual having
      the best EBV; ii) Calculate average relationships ( [Formula: see text]) between
      selected and candidates; iii) Select the individual having the best EBV adjusted
      for average relationships using the weighting factor k, [Formula: see text]. iv)
      Repeat process until the number of individuals selected equals number required.
      The objective of this study was to compare simulated results based on OGC
      selection under different conditions over 30 generations. Individuals (n = 110)
      were generated for the base population with pseudo random numbers of N~ (0, 3),
      ten were assumed male, and the remainder female. Each male was mated to ten
      females, and every female was assumed to have 5 progeny resulting in 500
      individuals in the following generation. Results showed the OGC algorithm
      effectively controlled inbreeding and maintained consistent increases in
      selection response. Difference in breeding values between selection with OGC
      algorithm and by EBV only was 8%, however, rate of inbreeding was controlled by
      47% after 20 generation. These results indicate that the OGC algorithm can be
      used effectively in long-term selection programs. 

PMID- 25049567
TI  - The Signaling Mechanism of TGF-beta1 Induced Bovine Mammary Epithelial Cell
      Apoptosis.
AB  - The present study showed that Transforming growth factor beta 1 (TGF-beta1) can
      induce apoptosis of bovine mammary epithelial cells. This apoptosis was also
      observed with phosphorylation of Smad2/3 within 0.5-2 h. Afterwards the signal
      transferred into the nucleus. Moreover, intracellular free Ca(2+) concentration
      was significantly elevated as well as Caspase-3 activated and DNA lysised,
      thereby inducing the programmed cell death. This signaling pathway of TGF-beta1
      was blocked by SB-431542 (10(-2) MUM) via inhibiting ALK-5 kinase activity, which
      thus reversed the anti-proliferation and apoptosis effect of TGF-beta1 in mammary
      epithelial cells. These results indicated that TGF-beta1 induced apoptosis of
      bovine mammary epithelial cells through the ALK-5-Smad2/3 pathway, which plays an
      important role in inhibiting survival of mammary epithelial cells. Moreover,
      intracellular Ca(2+) also played a critical role in TGF-beta1-induced cell
      apoptosis. 

PMID- 25049568
TI  - Effect of supplementation of fish and canola oil in the diet on milk Fatty Acid
      composition in early lactating holstein cows.
AB  - This study examined the effects of supplementation of fish oil and canola oil in
      the diet on milk yield, milk components and fatty acid composition of Holstein
      dairy cows in early lactation. Eight multiparous early lactation Holstein cows
      (42+/-12 DIM, 40+/-6 kg daily milk yield) were fed a total mixed ration
      supplemented with either 0% oil (Control), 2% fish oil (FO), 1% canola oil +1%
      fish oil (FOCO), or 2% canola oil (CO) according to a double 4*4 Latin square
      design. Each period lasted 3 wk; experimental analyses were restricted to the
      last week of each period. Supplemental oils were added to a basal diet which was
      formulated according to NRC (2001) and consisted of 20% alfalfa, 20% corn silage
      and 60% concentrate. Milk yield was similar between diets (p>0.05), but dry
      matter intake (DMI) was lower (p<0.05) in cows fed FO diet compared to other
      diets. Milk fat percentage and daily yield decreased (p<0.01) with the
      supplementation of fish and canola oil. The daily yield and percentage of milk
      protein, lactose and solids-not-fat (SNF) were not affected by diets (p>0.05).
      The proportion (g/100 g fatty acids) of short chain fatty acids (SCFA) decreased
      and polyunsaturated fatty acids (PUFA) increased (p<0.05) in milk of all cows fed
      diets supplemented with oil. The proportions of 6:0, 8:0, 10:0 12:0 and 14:0
      fatty acids in milk fat decreased (p<0.01) for all diets supplemented with oil,
      but the proportions of 14:1, 16:0 and 16:1 fatty acids were not affected by diets
      (p>0.05). The proportion of trans(t)-18:1 increased (p<0.01) in milk fat of cows
      fed FO and FOCO diets, but CO diet had the highest proportion of cis(c)-11 18:1
      (p<0.01). The concentration of t-10, c-12 18:2, c-9 t-11 18:2, 18:3,
      eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) increased
      (p<0.05) in FO and FOCO diets in comparison with the other two diets. These data
      indicate that including fish oil in combination with canola oil significantly
      modifies the fatty acid composition of milk. 

PMID- 25049569
TI  - Spent mushroom substrate influences elk (cervus elaphus canadensis) hematological
      and serum biochemical parameters.
AB  - The objective of this study was to evaluate the effect of spent mushroom
      substrate (SMS) derived from Pleurotus eryngii on the hematological and
      biochemical blood properties of elk. A total of 18, two and three-year-old elk
      were fed three different levels of SMS (0, 15 and 20%) in a corn-wheat bran diet
      for 80 days. The results indicated significantly high levels of blood monocytes,
      hemoglobin (Hb), and hematocrit (HCT) in elk fed 15% or 20% SMS (p<0.05) compared
      to control animals. Serum blood urea nitrogen (BUN) and glucose concentrations
      were also significantly elevated in elk fed both 15% and 20% SMS. The inclusion
      of SMS in the elk diet did not affect serum total cholesterol, triglyceride, or
      low density lipoprotein (LDL)-cholesterol concentrations; however, high density
      lipoprotein (HDL)-cholesterol concentration was significantly increased in SMS
      fed groups. In addition, 20% SMS in the diet increased serum iron and
      testosterone concentrations in elk. These results indicate that adding SMS to the
      diet of elk can increase their Hgb, serum BUN, glucose, and HDL-cholesterol
      concentration; therefore, diets containing SMS may enhance the physiologic
      condition of elk during growth. 

PMID- 25049571
TI  - The Influence of Dietary Characteristics on the Milk Quantity and Quality of
      Riverine Buffaloes: Estimate of the Energy/Protein Requirements, for a Medium
      high Production, in the First Ninety Days of Lactation.
AB  - The data used came from two trials undertaken under the same climatic conditions
      (spring-summer). In both trials pluriparious buffaloes were utilized similar in
      weight, body condition score, and milk production from the previous year. From
      the first trial the data used was from the sub-period 23-88 DIM provided by seven
      animals fed ad libitum with diet A (6.69 MJ/kg DM; 158.30 g/kg of crude protein)
      with a forage/concentrate ratio of 48/52. From the second trial the data used was
      from the sub-period 33-90 DIM provided by seven animals fed ad libitum with diet
      B (6.63 MJ/kg DM; 179.50 g/kg of crude protein) and by seven animals fed ad
      libitum with diet C (5.99 MJ/kg DM; 155.40 g/kg of crude protein), each of the
      diets had the same forage/concentrate ratio (53/47). A significant difference was
      found in milk production between group B and C (13.08 vs. 11.56 kg/d, p<0.05), an
      intermediate production (12.10 kg/d) was noted in group A. A significant
      difference was found between fat (76.58 vs. 69.24 g/kg, p<0.05), protein (46.14
      vs. 43.16 g/kg, p<0.05) and casein (39.94 vs. 34.98 g/kg, p<0.05) of the milk of
      group B with respect to group A. The milk of group C gave fat values (71.80
      g/kg), protein (45.52 g/kg) and casein (39.06 g/kg) statistically equal to those
      of group B. The milk of groups B and C, in respect to the milk of group A, gave
      values of K20 (1.77, 1.82 vs. 3.68 min, p<0.05), statistically lower and values
      of A30 (48.28, 47.27 vs. 40.64 mm, p<0.05) statistically higher. Two simple
      linear regressions were calculated where the independent variable (x) was the
      daily standardized milk production, the dependent variable (y) or the daily
      intake of net energy or crude protein. Equation 1) NE (MJ/d) = 74.4049+2.8308*kg
      of normalized milk; equation 2) CP (kg/d) = 1.4507+0.1085*kg of normalized milk,
      both the equations were significant (p<0.05) with determination coefficients of
      0.58 and 0.50 respectively. For a production of normalized milk that varies from
      9 to 13 kg, the respective energy-protein concentrations fluctuate from 6.09 to
      6.78 MJ/kg DM and from 148.00 to 174.46 g/kg DM. 

PMID- 25049570
TI  - Influence of Rain Tree Pod Meal Supplementation on Rice Straw Based Diets Using
      In vitro Gas Fermentation Technique.
AB  - The objective of this study was to determine the roughage to concentrate (R:C)
      ratio with rain tree pod meal (RPM) supplementation on in vitro fermentation
      using gas production technique. The experiment design was a 6*4 factorial
      arrangement in a CRD. Factor A was 6 levels of R:C ratio (100:0, 80:20, 60:40,
      40:60, 20:80 and 0:100) and factor B was 4 levels of RPM (0, 4, 8 and 12 mg). It
      was found that gas kinetic, extent rate (c) was linearly increased (p<0.01) with
      an increasing level of concentrate while cumulative gas production (96 h) was
      higher in R:C of 40:60. In addition, interaction of R:C ratio and RPM level
      affected NH3-N and IVDMD and were highest in R:C of 0:100 with 0, 4 mg of RPM and
      40:60 with 8 mg of RPM, respectively. Moreover, interaction of R:C ratio and RPM
      level significantly increased total volatile fatty acids and propionate
      concentration whereas lower acetate, acetate to propionate ratios and CH4
      production in R:C of 20:80 with 8 mg of RPM. Moreover, the two factors, R:C ratio
      and RPM level influenced the protozoal population and the percentage of
      methanogens in the total bacteria population. In addition, the use of real-time
      PCR found that a high level of concentrate in the diet remarkably decreased three
      cellulolytic bacteria numbers (F. succinogenes, R. flavefaciens and R. albus).
      Based on this study, it is suggested that the ratio of R:C at 40:60 and RPM level
      at 12 mg could improve ruminal fluid fermentation in terms of reducing
      fermentation losses, thus improving VFA profiles and ruminal ecology. 

PMID- 25049572
TI  - The Main Suppressing Factors of Dry Forage Intake in Large-type Goats.
AB  - In large-type goats that were fed on dry forage twice daily, dry forage intake
      was markedly suppressed after 40 min of feeding had elapsed. The objective of
      this study was to determine whether or not marked decreases in dry forage intake
      after 40 min of feeding are mainly caused by the two factors, that is, ruminal
      distension and increased plasma osmolality induced thirst produced by dry forage
      feeding. Six large-type male esophageal- and ruminal-fistulated goats (crossbred
      Japanese Saanen/Nubian, aged 2 to 6 years, weighing 85.1+/-4.89 kg) were used in
      two experiments. The animals were fed ad libitum a diet of roughly crushed
      alfalfa hay cubes for 2 h from 10:00 to 12:00 am during two experiments. Water
      was withheld during feeding in both experiments but was available for a period of
      30 min after completion of the 2 h feeding period. In experiment 1, saliva lost
      via the esophageal fistula was replenished by an intraruminal infusion of
      artificial parotid saliva (RIAPS) in sham feeding conditions (SFC) control, and
      the treatment was maintained under normal feeding conditions (NFC). In experiment
      2, a RIAPS and non-insertion of a balloon (RIAPS-NB) control was conducted in the
      same manner as the SFC control of experiment 1. The intraruminal infusion of
      hypertonic solution and insertion of a balloon (RIHS-IB) treatment was carried
      out simultaneously to reproduce the effects of changing salt content and ruminal
      distension due to feed entering the rumen. The results of experiment 1 showed
      that due to the effects of multiple dry forage suppressing factors when feed
      boluses entered the rumen, eating rates in the NFC treatment decreased (p<0.05)
      after 40 min of feeding and cumulative dry forage intake for the 2 h feeding
      period reduced to 43.8% of the SFC control (p<0.01). The results of experiment 2
      indicated that due to the two suppressing factors of ruminal distension and
      increased plasma osmolality induced thirst, eating rates in the RIHS-IB treatment
      were, as observed under NFC, reduced (p<0.05) and cumulative dry forage intake
      for the 2 h feeding period decreased to 34.0% of the RIAPS-NB control (p<0.01).
      The combined effects of ruminal distension and increased plasma osmolality
      accounted for 77.5% of the suppression of dry forage intake 40 min after the
      start of dry forage feeding. The results indicate that ruminal distension and
      increased plasma osmolality induced thirst are the main factors in the
      suppression of dry forage intake in large-type goats. 

PMID- 25049573
TI  - Evaluation of Milk Trace Elements, Lactate Dehydrogenase, Alkaline Phosphatase
      and Aspartate Aminotransferase Activity of Subclinical Mastitis as and Indicator
      of Subclinical Mastitis in Riverine Buffalo (Bubalus bubalis).
AB  - Mastitis is a highly morbid disease that requires detection at the subclinical
      stage. Tropical countries like India mainly depend on milch buffaloes for milk.
      The present study was conducted to investigate whether the trace minerals viz.
      copper (Cu), iron (Fe), zinc (Zn), cobalt (Co) and manganese (Mn) and enzyme
      activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate
      aminotransferase (AST) in riverine buffalo milk can be used as an indicator of
      subclinical mastitis (SCM) with the aim of developing suitable diagnostic kit for
      SCM. Trace elements and enzyme activity in milk were estimated with Atomic
      absorption Spectrophotometer, GBC 932 plus and biochemical methods, respectively.
      Somatic cell count (SCC) was done microscopically. The cultural examination
      revealed Gram positive bacteria as the most prevalent etiological agent. A
      statistically significant (p<0.01) increase in SCC, Fe, Zn, Co and LDH occurred
      in SCM milk containing gram positive bacterial agents only. ALP was found to be
      elevated in milk infected by both gram positive and negative bacteria. The
      percent sensitivity, specificity and accuracy, predictive values and likelihood
      ratios were calculated taking bacterial culture examination and SCC>=2*10(5)
      cells/ml of milk as the benchmark. Only ALP and Zn, the former being superior,
      were found to be suitable for diagnosis of SCM irrespective of etiological
      agents. LDH, Co and Fe can be introduced in the screening programs where Gram
      positive bacteria are omnipresent. It is recommended that both ALP and Zn be
      measured together in milk to diagnose buffalo SCM, irrespective of etiology. 

PMID- 25049574
TI  - Hemato-biochemical and Cortisol Profile of Holstein Growing-calves Supplemented
      with Vitamin C during Summer Season.
AB  - Effect of vitamin C (VC) on biochemical, hematological and cortisol profile of
      growing Holstein calves during summer was investigated. Eighteen calves between
      14 and 16 weeks of age were divided equally into two groups. One group received a
      diet supplemented with VC (20 g/d) for 60 days, while other non-supplemented diet
      fed group served as a control (CON). The temperature humidity index (THI) was
      recorded and computed during the experiment. From days 0 to 60, the THI exceeded
      70. Blood samples were collected from the jugular vein of each calf at days 0,
      15, 30, 45 and 60. Serum albumin and total protein decreased (p<0.05) in CON and
      VC calves with age. Serum glutamic-oxaloacetic transaminase concentrations were
      not affected by treatments. Serum creatinine, albumin and glutamic-pyruvic
      transaminase concentrations were higher in calves in the VC group than the CON
      group. While red blood cells, hemoglobin and hematocrit were lower (p<0.05) in VC
      calves, mean corpuscular volume, mean corpuscular hemoglobin, red blood cell
      distribution width and mean platelet volume were higher (p<0.05) in these VC
      supplemented calves. Leukocyte parameters including white blood cells and full
      term for lymphocytes were not affected by the treatments. Also, serum cortisol
      was not affected by treatments. At day 15, 30 and 45, the total VC in plasma was
      higher (p<0.05) in calves fed with VC. In conclusion, serum cortisols were not
      affected by plasma VC concentration, while some blood parameters were positively
      influenced in calves fed with VC. 

PMID- 25049575
TI  - Effects of Dietary Protein and Lipid Levels on Growth and Body Composition of
      Juvenile Far Eastern Catfish Silurus asotus.
AB  - A 3*2 factorial experiment was conducted to determine the effects of dietary
      protein and lipid levels on the growth and body composition of juvenile far
      eastern catfish. Six diets were formulated to contain three levels of protein
      (20%, 30% and 40%) and two levels of lipid (9% and 17%). Triplicate groups of
      fish (initial body weight of 7.6 g) were hand-fed to apparent satiation for 66
      days. Final mean weight was improved with increasing dietary protein and lipid
      levels, and the highest final mean weight was observed in fish fed the 40/17 (%
      protein/% lipid) diet. No significant difference was observed in final mean
      weight for fish fed between 30/17 diet and 40/9 diet. Feed efficiency of fish fed
      the diets containing over 30% protein levels with 9% and 17% lipid levels were
      significantly higher than those of fish fed the 20% protein levels. Feed
      efficiency of fish fed the 30/17 diet was not significantly different from that
      of fish fed the 40/9 diet or 40/17 diet. Feed efficiency and protein efficiency
      ratio of fish fed the 20% protein diets with 17% lipid level were significantly
      higher than those of fish fed 9% lipid diet. Daily feed intake of fish tended to
      decrease with increasing dietary protein and lipid levels. Moisture content of
      whole body in fish fed the 9% lipid diets was significantly higher than that of
      fish fed the 17% lipid diets at the same protein level, but the opposite trends
      were found for crude lipid content. Significant effects of dietary lipid were
      observed for most fatty acids, according to their relative values in the diets.
      The results of this study suggest that the protein requirement for maximum growth
      of juvenile far eastern catfish may be higher than 40%, and an increase of
      dietary lipid level from 9% to 17% can improve growth and feed utilization. 

PMID- 25049576
TI  - Predicting the Digestible Energy of Rapeseed Meal from Its Chemical Composition
      in Growing-finishing Pigs.
AB  - Two experiments were conducted to establish a digestible energy (DE) content
      prediction model of rapeseed meal for growing-finishing pig based on rapeseed
      meal's chemical composition. In experiment 1, observed linear relationships
      between the determined DE content of 22 rapeseed meal calibration samples and
      proximate nutrients, gross energy (GE) and neutral detergent fiber (NDF) were
      used to develop the DE prediction model. In experiment 2, 4 samples of rapeseed
      meal selected at random from the primary rapeseed growing regions of China were
      used for testing the accuracy of DE prediction models. The results indicated that
      the DE was negatively correlated with NDF (r = -0.86) and acid detergent fiber
      (ADF) (r = -0.73) contents, and moderately correlated with gross energy (GE; r =
      0.56) content in rapeseed meal calibration samples. In contrast, no significant
      correlations were found for crude protein, ether extract, crude fiber and ash
      contents. According to the regression analysis, NDF or both NDF and GE were found
      to be useful for the DE prediction models. Two prediction models: DE = 16.775
      0.147*NDF (R(2) = 0.73) and DE = 11.848-0.131*NDF+0.231*GE (R(2) = 0.76) were
      obtained. The maximum absolute difference between the in vivo DE determinations
      and the predicted DE values was 0.62 MJ/kg and the relative difference was 5.21%.
      Therefore, it was concluded that, for growing-finishing pigs, these two
      prediction models could be used to predict the DE content of rapeseed meal with
      acceptable accuracy. 

PMID- 25049577
TI  - Effect of dietary antimicrobials on immune status in broiler chickens.
AB  - This study evaluated the effects of dietary anticoccidial drugs plus antibiotic
      growth promoters (AGPs) on parameters of immunity in commercial broiler chickens.
      Day-old chicks were raised on used litter from a farm with endemic gangrenous
      dermatitis to simulate natural pathogen exposure and provided with diets
      containing decoquinate (DECX) or monensin (COBN) as anticoccidials plus
      bacitracin methylene disalicylate and roxarsone as AGPs. As a negative control,
      the chickens were fed with a non-supplemented diet. Immune parameters examined
      were concanavalin A (ConA)-stimulated spleen cell proliferation, intestine
      intraepithelial lymphocyte (IEL) and spleen cell subpopulations, and
      cytokine/chemokine mRNA levels in IELs and spleen cells. ConA-induced
      proliferation was decreased at 14 d post-hatch in DECX-treated chickens, and
      increased at 25 and 43 d in COBN-treated animals, compared with untreated
      controls. In DECX-treated birds, increased percentages of MHC2(+) and CD4(+) IELS
      were detected at 14 d, but decreased percentages of these cells were seen at 43
      d, compared with untreated controls, while increased TCR2(+) IELs were evident at
      the latter time. Dietary COBN was associated with decreased fractions of MHC2(+)
      and CD4(+) IELs and reduced percentages of MHC2(+), BU1(+), and TCR1(+) spleen
      cells compared with controls. The levels of transcripts for interleukin-4 (IL-4),
      IL-6, IL-17F, IL-13, CXCLi2, interferon-gamma (IFN-gamma), and transforming
      growth factorbeta4 were elevated in IELs, and those for IL-13, IL-17D, CXCLi2,
      and IFN-gamma were increased in spleen cells, of DECX- and/or COBN-treated
      chickens compared with untreated controls. By contrast, IL-2 and IL-12 mRNAs in
      IELs, and IL-4, IL-12, and IL-17F transcripts in spleen cells, were decreased in
      DECX- and/or COBN-treated chickens compared with controls. These results suggest
      that DECX or COBN, in combination with bacitracin and roxarsone, modulate the
      development of the chicken post-hatch immune system. 

PMID- 25049578
TI  - Effects of Replacement of Soybean Meal by Fermented Cottonseed Meal on Growth
      Performance, Serum Biochemical Parameters and Immune Function of Yellow-feathered
      Broilers.
AB  - The study was conducted to examine the effects of partially replacing soybean
      meal (SBM) by solid-state fermented cottonseed meal (FCSM) on growth performance,
      serum biochemical parameters and immune function of broilers. After inoculated
      with Bacillus subtilis BJ-1 for 48 h, the content of free gossypol in cottonseed
      meal was decreased from 0.82 to 0.21 g/kg. A total of 600, day-old male yellow
      feathered broilers were randomly divided into four groups with three replicates
      of 50 chicks each. A corn-SBM based control diet was formulated and the
      experimental diets included 4, 8 or 12% FCSM, replacing SBM. Throughout the
      experiment, broilers fed 8% FCSM had higher (p<0.05) body weight gain than those
      fed 0, 4 and 12% FCSM. The feed intake in 8% FCSM group was superior (p<0.05) to
      other treatments from d 21 to 42. On d 21, the concentration of serum
      immunoglobin M in the 4% and 8% FCSM groups, as well as the content of
      complements (C3, C4) in 8% FCSM group were greater (p<0.05) than those in the SBM
      group. Besides, birds fed 8% FCSM had increased (p<0.05) serum immunoglobin M,
      immunoglobulin G and complement C4 levels on d 42 compared with bird fed control
      diet. No differences (p>0.05) were found between treatments regarding the serum
      biochemical parameters and the relative weights of immune organs. In conclusion,
      FCSM can be used in broiler diets at up to 12% of the total diet and an
      appropriate replacement of SBM with FCSM may improve growth performance and
      immunity in broilers. 

PMID- 25049579
TI  - Nutritional evaluation of distillery sludge and its effect as a substitute of
      canola meal on performance of broiler chickens.
AB  - The study was conducted to investigate the chemical composition of distillery
      yeast sludge and its inclusion in broiler diets to replace canola meal. Raw
      distillery yeast sludge was washed with water using water and sludge in the ratio
      6:1, respectively. Proximate analysis of raw distillery yeast sludge and washed
      distillery sludge was carried out for crude protein (CP), true protein (TP),
      ether extract (EE), ash, acid insoluble ash and nitrogen free extract (NFE)
      determination. Mineral contents and amino acid profile of raw distillery yeast
      sludge and washed distillery sludge were also determined. After chemical
      evaluation, four iso-caloric and iso-nitrogenous broiler starter and finisher
      diets were prepared in mash form using 0 (control), 4, 8 and 12% levels of washed
      distillery sludge replacing canola meal. One hundred and twenty day-old broiler
      chicks were randomly distributed into 12 experimental units in such a way that
      each diet was offered to three experimental units, each comprising of 10 chicks.
      It was observed that washing affected the nutrients either by decreasing or
      increasing their concentration. It decreased the total mineral contents whereas
      CP, TP, EE and NFE contents increased. Washing also increased amino acid profile.
      Average feed intake and weight gain were higher in birds fed diet containing 8%
      washed distillery sludge and lower in birds fed diet containing 0% washed
      distillery sludge. Feed cost per kg live weight gain decreased significantly as
      the level of washed distillery sludge was increased in the diet. Average heart,
      liver and pancreas weights decreased with increased level of washed distillery
      sludge in the diet. The study revealed that after washing, distillery yeast
      sludge can be used successfully in broiler diets up to the level of 8% without
      any adverse effect on broiler's performance. 

PMID- 25049580
TI  - Daily feed intake, energy intake, growth rate and measures of dietary energy
      efficiency of pigs from four sire lines fed diets with high or low metabolizable
      and net energy concentrations.
AB  - A TRIAL WAS CONDUCTED TO: i) evaluate the BW growth, energy intakes and energetic
      efficiency of pigs fed high and low density diets from 27 to 141 kg BW, ii)
      evaluate sire line and sex differences when fed both diets, and iii) to compare
      ME to NE as predictor of pig performance. The experiment had a replicated
      factorial arrangement of treatments including four sire lines, two sexes (2,192
      barrows and 2,280 gilts), two dietary energy densities and a light or heavy
      target BW, 118 and 131.5 kg in replicates 1 to 6 and 127 and 140.6 kg in
      replicates 7 to 10. Pigs were allocated to a series of low energy (LE, 3.27 Mcal
      ME/kg) corn-soybean meal based diets with 16% wheat midds or high energy diets
      (HE, 3.53 to 3.55 Mcal ME/kg) with 4.5 to 4.95% choice white grease. All diets
      contained 6% DDGS. The HE and LE diets of each of the four phases were formulated
      to have equal lysine:Mcal ME ratios. Pigs were weighed and pen feed intake (11 or
      12 pigs/pen) recorded at 28-d intervals. The barrow and gilt daily feed (DFI), ME
      (MEI) and NE (NEI) intake data were fitted to a Bridges function of BW. The BW
      data of each sex were fitted to a generalized Michaelis-Menten function of days
      of age. ME and NE required for maintenance (Mcal/d) were predicted using
      functions of BW (0.255 and 0.179 BW^0.60 respectively). Pigs fed LE diets had
      decreased ADG (915 vs. 945 g/d, p<0.001) than pigs fed HE diets. Overall, DFI was
      greater (p<0.001) for pigs fed the LE diets (2.62 vs. 2.45 kg/d). However, no
      diet differences were observed for MEI (8.76 vs. 8.78 Mcal/d, p = 0.49) or NEI
      (6.39 vs. 6.44 Mcal/d, p = 0.13), thereby indicating that the pigs compensated
      for the decreased energy content of the diet. Overall ADG:DFI (0.362 vs. 0.377)
      and ADG:Mcal MEI (0.109 vs. 0.113) was less (p<0.001) for pigs fed LE compared to
      HE diets. Pigs fed HE diets had 3.6% greater ADG:Mcal MEI above maintenance and
      only 1.3% greater ADG:Mcal NEI (0.152 versus 0.150), therefore NEI is a more
      accurate predictor of growth and G:F than MEI. Pigs fed HE diets had 3.4% greater
      ADG:Mcal MEI and 0.11% greater ADG:NEI above maintenance than pigs fed LE diets,
      again demonstrating that NEI is a better predictor of pig performance than MEI.
      Pigs fed LE diets had similar daily NEI and MEI but grew slower and less
      efficiently on both ME and NE basis than pigs fed HE diets. The data suggest that
      the midds NE value (2.132 Mcal/kg) was too high for this source or that
      maintenance was increased for pigs fed LE diets.

PMID- 25049582
TI  - The quality of modified atmosphere packaged meat from lambs slaughtered at 50 and
      100 days of age.
AB  - The aim of this study was to determine the quality of modified atmosphere (MA)
      packaged meat from Pomeranian rams slaughtered at 50 and 100 days of age.
      Determined: chemical composition, physicochemical and sensory properties of meat,
      and the fatty acid profile of intramuscular fat. Meat from 100-d-old lambs was
      characterized by a significantly higher content of dry matter, total protein and
      crude fat, a darker color and higher physiological maturity (p<=0.01). Meat from
      younger lambs was marked by a better water-holding capacity (p<=0.05), a lower
      energy value and higher concentrations of monounsaturated fatty acids (MUFA) and
      polyunsaturated fatty acids (PUFA). An increase in the content of dry matter,
      total protein and ash, and energy value was noted in MA-stored meat. Meat pH
      decreased over MA storage and the sensory properties deteriorated. The studied
      meat remained safe from microbial contamination during storage. 

PMID- 25049581
TI  - Cloning and Molecular Characterization of Porcine beta-casein Gene (CNS2).
AB  - The production of therapeutic proteins from transgenic animals is one of the most
      important successes of animal biotechnology. Milk is presently the most mature
      system for production of therapeutic proteins from a transgenic animal.
      Specifically, beta-casein is a major component of cow, goat and sheep milk, and
      its promoter has been used to regulate the expression of transgenic genes in the
      mammary gland of transgenic animals. Here, we cloned the porcine beta-casein gene
      and analyzed the transcriptional activity of the promoter and intron 1 region of
      the porcine beta-casein gene. Sequence inspection of the 5'-flanking region
      revealed potential DNA elements including SRY, CdxA, AML-a, GATA-3, GATA-1 and
      C/EBP beta. In addition, the first intron of the porcine beta-casein gene
      contained the transcriptional enhancers Oct-1, SRY, YY1, C/EBP beta, and AP-1, as
      well as the retroviral TATA box. We estimated the transcriptional activity for
      the 5'-proximal region with or without intron 1 of the porcine beta-casein gene
      in HC11 cells stimulated with lactogenic hormones. High transcriptional activity
      was obtained for the 5'-proximal region with intron 1 of the porcine beta-casein
      gene. The beta-casein gene containing the mutant TATA box (CATAAAA) was also
      cloned from another individual pig. Promoter activity of the luciferase vector
      containing the mutant TATA box was weaker than the same vector containing the
      normal TATA box. Taken together, these findings suggest that the transcription of
      porcine beta-casein gene is regulated by lactogenic hormone via intron 1 and
      promoter containing a mutant TATA box (CATAAAA) has poor porcine beta-casein gene
      activity. 

PMID- 25049583
TI  - Flavor characteristics of hanwoo beef in comparison with other korean foods.
AB  - The present study identified volatile flavor components of Hanwoo longissimus
      muscle and other Korean foods (Doenjang, Chungukjang, sesame oil) and their
      traits were compared in relation with flavor precursors that include fatty acids
      and protein degradation products. Hanwoo longissimus muscle was purchased from a
      commercial abattoir while the other foods were sampled from three separate
      households. The results showed totals of 68 (9.94 MUg/g), 60 (15.75 MUg/g), 49
      (107.61 MUg/ml) and 50 (7.20 MUg/g) volatile components for Doenjang,
      Chungukjang, sesame oil and Hanwoo beef longissimus, respectively (p<0.05).
      Aldehydes were the most predominant components in beef, but alcohols, acids and
      esters, and pyrazines are probably the major contributors to the flavor
      characteristics of other foods. SDS-PAGE revealed that beef longissimus muscle
      and Doenjang showed higher protein degradation than other foods which could be
      likely related to chiller ageing and ripening process. The total polyunsaturated
      fatty acids were approximately 50, 60, 41 and 5% for Doenjang, Chungukjang,
      sesame oil and beef longissimus muscle, respectively. Based on the mechanism(s)
      of generation of the volatile compounds and the chemical composition of each food
      sample, differences and traits of volatile flavor components among the four food
      types are likely due to fatty acid profiles, proteolytic activity and processing
      conditions. Aroma intense compounds like pyrazines and sulfur-containing
      compounds were limited in cooked beef in the current experimental condition
      (i.e., relatively low heating temperature). This suggests that higher heating
      temperature as in the case of roasting is needed for the generation of high aroma
      notes in meat. Furthermore, proteolytic activity and stability of fatty acids
      during ageing have a great influence on the generation of flavor components in
      cooked beef. 

PMID- 25049584
TI  - Prevalence, risk factors and consequent effect of dystocia in holstein dairy cows
      in iran.
AB  - The objective of this research was to determine the prevalence, risk factors and
      consequent effect of dystocia on lactation performance in Holstein dairy cows in
      Iran. The data set consisted of 55,577 calving records on 30,879 Holstein cows in
      30 dairy herds for the period March 2000 to April 2009. Factors affecting
      dystocia were analyzed using multivariable logistic regression models through the
      maximum likelihood method in the GENMOD procedure. The effect of dystocia on
      lactation performance and factors affecting calf birth weight were analyzed using
      mixed linear model in the MIXED procedure. The average incidence of dystocia was
      10.8% and the mean (SD) calf birth weight was 42.13 (5.42) kg. Primiparous cows
      had calves with lower body weight and were more likely to require assistance at
      parturition (p<0.05). Female calves had lower body weight, and had a lower odds
      ratio for dystocia than male calves (p<0.05). Twins had lower birth weight, and
      had a higher odds ratio for dystocia than singletons (p<0.05). Cows which gave
      birth to a calf with higher weight at birth experienced more calving difficulty
      (OR (95% CI) = 1.1(1.08-1.11). Total 305-d milk, fat and protein yield was 135
      (23), 3.16 (0.80) and 6.52 (1.01) kg less, in cows that experienced dystocia at
      calving compared with those that did not (p<0.05). 

PMID- 25049585
TI  - Enhancing mulberry leaf meal with urea by pelleting to improve rumen fermentation
      in cattle.
AB  - Four, ruminally fistulated crossbred (Brahman*native) beef cattle with initial
      body weight of 420+/-15 kg were randomly assigned according to a 4*4 Latin square
      design. The dietary treatments were mulberry leaf pellet (MUP) supplementation at
      0, 200, 400 and 600 g/hd/d with rice straw fed to allow ad libitum intake. All
      steers were kept in individual pens and supplemented with concentrate at 5 g/kg
      of body weight daily. The experiment was 4 periods, and each lasted 21 d. During
      the first 14 d, all steers were fed their respective diets ad libitum and during
      the last 7 d, they were moved to metabolism crates for total urine and fecal
      collection. It was found that increasing MUP levels resulted in linearly
      increasing rice straw and total intakes (p<0.05). Ruminal temperature and pH were
      not significantly affected by MUP supplementation while NH3-N concentration was
      increased (p<0.05) and maintained at a high level (18.5 mg/dl) with
      supplementation of MUP at 600 g/hd/d. Similarly, viable total bacteria in the
      rumen and cellulolytic bacteria were enriched by MUP supplementation at 600
      g/hd/d. However, the rumen microbial diversity determined with a PCR-DGGE
      technique showed similar methanogenic diversity between treatments and sampling
      times and were similar at a 69% genetic relationship as determined by a UPGMA
      method. Based on this study, it could be concluded that supplementation of MUP at
      600 g/hd/d improved DM intake, ruminal NH3-N, and cellulolytic bacteria thus
      iimproving rumen ecology in beef cattle fed with rice straw. 

PMID- 25049586
TI  - Modeling and forecasting livestock feed resources in India using climate
      variables.
AB  - The availability and efficient use of the feed resources in India are the primary
      drivers to maximize productivity of Indian livestock. Feed security is vital to
      the livestock management, extent of use, conservation and productivity
      enhancement. Assessment and forecasting of livestock feed resources are most
      important for effective planning and policy making. In the present study, 40
      years of data on crop production, land use pattern, rainfall, its deviation from
      normal, area under crop and yield of crop were collected and modeled to forecast
      the likely production of feed resources for the next 20 years. The higher order
      auto-regressive (AR) models were used to develop efficient forecasting models.
      Use of climatic variables (actual rainfall and its deviation from normal) in
      combination with non-climatic factors like area under each crop, yield of crop,
      lag period etc., increased the efficiency of forecasting models. From the best
      fitting models, the current total dry matter (DM) availability in India was
      estimated to be 510.6 million tonnes (mt) comprising of 47.2 mt from
      concentrates, 319.6 mt from crop residues and 143.8 mt from greens. The
      availability of DM from dry fodder, green fodder and concentrates is forecasted
      at 409.4, 135.6 and 61.2 mt, respectively, for 2030. 

PMID- 25049587
TI  - Potential Water Retention Capacity as a Factor in Silage Effluent Control:
      Experiments with High Moisture By-product Feedstuffs.
AB  - The role of moisture absorptive capacity of pre-silage material and its
      relationship with silage effluent in high moisture by-product feedstuffs (HMBF)
      is assessed. The term water retention capacity which is sometimes used in
      explaining the rate of effluent control in ensilage may be inadequate, since it
      accounts exclusively for the capacity of an absorbent incorporated into a pre
      silage material prior to ensiling, without consideration to how much the pre
      silage material can release. A new terminology, 'potential water retention
      capacity' (PWRC), which attempts to address this shortcoming, is proposed. Data
      were pooled from a series of experiments conducted separately over a period of
      five years using laboratory silos with four categories of agro by-products (n =
      27) with differing moisture contents (highest 96.9%, lowest 78.1% in fresh
      matter, respectively), and their silages (n = 81). These were from a vegetable
      source (Daikon, Raphanus sativus), a root tuber source (potato pulp), a fruit
      source (apple pomace) and a cereal source (brewer's grain), respectively. The pre
      silage materials were adjusted with dry in-silo absorbents consisting wheat
      straw, wheat or rice bran, beet pulp and bean stalks. The pooled mean for the
      moisture contents of all pre-silage materials was 78.3% (+/-10.3). Silage
      effluent decreased (p<0.01), with increase in PWRC of pre-silage material. The
      theoretical moisture content and PWRC of pre-silage material necessary to stem
      effluent flow completely in HMBF silage was 69.1% and 82.9 g/100 g in fresh
      matter, respectively. The high correlation (r = 0.76) between PWRC of ensiled
      material and silage effluent indicated that the latter is an important factor in
      silage-effluent relationship. 

PMID- 25049588
TI  - Improvement of Fermentation and Nutritive Quality of Straw-grass Silage by
      Inclusion of Wet Hulless-barley Distillers' Grains in Tibet.
AB  - In order to develop methods that would enlarge the feed resources in Tibet,
      mixtures of hulless-barley straw and tall fescue were ensiled with four levels
      (0, 10%, 20%, and 30% of fresh weight) of wet hulless-barley distillers' grains
      (WHDG). The silos were opened after 7, 14 or 30 d of ensiling, and the
      fermentation characteristics and nutritive quality of the silages were analyzed.
      WHDG addition significantly improved fermentation quality, as indicated by the
      faster decline of pH, rapid accumulation of lactic acid (LA) (p<0.05), and lower
      butyric acid content and ammonia-N/total N (p<0.05) as compared with the control.
      These results indicated that WHDG additions not only effectively inhibited the
      activity of aerobic bacteria, but also resulted in faster and greatly enhanced LA
      production and pH value decline, which restricted activity of undesirable
      bacteria, resulting in more residual water soluble carbohydrates (WSC) in the
      silages. The protein content of WHDG-containing silages were significantly higher
      (p<0.05) higher than that of the control. In conclusion, the addition of WHDG
      increased the fermentation and nutritive quality of straw-grass silage, and this
      effect was more marked when the inclusion rate of WHDG was greater than 20%. 

PMID- 25049589
TI  - Effect of Dietary Cation-Anion Difference during Prepartum and Postpartum Periods
      on Performance, Blood and Urine Minerals Status of Holstein Dairy Cow.
AB  - Twenty four periparturient cows were used to determine the effects of DCAD on
      acid-base balance, plasma and urine mineral concentrations, health status, and
      subsequent lactation performance. Each group of 12 cows received either a diet
      containing -100 DCAD or +100 DCAD for 21 d prepartum. Both anionic and cationic
      groups were divided into two groups, one received a +200 DCAD and the other +400
      DCAD diet for 60 d postpartum. Prepartum reduction of DCAD decreased DMI, urinary
      and blood pH, urinary concentrations of Na or K and increased plasma and urinary
      Ca, Mg, Cl and S. Also cows fed -100 DCAD diet consumed the most dry matter in
      the first 60 d after calving. Postpartum +400 DCAD increased milk fat and total
      solid percentages, urinary and blood pH and urinary Na and K concentrations, but
      urinary Ca, P, Cl and S contents decreased. Greater DMI, FCM yields were observed
      in cows fed a diet of +400 DCAD than +200 DCAD. No case of milk fever occurred
      for any diets but feeding with a negative DCAD diet reduced placenta expulsion
      time. In conclusion, feeding negative DCAD in late gestation period and high DCAD
      in early lactation improves performance and productivity of dairy cows. 

PMID- 25049590
TI  - Indirect Estimation of CH4 from Livestock Feeds through TOCs Evaluation.
AB  - Thirty-five available feeds were fermented in vitro in order to investigate their
      soluble total organic carbon (TOCs) and methane (CH4) production rate. A
      fermentation reactor was designed to capture the CH4 gas emitted and to collect
      liquor from the reactor during in vitro fermentation. The results showed that CH4
      production rate greatly varied among feeds with different ingredients. The lowest
      CH4-producing feeds were corn gluten feed, brewer's grain, and orchard grass
      among the energy, protein, and forage feed groups, respectively. Significant
      differences (p<0.05) were found in digestibility, soluble total organic carbon
      (TOCs), and CH4 emissions among feeds, during 48 h of in vitro fermentation.
      Digestibility and TOCs was not found to be related due to different fermentation
      pattern of each but TOCs production was directly proportional to CH4 production
      (y = 0.0076x, r(2) = 0.83). From this in vitro study, TOCs production could be
      used as an indirect index for estimation of CH4 emission from feed ingredients. 

PMID- 25049591
TI  - A Physiological Stimulating Factor of Water Intake during and after Dry Forage
      Feeding in Large-type Goats.
AB  - When ruminants consume dry forage, they also drink large volumes of water. The
      objective of this study was to clarify which factor produced when feed boluses
      enter the rumen is mainly responsible for the marked increase in water intake in
      the second hour of the 2 h feeding period in large-type goats fed on dry forage
      for 2 h twice daily. Six large-type male esophageal- and ruminal-fistulated goats
      (crossbred Japanese Saanen/Nubian, aged 2 to 6 years, weighing 85.1+/-4.89 kg)
      were used in two experiments. In experiment 1, the water deprivation (WD) control
      and the water availability (WA) treatment were conducted to compare changes in
      water intake during and after dry forage feeding. In experiment 2, a normal
      feeding conditions (NFC) control and a feed bolus removal (FBR) treatment were
      carried out to investigate whether decrease in circulating plasma volume or
      increase in plasma osmolality is mainly responsible for the marked increase in
      water intake in the second hour of the 2 h feeding period. The results of
      experiment 1 showed that in the WA treatment, small amounts of water were
      consumed during the first hour of feeding while the majority of water intake was
      observed during the second hour of the 2 h feeding period. Therefore, the amounts
      of water consumed in the second hour of the 2 h feeding period accounted for
      82.8% of the total water intake. The results of experiment 2 indicated that in
      comparison with the NFC control, decrease in plasma volume in the FBR treatment,
      which was indicated by increase in hematocrit and plasma total protein
      concentrations, was higher (p<0.05) in the second hour of the 2 h feeding period.
      However, plasma osmolality in the FBR treatment was lower (p<0.05) than compared
      to the NFC control from 30 min after the start of feeding. Therefore, thirst
      level in the FBR treatment was 82.7% less (p<0.01) compared with that in the NFC
      control upon conclusion of the 30 min drinking period. The results of the study
      indicate that the increased plasma osmolality in the second hour of the 2 h
      feeding period is the main physiological stimulating factor of water intake
      during and after dry forage feeding in large-type goats. 

PMID- 25049592
TI  - Effect of xylanase on performance and apparent metabolisable energy in starter
      broilers fed diets containing one maize variety harvested in different regions of
      china.
AB  - The objective of this study was to investigate the variability in broiler
      performance, apparent metabolisable energy (AME) and ileal digestible energy
      (IDE) between five different maize samples fed with and without xylanase at
      16,000 U/kg. Various in vitro characterisations were conducted to determine if
      any could predict performance or AME. Samples of the maize were harvested in five
      diverse regions and fed individually in a mash diet as follows (g/kg): test maize
      608.3; soya bean meal (SBM) 324.1; poultry fat 25.2; salt 4.6; met 2.6; lys 1.6;
      thr 0.5; limestone 9.7, dical 18.4; vit/min 5.0; CP 210 and ME (kcal/kg) 3,085.
      The diets were fed to 720 broilers with 6 replicates, each containing 12 birds
      per treatment, from 0 to 18 d of age. Maize samples were analysed for starch,
      protein, crude fibre, fat, protein solubility index (PSI) and vitreousness using
      near infra red reflectance spectroscopy (NIR). They were also assayed using an in
      vitro starch digestibility method. The results showed that there was no effect of
      harvest region on the feed intake (FI), body weight gain (BWG) or feed conversion
      ratio (FCR) of the broilers over the 18 d period (p = 0.959, 0.926, 0.819
      respectively). There was an improvement in all parameters with the addition of
      xylanase (FI p = 0.011; BWG and FCR p<0.001). There was a significant positive
      effect of xylanase on IDE, AME, IDE Intake (IDEI) and AME intake (AMEI) (p<0.0001
      in all cases). Although there was no significant effect of maize source, there
      was a strong trend towards variability in IDE (p = 0.066) and AME (p = 0.058).
      There were no significant correlations (p<0.05) between any proximate or
      physiochemical values and any performance or AME values. This may suggest that
      none of those selected were suitable predictors for performance or AME. The
      broilers performed well according to the breed guidelines, with slightly
      increased FI, increased BWG and similar FCR prior to the addition of xylanase.
      When FCR and BWG were analysed with FI as a covariate, xylanase addition remained
      significant suggesting that the improvement in BWG and FCR was driven by an
      increase in digestibility and nutrient availability. 

PMID- 25049593
TI  - The Long Term Effects of Fairly Low-level of Supplemental Fat on the Productive
      Performance of Commercial Layers.
AB  - Laying hens were fed commercial diets added with supplemented fat (SFAT) at 0.6,
      1.2, and 1.8% in order to study the long term dietary effects - on - their
      productive performance from 22 to 75 wk of age. Five hundred and seventy six
      Single Comb White Leghorn hens were assigned to one of the four dietary
      treatments. The experimental phase consisted of three periods of 18 wk each. The
      final body weight and gain of hens fed on diets with SFAT at 1.2% and 1.8% were
      lower (p<0.05) than those hens given no SFAT. The SFAT at the 1.2% and 1.8%
      levels improved egg production rate, egg weight and mass, as well as FCR.
      Mortality and feed consumption were not affected by dietary SFAT. Administration
      of a diet with SFAT significantly decreased the cracked-broken egg ratio
      (p<0.01). The beneficial effects of SFAT on egg production performance were
      particularly more pronounced at intermediate and later ages. Hence, SFAT by
      period interactions were significant for all traits studied except feed intake.
      Hens fed SFAT deposited significantly higher abdominal fat than those on the no
      SFAT diet. As a result, SFAT at 1.2% and 1.8% inclusion levels provided benefits
      in terms of efficient table egg production. 

PMID- 25049594
TI  - The impact of feeding diets of high or low energy concentration on carcass
      measurements and the weight of primal and subprimal lean cuts.
AB  - Pigs from four sire lines were allocated to a series of low energy (LE, 3.15 to
      3.21 Mcal ME/kg) corn-soybean meal-based diets with 16% wheat midds or high
      energy diets (HE, 3.41 to 3.45 Mcal ME/kg) with 4.5 to 4.95% choice white grease.
      All diets contained 6% DDGS. The HE and LE diets of each of the four phases were
      formulated to have equal lysine:Mcal ME ratios. Barrows (N = 2,178) and gilts (N
      = 2,274) were fed either high energy (HE) or low energy (LE) diets from 27 kg BW
      to target BWs of 118, 127, 131.5 and 140.6 kg. Carcass primal and subprimal cut
      weights were collected. The cut weights and carcass measurements were fitted to
      allometric functions (Y = A CW(B)) of carcass weight. The significance of diet,
      sex or sire line with A and B was evaluated by linearizing the equations by log
      to log transformation. The effect of diet on A and B did not interact with sex or
      sire line. Thus, the final model was (B)) where Diet = -0.5 for the LE and 0.5
      for HE diets and A and B are sire line-sex specific parameters. cut weight =
      (1+bD(Diet)) A(CW Diet had no affect on loin, Boston butt, picnic, baby back rib,
      or sparerib weights (p>0.10, bD = -0.003, -0.0029, 0.0002, 0.0047, -0.0025,
      respectively). Diet affected ham weight (bD = -0.0046, p = 0.01), belly weight
      (bD = 0.0188, p = 0.001) three-muscle ham weight (bD = -0.014, p = 0.001),
      boneless loin weight (bD = -0.010, p = 0.001), tenderloin weight (bD = -0.023, p
      = 0.001), sirloin weight (bD = -0.009, p = 0.034), and fat-free lean mass (bD = 
      0.0145, p = 0.001). Overall, feeding the LE diets had little impact on primal cut
      weight except to decrease belly weight. Feeding LE diets increased the weight of
      lean trimmed cuts by 1 to 2 percent at the same carcass weight. 

PMID- 25049595
TI  - Effects of Dietary Additives and Early Feeding on Performance, Gut Development
      and Immune Status of Broiler Chickens Challenged with Clostridium perfringens.
AB  - The effects of dietary additives and holding time on resistance and resilience of
      broiler chickens to Clostridium perfringens challenge were investigated by
      offering four dietary treatments. These were a negative control (basal), a
      positive control (Zn-bacitracin) and two dietary additives,
      mannanoligosaccharides (MOS), and acidifier. Two holding times included (a)
      immediate access to feed and water post hatch (FED) and (b) access to both feed
      and water 48 h post hatch (HELD). Chicks fed Zn-bacitracin had no intestinal
      lesions attributed to necrotic enteritis (NE), whereas chicks fed both MOS or
      acidifier showed signs of NE related lesions. All dietary treatments were
      effective in reducing the numbers of C. perfringens in the ileum post challenge.
      The FED chicks had heavier body weight and numerically lower mortality. The FED
      chicks also showed stronger immune responses to NE challenge, showing enhanced
      (p<0.05) proliferation of T-cells. Early feeding of the MOS supplemented diet
      increased (p<0.05) IL-6 production. The relative bursa weight of the FED chicks
      was heavier at d 21 (p<0.05). All the additives increased the relative spleen
      weight of the HELD chicks at d 14 (p<0.05). The FED chicks had increased villus
      height and reduced crypt depth, and hence an increased villus/crypt ratio,
      especially in the jejunum at d 14 (p<0.05). The same was true for the HELD chicks
      given dietary additives (p<0.05). It may be concluded that the chicks with early
      access to dietary additives showed enhanced immune response and gut development,
      under C. perfringens challenge. The findings of this study shed light on
      managerial and nutritional strategies that could be used to prevent NE in the
      broiler industry without the use of in-feed antibiotics. 

PMID- 25049596
TI  - The Influence of Dietary Calcium and Phosphorus Imbalance on Intestinal NaPi-IIb
      and Calbindin mRNA Expression and Tibia Parameters of Broilers.
AB  - A 2*2 factorial experiment was conducted to study the effect of dietary calcium
      and non-phytate phosphorus (nPP) imbalance on calbindin and NaPi-IIb mRNA levels
      in the small intestine and tibia parameters of broiler chicks. One hundred and
      forty four 1-d-old Arbor Acres male broiler chicks were divided into four
      treatments consisted of six replicates with six chicks each. The two dietary
      calcium levels were 1.10% and 0.60%, and two dietary nPP levels were 0.50% and
      0.27%. Results showed that a high Ca/nPP ratio diet (4.07:1) significantly
      depressed feed intake and weight gain of broilers (p<0.05), but a lower Ca:nPP
      ratio (1.2:1) had no influence (p>0.05). Low-Ca with low-P diet resulted in low
      tibia minerals and tibia breaking strength of broilers, and all the tibia
      parameters were further decreased when the dietary ratio of Ca to P was relative
      higher. Low dietary Ca or P up-regulated the calbindin and NaPi-IIb mRNA
      expression levels. Low Ca with normal P diet up-regulated duodenal calbindin mRNA
      expression level to the greatest extent. Low P with a normal Ca diet
      significantly enhanced NaPi-IIb mRNA expression level to the highest extent.
      These results suggest that the calbindin and NaPi-IIb mRNA expression were
      enhanced by the imbalance between dietary Ca and nPP, and their expression were
      not only influenced by Ca or nPP level, but also the ratio of Ca:nPP. 

PMID- 25049597
TI  - Effects of rearing systems on performance, egg characteristics and immune
      response in two layer hen genotype.
AB  - White (Lohmann LSL) and Brown (ATAK-S) laying hens, were reared under organic and
      conventional cage rearing systems, and the effects of the rearing system on
      performance parameters, egg production, egg characteristics, and immune response
      were investigated. For this purpose, a total of 832 laying hens of two commercial
      hybrids, i.e., 416 white (Lohmann LSL) and 416 Brown (ATAK-S) layers, were used.
      The experiment lasted between 23 and 70 wk of age. In this study, the white
      layers yielded more eggs as compared to the brown layers in both organic and
      conventional production systems. Egg weight exhibited a similar pattern to that
      of laying performance. However, the total hen-housed egg number for the white
      birds in the organic system was fewer than that of white birds in the
      conventional cage facility; conversely, a contradictory tendency was observed for
      the brown birds. Livability of the white layers in the organic system was
      remarkably lower (14%) than that of the brown line, whereas the white line
      survived better (3.42%) than their brown counterparts in conventional cages. The
      feed conversion ratio of the white hens was markedly inferior in the organic
      system as compared to that of the white hens in the conventional system, whereas
      relatively lower deterioration was reported in brown layers when reared in an
      organic system. The organic production system increased egg albumen height and
      the Haugh unit in eggs of the brown layers. The yolk color score of organic eggs
      was lower than that of conventional eggs for both brown and white hens. The egg
      yolk ratio of eggs from white layers was found to be higher in organic eggs as
      compared to those obtained in the conventional system. All organic eggs had
      heavier shells than those produced in the conventional system. Eggs from brown
      layers had more protein content than eggs from white layers. Neither housing
      systems nor genotype influenced egg yolk cholesterol concentration. When compared
      to conventional eggs, n-3 fatty acid content was lower in organic eggs, and the n
      6:n-3 ratio was higher in organic eggs. In conclusion, two hen genotypes showed
      different responses in terms of performance and egg quality to two different
      rearing systems. A commercial white strain produced more eggs with higher egg
      quality as compared to a native brown strain. The brown strain was found to have
      adapted well to organic production conditions when survival and total egg number
      was taken into consideration. 

PMID- 25049598
TI  - Forsythia suspensa Extract Has the Potential to Substitute Antibiotic in Broiler
      Chicken.
AB  - Two experiments were conducted to investigate the potential for Forsythia
      suspensa extract (FSE) to substitute for antibiotic in broiler chicken. First, a
      well-diffusion assay procedure and a 2-fold dilution method were used to
      determine the bacteriostatic activity of FSE on Escherichia coli K88,
      staphylococcus aureus, and salmonella was assayed. An inhibitory effect of FSE
      was observed on the growth of these bacteria. This effect seems to be dose
      depended, which disappeared after 25.00, 12.50, 1.56 mg/ml. Second, a 42-d trial
      with 252 broiler chickens (d 1, 38.7+/-1.1 g BW) was conducted to evaluate the
      effect of dietary supplementation of FSE in broiler chicken. The feeding program
      consisted of a starter diet from d 1 to 21 and a finisher diet from d 22 to 42.
      Dietary treatments included were: i) NC: negative control fed a corn-soybean meal
      based diet; ii) PC: positive control group fed based diet with chlortetracycline;
      and iii) FC: a test group fed with 100 mg FSE/kg diet. In this study growth
      performance did not differ among treatments during the starter period. However,
      dietary supplemental chlortetracycline and FSE increased (p<0.05) average daily
      gain (ADG), average daily feed intake (ADFI) compared with NC during the finisher
      and overall phase. Apparent digestibility of calcium on d 21, digestibility of
      energy and calcium on d 42 of FC was greater (p<0.05) than NC. Moreover, cecal
      Escherichia coli counts for birds from FC were lower (p<0.05) than NC. Dietary
      FSE supplementation also improved (p<0.05) villus height and villus height to
      crypt depth ratios in both duodenum and ileum and decreased (p<0.05) crypt depth
      in the duodenum. Duodenum villus height and villus height to crypt depth ratio in
      both duodenum and ileum from the FC group were also greater (p<0.05). Serum
      growth hormone and IGF-1 were not influenced by different treatments. Apparently,
      FSE has the potential to substitute for antibiotic in broiler chicken. 

PMID- 25049599
TI  - Effects of Dietary Garlic Extract on Growth, Feed Utilization and Whole Body
      Composition of Juvenile Sterlet Sturgeon (Acipenser ruthenus).
AB  - This study was carried out to investigate the supplemental effects of dietary
      garlic extract (GE) on growth performance of juvenile sterlet sturgeon (Acipenser
      ruthenus). The first experiment was designed to determine the optimum levels of
      garlic extract as growth promoter during 10 weeks. Three groups (two
      replicates/group) of 240 fish with mean body weight of 85 g were fed with diets
      containing 0 (control), 0.5 and 1.0% of GE. The highest weight gain (%) and feed
      efficiency (%) were found in fish groups fed with diet containing 0.5% GE.
      Subsequently, the supplemental effects of dietary GE was studied on growth of
      juvenile sterlet sturgeon (Acipenser ruthenus) with an average body weight of
      59.6 g. Fish cultured in freshwater were randomly allotted to each of 10 tanks
      (two groups of five replicates, 20 fish/tank) and fed diets with 0.5% GE or
      without GE (control), respectively, at the level of 2.0% of fish body weight per
      day for 5 weeks. Weight gain (51.1%), feed efficiency (79.1%), specific growth
      rate (1.18%) and protein efficiency ratio (1.50) of fish fed 0.5% GE were
      significantly (p<0.05) higher than those fish fed the control diet. Significantly
      higher protein (PRE 20.4%) and lipid retention efficiencies (LRE, 74.5%) were
      also found in 0.5% GE group (p<0.05). The present results suggested that dietary
      GE could improve growth and feed utilization of juvenile sterlet sturgeons. 

PMID- 25049600
TI  - Free range hens use the range more when the outdoor environment is enriched.
AB  - To evaluate the role of using forage, shade and shelterbelts in attracting birds
      into the range, three trials were undertaken with free range layers both on a
      research facility and on commercial farms. Each of the trials on the free range
      research facility in South Australia used a total of 120 laying hens (Hyline
      Brown). Birds were housed in an eco-shelter which had 6 internal pens of equal
      size with a free range area adjoining the shelter. The on-farm trials were
      undertaken on commercial free range layer farms in the Darling Downs in Southeast
      Queensland with bird numbers on farms ranging from 2,000-6,800 hens. The first
      research trial examined the role of shaded areas in the range; the second trial
      examined the role of forage and the third trial examined the influence of
      shelterbelts in the range. These treatments were compared to a free range area
      with no enrichment. Aggressive feather pecking was only observed on a few
      occasions in all of the trials due to the low bird numbers housed. Enriching the
      free range environment attracted more birds into the range. Shaded areas were
      used by 18% of the hens with a tendency (p = 0.07) for more hens to be in the
      paddock. When forage was provided in paddocks more control birds (55%) were
      observed in the range in morning than in the afternoon (30%) while for the forage
      treatments 45% of the birds were in the range both during the morning and
      afternoon. When shelterbelts were provided there was a significantly (p<0.05)
      higher % of birds in the range (43% vs. 24%) and greater numbers of birds were
      observed in areas further away from the poultry house. The results from the on
      farm trials mirrored the research trials. Overall 3 times more hens used the
      shaded areas than the non shaded areas, with slightly more using the shade in the
      morning than in the afternoon. As the environmental temperature increased the
      number of birds using the outdoor shade also increased. Overall 17 times more
      hens used the shelterbelt areas than the control areas, with slightly more using
      the shelterbelts in the afternoon than in the morning. Approximately 17 times
      more birds used the forage areas compared to the control area in the
      corresponding range. There were 8 times more birds using a hay bale enriched area
      compared to the area with no hay bales. The use of forage sources (including hay
      bales) were the most successful method on-farm to attract birds into the range
      followed by shelterbelts and artificial shade. Free range egg farmers are
      encouraged to provide pasture, shaded areas and shelterbelts to attract birds
      into the free range. 

PMID- 25049601
TI  - Simple spot method of image analysis for evaluation of highly marbled beef.
AB  - The simple method of evaluating highly marbled beef was examined by image
      analysis. The images of the cross section at the 6 to 7th rib were obtained from
      82 carcasses of Wagyu cattle. By using an overall trace method, the surrounding
      edges of the longissimus thoracis and three muscles were traced automatically and
      manually with image analysis. In a spot method, 3 to 5 locations (2.5 or 3.0 cm
      in diameter) for each muscle were rapidly selected with no manual trace. The
      images were flattened, binarized, and the ratio of fat area to muscle area was
      determined. The correlation coefficients for marbling between different muscles,
      and between the overall trace and the spot methods were 0.55 to 0.81 between
      different muscles and 0.89 to 0.97, respectively. These results suggested that
      the simple spot method is speedy and almost as useful as the overall trace method
      as a measuring technique for beef marbling in loin muscles, especially for highly
      marbled beef. 

PMID- 25049602
TI  - Vitamin C nutrition in cattle.
AB  - Domestic animals, including ruminants, can synthesize vitamin C (VC) in their
      liver; as such, the dietary requirement for VC has not been confirmed in these
      animals. The adequacy of VC has been evaluated by quantifying VC levels in
      plasma, but the reported values in bovine plasma have been widely variable.
      Plasma VC concentration is decreased by heat stress, hepatic lesions, fattening,
      and infectious diseases such as mastitis in cattle. Therefore, VC supplementation
      is potentially beneficial for cattle with low plasma VC concentration. This
      review discusses the methods for determination of plasma VC concentration in
      cattle, VC nutrition, and the efficacy of VC supplementation in calves, dairy
      cattle, and beef cattle. Additionally I propose a reference range for plasma VC
      concentration in Japanese Black cattle. 

PMID- 25049603
TI  - Molecular Characterization and Expression Pattern of Gene IGFBP-5 in the Cashmere
      Goat (Capra hircus).
AB  - Insulin-like growth factor-binding protein-5 (IGFBP-5) is one of the six members
      of IGFBP family, important for cell growth, apoptosis and other IGF-stimulated
      signaling pathways. In order to explore the significance of IGFBP-5 in cells of
      the Inner Mongolian Cashmere goat (Capra hircus), IGFBP-5 gene complementary DNA
      (cDNA) was amplified by reverse transcription polymerase chain reaction (RT-PCR)
      from the animal's fetal fibroblasts and tissue-specific expression analysis was
      performed by semi-quantitative RT-PCR. The gene is 816 base pairs (bp) in length
      and includes the complete open reading frame, encoding 271 amino acids (GenBank
      accession number JF720883). The full cDNA nucleotide sequence has a 99% identity
      with sheep, 98% with cattle and 95% with human. The amino acids sequence shares
      identity with 99%, 99% and 99%, respectively. The bioinformatics analysis showed
      that IGFBP-5 has an insulin growth factor-binding protein homologues (IB) domain
      and a thyroglobulin type-1 (TY) domain, four protein kinase C phosphorylation
      sites, five casein kinase II phosphorylation sites, three prenyl group binding
      sites (CaaX box). The IGFBP-5 gene was expressed in all the tested tissues
      including testis, brain, liver, lung, mammary gland, spleen, and kidney,
      suggesting that IGFBP-5 plays an important role in goat cells. 

PMID- 25049604
TI  - Identification of Candidate Genes Associated with Beef Marbling Using QTL and
      Pathway Analysis in Hanwoo (Korean Cattle).
AB  - Marbling from intramuscular fat is an important trait of meat quality and has an
      economic benefit for the beef industry. Quantitative trait loci (QTL) fine
      mapping was performed to identify the marbling trait in 266 Hanwoo steers using a
      10K single nucleotide polymorphism panel with the combined linkage and linkage
      disequilibrium method. As a result, we found nine putative QTL regions for
      marbling: three on BTA6, two on BTA17, two on BTA22, and two on BTA29. We
      detected candidate genes for marbling within 1 cM of either side of the putative
      QTL regions. Additionally, to understand the functions of these candidate genes
      at the molecular level, we conducted a functional categorization using gene
      ontology and pathway analyses for those genes involved in lipid metabolism or fat
      deposition. In these putative QTL regions, we found 95 candidate genes for
      marbling. Using these candidate genes, we found five genes that had a direct
      interaction with the candidate genes. We also found SCARB1 as a putative
      candidate gene for marbling that involves fat deposition related to cholesterol
      transport. 

PMID- 25049605
TI  - Construction of fat1 Gene Expression Vector and Its Catalysis Efficiency in
      Bovine Fetal Fibroblast Cells.
AB  - The FAT-1 protein is an n-3 fatty acid desaturase, which can recognize a range of
      18- and 20-carbon n-6 substrates and transform n-6 polyunsaturated fatty acids
      (PUFAs) into n-3 PUFAs while n-3 PUFAs have beneficial effect on human health.
      Fat1 gene is the coding sequence from Caenorhabditis elegans which might play an
      important role on lipometabolism. To reveal the function of fat1 gene in bovine
      fetal fibroblast cells and gain the best cell nuclear donor for transgenic
      bovines, the codon of fat1 sequence was optimized based on the codon usage
      frequency preference of bovine muscle protein, and directionally cloned into the
      eukaryotic expression vector pEF-GFP. After identifying by restrictive enzyme
      digests with AatII/XbaI and sequencing, the fusion plasmid pEF-GFP-fat1 was
      identified successfully. The pEF-GFP-fat1 vector was transfected into bovine
      fetal fibroblast cells mediated by Lipofectamine2000(TM). The positive bovine
      fetal fibroblast cells were selected by G418 and detected by RT-PCR. The results
      showed that a 1,234 bp transcription was amplified by reverse transcription PCR
      and the positive transgenic fat1 cell line was successfully established. Then the
      expression level of fat1 gene in positive cells was detected using quantitative
      PCR, and the catalysis efficiency was detected by gas chromatography. The results
      demonstrated that the catalysis efficiency of fat1 was significantly high, which
      can improve the total PUFAs rich in EPA, DHA and DPA. Construction and expression
      of pEF-GFP-fat1 vector should be helpful for further understanding the mechanism
      of regulation of fat1 in vitro. It could also be the first step in the production
      of fat1 transgenic cattle. 

PMID- 25049606
TI  - Growth of Ovarian Primary Follicles Retrieved from Neonates of Different Ages and
      Derivation of Mature Oocytes Following In vitro-Culture.
AB  - This study was conducted to improve the yield of mature oocytes from in vitro
      culture of ovarian primary follicles by optimizing follicle retrieval from
      neonatal mice of different ages. Primary follicles of 75 to 99 MUm in diameter
      were collected daily from 7- to 14-day-old neonatal mice, and subsequently
      cultured in alpha-MEM medium. Number of primary follicles isolated, growth of the
      follicle during in vitro-culture and maturation of intrafollicular oocytes were
      monitored. Overall, mean number of preantral follicles per animal was improved
      from 10.7 to 88.7 as the age of follicle donors was increased from 7 to 14-day
      old. Number of primary follicles was increased gradually up to 11-day-old (35.7
      follicle per an animal), then reduced to 29 in 14-day-old (p = 0.0013). More
      follicles retrieved from 10-day-old or 11-day-old females maintained their
      morphological normality at the end of primary culture than the follicles
      retrieved from 9-day-old. Of those cultured, primary follicles retrieved from 11
      day-old mice yielded largest larger number of early secondary follicles than the
      follicles retrieved from in the other ages (39 vs. 13 to 29%). More than 3.3
      times increase (0.86 to 2.86; p<0.05) in an average number of mature oocytes per
      animal was observed in the group of 11-day-old, compared with 9-day-old. However,
      no difference was found in the percentage of primary follicles developing into
      the pseudoantral stage (21 to 30%; p = 0.5222) and in the percentage of oocytes
      mucified (32 to 39%; p = 0.5792). In conclusion, a positive correlation between
      retrieval time and follicle growth was detected, which influences the efficiency
      to derive mature oocytes by follicle culture. 

PMID- 25049607
TI  - Induction of Ski Protein Expression upon Luteinization in Rat Granulosa Cells.
AB  - Ski protein is implicated in proliferation/differentiation in a variety of cells.
      We had previously reported that Ski protein is present in granulosa cells of
      atretic follicles, but not in preovulatory follicles, suggesting that Ski has a
      role in apoptosis of granulosa cells. The alternative fate of granulosa cells
      other than apoptosis is to differentiate to luteal cells; however, it is unknown
      whether Ski is expressed and has a role in granulosa cells undergoing
      luteinization. Thus, the aim of the present study was to locate Ski protein in
      the rat ovary during luteinizationto predict the possible role of Ski. In order
      to examine the expression pattern of Ski protein along with the progress of
      luteinization, follicular growth was induced by administration of equine
      chorionic gonadtropin to immature female rats, and luteinization was induced by
      human chorionic gonadtropin treatment to mimic luteinizing hormone (LH) surge.
      While no Ski-positive granulosa cells were present in preovulatory follicle, Ski
      protein expression was induced in response to LH surge, and was maintained after
      the formation of the corpus luteum (CL). Though Ski protein is absent in
      granulosa cells of preovulatory follicle, its mRNA (c-Ski) was expressed and the
      level was unchanged even after LH surge. Taken together, these results
      demonstrated that Ski protein expression is induced in granulosa cells upon
      luteinization, and suggests that its expression is regulated post
      transcriptionally. 

PMID- 25049608
TI  - Effects of two halophytic plants (kochia and atriplex) on digestibility,
      fermentation and protein synthesis by ruminal microbes maintained in continuous
      culture.
AB  - Eight continuous culture fermenters were used in a completely randomized design
      to evaluate various nutritional values of Kochia (Kochia scoparia) compared with
      Atriplex (Atriplex dimorphostegia). Dried and pelleted samples (leaves and stems)
      provided substrate for metabolism by ruminal microbes maintained in a continuous
      culture fermentation system. Results indicated that there were no differences
      (p>0.05) in dry matter (DM) and crude protein (CP) digestibility between the two
      halophytic plants. Atriplex had higher (p<0.05) organic matter (OM) digestibility
      compared with Kochia. Neutral detergent fiber (aNDF) digestibility of Atriplex
      (411 g/kg) was higher (p<0.05) than that of Kochia (348 g/kg), however acid
      detergent fiber (ADF) digestibility was higher (p<0.05) in Kochia compared with
      Atriplex (406 vs. 234 g/kg). There were no differences (p>0.05) between the two
      halophytic plants in molar proportion of acetate and propionate, but the
      concentration of butyrate and valerate in Kochia were about two fold of Atriplex
      (p<0.05). When Kochia provided substrate to the microbes, protein synthesis was
      higher (p<0.05) compared with feeding Atriplex (5.96 vs. 4.85 g N/kg of OM truly
      digested). It was concluded that Kochia scoparia and Atriplex dimorphostegia had
      similar digestibility of DM and CP. It appears that these halophytic plants may
      not have enough digestible energy for high producing ruminants. 

PMID- 25049609
TI  - Fatty Acid Profiles and Stearoyl-CoA Desaturase Gene Expression in Longissimus
      dorsi Muscle of Growing Lambs Influenced by Addition of Tea Saponins and Soybean
      Oil.
AB  - This study was conducted to determine the effects of dietary addition of tea
      saponins (TS) and soybean oil (SO) on fatty acid profile and gene expression of
      stearoyl-CoA desaturase (SCD) in longissimus dorsi (LD) muscle of growing lambs.
      Thirty-two Huzhou lambs were assigned to four dietary treatments in a 2*2
      factorial arrangement with main effects of TS (0 or 3 g/d) and SO (0 or 30 g/kg
      of diet DM). The diet without additives was considered as NTNS (no TS or SO).
      After a feeding trial for 60 d, four lambs of each treatment were slaughtered to
      collect the samples of LD muscle. Percentage of trans-11 vaccenic acid was
      enhanced (p<0.05) in muscle of lambs fed TS and SO. The proportion of total
      conjugated linoleic acid (CLA) was increased (p<0.05) by SO, but decreased
      (p<0.05) by TS in LD muscle. The percentage of total saturated fatty acids in
      muscle was decreased (p<0.05) by addition of TS and SO, while addition of SO
      increased (p<0.05) the percentage of total polyunsaturated fatty acids. The ratio
      of cis-9, trans-11 CLA to tran-11 vaccenic acid was decreased (p<0.05) by TS, but
      increased (p<0.05) by SO. The same effects were observed in SCD mRNA expression.
      From these results it is indicated that including TS and SO in the diet of
      growing lambs affect the fatty acid profiles of LD muscle and that the proportion
      of cis-9, trans-11 CLA in the muscle influenced by TS and SO may be related to
      the SCD gene expression. 

PMID- 25049611
TI  - Effects of feeding methylthio butyric Acid isopropyl ester on postpartum
      performance and metabolism in dairy cows.
AB  - The present experiment aimed to evaluate the effect of HMBi on the production
      performance and metabolism in dairy cows. Thirty multiparous Holstein dairy cows
      under similar conditions were randomly assigned to three dietary treatments; i)
      Control, a basal diet; ii) T1, a basal diet plus HMBi (0 g prepartum and 18 g
      postpartum); and iii) T2, a basal diet plus HMBi (10 g prepartum and 18 g
      postpartum). Treatments were initiated 21 d before expected calving and continued
      through 91 d postpartum. HMBi was top-dressed onto the total mixed ration of each
      cow. Treatments did not affect dry matter intake, plasma urea nitrogen, peak milk
      yield, days to peak milk yield, nonesterified fatty acid, glutamate pyruvate
      transaminase, glutamic oxalaetic transaminase, milk fat content, milk protein
      content, milk lactose content, and milk solid non-fat content. The milk
      composition yields were increased by the HMBi-supplemented treatment. The T1 and
      T2 treatments increased the yields of 4% fat-corrected milk yield, milk fat, milk
      protein, and milk lactose compared with the control. Although there was no
      difference in the milk composition of the control and T2-treated cows, the T2
      treated cows exhibited higher milk fat yield (increased by 74 g/d), lower milk
      urea nitrogen (reduced by 3.41%), and plasma beta-hydroxy butyrate than the
      control cows. The results indicate that HMBi supplementation to diet has
      beneficial effects, and that there is no difference between supplementation at
      prepartum and starting only at parturition. 

PMID- 25049610
TI  - Effects of dietary potential Acid production value on productivity in dairy cows.
AB  - This study was conducted to estimate the potential acid production value (PAPV)
      of major diets and to determine the relationship between dietary PAPV and dairy
      production traits. Estimation of PAPV of major cattle feeds was based on an in
      vitro technique, which determined the degree of Ca dissociation from CaCO3. Data
      on feeds and production traits were collected on 744 multiparous lactating
      Holstein dairy cows from five different farms. Grains had high PAPV with variable
      protein sources and by-products. High PAPV feedstuffs had a higher total gas
      production and lower pH compared to those with low PAPV. Dietary PAPV had a
      positive correlation with intake of dry matter, NDF, ADF, milk yield and milk
      solid production but a negative correlation with milk protein and milk fat
      concentration. Current results indicate that dietary PAPV can be utilized in
      predicting dairy production traits. 

PMID- 25049612
TI  - Combination of an Enzymatically Hydrolyzed Yeast and Yeast Culture with a Direct
      fed Microbial in the Feeds of Broiler Chickens.
AB  - A balance trial experiment was carried out to evaluate the potential relationship
      between an enzymatically hydrolyzed yeast (EHY) and yeast culture combined with a
      live Bacillus subtilis (Bs) on the productive parameters, ileal digestibility,
      retention of nutrient and energy and villus morphology in broilers. Seventy two
      28 d old, Ross B308 male broilers were assigned to a factorial combination of 2
      levels of EHY (0 and 1 kg/ton of feed) and 2 levels of Bs (0 and 125 g/ton of
      feed). The experiment lasted 2 weeks. Several treatment interactions were
      observed. EHY-fed broilers showed the lowest feed intake and feed conversion
      ratio whereas Bs-fed broilers showed the highest feed intake and intermediate
      feed conversion ratio (EHY and BS interaction, p<0.05). Also, EHY-fed broilers
      had greater ileal digestibility of dry matter (EHY and BS interaction, p<0.01)
      and energy (EHY and BS interaction, p<0.05) but these responses were
      counterbalanced by the combination of EHY and Bs. The thickness of the mucosa was
      similar between the control and EHY-fed broilers, but was lowest when Bs was
      added alone (EHY and BS interaction, p<0.01). The thickness of the villus was
      greater in EHY plus Bs-fed broilers, intermediate for the control and lower for
      Bs or EHY-fed broilers (EHY and BS interaction, p<0.05). The area of the villus
      was greater in the control and EHY plus Bs-fed broilers (EHY and BS interaction,
      p<0.05). In addition, EHY-fed broilers showed greater breast yield and nitrogen
      retention (p<0.01) and ashes digestibility (p<0.05). On the other hand, Bs-fed
      broilers had greater carcass and breast weight, nitrogen retention, energy
      excretion and villus height (p<0.05). In summary, EHY and Bs enhanced some
      growth, carcass and nutrient retention responses, but did not show any synergic
      relationship in these responses. Opposite to this, the results suggest that the
      positive effect of EHY on the feed conversion and digestibility of nutrients were
      counterbalanced by the addition of Bs. 

PMID- 25049613
TI  - Effects of supplemental glutamine on growth performance, plasma parameters and
      LPS-induced immune response of weaned barrows after castration.
AB  - Two experiments were conducted to investigate the effects of supplemental
      glutamine on growth performance, plasma parameters and LPS-induced immune
      response of weaned barrows after castration. In experiment 1, forty-eight weaned
      male piglets were used and fed maize and soybean meal diets supplemented with 0
      (Control) or 2% L-Gln (Gln+) for 25 days. The results indicated that the Gln+
      group tended to increase average daily gain compared to control in stages of days
      7 to 14 and 0 to 25. The Gln+ had significantly better feed efficiency than the
      control group did during days 14 to 25 and 0 to 25. The plasma blood urea
      nitrogen and alkaline phosphatase contents of Gln+ group were higher than those
      of the control group on day 14 post-weaning. In experiment 2, sixteen weaned male
      piglets were injected with E. coli K88+ lipopolysaccharide (LPS) on day 14 post
      weaning. The results showed that the Gln+ group had lower concentrations of
      plasma adrenocorticotrophic hormone and cortisol than the control group on day 14
      pre-LPS challenge. In addition, Gln+ group had higher plasma IgG concentration
      than the control group for pre- or post-LPS challenged on day 14 post-weaning. In
      summary, dietary supplementation of Gln was able to alleviate the stressful
      condition and inflammation associated with castration in weaned barrows, and to
      improve their immunity and growth performance in the early starter stage. 

PMID- 25049614
TI  - Growth Performance and Meat Quality of Broiler Chickens Supplemented with
      Bacillus licheniformis in Drinking Water.
AB  - A feeding trial was conducted to investigate effects of Bacillus licheniformis on
      growth performance and meat quality of broilers. Nine hundred one-d-old broiler
      chicks were randomly assigned to 3 experimental groups with three replicate pens
      of 100 broiler chicks. Three treatments were i) control, ii) basal diets
      supplemented with 1 ml of B. licheniformis for each in feed water per day iii)
      basal diets supplemented with 2 ml of B. licheniformis per chick in feed water
      per day. The supplementation of B. licheniformis significantly increased body
      weight in grower chickens (p<0.05), and significantly improved the feed
      conversion in 3 to 6 and 0 to 6 wk feeding period compared with the control group
      (p<0.05). Additionally, the supplement also resulted in increased protein and
      free amino acid contents, and decreased fat content in chicken breast fillet
      (p<0.05). Furthermore, improvement in sensory attributes was observed in broilers
      fed with the probiotic. In conclusion, B. licheniformis treatments resulted in a
      significant increase (p<0.05) in broiler productivity based on an index taking
      into account daily weight gain and feed conversion rate. Meanwhile, the probiotic
      contributed towards an improvement of the chemical, nutritional and sensorial
      characteristics of breast fillet. Overall, the study indicates that B.
      licheniformis can be used as a growth promoter and meat quality enhancer in
      broiler poultry. 

PMID- 25049615
TI  - Bacterial Community Dynamics during Swine In vitro Fermentation Using Starch as a
      Substrate with Different Feed Additives for Odor Reduction.
AB  - The experiment was conducted by in vitro fermentation and bacterial community
      analysis to investigate the reduction of odorous compounds in response to the use
      of feed additives (FA) during carbohydrate overload in growing pigs. Soluble
      starch at 1% (control) and various FA at 0.1% Ginseng meal (FA1); Persimmon leaf
      (FA2); Gingko nut (FA3) and Oregano lippia (FA4) were added to fecal slurry and
      incubated anaerobically for 12 and 24 h. In vitro parameters and microbial
      diversity of the dominant bacteria following fermentation were analyzed using
      Denaturing Gradient Gel Electrophoresis (DGGE), band cloning and sequencing of
      the V3 region. Results showed that total gas production increased with the
      advancement of incubation (p<0.05). pH values of FAs and control groups were
      decreased except the FA4 group which increased somewhat from 12 to 24 h (p<0.05).
      Ammonia nitrogen (NH3-N) and H2S gas concentrations were comparatively lower in
      both stages in FA4 treatment than in the other groups (p<0.05). Hence, NH3-N
      concentrations in liquid phases were increased (p<0.05) from 12 to 24 h, but the
      trend was lowest in FA4 than in the other groups at both stages. The total VFA
      production was comparatively lower and butyrate levels were moderate in FA4 group
      than in the the other groups during both stages (p<0.05). Indirect odor-reducing
      compounds such as NO2, NO3 and SO4 concentrations were higher in the FA4 and FA3
      than in the other groups at 24 h (p<0.05). After fermentation, ten dominant bands
      appeared, six of which appeared in all samples and four in only the FA4 treated
      group. The total number of DGGE bands and diversity was higher in the FA4-group
      compared to other groups. Additionally, similarity indices were lowest (71%) in
      the FA4, which represented a different bacterial community compared with the
      other groups. These findings indicate that NH3-N, H2S and VFA production was
      minimal, and pH was also better in the FA4 group than in the other groups.
      Furthermore, the conversion of odor-reducing indirect compounds or their
      intermediates was higher in the FA4 group in compared to the other groups. FA4
      group generated less odorous products and more indirect products by in vitro
      fermentation at 24 h, and their microbial pattern appeared to differ from that of
      the other groups. These findings suggest that this particular FA could change the
      microbial population, which may have a beneficial effect on odor reduction. It is
      recommended that the oregano lippia may be supplied to growing pigs as FA along
      with excess carbohydrate sources to reduce the production of odorous compounds. 

PMID- 25049616
TI  - Effects of immune stress on performance parameters, intestinal enzyme activity
      and mRNA expression of intestinal transporters in broiler chickens.
AB  - Immune stress is the loss of immune homeostasis caused by external forces. The
      purpose of this experiment was to investigate the effects of immune stress on the
      growth performance, small intestinal enzymes and peristalsis rate, and mRNA
      expression of nutrient transporters in broiler chickens. Four hundred and thirty
      two 1-d-old broilers (Cobb500) were randomly assigned to four groups for
      treatment; each group included nine cages with 12 birds per cage. Group 1 = no
      vaccine (NV); Group 2 = conventional vaccine (CV); group 3 = lipopolysaccharide
      (LPS)+conventional vaccine (LPS); group 4 = cyclophosphamide (CYP)+conventional
      vaccine (CYP). The results demonstrated that immune stress by LPS and CYP reduced
      body weight gain (BWG), feed intake (FI), small intestine peristalsis rate and
      sIgA content in small intestinal digesta (p<0.05). However, the feed conversion
      ratio (FCR) remained unchanged during the feeding period. LPS and CYP increased
      intestinal enzyme activity, relative expression of SGLT-1, CaBP-D28k and L-FABP
      mRNAs (p<0.05). LPS and CYP injection had a negative effect on the growth
      performance of healthy broiler chickens. The present study demonstrated that NV
      and CV could improve growth performance while enzyme activity in small intestine
      and relative expression of nutrient transporter mRNA of NV and CV were decreased
      in the conditions of a controlled rational feeding environment. It is generally
      recommended that broilers only need to be vaccinated for the diseases to which
      they might be exposed. 

PMID- 25049617
TI  - Red Deer Antler Extract Accelerates Hair Growth by Stimulating Expression of
      Insulin-like Growth Factor I in Full-thickness Wound Healing Rat Model.
AB  - In order to investigate and evaluate the effects of red deer antlers on hair
      growth in the full-thickness wound healing model, Sprague-Dawley rats were given
      incision wounds through the full thickness of their dorsal skin and deer antler
      was applied for 40 days. At specified intervals thereafter (4, 8, 16, 32 and 40
      days), the animals were sacrificed and the wound site skins were excised,
      processed, and sectioned. At post-injury days 16, 32 and 40, longer and more
      active new hair appeared around the healing wound of antler-treated skin.
      Histological studies showed that the antler extract markedly increases the depth,
      size, and number of hair follicles. Expression of IGF-I (insulin-like growth
      factor) mRNA was detected by RT-PCR and real time RT-PCR. The result showed that
      the expression of IGF-I (days 16, 32, and 40) was obviously up-regulated in
      antler-treated skins compared to control skins. Similar results were seen in the
      ELISA analysis to quantify the IGF-I expression. These results support the notion
      that wound healing can cause hair growth by enhancing the expression of IGF-I.
      Deer antler extract appears to have the potential to promote hair growth and
      could be used in hair growth products. 

PMID- 25049618
TI  - General behaviors and perching behaviors of laying hens in cages with different
      colored perches.
AB  - Color is one of the perch properties. This study was conducted to investigate the
      general behaviors and perching behaviors in laying hens under different group
      size (stocking density), and to understand the perch color (black, white or
      brown) preference of hens during the night. A total of 390 Hyline Brown laying
      hens was used, and randomly allocated to three treatments: individual group (G1),
      group of four hens (G4), and group of eight hens (G8), respectively. There were
      30 replicates in each group. The hens in G1, G4 and G8 groups were put into the
      test cages in which three colored perches were simultaneously provided and
      allowed for four days of habituation in the new cages. Hens behaviors were
      recorded using cameras with infrared light sources for the following periods:
      8:00 to 10:00; 14:00 to 16:00; 19:00 to 21:00; 23:30 to 0:30 on the fifth day
      after transferring the birds into the test cages. The behaviors of hens in every
      time period were collected and analyzed, and hens positions on the test perches
      during mid-night were recorded. The results showed that, group size (stocking
      density) had significant effect on most of the general behaviors of laying hens
      except exploring behavior. There were great differences in most of the general
      behaviors during different time periods. In the preference test of perch color
      during night, the hens showed no clear preference for white, black or brown
      perches. For perching behaviors, perching time and frequency of transferring from
      one perch to another was higher on black perches than on white or brown perches
      in individual groups. In G4 groups, the hens spent more time on white perches
      during daytime and more frequent transferring during night compared with black or
      brown perches. The frequency of jumping upon and down from white perches was
      higher in G8 groups. It can be concluded that although the group sizes in the
      cage significantly affected most of the general behaviors, we found that no
      preference of perch color was shown by the caged laying hens in the different
      group sizes tested in this study. 

PMID- 25049619
TI  - Effects of Hydrated Potato Starch on the Quality of Low-fat Ttoekgalbi (Korean
      Traditional Patty) Packaged in Modified Atmosphere Conditions during Storage.
AB  - This study was carried out to investigate the effects of hydrated potato starch
      on the quality of low-fat ttoekgalbi (Korean traditional patty) packaged in
      modified atmosphere conditions during storage. The ttoekgalbi was prepared from
      53.2% lean beef, 13.9% lean pork, 9.3% pork fat, and 23.6% other ingredients. Two
      low-fat ttoekgalbi treatments were prepared by substituting pork fat with
      hydrated potato starch; either by 50% fat replacement (50% FR) or 100% fat
      replacement (100% FR). Both 50% and 100% FR increased the moisture, crude
      protein, and decreased fat content, cooking loss, and hardness. For MAP studies,
      200 g of ttoekgalbi were placed on the tray and filled with gas composed of 70%
      O2: 30% CO2 (70% O2-MAP) and 30% CO2: 70% N2 (70% N2-MAP), and were stored at 5
      degrees C for 12 d. During the storage time, both 50% and 100% FR showed higher
      protein deterioration, while no differences were found in CIE a*, CIE L*, lipid
      oxidation, and bacterial counts in comparison to control. The ttoekgalbi with 70%
      O2-MAP was more red, lighter in color, and showed higher TBARS values compared
      with 70% N2-MAP. The meat with 70% N2-MAP showed lower aerobic bacterial counts
      in control than those with 70% O2-MAP. The lower anaerobic bacterial counts were
      observed only in 50% FR and 100% FR packed with 70% N2-MAP in comparison with 70%
      O2-MAP. In conclusion, the fat replacement with hydrated potato starch showed no
      negative effects on the quality of low fat ttoekgalbi during storage and 70% N2
      MAP was better than 70% O2-MAP for low-fat ttoekgalbi packaging. 

PMID- 25049620
TI  - Sex Determination of Cattle Meat by Polymerase Chain Reaction Amplification of
      the DEAD Box Protein (DDX3X/DDX3Y) Gene.
AB  - Determination of sex origin of cattle meat by fast and reliable molecular methods
      is an important measure to ensure correct allocation of export refunds
      particularly in European countries and also female cattle (cow) slaughter is
      legally banned in India because of religious beliefs. Based on the DEAD box
      protein gene located on the X and Y chromosomes, 2 pair of primers were designed
      and the system of PCR was optimized. Upon PCR amplification, male tissue showed 2
      bands, while female tissue resulted in only one band. The accuracy and
      specificity of the primers was assessed using DNA template extracted from cattle
      meat of known sex. The protocol was subjected to a blind test and showed 100%
      concordance, proving its accuracy and reliability. 

PMID- 25049621
TI  - Management of reproduction on small, medium and large rabbit farms: a review.
AB  - One of the main goals of small, medium and large farms is to improve the
      reproductive performance of rabbit does. Stocks of lower productivity can be
      improved by crossing with intensive breeds. A better nutritional status of both
      foetuses and suckling kits has a positive effect on their later productivity.
      Overfeeding young females before first mating can lead to conditions of
      fattiness. Using restricted feeding or higher fibre content in the feed and
      changing it for a higher level ad libitum feeding about one week prior to first
      mating leads to longer lifespan and higher productive level. Intensive
      reproductive rhythm creates a negative energy balance in does : they are unable
      to consume enough feed (energy) for the nutritional requirements of foetus and
      lactation, and therefore lose most of their fat reserves. Furthermore,
      primiparous does also expend energy because they are still growing. Under
      intensive conditions, the 42-d reproductive rhythm (re-mating 11 days after
      parturition) is recommended. Under extensive conditions, the 18 or 25-d mating
      interval with 35 to 42-d weaning could be suitable. On small farms, natural
      mating is favoured; on large farms AI is commonly employed. The main advantage of
      AI is the all-in, all-out system. Hormonal (PMSG) treatment is used with AI to
      increase receptivity on d 11. Frequent and high level PMSG use can lead to higher
      anti-PMSG antibody rates. Lower level (max. 20 IU) and less frequent PMSG
      injection or non-hormonal alternative methods (short dam-litter separation,
      changing nursing method or lighting programs) are recommended for this reason. 

PMID- 25049622
TI  - Molecular Characterization of Selected Local and Exotic Cattle Using RAPD Marker.
AB  - In order to develop specific genetic markers and determine the genetic diversity
      of Bangladeshi native cattle (Pabna, Red Chittagong) and exotic breeds (Sahiwal),
      randomly amplified polymorphic DNA (RAPD) analysis was performed using 12
      primers. Genomic DNA was extracted from 20 cattle (local and exotic) blood
      samples and extracted DNA was observed by gel electrophoresis. Among the random
      primers three were matched and found to be polymorphic. Genetic relations between
      cattle's were determined by RAPD polymorphisms from a total of 66.67%.
      Statistical analysis of the data, estimating the genetic distances between cattle
      and sketching the cluster trees were estimated by using MEGA 5.05 software.
      Comparatively highest genetic distance (0.834) was found between RCC-82 and SL
      623. The lowest genetic distance (0.031) was observed between M-1222 and M-5730.
      The genetic diversity of Red Chittagong and Sahiwal cattle was relatively higher
      for a prescribed breed. Adequate diversity in performance and adaptability can be
      exploited from the study results for actual improvement accruing to conservation
      and development of indigenous cattle resources. 

PMID- 25049623
TI  - Molecular Characterization and Tissue-specific Expression of a Novel FKBP38 Gene
      in the Cashmere Goat (Capra hircus).
AB  - As a member of a subclass of immunophilins, it is controversial that FKBP38 acts
      an upstream regulator of mTOR signaling pathway, which control the process of
      cell-growth, proliferation and differentiation. In order to explore the
      relationship between FKBP38 and mTOR in the Cashmere goat (Capra hircus) cells, a
      full-length cDNA was cloned (GenBank accession number JF714970) and expression
      pattern was analyzed. The cloned FKBP38 gene is 1,248 bp in length, containing an
      open reading frame (ORF) from nucleotide 13 to 1,248 which encodes 411 amino
      acids, and 12 nucleotides in front of the initiation codon. The full cDNA
      sequence shares 98% identity with cattle, 94% with horse and 90% with human. The
      putative amino acid sequence shows the higher homology which is 98%, 97% and 94%,
      correspondingly. The bioinformatics analysis showed that FKBP38 contained a
      FKBP_C domain, two TPR domains and a TM domain. Psite analysis suggested that the
      ORF encoding protein contained a leucine-zipper pattern and a Prenyl group
      binding site (CAAX box). Tissue-specific expression analysis was performed by
      semi-quantitative RT-PCR and showed that the FKBP38 expression was detected in
      all the tested tissues and the highest level of mRNA accumulation was detected in
      testis, suggesting that FKBP38 plays an important role in goat cells. 

PMID- 25049624
TI  - Estimation of genetic parameters from longitudinal records of body weight of
      berkshire pigs.
AB  - Direct and maternal genetic heritabilities and their correlations with body
      weight at 5 stages in the life span of purebred Berkshire pigs, from birth to
      harvest, were estimated to scrutinize body weight development with the records
      for 5,088 purebred Berkshire pigs in a Korean farm, using the REML based on an
      animal model. Body weights were measured at birth (Birth), at weaning (Weaning:
      mean 22.9 d), at the beginning of a performance test (On: mean 72.7 d), at the
      end of a performance test (Off: mean 152.4 d), and at harvest (Finish: mean 174.3
      d). Ordinary polynomials and Legendre with order 1, 2, and 3 were adopted to
      adjust body weight with age in the multivariate animal models. Legendre with
      order 3 fitted best concerning prediction error deviation (PED) and yielded the
      lowest AIC for multivariate analysis of longitudinal body weights. Direct genetic
      correlations between body weight at Birth and body weight at Weaning, On, Off,
      and Finish were 0.48, 0.36, 0.10, and 0.10, respectively. The estimated maternal
      genetic correlations of body weight at Finish with body weight at Birth, Weaning,
      On, and Off were 0.39, 0.49, 0.65, and 0.90, respectively. Direct genetic
      heritabilities progressively increased from birth to harvest and were 0.09, 0.11,
      0.20, 0.31, and 0.43 for body weight at Birth, Weaning, On, Off, and Finish,
      respectively. Maternal genetic heritabilities generally decreased and were 0.26,
      0.34, 0.15, 0.10, and 0.10 for body weight at Birth, Weaning, On, Off, and
      Finish, respectively. As pigs age, maternal genetic effects on growth are reduced
      and pigs begin to rely more on the expression of their own genes. Although
      maternal genetic effects on body weight may not be large, they are sustained
      through life. 

PMID- 25049625
TI  - Optimal Design for Marker-assisted Gene Pyramiding in Cross Population.
AB  - Marker-assisted gene pyramiding aims to produce individuals with superior
      economic traits according to the optimal breeding scheme which involves selecting
      a series of favorite target alleles after cross of base populations and
      pyramiding them into a single genotype. Inspired by the science of evolutionary
      computation, we used the metaphor of hill-climbing to model the dynamic behavior
      of gene pyramiding. In consideration of the traditional cross program of animals
      along with the features of animal segregating populations, four types of cross
      programs and two types of selection strategies for gene pyramiding are performed
      from a practical perspective. Two population cross for pyramiding two genes
      (denoted II), three population cascading cross for pyramiding three genes(denoted
      III), four population symmetry (denoted IIII-S) and cascading cross for
      pyramiding four genes (denoted IIII-C), and various schemes (denoted cross
      program-A-E) are designed for each cross program given different levels of
      initial favorite allele frequencies, base population sizes and trait
      heritabilities. The process of gene pyramiding breeding for various schemes are
      simulated and compared based on the population hamming distance, average superior
      genotype frequencies and average phenotypic values. By simulation, the results
      show that the larger base population size and the higher the initial favorite
      allele frequency the higher the efficiency of gene pyramiding. Parents cross
      order is shown to be the most important factor in a cascading cross, but has no
      significant influence on the symmetric cross. The results also show that
      genotypic selection strategy is superior to phenotypic selection in accelerating
      gene pyramiding. Moreover, the method and corresponding software was used to
      compare different cross schemes and selection strategies. 

PMID- 25049626
TI  - Effect of Peripheral Administration of Kisspeptin-10 on Dynamic LH Secretion in
      Prepubertal Ewes.
AB  - The aim of the present study was to clarify the effect of kisspeptin-10 on LH
      secretion in prepubertal ewes. In experiment 1, prepubertal ewes fitted with
      indwelling jugular catheters were randomly assigned to receive 0, 0.5, 1 or 2 mg
      of kisspeptin-10 dissolved in saline, and serial blood samples were collected at
      15-min intervals for 180 min to analyze the response curves of LH after
      injection. In experiment 2, prepubertal ewes fitted with indwelling jugular
      catheters were injected with 0 or 1 mg of kisspeptin-10 dissolved in saline and
      the injection was repeated 3 times at 1 h interval and serial blood samples were
      collected at 15-min intervals for 210 min to analyze the response curves of LH
      after injection. The results showed that single intravenous administration of
      0.5, 1 and 2 mg of kisspeptin-10 all could significantly increased LH secretion
      in prepubertal ewes, and the effect of 1 and 2 mg of kisspeptin-10 on LH
      secretion was higher than that of 0.5 mg group. The results also showed that
      repeated intravenous administration of kisspeptin-10 could effectively increase
      LH secretion and repeated administration did not influence the effect of
      kisspeptin-10 on LH secretion in prepubertal ewe. In conclusion, the present
      study indicated that single or repeated intravenous administration of kisspeptin
      10 could effectively increase LH secretion in prepubertal ewes. 

PMID- 25049627
TI  - Phosphorylation Status of RNA Polymerase II Carboxyl-terminal Domain in Porcine
      Oocytes and Early Embryos.
AB  - Fertilization of the oocyte commences embryogenesis during which maternally
      inherited mRNAs are degraded and the embryonic genome is activated. Transcription
      of embryonic mRNA is initiated by embryonic genome activation (EGA). RNA
      polymerase II (RNA Pol II) is responsible for the synthesis of mRNAs and most
      small nuclear RNAs, and consists of 12 subunits, the largest of which
      characteristically harbors a unique C-terminal domain (CTD). Transcriptional
      activity of RNA Pol II is highly regulated, in particular, by phosphorylation of
      serine residues in the CTD. Here, we have shown the presence of RNA Pol II CTD
      phosphoisoforms in porcine oocytes and preimplantation embryos. The distribution
      pattern as well as phosphorylation dynamics in germinal vesicles and during
      embryogenesis differed in developmental stages with these isoforms, indicating a
      role of RNA Pol II CTD phosphorylation at the serine residue in transcriptional
      activation during both oocyte growth and embryonic genome activation. We
      additionally examined the effects of the RNA Pol II inhibitor, alpha-amanitin, on
      embryo development. Our results show that inhibition of polymerase, even at very
      early stages and for a short period of time, dramatically impaired blastocyst
      formation. These findings collectively suggest that the functionality of maternal
      RNA Pol II, and consequently, expression of early genes regulated by this enzyme
      are essential for proper embryo development. 

PMID- 25049628
TI  - Polymorphysims of CYP17-I Gene in the Exons Were Associated with the Reproductive
      Endocrine of Japanese Flounder (Paralichthys olivaceus).
AB  - The cytochrome P450c17-I (CYP17-I) is one of the enzymes critical to gonadal
      development and the synthesis of androgens. Two single nucleotide polymorphisms
      (SNPs) were detected within the coding region of the CYP17-I gene in a population
      of 75 male Japanese flounder (Paralichthys olivaceus). They were SNP1 (c.C445T)
      located in exon2 and SNP2 (c.T980C (p.Phe307Leu)) located in exon5. Four
      physiological indices, which were serum testosterone (T), serum 17beta-estradiol
      (E2), Hepatosomatic index (HSI), and Gonadosomatic index (GSI), were studied to
      examine the effect of the two SNPs on the reproductive endocrines of Japanese
      flounder. Multiple comparisons revealed that CT genotype of SNP1 had a much lower
      T level than CC genotype (p<0.05) and the GSI of individuals with CC genotype of
      SNP2 was higher than those with TT genotype (p<0.05). Four diplotypes were
      constructed based on the two SNPs and the diplotype D3 had a significantly lower
      T level and GSI. In conclusion, the two SNPs were significantly associated with
      reproductive traits of Japanese flounder. 

PMID- 25049629
TI  - Mutation of cellulose synthase gene improves the nutritive value of rice straw.
AB  - Rice straw is an important roughage resource for ruminants in many rice-producing
      countries. In this study, a rice brittle mutant (BM, mutation in OsCesA4,
      encoding cellulose synthase) and its wild type (WT) were employed to investigate
      the effects of a cellulose synthase gene mutation on rice straw morphological
      fractions, chemical composition, stem histological structure and in situ
      digestibility. The morphological fractions investigation showed that BM had a
      higher leaf sheath proportion (43.70% vs 38.21%, p<0.01) and a lower leaf blade
      proportion (25.21% vs 32.14%, p<0.01) than WT. Chemical composition analysis
      showed that BM rice straw was significantly (p<0.01) higher in CP (crude
      protein), hemicellulose and acid insoluble ash (AIA) contents, but lower in dry
      matter (DM), acid detergent fiber (ADFom) and cellulose contents when compared to
      WT. No significant difference (p>0.05) was detected in neutral detergent fiber
      (NDFom) and ADL contents for both strains. Histological structure observation
      indicated that BM stems had fewer sclerenchyma cells and a thinner sclerenchyma
      cell wall than WT. The results of in situ digestion showed that BM had higher DM,
      NDFom, cellulose and hemicellulose disappearance at 24 or 48 h of incubation
      (p<0.05). The effective digestibility of BM rice straw DM and NDFom was greater
      than that of WT (31.4% vs 26.7% for DM, 29.1% vs 24.3% for NDFom, p<0.05), but
      the rate of digestion of the slowly digested fraction of BM rice straw DM and NDF
      was decreased. These results indicated that the mutation in the cellulose
      synthase gene could improve the nutritive value of rice straw for ruminants. 

PMID- 25049630
TI  - Effects of Plant Extracts on Microbial Population, Methane Emission and Ruminal
      Fermentation Characteristics in In vitro.
AB  - This study was conducted to evaluate effects of plant extracts on methanogenesis
      and rumen microbial diversity in in vitro. Plant extracts (Artemisia princeps
      var. Orientalis; Wormwood, Allium sativum for. Pekinense; Garlic, Allium cepa;
      Onion, Zingiber officinale; Ginger, Citrus unshiu; Mandarin orange, Lonicera
      japonica; Honeysuckle) were obtained from the Plant Extract Bank at Korea
      Research Institute of Bioscience and Biotechnology. The rumen fluid was collected
      before morning feeding from a fistulated Holstein cow fed timothy and commercial
      concentrate (TDN; 73.5%, crude protein; 19%, crude fat; 3%, crude fiber; 12%,
      crude ash; 10%, Ca; 0.8%, P; 1.2%) in the ratio of 3 to 2. The 30 ml of mixture,
      comprising McDougall buffer and rumen liquor in the ratio of 4 to 1, was
      dispensed anaerobically into serum bottles containing 0.3 g of timothy substrate
      and plant extracts (1% of total volume, respectively) filled with O2-free N2 gas
      and capped with a rubber stopper. The serum bottles were held in a shaking
      incubator at 39 degrees C for 24 h. Total gas production in all plant extracts
      was higher (p<0.05) than that of the control, and total gas production of ginger
      extract was highest (p<0.05). The methane emission was highest (p<0.05) at
      control, but lowest (p<0.05) at garlic extract which was reduced to about 20% of
      methane emission (40.2 vs 32.5 ml/g DM). Other plant extracts also resulted in a
      decrease in methane emissions (wormwood; 8%, onion; 16%, ginger; 16.7%, mandarin
      orange; 12%, honeysuckle; 12.2%). Total VFAs concentration and pH were not
      influenced by the addition of plant extracts. Acetate to propionate ratios from
      garlic and ginger extracts addition samples were lower (p<0.05, 3.36 and 3.38 vs
      3.53) than that of the control. Real-time PCR indicted that the ciliate
      associated methanogen population in all added plant extracts decreased more than
      that of the control, while the fibrolytic bacteria population increased. In
      particular, the F. succinogens community in added wormwood, garlic, mandarin
      orange and honeysuckle extracts increased more than that of the others. The
      addition of onion extract increased R. albus diversity, while other extracts did
      not influence the R. albus community. The R. flavefaciens population in added
      wormwood and garlic extracts decreased, while other extracts increased its
      abundance compared to the control. In conclusion, the results indicated that the
      plant extracts used in the experiment could be promising feed additives to
      decrease methane gas emission from ruminant animals while improving ruminal
      fermentation. 

PMID- 25049631
TI  - Effect of Sodium Nitrate and Nitrate Reducing Bacteria on In vitro Methane
      Production and Fermentation with Buffalo Rumen Liquor.
AB  - Nitrate can serve as a terminal electron acceptor in place of carbon dioxide and
      inhibit methane emission in the rumen and nitrate reducing bacteria might help
      enhance the reduction of nitrate/nitrite, which depends on the type of feed
      offered to animals. In this study the effects of three levels of sodium nitrate
      (0, 5, 10 mM) on fermentation of three diets varying in their wheat straw to
      concentrate ratio (700:300, low concentrate, LC; 500:500, medium concentrate, MC
      and 300:700, high concentrate, HC diet) were investigated in vitro using buffalo
      rumen liquor as inoculum. Nitrate reducing bacteria, isolated from the rumen of
      buffalo were tested as a probiotic to study if it could help in enhancing methane
      inhibition in vitro. Inclusion of sodium nitrate at 5 or 10 mM reduced (p<0.01)
      methane production (9.56, 7.93 vs. 21.76 ml/g DM; 12.20, 10.42 vs. 25.76 ml/g DM;
      15.49, 12.33 vs. 26.86 ml/g DM) in LC, MC and HC diets, respectively. Inclusion
      of nitrate at both 5 and 10 mM also reduced (p<0.01) gas production in all the
      diets, but in vitro true digestibility (IVTD) of feed reduced (p<0.05) only in LC
      and MC diets. In the medium at 10 mM sodium nitrate level, there was 0.76 to 1.18
      mM of residual nitrate and nitrite (p<0.01) also accumulated. In an attempt to
      eliminate residual nitrate and nitrite in the medium, the nitrate reducing
      bacteria were isolated from buffalo adapted to nitrate feeding and introduced
      individually (3 ml containing 1.2 to 2.3*10(6) cfu/ml) into in vitro incubations
      containing the MC diet with 10 mM sodium nitrate. Addition of live culture of
      NRBB 57 resulted in complete removal of nitrate and nitrite from the medium with
      a further reduction in methane and no effect on IVTD compared to the control
      treatments containing nitrate with autoclaved cultures or nitrate without any
      culture. The data revealed that nitrate reducing bacteria can be used as
      probiotic to prevent the accumulation of nitrite when sodium nitrate is used to
      reduce in vitro methane emissions. 

PMID- 25049632
TI  - Transgenic Expression of MsHsp23 Confers Enhanced Tolerance to Abiotic Stresses
      in Tall Fescue.
AB  - Tall fescue (Festuca arundinacea Schreb.) is an important cool season forage
      plant that is not well suited to extreme heat, salts, or heavy metals. To develop
      transgenic tall fescue plants with enhanced tolerance to abiotic stress, we
      introduced an alfalfa Hsp23 gene expression vector construct through
      Agrobacterium-mediated transformation. Integration and expression of the
      transgene were confirmed by polymerase chain reaction, northern blot, and western
      blot analyses. Under normal growth conditions, there was no significant
      difference in the growth of the transgenic plants and the non-transgenic
      controls. However, when exposed to various stresses such as salt or arsenic,
      transgenic plants showed a significantly lower accumulation of hydrogen peroxide
      and thiobarbituric acid reactive substances than control plants. The reduced
      accumulation of thiobarbituric acid reactive substances indicates that the
      transgenic plants possessed a more efficient reactive oxygen species-scavenging
      system. We speculate that the high levels of MsHsp23 proteins in the transgenic
      plants protect leaves from oxidative damage through chaperon and antioxidant
      activities. These results suggest that MsHsp23 confers abiotic stress tolerance
      in transgenic tall fescue and may be useful in developing stress tolerance in
      other crops. 

PMID- 25049633
TI  - Effect of cattle breed on meat quality, muscle fiber characteristics, lipid
      oxidation and Fatty acids in china.
AB  - The objective was to compare meat quality, muscle fiber characteristics, lipid
      oxidation and fatty acids of Limousin (LIM), Simmtental (SIM), Luxi (LX),
      Qinchuan (QC) and Jinnan (JN) offered the same diet in China. After finishing,
      eight bulls from each breed were randomly selected for slaughter at 18.5 months
      old. Longissimus dorsi (ld) muscle was taken from the carcass for meat quality
      evaluations. Breed had little effect on most of meat and fat color parameters
      except for Hue and b* in which QC had lower values. LIM showed higher pH (24 h)
      and better water holding capacity than other breeds. LIM showed the lowest dry
      matter content but the highest crude protein. LX and LIM had higher percentage
      and density of red muscle fiber than other breeds. Lipid oxidations were
      significantly lower in LIM than in QC, with the LX, SIM and JN having the
      intermediate values. Compared to other four breeds, QC provided the highest
      values of polyunsaturated fatty acids (PUFA), n-6 fatty acids and n-3 fatty
      acids. In conclusion, LIM scored better on most of meat quality characteristics;
      however, local breeds such as LX and QC also had better muscle fiber
      characteristics and better fatty acids composition. 

PMID- 25049634
TI  - Effects of catechins and wheat bran on the beef color in the late fattening
      period of hanwoo steers.
AB  - This study was conducted to evaluate the effects of dietary supplementation of
      catechins and wheat bran on growth performance, carcass characteristics and meat
      color using forty-eight Hanwoo steers. Each steer was randomly assigned to one of
      four treatments. Treatments were as follows: control, catechins, wheat bran, and
      catechins+wheat bran (CW). At the end of the feeding trial, blood samples were
      collected for analysis of hemoglobin and iron concentration, and then steers were
      slaughtered at a commercial abattoir. Catechins, wheat bran, and CW had no effect
      on growth performance and carcass characteristics. Percentage of myoglobin in M.
      longissimus dorsi was not affected by treatments. Percentage of oxymyoglobin was
      increased (p<0.05) by CW and maintained at the highest level (p<0.05) for CW
      during meat display time up to 24 h. Percentage of metmyoglobin was the lowest
      (p<0.05) for CW between 5 and 24 h during display time. Although blood iron
      concentration was not affected by treatments, total concentration of muscle iron
      was the lowest (p<0.05) for CW compared with that of other treatments. Therefore,
      the results of the present study suggest that CW may provide good protection
      against oxidation of myoglobin, and might be an effective dietary supplement for
      improving meat color in the late fattening period of Hanwoo steers. 

PMID- 25049635
TI  - Impacts of Limestone Multi-particle Size on Production Performance, Egg Shell
      Quality, and Egg Quality in Laying Hens.
AB  - This experiment was conducted to evaluate the effects of single or multi-particle
      size limestone on the egg shell quality, egg production, egg quality and feed
      intake in laying hens. A total of 280 laying hens (ISA brown) were used in this
      10-wk trial. Laying hens were randomly assigned to 4 treatments with 14
      replications per treatment and 5 adjacent cages as a replication (hens were caged
      individually). The experimental treatments were: i) L, basal diet+10% large
      particle limestone; ii) LS1, basal diet+8% large particle limestone+2% small
      particle limestone; iii) LS2, basal diet+6% large particle limestone+4% small
      particle limestone; iv) S, basal diet+10% small particle limestone. The egg
      production was unaffected by dietary treatments. The egg weight in S treatment
      was lighter than other treatments (p<0.05). The egg specific gravity in S
      treatment was lower than other treatments (p<0.05). The eggshell strength and
      eggshell thickness in S treatment were decreased when compared with other dietary
      treatments (p<0.05). The laying hens in LS1 and LS2 treatment had a higher
      average feed intake than the other two treatments (p<0.05). Collectively, the
      dietary multi-particle size limestone supplementation could be as efficient as
      large particle size limestone. 

PMID- 25049636
TI  - Effect of Arachidonic Acid-enriched Oil Diet Supplementation on the Taste of
      Broiler Meat.
AB  - To elucidate the relationship between the arachidonic acid (AA) content and the
      taste of broiler meat, the effects of AA-enriched oil (AAO) supplements on the
      fatty acid content and sensory perceptions of thigh meat were evaluated. Four
      types of oil, including corn oil (CO), a 1:1 mixture of AAO and palm oil (PO)
      (1/2 AAO), a 1:3 mixture of AAO and PO (1/4 AAO), and a 1:7 mixture of AAO and PO
      (1/8 AAO) were prepared. Each type of oil was mixed with silicate at a ratio of
      7:3, and added to the diet at a final proportion of 5% of fresh matter. Broiler
      chickens were fed these diets for 1 wk before slaughter. In thigh meat, the AA
      content of the 1/2 and 1/4 AAO groups was significantly higher than that of the
      CO group. The AA content in thigh meat (y, mg/g) increased linearly with
      increasing dietary AAO content (x, g/100 g of diet), according to the equation y
      = 0.5674+0.4596* (r(2) = 0.8454). The content of other fatty acids was not
      significantly different among the 4 diet groups. Sensory evaluation showed that
      the flavor intensity, umami (L-glutamate taste), kokumi (continuity,
      mouthfulness, and thickness), and aftertaste of the 1/2 and 1/4 AAO groups were
      significantly higher than that of the CO group. There were significant positive
      correlations between AA content in thigh meat and the flavor intensity, total
      taste intensity, umami, and aftertaste. These data suggest that the taste of
      broiler meat can be improved by the amount of dietary AA supplementation. 

PMID- 25049637
TI  - Partial Characterization of alpha-Galactosidic Activity from the Antarctic
      Bacterial Isolate, Paenibacillus sp. LX-20 as a Potential Feed Enzyme Source.
AB  - An Antarctic bacterial isolate displaying extracellular alpha-galactosidic
      activity was named Paenibacillus sp. LX-20 based on 16S rRNA gene sequence
      analysis. Optimal activity for the LX-20 alpha-galactosidase occurred at pH 6.0
      6.5 and 45 degrees C. The enzyme immobilized on the smart polymer Eudragit L-100
      retained 70% of its original activity after incubation for 30 min at 50 degrees
      C, while the free enzyme retained 58% of activity. The enzyme had relatively high
      specificity for alpha-D-galactosides such as p-nitrophenyl-alpha
      galactopyranoside, melibiose, raffinose and stachyose, and was resistant to some
      proteases such as trypsin, pancreatin and pronase. Enzyme activity was almost
      completely inhibited by Ag(+), Hg(2+), Cu(2+), and sodium dodecyl sulfate, but
      activity was not affected by beta-mercaptoethanol or EDTA. LX-20 alpha
      galactosidase may be potentially useful as an additive for soybean processing in
      the feed industry. 

PMID- 25049638
TI  - Chemical Characterization and Water Holding Capacity of Fibre-rich Feedstuffs
      Used for Pigs in Vietnam.
AB  - During two years, four samples per year were collected in Vietnam from rice bran,
      cassava residue, brewer's grain, tofu residue, soybean meal, coconut cake, sweet
      potato vines and water spinach for chemical analysis and assessment of water
      holding capacity (WHC). The selected feedstuffs represent fibre-rich plant
      sources and agro-industry co-products commonly used in pig feeding in Vietnam.
      The content (g/kg DM) of crude protein (CP), ether extract (EE) and non-starch
      polysaccharides (NSP) varied between feedstuffs and ranged from 21 to 506 for CP,
      from 14 to 118 for EE and from 197 to 572 for NSP. Cassava residue had a high
      starch content of 563 g/kg DM, while sweet potato vines, water spinach, coconut
      cake and soybean meal had a high content of sugars (63-71 g/kg DM). The content
      of individual neutral sugars varied between feed ingredients, with the highest
      content of arabinose, galactose and glucose in tofu residue, the highest content
      of xylose in brewer's grain and the highest content of mannose in coconut cake.
      The content of uronic acid was high for cassava residue, tofu residue, sweet
      potato vines and water spinach (57-88 g/kg DM). The content of soluble non
      cellulosic polysaccharides (S-NCP) was positively correlated (r(2) = 0.82) to the
      WHC. The content (g/kg DM) of CP, NDF, neutral sugars, total NSP, total NCP, S
      NCP and total dietary fibre in tofu residue, water spinach and coconut cake
      varied (p<0.05) between years. In conclusion, diet formulation to pigs can be
      improved if the variation in chemical composition of the fibre fraction and in
      WHC between potential feed ingredients is taken into account. 

PMID- 25049639
TI  - Effects of Dietary Lipid Source and Level on Growth Performance, Blood Parameters
      and Flesh Quality of Sub-adult Olive Flounder (Paralichthys olivaceus).
AB  - This study was conducted to investigate the effects of dietary lipid source and
      level on growth performance, blood parameters, fatty acid composition and flesh
      quality of sub-adult olive flounder Paralichthys olivaceus. Eight experimental
      diets were formulated to contain 5% squid liver oil (SLO), 5% linseed oil (LO),
      5% soybean oil (SO), a mixture of 1% squid liver oil, 2% linseed oil and 2%
      soybean oil (MIX), no lipid supplementation with high protein level (LL-HP), 10%
      squid liver oil (HL-SLO), a mixture of 1% squid liver oil, 4.5% linseed oil and
      4.5% soybean oil (HL-VO), and 1% squid liver oil with high starch level (LL-HC),
      respectively. Two replicate groups of fish (average initial weight of 296 g) were
      fed the diets for 17 wks. After 5 wks, 11 wks and the end of the feeding trial,
      five fish from each tank were randomly sampled for analysis of body composition.
      At the end of the feeding trial, final mean weight of fish fed the LL-HP diet was
      significantly (p<0.05) higher than that of fish fed the HL-VO diet, but did not
      differ significantly from those of fish fed the SLO, LO, SO, MIX, HL-SLO and LL
      HC diets. Fish fed the LL-HP diet showed significantly higher feed efficiency
      than fish fed the LO, HL-SLO and HL-VO diets. Feed efficiency of fish fed the LO,
      SO and MIX diets were similar to those of fish fed the SLO and HL-SLO diets. Fish
      fed the HL-SLO diet showed significantly higher total cholesterol content in
      plasma compared with other diets. Fatty acid composition of tissues was reflected
      by dietary fatty acid composition. The highest linoleic (LA) and linolenic acid
      (LNA) contents in the dorsal muscle were observed in fish fed the SO and LO
      diets, respectively, regardless of feeding period. The highest eicosapentaenoic
      acid (EPA) content in the dorsal muscle was observed in fish fed the LL-HP and LL
      HC diets after 11 and 17 weeks of feeding, respectively. Fish fed the SLO and HL
      SLO diets showed higher docosahexaenoic acid (DHA) content than that of other
      treatments after 11 and 17 weeks of feeding, respectively. Dietary inclusion of
      vegetable oils reduced n-3 HUFA contents in the dorsal muscle and liver of fish.
      The n-3 HUFA contents in tissues of fish fed the SLO and HL-SLO diets were higher
      than those of fish fed other diets, except for the LL-HP and LL-HC diets.
      Hardness, gel strength, chewiness and cohesiveness values of dorsal muscle in
      fish were significantly affected by dietary lipid source. The results of this
      study indicate that fish oil in fish meal based diets for sub-adult olive
      flounder could be replaced by soybean oil and linseed oil without negative
      effects on growth and feed utilization. 

PMID- 25049640
TI  - Dietary carob pods on growth performance and meat quality of fattening pigs.
AB  - In this experiment the effect of dietary carob pods in the growth performance of
      fattening pigs and their meat quality, including steak chemical composition and
      fatty acid profile, were examined. A total of 160 weaning piglets, 30 days old,
      were allocated into four equal groups with 4 subgroups of 5 female and 5 males
      each. The animals were fed with isocaloric and isonitrogenous diets, containing
      either 0 or 75 or 100 or 125 g of carob pods per kg of feed. At the end of the
      experiment, on the 180 day of age, carcass subcutaneous fat thickness, steak
      chemical composition and steak fatty acid profile were determined. The results of
      the experiment showed that the dietary addition of 75 or 100 g/kg carob pods
      increased body weight at slaughter and carcass weight. No significant effect was
      noticed on the other examined carcass parameters. Consequently, carob pods could
      be suggested as a potential feed for fattening pigs without any adverse effect on
      their meat quality. 

PMID- 25049641
TI  - Effects of outdoor housing of piglets on behavior, stress reaction and meat
      characteristics.
AB  - Well-designed housing systems are important from the viewpoint of animal welfare
      and improvement of meat production. In this study, we investigated the effects of
      outdoor housing of pigs on their behavior, cortisol levels, and meat
      characteristics. Two groups that were born and raised in a spacious outdoor pen
      (4*10 m for every two sows) or a minimum-sized standard pen in a piggery (1.9*2.2
      m for every sow) were studied. When their behaviors at the age of 2 to 3 wk were
      observed, the number of rooting episodes tended to be larger (p = 0.0509) and the
      total time of rooting tended to be longer (p = 0.0640) in the outdoor-housed
      piglets although the difference was not significant. Basal salivary cortisol
      levels of the outdoor piglets at the age of 4 wk were significantly lower than
      those of the indoor piglets (5.0+/-0.59 ng/ml vs. 11.6+/-0.91 ng/ml, 30 min after
      treatment), although their plasma cortisol levels were similar (53.3+/-3.54 ng/ml
      vs. 59.9+/-4.84 ng/ml, 30 min after treatment). When the ears were pierced at
      weaning, plasma and salivary cortisol levels were increased in both groups, even
      at 15 min after piercing. However, the increase in the outdoor-housed group was
      significantly less than that in the indoor-housed group. Throughout their lives,
      body weight and daily gain of the pigs were not significantly different between
      the two groups. In a meat taste preference test taken by 20 panelists, saltiness,
      flavor, and color of the outdoor-housed pork were found to be more acceptable.
      Moreover, when an electronic taste-sensing device was utilized, the C00 and CPA
      C00 outputs (3.78+/-0.07 and -0.20+/-0.023), which correspond to compounds of
      bitterness and smells, respectively, were significantly lower in the outdoor
      housed pork (5.03+/-0.16 and -0.13+/-0.009). Our results demonstrate that the
      outdoor housing system for piglets induces natural behaviors such as rooting and
      suppresses the strongest stress reaction of piglets, which could be important for
      animal welfare. Moreover, the outdoor housing system might change muscle
      characteristics and improve pork bitterness, flavor, and color. These changes may
      be preferred by consumers, increasing the sale of these meats. 

PMID- 25049642
TI  - Differential Proteome Analysis of Breast and Thigh Muscles between Korean Native
      Chickens and Commercial Broilers.
AB  - The Korean native chickens (WoorimotdakTM, KNC) and commercial broilers (Ross,
      CB) show obvious differences in meat flavor after cooking. To understand the
      contribution of protein and peptide for meat flavor, 2-dimensional (2-D) gel
      electrophoresis and matrix-assisted laser desorption-ionization time-of-flight
      (MALDI-TOF) mass spectrometry was performed. A total of 16 protein spots were
      differentially expressed in the breast and thigh meat between the two breeds. A
      total of seven protein spots were represented by different levels between KNC and
      CB for breast meat. Among them three protein spots (TU39149, TU40162 and TU39598)
      showed increases in their expressions in KNC while other four protein spots
      (BU40125, BU40119, BU40029 and BU39904) showed increases in CB. All nine protein
      spots that were represented by different levels between KNC and CB for thigh meat
      showed increases in their expression in KNC. Phosphoglucomutase 1 (PGM 1), myosin
      heavy chain (MyHC), heat shock protein B1 (HSP27), cytochrome c reductase (Enzyme
      Q), Glyoxylase 1, DNA methyltransferase 3B (DNA MTase 3) were identified as the
      main protein spots by MALDI-TOF mass spectrometry. These results can provide
      valuable basic information for understanding the molecular mechanism responsible
      for breed specific differences in meat quality, especially the meat flavour. 

PMID- 25049643
TI  - Expression Profiles of the Insulin-like Growth Factor System Components in Liver
      Tissue during Embryonic and Postnatal Growth of Erhualian and Yorkshire
      Reciprocal Cross F1 Pigs.
AB  - In Erhualian and Yorkshire reciprocal cross F1 pig populations, we examined the
      mRNA expression characteristic of liver-derived IGF-1, IGF-1R, IGF-2, IGF-2R and
      IGFBP-3 during the embryonic and postnatal developmental periods (E50, E70, E90,
      D1, D20, D70, D120 and D180). Our results demonstrated that the IGF-system genes
      mRNA levels exhibited an ontogenetic expression pattern, which was potentially
      associated with the porcine embryonic development, postnatal growth,
      organogenesis and even the initiation and acceleration of puberty. The expression
      pattern of IGF-system genes showed variation in the reciprocal cross (F1 YE and
      EY pigs). This study also involved the expression features of imprinted genes IGF
      2 and IGF-2R. The parent-of-origin effect of imprinted genes was reflected by
      their differential expression between the reciprocal crosses populations. The
      correlation analysis also indicated that the regulatory network and mechanisms
      involved in the IGF system were a complex issue that needs to be more fully
      explored. A better understanding of IGF system components and their interactive
      mechanisms will enable researchers to gain insights not only into animal
      organogenesis but also into somatic growth development and even reproduction. 

PMID- 25049644
TI  - Identification of the SNP (Single Nucleotide Polymorphism) for Fatty Acid
      Composition Associated with Beef Flavor-related FABP4 (Fatty Acid Binding Protein
      4) in Korean Cattle.
AB  - In this study, we investigated the relationship between unsaturated fatty acids
      influencing beef flavor and four types of SNPs (c.280A>G, c.388G>A, c.408G>C and
      c.456A>G) located at exon 2, 3 and 4 of the FABP4 gene, which is a fatty acid
      binding protein 4 in Korean cattle (n = 513). When analyzing the relationship
      between single genotype, fatty acids and carcass trait, individuals of GG, GG, CC
      and GG genotypes that are homozygotes, had a higher content of unsaturated fatty
      acids and marbling scores than other genotypes (p<0.05). Then, haplotype block
      showed strong significant relationships not only with unsaturated fatty acids
      (54.73%), but also with marbling scores (5.82) in ht1*ht1 group (p<0.05). This
      ht1*ht1 group showed significant differences with unsaturated fatty acids and
      marbling scores that affected beef flavor in Korean cattle. Therefore, it can be
      inferred that the ht1*ht1 types might be valuable new markers for use in the
      improvement of Korean cattle. 

PMID- 25049645
TI  - Genetic Diversity of mtDNA D-loop and Maternal Origin of Three Chinese Native
      Horse Breeds.
AB  - In order to protect the genetic resource of native horse breeds, the genetic
      diversity of mitochondrial DNA (mtDNA) D-loop of three native horse breeds in
      western China were investigated. Forty-three 600 bp mtDNA D-loop sequences were
      analyzed by PCR and sequencing techniques, 33 unique haplotypes with 70
      polymorphic sites were detected in these horses, which account for 11.67% of 600
      bp sequence analyzed, showing the abundant genetic diversity of the three native
      horse breeds in western China. The Neighbour-Joining (NJ) phylogenetic tree based
      on 247 bp of 43 D-loop sequences demonstrated the presence of seven major
      lineages (A to G), indicating that the three native horse breeds in western China
      originated from multiple maternal origins. Consistent with the front, the NJ
      phylogenetic tree based on 600 bp of mtDNA D-loop sequences of 43 Chinese western
      native horses and 81 sequences of six horse breeds from GenBank indicated that
      the three horse breeds had distributed into the seven major lineages (A to G).
      The structure of the phylogenic tree is often blurred because the variation in a
      short segment of the mitochondrial genome is often accompanied by high levels of
      recurrent mutations. Consequently, longer D-loop sequences are helpful in
      achieving a higher level of molecular resolution in horses. 

PMID- 25049646
TI  - Genetic diversity of myanmar and indonesia native chickens together with two
      jungle fowl species by using 102 indels polymorphisms.
AB  - The efficiency of insertion and/or deletion (indels) polymorphisms as genetic
      markers was evaluated by genotyping 102 indels loci in native chicken populations
      from Myanmar and Indonesia as well as Red jungle fowls and Green jungle fowls
      from Java Island. Out of the 102 indel markers, 97 were polymorphic. The average
      observed and expected heterozygosities were 0.206 to 0.268 and 0.229 to 0.284 in
      native chicken populations and 0.003 to 0.101 and 0.012 to 0.078 in jungle fowl
      populations. The coefficients of genetic differentiation (Gst) of the native
      chicken populations from Myanmar and Indonesia were 0.041 and 0.098 respectively.
      The genetic variability is higher among native chicken populations than jungle
      fowl populations. The high Gst value was found between native chicken populations
      and jungle fowl populations. Neighbor-joining tree using genetic distance
      revealed that the native chickens from two countries were genetically close to
      each other and remote from Red and Green jungle fowls of Java Island. 

PMID- 25049647
TI  - Phylogeography and Population Genetic Structure of Amur Grayling Thymallus grubii
      in the Amur Basin.
AB  - Amur grayling, Thymallus grubii, is an important economic cold freshwater fish
      originally found in the Amur basin. Currently, suffering from loss of habitat and
      shrinking population size, T. grubii is restricted to the mountain river branches
      of the Amur basin. In order to assess the genetic diversity, population genetic
      structure and infer the evolutionary history within the species, we analysised
      the whole mitochondrial DNA control region (CR) of 95 individuals from 10 rivers
      in China, as well as 12 individuals from Ingoda/Onon and Bureya River throughout
      its distribution area. A total of 64 variable sites were observed and 45
      haplotypes were identified excluding sites with gaps/missing data. Phylogenetic
      analysis was able to confidently predict two subclade topologies well supported
      by maximum-parsimony and Bayesian methods. However, basal branching patterns
      cannot be unambiguously estimated. Haplotypes from the mitochondrial clades
      displayed local homogeneity, implying a strong population structure within T.
      grubii. Analysis of molecular variance detected significant differences among the
      different geographical rivers, suggesting that T. grubii in each river should be
      managed and conserved separately. 

PMID- 25049648
TI  - The Effect of Yerba Mate (Ilex paraguarensis) Supplementation on the Productive
      Performance of Dorper Ewes and Their Progeny.
AB  - Yerba Mate (Ilex paraguariensis), a tea known for its high antioxidant content,
      was supplemented to 30 of 60 ewes for 13 wks to assess its effect on their
      productive performance. A 2.5% inclusion rate of Yerba Mate (YM) in a pelleted
      concentrate diet decreased feed intake and live weight (LW) during the first few
      weeks post partum (p<0.001). Overall, the YM group ate less (2,092+/-78 g/d)
      pellet than the control (CTRL) one (2,434+/-83 g/d); similarly, LW was lower in
      the YM group compared to the CTRL one, 64.9+/-1.6 kg and 67.3+/-1.4 kg,
      respectively. Lambs' birth weight and growth rates were not affected. At birth,
      lambs' LW were similar between the Yerba Mate and control groups (4.2+/-0.5 kg
      and 4.1+/-0.4 kg, respectively. At the end of the trial, Yerba Mate lambs weighed
      15.7+/-0.4 kg while CTRL lambs weighed 16.1+/-0.4 kg. Average daily growth rate
      was similar between the two groups and ranged from 176+/-19 to 234 +/-24 g/d. The
      inclusion of Yerba Mate in a pelleted diet increased milk fat, protein and total
      solids content while it decreased milk lactose content. Further work is required
      to investigate the mechanisms by which Yerba Mate supplementation affects feed
      intake and milk composition. 

PMID- 25049649
TI  - In vitro-growth and Gene Expression of Porcine Preantral Follicles Retrieved by
      Different Protocols.
AB  - This study was conducted to determine how the isolation method of the porcine
      preantral follicles influenced the following follicular growth in vitro.
      Mechanical and enzymatical isolations were used for retrieving the follicles from
      prepubertal porcine ovaries, and in vitro-growth of the follicles and the
      expression of folliculogenesis-related genes were subsequently monitored. The
      enzymatic retrieval with collagenase treatment returned more follicles than the
      mechanical retrieval, while the percentage of morphologically normal follicles
      was higher with mechanical retrieval than with enzymatic retrieval. After 4 days
      of culture, mechanically retrieved, preantral follicles yielded more follicles
      with normal morphology than enzymatically retrieved follicles, which resulted in
      improved follicular growth. The mRNA expression of FSHR, LHR Cx43, DNMT1 and
      FGFR2 genes was significantly higher after culture of the follicles retrieved
      mechanically. These results suggest that mechanical isolation is a better method
      of isolating porcine preantral follicles that will develop into competent oocytes
      in in vitro culture. 

PMID- 25049650
TI  - Feed intake, digestibility, and N retention in cattle fed rice straw and para
      grass combined with different levels of protein derived from cassava foliage.
AB  - Eight male cattle of Local Yellow breed with an average live weight of 121 kg and
      an average age of 18 months were used to evaluate the effects of different levels
      of sun-dried cassava foliage supplementation (Manihot esculenta) on intake,
      digestibility and N retention. Rice straw ad libitum and para grass (Brachiaria
      mutica) at 1% DM of BW comprised the basal diet. The study was arranged as a 4*4
      double Latin square design, with cassava foliage contributing 0, 0.8, 1.6 or 2.4
      g CP/kg BW. The cattle selected cassava leaves in preference to petioles. Petiole
      intake decreased from 64 to 48% of offered petioles when the cassava foliage
      proportion increased from the lowest to the highest level. The cattle consumed
      all the leaves at the two lower levels of cassava foliage inclusion and 91% at
      the highest level. Rice straw intake decreased significantly as the level of
      cassava foliage increased. Intake of DM, OM, NDF, and ADF increased significantly
      with increasing intake of cassava foliage. Daily DM intake per 100 kg BW
      increased from 2.7 to 3.2 kg with increasing cassava foliage intake. No effect on
      CP digestibility was detected when the level of cassava foliage increased.
      Digestibility of DM, OM, NDF and ADF was significantly higher in the group fed no
      cassava foliage than in the other groups. N retention increased from 16 to 28 g/d
      with the first level of cassava foliage inclusion, but levelled out at the two
      highest levels. N excretion increased in both faeces and urine as a response to
      higher intake of cassava foliage. Maximum N retention occurred when 40% of total
      N intake came from cassava foliage (equivalent to 1.3 g CP/kg BW). 

PMID- 25049651
TI  - Effects of ruminal infusion of garlic oil on fermentation dynamics, Fatty Acid
      profile and abundance of bacteria involved in biohydrogenation in rumen of goats.
AB  - This study aimed to investigate the effects of ruminal infusion of garlic oil
      (GO) on fermentation dynamics, fatty acid (FA) profile, and abundance of bacteria
      involved in biohydrogenation in the rumen. Six wethers fitted with ruminal
      fistula were assigned to two groups for cross-over design with a 14-d interval.
      Each 30-d experimental period consisted of a 27-d adaptation and a 3-d sample
      collection. Goats were fed a basal diet without (control) or with GO ruminal
      infusion (0.8 g/d). Ruminal contents collected before (0 h) and at 2, 4, 6, 8,
      and 10 h after morning feeding were used for fermentation analysis, and 0 h
      samples were further used for FA determination and DNA extraction. Garlic oil had
      no influence on dry matter intakes of concentrate and hay. During ruminal
      fermentation, GO had no effects on total VFA concentration and individual VFA
      molar proportions, whereas GO increased the concentrations of ammonia nitrogen
      and microbial crude protein (p<0.05). Compared with control, GO group took a
      longer time for total VFA concentration and propionate molar proportion to reach
      their respective maxima after morning feeding. The ratio of acetate to propionate
      in control reduced sharply after morning feeding, whereas it remained relatively
      stable in GO group. Fatty acid analysis showed that GO reduced saturated FA
      proportion (p<0.05), while increasing the proportions of C18, t11-18:1 (TVA),
      c9,t11-conjugated linoleic acid (c9,t11-CLA), t10,c12-CLA, and polyunsaturated FA
      (p<0.05). The values of TVA/(c9,t11-CLA+TVA) and C18:0/(TVA+ C18:0) were reduced
      by GO (p<0.05). Real-time PCR showed that GO tended to reduce Butyrivibrio
      proteoclasticus abundance (p = 0.058), whereas GO had no effect on total
      abundance of the Butyrivibrio group bacteria. A low correlation was found between
      B. proteoclasticus abundance and C18:0/(TVA+C18:0) (p = 0.910). The changes of
      fermentation over time suggested a role of GO in delaying the fermentation
      process and maintaining a relatively modest change of ruminal environment. The
      inhibitory effects of GO on the final step of biohydrogenation may be related to
      its antibacterial activity against B. proteoclasticus and other unknown bacteria
      involved. 

PMID- 25049652
TI  - Effects of Protein Level and Mangosteen Peel Pellets (Mago-pel) in Concentrate
      Diets on Rumen Fermentation and Milk Production in Lactating Dairy Crossbreds.
AB  - Four, lactating dairy crossbreds (50%*50% Holstein Friesian*Native Zebu cattle)
      were randomly assigned according to a 2*2 factorial arrangement (two protein
      levels and two levels of mangosteen peel pellets (Mago-pel)) in a 4*4 Latin
      square design to receive four dietary treatments. All cows received concentrate
      at a proportion of 1 kg concentrate per 2 kg of milk yield, and urea-treated 5%
      rice straw (UTRS) was given ad libitum. It was found that total dry matter
      intakes, nutrient digestibility, ruminal pH and NH3-N concentrations were not
      affected (p>0.05) by treatments. Concentrations of ruminal pH and NH3-N were not
      affected by dietary treatments although the concentration of BUN varied
      significantly (p<0.05) between protein levels (p<0.05). The populations of rumen
      bacteria and fungal zoospores did not differ among treatments (p>0.05); however,
      the population of protozoa was decreased (p<0.05) when cows received Mago-pel
      supplementation. The composition of the population of bacteria, identified by
      real-time PCR technique, including total bacteria, methanogens, Fibrobacter
      succinogenes and Ruminococcus albus was similar (p>0.05) among dietary treatments
      (p>0.05); however, copy numbers of Ruminococcus flavefaciens was increased when
      protein level increased (p<0.05). Microbial protein synthesis, in terms of both
      quantity and efficiency, was enriched by Mago-pel supplementation. Milk yield was
      greatest in cows fed UTRS based diets with concentrate containing protein at 16%
      CP with Mago-pel, but were lowest without Mago-pel (p<0.05). In addition, protein
      level and supplementation of Mago-pel did not affect (p>0.05) milk composition
      except solids-not-fat which was higher in cows fed the diet with 19% CP.
      Therefore, feeding a concentrate containing 16% CP together with 300 g/hd/d Mago
      pel supplementation results in changes in rumen fermentation and microbial
      population and improvements in milk production in lactating dairy crossbreds fed
      on UTRS. 

PMID- 25049653
TI  - Effects of processing of starter diets on performance, nutrient digestibility,
      rumen biochemical parameters and body measurements of brown swiss dairy calves.
AB  - In order to investigate the effect of physical forms of starter diets on
      performance, weaning age, nutrient digestibility and rumen biochemical factors,
      24 female of neonatal Brown Swiss calves (average body weight of 39.5+/-1.2 kg)
      were randomly assigned to three treatments. Dietary treatments were mashed (MS),
      pelleted (PS), and texturized (TS) starter using 8 calves from birth till 90 days
      of age in each treatment. Diets were formulated to be iso-nitrogenous with 21%
      crude protein. Based on the experimental results, calves that received PS and TS
      diets, had significant higher average daily gain (ADG) than those receiving MS
      (p<0.01). Dry matter intake in calves fed PS and TS was greater than calves fed
      MS (p<0.05), but there was no significant difference in feed efficiency.
      Treatments had no effect on initiation of rumination. Weaning age of calves in MS
      was longer than the other two treatments (p<0.05). Crude protein and organic
      matter digestibility in MS treated calves were lower than other treatments
      (p<0.05). No differences were observed in neutral detergent fiber (NDF) and ash
      digestibility among treatments (p>0.05). Ruminal pH was higher (p<0.01) in MS
      than the other groups, but ruminal ammonia (g/dl) concentration was not different
      among the treatments. Body measurements such as body length, pin width, hip
      width, pin to hip length, size of metacarpus and metatarsus bones, hip height,
      wither height, stomach size and heart girth were not significantly different
      among the treatments. Overall, it is concluded that starter diets in the form of
      pellet and texture can improve performance in neonatal Brown Swiss calves
      compared to the mashed form. 

PMID- 25049654
TI  - The effect of level of wheat inclusion in diets for growing and finishing pigs on
      performance, nutrient digestibility and gastric ulceration.
AB  - Four experimental diets were formulated to contain 700 g/kg cereal with
      decreasing levels of wheat:barley inclusion. Diet 1 contained 700 g/kg wheat,
      diet 2 contained 600 g/kg wheat and 100 g/kg barley, diet 3 contained 500 g/kg
      wheat and 200 g/kg barley and diet 4 contained 400 g/kg wheat and 300 g/kg
      barley. The diets were offered to pigs on three trials to investigate effects on
      the performance of individually (n = 72) and group housed (n = 480) pigs and on
      nutrient digestibility in pigs housed in metabolizm crates (n = 24). Performance
      was assessed from 10 wks of age until slaughter and carcass characteristics were
      measured. For the group performance study, one pig from each pen (in total 24) at
      10, 15 wks and at finish were slaughtered to ascertain scores for stomach
      ulceration, stomach weights and intestinal length. Level of wheat inclusion did
      not significantly (p>0.05) affect liveweight gain (LWG) or feed conversion ratio
      (FCR). Feed intake was lowest (p<0.05) for individually housed pigs offered diets
      containing 700 g/kg wheat during the 10-15 wk period, which indicated that
      individually housed pigs attempted to eat to a constant energy intake. There was
      little evidence of stomach ulceration across treatments and increasing wheat
      inclusion had no detrimental effect. Higher levels of wheat inclusion tended to
      increase backfat depth at the P2 position which could lead to increasing grading
      penalties in a commercial situation although more research is required in this
      area. Increasing level of wheat inclusion increased digestible energy (DE)
      content but the lack of effect on FCR and killing out percentage indicated that
      utilization of energy from barley and wheat was similar. Digestibility
      coefficients increased linearly with increasing wheat content, which can be
      attributed to the lower level of fibre and higher level of starch in wheat
      compared with barley. 

PMID- 25049655
TI  - Effect of age and caponization on blood parameters and bone development of male
      native chickens in taiwan.
AB  - An experiment was carried out to determine the effect of age and caponization on
      the development blood and bone characteristics development in male country
      chickens in Taiwan. A total of two hundred 8-wk-old LRI native chicken cockerels,
      Taishi meat No.13 from LRI-COA, were used as experimental animals. Cockerels were
      surgically caponized at 8 wks of age. Twelve birds in each group were bled and
      dressed from 8 wks to 35 wks of age at 1 to 5 wk intervals. The results indicated
      that the plasma testosterone concentration was significantly (p<0.05) lower in
      capons after 12 wks of age (caponized treatment after 4 wks) than that of the
      intact males. The relative tibia weight, bone breaking strength, cortical
      thickness, bone ash, bone calcium, bone phosphorus and bone magnesium contents
      were significantly (p<0.05) higher in intact males, while capons had higher
      (p<0.05) plasma ionized calcium, inorganic phosphorus and alkaline phosphatase
      concentration. The plasma testosterone concentration, relative tibia weight,
      tibia length, breaking strength, cortical thickness, bone ash, calcium, and
      phosphorus contents of intact males chickens increased significantly (p<0.05)
      with the advance of age. In addition, the relative tibia weight of capons peaked
      at 18 wks of age, and declined at 35 wks of age. The bone ash, calcium and
      phosphorus content increased most after 14 wks of age in male native chickens in
      Taiwan. Also, tibia length and cortical thickness peaked at 22 wks of age.
      However, the peak of bone strength was found at 26 wks of age. These findings
      support the assertion that androgens can directly influence bone composition
      fluxes in male chickens. Caponization caused a significant increase in bone loss
      at 4 wks post treatment, which reflected bone cell damage, and demonstrated
      reductions in the relative tibia weight, breaking strength, cortical thickness,
      bone ash, calcium, phosphorus and magnesium contents, and increases in plasma
      ionized calcium, inorganic phosphorus and alkaline phosphatase concentration. 

PMID- 25049656
TI  - Effect of Medium-chain Triglyceride (MCT) on Growth Performance, Nutrient
      Digestibility, Blood Characteristics in Weanling Pigs.
AB  - One hundred and twenty weanling pigs in experiment 1 (Exp. 1) (6.91+/-0.99 kg; 21
      d of age) and Exp. 2 (10.20+/-1.09 kg; 28 d of age) were used in two 42-d and 35
      d experiments to evaluate the effect of medium-chain-triglyceride (MCT) on growth
      performance, apparent total tract digestibility (ATTD) of nutrients and blood
      profile. In both of Exp. 1 and Exp. 2, the same dietary treatments were utilized
      as follows : i) negative control (NC), ii) positive control (PC), NC+antibiotics
      (40 mg/kg Tiamulin, 110 mg/kg Tylosin, and 10 mg/kg Enramycin, iii) MCT3,
      NC+0.32% (phase 1, 2 and 3) MCT, and iv) MCT5, NC+0.55% (phase 1), 0.32% (phase 2
      and 3) MCT. In Exp. 1, the pigs fed MCT5 diets had higher (p<0.05) ADG compared
      to NC treatment during the first 2 wk. From d 15 to 28, the ATTD of energy was
      improved (p<0.05) by MCT3 compared to the PC treatment. No effect has been
      observed on the blood profiles [red blood cell (RBC), white blood cell (WBC),
      immunoglobulin-G (IgG), lymphocyte concentration] measured in this study. In Exp.
      2, the ADG were increased (p<0.05) by the MCT5 treatment than the PC treatment
      from d 0 to 14. Pigs fed PC treatment diet had lower ADFI (p<0.05) and better FCR
      (p<0.05) than NC treatment, whereas no differences were shown between MCT
      treatments and NC or PC treatment from d 15 to 35 and overall phase. The ATTD of
      DM and nitrogen were improved (p<0.05) by the effect of MCT5 related to the NC
      and PC treatment at the end of 2nd and 5th wk. The pigs fed MCT3 had higher
      (p<0.05) energy digestibility than PC treatment. No effects were seen in the
      blood profiles we measured (WBC, RBC, lymphocyte and immunoglobulin-G). In
      conclusion, the addition of MCT in the weanling pigs diet can improve the ADG and
      digestibility during the earlier period (first 2 wks), but had little effect on
      the blood characteristics. 

PMID- 25049657
TI  - Effect of Dietary L-ascorbic Acid (L-AA) on Production Performance, Egg Quality
      Traits and Fertility in Japanese Quail (Coturnix japonica) at Low Ambient
      Temperature.
AB  - Environmental stress boosts the levels of stress hormones and accelerates energy
      expenditure which subsequently imbalance the body's homeostasis. L-ascorbic acid
      (L-AA) has been recognized to mitigate the negative impact of environmental
      stress on production performances in birds. The present investigation was carried
      out to elucidate the effect of different dietary levels of L-AA on production
      performance, egg quality traits and fertility in Japanese quail at low ambient
      temperature. Sixty matured females (15 wks) were equally divided into three
      groups (20/group) based on the different dietary levels of L-AA (0, 250 and 500
      ppm) and coupled with an equal number of males (1:1) obtained from the same
      hatch. They were managed in uniform husbandry conditions without restriction of
      feed and water at 14 h photo-schedule. Except for feed efficiency, body weight
      change, feed consumption and hen-day egg production were recorded highest in 500
      ppm L-AA supplemented groups. Among the all egg quality traits studied, only
      specific gravity, shell weight and thickness differed significantly (p<0.05) in
      the present study. Fertility was improved significantly (p<0.01) to a dose
      dependent manner of L-AA. The findings of the present study concluded that
      dietary L-AA can be a caring management practice at least in part to alleviate
      the adverse effect of cold induced stress on production performance in Japanese
      quail. 

PMID- 25049658
TI  - Effects of bacteriophage supplementation on egg performance, egg quality, excreta
      microflora, and moisture content in laying hens.
AB  - An experiment was conducted to evaluate the effects of bacteriophage
      supplementation on egg performance, egg quality, excreta microflora, and moisture
      content in laying hens. A total of 288 Hy-line brown commercial laying hens (36
      wk-old) were randomly allotted to 4 treatments in this 6-wk trial and dietary
      treatments included: i) CON, basal diet; ii) T1, CON+0.020% bacteriophage; iii)
      T2, CON+0.035% bacteriophage; iv) T3, CON+0.050% bacteriophage. There were 6
      replicates for each treatment with 6 adjacent cages (2 hens/cage). Laying hens in
      T2 and T3 treatments had higher (p<0.05) egg production than those in CON and T1
      treatments during wk 0 to 3. In addition, egg production in T1, T2, and T3
      treatments was increased (p<0.05) compared with that in CON treatment during wk 4
      to 6. At wk 4 and 5, birds in T2 group had higher (p<0.05) HU than those in CON.
      In addition, at wk 5 and 6, HU in birds fed T1 and T3 diets was greater (p<0.05)
      than those fed CON diet. E. coli and Salmonella spp. concentrations in excreta
      were decreased (p<0.05) by T1, T2, and T3 treatments. However, egg weight, egg
      shell color, yolk height, yolk color unit, egg shell strength, egg shell
      thickness, egg gravity, and excreta moisture content were not influenced by
      dietary treatments during the entire experimental period. In conclusion,
      bacteriophage supplementation has beneficial effects on egg production, egg
      albumen, and excreta microflora concentration in laying hens. 

PMID- 25049659
TI  - Differential Expression of Th1- and Th2- Type Cytokines in Peripheral Blood
      Mononuclear Cells of Murrah Buffalo (Bubalus Bubalis) on TLR2 Induction by B.
      Subtilis Peptidoglycan.
AB  - Peripheral blood mononuclear cells (PBMCs) discriminate microbial pathogens and
      induce T-cell responses of appropriate effector phenotype accordingly. Toll-like
      receptors (TLRs), in part, mediate this microbial recognition and differentiation
      while the development of T-cell effector functions critically depends on the
      release of Th1- or Th2- type cytokines. In the present study, buffalo PBMCs were
      stimulated under in vitro culture conditions by Bacillus subtilis cell wall
      petidoglycan, a TLR2 ligand, in a dose-and time- dependent manner. The expression
      of TLR2 as well as the subsequent differential induction of the Th1 and Th2 type
      cytokines was measured. Stimulation was analyzed across five doses of
      peptidoglycan (10 MU/ml, 20 MUg/ml, 30 MUg/ml, 40 MUg/ml and 50 MUg/ml) for 3 h,
      12 h, 24 h and 36 h incubation periods. We observed the induction of TLR2
      expression in a dose- and time-dependent manner and the peptidoglycan induced
      tolerance beyond 30 MUg/ml dose at all incubation periods. The correlation
      between peptidoglycan stimulation and TLR2 induction was found positive at all
      doses and for all incubation periods. Increased production of all the cytokines
      was observed at low doses for 3 h incubation, but the expression of IL-4 was
      relatively higher than IL-12 at the higher antigen doses, indicating tailoring
      towards Th2 response. At 12 h incubation, there was a pronounced decrease in IL-4
      and IL-10 expression relative to IL-12 in a dose- dependent manner, indicating
      skewing to Th1 polarization. The expression of IL-12 was highest for all doses
      across all the incubation intervals at 24 h incubation, indicating Th1
      polarization. The relative expression of TNF-alpha and IFN-gamma was also higher
      while that of IL-4 and IL-10 showed a decrease. For 36 h incubation, at low
      doses, relative increase in the expression of IL-4 and IL-10 was observed which
      decreased at higher doses, as did the expression of all other cytokines. The
      exhaustion of cytokine production at 36 h indicated that PBMCs became refractory
      to further stimulation. It can be concluded from this study that the cytokine
      response to sPGN initially was of Th2 type which skews, more pronouncedly, to Th1
      type with time till the cells become refractory to further stimulation. 

PMID- 25049660
TI  - Substantial Effect of Melanin Influencing Factors on In vitro Melanogenesis in
      Muzzle Melanocytes of Differently Colored Hanwoo.
AB  - The present study was designed to investigate the effect of alpha-melanocyte
      stimulating hormone (alpha-MSH), nitric oxide (NO) and L-cysteine on melanin
      production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle
      melanocytes of differently colored three native Hanwoo cattle. Muzzle samples
      were taken from black, brindle and brown Hanwoo and purified melanocytes were
      cultured with alpha-MSH, nitric oxide and L-cysteine at 100 nM, 50 uM and 0.07
      mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA
      expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. alpha-MSH and
      nitric oxide significantly increased (p<0.05) the amount of total melanin in
      black and brindle whereas eumelanin production in brown Hanwoo muzzle
      melanocytes. On the contrary, L-cysteine greatly (p<0.05) depressed the eumelanin
      production in black color but increased in brown. Simultaneously, up regulation
      of Tyr by nitric oxide and alpha-MSH and down regulation of Tyr, Tyrp-2 and MC1R
      genes by L-cysteine were observed in muzzle melanocytes of all three phenotypes.
      The results of this study revealed nitric oxide and alpha-MSH contribute hyper
      pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to
      pheomelanin production in different colored Hanwoo muzzle melanocytes. 

PMID- 25049661
TI  - Cytokines Expression and Nitric Oxide Production under Induced Infection to
      Salmonella Typhimurium in Chicken Lines Divergently Selected for Cutaneous
      Hypersensitivity.
AB  - In the present study, the impact of Salmonella Typhimurium on cell-mediated
      immunity (CMI) was investigated in 5 week-old immuno divergent broiler lines
      selected for the high and low response to phytohemagglutinin-P. The immune
      response was assessed in peripheral-blood mononuclear cells (PBMCs) induced with
      Salmonella Typhimurium at different time intervals (0 h, 0.5 h, 2 h, 4 h, 6 h, 12
      h and 24 h). The differential mRNA expression patterns of IFN-gamma, IL-2 and
      iNOS were evaluated by quantitative real time PCR. In-vitro production of nitric
      oxide (NO) was also estimated in the culture supernatant and correlated with iNOS
      mRNA expression. Present study showed higher production of NO in the high cell
      mediated line (HCMI) as compared to the low cell-mediated line (LCMI) upon
      stimulation with Salmonella Typhimurium. Correspondingly, higher mRNA expression
      of iNOS and IFN-gamma were observed in high response birds (HCMI); but IL-2 was
      down regulated in this line compared to the low response birds (LCMI).
      Significantly (p<0.05) higher expression of iNOS, IFN-gamma and higher production
      of NO in high line indicated that the selection for PHA-P response might be
      employed for increasing the immune competence against Salmonella Typhimurium in
      chicken flocks. 

PMID- 25049663
TI  - Effects of growth hormone gene polymorphism on lipogenic gene expression levels
      in diaphragm tissues of Japanese black heifers.
AB  - Two SNPs, i.e. L127V and T172M, of bovine growth hormone (GH) causing the
      presence of GH gene haplotypes A, B, and C was previously shown to alter
      intramuscular fatty acid (FA) composition in Japanese Black (JB) heifers. To
      determine the SNP effect on somatotropic hormone concentration and lipogenesis,
      we measured plasma GH, insulin, and insulin-like growth factor-1 (IGF-1)
      concentrations. We also measured mRNA levels of fatty acid synthase (FASN),
      stearoyl-coA desaturase (SCD), and sterol regulatory element binding proteins-1
      (SREBP-1) and FA composition in diaphragm tissues. Heifers with genotype CC had
      the lowest plasma insulin concentration and FASN and SCD mRNA levels among
      genotypes. FASN mRNA levels in haplotype A tended to positively correlate with
      saturated FA (SFA) content and negatively correlated with C18:2 and unsaturated
      FA (USFA) contents. SCD mRNA levels in haplotype A positively correlated with
      monounsaturated FA (MUFA) contents and negatively correlated with C18:0 content.
      They also tended to positively correlate with C16:1, C18:1, and USFA contents and
      USFA/SFA ratio and negatively correlate with SFA content. Taken together, GH gene
      polymorphism affects the lipogenic genes expression levels and their
      relationships with fatty acid compositions in diaphragm tissues of JB heifers at
      31 months of age. 

PMID- 25049662
TI  - Spatial Heterogeneity of Bacteria: Evidence from Hot Composts by Culture
      independent Analysis.
AB  - The phylogenetic diversity of the bacteria in hot composting samples collected
      from three spatial locations was investigated by molecular tools in order to
      determine the influence of gradient effect on bacterial communities during the
      thermophilic phase of composting swine manure with rice straw. Total microbial
      DNA was extracted and bacterial near full-length 16S rRNA genes were subsequently
      amplified, cloned, restriction fragment length polymorphism-screened and
      sequenced. The superstratum sample had the highest microbial diversity among the
      three samples which was possibly related to the surrounding conditions of the
      sample resulting from the location. The results showed that the sequences related
      to Bacillus sp. were most common in the composts. In superstratum sample, 45
      clones (33%) and 36 clones (27%) were affiliated with the Bacillus sp. and
      Clostridium sp., respectively; 74 clones (58%) were affiliated with the
      Clostridium sp. in the middle-level sample; 52 clones (40%) and 29 clones (23%)
      were affiliated with the Clostridium sp. and Bacillus sp. in substrate sample,
      respectively. It indicated that the microbial diversity and community in the
      samples were different for each sampling site, and different locations of the
      same pile often contained distinct and different microbial communities. 

PMID- 25049664
TI  - Estimation of Effective Population Size in the Sapsaree: A Korean Native Dog
      (Canis familiaris).
AB  - Effective population size (Ne) is an important measure to understand population
      structure and genetic variability in animal species. The objective of this study
      was to estimate Ne in Sapsaree dogs using the information of rate of inbreeding
      and genomic data that were obtained from pedigree and the Illumina CanineSNP20
      (20K) and CanineHD (170K) beadchips, respectively. Three SNP panels, i.e. Sap134
      (20K), Sap60 (170K), and Sap183 (the combined panel from the 20K and 170K), were
      used to genotype 134, 60, and 183 animal samples, respectively. The Ne estimates
      based on inbreeding rate ranged from 16 to 51 about five to 13 generations ago.
      With the use of SNP genotypes, two methods were applied for Ne estimation, i.e.
      pair-wise r (2) values using a simple expectation of distance and r (2) values
      under a non-linear regression with respective distances assuming a finite
      population size. The average pair-wise Ne estimates across generations using the
      pairs of SNPs that were located within 5 Mb in the Sap134, Sap60, and Sap183
      panels, were 1,486, 1,025 and 1,293, respectively. Under the non-linear
      regression method, the average Ne estimates were 1,601, 528, and 1,129 for the
      respective panels. Also, the point estimates of past Ne at 5, 20, and 50
      generations ago ranged between 64 to 75, 245 to 286, and 573 to 646,
      respectively, indicating a significant Ne reduction in the last several
      generations. These results suggest a strong necessity for minimizing inbreeding
      through the application of genomic selection or other breeding strategies to
      increase Ne, so as to maintain genetic variation and to avoid future bottlenecks
      in the Sapsaree population. 

PMID- 25049665
TI  - Lactation persistency as a component trait of the selection index and increase in
      reliability by using single nucleotide polymorphism in net merit defined as the
      first five lactation milk yields and herd life.
AB  - We first sought to clarify the effects of discounted rate, survival rate, and
      lactation persistency as a component trait of the selection index on net merit,
      defined as the first five lactation milks and herd life (HL) weighted by 1 and
      0.389 (currently used in Japan), respectively, in units of genetic standard
      deviation. Survival rate increased the relative economic importance of later
      lactation traits and the first five lactation milk yields during the first 120
      months from the start of the breeding scheme. In contrast, reliabilities of the
      estimated breeding value (EBV) in later lactation traits are lower than those of
      earlier lactation traits. We then sought to clarify the effects of applying
      single nucleotide polymorphism (SNP) on net merit to improve the reliability of
      EBV of later lactation traits to maximize their increased economic importance due
      to increase in survival rate. Net merit, selection accuracy, and HL increased by
      adding lactation persistency to the selection index whose component traits were
      only milk yields. Lactation persistency of the second and (especially) third
      parities contributed to increasing HL while maintaining the first five lactation
      milk yields compared with the selection index whose only component traits were
      milk yields. A selection index comprising the first three lactation milk yields
      and persistency accounted for 99.4% of net merit derived from a selection index
      whose components were identical to those for net merit. We consider that the
      selection index comprising the first three lactation milk yields and persistency
      is a practical method for increasing lifetime milk yield in the absence of data
      regarding HL. Applying SNP to the second- and third-lactation traits and HL
      increased net merit and HL by maximizing the increased economic importance of
      later lactation traits, reducing the effect of first-lactation milk yield on HL
      (genetic correlation (rG) = -0.006), and by augmenting the effects of the second-
      and third-lactation milk yields on HL (rG = 0.118 and 0.257, respectively). 

PMID- 25049666
TI  - Proteome Analysis of Bovine Longissimus dorsi Muscle Associated with the Marbling
      Score.
AB  - The breeding value of marbling score in skeletal muscle is an important factor
      for evaluating beef quality. In the present study, we investigated proteins
      associated with the breeding value of the marbling score for bovine sirloin to
      select potential biomarkers to improve meat quality through comparative proteomic
      analysis. Proteins isolated from muscle were separated by two-dimensional gel
      electrophoresis. After analyzing images of the stained gel, seven protein spots
      for the high marbling score group were identified corresponding to changes in
      expression that were at least two-fold compared to the low marbling score group.
      Four spots with increased intensities in the high marbling score group were
      identified as phosphoglycerate kinase 1, triosephophate isomerase, acidic
      ribosomal phosphoprotein PO, and capping protein (actin filament) Z-line alpha 2.
      Spots with decreased intensities in the high marbling score group compared to the
      low score group were identified as 14-3-3 epsilon, carbonic anhydrase II, and
      myosin light chain 1. Expression of myosin light chain 1 and carbonic anhydrase 2
      was confirmed by Western blotting. Taken together, these data could help improve
      the economic performance of cattle and provide useful information about the
      underlying the function of bovine skeletal muscle. 

PMID- 25049667
TI  - Tissues Expression, Polymorphisms Identification of FcRn Gene and Its
      Relationship with Serum Classical Swine Fever Virus Antibody Level in Pigs.
AB  - Neonatal Fc receptor (FcRn) gene encodes a receptor that binds the Fc region of
      monomeric immunoglobulin G (IgG) and is responsible for IgG transport and
      stabilization. In this report, the 8,900 bp porcine FcRn genomic DNA structure
      was identified and putative FcRn protein included 356 amino acids. Alignment and
      phylogenetic analysis of the porcine FcRn amino acid sequences with their
      homologies of other species showed high identity. Tissues expression of FcRn mRNA
      was detected by real time quantitative polymerase chain reaction (Q-PCR), the
      results revealed FcRn expressed widely in ten analyzed tissues. One single
      nucleotide polymorphism (SNP) (HQ026019:g.8526 C>T) in exon6 region of porcine
      FcRn gene was demonstrated by DNA sequencing analysis. A further analysis of SNP
      genotypes associated with serum Classical Swine Fever Virus antibody (anti-CSFV)
      concentration was performed in three pig populations including Large White,
      Landrace and Songliao Black pig (a Chinese indigenous breed). Our results of
      statistical analysis showed that the SNP had a highly significant association
      with the level of anti-CSFV antibody (At d 20; At d 35) in serum (p = 0.008; p =
      0.0001). Investigation of expression and polymorphisms of the porcine FcRn gene
      will help us in further understanding the molecular basis of the antibody
      regulation pathway in the porcine immune response. All these results indicate
      that FcRn gene might be regarded as a molecular marker for genetic selection of
      anti-CSFV antibody level in pig disease resistance breeding programmes. 

PMID- 25049668
TI  - Heat Shock Protein 70 Expression is Increased in the Liver of Neonatal
      Intrauterine Growth Retardation Piglets.
AB  - Intrauterine growth retardation (IUGR) leads to the dysfunction in digestive
      system, as well as the alteration in the expression of some functional proteins.
      Heat shock protein 70 (Hsp70) could be induced by various stress factors, but
      whether Hsp70 expression is changed in neonatal IUGR infants has not been
      demonstrated. This study was conducted to explore the expression of Hsp70 in the
      liver by using the IUGR piglet model. Liver and plasma samples were obtained from
      IUGR and normal birth weight (NBW) piglets at birth. The neonatal IUGR piglets
      had significantly lower liver weight than their counterparts. The activities of
      aspartate aminotransferase and alanine aminotransferase in serum were enhanced
      significantly in IUGR indicating liver dysfunction. The activities of superoxide
      dismutase (p<0.01), glutathione peroxidase (p<0.01) and catalase (p>0.05) were
      lower and the level of malondialdehybe was higher (p<0.05) in IUGR liver compared
      with in NBW. According to the results of histological tests, fatty hepatic
      infiltrates and cytoplasmic vacuolization were present in the liver of IUGR
      piglets, but not in NBW liver. The expression of Hsp70 protein was significantly
      higher (p<0.05) in IUGR piglet liver than in NBW. Similar to where the hepatic
      injuries were observed, location of Hsp70 was mostly in the midzonal hepatic
      lobule indicating that oxidative stress might be responsible for the increased
      expression of Hsp70. 

PMID- 25049669
TI  - Microarray Analysis of Gene Expression in the Uterine Endometrium during the
      Implantation Period in Pigs.
AB  - During embryo implantation in pigs, the uterine endometrium undergoes dramatic
      morphological and functional changes accompanied with dynamic gene expression.
      Since the greatest amount of embryonic losses occur during this period, it is
      essential to understand the expression and function of genes in the uterine
      endometrium. Although many reports have studied gene expression in the uterine
      endometrium during the estrous cycle and pregnancy, the pattern of global gene
      expression in the uterine endometrium in response to the presence of a conceptus
      (embryo/fetus and associated extraembryonic membranes) has not been completely
      determined. To better understand the expression of pregnancy-specific genes in
      the endometrium during the implantation period, we analyzed global gene
      expression in the endometrium on day (D) 12 and D15 of pregnancy and the estrous
      cycle using a microarray technique in order to identify differentially expressed
      endometrial genes between D12 of pregnancy and D12 of the estrous cycle and
      between D15 of pregnancy and D15 of the estrous cycle. Results showed that the
      global pattern of gene expression varied with pregnancy status. Among 23,937
      genes analyzed, 99 and 213 up-regulated genes and 92 and 231 down-regulated genes
      were identified as differentially expressed genes (DEGs) in the uterine
      endometrium on D12 and D15 of pregnancy compared to D12 and D15 of the estrous
      cycle, respectively. Functional annotation clustering analysis showed that those
      DEGs included genes involved in immunity, steroidogenesis, cell-to-cell
      interaction, and tissue remodeling. These findings suggest that the implantation
      process regulates differential endometrial gene expression to support the
      establishment of pregnancy in pigs. Further analysis of the genes identified in
      this study will provide insight into the cellular and molecular bases of the
      implantation process in pigs. 

PMID- 25049670
TI  - Reproductive Response of Ewes Fed with Taiwan Grass Hay (Pennisetum purpureum
      Schum.) Supplemented with Duckweed (Lemna sp. and Spirodela sp.).
AB  - The effect of duckweed (DW) supplementation was evaluated on dry matter intake
      (DMI), presence and duration of estrus, percentage of ewes repeating estrus and
      pregnancy rate, as well as the concentration of progesterone (P4) in multiparous
      crossbred ewes from Pelibuey, Dorper, and Katahdin breeds, fed with Taiwan grass
      hay (TWH). Eighteen ewes with 39.7+/-4 kg mean body weight, kept in individual
      pens, were randomly assigned to one of the following treatments: T1: TWH, T2: TWH
      plus 200 g DW, T3: TWH plus 300 g DW. The ewes were synchronized with 40 mg
      fluorogestone acetate (FGA) and 400 UI equine chorionic gonadotropin (eCG). Data
      were analyzed as a completely randomized design using the GLM procedure. DW
      supplementation had no effect on dry matter intake (p>0.05); however, a slight
      decrease of TWH intake was observed as DW supplementation increased. No
      differences (p>0.05) were found in the beginning of estrus, percentage of ewes
      presenting it, its duration, or pregnancy rate. There were no differences
      (p>0.05) on P4 concentration among treatments, or treatmentxperiod interaction
      (p>0.05). However the period was significant (p<0.01), since the P4 levels
      increased as time increased after the removal of the FGA device and eCG
      application. 

PMID- 25049671
TI  - Effect of ground corn cob replacement for cassava chip on feed intake, rumen
      fermentation and urinary derivatives in swamp buffaloes.
AB  - Four Thai - rumen fistulated male swamp buffaloes (Bubalus bubalis), about four
      years old with 400+/-20 kg liveweight, were randomly assigned according to a 4*4
      Latin square design to receive dietary treatments. The treatments were: ground
      corn cob (GCC) replacement for cassava chip (CC) in concentrate at 0% (T1); GCC
      replacement at 33% (T2); GCC replacement at 67% (T3); and GCC replacement at 100%
      (T4), respectively. During the experiment, concentrate was offered at 0.5% BW
      while 5% urea-treated rice straw was given at ad libitum. The result revealed
      that there was no effect of GCC replacement on DMI among treatments. In addition,
      digestibilities of DM, OM and CP were not different while aNDF linearly increased
      with an increasing level of GCC replacement. However, GCC replacement did not
      affect rumen fermentation such as ruminal pH, NH3-N and VFA concentration; except
      C3 proportion which was the highest at 33% replacement while the lowest was at
      100% replacement. All replacements of GCC resulted in similar protozoal and
      bacterial populations and microbial protein synthesis (MPS). Purine derivatives
      (PD) concentration in urine and PD to creatinine (PDC) index were varied with
      time of urination and among treatments at 0 to 8 and 8 to 16 h post feeding and
      higher values were shown among the GCC replacement groups. However at 16 to 24 h
      post feeding, it was untraceable. In addition, creatinine concentration was
      similar among all treatments at every sampling time. Based on the above results,
      GCC can be used as an energy source for swamp buffalo fed with rice straw. Spot
      sampling of urine can be used for purine derivatives determination. 

PMID- 25049672
TI  - Performance of Nursing Awassi Ewes Fed Different Levels of Bread By-product.
AB  - Objective of this experiment was to evaluate the effect of partial substitution
      of barley grain with bread by-product (BB) on performance of Awassi ewes and
      their lambs. Forty Awassi ewes rearing single lambs were randomly allotted into
      four experimental diets containing various levels of BB. The experimental diets
      contained 0 (BB0), 10 (BB10), 15 (BB15), and 20% (BB20) of BB on dietary dry
      matter (DM). The study lasted for eight weeks, in which the first week was used
      as an adaptation period and seven weeks of data collection. Ewes and their lambs
      were penned individually where they were fed their lactating diets ad libitum.
      Ewes and lambs body weights were measured at the beginning and at the end of the
      experiment. However, milk production and composition were evaluated biweekly.
      Feeding BB had no effect (p>0.05) on dry matter (DM), organic matter (OM), and
      crude protein (CP) intakes. However, neutral detergent fiber (NDF) intake was the
      lowest (p<0.05) for the BB20 and BB15 diets followed to BB10 diet (i.e., 640,
      677, 772 g/d, respectively) while the highest NDF intake was for the BB0 diet
      (i.e., 825 g/d). Similarly, NDF intake decreased linearly (p<0.001) as the BB
      content increased. Acid detergent fiber (ADF) intake was highest (p<0.05) for the
      BB0 and BB10 diets (425 and 416 g/d, respectively) followed by the BB15 and BB20
      diets (359 and 342 g/d, respectively). Moreover, a linear (p<0.001), quadratic (p
      = 0.04), and cubic (p = 0.04) effects were observed in ADF intake among diets.
      Nutrient digestibility was similar among different diets. Bread by-product had no
      effect (p>0.05) on ewes body weight change and on lamb performance (i.e., weaning
      body weight and average daily gain). Similarly, no differences (p>0.05) were
      observed either in milk production or composition by the BB substitution.
      Inclusion of BB reduced feed cost by 9, 14, and 18% for the BB10, BB15, and BB20
      diets, respectively. No differences were observed in milk efficiency (DM intake:
      milk production; p>0.05) among diets. However, cost of milk production ($US/kg
      milk) was the lowest (p<0.05) in the diet containing BB20. Results of the present
      study indicate that feeding bread by-product up to 20% of the diet DM had no
      effect on performance of Awassi ewes and their lambs and reduced feed cost. 

PMID- 25049673
TI  - Comparison of Growth Performance and Whole-body Amino Acid Composition in Red
      Seabream (Pagrus major) Fed Free or Dipeptide Form of Phenylalanine.
AB  - This study was conducted to evaluate the efficacy of the dipeptide form of
      phenylalanine as a new source of amino acid in terms of growth performance and
      whole-body amino acid composition in comparison to the free form for red seabream
      (Pagrus major). Fish (1.46+/-0.001 g) were fed four isonitrogenous and isocaloric
      experimental diets containing 0.7 or 1.4% phenylalanine either in free or
      dipeptide form. A feeding trial was carried out in three replicates and the fish
      were fed to apparent satiation for six weeks. At the end of the feeding trial,
      feed intake of fish was influenced by both phenylalanine form and level and
      significantly higher values were obtained at an inclusion level of 0.7% and by
      the use of dipeptide form. However, the other growth parameters did not
      significantly differ among treatments. Whole-body amino acid compositions
      revealed no significant changes in concentrations of both essential and non
      essential amino acids regardless of the increase in phenylalanine levels or the
      use of its different forms. The finding in this study indicates that juvenile red
      seabream can utilize dipeptide phenylalanine as efficiently as free form without
      any undesirable effects on growth performance or whole-body amino acid
      composition. 

PMID- 25049674
TI  - Nutritional and Hormonal Induction of Fatty Liver Syndrome and Effects of Dietary
      Lipotropic Factors in Egg-type Male Chicks.
AB  - This experiment was conducted with male chicks to investigate the influence of
      hormones and nutrients on the development of fatty liver syndrome (FLS) as well
      as the effects of dietary lipotropic factors on hepatic fat accumulation and
      lipogenic enzyme gene expression. A total of two-hundred sixteen 4-wk-old Hy-Line
      male chicks were divided into six groups and fed an experimental diet (T1, low
      energy diet with low levels of lipotropic factors; T2, high-energy diet with low
      levels of lipotropic factors; T3 and T5, low-energy diet with high levels of
      lipotropic factors; T4 and T6, high-energy diet with high levels of lipotropic
      factors) for six weeks. The chicks in T5 and T6 groups were treated with
      intramuscular injections of estradiol benzoate for three days prior to biopsy and
      clinical analysis of FLS. Chicks treated with estrogen had significantly greater
      liver weights than untreated chicks. The abdominal fat contents were increased in
      chicks consuming high-energy diets as compared to those consuming low-energy
      diets. Treatment with estrogen significantly increased the concentrations of
      serum cholesterol, triacylglycerol and phospholipid (p<0.05). The hepatic
      triacylglycerol levels were tenfold higher in the estrogen treated chicks than in
      the untreated chicks. There were no significant differences in malondialdehyde
      levels between the treatment groups. Estrogen treatment dramatically increased
      the levels of fatty acid synthetase, acetyl-CoA carboxylase and ApoB mRNA. The
      results indicated that treatment with exogenous estrogen in growing male chicks
      induced hepatic fat accumulation, which might be partially due to increased
      lipogenic enzyme gene expression. 

PMID- 25049675
TI  - Lactobacillus plantarum ZLP001: In vitro Assessment of Antioxidant Capacity and
      Effect on Growth Performance and Antioxidant Status in Weaning Piglets.
AB  - The objective of this study was to evaluate the antioxidant capacity of
      Lactobacillus plantarum ZLP001 and its effects on growth performance and
      antioxidant status in weaning piglets. The survival in hydrogen peroxide and free
      radical-scavenging activity of Lactobacillus plantarum ZLP001 were analysed in
      vitro. The Lactobacillus plantarum ZLP001 showed high viability in 1.0 mmol/L
      hydrogen peroxide and high scavenging ability against hydroxyl, superoxide anion,
      and DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals which was dose dependent.
      Ninety-six weaning piglets were selected (7.45+/-0.79 kg) and divided into three
      groups comprising of negative control without any supplementation, treatment
      group with supplemented 6.8*10(7) Lactobacillus plantarum ZLP001 CFU/g of diet,
      and positive control with antibiotic treatment (chlorotetracycline, 80 mg/kg
      diet). The results showed that Lactobacillus plantarum ZLP001 supplementation
      enhanced feed conversion rates in piglets compared with control (p<0.05).
      Supplementation of Lactobacillus plantarum ZLP001 increased the concentration of
      superoxide dismutase (p<0.05), glutathione peroxidase (p<0.01) and catalase in
      serum (p<0.10), while decreased the concentration of malondialdehyde (p<0.05).
      The present study implies that the strain Lactobacillus plantarum ZLP001 had high
      antioxidant ability and its supplementation improved the growth performance and
      antioxidant status of weaning piglets, so it can be considered useful to
      alleviate oxidative stress and increase productive performance of pigs. (Key
      Words: Probiotic, Antioxidant Capacity, Weaning Piglet). 

PMID- 25049676
TI  - Growth performance, meat yield, oxidative stability, and Fatty Acid composition
      of meat from broilers fed diets supplemented with a medicinal plant and
      probiotics.
AB  - The experiment was carried out to investigate the effects of Alisma canaliculatum
      with probiotics (ACP) on the growth performance, meat composition, oxidative
      stability, and fatty acid composition of broiler meat. Sixteen probiotic strains
      were tested for their levels of acid, bile, and heat tolerance. Among them,
      Lactobacillus acidophilus KCTC 3111, Enterococcus faecium KCTC 2022, Bacillus
      subtilis KCTC 3239, and Saccharomyces cerevisiae KCTC 7928 were selected for use
      in ACP. Exactly 140 Ross broiler chicks were assigned to four dietary treatments
      in five replications for 5 wks in a completely randomized design. The dietary
      treatments were NC (Negative control; basal diet), PC (Positive control; basal
      diet with 0.005% Chlortetracycline), ACP-0.5% (basal diet with 0.5% ACP powder),
      and ACP-1% (basal diet with 1% ACP powder). According to the results, body weight
      of the broilers increased, and feed conversion ratio improved in the ACP-0.5%
      group compared to the NC group (p<0.05). Crude protein content of breast meat was
      higher (p<0.05) in the ACP-0.5% group, whereas crude fat content of thigh meat
      was lower (p<0.05) in the supplemented groups. Breast meat absolute and relative
      weights were both higher (p<0.05) in the ACP groups compared to the control
      group. Further, ACP diets increased gizzard and decreased large intestine
      relative weights, whereas kidney relative weight decreased upon the addition of a
      higher level (1%) of ACP (p<0.05). Thiobarbituric acid reactive substances values
      of breast and thigh meats were reduced (p<0.05) by ACP supplementation compared
      to control. Regarding the fatty acid composition of breast meat, arachidonic
      acid, docosahexaenoic acid, PUFA, and n6 fatty acid levels decreased (p<0.05) in
      the ACP groups, whereas the levels of linoleic acid, PUFA, PUFA/SFA, and n6 fatty
      acid in thigh meat decreased (p<0.05) by ACP and PC diets. It can be suggested
      based on the study results that ACP-0.5% diet could be an effective feed additive
      for broilers. 

PMID- 25049677
TI  - Growth performance, meat quality and Fatty Acid metabolism response of growing
      meat rabbits to dietary linoleic Acid.
AB  - An experiment was conducted to determine the effects of different amounts of
      dietary linoleic acid (LA) on growth performance, serum biochemical traits, meat
      quality, fatty acids composition of muscle and liver, acetyl-CoA carboxylase
      (ACC) and carnitine palmitoyl transferase 1 (CPT 1) mRNA expression in the liver
      of 9 wks old to 13 wks old growing meat rabbits. One hundred and fifty 9 wks old
      meat rabbits were allocated to individual cages and randomly divided into five
      groups. Animals in each group were fed with a diet with the following LA addition
      concentrations: 0, 3, 6, 9 and 12 g/kg diet (as-fed basis) and LA concentrations
      were 0.84, 1.21, 1.34, 1.61 and 1.80% in the diet, respectively. The results
      showed as follows: the dietary LA levels significantly affected muscle color of
      LL included a* and b* of experimental rabbits (p<0.05). The linear effect of LA
      on serum high density lipoprotein cholesterol was obtained (p = 0.0119). The
      saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) contents of
      LL decreased and the polyunsaturated fatty acids (PUFAs) content of LL increased
      with dietary LA increase (p<0.0001). The PUFA n-6 content and PUFA n-3 content in
      the LL was significantly affected by the dietary LA levels (p<0.01, p<0.05). The
      MUFAs content in the liver decreased and the PUFAs contents in the liver
      increased with dietary LA increase (p<0.0001). The PUFA n-6 content and the PUFA
      n-6/n-3 ratio in the liver increased and PUFA n-3 content in the liver decreased
      with dietary LA increase (p<0.01). The linear effect of LA on CPT 1 mRNA
      expression in the liver was obtained (p = 0.0081). In summary, dietary LA
      addition had significant effects on liver and muscle fatty acid composition
      (increased PUFAs) of 9 wks old to 13 wks old growing meat rabbits, but had little
      effects on growth performance, meat physical traits and mRNA expression of liver
      relative enzyme of experimental rabbits. 

PMID- 25049678
TI  - Effect of eugenol and cinnamaldehyde on the growth performance, nutrient
      digestibility, blood characteristics, fecal microbial shedding and fecal noxious
      gas content in growing pigs.
AB  - A 5-wk trial with 96 ((Landrace* Yorkshire)*Duroc) pigs (BW = 26.56+/-0.42 kg)
      was conducted to investigate the effect of eugenol and cinnamaldehyde as feed
      additive in growing pigs. Pigs were assigned to 1 of 3 treatments in a randomized
      complete block design according to their sex and BW. Each treatment contained 8
      replications with 4 pigs (2 gilts and 2 barrows) per pen. Treatments included:
      control (basal diet; CON); (basal diet+1,000 mg eugenol/kg; ET); (basal
      diet+1,000 mg cinnamaldehyde/kg; CT). Administration of eugenol and
      cinnamaldehyde did not did not affect (p>0.05) the growth performance and
      apparent total tract digestibility. Dietary CT and ET led to a higher (p<0.05)
      lymphocyte concentration compared with CON. The inclusion of CT and ET decreased
      (p<0.05) the fecal E. coli concentration (p>0.05). Pigs fed the diets
      supplemented with eugenol and cinnamaldehyde had reduced (p<0.05) NH3 and H2S
      concentration throughout the experiment. In conclusion, results obtained in the
      present study indicated that supplementation of eugenol and cinamaldehyde had no
      effect on growth performance of pigs but exhibited lymphocyte-enhancing activity
      and decreased the fecal E. coli concentration and fecal noxious gas content (NH3
      and H2S). 

PMID- 25049679
TI  - Expression Profiling of WSSV ORF 199 and Shrimp Ubiquitin Conjugating Enzyme in
      WSSV Infected Penaeus monodon.
AB  - White spot syndrome virus (WSSV) is one of the major viral pathogens affecting
      shrimp aquaculture. Four proteins, WSSV199, WSSV 222, WSSV 249 and WSSV 403, from
      WSSV are predicted to encode a RING-H2 domain, which in presence of ubiquitin
      conjugating enzyme (E2) in shrimp can function as viral E3 ligase and modulate
      the host ubiquitin proteasome pathway. Modulation of host ubiquitin proteasome
      pathway by viral proteins is implicated in viral pathogenesis. In the present
      study, a time course expression profile analysis of WSSV Open Reading Frame (ORF)
      199 and Penaeus monodon ubiquitin conjugating enzyme (PmUbc) was carried out at
      0, 3, 6, 12, 24, 48 and 72 h post WSSV challenge by semi-quantitative RT-PCR as
      well as Real Time PCR. EF1alpha was used as reference control to normalize the
      expression levels. A significant increase in PmUbc expression at 24 h post
      infection (h.p.i) was observed followed by a decline till 72 h.p.i. Expression of
      WSSV199 was observed at 24 h.p.i in WSSV infected P. monodon. Since the up
      regulation of PmUbc was observed at 24 h.p.i where WSSV199 expression was
      detected, it can be speculated that these proteins might interact with host
      ubiquitination pathway for viral pathogenesis. However, further studies need to
      be carried out to unfold the molecular mechanism of interaction between host and
      virus to devise efficient control strategies for this chaos in the shrimp culture
      industry. 

PMID- 25049680
TI  - Comparative Analysis on Antioxidative Ability of Muscle between Laiwu Pig and
      Large White.
AB  - This study was conducted to evaluate effects of storage temperatures (4 degrees C
      and 20 degrees C) and pig breeds (Laiwu pig and Large White pig) on the main
      antioxidative enzymes (superoxide dismutase, catalase, and glutathione
      peroxidase) activity and lipid oxidation in porcine Longissimus dorsi muscle.
      Activities of antioxidative enzymes (AOE) decreased slightly during storage,
      regardless of storage temperatures. Muscle antioxidative enzymes activities
      stored at 4 degrees C were higher than that stored at 20 degrees C. Laiwu pig's
      enzymes activities were significantly (p<0.01) higher than Large White's. The
      level of malondialdehyde is a direct expression of the grade of lipid oxidation
      in meat. In our study, the malondialdehyde contents increased after 6 days
      storage. However, malondialdehyde contents of Laiwu pig were significantly
      (p<0.01) lower than Large White's. A lower content of malondialdehyde corresponds
      to a lower oxidation of lipids. These results indicated the muscle antioxidative
      ability of Laiwu pig was higher than Large White pig. It also implied that
      antioxidative enzymes were involved in the essentials and deciding mechanisms of
      meat quality by quenching oxygen free radicals and inhibiting lipid oxidation in
      muscle. 

PMID- 25049681
TI  - Effect of Rapid Chilling on Beef Quality and Cytoskeletal Protein Degradation in
      M. longissimus of Chinese Yellow Crossbred Bulls.
AB  - The objective of this study was to investigate the effect of rapid chilling (RC)
      on beef quality and the degradation of cytoskeletal proteins. Twenty Chinese
      Yellow crossbred bulls were selected and randomly divided into two groups. RC and
      conventional chilling (CC) were applied to left and right sides of the carcasses
      respectively after slaughtering. To determine whether electrical stimulation (ES)
      treatment can alleviate the potential hazard of RC on meat quality, ES was
      applied to one group. The effects of RC and ES were determined by meat color,
      shear force and cytoskeletal protein degradation postmortem (PM). The results
      showed that RC decreased beef tenderness at 1 d and 3 d postmortem, but had no
      detrimental effect on meat color. Western blotting showed that RC decreased the
      degradation rate of desmin and troponin-T, but the effects weakened gradually as
      postmortem aging extended. Degradation rates of both desmin and troponin-T were
      accelerated by ES. The combination of RC and ES could improve beef color,
      accelerate degradation rate of cytoskeletal protein and improve beef tenderness. 

PMID- 25049682
TI  - Determination of Genetic Diversity among Korean Hanwoo Cattle Based on Physical
      Characteristics.
AB  - This study was conducted to establish genetic criteria for phenotypic
      characteristics of Hanwoo cattle based on allele frequencies and genetic variance
      analysis using microsatellite markers. Analysis of the genetic diversity among
      399 Hanwoo cattle classified according to nose pigmentation and coat color was
      carried out using 22 microsatellite markers. The results revealed that the
      INRA035 locus was associated with the highest Fis (0.536). Given that the Fis
      value for the Hanwoo INRA035 population ranged from 0.533 (white) to 1.000 (white
      spotted), this finding was consistent with the loci being fixed in Hanwoo cattle.
      Expected heterozygosities of the Hanwoo groups classified by coat colors and
      degree of nose pigmentation ranged from 0.689+/-0.023 (Holstein) to 0.743+/-0.021
      (nose pigmentation level of d). Normal Hanwoo and animals with a mixed white coat
      showed the closest relationship because the lowest DA value was observed between
      these groups. However, a pair-wise differentiation test of Fst showed no
      significant difference among the Hanwoo groups classified by coat color and
      degree of nose pigmentation (p<0.01). Moreover, results of the neighbor-joining
      tree based on a DA genetic distance matrix within 399 Hanwoo individuals and
      principal component analyses confirmed that different groups of cattle with mixed
      coat color and nose pigmentation formed other specific groups representing Hanwoo
      genetic and phenotypic characteristics. The results of this study support a
      relaxation of policies regulating bull selection or animal registration in an
      effort to minimize financial loss, and could provide basic information that can
      be used for establishing criteria to classify Hanwoo phenotypes. 

PMID- 25049683
TI  - Somatic Cells Count and Its Genetic Association with Milk Yield in Dairy Cattle
      Raised under Thai Tropical Environmental Conditions.
AB  - Somatic cells count (SCC), milk yield (MY) and pedigree information of 2,791
      first lactation cows that calved between 1990 and 2010 on 259 Thai farms were
      used to estimate genetic parameters and trends for SCC and its genetic
      association with MY. The SCC were log-transformed (lnSCC) to make them normally
      distributed. An average information-restricted maximum likelihood procedure was
      used to estimate variance components. A bivariate animal model that considered
      herd-yr-season, calving age, and regression additive genetic group as fixed
      effects, and animal and residual as random effects was used for genetic
      evaluation. Heritability estimates were 0.12 (SE = 0.19) for lnSCC, and 0.31 (SE
      = 0.06) for MY. The genetic correlation estimate between lnSCC and MY was 0.26
      (SE = 0.59). Mean yearly estimated breeding values during the last 20 years
      increased for SCC (49.02 cells/ml/yr, SE = 26.81 cells/ml/yr; p = 0.08), but not
      for MY (0.37 kg/yr, SE = 0.87 kg/yr; p = 0.68). Sire average breeding values for
      SCC and MY were higher than those of cows and dams (p<0.01). Heritability
      estimates for lnSCC and MY and their low but positive genetic correlation
      suggested that selection for low SCC may be feasible in this population as it is
      in other populations of dairy cows. Thus, selection for high MY and low SCC
      should be encouraged in Thai dairy improvement programs to increase profitability
      by improving both cow health and milk yield. 

PMID- 25049684
TI  - Effect of Population Reduction on mtDNA Diversity and Demographic History of
      Korean Cattle Populations.
AB  - The population sizes of three Korean indigenous cattle populations have been
      drastically reduced over the past decades. In this study, we examined the extent
      to which reduction in populations influenced genetic diversity, population
      structure and demographic history using complete mitochondrial DNA (mtDNA)
      control region sequences. The complete mtDNA control region was sequenced in 56
      individuals from Korean Black (KB), Jeju Black (JEB) and Korean Brindle (BRI)
      cattle populations. We included 27 mtDNA sequences of Korean Brown (BRO) from the
      GenBank database. Haplotype diversity estimate for the total population was high
      (0.870) while nucleotide diversity was low (0.004). The KB showed considerably
      low nucleotide (pi = 0.001) and haplotype (h = 0.368) diversities. Analysis of
      molecular variance revealed a low level of genetic differentiation but this was
      highly significant (p<0.001) among the cattle populations. Of the total genetic
      diversity, 7.6% was attributable to among cattle populations diversity and the
      rest (92.4%) to differences within populations. The mismatch distribution
      analysis and neutrality tests revealed that KB population was in genetic
      equilibrium or decline. Indeed, unless an appropriate breeding management
      practice is developed, inbreeding and genetic drift will further impoverish
      genetic diversity of these cattle populations. Rational breed development and
      conservation strategy is needed to safeguard these cattle population. 

PMID- 25049685
TI  - Effects of kisspeptin-10 on lipid metabolism in cultured chicken hepatocytes.
AB  - Our previous studies showed that kisspeptin-10 (Kp-10) injected in vivo can
      markedly increase lipid anabolism in liver of quails. In order to investigate the
      direct effect of Kp-10 on lipid metabolism of hepatocytes in birds, cells were
      separated from embryos livers and cultured in vitro with 0, 100 and 1,000 nM Kp
      10, respectively. The results showed that after 24 h treatment, cells viability
      was not affected by 100 nM Kp-10, but showed a mild decrease with 1,000 nM Kp-10
      compared to the control cells. Based on the results of the cell viability, 100 nM
      dosage of Kp-10 was selected for the further study and analysis. Compared with
      control cells, total cholesterol (Tch) contents in 100 nM treated cells were
      increased by 51.23%, but did not reach statistical significance, while the level
      of triglyceride (TG), high density of lipoprotein-cholesterol (HDL-C) and low
      density of lipoprotein-cholesterol (LDL-C) were significantly increased. Real
      time PCR results showed that ApoVLDL-II mRNA expression had a tendency to
      increase, genes including sterol regulatory element-binding protein-1 (SREBP-1),
      acetyl coenzyme A carboxylase alpha (ACCalpha), carnitine palmitoyltransferase 1
      (CPT1), 3-hydroxyl-3-methylglutaryl-coenzyme A reductases (HMGCR) and stearyl
      coenzyme A dehydrogenase-1 (SCD1) mRNA in hepatocytes were significantly down
      regulated by 100 nM Kp-10. However, contrary to its gene expression, SREBP-1
      protein expression was significantly up-regulated by 100 nM Kp-10. Some of the
      significant correlations in mRNA expression were found between genes encoding
      hepatic factors or enzymes involved in lipid metabolism in liver of birds. These
      results indicate that Kp-10 stimulates lipid synthesis directly in primary
      cultured hepatocytes of chickens. 

PMID- 25049686
TI  - Evaluation of a nutrition model in predicting performance of vietnamese cattle.
AB  - The objective of this study was to evaluate the predictions of dry matter intake
      (DM) and average daily gain (ADG) of Vietnamese Yellow (Vang) purebred and
      crossbred (Vang with Red Sindhi or Brahman) bulls fed under Vietnamese conditions
      using two levels of solution (1 and 2) of the large ruminant nutrition system
      (LRNS) model. Animal information and feed chemical characterization were obtained
      from five studies. The initial mean body weight (BW) of the animals was 186, with
      standard deviation +/-33.2 kg. Animals were fed ad libitum commonly available
      feedstuffs, including cassava powder, corn grain, Napier grass, rice straw and
      bran, and minerals and vitamins, for 50 to 80 d. Adequacy of the predictions was
      assessed with the Model Evaluation System using the root of mean square error of
      prediction (RMSEP), accuracy (Cb), coefficient of determination (r(2)), and mean
      bias (MB). When all treatment means were used, both levels of solution predicted
      DMI similarly with low precision (r(2) of 0.389 and 0.45 for level 1 and 2,
      respectively) and medium accuracy (Cb of 0.827 and 0.859, respectively). The LRNS
      clearly over-predicted the intake of one study. When this study was removed from
      the comparison, the precision and accuracy considerably increased for the level 1
      solution. Metabolisable protein was limiting ADG for more than 68% of the
      treatment averages. Both levels differed regarding precision and accuracy. While
      level 1 solution had the least MB compared with level 2 (0.058 and 0.159 kg/d,
      respectively), the precision was greater for level 2 than level 1 (0.89 and 0.70,
      respectively). The accuracy (Cb) was similar between level 1 and level 2 (p =
      0.8997; 0.977 and 0.871, respectively). The RMSEP indicated that both levels were
      on average under- or over-predicted by about 190 g/d, suggesting that even though
      the accuracy (Cb) was greater for level 1 compared to level 2, both levels are
      likely to wrongly predict ADG by the same amount. Our analyses indicated that the
      level 1 solution can predict DMI reasonably well for this type of animal, but it
      was not entirely clear if animals consumed at their voluntary intake and/or if
      the roughness of the diet decreased DMI. A deficit of ruminally-undegradable
      protein and/or a lack of microbial protein may have limited the performance of
      these animals. Based on these evaluations, the LRNS level 1 solution may be an
      alternative to predict animal performance when, under specific circumstances, the
      fractional degradation rates of the carbohydrate and protein fractions are not
      known. 

PMID- 25049687
TI  - The effects of additives in napier grass silages on chemical composition, feed
      intake, nutrient digestibility and rumen fermentation.
AB  - The effect of silage additives on ensiling characteristics and nutritive value of
      Napier grass (Pennisetum purpureum) silages was studied. Napier grass silages
      were made with no additive, fermented juice of epiphytic lactic acid bacteria
      (FJLB), molasses or cassava meal. The ensiling characteristics were determined by
      ensiling Napier grass silages in airtight plastic pouches for 2, 4, 7, 14, 21 and
      45 d. The effect of Napier grass silages treated with these additives on
      voluntary feed intake, digestibility, rumen fermentation and microbial rumen
      fermentation was determined in 4 fistulated cows using 4*4 Latin square design.
      The pH value of the treated silages rapidly decreased, and reached to the lowest
      value within 7 d of the start of fermentation, as compared to the control. Lactic
      acid content of silages treated with FJLB was stable at 14 d of fermentation and
      constant until 45 d of ensiling. At 45 d of ensiling, neutral detergent fiber
      (NDF) and acid detergent fiber (ADF) of silage treated with cassava meal were
      significantly lower (p<0.05) than the others. In the feeding trial, the intake of
      silage increased (p<0.05) in the cow fed with the treated silage. Among the
      treatments, dry matter intake was the lowest in the silage treated with cassava
      meal. The organic matter, crude protein and NDF digestibility of the silage
      treated with molasses was higher than the silage without additive and the silage
      treated with FJLB. The rumen parameters: ruminal pH, ammonia-nitrogen (NH3-N),
      volatile fatty acid (VFA), blood urea nitrogen (BUN) and bacterial populations
      were not significantly different among the treatments. In conclusion, these
      studies confirmed that the applying of molasses improved fermentative quality,
      feed intake and digestibility of Napier grass. 

PMID- 25049688
TI  - Effects of probiotic and prebiotic on average daily gain, fecal shedding of
      Escherichia coli, and immune system status in newborn female calves.
AB  - Thirty two Holstein female calves (initial body weight = 40+/-3.0 kg) were used
      to investigate the effects of probiotic and prebiotic on average daily gain
      (ADG), fecal E. coli count, white blood cell count, plasma IgG1 level and cell
      mediated immune response to injection of phytohemagglutinin in suckling female
      calves. Calves were assigned randomly to one of the four treatments, including
      whole milk without additives (control), whole milk containing probiotic, whole
      milk containing prebiotic and whole milk containing probiotic and prebiotic
      (synbiotic). Average daily gain was greater in calves fed probiotic, prebiotic
      and synbiotic at weeks 6, 7 and 8 (p<0.05). E. coli count was significantly lower
      in calves fed probiotic, prebiotic and synbiotic on d 56 (p<0.05). There was no
      significant difference between treatments in blood samples and cell-mediated
      response. This study showed that addition of probiotic, prebiotic and combination
      of these additives to milk enhanced ADG and reduced fecal E. coli count in
      preruminant calves. 

PMID- 25049689
TI  - Effect of Vitamin E Supplementation on Hematological and Plasma Biochemical
      Parameters during Long Term Exposure of Arsenic in Goats.
AB  - The present investigation was designed to determine whether supplementation of
      different level of vitamin E for 12 months to arsenic exposed goats (50 ppm as
      sodium arsenite) affords protection against the blood hemato-biochemical
      parameters caused by the metalloid. A total of 24 crossbred (Alpine*Beetal)
      lactating goats were assigned randomly into 4 equal groups (control, T1, T2 and
      T3) of 6 in each, on the basis of average body weight (36.10+/-0.11 kg) and milk
      yield (1.61+/-0.04 kg/d). The animals in T1, T2 and T3 were given 50 ppm arsenic,
      while in T2 and T3, additionally; vitamin E at the rate of 100 IU and 150 IU/kg
      dry matter (DM) respectively was additionally supplemented for the period of 12
      months. Hemoglobin (Hb), total leukocyte (TLC) and blood lymphocyte % were
      decreased (p<0.05) in arsenic fed groups and vitamin E supplementation in the
      experimental group showed a protective potential. Significant increases (p<0.05)
      in aspertate transaminase (AST) and alanine transaminase (ALT) activities among
      arsenic supplemented groups were recorded, however vitamin E supplementation at
      higher doses showed a protective effect (p<0.05) against AST but in the case of
      ALT no ameliorating effect was found in either of the doses. Plasma total protein
      was decreased (p>0.05) but creatinine level was periodically increased in all As
      supplemented groups and vitamin E supplementation did not produce any protective
      effect. It can be concluded that arsenic exposure resulted in varying degree of
      changes in hemato-biochemical parameters and activities of antioxidant enzymes in
      goats but concomitant treatment with Vitamin E is partially helpful in reducing
      the burden of arsenic induced effect. 

PMID- 25049690
TI  - Soluble Non-ammonia Nitrogen in Ruminal and Omasal Digesta of Korean Native
      Steers Supplemented with Soluble Proteins.
AB  - An experiment was conducted to study the effect of soluble protein supplements on
      concentration of soluble non-ammonia nitrogen (SNAN) in the liquid phase of
      ruminal (RD) and omasal digesta (OD) of Korean native steers, and to investigate
      diurnal pattern in SNAN concentration in RD and OD. Three ruminally cannulated
      Korean native steers in a 3*3 Latin square design consumed a basal diet of rice
      straw and corn-based concentrate (control), and that supplemented (kg/d DM basis)
      with intact casein (0.24; IC) or acid hydrolyzed casein (0.46; AHC). Ruminal
      digesta was sampled using a vacuum pump, whereas OD was collected using an omasal
      sampling system at 2.0 h intervals after a morning feeding. The SNAN fractions
      (free amino acid (AA), peptide and soluble protein) in RD and OD were assessed
      using the ninhydrin assay. Concentrations of free AA and total SNAN in RD were
      significantly (p<0.05) lower than those in OD. Although free AA concentration was
      relatively high, mean peptide was quantitatively the most important fraction of
      total SNAN in both RD and OD, indicating that degradation of peptide to AA rather
      than hydrolysis of soluble protein to peptide or deamination may be the most
      limiting step in rumen proteolysis of Korean native steers. Diurnal variation in
      peptide concentration in OD for the soluble protein supplemented diets during the
      feeding cycle peaked 2 h post-feeding and decreased thereafter whereas that for
      the control was relatively constant during the entire feeding cycle. Diurnal
      variation in peptide concentration was rather similar between RD and OD. 

PMID- 25049691
TI  - Hematological Responses, Survival, and Respiratory Exchange in the Olive
      Flounder, Paralichthys olivaceus, during Starvation.
AB  - A 12-wk experiment was conducted to examine the hematological changes, survival,
      and respiratory exchange in the olive flounder, Paralichthys olivaceus, during
      starvation. The growth, survival and respiratory exchange rates of the starved
      group were lower than those of the fed group during the experiment. Blood
      analysis, including hematocrit, hemoglobin, red blood cells, mean corpuscular
      hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular
      volume, did not differ significantly (p>0.05) between the fed and starved groups
      at the end of the experiment. There were no significant differences in plasma
      cortisol, glucose, Na(+), Cl(-), K(+), or aspartate aminotransferase between the
      fed and starved groups (p>0.05). Alanine aminotransferase levels were higher in
      the starved group than in the fed group, whereas plasma osmolality was lower in
      the starved group than in the fed group. It was shown that starved fish had
      various problems after four weeks, which did not occur in the fed group. Long
      term starvation is infrequent in aquaculture farms. However, starvation studies
      of this kind are very useful for a basic understanding of how physiological
      changes affect fish health, life expectancy, and growth. 

PMID- 25049692
TI  - The Bacillus subtilis and Lactic Acid Bacteria Probiotics Influences Intestinal
      Mucin Gene Expression, Histomorphology and Growth Performance in Broilers.
AB  - The aim of the present study was to evaluate the effect of commercial monostrain
      and multistrain probiotics in diets on growth performance, intestinal morphology
      and mucin gene (MUC2) expression in broiler chicks. Three hundred seventy-eight 1
      d-old male Arian broiler chicks were allocated in 3 experimental groups for 6 wk.
      The birds were fed on a corn-soybean based diet and depending on the addition
      were labeled as follows: control-unsupplemented (C), birds supplemented with
      Bacillus subtilis (BS) and lactic acid bacteria (LAB) based probiotics. Each
      treatment had 6 replicates of 21 broilers each. Treatment effects on body weight,
      feed intake, feed conversion ratio and biomarkers such as intestinal goblet cell
      density, villus length, villus width, and mucin gene expression were determined.
      Total feed intake did not differ significantly between control birds and those
      fed a diet with probiotics (p>0.05). However, significant differences in growth
      performance were found. Final body weight at 42 d of age was higher in birds fed
      a diet with probiotics compared to those fed a diet without probiotic (p<0.05).
      Inclusion of Bacillus subtilis based probiotic in the diets also significantly
      affected feed conversion rate (FCR) compared with control birds (p<0.05). No
      differences in growth performance were observed in birds fed different types of
      probiotic supplemented diets. Inclusion of lactic acid bacteria based probiotic
      in the diets significantly increased goblet cell number and villus length
      (p<0.05). Furthermore, diets with Bacillus subtilis based probiotics
      significantly increased gene expression (p<0.05), with higher intestinal MUC2
      mRNA in birds fed diet with probiotics compared to those fed the control diet. In
      BS and LAB probiotic fed chicks, higher growth performance may be related to
      higher expression of the MUC2 gene in goblet cells and/or morphological change of
      small intestinal tract. The higher synthesis of the mucin gene after probiotic
      administration may positively affect bacterial interactions in the intestinal
      digestive tract, intestinal mucosal cell proliferation and consequently efficient
      nutrient absorption. 

PMID- 25049693
TI  - Evaluation of the effect of low dietary fermentable carbohydrate content on
      growth performance, nutrient digestibility, blood characteristics, and meat
      quality in finishing pigs.
AB  - A total of 96 pigs (49.23+/-3.20 kg) were used in an 11 wk growth trial to
      evaluate the effect of fermentable carbohydrate (FC) content on growth
      performance, apparent total tract digestibility (ATTD) of nutrient, blood
      profile, and meat quality. The dietary treatments were: i) negative control (NC),
      basal diet, ii) positive control (PC), NC+antibiotics (positive control diet with
      5 ppm flavomycin), iii) PCL, PC-13% lower FC, and iv) NCL, NC-13% lower FC. The
      growth performance (average daily gain, average daily feed intake, and gain/feed)
      didn't differ among treatments through the whole experiment. These pigs fed the
      PCL diet had the greater (p<0.05) apparent total tract digestibility (ATTD) of
      dry matter than those from PC and NC treatment at the end of the experiment. No
      differences were observed in white blood cell (WBC), red blood cell (RBC), and
      lymphocyte concentration among different treatments. After the feeding period,
      meat samples were collected from the pigs at slaughter. The pigs in NCL and PCL
      treatments had greater (p<0.05) backfat thickness and lower lean percentage. The
      color value of loin was higher (p<0.05) in NCL treatment compared to PCL
      treatment. Also, the NCL treatment had higher (p<0.05) marbling value than PC
      treatment. The drip loss was depressed by PCL and NCL treatment comapared to NC
      treatments. The water holding capacity (WHC) was higher (p<0.05) in NC and PCL
      treatment. In conclusion, the low FC can improve digestibility and meat quality
      of finishing pigs. 

PMID- 25049694
TI  - Effect of 24 h Fasting on Gene Expression of AMPK, Appetite Regulation Peptides
      and Lipometabolism Related Factors in the Hypothalamus of Broiler Chicks.
AB  - The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key part of a
      kinase-signaling cascade that acts to maintain energy homeostasis. The objective
      of this experiment was to investigate the possible effects of fasting and
      refeeding on the gene expression of hypothalamic AMPK, some appetitive regulating
      peptides and lipid metabolism related enzymes. Seven-day-old male broiler (Arbor
      Acres) chicks were allocated into three equal treatments: fed ad libitum
      (control); fasted for 24 h; fasted for 24 h and then refed for 24 h. Compared
      with the control, the hypothalamic gene expression of AMPKalpha2, AMPKbeta1,
      AMPKbeta2, AMPKgamma1, Ste20-related adaptor protein beta (STRADbeta), mouse
      protein 25alpha (MO25alpha) and agouti-related peptide (AgRP) were increased
      after fasting for 24 h. No significant difference among treatments was observed
      in mRNA levels of AMPKalpha1, AMPKgamma2, LKB1 and neuropeptide Y (NPY). However,
      the expression of MO25beta, pro-opiomelanocortin (POMC), corticotropin-releasing
      hormone (CRH), ghrelin, fatty acid synthase (FAS), acetyl-CoA carboxylase alpha
      (ACCalpha), carnitine palmitoyltransferase 1 (CPT-1) and sterol regulatory
      element binding protein-1 (SREBP-1) were significantly decreased. The present
      results indicated that 24 h fasting altered gene expression of AMPK subunits,
      appetite regulation peptides and lipometabolism related factors in chick's
      hypothalamus; the hypothalamic FAS signaling pathway might be involved in the
      AMPK regulated energy homeostasis and/or appetite regulation in poultry. 

PMID- 25049695
TI  - Influences of phytoncide supplementation on growth performance, nutrient
      digestibility, blood profiles, diarrhea scores and fecal microflora shedding in
      weaning pigs.
AB  - A total of 140 weaning pigs ((Landrace*Yorkshire)*Duroc, BW = 6.47+/-0.86 kg)
      were used in a 5-wk growth trail to determine the effects of phytoncide
      supplementation on growth performance, nutrient apparent total tract
      digestibility (ATTD), blood profiles, diarrhea scores and fecal microflora
      shedding. Pigs were assigned randomly by BW into 5 treatments, dietary treatments
      were: i) NC, basal diet; ii) PC, NC+0.05% tylosin; iii) EO, NC+0.1% essential
      oil; iv) PP, NC+0.2% PP (phytoncide with 2% citric acid), and v) PA, NC+0.2% PA
      (phytoncide). Each treatment had 7 replicate pens with 4 pigs per pen. All pigs
      were housed in pens with a self-feeder and nipple drinker to allow ad libitum
      access to feed and water throughout the experimental period. During 0 to 2 wks,
      supplementation with essential oil and PA decreased (p<0.05) G/F compared with
      the other treatments. During 2 to 5 wks, supplementation with PA led to a higher
      (p<0.05) G/F than the other treatments. At 2 wk, ATTD of dry matter (DM) and
      gross energy (GE) in EO treatment were decreased (p<0.05) compared with NC
      treatment. Dietary PC treatment improved (p<0.05) ATTD of DM and E compared with
      the CON group, and PA and PP treatments showed a higher (p<0.05) ATTD of E than
      that in NC treatment. Pigs fed phytoncide (PA and PP) had a greater (p<0.05) ATTD
      of DM than those of NC and EO treatments at 5 wk. Moreover, supplementation with
      phytoncide elevated (p<0.05) the concentration of immunoglobulin (IgG) in blood
      at 2 wk. The inclusion of EO, PP and PA treatments showed a greater (p<0.05)
      amount of fecal Lactobacillus compared with CON group. However, no difference
      (p>0.05) was observed in diarrhea scores among treatments. In conclusion,
      phytoncide can elevate feed efficiency, nutrient digestibility, and improve the
      fecal Lactobacillus counts in weaning pigs. Our results indicated that the
      phytoncide could be used as a good antibiotics alternative in weaning pigs. 

PMID- 25049696
TI  - The Regulation of Chemerin and CMKLR1 Genes Expression by TNF-alpha, Adiponectin,
      and Chemerin Analog in Bovine Differentiated Adipocytes.
AB  - Adipokines, adipocyte-derived protein, have important roles in various kinds of
      physiology including energy homeostasis. Chemerin, one of adipocyte-derived
      adipokines, is highly expressed in differentiated adipocytes and is known to
      induce macrophage chemotaxis and glucose intolerance. The objective of the
      present study was to investigate the changes of chemerin and the chemokine-like
      receptor 1 (CMKLR1) gene expression levels during differentiation of the bovine
      adipocyte and in differentiated adipocytes treated with tumor necrosis factor
      alpha (TNF-alpha), adiponectin, leptin, and chemerin (peptide analog). The
      expression levels of the chemerin gene increased at d 6 and 12 of the
      differentiation period accompanied by increased cytoplasm lipid droplets. From d
      6 onward, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene
      expression levels were significantly higher than that of d 0 and 3. In contrast,
      CMKLR1 expression levels decreased at the end of the differentiation period. In
      fully differentiated adipocytes (i.e. at d 12), the treatment of TNF-alpha and
      adiponectin upregulated both chemerin and CMKLR1 gene expression levels, although
      leptin did not show such effects. Moreover, chemerin analog treatment was shown
      to upregulate chemerin gene expression levels regardless of doses. These results
      suggest that the expression of chemerin in bovine adipocyte might be regulated by
      chemerin itself and other adipokines, which indicates its possible role in
      modulating the adipokine secretions in adipose tissues. 

PMID- 25049697
TI  - Increases of antibiotic resistance in excessive use of antibiotics in smallholder
      dairy farms in northern Thailand.
AB  - Antibiotic resistance patterns of bacterial isolates from both quarter teat-tip
      swabs and their quarter milk samples were evaluated in smallholder dairy farms in
      northern Thailand with excessive use of antibiotics (HIGH) compared with normal
      use (NORM). Results from teat-tip swab samples showed that the percentage of
      Bacillus spp. resistance to overall antibiotics was significantly lower in the
      NORM group than that of the HIGH group, whereas, the resistance percentage of
      coagulase-negative staphylococci in the NORM group was higher than that of the
      HIGH one. The overall mastitis-causing bacteria isolated from milk samples were
      environmental streptococci (13.8%), coagulase-negative staphylococci (9.9%),
      Staphylococcus aureus (5.4%), and Corynebacterium bovis (4.5%). Both
      staphylococci and streptococci had significantly higher percentages of resistance
      to cloxacillin and oxacillin in the HIGH group when compared to the NORM one. An
      occurrence of vancomycin-resistant bacteria was also observed in the HIGH group.
      In conclusion, the smallholder dairy farms with excessive use of antibiotics had
      a higher probability of antibiotic-resistant pattern than the farms with normal
      use. 

PMID- 25049698
TI  - Effects of Purple-fleshed Sweet Potato (Ipomoera batatas Cultivar Ayamurasaki)
      Powder Addition on Color and Texture Properties and Sensory Characteristics of
      Cooked Pork Sausages during Storage.
AB  - This study was conducted to evaluate the effects of adding purple-fleshed sweet
      potato (PFP) powder on the texture properties and sensory characteristics of
      cooked pork sausage. Sodium nitrite alone and sodium nitrite in combination with
      PFP were added to five different treatments sausages (CON (control) = 0.01%
      sodium nitrite, SP25 = 0.005% sodium nitrite and 0.25% purple-fleshed sweet
      potato powder combination, SP50 = 0.005% sodium nitrite and 0.5% purple-fleshed
      sweet potato powder combination, PP25 = 0.25% purple-fleshed sweet potato powder,
      PP50 = 0.5% purple-fleshed sweet potato powder). The sausages were cooked to 74
      degrees C, stored at 4 degrees C for 6 wks, and used for chemical analysis,
      textural properties, and a sensory evaluation on 0, 2, 4 and 6 wks of storage,
      respectively. Similar CIE a* and b* values were determined in sausages from CON,
      SP25 and SP50 at the end of storage, and they were higher in CIE a* but lower in
      CIE b* than that of the PP25 and PP50 sausages. Significant differences were
      observed for brittleness and hardness when PFP was added to the sausages but were
      not confirmed after 4 wks of storage. The objective color score was influenced by
      adding PFP; however, the effect was not dose dependent. In overall acceptability,
      panelists favored the CON, SP25, SP50, and PP50 sausages but did not prefer PP25
      sausages at the end of storage. Therefore, adding PFP to cooked pork sausages
      improved color and texture properties and sensory characteristics, but further
      study is needed to determine the proper ratio of sodium nitrite and PFP. 

PMID- 25049700
TI  - Investments on Pro-poor Development Projects on Goats: Ensuring Success for
      Improved Livelihoods.
AB  - The elements that determine the success of development projects on goats and the
      prerequisites for ensuring this are discussed in the context of the bewildering
      diversity of goat genetic resources, production systems, multifunctionality, and
      opportunities for responding to constraints for productivity enhancement. Key
      determinants for the success of pro-poor projects are the imperatives of
      realistic project design, resolution of priorities and positive impacts to
      increase investments and spur agricultural growth, and appropriate policy.
      Throughout the developing world, there exist 97% of the total world population of
      921 million goats across all agro-ecological zones (AEZs), including 570 breeds
      and 64% share of the breeds. They occupy a very important biological and socio
      economic niche in farming systems making significant multifunctional
      contributions especially to food, nutrition and financial security, stability of
      farm households, and survival of the poor in the rural areas. Definitions are
      given of successful and failed projects. The analyses highlighted in successful
      projects the value of strong participatory efforts with farmers and climate
      change. Climate change effects on goats are inevitable and are mediated through
      heat stress, type of AEZ, water availability, quantity and quality of the
      available feed resources and type of production system. Within the prevailing
      production systems, improved integrated tree crops - ruminant systems are
      underestimated and are an important pathway to enhance C sequestration. Key
      development strategies and opportunities for research and development (R and D)
      are enormous, and include inter alia defining a policy framework, resolution of
      priority constraints using systems perspectives and community-based participatory
      activities, application of yield-enhancing technologies, intensification, scaling
      up, and impacts. The priority for development concerns the rainfed areas with
      large concentrations of ruminants in which goats, with a capacity to cope with
      heat tolerance, can be the entry point for development. Networks and networking
      are very important for the diffusion of information and can add value to R and D.
      Well formulated projects with clear priority setting and participatory R and D
      ensure success and the realisation of food security, improved livelihoods and
      self-reliance in the future. 

PMID- 25049699
TI  - Nutrition-induced Changes of Growth from Birth to First Calving and Its Impact on
      Mammary Development and First-lactation Milk Yield in Dairy Heifers: A Review.
AB  - This review focuses on the nutritional effects from birth until age at first
      calving on growth, mammary developmental changes, and first-lactation milk yield
      in heifer calves. The advancement in the genetic potential and the nutritional
      requirements of the animals has hastened the growth rate. Genetic selection for
      high milk yield has suggested higher growth capacity and hence increasing
      nutritional inputs are required. Rapid rearing by feeding high energy or high
      concentrate diets not only reduces the age of sexual maturity but also lowers the
      time period of attaining the age of first calving. However, high energy diets may
      cause undesirable fat deposition thereby affecting future milk yield potential.
      Discrepancies exist whether overfed or overweight heifers at puberty can
      influence the mammary development and future milk yield potential and
      performance. The data on post-pubertal nutritional management suggested that body
      weight at calving and post-pubertal growth rate is important in first lactation
      milk yield. There is a continuous research need for strategic feeding that
      accelerates growth of dairy heifers without reduction in subsequent production.
      Nutritional management from birth, across puberty and during pregnancy is
      critical for mammary growth and for producing a successful cow. This review will
      mostly highlight studies carried out on dairy breeds and possible available
      opportunities to manipulate nutritional status from birth until age at first
      calving. 

PMID- 25049702
TI  - Rapid Genotyping of MSTN Gene Polymorphism Using High-resolution Melting for
      Association Study in Rabbits.
AB  - The myostatin (MSTN) gene, as a negative regulator of skeletal muscle growth, has
      been proposed to be associated with production traits in farm animals. In the
      present study, a T/C variant at -125 bp (relative to ATG start codon) of
      5'regulatory region of rabbit MSTN was identified by direct sequencing. Two
      hundred and twenty two rabbits, which were randomly sampled from 3 breeds (Ira
      rabbits, Champagne rabbits and Tianfu black rabbits), were genotyped by high
      resolution melting (HRM). Comparing the genotyping results of 47 samples with
      direct sequencing, the HRM showed high sensitivity (0.96) and high specificity
      (0.98). In the three rabbit breeds, the allele C was the predominant allele. The
      polymorphic site showed high heterozygosity (He = 0.48) and high effective number
      of alleles (Ne = 1.91). The genetic diversity was reasonably informative
      (0.25<PIC<0.50). The association analysis showed that the genotype TC had
      significant effect on the 84-d-weight of rabbits compared with genotype CC (p =
      0.047). In contrast, the genotypes had no significant effect on other production
      traits. These results showed that HRM could be effectively used for genotyping
      analysis of MSTN gene. The T/C variant in 5'regulatory region of MSTN might be
      one of the candidate SNP loci affecting the trait of 84-d-weight. 

PMID- 25049701
TI  - Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in
      Hanwoo (Korean) Cattle.
AB  - Marbling (intramuscular fat) is an important trait that affects meat quality and
      is a casual factor determining the price of beef in the Korean beef market. It is
      a complex trait and has many biological pathways related to muscle and fat. There
      is a need to identify functional modules or genes related to marbling traits and
      investigate their relationships through a weighted gene co-expression network
      analysis based on the system level. Therefore, we investigated the co-expression
      relationships of genes related to the 'marbling score' trait and systemically
      analyzed the network topology in Hanwoo (Korean cattle). As a result, we
      determined 3 modules (gene groups) that showed statistically significant results
      for marbling score. In particular, one module (denoted as red) has a
      statistically significant result for marbling score (p = 0.008) and intramuscular
      fat (p = 0.02) and water capacity (p = 0.006). From functional enrichment and
      relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1,
      INHBA and NPPA) have a direct interaction relationship and share the biological
      functions related to fat or muscle, such as adipogenesis or muscle growth. This
      is the first gene network study with m.logissimus in Hanwoo to observe co
      expression patterns in divergent marbling phenotypes. It may provide insights
      into the functional mechanisms of the marbling trait. 

PMID- 25049703
TI  - A Study on BMPR-IB Genes of Bayanbulak Sheep.
AB  - The average twin lambing rate of Bayanbulak sheep is 2% to 3%. However, a flock
      of sheep with a close genetic relationship and an average of 2 to 3 lambs per
      birth has been found recently. To determine the major genes controlling the
      prolificacy of the flock in the present study, the flock was designated A while
      100 normal Bayanbulak sheep were randomly selected to comprise the control flock
      B. Ligase detection reaction method was applied to detect and analyze the 10
      mutational loci of the 3 candidate prolificacy genes including bone morphogenetic
      protein type I receptors, bone morphogenetic protein 15, and growth
      differentiation factor 9. The 10 mutational loci are as follows: FecB locus of
      the BMPR-IB gene; FecX(I) , FecX(B) , FecX(L) , FecX(H) , FecX(G) , and FecX(R)
      of the BMP15 gene; and G1, G8, and FecTT of the GDF9 gene. Two mutations
      including BMPR-IB/FecB and GDF9/G1 were found in Bayanbulak sheep. Independence
      test results of the two flocks demonstrate that the FecB locus has a significant
      effect on the lambing number of Bayanbulak sheep. However, the mutation frequency
      of the G1 locus in GDF9 is very low. Independence test results demonstrate that
      the GDF9 locus does not have a significant impact on the lambing performance of
      Bayanbulak sheep. Among the 10 detected loci, BMPR-IB/FecB is the major gene that
      influences the high lambing rate of Bayanbulak sheep. 

PMID- 25049704
TI  - Influence of rabbit sire genetic origin, season of birth and parity order on doe
      and litter performance in an organic production system.
AB  - The aim of this study was to compare both the performance of litters derived from
      two sire genetic origins (SGO), Vienna Blue (VB) and Burgundy Fawn (BF), along
      successive seasons of birth (SB; winter, spring, summer and autumn), and doe
      reproductive performance in an organic production system. A total of fifty-eight
      does consisting of a mixture of crosses of several medium-large size breeds at
      different parity order (P, 1 = nulliparous; 2 = primiparous; >=3 = multiparous)
      and twelve males (6 VB and 6 BF) were housed indoors at environmental conditions
      that followed seasonality. An extensive reproductive rhythm was used and kits
      were weaned at 46+/-6 d of age. Doe reproductive performance and the data of 105
      litters (55 from VB and 50 from BF SGO) were recorded throughout the SB. No
      statistically significant differences related to SGO effect were observed. As
      regards parity order, multiparous does showed higher live weights (LW) (p<0.05),
      total born (p<0.01), total born alive (p<0.05) per delivery, and litter weight of
      born alive (p<0.05), but lower milk output at 21st d than primiparous does
      (p<0.05). The extensive reproductive rhythm mainly increased litter performance
      at birth in multiparous does but was not sufficient to permit a complete recovery
      of body reserves lost during lactation. Autumn SB negatively affected doe LW
      variation between deliveries. The number of pups born and born alive per delivery
      (p<0.05) and litter size at 21 d of age and at weaning (p<0.01) were lower during
      hot SB. Due to the lower litter size of pups born in summer and autumn, their
      individual weight at 21st d of age and daily individual growth rate 0 to 21 d
      were higher than those of pups born in winter (p<0.001). Litter performance at
      21st d of age and individual pup pre-weaning growth rate were poorer for those
      born in spring than in other seasons due to the harmful effects of increased
      environmental temperatures. SB affected most of the performance traits of does
      and young rabbits reared under the organic farming system. The rabbits seemed
      better suited to organic rearing conditions during winter than in other seasons.
      The worst results overall were obtained in the spring SB, whereas the hot SB
      negatively affected both doe energy balance and prolificacy. In conclusion, the
      pups of the 2 SGO showed good pre-weaning performance and seemed suited to the
      organic rabbit production system. 

PMID- 25049705
TI  - Characterization of Cellulolytic and Xylanolytic Enzymes of Bacillus
      licheniformis JK7 Isolated from the Rumen of a Native Korean Goat.
AB  - A facultative bacterium producing cellulolytic and hemicellulolytic enzymes was
      isolated from the rumen of a native Korean goat. The bacterium was identified as
      a Bacillus licheniformis on the basis of biochemical and morphological
      characteristics and 16S rDNA sequences, and has been designated Bacillus
      licheniformis JK7. Endoglucanase activities were higher than those of beta
      glucosidase and xylanase at all temperatures. Xylanase had the lowest activity
      among the three enzymes examined. The optimum temperature for the enzymes of
      Bacillus licheniformis JK7 was 70 degrees C for endoglucanase (0.75 U/ml) and 50
      degrees C for beta-glucosidase and xylanase (0.63 U/ml, 0.44 U/ml, respectively).
      All three enzymes were stable at a temperature range of 20 to 50 degrees C. At 50
      degrees C, endoglucanse, beta-glucosidase, and xylanase had 90.29, 94.80, and
      88.69% residual activity, respectively. The optimal pH for the three enzymes was
      5.0, at which their activity was 1.46, 1.10, and 1.08 U/ml, respectively. The
      activity of all three enzymes was stable in the pH range of 3.0 to 6.0.
      Endoglucanase activity was increased 113% by K(+), while K(+), Zn(+), and tween
      20 enhanced beta-glucosidase activity. Xylanase showed considerable activity even
      in presence of selected chemical additives, with the exception of Mn(2+) and
      Cu(2+). The broad range of optimum temperatures (20 to 40 degrees C) and the
      stability under acidic pH (4 to 6) suggest that the cellulolytic enzymes of
      Bacillus licheniformis JK7 may be good candidates for use in the biofuel
      industry. 

PMID- 25049706
TI  - Mineral status in cattle fed rice straw and para grass combined with different
      levels of protein derived from cassava foliage.
AB  - Eight male cattle of the Local Yellow breed with an average live weight of 121 kg
      and an average age of 18 months were used to evaluate the effects of different
      levels of sun-dried cassava (Manihot esculenta) foliage supplementation on
      mineral metabolism in growing cattle fed rice straw and para grass as basal diet.
      Rice straw ad libitum and para grass (Brachiaria mutica) at 1% DM of BW comprised
      the basal diet. The study was arranged as a 4*4 double Latin square design, with
      cassava foliage contributing 0, 0.8, 1.6 or 2.4 g CP/kg BW. The cassava foliage
      intake was lower than the planned levels. DM consumption was significantly
      affected by cassava foliage supplementation, with the largest intake observed at
      the two highest levels of cassava foliage supplementation. Rice straw intake
      showed the opposite pattern, with lower intake at higher cassava foliage
      supplementation. No refusals occurred for para grass in any of the treatments.
      Ca, P, Mg, K, S and Mn intake increased significantly with increasing intake of
      cassava foliage, but Na intake was not affected by treatment. Faecal excretion of
      Ca, Mg, S and Mn increased significantly with increasing cassava foliage intake.
      There were no differences between P, K and Na excretion in faeces. There was a
      significant diet effect on Mg, S and Mn digestibility. Mg and Mn digestibility
      increased with increasing cassava foliage supplementation, while S digestibility
      decreased. Ca, P, K and Na digestibility was not affected by diet. There was a
      significant effect of treatment on P retention, with the highest value observed
      for supplementation with 1.6 g CP/kg BW cassava foliage. Ca and Mg showed similar
      trends, with the highest retention again for supplementation with 1.6 g CP/kg BW
      cassava foliage. There were weak but significant positive correlations between
      nitrogen retention and the macro minerals Ca, P and Mg. Furthermore, retention of
      all these minerals was positively correlated. Mineral losses in urine were not
      affected by dietary treatment with the exception of P excretion, which was
      affected by treatment. In conclusion, cassava foliage is a good Ca source which
      compensates for the low Ca content in rice straw and para grass, but P deficiency
      appears to be exaggerated in cattle with higher cassava intake. The results
      suggest that under these conditions growing cattle on a high cassava intake would
      benefit from P and S supplementation. 

PMID- 25049707
TI  - Long-term Bias of Internal Markers in Sheep and Goat Digestion Trials.
AB  - Two digestion trials, one with sheep and another with goats, were conducted to
      evaluate the long-term bias (LTB) of the indigestible dry matter (iDM),
      indigestible neutral detergent fiber (iNDF) and indigestible acid detergent fiber
      (iADF) internal markers. The study used eight Santa Ines castrated male sheep
      (average body weight of 16.6 kg) distributed in two 4*4 Latin squares and eight
      Saanen castrated male goats (average body weight of 22.6 kg) distributed in two
      4*4 Latin squares. The experiments were conducted simultaneously, and the animals
      were housed in 1.2 m(2) individual pens with wood-battened floors equipped with
      individual feeders and drinkers. The animals received isonitrogenous diets that
      were offered ad libitum and contained 14% crude protein and 70% sugar cane (with
      0, 0.75, 1.5 or 2.25% CaO, in natural matter percentage), corrected with 1% urea
      and 30% concentrate. The experiment consisted of four experimental periods of 14
      d each, with the feed, leftovers and feces sampled on the last four days of each
      period. The marker concentrations in the feed, leftovers and fecal samples were
      estimated by an in situ ruminal incubation procedure with a duration 240 h. The
      relationship between the intake and excretion of the markers was obtained by
      adjusting a simple linear regression model, independently from the treatment
      (diets) fixed effects and Latin squares. For both the sheep and goats, a complete
      recovery of the iDM and iNDF markers was observed (p>0.05), indicating the
      absence of LTB for these markers. However, the iADF was not completely recovered,
      exhibiting an LTB of -9.12% (p<0.05) in the sheep evaluation and -3.02% (p<0.05)
      in the goat evaluation. 

PMID- 25049708
TI  - Effects of soybean small peptides on rumen fermentation and on intestinal and
      total tract digestion of luxi yellow cattle.
AB  - Four Luxi beef cattle (400+/-10 kg) fitted with ruminal, duodenal and ileal
      cannulas were used in a 4*4 Latin square to assess the effects of soybean small
      peptide (SSP) infusion on rumen fermentation, diet digestion and flow of nutrient
      in the gastrointestinal tract. The ruminal infusion of SSP was 0 (control), 100,
      200 and 300 g/d. Ruminal SSP infusion linearly (p<0.01) and quadratically
      (p<0.01) increased microbial protein synthesis and rumen ammonia-N concentration.
      Concentrations of total volatile fatty acid were linearly increased (p = 0.029)
      by infusion SSP. Rumen samples were obtained for analysis of microbial ecology by
      real-time PCR. Populations of rumen Butyrivibrio fibrisolvens, Streptococcus
      bovis, Ciliate protozoa, Ruminococcus flavefaciens, and Prevotella ruminicola
      were expressed as a proportion of total Rumen bacterial 16S ribosomal
      deoxyribonucleic acid (rDNA). Butyrivibrio fibrisolvens populations which related
      to total bacterial 16S rDNA were increased (p<0.05), while Streptococcus bovis
      populations were linearly (p = 0.049) and quadratically (p = 0.020) decreased by
      infusion of SSP. Apparent rumen digestibility of DM and NDF were (Q, p<0.05; L,
      p<0.05) increased with infusion SSP. Total tract digestion of DM, OM and NDF were
      linearly (p<0.01) and quadratically (p<0.01) increased by infusing SSP. The flow
      of total amino acids (AA), essential amino acids (EAA) and individual amino acids
      were linearly (p<0.01) and quadratically (p<0.01) increased with infusion SSP.
      The digestibility of Lysine was quadratically (p = 0.033) increased and apparent
      degradability of Arginine was linearly (p = 0.032) and quadratically (p = 0.042)
      increased with infusion SSP. The results indicated that infusion SSP could
      improve nutrient digestion, ruminal fermentation and AA availability. 

PMID- 25049709
TI  - Effects of monensin on metabolism and production in dairy saanen goats in
      periparturient period.
AB  - This trial evaluated the effects of dietary supplementation with monensin sodium
      on dry matter intake, metabolic parameters and milk yield and milk composition of
      dairy Saanen goats in the periparturient period. Twelve Saanen pregnant dairy
      goats were assigned to a treatment and a control group. Saanen goats were fed
      monensin as its 10% sodium salt in the amount of 33 mg/kg of total dry matter
      intake during 30 d before parturition till d 42 in milk. Blood samples were
      collected from each goat at d 30, 15 and 7 before expected kidding time and also
      in d 1, 7, 13, 19, 21, 28, 35 and 42 postpartum. The serum concentrations of beta
      Hydroxybutyrate (BHBA), non-esterifed fatty acid (NEFA), calcium, magnesium,
      inorganic phosphorus, cholesterol, triglyceride, urea, total protein, albumin and
      glucose and aspartate aminotransferase (AST) activity were determined. The BHBA
      concentration significantly decreased in goats, which received monensin in
      comparison to controls in the postpartum period (p = 0.049). The concentration of
      sodium (Na) was significantly influenced by monensin treatment in the postpartum
      period (p = 0.048). In addition, the difference in dry matter intake was highly
      significant between the two groups during the pre-partum period. Controls had
      more dry matter intake (DMI) than treatment goats (p = 0.0001). Mean 3.5% fat
      corrected milk production was not influenced by monensin treatment. However, milk
      fat percentage was significantly decreased in monensin treated goats (p =
      0.0017). 

PMID- 25049710
TI  - Effects of Dietary Scutellaria baicalensis Extract on Growth, Feed Utilization
      and Challenge Test of Olive Flounder (Paralichthys olivaceus).
AB  - Effects of dietary Scutellaria baicalensis extract (SBE) on growth, feed
      utilization and challenge test of olive flounder (Paralichthys olivaceus) were
      determined. Six hundred thirty fish averaging 5.0 g were distributed into 18, 180
      L tanks. Six experimental diets were prepared in triplicate: SBE-0, SBE-0.5, SBE
      1, SBE-2, SBE-3 and SBE-5 diets containing SBE at the concentrations of 0, 0.5,
      1, 2, 3 and 5%, respectively. Fish were hand-fed to apparent satiation twice a
      day for 8 wks. At the end of 8-wk feeding trial, ten fish from each tank were
      infected by Edwardsiella tarda for challenge test. Survival and weight gain of
      fish were not affected by dietary concentrations of SBE. However, specific growth
      rate of fish fed the SBE-2 diet was higher than that of fish fed the SBE-0, SBE
      1, SBE-3 and SBE-5 diets. Neither feed efficiency nor serum chemical composition
      of fish was affected by dietary concentrations of SBE. The cumulative mortality
      of fish fed the SBE-0 diet was 100% at 96 h after E. tarda infection, but 77 to
      87% for fish fed the other diets. Dietary inclusion of 2% SBE appears to be
      recommendable to improve specific growth rate of fish and SBE had the potential
      to mitigate mortality of fish at E. tarda infection. 

PMID- 25049711
TI  - Chemical and physical predictors of the nutritive value of wheat in broiler
      diets.
AB  - The aim of this study was to establish relationships between chemical and
      physical parameters of wheat with performance and digestibilities of feed
      components in broiler chickens fed on wheat-based diets. Ninety-four wheat
      samples were selected for inclusion in four bird trials. Birds were housed in
      individual wire metabolism cages from 7 to 28 d and offered water and feed ad
      libitum. Dry matter intake (DMI), liveweight gain (LWG) and gain:feed were
      measured weekly. A balance collection was carried out from 14 to 21 d for
      determination of apparent metabolizable energy (AME), ME:gain, dry matter
      retention, oil and neutral detergent fibre (NDF) digestibility. At 28 d the birds
      were humanely killed, the contents of the jejunum removed for determination of in
      vivo viscosity and the contents of the ileum removed for determination of ileal
      dry matter, starch and protein digestibility. When wheat parameters were
      correlated with bird performance data, it was found that specific weight was not
      significantly (p>0.05) related to bird performance. Bird DMI, LWG and gain:feed
      were best correlated (p<0.05) with the rate of starch digestion, although the
      coefficients of correlation (r) were still low (0.246 to 0.523). A negative
      relationship (p<0.01) between AME and total (r = -0.432) and soluble (r = -0.304)
      non starch polysaccharide (NSP) was observed in this study. Thousand grain weight
      (TG) was positively correlated with DMI (r = 0.299), LWG (r = 0.343) and
      gain:feed (r = 0.371). When establishing multiple regression relationships,
      correlation coefficients greater than 0.8 were achieved for DMI, LWG, gain:feed
      and ileal crude protein digestibility. However, the economics involved in
      determining the parameters involved in the regressions make the process
      impractical. 

PMID- 25049712
TI  - Effects of Dietary Coptis Chinensis Herb Extract on Growth Performance, Nutrient
      Digestibility, Blood Characteristics and Meat Quality in Growing-finishing Pigs.
AB  - The effects of dietary Coptis chinensis herb extract (CHE) on growth performance,
      blood characteristics, nutrient digestibility and meat quality of growing
      finishing pigs were investigated in an 18-wk feeding trial. A total of 36
      Landrace*Yorkshire-Duroc pigs with an initial body weight of 20+/-1.0 kg were
      randomly assigned to 3 dietary treatments with 6 replications per treatment and 2
      pigs per pen. A maize-soybean meal-based diet was formulated as a control diet
      and other treatment diets were supplemented with 0.5, or 1 g CHE/kg,
      respectively. After the feeding period, meat samples were collected from those
      pigs that had reached the market BW. During the experimental periods, growth
      performance and apparent total tract digestibility of dry matter and nitrogen
      were unaffected (p>0.05) by the dietary supplementation of CHE. Plasma
      erythrocytes counts were increased (Linearly, p<0.05) in response to application
      of CHE at the end of the experiment. Moreover, pigs fed the CHE diets had better
      (p<0.05) meat color, pH and water holding capacity (WHC) than pigs fed the
      control diet. In conclusion, dietary supplementation with CHE could increase
      blood erythrocytes counts and improve meat quality in growing-finishing pigs but
      not improve growth performance. 

PMID- 25049713
TI  - Oligosaccharides affect performance and gut development of broiler chickens.
AB  - The effects of oligosaccharide supplementation on the growth performance, flock
      uniformity and GIT development of broiler chickens were investigated. Four diets,
      one negative control, one positive control supplemented with zinc-bacitracin, and
      two test diets supplemented with mannoligosaccharide (MOS) and
      fructooligosaccharide (FOS), were used for the experiment. Birds given MOS or FOS
      had improved body weight (BW) and feed efficiency (FCR), compared to those fed
      the negative control diet during the 35-d trial period. The effect on FCR became
      less apparent when the birds got older. FOS and MOS supplementation reduced the
      pancreas weight as a percentage of BW, with an effect similar to that of the
      antibiotic, at 35 d of age. Birds given MOS tended to have a heavier bursa (p =
      0.164) and lower spleen/bursa weight ratio (p = 0.102) at 35 d of age. MOS and Zn
      bacitracin showed a clear improvement on flock uniformity, compared to FOS. The
      mortality rate was not affected by FOS or MOS. 

PMID- 25049714
TI  - Effects of Residual Hypochlorite Ion on Methane Production during the Initial
      Anaerobic Digestion Stage of Pig Slurry.
AB  - The hypochlorite ion (OCl(-)) is a widely used disinfecting agent in pig rearing
      in Korea, but its residual effect on CH4 production from pig slurry is unclear.
      The objective of this study was to investigate the inhibition effects of residual
      OCl(-) on CH4 production during the initial anaerobic digestion stage of pig
      slurry. Three organic concentrations (9.9, 26.2 and 43.7 g/L) of volatile solids
      (VS) were tested with the addition of 52.3 mg/L OCl(-), ten times of the typical
      concentration used in Korea, or without OCl(-) (Control) in anaerobic batch
      culture. The culture was run under mesophilic (38 degrees C) conditions for 20 d.
      At the lowest organic concentration with OCl(-), the VS degradation was 10.3%
      lower (p<0.05) than Control, while at the higher organic concentration with OCl(
      ), it did not differ from Control. CH4 yields were higher in the control
      treatments than their OCl(-) counterpart cultures, and CH4 yields of Control and
      OCl(-) treatments at the organic concentrations of 9.9, 26.2 and 43.7 g/L
      differed in the probability level (p) of 0.31, 0.04, and 0.06, respectively.
      Additionally, CH4 concentration increased steeply and reached 70.0% within 4 d in
      the absence OCl(-), but a gradual increase up to 60.0% was observed in 6 d in the
      OCl(-) treated cultures. The Rm (the maximum specific CH4 production rate) and
      lambda (lag phase time) of 9.9 g/L with OCl(-) were 8.1 ml/d and 25.6 d, while
      the Rm was increased to 15.1 ml/d, and lambda was reduced to 11.4 d in PS-III
      (higher organic concentration) with OCl(-). The results suggest that a prolonged
      fermentation time was necessary for the methanogens to overcome the initial OCl(
      ) inhibitory effect, and an anaerobic reactor operated with high organic loadings
      was more advantageous to mitigate the inhibitory effect of residual hypochlorite
      ion. 

PMID- 25049715
TI  - Effect of Acacia karroo Supplementation on Growth, Ultimate pH, Colour and
      Cooking Losses of Meat from Indigenous Xhosa Lop-eared Goats.
AB  - The objective of the study was to determine the effect of Acacia karroo
      supplementation on growth, ultimate pH, colour and cooking losses of meat from
      indigenous Xhosa lop-eared goats. Eighteen castrated 4-month-old kids were used
      in the study until slaughter. The kids were subdivided in two treatment groups A.
      karroo supplemented (AK) and non-supplemented (NS). The supplemented goats were
      given 200 g per head per d of fresh A. karroo leaves. The kids were slaughtered
      on d 60 and sample cuttings for meat quality assessment were taken from the
      Longistimus dorsi muscle. The supplemented kids had higher (p<0.05) growth rates
      than the non-supplemented ones. The meat from the A. karroo supplemented goats
      had lower (p<0.05) ultimate pH and cooking loss than the meat from the non
      supplemented goats. Acacia karroo supplemented goats produced higher (p<0.05) b*
      (yellowness) value, but supplementation had no significant effect on L*
      (lightness) and a* (redness) of the meat. Therefore, A. karroo supplementation
      improved growth performance and the quality of meat from goats. 

PMID- 25049716
TI  - The Effect of Modified Atmosphere Packaging and Addition of Rosemary Extract,
      Sodium Acetate and Calcium Lactate Mixture on the Quality of Pre-cooked Hamburger
      Patties during Refrigerated Storage.
AB  - The effect of modified atmosphere packaging (MAP; 30% CO2+70% N2 or 100% N2) and
      an additive mixture (500 ppm rosemary extract, 3,000 ppm sodium acetate and 1,500
      ppm calcium lactate) on the quality of pre-cooked hamburger patties during
      storage at 5 degrees C for 14 d was evaluated. The addition of the additive
      mixture reduced aerobic and anaerobic bacteria counts in both 30% CO2-MAP (30%
      CO2+70% N2) and 100% N2-MAP (p<0.05). The 30% CO2-MAP was more effective to
      suppress the microbial growth than 100% N2-MAP, moreover the 30% CO2-MAP combined
      with additive mixture resulted in the lowest bacterial counts. The hamburger
      patties with additive mixture showed lower CIE L* and CIE a*, and higher CIE b*
      than those with no additive mixture. The 30% CO2-MAP tended to decrease the TBARS
      during storage regardless of the addition of additives. The use of 30% CO2-MAP in
      combination with additives mixture was effective for maintaining the quality and
      extending the shelf-life of pre-cooked hamburger patties. 

PMID- 25049717
TI  - Preliminary evaluation of slaughter value and carcass composition of indigenous
      sheep and goats from traditional production system in Tanzania.
AB  - The aim of the pilot study was to evaluate slaughter characteristics and carcass
      composition of indigenous long fat tailed sheep and Small East African goats
      purchased from the auction markets slaughtered at 1.5 to 2 yrs of age and 20 kg
      to 25 kg live weight. The animals were slaughtered according to halal standard
      procedures. The left half carcasses were jointed into eight wholesale joints, and
      dissected into muscles, fat and bone, which were weighed separately. Sheep had
      greater (p<0.05) slaughter BW (22.29 kg vs 20.50 kg) and empty BW (20.17 kg vs
      18.67 kg) than goats (p<0.05). Dressing percentages were lower (p<0.001) in sheep
      than goats when carcass weight was expressed as percentage of slaughter BW
      (42.31% and 47.15%) and empty BW (46.75% and 51.79%). Sheep carcasses had lower
      (p<0.001) proportion (66.18% vs 71.64%) of muscles and higher (p<0.001)
      proportion of fat (7.41% vs 3.44%) than goat carcasses. Sheep had proportionally
      lighter (p<0.001) shoulder (18.89% vs 22.68%) and heavier (p<0.05) proportion of
      chump (7.916% vs 6.76%) and main rib (8.12% vs 7.07%). Sheep had more (p<0.001)
      muscles in the leg (28.83% vs 27.08%) and main rib (7.62% vs 6.36%) than goats.
      Sheep had less (p<0.001) muscles (20.28% vs 23.56%) in shoulder joints when
      expressed as percentage of total muscle of carcasses. It is concluded that there
      are differences in sheep and goat both in terms of carcass and joint yields and
      composition. The present study also implies that there is need to consider
      setting different meat cuts and prices for these cuts when one takes into account
      the differences in muscle distribution within joints in sheep and goats. 

PMID- 25049718
TI  - Identification of Single Nucleotide Polymorphisms (SNPs) of the Bovine Growth
      Hormone (bGH) Gene Associated with Growth and Carcass Traits in Hanwoo.
AB  - The purpose of this study was to find any association of the bovine growth
      hormone (bGH) gene with growth and carcass quality traits in Korean native
      cattle, Hanwoo. Genomic DNA was extracted from 21 Hanwoo individuals, and the 47
      to 2,528 bp region of the bGH 2,856 bp (GenBank accession number M57764)
      including the promoter and the five exons was sequenced. A total of ten bGH SNPs
      were confirmed, including four (253 C>T, 303 C>T, 502 C>T, and 559 G>A) in the
      promoter, one (679 C>T) in exon 1, one (1,692 T>C) in intron 3, and four (2141
      C>G, 2258 C>T, 2277 C>T, and 2291 A>C) in exon 5. The ten bGH SNPs were genotyped
      for a sample of 242 Hanwoo steers and association tests were performed to find
      any significant SNP that was correlated with growth and carcass quality. Of the
      SNPs, the 303 C>T SNP in the promoter region was significantly associated with 6
      month-old weight, the 559 G>A SNP with longissimus dorsi muscle area, the 2141
      C>G SNP in exon 5 with daily weight gain, and the 2258 C>T SNP with daily weight
      gain and carcass weight (p<0.05). The significant SNPs need to be verified in
      other Hanwoo populations before considering implementation of marker-assisted
      selection for genetic improvement of growth and carcass quality in Hanwoo. 

PMID- 25049719
TI  - Effect of FTO Expression and Polymorphism on Fat Deposition in Suzhong Pigs.
AB  - Fat mass and obesity associated gene (FTO) plays an important role in appetite
      control and energy consumption in human and mice. In order to examine FTO
      expression influence on fat deposition in Suzhong pigs, FTO mRNA expression was
      detected in 16 tissues by RT-PCR, FTO protein expression was detected in 5
      tissues by western blot, and association of FTO polymorphism with meat quality
      traits was analyzed in Suzhong populations with 714 records. RT-PCR results
      revealed that FTO mRNA was expressed in all sixteen tissues with significant
      differences (p<0.05), expression in backfat was significantly higher than that of
      any other tissue (p<0.05), and expression in longissimus dorsi muscle had the
      second highest significance level (p<0.05). Western blot results demonstrated
      that FTO protein was highly expressed in backfat and longissimus dorsi muscle.
      Furthermore, FTO mRNA and protein expression in tissues of high-fat pigs was
      significantly higher than that of low-fat pigs (p<0.05), suggesting FTO
      expression had advantageous effects on fat deposition. FTO polymorphism results
      evidenced that at A227G locus, G allele seemed to have advantageous effects on
      fat deposition, indicating it could be a significant candidate gene for improving
      pork quality in Suzhong pigs. 

PMID- 25049720
TI  - The Possibility of TBC1D21 as a Candidate Gene for Teat Numbers in Pigs.
AB  - Based on a quantitative traits locus (QTL) study using a F2 intercross between
      Landrace and Korean native pigs, a significant QTL affecting teat numbers in SSC7
      was identified. The strong positional candidate gene, TBC1D21, was selected due
      to its biological function for epithelial mesenchymal cell development. Sequence
      analysis revealed six single nucleotide polymorphisms (SNPs) in the TBC1D21 gene.
      Among these, two SNP markers, one silent mutation (SNP01) for g.13,050A>G and one
      missense mutation (SNP04) for c.829A>T (S277C), were genotyped and they showed
      significant associations with teat number traits (p value = 6.38E-05 for SNP01
      and p value = 1.06E-07 for SNP04 with total teat numbers). Further functional
      validation of these SNPs could give valuable information for understanding the
      teat number variation in pigs. 

PMID- 25049721
TI  - Association of polymorphism harbored by tumor necrosis factor alpha gene and sex
      of calf with lactation performance in cattle.
AB  - In a majority of mammals, male infants have heavier body mass and grow faster
      than female infants. Accordingly, male offspring nursing requires a much greater
      maternal energy contribution to lactation. It is possible that the maternal-fetal
      immunoendocrine dialog plays an important role in female preparation for
      lactation during pregnancy. Immune system genes are an integral part of gene
      regulatory networks in lactation and tumor necrosis factor alpha (TNFalpha) is a
      proinflammatory cytokine that also plays an important role in normal mammary
      gland development. The aim of this study was to evaluate the influence of the sex
      of calf and/or the -824A/G polymorphism in the promoter region of TNFalpha gene
      on milk performance traits in Black Pied cattle over the course of lactation. We
      also studied the allele frequency differences of -824A/G variants across several
      cattle breeds, which were bred in different climatic conditions. The G allele
      frequency decreased gradually over the course of lactation events in the Black
      Pied dairy cattle because of a higher culling rate of cows with the G/G genotype
      (p<0.001). In contrast to the genotypes A/A and A/G, cows with G/G genotype
      showed significant variability of milk and milk fat yield subject to sex of
      delivered calf. Milk yield and milk fat yield were significantly higher in the
      case of birth of a bull calf than with a heifer calf (p<0.03). The G allele
      frequency varies from 48% to 58% in Grey Ukrainian and Black Pied cattle to 77%
      in aboriginal Yakut cattle. Our results suggest that the TNFalpha -824A/G gene
      polymorphism may have an influence on the reproductive efforts of cows over the
      course of lactation events depending on the sex of progeny. Allocation of
      resources according to sex of the calf allows optimizing the energy cost of
      lactation. This may be a probable reason for high G allele frequency in Yakut
      cattle breeding in extreme environmental conditions. Similarly, the dramatic fall
      in milk production after birth of a heifer calf increases the probability of
      culling for the cows with the G/G genotype in animal husbandry. 

PMID- 25049722
TI  - Effect of carcass traits on carcass prices of holstein steers in Korea.
AB  - The present study investigated the contribution of carcass traits on carcass
      prices of Holstein steers in Korea. Phenotypic data consisted of 76,814
      slaughtered Holsteins (1 to 6 yrs) from all over Korea. The means for live body
      weight at slaughter (BWT), chilled carcass weight (CWT), dressing percentage
      (DP), quantity grade index (QGI), eye muscle area (EMA), backfat thickness (BF)
      and marbling score (MS), carcass unit price (CUP), and carcass sell prices (CSP)
      were 729.0 kg, 414.2 kg, 56.79%, 64.42, 75.26 cm(2), 5.77 mm, 1.98, 8,952.80
      Korean won/kg and 3,722.80 Thousand Korean won/head. Least squares means were
      significantly different by various age groups, season of slaughter, marbling
      scores and yield grades. Pearson's correlation coefficients of CUP with carcass
      traits ranged from 0.12 to 0.62. Besides, the relationships of carcass traits
      with CSP were relatively stronger than those with CUP. The multiple regression
      models for CUP and CSP with carcass traits accounted 39 to 63% of the total
      variation, respectively. Marbling score had maximum economic effects (partial
      coefficients) on both prices. In addition, the highest standardized partial
      coefficients (relative economic weights) for CUP and CSP were calculated to be on
      MS and CWT by 0.608 and 0.520, respectively. Path analyses showed that MS (0.376)
      and CWT (0.336) had maximum total effects on CUP and CSP, respectively; whereas
      BF contributed negatively. Further sub-group (age and season of slaughter)
      analyses also confirmed the overall outcomes. However, the relative economic
      weights and total path contributions also varied among the animal sub-groups.
      This study suggested the significant influences of carcass traits on carcass
      prices; especially MS and CWT were found to govern the carcass prices of Holstein
      steers in Korea. 

PMID- 25049723
TI  - Effects of IFN-gamma on IL-18 Expression in Pregnant Rats and Pregnancy Outcomes.
AB  - The present study focused on establishing the effects of interferon-gamma (IFN
      gamma) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in
      pregnant rats. Pregnant rats at the post-implantation stage were randomized into
      control, low IFN-gamma (L-IFN-gamma) and high IFN-gamma groups (H-IFN-gamma) that
      received normal saline, 100 IU/g of IFN-gamma and 500 IU/g of IFN-gamma vaginal
      muscular injection, respectively. The effects of IFN-gamma on IL-18 expression
      and pregnancy outcomes were assessed systematically using several methods,
      including immunohistochemistry streptavidin-perosidase (SP), image pattern
      analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC)
      count, microscopy and visual observation. IL-18 was detected in the uteri of all
      pregnant rats, and mainly distributed in the endometrium, decidual cells,
      vascular endothelium and myometrium. Immunohistochemistry and image pattern
      analyses revealed significantly lower IL-18 expression in the H-IFN-gamma group
      compared to the L-IFN-gamma and control groups (p<0.01), indicating that high
      doses of IFN-gamma induce downregulation of IL-18 in the uterus of pregnant rats.
      ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN
      gamma group was lower than that of the L-IFN-gamma group (p<0.05), and
      significantly reduced compared to the control group (p<0.01). Moreover, the
      number of peripheral leukocytes in the H-IFN-gamma group was significantly higher
      than those in the control and L-IFN-gamma groups (p<0.01). Morphology analysis
      showed no evident differences between the L-IFN-gamma and control groups.
      However, for the H-IFN-gamma group, uterine mucosa bleeding, necrosis and
      excoriation were observed using microscopy. Visual observation revealed marroon,
      swelling, crassitude and no embryo in the uterus, which are obvious indicators of
      abortion. These results indicate that IFN-gamma plays a regulatory role in IL-18
      expression in the uterus and peripheral blood of pregnant rats at the post
      implantation stage. Moreover, high levels (500 IU/g) of IFN-gamma influence
      normal pregnancy at the early stages in rats by downregulating IL-18 expression
      in the uterus and peripheral blood and increasing the number of peripheral
      leukocytes, consequently triggering termination of pregnancy. 

PMID- 25049724
TI  - Neutrophil functions and cytokines expression profile in buffaloes with impending
      postpartum reproductive disorders.
AB  - The study was conducted to correlate the periparturient immune status in terms of
      neutrophil functions and cytokine expression in peripheral blood mononuclear cell
      culture with impending postpartum reproductive disorders in buffaloes. Forty
      pregnant buffaloes were observed for occurrence of postpartum reproductive
      disorders (PRD), i.e., metritis, endometritis and delayed uterine involution
      etc., during one week prepartum to four weeks postpartum period. A representative
      number (n = 6) of buffaloes that did not develop any PRD were included in group I
      (healthy, control), while the animals which experienced PRD were assigned into
      group II (PRD, n = 8). The blood samples were collected at weekly interval from
      one week prepartum to four weeks postpartum period considering the day of calving
      as 'd 0'. Differential leucocytes counts, superoxide and hydrogen peroxide
      production activity in isolated neutrophils and the mRNA expression profile of
      cytokines i.e., IL-2, IL-4 and IFN-gamma in PBMC culture were studied in all the
      samples. A higher total leucocytes, neutrophil and band cells count along with
      impaired neutrophil functions i.e., lowered level of production of superoxide and
      hydrogen peroxide before parturition and during early postpartum period were
      observed in buffaloes developing PRD. Further, a lower expression of IL-2, IFN
      gamma and IL-4 mRNA in PBMC culture was observed at calving in buffaloes that
      subsequently developed PRD at later postpartum. Thus, suppression in neutrophil
      function and cytokine expression at prepartum to early postpartum period
      predisposes the buffaloes to develop postpartum reproductive disorders. Hence,
      monitoring of neutrophils function and cytokine expression profile would be
      effective to predict certain reproductive disorders at late pregnancy or
      immediately after parturition in buffaloes. In future, this may be a novel
      approach for determining suitable management and therapeutic decisions for
      prevention of commonly occurring reproductive disorders in farm animals. 

PMID- 25049725
TI  - Production of Citrate by Anaerobic Fungi in the Presence of Co-culture
      Methanogens as Revealed by (1)H NMR Spectrometry.
AB  - The metabolomic profile of the anaerobic fungus Piromyces sp. F1, isolated from
      the rumen of goats, and how this is affected by the presence of naturally
      associated methanogens, was analyzed by nuclear magnetic resonance spectroscopy.
      The major metabolites in the fungal monoculture were formate, lactate, ethanol,
      acetate, succinate, sugars/amino acids and alpha-ketoglutarate, whereas the co
      cultures of anaerobic fungi and associated methanogens produced citrate. This is
      the first report of citrate as a major metabolite of anaerobic fungi. Univariate
      analysis showed that the mean values of formate, lactate, ethanol, citrate,
      succinate and acetate in co-cultures were significantly higher than those in the
      fungal monoculture, while the mean values of glucose and alpha-ketoglutarate were
      significantly reduced in co-cultures. Unsupervised principal components analysis
      revealed separation of metabolite profiles of the fungal mono-culture and co
      cultures. In conclusion, the novel finding of citrate as one of the major
      metabolites of anaerobic fungi associated with methanogens may suggest a new yet
      to be identified pathway exists in co-culture. Anaerobic fungal metabolism was
      shifted by associated methanogens, indicating that anaerobic fungi are important
      providers of substrates for methanogens in the rumen and thus play a key role in
      ruminal methanogenesis. 

PMID- 25049726
TI  - Using Plant Source as a Buffering Agent to Manipulating Rumen Fermentation in an
      In vitro Gas Production System.
AB  - The objective of this study was to investigate the effect of banana flower powder
      (BAFLOP) supplementation on gas production kinetics and rumen fermentation
      efficiency in in vitro incubation with different ratios of roughage to
      concentrate in swamp buffalo and cattle rumen fluid. Two male, rumen fistulated
      dairy steers and swamp buffaloes were used as rumen fluid donors. The treatments
      were arranged according to a 2*2*3 factorial arrangement in a Completely
      randomized design by using two ratios of roughage to concentrate (R:C; 75:25 and
      25:75) and 3 levels of BAFLOP supplementation (0, 2 and 4% of dietary substrate)
      into two different kinds of rumen fluid (beef cattle and swamp buffalo). Under
      this investigation, the results revealed that the rumen ecology was affected by
      R:C ratio. The pH declined as a result of using high concentrate ratio; however,
      supplementation of BAFLOP could buffer the pH which led to an improvement of
      ruminal efficiency. BAFLOP supplementation affected acetic acid (C2) when the
      proportion of concentrate was increased. However, there were no effect on total
      volatile fatty acid (TVFA) and butyric acid (C4) by BAFLOP supplementation. The
      microbial community was affected by BAFLOP supplementation, especially the
      bacterial population. As revealed by real-time PCR, the populations of F.
      succinogenes and R. albus were reduced by the high concentrate treatments while
      that of R. flavafaciens were increased. The populations of three dominant
      cellulolytic bacteria were enhanced by BAFLOP supplementation, especially on high
      concentrate diet. BAFLOP supplementation did not influence the ammonia nitrogen
      (NH3-N) concentration, while R:C did. In addition, the in vitro digestibility was
      improved by either R:C or BAFLOP supplementation. The BAFLOP supplementation
      showed an effect on gas production kinetics, except for the gas production rate
      constant for the insoluble fraction (c), while treatments with high concentrate
      ratio resulted in the highest values. In addition, BAFLOP tended to increase gas
      production. Based on this study, it could be concluded that R:C had an effect on
      rumen ecology both in buffalo and cattle rumen fluid and hence, BAFLOP could be
      used as a rumen buffering agent for enhancing rumen ecology fed on high
      concentrate diet. It is recommended that level of BAFLOP supplementation should
      be at 2 to 4% of total dry matter of substrate. However, in vivo trials should be
      subsequently conducted to investigate the effect of BAFLOP in high concentrate
      diets on rumen ecology as well as ruminant production. 

PMID- 25049727
TI  - Effects of feeding increasing proportions of corn grain on concentration of
      lipopolysaccharide in the rumen fluid and the subsequent alterations in immune
      responses in goats.
AB  - This study was conducted to investigate the effects of feeding increasing
      proportions of corn grain on concentration of lipopolysaccharide (LPS) in the
      rumen fluid and the subsequent alterations in immune responses as reflected by
      plasma concentrations of serum amyloid A (SAA) and haptoglobin (Hp) in goats.
      Nine goats were assigned to three diets (0%, 25%, and 50% corn grain) in a 3 *3
      Latin square experimental design. The results showed that as the proportion of
      dietary corn increased, the ruminal pH decreased (p< 0.001), and the
      concentrations of propionate (p<0.001), butyrate (p<0.001), lactic acid (p =
      0.013) and total volatile fatty acid (p = 0.031) elevated and the ruminal LPS
      level increased (p<0.001). As the proportion of dietary corn increased, the
      concentration of SAA increased (p = 0.013). LPS was detectable in the blood of
      individual goats fed 25% and 50% corn. A real-time PCR analysis showed that the
      copy number of phylum Bacteroidetes (p<0.001) was reduced (4.61*10(9)copies/mL to
      1.48*10(9)copies/mL) by the increasing dietary corn, and a correlation analysis
      revealed a significant negative correlation between the number of Bacteroidetes
      and rumen LPS levels. Collectively, these results indicated that feeding goats
      high proportions (50%) of corn grain decreased the ruminal pH, increased LPS in
      the rumen fluid and tended to stimulate an inflammatory response. 

PMID- 25049728
TI  - Influence of Dietary Supplementation of Condensed Tannins through Leaf Meal
      Mixture on Intake, Nutrient Utilization and Performance of Haemonchus contortus
      Infected Sheep.
AB  - The study assessed the effect of dietary supplementation of leaf meal mixture
      (LMM) containing condensed tannins (CT) on feed intake, nutrient utilization and
      performance of sheep infected with Haemonchus contortus. Eighteen adult sheep of
      similar age and body weight (25.03+/-1.52) were included in this study and out of
      these, 12 sheep were infected with single dose of infective third stage larvae of
      H. contortus at 2,000 larvae per sheep. The experimental sheep were allocated in
      three different groups' i.e. negative control (NC; no infection), control (C; H.
      contortus infected) and treatment (T; H. contortus infected+CT at 1.5% of the DM
      through LMM) and the experiment was conducted for a period of 90 d. The intake of
      dry matter (DM), organic matter (OM) and digestibility of DM, OM, neutral
      detergent fibre (NDF) and acid detergent fibre (ADF) were comparable among three
      animal groups. However, digestibility of crude protein (CP) and ether extract
      (EE) were significantly (p<0.05) higher in NC group as compared to both C and T
      groups. Nitrogen (N) retention (g/d or % of N intake) was significantly (p =
      0.038) lower in C group as compared to T and NC groups. Daily intake (g/kg
      W(0.75)) of digestible crude protein (DCP), digestible organic matter (DOM) and
      total digestible nutrient (TDN) did not differ significantly (p<0.05) in the
      three groups. Haemoglobin (Hb) and packed cell volume (PCV) were significantly
      (p<0.001) higher in treatment group as compared to control. The level of Hb and
      PCV reduced (p<0.001) after 30 days of experimental feeding. CT significantly
      (p<0.001) reduced serum urea in T group as compared to NC and C groups. Serum
      proteins differed significantly (p<0.01) among the three groups. The activity of
      serum enzymes AST, ALT, ALP and LDH were also statistically non significant
      (p<0.05) among treatments. The weight of abomasal lymph nodes (ALN) in T group
      was higher (p<0.05) than in C group. Treatment group had lower (p<0.05) total
      worms and fecal egg count compared to control group. It may be concluded that
      dietary supplementation of CT through LMM significantly improved the N retention,
      and inhibited the different developmental stages of Haemonchus contortus in
      experimental sheep. 

PMID- 25049729
TI  - Effects of Methylcellulose on Fibrolytic Bacterial Detachment and In vitro
      Degradation of Rice Straw.
AB  - Two in vitro experiments were conducted to evaluate the effect of methylcellulose
      (MC) on i) bacterial detachment from rice straw as well as ii) inhibition of
      bacterial attachment and fiber digestibility. To evaluate the effect of MC on
      fibrolytic bacterial detachment (Exp 1), in vitro bacterial cultures with 0.1%
      (w/v) MC solution were compared with cultures without MC after 8 h incubation.
      The effect of MC on inhibition of bacterial attachment was determined by
      comparing with real-time PCR the populations of F. succinogenes, R. flavefaciens
      and R. albus established on rice straw pre-treated with 0.1% MC with those on
      untreated straw after incubation for 0, 6 and 12 h (Exp 2). The major fibrolytic
      bacterial attachment on rice straw showed significantly lower populations with
      either the addition of MC to the culture or pre-treated rice straw compared to
      controls (p<0.05). Also, the digestibility of rice straw with MC was
      significantly lower compared with control (p<0.05). The F. succinogenes
      population did not show detachment from rice straw, but showed an inhibition of
      attachment and proliferation on rice straw in accordance with a decrease of fiber
      digestion. The detachments of Ruminococcus species co-existed preventing the
      proliferations with subsequent reduction of fiber degradation by MC during the
      incubation. Their detachments were induced from stable colonization as well as
      the initial adhesion on rice straw by MC in in vitro ruminal fermentation.
      Furthermore, the detachment of R. albus was more sensitive to MC than was R.
      flavefaciens. These results showed the certain evidence that attachment of major
      fibrolytic bacteria had an effect on fiber digestion in the rumen, and each of
      fibrolytic bacteria, F. succinogenes, R. flavefaciens and R. albus had a specific
      mechanism of attachment and detachment to fiber. 

PMID- 25049730
TI  - Validation of prediction equations to estimate the energy values of feedstuffs
      for broilers: performance and carcass yield.
AB  - The objective was to evaluate the use of prediction equations based on the
      chemical composition of feedstuffs to estimate the values of apparent
      metabolisable energy corrected for nitrogen balance (AMEn) of corn and soybean
      meal for broilers. For performance and carcass characteristics, 1,200 one-d-old
      birds (male and female) were allotted to a completely randomised factorial 2*8
      (two genders and eight experimental diets) with three replicates of each sex with
      25 birds. In the metabolism trial, 240 eight-d-old birds were distributed in the
      same design, but with a split plot in time (age of evaluation) with five, four
      and three birds per plot, respectively, in stages 8 to 21, 22 to 35, and 36 to 42
      d of age. The treatments consisted of the use of six equations systems to predict
      the AMEn content of feedstuffs, tables of food composition and AMEn values
      obtained by in vivo assay, totalling eight treatments. Means were compared by
      Scott-Knott test at 5% probability and a confidence interval of 95% was used to
      check the fit of the energy values of the diets to the requirements of the birds.
      As a result of this study, the use of prediction equations resulted in better
      adjustment to the broiler requirements, resulting in better performance and
      carcass characteristics compared to the use of tables, however, the use of energy
      values of feedstuffs obtained by in vivo assay is still the most effective. The
      best equations were: AMEn = 4,021.8-227.55 Ash (for corn) combined with AMEn = 
      822.33+69.54 CP-45.26 ADF+90.81 EE (for soybean meal); AMEn = 36.21 CP+85.44
      EE+37.26 NFE (nitrogen-free extract) (for corn) combined with AMEn = 37.5
      CP+46.39 EE+14.9 NFE (for soybean); and AMEn = 4,164.187+51.006 EE-197.663 Ash
      35.689 CF-20.593 NDF (for corn and soybean meal). 

PMID- 25049731
TI  - Effects of chitosan on body weight gain, growth hormone and intestinal morphology
      in weaned pigs.
AB  - The study was conducted to determine the effects of chitosan on the
      concentrations of GH and IGF-I in serum and small intestinal morphological
      structure of piglets, in order to evaluate the regulating action of chitosan on
      weaned pig growth through endocrine and intestinal morphological approaches. A
      total of 180 weaned pigs (35 d of age; 11.56+/-1.61 kg of body weight) were
      selected and assigned randomly to 5 dietary treatments, including 1 basal diet
      (control) and 4 diets with chitosan supplementation (100, 500, 1,000 and 2,000
      mg/kg, respectively). Each treatment contained six replicate pens with six pigs
      per pen. The experiment lasted for 28 d. The results showed that the average body
      weight gain (BWG) of pigs was improved quadratically by dietary chitosan during
      the former 14 d and the later 14 d after weaned (p<0.05). Furthermore, dietary
      supplementation of chitosan tended to quadratically increase the concentration of
      serum GH on d 14 (p = 0.082) and 28 (p = 0.087). Diets supplemented with
      increasing levels of chitosan increased quadratically the villus height of
      jejunum and ileum on d 14 (p = 0.089, p<0.01) and 28 (p = 0.074, p<0.01),
      meanwhile, chitosan increased quadratically the ratio of villus height to crypt
      depth in duodenum, jejunum and ileum on d 14 (p<0.05, p = 0.055, p<0.01) and 28
      (p<0.01, p<0.01, p<0.01), however, it decreased quadratically crypt depth in
      ileum on d 14 (p<0.05) and that in duodenum, jejunum and ileum on d 28 (p<0.01,
      p<0.05, p<0.05). In conclusion, these results indicated that chitosan could
      quadratically improve growth in weaned pigs, and the underlying mechanism may due
      to the increase of the serum GH concentration and improvement of the small
      intestines morphological structure. 

PMID- 25049732
TI  - Effects of Cooking End-point Temperature and Muscle Part on Sensory 'Hardness'
      and 'Chewiness' Assessed Using Scales Presented in ISO11036:1994.
AB  - Texture and 'tenderness' in particular, is an important sensory characteristic
      for consumers' satisfaction of beef. Objective and detailed sensory measurements
      of beef texture have been needed for the evaluation and management of beef
      quality. This study aimed to apply the sensory scales defined in ISO11036:1994 to
      evaluate the texture of beef. Longissimus and Semitendinosus muscles of three
      Holstein steers cooked to end-point temperatures of 60 degrees C and 72 degrees C
      were subjected to sensory analyses by a sensory panel with expertise regarding
      the ISO11036 scales. For the sensory analysis, standard scales of 'chewiness' (9
      points) and 'hardness' (7-points) were presented to the sensory panel with
      reference materials defined in ISO11036. As a result, both 'chewiness' and
      'hardness' assessed according to the ISO11036 scales increased by increasing the
      cooking end-point temperature, and were different between Longissimus and
      Semitendinosus muscles. The sensory results were in good agreement with
      instrumental texture measurements. However, both texture ratings in this study
      were in a narrower range than the full ISO scales. For beef texture, ISO11036
      scales for 'chewiness' and 'hardness' are useful for basic studies, but some
      alterations are needed for practical evaluation of muscle foods. 

PMID- 25049733
TI  - Influence of Municipal Abattoir Conditions and Animal-related Factors on
      Avoidance-related Behaviour, Bleeding Times at Slaughter and the Quality of Lamb
      Meat.
AB  - The objective of this study was to determine the effect of municipal abattoir
      conditions and animal factors on avoidance-related behaviour (AB) of sheep at
      slaughter, bleeding times (BT) and mutton quality. The behaviour of 66 castrates
      and 19 ewes of different age categories was observed at three stages of
      slaughter. Higher behaviour scores indicated higher levels of AB. Time intervals
      between the start of blood flow and the time the flow changed from a constant
      stream into drips were recorded as BT. Thirty two meat samples were obtained to
      measure quality variables. These were colour (L*, a* and b*), pH24, temperature,
      cooking loss (CL) and tenderness. Correlations were determined between BT and
      meat quality variables. Animal behaviour at slaughter differed with breed, gender
      and age group. Avoidance behaviour was higher in the Dorper breed than in both
      the Merino breed and their crosses. It was also higher in younger (<10 months)
      lambs than in older sheep. Castrates were more aggressive or in panic than ewes.
      Castrates had longer (72.6+/-0.53 s) BT than the ewes (63.6+/-2.82 s). Ewes had
      higher CL (39.8+/-1.04%) values than castrates (35.1+/-0.95%). Meat from
      castrates was tougher (32.6+/-1.95 N) than the meat from ewes (24.3+/-1.16 N).
      There were no significant correlations obtained between BT and meat quality
      variables. It can therefore be concluded that abattoir conditions, breed, age and
      gender had an effect on AB at slaughter. Gender had an effect on BT and mutton
      quality. 

PMID- 25049734
TI  - Effect of hybridization on carcass traits and meat quality of erlang mountainous
      chickens.
AB  - Native chickens hold a significant share of the market in China. In response to
      the huge demand from the market, the productivity of Chinese native chickens
      needs to be improved. Cross breeding is an effective method to increase
      productivity, although it might affect meat quality. In this study, two pure
      lines (SD02 and SD03) of Erlang mountainous chickens were hybridized with a
      yellow feather and faster growing line (SD01). The effect of hybridization on
      carcass and meat quality (physiochemical and textural traits) was measured in the
      F1 population at d 91 of age. The hybrids exhibited higher body weight and
      dressed weight, and amount of semi-eviscerated, eviscerated, breast muscle and
      abdominal fat (p<0.05). Abdominal fat yield also increased (p<0.05) compared to
      the offspring of the two pure-lines. Meanwhile, there was no significant
      difference in meat quality traits except for the myofiber diameter and density
      and the shear force of the breast muscle. Overall, the offspring of cross-lines
      were similar to pure lines in meat color, pH value, inosinic acid, crude protein,
      crude fat, dry matter, moisture content and amino acid composition in the breast
      muscle. These results suggest that productivity can be improved via cross
      breeding while maintaining meat quality of the Erlang mountainous chicken. 

PMID- 25049735
TI  - The effect of age at first calving and calving interval on productive life and
      lifetime profit in korean holsteins.
AB  - This study was performed to estimate the effect of age at first calving and first
      two calving intervals on productive life and life time profit in Korean
      Holsteins. Reproduction data of Korean Holsteins born from 1998 to 2004 and
      lactation data from 276,573 cows with birth and last dry date that calved between
      2000 and 2010 were used for the analysis. Lifetime profit increased with the days
      of life span. Regression of Life Span on Lifetime profit indicated that there was
      an increase of 3,800 Won (approximately $3.45) of lifetime profit per day
      increase in life span. This is evidence that care of each cow is necessary to
      improve net return and important for farms maintaining profitable cows. The
      estimates of heritability of age at first calving, first two calving intervals,
      days in milk for lifetime, lifespan, milk income and lifetime profit were 0.111,
      0.088, 0.142, 0.140, 0.143, 0.123, and 0.102, respectively. The low
      heritabilities indicated that the productive life and economical traits include
      reproductive and productive characteristics. Age at first calving and interval
      between first and second calving had negative genetic correlation with lifetime
      profit (-0.080 and -0.265, respectively). Reducing age at first calving and first
      calving interval had a positive effect on lifetime profit. Lifetime profit
      increased to approximately 2,600,000 (2,363.6) from 800,000 Won ($727.3) when age
      at first calving decreased to (22.3 month) from (32.8 month). Results suggested
      that reproductive traits such as age at first calving and calving interval might
      affect various economical traits and consequently influenced productive life and
      profitability of cows. In conclusion, regard of the age at first calving must be
      taken with the optimum age at first calving for maximum lifetime profit being
      22.5 to 23.5 months. Moreover, considering the negative genetic correlation of
      first calving interval with lifetime profit, it should be reduced against the
      present trend of increase. 

PMID- 25049736
TI  - Association of Tyrosinase (TYR) and Tyrosinase-related Protein 1 (TYRP1) with
      Melanic Plumage Color in Korean Quails (Coturnix coturnix).
AB  - TYR (Tyrosinase) and TYRP1 (Tyrosinase-related protein 1) play crucial roles in
      determining the coat color of birds. In this paper, we aimed to characterize the
      relationship of TYR and TYRP1 genes with plumage colors in Korean quails. The
      SNPs were searched by cDNA sequencing and PCR-SSCP in three plumage color Korean
      quails (maroon, white and black plumage). Two SNPs (367T->C and 1153C->T) were
      found in the coding region of TYRP1 gene, but had no significant association with
      plumage phenotype in Korean quails. The expression of TYR was higher in black
      plumage quails than that in maroon plumage quails. In contrast, the expression of
      TYRP1 was lower in black plumage quails than that in maroon plumage quails. This
      study suggested that the melanic plumage color in Korean quails may be associated
      with either increased production of TYR or decreased production of TYRP1. 

PMID- 25049737
TI  - Genome-wide Association Study of Chicken Plumage Pigmentation.
AB  - To increase plumage color uniformity and understand the genetic background of
      Korean chickens, we performed a genome-wide association study of different
      plumage color in Korean native chickens. We analyzed 60K SNP chips on 279
      chickens with GEMMA methods for GWAS and estimated the genetic heritability for
      plumage color. The estimated heritability suggests that plumage coloration is a
      polygenic trait. We found new loci associated with feather pigmentation at the
      genome-wide level and from the results infer that there are additional genetic
      effect for plumage color. The results will be used for selecting and breeding
      chicken for plumage color uniformity. 

PMID- 25049738
TI  - Identification and Association of SNPs in TBC1D1 Gene with Growth Traits in Two
      Rabbit Breeds.
AB  - The TBC1D1 plays a key role in body energy homeostasis by regulating the insulin
      stimulated glucose uptake in skeletal muscle. The present study aimed to identify
      the association between genetic polymorphisms of TBC1D1 and body weight (BW) in
      rabbits. Among the total of 12 SNPs detected in all 20 exons, only one SNP was
      non-synonymous (c.214G>A. p.G72R) located in exon 1. c.214G>A was subsequently
      genotyped among 491 individuals from two rabbit breeds by the high-resolution
      melting method. Allele A was the predominant allele with frequencies of 0.7780
      and 0.6678 in European white rabbit (EWR, n = 205) and New Zealand White rabbit
      (NZW, n = 286), respectively. The moderate polymorphism information content
      (0.25<PIC<0.50) was present in both breeds. The association analysis revealed
      that genotypes GA and AA had higher 35 d body weight (BW) than genotype GG in
      both EWR (p<0.01) and NEW (p<0.05). For the 56 d BW and 70 d BW traits, genotypes
      AA and GA were higher than genotype GG in both two breeds, the difference was not
      significant (p>0.05). Our results implied that the c.214G>A of TBC1D1 gene might
      be one of the candidate loci affecting the trait of 35 d BW in the rabbit. 

PMID- 25049739
TI  - A least squares regression model to detect quantitative trait Loci with polar
      overdominance in a cross of outbred breeds: simulation.
AB  - A least squares regression interval mapping model was derived to detect
      quantitative trait loci (QTL) with a unique mode of genomic imprinting, polar
      overdominance (POD), under a breed cross design model in outbred mammals. Tests
      to differentiate POD QTL from Mendelian, paternal or maternal expression QTL were
      also developed. To evaluate the power of the POD models and to determine the
      ability to differentiate POD from non-POD QTL, phenotypic data, marker data and a
      biallelic QTL were simulated on 512 F2 offspring. When tests for Mendelian versus
      parent-of-origin expression were performed, most POD QTL were classified as
      partially imprinted QTL. The application of the series of POD tests showed that
      more than 90% and 80% of medium and small POD QTL were declared as POD type.
      However, when breed-origin alleles were segregating in the grand parental breeds,
      the proportion of declared POD QTL decreased, which was more pronounced in a
      mating design with a small number of parents (F0 and F1). Non-POD QTL, i.e. with
      Mendelian or parent-of-origin expression (complete imprinting) inheritance, were
      well classified (>90%) as non-POD QTL, except for QTL with small effects and
      paternal or maternal expression in the design with a small number of parents, for
      which spurious POD QTL were declared. 

PMID- 25049740
TI  - Effects of Trichostatin A on Cumulus Expansion during Mouse Oocyte Maturation.
AB  - This study was conducted to investigate the effects of Trichostatin A (TSA) on
      cumulus expansion during mouse oocyte maturation. TSA treatment inhibited cumulus
      expansion and significantly reduced the cumulus expansion index (CEI) (p<0.05).
      To determine the underlying mechanism, the expression levels of several key
      factors that play crucial roles in cumulus expansion including components of
      extracellular matrix (ECM) (Has2, Ptgs2, Ptx3, and Tnfaip6) and Growth
      differentiation factor 9 (GDF9) were measured in control and TSA treated samples
      by real-time PCR. The effect of TSA on ERK phosphorylation (p-ERK1/2) in cumulus
      cells and GDF9 protein level in fully grown oocytes (FGOs) were detected by
      Western blotting. The expression levels of the ECM genes were significantly
      decreased (p<0.05) by TSA treatment while GDF9 expression did not response to TSA
      (p>0.05). TSA treatment blocked the activation of ERK1/2 (p<0.05) and had no
      significant effect on GDF9 protein expression (p>0.05). Collectively, these
      results suggested that TSA treatment altered ECM gene expression and blocked
      ERK1/2 activation to inhibit cumulus expansion in the mouse. 

PMID- 25049741
TI  - Influence of Ionophore Supplementation on Growth Performance, Dietary Energetics
      and Carcass Characteristics in Finishing Cattle during Period of Heat Stress.
AB  - Forty-eight crossbred heifers (378.1+/-18 kg) were used in a 56-d feeding trial
      (four pens per treatment in a randomised complete block design) to evaluate the
      influence of ionophore supplementation on growth performance, dietary energetics
      and carcass characteristics in finishing cattle during a period of heat stress.
      Heifers were fed a diet based on steam-flaked corn (2.22 Mcal NEm/kg) with and
      without an ionophore. Treatments were: i) control, no ionophore; ii) 30 mg/kg
      monensin sodium (RUM30); iii) 20 mg/kg lasalocid sodium (BOV20), and iv) 30 mg/kg
      lasalocid sodium (BOV30). Both dry matter intake (DMI) and climatic variables
      were measured daily and the temperature humidity index (THI) was estimated. The
      maximum THI during the study averaged 93, while the minimum was 70 (THI average =
      79.2+/-2.3). Compared to controls, monensin supplementation did not influence
      average daily gain, the estimated NE value of the diet, or observed-to-expected
      DMI, but tended (p = 0.07) to increase (4.8%) gain to feed. Compared to controls,
      the group fed BOV30 increased (p<=0.03) daily gain (11.8%), gain to feed (8.3%),
      net energy of the diet (5%), and observed-to-expected DMI (5.2%). Daily weight
      gain was greater (7.6%, p = 0.05) for heifers fed BOV30 than for heifers fed
      MON30. Otherwise, differences between the two treatments in DMI, gain to feed,
      and dietary NE were not statistically significant (p>0.11). Plotting weekly
      intakes versus THI, observed intake of controls was greater (p<0.05) at THI
      values <=77 than ionophore groups. When THI values were greater than 79, DMI of
      control and MON30 were not different (p = 0.42), although less than that of
      groups fed lasalocid (p = 0.04). Variation in energy intake was lower (p>0.05) in
      the ionophores group (CV = 1.7%) than in the control group (CV = 4.5%). Inclusion
      of ionophores in the diet resulted in relatively minor changes in carcass
      characteristics. It is concluded that ionophore supplementation did not
      exacerbate the decline of DM intake in heat-stressed cattle fed a high-energy
      finishing diet; on the contrary, it stabilised feed intake and favoured feed
      efficiency. Ionophore supplementation reduced estimated maintenance coefficients
      around 10% in finishing cattle during a period of heat stress. This effect was
      greatest for heifers supplemented with 30 mg lasalocid/kg of diet. 

PMID- 25049742
TI  - Effect of indigenous herbs on growth, blood metabolites and carcass
      characteristics in the late fattening period of hanwoo steers.
AB  - This study was conducted to evaluate the effects of indigenous herbal supplements
      on growth, blood metabolites and carcass characteristics in the late fattening
      period of Hanwoo steers. In a 6 month feeding trial, thirty Hanwoo steers (647+/
      32 kg) were allotted to one of 5 treatment groups, control (basal diet contained
      lasalocid), licorice, clove, turmeric and silymarin, with six steers per pen. All
      groups received ad libitum concentrate and 1 kg rice straw/animal/d throughout
      the feeding trial. Blood samples were collected at the beginning, middle, and the
      end of the experiment and the steers were slaughtered at the end. Blood glucose,
      triglyceride, total protein, and albumin concentrations were higher in the
      turmeric treatment compared with other treatments. Blood urea nitrogen and
      creatinine concentrations were highest (p<0.003 and p = 0.071, respectively) in
      steers treated with silymarin. Alanine aminotransferase activity was lower
      (p<0.06) for licorice and silymarin compared with the control group. There were
      no alterations in serum aspartate aminotransferase and gamma glutamyltransferase
      activities as a consequence of herb treatments (p = 0.203 and 0.135,
      respectively). Final body weight, body weight gain, average dairy gain and dry
      matter intake were not significantly different among treatments. Yield grade,
      marbling score and quality grade were higher for silymarin group than those of
      the control group (p<0.05). Therefore, the results suggest that silymarin can be
      used an effective dietary supplement as an alternative to antibiotic feed
      additive and a productivity enhancer, providing safe and more consumer acceptable
      alternative to synthetic compounds during the late fattening period of steers. 

PMID- 25049743
TI  - Effect of vitamin e and zinc supplementation on energy metabolites, lipid
      peroxidation, and milk production in peripartum sahiwal cows.
AB  - The study was conducted to evaluate the effect of vitamin E and zinc
      supplementation on energy metabolites, lipid peroxidation, and milk production in
      peripartum Sahiwal cows. For this, thirty-two pregnant dry Sahiwal cows were
      selected at sixty days prepartum and divided into four groups viz control, T1,
      T2, and T3 of eight each. Group T1 were supplemented with zinc at 60 ppm/d/cow,
      group T2 were supplemented with vitamin E at 1,000 IU/d/cow and group T3 were
      supplemented with combination of vitamin E at 1,000 IU/d/cow and zinc at 60
      ppm/d/cow during d 60 prepartum to d 90 postpartum. Blood samples were collected
      on d -60, -45, -30, -15, -7, -3, 0, 3, 7, 15, 30, 45, 60, 90, and 120 with
      respect to day of parturition and analysed for glucose, non esterified fatty
      acid, and thiobarbituric acid reactive substance. Body condition score was
      maintained significantly better (p<0.05) in T3 than in the control, T1 and T2
      groups. Overall glucose level was higher (p<0.05) in T3 than control, T1, and T2
      groups. Levels of nonesterified fatty acid, and thiobarbituric acid reactive
      substance were lower (p<0.05) in T3 than control, T1, and T2 groups. Milk yield
      was higher (p<0.05) in T3 than control, T1, and T2 groups. In conclusion, the
      present study indicated that the supplementation of vitamin E and zinc in
      peripartum Sahiwal cows enhanced milk production by reducing negative energy
      balance. 

PMID- 25049744
TI  - Blood haematology, serum thyroid hormones and glutathione peroxidase status in
      kacang goats fed inorganic iodine and selenium supplemented diets.
AB  - The effects of dietary supplementation of selenium (Se), iodine (I), and a
      combination of both on the blood haematology, serum free thyroxine (FT4) and free
      triiodothyronine (FT3) hormones and glutathione peroxidase enzyme (GSH-Px)
      activity were examined on twenty four (7 to 8 months old, 22+/-1.17 kg live
      weight) Kacang crossbred male goats. Animals were randomly assigned to four
      dietary treatments (6 animals in each group). Throughout 100 d of feeding trial,
      the animals of control group (CON) received a basal diet, while the other three
      groups were offered basal diet supplemented with 0.6 mg/kg diet DM Se (SS), or
      0.6 mg/kg diet DM I (PI), or a combination of both Se and I, each at 0.6 mg/kg
      diet DM (SSPI). The haematological attributes which are haemoglobin (Hb), red
      blood cell (RBC), packed cell volume (PCV), mean cell volume (MCV), white blood
      cells (WBC), band neutrophils (B Neut), segmented neutrophils (S Neut),
      lymphocytes (Lymph), monocytes (Mono), eosinophils (Eosin) and basophils (Baso)
      were similar among the four treatment groups, while serum levels of Se and I
      increased significantly (p<0.05) in the supplemented groups. The combined dietary
      supplementation of Se and I (SSPI) significantly increased serum FT3 in the
      supplemented animals. Serum GSH-Px activity increased significantly in the
      animals of SS and SSPI groups. It is concluded that the dietary supplementation
      of inorganic Se and I at a level of 0.6 mg/kg DM increased serum Se and I
      concentration, FT3 hormone and GSH-Px activity of Kacang crossbred male goats. 

PMID- 25049745
TI  - Changes of microbial population in the rumen of dairy steers as influenced by
      plant containing tannins and saponins and roughage to concentrate ratio.
AB  - The objective of this study was to investigate microbial population in the rumen
      of dairy steers as influenced by supplementing with dietary condensed tannins and
      saponins and different roughage to concentrate ratios. Four, rumen fistulated
      dairy steers (Bos indicus) were used in a 2*2 factorial arrangement in a 4*4
      Latin square design. The main factors were two roughage to concentrate ratios
      (R:C, 60:40 and 40:60) and two supplementations of rain tree pod meal (RPM) (0
      and 60 g/kg of total DM intake). Chopped 30 g/kg urea treated rice straw was used
      as a roughage source. All animals received feed according to respective R:C
      ratios at 25 g/kg body weight. The RPM contained crude tannins and saponins at 84
      and 143 g/kg of DM, respectively. It was found that ruminal pH decreased while
      ruminal temperature increased by a higher concentrate ratio (R:C 40:60) (p<0.05).
      In contrast, total bacterial, Ruminococus albus and viable proteolytic bacteria
      were not affected by dietary supplementation. Numbers of fungi, cellulolytic
      bacteria, Fibrobactor succinogenes and Ruminococus flavefaciens were higher while
      amylolytic bacteria was lower when steers were fed at 400 g/kg of concentrate.
      The population of Fibrobactor succinogenes, was found to be higher with RPM
      supplementation. In addition, the use of real-time PCR technique indicated that
      the population of protozoa and methanogens were decreased (p<0.05) with
      supplementation of RPM and with an increasing concentrate ratio. Supplementation
      of RPM and feeding different concentrate ratios resulted in changing the rumen
      microbes especially, when the animals were fed at 600 g/kg of concentrate and
      supplemented with RPM which significantly reduced the protozoa and methanogens
      population. 

PMID- 25049746
TI  - Effect of Bacillus Subtilis-based Direct-fed Microbials on Immune Status in
      Broiler Chickens Raised on Fresh or Used Litter.
AB  - Type of dietary direct-fed microbials (DFMs) or poultry litter could directly
      influence the composition of gut microbiota. Gut microbiota plays an important
      role in shaping the developing immune system and maintaining the homeostasis of
      the mature immune system in mammal and chickens. The present study was carried
      out to investigate the interaction among litter, DFMs and immunity in broiler
      chickens exposed to a field-simulated environment. Immune status of broiler
      chickens was assessed by serum antibodies against Eimeria spp. and Clostridium
      spp. and intestinal cytokine mRNA expression. The current experimental design had
      a 3 *2 factorial arrangement of treatments with three types of litter, i.e.,
      fresh litter or used litter that was obtained from a farm with no disease
      outbreak (used litter) or a farm with history of a gangrenous dermatitis outbreak
      (GD litter), and two dietary treatments with or without DFMs. It was found that
      either DFM addition or type of litter significantly affected anticoccidial
      antibody levels of broiler chickens at d 42. In general, dietary DFMs increased
      the anticoccidial antibodies in the fresh-litter raised chickens, but lowered the
      levels in the GD-litter raised chickens. Serum antibodies against Clostridium
      perfringens alpha-toxin were significantly (p<0.05) higher in chickens raised on
      GD litter compared with those raised on fresh litter. Cytokine mRNA expression
      was significantly (p<0.05) altered by either the type of litter or DFMs. Of
      interest, dietary DFMs lowered interferon-gamma, interleukin 1beta, and CXCLi2
      cytokine mRNA expression in chickens raised on fresh litter but increased them in
      GD-litter raised chickens. In conclusion, dietary DFMs modulate various immune
      parameters of broiler chickens, but the DFM-mediated effects were dependent upon
      the type of litter on which chickens were raised. 

PMID- 25049747
TI  - Effect of High Dietary Carbohydrate on the Growth Performance and Physiological
      Responses of Juvenile Wuchang Bream, Megalobrama amblycephala.
AB  - An optimum dietary carbohydrate content is important for maximum fish growth. In
      this study, we fed Wuchang bream (Megalobrama amblycephala) with either control
      diet (30.42%) or high carbohydrate diet (52.92%) for 90 d. Fish were fed to
      apparent satiation three times daily in an aquarium with automatic temperature
      control and circulated water. Growth performance, plasma biochemical parameters,
      hepatic morphology and enzyme activities were determined. It was shown that
      compared to fish fed control diet, fish fed high carbohydrate diet had higher
      plasma triglyceride and cortisol levels for d 90, and lower alkaline phosphatase
      level for d 45, lower hepatic superoxide dismutase and total antioxidative
      capacity for d 90, higher malondialdehyde for d 45 and glycogen content for d 45
      and 90 (p<0.05). Histological and transmission electron microscopy studies showed
      that hepatocytes of fish fed high carbohydrate diet contained large lipid
      droplets, causing displacement of cellular organelles to periphery of
      hepatocytes. The relative level of hepatic heat shock protein 70 (HSP70) mRNA of
      Wuchang bream fed high carbohydrate diet was significantly higher than that of
      fish fed the control diet for 90 d (p<0.05). These changes led to decreased
      specific growth rate and increased feed conversion ratio (p<0.05). Upon hypoxia
      challenge, fish fed high carbohydrate diet had higher cumulative mortality than
      those fed the control diet (p<0.05). These results suggested that high dietary
      carbohydrate (52.92%) was detrimental to the growth performance and health of
      Wuchang bream. 

PMID- 25049748
TI  - Standardized total tract digestibility of phosphorus in copra expellers, palm
      kernel expellers, and cassava root fed to growing pigs.
AB  - An experiment was conducted to determine the apparent total tract digestibility
      (ATTD) and standardized total tract digestibility (STTD) of phosphorus (P) in
      copra expellers (CE), palm kernel expellers (PKE), and cassava root (CR). Eight
      barrows (initial BW of 40.0 kg, SD = 4.5) were individually housed in metabolism
      crates. A replicated 4*3 incomplete Latin square design was employed involving 4
      dietary treatments, 3 periods, and 8 animals. Three experimental diets contained
      40% CE, PKE or CR as the only source of P. A P-free diet mainly based on corn
      starch, sucrose, and gelatin was also prepared to estimate the basal endogenous
      loss of P. The marker-to-marker method was used for fecal collection. Values for
      the ATTD of P in the CE and PKE were greater than in the CR (46.0 and 39.7 vs 
      14.0%; p<0.05). However, the STTD of P did not differ greatly among the test
      ingredients (56.5, 49.0, and 43.2% in the CE, PKE, and CR, respectively). In
      conclusion, the ATTD of P values in CE and PKE were greater than that in CR, but
      the STTD of P did not differ greatly among CE, PKE, and CR. 

PMID- 25049749
TI  - Effects of graded levels of montmorillonite on performance, hematological
      parameters and bone mineralization in weaned pigs.
AB  - The aim of this study was to investigate the effects of graded levels of
      montmorillonite, a constituent of clay, on performance, hematological parameters
      and bone mineralization in weaned pigs. One hundred and twenty, 35-d-old
      crossbred pigs (Duroc*Large White*Landrace, 10.50+/-1.20 kg) were used in a 28-d
      experiment and fed either an unsupplemented corn-soybean meal basal diet or
      similar diets supplemented with 0.5, 1.0, 2.5 or 5.0% montmorillonite added at
      the expense of wheat bran. Each treatment was replicated six times with four pigs
      (two barrows and two gilts) per replicate. Feed intake declined (linear and
      quadratic effect, p< 0.01) with increasing level of montmorillonite while feed
      conversion was improved (linear and quadratic effect, p<0.01). Daily gain was
      unaffected by dietary treatment. Plasma myeloperoxidase declined linearly (p =
      0.03) with increasing dietary level of montmorillonite. Plasma malondialdehyde
      and nitric oxide levels were quadratically affected (p<0.01) by montmorillonite
      with increases observed for pigs fed the 0.5 and 1.0% levels which then declined
      for pigs fed the 2.5 and 5.0% treatments. In bone, the content of potassium,
      sodium, copper, iron, manganese and magnesium were decreased (linear and
      quadratic effect, p<0.01) in response to an increase of dietary montmorillonite.
      These results suggest that dietary inclusion of montmorillonite at levels as high
      as 5.0% does not result in overt toxicity but could induce potential oxidative
      damage and reduce bone mineralization in pigs. 

PMID- 25049750
TI  - Separation of Phosvitin from Egg Yolk without Using Organic Solvents.
AB  - The objective of this study was to develop a new method to separate phosvitin
      from egg yolk without using organic solvents. Phosvitin was extracted from yolk
      granules using 10% NaCl or 10% (NH4)2SO4 (final concentration) and then treated
      with heat to precipitate the lipoproteins from the extracted solution. The
      optimal pH for the phosvitin extraction from yolk granules was determined, and
      the iron-binding ability of the extracted phosvitin (final product) was tested.
      Adding 10% (NH4)2SO4 disrupted the granules, and the subsequent thermal treatment
      at 90 degrees C for 1 h precipitated low density and high density lipoproteins,
      which enabled separation of phosvitin by centrifugation. The phosvitin
      concentration in the extract was significantly higher when the pH of the solution
      was adjusted to pH >=9. The purity and recovery rate of phosvitin at the end of
      the separation process were approximately 78% and 56%, respectively. The
      separated phosvitin was confirmed to have ferrous and ferric iron binding
      ability. The advantages of this new method compared with the traditional methods
      include no organic solvents and high-priced equipment are needed for the
      separation. Also, this method is more environment and consumer friendly than that
      of the traditional methods. 

PMID- 25049751
TI  - Carcass characteristics and qualitative attributes of pork from immunocastrated
      animals.
AB  - An investigation was carried out to assess the carcass characteristics and meat
      quality aspects of immunocastrated male pigs of medium genetic potential for lean
      meat deposition in carcass (53 to 55%). When the crossbred Large White x Landrace
      pigs (n = 45) were 70 days old, they were distributed in a totally randomized
      design in three treatments (castrated males, females and immunocastrated males)
      with three replicates of five animals. The pigs were slaughtered when they were
      140 days old. Carcass temperature and pH were recorded twice, at 45 min and 24 h
      after slaughter. The carcasses were evaluated for hot and cold carcass yield,
      commercial cuts yield, length and depth, back fat thickness, loin eye area and
      lean meat percentage. The Longissimus dorsi muscle was extracted for analysis of
      color (L*, a*, b*), exudate loss, cooking loss and centesimal and sensorial
      analysis of the meat. There were no significant differences for the evaluated
      parameters between castrated males, immunocastrated males and females, except for
      backfat thickness between the 7th and 8th thoracic vertebra and the point P2
      (lower for immunocastrated males) and carcass temperature at 45 min post
      slaughter (higher in immunocastrated males), however, this did not interfer with
      the rate of pH decrease post mortem and the meat quality. The results from this
      research did not indicate a benefit of immunocastration on carcass
      characteristics of pigs of medium genetic potential for lean meat deposition in
      carcass, when compared to surgical castration. 

PMID- 25049752
TI  - Slaughtering age effect on carcass traits and meat quality of italian heavy
      draught horse foals.
AB  - The present work describes the effect of slaughtering age on horse carcass traits
      and on meat quality. Eighteen male Italian heavy draught horse (IHDH) breed foals
      were employed in the study. Soon after foaling they were randomly subdivided in 3
      groups according to 3 age at slaughtering classes: 6 months old, 11 months old
      and 18 months old. Live weight, hot carcass weight and dressing percentage of
      each animal were recorded. After slaughtering, meat samples were collected from
      Longissimus Dorsi muscle between 13th and 18th thoracic vertebra of each animal
      and then analyzed. The right half carcass of each animal was then divided in
      cuts. Each one was subdivided into lean, fat and bones. Then, the classification
      of the lean meat in first and second quality cuts was performed according to the
      butchers' customs. Older animals were characterized by a lower incidence of first
      quality cuts (p<0.01) on carcass. Younger animals showed greater content in
      protein (p<0.01). Fatty acid profile showed an increasing trend of PUFA connected
      to the increasing of slaughtering age (p<0.05). The unsaturation index of
      intramuscular fatty acids was not affected by slaughtering age, confirming that
      horse meat, if compared to beef, is more suitable from a nutritional point of
      view. Season influenced reproduction, birth as well as production aspects of this
      species. The different slaughtering age could represent the way to produce meat
      of IHDH foals during the entire year without change in the qualitative standard
      expected by consumers. 

PMID- 25049753
TI  - Molecular Characterization and Expression Analysis of Ribosomal Protein S6 Gene
      in the Cashmere Goat (Capra hircus).
AB  - Ribosomal protein (rp) S6 is the substrate of ribosomal protein S6K (S6 kinase)
      and is involved in protein synthesis by mTOR/S6K/S6 signaling pathway. Some S6
      cDNA have been cloned in mammals in recent years but has not been identified in
      the goat. To facilitate such studies, we cloned the cDNA encoding Cashmere goat
      (Capra hircus) S6 (GenBank accession GU131122) and then detected mRNA expression
      in seven tissues by real time PCR and protein expression in testis tissue by
      immunohistochemisty. Sequence analysis indicated that the obtained goat S6 was a
      808 bp product, including a 3' untranslated region of 58 bp and an open reading
      frame of 750 bp which predicted a protein of 249 amino acids. The predicted amino
      acid sequence was highly homologous to cattle, human, mouse and rat S6.
      Expression analysis indicated S6 mRNA was expressed extensively in detected
      tissues and S6 protein was expressed in testis tissue. 

PMID- 25049754
TI  - Isolation and Characterization of Novel Denitrifying Bacterium Geobacillus sp. SG
      01 Strain from Wood Chips Composted with Swine Manure.
AB  - Nitrate contamination in ground and surface water is an increasingly serious
      environmental problem and only a few bacterial strains have been identified that
      have the ability to remove nitrogen pollutants from wastewater under thermophilic
      conditions. We therefore isolated thermophilic facultative bacterial strains from
      wood chips that had been composted with swine manure under aerated high
      temperature conditions so as to identify strains with denitrifying ability. Nine
      different colonies were screened and 3 long rod-shaped bacterial strains
      designated as SG-01, SG-02, and SG-03 were selected. The strain SG-01 could be
      differentiated from SG-02 and SG-03 on the basis of the method that it used for
      sugar utilization. The 16S rRNA genes of this strain also had high sequence
      similarity with Geobacillus thermodenitrificans 465(T) (99.6%). The optimal
      growth temperatures (55 degrees C), pH values (pH 7.0), and NaCl concentrations
      (1%) required for the growth of strain SG-01 were established. This strain
      reduced 1.18 mM nitrate and 1.45 mM nitrite in LB broth after 48 h of incubation.
      These results suggest that the G. thermodenitrificans SG-01 strain may be useful
      in the removal of nitrates and nitrites from wastewater generated as a result of
      livestock farming. 

PMID- 25049755
TI  - Characterizations of Shell and Mantle Edge Pigmentation of a Pacific Oyster,
      Crassostrea gigas, in Korean Peninsula.
AB  - The objectives of this study were to investigate color patterns of shell and
      mantle edge pigmentation of a Pacific oyster, C. gigas, and to estimate variance
      components of the two colors. A sample of 240 F0 oysters was collected from six
      aquaculture farms in Tongyeong, Korea to measure shell color and mantle edge
      pigmentation. Among the F0s, male and female individuals with black (white) shell
      and black (white) mantle edge were selected and mated to generate three F1 full
      sib black (white) cross families (N = 265). Two and four F2 cross families (N =
      286) were also produced from black and white F1 selected individuals,
      respectively. Variance component estimates due to residuals and families within
      color were obtained using SAS PROC VARCOMP procedures to estimate heritability of
      shell and mantle edge pigmentation. In the F0 generation, about 29% (11%) had
      black (white) color for both shell and mantle edge. However, in the F1 and F2
      black (white) cross families, 75% (67%) and 100% (100%) of oysters had black
      (white) shell colors, and 59% (23%) and 79% (55%) had black (white) mantle edge,
      respectively. Spearman correlation coefficients between shell and mantle edge
      color were 0.25, 0.74, and 0.92 in F0, F1, and F2 generations, respectively,
      indicating that, with generations of selection process, an individual with black
      (white) shell color is more likely to have black (white) mantle edge
      pigmentation. This suggests that shell color could be a good indicator trait for
      mantle edge pigmentation if selection of both the colors is implemented for a
      couple of generations. Estimates of heritability were 0.41 and 0.77 for shell
      color and 0.27 and 0.08 for mantle edge pigmentation in the F1 and F2
      generations, respectively, indicating that, in general, significant proportions
      of phenotypic variations for the shell and mantle edge colors are explained by
      genetic variations between individuals. These results suggest that the two color
      traits are inheritable and correlated, enabling effective selection on shell and
      mantle edge color. 

PMID- 25049756
TI  - Reference gene screening for analyzing gene expression across goat tissue.
AB  - Real-time quantitative PCR (qRT-PCR) is one of the important methods for
      investigating the changes in mRNA expression levels in cells and tissues.
      Selection of the proper reference genes is very important when calibrating the
      results of real-time quantitative PCR. Studies on the selection of reference
      genes in goat tissues are limited, despite the economic importance of their meat
      and dairy products. We used real-time quantitative PCR to detect the expression
      levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1,
      GAPDH and EEF1A2) in ten tissues types sourced from Boer goats. The optimal
      reference gene combination was selected according to the results determined by
      geNorm, NormFinder and Bestkeeper software packages. The analyses showed that
      tissue is an important variability factor in genes expression stability. When all
      tissues were considered, 18S, TBP and HMBS is the optimal reference combination
      for calibrating quantitative PCR analysis of gene expression from goat tissues.
      Dividing data set by tissues, ACTB was the most stable in stomach, small
      intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in
      liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable
      information about the goat reference genes that can be used in order to perform a
      proper normalisation when relative quantification by qRT-PCR studies is
      undertaken. 

PMID- 25049757
TI  - Accurate estimation of effective population size in the korean dairy cattle based
      on linkage disequilibrium corrected by genomic relationship matrix.
AB  - Linkage disequilibrium between markers or genetic variants underlying interesting
      traits affects many genomic methodologies. In many genomic methodologies, the
      effective population size (Ne) is important to assess the genetic diversity of
      animal populations. In this study, dairy cattle were genotyped using the Illumina
      BovineHD Genotyping BeadChips for over 777,000 SNPs located across all autosomes,
      mitochondria and sex chromosomes, and 70,000 autosomal SNPs were selected
      randomly for the final analysis. We characterized more accurate linkage
      disequilibrium in a sample of 96 dairy cattle producing milk in Korea. Estimated
      linkage disequilibrium was relatively high between closely linked markers (>0.6
      at 10 kb) and decreased with increasing distance. Using formulae that related the
      expected linkage disequilibrium to Ne, and assuming a constant actual population
      size, Ne was estimated to be approximately 122 in this population. Historical Ne,
      calculated assuming linear population growth, was suggestive of a rapid increase
      Ne over the past 10 generations, and increased slowly thereafter. Additionally,
      we corrected the genomic relationship structure per chromosome in calculating
      r(2) and estimated Ne. The observed Ne based on r(2) corrected by genomics
      relationship structure can be rationalized using current knowledge of the history
      of the dairy cattle breeds producing milk in Korea. 

PMID- 25049758
TI  - Effects of Trichostatin A on In vitro Development of Porcine Embryos Derived from
      Somatic Cell Nuclear Transfer.
AB  - Many different approaches have been developed to improve the efficiency of animal
      cloning by somatic cell nuclear transfer (SCNT), one of which is to modify
      histone acetylation levels using histone deacetylase inhibitors (HDACi) such as
      trichostatin A (TSA). In the present study, we examined the effect of TSA on in
      vitro development of porcine embryos derived from SCNT. We found that TSA
      treatment (50 nM) for 24 h following oocyte activation improved blastocyst
      formation rates (to 22.0%) compared with 8.9% in the non-treatment group and
      total cell number of the blastocysts for determining embryo quality also
      increased significantly (88.9->114.4). Changes in histone acetylation levels as a
      result of TSA treatment were examined using indirect immunofluorescence and
      confocal microscopy scanning. Results showed that the histone acetylation level
      in TSA-treated embryos was higher than that in controls at both acetylated
      histone H3 lysine 9 (AcH3K9) and acetylated histone H4 lysine 12 (AcH4K12). Next,
      we compared the expression patterns of seven genes (OCT4, ID1; the pluripotent
      genes, H19, NNAT, PEG1; the imprinting genes, cytokeratin 8 and 18; the
      trophoblast marker genes). The SCNT blastocysts both with and without TSA
      treatment showed lower levels of OCT4, ID1, cytokeratin 8 and 18 than those of
      the in vivo blastocysts. In the case of the imprinting genes H19 and NNAT, except
      PEG1, the SCNT blastocysts both with and without TSA treatment showed higher
      levels than those of the in vivo blastocysts. Although the gene expression
      patterns between cloned blastocysts and their in vivo counterparts were different
      regardless of TSA treatment, it appears that several genes in NT blastocysts
      after TSA treatment showed a slight tendency toward expression patterns of in
      vivo blastocysts. Our results suggest that TSA treatment may improve
      preimplantation porcine embryo development following SCNT. 

PMID- 25049760
TI  - In vitro Evaluation of Different Feeds for Their Potential to Generate Methane
      and Change Methanogen Diversity.
AB  - Optimization of the dietary formulation is the most effective way to reduce
      methane. Nineteen feed ingredients (brans, vegetable proteins, and grains) were
      evaluated for their potential to generate methane and change methanogen diversity
      using an in vitro ruminal fermentation technique. Feed formulations categorized
      into high, medium and low production based on methane production of each
      ingredient were then subjected to in vitro fermentation to determine the real
      methane production and their effects on digestibility. Methanogen diversity among
      low, medium and high-methane producing groups was analyzed by PCR-DGGE. The
      highest methane production was observed in Korean wheat bran, soybean and perilla
      meals, and wheat and maize of brans, vegetable protein and cereal groups,
      respectively. On the other hand, corn bran, cotton seed meal and barley led to
      the lowest production in the same groups. Nine bacteria and 18 methanogen 16s
      rDNA PCR-DGGE dominant bands were identified with 83% to 99% and 92% to 100%
      similarity, respectively. Overall, the results of this study showed that methane
      emissions from ruminants can be mitigated through proper selection of feed
      ingredients to be used in the formulation of diets. 

PMID- 25049759
TI  - Effects of physical form and urea treatment of rice straw on rumen fermentation,
      microbial protein synthesis and nutrient digestibility in dairy steers.
AB  - This study was designed to determine the effect of physical form and urea
      treatment of rice straw on rumen fermentation, microbial protein synthesis and
      nutrient digestibility. Four rumen-fistulated dairy steers were randomly assigned
      according to a 2 (2 factorial arrangement in a 4 (4 Latin square design to
      receive four dietary treatments. Factor A was roughage source: untreated rice
      straw (RS) and urea-treated (3%) rice straw (UTRS), and factor B was type of
      physical form of rice straw: long form rice straw (LFR) and chopped (4 cm) rice
      straw (CHR). The steers were offered the concentrate at 0.5% body weight (BW) /d
      and rice straw was fed ad libitum. DM intake and nutrient digestibility were
      increased (p<0.05) by urea treatment. Ruminal pH were decreased (p<0.05) in UTRS
      fed group, while ruminal ammonia nitrogen (NH3-N) and blood urea nitrogen (BUN)
      were increased (p<0.01) by urea treatment. Total volatile fatty acid (VFA)
      concentrations increased (p<0.01) when steers were fed UTRS. Furthermore, VFA
      concentrations were not altered by treatments (p>0.05), except propionic acid
      (C3) was increased (p<0.05) in UTRS fed group. Nitrogen (N) balance was affected
      by urea treatment (p<0.05). Microbial protein synthesis (MCP) synthesis were
      greater by UTRS and CHR group (p<0.05). The efficiency of microbial N synthesis
      was greater for UTRS than for RS (p<0.05). From these results, it can be
      concluded that using the long form combined with urea treatment of rice straw
      improved feed intake, digestibility, rumen fermentation and efficiency of
      microbial N synthesis in crossbred dairy steers. 

PMID- 25049761
TI  - Relationship between the Methane Production and the CNCPS Carbohydrate Fractions
      of Rations with Various Concentrate/roughage Ratios Evaluated Using In vitro
      Incubation Technique.
AB  - The objective of the trial was to study the relationship between the methane
      (CH4) production and the Cornell Net Carbohydrate and Protein System (CNCPS)
      carbohydrate fractions of feeds for cattle and the suitability of CNCPS
      carbohydrate fractions as the dietary variables in modeling the CH4 production in
      rumen fermentation. Forty-five rations for cattle with the concentrate/roughage
      ratios of 10:90, 20:80, 30:70, 40:60, and 50:50 were formulated as feed samples.
      The Menke and Steingass's gas test was used for the measurement of CH4
      production. The feed samples were incubated for 48 h and the CH4 production was
      analyzed using gas chromatography. Statistical analysis indicated that the CH4
      production (mL) was closely correlated with the CNCPS carbohydrate fractions (g),
      i.e. CA (sugars); CB1 (starch and pectin); CB2 (available cell wall) in a
      multiple linear pattern: CH4 = (89.16+/-14.93) CA+ (124.10+/-13.90) CB1+(30.58+/
      11.72) CB2+(3.28+/-7.19), R(2) = 0.81, p<0.0001, n = 45. Validation of the model
      using 10 rations indicated that the CH4 production of the rations for cattle
      could accurately be predicted based on the CNCPS carbohydrate fractions. The
      trial indicated that the CNCPS carbohydrate fractions CA, CB1 and CB2 were
      suitable dietary variables for predicting the CH4 production in rumen
      fermentation in vitro. 

PMID- 25049762
TI  - Grazing behavior and locomotion of young bulls receiving different nutritional
      plans in a tropical pasture.
AB  - The objectives of this study were to compare visual observation and an electronic
      grazing time method and to evaluate the effects of nutritional plans on intake,
      grazing behavior and horizontal and vertical locomotion of young bulls in a
      tropical pasture. Thirty-nine Nellore young bulls with an average body weight of
      345+/-9.3 kg kept in pasture were used. The experimental treatments consisted of:
      restricted: animals kept in a plot with a low mass of forage receiving mineral
      mixture only; control: animals receiving mineral mixture only; HPHC: a high
      protein and high carbohydrate supplement; HPLC: a high protein and low
      carbohydrate supplement; LPHC: a low protein and high carbohydrate supplement;
      LPLC: a low protein and low carbohydrate supplement. GPS collars equipped with
      activity sensors were used. Information about head position, latitude, longitude
      and altitude were recorded. Daytime grazing behavioral patterns monitored by a
      continuous focal animal recording method was compared to behavior estimated by
      the activity sensor. Feed intake was estimated by a marker method. The Restricted
      group presented lower (p<0.05) intake of dry matter and TDN. However, difference
      in dry matter intake was not found (p>0.05) between non-supplemented and
      supplemented animals. Difference was not found (p>0.05) in daytime grazing time
      obtained by visual observation or the activity sensor method. The restricted
      group showed longer (p<0.05) grazing time (9.58 h/d) than other groups, but
      difference was not found (p>0.05) in the grazing time between Control (8.35 h/d)
      and supplemented animals (8.03 h/d). The Restricted group presented lower
      (p<0.05) horizontal locomotion distance (2,168 m/d) in comparison to other groups
      (2,580.6 m/d). It can be concluded that the use of activity sensor methods can be
      recommended due to their being similar to visual observation and able to record
      24-h/d. While supplements with high carbohydrates reduce pasture intake, they do
      not change grazing behavior. Moderate supplementation (until 50% of protein
      requirement and 30% of energy requirement) of beef cattle on tropical pasture has
      no effect on daily locomotion. 

PMID- 25049763
TI  - Effects of dietary electrolyte balance on growth performance, nitrogen metabolism
      and some blood biochemical parameters of growing rabbits.
AB  - The effects of different dietary electrolyte balance (DEB) on growth performance,
      nitrogen (N) metabolism and some blood biochemical parameters were investigated
      in 2 to 3 months old growing rabbits. A total of 150 growing rabbits of 2 months
      age were randomly divided into five groups according to average body weight, with
      30 rabbits in each group. The DEB levels of the five experimental diets were 
      154, -3.16, +201, +347, and +500 meq/kg of dry matter (DM), respectively. There
      was a 7-d adaptation period and a 23-d experimental period. The results showed
      that the DEB levels had a quadratic affect on the average daily feed intake
      (ADFI) (p<0.001). The greatest ADFI was achieved when the DEB level was +201
      meq/kg DM. Fecal N (FN) content linearly decreased (0.047), while digestible N
      (DN), retained N (RN), efficiency of intake N converted into digestible N (DN/IN)
      and the efficiency of intake N converted into retained N (RN/IN) linearly
      increased with the DEB increase (0.020, 0.004, 0.021, and 0.049, respectively).
      Serum phosphorus (P) ion content linearly increased with the DEB increase (p =
      0.036). The DEB had a quadratic relationship with serum anion gap (AG) (p =
      0.002) and serum parathyroid hormone (PTH) content (p = 0.016). The DEB levels
      quadratically affected base excess (BE) in the plasma (p<0.001). In conclusion,
      the DEB unaffected growth performance but affected feed intake, N metabolism and
      some blood biochemical parameters of growing rabbits. 

PMID- 25049764
TI  - By-product of Tropical Vermicelli Waste as a Novel Alternative Feedstuff in
      Broiler Diets.
AB  - Two experiments were conducted to determine physical and chemical properties of
      vermicelli waste (VW) and effect of VW inclusion levels on growth performance of
      broilers. In experiment 1, VW samples were randomly collected from vermicelli
      industry in Thailand to analyze nutritional composition. Vermicelli waste
      contained 9.96% moisture, 12.06% CP, 32.30% crude fiber (CF), and 0.57% ether
      extract (EE), as DM basis. The ratio of insoluble:soluble non-starch
      polysaccharide (NSP) was 43.4:8.9. A total of 120 chicks (6 pens per treatment
      and 10 chicks per pen) were fed a corn-soybean meal-based diet or 20% VW
      substituted diet to determine the apparent metabolizable energy corrected for
      nitrogen retention (AMEn) of VW. The AMEn of VW was 1,844.7+/-130.71 kcal/kg. In
      experiment 2, a total of 1,200 chicks were randomly allotted to 1 of 4 dietary
      treatments for 42-d growth assay. There were 300 chicks with 6 pens per treatment
      and 50 chicks per pen. The dietary treatments contained 0%, 5%, 10%, or 15% VW,
      respectively. All diets were formulated to be isocaloric and isonitrogenous. From
      0 to 18 d of age chicks fed VW diets had higher (p<0.001) feed conversion ratio
      (FCR) compared with those fed the control diet. No difference was observed during
      grower and finisher phase (19 to 42 d). Chicks fed VW diets had lower relative
      weight of abdominal fat (p<0.001) but higher relative weight of gizzard (p<0.05)
      than those of chicks fed the control diet. Increasing VW inclusion levels
      increased ileal digesta viscosity (p<0.05) and intestinal villus height of chicks
      (p< 0.001). For apparent total tract digestibility assay, there were 4 metabolic
      cages of 6 chicks that were fed experimental treatment diets (the same as in the
      growth assay) in a 10-d total excreta collection. Increasing VW inclusion levels
      linearly decreased (p<0.05) apparent total tract digestibility of DM and CF. 

PMID- 25049765
TI  - Growth Performance, Carcass Traits and Serum Mineral Chemistry as Affected by
      Dietary Sodium and Sodium Salts Fed to Broiler Chickens Reared under Phase
      Feeding System.
AB  - A basal diet (0.8 g/kg dNa) was formulated in which each of the two sources
      (NaHCO3 and Na2SO4) were supplemented in such a way to attain four levels (1.7,
      2.6, 3.5, and 4.4 g/kg) of total dNa, respectively, under 4*2 factorial
      arrangement. Eight dietary treatments were replicated four times, with 40 birds
      in each replicate (n = 1,280). The diets supplemented with Na2SO4 to attain
      higher levels of dNa showed highest BW gain and feed intake (FI) during d 1 to 10
      (interaction effects) while 2.6 g/kg dNa exhibited improved BW gain and gain:feed
      (FG) during d 11 to 20. Linear rise in daily water intake (DWI) was associated
      with diets containing increasing dNa during d 1 to 42 (p<=0.036). During the
      first 10 d, DWI:FI was found highest in NaHCO3 diets while Na2SO4 diets showed
      highest DWI:FI during last 10 d of the experiment (p<=0.036). Increasing dNa and
      changing Na2SO4 with NaHCO3 salt increased pH and resulted in poor growth
      performance. Dressing weight (p<=0.001) and abdominal fat (p<=0.001; quadratic
      effect) were reduced, whereas breast (p<=0.001) and thigh (p<0.001) weights were
      aggravated with increasing dNa (linear effects). Present findings suggested
      higher levels of dNa from Na2SO4 as the supplemental salt in broiler diets would
      produce better growth performance, especially in first ten days of life, and
      improve carcass and body organ characteristics. 

PMID- 25049766
TI  - Effect of the Addition of Schisandra chinensis Powder on the Physico-chemical
      Characteristics of Sausage.
AB  - The individual and interactive effects of Schisandra chinensis powder (SCP) and
      sodium nitrite additions on color, pH, water holding capacity, residual nitrite,
      2-thiobarbituric acid reactive substances (TBARS), volatile basic nitrogen,
      texture properties, fatty acids, amino acids and sensory evaluation of cooked
      pork sausages were investigated after 20 d of storage at 4 degrees C. The powders
      (0, 0.5 and 1.0%) were added to sausages either alone or in combination with
      nitrite (0 and 100 ppm). SCP added-sausages showed lower L* (lightness) and W
      (whiteness) values, and higher b* (yellowness) values than sausage containing no
      nitrite, and exhibited the highest a(*) values at a 0.5% addition (p<0.05).
      Residual nitrite and TBARS values were found to be significantly reduced as the
      addition levels of SCP increased (p<0.05). As the addition of SCP increased, the
      sausage showed gradually decreased brittleness, cohesiveness, springiness,
      gumminess and chewiness, while adhesiveness increased. Polyunsaturated fatty
      acid, n-6 and n-6/n-3 fatty acid ratio concentrations were significantly higher
      in sausages containing SCP (p<0.05). The addition of SCP to sausage significantly
      (p<0.05) increased the ammonia content (by 0.5% SCP) and aromatic amino acid
      concentrations (by 1.0% SCP) (p<0.05). Inclusion of SCP in sausage meat resulted
      in a significant deterioration in quality characteristics of flavor, springiness,
      juiciness and overall acceptability (p<0.05). As expected, the observed changes
      in a*, W, pH, shear force, texture property, TBARS, fatty acid, amino acid and
      sensory score of sausages, depended on the rate of addition of nitrite (p<0.05).
      These results suggest that SCP addition is not an effective way of improving the
      sensory evaluation of sausages, but may beneficially affect TBARS, nitrite
      scavenging activity, fatty acid and amino acid content in pork sausages. 

PMID- 25049767
TI  - The Effects of Pre-slaughter Stress and Season on the Activity of Plasma Creatine
      Kinase and Mutton Quality from Different Sheep Breeds Slaughtered at a
      Smallholder Abattoir.
AB  - The objective of the current study was to determine the effect of pre-slaughter
      stress, season and breed on the activity of plasma creatine kinase (CK) and the
      quality of mutton. One hundred and seventy-three (173) castrated sheep from
      Dormer (DM), South African Mutton Merino (SAMM), Dorper (DP) and Blackhead
      Persian (BP) sheep breeds were used in the study. The animals were grouped
      according to age-groups as follows: Group 1 (6 to 8 months), Group 2 (9 to 12
      months) and Group 3 (13 to 16 months). Blood samples were collected during
      exsanguinations using disposable vacutainer tubes for CK analysis. Representative
      samples of the Muscularis longissimuss thoracis et. lumborum (LTL) were collected
      from 84 castrated sheep, of different breeds (28 per breed) 24 h after slaughter.
      The following physico-chemical characteristics of mutton were determined; meat pH
      (pH24), color (L*, a* and b*), thawing and cooking losses and Warner Braztler
      Shear Force (WBSF). The activity of plasma CK was significantly higher (p<0.001)
      in summer (1,026.3+/-105.06) and lower in winter (723.3+/-77.75). There were
      higher values for L* (33.7+/-0.94), b* (11.5+/-0.48) and WBSF (29.5+/-1.46) in
      summer season than in winter season; L* (29.4+/-0.64), b* (10.2+/-0.33) and WBSF
      (21.2+/-0.99). The activity of plasma CK was influenced by the type of breed with
      Dormer having the highest (p>0.001) levels (1,358.6+/-191.08) of CK. South
      African Mutton Merino had higher values for pH24 (5.9+/-0.06), L* (34.2+/-0.97),
      b* (12.2+/-0.50) and WBSF (26.8+/-1.51) and Blackhead Persian had higher values
      (35.5+/-2.17) for cooking loss (CL%) than the other breeds. Computed Principal
      Component Analyses (PCA) on the activity of plasma CK and physico-chemical
      characteristics of mutton revealed no correlations between these variables.
      However, positive correlations were observed between pH24, L*, a*, b*, CL% and
      WBSF. Relationships between pre-slaughter stress, CK activity and physico
      chemical characteristics of mutton were also observed. It was therefore concluded
      that although mutton quality and creatine kinase were not related, pre-slaughter
      stress, season and breed affected the activity of creatine kinase and mutton
      quality. 

PMID- 25049768
TI  - Comparison of Physicochemical and Sensory Properties between Cholesterol-removed
      Gouda Cheese and Gouda Cheese during Ripening.
AB  - This study was performed to compare physicochemical and sensory properties of
      cholesterol-removed Gouda cheese (CRGC) and Gouda cheese made in the laboratory
      during ripening. Composition, short-chain free fatty acids (SCFFA), texture,
      color, and sensory properties were measured. In chemical composition analyses,
      moistures were significantly different between control cheeses (42.86%) and
      sample cheese (48.32%) (p<0.05). But fat and protein in the control and the
      sample were 32.77, 22.45 and 31.35, 20.39%, respectively, and were not
      significantly different (p>0.05). The amount of cholesterol in control was 82.52
      mg/100 g and the percentage of cholesterol removal was 90.7%. SCFFA increased
      gradually during ripening and its level of CRGC increased and significantly
      different from that of control (p<0.05). The texture, hardness, gumminess, and
      chewiness were significantly increased, but cohesiveness and springiness were not
      increased in both cheeses during ripening periods (p>0.05). In comparison of the
      control and sample cheeses, hardness, and springiness were not significantly
      different, but cohesiveness, gumminess, and chewiness were different (p<0.05). In
      color measurement, all color values were not different between CRGC and control
      (p>0.05). However, L* value decreased, while a* and b* values tended to increase
      significantly (p<0.05). In sensory properties, appearance, aroma, flavor and
      taste, and texture were significantly increased except buttery and nutty in aroma
      and sweetness in taste in both cheeses, and were not significantly different
      between the control and sample cheeses during ripening (p>0.05). Therefore, this
      study suggests that the quality of cholesterol-removed Gouda cheese is not
      different from the control cheese. 

PMID- 25049769
TI  - Effect of Modified Atmosphere Packaging and Vacuum Packaging on Quality
      Characteristics of Low Grade Beef during Cold Storage.
AB  - Many studies have been carried out with respect to packaging methods and
      temperature conditions of beef. However, the effects of packaging methods and
      temperature conditions on the quality characteristics have not been extensively
      studied in low-grade beef. Low-grade beef samples were divided into 3 groups (C:
      ziplock bag packaging, T1: vacuum packaging, and T2: modified atmosphere
      packaging (MAP), CO2/N2 = 3:7) and samples were stored at 4 degrees C for 21
      days. The water-holding capacity (WHC) was significantly lower in T1 than in the
      other samples up to 14 days of storage. The thiobarbituric acid reactive
      substances and volatile basic nitrogen values were significantly lower in T1 and
      T2 than in C after 7 to 14 days of storage. The total bacterial counts were
      significantly lower in T1 and T2 than in C after 14 days of storage. In a sensory
      evaluation, tenderness and overall acceptability were significantly higher in T1
      and T2 than in C at the end of the storage period (21 days). We propose that the
      MAP method can improve beef quality characteristics of low-grade beef during cold
      storage. However, the beneficial effects did not outweigh the cost increase to
      implement MAP. 

PMID- 25049770
TI  - National genetic evaluation (system) of hanwoo (korean native cattle).
AB  - Hanwoo (Also known as Korean native cattle; Bos taurus coreanae) have been used
      for transportation and farming for a long time in South Korea. It has been about
      30 yrs since Hanwoo improvement began in earnest as beef cattle for meat yield.
      The purpose of this study was to determine the trend of improvement as well as to
      estimate genetic parameters of the traits being used for seedstock selection
      based on the data collected from the past. Hanwoo proven bulls in South Korea are
      currently selected through performance and progeny tests. National Hanwoo genetic
      evaluations are implemented with yearling weight (YW), carcass weight (CW), eye
      muscle area (EMA), backfat thickness (BF) and marbling score (MS). Yearling
      weights and MS are used for selecting young bulls, and EMA, BF, and MS are used
      for selecting proven bulls. One individual per testing room was used for
      performance tests, and five individuals per room for progeny tests. Individuals
      tested were not allowed to graze pasture, but there was enough space for them to
      move around in the testing room. Feeds including roughages and minerals were fed
      ad libitum, and concentrates were provided at the rate of about 1.8% of
      individual weight. Overall means of the traits were 352.8+/-38.56 kg, 335.09+/
      44.61 kg, 77.85+/-8.838 cm(2), 8.6+/-3.7 mm and 3.293+/-1.648 for YW, CW, EMA, BF
      and MS. Heritabilities estimated in this study were 0.30, 0.30, 0.42, 0.50 and
      0.63 in YW, CW, EMA, BF and MS, respectively, which are similar to results from
      previous research. Yearling weight was 315.54 kg in 1998, and had increased to
      355.06 kg in 2011, resulting in about 40 kg of improvement over 13 yrs. YW and CW
      have improved remarkably over the past 15 yrs. Breeding values between 1996 and
      2000 decreased or did not change much, but have moved in a desirable direction
      since 2001. These improvements correspond with the substantial increase in use of
      animal models since the late 1990s in Korea. Hanwoo testing programs have
      practically contributed to the improvement in aspects of quality and quantity. In
      sum, the current selection system is good enough to accommodate circumstances
      where fewer sires are used on many more cows. Although progeny tests take longer
      and cost more, they seem to be appropriate under the circumstances of the
      domestic market with its higher requirement for better meat quality.
      Consequently, accumulative data collection, genetic evaluation model development,
      revision of selection indices, as well as cooperation among farms, associations,
      National Agricultural Cooperative Federation, universities, research institutes,
      and government agencies must be applied to the Hanwoo selection program. All
      these efforts will assist the domestic market to secure a competitive position
      against imported beef under Free Trade Agreement trade system and will provide
      farmers with higher profits as well as the public with a higher quality of beef. 

PMID- 25049771
TI  - Phylogenetic Analysis of a Privately-owned Korean Native Chicken Population Using
      mtDNA D-loop Variations.
AB  - The use of Korean native chicken is increasing, and the discovery of new genetic
      resources is very important from both economic and genetic conservation points of
      view. In this study, mtDNA D-loop sequences from 272 privately-owned Korean
      native chickens from a Hyunin farm were investigated. Seventeen nucleotide
      substitutions were identified from the sequence analysis and they were classified
      as 6 haplotypes. Previously investigated haplotypes in five Korean native chicken
      populations have been compared with the Hyunin chicken population. The results
      indicated that two haplotypes, H10 and H15, in the Hyunin chicken population were
      not previously identified in other Korean native chicken populations,
      representing 33.09% (90/272) and 1.1% (3/272) of the Hyunin population,
      respectively. On the other hand, four other haplotypes were identical to those of
      a previous study of Korean native chicken populations. This result is indicative
      of conservation strategies of Hyunin chicken populations for expanding the
      genetic diversity in the Korean native chicken population. 

PMID- 25049772
TI  - mtDNA Diversity and Phylogenetic State of Korean Cattle Breed, Chikso.
AB  - In order to analyze the genetic diversity and phylogenetic status of the Korean
      Chikso breed, we determined sequences of mtDNA cytochrome b (cyt b) gene and
      performed phylogenetic analysis using 239 individuals from 5 Chikso populations.
      Five non-synonymous mutations of a total of 15 polymorphic sites were identified
      among 239 cyt b coding sequences. Thirteen haplotypes were defined, and haplotype
      diversity was 0.4709 ranging from 0.2577 to 0.6114. Thirty-five haplotypes (C1
      C35) were classified among 9 Asia and 3 European breeds. C2 was a major haplotype
      that contained 206 sequences (64.6%) from all breeds used. C3-C13 haplotypes were
      Chikso-specific haplotypes. C1 and C2 haplotypes contained 80.5% of cyt b
      sequences of Hanwoo, Yanbian, Zaosheng and JB breeds. In phylogenetic analyses,
      the Chikso breed was contained into B. taurus lineage and was genetically more
      closely related to two Chinese breeds than to Korean brown cattle, Hanwoo. These
      results suggest that Chikso and Hanwoo have a genetic difference based on the
      mtDNA cyt b gene as well as their coat color, sufficient for classification as a
      separate breed. 

PMID- 25049773
TI  - Post-parturient Disorders and Backfat Loss in Tropical Sows in Relation to
      Backfat Thickness before Farrowing and Postpartum Intravenous Supportive
      Treatment.
AB  - The aim of the present study was to determine the evidence of post-parturient
      disorders and backfat loss during lactation in sows raised in tropical areas in
      relation to their backfat thickness before farrowing and postpartum intravenous
      supportive treatment. Backfat thickness was measured using A-mode ultrasonography
      at farrowing and weaning (25.5+/-1.4 d) in 70 sows. The sows were divided into
      three groups according to backfat thickness before farrowing, i.e., 15.0 to 20.0
      mm (n = 21), 20.5 to 25.0 mm (n = 35), >25.0 mm (n = 14) and were categorized
      into two groups according to the postpartum supportive treatment, i.e., control
      (n = 31) and treatment (n = 39). After farrowing, the sows in treatment group
      received the same medications as in control sows. Furthermore an intravenous
      supportive treatment with amino acids and vitamins was administered in treatment
      groups. Rectal temperature and clinical signs of the sows including vaginal
      discharge, udder problems and appetite were determined at d 0, 1, 2 and 3 of
      parturition. It was found that, on average, the backfat thickness was 22.4+/-3.9
      mm at farrowing and 19.9+/-2.9 mm at weaning. The backfat loss and the relative
      backfat loss during the lactation period were 2.6 mm and 10.6%, respectively. The
      sows with a backfat of 15.0 to 20.0 mm before farrowing lost less backfat than
      those with a backfat of 20.5 to 25.0 mm and >25.0 mm (p<0.05). Sows with a
      backfat of 15.0 to 20.0 mm had a better appetite on d 1 postpartum than sows with
      a backfat of 20.5 to 25.0 mm (p = 0.020). The percentage of sows losing backfat
      >10% during lactation were higher in sows with a backfat of >25.0 mm before
      farrowing (85.7%) than sows with a backfat of 15.0 to 20.0 mm before farrowing
      (35.0%) (p = 0.008). The percentage of sows with a reduced appetite on d 1 (90.3%
      vs 71.8%, p = 0.018) and d 2 (61.3% versus 33.3%, p = 0.005) postpartum in the
      treatment group was lower than the control group. In conclusion, the backfat
      thickness of sows at farrowing influenced backfat loss during lactation under hot
      and humid climates. The intravenous supportive treatment of sows with amino acid
      and vitamins significantly improved the appetite of postpartum sows. 

PMID- 25049774
TI  - Effect of Glycosaminoglycans on In vitro Fertilizing Ability and In vitro
      Developmental Potential of Bovine Embryos.
AB  - The glycosaminoglycans (GAGs) present in the female reproductive tract promote
      sperm capacitation. When bovine sperm were exposed to 10 MUg/ml of one of four
      GAGs (Chondroitin sulfate, CS; Dermatan sulfate, DS; Hyaluronic acid, HA;
      Heparin, HP) for 5 h, the total motility (TM), straight-line velocity (VSL), and
      curvilinear velocity (VCL) were higher in the HP- or HA-treated sperm, relative
      to control and CS- or DS-treated sperm. HP and HA treatments increased the levels
      of capacitated and acrosome-reacted sperm over time, compared to other treatment
      groups (p<0.05). In addition, sperm exposed to HP or HA for 1 h before IVF
      exhibited significantly improved fertilizing ability, as assessed by 2 pronucleus
      (PN) formation and cleavage rates at d 2. Exposure to these GAGs also enhanced in
      vitro embryo development rates and embryo quality, and increased the ICM and
      total blastocyst cell numbers at d 8 after IVF (p<0.05). A real-time PCR analysis
      showed that the expression levels of pluripotency (Oct 4), cell growth (Glut 5),
      and anti-apoptosis (Bax inhibitor) genes were significantly higher in embryos
      derived from HA- or HP-treated sperm than in control or other treatment groups,
      while pro-apoptotic gene expression (caspase-3) was significantly lower in all
      GAG treatment groups (p<0.05). These results demonstrated that exposure of bovine
      sperm to HP or HA positively correlates with in vitro fertilizing ability, in
      vitro embryo developmental potential, and embryonic gene expression. 

PMID- 25049775
TI  - Effects of Lactation Stage and Individual Performance on Milk cis-9, trans-11
      Conjugated Linoleic Acids Content in Dairy Cows.
AB  - The goal of this study was to evaluate the effects of lactation stage and
      individual performance on milk cis-9, trans-11 conjugated linoleic acid (CLA)
      content in dairy cows. In experiment 1, the milk cis-9, trans-11 CLA content from
      dairy cows in early (0.33+/-0.014%), middle (0.37+/-0.010%), and late stages
      (0.44+/-0.020%) showed significant differences (p<0.05); and the individual
      contents of the major fatty acids, especially cis-9, trans-11 CLA in cows of the
      same lactation were also variable. In the second experiment design as a
      validation test, our results once again showed that the individual contents of
      cis-9, trans-11 CLA were various, and a difference of about 2-fold (0.55% vs
      0.95%) was observed, although the animals were offered same diet. These data
      demonstrated that lactation stage and individual performance have considerable
      effects on milk cis-9, trans-11 CLA contents. 

PMID- 25049776
TI  - Fermentation Quality of Ensiled Water Hyacinth (Eichhornia crassipes) as Affected
      by Additives.
AB  - A lab-scale ensiling study was carried out to investigate the fermentation
      quality of water hyacinth (WH) supplemented with molasses, rice bran, as an
      absorbent, and an inoculant in the form of fermented vegetable juice and their
      combinations. After wilting the water hyacinths for 7 h to a dry matter (DM)
      content of 240 to 250 g/kg, the following treatments were applied: i) Control
      (C), WH only; ii) WH with sugarcane molasses at 40 g/kg WH (CM); iii) WH
      inoculated with fermented vegetable juice at 10 ml/kg WH (CI); iv) CM and CI
      (CMI) combined; v) WH with 150 g rice bran/kg WH (CA); vi) CA and CI combined
      (CAI); vii) CA and CM combined (CAM); and viii) CA, CM and CI combined (CAMI).
      After application of additives, the differently treated forages were mixed and
      ensiled in triplicates in 1,500-ml polyethylene jars. After ensiling for 3 d, pH
      values in all treatments, except C and CI, had decreased to approximately 4.0 and
      remained low till 14 d. After 56 d, pH had increased between 0.4 to 0.9 pH-units
      compared to those at 14 d. The ammonia nitrogen (NH3-N) concentration ranged from
      an acceptable level in treatment CM (8 g/kg N) to a high NH3-N value in treatment
      CMI (16 g/kg N). Lactic acid formation was higher in CI than in all other
      treatments. Butyric acid contents, which indicate badly fermented silages, were
      low in all silages (<2 g/kg DM). There were two-way interactions (p-values from
      <0.001 to 0.045) for almost all fermentation end-products and pH, except for the
      molasses*inoculant interaction on NH3-N (p = 0.26). Significant 3-way
      interactions were found on all observed variables except for weight losses of
      silages. It is concluded that conserving wilted WH as silage for ruminants may be
      improved by the addition of molasses or rice bran. 

PMID- 25049777
TI  - Limiting Concentrate during Growing Period Affect Performance and Gene Expression
      of Hepatic Gluconeogenic Enzymes and Visfatin in Korean Native Beef Calves.
AB  - This study elucidated the effects of limited concentrate feeding on growth,
      plasma profile, and gene expression of gluconeogenic enzymes and visfatin in the
      liver of Hanwoo beef calves. The purpose of this study was to test that reducing
      the amount of concentrate would partially be compensated by increasing the intake
      of forage and by altering the metabolic status. The study utilized 20 Korean
      native beef calves (Hanwoo; 60 to 70 d of age) divided into two groups of 10
      calves each for 158 d. Control group calves received the amount of concentrate as
      per the established Korean feeding standards for Hanwoo, whereas calves in the
      restricted group only received half the amount of concentrate as per standard
      requirements. Good quality forage (Timothy hay) was available for ad libitum
      consumption to both groups. Since calves were with their dam until 4 months of
      age in breeding pens before weaning, the intake of milk before weaning was not
      recorded, however, the concentrate and forage intakes were recorded daily. Body
      weights (BW) were recorded at start and on 10 d interval. Blood samples were
      collected at start and at 50 d interval. On the final day of the experiment,
      liver biopsies were collected from all animals in each group. The BW was not
      different between the groups at all times, but tended to be higher (p = 0.061)
      only at final BW in control than restricted group. Total BW gain in the control
      group was 116.2 kg as opposed to 84.1 kg in restricted group that led to average
      BW gain of 736 g/d and 532 g/d in respective groups, and the differences were
      significant (p<0.01). As planned, the calves in the control group had higher
      concentrate and lower forage intake than the restricted group. The plasma
      variables like total protein and urea were higher (p<0.05) in control than
      restricted group. The mRNA expressions for the gluconeogenic enzymes such as
      cytosolic phosphoenol pyruvate carboxykinase (EC 4.1.1.32) and pyruvate
      carboxylase (EC 6.4.1.1), and visfatin measured by quantitative real-time PCR in
      liver biopsies showed higher expression (p<0.05) in restricted group than
      control. Overall, restricting concentrate severely reduced the growth intensity
      and affected few plasma indices, and gene expression in liver was increased
      indicating that restricting concentrate in the feeding schemes during early
      growth for beef calves is not advocated. 

PMID- 25049778
TI  - The Ewe's Reproductive Performance, Growth Rate and Carcass Quality of Lambs Kept
      in a Barn vs Those Kept under an Overhead Shelter.
AB  - A HERD OF POLISH LOWLAND LOCAL SHEEP WAS DIVIDED INTO TWO EQUAL GROUPS: the first
      group was kept under an overhead shelter, and the second group was kept in a warm
      barn. The effect of maintenance on ewe's reproductive performance, survival as
      well as the growth rate of lambs, and their carcasses quality was investigated.
      The lack of differences in fertility and prolificacy of ewes as well as in the
      survival and growth rate between the groups confirmed a good adaptation of
      Zelaznienska sheep to low temperature. Harsh environmental conditions did not
      cause a significant decrease of the body weight growth; however, they brought in
      an (insignificant) reduction of subcutaneous fat thickness and meatiness of the
      loin part of a lamb's body. The fat content of carcasses obtained from lambs
      reared under the overhead shelter was significantly lower, with no differences of
      meat and bones contribution between the groups. 

PMID- 25049779
TI  - Diets based on sugar cane treated with calcium oxide for lambs.
AB  - This experiment was conducted to evaluate the intake, nutrient apparent
      digestibility and the effect of total collection days (two and four days) on
      apparent digestibility estimates for lambs fed diets containing sugar cane
      treated with calcium oxide (CaO). Eight Santa Ines castrated male lambs with a
      16.6+/-1.8 kg body weight were used. The lambs were distributed in two 4*4 Latin
      squares, with four experimental periods of 14 d each. The animals were kept in
      1.2 m(2) individual pens, and the intake and digestibility evaluations were
      performed during the last four days of each period. The diets were formulated to
      be isonitrogenous, containing 14% crude protein (CP), and presenting 70% sugar
      cane treated with 0, 0.75, 1.5 or 2.25% of CaO (as-fed basis), corrected with 1%
      urea, and 30% concentrate. The sugar cane with added CaO was chopped, treated,
      and offered to the animals after 24 h of storage. The sugar cane with CaO
      increased the DM, OM, CP, NDF, NDFap, TC, NFCap and TDN intake (kg/d), when
      compared to natural sugar cane, and produced the same intake expressed as a
      percentage of body weight (% BW). The NFCap digestibility of the CaO-treated
      sugar cane was inferior to the NFCap digestibility in natural sugar cane. There
      was a linear increase in the DM intake with the CaO-added sugar cane, but the DM
      and NDF digestibility and the TDN content decreased linearly. The chemical
      treatment of sugar cane with CaO increases the intake but does not improve the
      nutrient digestibility. Two days of total fecal collection were found to be
      sufficient to estimate the total apparent digestibility in lambs. 

PMID- 25049780
TI  - Effect of high phytase inclusion rates on performance of broilers fed diets not
      severely limited in available phosphorus.
AB  - Phytate is not only an unavailable source of phosphorus (P) for broilers but it
      also acts as an anti-nutrient, reducing protein and mineral absorption,
      increasing endogenous losses and reducing broiler performance. The objective of
      this study was to investigate the anti-nutritional effects of phytate by
      including high levels of phytase in diets not severely limited in available P. A
      total of 768 male Arbor Acres broilers were distributed in six treatments of
      eight replicate pens of 16 birds each consisting of a positive control diet (PC),
      positive control with 500 FTU/kg phytase, negative control (NC) diet with lower
      available P and calcium (Ca) levels and the same NC diet with 500, 1,000 or 1,500
      FTU/kg phytase. Body weight gain (BWG), feed intake (FI), feed conversion ratio
      (FCR) and mortality were determined at 21 and 35 d of age while foot ash was
      determined in four birds per pen at 21 d of age. FI, FCR and foot ash where not
      affected by the lower mineral diets at 21 d of age nor by the enzyme inclusion
      but broilers fed lower Ca and available P diets had lower BWG. At 35 d of age no
      difference was observed between broilers fed the positive or NC diets but
      broilers fed 500, 1,000 and 1,500 FTU/kg on top of the NC diet had better FCR
      than broilers fed the positive control diet. When compared to birds fed a diet
      adequate in P, birds fed the same diet included with 500, 1,000 and 1,500 FTU/kg
      of phytase in marginally deficient available P and Ca diets had an improvement of
      performance. These results support the concept that hydrolysing phytate and
      reducing the anti-nutritional effects of phytate improves bird performance on
      marginally deficient diets that were not covering the P requirement of birds. 

PMID- 25049781
TI  - Effects of Dietary L-carnitine Supplementation on Growth Performance, Organ
      Weight, Biochemical Parameters and Ascites Susceptibility in Broilers Reared
      Under Low-temperature Environment.
AB  - The objective of this study was to investigate the effects of L-carnitine on
      growth performance, organ weight, biochemical parameters of blood, heart and
      liver, and ascites susceptibility of broilers at different ages reared under a
      low-temperature environment. A total of 420 1-d-old male Ross 308 broilers were
      randomly assigned to two dietary treatments with fifteen replicates of fourteen
      broilers each. Treatment diets consisted of L-carnitine supplementation at levels
      of 0 and 100 mg/kg. At 11-d of age, low temperature stress was used to increase
      ascites susceptibility. Blood, heart and liver samples were collected at
      different ages for analysis of boichemical parameters. The results showed that,
      there was no significant difference in growth performance with L-carnitine
      supplementation, but the mortality due to ascites was significantly decreased.
      Dietary L-carnitine supplementation significantly reduced heart index (HI) and
      ascites heart index (AHI) on d 21, lung index (LUI) on d 35 and liver index (LI)
      on d 42. The broilers fed diets containing L-carnitine had significantly lower
      red blood cell counts (RBC), hemoglobin (HGB) concentration and hematocrit (HCT)
      on d 42. Dietary L-carnitine supplementation significantly reduced
      malondialdehyde (MDA) content of heart tissue on d 21 and 35, and significantly
      increased total superoxide dismutase (T-SOD) and Glutathione peroxidase (GSH-Px)
      activity of the heart on d 21 and 42. L-carnitine supplementation significantly
      reduced serum triglyceride (TG) content on d 28 and 35 and serum glucose (GLU) on
      d 35 and 42, and significantly increased serum total protein (TP) and globulin
      (GLO) content on d 42. L-carnitine supplementation significantly enhanced liver
      succinodehydrogenase (SDH), malic dehydrogenase (MDH) and Na(+)-K(+)-ATPase
      activity on d 28, and tended to reduce the lactic acid (LD) level of liver on d
      35 (p = 0.06). L-carnitine supplementation significantly reduced serum uric acid
      (UA) content on d 28, 35 and 42. Based on the current results, it can be
      concluded that dietary L-carnitine supplementation reduced organ index, red blood
      cell counts and hematocrit, enhanced antioxidative capacity of the heart,
      enhanced liver enzymes activity involved in tricarboxylic acid cycle, and reduced
      serum glucose and triglyceride. Therefore, it is suggested that L-carnitine can
      potentially reduce susceptibility and mortality due to ascites. 

PMID- 25049782
TI  - Effect of vitamin levels and different stocking densities on performance,
      nutrient digestibility, and blood characteristics of growing pigs.
AB  - This study was conducted to evaluate the effects of dietary vitamin levels and
      stocking densities on growth performance, nutrient digestibility, and blood
      characteristics in growing pigs. A 2*3 factorial (two vitamin levels, three
      regimens of stocking densities) arrangement was utilized with 96 pigs (23.10*0.95
      kg initial body weight and 63 d of age) for 36 d. The pigs were allocated to pens
      with different stocking density (0.64, 0.48, and 0.38 m(2)/pig, respectively).
      The diets used in this study were a normal diet (based on NRC) and a high level
      of vitamin diet (2-fold higher than normal diet). The ADG and ADFI of pigs were
      decreased as the stocking density increased (p = 0.03 and p = 0.01,
      respectively). The G/F of pigs was 5% lower in the high vitamin treatment (p =
      0.03) as compared with the control treatment. The apparent total tract
      digestibility (ATTD) of DM and N digestibility was negatively affected by the
      high level of vitamin in diets (p = 0.05 and p = 0.04, respectively). Moreover, a
      significant and negative effect on the ATTD of N was detected in the large groups
      (linear, p = 0.02). Blood cortisol concentration was increased with increasing
      stocking density (linear, p = 0.05), and was decreased by high level of vitamin
      (p = 0.04) at the end of this experiment. Stocking density also caused a linear
      reduction in WBC concentration (p = 0.05). Our data indicated that the principal
      effect of stocking density was not reliant on dietary vitamin levels. In
      conclusion, results indicated that doubling the vitamin supplementation did not
      improve the growth performance of pigs in high density. However, the blood
      cortisol concentration was decreased but the ATTD of N digestibility was impaired
      by high level of vitamin diet. 

PMID- 25049783
TI  - Effect of supplementing organic selenium on performance, carcass traits,
      oxidative parameters and immune responses in commercial broiler chickens.
AB  - An experiment was conducted to determine the effect of supplementing various
      concentrations (0, 100, 200, 300, or 400 MUg/kg diet) of organic Se on growth
      performance, carcass traits, oxidative stress, and immune responses in commercial
      broiler chickens reared in open-sided poultry house under tropical climatic
      conditions. Each diet was fed ad libitum to eight replicates consisting of six
      birds in each pen from 1 to 42 d of age. Body weight gain and feed efficiency,
      and relative weight of liver, abdominal fat and ready to cook yields were not
      affected (p>0.05) by organic Se supplementation to broiler diets. Lipid
      peroxidation in plasma decreased, while activities of glutathione peroxidase and
      glutathione reductase in plasma increased (p<0.01) linearly with Se concentration
      in diet. The ratios between heterophyls and lymphocytes and relative weight of
      lymphoid organs (bursa, spleen, and thymus), and antibody production to Newcastle
      disease vaccination were not affected (p>0.05) by Se supplementation to broiler
      diets. However, the cell-mediated immunity (lymphocyte proliferation ratio)
      increased (p<0.01) linearly with dietary Se concentration. The results of the
      present study indicate that the supplementation of Se did not influence body
      weight and feed efficiency. However, supplementation of Se increased antioxidant
      status and lymphocyte proliferation in broiler chickens. 

PMID- 25049784
TI  - Effects of Enzyme Complex Supplementation to a Paddy-based Diet on Performance
      and Nutrient Digestibility of Meat-type Ducks.
AB  - Paddy rice is rarely used as a feed because of its high fiber content. In this
      study, two experiments were conducted to study the effects of supplementing an
      enzyme complex consisting of xylanase, beta-glucanase and cellulase, to paddy
      based diets on the performance and nutrient digestibility in meat-type ducks. In
      the both experiments, meat-type ducks (Cherry Valley) were randomly assigned to
      four treatments. Treatment 1 was a basal diet of corn-soybean; treatment 2 was a
      basal diet of corn-paddy-soybean; treatment 3, had enzyme complex added to the
      corn-paddy-soybean basal diet at levels of 0.5 g/kg diet; and treatment 4, had
      enzyme complex added to the corn-paddy-soybean diet at levels of 1.0 g/kg diet.
      The results showed that the enzyme complex increased the ADG, and decreased the
      ADFI and F/G significantly (p<0.05) in the ducks, and the ADFI for the ducks fed
      the corn-paddy-soybean diet showed no difference compared to the ducks fed corn
      soybean diets at all stages of the experiment (p<0.05). When corn was partially
      replaced by paddy, the digestibility of CP and NDF was decreased and increased,
      respectively (p<0.05), and the level of enzyme complex had a significant effect
      on both CP and NDF digestibility (p<0.05). As for the AME, addition of enzyme
      complex increased it significantly (p<0.05), but both diet types and levels of
      enzyme complex had no effect (p>0.05). The outcome of this research indicates
      that the application of enzyme complex made up of xylanase, beta-glucanase, and
      cellulase, in the corn-paddy-soybean diet, can improve performance and nutrition
      digestibility in meat-type ducks. 

PMID- 25049785
TI  - Effects of dietary persimmon peel and its ethanol extract on the production
      performance and liver lipids in the late stage of egg production in laying hens.
AB  - The purpose of this study was to investigate the dietary effects of persimmon
      peel (PP) and PP ethanol extract (PPE) on egg production, egg quality, and liver
      lipids in the late stage of egg production in laying hens. One hundred and twenty
      50-wk-old Hy-Line Brown layers (n = 120) were fed different diets. Four replicate
      groups of 6 hens each were randomly assigned to 5 dietary treatments. The 5
      dietary treatments were as follows: i) CON, basal diet; ii) PP 0.15, CON+0.15% PP
      (0.035% tannin); iii) PP 0.5, CON +0.5% PP (0.117% tannin); iv) PPE 0.075,
      CON+0.075% PPE (0.03% tannin); and v) PPE 0.25, CON+0.25% PPE (0.11% tannin). The
      total tannin concentration of PPE was higher (p<0.05) than that of PP. Egg
      production in the PP 0.5 group was higher than in the other groups. Egg
      production and mass of hens in the PPE 0.25 group showed a greater decrease than
      that in the other groups (p<0.05). Eggshell color in the PP 0.15, PP 0.5, and PPE
      0.075 groups was lighter than that of the control group (p<0.05). The Haugh unit
      for the groups that were fed PP and PPE were significantly higher than that in
      the other groups after 7 d of storage (p<0.05). Therefore, PP seems an effective
      feed additive for improving the production performance and egg quality in late
      stage laying hens. 

PMID- 25049786
TI  - Effect of Phytogenic Feed Additives in Soybean Meal on In vitro Swine
      Fermentation for Odor Reduction and Bacterial Community Comparison.
AB  - The effect of different phytogenic feed additives on reducing odorous compounds
      in swine was investigated using in vitro fermentation and analyzed their
      microbial communities. Soybean meal (1%) added with 0.1% different phytogenic
      feed additives (FA) were in vitro fermented using swine fecal slurries and
      anaerobically incubated for 12 and 24 h. The phytogenic FAs used were red ginseng
      barn powder (Panax ginseng C. A. Meyer, FA1), persimmon leaf powder (Diospyros
      virginiana L., FA2), ginkgo leaf powder (Ginkgo biloba L., FA3), and oregano
      lippia seed oil extract (Lippia graveolens Kunth, OL, FA4). Total gas production,
      pH, ammonia-nitrogen (NH3-N), hydrogen sulfide (H2S), nitrite-nitrogen (NO2 (-)
      N), nitrate-nitrogen (NO3 (-)-N), sulfate (SO4 (--)), volatile fatty acids (VFA)
      and other metabolites concentration were determined. Microbial communities were
      also analyzed using 16S rRNA DGGE. Results showed that the pH values on all
      treatments increased as incubation time became longer except for FA4 where it
      decreased. Moreover, FA4 incubated for 12 and 24 h was not detected in NH3-N and
      H2S. Addition of FAs decreased (p<0.05) propionate production but increased
      (p<0.05) the total VFA production. Ten 16S rRNA DGGE bands were identified which
      ranged from 96 to 100% identity which were mostly isolated from the intestine.
      Similarity index showed three clearly different clusters: I (FA2 and FA3), II
      (Con and FA1), and III (FA4). Dominant bands which were identified closest to
      Eubacterium limosum (ATCC 8486T), Uncultured bacterium clone PF6641 and
      Streptococcus lutetiensis (CIP 106849T) were present only in the FA4 treatment
      group and were not found in other groups. FA4 had a different bacterial diversity
      compared to control and other treatments and thus explains having lowest odorous
      compounds. Addition of FA4 to an enriched protein feed source for growing swine
      may effectively reduce odorous compounds which are typically associated with
      swine production. 

PMID- 25049788
TI  - Effects of Electrical Stimulation on Lipid Oxidation and Warmed-over Flavor of
      Precooked Roast Beef.
AB  - Many manufacturing processes damage the structure of meat products and this often
      contributes to lipid oxidation which could influence warmed-over flavor (WOF) in
      precooked beef that is reheated beef. Electrical stimulation causes contraction
      of muscles and improves tissue tenderization. The purpose of this study was to
      evaluate the rate of lipid oxidation or warmed-over flavor that could be affected
      by electrical stimulation of precooked roast beef after refrigerated storage and
      reheating. The results show that there was no significant difference between
      chemical compositions and cooking yields when comparing non-electrically
      stimulated and electrically stimulated roast beef. Moreover, electrical
      stimulation had no significant effect on oxidative stability and off-flavor
      problems of precooked roast beef as evaluated by thiobarbituric acid reactive
      substances (TBARS) and sensory test (warmed-over aroma and warmed-over flavor).
      However, there was an increased undesirable WOF and a decrease in tenderness for
      both ES and Non-ES treatments over refrigerated storage time. Electrical
      stimulation did cause reactions of amino acids or other compounds to decrease the
      desirable beef flavor in re-cooked meat. 

PMID- 25049787
TI  - The effect of slaughter season on the Fatty Acid profile in four types of fat
      deposits in crossbred beef bulls.
AB  - The objective of this study was to determine the effect of slaughter season on
      the fatty acid profile in four types of fat deposits in crossbred (Polish
      Holstein Friesian Black-and-White*Limousine) beef bulls. The percentage share of
      fatty acids was determined by gas chromatography and were divided into the
      following categories of fatty acids: saturated (SFAs), unsaturated (UFAs),
      monounsaturated (MUFAs), polyunsaturated (PUFAs), desirable hypocholesterolemic
      (DFAs) and undesirable hypercholesterolemic (OFAs), n-3 and n-6. Perinephric fat
      was characterized by the highest SFA concentrations (59.89%), and subcutaneous
      fat had the highest MUFA content (50.63%). Intramuscular fat was marked by a high
      percentage share of PUFAs and the highest PUFA/SFA ratio. The slaughter season
      had a significant effect on the levels of C18:3, C20:4 (p<=0.01) and conjugated
      linoleic acid (p<=0.05). There was an interaction between the slaughter season
      and fat type for the content of C20:4 (p<=0.01) and C20:5 (p<=0.05). The results
      of this study show that beef from cattle slaughtered in the summer season has a
      higher nutritional value and more health-promoting properties. 

PMID- 25049789
TI  - Antioxidant Activities of Achyranthes japonica Nakai Extract and Its Application
      to the Pork Sausages.
AB  - Influence of Achyranthes japonica Nakai Extract (AJNE) on properties of pork
      sausages were studied in the present investigation. AJNE was added to sausages
      alone or in combination with ascorbic acid to obtain a comparative analysis on
      properties of control and ascorbic acid added-sausages. Results showed that
      addition of 0.05% AJNE led to a decrease in color L* and whiteness (W), and an
      increase in color b* of pork sausage samples (p<0.05). Although color a* of pork
      sausages containing AJNE was not significantly different, ascorbic acid added
      sausages were highest amongst other treatments (p<0.05). Sausages containing AJNE
      had lower non-heme iron values and peroxide value (POV) than control sausages
      (p<0.05); however, high nitrosomyoglobin content was observed in AJNE added
      sausages (p<0.05). Ascorbic acid led to a decrease in residual nitrite
      concentration of sausages (p<0.05), but no difference was found in AJNE added
      sausages. Free radical scavenging analysis showed that AJNE did not affect 1,1
      diphenyl -2-picrylhydrazyl (DPPH) activity of sausages, whereas ascorbic acid
      added-sausages showed relatively higher activity among the samples (p<0.05).
      Addition of AJNE had no influence on texture properties of sausages. In sensory
      evaluation, AJNE treatment had significant effects on color (p<0.05), but no
      significant effects on aroma, flavor, springiness, juiciness, and overall
      acceptability. In conclusion, the addition of AJNE, as a natural supplement may
      offer natural antioxidants for pork sausages, and appears to be particularly
      effective in inducing changes in non-heme iron concentration, POV value and
      nitrosomyglobin content. 

PMID- 25049790
TI  - Chemical composition and meat quality attributes of indigenous sheep and goats
      from traditional production system in Tanzania.
AB  - The aim of the study was to compare chemical composition and quality attributes
      of meat between male long fat tailed sheep (n = 17) and Small East African goats
      (n = 17) existing in Tanzania. Animals of 1.5 to 2 yrs in age and live body
      weight of 22.59+/-0.50 kg were purchased from livestock auction markets. Animals
      were fasted for 18 h and slaughtered according to standard halal procedure. Left
      carcasses were dissected into muscles, fat and bone and the muscle and fat were
      mixed together and chemically analysed. Meat quality attributes were measured
      based on Muscle longissimus thoracis et lumborum excised from right sides of
      carcasses. Goat carcasses had significant higher (p = 0.0302) moisture content
      (70.65% vs 66.96%) and lower (p = 0.0027) ether extract (2.49% vs 5.82%) than
      sheep but there was no significant species differences in protein and ash
      content. Sheep had lower (p = 0.0157) ultimate pH (5.74 vs 5.88) and higher (p =
      0.0307) temperature (3.77 degrees C vs 3.15 degrees C) than goat carcasses. Sheep
      meat had lower (p = 0.0021) shear force values (29.83 N vs 34.07 N) than goat.
      Within species, at day 9 of ageing, meat tenderness improved (p = 0.0001) by
      44.63% and 34.18% for sheep and goat. Pooled data showed that at d 9 of ageing,
      meat tenderness improved (p = 0.0001) by 39.25% (from 39.54 N to 24.02 N)
      compared to tenderness of meat which was not aged at day one of slaughter. The
      present study demonstrated the differences in chemical composition and quality
      attributes of meat existing between sheep and goats originated from East Africa. 

PMID- 25049791
TI  - Subfertility problems leading to disposal of breeding bulls.
AB  - Subfertility problems are encountered frequently in the cattle and buffalo bulls
      commercially maintained for semen production in dairy farms and under field
      conditions for natural insemination. Reports are scarce on the incidence of
      subfertility in breeding bulls, especially in India. The objective of the present
      study was to assess the incidence of the male reproductive anomalies leading to
      disposal of bovine bulls at GADVASU dairy farm, Ludhiana, Punjab (India). Data on
      frequency of various subfertility and disposal pattern of bulls maintained at the
      dairy farm, GADVASU, were collected for 12 yrs (1999 to 2010) and compiled from
      different record registers. Percentage of bulls that produced freezable semen
      (out of reserved ones) was less in cattle (25.641%) as compared to that of
      buffalo (30.4%). Various subfertility traits like poor libido and unacceptable
      seminal profile were found to be the significant reasons (p<0.01) for culling of
      the breeding bulls. Inadequate sex drive and poor semen quality were the main
      contributing factors for bull disposal in cattle whereas poor semen freezability
      was most frequently observed in buffalo bulls. All the male reproductive traits
      were significantly different (p<0.05) for the periods of birth, except for semen
      volume, initial motility (IM), age at last semen collection (ALSC) and age at
      disposal. The ages at first and last semen collection as well as freezing (i.e.
      AFSC, ALSC and AFSF, ALSF, respectively) and age at disposal (AD) were higher in
      buffalo. The spermatological parameters and semen production period (SPP) were
      higher in cattle. The age at first semen donation and breeding period could be
      reduced by introducing the bulls to training at an early age. The results
      revealed an increasing trend in individual motility (IM) while semen volume,
      AFSC, AFSF, AD, FSPP, SPP, ALSC and ALSF showed a decreasing, however, not a
      definite trend, over the periods. The semen donation traits like, AFSF, of the
      cattle and buffalo bulls could be predicted from the AFSC, using prediction
      equation derived in the present study. 

PMID- 25049792
TI  - Identification and Function Prediction of Novel MicroRNAs in Laoshan Dairy Goats.
AB  - MicroRNAs are a class of endogenous small RNAs that play important roles in post
      transcriptional gene regulation by directing degradation of mRNAs or facilitating
      repression of target gene translation. In this study, three small RNA cDNA
      libraries from the mammary gland tissues of Laoshan dairy goats (Capra hircus)
      were constructed and sequenced, individually. Through Solexa high-throughput
      sequencing and bioinformatics analysis, we obtained 50 presumptive novel miRNAs
      candidates, and 55,448 putative target genes were predicted. GO annotations and
      KEGG pathway analyses showed the majority of target genes were involved in
      various biological processes and metabolic pathways. Our results discovered more
      information about the regulation network between miRNAs and mRNAs and paved a
      foundation for the molecular genetics of mammary gland development in goats. 

PMID- 25049793
TI  - Discrimination of korean native chicken lines using fifteen selected
      microsatellite markers.
AB  - In order to evaluate the genetic diversity and discrimination among five Korean
      native chicken lines, a total of 86 individuals were genotyped using 150
      microsatellite (MS) markers, and 15 highly polymorphic MS markers were selected.
      Based on the highest value of the number of alleles, the expected heterozygosity
      (He) and polymorphic information content (PIC) for the selected markers ranged
      from 6 to 12, 0.466 to 0.852, 0.709 to 0.882 and 0.648 to 0.865, respectively.
      Using these markers, the calculated genetic distance (Fst), the heterozygote
      deficit among chicken lines (Fit) and the heterozygote deficit within chicken
      line (Fis) values ranged from 0.0309 to 0.2473, 0.0013 to 0.4513 and -0.1002 to
      0.271, respectively. The expected probability of identity values in random
      individuals (PI), random half-sib (PI half-sibs ) and random sibs (PI sibs ) were
      estimated at 7.98*10(-29), 2.88*10(-20) and 1.25*10(-08), respectively,
      indicating that these markers can be used for traceability systems in Korean
      native chickens. The unrooted phylogenetic neighbor-joining (NJ) tree was
      constructed using 15 MS markers that clearly differentiated among the five native
      chicken lines. Also, the structure was estimated by the individual clustering
      with the K value of 5. The selected 15 MS markers were found to be useful for the
      conservation, breeding plan, and traceability system in Korean native chickens. 

PMID- 25049794
TI  - Analysis of Geographic and Pairwise Distances among Chinese Cashmere Goat
      Populations.
AB  - This study investigated the geographic and pairwise distances of nine Chinese
      local Cashmere goat populations through the analysis of 20 microsatellite DNA
      markers. Fluorescence PCR was used to identify the markers, which were selected
      based on their significance as identified by the Food and Agriculture
      Organization of the United Nations (FAO) and the International Society for Animal
      Genetics (ISAG). In total, 206 alleles were detected; the average allele number
      was 10.30; the polymorphism information content of loci ranged from 0.5213 to
      0.7582; the number of effective alleles ranged from 4.0484 to 4.6178; the
      observed heterozygosity was from 0.5023 to 0.5602 for the practical sample; the
      expected heterozygosity ranged from 0.5783 to 0.6464; and Allelic richness ranged
      from 4.7551 to 8.0693. These results indicated that Chinese Cashmere goat
      populations exhibited rich genetic diversity. Further, the Wright's F-statistics
      of subpopulation within total (FST) was 0.1184; the genetic differentiation
      coefficient (GST) was 0.0940; and the average gene flow (Nm) was 2.0415. All
      pairwise FST values among the populations were highly significant (p<0.01 or
      p<0.001), suggesting that the populations studied should all be considered to be
      separate breeds. Finally, the clustering analysis divided the Chinese Cashmere
      goat populations into at least four clusters, with the Hexi and Yashan goat
      populations alone in one cluster. These results have provided useful, practical,
      and important information for the future of Chinese Cashmere goat breeding. 

PMID- 25049795
TI  - Effects of hormones on the expression of matrix metalloproteinases and their
      inhibitors in bovine spermatozoa.
AB  - Proteases and protease inhibitors play key roles in most physiological processes,
      including cell migration, cell signaling, and cell surface and tissue remodeling.
      Among these, the matrix metalloproteinase (MMPs) pathway is one of the most
      efficient biosynthetic pathways for controlling the activation of enzymes
      responsible for protein degradation. This also indicates the association of MMPs
      with the maturation of spermatozoa. In an attempt to investigate the effect of
      MMP activation and inhibitors in cultures with various hormones during sperm
      capacitation, we examined and monitored the localization and expression of MMPs
      (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-2 and TIMP-3),
      as well as their expression profiles. Matured spermatozoa were collected from
      cultures with follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
      Lutalyse at 1 h, 6 h, 18 h, and 24 h. ELISA detected the expression of MMP-2, MMP
      9, TIMP-2, and TIMP-3 in all culture media, regardless of medium type (FSH
      supplemented fertilization Brackett-Oliphant medium (FFBO), LH-supplemented FBO
      (LFBO), or Lutalyse-supplemented FBO (LuFBO)). TIMP-2 and TIMP-3 expression
      patterns decreased in LFBO and LuFBO. MMP-2 and MMP-9 activity in FBO and FFBO
      progressively increased from 1 h to 24 h but was not detected in LFBO and LuFBO.
      The localization and expression of TIMP-2 and TIMP-3 in sperm heads was also
      measured by immunofluorescence analysis. However, MMPs were not detected in the
      sperm heads. MMP and TIMP expression patterns differed according to the effect of
      various hormones. These findings suggest that MMPs have a role in sperm viability
      during capacitation. In conjunction with hormones, MMPs play a role in
      maintaining capacitation and fertilization by controlling extracellular matrix
      inhibitors of sperm. 

PMID- 25049796
TI  - T Cells Development Is Different between Thymus from Normal and Intrauterine
      Growth Restricted Pig Fetus at Different Gestational Stage.
AB  - This experiment was conducted to evaluate the development of T cells in
      intrauterine growth retarded (IUGR) piglets at different gestational stages, and
      tentatively explore the relationship between T cells development and the Notch
      signaling pathway. A total of 18 crossbred (Landrace*Large white) primiparous
      sows were mated at similar weights and estruses and euthanized at d 60, 90 and
      110 of gestation with six replicates for each time point. One IUGR and one normal
      fetus were picked from each litter. The T-cell subsets, mRNA expression of Delta
      like1, Delta-like4, Jagged1, and Notch2 genes in the thymus were investigated.
      Compared to normal piglets, CD3(+)CD4(-)CD8(+) cells in IUGR fetuses at d 90 was
      0.13% lower (p<0.05). At d 110 of gestation CD8(+) T cells in IUGR fetuses was
      0.19% lower (p<0.05). The percentage of CD8(+) T cells was 3.14% lower (p<0.05)
      of the total T cells in IUGR pigs at d 60. The abundance of Notch2 and Delta
      like4 mRNA at d 110 was 20.93% higher and 0.77% (p<0.05) lower, and Delta-like1
      mRNA at d 90 was 0.19% (p<0.05) higher compared to normal pigs. These results
      suggested that normal fetuses had a greater proportion of T-cell subsets at
      earlier gestation periods, and the Notch signaling pathway was likely partially
      responsible for these differences to some degree. 

PMID- 25049797
TI  - Intake and Performance of Yearling Steers Grazing Guineagrass (Panicum maximum
      cv. Tanzania) Pasture Supplemented with Different Energy Sources.
AB  - The aim of this study was to evaluate the efficiency of supplements containing
      different energy sources in relation to mineral supplementation of steers grazing
      guineagrass (Panicum maximum cv Tanzania) pasture, during the dry season. The
      experimental design was a randomized block with three treatments and four
      replications. The treatments consisted of a mineral supplementation and two other
      supplements, one based on corn seed and the other based on soybean hulls, and
      provided at 0.8% of body weight. Forty-eight, 12 month-old crossbred steers with
      an average initial body weight of 267 kg, were assigned to twelve paddocks (1,125
      ha) of guineagrass. The animals that were fed with soybean hulls and corn seed
      presented a greater average daily gain (0.982 and 0.937) when compared with the
      mineral supplementation. Soybean hulls can be used as a satisfactory food source,
      replacing corn as an energy source in the supplementation of beef cattle without
      compromising animal performance. 

PMID- 25049798
TI  - Effects of synchronicity of carbohydrate and protein degradation on rumen
      fermentation characteristics and microbial protein synthesis.
AB  - A series of in vitro studies were carried out to determine i) the effects of
      enzyme and formaldehyde treatment on the degradation characteristics of
      carbohydrate and protein sources and on the synchronicity of these processes, and
      ii) the effects of synchronizing carbohydrate and protein supply on rumen
      fermentation and microbial protein synthesis (MPS) in in vitro experiments.
      Untreated corn (C) and enzyme-treated corn (EC) were combined with soy bean meal
      with (ES) and without (S) enzyme treatment or formaldehyde treatment (FS). Six
      experimental feeds (CS, CES, CFS, ECS, ECES and ECFS) with different synchrony
      indices were prepared. Highly synchronous diets had the greatest dry matter (DM)
      digestibility when untreated corn was used. However, the degree of synchronicity
      did not influence DM digestibility when EC was mixed with various soybean meals.
      At time points of 12 h and 24 h of incubation, EC-containing diets showed lower
      ammonia-N concentrations than those of C-containing diets, irrespective of the
      degree of synchronicity, indicating that more efficient utilization of ammonia-N
      for MPS was achieved by ruminal microorganisms when EC was offered as a
      carbohydrate source. Within C-containing treatments, the purine base
      concentration increased as the diets were more synchronized. This effect was not
      observed when EC was offered. There were significant effects on VFA concentration
      of both C and S treatments and their interactions. Similar to purine
      concentrations, total VFA production and individual VFA concentration in the
      groups containing EC as an energy source was higher than those of other groups
      (CS, CES and CFS). The results of the present study suggested that the
      availability of energy or the protein source are the most limiting factors for
      rumen fermentation and MPS, rather than the degree of synchronicity. 

PMID- 25049799
TI  - Nutritive Value of Grasses in Semi-arid Rangelands of Ethiopia: Local Experience
      Based Herbage Preference Evaluation versus Laboratory Analysis.
AB  - We examined the nutritive value of common grass species in the semi-arid
      rangelands of Borana in southern Ethiopia using local experience based herbage
      preference (LEBHP) perception and laboratory techniques. Local pastoralists in
      the study area were asked to identify common grass species and rank them
      according to the species' preferences and palatability to cattle. The
      pastoralists listed a total of 15 common grass species which were then sampled
      during the main rain and cold dry seasons and analyzed for crude protein (CP),
      Neutral Detergent Fiber (NDF), Acid Detergent Fiber (ADF) and ash content to
      verify pastoralists' claim regarding the quality of individual species. The
      relative feed value (RFV) and dry matter digestibility (DMD) were also calculated
      using NDF and ADF contents. Spearman's rank correlation was used to examine
      possible relationships between laboratory results and pastoralists' experience on
      grass quality. Cenchrus ciliaris, Chrysopogon aucheri, Digitaria milanjiana,
      Eragrostis papposa and Panicum maximum were the top five species based on LEBHP
      perception. There were indications of inconsistency in terms of LEBHP perception
      among the different pastoral communities. The chemical composition of all grass
      species showed significant (p<0.05) variation between sites, seasons and species.
      The results showed that the CP values for the Borana rangelands were in the range
      of 8.7% in the main rain season to 5.1% for the cold dry season. The fiber
      constituents were relatively low in the main rain season compared to the cold dry
      season. Overall, Digitaria milanjiana had the highest CP (16.5%) content, while
      the least was recorded with Heteropogon contortus (10.8) and Aristida adoensis
      (9.8%) during the main rain season. It seems that the spatial variability of
      landscapes within the wider geographical regions, soil properties and texture,
      and land-use patterns probably contributed to site differences in species
      quality. Generally, the RFV of individual grass species was significantly
      (p<0.05) varied between and within sites. The ranking of species by pastoralists
      according to their preferences by cattle was highly correlated with the chemical
      composition of laboratory results of individual grass species with 'r' values for
      CP (0.94), ash (0.95), NDF (-0.98), ADF (-0.93) and ADL (-0.93). We suggest the
      complimentary use of LEBHP and laboratory techniques in evaluating the nutritive
      quality of rangeland forage species for sustainable animal production. 

PMID- 25049800
TI  - The effect of variety and growing conditions on the chemical composition and
      nutritive value of wheat for broilers.
AB  - The aim of this study was to examine the effect of variety and growing conditions
      of wheat on broiler performance and nutrient digestibility. One hundred and sixty
      four wheat samples, collected from a wide range of different sources, locations,
      varieties and years, were analyzed for a range of chemical and physical
      parameters. Chemical and physical parameters measured included specific weight,
      thousand grain weight (TG), in vitro viscosity, gross energy, N, NDF, starch,
      total and soluble non-starch polysaccharides (NSP), lysine, threonine, amylose,
      hardness, rate of starch digestion and protein profiles. Ninety-four of the wheat
      samples were selected for inclusion in four bird trials. Birds were housed in
      individual wire metabolizm cages from 7 to 28 d and offered water and feed ad
      libitum. Dry matter intake (DMI), live weight gain (LWG) and gain:feed were
      determined weekly. A balance collection was carried out from 14 to 21 d for
      determination of apparent metabolizable energy (AME), ME:gain, DM retention, oil
      and NDF digestibility. At 28 d the birds were sacrificed, the contents of the
      jejunum removed for determination of in vivo viscosity and the contents of the
      ileum removed for determination of ileal DM, starch and protein digestibility.
      The wheat samples used in the study had wide-ranging chemical and physical
      parameters, leading to bird DMI, LWG, gain:feed, ME:GE, AME content and ileal
      starch and protein digestibility being significantly (p<0.05) affected by wheat
      sample. A high level of N fertilizer application to the English and NI wheat
      samples tended to benefit bird performance, with increases of up to 3.4, 7.2 and
      3.8% in DMI, LWG and gain:feed, respectively. Fungicide application also appeared
      to have a positive effect on bird performance, with fungicide treated (+F) wheat
      increasing bird DMI, LWG and gain:feed by 6.6, 9.3 and 2.7%, over the non
      fungicide treated (-F) wheats. An increase (p<0.1) of 9.3% in gain:feed was also
      observed at the low seed rate of 40 compared to 640 seeds/m(2). It was concluded
      that the type of wheat sample and environmental growing conditions significantly
      affects bird performance when fed wheat-based diets. 

PMID- 25049801
TI  - Evaluation of Anti-SE Bacteriophage as Feed Additives to Prevent Salmonella
      enteritidis (SE) in Broiler.
AB  - This experiment was conducted to evaluate anti-Salmonella enteritidis (anti-SE)
      bacteriophage as feed additives to prevent Salmonella enteritidis in broilers.
      The experimental diets were formulated for 2 phases feeding trial, and 3
      different levels (0.05, 0.1 and 0.2%) of anti-SE bacteriophage were supplemented
      in basal diet. The basal diet was regarded as the control treatment. A total of
      320 1-d-old male broilers (Ross 308) were allotted by randomized complete block
      (RCB) design in 8 replicates with 10 chicks per pen. All birds were raised on
      rice hull bedding in ambient controlled environment and free access to feed and
      water. There were no significant differences in body weight gain, feed intake and
      feed conversion ratio (FCR) at terminal period among treatments (p>0.05).
      Relative weights of liver, spleen, abdominal fat and tissue muscle of breast
      obtained from each anti-SE bacteriophage treatment were similar to control, with
      a slightly higher value in anti-SE bacteriophage 0.2%. In addition, a numerical
      difference of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic
      transaminase (GPT) and LDL cholesterol level was observed in the 0.2% anti-SE
      bacteriophage application even though blood profiles were not significantly
      affected by supplemented levels of anti-SE bacteriophage (p>0.05). In the result
      of a 14 d record after Salmonella enteritidis challenge of 160 birds from 4
      previous treatments, mortality was linearly decreased with increasing anti-SE
      bacteriophage level (p<0.05), and Salmonella enteritidis concentration in the
      cecum was decreased with increasing levels of anti-SE bacteriophage (p<0.05).
      Based on the results of this study, it is considered that supplementation of 0.2%
      anti-SE bacteriophage may not cause any negative effect on growth, meat
      production, and it reduces mortality after Salmonella enteritidis challenge.
      These results imply to a possible use of anti-SE bacteriophage as an alternative
      feed additive instead of antibiotics in broilers diet. 

PMID- 25049802
TI  - Dietary alpha lipoic Acid improves body composition, meat quality and decreases
      collagen content in muscle of broiler chickens.
AB  - A total of 192 broiler chicks were used to evaluate the influence of dietary
      alpha-lipoic acid (ALA) on growth performance, carcass characteristics and meat
      quality of broiler chickens with the purpose of developing a strategy to prevent
      the occurrence of pale, soft, and exudative (PSE) meat and to improve the meat
      quality of broilers. At 22 d of age, birds were allocated to 4 ALA treatments (0,
      400, 800, and 1200 ppm). The results showed that dietary ALA significantly
      decreased average feed intake (AFI), average daily gain (ADG), final live body
      weight (BW) and carcass weight (p<0.05), while no difference in feed conversion
      ratio (FCR) was detected among chickens fed with and without ALA. Abdominal fat
      weight significantly decreased (p<0.05) for broilers fed 800 and 1200 ppm ALA.
      However when calculated as the percentage of carcass weight there was no
      significant difference between control and ALA treatments. Meat quality
      measurements showed that dietary ALA regulated postmortem glycolysis and improved
      meat quality as evidenced by increased muscle pH and decreased drip loss of meat
      (p<0.05). Although ALA did not change the tenderness of meat as indicated by meat
      shear force, dietary ALA decreased collagen content and mRNA expression of COL3A1
      gene (p<0.05). In conclusion, the results indicate that dietary ALA may
      contribute to the improvement of meat quality in broilers. 

PMID- 25049803
TI  - Determining of the Effect of Lysine:calorie Ratio on Growth Performance and Blood
      Urea Nitrogen of Growing Barrows and Gilts in Hot Season and Cool Season in a
      Commercial Environment.
AB  - Two experiments were conducted to determine an optimum Lys:calorie ratio (g of
      total dietary Lys/Mcal of DE) for growing barrows and gilts in cool and hot
      seasons in a commercial environment. In Exp. 1, 96 barrows and 96 gilts were
      randomly allocated in 1 of 4 dietary treatments (2.7, 3.0, 3.3, 3.6 g of Lys/Mcal
      of DE). Each treatment had 12 replicate pens with 4 pigs per pen. The experiment
      lasted for 34 d in the cool season (March 12th to April 15th). Diets were based
      on corn-wheat-soybean meal. Lys:calorie ratio were attained by adjusting the
      amount of corn and soybean and supplementation of crystalline Lys. Total Lys
      intake and available Lys intake were increased (p<.05) as dietary Lys:calorie
      ratio increased. The BUN concentration on d 34 for barrows, and BUN change for
      barrows and gilts linearly increased (p<0.05) in response to increasing dietary
      Lys:calorie ratio. For gilts, back fat was decreased and then increased
      (Quadratically, p<0.05) as increasing dietary lys:calorie ratio. Exp. 2 had a
      similar design as Exp. 1 with the exception that Exp. 2 was conducted in hot
      season (June 30th to September 11th) for 42 d. Diet of Exp. 2 was the same as
      Exp. 1. Total Lys intake and available Lys intake increased (p<0.05) as dietary
      Lys:calorie increased. On d 42, the BUN concentration increased (p<0.05) in
      response to the increasing dietary Lys:calorie ratio. In conclusion, dietary
      Lys:calorie ratio of 2.7 g of Lys/Mcal of DE could satisfy the requirement of 25
      to 50 kg growing pigs. Increasing dietary Lys:calorie ratio could increase BUN
      concentration in growing pigs. 

PMID- 25049804
TI  - Use of vitamin d3 and its metabolites in broiler chicken feed on performance,
      bone parameters and meat quality.
AB  - The objective of this experiment was to assess the use of different vitamin D
      metabolites in the feed of broiler chickens and the effects of the metabolites on
      performance, bone parameters and meat quality. A total of 952 one-day-old male
      broiler chicks were distributed in a completely randomised design, with four
      treatments, seven replicates and 34 birds per experimental unit. The treatments
      consisted of four different sources of vitamin D included in the diet, D3,
      25(OH)D3, 1,25(OH)2D3, and 1alpha(OH)D3, providing 2000 and 1600 IU of vitamin D
      in the starter (1 to 21 d) and growth phases (22 to 42 d), respectively. Mean
      weight, feed:gain and weight gain throughout the rearing period were less in
      animals fed 1alpha(OH)D3 when compared with the other treatments (p<0.05). No
      significant differences were noted among the treatments (p>0.05) for various bone
      parameters. Meat colour differed among the treatments (p>0.05). All of the
      metabolites used in the diets, with the exception of 1alpha(OH)D3, can be used
      for broiler chickens without problems for performance and bone quality, however,
      some aspects of meat quality were affected. 

PMID- 25049805
TI  - Effects of dietary olive oil on growth performance, carcass parameters, serum
      characteristics, and Fatty Acid composition of breast and drumstick meat in
      broilers.
AB  - This experiment was conducted to evaluate the effects of dietary olive oil on
      growth performance, carcass parameters, serum characteristics, and fatty acid
      composition of breast and drumstick meat in broiler chickens. A total of 480
      broilers were randomly allotted into three dietary treatments, including T (basal
      diet, 5% tallow), O1 (2% olive oil+3% tallow), and O2 (5% olive oil). During d 0
      to 21, broilers fed the diet supplemented with 5% olive oil showed lower (p<0.05)
      body weight gain (BWG) and feed intake (FI) compared with those fed the T diet.
      Serum triglyceride concentration was reduced (p<0.05), while high density
      lipoprotein (HDL)-cholesterol concentration was increased (p<0.05) in the O2
      treatment group compared with the T and O1 treatment groups. The addition of
      olive oil to the diets induced a reduction (p<0.05) in the total saturated fatty
      acid (SFA) contents in breast and drumstick meat, and increased (p<0.05) the
      total unsaturated fatty acid (USFA) contents and USFA/SFA ratios. In conclusion,
      a diet with 5% olive oil could decrease BWG and FI of broilers during the starter
      period (wk 0 to 3), and cause an increase in the serum HDL-cholesterol level,
      while decreasing the serum triglyceride concentration. Furthermore, USFA level
      and USFA/SFA ratios in breast and drumstick meat were increased by dietary
      supplementation of 2 or 5% olive oil. 

PMID- 25049806
TI  - Selection of Reliable Reference Genes for Real-time qRT-PCR Analysis of Zi Geese
      (Anser anser domestica) Gene Expression.
AB  - Zi geese (Anser anser domestica) belong to the white geese and are excellent
      layers with a superior feed-to-egg conversion ratio. Quantitative gene expression
      analysis, such as Real-time qRT-PCR, will provide a good understanding of ovarian
      function during egg-laying and consequently improve egg production. However, we
      still don't know what reference genes in geese, which show stable expression,
      should be used for such quantitative analysis. In order to reveal such reference
      genes, the stability of seven genes were tested in five tissues of Zi geese.
      METHODOLOGY/PRINCIPAL FINDINGS: The relative transcription levels of genes
      encoding hypoxanthine guanine phosphoribosyl transferase 1 (HPRT1), beta-actin
      (ACTB), beta-tubulin (TUB), glyceraldehyde-3-phosphate-dehydrogenase (GADPH),
      succinate dehydrogenase flavoprotein (SDH), 28S rRNA (28S) and 18S rRNA (18S)
      have been quantified in heart, liver, kidney, muscle and ovary in Zi geese
      respectively at different developmental stages (1 d, 2, 4, 6 and 8 months). The
      expression stability of these genes was analyzed using geNorm, NormFinder and
      BestKeeper software. CONCLUSIONS: The expression of 28S in heart, GAPDH in liver
      and ovary, ACTB in kidney and HPRT1 in muscle are the most stable genes as
      identified by the three different analysis methods. Thus, these genes are
      recommended for use as candidate reference genes to compare mRNA transcription in
      various developmental stages of geese.

PMID- 25049807
TI  - Dynamics of air temperature, velocity and ammonia emissions in enclosed and
      conventional pig housing systems.
AB  - This study aimed to compare the dynamics of air temperature and velocity under
      two different ventilation and housing systems during summer and winter in Korea.
      The NH3 concentration of both housing systems was also investigated in relation
      to the pig's growth. The ventilation systems used were; negative pressure type
      for the enclosed pig house (EPH) and natural airflow for the conventional pig
      house (CPH). Against a highly fluctuating outdoor temperature, the EPH was able
      to maintain a stable temperature at 24.8 to 29.1 degrees C during summer and 17.9
      to 23.1 degrees C during winter whilst the CPH had a wider temperature variance
      during summer at 24.7 to 32.3 degrees C. However, the temperature fluctuation of
      the CPH during winter was almost the same with that of EPH at 14.5 to 18.2
      degrees C. The NH3 levels in the CPH ranged from 9.31 to 16.9 mg/L during summer
      and 5.1 to 19.7 mg/L during winter whilst that of the EPH pig house was 7.9 to
      16.1 mg/L and 3.7 to 9.6 mg/L during summer and winter, respectively. These
      values were less than the critical ammonia level for pigs with the EPH
      maintaining a lower level than the CPH in both winter and summer. The air
      velocity at pig nose level in the EPH during summer was 0.23 m/s, enough to
      provide comfort because of the unique design of the inlet feature. However, no
      air movement was observed in almost all the lower portions of the CPH during
      winter because of the absence of an inlet feature. There was a significant
      improvement in weight gain and feed intake of pigs reared in the EPH compared to
      the CPH (p<0.05). These findings proved that despite the difference in the
      housing systems, a stable indoor temperature was necessary to minimize the impact
      of an avoidable and highly fluctuating outdoor temperature. The EPH consistently
      maintained an effective indoor airspeed irrespective of season; however the CPH
      had defective and stagnant air at pig nose level during winter. Characteristics
      of airflow direction and pattern were consistent relative to housing system
      during both summer and winter but not of airspeed. The ideal air velocity
      measurement favored the EPH and therefore can be appropriate for the Korean
      environment. Further emphasis on its cost effectiveness will be the subject of
      future investigations. 

PMID- 25049809
TI  - Polymorphism of NLRP3 Gene and Association with Susceptibility to Digestive
      Disorders in Rabbit.
AB  - NLR family pyrin domain containing 3 (NLRP3) is a key component of the
      inflammasome, whose assembly is a crucial part of the innate immune response. The
      aim of the present study was to evaluate the association between exon 3
      polymorphisms of NLRP3 and the susceptibility to digestive disorders in rabbits.
      In total, five coding single-nucleotide polymorphisms (cSNPs) were identified;
      all of which are synonymous. Among them, c.456 C> and c.594 G> were further
      genotyped for association analysis based on case-control design (n =162 vs n
      =102). Meanwhile, growing rabbits were experimentally induced to digestive
      disorders by feeding a fiber-deficient diet, subsequently they were subjected to
      mRNA expression analysis. Association analysis revealed that haplotype H1 (the
      two cSNPs: GT) played a potential protective role against digestive disorders
      (p<0.001). The expression of NLRP3 in the group H1HX1 (H1HX1 is composed of H1H1,
      H1H3 and H1H4) was the lowest among four groups which were classified by
      different types of diplotypes. Those results suggested that the NLRP3 gene was
      significantly associated with susceptibility to digestive disorders in rabbit. 

PMID- 25049808
TI  - A New Insight into the Role of Calpains in Post-mortem Meat Tenderization in
      Domestic Animals: A review.
AB  - Tenderness is the most important meat quality trait, which is determined by
      intracellular environment and extracellular matrix. Particularly, specific
      protein degradation and protein modification can disrupt the architecture and
      integrity of muscle cells so that improves the meat tenderness. Endogenous
      proteolytic systems are responsible for modifying proteinases as well as the meat
      tenderization. Abundant evidence has testified that calpains (CAPNs) including
      calpain I (CAPN1) and calpastatin (CAST) have the closest relationship with
      tenderness in livestock. They are involved in a wide range of physiological
      processes including muscle growth and differentiation, pathological conditions
      and post-mortem meat aging. Whereas, Calpain3 (CAPN3) has been established as an
      important activating enzyme specifically expressed in livestock's skeletal
      muscle, but its role in domestic animals meat tenderization remains
      controversial. In this review, we summarize the role of CAPN1, calpain II (CAPN2)
      and CAST in post-mortem meat tenderization, and analyse the relationship between
      CAPN3 and tenderness in domestic animals. Besides, the possible mechanism
      affecting post-mortem meat aging and improving meat tenderization, and current
      possible causes responsible for divergence (whether CAPN3 contributes to animal
      meat tenderization or not) are inferred. Only the possible mechanism of CAPN3 in
      meat tenderization has been confirmed, while its exact role still needs to be
      studied further. 

PMID- 25049810
TI  - Association of the porcine cluster of differentiation 4 gene with T lymphocyte
      subpopulations and its expression in immune tissues.
AB  - Cluster of differentiation 4 (CD4) is mainly expressed on CD4(+) T cells, which
      plays an important role in immune response. The aim of this study was to detect
      the association between polymorphisms of the CD4 gene and T lymphocyte
      subpopulations in pigs, and to investigate the effects of genetic variation on
      the CD4 gene expression level in immune tissues. Five missense mutations in the
      CD4 gene were identified using DNA pooling sequencing assays, and two main
      haplotypes (CCTCC and AGCTG) in strong linkage disequilibrium (with frequencies
      of 50.26% and 46.34%, respectively) were detected in the population of Large
      White pigs. Our results indicated that the five SNPs and the two haplotypes were
      significantly associated with the proportions of CD4(-)CD8(-), CD4(+)CD8(+),
      CD4(+)CD8(-), CD4(+) and CD4(+)/CD8(+) in peripheral blood (p<0.05). Gene
      expression analysis showed the mRNA level of the CD4 gene in thymus was
      significantly higher than that in lymph node and spleen (p<0.05). However, no
      significant difference was observed between animals with CCTCC/CCTCC genotype and
      animals with AGCTG/AGCTG genotype in the three immune tissues (p>0.05). These
      results indicate that the CD4 gene may influence T lymphocyte subpopulations and
      can be considered as a candidate gene affecting immunity in pigs. 

PMID- 25049811
TI  - Genetic parameter estimation in seedstock Swine population for growth
      performances.
AB  - The objective of this study was to estimate genetic parameters that are to be
      used for across-herd genetic evaluations of seed stock pigs at GGP level.
      Performance data with pedigree information collected from swine breeder farms in
      Korea were provided by Korea Animal Improvement Association (AIAK). Performance
      data were composed of final body weights at test days and ultrasound measures of
      back fat thickness (BF), rib eye area (EMA) and retail cut percentage (RCP).
      Breeds of swine tested were Landrace, Yorkshire and Duroc. Days to 90 kg body
      weight (DAYS90) were estimated with linear function of age and ADG calculated
      from body weights at test days. Ultrasound measures were taken with A-mode
      ultrasound scanners by trained technicians. Number of performance records after
      censoring outliers and keeping records pigs only born from year 2000 were of
      78,068 Duroc pigs, 101,821 Landrace pigs and 281,421 Yorkshire pigs. Models
      included contemporary groups defined by the same herd and the same seasons of
      births of the same year, which was regarded as fixed along with the effect of sex
      for all traits and body weight at test day as a linear covariate for ultrasound
      measures. REML estimation was processed with REMLF90 program. Heritability
      estimates were 0.40, 0.32, 0.21 0.39 for DAYS90, ADG, BF, EMA, RCP, respectively
      for Duroc population. Respective heritability estimates for Landrace population
      were 0.43, 0.41, 0.22, and 0.43 and for Yorkshire population were 0.36, 0.38,
      0.22, and 0.42. Genetic correlation coefficients of DAYS90 with BF, EMA, or RCP
      were estimated to be 0.00 to 0.09, -0.15 to -0.25, 0.22 to 0.28, respectively for
      three breeds populations. Genetic correlation coefficients estimated between BF
      and EMA was -0.33 to -0.39. Genetic correlation coefficient estimated between BF
      and RCP was high and negative (-0.78 to -0.85) but the environmental correlation
      coefficients between these two traits was medium and negative (near -0.35), which
      describes a highly correlated genetic response to selection on one or the other
      of these traits. Genetic Trends of all three breeds tend to be towards bigger EMA
      or greater RCP and shorter DAYS90 especially from generations born after year
      2000. 

PMID- 25049812
TI  - Comparative Analysis of Nkx2-5/GATA4/TBX5 Expression in Chicken, Quail and
      Chicken-quail Hybrids during the Early Stage of Cardiac Development in Embryos.
AB  - The present study makes an investigation into expression of genes related to
      cardiac development in chicken, quail and chicken-quail hybrids during the early
      stage of embryogenesis. Real-time PCR was used to detect mRNA expressions of Nkx2
      5, GATA4 and TBX5 in the heart of chicken, quail and chicken-quail hybrids
      embryos during the 3rd to 7th days of incubation. Results showed that NKX2-5 mRNA
      displayed a similar expression trend in chicken, quail and chicken-quail hybrids.
      The initial and highest expression of Nkx2-5 was focused on the 3rd day of
      incubation, then it declined till 5th day of incubation, thereafter, it
      fluctuated. Expression of Nkx2-5 gene in quail was significantly higher than in
      chicken and chicken-quail hybrids, and no significant difference was observed
      between the two latter species. GATA4 mRNA showed a similar expression trend
      between chicken and quail, which displayed a steady increase from 3rd to 6th d,
      then, the expression level decreased. However, GATA4 mRNA expression in chicken
      quail hybrids was significantly higher than that in chicken and quail from 3rd to
      5th d (p<0.01), but significantly lower than that in chicken and quail during the
      later stage of the experiment (p<0.05), due to the dramatic drop from 5th d
      onwards (p<0.01). TBX5 mRNA expression in chicken and quail showed the same trend
      as GATA4 expressed in the two species. Furthermore, TBX5 expression in chicken
      quail hybrids was significantly higher than that in chicken and quail during the
      whole course of experiment, although relatively lower TBX5 expression was
      detected in the early stage. In conclusion, Nkx2-5, GATA4 and TBX5 genes showed
      dynamic changes during the process of cardiac development in chicken, quail and
      their hybrids embryos. In addition, the expression trend in chicken was similar
      to that in quail, and there was no significant difference for gene expression
      level, except NKX2-5. However, expression of these genes in chicken-quail hybrids
      was significantly different from their parents, the difference mechanism needs to
      be further explored. 

PMID- 25049813
TI  - Polymorphisms in the Promoter Region of the Chinese Bovine PPARGC1A Gene.
AB  - The peroxisome proliferator-activated receptor gamma coactivator-1 alpha protein,
      encoded by the PPARGC1A gene, plays an important role in energy homeostasis. The
      genetic variations within the PPARGC1A gene promoter region were scanned in 808
      Chinese native bovines belonging to three cattle breeds and yaks. A total of 6
      SNPs and one 4 bp insertion variation in the promoter region of the bovine
      PPARGC1A gene were identified: SNP -259 T>A, -301_-298insCTTT, -915 A>G, -1175
      T>G, -1590 C>T, -1665 C>T and -1690 G>A, which are in the binding sites of some
      important transcription factors: sex-determining region Y (SRY), myeloid-specific
      zinc finger-1 (MZF-1) and octamer factor 1(Oct-1). It is expected that these
      polymorphisms may regulate PPARGC1A gene transcription and might have
      consequences at a regulatory level. 

PMID- 25049814
TI  - Ovarian Follicular Dynamics, Ovarian Follicular Growth, Oocyte Yield, In vitro
      Embryo Production and Repeated Oocyte Pick Up in Thai Native Heifers Undergoing
      Superstimulation.
AB  - The objective of this study was to compare the effectiveness of the protocols for
      superstimulation of follicular growth in Thai native heifers. Heifers (n = 20)
      were randomly divided into four groups of five heifers/group. Heifers were given
      a single dose by i.m. administration of 100 mg Follicle Stimulating Hormone
      dissolved in polyvinylpyrrolidone (FSHp) at 24 h. Ovum pick up (OPU) occurred at
      72 h (F24O72 protocol; Group 1) or 96 h (F24O96 protocol; Group 2), and at 36 h
      and OPU at 72 h (F36O72 protocol; Group 3) or 96 h (F36O96 protocol; Group 4)
      after follicular ablation. The dynamics of ovarian follicular growth were
      monitored by twice-daily ultrasonographic examinations. Blood sample collections
      were performed every 12 h after initiation of treatment for assessment of FSH, E2
      and P4 profiles. All heifers were subjected to eight repeated sequential sessions
      of OPU. The follicular deviation commenced 24+/-5.32 h after follicular ablation
      in all groups. The circulatory FSH surged quickly from 24 to 36 h (>0.8 ng/ml)
      after follicular ablation and circulatory estrogen levels steadily increased from
      36 h until OPU in all groups. At the end of the OPU sessions, the mean number of
      aspirated follicles/heifer/session in F36O72 protocol (Group 3) and F36O96
      protocol (Group 4) were higher than in the two other groups (p<0.05). The number
      of cumulus-oocyte complexes (COCs), cleaved and day 8 blastocysts rates in the
      F36O72 protocol (Group 3) were higher than in the other groups (p<0.05). It can
      be concluded that a single dose i.m. administration of 100 mg FSHp at 36 h and
      OPU at 72 h after follicular ablation (F36O72 protocol; Group 3) was the most
      effective protocol for superstimulation of follicular growth for repeated OPU and
      subsequent in vitro embryo production in Thai native heifers. 

PMID- 25049815
TI  - Effect of Dipeptides on In vitro Maturation, Fertilization and Subsequent
      Embryonic Development of Porcine Oocytes.
AB  - The effects of amino acids and dipeptides on in vitro production of porcine
      embryos and accumulation of ammonia in culture medium during developmental stages
      were examined in this study. The maturation, fertilization and development of
      embryonic cultures were performed in modified Tissue culture medium (mTCM)-199
      supplemented with 10% (v/v) porcine follicular fluid, modified Tyrode's albumin
      lactate pyruvate (mTALP) medium, and modified North Carolina State University
      (mNCSU)-23 medium, respectively. In addition, amino acids and dipeptides of
      different concentrations and combinations were used to treat the embryos. The
      addition of L-alanyl-L-glutamine (AlnGln)+L-glycyl-L-glutamine (GlyGln)
      significantly (p<0.05) improved oocyte maturation, fertilization and the
      incorporation and oxidation of (14)C(U)-glucose when compared to the control
      group and other treatment groups. Additionally, 2-4 cell, 8-16 cell, morula and
      blastocyst development increased significantly (p<0.05) following treatment with
      AlnGln+GlyGln when compared to the control group and other treatment groups,
      while this treatment reduced the accumulation of ammonia. Taken together, these
      findings suggest that treatment with AlnGln+GlyGln may play an important role in
      increasing the rate of porcine oocyte maturation, fertilization and embryonic
      development by reducing the level of accumulated ammonia measured in the culture
      media. 

PMID- 25049816
TI  - Effects of Feeding Corn-lablab Bean Mixture Silages on Nutrient Apparent
      Digestibility and Performance of Dairy Cows.
AB  - This study estimated the fermentation characteristics and nutrient value of corn
      lablab bean mixture silages relative to corn silages. The effects of feeding corn
      lablab bean mixture silages on nutrient apparent digestibility and milk
      production of dairy cows in northern China were also investigated. Three
      ruminally cannulated Holstein cows were used to determine the ruminal digestion
      kinetics and ruminal nutrient degradability of corn silage and corn-lablab bean
      mixture silages. Sixty lactating Holstein cows were randomly divided into two
      groups of 30 cows each. Two diets were formulated with a 59:41 forage:
      concentrate ratio. Corn silage and corn-lablab bean mixture silages constituted
      39.3% of the forage in each diet, with Chinese wildrye hay constituting the
      remaining 60.7%. Corn-lablab bean mixture silages had higher lactic acid, acetic
      acid, dry matter (DM), crude protein (CP), ash, Ca, ether extract concentrations
      and ruminal nutrient degradability than monoculture corn silage (p<0.05). Neutral
      detergent fiber (NDF) and acid detergent fiber (ADF) concentrations of corn
      lablab bean mixture silages were lower than those of corn silage (p<0.05). The
      digestibility of DM, CP, NDF, and ADF for cows fed corn-lablab bean mixture
      silages was higher than for those fed corn silage (p<0.05). Feeding corn-lablab
      bean mixture silages increased milk yield and milk protein of dairy cows when
      compared with feeding corn silage (p<0.05). The economic benefit for cow fed corn
      lablab bean mixture silages was 8.43 yuan/day/cow higher than that for that fed
      corn silage. In conclusion, corn-lablab bean mixture improved the fermentation
      characteristics and nutrient value of silage compared with monoculture corn. In
      this study, feeding corn-lablab bean mixture silages increased milk yield, milk
      protein and nutrient apparent digestibility of dairy cows compared with corn
      silage in northern China. 

PMID- 25049817
TI  - The Effect of Plant Extracts on In-vitro Ruminal Fermentation, Methanogenesis and
      Methane-related Microbes in the Rumen.
AB  - The effect on methanogens attached to the surface of rumen ciliate protozoa by
      the addition of plant extracts (pine needles and ginkgo leaves) was studied with
      particular reference to their effectiveness for decreasing methane emission. The
      plant extracts (pine needles and ginkgo leaves) were added to an in vitro
      fermentation incubated with rumen fluid. The microbial population including
      bacteria, ciliated-associated methanogen, four different groups of methanogens
      and Fibrobacter succinogenes were quantified by using the real-time PCR. Gas
      profiles including methane, carbon dioxide and hydrogen, and runinal fermentation
      characteristics were observed in vitro. The methane emission from samples with an
      addition of individual juices from pine needles, ginkgo leaves and 70% ethanol
      extract from ginko leaves was significantly lower (p<0.05, 27.1, 28.1 and 28.1 vs
      34.0 ml/g DM) than that of the control, respectively. Total VFAs in samples with
      an addition of any of the plant extracts were significantly lower than that of
      the control (p<0.05) as well. The order Methanococcales and the order
      Methanosarcinales were not detected by using PCR in any incubated mixtures. The
      ciliate-associated methanogens population decreased from 25% to 49% in the plant
      extacts as compared to control. We speculate that the supplementation of juice
      from pine needles and ginkgo leaves extract (70% ethanol extract) decreased the
      protozoa population resulting in a reduction of methane emission in the rumen and
      thus inhibiting methanogenesis. The order Methanobacteriales community was
      affected by addition of all plant extracts and decreased to less than the
      control, while the order Methanomicrobiales population showed an increase to more
      than that of the control. The F. succinogenes, the major fibrolytic
      microorganism, population in all added plant extracts was increased to greater
      than that of the control. In conclusion, pine needles and ginkgo leaves extracts
      appear to have properties that decrease methanogenesis by inhibiting protozoa
      species and may have a potential for use as additives for ruminants. 

PMID- 25049818
TI  - Effects of Branched-chain Amino Acids on In vitro Ruminal Fermentation of Wheat
      Straw.
AB  - This study investigates the effects of three branched-chain amino acids (BCAA;
      valine, leucine, and isoleucine) on the in vitro ruminal fermentation of wheat
      straw using batch cultures of mixed ruminal microorganisms. BCAA were added to
      the buffered ruminal fluid at a concentration of 0, 2, 4, 7, or 10 mmol/L. After
      72 h of anaerobic incubation, pH, volatile fatty acids (VFA), and ammonia
      nitrogen (NH3-N) in the ruminal fluid were determined. Dry matter (DM) and
      neutral detergent fiber (NDF) degradability were calculated after determining the
      DM and NDF in the original material and in the residue after incubation. The
      addition of valine, leucine, or isoleucine increased the total VFA yields
      (p<=0.001). However, the total VFA yields did not increase with the increase of
      BCAA supplement level. Total branched-chain VFA yields linearly increased as the
      supplemental amount of BCAA increased (p<0.001). The molar proportions of acetate
      and propionate decreased, whereas that of butyrate increased with the addition of
      valine and isoleucine (p<0.05). Moreover, the proportions of propionate and
      butyrate decreased (p<0.01) with the addition of leucine. Meanwhile, the molar
      proportions of isobutyrate were increased and linearly decreased (p<0.001) by
      valine and leucine, respectively. The addition of leucine or isoleucine resulted
      in a linear (p<0.001) increase in the molar proportions of isovalerate. The
      degradability of NDF achieved the maximum when valine or isoleucine was added at
      2 mmol/L. The results suggest that low concentrations of BCAA (2 mmol/L) allow
      more efficient regulation of ruminal fermentation in vitro, as indicated by
      higher VFA yield and NDF degradability. Therefore, the optimum initial dose of
      BCAA for in vitro ruminal fermentation is 2 mmol/L. 

PMID- 25049819
TI  - Effect of carbohydrate sources and levels of cotton seed meal in concentrate on
      feed intake, nutrient digestibility, rumen fermentation and microbial protein
      synthesis in young dairy bulls.
AB  - The objective of this study was to investigate the effect of levels of cottonseed
      meal with various carbohydrate sources in concentrate on feed intake, nutrient
      digestibility, rumen fermentation and microbial protein synthesis in dairy bulls.
      Four, 6 months old dairy bulls were randomly assigned to receive four dietary
      treatments according to a 2*2 factorial arrangement in a 4*4 Latin square design.
      Factor A was carbohydrate source; cassava chip (CC) and cassava chip+rice bran in
      the ratio of 3:1 (CR3:1), and factor B was cotton seed meal levels in the
      concentrate; 109 g CP/kg (LCM) and 328 g CP/kg (HCM) at similar overall CP levels
      (490 g CP/kg). Bulls received urea-lime treated rice straw ad libitum and were
      supplemented with 10 g of concentrate/kg BW. It was found that carbohydrate
      source and level of cotton seed meal did not have significant effects on ruminal
      pH, ammonia nitrogen concentration, microbial protein synthesis or feed intake.
      Animals which received CC showed significantly higher BUN concentration, ruminal
      propionic acid and butyric acid proportions, while dry matter, organic matter
      digestibility, populations of total viable bacteria and proteolytic bacteria were
      lower than those in the CR3:1 treatment. The concentration of total volatile
      fatty acids was higher in HCM than LCM treatments, while the concentration of
      butyric acid was higher in LCM than HCM treatments. The population of proteolytic
      bacteria with the LCM treatments was higher than the HCM treatments; however
      other bacteria groups were similar among the different levels of cotton seed
      meal. Bulls which received LCM had higher protein digestibility than those
      receiving HCM. Therefore, using high levels of cassava chip and cotton seed meal
      might positively impact on energy and nitrogen balance for the microbial
      population in the rumen of the young dairy bull. 

PMID- 25049820
TI  - Effects of enzyme treated palm kernel expeller on metabolizable energy, growth
      performance, villus height and digesta viscosity in broiler chickens.
AB  - This study examined whether pre-treating palm kernel expeller (PKE) with
      exogenous enzyme would degrade its fiber content; thus improving its
      metabolizable energy (ME), growth performance, villus height and digesta
      viscosity in broiler chickens fed diets containing PKE. Our results showed that
      enzyme treatment decreased (p<0.05) hemicellulose and cellulose contents of PKE
      by 26.26 and 32.62%, respectively; and improved true ME (TME) and its nitrogen
      corrected value (TMEn) by 38% and 33%, respectively, compared to the raw sample.
      Average daily gain (ADG), feed intake and feed conversion ratio (FCR) of chickens
      fed on different dietary treatments in the grower period were not significantly
      different. Although there was no difference in feed intake (p>0.05) among
      treatment groups in the finisher period, ADG of chickens in the control (PKE-free
      diet) was higher (p<0.05) than in all treatment groups fed either 20 or 30% PKE,
      irrespective of with or without enzyme treatment. However, ADG of birds fed with
      20% PKE was higher than those fed with 30% PKE. The FCR of chickens in the
      control was the lowest (2.20) but not significantly different from those fed 20%
      PKE diets while birds in the 30% PKE diets recorded higher (p>0.05) FCR. The
      intestinal villus height and crypt depth (duodenum, jejunum and ileum) were not
      different (p>0.05) among treatments except for duodenal crypt depth. The villus
      height and crypt depth of birds in enzyme treated PKE diets were higher (p<0.05)
      than those in the raw PKE groups. Viscosity of the intestinal digesta was not
      different (p>0.05) among treatments. Results of this study suggest that exogenous
      enzyme is effective in hydrolyzing the fiber (hemicellulose and cellulose)
      component and improved the ME values of PKE, however, the above positive effects
      were not reflected in the growth performance in broiler chickens fed the enzyme
      treated PKE compared to those received raw PKE. The results suggest that PKE can
      be included up to 5% in the grower diet and 20% in the finisher diet without any
      significant negative effect on FCR in broiler chickens. 

PMID- 25049821
TI  - Development of Gut Microbiota in a Mouse Model of Ovalbumin-induced Allergic
      Diarrhea under Sub-barrier System.
AB  - This study aimed to present a mouse model of ovalbumin (OVA) induced allergic
      diarrhea under a sub-barrier system and investigate the development of gut
      microbiota in this model. Male BALB/c mice were systemically sensitized with OVA
      or sham-sensitized with saline, and followed by oral OVA intubation, leading to
      OVA-specific acute diarrhea. Compared with sham-sensitized mice, sera OVA
      specific IgG1 and total IgE in OVA-sensitized mice were dramatically elevated,
      and the number of mast cells was greatly increased in the jejunum of the OVA
      sensitized mice. Principle component analysis of the DGGE profile showed that
      samples from group of OVA-sensitized mice and group of sham-sensitized mice were
      scattered into two different regions. Real-time PCR analysis showed that the
      number of 16S rRNA gene copies of Lactobacillus in the colon of OVA-sensitized
      mice decreased significantly, while there was no significant difference in the
      number of Bifidobacterium and total bacteria. In conclusion, OVA-specific
      allergic diarrhea was successfully induced under a sub-barrier system, and
      changes of allergic reactions during induction was coupled with changes in gut
      microbiota, especially the number of colonic Lactobacillus, but the role of gut
      microbiota in the development of food allergic reactions needs to be further
      evaluated. 

PMID- 25049822
TI  - Immobilization of the Antarctic Bacillus sp. LX-1 alpha-Galactosidase on Eudragit
      L-100 for the Production of a Functional Feed Additive.
AB  - Partially purified alpha-galactosidase from Bacillus sp. LX-1 was non-covalently
      immobilized on a reversibly soluble-insoluble polymer, Eudragit L-100, and an
      immobilization efficiency of 0.93 was obtained. The optimum pH of the free and
      immobilized enzyme was 6.5 to 7.0 and 7.0, respectively, while there was no
      change in optimum temperature between the free and immobilized alpha
      galactosidase. The immobilized alpha-galactosidase was reutilized six times
      without significant loss in activity. The immobilized enzyme showed good storage
      stability at 37 degrees C, retaining about 50% of its initial activity even after
      18 d at this temperature, while the free enzyme was completely inactivated. The
      immobilization of alpha-galactosidase from Bacillus sp. LX-1 on Eudragit L-100
      may be a promising strategy for removal of alpha-galacto-oligosaccharides such as
      raffinose and stachyose from soybean meal and other legume in feed industry. 

PMID- 25049823
TI  - Earlier Metabolizable Energy Intake Level Influences Heat Production during a
      Following 3-Day Fast in Laying Hens.
AB  - The present study was conducted to estimate energy requirements for maintenance
      in laying hens by using indirect calorimetry and energy balance. A total of 576
      28-wk-old Nongda-3 laying hens with dwarf gene were randomly allocated into four
      ME intake levels (86.57, 124.45, 166.63 and 197.20 kcal/kg body weight (BW)(0.75)
      per d) with four replicates each. After a 4 d adaptation period, 36 hens from one
      replicate were maintained in one of the two respiration chambers to measure the
      heat production (HP) for 3 d during the feeding period and subsequent 3 d fast.
      Metabolizable energy (ME) intake was partitioned between heat increment (HI), HP
      associated with activity, fasting HP (FHP) and retained energy (RE). The
      equilibrium FHP may provide an estimate of NE requirements for maintenance (NEm).
      Results showed that HP, HI and RE in the fed state increased with ME intake level
      (p<0.05). Based on the regression of HP on ME intake, the estimated ME
      requirements for maintenance (MEm) was 113.09 kcal/kg BW(0.75) per d when ME
      intake equals HP. The FHP was decreased day by day with the lowest value on the
      third day of starvation. Except for lowest ME intake level, the FHP increased
      with ME intake level on the first day of starvation (p<0.05). The FHP at the two
      higher ME intake levels were greater than that at the two lower ME intake levels
      (p<0.05) but no difference was found between the two lower ME intake levels.
      Linear regression of HP from the fed state to zero ME intake yielded a value of
      71.02 kcal/kg BW(0.75) per d, which is higher than the extrapolated FHP at zero
      ME intake (60.78, 65.23 and 62.14 kcal/kg BW(0.75) per d for the first, second
      and third day of fasting, respectively). Fasting time, lighting schedules,
      calculation methods and duration of adaptation of hens to changes in ME intake
      level should be properly established when using indirect calorimetry technique to
      estimate dietary NE content, MEm and NEm for laying hens. 

PMID- 25049824
TI  - The effect of level of crude protein and available lysine on finishing pig
      performance, nitrogen balance and nutrient digestibility.
AB  - Two trials were conducted to investigate the effect of decreasing the crude
      protein (CP) content of diets for finishing pigs containing two levels of
      available lysine on nutrient digestibility, nitrogen (N) balance and production
      performance. Ten finishing diets containing five levels of CP (on average 144,
      155, 168, 182 and 193 g/kg fresh basis) and two levels of available lysine (6.9
      and 8.2 g/kg fresh basis) were formulated. The diets were offered to pigs on a
      performance trial (n = 800 Large White (LW)*Landrace (LR) pigs) from 10 wk of age
      until finish at 21 wks+5 d of age. Average daily gain (ADG), average daily feed
      intake (ADFI) and feed conversion ratio (FCR) were calculated. In addition, a
      digestibility/N balance trial was conducted using pigs (n = 80 LW*LR) housed in
      metabolism crates. Digestibility of dry matter (DM), CP, oil, fibre and energy
      was determined. N balance values were determined through analysis of N content of
      urine and faeces ('as determined'). N balance values were also calculated using
      ADG values and assuming that 16% of growth is protein deposition ("as
      calculated"). Pig performance was poor between 10 and 13 wk of age which
      indicated that the dietary treatments were nutritionally inadequate for pigs less
      than 40 kg. There was a significant (p<0.01) quadratic effect of increasing CP
      level on feed intake, ADG and FCR from 10 to 13 wk which indicated that the lower
      CP levels did not supply adequate levels of essential or non-essential amino
      acids. There was no effect of increasing available lysine level throughout the
      early period, which in conjunction with the response in older pigs, suggested
      that both 8.2 and 6.9 g/kg available lysine were insufficient to drive optimum
      growth. There was a positive response (p<0.05) to increasing available lysine
      level from 13 wk to finish which indicated that 6.9 g/kg available lysine was not
      adequate for finishing pigs. Energy digestibility decreased with decreasing CP
      level of diets containing 6.9 g/kg available lysine which may be attributed to
      the higher fibre content of the lower CP diets. Nitrogen excretion (g/d) was
      lowered when dietary CP was reduced regardless of whether the values were
      determined through balance or calculated using ADG. Calculated N excretion
      decreased linearly (p<0.001) and quadratically (p<0.001) with decreasing dietary
      CP content. When the N balance figures calculated in this study were compared
      with those quoted in the Northern Ireland and English Nitrates Directive Action
      Programmes, N excretion was less per pig (wean to finish) offered a 169 g/kg CP,
      8.2 g/kg available lysine diet (2.39 kg vs 3.41 kg (Northern Ireland) and 2.93 kg
      (England)). 

PMID- 25049825
TI  - Evaluation of bacteriophage supplementation on growth performance, blood
      characteristics, relative organ weight, breast muscle characteristics and excreta
      microbial shedding in broilers.
AB  - A total of 720 1-d-old male broilers (Arbor Acres) with the initial BW = 45+/-2 g
      were used in a 32-d experiment. Birds were randomly allotted into 1 of 4
      treatments according to a completely random block design. Dietary treatments
      included: i) CON (basal diet), ii) ANT (CON+0.5 g antibiotics/kg feed (bacitracin
      methylene disalicylate)), iii) BP1 (CON+0.25 bacteriophage/kg feed), and iv) BP2
      (CON+0.5 g bacteriophage/kg feed). The BWG and FI were not affected by dietary
      treatments throughout the whole experiment, whereas BP2 treatment reduced
      (p<0.05) the feed conversion ratio compared with the CON treatment during 0 to 14
      d. The birds fed bacteriophages at the level of 0.25 g/kg increased (p<0.05) the
      relative liver weight. The inclusion of antibiotic and bacteriophage
      significantly reduced (p<0.05) the Escherichia coli and Salmonella concentration
      in the excreta compared with the NC group. Broilers fed the BP2 treatment had
      higher (p<0.05) lactobacillus counts compared with those fed NC and PC
      treatments. In conclusion, dietary supplementation of 0.5 g/kg bacteriophages
      increased feed efficiency and liver weight without effects on the breast muscle
      properties; also pathogens were inhibited by addition of bacteriophages. 

PMID- 25049826
TI  - Effects of Supplementation of beta-Mannanase in Corn-soybean Meal Diets on
      Performance and Nutrient Digestibility in Growing Pigs.
AB  - A total of 288 crossbred (Duroc*Landrace*Yorkshire) growing pigs were used in two
      experiments to investigate the effects of adding beta-mannanase to corn-soybean
      meal-based diets on pig performance and apparent total tract digestibility
      (ATTD). Both experiments lasted 28 d and were split into two phases namely 1 to
      14 days (phase 1) and 15 to 28 days (phase 2). In Exp. 1,144 pigs weighing
      23.60+/-1.59 kg BW were assigned to one of four corn-soybean meal-based diets
      containing 0, 200, 400 or 600 U/kg beta-mannanase. Increasing the level of beta
      mannanase increased weight gain (quadratic effect; p<0.01) and feed efficiency
      (linear and quadratic effect; p<0.01) during the second phase and the overall
      experiment. However, performance was unaffected (p>0.05) by treatment during
      phase 1. Increasing the amount of beta-mannanase in the diet improved (linear and
      quadratic effect; p<0.05) the ATTD of CP, NDF, ADF, calcium, and phosphorus
      during both phases. Based on the results of Exp. 1, the optimal supplementation
      level was determined to be 400 U/kg and this was the level that was applied in
      Exp. 2. In Exp. 2, 144 pigs weighing 23.50+/-1.86 kg BW were fed diets containing
      0 or 400 U/kg of beta-mannanase and 3,250 or 3,400 kcal/kg digestible energy (DE)
      in a 2*2 factorial design. beta-Mannanase supplementation increased (p<0.01)
      weight gain and feed efficiency while the higher energy content increased
      (p<0.01) feed intake and feed efficiency during both phases and overall.
      Increased energy content and beta-mannanase supplementation both increased
      (p<0.05) the ATTD of DM, CP, NDF, ADF, phosphorus, and GE during both phases.
      There were no significant interactions between energy level and beta-mannanase
      for any performance or digestibility parameter. In conclusion, the beta-mannanase
      used in the present experiment improved the performance of growing pigs fed diets
      based on corn and soybean. The mechanism through which the improvements were
      obtained appears to be related to improvements in ATTD. 

PMID- 25049827
TI  - Effects of serial passage on the characteristics and chondrogenic differentiation
      of canine umbilical cord matrix derived mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are often known to have a therapeutic potential in
      the cell-mediated repair for fatal or incurable diseases. In this study, canine
      umbilical cord MSCs (cUC-MSCs) were isolated from umbilical cord matrix (n = 3)
      and subjected to proliferative culture for 5 consecutive passages. The cells at
      each passage were characterized for multipotent MSC properties such as
      proliferation kinetics, expression patterns of MSC surface markers and self
      renewal associated markers, and chondrogenic differentiation. In results, the
      proliferation of the cells as determined by the cumulative population doubling
      level was observed at its peak on passage 3 and stopped after passage 5, whereas
      cell doubling time dramatically increased after passage 4. Expression of MSC
      surface markers (CD44, CD54, CD61, CD80, CD90 and Flk-1), molecule (HMGA2) and
      pluripotent markers (sox2, nanog) associated with self-renewal was negatively
      correlated with the number of passages. However, MSC surface marker (CD105) and
      pluripotent marker (Oct3/4) decreased with increasing the number of subpassage.
      cUC-MSCs at passage 1 to 5 underwent chondrogenesis under specific culture
      conditions, but percentage of chondrogenic differentiation decreased with
      increasing the number of subpassage. Collectively, the present study suggested
      that sequential subpassage could affect multipotent properties of cUC-MSCs and
      needs to be addressed before clinical applications. 

PMID- 25049828
TI  - Synergistic Effects of Electron-beam Irradiation and Leek Extract on the Quality
      of Pork Jerky during Ambient Storage.
AB  - To investigate the synergistic effect(s) of electron-beam (EB) irradiation and
      leek (Allium tuberosum Rottler) extract on the quality of pork jerky during
      ambient storage, we irradiated prepared pork jerky samples (control and samples
      with 0.5% and 1.0% leek extract) with EB technology at doses of 0, 1, 2, and 4
      kGy, stored them for 2 months at 25 degrees C, and analyzed them. Water activity
      was 0.73 to 0.77 in non-irradiated samples, and no significant difference in the
      water activity was observed between the samples treated with leek and the
      control. The total aerobic bacterial count was significantly decreased with an
      increase in the irradiation dose and leek extract addition when compared to that
      of the control (4.54+/-0.05 log CFU/g). Further, the Hunter color values (L*, a*,
      and b*) were found to be significantly decreased following leek extract addition
      and EB irradiation. However, the color values, especially the a* value of the
      irradiated samples significantly increased during storage. Notably, increasing
      the EB irradiation dose enhanced the peroxide value. Sensory evaluation revealed
      that irradiation decreased flavor and overall acceptability. Our findings suggest
      the use of EB irradiation in combination with leek extract to improve the
      microbiological safety of pork jerky. However, in order to meet market
      requirements, novel methods to enhance the sensory quality of pork jerky are
      warranted. 

PMID- 25049829
TI  - Identification of recently selected mutations driven by artificial selection in
      hanwoo (korean cattle).
AB  - Hanwoo have been subjected over the last seventy years to intensive artificial
      selection with the aim of improving meat production traits such as marbling and
      carcass weight. In this study, we performed a signature of selection analysis to
      identify recent positive selected regions driven by a long-term artificial
      selection process called a breeding program using whole genome SNP data. In order
      to investigate homozygous regions across the genome, we estimated iES (integrated
      Extended Haplotype Homozygosity SNP) for the each SNPs. As a result, we
      identified two highly homozygous regions that seem to be strong and/or recent
      positive selection. Five genes (DPH5, OLFM3, S1PR1, LRRN1 and CRBN) were included
      in this region. To go further in the interpretation of the observed signatures of
      selection, we subsequently concentrated on the annotation of differentiated genes
      defined according to the iES value of SNPs localized close or within them. We
      also described the detection of the adaptive evolution at the molecular level for
      the genes of interest. As a result, this analysis also led to the identification
      of OLFM3 as having a strong signal of selection in bovine lineage. The results of
      this study indicate that artificial selection which might have targeted most of
      these genes was mainly oriented towards improvement of meat production. 

PMID- 25049831
TI  - Investigation of MC1R SNPs and Their Relationships with Plumage Colors in Korean
      Native Chicken.
AB  - The melanocortin 1 receptor (MC1R) gene is related to the plumage color
      variations in chicken. Initially, the MC1R gene from 30 individuals was sequenced
      and nine polymorphisms were obtained. Of these, three and six single nucleotide
      polymorphisms (SNPs) were confirmed as synonymous and nonsynonymous mutations,
      respectively. Among these, three selected SNPs were genotyped using the
      restriction fragment length polymorphism (RFLP) method in 150 individuals from
      five chicken breeds, which identified the plumage color responding alleles. The
      neighbor-joining phylogenetic tree using MC1R gene sequences indicated three well
      differentiated different plumage pigmentations (eumelanin, pheomelanin and
      albino). Also, the genotype analyses indicated that the TT, AA and GG genotypes
      corresponded to the eumelanin, pheomelanin and albino plumage pigmentations at
      nucleotide positions 69, 376 and 427, respectively. In contrast, high allele
      frequencies with T, A and G alleles corresponded to black, red/yellow and white
      plumage color in 69, 376 and 427 nucleotide positions, respectively. Also, amino
      acids changes at position Asn23Asn, Val126Ile and Thr143Ala were observed in
      melanin synthesis with identified possible alleles, respectively. In addition,
      high haplotype frequencies in TGA, CGG and CAA haplotypes were well discriminated
      based on the plumage pigmentation in chicken breeds. The results obtained in this
      study can be used for designing proper breeding and conservation strategies for
      the Korean native chicken breeds, as well as for the developing breed
      identification markers in chicken. 

PMID- 25049830
TI  - Microarray analysis of genes involved with shell strength in layer shell gland at
      the early stage of active calcification.
AB  - The objective of this study was to get a comprehensive understanding of how genes
      in chicken shell gland modulate eggshell strength at the early stage of active
      calcification. Four 32-week old of purebred Xianju hens with consistent high or
      low shell breakage strength were grouped into two pairs. Using Affymetrix Chicken
      Array, a whole-transcriptome analysis was performed on hen's shell gland at 9 h
      post oviposition. Gene ontology enrichment analysis for differentially expressed
      (DE) transcripts was performed using the web-based GOEAST, and the validation of
      DE-transcripts was tested by qRT-PCR. 1,195 DE-transcripts, corresponding to 941
      unique genes were identified in hens with strong eggshell compared to weak shell
      hens. According to gene ontology annotations, there are 77 DE-transcripts
      encoding ion transporters and secreted extracellular matrix proteins, and at
      least 26 DE-transcripts related to carbohydrate metabolism or post-translation
      glycosylation modification; furthermore, there are 88 signaling DE-transcripts.
      GO term enrichment analysis suggests that some DE-transcripts mediate
      reproductive hormones or neurotransmitters to affect eggshell quality through a
      complex suite of biophysical processes. These results reveal some candidate genes
      involved with eggshell strength at the early stage of active calcification which
      may facilitate our understanding of regulating mechanisms of eggshell quality. 

PMID- 25049832
TI  - Improving Productive and Reproductive Performance of Holstein Dairy Cows through
      Dry Period Management.
AB  - To determine the effects of dry period (DP) length on milk yield, milk
      composition, some blood metabolites, complete blood count (CBC), body weight and
      score and follicular status, twenty five primiparous and multiparous Holstein
      cows were assigned to a completely randomized design with DP-60 (n = 13) and DP
      20 (n = 12) dry period lengths. Cows in the DP-60 produced more milk, protein,
      SNF, serum non-esterified fatty acids (NEFA) and beta hydroxyl butyrate acid
      (BHBA) compared with cows in DP-20 (p<=0.05). Serum glucose, blood urea nitrogen
      (BUN), urea, and glutamic oxaloacetic transaminase (GOT) were all similar among
      the treatments. Body Condition Score (BCS), body weight (BW), complete blood
      count (CBC) and health problems were similar between the treatments. Diameter of
      the first dominant follicle and diameter of the dominant follicle on d 14 were
      different among the treatments. Thus, results of this study showed that reducing
      the dry period length to DP-20 had a negative effect on milk production, milk
      composition and reproductive performance in Holstein dairy cows. 

PMID- 25049833
TI  - Presence of Transcription Factor OCT4 Limits Interferon-tau Expression during the
      Pre-attachment Period in Sheep.
AB  - Interferon-tau (IFNT) is thought to be the conceptus protein that signals
      maternal recognition of pregnancy in ruminants. We and others have observed that
      OCT4 expression persists in the trophectoderm of ruminants; thus, both CDX2 and
      OCT4 coexist during the early stages of conceptus development. The aim of this
      study was to examine the effect of CDX2 and OCT4 on IFNT gene transcription when
      evaluated with other transcription factors. Human choriocarcinoma JEG-3 cells
      were cotransfected with an ovine IFNT (-654-bp)-luciferase reporter (-654-IFNT
      Luc) construct and several transcription factor expression plasmids.
      Cotransfection of the reporter construct with Cdx2, Ets2 and Jun increased
      transcription of -654-IFNT-Luc by about 12-fold compared with transfection of the
      construct alone. When cells were initially transfected with Oct4 (0 h) followed
      by transfection with Cdx2, Ets2 and/or Jun 24 h later, the expression of -654
      IFNT-Luc was reduced to control levels. OCT4 also inhibited the stimulatory
      activity of CDX2 alone, but not when CDX2 was combined with JUN and/or ETS2.
      Thus, when combined with the other transcription factors, OCT4 exhibited little
      inhibitory activity towards CDX2. An inhibitor of the transcriptional coactivator
      CREB binding protein (CREBBP), 12S E1A, reduced CDX2/ETS2/JUN stimulated -654
      IFNT-Luc expression by about 40%, indicating that the formation of an appropriate
      transcription factor complex is required for maximum expression. In conclusion,
      the presence of OCT4 may initially minimize IFNT expression; however, as
      elongation proceeds, the increasing expression of CDX2 and formation of the
      transcription complex leads to greatly increased IFNT expression, resulting in
      pregnancy establishment in ruminants. 

PMID- 25049834
TI  - Effect of water hyacinth (eichhornia crassipes) silage on intake and nutrient
      digestibility in cattle fed rice straw and cottonseed cake.
AB  - Four crossbred Sindhi heifers with an average body weight (BW) of 135 kg and a
      mean age of 17 months were used to investigate the effect of feeding different
      combinations of rice straw and ensiled water hyacinth (EWH) supplemented with a
      source of protein in the form of cottonseed cake (CSC) on intake and
      digestibility. Four treatments consisting of graded levels of EWH were arranged
      in a 4*4 Latin square. The levels of EWH were set at: 0 (EWH0), 15 (EWH15), 30
      (EWH30), and 45% (EWH45) of an expected total dietary dry matter (DM) intake of
      30 g total DM per kg BW per day. Rice straw was offered ad libitum, while CSC was
      given at a fixed level of 5 g DM/kg body weight (BW). Voluntary intake and
      digestibility were measured consecutively in the 4 experimental periods which
      each lasted 28 days. The crude protein (CP) content of EWH, rice straw and CSC
      were 174, 53 and 370 g/kg DM, respectively. Rice straw had the highest neutral
      detergent fibre (NDFom) content (666 g/kg DM), followed by EWH (503 g/kg DM) and
      the lowest content was 418 g/kg DM in the CSC. The actual EWH contents in the
      consumed diets were 0, 17, 32 and 52% for EWH0, EWH15, EWH30 and EWH45,
      respectively. Rice straw intake decreased with level of EWH offered from 3049 for
      EWH0 to 1014 g/day for EWH45. Crude protein intake was 16, 25 and 33% higher
      (p<0.001) in EWH15, EWH30 and EWH45 treatments, respectively, as compared to
      EWH0. Digestibility of organic matter (OM), CP, NDFom and acid detergent fibre
      (ADFom) increased with increasing level of EWH offered. The highest OM
      digestibility (72.2%) was found for treatment EWH45 and the lowest (47.4%) for
      treatment EWH0. In spite of similar dietary CP contents, CP digestibility
      increased by 21 (EWH15), 31 (EWH30) and 40% (EWH45) with increasing level of EWH
      in comparison with treatment EWH0. It is concluded that increasing level of EWH
      in cattle diets considerably improved CP intake and digestibility of nutrients. 

PMID- 25049835
TI  - Effect of Oral Administration of Intact Casein on Gastrointestinal Hormone
      Secretion and Pancreatic alpha-Amylase Activity in Korean Native Steer.
AB  - Three Korean native steers (779+/-24 kg) fitted with duodenal cannulas were used
      in a 3*3 Latin square design to investigate the influence of oral administration
      of soluble proteins, intact casein (IC) and acid hydrolyzed casein (AHC), on
      gastrointestinal hormone (GIH) secretion in the blood and pancreatic alpha
      amylase activity in the duodenum. Oral treatment consisted of a basic diet
      (control), IC (C+100% protein), or AHC (C+80% amino acid, 20% peptide) for 21 d.
      Blood and duodenum samples were collected for measurement of serum GI hormones,
      and pancreatic alpha-amylase activity was determined at 900, 1030, 1330, 1630,
      and 1930 h after feeding on d 21 of treatment. The levels of serum
      cholecystokinin (CCK) and secretin in the IC treatment group were higher compared
      to the other treatment groups (p<0.05). In addition to the changes in CCK and
      secretin levels upon IC treatment, the pancreatic alpha-amylase activity in the
      duodenum was higher in the IC group compared to the control diet group (p<0.05).
      The response of serum ghrelin to IC and AHC treatment was in accordance with the
      response of serum secretin. The level of peptide fragments flowing in the
      duodenum was higher in the IC treatment group than the other treatment groups
      (p<0.05). In conclusion, this study demonstrated that an increase in duodenal CCK
      and secretin upon IC oral administration increased pancreatic alpha-amylase
      secretion. In addition, ghrelin may be associated with GI hormone secretion in
      Korean native steers. 

PMID- 25049836
TI  - Treated Olive Cake as a Non-forage Fiber Source for Growing Awassi Lambs: Effects
      on Nutrient Intake, Rumen and Urine pH, Performance, and Carcass Yield.
AB  - The objective of this study was to investigate the effects of partial replacement
      of wheat hay with sun-dried (SOC) or acid-treated SOC (ASOC) olive cake on
      nutrient intake and performance of Awassi lambs. An additional objective was to
      study the effects of acid treatment of olive cake (OC) on its chemical
      composition and nutritive value. On DM basis, sun-drying of OC did not
      dramatically affect its chemical composition. On the other hand, treating SOC
      with phosphoric acid decreased (p<0.05) SOC contents of neutral detergent fiber.
      Twenty seven male lambs (17.6+/-0.75 kg body weight) individually housed in
      shaded pens were randomly assigned to one of three dietary treatments (9
      lambs/treatment). Dietary treatments were formulated to be isocaloric and
      isonitrogenous by replacing 50% of wheat hay in the control diet (CTL) with SOC
      or ASOC and to meet all nutrient requirements. Dietary treatments had no effects
      on nutrient intake or digestibility except for ether extract. Lambs fed the SOC
      diet had (p = 0.05) faster growth rate, greater final body weight, and greater
      total body weight gain in comparison with the CTL diet, but not different from
      the ASOC diet. Additionally, lambs fed the SOC diet had greater (p = 0.03) hot
      and cold carcass weights than the ASOC diet, but not different from the CTL diet.
      However, feed conversion ratios and dressing percentages were similar among
      dietary treatments. In conclusion, replacing half of dietary wheat hay with SOC
      improved performance of Awassi lambs with no detrimental effects on nutrients
      intake or digestibility. No further improvements in the nutritive value of SOC
      and lambs performance were detected when SOC was treated with acid. 

PMID- 25049837
TI  - Effects of Dietary Supplementation with Hainanmycin on Protein Degradation and
      Populations of Ammonia-producing Bacteria In vitro.
AB  - An in vitro fermentation was conducted to determine the effects of hainanmycin on
      protein degradation and populations of ammonia-producing bacteria. The substrates
      (DM basis) for in vitro fermentation consisted of alfalfa hay (31.7%), Chinese
      wild rye grass hay (28.3%), ground corn grain (24.5%), soybean meal (15.5%) with
      a forage: concentrate of 60:40. Treatments were the control (no additive) and
      hainanmycin supplemented at 0.1 (H0.1), 1 (H1), 10 (H10), and 100 mg/kg (H100) of
      the substrates. After 24 h of fermentation, the highest addition level of
      hainanmycin decreased total VFA concentration and increased the final pH. The
      high addition level of hainanmycin (H1, H10, and H100) reduced (p<0.05) branched
      chain VFA concentration, the molar proportion of acetate and butyrate, and ratio
      of acetate to propionate; and increased the molar proportion of propionate,
      except that for H1 the in molar proportion of acetate and isobutyrate was not
      changed (p>0.05). After 24 h of fermentation, H10 and H100 increased (p<0.05)
      concentrations of peptide nitrogen and AA nitrogen and proteinase activity, and
      decreased (p<0.05) NH3-N concentration and deaminase activity compared with
      control. Peptidase activitives were not affected by hainanmycin. Hainanmycin
      supplementation only inhibited the growth of Butyrivibrio fibrisolvens, which is
      one of the species of low deaminative activity. Hainanmycin supplementation also
      decreased (p<0.05) relative population sizes of hyper-ammonia-producing species,
      except for H0.1 on Clostridium aminophilum. It was concluded that dietary
      supplementation with hainanmycin could improve ruminal fermentation and modify
      protein degradation by changing population size of ammonia-producing bacteria in
      vitro; and the addition level of 10 mg/kg appeared to achieve the best results. 

PMID- 25049838
TI  - Effects of supplemental levels of bazhen on growth performances, serum traits,
      immunity, meat quality and antioxidant activity of taiwan country chickens.
AB  - One hundred and sixty Taiwan country chickens (d-old chicks) were randomly
      assigned into four groups with four replicates and equal sex. Basal diets were
      supplemented with 0, 0.5, 1 and 2% of Bazhen powder, a traditional Chinese herbal
      medicine complex. The study was conducted for 14 wks. Experimental results
      indicated that Bazhen supplement did not influence feed intake, body weight gain
      and feed:gain ratio. Compared with control group, the percentage of serum HDL
      (high-density lipoprotein) linearly increased (p<0.03) and that of VLDL+LDL (very
      low-density+low-density lipoprotein) linearly decreased (p<0.03) in Bazhen
      supplemented groups, that 2% Bazhen was significantly different with control
      group (p<0.05). Chickens fed diets containing 2% Bazhen displayed reduced
      (p<0.05) serum GOT (glutamic-oxaloacetic transaminase) levels. The IgG, gamma
      globulin levels and PHA (phytohemagglutinin) skin challenge results in 1% Bazhan
      supplemented group were higher (p<0.05) than in the control group, the SRBC
      (sheep red blood cell) and ND (newcastle disease) titers in Bazhen supplemented
      groups were linear higher (p<0.05) than in the control group. The liver catalase
      activity and the capacity of scavenging DPPH (alpha-alpha-diphenyl-beta
      picrylhydrazyl) radical were linearly increased (p<0.03) in Bazhen supplemented
      groups, and the 1 and 2% groups were different from the control group (p<0.05).
      Liver TBARS (thiobarbituric acid-reactive substances) levels in all Bazhen
      supplemented groups and total glutathione level in the 2% group were reduced
      (p<0.05) compared to the control group and displayed a linear response (p<0.05).
      The TBA (thiobarbituric acid) and pH value of the breast muscle after 24 h post
      mortem in the Bazhen supplemented groups was linear lower (p<0.05) than in the
      control group. Results from this study demonstrated that Bazhen supplement in
      chicken had several beneficial effects, including increased SRBC and ND titers,
      HDL and IgG, gamma-globulin levels, PHA skin challenge result, decreased VLDL+LDL
      and GOT levels, and displayed antioxidation effects in serum and carcass meat
      parameters. 

PMID- 25049839
TI  - Effects of resveratrol and essential oils on growth performance, immunity,
      digestibility and fecal microbial shedding in challenged piglets.
AB  - A study was conducted to evaluate the effects of resveratrol and essential oils
      from medicinal plants on the growth performance, immunity, digestibility, and
      fecal microbial shedding of weaned piglets. A total of 48 weaned piglets (8 kg
      initial weight, 28-d-old) were randomly allotted to four dietary treatments with
      3 replications of 4 piglets each. The dietary treatments were NC (negative
      control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1
      (basal diet+0.2% resveratrol), and T2 (basal diet+0.0125% essential oil blend).
      All piglets were orally challenged with 5 ml culture fluid containing 2.3*10(8)
      cfu/ml of Escherichia coli KCTC 2571 and 5.9*10(8) cfu/ml Salmonella enterica
      serover Typhimurium. The PC group (p<0.05) showed the highest average daily gain
      (ADG) and average daily feed intake (ADFI) throughout the experimental period,
      although feed conversion ratio (FCR) was improved in the T1 group (p>0.05). Serum
      IgG level was increased in the T1 group, whereas TNF-alpha levels was reduced in
      the supplemented groups compared to control (p<0.05). The PC diet improved the
      dry matter (DM) digestibility, whereas PC and T2 diets improved nitrogen (N)
      digestibility compared to NC and T1 diets (p<0.05). Fecal Salmonella and E. coli
      counts were reduced in all treatment groups compared to control (p<0.05). Fecal
      Lactobacillus spp. count was increased in the T2 group compared to others
      (p<0.05). Dietary treatments had no significant effect on fecal Bacillus spp.
      count throughout the entire experimental period. Based on these results,
      resveratrol showed strong potential as antibiotic alternatives for reversing the
      adverse effects of weaning stress on growth performance, immunity and microbial
      environment in E. coli and Salmonella-challenged piglets. 

PMID- 25049840
TI  - The Metabolizable Energy Value, Standardized Ileal Digestibility of Amino Acids
      in Soybean Meal, Soy Protein Concentrate and Fermented Soybean Meal, and the
      Application of These Products in Early-weaned Piglets.
AB  - Three experiments were conducted to evaluate the metabolizable energy (ME) value,
      standardized ileal digestibility (SID) of amino acids (AA) of soybean meal (SBM),
      soy protein concentrate (SPC) and fermented soybean meal (FSBM), and the
      application of these products in early-weaned piglets. In Exp. 1, four barrows
      with initial body weight (BW) of 14.2+/-1.4 kg were used in a 4*4 Latin square
      design. The diet 1 contained corn as the only energy source. The other three
      diets replaced 25% of corn in diet 1 with one of the three soybean products, and
      the digestable energy (DE) and ME contents were determined by difference. In Exp.
      2, four barrows (initial BW of 18.2+/-1.5 kg) were fitted with ileal T-cannulas
      and allotted to a 4*4 Latin square design. Three cornstarch-based diets were
      formulated using each of the soybean products as the sole source of AA. A
      nitrogen-free diet was also formulated to measure endogenous losses of AA. In
      Exp. 3, ninety six piglets (initial BW of 5.6+/-0.9 kg) weaned at 21+/-2 d were
      blocked by weight and assigned to one of three treatments for a 21-d growth
      performance study. The control diet was based on corn and SBM, the two
      treatments' diets contained either 10% SPC or FSBM and were formulated to same
      SID lysine to ME ratio of 3.6 g/Mcal. The results showed that the ME content of
      SPC was greater than SBM (p<0.05). The SID of most AA in SPC was greater than the
      SID of AA in SBM (p<0.05). For the essential AA, the SID of histidine,
      isoleucine, leucine, lysine and threonine in FSBM were greater than in SBM
      (p<0.05). Even though they were fed same SID lysine to ME ratio of 3.6 g/Mcal
      diets, pigs fed SPC and FSBM diets had greater weight gain, G:F (p<0.05) and
      better fecal score (p<0.05) than pigs fed SBM diet. In conclusion, SPC showed a
      higher ME content and SID of AA than the SBM. SID of some essential AA in FSBM
      was higher than SBM and was similar with SPC. But the lower antigenic proteins
      and anti-nutritional factors content in SPC and FSBM may be the main factors
      affecting the performance of early-weaned piglets rather than the increased ME
      content and SID of AA. 

PMID- 25049841
TI  - Growth performance, plasma Fatty acids, villous height and crypt depth of
      preweaning piglets fed with medium chain triacylglycerol.
AB  - A study was conducted to investigate the effects of feeding medium chain
      triacylglycerol (MCT) on growth performance, plasma fatty acids, villus height
      and crypt depth in preweaning piglets. A total of 150 new born piglets were
      randomly assigned into one of three treatments: i) Control (no MCT); ii) MCT with
      milk (MCT+milk); iii) MCT without milk (MCT+fasting). Body weight, plasma fatty
      acid profiles, villus height and crypt depth were measured. Final BW for the
      Control and MCT+fasting was lower (p<0.05) than MCT+milk. The piglets fed with
      MCT regardless of milk provision or fasting had greater medium chain fatty acids
      (MCFA) than the Control. In contrast, the Control had greater long chain fatty
      acid (LCFA) and unsaturated fatty acid (USFA) than the MCT piglets. The piglets
      fed with MCT regardless of milk provision or fasting had higher villus height for
      the duodenum and jejunum after 6 h of feeding. Similar observations were found in
      piglets fed with MCT after 6 and 8 days of treatment. This study showed that
      feeding MCT to the piglets before weaning improved growth performance, with a
      greater concentration of MCT in blood plasma as energy source and a greater
      height of villus in duodenum, jejunum and ileum. 

PMID- 25049842
TI  - Influence of dietary fat source on growth performance responses and carcass
      traits of broiler chicks.
AB  - This study was conducted to determine the effects of three different fat sources
      and their combination on growth performance, carcass traits and intestinal
      measurements of broiler chickens reared to 42 d of age. Two hundred day-old male
      broiler chicks (Ross 308) were randomly assigned to one of five treatments with
      four replicates of 10 chicks based on a completely randomized design. The dietary
      treatments consisted of 4% added fat from three different sources and their
      combination as follows: T, diet containing 4% tallow; CO, diet containing 4%
      canola oil; SFO, diet containing 4% sunflower oil; TCO, diet containing 2%
      tallow+2% canola oil; TSFO, diet containing 2% tallow+2% sunflower oil. Dietary
      fat type affected significantly BW and gain as well as feed efficiency in birds
      fed the TCO diets compared with those fed the other diets. Dietary fat type also
      modified meat yield, resulting in a higher breast and drumstick yields in the
      birds fed TCO and TSFO diets, respectively. Most of internal organ relative
      weights and small intestine measurements were not influenced by dietary
      treatments, except for the abdominal fat pad weight that was lower in birds fed
      SFO and for small intestinal length that was influenced by fat source. Results
      from the current study suggested that the supplementation with a combination of
      vegetable and animal fat sources in broiler diet supported positively growth
      performance and carcass parameters. 

PMID- 25049843
TI  - Effect of restricted grazing time on the foraging behavior and movement of tan
      sheep grazed on desert steppe.
AB  - To investigate the effect of restricted grazing time on behavior of Tan sheep on
      desert steppe, forty 4-months old male Tan sheep with an original body weight
      (BW) of 15.62+/-0.33 kg were randomly allocated to 4 grazing groups which
      corresponded to 4 different restricted grazing time treatments of 2 h/d (G2), 4
      h/d (G4), 8 h/d (G8) and 12 h/d (G12) access to pasture. The restricted grazing
      times had a significant impact on intake time, resting time, ruminating time,
      bite rate and movement. As the grazing time decreased, the proportion of time
      spent on intake, bite rate and grazing velocity significantly (p<0.05) increased,
      but resting and ruminating time clearly (p<0.05) decreased. The grazing months
      mainly depicted effect on intake time and grazing velocity. In conclusion, by
      varying their foraging behavior, Tan sheep could improve grazing efficiency to
      adapt well to the time-limited grazing circumstance. 

PMID- 25049844
TI  - Variation of meat quality parameters due to conformation and fat class in
      limousin bulls slaughtered at 25 to 27 months of age.
AB  - The aim of the present study was to determine the influence of age of animal, hot
      carcass weight, pH, conformation and fat class on basic beef quality attributes
      (tenderness, sarcomere length, basic chemical composition, marbling and colour)
      in a group of purebred animals. The object of the study was beef of Limousin
      bulls (25 to 27 months, hot carcass weight - 432+/-31 kg, "U" conformation class,
      "2"-"3" fat class). Analysed cuts were Infraspinatus muscle from the blade and
      Longissimus dorsi muscle from the cube roll and the striploin. Tenderness was
      analysed with universal testing machine, colour - chromometer analysis, sarcomere
      length - microscopic method, basic chemical composition - near-infrared
      spectroscopy and marbling - computer image analysis. No differences in tenderness
      and sarcomere length were observed within the age groups of Limousin bulls (age
      of 25, 26, 27 months) (p>0.05). Moisture (p = 0.0123) and fat (p = 0.0250)
      content were significantly different for meat of animals slaughtered at the age
      of 25 and 27 months. No influence of pH value on tenderness was observed, but at
      the same time, influence on sarcomere length (p = 0.039) and b* component of
      colour (0.045) was found. For "U" conformation class, in subclasses, as well as
      for fat classes "2"-"3", there were no differences in tenderness, sarcomere
      length and colour components. Higher fat content was observed in the higher fat
      class, rather than in lower, however this feature was not associated with
      marbling. 

PMID- 25049845
TI  - Quality Assessment of Longissimus and Semitendinosus Muscles from Beef Cattle
      Subjected to Non-penetrative and Penetrative Percussive Stunning Methods.
AB  - This study provides a comparative analysis of the effects of pre-slaughter
      penetrative and non-penetrative stunning and post-slaughter stunning on meat
      quality attributes in longissimus lumborum (LL) and semitendinosus (ST) muscles
      in heifers. Ten animals were assigned to each of four treatment groups: i)
      animals were subjected to conventional Halal slaughter (a clean incision through
      the structures at the front of the upper neck - the trachea, oesophagus, carotid
      arteries and jugular veins) and post-cut penetrating mechanical stun within 10 to
      20 s of the neck cut (Unstunned; US); ii) high power non-penetrating mechanical
      stunning followed by the neck cut (HPNP); iii) low power non-penetrating
      mechanical stunning followed by the neck cut (LPNP); and iv) penetrative stunning
      using a captive bolt pistol followed by the neck cut (P). For each carcass,
      muscle samples were removed within 45 min of slaughter, portioned and analysed
      for pH, cooking loss, water holding capacity (WHC), tenderness (WBS), lipid
      oxidation (TBARS) and color, over a two week storage period. Stunning did not
      affect pH and cooking loss. Significant differences in water holding capacity,
      tenderness, lipid oxidation and color were present at different storage time
      points. HPNP stunning resulted in lower WHC and color values, particularly
      lightness (L*), higher TBARS values and peak force values compared with those
      stunned using LPNP, P and US. These adverse effects on quality were mostly
      encountered in the ST muscle. In conclusion, the meat quality achieved using P,
      LPNP and US treatments was comparable, and no treatment stood out as considerably
      better than another. 

PMID- 25049846
TI  - Flavour chemistry of chicken meat: a review.
AB  - Flavour comprises mainly of taste and aroma and is involved in consumers' meat
      buying behavior and preferences. Chicken meat flavour is supposed to be affected
      by a number of ante- and post-mortem factors, including breed, diet, post-mortem
      ageing, method of cooking, etc. Additionally, chicken meat is more susceptible to
      quality deterioration mainly due to lipid oxidation with resulting off-flavours.
      Therefore, the intent of this paper is to highlight the mechanisms and chemical
      compounds responsible for chicken meat flavour and off-flavour development to
      help producers in producing the most flavourful and consistent product possible.
      Chicken meat flavour is thermally derived and the Maillard reaction, thermal
      degradation of lipids, and interaction between these 2 reactions are mainly
      responsible for the generation of flavour and aroma compounds. The reaction of
      cysteine and sugar can lead to characteristic meat flavour specially for chicken
      and pork. Volatile compounds including 2-methyl-3-furanthiol, 2-furfurylthiol,
      methionol, 2,4,5-trimethyl-thiazole, nonanol, 2-trans-nonenal, and other
      compounds have been identified as important for the flavour of chicken. However 2
      methyl-3-furanthiol is considered as the most vital chemical compound for chicken
      flavour development. In addition, a large number of heterocyclic compounds are
      formed when higher temperature and low moisture conditions are used during
      certain cooking methods of chicken meat such as roasting, grilling, frying or
      pressure cooking compared to boiled chicken meat. Major volatile compounds
      responsible for fried chicken are 3,5-dimethyl-1,2,4-trithiolanes, 2,4,6
      trimethylperhydro-1,3,5-dithiazines, 3,5-diisobutyl-1,2,4-trithiolane, 3-methyl-5
      butyl-1,2,4-trithiolane, 3-methyl-5-pentyl-1,2,4-trithiolane, 2,4-decadienal and
      trans-4,5-epoxy-trans-2-decenal. Alkylpyrazines were reported in the flavours of
      fried chicken and roasted chicken but not in chicken broth. The main reason for
      flavour deterioration and formation of undesirable "warmed over flavour" in
      chicken meat products are supposed to be the lack of alpha-tocopherol in chicken
      meat. 

PMID- 25049847
TI  - Inbreeding and genetic diversity in three imported Swine breeds in china using
      pedigree data.
AB  - The accumulation of inbreeding and the loss of genetic diversity is a potential
      problem in the modern swine breeds in China. Therefore, the purpose of this study
      was to analyze the pedigrees of Chinese Duroc (CD), Landrace (CL) and Yorkshire
      (CY) swine to estimate the past and current rates of inbreeding, and to identify
      the main causes of genetic diversity loss. Pedigree files from CD, CL and CY
      containing, 4529, 16,776 and 22,600 records, respectively, were analyzed.
      Pedigree completeness indexes of the three breeds, accounting for one generation
      back, were 83.72, 93.93 and 93.59%, respectively. The estimated average annual
      inbreeding rates for CD, CL and CY in recent three years were 0.21, 0.19 and
      0.13%, respectively. The estimated average percentage of genetic diversity loss
      within each breed in recent three years was about 8.92, 2.19, and 3.36%,
      respectively. The average relative proportion of genetic diversity loss due to
      unequal contributions of founders in CD, CL and CY was 69.09, 57.95 and 60.57%,
      and due to random genetic drift was 30.91, 42.05 and 39.43%, respectively. The
      estimated current effective population size for CD, CL and CY was 76, 117 and
      202, respectively. Therefore, CD has been found to have lost considerable genetic
      diversity, demanding priority for optimizing the selection and mating to control
      future coancestry and inbreeding. Unequal contribution of founders was a major
      cause of genetic diversity loss in Chinese swine breeds and random genetic drift
      also showed substantial impact on the loss of diversity. 

PMID- 25049848
TI  - A SNP Harvester Analysis to Better Detect SNPs of CCDC158 Gene That Are
      Associated with Carcass Quality Traits in Hanwoo.
AB  - The purpose of this study was to investigate interaction effects of genes using a
      Harvester method. A sample of Korean cattle, Hanwoo (n = 476) was chosen from the
      National Livestock Research Institute of Korea that were sired by 50 Korean
      proven bulls. The steers were born between the spring of 1998 and the autumn of
      2002 and reared under a progeny-testing program at the Daekwanryeong and Namwon
      branches of NLRI. The steers were slaughtered at approximately 24 months of age
      and carcass quality traits were measured. A SNP Harvester method was applied with
      a support vector machine (SVM) to detect significant SNPs in the CCDC158 gene and
      interaction effects between the SNPs that were associated with average daily
      gains, cold carcass weight, longissimus dorsi muscle area, and marbling scores.
      The statistical significance of the major SNP combinations was evaluated with x
      (2)-statistics. The genotype combinations of three SNPs, g.34425+102 A>T(AA),
      g.4102636T>G(GT), and g.11614+19G>T(GG) had a greater effect than the rest of SNP
      combinations, e.g. 0.82 vs. 0.75 kg, 343 vs. 314 kg, 80.4 vs 74.7 cm(2), and 7.35
      vs. 5.01, for the four respective traits (p<0.001). Also, the estimates were
      greater compared with single SNPs analyzed (the greatest estimates were 0.76 kg,
      320 kg, 75.5 cm(2), and 5.31, respectively). This result suggests that the SNP
      Harvester method is a good option when multiple SNPs and interaction effects are
      tested. The significant SNPs could be applied to improve meat quality of Hanwoo
      via marker-assisted selection. 

PMID- 25049849
TI  - Linkage Disequilibrium Estimation of Chinese Beef Simmental Cattle Using High
      density SNP Panels.
AB  - Linkage disequilibrium (LD) plays an important role in genomic selection and
      mapping quantitative trait loci (QTL). In this study, the pattern of LD and
      effective population size (Ne ) were investigated in Chinese beef Simmental
      cattle. A total of 640 bulls were genotyped with IlluminaBovinSNP50BeadChip and
      IlluminaBovinHDBeadChip. We estimated LD for each autosomal chromosome at the
      distance between two random SNPs of <0 to 25 kb, 25 to 50 kb, 50 to 100 kb, 100
      to 500 kb, 0.5 to 1 Mb, 1 to 5 Mb and 5 to 10 Mb. The mean values of r(2) were
      0.30, 0.16 and 0.08, when the separation between SNPs ranged from 0 to 25 kb to
      50 to 100 kb and then to 0.5 to 1 Mb, respectively. The LD estimates decreased as
      the distance increased in SNP pairs, and increased with the increase of minor
      allelic frequency (MAF) and with the decrease of sample sizes. Estimates of
      effective population size for Chinese beef Simmental cattle decreased in the past
      generations and Ne was 73 at five generations ago. 

PMID- 25049850
TI  - Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with
      Carcass Traits in Korean Cattle.
AB  - The objective of this study was to investigate single nucleotide polymorphisms
      (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate
      whether these polymorphisms affect carcass traits in the Korean cattle
      population. We resequenced to detect SNPs from 24 unrelated individuals and
      identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter
      region. Of these 19 SNPs, four were selected for genotyping based on linkage
      disequilibrium (LD). We genotyped 429 steers to assess the associations of these
      four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and
      g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p =
      0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated
      with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four
      SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings
      suggest that polymorphisms in the NOV gene may be among the important genetic
      factors affecting carcass yield in beef cattle. 

PMID- 25049851
TI  - Comparison of alpha1-Antitrypsin, alpha1-Acid Glycoprotein, Fibrinogen and NOx as
      Indicator of Subclinical Mastitis in Riverine Buffalo (Bubalus bubalis).
AB  - Mastitis set apart as clinical and sub clinical is a disease complex of dairy
      cattle, with sub clinical being the most important economically. Of late,
      laboratories showed interest in developing biochemical markers to diagnose sub
      clinical mastitis (SCM) in herds. Many workers reported noteworthy alternation of
      acute phase proteins (APPs) and nitric oxide, (measured as nitrate+nitrite = NOx)
      in milk due to intra-mammary inflammation. But, the literature on validation of
      these parameters as indicators of SCM, particularly in riverine milch buffalo
      (Bubalus bubalis) milk is inadequate. Hence, the present study focused on
      comparing several APPs viz. alpha1- anti trypsin, alpha1- acid glycoprotein,
      fibrinogen and NOx as indicators of SCM in buffalo milk. These components in milk
      were estimated using standardized analytical protocols. Somatic cell count (SCC)
      was done microscopically. Microbial culture was done on 5% ovine blood agar. Of
      the 776 buffaloes (3,096 quarters) sampled, only 347 buffaloes comprising 496
      quarters were found positive for SCM i.e. milk culture showed growth in blood
      agar with SCC>=2*10(5) cells/ml of milk. The cultural examination revealed Gram
      positive bacteria as the most prevalent etiological agent. It was observed that
      alpha1- anti trypsin and NOx had a highly significant (p<0.01) increase in SCM
      milk, whereas, the increase of alpha1- acid glycoprotein in infected milk was
      significant (p<0.05). Fibrinogen was below detection level in both healthy and
      SCM milk. The percent sensitivity, specificity and accuracy, predictive values
      and likelihood ratios were calculated taking bacterial culture examination and
      SCC>=2*10(5) cells/ml of milk as the benchmark. Udder profile correlation
      coefficient was also used. Allowing for statistical and epidemiological analysis,
      it was concluded that alpha1- anti trypsin indicates SCM irrespective of
      etiology, whereas alpha1- acid glycoprotein better diagnosed SCM caused by gram
      positive bacteria. NOx did not prove to be a good indicator of SCM. It is
      recommended measuring both alpha1- anti trypsin and alpha1- acid glycoprotein in
      milk to diagnose SCM in buffalo irrespective of etiology. 

PMID- 25049852
TI  - Regulation of Interferon-stimulated Gene (ISG)12, ISG15, and MX1 and MX2 by
      Conceptus Interferons (IFNTs) in Bovine Uterine Epithelial Cells.
AB  - Various endometrial genes in ruminant ungulates are regulated by conceptus
      interferon tau (IFNT). However, the effect of each IFNT isoform has not been
      carefully evaluated. In this study, the effects of 2 IFNT isoforms, paralogs
      found in utero, and interferon alpha (IFNA) on uterine epithelial and Mardin
      Darby bovine kidney (MDBK) cells were evaluated. Expression vectors of the bovine
      interferon (bIFNT) genes bIFNT1, bIFNTc1, and bIFNA were constructed, and
      recombinant bIFNs (rbIFNs) were produced by 293 cells. Bovine uterine epithelial
      or MDBK cells were cultured in the presence or absence of increasing
      concentrations of each rbIFN for 24, 48, or 72 h. Transcript levels of the IFN
      stimulated genes (ISGs) ISG12, ISG15, MX1, and MX2 were analyzed using
      quantitative reverse transcription-polymerase chain reaction. These messenger
      RNAs were up-regulated by rbIFN in a time- and concentration-dependent manner. In
      the epithelial cells, the ISG12 transcript level increased at 48 h after rbIFN
      treatment but slightly decreased at 72 h, whereas the transcript level of ISG15
      increased at 24 h and was maintained through 72 h. Expressions of MX1 and MX2
      increased at 72 h after rbIFN treatment. MX1 expression increased in all
      treatment groups, but MX2 increased only by bIFNTc1. In MDBK cells, the
      expression of ISG12 was increased by bIFNT1 and bIFNTc1 after 24 and 72 h;
      however, it was unchanged by rbIFNA. ISG15 increased following the same pattern
      as that seen in uterine epithelial cells, and MX1 showed a similar expression
      pattern. MX2 expression was increased by bIFNTc1 treatment in uterine epithelial
      cells, and its expression was increased by both bIFNT1 and bIFNTc1 in MDBK cells.
      These results show that epithelial and MDBK cell responses to IFNs differ,
      suggesting that IFNs possess common functions, but may have acquired different
      functions following gene duplication. 

PMID- 25049853
TI  - Effect of gamma-Aminobutyric Acid (GABA) Producing Bacteria on In vitro Rumen
      Fermentation, Biogenic Amine Production and Anti-oxidation Using Corn Meal as
      Substrate.
AB  - The effects and significance of gamma-amino butyric acid (GABA) producing
      bacteria (GPB) on in vitro rumen fermentation and reduction of biogenic amines
      (histamine, methylamine, ethylamine, and tyramine) using corn meal as a substrate
      were determined. Ruminal samples collected from ruminally fistulated Holstein
      cows served as inoculum and corn was used as substrate at 2% dry matter (DM).
      Different inclusion rates of GPB and GABA were evaluated. After incubation,
      addition of GPB had no significant effect on in vitro fermentation pH and total
      gas production, but significantly increased the ammonia nitrogen (NH3-N)
      concentration and reduced the total biogenic amines production (p<0.05).
      Furthermore, antioxidation activity was improved as indicated by the
      significantly higher concentration of superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) among treated samples when compared to the control (p<0.05).
      Additionally, 0.2% GPB was established as the optimum inclusion level. Taken
      together, these results suggest the potential of utilizing GPB as feed additives
      to improve growth performance in ruminants by reducing biogenic amines and
      increasing anti-oxidation. 

PMID- 25049854
TI  - Growth performance of lambs fed diet supplemented with rice bran oil as such or
      as calcium soap.
AB  - Forty two Malpura lambs (21 d old) were divided into three groups of 14 each
      consisting of 8 females and 6 males. Lambs were allowed to suckle their
      respective dams twice daily up to weaning (13 wks) and offered free choice
      concentrate and roughage in a cafeteria system. The lambs in control group were
      fed conventional concentrate mixture, in RBO group concentrate mixture fortified
      with 4% industrial grade rice bran oil and in Ca-soap rice bran oil (as in RBO
      group) was supplemented in the form of calcium soap. The concentrate intake
      decreased(p<=0.05) in RBO group as a result total dry matter, crude protein and
      metabolizable energy intake decreased compared to control whereas Ca-soap
      prepared from the same rice bran oil stimulated the concentrate intake leading to
      higher total dry matter, crude protein and energy intakes. The digestibility of
      dry matter (p<=0.05), organic matter (p<=0.05) and crude protein (p<=0.05) was
      higher in RBO group followed by Ca-soap and control whereas no effect was
      observed for ether extract digestibility. Higher cholesterol (p<=0.05) content
      was recorded in serum of oil supplemented groups (RBO and Ca-soap) while no
      effect was recorded for other blood parameters. Rice bran oil as such adversely
      affected and reduced the body weight gain (p<=0.001) of lambs in comparison to
      control whereas the Ca-soap of rice bran oil improved body weight gain and feed
      conversion efficiency in lambs. Fat supplementation decreased total volatile
      fatty acids (p<=0.05) and individual volatile fatty acid concentration which
      increased at 4 h post feeding. Fat supplementation also reduced (p<=0.05) total
      protozoa count. Ca-soap of rice bran oil improved pre slaughter weight (p<=0.05)
      and hot carcass weight (p<=0.05). It is concluded from the study that rice bran
      oil in the form of calcium soap at 40 g/kg of concentrate improved growth, feed
      conversion efficiency and carcass quality as compared to rice bran oil as such
      and control groups. 

PMID- 25049855
TI  - Effect of plants containing secondary compounds with palm oil on feed intake,
      digestibility, microbial protein synthesis and microbial population in dairy
      cows.
AB  - The objective of this study was to determine the effect of rain tree pod meal
      with palm oil supplementation on feed intake, digestibility, microbial protein
      synthesis and microbial populations in dairy cows. Four, multiparous early
      lactation Holstein-Friesian crossbred (75%) lactating dairy cows with an initial
      body weight (BW) of 405+/-40 kg and 36+/-8 DIM were randomly assigned to receive
      dietary treatments according to a 4*4 Latin square design. The four dietary
      treatments were un-supplementation (control), supplementation with rain tree pod
      meal (RPM) at 60 g/kg, supplementation with palm oil (PO) at 20 g/kg, and
      supplementation with RPM at 60 g/kg and PO at 20 g/kg (RPO), of total dry matter
      intake. The cows were offered concentrates, at a ratio of concentrate to milk
      production of 1:2, and chopped 30 g/kg of urea treated rice straw was fed ad
      libitum. The RPM contained condensed tannins and crude saponins at 88 and 141
      g/kg of DM, respectively. It was found that supplementation with RPM and/or PO to
      dairy cows diets did not show negative effects on feed intake and ruminal pH and
      BUN at any times of sampling (p>0.05). However, RPM supplementation resulted in
      lower crude protein digestibility, NH3-N concentration and number of proteolytic
      bacteria. It resulted in greater allantoin absorption and microbial crude protein
      (p<0.05). In addition, dairy cows showed a higher efficiency of microbial N
      supply (EMNS) in both RPM and RPO treatments. Moreover, NDF digestibility and
      cellulolytic bacteria numbers were highest in RPO supplementation (p<0.05) while,
      supplementation with RPM and/or PO decreased the protozoa population in dairy
      cows. Based on this study, supplementation with RPM and/or PO in diets could
      improve fiber digestibility, microbial protein synthesis in terms of quantity and
      efficiency and microbial populations in dairy cows. 

PMID- 25049856
TI  - Effects of feeding levels of starter on weaning age, performance, nutrient
      digestibility and health parameters in holstein dairy calves.
AB  - To evaluate the effects of feeding four different levels of starter in male
      Holstein dairy calves, a completely randomized study was conducted, using 28
      calves with initial body weight of 40.5+/-2.4 kg. The animals were fed iso
      nitrogenous starter and were weaned when they consumed 350, 500, 650 and 800 g/d
      of starter for 3 d consecutively. Starter and water were available ad-libitum
      throughout the experiment. Body weight at pre-weaning (less than 5 wk) and post
      weaning (8 wk) was lower in calves that received 350 g/d of starter than in the
      other treatments (p<0.05). Feed conversion ratio (FCR) was the highest among all
      treatments in pre-weaning period (p<0.05). Dry matter intake (DMI) at weaning and
      total DMI was higher in that calves received 800 g/d of starter compared with
      other treatments (p<0.05). Calves fed 350 and 500 g/d of starter were weaned
      earlier (p<0.05) and showed lower milk consumption (kg, DM) compared with other
      treatments whereas no significant difference was observed between calves fed 350
      and 500 g/d of starter (p>0.05). Dry matter, organic matter and crude protein
      digestibilities were lower in calves that received 350 g/d of starter compared
      with other treatments (p<0.05). No differences were observed in acid detergent
      and neutral detergent fiber digestibility among all treatments
      (p>0.05).Treatments had no significant effect on time of starting rumination,
      respiratory score, and days of drug administration for pneumonia. There were no
      meaningful differences in feces, fecal odor scores, body temperature, and days of
      drug administration for diarrhea among all treatments (p>0.05). Total dry matter
      intake at the end of experiment showed no significant difference among calves fed
      600 and 800 g/d of starter, but calves fed 350 and 500 g/d of starter showed more
      dry matter (DM) intake than calves in the 600 and 800 g/d groups (p<0.05). 

PMID- 25049857
TI  - The Effects of Rhodobacter capsulatus KCTC-2583 on Cholesterol Metabolism, Egg
      Production and Quality Parameters during the Late Laying Periods in Hens.
AB  - An experiment was conducted to investigate the effects of dietary supplementation
      of Rhodobacter capsulatus KCTC-2583 on egg-yolk and serum cholesterol, egg
      production and quality parameters during the late laying periods in hens. A total
      of 160 Hy-Line Brown layers (54 wk-old) were randomly allotted to 4 treatment
      groups on the basis of laying performance. Each treatment had 4 replicates with
      10 birds each (40 birds per treatment). Two hens were confined individually with
      cage size 35*35*40 cm and each 10 birds (5 cages) shared a common feed trough
      between them forming one experimental unit. Dietary treatments were; basal diet
      supplemented with 0 (control), 0.05, 0.10 and 0.15% R. capsulatus KCTC-2583.
      Experimental diets were fed in meal form for 56 d. Dietary supplementation of
      increasing levels of R. capsulatus KCTC-2583 reduced (linear, p<0.05) egg-yolk
      cholesterol and triglycerides (d 28, 42 and 56) concentrations. Also, serum
      cholesterol and triglycerides (d 21, 42 and 56) concentrations were linearly
      reduced (p<0.05) with increasing dietary R. capsulatus KCTC-2583. Laying hens fed
      a diet supplemented with increasing levels of R. capsulatus KCTC-2583 had
      increased (linear; p<0.05) overall egg production, egg weight, egg mass and feed
      efficiency. However, dietary treatments had no effect (linear or quadratic;
      p>0.05) on feed intake of laying hens. At d 28 and 56, breaking strength and yolk
      colour of eggs were linearly improved (p<0.05) in laying hens fed dietary
      increasing levels of R. capsulatus KCTC-2583. Dietary treatment had no effects
      (linear or quadratic; p>0.05) on albumin height, shell thickness and shell weight
      at any period of experiment. These results indicate that dietary supplementation
      of R. capsulatus KCTC-2583 has the potential to improve the laying hen
      performance and lead to the development of low cholesterol eggs during late
      laying period in Hy-Line Brown hens. 

PMID- 25049858
TI  - Nitrogen-corrected True Metabolizable Energy and Amino Acid Digestibility of
      Chinese Corn Distillers Dried Grains with Solubles in Adult Cecectomized
      Roosters.
AB  - This study was conducted to evaluate chemical composition, nitrogen-corrected
      true metabolizable energy (TMEn) and true amino acids digestibility of corn
      distillers dried grains with solubles (DDGS) produced in China. Twenty five
      sources of corn DDGS was collected from 8 provinces of China. A precision-fed
      rooster assay was used to determine TMEn and amino acids digestibility with 35
      adult cecectomized roosters, in which each DDGS sample was tube fed (30 g). The
      average content of ash, crude protein, total amino acid, ether extract, crude
      fiber and neutral detergent fiber were 4.81, 27.91, 22.51, 15.22, 6.35 and
      37.58%, respectively. TMEn of DDGS ranged from 1,779 to 3,071 kcal/kg and
      averaged 2,517 kcal/kg. Coefficient of variation for non-amino acid crude
      protein, ether extract, crude fiber and TMEn were 55.0, 15.7, 15.9 and 17.1%,
      respectively. The average true amino acid digestibility was 77.32%. Stepwise
      regression analysis obtained the following equation: TMEn, kcal/kg = 
      2,995.6+0.88*gross energy+49.63*a* (BIC = 248.8; RMSE = 190.8; p<0.01). Removing
      gross energy from the model obtained the following equation: TMEn, kcal/kg =
      57.88*ether extracts+87.62*a* (BIC = 254.3, RMSE = 223.5; p<0.01). No correlation
      was found between color scores and lysine true digestibility (p>0.05). These
      results suggest that corn DDGS produced in China has a large variation in
      chemical composition, and gross energy and a* value can be used to generate TMEn
      predict equation. 

PMID- 25049859
TI  - Growth Performance, Carcass Characteristics and Plasma Mineral Chemistry as
      Affected by Dietary Chloride and Chloride Salts Fed to Broiler Chickens Reared
      under Phase Feeding System.
AB  - Requirements of dietary chloride (dCl) and chloride salts were determined by
      using 4*2 factorial arrangement under four phase feeding program. Four levels
      (0.31, 0.45, 0.59 and 0.73%) and two sources (NH4Cl and CaCl2) of the dCl were
      allocated to 1,472 chicks in eight dietary treatments in which each treatment was
      replicated four times with 46 birds per replicate. The four phase feeding program
      was comprised of four dietary phases: Prestarter (d 1 to 10), Starter (d 11 to
      20), Grower (d 21 to 33) and Finisher (d 34 to 42); and diets were separately
      prepared for each phase. The cations, anions, pH, dissolved oxygen (DO),
      temperature, electrical conductivity (EC), total dissolved solids (TDS) and
      salinity were analyzed in drinking water and were not affected by dietary
      treatments. BW gain (BWG; p<=0.009) and feed:gain (FG; p<=0.03) were improved in
      CaCl2 supplemented diets during d 1 to 10. The maximum response of BWG and FG was
      observed at 0.38% and 0.42% dCl, respectively, for d 34 to 42. However, the level
      of dCl for BWG during d 21 to 33 (p<=0.04) and d 34 to 42 (p<=0.009) was
      optimized at 0.60% and 0.42%, respectively. The level of dCl for optimized feed
      intake (FI; p<=0.006), FG (p<=0.007) and litter moisture (LM; p<=0.001) was
      observed at 0.60%, 0.38% and 0.73%, respectively, for d 1 to 42. Water intake
      (DWI) was not affected by increasing dCl supplementation (p>0.05); however, the
      ratio between DWI and FI (DWI:FI) was found highest at 0.73% dCl during d 1 to 10
      (p<=0.05) and d 21 to 33 (p<=0.009). Except for d 34 to 42 (p<=0.006), the
      increasing level of dCl did not result in a significant difference in mortality
      during any phase. Blood pH and glucose, and breast and thigh weights (percentage
      of dressed weight) were improved while dressing percentage (DP) and
      gastrointestinal health were exacerbated with NH4Cl as compared to CaCl2
      supplemented diets (p<=0.001). Higher plasma Na(+) and HCO3 (-) and lower Cl(-)
      and Ca(++) were observed in NH4Cl supplemented diets (p<=0.001). Increasing
      supplementation of dCl increased plasma Cl(-) (p<=0.04; quadratically) and
      linearly reduced plasma K(+) (p<=0.001), Ca(++) (p<=0.003), HCO3 (-) (p<=0.001),
      and Na(+) (p<=0.001; quadratically). Consequently, higher requirements of dietary
      chloride are suggested for feed intake; nevertheless, lower levels of dietary
      chloride are sufficient to support optimal BWG and FG with increasing age. The
      NH4Cl supplemented diets ameliorate breast and thigh meat yield along with
      overall energy balance (glucose). 

PMID- 25049860
TI  - Saccharomyces cerevisiae Live Cells Decreased In vitro Methane Production in
      Intestinal Content of Pigs.
AB  - An in vitro gas production technique was used in this study to elucidate the
      effect of two strains of active live yeast on methane (CH4) production in the
      large intestinal content of pigs to provide an insight to whether active live
      yeast could suppress CH4 production in the hindgut of pigs. Treatments used in
      this study include blank (no substrate and no live yeast cells), control (no live
      yeast cells) and yeast (YST) supplementation groups (supplemented with live yeast
      cells, YST1 or YST2). The yeast cultures contained 1.8*10(10) cells per g, which
      were added at the rates of 0.2 mg and 0.4 mg per ml of the fermented inoculum.
      Large intestinal contents were collected from 2 Duroc*Landrace*Yorkshire pigs,
      mixed with a phosphate buffer (1:2), and incubated anaerobically at 39 degrees C
      for 24 h using 500 mg substrate (dry matter (DM) basis). Total gas and CH4
      production decreased (p<0.05) with supplementation of yeast. The methane
      production reduction potential (MRP) was calculated by assuming net methane
      concentration for the control as 100%. The MRP of yeast 2 was more than 25%.
      Compared with the control group, in vitro DM digestibility (IVDMD) and total
      volatile fatty acids (VFA) concentration increased (p<0.05) in 0.4 mg/ml YST1 and
      0.2 mg/ml YST2 supplementation groups. Proportion of propionate, butyrate and
      valerate increased (p<0.05), but that of acetate decreased (p<0.05), which led to
      a decreased (p<0.05) acetate: propionate (A: P) ratio in the both YST2 treatments
      and the 0.4 mg/ml YST 1 supplementation groups. Hydrogen recovery decreased
      (p<0.05) with yeast supplementation. Quantity of methanogenic archaea per
      milliliter of inoculum decreased (p<0.05) with yeast supplementation after 24 h
      of incubation. Our results suggest that live yeast cells suppressed in vitro CH4
      production when inoculated into the large intestinal contents of pigs and shifted
      the fermentation pattern to favor propionate production together with an
      increased population of acetogenic bacteria, both of which serve as a competitive
      pathway for the available H2 resulting in the reduction of methanogenic archaea. 

PMID- 25049861
TI  - Validation and recommendation of methods to measure biogas production potential
      of animal manure.
AB  - In developing countries, biogas energy production is seen as a technology that
      can provide clean energy in poor regions and reduce pollution caused by animal
      manure. Laboratories in these countries have little access to advanced gas
      measuring equipment, which may limit research aimed at improving local adapted
      biogas production. They may also be unable to produce valid estimates of an
      international standard that can be used for articles published in international
      peer-reviewed science journals. This study tested and validated methods for
      measuring total biogas and methane (CH4) production using batch fermentation and
      for characterizing the biomass. The biochemical methane potential (BMP) (CH4 NL
      kg(-1) VS) of pig manure, cow manure and cellulose determined with the Moller and
      VDI methods was not significantly different in this test (p>0.05). The
      biodegradability using a ratio of BMP and theoretical BMP (TBMP) was slightly
      higher using the Hansen method, but differences were not significant. Degradation
      rate assessed by methane formation rate showed wide variation within the batch
      method tested. The first-order kinetics constant k for the cumulative methane
      production curve was highest when two animal manures were fermented using the VDI
      4630 method, indicating that this method was able to reach steady conditions in a
      shorter time, reducing fermentation duration. In precision tests, the
      repeatability of the relative standard deviation (RSDr) for all batch methods was
      very low (4.8 to 8.1%), while the reproducibility of the relative standard
      deviation (RSDR) varied widely, from 7.3 to 19.8%. In determination of biomethane
      concentration, the values obtained using the liquid replacement method (LRM) were
      comparable to those obtained using gas chromatography (GC). This indicates that
      the LRM method could be used to determine biomethane concentration in biogas in
      laboratories with limited access to GC. 

PMID- 25049862
TI  - Changes in Blood Constituents of Rabbits Subjected to Transportation under Hot,
      Humid Tropical Conditions.
AB  - Unlike Europe (particularly, Italy and Spain), where a number of studies have
      been conducted on the stressful effects of transport on rabbit welfare, few
      studies have been conducted on transportation of rabbits under hot, humid
      tropical conditions experienced in countries like Malaysia. We studied the
      effects of transportation in hot humid tropical conditions of Malaysia on
      physiometabolic changes in New Zealand white rabbits. Eighty experimental animals
      were divided into two groups of 40 bucks each and transported for either 3 or 1
      h. Transportation caused a significant upsurge of aspartate aminotransferase,
      alanine aminotransferase and creatine kinase activities (p<0.001) though did not
      significantly affect lactate dehydrogenase (LDH) activity (p = 0.0706). Both
      transportation periods caused elevation in plasma glucose levels, lactic acidosis
      and dehydration as evidenced through elevated packed cell volume and plasma
      protein concentration. It was concluded that regardless of the duration,
      transport of rabbits under hot humid tropical conditions, resulted in heat
      distress since the rabbits showed hyperglycemia, hypercalcemia, lactacidemia,
      lymphocytopenia, dehydration and increase in blood enzyme activities. 

PMID- 25049863
TI  - Effects of Short-term Feeding Magnesium before Slaughter on Blood Metabolites and
      Postmortem Muscle Traits of Halothane-carrier Pigs.
AB  - Fifty-four, mixed-sex, halothane-carrier crossbred (Yorkshire*Landrace) pigs with
      an average initial BW of 108.2+/-0.8 kg were randomly allotted to one of three
      dietary treatments for 5 d before slaughter: i) a control corn-soybean meal
      finisher diet devoid of supplemental magnesium; ii) a diet supplemented with 1.5
      g/kg of elemental Mg from magnesium acetate; and iii) a diet supplemented with
      1.5 g/kg of elemental Mg from magnesium sulfate heptahydrate. Serum creatine
      kinase (CK), lactate and glucose were analyzed at slaughter. Muscles from
      longissimus (LM) were packaged and stored to simulate display storage for muscle
      lactate and glycogen determinations at 0, 1, 2, 3, and 4 d. Mg supplementation
      reduced (p<0.05) serum CK and lactate concentration, but had no effect (p>0.05)
      on serum glucose. Daily change of muscle lactate concentration linearly increased
      (p<0.01), while glucose concentration linearly decreased (p<0.05) as storage time
      increased in all treatments. However, dietary Mg acetate and Mg sulfate
      supplementation in pigs elevated (p<0.05) muscle glycogen and reduced (p<0.05)
      muscle lactate concentrations, especially during the first 2 d of display,
      compared with pigs fed the control diet. This study suggests that short-term
      feeding of magnesium acetate and magnesium sulfate to heterozygous carriers of
      the halothane gene has beneficial effects on stress response and pork quality by
      improving blood and muscle biochemical indexes. 

PMID- 25049864
TI  - Guava (Psidium guajava L.) Powder as an Antioxidant Dietary Fibre in Sheep Meat
      Nuggets.
AB  - This study was conducted to explore the antioxidant potential and functional
      value of guava (Psidium guajava L.) powder in muscle foods. Guava powder was used
      as a source of antioxidant dietary fibre in sheep meat nuggets at two different
      levels i.e., 0.5% (Treatment I) and 1.0% (Treatment II) and its effect was
      evaluated against control. Guava powder is rich in dietary fibre (43.21%),
      phenolics (44.04 mg GAE/g) and possesses good radical scavenging activity as well
      as reducing power. Incorporation of guava powder resulted in significant decrease
      (p<0.05) in pH of emulsion and nuggets, emulsion stability, cooking yield and
      moisture content of nuggets while ash and moisture content of emulsion were
      increased. Total phenolics, total dietary fibre (TDF) and ash content
      significantly increased (p<0.05) in nuggets with added guava powder. Product
      redness value was significantly improved (p<0.05) due to guava powder. Textural
      properties did not differ significantly except, springiness and shear force
      values. Guava powder was found to retard lipid peroxidation of cooked sheep meat
      nuggets as measured by TBARS number during refrigerated storage. Guava powder did
      not affect sensory characteristics of the products and can be used as source of
      antioxidant dietary fibre in meat foods. 

PMID- 25049865
TI  - Effect of cattle breeds on milk composition and technological characteristics in
      china.
AB  - Cattle breeds have a striking effect on milk, including milk composition and
      technological characteristics. This study aims to compare milk composition,
      acidification activity, viscosity, milk dispersion system stability and casein
      molecular weight among three buffalo breeds in China. The technological
      characteristics of milk produced by three cattle breeds of river buffalo
      (Murrah), crossbreed 1st generation (F1), crossbreed multiple generation (FH,
      H>=3) buffaloes were investigated. Cattle breeds showed evident effect on milk
      protein, fat and total solids content, but little effect on most of buffalo
      casein molecular weight. Milk fat, protein content and the viscosity of buffalo
      milk from river buffalo were lower than those of F1 and FH, so was the buffer
      capacity. The viscosity was negatively correlated to temperature and
      concentration. Results of stability coefficient showed that milk dispersion
      system had the best dynamic stability characteristics under pH 6.6 and 6 times
      dilution, while zeta potential of Murrah milk was slightly higher than that of
      hybrid offspring (F1, FH). SDS-PAGE results showed that buffalo alphas-casein had
      a slightly faster mobility than standard alphas-casein; while buffalo beta-casein
      showed a slightly slower mobility than standard beta-casein. There is no clear
      differences in molecular weight of alphas-, beta-, and kappa-casein among Murrah,
      F1 and FH. 

PMID- 25049866
TI  - Comparison and correlation analysis of different Swine breeds meat quality.
AB  - This study was performed to determine the influence of pig breed and gender on
      the ultimate pH and physicochemical properties of pork. The correlations between
      pH and pork quality traits directly related to carcass grade, and consumer's
      preference were also evaluated. The pH and meat grading scores for cold carcasses
      of 215 purebred pigs (Duroc, Landrace, and Yorkshire) from four different farms
      were obtained. Meat quality parameters of the pork loin were analyzed. Duroc and
      female animals were more affected compared to other breeds and male pigs. Duroc
      animals had the highest ultimate pH, carcass back fat thickness, marbling scores,
      yellowness, and fat content (p<0.05). Landrace pigs had the highest color
      lightness and cooking loss values (p<0.05). Among all trait parameters, marbling
      scores showed the highest significant differences when evaluating the impact of
      breed and gender on meat quality characteristics (p<0.001). Ultimate pH was
      positively correlated with carcass weight (0.20), back fat thickness (0.19),
      marbling score (0.17), and color score (0.16) while negatively correlated with
      cooking loss (-0.24) and shear force (-0.20). Therefore, pork samples with lower
      ultimate pH had lower cooking loss, higher lightness, and higher shear force
      values irrespective of breed. 

PMID- 25049867
TI  - Effects of CSN1S2 Genotypes on Economic Traits in Chinese Dairy Goats.
AB  - The aim of this study was to investigate allele frequencies at the CSN1S2 locus
      in two Chinese dairy goat breeds and the effects of its variation on dairy goat
      economic traits. Seven hundred and eight goats from Xinong Saanen (XS, n = 268)
      and Guanzhong (GZ, N = 440) breeds were selected. The milk samples of 268 XS
      goats were collected during the middle of lactation, body size parameters (708
      goats) and daily milk yield (202 goats) were registered. The RFLP (restriction
      fragment length polymorphism) and SSCP (single strand conformation polymorphism)
      were used to detect the polymorphisms in CSN1S2. The Hardy-Weinberg (HW)
      equilibrium and the associations between body size, milk yield and composition
      and the genotypes were calculated. The results revealed that only A and F CSN1S2
      alleles were found in the two Chinese dairy goat breeds. Allelic frequencies of A
      and F were 0.795, 0.205 and 0.739, 0.261 in Xinong Saanen and Guanzhong
      population respectively. Xinong Saanen breed was in Hardy-Weinberg equilibrium,
      while Guanzhong breed deviated from Hardy-Weinberg equilibrium (p<0.05). The
      association of polymorphism with economic traits indicated that the goats with FF
      genotype have higher milk fat and total solid concentration than those with AA
      and AF genotypes (p<0.05). 

PMID- 25049868
TI  - Development of Genetic Markers for Triploid Verification of the Pacific Oyster,
      Crassostrea gigas.
AB  - The triploid Pacific oyster, which is produced by mating tetraploid and diploid
      oysters, is favored by the aquaculture industry because of its better flavor and
      firmer texture, particularly during the summer. However, tetraploid oyster
      production is not feasible in all oysters; the development of tetraploid oysters
      is ongoing in some oyster species. Thus, a method for ploidy verification is
      necessary for this endeavor, in addition to ploidy verification in aquaculture
      farms and in the natural environment. In this study, a method for ploidy
      verification of triploid and diploid oysters was developed using multiplex
      polymerase chain reaction (PCR) panels containing primers for molecular
      microsatellite markers. Two microsatellite multiplex PCR panels consisting of
      three markers each were developed using previously developed microsatellite
      markers that were optimized for performance. Both panels were able to verify the
      ploidy levels of 30 triploid oysters with 100% accuracy, illustrating the utility
      of microsatellite markers as a tool for verifying the ploidy of individual
      oysters. 

PMID- 25049869
TI  - Gene expression profiling in the pituitary gland of laying period and ceased
      period huoyan geese.
AB  - Huoyan goose is a Chinese local breed famous for its higher laying performance,
      but the problems of variety degeneration have emerged recently, especially a
      decrease in the number of eggs laid. In order to better understand the molecular
      mechanism that underlies egg laying in Huoyan geese, gene profiles in the
      pituitary gland of Huoyan geese taken during the laying period and ceased period
      were investigated using the suppression subtractive hybridization (SSH) method.
      Total RNA was extracted from pituitary glands of ceased period and laying period
      geese. The cDNA in the pituitary glands of ceased geese was subtracted from the
      cDNA in the pituitary glands of laying geese (forward subtraction); the reverse
      subtraction was also performed. After sequencing and annotation, a total of 30
      and 24 up and down-regulated genes were obtained from the forward and reverse SSH
      libraries, respectively. These genes mostly related to biosynthetic process,
      cellular nitrogen compound metabolic process, transport, cell differentiation,
      cellular protein modification process, signal transduction, small molecule
      metabolic process. Furthermore, eleven genes were selected for further analyses
      by quantitative real-time PCR (qRT-PCR). The qRT-PCR results for the most part
      were consistent with the SSH results. Among these genes, Synaptotagmin-1 (SYT1)
      and Stathmin-2 (STMN2) were substantially over-expressed in laying period
      compared to ceased period. These results could serve as an important reference
      for elucidating the molecular mechanism of higher laying performance in Huoyan
      geese. 

PMID- 25049870
TI  - Maternal Effects of Japanese Shorthorn Cows on the Growth of Embryo-transferred
      Japanese Black Calves in a Cow-calf Grazing System.
AB  - The growth performance of embryo-transferred Japanese Black calves that were born
      from, and suckled by, Japanese Shorthorn cows in a cow-calf grazing system (BS
      group, n = 5) was compared to that of Japanese Black calves from Japanese Black
      cows in a cowshed (BB-group, n = 5). The daily weight gain from birth to 1 month
      was higher in the BS-group than in the BB-group (p<0.01), and the same trend
      (p<0.05) was observed at 2 and 3 months of age. This resulted in body weight that
      was significantly higher for the BS-group between 1 and 3 months of age than what
      was observed for the BB-group (p<0.05). Heart girth was significantly greater in
      the BS-group than in the BB-group throughout the experimental period (p<0.01),
      and chest depth and withers height in the BS-group were significantly greater
      from 2 to 4 months of age (p<0.05) and at 4 months of age only (p<0.05). No
      difference in body length (p>0.05) was observed between the groups. These results
      suggest that the maternal effect of Japanese Shorthorn cows was positive for
      embryo-transferred Japanese Black calf growth during the early suckling stage. As
      Japanese Black calves are traded at a high price on the Japanese market, we
      conclude that this proposed production system is likely to improve the
      profitability of herd management in upland Japan. 

PMID- 25049872
TI  - Development of appropriate fibrolytic enzyme combination for maize stover and its
      effect on rumen fermentation in sheep.
AB  - In vitro studies were undertaken to develop an appropriate fibrolytic enzymes
      cocktail comprising of cellulase, xylanase and beta-D-glucanase for maize stover
      with an aim to increase its nutrient utilization in sheep. Cellulase and xylanase
      added individually to ground maize stover at an increasing dose rates (0, 100,
      200, 400, 800, 1,600, 3,200, 6,400, 12,800, 25,600, 32,000, 38,400, and 44,800
      IU/g DM), increased (p<0.01) the in vitro dry matter digestibility and in vitro
      sugar release. The doses selected for studying the combination effect of enzymes
      were 6,400 to 32,000 IU/g of cellulase and 12,800 to 44,800 IU/g of xylanase. At
      cellulase concentration of 6,400 IU/g, IVDMD % was higher (p<0.01) at higher
      xylanase doses (25,600 to 44,800 IU/g). While at cellulase doses (12,800 to
      32,000 IU/g), IVDMD % was higher at lower xylanase doses (12,800 and 25,600 IU/g)
      compared to higher xylanase doses (32,000 to 44,800 IU/g). At cellulase
      concentration of the 6,400 to 32,000 IU/g, the amount of sugar released increased
      (p<0.01) with increasing levels of xylanase concentrations except for the
      concentration of 44,800 IU/g. No effect of beta-D-glucanase (100 to 300 IU/g) was
      observed at lower cellulase-xylanase dose (cellulase-xylanase 12,800 to 12,800
      IU/g). Based on the IVDMD, the enzyme combination cellulase-xylanase 12,800 to
      12,800 IU/g was selected to study its effect on feed intake and rumen
      fermentation pattern, conducted on 12 rams (6 to 8 months; 20.34+/-2.369 kg body
      weight) fed 50% maize stover based TMR. The total volatile fatty acids (p<0.01)
      and ammonia-N concentration was higher in enzyme supplemented group, while no
      effect was observed on dry matter intake, ruminal pH and total nitrogen
      concentration. 

PMID- 25049871
TI  - The effects of thyme and cinnamon essential oils on performance, rumen
      fermentation and blood metabolites in holstein calves consuming high concentrate
      diet.
AB  - Essential oils have been shown to favorably effect in vitro ruminal fermentation,
      but there are few in vivo studies that have examined animal responses. The
      objective of this study was to evaluate the effects of thyme (THY) and cinnamon
      (CIN) essential oils on feed intake, growth performance, ruminal fermentation and
      blood metabolites in feedlot calves fed high-concentrate diets. Twelve growing
      Holstein calves (213+/-17 kg initial BW) were used in a completely randomized
      design and received their respective dietary treatments for 45 d. Treatments
      were: 1-control (no additive), 2-THY (5 g/d/calf) and 3-CIN (5 g/d/calf). Calves
      were fed ad libitum diets consisting of 15% forage and 85% concentrate, and
      adapted to the finishing diet by gradually increasing the concentrate ratio with
      feeding a series of transition diets 5 wk before the experiment started.
      Supplementation of THY or CIN did not affect DMI and ADG, and feed efficiency was
      similar between treatment groups. There were no effects of additives on ruminal
      pH and rumen concentrations of ammonia nitrogen and total VFA; whereas molar
      proportion of acetate and ratio of acetate to propionate decreased, and the molar
      proportion of propionate increased with THY and CIN supplementation. Rumen molar
      concentration of butyrate was significantly increased by adding CIN compared to
      control; but no change was observed with THY compared with control group. No
      effects of THY, or CIN were observed on valerate, isobutyrate or isovalerate
      proportions. Plasma concentrations of glucose, cholesterol, triglyceride, urea-N,
      beta-hydroxybutyrate, alanine aminotransferase and aspartate aminotransferase
      were not changed by feeding THY or CIN. Results from this study suggest that
      supplementing a feedlot finishing diet with THY or CIN essential oil might be
      useful as ruminal fermentation modifiers in beef production systems, but has
      minor impacts on blood metabolites. 

PMID- 25049873
TI  - Effect of carbohydrate source and cottonseed meal level in the concentrate on
      feed intake, nutrient digestibility, rumen fermentation and microbial protein
      synthesis in swamp buffaloes.
AB  - The objective of this study was to investigate the effect of carbohydrate source
      and cottonseed meal level in the concentrate on feed intake, nutrient
      digestibility, rumen fermentation and microbial protein synthesis in swamp
      buffaloes. Four, 4-yr old rumen fistulated swamp buffaloes were randomly assigned
      to receive four dietary treatments according to a 2*2 factorial arrangement in a
      4*4 Latin square design. Factor A was carbohydrate source; cassava chip (CC) and
      CC+rice bran at a ratio 3:1 (CR3:1), and factor B was level of cottonseed meal
      (CM); 109 g CP/kg (LCM) and 328 g CP/kg (HCM) in isonitrogenous diets (490 g
      CP/kg). Buffaloes received urea-treated rice straw ad libitum and supplemented
      with 5 g concentrate/kg BW. It was found that carbohydrate source did not affect
      feed intake, nutrient intake, digested nutrients, nutrient digestibility, ammonia
      nitrogen concentration, fungi and bacterial populations, or microbial protein
      synthesis (p>0.05). Ruminal pH at 6 h after feeding and the population of
      protozoa at 4 h after feeding were higher when buffalo were fed with CC than in
      the CR3:1 treatment (p<0.05). Buffalo fed with HCM had a lower roughage intake,
      nutrient intake, population of total viable and cellulolytic bacteria and
      microbial nitrogen supply than the LCM fed group (p<0.05). However, nutrient
      digestibility, ruminal pH, ammonia concentration, population of protozoa and
      fungi, and efficiency of microbial protein synthesis were not affected by
      cottonseed meal levels (p>0.05). Based on this experiment, concentrate with a low
      level of cottonseed meal could be fed with cassava chips as an energy source in
      swamp buffalo receiving rice straw. 

PMID- 25049874
TI  - Evaluation of coarsely ground wheat as a replacement for ground corn in the diets
      of lactating dairy cows.
AB  - Eight multiparous Holstein cows (569+/-47 kg of BW; 84+/-17 DIM) were used to
      evaluate the effects of different levels of coarsely ground wheat (CGW) as
      replacements for ground corn (GC) in diets on feed intake and digestion, ruminal
      fermentation, lactation performance, and plasma metabolites profiles in dairy
      cows. The cows were settled in a replicated 4*4 Latin square design with 3-wk
      treatment periods; four cows in one of the replicates were fitted with rumen
      cannulas. The four diets contained 0, 9.6, 19.2, and 28.8% CGW and 27.9, 19.2,
      9.6, and 0% GC on dry matter (DM) basis, respectively. Increasing dietary levels
      of CGW, daily DM intake tended to increase quadratically (p = 0.07); however,
      apparent digestibility of neutral detergent fiber (NDF) and acid detergent fiber
      (ADF) were significantly decreased (p<0.01) in cows fed the 28.8% CGW diets.
      Ruminal pH remained in the normal physiological range for all dietary treatments
      at all times, except for the 28.8% CGW diets at 6 h after feeding; moreover,
      increasing dietary levels of CGW, the daily mean ruminal pH decreased linearly (p
      = 0.01). Increasing the dietary levels of CGW resulted in a linear increase in
      ruminal propionate (p<0.01) and ammonia nitrogen (NH3-N) (p = 0.06)
      concentration, while ruminal acetate: propionate decreased linearly (p = 0.03) in
      cows fed the 28.8% CGW diets. Milk production was not affected by diets; however,
      percentage and yield of milk fat decreased linearly (p = 0.02) when the level of
      CGW was increased. With increasing levels of dietary CGW, concentrations of
      plasma beta-hydroxybutyric acid (BHBA) (p = 0.07) and cholesterol (p<0.01)
      decreased linearly, whereas plasma glucose (p = 0.08), insulin (p = 0.02) and
      urea nitrogen (p = 0.02) increased linearly at 6 h after the morning feeding. Our
      results indicate that CGW is a suitable substitute for GC in the diets of dairy
      cows and that it may be included up to a level of 19.2% of DM without adverse
      effects on feed intake and digestion, ruminal fermentation, lactation
      performance, and plasma metabolites if the cows are fed fiber-sufficient diets. 

PMID- 25049875
TI  - Use of dried stoned olive pomace in the feeding of lactating buffaloes: effect on
      the quantity and quality of the milk produced.
AB  - Dried stoned olive pomace (DSOP) was administered to dairy water buffaloes, and
      their productive performance and milk composition were analysed. Sixteen
      pluriparous lactating buffaloes were divided into two uniform groups (control and
      experimental), taking into consideration the following parameters: milk
      production (2,192 and 2,102 kg) and duration of lactation (254 and 252 d) of the
      previous year, distance from calving (51 and 43 d), milk production (9.71 and
      10.18 kg/d), body condition score (BCS) (6.44 and 6.31) and weight (617 and 653
      kg) at the beginning of the trial. Both diets had the same formulation: second
      cut alfalfa hay 20%, corn silage 42%, concentrate 38% but the two concentrates
      differed in their formulation, the experimental one contained 15.50% of DSOP as
      fed. The employed DSOP showed high amounts of secoiridoids, such as 3,4
      dihydroxyphenylethanol (3,4-DHPEA) (1.2 g/kg DM), 3,4-dihydroxyphenylethanol
      elenolic acid di-aldehyde (3,4-DHPEA-EDA) (12.6 g/kg DM), p-hydroxyphenylethanol
      elenolic acid di-aldehyde (p-HPEA-EDA) (5.6 g/kg DM) and lignans, which are known
      to be powerful bioactive compounds. The control diet had an energy-protein
      content of 0.86 Milk FU/kg DM and 143.3 g/kg DM of crude protein, whereas the
      experimental diet of 0.87 Milk FU/kg DM and 146.6 g/kg DM of crude protein. Each
      animal of the two groups received 17 kg DM/d and each buffalo of the experimental
      group, by way of the concentrate, ingested 1.05 kg DM/d of DSOP. The trial lasted
      40 days. No significant difference was found between the BCS (6.41 and 6.53),
      live weight (625.93 and 662.50 kg) and milk production (9.69 and 10.08 kg/d) of
      the two groups, as was the case for fat, protein, lactose, pH and coagulating
      parameters of the two milks. The milk fat of the experimental group had a
      significantly higher content of total tocopherols (10.45 vs 8.60 MUg/g, p<0.01)
      and retinol (3.17 vs 2.54 MUg/g, p<0.01). The content of the reactive substances
      with tiobarbituric acid (TBARs) was significantly lower in the milk fat of the
      experimental group (12.09 vs 15.05 MUg MDA/g, p<0.01). The acid content of the
      milk fat of the experimental group had a significantly higher content (p<0.05) of
      C18:0 and of C18:3omega6. LC-MS/MS analysis showed the presence of 3,4-DHPEA
      (36.0 MUg/L) in the milk of the DSOP-fed buffaloes, while other phenols were not
      found. DSOP, in the quantity utilized, can be used in the feeding of the
      lactating buffalo; the dietetic-nutritional characteristics of the milk are
      improved due to a greater contribution of tocopherols, retinol and the presence
      of hydroxytyrosol. 

PMID- 25049876
TI  - Nutrient Digestibility and Metabolizable Energy Content of Mucuna pruriens Whole
      Pods Fed to Growing Pelibuey Lambs.
AB  - The nutrient digestibility, nitrogen balance and in vivo metabolizable energy
      supply of Mucuna pruriens whole pods fed to growing Pelibuey lambs was
      investigated. Eight Pelibuey sheep housed in metabolic crates were fed increasing
      levels of Mucuna pruriens pods: 0 (control), 100 (Mucuna100), 200 (Mucuna200) and
      300 (Mucuna300) g/kg dry matter. A quadratic (p<0.002) effect was observed for
      dry matter (DM), neutral detergent fibre (aNDF), nitrogen (N) and gross energy
      (GE) intakes with higher intakes in the Mucuna100 and Mucuna200 treatments.
      Increasing M. pruriens in the diets had no effect (p>0.05) on DM and GE apparent
      digestibility (p<0.05). A linear reduction in N digestibility and N retention was
      observed with increasing mucuna pod level. This effect was accompanied by a
      quadratic effect (p<0.05) on fecal-N and N-balance which were higher in the
      Mucuna100 and Mucuna200 treatments. Urine-N excretion, GE retention and dietary
      estimated nutrient supply (metabolizable protein and metabolizable energy) were
      not affected (p>0.05). DM, N and GE apparent digestibility coefficient of M.
      pruriens whole pods obtained through multiple regression equations were 0.692,
      0.457, 0.654 respectively. In vivo DE and ME content of mucuna whole pod were
      estimated in 11.0 and 9.7 MJ/kg DM. It was concluded that whole pods from M.
      pruriens did not affect nutrient utilization when included in an mixed diet up to
      200 g/kg DM. This is the first in vivo estimation of mucuna whole pod ME value
      for ruminants. 

PMID- 25049877
TI  - Intestinal development and function of broiler chickens on diets supplemented
      with clinoptilolite.
AB  - The purpose of this study was to evaluate the effect of natural clinoptilolite
      (NCLI) and modified clinoptilolite (MCLI) on broiler performance, gut morphology,
      intestinal length and weight, and gut digestive enzyme activity. A total of 240 d
      old male chicks were randomly assigned to 3 treatments, each of which comprised 8
      pens of 10 chicks per pen. Birds in the control group were fed the basal diet,
      while those in the experimental groups were fed diets supplemented with NCLI at
      2% (NCLI group), or MCLI at 2% (MCLI group), respectively, for 42 d. Compared
      with the control, supplementation with NCLI or MCLI had no significant (p>0.05)
      effects on productive parameters from d 1 to 42. Supplementation with NCLI or
      MCLI had no influence on the relative length and weight of small intestine at d 1
      to 21. But supplementation with NCLI or MCLI significantly reduced the relative
      weight of duodenum. Supplementation with MCLI and NCLI was associated with
      greater (p<0.05) villus height in the jejunal and ileal mucosa compared with
      those areas in the controls from d 1 to 42. However, supplementation with NCLI
      and MCLI had no significant (p>0.05) influence on the crypt depth in the jejunal
      and ileal mucosa compared with those in the controls. The addition of either NCLI
      or MCLI to the diet improved the activities of total protease, and amylase in the
      small intestinal contents. In conclusion, supplementation with NCLI or MCLI in
      diets improved intestinal morphology, increased the intestinal length and weigh
      and gut digestive enzyme activity. 

PMID- 25049878
TI  - Effect of Conjugated Linoleic Acid Feeding on the Growth Performance and Meat
      Fatty Acid Profiles in Broiler: Meta-analysis.
AB  - The effect of conjugated linoleic acid (CLA) feeding on growth performance and
      fatty acid profiles in thigh meat of broiler chicken was investigated using meta
      analysis with a total of 9 studies. Overall effects were calculated by
      standardized mean differences between treatment (CLA fed) and control using
      Hedges's adjusted g from fixed and random effect models. Meta-regression was
      conducted to evaluate the effect of CLA levels. Subgroups in the same study were
      designated according to used levels of CLA, CP levels or substituted oils in
      diets. The effects on final body weight, weight gain, feed intake and feed
      conversion ratio were investigated as growth parameters. Total saturated and
      unsaturated fatty acid concentrations and C16:0, C18:0, C18:2 and C18:3
      concentrations in thigh meat of broiler chicken were used as fatty acid profile
      parameters. The overall effect of CLA feeding on final weight was negative and it
      was only significant in fixed effect model (p<0.01). Significantly lower weight
      gain, feed intake and higher feed conversion ratio compared to control were found
      (p<0.05). CLA feeding on the overall increased total saturated fatty acid
      concentration in broilers compared to the control diet (p<0.01). Total
      unsaturated fatty acid concentration was significantly decreased by CLA feeding
      (p<0.01). As for individual fatty acid profiles, C16:0, C18:0 and C18:3 were
      increased and C18:2 was significantly decreased by CLA feeding (p<0.01). In
      conclusion, CLA was proved not to be beneficial for improving growth performance,
      whereas it might be supposed that CLA is effective modulating n-6/n-3 fatty acids
      ratio in thigh meat. However, the economical compensation of the loss from
      suppressed growth performance and increased saturated fatty acids with the
      benefit from enhanced n-6/n-3 ratio should be investigated in further studies in
      order to propose an appropriate use of dietary CLA in the broiler industry. 

PMID- 25049879
TI  - Effects of dietary lysine levels on apparent nutrient digestibility and serum
      amino Acid absorption mode in growing pigs.
AB  - Two experiments were conducted to determine the effects of different dietary
      lysine levels on the apparent nutrient digestibility, the serum amino acid (AA)
      concentration, and the biochemical parameters of the precaval and portal vein
      blood in growing pigs. In Experiment 1, 15 noncannulated pigs received diets with
      different lysine densities (0.65%, 0.95%, and 1.25% lysine) for 13 d. A total
      collection digestion test was performed, and blood samples were collected from
      the precaval vein at the end of the experiment. In Experiment 2, four cannulated
      pigs were fed the same diets of Experiment 1. The experiment used a self-control
      experimental design and was divided into three periods. On d 5 of each period, at
      0.5 h before feeding and hourly up to 8 h after feeding, single blood samples
      were collected from catheters placed in the portal vein. In Experiment 1, some
      serum AAs (including lysine), serum urinary nitrogen (SUN), and total protein
      (TP) concentrations were significantly affected by the dietary lysine levels
      (p<0.05). Moreover, the 0.65% lysine treatment showed a significant lower
      apparent digestibility of gross energy, dry matter, crude protein, and phosphorus
      than the other treatments (p<0.05). In Experiment 2, serum lysine, histidine,
      phenylalanine, threonine, valine, isoleucine (p = 0.0588), triglyceride, and SUN
      (p = 0.0572) concentrations were significantly affected by the dietary lysine
      levels (p<0.05). Additionally, almost all of the determined serum AA and total AA
      concentrations reached their lowest values at 0.5 h before feeding and their
      highest values at 2 h after feeding (p<0.05). These findings indicate that the
      greatest absorption of AA occurred at 2 h after feeding and that the dynamic
      profile of serum AA is affected by the dietary lysine levels. Moreover, when the
      dietary lysine content was 0.95%, the growing pigs achieved a better nutrient
      digestibility and serum metabolites levels. 

PMID- 25049880
TI  - Effects of dietary thiazolidinedione supplementation on growth performance,
      intramuscular fat and related genes mRNA abundance in the longissimus dorsi
      muscle of finishing pigs.
AB  - The objective of this study was to investigate the effect of dietary
      supplementation with thiazolidinedione (TZD) on growth performance and meat
      quality of finishing pigs. In Experiment 1, 80 castrated finishing pigs (Large
      White*Landrace, BW = 54.34 kg) were randomly assigned to 2 treatments with 5
      replicates of 8 pigs each. The experimental pigs in the 2 groups were
      respectively fed with a diet with or without a TZD supplementation (15 mg/kg). In
      Experiment 2, 80 castrated finishing pigs (Large White*Landrace, BW = 71.46 kg)
      were divided into 2 treatments as designed in Experiment 1, moreover, carcass
      evaluations were performed. The results from Experiment 1 showed that TZD
      supplementation could significantly decreased the average daily feed intake
      (ADFI) (p<0.05) during 0 to 28 d, without impairing the average daily gain (ADG)
      (p>0.05). In Experiment 2, the ADG was significantly increased by TZD
      supplementation during 14 to 28 d and 0 to 28 d (p<0.05) and the feed:gain ratio
      (F:G) was significantly decreased by TZD supplementation during 0 to 28 d
      (p<0.05). Compared with the control group, TZD group had significantly higher
      serum triglyceride (TG) concentration at 28h and serum high-density lipoprotein
      (HDL) levels at 14 d (p<0.05). Moreover, there was an apparent improvement in the
      marbling score (p<0.10) and intramuscular fat (IMF) content (p<0.10) of the
      longissimus dorsi muscle in pigs treated by TZD supplementation. Real-time RT-PCR
      analyses demonstrated that pigs of TZD group had higher mRNA abundance of
      PPARgamma coactivator 1 (PGC-1) (p<0.05) and fatty acid-binding protein 3 (FABP3)
      (p<0.05) than pigs of control group. Taken together, these results suggested that
      dietary TZD supplementation could improve growth performance and increase the IMF
      content of finishing pigs through regulating the serum parameters and genes mRNA
      abundance involved in fat metabolism. 

PMID- 25049881
TI  - Effects of Dietary Chromium Methionine on Growth Performance, Carcass
      Composition, Meat Colour and Expression of the Colour-related Gene Myoglobin of
      Growing-finishing Pigs.
AB  - To investigate the effect of dietary chromium (Cr) as Cr methionine (CrMet) on
      growth performance, carcass traits, pork quality, meat colour and expression of
      meat colour-related genes in growing-finishing pigs, 189 crossbred
      Duroc*(Landrace*Yorkshire) growing-finishing pigs (male, castrated, average
      initial BW 74.58+/-1.52 kg) were selected and randomly allocated into four
      groups. Dietary treatments per kg of feed were as follows: 0 (CT), 0.3 mg/kg
      (T1), 0.6 mg/kg (T2) and 0.9 mg/kg (T3) Cr (in the form of CrMet; as-fed basis),
      and each treatment was replicated five times with 8 to 10 pigs per replicate pen.
      During the 28 d of the experiment, both the ADG and the ADFI increased linearly
      (p<0.05) as the level of dietary Cr increased. The F/G ratio decreased linearly
      (p<0.05). As dietary Cr increased, loin muscle areas (linear, p = 0.013) and
      average backfat thickness (linear, p = 0.072) decreased. Shear force (linear, p =
      0.070) and Commission Internationale de I'Eclairage (CIE) redness (quadratic, p =
      0.028) were increased. In addition, CIE Lightness (quadratic, p = 0.053) were
      decreased as dietary Cr increased. As dietary Cr increased, total myglobin (Mb)
      content (quadratic, p = 0.015) and the mb mRNA levels (quadratic, p = 0.046) in
      longissimus muscles of pigs were up-regulated. In conclusion, supplementation of
      dietary Cr improved growth and meat colour, but increased shear force and
      decreased IMF reduced palatability of longissimus muscles. Moreover, the
      increasing total Mb content and mb mRNA levels indicated that CrMet dietary
      supplementation may improve meat colour via up-regulating expression of the mb
      gene. 

PMID- 25049882
TI  - Automatic Detection of Cow's Oestrus in Audio Surveillance System.
AB  - Early detection of anomalies is an important issue in the management of group
      housed livestock. In particular, failure to detect oestrus in a timely and
      accurate way can become a limiting factor in achieving efficient reproductive
      performance. Although a rich variety of methods has been introduced for the
      detection of oestrus, a more accurate and practical method is still required. In
      this paper, we propose an efficient data mining solution for the detection of
      oestrus, using the sound data of Korean native cows (Bos taurus coreanea). In
      this method, we extracted the mel frequency cepstrum coefficients from sound data
      with a feature dimension reduction, and use the support vector data description
      as an early anomaly detector. Our experimental results show that this method can
      be used to detect oestrus both economically (even a cheap microphone) and
      accurately (over 94% accuracy), either as a standalone solution or to complement
      known methods. 

PMID- 25049883
TI  - Comparison of quality traits of meat from korean native chickens and broilers
      used in two different traditional korean cuisines.
AB  - With the aim of investigating the differences in the quality traits between
      Korean native chicken (Hanhyup, KNC) and broilers commonly used in two different
      traditional Korean cuisines, the chemical composition and sensory properties of
      breast and thigh meat from the two chicken strains were assessed. KNC for baeksuk
      (chicken meat braised in soup with various Oriental medicinal plants; KNL), KNC
      for samgyetang (similar to baeksuk but young chickens and ginseng are used; KNS),
      broiler for baeksuk (BL), and broiler for samgyetang (BS) were used as treatments
      in this study. KNL and KNS contained higher protein but lower fat content than BL
      and BS. The L* values of breast and thigh meat, but not the a* values, were
      significantly different between KNS and BS, whereas significant differences in
      both values were observed between KNL and BL. Compared to the other three types
      of chickens, KNS contained the highest total and insoluble collagen content, and
      KNL and BL showed higher inosine-5'-monophosphate content in their meat. Overall,
      KNL and KNS contributed darker, less tender meat with higher protein and less fat
      content together with more n-3 fatty acids, as opposed to their counterparts used
      for the same cuisines. Based on the results of the sensory analysis, even though
      there are some differences in physiochemical traits, different chicken sources do
      not differ in overall sensory quality. This information can help consumers to
      understand better the meat available for their preferred traditional cuisines. 

PMID- 25049884
TI  - Comparison of live performance and meat quality parameter of cross bred (korean
      native black pig and landrace) pigs with different coat colors.
AB  - Five hundred and forty crossbred (Korean native black pig*Landrace) F2 were
      selected at a commercial pig farm and then divided into six different coat color
      groups: (A: Black, B: White, C: Red, D: White spot in black, E: Black spot in
      white, F: Black spot in red). Birth weight, 21st d weight, 140th d weight and
      carcass weight varied among the different coat color groups. D group (white spot
      in black coat) showed a significantly higher body weight at each weigh (birth
      weight, 140th d weight and carcass weight) than did the other groups, whereas the
      C group (red coat color) showed a significantly lower body weight at finishing
      stage (140th d weight and carcass weight) compared to other groups. Meat quality
      characteristics, shear force, cooking loss and meat color were not significantly
      different among the different coat color groups, whereas drip loss was
      significantly higher in F than in other groups. Most blood characteristics were
      not significantly different among the different groups, except for the red blood
      cells. 

PMID- 25049885
TI  - Molecular Characterization and Expression Analysis of S6K1 in Cashmere Goats
      (Capra hircus).
AB  - p70 ribosomal S6 kinase (p70S6K) can integrate nutrient and growth factor signals
      to promote cell growth and survival. We report our molecular characterization of
      the complementary DNA (cDNA) that encodes the goat p70S6K gene 40S ribosomal S6
      kinase 1 (S6K1) (GenBank accession GU144017) and its 3' noncoding sequence in
      Inner Mongolia Cashmere goats (Capra hircus). Goat S6K1 cDNA was 2,272 bp and
      include an open reading frame (ORF) of 1,578 bp, corresponding to a polypeptide
      of 525 amino acids, and a 694-residue 3' noncoding sequence with a
      polyadenylation signal at nucleotides 2,218 to 2,223. The relative abundance of
      S6K1 mRNA was measured by real-time PCR in 6 tissues, and p70S6K expression was
      examined by immunohistochemistry in heart and testis. The phosphorylation of
      p70S6K is regulated by mitogen-activated protein kinase (MAPK) signaling in fetal
      fibroblasts. 

PMID- 25049886
TI  - Swine Leukocyte Antigen-DQA Gene Variation and Its Association with Piglet
      Diarrhea in Large White, Landrace and Duroc.
AB  - The swine leukocyte antigen class II molecules are possibly associated with the
      induction of protective immunity. The study described here was to investigate the
      relationship between polymorphisms in exon 2 of the swine DQA gene and piglet
      diarrhea. This study was carried out on 425 suckling piglets from three purebred
      pig strains (Large White, Landrace and Duroc). The genetic diversity of exon 2 in
      swine DQA was detected by PCR-SSCP and sequencing analysis, eight unique SSCP
      patterns (AB, BB, BC, CC, CD, BD, BE and DD) representing five specific allele (A
      to E) sequences were detected. Sequence analysis revealed 21 nucleotide variable
      sites and resulting in 12 amino acid substitutions in the populations. A moderate
      level polymorphism and significant deviations from Hardy-Weinberg equilibrium of
      the genotypes distribution were observed in the populations (p<0.01). The
      association analysis indicated that there was a statistically significant
      difference in the score of piglet diarrhea between different genotypes,
      individuals with genotype CC showed a lower diarrhea score than genotypes AB
      (0.98+/-0.09), BB (0.85+/-0.77) and BC (1.25+/-0.23) (p<0.05), and significantly
      low than genotype BE (1.19+/-0.19) (p<0.01), CC genotype may be a most resistance
      genotype for piglet diarrhea. 

PMID- 25049887
TI  - Single Nucleotide Polymorphisms of NLRP12 Gene and Association with Non-specific
      Digestive Disorder in Rabbit.
AB  - The NLRP12 (NLR family, pyrin domain containing 12) serves as a suppressor factor
      in the inflammatory response and protects the host against inflammation-induced
      damage. In the present study, we aimed to study the polymorphisms of NLRP12 gene
      and its association with susceptibility to non-specific digestive disorder (NSDD)
      in rabbits. We re-sequenced the entire coding region of the rabbit NLRP12 gene
      and detected a total of 19 SNPs containing 14 synonymous and five non-synonymous
      variations. Among them, the coding SNP (c.1682A>G), which would carry a potential
      functional implication, was subsequently subjected to genotyping for case-control
      association study (272 cases and 267 controls). The results revealed that allele
      A was significantly protective against NSDD with an odds ratio value of 0.884
      (95% confidence interval, 0.788 to 0.993; p = 0.038). We also experimentally
      induced NSDD in growing rabbits by feeding a fibre-deficient diet and
      subsequently investigated NLRP12 mRNA expression. The mRNA expression of NLRP12
      in healthy status was significantly higher than that in severe NSDD (p = 0.0016).
      The highest expression was observed in individuals carrying the protective
      genotype AA (p = 0.0108). These results suggested that NLRP12 was significantly
      associated with the NSDD in rabbits. However, the precise molecular mechanism of
      NLRP12 involving in the development of rabbit NSDD requires further research. 

PMID- 25049888
TI  - Kisspeptin-10 enhanced egg production in quails associated with the increase of
      triglyceride synthesis in liver.
AB  - Our previous results showed that kisspeptin-10 (Kp-10) injections via
      intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying
      rate in quails. In order to investigate the mechanism behind the effects of Kp-10
      on enhancing the egg laying rate in birds, this study focused on the alternations
      of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of
      age) were allocated to three groups randomly, and subjected to 0 (control, Con),
      10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p.
      once daily for three weeks, respectively. At d 52, quails were sacrificed and
      sampled for further analyses. Serum E2 concentration was increased by Kp-10
      injections, and reached statistical significance in H group. Serum triglyceride
      (TG) concentrations were increased by 46.7% in L group and 36.8% in H group,
      respectively, but did not reach statistical significance, and TG contents in
      liver were significantly elevated by Kp-10 injections in a dose-dependent manner.
      Serum total cholesterol (Tch) concentrations significantly decreased in H group,
      while in H group the hepatic Tch content was markedly increased. The level of non
      esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not
      altered by Kp-10 injections. The genes expression of sterol regulatory element
      binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II
      (apoVLDL-II), cholesterol 7alpha-hydroxylase (CYP7A1) and vitellogenin II (VTG
      II) were significantly up-regulated by high but not low dosage of Kp-10 injection
      compared to the control group. However, the expression of SREBP-2, acetyl-CoA
      carboxylase (ACCalpha), malic enzyme (ME), stearoyl-CoA (Delta9) desaturase 1
      (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3
      hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor
      alpha, beta (ERalpha and beta) mRNA were not affected by Kp-10 treatment. In line
      with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly
      higher in H group. Although the mRNA expression was not altered, the content of
      ERalpha protein in liver was also significantly increased in H group. However,
      SREBP-2 protein content in liver was not changed by Kp-10 treatment. In
      conclusion, exogenous Kp-10 consecutive injections during juvenile stage
      significantly advanced the tempo of egg laying in quails, which was associated
      with the significant elevation in hepatic lipids synthesis and transport. 

PMID- 25049889
TI  - Effect of Varying the Energy Density of Protein-adequate Diets on Nutrient
      Metabolism, Clinical Chemistry, Immune Response and Growth of Muzaffarnagari
      Lambs.
AB  - Effects of varied dietary energy densities on immune response and performance of
      Muzzafarnagari lambs were ascertained in a 180-d study. Animals (n = 24), in
      three groups, were fed diets providing 100% (100E), 80% (80E) or 70% (70E) of
      their metabolizable energy requirement. Mean nutrient digestibilities varied
      significantly among treatments. Nitrogen intake was lower (p<0.01) in the 70E.
      Nitrogen retention, was reduced (p<0.001) in 80E and 70E vs 100E. The average
      daily gain (p<0.001) was 47.01+/-4.23, 13.54+/-1.72 and -16.67+/-8.24 g for 100E,
      80E and 70E, respectively. Hemoglobin concentration, haematocrit, total and
      differential leukocyte counts were lower (p<0.001) for 80E and 70E than for 100E
      with a similar trend (p<0.05) for serum glucose and total protein. Serum cortisol
      was reduced (p<0.001) with decreased energy availability. Antibody titre to
      Brucella abortus S19 showed an initial reduction in 80E and 70E vs 100E. Delayed
      type hypersensitivity response was lower (p<0.001) in 80E and 70E vs 100E,
      accompanying a lower (p<0.001) nitric oxide production by the peripheral
      lymphocytes. It is concluded that the reduced dietary energy density
      significantly affects the growth performance and immune response of lambs. 

PMID- 25049890
TI  - In vitro Fermentation, Digestion Kinetics and Methane Production of Oilseed Press
      Cakes from Biodiesel Production.
AB  - Following the extraction of oil for biodiesel production, oilseed press cakes are
      high in fat. As the dietary supplementation of fat is currently considered the
      most promising strategy of consistently depressing methanogenesis, it follows
      that oilseed press cakes may have a similar potential for CH4 abatement. As such,
      this study aimed to characterise the nutritive value of several oilseed press
      cakes, glycerine and soybean meal (SBM) and to examine their effects on in vitro
      ruminal fermentation, digestion kinetics and CH4 production. Moringa press oil
      seeds exhibited the greatest in sacco effective degradability (ED) of DM and CP
      (p<0.05). In vitro gas production (ml/g digested DM) was not affected (p = 0.70)
      by supplement at 48 h of incubation. In vitro DMD was increased with the
      supplementation of glycerine and SBM at all levels of inclusion. Moringa oilseed
      press cakes produced the lowest CH4 (mg/g digested DM) at 6 and 12 h of
      incubation (p<0.05). The findings suggest that moringa oilseed press cake at 400
      g/kg DM has the greatest potential of the oilseed press cakes examined in this
      study, to reduce CH4 production, without adversely affecting nutrient
      degradability. 

PMID- 25049891
TI  - Milk production, milk composition, live weight change and milk Fatty Acid
      composition in lactating dairy cows in response to whole linseed supplementation.
AB  - The objective of this study was to determine the effects of whole linseed
      supplementation on performances and milk fatty acid composition of dairy cows.
      Thirty six Holstein Friesian crossbred lactating dairy cows were blocked by
      milking days first and then stratified random balanced for milk yields and body
      weight into three groups of 12 cows each. The control group received 300 g of
      palm oil. The second group was supplemented with 344 g/d of top-dressed whole
      linseed plus 150 g of palm oil and the third group was supplemented with 688 g/d
      of top-dressed whole linseed. All cows also received ad libitum grass silage
      (Brachiaria ruziziensis), had free access to clean water and were individually
      housed in a free-stall unit and individually fed according to treatments.
      Residual feeds were collected on 2 consecutive days weekly and at the end of the
      experiment. Feed samples were pooled to make representative samples for proximate
      and detergent analyses. Daily milk yields were recorded. Milk samples were
      collected on 2 consecutive days weekly. Live weights were recorded at the start
      and at the end of the experiment. Milk samples were taken on d 56 of the
      experiment and subjected to milk fatty acid composition. The results showed no
      statistical significant differences in intakes, live weight change, milk yields
      and milk compositions, however, C18:1, C18:3 and unsaturated FAs were increased
      while saturated FAs were reduced by whole linseed supplementation. It is
      recommended that the addition of 300 g/d oil from whole linseed could be
      beneficial to lactating dairy cows in early lactation. 

PMID- 25049892
TI  - Comparison of mathematical models applied to f1 dairy sheep lactations in organic
      farm and environmental factors affecting lactation curve parameter.
AB  - THE OBJECTIVE OF THIS STUDY WAS TO COMPARE THE GOODNESS OF FIT OF FOUR LACTATION
      CURVE MODELS: Wood's Gamma model (WD), Wilmink (WL), and Pollott's multiplicative
      two (POL2) and three parameters (POL3) and to determine the environmental factors
      affecting the complete lactation curve of F1 dairy sheep under organic
      management. A total of 5,382 weekly milk yields records from 150 ewes, under
      organic management were used. Residual mean square (RMS), determination
      coefficients (R(2)), and correlation (r) analysis were used as an indicator of
      goodness of fit for each model. WL model best fitted the lactation curves as
      indicated by the lower RMS values (0.019), followed by WD (0.023), POL2 (0.025)
      and POL3 (0.029). The four models provided total milk yield (TMY) estimations
      that were highly correlated (0.93 to 0.97) with observed TMY (89.9 kg). The four
      models under estimated peak yield (PY), whereas POL2 and POL3 gave nearer peak
      time lactation estimations. Ewes lambing in autumn had higher TMY and showed a
      typical curve shape. Higher TMY were recorded in second and third lambing. Season
      of lambing, number of lambing and type of lambing had a great influenced over TMY
      shaping the complete lactation curve of F1 dairy sheep. In general terms WL model
      showed the best fit to the F1 dairy sheep lactation curve under organic
      management. 

PMID- 25049893
TI  - Effects of plant herb combination supplementation on rumen fermentation and
      nutrient digestibility in beef cattle.
AB  - Four rumen-fistulated crossbred beef cattle (Brahman native) were randomly
      assigned according to a 4*4 Latin square design experiment to be fed plant herb
      supplements in their concentrate mixture. The treatments were: without herb
      supplementation (Control), lemongrass meal supplementation at 100 g/d (L),
      lemongrass meal supplementation at 100 g/d plus peppermint powder at 10 g/d (LP),
      and lemongrass meal supplementation at 100 g/d plus peppermint powder at 10 g/d
      with garlic powder 40 g/d (LPG), respectively. Based on the present study, the
      DMI and apparent digestibility of DM, OM, aNDF and ADF were not affected by
      dietary herb supplementation while CP digestibility tended to be decreased by
      herb supplement. Moreover, NH3-N and BUN were decreased in all herb supplemented
      treatments and there was a tendency to an increase in ruminal pH in all herb
      supplemented groups. While there was no change in TVFA and C4 among lemongrass
      treatments, C2 was decreased in all herb supplemented treatments while C3 was
      increased. Methane production by calculation was the lowest in the LP and LPG
      groups. Population sizes of bacteria and protozoa were decreased in all herb
      supplemented groups, but not fungal zoospores. In all supplemented groups, total
      viable and proteolytic bacteria were decreased, while amylolytic and cellulolytic
      bacteria were similar. More importantly, in all herb supplemented groups, there
      were higher N balances, while there was no difference among treatments on purine
      derivative (PD) excretion or microbial N. Based on the results above, it could be
      concluded that there was no negative effect on ruminal fermentation
      characteristics and nutrient utilization by plant herb supplement, but protozoal
      population and CH4 production were reduced. Thus, lemongrass alone or in
      combination with peppermint and garlic powder could be used as feed additives to
      improve rumen fermentation efficiency. 

PMID- 25049894
TI  - Effect of Saccharomyces cerevisiae Fermentation Product on Lactation Performance
      and Lipopolysaccharide Concentration of Dairy Cows.
AB  - To evaluate lactation performance and changes in plasma and fecal
      lipopolysaccharide (LPS) concentrations in response to the supplementation of
      Saccharomyces cerevisiae fermentation product (SC), two dairy farms were
      selected. On each farm, 32 cows in early to mid lactation (21 to 140 DIM) were
      blocked by parity and days in milk (DIM), and randomly assigned to one of the two
      treatments within block (Control or 56 g SC/cow/d). Effect of SC on lactation
      performance (daily) and changes in blood and fecal LPS level were examined on d 0
      and 28 of supplementation. The results showed that SC supplementation increased
      lactation performance of dairy cows on both farms. On Farm 1, milk production,
      3.5% fat corrected milk (FCM), and yield of milk fat and protein were greater
      (p<0.01) for cows supplemented with SC. Supplementation of SC increased
      percentage milk fat (p = 0.029) from 81 to 110 DIM. There was no significant
      effect (p>0.05) of SC supplementation on percentage of milk protein, dry matter
      intake and feed efficiency. On Farm 2, cows supplemented with SC had a greater
      (p<0.05) milk yield, percentage of milk fat and milk protein, yield of milk fat
      and protein, 3.5% FCM and feed efficiency. Supplemental SC had no effect on LPS
      concentrations in feces (p>0.05) while it trended to reduce (p = 0.07 or 0.207)
      the concentration in plasma. The results indicate that supplemental SC can
      increase lactation performance of dairy cattle and has potential for reducing
      plasma LPS concentration. 

PMID- 25049895
TI  - Metagenome Analysis of Protein Domain Collocation within Cellulase Genes of Goat
      Rumen Microbes.
AB  - In this study, protein domains with cellulase activity in goat rumen microbes
      were investigated using metagenomic and bioinformatic analyses. After the
      complete genome of goat rumen microbes was obtained using a shotgun sequencing
      method, 217,892,109 pair reads were filtered, including only those with 70%
      identity, 100-bp matches, and thresholds below E(-10) using METAIDBA. These
      filtered contigs were assembled and annotated using blastN against the NCBI
      nucleotide database. As a result, a microbial community structure with 1431
      species was analyzed, among which Prevotella ruminicola 23 bacteria and
      Butyrivibrio proteoclasticus B316 were the dominant groups. In parallel, 201
      sequences related with cellulase activities (EC.3.2.1.4) were obtained through
      blast searches using the enzyme.dat file provided by the NCBI database. After
      translating the nucleotide sequence into a protein sequence using Interproscan,
      28 protein domains with cellulase activity were identified using the HMMER
      package with threshold E values below 10(-5). Cellulase activity protein domain
      profiling showed that the major protein domains such as lipase GDSL, cellulase,
      and Glyco hydro 10 were present in bacterial species with strong cellulase
      activities. Furthermore, correlation plots clearly displayed the strong positive
      correlation between some protein domain groups, which was indicative of microbial
      adaption in the goat rumen based on feeding habits. This is the first metagenomic
      analysis of cellulase activity protein domains using bioinformatics from the goat
      rumen. 

PMID- 25049896
TI  - Effects of Replacing Dry-rolled Corn with Increasing Levels of Corn Dried
      Distillers Grains with Solubles on Characteristics of Digestion, Microbial
      Protein Synthesis and Digestible Energy of Diet in Hair Lambs Fed High
      concentrate Diets.
AB  - Four male lambs (Katahdin; average live weight 25.9+/-2.9 kg) with "T" type
      cannulas in the rumen and proximal duodenum were used in a 4*4 Latin square
      experiment to evaluate the influence of supplemental dry distillers grain with
      solubles (DDGS) levels (0, 10, 20 and 30%, dry matter basis) in substitution for
      dry-rolled (DR) corn on characteristics of digestive function and digestible
      energy (DE) of diet. Treatments did not influence ruminal pH. Substitution of DR
      corn with DDGS increased ruminal neutral detergent fiber (NDF) digestion
      (quadratic effect, p<0.01), but decreased ruminal organic matter (OM) digestion
      (linear effect, p<0.01). Replacing corn with DDGS increased (linear, p<=0.02)
      duodenal flow of lipids, NDF and feed N. But there were no treatment effects on
      flow to the small intestine of microbial nitrogen (MN) or microbial N efficiency.
      The estimated UIP value of DDGS was 44%. Postruminal digestion of OM, starch,
      lipids and nitrogen (N) were not affected by treatments. Total tract digestion of
      N increased (linear, p = 0.04) as the DDGS level increased, but DDGS substitution
      tended to decrease total tract digestion of OM (p = 0.06) and digestion of gross
      energy (p = 0.08). However, it did not affect the dietary digestible energy (DE,
      MJ/kg), reflecting the greater gross energy content of DDGS versus DR corn in the
      replacements. The comparative DE value of DDGS may be considered similar to the
      DE value of the DR corn it replaced up to 30% in the finishing diets fed to
      lambs. 

PMID- 25049897
TI  - Growth, Feed Utilization and Blood Metabolic Responses to Different Amylose
      amylopectin Ratio Fed Diets in Tilapia (Oreochromis niloticus).
AB  - A feeding trial was conducted in tilapia to determine the growth performance,
      nutrient digestibility, digestive enzymes, and postprandial blood metabolites in
      response to different dietary amylose-amylopectin ratios. Five isonitrogenous and
      isolipidic diets containing an equal starch level with different amylose
      amylopectin ratios of 0.11 (diet 1), 0.24 (diet 2), 0.47 (diet 3), 0.76 (diet 4)
      and 0.98 (diet 5) were formulated using high-amylose corn starch (as the amylose
      source) and waxy rice (as the amylopectin source). Each diet was hand-fed to six
      tanks of 15 fish each, three times a day over a 6-wk period. After the growth
      trial, a postprandial blood metabolic test was carried out. Fish fed diet 2
      exhibited the highest percent weight gain and feed efficiency and protein
      efficiency ratio, whereas fish fed with diet 5 showed the lowest growth and feed
      utilization among treatments. The digestibility for starch in fish fed diet 1 and
      2 was higher than those in fish fed with other diets (p<0.05). The highest
      activities for protease, lipase and amylase were found in fish fed the diet 2,
      diet 1, and diet 1 respectively among dietary treatments, while the lowest values
      for these indexes were observed in fish fed the diet 3, diet 5 and diet 4,
      respectively. The liver glycogen concentrations in fish fed diets 4 and 5 were
      found higher than in fish fed other diets (p<0.05). The feeding rate,
      hepatosomatic index, condition factor, and plasma parmeters (glucose,
      triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low
      density lipoprotein cholesterol) did not differ across treatments. In terms of
      postprandial blood responses, peak blood glucose and triglycerides were lower
      after 3 or 6 h in the fish fed with diets 3-5 than in the fish fed diet 1, but
      delayed peak blood total amino acid time was observed in fish fed with the diets
      1 or 2. The lowest peak values for each of the three blood metabolites were
      observed in fish fed diet 5. The results indicate that high-dietary amylose
      amylopectin ratio could compromise growth, but help in reducing the blood glucose
      stress on fish caused by postprandial starch load. 

PMID- 25049898
TI  - Estimation of the optimal ratio of standardized ileal digestible threonine to
      lysine for finishing barrows fed low crude protein diets.
AB  - Two experiments were conducted to determine the standardized ileal digestible
      (SID) lysine (Lys) requirement and the ideal SID threonine (Thr) to Lys ratio for
      finishing barrows. In Exp. 1, 120 barrows with an average body weight of 72.8+/
      3.6 kg were allotted to one of six dietary treatments in a randomized complete
      block design conducted for 35 d. Each diet was fed to five pens of pigs
      containing four barrows. A normal crude protein (CP) diet providing 15.3% CP and
      0.71% SID Lys and five low CP diets providing 12% CP with SID Lys concentrations
      of 0.51, 0.61, 0.71, 0.81 and 0.91% were formulated. Increasing the SID Lys
      content of the diet resulted in an increase in weight gain (linear effect p =
      0.04 and quadratic effect p = 0.08) and an improvement in feed conversion ratio
      (FCR) (linear effect p = 0.02 and quadratic effect p = 0.02). For weight gain and
      FCR, the estimated SID Lys requirement of finishing barrows were 0.71 and 0.71%
      (linear broken-line analysis), 0.79 and 0.78% (quadratic analysis), respectively.
      Exp. 2 was a 26 d dose-response study using SID Thr to Lys ratios of 0.56, 0.61,
      0.67, 0.72 and 0.77. A total of 138 barrows weighing 72.5+/-4.4 kg were randomly
      allotted to receive one of the five diets. All diets were formulated to contain
      0.61% SID Lys (10.5% CP), which is slightly lower than the pig's requirement.
      Weight gain was quadratically (p = 0.03) affected by SID Thr to Lys ratio while
      FCR was linearly improved (p = 0.02). The SID Thr to Lys ratios for maximal
      weight gain and minimal FCR and serum urea nitrogen (SUN) were 0.67, 0.71 and
      0.64 using a linear broken-line model and 0.68, 0.78 and 0.70 using a quadratic
      model, respectively. Based on the estimates obtained from the broken-line and
      quadratic analysis, we concluded that the dietary SID Lys requirement for both
      maximum weight gain and minimum FCR was 0.75%, and an optimum SID Thr to Lys
      ratio was 0.68 to maximize weight gain, 0.75 to optimize FCR and 0.67 to minimize
      SUN for finishing barrows. 

PMID- 25049899
TI  - The effects of enzyme complex on performance, intestinal health and nutrient
      digestibility of weaned pigs.
AB  - Two experiments were conducted to evaluate the effect of supplementing a corn
      soybean meal-based diet with an enzyme complex containing amylase, protease and
      xylanase on the performance, intestinal health, apparent ileal digestibility of
      amino acids and nutrient digestibility of weaned pigs. In Exp. 1, 108 piglets
      weaned at 28 d of age were fed one of three diets containing 0 (control), 100, or
      150 ppm enzyme complex for 4 wks, based on a two-phase feeding program namely 1
      to 7 d (phase 1) and 8 to 28 d (phase 2). At the end of the experiment, six pigs
      from the control group and the group supplemented with 150 ppm enzyme complex
      were chosen to collect digesta samples from intestine to measure viscosity and pH
      in the stomach, ileum, and cecum, as well as volatile fatty acid concentrations
      and composition of the microflora in the cecum and colon. There were linear
      increases (p<0.01) in weight gain, gain: feed ratio and digestibility of gross
      energy with the increasing dose rate of enzyme supplementation during the whole
      experiment. Supplementation with enzyme complex increased the digesta viscosity
      in the stomach (p<0.05) and significantly increased (p<0.01) the concentrations
      of acetic, propionic and butyric acid in the cecum and colon. Enzyme
      supplementation also significantly increased the population of Lactobacilli
      (p<0.01) in the cecum and decreased the population of E. coli (p<0.05) in the
      colon. In Exp. 2, six crossbred barrows (initial body weight: 18.26+/-1.21 kg),
      fitted with a simple T-cannula at the distal ileum, were assigned to three
      dietary treatments according to a replicated 3*3 Latin Square design. The
      experimental diets were the same as the diets used in phase 2 in Exp. 1. Apparent
      ileal digestibility of isoleucine (p<0.01), valine (p<0.05) and aspartic acid
      (p<0.05) linearly increased with the increasing dose rate of enzyme
      supplementation. In conclusion, supplementation of the diet with an enzyme
      complex containing amylase, protease and xylanase improved piglet performance.
      This is likely a result of improvement in nutrient digestibility, volatile fatty
      acid concentrations and bacteria ratio in the large intestine. 

PMID- 25049900
TI  - Zinc-chelated Vitamin C Stimulates Adipogenesis of 3T3-L1 Cells.
AB  - Adipose tissue development and function play a critical role in the regulation of
      energy balance, lipid metabolism, and the pathophysiology of metabolic syndromes.
      Although the effect of zinc ascorbate supplementation in diabetes or glycemic
      control is known in humans, the underlying mechanism is not well described. Here,
      we investigated the effect of a zinc-chelated vitamin C (ZnC) compound on the
      adipogenic differentiation of 3T3-L1 preadipocytes. Treatment with ZnC for 8 d
      significantly promoted adipogenesis, which was characterized by increased
      glycerol-3-phosphate dehydrogenase activity and intracellular lipid accumulation
      in 3T3-L1 cells. Meanwhile, ZnC induced a pronounced up-regulation of the
      expression of glucose transporter type 4 (GLUT4) and the adipocyte-specific gene
      adipocyte protein 2 (aP2). Analysis of mRNA and protein levels further showed
      that ZnC increased the sequential expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha),
      the key transcription factors of adipogenesis. These results indicate that ZnC
      could promote adipogenesis through PPARgamma and C/EBPalpha, which act
      synergistically for the expression of aP2 and GLUT4, leading to the generation of
      insulin-responsive adipocytes and can thereby be useful as a novel therapeutic
      agent for the management of diabetes and related metabolic disorders. 

PMID- 25049901
TI  - Properties of Milk Supplemented with Peanut Sprout Extract Microcapsules during
      Storage.
AB  - This study was carried out to investigate the physicochemical and sensory
      properties of milk with added powdered peanut sprout extract microcapsules
      (PPSEM) during the storage at 4 degrees C for 16 d. The size of PPSEM varies from
      3 to 10 MUm as observed by the scanning electron microscopy (SEM). The pH values
      of all samples ranged from 6.8 to 6.6 during the storage. Release of resveratrol
      for 0.5 and 1% PPSEM addition was about 0.89 MUl/ml and TBARS value found to
      lower during storage of 16 d. The a* and b* color values of high concentrations
      (1.5, 2.0, 2.5 and 3.0%) of PPSEM-added milk samples were significantly increased
      during the storage (p<0.05). The sensory test revealed that the overall
      acceptability of PPSEM (0.5 and 1%) added milk sample were quite similar to that
      of control. Based on the data, it was concluded that the low concentrations of
      the microcapsules (0.5 and 1.0%, w/v) could be suitable to produce the
      microcapsule-supplemented milk without significant adverse effects on the
      physicochemical and sensory properties of milk. 

PMID- 25049902
TI  - Feed energy evaluation for growing pigs.
AB  - Pigs require energy for maintenance and productive purposes, and an accurate
      amount of available energy in feeds should be provided according to their energy
      requirement. Available energy in feeds for pigs has been characterized as DE, ME,
      or NE by considering sequential energy losses during digestion and metabolism
      from GE in feeds. Among these energy values, the NE system has been recognized as
      providing energy values of ingredients and diets that most closely describes the
      available energy to animals because it takes the heat increment from digestive
      utilization and metabolism of feeds into account. However, NE values for diets
      and individual ingredients are moving targets, and therefore, none of the NE
      systems are able to accurately predict truly available energy in feeds. The DE or
      ME values for feeds are important for predicting NE values, but depend on the
      growth stage of pigs (i.e., BW) due to the different abilities of nutrient
      digestion, especially for dietary fiber. The NE values are also influenced by
      both environment that affects NE requirement for maintenance (NEm) and the growth
      stage of pigs that differs in nutrient utilization (i.e., protein vs. lipid
      synthesis) in the body. Therefore, the interaction among animals, environment,
      and feed characteristics should be taken into consideration for advancing feed
      energy evaluation. A more mechanistic approach has been adopted in Denmark as
      potential physiological energy (PPE) for feeds, which is based on the theoretical
      biochemical utilization of energy in feeds for pigs. The PPE values are,
      therefore, believed to be independent of animals and environment. This review
      provides an overview over current knowledge on energy utilization and energy
      evaluation systems in feeds for growing pigs. 

PMID- 25049903
TI  - Identification of Stearoyl-CoA Desaturase (SCD) Gene Interactions in Korean
      Native Cattle Based on the Multifactor-dimensionality Reduction Method.
AB  - Fat quality is determined by the composition of fatty acids. Genetic
      relationships between this composition and single nucleotide polymorphisms (SNPs)
      in the stearoyl-CoA desaturase1 (SCD1) gene were examined using 513 Korean native
      cattle. Single and epistatic effects of 7 SNP genetic variations were
      investigated, and the multifactor dimensionality reduction (MDR) method was used
      to investigate gene interactions in terms of oleic acid (C18:1), mono-unsaturated
      fatty acids (MUFAs) and marbling score (MS). The g.6850+77 A>G and g.14047 C>T
      SNP interactions were identified as the statistically optimal combination (C18:1,
      MUFAs and MS permutation p-values were 0.000, 0.000 and 0.001 respectively) of
      two-way gene interactions. The interaction effects of g.6850+77 A>G, g.10213 T>C
      and g.14047 C>T reflected the highest training-balanced accuracy (63.76%, 64.70%
      and 61.85% respectively) and was better than the individual effects for C18:1,
      MUFAs and MS. In addition, the superior genotype groups were AATTCC, AGTTCC,
      GGTCCC, AGTCCT, GGCCCT and AGCCTT. These results suggest that the selected SNP
      combination of the SCD1 gene and superior genotype groups can provide useful
      inferences for the improvement of the fatty acid composition in Korean native
      cattle. 

PMID- 25049905
TI  - Variance components and genetic parameters for milk production and lactation
      pattern in an ethiopian multibreed dairy cattle population.
AB  - The objective of this study was to estimate variance components and genetic
      parameters for lactation milk yield (LY), lactation length (LL), average milk
      yield per day (YD), initial milk yield (IY), peak milk yield (PY), days to peak
      (DP) and parameters (ln(a) and c) of the modified incomplete gamma function (MIG)
      in an Ethiopian multibreed dairy cattle population. The dataset was composed of
      5,507 lactation records collected from 1,639 cows in three locations (Bako, Debre
      Zeit and Holetta) in Ethiopia from 1977 to 2010. Parameters for MIG were obtained
      from regression analysis of monthly test-day milk data on days in milk. The cows
      were purebred (Bos indicus) Boran (B) and Horro (H) and their crosses with
      different fractions of Friesian (F), Jersey (J) and Simmental (S). There were 23
      breed groups (B, H, and their crossbreds with F, J, and S) in the population.
      Fixed and mixed models were used to analyse the data. The fixed model considered
      herd-year-season, parity and breed group as fixed effects, and residual as
      random. The single and two-traits mixed animal repeatability models, considered
      the fixed effects of herd-year-season and parity subclasses, breed as a function
      of cow H, F, J, and S breed fractions and general heterosis as a function of
      heterozygosity, and the random additive animal, permanent environment, and
      residual effects. For the analysis of LY, LL was added as a fixed covariate to
      all models. Variance components and genetic parameters were estimated using
      average information restricted maximum likelihood procedures. The results
      indicated that all traits were affected (p<0.001) by the considered fixed
      effects. High grade B*F cows (3/16B 13/16F) had the highest least squares means
      (LSM) for LY (2,490+/-178.9 kg), IY (10.5+/-0.8 kg), PY (12.7+/-0.9 kg), YD
      (7.6+/-0.55 kg) and LL (361.4+/-31.2 d), while B cows had the lowest LSM values
      for these traits. The LSM of LY, IY, YD, and PY tended to increase from the first
      to the fifth parity. Single-trait analyses yielded low heritability (0.03+/-0.03
      and 0.08+/-0.02) and repeatability (0.14+/-0.01 to 0.24+/-0.02) estimates for LL,
      DP and parameter c. Medium heritability (0.21+/-0.03 to 0.33+/-0.04) and
      repeatability (0.27+/-0.02 to 0.53+/-0.01) estimates were obtained for LY, IY,
      PY, YD and ln(a). Genetic correlations between LY, IY, PY, YD, ln(a), and LL
      ranged from 0.59 to 0.99. Spearman's rank correlations between sire estimated
      breeding values for LY, LL, IY, PY, YD, ln(a) and c were positive (0.67 to 0.99,
      p<0.001). These results suggested that selection for IY, PY, YD, or LY would
      genetically improve lactation milk yield in this Ethiopian dairy cattle
      population. 

PMID- 25049904
TI  - Genetic variation and phylogenetic relationships of Indian buffaloes of uttar
      pradesh.
AB  - India possesses a total buffalo population of 105 million out of which 26.1%
      inhabit Uttar Pradesh. The buffalo of Uttar Pradesh are described as nondescript
      or local buffaloes. Currently, there is no report about the genetic diversity,
      phylogenetic relationship and matrilineal genetic structure of these buffaloes.
      To determine the origin and genetic diversity of UP buffaloes, we sequenced and
      analysed the mitochondrial DNA D-loop sequences in 259 samples from entire Uttar
      Pradesh. One hundred nine haplotypes were identified in UP buffaloes that were
      defined by 96 polymorphic sites. We implemented neutrality tests to assess
      signatures of recent historical demographic events like Tajima's D test and Fu's
      Fs test. The phylogenetic studies revealed that there was no geographic
      differentiation and UP buffaloes had a single maternal lineage while buffaloes of
      Eastern UP were distinctive from rest of the UP buffaloes. 

PMID- 25049906
TI  - Effects of sheng hua tang on uterine involution and ovarian activity in
      postpartum dairy cows.
AB  - The effects of Sheng Hua Tang (SHT) on uterine involution and ovarian activity
      were investigated in postpartum dairy cows. SHT (70 g) was given to dairy cows (n
      = 10) to evaluate its effects for five days from the first postpartum day.
      Postpartum cows fed with a basal diet without SHT were used as the control group
      (n = 10). Ultrasounds and blood tests were recorded for four weeks from
      postpartum day seven with a 3-d interval. The results showed that the areas and
      diameters of endometria were significantly (p<0.01) reduced in the group that
      received SHT compared to the control group on the seventh postpartum day. The
      group that received SHT had an intrauterine fluid volume mean of 1.2+/-0.6 cm(3),
      which was significantly lower than that of the control group, 2.3+/-0.8 cm(3)
      (p<0.01) on the 13th postpartum day. In addition, the uterine tension score was a
      mean of 1.0+/-0.0 in the group that received SHT, which was also significantly
      lower than that of the control group, 1.5+/-0.5 (p<0.01) on the 19th postpartum
      day. Taken together, the Chinese herbal medicine remedy, SHT, promoted uterine
      involution and ovarian activity in postpartum dairy cows. 

PMID- 25049907
TI  - Analysis of ENPP2 in the Uterine Endometrium of Pigs Carrying Somatic Cell
      Nuclear Transfer Cloned Embryos.
AB  - Somatic cell nuclear transfer (SCNT) is a useful tool for animal cloning, but the
      efficiency of producing viable offspring by SCNT is very low. To improve this
      efficiency in the production of cloned pigs, it is critical to understand the
      interactions between uterine function and cloned embryos during implantation.
      Lysophosphatidic acid (LPA) is a lipid mediator that plays an important role in
      the establishment of pregnancy in pigs; however, LPA production in the uterine
      endometrium of pigs carrying SCNT-cloned conceptuses has not been determined.
      Therefore, we investigated expression of ENPP2, an LPA-generating enzyme, in the
      uterine endometrium of gilts with conceptuses derived from SCNT during the
      implantation period. Uterine endometrial tissue and uterine flushing were
      obtained from gilts carrying SCNT-derived conceptuses and from gilts carrying
      conceptuses resulting from natural mating on d 12 of pregnancy. Our results
      demonstrated no difference in the level of ENPP2 mRNA expression in the uterine
      endometrium between gilts carrying SCNT-derived conceptuses and gilts carrying
      naturally-conceived conceptuses, but secretion of ENPP2 protein into the uterine
      lumen did decrease significantly in pigs with SCNT-derived conceptuses. These
      results indicate that expression and secretion of ENPP2, which are critical for
      appropriate LPA production and successful pregnancy, are dysregulated in the
      uterine endometrium of pigs carrying SCNT-derived conceptuses. 

PMID- 25049908
TI  - Use of Awamori-pressed Lees and Tofu Lees as Feed Ingredients for Growing Male
      Goats.
AB  - Awamori is produced by fermenting steamed indica rice. Awamori-pressed lees is a
      by-product of the Awamori production process. Tofu lees is a by-product of the
      Tofu production process. Research was conducted to test if dried Awamori-pressed
      lees and Tofu lees can be used as a mixed feed ingredient for raising male goats.
      Eighteen male kids were divided into three groups of six animals (control feed
      group (CFG), Awamori-pressed lees mixed feed group (AMFG), Tofu lees mixed feed
      group (TMFG)). The CFG used feed containing 20% soybean meal as the main protein
      source, while the AMFG and TMFG used feed mixed with 20% dried Awamori-pressed
      lees or dried Tofu lees. The groups were fed mixed feed (volume to provide 100
      g/d increase in body weight) and alfalfa hay cubes (2.0 kg/d) twice a day (10:00,
      16:00). Klein grass hay and water was given ad libitum. Hay intake was measured
      at 10:00 and 16:00. Body weight and size measurements were taken once a month. At
      the end of the experiment, a blood sample was drawn from the jugular vein of each
      animal and the carcass characteristics, the physical and chemical characteristics
      of loin were analyzed. DCP and TDN intakes in AMFG and TMFG showed no significant
      difference to the CFG. Cumulative measurements of growth in body weight and size
      over the 10 mo period in the AMFG and TMFG were similar to the CFG. Blood
      parameter values were similar to those in normal goats. Dressing carcass weight
      and percentages, and total weight of meat in the AMFG were similar to that in the
      CFG, but smaller in the TMFG. The compressed meat juice ratio was higher in both
      the TMFG and AMFG than the CFG. While the fat in corn, Awamori-pressed lees, and
      Tofu lees contains more than 50% linoleic acid, the loin fat in both the AMFG and
      TMFG was very low in linoleic acid due to the increase in the content of oleic
      acid, stearic acid, and palmitic acid. This indicates that feeding on AMF and TMF
      does not inhibit hydrogenation by ruminal microorganisms. As in the CFG, the
      total essential and non-essential amino acids in the loin of the AMFG and TMFG
      were well balanced. Compared to the CFG, the AMFG and TMFG were high in taurine
      and carnosine. The results indicate dried Awamori-pressed lees and Tofu lees can
      be used as a feed ingredient for raising male goats. 

PMID- 25049909
TI  - Effects of Methylcellulose on Cellulolytic Bacteria Attachment and Rice Straw
      Degradation in the In vitro Rumen Fermentation.
AB  - An in vitro experiment was conducted to evaluate the effect of methylcellulose on
      the attachment of major cellulolytic bacteria on rice straw and its
      digestibility. Rice straw was incubated with ruminal mixture with or without 0.1%
      methylcellulose (MC). The attachment of F. succinogenes, R. flavefaciens and R.
      albus populations on rice straw was measured using real-time PCR with specific
      primer sets. Methylcellulose at the level of 0.1% decreased the attachment of all
      three major cellulolytic bacteria. In particular, MC treatment reduced (p<0.05)
      attachment of F. succinogenes on rice straw after 10 min of incubation while a
      significant reduction (p<0.05) in attachment was not observed until 4 h
      incubation in the case of R. flavefaciens and R. albus. This result indicated F.
      succinogenes responded to MC more sensitively and earlier than R. flavefaciens
      and R. albus. Dry matter digestibility of rice straw was subsequently inhibited
      by 0.1% MC, and there was a significant difference between control and MC
      treatment (p<0.05). Incubated cultures containing MC had higher pH and lower gas
      production than controls. Current data clearly indicated that the attachment of
      F. succinogenes, R. flavefaciens and R. albus on rice straw was inhibited by MC,
      which apparently reduced rice straw digestion. 

PMID- 25049910
TI  - Net Phosphorus Requirements of Dorper*Thin-tailed Han Crossbred Ram Lambs.
AB  - A comparative slaughter trial was conducted to estimate the phosphorus (P)
      requirement for maintenance and growth of crossbred lambs of Dorper with a
      Chinese indigenous sheep breed, thin-tailed Han sheep. Thirty-five Dorper*thin
      tailed Han crossbred, noncastrated ram lambs (20.3+/-0.22 kg of shrunk body
      weight (SBW)) were used. Seven lambs were randomly chosen and slaughtered at 20
      kg SBW as the baseline group for measuring initial body composition. Another
      seven lambs were also randomly chosen and offered a pelleted mixed diet for ad
      libitum intake and slaughtered at 28 kg SBW. The remaining 21 sheep were randomly
      divided into 3 groups with 7 sheep each and subject to the same diet of either 70
      or 40% of ad libitum intake. The 3 groups were slaughtered when the sheep fed ad
      libitum reached 35 kg of SBW. Body P contents were determined after slaughter.
      The results showed that the net P requirement for maintenance was 30.0 mg/kg of
      empty body weight (EBW) or 23.4 mg/kg body weight (BW), and the P requirement for
      growth decreased from 5.3 to 5.0 g/kg of EBW gain as the lamb grew from 20 to 35
      kg. The net P requirement for growth of Dorper*thin-tailed Han crossbred ram
      lambs was lower than that of sheep adopted by the American nutritional system. 

PMID- 25049911
TI  - Changes in microbial diversity, methanogenesis and fermentation characteristics
      in the rumen in response to medicinal plant extracts.
AB  - This study evaluated the in vitro effect of medicinal plant extracts on ruminal
      methanogenesis, four different groups of methanogens and ruminal fermentation
      characteristics. A fistulated Holstein cow was used as a donor of rumen fluid.
      Licorice and mugwort extracts (Glycyrrhiza uralensis and Artemisia capillaris,
      0.5% and 1% of total substrate DM, respectively), previously used as folk
      remedies, were added to an in vitro fermentation incubated with buffered-rumen
      fluid. Total gas production in Glycyrrhiza uralensis extract treatment was not
      significantly different between treatments (p<0.05) while total gas production in
      the Artemisia capillaris extract treatment was lower than that of the control.
      Artemisia capillaris extract and Glycyrrhiza uralensis extract reduced CH4
      emission by 14% (p<0.05) and 8% (p<0.05), respectively. Ciliate-associated
      methanogens population decreased by 18% in the medicinal plant extracts
      treatments. Medicinal plant extracts also affected the order Methanobacteriales
      community. Methanobacteriales diversity decreased by 35% in the Glycyrrhiza
      uralensis extract treatment and 30% in the Artemisia capillaris extract
      treatment. The order Methanomicrobiales population decreased by 50% in the 0.5%
      of Glycyrrhiza uralensis extract treatment. These findings demonstrate that
      medicinal plant extracts have the potential to inhibit in vitro ruminal
      methanogenesis. 

PMID- 25049912
TI  - Rumen fermentation and performance of lactating dairy cows affected by physical
      forms and urea treatment of rice straw.
AB  - The aim of this study was to determine the effect of different physical forms and
      urea treatment of rice straw on feed intake, rumen fermentation, and milk
      production. Four, multiparous Holstein crossbred dairy cows in mid-lactation with
      initial body weight (BW) of 409+/-20 kg were randomly assigned according to a 4*4
      Latin square design to receive four dietary treatments. The dietary treatments
      were as follows: untreated, long form rice straw (LRS), urea-treated (5%), long
      form rice straw (5% ULRS), urea-treated (2.5%), long form rice straw (2.5% ULRS)
      and urea-treated (2.5%), chopped (4 cm) rice straw (2.5% UCRS). Cows were fed
      with concentrate diets at a ratio of concentrate to milk yield of 1:2 and rice
      straw was fed ad libitum. The findings revealed significant improvements in total
      DM intake and digestibility by using long and short forms of urea-treated rice
      straw (p<0.05). Ruminal pH was not altered among all treatments (p>0.05), whereas
      ruminal NH3-N, BUN and MUN were found to be increased (p<0.01) by urea-treated
      rice straw as compared with untreated rice straw. Volatile fatty acids (VFAs)
      concentrations especially those of acetic acid were decreased (p<0.05) and those
      of propionic acid were increased (p<0.05), thus acetic acid:propionic acid was
      subsequently lowered (p<0.05) in cows fed with long or short forms of urea
      treated rice straw. The 2.5% ULRS and 2.5% UCRS had greater microbial protein
      synthesis and was greatest when cows were fed with 5% ULRS. The urea-treated rice
      straw fed groups had increased milk yield (p<0.05), while lower feed cost and
      greater economic return was in the 2.5% ULRS and 2.5% UCRS (p<0.01). From these
      results, it could be concluded that 2.5% ULRS could replace 5% ULRS used as a
      roughage source to maintain feed intake, rumen fermentation, efficiency of
      microbial protein synthesis, milk production and economical return in mid
      lactating dairy cows. 

PMID- 25049913
TI  - Effects of Ensiling Fermentation and Aerobic Deterioration on the Bacterial
      Community in Italian Ryegrass, Guinea Grass, and Whole-crop Maize Silages Stored
      at High Moisture Content.
AB  - The effects of storage period and aerobic deterioration on the bacterial
      community were examined in Italian ryegrass (IR), guinea grass (GG), and whole
      crop maize (WM) silages. Direct-cut forages were stored in a laboratory silo for
      3, 7, 14, 28, 56, and 120 d without any additives; live counts, content of
      fermentation products, and characteristics of the bacterial community were
      determined. 2,3-Butanediol, acetic acid, and lactic acid were the dominant
      fermentation products in the IR, GG, and WM silages, respectively. The acetic
      acid content increased as a result of prolonged ensiling, regardless of the type
      of silage crop, and the changes were distinctively visible from the beginning of
      GG ensiling. Pantoea agglomerans, Rahnella aquatilis, and Enterobacter sp. were
      the major bacteria in the IR silage, indicating that alcoholic fermentation may
      be due to the activity of enterobacteria. Staphylococcus sciuri and Bacillus
      pumilus were detected when IR silage was spoiled, whereas between aerobically
      stable and unstable silages, no differences were seen in the bacterial community
      at silo opening. Lactococcus lactis was a representative bacterium, although
      acetic acid was the major fermentation product in the GG silage. Lactobacillus
      plantarum, Lactobacillus brevis, and Morganella morganii were suggested to be
      associated with the increase in acetic acid due to prolonged storage.
      Enterobacter cloacae appeared when the GG silage was spoiled. In the WM silage,
      no distinctive changes due to prolonged ensiling were seen in the bacterial
      community. Throughout the ensiling, Weissella paramesenteroides, Weissella
      confusa, and Klebsiella pneumoniae were present in addition to L. plantarum, L.
      brevis, and L. lactis. Upon deterioration, Acetobacter pasteurianus, Klebsiella
      variicola, Enterobacter hormaechei, and Bacillus gibsonii were detected. These
      results demonstrate the diverse bacterial community that evolves during ensiling
      and aerobic spoilage of IR, GG, and WM silages. 

PMID- 25049914
TI  - Effects of Low Level Water-soluble Pentosans, Alkaline-extractable Pentosans, and
      Xylanase on the Growth and Development of Broiler Chicks.
AB  - This study investigated the effects of low levels of water-soluble pentosans
      (WSP), alkaline-extractable pentosans (AEP), and xylanase on the growth and organ
      development of broiler chicks. Three hundred and fifty 1-d-old female broiler
      chicks were randomly allocated into seven experimental groups of five pen
      replicates, with ten chicks per replicate. The control group consumed a corn
      soybean meal-based diet. Six dietary treatment groups consumed the basal diet
      supplemented with one of the following: WSP at 50 mg/kg (WSP50) or 100 mg/kg
      (WSP100); AEP at 50 mg/kg (AEP50) or 100 mg/kg (AEP100); or xylanase at 3 mg/kg
      (Xase3) or 6 mg/kg (Xase6). Data including the body weight, digestive organ
      weights, gut length, rectal digesta viscosity, and gut microflora and pH were
      collected on d 5, 10, and 15. When compared to the control group, WSP50 promoted
      body weight gain and organ growth throughout the study, calculated as 3-d
      averages (p<0.05). WSP100 increased weight gain and enhanced organ development
      (proventriculus, gizzard, and gut) on d 10 (p<0.05), but the 3-d averages were
      not different from the control group except for the weight of gizzard. Both Xase3
      and Xase6 increased the 3-d average weight gain and the growth of the gizzard
      (p<0.05). WSP50 increased the digesta viscosity compared to Xase3 on d 10 and 15
      (p<0.05). WSP50, Xase3, and Xase6 increased the concentration of Lactobacillus in
      the rectum when compared to the control group (p<0.05), but only Xase3 lowered
      the digesta pH in the ileum and cecum on d 10 and 15. AEP had minimal influence
      on the growth and organ development of broilers. The results showed that low
      levels of WSP, AEP, and xylanase had different effects and underlying mechanisms
      on the growth and organ development of broiler chicks. WSP50 could increase the
      growth performance of broilers fed a corn-soybean meal-based diet. 

PMID- 25049915
TI  - Effects of single cell protein replacing fish meal in diet on growth performance,
      nutrient digestibility and intestinal morphology in weaned pigs.
AB  - Three experiments were conducted to evaluate the ME value, standardized ileal
      digestibility (SID) of amino acids (AA) of fish meal, and the effects of single
      cell protein (Prosin and Protide) replacing fish meal in diet on growth
      performance, nutrient digestibility and intestinal morphology in weaned piglets.
      In Exp. 1, twenty-four barrows with initial BW of 30.8+/-2.6 kg were allotted to
      one of four dietary treatments. Diet 1 contained corn as the only energy source.
      The other three diets replaced 20% of the corn in diet 1 with one of the three
      protein feeds (fish meal, Prosin and Protide), and the DE and ME contents were
      determined by difference. In Exp. 2, eight barrows (initial BW of 25.6+/-3.2 kg)
      were fitted with ileal T-cannulas and allotted to a replicated 4*4 Latin square
      design. Three cornstarch-based diets were formulated using each of the protein
      feeds as the sole source of AA. A nitrogen-free diet was also formulated to
      measure endogenous losses of AA. In Exp. 3, one hundred and eighty piglets
      (initial BW of 7.95+/-1.59 kg) weaned at 28+/-2 d were blocked by weight and
      assigned to one of five treatments for a 28-d growth performance study, each
      treatment was fed to six pens with six pigs (three barrows and three gilts) per
      pen. The five treatments consisted of the control group (CON), which was a corn
      soybean meal diet containing 5% fish meal, and the other four treatments, which
      replaced a set amount of fish meal with either Prosin (2.5% or 5%) or Protide
      (2.5% or 5%). The diets were formulated to provide same nutrient levels. The
      results showed that on a DM basis, both of the DE and ME contents were lower in
      Prosin and Protide than that of fish meal (p<0.05). The SID of CP and all
      essential AA were greater in fish meal than in Prosin and Protide (p<0.05). The
      pigs fed CON diet had greater weight gain and lower feed conversion rate (FCR)
      than pigs fed 5% Prosin and 5% Protide diets (p<0.05). The digestibility of CP
      was greater in pigs fed CON, 2.5% Prosin and 2.5% Protide diets than the pigs fed
      5% Prosin and 5% Protide diets (p<0.05). Villus height in jejunum and ileum, and
      villus height to crypt depth ratio in the jejunum were higher (p<0.05) in pigs
      fed CON, 2.5% Prosin and 2.5% Protide diets compared with the 5% Prosin and 5%
      Protide diets. Pigs fed CON diet had greater villus height to crypt depth ratio
      in the ileum than the pigs fed 5% Prosin and 5% Protide diets (p<0.05). In
      conclusion, although Prosin and Protide contained lower ME content and SID of AA
      than fish meal, Prosin and Protide replacing 50% of fish meal in diet with
      identical nutrient levels could obtain similar performance, nutrient
      digestibility and intestinal morphology in weaned pigs. 

PMID- 25049916
TI  - The Relationship between Farmers' Perceptions and Animal Welfare Standards in
      Sheep Farms.
AB  - In this study, we investigated the relationship between welfare standards in
      sheep farms and farmers' perceptions of factors affecting animal welfare. We
      developed a scale of 34 items to measure farmers' perceptions of animal welfare.
      We examined the relationships among variables in farmers' characteristics, our
      observations, and farmers' expressed perceptions through a t test, variance
      analysis and correlation analysis. Results of the research suggested that higher
      welfare standards for sheep exist on farms run by farmers who have a higher
      perception level of animal welfare. These farmers believed that personnel and
      shelter conditions were more effective than veterinary inspection, feeding and
      other factors in terms of animal welfare. In addition, we detected a significant
      relationship between the farmers' perceptions and their gender, educational
      level, whether they enjoyed their work, or whether they applied the custom of
      religious sacrifice. Our results showed that emotional and cognitive factors
      related to farmers' perceptions may offer opportunities for progress in the
      domain of animal welfare. 

PMID- 25049917
TI  - Efficacy of tomato powder as antioxidant in cooked pork patties.
AB  - This study was carried out to determine the effects of tomato powder (TP) on
      cooked pork patties during storage at 10+/-1 degrees C in the dark. The total
      phenolic and flavonoid contents of TP extract were 26.22 mg gallic acid/100 g and
      3.52 mg quercetin/100 g, respectively. The extract of TP showed a potential
      antioxidant activity in the DPPH radical-scavenging assay (EC50 = 16.76 MUg/mL).
      Pork patties were manufactured with 0.25% (T1), 0.5% (T2), 0.75% (T3) and 1.0%
      (T4) TP in a basic formula (C). The pH and volatile basic nitrogen (VBN) values
      of T2, T3 and T4 patties were lower (p<0.05) than the C patties during storage.
      Increased concentration of TP in meat patties decreased (p<0.05) the 2
      thiobarbituric acid reactive substances (TBARS) and total plate count (TPC)
      values at d 7 of storage. Tomato treated-patties had lower (p<0.05) values for
      lightness (L*), but higher (p<0.05) values for redness (a*) and yellowness (b*)
      at d 3 and 7 of storage compared with the C. In the case of sensory evaluation,
      the scores of colour, flavour and overall acceptability of T3 and T4 patties were
      higher (p<0.05) than those of the C patty after 3 or 7 days of storage. 

PMID- 25049918
TI  - Perspective of membrane technology in dairy industry: a review.
AB  - Membrane technology has revolutionized the dairy sector. Different types of
      membranes are used in the industry for various purposes like extending the shelf
      life of milk without exposure to heat treatment, standardization of the major
      components of milk for tailoring new products as well increasing yield and
      quality of the dairy products, and concentrating, fractionation and purification
      of milk components especially valuable milk proteins in their natural state. In
      the cheese industry, membranes increase the yield and quality of cheese and
      control the whey volume, by concentrating the cheese milk. With the advancement
      of newer technology in membrane processes, it is possible to recover growth
      factor from whey. With the introduction of superior quality membranes as well as
      newer technology, the major limitation of membranes, fouling or blockage has been
      overcome to a greater extent. 

PMID- 25049919
TI  - - invited review - calcium digestibility and metabolism in pigs.
AB  - Calcium (Ca) and phosphorus (P) are minerals that have important physiological
      functions in the body. For formulation of diets for pigs, it is necessary to
      consider an appropriate Ca:P ratio for an adequate absorption and utilization of
      both minerals. Although both minerals are important, much more research has been
      conducted on P digestibility than on Ca digestibility. Therefore, this review
      focuses on aspects that are important for the digestibility of Ca. Only values
      for apparent total tract digestibility (ATTD) of Ca have been reported in pigs,
      whereas values for both ATTD and standardized total tract digestibility (STTD) of
      P in feed ingredients have been reported. To be able to determine STTD values for
      Ca it is necessary to determine basal endogenous losses of Ca. Although most Ca
      is absorbed in the small intestine, there are indications that Ca may also be
      absorbed in the colon under some circumstances, but more research to verify the
      extent of Ca absorption in different parts of the intestinal tract is needed.
      Most P in plant ingredients is usually bound to phytate. Therefore, plant
      ingredients have low digestibility of P due to a lack of phytase secretion by
      pigs. During the last 2 decades, inclusion of microbial phytase in swine diets
      has improved P digestibility. However, it has been reported that a high inclusion
      of Ca reduces the efficacy of microbial phytase. It is possible that formation of
      insoluble calcium-phytate complexes, or Ca-P complexes, not only may affect the
      efficacy of phytase, but also the digestibility of P and Ca. Therefore, Ca, P,
      phytate, and phytase interactions are aspects that need to be considered in Ca
      digestibility studies. 

PMID- 25049920
TI  - Differential Expression of PPARgamma, FASN, and ACADM Genes in Various Adipose
      Tissues and Longissimus dorsi Muscle from Yanbian Yellow Cattle and Yan Yellow
      Cattle.
AB  - The objective of this study was to investigate the correlation between cattle
      breeds and deposit of adipose tissues in different positions and the gene
      expressions of peroxisome proliferator-activated receptor gamma (PPARgamma),
      fatty acid synthase (FASN), and Acyl-CoA dehydrogenase (ACADM), which are
      associated with lipid metabolism and are valuable for understanding the
      physiology in fat depot and meat quality. Yanbian yellow cattle and Yan yellow
      cattle reared under the same conditions display different fat proportions in the
      carcass. To understand this difference, the expression of PPARgamma, FASN, and
      ACADM in different adipose tissues and longissimus dorsi muscle (LD) in these two
      breeds were analyzed using the Real-time quantitative polymerase chain reaction
      method (qRT-PCR). The result showed that PPARgamma gene expression was
      significantly higher in adipose tissue than in LD in both breeds. PPARgamma
      expression was also higher in abdominal fat, in perirenal fat than in the
      subcutaneous fat (p<0.05) in Yanbian yellow cattle, and was significantly higher
      in subcutaneous fat in Yan yellow cattle than that in Yanbian yellow cattle. On
      the other hand, FASN mRNA expression levels in subcutaneous fat and abdominal fat
      in Yan yellow cattle were significantly higher than that in Yanbian yellow
      cattle. Interestingly, ACADM gene shows greater fold changes in LD than in
      adipose tissues in Yan yellow cattle. Furthermore, the expressions of these three
      genes in lung, colon, kidney, liver and heart of Yanbian yellow cattle and Yan
      yellow cattle were also investigated. The results showed that the highest
      expression levels of PPARgamma and FASN genes were detected in the lung in both
      breeds. The expression of ACADM gene in kidney and liver were higher than that in
      other organs in Yanbian yellow cattle, the comparison was not statistically
      significant in Yan yellow cattle. 

PMID- 25049921
TI  - Genetic Diversity of mtDNA D-loop Polymorphisms in Laotian Native Fowl
      Populations.
AB  - Here, we studied the genetic diversity of native fowls in Laos by analyzing a
      mitochondrial DNA (mtDNA) sequence polymorphism. A 546-bp fragment of the mtDNA D
      loop region was sequenced in 129 chickens from the areas of Vientiane, Luang
      Prabang and Pakse. In total, 29 haplotypes were identified and formed five
      clades. Haplotype diversity and nucleotide diversity of the native fowls in Laos
      were 0.85536+/-0.0172 and 0.010158+/-0.005555, respectively. Although the Laotian
      native fowls were distributed across five clades, most of them were clustered in
      two main clades (A and B), which were originated in China. The other haplotypes
      were contained in clades D, F, and I, which originated from continental southeast
      Asia. These results suggest that multiple maternal lineages were involved in the
      origin of domestic chicken in Laos. Moreover, there appear to be at least two
      maternal lineages, one from China and the other from the southeast Asian
      continent. 

PMID- 25049922
TI  - Ingestive behavior and nitrogen balance of confined santa ines lambs fed diets
      containing soybean hulls.
AB  - The objective of this study was to assess the effect of substituting corn with
      soybean hulls on the ingestive behavior and nitrogen balance of Santa Ines lambs.
      A total of 25 lambs with an initial body weight of 20+/-2 kg at approximately six
      months of age, sheltered individually in stalls (1.10 m*1.0 m), considering an
      entirely casual experimental delineation. Soybean hulls were substituted for corn
      at 0, 250, 500, 750, and 1,000 g/kg of dry matter (DM). The time spent feeding,
      ruminating, masticating, and resting was not affected by the substitution of corn
      with soybean hulls. In fact, the feeding efficiency in g DM/h and the rumination
      efficiency in g DM/bolus increased linearly with soybean hull substitution in the
      feed. Although the nitrogen balance was not altered by the use of soybean hulls
      as a substitute for corn in the diets of Santa Ines lambs, the N ingested and N
      digested expressed in g/d, N retained as a percentage of that ingested, and N
      retained as a percentage of that digested displayed quadratic behavior. In
      conclusion, corn can be substituted with soybean hulls up to 1,000 g/kg of dry
      matter in the concentrate, without changing the ingestive behavior and nitrogen
      balance. 

PMID- 25049923
TI  - Maintenance Crude Protein Requirement of Penned Female Korean Spotted Deer
      (Cervus nippon).
AB  - This study was conducted to evaluate the protein requirement for maintenance of 2
      year-old female Korean spotted deer. In the course of the experiment, each of
      three hand-reared female spotted deer was fed three diets that were iso
      calorically formulated to contain low (approximately 7%), medium (12%), and high
      (17%) levels of crude protein (CP). Each of six trials included a 5-day
      transition, a 10-day preliminary, and a 7-day collection period. Dietary protein
      levels affected the apparent digestibility of CP (p<0.05) but not the apparent
      digestibility of dry matter, organic matter, or acid detergent fiber. All of the
      deer showed a positive CP balance on all of the diets. The maintenance CP
      requirement estimated by regression analysis was 4.17 g/kg metabolic body weight
      (W(0.75)).d. The maintenance digestible CP requirement was 1.42 g/kg W(0.75).d.
      The metabolic fecal CP was 1.95 g/kg W(0.75).d. The blood urea nitrogen of
      spotted deer increased (p<0.05) as the dietary protein levels increased. 

PMID- 25049924
TI  - Influence of Yeast Fermented Cassava Chip Protein (YEFECAP) and Roughage to
      Concentrate Ratio on Ruminal Fermentation and Microorganisms Using In vitro Gas
      Production Technique.
AB  - The objective of this study was to determine the effects of protein sources and
      roughage (R) to concentrate (C) ratio on in vitro fermentation parameters using a
      gas production technique. The experimental design was a 2*5 factorial arrangement
      in a completely randomized design (CRD). Factor A was 2 levels of protein sources
      yeast fermented cassava chip protein (YEFECAP) and soybean meal (SBM) and factor
      B was 5 levels of roughage to concentrate (R:C) ratio at 80:20, 60:40, 40:60,
      20:80, and 0:100, respectively. Rice straw was used as a roughage source. It was
      found that gas production from the insoluble fraction (b) of YEFECAP supplemented
      group was significantly higher (p<0.05) than those in SBM supplemented group.
      Moreover, the intercept value (a), gas production from the insoluble fraction
      (b), gas production rate constants for the insoluble fraction (c), potential
      extent of gas production (a+b) and cumulative gas production at 96 h were
      influenced (p<0.01) by R:C ratio. In addition, protein source had no effect
      (p>0.05) on ether in vitro digestibility of dry matter (IVDMD) and organic
      (IVOMD) while R:C ratio affected the IVDMD and IVOMD (p<0.01). Moreover, YEFECAP
      supplanted group showed a significantly increased (p<0.05) total VFA and C3 while
      C2, C2:C3 and CH4 production were decreased when compared with SBM supplemented
      group. In addition, a decreasing R:C ratio had a significant effect (p<0.05) on
      increasing total VFA, C3 and NH3-N, but decreasing the C2, C2:C3 and CH4
      production (p<0.01). Furthermore, total bacteria, Fibrobacter succinogenes,
      Ruminococcus flavefaciens and Ruminococcus albus populations in YEFECAP
      supplemented group were significantly higher (p<0.05) than those in the SBM
      supplemented group while fungal zoospores, methanogens and protozoal population
      remained unchanged (p>0.05) as compared between the two sources of protein.
      Moreover, fungal zoospores and total bacteria population were significantly
      increased (p<0.01) while, F. succinogenes, R. flavefaciens, R. albus, methanogens
      and protozoal population were decreased (p<0.01) with decreasing R:C ratio. In
      conclusion, YEFECAP has a potential for use as a protein source for improving
      rumen fermentation efficiency in ruminants. 

PMID- 25049925
TI  - Effects of eucalyptus crude oils supplementation on rumen fermentation,
      microorganism and nutrient digestibility in swamp buffaloes.
AB  - This study was conducted to investigate the effects of eucalyptus (E.
      Camaldulensis) crude oils (EuO) supplementation on voluntary feed intake and
      rumen fermentation characteristics in swamp buffaloes. Four rumen fistulated
      swamp buffaloes, body weight (BW) of 420+/-15.0 kg, were randomly assigned
      according to a 2*2 factorial arrangement in a 4*4 Latin square design. The
      dietary treatments were untreated rice straw (RS) without EuO (T1) and with EuO
      (T2) supplementation, and 3% urea-treated rice straw (UTRS) without EuO (T3) and
      with EuO (T4) supplementation. The EuO was supplemented at 2 mL/h/d in respective
      treatment. Experimental animals were kept in individual pens and concentrate
      mixture was offered at 3 g/kg BW while roughage was fed ad libitum. Total dry
      matter and roughage intake, and apparent digestibilites of organic matter and
      neutral detergent fiber were improved (p<0.01) by UTRS. There was no effect of
      EuO supplementation on feed intake and nutrient digestibility. Ruminal pH and
      temperature were not (p>0.05) affected by either roughage sources or EuO
      supplementation. However, buffaloes fed UTRS had higher ruminal ammonia nitrogen
      and blood urea nitrogen as compared with RS. Total volatile fatty acid and
      butyrate proportion were similar among treatments, whereas acetate was decreased
      and propionate molar proportion was increased by EuO supplementation. Feeding
      UTRS resulted in lower acetate and higher propionate concentration compared to
      RS. Moreover, supplementation of EuO reduced methane production especially in
      UTRS treatment. Protozoa populations were reduced by EuO supplementation while
      fungi zoospores remained the same. Total, amylolytic and cellulolytic bacterial
      populations were increased (p<0.01) by UTRS; However, EuO supplementation did not
      affect viable bacteria. Nitrogen intake and in feces were found higher in
      buffaloes fed UTRS. A positive nitrogen balance (absorption and retention) was in
      buffaloes fed UTRS. Supplementation of EuO did not affect nitrogen utilization.
      Both allantoin excretion and absorption and microbial nitrogen supply were
      increased by UTRS whereas efficiency of microbial protein synthesis was similar
      in all treatments. Findings of present study suggested that EuO could be used as
      a feed additive to modify the rumen fermentation in reducing methane production
      both in RS and UTRS. Feeding UTRS could improve feed intake and efficiency of
      rumen fermentation in swamp buffaloes. However, more research is warranted to
      determine the effect of EuO supplementation in production animals. 

PMID- 25049926
TI  - Influence of protein and energy level in finishing diets for feedlot hair lambs:
      growth performance, dietary energetics and carcass characteristics.
AB  - Forty-eight Pelibuey*Katahdin male intact lambs (23.87+/-2.84 kg) were used in an
      84-d feeding trial, with six pens per treatment in a 2*2 factorial design
      arrangement. The aim of the study was to evaluate the interaction of two dietary
      energy levels (3.05 and 2.83 Mcal/kg ME) and two dietary protein levels (17.5%
      and 14.5%) on growth performance, dietary energetics and carcass traits. The
      dietary treatments used were: i) High protein-high energy (HP-HE); ii) High
      protein-low energy (HP-LE); iii) Low protein-high energy (LP-HE), and iv) Low
      protein-low energy (LP-LE). With a high-energy level, dry matter intake (DMI)
      values were 6.1% lower in the low-protein diets, while with low-energy, the DMI
      values did not differ between the dietary protein levels. Energy levels did not
      influence the final weight and average daily gain (ADG), but resulted in lower
      DMI values and higher gain efficiencies. No effects of protein level were
      detected on growth performance. The observed dietary net energy (NE) ratio and
      observed DMI were closer than expected in all treatments and were not affected by
      the different treatments. There was an interaction (p<0.03) between energy and
      protein level for kidney-pelvic and heart fat (KPH), KPH was higher in lambs fed
      high energy and high protein diet but not in high energy and low protein diet.
      The KPH was increased (20.2%, p = 0.01) in high-energy diets, while fat thickness
      was increased (21.7%, p = 0.02) in high-protein diets. Therefore, it is concluded
      that dietary energy levels play a more important role in feed efficiency than
      protein levels in finishing lambs with a high-energy diet (>2.80 Mcal/kg ME).
      Providing a level of protein above 14.5% does not improves growth-performance,
      dietary energetics or carcass dressing percentage. 

PMID- 25049928
TI  - Effects of dietary levels of glycine, threonine and protein on threonine
      efficiency and threonine dehydrogenase activity in hepatic mitochondria of
      chicks.
AB  - This study was carried out to evaluate the relationship between threonine (Thr)
      efficiency and Thr dehydrogenase (TDG) activity as an indicator of Thr oxidation
      on chicks fed with levels of diets (CP [17.5% and 21.5%] and Thr [3.8 and 4.7
      g/100 g CP]; glycine [Gly][0.64% and 0.98%] and true digestible Thr [dThr] [0.45%
      and 0.60%]). Calculation of the Thr efficiency was based on N-balance data and an
      exponential N-utilization model, and TDG activity was determined as accumulation
      of aminoacetone and Gly during incubation of hepatic mitochondria. This study
      found that in the liver of chicks who received a diet containing up to 0.79% Thr
      (4.7 g Thr/100 g of CP) in the 17.5% CP diet, no significant (p>0.05) effect on
      TDG activity was observed. However, significantly (p = 0.014) increased TDG
      activity was observed with a diet containing 21.5% CP (4.7 g Thr/100 g of CP) and
      the efficiency of Thr utilization showed a significant (p = 0.001) decrease,
      indicating the end of the Thr limiting range. No significant (p>0.05) effect on
      the total TDG activity and accumulation of Gly was observed with addition of Gly
      to a diet containing 0.45% dThr. In addition, addition of Gly to a diet
      containing 0.60% dThr also did not result in a change in accumulation of Gly. Due
      to an increase in accumulation of aminoacetone, an elevated effect on total TDG
      activity was also observed. No significant (p>0.05) reduction in the efficiency
      of Thr utilization was observed after addition of Gly at the level of 0.45% dThr.
      However, significantly (p<0.001) reduced efficiency of Thr utilization was
      observed after addition of Gly at the level of 0.60% dThr. Collectively, we found
      that TDG was stimulated not only by addition of Thr and protein to the diet, but
      also by addition of Gly, and efficiency of Thr utilization was favorably affected
      by addition of Gly at the level near to the optimal Thr concentration. In
      addition, no metabolic requirement of Gly through the TDG pathway was observed
      with almost the same accumulation of Gly and a slight increase in TDG activity by
      addition of Gly. Thus, our findings suggest that determination of TDG activity
      and parameter of efficiency of Thr utilization may be useful for evaluation of
      dietary Thr level. 

PMID- 25049927
TI  - Effects of Different Dietary Cadmium Levels on Growth and Tissue Cadmium Content
      in Juvenile Parrotfish, Oplegnathus fasciatus.
AB  - This feeding trial was carried out to evaluate the effects of different dietary
      cadmium levels on growth and tissue cadmium content in juvenile parrotfish,
      Oplegnathus fasciatus, using cadmium chloride (CdCl2) as the cadmium source.
      Fifteen fish averaging 5.5+/-0.06 g (mean+/-SD) were randomly distributed into
      each of twenty one rectangular fiber tanks of 30 L capacity. Each tank was then
      randomly assigned to one of three replicates of seven diets containing 0.30 (C0),
      21.0 (C21), 40.7 (C41), 83.5 (C83), 162 (C162), 1,387 (C1,387) and 2,743 (C2,743)
      mg cadmium/kg diet. At the end of sixteen weeks of feeding trial, weight gain
      (WG), specific growth rate (SGR) and feed efficiency (FE) of fish fed C21 were
      significantly higher than those of fish fed C83, C162, C1,387 and C2,743
      (p<0.05). Weight gain, SGR and FE of fish fed C0, C21 and C41 were significantly
      higher than those of fish fed C162, C1,387 and C2,743. Protein efficiency ratio
      of fish fed C0, C21 and C41 were significantly higher than those of fish fed
      C1,387 and C2,743. Average survival of fish fed C0, C21, C41 and C162 were
      significantly higher than that of fish fed C2,743. Tissue cadmium concentrations
      increased with cadmium content of diets. Cadmium accumulated the most in liver,
      followed by gill and then muscle. Muscle, gill and liver cadmium concentrations
      of fish fed C0, C21, C41 and C83 were significantly lower than those of fish fed
      C162, C1,387 and C2,743. Based on the ANOVA results of growth performance and
      tissue cadmium concentrations the safe dietary cadmium level could be lower than
      40.7 mg Cd/kg diet while the toxic level could be higher than 162 mg Cd/kg diet. 

PMID- 25049929
TI  - Effect of dietary phytase transgenic corn on physiological characteristics and
      the fate of recombinant plant DNA in laying hens.
AB  - The study aimed to evaluate the potential effects of feeding with phytase
      transgenic corn (PTC) on organ weight, serum biochemical parameters and nutrient
      digestibility, and to determine the fate of the transgenic DNA in laying hens. A
      total of 144 50-week-old laying hens were grouped randomly into 2 treatments,
      with 8 replicates per treatment and 9 hens per replicate. Each treatment group of
      hens was fed with diets containing 62.4% non-transgenic conventional corn (CC) or
      PTC for 16 weeks. The phytase activity for CC was 37 FTU/kg of DM, whereas the
      phytase activity for PTC was 8,980 FTU/kg of DM. We observed that feeding PTC to
      laying hens had no adverse effect on organ weight or serum biochemical parameters
      (p>0.05). A fragment of a poultry-specific ovalbumin gene (ov) was amplified from
      all tissues of hens showing that the DNA preparations were amenable to PCR
      amplification. Neither the corn-specific invertase gene (ivr) nor the transgenic
      phyA2 gene was detected in the breast muscle, leg muscle, ovary, oviduct and
      eggs. The digestibility data revealed no significant differences between the hens
      that received the CC- and PTC-based diets in the digestibility of DM, energy,
      nitrogen and calcium (p>0.05). Phosphorus digestibility of hens fed the PTC-based
      diet was greater than that of hens fed the CC-based diet (58.03% vs 47.42%,
      p<0.01). Based on these results, it was concluded that the PTC had no deleterious
      effects on the organ weight or serum biochemical parameters of the laying hens.
      No recombinant phyA2 gene was detected in muscle tissues and reproductive organs
      of laying hens. The novel plant phytase was efficacious in improving the
      phosphorus digestibility of laying hens. 

PMID- 25049930
TI  - Effects of dietary protein levels for gestating gilts on reproductive
      performance, blood metabolites and milk composition.
AB  - This experiment was conducted to evaluate the effects of dietary CP levels in
      gestation under equal lysine content on reproductive performance, blood
      metabolites and milk composition of gilts. A total of 25 gilts (F1,
      Yorkshire*Landrace) were allotted to 4 dietary treatments at breeding in a
      completely randomized design, and fed 1 of 4 experimental diets containing
      different CP levels (11%, 13%, 15%, or 17%) at 2.0 kg/d throughout the gestation.
      Body weight of gilts at 24 h postpartum tended to increase linearly (p = 0.09) as
      dietary CP level increased. In lactation, backfat thickness, ADFI, litter size
      and weaning to estrus interval (WEI) did not differ among dietary treatments.
      There were linear increases in litter and piglet weight at 21 d of lactation
      (p<0.05) and weight gain of litter (p<0.01) and piglet (p<0.05) throughout the
      lactation as dietary CP level increased. Plasma urea nitrogen levels of gilts in
      gestation and at 24 h postpartum were linearly elevated as dietary CP level
      increased (p<0.05). Free fatty acid (FFA) levels in plasma of gestating gilts
      increased as dietary CP level increased up to 15%, and then decreased with
      quadratic effects (15 d, p<0.01; 90 d, p<0.05), and a quadratic trend (70 d, p =
      0.06). There were no differences in plasma FFA, glucose levels and milk
      composition in lactation. These results indicate that increasing dietary CP level
      under equal lysine content in gestation increases BW of gilts and litter
      performance but does not affect litter size and milk composition. Feeding over
      13% CP diet for gestating gilts could be recommended to improve litter growth. 

PMID- 25049931
TI  - Comparison of single and blend acidifiers as alternative to antibiotics on growth
      performance, fecal microflora, and humoral immunity in weaned piglets.
AB  - The banning of the use of antibiotics as feed additive has accelerated
      investigations of alternative feed additives in animal production. This
      experiment investigated the effect of pure citric acid or acidifier blend
      supplementation as substitute for antibiotic growth promoters on growth
      performance, fecal microbial count, and humoral immunity in weaned piglets
      challenged with Salmonella enterica serover Typhimurium and Escherichia coli KCTC
      2571. A total of 60 newly weaned piglets (crossbred, 28-d-old; average 8 kg
      initial weight) were randomly assigned to four dietary treatments in a completely
      randomized design. Dietary treatments included NC (negative control; basal diet),
      PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.5% pure
      citric acid), and T2 (basal diet+0.4% acidifier blend). All piglets were orally
      challenged with 5 mL of culture fluid containing 2.3*10(8) cfu/mL of E. coli KCTC
      2571 and 5.9*10(8) cfu/mL of S. typhimurium at the beginning of the experiment.
      The PC group showed the highest ADG and ADFI, whereas gain:feed was improved in
      the PC and T1 group (p<0.05). All dietary treatments showed significant reduction
      in fecal counts of Salmonella and E. coli, compared to NC (p<0.05), with PC being
      better than T1 and T2. Significant elevation in fecal Lactobacillus spp. counts
      was shown by treatments with T1, T2, and PC, whereas Bacillus spp. counts were
      increased by treatment with T1 and T2 compared to NC and PC diet (p<0.05). Serum
      IgG concentration was increased by T1 diet (p<0.05), whereas IgM and IgA were not
      significantly affected by any of the dietary treatments (p>0.05). From these
      above results, it can be concluded that, as alternatives to antibiotics dietary
      acidification with pure citric acid or acidifiers blend did not fully ameliorate
      the negative effects of microbial challenges in respect of growth performance and
      microbial environment, however improved immunity suggested further research with
      different dose levels. 

PMID- 25049932
TI  - Goat meat does not cause increased blood pressure.
AB  - While there are persistent rumors that the consumption of goat meat dishes
      increases blood pressure, there is no scientific evidence to support this. Two
      experiments were conducted to clarify whether or not blood pressure increases in
      conjunction with the consumption of goat meat dishes. In experiment 1, 24
      Dahl/Iwai rats (15 weeks old, body weight 309.3+/-11.1 g) were evenly separated
      into 4 groups. The control group (CP) was fed a diet containing 20% chicken and
      0.3% salt on a dry matter basis. The goat meat group (GM) was fed a diet
      containing 20% goat meat and 0.3% salt. The goat meat/salt group (GS) was fed a
      diet containing 20% goat meant and 3% to 4% salt. The Okinawan mugwort (Artemisia
      Princeps Pampan)/salt group (GY) was fed a diet containing 20% goat meat, 3% to
      4% salt and 5% of freeze-dried mugwort powder. The experiment 1 ran for a period
      of 14 weeks during which time the blood pressure of the animals was recorded. The
      GS, and GY groups consumed significantly more water (p<0.01) than the CP and GM
      groups despite the fact that their diet consumption levels were similar. The body
      weight of animals in the CP, GM, and GS groups was similar while the animals in
      the GY group were significantly smaller (p<0.01). The blood pressure in the GM
      group was virtually the same as the CP group throughout the course of the
      experiment. In contrast, while the blood pressure of the animals in the GS and GY
      group from 15 to 19 weeks old was the same as the CP group, their blood pressures
      were significantly higher (p<0.01) after 20 weeks of age. The GY group tended to
      have lower blood pressure than the GS group. In experiment 2, in order to clarify
      whether or not the increase in blood pressure in the GS group and the GY group in
      experiment 1 was caused by an excessive intake of salt, the effects on blood
      pressure of a reduction of salt in diet were investigated. When amount of salt in
      the diet of the GS and GY group was reduced from 4% to 0.3%, the animal's blood
      pressure returned to normotensive. These results indicate that, as in the case of
      chicken consumption, prolonged consumption of goat meat does not cause increased
      blood pressure, rather the large amount of salt used in the preparation of goat
      meat dishes is responsible for the increase in blood pressure. 

PMID- 25049933
TI  - Effect of mechanically deboned chicken meat hydrolysates on the physicochemical
      properties of imitation fish paste.
AB  - This study investigated on the effects of adding mechanically deboned chicken
      meat (MDCM) hydrolysates on the quality properties of imitation fish paste (IFP)
      during storage. IFP was prepared from Alaska Pollack, spent laying hens surimi
      and protein hydrolysates which were enzymatically extracted from MDCM. The study
      was designed as a 3*4 factorial design with three MDCM hydrolysate content groups
      (0%, 0.4%, and 0.8%) and four storage times (0, 2, 4, and 6 weeks). Addition of
      MDCM hydrolysates increased crude fat content but lowered water content (p<0.05).
      The breaking force of IFP, an indicator of gel formation, increased in treated
      groups compared to control (p<0.05). Angiotensin I-converting enzyme (ACE)
      activity was inhibited and free radical scavenging activity increased with
      increasing MDCM hydrolysate content (p<0.05). In conclusion, the addition of MDCM
      to IFP improves gel characteristics. Additionally, protein hydrolysates from MDCM
      serve as a potential source of ACE inhibiting peptides. 

PMID- 25049934
TI  - Deletion of the lmna gene induces growth delay and serum biochemical changes in
      C57BL/6 mice.
AB  - The A-type lamin deficient mouse line (Lmna (-/-) ) has become one of the most
      frequently used models for providing insights into many different aspects of A
      type lamin function. To elucidate the function of Lmna in the growth and
      metabolism of mice, tissue growth and blood biochemistry were monitored in Lmna
      deficient mice, heterozygous (Lmna (+/-) ) and wide-type (Lmna (+) (/) (+) )
      backcrossed to C57BL/6 background. At 4 weeks after birth, the weight of various
      organs of the Lmna (-/-), Lmna (+/-) and Lmna (+) (/) (+) mice was measured. A
      panel of biochemical analyses consisting of 15 serological tests was examined.
      The results showed that Lmna deficient mice had significantly decreased body
      weight and increased the ratio of organ to body weight in most of tissues.
      Compared with Lmna (+) (/) (+) and Lmna (+/-) mice, Lmna (-/-) mice exhibited
      lower levels of ALP (alkaline phosphatase), Chol (cholesterol), CR (creatinine),
      GLU (glucose), HDL (high-density lipoprotein cholesterol) and higher levels of
      ALT (alanine aminotransferase) (p<0.05). Lmna (-/-) mice displayed higher AST
      (aspartate aminotransferase) values and lower LDL (lowdensity lipoprotein
      cholesterol), CK-MB (creatine kinase-MB) levels than Lmna (+) (/) (+) mice
      (p<0.05). There were no significant differences among the three groups of mice
      with respect to BUN (blood urea nitrogen), CK (creatine kinase), Cyc C (cystatin
      C), TP (total protein), TG (triacylglycerols) and UA (uric acid) levels (p>0.05).
      These changes of serological parameters may provide an experimental basis for the
      elucidation of Lmna gene functions. 

PMID- 25049935
TI  - Effect of dietary supplementation of procyanidin on growth performance and immune
      response in pigs.
AB  - This study was performed to determine the effect of dietary supplementation of
      procyanidin on growth performance, blood characteristics, and immune function in
      growing pigs. In experiment 1 (Exp. 1), thirty-two crossbred pigs with an initial
      BW of 19.2+/-0.3 kg were allocated into 4 treatments for an 8-wk experiment: i)
      CON (basal diet), ii) MOS 0.1 (basal diet+0.1% mannanoligosaccharide), iii) Pro-1
      (basal diet+0.01% procyanidin), and iv) Pro-2 (basal diet+0.02% procyanidin).
      Pigs fed Pro-1 and Pro-2 diets had greater (p<0.05) gain:feed ratio compared with
      those fed CON or MOS 0.1 diets. Serum creatinine concentration was less (p<0.05)
      in Pro-2 treatment than those in CON, MOS 0.1 and Pro-1 treatments. In Exp. 2,
      twelve pigs (BW 13.4+/-1.3 kg) received basal diet with i) 0 (CON), ii) 0.02%
      (Pro-0.02%), and iii) 0.04% procyanidin (Pro-0.04%) for 4 wk. Concentration of
      platelets was lower (p<0.05) in the Pro-0.04% group compared to CON at 24 h after
      lipopolysaccharide (LPS) challenge. In addition, secretion of cytokines from
      cultured peripheral blood mononuclear cells (PBMC) in the presence or absence of
      procyanidin was examined. The levels of interleukin (IL)-1beta, IL-6 and tumor
      necrosis factor (TNF)-alpha were lower (p<0.05) in Pro (LPS-stimulated
      PBMCs+procyanidin) than those in CON (LPS-stimulated PBMCs+PBS) at 4 h after LPS
      challenge. These data suggest that dietary addition of procyanidin improves feed
      efficiency and anti-inflammatory cytokines of pigs. 

PMID- 25049936
TI  - Effects of Housing Systems on Behaviour, Performance and Welfare of Fast-growing
      Broilers.
AB  - This experiment aimed to evaluate the effects of different housing systems on
      behavioral activities, welfare and meat quality of fast-growing broilers. Two
      hundred broilers were allocated into two housing systems: indoor housing vs
      indoor with outdoor access. Their general behavior (feeding, drinking, fighting,
      standing, lying, walking, investigating, dust-bathing and preening) was observed,
      and tonic immobility, fluctuating asymmetry of legs and wings were measured, and
      meat quality was analyzed. The results showed that the indoor-housed broilers
      with outdoor access had significant higher standing, walking, investigating, dust
      bathing and preening than those indoor only. However, farming system was not
      found to significantly affect their feeding, drinking and fighting activities
      (p>0.05). The value of FA of tibia length of the broilers with outdoor access was
      significantly lower than that of the indoor-housed birds (1.57+/-1.30 vs 2.76+/
      1.40, p<0.05), while no difference was found for the value of FA in tibia
      diameter and wing length (p>0.05). TI of the broilers with outdoor access was
      165.5 that was significantly higher than that (147.2) of the indoor birds
      (p<0.05). However, death rate in the outdoor run groups was significantly higher
      than that of the indoor ones (2.0+/-0.81 vs 4.0+/-0.82, p<0.05). Meat quality was
      not affected by the two farming systems. It can be concluded that the results of
      this study may suggest that the indoor housing with outdoor access provides
      enriched environment for broilers and facilitates the expression of natural
      behaviors of the broilers but resulted in poorer performance and higher death
      rate. 

PMID- 25049937
TI  - Modulation of the somatotropic axis in periparturient dairy cows.
AB  - This review focuses on modulation of growth hormone (GH) and its downstream
      actions on periparturient dairy cows undergoing physiological and metabolic
      adaptations. During the periparturient period, cows experience a negative energy
      balance implicating that the feed intake does not meet the total energy demand
      for the onset of lactation. To regulate this metabolic condition, key hormones of
      somatotropic axis such as GH, IGF-I and insulin must coordinate adaptations
      required for the preservation of metabolic homeostasis. The hepatic GHR1A
      transcript and GHR protein are reduced at parturition, but recovers on
      postpartum. However, plasma IGF-I concentration remains low even though hepatic
      abundance of the GHR and IGF-I mRNA return to pre-calving value. This might be
      caused by alternation in IGFBPs and ALS genes, which consequently affect the
      plasma IGF-I stability. Plasma insulin level declines in a parallel manner with
      the decrease in plasma IGF-I after parturition. Increased GH stimulates the
      lipolytic effects and hepatic glucose synthesis to meet the energy requirement
      for mammary lactose synthesis, suggesting that GH antagonizes insulin-dependent
      glucose uptake and attenuates insulin action to decrease gluconeogenesis. 

PMID- 25049938
TI  - Estimation of Genetic Parameters for Real-time Ultrasound Measurements for Hanwoo
      Cows at Different Ages and Pregnancy Status.
AB  - The purpose of this study was to estimate genetic parameters of ultrasound
      measurements for longissimus dorsi muscle area (LMA), backfat thickness (BFT),
      and marbling score (MS) in Hanwoo cows (N = 3,062) at the ages between 18 and 42
      months. Data were collected from 100 Hanwoo breeding farms in Gyeongbuk province,
      Korea, in 2007 and 2008. The cows were classified into four different age groups,
      i.e. 18 to 22 months (the first pregnancy period), 23 to 27 (the first
      parturition), 28 to 32 (the second pregnancy), and 33 to 42 (the second
      parturition), respectively. For each age group, a multi-trait animal model was
      used to estimate variance components and heritabilities of the three traits. The
      averages of LMA, BFT, and MS measurements across the cows of all age groups were
      50.1 cm(2), 4.62 mm, and 3.04, respectively and heritability estimates were 0.09,
      0.10, and 0.08 for the respective traits. However, when the data were analyzed in
      different age groups, heritability estimates of LMA and BFT were 0.24 and 0.47,
      respectively, for the cows of 18 to 22 months of age, and 0.21 for MS in the 28
      to 32 months old cows. When the cows of all age groups were used, the estimates
      of genetic (phenotypic) correlations were 0.43 (0.35), -0.06 (0.34) and 0.21
      (0.32) between LMA and BFT, LMA and MS, and BFT and MS, respectively. However, in
      the cow age group between 28 and 32 (18 and 22) months, the estimates of genetic
      (phenotypic) correlations were 0.05 (0.29), -0.15 (0.24) and 0.38 (0.24), for the
      respective pairs of traits. These results suggest that genetic, environmental,
      and phenotypic variations differ depending on cow age, such that care must be
      taken when ultrasound measurements are applied to selection of cows for meat
      quality. 

PMID- 25049939
TI  - Effect of Dietary Concentrate:forage Ratios and Undegraded Dietary Protein on
      Nitrogen Balance and Urinary Excretion of Purine Derivatives in Dorper*thin
      tailed Han Crossbred Lambs.
AB  - THIS STUDY AIMED TO INVESTIGATE DIETARY CONCENTRATE: forage ratios (C:F) and
      undegraded dietary protein (UDP) on nitrogen balance and urinary excretion of
      purine derivatives (PD) in lambs. Four Dorper*thin-tailed Han crossbred castrated
      lambs with 62.3+/-1.9 kg body weight at 10 months of age were randomly assigned
      to four dietary treatments in a 2*2 factorial arrangement of two levels of C:F
      (40:60 and 60:40) and two levels of UDP (35% and 50% of CP), according to a
      complete 4*4 Latin-square design. Each experimental period lasted for 19 d. After
      a 7-d adaptation period, lambs were moved into individual metabolism crates for
      12 d including 7 d of adaption and 5 d of metabolism trial. During the metabolism
      trial, total urine was collected for 24 h and spot urine samples were also
      collected at different times. Urinary PD was measured using a colorimetric method
      and creatinine was measured using an automated analyzer. Intake of dry matter
      (DM) (p<0.01) and organic matter (OM) (p<0.01) increased as the level of UDP
      decreased. Fecal N was not affected by dietary treatment (p>0.05) while urinary N
      increased as the level of UDP decreased (p<0.05), but decreased as dietary C:F
      increased (p<0.05). Nitrogen retention increased as dietary C:F increased
      (p<0.05). As dietary C:F increased, urinary excretion of PD increased (p<0.05),
      but was not affected by dietary UDP (p>0.05) or interaction between dietary
      treatments (p>0.05). Daily excretion of creatinine was not affected by dietary
      treatments (p<0.05), with an average value of 0.334+/-0.005 mmol/kg BW(0.75). A
      linear correlation was found between total PD excretion and PDC index (R(2) =
      0.93). Concentrations of creatinine and PDC index in spot urine were unaffected
      by sampling time (p>0.05) and a good correlation was found between the PDC index
      (average value of three times) of spot urine and daily excretion of PD (R(2) =
      0.88). These results suggest that for animals fed ad libitum, the PDC index in
      spot urine is effective to predict daily excretion of PD. In order to improve the
      accuracy of the spot sampling technique, an appropriate lag phase between the
      time of feeding and sampling should be determined so that the sampling time can
      coincide with the peak concentration of PD in the urine.

PMID- 25049940
TI  - Clitoria ternatea L. as a Potential High Quality Forage Legume.
AB  - Samples of Clitoria ternatea L. (Cunha) were harvested at 35, 50, 70, and 90 d
      after a uniformity harvest in a field study designed as a completely randomized
      design with a total of 18 experimental plots. The dry matter yield of the whole
      plant was separated quantitatively into leaves, stems, and pods at each
      harvesting age. Chemical analyses and in vitro gas production kinetics were
      performed to assess the quality of the plant parts. Yields, chemical composition,
      and estimates of gas production parameters were analyzed by fitting a mixed
      statistical model with two types of covariance structures as follows: variance
      components and an unrestricted structure with heterogeneous variances. Fast and
      slow gas yielding pools were detected for both leaves and stems, but only a
      single pool was detected for pods. The homoscedasticity assumption was more
      likely for all variables, except for some parameters of the gas production
      kinetics of leaves and stems. There was no presence of typical pods at 35 and 50
      d. In the leaves, the fibrous fractions were affected, whereas the non-fibrous
      fractions were unaffected by the harvesting age. The harvesting age affected the
      majority of the chemical constituents and gas kinetic parameters related to the
      stems. The leaves of this legume were the least affected part by the aging
      process. 

PMID- 25049941
TI  - Diversity of butyrivibrio group bacteria in the rumen of goats and its response
      to the supplementation of garlic oil.
AB  - This study aimed to investigate the diversity of the Butyrivibrio group bacteria
      in goat rumen and its response to garlic oil (GO) supplementation as revealed by
      molecular analysis of cloned 16S rRNA genes. Six wethers fitted with ruminal
      fistulas were assigned to two groups for a cross-over design with 28-d
      experimental period and 14-d interval. Goats were fed a basal diet without
      (control) or with GO ruminal infusion (0.8 g/d). Ruminal contents were used for
      DNA extraction collected before morning feeding on d 28. A total bacterial clone
      library was firstly constructed by nearly full-length 16S rRNA gene cloned
      sequences using universal primers. The resulting plasmids selected by
      Butyrivibrio-specific primers were used to construct a Butyrivibrio group
      specific bacterial clone library. Butyrivibrio group represented 12.98% and
      10.95% of total bacteria in control and GO group, respectively. In libraries,
      clones were classified to the genus Pseudobutyrivibrio, Butyrivibrio and others
      within the family Lachnospiraceae. Additionally, some specific clones were
      observed in GO group, being classified to the genus Ruminococcus and others
      within the family Ruminococcaceae. Based on the criterion that the similarity was
      97% or greater with database sequences, there were 29.73% and 18.42% of clones
      identified as known isolates (i.e. B. proteoclasticus and Ps. ruminis) in control
      and GO groups, respectively. Further clones identified as B. fibrisolvens (5.41%)
      and R. flavefaciens (7.89%) were specifically found in control and GO groups,
      respectively. The majority of clones resembled Ps. ruminis (98% to 99%
      similarity), except for Lachnospiraceae bacteria (87% to 92% similarity) in the
      two libraries. The two clone libraries also appeared different in Shannon
      diversity index (control 2.47 and GO group 2.91). Our results indicated that the
      Butyrivibrio group bacteria had a complex community with considerable unknown
      species in the goat rumen. 

PMID- 25049942
TI  - Effects of Combining Feed Grade Urea and a Slow-release Urea Product on
      Characteristics of Digestion, Microbial Protein Synthesis and Digestible Energy
      in Steers Fed Diets with Different Starch:ADF Ratios.
AB  - As a result of the cost of grains, the replacement of grains by co-products (i.e.
      DDGS) in feedlot diets is a common practice. This change produces diets that
      contain a lower amount of starch and greater amount of fibre. Hypothetically,
      combining feed grade urea (U) with slow release urea (Optigen) in this type of
      diet should elicit a better synchrony between starch (high-rate of digestion) and
      fibre (low-rate of digestion) promoting a better microbial protein synthesis and
      ruminal digestion with increasing the digestible energy of the diet. Four
      cannulated Holstein steers (213+/-4 kg) were used in a 4*4 Latin square design to
      examine the combination of Optigen and U in a finishing diet containing different
      starch:acid detergent fibre ratios (S:F) on the characteristics of digestive
      function. Three S:F ratios (3.0, 4.5, and 6.0) were tested using a combination of
      U (0.80%) and Optigen (1.0%). Additionally, a treatment of 4.5 S:F ratio with
      urea (0.80% in ration) as the sole source of non-protein nitrogen was used to
      compare the effect of urea combination at same S:F ratio. The S:F ratio of the
      diet was manipulated by replacing the corn grain by dried distillers grain with
      solubles and roughage. Urea combination did not affect ruminal pH. The S:F ratio
      did not affect ruminal pH at 0 and 2 h post-feeding but, at 4 and 6 h, the
      ruminal pH decreased as the S:F ratio increased (linear, p<0.05). Ruminal
      digestion of OM, starch and feed N were not affected by urea combination or S:F
      ratio. The urea combination did not affect ADF ruminal digestion. ADF ruminal
      digestion decreased linearly (p = 0.02) as the S:F ratio increased. Compared to
      the urea treatment (p<0.05) and within the urea combination treatment (quadratic,
      p<0.01), the flow of microbial nitrogen (MN) to the small intestine and ruminal
      microbial efficiency were greater for the urea combination at a S:F ratio of 4.5.
      Irrespective of the S:F ratio, the urea combination improved (2.8%, p = 0.02)
      postruminal N digestion. As S:F ratio increased, OM digestion increased, but ADF
      total tract digestion decreased. The combination of urea at 4.5 S:F improved (2%,
      p = 0.04) the digestible energy (DE) more than expected. Combining urea and
      Optigen resulted in positive effects on the MN flow and DE of the diet, but
      apparently these advantages are observed only when there is a certain proportion
      of starch:ADF in the diet. 

PMID- 25049943
TI  - Assessment of the nutritive value of whole corn stover and its morphological
      fractions.
AB  - This study investigated the chemical composition and ruminal degradability of
      corn stover in three maize-planting regions in Qiqihaer, Heilongjiang Province,
      China. The whole stover was separated into seven morphological fractions, i.e.,
      leaf blade, leaf sheath, stem rind, stem pith, stem node, ear husk, and corn
      tassel. The assessment of nutritive value of corn stover and its fractions was
      performed based on laboratory assays of the morphological proportions, chemical
      composition, and in situ degradability of dry matter (DM), neutral detergent
      fiber (NDF), and acid detergent fiber (ADF). The chemical composition of corn
      stover was significantly different from plant top to bottom (p<0.05). Among the
      whole corn stover and seven morphological fractions, leaf blade had the highest
      crude protein (CP) content and the lowest NDF and ADF contents (p<0.05), whereas
      stem rind had the lowest CP content and the highest ADF and acid detergent lignin
      (ADL) contents (p<0.05). Ear husk had significantly higher NDF content and
      relatively lower ADL content than other corn stover fractions. Overall, the
      effective degradability of DM, NDF, and ADF in rumen was the highest in leaf
      blade and stem pith, followed by ear husk. The results indicate that leaf blade,
      ear husk, and stem pith potentially have higher nutritive values than the other
      fractions of corn stover. This study provides reference data for high-efficiency
      use of corn stover in feeding ruminants. 

PMID- 25049944
TI  - Ensiling Characteristics and the In situ Nutrient Degradability of a By-product
      Feed-based Silage.
AB  - This study was conducted to evaluate the ensiling characteristics and the in situ
      degradability of a by-product feed (BF)-based silage. Before ensilation, the BF
      based mixture was composed of 50% spent mushroom substrate, 21% recycled poultry
      bedding, 15% ryegrass straw, 10.8% rice bran, 2% molasses, 0.6% bentonite, and
      0.6% microbial inoculant on a wet basis and ensiled for up to 4 weeks. The BF
      based silage contained on average 39.3% moisture, 13.4% crude protein (CP), and
      52.2% neutral detergent fiber (NDF), 49% total digestible nutrient, and 37.8%
      physically effective NDF1.18 on a dry matter (DM) basis. Ensiling the BF-based
      silage for up to 4 weeks affected (p<0.01) the chemical composition to a small
      extent, increased (p<0.05) the lactic acid and NH3-N content, and decreased
      (p<0.05) both the total bacterial and lactic acid bacterial counts from 10(9) to
      10(8) cfu/g when compared to that before ensiling. These parameters indicated
      that the silage was fermented and stored well during the 4-week ensiling period.
      Compared with rice or ryegrass straws, the BF-based silage had a higher (p<0.05)
      water-soluble and filterable fraction, a lower insoluble degradable DM and CP
      fraction (p<0.05), a lower digestible NDF (p<0.05) fraction, a higher (p<0.05) DM
      and CP disappearance and degradability rate, and a lower (p<0.05) NDF
      disappearance and degradability rate. These results indicated that cheap, good
      quality BF-based roughage could be produced by ensiling SMS, RPB, rice bran, and
      a minimal amount of straw. 

PMID- 25049945
TI  - The net energy values of corn, dried distillers grains with solubles and wheat
      bran for laying hens using indirect calorimetry method.
AB  - The present study was conducted to estimate the NE values of corn, dried
      distillers grains with solubles (DDGS) and wheat bran (WB) for laying hens based
      on an indirect calorimetry method and nitrogen balance measurements. A total of
      576 twenty-eight-wk-old Dwarf Pink-shell laying hens were randomly assigned to
      four groups fed a basal diet (BD) or a combination of BD with 50% corn or 20%
      DDGS or 20% WB, with four replicates each. After a 7-d adaptation period, each
      replicate with 36 hens were kept in one of the two respiration chambers to
      measure the heat production (HP) for 6 days during the feeding period and
      subsequent 3-d fasting. The equilibrium fasting HP (FHP) provided an estimate of
      NE requirements for maintenance (NEm). The NE values of test feedstuffs was
      estimated using the difference method. Results showed that the heat increment
      that contributed 35.34 to 37.85% of ME intake was not influenced by experimental
      diets (p>0.05) when expressed as Mcal/kg of DM feed intake. Lighting increased
      the HP in hens in an fed-state. The FHP decreased over time (p<0.05) with the
      lowest value determined on the third day of starvation. No significant difference
      between treatments was found on FHP of d 3 (p>0.05). The estimated AME, AMEn, and
      NE values were 3.46, 3.44 and 2.25 Mcal/kg DM for corn, 3.11, 2.79, and 1.80
      Mcal/kg DM for DDGS, 2.14, 2.10, and 1.14 Mcal/kg DM for WB, respectively. The
      net availability of AME of corn tended to be numerically higher than DDGS and WB
      (p = 0.096). In conclusion, compared with corn, the energy values of DDGS and WB
      were overestimated when expressed on an AME basis. 

PMID- 25049946
TI  - Effect of Sea Tangle (Laminaria japonica) and Charcoal Supplementation as
      Alternatives to Antibiotics on Growth Performance and Meat Quality of Ducks.
AB  - A total of 150 growing ducks were assigned to five dietary treatments to study
      the effect of sea tangle and charcoal (STC) supplementation on growth performance
      and meat characteristics in a completely randomized design. There were six
      replicates and five ducklings in each replication. The five dietary treatments
      were control, antibiotic, and 0.1%, 0.5%, and 1% STC supplemented diets. No
      significant differences were found on ADG, ADFI, and gain:feed among treatments
      in different weeks. The overall (0 to 3 weeks) ADFI decreased in antibiotic
      treatment (p<0.05) whereas the gain:feed increased significantly upon 1.0% STC
      supplementation compared to control (p<0.05). No significant variation was found
      in meat chemical composition except crude fat content which was high in 1.0% STC
      dietary group (p<0.05). Meat cholesterol was reduced in 0.1% STC group (p<0.05)
      compared to other dose levels while serum cholesterol was unaffected. High
      density lipoprotein (HDL) content was high in 1.0% STC (p<0.05) and low density
      lipoprotein (LDL) was low in 0.1% and 1.0% STC dietary groups (p = 0.06). No
      significant effect was found on the thiobarbituric acid reactive substances
      (TBARS) of fresh meat, whereas the TBARS value of meat preserved for 1 week was
      reduced significantly in STC dietary groups (p<0.05). The 0.1% STC dietary group
      showed an increased myristic acid (p = 0.07) content whereas, the content of
      eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids increased in STC
      supplementation than antibiotic group (p<0.05). An increased concentration of
      omega-3 fatty acids and a reduced ratio of n-6/n-3 PUFA ratio was found upon 1.0%
      STC supplementation compared to antibiotic dietary group (p<0.05). Therefore,
      1.0% STC dietary supplementation can be used as alternatives to antibiotics in
      duck production. 

PMID- 25049947
TI  - Dietary Supplementation of Benzoic Acid and Essential Oil Compounds Affects
      Buffering Capacity of the Feeds, Performance of Turkey Poults and Their
      Antioxidant Status, pH in the Digestive Tract, Intestinal Microbiota and
      Morphology.
AB  - Three trials were conducted to evaluate the effect of supplementation of a basal
      diet with benzoic acid or thymol or a mixture of essential oil blends (MEO) or a
      combination of benzoic acid with MEO (BMEO) on growth performance of turkey
      poults. Control groups were fed a basal diet. In trial 1, benzoic acid was
      supplied at levels of 300 and 1,000 mg/kg. In trial 2, thymol or the MEO were
      supplied at levels of 30 mg/kg. In trial 3, the combination of benzoic acid with
      MEO was evaluated. Benzoic acid, MEO and BMEO improved performance, increased
      lactic acid bacteria populations and decreased coliform bacteria in the caeca.
      Thymol, MEO and BMEO improved antioxidant status of turkeys. Benzoic acid and
      BMEO reduced the buffering capacity compared to control feed and the pH values of
      the caecal content. Benzoic acid and EOs may be suggested as an effective
      alternative to AGP in turkeys. 

PMID- 25049948
TI  - Effects of Adding Super Dose Phytase to the Phosphorus-deficient Diets of Young
      Pigs on Growth Performance, Bone Quality, Minerals and Amino Acids
      Digestibilities.
AB  - Two experiments were conducted to evaluate the efficacy of feeding an Escherichia
      coli (E. coli) derived phytase to pigs fed P deficient, corn-soybean meal diets.
      In Exp. 1, one hundred and twenty crossbred piglets (9.53+/-0.84 kg) were
      allocated to one of five treatments which consisted of four low P diets (0.61%
      Ca, 0.46% total P and 0.24% non-phytate P) supplemented with 0, 500, 1,000, or
      20,000 FTU/kg E. coli phytase as well as a positive control formulated to be
      adequate in all nutrients (0.77% Ca, 0.62% total P and 0.42% non-phytate P). The
      treatments were applied to six pens with four pigs per pen for 28 days. In Exp.
      2, ten crossbred pigs (19.66+/-1.16 kg) fitted with ileal T-cannula were used in
      a nutrient balance study. The pigs were assigned to treatments similar to those
      used in Exp. 1 in a doubly replicated 5*4 incomplete Latin square design (5 diets
      with 4 periods). Each period consisted of a 5-d adjustment period followed by a 3
      d total collection of feces and urine and then a 2-d collection of ileal digesta.
      Supplementation with phytase linearly increased (p<0.05) weight gain, feed
      intake, feed efficiency, bone breaking strength and fat-free dry and ash bone
      weight. There were linear increases (p<0.01) in the apparent ileal digestibility
      (AID) of DM, GE, CP, Ca, total P, inositol hexaphosphate (IP6) and some AA with
      increasing dose of E. coli phytase. Pigs fed 20,000 FTU/kg had a greater (p<0.05)
      AID of IP6 (80% vs 59% or 64%, respectively) than pigs fed diets with 500 or
      1,000 FTU/kg phytase. There were linear increases (p<0.05) in the total tract
      digestibility of Ca, total P, Na, K, Mg, and Zn as well as in the retention of Mg
      and Zn with increased phytase dose. The retention and utilization of Cu, and the
      total tract digestibility of CP and Cu quadratic increased (p<0.05) with
      increased phytase dose. In conclusion, supplementation of 500 FTU of phytase/kg
      and above effectively hydrolyzed phytate in low-P corn-soybean diets for pigs. In
      addition, a super dose of phytase (20,000 FTU/kg) hydrolyzed most of the IP6 and
      consequently further improved mineral use, protein utilization and performance. 

PMID- 25049949
TI  - Efficacy of flaxseed flour as bind enhancing agent on the quality of extended
      restructured mutton chops.
AB  - Consumers have become very conscious about their nutrition and well being due to
      changes in their socio-economic lifestyle and rapid urbanization. Therefore,
      development of technology for production of low cost and functional meat products
      is urgently required. One such approach is innovative restructuring technology in
      which binding of meat pieces still remains the main challenge and extension of
      product is generally associated with poor binding and texture. Thus, the present
      study was envisaged as an attempt to solve this problem by the incorporation of
      flaxseed flour (FF) as bind enhancing agent. The FF was used at three different
      levels viz., 0.5%, 1%, and 1.5% to replace lean meat in pre-standardized
      restructured mutton chops formulation. The products were subjected to analysis
      for physico-chemical, sensory and textural properties. Cooking yield, moisture
      percentage and fat percentage increased with increase in the level of
      incorporation of FF, however, protein percent and pH decreased with increase in
      the level of incorporation. Shear force value of product incorporated with 1.5%
      FF was significantly higher (p<0.01) than control and product containing 0.5% FF
      level. Among the sensory attributes, product with 1% flaxseed flour showed
      significantly higher values (p<0.05) for general appearance, binding, texture and
      overall acceptability. Hardness showed significant increasing (p<0.01) values
      with increasing levels of incorporation of flaxseed flour, however all other
      parameters of texture profile analysis showed a decreasing trend. On the basis of
      sensory scores and physico-chemical properties, the optimum incorporation level
      of FF was adjudged as 1%. Products incorporated with optimum level of flaxseed
      flour (1%) were also assessed for water activity and microbiological quality
      during the storage period of 15 days. It was found that the extended restructured
      product could be safely stored under refrigeration (4 degrees C+/-1 degrees C) in
      low density polyethylene (LDPE) pouches for 15 days without marked deterioration
      in sensory and microbiological quality. Thus, it was concluded that flaxseed
      flour can be used as a good bind enhancing agent in extended restructured meat
      products at an economic cost. 

PMID- 25049950
TI  - Combined effects of high pressure processing and addition of soy sauce and olive
      oil on safety and quality characteristics of chicken breast meat.
AB  - This study was conducted to evaluate the combined effect of high pressure (HP)
      with the addition of soy sauce and/or olive oil on the quality and safety of
      chicken breast meats. Samples were cut into 100 g pieces and 10% (w/w) of soy
      sauce (SS), 10% (w/w) of olive oil (OO), and a mixture of both 5% of soy sauce
      and 5% olive oil (w/w) (SO) were pressurized into meat with high pressure at 300
      or 600 MPa. Cooking loss was lower in OO samples than SS samples. With increased
      pressure to 600 MPa, the oleic acid content of OO samples increased. The total
      unsaturated fatty acids were the highest in SO and OO 600 MPa samples. Lipid
      oxidation was retarded by addition of olive oil combined with HP. The addition of
      olive oil and soy sauce followed by HP decreased the amount of volatile basic
      nitrogen during storage and reduced the population of pathogens. Sensory
      evaluation indicated that the addition of olive oil enhanced the overall
      acceptance and willingness to buy. In conclusion, the combination of HP with the
      addition of soy sauce and/or olive oil is an effective technology that can
      improve chemical, health, sensory qualities and safety of chicken breast. 

PMID- 25049951
TI  - Siberian Sturgeon Oocyte Extract Induces Epigenetic Modifications of Porcine
      Somatic Cells and Improves Developmental Competence of SCNT Embryos.
AB  - Somatic cell nuclear transfer (SCNT) has generally demonstrated that a
      differentiated cell can convert into a undifferentiated or pluripotent state. In
      the SCNT experiment, nuclear reprogramming is induced by exposure of introduced
      donor nuclei to the recipient cytoplasm of matured oocytes. However, because the
      efficiency of SCNT still remains low, a combination of SCNT technique with the ex
      ovo method may improve the normal development of SCNT embryos. Here we
      hypothesized that treatment of somatic cells with extracts prepared from the
      germinal vesicle (GV) stage Siberian sturgeon oocytes prior to their use as
      nuclear donor for SCNT would improve in vitro development. A reversible
      permeability protocol with 4 MUg/mL of digitonin for 2 min at 4 degrees C in
      order to deliver Siberian sturgeon oocyte extract (SOE) to porcine fetal
      fibroblasts (PFFs) was carried out. As results, the intensity of H3K9ac staining
      in PFFs following treatment of SOE for 7 h at 18 degrees C was significantly
      increased but the intensity of H3K9me3 staining in PFFs was significantly
      decreased as compared with the control (p<0.05). Additionally, the level of
      histone acetylation in SCNT embryos at the zygote stage was significantly
      increased when reconstructed using SOE-treated cells (p<0.05), similar to that of
      IVF embryos at the zygote stage. The number of apoptotic cells was significantly
      decreased and pluripotency markers (Nanog, Oct4 and Sox2) were highly expressed
      in the blastocyst stage of SCNT embryos reconstructed using SOE-treated cells as
      nuclear donor (p<0.05). And there was observed a better development to the
      blastocyst stage in the SOE-treated group (p<0.05). Our results suggested that
      pre-treatment of cells with SOE could improve epigenetic reprogramming and the
      quality of porcine SCNT embryos. 

PMID- 25049952
TI  - Antibacterial Activity of Recombinant Pig Intestinal Parasite Cecropin P4 Peptide
      Secreted from Pichia pastoris.
AB  - Cecropins (Cec) are antibacterial peptides and their expression is induced in a
      pig intestinal parasite Ascaris suum by bacterial infection. To explore the
      usefulness of its activity as an antibiotic, CecP4 cDNA was prepared and cloned
      into the pPICZ B expression vector and followed by the integration into AOX1
      locus in Pichia pastoris. The supernatants from cell culture were collected after
      methanol induction and concentrated for the test of antimicrobial activity. The
      recombinant P. patoris having CecP4 showed antimicrobial activity when tested
      against Staphyllococcus aureus in disc diffusion assay. We selected one of the
      CecP4 clones (CecP4-2) and performed further studies with it. The growth of
      recombinant P. pastoris was optimized using various concentration of methanol,
      and it was found that 2% methanol in the culture induced more antibacterial
      activity, compared to 1% methanol. We extended the test of antimicrobial activity
      by applying the concentrated supernatant of CecP4 culture to Pseudomonas
      aeruginosa and E. coli respectively. Recombinant CecP4 also showed antimicrobial
      activity against both Pseudomona and E. coli, suggesting the broad spectrum of
      its antimicrobial activity. After improvements for the scale-up, it will be
      feasible to use recombinant CecP4 for supplementation to the feed to control
      microbial infections in young animals, such as piglets. 

PMID- 25049953
TI  - Ingestive behavior of lambs confined in individual and group stalls.
AB  - The experiment was conducted to evaluate the ingestive behavior of lambs confined
      in individual and group stalls. We used thirty-four lambs in their growing phase,
      aged an average of three months, with mean initial live weight of 17.8+/-5.2 kg.
      They were allotted in a completely randomized design with 24 animals kept in
      individual stalls and 10 animals confined as a group. The experiment lasted for a
      total of 74 days, and the first 14 days were dedicated to the animals' adaption
      to the management, facilities and diets. The data collection period lasted 60
      days, divided into three 20-d periods for the behavior evaluation. The animals
      were subjected to five days of visual observation during the experiment period,
      by the quantification of 24 h a day, with evaluations on the 15th day of each
      period and an interim evaluation consisting of two consecutive days on the 30th
      and 31st day of the experiment. The animals confined as a group consumed less
      (p<0.05) fiber. However, the animals confined individually spent less (p<0.05)
      time on feeding, rumination and chewing activities and longer in idleness.
      Therefore, the lower capacity of lambs confined in groups to select their food
      negatively affects their feeding behavior. 

PMID- 25049954
TI  - Multicarbohydrase Enzymes for Non-ruminants.
AB  - The first purpose of this review is to outline some of the background information
      necessary to understand the mechanisms of action of fibre-degrading enzymes in
      non-ruminants. Secondly, the well-known and understood mechanisms are described,
      i) eliminating the nutrient encapsulating effect of the cell wall and ii)
      ameliorating viscosity problems associated with certain Non Starch
      Polysaccharides, particularly arabinoxylans and beta-glucans. A third, indirect
      mechanism is then discussed: the activity of such enzymes in producing prebiotic
      oligosaccharides and promoting beneficial cecal fermentation. The literature
      contains a wealth of information on various non starch polysaccharide degrading
      enzyme (NSPase) preparations and this review aims to conclude by discussing this
      body of work, with reference to the above mechanisms. It is suggested that the
      way in which multi- versus single-component products are compared is often flawed
      and that some continuity should be employed in methods and terminology. 

PMID- 25049955
TI  - Genome-wide Association Study of Integrated Meat Quality-related Traits of the
      Duroc Pig Breed.
AB  - The increasing importance of meat quality has implications for animal breeding
      programs. Research has revealed much about the genetic background of pigs, and
      many studies have revealed the importance of various genetic factors. Since meat
      quality is a complex trait which is affected by many factors, consideration of
      the overall phenotype is very useful to study meat quality. For integrating the
      phenotypes, we used principle component analysis (PCA). The significant SNPs
      refer to results of the GRAMMAR method against PC1, PC2 and PC3 of 14 meat
      quality traits of 181 Duroc pigs. The Genome-wide association study (GWAS) found
      26 potential SNPs affecting various meat quality traits. The loci identified are
      located in or near 23 genes. The SNPs associated with meat quality are in or near
      five genes (ANK1, BMP6, SHH, PIP4K2A, and FOXN2) and have been reported
      previously. Twenty-five of the significant SNPs also located in meat quality
      related QTL regions, these result supported the QTL effect indirectly. Each
      single gene typically affects multiple traits. Therefore, it is a useful approach
      to use integrated traits for the various traits at the same time. This innovative
      approach using integrated traits could be applied on other GWAS of complex-traits
      including meat-quality, and the results will contribute to improving meat-quality
      of pork. 

PMID- 25049956
TI  - Expression Profiles of Cellular Retinol-binding Protein, Type II (CRBP II) in
      Erlang Mountainous Chickens.
AB  - Cellular retinol-binding protein II (CRBP II) belongs to the family of cellular
      retinol-binding proteins and plays a major role in absorption, transport, and
      metabolism of vitamin A. In addition, because vitamin A is correlated with
      reproductive performance, we measured CRBP II mRNA abundance in erlang
      mountainous chickens by real-time PCR using the relative quantification method.
      The expression of CRBP II showed a tissue-specific pattern and egg production
      rate-dependent changes. The expression was very high (p<0.05) in jejunum and
      liver, intermediate in kidney, ovary, and oviduct, and lowest (p<0.05) in heart,
      hypothalamus, and pituitary. In the hypothalamus, oviduct, ovary, and pituitary,
      CRBP II mRNA abundance were correlated to egg production rate, which increased
      from 12 wk to 32 wk, peaked at 32 wk relative to the other time points, and then
      decreased from 32 wk to 45 wk. In contrast, the expression of CRBP II mRNA in
      heart, jejunum, kidney, and liver was not different at any of the ages evaluated
      in this study. These data may help to understand the genetic basis of vitamin A
      metabolism, and suggest that CRBP II may be a candidate gene to affect egg
      production traits in chickens. 

PMID- 25049957
TI  - Association between Motilin Receptor Gene Haplotypes and Growth Traits in
      Japanese Hinai-dori Crossbred Chickens.
AB  - We previously identified quantitative trait loci (QTL) for body weight and
      average daily gain in a common region between ADL0198 (chr 1: 171.7 Mb) and
      ABR0287 (chr 1: 173.4 Mb) on chicken chromosome 1 in an F2 resource population
      produced by crossing low- and high-growth lines of the Hinai-dori breed. Motilin
      receptor (MLNR) is a candidate gene affecting growth traits in the region. In
      this study, we genotyped polymorphisms of the MLNR gene and investigated its
      association with growth traits in a Hinai-dori F2 intercross population. All the
      exons of the MLNR gene in the parental population were subjected to PCR
      amplification, nucleotide sequenced and haplotypes identified. To distinguish
      resultant diplotype individuals in the F2 population, a mismatch amplification
      mutation assay was performed. Three haplotypes (Haplotypes 1-3) were accordingly
      identified. Six genotypes produced by the combination of three haplotypes
      (Haplotype 1, 2, and 3) were examined in order to identify associations between
      MLNR haplotypes and growth traits. The data showed that Haplotype 1 was superior
      to Haplotype 2 and 3 in body weight at 10 and 14 weeks of age, average daily gain
      between 4 and 10 weeks, 10 and 14 weeks, and 0 and 14 weeks of age in female in
      F2 females. It was concluded that MLNR is a useful marker of growth traits and
      could be used to develop strategies for improving growth traits in the Hinai-dori
      breed. 

PMID- 25049958
TI  - Production of Mutated Porcine Embryos Using Zinc Finger Nucleases and a Reporter
      based Cell Enrichment System.
AB  - To facilitate the construction of genetically-modified pigs, we produced cloned
      embryos derived from porcine fibroblasts transfected with a pair of engineered
      zinc finger nuclease (ZFN) plasmids to create targeted mutations and enriched
      using a reporter plasmid system. The reporter expresses RFP and eGFP
      simultaneously when ZFN-mediated site-specific mutations occur. Thus, double
      positive cells (RFP(+)/eGFP(+)) were selected and used for somatic cell nuclear
      transfer. Two types of reporter based enrichment systems were used in this study;
      the cloned embryos derived from cells enriched using a magnetic sorting-based
      system showed better developmental competence than did those derived from cells
      enriched by flow cytometry. Mutated sequences, such as insertions, deletions, or
      substitutions, together with the wild-type sequence, were found in the cloned
      porcine blastocysts. Therefore, genetic mutations can be achieved in cloned
      porcine embryos reconstructed with ZFN-treated cells that were enriched by a
      reporter-based system. 

PMID- 25049959
TI  - Production, Nutritional Quality and In vitro Methane Production from Andropogon
      gayanus Grass Harvested at Different Maturities and Preserved as Hay or Silage.
AB  - Andropogon gayanus is an important grass due to its high biomass production,
      drought tolerance and favorable growth on low fertility acidic soils. Currently,
      there is little research on the impact of growth stage on the nutritional quality
      or the degree of CH4 production that may arise from this forage during ruminal
      fermentation. The objectives of this study were to determine the effects of
      regrowth stage of A. gayanus on its chemical composition, in vitro production of
      gas and CH4, as well as in vitro dry matter (DM) digestibility when grown under
      tropical Brazilian conditions and conserved as hay or as silage. The nutritional
      value of A. gayanus grass declined with increasing maturity; however digestible
      DM yield linearly increased. After 112 d of regrowth, A. gayanus produced higher
      quality silage (higher lactate and lower pH and butyrate content) and higher DM
      yield. However, the low levels of crude protein at this time would make protein
      supplementation a necessity for proper rumen fermentation. No differences in CH4
      kinetic parameters were found with advancing maturity or preservation method (hay
      or silage). 

PMID- 25049961
TI  - Effect of Applying Molasses and Propionic Acid on Fermentation Quality and
      Aerobic Stability of Total Mixed Ration Silage Prepared with Whole-plant Corn in
      Tibet.
AB  - The objective of this study was to evaluate the effects of molasses and propionic
      acid on the fermentation quality and aerobic stability of total mixed ration
      (TMR) silages prepared with whole-plant corn in Tibet. TMR (354 g/kg DM) was
      ensiled with four different treatments: no additive (control), molasses (M),
      propionic acid (P), and molasses+propionic acid (PM), in laboratory silos (250
      mL) and fermented for 45 d. Silos were opened and silages were subjected to an
      aerobic stability test for 12 days, in which chemical and microbiological
      parameters of TMR silages were measured to determined the aerobic deterioration.
      After 45 d of ensiling, the four TMR silages were of good quality with low pH
      value and ammonia/total N (AN), and high lactic acid (LA) content and V-scores. M
      silage showed the highest (p<0.05) LA content and higher dry matter (DM) recovery
      than the control and P silages. P silage had lower (p<0.05) LA content than the
      control silage. During aerobic exposure, lactic acid contents decreased gradually
      in the control and M silages, while that of P and PM silages increased, and the
      peak values were observed after 9 d. M silage had similar yeast counts with the
      control silage (>10(5) cfu/g FM), however, it appeared to be more stable as
      indicated by a delayed pH value increase. P and PM silages showed fewer yeasts
      (<10(5) cfu/g FM) (p<0.05) and were more stable than the control and M silages
      during aerobic exposure. It was concluded that M application increased LA content
      and improved aerobic stability of TMR silage prepared with whole-plant corn in
      Tibet. P application inhibited lactic acid production during ensiling, and
      apparently preserved available sugars which stimulated large increases in lactic
      acid during aerobic exposure stage, which resulted in greater aerobic stability
      of TMR silage. 

PMID- 25049960
TI  - Influence of Condensed Tannins from Ficus bengalensis Leaves on Feed Utilization,
      Milk Production and Antioxidant Status of Crossbred Cows.
AB  - This study was conducted to examine the effects of condensed tannins (CT) from
      Ficus bengalensis leaves on the feed utilization, milk production and health
      status of crossbred cows. Eighteen crossbred dairy cows at their second and mid
      lactation (avg. BW 351.6+/-10.6 kg) were randomly divided into two groups of nine
      each in a completely randomized block design and fed two iso-nitrogenous
      supplements formulated to contain 0% and 1.5% CT through dried and ground leaves
      of Ficus bengalensis. The diets were designated as CON and FBLM, respectively and
      fed to cows with a basal diet of rice straw to meet requirements for maintenance
      and milk production. The daily milk yield was significantly (p<0.05) increased
      due to supplementation of FBLM diet. The 4% fat corrected milk yield was also
      significantly (p<0.01) higher due to increased (p<0.05) milk fat in cows under
      diet FBLM as compared to CON. The inclusion of CT at 1.5% in the supplement did
      not interfere with the feed intake or digestibility of DM, OM, CP, EE, NDF, and
      ADF by lactating cows. Digestible crude protein (DCP) and total digestible
      nutrients (TDN) values of the composite diets were comparable between the groups.
      The blood biochemical parameters remained unaltered except significantly (p<0.05)
      lowered serum urea concentration in cows fed FBLM diet. There was a significant
      (p<0.05) increase intracellular reduced glutathione (GSH), superoxide dismutase
      (SOD) and catalase (CAT) activity in cows supplemented with condensed tannins.
      The total thiol group (T-SH) was found to be higher with reduction in lipid
      peroxidation (LPO) in cows of FBLM group. The cost of feeding per kg milk
      production was also reduced due to supplementation of Ficus bengalensis leaves.
      Therefore, a perceptible positive impact was evident on milk production and
      antioxidant status in crossbred cows during mid-lactation given supplement
      containing 1.5% CT through Ficus bengalensis leaves. 

PMID- 25049962
TI  - Nutrient Digestibility, Ruminal Fermentation Activities, Serum Parameters and
      Milk Production and Composition of Lactating Goats Fed Diets Containing Rice
      Straw Treated with Pleurotus ostreatus.
AB  - The study evaluated replacement of Egyptian berseem clover (BC, Trifolium
      alexandrinum) with spent rice straw (SRS) of Pleurotus ostreatus basidiomycete in
      diets of lactating Baladi goats. Nine lactating homo-parity Baladi goats (average
      BW 23.8+/-0.4 kg) at 7 d postpartum were used in a triplicate 3*3 Latin square
      design with 30 d experimental periods. Goats were fed a basal diet containing 0
      (Control), 0.25 (SRS25) and 0.45 (SRS45) (w/w, DM basis) of SRS. The Control diet
      was berseem clover and concentrate mixture (1:1 DM basis). The SRS45 had lowered
      total feed intake and forages intake compared to Control. The SRS25 and SRS45
      rations had the highest digestibilities of DM (p = 0.0241) and hemicellulose (p =
      0.0021) compared to Control which had higher (p<0.01) digestibilities of OM (p =
      0.0002) and CP (p = 0.0005) than SRS25 and SRS45. Ruminal pH and microbial
      protein synthesis were higher (p<0.0001) for SRS25 and SRS45 than Control, which
      also had the highest (p<0.0001) concentration of TVFA, total proteins, non
      protein N, and ammonia-N. All values of serum constituents were within normal
      ranges. The Control ration had higher serum globulin (p = 0.0148), creatinine (p
      = 0.0150), glucose (p = 0.0002) and cholesterol (p = 0.0016). Both Control and
      SRS25 groups had the highest (p<0.05) milk (p = 0.0330) and energy corrected milk
      (p = 0.0290) yields. Fat content was higher (p = 0.0373) with SRS45 and SRS25
      groups compared with Control. Replacement of BC with SRS in goat rations
      increased milk levels of conjugated linoleic acid and unsaturated fatty acids
      compared with Control. It was concluded that replacing 50% of Egyptian berseem
      clover with SRS in goat rations improved their productive performance without
      marked effects on metabolic indicators health. 

PMID- 25049963
TI  - Effects of dietary crude glycerin supplementation on nutrient digestibility,
      ruminal fermentation, blood metabolites, and nitrogen balance of goats.
AB  - This experiment was conducted to evaluate the effects of increasing
      concentrations of crude glycerin (CGLY) in diets on nutrient utilization, ruminal
      fermentation characteristics, and nitrogen utilization of goats. Four male
      crossbred (Thai Native*Anglo Nubian) goats, with an average initial weight of
      26+/-3.0 kg, were randomly assigned according to a 4*4 Latin square design with
      four 21 days consecutive periods. Treatments diets contained 0%, 5%, 10%, and 20%
      of dietary DM of CGLY. Based on this experiment, there were no significant
      differences (p>0.05) among treatment groups regarding DM intake and digestion
      coefficients of nutrients (DM, OM, CP, EE, NDF, and ADF). Likewise, mean serum
      glucose, BHBA, and PCV concentrations were not affected (p>0.05) by dietary
      treatments, whereas serum insulin concentration linearly increased (L, p = 0.002)
      with increasing the amount of CGLY supplementation. Ruminal pH, NH3-N, and BUN
      concentration were unchanged by dietary treatments, except for 20% of CGLY, NH3
      N, and BUN were lower (p<0.05) than for the diets 10% of CGLY, while the
      difference between the diets 0%, 5%, and 20% of CGLY were not significant. The
      amount of N absorption and retention were similar among treatments. Based on this
      study, CGLY levels up to 20% in total mixed ration could be efficiently utilized
      for goats and this study elucidates a good approach to exploiting the use of
      biodiesel production for goat production. 

PMID- 25049964
TI  - Effects of two herbal extracts and virginiamycin supplementation on growth
      performance, intestinal microflora population and Fatty Acid composition in
      broiler chickens.
AB  - The competency of garlic and pennywort to improve broiler chicken growth and
      influence intestinal microbial communities and fatty acid composition of breast
      meat were studied. Two hundred forty, "day-old" chicks were randomly allocated to
      4 treatment groups consisting of 6 replications of 10 chicks in each pen. The
      groups were assigned to receive treatment diets as follows: i) basal diet
      (control), ii) basal diet plus 0.5% garlic powder (GP), iii) basal diet plus 0.5%
      pennywort powder (PW) and iv) 0.002% virginiamycin (VM). Birds were killed at day
      42 and intestinal samples were collected to assess for Lactobacillus and
      Escherichia coli. The pectoralis profundus from chicken breast samples was
      obtained from 10 birds from each treatment group on day 42 and frozen at -20
      degrees C for further analyses. Fatty acid profile of breast muscles was
      determined using gas liquid chromatography. Feed intake and weight gain of
      broilers fed with GP, PW, and VM were significantly higher (p<0.05) compared to
      control. Feeding chicks GP, PW, and VM significantly reduced Escherichia coli
      count (p<0.05) while Lactobacillus spp count were significantly higher (p<0.05)
      in the gut when compared to control group on day 42. Supplemented diet containing
      pennywort increased the C18:3n-3 fatty acid composition of chickens' breast
      muscle. Garlic and pennywort may be useful in modulating broiler guts as they
      control the enteropathogens that help to utilize feed efficiently. This
      subsequently enhances the growth performances of broiler chickens. 

PMID- 25049965
TI  - Effects of Dietary Supplementation of Barodon, an Anionic Alkali Mineral Complex,
      on Growth Performance, Feed Utilization, Innate Immunity, Goblet Cell and
      Digestibility in Olive Flounder (Paralichthys olivaceus).
AB  - A 15-wk feeding trial was conducted to examine the supplemental effects of
      Barodon on growth performance, gastrointestinal histology, feed digestibility and
      innate immunity in olive founder. A basal commercial diet was used as a control
      and two other diets were prepared by spraying 0.1% or 0.2% of Barodon. Triplicate
      groups of fish (BW, 145 g) were fed one of the test diets to apparent satiation
      twice daily. At the end of the feeding trial, fish growth performance was not
      significantly affected by dietary treatments; however, feed utilization was
      significantly improved (linear and quadratic, p<0.05) by Barodon supplementation.
      Significantly higher (p<0.05) survival rates were obtained in fish fed Barodon
      containing diets. Hepatosomatic index increased significantly in Barodon treated
      groups. Also, the use of Barodon resulted in significant increase (linear and
      quadratic, p<0.05) of intestine length and number of goblet cells. Significantly
      higher (Quadratic, p<0.05) apparent digestibility coefficient of DM was obtained
      by supplementation of Barodon. Lysozyme and myeloperoxidase activities increased
      quadratically and linearly, respectively, in Barodon treated fish. Also,
      significantly higher (linear and quadratic, p<0.05) superoxide dismutase activity
      was found in Barodon fed fish. The findings in this study show that inclusion of
      Barodon in diets for olive flounder improves feed utilization and digestibility,
      and positively affects digestive tract histology and innate immunity. 

PMID- 25049966
TI  - Impact of echinococcosis on quality of sheep meat in the South eastern
      Kazakhstan.
AB  - A survey of 2,123 slaughtered adult sheep in markets of the south-east Kazakhstan
      established that the average contamination of animals by Echinococcus granulosus
      is 9.1% with primary localization of cysts in livers and lungs. The histologic
      structure of the muscle tissue of infected sheep displayed destructive changes
      with a prevalence of granular dystrophy. The amount of protein, fat, calcium and
      energetical value of such meat considerably decreased. Besides in the muscle
      tissue of the animals infected with echinococcosis there was a substantial
      increase of humidity and amount of ash as well as qualitative and quantitative
      changes of the amino acids profile. Along with damage to the synthesis of
      proteins and sharp insufficiency of vitamins A, E, B1, and B2 there was a shift
      in a lipidic exchange that was expressed as a noticeable reduction in the level
      of monounsaturated and polyunsaturated fatty acids. The data support the
      conclusion that the meat from the sheep infected with echinococcosis is of
      inferior quality and quantity compared to that of healthy animals. 

PMID- 25049967
TI  - Comparison of growth performance, carcass characteristics and meat quality of
      korean local chickens and silky fowl.
AB  - This study was conducted to compare growth performance, carcass characteristics
      and meat quality of 4 breeds of local chicken. A total of 480 1-d-old chicks were
      distributed to 16 pens, with 4 treatments of breed, 4 replicates and 30 chicks
      per pen. Three Korean local breeds of white-mini broiler, Hanhyup-3-ho, and
      Woorimatdag, and a breed of silky fowl were raised under identical rearing and
      feeding conditions for 31-d, 37-d, 36-d, and 59-d, respectively. The BW and feed
      consumption on a pen basis were weekly measured for all pens, and ADFI, ADG and
      gain:feed were calculated for each pen. The ADFI and ADG of 3 breeds of Korean
      local chicken were greater than those of silky fowl (p<0.05). Within the Korean
      local breeds, ADFI of white-mini broiler was the highest (p<0.05), and ADG of
      Hanhyup-3-ho and white-mini broiler was the highest (p<0.05). Gain:feed of silky
      fowl was less than that of the 3 breeds of Korean local chicken. The carcass and
      breast yield of white-mini broiler were the greater than those of other breeds
      (p<0.05). The breast meat color (CIE L*, a*, and b*) of 3 breeds of Korean local
      chicken were higher than that of silky fowl (p<0.05). The breast meat of Hanhyup
      3-ho had greater cooking loss (p<0.05), whereas water holding capacity and pH
      were less than those of other breeds (p<0.05). The color score of 3 breeds of
      Korean local chicken was higher than that of silky fowl (p<0.05). Woorimatdag had
      a higher score on tenderness (p<0.05), whereas flavor score was less than that of
      other breeds (p<0.05). In conclusion, 4 local breeds of chicken have some unique
      features and seem to have more advantages, and this information can help
      consumers who prefer healthy and premium chicken meat. 

PMID- 25049968
TI  - Bleeding Efficiency and Meat Oxidative Stability and Microbiological Quality of
      New Zealand White Rabbits Subjected to Halal Slaughter without Stunning and Gas
      Stun-killing.
AB  - A study was conducted to compare the effect of halal slaughter without stunning
      and gas stun killing followed by bleeding on residual blood content and storage
      stability of rabbit meat. Eighty male New Zealand white rabbits were divided into
      two groups of 40 animals each and subjected to either halal slaughter without
      stunning (HS) or gas stun-kill (GK). The volume of blood lost during
      exsanguination was measured. Residual blood was further quantified by
      determination of haemoglobin content in Longissimus lumborum (LL) muscle. Storage
      stability of the meat was evaluated by microbiological analysis and measuring
      lipid oxidation in terms of thiobarbituric acid reactive substances (TBARS). HS
      resulted in significantly higher blood loss than GK. HS had significantly lower
      residual haemoglobin in LL muscle compared to GK. Slaughter method had no effect
      on rabbit meat lipid oxidation at 0, 1, and 3 d postmortem. However, at 5 and 8
      days of storage at 4 degrees C, significant differences (p<0.05) were found, with
      meat from the GK group exhibiting significantly higher levels of MDA than that
      from HS. At day 3, greater growth of Pseudomonas aeroginosa and E. coli were
      observed in the GK group (p<0.05) with B. thermosphacta and total aerobic counts
      remained unaffected by slaughter method. At days 5 and 7 postmortem, bacterial
      counts for all tested microbes were affected by slaughter method, with GK
      exhibiting significantly higher growth than HS. It can be concluded that
      slaughter method can affect keeping quality of rabbit meat, and HS may be a
      favourable option compared to GK due to high bleed out. 

PMID- 25049969
TI  - Effects of Saturated Long-chain Fatty Acid on mRNA Expression of Genes Associated
      with Milk Fat and Protein Biosynthesis in Bovine Mammary Epithelial Cells.
AB  - This study was conducted to determine the effects of saturated long-chain fatty
      acids (LCFA) on cell proliferation and triacylglycerol (TAG) content, as well as
      mRNA expression of alphas1-casein (CSN1S1) and genes associated with lipid and
      protein synthesis in bovine mammary epithelial cells (BMECs). Primary cells were
      isolated from the mammary glands of Holstein dairy cows, and were passaged twice.
      Then cells were cultured with different levels of palmitate or stearate (0, 200,
      300, 400, 500, and 600 MUM) for 48 h and fetal bovine serum in the culture
      solution was replaced with fatty acid-free BSA (1 g/L). The results showed that
      cell proliferation tended to be increased quadratically with increasing addition
      of stearate. Treatments with palmitate or stearate induced an increase in TAG
      contents at 0 to 600 MUM in a concentration-dependent manner, and the addition of
      600 MUM was less effective in improving TAG accumulation. The expression of
      acetyl-coenzyme A carboxylase alpha, fatty acid synthase and fatty acid-binding
      protein 3 was inhibited when palmitate or stearate were added in culture medium,
      whereas cluster of differentiation 36 and CSN1S1 mRNA abundance was increased in
      a concentration-dependent manner. The mRNA expressions of peroxisome proliferator
      activated receptor gamma, mammalian target of rapamycin and signal transducer and
      activator of transcription 5 with palmitate or stearate had no significant
      differences relative to the control. These results implied that certain
      concentrations of saturated LCFA could stimulate cell proliferation and the
      accumulation of TAG, whereas a reduction may occur with the addition of an
      overdose of saturated LCFA. Saturated LCFA could up-regulate CSN1S1 mRNA
      abundance, but further studies are necessary to elucidate the mechanism for
      regulating milk fat and protein synthesis. 

PMID- 25049970
TI  - Grazing Soybean to Increase Voluntary Cow Traffic in a Pasture-based Automatic
      Milking System.
AB  - Pasture-based automatic milking systems (AMS) require cow traffic to enable cows
      to be milked. The interval between milkings can be manipulated by strategically
      allocating pasture. The current experiment investigated the effect of replacing
      an allocation of grazed pasture with grazed soybean (Glycine max) with the
      hypothesis that incorporating soybean would increase voluntary cow traffic and
      milk production. One hundred and eighty mixed age, primiparous and multiparous
      Holstein-Friesian/Illawarra cows were randomly assigned to two treatment groups
      (n = 90/group) with a 2*2 Latin square design. Each group was either offered
      treatments of kikuyu grass (Pennisetum clandestinum Hoach ex Chiov.) pasture
      (pasture) or soybean from 0900 h to 1500 h during the experimental period which
      consisted of 2 periods of 3 days following 5 days of training and adaptation in
      each period with groups crossing over treatments after the first period. The
      number of cows trafficking to each treatment was similar together with milk yield
      (mean ~18 L/cow/d) in this experiment. For the cows that arrived at soybean or
      pasture there were significant differences in their behaviour and consequently
      the number of cows exiting each treatment paddock. There was greater cow traffic
      (more cows and sooner) exiting pasture allocations. Cows that arrived at soybean
      stayed on the allocation for 25% more time and ate more forage (8.5
      kg/cow/d/allocation) relative to pasture (4.7 kg/cow/d/allocation). Pasture cows
      predominantly replaced eating time with rumination. These findings suggest that
      replacing pasture with alternative grazeable forages provides no additional
      incentive to increase voluntary cow traffic to an allocation of feed in AMS. This
      work highlights the opportunity to increase forage intakes in AMS through the
      incorporation of alternative forages. 

PMID- 25049971
TI  - Piglets' surface temperature change at different weights at birth.
AB  - The study was carried out in order to verify the effects of piglets' weight at
      birth on their surface temperature change (ST) after birth, and its relationship
      with ingestion time of colostrum. Piglets from four different sows were weighed
      at birth and divided into a totally randomized design with three treatments
      according to birth weight (PBW): T1 - less than 1.00 kg, T2 - 1.00 to 1.39 kg,
      and T3 - higher than or equal to 1.40 kg. The time spent for the first colostrum
      ingestion was recorded (TFS). Images of piglets' surface by thermal imaging
      camera were recorded at birth (STB) and 15, 30, 45, 60, and 120 min after birth.
      The air temperature and relative humidity were recorded every 30 min and the
      indexes of temperature and humidity (THI) were calculated. A ST drop after 15 min
      from birth was observed, increasing again after sixty minutes. Positive
      correlations were found between the PBW and the ST at 30 and 45 min after birth.
      The PBW was negatively correlated with the TFS. The THI showed high negative
      correlations (-0.824 and -0.815) with STB and after 15 min from birth. The
      piglet's surface temperature at birth was positively correlated with temperature
      thereof to 15 min, influencing therefore the temperatures in the interval of 45
      to 120 min. The birth weight contributes significantly to postnatal hypothermia
      and consequently to the time it takes for piglets ingest colostrum, requiring
      special attention to those of low birth weight. 

PMID- 25049972
TI  - Data Build-up for the Construction of Korean Specific Greenhouse Gas Emission
      Inventory in Livestock Categories.
AB  - Many studies on methane (CH4) and nitrous oxide (N2O) emissions from livestock
      industries have revealed that livestock production directly contributes to
      greenhouse gas (GHG) emissions through enteric fermentation and manure
      management, which causes negative impacts on animal environment sustainability.
      In the present study, three essential values for GHG emission were measured;
      i.e., i) maximum CH4 producing capacity at mesophilic temperature (37 degrees C)
      from anaerobically stored manure in livestock category (B0,KM, Korean livestock
      manure for B0), ii) EF3(s) value representing an emission factor for direct N2O
      emissions from manure management system S in the country, kg N2O-N kg N(-1), at
      mesophilic (37 degrees C) and thermophilic (55 degrees C) temperatures, and iii)
      Nex(T) emissions showing annual N excretion for livestock category T, kg N
      animal(-1) yr(-1), from different livestock manure. Static incubation with and
      without aeration was performed to obtain the N2O and CH4 emissions from each
      sample, respectively. Chemical compositions of pre- and post-incubated manure
      were analyzed. Contents of total solids (% TS) and volatile solid (% VS), and the
      ratio of carbon to nitrogen (C/N) decrease significantly in all the samples by C
      containing biogas generation, whereas moisture content (%) and pH increased after
      incubation. A big difference of total nitrogen content was not observed in pre-
      and post-incubation during CH4 and N2O emissions. CH4 emissions (g CH4 kg VS(-1))
      from all the three manures (sows, layers and Korean cattle) were different and
      high C/N ratio resulted in high CH4 emission. Similarly, N2O emission was found
      to be affected by % VS, pH, and temperature. The B0,KM values for sows, layers,
      and Korean cattle obtained at 37 degrees C are 0.0579, 0.0006, and 0.0828 m(3)
      CH4 kg VS(-1), respectively, which are much less than the default values in IPCC
      guideline (GL) except the value from Korean cattle. For sows and Korean cattle,
      Nex(T) values of 7.67 and 28.19 kg N yr(-1), respectively, are 2.5 fold less than
      those values in IPCC GL as well. However, Nex(T) value of layers 0.63 kg N yr(-1)
      is very similar to the default value of 0.6 kg N yr(-1) in IPCC GLs for National
      greenhouse gas inventories for countries such as South Korea/Asia. The EF3(s)
      value obtained at 37 degrees C and 55 degrees C were found to be far less than
      the default value. 

PMID- 25049973
TI  - Efficacy of carcass electrical stimulation in meat quality enhancement: a review.
AB  - The use of electrical stimulation (ES) as a management tool to improve meat
      quality and efficiency of meat processing is reviewed. The basis of the efficacy
      of ES is its ability to fast track postmortem glycolysis, which in turn
      stimulates myriad histological, physical, biochemical, biophysical and
      physiological changes in the postmortem muscle. Electrical stimulation hastens
      the onset and resolution of rigor mortis thereby reducing processing time and
      labor and plays a vital role in improving meat tenderness and other meat quality
      traits. However, ES may have negative impacts on some meat quality traits such as
      color stability and water holding capacity in some animals. Electrical
      stimulation is not an end in itself. In order to achieve the desired benefits
      from its application, the technique must be properly used in conjunction with
      various intricate antemortem, perimortem and postmortem management practices.
      Despite extensive research on ES, the fundamental mechanisms and the appropriate
      commercial applications remained obscured. In addition, muscles differ in their
      response to ES. Thus, elementary knowledge of the various alterations with
      respect to muscle type is needed in order to optimize the effectiveness of ES in
      the improvement of meat quality. 

PMID- 25049974
TI  - Genetic analysis of ultrasound and carcass measurement traits in a regional
      hanwoo steer population.
AB  - Ultrasound measurements of backfat thickness (UBF), longissimus muscle area
      (ULMA) and marbling score (UMS) and carcass measurements of carcass weight (CW),
      backfat thickness (BF), longissimus muscle area (LMA), and marbling score (MS) on
      7,044 Hanwoo steers were analyzed to estimate genetic parameters. Data from
      Hanwoo steers that were raised, finished in Hoengseong-gun, Gangwon-do (province)
      and shipped to slaughter houses during the period from October 2010 to April 2013
      were evaluated. Ultrasound measurements were taken at approximately three months
      before slaughter by an experienced operator using a B-mode real-time ultrasound
      device (HS-2000, FHK Co. Ltd., Tokyo, Japan) with a 3.5 MHz linear probe.
      Ultrasound scanning was on the left side between 13th rib and the first lumbar
      vertebrae. All slaughtering processes and carcass evaluations were performed in
      accordance with the guidelines of beef grading system of Korea. To estimate
      genetic parameters, multiple trait animal models were applied. Fixed effects
      included in the models were: the effects of farm, contemporary group effects
      (year-season at the time of ultrasound scanning in the models for UBF, ULMA, and
      UMS, and year-season at slaughter in the models for CW, BF, LMA, and MS), the
      effects of ultrasound technicians as class variables and the effects of the age
      in days at ultrasound scanning or at slaughtering as linear covariates,
      respectively for ultrasound and carcass measures. Heritability estimates obtained
      from our analyses were 0.37 for UBF, 0.13 for ULMA, 0.27 for UMS, 0.44 for CW,
      0.33 for BF, 0.36 for LMA and 0.54 MS, respectively. Genetic correlations were
      strongly positive between corresponding traits of ultrasound and carcass
      measures. Genetic correlation coefficient between UBF and BF estimate was 0.938,
      between ULMA and LMA was 0.767 and between UMS and MS was 0.925. These results
      suggest that ultrasound measurement traits are genetically similar to carcass
      measurement traits. 

PMID- 25049975
TI  - Differential Evolution between Monotocous and Polytocous Species.
AB  - One of the most important traits for both animal science and livestock production
      is the number of offspring for a species. This study was performed to identify
      differentially evolved genes and their distinct functions that influence the
      number of offspring at birth by comparative analysis of eight monotocous mammals
      and seven polytocous mammals in a number of scopes: specific amino acid
      substitution with site-wise adaptive evolution, gene expansion and specific
      orthologous group. The mutually exclusive amino acid substitution among the 16
      mammalian species identified five candidate genes. These genes were both directly
      and indirectly related to ovulation. Furthermore, in monotocous mammals, the EPH
      gene family was found to have undergone expansion. Previously, the EPHA4 gene was
      found to positively affect litter size in pigs and supports the possibility of
      the EPH gene playing a role in determining the number of offspring per birth. The
      identified genes in this study offer a basis from which the differences between
      monotocous and polytocous species can be studied. Furthermore, these genes may
      harbor some clues to the underlying mechanism, which determines litter size and
      may prove useful for livestock breeding strategies. 

PMID- 25049976
TI  - Selection of Reference Genes for Gene Expression Studies in Porcine Whole Blood
      and Peripheral Blood Mononuclear Cells under Polyinosinic:Polycytidylic Acid
      Stimulation.
AB  - Investigating gene expression of immune cells of whole blood or peripheral blood
      mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C)
      stimulation is valuable for understanding the immune response of organism to RNA
      viruses. Quantitative real-time PCR (qRT-PCR) is a standard method for
      quantification of gene expression studies. However, the reliability of qRT-PCR
      data critically depends on proper selection of reference genes. In the study,
      using two different analysis programs, geNorm and NormFinder, we systematically
      evaluated the gene expression stability of six candidate reference genes (GAPDH,
      ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or
      without poly I:C stimulation. Generally, the six candidate genes performed a
      similar trend of expression stability in the samples of whole blood and PBMC, but
      more stably expressed in whole blood than in PBMC. geNorm ranked B2M and PPIA as
      the best combination for gene expression normalization, while according to
      NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and
      PPIA. Comprehensively considering the results from the two programs, we
      recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to
      normalize the gene expression of whole blood and PBMC with poly I:C stimulation.
      Our study is the first detailed survey of the gene expression stability in whole
      blood and PBMC with or without poly I:C stimulation and should be helpful for
      investigating the molecular mechanism involved in porcine whole blood and PBMC in
      response to poly I:C stimulation. 

PMID- 25049977
TI  - The Expression of Leptin, Estrogen Receptors, and Vitellogenin mRNAs in Migrating
      Female Chum Salmon, Oncorhynchus keta: The Effects of Hypo-osmotic Environmental
      Changes.
AB  - Leptin plays an important role in energy homeostasis and reproductive function in
      fish, especially in reproduction. Migrating fish, such as salmonoids, are
      affected by external environmental factors, and salinity changes are a
      particularly important influence on spawning migrations. The aim of this study
      was to test whether changes in salinity affect the expression of leptin, estrogen
      receptors (ERs), and vitellogenin (VTG) in chum salmon (Oncorhynchus keta). The
      expression and activity of leptin, the expression of ERs and VTG, and the levels
      of estradiol-17beta and cortisol increased after the fish were transferred to FW,
      demonstrating that changes in salinity stimulate the HPG axis in migrating female
      chum salmon. These findings reveal details about the role of elevated leptin
      levels and sex steroid hormones in stimulating sexual maturation and reproduction
      in response to salinity changes in chum salmon. 

PMID- 25049978
TI  - Effects of copper and selenium supplementation on performance and lipid
      metabolism in confined brangus bulls.
AB  - Twenty-eight Brangus cattle were used to determine the effect of copper and
      selenium supplementation on performance, feed efficiency, composition of fatty
      acids in Longissimus dorsi (LD) muscle, and cholesterol concentration in serum
      and in LD muscle and enzymes activities, reduced glutathione (GSH) and oxidized
      glutathione (GSSG). The treatments were: i) Control, without copper (Cu) and
      selenium (Se) supplementation; ii) Se, 2 mg Se/kg of dry matter such as sodium
      selenite; iii) Cu, 40 mg Cu/kg of dry matter such as copper sulfate; iv) Se/Cu, 2
      mg Se/kg of dry matter such as sodium selenite and 40 mg Cu/kg of dry matter such
      as copper sulfate. LD muscle fatty acid composition was not influenced by the
      treatments (p>0.05). The serum concentration of cholesterol was not influenced by
      the treatments (p>0.05), however, the concentration of cholesterol in LD was
      lower in cattle supplemented with copper and selenium (p<0.05). Oxidized
      glutathione and reduced glutathione increased (p<0.05) with Cu, Se and Se/Cu
      supplementation. The supplementation of copper (40 mg/kg DM) and selenium (2
      mg/kg DM) altered the metabolism of lipids in confined Brangus cattle, through a
      decrease in cholesterol deposition in the LD, possibly by changing the ratio
      between reduced glutathione/oxidized glutathione. Copper and selenium
      supplementation improved animal performance and feed efficiency (p<0.05) when
      compared to the control group, providing advantages in the production system,
      while also benefiting consumers by reducing cholesterol concentration in the
      meat. 

PMID- 25049979
TI  - Effect of Feeding Bacillus subtilis natto on Hindgut Fermentation and Microbiota
      of Holstein Dairy Cows.
AB  - The effect of Bacillus subtilis natto on hindgut fermentation and microbiota of
      early lactation Holstein dairy cows was investigated in this study. Thirty-six
      Holstein dairy cows in early lactation were randomly allocated to three groups:
      no B. subtilis natto as the control group, B. subtilis natto with 0.5*10(11) cfu
      as DMF1 group and B. subtilis natto with 1.0*10(11) cfu as DMF2 group. After 14
      days of adaptation period, the formal experiment was started and lasted for 63
      days. Fecal samples were collected directly from the rectum of each animal on the
      morning at the end of eighth week and placed into sterile plastic bags. The pH,
      NH3-N and VFA concentration were determined and fecal bacteria DNA was extracted
      and analyzed by DGGE. The results showed that the addition of B. subtilus natto
      at either treatment level resulted in a decrease in fecal NH3-N concentration but
      had no effect on fecal pH and VFA. The DGGE profile revealed that B. subtilis
      natto affected the population of fecal bacteria. The diversity index of Shannon
      Wiener in DFM1 decreased significantly compared to the control. Fecal Alistipes
      sp., Clostridium sp., Roseospira sp., beta proteobacterium were decreased and
      Bifidobacterium was increased after supplementing with B. subtilis natto. This
      study demonstrated that B. subtilis natto had a tendency to change fecal
      microbiota balance. 

PMID- 25049980
TI  - Growth Performance, Carcass Characteristics and Meat Yield of Boer Goats Fed
      Diets Containing Leaves or Whole Parts of Andrographis paniculata.
AB  - The study was conducted to determine the effect of feeding diets containing
      Andrographis paniculata leaves (APL), whole Andrographis paniculata plant (APWP)
      and a control without Andrographis paniculata (AP0), on growth performance,
      carcass characteristics and meat yield of 24 intact Boer bucks. The results
      obtained indicated that inclusion of Andrographis paniculata significantly
      improved feed intake, weight gain, feed efficiency and live weight. The ratios of
      carcass to fat, lean to bone, lean to fat, and composition of meat were also
      improved. In addition, there were significant differences (p<0.05) between the
      dietary treatments in dressing percentage and chilling loss. Goats fed on AP0
      (control) had significantly higher proportions of fat and bone, as well as
      thicker back fat than the supplemented animals (APL and APWP). Higher gut fill in
      animals fed Andrographis paniculata suggested slow rate of digestion, which could
      have improved utilization and absorption of nutrients by the animals. Goats fed
      Andrographis paniculata also produced higher meat yield and relatively lower fat
      contents (p<0.05). 

PMID- 25049981
TI  - Effects of microbial additives on chemical composition and fermentation
      characteristics of barley silage.
AB  - This study examined the effects of bacterial inoculants on chemical composition
      and fermentation indices of barley silage. Barley forage (Youngyang) was
      harvested at 24% dry matter (DM) and wilted to 47.9% DM. The wilted barley forage
      was chopped to 3-5 cm length and applied with no inoculant (CON), L. plantarum
      (1*10(10) cfu/g, LP) or Effective Microorganisms (0.5*10(9) cfu/g, EM). Then the
      forages were ensiled in four replications for each treatment in 20 L mini silos
      and stored for 100 days. The contents of crude protein and ether extract were
      higher in CON silage ensiled for 100-d, while the contents of DM and crude ash
      were higher in EM silage (p<0.05). The contents of ADF, NDF and hemicellulose as
      well as the in vitro DM digestibility were not affected by microbial inoculation
      (p>0.05). The pH, ammonia-N concentration and lactate to acetate ratio were
      higher (p<0.05) in CON silage, while lactate concentrations were higher (p<0.05)
      in CON and LP silage. Acetate concentration and lactic acid bacteria was
      increased (p<0.05) by both inoculants (LP and EM), but propionate concentration
      and yeast was increased (p<0.05) by EM and LP, respectively. These results
      indicated that the fermentation quality of barley silage was improved by the
      application of bacterial inoculants. 

PMID- 25049982
TI  - Growth performance and carcass characteristics of korean native ducks fed diets
      with varying levels of limiting amino acids.
AB  - There are multiple experiments conducted with male Korean native ducks (KND) to
      evaluate the optimal levels of limiting amino acids (AA). In Exp. 1, a total of
      450 one-d-old male KNDs were divided into five groups with six replicates and fed
      experimental diets with varying levels of lysine, total sulfur amino acids (TSAA)
      and threonine (T1, 0.90/0.74/0.70%; T2, 1.00/0.82/0.77%; T3, 1.10/0.90/0.85%; T4,
      1.20/0.98/0.93%; T5, 1.30/1.07/1.01%) to 21 d of age. In Exp. 2, one-d-old male
      KND were received and fed commercial starter diet from hatching to 21 d of age,
      and then divided into five groups with six replicates and fed one of five diets
      varying levels of lysine, TSAA, and threonine (T1, 0.73/0.62/0.54%; T2,
      0.80/0.68/0.60%; T3, 0.87/0.74/0.65%; T4, 0.94/0.80/0.70%; T5, 1.01/0.86/0.75%)
      during 22 to 56 d of age, respectively. The BW gain was linearly increased as
      dietary limiting AA levels increased to 1.20% lysine, 0.98% TSAA and 0.93%
      threonine. There were no significant differences in feed intake, gain:feed and
      uniformity among groups. In Exp. 2, the BW gain and gain:feed were not affected
      by dietary limiting AA levels. There were no significant differences in carcass
      characteristics and meat quality among groups. The growth performance and carcass
      characteristics did not show the significant response to increasing dietary
      limiting AA levels in KND during 22 to 56 d of age. In conclusion, the levels of
      lysine, TSAA and threonine necessary to maximize growth for starter phase were at
      least 1.20%, 0.98%, and 0.93%, respectively. On the other hands, KND require
      relatively low levels of limiting AA for late growth and carcass yield. The
      dietary levels of 0.73% lysine, 0.62% TSAA and 0.54% threonine appear to be
      adequate during growing phase. 

PMID- 25049983
TI  - Determination of tropical forage preferences using two offering methods in
      rabbits.
AB  - Two methods of feed preference trials were compared to evaluate the acceptability
      of 5 fresh foliages: Leucaena leucocephala, Moringa oleifera, Portulaca oleracea,
      Guazuma ulmifolia, and Brosimum alicastrum that was included as control. The
      evaluation included chemical analyses and forage intake by rabbits. The first
      method was a cafeteria trial; 12 California growing rabbits aged 8 wk, allocated
      in individual cages, were offered the five forage plants at the same time inside
      the cage, while in the second trial 60 California growing rabbits aged 8 wk,
      allocated individually, were randomly distributed into 5 experimental groups (n =
      12/group); for each group just one forage species was offered at a time. The
      testing period for each method lasted for 7 d, preceded by one week of
      adaptation. The results showed that B. alicastrum and L. lecocephala were the
      most preferred forages while on the contrary G. ulmifolia was the least preferred
      one by rabbits. The results also revealed that the CV% value for the 2nd method
      (16.32%), which the tested forages were presented separately to rabbits, was
      lower and methodologically more acceptable than such value for the 1(st) method
      (34.28%), which all forages were presented together at the same time. It can be
      concluded that a range of tropical forages were consumed in acceptable quantities
      by rabbits, suggesting that diets based on such forages with a concentrate
      supplement could be used successfully for rabbit production. However, growth
      performance studies are still needed before recommendations could be made on
      appropriate ration formulations for commercial use. 

PMID- 25049984
TI  - Effects of benzoic Acid and dietary calcium:phosphorus ratio on performance and
      mineral metabolism of weanling pigs.
AB  - In a 2*2 factorial experiment the hypotheses tested were that the metabolic acid
      load caused by benzoic acid (BA) added to the feed affects bone mineralization of
      weanling pigs, and that a wide dietary calcium (Ca) to phosphorus (P) ratio in
      phytase-supplemented feeds with a marginal P concentration has a positive effect
      on bone mineralization. The four experimental diets, which contained 0.4% P and
      were supplemented with 1,000 FTU phytase/kg, contained either 5 g BA/kg or no BA
      and either 0.77% Ca or 0.57% Ca. The 68 four-week-old Large White pigs were fed
      the experimental diets ad libitum for six weeks and were then slaughtered.
      Benzoic acid increased feed intake (p = 0.009) and growth rate (p = 0.051), but
      did not influence the feed conversion ratio (p>0.10). Benzoic acid decreased the
      pH of the urine (p = 0.031), but did not affect breaking strength and
      mineralization of the tibia (p>0.10). The wide Ca:P ratio decreased feed intake
      (p = 0.034) and growth rate (p = 0.007) and impaired feed the conversion ratio (p
      = 0.027), but increased the mineral concentration in the fat-free DM of the tibia
      (p = 0.013) without influencing its breaking strength (p>0.10). The observed
      positive effect of the wide Ca:P ratio on bone mineralization may be attributed,
      at least in part, to the impaired feed conversion ratio, i.e. to the higher feed
      intake and consequently to the higher mineral intake per kg BW gain. The negative
      impact on animal performance of the wide dietary Ca:P ratio outweighs its
      potentially positive effect on bone mineralization, precluding its implementation
      under practical feeding conditions. 

PMID- 25049985
TI  - Cholesterol Removal from Whole Egg by Crosslinked beta-Cyclodextrin.
AB  - This study was carried out to optimize cholesterol removal in whole egg using
      crosslinked beta-cyclodextrin (beta-CD) and to recycle the beta-CD. Various
      factors for optimizing conditions were concentration of the beta-CD, mixing
      temperature, mixing time, mixing speed and centrifugal speed. In the result of
      this study, the optimum conditions of cholesterol removal were 25% crosslinked
      beta-CD, 40 degrees C mixing temperature, 30 min mixing time, 1,200 rpm mixing
      speed and 2,810*g centrifugal speed. The recycling was repeated five times. The
      cholesterol removal was 92.76% when treated with the optimum conditions. After
      determining the optimum conditions, the recyclable yields of the crosslinked beta
      CD ranged from 86.66% to 87.60% in the recycling and the percentage of
      cholesterol removal was over 80% until third recycling. However, the cholesterol
      removal efficiency was decreased when the number of repeated recycling was
      increased. Based on the result of this study, it was concluded that the
      crosslinked beta-CD was efficient for cholesterol removal in whole egg, and
      recycling is possible for only limited repeating times due to the interaction of
      the beta-CD and egg protein. 

PMID- 25049986
TI  - Fatty Acid Profiles of Supraspinatus, Longissimus lumborum and Semitendinosus
      Muscles and Serum in Kacang Goats Supplemented with Inorganic Selenium and
      Iodine.
AB  - Fat and fatty acids in muscle and adipose tissues are among the major factors
      influencing meat quality particularly nutritional value and palatability. The
      present study was carried out to examine the effects of supplementing inorganic
      selenium (Se), iodine (I) and a combination of both on fatty acid compositions in
      serum, and supraspinatus (SS), longissimus lumborum (LL), and semitendinosus (ST)
      muscles in goats. Twenty-four, 7 to 8 months old, Kacang male goats with a mean
      live weight of 22.00+/-1.17 kg were individually and randomly assigned into four
      groups of six animals each for 100 d of feeding prior to slaughter. The animals
      were offered the same concentrate (basal) diet as 1% of body weight with ad
      libitum amount of fresh guinea grass. The four groups were as follows: T1
      (control) - basal diet without supplementation; T2 - basal diet with 0.6 mg Se/kg
      DM; T3 - basal diet with 0.6 mg I/kg DM; T4 - basal diet with combination of 0.6
      mg Se/kg DM and 0.6 mg I/kg DM. The major fatty acids (FAs) detected in the serum
      were palmitic (C16:0), stearic (C18:0), oleic (C18:1n9) and linoleic (C18:2n-6),
      while the major FAs in the selected muscles were C16:0, C18:0 and C18:1n9 acids.
      The main polyunsaturated fatty acids (PUFA) detected in muscles and serum were
      (CI8:2n-6), linolenic acid (C18:3n-3), and arachidonic acid (C20:4n-6). No
      significant differences (p>0.05) were observed in the concentration of total
      saturated fatty acids (SFA) among the four groups. PUFA concentrations in the
      goats supplemented with Se (T2) were significantly higher (p<0.05) than the goats
      of the control group (T1). The PUFA: SFA ratio was significantly higher in the
      animals supplemented with dietary Se (T2) than those of control ones (T1). It is
      concluded that dietary supplementation of inorganic Se increased the unsaturated
      fatty acids in muscle. The supplementation of iodine with or without Se had
      negligible effects on muscle fatty acid content of Kacang crossbred male goats. 

PMID- 25049987
TI  - Carcass Characteristics and Meat Quality of Swamp Buffaloes (Bubalus bubalis)
      Fattened at Different Feeding Intensities.
AB  - Twenty-four male 1-year old swamp buffaloes (Bubalus bubalis) were randomly
      allocated to 4 groups. One group grazed on guinea grass (GG) and another on
      guinea grass and the legume Stylosanthes guianensis (GL). The other two groups
      were kept in pens and fed freshly cut guinea grass and concentrate at an amount
      of 1.5% (GC1.5) and 2.0% (GC2.0) of body weight, respectively. The effect of the
      different feeding intensities on carcass characteristics and meat quality were
      assessed. The mean body weight at slaughter was 398 (+/-16) kg. Average daily
      gain was higher in concentrate-supplemented groups (570 and 540 g/d in GC1.5 and
      GC2.0, respectively) when compared to GG (316 g/d) and GL (354 g/d) (p<0.01).
      Likewise, the warm carcass weight was higher in GC1.5 and GC2.0 compared to GG
      and GL. Dressing percentage was 48.1% and 49.5% in GC1.5 and GC2.0 in comparison
      to 42.9% and 44.8% observed in GG and GL, respectively. Meat of Longissimus
      throracis from GC1.5 and GC2.0 was redder in color (p<0.01), while water holding
      capacity (drip and thawing loss) was improved in pasture-fed groups (p<0.05).
      Protein and fat content of Longissimus thoracis was higher in animals
      supplemented with concentrate (p<0.01), as was cholesterol content (p<0.05),
      whereas PUFA:SFA ratio was higher and n-6/n-3 ratio lower (p<0.01) in pasture-fed
      buffaloes. Results of the present study showed that the supplementation of
      pasture with concentrate enhances the growth and carcass characteristics of swamp
      buffaloes expressed in superior dressing percentage, better muscling, and redder
      meat with a higher content of protein and fat, whereas animals grazing only on
      pasture had a more favorable fatty acid profile and water holding capacity. In
      conclusion, the supplementation of concentrate at a rate of about 1.5% of body
      weight is recommended to improve the performance and carcass quality of
      buffaloes. 

PMID- 25049988
TI  - Cloning and Sequence Analysis of Wild Argali ISG15 cDNA.
AB  - The complete coding sequence of Wild Argali ISG15 cDNA was generated by rapid
      amplification of cDNA ends. The ISG15 cDNA was 642 bp with an open reading frame
      of 474 bp, which encoded a 17.47 kDa protein composed of 157 amino acids. Its
      amino acid sequence shared 97.9%, 80.8%, 91.4%, 94.3%, 78.3% identity with those
      of ISG15cDNA from Ovis aries (accession no. NM001009735.1), Capra hircus
      (accession no. HQ329186.1), Bos taurus (accession no. BC102318.1), Bubalus
      bubalis (accession no. HM543269.1), and Sus scrofa (accession no. EU647216.1),
      respectively. The entire coding sequence was inserted into the pET-28a vector and
      expressed in E. coli. The recombinant protein corresponded to the expected
      molecular mass of 25 kDa as judged by SDS-PAGE, and it was detected in the
      bacterial inclusion bodies. The expressed protein could be purified by Ni(2+)
      chelate affinity chromatography and the results from the lymphocyte proliferation
      test showed that the product could stimulate lymphocyte proliferation very well
      (p<0.05), which further confirmed its biological activity. 

PMID- 25049989
TI  - Dexamethasone and acetate modulate cytoplasmic leptin in bovine preadipocytes.
AB  - Hormonal and nutrient signals regulate leptin synthesis and secretion. In
      rodents, leptin is stored in cytosolic pools of adipocytes. However, not much
      information is available regarding the regulation of intracellular leptin in
      ruminants. Recently, we demonstrated that leptin mRNA was expressed in bovine
      intramuscular preadipocyte cells (BIP cells) and that a cytoplasmic leptin pool
      may be present in preadipocytes. In the present study, we investigated the
      expression of cytoplasmic leptin protein in BIP cells during differentiation as
      well as the effects of various factors added to the differentiation medium on its
      expression in BIP cells. Leptin mRNA expression was observed only at 6 and 8 days
      after adipogenic induction, whereas the cytoplasmic leptin concentration was the
      highest on day 0 and decreased gradually thereafter. Cytoplasmic leptin was
      detected at 6 and 8 days after adipogenic induction, but not at 4 days after
      adipogenic induction. The cytoplasmic leptin concentration was reduced in BIP
      cells at 4 days after treatment with dexamethasone, whereas cytoplasmic leptin
      was not observed at 8 days after treatment. In contrast, acetate significantly
      enhanced the cytoplasmic leptin concentration in BIP cells at 8 days after
      treatment, although acetate alone did not induce adipocyte differentiation in BIP
      cells. These results suggest that dexamethasone and acetate modulate the
      cytoplasmic leptin concentration in bovine preadipocytes. 

PMID- 25049990
TI  - Expression, Purification, and Characteristic of Tibetan Sheep Breast Lysozyme
      Using Pichia pastoris Expression System.
AB  - A lysozyme gene from breast of Tibetan sheep was successfully expressed by
      secretion using a-factor signal sequence in the methylotrophic yeast, Pichia
      pastoris GS115. An expression yield and specific activity greater than 500 mg/L
      and 4,000 U/mg was obtained. Results at optimal pH and temperature showed
      recombinant lysozyme has higher lytic activity at pH 6.5 and 45 degrees C. This
      study demonstrates the successful expression of recombinant lysozyme using the
      eukaryotic host organism P. pastoris paving the way for protein engineering.
      Additionally, this study shows the feasibility of subsequent industrial
      manufacture of the enzyme with this expression system together with a high purity
      scheme for easy high-yield purification. 

PMID- 25049991
TI  - Bacillus subtilis Protects Porcine Intestinal Barrier from Deoxynivalenol via
      Improved Zonula Occludens-1 Expression.
AB  - Intestinal epithelial cells (IECs) forming the barrier for the first-line of
      protection are interconnected by tight junction (TJ) proteins. TJ alteration
      results in impaired barrier function, which causes potentially excessive
      inflammation leading to intestinal disorders. It has been suggested that toll
      like receptor (TLR) 2 ligands and some bacteria enhance epithelial barrier
      function in humans and mice. However, no such study has yet to be claimed in
      swine. The aim of the present study was to examine whether Bacillus subtilis
      could improve barrier integrity and protection against deoxynivalenol (DON)
      induced barrier disruption in porcine intestinal epithelial cell line (IPEC-J2).
      We found that B. subtilis decreased permeability of TJ and improved the
      expression of zonula occludens (ZO)-1 and occludin during the process of forming
      TJ. In addition, ZO-1 expression of IPEC-J2 cells treated with B. subtilis was up
      regulated against DON-induced damage. In conclusion, B. subtilis may have
      potential to enhance epithelial barrier function and to prevent the cells from
      DON-induced barrier dysfunction. 

PMID- 25049992
TI  - Differences in Voluntary Cow Traffic between Holstein and Illawarra Breeds of
      Dairy Cattle in a Pasture-based Automatic Milking System.
AB  - Automatic milking systems (AMS) rely upon voluntary cow traffic (the voluntary
      movement of cattle around a farm) for milk harvesting and feed consumption.
      Previous research on conventional milking systems has shown differences between
      dairy cow breeds for intake and milk production, however, the ability to
      manipulate voluntary cow traffic and milking frequency on AMS farms through breed
      selection is unknown. This study investigated the effect of breed (Holstein
      Friesian versus Illawarra) on voluntary cow traffic as determined by gate passes
      at the Camden AMS research farm dairy facility. Daily data on days in milk, milk
      yield, gate passes and milking frequency for 158 Holstein Friesian cows and 24
      Illawarra cows were collated by month for the 2007 and 2008 years. Illawarra cows
      had 9% more gate passes/day than Holstein cows over the duration of the study;
      however, the milking frequency and milk yield of both breeds were similar. Gate
      passes were greatest for both breeds in early lactation and in the winter (June
      to August) and summer (December to February) seasons. These findings highlight an
      opportunity to translate increased voluntary cow movement associated with breed
      selection into increased milking frequencies, milk production and overall pasture
      based AMS performance. 

PMID- 25049993
TI  - Trends and Projected Estimates of GHG Emissions from Indian Livestock in
      Comparisons with GHG Emissions from World and Developing Countries.
AB  - This study presents trends and projected estimates of methane and nitrous oxide
      emissions from livestock of India vis-a-vis world and developing countries over
      the period 1961 to 2010 estimated based on IPCC guidelines. World enteric methane
      emission (EME) increased by 54.3% (61.5 to 94.9 *10(9) kg annually) from the year
      1961 to 2010, and the highest annual growth rate (AGR) was noted for goat (2.0%),
      followed by buffalo (1.57%) and swine (1.53%). Global EME is projected to
      increase to 120*10(9) kg by 2050. The percentage increase in EME by Indian
      livestock was greater than world livestock (70.6% vs 54.3%) between the years
      1961 to 2010, and AGR was highest for goat (1.91%), followed by buffalo (1.55%),
      swine (1.28%), sheep (1.25%) and cattle (0.70%). In India, total EME was
      projected to grow by 18.8*10(9) kg in 2050. Global methane emission from manure
      (MEM) increased from 6.81 *10(9) kg in 1961 to 11.4*10(9) kg in 2010 (an increase
      of 67.6%), and is projected to grow to 15*10(9) kg by 2050. In India, the annual
      MEM increased from 0.52*10(9) kg to 1.1*10(9) kg (with an AGR of 1.57%) in this
      period, which could increase to 1.54*10(9) kg in 2050. Nitrous oxide emission
      from manure in India could be 21.4*10(6) kg in 2050 from 15.3*10(6) kg in 2010.
      The AGR of global GHG emissions changed a small extent (only 0.11%) from
      developed countries, but increased drastically (1.23%) for developing countries
      between the periods of 1961 to 2010. Major contributions to world GHG came from
      cattle (79.3%), swine (9.57%) and sheep (7.40%), and for developing countries
      from cattle (68.3%), buffalo (13.7%) and goat (5.4%). The increase of GHG
      emissions by Indian livestock was less (74% vs 82% over the period of 1961 to
      2010) than the developing countries. With this trend, world GHG emissions could
      reach 3,520*10(9) kg CO2-eq by 2050 due to animal population growth driven by
      increased demands for meat and dairy products in the world. 

PMID- 25049994
TI  - Effects of substrate to inoculum ratio on the biochemical methane potential of
      piggery slaughterhouse wastes.
AB  - The aim of this study was to assess the effect of substrate to inoculum ratio
      (S/I ratio) on the biochemical methane potential (BMP) and anaerobic
      biodegradability (Ddeg) of different piggery slaughterhouse wastes, such as
      piggery blood, intestine residue, and digestive tract content. These wastes were
      sampled from a piggery slaughterhouse located in Kimje, South Korea. Cumulative
      methane production curves for the wastes were obtained from the anaerobic batch
      fermentation having different S/I ratios of 0.1, 0.5, 1.0, and 1.5. BMP and
      anaerobic biodegradabilities (Ddeg) of the wastes were calculated from cumulative
      methane production data for the tested conditions. At the lowest S/I ration of
      0.1, BMPs of piggery blood, intestine residue, and digestive tract content were
      determined to be 0.799, 0.848, and 1.076 Nm(3) kg(-1)-VSadded, respectively,
      which were above the theoretical methane potentials of 0.539, 0.644, and 0.517
      Nm(3) kg(-1)-VSadded for blood, intestine residue, and digestive tract content,
      respectively. However, BMPs obtained from the higher S/I ratios of 0.5, 1.0, and
      1.5 were within the theoretical range for all three types of waste and were not
      significantly different for the different S/I ratios tested. Anaerobic
      biodegradabilities calculated from BMP data showed a similar tendency. These
      results imply that, for BMP assay in an anaerobic reactor, the S/I ratio of
      anaerobic reactor should be above 0.1 and the inoculum should be sufficiently
      stabilized to avoid further degradation during the assay. 

PMID- 25049995
TI  - Effects of variants in proopiomelanocortin and neuropeptide y genes on growth,
      carcass, and meat quality traits in rabbits.
AB  - Appetite-related neuropeptides proopiomelanocortin (POMC) and Neuropeptide Y
      (NPY) are essential for regulating feeding behavior and energy homeostasis. The
      objective of this study was to evaluate the effects of variants in POMC and NPY
      genes on growth, carcass and meat quality traits in rabbits. A total of six SNPs
      were identified for POMC (n = 2) and NPY (n = 4) genes by direct sequencing.
      Three SNPs were subsequently genotyped by using MassArray system (Sequenom
      iPLEXassay) in 235 individuals, which belong to three meat rabbit breeds,
      including 93 Ira rabbits; 81 Champagne rabbits and 61 Tianfu black rabbits. The
      SNP c.112-12G>T was in intron-exon boundaries (intron 1) of POMC gene, and the
      association analysis showed that individuals with TT genotype had a greater 84 d
      body weight (BW84), eviscerated weight and semi-eviscerated weight than those
      with GT genotype (p<0.05); the TT individuals were also higher than those GG in
      the ripe meat ratio (RMR) (p<0.05). The g.1778G>C SNP, which was in complete
      linkage with other three SNPs (g.1491G>A, g.1525G>T and g.1530C>T) in intron 1 of
      NPY gene, was significantly correlated with eviscerated slaughter percentage and
      semi-eviscerated slaughter percentage in rabbits, and the individuals with CC
      genotype had a better performance than CG genotype (p<0.05). These findings would
      provide primary clues for the biological roles of POMC and NPY underlying the
      rabbit growth-related traits. 

PMID- 25049996
TI  - Empirical Selection of Informative Microsatellite Markers within Co-ancestry Pig
      Populations Is Required for Improving the Individual Assignment Efficiency.
AB  - The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is
      distantly related to Asian and European pig breeds. It has been inbred to
      generate two breeds and crossed with Landrace and Duroc to produce two hybrids
      for laboratory use. Selecting sets of informative genetic markers to track the
      genetic qualities of laboratory animals and stud stock is an important function
      of genetic databases. For more than two decades, Lanyu derived breeds of common
      ancestry and crossbreeds have been used to examine the effectiveness of genetic
      marker selection and optimal approaches for individual assignment. In this paper,
      these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire,
      Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation
      Station Black pig are studied to build a genetic reference database. Nineteen
      microsatellite markers (loci) provide information on genetic variation and
      differentiation among studied breeds. High differentiation index (FST) and
      Cavalli-Sforza chord distances give genetic differentiation among breeds,
      including Lanyu's inbred populations. Inbreeding values (FIS) show that Lanyu and
      its derived inbred breeds have significant loss of heterozygosity. Individual
      assignment testing of 352 animals was done with different numbers of
      microsatellite markers in this study. The testing assigned 99% of the animals
      successfully into their correct reference populations based on 9 to 14 markers
      ranking D-scores, allelic number, expected heterozygosity (HE) or FST,
      respectively. All miss-assigned individuals came from close lineage Lanyu breeds.
      To improve individual assignment among close lineage breeds, microsatellite
      markers selected from Lanyu populations with high polymorphic, heterozygosity,
      FST and D-scores were used. Only 6 to 8 markers ranking HE, FST or allelic number
      were required to obtain 99% assignment accuracy. This result suggests empirical
      examination of assignment-error rates is required if discernible levels of co
      ancestry exist. In the reference group, optimum assignment accuracy was
      achievable achieved through a combination of different markers by ranking the
      heterozygosity, FST and allelic number of close lineage populations. 

PMID- 25049997
TI  - Prolificacy and Its Relationship with Age, Body Weight, Parity, Previous Litter
      Size and Body Linear Type Traits in Meat-type Goats.
AB  - Data on age and body weight at breeding, parity, previous litter size, days open
      and some descriptive body linear traits from 389 meat-type, prolific Black Bengal
      goats in Tripura State of India, were collected for 3 and 1/2 years (2007 to
      2010) and analyzed using logistic regression model. The objectives of the study
      were i) to evaluate the effect of age and body weight at breeding, parity,
      previous litter size and days open on litter size of does; and ii) to investigate
      if body linear type traits influenced litter size in meat-type, prolific goats.
      The incidence of 68.39% multiple births with a prolificacy rate of 175.07% was
      recorded. Higher age (>2.69 year), higher parity order (>2.31), more body weight
      at breeding (>20.5 kg) and larger previous litter size (>1.65) showed an increase
      likelihood of multiple litter size when compared to single litter size. There was
      a strong, positive relationship between litter size and various body linear type
      traits like neck length (>22.78 cm), body length (>54.86 cm), withers height
      (>48.85 cm), croup height (>50.67 cm), distance between tuber coxae bones (>11.38
      cm) and distance between tuber ischii bones (>4.56 cm) for discriminating the
      goats bearing multiple fetuses from those bearing a single fetus. 

PMID- 25049998
TI  - Rapamycin rescues the poor developmental capacity of aged porcine oocytes.
AB  - Unfertilized oocytes age inevitably after ovulation, which limits their
      fertilizable life span and embryonic development. Rapamycin affects mammalian
      target of rapamycin (mTOR) expression and cytoskeleton reorganization during
      oocyte meiotic maturation. The goal of this study was to examine the effects of
      rapamycin treatment on aged porcine oocytes and their in vitro development.
      Rapamycin treatment of aged oocytes for 24 h (68 h in vitro maturation [IVM]; 44
      h+10 MUM rapamycin/24 h, 47.52+/-5.68) or control oocytes (44 h IVM; 42.14+/
      4.40) significantly increased the development rate and total cell number compared
      with untreated aged oocytes (68 h IVM, 22.04+/-5.68) (p<0.05). Rapamycin
      treatment of aged IVM oocytes for 24 h also rescued aberrant spindle organization
      and chromosomal misalignment, blocked the decrease in the level of phosphorylated
      p44/42 mitogen-activated protein kinase (MAPK), and increased the mRNA expression
      of cytoplasmic maturation factor genes (MOS, BMP15, GDF9, and CCNB1) compared
      with untreated, 24 h-aged IVM oocytes (p<0.05). Furthermore, rapamycin treatment
      of aged oocytes decreased reactive oxygen species (ROS) activity and DNA
      fragmentation (p<0.05), and downregulated the mRNA expression of mTOR compared
      with control or untreated aged oocytes. By contrast, rapamycin treatment of aged
      oocytes increased mitochondrial localization (p<0.05) and upregulated the mRNA
      expression of autophagy (BECN1, ATG7, MAP1LC3B, ATG12, GABARAP, and GABARAPL1),
      anti-apoptosis (BCL2L1 and BIRC5; p<0.05), and development (NANOG and SOX2;
      p<0.05) genes, but it did not affect the mRNA expression of pro-apoptosis genes
      (FAS and CASP3) compared with the control. This study demonstrates that rapamycin
      treatment can rescue the poor developmental capacity of aged porcine oocytes. 

PMID- 25049999
TI  - Naturally occurring lactic Acid bacteria isolated from tomato pomace silage.
AB  - Silage making has become a significant method of forage conservation worldwide.
      To determine how tomato pomace (TP) may be used effectively as animal feed, it
      was ensilaged for 90 days and microbiology counts, fermentation characteristics
      and chemical composition of tomato pomace silage (TPS) were evaluated at the
      30th, 60th, and 90th days, respectively. In addition, 103 lactic acid bacteria
      were isolated from TPS. Based on the phenotypic and chemotaxonomic
      characteristics, 16S rDNA sequence and carbohydrate fermentation tests, the
      isolates were identified as 17 species namely: Lactobacillus coryniformis subsp.
      torquens (0.97%), Lactobacillus pontis (0.97%), Lactobacillus hilgardii (0.97%),
      Lactobacillus pantheris (0.97%), Lactobacillus amylovorus (1.9%), Lactobacillus
      panis (1.9%), Lactobacillus vaginalis (1.9%), Lactobacillus rapi (1.9%),
      Lactobacillus buchneri (2.9%), Lactobacillus parafarraginis (2.9%), Lactobacillus
      helveticus (3.9%), Lactobacillus camelliae (3.9%), Lactobacillus fermentum
      (5.8%), Lactobacillus manihotivorans (6.8%), Lactobacillus plantarum (10.7%),
      Lactobacillus harbinensis (16.5%) and Lactobacillus paracasei subsp. paracasei
      (35.0%). This study has shown that TP can be well preserved for 90 days by
      ensilaging and that TPS is not only rich in essential nutrients, but that
      physiological and biochemical properties of the isolates could provide a platform
      for future design of lactic acid bacteria (LAB) inoculants aimed at improving the
      fermentation quality of silage. 

PMID- 25050000
TI  - Nitrogen metabolism in lactating goats fed with diets containing different
      protein sources.
AB  - This study aimed to evaluate urea excretion, nitrogen balance and microbial
      protein synthesis in lactating goats fed with diets containing different protein
      sources in the concentrate (soybean meal, cottonseed meal, aerial part of cassava
      hay and leucaena hay). Four Alpine goats whose mean body weight was 42.6+/-6.1 kg
      at the beginning of the experiment, a mean lactation period of 94.0+/-9.0 days
      and a production of 1.7+/-0.4 kg of milk were distributed in a 4*4 Latin square
      with four periods of 15 days. Diets were formulated to be isonitrogenous,
      containing 103.0 g/kg of CP, 400 g/kg of Tifton 85 hay and 600 g/kg of
      concentrate. Diet containing cottonseed meal provided (p<0.05) increased
      excretion of urea and urea nitrogen in the urine (g/d and mg/kg of BW) when
      compared with leucaena hay. The diets affected the concentrations of urea
      nitrogen in plasma (p<0.05) and excretion of urea nitrogen in milk, being that
      soybean meal and cottonseed meal showed (p<0.05) higher than the average aerial
      part of the cassava hay. The use of diets with cottonseed meal as protein source
      in the concentrate in feeding of lactating goats provides greater nitrogen
      excretion in urine and negative nitrogen balance, while the concentrate with
      leucaena hay as a source of protein, provides greater ruminal microbial protein
      synthesis. 

PMID- 25050001
TI  - Effects of forage sources on rumen fermentation characteristics, performance, and
      microbial protein synthesis in midlactation cows.
AB  - Eight multiparous Holstein cows (632+/-12 kg BW; 135+/-16 DIM) were used in a
      replicated 4*4 Latin square design to evaluate the effects of forage sources on
      rumen fermentation characteristics, performance, and microbial protein (MCP)
      synthesis. The forage portion of the diets contained alfalfa hay (AH), oat hay
      (OH), Leymus chinensis (LC), or rice straw (RS) as the primary source of fiber.
      Diets were isonitrogenous and isocaloric, and cows were fed four corn silages
      based total mixed rations with equivalent nonfiber carbohydrate (NFC) and forage
      neutral detergent fiber (NDF). Dry matter intake was not affected by the source
      of dietary forages, ranging from 18.83 to 19.20 kg/d, consequently, milk yield
      was similar among diets. Because of the numerical differences in milk fat and
      milk protein concentrations, 4% FCM and ECM yields were unchanged (p>0.05). Mean
      rumen pH, NH3-N content, and concentrations of volatile fatty acids in the rumen
      fluid were not affected by the treatments (p>0.05). Dietary treatments did not
      affect the total tract apparent digestibility of dry matter, organic matter, and
      crude protein (p>0.05); however, digestibility of NDF and acid detergent fiber in
      RS diet was higher compared with AH, OH, and LC diets (p<0.05). Total purine
      derivative excretion was higher in cows fed AH, OH, and LC diets compared with
      those fed RS diet (p<0.05), consequently, estimated MCP synthesis was 124.35 g/d
      higher in cows fed AH diet compared with those fed RS diet (p<0.05). The results
      indicated that cows fed AH, OH, LC, and RS diets with an equivalent forage NDF
      and NFC have no unfavourable effect on the ruminal fermentation and productive
      parameters. 

PMID- 25050002
TI  - The Effects of Fat-soluble Vitamin Administration on Plasma Vitamin Status of
      Nursing Pigs Differ When Provided by Oral Administration or Injection.
AB  - Four experiments were conducted to investigate the effect of fat-soluble vitamin
      administration to sows or newborn pigs on plasma vitamin status. In Exp. 1 and 2,
      a total of 24 and 43 newborn pigs were allotted to control and vitamin treatments
      (vitamin D3 with variable addition of vitamins A and E) orally or by i.m.
      injection. In Exp. 3, pigs from Exp. 2 were allotted to 2 treatments (+/-vitamins
      D3 and E in drinking water) for 14 d postweaning. In Exp. 4, twenty-four
      gestating sows were used for 2 treatments (+/-injection of a vitamin D3/A/E
      product 2 wk prepartum). In Exp. 1 and 2, when vitamin D3 was administrated
      orally or by i.m. injection on d 1 of age, pigs had increased plasma 25
      hydroxycholecalciferol (25-OH D3) concentration 10 d after administration
      compared with control pigs (p<0.05). The injectable administration with vitamin
      D3 and E was able to achieve higher plasma 25-OH D3 (p<0.05) and alpha-tocopherol
      (p<0.05) concentrations than oral administration. At weaning, the pigs in the
      injection group had higher plasma 25-OH D3 concentration than those in the other
      groups in both studies (p<0.05). In Exp. 3, water supplementation of vitamin D3
      and E postweaning increased plasma 25-OH D3 and alpha-tocopherol concentrations
      at d 14 postweaning (p<0.01). In Exp. 4, when sows were injected with the vitamin
      D3 product prepartum, serum 25-OH D3 concentrations of sows at farrowing
      (p<0.01), and in their progeny at birth (p<0.01) and weaning (p<0.05) were
      increased. These results demonstrated that fat-soluble vitamin administration to
      newborn pigs increased plasma 25-OH D3 concentration regardless of administration
      routes and alpha-tocopherol concentration by the injectable route, and that water
      supplementation of vitamin D3 and E to nursery pigs increased plasma 25-OH D3 and
      alpha-tocopherol concentrations. Additionally, injecting sows with vitamin D3
      prepartum increased 25-OH D3 in sows and their offspring. If continued research
      demonstrates that the serum levels of 25-OH D3 are critical in weanling pigs, a
      variety of means to increase those levels are available to swine producers. 

PMID- 25050003
TI  - Pig Feeding under the Potato-green Forage Base System with or without Addition of
      Herbs versus a Concentrate Based System: Effect on Post-slaughter Performance and
      Pork Characteristics.
AB  - This study examined carcass and meat quality parameters in growing/finishing pigs
      fed unconventionally versus the concentrate-based system. Ninety-six, 12 wk old
      pigs (34+/-SD 0.3 kg) were randomly divided into three groups, assigned to one of
      the three dietary treatments: standard complete concentrate mixture, conventional
      (C diet); unconventional, steamed potato-green forage-concentrate based diet (U
      diet), and unconventional basal diet+herbage mix (UH diet). Pigs fed U diet
      showed lower dressing percentage, meatiness, loin eye area, and weight of pork
      neck (p<=0.05), but their carcasses were significantly (p<=0.05) longer and had
      increased backfat depth (p<=0.05). There was no impact of the diet on the meat
      content of dry matter, crude ash, acidity, and colour parameters of m.
      longissimus. Unconventional feeding significantly (p<=0.05) elevated water the
      holding capacity of m. longissimus and slightly improved the sensory attributes
      analysis of meat. The addition of herbs resulted in increased loin eye area
      (p<=0.05), decreased fat content (p<=0.05) in m. longissimus, and tended to
      improve some sensory attributes of meat. There were significant gender
      differences in response to all diets. There were significant diet*sex
      interactions for some measured variables, but there were no clearly identifiable
      trends with regard to any specific carcass or meat parameters. Feeding
      unconventional diet to pigs may offer better culinary attributes of the meat, and
      improve some technologically important characteristics of pig carcass, but may
      negatively affect some carcass or meat parameters. 

PMID- 25050004
TI  - Effects of Feeding Rate and Water Temperature on Growth and Body Composition of
      Juvenile Korean Rockfish, Sebastes schlegeli (Hilgendorf 1880).
AB  - Three feeding trials were conducted to evaluate the effects of feeding rate and
      water temperature on growth and body composition of juvenile Korean rockfish,
      Sebastes schlegeli rearing at 3 different water temperatures. A total of 270 fish
      (each experiment) individual body weight (BW) averaging 16+/-0.3 g (mean+/-SD)
      were fed a commercial diet for 4 wk at 16 degrees C, 20 degrees C, and 24 degrees
      C. At each temperature, triplicate tanks were assigned to one of 6 feeding rates:
      1.5%, 2.5%, 2.8%, 3.1%, 3.4%, and satiation (3.7% BW/d) at 16 degrees C, 1.9%,
      2.9%, 3.2%, 3.5%, 3.8% and satiation (4.1% BW/d) at 20 degrees C and 1.7%, 2.7%,
      3.0%, 3.3%, 3.6%, and satiation (3.9% BW/d) at 24 degrees C water temperature.
      Weight gains of fish in satiation and 3.4% groups at 16 degrees C, in satiation
      and 3.8% groups at 20 degrees C and in satiation and 3.6% groups at 24 degrees C
      were significantly higher than those of fish in the other treatments (p<0.05). A
      broken line regression analysis of weight gain indicated that optimum feeding
      rates of juvenile Korean rockfish were 3.41% at 16 degrees C, 3.75% at 20 degrees
      C and 3.34% at 24 degrees C water temperature. Results of the present study
      indicate that the optimum feeding rate could be >3.1% but <3.41% at 16 degrees C,
      >3.5% but <3.75% at 20 degrees C and >3.0% but <3.34% at 24 degrees C. As we
      expected results suggest that fish performed better at 20 degrees C than 16
      degrees C or 24 degrees C water temperature and the optimum feeding rate could be
      3.1% BW/d to 3.7% BW/d in 16 g of juvenile Korean rockfish. 

PMID- 25050005
TI  - Effect of beta-Mannanase and alpha-Galactosidase Supplementation to Soybean Meal
      Based Diets on Growth, Feed Efficiency and Nutrient Digestibility of Rainbow
      Trout, Oncorhynchus mykiss (Walbaum).
AB  - A 12-week feeding trial was conducted with 87 g rainbow trout to evaluate the
      effects on growth performances, feed efficiency and nutrient digestibility of
      adding beta-mannanase and alpha-galactosidase enzymes, solely or in combination.
      Seven diets were prepared by adding beta-mannanase, alpha-galactosidase and mixed
      enzyme at two different levels (1 g/kg and 2 g/kg) to control diet (without
      enzyme) including soybean meal. Mixed enzymes (1 g/kg, 2 g/kg) were prepared by
      adding beta-mannanase and alpha-galactosidase at the same doses (0.5+0.5 g/kg and
      1+1 g/kg). At the end of the experiment, addition of beta-mannanase, alpha
      galactosidase and mixed enzyme to diet containing 44% soybean meal had no
      significant effects on growth performance and gain:feed (p>0.05). In addition,
      adding beta-mannanase, alpha-galactosidase and mixed enzyme in different rations
      to trout diets had no affect on nutrient digestibility and body composition
      (p>0.05). 

PMID- 25050006
TI  - Energy and ileal digestible amino Acid concentrations for growing pigs and
      performance of weanling pigs fed fermented or conventional soybean meal.
AB  - A new strategy of co-inoculating Bacillus subtilis MA139 with Streptococcus
      thermophilus and Saccharomyces cerevisiae was used to produce fermented soybean
      meal (FSBM). Three experiments were conducted to determine the concentration of
      digestible energy (DE) and metabolizable energy (ME) (Exp. 1), apparent ileal
      digestibility (AID) and standardized ileal digestibility (SID) of amino acids
      (AA) (Exp. 2), and feeding value (Exp. 3) of FSBM produced by this new strategy
      (NFSB) compared with soybean meal (SBM) and conventionally available FSBM
      (Suprotein). In Exp. 1, twenty-four barrows (initial body weight [BW] of 32.2 +/
      1.7 kg) were randomly allotted to 1 of 4 diets with 6 replicates per diet. A corn
      basal diet and 3 diets based on a mixture of corn and 1 of 3 soybean products
      listed above were formulated and the DE and ME contents were determined by the
      difference method. The results showed that there were no differences in DE and ME
      between SBM and either FSBM product (p>0.05). In Exp. 2, eight barrows (initial
      BW of 26.8+/-1.5 kg) were fitted with ileal T-cannulaes and used in a replicated
      4*4 Latin square design. Three corn-starch-based diets were formulated using each
      of the 3 soybean products as the sole source of AA. A nitrogen-free diet was also
      formulated to measure endogenous losses of AA. The results showed that the SID of
      all AA except arginine and histidine was similar for NFSB and SBM (p>0.05), but
      Suprotein had greater (p<0.05) SID of most AA except lysine, aspartate, glycine
      and proline than NFSB. In Exp. 3, a total of 144 piglets (initial BW of 8.8+/-1.2
      kg) were blocked by weight and fed 1 of 4 diets including a control diet with 24%
      SBM as well as diets containing 6% and 12% NFSB or 12% Suprotein added at the
      expense of SBM. During d 15 to 28, replacing SBM with 6% NFSB significantly
      improved average daily gain (ADG) and average daily feed intake (ADFI) (p<0.05)
      for nursery piglets. During the overall experiment, ADG of piglets fed diets
      containing 6% NFSB was significantly greater (p<0.05) than that of piglets fed
      SBM. In conclusion, fermentation with the new strategy did not affect the energy
      content or the AID and the SID of AA in SBM. However, inclusion of 6% NFSB in
      diets fed to nursery piglets improved performance after weaning likely as a
      result of better nutritional status and reduced immunological challenge. 

PMID- 25050007
TI  - Bruising in slaughter cattle and its relationship with creatine kinase levels and
      beef quality as affected by animal related factors.
AB  - The objective of the study was to determine the effects of animal related factors
      on bruising in slaughter cattle, creatine kinase (CK) and beef quality. Three
      hundred and twenty one cattle from three breeds (108 Bonsmara, 130 Beefmaster and
      83 Brahman) were used in this study. The animals were grouped as follows: Group 1
      (16 months old), Group 2 (18 months old) and Group 3 (24 months old). At
      exsanguinations, blood samples for CK determination were collected using
      disposable vacutainer tubes. Muscularis longissimus thoracis et lumborum (LTL)
      was collected 24 h after slaughter to determine the colour (L*, a*, and b*) and
      ultimate pH (pHu) of beef. Breed, sex and age had significant effects (p<0.05) on
      bruising score, CK levels and beef quality. Bonsmara breed had the highest (80%)
      bruising score percentage, CK (705.3+/-80.57 U/L) and pHu (6.3+/-0.05) values
      while the Bonsmara had the highest L* (24.8+/-0.78) a* (17.5+/-0.53) and b*
      (12.8+/-0.53) values. Higher CK levels were also observed in winter compared to
      summer, spring and autumn respectively. Therefore, animal factors (sex, breed and
      animal age at slaughter) contribute to the development of bruises and have an
      effect on the levels of CK and meat quality. It was also concluded that there is
      no significant relationship between meat parameters (L,* a*, and b*) and CK
      levels. 

PMID- 25050008
TI  - Effects of housing systems and the diet supplements on the slaughter value and
      concentration of mineral elements in the loin muscle of lambs.
AB  - The objective of this study was to investigate the effect of maintenance system
      as well as the effect of Se, Zn, and vitamin E supplementation of ram-lambs on
      the slaughter value and concentration of mineral elements in the loin muscle of
      lambs. The experiment was conducted on 72 Polish Merino ram-lambs divided into
      three groups: group C, indoor with no supplement, 19 lambs; S, indoor with
      supplement, 23 lambs; G, outdoor with no supplement, 30 lambs. From birth all the
      lambs were maintained indoor with their dams and then weaned at the age of 8
      weeks. The rams from group C and S were placed in individual straw-bedded pens
      and fattened individually with concentrate mixture offered ad libitum until the
      age of 16 weeks. The lambs from group G were grazed every day from May to July (2
      months). During the fattening period each lamb from the supplemented group S was
      administered per os 1 mL 0.1% Na2SeO4 (Se, 0.42 mg), 3 mL 10% ZnSO4 (Zn, 68 mg),
      and 1 mL premix protect vitamin E (0.1 g alpha-tocopherol, 5 mg lysine, 5 mg
      methionine) daily. A comparison of half carcasses across the groups has shown no
      difference between the control group and the one with supplements, while the
      weight of half carcasses in the grazing group was smaller in comparison with
      groups C and S (p<0.001). The meat content in the pelvic limb showed no
      differences across all groups under study. The pelvic limb of grazing lambs
      contained less fat compared to the control and supplemented groups (p<0.001). The
      concentrations of Se and Zn in the blood plasma of ram-lambs from the
      supplemented group were significantly higher than for the control and grazing
      lambs. Inorganic Se and Zn supplementation with vitamin E to the diet of lambs
      increased Se and Zn levels in loin muscle (p<0.001) to 0.46 MUg/g and 32.9 MUg/g
      in fresh tissue, respectively. 

PMID- 25050009
TI  - Effect of Glucagon-like Peptide 2 on Tight Junction in Jejunal Epithelium of
      Weaned Pigs though MAPK Signaling Pathway.
AB  - The glucagon-like peptide 2 (GLP-2) that is expressed in intestine epithelial
      cells of mammals, is important for intestinal barrier function and regulation of
      tight junction (TJ) proteins. However, there is little known about the
      intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets'
      intestinal epithelial cells. The purpose of this study is to test the hypothesis
      that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated
      protein kinase (MAPK) signaling pathway in piglets' intestinal epithelial cells.
      The jejunal tissues were cultured in a Dulbecco's modified Eagle's medium/high
      glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the
      treatment with the appropriate concentrations of GLP-2, the mRNA and protein
      expressions of zonula occludens-1 (ZO-1), occludin and claudin-1 were increased
      (p<0.05). U0126, an MAPK kinase inhibitor, prevented the mRNA and protein
      expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05). In
      conclusion, these results indicated that GLP-2 could improve the expression of TJ
      proteins in weaned pigs' jejunal epithelium, and the underlying mechanism may due
      to the MAPK signaling pathway. 

PMID- 25050010
TI  - Molecular Characterization and Expression Analysis of Equine Vascular Endothelial
      Growth Factor Alpha (VEGFalpha) Gene in Horse (Equus caballus).
AB  - The objective of this study was to determine the molecular characteristics of the
      horse vascular endothelial growth factor alpha gene (VEGFalpha) by constructing a
      phylogenetic tree, and to investigate gene expression profiles in tissues and
      blood leukocytes after exercise for development of suitable biomarkers. Using
      published amino acid sequences of other vertebrate species (human, chimpanzee,
      mouse, rat, cow, pig, chicken and dog), we constructed a phylogenetic tree which
      showed that equine VEGFalpha belonged to the same clade of the pig VEGFalpha.
      Analysis for synonymous (Ks) and non-synonymous substitution ratios (Ka) revealed
      that the horse VEGFalpha underwent positive selection. RNA was extracted from
      blood samples before and after exercise and different tissue samples of three
      horses. Expression analyses using reverse transcription-polymerase chain reaction
      (RT-PCR) and quantitative-polymerase chain reaction (qPCR) showed ubiquitous
      expression of VEGFalpha mRNA in skeletal muscle, kidney, thyroid, lung, appendix,
      colon, spinal cord, and heart tissues. Analysis of differential expression of
      VEGFalpha gene in blood leukocytes after exercise indicated a unimodal pattern.
      These results will be useful in developing biomarkers that can predict the
      recovery capacity of racing horses. 

PMID- 25050011
TI  - Effects of Vitamin C or E on the Pro-inflammatory Cytokines, Heat Shock Protein
      70 and Antioxidant Status in Broiler Chicks under Summer Conditions.
AB  - The present study was carried out to investigate the effects of dietary
      antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and
      antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d
      old broiler chicks were randomly assigned to a basal diet (CON) and the basal
      diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg,
      VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at
      average daily fluctuations of temperature between 32 degrees C to 34 degrees C at
      day to 27 degrees C to 29 degrees C at night for the entire feeding periods.
      There was no significant difference in body weight, feed to gain ratio and the
      relative organ weight except the thymus in response to dietary vitamin C or E
      supplementation. However, the mRNA expression of interleukin (IL)-1beta, IL-6,
      interferon (IFN)-gamma, Toll like receptor (TLR)-4 and HSP70 in the liver of
      birds fed diet containing vitamin C significantly (p<0.05) decreased compared
      with those in birds fed basal diet. Dietary vitamin E also showed a significant
      (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal
      diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented
      diet was significantly (p<0.05) higher with than that in birds a basal diet.
      Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease
      in response to dietary vitamin C or E supplementation. In conclusion, dietary
      supplementation with antioxidant vitamins, especially vitamin C resulted in a
      significant decrease in the mRNA expression of pro-inflammatory cytokines and
      HSP70, and higher antioxidant parameters than that of birds on the basal diet
      under summer conditions. 

PMID- 25050012
TI  - Historical Overview of the Effect of beta-Adrenergic Agonists on Beef Cattle
      Production.
AB  - Postnatal muscle hypertrophy of beef cattle is the result of enhanced
      myofibrillar protein synthesis and reduced protein turnover. Skeletal muscle
      hypertrophy has been studied in cattle fed beta-adrenergic agonists (beta-AA),
      which are receptor-mediated enhancers of protein synthesis and inhibitors of
      protein degradation. Feeding beta-AA to beef cattle increases longissimus muscle
      cross-sectional area 6% to 40% compared to non-treated cattle. The beta-AA have
      been reported to improve live animal performance, including average daily gain,
      feed efficiency, hot carcass weight, and dressing percentage. Treatment with beta
      AA increased mRNA concentration of the beta 2 or beta 1-adrenergic receptor and
      myosin heavy chain IIX in bovine skeletal muscle tissue. This review will examine
      the effects of skeletal muscle and adipose development with beta-AA, and will
      interpret how the use of beta-AA affects performance, body composition, and
      growth in beef cattle. 

PMID- 25050013
TI  - Towards conservation of omani local chicken: phenotypic characteristics,
      management practices and performance traits.
AB  - Characterizing local chicken types and their mostly rural production systems is
      prerequisite for designing and implementing development and conservation
      programs. This study evaluated the management practices of small-scale chicken
      keepers and the phenotypic and production traits of their chickens in Oman, where
      conservation programs for local livestock breeds have currently started. Free
      range scavenging was the dominant production system, and logistic regression
      analysis showed that socio-economic factors such as training in poultry keeping,
      household income, income from farming and gender of chicken owners influenced
      feeding, housing, and health care practices (p<0.05). A large variation in
      plumage and shank colors, comb types and other phenotypic traits within and
      between Omani chicken populations were observed. Male and female body weight
      differed (p<0.05), being 1.3+/-0.65 kg and 1.1+/-0.86 kg respectively. Flock size
      averaged 22+/-7.7 birds per household with 4.8 hens per cock. Clutch size was
      12.3+/-2.85 and annual production 64.5+/-2.85 eggs per hen. Egg hatchability
      averaged 88+/-6.0% and annual chicken mortality across all age and sex categories
      was 16+/-1.4%. The strong involvement of women in chicken keeping makes them key
      stakeholders in future development and conservation programs, but the latter
      should be preceded by a comprehensive study of the genetic diversity of the Omani
      chicken populations. 

PMID- 25050015
TI  - Factor analysis of linear type traits and their relation with longevity in
      brazilian holstein cattle.
AB  - In this study we aimed to evaluate the reduction in dimensionality of 20 linear
      type traits and more final score in 14,943 Holstein cows in Brazil using factor
      analysis, and indicate their relationship with longevity and 305 d first
      lactation milk production. Low partial correlations (-0.19 to 0.38), the medium
      to high Kaiser sampling mean (0.79) and the significance of the Bartlett
      sphericity test (p<0.001), indicated correlations between type traits and the
      suitability of these data for a factor analysis, after the elimination of seven
      traits. Two factors had autovalues greater than one. The first included width and
      height of posterior udder, udder texture, udder cleft, loin strength, bone
      quality and final score. The second included stature, top line, chest width, body
      depth, fore udder attachment, angularity and final score. The linear regression
      of the factors on several measures of longevity and 305 d milk production showed
      that selection considering only the first factor should lead to improvements in
      longevity and 305 milk production. 

PMID- 25050014
TI  - Mutations of TYR and MITF Genes are Associated with Plumage Colour Phenotypes in
      Geese.
AB  - The polymorphism of microphthalmia-associated transcription factor (MITF) and
      tyrosinase (TYR) genes have been proposed to play a vital role in coat colour
      genesis in mammals, but their role remains ambiguous in geese at best. Here, we
      cloned and sequenced 1,397 bp coding region of MITF gene and a 588 bp fragment of
      TYR exon 1 for polymorphism analysis among 157 domestic geese showing three types
      of plumage colour. We detected a total of three SNPs (c.280T>C, c.345G>A, and
      c.369G>A) in TYR and six haplotypes (H1-H6). Among them, haplotypes H1, H2, H3,
      and H5 were significantly associated with white plumage trait of Zhedong White
      Geese. However, only diplotype H1H1 and H3H5 were significantly associated with
      white plumage trait of Zhedong White Geese (p<0.01). We only detected one SNP
      (c.1109C>T) for MITF gene and found that genotype CT and TT were significantly
      associated with white plumage trait of Zhedong White Geese. Briefly, our study
      suggested an association between polymorphisms of TYR and MITF genes and the
      plumage colour trait in domestic geese. 

PMID- 25050017
TI  - Effect of Crude Protein Levels in Concentrate and Concentrate Levels in Diet on
      In vitro Fermentation.
AB  - The effect of concentrate mixtures with crude protein (CP) levels 10%, 13%, 16%,
      and 19% and diets with roughage to concentrate ratios 80:20, 60:40, 40:60, and
      20:80 (w/w) were determined on dry matter (DM) and organic matter (OM)
      digestibility, and fermentation metabolites using an in vitro fermentation
      technique. In vitro fermented attributes were measured after 4, 24, and 48 h of
      incubation respectively. The digestibility of DM and OM, and total volatile fatty
      acid (VFA) increased whereas pH decreased with the increased amount of
      concentrate in the diet (p<0.001), however CP levels of concentrate did not have
      any influence on these attributes. Gas production reduced with increased CP
      levels, while it increased with increasing concentrate levels. Ammonia nitrogen
      (NH3-N) concentration and microbial CP production increased significantly
      (p<0.05) by increasing CP levels and with increasing concentrate levels in diet
      as well, however, no significant difference was found between 16% and 19% CP
      levels. Therefore, 16% CP in concentrate and increasing proportion of concentrate
      up to 80% in diet all had improved digestibility of DM and organic matter, and
      higher microbial protein production, with improved fermentation characteristics. 

PMID- 25050016
TI  - L-carnitine Supplemented Extender Improves Cryopreserved-thawed Cat Epididymal
      Sperm Motility.
AB  - Cryopreservation of epididymal sperm is an effective technique to preserve
      genetic materials of domestic cats and wild felids when they unexpectedly die.
      However, this technique inevitably causes detrimental changes of cryopreserved
      thawed spermatozoa, for example, by physical damage and excessive oxidative
      stress. L-carnitine is an antioxidant that has been used to improve sperm
      motility in humans and domestic animals. This study aimed to investigate the
      effects of L-carnitine on cat epididymal sperm quality following cryopreservation
      and thawing. After routine castration, cauda epididymides were collected from 60
      cat testes. The epididymal spermatozoa from 3 cauda epididymides were pooled as 1
      replicate. Spermatozoa samples (16 replicates) were examined for spermatozoa
      quality and then randomly divided into 4 groups: 0 mM L-carnitine (control), 12.5
      mM, 25 mM and 50 mM L-carnitine. The sperm aliquots were then equilibrated and
      conventionally frozen. After thawing, sperm motility, plasma membrane integrity,
      DNA integrity and acrosome integrity were evaluated. The 25 mM L-carnitine
      significantly improved sperm motility compared with a control group (p<0.05),
      although this was not significantly different among other concentrations. In
      conclusion, supplementation of 25 mM L-carnitine in freezing extender improves
      cauda epididymal spermatozoa motility. The effects of L-carnitine on the levels
      of oxidative stress during freezing and thawing remains to be examined. 

PMID- 25050018
TI  - Levels of supplementation for grazing beef heifers.
AB  - The objective of this experiment was to evaluate the effect of providing
      different levels of a supplement on the nutritional characteristics and
      productive performance of heifers on pasture during the rainy-dry transition and
      dry season in Brazil or tropical area. Thirty crossbred heifers with predominance
      of Zebu breed were used in a completely randomized experimental design.
      Treatments consisted of a mineral supplement and 0.5, 1.0, 1.5, or 2.0
      kg/animal/d of a protein supplement containing 300 g crude protein (CP)/kg of dry
      matter (DM). In the rainy-dry transition season there was quadratic effect of the
      protein supplementation (p<0.10) on daily weight gain (DWG). A linear
      relationship (p<0.10) was found between increasing supplement intake and intakes
      of DM, organic matter (OM), crude protein (CP), ether extract (EE), non fibrous
      carbohydrates (NFC) and total digestible nutrients (TDN). Coefficients of
      apparent digestibility of CP, EE, and NFC increased linearly (p<0.10) with
      increasing supplement levels, but there was no effect on the DM apparent
      digestibility (p>0.10); the microbial efficiency (g CPmic/kg TDN) and the
      relationship of microbial nitrogen flow with nitrogen intake (g/g nitrogen
      intake) were negative linear profiles. In the dry season, the descriptive pattern
      least squares means showed a trend of stabilization of DWG from the supply of
      0.98 kg of protein supplement; the intakes of DM, OM, CP, EE, NFC, and TDN showed
      increasing linear relationship (p<0.10) with protein supplement levels; the means
      of apparent digestibility coefficients of the different dietary fractions
      presented a linear-response-plateau (LRP); the microbial nitrogen flow (g/d)
      showed positive linear profile (p<0.10) for supplementation levels. It is
      concluded that supplementation improves the productive performance of grazing
      heifers and that 1.0 kg/d of supplement per animal gives the maximum increment of
      weight gain. 

PMID- 25050019
TI  - Seasonal Variations in Voluntary Intake and Apparent Digestibility of Forages in
      Goats Grazing on Introduced Leymus chinensis Pasture.
AB  - The nutrient composition of pasture, voluntary intake and digestibility of diet
      ingested by goats grazing on an introduced Leymus chinensis pasture were measured
      across spring (May), summer (July), autumn (October) and winter (March). In each
      season, 12 Inner Mongolian Cashmere goats (6 wethers and 6 does with an average
      live weight of 22.2+/-1.3 kg and 19.5+/-0.8 kg, respectively) were used to graze
      on a 2 hectares size paddock. Diet selection was observed and the plant parts
      selected by grazing goats and whole plant L. chinensis were sampled
      simultaneously. The alkane pair C32:C33 and C36 were used to estimate intake and
      digestibility, respectively. The results showed that the plant parts selected by
      goats had higher crude protein (CP) and lower acid detergent fiber (ADF) and
      neutral detergent fiber (NDF) than the whole plant, especially in the autumn and
      winter. The voluntary intake of dry matter (DM), CP, ADF, NDF, and metabolizable
      energy (ME) by goats was highest in summer (p<0.05). The goats ingested more CP,
      ME, and less ADF in spring than in autumn (p<0.05). The intakes of DM, CP, and ME
      were lowest in winter (p<0.05). There were significant differences in nutrient
      intake between wethers and does in each season, except for the ADF and ME intake
      per metabolic weight (LW(0.75)). The nutrient digestibilities were higher in
      spring and summer, and decreased significantly during the autumn and winter
      (p<0.05). Goats, especially wethers, had a relative constant NDF digestibility
      across seasons, however, the apparent digestibility of CP in both wethers and
      does, decreased to negative values in winter. The grazing goats experienced
      relatively sufficient nutrients supply in spring and summer, and a severe
      deficiency of CP and ME in winter. 

PMID- 25050020
TI  - Determination of Nutrient Contents and In vitro Gas Production Values of Some
      Legume Forages Grown in the Harran Plain Saline Soils.
AB  - The aim of this study was to determine the nutritive value of some legume species
      in salt-affected soils of South-East Anatolian region using chemical composition
      and in vitro gas production kinetics. In this study, Lotus corniculatus,
      Trifolium alexandrinum, Medicago sativa were sown and tested in four different
      locations. A 3 by 4 factorial design with 3 legume species and 4 salt levels (non
      salty electrical conductivity (EC)<4 dS/m; low salt: 4 dS/m>EC<8 dS/m, medium
      saline: 8 dS/m>EC<16 dS/m and high salt: 16 dS/m>EC) was used in the study.
      Results indicated that salinity and plants had no significant effect on ash and
      ether extract. Dry matter (DM), acid detergent fiber, digestible dry matter, dry
      matter intake (DMI) were affected by plant, salinity and plant*salinity
      interaction. On the other hand neutral detergent fiber, relative feed value
      (RFV), and DMI were affected by salinity and plant*salinity interaction. Mineral
      contents were affected by plant species, salinity and salinity*plants
      interactions. In vitro gas production, their kinetics and estimated parameters
      such as were not affected by salinity whereas the gas production up to 48 h,
      organic matter digestibility, metabolizable energy (ME), and net energy lactation
      (NEL) were affected by plant and plant*salt interaction. Generally RFVs of all
      species ranged from 120 to 210 and were quite satisfactory in salty conditions.
      Current results show that the feed value of Medicago sativa is higher compared to
      Lotus corniculatus and Trifolium alexandrinum. 

PMID- 25050021
TI  - Effects of Storage Duration and Temperature on the Chemical Composition,
      Microorganism Density, and In vitro Rumen Fermentation of Wet Brewers Grains.
AB  - This study aimed to investigate the effects of storage duration and temperature
      on the characteristics of wet brewers grains (WBG) as feeds for ruminant animals.
      Four storage temperatures (5 degrees C, 15 degrees C, 25 degrees C, and 35
      degrees C) and four durations (0, 1, 2, and 3 d) were arranged in a 4*4 factorial
      design. Surface spoilage, chemical composition and microorganism density were
      analyzed. An in vitro gas test was also conducted to determine the pH, ammonia
      nitrogen and volatile fatty acid (VFA) concentrations after 24 h incubation.
      Surface spoilage was apparent at higher temperatures such as 25 degrees C and 35
      degrees C. Nutrients contents decreased concomitantly with prolonged storage
      times (p<0.01) and increasing temperatures (p<0.01). The amount of yeast and mold
      increased (p<0.05) with increasing storage times and temperatures. As storage
      temperature increased, gas production, in vitro disappearance of organic matter,
      pH, ammonia nitrogen and total VFA from the WBG in the rumen decreased (p<0.01).
      Our results indicate that lower storage temperature promotes longer beneficial
      use period. However, when storage temperature exceeds 35 degrees C, WBG should be
      used within a day to prevent impairment of rumen fermentation in the subtropics
      such as Southeast China, where the temperature is typically above 35 degrees C
      during summer. 

PMID- 25050022
TI  - Effect of Two-step Time-restricted Feeding on the Fattening Traits in Geese.
AB  - The present study was conducted to determine whether the two-step time-restricted
      feeding improves the fattening traits of one-step time-restricted feeding in
      geese. Thirty-six 8-wk-old geese were allotted into one of three groups. Group R1
      (the 1-step restricted feeding group) was allowed access to feed for 2 h in the
      morning from 8 wk to 14 wk of age. Group R2 (the 2-step restricted feeding group)
      was treated as Group R1, but was additionally fed for 2 h in the afternoon from
      12 wk to 14 wk of age. Group C (the control group) was fed ad libitum from 8 wk
      to 14 wk of age. Feed intake and body weight (BW) were recorded daily and weekly,
      respectively. At 14 wk of age, the blood samples were collected to determine the
      fasting plasma levels of glucose, triacylglycerols and uric acid before
      sacrifice. The results showed that daily feed intake (DFI) was lower, feed
      efficiency (FE) was higher in both Groups R1 and R2 than in Group C, and daily
      gain (DG) in Group R2 was higher than in Group R1 during the whole experimental
      period (p<0.05). Group R1 exhibited lower abdominal and visceral fat weights in
      carcass than did Group C (p<0.05), and Group R2 was in intermediate. The fasting
      plasma glucose levels in Group C were higher, and triacylglycerol levels in Group
      R1 were higher, compared with the other groups (p<0.05). It is concluded that
      time-restricted feeding in the fattening period not only increases FE but reduces
      DFI, and the additional meal during the late fattening period improves the DG
      without the expense of FE in geese. 

PMID- 25050023
TI  - Effects of black pepper (piper nigrum), turmeric powder (curcuma longa) and
      coriander seeds (coriandrum sativum) and their combinations as feed additives on
      growth performance, carcass traits, some blood parameters and humoral immune
      response of broiler chickens.
AB  - Different herbs and spices have been used as feed additives for various purposes
      in poultry production. This study was conducted to assess the effect of feed
      supplemented with black pepper (Piper nigrum), turmeric powder (Curcuma longa),
      coriander seeds (Coriandrum sativum) and their combinations on the performance of
      broilers. A total of 210 (Cobb) one-d-old chicks were divided into seven groups
      of 30 birds each. The treatments were: a control group received no supplement,
      0.5% black pepper (T1), 0.5% turmeric powder (T2), 2% coriander seeds (T3), a
      mixture of 0.5% black pepper and 0.5% turmeric powder (T4), a mixture of 0.5%
      black pepper and 2% coriander seed (T5), and a mixture of 0.5% black pepper, 0.5%
      turmeric powder and 2% coriander seeds (T6). Higher significant values of body
      weight gain during the whole period of 5 weeks (p<0.001) were observed in
      broilers on T1, T3, T5, and T6 compared to control. Dietary supplements with T1,
      T2, T3, and T6 improved the cumulative G:F of broilers during the whole period of
      5 weeks (p<0.001) compared with control. The dressing percentage and edible
      giblets were not influenced by dietary supplements, while higher values of
      relative weight of the liver (p<0.05) were obtained in T5 and T6 compared to
      control. The addition of feed supplements in T5 and T6 significantly increased
      serum total protein and decreased serum glucose, triglycerides and alkaline
      phosphatase concentrations compared with the control group (p<0.05). Broilers on
      T6 showed significant decrease in the serum glutamate pyruvate transaminase
      concentration (p<0.05) compared to control. The broilers having T5 and T6
      supplemented feed had relatively greater antibody titre (p<0.001) at 35 d of age
      than control. It is concluded that dietary supplements with black pepper or
      coriander seeds or their combinations enhanced the performance and health status
      of broiler chickens. 

PMID- 25050024
TI  - Effects of Xylanase Supplementation on Growth Performance, Nutrient Digestibility
      and Non-starch Polysaccharide Degradation in Different Sections of the
      Gastrointestinal Tract of Broilers Fed Wheat-based Diets.
AB  - This experiment was performed to investigate the effects of exogenous xylanase
      supplementation on performance, nutrient digestibility and the degradation of non
      starch polysaccharides (NSP) in different sections of the gastrointestinal tract
      (GIT) of broilers fed wheat-based diets. A total of 120 7-day-old Arbor Acres
      broiler chicks were randomly allotted to two wheat-based experimental diets
      supplemented with 0 or 1.0 g/kg xylanase. Each treatment was composed of 6
      replicates with 10 birds each. Diets were given to the birds from 7 to 21 days of
      age. The results showed that xylanase supplementation did not affect feed intake,
      but increased body weight gain of broiler at 21 day of age by 5.8% (p<0.05) and
      improved feed-to-gain ratio by 5.0% (p<0.05). Xylanase significantly increased
      (p<0.05) ileal digestibilities of crude protein (CP) by 3.5%, starch by 9.3%,
      soluble NSP by 43.9% and insoluble NSP by 42.2% relative to the control group,
      respectively. Also, compared with the control treatment, xylanase addition
      increased (p<0.05) total tract digestibilities of dry matter by 5.7%, CP by 4.1%,
      starch by 6.3%, soluble NSP by 50.8%, and had a tendency to increase (p = 0.093)
      insoluble NSP by 19.9%, respectively. The addition of xylanase increased the
      concentrations of arabinose and xylose in the digesta of gizzard, duodenum,
      jejunum, and ileum (p<0.05), and the order of their concentration was
      ileum>jejunum>duodenum>>gizzard> caecum. The supplementation of xylanse increased
      ileal isomaltriose concentration (p<0.05), but did not affect the concentrations
      of isomaltose, panose and 1-kestose in the digesta of all GIT sections. These
      results suggest that supplementation of xylanase to wheat-based diets cuts the
      arabinoxylan backbone into small fragments (mainly arabinose and xylose) in the
      ileum, jejunum and duodenum, and enhances digestibilites of nutrients by
      decreasing digesta viscosity. The release of arabinose and xylose in the small
      intestine may also be the important contributors to the growth-promoting effect
      of xylanase in broilers fed wheat-based diets. 

PMID- 25050025
TI  - Effects of dietary fermented seaweed and seaweed fusiforme on growth performance,
      carcass parameters and immunoglobulin concentration in broiler chicks.
AB  - This study was conducted to investigate the effects of brown seaweed (Undaria
      pinnatifida) by-product and seaweed fusiforme (Hizikia fusiformis) by-product
      supplementation on growth performance and blood profiles including serum
      immunoglobulin (Ig) in broilers. Fermentation of seaweeds was conducted by
      Bacillus subtilis and Aspergillus oryzae. In a 5-wk feeding trial, 750 one-d-old
      broiler chicks were divided into 5 groups, and were assigned to the control diet
      or experimental diets including control+0.5% brown seaweed (BS) by-product,
      control+0.5% seaweed fusiforme (SF) by-product, control+0.5% fermented brown
      seaweed (FBS) by-product, and control+0.5% fermented seaweed fusiforme (FSF) by
      product. As a consequence, body weight gain (BWG) and gain:feed of seaweed by
      product groups were clearly higher, when compared to those of control diet group
      from d 18 to 35 and the entire experimental period (p<0.05). In mortality rate,
      seaweed by-product groups were significantly lower when compared to control diet
      group during entire experimental period (p<0.05). However, Feed Intake of
      experimental diets group was not different from that of the control group during
      the entire experimental period. Whereas, Feed Intake of fermented seaweed by
      product groups was lower than that of non-fermented seaweed groups (p<0.05).
      Total organ weights, lipids, and glutamic oxalacetic transaminase (GOT) of all
      treatment groups were not different from those of control group. However,
      glutamic pyruvate transaminase (GPT) of all treatment groups was higher than that
      of control group at d 17 (p<0.05). In case of serum Igs concentration, the
      concentration of IgA antibody in BS, SF, FSF treatment groups was significantly
      higher than in control group at d 35 (p<0.01). IgA concentration in FBS
      supplementation groups was negligibly decreased when compared to the control
      group. IgM concentration in the serums of all treatment groups was significantly
      higher than in control group (p<0.05) and in fermented seaweed by-product groups
      were much higher than in non-fermented seaweed groups (p<0.05). On the other
      hand, IgG concentrations in all treatment groups were lower than in control group
      (p<0.05). Taken together, our results suggest that by-product dietary
      supplementation of BS, SF, FBS, and FSF in poultry may provide positive effects
      of growth performance and immune response. 

PMID- 25050026
TI  - Determination and prediction of digestible and metabolizable energy from the
      chemical composition of chinese corn gluten feed fed to finishing pigs.
AB  - Two experiments were conducted to determine the digestible energy (DE) and
      metabolizable energy (ME) contents of corn gluten feed (CGF) for finishing pigs
      and to develop equations predicting the DE and ME content from the chemical
      composition of the CGF samples, as well as validate the accuracy of the
      prediction equations. In Exp. 1, ten CGF samples from seven provinces of China
      were collected and fed to 66 finishing barrows (Duroc*Landrace*Yorkshire) with an
      initial body weight (BW) of 51.9+/-5.5 kg. The pigs were assigned to 11 diets
      comprising one basal diet and 10 CGF test diets with six pigs fed each diet. The
      basal diet contained corn (76%), dehulled soybean meal (21%) and premix (3%). The
      ten test diets were formulated by substituting 25% of the corn and dehulled
      soybean meal with CGF and contained corn (57%), dehulled soybean meal (15.75%),
      CGF (24.25%) and premix (3%). In Exp. 2, two additional CGF sources were
      collected as validation samples to test the accuracy of the prediction equations.
      In this experiment, 18 barrows (Duroc*Landrace*Yorkshire) with an initial BW of
      61.1+/-4.0 kg were randomly allotted to be fed either the basal diet or two CGF
      containing diets which had a similar composition as used in Exp. 1. The DE and ME
      of CGF ranged from 10.37 to 12.85 MJ/kg of dry matter (DM) and 9.53 to 12.49
      MJ/kg of DM, respectively. Through stepwise regression analysis, several
      prediction equations of DE and ME were generated. The best fit equations were:
      DE, MJ/kg of DM = 18.30-0.13 neutral detergent fiber-0.22 ether extract, with
      R(2) = 0.95, residual standard deviation (RSD) = 0.21 and p<0.01; and ME, MJ/kg
      of DM = 12.82+0.11 Starch-0.26 acid detergent fiber, with R(2) = 0.94, RSD = 0.20
      and p<0.01. These results indicate that the DE and ME content of CGF varied
      substantially but the DE and ME for finishing pigs can be accurately predicted
      from equations based on nutritional analysis. 

PMID- 25050027
TI  - Effect of Free-range Rearing on Meat Composition, Physical Properties and Sensory
      Evaluation in Taiwan Game Hens.
AB  - Experiments were conducted to evaluate the effect of an outdoor-grazed raising
      model on meat composition, physical properties and sensory attributes of Taiwan
      game hens. Six hundred 1-d old female chicks were raised on a floor for 8 weeks.
      On day 57, 600 healthy birds, with similar body weight, were selected and
      randomly assigned to three treatment groups (cage, floor-pen and free-range). The
      results showed that different feeding models had no effect on drip loss, cooking
      loss, moisture, crude protein, crude fat, crude ash, zinc and calorie contents in
      breast meat and moisture content in thigh meat. The free-range group had the
      lowest fat content in both breast and thigh meat, and the lowest calorie content
      in thigh meat. The firmness and toughness in both thigh and breast of the free
      range group were the highest values (p<0.05). The crude protein, total collagen,
      zinc and iron contents in thigh meat and total collagen content in breast meat of
      the free-range group were significantly higher than those of the cage-feeding
      group (p<0.05). The meat sensory scores of flavor, chewiness and overall
      acceptability of both thigh and breast meat of the free-range group were
      significantly (p<0.05) better than those of the other two groups. Moreover, the
      current findings also indicate that the Taiwan game hens of the free-range
      feeding model displayed well-received carcass traits and meat quality, with
      higher scores for flavor, chewiness and overall acceptability for greater sensory
      satisfaction in both breast and thigh meat. In addition, the thigh meat contained
      high protein and total collage but low fat, offering a healthier diet choice. 

PMID- 25050028
TI  - Principal milk components in buffalo, holstein cross, indigenous cattle and red
      chittagong cattle from bangladesh.
AB  - The aim of the present study was to get a total physical and chemical
      characterization and comparison of the principal components in Bangladeshi
      buffalo (B), Holstein cross (HX), Indigenous cattle (IC) and Red Chittagong
      Cattle (RCC) milk. Protein and casein (CN) composition and type, casein micellar
      size (CMS), naturally occurring peptides, free amino acids, fat, milk fat globule
      size (MFGS), fatty acid composition, carbohydrates, total and individual minerals
      were analyzed. These components are related to technological and nutritional
      properties of milk. Consequently, they are important for the dairy industry and
      in the animal feeding and breeding strategies. Considerable variation in most of
      the principal components of milk were observed among the animals. The milk of RCC
      and IC contained higher protein, CN, beta-CN, whey protein, lactose, total
      mineral and P. They were more or less similar in most of the all other
      components. The B milk was found higher in CN number, in the content of alphas2-,
      kappa-CN and alpha-lactalbumin, free amino acids, unsaturated fatty acids, Ca and
      Ca:P. The B milk was also lower in beta-lactoglobulin content and had the largest
      CMS and MFGS. Proportion of CN to whey protein was lower in HX milk and this milk
      was found higher in beta-lactoglobulin and naturally occuring peptides.
      Considering the results obtained including the ratio of alphas1-, alphas2-, beta-
      and kappa-CN, B and RCC milk showed best data both from nutritional and
      technological aspects. 

PMID- 25050029
TI  - Comparison of faecal microbial community of lantang, bama, erhualian, meishan,
      xiaomeishan, duroc, landrace, and yorkshire sows.
AB  - The objective of this study was to investigate differences in the faecal
      microbial composition among Lantang, Bama, Erhualian, Meishan, Xiaomeishan,
      Duroc, Landrace, and Yorkshire sows and to explore the possible link of the pig
      breed with the gut microbial community. Among the sows, the Meishan, Landrace,
      Duroc, and Yorkshire sows were from the same breeding farm with the same feed.
      Fresh faeces were collected from three sows of each purebred breed for microbiota
      analysis and volatile fatty acid (VFA) determination. Denaturing gradient gel
      electrophoresis (DGGE) analysis revealed that samples from Bama, Erhualian, and
      Xiaomeishan sows, which from different farms, were generally grouped in one
      cluster, with similarity higher than 67.2%, and those from Duroc, Landrace, and
      Yorkshire sows were grouped in another cluster. Principal component analysis of
      the DGGE profile showed that samples from the foreign breeds and the samples from
      the Chinese indigenous breeds were scattered in two different groups,
      irrespective of the farm origin. Faecal VFA concentrations were significantly
      affected by the pig breed. The proportion of acetate was higher in the Bama sows
      than in the other breeds. The real-time PCR analysis showed that 16S rRNA gene
      copies of total bacteria, Firmicutes and Bacteroidetes were significantly higher
      in the Bama sows compared to Xiaomeishan and Duroc sows. Both Meishan and
      Erhualian sows had higher numbers of total bacteria, Firmicutes, Bacteroidetes
      and sulphate-reducing bacteria as compared to Duroc sows. The results suggest
      that the pig breed affects the composition of gut microbiota. The microbial
      composition is different with different breeds, especially between overseas
      breeds (lean type) and Chinese breeds (relatively obese type). 

PMID- 25050030
TI  - Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative
      Damage in the Liver.
AB  - Alpha-lipoic acid (alpha-LA) is not only involved in energy metabolism, but is
      also a powerful antioxidant that can protect against hepatic oxidative stress
      induced by some drugs, toxins, or under various physiological and
      pathophysiological conditions. Here, we investigated the effect of alpha-LA
      against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1). Birds
      were randomly divided into four groups and assigned different diets: basal diet,
      300 mg/kg alpha-LA supplementation in basal diet, diet containing 74 MUg/kg AFB1,
      and 300 mg/kg alpha-LA supplementation in diet containing 74 MUg/kg AFB1, for 3
      weeks. The results revealed that the addition of 300 mg/kg alpha-LA protected
      against the liver function damage of broilers induced by chronic low dose of AFB1
      as estimated by a significant (p<0.05) change in levels of plasma total protein,
      albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic
      transaminase and glutamic-pyruvic transaminase. The histopathological analysis
      also showed that liver tissues were injured in the AFB1 diet, but this effect was
      alleviated by the addition of 300 mg/kg alpha-LA. Additionally, AFB1 induced a
      profound elevation of oxidative stress in birds, as indicated by an increase in
      malondialdehyde level, a decrease in glutathione peroxidase activity and a
      depletion of the glutathione content in the liver. All of these negative effects
      were inhibited by treatment with alpha-LA. Our results suggest that the
      inhibition of AFB1-induced excess production of lipid peroxides and the
      maintenance of intracellular antioxidant status may play important roles in the
      protective effects of alpha-LA against AFB1-induced oxidative damage in the
      liver. 

PMID- 25050031
TI  - Evaluation of amino Acid and energy utilization in feedstuff for Swine and
      poultry diets.
AB  - An accurate feed formulation is essential for optimizing feed efficiency and
      minimizing feed cost for swine and poultry production. Because energy and amino
      acid (AA) account for the major cost of swine and poultry diets, a precise
      determination of the availability of energy and AA in feedstuffs is essential for
      accurate diet formulations. Therefore, the methodology for determining the
      availability of energy and AA should be carefully selected. The total collection
      and index methods are 2 major procedures for estimating the availability of
      energy and AA in feedstuffs for swine and poultry diets. The total collection
      method is based on the laborious production of quantitative records of feed
      intake and output, whereas the index method can avoid the laborious work, but
      greatly relies on accurate chemical analysis of index compound. The direct
      method, in which the test feedstuff in a diet is the sole source of the component
      of interest, is widely used to determine the digestibility of nutritional
      components in feedstuffs. In some cases, however, it may be necessary to
      formulate a basal diet and a test diet in which a portion of the basal diet is
      replaced by the feed ingredient to be tested because of poor palatability and low
      level of the interested component in the test ingredients. For the digestibility
      of AA, due to the confounding effect on AA composition of protein in feces by
      microorganisms in the hind gut, ileal digestibility rather than fecal
      digestibility has been preferred as the reliable method for estimating AA
      digestibility. Depending on the contribution of ileal endogenous AA losses in the
      ileal digestibility calculation, ileal digestibility estimates can be expressed
      as apparent, standardized, and true ileal digestibility, and are usually
      determined using the ileal cannulation method for pigs and the slaughter method
      for poultry. Among these digestibility estimates, the standardized ileal AA
      digestibility that corrects apparent ileal digestibility for basal endogenous AA
      losses, provides appropriate information for the formulation of swine and poultry
      diets. The total quantity of energy in feedstuffs can be partitioned into
      different components including gross energy (GE), digestible energy (DE),
      metabolizable energy (ME), and net energy based on the consideration of
      sequential energy losses during digestion and metabolism from GE in feeds. For
      swine, the total collection method is suggested for determining DE and ME in
      feedstuffs whereas for poultry the classical ME assay and the precision-fed
      method are applicable. Further investigation for the utilization of ME may be
      conducted by measuring either heat production or energy retention using indirect
      calorimetry or comparative slaughter method, respectively. This review provides
      information on the methodology used to determine accurate estimates of AA and
      energy availability for formulating swine and poultry diets. 

PMID- 25050033
TI  - Reproductive Performance of Arabian and Thoroughbred Mares under Subtropical
      Conditions of Pakistan.
AB  - Breeding records of 57 Arabian and 66 Thoroughbred mares were analysed to assess
      their reproductive performance under the subtropical conditions of Pakistan. The
      Arabian mares showed significantly higher conception rates (p<0.05) in second
      mated oestrus and foal heat mated oestrus compared to Thoroughbred mares.
      However, conception rates for first lifetime mated oestrus were similar in both
      breeds of mares. Age at first mating (1,301+/-40 vs 1,500+/-32 days) was
      significantly (p<0.05) less in Arabian compared to Thoroughbred mares. Both
      breeds of mares showed significantly (p<0.05) higher frequencies of oestrous
      cycles and conception rates during the winter (October to March) compared to
      summer (June to August) months. Age of mares affected the conception rates, as
      mares at ages 3 to 7 and 8 to 12 years of ages had significantly higher
      conception rates (p<0.05) than those >=18 years old in both breeds. This study
      demonstrates that i) reproductive performance in Arabians is better than
      Thoroughbred mares under the subtropical conditions of Pakistan, ii) mares remain
      cyclic throughout the year and iii) conception rates were higher in mares bred
      during winter compared to summer months. 

PMID- 25050032
TI  - Genetic traceability of black pig meats using microsatellite markers.
AB  - Pork from Jeju black pig (population J) and Berkshire (population B) has a unique
      market share in Korea because of their high meat quality. Due to the high demand
      of this pork, traceability of the pork to its origin is becoming an important
      part of the consumer demand. To examine the feasibility of such a system, we aim
      to provide basic genetic information of the two black pig populations and assess
      the possibility of genetically distinguishing between the two breeds. Muscle
      samples were collected from slaughter houses in Jeju Island and Namwon, Chonbuk
      province, Korea, for populations J and B, respectively. In total 800 Jeju black
      pigs and 351 Berkshires were genotyped at thirteen microsatellite (MS) markers.
      Analyses on the genetic diversity of the two populations were carried out in the
      programs MS toolkit and FSTAT. The population structure of the two breeds was
      determined by a Bayesian clustering method implemented in structure and by a
      phylogenetic analysis in Phylip. Population J exhibited higher mean number of
      alleles, expected heterozygosity and observed heterozygosity value, and
      polymorphism information content, compared to population B. The FIS values of
      population J and population B were 0.03 and -0.005, respectively, indicating that
      little or no inbreeding has occurred. In addition, genetic structure analysis
      revealed the possibility of gene flow from population B to population J. The
      expected probability of identify value of the 13 MS markers was 9.87*10(-14) in
      population J, 3.17*10(-9) in population B, and 1.03*10(-12) in the two
      populations. The results of this study are useful in distinguishing between the
      two black pig breeds and can be used as a foundation for further development of
      DNA markers. 

PMID- 25050034
TI  - Fermentation Characteristics, Tannin Contents and In vitro Ruminal Degradation of
      Green Tea and Black Tea By-products Ensiled at Different Temperatures.
AB  - Green and black tea by-products, obtained from ready-made tea industry, were
      ensiled at 10 degrees C, 20 degrees C, and 30 degrees C. Green tea by-product
      silage (GTS) and black tea by-product silage (BTS) were opened at 5, 10, 45 days
      after ensiling. Fermentation characteristics and nutrient composition, including
      tannins, were monitored and the silages on day 45 were subjected to in vitro
      ruminal fermentation to assess anti-nutritive effects of tannins using
      polyethylene glycol (PEG) as a tannin-binding agent. Results showed that the GTS
      and BTS silages were stable and fermented slightly when ensiled at 10 degrees C.
      The GTS stored at 20 degrees C and 30 degrees C showed rapid pH decline and high
      acetic acid concentration. The BTS was fermented gradually with moderate change
      of pH and acid concentration. Acetic acid was the main acid product of
      fermentation in both GTS and BTS. The contents of total extractable phenolics and
      total extractable tannins in both silages were unaffected by storage
      temperatures, but condensed tannins in GTS were less when stored at high
      temperature. The GTS showed no PEG response on in vitro gas production, and
      revealed only a small increase by PEG on NH3-N concentration. Storage temperature
      of GTS did not affect the extent of PEG response to both gas production and NH3-N
      concentration. On the other hand, addition of PEG on BTS markedly increased both
      the gas production and NH3-N concentration at any ensiled temperature. It can be
      concluded that tannins in both GTS and BTS suppressed rumen fermentation, and
      tannins in GTS did more weakly than that in BTS. Ensiling temperature for both
      tea by-products did not affect the tannin's activity in the rumen. 

PMID- 25050035
TI  - Production of Endoglucanase, Beta-glucosidase and Xylanase by Bacillus
      licheniformis Grown on Minimal Nutrient Medium Containing Agriculture Residues.
AB  - Bacillus licheniformis was grown in minimal nutrient medium containing 1% (w/v)
      of distillers dried grain with soluble (DDGS), palm kernel meal (PKM), wheat bran
      (WB) or copra meal (CM), and the enzyme activity of endoglucanase, beta
      glucosidase, xylanase and reducing sugars was measured to investigate a
      possibility of using cost-effective agricultural residues in producing
      cellulolytic and hemicellulolytic enzymes. The CM gave the highest endoglucanase
      activity of 0.68 units/mL among added substrates at 48 h. CM yielded the highest
      titres of 0.58 units/ml of beta-glucosidase, compared to 0.33, 0.23, and 0.16
      units/mL by PKM, WB, and DDGS, respectively, at 72 h. Xylanase production was the
      highest (0.34 units/mL) when CM was added. The supernatant from fermentation of
      CM had the highest reducing sugars than other additional substrates at all
      intervals (0.10, 0.12, 0.10, and 0.11 mg/mL respectively). It is concluded that
      Bacillus licheniformis is capable of producing multiple cellulo- and
      hemicellololytic enzymes for bioethanol production using cost-effective
      agricultural residues, especially CM, as a sole nutrient source. 

PMID- 25050036
TI  - Effects of linseed oil or whole linseed supplementation on performance and milk
      Fatty Acid composition of lactating dairy cows.
AB  - The objective of this study was to determine the effects of linseed oil or whole
      linseed supplementation on performance and milk fatty acid composition of
      lactating dairy cows. Thirty six Holstein Friesian crossbred lactating dairy cows
      were blocked by milking days first and then stratified random balanced for milk
      yields and body weight into three groups of 12 cows each. The treatments
      consisted of basal ration (53:47; forage:concentrate ratio, on a dry matter [DM]
      basis, respectively) supplemented with 300 g/d of palm oil as a positive control
      diet (PO), or supplemented with 300 g/d of linseed oil (LSO), or supplemented
      with 688 g/d of top-dressed whole linseed (WLS). All cows were received ad
      libitum grass silage and individually fed according to the treatments. The
      experiment lasted for 10 weeks including the first 2 weeks as the adjustment
      period, followed by 8 weeks of measurement period. The results showed that LSO
      and WLS supplementation had no effects on total dry matter intake, milk yield,
      milk composition, and live weight change; however, the animals fed WLS had higher
      crude protein (CP) intake than those fed PO and LSO (p<0.05). To compare with the
      control diet, dairy cow's diets supplemented with LSO and WLS significantly
      increased milk concentrations of cis-9, trans-11-conjugated linoleic acid (CLA)
      (p<0.05) and n-3 fatty acids (FA) (p<0.01), particularly, cis-9,12,15-C18:3,
      C20:5n-3 and C22:6n-3. Supplementing LSO and WLS induced a reduction of medium
      chain FA, especially, C12:0-C16:0 FA (p<0.05) while increasing the concentration
      of milk unsaturated fatty acids (UFA) (p<0.05). Milk FA proportions of n-3 FA
      remarkably increased whereas the ratio of n-6 to n-3 decreased in the cows
      supplemented with WLS as compared with those fed the control diet and LSO
      (p<0.01). In conclusion, supplementing dairy cows' diet based on grass silage
      with WLS had no effect on milk yield and milk composition; however, trans-9-
      C18:1, cis-9, trans-11-CLA, n-3 FA and UFA were increased while saturated FA were
      decreased by WLS supplementation. Therefore, it is recommended that the addition
      300 g/d of oil from whole linseed should be used to lactating dairy cows' diets. 

PMID- 25050037
TI  - Effects of combination of rice straw with alfalfa pellet on milk productivity and
      chewing activity in lactating dairy cows.
AB  - An experiment was conducted to determine the effects of diets containing coarse
      texture rice straw and small particle size alfalfa pellets as a part of total
      mixed ration (TMR) on milk productivity and chewing activity in lactating dairy
      cows. Sixteen multiparous Holstein dairy cows (670+/-21 kg body weight) in mid
      lactation (194.1+/-13.6 days in milk) were randomly assigned to TMR containing
      50% of timothy hay (TH) or TMR containing 20% of rice straw and 30% of alfalfa
      pellet mixture (RSAP). Geometric mean lengths of TH and RSAP were found to be 5.8
      and 3.6, respectively. Dry matter intake, milk yield and milk composition were
      measured. Moreover, eating and ruminating times were recorded continuously using
      infrared digital camcorders. Milk yield and milk composition were not detected to
      have significant differences between TH and RSAP. Dry matter intake (DMI) did not
      significantly differ for cows fed with TH or RSAP. Although particle size of TH
      was larger than RSAP, eating, ruminating and total chewing time (min/d or min/kg
      of DMI) on TH and RSAP were similar. Taken together, our results suggest that
      using a proper amount of coarse-texture rice straw with high value nutritive
      alfalfa pellets may stimulate chewing activity in dairy cows without decreasing
      milk yield and composition even though the quantity of rice straw was 40% of TH. 

PMID- 25050038
TI  - Effects of a chelated copper as growth promoter on performance and carcass traits
      in pigs.
AB  - Three studies were conducted to investigate whether a chelated Cu can replace
      CuSO4 as a growth promoter in pigs. In Exp. 1, a total of 240 piglets (Large
      White*Landrace, 7.36+/-0.10 kg) were randomly allocated to 1 of 3 treatments with
      8 replicates and 10 piglets per pen. Treatments included a NRC control (CuSO4, 6
      mg/kg), two Cu supplementations from either CuSO4 or Cu(HMTBa)2 at 170 mg/kg.
      Pigs fed Cu(HMTBa)2 were 6.0% heavier than pigs fed either the NRC control or 170
      mg/kg CuSO4 (p = 0.03) at the end of the experiment. During the 42 days of
      experimental period, pigs fed Cu(HMTBa)2 gained 9.0% more (p = 0.01), tended to
      eat more feed (p = 0.09), and had better feed efficiency (p = 0.06) than those
      fed CuSO4. Compared with the 6 mg/kg CuSO4 NRC control, liver Cu was increased
      2.7 times with 170 mg/kg CuSO4 supplementation, and was further increased with
      Cu(HMTBa)2 (4.5 times, p<0.05). In Exp. 2, a total of 616 crossbred piglets (PIC,
      5.01+/-0.25 kg) were randomly allocated to 1 of 4 treatments with 7 replicates
      and 22 piglets per pen. Treatments included a NRC control (from CuSO4), and three
      pharmaceutical levels of Cu (150 mg/kg) supplemented either from CuSO4, tri-basic
      copper chloride (Cu2[OH]3Cl), or Cu(HMTBa)2. Pigs fed CuSO4 or Cu(HMTBa)2 had
      better feed efficiency (p = 0.01) and tended to gain more (p = 0.08) compared
      with those fed the NRC control. Pigs fed Cu2(OH)3Cl were intermediate. Pigs fed
      Cu(HMTBa)2 had the highest liver Cu, which was significantly higher than those
      fed (Cu2[OH]3Cl) or the negative control (p = 0.01). In Exp. 3, a total of 1,048
      pigs (PIC, 32.36+/-0.29 kg) were allotted to 6 treatments with 8 replicates per
      treatment and 20 to 22 pigs per pen. The treatments included a NRC control with 4
      mg/kg Cu from CuSO4, a positive control with 160 mg/kg Cu from CuSO4, and
      incremental levels of Cu(HMTBa)2 at 20, 40, 80, and 160 mg/kg. During the overall
      experimental period of 100 days, no benefit from 160 mg/kg CuSO4 was observed.
      Pigs fed Cu(HMTBa)2 had increased ADG (linear and quadratic, p<=0.05) and feed
      efficiency (linear and quadratic, p<=0.05) up to 80 mg/kg and no further
      improvement was observed at 160 mg/kg for the whole experimental period. Pigs fed
      80 mg/kg Cu(HMTBa)2 weighed 1.8 kg more (p = 0.07) and were 2.3 kg heavier in
      carcass (p<0.01) compared with pigs fed 160 mg/kg CuSO4. In addition, loin depth
      was increased with increased Cu(HMTBa)2 supplementation with pigs fed 80 mg/kg
      Cu(HMTBa)2 had the greatest loin depth (p<0.05). In summary, Cu(HMTBa)2 can be
      used to replace high CuSO4 as a growth promoter in nursery and grower-finisher
      pigs. 

PMID- 25050039
TI  - Effects of water restriction on the growth performance, carcass characteristics
      and organ weights of naked neck and ovambo chickens of southern Africa.
AB  - In semi-arid areas of Southern Africa, dehydration can compromise the performance
      and welfare of local chickens, particularly during the growing period when
      confinement is curtailed and birds are left to scavenge for feed and water. The
      effect of water restriction on the growth performance was compared in Naked Neck
      (NNK) and Ovambo (OVB) chickens that are predominant in Southern Africa. A total
      of 54 eight-wk-old pullets each of NNK and OVB chickens with an initial average
      weight of 641+/-10 g/bird were randomly assigned to three water intake
      treatments, each having six birds for 8 wk. The water restriction treatments were
      ad libitum, 70% of ad libitum and 40% of ad libitum intake. Nine experimental
      pens with a floor space of 3.3 m(2) per strain were used. The pens were housed in
      an open-sided house with cement floor deep littered with a 20 cm layer of
      untreated wood shavings. Feed was provided ad libitum. Average daily water intake
      (ADWI), BW at 16 weeks of age (FBW), ADG, ADFI, feed conversion ratio (FCR) and
      water to feed ratios (WFR) were determined. Ovambo chickens had superior (p<0.05)
      FBW, ADG and ADWI than NNK chickens. Body weight of birds at 16 weeks of age,
      ADG, ADFI, ADWI, and WFR declined progressively (p<0.05) with increasing severity
      of water restriction while FCR values increased (p<0.05) as the severity of water
      restriction increased. Naked Neck chickens had better FCR at the 40% of ad
      libitum water intake level than Ovambo chickens. The dressing percentage per bird
      was higher in water restricted birds than those on ad libitum water consumption,
      irrespective of strain. Heart weight was significantly lower in birds on 40% of
      ad libitum water intake than those on ad libitum and 70% of ad libitum water
      intake, respectively. In conclusion, NNK chickens performed better than OVB
      chickens under conditions of water restriction and would be ideal to raise for
      meat and egg production in locations where water shortages are a major challenge.

PMID- 25050040
TI  - Effects of functional oils on coccidiosis and apparent metabolizable energy in
      broiler chickens.
AB  - The objective of the present study was to investigate the effects of a mixture of
      functional oils (Essential, Oligo Basics Agroind. Ltda) on performance response
      of chickens challenged with coccidiosis and the determination of apparent
      metabolizable energy (AME), nitrogen-corrected apparent metabolizable energy
      (AMEn), the coefficients of protein and ether extract digestibility and
      intestinal morphology of broilers fed with diets containing Essential. In Exp. 1,
      a completely randomized design (CRD) was used, with one control diet without
      Essential inclusion with coccidiosis (Eimeria acervulina, Eimeria maxima, and
      Eimeria tenella) challenged birds and two different inclusion rates of Essential
      (1.5 kg/ton and 2 kg/ton) with coccidiosis-challenged and non-challenged birds
      for each inclusion rate, using 10 replicates and 50 birds per experimental unit.
      After 7 d of coccidiosis challenge, the livability was approximately 10% lower
      (p<0.05) for the control group. Intestinal lesion scores were lower (p<0.05) in
      the anterior intestine and the cecum for the chickens supplemented. Feed
      efficiency and growth rate were improved in birds supplemented with Essential
      (p<0.05) before the coccidiosis challenge and during the first 7 d post
      infection. In Exp. 2, a CRD was used, with one control diet without Essential
      inclusion and one diet with inclusion of Essential (1.5 kg/ton), using nine
      replications and 33 chicks per pen. The diets with Essential yielded
      approximately 4% higher AME (p = 0.003) and AMEn (p = 0.001). Essential
      supplementation increased villus height in the jejunum on d 14 (p<0.05). Villus
      height:crypt depth ratio for the supplemented birds was larger (p<0.05) in the
      jejunum on d 7, larger (p<0.05) in the jejunum and ileum on d 14. In conclusion,
      these functional oils improved the energy utilization and the livability and
      decreased lesions caused by coccidiosis in supplemented birds. 

PMID- 25050041
TI  - Ileal digestibility of amino acids in meat meal and soybean meal fed to growing
      pigs.
AB  - The objective of this experiment was to determine the concentration and
      digestibility of crude protein (CP) and amino acid (AA) in meat meal (MM), and to
      compare these values with the respective values in soybean meal (SBM). Six
      barrows (initial body weight = 66.9+/-3.8 kg) surgically fitted with a T-cannula
      at the distal ileum were allotted to a replicated 3*3 balanced Latin square
      design with 3 diets and 3 periods. Two experimental diets containing test
      ingredients as the sole source of AA were prepared to estimate the apparent ileal
      digestibility (AID) for CP and AA by the direct method. An N-free diet was also
      prepared to estimate basal endogenous losses of CP and AA. All experimental diets
      contained 5% chromic oxide as an indigestible index. Each period consisted of a 5
      d adaptation period and a 2-d of ileal digesta collection period. Ileal digesta
      samples were collected from 0900 to 1700 on d 6 and 7 of each period. The
      concentrations of CP, Lys, Met, and Trp in MM and SBM were analyzed to be 64.1,
      3.5, 1.1 and 0.6, and 45.6, 2.8, 0.8, and 0.3%, respectively. The AID of all AA
      except Gly in MM was less (p<0.05) than in SBM. The AID of Lys, Met, and Trp in
      MM was estimated to be 56.0, 71.7, and 47.1%, respectively. The SID of all AA in
      MM was less (p<0.05) than in SBM. The SID of Lys, Met, and Trp was 65.1, 79.2,
      and 78.5%, respectively. In conclusion, the CP and AA contents in MM were greater
      than those in SBM whereas the ileal digestibility of all AA in MM was less than
      in SBM. 

PMID- 25050042
TI  - Effects of Dietary Alpha-lipoic Acid and Acetyl-L-carnitine on Growth Performance
      and Meat Quality in Arbor Acres Broilers.
AB  - An experiment was conducted to evaluate the effects of dietary alpha-lipoic acid
      (LA) and acetyl-L-carnitine (ALC) on growth performance, carcass characteristics
      and meat quality in Arbor Acres broilers. A total of 486 1-d-old male Arbor Acres
      broilers were randomly allocated to 9 dietary treatments, 9 treatments were group
      A (0 mg/kg LA and 0 mg/kg ALC), group B (50 mg/kg LA and 0 mg/kg ALC), group C
      (100 mg/kg LA and 0 mg/kg ALC), group D (0 mg/kg LA and 50 mg/kg ALC), group E
      (50 mg/kg LA and 50 mg/kg ALC), group F (100 mg/kg LA and 50 mg/kg ALC), group G
      (0 mg/kg LA and 100 mg/kg ALC), group H (50 mg/kg LA and 100 mg/kg ALC), group I
      (100 mg/kg LA and 100 mg/kg ALC). Birds were slaughtered at 42 days old. Average
      daily gain (ADG), average feed intake (AFI), feed conversion rate (FCR),
      eviscerated rate, breast muscle percentage, thigh muscle percentage, abdominal
      fat percentage, liver weight, muscle color (L* value, a* value, b* value), pH
      values at 45 min and 24 h postmortem were measured. Results showed that there
      existed an interaction between LA and ALC in growth performance of broilers,
      carcass traits and meat quality. The overall result is that high level of LA and
      ALC led to lower AFI, ADG (p<0.01), lower abdominal fat percentage, liver weight
      (p<0.01), lower L* value, a* value, and b* value of breast muscle, L* value of
      thigh muscle (p<0.05), and higher FCR (p<0.01), eviscerated rate (p<0.01), breast
      muscle percentage, thigh muscle percentage (p<0.05), a* value, pH 45 min and pH
      24 h of thigh muscle (p<0.01). These results suggested that dietary LA and ALC
      contributed to the improvement of meat quality in broilers. 

PMID- 25050043
TI  - Comparison of methodologies to quantify phytate phosphorus in diets containing
      phytase and excreta from broilers.
AB  - The use of a suitable methodology to quantify the phytate phosphorus (Pphy)
      content in both the feed and the excreta from broilers is required to enable
      accurate calculation of the catalytic efficiency of the phytase supplemented in
      the feed. This study was conducted to compare 2 analytical methodologies
      (colorimetry and also high-performance liquid chromatography with a refractive
      index detector) in order to calculate the phytase efficiency by utilizing the
      results from the methodology that was shown to be the most appropriate. One
      hundred and twenty broilers were distributed in a (4+1)*2 factorial arrangement,
      corresponding to 4 diets that were equally deficient in P supplemented with
      increasing levels of phytase (0, 750, 1,500, and 2,250 units of phytase activity 
      FTU - per kg of feed) plus 1 positive control diet without phytase, supplied to
      male and female birds. The result indicated that the colorimetric methodology
      with an extraction ratio of 1:20 (mass of sample in g:volume of the solvent
      extractor in mL) was shown to be the most adequate. There was no interaction
      between the phytase level and the sex of the broilers (p>0.05). Males consumed
      12% more Pphy than did females (p<0.01), but the sex of the broilers did not
      affect (p>0.05) the excretion and retention coefficient of Pphy. The increase in
      the phytase level of the diet reduced (linear, p<0.01) the Pphy excretion. The
      greatest Pphy retention was estimated at 87.85% when the diet contained 1,950
      FTU/kg (p<0.01), indicating that it is possible to reduce the inorganic P in the
      formulation at an amount equivalent to 87.85% of the Pphy content present in the
      feed, which, in this research, corresponds to a decrease in 2.86 g of P/kg of the
      feed. 

PMID- 25050044
TI  - Kinetic Behavior of Escherichia coli on Various Cheeses under Constant and
      Dynamic Temperature.
AB  - In this study, we developed kinetic models to predict the growth of pathogenic
      Escherichia coli on cheeses during storage at constant and changing temperatures.
      A five-strain mixture of pathogenic E. coli was inoculated onto natural cheeses
      (Brie and Camembert) and processed cheeses (sliced Mozzarella and sliced Cheddar)
      at 3 to 4 log CFU/g. The inoculated cheeses were stored at 4, 10, 15, 25, and 30
      degrees C for 1 to 320 h, with a different storage time being used for each
      temperature. Total bacteria and E. coli cells were enumerated on tryptic soy agar
      and MacConkey sorbitol agar, respectively. E. coli growth data were fitted to the
      Baranyi model to calculate the maximum specific growth rate (MU max; log
      CFU/g/h), lag phase duration (LPD; h), lower asymptote (log CFU/g), and upper
      asymptote (log CFU/g). The kinetic parameters were then analyzed as a function of
      storage temperature, using the square root model, polynomial equation, and linear
      equation. A dynamic model was also developed for varying temperature. The model
      performance was evaluated against observed data, and the root mean square error
      (RMSE) was calculated. At 4 degrees C, E. coli cell growth was not observed on
      any cheese. However, E. coli growth was observed at 10 degrees C to 30 degrees C
      with a MU max of 0.01 to 1.03 log CFU/g/h, depending on the cheese. The MU max
      values increased as temperature increased, while LPD values decreased, and MU max
      and LPD values were different among the four types of cheese. The developed
      models showed adequate performance (RMSE = 0.176-0.337), indicating that these
      models should be useful for describing the growth kinetics of E. coli on various
      cheeses. 

PMID- 25050045
TI  - Effects of crossbreeding and gender on the carcass traits and meat quality of
      korean native black pig and duroc crossbred.
AB  - This study was conducted to observe the effects of crossbreeding and gender on
      the carcass traits and meat quality of Korean Native Black Pig (KNP) and
      KNP*Duroc crossbred (KNP*D). A total of 50 pigs comprising seven KNP barrows,
      eight KNP gilts, twenty KNP*D barrows and fifteen KNP*D gilts were used in this
      study. Animals were reared in the same housing condition with same feed diet for
      six months prior to slaughter. After an overnight chilling, the carcasses were
      graded, and samples of Musculus longissimus dorsi were obtained for meat quality
      analysis. The slaughter and carcass weights and dressing percentage of KNP*D were
      higher (p<0.001) than those of KNP. The slaughter and carcass weights and backfat
      thickness of barrows were higher (p<0.01) than those of gilts. There were no
      significant difference in carcass conformation and quality grade between KNP and
      KNP*D as well as barrow and gilt. Fat content of KNP*D was higher (p<0.001) than
      that of KNP. Fat content of barrow was higher (p<0.001) than that of gilt. There
      was interaction between crossbreeding and gender on the fat content. KNP gilt
      showed higher fat content than KNP barrow whereas KNP*D barrow showed higher fat
      content than KNP*D gilt. Lightness, redness, yellowness, chroma and hue angle
      values and color preference of meat of KNP*D were lower (p<0.001) than those of
      KNP. Redness, yellowness and chroma values of meat of barrow were lower (p<0.05)
      than those of gilt. It is concluded that crossbreeding KNP with Duroc increases
      carcass productivity and meat fat but decreases meat color values and preference.
      Crossbreeding of KNP with Duroc produces a better fat deposition in meat of
      barrows than in gilts. 

PMID- 25050046
TI  - Fatty Acid Composition and Sensory Characteristics of Eggs Obtained from Hens Fed
      Flaxseed Oil, Dried Whitebait and/or Fructo-oligosaccharide.
AB  - This study was conducted to assess the effects of flaxseed oil and dried
      whitebait as a source of omega-3 fatty acids (omega-3 FA), which could be used to
      produce eggs enriched with omega-3 FA, and of fructo-oligosaccharide (FOS) as a
      source of prebiotics on performance of hens (commercial Hy-Line Brown laying
      hens), and FA composition, internal quality, and sensory characteristics of the
      eggs. Dietary FOS increased egg weight. The amounts of alpha-linolenic (ALA),
      eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) in the eggs from the hens
      fed the flaxseed oil alone or flaxseed oil+dried whitebait diets were higher than
      those of the control. Hedonic scores for off-flavor, fishy flavor, buttery taste
      and overall acceptability of the eggs from the hens fed the diet containing
      flaxseed oil+ dried whitebait were lower (p<0.05) than those of the control.
      Overall acceptability of the eggs from the hens fed the diet containing soybean
      oil+dried whitebait was lower (p<0.05) than that of the control. However, all the
      sensory attributes of the eggs from the hens fed the diet containing flaxseed
      oil, dried whitebait and FOS were not significantly different from those of the
      control. These results confirmed that flaxseed oil increases the ALA content in
      the eggs and a combination of flaxseed oil and dried whitebait increases EPA and
      DHA in the eggs. Of significance was that addition of FOS to the flaxseed
      oil+dried whitebait diet improves the sensory characteristics of the eggs
      enriched with omega-3 FA. 

PMID- 25050048
TI  - Effects of light color on energy expenditure and behavior in broiler.
AB  - This study was conducted in order to investigate whether the presence of light or
      different colors of light would influence the energy expenditure and behavior of
      broiler chickens. Eight 8-week-old broiler chickens were adapted to a respiration
      chamber (Length, 28.5 cm; Height, 38.5 cm; Width, 44.0 cm) for one week prior to
      the initiation of the experiment. In experiment 1, energy expenditure and
      behavior of the chickens were analyzed in the presence or absence of light for
      four days. Chickens were exposed to 6 cycles of 2 h light/2 h dark period per
      day. In experiment 2, the broiler chickens that had been used in experiment 1
      were used to evaluate the effect of 4 different wavelength light-emitting diodes
      (LEDs) on the energy expenditure and behavior of broiler chickens. The LEDs used
      in this study had the following wavelength bands; white (control), red (618 to
      635 nm), green (515 to 530 nm) and blue (450 to 470 nm). The chickens were
      randomly exposed to a 2-h LED light in a random and sequential order per day for
      3 days. Oxygen consumption and carbon dioxide production of the chickens were
      recorded using an open-circuit calorimeter system, and energy expenditure was
      calculated based on the collected data. The behavior of the chickens was analyzed
      based on following categories i.e., resting, standing, and pecking, and closed
      circuit television was used to record these behavioral postures. The analysis of
      data from experiment 1 showed that the energy expenditure was higher (p<0.001) in
      chickens under light condition compared with those under dark condition. The
      chickens spent more time with pecking during a light period, but they frequently
      exhibited resting during a dark period. Experiment 2 showed that there was no
      significant difference in terms of energy expenditure and behavior based on the
      color of light (white, red, green, and blue) to which the chickens were exposed.
      In conclusion, the energy expenditure and behavior of broiler chickens were found
      to be strongly affected by the presence of light. On the other hand, there was no
      discernible difference in their energy expenditure and behavior of broiler
      chickens exposed to the different LED lights. 

PMID- 25050047
TI  - Effects of Acanthopanax senticosus Polysaccharide Supplementation on Growth
      Performance, Immunity, Blood Parameters and Expression of Pro-inflammatory
      Cytokines Genes in Challenged Weaned Piglets.
AB  - To investigate the effect of dietary Acanthopanax senticosus polysaccharide
      (ASPS) on growth performance, immunity, blood parameters and mRNA expression of
      pro-inflammatory cytokines in immunologically challenged piglets, an experiment
      employing 2*2 factorial arrangement concerning dietary ASPS treatment (0 or 800
      mg/kg) and immunological challenge (lipopolysaccharide [LPS] or saline injection)
      was conducted with 64 crossbred piglets (weaned at 28 d of age, average initial
      body weight of 7.25+/-0.21 kg) assigned to two dietary ASPS treatments with 8
      replicates of 4 pigs each. Half of the piglets of per dietary treatment were
      injected with LPS or saline on d 14. Blood samples were obtained at 3 h after
      immunological injection on d 14 and piglets were slaughtered to obtain spleen
      samples on d 21. Dietary ASPS did not affect average daily gain (ADG) (p =
      0.634), average daily feed intake (ADFI) (p = 0.655), and gain:feed (p = 0.814)
      prior to LPS challenge. After LPS challenge, for LPS-challenged pigs those fed
      ASPS had higher ADG and ADFI than the non-supplemented group (p<0.05), and an
      interaction between LPS*ASPS was observed on the two indices (p<0.05). Dietary
      ASPS improved lymphocyte proliferation among saline-injected and LPS-injected
      pigs (p<0.05). Interaction between LPS*ASPS was also revealed on lymphocyte
      proliferation (p<0.05). Circulatory concentration of IgG was influenced neither
      by ASPS (p = 0.803) or LPS (p = 0.692), nor their interaction (p = 0.289). Plasma
      concentration and spleen mRNA expression of interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), and tumor necrosis factor (TNF)-alpha were induced to
      increase (p<0.05) by LPS challenge, in contrast, these indices were decreased by
      dietary ASPS (p<0.05), and interactions were found on these cytokines (p<0.05).
      For LPS-challenged pigs, dietary ASPS also reduced the circulating concentration
      and spleen mRNA expression of IL-1beta, IL-6 as well as TNF-alpha (p<0.05). The
      interaction between LPS*ASPS was also observed on the circulating concentration
      of insulin-like growth factor- I, alpha-acid glycoprotein (alpha-AGP),
      nonesterified fatty acid, and glucose (p<0.05). The results of this study
      demonstrate that dietary ASPS can modulate the release of pro-inflammatory
      cytokines during immunological challenge, which might enable piglets to achieve
      better growth performance. 

PMID- 25050049
TI  - Factors Affecting Process Temperature and Biogas Production in Small-scale Rural
      Biogas Digesters in Winter in Northern Vietnam.
AB  - This study investigated the main factors influencing digester temperature and
      methods to reduce heat losses during the cold season in the subtropics. Four
      composite digesters (two insulated and two uninsulated) were buried underground
      to measure their internal temperature ( degrees C) at a depth of 140 cm and 180
      cm, biogas production and methane (CH4) concentration in biogas from August to
      February. In parallel the temperature of the air (100 cm above ground), in the
      slurry mixing tank and in the soil (10, 100, 140, and 180 cm depth) was measured
      by thermocouple. The influent amount was measured daily and the influent chemical
      composition was measured monthly during the whole experimental period. Seasonal
      variations in air temperature significantly affected the temperature in the soil,
      mixing tank and digester. Consequently, biogas production, which is temperature
      dependent, was influenced by the season. The main factors determining the
      internal temperature in the digesters were insulation with Styrofoam, air
      temperature and temperature of slurry in the mixing tank. Biogas production is
      low due to the cold climate conditions in winter in Northern Vietnam, but the
      study proved that storing slurry in the mixing tank until its temperature peak at
      around 14:00 h will increase the temperature in the digester and thus increase
      potential biogas production. Algorithms are provided linking digester temperature
      to the temperature of slurry in the mixing tank. 

PMID- 25050050
TI  - Nutritional factors affecting abdominal fat deposition in poultry: a review.
AB  - The major goals of the poultry industry are to increase the carcass yield and to
      reduce carcass fatness, mainly the abdominal fat pad. The increase in poultry
      meat consumption has guided the selection process toward fast-growing broilers
      with a reduced feed conversion ratio. Intensive selection has led to great
      improvements in economic traits such as body weight gain, feed efficiency, and
      breast yield to meet the demands of consumers, but modern commercial chickens
      exhibit excessive fat accumulation in the abdomen area. However, dietary
      composition and feeding strategies may offer practical and efficient solutions
      for reducing body fat deposition in modern poultry strains. Thus, the regulation
      of lipid metabolism to reduce the abdominal fat content based on dietary
      composition and feeding strategy, as well as elucidating their effects on the key
      enzymes associated with lipid metabolism, could facilitate the production of lean
      meat and help to understand the fat-lowering effects of diet and different
      feeding strategies. 

PMID- 25050052
TI  - FDA starts new light-touch inspections for some imports.
AB  - FDA starts light-touch inspections for some imports. 

PMID- 25050051
TI  - Conservative prescribing is needed to improve medication safety.
AB  - Conservative prescribing can improve medication safety. 

PMID- 25050054
TI  - Pharmaceutical approval update.
AB  - Apremilast (Otezla) for active psoriatic arthritis, omalizumab (Xolair) for
      chronic idiopathic urticaria, and grass pollen allergen extract (Oralair) for
      grass pollen-induced allergic rhinitis with or without conjunctivitis. 

PMID- 25050055
TI  - FDA Draft Guidances Compound the Compounding Uncertainty: A New List of 503B
      Outsourcing Facilities Offers No Guarantee of Anything.
AB  - Compounders who prepare nonpatient-specific prescriptions have been slow to sign
      up for a new FDA program meant to serve as a de facto "Good Housekeeping" seal of
      approval. Meanwhile, inspectors are turning up problems wherever they go. 

PMID- 25050056
TI  - Considerations for the appropriate use of skeletal muscle relaxants for the
      management of acute low back pain.
AB  - For patients with low back pain, skeletal muscle relaxants are often initiated
      after failure of first-line analgesics. However, these medications (reviewed in
      this article) are controversial alternatives that carry risks of adverse effects
      and increased cost. 

PMID- 25050058
TI  - The Medication Error Prioritization System (MEPS): A Novel Tool in Medication
      Safety.
AB  - An integrated health care system used an online database that captured
      pharmacists' reports of medication errors and an algorithm that helped classify
      and prioritize the information to identify patterns and improve safety outcomes. 

PMID- 25050057
TI  - Dietary supplements as disease-modifying treatments in osteoarthritis: a critical
      appraisal.
AB  - An array of natural substances purported to possess disease-modifying qualities
      for osteoarthritis are designated as "dietary supplements" and thus avoid
      rigorous FDA regulation. Substantial scientific evidence for the efficacy of
      these agents is elusive. 

PMID- 25050059
TI  - American association for cancer research and american psychiatric association.
AB  - The American Association for Cancer Research meeting included reports on new
      agents for breast cancer and melanoma. The American Psychiatric Association
      meeting offered updates on treatments for bipolar depression, autism, and
      depression. 

PMID- 25050060
TI  - Outcomes of 360 degrees  suture trabeculotomy with deep sclerectomy combined with
      cataract surgery for primary open angle glaucoma and coexisting cataract.
AB  - BACKGROUND: The purpose of this study was to investigate treatment outcomes in
      360 degrees  suture trabeculotomy with deep sclerectomy combined with
      phacoemulsification and aspiration and intraocular lens implantation (360P-LOT +
      DS). METHODS: Thirty-two eyes in 32 consecutive patients treated by 360P-LOT + DS
      for primary open angle glaucoma with coexisting cataracts at Sato Eye Clinic from
      March 2011 to April 2013 were retrospectively compared with 23 eyes in 23
      consecutive patients treated by cataract surgery and 120 degrees  trabeculotomy
      with deep sclerectomy (120P-LOT + DS) at the same clinic from January 2010 to
      February 2011. The parameters investigated during the 15 months after surgery
      were the course of intraocular pressure, number of antiglaucoma medications, best
      corrected visual acuity, and complications. RESULTS: Both groups showed a
      significant decrease in intraocular pressure starting at one month after surgery
      when compared with values before surgery. At 3, 6, 9, and 15 months after
      surgery, the intraocular pressure was significantly lower and the survival rate
      was significantly higher in the 360P-LOT + DS group compared with the 120P-LOT +
      DS group. The number of antiglaucoma medications, best-corrected visual acuity
      value, and complications did not differ significantly between the groups.
      CONCLUSION: Although the complications are similar to those seen in 120P-LOT +
      DS, treatment of primary open angle glaucoma and coexisting cataracts using 360P
      LOT + DS may yield better outcomes.

PMID- 25050061
TI  - Hypertensive phase and early complications after Ahmed glaucoma valve
      implantation with intraoperative subtenon triamcinolone acetonide.
AB  - OBJECTIVE: To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an
      adjunct to Ahmed glaucoma valve (AGV) implantation. DESIGN: Retrospective
      comparative case series. PARTICIPANTS: Forty-two consecutive cases of
      uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving
      intraoperative subtenon TA and 23 eyes that did not receive TA. METHODS: A
      retrospective chart review was performed on consecutive pseudophakic adult
      patients with uncontrolled glaucoma undergoing AGV with and without
      intraoperative subtenon TA injection by a single surgeon. Clinical data were
      collected from 42 eyes and analyzed for the first 6 months after surgery. MAIN
      OUTCOME MEASURES: Primary outcomes included intraocular pressure (IOP) and number
      of glaucoma medications prior to and after AGV implantation. The hypertensive
      phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or
      without medications) during the 6-month postoperative period that was not a
      result of tube obstruction, retraction, or malfunction. Postoperative
      complications and visual acuity were analyzed as secondary outcome measures.
      RESULTS: Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases
      developed the HP (P=0.027). Mean IOP (14.2+/-4.6 in TA cases versus [vs] 14.7+/
      5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed
      (1.8+/-1.3 in TA cases vs 1.6+/-1.1 in the comparison group; P=0.65) were similar
      between both groups at 6 months. Although rates of serious complications did not
      differ between the groups (13% in the TA group vs 16% in the non-TA group), early
      tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not
      in the non-TA group. CONCLUSIONS: Subtenon TA injection during AGV implantation
      may decrease the occurrence of the HP but does not alter the ultimate IOP outcome
      and may pose increased risk of serious complications within the first 6 months of
      surgery.

PMID- 25050062
TI  - Understanding benefits and addressing misperceptions and barriers to intrauterine
      device access among populations in the United States.
AB  - Three intrauterine devices (IUDs), one copper and two containing the progestin
      levonorgestrel, are available for use in the United States. IUDs offer higher
      rates of contraceptive efficacy than nonlong-acting methods, and several studies
      have demonstrated higher satisfaction rates and continuation rates of any birth
      control method. This efficacy is not affected by age or parity. The safety of
      IUDs is well studied, and the risks of pelvic inflammatory disease, perforation,
      expulsion, and ectopic pregnancy are all of very low incidence. Noncontraceptive
      benefits include decreased menstrual blood loss, improved dysmenorrhea, improved
      pelvic pain associated with endometriosis, and protection of the endometrium from
      hyperplasia. The use of IUDs is accepted in patients with multiple medical
      problems who may have contraindications to other birth control methods. Yet
      despite well-published data, concerns and misperceptions still persist,
      especially among younger populations and nulliparous women. Medical governing
      bodies advocate for use of IUDs in these populations, as safety and efficacy is
      unchanged, and IUDs have been shown to decrease unintended pregnancies.
      Dispersion of accurate information among patients and practitioners is needed to
      further increase the acceptability and use of IUDs. 

PMID- 25050064
TI  - Ethical and legal framework and regulation for off-label use: European
      perspective.
AB  - For more than 20 years the off-label use of drugs has been an essential part of
      the ethical and legal considerations regarding the international regulation of
      drug licensing. Despite a number of regulatory initiatives in the European Union,
      there seems to remain a largely unsatisfactory situation following a number of
      critical descriptions and statements from actors in the field. The present
      article gives an overview of the ethical and legal framework and developments in
      European countries and identifies existing problems and possible pathways for
      solutions in this important regulatory area. In addition to the presentation of
      the ethical and legal foundations, some attention is given to criticisms from
      medical practitioners to the current handling of off-label drug use. The review
      also focuses on the situation confronted by patients and physicians when off
      label prescriptions are necessary. Through legal descriptions from a number of
      countries, possible solutions for future discussion of European health care
      policy are selected and explained. 

PMID- 25050063
TI  - Comparative study of bioactivity of collagen scaffolds coated with graphene oxide
      and reduced graphene oxide.
AB  - BACKGROUND: Graphene oxide (GO) is a single layer carbon sheet with a thickness
      of less than 1 nm. GO has good dispersibility due to surface modifications with
      numerous functional groups. Reduced graphene oxide (RGO) is produced via the
      reduction of GO, and has lower dispersibility. We examined the bioactivity of GO
      and RGO films, and collagen scaffolds coated with GO and RGO. METHODS: GO and RGO
      films were fabricated on a culture dish. Some GO films were chemically reduced
      using either ascorbic acid or sodium hydrosulfite solution, resulting in
      preparation of RGO films. The biological properties of each film were evaluated
      by scanning electron microscopy (SEM), atomic force microscopy, calcium
      adsorption tests, and MC3T3-E1 cell seeding. Subsequently, GO- and RGO-coated
      collagen scaffolds were prepared and characterized by SEM and compression tests.
      Each scaffold was implanted into subcutaneous tissue on the backs of rats.
      Measurements of DNA content and cell ingrowth areas of implanted scaffolds were
      performed 10 days post-surgery. RESULTS: The results show that GO and RGO possess
      different biological properties. Calcium adsorption and alkaline phosphatase
      activity were strongly enhanced by RGO, suggesting that RGO is effective for
      osteogenic differentiation. SEM showed that RGO-modified collagen scaffolds have
      rough, irregular surfaces. The compressive strengths of GO- and RGO-coated
      scaffolds were approximately 1.7-fold and 2.7-fold greater, respectively, when
      compared with the non-coated scaffold. Tissue ingrowth rate was 39% in RGO-coated
      scaffolds, as compared to 20% in the GO-coated scaffold and 16% in the non-coated
      scaffold. CONCLUSION: In summary, these results suggest that GO and RGO coatings
      provide different biological properties to collagen scaffolds, and that RGO
      coated scaffolds are more bioactive than GO-coated scaffolds.

PMID- 25050065
TI  - Profile of saxagliptin in the treatment of type 2 diabetes: focus on Japanese
      patients.
AB  - Saxagliptin is a selective and potent dipeptidyl peptidase (DPP)-4 inhibitor,
      approved as an adjunct to diet and exercise to improve glycemic control in type 2
      diabetes mellitus (T2DM) in the USA on July 2009, and had been launched globally
      in over 86 countries by September 2013. In patients with T2DM, once-daily
      administration of saxagliptin before breakfast achieves sustained inhibition of
      plasma DPP-4 activity and reduction of postprandial hyperglycemia, including
      after dinner, associated with an increase in plasma glucagon-like peptide-1
      levels. This paper reviews the safety and efficacy of saxagliptin in Japanese
      patients with T2DM. The clinical development study in Japan supported its
      usefulness for the disease. Saxagliptin 1, 2.5, and 5 mg led to significant
      improvements in glycated hemoglobin (HbA1c), and was generally well tolerated.
      Treatment with saxagliptin 5 mg induced a sustained reduction in HbA1c over 52
      weeks. Long-term combination therapy with saxagliptin and other oral hypoglycemic
      agents also provided sustained glycemic control and was well tolerated for up to
      52 weeks. Saxagliptin as add-on to sulfonylureas or glinides has a tendency to
      increase hypoglycemia, but not with other oral antidiabetic agents, such as alpha
      glucosidase inhibitors, metformin, or thiazolidinediones. The results of clinical
      trials have confirmed the long-term efficacy and safety of saxagliptin
      monotherapy as well as its use as add-on combination therapy, and support its
      usefulness as a therapeutic agent for T2DM. Saxagliptin has less concern for
      hypoglycemia and weight gain, which often becomes problematic in routine care of
      T2DM. Meta-analysis of clinical trials in the USA showed no evidence of increased
      risk of cardiovascular events associated with saxagliptin, suggesting the
      superior of saxagliptin in terms of safety. Recently, investigators in the SAVOR
      TIMI (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with
      Diabetes Mellitus-Thrombolysis in Myocardial Infarction) 53 study suggested that
      DPP-4 inhibition with saxagliptin did not increase or decrease the rate of
      ischemic events, although the rate of hospitalization for heart failure was
      increased. Although saxagliptin improves glycemic control, other approaches are
      necessary to reduce cardiovascular risk in patients with diabetes. Saxagliptin is
      applicable for various pathological conditions, and is considered to be
      clinically significant as a new therapeutic option for Japanese patients with
      T2DM. 

PMID- 25050066
TI  - CP-673451, a platelet-derived growth-factor receptor inhibitor, suppresses lung
      cancer cell proliferation and migration.
AB  - Lung cancer is the leading cause of cancer mortality in the world. Although some
      advances in lung cancer therapy have been made, patient survival is still poor.
      The platelet-derived growth factor receptors (PDGFRs) and their ligands play
      critical roles in the regulation of many cancer cell processes, including cell
      survival and cell motility. Herein, we investigate the anticancer activities of
      CP-673451, a potent selective inhibitor of PDGFR kinase, in non-small-cell lung
      cancer (NSCLC) therapy. We found that CP-673451 is effective at suppressing cell
      viability, inducing cell apoptosis, and inhibiting cell migration and invasion by
      suppressing the PDGFR downstream signaling pathway in NSCLC cells. Furthermore,
      CP-673451 is effective at suppressing NSCLC tumor growth in vivo. In summary, our
      studies suggest that CP-673451 might be a promising therapeutic compound for
      NSCLC. 

PMID- 25050067
TI  - Lack of association between the XPD Lys751Gln polymorphism and colorectal cancer
      risk: a meta-analysis.
AB  - BACKGROUND: The xeroderma pigmentosum complementary group D (XPD) gene has been
      linked to the development of colorectal cancer (CRC) through disruption of DNA
      repair. Several studies have suggested that the XPD polymorphism Lys751Gln is
      associated with an increased risk of developing CRC. However, previous results
      remain inconclusive. Herein, we performed a meta-analysis to evaluate the
      potential for this relationship. METHODS: Relevant studies were retrieved from
      the PubMed database. Strict selection and exclusion criteria were determined, and
      the odds ratio with a 95% confidence interval was used to assess the strength of
      associations. The fixed or random effects model was selected on the basis of
      heterogeneity tests among studies. Publication bias was estimated using funnel
      plots and Egger's regression test. RESULTS: The meta-analysis included 2,961
      cases and 4,539 controls from eleven studies. The results indicated that the XPD
      Lys751Gln polymorphism had no association with CRC risk for all genetic models
      (Gln-Gln versus Lys-Lys, P=0.477; Lys-Gln versus Lys-Lys, P=0.283; Lys-Gln + Gln
      Gln versus Lys-Lys, P=0.562), even when compared within subgroups based on
      ethnicity and source of controls. CONCLUSION: Based on the results of our meta
      analysis, there is no evidence of a link between the XPD Lys751Gln polymorphism
      and risk of CRC.

PMID- 25050068
TI  - Discordance rate of HER2 status in primary breast carcinomas versus synchronous
      axillary lymph node metastases: a multicenter retrospective investigation.
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is considered to be a
      therapeutic and prognostic marker in the management of breast carcinoma (BC),
      although discordance rates between primary and metastatic or locally recurrent
      lesions have been reported. METHODS: One hundred and forty-eight paraffin
      embedded BC tissues from patients of mean age 59.27 (33-96) years and
      corresponding synchronous lymph node metastases were collected and
      retrospectively studied using immunohistochemistry and fluorescence in situ
      hybridization to evaluate HER2 status. Fleiss-Cohen weighted k statistics were
      used to assess the concordance rate between HER2 status of the primary BC and the
      synchronous metastatic lesions. RESULTS: The overall concordance rate for HER2
      was 95.28%. Eighty-nine cases were concordantly HER2-negative in primary BC and
      nodal metastases, and 52 cases were HER2-positive in both primary and metastatic
      tumors. Changes in HER2 status between primary BC and corresponding synchronous
      metastases were observed in seven (4.72%) cases. Three of the discordant cases
      were HER2-negative in the primary tumor and HER2-positive in the metastases,
      while four cases were HER2-positive in the primary BC and HER2-negative in the
      metastases. No significant correlations were identified between HER2 status and
      expression of hormone receptors, growth fraction (Ki-67), or other
      histopathological parameters (pT, pN, grade). CONCLUSION: Simultaneous
      determination of HER2 in BC and corresponding metastatic lymph nodes is not
      mandatory, but may strongly influence the therapeutic management. It was
      demonstrated that loss of HER2 amplification results in worse post-relapse
      survival and overall survival in BC patients and, on the other hand, a gain in
      HER2 expression in metastatic lymph nodes of BC may allow the possibility of a
      targeted treatment. Thus, our opinion is that significant prognostic information
      may be obtained by simultaneous assessment of HER2 status in both primary and
      synchronous metastatic BC.

PMID- 25050069
TI  - Clinical utility of trabectedin for the treatment of ovarian cancer: current
      evidence.
AB  - Among the pharmaceutical options available for treatment of ovarian cancer,
      attention has been increasingly focused on trabectedin (ET-743), a drug which
      displays a unique mechanism of action and has been shown to be active in several
      human malignancies. Currently, single agent trabectedin is approved for treatment
      of patients with advanced soft tissue sarcoma after failure of anthracyclines and
      ifosfamide, and in association with pegylated liposomal doxorubicin for treatment
      of patients with relapsed partially platinum-sensitive ovarian cancer. This
      review aims at summarizing the available evidence about the clinical role of
      trabectedin in the management of patients with epithelial ovarian cancer. Novel
      perspectives coming from a better understanding of trabectedin mechanisms of
      action and definition of patients subgroups likely susceptible to benefit of
      trabectedin treatment are also presented. 

PMID- 25050070
TI  - Cost-effectiveness of continuous erythropoietin receptor activator in anemia.
AB  - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are the mainstay of anemia
      therapy. Continuous erythropoietin receptor activator (CERA) is a highly
      effective, long-acting ESA developed for once-monthly dosing. A multitude of
      clinical studies has evaluated the safety and efficiency of this treatment option
      for patients with renal anemia. In times of permanent financial pressure on
      health care systems, the cost-effectiveness of CERA should be of particular
      importance for payers and clinicians. OBJECTIVE: To critically analyze, from the
      nephrologists' point of view, the published literature focusing on the cost
      effectiveness of CERA for anemia treatment. METHODS: The detailed literature
      search covered electronic databases including MEDLINE, PubMed, and Embase, as
      well as international conference abstract databases. RESULTS: Peer-reviewed
      literature analyzing the definite cost-effectiveness of CERA is scarce, and most
      of the available data originate from conference abstracts. Identified data are
      restricted to the treatment of anemia due to chronic kidney disease. Although the
      majority of studies suggest a considerable cost advantage for CERA, the published
      literature cannot easily be compared. While time and motion studies clearly
      indicate that a switch to CERA could minimize health care staff time in dialysis
      units, the results of studies comparing direct costs are more ambivalent,
      potentially reflecting the differences between health care systems and
      variability between centers. CONCLUSION: Analyzed data are predominantly
      insufficient; they miss clear evidence and have to thus be interpreted with great
      caution. In this day and age of financial restraints, results from well-designed,
      head-to-head studies with clearly defined endpoints have to prove whether CERA
      therapy can achieve cost savings without compromising anemia management.

PMID- 25050071
TI  - Alogliptin in combination with metformin and pioglitazone for the treatment of
      type 2 diabetes mellitus.
AB  - Alogliptin is a selective dipeptidyl peptidase-4 inhibitor recently marketed for
      once-daily administration in the treatment of type 2 diabetes mellitus (T2DM).
      Fixed-dose combinations of alogliptin with both metformin and pioglitazone are
      also commercially available, providing a measure of convenience in addition to an
      effective mode of delivering combination therapy to improve glycemic control.
      Alogliptin has been studied clinically as initial therapy in treatment-naive
      patients with T2DM and as initial therapy or add-on in combination with other
      antidiabetic agents. Clinical trial data with alogliptin demonstrate clinical
      efficacy in terms of glycosylated hemoglobin A1c and fasting plasma glucose
      reductions when used both as monotherapy and as a component of two- or three-drug
      combination regimens for the treatment of T2DM. Extensive Phase II and Phase III
      clinical trial data support the use of alogliptin in combination with metformin
      and pioglitazone. Glycemic reduction with both combinations is similar to the sum
      of the respective monotherapies, with adverse event rates similar - or more
      moderate - than those observed with up-titration of monotherapy or the addition
      of other antihyperglycemic agents. 

PMID- 25050072
TI  - Abdominal obesity: causal factor or simply a symptom of obesity-related health
      risk.
AB  - BACKGROUND: Abdominal fat (AF) reduction is advocated in the treatment of obesity
      related diseases. Nonetheless, recent studies have shown additional beneficial
      effects against obesity-related health risks, independent of AF reduction.
      Therefore it is important to determine whether AF plays a causal role in
      promoting metabolic disorders or is simply a symptom of increased obesity-related
      health risk factors. Clarification of the primary role of AF in the pathogenesis
      of obesity-related disease is also important. OBJECTIVE: This retrospective study
      was conducted with the objectives of 1) comparison between groups exhibiting
      equivalent amounts of AF loss that resulted from distinct treatments (exercise
      and dietary restriction) with respect to degrees of improvement in obesity
      related health risk factors and 2) determination of definite differences in the
      outcomes of obesity-related health risk in subjects receiving identical treatment
      (exercise) but exhibiting a remarkable difference in AF reduction. DESIGN: In 66
      subjects who completed a 12-week exercise or dietary restriction program, 17
      parameters (systolic blood pressure [SBP] and diastolic blood pressure [DBP];
      high-sensitivity C-reactive protein [hs-CRP]; leptin, adiponectin, tumor necrosis
      factor [TNF]-alpha, interleukin [IL]-6; alanine aminotransferase [ALT], gamma
      glutamyl transpeptidase [gammaGT]; lipid profile: high-density lipoprotein
      cholesterol [HDLC], triglyceride [TG]; fasting plasma glucose [FPG], hemoglobin
      A1c [HbA1c], homeostasis model assessment of insulin resistance (HOMA-IR);
      creatinine, uric acid; and maximal aerobic capacity [VO2 max]) were examined as
      indicators of obesity-related health risk. RESULTS: Despite equivalent magnitudes
      of AF reduction (-29.5% versus -30.1%) in subjects in the exercise and dietary
      restriction groups (objective 1), ten parameters (SBP, DBP, HDLC, HOMA-IR, uric
      acid, creatinine, hs-CRP, adiponectin, IL-6, and VO2 max) showed significant
      differences. However, for large AF reduction differences (-30.1% versus -2.8%)
      between groups of subjects in the same exercise program (objective 2), only
      creatinine and VO2 max were different. CONCLUSION: It is likely that AF reduction
      alone is not directly linked to improvement in obesity-related health risk
      factors, indicating the need for reexamination of the management for AF reduction
      (ie, lifestyle modification) rather than simply targeting reduction of AF.

PMID- 25050073
TI  - The effect of vagal nerve blockade using electrical impulses on glucose
      metabolism in nondiabetic subjects.
AB  - PURPOSE: Vagal interruption causes weight loss in humans and decreases endogenous
      glucose production in animals. However, it is unknown if this is due to a direct
      effect on glucose metabolism. We sought to determine if vagal blockade using
      electrical impulses alters glucose metabolism in humans. PATIENTS AND METHODS: We
      utilized a randomized, cross-over study design where participants were studied
      after 2 weeks of activation or inactivation of vagal nerve blockade (VNB). Seven
      obese subjects with impaired fasting glucose previously enrolled in a long-term
      study to examine the effect of VNB on weight took part. We used a standardized
      triple-tracer mixed meal to enable measurement of the rate of meal appearance,
      endogenous glucose production, and glucose disappearance. The 550 kcal meal was
      also labeled with (111)In-diethylene triamine pentaacetic acid (DTPA) to measure
      gastrointestinal transit. Insulin action and beta-cell responsivity indices were
      estimated using the minimal model. RESULTS: Integrated glucose, insulin, and
      glucagon concentrations did not differ between study days. This was also
      reflected in a lack of effect on beta-cell responsivity and insulin action.
      Furthermore, fasting and postprandial endogenous glucose production, integrated
      meal appearance, and glucose disposal did not differ in the presence or absence
      of VNB. Similarly, gastric emptying and colonic transit were unchanged by VNB.
      CONCLUSION: In this pilot study in nondiabetic humans, electrical vagal blockade
      had no acute effects on glucose metabolism, insulin secretion and action, or
      gastric emptying. It remains to be determined if more pronounced effects would be
      observed in diabetic subjects.

PMID- 25050074
TI  - Efficacy and tolerance of lactitol supplementation for adult constipation: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Constipation is a common complaint in adults. Lactitol is an osmotic
      disaccharide laxative that increases fecal volume and stimulates peristalsis. In
      this paper, we present the first meta-analysis on the efficacy and tolerance of
      lactitol for adult constipation. METHODS: We searched MEDLINE((r)) and Embase,
      with no date or language restrictions, for studies of lactitol supplementation on
      adult constipation. A random-effects meta-analysis was performed on pre- to
      posttreatment changes in stool frequency and consistency with lactitol among all
      studies, as well as a comparison of efficacy and tolerance outcomes in randomized
      controlled trials (RCTs) of lactitol versus lactulose. RESULTS: A total of eleven
      studies representing 663 distinct patients were included in the final analysis,
      including five single-arm studies, four RCTs comparing lactitol with lactulose,
      one RCT comparing lactitol with placebo, and one nonrandomized controlled trial
      comparing lactitol with stimulant laxatives. Weekly stool frequency was
      significantly increased with lactitol compared with baseline (standardized mean
      difference [SMD]: 1.56, P<0.001). Stool consistency also improved over the
      supplementation period with lactitol (SMD: 1.04, P<0.001). Approximately one
      third of patients experienced an adverse event; however, symptoms were generally
      mild and rarely (5%) resulted in study withdrawal. In RCTs of lactitol versus
      lactulose, lactitol was slightly more effective than lactulose in increasing
      weekly stool frequency (SMD: 0.19, P=0.06). No statistically significant
      differences between lactitol and lactulose were identified in any other efficacy
      or tolerance outcome. Lactitol demonstrated favorable efficacy and tolerance in
      individual studies when compared to stimulant laxatives and placebo. CONCLUSION:
      Lactitol supplementation is well tolerated and improves symptoms of adult
      constipation. The efficacy and tolerance of lactitol and lactulose are similar,
      with a trend for more frequent stools with lactitol. Limited evidence suggests
      lactitol is superior to stimulant laxatives and placebo for relieving
      constipation symptoms.

PMID- 25050075
TI  - Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of
      the rat bone cancer pain model.
AB  - Metastatic bone cancer causes severe pain, but current treatments often provide
      insufficient pain relief. One of the reasons is that mechanisms underlying bone
      cancer pain are not solved completely. Our previous studies have shown that brain
      derived neurotrophic factor (BDNF), known as a member of the neurotrophic family,
      is an important molecule in the pathological pain state in some pain models. We
      hypothesized that expression changes of BDNF may be one of the factors related to
      bone cancer pain; in this study, we investigated changes of BDNF expression in
      dorsal root ganglia in a rat bone cancer pain model. As we expected, BDNF mRNA
      (messenger ribonucleic acid) and protein were significantly increased in L3
      dorsal root ganglia after intra-tibial inoculation of MRMT-1 rat breast cancer
      cells. Among the eleven splice-variants of BDNF mRNA, exon 1-9 variant increased
      predominantly. Interestingly, the up-regulation of BDNF is localized in small
      neurons (mostly nociceptive neurons) but not in medium or large neurons (non
      nociceptive neurons). Further, expression of nerve growth factor (NGF), which is
      known as a specific promoter of BDNF exon 1-9 variant, was significantly
      increased in tibial bone marrow. Our findings suggest that BDNF is a key molecule
      in bone cancer pain, and NGF-BDNF cascade possibly develops bone cancer pain. 

PMID- 25050076
TI  - Computational prognostic indicators for breast cancer.
AB  - Breast cancer remains the leading cause of cancer-related mortality in women.
      Comprehensive genomics, proteomics, and metabolomics studies are emerging that
      offer an opportunity to model disease biology, prognosis, and response to
      specific therapies. Although many biomarkers have been identified through
      advances in data mining techniques, few have been applied broadly to make patient
      specific decisions. Here, we review a selection of breast cancer prognostic
      indicators and their implications. Our goal is to provide clinicians with a
      general evaluation of emerging computational methodologies for outcome
      prediction. 

PMID- 25050078
TI  - Effect of age and sex on warfarin dosing.
AB  - OBJECTIVE: We examined the potential effect of sex and age on warfarin dosing in
      ambulatory adult patients. METHODS: We conducted a retrospective chart review of
      patients attending an anticoagulation clinic. We included patients anticoagulated
      with warfarin for atrial fibrillation or venous thromboembolism who had a
      therapeutic international normalized ratio of 2-3 for 2 consecutive months. We
      excluded patients who had been on any drug that is known to have a major
      interaction with warfarin, smokers, and heavy alcohol consumers. Out of 340
      screened medical records, 96 met the predetermined inclusion criteria. The
      primary outcome assessed was warfarin total weekly dose (TWD). RESULTS: There was
      a statistically significant difference in the TWD among the ages (P<0.01); older
      patients required lower doses. However there was no statistically significant
      difference in the TWD between sexes (P=0.281). CONCLUSION: Age was found to have
      a significant effect on warfarin dosing. Even though women did require a lower
      TWD than men, this observation was not statistically significant.

PMID- 25050077
TI  - Intrauterine nutrition: long-term consequences for vascular health.
AB  - There is a growing body of evidence that improper intrauterine nutrition may
      negatively influence vascular health in later life. Maternal malnutrition may
      result in intrauterine growth retardation and, in turn, metabolic disorders such
      as insulin resistance, diabetes, hypertension, and dyslipidemia, and also
      enhanced risk of atherosclerosis and cardiovascular death in the offspring.
      Energy and/or protein restriction is the most critical determinant for fetal
      programming. However, it has also been proposed that intrauterine n-3 fatty acid
      deficiency may be linked to later higher blood pressure levels and reduced
      insulin sensitivity. Moreover, it has been shown that inadequate supply of
      micronutrients such as folate, vitamin B12, vitamin A, iron, magnesium, zinc, and
      calcium may contribute to impaired vascular health in the progeny. In addition,
      hypertensive disorders of pregnancy that are linked to impaired placental blood
      flow and suboptimal fetal nutrition may also contribute to intrauterine growth
      retardation and aggravated cardiovascular risk in the offspring. On the other
      hand, maternal overnutrition, which often contributes to obesity and/or diabetes,
      may result in macrosomia and enhanced cardiometabolic risk in the offspring.
      Progeny of obese and/or diabetic mothers are relatively more prone to develop
      obesity, insulin resistance, diabetes, and hypertension. It was demonstrated that
      they may have permanently enhanced appetites. Their atheromatous lesions are
      usually more pronounced. It seems that, particularly, a maternal high-fat/junk
      food diet may be detrimental for vascular health in the offspring. Fetal exposure
      to excessive levels of saturated fatty and/or n-6 fatty acids, sucrose, fructose
      and salt, as well as a maternal high glycemic index diet, may also contribute to
      later enhanced cardiometabolic risk. 

PMID- 25050079
TI  - Association of positive fluid balance and cardiovascular complications after
      thoracotomy for noncancer lesions.
AB  - OBJECTIVE: The purpose of this study was to explore the influence of positive
      fluid balance on cardiovascular complications after thoracotomy for noncancer
      lesions. METHODS: After approval from an institutional review board, a
      retrospective cohort study was conducted. All consecutive patients undergoing
      thoracotomy between January 1, 2005 and December 31, 2011 in a single medical
      center were recruited. The primary outcome of the study was the incidence of
      cardiovascular complications, which were defined as cardiac arrhythmia, cardiac
      arrest, heart failure, myocardial ischemia, and pulmonary embolism. Univariable
      and multivariable risk regression analyses were used to evaluate the association
      between positive fluid balance and cardiovascular complications. RESULTS: A total
      of 720 patients were included in this study. The incidence of cardiovascular
      complications after thoracotomy for noncancer lesions was 6.7% (48 of 720).
      Patients with positive fluid balance >2,000 mL had a significantly higher
      incidence of cardiovascular complications than those with positive fluid balance
      <=2,000 mL (22.2% versus 7.0%, P=0.005). Cardiac arrhythmias were the most common
      complication. Univariable risk regression showed that positive fluid balance
      >2,000 mL was a significant risk factor (risk ratio =3.15, 95% confident interval
      [CI] =1.44-6.90, P-value =0.004). After adjustment for all potential confounding
      variables during multivariable risk regression analysis, positive fluid balance
      >2,000 mL remained a strong risk factor for cardiovascular complications (risk
      ratio =2.18, 95% CI =1.36-3.51, P-value =0.001). Causes of positive fluid balance
      >2,000 mL included excessive hemorrhage (48%), hypotension without excessive
      hemorrhage (29.6%), and liberal fluid administration (22.4%). CONCLUSION:
      Positive fluid balance was a significant risk factor for cardiovascular
      complications. Strategies to minimize positive fluid balance during surgery for
      patients at high risk of cardiovascular complications include preparing adequate
      blood and blood products, considering appropriate hemoglobin level as a
      transfusion trigger, and adjusting the optimal dose of local anesthetic for
      intraoperative thoracic epidural analgesia.

PMID- 25050080
TI  - Sleep-wake disturbances in cancer patients: narrative review of literature
      focusing on improving quality of life outcomes.
AB  - PURPOSE: Evidence suggests a high prevalence of sleep-wake disturbances in
      patients with cancer, occurring at diagnosis, during treatment, and continuing to
      survivorship. Yet associations between sleep-wake disturbances and the impact on
      quality of life outcomes is less clear. The purpose of this narrative review of
      the literature is to evaluate sleep-wake disturbances in patients with cancer, to
      describe the influence of poor sleep on quality of life as an outcome, and to
      evaluate the evidence to recommend future interventions. FRAMEWORK AND METHODS:
      This review was guided by the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) approach. Four databases (CINAHL, MEDLINE, PsycINFO,
      and Embase) were searched using terms "cancer OR neoplasm", "sleep, sleep
      disturbance, sleep disorders or insomnia", and "quality of life"; the search
      included all years, English language, and peer-reviewed articles on research
      studies. Studies included measurements of sleep and quality of life in cancer
      patients at a minimum of two time points and demonstrated relationships between
      sleep and quality of life. Data were collected on date, patient demographics,
      cancer type and treatment, timeframe, design, measurement, variables, and
      results. RESULTS: This narrative review demonstrates that sleep-wake disturbance
      is a major problem/symptom in patients with cancer. Of the 18 studies included,
      measurement of sleep-related variables included objective and subjective
      measures; however, direct measurement of the associations between sleep and
      quality of life was not common. Cognitive behavioral therapy for insomnia and
      mind-body interventions demonstrated feasibility when implemented into cancer
      care settings. In addition, the majority of interventions exhibited moderate
      effectiveness in improving sleep-wake disturbance and quality of life outcomes.
      CONCLUSION: The studies predominantly reported that poor sleep negatively impacts
      quality of life. The intervention studies included nonpharmacologic interventions
      such as cognitive behavioral treatment and mind-body and exercise interventions
      with moderate-to-high levels of evidence for improvement in sleep measures and
      quality of life.

PMID- 25050081
TI  - Rhenium Complexes with Red-Light-Induced Anticancer Activity.
AB  - Rhenium(I) pyridocarbazole complexes with photoinduced antiproliferative activity
      are reported. The substitutionally inert complexes induce cell death by singlet
      oxygen generation upon irradiation with red light (lambda >= 620 nm), while only
      weak background cytotoxicity is observed in the dark. Due to their ability to
      inhibit protein kinases (nanomolar IC50 values against Pim1 at 10 MUM ATP), this
      class of rhenium complexes point into the direction of dual function
      antiproliferative therapy with a single drug in which photodynamic therapy is
      combined with the inhibition of cancer related protein kinases.

PMID- 25050082
TI  - The impact of rescue or maintenance therapy with EGFR TKIs for Stage IIIb-IV non
      squamous non-small-cell lung cancer patients requiring mechanical ventilation.
AB  - BACKGROUND: The toxicity of epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors (TKIs) is less than that of cytotoxic agents. The reports of
      dramatic response and improvement in performance status with the use of EGFR TKIs
      may influence a physician's decision-making for patients with non-squamous non
      small cell lung cancer (NSCLC) and life-threatening respiratory distress. The aim
      of this study was to evaluate the outcome of rescue or maintenance therapy with
      EGFR TKI for stage IIIb-IV non-squamous NSCLC patients requiring mechanical
      ventilation. METHODS: Eighty-three Asian patients with stage IIIb-IV non-squamous
      NSCLC and who required mechanical ventilation between June 2005 and January 2010
      were evaluated. RESULTS: Of the 83 patients, 16 (19%) were successfully weaned
      from the ventilator. The use of EGFR TKI as rescue or maintenance therapy during
      respiratory failure did not improve the rate of successful weaning (standard care
      18% vs. with EGFR TKI, 22%; p = 0.81) in univariate and multivariate analyses.
      CONCLUSIONS: Rescue or maintenance therapy with EGFR TKI for stage IIIb-IV non
      squamous NSCLC patients requiring mechanical ventilation was not associated with
      better outcome. An end-of-life discussion should be an important aspect in the
      care of this group of patients, since only 19% were successfully weaned from
      mechanical ventilation.

PMID- 25050083
TI  - A meaningful daily life in nursing homes - a place of shelter and a space of
      freedom: a participatory appreciative action reflection study.
AB  - BACKGROUND: Shortcomings in elderly care have been reported in many parts of the
      world, including Sweden. However, national guidelines for elderly care have been
      introduced in Sweden, which contain core values and local guarantees of dignity.
      These highlight the need for dignity and well-being, and organising the older
      person's daily life so that they perceive it as meaningful. Therefore, the aim of
      the present study was to describe older persons' experience and knowledge about
      obstacles, opportunities and solutions to developing a meaningful daily life for
      those living in nursing homes. METHODS: This study combined the Participatory
      Appreciative Action Reflection (PAAR) and hermeneutic approaches. Twenty-five
      older persons participated and persons with dementia or cognitive impairments
      were included. Repeated interviews were carried out as reflective conversations,
      leaving 50 interviews in total, wherein the older persons provided their analyses
      and reflections on a meaningful daily life. Finally, an analysis of the data was
      completed based on a life-world hermeneutic approach. RESULTS: We identified five
      tentative interpretations that describe obstacles, opportunities and solutions
      for a meaningful daily life. Themes 2 and 4 outline obstacles for a meaningful
      daily life, and Themes 1, 3 and 5 describe opportunities and solutions for a
      meaningful daily life: (1) Having space to be yourself; (2) No space to be
      yourself; (3) Belonging and security; (4) A feeling of insecurity; and (5)
      Longing for something to happen. In the main interpretation, we found that the
      five tentative interpretations are related to Tuan's concepts of space and place,
      where place can be described as security and stableness, and space as freedom and
      openness. CONCLUSIONS: The reciprocal relationship is a solution for a meaningful
      daily life and occurs in the interaction between staff and older persons in
      nursing homes. It is the balance of power, and constitutes a place of shelter and
      a space of freedom for a meaningful daily life. The older person must have
      balance between shelter and freedom to have a meaningful daily life.

PMID- 25050085
TI  - Silk peptide treatment can improve the exercise performance of mice.
AB  - BACKGROUND: We previously reported that silk peptide (SP) treatment led to
      increased resting fat oxidation in exercised mice. However, it was not known
      whether SP treatment could effectively increase exercise capacity. Accordingly,
      this study aimed to examine whether SP treatment affected energy metabolism
      during exercise in addition to exercise performance. METHODS: We randomized 36 7
      week-old male ICR mice into 2 groups: the control (n = 18) and SP (n = 18)
      groups. All mice were trained by treadmill running 5 times per week for 2 weeks.
      SP was dissolved in distilled water and daily 800-mg/kg body weight doses before
      the running exercise were oral administered intraperitoneally to the SP group for
      2 weeks. [Formula: see text] was measured before and after the 2 weeks training
      period. We also assessed energy metabolism during exercise for 1 h after the 2
      week training period. In addition to blood samples, liver glycogen and
      gastrocnemius-white and gastrocnemius-red muscle was obtained at the following 3
      time points: at rest, immediately after exercise, and 1-hour post exercise.
      RESULTS: The [Formula: see text] max after 2 weeks of training was significantly
      increased (8%) in the SP group compared to the baseline; a similar result was not
      observed in the CON group. The sum of fat oxidation during a 1-h period tended to
      be 13% higher in the SP group than in the CON group (P < 0.077). In particular,
      the sum of fat oxidation was significantly higher in the SP group during the
      initial 20-min phase than that in the CON group (P < 0.05). The glycogen
      concentration in the white gastrocnemius muscle did not differ between the groups
      either rest or after 1 h of exercise but was significantly higher in the SP group
      than in the CON group during the recovery period (1 h post-exercise completion).
      CONCLUSIONS: These results suggest that SP treatment can improve the exercise
      performance. Therefore, SP is considered to confer beneficial effects upon
      athletes, in whom exercise abilities are required.

PMID- 25050084
TI  - Do economic evaluation studies inform effective healthcare resource allocation in
      Iran? A critical review of the literature.
AB  - To aid informed health sector decision-making, data from sufficient high quality
      economic evaluations must be available to policy makers. To date, no known study
      has analysed the quantity and quality of available Iranian economic evaluation
      studies. This study aimed to assess the quantity, quality and targeting of
      economic evaluation studies conducted in the Iranian context. The study
      systematically reviewed full economic evaluation studies (n = 30) published
      between 1999 and 2012 in international and local journals. The findings of the
      review indicate that although the literature on economic evaluation in Iran is
      growing, these evaluations were of poor quality and suffer from several major
      methodological flaws. Furthermore, the review reveals that economic evaluation
      studies have not addressed the major health problems in Iran. While the
      availability of evidence is no guarantee that it will be used to aid decision
      making, the absence of evidence will certainly preclude its use. Considering the
      deficiencies in the data identified by this review, current economic evaluations
      cannot be a useful source of information for decision makers in Iran. To improve
      the quality and overall usefulness of economic evaluations we would recommend; 1)
      developing clear national guidelines for the conduct of economic evaluations, 2)
      highlighting priority areas where information from such studies would be most
      useful and 3) training researchers and policy makers in the calculation and use
      of economic evaluation data. 

PMID- 25050086
TI  - One-step synthesis of platinum nanoparticles loaded in alginate bubbles.
AB  - Composite particles with multifunctions have been extensively utilized for
      various applications. Bubble particles can be applied for ultrasound-mediated
      imaging, drug delivery, absorbers, cell culture, etc. This study proposes a one
      step strategy to obtain Pt nanoparticles loaded in alginate bubbles. A needle
      based droplet formation was used to generate uniform alginate particles about 2
      mm in diameter. The hydrolysis reaction of NaBH4 was utilized to produce gaseous
      hydrogen and then trapped within alginate particles to form bubbles. The Pt(4+)
      mixed with alginate solution was dropped into the reservoir to react with
      reducing NaBH4 and hardening CaCl2 to form Pt nanoparticles-alginate composite
      bubbles. Results indicate that the size of bubbles decreases with the CaCl2
      concentration (1% ~ 20%), and size of bubbles increases with the NaBH4
      concentration (1 ~ 20 mM). The advantages for the present approach include low
      cost, easy operation, and effective production of Pt nanoparticles-alginate
      composite bubbles. 

PMID- 25050088
TI  - Electrochemical growth of Co nanowires in ultra-high aspect ratio InP membranes:
      FFT-impedance spectroscopy of the growth process and magnetic properties.
AB  - The electrochemical growth of Co nanowires in ultra-high aspect ratio InP
      membranes has been investigated by fast Fourier transform-impedance spectroscopy
      (FFT-IS) in the frequency range from 75 Hz to 18.5 kHz. The impedance data could
      be fitted very well using an electric circuit equivalent model with a series
      resistance connected in series to a simple resistor-capacitor (RC) element and a
      Maxwell element. Based on the impedance data, the Co deposition in ultra-high
      aspect ratio InP membranes can be divided into two different Co deposition
      processes. The corresponding share of each process on the overall Co deposition
      can be determined directly from the transfer resistances of the two processes.
      The impedance data clearly show the beneficial impact of boric acid on the Co
      deposition and also indicate a diffusion limitation of boric acid in ultra-high
      aspect ratio InP membranes. The grown Co nanowires are polycrystalline with a
      very small grain size. They show a narrow hysteresis loop with a preferential
      orientation of the easy magnetization direction along the long nanowire axis due
      to the arising shape anisotropy of the Co nanowires. 

PMID- 25050089
TI  - Photocatalytic reduction synthesis of SrTiO3-graphene nanocomposites and their
      enhanced photocatalytic activity.
AB  - SrTiO3-graphene nanocomposites were prepared via photocatalytic reduction of
      graphene oxide by UV light-irradiated SrTiO3 nanoparticles. Fourier transformed
      infrared spectroscopy analysis indicates that graphene oxide is reduced into
      graphene. Transmission electron microscope observation shows that SrTiO3
      nanoparticles are well assembled onto graphene sheets. The photocatalytic
      activity of as-prepared SrTiO3-graphene composites was evaluated by the
      degradation of acid orange 7 (AO7) under a 254-nm UV irradiation, revealing that
      the composites exhibit significantly enhanced photocatalytic activity compared to
      the bare SrTiO3 nanoparticles. This can be explained by the fact that
      photogenerated electrons are captured by graphene, leading to an increased
      separation and availability of electrons and holes for the photocatalytic
      reaction. Hydroxyl (.OH) radicals were detected by the photoluminescence
      technique using terephthalic acid as a probe molecule and were found to be
      produced over the irradiated SrTiO3 nanoparticles and SrTiO3-graphene composites;
      especially, an enhanced yield is observed for the latter. The influence of
      ethanol, KI, and N2 on the photocatalytic efficiency was also investigated. Based
      on the experimental results, .OH, h(+), and H2O2 are suggested to be the main
      active species in the photocatalytic degradation of AO7 by SrTiO3-graphene
      composites. PACS: 61.46. + w; 78.67.Bf; 78.66.Sq.

PMID- 25050090
TI  - The Surgeon and his Experience Remain Paramount.

PMID- 25050091
TI  - A clinical pathway for total shoulder arthroplasty-a pilot study.
AB  - BACKGROUND: Appropriate pain management after total shoulder arthroplasty (TSA)
      facilitates rehabilitation and may improve clinical outcomes. QUESTIONS/PURPOSES:
      This prospective, observational study evaluated a multimodal analgesia clinical
      pathway for TSA. METHODS: Ten TSA patients received an interscalene nerve block
      (25 cm(3) 0.375% ropivacaine) with intraoperative general anesthesia.
      Postoperative analgesia included regularly scheduled non-opioid analgesics
      (meloxicam, acetaminophen, and pregabalin) and opioids on demand (oral oxycodone
      and intravenous patient-controlled hydromorphone). Patients were evaluated twice
      daily to assess pain, anterior deltoid strength, handgrip strength, and sensory
      function. RESULTS: The nerve block lasted an average of 18 h. Patients had
      minimal pain after surgery; 0 (median score on a 0-10 scale) in the Post
      Anesthesia Care Unit (PACU) but increased on postoperative day (POD) 1 to 2.3
      (0.0, 3.8; median (25%, 75%)) at rest and 3.8 (2.1, 6.1) with movement. Half of
      the patients activated the patient-controlled analgesia four or fewer times in
      the first 24 h after surgery. Operative anterior deltoid strength was 0 in the
      PACU but returned to 68% by POD 1. Operative hand strength was 0 (median) in the
      PACU, but the third quartile (75%) had normalized strength 49% of preoperative
      value. CONCLUSIONS: Patients did well with this multimodal analgesic protocol.
      Pain scores were low, half of the patients used little or no intravenous opiate,
      and some patients had good handgrip strength. Future research can focus on
      increasing duration of analgesia from the nerve block, minimizing motor block,
      lowering pain scores, and avoiding intravenous opioids.

PMID- 25050092
TI  - The Surgeon's Role in Relative Success of PCL-Retaining and PCL-Substituting
      Total Knee Arthroplasty.
AB  - BACKGROUND: The orthopedic literature has not shown a universal and replicated
      difference, outside of flexion, in clinical results between posterior cruciate
      ligament retention and posterior cruciate ligament substitution in total knee
      arthroplasty. QUESTIONS/PURPOSES: This study was performed to compare the
      restoration of flexion and knee function in a large series of cruciate-retaining
      and cruciate-substituting total knee arthroplasties (TKRs). In addition, we aimed
      to study how other variables, such as those unique to each surgeon, may have
      affected the results. PATIENTS AND METHODS: The current study evaluated 8,607
      total knee arthroplasties in 5,594 patients performed by six surgeons, each using
      one of four prosthesis designs (two posterior cruciate ligament retaining, two
      posterior cruciate ligament substituting). Knees were compared at the level of
      cruciate-retaining and cruciate-substituting knees, at the level of the four
      prostheses, and at the level of surgeon-implant combinations. Least squared means
      scores were obtained through multiple linear regression, analysis of variance,
      and the maximum likelihood method. RESULTS: At the level of posterior cruciate
      ligament treatment, posterior cruciate ligament substitution as a whole showed
      3.2 degrees  greater flexion than posterior cruciate ligament retention. At the
      prosthesis level, cruciate-substituting models provided greater flexion and
      cruciate-retaining models provided higher function scores. In the surgeon-implant
      combinations, surgeons provided mixed results that often did not reflect findings
      from other levels; one surgeon's use of a posterior cruciate ligament retaining
      prosthesis achieved 14.7 degrees  greater flexion than the surgeon's use of a
      corresponding posterior cruciate ligament substituting design. CONCLUSIONS:
      Posterior cruciate ligament treatment is confounded by other variables, including
      the operating surgeon. The arthroplasty surgeon should choose a prosthesis based,
      not only on outside results, but also on personal experience and comfort.

PMID- 25050093
TI  - The Surgeon and his Experience is the Thing!

PMID- 25050094
TI  - The use of biologic DMARDs identifies rheumatoid arthritis patients with more
      optimistic expectations of total knee arthroplasty.
AB  - BACKGROUND: Preoperative expectations of total knee arthroplasty (TKA) correlate
      with postsurgical satisfaction, and are linked to outcomes. Rheumatoid arthritis
      (RA), and other chronic diseases, may lower expectations, although new biologic
      medications have greatly enhanced patients' quality of life. QUESTIONS/PURPOSES:
      The purpose of this study is to compare preoperative expectations of RA to those
      of matched osteoarthritis (OA) patients undergoing TKA, and examine the subset of
      RA on biologic DMARD therapy. METHODS: For a cross-sectional study, RA and OA
      identified from an institutional TKA registry were matched on age, sex, prior
      TKA, and preoperative function. Expectations were measured using the Hospital for
      Special Surgery (HSS) Knee Expectations Survey. Expectations and quality of life
      measures were assessed preoperatively and scores were compared between RA and OA.
      RESULTS: One hundred fourteen RA cases, 46.5% on biologics, were matched to 228
      OA cases. The average expectations score was not significantly lower for RA
      compared to OA (72.9 +/- 20.7 vs. 77.2 +/- 18.3, p = 0.040. RA on biologics had
      expectations similar to OA (total expectation score 76.3 +/- 18.1 vs. 77.4 +/-
      17.4, p = 0.71), while RA not on biologics had expectations that were
      significantly lower (69.9 +/- 22.4 vs. 77.1 +/- 19.0, p = 0.03). CONCLUSION: Use
      of biologics in RA patients was associated with higher expectations, similar to
      those of OA patients, but the effect on outcomes is not known. Further studies
      should assess the effect of higher expectations in RA patients on outcomes.

PMID- 25050096
TI  - Clinical outcomes in patients with pulmonary hypertension undergoing total hip
      arthroplasty.
AB  - BACKGROUND: Pulmonary hypertension (PH) is regarded as a risk factor for
      perioperative complications in patients undergoing noncardiac surgery.
      QUESTIONS/PURPOSES: The objective of this retrospective case-control study was to
      evaluate the adverse outcomes of pulmonary hypertension patients undergoing
      elective unilateral hip replacements. METHODS: We performed a retrospective case
      control study of total hip replacement patients with pulmonary hypertension
      (cases) and without pulmonary hypertension (control). From the years 2003 to
      2008, we identified a total of 132 patients undergoing primary total hip
      replacements with a diagnosis of pulmonary hypertension (right ventricular
      systolic pressure >35). The primary outcome assessed was the incidence of adverse
      events that occurred during the postoperative hospital stay. Secondary outcomes
      studied included length of hospital stay, mortality, and ability to reach certain
      physical therapy milestones. RESULTS: The PH group had significantly more adverse
      events than the control group. Nonlethal cardiac dysrhythmias comprised the most
      common adverse outcome among the PH group. Overall, the PH group had a morbidity
      rate of 34.7% while the control had a rate of 21%. The PH group had longer
      hospital stay (6.7 days vs. 5.9). Both groups had zero mortality during the
      hospital stay. The PH group had comparable rehabilitation recovery times than the
      control group. CONCLUSION: This retrospective case-control study demonstrates
      that pulmonary hypertension patients undergoing total hip arthroplasty are more
      prone to adverse outcomes, especially cardiac dysrhythmias, and longer hospital
      stays.

PMID- 25050095
TI  - Blood management may have an impact on length of stay after total hip
      arthroplasty.
AB  - BACKGROUND: The steady rise in demand for total hip arthroplasty constitutes a
      significant and increasing burden on health care resources. The biggest
      contributors to the total cost of hip replacement procedures other than the price
      of the implant are hospital stay and postoperative rehabilitation. Blood
      management is one of the most adjustable factors that can impact length of stay
      and cost-efficiency while improving patient safety. QUESTIONS/PURPOSES: The
      primary purpose of this retrospective study was to assess the potential impact of
      blood management interventions on length of hospital stay after primary
      unilateral total hip arthroplasty. This was achieved by first identifying which
      patient and surgical factors are associated with an increased risk of prolonged
      hospital stay. Subsequently, the significant factors were controlled for through
      a multivariate regression analysis to quantify the association between blood
      transfusions and increased hospital stay. METHODS: Retrospectively, the study
      included 2,104 primary total hip replacements. Eight hundred eighty-eight
      procedures were performed on males and 1,216 on females, with a mean age of 64
      years at the time of the surgery (range 18-94 years) and BMI of 28.6 kg/m(2)
      (range 12-51.5 kg/m(2)). The correlation between each factor and length of stay
      was analyzed separately using univariate regression analysis. Those variables
      with p <= 0.05 in the univariate model were selected for inclusion in the
      multivariate logistic regressions. Multiple linear regression was used to analyze
      the effect of each significant factor and derive odds ratios with adjustment for
      the other variables. RESULTS: Multivariate Poisson regression revealed that
      increased length of stay was significantly correlated to patient age (p = 0.05),
      the use of coumadin (p = 0.02) or lovenox/heparin (p = 0.007) as opposed to
      aspirin for anticoagulation, and allogeneic blood transfusion (p < 0.0001). The
      data shows that allogeneic blood transfusion is associated with a longer hospital
      stay regardless of absolute drop in hemoglobin level postoperatively or at
      discharge or the number of units transfused (OR = 1.18, 95% CI = 1.09 to 1.28, p
      < 0.001). CONCLUSION: Transfusion of allogeneic blood is independently associated
      with increased hospital stay after total hip arthroplasty. Blood management
      modalities that can significantly reduce transfusion risk could impact length of
      stay as well as the total cost of hip replacement procedures.

PMID- 25050097
TI  - Corticosteroid and Anesthetic Injections for Muscle Strains and Ligament Sprains
      in the NFL.
AB  - BACKGROUND: Administering local anesthetic or corticosteroid injections in
      professional athletes to allow return to play is common but has traditionally
      been viewed as suspect and taboo. The skepticism surrounding therapeutic
      injections stems predominantly from anecdotal experience as opposed to scientific
      data. QUESTIONS/PURPOSES: The purpose of this paper is to evaluate the current
      use of corticosteroid injections for muscle strains and ligaments sprains in the
      National Football League to document player's ability to return to play and
      possible adverse effects. PATIENTS AND METHODS: Athletes from a single National
      Football League team who received at least one corticosteroid or anesthetic
      injection for either a muscle strain or ligament sprain during three consecutive
      seasons were retrospectively reviewed. Thirty-seven injections were given over
      the three seasons. Injections were either performed blindly or by using
      ultrasound guidance. RESULTS: Twice as many defensive players were injected than
      offensive players. The average number of days of conservative treatment before
      injection was 6.5 days. All players returned to play after injection. There were
      no complications from any of the injections. Seventeen (55%) players did not miss
      a single game, and nine (30%) did not miss a single day. Quadriceps strains were
      associated with the most missed games (four) and the most missed days (36.5).
      Proximal hamstring strains were second with an average of three missed games and
      28 missed days. CONCLUSION: Corticosteroid injections are a safe and effective
      therapeutic intervention for treating muscle strains and ligament sprains in
      order to enable athletes to return to competition earlier.

PMID- 25050098
TI  - Compartment syndrome: diagnosis, management, and unique concerns in the twenty
      first century.
AB  - BACKGROUND: Compartment syndrome is an elevation of intracompartmental pressure
      to a level that impairs circulation. While the most common etiology is trauma,
      other less common etiologies such as burns, emboli, and iatrogenic injuries can
      be equally troublesome and challenging to diagnose. The sequelae of a delayed
      diagnosis of compartment syndrome may be devastating. All care providers must
      understand the etiologies, high-risk situation, and the urgency of intervention.
      QUESTIONS/PURPOSES: This study was conducted to perform a comprehensive review of
      compartment syndrome discussing etiologies, risk stratification, clinical
      progression, noninvasive and invasive monitoring, documentation, medical-legal
      implication, and our step-by-step approach to compartment syndrome prevention,
      detection, and early intervention. METHODS: A literature search was performed
      using the PubMed Database and the following search terms: "Compartment syndrome
      AND Extremity," "Compartment syndrome AND Gluteal," and Compartment syndrome AND
      Paraspinal." A total of 2,068 articles were identified. Filters allowed for the
      exclusion of studies not printed in English (359) and those focusing on
      exertional compartment syndrome (84), leaving a total of 1,625 articles available
      for review. RESULTS: The literature provides details regarding the etiologies,
      risk stratification, clinical progression, noninvasive and invasive monitoring,
      documentation, medical-legal implication, and our step-by-step approach to
      compartment syndrome prevention, detection, and early intervention. The
      development and progression of compartment syndrome is multifactorial, and as
      complexity of care increases, the opportunity for the syndrome to be missed is
      increased. Recent changes in the structure of in-hospital medical care including
      resident work hour restrictions and the incorporation of midlevel providers have
      increased the frequency of "signouts" or "patient handoffs" which present
      opportunities for the syndrome to be mismanaged. CONCLUSION: The changing
      dynamics of the health care team have prompted the need for a more explicit
      algorithm for managing patients at risk for compartment syndrome to ensure
      appropriate conveyance of information among team members.

PMID- 25050099
TI  - Tarsal Coalitions: Radiographic, CT, and MR Imaging Findings.
AB  - BACKGROUND: Tarsal coalitions affect up to 13% of the population and can be a
      cause of chronic ankle and hindfoot pain. They can be subdivided as osseous,
      cartilaginous, or fibrous types, each with unique radiographic, CT, and MR
      imaging findings. In particular, MR imaging offers the unique ability to
      determine the exact type of tarsal coalition that is present as well as whether
      any associated soft tissue abnormalities are present. QUESTIONS/PURPOSES: The
      purposes of this paper were to (1) review the anatomy of the hindfoot; (2) review
      the radiographic, CT, and MR imaging findings of tarsal coalitions; and (3)
      review the imaging appearance of the specific types of tarsal coalitions.
      METHODS: Online searches were performed using Google Scholar with the search
      criteria of "tarsal coalition," "hindfoot anatomy," and "subtalar coalition," and
      limiting the searches to papers published in the last 10 years in major radiology
      journals. RESULTS: The anatomy of the hindfoot is complex but essential to
      understand. There are various radiographic, CT, and MR imaging findings that can
      be consistently noted in cases of tarsal coalition. The specific types of tarsal
      coalition demonstrate characteristic imaging findings. CONCLUSIONS: Knowledge of
      the normal anatomy of the foot, in particular the hindfoot, combined with the
      knowledge of the imaging characteristics of different histologic subtypes of
      coalitions (osseous, cartilaginous, and fibrous) is essential for interpreting
      radiographic, CT, and MR images of the ankle and foot.

PMID- 25050101
TI  - A patient with severe pulmonary hypertension for hip arthroplasty.

PMID- 25050100
TI  - The Influence of Obesity on the Outcome of TKR: Can the Impact of Obesity be
      justified from the Viewpoint of the Overall Health Care System?
AB  - BACKGROUND: There is controversy in the literature regarding the justification of
      performing total knee replacement (TKR) in obese patients in view of their
      increased risk of poor outcomes and how those poorer outcomes impact the health
      care system overall. QUESTIONS/PURPOSES: Is TKR justifiable in the obese patient?
      Can the negative impact of continuing to perform TKR in the obese be quantified?
      METHODS: A Cochrane Library, PubMed (MEDLINE), and Google Scholar search related
      to the justification of TKR in the obese patient and its impact on the health
      care system was analyzed. The main criteria for selection were that the articles
      were focused in the aforementioned questions. RESULTS: Two thousand one hundred
      seventy-three articles were found, but only 50 were selected and reviewed because
      they were focused on the questions of this paper. Although some articles (with
      low grade of evidence) did not find that obesity adversely affected the outcome
      of TKR, most of them found that obesity adversely affected the results of TKR.
      Regarding complications rates and survival rates, obesity has shown to have a
      negative influence on outcome after TKR. The improvements in patient-reported
      outcome measures, however, were similar irrespective of body mass index.
      Regarding the impact of TKR in obese patients, an extra cost of US$3,050 has been
      reported per patient. Considering that 50% of the US population is obese and that
      600,000 TKRs are implanted per year, the impact for the US health system could be
      as much as 915 million dollars (300,000 * 3,050). CONCLUSION: TKR in obese
      patients may be justifiable because the functional improvements appear equivalent
      to those of patients with a lower BMI. However, in obese patients, the risk of
      complications is higher and the prosthetic survival is lower. Moreover, TKR in
      obese patients has a huge impact on the health system which should be considered.

PMID- 25050102
TI  - Chronic infection leading to failure of a composite femoral stem: a report of two
      cases.

PMID- 25050103
TI  - Extensive posterior-inferior heterotopic ossification in chronic grade v
      acromioclavicular injury blocking reduction during surgical repair: a report of
      two cases.

PMID- 25050104
TI  - Osteoid osteoma of the triquetrum: a case of four-year delay in diagnosis.

PMID- 25050106
TI  - Medical futility in the era of evidence-based medicine.

PMID- 25050107
TI  - An emerging role for Hippo-YAP signaling in cardiovascular development.
AB  - The Hippo signaling pathway was originally discovered in Drosophila and shown to
      be critical for organ size control and tumorigenesis. This pathway consists of a
      cascade of kinases and several adaptors that lead to the phosphorylation and
      inhibition, through nuclear exclusion, of the transcriptional cofactor Yorkie in
      Drosophila or YAP (yes associated protein) in mammals. Recent studies demonstrate
      that cardiac-specific deletion of the Hippo pathway kinase Mst (STE20-like
      protein kinases) co-activator WW45 (WW domain-containing adaptor 45), Mst1, Mst2,
      or Lats2 (large tumor suppressor homologue 2) in mice result in over-grown hearts
      with elevated cardiomyocyte proliferation. Consistent with these observations,
      over-expression of YAP in the mouse embryonic heart increases heart size and
      promotes cardiac regeneration and contractility after myocardial infarction by
      inducing cardiomyocyte proliferation, whereas deletion of YAP in the mouse heart
      impedes cardiomyocyte proliferation, causing myocardial hypoplasia and embryonic
      or premature lethality. YAP has also been shown to play an important role in the
      vascular system. Specific-deletion of YAP from vascular smooth muscle cells in
      mice results in aberrant development of large arteries with a hypoplastic
      arterial wall phenotype. Hippo-YAP signaling cross-talks with other signaling
      pathways such as IGF (insulin-like growth factor) and Wnt signaling to promote
      heart growth by increasing expression of cell cycle genes. The purpose of this
      review is to summarize these recent findings and discuss potential diagnostic or
      therapeutic strategies in cardiovascular system based on manipulating the Hippo
      YAP signaling. 

PMID- 25050108
TI  - Marked elevation of B-type natriuretic peptide in patients with heart failure and
      preserved ejection fraction.
AB  - Marked elevations of B-type natriuretic peptide (BNP) are not generally seen in
      patients with heart failure and preserved ejection fraction (HFpEF). The
      objective of this study was to examine the clinical and laboratory
      characteristics of a large cohort of patients with HFpEF and markedly elevated
      BNP. A retrospective examination of 421 inpatients at a university hospital
      admitted with a diagnosis of HFpEF was performed. Clinical and echocardiographic
      data in 4 groups of patients with levels of BNP <= 100 pg/mL, 100-400 pg/mL, 400
      1,000 pg/mL and > 1,000 pg/mL were compared. Patients with HFpEF and BNP > 1,000
      pg/mL (28% of the population) were characterized by impaired renal function and
      greater use of anti-hypertensive medications. A subset of these patients with BNP
      > 1,000 pg/mL had normal renal function (21%) and were significantly older, more
      frequently female, and tended to have lower ejection fractions. Conversely,
      patients with HFpEF and BNP <= 100 pg/mL were younger and had preserved renal
      function. BNP was inversely related to the likelihood of subsequent admission for
      heart failure, but not to myocardial infarction or death. IN CONCLUSION: BNP >
      1,000 pg/mL is seen in almost 1/3 of patients hospitalized with HFpEF. This
      elevation of BNP often reflects impaired renal function, but can also be seen in
      patients with preserved renal function but relatively impaired systolic function.

PMID- 25050109
TI  - Relationship between brachial-ankle pulse wave velocity and metabolic syndrome
      components in a Chinese population.
AB  - The purpose of this study was to assess the relationship between arterial
      stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), and the
      presence of the metabolic syndrome (MS) in a Chinese population. A total of 4,445
      subjects were enrolled. The prevalence of MS in our study population was 21.7%,
      17.2% and 25.6% for the general population, males and females, respectively. With
      adjustments for age, gender, cigarette smoking, heart rate, total cholesterol,
      low-density lipoprotein (LDL) cholesterol, and the use of anti-hypertensive drug,
      the stepwise regression analysis showed that baPWV had a significant relationship
      with components of MS, including systolic blood pressure (P < 0.001), diastolic
      blood pressure (P < 0.001), glucose (P < 0.001), high-density lipoprotein (HDL)
      cholesterol (P  =  0.04), and triglycerides (P < 0.001), but no relationship with
      waist circumference (P  =  0.25). With an increase in the number of the MS
      components, baPWV increased significantly both in women and men. This study
      indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring
      of baPWV in patients with MS may help in identifying persons at high risk for
      cardiovascular disease. 

PMID- 25050110
TI  - GRP78 inhibits macrophage adhesion via SR-A.
AB  - Class A scavenger receptor (SR-A) plays an important role in macrophage adhesion.
      However, the underlying mechanism remains unclear. We previously found that 78
      kDa glucose-regulated protein (GRP78) inhibited SR-A-mediated ligand
      internalization into macrophage by binding to SR-A. The aim of the study was to
      investigate whether GRP78 could regulate SR-A-mediated cell adhesion. We
      demonstrated that GRP78 bound directly to SR-A by fluorescence resonance energy
      transfer (FRET) assay. Overexpression of GRP78 inhibited macrophage adhesion via
      SR-A. These results suggest that GRP78 may act as an inhibitor of macrophage
      adhesion via SR-A. 

PMID- 25050111
TI  - IRE1alpha knockdown rescues tunicamycin-induced developmental defects and
      apoptosis in Xenopus laevis.
AB  - Inositol requiring enzyme-1 (IRE1) is highly conserved from yeasts to humans.
      Upon endoplasmic reticulum (ER) stress, IRE1 activates X-box-binding protein 1
      (XBP1) by unconventional splicing of XBP1 mRNA, which activates unfolded protein
      response (UPR) to restore ER homeostasis. In mice, IRE1alpha plays an essential
      role in extraembryonic tissues. However, its precise action during the early
      stage of development is unknown. In this study, the gain and loss-of-function
      analyses were used to investigate the function of Xenopus IRE1alpha (xIRE1alpha).
      The effects of xIRE1alpha during embryo development were detected with RT-PCR and
      whole mount in situ hybridization. ER stress was induced by tunicamycin. The
      apoptotic cells were measured by TUNNEL assays. Although both gain and loss of
      xIRE1alpha function had no significant effect on Xenopus embryogenesis, knockdown
      of xIRE1alpha could rescue tunicamycin-induced developmental defects and
      apoptosis. The finding indicates that xIRE1alpha is not required for
      embryogenesis but is required for tunicamycin-induced developmental defects and
      apoptosis in Xenopus laevis. 

PMID- 25050112
TI  - DDX3X regulates cell survival and cell cycle during mouse early embryonic
      development.
AB  - DDX3X is a highly conserved DEAD-box RNA helicase that participates in RNA
      transcription, RNA splicing, and mRNA transport, translation, and nucleo
      cytoplasmic transport. It is highly expressed in metaphase II (MII) oocytes and
      is the predominant DDX3 variant in the ovary and embryo. However, whether it is
      important in mouse early embryo development remains unknown. In this study, we
      investigated the function of DDX3X in early embryogenesis by cytoplasmic
      microinjection with its siRNA in zygotes or single blastomeres of 2-cell embryos.
      Our results showed that knockdown of Ddx3x in zygote cytoplasm led to
      dramatically diminished blastocyst formation, reduced cell numbers, and an
      increase in the number of apoptotic cells in blastocysts. Meanwhile, there was an
      accumulation of p53 in RNAi blastocysts. In addition, the ratio of cell cycle
      arrest during 2-cell to 4-cell transition increased following microinjection of
      Ddx3x siRNA into single blastomeres of 2-cell embryos compared with control.
      These results suggest that Ddx3x is an essential gene associated with cell
      survival and cell cycle control in mouse early embryos, and thus plays key roles
      in normal embryo development. 

PMID- 25050113
TI  - Luteolin prevents uric acid-induced pancreatic beta-cell dysfunction.
AB  - Elevated uric acid causes direct injury to pancreatic beta-cells. In this study,
      we examined the effects of luteolin, an important antioxidant, on uric acid
      induced beta-cell dysfunction. We first evaluated the effect of luteolin on
      nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess
      method. Next, we performed transient transfection and reporter assays to measure
      transcriptional activity of nuclear factor (NF)-kappaB. Western blotting assays
      were also performed to assess the effect of luteolin on the expression of MafA
      and inducible NO synthase (iNOS) in uric acid-treated cells. Finally, we
      evaluated the effect of luteolin on uric acid-induced inhibition of glucose
      stimulated insulin secretion (GSIS) in Min6 cells and freshly isolated mouse
      pancreatic islets. We found that luteolin significantly inhibited uric acid
      induced NO production, which was well correlated with reduced expression of iNOS
      mRNA and protein. Furthermore, decreased activity of NF-kappaB was implicated in
      inhibition by luteolin of increased iNOS expression induced by uric acid.
      Besides, luteolin significantly increased MafA expression in Min6 cells exposed
      to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin
      prevented uric acid-induced inhibition of GSIS in both Min6 cells and mouse
      islets. In conclusion, luteolin protects pancreatic beta-cells from uric acid
      induced dysfunction and may confer benefit on the protection of pancreatic beta
      cells in hyperuricemia-associated diabetes. 

PMID- 25050114
TI  - Schistosoma japonicum infection induces macrophage polarization.
AB  - The role of macrophages (Mphi) as the first line of host defense is well
      accepted. These cells play a central role in orchestrating crucial functions
      during schistosomal infection. Thus, understanding the functional diversity of
      these cells in the process of infection as well as the mechanisms underlying
      these events is crucial for developing disease control strategies. In this study,
      we adopted a Mphi polarization recognition system. M1 macrophage was
      characterized by expressing CD16/32, IL-12 and iNOS. M2 macrophage was
      characterized by expressing CD206, IL-10 and arg-1. In vivo (mouse peritoneal
      macrophages of different infection stages were obtained) and in vitro (different
      S. japonicum antigens were used to stimulate RAW264.7) were characterized by
      using the above mentioned system. NCA and ACA stimulated RAW264.7 express
      significantly higher levels of IL-12 while significantly higher levels of IL-10
      were detected after soluble egg antigen (SEA) stimulation. The results showed
      that dramatic changes of antigen in the microenvironment before and after egg
      production led to macrophage polarization. Furthermore, through TLR blocking
      experiments, the TLR4 signaling pathway was found to play a role in the process
      of macrophage polarization toward M1. Our data suggest that macrophage
      polarization during S. japonicum infection had significant effects on host immune
      responses to S. japonicum. 

PMID- 25050115
TI  - Morphological MRI and T2 mapping of cartilage repair tissue after mosaicplasty
      with tissue-engineered cartilage in a pig model.
AB  - The aim of this study was to evaluate the efficacy of mosaicplasty with tissue
      engineered cartilage for the treatment of osteochondral defects in a pig model
      with advanced MR technique. Eight adolescent miniature pigs were used. The right
      knee underwent mosaicplasty with tissue-engineered cartilage for treatment of
      focal osteochondral defects, while the left knee was repaired via single
      mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue
      was evaluated by magnetic resonance imaging (MRI) with the cartilage repair
      tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26
      weeks were compared with findings of macroscopic and histologic studies. The
      MOCART scores showed that the repaired tissue of the tissue-engineered cartilage
      group was statistically better than that of controls (P < 0.001). A significant
      correlation was found between macroscopic and MOCART scores (P < 0.001).
      Comparable mean T2 values were found between adjacent cartilage and repair tissue
      in the experimental group (P > 0.05). For zonal T2 value evaluation, there were
      no significant zonal T2 differences for repair tissue in controls (P > 0.05). For
      the experimental group, zonal T2 variation was found in repair tissue (P < 0.05).
      MRI, macroscopy and histology showed better repair results and bony incorporation
      in mosaicplasty with the tissue-engineered cartilage group than those of the
      single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a
      promising approach to repair osteochodndral defects. Morphological MRI and T2
      mapping provide a non-invasive method for monitoring the maturation and
      integration of cartilage repair tissue in vivo. 

PMID- 25050116
TI  - Comparing a non-invasive hemodynamic monitor with minimally invasive monitoring
      during major open abdominal surgery.
AB  - As part of the enhanced recovery after surgery (ERAS) protocol, the goal-directed
      fluid management with hemodynamic monitoring can effectively guide perioperative
      fluid use and significantly improve the outcomes in high-risk patients undergoing
      major surgeries. Several minimally invasive and non-invasive monitoring devices
      are commercially available for clinical use. As part of an internal evaluation,
      we reported the results from three different hemodynamic monitoring devices used
      in a patient undergoing a major abdominal surgery. 

PMID- 25050117
TI  - Why is medical education so expensive?

PMID- 25050118
TI  - Evaluation of quantitative variation of secondary metabolites in Bergenia ciliata
      (Haw.) using high performance thin layer chromatography.

PMID- 25050119
TI  - Prevalence and risk factors of asymptomatic colorectal polyps in taiwan.
AB  - Purpose. To investigate the prevalence and risk factors of hyperplastic and
      adenomatous colorectal polyps in a Taiwanese general population. Methods. From
      January 2009 to December 2011, consecutive asymptomatic subjects undergoing a
      routine health check-up were evaluated by colonoscopy. The colorectal polyps were
      assessed, and medical history and demographic data were obtained from each
      patient. Logistic regression analysis was conducted to search the independent
      risk factors for asymptomatic hyperplastic and adenomatous colorectal polyps.
      Results. Of the 1899 asymptomatic subjects, the prevalences of hyperplastic
      polyps and adenomatous polyps were 11.1% and 16.1%, respectively. Multivariate
      analysis revealed that high body mass index (BMI > 25: OR, 1.32, 95% CI, 1.05
      1.71) and current smoking (OR, 1.87, 95% CI, 1.42-2.71) were independent
      predictors for hyperplastic colorectal polyps. Age over 60 years old (OR, 3.49,
      95% CI, 1.86-6.51), high body mass index (BMI > 25: OR, 1.75, 95% CI, 1.21-2.71),
      heavy alcohol consumption (OR, 2.01, 95% CI, 1.02-3.99), and current smoking (OR,
      1.31, 95% CI, 1.04-1.58) were independent predictors for adenomatous colorectal
      polyps. Conclusion. High BMI and smoking are common risk factors for both
      adenomatous and hyperplastic polyps. Old age and alcohol consumption are
      additional risk factors for the development of adenomatous polyps. 

PMID- 25050120
TI  - Influence of the A3669G Glucocorticoid Receptor Gene Polymorphism on the
      Metabolic Profile of Pediatric Patients with Congenital Adrenal Hyperplasia.
AB  - Background. Pediatric CAH patients have an increased risk of cardiovascular
      disease, and it remains unknown if genetic predisposition is a contributing
      factor. Glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an
      adverse metabolic profile. Our aim was to analyze the association between the
      NR3C1 polymorphisms and the metabolic profile of pediatric CAH patients. Methods.
      Forty-one patients (26SW/15SV) received glucocorticoid (GC) replacement therapy
      to achieve normal androgen levels. Obesity was defined by BMI >= 95th percentile.
      NR3C1 alleles were genotyped, and association analyses with phenotype were done
      with Chi-square, t-test, and multivariate and regression analysis. Results.
      Obesity was observed in 31.7% of patients and was not correlated with GC doses
      and treatment duration. Z-score BMI was positively correlated with blood
      pressure, triglycerides, LDL-c levels, and HOMA-IR. NR3C1 polymorphisms, BclI and
      A3669G, were found in 23.1% and 9.7% of alleles, respectively. A3669G carriers
      presented higher LDL-c levels compared to wild-type subjects. BclI-carriers and
      noncarriers did not differ. Conclusion. Our results suggest that A3669G
      polymorphism could be involved with a susceptibility to adverse lipid profile in
      pediatric CAH patients. This study provides new insight into the GR screening
      during CAH treatment, which could help to identify the subgroup of at-risk
      patients who would most benefit from preventive therapeutic action. 

PMID- 25050121
TI  - Osteoporosis, fractures, and diabetes.
AB  - It is well established that osteoporosis and diabetes are prevalent diseases with
      significant associated morbidity and mortality. Patients with diabetes mellitus
      have an increased risk of bone fractures. In type 1 diabetes, the risk is
      increased by ~6 times and is due to low bone mass. Despite increased bone mineral
      density (BMD), in patients with type 2 diabetes the risk is increased (which is
      about twice the risk in the general population) due to the inferior quality of
      bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral
      density, depends on bone quality deterioration rather than bone mass reduction.
      Thus, surrogate markers and examination methods are needed to replace the
      insensitivity of BMD in assessing fracture risks of T2DM patients. One of these
      methods can be trabecular bone score. The aim of the paper is to present the
      present state of scientific knowledge about the osteoporosis risk in diabetic
      patient. The review also discusses the possibility of problematic using the study
      conclusions in real clinical practice. 

PMID- 25050122
TI  - Apical Dimension of Root Canal Clinically Assessed with and without Periapical
      Lesions.
AB  - To clinically evaluate the dimension of the more apical extent of the root canal
      after appropriate preflaring in the case of primary treatment and retreatment
      with and without the presence of periapical radiolucency, 392 single-rooted teeth
      with only one canal were evaluated during endodontic therapy. The canals were
      divided in two groups depending on the presence or absence of periapical
      radiolucency. After preflaring of the root canal the size of the root canal
      terminus (apical canal dimension) was gauged with hand-held Light Speed LS1 files
      inserted at the estimated working length and established with the use of an
      electronic apex locator. The dimension recorded in the computer database was
      represented by the largest instrument able to reach the electronically
      established working length. The differences between the treatment groups were
      assessed using the Mann-Whitney U test and the significance level was set at P <
      0.05. Teeth with lesions had a significantly greater diameter in the apical
      region than teeth without lesions (P < 0.001). The dimension of the apical
      portion of the root canal is larger in the case of periapical radiolucency. This
      involves verifying this parameter in order to use the correct sized instruments
      and to obtain an efficient cutting action at the apical level. 

PMID- 25050124
TI  - Leptospirosis in vellore: a clinical and serological study.
AB  - Leptospirosis is a severe spirochetal zoonosis in the world. It is considered an
      occupational disease of persons engaged in agriculture, sewage works, forestry,
      and animal slaughtering. A study was conducted with an objective of assessing the
      seroprevalence of leptospirosis in and around Vellore district, Tamil Nadu. The
      study was based on the signs and symptoms of the patients reporting fever in
      Vellore Municipal Clinic (Urban Malarial Scheme). Blood samples were collected
      from 129 patients. Animal studies were conducted from 24 rodents captured form
      the market place of the Vellore municipality. In the ZET (Zonal Entomological
      Team, Vellore) Laboratory the sera were examined by macroscopic slide
      agglutination test (MSAT). In the MAST, totally 10 positive leptospiral cases
      from human beings and 10 positive leptospiral cases from rats (Rattus rattus and
      Rattus norvegicus) were found out. Then both positive cases of leptospiral vials
      were labeled, sealed, and sent to the Leptospirosis Research Laboratory,
      Madhavaram, Chennai, for further serovars examination. Among the various serovars
      identified autumnalis was more prevalent. Our findings showed that the age groups
      between 15 and 55 years showed more susceptibility. Particularly the adults were
      more infected. The majority of seropositive individuals in the cases had only
      subclinical infection. Rodents were abundant and contributed to enzootic and
      endemic prevalence of leptospirosis. 

PMID- 25050123
TI  - Thalassemia and hemoglobin e in southern thai blood donors.
AB  - Thalassemia and hemoglobin E (Hb E) are common in Thailand. Individuals with
      thalassemia trait usually have a normal hemoglobin concentration or mild anemia.
      Therefore, thalassemic individuals who have minimum acceptable Hb level may be
      accepted as blood donors. This study was aimed at determining the frequency of
      alpha-thalassemia 1 trait, beta-thalassemia trait, and Hb E-related syndromes in
      Southern Thai blood donors. One hundred and sixteen voluntary blood donors,
      Southern Thailand origin, were recruited for thalassemia and Hb E screening by
      red blood cell indices/dichlorophenolindophenol precipitation test. beta
      Thalassemia and Hb E were then identified by high performance liquid
      chromatography and 4 common alpha-thalassemia deletions were characterized by a
      single tube-multiplex gap-polymerase chain reaction. Overall frequency of
      hemoglobinopathies was 12.9%, classified as follows: homozygous alpha-thalassemia
      2 (1.7%), heterozygous alpha-thalassemia 1 (1.7%), heterozygous beta-thalassemia
      without alpha-thalassemia (0.9%), heterozygous Hb E without alpha-thalassemia
      (5.2%), double heterozygotes for Hb E/alpha-thalassemia 1 (1.7%), homozygous Hb E
      without alpha-thalassemia (0.9%), and homozygous Hb E with heterozygous alpha
      thalassemia 2 (0.9%). The usefulness of thalassemia screening is not only for
      receiving highly effective red blood cells in the recipients but also for
      encouraging the control and prevention program of thalassemia in blood donors. 

PMID- 25050125
TI  - Allergic diseases in subjects under 18 years living with HIV.
AB  - BACKGROUND: In recent decades there has been an increase in the prevalence of
      allergic disease. Manifestations of these diseases have allegedly been observed
      in people living with Human Immunodeficiency Virus (HIV), however, few studies
      have been directed at patients under 18 years old. In this context, the aim of
      this study is to estimate the prevalence of allergic disease in patients under 18
      years old, living with HIV, and to investigate the relationship between clinico
      immunological characteristics of the HIV infection and atopy. METHODS: This is a
      cross-sectional epidemiological study involving patients under 18 years of age
      who were followed up by specialized HIV services in the Southern Region of the
      State of Santa Catarina, Brazil, from February to October 2012. Data collection
      tools included a questionnaire established by the International Study of Asthma
      and Allergy in Childhood (ISAAC), socio-demographic data, as well as laboratory
      test results obtained from the medical records. Blood samples were taken to
      measure total serum Immunoglobulin E (IgE) levels and a Radioallergosorbent Test
      (RAST) for the main aeroallergens. Analysis was performed using Student's t test,
      chi-squared, Fisher's exact and Mann-Whitney tests, wherever indicated, with p <
      0.05 value considered significant. RESULTS: 29 individuals were evaluated. The
      prevalence of symptoms of allergic disease was 65.5% (95% CI 56.1-74.8), the most
      frequent being rhinitis 44.8% (95% CI 35.0-54.5), followed by asthma 37.9% (95%
      CI 28.3-47.4) and eczema 27.6% (95% CI 18.8-36.3). RAST was positive in 20.7% of
      the individuals. There was no significant difference in terms of total serum IgE
      between individuals with and without symptoms of allergic disease. Nevertheless,
      a high frequency of raised levels of total serum IgE (40.7%) and an association
      between raised IgE and clinical staging of disease were observed. A further
      association between CD8+ cell count and prevalence of symptomatic allergic
      disease (p = 0.014) was observed. CONCLUSION: There was a high prevalence of
      reported allergic disease, as well as a high frequency of raised levels of total
      serum IgE. The association between CD8+ cell count and the prevalence of
      symptomatic allergic disease corroborates studies that demonstrated the role of
      such cells in the development of allergic disease.

PMID- 25050126
TI  - Essential oils: new perspectives in human health and wellness.

PMID- 25050127
TI  - The effect of baduanjin on promoting the physical fitness and health of adults.
AB  - The purpose of study was to assess the efficacy of a 16-week Baduanjin qigong
      training intervention in promoting physical fitness and health for adults. An
      experimental design was adopted, and subjects were assigned randomly into an
      experimental group (n = 55) and a control group (n = 55). In the intervention
      group comprised of adults, there were no significant variations in blood glucose,
      blood lipid, blood pressure, heart rate variability, and vital capacity indices.
      The body weight and body mass index (BMI) dropped in the intervention group.
      Compared with the control group, the skinfold thicknesses decreased at lower
      corner of scapula, triceps brachii, and abdomen, with a statistical significance
      (P < 0.001; P = 0.005; P = 0.003). By comparing the physical fitness indices, it
      was found that the increase of the results of sit-and-reach test in the
      intervention group had statistical significance (P = 0.001). In conclusion, it
      was found by our trial that Baduanjin exercise could significantly improve the
      physical flexibility and subcutaneous adipose accumulation in the healthy adults.

PMID- 25050128
TI  - Protective Effect and Mechanism of Total Flavones from Rhododendron simsii Planch
      on Endothelium-Dependent Dilatation and Hyperpolarization in Cerebral Ischemia
      Reperfusion and Correlation to Hydrogen Sulphide Release in Rats.
AB  - We for the first time investigated the effect and mechanism of the total flavones
      of Rhododendron simsii Planch (TFR), a widely-used Chinese herb for a thousand
      years, on vasodilatation and hyperpolarization in middle cerebral artery (MCA) of
      rats subject to global cerebral ischemia-reperfusion (CIR). TFR (11~2700 mg/L)
      evoked dose-dependent vasodilation and hyperpolarization in MCA of both sham and
      CIR that were partially inhibited by 30 MUM N-nitro-L-arginine-methyl-ester and
      10 MUM indomethacin and further attenuated by endogenous H2S synthese-CSE
      inhibitor PPG (100 MUM) or Ca(2+)-activated potassium channel (Kca) inhibitor TEA
      (1 mM). In whole-cell patch clamp recording, TFR remarkably enhanced the outward
      current that was inhibited by TEA. CIR increased CSE mRNA expression and the
      contents of H2S that were further increased by TFR. We conclude that, in MCA of
      CIR rats, TFR induces non-NO and non-PGI2-mediated effects of vasodilatation and
      hyperpolarization involving Kca and increases CSE mRNA expression level in
      endothelial cells and H2S content in the cerebrum. These findings suggest that
      the response induced by TFR is potentially related to endothelium-derived
      hyperpolarizing factor mediated by the endogenous H2S and promote the use of TFR
      in protection of brain from ischemia-reperfusion injury. 

PMID- 25050130
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health.
AB  - Clinical trials, systematic reviews and guidelines compare beneficial and non
      beneficial outcomes following interventions. Often, however, various studies on a
      particular topic do not address the same outcomes, making it difficult to draw
      clinically useful conclusions when a group of studies is looked at as a whole.
      This problem was recently thrown into sharp focus by a systematic review of
      interventions for preterm birth prevention, which found that among 103 randomised
      trials, no fewer than 72 different outcomes were reported. There is a growing
      recognition among clinical researchers that this variability undermines
      consistent synthesis of the evidence, and that what is needed is an agreed
      standardised collection of outcomes - a "core outcomes set" - for all trials in a
      specific clinical area. Recognising that the current inconsistency is a serious
      hindrance to progress in our specialty, the editors of over 50 journals related
      to women's health have come together to support The CROWN (CoRe Outcomes in
      WomeN's health) Initiative. 

PMID- 25050129
TI  - Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of
      Spatial Learning and Memory through Apoptotic Signaling Pathway in the
      Hippocampus of Rats with Abeta 1-40 -Induced Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia and lacks disease
      altering treatments. Fumanjian (FMJ), a famous classic Chinese herbal
      prescription for dementia, was first recorded in the Complete Works of Jingyue
      during the Ming Dynasty. This study aimed to investigate whether FMJ could
      prevent cognitive deficit and take neuroprotective effects in Abeta 1-40-induced
      rat model through apoptotic signaling pathway. AD model was established by
      bilateral injection of Abeta 1-40 into hippocampus in rat. All rats were tested
      for their capabilities of spatial navigation and memorization by Morris water
      maze. Apoptosis was tested using TUNEL staining in hippocampus neuronal cells; RT
      PCR tested expression of Bcl-2 and Bax mRNA; western blotting tested protein
      level of cleaved caspase-3. After 14 days of treatment, FMJ significantly
      improved the escape latency and enhanced platform-cross number compared with the
      Abeta 1-40-injected group (P < 0.05 or P < 0.01). FMJ also significantly
      decreased number of TUNEL-positive neuronal apoptosis and the expressions of Bax
      and cleaved Caspase-3 and increased the expression of Bcl-2 (P < 0.01) compared
      with AD model group. In conclusion, FMJ exerts a protective effect against Abeta
      1-40-induced learning and memory deficits and neuronal apoptosis, suggesting that
      FMJ could be used as a potential therapeutic formula for AD. 

PMID- 25050131
TI  - GrainScan: a low cost, fast method for grain size and colour measurements.
AB  - BACKGROUND: Measuring grain characteristics is an integral component of cereal
      breeding and research into genetic control of seed development. Measures such as
      thousand grain weight are fast, but do not give an indication of variation within
      a sample. Other methods exist for detailed analysis of grain size, but are
      generally costly and very low throughput. Grain colour analysis is generally
      difficult to perform with accuracy, and existing methods are expensive and
      involved. RESULTS: We have developed a software method to measure grain size and
      colour from images captured with consumer level flatbed scanners, in a robust,
      standardised way. The accuracy and precision of the method have been demonstrated
      through screening wheat and Brachypodium distachyon populations for variation in
      size and colour. CONCLUSION: By using GrainScan, cheap and fast measurement of
      grain colour and size will enable plant research programs to gain deeper
      understanding of material, where limited or no information is currently
      available.

PMID- 25050132
TI  - Lumbosacral fixation using sacroiliac buttress screws: a modification to the
      Jackson technique with intrasacral rods.
AB  - BACKGROUND: The use of intrasacral rods has been previously reported for
      posterior lumbosacral fixation. However, problems associated with this technique
      include poor stability of the rod in the sacrum, difficulty in contouring the rod
      to fit the lateral sacral mass, and the complicated assembly procedure for the
      rod and pedicle screws in the thoracolumbar segments after insertion of the rod
      into the sacrum. METHODS: We used a screw with a polyaxial head instead of an
      intrasacral rod, which was inserted into the lateral sacral mass and assembled to
      the rod connected cephalad to pedicle screws. The dorsal side of the screw was
      stabilized by the sacral subchondral bone at the sacroiliac joint with iliac
      buttress coverage, and the tip of the screw was anchored by the sacral cortex.
      RESULTS: Three different cases were used to illustrate lumbosacral fixation using
      intrasacral screws as an anchor for the spinal instrumentation. Effective
      resistance of flexural bending moment and fusion were achieved in these patients
      at the lumbosacral level. CONCLUSIONS: An intrasacral screw can be stabilized by
      subchondral bone with iliac buttress coverage at the dorsal and ventral sacral
      cortex. Posterior spinal fusion with this screw technique enables easier assembly
      of the instrumentation and presents better stabilization than that provided by
      the previously reported intrasacral rod technique for correction and fusion of
      thoracolumbar kyphoscoliosis.

PMID- 25050133
TI  - Predictors of in-hospital mortality and complications in very elderly patients
      undergoing emergency surgery.
AB  - INTRODUCTION: With the increasing aging population demographics and life
      expectancies the number of very elderly patients (age >= 80) undergoing emergency
      surgery is expected to rise. This investigation examines the outcomes in very
      elderly patients undergoing emergency general surgery, including predictors of in
      hospital mortality and morbidity. METHODS: A retrospective study of patients aged
      80 and above undergoing emergency surgery between 2008 and 2010 at a tertiary
      care facility in Canada was conducted. Demographics, comorbidities, surgical
      indications, and perioperative risk assessment data were collected. Outcomes
      included length of hospitalization, discharge destination, and in-hospital
      mortality and morbidity. Multivariable logistic regression was used to identify
      predictors of in-hospital mortality and complications. RESULTS: Of the 170
      patient admissions, the mean age was 84 years and the in-hospital mortality rate
      was 14.7%. Comorbidities were present in 91% of this older patient population.
      Over 60% of the patients required further services or alternate level of care on
      discharge. American Society of Anesthesiologist Physical Status (ASA)
      Classification (OR 5.30, 95% CI 1.774-15.817, p = 0.003) and the development of
      an in-hospital complications (OR 2.51, 95% CI 1.210-5.187, p = 0.013) were
      independent predictors of postoperative mortality. Chronological age or number of
      comorbidities was not predictive of surgical outcome. CONCLUSIONS: Mortality,
      complication rates and post-discharge care requirements were high in very elderly
      patients undergoing emergency general surgery. Advanced age and medical
      comorbidities alone should not be the limiting factors for surgical referral or
      treatment. This study illustrates the importance of preventing an in-hospital
      complication in this very vulnerable population. ASA class is a robust tool which
      is predictive of mortality in the very elderly population and can be used to
      guide patient and family counseling in the emergency setting.

PMID- 25050134
TI  - General peroxidase activity of a parallel G-quadruplex-hemin DNAzyme formed by
      Pu39WT - a mixed G-quadruplex forming sequence in the Bcl-2 P1 promoter.
AB  - BACKGROUND: A 39-base-pair sequence (Pu39WT) located 58 to 19 base pairs upstream
      of the Bcl-2 P1 promoter has been implicated in the formation of an
      intramolecular mixed G-quadruplex structure and is believed to play a major role
      in the regulation of bcl-2 transcription. However, an extensive functional
      exploration requires further investigation. To further exploit the structure
      function relationship of the Pu39WT-hemin DNAzyme, the secondary structure and
      peroxidase activity of the Pu39WT-hemin complex were investigated. RESULTS:
      Experimental results showed that when Pu39WT was incubated with hemin, it formed
      a uniparallel G-quadruplex-hemin complex in K(+) or Na(+) solution, rather than a
      mixed hybrid without bound hemin. Also, Pu39WT-hemin showed peroxidase activity
      (ABTS(2-)) in the presence of H2O2 to produce the colored radical anion (ABTS(*
      )), which could then be used to determine the parameters governing the catalytic
      efficiency and reveal the peroxidase activity of the Pu39WT-hemin DNAzyme.
      CONCLUSIONS: These results demonstrate the general peroxidase activity of Pu39WT
      hemin DNAzyme, which is an intramolecular parallel G-quadruplex structure. This
      peroxidase activity of hemin complexed with the G-quadruplex-forming sequence in
      the Bcl-2 gene promoter may imply a potential mechanism of hemin-mediated
      cellular injury.

PMID- 25050136
TI  - Global mental health and development: a thematic series.

PMID- 25050135
TI  - PHTLS (r) (Prehospital Trauma Life Support) provider courses in Germany - who
      takes part and what do participants think about prehospital trauma care training?
AB  - BACKGROUND: The goal of this study was to examine PHTLS Provider courses in
      Germany and to proof the assumption that formation of physicians and paramedics
      in prehospital trauma care can be optimized. METHODS: PHTLS participants were
      asked to fill out standardized questionnaires during their course preparation and
      directly after the course. There were some open questions regarding their
      professional background and closed questions concerning PHTLS itself. Further
      questions were to be answered on an analog scale in order to quantify subjective
      impressions of confidence, knowledge and also to describe individual levels of
      education and training. RESULTS: 247 questionnaires could be analyzed. Physicians
      noted significant (p < 0.001) more deficits in their professional training than
      paramedics. 80% of the paramedics affirmed to have had adequate training with
      respect to prehospital trauma care, all physicians claimed not to have had
      sufficient training for prehospital trauma care situations at Medical School.
      Physicians were statistically most significant dissatisfied then paramedics (p <
      0.001). While most participants gave positive feedback, anesthetists were less
      convinced of PHTLS (p = 0.005), didn't benefit as much as the rest (p = 0.004)
      and stated more often, that the course was of less value for their daily work (p
      = 0.03). After the course confidence increased remarkably and reached higher
      rates than before the course (p < 0.001). After PHTLS both groups showed similar
      ratings concerning the course concept indicating that PHTLS could equalize some
      training deficits and help to gain confidence and assurance in prehospital trauma
      situations. 90% of the paramedics and 100% of the physicians would recommend
      PHTLS. Physicians and especially anesthetists revised their opinions with regard
      to providing PHTLS at Medical School after having taken part in a PHTLS course.
      CONCLUSION: The evaluation of PHTLS courses in Germany indicates the necessity
      for special prehospital trauma care training. Paramedics and physicians criticize
      deficits in their professional training, which can be compensated by PHTLS. With
      respect to relevant items like confidence and knowledge PHTLS leads to a
      statistically significant increase in ratings on a visual analogue scale. PHTLS
      should be integrated into the curriculum at Medical School.

PMID- 25050137
TI  - A position statement on mental health in the post-2015 development agenda.
AB  - BACKGROUND: The Millennium Development Goals have guided development co-operation
      in the 15 years up to 2015, achieving some significant progress in the priorities
      on which they focused. As the framework for the post-2015 development agenda is
      negotiated, this article reviews the evidence for the place of mental health in
      broader development issues that have already been outlined in the run-up to 2015.
      DISCUSSION: If mental health is going to be recognised as having an essential
      role in development, there needs to be a consensus on priorities for advocacy.
      Various key issues emerged from a survey of stakeholders in the Movement for
      Global Mental Health (MGMH), leading to a Position Statement, which is now
      available for use by advocates. The priorities that emerged were increasing
      access to mental health services, and addressing human rights abuse, stigma, and
      exclusion. SUMMARY: Mental health is a cross-cutting issue, and including it in
      frameworks for action will increase the likelihood of achieving global priorities
      for development such as poverty reduction, economic development, improved health,
      and ensuring the most vulnerable in society are not left behind.

PMID- 25050138
TI  - Improved sugar co-utilisation by encapsulation of a recombinant Saccharomyces
      cerevisiae strain in alginate-chitosan capsules.
AB  - BACKGROUND: Two major hurdles for successful production of second-generation
      bioethanol are the presence of inhibitory compounds in lignocellulosic media, and
      the fact that Saccharomyces cerevisiae cannot naturally utilise pentoses. There
      are recombinant yeast strains that address both of these issues, but co
      utilisation of glucose and xylose is still an issue that needs to be resolved. A
      non-recombinant way to increase yeast tolerance to hydrolysates is by
      encapsulation of the yeast. This can be explained by concentration gradients
      occuring in the cell pellet inside the capsule. In the current study, we
      hypothesised that encapsulation might also lead to improved simultaneous
      utilisation of hexoses and pentoses because of such sugar concentration
      gradients. RESULTS: In silico simulations of encapsulated yeast showed that the
      presence of concentration gradients of inhibitors can explain the improved
      inhibitor tolerance of encapsulated yeast. Simulations also showed pronounced
      concentration gradients of sugars, which resulted in simultaneous xylose and
      glucose consumption and a steady state xylose consumption rate up to 220-fold
      higher than that found in suspension culture. To validate the results
      experimentally, a xylose-utilising S. cerevisiae strain, CEN.PK XXX, was
      constructed and encapsulated in semi-permeable alginate-chitosan liquid core gel
      capsules. In defined media, encapsulation not only increased the tolerance of the
      yeast to inhibitors, but also promoted simultaneous utilisation of glucose and
      xylose. Encapsulation of the yeast resulted in consumption of at least 50% more
      xylose compared with suspended cells over 96-hour fermentations in medium
      containing both sugars. The higher consumption of xylose led to final ethanol
      titres that were approximately 15% higher. In an inhibitory dilute acid spruce
      hydrolysate, freely suspended yeast cells consumed the sugars in a sequential
      manner after a long lag phase, whereas no lag phase was observed for the
      encapsulated yeast, and glucose, mannose, galactose and xylose were utilised in
      parallel from the beginning of the cultivation. CONCLUSIONS: Encapsulation of
      xylose-fermenting S. cerevisiae leads to improved simultaneous and efficient
      utilisation of several sugars, which are utilised sequentially by suspended
      cells. The greatest improvement is obtained in inhibitory media. These findings
      show that encapsulation is a promising option for production of second-generation
      bioethanol.

PMID- 25050139
TI  - A CTNNA3 compound heterozygous deletion implicates a role for alphaT-catenin in
      susceptibility to autism spectrum disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a highly heritable,
      neurodevelopmental condition showing extreme genetic heterogeneity. While it is
      well established that rare genetic variation, both de novo and inherited, plays
      an important role in ASD risk, recent studies also support a rare recessive
      contribution. METHODS: We identified a compound heterozygous deletion
      intersecting the CTNNA3 gene, encoding alphaT-catenin, in a proband with ASD and
      moderate intellectual disability. The deletion breakpoints were mapped at base
      pair resolution, and segregation analysis was performed. We compared the
      frequency of CTNNA3 exonic deletions in 2,147 ASD cases from the Autism Genome
      Project (AGP) study versus the frequency in 6,639 controls. Western blot analysis
      was performed to get a quantitative characterisation of Ctnna3 expression during
      early brain development in mouse. RESULTS: The CTNNA3 compound heterozygous
      deletion includes a coding exon, leading to a putative frameshift and premature
      stop codon. Segregation analysis in the family showed that the unaffected sister
      is heterozygote for the deletion, having only inherited the paternal deletion.
      While the frequency of CTNNA3 exonic deletions is not significantly different
      between ASD cases and controls, no homozygous or compound heterozygous exonic
      deletions were found in a sample of over 6,000 controls. Expression analysis of
      Ctnna3 in the mouse cortex and hippocampus (P0-P90) provided support for its role
      in the early stage of brain development. CONCLUSION: The finding of a rare
      compound heterozygous CTNNA3 exonic deletion segregating with ASD, the absence of
      CTNNA3 homozygous exonic deletions in controls and the high expression of Ctnna3
      in both brain areas analysed implicate CTNNA3 in ASD susceptibility.

PMID- 25050140
TI  - In Vitro Validation of Patient-Specific Hemodynamic Simulations in Coronary
      Aneurysms Caused by Kawasaki Disease.
AB  - To perform experimental validation of computational fluid dynamics (CFD) applied
      to patient specific coronary aneurysm anatomy of Kawasaki disease. We quantified
      hemodynamics in a patient-specific coronary artery aneurysm physical phantom
      under physiologic rest and exercise flow conditions. Using phase contrast MRI
      (PCMRI), we acquired 3-component flow velocity at two slice locations in the
      aneurysms. We then performed numerical simulations with the same geometry and
      inflow conditions, and performed qualitative and quantitative comparisons of
      velocities between experimental measurements and simulation results. We observed
      excellent qualitative agreement in flow pattern features. The quantitative
      spatially and temporally varying differences in velocity between PCMRI and CFD
      were proportional to the flow velocity. As a result, the percent discrepancy
      between simulation and experiment was relatively constant regardless of flow
      velocity variations. Through 1D and 2D quantitative comparisons, we found a 5-17%
      difference between measured and simulated velocities. Additional analysis
      assessed wall shear stress differences between deformable and rigid wall
      simulations. This study demonstrated that CFD produced good qualitative and
      quantitative predictions of velocities in a realistic coronary aneurysm anatomy
      under physiological flow conditions. The results provide insights on factors that
      may influence the level of agreement, and a set of in vitro experimental data
      that can be used by others to compare against CFD simulation results. The
      findings of this study increase confidence in the use of CFD for investigating
      hemodynamics in the specialized anatomy of coronary aneurysms. This provides a
      basis for future hemodynamics studies in patient-specific models of Kawasaki
      disease.

PMID- 25050141
TI  - Alternative medicine for management of breast masses: more harm than good.
AB  - CASE SERIES. PATIENT: -. FINAL DIAGNOSIS: Breast cancer. SYMPTOMS: -. MEDICATION:
      -. CLINICAL PROCEDURE: - SPECIALTY: -. OBJECTIVE: Diagnostic/therapeutic
      accidents. BACKGROUND: Several well-established, evidence-based treatment
      modalities are currently available and widely applied to breast cancer patients,
      but it is known that some of the cancer patients use traditional/alternative
      medicine other than their treatments. CASE REPORT: Herein, we report the cases of
      2 middle-aged women (45 and 50 years old) with malignant breast masses who
      experienced serious complications in response to self-prescribed use of
      alternative medicine practices to treat their condition in lieu of evidence-based
      medical treatment. Specifically, the use and/or inappropriate application of
      alternative medical approaches promoted the progression of malignant fungating
      lesions in the breast for these 2 patients. The first patient sought medical
      assistance upon development of a fungating lesion 7~8 cm in diameter and
      involving 1/3 of the breast, with a palpable mass of 5*6 cm immediately beneath
      the wound. The second patient sought medical assistance upon development of a
      wide, bleeding, ulcerous area with patchy necrotic tissue that comprised 2/3 of
      the breast and had a 10*6 cm palpable mass under the affected area. Use of some
      non-evidence-based medical treatments as complementary to evidence-based medical
      treatments may benefit the patient on an emotional level; however, this strategy
      should be used with caution, as the non-evidence-based therapies may cause
      physical harm or even counteract the evidence-based treatment. CONCLUSIONS: A
      malignant, fungating wound is a serious complication of advanced breast cancer.
      It is critical that the public is informed about the potential problems of self
      treating wounds such as breast ulcers and masses. Additionally, campaigns are
      needed to increase awareness of the risks and life-threatening potential of using
      non-evidence-based medical therapies exclusively.

PMID- 25050143
TI  - Aronia melanocarpa Elliot reduces the activity of angiotensin i-converting enzyme
      in vitro and ex vivo studies.
AB  - PURPOSE: The aim of the study was to analyze the effects of two-month
      supplementation with chokeberry preparation on the activity of angiotensin I
      converting enzyme (ACE) in patients with metabolic syndrome (MS). During the in
      vitro stage of the study, we determined the concentration of chokeberry extract,
      which inhibited the activity of ACE by 50% (IC50). METHODS: The participants (n =
      70) were divided into three groups: I-patients with MS who received chokeberry
      extract supplements, II-healthy controls, and III-patients with MS treated with
      ACE inhibitors. RESULTS: After one and two months of the experiment, a decrease
      in ACE activity corresponded to 25% and 30%, respectively. We documented
      significant positive correlations between the ACE activity and the systolic (r =
      0.459, P = 0.048) and diastolic blood pressure, (r = 0.603, P = 0.005) and CRP.
      The IC50 of chokeberry extract and captopril amounted to 155.4 +/- 12.1 MUg/mL
      and 0.52 +/- 0.18 MUg/mL, respectively. CONCLUSIONS: Our in vitro study revealed
      that chokeberry extract is a relatively weak ACE inhibitor. However, the results
      of clinical observations suggest that the favorable hypotensive action of
      chokeberry polyphenols may be an outcome of both ACE inhibition and other
      pleotropic effects, for example, antioxidative effect.

PMID- 25050145
TI  - Current opinions on surgical treatment of fractures of the condylar head.
AB  - Treatment of mandibular condyle fractures is still controversial, with surgical
      treatment slowly becoming the preferred option. However, fractures of the
      condylar head (diacapitular fractures) are still treated conservatively at many
      institutions. Recently, more and more surgeons have begun to perform open
      treatment for diacapitular fractures because it allows to restore the anatomical
      position of the fragments and disc, it allows an immediate functional movement of
      the jaw, and avoid the ankylosis of the temporomandibular joint induced by the
      trauma. Several techniques have been proposed to reduce and fix fractures of the
      condylar head, such as standard bone screws, resorbable screws, resorbable pins,
      and cannulated lag screws. Therefore, the aim of this article is to review the
      literature about the surgical treatment of fractures of the condylar head to
      resume the current knowledge about open treatment of such fractures. 

PMID- 25050142
TI  - Signaling mechanisms and disrupted cytoskeleton in the diphenyl ditelluride
      neurotoxicity.
AB  - Evidence from our group supports that diphenyl ditelluride (PhTe)2 neurotoxicity
      depends on modulation of signaling pathways initiated at the plasma membrane. The
      (PhTe)2-evoked signal is transduced downstream of voltage-dependent Ca(2+)
      channels (VDCC), N-methyl-D-aspartate receptors (NMDA), or metabotropic glutamate
      receptors activation via different kinase pathways (protein kinase A,
      phospholipase C/protein kinase C, mitogen-activated protein kinases (MAPKs), and
      Akt signaling pathway). Among the most relevant cues of misregulated signaling
      mechanisms evoked by (PhTe)2 is the cytoskeleton of neural cells. The in vivo and
      in vitro exposure to (PhTe)2 induce hyperphosphorylation/hypophosphorylation of
      neuronal and glial intermediate filament (IF) proteins (neurofilaments and glial
      fibrillary acidic protein, resp.) in different brain structures of young rats.
      Phosphorylation of IFs at specific sites modulates their
      association/disassociation and interferes with important physiological roles,
      such as axonal transport. Disrupted cytoskeleton is a crucial marker of
      neurodegeneration and is associated with reactive astrogliosis and apoptotic cell
      death. This review focuses the current knowledge and important results on the
      mechanisms of (PhTe)2 neurotoxicity with special emphasis on the cytoskeletal
      proteins and their differential regulation by kinases/phosphatases and Ca(2+)
      mediated mechanisms in developmental rat brain. We propose that the disrupted
      cytoskeletal homeostasis could support brain damage provoked by this
      neurotoxicant. 

PMID- 25050144
TI  - Bach1 deficiency and accompanying overexpression of heme oxygenase-1 do not
      influence aging or tumorigenesis in mice.
AB  - Oxidative stress contributes to both aging and tumorigenesis. The transcription
      factor Bach1, a regulator of oxidative stress response, augments oxidative stress
      by repressing the expression of heme oxygenase-1 (HO-1) gene (Hmox1) and
      suppresses oxidative stress-induced cellular senescence by restricting the p53
      transcriptional activity. Here we investigated the lifelong effects of Bach1
      deficiency on mice. Bach1-deficient mice showed longevity similar to wild-type
      mice. Although HO-1 was upregulated in the cells of Bach1-deficient animals, the
      levels of ROS in Bach1-deficient HSCs were comparable to those in wild-type
      cells. Bach1(-/-); p53(-/-) mice succumbed to spontaneous cancers as frequently
      as p53-deficient mice. Bach1 deficiency significantly altered transcriptome in
      the liver of the young mice, which surprisingly became similar to that of wild
      type mice during the course of aging. The transcriptome adaptation to Bach1
      deficiency may reflect how oxidative stress response is tuned upon genetic and
      environmental perturbations. We concluded that Bach1 deficiency and accompanying
      overexpression of HO-1 did not influence aging or p53 deficiency-driven
      tumorigenesis. Our results suggest that it is useful to target Bach1 for acute
      injury responses without inducing any apparent deteriorative effect.

PMID- 25050146
TI  - Application of digital anthropometry for craniofacial assessment.
AB  - Craniofacial anthropometry is an objective technique based on a series of
      measurements and proportions, which facilitate the characterization of phenotypic
      variation and quantification of dysmorphology. With the introduction of
      stereophotography, it is possible to acquire a lifelike three-dimensional (3D)
      image of the face with natural color and texture. Most of the traditional
      anthropometric landmarks can be identified on these 3D photographs using
      specialized software. Therefore, it has become possible to compute new digital
      measurements, which were not feasible with traditional instruments. The term
      "digital anthropometry" has been used by researchers based on such systems to
      separate their methods from conventional manual measurements. Anthropometry has
      been traditionally used as a research tool. With the advent of digital
      anthropometry, this technique can be employed in several disciplines as a
      noninvasive tool for quantifying facial morphology. The aim of this review is to
      provide a broad overview of digital anthropometry and discuss its clinical
      applications. 

PMID- 25050147
TI  - Evaluation of 2.0-mm Titanium Three-Dimensional Curved Angle Strut Plate in the
      Fixation of Mandibular Angle Fractures-A Prospective Clinical and Radiological
      Analysis.
AB  - The aim of the study was to evaluate the efficacy and complication rate with use
      of 2.0-mm titanium three-dimensional (3D) curved angle strut plate for mandibular
      angle fractures. Twenty cases requiring internal fixation of the mandibular angle
      by 2.0-mm titanium 3D curved angle strut plates were evaluated. Postoperative
      clinical and radiological analyses were done on 1st, 2nd, 4th, and 6th weeks,
      which included wound healing, transmitted movements, difficulty in function and
      occlusion, and neurosensory changes, if any. Reasonable level of success in terms
      of immediate jaw function was noted in all cases. Transient inferior alveolar
      nerve dysfunction was observed in three cases, which recovered gradually in 2
      months, and surgical site infection was observed in two cases, which resolved
      with appropriate course of antibiotics and wound care. Fixation of mandibular
      angle fractures with a 2.0-mm titanium 3D curved angle strut plate is
      predictable, expeditious, and has less complication rate. 

PMID- 25050148
TI  - Two stage enucleation and deflation of a large unicystic ameloblastoma with mural
      invasion in mandible.
AB  - A treatment for strategy of unicystic ameloblastoma (UA) should be decided by its
      pathology type including luminal or mural type. Luminal type of UA can be treated
      only by enucleation alone, but UA with mural invasion should be treated
      aggressively like conventional ameloblastomas. However, it is difficult to
      diagnose the subtype of UA by an initial biopsy. There is a possibility that the
      lesion is an ordinary cyst or keratocystic odontogenic tumor, leading to a
      possible overtreatment. Therefore, this study performed the enucleation of the
      cyst wall and deflation at first, and the pathological finding confirmed mural
      invasion into the cystic wall, leading to the second surgery. The second surgery
      enucleated scar tissue, bone curettage, and deflation, and was able to contribute
      to the reduction of the recurrence rate by removing tumor nest in scar tissue or
      new bone, enhancing new bone formation, and shrinking the mandibular expanding by
      fenestration. In this study, a large UA with mural invasion including condyle was
      treated by "two-stage enucleation and deflation" in a 20-year-old patient. 

PMID- 25050149
TI  - Rapid prototyping technology in orbital floor reconstruction: application in
      three patients.
AB  - Rapid prototyping entails the fabrication of three-dimensional anatomical models
      which provide an accurate and cost-effective method to visualize complex
      anatomical structures. Our unit has been using this to assist in the diagnosis,
      planning, and preoperative titanium plate adaptation for orbital reconstruction
      surgery following traumatic injury. The aim of this article is to demonstrate the
      potential clinical and cost-saving benefits of this technology. 

PMID- 25050150
TI  - Extraction of Fronto-orbital Shower Hook through Transcranial Orbitotomy.
AB  - Transorbital foreign bodies threaten both the integrity of the globe and the
      brain. We present an unusual case of a penetrating right frontal lobe-orbital
      metallic shower hook. Extensive intracranial involvement necessitated
      transcranial orbitotomy allowing for the removal of the object without loss of
      the globe. 

PMID- 25050152
TI  - Erratum: nasofrontal outflow tract visibility in computed tomography imaging of
      frontal sinus fractures.

PMID- 25050151
TI  - Bilateral alloplastic prostheses for temporomandibular joint reconstruction in a
      patient with ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) or Bechterew disease is a chronic, usually
      progressive, systemic inflammatory joint disease, which predominantly affects the
      spine and sacroiliac joints. In these joints, early inflammatory changes are
      followed by lumbosacral pain and progressive restriction of spinal movement
      associated with radiologically visible intervertebral ossification. Peripheral
      joint involvement occurs in 10 to 30% of patients and shows a predilection for
      the shoulders, knees, ankles, feet, and wrists. Temporomandibular joint (TMJ)
      involvement has been described, and its reported frequency varies from 11 to 35%.
      However, ankylosis is uncommon with a single documented case utilizing an
      alloplastic prosthesis for total joint replacement. A case report of bilateral
      ankylosis of the jaw treated with alloplastic prostheses for total TMJ
      replacement using a Brazilian system in a patient with AS is presented. 

PMID- 25050153
TI  - Drug discovery research in India: current state and future prospects.
AB  - Indian civilization developed a strong system of traditional medicine and was one
      of the first nations to develop a synthetic drug. In the postindependence era,
      Indian pharmaceutical industry developed a strong base for production of generic
      drugs. Challenges for the future are to give its traditional medicine a strong
      scientific base and develop research and clinical capability to consistently
      produce new drugs based on advances in modern biological sciences. 

PMID- 25050154
TI  - Protein-ligand cocrystal structures: we can do better.
AB  - There is a large body of evidence that many protein-ligand cocrystal structures
      contain poorly refined ligand geometries. These errors result in bound structures
      that have nonideal bond lengths and angles, are strained, contain improbable
      conformations, and have bad protein-ligand contacts. Many of these problems can
      be greatly reduced with better refinement models. 

PMID- 25050155
TI  - Pim kinase inhibitors for the treatment of cancer and possibly more.

PMID- 25050156
TI  - Inhibition of the Bacterial Adhesin FimH May Potentially Treat Inflammatory Bowel
      Diseases (IBD).

PMID- 25050157
TI  - LPM7 Inhibitors May Potentially Treat Autoimmune Diseases.

PMID- 25050158
TI  - Discovery of a Negative Allosteric Modulator of GABAB Receptors.
AB  - Initialized from the scaffold of CGP7930, an allosteric agonist of GABAB
      receptors, a series of noncompetitive antagonists were discovered. Among these
      compounds, compounds 3, 6, and 14 decreased agonist GABA-induced maximal effect
      of IP3 production in HEK293 cells overexpressing GABAB receptors and Gqi9
      proteins without changing the EC50. Compounds 3, 6, and 14 not only inhibited
      agonist baclofen-induced ERK1/2 phosphorylation but also blocked CGP7930-induced
      ERK1/2 phosphorylation in HEK293 cells overexpressing GABAB receptors. The
      results suggested that compounds 3, 6, and 14 are negative allosteric modulators
      of GABAB receptors. The representative compound 14 decreased GABA-induced IP3
      production with IC50 of 37.9 MUM and had no effect on other GPCR Class C members
      such as mGluR1, mGluR2, and mGluR5. Finally, we showed that compound 14 did not
      bind to the orthosteric binding sites of GABAB receptors, demonstrating that
      compound 14 negatively modulated GABAB receptors activity as a negative
      allosteric modulator. 

PMID- 25050159
TI  - Investigation of Cardiovascular Effects of Tetrahydro-beta-carboline sstr3
      antagonists.
AB  - Antagonism of somatostatin subtype receptor 3 (sstr3) has emerged as a potential
      treatment of Type 2 diabetes. Unfortunately, the development of our first
      preclinical candidate, MK-4256, was discontinued due to a dose-dependent QTc (QT
      interval corrected for heart rate) prolongation observed in a conscious
      cardiovascular (CV) dog model. As the fate of the entire program rested on
      resolving this issue, it was imperative to determine whether the observed QTc
      prolongation was associated with hERG channel (the protein encoded by the human
      Ether-a-go-go-Related Gene) binding or was mechanism-based as a result of
      antagonizing sstr3. We investigated a structural series containing carboxylic
      acids to reduce the putative hERG off-target activity. A key tool compound, 3A,
      was identified from this SAR effort. As a potent sstr3 antagonist, 3A was shown
      to reduce glucose excursion in a mouse oGTT assay. Consistent with its minimal
      hERG activity from in vitro assays, 3A elicited little to no effect in an
      anesthetized, vagus-intact CV dog model at high plasma drug levels. These results
      afforded the critical conclusion that sstr3 antagonism is not responsible for the
      QTc effects and therefore cleared a path for the program to progress. 

PMID- 25050160
TI  - Small Molecule that Reverses Dexamethasone Resistance in T-cell Acute
      Lymphoblastic Leukemia (T-ALL).
AB  - Glucocorticoids are one of the most utilized and effective therapies in treating
      T-cell acute lymphoblastic leukemia. However, patients often develop resistance
      to glucocorticoids, rendering these therapies ineffective. We screened 9517
      compounds, selected for their lead-like properties, chosen from among 3 372 615
      compounds, against a dexamethasone-resistant T-ALL cell line to identify small
      molecules that reverse glucocorticoid resistance. We synthesized analogues of the
      most effective compound, termed J9, from the screen in order to define the
      scaffold's structure-activity relationship. Active compounds restored sensitivity
      to glucocorticoids through upregulation of the glucocorticoid receptor. This
      compound and mechanism may provide a strategy for overcoming glucocorticoid
      resistance in patients with T-ALL. 

PMID- 25050161
TI  - Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple
      reuptake inhibitors.
AB  - A series of 4-bicyclic heteroaryl 1,2,3,4-tetrahydroisoquinoline inhibitors of
      the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine
      transporter (DAT) was discovered. The synthesis and structure-activity
      relationship (SAR) of these triple reuptake inhibitors (TRIs) will be discussed.
      Compound 10i (AMR-2), a very potent inhibitor of SERT, NET, and DAT, showed
      efficacy in the rat forced-swim and mouse tail suspension models with minimum
      effective doses of 0.3 and 1 mg/kg (po), respectively. At efficacious doses in
      these assays, 10i exhibited substantial occupancy levels at the three
      transporters in both rat and mouse brain. The study of the metabolism of 10i
      revealed the formation of a significant active metabolite, compound 13. 

PMID- 25050162
TI  - Synthesis and Pharmacological Evaluation of DHbetaE Analogues as Neuronal
      Nicotinic Acetylcholine Receptor Antagonists.
AB  - Dihydro-beta-erythroidine (DHbetaE) is a member of the Erythrina family of
      alkaloids and a potent competitive antagonist of the alpha4beta2-subtype of the
      nicotinic acetylcholine receptors (nAChRs). Guided by an X-ray structure of
      DHbetaE in complex with an ACh binding protein, we detail the design, synthesis,
      and pharmacological characterization of a series of DHbetaE analogues in which
      two of the four rings in the natural product has been excluded. We found that the
      direct analogue of DHbetaE maintains affinity for the alpha4beta2-subtype, but
      further modifications of the simplified analogues were detrimental to their
      activities on the nAChRs. 

PMID- 25050163
TI  - Chemically accessible hsp90 inhibitor that does not induce a heat shock response.
AB  - Recent cancer therapies have focused on targeting biology networks through a
      single regulatory protein. Heat shock protein 90 (hsp90) is an ideal oncogenic
      target as it regulates over 400 client proteins and cochaperones. However,
      clinical inhibitors of hsp90 have had limited success; the primary reason being
      that they induce a heat shock response. We describe the synthesis and biological
      evaluation of a new hsp90 inhibitor, SM253. The previous generation on which
      SM253 is based (SM145) has poor overall synthetic yields, low solubility, and
      micromolar cytotoxicity. By comparison SM253 has relatively high overall yields,
      good aqueous solubility, and is more cytotoxic than its parent compound.
      Verification that hsp90 is SM253's target was accomplished using pull-down and
      protein folding assays. SM253 is superior to both SM145 and the clinical
      candidate 17-AAG as it decreases proteins related to the heat shock response by 2
      fold, versus a 2-4-fold increase observed when cells are treated with 17-AAG. 

PMID- 25050164
TI  - Bioreductively Activated Reactive Oxygen Species (ROS) Generators as MRSA
      Inhibitors.
AB  - The number of cases of drug resistant Staphylococcus aureus infections is on the
      rise globally and new strategies to identify drug candidates with novel
      mechanisms of action are in urgent need. Here, we report the synthesis and
      evaluation of a series of benzo[b]phenanthridine-5,7,12(6H)-triones, which were
      designed based on redox-active natural products. We find that the in vitro
      inhibitory activity of 6-(prop-2-ynyl)benzo[b]phenanthridine-5,7,12(6H)-trione
      (1f) against methicillin-resistant Staphylococcus aureus (MRSA), including a
      panel of patient-derived strains, is comparable or better than vancomycin. We
      show that the lead compound generates reactive oxygen species (ROS) in the cell,
      contributing to its antibacterial activity. 

PMID- 25050165
TI  - Novel FTY720-Based Compounds Stimulate Neurotrophin Expression and Phosphatase
      Activity in Dopaminergic Cells.
AB  - alpha-Synuclein is a chaperone-like protein implicated in Parkinson's disease
      (PD). Among alpha-synuclein's normal functions is an ability to bind to and
      stimulate the activity of the protein phosphatase 2A (PP2A) catalytic subunit in
      vitro and in vivo. PP2A activity is impaired in PD and in dementia with Lewy
      Bodies in brain regions harboring alpha-synuclein aggregates. Using PP2A as the
      readout, we measured PP2A activity in response to alpha-synuclein, ceramides, and
      FTY720, and then on the basis of those results, we created new FTY720 compounds.
      We then measured the effects of those compounds in dopaminergic cells. In
      addition to stimulating PP2A, all three compounds stimulated the expression of
      brain derived neurotrophic factor and protected MN9D cells against tumor-necrosis
      factor-alpha-associated cell death. FTY720-C2 appears to be more potent while
      FTY720-Mitoxy targets mitochondria. Importantly, FTY720 is already FDA approved
      for treating multiple sclerosis and is used clinically worldwide. Our findings
      suggest that FTY720 and our new FTY720-based compounds have considerable
      potential for treating synucleinopathies such as PD. 

PMID- 25050167
TI  - Carbonic anhydrase inhibitors: design, synthesis, and biological evaluation of
      novel sulfonyl semicarbazide derivatives.
AB  - A series of novel sulfonyl semicarbazides 5-13 was designed, synthesized, and
      evaluated for human carbonic anhydrase (hCA) inhibition. The new sulfonyl
      semicarbazides were tested against a panel of hCA isoforms I, II, IX, and XII,
      using acetazolamide (AZA, 1) as standard. All the sulfonyl semicarbazides showed
      subnanomolar affinity for hCA XII (pK i range 0.59-0.79 nM) and high selectivity
      over hCA I (58-114-fold) and hCA IX (26-114-fold) compared to hCA II (5-20-fold
      except 11, 121-fold). The importance of the nature of para-substitution on the
      sulfonyl substituted aromatic ring for potency and selectivity against one hCA
      isoform versus others is discussed. Overall, the research work led to the
      development of highly potent and selective hCA inhibitors. 

PMID- 25050166
TI  - Structure-based design of substituted piperidines as a new class of highly
      efficacious oral direct Renin inhibitors.
AB  - A cis-configured 3,5-disubstituted piperidine direct renin inhibitor, (syn,rac)
      1, was discovered as a high-throughput screening hit from a target-family
      tailored library. Optimization of both the prime and the nonprime site residues
      flanking the central piperidine transition-state surrogate resulted in analogues
      with improved potency and pharmacokinetic (PK) properties, culminating in the
      identification of the 4-hydroxy-3,5-substituted piperidine 31. This compound
      showed high in vitro potency toward human renin with excellent off-target
      selectivity, 60% oral bioavailability in rat, and dose-dependent blood pressure
      lowering effects in the double-transgenic rat model. 

PMID- 25050168
TI  - Novel hybrids of natural oridonin-bearing nitrogen mustards as potential
      anticancer drug candidates.
AB  - A series of novel hybrids from natural product oridonin and nitrogen mustards
      were designed and synthesized to obtain more efficacious and less toxic antitumor
      agents. The antiproliferative evaluation showed that most conjugates were more
      potent than their parent compounds oridonin and clinically used nitrogen mustards
      against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803).
      Furthermore, the representative compounds 16a-c exhibited antiproliferative
      activities against the multidrug resistant cell lines (SW620/AD300 and NCI
      H460/MX20). It was shown that the most effective compound 16b possesses a strong
      inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF
      7 cells and also exhibits selective cytotoxicity toward the cancer cells.
      Intriguingly, compound 16b has been demonstrated to significantly induce
      apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells. 

PMID- 25050169
TI  - Optimization of 1,2,4-Triazolopyridines as Inhibitors of Human 11beta
      Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD-1).
AB  - Small alkyl groups and spirocyclic-aromatic rings directly attached to the left
      side and right side of the 1,2,4-triazolopyridines (TZP), respectively, were
      found to be potent and selective inhibitors of human 11beta-hydroxysteroid
      dehydrogenase-type 1 (11beta-HSD-1) enzyme. 3-(1-(4-Chlorophenyl)cyclopropyl)-8
      cyclopropyl-[1,2,4]triazolo[4,3-a]pyridine (9f) was identified as a potent
      inhibitor of the 11beta-HSD-1 enzyme with reduced Pregnane-X receptor (PXR)
      transactivation activity. The binding orientation of this TZP series was revealed
      by X-ray crystallography structure studies. 

PMID- 25050170
TI  - Enhanced Cytotoxicity through Conjugation of a "Clickable" Luminescent Re(I)
      Complex to a Cell-Penetrating Lipopeptide.
AB  - Re(I) tricarbonyl polypyridine-based complexes are particularly attractive metal
      complexes in the field of inorganic chemical biology due to their luminescent
      properties, ease of conjugation to targeting biomolecules, and the possibility to
      prepare their "hot" (99m)Tc analogues for radioimaging. In this study, we
      prepared and characterized a novel, "clickable" complex, [Re(2,2'-bipyridine)(3
      ethynylpyridine)(CO)3](BF4) ([Re(CO) 3 (bipy)(py-alkyne)](BF 4 )), exhibiting the
      characteristic luminescent properties and moderate cytotoxicity of this general
      class of compound. Using Cu(I)-catalyzed "click" chemistry, the complex was
      efficiently attached to a lipidated peptide known to increase cell permeability,
      namely, the myristoylated HIV-1 Tat peptide (myr-Tat), to give Re-myr-Tat.
      Fluorescence microscopy localization in human cervical cancer cells (HeLa)
      confirmed enhanced cellular uptake of Re-myr-Tat compared with [Re(CO) 3
      (bipy)(py-alkyne)](BF 4 ), and cytotoxicity studies showed that this resulted in
      an increase in potency to a level comparable with cisplatin (13.0 +/- 2.0 MUM). 

PMID- 25050171
TI  - Two Potent OXE-R Antagonists: Assignment of Stereochemistry.
AB  - 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is formed by the oxidation of 5
      hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), which is a major metabolite
      of enzymatic oxidation of arachidonic acid (AA). 5-Oxo-ETE is the most potent
      lipid chemoattractant for human eosinophils. Its actions are mediated by the
      selective OXE receptor, which is therefore an attractive target in eosinophilic
      diseases such as allergic rhinitis and asthma. Recently, we have reported two
      excellent OXE receptor antagonists that have IC50 values at low nanomolar
      concentrations. Each of these antagonists has a chiral center, and the isolation
      of the individual enantiomers by chiral high-performance liquid chromatography
      (HPLC) revealed that in each case one enantiomer is over 300 times more potent
      than the other. To unambiguously assign the stereochemistry of these enantiomers
      and to provide access to larger amounts of the active compounds for biological
      testing, we report here their total synthesis. 

PMID- 25050172
TI  - Benzimidazoles: novel mycobacterial gyrase inhibitors from scaffold morphing.
AB  - Type II topoisomerases are well conserved across the bacterial species, and
      inhibition of DNA gyrase by fluoroquinolones has provided an attractive option
      for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone
      resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its
      sustainability. A scaffold hopping approach using the binding mode of novel
      bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel
      class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity.
      Docking of benzimidazoles to a NBTI bound crystal structure suggested that this
      class of compound makes key contacts in the enzyme active site similar to the
      reported NBTIs. This observation was further confirmed through the measurement of
      DNA gyrase inhibition, and activity against Mtb strains harboring mutations that
      confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to
      moxifloxacin. Structure-activity relationship modification at the C-7 position of
      the left-hand side ring provided further avenue to improve hERG selectivity for
      this chemical series that has been the major challenges for NBTIs. 

PMID- 25050173
TI  - Sulfonamides with Potent Inhibitory Action and Selectivity against the alpha
      Carbonic Anhydrase from Vibrio cholerae.
AB  - By using N-alpha-acetyl-l-lysine or GABA scaffolds and the conversion of the
      terminal amino group to the guanidine one, benzenesulfonamides incorporating
      water solubilizing moieties were synthesized. The new compounds were medium
      potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms
      I and II, and highly effective, nanomolar inhibitors of the pathogenic bacterial
      alpha-CA from Vibrio cholerae. These sulfonamides possess good selectivity for
      inhibiting the bacterial over the mammalian isoforms and may be used as tools to
      understand the role of bacterial CAs in pathogenesis. 

PMID- 25050174
TI  - Azapropellanes with anti-influenza a virus activity.
AB  - The synthesis of several [4,4,3], [4,3,3], and [3,3,3]azapropellanes is reported.
      Several of the novel amines displayed low-micromolar activities against an
      amantadine-resistant H1N1 strain, but they did not show activity against an
      amantadine-sensitive H3N2 strain. None of the tested compounds inhibit the
      influenza A/M2 proton channel function. Most of the compounds did not show
      cytotoxicity for MDCK cells. 

PMID- 25050175
TI  - Clinical significance of epithelial-mesenchymal transition.
AB  - The concept of epithelial-mesenchymal transition (EMT), a process where cells
      change their epithelial towards a mesenchymal phenotype, has gained overwhelming
      attention especially in the cancer research community. Thousands of scientific
      reports investigated changes in gene, mRNA and protein expression compatible with
      EMT and their possible correlation with tumor invasion, metastatic spread or
      patient prognosis; however, up to now, a proof of clinical significance of the
      concept is still missing. This review, with a main focus on the role of EMT in
      tumors, will summarize the basic molecular events underlying EMT including the
      signaling pathways capable of its induction as well as changes in EMT-associated
      protein expression and will very briefly touch the role of microRNAs in EMT. We
      then outline protein markers that are used most frequently for the assessment of
      EMT in research and diagnostic evaluation of tumor specimens and depict the link
      between EMT, a cancer stem cell (CSC) phenotype and resistance to conventional
      antineoplastic therapies. Furthermore, we evaluate a possible correlation between
      EMT marker expression and patient prognosis as well as current therapeutic
      concepts targeting the EMT process to slow down or prevent metastatic spread of
      malignant tumors. 

PMID- 25050176
TI  - Bronchial asthma and chronic obstructive pulmonary disease: research activity in
      Arab countries.
AB  - BACKGROUND: Chronic respiratory diseases, like bronchial asthma and chronic
      obstructive pulmonary disease (COPD), are a worldwide health problem.
      Quantitative and qualitative assessment of asthma and COPD-related research from
      Arab countries has not been explored and there are few internationally published
      reports on such field. The main objectives of this study were to analyze research
      output originating from Arab countries in the field of bronchial asthma and COPD.
      METHODS: Original scientific articles or reviews published from the 22 Arab
      countries were screened using specific words pertaining to asthma and COPD using
      Scopus database and search engine. Research productivity was evaluated based on:
      (a) total and trends of contribution of each Arab country to asthma and COPD
      research and (b) journals in which researchers from Arab countries published
      their research. RESULTS: The total number of original research and review
      articles published globally about bronchial asthma and COPD was 163,964. The
      leading country in bronchial asthma and COPD research was United States of
      America (38,632; 23.56%). Worldwide, Turkey ranked 19th while Israel and Iran
      ranked 25th and 29th respectively. Among Arab countries, Egypt and Kingdom of
      Saudi Arabia came on positions 39th and 43rd, respectively. A total of 1,304
      documents about bronchial asthma and COPD were published from Arab countries
      which represents 0.8% of the global research output. Research in bronchial asthma
      was almost double that in COPD. Research from Arab countries was low and showed a
      significant increase after 2000. Approximately 12% of research activity in asthma
      and COPD from Arab countries was published in Saudi Medical Journal, Annals of
      Saudi Medicine, Eastern Mediterranean Health Journal and Tunisie Medicale.
      Kingdom of Saudi Arabia, with a total publication of 353 (27.07%) ranked first
      among the Arab countries while University of Kuwait was the most productive
      institution with a total of 123 (9.43%) documents. CONCLUSIONS: The present data
      showed relatively low research productivity about bronchial asthma and COPD in
      Arab countries. Research output can be improved by investing more in
      international and national collaborative research projects in the field of asthma
      and COPD.

PMID- 25050177
TI  - Emotional Regulation and Depression: A Potential Mediator between Heart and Mind.
AB  - A narrative review of the major evidence concerning the relationship between
      emotional regulation and depression was conducted. The literature demonstrates a
      mediating role of emotional regulation in the development of depression and
      physical illness. Literature suggests in fact that the employment of adaptive
      emotional regulation strategies (e.g., reappraisal) causes a reduction of stress
      elicited emotions leading to physical disorders. Conversely, dysfunctional
      emotional regulation strategies and, in particular, rumination and emotion
      suppression appear to be influential in the pathogenesis of depression and
      physiological disease. More specifically, the evidence suggests that depression
      and rumination affect both cognitive (e.g., impaired ability to process negative
      information) and neurobiological mechanisms (e.g., hypothalamic pituitary adrenal
      axis overactivation and higher rates of cortisol production). Understanding the
      factors that govern the variety of health outcomes that different people
      experience following exposure to stress has important implications for the
      development of effective emotion-regulation interventional approaches (e.g.,
      mindfulness-based therapy, emotion-focused therapy, and emotion regulation
      therapy). 

PMID- 25050180
TI  - Topical anesthesia for cataract surgery: the patients' perspective.
AB  - Purpose. To evaluate the analgesic efficacy of 0.5% propacaine hydrochloride as
      topical anesthesia during phacoemulsification surgery. Methods. Intraoperative
      pain intensity was assessed using a 5-category verbal rating scale during each of
      three surgical stages. Pain scores from each surgical stage and total pain scores
      were compared for the factors of patient age, gender, cataract laterality, and
      type. Results. In comparison of cataract type subgroups, the mean total pain
      scores and mean stage 2 pain scores in both white mature cataract (WMC) and
      corticonuclear plus posterior subcapsular cataract (CN + PSC) groups were
      significantly higher than in the PSC-only (PSC) group (P < 0.05). Conclusion.
      Phacoemulsification with topical anesthesia is not a completely painless
      procedure. Pain intensity varies with cataract type and stage of surgery. 

PMID- 25050178
TI  - Hostility modifies the association between TV viewing and cardiometabolic risk.
AB  - BACKGROUND: It was hypothesized that television viewing is predictive of
      cardiometabolic risk. Moreover, people with hostile personality type may be more
      susceptible to TV-induced negative emotions and harmful health habits which
      increase occurrence of cardiometabolic risk. PURPOSE: The prospective association
      of TV viewing on cardiometabolic risk was examined along with whether hostile
      personality trait was a modifier. METHODS: A total of 3,269 Black and White
      participants in the coronary artery risk development in young adults (CARDIA)
      study were assessed from age 23 to age 35. A cross-lagged panel model at exam
      years 5, 10, 15, and 20, covering 15 years, was used to test whether hours of
      daily TV viewing predicted cardiometabolic risk, controlling confounding
      variables. Multiple group analysis of additional cross-lagged panel models
      stratified by high and low levels of hostility was used to evaluate whether the
      association was modified by the hostile personality trait. RESULTS: The cross
      lagged association of TV viewing at years 5 and 15 on clustered cardiometabolic
      risk score at years 10 and 20 was significant (B = 0.058 and 0.051), but not at
      10 to 15 years. This association was significant for those with high hostility (B
      = 0.068 for exam years 5 to 10 and 0.057 for exam years 15 to 20) but not low
      hostility. CONCLUSION: These findings indicate that TV viewing is positively
      associated with cardiometabolic risk. Further, they indicate that hostility might
      be a modifier for the association between TV viewing and cardiometabolic risk.

PMID- 25050179
TI  - Nurses' Experiences of Nonpatient Factors That Affect Nursing Workload: A Study
      of the PAONCIL Instrument's Nonpatient Factors.
AB  - In the RAFAELA patient classification system, the professional assessment of
      optimal nursing care intensity level (PAONCIL) instrument is used to assess the
      optimal nursing intensity level per unit. The PAONCIL instrument contains an
      overall assessment of the actual nursing intensity level and an additional list
      of central nonpatient factors that may increase or decrease the total nursing
      workload (NWL). The aim of this cross-sectional study was to assess and determine
      which nonpatient factors affect nurses' experiences of their total NWL in both
      outpatient settings and hospitals, as captured through the PAONCIL instrument.
      The data material consisted of PAONCIL questionnaires from 38 units and 37
      outpatient clinics at 11 strategically selected hospitals in Finland, and
      included nurses' answers (n = 1307) to the question of which factors, other than
      nursing intensity, affect total NWL. The methods for data analyses were
      qualitative content analyses. The nonpatient factors that affected nurses'
      experiences of total NWL are "organization of work," "working conditions," "self
      control," and "cooperation." The actual list of nonpatient factors in the PAONCIL
      instrument is to a reasonable extent relevant, but the list should be improved to
      include nurses' actual working conditions and self-control. 

PMID- 25050182
TI  - Treatment of ectopic mandibular second permanent molar with elastic separators.
AB  - Ectopic eruption is a developmental disturbance in which the tooth fails to
      follow its normal eruption pathway. Ectopic eruption of the second molar is
      relatively rare. This paper presents the case of thirteen-year-old male with an
      ectopic mandibular second permanent molar. The condition was corrected with
      surgical exposure and placement of elastic separators. This case report lays
      emphasis on the practice of basic methods to obtain acceptable results rather
      than extensive surgical or orthodontic corrections. It is advised that ectopic
      teeth should not be neglected especially when it concerns developing caries and
      malocclusion. 

PMID- 25050181
TI  - Diffusion imaging of auditory and auditory-limbic connectivity in tinnitus:
      preliminary evidence and methodological challenges.
AB  - Subjective tinnitus, or "ringing in the ears," is perceived by 10 to 15 percent
      of the adult population and causes significant suffering in a subset of patients.
      While it was originally thought of as a purely auditory phenomenon, there is
      increasing evidence that the limbic system influences whether and how tinnitus is
      perceived, far beyond merely determining the patient's emotional reaction to the
      phantom sound. Based on functional imaging and electrophysiological data, recent
      articles frame tinnitus as a "network problem" arising from abnormalities in
      auditory-limbic interactions. Diffusion-weighted magnetic resonance imaging is a
      noninvasive method for investigating anatomical connections in vivo. It thus has
      the potential to provide anatomical evidence for the proposed changes in auditory
      limbic connectivity. However, the few diffusion imaging studies of tinnitus
      performed to date have inconsistent results. In the present paper, we briefly
      summarize the results of previous studies, aiming to reconcile their results.
      After detailing analysis methods, we then report findings from a new dataset. We
      conclude that while there is some evidence for tinnitus-related increases in
      auditory and auditory-limbic connectivity that counteract hearing-loss related
      decreases in auditory connectivity, these results should be considered
      preliminary until several technical challenges have been overcome. 

PMID- 25050183
TI  - Submasseteric tuberculous lesion of mandible: report of a case and review of the
      literature.
AB  - Tuberculosis is still a major health hazard in the developing world, while its
      incidence has recently started to escalate after decreasing for many years. It is
      a chronic granulomatous disease that can affect any part of the body, including
      the oral cavity. Oral lesions of tuberculosis, though uncommon, are seen in both
      the primary and secondary stages of the disease. This paper presents a case of
      tuberculosis of the submasseteric space, manifesting as a persistent swelling at
      ramus and angle of mandible. The diagnosis was confirmed based on histopathology
      after an open incisional biopsy. Patient underwent antituberculosis therapy and
      his extraoral swelling completely resolved after 4 months of the therapy. The
      purpose of this paper is to emphasize the importance of early and definitive
      diagnosis of orofacial tuberculosis, to recognize it based on signs and symptoms,
      and to refer the patients suspected of active tuberculous infection for
      appropriate medical treatment. 

PMID- 25050185
TI  - Use of ultrasound to diagnose and manage a five-liter empyema in a rural clinic
      in sierra leone.
AB  - We report the case of a dyspneic patient with a five-liter pleural empyema that
      was diagnosed and managed in a resource-limited clinic in a rural part of Sierra
      Leone. The diagnosis and management of this condition are usually guided by
      imaging modalities such as X-rays or CT scans. However, these resources may not
      be available in austere settings in developing countries. Because emergency
      physicians work in a variety of clinical settings, they should be well versed in
      the use of portable ultrasound machines to diagnose, treat, and manage many
      different conditions. 

PMID- 25050184
TI  - Van der woude syndrome with short review of the literature.
AB  - Van der Woude syndrome (VWS) is a rare autosomal dominant condition with high
      penetrance and variable expression. Clinical manifestation of this autosomal
      dominant clefting syndrome includes bilateral midline lower lip pits, cleft lip,
      and cleft palate along with hypodontia. These congenital lip pits appear as a
      malformation in the vermilion border of the lip, with or without excretion.
      Discomfort caused by spontaneous or induced drainage of saliva/mucus when
      pressure is applied or during a meal as well as poor aesthetic match is one of
      the main complaints of patients with congenital lip fistula. The pits are treated
      by surgical resection. Dentists should be aware of the congenital lip pits as in
      Van der Woude syndrome because they have been reported to be associated with a
      variety of malformations or other congenital disorders. Here, the authors report
      a rare case of Van der Woude syndrome with short review of the literature. 

PMID- 25050186
TI  - Concomitant alpha- and gamma-sarcoglycan deficiencies in a Turkish boy with a
      novel deletion in the alpha-sarcoglycan gene.
AB  - Limb-girdle muscular dystrophy type 2D (LGMD-2D) is caused by autosomal recessive
      defects in the alpha-sarcoglycan gene located on chromosome 17q21. In this study,
      we present a child with alpha-sarcoglycanopathy and describe a novel deletion in
      the alpha-sarcoglycan gene. A 5-year-old boy had a very high serum creatinine
      phosphokinase level, which was determined incidentally, and a negative molecular
      test for the dystrophin gene. Muscle biopsy showed dystrophic features.
      Immunohistochemistry showed that there was diminished expression of alpha- and
      gamma-sarcoglycans. DNA analysis revealed a novel 7 bp homozygous deletion in
      exon 3 of the alpha-sarcoglycan gene. His parents were consanguineous
      heterozygous carriers of the same deletion. We believe this is the first
      confirmed case of primary alpha-sarcoglycanopathy with a novel deletion in
      Turkey. In addition, this study demonstrated that both muscle biopsy and DNA
      analysis remain important methods for the differential diagnosis of muscular
      dystrophies because dystrophinopathies and sarcoglycanopathies are so similar. 

PMID- 25050187
TI  - Anti-GBM of Pregnancy: Acute Renal Failure Resolved after Spontaneous Abortion,
      Plasma Exchange, Hemodialysis, and Steroids.
AB  - Antiglomerular basement membrane disease presenting during pregnancy is very
      uncommon. We present a case of a pregnant female who presented with acute renal
      failure needing dialysis from Goodpasture's disease. She responded very well to
      just plasma exchange, high dose steroids, and hemodialysis. Cyclophosphamide was
      never started on this patient. She had a spontaneous abortion in her 8th week of
      pregnancy and henceforth did very well to regain her renal function. Patient
      became hemodialysis independent at 2 months and returned to her baseline kidney
      function at 6 months. We present this remarkable case of recovery from acute
      renal failure in a patient with anti-GBM disease. We think the flare-up of renal
      failure was pregnancy related which resolved after spontaneous abortion. 

PMID- 25050188
TI  - Massive femoral osteolysis secondary to loosening of a cemented roughened long
      stem: a case report.
AB  - The surface finish of a femoral stem plays an important role in the longevity of
      cemented total hip arthroplasty. In efforts to decrease the rate of aseptic
      loosening, some prostheses have been designed to have a roughened surface that
      enhances bonding between the prosthesis and cement, but clinical outcomes remain
      controversial. We present a rare case of massive osteolysis with extreme femoral
      expansion that developed after cemented revision total hip arthroplasty. The
      destructive changes in the femur were attributable to abnormal motion of the stem
      and were aggravated by the roughened precoated surface of the long femoral
      component. Revision surgery using a total femur prosthesis was performed because
      there was insufficient remaining bone to fix the new prosthesis. The surgical
      technique involved wrapping polypropylene meshes around the prosthesis to create
      an insertion for the soft tissue, which proved useful for preventing muscular
      weakness and subsequent dislocation of the hip. 

PMID- 25050189
TI  - Differential profile of ultrasound findings associated with malignancy in mixed
      and solid thyroid nodules in an elderly female population.
AB  - Objective. Ultrasonographic characteristics are associated with thyroid
      malignancy. Our aim was to compare the diagnostic value of ultrasound features in
      the detection of thyroid malignancy in both solid and mixed nodules. Methods. We
      prospectively studied female patients (>=50 years) referred to ultrasound-guided
      fine needle aspiration biopsy. Ultrasound features considered suspicious were
      hypoechogenicity, microcalcifications, irregular margins, high anteroposterior
      (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed
      and solid nodules. Results. In a group of 504 elderly female patients (age = 69
      +/- 8 years), the frequency of malignant cytology was 6%. Thirty-one percent of
      nodules were mixed and 60% were solid. The rate of malignant cytology was similar
      for mixed and solid nodules (7.4 versus 5.8%, P: 0.56). While in mixed nodules
      none of the ultrasound characteristics were associated with malignant cytology,
      in solid nodules irregular margins and microcalcifications were significant (all
      P < 0.05). The combination of irregular margins and/or microcalcifications
      significantly increased the association with malignant cytology only in solid
      nodules (OR: 2.76 (95% CI: 1.25-6.10), P: 0.012). Conclusions. Ultrasound
      features were of poor diagnostic value in mixed nodules, which harbored malignant
      lesions as often as solid nodules. Our findings challenge the recommended minimal
      size for ultrasound-guided fine needle aspiration biopsy in mixed nodules. 

PMID- 25050190
TI  - Quantification of photocyanine in human serum by high-performance liquid
      chromatography-tandem mass spectrometry and its application in a pharmacokinetic
      study.
AB  - Photocyanine is a novel anticancer drug. Its pharmacokinetic study in cancer
      patients is therefore very important for choosing doses, and dosing intervals in
      clinical application. A rapid, selective and sensitive high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and
      validated for the determination of photocyanine in patient serum. Sample
      preparation involved one-step protein precipitation by adding methanol and N,N
      dimethyl formamide to 0.1 mL serum. The detection was performed on a triple
      quadrupole tandem mass spectrometer operating in multiple reaction-monitoring
      (MRM) mode. Each sample was chromatographed within 7 min. Linear calibration
      curves were obtained for photocyanine at a concentration range of 20-2000 ng/mL
      (r > 0.995), with the lower limit of quantification (LLOQ) being 20 ng/mL. The
      intrabatch accuracy ranged from 101.98% to 107.54%, and the interbatch accuracy
      varied from 100.52% to 105.62%. Stability tests showed that photocyanine was
      stable throughout the analytical procedure. This study is the first to utilize
      the HPLC-MS/MS method for the pharmacokinetic study of photocyanine in six cancer
      patients who had received a single dose of photocyanine (0.1 mg/kg) administered
      intravenously. 

PMID- 25050191
TI  - Rapid Burkholderia pseudomallei identification and antibiotic resistance
      determination by bacteriophage amplification and MALDI-TOF MS.
AB  - Phage amplification detected by MALDI-TOF MS was investigated for rapid and
      simultaneous Burkholderia pseudomallei identification and ceftazidime resistance
      determination. B. pseudomallei ceftazidime susceptible and resistant DeltapurM
      mutant strains Bp82 and Bp82.3 were infected with broadly targeting B.
      pseudomallei phage phiX216 and production of the m/z 37.6 kDa phage capsid
      protein observed by MALDI-TOF MS over the course of 3 h infections. This allowed
      for repoducible phage-based bacterial ID within 2 h of the onset of infection.
      MALDI-TOF MS-measured time to detection correlated with in silico modeling, which
      predicted an approximate 2 h detection time. Ceftazidime susceptible strain Bp82,
      while detectable in the absence of the drug, owing to the reliance of phage
      amplification on a viable host, was not detectable when 10 MUg/mL ceftazidime was
      added at the onset of infection. In contrast, resistant strain Bp82.3 was
      detected in the same 2 h timeframe both with and without the addition of
      ceftazidime.

PMID- 25050192
TI  - The heat shock protein-CD91 pathway mediates tumor immunosurveillance.
AB  - Tumor immunosurveillance can be readily observed in mice and humans. Here, we
      examine how T-cell responses are primed during tumorigenesis, a condition in
      which immunostimulatory antigens are extraordinarily scarce. We recently
      demonstrated that the HSP-CD91 pathway is indispensable for antigen cross
      presentation, and thus immunosurveillance, in cancer.

PMID- 25050193
TI  - Immunogenic and tolerogenic effects of the chimeric IL-2-diphtheria toxin
      cytocidal agent Ontak(r) on CD25+ cells.
AB  - Ontak(r), a conjugate between IL-2 and a diphtheria toxin fragment, was recently
      investigated in cancer clinical trials aiming to kill CD25+ regulatory T cells
      (Tregs). We found that the activity of Ontak(r) was more complex on Tregs and
      conventional T cells (Tconvs) than anticipated, including a novel strong
      influence on dendritic cells (DCs).

PMID- 25050194
TI  - Combined OX40 ligation plus CTLA-4 blockade: More than the sum of its parts.
AB  - It is becoming clear that combination strategies will be necessary to augment
      cancer immunotherapy. We report that combination anti-OX40/anti-CTLA-4 mAb
      immunotherapy improves survival by enhancing effector T cell expansion and
      function, even while inducing Th2 cytokine production. Furthermore, IL-4 blockade
      in addition to combination therapy significantly improved anti-tumor efficacy.

PMID- 25050195
TI  - Synergistic antitumor effects of a TGFbeta inhibitor and cyclophosphamide.
AB  - In a mouse model of breast carcinoma, the combination of cyclophosphamide and
      transforming growth factor beta1,2,3 (TGFbeta1,2,3)-targeting antibody achieved
      superior antineoplastic effects. This novel paradigm of synergistic
      chemoimmunotherapy promises to improve the clinical outcome of cancer patients
      with micrometastases, and thus deserves further investigation.

PMID- 25050196
TI  - Dual targeting of CD137 co-stimulatory and PD-1 co-inhibitory molecules for
      ovarian cancer immunotherapy.
AB  - We recently demonstrated that simultaneous targeting of CD137 co-stimulatory and
      programmed cell death 1 (PD-1) co-inhibitory molecules synergistically induced an
      anticancer immune response in the ID8 syngeneic orthotopic mouse ovarian
      carcinoma model. We further showed that the therapeutic efficacy was enhanced by
      treatment with cisplatin. These findings provide a rationale for evaluating dual
      targeting of CD137/PD-1 co-signaling molecules in ovarian cancer patients.

PMID- 25050197
TI  - Activity of cytokine-induced killer cells against bone and soft tissue sarcoma.
AB  - Cytokine-induced killer (CIK) cells are T lymphocytes expanded ex vivo that are
      endowed with MHC-independent tumoricidal activity. We have recently demonstrated,
      in a preclinical setting, that CIK cells are active against autologous bone and
      soft tissue sarcomas. In particular, CIK cells killed a putative sarcoma stem
      cell population that may underlie disease relapse and chemoresistance.

PMID- 25050198
TI  - The role of CUX1 in antagonizing NF-kappaB signaling in TAMs.
AB  - Macrophages represent a major component of the tumor microenvironment and
      contribute to neoplasia initiation and cancer progression. However, the molecular
      mechanisms underlying these phenomena are only partially understood. Manipulating
      the transcriptional activity of the macrophage functional specification factor NF
      kappaB by virtue of a novel regulatory factor cut-like homeobox 1 (CUX1) may
      provide a potential target for therapeutic intervention.

PMID- 25050199
TI  - The microbiome modulates the tumor macroenvironment.
AB  - Earlier investigations of the tumor microenvironment unveiled systemic networks
      presenting novel therapeutic opportunities. It has been recently shown that gut
      microbes modulate whole host immune and neuroendocrine factors impacting the fate
      of distant preneoplastic lesions toward malignancy or regression. These findings
      establish a new paradigm of holobiont therapeutic engineering in emerging tumor
      macroenvironments.

PMID- 25050200
TI  - Tumor vascularity in ovarian cancer: T cells need breathing room.
AB  - Tumor-infiltrating lymphocytes (TILs) are crucial for effective antitumor
      responses. However, hypoxia can skew T-cell differentiation and function, thereby
      perturbing TILs. We have demonstrated that TILs and their immune function are
      associated with tumor vascularization. These features are prognostic for improved
      disease-specific survival in ovarian cancer. Thus, new immunotherapies should
      consider how hypoxia impacts antitumor immunity.

PMID- 25050201
TI  - Lymphocyte-derived interleukin-17A adds another brick in the wall of inflammation
      induced breast carcinogenesis.
AB  - We have previously reported that a subset of breast tumors are infiltrated with
      IL-17A-producing tumor-associated lymphocytes and that IL-17A cytokine is
      principally associated with estrogen receptor negative (ER-) and triple negative,
      basal-like tumors. We established that IL-17A producing lymphocytes induced
      cancer cell proliferation, chemoresistance, and invasion, indicating that IL-17A
      is a potential therapeutic target for breast malignancies.

PMID- 25050203
TI  - Sleep apnea awakens cancer: A unifying immunological hypothesis.
AB  - The presence of obstructive sleep apnea (OSA) in patients with cancer appears to
      be accompanied by poorer outcomes. However, the mechanisms underlying such
      association are unknown. We hypothesize that the constitutive characteristics of
      OSA, namely, intermittent hypoxia and sleep fragmentation, promote changes in the
      tumor microenvironment that ultimately lead to a disadvantageous
      immunosurveillance, thereby accelerating tumor proliferation and enhancing its
      invasiveness.

PMID- 25050202
TI  - Synthetic induction of immunogenic cell death by genetic stimulation of
      endoplasmic reticulum stress.
AB  - Cis-diamminedichloridoplatinum(II) (CDDP), commonly referred to as cisplatin, is
      a chemotherapeutic drug used for the treatment of a wide range of solid cancers.
      CDDP is a relatively poor inducer of immunogenic cell death (ICD), a cell death
      modality that converts dying cells into a tumor vaccine, stimulating an immune
      response against residual cancer cells that permits long-lasting immunity and a
      corresponding reduction in tumor growth. The incapacity of CDDP to trigger ICD is
      at least partially due to its failure to stimulate the premortem endoplasmic
      reticulum (ER)-stress response required for the externalization of the "eat-me"
      signal calreticulin (CRT) on the surface of dying cancer cells. Here, we
      developed a murine cancer cell line genetically modified to express the ER
      resident protein reticulon-1c (Rtn-1c) by virtue of tetracycline induction and
      showed that enforced Rtn-1c expression combined with CDDP treatment promoted CRT
      externalization to the surface of cancer cells. In contrast to single agent
      treatments, the tetracycline-mediated Rtn-1c induction combined with CDDP
      chemotherapy stimulated ICD as measured by the capacity of dying tumor cells,
      inoculated into syngenic immunocompetent mice, to mount an immune response to
      tumor re-challenge 1 week later. More importantly, established tumors, forced to
      constitutively express Rtn-1c in vivo by continuous treatment with tetracycline,
      became responsive to CDDP and exhibited a corresponding reduction in the rate of
      tumor growth. The combined therapeutic effects of Rtn-1c induction with CDDP
      treatment was only detected in the context of an intact immune system and not in
      nu/nu mice lacking thymus-dependent T lymphocytes. Altogether, these results
      indicate that the artificial or "synthetic" induction of immunogenic cell death
      by genetic manipulation of the ER-stress response can improve the efficacy of
      chemotherapy with CDDP by stimulating anticancer immunity.

PMID- 25050204
TI  - Engineered chimeric antigen receptor-expressing T cells for the treatment of
      pancreatic ductal adenocarcinoma.
AB  - Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells is
      under investigation as an approach to restore productive T cell
      immunosurveillance in patients with pancreatic ductal adenocarcinoma. Early
      findings demonstrate safety of this cell-based therapy and the capacity of CAR
      expressing T cells to mediate anti-tumor activity as well as induce endogeneous
      antitumoral immune responses.

PMID- 25050205
TI  - KLRG1+ natural killer cells protect against pulmonary metastatic disease by
      immunosurveillance.
AB  - Natural killer cells (NK cells) play a key role in cancer immunosurveillance.
      However, their activity is highly dependent upon their maturation stage, which in
      turn relates to organ distribution. Here, we discuss the role of intrinsic master
      transcription factors and extrinsic IL-15 signaling on NK cell-mediated immune
      protection against murine pulmonary metastasis.

PMID- 25050206
TI  - Natural killer T cell strategies to combat Epstein-Barr virus infection.
AB  - Epstein-Barr virus (EBV) infection results in rapid loss of CD1d expression from
      the surface of infected B cells, thus enabling the virus to evade immune
      recognition by natural killer T (NKT) cells. Using pharmacologic means to boost
      CD1d expression, potent NKT cell effector functions can be elicited toward EBV
      infected B cells, suggesting the promise of novel strategies to target EBV
      associated diseases such as some B-cell malignancies.

PMID- 25050209
TI  - The ELR+CXCL chemokines and their receptors CXCR1/CXCR2: A signaling axis and new
      target for the treatment of renal cell carcinoma.
AB  - The long-term efficacy of anti-angiogenesis drugs targeting vascular endothelial
      growth factor (VEGF) and VEGF receptors in the treatment of renal cell carcinoma
      (RCC) has been lacking. We have shown that the ELR+CXCL cytokines and their (C-X
      C) chemokine receptors, namely CXCR1 and CXCR2, stimulate cancer cell
      proliferation, tumor inflammation, and angiogenesis. Hence, this essential
      molecular nexus regulating cancer growth represents a key therapeutic target.

PMID- 25050208
TI  - Myeloid-derived cells are key targets of tumor immunotherapy.
AB  - Tumors are composed of heterogeneous cell populations recruited by cancer cells
      to promote growth and metastasis. Among cells comprising the tumor stroma,
      myeloid-derived cells play pleiotropic roles in supporting tumorigenesis at
      distinct stages of tumor development. The tumor-infiltrating myeloid cell
      contingent is composed of mast cells, neutrophils, dendritic cells, macrophages,
      and myeloid-derived suppressor cells. Such cells are capable of evading the
      hostile tumor environment typically prone to immune cell destruction and can even
      promote angiogenesis, chronic inflammation, and invasion. This paper briefly
      summarizes the different myeloid-derived subsets that promote tumor development
      and the strategies that have been used to counteract the protumorigenic activity
      of these cells. These strategies include myeloid cell depletion, reduction of
      recruitment, and inactivation or remodeling of cell phenotype. Combining drugs
      designed to target tumor myeloid cells with immunotherapies that effectively
      trigger antitumor adaptive immune responses holds great promise in the
      development of novel cancer treatments.

PMID- 25050207
TI  - Trial Watch: Adoptive cell transfer for anticancer immunotherapy.
AB  - The expression "adoptive cell transfer" (ACT) is commonly employed to indicate an
      immunotherapeutic regimen involving the isolation of autologous blood-borne or
      tumor-infiltrating lymphocytes, their selection/expansion/activation ex vivo, and
      their reinfusion into the patient, most often in the context of lymphodepleting
      pre-conditioning and in combination with immunostimulatory treatments.
      Optionally, the cellular material for ACT is genetically manipulated before
      expansion to (1) target specific tumor-associated antigens; (2) endogenously
      express immunostimulatory molecules; and/or (3) persist for long periods upon
      reinfusion. Consistent efforts have been dedicated at the amelioration of this
      immunotherapeutic regimen throughout the past decade, resulting in the
      establishment of ever more efficient and safer ACT protocols. Accordingly, the
      number of clinical trials testing ACT in oncological indications does not cease
      to increase. In this Trial Watch, we summarize recent developments in this
      exciting area of research, covering both high-impact studies that have been
      published during the last 12 months and clinical trials that have been launched
      in the same period to evaluate the safety and therapeutic potential of ACT in
      cancer patients.

PMID- 25050210
TI  - A novel combinatorial cancer immunotherapy: poly-IC and blockade of the PD-1/PD
      L1 pathway.
AB  - A non-antigen specific immunotherapy consisting of repeated co-administration of
      poly-IC and blocking antibodies targeting the programmed cell death-1 (PD-1)
      pathway dramatically inhibits tumor development in several mouse models of
      cancer. Tumor-reactive CD8+ T cells mediate the antitumor effects mediated by PD
      1 blockade. This therapeutic avenue can be readily translated to cancer patient
      treatment regimens.

PMID- 25050211
TI  - Macrophages in the liver prevent metastasis by efficiently eliminating
      circulating tumor cells after monoclonal antibody immunotherapy.
AB  - Monoclonal antibodies (mAbs) are increasingly being used to treat cancer. In
      response to mAb therapy, we have identified macrophages in the liver as major
      effector cells removing circulating tumor cells via antibody-dependent
      phagocytosis, an immune cell-mediated process that prevented liver metastasis.
      This discovery extends our understanding of the mechanisms of mAb therapy, and
      may help to optimize mAb-based anticancer therapeutics.

PMID- 25050212
TI  - Sarcoma response to targeted therapy dynamically polarizes tumor-associated
      macrophages.
AB  - In gastrointestinal stromal tumor (GIST), the most common human sarcoma, tumor
      associated macrophages (TAMs) have been found to be abundant and surprisingly M1
      like, exhibiting antitumoral activities. However, TAMs switch to M2-like during
      the course of imatinib therapy, but upon drug resistance TAMs revert to M1-like.
      Therefore, the oncologic efficacy of TAM depletion may depend on tumor type and
      treatment status.

PMID- 25050213
TI  - Rethinking the role of myeloid-derived suppressor cells in adoptive T-cell
      therapy for cancer.
AB  - The expansion of cancer-induced myeloid cells is thought to be one of the main
      obstacles to successful immunotherapy. Nevertheless, in murine tumors undergoing
      immune-mediated destruction by adoptively transferred T cells, we have recently
      shown that such cells maintain their immunosuppressive properties. Therefore,
      adoptive T-cell therapy can, under certain conditions, overcome myeloid cell
      immunosuppression.

PMID- 25050214
TI  - Screening of novel immunogenic cell death inducers within the NCI Mechanistic
      Diversity Set.
AB  - Immunogenic cell death (ICD) inducers can be defined as agents that exert
      cytotoxic effects while stimulating an immune response against dead cell
      associated antigens. When initiated by anthracyclines, ICD is accompanied by
      stereotyped molecular changes, including the pre-apoptotic exposure of
      calreticulin (CRT) on the cell surface, the lysosomal secretion of ATP during the
      blebbing phase of apoptosis, and the release of high mobility group box 1 (HMGB1)
      from dead cells. By means of genetically engineered human osteosarcoma U2OS
      cells, we screened the 879 anticancer compounds of the National Cancer Institute
      (NCI) Mechanistic Diversity Set for their ability to promote all these hallmarks
      of ICD in vitro. In line with previous findings from our group, several cardiac
      glycosides exhibit a robust propensity to elicit the major manifestations of ICD
      in cultured neoplastic cells. This screen pointed to septacidin, an antibiotic
      produced by Streptomyces fibriatus, as a novel putative inducer of ICD. In low
      throughput validation experiments, septacidin promoted CRT exposure, ATP
      secretion and HGMB1 release from both U2OS cells and murine fibrosarcoma MCA205
      cells. Moreover, septacidin-killed MCA205 cells protected immunocompetent mice
      against a re-challenge with living cancer cells of the same type. Finally, the
      antineoplastic effects of septacidin on established murine tumors were entirely
      dependent on T lymphocytes. Altogether, these results underscore the suitability
      of the high-throughput screening system described here for the identification of
      novel ICD inducers.

PMID- 25050216
TI  - Immune response markers in sentinel nodes may predict melanoma progression.
AB  - We recently reported that variable expression of immune-response genes
      distinguishes tumor positive sentinel nodes in melanoma patients with malignant
      progression from those with non-progressing disease. Our results depict sentinel
      nodes as sites in which immune functions are associated with metastatic disease
      and identify CD30 as a host immune-related cancer prognostic marker and potential
      therapeutic target.

PMID- 25050215
TI  - Secretory pathways generating immunosuppressive NKG2D ligands: New targets for
      therapeutic intervention.
AB  - Natural Killer Group 2 member D (NKG2D) activating receptor, present on the
      surface of various immune cells, plays an important role in activating the
      anticancer immune response by their interaction with stress-inducible NKG2D
      ligands (NKG2DL) on transformed cells. However, cancer cells have developed
      numerous mechanisms to evade the immune system via the downregulation of NKG2DL
      from the cell surface, including the release of NKG2DL from the cell surface in a
      soluble form. Here, we review the mechanisms involved in the production of
      soluble NKG2DL (sNKG2DL) and the potential therapeutic strategies aiming to block
      the release of these immunosuppressive ligands. Therapeutically enabling the
      NKG2D-NKG2DL interaction would promote immunorecognition of malignant cells, thus
      abrogating disease progression.

PMID- 25050217
TI  - Radiation and anti-PD-L1 antibody combinatorial therapy induces T cell-mediated
      depletion of myeloid-derived suppressor cells and tumor regression.
AB  - Tumor relapse after radiotherapy may be due to the upregulation of programmed
      cell death ligand 1 (PD-L1). We demonstrated that anti-PD-L1 antibody synergizes
      with radiation to control local and distal tumors. CD8+T cells mediated antitumor
      effects of the combination therapy by the reduction of myeloid-derived suppressor
      cells (MDSCs) via tumor-necrosis factor (TNF)-mediated signaling. Our study
      provides insight into immune- and radiation-based combinational therapies.

PMID- 25050218
TI  - Discovering cancer immunotherapy targets in vivo.
AB  - A key challenge facing the cancer immunology field is the discovery of the most
      suitable targets for therapeutic intervention. We recently reported a novel RNA
      interference (RNAi)-based approach for systematic discovery of such targets in
      the tumor microenvironment in vivo utilizing pooled shRNA libraries as a
      screening tool. Here, we discuss applying this unbiased method to develop
      innovative cancer therapeutics.

PMID- 25050219
TI  - Iron-induced parafibrin formation in tumors fosters immune evasion.
AB  - Although efficacious in vitro, it is well known that adoptive immunotherapeutic
      modalities lose their potency when applied in vivo. Furthermore, malignant cell
      exposure to blood platelets attenuates the anticancer activity of natural killer
      (NK) cells. We argue that upon contact with redox iron, fibrinogen is converted
      to a hydrophobic fibrin-like polymer that coats tumor cells and provides
      protection from immune-mediated destruction.

PMID- 25050220
TI  - Dual therapeutic benefit of electroporation-mediated DNA vaccination in vivo:
      Enhanced gene transfer and adjuvant activity.
AB  - DNA vaccination consists of administering an antigen-coding nucleotide sequence.
      In order to improve the efficacy of DNA vaccines, electroporation is one of the
      most commonly used methods to enhance DNA uptake. Here, we discuss additional
      immunological effects of electroporation that are key aspects for inducing
      immunity in response to DNA vaccines.

PMID- 25050221
TI  - Smac mimetics combined with innate immune stimuli create the perfect cytokine
      storm to kill tumor cells.
AB  - A dual immunotherapy approach employing small-molecule inhibitors of apoptosis
      (IAP) protein antagonists in combination with innate immune stimuli has proven to
      be highly synergistic and effective in animal tumor models. This strategy
      overcomes many of the limitations of either single agent therapy and our results
      suggest that the combination could be easily and effectively translated to the
      clinic.

PMID- 25050222
TI  - A critical role for natural killer cells in dendritic cell-based anticancer
      immunotherapy.
AB  - Multipronged immunotherapies that activate both T cells and natural killer (NK)
      cells may result in more robust and durable anticancer responses. The successful
      outcome of dendritic cell (DC)-based vaccination therapy involves a hitherto
      unrecognized role for NK cells. Combinatorial regimens that enhance the
      contribution of NK cells to the anticancer immune response may therefore improve
      clinical outcomes.

PMID- 25050223
TI  - T cell immunosurveillance controls B lymphoma development.
AB  - We recently showed a critical role for T cells in the immunosurveillance of
      nascent B cell lymphomas arising from mutations impacting plasma cell
      differentiation. Our data suggest that CD8+ T cells continuously eliminate
      mutated B cells that fail to downregulate their co-stimulatory machinery and the
      Fas death receptor, thus constraining B lymphoma pathogenesis.

PMID- 25050224
TI  - IFNalpha induces prolonged remissions modeling curative immunologic responses in
      chronic myeloid leukemia.
AB  - Tyrosine kinase inhibitor therapy has dramatically changed the outcome of chronic
      myeloid leukemia (CML) patients. However, the treatment is not considered to be
      curative and may present deleterious side effects, such that additional therapy
      options are warranted. Here, we discuss the beneficial immunomodulatory effects
      of interferon alpha (IFNalpha) therapy and the immunological changes related to
      optimal treatment responses.

PMID- 25050225
TI  - Transplantation-induced cancers: Emerging evidence that clonal CMV-specific NK
      cells are causal immunogenic factors.
AB  - Solid cancers are a major adverse outcome of liver transplantation. Recent
      reassessments have revealed insights into causal factors, primarily centering on
      modulations of the natural killer (NK) cell compartment in liver transplant
      recipients. In the presence of cytomegalovirus, the clonal expansion of
      differentiated NK cells could restrict the diversity of the NK repertoire
      favoring the development of certain tumors.

PMID- 25050226
TI  - Corroles: synthesis, functionalization and application as chemosensors.

PMID- 25050227
TI  - Highly Efficient and Stereoselective Construction of Bispirooxindole Derivatives
      via a Three-Component 1,3-Dipolar Cycloaddition Reaction.
AB  - A highly regio- and stereoselective synthesis of bispirooxindoles by 1,3-dipolar
      cycloaddition of in situ generated azomethine ylides from isatin and proline to
      different electron-deficient alkenes has been developed. The synthesis affords
      the desired bispiro scaffold compounds in excellent yields with high
      regioselectivity under mild conditions. The stereochemistry was determined by
      single-crystal X-ray analysis. 

PMID- 25050228
TI  - Synthesis and photochromic properties of configurationally varied azobenzene
      glycosides.
AB  - Spatial orientation of carbohydrates is a meaningful parameter in carbohydrate
      recognition processes. To vary orientation of sugars with temporal and spatial
      resolution, photosensitive glycoconjugates with favorable photochromic properties
      appear to be opportune. Here, a series of azobenzene glycosides were synthesized,
      employing glycoside synthesis and Mills reaction, to allow "switching" of
      carbohydrate orientation by reversible E/Z isomerization of the azobenzene N=N
      double bond. Their photochromic properties were tested and effects of azobenzene
      substitution as well as the effect of anomeric configuration and the orientation
      of the sugars 2-hydroxy group were evaluated. 

PMID- 25050229
TI  - An improved rapid mixing device for time-resolved electrospray mass spectrometry
      measurements.
AB  - Time series data can provide valuable insight into the complexity of biological
      reactions. Such information can be obtained by mass-spectrometry-based approaches
      that measure pre-steady-state kinetics. These methods are based on a mixing
      device that rapidly mixes the reactants prior to the on-line mass measurement of
      the transient intermediate steps. Here, we describe an improved continuous-flow
      mixing apparatus for real-time electrospray mass spectrometry measurements. Our
      setup was designed to minimize metal-solution interfaces and provide a sheath
      flow of nitrogen gas for generating stable and continuous spray that consequently
      enhances the signal-to-noise ratio. Moreover, the device was planned to enable
      easy mounting onto a mass spectrometer replacing the commercial electrospray
      ionization source. We demonstrate the performance of our apparatus by monitoring
      the unfolding reaction of cytochrome C, yielding improved signal-to-noise ratio
      and reduced experimental repeat errors. 

PMID- 25050230
TI  - Magnetic resonance access to transiently formed protein complexes.
AB  - Protein-protein interactions are of utmost importance to an understanding of
      biological phenomena since non-covalent and therefore reversible couplings
      between basic proteins leads to the formation of complex regulatory and adaptive
      molecular systems. Such systems are capable of maintaining their integrity and
      respond to external stimuli, processes intimately related to living organisms.
      These interactions, however, span a wide range of dissociation constants, from
      sub-nanomolar affinities in tight complexes to high-micromolar or even millimolar
      affinities in weak, transiently formed protein complexes. Herein, we demonstrate
      how novel NMR and EPR techniques can be used for the characterization of weak
      protein-protein (ligand) complexes. Applications to intrinsically disordered
      proteins and transiently formed protein complexes illustrate the potential of
      these novel techniques to study hitherto unobserved (and unobservable) higher
      order structures of proteins. 

PMID- 25050231
TI  - Antimalarial natural products: a review.
AB  - OBJECTIVE: Malaria is an infectious disease commonplace in tropical countries.
      For many years, major antimalarial drugs consisted of natural products, but since
      1930s these drugs have been largely replaced with a series of synthetic drugs.
      This article tries to briefly indicate that some plants which previously were
      used to treat malaria, as a result of deficiencies of synthetic drugs, have
      revived into useful products once more. It also attempts to describe some tests
      which can be used to evaluate plant extracts for antimalarial activity. MATERIALS
      AND METHODS: By referring to some recent literatures, data were collected about
      plants used for the treatment of malaria, evaluation of plant extracts for
      antimalarial activity, modes of action of natural antimalarial agents, and recent
      research on antimalarial plants in Iran and other countries. RESULTS AND
      CONCLUSION: There is an urgent need for the development of new treatments for
      malaria. Many countries have a vast precedence in the use of medicinal plants and
      the required knowledge spans many centuries. Although malaria is controlled in
      Iran, some researchers tend to study malaria and related subjects. In vitro
      biological tests for the detection of antimalarial activities in plant extracts
      are currently available. It is vital that the efficacy and safety of traditional
      medicines be validated and their active constituents be identified in order to
      establish reliable quality control measures.

PMID- 25050232
TI  - Preventive effects of Prangos ferulacea (L.) Lindle on liver damage of diabetic
      rats induced by alloxan.
AB  - OBJECTIVES: Diabetes mellitus is associated with biochemical, physiological and
      pathological alterations in the liver. The aim of this study was to investigate
      the effects of hydroalcoholic extract of Prangos ferulacea (L.) Lindle (P.f) on
      changes in rats' liver structure and serum activities of alanin and aspartate
      aminotransferases after alloxan injection. MATERIALS AND METHODS: In this study,
      forty female Wistar rats with body weight of 200+/-20 g were randomly divided
      into 5 groups with 8 rats per group. Diabetes was induced in rats by alloxan
      monohydrate at dose of 120 mg/kg body weight (BW) injected intraperitoneally.
      Root and leaves with stems hydroalcoholic extract of P.f at dose of 100 mg/kg BW
      were given orally in diabetic rats daily for a month. RESULTS: In diabetic rats
      (D) the serum allanin aminotransferases (ALT) and aspartate aminotransferases
      (AST) were significantly increased (p<0.05) in comparison with the other groups.
      Moreover, in this group, necrosis of hepatocytes, cytoplasmic vacuolations, and
      lymphocytic inflammation were observed. Diabetic rats treated by root extract of
      P.f compared with diabetic group showed a significant decrease in these enzymes.
      In addition, in this group all of previous signs were improved. CONCLUSION: Root
      hydroalcoholic extract of P.f found to influence changes of aminotransferases and
      prevent the histopathological changes of liver associated with alloxan diabetes
      in rats.

PMID- 25050233
TI  - Evaluation of the anti-depressant activity of Myristica fragrans (Nutmeg) in male
      rats.
AB  - OBJECTIVE: The present study was undertaken to evaluate anti-depressant activity
      of Myristica fragrans (MS). MATERIALS AND METHODS: Male Wistar rats were
      subjected to imipramine and herbal extract of MS for their antidepressant
      activity using Forced Swimming Test (FST), Reserpine Reversal Test (RRT),
      Haloperidol-Induced Catalepsy (HIC), and Pentobarbitone Sleeping Time (PST).
      RESULTS: Administration of MS and imipramine revealed a statistically significant
      reduction in immobility time in FST, RRT, and protection against HIC, compared to
      the control group. However, there was no significant potentiation of PST.
      CONCLUSION: Our study demonstrated the potential antidepressant activity of MS.

PMID- 25050234
TI  - Evaluation of antioxidant activity of three common potato (Solanum tuberosum)
      cultivars in Iran.
AB  - OBJECTIVES: Potato (Solanum tuberosum L.), as a whole food, contains high levels
      of vitamins and important antioxidants including phenolic acids, carotenoids and
      flavonoids. The objective of this study was to determine the total phenolic
      content and antioxidant activities of three common potatoes (Solanum tuberosum)
      cultivars in Iran i.e., Savalan, Agria and Sante. MATERIALS AND METHODS: Phenolic
      compound extraction of samples was done with methanol and total phenolic on the
      basis of folin-ciocalteu assay was estimated as 16.58 to 36.24 mg GAE/100g dry
      sample. The antioxidant activities of potato extracts on the basis of inhibition
      of linoleic acid peroxidation and DPPH assay were compared with a commercially
      available antioxidant, alpha -tocopherol. RESULTS: Savalan had the highest
      phenolic content and the highest DPPH radical scavenging activity with EC50 value
      of 41.815+/-mg/ml (DB). Also Savalan had the best inhibitory action against
      linoleic acid oxidation at 94.10+/-1.89% at 50 mg/ml sample concentration.
      Methanolic potato extracts had better antioxidant activity than alpha-tocopherol.
      Significant (p<0.01) negative correlation was observed between total phenolic
      content and the EC50 for DPPH radical scavenging activity(R=-0.877), but there
      was no correlation between total phenolic content and total antioxidant activity.
      CONCLUSION: Metanolic extracts of three potato cultivars are able to inhibit the
      oxidation process. The correlation between total phenolic content and DPPH
      radical scavenging activity indicates that phenolic compounds are responsible for
      antiradical activity.

PMID- 25050235
TI  - Acute Datura Stramonium poisoning in East of Iran - a case series.
AB  - OBJECTIVES: Datura Stramonium (DS) is a common weed along roadsides, in
      cornfields and pastures and in waste areas. It belongs to the family Solanaceae
      and its toxic components are tropane belladonna alkaloids. It has been used
      voluntarily by teenagers for its hallucinogenic effect. The plant is named in
      Iran as Tatoore. Symptoms and signs of acute D. Stramonium poisoning usually are
      similar to anticholinergic syndrome. This study is done in order to clarify the
      status of this poisoning in our region. MATERIALS AND METHODS: This study is a
      case series on all patients admitted to Imam Reza Hospital, Mashhad, Iran, with
      acute D. Stramonium poisoning between 2008 and 2011. We observed their symptoms,
      signs, routine laboratory test results and treatment used to control their
      symptoms. RESULTS: There were 19 patients included in our study. Children were
      poisoned more commonly than teenagers and poisoning in adults was rare. All of
      the children ingested the plant accidentally. The most presenting symptom was
      irritability and the most common sign was sinus tachycardia. There was not any
      presentation of seizure or coma. Most of the symptoms were controlled by
      parenteral benzodiazepines and there were no need to use of cholinergic agents
      such as physostigmine. CONCLUSION: Our study showed most of D. Stramonium
      poisoned population in our region are children. We suggest decreasing
      accessibility to the plant in order to decrease the incidence of its poisoning.

PMID- 25050236
TI  - The effect of red grape juice and exercise, and their combination on
      parkinson(')s disease in rats.
AB  - OBJECTIVE: Parkinson(')s disease (PD) is one of the most common neurodegenerative
      disorders which is characterized by tremor, rigidity, bradykinesia and postural
      disturbances. Studies indicate that grape juice and exercise may have beneficial
      effects on neurodegenerative disorders. Therefore, in the present study, we
      evaluated the effects of red grape juice (GJ) together with treadmill running on
      animal model of PD. Materials and Methods : 30 male Wistar rats were divided
      randomly into Sham, PD, PD treated with GJ (PD-GJ), PD treated with exercise (PD
      Ex), and PD treated with GJ associated with exercise (PD-GJ-Ex) groups with six
      rats in each. In order to obtain the PD model, 6-OHDA was infused into left
      substantia nigra pars compacta. In order to prove that the lesions are created
      and to estimate their extent, apomorphine was administered (i.p.) and total
      number of induced rotations was recorded during 60 minutes. Exercise was applied
      by treadmill and GJ was added into drinking water for 30 days and rotations test
      was performed again. RESULTS: Our results indicate that there was a significant
      difference in number of rotations between PD and Sham groups (p<0.05). At the end
      of experiment, number of rotations decreased significantly in both PD-GJ and PD
      GJ-Ex groups (p<0.05). Exercise alone increased the number of rotations non-
      significantly. CONCLUSION: Grape juice reduced rotations probably via the
      antioxidant agents.

PMID- 25050237
TI  - Crocin alleviates the local paw edema induced by histamine in rats.
AB  - OBJECTIVE: Crocin, as an active constituent of saffron, has many biological
      functions including antioxidant and anti-inflammatory activities. The present
      study was aimed to investigate the effects of crocin and chlorpheniramine on
      local edema induced by histamine. MATERIALS AND METHODS: Local edema was induced
      by subcutaneous injection of histamine (100 MUl, 0.1%) in ventral surface of
      right hind paw. The thickness of paw was measured at 1 h before and 1, 2, 3 h
      after injection of histamine, using a fine caliper. The number of neutrophils in
      paw tissue sections was counted 3 h after intraplantar injection of histamine.
      RESULTS: Intraperitoneal injection of crocin at doses of 100 and 200 mg/kg and
      chlorpheniramine at a dose of 10 mg/kg significantly (p<0.05) decreased both paw
      thickness and infiltration of neutrophils in paw tissues. In a combined
      treatment, intraperitoneal injection of an effective dose of crocin (100 mg/kg)
      with an ineffective dose of chlorpheniramine (2.5 mg/kg) produced a more
      documented response in comparison with crocin (100 mg/kg) and chlorpheniramine
      (2.5 mg/kg) used alone. CONCLUSION: The results suggested that both crocin and
      chlorpheniramine suppressed histamine-induced local paw edema. Moreover,
      histamine H1 receptors function may be affected by crocin.

PMID- 25050238
TI  - Taxonomic evaluation of misidentification of crude herbal drugs marketed in Iran.
AB  - OBJECTIVE: Medicinal plants organize an effective source of folk and modern
      medicine. Correct identification, authentication and quality control are
      essential to ensure safety, therapeutic potency, efficacy and reproducible
      quality of herbal medicines. The aim of this study is to use taxonomic method for
      authentication of traditional herbal drugs which are commonly sold in herbal
      shops in Iran. In this regard, twenty-seven cases of herbal drugs suspected to be
      adulterated were investigated. MATERIAL AND METHODS: Crude raw material of herbal
      drugs was prepared from the various markets in Iran and was identified at the
      Ferdowsi University of Mashhad Herbarium (FUMH). RESULTS: Taxonomic evaluation
      revealed that 78 species belonging to 21 families which are traded in Iranian
      market should be considered as authentic, adulterated and substituted samples.
      CONCLUSION: It was concluded that nowadays, many of the medicinal plants
      available in the market have ambiguous identification along with adulteration and
      contamination. The present study provides awareness amongst the traders,
      researchers, clinicians and manufacturing units about the ambiguity of
      authenticity in the traded herbal raw materials.

PMID- 25050239
TI  - The antioxidant and Flavonoids contents of Althaea officinalis L. flowers based
      on their color.
AB  - OBJECTIVE: There has been a growing interest in finding plants with biological
      active ingredients for medicinal application. MATERIALS AND METHODS: Three colors
      of petals of Althaea officinalis (A. officinalis) flowers, i.e., pink, reddish
      pink, and white were examined for total antioxidant activity and flavonoids
      content. RESULTS: The reddish pink flowers of A. officinalis have more
      antioxidant activity and the power of antioxidant activity was reddish pink >
      pink > white. CONCLUSION: Findings suggest that the dark color can serve as an
      indicator of antioxidant content of the plant. Flavonoid content was highest in
      white flower thus this result indicated that flowers with light color can be
      considered for medicinal uses.

PMID- 25050240
TI  - Antibacterial activity of Glycyrrhiza glabra against oral pathogens: an in vitro
      study.
AB  - OBJECTIVES: Oral infections and dental caries are still considered as serious
      public health problems and inflict a costly burden to health care services around
      the world and especially in developing countries. MATERIALS AND METHODS: In the
      present study, we evaluated the antibacterial activity of Glycyrrhiza glabra (G.
      glabra) against oral pathogens by diffusion methods and determined the minimum
      inhibitory concentration (MIC) by both broth and Agar dilution methods and
      minimum bactericidal concentration (MBC) by broth dilution methods. RESULTS: In
      this study, G. glabra extract showed good antibacterial activity against six
      bacteria. No strain in this study showed resistance against this extract.
      CONCLUSION: G. glabrais suggested as an appropriate candidate to help us in order
      to control dental caries and endodontic infections.

PMID- 25050241
TI  - Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation
      induced DNA damage in PC12 cells.
AB  - OBJECTIVE: The discovery and development of natural products with potent
      antioxidant properties has been one of the most interesting and promising
      approaches in the search for treatment of CNS injuries. The most significant
      consequence of the oxidative stress is thought to be the DNA modifications, which
      can become permanent via the formation of mutations and other types of genomic
      instability resulting cellular dysfunction. Serum/glucose deprivation (SGD) has
      served as an excellent in vitro model for the understanding of the molecular
      mechanisms of neuronal damage during ischemia and for the development of
      neuroprotective drugs against ischemia-induced brain injury. Nigella sativa (N.
      sativa) seeds and thymoquinone (TQ), its most abundant constituent, have been
      shown to possess anti-inflammatory, antioxidant, chemopreventive and anti
      neoplastic effects both in vitro and in vivo. Therefore, in this study we
      investigated genoprotective effects of N. sativa and TQ on DNA damage of PC12
      cells under SGD condition. MATERIALS AND METHODS: PC12 cells were cultured in
      DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and
      100 ug/ml streptomycin. Initially cells were pretreated with different
      concentrations of N. sativa extract (NSE), (10, 50, 250 ug/ml) and TQ (1, 5, 10
      ug/ml) for 6 h and then deprived of serum/glucose (SGD) for 18 h. The alkaline
      comet assay was used to evaluate the effect of these compounds on DNA damage
      following ischemic insult. The amount of DNA in the comet tail (% tail DNA) was
      measured as an indicator of DNA damage. RESULTS: A significant increase in the %
      tail DNA was seen in nuclei of cells following SGD induced DNA damage (p<0.001).
      In the control groups, no significant difference was found in the % tail DNA
      between NSE- or TQ-pretreated and vehicle-pretreated PC12 cells (p>0.05). NSE and
      TQ pretreatment resulted in a significant decrease in DNA damage following
      ischemic insult (p<0.001). This suppression of DNA damage by NSE and TQ was found
      to be dose-dependent. CONCLUSION: These data indicate that NSE and TQ have a
      genoprotective property, as revealed by the comet assay, under SGD condition in
      PC12 cells.

PMID- 25050242
TI  - New sesquiterpene coumarin from the roots of Ferula latisecta.
AB  - OBJECTIVE: The genus of Ferula belongs to the tribe Peucedaneae, subfamily of
      Apioideae and family of Umbelliferae with 133 species distributed throughout the
      Mediterranean area and central Asia, especially in the former USSR and
      neighboring countries such as Iran. The popular Persian name of the most of these
      species is "Koma". In this research we tried to isolate and elucidate the
      structure of new sesquiterpene in the root of Ferula latisecta (F. latisecta).
      MATERIALS AND METHODS: Dried and powdered roots of F. latisecta were extracted
      with CH2Cl2 using a Soxhlet apparatus. The extract was concentrated in vacuo to
      give a red extract. The extract was subjected to column chromatography on silica
      gel. (1)H NMR, (13)C NMR, DEPT, (1)H-(1)H COSY, HMBC, HSQC, and NOESY spectra
      were the methods we used to elucidate the structure of new sesquiterpene in this
      plant. RESULTS: One new sesquieterpene coumarin, namely Latisectin and IUPAC name
      [1-(2-Hydroxy-4-methoxy-phenyl)-3,4,8,12-tetramethyl-trideca-4,7,11-trien-1-one ]
      , together with one known compound , Kopetdaghin C, were isolated from the root
      of F. latisecta. CONCLUSION: In this research the structure of one new and one
      known sesquiterpene in the root of F. latisecta was elucidated.

PMID- 25050243
TI  - Evaluation of antioxidant activity of Malus domestica fruit extract from Kashan
      area.
AB  - OBJECTIVE: Antioxidants are considered as the main factors in the inhibition of
      unwanted oxidation reactions. MATERIALS AND METHODS: In this research the
      antioxidant potential of the fresh fruits of 4 cultivars (A to D) of Malus
      domestica (M. domestica) cultivated in the Kashan, Qamsar area was evaluated. The
      antioxidant activity of the samples were evaluated using two complementary
      antioxidant assays: 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and beta
      carotene/linoleic acid tests and the results were compared with the synthetic
      standard antioxidant butylated hydroxytoluene (BHT). RESULTS: Total phenolic
      contents of the samples are also estimated by Folin-Ciocalteu's phenol test. In
      both DPPH beta-carotene/linoleic acid tests in the concentration of 2 mg/ml, only
      samples from cultivar A showed moderate antioxidant activity with 63.92+/-0.42
      and 6.02+/-0.03 inhibition percentages, respectively and other samples were
      weakly active. CONCLUSION: The Folin-Ciocalteu's phenol test was also showed very
      little phenolic compounds for the fruits. In conclusion, weak antioxidant
      activity was estimated for the studied apple cultivars.

PMID- 25050244
TI  - The effects of Carthamus tinctorius L. on placental histomorphology and survival
      of the neonates in mice.
AB  - OBJECTIVE: Carthamus tinctorius L. (Safflower) is a member of the asteraceae
      family which is used as a food additive but also has medicinal applications. This
      study investigated its effects on placental histomorphology and survival of mice
      neonates. MATERIALS AND METHODS: Eighty Balb/C pregnant mice were randomly
      distributed into one control and three experimental groups (n=20). The control
      group received only distilled water, whereas experimental groups were
      administered intraperitoneally C. tinctorius extract at doses of 0.7, 1.4, and
      2.8 mg/kg during the organogenesis period (6(th) to 16(th) day of gestation). On
      the 17(th) day of gestation, half of the animals were euthanized; their fetuses
      and placentas were removed and histomorphological study was performed. In the
      rest of the animals after parturition, the number of neonates was counted.
      Survival rates were periodically calculated for neonates within days 5, 15, 25,
      and 42 after birth. The results were evaluated by one-way ANOVA. RESULTS: The
      results showed that treatment with 1.4 and 2.8 mg/kg C. tinctorius extract caused
      reduction in the trophoblastic giant cells ratio and increasing in the proportion
      of labyrinthine interhemal membrane (LIM). Moreover, the size of the labyrinthine
      zone per whole placenta, weight, diameter, and thickness of the placenta in the
      mice administered with 1.4 and 2.8 mg/kg C. tinctorius extract became lower than
      those of controls (p<0.05). In addition, in the treated mice with 1.4 and 2.8
      mg/kg C. tinctorius extract, the number of neonate was drastically decreased on
      days 5, 15, 25, and 42 after birth. CONCLUSION: It is concluded that treatment
      with C. tinctorius extract in doses of 1.4 and 2.8 mg/kg induces toxic changes in
      the placental structure so caution should be paid to popular consumption of this
      plant both as an alternative medicine and as a food additive.

PMID- 25050245
TI  - Evaluation of the effects of hydroalcoholic extract of Berberis vulgaris root on
      the activity of liver enzymes in male hypercholesterolemic rats.
AB  - OBJECTIVES: Hyperlipidemia can cause a variety of diseases such as
      atherosclerosis, diabetes, and fatty liver which is followed by increased liver
      enzymes. Since Berberis vulgaris (B. vulgaris) root possesses antioxidant
      properties, the present study was conducted to investigate the effect of its
      extract on the activity of liver enzymes in rats. MATERIALS AND METHODS: In this
      experimental study, sixty Wistar rats were selected and allocated to six groups
      of ten each. The control group received a normal diet and the sham group received
      a fatty diet while the other groups including experimental groups received a
      fatty diet and the alcoholic extract of B. vulgaris at minimum (75 mg/kg),
      moderate (150 mg/kg), and maximum (300 mg/kg) doses by intraperitoneal injection
      (i.p.) or oral atorvastatin (10 mg /kg) with a fatty diet. At the end of this 21
      day period, blood samples were drawn and the levels of the intended factors were
      measured. Data were analyzed using SPSS software version 11.5. RESULTS: The
      comparison of the obtained results showed that the levels of alanine transaminase
      (ALT) and alkaline phosphatase (ALP) enzymes in the sham group that only received
      fatty food increased (p<=0.05), whereas in the treatment groups receiving B.
      vulgaris extract as well as in the group receiving Atorvastatin, these enzymes
      significantly decreased; however, no significant changes were observed in
      aspartate transaminase (AST) levels. CONCLUSION: Noticing the antioxidant
      properties of B. vulgaris root extract and its effects on reducing the activity
      of liver enzymes, the extract of this plant can be a good choice for improving
      the function of liver.

PMID- 25050246
TI  - Neuro-pharmacological effects of Crinum zeylanicum in mice.
AB  - OBJECTIVES: The aim of present study was to evaluate some effects of Crinum
      zeylanicum (C. zeylanicum) on central nervous system. MATERIALS AND METHODS: C.
      zeylanicum methanolic bulb extract (250-1000 mg/kg orally), 2 mg chlorpromazine
      and 4 mg diazepam /kg body weight intraperitoneally respectively were tested in
      mice using Irwin test, pentobarbitone-induced sleep test, spontaneous motor
      activity, apomorphine-induced stereotype behaviour, and rota-rod performance.
      RESULTS: The C. zeylanicum bulb extract significantly and dose-dependently
      decreased apomorphine-induced hyperactivity in mice (p<0.001). The Irwin test
      revealed dose-dependent central depressant effect of the extract, shortened
      (p<0.05-0.01) the onset of sleep and prolonged the duration of sleep. The extract
      produced significant (p<0.05-0.001) and dose- dependent reduction in spontaneous
      motor activity and apomorphine-induced stereotype behaviours in mice. The extract
      had no effect on performance of mice on rotarod. CONCLUSION: The results suggest
      that the extract may possess sedative principles with potential neuroleptic
      properties.

PMID- 25050247
TI  - Phytochemical study of polyphenols in Perilla Frutescens as an antioxidant.
AB  - Perilla frutescens is an annual herb of the mint family native to East Asia.
      Polyphenols present in perilla have various structural varieties with large
      diversity of biological activities. It is direct influence the quality of perilla
      plant and their potential functions. Some of these products have been studied and
      proven to be effective source of phenolic antioxidants. The aqueous extract
      contains phenolic compounds such as phenolic acids, cinnamic acid derivatives,
      flavonoids, and lignans. Gallic acid, hydroxytyrosol (3,4-DHPEA), cinnamic acid
      derivatives (coumaroyl tartaric acid, caffeic acid and rosmarinic acid),
      flavonoids, scutellarein 7-O-diglucuronide, luteolin 7-O-diglucuronide, apigenin
      7-O-diglucuronide, luteolin 7-O-glucuronide, and scutellarein 7-O-glucuronide),
      and anthocyanins (mainly cis-shisonin, shisonin, malonylshisonin and cyanidin 3-O
      (E)-caffeoylglucoside-5-O-malonylglucoside) are present. 

PMID- 25050248
TI  - Hydro-alcoholic extract of the root of Prangos ferulacea (L.) Lindl can improve
      serum glucose and lipids in alloxan-induced diabetic rats.
AB  - OBJECTIVES: Diabetes mellitus manifests itself in a wide variety of complications
      and the symptoms of this disease are multifactorial. Previous studies proved that
      this disease is directly related to hyperglycemia and hyperlipidemia. The aim of
      this study was to investigate the hypoglycemic and hypolipidemic effects of
      hydroalcoholic extract of Prangos frulacea (L.) Lindl in alloxan-induced diabetic
      rats. MATERIALS AND METHODS: Forty female Wistar rats with body weight of 200+/
      20 g were randomly divided into five groups with eight rats per group. Diabetes
      was induced in rats by alloxan monohydrate at dose of 120 mg/kg body weight (BW)
      injected intraperitoneally. Hydro-alcoholic extract of the root and leaves with
      stems of P. frulacea at 100 mg/kg BW were given orally to diabetic rats daily for
      4 weeks. RESULT: Diabetic rats (D) exhibited a significant (p<0.05) increase in
      the levels of the serum glucose, Total Cholesterol (TC), Triglycerides (TG), and
      LDL in comparison with the control group whereas their BW and serum HDL levels
      were decreased. In diabetic rats treated by root extract of P. frulacea, these
      parameters were reversed to the normal levels compared with diabetic group.
      CONCLUSION: According to the results obtained, it was concluded that Root's hydro
      alcoholic extract of P. frulacea can be used in diabetics for the purpose of
      glucose and lipid profile reduction.

PMID- 25050249
TI  - A cytotoxicity and comparative antibacterial study on the effect of Zataria
      multiflora Boiss, Trachyspermum copticum essential oils, and Enrofloxacin on
      Aeromonas hydrophila.
AB  - OBJECTIVE: this study designed to test the antibacterial potency of enrofloxacin
      (ENR) and essential oils from Zataria multiflora Boiss (ZEO) and Trachyspermum
      copticum (TEO) on Aeromonas hydrophila. MATERIAL AND METHODS: The antibacterial
      potency of test compounds was determined by several methods including the
      inhibition zone diameter determination, microbroth dilution method and
      colorimetric method of MTT. The cytotoxicity of test substances was assessed on
      Chinook salmon (Oncorhynchus tshawytscha) embryo (CHSE-214) cells. RESULTS:
      RESULTS showed that ENR and tested essential oils exert antibacterial effect
      against A. hydrophila. Moreover, ENR exerted the most potent antibacterial effect
      with MIC values of 62.5 ng/ml. The natural compounds of ZEO and TEO also showed
      antibacterial effects with rather high MIC values of 0.315 mg/ml, and 1.25 mg/ml,
      respectively. None of the tested substances showed toxicity on CHSE-24 cells.
      CONCLUSION: It is concluded that ZEO and TEO could be applied to prevent from A.
      hydrophila infection. Moreover, data also suggest that MTT method could be both
      cost- and time-effective and accurate method of MIC determination.

PMID- 25050250
TI  - Effect of curcumin, the active constituent of turmeric, on penicillin-induced
      epileptiform activity in rats.
AB  - OBJECTIVE: Curcumin is a major constituent of turmeric and has many biological
      functions such as anticancer and anti-inflammatory effects. The present study was
      conducted to investigate the effects of curcumin and diazepam in separate and
      combined treatments on penicillin-induced seizures in rats. MATERIALS AND
      METHODS: In urethane-anesthetized rats, epileptiform activity was induced by
      intracortical (i.c.) administration of penicillin (200 IU, 1 ul), and frequency
      and amplitude of spike waves were analyzed using electrocorticographic
      recordings. RESULTS: Intraperitoneal (i.p.) injections of curcumin at doses of
      100 and 200 mg/kg, and intracerebroventricular (i.c.v.) injection of diazepam at
      a dose of 5 ug significantly (p<0.05) reduced both frequency and amplitude of
      spike waves. Co-administrations of curcumin (50 mg/kg, i.p.) with diazepam (5 ug,
      i.c.v) enhanced the antiepileptic effect of diazepam (5 ug, i.c.v). CONCLUSION:
      The results suggested that both curcumin and diazepam suppressed penicillin
      induced epileptiform activity. A potentiation effect was observed between
      curcumin and diazepam in reducing penicillin-induced seizures.

PMID- 25050251
TI  - Effect of natural honey from Ilam and metformin for improving glycemic control in
      streptozotocin-induced diabetic rats.
AB  - OBJECTIVE(S): Diabetes mellitus is a public health problem and one of the five
      leading causes of death globally. In the present study, the effect of Metformin
      with natural honey was investigated on glycemia in the Streptozotocin-induced
      diabetic rats. MATERIALS AND METHODS: Thirty Wistar male rats were randomly
      divided into six groups including C: non diabetic rats received distilled water,
      CH: non diabetic rats received honey, CD: diabetic rats administered with
      distilled water, DM: Metformin treated diabetic rats, DH: honey treated diabetic
      rats, and DMH: diabetic rats treated with a combination of Metformin and natural
      honey. Diabetes was induced by a single dose of Streptozotocin (65 mg/kg; i.p.).
      The animals were treated by oral gavage once daily for four weeks. At the end of
      the treatment period, the animals were sacrificed and their blood samples
      collected. Amount of glucose, triglyceride (TG), total cholesterol (TC), HDL
      cholesterol, LDL cholesterol, VLDL cholesterol, total bilirubin, and albumin were
      determined in serum. RESULTS: Group CD: showed hyperglycemia (252.2+/-4.1 mg/dl),
      while level of blood glucose was significantly (p<0.01) reduced in groups DH
      (124.2+/-2.7 mg/dl), DM (108.0+/-3.4 mg/dl), and DMH (115.4+/-2.1 mg/dl). Honey
      in combination with Metformin significantly (p<0.01) reduced level of bilirubin
      but Metformin alone did not reduce bilirubin. Honey alone and in combination with
      Metformin also significantly reduced triglycerides, total cholesterol, LDL, VLDL
      and increased HDL, but Metformin did not reduced triglycerides and increased HDL.
      CONCLUSION: The results of the present study demonstrated that consuming natural
      honey with Metformin improves glycemic control and is more useful than consuming
      Metformin alone. The higher therapeutic effect of Ilam honey on lipid
      abnormalities than Tualang honey was also evident.

PMID- 25050252
TI  - Motor disturbances and thalamic electrical power of frequency bands' improve by
      grape seed extract in animal model of Parkinson's disease.
AB  - OBJECTIVE: Previous studies showed that grape seed extract (GSE) is an excellent
      natural substance with potent antioxidant effect and free radical scavenger. This
      study aimed to evaluate the effect of GSE on motor dysfunctions and thalamic
      local Electroencephalography (EEG) frequency bands' powers in rats with
      Parkinson's disease (PD). MATERIALS AND METHODS: In this study 8 ug 6
      hydroxydopamine (6-OHDA) dissolved in 2 ul normal saline containing 0.01%
      ascorbic acid was infused into right medial forebrain bundle (MFB) to make an
      animal model of PD. Rats with PD received four weeks GSE (100 mg/kg, p.o.) after
      apomorphine-induced rotation test. Spontaneous motor tests and also thalamic
      ventroanterior nucleus (AV) local EEG recording were done in freely moving rats
      in all groups. RESULTS: Chronic treatment of PD rats with GSE could influence
      potentially frequency bands' powers of thalamic VA and improve post-lesion motor
      dysfunctions significantly (p<0.05 and p<0.01, respectively). CONCLUSION: Our
      findings suggest that GSE modulates the CNS function and has beneficial effects
      on the direct and indirect striato-thalamo-cortical pathways in PD. GSE acts as a
      new and potent natural free radical scavenger which removes oxidants produced by
      neurotoxin 6-OHDA in brain. Therefore, it reinforces electrical power of remained
      thalamic VA neurons and thereby improves post-lesion motor disorders.

PMID- 25050253
TI  - Extract of Adenanthera pavonina L. seed reduces development of diabetic
      nephropathy in streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: The aim of the present study was to investigate the renal protective
      effect of Adenanthera pavonina (A. pavonina) seed aqueous extract (APSAE), in
      streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The renal
      protective effect of A. pavonina seed aqueous extract (APSAE) was studied in STZ
      induced diabetic rats. APSAE (50, 100 and 200 mg/kg per day) was given daily to
      diabetic rats for 13 weeks. Blood glucose, serum parameters such as albumin,
      creatinine, total protein, urea, lipid profile, glycated haemoglobin (HbA1c), and
      urine parameters such as urine protein and albumin were examined. Kidney
      histopathology was also done. RESULTS: After 13 weeks of treatment, in STZ
      induced diabetic rats, severe hyperglycemia was developed, with marked increase
      in proteinuria and albuminuria. However, APSAE treatment significantly reduced
      proteinuria, albuminuria, lipid levels, and HbA1c deposition in diabetic rats.
      CONCLUSION: These results suggested that APSAE has reduced development of
      diabetic nephropathy in streptozotocin-induced diabetic rats and could have
      beneficial effect in reducing the progression of diabetic nephropathy.

PMID- 25050254
TI  - Evaluation of antimicrobial activity of Malus domestica fruit extract from Kashan
      area.
AB  - OBJECTIVE: Many species of plants present noticeable potency against human
      bacterial and fungal pathogens. MATERIALS AND METHODS: In the current study,
      antimicrobial activity of the fresh fruits of 4 cultivars (A to D) of Malus
      domestica cultivated in the Qamsar area of Kashan, Iran was investigated. The
      disk diffusion and minimal inhibitory concentration (MIC) evaluation
      antimicrobial activity tests were performed. RESULTS: The samples showed moderate
      antimicrobial activities with inhibition zones from 11 to 16 mm in these tests.
      Cultivar D with inhibition zones of 16, 14, and 12 mm for E. coli, S. epidermidis
      and K. pneumoniae, respectively exhibited the best results in these tests.
      Cultivar A also showed a zone of inhibition of 11 mm against P. aerouginosa.
      CONCLUSION: Moderate antimicrobial activities were observed for the studied apple
      cultivars.

PMID- 25050255
TI  - In vitro capacity and in vivo antioxidant potency of sedimental extract of
      Tinospora cordifolia in streptozotocin induced type 2 diabetes.
AB  - OBJECTIVE: The role of herbs against the free radicals have been put forth
      recently in combating many diseases. The aim of this study was to elucidate the
      in vitro capacity and in vivo antioxidant properties of sedimental extract of
      Tinospora cordifolia (SETc). MATERIALS AND METHODS: SETc was subjected to in
      vitro chemical analysis such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric
      oxide, hydrogen peroxide, and superoxide anion radicals scavenging respectively
      and finally drugs reductive ability in order to elucidate the antioxidant
      capacity of the test drug before introducing it into the biological membrane. The
      resulting capacity was evaluated in vivo by analyzing enzymic (SOD, CAT) and non
      enzymic (vitamin C & E) antioxidant levels in the homogenized samples of major
      organs isolated from streptozotocin induced type 2 diabetic rats after 30(th) day
      of SETc (1000 mg/kg/p.o.) treatment. Finally, the histopathological evaluation
      was done using cut portion of the respective organs prone to free radical
      mediated cell destruction with STZ in order to study their micro anatomical
      changes. RESULTS: Chemical analysis with SETc in vitro for its IC50 proves a key
      evident for its total antioxidant capacity of around 2046 times, in 1000 mg/kg of
      fixed dose per oral for in vivo analysis. In contrast to the above, the lipid
      peroxide levels and in vivo enzymic and non-enzymic antioxidant levels were found
      to possess most significant difference (p<0.001) and moderate difference (p<0.01)
      with diabetic non-treated animals which was an supporting contribution for those
      in vitro parameters studied and have proved that SETc (1000 mg/kg/p.o.) was a
      potent drug to elevate the antioxidants levels and further healing of damaged
      organs as compared with that of diabetic and standard drug treated groups.
      CONCLUSIONS: Finally, it was concluded that, the presence of antioxidant
      potentials in SETc was about 2046 time as an effective scavenger of free radicals
      in vitro and as a potent healer in ameliorating many signs of tissue damages in
      vivo in long term complicated diseases such as diabetes.

PMID- 25050256
TI  - Antioxidant activities of two sweet pepper Capsicum annuum L. varieties phenolic
      extracts and the effects of thermal treatment.
AB  - OBJECTIVES: Sweet peppers Capsicum annuum L. (C. annuum) are an excellent source
      of vitamins A and C as well as phenolic compounds, which are important
      antioxidant components that may reduce the risk of diseases. The objective of
      this study was to evaluate their antioxidant activity under various temperatures.
      MATERIALS AND METHODS: To compare the antioxidant activity in various
      temperatures (20, 35, 50, and 65  degrees C), two different types of colored (red
      and green) sweet bell peppers C annuum were selected. The red peppers were
      selected from those cultivated in Shahreza, Esfahan and the green peppers with
      the local name of Gijlar were selected from those cultivated in Urmia, West
      Azarbayjan. The experiments were carried out to measure the total phenolic and
      flavonoid content, ferric reducing antioxidant power (FRAP), chain-breaking
      activity, scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), and
      hydrogen peroxide radicals. RESULTS: Total phenol and flavonoid contents of
      pepper extracts were enhanced with increasing temperature to 65  degrees C.
      Scavenging capacity of DPPH radical of red pepper extract was enhanced because of
      putting at 50  degrees C for 30 min and for Gijlar pepper extract scavenging
      capacity was increased at 65  degrees C. Scavenging capacity of hydrogen peroxide
      radical of extracts was the highest at 35  degrees C. Chain-breaking activity of
      red pepper extract was increased for 60 min at 35  degrees C. FRAP (C) of red
      pepper extract was significantly different (p<0.05) in compare with Gijlar
      pepper. CONCLUSION: An appropriate temperature maintained a high antioxidant
      activity of phenolic compound, which could be due to the combined effect of non
      enzymatic reaction and phenolic compound stability.

PMID- 25050257
TI  - Cellular antioxidative, cytotoxic, and antileishmanial activities of Homalium
      letestui.
AB  - OBJECTIVE: Homalium letestui Pellegr (Flacourtiaceae) is used in traditional
      medicine in parts of Nigeria for the treatment of malaria, ulcer, and
      inflammatory diseases and as an aphrodisiac. This investigation was aimed to
      evaluate the cytotoxic, immunomodulatory, and antileishmanial properties of stem
      extract and fractions of Homalium letestui (H. letestui). MATERIALS AND METHODS:
      Cytotoxic activity against HeLa cells was done using sulphorhodamine (SRB) method
      and DNA interaction activity using gel electrophoresis. Immunomodulatory activity
      of the extract in whole blood, neutrophils, and macrophages was also investigated
      using luminol/lucigenin-based chemiluminescence assay. The extract and fractions
      were similarly screened for antileishmanial activity against promastigotes of
      Leishmania major in vitro. The GCMS analysis of the most active fraction against
      HeLa cells was carried out. RESULTS: The stem extract exerted prominent cytotoxic
      activity with the dichloromethane fraction exhibiting the most pronounced effect
      (GI50 -5.12+/-1.45 ug/ml, LC50- 57.3+/-2.33 ug/ml, TGI -12.6+/-0.87 ug/ml). The
      crude extract and the fractions did not interact with DNA when investigated using
      electrophoresis. The extract significantly ((p<0.05 - 0.001) inhibited oxidative
      burst activity in whole blood (-27.90-66.90%), isolated polymorphonuclear cells
      (PMNs) (16.50-67.0%), and mononuclear cells (MNCs) (4.31-98.50%) when two
      different phagocytosis activators (serum opsonizing zymosan-A and PMA) were used.
      The extract also exhibited moderate antileishmanial activity against
      promastigotes of Leishmania major in vitro. GCMS analysis of active fraction
      revealed pharmacologically active compounds. CONCLUSION: These results suggest
      that the stem extract/fractions of H. letestui possess cytotoxic,
      immunomodulatory, and antileishmanial activities.

PMID- 25050259
TI  - The preventive effect of Brassica napus L. oil on pathophysiological changes of
      respiratory system in experimental asthmatic rat.
AB  - OBJECTIVE: Asthma is an airway complex disease defined by reversible airway
      narrowing and obstruction, chronic airway inflammation, airway
      hyperresponsiveness, and tissue remodeling. The purpose of this study was to
      determine the effect of Brassica napus L. (B. napus) on airway pathologic changes
      in a rat model of asthma. MATERIALS AND METHODS: Twenty-four rats were divided
      into 4 groups: control, asthmatic, asthmatic treated with 0.5 mg/kg B. napus oil,
      and asthmatic treated with 0.75 mg/kg B. napus oil. To induce the experimental
      asthma, rats in groups 2, 3, and 4 received an i.p. injection of ovalbumin and
      aerosolized ovalbumin. Simultaneously, rats in groups 3 and 4 received B. napus
      oil daily by gavage. After 31 days, in all groups, thoracotomy was done and lung
      tissue samples were taken. For pathological evaluation, microscopic slides were
      prepared. The eosinophil numbers in the submucosal layer and thicknesses of
      smooth muscle layer of bronchioles were detected. RESULTS: Eosinophil numbers in
      the submucosal layer, as well as smooth muscle layer thicknesses were
      significantly lower in the rat group treated with 0.75 mg/kg B. napus oil as
      compared with asthmatic group (p<0.01, p<0.05). CONCLUSION: B. napus could be
      useful as adjuvant therapy in rat model of asthma. This effect was probably
      related to its antioxidants components that reduce the levels of inflammatory
      mediators such as leukotrienes, IL-4, IL-5, and IL-13.

PMID- 25050258
TI  - Effects of fresh, aged and cooked garlic extracts on short- and long-term memory
      in diabetic rats.
AB  - OBJECTIVE: The present study was hypothesized to investigate the beneficial
      effects of fresh, aged, and cooked garlic extracts on blood glucose and memory of
      diabetic rats induced by streptozocine (STZ). MATERIAL AND METHODS: Diabetes was
      induced by an intraperitoneal injection of STZ (60 mg/kg body weight). An oral
      dose of 1000 mg/kg of each garlic extract was given daily for 4 weeks after
      diabetes induction. Five days after STZ injection, five groups were formed:
      Control (intact) rats (Cont) + Vehicle of garlic extract (normal saline) (Veh),
      STZ + Veh, STZ + Fresh (row) garlic (FG), STZ + Aged garlic (AG), and STZ +
      cooked (boiled) garlic (CG). In order to assess the passive avoidance memory,
      rats were gently placed on the wooden platform, and latency to step-down (SDL)
      was recorded as initial phase, after then a light electrical shock [0.3 mA, 3
      sec, Alternative current (AC)] was delivered to their foot paw. The retrieval
      tests were done for short- and long-term memories, respectively. Blood glucose
      was assayed by glucometer before and after treatment with STZ and garlic
      extracts. RESULTS: Hyperglycemia induced by STZ decreased short-term memory in
      both diabetic males and females rats significantly compared with the controls
      (p<0.001 and p<0.01). Fresh and cooked but not aged garlic extracts decreased
      blood glucose in diabetic males and increased memory in both diabetic male and
      female rats significantly (p<0.05 and p<0.01). CONCLUSIONS: STZ causes elevation
      of the blood glucose and resulted in memory deficits, possibly viafree radicals
      production in brain tissue. Garlic has some bioactive chemicals including allicin
      and sulfur compound (OSC) which could lower the blood glucose during chronic
      hyperglycemia, inhibit free radicals production in brain, and improve short-term
      (but not long-term) memory.

PMID- 25050260
TI  - An ethnobotanical survey on hormozgan province, Iran.
AB  - OBJECTIVE: The present study is based on an ethnobotanical research project
      conducted in Hormozgan province that is located in south of Iran, bordering
      waters of the Persian Gulf and Oman Sea. This survey was carried out in order to
      recover the ethnobotanical and ethnomedicinal knowledge of the residents of this
      province. They are using medicinal and functional plants for treating or
      preventing several diseases. MATERIALS AND METHODS: Ethnobotanical data sheets
      were run with the native inhabitants and people of the province by arranging
      frequent field trips to different parts of the province and direct interviews
      with them especially those who were more familiar with the plants and their
      usage. RESULTS: A total of 150 plant species belonging to 53 families were
      recorded for their ethnobotanical and ethnomedicinal uses among the people of
      province. The records were developed by scientific names, family names, local
      names, medicinal parts used, different ways of their application, and traditional
      uses of the plants. There was high compliance in the use of plants in painful
      disorders, gastrointestinal, and dermatological diseases. CONCLUSION: This study
      revealed that the people of Hormozgan province have a rich knowledge of natural
      resources. The use and consumption of medicinal plants are still important parts
      of their life. Rational use of native medicinal plants may benefit and improve
      their living standards and quality of life. The results of this study can be used
      as a basis for selecting herbs for further pharmacological, phytochemical, and
      pharmacognostical studies.

PMID- 25050261
TI  - Aqueous extract of Berberis integerrima root improves renal dysfunction in
      streptozotocin induced diabetic rats.
AB  - OBJECTIVE: Barberry root extract contains various alkaloids that are considered
      as antioxidants. Beneficial effect of aqueous extract of Berberis integerrima
      root (AEBIR) was evaluated for renal function in diabetic rats induced by STZ.
      MATERIAL AND METHODS: Diabetes was induced by i.p. injection of streptozotocin
      (65 mg/kg bw) to rats, after 15 h of fasting. Diabetic rats were randomly grouped
      and treated daily with AEBIR and glibenclamide by gavage for 42 days. After 6
      weeks of study, all the rats were sacrificed and some biochemical parameters of
      serum and urine were measured and their kidneys tissues were processed for light
      microscopy. RESULTS: Streptozotocin induced a significant rise in fasting blood
      glucose, serum creatinine, blood urea nitrogen, urine glucose, urine protein,
      urine albumin, and water intake and a significant decrease in body weight, serum
      protein, urine urea, and urine creatinine. There was a significant restoration of
      these parameters to near normal after administration of the AEBIR and also by
      glibenclamide (0.6 mg/kg bw). The activity of the extract at dose of 500 mg/kg in
      all parameters except blood glucose and urine glucose was more than that of the
      standard drug, glibenclamide (0.6 mg/kg, p.o.). Histopathological changes of
      kidney samples were comparable with respective control. CONCLUSION: These results
      suggested that aqueous extract of Berberis Integerrima root improves renal
      dysfunction in streptozotocin-induced diabetic rats through controlling blood
      glucose and renal protective effects.

PMID- 25050262
TI  - The effect of hydroalcoholic extract of Coriandrum sativum on rat appetite.
AB  - OBJECTIVE: Losing weight in consequence of appetite loss can be a sign of a
      serious underlying condition. Currently, the most widely prescribed medication
      for anorexia is cyproheptadine hydrochloride. However, the clinical use of
      cyproheptadine hydrochloride is limited by its side effects. In Iranian
      traditional medicine, Coriandrum sativum stimulates the appetite. Therefore, the
      effect of Coriandrum sativum (coriander) hydroalcoholic extract was investigated
      on food intake in rats. MATERIAL AND METHODS: Thirty male Wistar rats were
      randomly divided into five groups. Two control groups were used, one group
      received 0.5 ml water per day (vehicle group), and another group did not receive
      anything (control group). The other 3 groups were daily treated by 50, 100 or 150
      mg/kg of coriander for 7 days, respectively. The daily amount of the food eaten
      by each rat was measured for 10 days. The amount of energy intake of each rat was
      also calculated for 7 days during the intervention. The difference in energy
      intake was calculated and compared between groups. RESULT: There was no
      significant change in energy intake between control and vehicle groups. The
      change in energy intake after treatment by 100 and 150 mg/kg of the extract was
      significantly higher than other groups (p=0.030 and p=0.007) CONCLUSION: This
      study indicated that coriander had positive effects on appetite of rats. Future
      studies are needed to evaluate the mechanisms of the effects of this plant on
      appetite.

PMID- 25050263
TI  - Effects of ethanolic extract of green tea on decreasing the level of lipid
      profile in rat.
AB  - OBJECTIVE: The aim of the present study was to elucidate the possible biochemical
      improving effect in lipid metabolic that may result from continuous treatment
      with Green Tea extract in normal albino rats and those rendered hyperlipidemic by
      long term supplementation of fat-enriched diet. MATERIALS AND METHODS: Fifty male
      albino rats aged six weeks with 200+/-10 g weight were randomly divided into five
      groups: Group A (negative control), groups B (positive control), Group C
      (treatment with drug), Group D (treatment with extract), and Group E (prevention
      with extract). All groups except Group A were received fat-enriched diet
      throughout the study. Group C received 25 mg/kg/day of the nicotinic acid from
      day 28 to the end of study. Group D was also treated with 100 mg/kg/day of the
      extract from day 28 to the end of study and finally group E was also treated with
      100 mg/kg/day of the extract from the start of the study to the end. Lipid levels
      were determined weekly. Data were expressed as mean+/-SEM which were calculated
      using SigmaPlot(r) software. The obtained data were statistically analyzed using
      Student's t-test. RESULTS: In group (D), total cholesterol, LDLc, HDLc, and
      triglyceride levels were significantly decreased by 33.3%, 30.2%, 40%,
      respectively, compared with the group C (p<0.001 ). There was no significant
      difference in lipid profile in group E through the study. Nicotinic acid in group
      C decreased the serum levels of all measured parameters (p<0.001). The body
      weight of animals in treated groups with extract (groups D & E) were decreased by
      8% (p<0.01). CONCLUSION: The results of this study demonstrated that the extract
      of green tea has a hyperlipidemic lowering effect.

PMID- 25050264
TI  - Investigating contact toxicity of Geranium and Artemisia essential oils on
      Bemisia tabaci Gen.
AB  - OBJECTIVE: Sweet potato whitefly, Bemisia tabaci Gen. (B. tabaci), is one of the
      most important pests of various greenhouse crops in Iran. Nowadays, chemical
      insecticides are broadly used for control of the pests that causes risk to
      consumer's health. For the first time, contact toxicity of Pelargonium roseum
      Andrews and Artemisia sieberi Besser essential oils on B. tabaci and its possible
      application against the whitefly was evaluated in 2012. MATERIALS AND METHODS:
      Essential oil with concentrations of 2500, 1250, 125, and 12 ppm were used.
      Infested leaves of greenhouse cucumber were treated by mentioned concentrations.
      After 24 hours, mortality of B. tabaci was recorded and compared after correcting
      by Abbot's formula. RESULTS: RESULTS showed that all concentrations of the
      essential oil could significantly reduce population of B. tabaci compared with
      the control treatment. Phytotoxicity of the treated leaves were recorded after
      24, 48, and 72 hours and compared with the control. Concentrations of 2500, 1250,
      and 125 ppm caused severe phytotoxicity on greenhouse cucumber leaves and
      therefore are not suitable for greenhouse application. Phytotoxicity of 12 ppm
      was relatively low. CONCLUSIONS: This data implicated suitable protective effects
      of the essential oils to the pest infestation. Therefore, essential oils
      distillated from Geranium and Artemisia could be applied to control B. tabaci in
      greenhouse cucumber at V/V 12 ppm.

PMID- 25050265
TI  - Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract
      of Piper betle leaves.
AB  - OBJECTIVE: The present study was designed to evaluate the antioxidant, analgesic,
      and anti-inflammatory activities of the methanolic extract of Piper betle leaves
      (MPBL). MATERIALS AND METHODS: MPBL was evaluated for anti-inflammatory activity
      using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was
      evaluated by hot plate, writhing, and formalin tests. Total phenolic and
      flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of
      total ROS generation, and assessment of reducing power were used to evaluate
      antioxidant potential of MPBL. RESULTS: The extract of MPBL, at the dose of 100
      and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot
      plate method whereas significantly (p<0.05) reduced the writhing caused by acetic
      acid and the number of licks induced by formalin in a dose-dependent manner. The
      same ranges of doses of MPBL caused significant (p<0.05) inhibition of
      carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH,
      ONOO(-), and total ROS scavenging method, MPBL showed good antioxidant
      potentiality with the IC50 value of 16.33+/-1.02, 25.16+/-0.61 , and 41.72+/-0.48
      ug/ml, respectively with a significant (p<0.05) good reducing power. CONCLUSION:
      The findings of the study suggested that MPBL has strong analgesic, anti
      inflammatory, and antioxidant effects, conforming the traditional use of this
      plant for inflammatory pain alleviation to its antioxidant potentiality.

PMID- 25050266
TI  - Phytochemical screening and evaluation of Monechma ciliatum (black mahlab) seed
      extracts as antimicrobial agents.
AB  - OBJECTIVE: Tribes in Nubia Mountains regions of Sudan used Monechma ciliatum
      seeds for common cold and other chest allergic conditions as a traditional
      medicine. The aim of this paper is to validate this traditional practice
      scientifically. MATERIALS AND METHODS: Monechma ciliatum seeds were screened for
      major phytochemical groups using standard methods. Different extracts were
      bioassayed in- vitro for their bioactivity to inhibit the growth of pathogenic
      bacteria and fungi. RESULTS: Phytochemical screening results showed the presence
      of flavonoids, tannins, triterpens, and anthraquinones. Staphylococcus aureus was
      found to be sensitive to both water extract with zones of inhibition 22 - 26 mm
      at concentrations of 50 and 100mg/ml and ethanol extract 17 mm at concentration
      of 100 mg/ml. The growth of Klebsiella pneumoniae was inhibited by ethanol
      extract with zones of inhibition equal to 16, 26, and 33 mm at concentrations of
      50, 100, and 150 mg/ml, respectively. Pseudomonas aeruginosa was insensitive to
      all extracts used. Similarly, all used fungi were found to be insensitive to
      extracts used. The minimum inhibitory concentrations of the extracts against
      microorganisms were ranged from 12.5 to 25 mg/ml. CONCLUSION: The findings of the
      current study support the traditional uses of the plant's seed in the therapy of
      respiratory tract infections caused by Staphylococcus aureus and Klebsiella
      pneumoniae.

PMID- 25050267
TI  - Effects of Foeniculum vulgare ethanol extract on osteogenesis in human
      mecenchymal stem cells.
AB  - OBJECTIVE: Osteoporosis or silent disease is a major bone disorder in elderly
      women in current century. Estrogen has an important role in osteogenesis and
      prevention of bone fractures. Hormone replacement therapy (HRT) is usually
      accompanied by such effects as breast and ovary cancers. Thus, there is an
      increasing demand for replacement with plant phytoestrogens. This study is
      focused on determining the effects of Foeniculum vulgare extract on proliferation
      and osteogenesis progress in human mesenchymal stem cells. MATERIALS AND METHODS:
      Human mesenchymal stem cells were isolated and treated with different amount of
      plant extracts (0.5 to 100 ug/ml). Extract cytotoxicity was measured using MTT
      assay. The alkaline phosphatase enzyme activity was measured to evaluate the
      differentiation progress. RESULTS: RESULTS of MTT assay and alkaline phosphatase
      activity showed that Foeniculum vulgare extract, at range of 5 to 50 ug/ml, may
      positively affect cell proliferation and mineralization. The most proliferation
      and enzyme activity were seen with dose of 5 ug/ml. CONCLUSIONS: Foeniculum
      vulgare has been used in Iranian folk medicine for many years. Our in vitro study
      showed that Foeniculum vulgare extract has osteoprotective effects.

PMID- 25050268
TI  - Histophatologic changes of lung in asthmatic male rats treated with hydro
      alcoholic extract of Plantago major and theophylline.
AB  - OBJECTIVE: Plantago major (P. major) is one of the medicinal crops in the world
      which has therapeutic properties for treatment of respiratory and
      gastrointestinal diseases. Theophylline is commonly used for the treatment of
      respiratory diseases. In this study, we investigated the protective effects of
      hydro-alcoholic extract of P. major on lung in asthmatic male rats. MATERIALS AND
      METHODS: 32 male adult rats were randomly divided into 4 groups: The control
      group (C) received normal saline; Asthma (A) group received a normal diet; Asthma
      group treated with Theophylline (200 mg/kg b.w.) (T); Asthma group which received
      p.major (100 mg/kg b.w.) (P). Asthma was induced by citric acid, 0.1 mg in form
      of spraying. The injection of P.major extract and theophylline was administered
      intraperitoneally for four weeks. At the end of the treatment, all of the rats
      were sacrificed and lungs were taken out, fixed, and stained with H&E, toluidine
      blue, and PAS, then histological studies were followed with light microscope.
      RESULTS: RESULTS showed that, in asthmatic group, the mean number of mast cells
      was significantly increased (p<0.05). Thickness of alveolar epithelium and
      accumulation of glycoprotein in airways was increased. Moreover, in some of
      alveolar sac hemorrhaging was observed. Administration of p.major extract in
      asthmatic rats restored these changes towards normal group. CONCLUSION: The
      present study revealed that P. major compared with theophylline, has a protective
      effect on lung in asthmatic rats.

PMID- 25050269
TI  - Effect of Nigella sativa on the kidney function in rats.
AB  - OBJECTIVES: Nigella sativa (N. sativa) is an amazing herb which is used in
      traditional medicine for a wide range of illnesses including bronchial asthma,
      dysentery, gastrointestinal problems, as well as beneficial effect on blood
      lipids, lowering blood pressure, serum cholesterol, and triglycerides level. This
      study aimed to determine the toxic effect of N. sativa powder on the kidney
      function which was evaluated by serum urea and creatinine and through
      histopathological examination of kidney tissue. METHODS AND MATERIALS: In this
      study, 24 male Sprague Dawley rats were randomly divided into four groups (six
      each). The rats were kept in the separate cage with three rats per cage. The
      treatment groups were given rat pellet containing N. sativa dose at 0.01, 0.10,
      and 1.00 g/kg body weight which were considered as low, normal, and high dose for
      five weeks while control group fed with rat chow pellet without supplementation.
      At the end of 35 days, the rats were sacrificed to take the blood sample and to
      remove the kidney organ for toxicity evaluation. Statistical analyses were done
      through one-way ANOVA using SPSS. RESULTS: The finding revealed that there was no
      significant difference in serum urea of treatment groups compared with the
      control group. The results showed a significant decline in serum creatinine of
      high dose of Nigella sativa treated compared with low dose treated and control
      groups (p<0.05). Histopathological examination of kidney tissue showed normal
      kidney architecture with no tissue degeneration, inflammation, necrosis, and
      tubular dilation in all groups. CONCLUSION: With the evidence of normal urea and
      creatinine level in blood and normal kidney tissue in histology examination for
      all treatment groups, it is suggested that there is no toxic effect on kidney
      function of Nigella sativa at different doses for five-week period.

PMID- 25050270
TI  - Crataegus monogyna fruit aqueous extract as a protective agent against
      doxorubicin-induced reproductive toxicity in male rats.
AB  - OBJECTIVE: Doxorubicin (DOX) is a broad spectrum chemotherapeutic agent used in
      the treatment of several malignancies. The use of DOX in clinical chemotherapy
      has been restricted due to its diverse toxicities, including reproductive
      toxicity. Crataegus monogyna (C. monogyna) is one of the oldest medicinal plants
      that have been shown to be cytoprotective because of scavenging free radicals.
      The present study was undertaken to determine whether C. monogyna fruits aqueous
      extract could serve as a protective agent against reproductive toxicity during
      DOX treatment in a rat model through antioxidant-mediated mechanisms. MATERIALS
      AND METHODS: Male Wistar rats were allocated to four groups. Two groups of rats
      were treated with DOX at a dose of 4 mg/kg intraperitoneally on days 1, 7, 14,
      21, and 28 (accumulated dose of 20 mg/kg). One of the groups received C. monogyna
      fruits aqueous extract at a dose of 20 mg/kg per day orally for 28 days along
      with DOX. A vehicle-treated control group and a C. monogyna control group were
      also included. RESULTS: The DOX-treated group showed significant decreases in the
      body and organ weights and spermatogenic activities as well as many histological
      alterations. DOX treatment also caused a significant decrease in sperm count and
      motility with an increase in dead and abnormal sperms. Moreover, significant
      decrease in serum levels of testosterone and increased serum concentrations of
      FSH, LH, LDH, CPK, and SGOT were observed in DOX-treated rats. Notably, Crataegus
      co-administration caused a partial recovery in above-mentioned parameters.
      CONCLUSION: These findings indicated that doxorubicin can adversely damage the
      testicular tissue, while Crataegus co-administration could effectively prevent
      these adverse effects by effective inhibiting oxidative processes and restoration
      of antioxidant defense system.

PMID- 25050271
TI  - Effects of Carthamus tinctorius L. on the ovarian histomorphology and the female
      reproductive hormones in mice.
AB  - OBJECTIVE: Carthamus tinctorius L. (Safflower) is a member of the asteraceae
      family which had been classified as a fertility regulator in the traditional
      medicine. The purpose of this study was to investigate its possible effects on
      the ovarian histomorphology and the levels of female reproductive hormones in the
      mice. MATERIALS AND METHODS: Sixty adult female Balb/C mice were selected and
      randomly divided into one control and three experimental groups (n= 15). The
      control group received only distilled water, while experimental groups were
      administered intraperitoneally C. tinctorius extract at doses of 0.7, 1.4, and
      2.8 mg/kg/day for 49 consecutive days. In the end of experiments, blood samples
      were collected and the sera were analyzed for the levels of FSH, LH, estrogen,
      and progesterone. Ovarian tissue samples were also taken and histomorphological
      changes of the ovaries were examined using optical microscope. The quantitative
      results were statistically analyzed by one-way ANOVA test. RESULTS: The present
      findings showed that treatment with different concentrations of C. tinctorius
      extract reduced the number of ovarian follicles but number of atretic follicles
      showed an increase. The number and size of the corpora lutea were not affected by
      extract administration. In addition, in the treated mice with C. tinctorius
      extract, the thickness of the tunica albuginea was increased but the relative and
      absolute weights of the ovaries decreased significantly. Furthermore, the blood
      levels of the FSH and estrogen were decreased in the three experimental groups
      compared with those of the control animals. CONCLUSION: The present findings
      indicated that treatment with C. tinctorius extract has detrimental effects on
      the ovarian histomorphology and female reproductive hormones therefore popular
      consumption of this plant should be reconsidered.

PMID- 25050272
TI  - Hypolipidemic and antioxidative effects of curcumin on blood parameters, humoral
      immunity, and jejunum histology in Hy-line hens.
AB  - OBJECTIVE: Turmeric (Curcuma Longa Linn) is a medicinal plant that contains
      curcumin. There is a growing interest in using curcumin powder (CP) as feed
      additives for antioxidative and antimicrobial properties to improve human health.
      This study was conducted to determine the appropriate levels of CP on blood
      parameters, immunity, and histology of jejunum in hens. MATERIALS AND METHODS: A
      total of 200, 58-wk-old Hy-line hens were randomly distributed into 4 treatments
      (0%, 0.5%, 1.5%, and 2.5% CP or 0, 5, 15, and 25 g/kg feed, respectively) with 5
      replicates (10 birds each) for 8 weeks using the completely randomized design.
      Blood samples were taken from 2 birds per replicate at weeks 61 and 65 to
      evaluate blood parameters. On weeks 63 and 65, two birds from each replicate
      received 0.5 ml SRBC (25%) injection in breast muscle and 7 days later, blood
      samples were collected to evaluate total Ig, IgG, and IgM titers in serum. Two
      hens were sacrificed at week 65 for the histological study of jejunum. RESULTS:
      Curcumin reduced triglycerides at 1.5% and 2.5% and cholesterol and LDL at 2.5%
      (p<0.05). Improvement of total Ig and IgG titers after the 1(st) and 2(nd)
      injections were observed. Muscle thickness in jejunum increased (p<0.05) at 1.5%
      curcumin and the length and surface area of villus were enhanced as well.
      CONCLUSION: Our results demonstrate that curcumin can be used as an antioxidant
      at 1.5% and antilipidemic agent at 2.5% in diet.

PMID- 25050273
TI  - Analgesic effect of the aqueous and ethanolic extracts of clove.
AB  - OBJECTIVE: The beneficial effects of clove on toothache have been well
      documented. We have also previously shown the analgesic effects of clove
      essential oil. The present work was done to investigate the analgesic effects of
      the aqueous extract of clove using hot plate test. The possible role of opioid
      receptors in the analgesic effects of clove was also investigated using naloxone.
      MATERIALS AND METHODS: Ninety male mice were divided into nine groups: (1)
      Saline, (2-4) Aaqueous (Aq 50, Aq 100, and Aq 200) groups which were treated with
      50, 100, and 200 mg/kg of aqueous extract of clove, respectively, (5-7) Ethanolic
      (Eth 50, Eth 100, and Eth 200) groups which were treated with 50, 100, and 200
      mg/kg of ethanolic extract of clove, respectively, and (8-9) Aq 100- Naloxone and
      Aq 200- Naloxone which were pretreated with 4 mg/kg of naloxone before injection
      of 100 or 200 mg/kg of the aqueous extract. The hot plate test was performed as a
      base record 10 min before injection of drugs and consequently repeated every 10
      minutes after the injection. RESULTS: The maximal percent effect (MPE) in the
      animal groups treated with 50, 100, and 200 mg/kg of aqueous extract was
      significantly higher than the control group. Pretreatment with naloxone reduced
      the analgesic effects of both 100 and 200 mg/kg of the aqueous extract.
      Administration of all three doses of the ethanloic extract also non-significantly
      increased the MPE. CONCLUSION: The results of the present study showed that
      aqueous extract of clove has analgesic effect in mice demonstrated by hot plate
      test which is reversible by naloxone. The role of opioid system in the analgesic
      effect of clove might be suggested. However, more investigations are needed to
      elucidate the exact mechanism(s).

PMID- 25050274
TI  - Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in
      animal models.
AB  - OBJECTIVE: This study was aimed to examine the antinociceptive and anti
      inflammatory effects of Urtica dioica leaf extract in animal models. MATERIALS
      AND METHODS: Hydroalcoholic extract of the plant leaves was prepared by
      percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g)
      were randomly distributed in control, standard drug, and three experimental
      groups (n=6 in each group). Acetic acid-induced writhing, formalin test, and
      carrageenan-induced paw edema were used to assess the antinociceptive and anti
      inflammatory effects. RESULTS: The extract dose-dependently reduced acetic acid
      induced abdominal twitches. In formalin test, the extract at any of applied doses
      (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase
      while doses of 200 and 400 mg/kg significantly inhibited the second phase of
      formalin test. In carrageenan test, the extract at a dose of 400 mg/kg
      significantly inhibited the paw edema by 26%. CONCLUSION: The results confirm the
      folkloric use of the plant extract in painful and inflammatory conditions.
      Further studies are needed to characterize the active constituents and the
      mechanism of action of the plant extract.

PMID- 25050275
TI  - Simulation of metabolism-based herb-drug interaction: towards safe and
      efficacious use of NIPRD-AM1.
AB  - OBJECTIVE: To evaluate the effect of NIPRD-AM1 on CYP3A4 in order to generate
      clinically significant data for its safe and efficacious use. MATERIALS AND
      METHODS: NIPRD-AM1 is a phytomedicine developed from aqueous root extracts of
      Nauclea latifolia Smith (Rubiaceae) for the treatment of uncomplicated malaria.
      The effect of NIPRD-AM1 on CYP3A4 was measured with and without the addition of
      NIPRD-AM1, by testing different concentrations of the product at 37  degrees C in
      reactive mixtures with ketoconazole (2.5 uM) as the positive control. RESULTS:
      RESULTS showed a very low IC50 value of 0.01 mg/ml similar to that of
      ketoconazole (0.016 mg/ml). CONCLUSION: Metabolic processes of NIPRD-AM1 are
      likely to inhibit CYP3A4, with potential implication on drugs that are CYP3A4
      substrates. This is a promising approach for guidance towards the safe and
      efficacious use of NIPRD-AM1.

PMID- 25050276
TI  - Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a
      review.
AB  - OBJECTIVE: In this study, the current literatures on the use of herbs and herbal
      preparations of Traditional Chinese and Indian Medicine for the treatment of
      opioid addiction were reviewed. Matherials and Methods: Search was done in
      databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google
      Scholar. RESULTS: Among 18 retrieved studies, 3 studies were about asafetida
      extract, an approved preparation for ameliorating drug abstinence in China.
      Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a
      water extract of dai-bofu-to) as well as Indian ones, Mentate and Shilajit, were
      reported to have positive effects against opioid withdrawal, dependence, and
      tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to
      extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia
      Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning
      capsule, and Xuan Xia Qudu Jiaonang (WeiniCom) from Chinese preparations, showed
      anti-addiction effects in randomized, double-blind and, in some studies,
      multicenter clinical trials. Conclusion : Traditional herbal preparations of
      China and India have anti-addiction effects with less adverse effects than alpha2
      adrenergic or opioid agonists.

PMID- 25050277
TI  - Evaluation of cardioprotective effect of silk cocoon (Abresham) on isoprenaline
      induced myocardial infarction in rats.
AB  - OBJECTIVE: The study was conducted to evaluate cardioprotective effect of silk
      cocoon (Abresham) Bombyx mori (B. mori) on isoprenaline-induced myocardial
      infarction. This study deals with the cocoons, which is called Abresham in the
      Unani system of medicine. It is one of the 64 drugs which Avicenna has mentioned
      in Avicenna's tract on cardiac drugs and used in the treatment of cardiovascular
      diseases. Abresham is a chief ingredient of the two very famous Unani formulation
      viz. Khamira Abresham Sada, and Khamira Abresham Hakim Arshad Wala. MATERIALS AND
      METHODS: The ethanolic extract of B. mori (Abresham) silk cocoons in the dose of
      250 mg/kg and 500 mg/kg body weight was administered orally for 28 days before
      isoprenaline administration to test their cardioprotective effect. Isoprenaline
      (85 mg/kg) was administered subcutaneously on days 29(th) and 30(th),
      respectively in order to induce myocardial infarction. RESULTS: The parameters
      for evaluation of cardioprotective activity were the physical parameters and the
      biochemical estimations. The physical parameters were gross examination of heart,
      heart weight/body weight ratio and histopathology examination. In biochemical
      estimations, the activity of various cardiac enzymes such as aspartate
      transaminase, alanine transaminase, creatinine kinase, lactate dehydrogenase, and
      the gold marker troponin-I were determined. The levels altered by isoproterenol
      were restored significantly by the administration of the both doses of test
      extract especially at higher dose. CONCLUSION: The result of this study shows
      that alcoholic extract B. mori has significant cardioprotective activity against
      isoprenaline-induced myocardial infarction.

PMID- 25050278
TI  - Immunomodulatory activity of geranial, geranial acetate, gingerol, and eugenol
      essential oils: evidence for humoral and cell-mediated responses.
AB  - OBJECTIVE: The immunomodulatory effect of geranial, geranial acetate, gingerol,
      and eugenol essential oils were evaluated by studying humoral and cell-mediated
      immune responses. MATERIALS AND METHOD: The essential oils were evaluated for
      immunomodulatory activity in in vivo studies, using rats as the animal model. The
      essential oils were tested for hypersensitivity and hemagglutination reactions,
      using sheep red blood cells (SRBC) as the antigen while sodium carboxy methyl
      cellulose (SCMC) served as the control in all the tests. RESULT: Orally
      administrated essential oils showed a significant increase of test parameters,
      viz., haemagglutinating antibody titre (HAT) and delayed type hypersensitivity
      (DTH) response. In rats immunized with sheep RBC, essential oils enhanced the
      humoral antibody response to the antigen and significantly potentiated the
      cellular immunity by facilitating the foot pad thickness response to sheep RBC in
      sensitized rats with doses of 50-800 mg/ml. Haemagglutination titre of geraniol
      showed the highest increase of 139.3+/-6.38 and with 5.9+/-0.7 DTH, respectively.
      For geranial acetate, the haemagglutination titre showed a moderate increase of
      87.5+/-5.9 and highest increase in DTH with 5.9+/-0.8, respectively. Using
      gingerol, the haemagglutination titre showed a moderate increase with 88.2+/
      6.306 and DTH 3.5+/-0.5, respectively and for eugenol, the haemaggulation titre
      showed a moderate increase with 112.06+/-6.169 and DTH 4.4+/-0.6, respectively.
      These differences were statistically significant. CONCLUSION: The essential oils
      were found to have a significant immunostimulant activity on both the specific
      and non-specific immune mechanisms.

PMID- 25050279
TI  - Turmeric active substance, curcumin, enhanced apomorphine-induced yawning in
      rats.
AB  - OBJECTIVE: Curcumin is a major constituent of turmeric and influences many
      functions of the brain. In the present study, we investigated the effect of
      curcumin on yawning induced by apomorphine in rats. MATERIALS AND METHODS:
      Curcumin administered orally for 10 consecutive days. Yawning was induced by
      subcutaneous (s.c.) injection of apomorphine (a dopamine receptor agonist) and
      the number of yawns was recorded for a period of 30 min. RESULTS: Apomorphine
      (0.05 and 0.1 mg/kg) produced yawning. Haloperidol (a dopamine receptors
      antagonist) at a dose of 0.05 mg/kg partially and at a dose of 0.2 mg/kg
      completely inhibited apomorphine-induced yawning. Curcumin alone produced no
      yawning, whereas at doses of 30 and 60 mg/kg, it increased yawning induced by 0.1
      mg/kg of apomorphine. Curcumin at the high doses (30 and 60 mg/kg) produced
      yawning when apomorphine (0.1 mg/kg) action was partially blocked with 0.5 mg/kg
      of haloperidol. In the presence of complete blockade of apomorphine (0.1 mg/kg)
      action with 0.2 mg/kg of haloperidol, curcumin did not produce yawning.
      CONCLUSION: The results showed that curcumin at high doses increased apomorphine
      induced yawning. In the presence of partial, but not complete blockade of
      apomorphine action, curcumin produced yawning. Curcumin produced a dopamine-like
      effect on yawning.

PMID- 25050280
TI  - Application of Zataria multiflora Boiss. and Cinnamon zeylanicum essential oils
      as two natural preservatives in cake.
AB  - OBJECTIVE: Oxidation of oils has an important effect on nutritional and
      organoleptic properties of foodstuffs. Nowadays, new tendency has created a
      necessity to use natural compounds such as essential oils for producing
      functional foods. In this study, antioxidant, antifungal, and organoleptic
      properties of Zataria multiflora Boiss. (ZMEO) and Cinnamon zeylanicum essential
      oils (CZEO) have been checked as two natural preservatives in the cakes.
      MATERIALS AND METHODS: The antioxidant activity of essential oils were determined
      by measuring thiobarbituric, peroxide, and free fatty acid values of prepared
      cakes during 60 days storage at 25 C. Antifungal properties of essential oils
      were determined and given as the ratio of colony number in samples containing
      ZMEO and CZEO to the control. RESULTS: Different concentrations of essential oils
      prevented oxidation rate and reducd preliminary and secondary oxidation products
      compared with butylate hydroxyanisole (BHA (100 and 200 ppm)) and control cakes.
      Moreover, ZMEO and CZEO at three concentrations (500, 1000, and 1500 ppm) reduced
      the fungal growth more than samples containing BHA (100 and 200 ppm) and the
      control. CONCLUSION: Our results showed that optimum concenteration of ZMEO and
      CZEO for using in the cakes was 500 ppm therefore it can be replaced instead of
      synthetic preservatives in foodstuffs.

PMID- 25050281
TI  - Effect of aqueous fraction of Rosa damascena on ileum contractile response of
      guinea pigs.
AB  - OBJECTIVE: The use of drugs with herbal origin is increasing for treatment of
      gastrointestinal (GI) disorders. Rosa damascena (R. damascena) is a well-known
      plant suggested to have beneficial effect on GI system. In this study, the effect
      of aqueous fraction of R. damascena on the contractions of isolated guinea pig
      ileum was investigated. MATERIALS AND METHODS: Aqueous fraction of plant was
      obtained from ethanolic extract after ethyl acetate and n-butanol fractions were
      discarded. To evaluate effect of this fraction on ileum contraction, guinea pig
      ileum was removed and mounted on organ bath and its contraction was recorded.
      Effect of various concentrations (0.66, 0.83, and 1.3 mg/ml) of aqueous fraction
      on ileum contraction in comparison with Ach in presence and absence of atropine,
      a muscarinic antagonist of cholinergic, was evaluated. The response of ileum to 1
      ug/ml of acetylcholine was considered as 100% response. RESULTS: Our results
      showed that aqueous fractions of R. damascena dose-dependently increased basal
      guinea pigs ileum contractions (p<0.05 to p<0.001). Maximal contraction of
      fraction (1.3 mg/ml) induced 23.4 % of maximal Ach response. The contraction of
      ileum to aqueous fraction was significant decreased in presence 0.001 ug/ml of
      atropine. CONCLUSION: It is concluded that aqueous fraction of R. damascena has
      mild excitatory effect on ileum contraction and this fraction may be beneficial
      as a mild laxative agent.

PMID- 25050282
TI  - Ethnobotanical investigation of traditional medicinal plants commercialized in
      the markets of Mashhad, Iran.
AB  - OBJECTIVE: An ethnobotanical survey on the medicinal plant species marketed in
      Mashhad city, northeastern Iran, was conducted in order to document traditional
      medicinal knowledge and application of medicinal plants. MATERIALS AND METHODS:
      This study was undertaken between 2011 and 2012. The indigenous knowledge of
      traditional healers used for medicinal purposes were collected through
      questionnaire and personal interviews during field trips. Ethnobotanical data was
      arranged alphabetically by family name followed by botanical name, vernacular
      name, part used, folk use, and recipe. Correct identification was made with the
      help of the various Floras and different herbal literature at the Ferdowsi
      University of Mashhad Herbarium (FUMH). RESULTS: The present investigation
      reported medicinal information for about 269 species, belonging to 87 vascular
      plant families and one fungus family. The most important family was Lamiaceae
      with 26 species, followed by Asteraceae with 23, Fabaceae with 20, and Apiaceae
      with 19. Herbal medicine uses reported by herbalists was classified into 132
      different uses which show significant results to treat a wide spectrum of human
      ailments. Plants sold at the market were mostly used for digestive system
      disorders, respiratory problems, urological troubles, nervous system disorders,
      skin problems, and gynecological ailments. CONCLUSION: This survey showed that
      although people in study area have access to modern medical facilities, a lot of
      them still continue to depend on medicinal plants for the treatment of healthcare
      problems. The present paper represents significant ethnobotanical information on
      medical plants which provides baseline data for future pharmacological and
      phytochemical studies.

PMID- 25050283
TI  - Histological, ultrastructural and biochemical studies on the kidney of mice
      treated with Carthamus tinctorius L. extract.
AB  - OBJECTIVE: Carthamus tinctorius L. (C. tinctorius) is used as a food additive but
      also has medicinal applications. The present work was designed to investigate its
      probable side effects on the histology and function of the kidney in the mice.
      MATERIALS AND METHODS: Sixty adult Balb/C mice were randomly distributed into one
      control and three experimental groups. The control group received only distilled
      water, while experimental groups were administered intraperitoneally C.
      tinctorius at doses of 0.7, 1.4, and 2.8 mg/kg for 49 consecutive days. In the
      end of experiments after blood sampling, the biochemical analyses of plasma were
      performed. Tissue samples were also taken and structural alterations were
      examined using light and electron microscopes. RESULTS: There were histological
      changes included decreasing in the diameter of glomerules, increase of proximal
      tubular lumen, tubular necrosis, leuckocyte infiltration, and massive congestion
      in the kidney of the 1.4 and 2.8 mg/kg C. tinctorius groups. Moreover,
      ultrastructural study revealed destruction of the glomerular basement membrane,
      shrinkage of podocyte?s nucleus, and reduction in the number and size of
      microvilli in epithelial cells of renal tubules. Furthermore, the levels of
      creatinine in the plasma of 1.4 and 2.8 mg/kg C. tinctorius groups showed a
      significant increase in comparison with the control group (p<0.05). CONCLUSION:
      It is concluded that C. tinctorius extract exposure at doses of 1.4 and 2.8 mg/kg
      has harmful effects on the renal tissue and therefore, popular consumption of
      this plant should be reconsidered.

PMID- 25050284
TI  - Preventive effects of hydroalcoholic extract of saffron on hematological
      parameters of experimental asthmatic rats.
AB  - OBJECTIVE: Asthma is a chronic inflammatory disease of the respiratory airways
      distinguished by edema and infiltration of inflammatory immune cells. To test our
      hypothesis about the anti-inflammatory effect of saffron, we examined effects of
      Crocus sativus (C. sativus) extract as a prophylactic anti-inflammatory agent in
      sensitized rats. MATERIALS AND METHODS: To induce experimental asthma, rats were
      sensitized with injection and inhalation of ovalbumin (OA). Forty male Wistar
      rats were divided into 5 groups (n=8 for each): control, sensitized (asthma), and
      sensitized and pretreated with three different concentrations of extract, 50,
      100, and 200 mg/kg, 2 times a week (group asthma+50EX, group asthma+100EX, and
      group asthma+200EX). After 32 days, total white blood cells (WBC) counts, red
      blood cells (RBC), and platelet counts in blood were examined. RESULTS: Total WBC
      number and eosinophil and neutrophil percentage in blood were increased, but
      lymphocyte decreased in sensitized animals compared with those of control group
      (p<0.05 to p<0.001). We observed also elevated levels in RBC and platelet counts
      after sensitization in the asthma group. Pretreatment of sensitized rats in all
      concentrations decreased WBC count which was significant in first two
      concentrations (p<0.01 compared with group asthma). All concentrations of extract
      decreased eosinophil percentage significantly (p<0.001 compared with group
      asthma), however, for neutrophil percentage this improvement was not significant.
      Lymphocyte percentage increased in group asthma+100EX compared with group asthma
      (p<0.05). Moreover, in all concentrations, the extract reduced RBC and platelet
      count in pretreated sensitized rats compared with group asthma (p<0.01 to
      p<0.001). CONCLUSION: Our findings indicated that the extract of C. sativus could
      be useful to prevent asthma as an anti-inflammatory treatment.

PMID- 25050285
TI  - Peganum harmala intoxication, a case report.
AB  - OBJECTIVE: Peganum harmala (P. harmala), "Espand" in Persian, has small seeds and
      has been used in traditional medicine as emmenagogue and an abortifacient. It has
      various pharmacological effects such as antifungal, antibacterial, hypothermic,
      anticancer, antinociceptive, and reversible monoamine oxidase inhibition. CASE
      DETAILS: This case was a 45 years old woman who ingested about 50 grams seed of
      P. harmala for hypermenorrhae. She suffered nausea, vomiting, dizziness, tremor,
      ataxia, and confusion. On physical examination, she had hypotension (BP=90/60
      mmHg) with normal heart rate (60 beat/min) and impaired knee to heel test. Her
      consciousness was reduced without any hallucination. Her laboratory test was
      normal. She was discharged at good condition 18 hours later. CONCLUSION: In
      conclusion, physicians working in Iran and other regions that P. harmala is
      prescribed or used illegally, should know signs and symptoms of its toxicity in
      order to be able to deal with the emergencies, however, prognosis of these
      toxicity is not bad.

PMID- 25050286
TI  - The effects of Artemisia aucheri extract on hepatotoxicity induced by
      thioacetamide in male rats.
AB  - OBJECTIVE: Liver is an important organ that is exposed to many oxidant and
      carcinogenic agents, thus antioxidant compounds are beneficial for liver health.
      Artemisia contains flavonoid compounds and anti-diabetic, antioxidant, and anti
      inflammatory properties. Due to possessing terpene and sesquiterpene compounds,
      this plant has antioxidant properties. This study was done to investigate the
      effects of Artemisia plant extract on thioacetamide-induced hepatotoxicity in
      Wistar rats. MATERIALS AND METHODS: For induction of hepatotoxicity, 50 mg/kg
      thioacetamide was injected intraperitoneally (i.p). After extraction and
      purification, the hydroalcoholic extract was injected i.p. at 100, 200, and 300
      mg/kg doses for 21 days together with thioacetamide at 50 mg/kg dose in the last
      3 days. After blood sampling and separation of serum, alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and
      total protein concentrations were measured. RESULTS: Significant decreases in
      aminotransferase and alkaline phosphatase activities and significant increases in
      the concentration of albumin and total protein in groups treated with the extract
      compared with thioacetamide-treated group were observed (p<0.05). CONCLUSION: The
      results indicate that protective effects of Artemisia extract against the
      thioacetamide-induced hepatotoxicity may be due to its ability to block the
      bioactivation of thioacetamide, primarily by inhibiting the activity of Cyp450
      and free radicals. Artemisia possesses quercetin. Studies have demonstrated that
      quercetin inhibits lipid peroxidation and as an antioxidant can inhibit lipid
      peroxidation.

PMID- 25050287
TI  - Analgesic, neuropharmacological, anti-diarrheal, and cytotoxic activities of the
      extract of Solanum sisymbriifolium (Lam.) leaves.
AB  - OBJECTIVE: The present study was undertaken to evaluate the possible analgesic,
      neuropharmacological, anti-diarrheal, and cytotoxic activities of the ethanol
      extract of leaves of Solanum sisymbriifolium Lam. (Family: Solanaceae). MATERIALS
      AND METHODS: The analgesic activity was measured by acetic acid-induced writhing
      inhibition test. The neuropharmacological activities were evaluated using hole
      cross, hole board, and elevated plus-maze test and the anti-diarrheal activity
      was assessed using castor oil-induced diarrhea inhibition method. Brine shrimp
      lethality bioassay was carried out for assessing the cytotoxicity of the ethanol
      extract of the leaves. Except cytotoxic activity, all the tests were conducted on
      mice. RESULTS: The extract at oral doses of 200 and 400 mg/kg body weight showed
      highly significant (p<0.001) decrease in number of writhing, 52.1+/-0.66 and
      4.4+/-0.64 compared with the control (78.6+/-0.29) with the percentage of
      inhibitions of writhing response were found to be 33.72% and 94.40%,
      respectively. Compare with the control, the extract at both doses showed
      significant sedative effect in hole cross test. In hole board test, the extract
      exhibited highly significant (p<0.001) anxiolytic activity at dose of (200
      mg/kg), while the same activity was observed at dose of 400 mg/kg in elevated
      plus-maze test. The extract showed highly significant (p<0.001) anti-diarrheal
      activity in a dose-dependent manner. With the extract, significant lethality to
      brine shrimp was found with LC50 value of 61.66+/-0.9 MUg/ml, which was
      comparable with the positive control (LC50: 11.89+/-0.8 ug/ml). CONCLUSION: The
      results from the present studies support the traditional uses of this plant part
      and could form the basis of further investigation including compound isolation.

PMID- 25050288
TI  - Characterization of phytoconstituents and evaluation of total phenolic content,
      anthelmintic, and antimicrobial activities of Solanum violaceum Ortega.
AB  - OBJECTIVE: The present study was conducted to detect possible chemicals
      (phytoconstituents), prove ethno-medicinal value of the plant, and investigate
      antimicrobial, anthelmintic, and total phenolic content of crude methanolic
      extract of the Solanum violaceum plant. MATERIALS AND METHODS: Phytochemical
      screening was carried out using different chemical group test methods. In
      anthelmintic activity test (using Pheretima posthuma model), five concentrations
      (10, 20, 30, 40, 50, and 80 mg/ml in distilled water) of extracts and albendazole
      as standard were used which involved the vermifuge and vermicidal activity on the
      worms. For the evaluation of in vitro antimicrobial activity, disc diffusion
      method, and to determine the total phenolic content, Folin-Ceocalteu method
      (gallic acid as standard) were used. RESULTS: The phytoconstituent analysis
      revealed presence of alkaloids, carbohydrate, glycoside, flavonoid, saponin, gum,
      diterpenes, phenol, protein, and tannin. The crude extract exhibited significant
      anthelmintic property comparing with the standard. The methanolic extract
      revealed broad-spectrum antimicrobial activity at the concentration of 400
      ug/disc. The results were compared with that of the standard ciprofloxacin. The
      extract exhibited moderate amount of total phenolic compound (54.67+/-1.18 mg/gm
      of gallic acid equivalent). CONCLUSION: Since S. violaceum have shown
      antimicrobial, antioxidant, and anthelmintic activities, more studies such as
      anti-inflammatory, analgesic, antipyretic, and other pharmacological activities
      should be carried out to justify its traditional use, as the plant is available
      and used broadly in the rural areas for folkloric remedies.

PMID- 25050289
TI  - Effects of combinations of curcumin, linalool, rutin, safranal, and thymoquinone
      on glucose/serum deprivation-induced cell death.
AB  - OBJECTIVE: Several phytochemical agents have been known to exhibit a
      neuroprotective effect. Among them, curcumin, linalool, rutin, safranal, and
      thymoquinone were widely investigated and neuroprotective activity of each of
      them was shown by several studies. This work was planned to investigate whether
      different combinations of them could induce better neuroprotective effect against
      glucose/serum deprivation (GSD)-induced cytotoxicity. MATERIALS AND METHODS: PC12
      cells were cultivated for 8 h in GSD condition in both the absence and presence
      of curcumin, linalool, rutin, safranal, thymoquinone, or combinations of them. At
      the end of the experiment, the cell viability was determined using MTT assay.
      RESULTS: The cells cultured in GSD condition showed a significant decrease in
      viability (28+/-1%) as compared with those cultured in standard condition (100+/
      2%). In the presence of curcumin (10 ug/ml), linalool (16 ug/ml), rutin (200
      ug/ml), safranal (50 ug/ml), and thymoquinone (1 ug/ml), the cell viability
      increased to 69+/-3.4% (p<0.001), 44+/-1.4% (p<0.01), 64+/-0.5% (p<0.001), 49+/
      2% (p<0.001), and 70+/-3.2% (p<0.001), respectively. When different combinations
      of the agents were tested, the best cytoprotective activity was obtained from
      safranal + curcumin + thymoquinone (97+/-5%, p<0.01 vs. untreated cells).
      CONCLUSIONS: The present study demonstrated that a combination of safranal +
      curcumin + thymoquinone can block GSD-induced cell death and has the potential to
      be considered for management of cerebral ischemia and neurodegenerative diseases.

PMID- 25050290
TI  - The effects of gallic acid on pain and memory following transient global
      ischemia/reperfusion in Wistar rats.
AB  - OBJECTIVE: It is generally agreed that most of the phenomena observed during
      brain ischemia and reperfusion can be explained by the damage to membrane
      structure. Oxidative stress is resulted in an imbalance between high consumption
      of oxygen and low levels of endogenous antioxidants. It is known that gallic acid
      (GA) is a strong antioxidant. The present study was carried out to evaluate the
      effect of GA on ischemia/reperfusion (I/R)-induced brain injury in rats.
      MATERIALS AND METHODS: Wistar adult male rats weighing 200-250 g were divided
      into six groups as sham operated (Sh), ischemia/reperfusion (I/R) received normal
      saline (I+Veh), I/R groups treated with gallic acid (I+GA, 50, 100, or 200 mg/kg,
      orally, respectively), or with 100 mg /kg phenytoin (I+Phen). The global cerebral
      I/R injury was induced by occluding bilateral common carotid arteries (BCCA) for
      20 min, followed by 5 days reperfusion in adult male rats. RESULTS: It was found
      that administration of 100 mg/kg GA for 5 days before and 5 days after I/R
      induction reversed gait performance, sensorimotor disorders (p<0.01), and
      hypoalgesia (p<0.001) while dose of 50 mg/kg increased passive avoidance memory
      significantly (p<0.05). CONCLUSION: Our findings clearly demonstrate that GA has
      beneficial effects on behavioral impairments after brain injury induced by I/R.
      The results of this study show that GA pretreatment ameliorates cerebral
      ischemia/reperfusion injury and enhances the antioxidant defense against BCCA
      occlusion-induced I/R in rats, so it exhibits cerebroprotective property.

PMID- 25050291
TI  - Maternal feeding with walnuts (Juglans regia) improves learning and memory in
      their adult pups.
AB  - OBJECTIVE: Walnut (Juglans Regia) is a domestic fruit of Iran. Walnut kernel (WK)
      has many beneficial constituents such as unsaturated fatty acids, antioxidants,
      and vitamin E. Scientific studies have shown that fatty acids and vitamin E can
      modulate learning and memory processes. The aim of the present work was to study
      effects of walnut consumption by mothers during pregnancy and lactation on
      learning and memory in adult rat offsprings. MATERIALS AND METHODS: The animals
      were divided into three groups: control (fed with ordinary food, 20 g daily),
      gestation (fed with WK, 6% of food intake during pregnancy), and gestation and
      lactation (fed with WK, 6% of food intake during gestation and lactation). Morris
      water maze test was performed for their adult offsprings. RESULTS: The results
      showed that there was a significant difference in learning and memory of rat
      offsprings between experimental and control groups. CONCLUSION: These data may
      indicate that feeding mothers with WK results in improvement in learning and
      memory of their offsprings.

PMID- 25050292
TI  - Sesame effects on testicular damage in streptozotocin-induced diabetes rats.
AB  - OBJECTIVE(S): Reproductive dysfunction is a consequence of diabetes. Diabetes is
      associated with changes in testicular tissue. Sesame oil contains large amounts
      of polyunsaturated fatty acids and lignin with antioxidant activity, vitamin E,
      and monounsaturated fatty acid (MUFA). The present study investigated the effects
      of sesame on testis histology and male reproductive parameters in streptozotocin
      induced diabetic rats. MATERIALS AND METHODS: Thirty mature male Wistar rats were
      randomly divided into three groups, i.e., control (C), diabetic-control (DC), and
      sesame-treated diabetic rats (SD). Diabetes was induced by a single dose of
      streptozotocin (65 mg/kg; i.p). The animals were treated by a single
      intraperitoneal sesame extract injection (100 mg/kg b.w.) once daily for 6 weeks.
      RESULTS: The biochemical analysis revealed that the diabetes resulted in
      significant (p<0.05) reduction in spermiogenesis, testosterone, LH, and FSH
      levels. Light microscopic analysis showed remarkable (p<0.05) reduction in STD
      (seminiferous tubules diameter), SPI (spermatogenesis index) thickness of the
      epithelium, and significant increase in thickness of the interstitial tissue in
      the diabetic group compared with the control group. Simultaneous administration
      of the sesame could fairly up-regulate testosterone, LH, and FSH of the animals
      in this group. However, some differences were manifested with improved
      histological features as thickness of the epithelium, seminiferous tubules
      diameter, and spermatogenesis index. CONCLUSION: These data demonstrated that
      sesame significantly improved diabetes complication in rat testis. This study
      suggested that sesame might have a protective effect against oxidative stress
      induced impaired testicular functions in diabetic rats.

PMID- 25050293
TI  - Hydroalcoholic extract of Crocus sativus effects on bronchial inflammatory cells
      in ovalbumin sensitized rats.
AB  - OBJECTIVE: Inflammation is one of the major components of asthma. Our aim was to
      evaluate the effects of C. sativus extract on total and differential white blood
      cells (WBC) count in lung lavage fluid (LLF) of ovalbumin-sensitized rats.
      MATERIALS AND METHODS: Forty rats were divided into five groups (n = 8 for each
      group) as control (C), sensitized with injection and inhalation of ovalbumin (OA)
      alone (S), and three groups of sensitized and treated with different doses of C.
      sativus extract (S50EX, S100EX, and S200EX groups). Total and differential WBC
      counts of LLF were evaluated in control, sensitized, and treated sensitized
      groups. RESULTS: Total WBC count, neutrophil, and eosinophil percentage in LLF
      were increased in sensitized animals compared with the control group (p0.001).
      Treatment of sensitized animals with all doses of the extract significantly
      reduced WBC number and the percentage of neutrophil and eosinophil compared with
      the sensitized animals (p0.01-0.001). CONCLUSION: According to these results, the
      extract of C. sativus could be effective on alleviating lung inflammatory cells
      specially eosinophils in lung lavage of sensitized animals which may indicate a
      preventive effect of this plant on lung inflammation in asthma.

PMID- 25050294
TI  - The effect of natural adjuvants (G2, G2F) on lung inflammation of sensitized
      guinea pigs.
AB  - OBJECTIVE: The effects of natural adjuvants were examined on total and
      differential WBC counts in lung lavage of sensitized guinea pigs. MATERIALS AND
      METHODS: In three sensitized groups of guinea pigs including: untreated
      sensitized animals (S), sensitized animals treated with adjuvant G2 (S+G2) and
      G2F (S+G2F) as well as non-sensitized group (C) (n=6 for each group), total and
      differential WBC counts of lung lavage were examined. Sensitization of animals
      was achieved by injection and inhalation of ovalbumin (OA). RESULTS: The results
      showed increased total WBC, eosinophil, neutrophil, and basophil counts, and
      decreased lymphocytes in lung lavage of sensitized animals compared with the
      control group (p<0.01 for all cases). However, neutrophil, lymphocyte,
      eosinophil, and basophil counts in lung lavage were decreased in treated groups
      with either G2 or G2F but total WBC was decreased in lung lavage of treated group
      with only G2. CONCLUSION: These results indicate important preventive effects of
      two natural adjuvants, especially G2, on lung inflammation of sensitized guinea
      pigs.

PMID- 25050295
TI  - Effect of Phaleria macrocarpa on sexual function of rats.
AB  - OBJECTIVES: The purpose of current study was to determine the effect of Phaleria
      macrocarpa (P. macrocarpa) fruits aqueous extract on reproductive performance of
      adult male rats by assessing the serum testosterone level and evaluating their
      libido behavior. METHODS AND MATERIALS: Eighteen male adult Spraque Dawley rats
      were divided into three groups and designated as treatment (240 mg/kg P.
      macrocarpa aqueous extract), negative control (distilled water), and positive
      control (4 mg/kg testosterone) which were supplemented through intragastric
      gavage for seven weeks. On the seventh week of supplementation, each of the male
      rats was introduced to five female rats at five different days to allow mating
      and observed the libido behavior. The mounting latency and mounting frequency
      were recorded for each mating. RESULTS: P. macrocarpa aqueous extract
      significantly increased (p<0.05) the serum testosterone level and mounting
      frequency of male rats. However, there was no significant effect on mounting
      latency. Body weight was significantly lower in rats supplemented with P.
      macrocarpa aqueous extract compared with the control groups (p<0.05). CONCLUSION:
      P. macrocarpa showed potential value as an alternative for improving the sexual
      strength by increasing the level of testosterone and libido behavior. Thus, it is
      suggested that P. macrocarpa can improve the fertility in man.

PMID- 25050297
TI  - Comparison between effects of different doses of Melissa officinalis and
      atorvastatin on the activity of liver enzymes in hypercholesterolemia rats.
AB  - OBJECTIVES: Liver is one of the most sensitive tissues to oxidant damage. Hence,
      the present study was conducted to compare the effects of Melissa officinalis
      (MO) extract and Atorvastatin on the activity of liver enzymes in rats. MATERIALS
      AND METHODS: In this experimental study, 60 male Wistar rats were selected and
      allocated to six groups (n=10). The control group received a normal diet, sham
      group received a fatty diet while other groups received a fatty diet and the
      alcoholic extract of MO, at minimum (25 mg/kg), moderate (50 mg/kg), and maximum
      (75 mg/kg) doses (i.p.). The last group received Atorvastatin (10 mg/kg) through
      gavage with a fatty diet over a 21-day period. At the end of this 21-day period,
      blood samples were drawn and the levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), and alkaline phosphatase (ALP), activity of
      liver enzymes as well as cholesterol in the samples were measured. RESULTS: The
      obtained results showed that the activity of liver enzymes in the treatment
      groups receiving MO extract and the group receiving Atorvastatin decreased
      significantly. MO extract reduced the level of liver enzymes. CONCLUSION:
      Therefore, further studies for obtaining a better understanding of the mechanism
      of effect of MO for treating liver diseases are recommended.

PMID- 25050296
TI  - Garlic: a review of potential therapeutic effects.
AB  - Throughout history, many different cultures have recognized the potential use of
      garlic for prevention and treatment of different diseases. Recent studies support
      the effects of garlic and its extracts in a wide range of applications. These
      studies raised the possibility of revival of garlic therapeutic values in
      different diseases. Different compounds in garlic are thought to reduce the risk
      for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show
      benefit on high blood glucose concentration. However, the exact mechanism of all
      ingredients and their long-term effects are not fully understood. Further studies
      are needed to elucidate the pathophysiological mechanisms of action of garlic as
      well as its efficacy and safety in treatment of various diseases. 

PMID- 25050298
TI  - Fatty acid composition, antioxidant and antibacterial activities of Adonis
      wolgensis L. extract.
AB  - OBJECTIVES: The objective of this study was to analyze the fatty acid content,
      antioxidant, and antibacterial activities of hydro-methanolic extract of Adonis
      wolgensis L. (A. wolgensis L.) growing wild in north of Iran. MATERIALS AND
      METHODS: Oils of A. wolgensis L. was obtained by means of Soxhlet apparatus from
      leaves and stems. Methyl esters were derived from the oily mixtures by trans
      esterification process and were analyzed by GC/FID and GC/MS systems. Phenolic
      compounds extraction was done with aqueous methanol (90%). This extract was
      investigated for antioxidant activity using DPPH radical scavenging and reducing
      power methods and was also tested against a panel of microorganisms. RESULTS:
      Linolenic acid (45.83%) and oleic acid (47.54%) were the most abundant fatty
      acids in leaves and stems, respectively. Hydro-methanolic extract with the high
      amount of total phenolics (9.20 +/-0.011 mg GAE per dry matter) was the potent
      antioxidant in the assays. RESULTS obtained from measurements of MIC for extract,
      indicated that E. coli, S. aureus, and S. enteritidis were the most sensitive
      microorganisms tested, but no activity was observed against Gram-positive
      microorganism (B. subtilis). CONCLUSION: The results obtained from the present
      study indicated that the oil of A. wolgensis leaves and stems contained a high
      source of poly-unsaturated fatty acids (PUFAs). These results also showed that
      hydro-methanolic extract of this plant contained significant antioxidant and
      antibacterial activities.

PMID- 25050299
TI  - Antitumor properties of two traditional aromatic rice genotypes (Kalijira and
      Chinigura).
AB  - OBJECTIVE: Methanol extract of bran and unpolished grain of two traditional
      aromatic rice genotypes viz. Kalijira and Chinigura were assayed for their
      activity on the growth and initiation of crown-gall tumors on potato disks.
      MATERIALS AND METHODS: Three Agrobacterium tumefaciens (A. tumefaciens) strain
      AtSl0105, AtTa0112, and AtAc0114 were used as the tumor forming agent. Collected
      rice was separated to bran and unpolished grain by different milling processes
      and made into fine powder before extracting using methanol. Antitumor assay of
      plant extracts was performed according to standard potato disc bioassay. Disc
      diffusion assay (Kirby-Bauer Method) was used to screen A. tumefaciens
      sensitivity test. RESULTS: The results demonstrated a high correlation between
      the ability of aromatic rice to inhibit the initiation and growth of crown-gall
      tumors on potato disks. Maximum tumor inhibitions were observed against the
      strain AtSl0105 by Kalijira bran (73.91%) and Chinigura bran (69.56%). Both
      unpolished grains showed significant effect (Kalijira 57.43%, Chinigura 55.53%)
      to inhibit the tumor. CONCLUSION: It can be concluded that aromatic rice
      (Kalijira and Chinigura) might be a potential source of antitumor agent that can
      be used for further drug development for tumor treatment.

PMID- 25050300
TI  - Protective effect of royal jelly on the sperm parameters and testosterone level
      and lipid peroxidation in adult mice treated with oxymetholone.
AB  - Objectives : The aim of the present study was to evaluate protective effect of
      royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA)
      production in mice. MATERIALS AND METHODS: Thirty-two adult male NMRI mice
      weighing 30+/-2 g were used. All the animals were divided into 4 groups. CONTROL
      GROUP: received saline 0.1 ml/mouse/day orally for 30 days. Royal jelly group
      (RJ): received royal jelly at dose of 100 mg/kg daily for 30 days orally.
      Oxymetholone group: the received Oxymetholone (OX) at dose of 5 mg/kg daily for
      30 days orally. Royal jelly+Oxymetholone group: received royal jelly at dose of
      100 mg/kg/day orally concomitant with OX administration. Sperm count, sperm
      motility, viability, maturity, and DNA integrity were analyzed. Furthermore,
      serum testosterone and MDA concentrations were determined. RESULTS: In
      Oxymetholone group, sperm count, motility as well as testosterone concentration
      reduced significantly (p<0.05), while significant (p<0.05) increases in immature
      sperm, sperm with DNA damaged, and MDA concentration were announced in
      Oxymetholone group in comparison with control group and Royal jelly+Oxymetholone
      group. RJ caused partially amelioration in all of the above- mentioned parameters
      in Royal Jelly+Oxymetholone group. CONCLUSION: In conclusion, RJ may be used in
      combination with OX to improve OX-induced oxidative stress and male infertility.

PMID- 25050301
TI  - Relaxant effect of Humulus lupulus extracts on isotonic rat's ileum contractions.
AB  - OBJECTIVE: Many biological studies have been done to determine the activity of
      medicinal plants on gastrointestinal function. Since acetylcholine is the major
      transmitter involved in the gastrointestinal motility and there are some
      evidences regarding the cholinergic modulatory effect of hops extract, in the
      present study spasmolytic and antispasmodic action of hops (Humulus lupulus) on
      acetylcholine-induced contraction in isolated rat's ileum was evaluated. MATERIAL
      AND METHODS: In this study, pieces of isolated rat's ileum were mounted in the
      internal chamber of an organ bath which was filled with Tyrode's solution and
      tightly tied to the lever of an isotonic transducer. The contractile responses
      were recorded by using an oscillograph device. In the presence of normal saline
      and different concentrations of hops (0.1, 0.3, and 0.5 mg/ml), the amplitude of
      contractions induced by10(-12) up to 10(-2) M acetylcholine was determined. The
      spasmolytic action of the same extract concentrations was also examined on
      contraction induced by 10(-4) acetylcholine. RESULTS: Our findings indicate that
      hops extract reduces acetylcholine-induced contraction in all concentrations. The
      significant inhibitory effects of 0.1, 0.3, and 0.5 mg/ml hops extract on
      contraction induced by 10(-3) M acetylcholine were 81.9, 77, and 29.3,
      respectively (p<0.05). CONCLUSION: According to our findings, hops extract poses
      a potent spasmolytic and antispasmodic action on acetylcholine-induced
      contraction in isolated rat's ileum which may be mediated by cholinergic systems.

PMID- 25050302
TI  - Neuropharmacological effects of standardized aqueous stem bark extract of Parkia
      biglobossa in Wistar rats.
AB  - OBJECTIVE: Parkia biglobossa stem bark decoction is a popular medicinal plant
      preparation used as calming agent for tensed patients in traditional medicine.
      The aim of this study was to evaluate the effects of aqueous stem bark extract of
      Parkia biglobossa (AEPB) and its active fraction AEPBF3 on anxiety, spontaneous
      alternation behavior, and locomotor activity. The open field apparatus was used
      to evaluate effects of AEPB and AEPBF3 on locomotion. The APBE and the active
      fraction AEPBF3 were standardized using reverse phase high performance liquid
      chromatography to establish finger print to ascertain identity and stability of
      the extracts over time. MATERIALS AND METHODS: The oral median lethal doses
      (LD50) of AEPB and AEPBF3 were evaluated using modified Lorke's method in rats.
      The effect of APBE (50-200 mg/kg p.o.), APBEF3 (25 and 50 mg/kg p.o.), diazepam
      (2.5 mg/kg, i.p.), and 10 ml normal saline/kg on anxiety-like behavior,
      spontaneous alternation behavior, and locomotion activity were evaluated in rats
      on elevated plus maze (EPM), Zero-maze, Y-maze, and open field apparatus,
      respectively. The oral LD50 values of AEPB and AEPBF3 were estimated to be 5000
      mg/kg and 3800 mg/kg body weight in rats, respectively. RESULTS: AEPB and AEPBF3
      significantly (F6, 41=2342, p<0.0001) increased time spent in the open arm of EPM
      and significantly (F6, 41=2323, p<0.0001) increased time spent in open arms of
      the Zero maze. The AEPB and AEPBF3 administration produced significant increase
      (F5, 35=154, p<0.0001) in spontaneous alternation behavior in rats. The AEPB
      extract and its fraction AEPBF3 significantly increased total locomotor activity
      (F6, 41=413, p<0.0001) and rearing (F6, 41=150, p<0.0001) in the open field
      apparatus. CONCLUSION: The results of the present study provided evidence for
      anxiolytic and nootropic effects of the AEPB and AEPBF3, thus providing
      scientific basis for its continuous use in the management of neuropsychiatric
      disorders characterized by apprehension and amnesia.

PMID- 25050303
TI  - Instant effects of peppermint essential oil on the physiological parameters and
      exercise performance.
AB  - OBJECTIVE: Effect of peppermint on exercise performance was previously
      investigated but equivocal findings exist. This study aimed to investigate the
      effects of peppermint ingestion on the physiological parameters and exercise
      performance after 5 min and 1 h. MATERIALS AND METHODS: Thirty healthy male
      university students were randomly divided into experimental (n=15) and control
      (n=15) groups. Maximum isometric grip force, vertical and long jumps, spirometric
      parameters, visual and audio reaction times, blood pressure, heart rate, and
      breath rate were recorded three times: before, five minutes, and one hour after
      single dose oral administration of peppermint essential oil (50 ul). Data were
      analyzed using repeated measures ANOVA. RESULTS: Our results revealed significant
      improvement in all of the variables after oral administration of peppermint
      essential oil. Experimental group compared with control group showed an
      incremental and a significant increase in the grip force (36.1%), standing
      vertical jump (7.0%), and standing long jump (6.4%). Data obtained from the
      experimental group after five minutes exhibited a significant increase in the
      forced vital capacity in first second (FVC1)(35.1%), peak inspiratory flow rate
      (PIF) (66.4%), and peak expiratory flow rate (PEF) (65.1%), whereas after one
      hour, only PIF shown a significant increase as compare with the baseline and
      control group. At both times, visual and audio reaction times were significantly
      decreased. Physiological parameters were also significantly improved after five
      minutes. A considerable enhancement in the grip force, spiromery, and other
      parameters were the important findings of this study. Conclusion : An improvement
      in the spirometric measurements (FVC1, PEF, and PIF) might be due to the
      peppermint effects on the bronchial smooth muscle tonicity with or without
      affecting the lung surfactant. Yet, no scientific evidence exists regarding
      isometric force enhancement in this novel study.

PMID- 25050304
TI  - Otostegia persica (Lamiaceae): A review on its ethnopharmacology, phytochemistry,
      and pharmacology.
AB  - OBJECTIVE: The current study summarizes the updated information concerning the
      ethnopharmacology, Phytochemistry, and pharmacology of Otostegia persica Boiss.
      (Lamiaceae), an endemic medicinal plant in south and southeast of Iran. MATERIALS
      AND METHODS: Information was collected through bibliographic investigation from
      scientific journals, books, theses, reports, and electronic search (databases
      SCOPUS, Google Scholar, Web of Science, and Science Direct). Moreover,
      documentation from unpublished resources and ethnobotanical surveys has been
      used. The present review covers the literature available from 2003 to 2013.
      RESULTS: In traditional systems of medicine, this plant is reputed for treating
      diabetes, arthritis, gastric discomfort, headache, rheumatism, sedative
      activities, regulating blood pressure, and hyperlipidemia. Phytochemical
      screening of active components and mineral element evaluation of this species
      have been reported. Several types of diterpenoids and flavonols including morin,
      kaempferol, and quercetin are identified from the plant. Most of the
      pharmacological activity of this plant resides in its flavonoid fraction which
      causes antimicrobial and antioxidant activities. Various pharmacological studies
      on O. persica show antimicrobial, antioxidant, anti-inflammatory, anti-diabetic,
      anti-aphid, and hepatoprotective activities. CONCLUSION: Being an endemic plant
      of Iran, this species is an important medicinal herb which can be used for
      various purposes. This review might be helpful for scientists and researchers to
      find new chemical entities responsible for its claimed traditional uses and
      discover new lead compounds for diseases mentioned.

PMID- 25050305
TI  - Identification of phenolic antioxidants in Ipomoea mauritiana jacq. using
      spectrophotometric and mass spectroscopic studies.
AB  - OBJECTIVE: Ipomoea mauritiana is used in both Ayurveda and folk medicine systems.
      The tuberous roots are known to be diuretic, depurative, carminative, and
      anthelmintic. The objective of the current study was to identify phenolic
      antioxidants from I . mauritiana using spectrophotometric and LC-MS analysis.
      MATERIALS AND METHODS: An activity-guided fractionation and purification process
      was used to identify the antioxidative components from I . mauritiana tuber.
      Dried mature tubers of I. mauritiana were extracted with 80% methanol and then
      partitioned by chloroform, ethyl acetate, acetone, and methanol. The acetone
      fraction showed the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging activity among four fractions and was subjected to separation and
      purification using preparative reverse-phase high-performance liquid
      chromatography (HPLC). RESULTS: Two compounds were separated from the acetone
      fraction using preparative LC fraction collector. The purified compounds were
      screened for their antioxidative potential using DPPH assay. The compounds were
      subjected to LC-MS analysis in ESI negative mode. One of the compounds was
      identified as Caffeoyl glucose based on the mass fragmentation. CONCLUSION: The
      acetone fraction showed highest radical scavenging activity and the
      phytoconstituents of the same were identified by LC-MS/MS analysis.

PMID- 25050306
TI  - Investigation of total phenolic content and antioxidant activities of Azadirachta
      indica roots.
AB  - OBJECTIVE: The present study was an attempt to study total phenolic content and
      antioxidant property of the crude ethanolic extract of the roots of Azadirachta
      indica (A. indica). MATERIALS AND METHODS: To evaluate the antioxidant properties
      of the crude extract, some complementary test systems, namely DPPH free radical
      scavenging assay, reducing power assay, and ferrous ion chelating ability and
      determination of total phenolic content were conducted. RESULTS: In DPPH free
      radical scavenging test, IC50 value of the crude extract was found to be fairly
      significant (13.81+/-0.06 MUg/ml) while compared with that of the reference
      standards, ascorbic acid and BHA (2.12+/-0.02 and 4.87+/-0.05 MUg/ml,
      respectively). In reducing power assay, the maximum absorbance for the extract
      was found to be 1.523+/-0.026 at100 MUg/ml compared with standard ascorbic acid
      and BHA (2.811+/-0.013 MUg/ml and 2.031+/-0.019 MUg/ml, respectively). The IC50
      value of the extract as percentage of Fe(++) ion chelating ability was determined
      as 19.01+/-0.024 MUg/ml where EDTA showed 8.87+/-0.035 MUg/ml. The total phenolic
      amount was also calculated quite high in the extract (238.81+/-0.98 mg/g of
      gallic acid equivalent). CONCLUSION: The assays showed the presence of
      significant antioxidant properties of the crude sample, which would justify its
      traditional use. However, it would be very interesting to investigate the
      possible causes and their mechanisms responsible for the antioxidant property of
      the plant A. indica.

PMID- 25050307
TI  - Effects of saffron (Crocus sativus) petal ethanolic extract on hematology,
      antibody response, and spleen histology in rats.
AB  - OBJECTIVE: Saffron petal is a by-product that contains flavonoids and
      anthocyanins. In order to study the effects of saffron petal extract (SPE) on
      blood parameters, immune system, and spleen histology, five treatments (n=6) were
      used in a completely randomized design. MATERIALS AND METHODS: The treatments
      were 0, 75, 150, 225, and 450 mg/kg body weight of SPE. The SPE was injected
      intraperitoneally to 30 rats (10-week old, weighing 225+/-15 g) for 14 days.
      Immunization was performed using 1*10(8) sheep red blood cells (SRBC) on days 0
      and 7 subcutaneously in all treatment groups. On day 15, blood was collected from
      the heart of rats after anesthesia. One part of samples were poured in
      heparinized tubes for counting whole blood cells (CBC) and different white blood
      cells (WBC) and the other part was used to measure IgG using ELISA technique. The
      spleen was stained by hematoxylin- eosin for histological study. The data were
      statistically analyzed using ANOVA program and the means evaluation was done
      using Tukey's test. RESULTS are presented as mean+/-SD. RESULTS: RESULTS showed
      no significant difference between treatments and control group regarding the
      amount of RBC, HGB, HCT, and PLT. The level of IgG at 75 mg/kg was significantly
      increased in comparison with other groups. No changes were observed in spleen
      histology. CONCLUSION: The results indicate that use of SPE at dose of 75 mg/kg
      causes an increase in antibody response without any change in hematological
      parameters and spleen histology.

PMID- 25050308
TI  - Effect of the aqueous extract of Foeniculum vulgare (fennel) on the kidney in
      experimental PCOS female rats.
AB  - OBJECTIVE: Foeniculum vulgare seed (F. vulgare) is an herbal plant which is used
      with phytoestrogene compounds for polycystic ovary syndrome (PCOS) treatment. In
      this research, renoprotective effect of the aqueous extract of Foeniculum vulgare
      (AEF) in experimental PCOS female rats is studied. MATERIALS AND METHODS: Forty
      female rats were randomly divided into five groups. The first group served as
      control, was injected with an equivalent volume (0.2 ml) of normal saline, and
      received normal diet. Animals in the second group were non poly cystic ovary
      syndrome (PCOS) rats which were treated with intragastric administration of
      aqueous extract of F. vulgare (150 mg/kg b.w.). In the third group, the rats were
      treated with intraperitoneal injection of estradiolvalerate (EV) (4 mg in 0.2 ml
      of sesame oil). The fourth groups were treated with EV and AEF (150mg/kg bw) with
      the same route. The fifth groups were treated with EV and AEF (100mg/kg bw).
      After 4 weeks of study, all of the rats were sacrificed, their kidneys tissues
      were processed for light microscopy, and some biochemical parameters of serum
      were measured. RESULTS: The mean values of blood urea nitrogen in PCOS rats
      treated with low dose of AEF and EV and non-treated, was significantly (p<0.05)
      increased compared with non-PCOS and PCOS rats treated with high dose of AEF.
      Moreover, histopathological changes of kidney samples were comparable in PCOS
      rats with respect to treated groups with AEF. CONCLUSION: Aqueous extract of
      fennel seed showed the beneficial effect (especially at dose of 150 mg/kg b.w.)
      on renal function in PCOS rats.

PMID- 25050309
TI  - Effect of Bunium persicum aqueous extract plus endurance exercise on
      cardiorespiratory capacity and serum lipid profile.
AB  - OBJECTIVE(S): We examined the effects of endurance exercise in the presence of
      Bunium persicum extract administration on lipid profile and cardiorespiratory
      capacity in hypercholesterolemic male mice. Materials and Methods : Forty male
      hypercholesterolemic mice were divided into four groups: Vehicle, Endurance
      exercise (EE), Bunium persicum extract (BPE), and EE + BPE. The exercise protocol
      was performed at a speed of 18 m/min, 40 min/day, and 5 days/week for 6 weeks.
      The BPE was administered orally by a dose of 20 mg/Kg/day. RESULTS: The results
      indicated that the 6-week endurance training accompanied by Bunium Persicum
      extract administration increased cardiorespiratory capacity significantly (601+/
      39 vs. 293+/-20 meters, p<0.001). Total cholesterol level was significantly
      reduced in EE + BPE compared with Vehicle and EE groups (p<0.05). LDL-c was lower
      in EE + BPE compared with the Vehicle (p<0.01). HDL-c in BPE and EE + BPE groups
      was significantly higher than Vehicle (p<0.001 and p<0.05, respectively). Serum
      triglyceride level was significantly (p<0.05) lower in BPE than the other three
      groups. Body weight changes were not significantly different between groups.
      CONCLUSION: The results suggested that Bunium persicum extract is very useful in
      improvement of lipid profile in hypercholesterolemic animals. Supplementation of
      the extract to exercise significantly increased the cardiorespiratory capacity.

PMID- 25050310
TI  - Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced
      acute colitis in rats.
AB  - OBJECTIVE: Anti-inflammatory, immuno-modulatory, and antioxidant properties of
      Moringa oleifera Lam. suggest that it might have beneficial effects on colitis.
      The present study was performed to investigate the anticolitis effect of Moringa
      oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF)
      on acetic acid-induced colitis in rats. MATERIALS AND METHODS: Both MSHE and MCF
      with three increasing doses (50, 100, and 200 mg/kg) were administered orally to
      separate groups of male Wistar rats, 2 h before ulcer induction (using acetic
      acid 4%) and continued for 5 days. Prednisolone (4 mg/kg) and normal saline (1
      ml/kg) were used in reference and control groups, respectively. All rats were
      sacrificed 24 h after the last dose (at day 6) and tissue injuries were assessed
      macroscopically and pathologically. RESULTS: Extracts with three doses mentioned
      before were effective to reduce weight of distal colon (8 cm) as a marker for
      inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF
      (100 and 200 mg/kg) were effective to reduce ulcer severity, area, and index as
      well as mucosal inflammation severity and extent, crypt damage, invasion
      involvement, total colitis index, and MPO activity compared with controls. MCF
      (50 mg/kg) was not significantly effective in reducing evaluated parameters of
      colitis compared with controls. CONCLUSION: It is concluded that MSHE and MCF
      were both effective to treat experimental colitis and this might be attributed to
      their similar major components, biophenols and flavonoids. Since the efficacy was
      evident even in low doses of MSHE, presence of active constituents with high
      potency in seeds is persuasive.

PMID- 25050311
TI  - The effects of aqueous extract of Aloe vera leaves on the gastric acid secretion
      and brain and intestinal water content following acetic acid- induced gastric
      ulcer in male rats.
AB  - OBJECTIVE: Gut-brain axis (GBA) is very important in creation and modulation of
      gastrointestinal problems. Aloe vera gel has gastroprotective properties. The
      purpose of this study was to evaluate the effect of aqueous extract of Aloe vera
      leaves on the gastric acid secretion and brain and intestinal water content
      following acetic acid gastric ulcer induction. MATERIALS AND METHODS: Gastric
      ulcer was induced by injection of 20% acetic acid into the subserosal layer in
      male rats. Rats were randomly assigned into three groups: intact group, gastric
      ulcer group and Aloe vera group (treatment with Aloe vera following gastric ulcer
      induction). The acid levels and brain and intestinal water content of each sample
      were measured eight days after the gastric ulcer induction. RESULTS: Gastric acid
      levels were significantly decreased in Aloe vera group when compared with gastric
      ulcer group (p<0.05). However, there were no differences in acid output between
      gastric ulcer and Aloe vera groups with intact group. After Aloe vera
      administration, the amount of brain water content had no difference with intact
      and gastric ulcer groups (p<0.05). The duodenal water content in Aloe vera group
      was significantly reduced compared with intact group (p<0.05) but gastric ulcer
      group had no significant difference with intact and Aloe vera group. CONCLUSIONS:
      The administration of Aloe vera has an inhibitory effect on the gastric acid
      output.

PMID- 25050312
TI  - The effect of hydroalcoholic extract and essential oil of Heracleum persicum on
      lipid profile in cholesterol-fed rabbits.
AB  - OBJECTIVE: This study was designed to investigate the effect of hydroalcoholic
      extract and essential oil of Heracleum persicum (Apiaceae) on lipid profile of
      male hyperlipidemic rabbits. MATERIALS AND METHODS: Thirty rabbits were randomly
      divided into six groups of five each. One group received normal diet and the
      other groups fed with a high cholesterol (2% W/W) diet for 7 weeks. Vehicle,
      hydroalcoholic extract (500 and 1000 mg/kg), essential oil (200  l/kg), and
      lovastatin (5 mg/kg) were administered orally to animals and their effects on
      lipid profile were evaluated. RESULTS: Essential oil of H. perscum significantly
      (p<0.05) lowered serum triglyceride level and increased HDL-cholesterol
      concentration. Moreover, hydroalcoholic extract (1000 mg/kg), essential oil (200 
      l/kg), and lovastatin significantly (p<0.01) reduced serum concentration of total
      cholesterol and LDL-cholesterol. CONCLUSION: These findings suggest that
      essential oil of the plant fruits may have some benefits in reducing
      cardiovascular risk factors.

PMID- 25050313
TI  - Evaluation of anti-urolithiatic effect of aqueous extract of Bryophyllum pinnatum
      (Lam.) leaves using ethylene glycol-induced renal calculi.
AB  - Materials and Methods : Thirty-six Wistar male rats were randomly divided into
      six equal groups. Group A animals received distilled water for 28 days. Group B
      to group F animals received 1% v/v ethylene glycol in distilled water for 28 days
      and group B served as ethylene glycol control. Groups C and D (preventive groups)
      received aqueous extract of leaves of B. pinnatum 50 and 100 mg/kg
      intraperitoneally, respectively for 28 days. Groups E and F (treatment groups)
      received aqueous extract of leaves of B. pinnatum 50 and 100 mg/kg
      intraperitoneally, respectively from 15(th) to 28(th) day. On days 0 and 28, 24
      hrs urine samples were collected for urinary volume and urinary oxalate
      measurement. On day 28, blood was collected for serum creatinine and blood urea
      level monitoring. All animals were sacrificed and kidneys were removed, weighed,
      and histopathologically evaluated for calcium oxalate crystals deposition.
      RESULTS: Administration of aqueous extract of leaves of B. pinnatum reduced urine
      oxalate level  significantly, as compared with Group B (p<0.001). Serum
      creatinine and blood urea level were  improved significantly in all aqueous
      extract of leaves of B. pinnatum-treated groups. Relative  kidney weight and
      calcium oxalate depositions were found significantly reduced in animals  received
      ABP as compared with Group B (p<0.001).  CONCLUSIONS: B. pinnatum is effective in
      prevention and treatment of ethylene glycol-induced urolithiasis.

PMID- 25050314
TI  - Treatment of hypercholesterolemia: screening of Solanum macrocarpon Linn
      (Solanaceae) as a medicinal plant in Benin.
AB  - OBJECTIVE: Hypercholesterolemia is the greatest risk factor for cardiovascular
      diseases. The present study is conducted to evaluate the lipid lowering activity
      of leaves and fruits of Solanum macrocarpon, a vegetable, on Wistar rats
      experimentally rendered hypercholesterolemic by Triton X-100. MATERIALS AND
      METHODS: The leaves and fruits were administered (p.o.) for 7 days to rats at
      doses of 400 and 800 mg/kg of body weight. Atorvastatin was used as reference
      treatment drug. The data were analyzed by the Brown-Forsythe ANOVA, Dunnett's T3
      multiple comparison test, and Dunnett's t test. All tests were done at the 5%
      significance level. RESULTS: Administration of S. macrocarpon (fruits as well as
      leaves) resulted in a statistically significant decrease in total cholesterol,
      LDL-cholesterol, VLDL-cholesterol, and triglycerides in the treated groups
      compared with the untreated hypercholesterolemic group, regardless of the
      administrated doses. A significant increase in HDL-cholesterol was observed in
      the treated groups. Hepatic disorders due to the Triton have been corrected by S.
      macrocarpon. CONCLUSIONS: This vegetable effectively suppresses experimental
      hypercholesterolemia in Wistar rats, suggesting a protective role in
      cardiovascular diseases. Its use by individuals at risk should be promoted.

PMID- 25050315
TI  - Silymarin attenuates mycophenolate mofetil-induced duodenal disorders in rats.
AB  - OBJECTIVE: The protective effect of silymarin (SMN) on mycophenolate mofetil
      (MMF)-induced duodenal disorders was investigated. MATERIALS AND METHODS: Forty
      two Wistar rats were assigned to seven groups including control and test groups.
      The control animals received saline and the test animals were treated with MMF
      (30 mg/kg, orally) and saline, MMF and SMN (25, 50, and 100 mg/kg, orally), MMF
      and Celecoxib (CLX, 50 mg/kg, orally), and MMF and SMN plus CLX for 14
      consecutive days. The antioxidant status and myeloperoxidase activity were
      determined and the histopathological examinations on duodenal section also were
      performed. RESULTS: Biochemical analyses revealed that SMN and CLX individually
      and in combination therapy could reduce the MMF-increased nitric oxide (NO)
      content, myeloperoxidase (MPA) activity, and malondialdehyde (MDA) level, while
      the MMF-reduced level of total thiol molecules (TTM) was increased significantly
      (p<0.05) by given compounds. Concurrent administration of SMN and CLX resulted in
      a synergistic effect on the reduction of MDA level and MPO activity. SMN and CLX
      were able to improve the MMF-induced histopathological damages including the
      villus atrophy and inflammatory cells infiltration. CONCLUSION: Our data suggest
      that the MMF-induced duodenal disorders may attribute to the elevated NO and MDA
      levels and myeloperoxidase activity that resulted in pathological injuries.
      Moreover, the biochemical alterations and histopathological injuries due to MMF
      administration were reduced by SMN alone or in combination with CLX indicating
      its protective effect.

PMID- 25050316
TI  - Mineral elements and essential oil contents of Scutellaria luteo-caerulea Bornm.
      & Snit.
AB  - OBJECTIVE: Scutellaria luteo-caerulea Bornm. & Snit. is one of the species of
      genus Scutellaria, within the family of the Lamiaceae, that is used for immune
      system stimulation and antibacterial effects in traditional medicine in Iran. The
      aims of this study were to analyze essential oils and mineral element contents of
      leaves of S. luteo-caerulea in flowering stage of development. MATERIALS AND
      METHODS: The essential oils were obtained by hydrodistillation of the leaves of
      S. luteo-caerulea and were analyzed by gas chromatography mass spectrometry
      (GC/MS). Moreover, microwave digestion with atomic absorption spectrophotometry
      were used for the mineral elements assay. RESULTS: Ninety-seven constituents were
      detected. Between them, the major components were trans-caryophyllene (25.4%), D
      germacrene (7.9%), and linalool (7.4%). Determination of mineral elements showed
      that the highest minerals were Ca(2+) (65.14+/-1.95 ug/ml) and K(+) (64.67+/-3.10
      ug/ml). CONCLUSION: Presence of different essential oils and rich sources of
      Ca(2+) and K(+) candidate this plant as an auxiliary medication in different
      diseases, but more complementary researches are needed about its potency and side
      effects.

PMID- 25050317
TI  - Chemical composition of essential oil and anti trichomonas activity of leaf,
      stem, and flower of Rheum ribes L. extracts.
AB  - OBJECTIVES: Trichomoniasis is one of the most common sexually transmitted
      diseases in humans and is caused by the protozoan Trichomonas vaginalis.
      Nowadays, increasing resistance to drugs such as metronidazole resulted in many
      problem, so new effective remedies are needed. In this study, we evaluate
      constituents of essential oil and anti-trichomonas activity of Rheum ribes.
      MATERIALS AND METHODS: The essential oil from Rheum ribes L. flower growing wild
      in Iran was analyzed by GC/MS. The parasites were treated with different extract
      and fractions of the flower, stem, and leave of the plant. Anti-trichomonas
      activity was evaluated using an in vitro assay. RESULTS: In all, 19 compounds
      were identified; palmitic acid [27.08%], n-eicosane [9.9%], n-tetracosane
      [7.34%], linoleic acid [6.56%], and ethyl linoleate [4.76%] were the main
      components of the oil. Rheum ribes extracts and fractions concentration
      dependently inhibited the ability of parasites to growth. This was associated
      with polarity of solvent used for fractionation and plant parts used for
      extraction. CONCLUSION: Findings demonstrate the potential of Rheum ribes
      extracts as an anti-trichomonas agent for human use. Further studies are required
      to evaluate its toxicity and safety.

PMID- 25050318
TI  - Chemical composition, antibacterial and antioxidant profile of essential oil from
      Murraya koenigii (L.) leaves.
AB  - OBJECTIVE: This study is designed to extract and examine chemical composition,
      antimicrobial and antioxidant activity of the hydro-distillated essential oil of
      Murraya koenigii leaves from the south region of Tamilnadu, India. Matherials and
      Methods: Gas Chromatography (GC) and Gas Chromatography-Mass Spectrometry (GC-MS)
      analysis of the essential oil result was indicates the 33 different compounds
      representing 97.56 % of the total oil. RESULTS: Major compounds detected in the
      oil were Linalool (32.83%), Elemol (7.44%), Geranyl acetate (6.18%), Myrcene
      (6.12%), Allo-Ocimene (5.02), alpha-Terpinene (4.9%), and (E)-beta-Ocimene
      (3.68%) and Neryl acetate (3.45%). From the identified compounds, they were
      classified into four groups that are oxygenated monoterpenes (72.15%),
      monoterpene hydrocarbons (11.81%), oxygenated sesquiterpenes (10.48%) and
      sesquiterpenes hydrocarbons (03.12%). The antibacterial activity of essential oil
      has pronounced by Disc Diffusion Method against various pathogenic microbes.
      CONCLUSION: The oil has a maximum zone of inhibition ability against
      Corynebacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus pyogenes,
      Klebsiella pneumonia and Enterobacter aerogenes. The antioxidant profile of the
      sample was determined by different test systems. In all the systems, essential
      oil showed a strongest activity profile within the concentration range.

PMID- 25050319
TI  - Preliminary pharmacological activity of the methanolic extract of Premna
      integrifolia barks in rats.
AB  - OBJECTIVE: Premna integrifolia Linn (Family: Verbenaceae) synonym of Premna
      serratifolia has tremendous medicinal value. Preliminary pharmacological studies
      were performed on the methanolic extract of Premna integrifolia (MEPI) bark to
      investigate neuropharmacological, analgesic, and anti-inflammatory activities.
      MATERIALS AND METHODS: Neuropharmacology study was done by open field and hole
      cross test whereas acetic acid writhing test and formalin induced pain was done
      for analgesic activity of MEPI. Carrageenan induced inflammatory model was
      considered for anti-inflammatory activity evaluation. RESULTS: A statistically
      significant (p0.05) decrease in locomotor activity was observed at all doses in
      the open-field and hole-cross tests. The extract significantly (p0.05) and dose
      dependently reduced the writhing reflex in the acetic acid-induced writhing test
      as well as licking response in the formalin induced inflammatory pain. At 200
      mg/kg body weight dose, MEPI showed 71.16% inhibition in carrageenan induced anti
      inflammatory activity. CONCLUSION: The finding of this study suggests that MEPI
      will provide scientific support for the use of this species in traditional
      medicine.

PMID- 25050320
TI  - An emerging molecular understanding and novel targeted treatment approaches in
      pediatric kidney diseases.
AB  - The evaluation and treatment of the heterogeneous group of kidney diseases poses
      a challenging field in pediatrics. Many of the pediatric disorders resulting in
      severe renal affection are exceedingly rare and therapeutic approaches have
      remained symptomatic for most of these disease entities. The insights obtained
      from cellular and molecular studies of rare disorders by recent genetic studies
      have now substantially changed our mechanistic understanding of various important
      pediatric renal diseases and positive examples of targeted treatment approaches
      are emerging. Three fields of recent breathtaking developments in pediatric
      nephrology are the pathophysiology of nephrotic syndrome and proteinuria, the
      molecular mechanisms underlying atypical hemolytic uremic syndrome, and the
      genetics and cellular biology of inherited cystic kidney diseases. In all three
      areas, the combined power of molecular basic science together with deeply
      characterizing clinical approaches has led to the establishment of novel
      pathophysiological principles and to the first clinical trials of targeted
      treatment approaches. 

PMID- 25050321
TI  - Telemonitoring with respect to mood disorders and information and communication
      technologies: overview and presentation of the PSYCHE project.
AB  - This paper reviews what we know about prediction in relation to mood disorders
      from the perspective of clinical, biological, and physiological markers. It then
      also presents how information and communication technologies have developed in
      the field of mood disorders, from the first steps, for example, the transition
      from paper and pencil to more sophisticated methods, to the development of
      ecological momentary assessment methods and, more recently, wearable systems.
      These recent developments have paved the way for the use of integrative
      approaches capable of assessing multiple variables. The PSYCHE project stands for
      Personalised monitoring SYstems for Care in mental HEalth. 

PMID- 25050322
TI  - Metformin against cancer stem cells through the modulation of energy metabolism:
      special considerations on ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecologic malignancy among women worldwide
      and is presumed to result from the presence of ovarian cancer stem cells. To
      overcome the limitation of current anticancer agents, another anticancer strategy
      is necessary to effectively target cancer stem cells in ovarian cancer. In many
      types of malignancies, including ovarian cancer, metformin, one of the most
      popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and
      anticancer efficacy with respect to incidence and overall survival rates. Thus,
      the metabolic reprogramming of cancer and cancer stem cells driven by genetic
      alterations during carcinogenesis and cancer progression could be therapeutically
      targeted. In this review, the potential efficacy and anticancer mechanisms of
      metformin against ovarian cancer stem cells will be discussed. 

PMID- 25050323
TI  - Sinefungin, a natural nucleoside analogue of S-adenosylmethionine, inhibits
      Streptococcus pneumoniae biofilm growth.
AB  - Pneumococcal colonization and disease is often associated with biofilm formation,
      in which the bacteria exhibit elevated resistance both to antibiotics and to host
      defense systems, often resulting in infections that are persistent and difficult
      to treat. We evaluated the effect of sinefungin, a nucleoside analogue of S
      adenosylmethionine, on pneumococcal in vitro biofilm formation and in vivo
      colonization. Sinefungin is bacteriostatic to pneumococci and significantly
      decreased biofilm growth and inhibited proliferation and structure of actively
      growing biofilms but did not alter growth or the matrix structure of established
      biofilms. Sinefungin significantly reduced pneumococcal colonization in rat
      middle ear. The quorum sensing molecule (autoinducer-2) production was
      significantly reduced by 92% in sinefungin treated samples. The luxS, pfs, and
      speE genes were downregulated in biofilms grown in the presence of sinefungin.
      This study shows that sinefungin inhibits pneumococcal biofilm growth in vitro
      and colonization in vivo, decreases AI-2 production, and downregulates luxS, pfs,
      and speE gene expressions. Therefore, the S-adenosylmethionine (SAM) inhibitors
      could be used as lead compounds for the development of novel antibiofilm agents
      against pneumococci. 

PMID- 25050324
TI  - A study on decoding models for the reconstruction of hand trajectories from the
      human magnetoencephalography.
AB  - Decoding neural signals into control outputs has been a key to the development of
      brain-computer interfaces (BCIs). While many studies have identified neural
      correlates of kinematics or applied advanced machine learning algorithms to
      improve decoding performance, relatively less attention has been paid to optimal
      design of decoding models. For generating continuous movements from neural
      activity, design of decoding models should address how to incorporate movement
      dynamics into models and how to select a model given specific BCI objectives.
      Considering nonlinear and independent speed characteristics, we propose a hybrid
      Kalman filter to decode the hand direction and speed independently. We also
      investigate changes in performance of different decoding models (the linear and
      Kalman filters) when they predict reaching movements only or predict both reach
      and rest. Our offline study on human magnetoencephalography (MEG) during point-to
      point arm movements shows that the performance of the linear filter or the Kalman
      filter is affected by including resting states for training and predicting
      movements. However, the hybrid Kalman filter consistently outperforms others
      regardless of movement states. The results demonstrate that better design of
      decoding models is achieved by incorporating movement dynamics into modeling or
      selecting a model according to decoding objectives. 

PMID- 25050326
TI  - Testing of visual field with virtual reality goggles in manual and visual grasp
      modes.
AB  - Automated perimetry is used for the assessment of visual function in a variety of
      ophthalmic and neurologic diseases. We report development and clinical testing of
      a compact, head-mounted, and eye-tracking perimeter (VirtualEye) that provides a
      more comfortable test environment than the standard instrumentation. VirtualEye
      performs the equivalent of a full threshold 24-2 visual field in two modes: (1)
      manual, with patient response registered with a mouse click, and (2) visual
      grasp, where the eye tracker senses change in gaze direction as evidence of
      target acquisition. 59 patients successfully completed the test in manual mode
      and 40 in visual grasp mode, with 59 undergoing the standard Humphrey field
      analyzer (HFA) testing. Large visual field defects were reliably detected by
      VirtualEye. Point-by-point comparison between the results obtained with the
      different modalities indicates: (1) minimal systematic differences between
      measurements taken in visual grasp and manual modes, (2) the average standard
      deviation of the difference distributions of about 5 dB, and (3) a systematic
      shift (of 4-6 dB) to lower sensitivities for VirtualEye device, observed mostly
      in high dB range. The usability survey suggested patients' acceptance of the head
      mounted device. The study appears to validate the concepts of a head-mounted
      perimeter and the visual grasp mode.

PMID- 25050325
TI  - Oxygen radicals elicit paralysis and collapse of spinal cord neuron growth cones
      upon exposure to proinflammatory cytokines.
AB  - A persistent inflammatory and oxidative stress is a hallmark of most chronic CNS
      pathologies (Alzheimer's (ALS)) as well as the aging CNS orchestrated by the
      proinflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interleukin
      1 beta (IL-1beta). Loss of the integrity and plasticity of neuronal morphology
      and connectivity comprises an early step in neuronal degeneration and ultimate
      decline of cognitive function. We examined in vitro whether TNFalpha or IL-1beta
      impaired morphology and motility of growth cones in spinal cord neuron cultures.
      TNFalpha and IL-1beta paralyzed growth cone motility and induced growth cone
      collapse in a dose-dependent manner reflected by complete attenuation of neurite
      outgrowth. Scavenging reactive oxygen species (ROS) or inhibiting NADPH oxidase
      activity rescued loss of neuronal motility and morphology. TNFalpha and IL-1beta
      provoked rapid, NOX-mediated generation of ROS in advancing growth cones, which
      preceded paralysis of motility and collapse of morphology. Increases in ROS
      intermediates were accompanied by an aberrant, nonproductive reorganization of
      actin filaments. These findings suggest that NADPH oxidase serves as a pivotal
      source of oxidative stress in neurons and together with disruption of actin
      filament reorganization contributes to the progressive degeneration of neuronal
      morphology in the diseased or aging CNS. 

PMID- 25050327
TI  - On designing multicore-aware simulators for systems biology endowed with OnLine
      statistics.
AB  - The paper arguments are on enabling methodologies for the design of a fully
      parallel, online, interactive tool aiming to support the bioinformatics
      scientists .In particular, the features of these methodologies, supported by the
      FastFlow parallel programming framework, are shown on a simulation tool to
      perform the modeling, the tuning, and the sensitivity analysis of stochastic
      biological models. A stochastic simulation needs thousands of independent
      simulation trajectories turning into big data that should be analysed by
      statistic and data mining tools. In the considered approach the two stages are
      pipelined in such a way that the simulation stage streams out the partial results
      of all simulation trajectories to the analysis stage that immediately produces a
      partial result. The simulation-analysis workflow is validated for performance and
      effectiveness of the online analysis in capturing biological systems behavior on
      a multicore platform and representative proof-of-concept biological systems. The
      exploited methodologies include pattern-based parallel programming and data
      streaming that provide key features to the software designers such as performance
      portability and efficient in-memory (big) data management and movement. Two
      paradigmatic classes of biological systems exhibiting multistable and oscillatory
      behavior are used as a testbed. 

PMID- 25050328
TI  - Plant-derived antimicrobials reduce E. coli O157:H7 virulence factors critical
      for colonization in cattle gastrointestinal tract in vitro.
AB  - This study investigated the effect of subinhibitory concentrations (SIC) of five
      plant-derived antimicrobials (PDAs), namely, trans cinnamaldehyde, eugenol,
      carvacrol, thymol, and beta-resorcylic acid, on E. coli O157:H7 (EHEC) attachment
      and invasion of cultured bovine colonic (CO) and rectoanal junction (RAJ)
      epithelial cells. In addition, PDAs' effect on EHEC genes critical for
      colonization of cattle gastrointestinal tract (CGIT) was determined in bovine
      rumen fluid (RF) and intestinal contents (BICs). Primary bovine CO and RAJ
      epithelial cells were established and were separately inoculated with three EHEC
      strains with or without (control) SIC of each PDA. Following incubation, EHEC
      that attached and invaded the cells were determined. Furthermore, the expression
      of EHEC genes critical for colonization in cattle was investigated using real
      time, quantitative polymerase chain reaction in RF and BICs. All the PDAs
      decreased EHEC invasion of CO and RAJ epithelial cells (P < 0.05). The PDAs also
      downregulated (P < 0.05) the expression of EHEC genes critical for colonization
      in CGIT. Results suggest that the PDAs could potentially be used to control EHEC
      colonization in cattle; however follow-up in vivo studies in cattle are
      warranted. 

PMID- 25050329
TI  - Potential probiotic Escherichia coli 16 harboring the Vitreoscilla hemoglobin
      gene improves gastrointestinal tract colonization and ameliorates carbon
      tetrachloride induced hepatotoxicity in rats.
AB  - The present study describes the beneficial effects of potential probiotic E. coli
      16 (pUC8:16gfp) expressing Vitreoscilla hemoglobin (vgb) gene, associated with
      bacterial respiration under microaerobic condition, on gastrointestinal (GI)
      colonization and its antioxidant activity on carbon tetrachloride (CCl4) induced
      toxicity in Charles Foster rats. In vitro, catalase activity in E. coli 16
      (pUC8:16gfp) was 1.8 times higher compared to E. coli 16 (pUC-gfp) control. In
      vivo, E. coli 16 (pUC8:16gfp) not only was recovered in the fecal matter after 70
      days of oral administration but also retained antibacterial activities, whereas
      E. coli 16 (pUC-gfp) was not detected. Oral administration of 200 and 500 MUL/kg
      body weight of CCl4 to rats at weekly interval resulted in elevated serum
      glutamyl pyruvate transaminase (SGPT) and serum glutamyl oxalacetate transaminase
      (SGOT) levels compared to controls. Rats prefed with E. coli 16 (pUC8:16gfp)
      demonstrated near to normal levels for SGPT and SGOT, whereas the liver
      homogenate catalase activity was significantly increased compared to CCl4 treated
      rats. Thus, pUC8:16gfp plasmid encoding vgb improved the growth and GI tract
      colonization of E. coli 16. In addition, it also enhanced catalase activity in
      rats harboring E. coli 16 (pUC8:16gfp), thereby preventing the absorption of CCl4
      to GI tract.

PMID- 25050330
TI  - Advances in neuromotor stroke rehabilitation.

PMID- 25050331
TI  - Changes in osteoblastic activity in patient who received bortezomib as second
      line treatment for plasma cell myeloma: a prospective multicenter study.
AB  - We conducted a prospective multicenter study identifying the role of bortezomib
      in patients with relapsed or refractory plasma cell myeloma (PCM) in bone
      resorption and formation via bone turnover markers. A total of 104 patients
      received at least 1 cycle of bortezomib. Most of them had advanced disease (n =
      89). Among them, 75 patients completed 4 cycles of treatment. Most of the
      patients (81.7%) were treated in combination with steroid. After the 4th cycle
      treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26
      patients achieved less than PR (35.6%). The proportion of patients who achieved
      >= PR increased as patients received more treatment cycles, reaching 90% after
      the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation
      markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased
      significantly. These findings were observed primarily in patients who received
      steroid and who had a longer disease duration. While sRANKL demonstrated
      significant reduction posttreatment, osteoprotegerin (OPG) level did not
      significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P
      = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib
      and steroid may rearrange the metabolic balance between osteoblast and osteoclast
      activities in PCM. 

PMID- 25050332
TI  - Neuromodulatory effects of hesperidin in mitigating oxidative stress in
      streptozotocin induced diabetes.
AB  - Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ-)
      induced diabetes mellitus and its complication in central nervous system (CNS).
      Recent studies have provided insights on antioxidants and their emergence as
      potential therapeutic and nutraceutical. The present study examined the
      hypothesis that hesperidin (HP) ameliorates oxidative stress and may be a
      limiting factor in the extent of CNS complication following diabetes. To test
      this hypothesis rats were divided into four groups: control, diabetic, diabetic
      HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by
      a single injection of STZ (65 mg/kg body weight). Three days after STZ injection,
      HP was given (50 mg/kg b.wt. orally) once daily for four weeks. The results of
      the present investigation suggest that the significant elevated levels of
      oxidative stress markers were observed in STZ-treated animals, whereas
      significant depletion in the activity of nonenzymatic antioxidants and enzymatic
      antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker
      activity was also altered significantly. HP treatment significantly attenuated
      the altered levels of oxidative stress and neurotoxicity biomarkers. Our results
      demonstrate that HP exhibits potent antioxidant and neuroprotective effects on
      the brain tissue against the diabetic oxidative damage in STZ-induced rodent
      model.

PMID- 25050333
TI  - The diagnostic value of cervical lymph node metastasis in head and neck squamous
      carcinoma by using diffusion-weighted magnetic resonance imaging and computed
      tomography perfusion.
AB  - PURPOSE: The aim of this study was to compare diffusion-weighted magnetic
      resonance imaging (DWI) with computed tomography perfusion (CTP) for preoperative
      detection of metastases to lymph nodes (LNs) in head and neck squamous cell
      carcinoma (SCC). METHODS: Between May 2010 and April 2012, 30 patients with head
      and neck SCC underwent preoperative DWI and CTP. Two radiologists measured
      apparent diffusion coefficient (ADC) values and CTP parameters independently.
      Surgery and histopathologic examinations were performed on all patients. RESULTS:
      On DWI, 65 LNs were detected in 30 patients. The mean ADC value of metastatic
      nodes was lower than benign nodes and the difference was statistically
      significant (P < 0.05). On CTP images, the mean value in metastatic nodes of
      blood flow (BF) and blood volume (BV) was higher than that in benign nodes, and
      mean transit time (MTT) in metastatic nodes was lower than that in benign nodes.
      There were significant differences in BF and MTT values between metastatic and
      benign LNs (P < 0.05). There were significant differences between the AUCs of DWI
      and CTP (Z=4.612, P < 0.001). CONCLUSION: DWI with ADC value measurements may be
      more accurate than CTP for the preoperative diagnosis of cervical LN metastases.

PMID- 25050334
TI  - Administration of the resveratrol analogues isorhapontigenin and heyneanol-A
      protects mice hematopoietic cells against irradiation injuries.
AB  - Ionizing radiation (IR) is known not only to cause acute bone marrow (BM)
      suppression but also to lead to long-term residual hematopoietic injury. These
      effects have been attributed to IR inducing the generation of reactive oxygen
      species (ROS) in hematopoietic cells. In this study, we examined if
      isorhapontigenin and heyneanol-A, two analogues of resveratrol, could mitigate IR
      induced BM suppression. The results of cell viability assays, clonogenic assays,
      and competitive repopulation assays revealed that treatment with these compounds
      could protect mice BM mononuclear cells (BMMNC), hematopoietic progenitor cells,
      and hematopoietic stem cells from IR-induced BM suppression. Moreover, the
      expression of genes related to the endogenous cellular antioxidant system in
      hematopoietic cells was analyzed. The expression and activity of SOD2 and GPX1
      were found to be decreased in irradiated BMMNC, and the application of the
      resveratrol analogues could ameliorate this damage. Our results suggest that in
      comparison with resveratrol and isorhapontigenin, treatment with heyneanol-A can
      protect hematopoietic cells from IR-induced damage to a greater degree; the
      protective effects of these compounds are probably the result of their
      antioxidant properties. 

PMID- 25050335
TI  - Dual binding site and selective acetylcholinesterase inhibitors derived from
      integrated pharmacophore models and sequential virtual screening.
AB  - In this study, we have employed in silico methodology combining double
      pharmacophore based screening, molecular docking, and ADME/T filtering to
      identify dual binding site acetylcholinesterase inhibitors that can
      preferentially inhibit acetylcholinesterase and simultaneously inhibit the
      butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D
      pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from
      xanthostigmine derivatives through HypoGen and validated using test set,
      Fischer's randomization technique. The best acetylcholinesterase and
      butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B,
      with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D
      query for screening the Zinc database. The screened hits were then subjected to
      the ADME/T and molecular docking study to prioritise the compounds. Finally, 18
      compounds were identified as potential leads against AChE enzyme, showing good
      predicted activities and promising ADME/T properties. 

PMID- 25050336
TI  - Morphometric evaluation of preeclamptic placenta using light microscopic images.
AB  - Deficient trophoblast invasion and anomalies in placental development generally
      lead to preeclampsia (PE) but the inter-relationship between placental function
      and morphology in PE still remains unknown. The aim of this study was to evaluate
      the morphometric features of placental villi and capillaries in preeclamptic and
      normal placentae. The study included light microscopic images of placental tissue
      sections of 40 preeclamptic and 35 normotensive pregnant women. Preprocessing and
      segmentation of these images were performed to characterize the villi and
      capillaries. Fisher's linear discriminant analysis (FLDA), hierarchical cluster
      analysis (HCA), and principal component analysis (PCA) were applied to identify
      the most significant placental (morphometric) features from microscopic images. A
      total of 10 morphometric features were extracted, of which the villous parameters
      were significantly altered in PE. FLDA identified 5 highly significant
      morphometric features (>90% overall discrimination accuracy). Two large
      subclusters were clearly visible in HCA based dendrogram. PCA returned three most
      significant principal components cumulatively explaining 98.4% of the total
      variance based on these 5 significant features. Hence, quantitative microscopic
      evaluation revealed that placental morphometry plays an important role in
      characterizing PE, where the villous is the major component that is affected. 

PMID- 25050337
TI  - Myorelaxant effect of bee venom topical skin application in patients with RDC/TMD
      Ia and RDC/TMD Ib: a randomized, double blinded study.
AB  - The aim of the study was the evaluation of myorelaxant action of bee venom (BV)
      ointment compared to placebo. Parallel group, randomized double blinded trial was
      performed. Experimental group patients were applying BV for 14 days, locally over
      masseter muscles, during 3-minute massage. Placebo group patients used vaseline
      for massage. Muscle tension was measured twice (TON1 and TON2) in rest muscle
      tonus (RMT) and maximal muscle contraction (MMC) on both sides, right and left,
      with Easy Train Myo EMG (Schwa-medico, Version 3.1). Reduction of muscle tonus
      was statistically relevant in BV group and irrelevant in placebo group. VAS scale
      reduction was statistically relevant in both groups: BV and placebo.
      Physiotherapy is an effective method for myofascial pain treatment, but 0,0005%
      BV ointment gets better relief in muscle tension reduction and analgesic effect.
      This trial is registered with Clinicaltrials.gov NCT02101632. 

PMID- 25050338
TI  - Animal arterivirus infections.

PMID- 25050339
TI  - Bioactivity-guided fractionation identifies amygdalin as a potent neurotrophic
      agent from herbal medicine Semen Persicae extract.
AB  - Herbal medicine Semen Persicae is widely used to treat blood stasis in Chinese
      medicine and other oriental folk medicines. Although little is known about the
      effects of Semen Persicae and its active compounds on neuron differentiation, our
      pilot study showed that Semen Persicae extract promoted neurite outgrowth in rat
      dopaminergic PC12 cells. In the present study, we developed a bioactivity-guided
      fractionation procedure for the characterization of the neurotrophic activity of
      Semen Persicae extract. The resultant fractions were assayed for neurite
      outgrowth in PC12 cells based on microscopic assessment. Through liquid-liquid
      extraction and reverse phase HPLC separation, a botanical glycoside amygdalin was
      isolated as the active compound responsible for the neurotrophic activity of
      Semen Persicae extract. Moreover, we found that amygdalin rapidly induced the
      activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). A specific
      ERK1/2 inhibitor PD98059 attenuated the stimulatory effect of amygdalin on
      neurite outgrowth. Taken together, amygdalin was identified as a potent
      neurotrophic agent from Semen Persicae extract through a bioactivity-guided
      fractional procedure. The neurotrophic activity of amygdalin may be mediated by
      the activation of ERK1/2 pathway. 

PMID- 25050340
TI  - The effects of intravenous fosaprepitant and ondansetron for the prevention of
      postoperative nausea and vomiting in neurosurgery patients: a prospective,
      randomized, double-blinded study.
AB  - The incidence of postoperative nausea and vomiting (PONV) is 30-50% after
      surgery. PONV occurs frequently, especially after craniotomy. In this study, we
      investigated the preventive effects on PONV in a randomized study by comparing
      patients who had been administered fosaprepitant, a neurokinin-1 (NK1) receptor
      antagonist, or ondansetron intravenously. Sixty-four patients undergoing
      craniotomy were randomly allocated to receive fosaprepitant 150 mg i.v. (NK1
      group, n = 32) or ondansetron 4 mg i.v. (ONS group, n = 32) before anesthesia.
      The incidence of vomiting was significantly less in the NK1 group, where 2 of 32
      (6%) patients experienced vomiting compared to 16 of 32 (50%) patients in the ONS
      group during the first 24 and 48 hours following surgery. Additionally, the
      incidence of complete response (no vomiting and no rescue antiemetic use) was
      significantly higher in the NK1 group than in the ONS group, and was 66% versus
      41%, respectively, during the first 24 hours, and 63% versus 38%, respectively,
      during the first 48 hours. In patients undergoing craniotomy, fosaprepitant is
      more effective than ondansetron in increasing the rate of complete response and
      decreasing the incidence of vomiting at 24 and 48 hours postoperatively.

PMID- 25050341
TI  - Evidence of inflammatory system involvement in Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disease underpinned by
      both genetic and environmental etiologic factors. Recent findings suggest that
      inflammation may be a pathogenic factor in the onset and progression of both
      familial and sporadic PD. Understanding the precise role of inflammatory factors
      in PD will likely lead to understanding of how the disease arises. In vivo
      evidence for inflammation in PD includes dysregulated molecular mediators such as
      cytokines, complement system and its receptors, resident microglial activation,
      peripheral immune cells invasion, and altered composition and phenotype of
      peripheral immune cells. The growing awareness of these factors has prompted
      novel approaches to modulate the immune system, although it remains whether these
      approaches can be used in humans. Influences of ageing and differential exposure
      to environmental agents suggest potential host-pathogen specific pathophysiologic
      factors. There is a clear need for research to further unravel the
      pathophysiologic role of immunity in PD, with the potential of developing new
      therapeutic targets for this debilitating condition. 

PMID- 25050343
TI  - Prenatal ultrasound screening for external ear abnormality in the fetuses.
AB  - OBJECTIVES: To investigate the best time of examination and section chosen of
      routine prenatal ultrasound screening for external ear abnormalities and evaluate
      the feasibility of examining the fetal external ear with ultrasonography.
      METHODS: From July 2010 until August 2011, 42118 pregnant women with single fetus
      during 16-40 weeks of pregnancy were enrolled in the study. Fetal auricles and
      external auditory canal in the second trimester of pregnancy were evaluated by
      routine color Doppler ultrasound screening and systematic screening. Ultrasound
      images of fetal external ears were obtained on transverse-incline view at
      cervical vertebra level and mandible level and on parasagittal view and coronal
      view at external ear level. RESULTS: Five fetuses had anomalous ears including
      bilateral malformed auricles with malformed external auditory canal, unilateral
      deformed external ear, and unilateral microtia. The detection rate of both
      auricles was negatively correlated with gestational age. Of the 5843 fetuses
      undergoing a routine ultrasound screening, 5797 (99.21%) had bilateral auricles.
      Of the 4955 fetuses following systematic screening, all fetuses (100%) had
      bilateral auricles. The best time for fetal auricles observation with
      ultrasonography is 20-24 weeks of pregnancy. CONCLUSIONS: Detection of external
      ear abnormalities may assist in the diagnosis of chromosomal abnormalities.

PMID- 25050342
TI  - Simultaneous changes of spatial memory and spine density after intrahippocampal
      administration of fibrillar abeta1-42 to the rat brain.
AB  - Several animal models of Alzheimer's disease have been used in laboratory
      experiments. Intrahippocampal injection of fibrillar amyloid-beta (fAbeta)
      peptide represents one of the most frequently used models, mimicking Abeta
      deposits in the brain. In our experiment synthetic fAbeta1-42 peptide was
      administered to rat hippocampus. The effect of the Abeta peptide on spatial
      memory and dendritic spine density was studied. The fAbeta1-42-treated rats
      showed decreased spatial learning ability measured in Morris water maze (MWM).
      Simultaneously, fAbeta1-42 caused a significant reduction of the dendritic spine
      density in the rat hippocampus CA1 region. The decrease of learning ability and
      the loss of spine density were in good correlation. Our results prove that both
      methods (MWM and dendritic spine density measurement) are suitable for studying
      Abeta-triggered neurodegeneration processes.

PMID- 25050344
TI  - Biomolecular networks and human diseases.

PMID- 25050346
TI  - MicroRNA era: the importance for diagnosis and prognosis of adrenocortical
      tumors.
AB  - MicroRNAs play an essential role in posttranscriptional regulation of gene
      expression. They are evolutionary conserved, small, noncoding, 19-22-nucleotide
      RNAs, whose abnormalities, such as up- or downregulated expression, have been
      associated with several neoplasms, including adrenocortical tumors. Expression
      levels of distinct microRNAs can distinguish benign from malignant adrenal
      tumors. This current review provides recent data on the miRNAs profile in benign
      and malignant adrenocortical tumors diagnosed in adult and pediatric patients. 

PMID- 25050345
TI  - Nongenetic determinants of age at menarche: a systematic review.
AB  - BACKGROUND: The acceleration of pubertal development is an important medical and
      social problem, as it may result in increased morbidity and mortality in later
      life. This systematic review summarizes relevant data about nongenetic factors,
      which contribute to age at menarche (AAM), and suggests those which may be the
      most important. METHODS: The available literature from 1980 till July 2013 was
      searched using PubMed and Google Scholar databases. Finally, 154 papers were
      selected for the analysis. RESULTS: Environmental factors, which may affect AAM,
      vary in populations of different ethnicity. The prenatal, infancy, and early
      childhood periods are the most susceptible to these factors. Body weight, high
      animal protein intake, family stressors (e.g., single parenting), and physical
      activity seem to influence AAM in most populations. CONCLUSIONS: The data about
      influence of nongenetic factors on AAM are still inconsistent. The factors
      affecting prenatal and early childhood growth seem to have a larger effect on
      further sexual maturation. Further studies are needed in order to validate the
      association between other environmental determinants and AAM in different
      ethnical groups.

PMID- 25050347
TI  - Platelet-rich plasma in bone regeneration: engineering the delivery for improved
      clinical efficacy.
AB  - Human bone is a tissue with a fairly remarkable inherent capacity for
      regeneration; however, this regenerative capacity has its limitations, and
      defects larger than a critical size lack the ability to spontaneously heal. As
      such, the development and clinical translation of effective bone regeneration
      modalities are paramount. One regenerative medicine approach that is beginning to
      gain momentum in the clinical setting is the use of platelet-rich plasma (PRP).
      PRP therapy is essentially a method for concentrating platelets and their
      intrinsic growth factors to stimulate and accelerate a healing response. While
      PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its
      use and delivery have not been optimized for bone regeneration. Issues remain
      with the effective delivery of the platelet-derived growth factors to a localized
      site of injury, the activation and temporal release of the growth factors, and
      the rate of growth factor clearance. This review will briefly describe the
      physiological principles behind PRP use and then discuss how engineering its
      method of delivery may ultimately impact its ability to successfully translate to
      widespread clinical use. 

PMID- 25050348
TI  - Survey on knowledge, attitudes, and training needs of Italian residents on
      genetic tests for hereditary breast and colorectal cancer.
AB  - OBJECTIVES: The aim of the study was to assess knowledge and attitudes of medical
      residents working in Universita Cattolica del Sacro Cuore, Rome, Italy, on
      genetic tests for breast and colorectal cancer. METHODS: We distributed self
      administered questionnaire to the residents. Logistic regression models were used
      to evaluate the determinants of knowledge and attitudes towards the tests.
      RESULTS: Of 754 residents, 364 filled in questionnaire. Around 70% and 20%
      answered correctly >80% of questions on breast and colorectal cancer tests,
      respectively. Knowledge on tests for breast cancer was higher among residents who
      attended course on cancer genetic testing during graduate training (odds ratio
      (OR): 1.72; 95% confidence interval (CI): 1.05-2.82) and inversely associated
      with male gender (OR: 0.55; 95% CI: 0.35-0.87). As for colorectal cancer,
      residents were more knowledgeable if they attended courses on cancer genetic
      testing (OR: 2.08; 95% CI: 1.07-4.03) or postgraduate training courses in
      epidemiology and evidence-based medicine (OR: 1.95; 95% CI: 1.03-3.69). More than
      70% asked for the additional training on the genetic tests for cancer during the
      specialization school. CONCLUSION: The knowledge of Italian residents on genetic
      tests for colorectal cancer appears to be insufficient. There is a need for
      additional training in this field.

PMID- 25050349
TI  - Exercise training, lymphocyte subsets and their cytokines production: experience
      of an Italian professional football team and their impact on allergy.
AB  - BACKGROUND: In recent years, numerous articles have attempted to shed light on
      our understanding of the pathophysiological mechanisms of exercise-induced
      immunologic changes and their impact on allergy and asthma. It is known that
      lymphocyte subclasses, cytokines, and chemokines show modifications after
      exercise, but outcomes can be affected by the type of exercise as well as by its
      intensity and duration. Interesting data have been presented in many recent
      studies on mouse models, but few studies on humans have been performed to check
      the long-term effects of exercise over a whole championship season. METHODS: This
      study evaluated lymphocyte subsets and their intracellular IL-2, IL-4, TNF-alpha,
      and IFN-gamma production in professional football (soccer) players, at three
      stages of the season, to evaluate if alterations occur, particularly in relation
      to their allergic status. RESULTS AND CONCLUSION: Despite significant mid-season
      alterations, no significant lymphocyte subclasses count modifications, except for
      NKs that were significantly higher, were observed at the end. IL-2 and IL-4
      producing cells showed a significant decrease (P = 0.018 and P = 0.001, but in a
      steady fashion for IL-4), confirming the murine data about the potential
      beneficial effects of aerobic exercise for allergic asthma.

PMID- 25050350
TI  - Biomarkers as predictors of recurrence following curative resection for
      pancreatic ductal adenocarcinoma: a review.
AB  - Pancreatic ductal adenocarcinoma (PDA) is the fourth most common cancer causing
      death in the United States. Early tumor recurrence is an important contributor to
      the dismal prognosis. The availability of an accurate prognostic biomarker for
      predicting disease recurrence following curative resection will be beneficial for
      patient care. Most of the currently studied biomarkers remain in the
      investigational phase, with CA 19-9 being the only biomarker currently approved
      by the FDA. Herein, we review the utility of CA 19-9 and other investigational
      cellular, gene, and molecular tumor markers for predicting PDA recurrence
      following curative surgical resection. 

PMID- 25050351
TI  - MR imaging findings in alcoholic and nonalcoholic acute Wernicke's
      encephalopathy: a review.
AB  - Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by
      thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset
      of mental status changes, ocular abnormalities, and ataxia. Apart from chronic
      alcoholism, the most common cause of WE, a lot of other conditions causing
      malnutrition and decreasing thiamine absorption such as gastrointestinal surgical
      procedures and hyperemesis gravidarum must be considered as predisposing factors.
      Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed,
      leading to persistent dysfunctions and, in some cases, to death. Nowadays, MR
      imaging of the brain, showing T2 and FLAIR hyperintensities in typical (thalami,
      mammillary bodies, tectal plate, and periaqueductal area) and atypical areas
      (cerebellum, cranial nerve nuclei, and cerebral cortex), is surely the most
      important and effective tool in the diagnostic assessment of WE. The aim of this
      paper is to propose a state of the art of the role of MR imaging in the early
      diagnosis of this complex disease. 

PMID- 25050353
TI  - Enhanced analgesic properties and reduced ulcerogenic effect of a mononuclear
      copper(II) complex with fenoprofen in comparison to the parent drug: promising
      insights in the treatment of chronic inflammatory diseases.
AB  - Analgesic and ulcerogenic properties have been studied for the copper(II)
      coordination complex of the nonsteroidal anti-inflammatory drug Fenoprofen and
      imidazole [Cu(fen)2(im)2] (Cu: copper(II) ion; fen: fenoprofenate anion from
      Fenoprofen, im: imidazole). A therapeutic dose of 28 mg/kg was tested for
      [Cu(fen)2(im)2] and 21 mg/kg was employed for Fenoprofen calcium, administered by
      oral gavage in female mice to compare the therapeutic properties of the new
      entity. The acetic acid induced writhing test was employed to study visceral
      pain. The percentage of inhibition in writhing and stretching was 78.9% and 46.2%
      for the [Cu(fen)2(im)2] and Fenoprofen calcium, respectively. This result
      indicates that the complex could be more effective in diminishing visceral pain.
      The formalin test was evaluated to study the impact of the drugs over nociceptive
      and inflammatory pain. The complex is a more potent analgesic on inflammatory
      pain than the parent drug. Ulcerogenic effects were evaluated using a model of
      gastric lesions induced by hypothermic-restraint stress. Fenoprofen calcium salt
      caused an ulcer index of about 79 mm(2) while the one caused by [Cu(fen)2(im)2]
      was 22 mm(2). The complex diminished the development of gastric mucosal ulcers in
      comparison to the uncomplexed drug. Possible mechanisms of action related to both
      therapeutic properties have been discussed.

PMID- 25050352
TI  - Antibodies in the pathogenesis of hypertension.
AB  - It has long been known that circulating levels of IgG and IgM antibodies are
      elevated in patients with essential and pregnancy-related hypertension. Recent
      studies indicate these antibodies target, and in many cases activate, G-protein
      coupled receptors and ion channels. Prominent among these protein targets are AT1
      receptors, alpha1-adrenoceptors, beta1-adrenoceptors, and L-type voltage operated
      Ca(2+) channels, all of which are known to play key roles in the regulation of
      blood pressure through modulation of vascular tone, cardiac output, and/or
      Na(+)/water reabsorption in the kidneys. This suggests that elevated antibody
      production may be a causal mechanism in at least some cases of hypertension. In
      this brief review, we will further describe the protein targets of the antibodies
      that are elevated in individuals with essential and pregnancy-related
      hypertension and the likely pathophysiological consequences of antibody binding
      to these targets. We will speculate on the potential mechanisms that underlie
      elevated antibody levels in hypertensive individuals and, finally, we will
      outline the therapeutic opportunities that could arise with a better
      understanding of how and why antibodies are produced in hypertension.

PMID- 25050354
TI  - Correlation between density and resorption of fresh-frozen and autogenous bone
      grafts.
AB  - TRIAL DESIGN: This analysis compared the outcome of fresh-frozen versus
      autologous bone block grafts for horizontal ridge augmentation in patients with
      Cawood and Howell class IV atrophies. METHODS: Seventeen patients received
      autologous grafts and 21 patients received fresh-frozen bone grafts. Patients
      underwent CT scans 1 week and 6 months after surgery for graft volume and density
      analysis. RESULTS: Two autologous and 3 fresh-frozen grafts failed. Autologous
      and fresh-frozen grafts lost, respectively, 28% and 46% of their initial volume
      (P = 0.028). It is noteworthy that less dense fresh-frozen blocks lost more
      volume than denser grafts (61% versus 16%). CONCLUSIONS: According to these 6
      month results, only denser fresh-frozen bone graft may be an acceptable
      alternative to autologous bone for horizontal ridge augmentation. Further studies
      are needed to investigate its behaviour at longer time points.

PMID- 25050355
TI  - Isolation, screening, and identification of cellulolytic bacteria from natural
      reserves in the subtropical region of China and optimization of cellulase
      production by Paenibacillus terrae ME27-1.
AB  - From different natural reserves in the subtropical region of China, a total of
      245 aerobic bacterial strains were isolated on agar plates containing sugarcane
      bagasse pulp as the sole carbon source. Of the 245 strains, 22 showed hydrolyzing
      zones on agar plates containing carboxymethyl cellulose after Congo-red staining.
      Molecular identification showed that the 22 strains belonged to 10 different
      genera, with the Burkholderia genus exhibiting the highest strain diversity and
      accounting for 36.36% of all the 22 strains. Three isolates among the 22 strains
      showed higher carboxymethyl cellulase (CMCase) activity, and isolate ME27-1
      exhibited the highest CMCase activity in liquid culture. The strain ME27-1 was
      identified as Paenibacillus terrae on the basis of 16S rRNA gene sequence
      analysis as well as physiological and biochemical properties. The optimum pH and
      temperature for CMCase activity produced by the strain ME27-1 were 5.5 and 50 
      degrees C, respectively, and the enzyme was stable at a wide pH range of 5.0-9.5.
      A 12-fold improvement in the CMCase activity (2.08 U/mL) of ME27-1 was obtained
      under optimal conditions for CMCase production. Thus, this study provided further
      information about the diversity of cellulose-degrading bacteria in the
      subtropical region of China and found P. terrae ME27-1 to be highly cellulolytic.

PMID- 25050356
TI  - Acute superoxide radical scavenging reduces blood pressure but does not influence
      kidney function in hypertensive rats with postischemic kidney injury.
AB  - Acute kidney injury (AKI) is associated with significant morbidity and mortality
      in hypertensive surroundings. We investigated superoxide radical molecules
      influence on systemic haemodynamic and kidney function in spontaneously
      hypertensive rats (SHR) with induced postischemic AKI. Experiment was performed
      in anesthetized adult male SHR. The right kidney was removed, and left renal
      artery was subjected to ischemia by clamping for 40 minutes. The treated group
      received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5
      minutes before, during, and 175 minutes after the period of reperfusion, while
      the control AKI group received the vehicle via the same route. All parameters
      were measured 24 h after renal reperfusion. TEMPOL treatment significantly
      decreased mean arterial pressure and total peripheral resistance (P < 0.05)
      compared to AKI control. It also increased cardiac output and catalase activity
      (P < 0.05). Lipid peroxidation and renal vascular resistance were decreased in
      TEMPOL (P < 0.05). Plasma creatinine and kidney morphological parameters were
      unchanged among TEMPOL treated and control groups. Our study shows that
      superoxide radicals participate in haemodynamic control, but acute superoxide
      scavenging is ineffective in glomerular and tubular improvement, probably due to
      hypertension-induced strong endothelial dysfunction which neutralizes beneficial
      effects of O2(-) scavenging.

PMID- 25050357
TI  - Seropositivity and coinfection of hepatitis B and C among patients seeking
      hospital care in Islamabad, Pakistan.
AB  - The undertaken study was conducted to find out the seroprevalence and coinfection
      of HBV and HCV infection among patients seeking hospital care. A total of 845
      samples were received at tertiary care hospital of Islamabad and were screened
      for hepatitis B and C. The ELISA was used to detect antigen for HBV and
      antibodies for HCV in patient serum. Among 845 collected samples, 255 (30.1%)
      were seropositive for HBV and HCV. Out of 255 seropositive samples, 45 (5.3%)
      were positive for HBsAg while 199 (23.5%) were positive for anti-HCV. Among 255,
      11 (1.3%) were seropositive for both HBsAg and anti-HCV (coinfection). Among the
      seropositive male, HBV was more prevalent (23.8%) while female patients had a
      high incidence of HCV (52.2%). Among the age group variable, HBV, HCV, and
      coinfection were found to be more common in the age groups of 21-30 (29%) and 30
      40 (24%) years. The seropositivity for HBsAg was higher in unmarried individuals
      (31.2%) while anti-HCV was more prevalent in married individuals (84%). The
      present study provides the preliminary information about high HCV and HBV
      prevalence. Findings from the current study will be helpful for the better
      management and control of viral hepatitis among patients seeking hospital care. 

PMID- 25050358
TI  - Receptors of hypothalamic-pituitary-ovarian-axis hormone in uterine myomas.
AB  - In this study the expression of GnRH, FSH, LH, ER-alpha, ER-beta, and PR
      receptors was examined in uterine myomas of women in reproductive and
      perimenopausal age. In cases of GnRH and tropic hormones a membranous and
      cytoplasmic immunohistochemical reaction was detected, in cases of ER-alpha and
      PR the reaction was located in cell nucleus, and in the case of ER-beta it
      manifested also a cytoplasmic location. In some of the examined cases the
      expression was detected in endometrium, myocytes, and endothelium of blood
      vessels, in uterine glands and myoma cells. In myometrium the level of GnRH and
      LH receptors increases with age, whereas the level of progesterone and both
      estrogen receptors decreases. In myomas of women in reproductive age,
      independently of their size, expression of GnRH, FSH, and LH receptors was more
      pronounced than in myometrium. In women of perimenopausal age, independently of
      myoma size, expression of LH and estrogen alpha receptors was higher while
      expression of GnRH receptors was lower than in myometrium. FSH receptor
      expression was not observed. Expression of estrogen receptor beta was not
      affected by age of the woman or size of myoma. Analysis of obtained results
      indicates on existing in small myomas local feedback axis between GnRH-LH
      progesterone. 

PMID- 25050359
TI  - Nucleic acid aptamers: research tools in disease diagnostics and therapeutics.
AB  - Aptamers are short sequences of nucleic acid (DNA or RNA) or peptide molecules
      which adopt a conformation and bind cognate ligands with high affinity and
      specificity in a manner akin to antibody-antigen interactions. It has been
      globally acknowledged that aptamers promise a plethora of diagnostic and
      therapeutic applications. Although use of nucleic acid aptamers as targeted
      therapeutics or mediators of targeted drug delivery is a relatively new avenue of
      research, one aptamer-based drug "Macugen" is FDA approved and a series of
      aptamer-based drugs are in clinical pipelines. The present review discusses the
      aspects of design, unique properties, applications, and development of different
      aptamers to aid in cancer diagnosis, prevention, and/or treatment under defined
      conditions. 

PMID- 25050362
TI  - The current status of usability studies of information technologies in China: a
      systematic study.
AB  - OBJECTIVES: To systematically review and analyze the current status and
      characteristics of usability studies in China in the field of information
      technology in general and in the field of healthcare in particular. METHODS: We
      performed a quantitative literature analysis in three major Chinese academic
      databases and one English language database using Chinese search terms equivalent
      to the concept of usability. RESULTS: Six hundred forty-seven publications were
      selected for analysis. We found that in China the literature on usability in the
      field of information technology began in 1994 and increased thereafter. The
      usability definitions from ISO 9241-11:1998 and Nielsen (1993) have been widely
      recognized and cited. Authors who have published several publications are rare.
      Fourteen journals have a publishing rate over 1%. Only nine publications about
      HIT were identified. DISCUSSIONS: China's usability research started relatively
      late. There is a lack of organized research teams and dedicated usability
      journals. High-impact theoretical studies are scarce. On the application side, no
      original and systematic research frameworks have been developed. The
      understanding and definition of usability is not well synchronized with
      international norms. Besides, usability research in HIT is rare. CONCLUSIONS:
      More human and material resources need to be invested in China's usability
      research, particularly in HIT.

PMID- 25050361
TI  - Antiangiogenesis therapy of endometriosis using PAMAM as a gene vector in a
      noninvasive animal model.
AB  - OBJECTIVE: To evaluate the characteristics and antiangiogenic effects of
      endostatin-loaded PAMAM on endometriosis in a noninvasive animal model. MATERIALS
      AND METHODS: A noninvasive animal model was established by injecting adenovirus
      GFP transfected endometrial stromal and glandular epithelial cells subcutaneously
      into nude mice. Endostatin-loaded PAMAM was prepared and identified by
      transmission electron microscopy. For in vitro studies, the DNA protection and
      cytotoxicity of PAMAM were investigated and compared with Lipofectamine 2000. For
      in vivo study, endostatin-loaded PAMAM was injected into the noninvasive model
      and evaluated by continuously observing the fluorescent lesion, lesion weight,
      microvessel density and VEGF immunostaining. RESULTS: Compared with Lipofectamine
      2000, PAMAM and HC PAMAM-ES group, MC PAMAM-ES group and LC PAMAM-ES group
      demonstrated a better stromal cells protective such that MC PAMAM-ES group of
      CCK8 was 0.617 +/- 0.122 at 24 hr and 0.668 +/- 0.143 at 48 hr and LC PAMAM-ES
      group of CCK8 was 0.499 +/- 0.103 at 24 hr and 0.610 +/- 0.080 at 48 hr in
      stromal cells (P < 0.05) but similar cytotoxicity in glandular epithelial cells
      in vitro. After 16 hrs of digestion, DNA decreased slightly under the protection
      of PAMAM. Endostatin-loaded PAMAM of HD PAMAM-ES group and LD PAMAM-ES group
      inhibited the growth of the endometriotic lesion in vivo at days 15, 20, 25 and
      30 detected by noninvasive observation after injecting one dose endostatin of
      various medicines into the endometrial lesion in each mouse on day 10 (P < 0.05)
      and confirmed by lesion weight at day 30 with HD PAMAM-ES group being 0.0104 +/-
      0.0077 g and LD PAMAM-ES group being 0.0140 +/- 0.0097 g (P < 0.05).
      Immunohistochemistry results showed that endostatin-loaded PAMAM reduced the
      microvessel density 3.8 +/- 2.4 especially in HD PAMAM-ES group in the lesion (P
      < 0.05). CONCLUSION: Endostatin-loaded PAMAM inhibits the development of
      endometriosis through an antiangiogenic mechanism and can be observed through the
      noninvasive endometriosis model.

PMID- 25050360
TI  - Chronic dietary supplementation of 4% figs on the modification of oxidative
      stress in Alzheimer's disease transgenic mouse model.
AB  - We assessed the changes in the plasma Abeta, oxidative stress/antioxidants, and
      membrane bound enzymes in the cerebral cortex and hippocampus of Alzheimer's
      disease (AD) transgenic mice (Tg2576) after dietary supplementation of Omani figs
      fruits for 15 months along with spatial memory and learning test. AD Tg mice on
      control diet without figs showed significant impairment in spatial learning
      ability compared to the wild-type mice on same diet and figs fed Tg mice as well.
      Significant increase in oxidative stress and reduced antioxidant status were
      observed in AD Tg mice. 4% figs treated AD Tg mice significantly attenuated
      oxidative damage, as evident by decreased lipid peroxidation and protein
      carbonyls and restoration of antioxidant status. Altered activities of membrane
      bound enzymes (Na(+) K(+) ATPase and acetylcholinesterase (AChE)) in AD Tg mice
      brain regions and was restored by figs treatment. Further, figs supplementation
      might be able to decrease the plasma levels of Abeta (1-40, 1-42) significantly
      in Tg mice suggesting a putative delay in the formation of plaques, which might
      be due to the presence of high natural antioxidants in figs. But this study
      warrants further extensive investigation to find a novel lead for a therapeutic
      target for AD from figs. 

PMID- 25050363
TI  - Correlation between TMD and cervical spine pain and mobility: is the whole body
      balance TMJ related?
AB  - Temporomandibular dysfunction (TMD) is considered to be associated with imbalance
      of the whole body. This study aimed to evaluate the influence of TMD therapy on
      cervical spine range of movement (ROM) and reduction of spinal pain. The study
      group consisted of 60 patients with TMD, cervical spine pain, and limited
      cervical spine range of movements. Subjects were interviewed by a questionnaire
      about symptoms of TMD and neck pain and had also masticatory motor system
      physically examined (according to RDC-TMD) and analysed by JMA ultrasound device.
      The cervical spine motion was analysed using an MCS device. Subjects were
      randomly admitted to two groups, treated and control. Patients from the treated
      group were treated with an occlusal splint. Patients from control group were
      ordered to self-control parafunctional habits. Subsequent examinations were
      planned in both groups 3 weeks and 3 months after treatment was introduced. The
      results of tests performed 3 months after the beginning of occlusal splint
      therapy showed a significant improvement in TMJ function (P > 0.05), cervical
      spine ROM, and a reduction of spinal pain. The conclusion is that there is a
      significant association between TMD treatment and reduction of cervical spine
      pain, as far as improvement of cervical spine mobility. 

PMID- 25050364
TI  - Neuropeptide substance P improves osteoblastic and angiogenic differentiation
      capacity of bone marrow stem cells in vitro.
AB  - Our previous work showed that implanting a sensory nerve or vascular bundle when
      constructing vascularized and neurotized bone could promote bone osteogenesis in
      tissue engineering. This phenomenon could be explained by the regulatory function
      of neuropeptides. Neuropeptide substance P (SP) has been demonstrated to
      contribute to bone growth by stimulating the proliferation and differentiation of
      bone marrow stem cells (BMSCs). However, there have been no prior studies on the
      association between Wnt signaling and the mechanism of SP in the context of BMSC
      differentiation. Our results have shown that SP could enhance the differentiation
      of BMSCs by activating gene and protein expression via the Wnt pathway and by
      translocating beta-catenin, which can be inhibited by Wnt signaling blocker
      treatment or by the NK-1 antagonist. SP could also increase the growth factor
      level of bone morphogenetic protein-2 (BMP-2). Additionally, SP could enhance the
      migration ability of BMSCs, and the promotion of vascular endothelial growth
      factor (VEGF) expression by SP has been studied. In conclusion, SP could induce
      osteoblastic differentiation via the Wnt pathway and promote the angiogenic
      ability of BMSCs. These results indicate that a vascularized and neurotized
      tissue-engineered construct could be feasible for use in bone tissue engineering
      strategies. 

PMID- 25050365
TI  - Right heart functional changes in the acute, hypercapnic exacerbations of COPD.
AB  - OBJECTIVE: To investigate the correlation between respiratory failure and the
      pulmonary circulation. We focused on anatomical and functional changes of the
      right heart. Design. Clinical investigation. METHODS: We evaluated 75 patients
      hospitalized in our respiratory ward for COPD exacerbation. All patients
      underwent transthoracic echocardiography and measurements of right heart
      chambers. Moreover all patients underwent blood tests, measurement of blood
      pressure, evaluation of body mass index (BMI), ECGs, pulmonary function tests,
      and the Saint George's Respiratory Questionnaire (SGRQ). RESULTS: Among 75
      patients consecutively hospitalized, 56 patients with a COPD exacerbation were
      included in our study. We have emphasized the higher value of PAPs and the
      increased size of right atrial area in severe COPD patients. Significant
      correlation was observed between low values of PaO2 and larger area of the right
      atrium. The measurement of TAPSE showed a right ventricular dysfunction in all
      patients but especially in severe COPD patients. We have obtained a significant
      correlation between TAPSE and arterial blood gas. CONCLUSIONS: In patients with
      chronic respiratory failure, blood gas parameters should be considered as
      negative prognostic factors of right heart failure. Respiratory failure shows a
      relationship with pulmonary hypertension and with the anatomy and function of the
      right heart sections.

PMID- 25050366
TI  - Anticancer and antioxidant activity of bread enriched with broccoli sprouts.
AB  - This study is focused on antioxidant and anticancer capacity of bread enriched
      with broccoli sprouts (BS) in the light of their potential bioaccessibility and
      bioavailability. Generally, bread supplementation elevated antioxidant potential
      of product (both nonenzymatic and enzymatic antioxidant capacities); however, the
      increase was not correlated with the percent of BS. A replacement up to 2% of BS
      gives satisfactory overall consumers acceptability and desirable elevation of
      antioxidant potential. High activity was especially found for extracts obtained
      after simulated digestion, which allows assuming their protective effect for
      upper gastrointestinal tract; thus, the anticancer activity against human stomach
      cancer cells (AGS) was evaluated. A prominent cytostatic response paralleled by
      the inhibition of AGS motility in the presence of potentially mastication
      extractable phytochemicals indicates that phenolic compounds of BS retain their
      biological activity in bread. Importantly, the efficient phenolics concentration
      was about 12 MUM for buffer extract, 13 MUM for extracts after digestion in
      vitro, and 7 MUM for extract after absorption in vitro. Our data confirm
      chemopreventive potential of bread enriched with BS and indicate that BS comprise
      valuable food supplement for stomach cancer chemoprevention.

PMID- 25050367
TI  - The outcomes of primary scleral buckling during repair of posterior segment open
      globe injuries.
AB  - OBJECTIVE: To compare visual outcomes of eyes which underwent primary scleral
      buckling (PSB) treatment during posterior segment open-globe injury (OGI) repair
      with eyes not treated with PSB. METHODS: We retrospectively reviewed 38 eyes
      which underwent a posterior segment OGI repair with no preoperative evidence of
      retinal detachment (RD) at Soroka University Medical Center (1995-2010). 19 (50%)
      underwent scleral repair alone (control group) and the other 19 eyes were treated
      with PSB also (PSB group). We compared visual outcomes in these two groups and
      rates of subsequent postoperative complications. RESULTS: Baseline
      characteristics of the groups were similar. Compared with the control group, the
      PSB group had statistically significant lower rates of proliferative
      vitreoretinopathy (PVR) (5.3% versus 38.4%, P < 0.05) and a trend towards lower
      rates of RD (15.8% versus 41.1%, P = 0.1). PSB group eyes had a statistically
      significant improvement of their best distance visual acuity (BDVA) with lower
      means of final BDVA-grade (P < 0.05) and logMAR vision (P < 0.05). Eyes in the
      control group had no improvement in these parameters. CONCLUSION: PSB procedure
      during posterior segment OGI repair may decrease the risk of subsequent retinal
      complications and improve final visual outcome.

PMID- 25050368
TI  - Corneal collagen cross-linking with and without epithelial removal: a
      contralateral study with 0.5% hypotonic riboflavin solution.
AB  - PURPOSE: Our main purpose was to compare safety and efficacy in the treatment of
      progressive keratoconus with "epithelium-on" and "epithelium-off" corneal
      collagen cross-linking (CXL). Our secondary purpose was to evaluate efficacy of
      CXL when hypotonic 0.5% riboflavin is used as photosensitizer. METHODS: One eye
      of 20 patients with bilateral progressive keratoconus was randomly treated for
      "epithelium-on" CXL (group 1) while the fellow eye underwent "epithelium-off" CXL
      (group 2). Hypotonic 0.5% riboflavin was used in both groups. Visual acuity,
      refraction, corneal topography, and wavefront aberrometry were evaluated at
      baseline and after 1, 6, and 12 months. Specular microscopy was performed on 10
      patients preoperatively and after 12 months. Postoperative pain was evaluated
      using a patient questionnaire. RESULTS: Uncorrected and corrected distance visual
      acuity improved significantly in both groups. Refraction, topography, and
      aberrometry showed nonsignificant changes from the preoperative status throughout
      the 12-month follow-up in both groups. Moreover, the outcomes between the groups
      were comparable at all follow-up points. Endothelial cell-count was stable.
      Postoperative pain length was shorter in group 1 (P < 0.001). CONCLUSION:
      "Epithelium-on" and "epithelium-off" CXL using hypotonic 0.5% riboflavin were
      equally safe and effective in stabilization of keratoconus. Topography and
      aberrometry outcomes in both groups failed to show any significant improvements.
      This study is registered at ClinicalTrials.gov: NCT01181219.

PMID- 25050369
TI  - The inhibition of folylpolyglutamate synthetase (folC) in the prevention of drug
      resistance in Mycobacterium tuberculosis by traditional Chinese medicine.
AB  - Tuberculosis (TB) is an infectious disease caused by many strains of
      mycobacteria, but commonly Mycobacterium tuberculosis. As a possible method of
      reducing the drug resistance of M. tuberculosis, this research investigates the
      inhibition of Folylpolyglutamate synthetase, a protein transcript from the
      resistance association gene folC. After molecular docking to screen the
      traditional Chinese medicine (TCM) database, the candidate TCM compounds, with
      Folylpolyglutamate synthetase, were selected by molecular dynamics. The 10,000 ps
      simulation in association with RMSD analysis and total energy and structural
      variation defined the protein-ligand interaction. The selected TCM compounds
      Saussureamine C, methyl 3-O-feruloylquinate, and Labiatic acid have been found to
      inhibit the activity of bacteria and viruses and to regulate immunity. We also
      suggest the possible pathway in protein for each ligand. Compared with the
      control, similar interactions and structural variations indicate that these
      compounds might have an effect on Folylpolyglutamate synthetase. Finally, we
      suggest Saussureamine C is the best candidate compound as the complex has a high
      score, maintains its structural composition, and has a larger variation value
      than the control, thus inhibiting the drug resistance ability of Mycobacterium
      tuberculosis.

PMID- 25050370
TI  - Immunopathological aspects of experimental Trypanosoma cruzi reinfections.
AB  - Chagas disease is caused by Trypanosoma cruzi infection. Besides the host-related
      factors, such as immune response and genetic background, the parasite, strain,
      and occurrences of reinfection episodes, may influence disease outcome. Our
      results demonstrate that both the primary infection and the reinfection with the
      Colombiana strain are connected with lower survival rate of the mice. After
      reinfection, parasitaemia is approximately ten times lower than in primary
      infected animals. Only Colombiana, Colombiana/Colombiana, and Y/Colombiana groups
      presented amastigote nests in cardiac tissue. Moreover, the mice infected and/or
      reinfected with the Colombiana strain had more T. cruzi nests, more intense
      inflammatory infiltrate, and higher in situ expression of TNF-alpha and IFN-gamma
      than Y strain. Antigen-stimulated spleen cells from infected and/or reinfected
      animals produced higher levels of TNF-alpha, IFN-gamma, and IL-10. Our results
      reinforce the idea that Chagas disease outcome is influenced by the strain of the
      infective parasite, being differentially modulated during reinfection episodes.
      It highlights the need of control strategies involving parasite strain
      characterization in endemic areas for Chagas disease. 

PMID- 25050371
TI  - Inhibitory potential of Turbinaria ornata against key metabolic enzymes linked to
      diabetes.
AB  - One of the therapeutic approaches in treating diabetes is to reduce postprandial
      hyperglycemia by inhibiting major carbohydrate hydrolyzing enzymes. In the
      present study, crude extracts of marine seaweed, Turbinaria ornata, were tested
      for their antidiabetic potential using enzyme inhibitory assays (alpha-amylase,
      alpha-glucosidase, and dipeptidyl peptidase-IV). Among the tested extracts,
      methanol and acetone extracts showed significant inhibitory effects on alpha
      amylase (IC50 250.9 MUg/mL), alpha-glucosidase (535.6 MUg/mL), and dipeptidyl
      peptidase-4 (55.2 MUg/mL), respectively. Free radical scavenging activity of
      these extracts was analyzed using DPPH assay (65%). Extracts were tested for in
      vitro toxicity using DNA fragmentation assay, haemolytic assay, and MTT assay.
      None of the extracts showed toxicity in tested models. Furthermore, GC-MS
      analysis of lead extracts showed the presence of major compounds, hentriacontane,
      z, z-6, 28-heptatriactontadien-2-one, 8-heptadecene, and 1-heptacosanol. Our
      findings suggest that Turbinaria ornata can be used as a potential source for
      further in vivo studies in controlling hyperglycemia.

PMID- 25050372
TI  - Intraoperative assessment of surgical margins of oral squamous cell carcinoma
      using frozen sections: a practical clinicopathological management for
      recurrences.
AB  - BACKGROUND: Local recurrence remains a challenging clinical issue for the
      treatment of oral squamous cell carcinoma (SCC). We analyzed retrospectively how
      effective the frozen section technique (FS) was against recurrences of oral SCC.
      METHODS: We screened 343 surgical samples from 236 patients who had oral SCC,
      carcinoma in situ (CIS), or epithelial dysplasia, and we followed up their
      clinical outcomes for at least 5 years. Histopathological states of surgical
      margins were compared between FS and surgical materials in relapse and relapse
      free groups, respectively. RESULTS: Among the 236 patients, 191 were classified
      into the relapse-free group, and 45 into the relapse group. FS was more
      frequently performed in the relapse-free group (128/191) than in the relapse
      group (83/152). Histopathologically, moderate dysplasia or CIS (borderline
      malignancies) and SCC were recognized in 55 samples of the relapse-free group and
      in 57 of the relapse group. For those surgical margins with borderline
      malignancies, additional incisions were performed in 38 of the 55 relapse-free
      cases, which reduced to 20 from the 38 margins with borderline malignancies
      (47.4% reduction), and in 39 of the 57 relapse cases, which reduced to only 3 of
      39 (7.7% reduction). CONCLUSIONS: The intraoperative assessment of surgical
      margins by FS is essential in preventing recurrences of oral mucosal
      malignancies.

PMID- 25050373
TI  - Incidence of otolaryngological symptoms in patients with temporomandibular joint
      dysfunctions.
AB  - The functional disorders of the masticatory organ are the third stomatological
      disease to be considered a populational disease due to its chronicity and
      widespread prevalence. Otolaryngological symptoms are a less common group of
      dysfunction symptoms, including sudden hearing impairment or loss, ear plugging
      sensation and earache, sore and burning throat, difficulties in swallowing,
      tinnitus, and vertigo. The diagnostic and therapeutic problems encountered in
      patients with the functional disorders of the masticatory organ triggered our
      interest in conducting retrospective studies with the objective of assessing the
      incidence of otolaryngological symptoms in patients subjected to prosthetic
      treatment of the functional disorders of masticatory organ on the basis of the
      analysis of medical documentation containing data collected in medical
      interviews. MATERIAL AND METHODS: Retrospective study was conducted by analyzing
      the results of medical interviews of 1208 patients, who had reported for
      prosthetic treatment at the Functional Disorders Clinic of the Department of
      Dental Prosthetics of Jagiellonian University Medical College in Cracow between
      2008 and March 14, 2014. RESULTS: Otolaryngological symptoms were observed in 141
      patients. The most common symptoms in the study group were earache and sudden
      hearing impairment; no cases of sudden hearing loss were experienced.

PMID- 25050374
TI  - The impact of arthroscopic capsular release in patients with primary frozen
      shoulder on shoulder muscular strength.
AB  - The aim of this study was to evaluate the impact of arthroscopic capsular release
      in patients with primary frozen shoulder on muscular strength of nonaffected and
      treated shoulder after at least two-year follow-up after the surgery. The
      assessment included twenty-seven patients, who underwent arthroscopic capsular
      release due to persistent limitation of range of passive and active motion,
      shoulder pain, and limited function of upper limb despite 6-month conservative
      treatment. All the patients underwent arthroscopic superior, anteroinferior, and
      posterior capsular release. After at least two-year follow-up, measurement of
      muscular strength of abductors, flexors, and external and internal rotators of
      the operated and nonaffected shoulder, as well as determination of range of
      motion (ROM) and function (ASES) in the operated and nonaffected shoulder, was
      performed. Measurement of muscular strength in the patient group did not reveal
      statistically significant differences between operated and nonaffected shoulder.
      The arthroscopic capsular release does not have significant impact on the
      decrease in the muscular strength of the operated shoulder. 

PMID- 25050376
TI  - Development and characterization of in situ oral gel of spiramycin.
AB  - The present investigation deals with the optimization, formulation, and
      characterization of oral in situ gel of spiramycin. Sodium alginate and
      hydroxypropyl methylcellulose were used as cross-linking and viscosifying agents,
      respectively. Sodium bicarbonate was used as a floating agent. In preformulation
      studies, the melting point, pH, and partition coefficient were found to be 133 
      degrees C, 9.5, and 0.193, respectively. The drug had retention time at around
      2.65 minutes in high performance liquid chromatography (HPLC). During
      compatibility studies of drug with all polymers, we observed that there were no
      changes in the FTIR spectra of a mixture of drug and polymers. All the
      formulations showed good pourability. Floating time and total floating time were
      ~30 sec and >12 hours, respectively. During in vitro drug release studies, the
      drug was released from the formulation around 80-100% for 12-16 hrs. In TEM
      analysis, we found that the drug molecules were well entrapped in the polymer and
      the drug was released slowly for up to 12 hrs. In these studies, we found that
      the concentration of sodium alginate and HPMC had significant influence on
      floating lag time, gelling capacity, and cumulative percentage drug release.
      During antimicrobial studies, we found that the formulation containing spiramycin
      showed good zone of inhibition against different microbial strains
      (Staphylococcus aureus and Escherichia coli).

PMID- 25050375
TI  - Biological width around one- and two-piece implants retrieved from human jaws.
AB  - Several histologic studies regarding peri-implant soft tissues and biological
      width around dental implants have been done in animals. However, these findings
      in human peri-implant soft tissues are very scarce. Therefore, the aim of this
      case series was to compare the biological width around unloaded one- and two
      piece implants retrieved from human jaws. Eight partially edentulous patients
      received 2 test implants in the posterior mandible: one-piece (solid implants
      that comprise implant and abutment in one piece) and two-piece (external hexagon
      with a healing abutment) implants. After 4 months of healing, the implants and
      surrounding tissue were removed for histologic analysis. The retrieved implants
      showed healthy peri-implant bone and exhibited early stages of maturation.
      Marginal bone loss, gaps, and fibrous tissue were not present around retrieved
      specimens. The biologic width dimension ranged between 2.55 +/- 0.16 and 3.26 +/-
      0.15 to one- and two-piece implants, respectively (P < 0.05). This difference was
      influenced by the connective tissue attachment, while sulcus depth and epithelial
      junction presented the same dimension for both groups (P > 0.05). Within the
      limits of this study, it could be shown that two-piece implants resulted in the
      thickening of the connective tissue attachment, resulting in the increase of the
      biological width, when compared to one-piece implants. 

PMID- 25050377
TI  - A graphic method for identification of novel glioma related genes.
AB  - Glioma, as the most common and lethal intracranial tumor, is a serious disease
      that causes many deaths every year. Good comprehension of the mechanism
      underlying this disease is very helpful to design effective treatments. However,
      up to now, the knowledge of this disease is still limited. It is an important
      step to understand the mechanism underlying this disease by uncovering its
      related genes. In this study, a graphic method was proposed to identify novel
      glioma related genes based on known glioma related genes. A weighted graph was
      constructed according to the protein-protein interaction information retrieved
      from STRING and the well-known shortest path algorithm was employed to discover
      novel genes. The following analysis suggests that some of them are related to the
      biological process of glioma, proving that our method was effective in
      identifying novel glioma related genes. We hope that the proposed method would be
      applied to study other diseases and provide useful information to medical
      workers, thereby designing effective treatments of different diseases. 

PMID- 25050378
TI  - Matrix metalloproteinases and their multiple roles in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent type of dementia. Pathological
      changes in the AD brain include amyloid-beta (Abeta) plaques and neurofibrillary
      tangles (NFTs), as well as neuronal death and synaptic loss. Matrix
      metalloproteinases (MMPs) play an important role as inflammatory components in
      the pathogenesis of AD. MMP-2 might be assumed to have a protective role in AD
      and is the major MMP which is directly linked to Abeta in the brain. Synthesis of
      MMP-9 can be induced by Abeta, and the enzymes appear to exert multiple effects
      in AD in senile plaque homoeostasis. The proaggregatory influence on tau oligomer
      formation in strategic brain regions may be a potential neurotoxic side effect of
      MMP-9. MMP-3 levels are correlated to the duration of AD and correlate with the
      CSF T-tau and P-tau levels in the elderly controls. Elevated brain levels of MMP
      3 might result in increased MMP-9 activity and indirectly facilitate tau
      aggregation. At present, the clinical utility of these proteins, particularly in
      plasma or serum, as potential early diagnostic biomarkers for AD remains to be
      established. More research is needed to understand the diverse roles of these
      proteases to design specific drugs and devise therapeutic strategies for AD. 

PMID- 25050379
TI  - Development and characterization of polyphenon 60 and caffeine microemulsion for
      enhanced antibacterial activity.
AB  - Green tea catechins and caffeine have exhibited antibacterial activity; however,
      their use is limited by lack of stability and effective delivery systems.
      Polyphenon 60 (P60) and caffeine were encapsulated in a single microemulsion (ME)
      formulation with an objective to lower the minimum inhibitory concentrations
      (MICs) of the individual agents against selected pathogens (S. epidermidis and E.
      coli). Combination of two natural compounds would advocate two different
      mechanisms on the bacterial growth thereby providing for better antibacterial
      activity. Thermodynamically stable ME was developed and characterized with an
      average particle size of 17.58 nm, further confirmed by TEM analysis.
      Antibacterial studies included chequerboard microdilution assay to determine the
      MIC and fractional inhibitory concentration (FIC) of both the natural compounds
      individually and in combination. MIC and FIC results indicated that the
      combination of the above two natural compounds was proficient in lowering the
      MICs of individual agents. Results of DPPH assay indicated that ME system
      preserved the long term antioxidative potential of P60 and caffeine. The
      cytotoxicity of the optimized formulation on Vero cell line by MTT assay was
      found to be nontoxic to mammalian cells.

PMID- 25050381
TI  - A novel dynamic update framework for epileptic seizure prediction.
AB  - Epileptic seizure prediction is a difficult problem in clinical applications, and
      it has the potential to significantly improve the patients' daily lives whose
      seizures cannot be controlled by either drugs or surgery. However, most current
      studies of epileptic seizure prediction focus on high sensitivity and low false
      positive rate only and lack the flexibility for a variety of epileptic seizures
      and patients' physical conditions. Therefore, a novel dynamic update framework
      for epileptic seizure prediction is proposed in this paper. In this framework,
      two basic sample pools are constructed and updated dynamically. Furthermore, the
      prediction model can be updated to be the most appropriate one for the prediction
      of seizures' arrival. Mahalanobis distance is introduced in this part to solve
      the problem of side information, measuring the distance between two data sets. In
      addition, a multichannel feature extraction method based on Hilbert-Huang
      transform and extreme learning machine is utilized to extract the features of a
      patient's preseizure state against the normal state. At last, a dynamic update
      epileptic seizure prediction system is built up. Simulations on Freiburg database
      show that the proposed system has a better performance than the one without
      update. The research of this paper is significantly helpful for clinical
      applications, especially for the exploitation of online portable devices. 

PMID- 25050380
TI  - Treatment of cardiovascular disease by traditional Chinese medicine against
      pregnane X receptor.
AB  - Recently, cardiovascular disease, also known as loop circulatory system diseases
      or disorders, is one of the serious diseases including heart disease, stroke,
      atherosclerosis, myocardial infarction, hypertension, hypotension, and
      thrombosis. Human pregnane X receptor, PXR, plays a crucial role in exogenous and
      endobiotic metabolism for rabbit, rat, mouse, and human. The PXR activation can
      protect the blood vessels from damage of hazardous substances. In this study we
      aim to investigate the potent lead compounds as PXR receptor agonist against
      cardiovascular disease. To improve drug development of TCM compounds, we aim to
      investigate the potent lead compounds as PXR agonists from the TCM compounds in
      TCM Database@Taiwan. The top three TCM compounds, bis(4-hydroxybenzyl) ether mono
      beta-D-glucopyranoside (BEMG), ixerisoside, and tangshenoside II, have displayed
      higher potent binding affinities than the positive control, PNU-142721, in the
      docking simulation. After MD simulations, which can optimize the result of
      docking simulation and validate the stability of H-bonds between each ligand and
      PXR protein under dynamic conditions, top TCM compounds, BEMG and tangshenoside
      II, maintain most of interactions with PXR protein, which keep the ligand binding
      stable in the binding domain. Hence, we propose BEMG and tangshenoside II as
      potential lead compounds for further study in drug development process with the
      PXR protein. 

PMID- 25050382
TI  - Ischemia-reperfusion injury and anesthesia.

PMID- 25050383
TI  - Impact of underweight after treatment on prognosis of advanced-stage ovarian
      cancer.
AB  - This study aimed to investigate the impact of underweight status on the prognosis
      of advanced-stage ovarian cancer. A total of 360 patients with stage III-IV
      epithelial ovarian cancer were enrolled and divided into three groups by body
      mass indexes (BMIs): underweight (BMI < 18.5 kg/m(2)); normal weight to
      overweight (18.5 kg/m(2) BMI < 27.5 kg/m(2)); obesity (BMI >= 27.5 kg/m(2)).
      Progression-free survival (PFS), overall survival (OS), CA-125, and neutrophil to
      lymphocyte ratio (NLR) as a marker reflecting host inflammation and immunity were
      compared among the three groups according to the three treatment times: at
      diagnosis; after surgery; and after treatment. Only underweight status after
      treatment was associated with poor OS in comparison with normal weight to
      overweight or obesity (mean value, 44.9 versus 78.8 or 67.4 months; P = 0.05); it
      was also an unfavorable factor for OS (adjusted HR, 2.29; 95% CI, 1.08-4.85).
      Furthermore, NLR was higher in patients with underweight than in those with
      obesity after treatment (median value, 2.15 versus 1.47; P = 0.03), in spite of
      no difference in CA-125 among the three groups at the three treatment times. In
      conclusion, underweight status after treatment may be a poor prognostic factor in
      patients with advanced-stage ovarian cancer, which accompanies increased host
      inflammation and decreased immunity. 

PMID- 25050384
TI  - Hsp74, a potential bladder cancer marker, has direct interaction with keratin 1.
AB  - Early diagnosis and prognosis monitoring are very important for the survival of
      patients with bladder cancer. To identify candidate biomarkers of bladder cancer,
      we used a combination of techniques including 2-DE, co-IP, western blot, LC
      MS/MS, and immunohistochemistry. Hsp74 was identified with high expression in
      bladder cancer. The cellular location of expression products of gene Hsp74 showed
      that they were distributed into cytoplasm and keratin 1 was found to be
      associated with Hsp74. The results provide a new idea to understand the molecular
      basis of bladder cancer progression and pinpoint new potential molecular target
      for early diagnosis and therapeutic monitoring of bladder cancer. 

PMID- 25050385
TI  - N2O emissions from an apple orchard in the coastal area of Bohai Bay, China.
AB  - Using static chambers and gas chromatography, nitrous oxide (N2O) fluxes from an
      apple orchard soil in the Bohai Bay region of China were measured from February
      2010 to February 2011. In this study, two nitrogen (N) fertilizer treatments were
      designed--without (CK) or with (SN) synthetic N fertilizers (800 kg N ha(-1)).
      The annual cumulative N2O emissions from CK and SN were 34.6 +/- 3.0 (mean +/-
      standard error) and 44.3 +/- 6.0 kg N2O-N ha(-1), respectively. Such high
      emissions resulted from the intensive N fertilization in the experimental and
      previous years. The direct emission factor (EFd) of N2O induced by the applied
      synthetic N fertilizers was 1.2%. The EFd is within the range of previous studies
      carried out in other croplands, which suggests that it is reasonable to estimate
      regional N2O emissions from apple orchards using the EFd obtained in other
      croplands. In addition, significant positive correlations existed between N2O
      fluxes and soil temperatures or soil dissolved organic carbon contents.

PMID- 25050386
TI  - Swarm intelligence and its applications 2014.

PMID- 25050388
TI  - Design and analysis of tubular permanent magnet linear wave generator.
AB  - Due to the lack of mature design program for the tubular permanent magnet linear
      wave generator (TPMLWG) and poor sinusoidal characteristics of the air gap flux
      density for the traditional surface-mounted TPMLWG, a design method and a new
      secondary structure of TPMLWG are proposed. An equivalent mathematical model of
      TPMLWG is established to adopt the transformation relationship between the linear
      velocity of permanent magnet rotary generator and the operating speed of TPMLWG,
      to determine the structure parameters of the TPMLWG. The new secondary structure
      of the TPMLWG contains surface-mounted permanent magnets and the interior
      permanent magnets, which form a series-parallel hybrid magnetic circuit, and
      their reasonable structure parameters are designed to get the optimum pole-arc
      coefficient. The electromagnetic field and temperature field of TPMLWG are
      analyzed using finite element method. It can be included that the sinusoidal
      characteristics of air gap flux density of the new secondary structure TPMLWG are
      improved, the cogging force as well as mechanical vibration is reduced in the
      process of operation, and the stable temperature rise of generator meets the
      design requirements when adopting the new secondary structure of the TPMLWG. 

PMID- 25050387
TI  - Antimicrobial edible films and coatings for meat and meat products preservation.
AB  - Animal origin foods are widely distributed and consumed around the world due to
      their high nutrients availability but may also provide a suitable environment for
      growth of pathogenic and spoilage microorganisms. Nowadays consumers demand high
      quality food with an extended shelf life without chemical additives. Edible films
      and coatings (EFC) added with natural antimicrobials are a promising preservation
      technology for raw and processed meats because they provide good barrier against
      spoilage and pathogenic microorganisms. This review gathers updated research
      reported over the last ten years related to antimicrobial EFC applied to meat and
      meat products. In addition, the films gas barrier properties contribute to
      extended shelf life because physicochemical changes, such as color, texture, and
      moisture, may be significantly minimized. The effectiveness showed by different
      types of antimicrobial EFC depends on meat source, polymer used, film barrier
      properties, target microorganism, antimicrobial substance properties, and storage
      conditions. The perspective of this technology includes tailoring of coating
      procedures to meet industry requirements and shelf life increase of meat and meat
      products to ensure quality and safety without changes in sensory characteristics.

PMID- 25050389
TI  - Effects of lower limb length and body proportions on the energy cost of
      overground walking in older persons.
AB  - BACKGROUND: Although walking has been extensively investigated in its
      biomechanical and physiological aspects, little is known on whether lower limb
      length and body proportions affect the energy cost of overground walking in older
      persons. METHODS: We enrolled 50 men and 12 women aged 65 years and over, mean
      69.1 +/- SD 5.4, who at the end of their cardiac rehabilitation program performed
      the six-minute walk test while wearing a portable device for direct calorimetry
      and who walked a distance comparable to that of nondisabled community-dwelling
      older persons. RESULTS: In the multivariable regression model (F = 12.75, P <
      0.001, adjusted R(2) = 0.278) the energy cost of overground walking, expressed as
      the net energy expenditure, in kg(-1) sec(-1), needed to provide own body mass
      with 1 joule kinetic energy, was inversely related to lower limb length and
      directly related to lower limb length to height ratio (beta +/- SE(beta) = -3.72
      * 10(-3) +/- 0.74 * 10(-3), P < 0.001, and 6.61 * 10(-3) +/- 2.14 * 10(-3), P =
      0.003, resp.). Ancillary analyses also showed that, altogether, 1 cm increase in
      lower limb length reduced the energy cost of overground walking by 2.57% (95%CI
      2.35-2.79). CONCLUSIONS: Lower limb length and body proportions actually affect
      the energy cost of overground walking in older persons.

PMID- 25050390
TI  - Dynamic metabolic changes during the first 3 months after 90Y-ibritumomab
      tiuxetan radioimmunotherapy.
AB  - OBJECTIVE: To elucidate the time course of tumor metabolism during the first 3
      months after (90)Y-ibritumomab tiuxetan radioimmunotherapy (RIT) in patients with
      refractory malignant lymphoma. MATERIALS AND METHODS: Seven patients with
      recurrent follicular lymphoma underwent FDG-PET imaging before and after 1-, 4-,
      and 12-week RIT with (90)Y-ibritumomab tiuxetan. Tumor metabolic activity on FDG
      PET scans was assessed as the maximum standard uptake value (SUVmax). RESULTS:
      Decrease in metabolism was detected 1 week after RIT. In the most decreased
      lesion, SUVmax decreased to 20% of the baseline value during the first week. Most
      lesions continued to decrease for up to 4 weeks. Some lesions showed increased
      metabolism from 4 to 12 weeks, while the level of FDG accumulations at 12 weeks
      was still lower than the baseline. CONCLUSIONS: Tumor response to RIT could be
      observed as early as 1 week after the administration of RIT. After tumor activity
      decreases, the metabolism may increase at least between 4 and 12 weeks. It
      suggests that the metabolic changes should be carefully evaluated during this
      period.

PMID- 25050391
TI  - Antihepatitis B virus activity of a protein-enriched fraction from housefly
      (Musca domestica) in a stable HBV-producing cell line.
AB  - Hepatitis B virus (HBV) infection remains a major public health problem. Although
      several vaccines and therapeutic strategies are currently being implemented to
      combat HBV virus, effective antiviral therapy against HBV infection has not been
      fully developed. Alternative strategies and new drugs to combat this disease are
      urged. Insects and insect derivatives are a large and unexploited source of
      potentially useful compounds for modern medicine. In the present study, we
      investigated the first anti-HBV activity of a protein-enriched fraction (PE) from
      the larvae of the housefly (Musca domestica) in a stable HBV-producing cell line.
      HBsAg and HBeAg in the culture medium were measured by enzyme-linked
      immunosorbent assay. HBV-DNA was quantified by fluorescent quantification PCR.
      HBV core protein was assayed by immunofluorescent staining. Results indicate PE
      treatment inhibited both HBsAg, HBeAg secretion, and HBV-DNA replication.
      Furthermore, PE could also suppress HBV core protein expression. PE could be a
      potential candidate for the development of a novel and effective drug for the
      treatment of HBV infection. 

PMID- 25050392
TI  - Development of a highly biocompatible antituberculosis nanodelivery formulation
      based on para-aminosalicylic acid-zinc layered hydroxide nanocomposites.
AB  - Tuberculosis is a lethal epidemic, difficult to control disease, claiming
      thousands of lives every year. We have developed a nanodelivery formulation based
      on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate
      salt as a precursor. The developed formulation has a fourfold higher efficacy of
      PAS against mycobacterium tuberculosis with a minimum inhibitory concentration
      (MIC) found to be at 1.40 MUg/mL compared to the free drug PAS with a MIC of 5.0
      MUg/mL. The newly developed formulation was also found active against Gram
      positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation
      was also found to be biocompatible with human normal lung cells MRC-5 and mouse
      fibroblast cells-3T3. The in vitro release of PAS from the formulation was found
      to be sustained in a human body simulated phosphate buffer saline (PBS) solution
      at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using
      zinc nitrate salt was advantageous in terms of yield and free from toxic zinc
      oxide contamination and had higher biocompatibility compared to one prepared
      using a zinc oxide precursor. In summary, these promising in vitro results are
      highly encouraging for the continued investigation of para-aminosalicylic acid
      and zinc layered hydroxide nanocomposites in vivo and eventual preclinical
      studies.

PMID- 25050393
TI  - A comparative study of routing protocols of heterogeneous wireless sensor
      networks.
AB  - Recently, heterogeneous wireless sensor network (HWSN) routing protocols have
      drawn more and more attention. Various HWSN routing protocols have been proposed
      to improve the performance of HWSNs. Among these protocols, hierarchical HWSN
      routing protocols can improve the performance of the network significantly. In
      this paper, we will evaluate three hierarchical HWSN protocols proposed recently-
      EDFCM, MCR, and EEPCA--together with two previous classical routing protocols-
      LEACH and SEP. We mainly focus on the round of the first node dies (also called
      the stable period) and the number of packets sent to sink, which is an important
      aspect to evaluate the monitoring ability of a protocol. We conduct a lot of
      experiments and simulations on Matlab to analyze the performance of the five
      routing protocols.

PMID- 25050394
TI  - HPM-based dynamic sparse grid approach for Perona-Malik equation.
AB  - The Perona-Malik equation is a famous image edge-preserved denoising model, which
      is represented as a nonlinear 2-dimension partial differential equation. Based on
      the homotopy perturbation method (HPM) and the multiscale interpolation theory, a
      dynamic sparse grid method for Perona-Malik was constructed in this paper.
      Compared with the traditional multiscale numerical techniques, the proposed
      method is independent of the basis function. In this method, a dynamic choice
      scheme of external grid points is proposed to eliminate the artifacts introduced
      by the partitioning technique. In order to decrease the calculation amount
      introduced by the change of the external grid points, the Newton interpolation
      technique is employed instead of the traditional Lagrange interpolation operator,
      and the condition number of the discretized matrix different equations is taken
      into account of the choice of the external grid points. Using the new numerical
      scheme, the time complexity of the sparse grid method for the image denoising is
      decreased to O(4 (J+2j)) from O(4(3J)), (j ? J). The experiment results show that
      the dynamic choice scheme of the external gird points can eliminate the boundary
      effect effectively and the efficiency can also be improved greatly comparing with
      the classical interval wavelets numerical methods.

PMID- 25050395
TI  - Effect of the key mixture parameters on shrinkage of reactive powder concrete.
AB  - Reactive powder concrete (RPC) mixtures are reported to have excellent mechanical
      and durability characteristics. However, such concrete mixtures having high
      amount of cementitious materials may have high early shrinkage causing cracking
      of concrete. In the present work, an attempt has been made to study the
      simultaneous effects of three key mixture parameters on shrinkage of the RPC
      mixtures. Considering three different levels of the three key mixture factors, a
      total of 27 mixtures of RPC were prepared according to 3(3) factorial experiment
      design. The specimens belonging to all 27 mixtures were monitored for shrinkage
      at different ages over a total period of 90 days. The test results were plotted
      to observe the variation of shrinkage with time and to see the effects of the key
      mixture factors. The experimental data pertaining to 90-day shrinkage were used
      to conduct analysis of variance to identify significance of each factor and to
      obtain an empirical equation correlating the shrinkage of RPC with the three key
      mixture factors. The rate of development of shrinkage at early ages was higher.
      The water to binder ratio was found to be the most prominent factor followed by
      cement content with the least effect of silica fume content. 

PMID- 25050396
TI  - Many local pattern texture features: which is better for image-based multilabel
      human protein subcellular localization classification?
AB  - Human protein subcellular location prediction can provide critical knowledge for
      understanding a protein's function. Since significant progress has been made on
      digital microscopy, automated image-based protein subcellular location
      classification is urgently needed. In this paper, we aim to investigate more
      representative image features that can be effectively used for dealing with the
      multilabel subcellular image samples. We prepared a large multilabel
      immunohistochemistry (IHC) image benchmark from the Human Protein Atlas database
      and tested the performance of different local texture features, including
      completed local binary pattern, local tetra pattern, and the standard local
      binary pattern feature. According to our experimental results from binary
      relevance multilabel machine learning models, the completed local binary pattern,
      and local tetra pattern are more discriminative for describing IHC images when
      compared to the traditional local binary pattern descriptor. The combination of
      these two novel local pattern features and the conventional global texture
      features is also studied. The enhanced performance of final binary relevance
      classification model trained on the combined feature space demonstrates that
      different features are complementary to each other and thus capable of improving
      the accuracy of classification. 

PMID- 25050397
TI  - Strongly lacunary ward continuity in 2-normed spaces.
AB  - A function f defined on a subset E of a 2-normed space X is strongly lacunary
      ward continuous if it preserves strongly lacunary quasi-Cauchy sequences of
      points in E; that is, (f(x k)) is a strongly lacunary quasi-Cauchy sequence
      whenever (x k) is strongly lacunary quasi-Cauchy. In this paper, not only
      strongly lacunary ward continuity, but also some other kinds of continuities are
      investigated in 2-normed spaces.

PMID- 25050398
TI  - Mine land reclamation and eco-reconstruction in Shanxi province I: mine land
      reclamation model.
AB  - Coal resource is the main primary energy in our country, while Shanxi Province is
      the most important province in resource. Therefore Shanxi is an energy base for
      our country and has a great significance in energy strategy. However because of
      the heavy development of the coal resource, the ecological environment is
      worsening and the farmland is reducing continuously in Shanxi Province. How to
      resolve the contradiction between coal resource exploitation and environmental
      protection has become the imperative. Thus the concept of "green mining industry"
      is arousing more and more attention. In this assay, we will talk about the basic
      mode of land reclamation in mine area, the engineering study of mine land
      reclamation, the comprehensive model study of mine land reclamation, and the
      design and model of ecological agricultural reclamation in mining subsidence. 

PMID- 25050399
TI  - A novel wide-area backup protection based on fault component current distribution
      and improved evidence theory.
AB  - In order to solve the problems of the existing wide-area backup protection (WABP)
      algorithms, the paper proposes a novel WABP algorithm based on the distribution
      characteristics of fault component current and improved Dempster/Shafer (D-S)
      evidence theory. When a fault occurs, slave substations transmit to master
      station the amplitudes of fault component currents of transmission lines which
      are the closest to fault element. Then master substation identifies suspicious
      faulty lines according to the distribution characteristics of fault component
      current. After that, the master substation will identify the actual faulty line
      with improved D-S evidence theory based on the action states of traditional
      protections and direction components of these suspicious faulty lines. The
      simulation examples based on IEEE 10-generator-39-bus system show that the
      proposed WABP algorithm has an excellent performance. The algorithm has low
      requirement of sampling synchronization, small wide-area communication flow, and
      high fault tolerance. 

PMID- 25050400
TI  - A new multiconstraint method for determining the optimal cable stresses in cable
      stayed bridges.
AB  - Cable-stayed bridges are one of the most popular types of long-span bridges. The
      structural behaviour of cable-stayed bridges is sensitive to the load
      distribution between the girder, pylons, and cables. The determination of
      pretensioning cable stresses is critical in the cable-stayed bridge design
      procedure. By finding the optimum stresses in cables, the load and moment
      distribution of the bridge can be improved. In recent years, different research
      works have studied iterative and modern methods to find optimum stresses of
      cables. However, most of the proposed methods have limitations in optimising the
      structural performance of cable-stayed bridges. This paper presents a
      multiconstraint optimisation method to specify the optimum cable forces in cable
      stayed bridges. The proposed optimisation method produces less bending moments
      and stresses in the bridge members and requires shorter simulation time than
      other proposed methods. The results of comparative study show that the proposed
      method is more successful in restricting the deck and pylon displacements and
      providing uniform deck moment distribution than unit load method (ULM). The final
      design of cable-stayed bridges can be optimised considerably through proposed
      multiconstraint optimisation method. 

PMID- 25050401
TI  - Electrochemical properties of chemically processed SiO x as coating material in
      lithium-ion batteries with Si anode.
AB  - A SiO x coating material for Si anode in lithium-ion battery was processed by
      using SiCl4 and ethylene glycol. The produced SiO x particles after heat
      treatment at 725 degrees C for 1 h were porous and irregularly shaped with
      amorphous structure. Pitch carbon added to SiO x was found to strongly affect
      solid electrolyte interphase stabilization and cyclic stability. When mixed with
      an optimal amount of 30 wt% pitch carbon, the SiO x showed a high
      charge/discharge cyclic stability of about 97% for the 2nd to the 50th cycle. The
      initial specific capacity of the SiO x was measured to be 1401 mAh/g. On the
      basis of the evaluation of the SiO x coating material, the process utilized in
      this study is considered an efficient method to produce SiO x with high
      performance in an economical way.

PMID- 25050403
TI  - Optimization of processing parameters for extraction of amylase enzyme from
      dragon (Hylocereus polyrhizus) peel using response surface methodology.
AB  - The main goal of this study was to investigate the effect of extraction
      conditions on the enzymatic properties of thermoacidic amylase enzyme derived
      from dragon peel. The studied extraction variables were the buffer-to-sample
      (B/S) ratio (1:2 to 1:6, w/w), temperature (-18 degrees C to 25 degrees ), mixing
      time (60 to 180 seconds), and the pH of the buffer (2.0 to 8.0). The results
      indicate that the enzyme extraction conditions exhibited the least significant (P
      < 0.05) effect on temperature stability. Conversely, the extraction conditions
      had the most significant (P < 0.05) effect on the specific activity and pH
      stability. The results also reveal that the main effect of the B/S ratio,
      followed by its interaction with the pH of the buffer, was significant (P < 0.05)
      among most of the response variables studied. The optimum extraction condition
      caused the amylase to achieve high enzyme activity (648.4 U), specific activity
      (14.2 U/mg), temperature stability (88.4%), pH stability (85.2%), surfactant
      agent stability (87.2%), and storage stability (90.3%).

PMID- 25050402
TI  - Genetic diversity in Passiflora species assessed by morphological and its
      sequence analysis.
AB  - This study used morphological characterization and phylogenetic analysis of the
      internal transcribed spacer (ITS) region of nuclear ribosomal DNA to investigate
      the phylogeny of Passiflora species. The samples were collected from various
      regions of East Malaysia, and discriminant function analysis based on linear
      combinations of morphological variables was used to classify the Passiflora
      species. The biplots generated five distinct groups discriminated by
      morphological variables. The group consisted of cultivars of P. edulis with high
      levels of genetic similarity; in contrast, P. foetida was highly divergent from
      other species in the morphological biplots. The final dataset of aligned
      sequences from nine studied Passiflora accessions and 30 other individuals
      obtained from GenBank database (NCBI) yielded one most parsimonious tree with two
      strongly supported clades. Maximum parsimony (MP) tree showed the phylogenetic
      relationships within this subgenus Passiflora support the classification at the
      series level. The constructed phylogenic tree also confirmed the divergence of P.
      foetida from all other species and the closeness of wild and cultivated species.
      The phylogenetic relationships were consistent with results of morphological
      assessments. The results of this study indicate that ITS region analysis
      represents a useful tool for evaluating genetic diversity in Passiflora at the
      species level. 

PMID- 25050405
TI  - Power control for direct-driven permanent magnet wind generator system with
      battery storage.
AB  - The objective of this paper is to construct a wind generator system (WGS) loss
      model that addresses the loss of the wind turbine and the generator. It aims to
      optimize the maximum effective output power and turbine speed. Given that the
      wind generator system has inertia and is nonlinear, the dynamic model of the wind
      generator system takes the advantage of the duty of the Buck converter and
      employs feedback linearization to design the optimized turbine speed tracking
      controller and the load power controller. According to that, this paper proposes
      a dual-mode dynamic coordination strategy based on the auxiliary load to reduce
      the influence of mode conversion on the lifetime of the battery. Optimized speed
      and power rapid tracking as well as the reduction of redundant power during mode
      conversion have gone through the test based on a 5 kW wind generator system test
      platform. The generator output power as the capture target has also been proved
      to be efficient.

PMID- 25050404
TI  - Traditional uses, chemical constituents, and biological activities of Bixa
      orellana L.: a review.
AB  - Bixa orellana L., popularly known as "urucum," has been used by indigenous
      communities in Brazil and other tropical countries for several biological
      applications, which indicates its potential use as an active ingredient in
      pharmaceutical products. The aim of this work was to report the main evidence
      found in the literature, concerning the ethnopharmacology, the biological
      activity, and the phytochemistry studies related to Bixa orellana L. Therefore,
      this work comprises a systematic review about the use of Bixa orellana in the
      American continent and analysis of the data collected. This study shows the well
      characterized pharmacological actions that may be considered relevant for the
      future development of an innovative therapeutic agent. 

PMID- 25050406
TI  - Evaluation of fatigue life of CRM-reinforced SMA and its relationship to dynamic
      stiffness.
AB  - Fatigue cracking is an essential problem of asphalt concrete that contributes to
      pavement damage. Although stone matrix asphalt (SMA) has significantly provided
      resistance to rutting failure, its resistance to fatigue failure is yet to be
      fully addressed. The aim of this study is to evaluate the effect of crumb rubber
      modifier (CRM) on stiffness and fatigue properties of SMA mixtures at optimum
      binder content, using four different modification levels, namely, 6%, 8%, 10%,
      and 12% CRM by weight of the bitumen. The testing undertaken on the asphalt mix
      comprises the dynamic stiffness (indirect tensile test), dynamic creep (repeated
      load creep), and fatigue test (indirect tensile fatigue test) at temperature of
      25 degrees C. The indirect tensile fatigue test was conducted at three different
      stress levels (200, 300, and 400 kPa). Experimental results indicate that CRM
      reinforced SMA mixtures exhibit significantly higher fatigue life compared to the
      mixtures without CRM. Further, higher correlation coefficient was obtained
      between the fatigue life and resilient modulus as compared to permanent strain;
      thus resilient modulus might be a more reliable indicator in evaluating the
      fatigue life of asphalt mixture.

PMID- 25050408
TI  - The technical efficiency of specialised milk farms: a regional view.
AB  - The aim of the article is to evaluate production efficiency and its determinants
      of specialised dairy farming among the EU regions. In the most of European
      regions, there is a relatively high significance of small specialised farms
      including dairy farms. The DEAVRS method (data envelopment analysis with variable
      returns to scale) reveals efficient and inefficient regions including the scale
      efficiency. In the next step, the two-sample t-test determines differences of
      economic and structural indicators between efficient and inefficient regions. The
      research reveals that substitution of labour by capital/contract work explains
      the variability of the farm net value added per AWU (annual work unit) income
      indicator by more than 30%. The significant economic determinants of production
      efficiency in specialised dairy farming are farm size, herd size, crop output per
      hectare, productivity of energy, and capital (at alpha = 0.01). Specialised dairy
      farms in efficient regions have significantly higher farm net value added per AWU
      than inefficient regions. Agricultural enterprises in inefficient regions have a
      more extensive structure and produce more noncommodity output (public goods).
      Specialised dairy farms in efficient regions have a slightly higher milk yield,
      specific livestock costs of feed, bedding, and veterinary services per livestock
      unit. 

PMID- 25050407
TI  - Prediction of four kinds of simple supersecondary structures in protein by using
      chemical shifts.
AB  - Knowledge of supersecondary structures can provide important information about
      its spatial structure of protein. Some approaches have been developed for the
      prediction of protein supersecondary structure. However, the feature used by
      these approaches is primarily based on amino acid sequences. In this study, a
      novel model is presented to predict protein supersecondary structure by use of
      chemical shifts (CSs) information derived from nuclear magnetic resonance (NMR)
      spectroscopy. Using these CSs as inputs of the method of quadratic discriminant
      analysis (QD), we achieve the overall prediction accuracy of 77.3%, which is
      competitive with the same method for predicting supersecondary structures from
      amino acid compositions in threefold cross-validation. Moreover, our finding
      suggests that the combined use of different chemical shifts will influence the
      accuracy of prediction. 

PMID- 25050409
TI  - A study on the chiral inversion of mandelic acid in humans.
AB  - Mandelic acid is a chiral metabolite of the industrial pollutant styrene and is
      used in chemical skin peels, as a urinary antiseptic and as a component of other
      medicines. In humans, S-mandelic acid undergoes rapid chiral inversion to R
      mandelic acid by an undefined pathway but it has been proposed to proceed via the
      acyl-CoA esters, S- and R-2-hydroxy-2-phenylacetyl-CoA, in an analogous pathway
      to that for Ibuprofen. This study investigates chiral inversion of mandelic acid
      using purified human recombinant enzymes known to be involved in the Ibuprofen
      chiral inversion pathway. Both S- and R-2-hydroxy-2-phenylacetyl-CoA were
      hydrolysed to mandelic acid by human acyl-CoA thioesterase-1 and -2 (ACOT1 and
      ACOT2), consistent with a possible role in the chiral inversion pathway. However,
      human alpha-methylacyl-CoA racemase (AMACR; P504S) was not able to catalyse
      exchange of the alpha-proton of S- and R-2-hydroxy-2-phenylacetyl-CoA, a
      requirement for chiral inversion. Both S- and R-2-phenylpropanoyl-CoA were
      epimerised by AMACR, showing that it is the presence of the hydroxy group that
      prevents epimerisation of R- and S-2-hydroxy-2-phenylacetyl-CoAs. The results
      show that it is unlikely that 2-hydroxy-2-phenylacetyl-CoA is an intermediate in
      the chiral inversion of mandelic acid, and that the chiral inversion of mandelic
      acid is via a different pathway to that of Ibuprofen and related drugs. 

PMID- 25050410
TI  - Simultaneous determination of epinephrine and dopamine by electrochemical
      reduction on the hybrid material SiO2/graphene oxide decorated with Ag
      nanoparticles.
AB  - This paper describes the synthesis, characterization and applications of a new
      hybrid material composed of mesoporous silica (SiO2) modified with graphene oxide
      (GO), SiO2/GO, obtained by the sol-gel process using HF as the catalyst. The
      hybrid material, SiO2/GO, was decorated with silver nanoparticles (AgNPs) with a
      size of less than 20 nanometres, prepared directly on the surface of the material
      using N,N-dimethylformamide (DMF) as the reducing agent. The resulting material
      was designated as AgNP/SiO2/GO. The Ag/SiO2/GO material was characterized by X
      ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy
      dispersive X-ray (EDX) and high-resolution transmission electron microscopy (HR
      TEM). A glassy carbon electrode modified with AgNP/SiO2/GO was used in the
      development of a sensitive electrochemical sensor for the simultaneous
      determination of epinephrine and dopamine employing electrocatalytic reduction
      using squarewave voltammetry. Well-defined and separate reduction peaks were
      observed in PBS buffer at pH 7. No significant interference was seen for
      primarily biological interferents such as uric acid and ascorbic acid in the
      detection of dopamine and epinephrine. Our study demonstrated that the resultant
      AgNP/SiO2/GO-modified electrode is highly sensitive for the simultaneous
      determination of dopamine and epinephrine, with the limits of detection being
      0.26 and 0.27 MUmol L(-1), respectively. The AgNP/SiO2/GO-modified electrode is
      highly selective and can be used to detect dopamine and epinephrine in a human
      urine sample. 

PMID- 25050411
TI  - Fine structural features of nanoscale zero-valent iron characterized by spherical
      aberration corrected scanning transmission electron microscopy (Cs-STEM).
AB  - An angstrom-resolution physical model of nanoscale zero-valent iron (nZVI) is
      generated with a combination of spherical aberration corrected scanning
      transmission electron microscopy (Cs-STEM), selected area electron diffraction
      (SAED), energy-dispersive X-ray spectroscopy (EDS) and electron energy-loss
      spectroscopy (EELS) on the Fe L-edge. Bright-field (BF), high-angle annular dark
      field (HAADF) and secondary electron (SE) imaging of nZVI acquired by a Hitachi
      HD-2700 STEM show near atomic resolution images and detailed morphological and
      structural information of nZVI. The STEM-EDS technique confirms that the fresh
      nZVI comprises of a metallic iron core encapsulated with a thin layer of iron
      oxides or oxyhydroxides. SAED patterns of the Fe core suggest the polycrystalline
      structure in the metallic core and amorphous nature of the oxide layer.
      Furthermore, Fe L-edge of EELS shows varied structural features from the
      innermost Fe core to the outer oxide shell. A qualitative analysis of the Fe
      L(2,3) edge fine structures reveals that the shell of nZVI consists of a mixed
      Fe(II)/Fe(III) phase close to the Fe (0) interface and a predominantly Fe(III) at
      the outer surface of nZVI.

PMID- 25050412
TI  - Model based variable selection as a tool to highlight biological differences in
      Raman spectra of cells.
AB  - In vitro Raman spectroscopy used for non-invasive, non-destructive
      characterization of single cells and tissues has proven to be a powerful tool for
      understanding the complex biochemical processes within these biological systems.
      Additionally it enables the comparison of a wide range of in vitro model systems
      by discriminating them based on their biomolecular differences. However, one
      persistent challenge in Raman spectroscopy has been the highly complex structure
      of cell and tissue spectra, which comprise signals from lipids, proteins,
      carbohydrates and nucleic acids, which may overlap significantly. This leads to
      difficulty in discerning which molecular components are responsible for the
      changes seen between experimental groups. To address this problem, we introduce a
      technique to highlight the significant biochemical changes between sample groups
      by applying a novel approach using Partial Least Squares - Discriminant Analysis
      (PLS-DA) Variable Importance Projection (VIP) scores normally used for variable
      selection as heat maps combined with group difference spectra to highlight
      significant differences in Raman band shapes and position. To illustrate this
      method we analyzed single HeLa cells in their live, fixed, fixed and ethanol
      dehydrated, to the fixed, dehydrated and then rehydrated states respectively.
      Fixation, ethanol dehydration and rehydration are known to induce molecular
      changes in the lipids and proteins within each cell. 

PMID- 25050414
TI  - Ammonium betaines: efficient ionic nucleophilic catalysts for the ring-opening
      polymerization of L-lactide and cyclic carbonates.
AB  - The ionic nucleophilic character of ammonium betaine catalysts allows for
      controlling the ROP of L-LA for DP as high as 750 with very narrow dispersity
      values (<=1.18). Compared to ionic nucleophilic and hydrogen-bonding based
      catalysts for ROP, meta-betaine combines the positive aspects of both processes
      in terms of kinetics and selectivity. The versatility of ammonium betaines was
      evidenced by varying the nature of the initiating alcohol and monomer used.

PMID- 25050413
TI  - Lab-on-a-drop: biocompatible fluorescent nanoprobes of gold nanoclusters for
      label-free evaluation of phosphorylation-induced inhibition of
      acetylcholinesterase activity towards the ultrasensitive detection of pesticide
      residues.
AB  - A simple, sensitive, selective, and "lab-on-a-drop"-based fluorimetric protocol
      has been proposed using biocompatible fluorescent nanoprobes of gold nanoclusters
      (AuNCs) for the label-free evaluation of the catalytic activity and
      phosphorylation of acetylcholinesterase (AChE) under physiologically simulated
      environments. Protein-stabilized AuNCs were prepared and mixed with
      acetylthiocholine (ATC) serving as "a drop" of fluorimetric reaction substrate.
      The AChE-catalyzed hydrolysis of ATC releases thiocholine to cause the
      aggregation of the AuNCs towards a dramatic decrease in fluorescence intensities,
      which could be curbed by the phosphorylation-induced inhibition of AChE activity
      when exposed to organophosphorus compounds (OPs). The reaction procedures and
      conditions of AChE catalysis and phosphorylation were monitored by fluorimetric
      measurements and electron microscopy imaging. Moreover, a selective and
      ultrasensitive fluorimetric assay has been tailored for the detection of
      pesticide residues using dimethyl-dichloro-vinyl phosphate (DDVP) as an example.
      Investigation results indicate that the specific catalysis and irreversible OP
      induced phosphorylation of AChE, in combination with sensitive fluorimetric
      outputs could facilitate the detection of total free OPs with high selectivity
      and sensitivity. A linear concentration of DDVP ranging from 0.032 nM to 20 nM
      could be obtained with a detection limit of 13.67 pM. Particularly, pesticide
      residues of DDVP in vegetable samples were quantified down to ~36 pM. Such a
      label-free "lab-on-a drop"-based fluorimetry may promise wide applications for
      the evaluation of the physiological catalytic activity of various enzymes (i.e.,
      cholinesterase), and especially for monitoring the direct phosphorylation
      biomarkers of free OPs towards rapid and early warning, and accurate diagnosis of
      OP exposure.

PMID- 25050416
TI  - Ligand-controlled divergent formation of alkenyl- or allylboronates catalyzed by
      Pd, and synthetic applications.
AB  - The use of different ligands allows the preparation of either allyl- or
      alkenylboronates by Pd-catalyzed borylation of allylic carbonates containing
      alkyne groups. Unprecedented borylative cyclisation to alkenylboronates takes
      place with PCy3. The difficult dissociation of NHC ligands allows borylation of
      carbonates in the presence of alkynes. Oxidation, regioselective Suzuki coupling,
      as well as Au-catalyzed cycloisomerisation of boronates illustrate the potential
      synthetic applications of these reactions. 

PMID- 25050415
TI  - Structural elucidation of foldamers with no long range conformational order.
AB  - The synthesis and structural investigation of aromatic-aliphatic oligoamide
      foldamers reveals a zig-zag tape conformation with local conformational
      variability that precludes long range order. 

PMID- 25050417
TI  - The ring opening reaction of 1,3-dithiol-2-one systems is fully reversible.
AB  - The deprotection of a common precursor moiety in dithiolene chemistry was
      discovered to be fully reversible, which, besides being relevant for researchers
      working in very different fields with these non-innocent ligand systems, may even
      have an impact on CO2 housekeeping, as the deprotected ligand acts as an
      efficient trap. 

PMID- 25050418
TI  - A combined 77Se NMR and molecular dynamics contribution to the structural
      understanding of the chalcogenide glasses.
AB  - Solid-state (77)Se NMR measurements, first-principles molecular dynamics and DFT
      calculations of NMR parameters were performed to gain insight into the structure
      of selenium-rich GexSe(1-x) glasses. We recorded the fully-relaxed NMR spectra on
      natural abundance and 100% isotopically enriched GeSe4 samples, which led us to
      reconsider the level of structural heterogeneity in this material. In this paper,
      we propose an alternative procedure to initialise molecular dynamics runs for the
      chalcogenide glasses. The (77)Se NMR spectra calculated on the basis of the
      structural models deduced from these simulations are consistent with the
      experimental spectrum. 

PMID- 25050419
TI  - Lead-iodide nanowire perovskite with methylviologen showing interfacial charge
      transfer absorption: a DFT analysis.
AB  - Methylviologen lead-iodide perovskite (MVPb2I6) is a self-assembled one
      dimensional (1-D) material consisting of lead-iodide nanowires and intervening
      organic electron-accepting molecules, methylviologen (MV(2+)). MVPb2I6
      characteristically shows optical interfacial charge-transfer (ICT) transitions
      from the lead-iodide nanowire to MV(2+) in the visible region and unique
      ambipolar photoconductivity, in which electrons are transported through the three
      dimensional (3-D) organic network and holes along the 1-D lead-iodide nanowire.
      In this work, we theoretically study the electronic band-structure and
      photocarrier properties of MVPb2I6 by density functional theory (DFT)
      calculations. Our results clearly confirm the experimentally reported type-II
      band alignment, whose valence band mainly consists of 5p (I) orbitals of the lead
      iodide nanowires and the conduction band of the lowest unoccupied molecular
      orbital of MV(2+). The DFT calculation also reveals weak charge-transfer
      interactions between the lead-iodide nanowires and MV(2+). In addition, the
      electronic distributions of the valence and conduction bands indicate the 3-D
      transport of electrons and 1-D transport of holes, supporting the reported
      experimental result. 

PMID- 25050420
TI  - Charge separation energetics at organic heterojunctions: on the role of
      structural and electrostatic disorder.
AB  - Improving the performance of organic photovoltaic cells requires the
      individuation of the specific factors limiting their efficiency, by rationalizing
      the relationship between the chemical nature of the materials, their morphology,
      and the electronic processes taking place at their interface. In this
      contribution, we present recent theoretical advances regarding the determination
      of the energetics and dynamics of charge carriers at organic-organic interfaces,
      highlighting the role of structural and electrostatic disorder in the separation
      of electron-hole pairs. The influence of interfacial electrostatic interactions
      on charge carrier energetics is first illustrated in model aggregates. Then, we
      review some of our recent theoretical studies in which we combined molecular
      dynamics, quantum-chemical and classical micro-electrostatic methods to evaluate
      the energy landscape explored by the mobile charges in the vicinity of donor
      acceptor interfaces with realistic morphologies. Finally, we describe the
      theoretical challenges that still need to be overcome in order to gain a complete
      overview of the charge separation processes at the molecular level. 

PMID- 25050421
TI  - Facile synthesis of exfoliated Co-Al LDH-carbon nanotube composites with high
      performance as supercapacitor electrodes.
AB  - A novel sandwich-like structured Co-Al LDH-Carbon Nanotube (CNT) composite has
      been successfully synthesized by the elegant combination between exfoliated Co-Al
      LDH nanosheets and modified CNTs, which was achieved through an electrostatic
      assembly method. It is worth noting that the negatively charged CNTs, sandwiched
      between the positively charged nanosheets via the electrostatic force, can not
      only expand the area of contact of electrolyte ions but also highly improve the
      conductivity. The as-prepared Co-Al LDHs-CNTs composite exhibited a high specific
      capacitance of 884 F g(-1) and a good cycle stability over 2000 cycles.
      Therefore, such a facile synthetic route to fabricate the layered structure
      composite may open a new strategy to prepare other composites with largely
      enhanced electrochemical properties, which can be of great promise in energy
      storage device application. 

PMID- 25050422
TI  - Earliest stages of visual cortical processing are not modified by attentional
      load.
AB  - This study investigated the effects of attentional load on neural responses to
      attended and irrelevant visual stimuli by recording high-density event-related
      potentials (ERPs) from the scalp in normal adult subjects. Peripheral (upper and
      lower visual field) and central stimuli were presented in random order at a rapid
      rate while subjects responded to targets among the central stimuli. Color
      detection and color-orientation conjunction search tasks were used as the low-
      and high-load tasks, respectively. Behavioral results showed significant load
      effects on both accuracy and reaction time for target detections. ERP results
      revealed no significant load effect on the initial C1 component (60-100 ms)
      evoked by either central-relevant or peripheral-irrelevant stimuli. Source
      analysis with dipole modeling confirmed previous reports that the C1 includes the
      initial evoked response in primary visual cortex. Source analyses indicated that
      high attentional load enhanced the early (70-140 ms) neural response to central
      relevant stimuli in ventral-lateral extrastriate cortex, whereas load effects on
      peripheral-irrelevant stimulus processing started at 110 ms and were localized to
      more dorsal and anterior extrastriate cortical areas. These results provide
      evidence that the earliest stages of visual cortical processing are not modified
      by attentional load and show that attentional load affects the processing of task
      relevant and irrelevant stimuli in different ways.

PMID- 25050423
TI  - Multidimensional morphometric 3D MRI analyses for detecting brain abnormalities
      in children: impact of control population.
AB  - Automated morphometric approaches are used to detect epileptogenic structural
      abnormalities in 3D MR images in adults, using the variance of a control
      population to obtain z-score maps in an individual patient. Due to the
      substantial changes the developing human brain undergoes, performing such
      analyses in children is challenging. This study investigated six features derived
      from high-resolution T1 datasets in four groups: normal children (1.5T or 3T
      data), normal clinical scans (3T data), and patients with structural brain
      lesions (3T data), with each n = 10. Normative control data were obtained from
      the NIH study on normal brain development (n = 401). We show that control group
      size substantially influences the captured variance, directly impacting the
      patient's z-scores. Interestingly, matching on gender does not seem to be
      beneficial, which was unexpected. Using data obtained at higher field scanners
      produces slightly different base rates of suprathreshold voxels, as does using
      clinically derived normal studies, suggesting a subtle but systematic effect of
      both factors. Two approaches for controlling suprathreshold voxels in a
      multidimensional approach (combining features and requiring a minimum cluster
      size) were shown to be substantial and effective in reducing this number.
      Finally, specific strengths and limitations of such an approach could be
      demonstrated in individual cases.

PMID- 25050424
TI  - Developmental changes in effective connectivity associated with relational
      reasoning.
AB  - Rostrolateral prefrontal cortex (RLPFC) is part of a frontoparietal network of
      regions involved in relational reasoning, the mental process of working with
      relationships between multiple mental representations. RLPFC has shown functional
      and structural changes with age, with increasing specificity of left RLPFC
      activation for relational integration during development. Here, we used dynamic
      causal modeling (DCM) to investigate changes in effective connectivity during a
      relational reasoning task through the transition from adolescence into adulthood.
      We examined fMRI data of 37 healthy female participants (11-30 years old)
      performing a relational reasoning paradigm. Comparing relational integration to
      the manipulation of single relations revealed activation in five regions: the
      RLPFC, anterior insula, dorsolateral PFC, inferior parietal lobe, and medial
      superior frontal gyrus. We used a new exhaustive search approach and identified a
      full DCM model, which included all reciprocal connections between the five
      clusters in the left hemisphere, as the optimal model. In line with previous
      resting state fMRI results, we showed distinct developmental effects on the
      strength of long-range frontoparietal versus frontoinsular short-range fixed
      connections. The modulatory connections associated with relational integration
      increased with age. Gray matter volume in left RLPFC, which decreased with age,
      partly accounted for changes in fixed PFC connectivity. Finally, improvements in
      relational integration performance were associated with greater modulatory and
      weaker fixed PFC connectivity. This pattern provides further evidence of
      increasing specificity of left PFC function for relational integration compared
      to the manipulation of single relations, and demonstrates an association between
      effective connectivity and performance during development.

PMID- 25050425
TI  - Overlapping and distinct representations of advantageous and disadvantageous
      inequality.
AB  - Advantageous inequality (AI) aversion, or paying at a personal cost to achieve
      equal reward distribution, represents a unique feature of human behavior. Here,
      we show that individuals have strong preferences for fairness in both
      disadvantageous (DI) and advantageous inequality (AI) situations, such that they
      alter others' payoff at a personal financial cost. At the neural level, we found
      that both types of inequality activated the putamen, orbitofrontal cortex, and
      insula, regions implicated in motivation. Individual difference analyses found
      that those who spent more money to increase others' payoff had stronger activity
      in putamen when they encountered AI and less functional connectivity between
      putamen and both orbitofrontal cortex and anterior insula. Conversely, those who
      spent more money to reduce others' payoff had stronger activity in amygdala in
      response to DI and less functional connectivity between amygdala and ventral
      anterior cingulate cortex. These dissociations suggest that both types of
      inequality are processed by similar brain areas, yet modulated by different
      neural pathways.

PMID- 25050427
TI  - Idiopathic-generalized epilepsy shows profound white matter diffusion-tensor
      imaging alterations.
AB  - OBJECTIVES: Idiopathic-generalized epilepsy (IGE) is currently considered to be a
      genetic disease without structural alterations on conventional MRI. However,
      voxel-based morphometry has shown abnormalities in IGE. Another method to analyze
      the microstructure of the brain is diffusion-tensor imaging (DTI). We sought to
      clarify which structural alterations are present in IGE and the most frequent
      subsyndrome juvenile myoclonic epilepsy (JME). EXPERIMENTAL DESIGN: We studied 25
      patients (13 IGE and 12 JME) and 44 healthy controls with DTI. Fractional
      anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity (AD/RD) were
      calculated and group differences were analyzed using tract-based spatial
      statistics (TBSS). Additionally we performed a target-based classification of
      TBSS results based on the Freesurfer cortical regions. PRINCIPLE OBSERVATIONS:
      TBSS showed widespread FA reductions as well as MD and RD increases in patients
      compared to controls. Affected areas were corpus callosum, corticospinal tract,
      superior and inferior longitudinal fasciculus and supplementary motor regions. No
      significant differences were found between JME and IGE subgroups. The target
      based classification confirmed a particular involvement of the superior frontal
      gyrus (mesiofrontal area) in IGE/ME. CONCLUSIONS: IGE and JME patients showed
      clear microstructural alterations in several large white matter tracts. Similar
      findings have been reported in rodent models of IGE. Previous, region-of-interest
      based DTI studies may have under-estimated the spatial extent of structural loss
      associated with generalized epilepsy. The comparison of clinically defined JME
      and IGE groups revealed no significant DTI differences in our cohort.

PMID- 25050426
TI  - Functional dissociation of ventral frontal and dorsomedial default mode network
      components during resting state and emotional autobiographical recall.
AB  - Humans spend a substantial share of their lives mind-wandering. This spontaneous
      thinking activity usually comprises autobiographical recall, emotional, and self
      referential components. While neuroimaging studies have demonstrated that a
      specific brain "default mode network" (DMN) is consistently engaged by the
      "resting state" of the mind, the relative contribution of key cognitive
      components to DMN activity is still poorly understood. Here we used fMRI to
      investigate whether activity in neural components of the DMN can be
      differentially explained by active recall of relevant emotional autobiographical
      memories as compared with the resting state. Our study design combined emotional
      autobiographical memory, neutral memory and resting state conditions, separated
      by a serial subtraction control task. Shared patterns of activation in the DMN
      were observed in both emotional autobiographical and resting conditions, when
      compared with serial subtraction. Directly contrasting autobiographical and
      resting conditions demonstrated a striking dissociation within the DMN in that
      emotional autobiographical retrieval led to stronger activation of the
      dorsomedial core regions (medial prefrontal cortex, posterior cingulate cortex),
      whereas the resting state condition engaged a ventral frontal network (ventral
      striatum, subgenual and ventral anterior cingulate cortices) in addition to the
      IPL. Our results reveal an as yet unreported dissociation within the DMN. Whereas
      the dorsomedial component can be explained by emotional autobiographical memory,
      the ventral frontal one is predominantly associated with the resting state
      proper, possibly underlying fundamental motivational mechanisms engaged during
      spontaneous unconstrained ideation.

PMID- 25050429
TI  - Reduced anterior internal capsule white matter integrity in primary insomnia.
AB  - Chronic insomnia is one of the most prevalent central nervous system diseases,
      however, its neurobiology is poorly understood. Up to now, nothing is known about
      the integrity of white matter tracts in insomnia patients. In this study,
      diffusion tensor imaging (DTI) was used in a well-characterized sample of primary
      insomnia (PI) patients and good sleeper controls to fill this void. Voxelwise
      between-group comparisons of fractional anisotropy (FA) were performed in 24 PI
      patients (10 males; 14 females; 42.7 +/- 14.5 years) and 35 healthy good sleepers
      (15 males; 20 females; 40.1 +/- 9.1 years) with age and sex as covariates. PI
      patients showed reduced FA values within the right anterior internal capsule and
      a trend for reduced FA values in the left anterior internal capsule. The results
      suggest that insomnia is associated with a reduced integrity of white matter
      tracts in the anterior internal capsule indicating that disturbed fronto
      subcortical connectivity may be a cause or consequence of the disorder.

PMID- 25050430
TI  - Functional centrality of amygdala, striatum and hypothalamus in a "small-world"
      network underlying joy: an fMRI study with music.
AB  - Current knowledge about small-world networks underlying emotions is sparse, and
      confined to functional magnetic resonance imaging (fMRI) studies using resting
      state paradigms. This fMRI study applied Eigenvector Centrality Mapping (ECM) and
      functional connectivity analysis to reveal neural small-world networks underlying
      joy and fear. Joy and fear were evoked using music, presented in 4-min blocks.
      Results show that the superficial amygdala (SF), laterobasal amygdala (LB),
      striatum, and hypothalamus function as computational hubs during joy. Out of
      these computational hubs, the amygdala nuclei showed the highest centrality
      values. The SF showed functional connectivity during joy with the mediodorsal
      thalamus (MD) and nucleus accumbens (Nac), suggesting that SF, MD, and Nac
      modulate approach behavior in response to positive social signals such as joyful
      music. The striatum was functionally connected during joy with the LB, as well as
      with premotor cortex, areas 1 and 7a, hippocampus, insula and cingulate cortex,
      showing that sensorimotor, attentional, and emotional processes converge in the
      striatum during music perception. The hypothalamus showed functional connectivity
      during joy with hippocampus and MD, suggesting that hypothalamic endocrine
      activity is modulated by hippocampal and thalamic activity during sustained
      periods of music-evoked emotion. Our study indicates high centrality of the
      amygdala nuclei groups within a functional network underlying joy, suggesting
      that these nuclei play a central role for the modulation of emotion-specific
      activity within this network.

PMID- 25050428
TI  - Diagnosis of autism spectrum disorders using regional and interregional
      morphological features.
AB  - This article describes a novel approach to identify autism spectrum disorder
      (ASD) utilizing regional and interregional morphological patterns extracted from
      structural magnetic resonance images. Two types of features are extracted to
      characterize the morphological patterns: (1) Regional features, which includes
      the cortical thickness, volumes of cortical gray matter, and cortical-associated
      white matter regions, and several subcortical structures extracted from different
      regions-of-interest (ROIs); (2) Interregional features, which convey the
      morphological change pattern between pairs of ROIs. We demonstrate that the
      integration of regional and interregional features via multi-kernel learning
      technique can significantly improve the classification performance of ASD,
      compared with using either regional or interregional features alone.
      Specifically, the proposed framework achieves an accuracy of 96.27% and an area
      of 0.9952 under the receiver operating characteristic curve, indicating excellent
      diagnostic power and generalizability. The best performance is achieved when both
      feature types are weighted approximately equal, indicating complementary between
      these two feature types. Regions that contributed the most to classification are
      in line with those reported in the previous studies, particularly the subcortical
      structures that are highly associated with human emotional modulation and memory
      formation. The autistic brains demonstrate a significant rightward asymmetry
      pattern particularly in the auditory language areas. These findings are in
      agreement with the fact that ASD is a behavioral- and language-related
      neurodevelopmental disorder. By concurrent consideration of both regional and
      interregional features, the current work presents an effective means for better
      characterization of neurobiological underpinnings of ASD that facilitates its
      identification from typically developing children.

PMID- 25050431
TI  - Connectivity of the subthalamic nucleus and globus pallidus pars interna to
      regions within the speech network: a meta-analytic connectivity study.
AB  - Cortico-basal ganglia connections are involved in a range of behaviors within
      motor, cognitive, and emotional domains; however, the whole-brain functional
      connections of individual nuclei are poorly understood in humans. The first aim
      of this study was to characterize and compare the connectivity of the subthalamic
      nucleus (STN) and globus pallidus pars interna (GPi) using meta-analytic
      connectivity modeling. Structure-based activation likelihood estimation meta
      analyses were performed for STN and GPi seeds using archived functional imaging
      coordinates from the BrainMap database. Both regions coactivated with caudate,
      putamen, thalamus, STN, GPi, and GPe, SMA, IFG, and insula. Contrast analyses
      also revealed coactivation differences within SMA, IFG, insula, and premotor
      cortex. The second aim of this study was to examine the degree of overlap between
      the connectivity maps derived for STN and GPi and a functional activation map
      representing the speech network. To do this, we examined the intersection of
      coactivation maps and their respective contrasts (STN > GPi and GPi > STN) with a
      coordinate-based meta-analysis of speech function. In conjunction with the speech
      map, both STN and GPi coactivation maps revealed overlap in the anterior insula
      with GPi map additionally showing overlap in the supplementary motor area (SMA).
      Among cortical regions activated by speech tasks, STN was found to have stronger
      connectivity than GPi with regions involved in cognitive linguistic processes
      (pre-SMA, dorsal anterior insula, and inferior frontal gyrus), while GPi
      demonstrated stronger connectivity to regions involved in motor speech processes
      (middle insula, SMA, and premotor cortex).

PMID- 25050432
TI  - Neuronal oscillations and functional interactions between resting state networks.
AB  - Functional magnetic imaging (fMRI) studies showed that resting state activity in
      the healthy brain is organized into multiple large-scale networks encompassing
      distant regions. A key finding of resting state fMRI studies is the anti
      correlation typically observed between the dorsal attention network (DAN) and the
      default mode network (DMN), which - during task performance - are activated and
      deactivated, respectively. Previous studies have suggested that alcohol
      administration modulates the balance of activation/deactivation in brain
      networks, as well as it induces significant changes in oscillatory activity
      measured by electroencephalography (EEG). However, our knowledge of alcohol
      induced changes in band-limited EEG power and their potential link with the
      functional interactions between DAN and DMN is still very limited. Here we
      address this issue, examining the neuronal effects of alcohol administration
      during resting state by using simultaneous EEG-fMRI. Our findings show increased
      EEG power in the theta frequency band (4-8 Hz) after administration of alcohol
      compared to placebo, which was prominent over the frontal cortex. More
      interestingly, increased frontal tonic EEG activity in this band was associated
      with greater anti-correlation between the DAN and the frontal component of the
      DMN. Furthermore, EEG theta power and DAN-DMN anti-correlation were relatively
      greater in subjects who reported a feeling of euphoria after alcohol
      administration, which may result from a diminished inhibition exerted by the
      prefrontal cortex. Overall, our findings suggest that slow brain rhythms are
      responsible for dynamic functional interactions between brain networks. They also
      confirm the applicability and potential usefulness of EEG-fMRI for central
      nervous system drug research.

PMID- 25050433
TI  - Longitudinal white matter changes in frontotemporal dementia subtypes.
AB  - Frontotemporal dementia is a degenerative brain condition characterized by focal
      atrophy affecting the frontal and temporal lobes predominantly. Changes in white
      matter with disease progression and their relationship to grey matter atrophy
      remain unknown in FTD. This study aimed to establish longitudinal white matter
      changes and compare these changes to regional grey matter atrophy in the main FTD
      subtypes. Diffusion and T1-weighted images were collected from behavioral-variant
      FTD (bvFTD: 12), progressive non-fluent aphasia (PNFA: 10), semantic dementia
      (SD: 11), and 15 controls at baseline and 12 months apart. Changes in white
      matter integrity were established by fractional anisotropy, mean, axial and
      radial diffusivity measurements using tract-based spatial statistics. Patterns of
      cortical grey matter atrophy were measured using voxel-based morphometry. At
      baseline, bvFTD showed severe cross-sectional changes in orbitofrontal and
      anterior temporal tracts, which progressed to involve posterior temporal and
      occipital white matter over the 12-month. In PNFA, cross-sectional changes
      occurred bilaterally in frontotemporal white matter (left > right), with
      longitudinal changes more prominent on the right. Initial white matter changes in
      SD were circumscribed to the left temporal lobe, with longitudinal changes
      extending to bilateral frontotemporal tracts. In contrast, progression of grey
      matter change over time was less pronounced in all FTD subtypes. Mean diffusivity
      was most sensitive in detecting baseline changes while fractional anisotropy and
      radial diffusivity revealed greatest changes over time, possibly reflecting
      different underlying pathological processes with disease progression. Our results
      indicate that investigations of white matter changes reveal important differences
      across FTD syndromes with disease progression.

PMID- 25050434
TI  - Sun exposure and longevity: a blunder involving immortal time.

PMID- 25050435
TI  - Serum levels of the soluble IL-1 receptor family member ST2 and right ventricular
      dysfunction.
AB  - AIMS: We aimed to assess the relationship between right ventricle (RV)
      dysfunction parameters and the soluble IL-1 receptor family member (sST2) in
      patients with secondary pulmonary hypertension owing tochronic obstructive
      pulmonary disease. MATERIALS & METHODS: A total of 36 patients with chronic
      obstructive pulmonary disease and secondary pulmonary hypertension (mean age: 59
      +/- 7 years) and 36 healthy volunteers (mean age: 59 +/- 8 years) were enrolled
      in the study. sST2 and NT-proBNP levels, as well as specific echocardiographic
      parameters were measured. RESULTS: Both sST2 and NT-proBNP levels were greater in
      the test group. The sST2 levels were inversely associated with RV fractional area
      change(r = -0.762; p < 0.001), as well as with the RV ejection fraction (r = 
      0.799; p < 0.001), tricuspid annular plane systolic excursion (r = -0.773; p <
      0.001) and increased pulmonary artery systolic pressure (r = 0.603;p < 0.001).
      Receiver operating characteristic curve analysis revealed that sST2 had lower
      sensitivity for identifying RV dysfunction when compared with NT-proBNP (71.4 vs
      100%), despite having the same specificity (84%). CONCLUSION: The current study
      reveals correlations between sST2 levels and echocardiographic parameters of RV
      dysfunction, suggesting that use of sST2 and NT-proBNP may improve diagnosis and
      risk stratification in patients with secondary pulmonary hypertension owing to
      chronic obstructive pulmonary disease.

PMID- 25050436
TI  - Optimization of rapid acquisition with relaxation enhancement (RARE) pulse
      sequence parameters for 19F-MRI studies.
AB  - PURPOSE: To optimize signal-to-noise ratio (SNR) in fast spin echo (rapid
      acquisition with relaxation enhancement [RARE]) sequences and to improve
      sensitivity in 19F magnetic resonance imaging (MRI) on a 7T preclinical MRI
      system, based on a previous experimental evaluation of T1 and T2 actual
      relaxation times. MATERIALS AND METHODS: Relative SNR changes were theoretically
      calculated at given relaxation times (T1, T2) and mapped in RARE parameter space
      (TR, number of echoes, flip back pulse), at fixed acquisition times. T1 and T2 of
      KPF6 phantom samples (solution, agar mixtures, ex vivo perfused brain) were
      measured and experimental SNR values were compared with simulations, at optimal
      and suboptimal RARE parameter values. RESULTS: The optimized setting largely
      depended on T1, T2 times and the use of flip back pulse improved SNR up to 30% in
      case of low T1/T2 ratios. Relaxation times in different conditions showed
      negligible changes in T1 (below 14%) and more evident changes in T2 (-95% from
      water solution to ex vivo brain). Experimental data confirmed theoretical
      forecasts, within an error margin always below 4.1% at SNR losses of ~20% and
      below 8.8% at SNR losses of ~40%. The optimized settings permitted a detection
      threshold at a concentration of 0.5 mM, corresponding to 6.22 * 1016 fluorine
      atoms per voxel. CONCLUSION: Optimal settings according to measured relaxation
      times can significantly improve the sensitivity threshold in 19F MRI studies.
      They were provided in a wide range of (T1, T2) values and experimentally
      validated showing good agreement.

PMID- 25050437
TI  - GAVI gears up for record replenishment.

PMID- 25050438
TI  - Under attack: Aleppo's hospitals.

PMID- 25050440
TI  - A tale of whistle-blowing and the English lunacy laws.

PMID- 25050439
TI  - An effective coarse-grained model for biological simulations: recent refinements
      and validations.
AB  - Exploring the free energy landscape of proteins and modeling the corresponding
      functional aspects presents a major challenge for computer simulation approaches.
      This challenge is due to the complexity of the landscape and the enormous
      computer time needed for converging simulations. The use of various simplified
      coarse grained (CG) models offers an effective way of sampling the landscape, but
      most current models are not expected to give a reliable description of protein
      stability and functional aspects. The main problem is associated with
      insufficient focus on the electrostatic features of the model. In this respect,
      our recent CG model offers significant advantage as it has been refined while
      focusing on its electrostatic free energy. Here we review the current state of
      our model, describing recent refinements, extensions, and validation studies
      while focusing on demonstrating key applications. These include studies of
      protein stability, extending the model to include membranes, electrolytes and
      electrodes, as well as studies of voltage-activated proteins, protein insertion
      through the translocon, the action of molecular motors, and even the coupling of
      the stalled ribosome and the translocon. The examples discussed here illustrate
      the general potential of our approach in overcoming major challenges in studies
      of structure function correlation in proteins and large macromolecular complexes.

PMID- 25050441
TI  - Ciro de Quadros.

PMID- 25050443
TI  - Structural basis of conformational variance in phosphorylated and non
      phosphorylated states of PKCbetaII.
AB  - PKCbetaII activation is achieved by primary phosphorylation at three
      phosphorylation sites, followed by the addition of secondary messengers for full
      activation. Phosphorylation is essential for enzyme maturation, and the
      associated conformational changes are known to modulate the enzyme activation. To
      probe into the structural basis of conformational changes on phosphorylation of
      PKCbetaII, a comprehensive study of the changes in its complexes with ATP and
      ruboxistaurin was performed. ATP is a phosphorylating agent in its
      phosphorylation reaction, and ruboxistaurin is its specific inhibitor. This study
      provides insight into the differences in the important structural features in
      phosphorylated and non-phosphorylated states of PKCbetaII. Less conformational
      changes when PKCbetaII is bound to inhibitor in comparison to when it is bound to
      its phosphorylating agent in both states were observed. The interactions of
      ruboxistaurin significant in restricting PKCbetaII to attain the conformational
      state competent for full activation are reported.

PMID- 25050442
TI  - The crystal structure of BlmI as a model for  nonribosomal peptide synthetase
      peptidyl  carrier proteins.
AB  - Carrier proteins (CPs) play a critical role in the biosynthesis of various
      natural products, especially in nonribosomal peptide synthetase (NRPS) and
      polyketide synthase (PKS) enzymology, where the CPs are referred to as peptidyl
      carrier proteins (PCPs) or acyl-carrier proteins (ACPs), respectively. CPs can
      either be a domain in large multifunctional polypeptides or standalone proteins,
      termed Type I and Type II, respectively. There have been many biochemical studies
      of the Type I PKS and NRPS CPs, and of Type II ACPs. However, recently a number
      of Type II PCPs have been found and biochemically characterized. In order to
      understand the possible interaction surfaces for combinatorial biosynthetic
      efforts we crystallized the first characterized and representative Type II PCP
      member, BlmI, from the bleomycin biosynthetic pathway from Streptomyces
      verticillus ATCC 15003. The structure is similar to CPs in general but most
      closely resembles PCPs. Comparisons with previously determined PCP structures in
      complex with catalytic domains reveals a common interaction surface. This surface
      is highly variable in charge and shape, which likely confers specificity for
      interactions. Previous nuclear magnetic resonance (NMR) analysis of a
      prototypical Type I PCP excised from the multimodular context revealed three
      conformational states. Comparison of the states with the structure of BlmI and
      other PCPs reveals that only one of the NMR states is found in other studies,
      suggesting the other two states may not be relevant. The state represented by the
      BlmI crystal structure can therefore serve as a model for both Type I and Type II
      PCPs.

PMID- 25050444
TI  - Biocompatibility of submicron Bioglass(r) powders obtained by a top-down
      approach.
AB  - In this study in vitro bioactivity and biocompatibility of two submicron 45S5
      Bioglass(r) powders obtained by topdown processing have been evaluated and are
      compared to the as-received powder. Both submicron powders exhibited flake-like
      morphologies with lateral extensions of only a few microns; the flake thickness
      accounted for a few tens of nanometers. Enhanced in vitro bioactivity was found
      for the comminuted powders upon immersion in simulated body fluid. In vitro
      biocompatibility was evaluated by incubation of MG-63 osteoblast-like cells with
      various amounts (0-200 MUg/mL) of the glass powders. Neither LDH-activity nor
      mitochondrial activity (WST-8) tests indicated cell toxicity. Increased
      mitochondrial activity was found for the submicron powders: incubation with high
      amounts revealed up to a threefold increase of osteoblast activity (ALP
      activity). An overgrowth of the formed mineralized phase with phenotypical MG-63
      cells was found by staining only for the submicron glasses. A distance ring is
      formed for the as-received powder. Superior bioactivity markers are found for
      shorter process times, that is, lower mass specific surface areas. This is
      attributed to the formation of carbonates during the comminution process.

PMID- 25050445
TI  - Hybrid photonic antennas for subnanometer multicolor localization and nanoimaging
      of single molecules.
AB  - Photonic antennas amplify and confine optical fields at the nanoscale offering
      excellent perspectives for nanoimaging and nanospectroscopy. Increased resolution
      beyond the diffraction limit has been demonstrated using a variety of antenna
      designs, but multicolor nanoscale imaging is precluded by their resonance
      behavior. Here we report on the design of a novel hybrid antenna probe based on a
      monopole nanoantenna engineered on a bowtie nanoaperture. The device combines
      broadband enhanced emission, extreme field confinement down to few nanometers,
      and zero-background illumination. We demonstrate simultaneous dual-color single
      molecule nanoimaging with 20 nm resolution and angstrom localization precision,
      corresponding to 10(3)-fold improvement compared to diffraction-limited optics.
      When interacting with individual molecules in the near-field, our innovative
      design enables the emission of 10(4) photon-counts per molecule in a 20 nm
      excitation region, allowing direct discrimination of spectrally distinct
      molecules separated by 2.1 +/- 0.4 nm. We foresee that background-free nanolight
      sources will open new horizons in optical nanoscopy and fluorescence spectroscopy
      by providing multicolor detection of standard fluorescent molecules fully
      compatible with live cell research. 

PMID- 25050447
TI  - Differentiating organically and conventionally grown oregano using
      ultraperformance liquid chromatography mass spectrometry (UPLC-MS), headspace gas
      chromatography with flame ionization detection (headspace-GC-FID), and flow
      injection mass spectrum (FIMS) fingerprints combined with multivariate data
      analysis.
AB  - Ultraperformance liquid chromatography mass spectrometry (UPLC-MS), flow
      injection mass spectrometry (FIMS), and headspace gas chromatography (headspace
      GC) combined with multivariate data analysis techniques were examined and
      compared in differentiating organically grown oregano from that grown
      conventionally. It is the first time that headspace-GC fingerprinting technology
      is reported in differentiating organically and conventionally grown spice
      samples. The results also indicated that UPLC-MS, FIMS, and headspace-GC-FID
      fingerprints with OPLS-DA were able to effectively distinguish oreganos under
      different growing conditions, whereas with PCA, only FIMS fingerprint could
      differentiate the organically and conventionally grown oregano samples. UPLC
      fingerprinting provided detailed information about the chemical composition of
      oregano with a longer analysis time, whereas FIMS finished a sample analysis
      within 1 min. On the other hand, headspace GC-FID fingerprinting required no
      sample pretreatment, suggesting its potential as a high-throughput method in
      distinguishing organically and conventionally grown oregano samples. In addition,
      chemical components in oregano were identified by their molecular weight using
      QTOF-MS and headspace-GC-MS. 

PMID- 25050446
TI  - A systematic review of the safety and efficacy of mesenchymal stem cells for disc
      degeneration: insights and future directions for regenerative therapeutics.
AB  - Intervertebral disc degeneration is associated with low-back pain. Mesenchymal
      stem cells (MSCs) have been used to "regenerate" the disc. The aim of this study
      was to perform a systematic review of comparative controlled studies that have
      assessed the safety and efficacy of using MSCs for disc regeneration. Literature
      databases were extensively searched. Trial design, subject-type, MSC sources,
      injection method, disc assessment, outcome intervals, and complication events
      were assessed. Validity of each study was performed. Twenty-four animal studies
      were included with 20.8% of the studies reporting randomization of groups. Trials
      in humans fulfilling inclusion criteria were not noted. The studies represented
      862 discs that were injected with MSCs and 1,603 discs as controls. All three
      types of MSCs (ie, bone marrow, synovial, and adipose tissues) showed successful
      inhibition of disc degeneration. Bone-marrow-derived MSCs demonstrated superior
      quality of repair compared with other non-MSC treatments. A 2.7% overall
      complication rate was noted, whereby complications were noted only in rabbits.
      Overall, evidence suggested that MSCs increased disc space height in the majority
      of animal models. This is the first systematic review to assess the safety and
      efficacy of MSCs for the treatment of disc degeneration. Short-term MSC
      transplantation is safe and effective; however, additional, larger, and higher
      quality studies are needed to assess the long-term safety and efficacy.
      Inconsistencies in methodological design and outcome parameters prevent any
      robust conclusions. Human-based clinical trials are needed. Recommendations are
      further made to improve efficacy, reduce potential complications, and standardize
      techniques for future studies. 

PMID- 25050448
TI  - Polarization-modulated second harmonic generation ellipsometric microscopy at
      video rate.
AB  - Fast 8 MHz polarization modulation coupled with analytical modeling, fast beam
      scanning, and synchronous digitization (SD) have enabled simultaneous nonlinear
      optical Stokes ellipsometry (NOSE) and polarized laser transmittance imaging with
      image acquisition rates up to video rate. In contrast to polarimetry, in which
      the polarization state of the exiting beam is recorded, NOSE enables recovery of
      the complex-valued Jones tensor of the sample that describes all polarization
      dependent observables of the measurement. Every video-rate scan produces a set of
      30 images (10 for each detector with three detectors operating in parallel), each
      of which corresponds to a different polarization-dependent result. Linear fitting
      of this image set contracts it down to a set of five parameters for each detector
      in second harmonic generation (SHG) and three parameters for the transmittance of
      the incident beam. These parameters can in turn be used to recover the Jones
      tensor elements of the sample. Following validation of the approach using z-cut
      quartz, NOSE microscopy was performed for microcrystals of both naproxen and
      glucose isomerase. When weighted by the measurement time, NOSE microscopy was
      found to provide a substantial (>7 decades) improvement in the signal-to-noise
      ratio relative to our previous measurements based on the rotation of optical
      elements and a 3-fold improvement relative to previous single-point NOSE
      approaches. 

PMID- 25050449
TI  - Dewetting film dynamics inside a capillary using a micellar nanofluid.
AB  - An experimental study was performed in which hexadecane was displaced by a
      micellar nanofluid in a glass capillary. Experiments have shown that a thick film
      was formed on the capillary wall after hexadecane was displaced by the nanofluid.
      The thick hexadecane film is unstable, and over time it breaks and forms a thin
      film. Once the thick film ruptures, it retracts and forms an annular rim (liquid
      ridge) that collects liquid. As the volume of the annular rim increases over
      time, it forms a double-concave meniscus across the capillary and dewetting
      stops. The thin film on the right side of the double-concave meniscus then breaks
      and the contact angle increases. The process repeats until the droplets build up
      all along the capillary wall. Finally, the droplets are displaced from the
      capillary wall by the nanofluid and spherical droplets appear inside the
      capillary. This is a novel phenomenon because we did not observe any film
      formation when we used a solution without micelles. The theoretical model based
      on the lubrication approximation using the capillary pressure gradient was
      developed to estimate the annular rim dewetting velocity. The predicted dewetting
      velocity is found to be in fair agreement with the experimentally measured value.

PMID- 25050450
TI  - Could a traumatic epidural hematoma on early computed tomography tell us about
      its future development? A multi-center retrospective study in China.
AB  - Our aim for this study was to quantitatively develop an early epidural hematoma
      (EDH) natural evolutionary curve and assess association of the most common
      radiological signs of initially nonsurgical supratentorial EDHs on early computed
      tomography (CT), in addition to their CT time for EDH enlargement. We
      retrospectively reviewed pertinent data of supratentorial EDH cases with CT <= 6
      h postinjury (1997-2013) in three medical institutions in Shanghai. Cases
      involved were divided into six groups according to their initial CT time
      postinjury (<= 1, 1-2, 2-3, 3-4, 4-5, and 5-6 h for groups 1 through 6,
      respectively). Time of initial CT, EDH-associated fractures, EDH volume, and EDH
      locations were the focus in the present study. A total of 797 eligible cases were
      included. The EDH growth curve showed that EDH reached 98.1% of its final
      stabilized size by volume in 5 ~ 6 h postinjury. EDH volume and locations on
      initial CT was greatly associated with subsequent EDH increase >= 30 mL with EDH
      increase requiring surgery when CT time was added. Multi-variate analysis
      succeeded in determining two risk factors for EDH enlargement >= 30 mL and EDH
      enlargement requiring an operation for EDH cases with an early CT/EDH volume >10
      mL on CT performed <= 2 h and EDH located at the temporal or temporoparietal
      region on CT <= 1 h post brain injury. Using recursive partitioning analysis,
      "high-risk" identification criteria were derived to predict EDH enlargement >= 30
      mL with sensitivity of 90.5% (95% confidence interval [CI], 77.9-96.2),
      specificity of 60.1% (95% CI, 54.3-65.7), and EDH enlargement requiring surgery
      with sensitivity of 100.0% (95% CI, 89.9-100.0), and specificity of 59.9% (95%
      CI, 54.1-65.4). A redo-CT 5 ~ 6 h post impact for cases at high risk is
      recommended.

PMID- 25050451
TI  - Proteome phenotyping of DeltarelA mutants in Enterococcus faecalis V583.
AB  - The (p)ppGpp synthetase RelA contributes to stress adaptation and virulence in
      Enterococcus faecalis V583. A 2-dimensional electrophoresis proteomic analysis of
      2 relA mutants, i.e., DeltarelA carrying a complete deletion of the relA gene,
      and DeltarelAsp that is deleted from only its 3' extremity, showed that 31
      proteins were deregulated in 1 or both of these mutants. Mass spectrometry
      identification of these proteins showed that 10 are related to translation,
      including 5 ribosomal proteins, 3 proteins involved in translation elongation,
      and 2 proteins in tRNA synthesis; 14 proteins are involved in diverse metabolisms
      and biosynthesis (8 in sugar and energy metabolisms, 2 in fatty acid
      biosynthesis, 2 in amino acid biosynthesis, and 2 in nucleotide metabolism). Five
      proteins were relevant to the adaptation to different environmental stresses,
      i.e., SodA and a Dps family protein, 2 cold-shock domain proteins, and Ef1744,
      which is a general stress protein that plays an important role in the response to
      ethanol stress. The potential role of these proteins in the development of stress
      phenotypes associated with these mutations is discussed. 

PMID- 25050452
TI  - Effect of C5-methylation of cytosine on the photoreactivity of DNA: a joint
      experimental and computational study of TCG trinucleotides.
AB  - DNA methylation, occurring at the 5 position of cytosine, is a natural process
      associated with mutational hotspots in skin tumors. By combining experimental
      techniques (optical spectroscopy, HPLC coupled to mass spectrometry) with
      theoretical methods (molecular dynamics, DFT/TD-DFT calculations in solution), we
      study trinucleotides with key sequences (TCG/T5mCG) in the UV-induced DNA damage.
      We show how the extra methyl, affecting the conformational equilibria and, hence,
      the electronic excited states, increases the quantum yield for the formation of
      cyclobutane dimers while reducing that of (6-4) adducts. 

PMID- 25050453
TI  - Augmenting antidepressants with deep transcranial magnetic stimulation (DTMS) in
      treatment-resistant major depression.
AB  - OBJECTIVES: Deep transcranial magnetic stimulation (DTMS) has been shown to be
      efficacious and relatively safe for major depressive disorder (MDD). However, its
      clinical utility as an augmenting strategy for treatment-resistant depression
      (TRD) remains unexplored. METHODS: In an open label trial, 17 outpatients with
      severe TRD received 4 weeks of daily high frequency DTMS over the left
      dorsolateral prefrontal cortex. Depressive and anxious symptoms, suicidality and
      quality of life (QOL) were measured at baseline (i.e., in the week prior to the
      start of the DTMS treatment) and at week 5 (i.e., in the week following the end
      of the DTMS treatment). Primary outcome measures were rates of response and
      remission at week 5 using an intention-to-treat approach. RESULTS: Response and
      remission rates at week 5 were 70.6 and 41.2%, respectively. Also, depression,
      anxiety, and suicidality ratings were significantly improved by week 5 (with
      Hedges' g estimates ranging from 0.6 to 1.72), as well as four of the five QOL
      domain scores (i.e., global, psychological, environmental and social). Finally,
      two patients dropped out of the study at week 1 because of significant scalp
      discomfort during stimulation. CONCLUSIONS: Our study suggests that DTMS, when
      used as an augmenting strategy for antidepressants in severe TRD, is efficacious,
      safe and relatively well tolerated. However, controlled studies with larger
      samples are needed to confirm and expand our preliminary findings.

PMID- 25050454
TI  - Formation of liquid-crystalline structures in the bile salt-chitosan system and
      triggered release from lamellar phase bile salt-chitosan capsules.
AB  - Nanostructured capsules comprised of the anionic bile salt, sodium
      taurodeoxycholate (STDC), and the biocompatible cationic polymer, chitosan, were
      prepared to assess their potential as novel tailored release nanomaterials. For
      comparison, a previously studied system, sodium dodecyl sulfate (SDS), and
      polydiallyldimethylammonium chloride (polyDADMAC) was also investigated. Crossed
      polarizing light microscopy (CPLM) and small-angle X-ray scattering (SAXS)
      identified the presence of lamellar and hexagonal phase at the surfactant-polymer
      interface of the respective systems. The hydrophobic and electrostatic
      interactions between the oppositely charged components were studied by varying
      temperature and salt concentration, respectively, and were found to influence the
      liquid-crystalline nanostructure formed. The hexagonal phase persisted at high
      temperatures, however the lamellar phase structure was lost above ca. 45  degrees
      C. Both mesophases were found to dissociate upon addition of 4% NaCl solution.
      The rate of release of the model hydrophilic drug, Rhodamine B (RhB), from the
      lamellar phase significantly increased in response to changes in the solution
      conditions studied, suggesting that modulating the drug release from these bile
      salt-chitosan capsules is readily achieved. In contrast, release from the
      hexagonal phase capsules had no appreciable response to the stimuli applied.
      These findings provide a platform for these oppositely charged surfactant and
      polymer systems to function as stimuli-responsive or sustained-release drug
      delivery systems. 

PMID- 25050455
TI  - Alloyed copper chalcogenide nanoplatelets via partial cation exchange reactions.
AB  - We report the synthesis of alloyed quaternary and quinary nanocrystals based on
      copper chalcogenides, namely, copper zinc selenide-sulfide (CZSeS), copper tin
      selenide-sulfide (CTSeS), and copper zinc tin selenide-sulfide (CZTSeS)
      nanoplatelets (NPLs) (~20 nm wide) with tunable chemical composition. Our
      synthesis scheme consisted of two facile steps: i.e., the preparation of copper
      selenide-sulfide (Cu2-xSeyS1-y) platelet shaped nanocrystals via the colloidal
      route, followed by an in situ cation exchange reaction. During the latter step,
      the cation exchange proceeded through a partial replacement of copper ions by
      zinc or/and tin cations, yielding homogeneously alloyed nanocrystals with
      platelet shape. Overall, the chemical composition of the alloyed nanocrystals can
      easily be controlled by the amount of precursors that contain cations of interest
      (e.g., Zn, Sn) to be incorporated/alloyed. We have also optimized the reaction
      conditions that allow a complete preservation of the size, morphology, and
      crystal structure as that of the starting Cu2-xSeyS1-y NPLs. The alloyed NPLs
      were characterized by optical spectroscopy (UV-vis-NIR) and cyclic voltammetry
      (CV), which demonstrated tunability of their light absorption characteristics as
      well as their electrochemical band gaps. 

PMID- 25050456
TI  - Safety and pharmacokinetics of ciprofloxacin dry powder for inhalation in cystic
      fibrosis: a phase I, randomized, single-dose, dose-escalation study.
AB  - BACKGROUND: Reliable, reproducible deposition to the lung is a major prerequisite
      for the clinical use of inhaled drugs. Ciprofloxacin dry powder for inhalation
      (ciprofloxacin DPI; Bayer HealthCare AG, Leverkusen, Germany) is an antibacterial
      therapy in development using Novartis' PulmoSphereTM technology (Novartis Pharma
      AG, Basel, Switzerland) for the targeted delivery of ciprofloxacin to the lung
      via a T-326 inhaler. METHODS: This randomized, single-blind, placebo-controlled,
      dose-escalation study investigated the safety, tolerability, and pharmacokinetics
      of single-dose ciprofloxacin DPI (32.5 mg [n=6] or 65 mg [n=6]) and matching
      placebo (n=4) in adult patients with cystic fibrosis and stable pulmonary status
      (forced expiratory volume in 1 sec >=30%) who were colonized with Pseudomonas
      aeruginosa. RESULTS: Peak sputum concentrations of 34.9 mg/L (range 2.03-229) and
      376 mg/L (8.95-1283) for ciprofloxacin 32.5 mg and 65 mg, respectively, indicated
      targeting of ciprofloxacin DPI to the lung. This contrasted with low systemic
      exposure (peak plasma concentrations: 0.0790 mg/L [32.5 mg] and 0.182 mg/L [65
      mg]). Single-dose ciprofloxacin DPI 32.5 mg or 65 mg was well tolerated with
      similar incidences of adverse events across all groups. No deaths,
      discontinuations, treatment-related serious adverse events, or clinically
      relevant changes in laboratory parameters, vital signs, or lung function tests
      were reported. CONCLUSIONS: Lung targeting with high pulmonary concentrations of
      ciprofloxacin combined with low systemic exposure was confirmed. These results
      support further study of ciprofloxacin DPI as a potentially more convenient
      alternative to nebulized antibiotic solutions for managing chronic lung
      infections.

PMID- 25050457
TI  - Presentation and initial assessment of ENT problems in patients with
      granulomatosis with polyangiitis (Wegener's).
AB  - BACKGROUND: Granulomatosis with polyangiitis (formerly known as Wegener's
      granulomatosis) is a primary systemic vasculitis that affects medium to small
      sized vessels throughout the body. It often presents with symptoms and signs
      involving the ear, nose, and head and neck area. OBJECTIVE: To highlight salient
      features of ENT-related issues in granulomatosis with polyangiitis, and raise
      awareness of the condition. METHODS: A case report of a patient with limited
      disease and an insidious onset is presented, along with a review of the current
      literature. In addition, basic initial management is described. RESULTS: Eighty
      six publications were used to describe salient features of ENT-related issues in
      granulomatosis with polyangiitis. CONCLUSION: The time to diagnosis has not
      reduced significantly in the last 10 years in the UK. A high index of suspicion
      is required for an earlier diagnosis of granulomatosis with polyangiitis.

PMID- 25050458
TI  - Release of Pu isotopes from the Fukushima Daiichi Nuclear Power Plant accident to
      the marine environment was negligible.
AB  - Atmospheric deposition of Pu isotopes from the Fukushima Daiichi Nuclear Power
      Plant (FDNPP) accident has been observed in the terrestrial environment around
      the FDNPP site; however, their deposition in the marine environment has not been
      studied. The possible contamination of Pu in the marine environment has attracted
      great scientific and public concern. To fully understand this possible
      contamination of Pu isotopes from the FDNPP accident to the marine environment,
      we collected marine sediment core samples within the 30 km zone around the FDNPP
      site in the western North Pacific about two years after the accident. Pu isotopes
      ((239)Pu, (240)Pu, and (241)Pu) and radiocesium isotopes ((134)Cs and (137)Cs) in
      the samples were determined. The high activities of radiocesium and the
      (134)Cs/(137)Cs activity ratios with values around 1 (decay corrected to 15 March
      2011) suggested that these samples were contaminated by the FDNPP accident
      released radionuclides. However, the activities of (239+240)Pu and (241)Pu were
      low compared with the background level before the FDNPP accident. The Pu atom
      ratios ((240)Pu/(239)Pu and (241)Pu/(239)Pu) suggested that global fallout and
      the pacific proving ground (PPG) close-in fallout are the main sources for Pu
      contamination in the marine sediments. As Pu isotopes are particle-reactive and
      they can be easily incorporated with the marine sediments, we concluded that the
      release of Pu isotopes from the FDNPP accident to the marine environment was
      negligible. 

PMID- 25050459
TI  - Lipophilic contaminants influence cold tolerance of invertebrates through changes
      in cell membrane fluidity.
AB  - Contaminants taken up by living organisms in the environment as a result of
      anthropogenic contamination can reduce the tolerance of natural stressors, e.g.,
      low temperatures, but the physiological mechanisms behind these interactions of
      effects are poorly understood. The tolerance to low temperatures of organisms
      that cannot regulate their body temperature (ectotherms) depends on their ability
      to increase the fluidity of their cellular membranes at low temperatures. Our
      study shows that contaminants accumulating in lipids of organisms alter the
      physical state of their membranes simply by being present. Contaminants of
      varying chemical structures can alter the membrane fluidity in either direction
      and correspondingly modulate the cold tolerance of intact animals. 

PMID- 25050460
TI  - Expression, solubilisation, and purification of a functional CMP-sialic acid
      transporter in Pichia pastoris.
AB  - Membrane proteins, including solute transporters play crucial roles in cellular
      function and have been implicated in a variety of important diseases, and as such
      are considered important targets for drug development. Currently the drug
      discovery process is heavily reliant on the structural and functional information
      discerned from high-resolution crystal structures. However, membrane protein
      structure determination is notoriously difficult, due in part to challenges faced
      in their expression, solubilisation and purification. The CMP-sialic acid
      transporter (CST) is considered to be an attractive target for drug discovery.
      CST inhibition reduces cancer cell sialylation and decreases the metastatic
      potential of cancer cells and to date, no crystal structure of the CST, or any
      other nucleotide sugar transporter exists. Here we describe the optimised
      conditions for expression in Pichia pastoris, solubilisation using n-nonyl beta-d
      maltopyranoside (NM) and single step purification of a functional CST.
      Importantly we show that despite being able to solubilise and purify the CST
      using a number of different detergents, only NM was able to maintain CST
      functionality.

PMID- 25050461
TI  - Bacterial expression of the HINab domain of IFI16: purification, characterization
      of DNA binding activity, and co-crystallization with viral dsDNA.
AB  - Interferon-inducible protein 16 (IFI16) is a multifunctional p200-family protein
      that plays pivotal roles in p53-mediated apoptosis, tumor suppression and DNA
      damage response. Recently, another function of IFI16 in innate immune sensing and
      response has been uncovered, in which IFI16 recognizes the exogenous DNAs through
      cooperative binding of DNAs via its two DNA binding domains, HINa and HINb.
      Although the mechanism by which the HINb domain recognizes DNAs has been
      elucidated, the molecular basis of the cooperativity between HINa and HINb during
      DNA recognition process is still not clear. Here we report expression and
      purification of a truncated human IFI16 protein (HINab-GS) containing HINa in
      tandem with HINb with the joining region between HINa and HINb replaced by a
      short GS linker in Escherichia coli. DNA binding activities of HINab-GS to
      various double-stranded DNAs (dsDNAs) of different lengths were then examined
      using electrophoretic mobility shift assays. HINab-GS exhibited efficient binding
      activity to dsDNAs, and its DNA binding affinity correlated positively with the
      length of dsDNAs. A co-crystallization condition of HINab-GS bound to a 30 bp
      dsDNA derived from vaccinia virus was also found. Together, our work provides a
      basis for structurally elucidating the mechanism governing cooperative DNA
      recognition by IFI16.

PMID- 25050463
TI  - Gambogic Acid and inhibition of tumor growth: a close association.

PMID- 25050462
TI  - A scalable method for biochemical purification of Salmonella flagellin.
AB  - Flagellins are the main structural proteins of bacterial flagella and potent
      stimulators of innate and adaptive immunity in mammals. The flagellins of
      Salmonella are virulence factors and protective antigens, and form the basis of
      promising vaccines. Despite broad interest in flagellins as antigens and
      adjuvants in vaccine formulations, there have been few advances towards the
      development of scalable and economical purification methods for these proteins.
      We report here a simple and robust strategy to purify flagellin monomers from the
      supernatants of liquid growth culture. Phase 1 flagellins from Salmonella
      enterica serovars Typhimurium (i epitope) and Enteritidis (g,m epitopes) were
      purified directly from conditioned fermentation growth media using sequential
      cation- and anion-exchange chromatography coupled with a final tangential flow
      filtration step. Conventional porous chromatography resin was markedly less
      efficient than membrane chromatography for flagellin purification. Recovery after
      each process step was robust, with endotoxin, nucleic acid and residual host-cell
      protein effectively removed. The final yield was 200-300 mg/L fermentation
      culture supernatant, with ~45-50% overall recovery. A final pH 2 treatment step
      was instituted to ensure uniformity of flagellin in the monomeric form.
      Flagellins purified by this method were recognized by monoclonal anti-flagellin
      antibodies and maintained capacity to activate Toll-like Receptor 5. The process
      described is simple, readily scalable, uses standard bioprocess methods, and
      requires only a few steps to obtain highly purified material.

PMID- 25050464
TI  - Neural tissue engineering scaffold with sustained RAPA release relieves
      neuropathic pain in rats.
AB  - AIMS: To investigate the effect of locally slow-released rapamycin (RAPA) from
      bionic peripheral nerve stent to reduce the incidence of neuropathic pain or
      mitigate the degree of pain after nerve injury. MAIN METHODS: We constructed a
      neural tissue engineering scaffold with sustained release of RAPA to repair 20mm
      defects in rat sciatic nerves. Four presurgical and postsurgical time windows
      were selected to monitor the changes in the expression of pain-related dorsal
      root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and
      1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the
      observation of postsurgical pathological pain in rats by pain-related behavior
      approaches. KEY FINDINGS: Relatively small upregulation of DRG sodium channels
      was observed in the experimental group (RAPA+poly(lactic-co-glycolic acid)
      (PLGA)+stent) after surgery, along with low degrees of neuropathic pain and
      anxiety, which were similar to those in the Autologous nerve graft group.
      SIGNIFICANCE: Autoimmune inflammatory response plays a leading role in the
      occurrence of post-traumatic neuropathic pain, and that RAPA significantly
      inhibits the abnormal upregulation of sodium channels to reduce pain by
      alleviating inflammatory response.

PMID- 25050465
TI  - First trimester vitamin D status and placental epigenomics in preeclampsia among
      Northern Plains primiparas.
AB  - AIMS: As maternal vitamin D status has been associated with preeclampsia, the
      purpose of this study was to determine variations in DNA methylation patterns and
      associated protein expression in placental genes regulating vitamin D metabolism.
      MAIN METHODS: A convenience sample of 48 pregnant nulliparous women, including 11
      later diagnosed with preeclampsia, were recruited in this prospective study.
      Using a case-control design in two groups of women, we administered a food
      frequency questionnaire to determine vitamin D dietary intake. Laboratory
      measures included serum vitamin D levels (25[OH]D), DNA methylation patterns and
      protein expression in placental genes regulating vitamin D metabolism (1alpha
      hydroxylase, CYP27B1; vitamin D receptor, VDR; retinoid X receptor, RXR) from
      placental tissue collected at delivery among those diagnosed with preeclampsia
      and those who remained normotensive throughout pregnancy. KEY FINDINGS: There
      were no significant differences in vitamin D dietary intake or mean serum 25[OH]D
      levels, although the proportion of women with deficient 25[OH]D levels was higher
      in the preeclampsia group (46%) than the normotensive group (20%). Placenta
      samples from women with preeclampsia also had increased DNA methylation of
      CYP27B1, VDR and RXR genes with lower protein expression levels limited to RXR.
      SIGNIFICANCE: Hypermethylation of key placental genes involved in vitamin D
      metabolism suggests uncoupling of processes that may interfere with placentation
      and availability of vitamin D at the maternal-fetal interface.

PMID- 25050466
TI  - Annulated isoxazoles via [3 + 2] cycloaddition of alkenyl bromides and oximoyl
      chlorides and Ag(I) promoted elimination.
AB  - Substituted salicylaldehydes are converted to fused tetracyclic isoxazoles
      through a synthetic sequence incorporating substitution of 2-bromo-2-cyclohexen-1
      ol, formation of an oxime function, conversion to an oximoyl chloride,
      intramolecular [3 + 2] cycloaddition, and elimination of an equivalent of
      hydrogen bromide using silver(I) carbonate. Six examples of this sequence are
      presented. 

PMID- 25050467
TI  - Recent advances in the study of somatic mosaicism and diseases other than cancer.
AB  - Somatic mosaicism is well appreciated as a cause of cancer and, possibly, aging.
      Somatic mosaicism as the cause of other diseases is becoming more appreciated. It
      is especially important in the causation of deforming diseases (e.g., Proteus
      syndrome; Sturge-Weber syndrome) which are not inherited because early
      developmental expression is lethal. It also known to make an important
      contribution to neurological, dermatological, hematological and other diseases
      (and probably all diseases but many in which it is harder to detect). There have
      been exciting recent advances in the detection of somatic mosaicism. In
      particular, for many diseases of somatic overgrowth in which somatic mosaicism as
      the sole cause was predicted, the gene somatically mutated has been found. A
      limited number of pathways seem involved in these disorders, some of which are
      also implicated in cancer. 

PMID- 25050469
TI  - Serum hypoalbuminemia predicts late mortality on the liver transplant waiting
      list.
AB  - BACKGROUND: The reduction of liver transplant wait list mortality remains a
      priority for transplant programs and depends on the accurate stratification of
      patients by mortality risk. Although estimation of 90-day mortality by Model for
      End-Stage Liver Disease (MELD) score has improved wait list survival, it is
      unclear how contemporary wait list mortality can best be diminished given the
      preponderance of listed patients with low MELD scores and long wait times.
      METHODS: In this intention-to-treat analysis of 289 consecutively listed patients
      with over 5 years of follow-up, we aimed to determine the contribution of late
      mortality to overall wait list outcome and identify clinical predictors that
      would help discriminate long-term survivors from fatalities. RESULTS: Seventy
      percent of wait list deaths occurred in patients listed with MELD scores less
      than 20, and 40% of deaths occurred in patients waiting longer than 1 year.
      Hypoalbuminemia at listing was a significant predictor of late mortality in all
      patients in both univariate and multivariate analyses, and it was most
      discriminatory among patients with MELD scores of 20 or less. CONCLUSION: Our
      data suggest that hypoalbuminemia at listing reveals a vulnerable population of
      low MELD patients who are underserved by their MELD score over time. Such
      patients comprise almost 40% of the contemporary wait list and contribute
      substantially to list mortality given their poor access to transplantation.
      Targeting these at-risk patients with grafts from living or extended criteria
      donors may thus significantly diminish overall list mortality, and future
      initiatives to decrease overall wait list mortality must focus on improved risk
      stratification for low MELD patients.

PMID- 25050468
TI  - Induction of cytomegalovirus-specific T cell responses in healthy volunteers and
      allogeneic stem cell recipients using vaccination with messenger RNA-transfected
      dendritic cells.
AB  - BACKGROUND: Infection with human cytomegalovirus (CMV) is a significant cause of
      morbidity and mortality in solid organ and hematopoietic stem cell transplant
      (HSCT) recipients. METHODS: The present study explored the safety, feasibility,
      and immunogenicity of CMV pp65 messenger RNA-loaded autologous monocyte-derived
      dendritic cells (DC) as a cellular vaccine for active immunization in healthy
      volunteers and allogeneic HSCT recipients. Four CMV-seronegative healthy
      volunteers and three allogeneic HSCT recipients were included in the study. Four
      clinical-grade autologous monocyte-derived DC vaccines were prepared after a
      single leukapheresis procedure and administered intradermally at a weekly
      interval. RESULTS: De novo induction of CMV-specific T-cell responses was
      detected in three of four healthy volunteers without serious adverse events. Of
      the HSCT recipients, none developed CMV disease and one of two patients displayed
      a remarkable threefold increase in CMV pp65-specific T cells on completion of the
      DC vaccination trial. CONCLUSION: In conclusion, our DC vaccination strategy
      induced or expanded a CMV-specific cellular response in four of six efficacy
      evaluable study subjects, providing a base for its further exploration in larger
      cohorts.

PMID- 25050470
TI  - Laparoscopic living donor nephrectomy: making optimal use of donors without doing
      harm.

PMID- 25050471
TI  - Three-year outcomes following 1420 ABO-incompatible living-donor kidney
      transplants performed after ABO antibody reduction: results from 101 centers.
AB  - BACKGROUND: Reports from experienced centers suggest that recipients of an ABO
      incompatible living-donor kidney transplant after reduction of ABO antibodies
      experience no penalty in graft and patient survival versus ABO-compatible
      transplants, but confirmation that these results can be widely replicated is
      lacking. METHODS: Living-donor kidney transplants from ABO-incompatible donors
      after ABO antibody reduction registered with the Collaborative Transplant Study
      during 2005 to 2012 were analyzed and compared with (i) a matched group of ABO
      compatible transplant recipients and (ii) all ABO-compatible transplants from
      centers that performed at least five ABO-incompatible grafts during the study
      period. RESULTS: One thousand four hundred twenty living-donor ABO-incompatible
      kidney transplants were analyzed. Three-year death-censored graft survival was
      virtually identical for ABO-incompatible transplants versus matched and center
      controls (P=0.92 and P=0.60, respectively). Patient survival rates were also
      similar (P=0.15 and P=0.11, respectively). Early patient survival was lower in
      ABO-incompatible grafts (P=0.006 vs. matched controls; P=0.001 vs. center
      controls) because of a higher rate of early infectious death (P=0.037 and
      P<0.001, respectively). Death-censored graft and patient survival were not
      significantly affected by induction therapy and anti-CD20 treatment. ABO antibody
      reduction by column adsorption was associated with similar death-censored graft
      survival to plasmapheresis. CONCLUSION: In this analysis of prospectively
      collected data from a large series of ABO-incompatible living-donor kidney
      transplants performed at 101 centers, death-censored graft and patient survival
      rates were similar to those achieved in ABO-compatible control groups over the
      same period.

PMID- 25050472
TI  - Long-term changes in bone mineral density in kidney transplant recipients.
AB  - BACKGROUND: Alterations in bone mineral metabolism occur when kidney function
      declines and often continue after transplantation. We investigated long-term
      changes in bone mineral density (BMD) among kidney transplant recipients
      undergoing routine clinical BMD monitoring and management. METHODS: We identified
      adults receiving a kidney transplant in the province of Manitoba, Canada (1996
      2011) who had greater than or equal to 2 posttransplant dual energy X-ray
      absorptiometry examinations. Bone mineral density was expressed as Z scores
      (standard deviation above/below sex-matched and age-matched reference data). The
      main outcome was the change in BMD. RESULTS: A total of 326 kidney transplant
      recipients were included (mean age, 45 years; 61% men). Recipients were followed
      up for an average of 8.2 years (766 follow-up dual energy X-ray absorptiometry
      measurements). At baseline (first scan; median, 0.5 years after transplantation),
      bone density was slightly below average for age and sex (mean Z scores: lumbar
      spine, -0.4 +/- 1.6; femoral neck, -0.7 +/- 1.1; total hip, -0.7 +/- 1.1). At the
      second scan (mean, 2.7 years after first scan), mean bone density Z scores have
      increased (lumbar spine, -0.2 +/- 1.6; femoral neck, -0.6 +/- 1; total hip, -0.6
      +/- 1.1; matched, P < 0.01 at all sites). The only factor associated with a
      significant BMD change at all sites was osteoporosis treatment (BMD increase).
      Even after restricting the analysis to recipients who had not received
      osteoporosis treatment, final mean bone density (mean, 8.2 years after first
      scan) was average for age and sex (lumbar spine, +0.7 +/- 1.6; femoral neck, -0.1
      +/- 1.1; total hip, 0.0 +/- 1.1). CONCLUSION: With routine BMD monitoring and
      management, posttransplant bone density typically remains stable or improves with
      mean values that are average for age and sex.

PMID- 25050473
TI  - Differential cytokine, chemokine and growth factor expression in phenotypes of
      chronic lung allograft dysfunction.
AB  - BACKGROUND: Chronic lung allograft dysfunction is a heterogeneous entity limiting
      long-term survival after lung transplantation. Different clinical phenotypes
      (bronchiolitis obliterans syndrome [BOS]-neutrophilic BOS-restrictive allograft
      syndrome [RAS]) have been identified but the mechanisms remain elusive. METHODS:
      In this study, we measured 34 different cytokines, chemokines, and growth factors
      in bronchoalveolar lavage fluid of 20 stable patients, 20 patients suffering from
      non-neutrophilic BOS, 17 from neutrophilic BOS, and 20 from RAS using classic
      enzyme-linked immunosorbent assay and multiplex technology. RESULTS: Total cell
      count and % neutrophils were elevated in neutrophilic BOS and RAS compared to
      stable and non-neutrophilic BOS patients, whereas also the % eosinophils was
      elevated at diagnosis of RAS. Levels of interleukin (IL)-1beta (P<0.01), IL
      1Ralpha (P<0.001), IL-6 (P<0.001), IL-8/CXCL8 (P<0.001), IP-10/CXCL10 (P<0.05),
      MCP-1/CCL2 (P<0.05), macrophage inflammatory protein (MIP)-1alpha/CCL3 (P<0.001),
      MIP-1beta/CCL4, and vascular endothelial growth factor (VEGF; P<0.05) were
      differentially regulated in RAS compared to stable, whereas in neutrophilic BOS
      IL-1beta (P<0.001), IL-1Ralpha (P<0.01), IL-7 (P<0.05), IL-8/CXCL8 (P<0.001), MCP
      3/CXCCL7 (P<0.05) and MIP-1alpha/CCL-3 (P<0.05) were significantly upregulated
      compared to stable patients. We could not detect any differences between non
      neutrophilic BOS and stable patients. Interestingly, bronchoalveolar lavage IL-6,
      interferon gamma-induced protein (IP)-10/CXCL10 and interferon-inducible T-cell
      alpha chemoattractant/chemokine (C-X-C motif) ligand 11 (ITAC/CXCL10) were
      associated with survival after diagnosis in RAS patients. CONCLUSION: There were
      major differences in cytokine and chemokine expression in our different study
      groups. Especially IL-6, but also IP-10/CXCL10, and VEGF may be interesting
      mediators in RAS.

PMID- 25050474
TI  - Sound-induced hyperpolarization of hippocampal neurons.
AB  - The hippocampus is involved in episodic memory, which is composed of subjective
      experiences in the multisensory world; however, little is known about the
      subthreshold membrane potential responses of individual hippocampal neurons to
      sensory stimuli. Using in-vivo whole-cell patch-clamp recordings from hippocampal
      CA1 neurons in awake mice, we found that almost all hippocampal neurons exhibited
      a hyperpolarization of 1-2 mV immediately after the onset of a sound. This large
      scale hyperpolarization was unaffected by the duration or pitch of the tone. The
      response was abolished by general anesthesia and a surgical fimbria-fornix
      lesion. 

PMID- 25050475
TI  - Genome-wide characterization and prediction of Arabidopsis thaliana replication
      origins.
AB  - Identification of replication origins is crucial for the faithful duplication of
      genomic DNA. The frequencies of single nucleotides and dinucleotides, GC/AT bias
      and GC/AT profile in the vicinity of Arabidopsis thaliana replication origins
      were analyzed in the present work. The guanine content or cytosine content is
      higher in origin of replication (Ori) than in non-Ori. The SS (S=G or C)
      dinucleotides are favoured in Ori whereas WW (W=A or T) dinucleotides are
      favoured in non-Ori. GC/AT bias and GC/AT profile in Ori are significantly
      different from that in non-Ori. Furthermore, by inputting DNA sequence features
      into support vector machine, we distinguished between the Ori and non-Ori regions
      in A. thaliana. The total prediction accuracy is about 69.5% as evaluated by the
      10-fold cross-validation. This result suggested that apart from DNA sequence,
      deciphering the selection of replication origin must integrate many other factors
      including nucleosome positioning, DNA methylation, histone modification, etc. In
      addition, by comparing predictive performance we found that the predictive
      accuracy of SVM using sequence features on the context of WS language is
      significantly better than that of RY language. Furthermore, the same conclusion
      was also obtained in S. cerevisiae and D. melanogaster. 

PMID- 25050476
TI  - Detection of cardiac ischaemia using bispectral analysis approach.
AB  - This paper highlights a new detection method based on higher spectral analysis
      techniques to distinguish the Electrocardiogram (ECG) of normal healthy subjects
      from that with a cardiac ischaemia (CI) patient. Higher spectral analysis
      techniques provide in-depth information other than available conventional
      spectral analysis techniques usually used with ECG analysis. They provide
      information within frequency parts and information regarding phase associations.
      Bispectral analysis- Bispectrum and Quadratic Phase Coupling techniques are
      utilized to detect as well as to characterize phase combined harmonics in ECG.
      The work is developed, tested and validated using Normal Sinus Rhythm Data from
      the MIT-BIH Database and CI data from the ST Petersburg European ST-T Database.
      The results validate the efficacy of the introduced method by maintaining 100%
      sensitivity and achieving 93.33% positive predictive accuracy. The simplicity and
      robustness of the proposed method makes it feasible to be used within available
      ECG systems.

PMID- 25050480
TI  - Electrochemical enzymatic biosensor with long-term stability using hybrid
      mesoporous membrane.
AB  - An acetylcholinesterase-immobilized sensor unit was successfully prepared by
      encapsulating the enzyme within hybrid mesoporous silica membranes (F127-MST).
      Through a novel combination with tetracyanoquinodimethane, both acetylcholine and
      organophosphorus pesticides were successfully detected with high sensitivity.
      Furthermore, we manufactured the working prototype of an enzyme sensor with this
      sensor unit for detecting dichlorvos, aldicarb and parathion. At present, the
      detection limit in this working prototype either equaled or surpassed that of
      others. Also, we have the advantage of increased stability of the enzyme against
      the outer environment by encapsulation of the enzymes into a silica nanospace.
      Consequently, acetylcholinesterase immobilized in F127-MST is a practical sensor
      with high sensitivity, reusability, and storage stability. 

PMID- 25050479
TI  - Influence of microwave frequency electromagnetic radiation on terpene emission
      and content in aromatic plants.
AB  - Influence of environmental stress factors on both crop and wild plants of
      nutritional value is an important research topic. The past research has focused
      on rising temperatures, drought, soil salinity and toxicity, but the potential
      effects of increased environmental contamination by human-generated
      electromagnetic radiation on plants have little been studied. Here we studied the
      influence of microwave irradiation at bands corresponding to wireless router
      (WLAN) and mobile devices (GSM) on leaf anatomy, essential oil content and
      volatile emissions in Petroselinum crispum, Apium graveolens and Anethum
      graveolens. Microwave irradiation resulted in thinner cell walls, smaller
      chloroplasts and mitochondria, and enhanced emissions of volatile compounds, in
      particular, monoterpenes and green leaf volatiles (GLV). These effects were
      stronger for WLAN-frequency microwaves. Essential oil content was enhanced by GSM
      frequency microwaves, but the effect of WLAN-frequency microwaves was inhibitory.
      There was a direct relationship between microwave-induced structural and chemical
      modifications of the three plant species studied. These data collectively
      demonstrate that human-generated microwave pollution can potentially constitute a
      stress to the plants. 

PMID- 25050481
TI  - Diffusional transport to and through thin-layer nanoparticle film modified
      electrodes: capped CdSe nanoparticle modified electrodes.
AB  - We present a simple and general theoretical model which accounts fully for the
      influence of an electrode modifying non-electroactive layer on the voltammetric
      response of a diffusional redox probe. The layer is solely considered to alter
      the solubilities and diffusion coefficients of the electroactive species within
      the thin layer on the electrode surface. On this basis it is demonstrated how,
      first, the apparent electrochemical rate constant can deviate significantly from
      that measured at an unmodified electrode. Second, depending on the conditions
      within the layer the modification of the electrode may lead to either apparent
      'negative' or 'positive' electrocatalytic effects without the true standard
      electrochemical rate constant for the electron transfer at the electrode surface
      being altered. Having presented the theoretical model three experimental cases
      are investigated, specifically, the reductions of ruthenium(III) hexaamine,
      oxygen and boric acid on a gold macro electrode with and without a multi-layer
      organic capped nanoparticle film. In the latter case of the reduction of boric
      acid the voltammetric reduction is found to be enhanced by the presence of the
      organic layer. This result is interpreted as being due to an increase in the
      solubility of the analyte within the non-electroactive layer and not due to an
      alteration of the standard electrochemical rate constant.

PMID- 25050482
TI  - Design, synthesis and biological evaluation of bicyclic iminosugar hybrids:
      conformational constraint as an effective tool for tailoring the selectivity of
      alpha-glucosidase inhibitors.
AB  - Principle guided design of glycan processing enzyme inhibitors involves embedding
      aromatic groups onto charge and shape mimics. Intramolecular azide-alkyne
      cycloaddition was used as a simple and versatile strategy for the synthesis of
      novel condensed bicyclic triazoles from carbohydrate derived Perlin aldehydes.
      These newly synthesised molecules were evaluated for glycosidase inhibition
      against 11 commercially available enzymes and were found to possess significant
      affinity (micromolar range) as well as high degree of selectivity for alpha
      glucosidases. Conformational restriction was identified as an important tool to
      customize the selectivity of enzyme inhibition by five-membered iminosugars. 

PMID- 25050483
TI  - Targeting complement anaphylatoxin C5a receptor in hyperoxic lung injury in mice.
AB  - Receptor binding of complement anaphylatoxin C5a results in proinflammatory
      activation of numerous diseases, but the role of receptor-mediated action during
      hyperoxic lung injury has, to the best of our knowledge, not yet been
      investigated. The contribution of the C5a receptor (C5aR) to hyperoxic lung
      injury in mice was investigated in this study. The effect of C5aR on hyperoxic
      lung injury in Balb/c mice was examined employing a C5aR antagonist (C5aRA). The
      mice were ventilated with 100% oxygen for 36 h with or without the administration
      of C5aRA. C5aR expression levels in non-treated or 100% oxygen-treated mice were
      assessed by reverse transcription polymerase chain reaction (RT-PCR) and flow
      cytometry. The body weight and the relative lung weight of the mice, and the
      morphological changes in the lung were then determined. The total cell counts and
      the number of macrophages, neutrophils and lymphocytes in bronchoalveolar lavage
      fluid (BALF) were determined using cytocentrifuge slides and a hemocytometer. The
      levels of interleukin-6 (IL-6), monocyte chemotactic protein (MCP-1) and tumor
      necrosis factor-alpha (TNF-alpha) in BALF and the myeloperoxidase (MPO) activity
      in the lung tissue were measured by enzyme-linked immunosorbent assay. The
      relative levels of CD68 and F4/80 messenger ribonucleic acid (mRNA) expression in
      the lung tissue were detected by RT-PCR. The TNF-alpha, IL-6 and MCP-1 protein
      expression levels in the lung tissue were assessed by western blot analysis. The
      results revealed hyperoxia-induced morphological changes, lung injury and
      increased expression levels of C5aR in lung tissue. The hyperoxia-induced
      increases in the total cell count and the number of macrophages, neutrophils and
      lymphocytes in the BALF were all significantly reduced in the mice receiving
      C5aRA. Treatment with C5aRA also attenuated the morphological changes and reduced
      MPO activity, and CD68 and F4/80 mRNA expression levels in the lung tissue, as
      well as the levels of IL-6, MCP-1 and TNF-alpha in BALF and lung tissue. In
      conclusion, C5a-C5aR action accelerated hyperoxia-induced lung injury, but this
      hyperoxic lung injury was attenuated by treatment with C5aRA.

PMID- 25050485
TI  - Berberine induces apoptosis and DNA damage in MG-63 human osteosarcoma cells.
AB  - Berberine, an isoquinoline alkaloid extracted from the dry root of Coptidis
      Rhizoma, has been found to exhibit marked anticancer effects on a panel of
      established cancer cells. Among the human osteosarcoma lines treated, MG-63 cells
      were found to be the most sensitive. The present study investigated the potential
      genotoxic effect of berberine on MG-63 human osteosarcoma cells. The effect of
      berberine on cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay and cell apoptosis was analyzed by flow
      cytometry and a DNA ladder assay. gammaH2AX focus formation was used to detect
      DNA damage in MG-63 cells. Berberine induced a significant increase in apoptosis
      in MG-63 cells in a concentration- and time-dependent manner, as determined by
      DNA fragmentation analysis and flow cytometry. Furthermore, berberine induced
      significant concentration- and time-dependent increases in DNA damage compared
      with that in the negative control. In conclusion, these observations indicated
      that berberine induced apoptosis and DNA damage in MG-63 cells.

PMID- 25050487
TI  - Vaccination: an evolutionary engine for pathogens? Conference report.

PMID- 25050486
TI  - Study of Polymorphisms in CX3CR1, PLEKHA1 and VEGF genes as risk factors for age
      related macular degeneration in Indian patients.
AB  - BACKGROUND AND AIMS: Age-related macular degeneration (AMD) is an important cause
      of visual impairment in elderly persons. AMD is a multifactorial disease in which
      both environmental and genetic factors have been implicated. Various single
      nucleotide polymorphisms (SNPs) have been found to be associated with AMD. This
      study aimed to investigate the association of polymorphisms in CX3CR1, PLEKHA1
      and VEGF genes with AMD in Indian patients. METHODS: Genotyping for the CX3CR1
      T280M (C>T) and V249I (G>A), PLEKHA1 A320T (G>A) &VEGF +674 (C>T) and +936 (C>T)
      was performed in 121 AMD patients and 100 controls by polymerase chain reaction,
      restriction fragment length polymorphism (PCR-RFLP) and sequencing method.
      RESULTS: The genotype analysis of VEGF gene polymorphisms (+674 and +936) showed
      a significant association with AMD. Odds ratios for VEGF (+674) and VEGF (+936)
      were 2.37 and 2.50 with a p value 0.0029 and 0.0358 for the autosomal dominant
      model. CX3CR1 (T280M and V249I) and PLEKHA1 (A320T) polymorphisms were not found
      to be associated with AMD. Odds ratios for mutant alleles of T280M and V249I
      polymorphisms in CX3CR1 gene were 0.95 and 0.83, respectively, compared to the
      wild-type alleles. Odds ratio for the polymorphism in the PLEKHA1 gene was 0.63.
      CONCLUSIONS: The present study suggests that both polymorphisms in VEGF gene are
      risk factors for AMD in the Indian population. Detection of individuals at risk
      could lead to strategies for prevention, early diagnosis and management of AMD.

PMID- 25050488
TI  - Hepeviridae: an expanding family of vertebrate viruses.
AB  - The hepatitis E virus (HEV) was first identified in 1990, although hepatitis E
      like diseases in humans have been recorded for a long time dating back to the
      18th century. The HEV genotypes 1-4 have been subsequently detected in human
      hepatitis E cases with different geographical distribution and different modes of
      transmission. Genotypes 3 and 4 have been identified in parallel in pigs, wild
      boars and other animal species and their zoonotic potential has been confirmed.
      Until 2010, these genotypes along with avian HEV strains infecting chicken were
      the only known representatives of the family Hepeviridae. Thereafter, additional
      HEV-related viruses have been detected in wild boars, distinct HEV-like viruses
      were identified in rats, rabbit, ferret, mink, fox, bats and moose, and a
      distantly related agent was described from closely related salmonid fish. This
      review summarizes the characteristics of the so far known HEV-like viruses, their
      phylogenetic relationship, host association and proposed involvement in diseases.
      Based on the reviewed knowledge, a suggestion for a new taxonomic grouping scheme
      of the viruses within the family Hepeviridae is presented. 

PMID- 25050489
TI  - Mono- and bimetallic Ir(III) based catalysts for the homogeneous photocatalytic
      reduction of CO2 under visible light irradiation. New insights into catalyst
      deactivation.
AB  - Mononuclear iridium(III) complexes [Ir(mppy)(tpy)X] (mppy = 4-methyl-2
      phenylpyridine, X = Cl, I) and binuclear analogues with various bis(2
      phenylpyridin-4-yl) bridging ligands were synthesized and characterized by their
      spectroscopic and electrochemical properties. Kinetic measurements concerning the
      photocatalytic two electron reduction of CO2 to CO were investigated in order to
      determine the influence of intermolecular interactions between two active
      centers. A detailed comparison between the monometallic and the bimetallic
      complexes indicates an enhanced lifetime (TON) of the covalently linked
      complexes, causing an increased overall conversion of CO2. Additionally the
      deactivation pathways of the catalysts are examined.

PMID- 25050490
TI  - Cold atmospheric plasma treatment selectively targets head and neck squamous cell
      carcinoma cells.
AB  - The treatment of locoregional recurrence (LRR) of head and neck squamous cell
      carcinoma (HNSCC) often requires a combination of surgery, radiation therapy
      and/or chemotherapy. Survival outcomes are poor and the treatment outcomes are
      morbid. Cold atmospheric plasma (CAP) is an ionized gas produced at room
      temperature under laboratory conditions. We have previously demonstrated that
      treatment with a CAP jet device selectively targets cancer cells using in vitro
      melanoma and in vivo bladder cancer models. In the present study, we wished to
      examine CAP selectivity in HNSCC in vitro models, and to explore its potential
      for use as a minimally invasive surgical approach that allows for specific cancer
      cell or tumor tissue ablation without affecting the surrounding healthy cells and
      tissues. Four HNSCC cell lines (JHU-022, JHU-028, JHU-029, SCC25) and 2 normal
      oral cavity epithelial cell lines (OKF6 and NOKsi) were subjected to cold plasma
      treatment for durations of 10, 30 and 45 sec, and a helium flow of 20 l/min-1 for
      10 sec was used as a positive treatment control. We showed that cold plasma
      selectively diminished HNSCC cell viability in a dose-response manner, as
      evidenced by MTT assays; the viability of the OKF6 cells was not affected by the
      cold plasma. The results of colony formation assays also revealed a cell-specific
      response to cold plasma application. Western blot analysis did not provide
      evidence that the cleavage of PARP occurred following cold plasma treatment. In
      conclusion, our results suggest that cold plasma application selectively impairs
      HNSCC cell lines through non-apoptotic mechanisms, while having a minimal effect
      on normal oral cavity epithelial cell lines.

PMID- 25050491
TI  - Cyclosporine protects the heart during aortic valve surgery.
AB  - BACKGROUND: Part of the myocardial damage occurring during cardiac surgery is a
      consequence of reperfusion injury. Cyclosporine, a potent inhibitor of the
      opening of the mitochondrial permeability transition pore, attenuates reperfusion
      injury in patients with acute ST-segment elevation myocardial infarction. This
      study investigated whether the administration of cyclosporine just before the
      aortic cross-unclamping would reduce myocardial injury in patients undergoing
      aortic valve surgery. METHODS: This study was a monocentric, prospective,
      randomized, single-blinded, controlled trial. Sixty-one patients, scheduled for
      elective aortic valve surgery, were randomly assigned (computer-generated
      randomization sequence) to receive either an intravenous bolus of cyclosporine
      (2.5 mg/kg, cyclosporine group, n = 30) or normal saline (control group, n = 31)
      10 min before aortic cross-unclamping. The primary endpoint was the 72-h area
      under the curve for cardiac troponin I. RESULTS: Both groups were similar with
      respect to baseline characteristics and aortic cross-clamping duration. A
      significant 35% reduction of area under the curve for cardiac troponin I was
      observed in the cyclosporine group compared with the control group (242 +/- 225
      vs. 155 +/- 71 arbitrary units, mean +/- SD; mean difference, -86.2 +/- 42.5; 95%
      CI, -172.3 to -0.1; P = 0.03). Cyclosporine beneficial effect remained
      significant after adjustment for aortic cross-clamping duration in each group
      (mean difference, -88 +/- 34, 95% CI, -157 to -19; P = 0.01). None of the treated
      patients had significant side effects (odds ratio, 0.64; 95% CI, 0.16 to 2.55; P
      = 0.52). CONCLUSIONS: Cyclosporine administration at the time of reperfusion
      protects against reperfusion injury in patients undergoing aortic valve surgery.
      The clinical benefit of this protection requires confirmation in a larger
      clinical trial.

PMID- 25050492
TI  - Wine before swine: circe's anticholinergic potion.

PMID- 25050493
TI  - Holy Moly: Hermes' anticholinesterase antidote.

PMID- 25050494
TI  - Perioperative positive pressure ventilation: an integrated approach to improve
      pulmonary care.

PMID- 25050495
TI  - Paul meyer wood and his collectibles: packing and moving.

PMID- 25050496
TI  - Double trouble ... less often.

PMID- 25050497
TI  - Difficult face-mask ventilation and difficult laryngoscopy.

PMID- 25050498
TI  - In reply.

PMID- 25050499
TI  - Gabapentinoids and postsurgical pain: safe and effective?

PMID- 25050500
TI  - Emerging perspectives in perioperative use of gabapentinoids.

PMID- 25050501
TI  - In reply.

PMID- 25050502
TI  - Academic anesthesia: innovate to avoid extinction.

PMID- 25050503
TI  - In reply.

PMID- 25050504
TI  - Simulator training for transesophageal echocardiography.

PMID- 25050505
TI  - In reply.

PMID- 25050506
TI  - Corporate interests necessitate conflict of interest declarations by all authors.

PMID- 25050507
TI  - In reply.

PMID- 25050508
TI  - In reply.

PMID- 25050509
TI  - Is norepinephrine infusion during intraoperative period justified?

PMID- 25050510
TI  - In reply.

PMID- 25050515
TI  - A brief history of femoral nerve blocks.

PMID- 25050517
TI  - Ingenines A and B, Two New Alkaloids from the Indonesian Sponge
      Acanthostrongylophora ingens.
AB  - As a continuation of the work on EtOAc fraction of the Indonesian sponge
      Acanthostrongylophora ingens, 2 new alkaloids: one pyrimidine-beta-carboline
      alkaloid named ingenine A (2) and one pyrimidine-gamma-carboline alkaloid named
      ingenine B (3), along with annomontine (1) were isolated. Their structures were
      unambiguously established on the basis of NMR spectroscopy ((1) H, (13)C, (1) H
      (1) H COSY, HMQC, and HMBC) and mass spectral data. This is the first report of
      isolation pyrimidine-gamma-carboline alkaloid from natural source. Compounds 1
      and 3 showed pronounced cytotoxicity against the murine lymphoma L5178Y cancer
      cell line with ED50 7.8 and 9.1 MUg/mL respectively, while compound 2 showed weak
      activity. 

PMID- 25050518
TI  - Impact of Supplementation with Curcuminoids on Systemic Inflammation in Patients
      with Knee Osteoarthritis: Findings from a Randomized Double-Blind Placebo
      Controlled Trial.
AB  - OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease associated with
      inflammation. The present study aimed to determine changes in serum levels of
      inflammatory biomarkers in OA patients whose clinical symptoms were improved as a
      result of supplementation with curcuminoids. METHODS: This study was a randomized
      double-blind placebo-control parallel-group clinical trial in which 40 subjects
      with mild-to-moderate degree knee OA were randomly allocated to receive either
      pure curcuminoids (1,500 mg/day in 3 divided doses; n=19) or matched placebo
      (n=21) for 6 weeks. In order to enhance the bioavailability of curcuminoids,
      piperine (15 mg/day) was added to the treatment regimen. Serum levels of
      interleukins 4 (IL-4) and 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha),
      transforming growth factor-beta (TGF-beta) and high-sensitivity C-reactive
      protein (hs-CRP), together with erythrocyte sedimentation rate (ESR) were
      determined at baseline as well as at the end of trial. RESULTS: Serum
      concentrations of IL-4 (p=0.001), IL-6 (p=0.006) and hs-CRP (p=0.004) were
      significantly reduced in the curcuminoid group whilst serum levels of TNF-alpha
      and TGF-beta and mean ESR remained unaltered by the end of trial (p>0.05). In the
      placebo group, serum concentrations of IL-4 (p=0.001), IL-6 (p=0.003), TNF-alpha
      (p=0.003) and TGF-beta (p=0.005) were significantly reduced but mean hs-CRP and
      ESR values remained statistically unchanged (p>0.05). Comparison of the magnitude
      of changes in the evaluated inflammatory biomarkers did not indicate any
      significant difference between the study groups (p>0.05). CONCLUSION: Significant
      improvement in clinical symptoms of OA in curcuminoid-treated subjects cannot be
      attributed to the systemic anti-inflammatory effects of these phytochemicals.

PMID- 25050519
TI  - Nitrosative Stress and Apoptosis by Intravenous Ferumoxytol, Iron Isomaltoside
      1000, Iron Dextran, Iron Sucrose, and Ferric Carboxymaltose in a Nonclinical
      Model.
AB  - Iron is involved in the formation as well as in the scavenging of reactive oxygen
      and nitrogen species. Thus, iron can induce as well as inhibit both oxidative and
      nitrosative stress. It also has a key role in reactive oxygen and nitrogen
      species-mediated apoptosis. We assessed the differences in tyrosine nitration and
      caspase 3 expression in the liver, heart, and kidneys of rats treated weekly with
      intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose and
      ferric carboxymaltose (40 mg iron/kg body weight) for 5 weeks. Nitrotyrosine was
      quantified in tissue homogenates by Western blotting and the distribution of
      nitrotyrosine and caspase 3 was assessed in tissue sections by
      immunohistochemistry. Ferric carboxymaltose and iron sucrose administration did
      not result in detectable levels of nitrotyrosine or significant levels of caspase
      3 vs. control in any of the tissue studied. Nitrotyrosine and caspase 3 levels
      were significantly (p<0.01) increased in all assessed organs of animals treated
      with iron dextran and iron isomaltoside 1000, as well as in the liver and kidneys
      of ferumoxytol-treated animals compared to isotonic saline solution (control).
      Nitrotyrosine and caspase 3 levels were shown to correlate positively with the
      amount of Prussian blue-detectable iron(III) deposits in iron dextran- and iron
      isomaltoside 1000-treated rats but not in ferumoxytol-treated rats, suggesting
      that iron dextran, iron isomaltoside 1000 and ferumoxytol induce nitrosative (and
      oxidative) stress as well as apoptosis via different mechanism(s). 

PMID- 25050520
TI  - Comparative Study of Three Traditional Mongolian Medicines on Streptozotocin
      induced Diabetic Nephropathy in Rats.
AB  - 3 kinds of prescription of Traditional Mongolian (Chinese) Medicine (TMM) have
      been used in treating diabetic nephropathy (DN). We aimed to investigate: first,
      which prescription was more effective; second, whether it was more effective when
      combined with the 3 prescriptions. The DN model was prepared by a single dose of
      Streptozotocin (STZ, 65 mg/kg, i.p.) in rats and treated 3 times every day with P
      1 (Sugmul-10), P-2 (Narenmandul-11), P-3 (Xieriga-4) respectively, and combined
      group was treated with P-1 in the morning, P-2 and P-3 in the evening. The
      results showed combining with 3 prescriptions in one day was much more effective
      than each single prescription. The mechanism of renal protection maybe related to
      MMP-2 and TGF-beta1, the conclusion could be useful and beneficial for clinical
      medicine.

PMID- 25050521
TI  - Effect of etanercept, infliximab and methotrexate in the treatment of arthritis.
AB  - BACKGROUND: Rheumatoid arthritis a chronic inflammatory autoimmune disease with
      inflammation of the joint, leading to damage of bone and surrounding cartilage.
      OBJECTIVES: Our study was designed to find the efficacy of etanercept, infliximab
      and methotrexate in effective therapeutic management against arthritis patients.
      METHODS: A total of 315 patients, including both the sexes in the age group of 45
      70 years with active rheumatoid arthritis attending Hospital of Academy of
      Military Medical Sciences, Beijing, China during the period of December 2012 to
      November 2013 were included in the study. 100 patients with joint pains, but not
      with rheumatoid arthritis were taken as a control group. All the patients were
      treated with infliximab, methotrexate and etanercept. RESULTS: In our study,
      patients responded, 75% to infliximab and etanercept combinations than to
      methotrexate. The combination therapy also showed a radiological decrease in the
      joint damage. There is significant when combinations of these drugs were used for
      the therapy (P<0.001). CONCLUSION: In our study, use of infliximab and etanercept
      combinations lowered the joint damage and helped in the improvement of the
      patient's life.

PMID- 25050522
TI  - Lipid peroxidation and altered anti-oxidant status in breast adenocarcinoma
      patients.
AB  - INTRODUCTION: Breast cancer is the one of most common cancer in worldwide which
      accounts for high mortality rate. Accumulating evidences emphasizes increased
      oxidative stress plays a major role in the pathogenesis of solid tumors. Hence
      the current study was carried out to measure the extent of lipid peroxidation and
      antioxidants as biomarkers of human breast ade-no-carcinoma patients. METHODS:
      The collected tissues and blood samples from cancer patients and control groups
      were subjected to determine the extent of lipid peroxidation by measuring the
      levels of malondialdehyde (MDA), lipid hydroperoxides (LOOH) and conjugated
      dienes (CDs) as well as the status of the antioxidants such as superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) by UV visible
      spectrophotometer. RESULTS: Lipid peroxidation in breast cancer tissues was
      significantly enhanced in conjunction with the significant increase in both
      enzymic and non-enzymic antioxidants when compared to the healthy controls.
      CONCLUSION: Increased lipid peroxidation is more pronounced in breast cancer
      patients and as a adaptive mechanism antioxidants system was upregulated.
      Therefore, measurement of oxidative stress will be an affective prognosis factor
      and that may aid to design new therapeutic drugs for cancer treatment.

PMID- 25050523
TI  - Bacterial metabolism of methylated amines and identification of novel
      methylotrophs in Movile Cave.
AB  - Movile Cave, Romania, is an unusual underground ecosystem that has been sealed
      off from the outside world for several million years and is sustained by non
      phototrophic carbon fixation. Methane and sulfur-oxidising bacteria are the main
      primary producers, supporting a complex food web that includes bacteria, fungi
      and cave-adapted invertebrates. A range of methylotrophic bacteria in Movile Cave
      grow on one-carbon compounds including methylated amines, which are produced via
      decomposition of organic-rich microbial mats. The role of methylated amines as a
      carbon and nitrogen source for bacteria in Movile Cave was investigated using a
      combination of cultivation studies and DNA stable isotope probing (DNA-SIP) using
      (13)C-monomethylamine (MMA). Two newly developed primer sets targeting the gene
      for gamma-glutamylmethylamide synthetase (gmaS), the first enzyme of the recently
      discovered indirect MMA-oxidation pathway, were applied in functional gene
      probing. SIP experiments revealed that the obligate methylotroph Methylotenera
      mobilis is one of the dominant MMA utilisers in the cave. DNA-SIP experiments
      also showed that a new facultative methylotroph isolated in this study,
      Catellibacterium sp. LW-1 is probably one of the most active MMA utilisers in
      Movile Cave. Methylated amines were also used as a nitrogen source by a wide
      range of non-methylotrophic bacteria in Movile Cave. PCR-based screening of
      bacterial isolates suggested that the indirect MMA-oxidation pathway involving
      GMA and N-methylglutamate is widespread among both methylotrophic and non
      methylotrophic MMA utilisers from the cave. 

PMID- 25050525
TI  - Centimeter-long electron transport in marine sediments via conductive minerals.
AB  - Centimeter-long electron conduction through marine sediments, in which electrons
      derived from sulfide in anoxic sediments are transported to oxygen in surficial
      sediments, may have an important influence on sediment geochemistry. Filamentous
      bacteria have been proposed to mediate the electron transport, but the filament
      conductivity could not be verified and other mechanisms are possible.
      Surprisingly, previous investigations have never actually measured the sediment
      conductivity or its basic physical properties. Here we report direct measurements
      that demonstrate centimeter-long electron flow through marine sediments, with
      conductivities sufficient to account for previously estimated electron fluxes.
      Conductivity was lost for oxidized sediments, which contrasts with the previously
      described increase in the conductivity of microbial biofilms upon oxidation.
      Adding pyrite to the sediments significantly enhanced the conductivity. These
      results suggest that the role of conductive minerals, which are more commonly
      found in sediments than centimeter-long microbial filaments, need to be
      considered when modeling marine sediment biogeochemistry. 

PMID- 25050524
TI  - Elevated temperature alters proteomic responses of individual organisms within a
      biofilm community.
AB  - Microbial communities that underpin global biogeochemical cycles will likely be
      influenced by elevated temperature associated with environmental change. Here, we
      test an approach to measure how elevated temperature impacts the physiology of
      individual microbial groups in a community context, using a model microbial-based
      ecosystem. The study is the first application of tandem mass tag (TMT)-based
      proteomics to a microbial community. We accurately, precisely and reproducibly
      quantified thousands of proteins in biofilms growing at 40, 43 and 46  degrees C.
      Elevated temperature led to upregulation of proteins involved in amino-acid
      metabolism at the level of individual organisms and the entire community.
      Proteins from related organisms differed in their relative abundance and
      functional responses to temperature. Elevated temperature repressed carbon
      fixation proteins from two Leptospirillum genotypes, whereas carbon fixation
      proteins were significantly upregulated at higher temperature by a third member
      of this genus. Leptospirillum group III bacteria may have been subject to viral
      stress at elevated temperature, which could lead to greater carbon turnover in
      the microbial food web through the release of viral lysate. Overall, these
      findings highlight the utility of proteomics-enabled community-based physiology
      studies, and provide a methodological framework for possible extension to
      additional mixed culture and environmental sample analyses. 

PMID- 25050526
TI  - Extraction of a coronary sinus lead: always so easy?

PMID- 25050527
TI  - Pseudoaneurysm of the mitral-aortic intervalvular fibrosa.
AB  - A pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare but
      potentially fatal complication seen primarily in the context of infective
      endocarditis. In this study, we discuss a case of infective endocarditis that was
      complicated by the rupture of a pseudoaneurysm of the mitral-aortic intervalvular
      fibrosa. We review the salient echocardiographic findings of this clinical
      condition. 

PMID- 25050528
TI  - Left atrium assessment: the evolving role of MRI.
AB  - The left atrium plays an integral role in cardiac performance. Data regarding the
      left atrial size, volume, function, and structure are clinically important in the
      management of patients with different diagnoses. Moreover, left atrial size and
      function were recognized as robust predictors of poor outcome across a broad
      range of cardiac diseases. These data are usually obtained using
      echocardiography. MRI can be used as an alternative tool or in clinical or
      experimental situations when more exact and detailed assessment is required. In
      the left atrial functional analysis, MRI is considered to be a gold standard
      technique that overcomes many of the limitations associated with
      echocardiographic assessment. In comparison with the other techniques, late
      gadolinium enhancement provides a unique opportunity to assess left atrial
      myocardial tissue in vivo. Complex cardiac magnetic resonance data may help to
      make a diagnosis, determine a prognosis and provide an impact on therapeutic
      actions.This review summarizes the potential role of cardiac magnetic resonance
      in left atrium assessment, with special emphasis on recent data and the potential
      future research directions. 

PMID- 25050529
TI  - Current management of double-outlet left ventricle: towards biventricular repair
      in infancy.
AB  - BACKGROUND: Double-outlet left ventricle (DOLV) is an extremely rare type of
      ventriculoarterial connection, mostly reported anecdotally with wide variations
      in morphology, surgical strategy and clinical outcome. The aim of the present
      study was to define current morbidity and mortality of biventricular repair and
      discuss surgical management in infancy. METHODS: Inclusion criteria were English
      literature publication; balanced ventricular development and completion of
      biventricular repair. Institutional experience was also reported. Study end
      points were survival and freedom from cardiovascular events. Univariate analysis
      to identify risk factors for complications was performed. RESULTS: During a 45
      year interval, 37 cases of DOLV were identified. Median age at repair was 48
      months (range 0.3-336); seven patients were infants. Extracardiac repair was
      performed in 21 (57%) patients, right ventricular outflow patch in seven,
      pulmonary translocation in six, and intraventricular repair in three. There were
      three (8%) hospital deaths, due to right heart failure, and seven (21%) patients
      experienced 10 perioperative complications. Univariate analysis showed year of
      operation (P = 0.02) and outflow patch technique (P = 0.003) as risk factors for
      hospital morbidity and mortality. During a median follow-up of 26 months (range 1
      192), there was one death and seven reoperations. Ten-year survival and freedom
      from adverse cardiovascular events were 87 +/- 6 and 70 +/- 10%, respectively.
      CONCLUSION: Although seldom reported in the past, repair of DOLV in infancy does
      not increase surgical risk. Early and late morbidity are mostly due to right
      heart complications and more common after right ventricular outflow patch repair.
      Paucity of follow-up information may underestimate actual late adverse event
      rate.

PMID- 25050530
TI  - Impact of metabolic syndrome traits on cardiovascular function: should the Adult
      Treatment Panel III definition be further stratified?
AB  - AIMS: The aims of the study were to evaluate whether a further classification of
      metabolic syndrome according to the number of traits (based on the Adult
      Treatment Panel III definition) could better explain the impact on cardiovascular
      remodeling and function, and to assess the role of single metabolic syndrome
      components in this regard. METHODS: We studied by echocardiography and carotid
      ultrasound 435 asymptomatic patients with metabolic syndrome. Patients with
      coronary artery disease or more than mild valvular heart disease were excluded.
      Carotid stiffness index (beta) was measured using a high-resolution echo-tracking
      system. Patients with metabolic syndrome were divided into two groups: metabolic
      syndrome with three traits (Gr.1) and metabolic syndrome with four or five traits
      (Gr. 2). RESULTS: Patients in Gr. 2 had higher left ventricular mass index (P <
      0.001), left ventricular end-diastolic volume index (P = 0.029), left atrial
      volume index (P = 0.002), E/e' ratio (P = 0.002), intima-media thickness (P =
      0.031), and prevalence of plaques (P = 0.01) than patients in Gr. 1. Left
      ventricular ejection fraction was similar in both groups. The mean carotid beta
      index tended to be higher in Gr. 2. Considering metabolic syndrome traits
      separately, in an age-corrected multivariate analysis, abdominal obesity was
      found to have the strongest association with cardiac structure and carotid artery
      atherosclerosis and stiffness. CONCLUSION: An increasing number of metabolic
      syndrome traits had a significantly worse impact on cardiac remodeling and
      function and carotid artery atherosclerosis. Abdominal obesity showed the
      strongest association with cardiac structure, carotid artery stiffness, and
      intima-media thickness. Prospective studies are needed to evaluate whether a new
      classification of metabolic syndrome using the number of traits could add
      prognostic information.

PMID- 25050531
TI  - How to recognize endomyocardial fibrosis?
AB  - Endomyocardial fibrosis is a disease of unknown cause, characterized by the
      development of restrictive cardiomyopathy. Although it is endemic in Africa, some
      cases have been described in Asia, South America and Europe, where a substantial
      unfamiliarity with this disease still exists. Moreover, differential diagnosis of
      endomyocardial fibrosis with other cardiomyopathies can be difficult, especially
      in asymptomatic patients and in initial stage of the disease. After initial
      echocardiographic analysis, the gold standard imaging technique is the cardiac
      magnetic resonance. Adjunctive diagnostic tools as endomyocardial biopsy can be
      considered in ambiguous cases and can help in patient management. 

PMID- 25050532
TI  - Acute myocardial infarction as first manifestation of left atrial myxoma in a
      young woman: role of echocardiography.
AB  - We report the case of a young woman with an acute myocardial infarction secondary
      to coronary embolization from a left atrial myxoma, as unusual presentation of a
      cardiac tumor.We also describe the role of transthoracic echocardiograpy in the
      multidisciplinary approach to diagnosis and treatment of this life-threatening
      condition. 

PMID- 25050533
TI  - Low and high doses of UV-B differentially modulate chlorpyrifos-induced
      alterations in nitrogen metabolism of cyanobacteria.
AB  - The present study assessed the comparative responses on the specific growth rate,
      nitrogen metabolism and enzymes associated with nitrogen metabolism in two
      nitrogen fixing cyanobacteria-Nostoc muscorum and Phormidium foveolarum exposed
      to two UV-B doses (low; UV-BL: 0.5472kJm(-2) and high; UV-BH: 5.472kJm(-2)) and
      two doses of the insecticide chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2
      pyridyl phosphorothioate; low i.e. CPL, 1ugml(-1) and high i.e. CPH, 2ugml(-1))
      singly and in combination. The specific growth rate, NO3(-) and NO2(-) uptake,
      nitrate assimilating enzymes - nitrate reductase and nitrite reductase and
      ammonium assimilating enzymes - glutamine synthetase and glutamate synthase were
      severely affected when treated either with CPH or/and UV-BH while glutamate
      dehydrogenase exhibited a stimulatory response. CPL also reduced all the measured
      parameters (except GDH activity) after 24h, however, a stimulatory effect was
      observed after 72h due to an increase in nitrogen metabolism (and other
      antioxidant) enzymes during this period. UV-BL did not cause significant
      alteration in the studied parameters while in combination with CP doses, it
      either alleviated the inhibitory effects or further enhanced the CPL induced
      activities of these enzymes (except GDH). Overall results indicate the resistant
      nature of P. foveolarum against the inhibitory doses of UV-B and chlorpyrifos in
      comparison to N. muscorum.

PMID- 25050534
TI  - The trans-generation effect during pulsed cadmium exposure: tolerance and
      induction of hsp70.
AB  - Although the importance of pulse exposure has gained ground in recent years, it
      still needs to be better evaluated and understood. Two successive generations of
      Daphnia magna were exposed to four concentrations (40, 60, 80 and100ugCdl(-1)) of
      6h cadmium (Cd) pulses. The increase of pulsed concentration of parent generation
      (F0) led to the decrease of EC50 and an increase of 21-day cumulative mortality
      of the first generation of offspring (F1). The mortality of F1 has a
      significantly higher level than F0 when they experienced the same pulse. Hsp70
      can be induced by Cd pulse and gradually recover to the normal level after
      exposure. But the sensitivity of hsp70 of F1 was lower than F0 and the response
      seemingly was not under the control of heredity. Compared to growth, reproduction
      was more sensitive. The complete risk assessment of pulse exposure should take
      the response of offspring into account, especially in an ecological or field
      context.

PMID- 25050535
TI  - Assessment of mutagenic potential of pyrolysis biochars by Ames
      Salmonella/mammalian-microsomal mutagenicity test.
AB  - Biochar is of raising interest in sustainable biomass utilization concepts.
      Particularly biochar derived from pyrolysis attaches important agricultural
      capacities mandatory for an improved carbon sequestration, soil fertility and
      amelioration, respectively. In fact, large scale field trials and commercial
      business with biochar materials have already been started but still only few are
      known about the mutagenic potential of biochars produced. In this study hemp
      bedding and wood pellet biomass were used for biochar production by pyrolysis.
      The total concentrations of polycyclic aromatic hydrocarbons (PAHs) were 34.9ugg(
      1) of dry mass and 33.7ugg(-1) of dry mass for hemp biochar and wood biochar,
      respectively. The concentration of PAHs in tar produced during wood carbonization
      was 17.4ugg(-1). The concentrations of phenolic compounds were 55ugg(-1) and
      8.3ugg(-1) for hemp and wood biochar, respectively. Salmonella/microsomal
      mutagenicity tests (i.e. Ames test) revealed a maximum mutagenicity for hemp
      biochar extracts with strains TA97, TA98 and TA100 in the presence and absence of
      liver microsomal fractions, respectively. Wood biochar and tar extract exhibited
      maximum mutagenicity with strains TA98 and T100 both in the presence and absence
      of liver microsomal fraction. The reversion of the applied tester strains
      increased in the presence and absence of liver microsomal fractions with an
      increasing dose of hemp biochar extract up to 2ul per plate and decreased at a
      concentration of 2.5ul per plate. For wood biochar and tar extracts, reversion of
      tester strains increased both in the presence and absence of S9 at extract
      concentrations of 4ul per plate and declined at a dose of 8ul per plate. By this
      study a significant higher mutagenic potential for hemp biochar compared to wood
      biochar and tar could be observed suggesting careful application in soil
      melioration.

PMID- 25050536
TI  - The effects of estrone and 17beta-estradiol on microbial activity and bacterial
      diversity in an agricultural soil: sulfamethoxazole as a co-pollutant.
AB  - Estrogens and veterinary antibiotics (VAs) that are contained in animal
      excrements are spread into agricultural soil when using animal wastes on
      farmland. The impacts of VAs on soil health have already been well documented.
      However, there is limited knowledge regarding the influence of estrogens,
      particularly the combined effects of estrogens and VAs, on the soil microbial
      community. In this study, a short-term analysis (11 days) of the effect of the
      estrogens estrone and 17beta-estradiol on soil microbial activity and on
      bacterial community structure was performed using a dehydrogenase activity (DHA)
      test and a PCR-denaturing gradient gel electrophoresis (DGGE) assay,
      respectively. Meanwhile, the potential influence of the VA sulfamethoxazole (SMX)
      as a co-pollutant on the effects of estrogens was examined. It was found that (1)
      estrone and 17beta-estradiol biodegraded within hours in non-sterilized soil,
      even in the presence of up to 100mg/kg SMX. (2) Estrone or 17beta-estradiol alone
      markedly promoted soil DHA and stimulated the growth of partial bacteria strains,
      which were demonstrated as new or more intensive bands in DGGE profiles relative
      to the control treatment at the later incubation period. (3) The presence of SMX
      as a co-pollutant at concentrations of 10 and 100mg/kg removed the stimulatory
      effects of estrogens on soil DHA and significantly reduced the DHA level to below
      the level of the untreated control. SMX also depressed the appearance of
      bacterial bands that were stimulated by estrone or 17beta-estradiol alone.
      Moreover, the coexistence of SMX and estrogens induced additional bacterial
      bands, which may be tolerant strains. Overall, these results imply that the load
      of estrogens might serve as nutrient substances for soil microorganisms, whereas
      VAs as co-pollutants would cause a shift of these positive effects toward a
      significant threat to the natural soil microbial community. Therefore, the
      removal of VAs in animal waste is essential to ensure the safe use of animal
      waste in agricultural land.

PMID- 25050537
TI  - Arsenic mobility in the arsenic-contaminated Yangzonghai Lake in China.
AB  - Coagulation-precipitation techniques have been used successfully in the
      remediation of arsenic (As) contamination, but insufficient data exist to
      evaluate the side effects on lake environments (especially secondary pollution).
      Yangzonghai Lake, a deep lake located in southwest China that was treated with
      flocculants after an accident resulted in As-contamination, was selected as a
      case study. We attempted to elucidate how As migrates and transforms in the lake
      based on water simulation experiments. The results were expected to facilitate
      evaluation of the suitability and safety of the technology when used in a natural
      water body. The results showed that the As that had already been precipitated
      into the sediment by FeCl3 would be released again into the water body due to the
      increasing activity of anaerobic microorganisms, thereby causing secondary
      pollution. This phenomenon was especially evident during summer because water
      temperature stratification reduced the dissolved oxygen (DO) at the sediment
      surface and led to anaerobic conditions, which enhanced the anaerobic activity at
      the bottom of the lake. In summer, the concentration of As in the water column
      increased with increasing depth. In contrast, during winter, the concentration of
      As was quite similar at all depths of the lake because the water temperature was
      uniform during this period. As was released from sediments to the aqueous phase
      in the form of trivalent As [As(III)] upon anaerobic incubation and was oxidized
      gradually into pentavalent As [As(V)] by the higher DO in the upper layers of the
      lake water. Contrary to expectation, the disturbance (turnover in the fall) did
      not increase, but rather decreased the As concentration in the lake, which might
      result in further coagulation and precipitation through intensive mixture of the
      unsaturated flocculants from the sediments.

PMID- 25050538
TI  - Clinical- and cost-effectiveness of LDL particle-guided statin therapy: a
      simulation study.
AB  - We used the Archimedes Model, a mathematical simulation model (Model) to estimate
      the clinical- and cost-effectiveness of using LDL particle concentration (LDL-P)
      as an adjunct or alternative to LDL cholesterol (LDL-C) to guide statin therapy.
      LDL-P by NMR has been shown to be a better measure of cardiovascular disease
      (CVD) risk than LDL-C, and may therefore be a better gauge of the need for and
      response to statin treatment. Using the Model, we conducted a virtual clinical
      trial comparing the use of LDL-C alone, LDL-P alone, and LDL-C and LDL-P together
      to guide treatment in the general adult population, and in high-risk,
      dyslipidemic subpopulations. In the general population, the 5-year major adverse
      cardiovascular event (MACE) relative risk reduction (RRR) of LDL-P alone compared
      to the control arm (LDL-C alone) was 5.0% (95% CI, 4.7-5.3; p < .0001); using
      both LDL-C and LDL-P (dual markers) led to 3.0% RRR compared to the control arm
      (95% CI, 2.8-3.3; p < .0001). For individuals with diabetes, the RRR was 7.3%
      (95% CI, 6.4-8.2; p < .0001) for LDL-P alone and 6.9% for dual markers (95% CI,
      6.1-7.8; both, p < .0001). In the general population, the costs per quality
      adjusted life year (QALY) associated with the use of LDL-P alone were $76,052 at
      5 years and $8913 at 20 years and $142,825 at 5 years and $25,505 at 20 years
      with the use of both markers. In high-risk subpopulations, the use of LDL-P alone
      was cost-saving at 5 years; whereas the cost per QALY for the use of both markers
      was $14,250 at 5 years and $859 at 20 years for high-risk dyslipidemics, $19,192
      at 5 years and $649 at 20 years for diabetics, and $9030 at 5 years and $7268 at
      20 years for patients with prior CHD. In conclusion, the model estimates that
      using LDL-P to guide statin therapy may reduce the risk of CVD events to a
      greater extent than does the use of LDL-C alone and maybe cost-effective or cost
      saving for high-risk patients. 

PMID- 25050539
TI  - Differential protein expression and novel biomarkers related to 5-FU resistance
      in a 3D colorectal adenocarcinoma model.
AB  - The multicellular spheroid (MCS) is an in vitro model which is highly
      representative of the avascular region of solid tumors by reflecting
      microenvironmental conditions in vivo. Hence, it is considered the most
      appropriate model for studying drug resistance. We compared chemosensitivity to 5
      fluorouracil (5-FU) and differential protein expression between the 3D MCS model
      and the 2D monolayers using DLD-1 cells. We analyzed several significant
      signaling molecules through western blot analysis. Although various changes in
      the expression level were observed depending on the samples, we did not obtained
      remarkable findings. Notably, the level of p-mTOR decreased upon 5-FU exposure in
      the monolayers, while its level was higher in the MCSs. Nine novel proteins were
      identified by 2-DE and MALDI-TOF analysis for exhibiting differential expression
      between the MCS model and the monolayers. Among these, collapsin response
      mediator protein 2 (CRMP-2), DNA replication complex GINS protein PSF2 (PSF-2)
      and selenium-binding protein 1 (SBP-1) were notable not only for their
      differential expression but also for decreased expression following 5-FU
      exposure, indicating their possible roles as novel biomarkers for sensitivity
      (CRMP-2, PSF-2) as well as resistance (SBP-1) to 5-FU. Overall, the present study
      demonstrated greater 5-FU resistance in human colorectal cancer cells grown as
      MCSs compared to monolayers and identified p-mTOR, CRMP-2, PSF-2 and SBP-1 as
      novel potential biomarkers of 5-FU chemosensitivity/resistance for human
      colorectal cancer, findings which warrant further investigation. 

PMID- 25050540
TI  - Decellularized ovine arteries as small-diameter vascular grafts.
AB  - Atherosclerosis and its complications still represent the leading cause of death
      in the developed countries. While autologous blood vessels may be regarded as the
      best solution for peripheral and coronary bypass, they are unavailable in most
      patients. Even though tissue engineering techniques are often applied to the
      development of small-diameter vascular grafts, limiting factors of this approach
      are represented by the lack of essential extracellular matrix proteins and/or
      poor biomechanical properties of the scaffolds used. Along these lines, the aim
      of this study was to develop a decellularization protocol for ovine carotids to
      be used as suitable small-diameter vascular grafts. Samples were treated either
      with sodium dodecyl sulphate (SDS) or with Trypsin and Triton X-100; a final
      nuclease digestion was performed for both protocols. Morphological analyses
      demonstrate complete removal of nuclei and cellular components in treated
      vessels, also confirmed by significant reduction in wall thickness and DNA
      content. Essential extracellular matrix proteins such as collagen, elastin, and
      fibronectin are well preserved after decellularization. From a mechanical point
      of view, Trypsin and Triton X-100 treated arteries show elastic modules and
      compliance comparable to native carotids, whereas the use of SDS makes samples
      stiffer, with a significant decrease in the compliance mean value and an increase
      in longitudinal and circumferential Young's modules. It is demonstrated that the
      treatment where Trypsin and Triton X-100 are combined guarantees complete
      decellularization of carotids, with no significant alteration of biomechanical
      and structural properties, thus preserving a suitable environment for adhesion,
      proliferation, and migration of cells.

PMID- 25050541
TI  - Physical activity, screen time, and sitting among U.S. adolescents.
AB  - The purpose of this study was to describe self-reported levels of sitting,
      moderate- to vigorous-intensity physical activity (MVPA), television viewing, and
      computer use in a representative sample of US adolescents and to make comparisons
      between sex, race/ethnicity, weight status, and age groups. Results are based on
      3556 adolescents aged 12-19 years from the 2007-2012 National Health and
      Nutrition Examination Survey. Participants self-reported demographic, sitting,
      MVPA, television viewing (2011-2012 only) and computer use (2011-2012 only)
      variables. Height and weight were measured to calculate body mass index. On
      average, 7.5 hr/day were spent sitting and 34 median min/day were spent
      participating in MVPA, with females sitting more and participating in less MVPA
      than males across most demographic groups. Furthermore, obese males sat more and
      participated in less MVPA than nonoverweight males. Non-Hispanic white females
      participated in more MVPA than females in all other race/ethnicity groups. For
      television and computer, 38% and 22% of the sample engaged in >2 hr/day,
      respectively, and several race/ethnicity differences were observed. This study
      provides the first U.S. adolescent population estimates on self-reported sitting
      and updates population estimates on self-reported MVPA, television viewing and
      computer use. Continued efforts are needed to promote healthy active lifestyles
      in American adolescents. 

PMID- 25050542
TI  - Deficient local biological motion perception in migraineurs: results from a
      duration discrimination paradigm.
AB  - Migraine ranks as the third most common disease in the world and has caused
      significant losses of daily life abilities. Previously, people gave more
      attention to the pain of migraines and usually ignored the impairments of
      cognitive function in migraineurs. In the present study, a duration
      discrimination paradigm was used to assess the global and local biological motion
      perception in migraineurs and healthy controls. In the experiment, biological
      motion sequences and inanimate motion sequences (the inverted biological motion
      sequences) were sequentially presented on a screen. Observers were instructed to
      make a two-alternative forced choice to accurately indicate which interval (the
      first or the second) appeared longer. The stimuli involved global biological
      motion sequences and local biological motion sequences. The statistical analyses
      were conducted on the points of subjective equality that were obtained by fitting
      a psychometric function to each individual observer's data. In migraineurs,
      global biological motion signals lengthened the perceived temporal duration (as
      occurs in normal people), whereas local biological motion signals did not have
      this temporal dilation effect. The results indicated that patients with migraine
      showed a deficit in local biological motion perception, whereas their global
      biological motion perception was comparable to that of healthy subjects. 

PMID- 25050543
TI  - The distribution of transplanted human mesenchymal stem cells in the CNS of young
      Macaca fascicularis.
AB  - Mesenchymal stem cell (MSC)-based therapies have generated much hope and promise
      as a potential source of cells for cell-based therapeutic strategies in pediatric
      degenerative diseases. However, the distribution and migratory routes of MSCs are
      unknown. Here, real-time PCR and microscopy were used to observe the migration
      and distribution of labeled human MSCs (hMSCs) transplanted into the striatum of
      young Macaca fascicularis. Moreover, the differentiation of hMSCs was also
      detected using immunofluorescence. We found that hMSCs were mainly located near
      the injection site in the brain and in the anterior brain after 2 weeks. After 4
      weeks, the hMSCs had dispersed and could be detected in each brain slice and were
      more uniformly distributed than after 2 weeks. The hMSCs showed a preference for
      migration towards blood vessels, which may be one of the migratory routes used by
      hMSCs. Additionally, hMSCs could be observed to give rise to NeuN- and GFAP
      positive cells. Transplanted hMSCs also increased the expression levels of N
      cadherin in the host brain tissue, which may be one factor that drives the
      migration and differentiation of hMSCs after transplantation. These results
      provide preclinical evidence that MSC-based therapies may represent an
      efficacious alternative to more conventional treatment regimens for a variety of
      pediatric neurologic disorders. 

PMID- 25050544
TI  - Enhanced expression of hypothalamic nitric oxide synthase in rats developmentally
      exposed to organophosphates.
AB  - Nitric oxide synthase (NOS) is highly expressed in the hypothalamus, and nitric
      oxide (NO) specifically contributes to the regulation of neuronal activity within
      distinct hypothalamic regions. We studied the long-lasting effects of
      developmental exposure to low doses of organophosphate chlorpyrifos (CPF) and
      diazinon (DZN) on the expression of NOS in the hypothalamic subnuclei that
      subserve neuroendocrine, autonomic and cognitive functions. A daily dose of 1
      mg/kg of either CPF or DZN was administered to developing rats during gestational
      days 15-18 or postnatal days (PND) 1-4. Brain sections from PND 60 rats were
      processed using NADPH-diaphorase (NADPH-d) and neuronal NOS (nNOS)
      immunohistochemistry. The number of labeled neurons and the optical density (OD)
      were assessed in the supraoptic (SON), paraventricular (PVN), medial septum,
      vertical limb, and horizontal limb of the diagonal band. Developmental exposure
      to organophosphates increased the number of labeled neurons and OD in different
      subnuclei in the hypothalamus without gender selectivity. The effect on OD was
      more pronounced and was significant for more cases. Prenatal exposure to CPF and
      DZN significantly increased the OD in all regions studied with the exception of
      PVN. Neonatal exposure to DZN also consistently increased OD in all studied
      subnuclei. For rats that treated with CPF during early postnatal period, this
      effect was statistically significant only for the SON and PVN. These findings
      suggest that overexpression of NOS in the hypothalamus may contribute to the
      mechanisms inducing or compensating for endocrine, autonomic and cognitive
      abnormalities after developmental exposure to organophosphates.

PMID- 25050545
TI  - Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic
      activity and in vivo pharmacokinetics.
AB  - Meisoindigo has been a routine therapeutic agent in the clinical treatment of
      chronic myelogenous leukemia (CML) in China since the 1980s. In the present
      study, the in vitro antileukemic activity of meisoindigo was investigated in
      acute promyelocytic leukemia (APL) cells, acute myeloid leukemia (AML) cells, and
      myelomonocytic leukemia cells (NB4, NB4.007/6, HL-60 and U937) comprising both
      retinoic acid-sensitive and retinoic acid-resistant cells. We found that
      meisoindigo effectively inhibited the growth and/or proliferation of these four
      cell types at uM levels. The effects of meisoindigo in these cells are related to
      its proliferation inhibition and apoptosis induction, and are independent of cell
      cycle arrest, indicating that meisoindigo could be possible in the treatment of
      APL, AML and retinoic acid resistant APL. The in vivo pharmacokinetics of
      meisoindigo and its major circulatory metabolites in rat plasma were then
      investigated by a newly developed and validated liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method. The profiles of plasma concentration versus time
      were plotted and the relevant pharmacokinetic parameters were calculated for
      meisoindigo and its reductive metabolites. The plasma concentrations of
      meisoindigo after oral administration were much lower than the in vitro IC50s
      determined in the leukemic cells. The contradicting poor pharmacokinetic
      characteristics and the established clinical efficacy of meisoindigo could
      indicate the presence of active metabolites in vivo. 

PMID- 25050546
TI  - CNN3 regulates trophoblast invasion and is upregulated by hypoxia in BeWo cells.
AB  - CNN3 is an ubiquitously expressed F-actin binding protein, shown to regulate
      trophoblast fusion and hence seems to play a role in the placentation process. In
      this study we demonstrate that CNN3 levels are upregulated under low oxygen
      conditions in the trophoblast cell line BeWo. Since hypoxia is discussed to be a
      pro-migratory stimulus for placental cells, we examined if CNN3 is involved in
      trophoblast invasion. Indeed, when performing a matrigel invasion assay we were
      able to show that CNN3 promotes BeWo cell invasion. Moreover, CNN3 activates the
      MAPKs ERK1/2 and p38 in trophoblast cells and interestingly, both kinases are
      involved in BeWo invasion. However, when we repeated the experiments under
      hypoxic conditions, CNN3 did neither promote cell invasion nor MAPK activation.
      These results indicate that CNN3 promotes invasive processes by the stimulation
      of ERK1/2 and/or p38 under normoxic conditions in BeWo cells, but seems to have
      different functions at low oxygen levels. We further speculated that CNN3
      expression might be altered in human placentas derived from pregnancies
      complicated by IUGR and preeclampsia, since these placental disorders have been
      described to go along with impaired trophoblast invasion. Our studies show that,
      at least in our set of placenta samples, CNN3 expression is neither deregulated
      in IUGR nor in preeclampsia. In summary, we identified CNN3 as a new pro-invasive
      protein in trophoblast cells that is induced under low oxygen conditions. 

PMID- 25050547
TI  - Nuclear factor kappa-B signaling is integral to ocular neovascularization in
      ischemia-independent microenvironment.
AB  - Retinal ischemia promotes the upregulation of VEGF expression and accounts for
      most pathological features of retinal neovascularization (NV). Paradoxically,
      VEGF remains the pivotal stimulator of ocular NV, despite the absence of
      ischemia. Therefore, the central question arises as to how the various molecular
      mechanisms interplay in ischemia-independent NV. It's been suggested that
      NFkappaB plays a crucial role in the pathogenesis of diabetic vasculopathies.
      Here, we dissected the molecular mechanism of ocular NV in the rho/VEGF
      transgenic mouse model, which develops subretinal NV in ischemia-independent
      microenvironment. Furthermore, we examined whether intravitreal administration of
      YC-1, a HIF-1 inhibitor, can modulate the activation of NFkappaB and its
      downstream angiogenic signaling in the mouse retina. We demonstrated that YC-1
      inhibited retinal NFkappaB/p65 DNA binding activity and downregulated
      NFkappaB/p65, FAK, alpha5beta1, EPO, ET-1, and MMP-9 expression at the message
      and the protein levels. In addition, YC-1 significantly inhibited subretinal NV
      by reducing the number of neovascular lesions, the area of each lesion and the
      total area of NV per retina. We further investigated the influence of VEGF
      signaling pathway on HIF-1alpha transcriptional activity to substantiate that
      this mouse model develops subretinal NV in an ischemia-independent
      microenvironment. Our data demonstrated that VEGF overexpression didn't have any
      impact on HIF-1alpha transcriptional activity, whereas treatment with YC-1
      significantly inhibited endogenous HIF-1 activity. Our study suggests that
      retinal NFkappaB transcriptional activity is pivotal to ischemia-independent
      mechanisms, which lead to the local activation of angiogenic cascades. Our data
      also indicate that the nexus between VEGF and NFkappaB is implicated in
      triggering the angiogenic cascade that promotes retinal NV. Hence, targeting the
      VEGF/NFkappaB axis may act in a negative feedback loop to suppress ocular NV.
      This study suggests that inhibition of NFkappaB activation may be a means of
      turning off a "master switch" responsible for initiating and perpetuating these
      ocular pathologies. 

PMID- 25050548
TI  - A robotic approach to understanding the role and the mechanism of vicarious trial
      and-error in a T-maze task.
AB  - Vicarious trial-and-error (VTE) is a behavior observed in rat experiments that
      seems to suggest self-conflict. This behavior is seen mainly when the rats are
      uncertain about making a decision. The presence of VTE is regarded as an
      indicator of a deliberative decision-making process, that is, searching,
      predicting, and evaluating outcomes. This process is slower than automated
      decision-making processes, such as reflex or habituation, but it allows for
      flexible and ongoing control of behavior. In this study, we propose for the first
      time a robotic model of VTE to see if VTE can emerge just from a body-environment
      interaction and to show the underlying mechanism responsible for the observation
      of VTE and the advantages provided by it. We tried several robots with different
      parameters, and we have found that they showed three different types of VTE: high
      numbers of VTE at the beginning of learning, decreasing numbers afterward
      (similar VTE pattern to experiments with rats), low during the whole learning
      period, and high numbers all the time. Therefore, we were able to reproduce the
      phenomenon of VTE in a model robot using only a simple dynamical neural network
      with Hebbian learning, which suggests that VTE is an emergent property of a
      plastic and embodied neural network. From a comparison of the three types of VTE,
      we demonstrated that 1) VTE is associated with chaotic activity of neurons in our
      model and 2) VTE-showing robots were robust to environmental perturbations. We
      suggest that the instability of neuronal activity found in VTE allows ongoing
      learning to rebuild its strategy continuously, which creates robust behavior.
      Based on these results, we suggest that VTE is caused by a similar mechanism in
      biology and leads to robust decision making in an analogous way. 

PMID- 25050549
TI  - Evidence for loss of a partial flagellar glycolytic pathway during trypanosomatid
      evolution.
AB  - Classically viewed as a cytosolic pathway, glycolysis is increasingly recognized
      as a metabolic pathway exhibiting surprisingly wide-ranging variations in
      compartmentalization within eukaryotic cells. Trypanosomatid parasites provide an
      extreme view of glycolytic enzyme compartmentalization as several glycolytic
      enzymes are found exclusively in peroxisomes. Here, we characterize Trypanosoma
      brucei flagellar proteins resembling glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) and phosphoglycerate kinase (PGK): we show the latter associates with the
      axoneme and the former is a novel paraflagellar rod component. The paraflagellar
      rod is an essential extra-axonemal structure in trypanosomes and related
      protists, providing a platform into which metabolic activities can be built. Yet,
      bioinformatics interrogation and structural modelling indicate neither the
      trypanosome PGK-like nor the GAPDH-like protein is catalytically active.
      Orthologs are present in a free-living ancestor of the trypanosomatids, Bodo
      saltans: the PGK-like protein from B. saltans also lacks key catalytic residues,
      but its GAPDH-like protein is predicted to be catalytically competent. We discuss
      the likelihood that the trypanosome GAPDH-like and PGK-like proteins constitute
      molecular evidence for evolutionary loss of a flagellar glycolytic pathway,
      either as a consequence of niche adaptation or the re-localization of glycolytic
      enzymes to peroxisomes and the extensive changes to glycolytic flux regulation
      that accompanied this re-localization. Evidence indicating loss of localized ATP
      provision via glycolytic enzymes therefore provides a novel contribution to an
      emerging theme of hidden diversity with respect to compartmentalization of the
      ubiquitous glycolytic pathway in eukaryotes. A possibility that trypanosome GAPDH
      like protein additionally represents a degenerate example of a moonlighting
      protein is also discussed. 

PMID- 25050551
TI  - Nutrient addition dramatically accelerates microbial community succession.
AB  - The ecological mechanisms driving community succession are widely debated,
      particularly for microorganisms. While successional soil microbial communities
      are known to undergo predictable changes in structure concomitant with shifts in
      a variety of edaphic properties, the causal mechanisms underlying these patterns
      are poorly understood. Thus, to specifically isolate how nutrients--important
      drivers of plant succession--affect soil microbial succession, we established a
      full factorial nitrogen (N) and phosphorus (P) fertilization plot experiment in
      recently deglaciated (~3 years since exposure), unvegetated soils of the Puca
      Glacier forefield in Southeastern Peru. We evaluated soil properties and examined
      bacterial community composition in plots before and one year after fertilization.
      Fertilized soils were then compared to samples from three reference successional
      transects representing advancing stages of soil development ranging from 5 years
      to 85 years since exposure. We found that a single application of +NP fertilizer
      caused the soil bacterial community structure of the three-year old soils to most
      resemble the 85-year old soils after one year. Despite differences in a variety
      of soil edaphic properties between fertilizer plots and late successional soils,
      bacterial community composition of +NP plots converged with late successional
      communities. Thus, our work suggests a mechanism for microbial succession whereby
      changes in resource availability drive shifts in community composition,
      supporting a role for nutrient colimitation in primary succession. These results
      suggest that nutrients alone, independent of other edaphic factors that change
      with succession, act as an important control over soil microbial community
      development, greatly accelerating the rate of succession.

PMID- 25050550
TI  - Association of non-alcoholic fatty liver disease with chronic kidney disease: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a frequent, under-recognized
      condition and a risk factor for renal failure and cardiovascular disease.
      Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We
      conducted a meta-analysis to determine whether the presence and severity of NAFLD
      are associated with the presence and severity of CKD. METHODS AND FINDINGS:
      English and non-English articles from international online databases from 1980
      through January 31, 2014 were searched. Observational studies assessing NAFLD by
      histology, imaging, or biochemistry and defining CKD as either estimated
      glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were
      included. Two reviewers extracted studies independently and in duplicate.
      Individual participant data (IPD) were solicited from all selected studies.
      Studies providing IPD were combined with studies providing only aggregate data
      with the two-stage method. Main outcomes were pooled using random-effects models.
      Sensitivity and subgroup analyses were used to explore sources of heterogeneity
      and the effect of potential confounders. The influences of age, whole
      body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and
      duration of follow-up on effect estimates were assessed by meta-regression.
      Thirty-three studies (63,902 participants, 16 population-based and 17 hospital
      based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies
      (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282
      participants), we obtained IPD. NAFLD was associated with an increased risk of
      prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio
      [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was
      associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR
      2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was
      associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR
      3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the
      magnitude and direction of effects remained unaffected by diabetes status, after
      adjustment for other risk factors, and in other subgroup and meta-regression
      analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was
      positively associated with CKD stages. Limitations of analysis are the relatively
      small size of studies utilizing liver histology and the suboptimal sensitivity of
      ultrasound and biochemistry for NAFLD detection in population-based studies.
      CONCLUSION: The presence and severity of NAFLD are associated with an increased
      risk and severity of CKD. Please see later in the article for the Editors'
      Summary.

PMID- 25050552
TI  - A systematic evaluation of short tandem repeats in lipid candidate genes: riding
      on the SNP-wave.
AB  - Structural genetic variants as short tandem repeats (STRs) are not targeted in
      SNP-based association studies and thus, their possible association signals are
      missed. We systematically searched for STRs in gene regions known to contribute
      to total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels in
      two independent studies (KORA F4, n = 2553 and SAPHIR, n = 1648), resulting in 16
      STRs that were finally evaluated. In a combined dataset of both studies, the sum
      of STR alleles was regressed on each phenotype, adjusted for age and sex. The
      association analyses were repeated for SNPs in a 200 kb region surrounding the
      respective STRs in the KORA F4 Study. Three STRs were significantly associated
      with total cholesterol (within LDLR, the APOA1/C3/A4/A5/BUD13 gene region and
      ABCG5/8), five with HDL cholesterol (3 within CETP, one in LPL and one
      inAPOA1/C3/A4/A5/BUD13), three with LDL cholesterol (LDLR, ABCG5/8 and CETP) and
      two with triglycerides (APOA1/C3/A4/A5/BUD13 and LPL). None of the investigated
      STRs, however, showed a significant association after adjusting for the lead or
      adjacent SNPs within that gene region. The evaluated STRs were found to be well
      tagged by the lead SNP within the respective gene regions. Therefore, the STRs
      reflect the association signals based on surrounding SNPs. In conclusion, none of
      the STRs contributed additionally to the SNP-based association signals identified
      in GWAS on lipid traits. 

PMID- 25050554
TI  - The accuracy of the new landmark using respiratory jugular venodilation and
      direct palpation in right internal jugular vein access.
AB  - BACKGROUND: Although ultrasonography is recommended in internal jugular vein
      (IJV) catheterization, the landmark-guided technique should still be considered.
      The central landmark using the two heads of the sternocleidomastoid muscle is
      widely used, but it is inaccurate for IJV access. As an alternative landmark, we
      investigated the accuracy of the new landmark determined by inspection of the
      respiratory jugular venodilation and direct IJV palpation in right IJV access by
      ultrasonography. METHODS AND FINDINGS: Thirty patients were enrolled. After
      induction of anesthesia, the central landmark was marked at the cricoid cartilage
      level (M1) and the alternative landmark determined by inspection of the
      respiratory jugular venodilation and direct palpation of IJV was also marked at
      the same level (M2). Using ultrasonography, the location of IJV was identified
      (M3) and the distance between M1 and M3 as well as between M2 and M3 were
      measured. The median (interquartile range) distance between the M2 and M3 was 3.5
      (2.0-6.0) mm, compared to 17.5 (12.8-21.3) mm between M1 and M3. (P<0.001) The
      dispersion of distances between M2 and M3 was significantly smaller than between
      M1 and M3. (P<0.001) The visibility of respiratory jugular venodilation was
      associated with CVP more than 4 mmHg. Limitations of the present study are that
      the inter-observer variability was not investigated and that the visibility of
      the alternative landmark can be limited to right IJV in adults. CONCLUSION: The
      alternative landmark may allow shorter distance for the right side IJV access
      than the central landmark and can offer advantages in right IJV catheterization
      when ultrasound device is unavailable. TRIAL REGISTRATION: Clinical Research
      Informational Service KCT0000812.

PMID- 25050555
TI  - Expansion of IgG+ B-cells during mitogen stimulation for memory B-cell ELISpot
      analysis is influenced by size and composition of the B-cell pool.
AB  - The memory B-cell (MBC) ELISpot assay is the main technique used to measure
      antigen-specific MBCs as a readout of humoral immune memory. This assay relies on
      the ability of MBCs to differentiate into antibody-secreting cells (ASC) upon
      polyclonal stimulation. The total number of IgG+ ASCs generated by mitogen
      stimulation is often used as a reference point; alternatively antigen-specific
      MBCs are expressed as a frequency of post-culture peripheral blood mononuclear
      cells (PBMC) as a surrogate for absolute frequencies. Therefore, it is important
      to know whether IgG+ B-cells are uniformly expanded during the preceding mitogen
      culture as a true reflection of MBC frequencies ex vivo. We systematically
      compared B-cell phenotype and proportions before and after mitogen stimulation in
      cultures of 269 peripheral blood mononuclear cell samples from 62 volunteers by
      flow cytometry and analyzed the number of resulting ASCs. Our data show that the
      number of total IgG+ ASCs detected by ELISpot after mitogen stimulation
      correlates with the proportion of IgG+ MBCs ex vivo, highlighting its general
      robustness for comparisons of study cohorts at group level. The expansion of
      total and IgG+ B-cells during mitogen-stimulation, however, was not identical in
      all cultures, but influenced by size and composition of the ex vivo B-cell
      compartment. The uncorrected readout of antigen-specific MBCs per million post
      culture PBMCs therefore only preserves the quality, but not the magnitude of
      differences in the ex vivo MBC response between groups or time points,
      particularly when comparing samples where the B-cell compartment substantially
      differs between cohorts or over time. Therefore, expressing antigen-specific
      cells per total IgG+ ASCs is currently the best measure to correct for mitogen
      culture effects. Additionally, baseline information on the size and composition
      of the ex vivo B-cell compartment should be supplied to additionally inform about
      differences or changes in the size and composition of the ex vivo MBC
      compartment. 

PMID- 25050556
TI  - Porous silk scaffolds for delivery of growth factors and stem cells to enhance
      bone regeneration.
AB  - Stem cell-based tissue engineering shows promise for bone regeneration and
      requires artificial microenvironments to enhance the survival, proliferation and
      differentiation of the seeded cells. Silk fibroin, as a natural protein polymer,
      has unique properties for tissue regeneration. The present study aimed to
      evaluate the influence of porous silk scaffolds on rat bone marrow stem cells
      (BMSCs) by lenti-GFP tracking both in vitro and in vivo in cranial bone defects.
      The number of cells seeded within silk scaffolds in rat cranial bone defects
      increased from 2 days to 2 weeks after implantation, followed by a decrease at
      eight weeks. Importantly, the implanted cells survived for 8 weeks in vivo and
      some of the cells might differentiate into endothelial cells and osteoblasts
      induced by the presence of VEGF and BMP-2 in the scaffolds to promote
      angiogenesis and osteogenesis. The results demonstrate that porous silk scaffolds
      provide a suitable niche to maintain long survival and function of the implanted
      cells for bone regeneration. 

PMID- 25050557
TI  - The cytotoxic role of RREB1, ZIP3 zinc transporter, and zinc in human pancreatic
      adenocarcinoma.
AB  - Pancreatic cancer (ductal adenocarcinoma) remains a deadly cancer with ~85%
      mortality, and a 5-year survival rate of ~6% or less for the past 30 years. The
      factors and events associated with the development of pancreatic cancer are
      poorly identified. As such, effective biomarkers for early detection of
      malignancy are lacking. Efficacious chemotherapy once the cancer is identified
      does not exist. Recent clinical studies have revealed that the zinc levels are
      consistently and markedly decreased in adenocarcinoma as compared with
      normal/benign pancreatic tissue. The decreased zinc is exhibited in well
      differentiated malignancy and in progressing malignancy, and also exists
      throughout the development of PanIN. Concurrent with the decrease in zinc, RREB1
      transcription factor and ZIP3 zinc uptake transporter are downregulated. Thus, a
      RREB1/ZIP3/Zinc transformation appears to be an early event in the development of
      pancreatic cancer. We propose that this transformation is necessary to prevent
      the accumulation of high cellular zinc levels, which result in cytotoxic effects
      on the developing malignant cells. This report now demonstrates that exposure of
      Panc1 cells to physiological concentrations of zinc that result in increased zinc
      uptake and accumulation also inhibits cell proliferation. The study further shows
      that ZIP3 is the important transporter required for the accumulation of zinc and
      its inhibition of proliferation. RREB1 is identified as the positive regulator of
      ZIP3 expression. Therefore, the pathway of RREB1/ZIP3/Zinc and its downregulation
      during oncogenesis exist to prevent the accumulation of cytotoxic levels of zinc
      during the development and progression of the malignant cells in pancreatic
      adenocarcinoma. 

PMID- 25050559
TI  - Young Adults' Implicit and Explicit Attitudes towards the Sexuality of Older
      Adults.
AB  - Sexual interest and capacity can extend far into later life and result in many
      positive health outcomes. Yet there is little support for sexual expression in
      later life, particularly among young adults. This study assessed and compared
      young adults' explicit and implicit attitudes towards older adult sexuality. A
      sample of 120 participants (18-24 years; 58% female) completed a self-report
      (explicit) measure and a series of Implicit Association Tests capturing attitudes
      towards sexuality among older adults. Despite reporting positive explicit
      attitudes, young people revealed an implicit bias against the sexual lives of
      older adults. In particular, young adults demonstrated implicit biases favouring
      general, as compared to sexual, activities and young adults as compared to older
      adults. Moreover, the bias favouring general activities was amplified with regard
      to older adults as compared to younger adults. Our findings challenge the
      validity of research relying on self-reports of attitudes about older adult
      sexuality.

PMID- 25050560
TI  - Systematic review of clinical judgment and reasoning in nursing.
AB  - A systematic review was conducted to examine the findings on clinical judgment
      and reasoning in nursing that have emerged since Tanner's review in 2006.
      Electronic databases were searched to locate primary research studies about
      clinical judgment and reasoning in nursing. Fifteen studies were extracted and
      analyzed using the five main conclusions outlined by Tanner. The findings of the
      systematic review generally support Tanner's original model, although the role of
      experience in clinical reasoning and judgment is still not well understood or
      fully established. In recent literature, researchers have furthered their
      knowledge by using tools for improving these skills in both nursing students and
      practicing nurses, although no one strategy has been identified as being more
      effective. This is reflected in the consideration of a sixth conclusion on
      clinical judgment and reasoning in nursing-education strategies to improve
      clinical judgment may influence what a nurse brings to the situation.

PMID- 25050561
TI  - Teaching differential diagnosis to nurse practitioner students in a distance
      program.
AB  - An interactive case study (ICS) is a novel way to enhance the teaching of
      differential diagnosis to distance learning nurse practitioner students. Distance
      education renders the use of many teaching strategies commonly used with face-to
      face students difficult, if not impossible. To meet this new pedagogical dilemma
      and to provide excellence in education, the ICS was developed. Kolb's theory of
      experiential learning supported efforts to follow the utilization of the ICS.
      This study sought to determine whether learning outcomes for the distance
      learning students were equivalent to those of on-campus students who engaged in a
      live-patient encounter. Accuracy of differential diagnosis lists generated by
      onsite and online students was compared. Equivalency testing assessed clinical,
      rather than only statistical, significance in data from 291 students. The ICS
      responses from the distance learning and onsite students differed by 4.9%, which
      was within the a priori equivalence estimate of 10%. Narrative data supported the
      findings.

PMID- 25050562
TI  - Hiring and incorporating doctor of nursing practice-prepared nurse faculty into
      academic nursing programs.
AB  - Semistructured interviews were conducted with 15 deans and directors of nursing
      programs across the United States to gain an understanding of how Doctor of
      Nursing Practice (DNP)-prepared nurses seeking academic positions are hired and
      used in schools of nursing. Interviews sought to gain information regarding (a)
      differences and similarities in the roles and responsibilities of DNP- and Doctor
      of Philosophy (PhD)-prepared faculty, (b) educational advancement and mentoring
      of DNP-prepared nurse faculty, (c) recruitment of doctorally prepared nurse
      faculty, and (d) shortages of nursing faculty. DNP- and PhD-prepared nurse
      faculty are hired for varying roles in baccalaureate and higher degree schools of
      nursing, some similar to other faculty with master's degrees and others similar
      to those with PhDs; in associate degree in nursing programs, they are largely
      hired for the same type of work as nurse faculty with master's degrees.
      Regardless of program or degree type, the main role of DNP-prepared faculty is
      teaching.

PMID- 25050558
TI  - Rare mutations in RINT1 predispose carriers to breast and Lynch syndrome-spectrum
      cancers.
AB  - Approximately half of the familial aggregation of breast cancer remains
      unexplained. A multiple-case breast cancer family exome-sequencing study
      identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present
      in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del
      (p.M378del), and c.1207G>T (p.D403Y). On the basis of this finding, a population
      based case-control mutation-screening study was conducted that identified 29
      carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23
      in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched
      controls [OR, 3.24; 95% confidence interval (CI), 1.29-8.17; P = 0.013]. RINT1
      mutation screening of probands from 798 multiple-case breast cancer families
      identified four additional carriers of rare genetic variants. Analysis of the
      incidence of first primary cancers in families of women carrying RINT1 mutations
      estimated that carriers were at increased risk of Lynch syndrome-spectrum cancers
      [standardized incidence ratio (SIR), 3.35; 95% CI, 1.7-6.0; P = 0.005],
      particularly for relatives diagnosed with cancer under the age of 60 years (SIR,
      10.9; 95% CI, 4.7-21; P = 0.0003). SIGNIFICANCE: The work described in this study
      adds RINT1 to the growing list of genes in which rare sequence variants are
      associated with intermediate levels of breast cancer risk. Given that RINT1 is
      also associated with a spectrum of cancers with mismatch repair defects, these
      findings have clinical applications and raise interesting biological questions.

PMID- 25050563
TI  - Clinical research education: perspectives of nurses, employers, and educators.
AB  - The aim of this study was to understand the current environment around clinical
      research relating to nursing education and practice. This descriptive study
      analyzed data from 33 in-depth interviews with faculty members, nurse executives,
      staff development directors, and practicing nurses, as well as an online
      interactive brainstorming session with 28 deans of schools of nursing (or their
      designee). Patterns and themes that emerged within each group were identified and
      analyzed in relation to study objectives. Central themes emerged around
      participants' knowledge and attitudes about clinical research education for
      baccalaureate nursing students, factors enhancing or inhibiting inclusion of
      clinical research content in baccalaureate nursing programs, and professional
      roles nursing students could expect to assume after graduation. Although the
      participants agreed that mastery of clinical research knowledge and related
      skills is important, there was no agreement whether nurses should receive this
      education and training in baccalaureate programs or in staff development.

PMID- 25050564
TI  - Resveratrol inhibits proliferation in human colorectal carcinoma cells by
      inducing G1/S-phase cell cycle arrest and apoptosis through caspase/cyclin-CDK
      pathways.
AB  - The present study compared the effect of resveratrol on HCT116 and Caco-2 human
      colon cancer cells. Annexin V/propidium iodide staining, MTT assay and western
      blot analysis revealed that resveratrol induced cycle arrest in the two cell
      lines, which was evidenced by cell cycle analysis and changes in the expression
      of the cell cycle proteins cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1,
      proliferating cell nuclear antigen and P21. Furthermore, resveratrol was found to
      have a strong apoptosis-inducing effect, which was evidenced through the high
      percentage of annexin V positive cells and high protein expression of cleaved
      caspase-7, cleaved-caspase-9 and cleaved-poly(ADP-ribose) polymerase in the
      resveratrol-treated cancer cells. In conclusion, these results demonstrated that
      resveratrol had greater growth inhibitory and cell cycle arrest effects on Caco-2
      cells than HCT116 cells, through caspase-dependent and cyclin-CDK pathways.

PMID- 25050565
TI  - Histone deacetylase 5 promotes the proliferation of glioma cells by upregulation
      of Notch 1.
AB  - Histone deacetylases (HDACs) constitute a family of enzymes that play important
      roles in the epigenetic regulation of gene expression and contribute to the
      growth, differentiation and apoptosis of cancer cells. However, the biological
      function of HDAC5 in glioma cells has not been fully understood. In the present
      study, we found that the mRNA and protein levels of HDAC5 are increased in human
      glioma tissues and cell lines. In addition, overexpression of HDAC5 promoted
      proliferation of glioma cells, as measured by the MTT assay. By contrast, HDAC5
      gene silencing using small interfering RNA (siRNA) inhibited cell proliferation.
      Furthermore, we demonstrated that HDAC5 enhances Notch 1 expression at both the
      mRNA and the protein level in glioma cell lines. Taken together, these results
      demonstrated, for the first time to the best of our knowledge, that HDAC5
      promotes glioma cell proliferation, and suggest that this effect involves the
      upregulation of Notch 1. Therefore, our study may provide a novel therapeutic
      target for treatment of gliomas.

PMID- 25050566
TI  - Cochlear implantation and single-sided deafness.
AB  - PURPOSE OF REVIEW: Recently, more patients with single-sided deafness (SSD) have
      been undergoing cochlear implantation. We review recent studies and case reports
      to provide an overview of the efficacy of cochlear implants to rehabilitate
      patients with SSD with regards to sound localization, speech discrimination, and
      tinnitus suppression. RECENT FINDINGS: There are a growing number of studies
      evaluating the effect of cochlear implantation for rehabilitation of the deficits
      associated with SSD over the past several years as more centers offer this
      treatment modality to patients with SSD. Although individual studies have few
      patients and are underpowered, the vast majority report improvement in sound
      localization, speech understanding in quiet and noise, and tinnitus. In some
      cases, the outcomes with cochlear implant appear superior to those achieved with
      other devices, including contralateral routing of sound devices and
      osseointegrated implants. SUMMARY: Although cochlear implant is not a Food and
      Drug Administration-approved treatment for SSD, several recent studies show
      improvements in speech understanding, sound localization, and tinnitus. Because
      of the low number of cases, it is difficult to conclusively compare outcomes
      achieved with cochlear implants and those provided by other devices. However, on
      the basis of encouraging early results and the unique ability to restore binaural
      sound processing, a growing number of centers offer cochlear implants as
      treatment for SSD. Forthcoming studies will help define outcome expectations in
      different populations.

PMID- 25050567
TI  - Plasma proteomic changes during hypothermic and normothermic cardiopulmonary
      bypass in aortic surgeries.
AB  - Deep hypothermic circulatory arrest (DHCA) is a protective method against brain
      ischemia in aortic surgery. However, the possible effects of DHCA on the plasma
      proteins remain to be determined. In the present study, we used novel high
      throughput technology to compare the plasma proteomes during DHCA (22C) with
      selective cerebral perfusion (SCP, n=7) to those during normothermic
      cardiopulmonary bypass (CPB, n=7). Three plasma samples per patient were obtained
      during CPB: T1, prior to cooling; T2, during hypothermia; T3, after rewarming for
      the DHCA group and three corresponding points for the normothermic group. A
      proteomic analysis was performed using isobaric tag for relative and absolute
      quantification (iTRAQ) labeling tandem mass spectrometry to assess quantitative
      protein changes. In total, the analysis identified 262 proteins. The
      bioinformatics analysis revealed a significant upregulation of complement
      activation at T2 in normothermic CPB, which was suppressed in DHCA. These
      findings were confirmed by the changes of the terminal complement complex (SC5b
      9) levels. At T3, however, the level of SC5b-9 showed a greater increase in DHCA
      compared to normothermic CPB, while 48 proteins were significantly downregulated
      in DHCA. The results demonstrated that DHCA and rewarming potentially exert a
      significant effect on the plasma proteome in patients undergoing aortic surgery.

PMID- 25050571
TI  - Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue
      Carcinogenesis.
AB  - Despite widening interest in the possible association between infection/
      inflammation and cancer development, knowledge of this issue in relation to oral
      cancer remains inadequate. This study aimed to determine the susceptibility of
      Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing
      inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4
      NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation
      in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23
      females) rats received drinking water with or without 4-NQO (20 ppm) for eight
      weeks. Histopathological and immunohistochemical analyses of the tongue were
      performed at week 20. Additionally, the mRNA expression of inflammatory cytokines
      in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma
      (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of
      gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats
      than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the
      female KAD rats was significantly greater than that observed in the male KAD (p <
      0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the
      mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated
      female KAD rats were the highest among the rats given 4-NQO. These results show
      that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue
      carcinogenesis, suggesting the utility of models employing KAD rats for
      investigating the pathobiology of oral (tongue) carcinogenesis associated with
      inflammation. 

PMID- 25050572
TI  - Clinical assessment of auto-positive end-expiratory pressure by diaphragmatic
      electrical activity during pressure support and neurally adjusted ventilatory
      assist.
AB  - BACKGROUND: Auto-positive end-expiratory pressure (auto-PEEP) may substantially
      increase the inspiratory effort during assisted mechanical ventilation. Purpose
      of this study was to assess whether the electrical activity of the diaphragm
      (EAdi) signal can be reliably used to estimate auto-PEEP in patients undergoing
      pressure support ventilation and neurally adjusted ventilatory assist (NAVA) and
      whether NAVA was beneficial in comparison with pressure support ventilation in
      patients affected by auto-PEEP. METHODS: In 10 patients with a clinical suspicion
      of auto-PEEP, the authors simultaneously recorded EAdi, airway, esophageal
      pressure, and flow during pressure support and NAVA, whereas external PEEP was
      increased from 2 to 14 cm H2O. Tracings were analyzed to measure apparent
      "dynamic" auto-PEEP (decrease in esophageal pressure to generate inspiratory
      flow), auto-EAdi (EAdi value at the onset of inspiratory flow), and IDEAdi
      (inspiratory delay between the onset of EAdi and the inspiratory flow). RESULTS:
      The pressure necessary to overcome auto-PEEP, auto-EAdi, and IDEAdi was
      significantly lower in NAVA as compared with pressure support ventilation,
      decreased with increase in external PEEP, although the effect of external PEEP
      was less pronounced in NAVA. Both auto-EAdi and IDEAdi were tightly correlated
      with auto-PEEP (r = 0.94 and r = 0.75, respectively). In the presence of auto
      PEEP at lower external PEEP levels, NAVA was characterized by a characteristic
      shape of the airway pressure. CONCLUSIONS: In patients with auto-PEEP, NAVA,
      compared with pressure support ventilation, led to a decrease in the pressure
      necessary to overcome auto-PEEP, which could be reliably monitored by the
      electrical activity of the diaphragm before inspiratory flow onset (auto-EAdi).

PMID- 25050573
TI  - Compressive forces and computed tomography-derived positive end-expiratory
      pressure in acute respiratory distress syndrome.
AB  - BACKGROUND: It has been suggested that higher positive end-expiratory pressure
      (PEEP) should be used only in patients with higher lung recruitability. In this
      study, the authors investigated the relationship between the recruitability and
      the PEEP necessary to counteract the compressive forces leading to lung collapse.
      METHODS: Fifty-one patients with acute respiratory distress syndrome (7 mild, 33
      moderate, and 11 severe) were enrolled. Patients underwent whole-lung computed
      tomography (CT) scan at 5 and 45 cm H2O. Recruitability was measured as the
      amount of nonaerated tissue regaining inflation from 5 to 45 cm H2O. The
      compressive forces (superimposed pressure) were computed as the density times the
      sternum-vertebral height of the lung. CT-derived PEEP was computed as the sum of
      the transpulmonary pressure needed to overcome the maximal superimposed pressure
      and the pleural pressure needed to lift up the chest wall. RESULTS: Maximal
      superimposed pressure ranged from 6 to 18 cm H2O, whereas CT-derived PEEP ranged
      from 7 to 28 cm H2O. Median recruitability was 15% of lung parenchyma
      (interquartile range, 7 to 21%). Maximal superimposed pressure was weakly related
      with lung recruitability (r = 0.11, P = 0.02), whereas CT-derived PEEP was
      unrelated with lung recruitability (r = 0.0003, P = 0.91). The maximal
      superimposed pressure was 12 +/- 3, 12 +/- 2, and 13 +/- 1 cm H2O in mild,
      moderate, and severe acute respiratory distress syndrome, respectively, (P =
      0.0533) with a corresponding CT-derived PEEP of 16 +/- 5, 16 +/- 5, and 18 +/- 5
      cm H2O (P = 0.48). CONCLUSIONS: Lung recruitability and CT scan-derived PEEP are
      unrelated. To overcome the compressive forces and to lift up the thoracic cage, a
      similar PEEP level is required in higher and lower recruiters (16.8 +/- 4 vs.
      16.6 +/- 5.6, P = 1).

PMID- 25050574
TI  - Still looking for best PEEP.

PMID- 25050575
TI  - Results for a series of 697 arteriovenous malformations treated by gamma knife:
      influence of angiographic features on the obliteration rate.
AB  - BACKGROUND: Stereotactic radiosurgery (RS) is an effective tool in treating brain
      arteriovenous malformations (AVMs). Careful study of AVM angiographic
      characteristics may improve results. OBJECTIVE: To report the long-term outcomes
      of Gamma Knife RS (GKRS) in brain AVMs, focusing on how the angioarchitectural
      and hemodynamic parameters of AVMs affect the post-RS results. METHODS: This was
      a retrospective, longitudinal study of 697 consecutive GKRS treatments of brain
      AVMs in 662 patients performed at a single center between 1993 and 2005. The mean
      age of the patients was 37 years; the median AVM volume was 3.6 cm(3); and the
      mean follow-up was 11 years. Forty-five percent of patients presented with
      intracranial hemorrhage; 44% underwent embolization; and 7% had multiple RSs. AVM
      characteristics in the RS-planning angiograms were analyzed, and their
      relationship to the post-RS obliteration rate was determined by univariate and
      multivariate analyses. RESULTS: The obliteration rate after a single RS was
      69.3%; after multiple RS, it was 75%. Positive predictors of obliteration
      included compact nidus (odds ratio = 3.16; 95% confidence interval, 1.92-5.22),
      undilated feeders (odds ratio = 0.36; 95% confidence interval, 0.23-0.57),
      smaller AVM volume (odds ratio = 0.95; 95% confidence interval, 0.92-0.99), and
      higher marginal dose (odds ratio = 1.16; 95% confidence interval, 1.06-1.27).
      Improvement or clinical stability was observed in 89.3% of patients;
      postprocedural bleeding was noted in 6.1%; and clinical worsening attributable to
      RS was seen in 3.8%. The annual risk of hemorrhage in the 4 years after RS was
      1.2%. CONCLUSION: GKRS yielded a good long-term clinical outcome in most
      patients. Certain angiographic features of brain AVMs such as a well-defined
      nidus and undilated feeder arteries contribute to AVM occlusion by RS. GKRS can
      be regarded as the treatment of choice for AVMs <6 cm(3), even after bleeding.

PMID- 25050576
TI  - Evidence-based assessment of well-established interventions: the parachute and
      the epidural hematoma.
AB  - BACKGROUND: The methods of evidence-based medicine are a relatively recent
      development in the understanding of clinical practice. They are criticized as not
      providing support for interventions long held to be highly effective based on
      experience that predated the availability of evidence-based analysis. OBJECTIVE:
      To determine if the methods of evidence-based medicine can be successfully
      applied to interventions established before those methods were developed.
      METHODS: Systematic review of English language literature on the natural history
      and treated prognosis of acute epidural hematoma and analysis of existing data on
      mortality associated with parachute use. DATA SOURCES: Sources of data included
      Medline, Old Medline, Science Citation Index, British and US Parachute
      Associations, and Federal Aviation Administration and National Transportation
      Safety Board databases (both of the United States). Also included were national
      databases reporting mortality and total number of parachute uses. RESULTS: The
      estimated mortality of falling from an airplane with an ineffective parachute is
      74% (69-79). Mortality associated with effective parachute deployment is between
      0.0011% and 0.0017%. For acute epidural hematoma, estimated mortality is 98.54%
      (95.1-99.9) without treatment and 12.9% (10.5-15.3) with treatment. The number
      needed to treat to prevent 1 death for the parachute is estimated to be 1.35
      (1.27-1.45) and for epidural hematoma 1.17 (1.13-1.22) (95% binomial confidence
      intervals in parentheses). CONCLUSION: The methods of evidence-based medicine are
      robust and can deal with interventions of great face validity and those
      considered well established before such methods were well developed. We propose
      initial criteria for evaluating the quality of evidence supporting long
      established interventions.

PMID- 25050577
TI  - Mixed reality ventriculostomy simulation: experience in neurosurgical residency.
AB  - BACKGROUND: Medicine and surgery are turning toward simulation to improve on
      limited patient interaction during residency training. Many simulators today use
      virtual reality with augmented haptic feedback with little to no physical
      elements. In a collaborative effort, the University of Florida Department of
      Neurosurgery and the Center for Safety, Simulation & Advanced Learning
      Technologies created a novel "mixed" physical and virtual simulator to mimic the
      ventriculostomy procedure. The simulator contains all the physical components
      encountered for the procedure with superimposed 3-D virtual elements for the
      neuroanatomical structures. OBJECTIVE: To introduce the ventriculostomy simulator
      and its validation as a necessary training tool in neurosurgical residency.
      METHODS: We tested the simulator in more than 260 residents. An algorithm
      combining time and accuracy was used to grade performance. Voluntary
      postperformance surveys were used to evaluate the experience. RESULTS: Results
      demonstrate that more experienced residents have statistically significant better
      scores and completed the procedure in less time than inexperienced residents.
      Survey results revealed that most residents agreed that practice on the simulator
      would help with future ventriculostomies. CONCLUSION: This mixed reality
      simulator provides a real-life experience, and will be an instrumental tool in
      training the next generation of neurosurgeons. We have now implemented a standard
      where incoming residents must prove efficiency and skill on the simulator before
      their first interaction with a patient.

PMID- 25050579
TI  - Deep brain stimulation for obsessive-compulsive disorder: systematic review and
      evidence-based guideline sponsored by the American Society for Stereotactic and
      Functional Neurosurgery and the Congress of Neurological Surgeons (CNS) and
      endorsed by the CNS and American Association of Neurological Surgeons.
AB  - BACKGROUND: It is estimated that 40% to 60% of patients with obsessive-compulsive
      disorder (OCD) continue to experience symptoms despite adequate medical
      management. For this population of treatment-refractory patients, promising
      results have been reported with the use of deep brain stimulation (DBS).
      OBJECTIVE: To conduct a systematic review of the literature and develop evidence
      based guidelines on DBS for OCD. METHODS: A systematic literature search was
      undertaken using the PubMed database for articles published between 1966 and
      October 2012 combining the following words: "deep brain stimulation and obsessive
      compulsive disorder" or "electrical stimulation and obsessive-compulsive
      disorder." Of 353 articles, 7 were retrieved for full-text review and analysis.
      The quality of the articles was assigned to each study and the strength of
      recommendation graded according to the guidelines development methodology of the
      American Association of Neurological Surgeons/Congress of Neurological Surgeons
      Joint Guidelines Committee. RESULTS: Of the 7 studies, 1 class I and 2 class II
      double-blind, randomized, controlled trials reported that bilateral DBS is more
      effective in improving OCD symptoms than sham treatment. CONCLUSION: Based on the
      data published in the literature, the following recommendations can be made: (1)
      There is Level I evidence, based on a single class I study, for the use of
      bilateral subthalamic nucleus DBS for the treatment of medically refractory OCD.
      (2) There is Level II evidence, based on a single class II study, for the use of
      bilateral nucleus accumbens DBS for the treatment of medically refractory OCD.
      (3) There is insufficient evidence to make a recommendation for the use of
      unilateral DBS for the treatment of medically refractory OCD.

PMID- 25050580
TI  - Somatosensory evoked potential changes in neuroendovascular procedures: incidence
      and association with clinical outcome in 873 patients.
AB  - BACKGROUND: Neurophysiological monitoring is routinely used during neurosurgical
      procedures. Use of neurophysiological monitoring has extended to
      neuroendovascular procedures, but evidence of its impact on clinical outcome in
      this arena is limited. OBJECTIVE: To report the incidence of significant
      intraoperative somatosensory evoked potential (SSEP) changes during
      neuroendovascular surgery and to correlate SSEP changes with clinical outcomes.
      METHODS: Patients who underwent neuroendovascular surgery at our institution
      between 2011 and 2013 were included in the analysis. Medical charts and imaging
      studies were reviewed retrospectively for sex, age, lesion type and size,
      clinical presentation, type of endovascular procedure, duration of SSEP change,
      reversibility of SSEP change, incidence of intraoperative complications and
      related mortalities, presence of new infarction within 72 hours of intervention,
      and discharge outcome. RESULTS: Of 873 consecutive patients, 52 (6%) had
      clinically significant intraoperative SSEP changes. Twenty-four patients (46%)
      had SSEP changes that were corrected, and 28 patients (54%) had changes that were
      not reversed before the end of surgery. Both decreased duration and reversal of
      SSEP changes were associated with a lower incidence of postoperative infarction
      and more favorable clinical outcome on discharge. The positive predictive value
      of an irreversible SSEP change for postoperative infarction in our study was 21%,
      and the negative predictive value was 83%. CONCLUSION: The approximate incidence
      of SSEP changes is 6% during neuroendovascular procedures. Rapid reversal of SSEP
      changes is associated with better outcomes. SSEP monitoring may be a valuable
      tool for preventing complications after neuroendovascular interventions.

PMID- 25050581
TI  - Frameless stereotactic drilling for placement of depth electrodes in refractory
      epilepsy: operative technique and initial experience.
AB  - BACKGROUND: For stereotactic implantation of depth electrodes in refractory
      epilepsy, both frame-based and frameless techniques have been developed. The
      higher versatility of current frameless techniques compared with framed-based
      methods is paid by the need of a standard burr hole for the implantation of 1
      electrode. OBJECTIVE: To develop a frameless method that allows convenient
      implantation of the electrode via a percutaneous bolt as used in frame-based
      methods, thereby avoiding the need for a standard burr hole. METHODS: We adopted
      our technique from frameless stereotactic biopsy and designed the GIDE, a bone
      fixated Guide for Implantation of Depth Electrodes. This reducing sleeve works as
      a stabilizer of the neuronavigation arm through bony contact and allows
      percutaneous stereotactic drilling, screwing of an implantation bolt, and
      placement of the depth electrode. RESULTS: Twenty-six electrodes in 7 patients (5
      male and 2 female patients; median age, 19.6 years; range, 5.5-39.1 years) were
      successfully implanted. The overall accuracy was comparable to that of frameless
      stereotactic biopsy with a target deviation of 3.0+/-1.9 mm (mean+/-SD). All
      electrodes were within or touched the targeted anatomic structure with an
      adequate quality of the recordings. We encountered no hemorrhage or neurological
      deficit related to the depth electrode. CONCLUSION: Our technique combines the
      high versatility of frameless stereotaxy with the convenient implantation and
      fixation of the depth electrode via a percutaneous bolt used in frame-based
      stereotactic methods. Thus, our technique allows fast, efficient implantation of
      depth electrodes for intracranial electroencephalography recordings.

PMID- 25050582
TI  - Surgery of intradural extramedullary tumors: retrospective analysis of 107 cases.
AB  - BACKGROUND: Intradural extramedullary tumors (IDEMTs) are uncommon lesions that
      cause pain and neurological deficits. OBJECTIVE: To evaluate the effects of
      surgery for IDEMTs. METHODS: This cohort study recruited all patients operated on
      for IDEMTs at the Department of Neurology and Psychiatry of Sapienza University
      of Rome from January 2003 to January 2013. The analysis was conducted on clinical
      records evaluation over a 1-year follow-up. The Graphic Rating Scale was used to
      assess pain. Neurological deficits were detected through neurological
      examination. Quality of life was evaluated with the EuroQol (EQ-5D). Statistical
      interpretation of the data was performed with SPSS version 19 software. RESULTS:
      One hundred seven patients were recruited. Three were lost to follow-up. Patients
      reported lower level of pain 1 year after surgery (before surgery, 6.05; after
      surgery, 3.65). Mean comparison showed a significant decrease of -2.400 (P <
      .001). Ninety-two patients (88.5%) were neurologically asymptomatic 1 year after
      surgery. Only 12 patients (11.5%) presented with a deficit, with a global
      decrease of 39% (chi(2) = 27.6; P < .005). The quality of life in patients was
      middle to high (mean rating of EQ-5D visual analog score, 61.78%). The lowest
      levels of quality of life were found in patients with sphincter dysfunctions
      (mean, 33.4). CONCLUSION: Surgery for IDEMTs has a good outcome. Patients
      reported lower levels of pain and a drastic reduction in neurological symptoms 1
      year after surgery. The quality of life is middle to high. It is influenced
      mainly by the neurological outcome.

PMID- 25050583
TI  - Multimodality monitoring, inflammation, and neuroregeneration in subarachnoid
      hemorrhage.
AB  - BACKGROUND: Stroke, including subarachnoid hemorrhage (SAH), is one of the
      leading causes of morbidity and mortality worldwide. The mortality rate of poor
      grade SAH ranges from 34% to 52%. In an attempt to improve SAH outcomes, clinical
      research on multimodality monitoring has been performed, as has basic science
      research on inflammation and neuroregeneration (which can occur due to injury
      induced neurogenesis). Nevertheless, the current literature does not focus on the
      integrated study of these fields. Multimodality monitoring corresponds to
      physiological data obtained during clinical management by both noninvasive and
      invasive methods. Regarding inflammation and neuroregeneration, evidence suggests
      that, in all types of stroke, a proinflammatory phase and an anti-inflammatory
      phase occur consecutively; these phases affect neurogenesis, which is also
      influenced by other pathophysiological features of stroke, such as ischemia,
      seizures, and spreading depression. OBJECTIVE: To assess whether injury-induced
      neurogenesis is a prognostic factor in poor-grade SAH that can be monitored and
      modulated. METHODS: We propose a protocol for multimodality monitoring-guided
      hypothermia in poor-grade SAH in which cellular and molecular markers of
      inflammation and neuroregeneration can be monitored in parallel with clinical and
      multimodal data. EXPECTED OUTCOMES: This study may reveal correlations between
      markers of inflammation and neurogenesis in blood and cerebrospinal fluid, based
      on clinical and multimodality monitoring parameters. DISCUSSION: This protocol
      has the potential to lead to new therapies for acute, diffuse, and severe brain
      diseases.

PMID- 25050584
TI  - Correspondence: obituary, Charles A. Fager, MD.

PMID- 25050585
TI  - Anterolateral transcavernous extradural petrosectomy approach: 3-dimensional
      operative video demonstration in cadavers.

PMID- 25050586
TI  - KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer
      detected by colonoscopy.
AB  - Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Adenoma is
      the main precursor lesion and, recently, the serrated polyps were described as a
      group of colorectal lesions with malignant potential. The morphologic and
      biologic characterizations of serrated polyps remain limited. The aim of the
      present study was to determine the frequency of KRAS and BRAF mutations and
      microsatellite instability (MSI) in CRC precursor lesions, to evaluate the
      association between molecular, pathologic and morphologic alterations in
      precursor lesions and to compare with the alterations detected in CRC. A series
      of 342 precursor lesions were removed from 155 patients during colonoscopy. After
      morphologic classification, molecular analysis was performed in 103 precursor
      lesions, and their genetic profile compared with 47 sporadic CRCs. Adenomas were
      the main precursor lesions (70.2%). Among the serrated polyps, the main precursor
      lesion was hyperplastic polyps (HPs) (82.4%), followed by sessile serrated
      adenomas (12.7%) and traditional serrated adenomas (2.0%). KRAS mutations were
      detected in 13.6% of the precursor lesions, namely in adenomas and in HPs, but in
      no serrated adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions,
      mainly associated with serrated polyps and absent in adenomas (P<0.001). High MSI
      (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited
      KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role
      of KRAS and BRAF mutations in CRC carcinogenesis, a crucial step in implementing
      CRC screening strategies. 

PMID- 25050587
TI  - Social stress, economic hardship, and psychological distress as predictors of
      sustained abstinence from substance use after treatment.
AB  - Social characteristics associated with disadvantage, such as racial/ethnic
      minority status, female gender, and low socioeconomic status (SES), are often
      associated with increased psychological distress and substance use disorders.
      This project tests a conceptual model derived from Pearlin's social stress theory
      for predicting abstinence from substance use between baseline and 1-year follow
      up in secondary data from a large statewide sample of Kentucky substance abuse
      treatment participants (N = 1,123). Racial minority status, employment, and
      higher education level were predictive of substance use at follow-up, while
      female gender was predictive of abstinence. Limitations, implications for
      practice, and suggestions for future research are discussed. 

PMID- 25050588
TI  - A mixed treatment comparison of gabapentin enacarbil, pramipexole, ropinirole and
      rotigotine in moderate-to-severe restless legs syndrome.
AB  - OBJECTIVE: A mixed treatment comparison (MTC) was performed to investigate the
      relative efficacy and safety of licensed pharmaceuticals for moderate-to-severe
      restless legs syndrome (RLS). METHODS: RLS trials published over the past 10
      years were identified via systematic literature searches of MEDLINE, Embase,
      Cochrane CENTRAL, and manufacturers' websites. MTC was performed with WinBUGS
      software using a Bayesian approach. Identified primary outcomes: change in
      International RLS Study Group Rating Scale (IRLS) at week 12 and end of
      maintenance (EoM). SECONDARY OUTCOMES: IRLS and Clinical Global Impression -
      Improvement Scale (CGI-I) responders, RLS-6 items and adverse events (AEs).
      RESULTS: Twenty-eight clinical trials were identified. Fifteen were included in
      the primary analysis. Indirect comparisons were established among gabapentin
      enacarbil, pramipexole, ropinirole, rotigotine and placebo. Overall, the four
      active treatments showed similar efficacies as assessed by changes in IRLS
      scores, IRLS responders, CGI-I responders, and RLS-6 scores. The sole exception
      was change in IRLS at week 12, for which rotigotine was likely more efficacious
      than ropinirole (mean difference: -2.52 [95% CrI: -4.74, -0.40]). Indirect
      comparisons on safety endpoints indicated ropinirole was associated with a higher
      risk of nausea than the other agents, and was more likely to result in
      discontinuations due to lack of efficacy than pramipexole. Nausea was likely more
      frequent with pramipexole than gabapentin enacarbil, and rotigotine was more
      likely to result in discontinuation due to AEs than ropinirole and pramipexole.
      CONCLUSIONS: This MTC confirmed the superiority of gabapentin enacarbil,
      pramipexole, ropinirole, and rotigotine above placebo in alleviating RLS
      symptoms. Compared to ropinirole, rotigotine showed some additional benefit in
      terms of change in IRLS at Week 12. Choice of RLS drugs requires careful
      evaluation of effectiveness and safety profiles in clinical practice. Due to lack
      of head-to-head trials, inconsistency could not be assessed in our analysis. Head
      to-head trials on a more homogeneous population are needed to validate the MTC
      results.

PMID- 25050589
TI  - Efficacy and safety of low-dose submicron diclofenac for the treatment of
      osteoarthritis pain: a 12 week, phase 3 study.
AB  - OBJECTIVE: NSAIDs, such as diclofenac, are the most commonly used medications to
      treat osteoarthritis (OA), but they are associated with dose-related adverse
      events (AEs). Low-dose submicron diclofenac was developed using a new,
      proprietary dry milling process that creates submicron drug particles (SoluMatrix
      Fine Particle Technology * ), enabling effective treatment at lower doses than
      other commercially available diclofenac drug products. This phase 3 study
      evaluated the efficacy and safety of low-dose submicron diclofenac 35 mg three
      times daily (tid) and twice daily (bid) in patients with OA pain. RESEARCH DESIGN
      AND METHODS: This double-blind study enrolled patients >=40 years of age with
      clinically and radiographically confirmed (Kellgren-Lawrence grade II-III) hip or
      knee OA. Eligible patients were chronic NSAID and/or acetaminophen (APAP) users
      with baseline Western Ontario and McMasters Universities Osteoarthritis Index
      (WOMAC) pain subscale scores >=40 mm by visual analog scale and an OA flare (>=15
      mm increase in WOMAC pain subscale score following discontinuation of NSAIDs/APAP
      at screening). Patients were randomized to submicron diclofenac 35 mg tid,
      submicron diclofenac 35 mg bid, or placebo for 12 weeks. ClinicalTrials.gov
      identifier: NCT01461369. MAIN OUTCOME MEASURES: Efficacy parameters included mean
      change from baseline in WOMAC pain subscale score at week 12 (primary efficacy
      parameter) and in average total WOMAC score over 12 weeks. RESULTS: Submicron
      diclofenac 35 mg tid significantly improved WOMAC pain subscale scores from
      baseline at 12 weeks (-44.1; p = 0.0024) compared with placebo (-32.5). Submicron
      diclofenac 35 mg bid provided numerical improvement in pain at week 12 that did
      not reach statistical significance (-39.0; p = 0.0795) compared with placebo.
      Submicron diclofenac 35 mg tid (-35.9; p = 0.0002) and 35 mg bid (-30.3; p =
      0.0363) improved the average total WOMAC score in treated patients over 12 weeks
      compared with placebo (-23.2). The most frequent AEs in the submicron diclofenac
      treated groups were diarrhea, headache, nausea, and constipation. The inclusion
      of patients with a documented requirement for analgesic therapy (OA 'flare') at
      baseline and the high rates of rescue medication usage in the placebo group may
      have impacted the study outcome for the submicron diclofenac treatment groups.
      CONCLUSIONS: Low-dose submicron diclofenac is an effective therapeutic option for
      the treatment of OA pain.

PMID- 25050590
TI  - Efficacy and safety of local anesthetics bupivacaine, ropivacaine and
      levobupivacaine in combination with sufentanil in epidural anesthesia for labor
      and delivery: a meta-analysis.
AB  - BACKGROUND: In epidural analgesia, synthetic opioids increase the potency of
      amide local anesthetics by modifying their analgesic properties. The purpose of
      this systematic review and meta-analysis is to compare the efficacy and safety of
      bupivacaine with ropivacaine and levobupivacaine in combination with sufentanil
      (BUPI-, ROPI-, and LBUPI-SUF respectively) in epidural analgesia for labor.
      METHODS: A literature search was made in multiple electronic databases for
      original research papers published between 1995 and 2014. Meta-analyses were
      based on mean differences between the groups as well as odds ratios where
      appropriate. Both the fixed effects and random effects models were utilized and
      heterogeneity was tested with the I(2) index. RESULTS: Analgesia duration was
      significantly longer in ROPI-SUF and LBUPI-SUF than in BUPI-SUF administered
      women with a mean difference (95% CI) of 16.12 (2.56, 29.68); P < 0.03 and 18.02
      (9.09, 26.96); P < 0.0001 respectively under a random effects model (REM).
      Effective analgesia achievement was significantly earlier in the BUPI-SUF than in
      either the ROPI-SUF (2.61 [1.87, 3.36]; P < 0.00001) or the LBUPI-SUF groups
      (4.53 [3.66, 5.40]; P < 0.00001) under a fixed effects model (FEM) but not under
      a REM (I(2 )= 85%). Motor blockade incidence was higher in BUPI-SUF anesthetized
      patients, although the difference was not statistically significant. A higher
      incidence of instrumental deliveries was evident in the ROPI-SUF (FEM: 1.68
      [1.13, 2.50]; P < 0.02/REM: 1.76 [1.00, 3.11]; P = 0.05) and LBUPI-SUF (FEM: 2.03
      [1.07, 3.86]; P < 0.04/REM: 2.03 [1.07, 3.86]; P < 0.04) groups than in the BUPI
      SUF group of patients. Inconsistencies in the availability of parametric data and
      use of slightly varying anesthetic dosages in included studies were important
      limitations. CONCLUSION: Whereas significantly longer labor analgesia can be
      achieved with ROPI-SUF and LBUPI-SUF and ropivacaine is associated with
      comparatively less motor blockade, labor duration after epidural analgesia has
      been found to be shorter in BUPI-SUF and there is a low incidence of instrumental
      delivery.

PMID- 25050591
TI  - Infliximab efficacy in rheumatoid arthritis after an inadequate response to
      etanercept or adalimumab: results of a target-driven active switch study.
AB  - OBJECTIVE: Evaluate efficacy of infliximab with response-driven dosing in
      patients with active RA. RESEARCH DESIGN AND METHODS: Patients (n = 203) with
      active RA despite methotrexate + etanercept/adalimumab, participated in this
      active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6,
      14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks
      14 and 22. The primary endpoint was EULAR response at Week 10. Safety was
      assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI)
      were measured at Weeks 0, 6, 14, and 26. CLINICAL TRIAL REGISTRATION: NCT
      00714493, EudraCT 2007-003288-36. RESULTS: Of 197 evaluable patients, 120/77
      previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender
      joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was
      6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved
      EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change 
      1.1 [1.15]; p < 0.001). EULAR response was achieved by 41.7%/62.3% of patients
      previously receiving etanercept/adalimumab (p = 0.006). At Week 26, 51.8% (95%
      CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab
      dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week
      26. Median serum concentration levels at Week 26 showed that dose escalation
      helped EULAR non-responders achieve levels similar to or higher than the levels
      seen in responders. ATI were associated with lower serum concentrations of
      infliximab, consistent with lower efficacy rates among ATI-positive patients.
      CONCLUSION: Infliximab, in treat-to-target settings with individual dose
      escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients
      switched to infliximab after inadequate response to etanercept/adalimumab. The
      observed efficacy indicated that the switch to infliximab and ability to increase
      dose in a targeted fashion were beneficial. KEY LIMITATIONS: Given the relatively
      short duration of study follow-up, these safety findings require confirmation in
      a longer-term study.

PMID- 25050592
TI  - Clinical evaluation of the first oxycodone once daily prolonged release tablet in
      moderate to severe chronic pain: a randomized, double-blind, multicenter, cross
      over, non-inferiority study to investigate efficacy and safety in comparison with
      an established oxycodone twice daily prolonged release tablet.
AB  - OBJECTIVE: The first oxycodone once daily (OOD) has been developed and after
      successful pharmacokinetic characterization, therapeutic efficacy and safety were
      compared to an established oxycodone twice daily (OTD: Oxygesic/OxyContin,
      Mundipharma). DESIGN AND METHODS: A randomized, double-blind, multicenter, cross
      over, non-inferiority study was conducted in patients (n = 68) with chronic
      malignant or non-malignant pain. The new OOD was compared to OTD at identical
      total daily doses (TDD: 40-120 mg/day) employing intensive, five times daily
      current pain (0-100 mm visual analog scale, VAS) and twice daily 12 h recalled
      pain assessments as well as safety parameters such as nausea and sedation (VAS)
      over 5 days for each treatment (after a 5 day run-in phase). RESULTS: There was
      no significant difference in analgesic potency detected between the two
      treatments based on 95% CI for difference in the daily mean current pain (-2.09
      mm VAS) over 5 days, determined as -5.09 to 0.91 mm VAS. A difference <=12 mm VAS
      indicated non-inferiority of OOD, i.e. lack of clinically relevant difference in
      analgesia. Intake of rescue medication had no effect on study results as
      evaluated by ANCOVA. The difference in adverse events (AEs) between the two
      treatments did not reach significance, as 19.1% and 23.5% of patients experienced
      treatment-related AEs while on OOD and OTD, respectively. Advantages for OOD
      regarding consistency of analgesia (i.e. use of rescue medication, current and
      recalled pain) and sedation did not reach statistical significance in this
      limited study population. CONCLUSION: Despite the small number of patients and
      short study duration, the results support the conclusion that new OOD is (at
      least) equivalent to established OTD regarding safety and efficacy.

PMID- 25050593
TI  - Increased salt intake during early ontogenesis lead to development of arterial
      hypertension in salt-resistant Wistar rats.
AB  - A direct relationship exists between salt consumption and hypertension. Increased
      sodium intake does not automatically lead to a rise in blood pressure (BP)
      because of marked intra-individual variability in salt sensitivity. Wistar rats
      are a salt-resistant strain and increased salt intake in adults does not induce
      hypertension. Mechanisms regulating BP develop during early ontogenesis and
      increased sodium consumption by pregnant females leads to an increase in BP of
      their offspring, but early postnatal stages have not been sufficiently analyzed
      in salt-resistant strains of rats. The aim of this work was to study the effects
      of increased salt during early ontogeny on cardiovascular characteristics of
      Wistar rats. We used 16 control (C; 8 males + 8 females) rats fed with a standard
      diet (0.2% sodium) and 16 experimental (S; 8 males + 8 females) rats fed with a
      diet containing 0.8% sodium. BP was measured weekly and plasma renin activity,
      aldosterone and testosterone concentrations were assayed by radioimmunoassay
      after the experiment in 16-week-old animals. In the kidney, AT1 receptors were
      determined by the western blot. BP was higher in the S as compared with the C
      rats and did not differ between males and females. The relative left ventricle
      mass was increased in S as compared with C males and no differences were recorded
      in females. No significant differences between groups were found in hormonal
      parameters and AT1 receptors. Results indicate that moderately increased salt
      intake during postnatal ontogeny results in a BP rise even in salt-resistant
      rats. 

PMID- 25050594
TI  - The effect of beclometasone dipropionate/formoterol extra-fine fixed combination
      on the peripheral airway inflammation in controlled asthma.
AB  - BACKGROUND: Suppression of small airway inflammation may contribute to achieving
      asthma control. We aimed to evaluate the additional effect of beclometasone
      dipropionate/formoterol (BDP/F) hydrofluoroalkane (HFA) pressurized metered dose
      inhaler (pMDI) (BDP/F-HFA 100/6 MUg pMDI) on airway inflammation and functional
      parameters in asthma cases, who were optimally controlled by maintenance therapy.
      METHODS: Ninety-five controlled asthmatic patients were included. They were
      grouped as Group 1 [budesonide/formoterol 320/9 MUg dry powder inhaler (DPI)] and
      Group 2 (fluticasone/salmeterol 500/50 MUg DPI) according to the combination they
      used. Then Group 3 was established by random selection from these two groups, and
      BDP/F-HFA 100/6 MUg pMDI treatment was prescribed. All patients were evaluated in
      the beginning of the study and were re-evaluated at the end of a 3-week treatment
      period by spirometry, exhaled nitric oxide (eNO) levels, and small airway
      functional indices, namely, Sacin and Scond values. RESULTS: There was no
      significant statistical difference in terms of age, height, weight, disease
      duration, symptoms, and spirometric parameters between the groups. There was a
      significant decrease in eNO levels in asthma cases who were on BDP/F-HFA therapy
      (p=0.001). A significant improvement in Sacin values at the end of the treatment
      period was observed in cases treated with BDP/F-HFA (p=0.001), indicating that
      inflammation was suppressed in peripheral airways. CONCLUSIONS: These results
      emphasize that asthma treatment has mainly focused on the strategy to keep the
      disease under control; maintaining optimal functional level might be
      underestimated. BDP/F-HFA may have an additional favorable effect on the
      peripheral airway inflammation in the controlled asthma.

PMID- 25050595
TI  - A combined therapeutic regimen of buspirone and environmental enrichment is more
      efficacious than either alone in enhancing spatial learning in brain-injured
      pediatric rats.
AB  - Buspirone, a 5-HT1A receptor agonist, and environmental enrichment (EE) enhance
      cognition and reduce histopathology after traumatic brain injury (TBI) in adult
      rats, but have not been fully evaluated after pediatric TBI, which is the leading
      cause of death in children. Hence, the aims of this study were to assess the
      efficacy of buspirone alone (Experiment 1) and in combination with EE (Experiment
      2) in TBI postnatal day-17 male rats. The hypothesis was that both therapies
      would confer cognitive and histological benefits when provided singly, but their
      combination would be more efficacious. Anesthetized rats received a cortical
      impact or sham injury and then were randomly assigned to receive intraperitoneal
      injections of buspirone (0.08 mg/kg, 0.1 mg/kg, and 0.3 mg/kg) or saline vehicle
      (1.0 mL/kg) 24 h after surgery and once daily for 16 days (Experiment 1). Spatial
      learning and memory were assessed using the Morris water maze (MWM) on post
      operative days 11-16, and cortical lesion volume was quantified on day 17. Sham
      controls for each condition were significantly better than all TBI groups. In the
      TBI groups, buspirone (0.1 mg/kg) enhanced MWM performance versus vehicle and
      buspirone (0.08 mg/kg and 0.3 mg/kg) (p<0.05) and reduced lesion volume relative
      to vehicle (p=0.038). In Experiment 2, buspirone (0.1 mg/kg) or vehicle was
      combined with EE after TBI, and the data were compared to the standard (STD)
      housed groups from Experiment 1. EE lead to a significant enhancement of spatial
      learning and a reduction in lesion size versus STD. Moreover, the combined
      treatment group (buspirone+EE) performed markedly better than the buspirone+STD
      and vehicle+EE groups, which suggests an additive effect and supports the
      hypothesis. The data replicate previous studies assessing these therapies in
      adult rats. These novel findings may have important rehabilitation-relevant
      implications for clinical pediatric TBI.

PMID- 25050596
TI  - Topical photodynamic therapy induces systemic immunosuppression via generation of
      platelet-activating factor receptor ligands.

PMID- 25050597
TI  - beta2-adrenoceptor activation modulates skin wound healing processes to reduce
      scarring.
AB  - During wound healing, excessive inflammation, angiogenesis, and differentiated
      human dermal fibroblast (HDF ) function contribute to scarring, whereas
      hyperpigmentation negatively affects scar quality. Over 100 million patients heal
      with a scar every year. To investigate the role of the beta 2 adrenergic receptor
      (beta2AR) in wound scarring, the ability of beta 2 adrenergic receptor agonist
      (beta2ARag) to alter HDF differentiation and function, wound inflammation,
      angiogenesis, and wound scarring was explored in HDFs, zebrafish, chick
      chorioallantoic membrane assay (CAM), and a porcine skin wound model,
      respectively. Here we identify a beta2AR-mediated mechanism for scar reduction.
      beta2ARag significantly reduced HDF differentiation, via multiple cAMP and/or
      fibroblast growth factor 2 or basic FGF (FGF2)-dependent mechanisms, in the
      presence of transforming growth factor betabeta1, reduced contractile function,
      and inhibited mRNA expression of a number of profibrotic markers. beta2ARag also
      reduced inflammation and angiogenesis in zebrafish and CAMs in vivo,
      respectively. In Red Duroc pig full-thickness wounds, beta2ARag reduced both scar
      area and hyperpigmentation by almost 50% and significantly improved scar quality.
      Indeed, mechanisms delineated in vitro and in other in vivo models were evident
      in the beta2ARag-treated porcine scars in vivo. Both macrophage infiltration and
      angiogenesis were initially decreased, whereas DF function was impaired in the
      beta2ARag-treated porcine wound bed. These data collectively reveal the potential
      of beta2ARag to improve skin scarring. 

PMID- 25050599
TI  - CD90(+) human dermal stromal cells are potent inducers of FoxP3(+) regulatory T
      cells.
AB  - The skin has to effectively combat external attacks, while maintaining skin
      immune homeostasis under steady-state conditions. To fulfill these challenging
      tasks, the dermis harbors a variety of heterogeneous cell types that are able to
      suppress T-cell proliferation similar to bone marrow mesenchymal stromal cells.
      Here we show that plastic-adherent, human dermal cells induce FoxP3 expression in
      TCR-complex-stimulated CD25(-)CD4(+)CD45RA(+) T cells in the absence of CD28 co
      ligation in a cell-contact-dependent manner. These FoxP3(+) T cells reveal an
      effective suppressive capacity in vitro. Moreover, we found that the vast
      majority of CD90(+) dermal cells are perivascularly located and generate a
      significantly higher percentage of regulatory T cells compared with cells
      expressing markers such as CD271 in vitro. Importantly, we further demonstrate
      that plastic-adherent dermal cells are also able to differentiate toward the
      endothelial lineage. Our data show that human skin harbors specific cell types
      with immunosuppressive potential, which are located in close vicinity to their
      likely operational area and provide evidence for a CD28-independent regulatory
      mechanism. Further, the differentiation potential into endothelial cells suggests
      the existence of a tissue-resident cell pool for vessel regeneration. These
      findings might have important implications for the clinical use of allogeneic
      dermal cells to rebuild an imbalanced human skin immune homeostasis. 

PMID- 25050600
TI  - Multiple self-healing palmoplantar carcinoma: a familial predisposition to skin
      cancer with primary palmoplantar and conjunctival lesions.

PMID- 25050601
TI  - Seeking systemic change: risk and protective factors affecting low-income urban
      youth.
AB  - This themed issue presents five articles tackling the topic of risk and
      protective processes affecting children and adolescents living in urban poverty.
      Through their research, the authors seek understanding of the particular
      challenges that low-income urban youth face, with the ultimate goal of
      understanding how best to intervene at various levels of the ecological system.
      Within this broad theme, studies examine specific stressors, mediators, and
      moderators that impact the mental health of youth living in urban poverty. The
      final article presents a data-driven, community-based intervention for this
      population. 

PMID- 25050598
TI  - Suppressing AP1 factor signaling in the suprabasal epidermis produces a
      keratoderma phenotype.
AB  - Keratodermas comprise a heterogeneous group of highly debilitating and painful
      disorders characterized by thickening of the skin with marked hyperkeratosis.
      Some of these diseases are caused by genetic mutation, whereas other forms are
      acquired in response to environmental factors. Our understanding of signaling
      changes that underlie these diseases is limited. In the present study, we
      describe a keratoderma phenotype in mice in response to suprabasal epidermis
      specific inhibition of activator protein 1 transcription factor signaling. These
      mice develop a severe phenotype characterized by hyperplasia, hyperkeratosis,
      parakeratosis, and impaired epidermal barrier function. The skin is scaled,
      constricting bands encircle the tail and digits, the footpads are thickened and
      scaled, and loricrin staining is markedly reduced in the cornified layers and
      increased in the nucleus. Features of this phenotype, including nuclear loricrin
      localization and pseudoainhum (autoamputation), are characteristic of the
      Vohwinkel syndrome. We confirm that the phenotype develops in a loricrin-null
      genetic background, indicating that suppressed suprabasal AP1 factor function is
      sufficient to drive this disease. We also show that the phenotype regresses when
      suprabasal AP1 factor signaling is restored. Our findings suggest that
      suppression of AP1 factor signaling in the suprabasal epidermis is a key event in
      the pathogenesis of keratoderma. 

PMID- 25050602
TI  - Depressive symptoms in young, urban schoolchildren: environmental, social, and
      cognitive risk.
AB  - This study examined relations among stressors, perceived social competence,
      attributional style, and depressive symptoms in young urban schoolchildren. Data
      were collected from 85 5- to 11-year-olds, mostly African American, who attended
      a public elementary school in a low-income urban area. Social competence was
      examined as a potential mediator, and attributional style was examined as a
      potential moderator of the relation between stressful life events and depressive
      symptoms. Separate analyses were conducted by age and gender. For older children
      and girls, main effects were found for stressful life events as predictors of
      depressive symptoms. Mediational analyses indicated that perceived peer
      acceptance served as a mediator of the relation between stressful life events and
      depressive symptoms for girls. In addition, attributional style moderated the
      relation between stressors and depressive symptoms in the older children.
      Together, findings suggest that significant relations exist among stressful life
      events, social and cognitive processes, and depressive symptoms in young urban
      children and that these relations are influenced by gender and development. 

PMID- 25050603
TI  - Depressive symptoms in low-income, urban adolescents: cognitive and contextual
      factors.
AB  - This study examined the relationships among cognitive variables, family
      immigration history, negative life events, and depressive symptoms in a sample of
      306 low-income, urban fifth- and sixth-grade children. Explanatory style and
      negative automatic thoughts were the cognitive variables examined. There were
      three key findings. First, children who were immigrants reported significantly
      more depressive symptoms, more negative life events, and more negative automatic
      thoughts than children who were not immigrants. Second, both explanatory style
      and negative automatic thoughts were significantly associated with depressive
      symptoms above and beyond the effects of child immigration history and negative
      life events. Finally, negative automatic thoughts mediated the relationship
      between child immigration history and depressive symptoms. We discuss the
      clinical and research implications of these findings. 

PMID- 25050604
TI  - Stressful life experiences and peer externalizing behaviors mediate the relation
      between reduced family support and externalizing symptoms in low-income urban
      youth.
AB  - Family support, urban stressors, and peer behavior were examined in relation to
      externalizing symptoms in 605 predominantly low-income urban sixth through eighth
      grade adolescents. Mother and father support were each associated with lower
      levels of externalizing symptoms in both males and females. For males, father
      absence was associated with increased peer externalizing behavior and heightened
      rates of youth externalizing symptoms. Stress (in the form of major life events,
      daily hassles, and exposure to violence) and peer externalizing behavior were
      examined as mediators of the relation between parent support and youth
      externalizing symptoms. Increased stress exposure mediated the relation between
      weak mother and father support and youth externalizing symptoms. Additionally,
      for females, peer externalizing behavior mediated the relation between weak
      mother support and youth externalizing symptoms. 

PMID- 25050605
TI  - The influence of nondisclosure on the mental health of urban African-American
      adolescents exposed to community violence.
AB  - African-American youth residing in urban poverty have been shown to be at
      increased risk for exposure to violence and internalizing symptoms, but there has
      been little investigation of moderating processes that might attenuate or
      exacerbate this association. The current study examined nondisclosure as a
      possible moderator of the association between community violence and
      internalizing symptoms with a sample of 152 low-income urban African-American
      early adolescents using hierarchical regression analyses. Results revealed that
      nondisclosure for relationship reasons (e.g., adults could not be trusted to
      provide needed support) moderated the association between exposure to community
      violence and internalizing symptoms. Unexpectedly, however, results of simple
      effects analyses revealed a stronger association between exposure to violence and
      internalizing symptoms for youth who disclosed more to adults. Although
      unexpected, this pattern builds upon prior research indicating that adult-child
      relationships are compromised within the context of urban poverty and that
      protective factors may lose their power under conditions of extreme stress. 

PMID- 25050606
TI  - Development of cities mentor project: an intervention to improve academic
      outcomes for low-income urban youth through instruction in effective coping
      supported by mentoring relationships and protective settings.
AB  - This manuscript summarizes an iterative process used to develop a new
      intervention for low-income urban youth at risk for negative academic outcomes
      (e.g., disengagement, failure, drop-out). A series of seven steps, building
      incrementally one upon the other, are described: 1) identify targets of the
      intervention; 2) develop logic model; 3) identify effective elements of targets;
      4) vet intervention with stakeholders; 5) develop models for sustaining the
      intervention; 6) develop measures of relevant constructs currently missing from
      the literature; 7) assess feasibility and usability of the intervention. Methods
      used to accomplish these steps include basic research studies, literature
      reviews, meta-analyses, focus groups, community advisory meetings, consultations
      with scholarly consultants, and piloting. The resulting intervention provides
      early adolescents in low-income urban communities with a) training in
      contextually relevant coping, b) connection to mentors who support youth's
      developing coping strategies, and c) connection to youth-serving community
      organizations, where youth receive additional support. 

PMID- 25050607
TI  - Association between quality of end-of-life care and possible complicated grief
      among bereaved family members.
AB  - BACKGROUND: Little is known about the association between quality of end-of-life
      care of a patient and complicated grief among bereaved family members. OBJECTIVE:
      This study aims to examine the impact of quality of end-of-life care on
      complicated grief among bereaved family members in a Japanese general population
      sample. METHODS: A mail-based cross-sectional questionnaire survey was used. A
      total of 641 individuals aged 40 to 79 years in the general population who lost
      their loved one within the period between 6 months and 10 years were enrolled.
      Complicated grief was assessed using the Brief Grief Questionnaire, and the
      bereaved family members' perceptions on quality of end-of-life care were assessed
      using the Care Evaluation Scale and the Good Death Inventory. Logistic regression
      analysis was used to identify the variables that associated with possible
      complicated grief. RESULTS: Possible complicated grief was observed in 24.5% of
      the participants. Three components of quality of end-of-life care, namely,
      dissatisfaction with the explanation to the family about the patient's expected
      outcome, unreasonable cost of care, and family's perception that the deceased
      person had not achieved a sense of completion about his or her life, were
      significantly associated with possible complicated grief. Spousal relationship,
      primary caregiver, and high psychological distress also had significant
      association. CONCLUSIONS: Perceptions on quality of end-of-life care were
      significantly associated with complicated grief. Providing sufficient information
      to patients' family about expected outcome and enhancing patients' sense of
      completion about their life may prevent bereaved family members from developing
      complicated grief.

PMID- 25050608
TI  - Histone deacetylase inhibitors induce attenuation of Wnt signaling and TCF7L2
      depletion in colorectal carcinoma cells.
AB  - Histone deacetylase inhibitors (HDIs) specifically affect cancer cells by
      inducing cell cycle arrest, activate apoptotic pathways and re-activate
      epigenetically silenced tumor suppressor genes, but their pleiotropic mode of
      action is not fully understood. Despite the clinical effects of HDIs in the
      treatment of hematological malignancies, their potency against solid tumors is
      still unclear. We investigated the effects and mechanisms of HDI action in
      colorectal carcinoma cell lines with an activated Wnt signaling pathway, which is
      implicated in different aspects of tumorigenesis, including cell proliferation,
      apoptosis, angiogenesis and metastasis. We assessed the effects of HDI treatment
      in colorectal carcinoma cell lines by measuring histone hyperacetylation, cell
      viability and expression of Wnt target genes. Upon treatment with HDIs of the
      hydroxamate class, we found attenuation of Wnt signaling with concomitant
      induction of apoptosis and colorectal cancer cell death. Strikingly, the effects
      of HDIs on Wnt signaling were independent of histone hyperacetylation, thus we
      investigated the role of non-histone target proteins of histone deacetylases
      (HDACs). The compounds TSA and SAHA induced a rapid proteasome-dependent
      depletion of the Wnt transcription factor TCF7L2, which may be mediated by
      inhibition of HDAC 6 and 10. Our findings provide a molecular rationale for the
      use of HDIs against colorectal carcinomas with activated Wnt signaling. 

PMID- 25050609
TI  - High plasma thiocyanate levels are associated with enhanced myeloperoxidase
      induced thiol oxidation and long-term survival in subjects following a first
      myocardial infarction.
AB  - Elevated levels of myeloperoxidase (MPO) are associated with poor cardiovascular
      outcomes. MPO uses H2O2 to generate oxidants including HOCl and HOSCN, from
      chloride and thiocyanate (SCN(-)) ions, respectively. SCN(-) is the preferred
      substrate. Elevation of this anion decreases HOCl generation and increases HOSCN
      formation, a thiol-specific oxidant. Such changes are of potential relevance to
      people with elevated SCN(-) levels, such as smokers. In this retrospective study,
      we examined whether elevated plasma MPO and SCN(-) levels increased thiol
      oxidation as a result of increased HOSCN formation, and impacted on long-term
      survival in 176 subjects (74 non-smokers, 46 smokers, and 56 previous smokers)
      hospitalized after a first myocardial infarction. Plasma thiols were not
      significantly altered in smokers compared to non-smokers or past smokers.
      However, significant positive correlations were detected between SCN(-) levels
      and MPO-induced thiol loss in the total population (r = 0.19, P = 0.020) and
      smokers alone (r = 0.58, P < 0.0001). Twelve-year all-cause mortality data
      indicate that above median MPO is significantly associated with higher mortality,
      but below-median MPO and above-median SCN(-) results in increased survival,
      compared to below-median SCN(-). Cox proportional hazard analysis showed a
      significant decrease in mortality for each 1 MUM increase in SCN(-) (0.991; P =
      0.040). Subject age was, as expected, a strong predictor of subject survival.
      Overall these data suggest that subjects with below-median MPO and above-median
      SCN(-) have better long-term survival, and that elevated plasma levels of SCN(-)
      might be protective in at least some populations.

PMID- 25050610
TI  - Vitamin D supplementation and upper respiratory tract infections in adolescent
      swimmers: a randomized controlled trial.
AB  - Observational studies identified associations between vitamin D insufficiency
      (serum 25(OH)D < 30ng.ml-1) and risk of upper respiratory infection (URI).
      Swimmers are highly prone to URIs, which might hinder their performance. The aim
      of this study was to examine if vitamin D3 supplementation reduces URI burden in
      vitamin D-insufficient swimmers. Fifty-five competitive adolescent swimmers with
      vitamin D insufficiency were randomized to receive vitamin D3 (2,000IU.d-1) or
      placebo for 12 winter weeks. A URI symptom questionnaire was completed weekly.
      Serum 25(OH)D concentrations were measured by radio-immunoassay before and after
      supplementation. We used linear regression to examine the relation between the
      change in 25(OH)D concentrations during the trial, and the duration and severity
      of URIs. There were no between-group differences in the frequency, severity, or
      duration of URIs. Exploratory analyses revealed that in the placebo group only,
      the change in 25(OH)D concentrations during the trial was highly associated with
      the duration of URIs (r = -0.90,p < .001), and moderately associated with the
      severity of URIs (r = -0.65,p = .043). The between-group differences for duration
      were highly significant. Vitamin D3 supplementation in adolescent swimmers with
      vitamin D insufficiency did not reduce URI burden. However, larger decreases in
      serum 25(OH)D concentrations were associated with significantly longer and more
      severe URI episodes. 

PMID- 25050612
TI  - Physisorption and chemisorption of a self-assembled monolayer by the quartz
      crystal microbalance.
AB  - A new adsorption model was developed to investigate the adsorption process of
      SAMs in the gaseous scenario, and the results were verified by using a prototype
      quartz crystal microbalance (QCM) sensor. In the experimental study, the observed
      properties in the gaseous scenario did not conform to the conventional theories
      well but matched the proposed adsorption model better. Hence, an optimal
      methodology for the theoretical study of adsorption process of SAMs was
      developed. The conventional adsorption model of Langmuir is suitable only for the
      fast initial adsorption step (i.e., physisorption) in the process of forming SAMs
      in the liquid scenario. Here, the rates of adsorption and desorption (ka, kd) at
      different temperatures were investigated. The activation barrier Ea = 59.738
      kJ/mol was obtained by the Arrhenius equation. The result agreed well with that
      obtained experimentally. More importantly, this study has established a new
      avenue of QCM chip applications. 

PMID- 25050611
TI  - Osteochondral defect repair using a polyvinyl alcohol-polyacrylic acid (PVA-PAAc)
      hydrogel.
AB  - Poly(vinyl alcohol) (PVA) hydrogels can be candidates for articular cartilage
      repair due to their high water content. We synthesized a PVA-poly(acrylic acid)
      (PAAc) hydrogel formulation and determined its ability to function as a treatment
      option for condylar osteochondral (OC) defects in a New Zealand white rabbit
      (NZWR) model for 12 weeks and 24 weeks. In addition to hydrogel OC implants,
      tensile bar-shaped hydrogels were also implanted subcutaneously to evaluate
      changes in mechanical properties as a function of in vivo duration. There were no
      statistically significant differences (p > 0.05) in the water content measured in
      the OC hydrogel implant that was harvested after 12 weeks and 24 weeks, and non
      implanted controls. There were no statistically significant differences (p >
      0.05) in the break stress, strain at break or modulus of the tensile bars either
      between groups. Histological analysis of the OC defect, synovial capsule and
      fibrous tissue around the tensile bars determined hydrogel biocompatibility.
      Twelve-week hydrogels were found to be in situ flush with the articular
      cartilage; meniscal tissue demonstrated an intact surface. Twenty-four week
      hydrogels protruded from the defect site due to lack of integration with
      subchondral tissue, causing fibrillation to the meniscal surface. Condylar micro
      CT scans ruled out osteolysis and bone cysts of the subchondral bone, and no PVA
      PAAc hydrogel contents were found in the synovial fluid. The PVA-PAAc hydrogel
      was determined to be fully biocompatible, maintained its properties over time,
      and performed well at the 12 week time point. Physical fixation of the PVA-PAAc
      hydrogel to the subchondral bone is required to ensure long-term performance of
      hydrogel plugs for OC defect repair.

PMID- 25050613
TI  - Synthesis and characterization of macromolecular rhodamine tethers and their
      interactions with P-glycoprotein.
AB  - Rhodamine dyes are well-known P-glycoprotein (P-gp) substrates that have played
      an important role in the detection of inhibitors and other substrates of P-gp, as
      well as in the understanding of P-gp function. Macromolecular conjugates of
      rhodamines could prove useful as tethers for further probing of P-gp structure
      and function. Two macromolecular derivatives of rhodamine, methoxypolyethylene
      glycol-rhodamine6G and methoxypolyethylene glycol-rhodamine123, were synthesized
      through the 2'-position of rhodamine6G and rhodamine123, thoroughly
      characterized, and then evaluated by inhibition with verapamil for their ability
      to interact with P-gp and to act as efflux substrates. To put the results into
      context, the P-gp interactions of the new conjugates were compared to the
      commercially available methoxypolyethylene glycol-rhodamineB. FACS analysis
      confirmed that macromolecular tethers of rhodamine6G, rhodamine123, and
      rhodamineB were accumulated in P-gp expressing cells 5.2 +/- 0.3%, 26.2 +/- 4%,
      and 64.2 +/- 6%, respectively, compared to a sensitive cell line that does not
      overexpress P-gp. Along with confocal imaging, the efflux analysis confirmed that
      the macromolecular rhodamine tethers remain P-gp substrates. These results open
      potential avenues for new ways to probe the function of P-gp both in vitro and in
      vivo. 

PMID- 25050614
TI  - Camelina sativa defatted seed meal contains both alkyl sulfinyl glucosinolates
      and quercetin that synergize bioactivity.
AB  - Camelina sativa L. Crantz is under development as a novel oilseed crop, yet
      bioefficacy of camelina phytochemicals is unknown. Defatted camelina seed meal
      contains two major aliphatic glucosinolates (GSLs), glucoarabin (9
      (methylsulfinyl)nonylglucosinolate; GSL 9) and glucocamelinin (10
      (methylsulfinyl)decylglucosinolate; GSL 10), with traces of a third,
      11(methylsulfinyl)undecylglucosinolate and several flavonoids, mostly quercetin
      glycosides. In Hepa1c1c7 cells, hydrolyzed GSLs (hGSLs) 9 and 10 upregulated the
      phase II detoxification enzyme quinone reductase (NQO1), with no effect on
      cytochrome P450 (CYP) 1A1 activity. Isobologram graphs revealed synergy of NQO1
      induction for a combination of hGSL 9 and quercetin. These findings suggest that
      defatted camelina seed meal should be evaluated for anticancer activity, similar
      to broccoli and other Brassicaceae family members. Interestingly, synergy of NQO1
      induction was also seen for physiologically relevant doses of sulforaphane (SF)
      and quercetin, two key bioactives present in broccoli. This suggests that SF
      within broccoli may be more potent than purified SF. 

PMID- 25050615
TI  - Molecular epidemiology of tuberculosis in Cambodian children.
AB  - SUMMARY We analysed Mycobacterium tuberculosis strains from children,
      hospitalized from January 2004 to July 2008 in the largest paediatric hospital
      complex in Cambodia. Specimens were tested for drug susceptibility and genotypes.
      From the 260 children, 161 strains were available. The East African-Indian
      genotype family was the most common (59.0%), increasing in frequency with
      distance from the Phnom Penh area, while the frequency of the Beijing genotype
      family strains decreased. The drug resistance pattern showed a similar
      geographical gradient: lowest in the northwest (4.6%), intermediate in the
      central (17.1%), and highest in the southeastern (30.8%) parts of the country.
      Three children (1.9%) had multidrug-resistant tuberculosis. The Beijing genotype
      and streptomycin resistance were significantly associated (P < 0.001). As
      tuberculosis in children reflects recent transmission patterns in the community,
      multidrug resistance levels inform about the current quality of the tuberculosis
      programme.

PMID- 25050616
TI  - Mechanisms of side branching and tip splitting in a model of branching
      morphogenesis.
AB  - Recent experimental work in lung morphogenesis has described an elegant pattern
      of branching phenomena. Two primary forms of branching have been identified: side
      branching and tip splitting. In our previous study of lung branching
      morphogenesis, we used a 4 variable partial differential equation (PDE), due to
      Meinhardt, as our mathematical model to describe the reaction and diffusion of
      morphogens creating those branched patterns. By altering key parameters in the
      model, we were able to reproduce all the branching styles and the switch between
      branching modes. Here, we attempt to explain the branching phenomena described
      above, as growing out of two fundamental instabilities, one in the longitudinal
      (growth) direction and the other in the transverse direction. We begin by
      decoupling the original branching process into two semi-independent sub
      processes, 1) a classic activator/inhibitor system along the growing stalk, and
      2) the spatial growth of the stalk. We then reduced the full branching model into
      an activator/inhibitor model that embeds growth of the stalk as a controllable
      parameter, to explore the mechanisms that determine different branching patterns.
      We found that, in this model, 1) side branching results from a pattern-formation
      instability of the activator/inhibitor subsystem in the longitudinal direction.
      This instability is far from equilibrium, requiring a large inhomogeneity in the
      initial conditions. It successively creates periodic activator peaks along the
      growing stalk, each of which later on migrates out and forms a side branch; 2)
      tip splitting is due to a Turing-style instability along the transversal
      direction, that creates the spatial splitting of the activator peak into 2
      simultaneously-formed peaks at the growing tip, the occurrence of which requires
      the widening of the growing stalk. Tip splitting is abolished when transversal
      stalk widening is prevented; 3) when both instabilities are satisfied, tip
      bifurcation occurs together with side branching. 

PMID- 25050617
TI  - Roles of the kinase TAK1 in CD40-mediated effects on vascular oxidative stress
      and neointima formation after vascular injury.
AB  - Although TAK1 has been implicated in inflammation and oxidative stress, its roles
      in vascular smooth muscle cells (VSMCs) and in response to vascular injury have
      not been investigated. The present study aimed to investigate the role of TAK1 in
      modulating oxidative stress in VSMCs and its involvement in neointima formation
      after vascular injury. Double immunostaining reveals that vascular injury induces
      a robust phosphorylation of TAK1 (Thr187) in the medial VSMCs of injured arteries
      in wildtype mice, but this effect is blocked in CD40-deficient mice. Upregulation
      of TAK1 in VSMCs is functionally important, as it is critically involved in pro
      oxidative and pro-inflammatory effects on VSMCs and eventual neointima formation.
      In vivo, pharmacological inhibition of TAK1 with 5Z-7-oxozeaenol blocked the
      injury-induced phosphorylation of both TAK1 (Thr187) and NF-kB/p65 (Ser536),
      associated with marked inhibition of superoxide production, 3-nitrotyrosine, and
      MCP-1 in the injured arteries. Cell culture experiments demonstrated that either
      siRNA knockdown or 5Z-7-oxozeaenol inhibition of TAK1 significantly attenuated
      NADPH oxidase activation and superoxide production induced by CD40L/CD40
      stimulation. Co-immunoprecipitation experiments indicate that blockade of TAK1
      disrupted the CD40L-induced complex formation of p22phox with p47phox, p67phox,
      or Nox4. Blockade of TAK1 also inhibited CD40L-induced NF-kB activation by
      modulating IKKalpha/beta and NF-kB p65 phosphorylation and this was related to
      reduced expression of proinflammatory genes (IL-6, MCP-1 and ICAM-1) in VSMCs.
      Lastly, treatment with 5Z-7-oxozeaenol attenuated neointimal formation in wire
      injured femoral arteries. Our findings demonstrate previously uncharacterized
      roles of TAK1 in vascular oxidative stress and the contribution to neointima
      formation after vascular injury. 

PMID- 25050618
TI  - Prevalence of anxiety and depressive symptoms and related risk factors among
      physicians in China: a cross-sectional study.
AB  - BACKGROUND: Physicians' poor mental health not only hinders their professional
      performance and affects the quality of healthcare provided but also adversely
      affects patients' health outcomes. Few studies in China have evaluated the mental
      health of physicians. The purposes of this study are to quantify Chinese
      physicians' anxiety and depressive symptoms as well as evaluate associated risk
      factors. METHODS: In our study, 2641 physicians working in public hospitals in
      Shenzhen in southern China were recruited and interviewed by using a structured
      questionnaire along with validated scales testing anxiety and depressive
      symptoms. Multivariable logistic regression models were used to identify risk
      factors for anxiety and depressive symptoms. RESULTS: An estimated 25.67% of
      physicians had anxiety symptoms, 28.13% had depressive symptoms, and 19.01% had
      both anxiety and depressive symptoms. More than 10% of the participants often
      experienced workplace violence and 63.17% sometimes encountered it. Among our
      study population, anxiety and depressive symptoms were associated with poor self
      reported physical health, frequent workplace violence, lengthy working hours
      (more than 60 hours a week), frequent night shifts (twice or more per week), and
      lack of regular physical exercise. CONCLUSIONS: Our study demonstrates that
      anxiety and depressive symptoms are common among physicians in China, and the
      doctor-patient relationship issue is particularly stressful. Interventions
      implemented to minimize workload, improve doctor-patient relationships, and
      assist physicians in developing healthier lifestyles are essential to combat
      anxiety and depressive symptoms among physicians, which may improve their
      professional performance.

PMID- 25050619
TI  - Does diagnosing fatty liver and chronic kidney disease do more good than harm?

PMID- 25050620
TI  - Survivin as a potential mediator to support autoreactive cell survival in
      myasthenia gravis: a human and animal model study.
AB  - The mechanisms that underlie the development and maintenance of autoimmunity in
      myasthenia gravis are poorly understood. In this investigation, we evaluate the
      role of survivin, a member of the inhibitor of apoptosis protein family, in
      humans and in two animal models. We identified survivin expression in cells with
      B lymphocyte and plasma cells markers, and in the thymuses of patients with
      myasthenia gravis. A portion of survivin-expressing cells specifically bound a
      peptide derived from the alpha subunit of acetylcholine receptor indicating that
      they recognize the peptide. Thymuses of patients with myasthenia gravis had large
      numbers of survivin-positive cells with fewer cells in the thymuses of
      corticosteroid-treated patients. Application of a survivin vaccination strategy
      in mouse and rat models of myasthenia gravis demonstrated improved motor
      assessment, a reduction in acetylcholine receptor specific autoantibodies, and a
      retention of acetylcholine receptor at the neuromuscular junction, associated
      with marked reduction of survivin-expressing circulating CD20+ cells. These data
      strongly suggest that survivin expression in cells with lymphocyte and plasma
      cell markers occurs in patients with myasthenia gravis and in two animal models
      of myasthenia gravis. Survivin expression may be part of a mechanism that
      inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other
      autoimmune disorders. 

PMID- 25050621
TI  - MicroRNAs MiR-218, MiR-125b, and Let-7g predict prognosis in patients with oral
      cavity squamous cell carcinoma.
AB  - MicroRNAs (miRNAs) have a major impact on regulatory networks in human
      carcinogenesis. In this study, we sought to investigate the prognostic
      significance of miRNAs in patients with oral cavity squamous cell carcinoma
      (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and
      paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and
      TaqMan MicroRNA assays. The prognostic significance of the miRNA signature
      identified in the discovery phase was validated by qRT-PCR in a replication set
      consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified
      a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53)
      that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and
      let-7g) and their downstream response genes had a concordant prognostic
      significance on disease-free survival and disease-specific survival rates. In
      addition, patients with a reduced expression of miR-218, miR-125b, and let-7g
      have a higher risk of poor outcomes in presence of specific risk factors (p-stage
      III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have
      prognostic significance in OSCC patients and may improve prognostic
      stratification over traditional risk factors. 

PMID- 25050623
TI  - Thoracic rat spinal cord contusion injury induces remote spinal gliogenesis but
      not neurogenesis or gliogenesis in the brain.
AB  - After spinal cord injury, transected axons fail to regenerate, yet significant,
      spontaneous functional improvement can be observed over time. Distinct central
      nervous system regions retain the capacity to generate new neurons and glia from
      an endogenous pool of progenitor cells and to compensate neural cell loss
      following certain lesions. The aim of the present study was to investigate
      whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain
      (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor
      cortex, MC) or cervical spinal cord might represent a structural correlate for
      spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer
      344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal
      cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From
      4 to 14 days post-injury, both groups received injections of bromodeoxyuridine
      (BrdU) to label dividing cells. Over the course of six weeks post-injury,
      spontaneous recovery of locomotor function occurred. Survival of newly generated
      cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined
      by identification and quantification of doublecortin immunoreactive neuroblasts
      or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not
      present in non-neurogenic regions (MC, CC, and cervical spinal cord) and
      unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of
      neuronal replacement in the brain and spinal cord after spinal cord injury
      precludes any relevance for spontaneous recovery of locomotor function.
      Gliogenesis was increased in the cervical spinal cord remote from the injury
      site, however, is unlikely to contribute to functional improvement. 

PMID- 25050622
TI  - Insights into the molecular evolution of HslU ATPase through biochemical and
      mutational analyses.
AB  - The ATP-dependent HslVU complexes are found in all three biological kingdoms. A
      single HslV protease exists in each species of prokaryotes, archaea, and
      eukaryotes, but two HslUs (HslU1 and HslU2) are present in the mitochondria of
      eukaryotes. Previously, a tyrosine residue at the C-terminal tail of HslU2 has
      been identified as a key determinant of HslV activation in Trypanosoma brucei and
      a phenylalanine at the equivalent position to E. coli HslU is found in T. brucei
      HslU1. Unexpectedly, we found that an F441Y mutation in HslU enhanced the
      peptidase and caseinolytic activity of HslV in E. coli but it showed partially
      reduced ATPase and SulA degradation activity. Previously, only the C-terminal
      tail of HslU has been the focus of HslV activation studies. However, the Pro315
      residue interacting with Phe441 in free HslU has also been found to be critical
      for HslV activation. Hence, our current biochemical analyses explore the
      importance of the loop region just before Pro315 for HslVU complex functionality.
      The proline and phenylalanine pair in prokaryotic HslU was replaced with the
      threonine and tyrosine pair from the functional eukaryotic HslU2. Sequence
      comparisons between multiple HslUs from three different biological kingdoms in
      combination with biochemical analysis of E. coli mutants have uncovered important
      new insights into the molecular evolutionary pathway of HslU. 

PMID- 25050624
TI  - Effects of leucine supplementation and serum withdrawal on branched-chain amino
      acid pathway gene and protein expression in mouse adipocytes.
AB  - The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine,
      are traditionally associated with skeletal muscle growth and maintenance, energy
      production, and generation of neurotransmitter and gluconeogenic precursors.
      Recent evidence from human and animal model studies has established an additional
      link between BCAA levels and obesity. However, details of the mechanism of
      regulation of BCAA metabolism during adipogenesis are largely unknown. We
      interrogated whether the expression of genes and proteins involved in BCAA
      metabolism are sensitive to the adipocyte differentiation process, and responsive
      to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes
      were differentiated to adipocytes under control conditions and under conditions
      of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated
      at days 0, 4 and 10 of differentiation to represent pre-differentiation, early
      differentiation and late differentiation stages. Expression of 16 BCAA metabolism
      genes was quantified by quantitative real-time PCR. Expression of the protein
      levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain
      alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under
      control conditions, all genes displayed induction of gene expression during early
      adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an
      induction of Bcat2 and Bckdha genes during early and late differentiation.
      Western blot analysis demonstrated condition-specific concordance between gene
      and protein expression. Serum withdrawal resulted in undetectable Bcat2 and
      Bckdha protein levels at all timepoints. These results demonstrate that the
      expression of genes related to BCAA metabolism are regulated during adipocyte
      differentiation and influenced by nutrient levels. These results provide
      additional insights on how BCAA metabolism is associated with adipose tissue
      function and extends our understanding of the transcriptomic response of this
      pathway to variations in nutrient availability. 

PMID- 25050625
TI  - Functional effect of polymorphisms in the promoter of TNFAIP3 (A20) in acute
      pancreatitis in the Han Chinese population.
AB  - BACKGROUND: The zinc finger protein A20 is an important negative regulator of
      inflammation; polymorphisms in the corresponding gene, TNFAIP3, have been
      reported to be associated with several inflammation diseases. However, only a few
      studies have focused on the relationship between TNFAIP3 polymorphisms and acute
      pancreatitis (AP). METHODS: We enrolled 201 healthy controls and 190 acute
      pancreatitis patients (including 47 systemic inflammatory response syndrome
      patients) for this study and used DNA sequencing to investigate polymorphisms in
      the TNFAIP3 promoter. The functional effects of these variants on transcriptional
      activity, A20 expression, NF-kappaB activity, and TNF-alpha and IL-1beta levels,
      after in vitro lipopolysaccharide stimulation, were assessed. RESULTS: Two SNPs
      (rs59693083 and rs5029924) in the TNFAIP3 promoter were selected based on
      bioinformatic analysis. Neither of these SNPs was associated with susceptibility
      to AP; however, acute pancreatitis patients who possessed the T allele of
      rs5029924 were more likely to experience systemic inflammatory response syndrome.
      Moreover, rs5029924 was found to affect TNFAIP3 promoter activity. After
      lipopolysaccharide stimulation, the expression of A20 protein significantly
      decreased, while the activity of NF-kappaB and the production of TNF-alpha and IL
      1beta significantly increased in whole blood leukocytes from subjects with the T
      allele. CONCLUSION: The rs5029924 polymorphism in the TNFAIP3 promoter may alter
      the risk of systemic inflammatory response syndrome in acute pancreatitis
      patients by influencing the expression of A20 protein.

PMID- 25050627
TI  - Rosiglitazone suppresses angiogenesis in multiple myeloma via downregulation of
      hypoxia-inducible factor-1alpha and insulin-like growth factor-1 mRNA expression.
AB  - Rosiglitazone (RGZ) is a thiazolidinedione ligand of peroxisome proliferator
      activated receptor-gamma. Our previous studies have confirmed that RGZ possesses
      antitumoral properties. Bone marrow angiogenesis exhibits an important role in
      multiple myeloma (MM), and angiogenesis often correlates with the prognosis and
      disease burden of MM. However, to the best of our knowledge, inhibition of
      angiopoiesis by RGZ in MM has not yet been reported. The present study aimed to
      investigate whether RGZ prevents angiogenesis and the possible underlying
      mechanism of this effect in MM. RPMI-8226 cells, primary myeloma cells from
      patients with MM or mononuclear cells from healthy patients were treated with
      different concentrations of RGZ, and various biological responses were detected
      using MTT, reverse transcription-polymerase chain reaction and western blot
      assays. The expression levels of hypoxia-inducible transcription factor-1alpha
      (HIF1alpha) and insulin-like growth factor-1 (IGF1) were significantly increased
      in the RPMI-8226 cells and the primary myeloma cells from the patients with MM
      compared with those in the mononuclear cells from the healthy patients. The
      results also showed that RGZ was able to inhibit proliferation and reduce
      viability of RPMI-8226 cells in a concentration-and time-dependent manner. RGZ
      was able to concentration-dependently inhibit the expression of HIF1alpha and
      IGF1 mRNA in RPMI-8226 and primary myeloma cells from patients with MM. RGZ also
      inhibited the expression of pAKT and downregulated the expression levels of
      phosphorylated extracellular signal-regulated kinase (ERK) in RPMI-8226 cells.
      The results suggested that RGZ inhibits the angiopoiesis of tumors by interfering
      with the phosphatidylinositol 3-kinase/AKT and ERK signaling pathways.

PMID- 25050628
TI  - Proteolytic stability of amphipathic peptide hydrogels composed of self-assembled
      pleated beta-sheet or coassembled rippled beta-sheet fibrils.
AB  - Hydrogel networks composed of rippled beta-sheet fibrils of coassembled D- and L
      Ac-(FKFE)2-NH2 amphipathic peptides exhibit proteolytic stability and increased
      rheological strength compared to networks of self-assembled L-Ac-(FKFE)2-NH2
      pleated beta-sheet fibrils. Modifying the ratios of l and d peptides in the
      coassembled rippled beta-sheet fibrils alters the degradation profiles of these
      hydrogel networks.

PMID- 25050629
TI  - Enantiomerically pure trinuclear helicates via diastereoselective self-assembly
      and characterization of their redox chemistry.
AB  - A tris(bipyridine) ligand 1 with two BINOL (BINOL = 2,2'-dihydroxy-1,1'
      binaphthyl) groups has been prepared in two enantiomerically pure forms. This
      ligand undergoes completely diastereoselective self-assembly into D2-symmeteric
      double-stranded trinuclear helicates upon coordination to copper(I) and silver(I)
      ions and to D3-symmetric triple-stranded trinuclear helicates upon coordination
      to copper(II), zinc(II), and iron(II) ions as demonstrated by mass spectrometry,
      NMR and CD spectroscopy in combination with quantum chemical calculations and X
      ray diffraction analysis. According to the calculations, the single diastereomers
      that are formed during the self-assembly process are strongly preferred compared
      to the next stable diastereomers. Due to this strong preference, the self
      assembly of the helicates from racemic 1 proceeds in a completely narcissistic
      self-sorting manner with an extraordinary high degree of self-sorting that proves
      the power and reliability of this approach to achieve high-fidelity
      diastereoselective self-assembly via chiral self-sorting to get access to
      stereochemically well-defined nanoscaled objects. Furthermore, mass spectrometric
      methods including electron capture dissociation MS(n) experiments could be used
      to elucidate the redox behavior of the copper helicates. 

PMID- 25050630
TI  - Circularly polarized luminescence from individual microstructures of conjugated
      polymer aggregates with solvent-induced chirality.
AB  - We report a microscopic study of circularly polarized luminescence (CPL) from R
      and S isomers of aggregates of the conjugated polymer F8BT, a copolymer
      containing fluorene and thiophene monomer units. Chirality in the aggregates is
      induced by addition of either (R)- or (S)-limonene during aggregation in
      solution. Solid-state samples are prepared either by drop-casting or spin-coating
      of the aggregate solution. CPL dissymmetry parameter g measured for individual
      aggregate microstructures shows a broad distribution of values ranging from
      positive to negative even for the same isomer. The difference in the centers of
      the g distribution between the R and S isomers reflects the intrinsic CPL from
      the chiral aggregates, and is found to depend on the size of the aggregate
      structures. On the other hand, the large widths of the distributions are ascribed
      to an optical effect arising from phase retardation along the optical path of the
      CPL inside the sample.

PMID- 25050632
TI  - Indications, techniques and outcomes for pelvic exenteration in gynecological
      malignancy.
AB  - PURPOSE OF REVIEW: To review recently published literature presenting an overview
      of the current insights and (clinical and technical) developments on pelvic
      exenterative surgery for gynecological malignancies. RECENT FINDINGS: Lateral
      recurrences, positive pelvic node status, age and high body mass index should be
      abandoned as contraindications for pelvic exenteration. F-fluorodeoxyglucose
      positron emission tomography-computed tomography is a valuable imaging tool,
      especially for the detection of enlarged lymph nodes and for distinguishing
      fibrosis from recurrence. Combined omental plus vertical rectus abdominis
      myocutaenous flaps give significant reduction in complications, whereas fascia
      sparing (myo)cutaneous flaps seem promising in decreasing donor-site
      complications. SUMMARY: Pelvic exenteration is indicated when curative
      alternatives are inferior or exhausted for advanced primary or locally
      gynecological recurrent cancer confined to the pelvis. Palliative pelvic
      exenteration should only be considered when disease-related morbidity is
      uncontrollable with other therapeutic modalities. Modifications in different
      surgical steps are still evolving to decrease the pelvic exenteration associated
      high morbidity. A complete resection and lymph node invasion free status are
      directly related to a better prognosis.

PMID- 25050631
TI  - Differentially expressed genes and interacting pathways in bladder cancer
      revealed by bioinformatic analysis.
AB  - The goal of this study was to identify cancer-associated differentially expressed
      genes (DEGs), analyze their biological functions and investigate the mechanism(s)
      of cancer occurrence and development, which may provide a theoretical foundation
      for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling
      dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes
      165 BCa and 68 control samples. T-tests were used to identify DEGs. To further
      study the biological functions of the identified DEGs, we performed a Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we
      built a network of potentially interacting pathways to study the synergistic
      relationships among DEGs. A total of 12,105 genes were identified as DEGs, of
      which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs
      encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT)
      proteins, nuclear factor kappa-light-chain-enhancer of activated B cells (NF
      kappaB) and interleukin (IL)-10 were revealed to participate in the significantly
      enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis
      revealed 7 significantly upregulated and 47 significantly downregulated pathways
      enriched among the DEGs. We found a crosstalk interaction among a total of 44
      pathways in the network of BCa-affected pathways. In conclusion, our results show
      that BCa involves dysfunctions in multiple systems. Our study is expected to pave
      ways for immune and inflammatory research and provide molecular insights for
      cancer therapy.

PMID- 25050633
TI  - Sphingosine-1-phosphate inhibits the adipogenic differentiation of 3T3-L1
      preadipocytes.
AB  - Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits
      signals through G-protein-coupled receptors to control diverse biological
      processes. The novel biological activity of S1P in the adipogenesis of 3T3-L1
      preadipocytes was identified in the present study. S1P significantly decreased
      lipid accumulation in maturing preadipocytes in a dose-dependent manner. In order
      to understand the anti-adipogenic effects of S1P, preadipocytes were treated with
      S1P, and the change in the expression of several adipogenic transcription factors
      and enzymes was investigated using quantitative RT-PCR. S1P downregulated the
      transcriptional levels of the peroxisome proliferator-activated receptor gamma,
      CCAAT/enhancer binding proteins and adiponectin, which are markers of adipogenic
      differentiation. The effects of S1P on the levels of mitogen-activated protein
      kinase (MAPK) signals in preadipocytes were also investigated. The activation of
      JNK and p38 were downregulated by S1P treatment in human preadipocytes. In
      conclusion, the results of this study suggest that S1P alters fat mass by
      directly affecting adipogenesis. This is mediated by the downregulation of
      adipogenic transcription factors and by inactivation of the JNK and p38 MAPK
      pathways. Thus, selective targeting of the S1P receptors and sphingosine kinases
      may have clinical applications for the treatment of obesity.

PMID- 25050634
TI  - Inverse transfer method using polymers with various functional groups for
      controllable graphene doping.
AB  - The polymer-supported transfer of chemical vapor deposition (CVD)-grown graphene
      provides large-area and high-quality graphene on a target substrate; however, the
      polymer and organic solvent residues left by the transfer process hinder the
      application of CVD-grown graphene in electronic and photonic devices. Here, we
      describe an inverse transfer method (ITM) that permits the simultaneous transfer
      and doping of graphene without generating undesirable residues by using polymers
      with different functional groups. Unlike conventional wet transfer methods, the
      polymer supporting layer used in the ITM serves as a graphene doping layer placed
      at the interface between the graphene and the substrate. Polymers bearing
      functional groups can induce n-doping or p-doping into the graphene depending on
      the electron-donating or -withdrawing characteristics of functional groups.
      Theoretical models of dipole layer-induced graphene doping offered insights into
      the experimentally measured change in the work function and the Dirac point of
      the graphene. Finally, the electrical properties of pentacene field effect
      transistors prepared using graphene electrodes could be enhanced by employing the
      ITM to introduce a polymer layer that tuned the work function of graphene. The
      versatility of polymer functional groups suggests that the method developed here
      will provide valuable routes to the development of applications of CVD-grown
      graphene in organic electronic devices. 

PMID- 25050635
TI  - Facile, one-pot synthesis, and antibacterial activity of mesoporous silica
      nanoparticles decorated with well-dispersed silver nanoparticles.
AB  - In this study, we exploit a facile, one-pot method to prepare MCM-41 type
      mesoporous silica nanoparticles decorated with silver nanoparticles (Ag-MSNs).
      Silver nanoparticles with diameter of 2-10 nm are highly dispersed in the
      framework of mesoporous silica nanoparticles. These Ag-MSNs possess an enhanced
      antibacterial effect against both Gram-positive and Gram-negative bacteria by
      preventing the aggregation of silver nanoparticles and continuously releasing
      silver ions for one month. The cytotoxicity assay indicates that the effective
      antibacterial concentration of Ag-MSNs shows little effect on human cells. This
      report describes an efficient and economical route to synthesize mesoporous
      silica nanoparticles with uniform silver nanoparticles, and these nanoparticles
      show promising applications as antibiotics. 

PMID- 25050636
TI  - Synthesis, characterization, and linkage isomerism in mononuclear ruthenium
      complexes containing the new pyrazolate-based ligand Hpbl.
AB  - A new tetradentate dinucleating ligand [1,1'-(4-methyl-1H-pyrazole-3,5-diyl)bis(1
      (pyridin-2-yl)ethanol)] (Hpbl) containing an O/N mixed donor set of atoms has
      been synthesized and characterized by analytical and spectroscopic techniques.
      The Ru-Cl and Ru-aqua complexes containing this ligand of general formula
      [Ru(II)X(Hpbl)(trpy)](y+) (trpy = 2,2':6',2"-terpyridine; X = Cl, y = 1; X = H2O,
      y = 2) have been prepared and thoroughly characterized by spectroscopic and
      electrochemical techniques. The Ru-aqua complex 2 undergoes N -> O linkage
      isomerization as observed electrochemically, and the related thermodynamic and
      kinetic parameters are extracted from cyclic voltammetry experiments together
      with DIGISIM, a CV simulation package. Under basic conditions an additional
      isomer is observed where the pyrazolyl group in the Hpbl ligand is replaced by
      the geminal pyridyl group. Further structural and electronic characterization of
      all the isomers has been carried out by means of DFT calculations. 

PMID- 25050640
TI  - Synthesis of 3-(hetero)aryl tetrahydropyrazolo[3,4-c]pyridines by Suzuki-Miyaura
      cross-coupling methodology.
AB  - A new synthetic route to 3-(heteroaryl) tetrahydropyrazolo[3,4-c]pyridines has
      been developed that uses the Suzuki-Miyaura cross-coupling of a triflate 6 with
      (hetero)aryl boronic acids or esters. Using Pd(OAc)2 and XPhos or an XPhos
      precatalyst, a diverse range of substituents at the C3 position of the
      tetrahydropyrazolo[3,4-c]pyridine skeleton were prepared. The use of
      pivaloyloxymethyl and benzyl protection also offers the potential to
      differentially functionalize the pyrazole and tetrahydropyridine nitrogens. 

PMID- 25050642
TI  - "She never smoked a day in her life.".

PMID- 25050641
TI  - A comprehensive search for microRNAs with expression profiles modulated by
      oncogenic KRAS: potential involvement of miR-31 in lung carcinogenesis.
AB  - Small non-protein coding RNAs that regulate messenger RNA levels, namely
      microRNAs (miRNAs), have been implicated in the pathogenesis of various diseases.
      The purpose of the present study was to identify essential miRNAs involved in
      lung carcinogenesis. Previous studies demonstrated that an investigation into the
      downstream targets of oncogenic KRAS could be used as a strategy to elucidate the
      molecular mechanisms involved in lung cancer; therefore, we examined the
      expression profiles of mRNAs modulated by oncogenic KRAS in the present study. We
      focused on miR-31 from the miRNAs that were differentially expressed, and
      evaluated its potential role in the development of lung cancer. miR-31 was
      upregulated not only by oncogenic KRAS, but also by oncogenic EGFR. The
      expression of miR-31 was markedly attenuated in some lung cancer cell lines by
      deleting its host gene locus. The restoration of miR-31 in lung cancer cell lines
      that lost its expression attenuated their growth activities. The knockdown of miR
      31 expression in lung cancer cell lines retaining its expression enhanced
      anchorage-independent growth activity. These results suggest that miR-31 may be a
      suppressor that regulates an essential oncogenic pathway, the loss of which may
      promote lung carcinogenesis. 

PMID- 25050643
TI  - Theoretical study of the structural stability of molecular chain sheet models of
      cellulose crystal allomorphs.
AB  - The structural stabilities of the molecular chain sheets constituting the crystal
      structures of the cellulose allomorphs Ialpha, Ibeta, II, and IIII were
      investigated by density functional theory (DFT) optimization of the isolated
      chain sheet models with finite dimensions. The DFT-optimized chain sheet models
      of the two native cellulose crystals developed a right-handed twist with a
      similar amount of twisting. The DFT-optimized cellulose II (010) and (020) models
      twisted in opposite directions with right- and left-handed chirality,
      respectively. The cellulose IIII (1-10) model retained the initial flat structure
      after the DFT-optimization. The structural features of the DFT-optimized chain
      sheet models were reflected in the structures of the parent crystal models
      observed in solvated molecular dynamics (MD) simulations. The minor conformations
      of the hydroxymethyl groups proposed in the real crystal structures were detected
      in the MD crystal models and the DFT-optimized (010) model of cellulose II. The
      crystal chain packing and crystal conversions are interpreted in terms of
      principal chain sheet stacking. 

PMID- 25050644
TI  - In vitro performance of spacers for aerosol delivery during adult mechanical
      ventilation.
AB  - BACKGROUND: During mechanical ventilation, different aerosol generators are
      employed with various interfaces. The objective of this study was to evaluate the
      performance of a range of spacers, including a new device called Combihaler(r)
      designed for connection with both nebulizers and pressurized Metered-Dose
      Inhalers (pMDIs). METHODS: To assess the spacers, we used a ventilator and the
      Dual Adult Training and Test Lung (model 5600i, Michigan Instruments).
      Ventilation parameters were measured with and without spacers in volume
      controlled and pressure-controlled mode. A filter was placed at the end of the
      endotracheal tube to measure aerosol delivery. Amikacin (1 g/8 mL) and salbutamol
      (5 mg/5 mL) were nebulized with an Aeroneb Solo(r) connected to its T-adapter or
      the Combihaler(r) spacer. Salbutamol (100 MUg/actuation with 10 actuations) and
      beclomethasone (250 MUg/actuation with 10 actuations) were delivered with a pMDI
      connected to a Minispacer(r), an ACE(r) spacer, or a Combihaler(r) spacer. Drug
      delivery measurements were performed in volume-controlled mode in dry and
      humidified conditions. Drug deposits on the filter were assayed. RESULTS: The use
      of spacers and the T-adapter did not change the ventilation parameters (p>0.9).
      Aerosol delivery of salbutamol and Amikacin by nebulization increased up to three
      fold with the Combihaler(r) compared with the T-adapter in humidified and
      nonhumidified conditions (p<0.05). Aerosol delivery of salbutamol and
      beclometasone by pMDI increased up to three-fold with the Combihaler(r) and the
      ACE(r) spacer compared with the Minispacer(r) in humidified and nonhumidified
      conditions (p<0.05). Aerosol delivery by pMDIs and vibrating mesh nebulizers
      using either a T-adapter or spacers was reduced by up to 62.5% in a humidified
      circuit compared with a nonhumidified circuit. CONCLUSION: Aerosol delivery via
      pMDIs and vibrating mesh nebulizers is greater with large spacers (Combihaler(r)
      and ACE(r)) than with smaller spacers (Minispacer(r)) or a T-adapter, in both
      humidified and nonhumidified conditions. In humidified conditions, the aerosol
      delivery decreased with all spacers.

PMID- 25050645
TI  - Transfer, transformation, and impacts of ceria nanomaterials in aquatic mesocosms
      simulating a pond ecosystem.
AB  - Mesocosms are an invaluable tool for addressing the complex issue of exposure
      during nanoecotoxicological testing. This experimental strategy was used to take
      into account parameters as the interactions between the NPs and naturally
      occurring (in)organic colloids (heteroaggregation), or the flux between
      compartments of the ecosystems (aqueous phase, sediments, biota) when assessing
      the impacts of CeO2 NPs in aquatic ecosystems. In this study, we determine the
      transfer, redox transformation, and impacts of 1 mg L(-1) of bare and citrate
      coated CeO2-NPs toward an ecologically relevant organism (snail, Planorbarius
      corneus) exposed 4 weeks in a complex experimental system mimicking a pond
      ecosystem. Over time, CeO2-NPs tend to homo- and heteroaggregate and to
      accumulate on the surficial sediment. The kinetic of settling down was coating
      dependent and related to the coating degradation. After 4 weeks, Ce was observed
      in the digestive gland of benthic organisms and associated with 65-80% of Ce(IV)
      reduction into Ce(III) for both bare and coated CeO2 NPs. A transitory oxidative
      stress was observed for bare CeO2-NPs. Coated-NPs exposed snails did not undergo
      any lipid peroxidation nor change in the antioxidant contents, while Ce content
      and reduction in the digestive gland were identical to bare CeO2-NPs. We
      hypothesized that the presence of citrate coating enhanced the defense capacity
      of the cells toward the oxidative stress induced by the CeO2 core. 

PMID- 25050647
TI  - Association of left atrial reservoir function with left atrial structural
      remodeling related to left ventricular dysfunction in asymptomatic patients with
      hypertension: evaluation by two-dimensional speckle-tracking echocardiography.
AB  - Left atrial (LA) structural and functional abnormalities are vital steps on the
      pathway toward heart failure with preserved ejection fraction in asymptomatic
      patients. The purpose of this study was to assess the relationship of LA
      function, particularly reservoir function, with LA structural remodeling related
      to the left ventricular (LV) dysfunction in asymptomatic patients with
      hypertension (HT) using conventional, tissue Doppler, and 2-D speckle-tracking
      echocardiography. Fifty age-matched healthy individuals and 140 patients with HT,
      including 75 with LA volume index (LAVI)<29 ml/m2 (normal LA group) and 65 with
      LAVI>=29 ml/m2 (large LA group), were enrolled. We defined peak early diastolic
      transmitral flow velocity/peak early diastolic mitral annular motion velocity
      (E/e')/peak systolic LA strain (S-LAs) as LA diastolic stiffness. The LV mass
      index, relative LV wall thickness, peak atrial systolic transmitral flow
      velocity, LA total, active, and passive emptying volume indexes, and E/e'/S-LAs
      were greatest, and S-LAs, peak early diastolic LA strain, peak systolic LV
      longitudinal strain and circumferential strain rate, and peak early diastolic LV
      radial strain rate were lower in the large LA group compared with control and/or
      normal LA group. Multivariate linear regression analysis revealed that aging, LA
      remodeling, and LV systolic and diastolic dysfunction are defined as strong
      predictors related to increased LA diastolic stiffness in the large LA group. HT
      alters LA dynamics significantly, with resultant increased LA volume and
      diastolic stiffness related to LV diastolic and systolic dysfunction, even in
      asymptomatic patients. Earlier treatment with renin?angiotensin system inhibitors
      may improve abnormal LA-LV interaction in this patient population.

PMID- 25050648
TI  - Polyampholyte polymers as a versatile zwitterionic biomaterial platform.
AB  - Polyampholyte polymers are a subclass of zwitterionic materials that are composed
      of mixtures of charged monomer subunits. These materials have properties that
      mimic those of the more widely characterized zwitterionic polymers as long as
      their polymer chemistry has been well controlled. In particular, overall neutral
      polyampholyte polymers have been shown to have resistance to nonspecific protein
      adsorption and protein conjugation capability. This has been demonstrated for
      both polymer brush and hydrogel-based platforms. In this review, our recent work
      demonstrating these characteristics will be summarized and placed into the
      broader context of zwitterionic materials. 

PMID- 25050649
TI  - Visual concerns that interfere with daily activities in patients on
      rehabilitation units: a descriptive study.
AB  - The purpose of this study was to estimate the prevalence of patients with visual
      concerns that interfere with their activities of daily living (ADL) performance
      in physical rehabilitation units through occupational therapy assessment. Over
      the two-month study period, 215 adult inpatients from a physical rehabilitation
      hospital were evaluated using the Brief Vision Screen (BVS) through ADL. The BVS
      assessed four areas of visual concerns, namely left visual field, focusing, and
      near- and low-contrast acuity, while patients engaged in ADL. The occupational
      therapists identified 33% of patients who had at least one area of visual
      concern, with the largest proportion diagnosed with stroke (55%), followed by
      pulmonary disease (40%) and joint replacement (35%). When comparing the four
      areas of visual concerns in the BVS between the two major diagnostic groups
      (acquired brain injury, ABI and non-acquired brain injury, non-ABI), a
      significantly higher proportion of patients with ABI were identified as having
      left hemianopsia concerns compared to patients with non-ABI. No significant
      difference was observed in other areas of visual concern between the two groups.
      Findings indicated that visual concerns that interfere with ADL performance among
      older patients in rehabilitation units are common. The high proportion of
      patients with pulmonary disease identified as having visual concerns warranted
      further confirmation and investigation. Preliminary evidence to support the
      psychometric properties of the BVS for identifying visual concerns in patients on
      rehabilitation units was established.

PMID- 25050650
TI  - Alcohol use, working conditions, job benefits, and the legacy of the "Dop" system
      among farm workers in the Western Cape Province, South Africa: hope despite high
      levels of risky drinking.
AB  - This study describes alcohol consumption in five Western Cape Province
      communities. Cross-sectional data from a community household sample (n = 591)
      describe the alcohol use patterns of adult males and females, and farm workers
      vs. others. Data reveal that men were more likely to be current drinkers than
      women, 75.1% vs. 65.8% (p = 0.033); farm laborers were more likely to be current
      drinkers than individuals in other occupations 83.1% vs. 66.8% (p = 0.004).
      Group, binge drinking on weekends was the norm; men were more likely to be binge
      drinkers in the past week than women 59.8% vs. 48.8% (p = 0.086); farm workers
      were more likely to binge than others 75.0% vs. 47.5% (p < 0.001). The legacy of
      "Dop" contributes to current risky drinking behaviors. Farm owners or managers
      were interviewed on 11 farms, they described working conditions on their farms
      and how the legacy of "Dop" is reflected in the current use of alcohol by their
      workers. "Dop" was given to farm workers in the past on six of the 11 farms, but
      was discontinued for different reasons. There is zero tolerance for coming to
      work intoxicated; farm owners encourage responsible use of alcohol and assist
      farm workers in getting help for alcohol problems when necessary. The farm owners
      report some positive initiatives, were ahead of the movement to provide
      meaningful wages, and provide other important amenities. Further research is
      needed to assess whether progressive practices on some farms will reduce harmful
      alcohol use. 

PMID- 25050651
TI  - Prevalence of overweight/obesity and its associated factors among university
      students from 22 countries.
AB  - Obesity among young people increases lifetime cardiovascular risk. This study
      assesses the prevalence of overweight/obesity and its associated factors among a
      random sample of university students from 22 universities in 22 low, middle
      income and emerging economy countries. This cross-sectional survey comprised of a
      self-administered questionnaire and collected anthropometric measurements. The
      study population was 6773 (43.2%) males and 8913 (56.8%) females, aged 16 to 30
      years (mean 20.8 years, SD = 2.6). Body mass index (BMI) was used for weight
      status. Among men, the prevalence of underweight was 10.8%, normal weight 64.4%,
      overweight 18.9% and obesity 5.8%, while among women, the prevalence of
      underweight was 17.6%, normal weight 62.1%, overweight 14.1% and obesity 5.2%.
      Overall, 22% were overweight or obese (24.7% men and 19.3% women). In
      multivariate regression among men, younger age, coming from a higher income
      country, consciously avoiding fat and cholesterol, physically inactivity, current
      tobacco use and childhood physical abuse, and among women older age, coming from
      a higher income country, frequent organized religious activity, avoiding fat and
      cholesterol, posttraumatic stress symptoms and physical childhood abuse were
      associated overweight or obesity. Several gender specific risk factors identified
      can be utilized in health promotion programmes. 

PMID- 25050652
TI  - Trends of non-accidental, cardiovascular, stroke and lung cancer mortality in
      Arkansas are associated with ambient PM2.5 reductions.
AB  - The cardiovascular and stroke mortality rates in Arkansas are among the highest
      in the USA. The annual trends of stroke and cardiovascular mortality are barely
      correlated to smoking cessation; while the prevalence of risk factors such as
      obesity; cholesterol and hypertension increased over the 1979-2007 period. The
      study determined the effect of chronic exposure to PM2.5 on non-accidental;
      cardiovascular; stroke and lung cancer mortality in Arkansas over the 2000-2010
      period using the World Health Organization's log-linear health impact model.
      County chronic exposures to PM2.5 were computed by averaging spatially-resolved
      gridded concentrations using PM2.5 observations. A spatial uniformity was
      observed for PM2.5 mass levels indicating that chronic exposures were comparable
      throughout the state. The reduction of PM2.5 mass levels by 3.0 MUg/m3 between
      2000 and 2010 explained a significant fraction of the declining mortality. The
      effect was more pronounced in southern and eastern rural Arkansas as compared to
      the rest of the state. This study provides evidence that the implementation of
      air pollution regulations has measurable effects on mortality even in regions
      with high prevalence of major risk factors such as obesity and smoking. These
      outcomes are noteworthy as efforts to modify the major risk factors require
      longer realization times. 

PMID- 25050653
TI  - A synthetic thiourea-based tripodal receptor that impairs the function of human
      first trimester cytotrophoblast cells.
AB  - A synthetic tripodal-based thiourea receptor (PNTTU) was used to explore the
      receptor/ligand binding affinity using CTB cells. The human extravillous CTB
      cells (Sw.71) used in this study were derived from first trimester chorionic
      villus tissue. The cell proliferation, migration and angiogenic factors were
      evaluated in PNTTU-treated CTB cells. The PNTTU inhibited the CTBs proliferation
      and migration. The soluble fms-like tyrosine kinase-1 (sFlt-1) secretion was
      increased while vascular endothelial growth factor (VEGF) was decreased in the
      culture media of CTB cells treated with >=1 nM PNTTU. The angiotensin II receptor
      type 2 (AT2) expression was significantly upregulated in >=1 nM PNTTU-treated CTB
      cells in compared to basal; however, the angiotensin II receptor, type 1 (AT1)
      and vascular endothelial growth factor receptor 1 (VEGFR-1) expression was
      downregulated. The anti-proliferative and anti-angiogenic effect of this compound
      on CTB cells are similar to the effect of CTSs. The receptor/ligand affinity of
      PNTTU on CTBs provides us the clue to design a potent inhibitor to prevent the
      CTS-induced impairment of CTB cells. 

PMID- 25050654
TI  - Risk-adjusted survival after coronary artery bypass grafting: implications for
      quality improvement.
AB  - Mortality represents an important outcome measure following coronary artery
      bypass grafting. Shorter survival times may reflect poor surgical quality and an
      increased number of costly postoperative complications. Quality control efforts
      aimed at increasing survival times may be misleading if not properly adjusted for
      case-mix severity. This paper demonstrates how to construct and cross-validate
      efficiency-outcome plots for a specified time (e.g., 6-month and 1-year survival)
      after coronary artery bypass grafting, accounting for baseline cardiovascular
      risk factors. The application of this approach to regional centers allows for the
      localization of risk stratification rather than applying overly broad and non
      specific models to their patient populations. 

PMID- 25050655
TI  - Evolving from reactive to proactive medicine: community lead (Pb) and clinical
      disparities in pre- and post-Katrina New Orleans.
AB  - In 2012 the U.S. Centers for Disease Control (CDC) set the blood Pb reference
      value at >=5 ug/dL. Clinical analysis of children's blood Pb levels is the common
      way to diagnose environmental Pb contamination, and intervention ensues with
      education and household dust cleanup. Recent review indicates that education and
      household dust cleanup are not effective at reducing children's Pb exposure. Here
      we review mapping environmental Pb and children's blood Pb response as an
      alternative approach for proactive Pb dust intervention. New Orleans was divided
      into a high (>=100 mg/kg) and low (<100 mg/kg) soil Pb communities. The
      children's blood Pb prevalence >=5 ug/dL for the high and low Pb domains were
      58.5% and 24.8% respectively pre-Katrina vs. 29.6% and 7.5% post-Katrina.
      Elevated soil Pb (mg/kg) and consequently Pb loading (ug/square area) permeates
      the high Pb domain and outdoor locations lack Pb dust safe play areas. The U.S.
      EPA 400 mg/kg soil Pb standard poses an outside Pb dust loading burden >37 times
      larger than allowed on interior residential floor environments. Environmental Pb
      dust is decreasing because of the transfer of large quantities of low Pb soil
      into selected communities. City-scale soil Pb mapping is an alternative
      diagnostic tool that provides information for planning proactive medicine to
      prevent clinical Pb exposure in the first place. 

PMID- 25050657
TI  - Epidemiological evaluation of notifications of environmental events in the State
      of Sao Paulo, Brazil.
AB  - Increasing urbanization across the globe, combined with an increased use of
      chemicals in various regions, contributes to several environmental events that
      influence environmental health. Measures that identify environmental factors and
      events should be introduced to facilitate epidemiological investigations by
      health services. The Brazilian Ministry of Health published a new list of
      notifiable diseases on 25 January 2011 and introduced environmental events as a
      new category of notifiable occurrences. The Center for Epidemiologic Surveillance
      in State of Sao Paulo, Brazil, created an online notification system that
      highlights "environmental events", such as exposure to chemical contaminants,
      drinking water with contaminants outside of the recommended range, contaminated
      air, and natural or anthropogenic disasters. This paper analyzed 300
      notifications received between May 2011 and May 2012. It reports the number of
      notifications with event classifications and analyzes the events relating to
      accidents with chemical substances. This paper describes the characteristics of
      the accidents that involved chemical substances, methods used, types of
      substances, exposed population, and measures adopted. The online notification of
      environmental events increases the analysis of the main events associated with
      diseases related to environmental chemicals; thus, it facilitates the adoption of
      public policies to prevent environmental health problems. 

PMID- 25050656
TI  - Health and health care disparities: the effect of social and environmental
      factors on individual and population health.
AB  - Recently the existence and prevalence of health and health care disparities has
      increased with accompanying research showing that minorities (African Americans,
      Hispanics/Latinos, Native Americans, and Pacific Islanders) are
      disproportionately affected resulting in poorer health outcomes compared to non
      minority populations (whites). This is due to multiple factors including and most
      importantly the social determinants of health which includes lower levels of
      education, overall lower socioeconomic status, inadequate and unsafe housing, and
      living in close proximity to environmental hazards; all contributing to poor
      health. Given the ever widening gap in health and health care disparities, the
      growing number of individuals living at or below the poverty level, the low
      number of college graduates and the growing shortage of health care professionals
      (especially minority) the goals of this paper are to: (1) Define diversity and
      inclusion as interdependent entities. (2) Review the health care system as it
      relates to barriers/problems within the system resulting in the unequal
      distribution of quality health care. (3) Examine institutional and global
      benefits of increasing diversity in research. (4) Provide recommendations on
      institutional culture change and developing a diverse culturally competent
      healthcare workforce. 

PMID- 25050659
TI  - Interdisciplinary medical social work: a working taxonomy.
AB  - Findings from a year-long exploratory study aimed at describing universal
      functions of medical social work with interdisciplinary teams in acute care
      settings are reported here. A universal taxonomy of interdisciplinary social work
      skills and competencies was empirically identified through a participatory action
      research framework. Findings support previous conceptual descriptions of medical
      social work's overarching and historical role to help interdisciplinary teams in
      acute care to consider patients' home environment, knowledge, beliefs, culture,
      and resources during assessment, treatment, and discharge planning. The
      empirically determined taxonomy reported is intended to provide social workers a
      framework with which to articulate and evaluate their core competencies on
      interdisciplinary medical teams. 

PMID- 25050658
TI  - Discussing cancer: communication with African Americans.
AB  - Regular screening for colorectal cancer (CRC) facilitates earlier detection,
      lowers mortality, and may reduce incidence through detection and removal of pre
      cancerous polyps. Optimizing health professional delivery of CRC screening
      information and recommendations can assist in reducing CRC disparity in the
      African-American community. This article presents qualitative data on African
      Americans' attitudes about health professional CRC communications based on the
      analysis of focus groups (N = 79). Using a social-ecological framework,
      colorectal cancer and professional communication themes are examined to offer
      four general and nine cancer-specific theoretically based and culturally
      appropriate strategies for improving health professional cancer communication
      with African Americans. 

PMID- 25050660
TI  - Interprofessional experiences and attitudes toward interprofessional health care
      teams among health sciences students.
AB  - This study examined how the interprofessional experience, including education and
      practice, affects graduate health science students' attitudes toward
      interprofessional practice in health care teams. Data were collected from 227
      graduate students, using the Attitudes toward Health Care Teams (ATHCT) scale.
      Both social work and other health science students had positive attitudes toward
      interprofessional collaboration with regard to its ability to improve the quality
      of a patient's care. The results from hierarchical linear regression analyses
      demonstrated that female students, older students, and students with longer
      interprofessional practice experiences had more positive attitudes toward
      interprofessional collaboration in health care teams. Based on these results,
      implications for interprofessional education are discussed. 

PMID- 25050661
TI  - A social work practice reflection on issues arising for LGBTI older people
      interfacing with health and residential care: rights, decision making and end-of
      life care.
AB  - This article is a social work practice reflection on issues arising for lesbian,
      gay, bisexual, transgender, and intersex (LGBTI) older people interfacing with
      health and residential care in Australia; focusing on clients, families, and
      carers in relation to rights, decision making, and end-of-life care. The article
      explores relevant case examples from social work practice in a health and
      residential care setting that highlight some specific complexities of working
      with this client group. This article brings greater attention to issues arising
      for older LBGTI when interfacing with health and residential care and has the
      potential to improve practice for social workers and other health professionals
      and improve outcomes for LGBTI older people. 

PMID- 25050662
TI  - Follow-up two years after diagnosis of diabetes in patients with psychosocial
      problems receiving an intervention by a medical social worker.
AB  - We followed up the psychosocial situation two years after diabetes diagnosis in
      patients (n = 82) aged 18-65 years, with psychosocial problems (PSP; n = 27) or
      not (NPSP; n = 55). We used a social questionnaire, the Hospital Anxiety and
      Depression scale (HAD), the Sense of Coherence scale (SOC), and the General
      Coping Questionnaire (GCQ). The PSP group had a more difficult situation with
      more strained economy, lower social support, more anxiety and depression, and
      lower SOC on both occasions. Being in the PSP group predicted experiencing a
      strong negative influence of the disease at follow-up. Regarding coping
      strategies, "problem focusing" decreased in both PSP and NPSP over time. "Social
      trust" and "intrusion" decreased only in NPSP. Otherwise the coping pattern was
      unchanged, with PSP showing lower scores on "self-trust" and "minimization" and
      higher scores on "protest," "isolation," and "intrusion." The most influenced
      areas at follow-up in the PSP group were work, relationship to partner and
      economy, and in the NPSP leisure-time activities, sexual life and work. Our
      findings underline the need to identify patients with psychosocial problems
      early. 

PMID- 25050664
TI  - The blue interpretation of art: the Blue Mosque.

PMID- 25050665
TI  - Being a neurosurgery specialist and a resident.

PMID- 25050663
TI  - ISO-66, a novel inhibitor of macrophage migration, shows efficacy in melanoma and
      colon cancer models.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory
      cytokine, which possesses a contributing role in cancer progression and
      metastasis and, thus, is now considered a promising anticancer drug target. Many
      MIF-inactivating strategies have proven successful in delaying cancer growth.
      Here, we report on the synthesis of ISO-66, a novel, highly stable, small
      molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The
      MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase
      active site of MIF, which has previously been shown to play an important role in
      its biological functions. In vitro, ISO-66 enhanced specific and non-specific
      anticancer immune responses, whereas prolonged administration of ISO-66 in mice
      with established syngeneic melanoma or colon cancer was non-toxic and resulted in
      a significant decrease in tumor burden. Subsequent ex vivo analysis of mouse
      splenocytes revealed that the observed decrease in tumor growth rates was likely
      mediated by the selective in vivo expansion of antitumor-reactive effector cells
      induced by ISO-66. Compared to other MIF-inactivating strategies employed in
      vivo, the anticancer activity of ISO-66 is demonstrated to be of equal or better
      efficacy. Our findings suggest that targeting MIF, via highly specific and stable
      compounds, such as ISO-66, may be effective for cancer treatment and stimulation
      of anticancer immune responses. 

PMID- 25050666
TI  - Which is more important for a surgeon: brain or hand?

PMID- 25050667
TI  - Kyphosis and review of the literature.
AB  - AIM: The term kyphosis is used to describe the spinal curve that results in an
      abnormally rounded back. Kyphosis may develop due to trauma, developmental
      anomalies, degenerative disc disease, inflammatory diseases, and infectious
      diseases and also iatrogenic. The aim of this paper is to review the
      etiopathognesis and the treatment management of kyphosis. METHODS: A search in
      the National Library of Medicine (Pubmed) database using key word 'kyphosis' and
      was made. For the literature review, papers concerning etiopathogenesis,
      classification and treatment were selected among these papers. RESULTS: A search
      in the National Library of Medicine (Pubmed) database using key word 'kyphosis'
      yielded 7506 papers published between 1916 and 2013. The main papers about
      kyphosis were congenital, Scheuermann, tumour related, neuromuscular,
      posttraumatic, infectionrelated, iatrogenic kyphosis. CONCLUSIONS: Every patient
      with kyphosis should be treated based on her/his current state and needs. It
      should always be remembered that the patients with negative sagittal balance can
      compensate it with the hip flexion but it is far more difficult to compensate the
      positive sagittal balance. The main goal of surgery to treat the kyphotic
      patients is to correct the sagittal curve and also restore a spinal balance
      within an acceptable range above the hips and knees.

PMID- 25050668
TI  - Biomechanics of neck injuries resulting from rear-end vehicle collisions.
AB  - It has been claimed that 85% of the neck injuries caused by car accidents are the
      result of rear-end collisions. This type of injury is called a whiplash injury,
      and its mechanisms are not completely understood due to the limited ability to
      diagnose them using X-ray or MRI. Biomechanical studies including research on
      injury mechanisms, injury criteria, neck kinematics and injury epidemiology were
      reviewed to investigate the details of whiplash injuries. Many different injury
      mechanisms has been studied and identified such as hyperextension of the neck,
      facet joint impingement, spine column pressure, and muscle strains. Possible
      injury criterions have been reported as The Neck Injury Criterion (NIC), Nij
      criterion, IV-NIC criterio, Nkm criterion, NDC criterion.

PMID- 25050669
TI  - CT-guided piriformis muscle injection for the treatment of piriformis syndrome.
AB  - AIM: Piriformis syndrome is a rare neuromuscular disorder that occurs when the
      piriformis muscle compresses or irritates the sciatic nerve. The treatment of
      piriformis syndrome includes injections into the piriformis muscle around the
      sciatic nerve. These invasive approaches have been used with various techniques
      to increase the safety of the procedure. Computed tomography (CT)-guided
      injection of the piriformis muscle and the clinical outcome of the patients are
      discussed. MATERIAL AND METHODS: The authors presented 10 consecutive patients
      that underwent CT-guided piriformis injection between March and December 2007.
      Three patients had a history of a severe fall on the buttocks, one had gluteal
      abscess formation following deep intramuscular injection, and another one had a
      habit of prolonged sitting on the carpet. Etiology was not identified in the
      other patients. Main complaints of the patients were pain and numbness in the
      legs. Hypesthesia was the major neurological finding. Magnetic resonance imaging
      (MRI) and electromyography (EMG) were performed in all patients. RESULTS: Nine
      patients had full and sustained recovery of their symptoms after piriformis
      injection. Only the patient who had gluteal abscess formation following deep
      intramuscular injection showed moderate improvement. Another patient was operated
      on in the 6th month after piriformis injection due to an extruded disc
      herniation. CONCLUSION: CT-guided piriformis injection is a safe and effective
      method in the treatment of piriformis syndrome.

PMID- 25050670
TI  - Neurotization of the phrenic nerve with accessory nerve for high cervical spinal
      cord injury with respiratory distress: an anatomic study.
AB  - AIM: High cervical spinal cord injury is associated with high morbidity and
      mortality. Traditional treatments carry various complications such as infection,
      pacemaker failure and undesirable movement. Thus, a secure surgical strategy with
      fewer complications analogous to physiological ventilation is still required. We
      hope to offer one potential method to decrease the complications and improve
      survival qualities of patients from the aspect of anatomy. The purpose of the
      study is to provide anatomic details on the accessory nerve and phrenic nerve for
      neurotization in patients with high spinal cord injuries. MATERIAL AND METHODS:
      38 cadavers (76 accessory and 76 phrenic nerves) were dissected in the study. The
      width, length and thickness of each accessory nerve and phrenic nerve above
      clavicle were measured. The distances from several landmarks on accessory nerve
      to the origin and the end of the phrenic nerve above clavicle were measured too.
      Then, the number of motor nerve fibers on different sections of the nerves was
      calculated using the technique of immunohistochemistry. RESULTS: The accessory
      nerves distal to its sternocleidomastoid muscular branches were 1.52 +/- 0.32 mm
      ~1.54 +/- 0.29 mm in width, 0.52 +/- 0.18 mm ~ 0.56 +/- 0.20mm in thickness and
      9.52 +/- 0.98 cm in length. And the phrenic nerves above clavicle were 1.44 +/-
      0.23 mm ~ 1.45 +/- 0.24 mm in width, 0.47 +/- 0.15 mm ~ 0.56 +/- 0.25 mm in
      thickness and 6.48 +/- 0.78 cm in length. The distance between the starting point
      of accessory nerve and phrenic nerve were 3.24 +/- 1.17 cm, and the distance
      between the starting point of accessory nerve and the end of the phrenic nerve
      above clavicle were 8.72 +/- 0.84 cm. The numbers of motor nerve fibers in
      accessory nerve were 1,038 +/- 320~1,102 +/- 216, before giving out the
      sternocleidomastoid muscular branches. The number of motor nerve fibers in the
      phrenic nerve was 911 +/- 321~1,338 +/- 467. CONCLUSION: The accessory nerve and
      the phrenic were similar in width, thickness and the number of motor nerve
      fibers. And the lengths of accessory nerve were long enough for neuritisation
      with phrenic nerve.

PMID- 25050671
TI  - Microsurgical anatomy and variations of the anterior clinoid process.
AB  - AIM: The aim of this study was to better define the microsurgical anatomy of the
      supra/parasellar region and describe variations of the anterior clinoid process
      (ACP). MATERIAL AND METHODS: Fifteen formalin-fixed cadaver heads and 25 dry
      skulls were used to define the microsurgical anatomy of the ACP and related
      structures. The presence of the caroticoclinoid foramen (CaCF) as well as other
      relevant measurements were all noted. Radiological examination of the CaCF was
      also demonstrated on dry skulls. RESULTS: Interosseous bridges, which form
      between the anterior and middle clinoid processes or connect all three (anterior,
      middle and posterior) clinoid processes, were found in 30% of the specimens. The
      average basal width, length and thickness of the ACP were 7.3 mm, 9.7 mm and 5.4
      mm, respectively. Length of the optic nerve (ON) up to the falciform ligament
      (FL) was 10.9 mm; length of the ON under the FL was 2.7 mm; length of ON after
      removal of the ACP and unroofing the optic canal was 21.1 mm. CONCLUSION: This
      study contributes to the relationship of important vascular, neural, bone and
      dural layers of this region and also demonstrates the variations of ACP by means
      of microsurgical dissections and radiological examinations.

PMID- 25050672
TI  - Chronic subdural hematoma: a comparison of recurrence rates following burr-hole
      craniostomy with and without drains.
AB  - AIM: To compare the rates of recurrence of chronic subdural hematoma following
      surgical evacuation by one of two methods, namely, using frontal and parietal
      burr holes without a drain or a single parietal burr hole with the addition of a
      subdural drain. MATERIAL AND METHODS: This was a randomized controlled trial with
      two groups of 70 patients each. Patients in group I had two burr holes and those
      in group II had a single burr-hole. A subdural drain was placed for the second
      group, and this was removed 48-72 hours later. Patients were followed up for 3
      months and symptomatic recurrences underwent re-exploration. RESULTS: 11 out of
      70 patients in group I had recurrent hematomas requiring surgery while only two
      out of 70 patients in group II had symptomatic recurrences. The difference was
      statistically significant (p=0.0168). CONCLUSION: The use of a single burr hole
      with drain appears to be a safe and effective procedure for the treatment of
      chronic subdural hematoma.

PMID- 25050673
TI  - Surgical treatment in sacral fractures and traumatic spinopelvic instabilities.
AB  - AIM: Sacral fractures are generally seen together with pelvic ring fractures.
      They can also develop in isolated form rarely. Instability is observed in these
      fractures in rates reaching 30%. MATERIAL AND METHODS: Spinopelvic stabilization
      was applied to 10 cases with pelvic fractures together with sacral fractures and
      spinopelvic instability. Two cases were treated with adductive screws extending
      from the iliac wing to the sacrum, 5 cases with standard lumboiliac instruments
      and 3 cases were treated with iliac wing plates that are our own design. The
      cases were evaluated according demographic data, VAS, ASIA and Oswestry scores
      and the types of the trauma and fracture. RESULTS: Six cases had unilateral
      sacroiliac instability while the instability was bilateral in 4 cases. Follow-up
      periods range between 6 and 91 months. Preoperative VAS was 8.4, Oswestry mean
      value was 91.2, postoperative late VAS was 2.2, and Oswestry was 24.4.
      CONCLUSION: Serious spinopelvic instability can be talked of in sacral fractures
      accompanied by pelvic fractures, particularly when the anterior and posterior
      integrity of the pelvic ring is interrupted together. An aggressive stabilization
      and fixation must be performed without delay.

PMID- 25050674
TI  - The effect of etanercept on spinal epidural fibrosis in a postlaminectomy rat
      model.
AB  - AIM: The formation of epidural fibrosis adjacent to the dura mater after
      posterior spinal surgery is a normal reaction of the body to surgery. Extensive
      epidural fibrosis is one of the important causes of postlaminectomy syndrome.
      Etanercept inhibits tumor necrosis factor-alpha and decreases fibroblast
      migration. Thus, etanercept prevents the formation of fibrosis. The aim of this
      study was to investigate the effects of topical application of etanercept on
      epidural fibrosis after laminectomy in a rat model. MATERIAL AND METHODS: Twenty
      four Wistar rats were equally and randomly divided into three groups (control,
      spongostan and etanercept). Laminectomy was performed between L3 and L5 in all
      the rats. Spongostan soaked with saline (0.1 mg/kg) and etanercept (300 MUg/kg)
      was directly exposed to and left on the dura mater. Four weeks later, the
      vertebral columns of the rats were removed en bloc between T10 and L5, and
      epidural fibrosis and arachnoidal involvement were evaluated and graded
      histopathologically. RESULTS: Our data revealed that epidural fibrosis was
      reduced significantly in the rats treated with etanercept, compared to the
      control groups (p < 0.05). CONCLUSION: Our study demonstrated that topical
      application of etanercept can be effective in reducing epidural fibrosis in rats
      after laminectomy.

PMID- 25050675
TI  - Robotic spine surgery: a preliminary report.
AB  - AIM: Robotic spine surgery techniques provide reduced pedicle screw malposition
      and radiation exposure during surgery. The aim of this study is to review
      clinical and radiological results of robotic spine surgery. MATERIAL AND METHODS:
      The preoperative, intraoperative and postoperative data for 27 patients were
      reviewed. To reveal the effect of a learning curve, the cases were divided into
      two groups: Group A and Group B The clinical data and radiological data were
      compared with the values obtained from preoperative planning. RESULTS: The
      patients consisted of 23 females and 4 males. A total of 136 screws were placed
      in the 27 cases. The accuracy rate of the screw positions was 98.5%. The overall
      mean procedure duration was 73.2 minutes for Group A and 46.1 minutes for Group
      B. The overall mean x-ray exposure time per screw was 1.3 seconds, 1.8 seconds
      for Group A and 0.9 seconds for Group B. Postoperative imaging revealed that 126
      screws were perfect, screw malposition of < 2mm was observed for 8 screws, and
      malposition of > 2mm was observed for 2 screws. CONCLUSION: Robotic spine surgery
      provides a high degree of accuracy for pedicle screw placement and allows for
      reduced radiation exposure.

PMID- 25050676
TI  - Early induction of ADAMTS 1, -4, -5 and -9 in IL-stimulated mouse astrocytes.
AB  - AIM: Astrocytes and extracellular matrix molecules have important roles in
      regulating synaptic functions between neurons in the central nervous system.
      However, under pathological conditions, these constituents are activated to form
      glial scar that is thought to be harmful for neuronal regeneration. The aim of
      this study was to evaluate the expression pattern of ADAMTS1, -4, -5 and -9 in IL
      1 stimulated astrocyte cultures obtained from postnatal day zero mouse brains.
      MATERIAL AND METHODS: Real time PCR analyses were performed. RESULTS: An
      overexpression of ADAMTS1, -4, -5 and -9 at the 3-h time point after IL-1
      stimulation was found. IL-1 stimulation induced aggrecaneses and this effect was
      time dependent. Maximum increase was detected at 3-h (six fold increase).
      Interestingly the expression of ADAMTS1 and -4 appeared to be at the highest
      expression level but the ADAMTS5 and ADAMTS9 expression level was much weaker
      (three times and two times respectively). CONCLUSION: To the best of our
      knowledge, this is the first report demonstrating induction of ADAMTS in IL-1
      induced astrocytes. Aggrecanases may play a role in tissue destruction in the
      progression of central nervous system (CNS) injury and they are differentially
      expressed in mouse CNS, suggesting a critical role in the pathogenesis of CNS
      injury. This can be a very crucial aetiologic factor for some neuropsychiatric
      disorders.

PMID- 25050677
TI  - Normal pressure hydrocephalus versus atrophic dilatation to distinguish and
      predict the benefits of surgical intervention with a phase-contrast MRI
      technique.
AB  - AIM: To compare mean cerebrospinal fluid (CSF) volume in the aqueduct by using
      phase-contrast magnetic resonance imaging for the patients with idiopathic normal
      pressure hydrocephalus (INPH) and atrophic dilation (AD) to investigate the
      efficacy of this technique in predicting surgery. MATERIAL AND METHODS: The MR
      images of a total of 80 individuals, consisting of 30 patients considered to have
      INPH, 20 patients with AD not proportional with cerebral sulci, and 30 control
      cases without a hydrocephalus clinical picture, were evaluated retrospectively.
      The minute mean aqueductal CSF flow rates of the three groups were compared using
      the Kruskall-Wallis analysis of variance, and the inter-group statistical
      comparisons were made using the Mann-Whitney U test. RESULTS: The mean aqueductal
      flow rates were 46.56 +/- 25.06 ml/min for the INPH group, 9.28 +/- 4.68 ml/min
      for the AD group, and 8.68 +/- 3.40 ml/min for the control group. The mean flow
      rate of the INPH group was significantly higher than those of the control and ADH
      groups (p < 0.001). CONCLUSION: The mean CSF flow rate may be useful in the
      diagnosis and differential diagnosis, and the prediction of the potential
      benefits of surgical intervention for patients considered to have INPH.

PMID- 25050678
TI  - Treatment principles for coccygodynia.
AB  - AIM: An evaluation of treatment methods and outcomes for coccygodynia cases that
      do not respond to conservative treatment. MATERIAL AND METHODS: Local anesthetic
      and steroid injections were applied in 32 coccygodynia cases that did not respond
      to conservative treatment (average of 15 months). Coccyx excision was performed
      as surgical treatment in 25 cases that had pain relief after the injections but
      later re-presented with complaints. The patients' pain levels were assessed with
      VAS. Postacchini classification was used for patient classification based on
      plain radiography. RESULTS: 20 (62%) of the cases (the total including injection
      and surgery groups) had a trauma history. Majority of the cases treated with
      local steroid injection included patients with Type I, while the 25 cases that
      received surgical treatment predominantly included Type II patients. One case had
      post-operative skin infection, which was treated with antibiotics. It was
      observed by comparing pre-operative and post-operative pain scores that both
      methods provided significant pain relief in all patients. CONCLUSION: While local
      steroid injection is an effective method of treatment for Type I patients, the
      coccyx removal is an effective method for controlling the pain in patients with
      trauma history and in Type II, III and IV patients.

PMID- 25050679
TI  - Combining pyramidal tract mapping, microscopic-based neuronavigation, and
      intraoperative magnetic resonance imaging improves outcome of epilepsy foci
      resection in the sensorimotor cortex.
AB  - AIM: To explore the clinical value of combining pyramidal tract mapping,
      microscopic-based neuronavigation, and intraoperative magnetic resonance imaging
      (iMRI) in the surgical treatment of epileptic foci involving sensorimotor cortex.
      MATERIAL AND METHODS: We retrospectively analyzed 69 patients with focal epilepsy
      involving motor and sensory cortex. The surgical operations in Group I (n=38)
      were performed under the guidance of conventional neuronavigation, and the
      operations of Group II (n=31) were aided by combining pyramidal tract mapping,
      microscopic-based neuronavigation and the iMRI technique. Chi square test was
      used to compare seizure outcome and neurological deficits across groups. RESULTS:
      7 patients (18.4%) in Group I, and 3 patients (9.7%) in Group II didn't recover
      to the level of preoperative strength within one year post-operation. The 2-year
      follow-up survey showed that more patients in Group II compared to Group I (71%
      vs. 55.3%, p=0.181) had a good outcome (Engel class I ~ II). CONCLUSION: The
      techniques of combining pyramidal tract mapping, microscopic-based
      neuronavigation and iMRI aid in precise mapping and hence resection of epileptic
      foci in sensorimotor cortex, which lead to improvement of surgical efficacy and
      significant reduction of postoperative loss of function.

PMID- 25050680
TI  - Occlusion of the ascending pharyngeal artery during carotid artery surgery:
      importance and technique.
AB  - AIM: In surgeries involving clamping, opening and repairing the carotid artery
      such as carotid endarterectomy (CEA) and proximal anastomosis at radial artery
      (RA) grafting, back-bleeding, often due to insufficient occlusion of the
      ascending pharyngeal artery (APA), must be avoided. In 96% of cases the APA
      originates at the dorsal side of the external carotid artery, while in 2% each it
      arises at the carotid bifurcation or the internal carotid artery. We developed a
      method to prevent back-bleeding from the APA irrespective of its origin. MATERIAL
      AND METHODS: For CEA we dissect the internal carotid artery and clamp the APA and
      the external carotid artery together. For RA grafting we dissect the external
      carotid artery and if the APA branches directly from this vessel, the APA is
      clamped directly. RESULTS: We used our new surgical technique in 54 cases (22 CEA
      and 32 RA grafts) and encountered no major back-bleeding. CONCLUSION: We consider
      this method to be simple and useful for improving the safety and success of
      carotid artery surgeries.

PMID- 25050681
TI  - The use of neuronavigation and intraoperative imaging systems in the surgical
      treatment of orbital tumors.
AB  - AIM: We aimed to show the effects of neuronavigation and intraoperative imaging
      systems on the surgical outcomes of orbital tumors. MATERIAL AND METHODS:
      Seventeen patients who underwent surgical treatment for orbital tumors by
      transcranial and transnasal approaches between 2008 and 2013 were analyzed
      retrospectively. Twelve of them were male and 5 were female. The mean age was
      41.6 years. Neuronavigation systems were used in all cases. Four patients were
      operated using intraoperative imaging systems. RESULTS: The transcranial approach
      was used in 9 (53%) patients, endoscopic medial orbital approach in 4 (23.5%),
      endoscopic inferolateral approach in 1 (6%), cranioorbitozygomatic approach in 1,
      lateral approach in 1, and the combined (medial endoscopic and lateral) approach
      in 1 patients. Total resection was achieved in 5 patients, gross total excision
      in 2, subtotal in 9 and partial in 1 patients. CONCLUSION: Modern technology has
      made a significant contribution to the treatment of orbital tumors. Although
      technological equipments facilitate the excision of tumors, the level of
      resection is mainly determined by the nature of tumor and adhesion to the
      adjacent neurovascular structures. It should not be forgotten that advanced
      technology never replaces a good anatomical knowledge and surgical experience,
      but has a complementary role.

PMID- 25050682
TI  - Occipitocervical fixation using occipital bone hooks and cervical lateral mass
      screws: analysis of 16 cases.
AB  - AIM: We present a series of 16 patients who underwent occipitocervical fixation
      with occipital bone hooks used as a substitute for occipital screws for the
      treatment of occipitocervical instability. MATERIAL AND METHODS: In this
      technique; instrumentation was started following the decompression with insertion
      of screws into lateral masses. At the occipital level, two symmetrical burr holes
      were drilled and two occipital bone hooks were inserted into each burr hole with
      an inverted position with respect to each other. Afterwards, rod-plates were
      placed and locked on the hooks and screw heads. Bone grafting was also performed
      to achieve a solid fusion. RESULTS: There were no neurological or vascular
      complications associated with this technique. No infection-related complications
      or hematomas were observed. Cerebro-spinal fluid leaks (CSF) occurred when the
      burr holes were drilled in 4 patients; however, these ceased when the occipital
      bone hooks were inserted. There were no cases of postoperative CSF fistula or
      pseudo-meningocele formation. No instrumentation problem was noted in any of the
      cases during the follow-up period. CONCLUSION: Relatively long term (average
      30.44 months) evaluation of the technique in terms of stability is satisfactory
      with no neurological, vascular or other major complications. However, further
      biomechanical studies are needed.

PMID- 25050683
TI  - Preliminary experience with squid: a new liquid embolizing agent for AVM, AV
      fistulas and tumors.
AB  - AIM: The aim of the present study was to analyze our experience with a new liquid
      embolic agent, Squid, for the treatment of cerebral vascular lesions. MATERIAL
      AND METHODS: We present 28 patients who were treated with two formulations of
      Squid (Squid 18 and Squid 12). The lesions included 16 arteriovenous malformation
      (AVM)s (Spetzler-Martin grade 2 in 8, 3 in 6 and 4 in 2), 9 arteriovenous (AV)
      fistulas, 2 tumors (glomus tumor and angiofibroma) and 1 AICA aneurysm. Of the 9
      patients presenting with hemorrhage, 6 were AVM, 2 were AVF and 1 was aneurysm.
      RESULTS: The total obliteration rate of the AVMs was 37.5%. Fistulas were closed
      completely after combined treatment with surgery in 6 out of 9 patients, and one
      was sent to radiotherapy. There was no mortality. Two reported hemorrhages and
      thromboembolic complications resulted in permanent deficits in 3 patients.
      Pathologic examination revealed mild inflammatory reaction with infiltration of
      polymorphonuclear cells in 5 patients in whom surgery was performed immediately
      after embolization. Technical problems such as rupture, inability to remove or
      premature occlusion of the microcatheter related to the embolic agent were not
      recorded. CONCLUSION: Squid is a safe and effective embolic agent for treatment
      of cerebral AVMs, AV fistulas, tumors and aneurysms with satisfactory
      obliteration rate.

PMID- 25050684
TI  - Intracranial basal cell carcinoma with extensive invasion of the skull base.
AB  - Intracranial invasion of basal cell carcinoma is very rare. A case of a 71-year
      old male patient is presented with extensive invasion of middle and posterior
      fossae, with nearly complete destruction of the petrous bone, involving
      cerebellopontine angle and cranial nerves by recurrent basal cell carcinoma of
      the auricular region on the right side. The clinical manifestation was
      cerebrospinal fluid otorrhoea, facial nerve palsy and trigeminal nerve impairment
      with hypoesthesia. The patient underwent surgery by combined retroauricular and
      temporal approach to the skull base. Adjuvant radiation of residual tumor and
      former tumor recurrence region was performed. MRI studies performed annually show
      no progress of the tumor. Our patient reports a good quality of life without new
      neurological deficits 6 years after surgery. Attention should be paid to the
      malignant nature of basal cell carcinoma making follow up care necessary. In
      indicated cases in which incomplete excision cannot be excepted and risk factors
      exist, follow up with CT or/and MRI should be performed to evaluate the
      infiltrative and invasive character of aggressive basal cell carcinoma and to
      rule out bone or cerebral infiltration. 

PMID- 25050686
TI  - Bubble over the head: Adeloye-Odeku disease in a Turkish child-case report.
AB  - Adeloye-Odeku disease is composed of dermoid cyst over anterior fontanelle, first
      described in 1971. We present an 11-year-old girl with a soft, fluctuant swelling
      over bregma. The lesion content was isointense to cerebrospinal fluid on both T2W
      and FLAIRW images. There was a lytic area under the lesion, seen on CT. The
      lesion was totally excised. Histopathology confirmed the diagnosis. The case was
      unique; because a fibrous band was observed extending to superior sagittal sinus
      and it has never been reported before. Although lesions are sub-aponeurotic,
      because of this kind of fibrous band, a thorough examination with neuroimaging
      tools is very important for planning of surgery. 

PMID- 25050685
TI  - Robotic assisted sacroplasty: a case report.
AB  - AIM: Sacral insufficiency fracture is an important cause of lower back and groin
      pain among the osteoporotic population. Diagnosis and treatment of SIFs are
      challenging. Currently, surgical treatment includes sacroplasty under C-arm
      fluoroscopy or computed tomography. Both techniques have a risk of accuracy and
      high radiation exposure. A sacral insufficiency fracture patient treated using
      robotic assisted surgery is presented and present literature is discussed.
      METHOD: A bilateral sacral insufficiency fracture patient with an additional L5
      osteoporotic vertebra fracture is treated by bilateral percutaneous
      vertebroplasty using robotic assisted surgery. RESULTS: Robotic assisted surgery
      provided less x-ray exposure to the patient and the surgeon with additional
      accuracy and comfort. CONCLUSION: Robotic assisted surgery in treatment of sacral
      insufficiency fracture can be an important alternative method.

PMID- 25050687
TI  - Gamma knife for obsessive compulsive disorder: can it be detrimental?
AB  - Functional neurological disorders (FND) have been a challenge to treat both for
      neurologists and neurosurgeons. Various ablative as well as non-ablative
      techniques have been used to treat these disorders. Gamma knife radiosurgery
      (GKRS) is also being practised to treat refractory obsessive- compulsive disorder
      (OCD). The subsequent complications of GKRS reported have been variable, with
      headache being the most common. We discuss here a rare complication of 'late
      onset radiation necrosis in bilateral caudate nuclei' in a patient after
      receiving GKRS three years back. This case highlights the need to be more
      cautious before administering ablative procedures in patients suffering with
      functional disorders.

PMID- 25050688
TI  - Coil embolization of intracranial aneurysms with ipsilateral carotid stenosis:
      technical considerations.
AB  - Simultaneous occurrence of carotid atherosclerotic disease and ipsilateral
      cerebral aneurysm is known because of common risk factors. When interventional
      neuroradiologists encounter such cases, issue of 'in which order to treat these
      lesions ' is raised. If carotid artery disease is treated first, then acute
      increase in perfusion pressure and high dose antiplatelets might increase the
      risk of aneurysm rupture. If aneurysm coiling is performed first, the stroke risk
      may increase due to manipulations through plaque and compromise of cerebral flow
      secondary to catheter placement through stenotic vessel. Even though aneurysm
      coiling first is a rational approach, there are technical problems like crossing
      the carotid lesion safely and making sure that placement of catheter through the
      stenosed vessel will not compromise the cerebral blood flow. This technical
      report describes our protocol in performing safe and successful coil embolization
      in three cases with moderate carotid stenosis and ipsilateral intracranial
      aneurysm. Our emphasis is mainly on technical considerations with the aim of
      avoiding cerebral embolism during crossing of carotid plaque and to avoid
      compromise of cerebral blood flow using 'syngo iflow'. These technical
      considerations may have important implications in treatment of intracranial
      aneurysm in patients with moderate ipsilateral cervical carotid stenosis.

PMID- 25050689
TI  - Retreatment of recanalized aneurysms after Y-stent-assisted coil embolization
      with double enterprise stents: case report and systematic review of the
      literature.
AB  - It is necessary to consider possibility of recanalization and retreatment after
      coil embolization for cerebral aneurysms. There is concern that retreatment for
      recanalized aneurysms after Y-stent-assisted coil embolization may be difficult
      because of double stents, especially in Y-stents with double closed-cell stents
      owing to narrowed structures. However, no detailed reports of retreatment after Y
      stent have been reported. Between July 2010 and June 2013, we treated four
      aneurysms with Y-stent-assisted coil embolization using Enterprise closed-cell
      stents. Recanalization occurred in one case (25%), and retreatment was performed.
      We easily navigated a microcatheter into the target portions of the aneurysm
      through the Y-stent and occluded the aneurysm with coils. Additionally, by
      systematically searching in PubMed, we found 105 cases of Y-stent-assisted coil
      embolization using Enterprise stents or Neuroform stents with more than 6 months
      of follow-up. Among them, retreatment was performed in 10 cases (9.5%). There
      were no significant differences in retreatment rates among different stent
      combinations (P=0.91; Fisher's exact test). In conclusion, navigation of a
      microcatheter into the aneurysm through the Y-stent with double Enterprise stents
      was feasible, and retreatment rates after Y-stent-assisted coiling may not depend
      on stent combinations. 

PMID- 25050690
TI  - One-stage operation for rare multiple mirror intracranial aneurysms: a case
      report and literature review.
AB  - Although intracranial multiple aneurysms are not uncommon, multiple mirror
      aneurysms are relatively rare. A few isolated cases have been described. However,
      to the best of our knowledge, 3 pairs of pure symmetrical mirror aneurysms in one
      patient have not been reported yet. We present a case of multiple mirror
      aneurysms involving the bilateral middle cerebral artery (MCA) bifurcations and
      posterior communicating arteries (P-com A) confirmation by one-stage operation.
      The possibility of one-stage treatment must be considered before surgery. Missed
      diagnosis and misdiagnosis must be avoided before one-stage operation for
      multiple mirror aneurysms. 

PMID- 25050691
TI  - Fragmentation to epidural space: first documented complication of Gelstix(TM.).
AB  - The knowledge of minimal invasive spinal surgery has increased greatly in recent
      years. A current issue is the hydrogel implant inserted through nucleus pulposus.
      In this paper we present a case in which the hydrogel implant was found to be
      fragmented into the spinal canal at follow up. The patient was a 40-year-old
      female. She was examined at another clinic because of low back pain about four
      months ago, and a hydrogel implant was inserted at the L5-S1 level. She was
      admitted to our clinic due to severe radicular pain. Magnetic resonance imaging
      (MRI) showed a posterolateral annular tear only and she was explored
      microneurosurgically as she did not benefit from a foraminal injection. A
      fragmented hydrogel implant that compressed the spinal root was seen
      peroperatively and it was excised. Postoperatively the radicular complaints of
      the patient disappeared and she was discharged with total recovery. Although
      rare, complications causing compression of neural structures can be seen after
      placing implants into the disc. In this case, the assessment of the patient
      according to the clinical presentation and microsurgical exploration if necessary
      are important. 

PMID- 25050692
TI  - Spinal arachnoid cysts associated with syringomyelia: a review of the literature
      and report of a case.
AB  - Syringomyelia is a not infrequent pathology that develops related to changes in
      cerebrospinal fluid dynamics due to many etiological factors. The development of
      syringomyelia through a spinal arachnoid cyst is quite rare and has been defined
      in only 31 cases in the literature. A case due to thoracic epidural lipomatosis
      has also been reported. There have been no previous reports of thoracic region
      epidural lipomatosis with underlying arachnoid cyst and syringomyelia as in our
      case. We present a 27-year-old patient who developed thoracic arachnoid cyst and
      underlying syringomyelia because of the pressure of the thoracic epidural fat
      tissue and also evaluate the characteristics of patients with syringomyelia by
      virtue of an arachnoid cyst previously reported in the literature. 

PMID- 25050693
TI  - Antibiotic-impregnated polymethylmethacrylate as an anterior biomechanical device
      for the treatment of cervical discitis and vertebral osteomyelitis: technical
      report of two cases.
AB  - AIM: To evaluate the feasibility of this novel surgical approach for treatment of
      cervical discitis and vertebral osteomyelitis. MATERIAL AND METHODS: This is a
      report of two patients who underwent anterior cervical decompression for discitis
      and vertebral osteomyelitis (DVO) with cervical spine reconstruction with
      polymethylmethacrylate impregnated with antibiotics (AI-PMMA). RESULTS: Both
      patients had successful procedures that were followed by 6 weeks of intravenous
      antibiotics. Stabilization and eradication of infection was achieved with
      clinical and radiographic stabilization seen in both. Follow-up is greater than
      18 months and both patients remain off antibiotics. CONCLUSION: The described
      technique using AI-PMMA offers immediate structural stability and local delivery
      of high concentration of antibiotics. Use in two patients has demonstrated a cost
      effective, long-term biomechanically stable construct and infection control.

PMID- 25050694
TI  - Posttraumatic syringomyelia: a technical note.
AB  - AIM: Previous studies have not identified a preferred surgical technique to treat
      posttraumatic syringomyelia. Both syringopleural shunting and arachnoidolysis are
      used in neurosurgery practice for the surgical treatment of posttraumatic
      syringomyelia. In this study, we present a new technique designed to achieve a
      better outcome following surgery. MATERIAL AND METHODS: A 33-year-old man, who
      exhibited pain and spasticity below the thoracic region after a traffic accident
      that occurred 16 years ago, was treated with a new technique. He also had
      paraparesis and urinary incontinency before the surgery. The initial
      cervicothoracic Magnetic Resonance Imaging (MRI) scans showed the development of
      a syrinx in the T4-5 region. A syringopleural shunt and bilateral subarachnoid to
      subarachnoid catheters from proximal to distal zones of the syrinx were performed
      under surgical microscope. RESULTS: The operative time was 90 minutes, and the
      blood loss was approximately 100 mL. The patient was mobilized on postoperative
      day 2 and was discharged 4 days after surgery with mild improvement of his
      preoperative symptoms. Postoperative MRI scans revealed partial regression at 6
      months and complete decompression of the syrinx at 3 years follow-up without any
      clinical symptoms. CONCLUSION: This is a report of minimal-access insertion
      combining syringopleural with subarachnoid-subarachnoid bypass shunt insertion.
      This minimally invasive technique seems to be an effective and safe method.

PMID- 25050695
TI  - Hormonal, metabolic, and cardiorespiratory responses of young and adult athletes
      to a single session of high-intensity cycle exercise.
AB  - This study aimed to determine the effects of a single high-intensity interval
      training (HIIT) session on salivary cortisol (SC) levels, physiological
      responses, and performance in trained boys and men. Twenty-three boys (11.5 +/-
      0.8 years) and 25 men (29.7 +/- 4.6 years) performed HIIT (4 consecutive Wingate
      Anaerobic Tests). SC in boys and men increased after HIIT from 5.55 +/- 3.3
      nmol/l to 15.13 +/- 9.7 nmol/l (+173%) and from 7.07 +/- 4.7 nmol/l to 19.19 +/-
      12.7 nmol/l (+171%), respectively (p < .01). Pretest SC as well as posttest
      changes were comparable in both groups (both p < .01). Peak blood lactate
      concentration was significantly lower in boys (12.6 +/- 3.5 mmol/l) than in men
      (16.3 +/- 3.1 mmol/l; p < .01). Throughout the HIIT, mean heart rates in boys
      were higher (p < .001) but relative peak oxygen uptake (ml.min-1.kg-1; p < .05)
      and performance were lower (p < .001) in boys than in men. HIIT in young athletes
      is associated with a higher activation of the hormonal stress axis than other
      types of exercise regimes as described in the literature. This study is the first
      to show a pronounced SC increase to HIIT in trained boys accompanied by elevated
      levels of blood lactate concentrations and heart rate suggesting a high cardio
      respiratory, metabolic, and hormonal response to HIIT in 11-year-old boys. 

PMID- 25050696
TI  - Half-sandwich scandium boryl complexes bearing a silylene-linked cyclopentadienyl
      amido ligand.
AB  - A boryl scandium complex supported by the silylene-linked cyclopentadienyl-amido
      ligand was synthesized for the first time, which on reaction with nitric oxide
      (NO) afforded a novel scandium boryldiazeniumdiolate [ON(boryl)NO] complex. 

PMID- 25050697
TI  - Tuning molecular weights of Bombyx mori (B. mori) silk sericin to modify its
      assembly structures and materials formation.
AB  - Bombyx mori (B. mori) silk sericin is a protein with features desirable as a
      biomaterial, such as increased hydrophilicity and biodegradation, as well as
      resistance to oxidation, bacteria, and ultraviolet light. In contrast to other
      widely studied B. mori silk proteins such as fibroin, sericin is still unexplored
      as a building block for fabricating biomaterial, and thus a facile technique of
      processing it into a material is needed. Here, electrospinning technology was
      used to fabricate it into biomaterials from two forms of B. mori silk sericin
      with different molecular weights, one is a low (12.0 kDa) molecular sericin (LS)
      form and another is a high (66.0 kDa) molecular weight sericin (HS) form.
      Circular dichroism (CD) spectra showed that LS in hexafluoroacetone (HFA) solvent
      adopted a predominantly random coil conformation, whereas HS tended to form a
      beta-sheet structure along with a large content of random coils. In addition, LS
      and HS in HFA solvent were found to form cylinder-like smaller nanoparticles and
      larger irregular aggregates before electrospinning, respectively. As a result,
      biomaterials based on microparticles and nanofibers were successfully fabricated
      by electrospinning of LS and HS dissolved in HFA, respectively. The cell
      viability and differentiation assay indicated that nanofibers and microparticles
      improved cell adhesion, growth, and differentiation, proving that the scaffolds
      electrospun from sericin are biocompatible regardless of its molecular weight.
      The microparticles, not common in electrospinning of silk proteins reported
      previously, were found to promote the osteogenic differentiation of mesenchymal
      stem cells in comparison to the nanofibers. This study suggested that molecular
      weight of sericin mediates its secondary structure and assembly structure, which
      in turn leads to a control of final morphology of the electrospun materials. The
      microparticles and nanofibers of sericin can be potentially used as building
      blocks for fabricating the scaffolds for tissue engineering. 

PMID- 25050698
TI  - The cancer mortality and incidence experience of workers at British Nuclear Fuels
      plc, 1946-2005.
AB  - The aim of this study was to estimate cancer mortality and incidence risk
      associated with external radiation exposure in the BNFL cohort of nuclear workers
      and to determine if these risks are modified by potential for internal exposure.
      The cohort comprised 64,956 individuals who were employed at the four study sites
      between 1946 and 2002, followed up to 2005. External radiation exposures as
      measured by personal dosimeters (generally 'film badges') were available for
      42,431 individuals classified as 'radiation workers'. Poisson regression models
      were used to investigate cancer mortality and incidence in relation to cumulative
      external radiation exposure using relative risk models. The cohort showed the
      expected 'healthy worker' effect. This analysis found an increased risk of all
      cancers associated with external occupational radiation exposure (ERR/Gy = 0.34
      90% CI: 0.07; 0.64), with significant excess risks observed for all solid cancers
      (ERR/Gy = 0.29 90% CI: 0.02; 0.59) and leukaemia excluding CLL (ERR/Gy = 2.60 90%
      CI: 0.28; 7.01). The overall cancer risk estimates are consistent with values
      used by national and international bodies in setting radiation protection
      standards. The slopes of the dose response relationships for all cancer mortality
      and incidence were found to be significantly less steep for workers exposed to
      both external radiation and potentially to internal radiation (ERR/Gy = 0.09 90%
      CI: -0.17; 0.39) when compared to those workers only exposed to external
      radiation (ERR/Gy = 1.14 90% CI: 0.49; 1.89). Analyses of individual cancer types
      indicate that this overall result is mainly driven by that for digestive cancers
      and in particular cancers of the oesophagus. Categorical analyses also revealed
      that the difference in the dose response relationship between the two groups is
      only apparent for those exposed to cumulative external doses in excess of 200
      mGy. Such differences have also been observed for non-cancer mortality outcomes
      in this cohort. Further work is required to explain these differences; for
      example, whether they may result from confounding by internal organ dose or
      lifestyle factors associated with socio-economic status.

PMID- 25050699
TI  - The volume of hydration in terminally ill cancer patients with hydration-related
      symptoms: a prospective study.
AB  - BACKGROUND: Recently, there has been a growing interest in the use of artificial
      hydration therapy (AHT) for terminally ill cancer patients. Some studies have
      demonstrated that appropriate hydration can contribute to patient comfort;
      however, few studies have examined the effects of volume reduction on patient
      symptoms and quality of life (QOL). OBJECTIVE: This study aimed to clarify the
      effects of reducing the volume of artificial hydration based on the Japanese
      guideline in terminally ill cancer patients with hydration-related symptoms on
      the alleviation of various symptoms and QOL. METHODS: Of the 273 terminally ill
      cancer patients who were transferred from other hospitals for palliative care
      over the last 2 years, 78 patients who presented with hydration-related symptoms
      at the time of admission were analyzed. We performed guideline-based AHT and
      reduced the volume of hydration with standard pharmacological therapy. The
      effects on the alleviation of hydration-related symptoms and QOL were examined
      using a numeric rating scale and item 30 of the European Organization for
      Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (EORTC QLQ
      C30) to compare values measured before and one week after AHT. We also evaluated
      patient satisfaction and the feeling of benefit from hydration one week after the
      study commenced. RESULTS: Hydration-related symptoms (nausea, 16 cases; abdominal
      pain/distention, 22 cases; peripheral edema, 32 cases; and dyspnea, 15 cases)
      were significantly improved after performing guideline-based AHT (p=0.024,
      p=0.003, p<0.0001, and p=0.046, respectively). General QOL scores, global
      satisfaction, and feeling of benefit were also significantly improved after
      performing guideline-based AHT (p<0.0001, p=0.0001, and p=0.001, respectively).
      CONCLUSIONS: The provision of appropriate guideline-based AHT can contribute to
      alleviating hydration-related symptoms and improving QOL in terminally ill cancer
      patients.

PMID- 25050701
TI  - A simple method for simultaneous quantification of total arabinoxylans and
      fructans in wheat flour.
AB  - Current methods for measuring fructan and arabinoxylan concentrations in wheat
      flour are time-consuming, and each type of the polymers requires a separate
      method. Here, we report the development of a new method that allows simultaneous
      determination of arabinoxylan and fructan contents in wheat flour. The new method
      is based on a single hydrolysis procedure for both arabinoxylans and fructans and
      an optimized separation technique for all monomers released. Owing to the use of
      milder hydrolysis conditions that afforded higher recovery of pentoses, the level
      of arabinoxylans in wheat flour determined by this new method is slightly higher
      than that measured with the widely used hydrolysis protocol. On the basis of the
      finding that, for a given flour sample, the total fructose concentration after
      hydrolysis is highly correlated with its total fructan concentration, the fructan
      content of a wheat flour sample can thus be estimated directly by the total
      fructose content. By simplifying and combining the two separate methods used for
      arabonoxylan and fructan analysis, this new method enables the quantification of
      arabinoxylans and fructans in wheat flour using a single acid hydrolysis step and
      a single high-performance liquid chromatography run. 

PMID- 25050702
TI  - Heat shock proteins in relation to heat stress tolerance of creeping bentgrass at
      different N levels.
AB  - Heat stress is a primary factor causing summer bentgrass decline. Changes in gene
      expression at the transcriptional and/or translational level are thought to be a
      fundamental mechanism in plant response to environmental stresses. Heat stress
      redirects protein synthesis in higher plants and results in stress protein
      synthesis, particularly heat shock proteins (HSPs). The goal of this work was to
      analyze the expression pattern of major HSPs in creeping bentgrass (Agrostis
      stolonifera L.) during different heat stress periods and to study the influence
      of nitrogen (N) on the HSP expression patterns. A growth chamber study on 'Penn
      A4' creeping bentgrass subjected to 38/28 degrees C day/night for 50 days, was
      conducted with four nitrate rates (no N-0, low N-2.5, medium N-7.5, and high N
      12.5 kg N ha-1) applied biweekly. Visual turfgrass quality (TQ), normalized
      difference vegetation index (NDVI), photochemical efficiency of photosystem II
      (Fv/Fm), shoot electrolyte leakage (ShEL), and root viability (RV) were
      monitored, along with the expression pattern of HSPs. There was no difference in
      measured parameters between treatments until week seven, except TQ at week five.
      At week seven, grass at medium N had better TQ, NDVI, and Fv/Fm accompanied by
      lower ShEL and higher RV, suggesting a major role in improved heat tolerance. All
      the investigated HSPs (HSP101, HSP90, HSP70, and sHSPs) were up-regulated by heat
      stress. Their expression patterns indicated cooperation between different HSPs
      and their roles in bentgrass thermotolerance. In addition, their production seems
      to be resource dependent. This study could further improve our understanding
      about how different N levels affect bentgrass thermotolerance. 

PMID- 25050704
TI  - The effects of CAMPATH-1H on cell viability do not correlate to the CD52 density
      on the cell surface.
AB  - Graft versus host disease (GvHD) is one of the main complications after
      hematological stem cell transplantation (HSCT). CAMPATH-1H is used in the pre
      transplant conditioning regimen to effectively reduce GvHD by targeting CD52
      antigens on T cells resulting in their depletion. Information regarding CD52
      expression and the effects of CAMPATH-1H on immune cells is scant and limited to
      peripheral blood (PB) T and B cells. To date, the effects of CAMPATH-1H on cord
      blood (CB) cells has not been studied. Here we aimed to analyze CD52 expression
      and the effects of CAMPATH-1H on fresh or frozen, resting or activated, PB
      mononuclear cells (PBMC) and CB mononuclear cells (CBMC). In resting state, CD52
      expression was higher in CB than PB T cell subsets (653.66 +/- 26.68 vs 453.32 +/
      19.2) and B cells (622.2+/-20.65 vs 612.0 +/- 9.101) except for natural killer
      (NK) cells where CD52 levels were higher in PB (421.0 +/- 9.857) than CB (334.3
      +/- 9.559). In contrast, CD52 levels were comparable across all cell types after
      activation. CAMPATH-1H depleted resting cells more effectively than activated
      cells with approximately 80-95% of apoptosis observed with low levels of
      necrosis. There was no direct correlation between cell surface CD52 density and
      depleting effects of CAMPATH-1H. In addition, no difference in cell viability was
      noted when different concentrations of CAMPATH-1H were used. CD52 was not
      expressed on HSC but began to be expressed as the cells differentiate, implying
      that CAMPATH-1H could potentially affect HSC differentiation and proliferation.
      Our study provides insightful information, which contributes to the better
      understanding in the use of CAMPATH-1H as part of the conditioning regime in
      HSCT.

PMID- 25050703
TI  - Controlling malaria using livestock-based interventions: a one health approach.
AB  - Where malaria is transmitted by zoophilic vectors, two types of malaria control
      strategies have been proposed based on animals: using livestock to divert vector
      biting from people (zooprophylaxis) or as baits to attract vectors to insecticide
      sources (insecticide-treated livestock). Opposing findings have been obtained on
      malaria zooprophylaxis, and despite the success of an insecticide-treated
      livestock trial in Pakistan, where malaria vectors are highly zoophilic, its
      effectiveness is yet to be formally tested in Africa where vectors are more
      anthropophilic. This study aims to clarify the different effects of livestock on
      malaria and to understand under what circumstances livestock-based interventions
      could play a role in malaria control programmes. This was explored by developing
      a mathematical model and combining it with data from Pakistan and Ethiopia.
      Consistent with previous work, a zooprophylactic effect of untreated livestock is
      predicted in two situations: if vector population density does not increase with
      livestock introduction, or if livestock numbers and availability to vectors are
      sufficiently high such that the increase in vector density is counteracted by the
      diversion of bites from humans to animals. Although, as expected, insecticide
      treatment of livestock is predicted to be more beneficial in settings with highly
      zoophilic vectors, like South Asia, we find that the intervention could also
      considerably decrease malaria transmission in regions with more anthropophilic
      vectors, like Anopheles arabiensis in Africa, under specific circumstances: high
      treatment coverage of the livestock population, using a product with stronger or
      longer lasting insecticidal effect than in the Pakistan trial, and with small
      (ideally null) repellency effect, or if increasing the attractiveness of treated
      livestock to malaria vectors. The results suggest these are the most appropriate
      conditions for field testing insecticide-treated livestock in an Africa region
      with moderately zoophilic vectors, where this intervention could contribute to
      the integrated control of malaria and livestock diseases. 

PMID- 25050705
TI  - Age-related differences in bitter taste and efficacy of bitter blockers.
AB  - BACKGROUND: Bitter taste is the primary culprit for rejection of pediatric liquid
      medications. We probed the underlying biology of bitter sensing and the efficacy
      of two known bitter blockers in children and adults. METHODS: A racially diverse
      group of 154 children (3-10 years old) and their mothers (N = 118) evaluated the
      effectiveness of two bitter blockers, sodium gluconate (NaG) and monosodium
      glutamate (MSG), for five food-grade bitter compounds (quinine, denatonium
      benzoate, caffeine, propylthiouracil (PROP), urea) using a forced-choice method
      of paired comparisons. The trial was registered at clinicaltrials.gov
      (NCT01407939). RESULTS: The blockers reduced bitterness in 7 of 10 bitter-blocker
      combinations for adults but only 3 of 10 for children, suggesting that efficacy
      depends on age and is also specific to each bitter-blocker combination. Only the
      bitterness of urea was reduced by both blockers in both age groups, whereas the
      bitterness of PROP was not reduced by either blocker in either age group
      regardless of TAS2R38 genotype. Children liked the salty taste of the blocker NaG
      more than did adults, but both groups liked the savory taste of MSG equally.
      CONCLUSIONS AND RELEVANCE: Bitter blocking was less effective in children, and
      the efficacy of blocking was both age and compound specific. This knowledge will
      pave the way for evidence-based strategies to help develop better-tasting
      medicines and highlights the conclusion that adult panelists and genotyping alone
      may not always be appropriate in evaluating the taste of a drug geared for
      children.

PMID- 25050706
TI  - Dual specificity and novel structural folding of yeast phosphodiesterase-1 for
      hydrolysis of second messengers cyclic adenosine and guanosine 3',5'
      monophosphate.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) decompose second messengers cAMP and
      cGMP that play critical roles in many physiological processes. PDE1 of
      Saccharomyces cerevisiae has been subcloned and expressed in Escherichia coli.
      Recombinant yPDE1 has a KM of 110 MUM and a kcat of 16.9 s(-1) for cAMP and a KM
      of 105 MUM and a kcat of 11.8 s(-1) for cGMP. Thus, the specificity constant
      (kcat/KM(cAMP))/(kcat/KM(cGMP)) of 1.4 indicates a dual specificity of yPDE1 for
      hydrolysis of both cAMP and cGMP. The crystal structures of unliganded yPDE1 and
      its complex with GMP at 1.31 A resolution reveal a new structural folding that is
      different from those of human PDEs but is partially similar to that of some other
      metalloenzymes such as metallo-beta-lactamase. In spite of their different
      structures and divalent metals, yPDE1 and human PDEs may share a common mechanism
      for hydrolysis of cAMP and cGMP. 

PMID- 25050708
TI  - Neuropsychological outcome after complicated Shiga toxin-producing Escherichia
      coli infection.
AB  - BACKGROUND: The diarrhea associated hemolytic uremic syndrome (HUS) is a major
      cause of acute uremic failure in children, but not very common in adults. The
      enterohaemorrhagic Escherichia coli-epidemic in Germany in 2011 affected mostly
      young and healthy adults. While their immediate deficits have been published, not
      much is known about the time course and degree of recovery concerning cognitive
      and behavioral impairment. METHODS AND FINDINGS: Twenty patients with Shiga toxin
      producing Escherichia coli infection and neurological symptoms underwent
      comprehensive neuropsychological assessment 3 months and 1 year after the acute
      disease. Overall, there was an excellent recovery of cognitive functions. In a
      detailed neuropsychological analysis no significant deficits could be noticed 1
      year after the infection in terms of cognitive function, alertness, executive
      functions and speech. Interestingly there were no correlations between different
      indicators for severity of disease (hemoglobin and creatinine levels, days of
      hospitalization, neurological symptoms and MRI changes) and neuropsychological
      outcome. However, there were a small number of patients with limitations in every
      day and professional life even one year after the acute disease. CONCLUSIONS: Our
      study does not provide definitive answers regarding risk factors for these
      limitations. Still since Shiga toxin -producing Escherichia coli infection is a
      rare condition in adults, the information this study provides is important for
      the clinical practice. On one hand for consulting patients and on the other to
      raise the awareness of the physicians to possible long term complains and the
      consideration of neuropsychological assessment and supportive psychological
      treatment.

PMID- 25050709
TI  - fcGENE: a versatile tool for processing and transforming SNP datasets.
AB  - BACKGROUND: Modern analysis of high-dimensional SNP data requires a number of
      biometrical and statistical methods such as pre-processing, analysis of
      population structure, association analysis and genotype imputation. Software used
      for these purposes often rely on specific and incompatible input and output data
      formats. Therefore extensive data management including multiple format
      conversions is necessary during analyses. METHODS: In order to support fast and
      efficient management and bio-statistical quality control of high-dimensional SNP
      data, we developed the publically available software fcGENE using C++ object
      oriented programming language. This software simplifies and automates the use of
      different existing analysis packages, especially during the workflow of genotype
      imputations and corresponding analyses. RESULTS: fcGENE transforms SNP data and
      imputation results into different formats required for a large variety of
      analysis packages such as PLINK, SNPTEST, HAPLOVIEW, EIGENSOFT, GenABEL and tools
      used for genotype imputation such as MaCH, IMPUTE, BEAGLE and others. Data
      Management tasks like merging, splitting, extracting SNP and pedigree information
      can be performed. fcGENE also supports a number of bio-statistical quality
      control processes and quality based filtering processes at SNP- and sample-wise
      level. The tool also generates templates of commands required to run specific
      software packages, especially those required for genotype imputation. We
      demonstrate the functionality of fcGENE by example workflows of SNP data analyses
      and provide a comprehensive manual of commands, options and applications.
      CONCLUSIONS: We have developed a user-friendly open-source software fcGENE, which
      comprehensively supports SNP data management, quality control and analysis
      workflows. Download statistics and corresponding feedbacks indicate that software
      is highly recognised and extensively applied by the scientific community.

PMID- 25050710
TI  - Species-specific responses to community density in an unproductive perennial
      plant community.
AB  - Most studies of density dependent regulation in plants consider a single target
      species, but regulation may also occur at the level of the entire community.
      Knowing whether a community is at carrying capacity is essential for
      understanding its behaviour because low density plant communities may behave
      quite differently than their high density counterparts. Also, because the
      intensity of density dependence may differ considerably between species and
      physical environments, generalizations about its effects on community structure
      requires comparisons under a range of conditions. We tested if: (1) density
      dependent regulation occurs at the level of an entire plant community as well as
      within individual species; (2) the intensity (effect of increasing community
      density on mean plant mass) and importance (the effect of increasing density,
      relative to other factors, on mean plant mass) of competition increases,
      decreases or remains unchanged with increasing fertilization; (3) there are
      species-specific responses to changes in community density and productivity. In
      63 1 m2 plots, we manipulated the abundance of the nine most common species by
      transplanting or removing them to create a series of Initial Community Densities
      above and below the average natural field density, such that the relative
      proportion of species was consistent for all densities. Plots were randomly
      assigned to one of three fertilizer levels. At the community level, negative
      density dependence of mean plant size was observed for each of the 4 years of the
      study and both the intensity and importance of competition increased each year.
      At the species level, most species' mean plant mass were negatively density
      dependent. Fertilizer had a significant effect only in the final year when it had
      a negative effect on mean plant mass. Our data demonstrate a yield-density
      response at the entire community-level using perennial plant species in a multi
      year experiment. 

PMID- 25050712
TI  - Making sense of Brownian motion: colloid characterization by dynamic light
      scattering.
AB  - Dynamic light scattering (DLS) has evolved as a fast, convenient tool for
      particle size analysis of noninteracting spherical colloids. In this historical
      review, we discuss the basic principle, data analysis, and important precautions
      to be taken while analyzing colloids using DLS. The effect of particle
      interaction, polydispersity, anisotropy, light absorption, and so forth, on
      measured diffusion coefficient is discussed. New developments in this area such
      as diffusing wave spectroscopy, particle tracking analysis, microrheological
      studies using DLS, and so forth, are discussed in a manner that can be understood
      by a beginner. 

PMID- 25050711
TI  - Estimating cognitive reserve in healthy adults using the Cognitive Reserve Scale.
AB  - The concept of cognitive reserve emerged from observed disparities between brain
      pathology and clinical symptoms. It may explain better neuropsychological
      performance in healthy individuals. The objectives of this study were to measure
      reserve in healthy subjects using a new Cognitive Reserve Scale (CRS), analyze
      the internal consistency of the CRS, and analyze validity evidence. A total of
      117 healthy individuals were divided into two groups: 87 adults (aged 18-64
      years) and 30 elderly adults (>=65 years). All subjects completed the CRS and a
      comprehensive neuropsychological battery. The internal consistency of the scale
      was satisfactory (alpha = 0.77). No significant differences were observed between
      genders (t = 0.51, p = 0.611), and age was corrected by averaging the CRS score.
      The study of validity evidence showed that education affected the CRS (t = -2.98,
      p = 0.004, partial h2 = 0.07) and there was no significant relationship between
      the CRS and IQ (r = 0.09, p = 0.33). Occupational attainment and the CRS were not
      related (F2,116 = 0.11, p = 0.898). In line with previous studies on reserve,
      heterogeneity was observed in the analyses of relationships between the CRS and
      cognitive performance. There were significant relationships between CRS score and
      the Verbal Learning Spanish-Complutense Test last trial (r = 0.24, p = 0.009),
      sum (r = 0.32, p = 0.000), short-term (r = 0.29, p = 0.002) and long-term memory
      (r = 0.22, p = 0.018), Matrix Reasoning subtest (r = 0.20, p = 0.027) and Block
      Design subtest (r = 0.20, p = 0.029). No other neuropsychological variables
      correlated with the CRS (p>0.05). The CRS is a reliable instrument that reflects
      the frequency of participation in brain-stimulating activities across the
      lifetime. The associations between the CRS and education and neuropsychological
      performance support validity evidence. 

PMID- 25050714
TI  - Immune therapy for liver cancer.

PMID- 25050715
TI  - Antiparasitic drug reverses neurodevelopmental deficits.

PMID- 25050717
TI  - With oxytocin, old muscles act like new.

PMID- 25050718
TI  - The social benefits of concealing illness.

PMID- 25050720
TI  - Sea urchins point the way.

PMID- 25050721
TI  - Animal care and use programs for multiple campuses.

PMID- 25050722
TI  - Separate institutions.

PMID- 25050723
TI  - Possible, but prudent?

PMID- 25050724
TI  - Multiple IOs with full authority.

PMID- 25050725
TI  - A word from OLAW and USDA.

PMID- 25050727
TI  - Idiopathic cutaneous xanthoma in a pet rabbit.

PMID- 25050728
TI  - Evaluation of the neutrophil-lymphocyte ratio as a measure of distress in rats.
AB  - The ability to evaluate distress in laboratory animals is needed in order to
      ensure that husbandry and experimental procedures do not negatively impact animal
      welfare. Accurate measurement of acute stress and chronic stress, and
      distinguishing between stress that is harmful (distress) and stress that does no
      harm (eustress), can be challenging. Whereas corticosterone concentrations are
      commonly used to measure stress in laboratory animals, the neutrophil-lymphocyte
      ratio has been proposed as a potentially better indicator of chronic stress.
      Furthermore, an association between such measures of stress and concurrent
      behavioral indicators of negative welfare is required to determine their accuracy
      in evaluating distress. The authors compared serum corticosterone concentrations
      and neutrophil-lymphocyte ratios to assess acute or chronic stress in male
      Sprague Dawley rats. Elevated serum corticosterone concentrations, but not
      neutrophil-lymphocyte ratios, were associated with acute stress exposure, whereas
      elevated neutrophil-lymphocyte ratios, but not serum corticosterone
      concentrations, were associated with chronic stress exposure. Because the
      neutrophil-lymphocyte ratio differences corresponded with a behavioral indicator
      of distress in chronically stressed rats, it may serve as a valuable tool for the
      physiological assessment of distress in rats. 

PMID- 25050729
TI  - Shutting down a working vivarium for decontamination.
AB  - Handling a rodent disease outbreak in a facility can be a challenge. After the
      University of Colorado Denver Office of Laboratory Animal Resources enhanced its
      sentinel monitoring program, > 90% of the animal colonies housed in a vivarium at
      the Anschutz Medical Campus (with an area of 50,000 net ft(2)), serving the labs
      of > 250 principal investigators, tested positive for multiple infective agents
      including mouse parvovirus, fur mites, pinworms and epizootic diarrhea of infant
      mice. The authors detail the process by which they planned and executed a
      shutdown and a decontamination of the facility, which involved the rederivation
      or cryopreservation of > 400 unique genetically modified mouse lines. The authors
      discuss the aspects of the project that were successful as well as those that
      could have been improved. 

PMID- 25050730
TI  - Engaging students to participate.

PMID- 25050731
TI  - Make a wish.

PMID- 25050732
TI  - Advancing proficiency in animal surgery.
AB  - Dr. Perret-Gentil describes how he went from being a military veterinarian to
      being a specialist in laboratory animal surgery and discusses the importance of
      adequate training in surgical techniques for maintaining animal welfare.

PMID- 25050735
TI  - Response to the Bam earthquake: a qualitative study on the experiences of the top
      and middle level health managers in Kerman, Iran.
AB  - INTRODUCTION: The 2003 Bam, Iran earthquake resulted in high casualties and
      required international and national assistance. This study explored local top and
      middle level managers' disaster relief experiences in the aftermath of the Bam
      earthquake. METHODS: Using qualitative interview methodology, top and middle
      level health managers employed during the Bam earthquake were identified. Data
      were collected via in-depth interviews with participants. Data were analysed
      using thematic analysis. RESULTS: Results showed that the managers interviewed
      experienced two main problems. First, inadequacy of preparation of local health
      organisations, which was due to lack of familiarity of the needs, unavailability
      of essential needs, and also increasing demands, which were above the
      participants' expectations. Second, inappropriateness of delivered donations was
      perceived as a problem; for example, foods and sanitary materials were either
      poor quality or expired by date recommended for use. Participants also found
      international teams to be more well-equipped and organised. CONCLUSIONS: During
      the disaster relief period of the response to the Bam earthquake, local health
      organizations were ill prepared for the event. In addition, donations delivered
      for relief were often poor quality or expired beyond a usable date.

PMID- 25050734
TI  - Effects of HIV infection on the metabolic and hormonal status of children with
      severe acute malnutrition.
AB  - BACKGROUND: HIV infection occurs in 30% of children with severe acute
      malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and
      recovery from malnutrition are poorly understood. METHODS: We conducted a
      prospective cohort study of 75 severely malnourished Ugandan children. HIV
      status/CD4 counts were assessed at baseline; auxologic data and blood samples
      were obtained at admission and after 14 days of inpatient treatment. We utilized
      metabolomic profiling to characterize effects of HIV infection on metabolic
      status and subsequent responses to nutritional therapy. FINDINGS: At admission,
      patients (mean age 16.3 mo) had growth failure (mean W/H z-score -4.27 in non
      edematous patients) that improved with formula feeding (mean increase 1.00). 24%
      (18/75) were HIV-infected. Nine children died within the first 14 days of
      hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR =
      8.83). HIV-infected and HIV-negative children presented with elevated NEFA,
      ketones, and even-numbered acylcarnitines and reductions in albumin and amino
      acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth
      hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected
      patients had higher triglycerides, ketones, and even-chain acylcarnitines and
      lower leptin and adiponectin levels than HIV-negative patients. Leptin levels
      rose in all patients following nutritional intervention, but adiponectin levels
      remained depressed in HIV-infected children. Baseline hypoleptinemia and
      hypoadiponectinemia were associated with increased mortality. CONCLUSIONS: Our
      findings suggest a critical interplay between HIV infection and adipose tissue
      storage and function in the adaptation to malnutrition. Hypoleptinemia and
      hypoadiponectinemia may contribute to high mortality rates among malnourished,
      HIV-infected children.

PMID- 25050736
TI  - Multiscale, hierarchically patterned topography for directing human neural stem
      cells into functional neurons.
AB  - Various biophysical and biochemical factors are important for determining the
      fate of neural stem cells (NSCs). Among biophysical signals, topographical
      stimulation by micro/nanopatterns has been applied to control NSC
      differentiation. In this study, we developed a hierarchically patterned substrate
      (HPS) platform that can synergistically enhance the differentiation of human NSCs
      (hNSCs) by simultaneously providing microscale and nanoscale spatial controls to
      facilitate the alignment of the cytoskeleton and the formation of focal
      adhesions. The multiscale HPS was fabricated by combining microgroove patterns
      (groove size: 1.5 MUm), prepared by a conventional photolithographic process, and
      nanopore patterns (pore diameter: 10 nm), prepared from cylinder-forming block
      copolymer thin films. The hNSCs grown on the HPS exhibited not only a highly
      aligned, elongated morphology, but also a greatly enhanced differentiation into
      neuronal and astrocyte lineages, compared to hNSCs on a flat substrate (FS) or
      single-type patterned substrates [microgroove patterned substrate (MPS) and
      nanopore patterned substrate (NPS)]. Interestingly, the application of the HPS
      directed hNSC differentiation toward neurons rather than astrocytes. The
      expression of focal adhesion proteins in hNSCs was also significantly increased
      on the HPS compared to the FS, MPS, and NPS, likely a result of the presence of
      more focal contact points provided by nanopore structures. Inhibition of both
      beta1 integrin-mediated binding and the intracellular Rho-associated protein
      kinase pathway of hNSCs eliminated the beneficial effects of the HPS on focal
      adhesion formation and actin filament alignment, which subsequently reduced hNSC
      differentiation. More importantly, hNSCs on the HPS differentiated into
      functional neurons exhibiting sodium currents and action potentials. The
      multiscale, hierarchically patterned topography would be useful for the design of
      functional biomaterial scaffolds to potentiate NSC therapeutic efficacy.

PMID- 25050737
TI  - Rottlerin suppresses growth of human pancreatic tumors in nude mice, and
      pancreatic cancer cells isolated from Kras(G12D) mice.
AB  - The purpose of the study was to examine the molecular mechanisms by which
      rottlerin inhibited growth of human pancreatic tumors in Balb C nude mice, and
      pancreatic cancer cells isolated from Kras(G12D) mice. AsPC-1 cells were injected
      subcutaneously into Balb c nude mice, and tumor-bearing mice were treated with
      rottlerin. Cell proliferation and apoptosis were measured by Ki67 and TUNEL
      staining, respectively. The expression of components of Akt, Notch, and Sonic
      Hedgehog (Shh) pathways were measured by the immunohistochemistry, Western blot
      analysis, and/or q-RT-PCR. The effects of rottlerin on pancreatic cancer cells
      isolated from Kras(G12D) mice were also examined. Rottlerin-treated mice showed a
      significant inhibition in tumor growth which was associated with suppression of
      cell proliferation, activation of capase-3 and cleavage of PARP. Rottlerin
      inhibited the expression of Bcl-2, cyclin D1, CDK2 and CDK6, and induced the
      expression of Bax in tumor tissues compared to untreated control. Rottlerin
      inhibited the markers of angiogenesis (Cox-2, VEGF, VEGFR, and IL-8), and
      metastasis (MMP-2 and MMP-9), thus blocking production of tumorigenic mediators
      in tumor microenvironment. Rottlerin also inhibited epithelial-mesenchymal
      transition by up-regulating E-cadherin and inhibiting the expression of Slug and
      Snail. Furthermore, rottlerin treatment of xenografted tumors or pancreatic
      cancer cells isolated from Kras(G12D) mice showed a significant inhibition in
      Akt, Shh and Notch pathways compared to control groups. These data suggest that
      rottlerin can inhibit pancreatic cancer growth by suppressing multiple signaling
      pathways which are constitutively active in pancreatic cancer. Taken together,
      our data show that the rottlerin induces apoptosis and inhibits pancreatic cancer
      growth by targeting Akt, Notch and Shh signaling pathways, and provide a new
      therapeutic approach with translational potential for humans. 

PMID- 25050739
TI  - Targeting cyclic hypoxia to prevent malignant progression and therapeutic
      resistance of cancers.
AB  - Emerging evidence shows that cyclic hypoxia exists in most solid cancers. It is
      believed that under cyclic hypoxic conditions cancer cells exhibit more malignant
      biological behaviors than under chronic hypoxic conditions. In this review, we
      provide a collection of evidence showing the molecular mechanisms by which cyclic
      hypoxia induces aggressiveness, malignant progression, and therapeutic resistance
      in cancers. Moreover, we propose that cyclic hypoxia is responsible for the
      regulation of cancer stem cells, which possess typical biological characteristics
      of therapeutic resistance. Based on the present findings, some key factors
      regulated by cyclic hypoxia may serve as potential targets for the prevention of
      malignant progression and the treatment of solid cancers. Much research is
      necessary to gain further insights into the biological aspects of cyclic hypoxia
      in the development and progression of cancers.

PMID- 25050740
TI  - Regio- and chemoselective intermolecular hydroamination of allyl imines for the
      synthesis of 1,2-diamines.
AB  - The synthesis of 1,2-diamines via a Rh-catalyzed intermolecular hydroamination of
      N-allyl imines with cyclic amines is presented. Coordinating groups proximal to
      the olefin bind to the catalyst and promote the transformation. The reaction
      affords 1,2-diamines in very good yields and is functional-group-tolerant and
      highly diastereoselective. 

PMID- 25050738
TI  - Antiproliferative activity of novel imidazopyridine derivatives on castration
      resistant human prostate cancer cells.
AB  - Metastatic prostate cancer (mPCa) relapses after a short period of androgen
      deprivation therapy and becomes the castration-resistant prostate cancer (CR
      PCa); to which the treatment is limited. Hence, it is imperative to identify
      novel therapeutic agents towards this patient population. In the present study,
      antiproliferative activities of novel imidazopyridines were compared. Among three
      derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory
      activity on LNCaP C-81 cell proliferation, following dose- and time-dependent
      manner. Additionally, AMD exhibited significant antiproliferative effect against
      a panel of PCa cells, but not normal prostate epithelial cells. Further, when
      compared to AMD, its derivative DME showed higher inhibitory activities on PCa
      cell proliferation, clonogenic potential and in vitro tumorigenicity. The
      inhibitory activity was apparently in part due to the induction of apoptosis.
      Mechanistic studies indicate that AMD and DME treatments inhibited both AR and
      PI3K/Akt signaling. The results suggest that better understanding of inhibitory
      mechanisms of AMD and DME could help design novel therapeutic agents for
      improving the treatment of CR PCa. 

PMID- 25050741
TI  - High glucose induces Rho/ROCK-dependent visfatin and type I procollagen
      expression in rat primary cardiac fibroblasts.
AB  - Myocardial fibrosis and excessive proliferation of cardiac fibroblasts (CFs)
      contribute to diabetic cardiomyopathy (DCM). However, the underlying mechanism is
      still not completely clear. The aim of this study was to investigate the
      relationship between high-glucose treatment and the expression of visfatin and
      type I procollagen in rat CFs, and examine the regulatory effects of high-glucose
      treatment on the Rho/ROCK signaling pathway. CFs from newborn Sprague Dawley rats
      were treated with high concentrations of glucose (10, 30 and 50 mmol/l D
      glucose), a baseline concentration of glucose (5.5 mmol/l) as a control, and
      mannitol (5.5 mmol/l D-glucose + 44.5 mmol/l mannitol) as an osmotic control. CFs
      were also treated with 30 mmol/l D-glucose for 6, 12, 24 and 48 h. The
      proliferation of CFs was determined by the MTT assay. The mRNA and protein
      expression of visfatin and type I procollagen were quantified by RT-qPCR and
      western blot analysis, respectively. Cardiac fibroblast proliferation reached a
      peak at 30 mmol/l D-glucose, and visfatin and type I procollagen expression were
      significantly increased upon treatment with high concentrations of glucose (10
      and 30 mmol/l) compared to baseline glucose treatment. Treatment with 30 mmol/l D
      glucose time-dependently promoted cardiac fibroblast proliferation. The mRNA and
      protein expression of visfatin and type I procollagen were significantly
      increased compared to the control at 24 h after 30 mmol/l D-glucose treatment.
      Y27632, a Rho-associated protein kinase (ROCK) inhibitor, significantly decreased
      the mRNA and protein levels of visfatin and type I procollagen, induced by 30
      mmol/l D-glucose (all P<0.05). In conclusion, a high level of glucose promotes
      cardiac fibroblast proliferation, and induces visfatin and type I procollagen
      expression in CFs, at least partially via the Rho/ROCK signaling pathway. These
      results may be helpful in developing an appropriate therapeutic strategy for DCM.

PMID- 25050742
TI  - Protein phosphatase 4 promotes hepatic lipogenesis through dephosphorylating
      acetyl-CoA carboxylase 1 on serine 79.
AB  - Reversible phosphorylation has a critical role in the regulation of the activity
      of acetyl-CoA carboxylase 1 (ACC1), which is associated with de novo lipogenesis.
      It has been shown that AMP-activated protein kinase (AMPK) phosphorylates ACC1 on
      serine 79 and inhibits its activity; however, the mechanism of ACC1
      dephosphorylation remains elusive. Protein phosphatase 4 (PP4), a ubiquitous
      serine/threonine phosphatase, regulates a variety of cellular functions; however,
      whether PP4 is involved in lipid metabolism has yet to be elucidated. In the
      present study, PP4 was identified as a novel regulator of ACC1, which is also
      involved in hepatic lipogenesis. The expression of PP4 was found to be
      significantly increased in the livers of db/db mice. Furthermore, pACC1
      Ser79/ACC1 levels were observed to be decreased and high triglyceride
      accumulation was found in the livers of db/db mice. Moreover, PP4 overexpression
      was observed to lead to a decreased pACC1-Ser79/ACC1 ratio and subsequently an
      increased intracellular triglyceride content in mouse primary hepatocytes. PP4
      was also found to directly interact with pACC1-Ser79 in human HepG2 cells. In
      conclusion, the present study showed that PP4 may be a novel regulator in hepatic
      lipogenesis through dephosphorylating ACC1 on serine 79, suggesting that PP4 may
      be a promising therapeutic target in lipid metabolism disorders. 

PMID- 25050744
TI  - Ternary hybrid systems of P3HT-CdSe-WS2 nanotubes for photovoltaic applications.
AB  - Hybrid heterojunctions of conjugated polymers and inorganic nanomaterials are a
      promising combination for obtaining high performance solar cells (SC). In this
      work we have explored new possible uses of the WS2 nanotubes (NTs) both as the
      only acceptor material blended with a polymer and in ternary systems mixed with a
      polymer and quantum dots (QDs). In particular we have spectroscopically
      investigated binary blends of poly(3-hexylthiophene) (P3HT) and WS2 NTs, P3HT and
      CdSe QDs, and ternary blends of P3HT, CdSe QDs and WS2 NTs. We report
      fluorescence quenching effects of the QD signal in the P3HT-CdSe-WS2 system with
      the increase of NT concentration. Static and time-resolved fluorescence studies
      reveal efficient resonant energy transfer from the QDs to the NTs upon
      photoexcitation. The evidence of energetic interaction between WS2 NTs and QDs
      opens new fields of application of WS2 NTs and holds very promising potential for
      improving charge transfer phenomena in the active layer of hybrid solar cells. 

PMID- 25050743
TI  - AP-2alpha downregulation by cigarette smoke condensate is counteracted by p53 in
      human lung cancer cells.
AB  - Cumulative findings have demonstrated that the dysregulation of tumor suppressor
      genes may be implicated in cigarette smoke-induced carcinogenesis. Activating
      enhancer-binding protein 2 (AP-2) is a eukaryotic transcriptional factor that
      plays a significant role in embryonic development and tumorigenesis. The
      vertebrate AP-2 family consists of AP-2alpha, AP-2beta, AP-2gamma, AP-2delta and
      AP-2epsilon. Previous studies have suggested that cigarette smoking disrupts AP-2
      regulation. In the present study, we investigated the effects of cigarette smoke
      condensate (CSC) on AP-2alpha expression in human lung cancer cell lines (NCI
      H1299, NCI-H446 and A549), as well as the potential mechanisms involved. Using RT
      qPCR, we found that CSC decreased AP-2alpha expression by suppressing its
      transcription in human lung cancer cell lines, particularly in p53-deficient NCI
      H1299 cells. Western blotting and luciferase assays were implemented and we found
      that the restoration of p53 expression rescued the NCI-H1299 cells from CSC
      induced AP-2alpha loss, while the silencing of p53 resulted in increased AP
      2alpha loss induced by CSC, suggesting an antagonizing role of p53 in the
      regulation of AP-2alpha by CSC. Our results indicate that AP-2alpha
      downregulation may be involved in smoke-induced lung carcinogenesis.

PMID- 25050745
TI  - Shell thickness-dependent microwave absorption of core-shell Fe3O4@C composites.
AB  - Core-shell composites, Fe3O4@C, with 500 nm Fe3O4 microspheres as cores have been
      successfully prepared through in situ polymerization of phenolic resin on the
      Fe3O4 surface and subsequent high-temperature carbonization. The thickness of
      carbon shell, from 20 to 70 nm, can be well controlled by modulating the weight
      ratio of resorcinol and Fe3O4 microspheres. Carbothermic reduction has not been
      triggered at present conditions, thus the crystalline phase and magnetic property
      of Fe3O4 micropsheres can be well preserved during the carbonization process.
      Although carbon shells display amorphous nature, Raman spectra reveal that the
      presence of Fe3O4 micropsheres can promote their graphitization degree to a
      certain extent. Coating Fe3O4 microspheres with carbon shells will not only
      increase the complex permittivity but also improve characteristic impedance,
      leading to multiple relaxation processes in these composites, thus the microwave
      absorption properties of these composites are greatly enhanced. Very
      interestingly, a critical thickness of carbon shells leads to an unusual
      dielectric behavior of the core-shell structure, which endows these composites
      with strong reflection loss, especially in the high frequency range. By
      considering good chemical homogeneity and microwave absorption, we believe the as
      fabricated Fe3O4@C composites can be promising candidates as highly effective
      microwave absorbers. 

PMID- 25050746
TI  - Gerdy's tubercle: the lighthouse to the knee.
AB  - OBJECTIVE: Identification of Gerdy's tubercle is the mainstay to any approach to
      the knee. Most surgical approaches to the proximal tibia and distal femur
      reference Gerdy's tubercle as a critical landmark. Its identification is
      therefore paramount. Unfortunately, the bony landmark can be skewed by soft
      tissue swelling, morbid obesity, or disruption from bony injury. The objective of
      this study was to determine a reliable way of identifying the normal anatomic
      location of Gerdy's tubercle using surrounding structures during any surgical
      approach to the knee. DESIGN: Anatomic cadaver study. SETTING: Academic
      laboratory center. MATERIALS AND METHODS: Twenty-four adult human cadaver lower
      extremities as 12 matched pairs were used. Systematic identification and
      measurement from the point of intersection of a line drawn between 2 corners of a
      box created using the tibial tubercle, inferior pole of the patella, and the
      fibula head were performed and recorded. MAIN OUTCOME MEASUREMENT: Mean distance
      from cutaneous point of intersection to Gerdy's tubercle upon dissection.
      RESULTS: The mean distance from the point of intersection to Gerdy's tubercle was
      2.58 +/- 2.01 mm with a range from 0 to 8. The mean distances for the right and
      left lower extremities were 2.67 +/- 2.02 and 2.5 +/- 2.11 mm, respectively.
      Statistical analysis using 2-tailed independent t test with a significance set at
      P <0.05 revealed no significant differences with P = 0.84. CONCLUSIONS: Our group
      has identified the point of intersection among 3 landmarks forming a point of
      intersection. This point is the intersection of a line drawn between 2 corners of
      a box created using the tibial tubercle, inferior pole of the patella, and the
      fibula head. This serves as a reliable and reproducible method to identify
      Gerdy's tubercle.

PMID- 25050747
TI  - Complications of high-energy bicondylar tibial plateau fractures treated with
      dual plating through 2 incisions.
AB  - OBJECTIVES: To characterize the rate of complications after operative fixation of
      bicondylar (OTA/AO 41-C) tibial plateau fractures and to evaluate the
      contribution of common risk factors. DESIGN: Retrospective review. SETTING: Level
      1 regional trauma center. PATIENTS/PARTICIPANTS: One hundred thirty-eight
      patients older than 18 years with 140 bicondylar tibial plateau fractures were
      participated in this study. INTERVENTION: Open reduction and internal fixation
      using medial and lateral plate construct through 2 incisions. MAIN OUTCOME
      MEASUREMENTS: Development of a deep infection or a nonunion. RESULTS: The overall
      major complication rate was 27.9%: 23.6% deep infection and 10.0% nonunion. Open
      fractures were associated with a higher rate of infection: 43.8% versus 21.0% for
      closed injuries (odds ratio = 2.96, P = 0.05). Fasciotomy closure before
      definitive fixation was associated with significantly fewer deep infections
      compared with internal fixation with open fasciotomy wounds: 11.8% versus 50.0%
      (odds ratio = 7.5, P = 0.05). The presence of compartment syndrome, tobacco use,
      diabetes, and timing of surgery had no statistically significant association on
      the rate of infection or nonunion. CONCLUSIONS: Nonunion and deep infections
      occur commonly after staged open reduction and internal fixation of high-energy
      tibial plateau fractures. Open fractures and open fasciotomy wounds at the time
      of internal fixation are associated with higher rates of infection. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25050748
TI  - Time to initial operative treatment following open fracture does not impact
      development of deep infection: a prospective cohort study of 736 subjects.
AB  - OBJECTIVES: To evaluate the association between time to surgery, antibiotic
      administration, Gustilo grade, fracture location, and development of deep
      infection in open fractures. DESIGN: Prospective cohort between 2001 and 2009.
      SETTING: Three Level 1 Canadian trauma centers. PARTICIPANTS: A total of 736 (791
      fractures) subjects were enrolled and 686 subjects (93%; 737 fractures) provided
      adequate follow-up data (1-year interview and/or clinical follow-up >90 days).
      INTERVENTION: Demographics, injury information, time to surgery, and antibiotics
      were recorded. Subjects were evaluated using standardized data forms until the
      fracture(s) healed. Phone interviews were undertaken 1 year after the fracture.
      MAIN OUTCOME MEASURES: Infection requiring unplanned surgical debridement and/or
      sustained antibiotic therapy. RESULTS: Tibia/fibula fractures were most common (n
      = 413, 52%), followed by upper extremity (UE) (n = 285, 36%), and femoral (n =
      93, 12%) fractures. Infection developed in 46 fractures (6%). The median time to
      surgery was 9 hours 4 minutes (interquartile range, 6 hours 39 minutes to 12
      hours 33 minutes) and 7 hours 39 minutes (interquartile range, 6 hours 10 minutes
      to 9 hours 54 minutes) for those without and with infection, respectively (P =
      0.04). Gustilo grade 3B/3C fractures accounted for 17 of 46 infections (37%) (P <
      0.001). Four UE (1.5%), 7 femoral (8%), and 35 tibia/fibula (9%) fractures
      developed infections (P = 0.001). Multivariate regression found no association
      between infection and time to surgery [odds ratio (OR), 0.97; 95% confidence
      interval (95% CI), 0.90-1.06] or antibiotics (OR, 1.0; 95% CI, 0.90-1.05). Grades
      3A (OR, 6.37; 95% CI, 1.37-29.56) and 3B/3C (OR, 12.87; 95% CI, 2.72-60.95)
      relative to grade 1 injuries and tibia/fibula (OR, 3.91; 95% CI, 1.33-11.53)
      relative to UE fractures were significantly associated with infection.
      CONCLUSION: Infection after open fracture was associated with increasing Gustilo
      grade or tibia/fibula fractures but not time to surgery or antibiotics. LEVEL OF
      EVIDENCE: Prognostic level I. See instructions for authors for a complete
      description of levels of evidence.

PMID- 25050749
TI  - Fix it or discard it? A retrospective analysis of functional outcomes after
      surgically treated patella fractures comparing ORIF with partial patellectomy.
AB  - OBJECTIVES: The goal of this study was to compare functional outcomes of patients
      with patella fractures treated with open reduction and internal fixation (ORIF)
      with those treated with partial patellectomy (PP). DESIGN: Retrospective cohort
      study. SETTING: Urban Level I Trauma Center. PATIENTS: Seventy-three patients
      with isolated displaced patella fractures underwent operative treatment between
      January 1, 2002, and December 31, 2009, at our institution. Of these, 52 (71%)
      patients with isolated patella fractures with minimum 1-year follow-up agreed to
      participate and were enrolled in the study. INTERVENTION: PP or ORIF. MAIN
      OUTCOME MEASUREMENTS: Patients completed outcome questionnaires and participated
      in a physical examination. Outcome instruments included the Knee Outcome Survey
      Activities of Daily Living Scale, Short Form (SF)-36 Health Survey, and SF
      Musculoskeletal Function Assessment Survey. RESULTS: Twenty-six patients
      underwent PP and 26 underwent ORIF. There were no significant differences in any
      of the functional outcome instruments, including Knee Outcome Survey-Activities
      of Daily Living Scale (ORIF: 64.1 +/- 11, PP: 62.1 +/- 7.9, P = 0.76), SF-36
      physical component score (ORIF: 40.8 +/- 5.4, PP: 41.1 +/- 5.2, P = 0.94), SF-36
      mental component (ORIF: 47.7 +/- 5.1, PP: 51.8 +/- 4.9, P = 0.19), Short
      Musculoskeletal Function Assessment (SMFA) Function Index (ORIF: 28.6 +/- 9.1,
      PP: 27.7 +/- 6.7, P = 0.78), or SMFA Bother Index (ORIF: 26.0 +/- 9.7, PP: 23.6
      +/- 8.8, P = 0.72). Complication rates did not differ significantly between the 2
      groups. CONCLUSIONS: This study demonstrates that functional impairment persists
      after operative treatment of patella fractures. Both ORIF and PP demonstrated
      similar final range of motion, functional scores, and complication rates. Despite
      its purported benefits, in this study, ORIF did not result in superior outcomes
      compared with PP. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 25050750
TI  - A prospective study of pain reduction and knee dysfunction comparing femoral
      skeletal traction and splinting in adult trauma patients.
AB  - OBJECTIVES: To determine if distal femoral traction pins result in knee
      dysfunction in patients with femoral or pelvic fracture, and to determine if
      skeletal traction relieves pain more effectively than splinting for femoral shaft
      fractures. DESIGN: Prospective cohort trial. SETTING: Level I urban trauma
      center. PATIENTS/PARTICIPANTS: One hundred twenty adult patients with femoral
      shaft, acetabular, and unstable pelvic fractures. INTERVENTION: Patients with
      femoral shaft fractures were placed into distal femoral skeletal traction or a
      long-leg splint, based on an attending-specific protocol. Patients with pelvic or
      acetabular fractures with instability or intraarticular bone fragments were
      placed into skeletal traction. MAIN OUTCOME MEASUREMENTS: An initial Lysholm knee
      survey was administered to assess preinjury knee pain and function; the survey
      was repeated at 3- and 6-month follow-up visits. Also, a 10-point visual analog
      scale was used to document pain immediately before, during, and immediately after
      fracture immobilization with traction or splinting. RESULTS: Thirty-five patients
      (29%) were immobilized with a long-leg splint, and 85 (71%) were immobilized with
      a distal femoral traction pin. Eighty-four patients (70%) completed a 6-month
      follow-up. Lysholm scores decreased by a mean 9.3 points from preinjury baseline
      to 6 months postinjury in the entire cohort (P < 0.01); no significant
      differences were found between the splint and traction pin groups. During
      application of immobilization, visual analog scale pain scores were significantly
      lower in traction patients as compared with splinted patients (mean, 1.9 points
      less, P < 0.01). Traction pins caused no infections, neurovascular injuries, or
      iatrogenic fractures. CONCLUSIONS: Distal femoral skeletal traction does not
      result in detectable knee dysfunction at 6 months after insertion, and results in
      less pain during and after immobilization than long-leg splinting. LEVEL OF
      EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25050751
TI  - Cadaveric investigation on radial nerve strain using different posterior surgical
      exposures for extraarticular distal humeral ORIF: merits of nerve decompression
      through a lateral paratricipital exposure.
AB  - OBJECTIVE: To determine whether the type of posterior surgical approach for
      distal humeral fracture open reduction and internal fixation influenced radial
      nerve strain during simulated operative retraction in a cadaveric model. METHODS:
      Three different posterior surgical exposures: triceps splitting, lateral
      paratricipital, and paratricipital with release of the lateral intermuscular
      septum were used. Radial nerve strain was measured using a microDVRT, while
      traction was applied with a digital force gauge at forces 0.1-0.3 kg. RESULTS:
      The lateral paratricipital with nerve decompression was superior to both the
      triceps splitting approach (P < 0.048) and paratricipital method without
      decompression (P < 0.036). There was no significant difference between the
      triceps splitting method and paratricipital exposure without intermuscular septum
      release. CONCLUSIONS: Radial nerve decompression through release of the lateral
      intermuscular septum through a lateral paratricipital exposure ideally decreases
      nerve strain during humeral open reduction and internal fixation in our cadaveric
      model.

PMID- 25050752
TI  - Complications after distal radius fracture surgery: results from a Swedish
      nationwide registry study.
AB  - OBJECTIVES: To evaluate complications after distal radius fracture surgery.
      DESIGN: Prospective registry study. SETTING: Nationwide registry study. PATIENTS:
      A total of 36,618 patients who underwent surgery because of a distal radius
      fracture during the period from January 1, 2001 to December 31, 2009 were
      followed from the date of operation until the occurrence of either reoperation, a
      new distal radius fracture, death, or December 31, 2010, whichever occurred
      first. MAIN OUTCOME MEASUREMENT: The occurrence of reoperations after different
      surgical methods is presented as proportions, incidence rates, and in a Kaplan
      Meier survival analysis curve. Types and distributions of complications are
      presented for pinning, external fixation (EF), and plating, respectively.
      RESULTS: The incidence of reoperation after fracture surgery using EF, pins, and
      plating was 100 [95% confidence interval (CI): 93-107], 140 (95% CI: 127-153),
      and 222 (95% CI: 207-237) per 10,000 person years, respectively. After stratified
      analysis adjusting for age and gender, the differences remained significant when
      comparing plating with EF (P = 0.001) and pinning (P = 0.01). Pinning and EF
      patients displayed an earlier onset of the complications when compared with
      plated patients. CONCLUSIONS: The incidence of reoperation was higher for
      patients treated with a plate than for patients treated with pins or EF. The
      timing of the reoperations differed in that pinning and EF patients displayed an
      earlier onset when compared with plated patients. LEVEL OF EVIDENCE: Prognostic
      Level II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25050753
TI  - Hexanuclear, heterometallic, Ni3Ln3 complexes possessing O-capped homo- and
      heterometallic structural subunits: SMM behavior of the dysprosium analogue.
AB  - The reaction of hetero donor chelating mannich base ligand 6,6'-{(2
      (dimethylamino)ethylazanediyl)bis(methylene)}bis(2-methoxy-4-methylphenol) with
      Ni(ClO4)2.6H2O and lanthanide(III) salts [Dy(III) (1); Tb(III) (2); Gd (III) (3);
      Ho(III) (4); and Er(III) (5)] in the presence of triethylamine and pivalic acid
      afforded a series of heterometallic hexanuclear Ni(II)-Ln(III) coordination
      compounds, [Ni3Ln3(MU3-O)(MU3-OH)3(L)3(MU
      OOCCMe3)3].(ClO4).wCH3CN.xCH2Cl2.yCH3OH.zH2O [for 1, w = 8, x = 3, y = 0, z =
      5.5; for 2, w = 0, x = 5, y = 0, z = 6.5; for 3, w = 15, x = 18, y = 3, z = 7.5;
      for 4, w = 15, x = 20, y = 6, z = 9.5; and for 5, w = 0, x = 3, y = 2, z = 3].
      The molecular structure of these complexes reveals the presence of a monocationic
      hexanuclear derivative containing one perchlorate counteranion. The asymmetric
      unit of each of the hexanuclear derivatives comprises the dinuclear motif
      [NiLn(L)(MU3-O)(MU3-OH)(MU-Piv)]. The cation contains three interlinked O-capped
      clusters: one Ln(III)3O and three Ni(II)Ln(III)2O. Each of the lanthanide centers
      is eight- coordinated (distorted trigonal-dodecahedron), while the nickel centers
      are hexacoordinate (distorted octahedral). The study of the magnetic properties
      of all compounds are reported and suggests single molecule magnet behavior for
      the Dy(III) derivative (1). 

PMID- 25050755
TI  - Four-muscle tenotomy surgery for nystagmus.
AB  - PURPOSE OF REVIEW: To describe the history and literature related to four-muscle
      tenotomy procedure for nystagmus. RECENT FINDINGS: The concept of four-muscle
      tenotomy surgery for nystagmus initially arose from objective eye movement
      recordings of patients with nystagmus and an eccentric face turn who had
      undergone the Anderson-Kestenbaum procedure. These eye movement recordings
      demonstrated secondary benefits, including broadening of the null region,
      improved visual acuity, and improved nystagmus waveforms. Studies initially
      performed in dogs validated the theory that such positive effects could be
      obtained by horizontal four-muscle tenotomy and reattachment without
      transposition. Subsequent studies in humans have demonstrated that the procedure
      results in improved visual acuity, broadening of the null zone, and improved
      target acquisition in patients with nystagmus. New theories have been described
      regarding techniques to augment the effects of the procedure and/or replicate its
      effects with a safer, less invasive alternative. SUMMARY: Horizontal four-muscle
      tenotomy has proven to be an effective procedure for reducing nystagmus,
      broadening the null position, and improving visual acuity in primary position for
      patients with nystagmus.

PMID- 25050756
TI  - Strabismus surgery for children with developmental delay.
AB  - PURPOSE OF REVIEW: To describe recent evidence regarding the surgical approach of
      strabismus in children with various forms of developmental delay. RECENT
      FINDINGS: There remains variability in surgical outcomes with or without dose
      adjustment in strabismus surgery for children with developmental delay. However,
      this should not deter one from performing surgery - even early surgery, as
      fusional potential remains possible, which can especially impact the quality of
      vision and quality of life in developmentally delayed children.Future
      prospective, comparative, long-term studies with larger sample sizes for
      strabismus surgery in children with developmental delay are still needed.
      SUMMARY: Strabismus is one of the most common ophthalmologic findings in children
      with developmental delay. Surgical correction of strabismus in children with
      developmental delay is well tolerated and effective, although it remains slightly
      less predictable, which can depend on the specific type of delay or underlying
      neurological deficit. Careful consideration of types and severity of
      developmental delay and attempts to measure binocular potential can help guide
      the timing, dosage, and type of treatment.Reoperations tend to be more frequently
      encountered in this population, and this higher degree of variability should be
      addressed in the consent process.Considering adjusting the surgical dosage in
      this population, taking careful preoperative measurements, and checking for
      fusional potential should be taken into account when managing children with
      developmental delay.

PMID- 25050754
TI  - Analysis of three-dimensional aerosol deposition in pharmacologically relevant
      terms: beyond black or white ROIs.
AB  - BACKGROUND: This article presents a novel methodological approach to evaluate
      images of aerosol deposition taken with PET-CT cameras. Traditionally, Black-or
      White (BW) Regions of Interest (ROIs) are created to cover Anatomical Regions
      (ARs) segmented from the high-resolution CT. Such ROIs do not usually consider
      blurring effects due to limited spatial resolution or breathing motion, and do
      not consider uncertainty in the AR position within the PET image. The new
      methodology presented here (Grayscale) addresses these issues, allows estimates
      of aerosol deposition within ARs, and expresses the deposition in terms of Tissue
      Dosing (in the lung periphery) and Inner Surface Concentration (in the larger
      airways). METHODS: Imaging data included a PET deposition image acquired during
      breathing and two CT scans acquired during breath holds at different lung
      volumes. The lungs were segmented into anatomically consistent ARs to allow
      unbiased comparisons across subjects and across lobes. The Grayscale method
      involves defining Voxel Influence Matrices (VIMs) to consider how average
      activity within each AR influences the measured activity within each voxel. The
      BW and Grayscale methods were used to analyze aerosol deposition in 14
      bronchoconstricted asthmatics. RESULTS: Grayscale resulted in a closer
      description of the PET image than BW (p<0.0001) and exposed a seven-fold
      underestimation in measures of specific deposition. The Average Tissue Dosing was
      2.11*10(-6) Total Lung Dose/mg. The average Inner Surface Concentration was
      45*10(-6) Total Lung Dose/mm(2), with the left lower lobe having a lower ISC than
      lobes of the right lung (p<0.05). There was a strong lobar heterogeneity in these
      measures (COV=0.3). CONCLUSION: The Grayscale approach is an improvement over the
      BW approach and provides a closer description of the PET image. It can be used to
      characterize heterogeneous concentrations throughout the lung and may be
      important in translational research and in the evaluation of aerosol delivery
      systems.

PMID- 25050757
TI  - Surgical preferences for lateral canthoplasty and canthopexy.
AB  - PURPOSE OF REVIEW: To describe the currently used techniques of lateral canthal
      tightening and their indications. RECENT FINDINGS: The treatment of involutional
      ectropion involves horizontal tightening of the lower eyelid via a lateral
      canthal resuspension procedure, which can be either a canthopexy or a
      canthoplasty. The lateral tarsal strip, one of the most common canthoplasty
      procedures performed today, is a powerful technique, very useful in cases of
      profound eyelid laxity or ectropion in which horizontal eyelid shortening is
      necessary to achieve adequate eyelid tightening.For less-severe eyelid laxity, a
      canthopexy can be performed through either an upper or a lower eyelid incision,
      in which the suture is passed through the eyelid incision without externalization
      at the lateral canthal angle. We recently described the lateral canthal
      resuspension sine canthotomy technique that was slightly more effective than the
      lateral tarsal strip at decreasing the MRD-2 and lengthened the horizontal
      palpebral aperture without significantly changing the lateral canthal height.
      SUMMARY: Although the lateral canthal resuspension sine canthotomy technique has
      advantages for tightening loose lower eyelids in both cosmetic and functional
      cases, the lateral tarsal strip remains the procedure of choice for severe lid
      laxity or ectropion.

PMID- 25050758
TI  - Magnetic force microscopy: quantitative issues in biomaterials.
AB  - Magnetic force microscopy (MFM) is an atomic force microscopy (AFM) based
      technique in which an AFM tip with a magnetic coating is used to probe local
      magnetic fields with the typical AFM spatial resolution, thus allowing one to
      acquire images reflecting the local magnetic properties of the samples at the
      nanoscale. Being a well established tool for the characterization of magnetic
      recording media, superconductors and magnetic nanomaterials, MFM is finding
      constantly increasing application in the study of magnetic properties of
      materials and systems of biological and biomedical interest. After reviewing
      these latter applications, three case studies are presented in which MFM is used
      to characterize: (i) magnetoferritin synthesized using apoferritin as molecular
      reactor; (ii) magnetic nanoparticles loaded niosomes to be used as nanocarriers
      for drug delivery; (iii) leukemic cells labeled using folic acid-coated core
      shell superparamagnetic nanoparticles in order to exploit the presence of folate
      receptors on the cell membrane surface. In these examples, MFM data are
      quantitatively analyzed evidencing the limits of the simple analytical models
      currently used. Provided that suitable models are used to simulate the MFM
      response, MFM can be used to evaluate the magnetic momentum of the core of
      magnetoferritin, the iron entrapment efficiency in single vesicles, or the uptake
      of magnetic nanoparticles into cells. 

PMID- 25050759
TI  - Far from resolved: stromal cell-based iTRAQ research of muscle-invasive bladder
      cancer regarding heterogeneity.
AB  - The aim of the present study was to globally characterize the cancer stroma
      expression profile of muscle-invasive bladder cancer in different metastatic risk
      groups and to discuss the decisive role of biological pathway change in cancer
      heterogeneity. Laser capture microdissection was employed to harvest purified
      muscle-invasive bladder cancer stromal cells derived from 30 clinical samples
      deriving from 3 different metastatic risk groups. Isobaric tags for relative and
      absolute quantitation (iTRAQ) and two-dimensional liquid chromatography tandem
      mass spectrometry (2D LC-MS/MS) were used to identify the differentially
      expressed proteins. Subsequently, the differentially expressed proteins were
      further analyzed by bioinformatics tools. After completing the above tasks, the
      proteins of interest were further compared with the published litterature. We
      identified 1,049 differentially expressed proteins by paired comparison (high
      risk vs. median, low risk and normal groups; median risk vs. low risk and normal
      groups, low risk vs. normal group; a total of 6 comparisons). A total of
      510,549,548 proteins as significantly altered (ratio fold-change>=1.5 or <=0.667
      between the metastatic potential risk group and the normal group) were presented
      in the low/median/high metastatic risk group, respectively. Pathway analysis
      revealed that the differentially expressed proteins were mainly located in the
      Kyoto Encyclopedia of Genes and Genomes pathways, including focal adhesion
      pathway, systemic lupus erythematosus pathway and ECM-receptor interaction
      pathway. In addition, several proteins such as EXOC4, MYH10 and MMP-9 may serve
      as candidate biomarkers of muscle-invasive bladder cancer. Our study confirmed
      that stromal cells, an important part of the cancer tissue, are pivotal for
      regulating the heterogeneity of cancer. Common changes in biological pathways
      determined the malignant phenotype of muscle-invasive bladder cancer, and
      biomarker discovery should take into account both neoplastic cells and their
      corresponding stromata.

PMID- 25050760
TI  - Evidence of hepatitis A virus person-to-person transmission in household
      outbreaks.
AB  - The person-to-person transmission of the hepatitis A virus primarily occurs in
      enclosed spaces, particularly in the presence of inadequate hygiene conditions
      and a high proportion of susceptible individuals. Thus, intimate family contact
      stands out as a risk factor for HAV infection dissemination. The present study
      aimed to evaluate the occurrence of household HAV transmission. Blood samples
      were collected from patients with hepatitis A (index cases) and their family
      members (contacts) that were referred to an ambulatory care clinic specializing
      in viral hepatitis. A total of 97 samples were collected from 30 families with a
      confirmed hepatitis A case (index case). Serological and molecular techniques for
      the diagnosis of hepatitis A were conducted on all samples. HAV infection (anti
      HAV IgM + and/or HAV RNA +) was detected in 34.3% (23/67) of the contacts; 34.3%
      (23/67) of the contacts were immune to HAV, and 31.4% (21/67) were susceptible.
      In the household contacts, HAV immunity was significantly associated with older
      age; susceptibility to infection and HAV infection were associated with younger
      age. Household outbreaks were detected in 16/30 families studied. Co-circulation
      of subgenotypes IA and IB was found in the household outbreaks, and person-to
      person transmission was evidenced in six of the household outbreaks, with 100%
      homology between the index case and contact strains. The results demonstrated the
      relevance of HAV household transmission, reaffirming the need for hepatitis A
      vaccine administration in susceptible contacts and effective infection control
      procedures to prevent the extension of household outbreaks. 

PMID- 25050762
TI  - Noninvasive prenatal testing for microdeletion syndromes and expanded trisomies:
      proceed with caution.

PMID- 25050761
TI  - Iron-rich ferritin in the hypoxia-tolerant rodent Spalax ehrenbergi: a naturally
      occurring biomarker confirms the internalization and pathways of intracellular
      macromolecules.
AB  - The discovery of pits/caveolae in the plasmalemma advanced the study of
      macromolecule internalization. "Transcytosis" describes the transport of
      macromolecular cargo from one front of a polarized cell to the other within
      membrane-bounded carrier(s), via endocytosis, intracellular trafficking and
      exocytosis. Clathrin-mediated transcytosis is used extensively by epithelial
      cells, while caveolae-mediated transcytosis mostly occurs in endothelial cells.
      The internalization pathways were monitored by various markers, including
      radioisotopes, nanoparticles, enzymes, immunostains, and fluorophores. We
      describe an internalization pathway identified using a naturally-occurring
      biomarker, in vivo assembled ferritin, containing electron-dense iron cores.
      Iron, an essential trace metal for most living species and iron homeostasis, is
      crucial for cellular life. Ferritin is a ubiquitous and highly conserved
      archeoprotein whose main function is to store a reserve iron supply inside the
      cytoplasm in a non-toxic form. Ferritin is present in all organisms which have a
      metabolic requirement for iron and in even in organisms whose taxonomic rank is
      very low. The newborns of the blind mole, Spalax ehrenbergi, are born and live in
      a hypoxic environment and have significant iron overload in their liver and
      heart, but their iron metabolism has not been previously studied. These newborns,
      which are evolutionarily adapted to fluctuations in the environmental oxygen,
      have a unique ability to sequester transplacental iron and store it in ferritin
      without any signs of iron toxicity. Using the ferrihydrite cores of ferritin, we
      were able to monitor the ferritin internalization from portals of its entry into
      the cytosol of hepatocytes and cardiomyocytes and into the lysosomes. 

PMID- 25050763
TI  - In reply.

PMID- 25050764
TI  - A practical approach to fetal growth restriction.

PMID- 25050765
TI  - In reply.

PMID- 25050770
TI  - Practice bulletin no. 146: Management of late-term and postterm pregnancies.
AB  - Postterm pregnancy refers to a pregnancy that has reached or extended beyond 42
      0/7 weeks of gestation from the last menstrual period (LMP), whereas a late-term
      pregnancy is defined as one that has reached between 41 0/7 weeks and 41 6/7
      weeks of gestation (). In 2011, the overall incidence of postterm pregnancy in
      the United States was 5.5% (). The incidence of postterm pregnancies may vary by
      population, in part as a result of differences in regional management practices
      for pregnancies that go beyond the estimated date of delivery. Accurate
      determination of gestational age is essential to accurate diagnosis and
      appropriate management of late-term and postterm pregnancies. Antepartum fetal
      surveillance and induction of labor have been evaluated as strategies to decrease
      the risks of perinatal morbidity and mortality associated with late-term and
      postterm pregnancies. The purpose of this document is to review the current
      understanding of late-term and postterm pregnancies and provide guidelines for
      management that have been validated by appropriately conducted outcome-based
      research when available. Additional guidelines on the basis of consensus and
      expert opinion also are presented. 

PMID- 25050771
TI  - Committee opinion no. 606: Options for prevention and management of heavy
      menstrual bleeding in adolescent patients undergoing cancer treatment.
AB  - Adolescents undergoing cancer treatment are at high risk of heavy menstrual
      bleeding, and gynecologists may be consulted either before the initiation of
      cancer treatment to request strategies for menstrual suppression or during an
      episode of severe heavy bleeding to stop the bleeding emergently. Therapy in both
      situations should be tailored to the patient, her cancer diagnosis and treatment
      plan, and her desires for contraception and fertility. Options for menstrual
      suppression include combined hormonal contraceptives, progestin-only therapy, and
      gonadotropin-releasing hormone agonists. Adolescents presenting emergently with
      severe uterine bleeding may benefit from hormonal therapy, antifibrinolytics or,
      as a last resort, surgical management. In choosing appropriate treatment,
      considerations such as current platelet count, course of treatment, time to
      expected nadir, risk of thromboembolism, and need for contraception should be
      considered. Because of the complex nature of cancer care, collaboration with the
      adolescent's oncologist is highly recommended.

PMID- 25050772
TI  - Committee opinion no. 607: Gynecologic concerns in children and adolescents with
      cancer.
AB  - Advancements in radiation therapy, chemotherapy, surgery, and multimodal
      treatment have dramatically improved childhood cancer survival. However, cancer
      and its treatment may have immediate or delayed adverse effects on reproductive
      health. Gynecologists should be prepared to manage gynecologic concerns in young
      cancer patients and survivors before, during, and after their treatment.
      Gynecologists may be consulted regarding pubertal concerns; heavy menstrual
      bleeding and anemia; sexuality; contraception; ovarian function, including
      fertility preservation; and breast and cervical cancer screening. The science of
      fertility preservation is a rapidly evolving field; therefore, a referral to a
      reproductive endocrinologist is recommended to explore the full range of
      available options.

PMID- 25050773
TI  - Vertebroplasty using bisphosphonate-loaded calcium phosphate cement in a
      standardized vertebral body bone defect in an osteoporotic sheep model.
AB  - In the context of bone regeneration in an osteoporotic environment, the present
      study describes the development of an approach based on the use of calcium
      phosphate (CaP) bone substitutes that can promote new bone formation and locally
      deliver in situ bisphosphonate (BP) directly at the implantation site. The
      formulation of a CaP material has been optimized by designing an injectable
      apatitic cement that (i) hardens in situ despite the presence of BP and (ii)
      provides immediate mechanical properties adapted to clinical applications in an
      osteoporotic environment. We developed a large animal model for simulating lumbar
      vertebroplasty through a two-level lateral corpectomy on L3 and L4 vertebrae
      presenting a standardized osteopenic bone defect that was filled with cements.
      Both 2-D and 3-D analysis of microarchitectural parameters demonstrated that
      implantation of BP-loaded cement in such vertebral defects positively influenced
      the microarchitecture of the adjacent trabecular bone. This biological effect was
      dependent on the distance from the implant, emphasizing the in situ effect of the
      BP and its release from the cement. As a drug device combination, this BP
      containing apatitic cement shows good promise as a local approach for the
      prevention of osteoporotic vertebral fractures through percutaneous
      vertebroplasty procedures. 

PMID- 25050774
TI  - Genetically modified Tomato aspermy virus 2b protein as a tumor-targeting siRNA
      delivery carrier.
AB  - In nature, there exist a wide range of dsRNA-binding proteins that have different
      binding modes for small interfering RNA (siRNA) as well as structural
      differences, and some of these proteins have potential as effective siRNA
      delivery carriers. In order to deliver siRNA into cancer cells, a dsRNA-binding
      2b protein derived from Tomato aspermy virus was genetically modified by fusing
      the integrin-targeting RGD peptide to its C-terminus, and biosynthesized. The
      resulting 2b-RGD protein possesses distinct characteristics favorable for
      biomedical applications of siRNA: (i) high affinity for siRNA, (ii) siRNA
      protection against RNases in serum, (iii) low cytotoxicity compared to the
      polycationic polymers often employed in conventional siRNA carriers, (iv)
      specific binding to integrins on cancer cells, and the ability to pass through
      the cell membrane via endocytosis, and (v) the ability to facilitate cytosolic
      release of siRNA. Here, we demonstrate that the 2b-RGD/siRNA complexes have great
      potential as a tumor-targeting siRNA delivery carrier and suggest their possible
      therapeutic applications for cancer treatment. 

PMID- 25050775
TI  - Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro
      and in vivo evaluation.
AB  - Nanoparticles (NP) that target bone tissue were developed using PLGA-PEG
      (poly(lactic-co-glycolic acid)-polyethylene glycol) diblock copolymers and bone
      targeting moieties based on aspartic acid, (Asp)(n(1,3)). These NP are expected
      to enable the transport of hydrophobic drugs. The molecular structures were
      examined by (1)H NMR or identified using mass spectrometry and Fourier transform
      infrared (FT-IR) spectra. The NP were prepared using the water miscible solvent
      displacement method, and their size characteristics were evaluated using
      transmission electron microscopy (TEM) and dynamic light scattering. The bone
      targeting potential of the NP was evaluated in vitro using hydroxyapatite
      affinity assays and in vivo using fluorescent imaging in zebrafish and rats. It
      was confirmed that the average particle size of the NP was <200 nm and that the
      dendritic Asp3 moiety of the PLGA-PEG-Asp3 NP exhibited the best apatite mineral
      binding ability. Preliminary findings in vivo bone affinity assays in zebrafish
      and rats indicated that the PLGA-PEG-ASP3 NP may display increased bone-targeting
      efficiency compared with other PLGA-PEG-based NP that lack a dendritic Asp3
      moiety. These NP may act as a delivery system for hydrophobic drugs, warranting
      further evaluation of the treatment of bone disease.

PMID- 25050776
TI  - Design and synthesis of potent macrocyclic HIV-1 protease inhibitors involving P1
      P2 ligands.
AB  - A series of potent macrocyclic HIV-1 protease inhibitors have been designed and
      synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings
      between a nelfinavir-like P2 ligand and a tyrosine side chain containing a
      hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent
      than their corresponding acyclic counterparts. Saturated derivatives showed
      slight reduction of potency compared to the respective unsaturated derivatives.
      Compound containing a 16-membered ring as the P1-P2 ligand showed the most potent
      enzyme inhibitory and antiviral activity. 

PMID- 25050777
TI  - Expression of neuropeptide Y1 receptors in the amygdala and hippocampus and
      anxiety-like behavior associated with Ammon's horn sclerosis following
      intrahippocampal kainate injection in C57BL/6J mice.
AB  - Damage to the amygdala is often linked to Ammon's horn sclerosis (AHS) in
      surgical specimens of patients suffering from temporal lobe epilepsy (TLE).
      Moreover, amygdalar pathology is thought to contribute to the development of
      anxiety symptoms frequently found in TLE. The neuropeptide Y (NPY) Y1 receptor is
      critical in the regulation of anxiety-related behavior and epileptiform activity
      in TLE. Therefore, intrahippocampal kainate (KA) injection was performed to
      induce AHS-associated TLE and to investigate behavioral and cytoarchitectural
      changes that occur in the amygdala related to Y1 receptor expression. Status
      epilepticus was induced by intrahippocampal KA injection in C57BL/6J mice.
      Anxiety-like behavior was assessed using the elevated plus maze (EPM). Pathology
      of hippocampus and amygdala (volume loss and gliosis) was examined in KA-injected
      and saline-injected controls. Y1 receptor expression was measured using
      immunohistochemistry and ELISA. Animal injected with KA showed increased anxiety
      like behaviors and reduced risk assessment in the EPM test compared with saline
      injected controls. In the ipsilateral hippocampus of KA-injected animals, CA1
      ablation, granule cell dispersion, and volume reduction were accompanied by
      astrogliosis indicating the development of AHS. In the amygdala, a significant
      decrease in the volume of nuclei and numbers of neurons was observed in the
      ipsilateral lateral, basolateral, and central amygdalar nuclei, which was
      accompanied by astrogliosis. In addition, a decrease in Y1 receptor-expressing
      cells in the ipsilateral CA1 and CA3 sectors of the hippocampus, ipsilateral and
      contralateral granule cell layer of the dentate gyrus, and ipsilateral central
      nucleus of the amygdala was found, consistent with a reduction in Y1 receptor
      protein levels. Our results suggest that plastic changes in hippocampal and/or
      amygdalar Y1 receptor expression may negatively impact anxiety levels. Moreover,
      intrahippocampal KA injection can induce amygdalar damage suggesting that AHS
      associated amygdala damage may contribute to behavioral alterations seen in
      patients with TLE. 

PMID- 25050778
TI  - Zoning in on parents' needs: understanding parents' perspectives in order to
      provide person-centered care.
AB  - PURPOSE: In order to develop a theoretical framework for person-centered care
      models for children with epilepsy and their parents, we conducted a qualitative
      study to explore and understand parents' needs, values, and preferences to
      ultimately reduce barriers that may be impeding parents from accessing and
      obtaining help for their children's co-occurring problems. METHODS: A qualitative
      grounded theory study design was utilized to understand parents' perspectives.
      The participants were 22 parents of children with epilepsy whose age ranged from
      31 to 53 years. Interviews were conducted using open-ended semistructured
      questions to facilitate conversation. Transcripts were analyzed using grounded
      theory guidelines. RESULTS: In order to understand the different perspectives
      parents had about their child, we devised a theory composed of three zones (Zones
      1, 2, and 3) that can be used to conceptualize parents' viewpoints. Zone location
      was based on a parent's perspectives on their child's comorbidities in the
      context of epilepsy. These zones were developed to help identify distinctions
      between parents' perspectives and to provide a framework within which to
      understand parents' readiness to access and implement interventions to address
      the child's struggles. These zones of understanding describe a parent's
      perspectives on their children's struggles at a particular point in time. This is
      the perspective from which parents address their child's needs. This theoretical
      perspective provides a structure in which to discuss a parent's perspectives on
      conceptualizing or comprehending the child's struggles in the context of
      epilepsy. The zones are based on how the parents describe (a) their concerns
      about the child's struggles and (b) their understanding of the struggles and (c)
      the parent's view of the child's future. CONCLUSIONS: Clinicians working with
      individuals and families with epilepsy are aware that epilepsy is a complex and
      unpredictable disorder. The zones help clinicians conceptualize and build a
      framework within which to understand how parents view their child's struggles,
      which influences the parents' ability to understand and act on clinician feedback
      and recommendations. Zones allow for increased understanding of the parent at a
      particular time and provide a structure within which a clinician can provide
      guidance and feedback to meet parents' needs, values, and preferences. This
      theory allows clinicians to meet the parents where they are and address their
      needs in a way that benefits the parents, family, and child.

PMID- 25050780
TI  - Coexpression and secretion of endoglucanase and phytase genes in Lactobacillus
      reuteri.
AB  - A multifunctional transgenic Lactobacillus with probiotic characteristics and an
      ability to degrade beta-glucan and phytic acid (phytate) was engineered to
      improve nutrient utilization, increase production performance and decrease
      digestive diseases in broiler chickens. The Bacillus subtilis WL001 endoglucanase
      gene (celW) and Aspergillus fumigatus WL002 phytase gene (phyW) mature peptide
      (phyWM) were cloned into an expression vector with the lactate dehydrogenase
      promoter of Lactobacillus casei and the secretion signal peptide of the
      Lactococcus lactis usp45 gene. This construct was then transformed into
      Lactobacillus reuteri XC1 that had been isolated from the gastrointestinal tract
      of broilers. Heterologous enzyme production and feed effectiveness of this
      genetically modified L. reuteri strain were investigated and evaluated. Sodium
      dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that the
      molecular mass of phyWM and celW was approximately 48.2 and 55 kDa, respectively,
      consistent with their predicted molecular weights. Endoglucanase and phytase
      activities in the extracellular fraction of the transformed L. reuteri culture
      were 0.68 and 0.42 U/mL, respectively. Transformed L. reuteri improved the feed
      conversion ratio of broilers from 21 to 42 days of age and over the whole feeding
      period. However, there was no effect on body weight gain and feed intake of
      chicks. Transformed L. reuteri supplementation improved levels of ash, calcium
      and phosphorus in tibiae at day 21 and of phosphorus at day 42. In addition,
      populations of Escherichia coli, Veillonella spp. and Bacteroides vulgatus were
      decreased, while populations of Bifidobacterium genus and Lactobacillus spp. were
      increased in the cecum at day 21. 

PMID- 25050781
TI  - 4-hydroxyphenylacetic acid attenuated inflammation and edema via suppressing HIF
      1alpha in seawater aspiration-induced lung injury in rats.
AB  - 4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster
      tataricus which had been widely used in China for the treatment of pulmonary
      diseases. The aim of this study is to investigate the effect of 4-HPA on seawater
      aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by
      enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF)
      white cell count, Evans blue dye analysis, wet to dry weight ratios, and
      histology study. Hypoxia-inducible factor-1alpha (HIF-1alpha) siRNA and
      permeability assay were used to study the effect of 4-HPA on the production of
      inflammatory cytokines and monolayer permeability in vitro. The results showed
      that 4-HPA reduced seawater instillation-induced mortality in rats. In lung
      tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and
      decreased HIF-1alpha protein level. In primary rat alveolar epithelial cells
      (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1alpha protein
      levels through inhibiting the activations of protein translational regulators and
      via promoting HIF-1alpha protein degradation. In addition, 4-HPA lowered
      inflammatory cytokines levels through suppressing hypertonicity- and hypoxia
      induced HIF-1alpha in NR8383 macrophages. Moreover, 4-HPA decreased monolayer
      permeability through suppressing hypertonicity and hypoxia-induced HIF-1alpha,
      which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat
      lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA
      attenuated inflammation and edema through suppressing hypertonic and hypoxic
      induction of HIF-1alpha in seawater aspiration-induced lung injury in rats. 

PMID- 25050779
TI  - Modified low density lipoprotein and lipoprotein-containing circulating immune
      complexes as diagnostic and prognostic biomarkers of atherosclerosis and type 1
      diabetes macrovascular disease.
AB  - In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to
      multiple enzymatic and non-enzymatic modifications that increase their
      atherogenicity and induce immunogenicity. Modified LDL are capable of inducing
      vascular inflammation through activation of innate immunity; thus, contributing
      to the progression of atherogenesis. The immunogenicity of modified LDL results
      in induction of self-antibodies specific to a certain type of modified LDL. The
      antibodies react with modified LDL forming circulating immune complexes.
      Circulating immune complexes exhibit prominent immunomodulatory properties that
      influence atherosclerotic inflammation. Compared to freely circulating modified
      LDL; modified LDL associated with the immune complexes have a more robust
      atherogenic and proinflammatory potential. Various lipid components of the immune
      complexes may serve not only as diagnostic but also as essential predictive
      markers of cardiovascular events in atherosclerosis. Accumulating evidence
      indicates that LDL-containing immune complexes can also serve as biomarker for
      macrovascular disease in type 1 diabetes. 

PMID- 25050782
TI  - Effects of beta2-adrenergic receptor gene polymorphisms on ritodrine therapy in
      pregnant women with preterm labor: prospective follow-up study.
AB  - This study aimed to evaluate the effects of beta2-adrenergic receptor (ADRB2)
      gene polymorphisms on ritodrine therapy outcomes in patients with preterm labor.
      Genotyping analysis of ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718,
      and rs1042719) was performed on 137 patients with preterm labor. Survival
      analysis was conducted for the effects of SNPs on the median time to delivery as
      a primary outcome. The median time to delivery in the study patients was 349.3 h.
      Gestational age at admission and modified Bishop scores revealed significant
      effects on time to delivery (p<0.001). Among studied SNPs, rs1042717 and
      rs1042718 showed linkage disequilibrium in this population, and their effects on
      time to delivery were marginally significant (p<0.1). Patients with variant
      homozygotes in the rs1042713 showed considerably shortened time to delivery
      compared to wild-allele carriers. The rs1042719 polymorphism significantly
      affected time to delivery in both univariate and multivariate analysis; the GC
      and CC carriers showed 64% decrease in time to delivery compared to the wild-type
      homozygote carriers. Based on the results, it was concluded that the gene
      polymorphisms of ADRB2 could affect ritodrine therapy in patients with preterm
      labor. However, given the single-center and the relatively small sample size, our
      hypothesis requires further independent validation using multi-center and large
      sample size.

PMID- 25050784
TI  - Rapid adsorption of heavy metals by Fe3O4/talc nanocomposite and optimization
      study using response surface methodology.
AB  - Fe3O4/talc nanocomposite was used for removal of Cu(II), Ni(II), and Pb(II) ions
      from aqueous solutions. Experiments were designed by response surface methodology
      (RSM) and a quadratic model was used to predict the variables. The adsorption
      parameters such as adsorbent dosage, removal time, and initial ion concentration
      were used as the independent variables and their effects on heavy metal ion
      removal were investigated. Analysis of variance was incorporated to judge the
      adequacy of the models. Optimal conditions with initial heavy metal ion
      concentration of 100, 92 and 270 mg/L, 120 s of removal time and 0.12 g of
      adsorbent amount resulted in 72.15%, 50.23%, and 91.35% removal efficiency for
      Cu(II), Ni(II), and Pb(II), respectively. The predictions of the model were in
      good agreement with experimental results and the Fe3O4/talc nanocomposite was
      successfully used to remove heavy metals from aqueous solutions. 

PMID- 25050786
TI  - Mechanistic insights on cooperative asymmetric multicatalysis using chiral
      counterions.
AB  - Cooperative multicatalytic methods are steadily gaining popularity in asymmetric
      catalysis. The use of chiral Bronsted acids such as phosphoric acids in
      conjunction with a range of transition metals has been proven to be effective in
      asymmetric synthesis. However, the lack of molecular-level understanding and the
      accompanying ambiguity on the role of the chiral species in stereoinduction
      continues to remain an unresolved puzzle. Herein, we intend to disclose some
      novel transition state models obtained through DFT(B3LYP and M06) computations
      for a quintessential reaction in this family, namely, palladium-catalyzed
      asymmetric Tsuji-Trost allylation of aldehydes. The aldehyde is activated as an
      enamine by the action of a secondary amine (organocatalysis), which then adds to
      an activated Pd-allylic species (transition metal catalysis) generated through
      the protonation of allyic alcohol by chiral BINOL-phosphoric acid (Bronsted acid
      catalysis). We aim to decipher the nature of chiral BINOL-phosphates and their
      role in creating a quaternary chiral carbon atom in this triple catalytic system.
      The study reports the first transition state model capable of rationalizing
      chiral counterion-induced enantioselectivity. It is found that the chiral
      phosphate acts as a counterion in the stereocontrolling event rather than the
      conventional ligand mode. 

PMID- 25050783
TI  - Iodine excess as an environmental risk factor for autoimmune thyroid disease.
AB  - The global effort to prevent iodine deficiency disorders through iodine
      supplementation, such as universal salt iodization, has achieved impressive
      progress during the last few decades. However, iodine excess, due to extensive
      environmental iodine exposure in addition to poor monitoring, is currently a more
      frequent occurrence than iodine deficiency. Iodine excess is a precipitating
      environmental factor in the development of autoimmune thyroid disease. Excessive
      amounts of iodide have been linked to the development of autoimmune thyroiditis
      in humans and animals, while intrathyroidal depletion of iodine prevents disease
      in animal strains susceptible to severe thyroiditis. Although the mechanisms by
      which iodide induces thyroiditis are still unclear, several mechanisms have been
      proposed: (1) excess iodine induces the production of cytokines and chemokines
      that can recruit immunocompetent cells to the thyroid; (2) processing excess
      iodine in thyroid epithelial cells may result in elevated levels of oxidative
      stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3)
      iodine incorporation in the protein chain of thyroglobulin may augment the
      antigenicity of this molecule. This review will summarize the current knowledge
      regarding excess iodide as an environmental toxicant and relate it to the
      development of autoimmune thyroid disease. 

PMID- 25050785
TI  - WNT16B from ovarian fibroblasts induces differentiation of regulatory T cells
      through beta-catenin signal in dendritic cells.
AB  - Treatment for cancer can induce a series of secreted factors into the tumor
      microenvironment, which can affect cancer progression. Wingless-type MMTV (mouse
      mammary tumor virus) integration site 16B (WNT16B) is a new member of the WNT
      family and has been reported to play growth-related roles in previous studies. In
      this study, we found WNT16B could be expressed and secreted into the
      microenvironment by human ovarian fibroblasts after DNA damage-associated
      treatment, including chemotherapy drugs and radiation. We also demonstrated that
      fibroblast-derived WNT16B could result in accumulation of beta-catenin in
      dendritic cells and secretion of interleukin-10 (IL-10) and transforming growth
      factor beta (TGF-beta), which contributed to the differentiation of regulatory T
      cells in a co-culture environment. These results shed light on the roles of
      WNT16B in immune regulation, especially in regard to cancer treatment. 

PMID- 25050787
TI  - Phytochemical analysis and bioactivity of the aerial parts of Abutilon
      theophrasti (Malvaceae), a medicinal weed.
AB  - Phytochemical investigations of aerial parts of Abutilon theophrasti yielded
      (6S,9R)-roseoside (1) and (6S,9S)-roseoside (2) which are new for the genus. The
      elucidation of the chemical structures was established by mass spectrometry, 1D
      and 2D NMR experiments. Although methanol extracts contained 48.5 +/- 7.2 mg of
      caffeic acid equivalents and 15.87 +/- 4.6 mg of quercetin equivalents, the
      antioxidant activity, as revealed by DPPH and ABTS assays, was of medium strength
      (EC50 of 306.2 +/- 16.3 and 394.3 +/- 14.8 MUg/mL, respectively). A. theophrasti
      extract inhibits soybean 5-LOX with IC50 value 2.89 +/- 0.2 mg/mL. The
      cytotoxicity of the methanol extract against MCF-7, CCRF-CEM and CEM/ADR5000
      cancer cells resulted in IC50 values of 505.8 +/- 34.7 MUg/mL for MCF-7, 75.6 +/-
      7.1 MUg/mL for CCRF-CEM, and 89.5 +/- 13.4 MUg/mL for CEM/ADR 5000 cells.

PMID- 25050788
TI  - Assembly of amyloid beta peptides in the presence of fibril seeds: one-pot coarse
      grained molecular dynamics simulations.
AB  - The identification of a secondary nucleation pathway in the early aggregation of
      amyloid peptides suggests that the generation of toxic oligomers involves both
      monomers and preformed fibril seeds. To elucidate the underlying molecular
      mechanism, a set of one-pot coarse-grained molecular dynamics simulations was
      performed to investigate the self-assembly of amyloid beta peptides in the
      presence of fibril seeds. It was observed that fibril seeds alone randomly
      assemble into an elongated protofibril, whereas monomers alone form an elongated
      globular oligomer with various morphologies. In the mixture of monomers and
      fibril seeds, both the self-assembly of monomers into small oligomers and the
      association of monomers and oligomers on the surface of fibril seeds are
      primarily driven by hydrophobic interactions. The cooperativity of conformational
      selection and competition leads to different binding propensity of two
      hydrophobic surfaces of fibril seeds. The molecular architecture of the final
      aggregate shows that the fibril seeds establish the elongated framework, and
      oligomers cover them. Oligomers exposed to the solvent are less compact and
      unstable and can be disassociated from the fibril seeds, providing an origin for
      oligomers generated from the secondary nucleation pathway. 

PMID- 25050790
TI  - Semi-physiological pharmacokinetic-pharmacodynamic (PK-PD) modeling and
      simulation of 5-fluorouracil for thrombocytopenia in rats.
AB  - 1. The aim of this study was to develop a simple pharmacokinetic-pharmacodynamic
      (PK-PD) model that could characterize the complete time-course of alterations in
      platelet counts to predict the onset and degree of thrombocytopenia, which
      severely limits the use of the anticancer agent 5-fluorouracil (5-FU), in rats.
      2. Platelet counts were measured in rats following the intravenous administration
      of various doses of 5-FU for 4 days to obtain data for an analysis of the PK-PD
      model. Our PK-PD model consisted of a two-compartment PK model, with three
      compartments for the PD model and 10 structural PK-PD model parameters. 3. After
      the 5-FU treatment, platelet counts transiently decreased to a nadir level,
      showed a rebound to above the baseline level before recovering to baseline
      levels. Nadir platelet counts and rebounds varied with the AUC0-infinity level.
      The final PK-PD model effectively characterized platelet count data and final PD
      parameters were estimated with high certainty. 4. This PK-PD model and simulation
      may represent a valuable tool for quantifying and predicting the complete time
      course of alterations in blood cell counts, and could contribute to the
      development of therapeutic strategies with 5-FU and assessments of various novel
      anticancer agents that are difficult to examine in humans.

PMID- 25050789
TI  - Expression of animal anti-apoptotic gene Ced-9 enhances tolerance during Glycine
      max L.-Bradyrhizobium japonicum interaction under saline stress but reduces
      nodule formation.
AB  - The mechanisms by which the expression of animal cell death suppressors in
      economically important plants conferred enhanced stress tolerance are not fully
      understood. In the present work, the effect of expression of animal antiapoptotic
      gene Ced-9 in soybean hairy roots was evaluated under root hairs and hairy roots
      death-inducing stress conditions given by i) Bradyrhizobium japonicum inoculation
      in presence of 50 mM NaCl, and ii) severe salt stress (150 mM NaCl), for 30 min
      and 3 h, respectively. We have determined that root hairs death induced by
      inoculation in presence of 50 mM NaCl showed characteristics of ordered process,
      with increased ROS generation, MDA and ATP levels, whereas the cell death induced
      by 150 mM NaCl treatment showed non-ordered or necrotic-like characteristics. The
      expression of Ced-9 inhibited or at least delayed root hairs death under these
      treatments. Hairy roots expressing Ced-9 had better homeostasis maintenance,
      preventing potassium release; increasing the ATP levels and controlling the
      oxidative damage avoiding the increase of reactive oxygen species production.
      Even when our results demonstrate a positive effect of animal cell death
      suppressors in plant cell ionic and redox homeostasis under cell death-inducing
      conditions, its expression, contrary to expectations, drastically inhibited
      nodule formation even under control conditions. 

PMID- 25050791
TI  - Comparison of CYP2D metabolism and hepatotoxicity of the myocardial metabolic
      agent perhexiline in Sprague-Dawley and Dark Agouti rats.
AB  - 1. Perhexiline, a chiral anti-anginal agent, may be useful to develop new
      cardiovascular therapies, despite its potential hepatotoxicity. 2. This study
      compared Dark Agouti (DA) and Sprague-Dawley (SD) rats, as models of
      perhexiline's metabolism and hepatotoxicity in humans. Rats (n = 4/group)
      received vehicle or 200 mg/kg/d of racemic perhexiline maleate for 8 weeks.
      Plasma and liver samples were collected to determine concentrations of
      perhexiline and its metabolites, hepatic function and histology. 3. Median
      (range) plasma and liver perhexiline concentrations in SD rats were 0.09 (0.04
      0.13) mg/L and 5.42 (0.92-8.22) ng/mg, respectively. In comparison, DA rats
      showed higher (p < 0.05) plasma 0.50 (0.16-1.13) mg/L and liver 24.5 (9.40-54.7)
      ng/mg perhexiline concentrations, respectively, 2.5- and 3.7-fold higher cis-OH
      perhexiline concentrations, respectively (p < 0.05), and lower plasma metabolic
      ratio (0.89 versus 1.55, p < 0.05). In both strains, the (+):(-) enantiomer ratio
      was 2:1. Perhexiline increased plasma LDH concentrations in DA rats (p < 0.05),
      but had no effect on plasma biochemistry in SD rats. Liver histology revealed
      lower glycogen content in perhexiline-treated SD rats (p < 0.05), but no effects
      on lipid content in either strain. 4. DA rats appeared more similar to humans
      with respect to plasma perhexiline concentrations, metabolic ratio,
      enantioselective disposition and biochemical changes suggestive of perhexiline
      induced toxicity.

PMID- 25050792
TI  - Surface reaction of SnII on goethite (alpha-FeOOH): surface complexation, redox
      reaction, reductive dissolution, and phase transformation.
AB  - To elucidate the potential risk of (126)Sn migration from nuclear waste
      repositories, we investigated the surface reactions of Sn(II) on goethite as a
      function of pH and Sn(II) loading under anoxic condition with O2 level < 2 ppmv.
      Tin redox state and surface structure were investigated by Sn K edge X-ray
      absorption spectroscopy (XAS), goethite phase transformations were investigated
      by high-resolution transmission electron microscopy and selected area electron
      diffraction. The results demonstrate the rapid and complete oxidation of Sn(II)
      by goethite and formation of Sn(IV) (1)E and (2)C surface complexes. The
      contribution of (2)C complexes increases with Sn loading. The Sn(II) oxidation
      leads to a quantitative release of Fe(II) from goethite at low pH, and to the
      precipitation of magnetite at higher pH. To predict Sn sorption, we applied
      surface complexation modeling using the charge distribution multisite
      complexation approach and the XAS-derived surface complexes. Log K values of 15.5
      +/- 1.4 for the (1)E complex and 19.2 +/- 0.6 for the (2)C complex consistently
      predict Sn sorption across pH 2-12 and for two different Sn loadings and confirm
      the strong retention of Sn(II) even under anoxic conditions. 

PMID- 25050793
TI  - Structural correlation method for model reduction and practical estimation of
      patient specific parameters illustrated on heart rate regulation.
AB  - We consider the inverse and patient specific problem of short term (seconds to
      minutes) heart rate regulation specified by a system of nonlinear ODEs and
      corresponding data. We show how a recent method termed the structural correlation
      method (SCM) can be used for model reduction and for obtaining a set of
      practically identifiable parameters. The structural correlation method includes
      two steps: sensitivity and correlation analysis. When combined with an
      optimization step, it is possible to estimate model parameters, enabling the
      model to fit dynamics observed in data. This method is illustrated in detail on a
      model predicting baroreflex regulation of heart rate and applied to analysis of
      data from a rat and healthy humans. Numerous mathematical models have been
      proposed for prediction of baroreflex regulation of heart rate, yet most of these
      have been designed to provide qualitative predictions of the phenomena though
      some recent models have been developed to fit observed data. In this study we
      show that the model put forward by Bugenhagen et al. can be simplified without
      loss of its ability to predict measured data and to be interpreted
      physiologically. Moreover, we show that with minimal changes in nominal parameter
      values the simplified model can be adapted to predict observations from both rats
      and humans. The use of these methods make the model suitable for estimation of
      parameters from individuals, allowing it to be adopted for diagnostic procedures.

PMID- 25050794
TI  - Relationship between exploitation, oscillation, MSY and extinction.
AB  - We give answers to two important problems arising in current fisheries: (i) how
      maximum sustainable yield (MSY) policy is influenced by the initial population
      level, and (ii) how harvesting, oscillation and MSY are related to each other in
      prey-predator systems. To examine the impact of initial population on
      exploitation, we analyze a single species model with strong Allee effect. It is
      found that even when the MSY exists, the dynamic solution may not converge to the
      equilibrium stock if the initial population level is higher but near the critical
      threshold level. In a prey-predator system with Allee effect in the prey species,
      the initial population does not have such important impact neither on MSY nor on
      maximum sustainable total yield (MSTY). However, harvesting the top predator may
      cause extinction of all species if odd number of trophic levels exist in the
      ecosystem. With regard to the second problem, we study two prey-predator models
      and establish that increasing harvesting effort either on prey, predator or both
      prey and predator destroys previously existing oscillation. Moreover, equilibrium
      stock both at MSY and MSTY level is stable. We also discuss the validity of found
      results to other prey-predator systems.

PMID- 25050795
TI  - Do actions speak louder than knowledge? Action manipulation, parental discourse,
      and children's mental state understanding in pretense.
AB  - Studies on pretense mental state understanding in young children have produced
      inconsistent findings. These findings could potentially emerge from the
      confounding influences of action manipulation or the failure to examine possible
      influences on individual children's performances. To address these issues, we
      created a task in which 68 3- and 4-year-olds viewed two actors, side by side, on
      a monitor. Children were told that one actor was knowledgeable about a specific
      animal, whereas the other actor was not. The actors performed identical movements
      that were either related or unrelated to the animal they were mimicking or
      engaged in different behaviors contradictory to their knowledge. Saliency of
      action was also manipulated by presenting either dynamic images or a paused frame
      of the actors' behavior (i.e., the static condition). Children performed
      similarly on the dynamic and static conditions. Children selected the
      knowledgeable actor more often in the unrelated and related trials but were not
      as successful at selecting the knowledgeable actor when the actor's knowledge
      contradicted the actor's behavior. Therefore, by 3 years of age, some children
      may understand that pretend play involves mental representations and appreciate
      that the mind influences a pretender's behavior. To investigate the observed
      individual differences, we also examined children and parents as they engaged in
      reading and pretense activities prior to data collection. The frequency of
      parents' cognitive mental state utterances strongly predicted performance on the
      mental state task. Individual differences in performance as a result of parental
      language and executive functioning abilities are discussed.

PMID- 25050796
TI  - Dynamic nuclear polarisation NMR of nanosized zirconium phosphate polymer
      fillers.
AB  - Surface functionalisation with organic modifiers of multi-layered zirconium
      phosphate (ZrP) nanoparticles used as polymer fillers can be directly probed by
      dynamic nuclear polarisation NMR, which provides unambiguous evidence of the
      presence of P-O-C chemical bonds at the surface of the ZrP layers, thereby
      confirming successful functionalisation. 

PMID- 25050797
TI  - The increased effectiveness of HIV preventive intervention among men who have sex
      with men and of follow-up care for people living with HIV after 'task-shifting'
      to community-based organizations: a 'cash on service delivery' model in China.
AB  - BACKGROUND: A large number of men who have sex with men (MSM) and people living
      with HIV/AIDS (PLHA) are underserved despite increased service availability from
      government facilities while many community based organizations (CBOs) are not
      involved. We aimed to assess the feasibility and effectiveness of the task
      shifting from government facilities to CBOs in China. METHODS: HIV preventive
      intervention for MSM and follow-up care for PLHA were shifted from government
      facilities to CBOs. Based on 'cash on service delivery' model, 10 USD per MSM
      tested for HIV with results notified, 82 USD per newly HIV cases diagnosed, and
      50 USD per PLHA received a defined package of follow-up care services, were paid
      to the CBOs. Cash payments were made biannually based on the verified results in
      the national web-based HIV/AIDS information system. FINDINGS: After task
      shifting, CBOs gradually assumed preventive intervention for MSM and follow-up
      care for PLHA from 2008 to 2012. HIV testing coverage among MSM increased from
      4.1% in 2008 to 22.7% in 2012. The baseline median CD4 counts of newly diagnosed
      HIV positive MSM increased from 309 to 397 cells/uL. HIV tests among MSM by CBOs
      accounted for less than 1% of the total HIV tests in Nanjing but the share of HIV
      cases detected by CBOs was 12.4% in 2008 and 43.6% in 2012. Unit cost per HIV
      case detected by CBOs was 47 times lower than that by government facilities. The
      coverage of CD4 tests and antiretroviral therapy increased from 71.1% and 78.6%
      in 2008 to 86.0% and 90.1% in 2012, respectively. CONCLUSION: It is feasible to
      shift essential HIV services from government facilities to CBOs, and to verify
      independently service results to adopt 'cash on service delivery' model. Services
      provided by CBOs are cost-effective, as compared with that by government
      facilities.

PMID- 25050798
TI  - Tunable reversible metallo-hydrogels: a new platform for visual discrimination of
      biothiols.
AB  - By using metallo-hydrogel as a new platform, a simple and straightforward
      selective visual discrimination of cysteine, homocysteine and glutathione from
      each other as well as from other amino acids has been realized. 

PMID- 25050799
TI  - Online spatial normalization for real-time FMRI.
AB  - Real-time functional magnetic resonance imaging (rtfMRI) is a recently emerged
      technique that demands fast data processing within a single repetition time (TR),
      such as a TR of 2 seconds. Data preprocessing in rtfMRI has rarely involved
      spatial normalization, which can not be accomplished in a short time period.
      However, spatial normalization may be critical for accurate functional
      localization in a stereotactic space and is an essential procedure for some
      emerging applications of rtfMRI. In this study, we introduced an online spatial
      normalization method that adopts a novel affine registration (AFR) procedure
      based on principal axes registration (PA) and Gauss-Newton optimization (GN)
      using the self-adaptive beta parameter, termed PA-GN(beta) AFR and nonlinear
      registration (NLR) based on discrete cosine transform (DCT). In AFR, PA provides
      an appropriate initial estimate of GN to induce the rapid convergence of GN. In
      addition, the beta parameter, which relies on the change rate of cost function,
      is employed to self-adaptively adjust the iteration step of GN. The accuracy and
      performance of PA-GN(beta) AFR were confirmed using both simulation and real data
      and compared with the traditional AFR. The appropriate cutoff frequency of the
      DCT basis function in NLR was determined to balance the accuracy and calculation
      load of the online spatial normalization. Finally, the validity of the online
      spatial normalization method was further demonstrated by brain activation in the
      rtfMRI data. 

PMID- 25050800
TI  - Small dense LDL cholesterol measured by homogeneous assay in Japanese healthy
      controls, metabolic syndrome and diabetes patients with or without a fatty liver.
AB  - BACKGROUND: Serum small dense LDL-cholesterol (sdLDL-C) levels in healthy
      controls and the cases with diabetes (T2DM) and metabolic syndrome (MetS) with or
      without a fatty liver in a large, typical Japanese population was determined.
      METHODS: The plasma lipids and lipoproteins, including sdLDL-C by homogeneous
      assay, were determined in controls, MetS and T2DM patients (n=5255). The cases
      with MetS and preliminary MetS (pre-MetS) as well as T2DM and preliminary T2DM
      (pre-DM) were selected based on the Japanese criteria for MetS and T2DM. Fatty
      liver was diagnosed using the ultrasonography. RESULTS: The 75th percentile
      values for sdLDL-C were 27.5mg/dl for men and 23.3mg/dl for women and increased
      with age. The concentrations of sdLDL-C and sdLDL-C/LDL-C were significantly
      higher in pre-MetS and pre-T2DM patients than healthy controls as well as in MetS
      and T2DM patients. Significantly higher sdLDL-C was found in cases with a fatty
      liver than without a fatty liver in all five groups. CONCLUSIONS: Significantly
      elevated sdLDL-C levels were found in pre-MetS, MetS and pre-T2DM, T2DM patients
      compared to the healthy controls. Fatty liver significantly enhanced serum sdLDL
      C levels and the multiple regression analyses ascertained that fatty liver was an
      independent determinant for sdLDL-C.

PMID- 25050801
TI  - Occurrence, sources, and potential human health risks of polycyclic aromatic
      hydrocarbons in agricultural soils of the coal production area surrounding
      Xinzhou, China.
AB  - A comprehensive investigation of the levels, distribution patterns, and sources
      of polycyclic aromatic hydrocarbons (PAHs) in agricultural soils of the coal
      production area surrounding Xinzhou, China, was conducted, and the potential
      human health risks associated with the levels observed were addressed. A total of
      247 samples collected from agricultural soils from the area were analyzed for
      sixteen PAHs, including highly carcinogenic isomers. The PAH concentrations had a
      range of n.d. to 782ngg(-1), with a mean value of 202ngg(-1). The two-three ring
      PAHs were the dominant species, making up 60 percent of total PAHs. Compared with
      the pollution levels and carcinogenic potential risks reported in other studies,
      the soil PAH concentrations in the study area were in the low to intermediate
      range. A positive matrix factorization model indicates that coal/biomass
      combustion, coal and oil combustion, and coke ovens are the primary PAH sources,
      accounting for 33 percent, 26 percent, and 24 percent of total PAHs,
      respectively. The benzo[a]pyrene equivalent (BaPeq) concentrations had a range of
      n.d. to 476ngg(-1) for PAH7c, with a mean value of 34ngg(-1). The BaPeq
      concentrations of PAH7c accounted for more than 99 percent of the ?PAH16, which
      suggests that seven PAHs were major carcinogenic contributors of ?PAH16.
      According to the Canadian Soil Quality Guidelines, only six of the soil samples
      had concentrations above the safe BaPeq value of 600ngg(-1); the elevated
      concentrations observed at these sites can be attributed to coal combustion and
      industrial activities. Exposure to these soils through direct contact probably
      poses a significant risk to human health as a result of the carcinogenic effects
      of PAHs. 

PMID- 25050802
TI  - Toxinotyping of Clostridium perfringens fecal isolates of reintroduced Pere
      David's deer (Elaphurus davidianus) in China.
AB  - Clostridium perfringens is an important pathogen causing sudden death syndrome,
      necrotic enteritis, and gas gangrene in ruminants, especially some deer species.
      Pere David's deer (Elaphurus davidianus) is one of the world's rare species and
      is an endangered and protected species in China. Some Pere David's deer in the
      Chinese Shishou Pere David's Deer Preserve died due to C. perfringens infection.
      We investigated the toxin types and C. perfringens enterotoxin-positive (cpe(+))
      strains of isolated C. perfringens in Pere David's deer in China. We collected
      155 fecal samples from the Beijing Nanhaizi Pere David's Deer Park and the
      Jiangsu Dafeng Pere David's Deer National Nature Reserve between July 2010 and
      July 2011. Bacteria isolated using blood agar and mannitol agar plates were
      identified by Gram staining and nested PCR for 16S rRNA. We isolated C.
      perfringens from 41 fecal samples and used PCR amplification of five toxin genes
      to identify the toxinotypes and the cpe(+) strains of C. perfringens. Twenty-one
      isolates were type A, 15 were type E, and five were type D. Fifteen isolates were
      cpe(+) strains, including eight that were type A and seven that were type E.

PMID- 25050803
TI  - Molecular assessment of Hepatozoon (Apicomplexa: Adeleorina) infections in wild
      canids and rodents from north Africa, with implications for transmission dynamics
      across taxonomic groups.
AB  - Parasites play a major role in ecosystems, and understanding of host-parasite
      interactions is important for predicting parasite transmission dynamics and
      epidemiology. However, there is still a lack of knowledge about the distribution,
      diversity, and impact of parasites in wildlife, especially from remote areas.
      Hepatozoon is a genus of apicomplexan parasites that is transmitted by ingestion
      of infected arthropod vectors. However, alternative modes of transmission have
      been identified such as trophic transmission. Using the 18S rRNA gene as a
      marker, we provide an assessment of Hepatozoon prevalence in six wild canid and
      two rodent species collected between 2003 and 2012 from remote areas in North
      Africa. By combining this with other predator-prey systems in a phylogenetic
      framework, we investigate Hepatozoon transmission dynamics in distinct host taxa.
      Prevalence was high overall among host species (African jerboa Jaculus jaculus
      [17/47, 36%], greater Egyptian jerboa Jaculus orientalis [5/7, 71%], side-striped
      jackal Canis adustus [1/2, 50%], golden jackal Canis aureus [6/32, 18%], pale fox
      Vulpes pallida [14/28, 50%], Ruppell's fox Vulpes rueppellii [6/11, 55%], red fox
      Vulpes vulpes [8/16, 50%], and fennec fox Vulpes zerda [7/11, 42%]). Phylogenetic
      analysis showed further evidence of occasional transmission of Hepatozoon
      lineages from prey to canid predators, which seems to occur less frequently than
      in other predator-prey systems such as between snakes and lizards. Due to the
      complex nature of the Hepatozoon lifecycle (heteroxenous and vector-borne),
      future studies on these wild host species need to clarify the dynamics of
      alternative modes of Hepatozoon transmission and identify reservoir and
      definitive hosts in natural populations. We also detected putative Babesia spp.
      (Apicomplexa: Piroplasmida) infections in two canid species from this region, V.
      pallida (1/28) and V. zerda (1/11).

PMID- 25050804
TI  - Interpretation of plasma selenium data in huemul: response to Flueck et al.

PMID- 25050805
TI  - Mitophagy in viral infections.
AB  - Antiviral innate immune responses and apoptosis are the two major factors
      limiting viral infections. Successful viral infection requires the virus to take
      advantage of the cellular machinery to bypass cellular defenses. Accumulated
      evidences show that autophagy plays a crucial role in cell-to-virus interaction.
      Here, we focus on how viruses subvert mitophagy to favor viral replication by
      mitigating innate immune responses and apoptotic signaling. 

PMID- 25050806
TI  - Adaptive behavior of a redox-active gallium carbenoid in complexes with
      molybdenum.
AB  - A gallium(I) carbenoid derived from redox-active diimine 1,2-bis[(2,6
      diisopropylphenyl)imino]acenaphthene (dpp-bian) in complexes with molybdenum may
      serve either as a neutral [(dpp-bian)Ga:] or an anionic [(dpp-bian)Ga:](-) two
      electron donor depending on the electronic state of the transition metal.

PMID- 25050807
TI  - HMGB1 gene polymorphism is associated with hypertension in Han Chinese
      population.
AB  - BACKGROUND: High-mobility group box 1 protein (HMGB1) acts as a proinflammatory
      cytokine by activating pattern recognition receptors (PRRs), including Toll-like
      receptor 4 (TLR4) and the receptor of AGE (AGER) with oxidative injury. Animal
      study proved that HMGB1 contributed to the pathogenesis of experimental pulmonary
      hypertension (HT) via activation of TLR4. The aim of this study is to test
      whether HMGB1 harbor genetic susceptibility to HT in a Chinese population.
      METHODS: A case-control study comprising 2012 HT cases and 2210 controls was used
      to evaluate the association of three tagging single nucleotide polymorphism
      (tagSNPs) in HMGB1 gene with HT and blood pressure. Logistic regression model was
      used to adjust confounding factor for HT and general linear model (GLM) was
      applied to compare blood pressure levels between genotypes in cases and controls.
      RESULTS: Single locus analysis showed that there was no statistical association
      of three tagSNPs with HT after adjustment for the covariates. Further
      stratification analysis found that rs2249825 was significantly associated with HT
      in >=55 years groups, ORs (95% CI) of additive model and dominant model were
      1.208 (1.029-1.417) and 1.212 (1.020-1.441), and p values were 0.021 and 0.029,
      respectively. Quantitative trait analysis indicated that DBP had a linear
      decrease with the variations of rs2249825 in both untreated HT group (p=0.002)
      and control group (p=0.034) respectively. CONCLUSIONS: Our finding suggests that
      rs2249825 of HMGB1 genetic polymorphisms are significantly associated with HT and
      diastolic blood pressure, and the genetic effect on HT is modulated by age.

PMID- 25050808
TI  - Analysis techniques of lattice fringe images for quantified evaluation of
      pyrocarbon by chemical vapor infiltration.
AB  - Some image analysis techniques are developed for simplifying lattice fringe
      images of deposited pyrocarbon in carbon/carbon composites by chemical vapor
      infiltration. They are mainly the object counting method for detecting the
      optimum threshold, the self-adaptive morphological filtering, the node-separation
      technique for breaking the aggregate fringes, and some post processing algorithms
      for reconstructing the fringes. The simplified fringes are the foundation for
      defining and extracting quantitative nanostructure parameters of pyrocarbon. The
      frequency filter window of a Fourier transform is defined as the circular band
      that retains only those fringes with interlayer distance between 0.3 and 0.45 nm.
      Some judge criteria are set to define topological relation between fringes. For
      example, the aspect ratio and area of fringes are employed to detect aggregate
      fringes. Fringe coaxality and distance between endpoints are used to judge the
      disconnected fringes. The optimum values are determined by using the iterative
      correction techniques. The best cut-off value for the short fringes is chosen
      only when there is a reasonable match between the mean fringe length and the
      value measured by X-ray diffraction. The adopted techniques have been verified to
      be feasible and to have the potential to convert the complex lattice fringe image
      to a set of distinct fringe structures. 

PMID- 25050809
TI  - Cardiac energy metabolism and oxidative stress biomarkers in diabetic rat treated
      with resveratrol.
AB  - Resveratrol (RSV), polyphenol from grape, was studied to evaluate its effects on
      calorimetric parameters, energy metabolism, and antioxidants in the myocardium of
      diabetic rats. The animals were randomly divided into four groups (n = 8): C
      (control group): normal rats; C-RSV: normal rats receiving RSV; DM: diabetic
      rats; and DM-RSV: diabetics rats receiving RSV. Type 1 diabetes mellitus was
      induced with administration of streptozotocin (STZ; 60 mg(-1) body weight, single
      dose, i.p.). After 48 hours of STZ administration, the animals received RSV (1.0
      mg/kg/day) for gavage for 30 days. Food, water, and energy intake were higher in
      the DM group, while administration of RSV caused decreases (p<0.05) in these
      parameters. The glycemia decreased and higher final body weight increased in DM
      RSV when compared with the DM group. The diabetic rats showed higher serum-free
      fatty acid, which was normalized with RSV. Oxygen consumption (VO2) and carbon
      dioxide production (VCO2) decreased (p<0.05) in the DM group. This was
      accompanied by reductions in RQ. The C-RSV group showed higher VO2 and VCO2
      values. Pyruvate dehydrogenase activity was lower in the DM group and normalizes
      with RSV. The DM group exhibited higher myocardial beta-hydroxyacyl coenzyme-A
      dehydrogenase and citrate synthase activity, and RSV decreased the activity of
      these enzymes. The DM group had higher cardiac lactate dehydrogenase compared to
      the DM-RSV group. Myocardial protein carbonyl was increased in the DM group. RSV
      increased reduced glutathione in the cardiac tissue of diabetic animals. The
      glutathione reductase activity was higher in the DM-RSV group compared to the DM
      group. In conclusion, diabetes is accompanied by cardiac energy metabolism
      dysfunction and change in the biomarkers of oxidative stress. The
      cardioprotective effect may be mediated through RVS's ability to normalize free
      fatty acid oxidation, enhance utilization glucose, and control the biomarkers'
      level of oxidative stress under diabetic conditions.

PMID- 25050811
TI  - Bioinformatics on the cloud computing platform Azure.
AB  - We discuss the applicability of the Microsoft cloud computing platform, Azure,
      for bioinformatics. We focus on the usability of the resource rather than its
      performance. We provide an example of how R can be used on Azure to analyse a
      large amount of microarray expression data deposited at the public database
      ArrayExpress. We provide a walk through to demonstrate explicitly how Azure can
      be used to perform these analyses in Appendix S1 and we offer a comparison with a
      local computation. We note that the use of the Platform as a Service (PaaS)
      offering of Azure can represent a steep learning curve for bioinformatics
      developers who will usually have a Linux and scripting language background. On
      the other hand, the presence of an additional set of libraries makes it easier to
      deploy software in a parallel (scalable) fashion and explicitly manage such a
      production run with only a few hundred lines of code, most of which can be
      incorporated from a template. We propose that this environment is best suited for
      running stable bioinformatics software by users not involved with its
      development. 

PMID- 25050810
TI  - Uncoupling between inflammatory and fibrotic responses to silica: evidence from
      MyD88 knockout mice.
AB  - The exact implication of innate immunity in granuloma formation and irreversible
      lung fibrosis remains to be determined. In this study, we examined the lung
      inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In
      comparison to wild-type (WT) mice, we found that MyD88-KO animals developed
      attenuated lung inflammation, neutrophil accumulation and IL-1beta release in
      response to silica. Granuloma formation was also less pronounced in MyD88-KO mice
      after silica. This limited inflammatory response was not accompanied by a
      concomitant attenuation of lung collagen accumulation after silica. Histological
      analyses revealed that while pulmonary fibrosis was localized in granulomas in WT
      animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice.
      Robust collagen accumulation was also observed in mice KO for several other
      components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and
      TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was
      associated with the accumulation of pro-fibrotic regulatory T lymphocytes (T
      regs) and pro-fibrotic cytokine expression (TGF-beta, IL-10 and PDGF-B), not with
      T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88
      related innate immunity is central in the establishment of particle-induced lung
      inflammatory and granuloma responses. The development of lung fibrosis appears
      uncoupled from inflammation and may be orchestrated by a T reg-associated
      pathway. 

PMID- 25050812
TI  - Vocal production learning in bats.
AB  - Echolocating bats exhibit excellent control over their acoustic signals emitted
      and skillfully interpret the returning echoes, allowing orientation and foraging
      in complete darkness. Echolocation may be a preadaptation for sophisticated vocal
      communication with conspecifics and, ultimately, vocal learning processes. In
      humans, the importance of auditory input for correct speech acquisition is
      obvious, whereas vocal production learning is rare and patchily distributed among
      non-human mammals. Bats comprise one of the few mammalian taxa capable of vocal
      production learning, with current behavioral evidence for three species belonging
      to two families; more evidence will probably forthcoming. The taxon's speciose
      nature makes bats well suited for phylogenetically controlled, comparative
      studies on proximate and ultimate mechanisms of mammalian vocal production
      learning. 

PMID- 25050813
TI  - Central pattern generator for vocalization: is there a vertebrate morphotype?
AB  - Animals that generate acoustic signals for social communication are faced with
      two essential tasks: generate a temporally precise signal and inform the auditory
      system about the occurrence of one's own sonic signal. Recent studies of sound
      producing fishes delineate a hindbrain network comprised of anatomically distinct
      compartments coding equally distinct neurophysiological properties that allow an
      organism to meet these behavioral demands. A set of neural characters comprising
      a vocal-sonic central pattern generator (CPG) morphotype is proposed for fishes
      and tetrapods that shares evolutionary developmental origins with pectoral
      appendage motor systems. 

PMID- 25050815
TI  - Investigations into the involvement of leptin in responses to stress.
AB  - Stress is defined as a state that can threaten homeostasis in an organism to
      initiate the adaptive process. Stress mediators, which include the classic
      neuroendocrine hormones and a number of neurotransmitters, cytokines, and growth
      factors, regulate both basal and threatened homeostasis to help control the
      stress. Severity of stress, as well as malfunctioning of stress pathways, may
      impair its controllability, leading to the pathogenesis of psychiatric illnesses
      including depression. Leptin was initially identified as an antiobesity hormone,
      acting as a negative feedback adiposity signal to control energy homeostasis by
      binding to its receptors in the hypothalamus. Accumulating evidence has expanded
      the function of leptin from the control of energy balance to the regulation of
      other physiological and psychological processes. The aim of this paper is to
      evaluate the potential role of leptin in stress controllability. To this end,
      studies on the role of leptin in stress-induced activation of the hypothalamus
      pituitary-adrenocortical axis, feeding behavior, learned helplessness, and other
      depression models have been accumulated. The knowledge accumulated in this
      article may facilitate the development of alternative treatment strategies,
      beyond serotonin and noradrenaline reuptake inhibition, for psychiatric care and
      stress-related disorders. 

PMID- 25050814
TI  - A unique four-hub protein cluster associates to glioblastoma progression.
AB  - Gliomas are the most frequent brain tumors. Among them, glioblastomas are
      malignant and largely resistant to available treatments. Histopathology is the
      gold standard for classification and grading of brain tumors. However, brain
      tumor heterogeneity is remarkable and histopathology procedures for glioma
      classification remain unsatisfactory for predicting disease course as well as
      response to treatment. Proteins that tightly associate with cancer
      differentiation and progression, can bear important prognostic information. Here,
      we describe the identification of protein clusters differentially expressed in
      high-grade versus low-grade gliomas. Tissue samples from 25 high-grade tumors, 10
      low-grade tumors and 5 normal brain cortices were analyzed by 2D-PAGE and
      proteomic profiling by mass spectrometry. This led to identify 48 differentially
      expressed protein markers between tumors and normal samples. Protein clustering
      by multivariate analyses (PCA and PLS-DA) provided discrimination between
      pathological samples to an unprecedented extent, and revealed a unique network of
      deranged proteins. We discovered a novel glioblastoma control module centered on
      four major network hubs: Huntingtin, HNF4alpha, c-Myc and 14-3-3zeta.
      Immunohistochemistry, western blotting and unbiased proteome-wide meta-analysis
      revealed altered expression of this glioblastoma control module in human glioma
      samples as compared with normal controls. Moreover, the four-hub network was
      found to cross-talk with both p53 and EGFR pathways. In summary, the findings of
      this study indicate the existence of a unifying signaling module controlling
      glioblastoma pathogenesis and malignant progression, and suggest novel targets
      for development of diagnostic and therapeutic procedures. 

PMID- 25050816
TI  - Effects of acute social stress on the conditioned place preference induced by
      MDMA in adolescent and adult mice.
AB  - Exposure to social defeat stress increases the rewarding effects of
      psychostimulants in animal models, but its effect on 3,4
      methylenedioxymethylamphetamine (MDMA) reward has received little attention. In
      the present study, we evaluated the influence of social defeat on the rewarding
      effects of MDMA in adolescent [postnatal day (PND) 29-40] and adult (PND 50-61)
      male mice using the conditioned place preference paradigm. Experimental mice were
      exposed to social defeat in an agonistic encounter before each session of
      conditioning with 1.25 or 10 mg/kg of MDMA. The effects of social defeat on
      corticosterone levels and the motor or the anxiogenic effects of MDMA were also
      evaluated. Mice exposed to social defeat during adulthood did not show
      conditioned place preference after conditioning with either dose of MDMA.
      Conversely, social defeat did not affect the anxiogenic and motor effects of
      MDMA. Adult mice exposed to social defeat showed higher levels of corticosterone
      than their controls and adolescent mice. Social stress did not induce behavioural
      effects in adolescent mice. Our results show that stress induced by social defeat
      decreases the sensitivity of adult mice to the rewarding effects of MDMA. 

PMID- 25050817
TI  - An approach to identify SNPs in the gene encoding acetyl-CoA acetyltransferase-2
      (ACAT-2) and their proposed role in metabolic processes in pig.
AB  - The novel liver protein acetyl-CoA acetyltransferase-2 (ACAT2) is involved in the
      beta-oxidation and lipid metabolism. Its comprehensive relative expression, in
      silico non-synonymous single nucleotide polymorphism (nsSNP) analysis, as well as
      its annotation in terms of metabolic process with another protein from the same
      family, namely, acetyl-CoA acyltransferase-2 (ACAA2) was performed in Sus scrofa.
      This investigation was conducted to understand the most important nsSNPs of ACAT2
      in terms of their effects on metabolic activities and protein conformation. The
      two most deleterious mutations at residues 122 (I to V) and 281 (R to H) were
      found in ACAT2. Validation of expression of genes in the laboratory also
      supported the idea of differential expression of ACAT2 and ACAA2 conceived
      through the in silico analysis. Analysis of the relative expression of ACAT2 and
      ACAA2 in the liver tissue of Jeju native pig showed that the former expressed
      significantly higher (P<0.05). Overall, the computational prediction supported by
      wet laboratory analysis suggests that ACAT2 might contribute more to metabolic
      processes than ACAA2 in swine. Further associations of SNPs in ACAT2 with
      production traits might guide efforts to improve growth performance in Jeju
      native pigs. 

PMID- 25050819
TI  - Differences between nicotine-abstinent smokers and non-smokers in terms of
      visuospatial attention and inhibition before and after single-blind nicotine
      administration.
AB  - The cholinergic system is implicated in visuospatial attention and inhibition,
      however the exact role is still unclear. Two key mechanisms in visuospatial
      attention are bias and disengagement. Bias refers to neuronal signals that
      enhance the sensitivity of the sensory cortex, disengagement is the decoupling of
      attention. Previous studies suggest that nicotine affects disengagement and
      (related) inhibition. However the exact relation is still unknown. Furthermore,
      nicotine-abstinence in 'healthy' smokers may resemble some anomalies of
      visuospatial attention and inhibition as seen in Attention Deficit/Hyperactivity
      Disorder (ADHD). Smokers and non-smokers (32 male students) performed in a
      visuospatial cueing (VSC) task, to assess bias and disengagement, and in a stop
      signal task (SST) to assess inhibition. It was expected that nicotine abstinent
      smokers compared to non-smokers, would show poor disengagement (indicated by an
      enhanced validity effect) and poor inhibitory control (indicated by an enhanced
      stop-signal reaction time (SSRT)). It was expected that nicotine would positively
      affect disengagement and inhibition: hypothesis 1 stated that this effect would
      be larger in smokers as opposed to non-smokers, in terms of smoking-related
      deficient inhibitory control. Hypothesis 2 stated the exact opposite, in terms of
      drug-tolerance. Results indicated no baseline differences. Nicotine enhanced
      inhibition more in non-smokers relative to smokers. Integrating the results,
      nicotine-abstinent smokers do not seem to resemble ADHD patients, and do not seem
      to smoke in order to self-medicate a pre-existing deficit pertaining to
      mechanisms of visuospatial attention and inhibition. Nicotine may affect
      inhibition more in non-smokers relative to smokers, consistent with a drug
      tolerance account. 

PMID- 25050820
TI  - Central amygdala nicotinic and 5-HT1A receptors mediate the reversal effect of
      nicotine and MDMA on morphine-induced amnesia.
AB  - The present study was designed to investigate possible involvement of the central
      amygdala (CeA) nicotinic acetylcholine (nACh) and 5-hydroxytryptamine 1A (5-HT1A)
      receptors in the reversal effect of nicotine and 3,4-methylenedioxy-N
      methylamphetamine (MDMA or ecstasy) on morphine-induced amnesia. Two guide
      cannulas were stereotaxically implanted in the CeA regions and a step-through
      passive avoidance task was used for the assessment of memory retrieval in adult
      male Wistar rats. Our results indicated that post-training s.c. administration of
      morphine (3-7-mg/kg) impaired memory retrieval. Pre-test administration of
      nicotine (0.3- and 0.5-mg/kg, s.c.) reversed morphine-induced amnesia. In
      addition, pre-test intra-CeA injection of MDMA (1-2-MUg/rat) with an ineffective
      dose of nicotine (0.1-mg/kg, s.c.) improved memory retrieval, suggesting the
      interactive effect of the drugs on memory formation. It should be noted that that
      pre-test intra-CeA injection of 2-MUg/rat of MDMA by itself produced amnesia.
      Interestingly, pre-test intra-CeA injection of mecamylamine, a nACh receptor
      antagonist (1-2-MUg/rat) or (S)-WAY 100135 (0.25-1-MUg/rat), a selective 5-HT1A
      receptor antagonist inhibited the improvement of morphine-induced amnesia which
      was produced by pre-test co-injection of nicotine and MDMA. Pre-test intra-CeA
      injection of the same doses of MDMA, mecamylamine or (S)-WAY 100135 by itself had
      no effect on morphine-induced amnesia. Moreover, pre-test injection of the same
      doses of mecamylamine or (S)-WAY 100135 into the CeA alone could not change
      memory retrieval. Taken together, it can be concluded that there is a functional
      interaction between morphine, nicotine and MDMA via the CeA nicotinic and
      serotonergic receptor mechanisms in passive avoidance memory retrieval. Moreover,
      cross state-dependent memory retrieval may have been induced between the drugs
      and this probably depends on the rewarding effects of the drugs.

PMID- 25050821
TI  - Cocaine self-administration and extinction alter medullary noradrenergic and
      limbic forebrain cFos responses to acute, noncontingent cocaine injections in
      adult rats.
AB  - Central noradrenergic (NA) signaling contributes critically to multiple
      behavioral effects of cocaine administration, particularly stress- and anxiety
      related effects. The present study examined the ability of acute cocaine to
      induce the immediate early gene product, cFos, in NA neurons and stress-related
      neural circuits in rats that were cocaine-naive, or had a history of cocaine self
      administration with or without extinction. Rats implanted with jugular catheters
      were trained to self-administer cocaine (0.5-mg/kg/infusion), with a subset
      subsequently trained on extinction. Cocaine-naive controls were handled daily.
      After a final day of self-administration, extinction, or handling, rats received
      an i.p. injection of either cocaine (20-mg/kg) or saline, and 90min later were
      anesthetized and perfused. Tissue sections were processed for immunoperoxidase
      labeling of nuclear cFos with either immunoperoxidase or immunofluorescent
      cytoplasmic labeling of dopamine beta hydroxylase or tyrosine hydroxylase. Acute
      cocaine increased the number of activated NA neurons within the caudal nucleus of
      the solitary tract (NTS; A2 cell group) in cocaine-naive and extinguished rats,
      but not in rats that only self-administered. Extinction attenuated cocaine
      induced cFos activation in NA neurons of the caudal ventrolateral medulla (A1/C1
      cell groups), and attenuated cFos within the paraventricular nucleus of the
      hypothalamus, the apex of the central neuroendocrine stress axis. Cocaine
      consistently increased cFos in the bed nucleus of the stria terminalis,
      regardless of history. NA neurons of the locus coeruleus (A6 cell group) were not
      activated after cocaine administration in any experimental group. Thus, the
      ability of cocaine to activate central stress circuitry is altered after cocaine
      self-administration. Our results suggest a unique role for the NTS in cocaine
      induced reinstatement, as extinction training enhanced the ability of cocaine to
      activate NA neurons within this region. These findings suggest central NA systems
      originating in the caudal brainstem as potential targets for the treatment of
      cocaine addiction. 

PMID- 25050822
TI  - Long-term inhibition of Rho-kinase restores the LTP impaired in chronic forebrain
      ischemia rats by regulating GABAA and GABAB receptors.
AB  - We previously demonstrated that inactivation of Rho-kinase by hydroxyfasudil
      could impact N-methyl-d-aspartate (NMDA) excitatory interneurons in the
      hippocampus and attenuate the spatial learning and memory dysfunction of rats
      caused by chronic forebrain hypoperfusion ischemia. Complementary interactions
      between the excitatory neurotransmitter glutamate and the inhibitory
      neurotransmitter GABA form the molecular basis of synaptic plasticity and
      cognitive performance. However, whether the GABAergic inhibitory interneurons are
      involved in the mechanisms underlying these processes remains unclear. Here, we
      further examined the role of GABAergic interneurons in the neuroprotective effect
      of the Rho-kinase inhibitor. Chronic forebrain ischemia was induced in Wistar
      rats by bilateral common carotid artery occlusion (BCAO). The general synaptic
      transmission and long-term potentiation (LTP) of hippocampal CA3 neurons were
      evaluated at 30 days after sham surgery or BCAO. Real-time PCR and Western blot
      analyses were conducted to determine the effect of the Rho-kinase inhibitor
      hydroxyfasudil on GABAergic inhibitory interneuron expression and function after
      ischemia. Hydroxyfasudil showed no significant effect on general synaptic
      transmission, but it could abolish the inhibition of LTP induced by chronic
      forebrain ischemia. Moreover, the mRNA and protein levels of GABAA and GABAB in
      three brain regions after ischemia were markedly decreased, and hydroxyfasudil
      could up-regulate all mRNA and protein expression levels in these areas except
      for GABAA mRNA in the cerebral cortex and striatum. Using phosphorylation
      antibodies against specific sites on the GABAA and GABAB receptors, we further
      demonstrated that hydroxyfasudil could inhibit GABAergic interneuron
      phosphorylation triggered by the theta burst stimulation. In summary, our results
      indicated that the inactivation of Rho-kinase could enhance GABAA and GABAB
      expressions by different mechanisms to guarantee the induction of hippocampal
      LTP, and it could decrease the phosphorylation level of GABAergic inhibitory
      interneurons to promote the LTP induction rate and magnitude, hence improving the
      cognitive deficit suffered after chronic forebrain ischemia.

PMID- 25050823
TI  - Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6
      cells to a liposome model.
AB  - Labile zinc, a tiny fraction of total intracellular zinc that is loosely bound to
      proteins and easily interchangeable, modulates the activity of numerous signaling
      and metabolic pathways. Dietary plant polyphenols such as the flavonoids
      quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling
      molecules. Remarkably, the activities of numerous enzymes that are targeted by
      polyphenols are dependent on zinc. We have previously shown that these
      polyphenols chelate zinc cations and hypothesized that these flavonoids might be
      also acting as zinc ionophores, transporting zinc cations through the plasma
      membrane. To prove this hypothesis, herein, we have demonstrated the capacity of
      QCT and epigallocatechin-gallate to rapidly increase labile zinc in mouse
      hepatocarcinoma Hepa 1-6 cells as well as, for the first time, in liposomes. In
      order to confirm that the polyphenols transport zinc cations across the plasma
      membrane independently of plasma membrane zinc transporters, QCT,
      epigallocatechin-gallate, or clioquinol (CQ), alone and combined with zinc, were
      added to unilamellar dipalmitoylphosphocholine/cholesterol liposomes loaded with
      membrane-impermeant FluoZin-3. Only the combinations of the chelators with zinc
      triggered a rapid increase of FluoZin-3 fluorescence within the liposomes, thus
      demonstrating the ionophore action of QCT, epigallocatechin-gallate, and CQ on
      lipid membrane systems. The ionophore activity of dietary polyphenols may
      underlay the raising of labile zinc levels triggered in cells by polyphenols and
      thus many of their biological actions. 

PMID- 25050825
TI  - Circulating Muscle-specific miRNAs in Duchenne Muscular Dystrophy Patients.
AB  - Noninvasive biomarkers with diagnostic value and prognostic applications have
      long been desired to replace muscle biopsy for Duchenne muscular dystrophy (DMD)
      patients. Growing evidence indicates that circulating microRNAs are biomarkers to
      assess pathophysiological status. Here, we show that the serum levels of six
      muscle-specific miRNAs (miR-1/206/133/499/208a/208b, also known as myomiRs) were
      all elevated in DMD patients (P < 0.01). The receiver operating characteristic
      curves of circulating miR-206, miR-499, miR-208b, and miR-133 levels reflected
      strong separation between Becker's muscular dystrophy (BMD) and DMD patients (P <
      0.05). miR-206, miR-499, and miR-208b levels were positively correlated with both
      age and type IIc muscle fiber content in DMD patients (2-6 years), indicating
      that they might represent the stage of disease as well as the process of
      regeneration. miR-499 and miR-208b levels were correlated with slow and fast
      fiber content and might reflect the ratio of slow to fast fibers in DMD patient
      (>6 years). Fibroblast growth factor, transforming growth factor-beta, and tumor
      necrosis factor-alpha could affect the secretion of myomiRs, suggesting that
      circulating myomiRs might reflect the effects of cytokines and growth factors on
      degenerating and regenerating muscles. Collectively, our data indicated that
      circulating myomiRs could serve as promising biomarkers for DMD diagnosis and
      disease progression. 

PMID- 25050824
TI  - Specific deletion of LDL receptor-related protein on macrophages has skewed in
      vivo effects on cytokine production by invariant natural killer T cells.
AB  - Expression of molecules involved in lipid homeostasis such as the low density
      lipoprotein receptor (LDLr) on antigen presenting cells (APCs) has been shown to
      enhance invariant natural killer T (iNKT) cell function. However, the
      contribution to iNKT cell activation by other lipoprotein receptors with shared
      structural and ligand binding properties to the LDLr has not been described. In
      this study, we investigated whether a structurally related receptor to the LDLr,
      known as LDL receptor-related protein (LRP), plays a role in iNKT cell
      activation. We found that, unlike the LDLr which is highly expressed on all
      immune cells, the LRP was preferentially expressed at high levels on F4/80+
      macrophages (MPhi). We also show that CD169+ MPhis, known to present antigen to
      iNKT cells, exhibited increased expression of LRP compared to CD169- MPhis. To
      test the contribution of MPhi LRP to iNKT cell activation we used a mouse model
      of MPhi LRP conditional knockout (LRP-cKO). LRP-cKO MPhis pulsed with glycolipid
      alpha-galactosylceramide (alphaGC) elicited normal IL-2 secretion by iNKT
      hybridoma and in vivo challenge of LRP-cKO mice led to normal IFN-gamma, but
      blunted IL-4 response in both serum and intracellular expression by iNKT cells.
      Flow cytometric analyses show similar levels of MHC class-I like molecule CD1d on
      LRP-cKO MPhis and normal glycolipid uptake. Survey of the iNKT cell compartment
      in LRP-cKO mice revealed intact numbers and percentages and no homeostatic
      disruption as evidenced by the absence of programmed death-1 and Ly-49 surface
      receptors. Mixed bone marrow chimeras showed that the inability iNKT cells to
      make IL-4 is cell extrinsic and can be rescued in the presence of wild type APCs.
      Collectively, these data demonstrate that, although MPhi LRP may not be necessary
      for IFN-gamma responses, it can contribute to iNKT cell activation by enhancing
      early IL-4 secretion. 

PMID- 25050826
TI  - Inactivation of TEM-1 by avibactam (NXL-104): insights from quantum
      mechanics/molecular mechanics metadynamics simulations.
AB  - The fast and constant development of drug-resistant bacteria represents a serious
      medical emergence. To overcome this problem, the development of drugs with new
      structures and modes of action is urgently needed. In this context, avibactam
      represents a promising, innovative inhibitor of beta-lactamases with a novel
      molecular structure compared to previously developed inhibitors, showing a
      promising inhibitory activity toward a significant number of beta-lactamase
      enzymes. In this work, we studied, at the atomistic level, the mechanisms of
      formation of the covalent complex between avibactam and TEM-1, an experimentally
      well-characterized class A beta-lactamase, using classical and quantum
      mechanics/molecular mechanics (QM/MM) simulations combined with metadynamics. Our
      simulations provide a detailed structural and energetic picture of the molecular
      steps leading to the formation of the avibactam/TEM-1 covalent adduct. In
      particular, they support a mechanism in which the rate-determining step is the
      water-assisted Glu166 deprotonation by Ser70. In this mechanistic framework, the
      predicted activation energy is in good agreement with experimental kinetic
      measurements. Additionally, our simulations highlight the important role of Lys73
      in assisting the Ser70 and Ser130 deprotonations. While based on the specific
      case of the avibactam/TEM-1, the simple protocol we present here can be
      immediately extended and applied to the study of covalent complex formation in
      different enzyme-inhibitor pairs. 

PMID- 25050827
TI  - Effects of an acute bout of exercise on memory in 6th grade children.
AB  - Research supports the positive effects of exercise on cognitive performance by
      children. However, a limited number of studies have explored the effects
      specifically on memory. The purpose of this study was to compare the effects of
      an acute bout of exercise on learning, short-term memory, and long-term memory in
      a sample of children. Children were randomly assigned to an exercise condition or
      to a no-treatment control condition and then performed repeated trials on an
      auditory verbal learning task. In the exercise condition, participants performed
      the PACER task, an aerobic fitness assessment, in their physical education class
      before performing the memory task. In the control condition, participants
      performed the memory task at the beginning of their physical education class.
      Results showed that participants in the exercise condition demonstrated
      significantly better learning of the word lists and significantly better recall
      of the words after a brief delay. There were not significant differences in
      recognition of the words after an approximately 24-hr delay. These results
      provide evidence in a school setting that an acute bout of exercise provides
      benefits for verbal learning and long-term memory. Future research should be
      designed to identify the extent to which these findings translate to academic
      measures. 

PMID- 25050829
TI  - Yolk-shell Fe(0)@SiO2 nanoparticles as nanoreactors for fenton-like catalytic
      reaction.
AB  - Yolk-shell nanoparticles (YSNs) with active metal cores have shown promising
      applications in nanoreactors with excellent catalytic performance. In this work,
      Fe(0)@SiO2 YSNs were synthesized by a sequential "two-solvents" impregnation
      reduction approach. Specifically, FeSO4 aqueous solution was introduced into the
      preformed hollow mesoporous silica spheres (HMSS), dispersed in n-hexane, via a
      "two-solvent" impregnation way. Subsequently, aqueous solution of sodium
      borohydride (NaBH4) was introduced into the cavity of HMSS by the same way,
      leading to the formation of Fe core inside the HMSS through the reaction between
      Fe(2+) and NaBH4. The resulting Fe(0)@SiO2 YSNs possess distinctive structures,
      including active cores, accessible mesoporous channels, protective shells, and
      hollow cavities. To present the catalytic performance of YSNs nanoreactors,
      Fenton-like catalytic oxidation of phenol was chosen as the model catalysis
      reaction. In addition to the Fe(0)@SiO2 YSNs, two other materials were also
      applied to the catalytic system for comparison, including Fe@SiO2 composites with
      iron nanoparticles sticking on the outer shells of HMSS (Fe@SiO2-DI) and bare
      iron nanoparticles without HMSS (bare Fe(0)), respectively. The catalytic results
      show that Fe(0)@SiO2 YSNs exhibit higher catalytic rate toward phenol removal at
      2-fold and 4-fold as compared to that of Fe@SiO2-DI and bare Fe(0), indicating
      the outstanding catalytic property of YSNs nanoreactors. To further clarify the
      relationship between catalytic properties and structural characteristics, the
      adsorption experiments of the three samples were also performed in the absence of
      H2O2. Other than catalytic results, Fe(0)@SiO2 YSNs show slightly higher
      adsorption efficiency than the other two samples, indicating the accessibility of
      nanoreactors. This result demonstrates that the removal of phenol in the
      oxidation system of Fe(0)@SiO2 YSNs may have contributed to the structure
      enhanced effect of YSNs as nanoreactors. 

PMID- 25050828
TI  - Short communication: Molecular epidemiology, phylogeny, and phylodynamics of
      CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in
      Siberia.
AB  - The HIV-1 epidemic in Russia is dominated by the former Soviet Union subtype A
      (A(FSU)) variant, but other genetic forms are circulating in the country. One is
      the recently described CRF63_02A1, derived from recombination between a CRF02_AG
      variant circulating in Central Asia and A(FSU), which has spread in the
      Novosibirsk region, Siberia. Here we phylogenetically analyze pol and env
      segments from 24 HIV-1 samples from the Novosibirsk region collected in 2013,
      with characterization of three new near full-length genome CRF63_02A1 sequences,
      and estimate the time of the most recent common ancestor (tMRCA) and the
      demographic growth of CRF63_02A1 using a Bayesian method. The analyses revealed
      that CRF63_02A1 is highly predominant in the Novosibirsk region (81.2% in pol
      sequences) and is transmitted both among injecting drug users and by heterosexual
      contact. Similarity searches with database sequences combined with phylogenetic
      analyses show that CRF63_02A1 is circulating in East Kazakhstan and the Eastern
      area of Russia bordering China. The analyses of near full-length genome sequences
      show that its mosaic structure is more complex than reported, with 18
      breakpoints. The tMRCA of CRF63_02A1 was estimated around 2006, with exponential
      growth in 2008-2009 and subsequent stabilization. These results provide new
      insights into the molecular epidemiology, phylogeny, and phylodynamics of
      CRF63_02A1.

PMID- 25050830
TI  - Comparing a parent-report and a performance-based measure of children's motor
      skill abilities: are they associated?
AB  - Both parent-report and performance-based assessment approaches are used in
      occupational therapy practice to gather information about children's motor skill
      abilities. This study investigated whether an association existed between the
      Bruininks-Oseretsky Test of Motor Proficiency- 2(nd) edition (BOT-2), a
      performance-based motor-skill assessment and the Movement Assessment Battery for
      Children - 2(nd) edition (MABC-2) Checklist, a parent-report scale of children's
      motor abilities. A convenience sample of 50 typically developing children aged 7
      16 years were recruited. Scores from the BOT-2 and MABC-2 Checklist were analyzed
      using Spearman's rho correlations and linear regression analyses with several
      significant correlations found. The following BOT-2 derived scores were
      correlated with the MABC-2 Checklist: (1) BOT-2 subscales of Fine Motor Precision
      (rho = .33, p < .05), Manual Dexterity (rho = .28, p < .05), and Upper-Limb
      Coordination (rho = .39, p < .05); (2) the BOT-2 motor composite areas of Fine
      Motor Control (rho = .30, p < .05), and Manual Coordination (rho = .33, p < .05);
      and (3) the BOT-2 Short Form total score (rho = .28, p < .05). Regression
      analysis indicated that the MABC-2 Checklist was significantly associated with
      the BOT-2 Fine Manual Control and Manual Coordination composite area scores.

PMID- 25050831
TI  - Photoinduced electron transfer pathways in hydrogen-evolving reduced graphene
      oxide-boosted hybrid nano-bio catalyst.
AB  - Photocatalytic production of clean hydrogen fuels using water and sunlight has
      attracted remarkable attention due to the increasing global energy demand.
      Natural and synthetic dyes can be utilized to sensitize semiconductors for solar
      energy transformation using visible light. In this study, reduced graphene oxide
      (rGO) and a membrane protein bacteriorhodopsin (bR) were employed as building
      modules to harness visible light by a Pt/TiO2 nanocatalyst. Introduction of the
      rGO boosts the nano-bio catalyst performance that results in hydrogen production
      rates of approximately 11.24 mmol of H2 (MUmol protein)(-1) h(-1).
      Photoelectrochemical measurements show a 9-fold increase in photocurrent density
      when TiO2 electrodes were modified with rGO and bR. Electron paramagnetic
      resonance and transient absorption spectroscopy demonstrate an interfacial charge
      transfer from the photoexcited rGO to the semiconductor under visible light. 

PMID- 25050832
TI  - Inhibitory effects of Rubi Fructus extracts on hepatic steatosis development in
      high-fat diet-induced obese mice.
AB  - The present study was performed to investigate the potential effects of the
      unripened dried fruit of Rubus coreanus Miq., Rubi Fructus (RF), on hepatic
      steatosis and lipid metabolism in mice fed with a high-fat diet (HFD) known to
      induce obesity and hyperlipidaemia. Rubi Fructus extract (RFex) fed mice
      demonstrated a reduced body weight and adipose tissue weight. RFex fed mice also
      demonstrated decreased aminotransferase levels, lipid contents [triglyceride
      (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C)],
      leptin content and increased high-density lipoprotein-cholesterol (HDL-C)
      contents in the plasma. These effects were accompanied by a decreased expression
      of lipogenic genes, including sterol regulatory element binding protein-1c, liver
      X receptor, fatty acid synthase (FAS), acetyl-CoA carboxylase, cluster of
      differentiation 36, lipoprotein lipase and decreased lipogenic enzyme FAS and 3
      hydroxy-3 methylglutamyl coenzyme reductase enzyme activities, while elevating
      carnitine palmitoyltrasferase-1 activity. Based on these results, the present
      study hypothesized that the inhibitory effect on hepatic steatosis of RFex is the
      result of the suppression of lipid synthesis in mice fed with HFD, suggesting
      that RFex may be beneficial in preventing hepatic steatosis and liver
      lipotoxicity.

PMID- 25050833
TI  - Alternatively spliced variants of the regucalcin gene in various human normal and
      tumor tissues.
AB  - Regucalcin plays a pivotal role as a suppressor protein in signal transduction in
      various cell types. The regucalcin gene, which is localized on the X chromosome,
      consists of 7 exons and 6 introns. Decreased liver regucalcin gene expression has
      been suggested to play a suppressive role in the development of hepatocellular
      carcinogenesis in animal models. This study was undertaken to determine the
      changes in regucalcin gene expression in various human normal and tumor tissues,
      including liver, kidney, brain and lung tissues. The full-length and
      alternatively spliced variants of regucalcin mRNA were found to be expressed in
      various human tissues. This expression was suppressed in tumor tissues of
      hepatocellular carcinoma, kidney transitional cell carcinoma, brain malignant
      meningioma and lung non-small cell carcinoma. The full-length regucalcin protein
      was found to be highly expressed in normal human liver and kidney tissues; its
      expression was suppressed, however, in the liver and kidney tumor tissues. The
      spliced variant proteins were found to be expressed in the normal liver and
      kidney tissues, and decreased in the tumor tissues. Such alternative variants
      were not observed in the liver and kidneys of rats and mice. The alternatively
      spliced variants of the regucalcin gene were found to be expressed in various
      human normal and tumor tissues.

PMID- 25050834
TI  - Persistent differences in asthma self-efficacy by race, ethnicity, and income in
      adults with asthma.
AB  - OBJECTIVE: The objective of this population-based study was to determine if and
      to what extent there are differences in asthma self-efficacy by race/ethnicity
      and income, and whether health status, levels of acculturation, and health care
      factors may explain these differences. METHODS: We conducted a secondary data
      analysis of asthma self-efficacy using the 2009 and 2011-2012 California Health
      Interview Survey, in adults with asthma (n=7874). In order to examine if and how
      the effect of race/ethnicity and income on asthma self-efficacy may have been
      altered by health status, acculturation, and health care factors, we used staged
      multivariable logistic regression models. We conducted mediation analyses to
      evaluate which of these factors might mediate disparities in self-efficacy by
      race/ethnicity and income. RESULTS: 69.8% of adults reported having high asthma
      self-efficacy. Latinos (OR 0.66; 95% CI 0.51-0.86), African-Americans (OR 0.50;
      95% CI 0.29-0.83), American Indian/Alaskan Natives (OR 0.55; 95% CI 0.31-0.98)
      and Asian/Pacific Islanders (OR 0.34; 95% CI 0.23-0.52) were less likely to
      report high self-efficacy compared to Whites. Individuals with income below the
      federal poverty level (OR 0.56; 95% CI 0.40-0.78) were less likely to report high
      self-efficacy compared to higher income individuals. The relationship between
      income and self-efficacy was no longer significant after further adjustment for
      health care factors; however, the differences in race and ethnicity persisted.
      Receiving an asthma management plan mediated the relationship in certain
      subgroups. CONCLUSIONS: Addressing modifiable health care factors may play an
      important role in reducing disparities in asthma self-efficacy.

PMID- 25050835
TI  - Association between quality of life in parents and components of asthma control
      in children.
AB  - OBJECTIVE: Describe the association between parents' quality of life and the two
      components of asthma control in children: impairment and risk. METHODS: Cross
      sectional study with children between 4 and 14 years of age with active asthma
      recruited at primary care centers in Spain. Asthma control was assessed according
      to the Third National Asthma Expert Panel Report, classifying "impairment" in
      three levels (well-controlled asthma, partially controlled, and poorly
      controlled), and "risk" as high or low. The parents' quality of life was
      evaluated using the specific Family Impact of Childhood Bronchial Asthma
      Questionnaire instrument (IFABI-R). The association between asthma control and
      the parents' quality of life was analyzed using multivariate regression models
      adjusted for other social and family variables. RESULTS: Data from 408 children
      were analyzed. The parents' quality of life was affected in the partially
      controlled asthma group when compared with well-controlled asthma, as showed by
      an increase in IFABI-R scores in all dimensions: functional 17.2% (p < 0.001),
      emotional 10.4% (p = 0.021), and socio-occupational 6.8% (p = 0.056). The
      differences were higher in poorly controlled asthma compared with well-controlled
      asthma: functional 24.3% (p = 0.001), emotional 18.9% (p = 0.008), and socio
      occupational 11.5% (p = 0.036). The "risk" component was independently associated
      with the parents' quality of life. Of all the elements used to assess the
      control, the only one independently associated with the parents' quality of life
      was recurrent asthma crisis. CONCLUSIONS: In asthma control, both "impairment"
      and "risk" in children are gradually associated with the parents' quality of
      life. The global assessment of the control surpasses the importance of each
      individual element used in this assessment.

PMID- 25050836
TI  - Synergistic effect of celecoxib in tumor necrosis factor-related apoptosis
      inducing ligand treatment in osteosarcoma cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is under clinical
      development as a cancer therapeutic as it has been shown to induce apoptosis in
      numerous types of cancer cells without significant toxicity towards normal cells.
      However, the majority of osteosarcoma (OS) tumors are resistant to TRAIL. Thus,
      the development of cancer therapeutics that overcome TRAIL resistance is
      required. In the present study, celecoxib (CXB), a non-steroidal anti
      inflammatory drug, was administered in combination with TRAIL to induce cell
      apoptosis and the doses of the two drugs were simultaneously reduced. The effects
      of this combination treatment were examined in MG-63 human OS cancer cell lines
      in culture. Assays of proliferation, apoptosis and tumor growth were performed,
      along with analysis of the proteins involved. The results revealed that CXB
      sensitized TRAIL-resistant MG-63 OS cells to TRAIL-induced apoptosis through
      downregulation of cellular B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein,
      caspase-8 and caspase-3. Furthermore, combination treatment reduced tumor growth
      in a nude rat model. In conclusion, the experimental results provided evidence
      that the combined administration of CXB and TRAIL is potentially a novel
      treatment method of OS tumors.

PMID- 25050837
TI  - Impact of environmental factors and biological soil crust types on soil
      respiration in a desert ecosystem.
AB  - The responses of soil respiration to environmental conditions have been studied
      extensively in various ecosystems. However, little is known about the impacts of
      temperature and moisture on soils respiration under biological soil crusts. In
      this study, CO2 efflux from biologically-crusted soils was measured continuously
      with an automated chamber system in Ningxia, northwest China, from June to
      October 2012. The highest soil respiration was observed in lichen-crusted soil
      (0.93 +/- 0.43 umol m-2 s-1) and the lowest values in algae-crusted soil (0.73 +/
      0.31 umol m-2 s-1). Over the diurnal scale, soil respiration was highest in the
      morning whereas soil temperature was highest in the midday, which resulted in
      diurnal hysteresis between the two variables. In addition, the lag time between
      soil respiration and soil temperature was negatively correlated with the soil
      volumetric water content and was reduced as soil water content increased. Over
      the seasonal scale, daily mean nighttime soil respiration was positively
      correlated with soil temperature when moisture exceeded 0.075 and 0.085 m3 m-3 in
      lichen- and moss-crusted soil, respectively. However, moisture did not affect on
      soil respiration in algae-crusted soil during the study period. Daily mean
      nighttime soil respiration normalized by soil temperature increased with water
      content in lichen- and moss-crusted soil. Our results indicated that different
      types of biological soil crusts could affect response of soil respiration to
      environmental factors. There is a need to consider the spatial distribution of
      different types of biological soil crusts and their relative contributions to the
      total C budgets at the ecosystem or landscape level.

PMID- 25050838
TI  - Cellular strategies to promote vascularisation in tissue engineering
      applications.
AB  - Vascularisation is considered to be one of the greatest challenges in tissue
      engineering. Different strategies exist but cell-based approaches have emerged as
      a promising therapy to achieve successful vascularisation. The use of endothelial
      cells to engineer vascularised tissues has been extensively investigated. This
      field of research has evolved with the discovery of endothelial progenitor cells,
      a subpopulation with a high regenerative potential. However, the survival of
      endothelial cell populations alone seems to be impaired. To overcome this
      problem, co-culture systems, involving supporting cells, like mural cells,
      fibroblasts, or more tissue-specific cells have been developed. Endothelial cells
      benefit from the extracellular matrix components and growth factors produced by
      the supporting cells, which results in neovessel stabilisation and maturation.
      The use of endothelial progenitor cells in co-culture systems appears to be a
      promising strategy to promote vascularisation in approaches of increasing
      complexity. Herein, the authors provide an overview of the cellular strategies
      that can be used for increasing vascularisation in tissue engineering and
      regeneration. 

PMID- 25050839
TI  - Retrospective analysis of synthetic cannabinoids in serum samples--epidemiology
      and consumption patterns.
AB  - Herbal mixtures contain synthetic cannabinoids, which can cause severe
      intoxications. Due to the great variety and the changing spectrum of substances
      on the drug market, prevalence data are limited, and data on prevalence rates of
      synthetic cannabinoids in forensic cases are not available. The present study was
      performed to survey the prevalence of synthetic cannabinoids in cases of traffic
      and criminal offences in the German state Hesse in 2010. The applied analytical
      method covered all synthetic cannabinoids on the drug market at that time, and
      with 20% of the blood samples (422 out of 2201) a representative number was
      reanalyzed. In twelve samples synthetic cannabinoids were identified and a
      prevalence of 2.8% was estimated. Consumption patterns showed predominantly cases
      of multi-drug consumption (10 cases); the combination with cannabis or alcohol
      was frequent (four cases each). The observed deficits were moderate with the
      exception of aggravation of paranoia in one case. The symptoms were either
      compatible with the effects of cannabinoid agonists or attributable to alcohol or
      other drugs found in the blood samples. Our current analytical strategy is to
      perform such analyses only in cases where use is suspected or where symptoms are
      not explained by routine toxicological analyses. Hence, the positive rate is
      rather low highlighting the need to keep up with the developments on the drug
      market and to establish sensitive screening methods covering a broad range of
      substances that can be updated fast, e.g., relying on collections of mass
      spectrometric reference data. 

PMID- 25050840
TI  - Pharmacokinetic interactions between ethanol and heroin: a study on post-mortem
      cases.
AB  - INTRODUCTION: Ethanol and heroin are both depressant drugs on the central nervous
      system, and combined use is known to be dangerous due to pharmacodynamic
      interactions, leading to an even higher risk of respiratory depression and death.
      In addition, previous studies have suggested a pharmacokinetic interaction
      between ethanol and the metabolism of heroin. The aim of the present study was to
      investigate if there was a pharmacokinetic interaction between heroin and
      ethanol, by comparing concentrations of heroin metabolites in cases with and
      without ethanol, as detected in blood samples collected from a large material of
      forensic autopsy cases. METHODS: The material consisted of 1583 forensic autopsy
      cases, all containing 6-monoacetylmorphine (6-MAM), as evidence of heroin intake,
      in either blood or urine samples, from the time period between the 1st of January
      2000 and the 31st of December 2012. Due to the high risk of post-mortem ethanol
      formation in cases revealing blood ethanol concentrations between 0.1 and
      0.30/00, these cases were excluded from the study, along with cases where the
      analysis for ethanol was missing. After this exclusion of cases, the material
      (n=1474) was divided into two groups; one group where ethanol was not detected in
      blood (n=1160), and another group where ethanol was detected in blood at or above
      the concentration of 0.40/00 (n=314). Furthermore, the material was also divided
      into two other subgroups; one group where 6-MAM was detected in blood samples,
      indicating a very recent intake of heroin, and another group where 6-MAM was
      detected in the urine, but not in blood, indicating a less recent heroin intake.
      RESULTS: The concentration ratios of morphine/6-MAM, morphine-3-glucuronide
      (M3G)/morphine, and morphine-6-glucuronide (M6G)/morphine in blood samples, were
      all significantly lower in the ethanol positive cases compared with that of the
      ethanol negative cases. For the subgroup of cases revealing a very recent intake
      of heroin (n=645), only the morphine/6-MAM ratio was significantly lower in the
      ethanol positive cases than in the ethanol negative cases. For the subgroup of
      cases with a less recent heroin intake (n=817), lower M3G/morphine and
      M6G/morphine ratios were found among the ethanol positive cases. CONCLUSIONS: The
      results indicate that ethanol inhibits two steps in the heroin metabolism; the
      hydrolysis of 6-MAM to morphine, and the glucuronidation of morphine to M3G and
      M6G. This pharmacokinetic interaction could further complicate the outcome after
      combined use of heroin and ethanol, in addition to the already well-known
      pharmacodynamic interactions.

PMID- 25050841
TI  - Molecular identification of adult and juvenile linyphiid and theridiid spiders in
      Alpine glacier foreland communities.
AB  - In glacier forelands spiders constitute a large proportion of the invertebrate
      community. Therefore, it is important to be able to determine the species that
      can be found in these areas. Linyphiid and theridiid spider identification is
      currently not possible in juvenile specimens using traditional morphological
      based methods, however, a large proportion of the population in these areas are
      usually juveniles. Molecular methods permit identification of species at
      different life stages, making juvenile identification possible. In this study we
      tested a molecular tool to identify the 10 most common species of Linyphiidae and
      Theridiidae found in three glacier foreland communities of the Austrian Alps. Two
      multiplex PCR systems were developed and over 90% of the 753 field-collected
      spiders were identified successfully. The species targeted were found to be
      common in all three valleys during the summer of 2010. A comparison between the
      molecular and morphological data showed that although there was a slight
      difference in the results, the overall outcome was the same independently of the
      identification method used. We believe the quick and reliable identification of
      the spiders via the multiplex PCR assays developed here will aid the study of
      these families in Alpine habitats. 

PMID- 25050842
TI  - Liquid-liquid phase transition in quasi-two-dimensional supercooled silicon.
AB  - Anomalies of the local structural order in quasi-two-dimensional liquid silicon
      upon cooling are investigated. Results show that the appearance of the left
      subpeak in pair correlation functions is the signature of the liquid-liquid phase
      transition (LLPT). The structural origin of the LLPT is the formation of a
      crystal-like ordered structure with a short-range scale, which in turn forms the
      local well-organized paracrystalline region. Unlike in the bulk liquid silicon,
      the stages of the LLPT and liquid-solid phase transition (LSPT) in the quasi-two
      dimensional liquid silicon do not overlap. The crystal-like ordered structures
      formed in the LLPT are precursors which are prepared for the subsequent LSPT.
      Also observed was a strong interconnection between the local well-organized
      paracrystalline region and the transition from the typical metal to the semimetal
      in the two-dimensional silicon. This study will aid in better understanding of
      the essential phase change in two-dimensional liquid silicon. 

PMID- 25050843
TI  - Concerted amidation of activated esters: reaction path and origins of selectivity
      in the kinetic resolution of cyclic amines via N-heterocyclic carbenes and
      hydroxamic acid cocatalyzed acyl transfer.
AB  - The N-heterocyclic carbene and hydroxamic acid cocatalyzed kinetic resolution of
      cyclic amines generates enantioenriched amines and amides with selectivity
      factors up to 127. In this report, a quantum mechanical study of the reaction
      mechanism indicates that the selectivity-determining aminolysis step occurs via a
      novel concerted pathway in which the hydroxamic acid plays a key role in
      directing proton transfer from the incoming amine. This modality was found to be
      general in amide bond formation from a number of activated esters including those
      generated from HOBt and HOAt, reagents that are broadly used in peptide coupling.
      For the kinetic resolution, the proposed model accurately predicts the faster
      reacting enantiomer. A breakdown of the steric and electronic control elements
      shows that a gearing effect in the transition state is responsible for the
      observed selectivity. 

PMID- 25050844
TI  - Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance
      invasiveness.
AB  - Anaphylatoxin C5a indirectly fosters cancer cells through recruitment of myeloid
      derived suppressor cells (MDS) for inhibiting antitumor CD8+ T cells and
      induction of neovascularization. We recently found activation of cancer cells by
      C5a directly via the C5a-receptor (C5aR; CD88) to enhance invasiveness. Thus, C5a
      possibly contributes to cancer progression rather than elimination. C5a
      generation in cancer tissues has been reported; however, the mechanism is not
      fully elucidated. Cancer cell expression of complement regulatory molecules
      suggests inefficient C5a generation through activation of the complement system
      in response to cancer cells. To explore another C5a generation mechanism in
      cancer tissues, we examined cancer cells for C5a-releasing activity from C5. C5a
      was present in C5-supplemented culture media of cancer cells including C5aR
      expressing cells, and the media enhanced C5aR-expressing cancer cell invasion,
      which was abolished by anti-C5a antibody. The C5a-releasing activity was absent
      in the supernatants of the media and was inhibited by aprotinin, a serine
      protease inhibitor, and decanoyl-Arg-Val-Lys-Arg-chloromethylketone but not by
      inhibitors specific for cysteine, acid, or metal proteases. These results
      indicated C5a release from C5 by a cancer cell membrane-bound serine protease
      that can cleave peptide bonds at the carboxy-terminal site of paired basic amino
      acid residues. Cancer cell C5a release from the complement-immobilized plasma
      supported feasibility of this cancer cell protease-dependent C5a generation in
      cancer tissues. The new mechanism of C5a generation suggests self-activation of
      C5aR-expressing cancer cells to enhance invasiveness and induction of MDS
      recruitment and neovascularization to create a microenvironment favorable for
      cancer progression. 

PMID- 25050846
TI  - An assessment of the reliability of dose coefficients for intakes of
      radionuclides by members of the public.
AB  - This paper summarises work undertaken on behalf of the Environment Agency for
      England to quantify uncertainties resulting from internal exposures to a number
      of radionuclides considered significant because of their anthropogenic origin,
      namely: (238)U, (226)Ra, (239)Pu, (241)Am, (137)Cs, (90)Sr, (131)I, (129)I and
      (3)H. Uncertainties in the biokinetic models that are used to calculate the
      retention and excretion of radionuclides are derived in order to calculate
      distributions of effective dose per unit intake following their inhalation or
      ingestion by members of the UK public. The central values and ranges of the
      distributions are used to inform the derivation of uncertainty factors (UFs) for
      the different dose coefficients, which can be used to assess reliability. These
      represent uncertainties inherent in the structures of the biokinetic models and
      their parameter values. The inferred UF values are typically around 2-3 for
      ingestion and 2-6 for inhalation for all age groups, and are comparable to UF
      values inferred from published studies. It is instructive to consider these
      ranges alongside the likely levels of exposure that are expected from the
      radionuclides considered (the microsievert range) and the dose limit of planned
      exposures for members of the public (1000 MUSv). 

PMID- 25050845
TI  - TGF-beta/Smad signaling during hepatic fibro-carcinogenesis (review).
AB  - After hepatitis virus infection, plasma transforming growth factor (TGF)-beta
      increases in either the acute or chronic inflammatory microenvironment. Although
      TGF-beta is upregulated in patients with hepatocellular carcinoma, it is one of
      the most potent growth inhibitors for hepatocytes. This cytokine also upregulates
      extracellular matrix (ECM) production of hepatic stellate cells. Therefore, TGF
      beta is considered to be the major factor regulating liver carcinogenesis and
      accelerating liver fibrosis. Smad2 and Smad3 act as the intracellular mediators
      of TGF-beta signal transduction pathway. We have generated numerous antibodies
      against individual phosphorylation sites in Smad2/3, and identified 3 types of
      phosphorylated forms (phospho-isoforms): COOH-terminally phosphorylated Smad2/3
      (pSmad2C and pSmad3C), linker phosphorylated Smad2/3 (pSmad2L and pSmad3L) and
      dually phosphorylated Smad2/3 (pSmad2L/C and pSmad3L/C). These Smad phospho
      isoforms are categorized into 3 groups: cytostatic pSmad3C signaling, mitogenic
      pSmad3L signaling and invasive/fibrogenic pSmad2L/C signaling. In this review, we
      describe differential regulation of TGF-beta/Smad signaling after acute or
      chronic liver injuries. In addition, we consider how chronic inflammation
      associated with hepatitis virus infection promotes hepatic fibrosis and
      carcinogenesis (fibro-carcinogenesis), focusing on alteration of Smad phospho
      isoform signaling. Finally, we show reversibility of Smad phospho-isoform
      signaling after therapy against hepatitis virus infection. 

PMID- 25050847
TI  - Peptic ulcer disease in Helicobacter pylori-infected children: clinical findings
      and mucosal immune response.
AB  - OBJECTIVES: Peptic ulcer disease (PUD) is highly prevalent among adults but less
      common in children. Helicobacter pylori infection, the main cause of PUD, is,
      however, acquired extremely early in life. The aim of the study was to analyze
      clinical characteristics of children with PUD in a country with a high prevalence
      of the disease and to evaluate which host factors could determine this clinical
      outcome. METHODS: Children referred for upper gastrointestinal (GI) endoscopy
      with suspicion of peptic diseases were included prospectively during an 8-year
      period. Antral biopsies were performed to determine H pylori presence and mucosal
      cytokines profile. RESULTS: A total of 307 children between 3 and 18 years old
      were enrolled. Of the total, 237 children (46% boys) with complete data were
      included. H pylori infection was confirmed in 133 (56.1%) participants. Duodenal
      ulcer (DU) was diagnosed in 32 patients (13.5%); among them 29 were infected with
      H pylori (90.6%). Infected children had a nodular appearance of the gastric
      mucosa more often than noninfected children. Noninfected children had fewer
      lymphoid follicles and less inflammatory infiltrate than infected children. Only
      mucosal polymorphonuclear cell infiltration was more intense in DU-infected
      children as compared with non-DU-infected children. DU-infected children had
      higher levels of mucosal interferon-gamma than noninfected and non-DU-infected
      patients. Non-DU-infected children had also higher levels of mucosal interleukin
      10 than noninfected patients (P < 0.05). CONCLUSIONS: PUD in children, especially
      DU, is strongly associated with H pylori infection in developing countries. There
      is no distinctive clinical presentation of children with PUD. T-helper cytokine
      balance may influence clinical outcomes in children.

PMID- 25050848
TI  - Long-term experience with ZENPEP in infants with exocrine pancreatic
      insufficiency associated with cystic fibrosis.
AB  - The objective of our study was to determine whether infants with cystic fibrosis
      who developed exocrine pancreatic insufficiency in early infancy would tolerate
      long-term treatment with ZENPEP (pancrelipase) delayed-release capsules,
      containing 3000 US Pharmacopeia units of lipase/capsule, and demonstrate
      consistent long-term growth. The most common treatment-emergent adverse events
      were diarrhea, vomiting, and constipation (mild or moderate). At study
      completion, median weight-for-age percentiles increased from 22nd to 49th, median
      length-for-age percentiles increased from 36.5th to 42nd, and median weight-for
      length percentiles increased from 41.5th to 55.5th. Long-term treatment (up to 12
      months) of infants with exocrine pancreatic insufficiency owing to cystic
      fibrosis with ZENPEP was well tolerated and associated with improved growth
      parameters. This is the first long-term study of pancreatic enzyme replacement
      therapy conducted in this patient population. 

PMID- 25050849
TI  - Metal-free oxidative olefination of primary amines with benzylic C-H bonds
      through direct deamination and C-H bond activation.
AB  - An oxidative olefination reaction between aliphatic primary amines and benzylic
      sp(3) C-H bonds has been achieved using N-bromosuccinimide as catalyst and tert
      butyl hydroperoxide as oxidant. The olefination proceeds under mild metal-free
      conditions through direct deamination and benzylic C-H bond activation, and
      provides easy access to biologically active 2-styrylquinolines with (E)
      configuration. 

PMID- 25050850
TI  - Analysis of human cytomegalovirus-encoded SUMO targets and temporal regulation of
      SUMOylation of the immediate-early proteins IE1 and IE2 during infection.
AB  - Post-translational modification of proteins by members of the small ubiquitin
      like modifier (SUMO) is involved in diverse cellular functions. Many viral
      proteins are SUMO targets and also interact with the cellular SUMOylation system.
      During human cytomegalovirus (HCMV) infection, the immediate-early (IE) proteins
      IE1 and IE2 are covalently modified by SUMO. IE2 SUMOylation promotes its
      transactivation activity, whereas the role of IE1 SUMOylation is not clear. We
      performed in silico, genome-wide analysis to identify possible SUMOylation sites
      in HCMV-encoded proteins and evaluated their modification using the E. coli
      SUMOylation system and in vitro assays. We found that only IE1 and IE2 are
      substantially modified by SUMO in E. coli, although US34A was also identified as
      a possible SUMO target in vitro. We also found that SUMOylation of IE1 and IE2 is
      temporally regulated during viral infection. Levels of SUMO-modified form of IE1
      were increased during the early phase of infection, but decreased in the late
      phase when IE2 and its SUMO-modified forms were expressed at high levels. IE2
      expression inhibited IE1 SUMOylation in cotransfection assays. As in IE2
      SUMOylation, PIAS1, a SUMO E3 ligase, interacted with IE1 and enhanced IE1
      SUMOylation. In in vitro assays, an IE2 fragment that lacked covalent and non
      covalent SUMO attachment sites, but was sufficient for PIAS1 binding, effectively
      inhibited PIAS1-mediated SUMOylation of IE1, indicating that IE2 expression
      negatively regulates IE1 SUMOylation. We also found that the IE2-mediated
      downregulation of IE1 SUMOylation correlates with the IE1 activity to repress the
      promoter containing the interferon stimulated response elements. Taken together,
      our data demonstrate that IE1 and IE2 are the main viral SUMO targets in HCMV
      infection and that temporal regulation of their SUMOylation may be important in
      the progression of this infection. 

PMID- 25050852
TI  - Does the experience of ownership over a rubber hand change body size perception
      in anorexia nervosa patients?
AB  - Anorexia nervosa (AN) patients show disturbances in body size experience. Here,
      malleability of body representation was assessed by inducing the Rubber Hand
      Illusion (RHI). Specifically the impact of the illusion on body size estimation
      was investigated. Thirty AN patients and thirty healthy females participated. The
      RHI was induced synchronously (experimental condition) and asynchronously
      (control condition) Both before and after induction of the RHI participants were
      asked to estimate the size of their own and the rubber hand. The results showed
      that AN patients had a stronger experience of ownership over the rubber hand than
      healthy females in the experimental, but not the control condition. AN patients
      and HC did not differ on proprioceptive drift. Before induction of the illusion
      AN patients overestimated hand width. After induction of the illusion
      (experimental as well as control condition) AN patients no longer overestimated
      the width of their hand. Healthy females correctly estimated hand size both
      before and after induction of the RHI. In conclusion, stronger experience of
      ownership over the rubber hand in the AN group implies a more malleable body
      representation in AN patients compared to healthy females. Changed hand size
      estimation in the AN group appears to be unrelated to the RHI, as it occurred
      under both experimental and control conditions of the illusion. Alternative
      interpretations are discussed. 

PMID- 25050851
TI  - Clinical significance of tumor necrosis factor-alpha inhibitors in the treatment
      of sciatica: a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Currently, no satisfactory treatment is available for
      sciatica caused by herniated discs and/or spinal stenosis. The objective of this
      study is to assess the value of tumor necrosis factor (TNF)-alpha inhibitors in
      the treatment of sciatica. METHODS: Without language restrictions, we searched
      PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the
      Cochrane Central Register of Controlled Trials and the China Academic Library and
      Information System. We then performed a systematic review and meta-analysis on
      the enrolled trials that met the inclusion criteria. RESULTS: Nine prospective
      randomized controlled trials (RCTs) and two before-after controlled trials
      involving 531 patients met our inclusion criteria and were included in this
      study. Our systematic assessment and meta-analysis demonstrated that in terms of
      the natural course of the disease, compared with the control condition, TNF-alpha
      inhibitors neither significantly relieved lower back and leg pain (both p > 0.05)
      nor enhanced the proportion of patients who felt overall satisfaction (global
      perceived effect (satisfaction)) or were able to return to work (return to work)
      (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow
      ups. In addition, compared with the control condition, TNF-alpha inhibitors could
      reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint;
      RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not
      decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and
      long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). CONCLUSION: The
      currently available evidence demonstrated that other than reducing the RR of
      discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF
      alpha inhibitors showed limited clinical value in the treatment of sciatica
      caused by herniated discs and/or spinal stenosis.

PMID- 25050853
TI  - Strategies influence neural activity for feedback learning across child and
      adolescent development.
AB  - Learning from feedback is an important aspect of executive functioning that shows
      profound improvements during childhood and adolescence. This is accompanied by
      neural changes in the feedback-learning network, which includes pre-supplementary
      motor area (pre- SMA)/anterior cingulate cortex (ACC), dorsolateral prefrontal
      cortex (DLPFC), superior parietal cortex (SPC), and the basal ganglia. However,
      there can be considerable differences within age ranges in performance that are
      ascribed to differences in strategy use. This is problematic for traditional
      approaches of analyzing developmental data, in which age groups are assumed to be
      homogenous in strategy use. In this study, we used latent variable models to
      investigate if underlying strategy groups could be detected for a feedback
      learning task and whether there were differences in neural activation patterns
      between strategies. In a sample of 268 participants between ages 8 to 25 years,
      we observed four underlying strategy groups, which were cut across age groups and
      varied in the optimality of executive functioning. These strategy groups also
      differed in neural activity during learning; especially the most optimal
      performing group showed more activity in DLPFC, SPC and pre-SMA/ACC compared to
      the other groups. However, age differences remained an important contributor to
      neural activation, even when correcting for strategy. These findings contribute
      to the debate of age versus performance predictors of neural development, and
      highlight the importance of studying individual differences in strategy use when
      studying development. 

PMID- 25050855
TI  - Microwave-specific acceleration of a Friedel-Crafts reaction: evidence for
      selective heating in homogeneous solution.
AB  - Thermally promoted Friedel-Crafts benzylation of arene solvents has been examined
      under both conventional convective heating with an oil bath and heating using
      microwave (MW) energy. Bulk solution temperatures-as measured by internal and
      external temperature probes and as defined by solvent reflux-were comparable in
      both sets of experiments. MW-specific rate enhancements were documented under
      certain conditions and not others. The observed rate enhancements at a given
      temperature are proposed to arise from selective MW heating of polar solutes,
      perturbing thermal equilibrium between the solute and bulk solution. Central to
      MW-specific thermal phenomena is the difference between heat and temperature.
      Temperature is a measure of the ensemble average kinetic molecular energy of all
      solution components, but temperature does not provide information about solute
      specific energy differences that may arise as a consequence of selective MW
      heating. Enhanced chemical reactivity of the MW-absorbing solute can be described
      as a MW-specific "extra-temperature thermal effect", because the measurable
      solution temperature only captures a portion of the solute kinetic molecular
      energy. Experimental factors that favor MW-specific rate enhancements are
      discussed with an eye toward future development of MW-actuated organic reactions,
      in which the observed thermal reactivity exceeds what is predicted from
      temperature-based Arrhenius calculations. 

PMID- 25050854
TI  - Different time course of visuocortical signal changes to fear-conditioned faces
      with direct or averted gaze: a ssVEP study with single-trial analysis.
AB  - Social organisms fundamentally rely on experience to successfully navigate in a
      social world by associating social stimuli with aversive versus safe qualities.
      Cognitive neuroscience research has shown that visual cues reliably paired with
      danger are processed more efficiently than neutral cues, and that such
      facilitated sensory processing extends to low levels of the visual system. The
      present study aimed at determining the extent to which visual cortical engagement
      elicited by a face stimulus with learned affective value is modulated by
      relatively subtle facial features such as gaze direction and emotional
      expression. To this end, electro-cortical processing of direct-gaze compared to
      averted-gaze faces serving as CS+ cues was investigated in a differential fear
      conditioning paradigm. Furthermore it was investigated whether gaze shift
      interacted with angry facial expressions to confer greater immunity to extinction
      of learned associations. Behavioral ratings and visually evoked steady-state
      potentials (ssVEP) were recorded in healthy human participants. As expected,
      direct-gaze CS+ compared to averted-gaze CS- cues elicited larger ssVEP
      amplitudes during conditioning, whereas this differentiation was not observed
      when averted-gaze faces were paired with the aversive US. Importantly, a more
      fine-grained analysis examining trial-by-trial changes in visual cortical
      activation across the learning phases revealed that this effect was not
      necessarily due to lack of learning per se, but mainly due to a delayed build-up
      of cortical amplification for the averted-gaze CS+ cues. This suggests that the
      temporal dynamics of cortical engagement with aversively conditioned faces vary
      as a function of the cue with gaze direction as an important modulator of the
      speed of the acquisition of the aversive response. 

PMID- 25050856
TI  - Nonlinear optical molecular switches for alkali ion identification.
AB  - This work demonstrates by means of DFT and ab initio calculations that
      recognition of alkali cations can be achieved by probing the variations of the
      second-order nonlinear optical properties along the commutation process in
      spiropyran/merocyanine systems. Due to the ability of the merocyanine isomer to
      complex metal cations, the switching between the two forms is accompanied by
      large contrasts in the quadratic hyperpolarizability that strongly depend on the
      size of the cation in presence. Exploiting the nonlinear optical responses of
      molecular switches should therefore provide powerful analytical tools for
      detecting and identifying metal cations in solution. 

PMID- 25050857
TI  - MALDI mass spectrometry imaging for the simultaneous location of resveratrol,
      pterostilbene and viniferins on grapevine leaves.
AB  - To investigate the in-situ response to a stress, grapevine leaves have been
      subjected to mass spectrometry imaging (MSI) experiments. The Matrix Assisted
      Laser Desorption/Ionisation (MALDI) approach using different matrices has been
      evaluated. Among all the tested matrices, the 2,5-dihydroxybenzoic acid (DHB) was
      found to be the most efficient matrix allowing a broader range of detected
      stilbene phytoalexins. Resveratrol, but also more toxic compounds against fungi
      such as pterostilbene and viniferins, were identified and mapped. Their spatial
      distributions on grapevine leaves irradiated by UV show their specific colocation
      around the veins. Moreover, MALDI MSI reveals that resveratrol (and piceids) and
      viniferins are not specifically located on the same area when leaves are infected
      by Plasmopara viticola. Results obtained by MALDI mass spectrometry imaging
      demonstrate that this technique would be essential to improve the level of
      knowledge concerning the role of the stilbene phytoalexins involved in a stress
      event. 

PMID- 25050858
TI  - Saponins of Trifolium spp. aerial parts as modulators of Candida albicans
      virulence attributes.
AB  - The aim was to provide the insight into the biology of C. albicans influenced by
      undescribed yet properties of saponin-rich (80%-98%) fractions (SAPFs), isolated
      from extracts of Trifolium alexandrinum, T. incarnatum, T. resupinatum var.
      resupinatum aerial parts. Their concentrations below 0.5 mg/mL were arbitrarily
      considered as subMICs for C. albicans ATCC 10231 and were further used. SAPFs
      affected yeast enzymatic activity, lowered tolerance to the oxidative stress, to
      the osmotic stress and to the action of the cell wall disrupting agent. In their
      presence, germ tubes formation was significantly and irreversibly inhibited, as
      well as Candida invasive capacity. The evaluation of SAPFs interactions with anti
      mycotics showed synergistic activity, mainly with azoles. Fluconazole MIC was
      lowered-susceptible C. albicans ATCC 10231 was more susceptible, and resistant C.
      glabrata (clinical strain) become more susceptible (eightfold). Moreover, the
      tested samples showed no hemolytic activity and at the concentrations up to 0.5
      mg/mL did not reduce viability of fibroblasts L929. This study provided the
      original evidence that SAPFs of Trifolium spp. aerial part exhibit significant
      antimicrobial activity, by reduce the expression/quantity of important Candida
      virulence factors and have good potential for the development of novel antifungal
      products supporting classic drugs. 

PMID- 25050859
TI  - Expression analysis and biological activity of moronecidin from rock bream,
      Oplegnathus fasciatus.
AB  - The piscidin-family, one of antimicrobial peptides (AMPs) mainly distributed in
      fish, is crucial effectors of fish innate immune response. Piscidin-family
      typically has broad-spectrum antimicrobial activity and the ability to modulate
      the immune response. In this study, we identified moronecidin (Rbmoro) included
      in piscidin-family from rock bream and investigated its gene expression using
      quantitative real-time PCR and biological activity (including antimicrobial and
      cytotoxic activity). The coding region of Rbmoro was 204 bp encoding 67 amino
      acid residues. Tertiary structure prediction of Rbmoro showed an amphipathic
      alpha-helical structure. Rbmoro gene was widely expressed in different tissues of
      healthy fish. Additionally, Rbmoro gene expression was induced in all tested
      tissues after infection with Edwardsiella tarda, Streptococcus iniae and red
      seabream iridovirus. We synthesized mature peptide of Rbmoro based on amino acid
      sequence of its AMP 12 domain, and the synthetic peptide appeared broad-spectrum
      antimicrobial activity to various bacteria. However, the synthetic peptide has
      weak haemolytic activity against fish erythrocytes. These results suggest that
      Rbmoro might play an important role in innate immune response of rock bream.

PMID- 25050860
TI  - Accurate quantitation of MHC-bound peptides by application of isotopically
      labeled peptide MHC complexes.
AB  - Knowledge of the accurate copy number of HLA class I presented ligands is
      important in fundamental and clinical immunology. Currently, the best copy number
      determinations are based on mass spectrometry, employing single reaction
      monitoring (SRM) in combination with a known amount of isotopically labeled
      peptide. The major drawback of this approach is that the losses during sample
      pretreatment, i.e. immunopurification and filtration steps, are not well defined
      and must, therefore, be estimated. In addition, such losses can vary for
      individual peptides. Therefore, we developed a new approach in which isotopically
      labeled peptide-MHC monomers (hpMHC) are prepared and added directly after cell
      lysis, i.e. before the usual sample processing. Using this approach, all losses
      during sample processing can be accounted for and allows accurate determination
      of specific MHC class I-presented ligands. Our study pinpoints the
      immunopurification step as the origin of the rather extreme losses during sample
      pretreatment and offers a solution to account for these losses. Obviously, this
      has important implications for accurate HLA-ligand quantitation. The strategy
      presented here can be used to obtain a reliable view of epitope copy number and
      thus allows improvement of vaccine design and strategies for immunotherapy.

PMID- 25050861
TI  - Directed differentiation of patient-specific induced pluripotent stem cells
      identifies the transcriptional repression and epigenetic modification of NKX2-5,
      HAND1, and NOTCH1 in hypoplastic left heart syndrome.
AB  - The genetic basis of hypoplastic left heart syndrome (HLHS) remains unknown, and
      the lack of animal models to reconstitute the cardiac maldevelopment has hampered
      the study of this disease. This study investigated the altered control of
      transcriptional and epigenetic programs that may affect the development of HLHS
      by using disease-specific induced pluripotent stem (iPS) cells. Cardiac
      progenitor cells (CPCs) were isolated from patients with congenital heart
      diseases to generate patient-specific iPS cells. Comparative gene expression
      analysis of HLHS- and biventricle (BV) heart-derived iPS cells was performed to
      dissect the complex genetic circuits that may promote the disease phenotype. Both
      HLHS- and BV heart-derived CPCs were reprogrammed to generate disease-specific
      iPS cells, which showed characteristic human embryonic stem cell signatures,
      expressed pluripotency markers, and could give rise to cardiomyocytes. However,
      HLHS-iPS cells exhibited lower cardiomyogenic differentiation potential than BV
      iPS cells. Quantitative gene expression analysis demonstrated that HLHS-derived
      iPS cells showed transcriptional repression of NKX2-5, reduced levels of TBX2 and
      NOTCH/HEY signaling, and inhibited HAND1/2 transcripts compared with control
      cells. Although both HLHS-derived CPCs and iPS cells showed reduced SRE and TNNT2
      transcriptional activation compared with BV-derived cells, co-transfection of
      NKX2-5, HAND1, and NOTCH1 into HLHS-derived cells resulted in synergistic
      restoration of these promoters activation. Notably, gain- and loss-of-function
      studies revealed that NKX2-5 had a predominant impact on NPPA transcriptional
      activation. Moreover, differentiated HLHS-derived iPS cells showed reduced H3K4
      dimethylation as well as histone H3 acetylation but increased H3K27
      trimethylation to inhibit transcriptional activation on the NKX2-5 promoter.
      These findings suggest that patient-specific iPS cells may provide molecular
      insights into complex transcriptional and epigenetic mechanisms, at least in
      part, through combinatorial expression of NKX2-5, HAND1, and NOTCH1 that
      coordinately contribute to cardiac malformations in HLHS. 

PMID- 25050863
TI  - Role of imaging in the diagnosis of diffuse and interstitial lung diseases.
AB  - PURPOSE OF REVIEW: This review aims to provide a literature update focused on the
      role of imaging in the diagnosis, prognosis and quantification of interstitial
      lung diseases (ILDs). Special emphasis is given in the management of atypical
      cases and in the multidisciplinary team approach in reaching the diagnosis of the
      various ILDs. RECENT FINDINGS: Accumulated knowledge on imaging has increased the
      accuracy of differential diagnosis in atypical cases, in overlap of findings and
      in secondary as opposed to idiopathic ILDs. There is increasing awareness about
      interstitial lung abnormalities in smokers' lungs from lung cancer screening and
      indirect evidence of linkage of fibrosis and smoking. Improvement in radiologic
      pathologic correlation reveals less typical high-resolution computed tomography
      patterns to be predictive of pulmonary fibrosis. Major diagnostic criteria such
      as honeycombing may be hampered by the coexistence of emphysema. High-resolution
      computed tomography may predict clinical outcome and survival of patients in ILDs
      and is a decision maker in the multidisciplinary approach of diagnosis. SUMMARY:
      High-resolution computed tomography plays a crucial role in the diagnosis,
      prognosis, quantification and monitoring of ILDs. It provides a definite
      noninvasive diagnosis in typical findings and helps in reaching the most accurate
      diagnosis in a multidisciplinary discussion in equivocal cases.

PMID- 25050862
TI  - Etravirine and rilpivirine-specific mutations selected by efavirenz and
      nevirapine exposure in patients infected with HIV-1 non-B subtypes.

PMID- 25050864
TI  - Antioxidant effect of rosemary (Rosmarinus officinalis L.) extract in soybean
      lecithin-based semen extender following freeze-thawing process of ram sperm.
AB  - The aim of current study was to evaluate effect of rosemary aqueous extract on
      post-thawed ram sperm quality in a soybean lecithin-based (SL) extender. Ram
      semen samples were obtained, extended with SL extender and supplemented with 0%
      (SL-R0), 2% (SL-R2), 4% (SL-R4), 6% (SL-R6), and 8% (SL-R8) rosemary aqueous
      extract. Following equilibration, the straws were frozen, and then plunged into
      the liquid nitrogen. After thawing, sperm motility and velocity parameters,
      plasma membrane functionality, viability, acrosomal and capacitation status were
      evaluated. Membrane lipid peroxidation was also analyzed through the
      malondialdehyde (MDA) concentration. Our results showed that SL-R4 and SL-R6
      groups resulted in higher (p < 0.05) percentages of total motility, progressive
      motility, and plasma membrane functionality, as compared with other groups.
      Highest (p < 0.05) viable and lowest (p < 0.05) dead spermatozoa were observed in
      SL-R6 group compared to the other groups. The acrosomal and capacitation status
      were not affected (p > 0.05) by different levels of rosemary aqueous extract.
      Lower (p < 0.05) MDA concentration has been observed in SL-R4 and SL-R6 groups.
      The results of this study demonstrate that supplementation of SL extender with
      rosemary aqueous extract influences post-thawed ram sperm quality in a dose
      dependent manner.

PMID- 25050865
TI  - Cation exchange in a 3D perovskite-synthesis of Ni(0.5)TaO3.
AB  - Reaction of NiCl2 with NaTaO3 leads the formation of the perovskite phase
      Ni(0.5)TaO3, via a topochemical nickel-for-sodium cation exchange in which the
      framework of apex-linked TaO6 octahedra present in the parent phase is retained.
      Neutron powder diffraction data indicate Ni(0.5)TaO3 adopts a structure analogous
      to the paraelectric phase of LiTaO3, with triclinic P1 crystallographic symmetry.
      Although Ni(0.5)TaO3 has features which make it a good candidate phase for
      magnetoelectric multiferroic behavior, the phase remains paramagnetic in the
      temperature range 15 < T (K) < 300, and detailed crystallographic
      characterization and analysis of SHG activity indicate it retains a
      centrosymmetric structure down to the lowest temperatures measured (5 K).
      Topochemical cation exchange reactions of 3D perovskite oxides offer the
      opportunity to prepare a wide range of novel metastable phases in a rational
      manner with a high degree of synthetic control.

PMID- 25050868
TI  - Photoreduction and stabilization capability of molecular weight fractionated
      natural organic matter in transformation of silver ion to metallic nanoparticle.
AB  - Photoinduced reduction of silver ion (Ag(+)) to silver nanoparticles (AgNPs) by
      dissolved organic matter (DOM) plays a crucial role in the transformation and
      transport of engineered AgNPs and Ag(+) in aquatic environments. DOM is a mixture
      of natural polymers with wide molecular weight (MW) distribution, and the roles
      of specific components of DOM in the photoreduction of Ag(+) to AgNPs are still
      not understood. In this study, MW fractionated natural organic matter (Mf-NOM)
      were investigated for their roles on the photoreduction process and stabilization
      of the formed AgNPs. This photoinduced reduction process depends highly on pH,
      concentration of Ag(+) and NOM, light quality, and the MW of Mf-NOM.
      Monochromatic radiation and light attenuation correction suggested that the
      difference of Mf-NOM on reduction was mainly ascribed to the differential light
      attenuation of Mf-NOM rather than the "real" reductive ability. More importantly,
      compared with low MW fractions, the high MW Mf-NOMs exhibit drastically higher
      capability in stabilizing the photosynthesized AgNPs against Ca(2+)-induced
      aggregation. This finding is important for a better understanding of the
      differential roles of Mf-NOM in the transformation and transport of Ag(+) and
      engineered AgNPs in DOM-rich surface water. 

PMID- 25050866
TI  - Sedation agents differentially modulate cortical and subcortical blood
      oxygenation: evidence from ultra-high field MRI at 17.2 T.
AB  - BACKGROUND: Sedation agents affect brain hemodynamic and metabolism leading to
      specific modifications of the cerebral blood oxygenation level. We previously
      demonstrated that ultra-high field (UHF) MRI detects changes in cortical blood
      oxygenation following the administration of sedation drugs commonly used in
      animal research. Here we applied the UHF-MRI method to study clinically relevant
      sedation drugs for their effects on cortical and subcortical (thalamus, striatum)
      oxygenation levels. METHODS: We acquired T2*-weighted images of Sprague-Dawley
      rat brains at 17.2T in vivo. During each MRI session, rats were first
      anesthetized with isoflurane, then with a second sedative agent (sevoflurane,
      propofol, midazolam, medetomidine or ketamine-xylazine) after stopping
      isoflurane. We computed a T2*-oxygenation-ratio that aimed at estimating cerebral
      blood oxygenation level for each sedative agent in each region of interest:
      cortex, hippocampus, thalamus and striatum. RESULTS: The T2*-oxygenation-ratio
      was consistent across scan sessions. This ratio was higher with inhalational
      agents than with intravenous agents. Under sevoflurane and medetomidine, T2*
      oxygenation-ratio was homogenous across the brain regions. Intravenous agents
      (except medetomidine) induced a T2*-oxygenation-ratio imbalance between cortex
      and subcortical regions: T2*-oxygenation-ratio was higher in the cortex than the
      subcortical areas under ketamine-xylazine; T2*-oxygenation-ratio was higher in
      subcortical regions than in the cortex under propofol or midazolam. CONCLUSION:
      Preclinical UHF MRI is a powerful method to monitor the changes in cerebral blood
      oxygenation level induced by sedative agents across brain structures. This
      approach also allows for a classification of sedative agents based on their
      differential effects on cerebral blood oxygenation level.

PMID- 25050869
TI  - The effects of calcium channel blockers on nephropathy and pigment epithelium
      derived factor in the treatment of hypertensive patients with type 2 diabetes
      mellitus.
AB  - The aim of this study was to compare the effects of a dihidropiridin calcium
      channel blocker amlodipin and a non-dihidropiridin calcium channel blocker
      verapamil on nephropathy and serum pigment epithelium-derived factor (PEDF)
      levels of type 2 diabetic patients with hypertension. Forty-one type 2 diabetic
      patients with uncontrolled hypertension in spite of using angiotensin-converting
      enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) were
      enrolled in the study. The patients were randomized in two groups. First group
      received amlodipin (5-10 mg/d) and second group verapamil (120-240 mg/d) for 6
      weeks. The difference between two calcium channel blocker treatments was
      investigated by analyzing urinary albumin excretion and plasma PEDF levels of
      patients at the end of 6 weeks. Urinary microalbumin/creatinine values were
      decreased in both amlodipin and verapamil groups but it was not statistically
      significant. Plasma PEDF levels also decreased significantly in both groups at
      the end of the treatment (p < 0.001 and p < 0.001, respectively). At the end of
      the treatment there was no significant difference between changes in values of
      systolic BP, diastolic BP, microalbumin/creatinine and PEDF percentage in both
      groups (p = 0.788, p = 0.926, p = 0.908, p = 0.140, respectively). PEDF values
      showed a positive correlation with microalbumin/creatinine, hb A1c, FBS, systolic
      and diastolic BP levels. It was observed that both of the drugs have similar
      effects on nefhropathy and PEDF at the end of the treatment. In this study, we
      suggest that calcium channel blockers may have renoprotective effects by
      different mechanisms except their antihypertensive effects and this may be
      important to determine the selection of antihypertensive drug combinations in
      diabetic nephropathy.

PMID- 25050871
TI  - Theoretical study of the temperature dependence of the vibrational relaxation of
      the H2O bend fundamental in liquid water and the subsequent distortion of the
      hydrogen bond network.
AB  - The molecular dynamics with quantum transitions method is used to study the
      temperature dependence of the relaxation dynamics of the H2O bend fundamental in
      liquid water in the range from 277 to 348 K and the subsequent variation of the
      hydrogen bonds network in the liquid. The vibrational bending degrees of freedom
      of the water molecules are all described by quantum mechanics while the remaining
      translational and rotational motions are described classically. The participation
      of the H-bonds in the relaxation process is studied taking into account the
      dependence of the relaxation lifetimes on the number of H-bonds formed by the
      initially excited water molecule and the amount of energy transferred into the
      hindered rotational motions. It is found that the intermolecular vibrational
      energy transfer plays an important role in the relaxation mechanism, with almost
      no temperature dependence, and that the energy transfer into the rotational
      degrees of freedom is favored over the energy transfer into the translational
      motions. The thermalization of the system after relaxation is completed in a time
      scale shorter than the time taken for the H-bond network to recover. The
      relaxation and equilibration times calculated compare well with experimental and
      previous theoretical results. 

PMID- 25050870
TI  - Functional and molecular characterization of hyposensitive underactive bladder
      tissue and urine in streptozotocin-induced diabetic rat.
AB  - BACKGROUND: The functional and molecular alterations of nerve growth factor (NGF)
      and Prostaglandin E2 (PGE2) and its receptors were studied in bladder and urine
      in streptozotocin (STZ)-induced diabetic rats. METHODOLOGY/PRINCIPAL FINDINGS:
      Diabetes mellitus was induced with a single dose of 45 mg/kg STZ
      Intraperitoneally (i.p) in female Sprague-Dawley rats. Continuous cystometrogram
      were performed on control rats and STZ treated rats at week 4 or 12 under
      urethane anesthesia. Bladder was then harvested for histology, expression of EP
      receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of
      apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all
      groups for urine levels of PGE2, and NGF assay. DM induced progressive increase
      of bladder weight, urine production, intercontraction interval (ICI) and residual
      urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP)1
      and EP3 receptors and downregulation of NGF expression, increase in urine NGF and
      decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by
      intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM
      group at week 12. CONCLUSIONS/SIGNIFICANCE: DM induced hyposensitive underactive
      bladder which is characterized by increased inflammatory reaction, apoptosis,
      urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF
      and urine PGE2. The data suggest that EP3 receptor are potential targets in the
      treatment of diabetes induced underactive bladder.

PMID- 25050873
TI  - The production of isoflavonoids in Genista tinctoria L. cell suspension culture
      after abiotic stressors treatment.
AB  - The increased content of isoflavonoids in dry cell suspension and nutrient medium
      was observed after application of electric current and AgNO3 on Genista tinctoria
      L. cultures in vitro. The highest content of genistin (1.7 mg g(- 1) DW - dry
      weight) was measured in the dry cell suspension culture after 30 min elicitation
      of 10 V and 6 h cultivation and daidzein content (3.5 mg g(- 1) DW) was measured
      after 60 min elicitation of 5 V and 24 h cultivation. In the case of AgNO3
      elicitation, the content of genistin in dry cell suspension culture (0.5 mg g(-
      1) DW) was highest after 48 h of AgNO3 treatment and concentration of 5.9 * 10(-
      4) mol/L. The AgNO3 concentration of 5.9 * 10(- 4) mol/L was also the most
      effective combination for daidzein production (0.9 mg g(- 1) DW) after 168 h. The
      results of this study show that the secondary metabolites could also be released
      from G. tinctoria L. cells into the nutrient medium. 

PMID- 25050872
TI  - A cognitive-existential intervention to improve existential and global quality of
      life in cancer patients: A pilot study.
AB  - OBJECTIVE: We developed a specific cognitive-existential intervention to improve
      existential distress in nonmetastatic cancer patients. The present study reports
      the feasibility of implementing and evaluating this intervention, which involved
      12 weekly sessions in both individual and group formats, and explores the
      efficacy of the intervention on existential and global quality of life (QoL)
      measures. METHOD: Some 33 nonmetastatic cancer patients were randomized between
      the group intervention, the individual intervention, and the usual condition of
      care. Evaluation of the intervention on the existential and global QoL of
      patients was performed using the existential well-being subscale and the global
      scale of the McGill Quality of Life (MQoL) Questionnaire. RESULTS: All
      participants agreed that their participation in the program helped them deal with
      their illness and their personal life. Some 88.9% of participants agreed that
      this program should be proposed for all cancer patients, and 94.5% agreed that
      this intervention helped them to reflect on the meaning of their life. At post
      intervention, both existential and psychological QoL improved in the group
      intervention versus usual care (p = 0.086 and 0.077, respectively). At the three
      month follow-up, global and psychological QoL improved in the individual
      intervention versus usual care (p = 0.056 and 0.047, respectively). SIGNIFICANCE
      OF RESULTS: This pilot study confirms the relevance of the intervention and the
      feasibility of the recruitment and randomization processes. The data strongly
      suggest a potential efficacy of the intervention for existential and global
      quality of life, which will have to be confirmed in a larger study.

PMID- 25050874
TI  - Complete mitochondrial genome of Ark shell Scapharca subcrenata.
AB  - Complete mitochondrial genome of Scapharca subcrenata was determined in this
      report. It is 48,161 bp in length, being the largest mitochondrial genome among
      reported shellfish at present. The entire mitochondrial genome consists of 57
      genes including 12 protein-coding genes, 2 ribosomal RNAs and 41 transfer RNAs. 

PMID- 25050875
TI  - The complete mitochondrial genome of the fire coral-inhabiting barnacle
      Megabalanus ajax (Sessilia: Balanidae): gene rearrangements and atypical gene
      content.
AB  - The complete mitochondrial genome of Megabalanus ajax Darwin, 1854 (Sessilia:
      Balanidae) is reported. Compared to typical gene content of metazoan
      mitochondrial genomes, duplication of one tRNA gene (trnL2) and absence of
      another tRNA gene (trnS1) are identified in M. ajax mitochondrial genome. There
      is a replacement of one tRNA (trnS1) by another tRNA (trnL2) in M. ajax
      mitochondrial genome compared to Megabalanus volcano mitochondrial genome.
      Inversion of a six-gene block (trnP-nd4L-nd4-trnH-nd5-trnF) is found between M.
      ajax/M. volcano and Tetraclita japonica mitochondrial genomes. With reference to
      the pancrustacean mitochondrial ground pattern, there is an inversion of a large
      gene block from the light strand to heavy strand in the two Megabalanus
      mitochondrial genomes, including three PCGs and two tRNAs (nd4L-nd4-trnH-nd5
      trnF). Furthermore, four tRNAs (trnA, trnE, trnQ and trnC) exhibit translocation,
      while translocation and inversion occur in three tRNAs (trnP, trnY and trnK). 

PMID- 25050876
TI  - Enhancing analysis of cells and proteins by fluorescence imaging on silk-based
      biomaterials: modulating the autofluorescence of silk.
AB  - Silk is a versatile and established biomaterial for various tissue engineering
      purposes. However, it also exhibits strong autofluorescence signals-thereby
      hindering fluorescence imaging analysis of cells and proteins on silk-derived
      biomaterials. Sudan Black B (SB) is a lysochrome dye commonly used to stain
      lipids in histology. It has also been reported to be able to quench
      autofluorescence of tissues in histology and has been tested on artificial
      biomedical polymers in recent years. It was hypothesized that SB would exert
      similar quenching effects on silk, modulating the autofluorescence signals, and
      thereby enabling improved imaging analysis of cells and molecules of interests.
      The quenching effect of SB on the intrinsic fluorescence properties of silk and
      on commercial fluorescent dyes were first investigated in this study. SB was then
      incorporated into typical fluorescence-based staining protocols to study its
      effectiveness in improving fluorescence-based imaging of the cells and proteins
      residing with the silk-based biomaterials. Silk processed into various forms of
      biomaterials (e.g., films, sponges, fibers, and electrospun mats) was seeded with
      cells and cultured in vitro. At sacrificial time points, specimens were
      harvested, fixed, and prepared for fluorescence staining. SB, available
      commercially as a powder, was dissolved in 70% ethanol (0.3% [w/v]) to form
      staining solutions. SB treatment was introduced at the last step of typical
      immunofluorescence staining protocols for 15-120 min. For actin staining
      protocols by phalloidin toxin, SB staining solutions were added before and after
      permeabilization with Triton-X for 15-30 min. Results showed that ideal SB
      treatment duration is about 15 min. Apart from being able to suppress the
      autofluorescence of silk, this treatment duration was also not too long to
      adversely affect the fluorescent labeling probes used. The relative improvement
      brought about by SB treatment was most evident in the blue and green emission
      wavelengths compared with the red emission wavelength. This study has showed that
      the use of SB is a cost and time effective approach to enhance fluorescence-based
      imaging analyses of cell-seeded silk biomaterials, which otherwise would have
      been hindered by the unmodulated autofluorescence signals. 

PMID- 25050877
TI  - The use of the bispectral index in the detection of pain in mechanically
      ventilated adults in the intensive care unit: a review of the literature.
AB  - BACKGROUND: Pain assessment is an immense challenge for clinicians, especially in
      the context of the intensive care unit, where the patient is often unable to
      communicate verbally. Several methods of pain assessment have been proposed to
      assess pain in this environment. These include both behavioural observation
      scales and evaluation of physiological measurements such as heart rate and blood
      pressure. Although numerous validation studies pertaining to behavioural
      observation scales have been published, several limitations associated with using
      these measures for pain assessment remain. Over the past few years, researchers
      have been interested in the use of the bispectral index monitoring system as a
      proxy for the evaluation of encephalography readings to assess the level of
      anesthesia and, potentially, analgesia. OBJECTIVES: To synthesize the main
      studies exploring the use of the bispectral index monitoring system for pain
      assessment, to guide future research in adults under sedation in the intensive
      care unit. METHOD: The EMBASE, Medline, CINAHL and PsycINFO databases were
      searched for studies published between 1996 and 2013 that evaluated the use of
      the bispectral index in assessing pain. RESULTS: Most studies conclude that
      nociceptive stimulation causes a significant increase in the bispectral index and
      revealed the importance of controlling certain confounding variables such as the
      level of sedation. DISCUSSION: Further studies are needed to clearly demonstrate
      the relationship between nociceptive stimuli and the bispectral index, as well as
      the specificity of the bispectral index in detecting pain.

PMID- 25050878
TI  - Discovery of nanomolar phosphoinositide 3-kinase gamma (PI3Kgamma) inhibitors
      using ligand-based modeling and virtual screening followed by in vitro analysis.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) is member of a family of enzymes
      involved in cancer pathogenesis. Accordingly, considerable efforts have been
      carried out to develop new PI3Kgamma inhibitors. Towards this end we explored the
      pharmacophoric space of PI3Kgamma using three diverse sets of inhibitors.
      Subsequently, we employed genetic algorithm-based QSAR analysis to select optimal
      combination of pharmacophoric models and physicochemical descriptors that can
      explain bioactivity variation within training inhibitors. Interestingly, two
      successful pharmacophores were selected within two statistically consistent QSAR
      models. The close similarity among the two binding models prompted us to merge
      them in a hybrid pharmacophore. The resulting model showed superior receiver
      operator characteristic curve (ROC) and closely resembled binding interactions
      seen in crystallographic ligand-PI3Kgamma complexes. The resulting model was
      employed to screen the national cancer institute (NCI) list of compounds to
      search for new PI3Kgamma ligands. After testing captured hits in vitro, 19
      compounds showed nanomolar IC50 values against PI3Kgamma. The chemical structures
      and purities of most potent hits were validated using NMR and MS experiments.

PMID- 25050879
TI  - Novel quinazoline-urea analogues as modulators for Abeta-induced mitochondrial
      dysfunction: design, synthesis, and molecular docking study.
AB  - A novel series of twenty-six quinazoline-urea derivatives was designed and
      synthesized. Their blocking activities against beta-amyloid peptide (Abeta)
      induced mitochondrial permeability transition pore (mPTP) opening were evaluated
      by JC-1 assay which measured the change of mitochondrial membrane potential.
      Seven compounds showed better inhibitory activities than the standard Cyclosporin
      A (CsA). The most active analogues were tested by MTT assay to evaluate their
      toxicity on the cellular survival; they revealed excellent cellular viability. To
      explain the difference in inhibitory activity, molecular docking study using
      (GOLD) program was performed for selected sets of the most active and inactive
      compounds on cyclophilin D (CypD) receptor as a major component of mPTP.
      Moreover, ADME profiling, in silico toxicity, drug-likeness, and drug-score
      studies were discussed. From these results, we report compound 31 as the most
      active nonpeptidyl mPTP blocker possessing quinazoline-urea scaffold; 2 folds of
      CsA activity, which would constitute a new direction for the design of novel mPTP
      modulators. 

PMID- 25050881
TI  - Design, synthesis, antimicrobial evaluation and molecular docking studies of some
      new thiophene, pyrazole and pyridone derivatives bearing sulfisoxazole moiety.
AB  - Development of new antimicrobial agents is a good solution to overcome drug
      resistance problems. In this context, new functionalized thiophene, acrylamide,
      arylhydrazone, pyrazole and pyridone derivatives bearing sulfisoxazole moiety
      were designed, synthesized and evaluated for their in vitro antibacterial and
      antifungal activities. Among the synthesized compounds, thiophene 4d and 6
      thioglucosylpyridone 17 displayed significant antibacterial activities against
      Escherichia coli (MIC, 0.007 MUg/mL vs gentamycin 1.95 MUg/mL) and Bacillis
      subtilis (MIC, 0.007 MUg/mL vs ampicillin 0.24 MUg/mL), respectively. Whereas,
      the pyrazole 6 showed the highest antifungal activity against Aspergillus
      fumigates (MIC, 0.03 MUg/mL vs amphotericin B 0.12 MUg/mL). In general, most of
      the synthesized compounds exhibited better antimicrobial activities than
      sulfisoxazole; this might be attributed to the synergistic effect of the
      sulfonamide and attached heterocyclic moieties as well as the increased
      lipophilic characters of the synthesized compounds. Molecular docking studies
      indicated that the synthesized compounds could occupy both p-amino benzoic acid
      (PABA) and pterin binding pockets of the dihydropteroate synthase (DHPS),
      suggesting that the target compounds could act by the inhibition of microbial
      DHPS enzyme. The results provide important information for the future design of
      more potent antimicrobial agents.

PMID- 25050880
TI  - Novel 9'-substituted-noscapines: synthesis with Suzuki cross-coupling, structure
      elucidation and biological evaluation.
AB  - Tubulin is a major molecular target for anticancer drugs. The dynamic process of
      microtubule assembly and disassembly can be blocked by various agents that bind
      to distinct sites on tubulin, usually its beta-subunit. Among the antimitotic
      agents that perturb microtubule dynamics, noscapinoids represent an emerging
      class of agents. In particular, 9'-bromonoscapine (EM011) has been identified as
      a potent noscapine analog. Here we present high yielding, efficient synthetic
      methods based on Suzuki coupling of 9'-alkyl and 9'-arylnoscapines and an
      evaluation of their antiproliferative properties. Our results showed that 9'
      alkyl and 9'-aryl derivatives inhibit proliferation of human cancer cells. The
      most active compounds were the 9'-methyl and the 9'-phenyl derivatives, which
      showed similar cytotoxic potency in comparison to the 9'-brominated derivative.
      Interestingly these newly synthesized derivatives did not induce cell death in
      normal human lymphocytes, suggesting that the compounds may be selective against
      cancer cells. All of these derivatives, except 9'-(2-methoxyphenyl)-noscapine,
      efficiently induced a cell cycle arrest in the G2/M phase of the cell cycle in
      HeLa and Jurkat cells. Furthermore, we showed that the most active compounds in
      HeLa cells induced apoptosis following the mitochondrial pathway with the
      activation of both caspase-9 and caspase-3. In addition, these compounds
      significantly reduced the expression of the anti-apoptotic proteins Mcl-1 and Bcl
      2. 

PMID- 25050882
TI  - Natural product-based design, synthesis and biological evaluation of anthra[2,1
      d]thiazole-6,11-dione derivatives from rhein as novel antitumour agents.
AB  - Two series of novel 2-substituted 5,7-dihydroxyanthra[2,1-d]thiazole-6,11-dione
      derivatives from natural rhein were designed, synthesized and evaluated for their
      antitumour activities against human cancer cell lines A549 and HeLa in vitro.

PMID- 25050883
TI  - FCGR3A 158V/F polymorphism and response to frontline R-CHOP therapy in diffuse
      large B-cell lymphoma.
AB  - The influence of Fc gamma receptor IIIA (FCGR3A) 158V/F polymorphisms on the
      response to rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine,
      prednisone; R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is
      uncertain. Thus, a retrospective study and a meta-analysis were performed to
      examine the possible correlation between FCGR3A 158V/F polymorphism and the
      response rate of R-CHOP regimen in patients with newly diagnosed DLBCL. The
      genotypes of FCGR3A 158V/F in 164 newly diagnosed DLBCL patients treated with R
      CHOP were determined in this retrospective study. Additionally, a meta-analysis
      of current and previously published studies was conducted. Overall response rate
      (complete and partial response, ORR) and complete response rate (CR) were
      evaluated. The results of our retrospective study showed lack of correlation
      between FCGR3A 158V/F polymorphism and ORR (p=0.78) or CR (p=0.76) with R-CHOP
      therapy. A meta-analysis of 731 cases also showed lack of significant association
      of ORR and CR in all genetic models with FCGR3A 158V/F polymorphism. In survival
      analysis, the homozygous F genotype correlated with a shorter progression-free
      survival than that of non-F/F genotype (p=0.05), this was significant for the non
      GC subset of DLBCL (p=0.04), but no association was found between overall
      survival and FCGR3A 158V/F polymorphism. Further analysis with nonsuperiority
      test (p<0.0001) suggested that FCGR3A 158V/F polymorphism was not associated with
      better ORR or CR in newly diagnosed DLBCL patient treated with R-CHOP. No clear
      relationship was found between FCGR3A 158V/F polymorphism and response to
      frontline R-CHOP therapy in patients with DLBCL. 

PMID- 25050884
TI  - Intrafamilial aggregation and heritability of office-day blood pressure
      difference in a community of African ancestry: implications for genetic
      association studies.
AB  - OBJECTIVE: An inability to show consistent relationships between gene variants
      and blood pressure (BP) may be confounded by the use of office BP measurement.
      Whether the difference between office BP and day BP (office-day) is genetically
      predetermined is unknown. We therefore aimed to determine the intrafamilial
      aggregation and heritability of office-day BP. PATIENTS AND METHODS: Nurse
      derived office BP (mean of 5 measurements according to guidelines) and 24-h
      ambulatory BP were determined for 592 participants from 198 families (67 spouse
      pairs, 361 parent-child pairs, and 169 sibling-sibling pairs), with 12 families
      having three generations, from an urban developing community of black Africans.
      Heritability estimates were determined using SAGE software. RESULTS: With
      adjustments for confounders, office systolic BP (SBP) (h=0.35+/-0.09, P<0.0001)
      showed comparable heritability estimates to 24-h SBP (h=0.33+/-0.09, P<0.0001).
      Similarly, with adjustments for confounders, office diastolic BP (DBP) (h=0.37+/
      0.09, P<0.0001) showed comparable heritability estimates as 24-h DBP (h=0.35+/
      0.09, P<0.0001). However, multivariate adjusted heritability estimates of day SBP
      (h=0.29+/-0.09, P<0.0001) and DBP (h=0.33+/-0.09, P<0.0001) were not diminished
      by further adjustments for office SBP (h=0.42+/-0.09, P<0.0001) or DBP (h=0.34+/
      0.09, P<0.0001). Further, independent of confounders, office-day BP showed
      significant intrafamilial aggregation and heritability (SBP: h=0.51+/-0.10,
      P<0.0001; DBP: h=0.37+/-0.09, P<0.0001), effects that persisted with further
      adjustments for office, day, or day-night BP (P<0.0005 for SBP and DBP).
      CONCLUSION: Although office and ambulatory BP may show similar heritability
      estimates, genetic associations with carefully determined office BP measurements
      may be confounded by the heritability of office-day BP differences.

PMID- 25050885
TI  - A genetic pedigree analysis to identify gene mutations involved in femoral head
      necrosis.
AB  - The present study presents results from a linkage and mutation screening analysis
      aiming to identify the causative gene of femoral head necrosis, also known as
      osteonecrosis of femoral head (ONFH), in a Chinese pedigree. We collected
      clinical data on the osteonecrosis pedigree, and extracted blood and genomic DNA
      from the family members. Polymerase chain reaction (PCR) and direct sequencing
      allowed to identify a mutation in the COL2A1 gene of the proband; the clinical
      manifestations of the proband meet the criteria for osteonecrosis. The exons of
      COL2A1 were amplified by polymerase chain reaction and mutation screening was
      conducted by direct sequencing in all the family members. The locus was also
      sequenced in 50 unrelated healthy controls. The c.3665G>A heterozygous mutation
      was detected in patients of the pedigree, but not in healthy individuals. We
      conclude that a mutation in the COL2A1 gene is the causative agent of ONFH in
      this family. Therefore, this mutation may be associated with osteonecrosis in
      Chinese populations. 

PMID- 25050886
TI  - Combining aesthetic with ecological values for landscape sustainability.
AB  - Humans receive multiple benefits from various landscapes that foster ecological
      services and aesthetic attractiveness. In this study, a hybrid framework was
      proposed to evaluate ecological and aesthetic values of five landscape types in
      Houguanhu Region of central China. Data from the public aesthetic survey and
      professional ecological assessment were converted into a two-dimensional
      coordinate system and distribution maps of landscape values. Results showed that
      natural landscapes (i.e. water body and forest) contributed positively more to
      both aesthetic and ecological values than semi-natural and human-dominated
      landscapes (i.e. farmland and non-ecological land). The distribution maps of
      landscape values indicated that the aesthetic, ecological and integrated
      landscape values were significantly associated with landscape attributes and
      human activity intensity. To combine aesthetic preferences with ecological
      services, the methods (i.e. field survey, landscape value coefficients,
      normalized method, a two-dimensional coordinate system, and landscape value
      distribution maps) were employed in landscape assessment. Our results could
      facilitate to identify the underlying structure-function-value chain, and also
      improve the understanding of multiple functions in landscape planning. The
      situation context could also be emphasized to bring ecological and aesthetic
      goals into better alignment. 

PMID- 25050887
TI  - Hypocretin (orexin) neuromodulation of stress and reward pathways.
AB  - Hypocretin (also known as orexin) is a peptide neuromodulator that is expressed
      exclusively in the lateral hypothalamic area and plays a fundamental role in
      wakefulness and arousal. Chronic stress and compulsive drug-seeking are two
      examples of dysregulated states of hyperarousal that are influenced by hypocretin
      transmission throughout hypothalamic, extended amygdala, brainstem, and
      mesolimbic pathways. Here, we review current advances in the understanding of
      hypocretin's modulatory actions underlying conditions of negative and positive
      emotional valence, focusing particularly on mechanisms that facilitate adaptive
      (and maladaptive) responses to stressful or rewarding environmental stimuli. We
      conclude by discussing progress toward integrated theories for hypocretin
      modulation of divergent behavioral domains. 

PMID- 25050888
TI  - FTY720 induces apoptosis of M2 subtype acute myeloid leukemia cells by targeting
      sphingolipid metabolism and increasing endogenous ceramide levels.
AB  - The M2 subtype Acute Myeloid Leukemia (AML-M2) with t(8;21) represents an unmet
      challenge because of poor clinical outcomes in a sizable portion of patients. In
      this study,we report that FTY720 (Fingolimod), a sphingosine analogue and an FDA
      approved drug for treating of multiple sclerosis, shows antitumorigenic activity
      against the Kasumi-1 cell line, xenograft mouse models and leukemic blasts
      isolated from AML-M2 patients with t(8;21) translocation. Primary investigation
      indicated that FTY720 caused cell apoptosis through caspases and protein
      phosphatase 2A (PP2A) activation. Transcriptomic profiling further revealed that
      FTY720 treatment could upregulate AML1 target genes and interfere with genes
      involved in ceramide synthesis. Treatment with FTY720 led to the elimination of
      AML1-ETO oncoprotein and caused cell cycle arrest. More importantly, FTY720
      treatment resulted in rapid and significant increase of pro-apoptotic ceramide
      levels, determined by high-performance liquid chromatography-electrospray
      ionization tandem mass spectrometry based lipidomic approaches. Structural
      simulation model had also indicated that the direct binding of ceramide to
      inhibitor 2 of PP2A (I2PP2A) could reactivate PP2A and cause cell death. This
      study demonstrates, for the first time, that accumulation of ceramide plays a
      central role in FTY720 induced cell death of AML-M2 with t(8;21). Targeting
      sphingolipid metabolism by using FTY720 may provide novel insight for the drug
      development of treatment for AML-M2 leukemia. 

PMID- 25050890
TI  - Researchers should use more data, not just the HIV sequence compendium, for
      epidemiology and other HIV research.

PMID- 25050889
TI  - IGF-IR signal transduction protein content and its activation by IGF-I in human
      placentas: relationship with gestational age and birth weight.
AB  - INTRODUCTION: The human placenta expresses the IGF-I and IGF-IR proteins and
      their intracellular signal components (IRS-1, AKT and mTOR). The aim of this
      study was to assess the IGF-IR content and activation of downstream signaling
      molecules in placentas from newborns who were classified by gestational age and
      birth weight. We studied placentas from 25 term appropriate (T-AGA), 26 term
      small (T-SGA), 22 preterm AGA (PT-AGA), and 20 preterm SGA (PT-SGA) newborns. The
      total and phosphorylated IGF-IR, IRS-1, AKT, and mTOR contents were determined by
      Western Blot and normalized by actin or with their respective total content. The
      effect of IGF-I was determined by stimulating placental explants with recombinant
      IGF-I 10-8 mol/L for 15, 30, and 60 minutes. RESULTS: The IGF-IR content was
      higher in T-SGA compared to T-AGA placentas, and the IRS-1 content was higher in
      PT-placentas compared with their respective T-placentas. The effect of IGF-I on
      the phosphorylated forms of IGF-IR was increased in T-SGA (150%) and PT-SGA
      (300%) compared with their respective AGA placentas. In addition, AKT serine
      phosphorylation was higher in PT-SGA compared to PT-AGA and T-SGA placentas (90%
      and 390% respectively). CONCLUSION: The higher protein content and response to
      IGF-I of IGF-IR, IRS-1, and AKT observed in SGA placentas may represent a
      compensatory mechanism in response to fetal growth restriction.

PMID- 25050891
TI  - In silico prediction of the T-cell and IgE-binding epitopes of Per a 6 and Bla g
      6 allergens in cockroaches.
AB  - Per a 6 and Bla g 6 are cockroach allergens found in Periplaneta americana and
      Blattella germanica, respectively. The objective of the present study was to
      predict the B- and T-cell epitopes of the Per a 6 and Bla g 6 allergens. Three
      immunoinformatics tools, the DNAStar Protean system, the Bioinformatics Predicted
      Antigenic Peptides system and the BepiPred 1.0 server, were used to predict the
      potential B-cell epitopes, while Net-MHCIIpan-2.0 and NetMHCII-2.2 were used to
      predict the T-cell epitopes of the two allergens. As a result, seven peptides
      were predicted in the Per a 6 allergen and seven peptides were predicted in the
      Bla g 6 allergen in the B-cell epitope predictions. In the T-cell prediction, the
      Per a 6 allergen was predicted to have nine strongly binding nonamer core epitope
      sequences (IC50<50 nm) and 28 weakly binding sequences (50 nm<IC50<500 nm), while
      the Bla g 6 allergen was predicted to have nine strong binders and 25 weak
      binders. These results may be useful for peptide-based vaccine designs.

PMID- 25050893
TI  - An investigation of moral distress experienced by occupational therapists.
AB  - This study used a quantitative survey design to investigate the existence of
      moral distress among occupational therapists. The Moral Distress Scale-Revised
      (MDS-R-OHPA) was distributed to a random sample of 600 members of the American
      Occupational Therapy Association (AOTA). The results of this explorative study
      found that occupational therapists reported moderate levels of moral distress
      with occupational therapists working in geriatric settings reporting higher
      levels of moral distress than occupational therapists who work in physical
      disability settings, although the difference was not statistically significant.
      However, occupational therapists who were considering leaving their current
      position reported the highest levels of moral distress. These initial findings
      are discussed as well as the need for further research.

PMID- 25050896
TI  - Palladium-decorated hydrogen-gas sensors using periodically aligned graphene
      nanoribbons.
AB  - Polymer residue-free graphene nanoribbons (GNRs) of 200 nm width at 1 MUm pitch
      were periodically generated in an area of 1 cm(2) via laser interference
      lithography using a chromium interlayer prior to photoresist coating. High
      quality GNRs were evidenced by atomic force microscopy, micro-Raman spectroscopy,
      and X-ray photoelectron spectroscopy measurements. Palladium nanoparticles were
      then deposited on the GNRs as catalysts for sensing hydrogen gases, and the GNR
      array was utilized as an electrically conductive path with less electrical noise.
      The palladium-decorated GNR array exhibited a rectangular sensing curve with
      unprecedented rapid response and recovery properties: 90% response within 60 s at
      1000 ppm and 80% recovery within 90 s in nitrogen ambient. In addition, reliable
      and repeatable sensing behaviors were revealed when the array was exposed to
      various gas concentrations even at 30 ppm. 

PMID- 25050894
TI  - Reducing deaths from severe pneumonia in children in Malawi by improving delivery
      of pneumonia case management.
AB  - OBJECTIVE: To evaluate the pneumonia specific case fatality rate over time
      following the implementation of a Child Lung Health Programme (CLHP) within the
      existing government health services in Malawi to improve delivery of pneumonia
      case management. METHODS: A prospective, nationwide public health intervention
      was studied to evaluate the impact on pneumonia specific case fatality rate (CFR)
      in infants and young children (0 to 59 months of age) following the
      implementation of the CLHP. The implementation was step-wise from October 1st
      2000 until 31st December 2005 within paediatric inpatient wards in 24 of 25
      district hospitals in Malawi. Data analysis compared recorded outcomes in the
      first three months of the intervention (the control period) to the period after
      that, looking at trend over time and variation by calendar month, age group,
      severity of disease and region of the country. The analysis was repeated
      standardizing the follow-up period by using only the first 15 months after
      implementation at each district hospital. FINDINGS: Following implementation,
      47,228 children were admitted to hospital for severe/very severe pneumonia with
      an overall CFR of 9.8%. In both analyses, the highest CFR was in the children 2
      to 11 months, and those with very severe pneumonia. The majority (64%) of cases,
      2-59 months, had severe pneumonia. In this group there was a significant effect
      of the intervention Odds Ratio (OR) 0.70 (95%CI: 0.50-0.98); p = 0.036), while in
      the same age group children treated for very severe pneumonia there was no
      interventional benefit (OR 0.97 (95%CI: 0.72-1.30); p = 0.8). No benefit was
      observed for neonates (OR 0.83 (95%CI: 0.56-1.22); p = 0.335). CONCLUSIONS: The
      nationwide implementation of the CLHP significantly reduced CFR in Malawian
      infants and children (2-59 months) treated for severe pneumonia. Reasons for the
      lack of benefit for neonates, infants and children with very severe pneumonia
      requires further research.

PMID- 25050897
TI  - A functional role of the sky's polarization pattern for orientation in the
      greater mouse-eared bat.
AB  - Animals can call on a multitude of sensory information to orient and navigate.
      One such cue is the pattern of polarized light in the sky, which for example can
      be used by birds as a geographical reference to calibrate other cues in the
      compass mechanism. Here we demonstrate that the female greater mouse-eared bat
      (Myotis myotis) uses polarization cues at sunset to calibrate a magnetic compass,
      which is subsequently used for orientation during a homing experiment. This
      renders bats the only mammal known so far to make use of the polarization pattern
      in the sky. Although there is currently no clear understanding of how this cue is
      perceived in this taxon, our observation has general implications for the sensory
      biology of mammalian vision. 

PMID- 25050898
TI  - Resistance training does not protect against increases in plasma cytokine levels
      among germ cell cancer patients during and after chemotherapy.
AB  - CONTEXT: Testicular germ cell cancer (GCC) patients treated with cisplatin
      etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an
      increased risk of late-occurring morbidities, which may be associated with
      changes in the inflammatory profile. OBJECTIVE: The objective of the study was to
      explore plasma cytokine concentrations in GCC patients randomized to resistance
      training or usual care during BEP, in comparison with healthy controls.
      DESIGN/SETTING: This was a randomized controlled trial in GCC patients enrolled
      from an oncology clinic, including a healthy reference group for comparison
      purposes. OUTCOME MEASURES: Plasma granulocyte macrophage colony-stimulating
      factor, interferon-gamma, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-alpha
      were measured in fasting blood samples from GCC patients randomized to resistance
      training (INT; n = 15) or usual care (CON; n = 15) and healthy age-matched
      controls (REF; n = 19). Clinical toxicity assessments and patient-reported end
      points were also recorded. RESULTS: CON and INT were balanced at baseline.
      Compared with REF, CON had higher concentrations of IL-10, IL-6, and interferon
      gamma, and INT had higher concentrations of IL-6, IL-8 and TNF-alpha (all P <
      .05). At the end of therapy, concentrations of IL-6, IL-8, and IL-10 increased in
      both GCC groups (all P < .01). Three months after therapy, all cytokine
      concentrations were comparable with the pretreatment levels in both GCC-groups
      but remained elevated compared with REF (P < .05). Changes in TNF-alpha
      correlated with pulmonary toxicity (P < .01). At the end of therapy, IL-6
      concentrations correlated with quality of life (P < .05) and fatigue (P < .01).
      CONCLUSION: GCC patients treated with BEP display consistently elevated levels of
      systemic inflammatory markers compared with healthy controls. Resistance training
      during therapy has no impact on plasma cytokine concentrations.

PMID- 25050899
TI  - Serum Sema3A is in a weak positive association with bone formation marker
      osteocalcin but not related to bone mineral densities in postmenopausal women.
AB  - CONTEXT: The chemorepellent semaphorin-3A (Sema3A) was shown to favor bone
      metabolism in mice, but its bone effects in humans are not described. OBJECTIVE:
      The aim of the study was to investigate the associations between serum Sema3A,
      bone biochemical markers, and bone mineral densities (BMDs) in women. DESIGN,
      SETTING, AND PARTICIPANTS: This was a cross-sectional study involving 1012 pre-
      and postmenopausal women. MAIN OUTCOME MEASURES: Fasting serum Sema3A,
      osteocalcin (Ocn), and cross-linked C-telopeptide of type 1 collagen were
      measured. Dual-energy X-ray absorptiometry was performed to determine the BMDs at
      the lumbar spine and femoral neck. History of osteoporotic fractures was reported
      by the participants. RESULTS: In postmenopausal women (n = 860), a significant
      positive association between Sema3A and Ocn levels was demonstrated (r = 0.077, P
      = 0.025) when age was adjusted. The serum Ocn level was significantly higher in
      the fourth quartile of serum Sema3A as compared with the first quartile (21.09 +/
      0.56 ng/mL vs 19.45 +/- 0.44 ng/mL, P = .018). Serum Sema3A concentrations were
      similar in subjects with normal BMD, osteopenia or osteoporosis, and those with
      and without osteoporotic fractures. Multivariate stepwise regression analysis
      revealed that cross-linked C-telopeptide of type 1 collagen, body mass index,
      creatinine, Sema3A, L1-4 BMDs, and age were determinants of Ocn (adjusted R(2)
      for the model = 0.532, P < .001) . CONCLUSIONS: The positive correlation between
      Sema3A and bone formation marker Ocn revealed in this human study partly supports
      the recently findings in mice studies. However, the general effects of Sema3A on
      bone metabolism are weak and not clear as evidenced by lack of association
      between this parameter and BMDs and osteoporotic fractures.

PMID- 25050900
TI  - Exome sequencing identifies a novel homozygous mutation in the phosphate
      transporter SLC34A1 in hypophosphatemia and nephrocalcinosis.
AB  - CONTEXT: Two Argentinean siblings (a boy and a girl) from a nonconsanguineous
      family presented with hypercalcemia, hypercalciuria, hypophosphatemia, low
      parathyroid hormone (PTH), and nephrocalcinosis. OBJECTIVE: The goal of this
      study was to identify genetic causes of the clinical findings in the two
      siblings. DESIGN: Whole exome sequencing was performed to identify disease
      causing mutations in the youngest sibling, and a candidate variant was screened
      in other family members by Sanger sequencing. In vitro experiments were conducted
      to determine the effects of the mutation that was identified. PATIENTS AND OTHER
      PARTICIPANTS: Affected siblings (2 y.o. female and 10 y.o male) and their parents
      were included in the study. Informed consent was obtained for genetic studies.
      RESULTS: A novel homozygous mutation in the gene encoding the renal sodium
      dependent phosphate transporter SLC34A1 was identified in both siblings
      (c.1484G>A, p.Arg495His). In vitro studies showed that the p.Arg495His mutation
      resulted in decreased phosphate uptake when compared to wild-type SLC34A1.
      CONCLUSIONS: The homozygous G>A transition that results in the substitution of
      histidine for arginine at position 495 of the renal sodium-dependent phosphate
      transporter, SLC34A1, is involved in disease pathogenesis in these patients. Our
      report of the second family with two mutated SLC34A1 alleles expands the known
      phenotype of this rare condition.

PMID- 25050901
TI  - Circulating betatrophin concentrations are decreased in human obesity and type 2
      diabetes.
AB  - CONTEXT: Betatrophin is a secreted protein recently involved in beta-cell
      replication with a potential role in type 2 diabetes mellitus (T2D). OBJECTIVE:
      The aim of the present study was to compare the circulating concentrations of
      betatrophin in human obesity and T2D. DESIGN, SETTING, AND PARTICIPANTS: Serum
      concentrations of betatrophin were measured by ELISA in 153 subjects: 75 obese
      normoglycemic subjects (OB-NG), 30 obese subjects with impaired glucose tolerance
      (OB-IGT), and 15 obese subjects with T2D (OB-T2D) matched by sex, age, and body
      adiposity, in comparison with 33 lean normoglycemic individuals (LN-NG). RESULTS:
      Circulating levels of betatrophin were significantly decreased in obese
      individuals and further diminished in IGT and T2D participants (LN-NG, 45.1 +/-
      24.4 ng/mL; OB-NG, 26.9 +/- 15.4 ng/mL; OB-IGT, 18.3 +/- 10.7 ng/mL; OB-T2D, 13.5
      +/- 8.8 ng/mL; P < .001). A marked sexual dimorphism was found, with betatrophin
      levels being significantly higher in women than in men (males, 21.1 +/- 16.0
      ng/mL; females, 34.1 +/- 20.1 ng/mL; P < .001). Interestingly, betatrophin levels
      were positively correlated with the quantitative insulin sensitivity check index
      (r = 0.46; P < .001) and with high-density lipoprotein-cholesterol concentrations
      (r = 0.51; P < .001). CONCLUSIONS: We conclude that serum betatrophin is
      decreased in human obesity, being further reduced in obesity-associated insulin
      resistance. Betatrophin levels are closely related to obesity-associated
      cardiometabolic risk factors, emerging as a potential biomarker of insulin
      resistance and T2D.

PMID- 25050902
TI  - Endogenous incretin hormone augmentation of acute insulin secretion in
      normoglycemic relatives of type 2 diabetic subjects: a 10-year retrospective
      pathophysiological study.
AB  - AIMS/HYPOTHESIS: The pathophysiological role of gut incretin hormone
      argumentation on acute insulin release in the genesis of type 2 diabetes (TDM2)
      is uncertain. We examined retrospectively at 0 year and 10 years the endogenous
      incretin hormone action (IHA) on acute insulin release and glucose tolerance in
      normoglycemic relatives (REL) of TDM2 and control (CON) subjects. METHODS: At 0
      year and 10 years, glucose tolerance, paired oral glucose tolerance test (OGTT)-
      and i.v. glucose tolerance test (IVGTT)-induced acute (0-30 min) insulin release
      (insulinogenic index IGIOGTT and IGIIVGTT), and IHA were calculated in 19 REL and
      18 CON subjects by cross-correlation linear regression slope analyses of the OGTT
      (0-30 min) matched insulin/glucose profiles vs the early (0-5 min) and delayed
      (10-30 min) IVGTT profiles. RESULTS: At 0 year, REL and CON IGIOGTT and IGIIVGTT
      were similar, but the REL 2- to 5-min IVGTT-induced insulin responses were
      reduced (P < .03). By 10 years, glucose tolerance deteriorated in nine
      dysglycemic REL (RELDGT), with raised fasting glucose and 2-hour OGTT glucose.
      Retrospective analyses of RELDGT at 0 year demonstrated raised proinsulin/insulin
      molar ratios and fasting glucose and a reduced IVGTT insulin/glucose slope, but
      the RELDGT IHA was similar to normoglycemic REL (RELNGT) and CON. By 10 years,
      RELDGT OGTT insulin/glucose slopes were reduced (P = .03-.01), but more so for
      the early (P < .01-.003) and delayed (P < .005-.002) IVGTT slopes, compared to
      the normoglycaemic REL and CON subjects. CONCLUSIONS: IHA on acute insulin
      release is maintained in normoglycemic REL and CON subjects over 10 years. The
      apparent deterioration in IHA in RELDGT is consistent with a progressive failure
      of acute beta-cell function over 10 years.

PMID- 25050903
TI  - Long-term efficacy of ultrasound-guided laser ablation for benign solid thyroid
      nodules. Results of a three-year multicenter prospective randomized trial.
AB  - BACKGROUND: The aim of the present trial on ultrasound (US)-guided laser ablation
      therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy,
      side effects, and predictability of outcomes in different centers operating with
      the same procedure. PATIENTS: Two hundred consecutive patients were randomly
      assigned to a single LAT session (group 1, 101 cases) or to follow-up (group 2,
      99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid
      nodule with volume of 6-17 mL, repeat benign cytological findings, normal thyroid
      function, no autoimmunity, and no thyroid gland treatment. METHODS: Group 1: LAT
      was performed in a single session with two optical fibers, a 1064 nm Nd-YAG laser
      source, and an output power of 3 W. Volume and local symptom changes were
      evaluated 1, 6, 12, 24, and 36 months after LAT. Side effects and tolerability of
      treatment were registered. Group 2: Follow-up with no treatment. RESULTS: One
      patient was lost to follow-up in each group. Group 1: Volume decrease after LAT
      was -49 +/- 22%, -59 +/- 22%, -60 +/- 24%, and -57 +/- 25% at 6, 12, 24, and 36
      months, respectively (P < .001 vs baseline). LAT resulted in a nodule reduction
      of >50% in 67.3% of cases (P < .001). Local symptoms decreased from 38 to 8% of
      cases (P = .002) and cosmetic signs from 72 to 16% of cases (P = .001). Baseline
      size, presence of goiter (P = .55), or US findings (fluid component <= 20% [P =
      .84], halo [P = .46], vascularization [P = .98], and calcifications [P = .06])
      were not predictive factors of a volume decrease > 50%. The procedure was well
      tolerated in most (92%) cases. No changes in thyroid function or autoimmunity
      were observed. In group 2, nodule volume increased at 36 months (25 +/- 42%; P =
      .04). The efficacy and tolerability of the procedure were similar in different
      centers. CONCLUSIONS: A single LAT treatment of solid nodules results in
      significant and persistent volume reduction and local symptom improvement, in the
      absence of thyroid function changes.

PMID- 25050904
TI  - Growth hormone signaling in muscle and adipose tissue of obese human subjects:
      associations with measures of body composition and interaction with resveratrol
      treatment.
AB  - CONTEXT: Growth hormone (GH) secretion is reduced in obesity, despite normal
      serum insulin-like growth factor I (IGF-1) levels, but the association between
      obesity and the GH signaling is unknown. Furthermore, SIRT1, an nicotinamide
      adenine dinucleotide-dependent protein deacetylase, reduces hepatic IGF-1
      production in mice via blunting of GH-induced STAT5 signaling. OBJECTIVE: To
      study GH signaling in muscle and fat in obese subjects and the interaction with
      concomitant administration of the putative SIRT1 activator resveratrol, and to
      assess the effects of inhibiting or knocking down SIRT1 on GH regulated genes in
      vitro. DESIGN AND PARTICIPANTS: Twenty-four obese males were examined in a
      randomized, double blinded, parallel-group study with resveratrol or placebo
      treatment for 5 weeks followed by a GH bolus. Muscle and fat biopsies were
      collected before and after GH. Body composition was assessed by DEXA and MRI.
      MAIN OUTCOME MEASURE: (1) Effect of body composition and age on GH-stimulated
      STAT5b phosphorylation and IGF-1, SOCS2, and CISH mRNA in muscle and fat. (2) The
      impact of resveratrol treatment on GH activity. (3) Impact of inhibiting or
      knocking down SIRT1 on effects of GH in vitro. RESULTS: Significant GH-induced
      STAT5b phosphorylation in muscle and fat in obese subjects was recorded together
      with increased CISH and SOCS2 mRNA. GH-induced STAT5b phosphorylation in muscle
      correlated positively with age [r = 0.53, p < 0.01], but not with body
      composition. Resveratrol administration had no impact on body composition, serum
      IGF-1, or GH signaling in vivo, and SIRT1 knock down or inhibition did not affect
      GH signaling in vitro. CONCLUSION: (1) GH induced STAT5b phosphorylation is
      detectable in muscle and fat in adult males with simple obesity, but is not
      determined by body composition. (2) Resveratrol supplementation does not impact
      circulating IGF-1 levels or GH signaling in human muscle and fat. (3) Our data
      speak against a major impact of SIRT1on GH action in human subjects.

PMID- 25050905
TI  - Urinary phthalate metabolites and the risk of low bone mineral density and
      osteoporosis in older women.
AB  - CONTEXT: Experimental studies have demonstrated that phthalate exposure is
      associated with skeletal malformations and an imbalance in bone homeostasis.
      However, few studies have evaluated the association between phthalates and human
      bone health. OBJECTIVES: We evaluated whether urinary phthalate metabolites were
      associated with total hip and femur neck bone mineral density (BMD) and
      osteoporosis in postmenopausal women (>=50 y old). DESIGN: We analyzed data from
      the 2005-2008 National Health and Nutrition Examination Survey (NHANES) for 398
      postmenopausal women >= 50 years of age. Eleven phthalate metabolites were
      selected with a detection rate >= 60% and were categorized into quartiles. Total
      hip and femur neck BMD measurements were obtained using dual-energy x-ray
      absorptiometry bone densitometry. Osteoporosis was defined based on the World
      Health Organization criteria, with thresholds of 0.64 and 0.56 g/cm(2) or less
      for the total hip and femur neck, respectively. RESULTS: Increases in the urinary
      mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, and monobenzyl
      phthalate quartiles were significantly associated with reduced total hip or femur
      neck BMD. Postmenopausal women with the highest levels of mono-(3-carboxypropyl)
      phthalate, mono(carboxyoctyl) phthalate, and the sum of the three di(2
      ethylhexyl) phthalate metabolites were more likely to have an increased risk for
      total hip or femur neck osteoporosis than those with the lowest levels of these
      metabolites. CONCLUSION: Urinary phthalate metabolites were associated with low
      BMD and high osteoporosis risk in postmenopausal women. Our findings suggest that
      background phthalate exposure may unfavorably affect bone homeostasis and BMD in
      humans.

PMID- 25050906
TI  - Inhibition by caffeic acid of the influenza A virus multiplication in vitro.
AB  - Caffeic acid has been shown to inhibit the multiplication of influenza A virus in
      vitro, whereas caffeine, quinic acid and chlorogenic acid do not. Caffeic acid
      has also been shown to have antiviral activity against herpes simplex virus (DNA
      virus) and polio virus (RNA virus). In the present study, a comparison of the one
      step growth curve of the influenza virus in the presence of caffeic acid with
      that in the absence of the reagent showed that an eclipse period of the virus
      multiplication in the infected cells was not affected by the reagent, while the
      progeny virus yield was markedly decreased in the presence of caffeic acid. In
      additional experiments, it was found that the addition of caffeic acid at an
      early time point post-infection (within 3 h post-infection) was mandatory for
      extensive antiviral activity, suggesting that a major target of the reagent
      exists in the early stages of infection. Simultaneously with the decrease in the
      progeny virus yield, both the virus-induced cytopathic effects and apoptotic
      nuclear fragmentation were markedly suppressed by the reagent, suggesting that
      caffeic acid suppresses, at least temporally, the degeneration of the virus
      infected cells and that the observed antiviral activity is likely not the
      secondary result of the cytotoxic effects of the reagent. These results suggest
      the potential pharmacological use of caffeic acid or its derivatives as an
      antiviral drug against influenza A virus.

PMID- 25050908
TI  - A 20-year prospective study of Wilms tumor and other kidney tumors: a report from
      Hong Kong pediatric hematology and oncology study group.
AB  - BACKGROUND: Renal tumors are one of the most common tumors in children. We aim at
      evaluating the characteristics and the outcome of Wilms tumor and other malignant
      kidney tumors in Hong Kong. PROCEDURE: Between January 1990 to December 2010, 68
      patients under the age of 18 with malignant renal tumors were diagnosed and
      received treatment in Hong Kong. Clinical records were updated regularly.
      Prognostic factors and survival rate were evaluated. RESULTS: Fifty-four patients
      were diagnosed with Wilms tumor. The annual incidence was estimated to be 2.29
      per million. The mean age was 38 months. Median follow-up was 9.2 years. The
      event-free survival and overall survival rate at 10 years were 85.2% and 92.6%,
      respectively. A pair of siblings with familial extrarenal Wilms tumor was
      included. Pulmonary metastasis did exhibit a significant difference in survival
      rate. Eight cases of clear cell sarcoma of the kidneys were reported and the
      survival rate was 100%. CONCLUSIONS: The clinical characteristics and outcome of
      the patients diagnosed Wilms tumor were comparable with other developed
      countries. Relatively high proportion and excellent outcome were found in clear
      cell sarcoma of the kidneys.

PMID- 25050907
TI  - Transitive and anti-transitive emergent relations in pigeons: support for a
      theory of stimulus-class formation.
AB  - Stimulus class formation is inferred when conditional discrimination training
      yields new (emergent) conditional relations between the training stimuli. The
      present experiments demonstrated two such relations in pigeons after successive
      matching-to-sample training. Experiment 1 showed that transitivity (AC matching)
      emerged after training on AB and BC arbitrary matching plus BB identity matching:
      pigeons responded relatively more to the comparisons on AC test trials in which
      both the A samples and C comparisons were elements of reinforced arbitrary
      baseline relations involving the same nominal B stimulus. Experiment 2 showed the
      opposite effect ("anti-transitivity") after training on the same arbitrary
      relations but with BB oddity instead: pigeons responded relatively more to the
      comparisons on AC test trials in which the A sample was an element of a
      reinforced baseline relation and the C comparison was an element of a non
      reinforced baseline relation, or vice versa. Experiment 2 also showed that AB and
      BC training alone generally does not yield an emergent effect. These findings
      extend the range of emergent phenomena observed in non-human animals and are
      consistent with predictions from Urcuioli's (2008) theory of pigeons' stimulus
      class formation. This article is part of a Special Issue entitled: Tribute to Tom
      Zentall. 

PMID- 25050909
TI  - Identification of a positively charged platform in Staphylococcus aureus HtsA
      that is essential for ferric staphyloferrin A transport.
AB  - In response to iron starvation, Staphylococcus aureus secretes both
      staphyloferrin A and staphyloferrin B, which are high-affinity iron-chelating
      molecules. The structures of both HtsA and SirA, the ferric-staphyloferrin A
      [Fe(III)-SA] and ferric-staphyloferrin B [Fe(III)-SB] receptors, respectively,
      have recently been determined. The structure of HtsA identifies a novel form of
      ligand entrapment composed of many positively charged residues. Through ionic
      interactions, the binding pocket appears highly adapted for the binding of the
      highly anionic siderophore SA. However, biological validation of the importance
      of the nine SA-interacting residues (six arginines, one tyrosine, one histidine,
      and one lysine) has not been previously performed. Here, we mutated each of the
      Fe(III)-SA-interacting residues in HtsA and found that substitutions R104A,
      R126A, H209A, R306A, and R306K resulted in a reduction of binding affinity of
      HtsA for Fe(III)-SA. While mutation of almost all proposed ligand-interacting
      residues decreased the ability of S. aureus cells to transport (55)Fe(III)-SA, S.
      aureus expressing HtsA R104A, R126A, R306A, and R306K showed the greatest
      transport defects and were incapable of growth in iron-restricted growth media in
      a SA-dependent manner. These three residues cluster together and, relative to
      other residues in the binding pocket, move very little between the apo and closed
      holo structures. Their essentiality for receptor function, together with
      structural information, suggests that they form a positively charged platform
      that is required for initial contact with the terminal carboxyl groups of the two
      citrates in the Fe(III)-SA complex. This is a likely mechanism by which HtsA
      discerns iron-bound SA from iron-free SA. 

PMID- 25050910
TI  - Bonding interactions between sulfur dioxide (SO2) and mono-ruthenium(II)
      substituted Keggin-type polyoxometalates: electronic structures of ruthenium-SO2
      adducts.
AB  - Density functional theory (DFT) calculations and natural bond orbital (NBO)
      analysis were carried out to investigate the electronic structures and bonding
      features between the ruthenium(ii) atom and the SO2 molecule in two ruthenium
      sulfur dioxide (SO2) adducts, trans-Ru(NH3)4(SO2)Cl(+) and
      [{SiW11O39}Ru(II)(SO2)](6-). In addition, the bonding interactions between SO2
      and the metal-ruthenium fragment were determined by binding energy (DeltaEabs)
      calculation and electronic structures. The results indicate that the eta(1)-S
      planar model in both trans-Ru(NH3)4(SO2)Cl(+) and [{SiW11O39}Ru(II)(SO2)](6-) are
      more favorable. NBO analysis of the bonding interaction between ruthenium and
      sulfur centers in the [{SiW11O39}Ru(II)(SO2)](6-) complex shows that it possesses
      a sigma and a pi bond. It predicts that the polyoxometalate [SiW11O39Ru](6-) can
      serve as a potential adsorbent for the SO2 molecule because of the strong Ru-S
      bond relative to Ru(NH3)4Cl(+). 

PMID- 25050911
TI  - UV photochemistry of peroxyformic acid (HC(O)OOH): an experimental and
      computational study investigating 355 nm photolysis.
AB  - The photochemistry of peroxyformic acid (PFA), a molecule of atmospheric interest
      exhibiting internal hydrogen bonding, is examined by exciting the molecule at 355
      nm and detecting the nascent OH fragments using laser-induced fluorescence. The
      OH radicals are found to be formed in their ground electronic state with the vast
      majority of available energy appearing in fragment translation. The OH fragments
      are vibrationally cold (v" = 0) with only modest rotational excitation. The
      average rotational energy is determined to be 0.35 kcal/mol. Further, the degree
      of OH rotational excitation from PFA is found to be significantly less than that
      arising from the dissociation of H2O2 as well as other hydroperoxides over the
      same wavelength. Ab initio calculation at the EOM-CCSD level is used to
      investigate the first few electronic excited states of PFA. Differences in the
      computed torsional potential between PFA and H2O2 help rationalize the observed
      variation in their respective OH fragment rotational excitation. The calculations
      also establish that the electronic excited state of PFA accessed in the near UV
      is of (1)A" symmetry and involves a sigma*(O-O) <- n(O) excitation. Additionally,
      the UV absorption cross section of PFA at 355 and 282 nm is estimated by
      comparing the yield of OH from PFA at these wavelengths to that from hydrogen
      peroxide for which the absorption cross sections is known.

PMID- 25050912
TI  - Cyclometalated N-heterocyclic carbene complexes of ruthenium for access to
      electron-rich silylene complexes that bind the Lewis acids CuOTf and AgOTf.
AB  - The synthesis of the cyclometalated complexes Cp*Ru(IXy-H) (2) [IXy = 1,3-bis(2,6
      dimethylphenyl)imidazol-2-ylidene; IXy-H = 1-(2-CH2C6H3-6-methyl)-3-(2,6
      dimethylphenyl)imidazol-2-ylidene-1-yl (the deprotonated form of IXy); Cp* =
      eta(5)-C5Me5] and Cp*Ru(IXy-H)(N2) (3) was achieved by dehydrochlorination of
      Cp*Ru(IXy)Cl (1) with KCH2Ph. Complexes 2 and 3 activate primary silanes (RSiH3)
      to afford the silyl complexes Cp*(IXy-H)(H)RuSiH2R [R = p-Tol (4), Mes (5), Trip
      (6)]. Density functional theory studies indicated that these complexes are close
      in energy to the corresponding isomeric silylene species Cp*(IXy)(H)Ru?SiHR.
      Indeed, reactivity studies indicated that various reagents trap the silylene
      isomer of 6, Cp*(IXy)(H)Ru?SiHTrip (6a). Thus, benzaldehyde reacts with 6 to give
      the [2 + 2] cycloaddition product 7, while 4-bromoacetophenone reacts via C-H
      bond cleavage and formation of the enolate Cp*(IXy)(H)2RuSiH[OC(?CH2)C6H4Br]Trip
      (8). Addition of the O-H bond of 2,6-dimethylphenol across the Ru?Si bond of 6a
      gives Cp*(IXy)(H)2RuSiH(2,6-Me2C6H3O)Trip (9). Interestingly, CuOTf and AgOTf
      also react with 6 to provide unusual Lewis acid-stabilized silylene complexes in
      which MOTf bridges the Ru-Si bond. The AgOTf complex, which was
      crystallographically characterized, exhibits a structure similar to that of
      [Cp*((i)Pr3P)Ru(MU-H)2SiHMes](+), with a three-center, two-electron Ru-Ag-Si
      interaction. Natural bond orbital analysis of the MOTf complexes supported this
      type of bonding and characterized the donor interaction with Ag (or Cu) as
      involving a delocalized interaction with contributions from the carbene,
      silylene, and hydride ligands of Ru. 

PMID- 25050913
TI  - Carbon and terahertz nanotechnology: a promising alliance.

PMID- 25050914
TI  - New insights into the consequences of post-windthrow salvage logging revealed by
      functional structure of saproxylic beetles assemblages.
AB  - Windstorms, bark beetle outbreaks and fires are important natural disturbances in
      coniferous forests worldwide. Wind-thrown trees promote biodiversity and
      restoration within production forests, but also cause large economic losses due
      to bark beetle infestation and accelerated fungal decomposition. Such damaged
      trees are often removed by salvage logging, which leads to decreased biodiversity
      and thus increasingly evokes discussions between economists and ecologists about
      appropriate strategies. To reveal the reasons behind species loss after salvage
      logging, we used a functional approach based on four habitat-related ecological
      traits and focused on saproxylic beetles. We predicted that salvage logging would
      decrease functional diversity (measured as effect sizes of mean pairwise
      distances using null models) as well as mean values of beetle body size, wood
      diameter niche and canopy cover niche, but would increase decay stage niche. As
      expected, salvage logging caused a decrease in species richness, but led to an
      increase in functional diversity by altering the species composition from habitat
      filtered assemblages toward random assemblages. Even though salvage logging
      removes tree trunks, the most negative effects were found for small and
      heliophilous species and for species specialized on wood of small diameter. Our
      results suggested that salvage logging disrupts the natural assembly process on
      windthrown trees and that negative ecological impacts are caused more by
      microclimate alteration of the dead-wood objects than by loss of resource amount.
      These insights underline the power of functional approaches to detect ecosystem
      responses to anthropogenic disturbance and form a basis for management decisions
      in conservation. To mitigate negative effects on saproxylic beetle diversity
      after windthrows, we recommend preserving single windthrown trees or at least
      their tops with exposed branches during salvage logging. Such an extension of the
      green-tree retention approach to windthrown trees will preserve natural
      succession and associated communities of disturbed spruce forests. 

PMID- 25050915
TI  - Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS
      and disrupting AKT/mTOR signaling.
AB  - Temozolomide (TMZ), a DNA alkylating agent, represents the most important
      chemotherapeutic option for the treatment of glioblastoma in the clinic. Despite
      its frequent use, the therapeutic efficacy of TMZ remains very limited due to its
      frequent resistance in glioblastoma. Previous evidence suggested that curcumin
      (CUM), an ingredient of the Indian spice turmeric, is able to sensitize
      glioblastoma to TMZ treatment. However, the underlying molecular mechanism
      remains elusive. In the present study, we performed in vitro and in vivo
      experiments to evaluate the interaction of CUM and TMZ on the inhibition of
      glioblastoma and to investigate its potential mechanisms of action using U87MG
      cell lines and xenograft mouse models. We demonstrated that CUM enhanced the
      therapeutic response to TMZ in U87MG glioblastoma by enhancing apoptosis. We then
      proceeded to investigate the potential apoptotic signaling pathways that are
      involved. We observed a synergistic effect of the combination of CUM and TMZ in
      generating reactive oxygen species (ROS) production, suggesting that ROS may
      contribute to the impact of CUM on sensitizing TMZ treatment. We also showed that
      CUM and TMZ treatment alone significantly suppressed phosphorylated AKT and mTOR,
      whereas their combination achieved a more pronounced inhibitory effect. These
      data indicated that blockage of AKT/mTOR signaling appeared to contribute to the
      elevated apoptosis caused by the combination treatment with CUM and TMZ. In
      conclusion, this study provided molecular insights into the effects of CUM on the
      therapeutic response of glioblastoma to TMZ and opened new avenues for optimizing
      the therapeutic effects of TMZ-based therapies. 

PMID- 25050916
TI  - Motility of select ovarian cancer cell lines: effect of extra-cellular matrix
      proteins and the involvement of PAK2.
AB  - The interaction between tumor cells and extracellular matrix (ECM) proteins
      influences cell migration and the invasive behavior of cancer cells. In this
      study, we provide experimental evidence that collagen I and fibronectin affect
      ovarian cancer cell migration. In vitro wound healing assays and transwell
      migration assays were used to measure both total wound healing and directionality
      of individually migrating OV2008 and C13 ovarian cancer cells on glass, collagen
      I and fibronectin. Involvement of p21-activated kinase 2 (Pak2) in the motility
      of these cell lines was investigated using a chemical inhibitor as well as siRNA
      transfection. Culturing ovarian cancer cells on collagen type I (COLL) increased
      the migratory ability of OV2008 and C13 cells by increasing the directional
      migration of cells. In contrast, fibronectin (FN) decreased the migratory ability
      of OV2008 cells by reducing their ability to migrate directionally. When both
      cell lines are cultured on COLL and treated with increasing concentrations of a
      PAK inhibitor (IPA-3), there is a dose-dependent response such that there is a
      decrease in migration with an increase in inhibitor concentration. Further
      experiments utilizing PAK2 knockdown via siRNA transfection demonstrated
      significantly reduced migration of OV2008 cells on COLL as compared to those
      receiving control siRNA. In conclusion, our results indicate that FN and COLL
      affect the motility of the selected ovarian cancer cells lines and the effect of
      COLL is likely mediated, at least in part, by PAK2. A better understanding of the
      molecular events that contribute to tumor invasion and metastasis is crucial for
      developing novel treatment strategies to improve the long-term survival of women
      with ovarian cancer. As PAK2 is involved in motility, it should be further
      explored as a pro-metastatic gene in ovarian cancer. 

PMID- 25050917
TI  - Photo-responsive [2]catenanes: synthesis and properties.
AB  - A series of novel dithienylethene-based macrocycles containing ammonium moieties
      has been synthesized. They have been employed as templates to construct
      [2]catenanes showing their photoisomerization properties by means of a dynamic
      covalent chemistry approach. Their structures have been reliably confirmed by
      NMR, ESI-MS or MALDI-QTOF-MS, and elemental analysis, and their energy-minimized
      structures of open- and closed-ring isomers were investigated by the theoretical
      calculation. Investigation of the photochromic properties of these
      dithienylethene-based [2]catenanes has revealed good reversibility and excellent
      fatigue resistance upon irradiation with UV or visible light. Notably, formation
      of the [2]catenanes enhanced the photochromic properties compared with those of
      the corresponding macrocyclic ammonium salt, implying that the non-covalently
      interacting components of the [2]catenanes could affect the photoswitchable
      properties. 

PMID- 25050918
TI  - Polymethyl methacrylate (PMMA)-bismuth ferrite (BFO) nanocomposite: low loss and
      high dielectric constant materials with perceptible magnetic properties.
AB  - Herein, poly(methyl methacrylate)-bismuth ferrite (PMMA-BFO) nanocomposites were
      successfully prepared by an in situ polymerization method for the first time.
      Initially, the as prepared bismuth ferrite (BFO) nanoparticles were dispersed in
      the monomer, (methyl methacrylate) by sonication. Benzoyl peroxide was used to
      initiate the polymerization reaction in ethyl acetate medium. The nanocomposite
      films were subjected to X-ray diffraction analysis (XRD), (1)H NMR, field
      emission scanning electron microscopy (FESEM), transmission electron microscopy
      (TEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA), infrared
      spectroscopy (IR), dielectric and magnetic characterizations. The dielectric
      measurement of the nanocomposites was investigated at a frequency range of 10 Hz
      to 1 MHz. It was found that the nanocomposites not only showed a significantly
      increased value of the dielectric constant with an increase in the loading
      percentage of BFO as compared to pure PMMA, but also exhibited low dielectric
      loss values over a wide range of frequencies. The values of the dielectric
      constant and dielectric loss of the PMMA-BFO5 (5% BFO loading) sample at 1 kHz
      frequency was found be ~14 and 0.037. The variation of the ferromagnetic response
      of the nanocomposite was consistent with the varying volume percentage of the
      nanoparticles. The remnant magnetization (Mr) and saturation magnetization (Ms)
      values of the composites were found to be enhanced by increasing the loading
      percentage of BFO. The value of Ms for PMMA-BFO5 was found to be ~6 emu g(-1).
      The prima facie observations suggest that the nanocomposite is a potential
      candidate for application in high dielectric constant capacitors. Significantly,
      based on its magnetic properties the composite will also be useful for use in
      hard disk components.

PMID- 25050919
TI  - Identification of regulatory elements directing miR-23a-miR-27a-miR-24-2
      transcriptional regulation in response to muscle hypertrophic stimuli.
AB  - MiRNAs are small non-coding RNAs that significantly regulate the translation of
      protein coding genes in higher organisms. MicroRNAs are involved in almost every
      biological process, including early development, lineage commitment, growth and
      differentiation, cell death, and metabolic control. Misregulation of miRNAs
      belonging to the intergenic miR-23a-miR-27a-miR-24-2 cluster has been recently
      associated to cardiac and skeletal muscle diseases, and they are up-regulated in
      hypertrophic cardiomyopathy and skeletal muscle atrophy. Despite these facts, the
      basal transcriptional regulation of miR-23a/miR-27-a/miR-24-2 cluster and how it
      is altered under pathological conditions remain unclear. In this study, we
      identified and functionally characterized conserved upstream and downstream
      regulatory sequences from the miR-23a-miR-27a-miR-24-2 locus that are implicated
      on its transcriptional control. Our data demonstrate that Srf plays a pivotal
      role in modulating miR-23a-miR-27a-miR-24-2 cluster proximal promoter activity.
      Importantly, pro-hypertrophic signalling pathways such as those driven by
      angiotensin II and norepinephrine also regulate miR-23a-miR-27a-miR-24-2 cluster
      proximal promoter activity. Taking together, our results provide new insights
      into the regulatory networks driving miR-23a-miR-27a-miR-24-2 cluster expression
      in cardiac and skeletal muscles. 

PMID- 25050921
TI  - Parameters affecting the microwave-specific acceleration of a chemical reaction.
AB  - Under appropriate conditions, significant microwave-specific enhancement of the
      reaction rate of an organic chemical reaction can be observed. Specifically, the
      unimolecular Claisen rearrangement of allyl p-nitrophenyl ether (ApNE) dissolved
      in naphthalene was studied under microwave heating and conventional convective
      (thermal) heating. Under constant microwave power, reaching a temperature of 185 
      degrees C, a 4-fold rate enhancement was observed in the microwave over that
      using convective heating; this means that the microwave reaction was proceeding
      at an effective temperature of 202  degrees C. Conversely, under constant
      temperature microwave conditions (200  degrees C), a negligible (~1.5-fold)
      microwave-specific rate enhancement was observed. The largest microwave-specific
      rate enhancement was observed when a series of 300 W pulses, programmed for 145
      175  degrees C and 85-155  degrees C cycles, where 2- and 9-fold rate
      enhancements, over what would be predicted by conventional thermal heating, was
      observed, respectively. The postulated origins of the microwave-specific effect
      are purely thermal and arise from selective heating of ApNE, a microwave
      absorbing reactant in a nonabsorbing solvent. Under these conditions, excess heat
      is accumulated in the domains around the ApNE solute so that it experiences a
      higher effective temperature than the measured temperature of the bulk medium,
      resulting in an accelerated unimolecular rearrangement. 

PMID- 25050920
TI  - FMR1 premutation is an uncommon explanation for premature ovarian failure in Han
      Chinese.
AB  - BACKGROUND: In premature ovarian failure (POF), cessation of menstruation occurs
      before the expected age of menopause. Approximately 1% of women are affected.
      FMR1 premutation was reported to be responsible for up to 3.3%-6.7% of sporadic
      POF and 13% of familial cases in Caucasians, while the data was absent in Chinese
      population. Therefore, the impact of FMR1 CGG repeat on ovarian reserve is needed
      to be investigated in large Chinese cohort. METHODS: The number of FMR1 CGG
      repeat was determined in 379 Han Chinese women with well-defined 46, XX non
      syndromic sporadic POF and 402 controls. The age of menopause onset in respect to
      CGG repeats was further analyzed. RESULTS: The frequency of FMR1 premutation in
      Han Chinese POF was only 0.5% (2/379), although it was higher than that in
      matched controls (0%, 0/402), it was much lower than that reported in Caucasian
      with POF (3.3%-6.7%). The prevalence of intermediate FMR1 (41-54) was not
      increased significantly in sporadic POF than that in controls (2.9% vs. 1.7%, P =
      0.343). However, POF patients more often carried a single additional CGG repeat
      in a single allele than did fertile women (allele-1: 29.7 vs. 28.8, P<0.001;
      allele-2: 32.6 vs. 31.5, P < 0.001). POF patients with both alleles of CGG
      repeats outside (below or above) the normal range (26-34) showed an earlier age
      of cessation of menses than those with two alleles within normal range (hom
      high/high vs. norm: 20.4 +/- 4.8 vs. 24.7 +/- 6.4, p < 0.01; hom-low/high vs.
      norm: 18.7 +/- 1.7 vs. 24.7 +/- 6.4, p < 0.01). CONCLUSIONS: FMR1 premutation
      seems to be an uncommon explanation for POF in Han Chinese. However, having both
      alleles with CGG repeats outside the normal range might still adversely affect
      ovarian aging.

PMID- 25050922
TI  - Microenvironment dependency in Chronic Lymphocytic Leukemia: The basis for new
      targeted therapies.
AB  - Chronic Lymphocytic Leukemia (CLL) is a prototype microenvironment-dependent B
      cell malignancy, in which the neoplastic B cells co-evolve together with a
      supportive tissue microenvironment, which promotes leukemia cell survival,
      growth, and drug-resistance. Chemo-immunotherapy is an established treatment
      modality for CLL patients, resulting in high rates of responses and improved
      survival, especially in low-risk CLL. New, alternative treatments target B-cell
      receptor (BCR) signaling and the Chemokine (C-X-C motif) Receptor 4 (CXCR4)
      Chemokine (C-X-C motif) Ligand 12 (CXCL12) axis, which are key pathways of CLL
      microenvironment cross talk. The remarkable clinical efficacy of inhibitors
      targeting the BCR-associated kinases Bruton's tyrosine kinase (BTK) and
      phosphoinositide 3-kinase delta (PI3Kdelta) challenges established therapeutic
      paradigms and corroborates the central role of BCR signaling in CLL pathogenesis.
      In this review, we discuss the cellular and molecular components of the CLL
      microenvironment. We also describe the emerging therapeutic options for CLL
      patients, with a focus on inhibitors of CXCR4-CXCL12 and BCR signaling. 

PMID- 25050923
TI  - The role of T cells in systemic lupus erythematosus: an update.
AB  - PURPOSE OF REVIEW: To describe our current understanding of the role of T cells
      in the pathophysiology of systemic lupus erythematosus (SLE). RECENT FINDINGS:
      Over the last few years, the dominant role of T cells in autoimmunity and SLE was
      established. Genome-wide-association studies led to the discovery of multiple
      single-nucleotide polymorphisms associated with SLE. Most of these single
      nucleotide polymorphisms fall within the noncoding DNA regions of immune response
      related genes and few seem to contribute to the observed abnormal T cell
      function. The field of epigenetics research developed rapidly and provided us
      with new insights into the observed generalized hypomethylation in SLE T cells,
      the abnormal histone modifications and the role of RNA interference. Old
      observations, such as the decreased interleukin-2 production, are better
      understood with our evolved knowledge of many signal transduction pathways and
      the way they converge and regulate the transcription of different genes in T
      cells. Finally, we are now able to identify subpopulations of T cells, such as
      Th17 and T regulatory cells, and to define their role in SLE. SUMMARY: T cells
      are key players in SLE, and over the last few years our understanding of their
      activation, signal transduction and gene regulation has evolved significantly.

PMID- 25050924
TI  - Pediatric inflammatory brain diseases: a diagnostic approach.
AB  - PURPOSE OF REVIEW: Autoimmune-mediated inflammatory brain diseases represent a
      rapidly evolving area of medicine. The expanding spectrum of disease challenges
      providers as they strive to accurately diagnosis and treat children presenting
      with new onset neuropsychiatric deficits. This review examines recently published
      studies on primary central nervous system vasculitis and autoimmune encephalitis
      and utilizes key distinguishing features to guide a diagnostic approach. RECENT
      FINDINGS: The spectrum of inflammatory brain disease continues to expand with the
      recognition of variable disease phenotypes and targets of the immune system.
      Providers are often overwhelmed by the heterogeneity in clinical features and the
      lack of sensitivity and specificity of diagnostic testing. Recent scientific
      advances have enhanced our ability to diagnose these conditions and provide great
      promise for successful treatment in even severely affected children. SUMMARY: We
      are beginning to recognize the brain's susceptibility to autoimmunity and the
      broad spectrum of phenotypes associated with these conditions. Differentiating
      the various types of inflammatory brain disease remains challenging and benefits
      from a systematic approach.

PMID- 25050925
TI  - Advances in the understanding and treatment of systemic complications in
      Sjogren's syndrome.
AB  - PURPOSE OF REVIEW: Primary Sjogren's syndrome is a systemic autoimmune disease
      whose clinical spectrum extends from sicca syndrome to systemic involvement
      (extraglandular manifestations). Recent reports have focused on expanding the
      clinical characterization and improving the diagnostic and therapeutic management
      of systemic Sjogren's. RECENT FINDINGS: The development of the EULAR-SS disease
      activity index represents a step forward in the evaluation of systemic Sjogren's,
      and three multicenter studies including more than 2500 European patients have
      confirmed that primary Sjogren's syndrome is, undeniably, a systemic autoimmune
      disease. Systemic involvement plays a key role in the prognosis of primary
      Sjogren's syndrome, and recent studies have focused on cutaneous, pulmonary,
      renal and neurological disease features. Other studies comparing the two sets of
      Sjogren's syndrome criteria (American College of Rheumatology vs. American
      European Consensus Group) in real-life patients found a moderate level of
      agreement. Autoantibodies are clues to an early diagnosis, as positivity confirms
      an autoimmune origin of the sicca syndrome and may appear several years before
      the disease diagnosis. In patients with a high clinical suspicion and negative
      results for the standard determination of anti-Ro/SS-A antibodies, specific
      detection of anti-Ro52/60 antibodies is recommended. Direct and indirect B-cell
      blocking seems to be the most promising biological pathway in primary Sjogren's
      syndrome, especially for systemic involvement, although a large controlled trial
      has failed to demonstrate the efficacy of rituximab for nonsystemic
      symptomatology (dryness, fatigue and pain). SUMMARY: Dryness of the mucosal
      surfaces is the pivotal, but not only, clinical involvement that characterizes
      primary Sjogren's syndrome. There is growing interest in and knowledge of the
      clinical characterization and therapeutic management of systemic Sjogren's.

PMID- 25050926
TI  - Biomarkers in systemic juvenile idiopathic arthritis: a comparison with
      biomarkers in cryopyrin-associated periodic syndromes.
AB  - PURPOSE OF REVIEW: This review summarizes biomarkers in systemic juvenile
      idiopathic arthritis (sJIA). Broadly, the markers are classified under protein,
      cellular, gene expression and genetic markers. We also compare the biomarkers in
      sJIA to biomarkers in cryopyrin-associated periodic syndrome (CAPS). RECENT
      FINDINGS: Recent publications showing the similarity of clinical response of sJIA
      and CAPS to anti-interleukin 1 therapies prompted a comparison at the biomarker
      level. SUMMARY: sJIA traditionally is classified under the umbrella of juvenile
      idiopathic arthritis. At the clinical phenotypic level, sJIA has several features
      that are more similar to those seen in CAPS. In this review, we summarize
      biomarkers in sJIA and CAPS and draw upon the various similarities and
      differences between the two families of diseases. The main differences between
      sJIA and CAPS biomarkers are genetic markers, with CAPS being a family of
      monogenic diseases with mutations in NLRP3. There have been a small number of
      publications describing cellular biomarkers in sJIA with no such studies
      described for CAPS. Many of the protein marker's characteristics of sJIA are also
      seen to characterize CAPS. The gene expression data in both sJIA and CAPS show a
      strong upregulation of innate immunity pathways. In addition, we describe a
      strong similarity between sJIA and CAPS at the gene expression level in which
      several genes that form a part of the erythropoiesis signature are upregulated in
      both sJIA and CAPS.

PMID- 25050927
TI  - Long term follow up of celiac disease-is atherosclerosis a problem?
AB  - Celiac disease (CD) is a lifelong condition and it often involves impaired
      nutrition, wide spectrum of symptoms and it requires constant dietetic treatment.
      The impact of the gluten-free diet on patients' nutritional status and on the
      other biochemical parameters is being widely investigated. In this article we
      looked into particular risk factors that might lead to increased prevalence of
      atherosclerosis in CD patients, including nutritional status, gluten-free diet,
      lipids profile and concomitant disease-type 1 diabetes mellitus. Here, we present
      the current data and research on these risk factors of atherosclerosis with
      respect to celiac disease. 

PMID- 25050928
TI  - Phylogeography of Cuban Rivulus: evidence for allopatric speciation and secondary
      dispersal across a marine barrier.
AB  - The genus Rivulus is currently comprised of two species, R. cylindraceus and R.
      insulaepinorum, which are endemic to Cuba. However, the taxonomic status of the
      latter species remains dubious because of the poor quality of the original
      description. In addition, a recent barcoding survey suggests that the two species
      may be conspecific. The aim of this study was to test the hypothesis that the two
      species represent a single evolutionary clade. To delimit the species and their
      evolutionary history, we used a combination of molecular phylogenetic analyses,
      with both mitochondrial and nuclear sequences, tests of phylogeographic
      hypotheses, combined with morphological measurements and information on known
      dispersal barriers and species distribution. None of the data sets support R.
      insulaepinorum and R. cylindraceus as separate taxa. However, a new species,
      restricted to the northwestern part of the main island, was identified by
      phylogenetic analyses, body colour pattern and geographical distribution. The
      evolutionary distance between the two lineages (cytb, d=15%; CAM-4, d=2.5%)
      indicates a long period of divergence. Phylogeographic analyses shed light on the
      dispersal history of R. cylindraceus, which probably originated on the Isla de la
      Juventud. They also suggest that each lineage had contrasting histories; Rivulus
      sp. is restricted to a relatively small geographic area whereas R. cylindraceus
      has dispersed considerably and more than once from its centre of origin, probably
      facilitated by sea level fluctuations. These results strengthen previous
      findings, i.e. that the diversity of Cuban freshwater fishes is far from well
      known and deserves more in-depth studies, and that vicariance and dispersal
      events have resulted in a complex biogeographical landscape which has had a
      significant impact on the freshwater fishes of the Caribbean islands. 

PMID- 25050929
TI  - Identification of a DNA methylome profile of esophageal squamous cell carcinoma
      and potential plasma epigenetic biomarkers for early diagnosis.
AB  - DNA methylation is a critical epigenetic mechanism involved in key cellular
      processes. Its deregulation has been linked to many human cancers including
      esophageal squamous cell carcinoma (ESCC). This study was designed to explore the
      whole methylation status of ESCC and to identify potential plasma biomarkers for
      early diagnosis. We used Infinium Methylation 450k array to analyze ESCC tissues
      (n = 4), paired normal surrounding tissues (n = 4) and normal mucosa from healthy
      individuals (n = 4), and combined these with gene expression data from the GEO
      database. One hundred and sixty eight genes had differentially methylated CpG
      sites in their promoter region and a gene expression pattern inverse to the
      direction of change in DNA methylation. These genes were involved in several
      cancer-related pathways. Three genes were validated in additional 42 ESCC tissues
      and paired normal surrounding tissues. The methylation frequency of EPB41L3,
      GPX3, and COL14A1 were higher in tumor tissues than in normal surrounding tissues
      (P < 0.017). The higher methylation frequency of EPB41l3 was correlated with
      large tumor size (P = 0.044) and advanced pT tumor stage (P = 0.001). The higher
      methylation frequency of GPX3 and COL14A1 were correlated with advanced pN tumor
      stage (P = 0.001 and P < 0.001). The methylation of EPB41L3, GPX3, and COL14A1
      genes were only found in ESCC patients' plasma, but not in normal individuals
      upon testing 42 ESCC patients and 50 healthy individuals. Diagnostic sensitivity
      was increased when methylation of any of the 3 genes were counted (64.3%
      sensitivity and 100% specificity). These differentially methylated genes in
      plasma may be used as biomarkers for early diagnosis of ESCC.

PMID- 25050931
TI  - Abnormal cerebellar development and Purkinje cell defects in Lgl1-Pax2
      conditional knockout mice.
AB  - Lgl1 was initially identified as a tumour suppressor in flies and is
      characterised as a key regulator of epithelial polarity and asymmetric cell
      division. A previous study indicated that More-Cre-mediated Lgl1 knockout mice
      exhibited significant brain dysplasia and died within 24h after birth. To
      overcome early neonatal lethality, we generated Lgl1 conditional knockout mice
      mediated by Pax2-Cre, which is expressed in almost all cells in the cerebellum,
      and we examined the functions of Lgl1 in the cerebellum. Impaired motor
      coordination was detected in the mutant mice. Consistent with this abnormal
      behaviour, homozygous mice possessed a smaller cerebellum with fewer lobes,
      reduced granule precursor cell (GPC) proliferation, decreased Purkinje cell (PC)
      quantity and dendritic dysplasia. Loss of Lgl1 in the cerebellum led to
      hyperproliferation and impaired differentiation of neural progenitors in
      ventricular zone. Based on the TUNEL assay, we observed increased apoptosis in
      the cerebellum of mutant mice. We proposed that impaired differentiation and
      increased apoptosis may contribute to decreased PC quantity. To clarify the
      effect of Lgl1 on cerebellar granule cells, we used Math1-Cre to specifically
      delete Lgl1 in granule cells. Interestingly, the Lgl1-Math1 conditional knockout
      mice exhibited normal proliferation of GPCs and cerebellar development. Thus, we
      speculated that the reduction in the proliferation of GPCs in Lgl1-Pax2
      conditional knockout mice may be secondary to the decreased number of PCs, which
      secrete the mitogenic factor Sonic hedgehog to regulate GPC proliferation. Taken
      together, these findings suggest that Lgl1 plays a key role in cerebellar
      development and folia formation by regulating the development of PCs. 

PMID- 25050930
TI  - Specification of the mouse cardiac conduction system in the absence of Endothelin
      signaling.
AB  - Coordinated contraction of the heart is essential for survival and is regulated
      by the cardiac conduction system. Contraction of ventricular myocytes is
      controlled by the terminal part of the conduction system known as the Purkinje
      fiber network. Lineage analyses in chickens and mice have established that the
      Purkinje fibers of the peripheral ventricular conduction system arise from
      working myocytes during cardiac development. It has been proposed, based
      primarily on gain-of-function studies, that Endothelin signaling is responsible
      for myocyte-to-Purkinje fiber transdifferentiation during avian heart
      development. However, the role of Endothelin signaling in mammalian conduction
      system development is less clear, and the development of the cardiac conduction
      system in mice lacking Endothelin signaling has not been previously addressed.
      Here, we assessed the specification of the cardiac conduction system in mouse
      embryos lacking all Endothelin signaling. We found that mouse embryos that were
      homozygous null for both ednra and ednrb, the genes encoding the two Endothelin
      receptors in mice, were born at predicted Mendelian frequency and had normal
      specification of the cardiac conduction system and apparently normal
      electrocardiograms with normal QRS intervals. In addition, we found that ednra
      expression within the heart was restricted to the myocardium while ednrb
      expression in the heart was restricted to the endocardium and coronary
      endothelium. By establishing that ednra and ednrb are expressed in distinct
      compartments within the developing mammalian heart and that Endothelin signaling
      is dispensable for specification and function of the cardiac conduction system,
      this work has important implications for our understanding of mammalian cardiac
      development. 

PMID- 25050932
TI  - The dystroglycan: nestled in an adhesome during embryonic development.
AB  - Invertebrate and vertebrate development relies on complex processes that require
      many coordinated cell functions including cell adhesion, migration, proliferation
      and polarization. These processes depend on tissues and are spatio-temporally
      regulated by specific interactions between cells and between cells and the
      extracellular matrices. The dystroglycan, a transmembrane receptor that binds
      multiple extracellular matrix proteins, is expressed from oogenesis to
      organogenesis. There are increasing data suggesting that the axis, consisting of
      extracellular component-dystroglycan-cytoplasmic proteins, controls both the
      adhesion of cells to matrices as well as the transduction of signals coming from
      or directed to matrices. In this article, we review current advances leading to
      consider that the dystroglycan is a key protein nestled in an adhesome involved
      in mechanisms of cell adhesion during embryonic development. 

PMID- 25050933
TI  - Identification of genes driving lineage divergence from single-cell gene
      expression data in C. elegans.
AB  - The nematode Caenorhabditis elegans (C. elegans) is an ideal model organism to
      study the cell fate specification mechanisms during embryogenesis. It is
      generally believed that cell fate specification in C. elegans is mainly mediated
      by lineage-based mechanisms, where the specification paths are driven forward by
      a succession of asymmetric cell divisions. However, little is known about how
      each binary decision is made by gene regulatory programs. In this study, we
      endeavor to obtain a global understanding of cell lineage/fate divergence
      processes during the early embryogenesis of C. elegans. We reanalyzed the EPIC
      data set, which traced the expression level of reporter genes at single-cell
      resolution on a nearly continuous time scale up to the 350-cell stage in C.
      elegans embryos. We examined the expression patterns for a total of 131 genes
      from 287 embryos with high quality image recordings, among which 86 genes have
      replicate embryos. Our results reveal that during early embryogenesis, divergence
      between sister lineages could be largely explained by a few genes. We predicted
      genes driving lineage divergence and explored their expression patterns in sister
      lineages. Moreover, we found that divisions leading to fate divergence are
      associated with a large number of genes being differentially expressed between
      sister lineages. Interestingly, we found that the developmental paths of lineages
      could be differentiated by a small set of genes. Therefore, our results support
      the notion that the cell fate patterns in C. elegans are achieved through
      stepwise binary decisions punctuated by cell divisions. Our predicted genes
      driving lineage divergence provide good starting points for future detailed
      characterization of their roles in the embryogenesis in this important model
      organism. 

PMID- 25050934
TI  - Synthesis and characterization of two quaternary uranium tellurides, RbTiU3Te9
      and CsTiU3Te9.
AB  - Black crystals of RbTiU3Te9 and CsTiU3Te9 have been synthesized at 1223 and 1173
      K, respectively, by high-temperature solid-state routes. These compounds
      crystallize in a new structure type in space group C(2h)2-P21/m of the monoclinic
      system. The structure, which is similar to that of CsTiUTe5, consists of UTe2
      layers connected into a three-dimensional framework by TiTe6 octahedra. The
      expanded UTe2 layers leave channels that are filled by Rb or Cs atoms. Single
      crystal resistivity measurements on CsTiU3Te9 are consistent with semiconducting
      behavior; the calculated activation energy is 0.30(1) eV. X-ray photoelectron
      spectroscopic measurements on CsTiU3Te9 indicate that the compound contains U4+.
      From single-crystal magnetic measurements, CsTiU3Te9 is consistent with
      antiferromagnetic coupling between magnetic U atoms. The very low value of the
      effective magnetic moment of 0.56(2) MU(B) is believed to arise from a
      coexistence of magnetic and nonmagnetic U atoms.

PMID- 25050935
TI  - Testosterone is associated with the cardiovascular autonomic response to a
      stressor in healthy men.
AB  - OBJECTIVE: Men have high cardiovascular risk and unfavourable cardiac autonomic
      tone compared to premenopausal women. The role of sex hormones in control of
      autonomic tone is unclear. We sought to determine the association between sex
      hormones and cardiosympathovagal tone at baseline and in response to a
      physiological stressor. METHODS: Forty-eight healthy subjects (21 men, 27
      premenopausal women) were studied in high-salt balance. Cardiac autonomic tone
      was assessed by heart rate variability, calculated by spectral power analysis
      (low frequency (LF, a measure of sympathetic modulation), high frequency (HF, a
      measure of vagal modulation) and LF:HF (a measure of cardiosympathovagal
      balance)) at baseline and in response to graded Angiotensin II (AngII) infusion
      (3 ng/kg/min * 30 min, 6 ng/kg/min * 30 min) were measured. The primary outcome
      was association between endogenous sex hormone levels and measures of cardiac
      autonomic tone. RESULTS: All subjects had sex hormone levels in the normal range.
      No associations were observed between sex hormones and baseline cardiac autonomic
      tone in men or women. Men with lower testosterone levels, however, were unable to
      maintain both cardiosympathetic (p = 0.045) and cardiovagal tone (p = 0.035) in
      response to AngII even after adjustments for covariates. No association was
      observed between estradiol and progesterone and cardiac autonomic response to
      AngII in either sex. CONCLUSION: An unfavourable shift in the cardiac autonomic
      tone in men with lower testosterone levels was observed in response to a
      stressor. Understanding the role of sex hormones in modulation of cardiac
      autonomic tone may help guide risk reduction strategies in men.

PMID- 25050937
TI  - Geochemical control on uranium(IV) mobility in a mining-impacted wetland.
AB  - Wetlands often act as sinks for uranium and other trace elements. Our previous
      work at a mining-impacted wetland in France showed that a labile noncrystalline
      U(IV) species consisting of U(IV) bound to Al-P-Fe-Si aggregates was predominant
      in the soil at locations exhibiting a U-containing clay-rich layer within the top
      30 cm. Additionally, in the porewater, the association of U(IV) with Fe(II) and
      organic matter colloids significantly increased U(IV) mobility in the wetland. In
      the present study, within the same wetland, we further demonstrate that the
      speciation of U at a location not impacted by the clay-rich layer is a different
      noncrystalline U(IV) species, consisting of U(IV) bound to organic matter in
      soil. We also show that the clay-poor location includes an abundant sulfate
      supply and active microbial sulfate reduction that induce substantial pyrite
      (FeS2) precipitation. As a result, Fe(II) concentrations in the porewater are
      much lower than those at clay-impacted zones. U porewater concentrations (0.02
      0.26 MUM) are also considerably lower than those at the clay-impacted locations
      (0.21-3.4 MUM) resulting in minimal U mobility. In both cases, soil-associated U
      represents more than 99% of U in the wetland. We conclude that the low U mobility
      reported at clay-poor locations is due to the limited association of Fe(II) with
      organic matter colloids in porewater and/or higher stability of the
      noncrystalline U(IV) species in soil at those locations. 

PMID- 25050938
TI  - Combination of transient 2D-IR experiments and ab initio computations sheds light
      on the formation of the charge-transfer state in photoexcited carbonyl
      carotenoids.
AB  - The excited state dynamics of carbonyl carotenoids is very complex because of the
      coupling of single- and doubly excited states and the possible involvement of
      intramolecular charge-transfer (ICT) states. In this contribution we employ
      ultrafast infrared spectroscopy and theoretical computations to investigate the
      relaxation dynamics of trans-8'-apo-beta-carotenal occurring on the picosecond
      time scale, after excitation in the S2 state. In a (slightly) polar solvent like
      chloroform, one-dimensional (T1D-IR) and two-dimensional (T2D-IR) transient
      infrared spectroscopy reveal spectral components with characteristic frequencies
      and lifetimes that are not observed in nonpolar solvents (cyclohexane). Combining
      experimental evidence with an analysis of CASPT2//CASSCF ground and excited state
      minima and energy profiles, complemented with TDDFT calculations in gas phase and
      in solvent, we propose a photochemical decay mechanism for this system where only
      the bright single-excited 1Bu(+) and the dark double-excited 2Ag(-) states are
      involved. Specifically, the initially populated 1Bu(+) relaxes toward 2Ag(-) in
      200 fs. In a nonpolar solvent 2Ag(-) decays to the ground state (GS) in 25 ps. In
      polar solvents, distortions along twisting modes of the chain promote a
      repopulation of the 1Bu(+) state which then quickly relaxes to the GS (18 ps in
      chloroform). The 1Bu(+) state has a high electric dipole and is the main
      contributor to the charge-transfer state involved in the dynamics in polar
      solvents. The 2Ag(-) -> 1Bu(+) population transfer is evidenced by a cross peak
      on the T2D-IR map revealing that the motions along the same stretching of the
      conjugated chain on the 2Ag(-) and 1Bu(+) states are coupled. 

PMID- 25050936
TI  - Rapid rebound of the Treg compartment in DEREG mice limits the impact of Treg
      depletion on mycobacterial burden, but prevents autoimmunity.
AB  - The development of an effective vaccine against tuberculosis (Tb) represents one
      of the major medical challenges of this century. Mycobacterium bovis Bacille
      Calmette-Guerin (BCG), the only vaccine available at present, is mostly effective
      at preventing disseminated Tb in children, but shows variable protection against
      pulmonary Tb, the most common form in adults. The reasons for this poor efficacy
      are not completely understood, but there is evidence that T regulatory cells
      (Tregs) might be involved. Similarly, Tregs have been associated with the
      immunosuppression observed in patients infected with Tb and are therefore
      believed to play a role in pathogen persistence. Thus, Treg depletion has been
      postulated as a novel strategy to potentiate M. bovis BCG vaccination on one
      side, while on the other, employed as a therapeutic approach during chronic Tb
      infection. Yet since Tregs are critically involved in controlling autoimmune
      inflammation, elimination of Tregs may therefore also incur the danger of an
      excessive inflammatory immune response. Thus, understanding the dynamics and
      function of Tregs during mycobacterial infection is crucial to evaluate the
      potential of Treg depletion as a medical option. To address this, we depleted
      Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb) using
      DEREG mice, which express the diphtheria toxin (DT) receptor under the control of
      the FoxP3 locus, thereby allowing the selective depletion of FoxP3+ Tregs. Our
      results show that after depletion, the Treg niche is rapidly refilled by a
      population of DT-insensitive Tregs (diTregs) and bacterial load remains
      unchanged. On the contrary, impaired rebound of Tregs in DEREG * FoxP3GFP mice
      improves pathogen burden, but is accompanied by detrimental autoimmune
      inflammation. Therefore, our study provides the proof-of-principle that, although
      a high degree of Treg depletion may contribute to the control of mycobacterial
      infection, it carries the risk of autoimmunity. 

PMID- 25050939
TI  - Identification of chemical compounds present in different fractions of Annona
      reticulata L. leaf by using GC-MS.
AB  - GC-MS analysis of fractions prepared from hydro-alcoholic extract of Annona
      reticulata Linn (Family Annonaceae) leaf revealed the presence of 9,10
      dimethyltricyclo[4.2.1.1(2,5)]decane-9,10-diol; 4-(1,5-dihydroxy-2,6,6
      trimethylcyclohex-2-enyl)but-3-en-2-one; 3,7-dimethyl-6-nonen-1-ol acetate; 9
      octadecenamide,(Z)-; glycerine; D-glucose,6-O-alpha-D-galactopyranosyl-;
      desulphosinigrin and alpha-methyl-D-mannopyranoside as few of the major compounds
      in different fractions. The presence of these compounds in the plant has been
      identified for the first time.

PMID- 25050941
TI  - GMM-based intermediate matching kernel for classification of varying length
      patterns of long duration speech using support vector machines.
AB  - Dynamic kernel (DK)-based support vector machines are used for the classification
      of varying length patterns. This paper explores the use of intermediate matching
      kernel (IMK) as a DK for classification of varying length patterns of long
      duration speech represented as sets of feature vectors. The main issue in
      construction of IMK is the choice for the set of virtual feature vectors used to
      select the local feature vectors for matching. This paper proposes to use
      components of class-independent Gaussian mixture model (CIGMM) as a
      representation for the set of virtual feature vectors. For every component of
      CIGMM, a local feature vector each from the two sets of local feature vectors
      that has the highest probability of belonging to that component is selected and a
      base kernel is computed between the selected local feature vectors. The IMK is
      computed as the sum of all the base kernels corresponding to different components
      of CIGMM. It is proposed to use the responsibility term weighted base kernels in
      computation of IMK to improve its discrimination ability. This paper also
      proposes the posterior probability weighted DKs (including the proposed IMKs) to
      improve their classification performance and reduce the number of support
      vectors. The performance of the support vector machine (SVM)-based classifiers
      using the proposed IMKs is studied for speech emotion recognition and speaker
      identification tasks and compared with that of the SVM-based classifiers using
      the state-of-the-art DKs. 

PMID- 25050940
TI  - Hubs and authorities in the world trade network using a weighted HITS algorithm.
AB  - We investigate the economic hubs and authorities of the world trade network (WTN)
      from 1992 to 2012, an era of rapid economic globalization. Using a well-defined
      weighted hyperlink-induced topic search (HITS) algorithm, we can calculate the
      values of the weighted HITS hub and authority for each country in a conjugate
      way. In the context of the WTN, authority values are large for countries with
      significant imports from large hub countries, and hub values are large for
      countries with significant exports to high-authority countries. The United States
      was the largest economic authority in the WTN from 1992 to 2012. The authority
      value of the United States has declined since 2001, and China has now become the
      largest hub in the WTN. At the same time, China's authority value has grown as
      China is transforming itself from the "factory of the world" to the "market of
      the world." European countries show a tendency to trade mostly within the
      European Union, which has decreased Europe's hub and authority values. Japan's
      authority value has increased slowly, while its hub value has declined. These
      changes are consistent with Japan's transition from being an export-driven
      economy in its high economic growth era in the latter half of the twentieth
      century to being a more mature, economically balanced nation.

PMID- 25050942
TI  - Extensions of kmeans-type algorithms: a new clustering framework by integrating
      intracluster compactness and intercluster separation.
AB  - Kmeans-type clustering aims at partitioning a data set into clusters such that
      the objects in a cluster are compact and the objects in different clusters are
      well separated. However, most kmeans-type clustering algorithms rely on only
      intracluster compactness while overlooking intercluster separation. In this
      paper, a series of new clustering algorithms by extending the existing kmeans
      type algorithms is proposed by integrating both intracluster compactness and
      intercluster separation. First, a set of new objective functions for clustering
      is developed. Based on these objective functions, the corresponding updating
      rules for the algorithms are then derived analytically. The properties and
      performances of these algorithms are investigated on several synthetic and real
      life data sets. Experimental studies demonstrate that our proposed algorithms
      outperform the state-of-the-art kmeans-type clustering algorithms with respect to
      four metrics: accuracy, RandIndex, Fscore, and normal mutual information. 

PMID- 25050943
TI  - Efficient kernel sparse coding via first-order smooth optimization.
AB  - We consider the problem of dictionary learning and sparse coding, where the task
      is to find a concise set of basis vectors that accurately represent the
      observation data with only small numbers of active bases. Typically formulated as
      an L1-regularized least-squares problem, the problem incurs computational
      difficulty originating from the nondifferentiable objective. Recent approaches to
      sparse coding thus have mainly focused on acceleration of the learning algorithm.
      In this paper, we propose an even more efficient and scalable sparse coding
      algorithm based on the first-order smooth optimization technique. The algorithm
      finds the theoretically guaranteed optimal sparse codes of the epsilon
      approximate problem in a series of optimization subproblems, where each
      subproblem admits analytic solution, hence very fast and scalable with large
      scale data. We further extend it to nonlinear sparse coding using kernel trick by
      showing that the representer theorem holds for the kernel sparse coding problem.
      This allows us to apply dual optimization, which essentially results in the same
      linear sparse coding problem in dual variables, highly beneficial compared with
      the existing methods that suffer from local minima and restricted forms of kernel
      function. The efficiency of our algorithms is demonstrated for natural stimuli
      data sets and several image classification problems. 

PMID- 25050944
TI  - Contact-force distribution optimization and control for quadruped robots using
      both gradient and adaptive neural networks.
AB  - This paper investigates optimal feet forces' distribution and control of
      quadruped robots under external disturbance forces. First, we formulate a
      constrained dynamics of quadruped robots and derive a reduced-order dynamical
      model of motion/force. Consider an external wrench on quadruped robots; the
      distribution of required forces and moments on the supporting legs of a quadruped
      robot is handled as a tip-point force distribution and used to equilibrate the
      external wrench. Then, a gradient neural network is adopted to deal with the
      optimized objective function formulated as to minimize this quadratic objective
      function subjected to linear equality and inequality constraints. For the
      obtained optimized tip-point force and the motion of legs, we propose the hybrid
      motion/force control based on an adaptive neural network to compensate for the
      perturbations in the environment and approximate feedforward force and impedance
      of the leg joints. The proposed control can confront the uncertainties including
      approximation error and external perturbation. The verification of the proposed
      control is conducted using a simulation. 

PMID- 25050945
TI  - On the capabilities and computational costs of neuron models.
AB  - We review the Hodgkin-Huxley, Izhikevich, and leaky integrate-and-fire neuron
      models in regular spiking modes solved with the forward Euler, fourth-order Runge
      Kutta, and exponential Euler methods and determine the necessary time steps and
      corresponding computational costs required to make the solutions accurate. We
      conclude that the leaky integrate-and-fire needs the least number of
      computations, and that the Hodgkin-Huxley and Izhikevich models are comparable in
      computational cost. 

PMID- 25050946
TI  - Global sensitivity analysis approach for input selection and system
      identification purposes--a new framework for feedforward neural networks.
AB  - A new algorithm for the selection of input variables of neural network is
      proposed. This new method, applied after the training stage, ranks the inputs
      according to their importance in the variance of the model output. The use of a
      global sensitivity analysis technique, extended Fourier amplitude sensitivity
      test, gives the total sensitivity index for each variable, which allows for the
      ranking and the removal of the less relevant inputs. Applied to some benchmarking
      problems in the field of features selection, the proposed approach shows good
      agreement in keeping the relevant variables. This new method is a useful tool for
      removing superfluous inputs and for system identification. 

PMID- 25050947
TI  - Cooperative tracking control of nonlinear multiagent systems using self
      structuring neural networks.
AB  - This paper considers a cooperative tracking problem for a group of nonlinear
      multiagent systems under a directed graph that characterizes the interaction
      between the leader and the followers. All the networked systems can have
      different dynamics and all the dynamics are unknown. A neural network (NN) with
      flexible structure is used to approximate the unknown dynamics at each node.
      Considering that the leader is a neighbor of only a subset of the followers and
      the followers have only local interactions, we introduce a cooperative dynamic
      observer at each node to overcome the deficiency of the traditional tracking
      control strategies. An observer-based cooperative controller design framework is
      proposed with the aid of graph tools, Lyapunov-based design method, self
      structuring NN, and separation principle. It is proved that each agent can follow
      the active leader only if the communication graph contains a spanning tree.
      Simulation results on networked robots are provided to show the effectiveness of
      the proposed control algorithms. 

PMID- 25050948
TI  - Distributed neural network control for adaptive synchronization of uncertain
      dynamical multiagent systems.
AB  - This paper addresses the leader-follower synchronization problem of uncertain
      dynamical multiagent systems with nonlinear dynamics. Distributed adaptive
      synchronization controllers are proposed based on the state information of
      neighboring agents. The control design is developed for both undirected and
      directed communication topologies without requiring the accurate model of each
      agent. This result is further extended to the output feedback case where a
      neighborhood observer is proposed based on relative output information of
      neighboring agents. Then, distributed observer-based synchronization controllers
      are derived and a parameter-dependent Riccati inequality is employed to prove the
      stability. This design has a favorable decouple property between the observer and
      the controller designs for nonlinear multiagent systems. For both cases, the
      developed controllers guarantee that the state of each agent synchronizes to that
      of the leader with bounded residual errors. Two illustrative examples validate
      the efficacy of the proposed methods. 

PMID- 25050949
TI  - Instance-level constraint-based semisupervised learning with imposed space
      partitioning.
AB  - A new method for semisupervised learning from pairwise sample (must- and cannot
      link) constraints is introduced. It addresses an important limitation of many
      existing methods, whose solutions do not achieve effective propagation of the
      constraint information to unconstrained samples. We overcome this limitation by
      constraining the solution to comport with a smooth (soft) class partition of the
      feature space, which necessarily entails constraint propagation and
      generalization to unconstrained samples. This is achieved via a parameterized
      mean-field approximation to the posterior distribution over component
      assignments, with the parameterization chosen to match the representation power
      of the chosen (generative) mixture density family. Unlike many existing methods,
      our method flexibly models classes using a variable number of components, which
      allows it to learn complex class boundaries. Also, unlike most of the methods,
      ours estimates the number of latent classes present in the data. Experiments on
      synthetic data and data sets from the UC Irvine machine learning repository show
      that, overall, our method achieves significant improvements in classification
      performance compared with the existing methods. 

PMID- 25050950
TI  - Modified principal component analysis: an integration of multiple similarity
      subspace models.
AB  - We modify the conventional principal component analysis (PCA) and propose a novel
      subspace learning framework, modified PCA (MPCA), using multiple similarity
      measurements. MPCA computes three similarity matrices exploiting the similarity
      measurements: 1) mutual information; 2) angle information; and 3) Gaussian kernel
      similarity. We employ the eigenvectors of similarity matrices to produce new
      subspaces, referred to as similarity subspaces. A new integrated similarity
      subspace is then generated using a novel feature selection approach. This
      approach needs to construct a kind of vector set, termed weak machine cell (WMC),
      which contains an appropriate number of the eigenvectors spanning the similarity
      subspaces. Combining the wrapper method and the forward selection scheme, MPCA
      selects a WMC at a time that has a powerful discriminative capability to classify
      samples. MPCA is very suitable for the application scenarios in which the number
      of the training samples is less than the data dimensionality. MPCA outperforms
      the other state-of-the-art PCA-based methods in terms of both classification
      accuracy and clustering result. In addition, MPCA can be applied to face image
      reconstruction. MPCA can use other types of similarity measurements. Extensive
      experiments on many popular real-world data sets, such as face databases, show
      that MPCA achieves desirable classification results, as well as has a powerful
      capability to represent data. 

PMID- 25050951
TI  - On the complexity of neural network classifiers: a comparison between shallow and
      deep architectures.
AB  - Recently, researchers in the artificial neural network field have focused their
      attention on connectionist models composed by several hidden layers. In fact,
      experimental results and heuristic considerations suggest that deep architectures
      are more suitable than shallow ones for modern applications, facing very complex
      problems, e.g., vision and human language understanding. However, the actual
      theoretical results supporting such a claim are still few and incomplete. In this
      paper, we propose a new approach to study how the depth of feedforward neural
      networks impacts on their ability in implementing high complexity functions.
      First, a new measure based on topological concepts is introduced, aimed at
      evaluating the complexity of the function implemented by a neural network, used
      for classification purposes. Then, deep and shallow neural architectures with
      common sigmoidal activation functions are compared, by deriving upper and lower
      bounds on their complexity, and studying how the complexity depends on the number
      of hidden units and the used activation function. The obtained results seem to
      support the idea that deep networks actually implements functions of higher
      complexity, so that they are able, with the same number of resources, to address
      more difficult problems. 

PMID- 25050952
TI  - A minimum resource neural network framework for solving multiconstraint shortest
      path problems.
AB  - Characterized by using minimum hard (structural) and soft (computational)
      resources, a novel parameter-free minimal resource neural network (MRNN)
      framework is proposed for solving a wide range of single-source shortest path
      (SP) problems for various graph types. The problems are the k-shortest time path
      problems with any combination of three constraints: time, hop, and label
      constraints, and the graphs can be directed, undirected, or bidirected with
      symmetric and/or asymmetric traversal time, which can be real and time dependent.
      Isomorphic to the graph where the SP is to be sought, the network is activated by
      generating autowave at source neuron and the autowave travels automatically along
      the paths with the speed of a hop in an iteration. Properties of the network are
      studied, algorithms are presented, and computation complexity is analyzed. The
      framework guarantees globally optimal solutions of a series of problems during
      the iteration process of the network, which provides insight into why even the SP
      is still too long to be satisfied. The network facilitates very large scale
      integrated circuit implementation and adapt to very large scale problems due to
      its massively parallel processing and minimum resource utilization. When
      implemented in a sequentially processing computer, experiments on synthetic
      graphs, road maps of cities of the USA, and vehicle routing with time windows
      indicate that the MRNN is especially efficient for large scale sparse graphs and
      even dense graphs with some constraints, e.g., the CPU time taken and the
      iteration number used for the road maps of cities of the USA is even less than  ~
      2% and 0.5% that of the Dijkstra's algorithm. 

PMID- 25050953
TI  - Simulating dynamic plastic continuous neural networks by finite elements.
AB  - We introduce dynamic plastic continuous neural network (DPCNN), which is
      comprised of neurons distributed in a nonlinear plastic medium where wire-like
      connections of neural networks are replaced with the continuous medium. We use
      finite element method to model the dynamic phenomenon of information processing
      within the DPCNNs. During the training, instead of weights, the properties of the
      continuous material at its different locations and some properties of neurons are
      modified. Input and output can be vectors and/or continuous functions over lines
      and/or areas. Delay and feedback from neurons to themselves and from outputs
      occur in the DPCNNs. We model a simple form of the DPCNN where the medium is a
      rectangular plate of bilinear material, and the neurons continuously fire a
      signal, which is a function of the horizontal displacement. 

PMID- 25050954
TI  - Minimizing nearest neighbor classification error for nonparametric dimension
      reduction.
AB  - In this brief, we show that minimizing nearest neighbor classification error
      (MNNE) is a favorable criterion for supervised linear dimension reduction (SLDR).
      We prove that MNNE is better than maximizing mutual information in the sense of
      being a proxy of the Bayes optimal criterion. Based on kernel density estimation,
      we derive a nonparametric algorithm for MNNE. Experiments on benchmark data sets
      show the superiority of MNNE over existing nonparametric SLDR methods. 

PMID- 25050955
TI  - P granules.

PMID- 25050956
TI  - Marine mammals trace anthropogenic structures at sea.

PMID- 25050957
TI  - Aphid gene of bacterial origin encodes a protein transported to an obligate
      endosymbiont.

PMID- 25050958
TI  - Palaeontology: Chinese amber insects bridge the gap.
AB  - n the study of fossil insects, Chinese amber from Fushun has been largely
      overlooked. A new study now reveals a highly diverse biota and provides a wealth
      of new information on the past Asian insect fauna.

PMID- 25050959
TI  - Hippocampal neurons: simulating the spatial structure of a complex maze.
AB  - Hippocampal place neurons not only represent current location, but fire in
      sequences that appear to simulate past and future spatial trajectories. A recent
      study has found that the firing sequences match the structure of a complex maze,
      suggesting that the structure of the environment is encoded by the place system,
      perhaps to aid navigational planning. 

PMID- 25050960
TI  - Ape gestures: interpreting chimpanzee and bonobo minds.
AB  - Improving methods for studying primate interaction are providing new insights
      into the relationship between gesture and meaning in chimpanzee and bonobo
      communication. 

PMID- 25050961
TI  - Docking interactions: cell-cycle regulation and beyond.
AB  - In budding yeast, the mating pathway activates Far1 to inhibit G1 cyclins in
      complex with the cyclin-dependent kinase (Cln-Cdk). Yet, the molecular mechanism
      has remained largely unclear for over 20 years. A recent report helps shed light
      on this regulation. 

PMID- 25050962
TI  - Coevolution: puff pollination in tropical flowers.
AB  - A new study shows that birds plucking anthers of the Melastome, Axinaea,
      demonstrate a novel bird pollination mechanism. Each stamen of Axinaea offers a
      nutrient-rich, berry-like food body that, when bitten, releases a puff of pollen
      allowing transfer to stigmas by wind or the pollen-dusted bird.

PMID- 25050963
TI  - Centrosome duplication: suspending a license by phosphorylating a template.
AB  - The phosphorylation status of Sfi1, a structural component of the yeast
      centrosome, governs the centrosome duplication cycle, raising the possibility
      that licensing of centrosome duplication occurs by modulating Sfi1, which
      potentially acts as a template for a new centrosome. 

PMID- 25050964
TI  - Endosymbiosis: protein targeting further erodes the organelle/symbiont
      distinction.
AB  - New work in aphids shows that a nuclear-encoded protein resulting from a
      horizontal gene transfer is targeted to a bacterial symbiont, further blurring
      the distinction between organelle and symbiont. 

PMID- 25050965
TI  - Animal evolution: looking for the first nervous system.
AB  - The human brain is easily the most baffling bit of biology on the planet. How did
      the nervous system evolve? What came first: neurons or synaptic proteins? A new
      paper studying the pancake-shaped Trichoplax suggests it was not the neurons. 

PMID- 25050966
TI  - Tumor models: tumor-stroma interactions drive neoplastic transformation in
      Drosophila.
AB  - Stromal cells play a supportive role in the initiation and progression of
      carcinomas. A new study in Drosophila implicates mesenchymal cells in supporting
      EGF receptor-driven tumor growth and cellular transformation of epithelial
      tissues. 

PMID- 25050968
TI  - Testing usability and trainability of indirect touch interaction: perspective for
      the next generation of air traffic control systems.
AB  - This study aims to determine whether indirect touch device can be used to
      interact with graphical objects displayed on another screen in an air traffic
      control (ATC) context. The introduction of such a device likely requires an
      adaptation of the sensory-motor system. The operator has to simultaneously
      perform movements on the horizontal plane while assessing them on the vertical
      plane. Thirty-six right-handed participants performed movement training with
      either constant or variable practice and with or without visual feedback of the
      displacement of their actions. Participants then performed a test phase without
      visual feedback. Performance improved in both practice conditions, but accuracy
      was higher with visual feedback. During the test phase, movement time was longer
      for those who had practiced with feedback, suggesting an element of dependency.
      However, this 'cost' of feedback did not extend to movement accuracy. Finally,
      participants who had received variable training performed better in the test
      phase, but accuracy was still unsatisfactory. We conclude that continuous visual
      feedback on the stylus position is necessary if tablets are to be introduced in
      ATC. 

PMID- 25050969
TI  - Unusual synergistic effects upon incorporation of Fe and/or Ni into mesoporous
      Co3O4 for enhanced oxygen evolution.
AB  - Fe and Ni doped mesoporous Co3O4 (mCo3O4) catalysts were prepared and
      investigated for electrochemical oxygen evolution. The incorporation of Fe into
      mCo3O4 (Fe-mCo3O4) results in unusual synergistic effects via destruction of the
      bulk mesoporous structure and formation of slit-like pores. The Fe-mCo3O4
      composite displayed a significantly enhanced catalytic activity for oxygen
      evolution. 

PMID- 25050967
TI  - Connecting the cytoskeleton to the endoplasmic reticulum and Golgi.
AB  - A tendency in cell biology is to divide and conquer. For example, decades of
      painstaking work have led to an understanding of endoplasmic reticulum (ER) and
      Golgi structure, dynamics, and transport. In parallel, cytoskeletal researchers
      have revealed a fantastic diversity of structure and cellular function in both
      actin and microtubules. Increasingly, these areas overlap, necessitating an
      understanding of both organelle and cytoskeletal biology. This review addresses
      connections between the actin/microtubule cytoskeletons and organelles in animal
      cells, focusing on three key areas: ER structure and function; ER-to-Golgi
      transport; and Golgi structure and function. Making these connections has been
      challenging for several reasons: the small sizes and dynamic characteristics of
      some components; the fact that organelle-specific cytoskeletal elements can
      easily be obscured by more abundant cytoskeletal structures; and the difficulties
      in imaging membranes and cytoskeleton simultaneously, especially at the
      ultrastructural level. One major concept is that the cytoskeleton is frequently
      used to generate force for membrane movement, with two potential consequences:
      translocation of the organelle, or deformation of the organelle membrane. While
      initially discussing issues common to metazoan cells in general, we subsequently
      highlight specific features of neurons, since these highly polarized cells
      present unique challenges for organellar distribution and dynamics. 

PMID- 25050970
TI  - Efficacy of ciprofloxacin-clarithromycin combination against drug-resistant
      Pseudomonas aeruginosa mature biofilm using in vitro experimental model.
AB  - Pseudomonas aeruginosa is the main cause of mortality in cystic fibrosis patients
      and eradication of its biofilm represents a substantial problem clinically. In
      this study, biofilm of a cystic fibrosis strain P. aeruginosa PACI22 was
      established and confocal laser scanning microscopy was utilized for biofilm
      visualization. A quantitative time-kill biofilm model was implemented in vitro to
      assess the biocidal effect of ciprofloxacin, clarithromycin, and their
      combination at concentration levels ranged from 0.5* to 64* minimum biofilm
      inhibitory concentrations (MBIC) against the biofilm and the mean log bacterial
      densities (Log CFU/ml) retrieved from the biofilm were monitored by frequent
      sampling at 0, 3, 6, 9, 12, and 24 hr throughout the experiment. The results
      revealed that none of the tested antibiotics alone could completely eradicate the
      biofilm-ensconced bacteria at 0.5-64* MBIC values after 24 hr of treatment.
      Conversely, ciprofloxacin-clarithromycin combination at 32-64* MBIC entirely
      exterminated the biofilm. Furthermore, a substantial in vitro synergism between
      ciprofloxacin and clarithromycin against the biofilm was experimentally verified.
      This promising synergism affords scientific rationale for further in vivo
      investigations to evaluate the therapeutic potential of this combination for
      treatment of chronic pulmonary infections caused by P. aeruginosa biofilms.

PMID- 25050971
TI  - Influences of extracellular polymeric substances on the dewaterability of sewage
      sludge during bioleaching.
AB  - Extracellular polymeric substances (EPS) play important roles in regulating the
      dewaterability of sludge. This study sought to elucidate the influence of EPS on
      the dewaterability of sludge during bioleaching process. Results showed that, in
      bioleaching system with the co-inoculation of Acidithiobacillus thiooxidans TS6
      and Acidithiobacillus ferrooxidans LX5 (A. t+A. f system), the capillary suction
      time (CST) of sludge reduced from 255.9 s to 25.45 s within 48 h, which was
      obviously better than the controls. The correlation analysis between sludge CST
      and sludge EPS revealed that the sludge EPS significantly impacted the
      dewaterability of sludge. Sludge CST had correlation with protein content in
      slime and both protein and polysaccharide contents in TB-EPS and Slime+LB+TB
      layers, and the decrease of protein content in slime and decreases of both
      protein and polysaccharide contents in TB-EPS and Slime+LB+TB layers improved
      sludge dewaterability during sludge bioleaching process. Moreover, the low sludge
      pH (2.92) and the increasing distribution of Fe in the solid phase were another
      two factors responsible for the improvement of sludge dewaterability during
      bioleaching. This study suggested that during sludge bioleaching the growth of
      Acidithiobacillus species resulted in the decrease of sludge pH, the increasing
      distribution of Fe in the solid phase, and the decrease of EPS content (mainly
      including protein and/or polysaccharide) in the slime, TB-EPS, and Slime+LB+TB
      layers, all of which are helpful for sludge dewaterability enhancement. 

PMID- 25050972
TI  - Enhancement of vaccine efficacy by expression of a TLR5 ligand in the defined
      live attenuated Francisella tularensis subsp. novicida strain
      U112DeltaiglB::fljB.
AB  - Oral vaccination with the defined live attenuated Francisella novicida vaccine
      strain U112DeltaiglB has been demonstrated to induce protective immunity against
      pulmonary challenge with the highly human virulent Francisella tularensis strain
      SCHU S4. However, this vaccination regimen requires a booster dose in mice and
      Exhibits 50% protective efficacy in the Fischer 344 rat model. To enhance the
      efficacy of this vaccine strain, we engineered U112DeltaiglB to express the
      Salmonella typhimurium FljB flagellin D1 domain, a TLR5 agonist. The
      U112DeltaiglB::fljB strain was highly attenuated for intracellular macrophage
      replication, and although the FljB protein was expressed within the cytosol, it
      exhibited TLR5 activation in a TLR5-expressing HEK cell line. Additionally,
      infection of splenocytes and lymphocytes with U112DeltaiglB::fljB induced
      significantly greater TNF-alpha production than infection with U112DeltaiglB.
      Oral vaccination with U112DeltaiglB::fljB also induced significantly greater
      protection than U112DeltaiglB against pulmonary SCHU S4 challenge in rats. The
      enhanced protection was accompanied by higher IgG2a production and serum-mediated
      reduction of Francisella infectivity. Thus, the U112DeltaiglB::fljB strain may
      serve as a potential vaccine candidate against pneumonic tularemia.

PMID- 25050973
TI  - Comparative efficacy of two next-generation Rift Valley fever vaccines.
AB  - Rift Valley fever virus (RVFV) is a re-emerging zoonotic bunyavirus of the genus
      Phlebovirus. A natural isolate containing a large attenuating deletion in the
      small (S) genome segment previously yielded a highly effective vaccine virus,
      named Clone 13. The deletion in the S segment abrogates expression of the NSs
      protein, which is the major virulence factor of the virus. To develop a vaccine
      of even higher safety, a virus named R566 was created by natural laboratory
      reassortment. The R566 virus combines the S segment of the Clone 13 virus with
      additional attenuating mutations on the other two genome segments M and L,
      derived from the previously created MP-12 vaccine virus. To achieve the same
      objective, a nonspreading RVFV (NSR-Gn) was created by reverse-genetics, which
      not only lacks the NSs gene but also the complete M genome segment. We have now
      compared the vaccine efficacies of these two next-generation vaccines and
      included the Clone 13 vaccine as a control for optimal efficacy. Groups of eight
      lambs were vaccinated once and challenged three weeks later. All mock-vaccinated
      lambs developed high fever and viremia and three lambs did not survive the
      infection. As expected, lambs vaccinated with Clone 13 were protected from
      viremia and clinical signs. Two lambs vaccinated with R566 developed mild fever
      after challenge infection, which was associated with low levels of viral RNA in
      the blood, whereas vaccination with the NSR-Gn vaccine completely prevented
      viremia and clinical signs. 

PMID- 25050974
TI  - HBx elevates oncoprotein AEG-1 expression to promote cell migration by
      downregulating miR-375 and miR-136 in malignant hepatocytes.
AB  - The hepatitis B viral X protein (HBx) has been established to implicate in the
      development of HBV-related hepatocellular carcinoma (HCC) via multiple pathways.
      The oncoprotein astrocyte elevated gene-1 (AEG-1) is overexpressed in various
      tumors, including HCC, and plays critical roles in promoting cell migration and
      invasion. However, the mechanisms for AEG-1 upregulation in tumors are largely
      unknown. In this study, we found that HBx could elevate AEG-1 protein level
      without altering its mRNA level. When blocking AEG-1 expression with siRNA in HBx
      transfected cells, the HBx-induced cell migration was significantly suppressed.
      Further study indicated that miR-375 and miR-136 that targeted AEG-1 were
      downregulated with HBx expression. Overexpressing miR-375 and miR-136 could
      effectively attenuate HBx-mediated AEG-1 elevation and cell migration. These
      results demonstrated that HBx enabled to increase oncoprotein AEG-1 expression to
      promote cell migration via downregulating miR-375 and miR-136. Our findings
      provide a novel insight into AEG-1 upregulation in HCC and shed new light on HBx
      promoting HCC progression. Meanwhile, our results also suggest that miR-375 and
      miR-136 may have the miRNA-based therapeutic potential in HBV-associated HCC. 

PMID- 25050976
TI  - The role of the novel oral anticoagulants in the secondary prevention of acute
      coronary syndromes.
AB  - Acute coronary syndromes continue to be a dominant cause of death worldwide.
      Acute therapies with potent antithrombotic agents have improved in-hospital
      outcomes; however, despite the use of these therapies, recurrent events continue
      to occur long term. Statins, renin-angiotensin inhibitors, beta-blockers, and
      dual antiplatelet therapy all have roles in mitigating long-term risk, but given
      recurrent thrombotic events on contemporary pharmacologic agents, novel therapies
      inhibiting thrombin formation have been explored. The intent of the current
      article is to review recent phase II/III clinical trials of oral anticoagulants
      used for the prevention of acute coronary syndromes. 

PMID- 25050975
TI  - Prevention and treatment in utero of autoimmune-associated congenital heart
      block.
AB  - Transplacental transfer of maternal anti-Ro and/or anti-La autoantibodies can
      result in fetal cardiac disease, including congenital heart block and
      cardiomyopathy, called cardiac neonatal lupus (NL). Thousands of women are faced
      with the risk of cardiac NL in their offspring, which is associated with
      significant morbidity and mortality. There are no known therapies to permanently
      reverse third-degree heart block in NL, although several treatments have shown
      some effectiveness in incomplete heart block and disease beyond the
      atrioventricular node. Fluorinated steroids taken during pregnancy have shown
      benefit in these situations, although adverse effects may be concerning.
      Published data are discordant on the efficacy of fluorinated steroids in the
      prevention of mortality in cardiac NL. beta-agonists have been used to increase
      fetal heart rates in utero. The endurance of beta-agonist effect and its impact
      on mortality are in question, but when used in combination with other therapies,
      they may provide benefit. No controlled experiments regarding the use of
      plasmapheresis in cardiac NL have been performed, despite its theoretical
      benefits. Intravenous immunoglobulin was not shown to prevent cardiac NL at a
      dose of 400 mg/kg, although it has shown effectiveness in the treatment of
      associated cardiomyopathy both in utero and after birth. Retrospective studies
      have shown that hydroxychloroquine may prevent the recurrence of cardiac NL in
      families with a previously affected child, and a prospective open-label trial is
      currently recruiting patients in order to fully evaluate this relationship. 

PMID- 25050977
TI  - Prognostic role of platelet reactivity in patients with acute coronary syndromes.
AB  - Despite dual antiplatelet treatment with aspirin and clopidogrel, patients with
      acute coronary syndromes (ACSs) remain at risk for recurrent cardiovascular
      events. This may be due, at least in part, to an incomplete response to
      clopidogrel, which is more frequent in ACS patients compared to stable patients
      because of massive platelet activation and increased platelet turnover.
      Currently, numerous laboratory-based methods and point-of-care tests are
      available to assess platelet reactivity. Several studies have tried to establish
      a standardized definition of high on-treatment platelet reactivity and to
      evaluate a correlation between this aggregometric phenomenon and clinical
      outcomes. Indeed a strong relationship between high on-treatment platelet
      reactivity and ischemic events was found, especially in high-risk ACS patients
      undergoing percutaneous coronary revascularization. Therefore, evaluation of
      platelet reactivity in this subset of patients may guide physicians to choose the
      best antiplatelet regimen for the individual patient avoiding both ischemic and
      bleeding complications. This was the rationale for tailored antiplatelet therapy
      pursued by utilization of different clopidogrel regimens, more potent P2Y12
      receptor antagonists, or more extensive administration of glycoprotein IIb/IIIa
      inhibitors. To date, data from randomized studies addressing the concept of
      tailored antiplatelet therapy did not show any clinical benefit from a strategy
      based on platelet reactivity monitoring. However, as predominantly elective and
      stable patients were included into the latter studies, these results cannot be
      completely transferred into an ACS setting. This review summarizes current
      evidence about the potential role of platelet reactivity in the therapeutic
      management of patients with ACS. 

PMID- 25050978
TI  - Ultrasonication aided in-situ transesterification of microbial lipids to
      biodiesel.
AB  - In-situ transesterification of microbial lipid to biodiesel has been paid
      substantial attention due to the fact that the lipid extraction and
      transesterification can be conducted in one-stage process. To improve the
      feasibility of in-situ transesterification, ultrasonication was employed to
      reduce methanol requirement and reaction time. The results showed that the use of
      ultrasonication could achieve high conversion of lipid to FAMEs (92.1% w lipid
      conversion/w total lipids) with methanol to lipid molar ratio 60:1 and NaOH
      addition 1% w/w lipid in 20 min, while methanol to lipid molar ratio 360:1, NaOH
      addition 1% w/w lipid, and reaction time 12h was required to obtain similar yield
      in in-situ transesterification without ultrasonication. The compositions of FAMEs
      obtained in case of ultrasonication aided in-situ transesterification were
      similar as that of two-stage extraction followed by transesterification
      processes.

PMID- 25050980
TI  - Phylogenetic and temporal dynamics of human immunodeficiency virus type 1B in
      China: four types of B strains circulate in China.
AB  - To investigate the origin and evolutionary history of the spread of HIV-1 subtype
      B in China, a total of 409 sequences of pol gene sampled from 1994 to 2012 in 29
      provinces across China was subjected to phylogenetic and Bayesian molecular clock
      analyses. The study reveals that subtype B strains in China are genetically
      diverse and can be classified into four distinct subgroups, namely B' (Thai-B),
      BJ-B (Beijing-B), Pan-B (Pandemic-B), and TW-B (Taiwan-B), according to the
      origin of the sequences. The BJ-B and TW-B are reported for the first time.
      Phylogeographic analysis reveals that B' exhibits a nationwide, transprovincial
      distribution, and is found in 21 provinces in China in this study, whereas the
      Pan-B, BJ-B, and TW-B lineages are restricted to particular regions. From the
      same common ancestor of B', there arise two subclusters in which sequences from
      Yunnan occupy the basal position. The times of the most recent common ancestors
      (tMRCAs) of B' and BJ-B are estimated to be 1983.6 (1975.9-1990.3) and 1995.3
      (1989.6-2000.3), respectively. The skyline plot profile reveals an exponential
      decrease in median number of effective infections of subtype B in China from 1994
      to 2009. The existence of four types of B clades also indicates distinct
      transmission networks of subtype B, originating from different introduction
      events at different time points. The data presented here offer a new perspective
      on the epidemic of HIV-1 subtype B in China.

PMID- 25050979
TI  - Efficacy of selective PDE4D negative allosteric modulators in the object
      retrieval task in female cynomolgus monkeys (Macaca fascicularis).
AB  - Cyclic adenosine monophosphate (cAMP) signalling plays an important role in
      synaptic plasticity and information processing in the hippocampal and basal
      ganglia systems. The augmentation of cAMP signalling through the selective
      inhibition of phosphodiesterases represents a viable strategy to treat disorders
      associated with dysfunction of these circuits. The phosphodiesterase (PDE) type 4
      inhibitor rolipram has shown significant pro-cognitive effects in neurological
      disease models, both in rodents and primates. However, competitive non-isoform
      selective PDE4 inhibitors have a low therapeutic index which has stalled their
      clinical development. Here, we demonstrate the pro-cognitive effects of selective
      negative allosteric modulators (NAMs) of PDE4D, D159687 and D159797 in female
      Cynomolgous macaques, in the object retrieval detour task. The efficacy displayed
      by these NAMs in a primate cognitive task which engages the corticostriatal
      circuitry, together with their suitable pharmacokinetic properties and safety
      profiles, suggests that clinical development of these allosteric modulators
      should be considered for the treatment of a variety of brain disorders associated
      with cognitive decline. 

PMID- 25050981
TI  - Subangstrom accuracy in pHLA-I modeling by Rosetta FlexPepDock refinement
      protocol.
AB  - Flexible peptides binding to human leukocyte antigen (HLA) play a key role in
      mediating human immune responses and are also involved in idiosyncratic adverse
      drug reactions according to recent research. However, the structural
      determinations of pHLA complexes remain challenging under the present conditions.
      In this paper, the performance of a new peptide docking method, namely
      FlexPepDock, was systematically investigated by a benchmark of 30 crystallized
      structures of peptide-HLA class I complexes. The docking results showed that the
      near-native pHLA-I models with peptide bb-RMSD less than 2 A were ranked in the
      top 1 model for 100% (70/70) docking cases, and the subangstrom models with
      peptide bb-RMSD less than 1 A were ranked in the top 5 lowest-energy models for
      65.7% (46/70) docking cases. Furthermore, 10 out of 70 docking cases ranked the
      subangstrom all-atom models in the top 5 lowest-energy models. The results showed
      that the FlexPepDock can generate high-quality models of pHLA-I complexes and can
      be widely applied to pHLA-I modeling and mechanism research of peptide-mediated
      immune responses. 

PMID- 25050982
TI  - Involvement of connexin43 in the acute hyperosmotic stimulus-induced synthesis
      and release of vasopressin in the supraoptic nucleus of rats.
AB  - There is evidence that astroglial connexin43 (Cx43) in the supraoptic nucleus
      (SON) is required for the hyperosmolarity-induced increase in Fos protein
      expression in magnocellular neurosecretory cells (MNCs). In the present study,
      the role of astroglial Cx43 in the synthesis and release of vasopressin (VP) by
      MNCs in the SON subjected to hyperosmotic stimulus was examined. The results
      revealed that the VP levels in the SON and plasma were increased following acute
      hyperosmotic stimulus. Treatment of MNCs with Cx43-specific antisense
      oligodeoxynucleotides (ASODN), which temporarily reduced Cx43 protein production,
      limited the VP synthesis and release induced by a hyperosmotic stimulus.
      Similarly, the addition of gap junction and Cx43 hemichannel blockers also
      attenuated the VP synthesis and release induced by an acute hyperosmotic
      stimulus. A high extracellular [Ca2+]([Ca2+]o) has been demonstrated to reduce
      the gap junction activity or opening probability of Cx54 hemichannels. Notably,
      it was identified that high [Ca2+]o attenuated the VP synthesis and release
      induced by acute hyperosmotic stimulus, while low [Ca2+]o had a weak or no
      effect. These results suggested that Cx43 participates in the VP synthesis and
      release induced by hyperosmotic stimulation in the SON.

PMID- 25050984
TI  - High density LD-based structural variations analysis in cattle genome.
AB  - Genomic structural variations represent an important source of genetic variation
      in mammal genomes, thus, they are commonly related to phenotypic expressions. In
      this work, ~ 770,000 single nucleotide polymorphism genotypes from 506 animals
      from 19 cattle breeds were analyzed. A simple LD-based structural variation was
      defined, and a genome-wide analysis was performed. After applying some quality
      control filters, for each breed and each chromosome we calculated the linkage
      disequilibrium (r2) of short range (<= 100 Kb). We sorted SNP pairs by distance
      and obtained a set of LD means (called the expected means) using bins of 5 Kb. We
      identified 15,246 segments of at least 1 Kb, among the 19 breeds, consisting of
      sets of at least 3 adjacent SNPs so that, for each SNP, r2 within its neighbors
      in a 100 Kb range, to the right side of that SNP, were all bigger than, or all
      smaller than, the corresponding expected mean, and their P-value were significant
      after a Benjamini-Hochberg multiple testing correction. In addition, to account
      just for homogeneously distributed regions we considered only SNPs having at
      least 15 SNP neighbors within 100 Kb. We defined such segments as structural
      variations. By grouping all variations across all animals in the sample we
      defined 9,146 regions, involving a total of 53,137 SNPs; representing the 6.40%
      (160.98 Mb) from the bovine genome. The identified structural variations covered
      3,109 genes. Clustering analysis showed the relatedness of breeds given the
      geographic region in which they are evolving. In summary, we present an analysis
      of structural variations based on the deviation of the expected short range LD
      between SNPs in the bovine genome. With an intuitive and simple definition based
      only on SNPs data it was possible to discern closeness of breeds due to grouping
      by geographic region in which they are evolving.

PMID- 25050985
TI  - Understanding the needs of hand control users, driver rehabilitation specialists,
      and dealers/installers.
AB  - Understanding unique perspectives from key stakeholder groups involved in the
      hand control (HC) industry, including driver rehabilitation specialists (DRSs)
      who train users how to use their HCs, dealers/installers, and users, may become
      increasingly important in the United States due to increases in elderly,
      diabetic, and wounded warrior amputee driving populations. In this exploratory
      study, phone interviews were conducted with 20 DRSs, 20 dealers/installers, and
      20 users regarding their perspectives about HC training, maintenance and
      operation, and design improvements. Results revealed common views and differences
      in perspectives about whether HC users should receive training and for how long,
      when and how often users should receive maintenance on their HCs, and what DRSs,
      dealers/installers, and users would like to see in the future.

PMID- 25050986
TI  - Comparison between lactate minimum and critical speed throughout childhood and
      adolescence in swimmers.
AB  - This study aimed to examine the influence of age and degree of maturity on the
      comparison and relationship between lactate minimum intensity (LM) and critical
      speed (CS) throughout childhood and adolescence in swimmers. Forty-six male
      swimmers aged between 10 and 18 years were divided into three age groups
      according to pubertal stages and training status. Maximal efforts of 100 and 400
      m and the LM protocol with 200 m performances were executed. CS was determined
      with a 3-distances combination (100, 200, and 400 m). One-way and mixed analysis
      of variance for repeated measures, Bland-Altman, Pearson correlation, percentage
      difference, and effect size were used to compare and examine the relationship
      between variables in each age group. The results revealed that LM and CS had
      differences in comparison with one another throughout childhood and adolescence
      in swimmers, because CS clearly underestimated LM in the 10 to 12.6-year age
      group, while overestimating it in the 15.4 to 18-year age group of swimmers.
      Thus, coaches and swimmers must be aware of the age-dependency of CS for indices
      of aerobic endurance measurements in the initial ages of systematized swimming
      training. 

PMID- 25050987
TI  - Syntheses, crystal structures, and optical properties of five metal complexes
      constructed from a V-shaped thiophene-containing ligand and different
      dicarboxylate ligands.
AB  - Five new metal complexes, {[Ni(DIDP)(m-bdc)(H2O)].5H2O}n (1),
      {[Zn(DIDP)(hfipbb)].2DMA}n (2), {[Zn(DIDP)(4,4'-sdb)].H2O}n (3), {[Co(DIDP)(p
      bdc)]}n (4), and {[Co2(DIDP)(hfipbb)2].H2O}n (5), have been synthesized by
      reactions of the corresponding metal ions with a V-shaped ligand 2,8-di(1H
      imidazol-1-yl)dibenzothiophene (DIDP) and different aromatic dicarboxylic acids,
      namely isophthalic acid (m-H2bdc), terephthalic acid (p-H2bdc), 4,4'
      (hexafluoroisopropylidene)bis(benzoic acid) (H2hfipbb), and 4,4'
      sulfonyldicarboxylic acid (4,4'-H2sdb), respectively. The structures of the
      complexes were determined by X-ray single-crystal diffraction. Complex 1 is a 1D
      chain structure containing a one-dimensional channel along the a direction and is
      further extended via O-H...S hydrogen bonds and C-H...pi stacking interactions
      into a 3D framework. Complex 2 exhibits a quasi 2D + 2D -> 2D with parallel
      polycatenation of 2D (4, 4) nets. Complex 3 displays an unusual 2D + 2D -> 3D
      parallel polycatenated framework based on a 2D 6(3)-hcb network. Complex 4 shows
      a 2D 4-connected {4(4).6(2)}-sql network containing a one-dimensional channel
      along the b direction. The adjacent 2D networks are further extended via C-H...O
      hydrogen bonds into a 3D supramolecular framework. Complex 5 features a 2-fold
      interpenetrating 3D framework with a 6-connected {4(12).6(3)} pcu topology.
      Furthermore, the thermal stability for 1-5 and luminescence properties of 2 and 3
      have been studied. Moreover, the solid-state UV-visible spectroscopy experiments
      show that complexes 1-5 are all optical semiconductors with band gaps of 3.06,
      3.18, 3.23, 2.98, and 3.17 eV, respectively.

PMID- 25050988
TI  - Regioselective alkylation of a methylene group via meta-bridging of
      calix[4]arenes.
AB  - The meta-iodo derivative, fixed in the cone conformation, enables the gram-scale
      preparation of a meta-bridged calix[4]arene. This intermediate, possessing a
      fluorene moiety within the macrocyclic skeleton, can be regioselectively
      alkylated on the corresponding methylene bridge to form a unique substitution
      pattern in classical calixarene chemistry. 

PMID- 25050989
TI  - Differential effects on allele selective silencing of mutant huntingtin by two
      stereoisomers of alpha,beta-constrained nucleic acid.
AB  - We describe the effects of introducing two epimers of neutral backbone alpha,beta
      constrained nucleic acid (CNA) on the activity and allele selectivity profile of
      RNase H active antisense oligonucleotides (ASOs) targeting a single nucleotide
      polymorphism (SNP) for the treatment of Huntington's disease (HD). ASOs modified
      with both isomers of alpha,beta-CNA in the gap region showed good activity versus
      the mutant allele, but one isomer showed improved selectivity versus the wild
      type allele. Analysis of the human RNase H cleavage patterns of alpha,beta-CNA
      modified ASOs versus matched and mismatched RNA revealed that both isomers
      support RNase H cleavage on the RNA strand across from the site of incorporation
      in the ASO--an unusual observation for a neutral linkage oligonucleotide
      modification. Interestingly, ASOs modified with (R)- and (S)-5'-hydroxyethyl DNA
      (RHE and SHE respectively) formed by partial hydrolysis of the dioxaphosphorinane
      ring system in alpha,beta-CNA also showed good activity versus the mutant allele
      but an improved selectivity profile was observed for the RHE modified ASO. Our
      observations further support the profiling of neutral and 5'-modified nucleic
      acid analogs as tools for gene silencing applications.

PMID- 25050990
TI  - Dietary sodium intake and incidence of diabetes complications in Japanese
      patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study
      (JDCS).
AB  - CONTEXT: Many guidelines recommend that patients with type 2 diabetes should
      reduce their dietary sodium intake. However, the relationship between dietary
      sodium intake and incidence of diabetic complications in patients with type 2
      diabetes has not been explored. OBJECTIVE: Our objective was to investigate the
      relationship between dietary sodium intake and incidence of diabetes
      complications. PARTICIPANTS: The study was of a nationwide cohort of patients
      with type 2 diabetes aged 40 to 70 years with hemoglobin A1c (HbA1c) >=6.5%. MAIN
      OUTCOME MEASURES: After excluding nonresponders to a dietary survey, 1588
      patients were analyzed. Baseline dietary intake was assessed by the Food
      Frequency Questionnaire based on food groups. Primary outcomes were times to
      cardiovascular disease (CVD), overt nephropathy, diabetic retinopathy, and all
      cause mortality. RESULTS: Mean daily dietary sodium intake in quartiles ranged
      from 2.8 to 5.9 g. After adjustment for confounders, hazard ratios for CVD in
      patients in the second, third, and fourth quartiles of sodium intake compared
      with the first quartile were 1.70 (95% confidence interval, 0.98-2.94), 1.47
      (0.82-2.62), and 2.07 (1.21-3.90), respectively (trend P < .01). In addition,
      among patients who had HbA1c >=9.0%, the hazard ratio for CVD in patients in the
      top vs bottom quartile of sodium intake was dramatically elevated compared with
      patients with HbA1c <9.0% (1.16 [0.56-2.39] and 9.91 [2.66-36.87], interaction P
      < .01). Overt nephropathy, diabetic retinopathy, and all-cause mortality were not
      significantly associated with sodium intake. CONCLUSIONS: Findings suggested that
      high dietary sodium intake is associated with elevated incidence of CVD in
      patients with type 2 diabetes and that there is a synergistic effect between
      HbA1c values and dietary sodium intake for the development of CVD.

PMID- 25050991
TI  - Serum vitamin D levels in relation to schizophrenia: a systematic review and meta
      analysis of observational studies.
AB  - INTRODUCTION: Although several observational studies have investigated the
      association between vitamin D status and schizophrenia, we are aware of no
      comprehensive meta-analysis in this regard. OBJECTIVE: We aimed to conduct a
      systematic review and a meta-analysis of observational studies to summarize the
      available data on the association between serum vitamin D levels and
      schizophrenia. METHODS: A systematic research on all published articles until
      October 2013 was conducted in PubMed, ISI (Web of science), SCOPUS, and Google
      Scholar. All observational studies that had measured serum vitamin D levels in
      schizophrenic patients were included in the systematic review. After considering
      exclusion criteria, we had 19 studies for the systematic review that were
      included in three separate meta-analyses: 1) a meta-analysis on mean levels of 25
      hydroxyvitamin D [25(OH)D] (n = 13); 2) a meta-analysis on the prevalence of
      vitamin D deficiency (n = 8); 3) a meta-analysis on odds ratios (n = 8). RESULTS:
      Findings from a meta-analysis on means revealed that the overall mean difference
      in serum 25(OH)D levels between schizophrenic patients and control participants
      was -5.91 ng/mL [95% confidence interval (CI) -10.68, -1.14]. Subgroup analyses
      based on study design, the patient's hospitalization status, study quality, and
      study location did not explain between-study heterogeneity; however, type of
      biomarker assessed [25-hydroxyvitamin D3 vs 25-hydroxyvitamin D (D2 & D3)] could
      account for some degree of heterogeneity. RESULTS from the meta-analysis on the
      prevalence of vitamin D deficiency indicated that the overall prevalence of
      vitamin D deficiency in schizophrenic patients was 65.3% (95% CI 46.4%-84.2%).
      Findings from the meta-analysis on odds ratios indicated that vitamin D-deficient
      persons were 2.16 times (95% CI 1.32, 3.56) more likely to have schizophrenia
      than those with vitamin D sufficiency. No evidence of heterogeneity was detected.
      CONCLUSION: We found a strong association between vitamin D deficiency and
      schizophrenia. However, randomized clinical trials are required to confirm our
      findings.

PMID- 25050992
TI  - The association between family history of mental disorders and general cognitive
      ability.
AB  - There is an emerging literature linking cognitive ability with a wide range of
      psychiatric disorders. These findings have led to the hypothesis that diminished
      'cognitive reserve' is a causal risk factor for psychiatric disorders. However,
      it is also feasible that a family history of mental disorders may confound this
      relationship, by contributing to both a slight impairment in cognitive ability,
      and an increased risk of psychiatric disorder. On the basis of a large,
      population-based sample of young adult male conscripts (n=160 608), we examined
      whether the presence of a family history of a range of mental disorders was
      associated with cognitive ability, as tested by the Borge Priens Prove. In those
      with no individual-level history of mental disorder, a family-level history of a
      mental disorder was associated with a slight reduction in cognitive ability. In
      general, this pattern was found regardless of the nature of the psychiatric
      disorder in the family. Our study suggests that shared familial factors may
      underpin both cognitive ability and the risk of a wide range of psychiatric
      disorders. Convergent evidence from epidemiology and genetics suggests that
      shared genetic factors underpin an unexpectedly diverse range of psychiatric
      disorders. On the basis of the findings of the current study, we speculate that
      these same shared genetic factors also contribute to general cognitive ability. 

PMID- 25050994
TI  - Correlations of MTHFR 677C>T polymorphism with cardiovascular disease in patients
      with end-stage renal disease: a meta-analysis.
AB  - OBJECTIVE: This meta-analysis was conducted to evaluate the correlations of a
      common polymorphism (677C>T) in the methylenetetrahydrofolate reductase (MTHFR)
      gene with risk of cardiovascular disease (CVD) in patients with end-stage renal
      disease (ESRD). METHOD: The following electronic databases were searched without
      language restrictions: Web of Science (1945~2013), the Cochrane Library Database
      (Issue 12, 2013), MEDLINE (1966~2013), EMBASE (1980~2013), CINAHL (1982~2013) and
      the Chinese Biomedical Database (CBM) (1982~2013). Meta-analysis was performed
      using STATA statistical software. Odds ratios (ORs) with their 95% confidence
      intervals (95%CIs) were calculated. RESULTS: Eight cohort studies met all
      inclusion criteria and were included in this meta-analysis. A total of 2,292 ESRD
      patients with CVD were involved in this meta-analysis. Our meta-analysis results
      revealed that the MTHFR 677C>T polymorphism might increase the risk of CVD in
      ESRD patients (TT vs. CC: OR = 2.75, 95%CI = 1.35~5.59, P = 0.005; CT+TT vs. CC:
      OR = 1.39, 95%CI = 1.09~1.78, P = 0.008; TT vs. CC+CT: OR = 2.52, 95%CI =
      1.25~5.09, P = 0.010; respectively). Further subgroup analysis by ethnicity
      suggested that the MTHFR 677C>T polymorphism was associated with an elevated risk
      for CVD in ESRD patients among Asians (TT vs. CC: OR = 3.38, 95%CI = 1.11~10.28,
      P = 0.032; CT+TT vs. CC: OR = 1.44, 95%CI = 1.05~1.97, P = 0.022; TT vs. CC+CT:
      OR = 3.15, 95%CI = 1.02~9.72, P = 0.046; respectively), but not among Africans or
      Caucasians (all P>0.05). CONCLUSION: Our findings indicate that the MTHFR 677C>T
      polymorphism may be associated with an elevated risk for CVD in ESRD patients,
      especially among Asians.

PMID- 25050993
TI  - Association of trauma exposure with proinflammatory activity: a transdiagnostic
      meta-analysis.
AB  - Exposure to psychological trauma (for example, childhood/early life adversity,
      exposure to violence or assault, combat exposure, accidents or natural disasters)
      is known to increase one's risk of developing certain chronic medical conditions.
      Clinical and population studies provide evidence of systemic inflammatory
      activity in trauma survivors with various psychiatric and nonpsychiatric
      conditions. This transdiagnostic meta-analysis quantitatively integrates the
      literature on the relationship of inflammatory biomarkers to trauma exposure and
      related symptomatology. We conducted random effects meta-analyses relating trauma
      exposure to log-transformed inflammatory biomarker concentrations, using meta
      regression models to test the effects of study quality and psychiatric
      symptomatology on the inflammatory outcomes. Across k=36 independent samples and
      n=14,991 participants, trauma exposure was positively associated with C-reactive
      protein (CRP), interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)
      alpha (mean rs =0.2455, 0.3067, 0.2890, and 0.2998, respectively). No significant
      relationships were noted with fibrinogen, IL-2, IL-4, IL-8, or IL-10. In meta
      regression models, the presence of psychiatric symptoms was a significant
      predictor of increased effect sizes for IL-1beta and IL-6 (beta=1.0175 and
      0.3568, respectively), whereas study quality assessment scores were associated
      with increased effect sizes for IL-6 (beta=0.3812). Positive correlations between
      inflammation and trauma exposure across a range of sample types and diagnoses
      were found. Although reviewed studies spanned an array of populations, research
      on any one specific psychiatric diagnosis was generally limited to one or two
      studies. The results suggest that chronic inflammation likely represents one
      potential mechanism underlying risk of health problems in trauma survivors.

PMID- 25050995
TI  - Uncertainty and variability in the exposure reconstruction of chemical incidents-
      the case of acrylonitrile.
AB  - The application of human physiologically based pharmacokinetic (PBPK) modeling
      combined with measured biomonitoring data, has a great potential to backtrack
      external exposure to chemicals during chemical incidents. So far, an important
      shortcoming of 'reversed dosimetry' is that uncertainty and variability in the
      model predictions are often neglected. The aim of this paper is to characterize
      the variation in predicted environmental air concentrations by means of reversed
      dosimetry as a result of uncertainty in chemical-specific input data and
      variability in physiological parameters. Human biomonitoring data (N-2
      cyanoethylvaline in blood) from a chemical incident with acrylonitrile (ACN)
      combined with the BioNormtox PBPK model are used as a case to reconstruct the air
      concentration and uncertainty thereof at the time of the incident. The influence
      of uncertainty in chemical-specific properties and exposure duration, and
      interindividual variability in physiological parameters on the reconstructed air
      exposure concentrations were quantified via nested Monte Carlo simulation. The
      range in the reconstructed air concentrations of ACN during the incident was
      within a factor of 3. Uncertainty in the exact exposure duration directly after
      the chemical accident was found to have a dominant influence on the model
      outcomes. It was also shown that uncertainty can be further reduced by collecting
      human biomonitoring data as soon as possible after the incident. Finally, the
      collection of specific information about individual physiological parameters from
      the victims, such as body weight, may further reduce the variation by 5 to 20% in
      our case study. Future research should include the comparison of reversed
      dosimetry model outcomes with measured air and biological concentrations to
      further increase the confidence in the model approach and its implementation in
      practice. 

PMID- 25050996
TI  - Oncogenic role of long noncoding RNA AF118081 in anti-benzo[a]pyrene-trans-7,8
      dihydrodiol-9,10-epoxide-transformed 16HBE cells.
AB  - Lung cancer is the leading cause of cancer deaths and remains an important public
      health problem worldwide. Long noncoding RNAs (lncRNAs) are newly identified
      regulators of tumorigenesis and tumor progression. However, the role of lncRNAs
      in lung cancer induced by environmental carcinogens remains largely unknown. In
      this study, an lncRNA microarray was used to compare the expression profiles of
      malignantly transformed 16HBE cells (16HBE-T) induced with anti-benzo[a]pyrene
      trans-7,8-diol-9,10-epoxide (anti-BPDE) and normal 16HBE cells (16HBE-N). Using
      quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR),
      lncRNA AF118081 was identified as the most significantly overexpressed lncRNA in
      16HBE-T cells, lung cancer cells, and patient samples. Cell proliferation, colony
      formation, apoptosis, migration, and invasion were assayed in 16HBE-T cells
      following the knockdown of lncRNA AF118081 with small interfering RNA. AF118081
      knockdown inhibited cell growth and tumor invasion. An in vivo (nude mouse) model
      was then used to assay tumor growth, and the downregulation of AF118081 clearly
      suppressed tumor growth, consistent with the results of the in vitro assays.
      Together, these findings identify a new oncogenic lncRNA, lncRNA AF118081, in
      malignantly transformed 16HBE cells. This enhances our understanding of lncRNAs
      as important regulatory elements in chemical carcinogenesis and potential targets
      of lung cancer therapies. 

PMID- 25050997
TI  - siRNA-mediated silencing of Wnt5a regulates inflammatory responses in
      atherosclerosis through the MAPK/NF-kappaB pathways.
AB  - Previous studies have demonstrated that the aberrant expression of Wnt5a occurs
      in atherosclerotic lesions. However, the precise role of Wnt5a in the
      pathogenesis of atherosclerosis remains largely unknown. The present study was
      undertaken to determine whether the RNA interference of Wnt5a in vivo by
      adenovirus (Ad)-mediated small interfering RNA (siRNA) transfection is capable of
      inhibiting the progression of atherosclerosis. Recombinant adenovirus carrying
      siRNA targeting Wnt5a (Ad-Wnt5a siRNA) was designed. Male apolipoprotein E
      deficient (ApoE(-/-)) mice were fed a high-fat diet to induce the pathogenesis of
      atherosclerosis. Mice were randomly divided into 3 groups (n=15 in each group):
      the mock group, which received treatment with phosphate-buffered saline (PBS);
      the Ad-NC group, which received treatment with Ad-non-specific siRNA; and the Ad
      Wnt5a siRNA group, which received treatment with Ad-Wnt5a siRNA. Treatment with
      Ad-Wnt5a siRNA markedly inhibited the mRNA and protein expression of Wnt5a in the
      aortic tissues. The knockdown of Wnt5a had no significant effect on blood lipid
      levels, but it suppressed atherosclerotic development and increased plaque
      stability, which was determined by hematoxylin and eosin staining, picrosirius
      red staining and Oil Red O staining. Furthermore, the mRNA and protein expression
      of inflammatory cytokines, including monocyte chemotactic protein-1 (MCP-1),
      cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP)-2 and MMP-9 was
      significantly downregulated in the Ad-Wnt5a siRNA group. In addition, the
      knockdown of Wnt5a inhibited the nuclear factor-kappaB (NF-kappaB) and mitogen
      activated protein kinase (MAPK) signaling pathways. These results demonstrate
      that Ad-mediated Wnt5a silencing in vivo attenuates the development of
      atherosclerotic disease by reducing inflammatory mediators involved in the
      MAPK/NF-kappaB pathways.

PMID- 25050998
TI  - Neoadjuvant sunitinib effectiveness in T4 renal clear cell carcinoma: a case
      report.
AB  - INTRODUCTION:  INTRODUCTION: Sunitinib therapy showed an improvement in survival
      of patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: 
      MATERIALS AND METHODS: A 51-year-old man, with Eastern Cooperative Oncology Group
      Score (ECOG) of 0, presented at our Institute in March 2012 for macrohematuria
      and urinary retention. A computed tomography (CT) scan of the abdomen showed a
      right renal lesion. The lesion had a diameter of 15 cm and was developing towards
      the liver, in the absence of cleavage planes between the liver and kidney. A 12
      mm finding, suspected as secondary lesion, was detected at the level of the VII
      hepatic segment. Neoadjuvant chemotherapy with Sunitinib was proposed. RESULTS: 
      RESULTS: The patient underwent a ultrasound-guided biopsy, which confirmed the
      presence of Clear Cell Carcinoma. The patient began chemotherapy treatment in May
      2012 according to the scheme SUNITINIB 50 mg daily for 4 weeks every 6 weeks.
      After four courses of treatment, according to RECIST criteria for solid tumors,
      40% (9 cm vs 15 cm) regression of the primary tumor and 33% (8 mm vs 12 mm)
      regression of the secondary lesion were observed at a CT scan of the abdomen. In
      February 2013, Laparoscopic Adrenal-Sparing Radical Nephrectomy was performed. At
      a follow-up of 3 months, performed with a thorax and abdomen CT scans, there was
      a complete remission of hepatic secondary lesion and no areas of secondary
      localization of disease. CONCLUSION:  CONCLUSION: This case report showed the
      effectiveness of neoadjuvant chemotherapy with Sunitinib. The use of this
      chemotherapy agent can change the approach to the management of cRCC.

PMID- 25050999
TI  - [Imaging of medullary sponge kidney: notes for urologists].
AB  - The medullary sponge kidney is a malformation characterized by Bellini ducts'
      ectasias and often by nephrocalcinosis. Scientific literature demonstrates and
      emphasizes how the Rx-urography plays a primary role to achieve diagnostic
      certainty in cases of suspected MSK. Pathognomonic urographic aspects in cases of
      medullary sponge kidney are defined as "bouquet of flowers", "bunch of grapes" or
      "brush". None of the other methods of imaging available today has the same
      diagnostic accuracy. 

PMID- 25051000
TI  - Acute static vibration-induced stretching enhanced muscle viscoelasticity but did
      not affect maximal voluntary contractions in footballers.
AB  - The aim of this study was to compare the effects of acute vibration-enhanced
      static stretching and/or static stretching alone on the strength and flexibility
      of the hamstrings and quadriceps muscles. Twenty-one male footballers
      participated in this study (21.9 +/- 1.8 years; 75.54 +/- 7.3 kg; 178.7 +/- 6.5
      cm). The experiment started with 5 minutes standardized warm-up followed by (a)
      baseline flexibility pretest (Split Test); (b) maximal voluntary flexion and
      extension (isokinetic strength) of the knee; (c) Treatment or Sham involving 45
      second stretch with or without vibration for the hamstring and quadriceps muscle
      groups with 10-second rest between; and (d) posttest repeating the measures of
      the pretest. Each player randomly performed both trials on separate occasions.
      The vibration device operated at 35 Hz with 2 mm amplitude. Stretching with
      vibration statistically increased hamstring flexibility by 7.8% (p <= 0.05) when
      compared with stretching without vibration. No statistical differences for
      hamstring or quadriceps strength were noted between treatment conditions. There
      was no statistical correlation between flexibility and strength measurements. In
      conclusion, flexibility increased with vibration-enhanced static stretching;
      however, no change was evident in the maximal voluntary contractions of the knee
      flexors and extensors.

PMID- 25051001
TI  - Similar increases in strength after short-term resistance training due to
      different neuromuscular adaptations in young and older men.
AB  - This study investigated whether differences in neuromuscular performance and
      muscle hypertrophy occur between young and older men. Twenty-three young (29 +/-
      9 years) and 26 older men (64 +/- 8 years) completed 10 weeks of high-volume,
      medium load "hypertrophic" resistance training with low frequency (twice per
      week) with 10 young (34 +/- 11 years) and 11 older men (65 +/- 3 years) acting as
      nontraining control subjects. Training consisted of 2-5 sets of 8-14 repetitions
      (1- to 2-minute rest). Lower-limb dynamic (leg press) and isometric maximum leg
      extension force, as well as lower-limb lean mass and vastus lateralis cross
      sectional area were assessed before and after the training period. Training led
      to significant increases in 1 repetition maximum (1RM) leg press performance in
      both training groups (young: 13 +/- 7%, p < 0.001; older: 14 +/- 9%, p < 0.001).
      Performance improvements were accompanied by increased muscle activation,
      assessed by voluntary activation level (29 +/- 51%, p <= 0.05) and
      electromyography amplitude (35 +/- 51%, p < 0.01) in older men only. Conversely,
      only young men showed significantly increased lower-limb lean mass (2.4 +/- 2.5%,
      p < 0.01). Furthermore, increases in 1RM performance and lower-limb lean mass
      were significantly related in young men only (r = 0.524, p = 0.01, n = 23). In
      conclusion, although high-volume, medium load "hypertrophic" resistance training
      may induce similar improvements in strength between young and older men, it
      appears that different mechanisms underpin these improvements.

PMID- 25051002
TI  - Effects of Three Recovery Protocols on Range of Motion, Heart Rate, Rating of
      Perceived Exertion, and Blood Lactate in Baseball Pitchers During a Simulated
      Game.
AB  - Baseball pitching has been described as an anaerobic activity from a
      bioenergetics standpoint with short bouts of recovery. Depending on the physical
      conditioning and muscle fiber composition of the pitcher as well as the number of
      pitches thrown per inning and per game, there is the possibility of pitchers
      fatiguing during a game, which could lead to a decrease in pitching performance.
      Therefore, the purpose of this study was to evaluate the effects of 3 recovery
      protocols: passive recovery, active recovery (AR), and electrical muscle
      stimulation (EMS) on range of motion (ROM), heart rate (HR), rating of perceived
      exertion (RPE), and blood lactate concentration in baseball pitchers during a
      simulated game. Twenty-one Division I intercollegiate baseball pitchers (age =
      20.4 +/- 1.4 years; height = 185.9 +/- 8.4 cm; weight = 86.5 +/- 8.9 kg; percent
      body fat = 11.2 +/- 2.6) volunteered to pitch 3 simulated 5-inning games, with a
      maximum of 70 fastballs thrown per game while wearing an HR monitor. Range of
      motion was measured pre, post, and 24 hours postpitching for shoulder internal
      and external rotation at 90 degrees  and elbow flexion and extension. Heart rate
      was recorded after each pitch and after every 30 seconds of the 6-minute recovery
      period. Rating of perceived exertion was recorded after the last pitch of each
      inning and after completing each 6-minute recovery period. Immediately after
      throwing the last pitch of each inning, postpitching blood lactate concentration
      (PPLa-) was measured. At the end of the 6-minute recovery period, before the next
      inning started, postrecovery blood lactate concentration (PRLa-) was measured.
      Pitchers were instructed to throw each pitch at or above 95% of their best
      pitched fastball. This was enforced to ensure that each pitcher was throwing
      close to maximal effort for all 3 simulated games. All data presented represent
      group mean values. Results revealed that the method of recovery protocol did not
      significantly influence ROM (p > 0.05); however, it did significantly influence
      blood lactate concentration (p < 0.001), HR (p < 0.001), and RPE (p = 0.01).
      Blood lactate concentration significantly decreased from postpitching to
      postrecovery in the EMS recovery condition (p < 0.001), but did not change for
      either the active (p = 0.04) or the passive (p = 0.684) recovery conditions.
      Rating of perceived exertion decreased from the postpitching to postrecovery in
      both the passive and EMS recovery methods (p < 0.001), but did not decrease for
      AR (p = 0.067). Heart rate decreased for all conditions from postpitching to
      postrecovery (p < 0.001). The use of EMS was the most effective method at
      reducing blood lactate concentration after 6 minutes of recovery during a
      simulated game (controlled setting). Although EMS significantly reduced blood
      lactate concentrations after recovery, blood lactate concentrations after
      pitching in the simulated games were never high enough to cause skeletal muscle
      fatigue and decrease pitching velocity. If a pitcher were to throw more than 14
      pitches per inning, throw more total pitches than normal per game, and have blood
      lactate concentrations increase higher than in the simulated games in this study,
      the EMS recovery protocol may be beneficial to pitching performance by aiding
      recovery. This could potentially reduce some injuries associated with skeletal
      muscle fatigue during pitching, may allow a pitcher throw more pitches per game,
      and may reduce the number of days between pitching appearances.

PMID- 25051004
TI  - Short bouts of high-intensity resistance-style training produce similar
      reductions in fasting blood glucose of diabetic offspring and controls.
AB  - Family history of diabetes (FH) is associated with impaired cardiometabolic
      function. Aerobic exercise improves insulin sensitivity, though resistance
      training studies on fasting glucose (FG) in FH are lacking. This study examined
      the effects of 7 weeks of high-intensity-resistance-focused training (HIRFT),
      including circuit, core, and plyometric resistance training on FG in FH and
      matched controls (CON). We hypothesized that HIRFT would reduce FG levels, with
      greater reductions in CON. Thirty-eight healthy men and women (23.5 +/- 2 years;
      171 +/- 7.4 cm; 71 +/- 14 kg) participated in 7 weeks of HIRFT including full
      body, plyometric, and core resistance training on alternate days. Fasting glucose
      was analyzed before and after the 7-week training before and after workouts. One
      repetition maximum was calculated for bench press, squat, and deadlift before and
      after training. Body mass index and resting HR remained unchanged. Fasting
      glucose declined similarly between groups with training (-0.23 +/- 0.08 vs. -0.20
      +/- 0.07 mmol.L, p < 0.01 for FH and CON, respectively), whereas strength
      increased (kg) (bench: 8.0 +/- 1.8, squat: 19.4 +/- 4.6, deadlift: 16.4 +/- 3.6,
      overall mean percent increase: 38.9 +/- 9.2, p < 0.001). Ten-minute postexercise
      glucose decreased (-0.65 mmol.L, p = 0.05) with training, with no differences
      between groups. Changes in FG and strength increase were inversely correlated (r
      = -0.519, p = 0.05). Strength increased equally between groups. Data indicate
      that HIRFT reduces FG concentrations similarly in FH and CON, making it effective
      for improving FG in FH.

PMID- 25051005
TI  - Intensive resistance exercise and circadian salivary testosterone concentrations
      among young male recreational lifters.
AB  - Strength and morphological adaptations to resistance exercise are mediated in
      part by anabolic hormones such as testosterone, yet the time course of
      variability in circadian hormone concentrations is not well characterized. This
      study, investigated how the circadian rhythm of salivary testosterone is altered
      by resistance exercise in young men. Twenty healthy young male recreational
      lifters (age, 18.0 +/- 1.3 years) with 2 years of experience in weightlifting
      were recruited. A randomized controlled trial was conducted, and subjects were
      randomly assigned to either the resistance exercise group (n = 10), who completed
      a series of resistance exercise (3 times a week, in the afternoon, 6-7
      repetitions, at 85% of 1 repetition maximum for 3 weeks), or a control group (n =
      10), who did not exercise during the 3 weeks. Before and after the study, an
      unstimulated saliva sample (2 ml) was taken every 2 hours for a maximum of 16
      hours during each day. A significant decrease was observed in the resistance
      exercise (44.2%, p = 0.001) and control group (46.1%, p = 0.001) for salivary
      testosterone at each time point compared with baseline (p = 0.001). There was
      also no significant difference between the exercise and resting conditions in
      both groups for salivary testosterone (p > 0.05), except a significantly higher
      increase by 38.4% vs. -0.02% (p = 0.001), at 1730 hours during exercise sessions
      in the resistance exercise group compared with the control group. Resistance
      exercise has no noteworthy effect on circadian secretion of salivary testosterone
      throughout the 16 waking hours. These results indicate that athletes can
      undertake resistance exercise in either the morning or afternoon with the
      knowledge that a similar testosterone response can be expected regardless of the
      time of day.

PMID- 25051006
TI  - Time-motion analysis of Italian elite women's basketball games: individual and
      team analyses.
AB  - The aim of this study was to assess elite women's basketball game performance.
      Five elite women's games (3 Italian first division and 2 Euroleague) were
      analyzed for individual and team time-motion analyses. The individual analysis
      evaluated the players' movement patterns with particular focus on high-intensity
      activity (HIA), sprint activity, and repeated sprint events (RSEs). Team analysis
      included live time (LT), stoppage time (ST), and their ratio, transfer (TR)
      phases, and half court and full court actions. The frequency of occurrence of
      changes of activities was n = 576 +/- 110, one every 2.56 seconds of LT. Total
      HIA was 8.5 +/- 1.8% of LT and no significant differences between quarter periods
      were observed. In general, players performed linear sprints (48.3 +/- 2.9%) over
      1-5 m distance (56.8 +/- 5.6%). The occurrence of RSE was 4.4 +/- 1.7, with 58.6
      +/- 18.5% passive recovery between sprints. Team analysis showed no significant
      difference between games for LT and ST phases (ratio = 1.18 +/- 0.25). For game
      analysis, LT and ST were 43.4 +/- 7.8% and 51.1 +/- 8.4%, respectively. A
      difference between games was found for half court actions (p < 0.01) and TR
      phases (p <= 0.05). Moreover, 1 TR and 2 TR were the most performed (45.3 and
      23.9%) actions. These results encourage coaches to include repeated sprint
      ability with mainly linear and short sprints into a comprehensive training
      program.

PMID- 25051007
TI  - Forced inspiratory volume in the first second as predictor of front-crawl
      performance in young sprint swimmers.
AB  - The purposes of this study were to determine the extent to which specific
      anthropometric, conditional, and pulmonary function variables predict 100-m front
      crawl performance in national swimmers and compare anthropometric, conditional,
      and pulmonary function variables between both genders. Two groups (male, n = 8
      and female, n = 9) of sprint swimmers (mean age +/- SD = 19.4 +/- 0.7 years and
      16.9 +/- 3.2 years, respectively) of national competitive level volunteered for
      this study. Swimmers performed an all-out 100-m front-crawl swimming test.
      Physiological parameters of lung function were measured using portable
      spirometer. Basic anthropometry included body height, body mass, and skinfold
      thickness. Lower limb strength was measured by countermovement and squat jump
      tests. Correlation and regression analyses were calculated to quantify the
      relationships between trial time and each variable potentially predictive.
      Differences between means of both gender groups were analyzed. Results showed
      that 100-m race performance correlated significantly with forced inspiratory
      volume in the first second (FIV1) in male swimmers and with FIV1 and forced vital
      capacity in female swimmers. Stepwise multiple regressions revealed that FIV1 was
      the only predictor of 100-m race performance, explaining 66% of 100-m time trial
      variance in male swimmers and 58% in female swimmers. Gender comparisons
      indicated significant differences in anthropometric, conditional, pulmonary
      function, and performance variables. The findings suggest that FIV1 could be a
      good predictor of performance and it should be evaluated routinely and used by
      coaches in front-crawl sprint swimmers.

PMID- 25051008
TI  - Novel speed test for evaluation of badminton-specific movements.
AB  - In this study, we developed a novel badminton-specific speed test (BST). The test
      was designed to mimic match play. The test starts in the center of the court and
      consists of 5 maximal actions to sensors located in each of the 4 corners of the
      court. The 20 actions are performed in randomized order as dictated by computer
      screen shots displayed 1 second after completion of the previous action. We
      assessed day-to-day variation in elite players, and specificity of the test was
      evaluated by comparing 30-m sprint performance and time to complete the BST in 20
      elite players, 21 skilled players, and 20 age-matched physical active subjects
      (non-badminton players). Sprint performance was similar across groups, whereas
      the elite players were significantly (p <= 0.05) faster in the BST (total test
      time: 32.3 +/- 1.1 seconds; average: 1.6 seconds per action) than the skilled
      (34.1 +/- 2.0 seconds) and non-badminton players (35.7 +/- 1.7 seconds). Day-to
      day coefficient of variation (CV) of the BST was 0.7% for the elite players,
      whereas CV for repeated tests on the same day was 1.7% for elite, 2.6% for
      skilled, and 2.5% for non-badminton players. On this basis, we suggest that the
      BST may be valuable for evaluation of short-term maximal movement speed in
      badminton players. Thus, the BST seems to be sport specific, as it may
      discriminate between groups (elite, less trained players, and non-badminton
      players) with similar sprinting performance, and the low test-retest variation
      may allow for using the BST to evaluate longitudinal changes, for example,
      training effects or seasonal variations.

PMID- 25051009
TI  - Direct observation of the cyclic dimer in liquid acetic acid by probing the C=O
      vibration with ultrafast coherent Raman spectroscopy.
AB  - We present a comparison of spontaneous Raman and ultrafast coherent anti-Stokes
      Raman scattering (CARS) spectra of the C=O vibration of liquid acetic acid. The
      former technique cannot clearly reveal the number of contributions in the
      spectrum. However, the additional time and spectrally resolved CARS experiment
      supports strictly the existence of four modes, which proves the coexistence of
      more than one H-bonded configuration in liquid acetic acid. A comparably slowly
      dephasing mode which is obscured by a broad band in the linear Raman spectrum is
      assigned to the cyclic dimer and can be observed freed from all other
      contributions by ultrafast CARS.

PMID- 25051010
TI  - A unified perspective on the nature of bonding in pairwise interatomic
      interactions.
AB  - Different classes of ground electronic state pairwise interatomic interactions
      are referenced to a single canonical potential using explicit transformations.
      These approaches have been applied to diatomic molecules N2, CO, H2(+), H2, HF,
      LiH, Mg2, Ca2, O2, the argon dimer, and one-dimensional cuts through
      multidimensional potentials of OC-HBr, OC-HF, OC-HCCH, OC-HCN, OC-HCl, OC-HI, OC
      BrCl, and OC-Cl2 using accurate semiempirically determined interatomic Rydberg
      Klein-Rees (RKR) and morphed intermolecular potentials. Different bonding
      categories are represented in these systems, which vary from van der Waals,
      halogen bonding, and hydrogen bonding to strongly bound covalent molecules with
      binding energies covering 3 orders of magnitude from 84.5 to 89,600.6 cm(-1) in
      ground state dissociation energies. Such approaches were then utilized to give a
      unified perspective on the nature of bonding in the whole range of diatomic and
      intermolecular interactions investigated.

PMID- 25051012
TI  - A DNA-mediated homogeneous binding assay for proteins and small molecules.
AB  - Optical detection of molecular targets typically requires immobilization,
      separation, or chemical or enzymatic processing. An important exception is
      aptamers that allow optical detection in solution based on conformational
      changes. This method, however, requires the laborious selection of aptamers with
      high target specificity and affinity, and the ability to undergo the required
      conformational changes. Here we report on an alternative generic scheme for
      detecting small molecules and proteins in solution based on a shift in the
      equilibrium of DNA-based strand displacement competition reaction. The shift
      occurs upon binding of a protein, for example, an antibody to its target. We
      demonstrate nanomolar detection of small molecules such as biotin, digoxigenin,
      vitamin D, and folate, in buffer and in plasma. The method is flexible, and we
      also show nanomolar detection of the respective antibodies or protein targets of
      these molecules. The detection scheme provides a generic alternative to aptamers
      for detection of analytes. 

PMID- 25051011
TI  - TNF-alpha mediated increase of HIF-1alpha inhibits VASP expression, which reduces
      alveolar-capillary barrier function during acute lung injury (ALI).
AB  - Acute lung injury (ALI) is an inflammatory disorder associated with reduced
      alveolar-capillary barrier function and increased pulmonary vascular
      permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated
      with all types of modulations of cytoskeleton rearrangement-dependent cellular
      morphology and function, such as adhesion, shrinkage, and permeability. The
      present studies were conducted to investigate the effects and mechanisms by which
      tumor necrosis factor-alpha (TNF-alpha) increases the tight junction permeability
      in lung tissue associated with acute lung inflammation. After incubating A549
      cells for 24 hours with different concentrations (0-100 ng/mL) of TNF-alpha, 0.1
      to 8 ng/mL TNF-alpha exhibited no significant effect on cell viability compared
      with the 0 ng/mL TNF-alpha group (control group). However, 10 ng/mL and 100 ng/mL
      TNF-alpha dramatically inhibited the viability of A549 cells compared with the
      control group (*p<0.05). Monolayer cell permeability assay results indicated that
      A549 cells incubated with 10 ng/mL TNF-alpha for 24 hours displayed significantly
      increased cell permeability (*p<0.05). Moreover, the inhibition of VASP
      expression increased the cell permeability (*p<0.05). Pretreating A549 cells with
      cobalt chloride (to mimic a hypoxia environment) increased protein expression
      level of hypoxia inducible factor-1alpha (HIF-1alpha) (*p<0.05), whereas protein
      expression level of VASP decreased significantly (*p<0.05). In LPS-induced ALI
      mice, the concentrations of TNF-alpha in lung tissues and serum significantly
      increased at one hour, and the value reached a peak at four hours. Moreover, the
      Evans Blue absorption value of the mouse lung tissues reached a peak at four
      hours. The HIF-1alpha protein expression level in mouse lung tissues increased
      significantly at four hours and eight hours (**p<0.001), whereas the VASP protein
      expression level decreased significantly (**p<0.01). Taken together, our data
      demonstrate that HIF-1alpha acts downstream of TNF-alpha to inhibit VASP
      expression and to modulate the acute pulmonary inflammation process, and these
      molecules play an important role in the impairment of the alveolar-capillary
      barrier.

PMID- 25051013
TI  - Frustrated Lewis pair-mediated C-O or C-H bond activation of ethers.
AB  - Protocols for the FLP-mediated transformation of ethers are presented. Distinct
      reaction pathways involving either C-O or C-H bond activation occur depending on
      the application of oxophilic B(C6F5)3 or hydridophilic tritylium ions as the
      Lewis acid. 

PMID- 25051014
TI  - Terahertz science and technology of carbon nanomaterials.
AB  - The diverse applications of terahertz (THz) radiation and its importance to
      fundamental science makes finding ways to generate, manipulate and detect THz
      radiation one of the key areas of modern applied physics. One approach is to
      utilize carbon nanomaterials, in particular, single-wall carbon nanotubes and
      graphene. Their novel optical and electronic properties offer much promise to the
      field of THz science and technology. This article describes the past, current,
      and future of THz science and technology of carbon nanotubes and graphene. We
      will review fundamental studies such as THz dynamic conductivity, THz
      nonlinearities and ultrafast carrier dynamics as well as THz applications such as
      THz sources, detectors, modulators, antennas and polarizers. 

PMID- 25051015
TI  - 4-Amino-2-trifluoromethyl-phenyl retinate inhibits the migration of BGC-823 human
      gastric cancer cells by downregulating the phosphorylation level of MLC II.
AB  - 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR) is a novel all-trans retinoic
      acid (ATRA) derivative which was reported to have a superior antitumor effect in
      breast cancer cells. However, little is known about its antitumor effects on
      human gastric cancer cells and the mechanisms have not been fully elucidated. The
      results of the present study suggest that in the human gastric carcinoma cell
      line BGC-823, ATPR plays a more effective role than ATRA at the same dose in
      inhibiting proliferation, migration and inducing differentiation after the same
      treatment time. Furthermore, we investigated the preliminary mechanism of ATPR's
      anti-migration effect. Immunofluorescence assay demonstrated that claudin-18
      positioned from cytoplasm to cell surface following ATPR stimuli. Real-time
      quantitative RT-PCR and western blot analyses showed that ATPR had significant
      effects on downregulation of the phosphorylation level of myosin light chain II
      (MLC II) by suppressing myosin light chain kinase (MLCK) and Rho-associated
      coiled-coil containing kinase (ROCK), as well as its regulation in the protein
      expression of RARalpha and RARbeta. Moreover, ATPR increased the activity of
      myosin phosphatase by inhibiting ROCK. Consequently, ATPR showed more promising
      antitumor effects than ATRA in BGC-823 in vitro, and it may conduct its anti
      migration effects by decreasing the phosphorylation level of MLC II, as well as
      by regulating MLCK and ROCK as downstream target genes. 

PMID- 25051016
TI  - Ezrin is required for epithelial-mesenchymal transition induced by TGF-beta1 in
      A549 cells.
AB  - Epithelial mesenchymal transition (EMT) has been shown to play a role in cellular
      differentiation during deve-lopment and tumor invasion. However, the precise
      molecular mechanisms of EMT are not fully elucidated. Previous studies suggested
      that the mechanism underlying the possible involvement of ezrin in EMT process
      might be different from that of moesin, another ERM protein. In our study, we
      examined the role of ezrin in actin filament reorganization and cell meta-stasis
      during TGF-beta1-induced alveolar EMT. Suppressing ezrin expression limited
      morphological changes and actin filament remodeling, decreased cell migration and
      invasion during EMT. Immunofluorescence experiments indicated that EMT
      characteristics in lung cancer cells are associated to differential ezrin
      subcellular localization. We also found that podocalyxin interacted with ezrin
      after TGF-beta1 induction. Therefore, ezrin is an important regulator of the EMT
      process, and its function might possibly be mediated by the ezrin-podocalyxin
      interaction during TGF-beta1-induced alveolar EMT. Our finding provides important
      new insights into the mechanisms of action of the ERM proteins in the TGF-beta1
      induced alveolar EMT. 

PMID- 25051017
TI  - Diaporine, a novel endophyte-derived regulator of macrophage differentiation.
AB  - Diaporine (1), an unprecedented symmetric polyketide, was characterized from the
      endophytic fungus. The structure was determined by extensive spectroscopic
      analyses. Diaporine can inhibit significantly the differentiation of macrophages
      and has potential to induce conversion from the M2 to the M1 phenotype, in
      addition to regulation of the TLR4-MAPK signal pathway and PPARgamma activity.

PMID- 25051018
TI  - CYP3A4*22 and CYP3A5*3 are associated with increased levels of plasma simvastatin
      concentrations in the cholesterol and pharmacogenetics study cohort.
AB  - OBJECTIVE: Simvastatin is primarily metabolized by CYP3A4. A combined CYP3A4/5
      genotype classification, combining the decrease-of-function CYP3A4*22 and the
      loss-of-function CYP3A5*3, has recently been reported. We aim to determine
      whether CYP3A4*22 and CYP3A5*3 alleles are associated with increased plasma
      concentrations of simvastatin lactone (SV) and simvastatin acid (SVA). This is
      the first report evaluating associations between in-vivo simvastatin
      concentrations and CYP3A4*22, alone or in a combined CYP3A4/5 genotype-defined
      classification. PARTICIPANTS AND METHODS: Genotypes and simvastatin
      concentrations were determined for 830 participants (555 Whites and 275 African
      Americans) in the Cholesterol and Pharmacogenomics clinical trial with 40 mg/day
      simvastatin for 6 weeks. Concentrations were determined in 12-h postdose samples.
      Associations between simvastatin concentrations and CYP3A4*22 and CYP3A5*3
      alleles were tested separately and in a combined CYP3A4/5 genotype-defined
      classification system. RESULTS: In Whites, CYP3A4*22 carriers (n=42) had 14%
      higher SVA (P=0.04) and 20% higher SV (P=0.06) compared with noncarriers (n=513).
      CYP3A5*3 allele status was not significantly associated with SV or SVA in Whites.
      In African-Americans, CYP3A4*22 carriers (n=8) had 170% higher SV (P<0.01) than
      noncarriers (n=267), but no significant difference was detected for SVA. African
      American CYP3A5 nonexpressors (n=28) had 33% higher SV (P=0.02) than CYP3A5
      expressors (n=247), but no significant difference was detected for SVA. For both
      races, SV appeared to decrease across the rank-ordered combined CYP3A4/5 genotype
      defined groups (poor, intermediate, and extensive metabolizers); however, similar
      trends were not observed for SVA. CONCLUSION: Genetic variation in CYP3A4 was
      associated with plasma simvastatin concentrations in self-reported Whites.
      Genetic variations in CYP3A4 and CYP3A5 were associated with plasma simvastatin
      concentrations in self-reported African-Americans.

PMID- 25051019
TI  - Osteogenic potential for replacing cells in rat cranial defects implanted with a
      DNA/protamine complex paste.
AB  - Osteoinductive scaffolds are required for bone tissue engineering. The aim of the
      present study was to assess the osteoinductive capacity of deoxyribonucleic acid
      (DNA)/protamine complexes in a rat model of critical-size calvarial defects. In
      addition, we investigated whether cultured mesenchymal-like cells (DP-cells)
      outgrown from DNA/protamine complex engrafted defects could differentiate to
      become osteogenic cells in vitro. DNA/protamine complexes were prepared by
      reactions between DNA and protamine sulfate solutions with stirring. Critical
      sized (8mm) calvarial defects were created in the central parietal bones of adult
      rats. Defects were either left empty or treated with DNA/protamine complex
      scaffolds. Subsequently, micro-computed tomography (micro-CT), histological, and
      immunohistochemical analyses were performed. Micro-CT and histological assays
      showed that DNA/protamine complex engrafted defects had enhanced bone
      regeneration. DP-cells were expanded from explants of DNA/protamine complex
      engrafted defects using an explant outgrowth culture system. Osteogenesis-related
      factors were assessed in DP-cells after treatment with an osteoblast-inducing
      reagent (OIR). After 3months, nearly complete healing was observed for
      DNA/protamine complex engrafted calvarial defects. Increased alkaline phosphatase
      (ALP) activity and Alizarin red staining were found for cultured DP-cells. These
      cells had high expression levels of osteogenic genes, including those for RUNX-2,
      ALP, osteopontin, and osteocalcin. These results indicated that DNA/protamine
      complexes could facilitate bone regeneration in calvarial defects. Moreover, in
      vitro osteogenic induction experiments showed that DP-cells outgrown from
      DNA/protamine engrafted defects had an osteogenic potential. Based on these
      results, we suggest that DNA/protamine complexes may recruit osteocompetent cells
      in these defects, where they differentiate to osteogenic cells. 

PMID- 25051020
TI  - Distal two-bond versus three-bond electronegative oxo-substituent effect controls
      the kinetics and thermodynamics of the conversion of a C-nitroso function to the
      corresponding oxime in the conformationally locked pentofuranose
      (bicyclo[2.2.1]heptane) system.
AB  - We report the high-yielding and scalable diastereospecific synthesis of isomeric
      bicyclo[2.2.1]heptane-7- and -8-oximes and their corresponding C-nitroso
      derivatives, which are the key intermediates for the synthesis of
      carbanucleosides. Neither the (C7-R)-nitroso- nor (C8-S)-nitrosobicycloheptane
      system requires any external base in DMSO-d6 to afford the corresponding oxime,
      and no reverse isomerization from the oxime to the C-nitroso compound was
      observed. The conversion of the (C8-S)-nitroso compound to the E/Z-oximes was ~8
      times faster (at 40  degrees C) than that of the (C7-R)-nitroso derivative. The
      mechanism involves first-order reaction kinetics for the conversion of either the
      (C7-R)- or (C8-S)-nitroso derivative to the corresponding E/Z-oximes. The lower
      rate of conversion of the (C7-R)-nitroso compound to the corresponding oximes
      compared with that of the (C8-S)-nitroso derivative is attributed to the fact
      that the acidic H8 ionizing center is two bonds away from the OPMB group on C1 in
      the latter whereas H7 is three bonds away from the C1 OMe group in the former,
      making the effect of the electron-withdrawing group on C1 stronger in the latter.

PMID- 25051021
TI  - Impact of histological variants on the outcomes of nonmuscle invasive bladder
      cancer after transurethral resection.
AB  - PURPOSE OF REVIEW: The scoring system used after transurethral resection of the
      bladder (TURB) to guide clinical decision-making regarding nonmuscle invasive
      bladder cancer (NMIBC) largely assumes that NMIBCs are pure urothelial carcinomas
      and does not take into account the role of variant histology. This review
      outlines pathological and clinical characteristics of major histological variants
      to determine their potential impact in therapeutic strategies for the management
      of NMIBC. RECENT FINDINGS: Assessing the presence of histological variants in
      NMIBCs after TURB currently remains challenging because of limited tissue sample
      sizes. However, the presence of these variants often indicates poor prognosis
      with increased risk for recurrence and progression. Among them, only the
      following histological variants are indications for Bacillus Calmette-Guerin
      intravesical instillations: squamous or glandular differentiations and
      deceptively benign or lymphoepithelioma-like carcinomas. However, patients
      diagnosed with any other variants should be promptly considered for early radical
      cystectomy, and only those with small cell carcinoma might benefit from
      neoadjuvant chemotherapy with a neuroendocrine-specific regimen. SUMMARY: Based
      on the available literature (e.g., small case studies and retrospective studies),
      the existence of histological variants after TURB appears to massively impact
      NMIBC outcomes.

PMID- 25051022
TI  - Thermal ablation in renal cell carcinoma management: a comprehensive review.
AB  - PURPOSE OF REVIEW: This article provides an overview of recent developments in
      the field of thermal ablation for renal cell carcinoma and focuses on current
      standard techniques, new technologies, imaging for ablation guidance and
      evaluation, and future perspectives. RECENT FINDINGS: Emerging long-term data on
      cryoablation and radiofrequency ablation (RFA) show marginally lower oncologic
      outcomes compared to surgical treatment, balanced by better functional and
      perioperative outcomes. Reports on residual disease vary widely, influenced by
      different definitions and strategies in determining ablation failure. Stratifying
      disease-free survival after RFA according to tumor size suggests 3 cm to be a
      reasonable cut off for RFA tumor selection. Microwave ablation and high-intensity
      focal ultrasound are modalities with the potential of creating localized high
      temperatures. However, difficulties in renal implementation are impairing
      sufficient ablation results. Irreversible electroporation, although not strictly
      thermal, is a new technology showing promising results in animal and early human
      research. SUMMARY: Although high-level randomized controlled trials comparing
      thermal ablation techniques are lacking, evidence shows that thermal ablation for
      small renal masses is a safe procedure for both long-term oncologic and
      functional outcomes. Thermal ablation continues to be associated with a low risk
      of residual disease, for which candidates should be properly informed. RFA and
      cryoablation remain the standard techniques whereas alternative techniques
      require further studies.

PMID- 25051023
TI  - Nephrometry scoring systems for surgical decision-making in nephron-sparing
      surgery.
AB  - PURPOSE OF REVIEW: Herein, we review the various recently published nephrometry
      scoring systems and the available data on their ability to predict clinical
      outcomes and their usefulness for new operative techniques. RECENT FINDINGS:
      Several studies showed that the preoperative aspects and dimensions used for
      anatomical classification score, the RENAL system, and the centrality index are
      reproducible and able to predict certain clinical intraoperative and
      postoperative variables in patients undergoing nephron-sparing surgery. Addition
      of variables, such as the BMI, to the pre-existing scores might improve their
      predictive abilities. SUMMARY: Nephrometry scoring systems may allow better
      preoperative planning and counseling of patients. If they gain widespread use in
      clinical practice, they may also help to give reliable comparisons of morbidity
      rates among different partial nephrectomy techniques, individual surgeons, and
      institutions.

PMID- 25051024
TI  - Noncoding RNA in bladder cancer: a specific focus upon high-risk nonmuscle
      invasive disease.
AB  - PURPOSE OF REVIEW: Bladder cancer is a common disease whose natural history can
      be unpredictable. As such, there is an urgent clinical need to identify
      biomarkers that will improve the care of patients by allowing a more
      individualized approach. Noncoding RNAs (ncRNAs) are a recently identified
      subgroup of RNAs whose mature species are not translated into proteins. Here, we
      review knowledge of ncRNA in bladder cancer, with a focus upon their role in high
      risk nonmuscle invasive tumors. RECENT FINDINGS: There have been a number of
      articles reporting the ability of microRNAs to help evaluate patients with
      nonmuscle invasive bladder cancer. New long ncRNA species have been evaluated for
      the first time in bladder cancer. Competing endogenous RNAs and enhancer RNAs
      show interesting functional and regulatory effects in other cancers, but have yet
      to be evaluated in bladder cancer. SUMMARY: Novel RNA species are increasingly
      being used to help prognosticate patients with bladder cancer and to understand
      key oncological events in the evolution of this disease. Future work is needed to
      validate potential clinical utility of the RNA species described.

PMID- 25051025
TI  - New imaging techniques for nonmuscle invasive bladder cancer.
AB  - PURPOSE OF REVIEW: Recent advances in imaging techniques provide innovative tools
      for the detection of bladder cancer. In patients with nonmuscle invasive cancer,
      there is a need for enhanced visualization of flat growing lesions and multifocal
      tumors. The aim of new imaging modalities is the improved detection and staging
      of bladder lesions, as an adjunct to conventional white light endoscopy. RECENT
      FINDINGS: Fluorescence cystoscopy with 5-aminolevulinic acid and
      hexaminolevulinate has been shown to improve the detection of papillary and flat
      bladder lesions in comparison to conventional white light cystoscopy. Prospective
      phase III clinical trials have demonstrated advanced diagnostic ability, enhanced
      tumor resection, and reduced tumor recurrence. Molecular targets for photodynamic
      diagnosis are currently under investigation. Narrow band imaging has gained in
      popularity because of its availability in both flexible and rigid cystoscopy and
      ureteroscopy and its potential for detection of carcinoma in situ. Emerging
      endomicroscopic technologies such as optical coherence tomography, confocal laser
      endomicroscopy, and Raman spectroscopy introduce real-time histologic imaging
      during the procedure. SUMMARY: While scientific evidence supports macroscopic
      applications, such as photodynamic diagnosis or narrow band imaging, and their
      progressive implementation in the clinical workflow, further studies are needed
      to identify the adjunct endomicroscopic technology optimal for enhanced accuracy
      and utility.

PMID- 25051026
TI  - beta-l-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (l
      BHDU) prevents varicella-zoster virus replication in a SCID-Hu mouse model and
      does not interfere with 5-fluorouracil catabolism.
AB  - The alphaherpesvirus varicella-zoster virus (VZV) causes chickenpox and shingles.
      Current treatments are acyclovir (ACV) and its derivatives, foscarnet and
      brivudine (BVdU). Additional antiviral compounds with increased potency and
      specificity are needed to treat VZV, especially to treat post-herpetic neuralgia.
      We evaluated beta-l-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)]
      uracil (l-BHDU, 1) and 5'-O-valyl-l-BHDU (2) in three models of VZV replication:
      primary human foreskin fibroblasts (HFFs), skin organ culture (SOC) and in SCID
      Hu mice with skin xenografts. The efficacy of l-BHDU in vivo and its drug-drug
      interactions were previously not known. In HFFs, 200MUM l-BHDU was noncytotoxic
      over 3days, and l-BHDU treatment reduced VZV genome copy number and cell to cell
      spread. The EC50 in HFFs for l-BHDU and valyl-l-BHDU were 0.22 and 0.03MUM,
      respectively. However, l-BHDU antagonized the activity of ACV, BVdU and foscarnet
      in cultured cells. Given its similar structure to BVdU, we asked if l-BHDU, like
      BVdU, inhibits 5-fluorouracil catabolism. BALB/c mice were treated with 5-FU
      alone or in combination with l-BHDU or BVdU. l-BHDU did not interfere with 5-FU
      catabolism. In SCID-Hu mice implanted with human skin xenografts, l-BHDU and
      valyl-l-BHDU were superior to ACV and valacyclovir. The maximum concentration
      (Cmax) levels of l-BHDU were determined in mouse and human tissues at 2h after
      dosing, and comparison of concentration ratios of tissue to plasma indicated
      saturation of uptake at the highest dose. For the first time, an l-nucleoside
      analog, l-BHDU, was found to be effective and well tolerated in mice. 

PMID- 25051028
TI  - A hybrid spatio-temporal data indexing method for trajectory databases.
AB  - In recent years, there has been tremendous growth in the field of indoor and
      outdoor positioning sensors continuously producing huge volumes of trajectory
      data that has been used in many fields such as location-based services or
      location intelligence. Trajectory data is massively increased and semantically
      complicated, which poses a great challenge on spatio-temporal data indexing. This
      paper proposes a spatio-temporal data indexing method, named HBSTR-tree, which is
      a hybrid index structure comprising spatio-temporal R-tree, B*-tree and Hash
      table. To improve the index generation efficiency, rather than directly inserting
      trajectory points, we group consecutive trajectory points as nodes according to
      their spatio-temporal semantics and then insert them into spatio-temporal R-tree
      as leaf nodes. Hash table is used to manage the latest leaf nodes to reduce the
      frequency of insertion. A new spatio-temporal interval criterion and a new node
      choosing sub-algorithm are also proposed to optimize spatio-temporal R-tree
      structures. In addition, a B*-tree sub-index of leaf nodes is built to query the
      trajectories of targeted objects efficiently. Furthermore, a database storage
      scheme based on a NoSQL-type DBMS is also proposed for the purpose of cloud
      storage. Experimental results prove that HBSTR-tree outperforms TB*-tree in some
      aspects such as generation efficiency, query performance and query type. 

PMID- 25051029
TI  - A bionic camera-based polarization navigation sensor.
AB  - Navigation and positioning technology is closely related to our routine life
      activities, from travel to aerospace. Recently it has been found that Cataglyphis
      (a kind of desert ant) is able to detect the polarization direction of skylight
      and navigate according to this information. This paper presents a real-time
      bionic camera-based polarization navigation sensor. This sensor has two work
      modes: one is a single-point measurement mode and the other is a multi-point
      measurement mode. An indoor calibration experiment of the sensor has been done
      under a beam of standard polarized light. The experiment results show that after
      noise reduction the accuracy of the sensor can reach up to 0.3256 degrees . It is
      also compared with GPS and INS (Inertial Navigation System) in the single-point
      measurement mode through an outdoor experiment. Through time compensation and
      location compensation, the sensor can be a useful alternative to GPS and INS. In
      addition, the sensor also can measure the polarization distribution pattern when
      it works in multi-point measurement mode.

PMID- 25051027
TI  - A whole recombinant yeast-based therapeutic vaccine elicits HBV X, S and Core
      specific T cells in mice and activates human T cells recognizing epitopes linked
      to viral clearance.
AB  - Chronic hepatitis B infection (CHB) is characterized by sub-optimal T cell
      responses to viral antigens. A therapeutic vaccine capable of restoring these
      immune responses could potentially improve HBsAg seroconversion rates in the
      setting of direct acting antiviral therapies. A yeast-based immunotherapy
      (Tarmogen) platform was used to make a vaccine candidate expressing hepatitis B
      virus (HBV) X, surface (S), and Core antigens (X-S-Core). Murine and human
      immunogenicity models were used to evaluate the type and magnitude of HBV-Ag
      specific T cell responses elicited by the vaccine. C57BL/6J, BALB/c, and HLA
      A*0201 transgenic mice immunized with yeast expressing X-S-Core showed T cell
      responses to X, S and Core when evaluated by lymphocyte proliferation assay,
      ELISpot, intracellular cytokine staining (ICS), or tumor challenge assays. Both
      CD4+ and CD8+ T cell responses were observed. Human T cells transduced with HBc18
      27 and HBs183-91 specific T cell receptors (TCRs) produced interferon gamma
      (IFNgamma following incubation with X-S-Core-pulsed dendritic cells (DCs).
      Furthermore, stimulation of peripheral blood mononuclear cells (PBMCs) isolated
      from CHB patients or from HBV vaccine recipients with autologous DCs pulsed with
      X-S-Core or a related product (S-Core) resulted in pronounced expansions of HBV
      Ag-specific T cells possessing a cytolytic phenotype. These data indicate that X
      S-Core-expressing yeast elicit functional adaptive immune responses and supports
      the ongoing evaluation of this therapeutic vaccine in patients with CHB to
      enhance the induction of HBV-specific T cell responses. 

PMID- 25051030
TI  - On bandwidth characteristics of tuning fork micro-gyroscope with mechanically
      coupled sense mode.
AB  - The bandwidth characteristics of a tuning fork micro-gyroscope with mechanically
      coupled sense mode were investigated in this paper to provide some references for
      mechanical bandwidth design. The concept of sense mode mechanical coupling is
      introduced first. Theoretical frequency response analyses were then carried out
      on the mechanical part of the gyroscope. Equations representing the relationships
      between the differential output signal and the frequency of the input angular
      rate were deduced in full frequency range and further simplified in low frequency
      range. Based on these equations, bandwidth characteristics under ideal and non
      ideal conditions are discussed. Analytical results show that under ideal
      conditions, the bandwidth characteristics of a tuning fork micro-gyroscope are
      similar to those of a single mass micro-gyroscope, but under non-ideal
      conditions, especially when sense mass and/or stiffness are asymmetric, the
      bandwidth characteristics would be quite different because the in-phase mode
      would participate in the anti-phase vibration response. Experimental
      verifications were carried out on two micro-gyroscope prototypes designed in our
      laboratory. The deduced equations and analytical results can be used in guiding
      the mechanical bandwidth design of tuning fork micro-gyroscopes with mechanically
      coupled sense mode. 

PMID- 25051031
TI  - Reduction of the dimensionality of the EEG channels during scoliosis correction
      surgeries using a wavelet decomposition technique.
AB  - This paper presents a comparison between the electroencephalogram (EEG) channels
      during scoliosis correction surgeries. Surgeons use many hand tools and
      electronic devices that directly affect the EEG channels. These noises do not
      affect the EEG channels uniformly. This research provides a complete system to
      find the least affected channel by the noise. The presented system consists of
      five stages: filtering, wavelet decomposing (Level 4), processing the signal
      bands using four different criteria (mean, energy, entropy and standard
      deviation), finding the useful channel according to the criteria's value and,
      finally, generating a combinational signal from Channels 1 and 2. Experimentally,
      two channels of EEG data were recorded from six patients who underwent scoliosis
      correction surgeries in the Pusat Perubatan Universiti Kebangsaan Malaysia
      (PPUKM) (the Medical center of National University of Malaysia). The
      combinational signal was tested by power spectral density, cross-correlation
      function and wavelet coherence. The experimental results show that the system
      outputted EEG signals are neatly switched without any substantial changes in the
      consistency of EEG components. This paper provides an efficient procedure for
      analyzing EEG signals in order to avoid averaging the channels that lead to
      redistribution of the noise on both channels, reducing the dimensionality of the
      EEG features and preparing the best EEG stream for the classification and
      monitoring stage. 

PMID- 25051032
TI  - Influence of segmentation of ring-shaped NdFeB magnets with parallel
      magnetization on cylindrical actuators.
AB  - This work analyses the effects of segmentation followed by parallel magnetization
      of ring-shaped NdFeB permanent magnets used in slotless cylindrical linear
      actuators. The main purpose of the work is to evaluate the effects of that
      segmentation on the performance of the actuator and to present a general overview
      of the influence of parallel magnetization by varying the number of segments and
      comparing the results with ideal radially magnetized rings. The analysis is first
      performed by modelling mathematically the radial and circumferential components
      of magnetization for both radial and parallel magnetizations, followed by an
      analysis carried out by means of the 3D finite element method. Results obtained
      from the models are validated by measuring radial and tangential components of
      magnetic flux distribution in the air gap on a prototype which employs magnet
      rings with eight segments each with parallel magnetization. The axial force
      produced by the actuator was also measured and compared with the results obtained
      from numerical models. Although this analysis focused on a specific topology of
      cylindrical actuator, the observed effects on the topology could be extended to
      others in which surface-mounted permanent magnets are employed, including
      rotating electrical machines. 

PMID- 25051033
TI  - An optical fibre-based sensor for respiratory monitoring.
AB  - In this paper, a textile-based respiratory sensing system is presented. Highly
      flexible polymeric optical fibres (POFs) that react to applied pressure were
      integrated into a carrier fabric to form a wearable sensing system. After the
      evaluation of different optical fibres, different setups were compared. To
      demonstrate the feasibility of such a wearable sensor, the setup featuring the
      best performance was placed on the human torso, and thus it was possible to
      measure the respiratory rate. Furthermore, we show that such a wearable system
      enables to keep track of the way of breathing (diaphragmatic, upper costal and
      mixed) when the sensor is placed at different positions of the torso. A
      comparison of the results with the output of some commercial respiratory
      measurements devices confirmed the utility of such a monitoring device. 

PMID- 25051034
TI  - A new electrochemical sensor based on task-specific ionic liquids-modified palm
      shell activated carbon for the determination of mercury in water samples.
AB  - In this study, a potentiometric sensor composed of palm shell activated carbon
      modified with trioctylmethylammonium thiosalicylate (TOMATS) was used for the
      potentiometric determination of mercury ions in water samples. The proposed
      potentiometric sensor has good operating characteristics towards Hg (II),
      including a relatively high selectivity; a Nernstian response to Hg (II) ions in
      a concentration range of 1.0 * 10(-9) to 1.0 * 10(-2) M, with a detection limit
      of 1 * 10(-10) M and a slope of 44.08 +/- 1.0 mV/decade; and a fast response time
      (~5 s). No significant changes in electrode potential were observed when the pH
      was varied over the range of 3-9. Additionally, the proposed electrode was
      characterized by good selectivity towards Hg (II) and no significant
      interferences from other cationic or anionic species.

PMID- 25051035
TI  - Distributed power-line outage detection based on wide area measurement system.
AB  - In modern power grids, the fast and reliable detection of power-line outages is
      an important functionality, which prevents cascading failures and facilitates an
      accurate state estimation to monitor the real-time conditions of the grids.
      However, most of the existing approaches for outage detection suffer from two
      drawbacks, namely: (i) high computational complexity; and (ii) relying on a
      centralized means of implementation. The high computational complexity limits the
      practical usage of outage detection only for the case of single-line or double
      line outages. Meanwhile, the centralized means of implementation raises security
      and privacy issues. Considering these drawbacks, the present paper proposes a
      distributed framework, which carries out in-network information processing and
      only shares estimates on boundaries with the neighboring control areas. This
      novel framework relies on a convex-relaxed formulation of the line outage
      detection problem and leverages the alternating direction method of multipliers
      (ADMM) for its distributed solution. The proposed framework invokes a low
      computational complexity, requiring only linear and simple matrix-vector
      operations. We also extend this framework to incorporate the sparse property of
      the measurement matrix and employ the LSQRalgorithm to enable a warm start, which
      further accelerates the algorithm. Analysis and simulation tests validate the
      correctness and effectiveness of the proposed approaches.

PMID- 25051036
TI  - An Aligned-Gap and Centered-Gap Rectangular Multiple Split Ring Resonator for
      dielectric sensing applications.
AB  - This paper presents the design and development of a planar Aligned-Gap and
      Centered-Gap Rectangular Multiple Split Ring Resonator (SRR) for microwave
      sensors that operates at a resonance frequency around 5 GHz. The sensor consists
      of a microstrip transmission line loaded with two elements of rectangular SRR on
      both sides. The proposed metamaterial sensors were designed and fabricated on
      Rogers RT5880 substrate having dielectric constant of 2.2 and thickness of 0.787
      mm. The final dimension of the proposed sensor was measured at 35 * 14 mm2.
      Measured results show good agreement with simulated ones as well as exhibiting
      high Q-factor for use in sensing application. A remarkably shift of resonance
      frequency is observed upon introduction of several sample with different
      dielectric value. 

PMID- 25051037
TI  - An integrated environment monitoring system for underground coal mines--Wireless
      Sensor Network subsystem with multi-parameter monitoring.
AB  - Environment monitoring is important for the safety of underground coal mine
      production, and it is also an important application of Wireless Sensor Networks
      (WSNs). We put forward an integrated environment monitoring system for
      underground coal mine, which uses the existing Cable Monitoring System (CMS) as
      the main body and the WSN with multi-parameter monitoring as the supplementary
      technique. As CMS techniques are mature, this paper mainly focuses on the WSN and
      the interconnection between the WSN and the CMS. In order to implement the WSN
      for underground coal mines, two work modes are designed: periodic inspection and
      interrupt service; the relevant supporting technologies, such as routing
      mechanism, collision avoidance, data aggregation, interconnection with the CMS,
      etc., are proposed and analyzed. As WSN nodes are limited in energy supply,
      calculation and processing power, an integrated network management scheme is
      designed in four aspects, i.e., topology management, location management, energy
      management and fault management. Experiments were carried out both in a
      laboratory and in a real underground coal mine. The test results indicate that
      the proposed integrated environment monitoring system for underground coal mines
      is feasible and all designs performed well as expected. 

PMID- 25051038
TI  - Deletion of the membrane protein Lmo0412 increases the virulence of Listeria
      monocytogenes.
AB  - Listeria monocytogenes is a facultative intracellular pathogen that causes
      gastroenteritis, meningitis, encephalitis and maternofetal infections. 20-30% of
      eubacterial ORFs are predicted to encode membrane proteins. The bacterial
      cytoplasmic membrane is a macromolecular structure, which plays a key role for
      the pathogenesis. Despite this, little knowledge exists regarding the function of
      cytoplasmic membrane proteins of Listeria during infection. Here, we investigated
      a predicted membrane protein of the pathogen L. monocytogenes, Lmo0412, of
      unknown function. Lmo0412 is only present in the Listeria genus and low conserved
      in the non-pathogenic species L. innocua. Bacterial fractionation and western
      blot analyses showed that Lmo0412 was only detectable in the membrane of L.
      monocytogenes EGDe during logarithmic growth phase. lmo0412 expression in L.
      monocytogenes was down-regulated during in vitro infection of JEG-3 epithelial
      cells. An L. monocytogenes mutant deficient in this membrane protein showed
      increased invasion of Caco-2 and NRK-49F host cells using in vitro infection
      models. Moreover, the lack of Lmo0412 in this deletion mutant increased the
      viable bacteria counts in the spleen and liver of mice compared to the wild type
      strain. Taken together, these data suggest a selective advantage conferred by the
      absence of Lmo0412 for the virulence of L. monocytogenes.

PMID- 25051039
TI  - Histological spectrum of cutaneous herpes infections.
AB  - Herpes simplex virus and varicella zoster virus are double-stranded DNA viruses
      that commonly infect humans, resulting in cutaneous manifestations. Diagnosis is
      generally made based on clinical findings; however, when the presentation is
      atypical, biopsy can aid in making a correct diagnosis. The classic
      histopathological findings of herpetic infection are well established
      (acantholysis, ballooning degeneration, intranuclear inclusions, multinucleation,
      necrosis, and formation of vesicles or ulcers). Herpes infection can also cause
      histopathological changes in many dermal structures. Furthermore, herpes can
      masquerade as a variety of hematologic malignancies or benign cutaneous
      conditions. The histopathological spectrum of herpes infections is reviewed and
      discussed.

PMID- 25051040
TI  - Melanoma in children, adolescents, and young adults: a clinical pathological
      study in a Brazilian population.
AB  - Malignant melanoma in children, adolescents, and young adults is unusual,
      especially before puberty. In children (age, 0-14 years), most primary lesions
      are thick and atypical (amelanotic, simulating pyogenic granuloma). In the
      population of adolescents and young adults (age, 15-39 years), melanoma is the
      third most common cancer, only behind lymphoma and breast cancer. Our study
      investigated the records of 89 patients diagnosed with cutaneous melanoma at age
      0-39 years at Hospital das Clinicas, Medical School, University of Sao Paulo
      between 1992 and 2002. They were divided into group A (0-14 years of age) and
      group B (15-39 years of age). The histopathology of all cases was reexamined.
      Statistical analysis of the data presented was performed, and the obtained data
      were compared with the literature. The frequency of melanoma in the group aged 15
      39 years was higher in women, and the most affected site was the trunk.
      Additionally, melanomas were more frequent at an earlier age in patients with
      family history of melanoma (P = 0.014). Most cases were diagnosed, at
      histopathology, as superficial spreading melanoma. Thick nodular melanomas with
      Breslow values higher than 2 mm were associated with lymph node metastasis (P <
      0.05). Our study revealed that melanoma in children, adolescents, and young
      adults may present peculiar behavior and outcome, which might reflect the genetic
      and yet not fully unraveled pathogenesis of this complex disease.

PMID- 25051041
TI  - Desmoplastic nevus of chronically sun-damaged skin: an entity to be distinguished
      from desmoplastic melanoma.
AB  - Desmoplastic (sclerotic) nevus (DSN) can often be difficult to differentiate from
      desmoplastic melanoma (DM). This can be especially difficult when DSNs occur in a
      background of heavy solar elastosis. We have observed numerous examples of DSNs
      occurring in chronically sun-damaged (CSD) skin. In a subset of these cases, we
      have observed notable pleomorphism and nuclear atypia raising concern for the
      possibility of DM. In this study, we evaluated the clinical, histopathologic, and
      immunohistochemical findings in 23 cases of DSN occurring in CSD skin and
      compared them with 10 cases of DM. DSN on CSD skin is seen in adults (mean, 53.2
      years) with a female predominance (70%) and upper (57%) and lower (17%) extremity
      anatomic locations. Most DSNs present as small flesh-colored macules or papules.
      Typical histologic features include symmetry, limited junctional growth, presence
      of a lentiginous component often with focal and limited pagetoid spread
      (extension across only a few rete ridges), and lack of deep extension. DSN and DM
      had a statistically significant difference in immunohistochemical staining for
      Melan-A and p75. Melan-A was positive in 18 of 20 DSNs and only 2 out of 10 DMs,
      whereas p75 was positive in all DMs (10/10) and was weakly positive in 11 of 20
      DSN cases. We believe that our study offers some useful clinical, histologic, and
      immunohistochemical clues to help differentiate DSNs on CSD skin from DMs.

PMID- 25051042
TI  - Multiple scattered erythematous nodules and ulcerations: challenge.

PMID- 25051043
TI  - Foamy cell angiosarcoma is a diagnostic pitfall: a case report of an angiosarcoma
      mimicking xanthoma.
AB  - The authors report a case of cutaneous angiosarcoma, composed predominantly of
      cytologically bland foamy cells, mimicking cutaneous xanthoma, dermal clear cell
      mesenchymal neoplasm, or clear cell dermatofibroma. The tumor occurred on the
      forehead and scalp of an 86-year-old white man with no history of radiation
      exposure. The tumor cells were positive for CD31, CD34, D2-40, FLI-1, and ERG,
      and were negative for CD68 and CD163. Conventional vasoformative areas, with
      atypia and mitoses that led to the correct final diagnosis, were found only in 1
      of the 2 performed biopsies. Foamy cell angiosarcoma is probably one of the least
      common variants of cutaneous angiosarcoma and represents an important diagnostic
      pitfall.

PMID- 25051044
TI  - Multiple scattered erythematous nodules and ulcerations: answer.

PMID- 25051045
TI  - Cutaneous ciliated cyst of the scalp: a case report of a cutaneous ciliated
      eccrine cyst and a brief review of the literature.
AB  - Cutaneous ciliated cysts (CCC) are rare benign cysts known to occur in the lower
      extremities of females of reproductive age. Currently, there are 2 theories that
      attempt to explain the histogenesis of this rare entity. The theory of Mullerian
      heterotopia provides a plausible histogenetic explanation for the vast majority
      of CCC. A proposed alternative theory is the ciliated metaplasia of eccrine
      glands. We believe that previously reported cases of CCC include 2 distinct
      entities. We report, herein, the first case reported in the literature of a
      cutaneous ciliated eccrine cyst occurring on the scalp.

PMID- 25051046
TI  - Fabrication of single cylindrical Au-coated nanopores with non-homogeneous fixed
      charge distribution exhibiting high current rectifications.
AB  - We designed and characterized a cylindrical nanopore that exhibits high
      electrochemical current rectification ratios at low and intermediate electrolyte
      concentrations. For this purpose, the track-etched single cylindrical nanopore in
      polymer membrane was coated with a gold (Au) layer via electroless plating
      technique. Then, a non-homogeneous fixed charge distribution inside the Au-coated
      nanopore was obtained by incorporating thiol-terminated uncharged poly(N
      isopropylacrylamide) chains in series to poly(4-vinylpyridine) chains, which were
      positively charged at acidic pH values. The functionalization reaction was
      checked by measuring the current-voltage curves prior to and after the
      chemisorption of polymer chains. The experimental nanopore characterization
      included the effects of temperature, adsorption of chloride ions, electrolyte
      concentration, and pH of the external solutions. The results obtained are further
      explained in terms of a theoretical continuous model. The combination of well
      established chemical procedures (thiol and self-assembled monolayer formation
      chemistry, electroless plating, ion track etching) and physical models (two
      region pore and Nernst-Planck equations) permits the obtainment of a new nanopore
      with high current rectification ratios. The single pore could be scaled up to
      multipore membranes of potential interest for pH sensing and chemical actuators. 

PMID- 25051047
TI  - Age-related different relationships between ectopic adipose tissues and measures
      of central obesity in sedentary subjects.
AB  - Accumulation of fat at ectopic sites has been gaining attention as pivotal
      contributor of insulin resistance, metabolic syndrome and related cardiovascular
      complications. Intermuscular adipose tissue (IMAT), located between skeletal
      muscle bundles and beneath muscle fascia, has been linked to physical inactivity,
      ageing and body mass index, but little is known about its relationship with the
      other AT compartments, in particular with increasing age. To address this issue,
      erector spinae IMAT, epicardial (EAT), intraabdominal (IAAT) and abdominal
      subcutaneous adipose tissue (SAT) were simultaneously measured by Magnetic
      Resonance Imaging (MRI) and related to waist circumference measurements and age
      in 32 sedentary subjects without cardiovascular disease (18 men; 14 women; mean
      age 48.5 +/- 14 years). Fasting glucose, triglycerides and HDL-cholesterol were
      also assessed. We observed that, after dividing individuals according to age (<=
      or > 50 years), IMAT and EAT depots were significantly more expanded in older
      subjects (63.2 +/- 8.3 years) than in the younger ones (38.4 +/- 5.2 years) (p <
      0.001). Overall, both IMAT and EAT showed stronger positive associations with
      increasing age (beta = 0.63 and 0.67, respectively, p < 0.001 for both) than with
      waist circumference (beta = 0.55 and 0.49, respectively, p < 0.01 for both) after
      adjusting for gender. In addition, the gender-adjusted associations of IMAT and
      EAT with waist circumference and IAAT were significant in individuals <= 50 years
      only (p<0.05 for all) and not in the older ones. In contrast, no age-related
      differences were seen in the relationships of IAAT and SAT with waist
      circumference. Finally, serum triglycerides levels turned out not to be
      independently related with ectopic IMAT and EAT. In conclusion, the expansion of
      IMAT and EAT in sedentary subjects is more strongly related to age than waist
      circumference, and a positive association of these ectopic depots with waist
      circumference and IAAT amount can be postulated in younger individuals only.

PMID- 25051048
TI  - HSP60 is involved in the neuroprotective effects of naloxone.
AB  - Heat shock protein (HSP)60 is primarily a mitochondrial protein. Previous
      experiments have found that changes in the location of intracellular HSP60 have
      been associated with apoptosis. Extracellular HSP60 mediates apoptosis via its
      ligand, Toll-like receptor (TLR)-4. TLR-4 is an important factor expressed on
      microglia, with a central role in generating neuroimmune responses in the
      pathogenesis of neurodegenerative disorders. Naloxone is a highly effective
      nonselective opioid receptor antagonist, and has been reported to be
      pharmacologically beneficial for the treatment of brain diseases through
      inhibiting microglia activation. However, the mechanisms underlying these
      beneficial effects of naloxone remain poorly understood. The present study aimed
      to investigate the role of HSP60 in the neuroprotective effects of naloxone on
      the production of proinflammatory mediators in lipopolysaccharide (LPS)
      stimulated BV2 murine microglial cells and the possible signaling pathways
      involved. The results demonstrated that naloxone significantly inhibited the
      expression and release of HSP60 in BV2 cells. The expression levels of heat shock
      factor (HSF)-1 were upregulated in LPS-activated BV2 cells, which indicated that
      the increased expression of HSP60 was driven by HSF-1 activation. However,
      increased HSF-1 levels may be downregulated by naloxone. The levels of TLR-4 were
      elevated in activated BV2 cells, and then inhibited by naloxone. Activation of
      TLR-4 is characterized by activation of nuclear factor-kappaB (NF-kappaB)
      followed by the production of various proinflammatory and neurotoxic factors.
      Data from the present study demonstrated that naloxone reduced the expression
      levels of NF-kappaB and its upstream protein caspase-3, and reduced the LPS
      induced production of nitric oxide, inducible nitric oxide synthase, tumor
      necrosis factor alpha, interleukin-1beta and interleukin-6 in BV2 microglia. In
      light of this data, it was concluded that naloxone may exert its neuroprotective
      and anti-inflammatory effects by inhibiting microglia activation through a HSP60
      TLR-4-NF-kappaB signaling pathway.

PMID- 25051049
TI  - Soluble Lutheran/basal cell adhesion molecule is detectable in plasma of
      hepatocellular carcinoma patients and modulates cellular interaction with laminin
      511 in vitro.
AB  - Lutheran (Lu), an immunoglobulin superfamily transmembrane receptor, is also
      known as basal cell adhesion molecule (B-CAM). Lu/B-CAM is a specific receptor
      for laminin alpha5, a subunit of laminin-511 (LM-511) that is a major component
      of basement membranes in various tissues. Our previous study showed that Lu/B-CAM
      was cleaved by MT1-MMP and released from cell surfaces. In this study we examined
      the soluble Lu/B-CAM in culture media and in plasma of mice bearing HuH-7
      hepatocellular carcinoma (HCC) cells and patients with HCC. Two HCC cell lines,
      HepG2 and HuH-7, released Lu/B-CAM into the culture media. Although Lu/B-CAM was
      cleaved by MT1-MMP in HuH-7 cells, HepG2 cells released Lu/B-CAM in a MMP
      independent manner. The concentration of Lu/B-CAM released into mouse plasma
      correlated with tumor size. Moreover the soluble Lu/B-CAM in plasma of HCC
      patients was significantly decreased after resection of the tumor.
      Immunohistochemical studies showed that although the expression of Lu/B-CAM was
      observed in most HCCs, MT1-MMP was not always expressed in tumor tissues,
      suggesting that a part of Lu/B-CAM in plasma of HCC patients was also released in
      a MMP-independent manner. In vitro studies showed that the soluble Lu/B-CAM
      released from HCC cells bound to LM-511. Moreover the soluble Lu/B-CAM influenced
      cell migration on LM-511. These results suggest that soluble Lu/B-CAM serves as
      not only a novel marker for HCC but also a modulator in tumor progression.

PMID- 25051050
TI  - Identification and expression analysis of the zebrafish orthologues of the
      mammalian MAP1LC3 gene family.
AB  - Autophagy is the principle pathway within cells involved in clearing damaged
      proteins and organelles. Therefore autophagy is necessary to maintain the
      turnover balance of peptides and homoeostasis. Autophagy occurs at basal levels
      under normal conditions but can be upregulated by chemical inducers or stress
      conditions. The zebrafish (Danio rerio) serves as a versatile tool to understand
      the functions of genes implicated in autophagy. We report the identification of
      the zebrafish orthologues of mammalian genes MAP1LC3A (map1lc3a) and MAP1LC3B
      (map1lc3b) by phylogenetic and conserved synteny analysis and we examine their
      expression during embryonic development. The zebrafish map1lc3a and map1lc3b
      genes both show maternally contributed transcripts in early embryogenesis.
      However, levels of map1lc3a transcript steadily increase until at least 120h post
      fertilisation while the levels of map1lc3b show a more variable pattern across
      developmental time. We have also validated the LC3I ratio/LC3I immunoblot
      autophagy assay in the presence of chloroquine (a lysosomal proteolysis
      inhibitor). We found that the LC3II/LC3I ratio is significantly increased in the
      presence of sodium azide with chloroquine supporting that hypoxia induces
      autophagy in zebrafish. This was supported by our qPCR assay that showed
      increased map1lc3a transcript levels in the presence of sodium azide. In
      contrast, levels of map1lc3b transcripts were reduced in the presence of
      rapamycin but the decrease in the presence of sodium azide did not reach
      statistical significance. Our study supports the use of zebrafish for analysing
      the interplay between hypoxia, development and autophagy.

PMID- 25051052
TI  - Association between obesity and prescribed medication use in England.
AB  - We investigate the association between obesity and use of prescribed medications
      in England. Data were taken from fourteen rounds of the Health Survey for England
      (1999-2012), which has measures of current prescribed medication use based on
      therapeutic classifications in the British National Formulary, and nurse-measured
      height and weight. We find that obesity has a statistically significant and
      positive association with use of a range of medicines for managing diseases
      associated with obesity. The mean probability of using any type of medication is
      0.40 in those of normal weight, 0.44 in the overweight, 0.52 in obesity class I
      and 0.60 in obesity class II/III. Significant positive associations were found
      between obesity and the use of medication for diseases of the cardiovascular
      system, gastrointestinal system, respiratory system, and central nervous system,
      as well as for infections, endocrine system disorders, gynaecological/urinary
      disorders and musculoskeletal and joint disorders. Use of anti-obesity medication
      is low, even among those with class II/III obesity. 

PMID- 25051051
TI  - 19F NMR fingerprints: identification of neutral organic compounds in a molecular
      container.
AB  - Improved methods for quickly identifying neutral organic compounds and
      differentiation of analytes with similar chemical structures are widely needed.
      We report a new approach to effectively "fingerprint" neutral organic molecules
      by using (19)F NMR and molecular containers. The encapsulation of analytes
      induces characteristic up- or downfield shifts of (19)F resonances that can be
      used as multidimensional parameters to fingerprint each analyte. The strategy can
      be achieved either with an array of fluorinated receptors or by incorporating
      multiple nonequivalent fluorine atoms in a single receptor. Spatial proximity of
      the analyte to the (19)F is important to induce the most pronounced NMR shifts
      and is crucial in the differentiation of analytes with similar structures. This
      new scheme allows for the precise and simultaneous identification of multiple
      analytes in a complex mixture. 

PMID- 25051053
TI  - Methane destruction efficiency of natural gas flares associated with shale
      formation wells.
AB  - Flaring to dispose of natural gas has increased in the United States and is
      typically assumed to be 98% efficient, accounting for both incomplete combustion
      and venting during unintentional flame termination. However, no in situ
      measurements of flare emissions have been reported. We used an aircraft platform
      to sample 10 flares in North Dakota and 1 flare in Pennsylvania, measuring CO2,
      CH4, and meteorological data. Destruction removal efficiency (DRE) was calculated
      by assuming a flare natural gas input composition of 60-100% CH4. In all cases
      flares were >99.80 efficient at the 25% quartile. Crosswinds up to 15 m/s were
      observed, but did not significantly adversely affect efficiency. During analysis
      unidentified peaks of CH4, most likely from unknown venting practices, appeared
      much larger in magnitude than emissions from flaring practices. Our analysis
      suggests 98% efficiency for nonsputtering flares is a conservative estimate for
      incomplete combustion and that the unidentified venting is a greater contributor
      to CH4 emissions. 

PMID- 25051055
TI  - Nitrosylation mechanisms of Mycobacterium tuberculosis and Campylobacter jejuni
      truncated hemoglobins N, O, and P.
AB  - Truncated hemoglobins (trHbs) are widely distributed in bacteria and plants and
      have been found in some unicellular eukaryotes. Phylogenetic analysis based on
      protein sequences shows that trHbs branch into three groups, designated N (or I),
      O (or II), and P (or III). Most trHbs are involved in the O2/NO chemistry and/or
      oxidation/reduction function, permitting the survival of the microorganism in the
      host. Here, a detailed comparative analysis of kinetics and/or thermodynamics of
      (i) ferrous Mycobacterium tuberculosis trHbs N and O (Mt-trHbN and Mt-trHbO,
      respectively), and Campylobacter jejuni trHb (Cj-trHbP) nitrosylation, (ii)
      nitrite-mediated nitrosylation of ferrous Mt-trHbN, Mt-trHbO, and Cj-trHbP, and
      (iii) NO-based reductive nitrosylation of ferric Mt-trHbN, Mt-trHbO, and Cj-trHbP
      is reported. Ferrous and ferric Mt-trHbN and Cj-trHbP display a very high
      reactivity towards NO; however, the conversion of nitrite to NO is facilitated
      primarily by ferrous Mt-trHbN. Values of kinetic and/or thermodynamic parameters
      reflect specific trHb structural features, such as the ligand diffusion pathways
      to/from the heme, the heme distal pocket structure and polarity, and the ligand
      stabilization mechanisms. In particular, the high reactivity of Mt-trHbN and Cj
      trHbP reflects the great ligand accessibility to the heme center by two protein
      matrix tunnels and the E7-path, respectively, and the penta-coordination of the
      heme-Fe atom. In contrast, the heme-Fe atom of Mt-trHbO the ligand accessibility
      to the heme center of Mt-trHbO needs large conformational readjustments, thus
      limiting the heme-based reactivity. These results agree with different roles of
      Mt-trHbN, Mt-trHbO, and Cj-trHbP in vivo.

PMID- 25051056
TI  - Effect of losartan on serum uric acid in hypertension treated with a diuretic:
      the COMFORT study.
AB  - It has been shown that losartan, an angiotensin II receptor blocker (ARB),
      reduces serum uric acid levels. However, the effects of losartan on serum uric
      acid levels in the patients treated with a thiazide diuretic have not been fully
      elucidated. We have investigated the effects of losartan compared with other ARBs
      on blood variables and blood pressure control in hypertensive patients treated
      with a thiazide diuretic using data from the COMFORT study. The present analysis
      included a total of 118 hypertensive subjects on combination treatment with ARBs
      except for losartan and a diuretic who were randomly assigned to a daily regimen
      of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or to
      continuation of two pills, an ARB except for losartan and a diuretic. Blood
      pressures were evaluated at 1, 3, and 6 months after randomization and changes in
      blood variables including serum uric acid were evaluated during 6 months
      treatment period. Mean follow-up blood pressure levels were not different between
      the combination pill (losartan treatment) group and the control (ARBs except for
      losartan) group. On the other hand, serum uric acid significantly decreased in
      the combination pill group compared with the control group (-0.44 versus + 0.10
      mg/dl; p = 0.01), although hematocrit, serum creatinine, sodium and potassium
      were not different between the groups. These results suggest that the treatment
      regimen switched from a combination therapy of ARBs except for losartan and a
      diuretic to a combination pill (losartan/ hydrochlorothiazide) decreases serum
      uric acid without affecting blood pressure control.

PMID- 25051058
TI  - Is colon capsule endoscopy ready for prime time?

PMID- 25051057
TI  - Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of
      neuronal development in trans-placental exposure to bisphenol A.
AB  - BACKGROUND: Bisphenol A (BPA) is a ubiquitous endocrine disrupting chemical in
      our daily life, and its health effect in response to prenatal exposure is still
      controversial. Early-life BPA exposure may impact brain development and
      contribute to childhood neurological disorders. The aim of the present study was
      to investigate molecular target genes of neuronal development in trans-placental
      exposure to BPA. METHODOLOGY: A meta-analysis of three public microarray datasets
      was performed to screen for differentially expressed genes (DEGs) in exposure to
      BPA. The candidate genes of neuronal development were identified from gene
      ontology analysis in a reconstructed neuronal sub-network, and their gene
      expressions were determined using real-time PCR in 20 umbilical cord blood
      samples dichotomized into high and low BPA level groups upon the median 16.8 nM.
      PRINCIPAL FINDINGS: Among 36 neuronal transcripts sorted from DAVID ontology
      clusters of 457 DEGs using the analysis of Bioconductor limma package, we found
      two neuronal genes, sex determining region Y-box 2 (Sox2) and paired box 6
      (Pax6), had preferentially down-regulated expression (Bonferroni correction p
      value <10(-4) and log2-transformed fold change <=-1.2) in response to BPA
      exposure. Fetal cord blood samples had the obviously attenuated gene expression
      of Sox2 and Pax6 in high BPA group referred to low BPA group. Visualized gene
      network of Cytoscape analysis showed that Sox2 and Pax6 which were contributed to
      neural precursor cell proliferation and neuronal differentiation might be down
      regulated through sonic hedgehog (Shh), vascular endothelial growth factor A
      (VEGFA) and Notch signaling. CONCLUSIONS: These results indicated that trans
      placental BPA exposure down-regulated gene expression of Sox2 and Pax6
      potentially underlying the adverse effect on childhood neuronal development.

PMID- 25051059
TI  - Radiofrequency ablation for Barrett's esophagus with low-grade dysplasia: a
      hammer looking for a nail.

PMID- 25051054
TI  - Repair of oxidative DNA base damage in the host genome influences the HIV
      integration site sequence preference.
AB  - Host base excision repair (BER) proteins that repair oxidative damage enhance HIV
      infection. These proteins include the oxidative DNA damage glycosylases 8-oxo
      guanine DNA glycosylase (OGG1) and mutY homolog (MYH) as well as DNA polymerase
      beta (Polbeta). While deletion of oxidative BER genes leads to decreased HIV
      infection and integration efficiency, the mechanism remains unknown. One
      hypothesis is that BER proteins repair the DNA gapped integration intermediate.
      An alternative hypothesis considers that the most common oxidative DNA base
      damages occur on guanines. The subtle consensus sequence preference at HIV
      integration sites includes multiple G:C base pairs surrounding the points of
      joining. These observations suggest a role for oxidative BER during integration
      targeting at the nucleotide level. We examined the hypothesis that BER repairs a
      gapped integration intermediate by measuring HIV infection efficiency in Polbeta
      null cell lines complemented with active site point mutants of Polbeta. A DNA
      synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection
      efficiency to wild type levels; this suggested Polbeta DNA synthesis activity is
      not necessary while 5'dRP lyase activity is required for efficient HIV infection.
      An alternate hypothesis that BER events in the host genome influence HIV
      integration site selection was examined by sequencing integration sites in OGG1
      and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases
      the chromatin elements of HIV integration site selection remain the same as in
      wild type cells. However, the HIV integration site sequence preference at G:C
      base pairs is altered at several positions in OGG1 and MYH null cells.
      Inefficient HIV infection in the absence of oxidative BER proteins does not
      appear related to repair of the gapped integration intermediate; instead
      oxidative damage repair may participate in HIV integration site preference at the
      sequence level.

PMID- 25051060
TI  - Results of a standardized endoscopic approach to resection of polyps >20 mm.

PMID- 25051061
TI  - A simple and reliable method for determining the delamination degree of nitrate
      and glycine intercalated LDHs in formamide.
AB  - We demonstrated that analyzing the formed gels containing exfoliated nitrate or
      glycine intercalated layered double hydroxide (LDH) nanosheets in formamide using
      X-ray diffraction is a simple and reliable method for determining the
      delamination degree of LDHs in formamide, which shows many advantages compared to
      the common characterization technologies. 

PMID- 25051063
TI  - Disaggregation ability of different chelating molecules on copper ion-triggered
      amyloid fibers.
AB  - Dysfunctional interaction of amyloid-beta (Abeta) with excess metal ions is
      proved to be related to the etiology of Alzheimer's disease (AD). Using metal
      binding compounds to reverse metal-triggered Abeta aggregation has become one of
      the potential therapies for AD. In this study, the ability of a carboxylic acid
      gemini surfactant (SDUC), a widely used metal chelator (EDTA), and an antifungal
      drug clioquinol (CQ) in reversing the Cu(2+)-triggered Abeta(1-40) fibers have
      been systematically studied by using turbidity essay, BCA essay, atomic force
      microscopy, transmission electron microscopy, and isothermal titration
      microcalorimetry. The results show that the binding affinity of Cu(2+) with CQ,
      SDUC, and EDTA is in the order of CQ > EDTA > SDUC, while the disaggregation
      ability to Cu(2+)-triggered Abeta(1-40) fibers is in the order of CQ > SDUC >
      EDTA. Therefore, the disaggregation ability of chelators to the Abeta(1-40)
      fibers does not only depend on the binding affinity of the chelators with Cu(2+).
      Strong self-assembly ability of SDUC and pi-pi interaction of the conjugate group
      of CQ also contributes toward the disaggregation of the Cu(2+)-triggered Abeta(1
      40) fibers and result in the formation of mixed small aggregates. 

PMID- 25051062
TI  - The association of uremic toxins and inflammation in hemodialysis patients.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of mortality in
      hemodialysis patients and is associated with chronic inflammation. Elevation of
      uremic toxins, particular protein-bound uremic toxins, is a possible cause of
      hyper-inflammation in hemodialysis patients. But the association between uremic
      toxins and inflammatory markers in hemodialysis is still unclear. METHODS: We
      conducted a cross-sectional study to evaluate the association of the serum uremic
      toxins and inflammatory markers in hemodialysis patients. RESULTS: The uremic
      toxins were not associated with inflammatory markers--including high sensitivity
      C-reactive protein, IL(Interleukin) -1beta, IL-6, tumor necrosis factor-alpha. In
      multiple linear regression, serum levels of total p-cresol sulfate (PCS) were
      independently significantly associated with serum total indoxyl sulfate (IS)
      (standardized coefficient: 0.274, p<0.001), and co-morbidity of diabetes mellitus
      (DM) (standardized coefficient: 0.342, p<0.001) and coronary artery disease (CAD)
      (standardized coefficient: 0.128, p = 0.043). The serum total PCS levels in
      hemodialysis with co-morbidity of DM and CAD were significantly higher than those
      without co-morbidity of DM and CAD (34.10+/-23.44 vs. 16.36+/-13.06 mg/L,
      p<0.001). Serum levels of total IS was independently significantly associated
      with serum creatinine (standardized coefficient: 0.285, p<0.001), total PCS
      (standardized coefficient: 0.239, p = 0.001), and synthetic membrane dialysis
      (standardized coefficient: 0.139, p = 0.046). CONCLUSION: The study showed that
      serum levels of total PCS and IS were not associated with pro-inflammatory
      markers in hemodialysis patients. Besides, serum levels of total PCS were
      independently positively significantly associated with co-morbidity of CAD and
      DM.

PMID- 25051064
TI  - Enhanced rosmarinic acid biosynthesis in Solenostemon scutellarioides culture: a
      precursor-feeding strategy.
AB  - The aim of this study was to employ precursor-feeding strategy for the improved
      production of rosmarinic acid (RA) in Solenostemon scutellarioides in vitro. The
      cultures were fed with precursors, namely l-phenylalanine (Phe), l-tyrosine (Tyr)
      and cucumber juice (CJ), at different concentrations. Phe (100 mg L(-1)) and Tyr
      (400 mg L(-1)) caused ~1.5- and 2.1-fold increase in RA accumulation within 48 h.
      CJ (50 mg L(-1)) feeding displayed highest RA content (~1.6-fold) in 72 h. In
      this study, we focused on the function of individual precursor on key enzymes
      involved in RA biosynthesis. The phenylalanine ammonia lyase activity was
      significantly upregulated after Phe (100 mg L(-1)) feeding, while tyrosine
      aminotransferase and hydroxyphenylpyruvate reductase activities were improved
      with Tyr (400 mg L(-1)) treatment. However, rosmarinic acid synthase activity was
      significantly enhanced by all three precursors. In synergy study, Phe (100 mg L(
      1)) + Tyr (400 mg L(-1)) could enhance (~3.1-fold) RA biosynthesis within 48 h.

PMID- 25051066
TI  - The dynamics of a metapopulation: changes in life-history traits in resident
      herring that co-occur with oceanic herring during spawning.
AB  - Different populations of Atlantic herring are regarded as forming a
      metapopulation, but we know little about the dynamics of the connectivity and
      degree of interbreeding between the populations. Based on data from three periods
      between 1962 and 2011, we identified the presence of two components of herring in
      a small semi-enclosed coastal marine ecosystem based on different somatic growth
      patterns and mean vertebrae sum (VS). The two components were interpreted as
      belonging to a resident herring population and the migratory, oceanic Norwegian
      spring spawning (NSS) herring population, and they co-occurred during spawning.
      In the 1960s, resident herring characterized by slow growth and low VS co
      occurred with rapid growth, high VS oceanic NSS herring. Similar slow-growing
      resident and rapid-growing NSS herring were found in the 1970-80s, but both
      populations now had low VS suggesting similar origins. Finally, in the 2000s both
      populations showed rapid growth. The changes coincided with the NSS herring going
      from a state of high abundance and oceanic distribution to a collapse in the late
      1960s that resulted in a coastal distribution closer to resident herring
      populations, before full recovery and resumption of the migratory, oceanic
      pattern in the 1990s. During all three periods, NSS herring were only present in
      the local system up to an age of about five years, but the synchronous spawning
      of the populations supports mixed spawning and interbreeding. During the
      investigation period both longevity, length at age (growth) and length-at-first
      maturity increased markedly for the resident herring, which then became more
      similar to the NSS herring. Genetic and/or cultural factors are believed to be
      the main causes of the observed changes in life history traits, although some
      effect of changes in environmental factors cannot be excluded. Our study suggests
      that relationships among populations in a metapopulation can be highly dynamic. 

PMID- 25051067
TI  - Dynamic bowtie filter for cone-beam/multi-slice CT.
AB  - A pre-patient attenuator ("bowtie filter" or "bowtie") is used to modulate an
      incoming x-ray beam as a function of the angle of the x-ray with respect to a
      patient to balance the photon flux on a detector array. While the current dynamic
      bowtie design is focused on fan-beam geometry, in this study we propose a
      methodology for dynamic bowtie design in multi-slice/cone-beam geometry. The
      proposed 3D dynamic bowtie is an extension of the 2D prior art. The 3D bowtie
      consists of a highly attenuating bowtie (HB) filled in with heavy liquid and a
      weakly attenuating bowtie (WB) immersed in the liquid of the HB. The HB targets a
      balanced flux distribution on a detector array when no object is in the field of
      view (FOV). The WB compensates for an object in the FOV, and hence is a scaled
      down version of the object. The WB is rotated and translated in synchrony with
      the source rotation and patient translation so that the overall flux balance is
      maintained on the detector array. First, the mathematical models of different
      scanning modes are established for an elliptical water phantom. Then, a numerical
      simulation study is performed to compare the performance of the scanning modes in
      the cases of the water phantom and a patient cross-section without any bowtie and
      with a dynamic bowtie. The dynamic bowtie can equalize the numbers of detected
      photons in the case of the water phantom. In practical cases, the dynamic bowtie
      can effectively reduce the dynamic range of detected signals inside the FOV.
      Furthermore, the WB can be individualized using a 3D printing technique as the
      gold standard. We have extended the dynamic bowtie concept from 2D to 3D by using
      highly attenuating liquid and moving a scale-reduced negative copy of an object
      being scanned. Our methodology can be applied to reduce radiation dose and
      facilitate photon-counting detection. 

PMID- 25051068
TI  - Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit
      locus are associated with COPD risk based on meta-analyses.
AB  - BACKGROUND: Several single nucleotide polymorphisms (SNPs) in an alpha-neuronal
      nicotinic acetylcholine receptor subunit (CHRNA3/5) were identified to be
      associated with chronic obstructive pulmonary disease (COPD) in a study based on
      a Norwegian population. However, results from subsequent studies have been
      controversial, particularly in studies recruiting Asians. In the present study,
      we conducted a comprehensive search and meta-analyses to identify susceptibility
      SNPs for COPD in the CHRNA3/5 locus. METHODS: A comprehensive literature search
      was conducted to find studies that have reported an association between SNPs in
      the CHRNA3/5 locus and COPD risk. Pooled odds ratios (ORs) with 95% confidence
      intervals (CIs) for each SNP were calculated with the major allele or genotype as
      the reference group. The influence of individual studies on pooled measures was
      assessed, in addition to publication bias. RESULTS: A total of 12 articles with
      14 eligible studies were included in this analysis. Association between 4 SNPs in
      the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191,
      rs6495309, and rs16969968. Significant associations between the 4 SNPs and COPD
      were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10-1.18; rs8034191:
      OR = 1.29, 95%CI = 1.18-1.41; rs6495309: OR = 1.26, 95%CI = 1.09-1.45;
      rs16969968: OR = 1.27, 95%CI = 1.17-1.39) and genotype models. Subgroup analysis
      conducted for rs1051730 showed a significant association between this SNP and
      COPD risk in non-Asians (OR = 1.14, 95%CI = 1.10-1.18), but not Asians (OR =
      1.23, 95%CI = 0.91-1.67). Rs1051730 and rs6495309 were also significantly
      associated with COPD after adjusting for multiple variables, including age and
      smoking status. CONCLUSION: Our results indicate that 4 SNPs in the CHRNA3/5
      locus are associated with COPD risk. Rs1051730 was particularly associated with
      COPD in non-Asians, but its role in Asians still needs to be verified. Additional
      studies will be necessary to assess the effect of rs6495309 on COPD. Although
      rs1051730 and rs6495309 were shown to be independent risk factors for COPD,
      validation studies should be performed.

PMID- 25051070
TI  - A 13-question approach to resolving serological discrepancies in the transfusion
      medicine laboratory.
AB  - Laboratory professionals, consultants, and treating physicians may encounter
      discrepancies in serological testing results for numerous reasons; identifying
      the reason(s) for the presence of an unexpected antibody or antigen can be
      challenging. A question-based approach can be useful in identifying the
      underlying cause of the discrepancy. We describe a new approach to serological
      problems in a transfusion-service laboratory. The approach we outline herein is
      targeted towards a general transfusion medicine service, rather than a center
      that offers complex antibody investigations using specialized techniques. This
      question-based problem-solving approach considers patient factors including
      diagnosis, transfusion history, previous pregnancies, and medication history,
      along with serological test results: ABO and Rh groups, direct and indirect
      antiglobulin tests, reacting temperature of the antibody, effect of enzyme
      treatment of cells, strength of reactivity, and antibody reactivity with
      umbilical cord cells. We also demonstrate the usefulness of this approach through
      a case scenario. 

PMID- 25051069
TI  - Codon-by-codon modulation of translational speed and accuracy via mRNA folding.
AB  - Rapid cell growth demands fast protein translational elongation to alleviate
      ribosome shortage. However, speedy elongation undermines translational accuracy
      because of a mechanistic tradeoff. Here we provide genomic evidence in budding
      yeast and mouse embryonic stem cells that the efficiency-accuracy conflict is
      alleviated by slowing down the elongation at structurally or functionally
      important residues to ensure their translational accuracies while sacrificing the
      accuracy for speed at other residues. Our computational analysis in yeast with
      codon resolution suggests that mRNA secondary structures serve as elongation
      brakes to control the speed and hence the fidelity of protein translation. The
      position-specific effect of mRNA folding on translational accuracy is further
      demonstrated experimentally by swapping synonymous codons in a yeast transgene.
      Our findings explain why highly expressed genes tend to have strong mRNA folding,
      slow translational elongation, and conserved protein sequences. The exquisite
      codon-by-codon translational modulation uncovered here is a testament to the
      power of natural selection in mitigating efficiency-accuracy conflicts, which are
      prevalent in biology. 

PMID- 25051071
TI  - QuantiFERON-TB Gold in-tube testing for tuberculosis in healthcare professionals.
AB  - OBJECTIVE: To assess the performance of the QuantiFERON-TB Gold in-tube (QFT-GIT)
      assay for tuberculosis (TB) screening using a convenience sample from among a
      population of healthcare provider (HCP) employees of a hospital. METHODS: For the
      individuals in our cohort, we reviewed occupational health records, including TB
      risk factors, and the results of QFT-GIT testing. We considered a QFT-GIT result
      of greater than 0.35 IU/mL to be positive; when we obtained a positive result
      from a specimen from a particular individual, we repeated testing on a fresh
      specimen from that individual. RESULTS: Of the 758 HCP employees whose specimens
      we screened, 439 had negative QFT-GIT results with negative TB risk factors and
      268 had a negative QFT-GIT result but had positive TB risk factors. QFT-GIT
      results were positive in 47 subjects. Of the positive participants, 12 had a mean
      TB antigen value (antigen minus nil stimulated concentrations [Ag-Nil]) of 0.61
      on initial testing and had a negative result on repeat testing, 22 had a TB Ag
      Nil of 1.19 on initial testing and had a positive result on repeat testing (P =
      .01). CONCLUSIONS: The QFT-GIT assay is useful for screening HCPs. However, false
      positive results occur, particularly in a borderline zone of less than 1 IU/ml.
      Re-evaluation by repeat testing of fresh specimens from the same individual
      should be considered in subjects whose specimens test within the low-level
      positive cutoff.

PMID- 25051072
TI  - Expression of IL4 (VNTR intron 3) and IL10 (-627) genes polymorphisms in
      childhood immune thrombocytopenic purpura.
AB  - OBJECTIVE: Immune thrombocytopenic purpura (ITP) is an acquired autoimmune
      disorder caused by the production of antiplatelet antibodies. These
      autoantibodies opsonize platelets for splenic clearance, resulting in low levels
      of circulating platelets. Interleukin 4 (IL4) and interleukin 10 (IL10) are
      important immunoregulatory cytokines mainly produced by macrophages, monocytes, T
      cells, B cells, and mast cells. Our study was aimed at detecting the frequency of
      IL4 (VNTR intron 3) and IL 10 (-627) gene polymorphisms in Egyptian ITP children
      as genetic markers for ITP risk and clarifying their possible role in the
      pathogenesis of ITP as well as their correlation with the clinical presentation
      and laboratory data. METHODS: IL4 (VNTR intron 3) and IL10 (-627) gene
      polymorphisms were studied in 70 ITP patients and 50 age- and sex-matched healthy
      controls using polymerase chain reaction-restriction fragment length polymorphism
      assay (PCR-RFLP). RESULTS: IL4 RP2 and IL10 A alleles were detected more
      frequently among ITP patients compared to controls. A statistically significant
      difference was observed in IL10 and IL4 gene polymorphism distribution between
      acute and chronic ITP patients, with higher A allele and RP2 allele among chronic
      ITP patients versus acute ITP patients. Combined polymorphisms of IL4 and IL10
      genes were associated with greater risk of ITP. CONCLUSION: IL4 and IL10 gene
      polymorphisms may contribute to susceptibility for ITP in children.

PMID- 25051073
TI  - Association of serum YKL-40 with the presence and severity of obstructive sleep
      apnea syndrome.
AB  - OBJECTIVE: This study examined the association of serum YKL-40 concentrations
      with the presence and severity of obstructive sleep apnea syndrome (OSAS).
      METHODS: A total of 156 patients with OSAS and 110 healthy subjects were enrolled
      in this study. RESULTS: OSAS patients had significantly higher serum YKL-40
      levels compared with healthy controls. Multivariable logistic regression analysis
      indicated that serum YKL-40 levels were an independent determinant of the
      presence of OSAS. Serum YKL-40 levels were significantly elevated in severe OSAS
      patients compared with mild and moderate OSAS patients. Spearman correlation
      analysis revealed that serum YKL-40 levels were correlated with the severity of
      OSAS. Simple linear regression analysis showed that the serum levels of YKL-40
      were correlated with body mass index (BMI), homeostasis model assessment of
      insulin resistance (HOMA-IR), C-reactive protein (CRP), and apnea-hypopnea index
      (AHI) in patients with OSAS. CONCLUSION: Elevated serum YKL-40 levels are
      associated with the presence and severity of OSAS.

PMID- 25051074
TI  - Measurement of HbA2 by capillary electrophoresis for diagnosing beta
      thalassemia/HbE disease in patients with low HbF.
AB  - OBJECTIVE: Capillary electrophoresis (CE) has the ability to detect hemoglobin
      (Hb) A2 in the presence of HbE. The aim of this study was to compare levels of
      HbA2 measured by CE between beta-thalassemia/HbE and homozygous HbE patients.
      METHODS: Molecular analysis for diagnosing of beta-thalassemia gene mutations and
      HbE was performed in 28 blood samples containing of HbE >75% and HbF levels
      varying from 5% to 15% quantified by high-performance liquid chromatography
      (HPLC). Levels of HbA2, HbE, and HbF were then measured using CE. RESULTS: Nine
      patients were diagnosed with beta-thalassemia/HbE disease and 19 with homozygous
      HbE. All patients with beta-thalassemia/HbE disease and only one patient (5%)
      with homozygous HbE had HbA2 higher than 6.0%. CONCLUSIONS: The analysis of HbA2
      level (>6.0%) by CE may be an alternative method for preliminary diagnosis of
      beta-thalassemia/HbE with uncertain beta-thalassemia/HbE disease and homozygous
      HbE.

PMID- 25051075
TI  - High rate of aminoglycoside resistance in CTX-M-15 producing Klebsiella
      pneumoniae isolates in Tehran, Iran.
AB  - OBJECTIVE: To determine the prevalence of extended-spectrum beta lactamases
      (ESBLs), the bla(CTX-M) genes, and aminoglycoside modifying enzymes genes in
      clinical isolates of Klebsiella pneumoniae (K. pneumoniae). METHODS: We collected
      200 nonduplicate clinical isolates of K. pneumoniae in hospitals in Tehran, Iran.
      We determined antibacterial susceptibility and confirmed ESBL production via the
      disk diffusion and minimum inhibitory concentration (MIC) methods. We identified
      bla(CTX-M) and aminoglycoside modifying enzymes genes via polymerase chain
      reaction (PCR). RESULTS: We detected 72 (36.0%) ESBL-positive K. pneumoniae, in
      which the bla(CTX-M-15) was dominant (62.5%). A total of 54.0% of isolates were
      resistant to at least 1 tested aminoglycoside; also, we detected aac(6')-Ib in
      42.5% of isolates and aac(3)-IIa in 35.1% of them. We observed a high rate of
      aminoglycoside-resistant genes (71.0%) among bla(CTX-M-15)-carrying isolates.
      CONCLUSION: We report that CTX-M-15 is the dominant type of CTX-M, which
      associates with entities that have high aminoglycoside resistance. Continuous
      surveillance and monitoring of this entity are needed because the codissemination
      of multiple drug-resistant genes with K. pneumoniae may become a serious
      therapeutic problem.

PMID- 25051076
TI  - Clinical and quality evaluation of red blood cell units collected via apheresis
      versus those obtained manually.
AB  - To evaluate the impact of collection procedure on the in vitro quality of red
      blood cells (RBC), we studied 30 units of apheresis-prepared RBC (ARBC) and 30
      units of manually collected RBC (MRBC). We performed assays on day 1 and day 21
      of the study, evaluating red cell mass volume (RCM); rate of hemolysis; pH, and
      levels of sodium, potassium, adenosine triphosphate (ATP), 2,3-diphosphoglycerate
      (2,3-DPG) and glucose. Eight patients with aplastic anemia received RBC
      transfusions of both components and their post-transfusion hematocrit (HCT)
      levels were compared. On day 21, we observed a significant drop of sodium and
      glucose levels in the ARBC group, compared with the MRBC group (P <.05). ARBC
      group demonstrated higher RCM that provided significantly higher HCT values to
      our group of anemic patients (P <.05). Hemolysis was significantly lower in the
      ARBC group, compared with the MRBC group (P <.05). At day 21, both groups had no
      detectable 2,3-DPG. Specimens from both groups retained ATP in sufficiently
      healthy amounts. The ARBC group demonstrated higher RCM and lower hemolysis
      levels compared with the MRBC group. 

PMID- 25051077
TI  - Large granules in the peripheral blood smear and bone marrow aspirate of a 3-year
      old male with lymphadenopathy and fever.
AB  - A 3-year-old male with oculocutaneous albinism presented with lymphadenopathy and
      fever. Serological testing revealed Epstein-Barr virus (EBV)-specific
      immunoglobulin M (IgM) and a diagnosis of infectious mononucleosis was made. A
      complete blood count and peripheral blood smear demonstrated mild anemia,
      thrombocytopenia, and neutropenia with leukocytes that contained large
      azurophilic and eosinophilic granules. Bone marrow examination demonstrated
      increased hemophagocytic histiocytes along with granulocytes that contained large
      eosinophilic granules. In addition to hemophagocytic lymphohistiocytosis,
      presumably due to acute EBV infection, the patient was diagnosed with Chediak
      Higashi syndrome based on the pathognomonic granules within peripheral leukocytes
      and precursors. The differential diagnosis of a young patient with oculocutaneous
      albinism presenting with an acute viral infection includes a relatively narrow
      range of genetic syndromes based solely on the history of albinism. This case
      demonstrates the application of clinical laboratory data to presumptively
      diagnose Chediak-Higashi syndrome in the midst of a presentation of
      hemophagocytic lymphohistiocytosis secondary to acute EBV infection. 

PMID- 25051078
TI  - Early diagnosis of intravascular large B-cell lymphoma: clues from routine blood
      smear morphologic findings.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is a mature B-cell neoplasm
      characterized by malignant lymphoid cells within the lumina of blood vessels and
      capillaries. Given its varied and nonspecific clinical manifestation, this
      aggressive disease is often not diagnosed until an advanced clinical stage or
      even at autopsy. This case highlights a patient presenting with autoimmune
      hemolytic anemia (AIHA) and fevers. Atypical circulating cells on a screening
      peripheral smear lead to flow cytometric studies highlighting an increase in
      large, light chain restricted CD20 positive cells. A diagnostic bone marrow
      biopsy was performed and trephine cores demonstrated predominantly
      intrasinusoidal lymphoma cells. In conjunction with additional immunophenotypic
      data, these studies strongly supported a diagnosis of IVLBCL. Judicious use of
      flow cytometry and morphology resulted in an early-stage diagnosis and likely
      contributed to the patient's current complete remission status following anti
      CD20 therapy. Differential diagnoses for this presentation are discussed in light
      of serologic, immunophenotypic, histologic, and cytogenetic findings. 

PMID- 25051079
TI  - Two case studies and a review of paroxysmal cold hemoglobinuria.
AB  - Paroxysmal cold hemoglobinuria (PCH) is an acquired hemolytic anemia caused by
      immunoglobulin G (IgG) antibodies that sensitize red blood cells (RBCs) at cold
      temperatures by fixing complement to the RBCs causing intravascular hemolysis on
      rewarming. PCH usually appears in young children as recurrent high fevers,
      chills, and passage of red-brown urine. The diagnostic test for PCH is the Donath
      Landsteiner test, an in vitro assay for biphasic hemolysis. Herein, we present 2
      cases of PCH that occurred within 12 months of each other. We quickly diagnosed
      the second case and treated the patient successfully, in part due to our
      recognition of its characteristics based on the first case. PCH is a hemolytic
      anemia for which there is a specific diagnostic test; the timely recognition of
      this entity by physicians and laboratory staff will allow prompt, supportive
      therapy and will raise the odds of quick resolution of hemolysis. 

PMID- 25051080
TI  - A case of false-positive test results in a pregnant woman of unknown HIV status
      at delivery.
AB  - We report a case of a false-positive HIV result in an apparently healthy pregnant
      woman. Since no prenatal HIV testing had been performed, we screened for HIV
      reactivity utilizing the Architect HIV-Ag/Ab Combo assay. Results obtained were
      inconsistent in that they were repeatedly HIV reactive on a single serum sample
      while nonreactive on a plasma sample. However, both sample types were nonreactive
      on the Advia Centaur HIV-1/O/2 and Oraquick assays. For further confirmation, an
      HIV-1 Western blot and viral load were performed; blot results were indeterminate
      while the viral load was undetectable. We concluded that the repeatedly reactive
      serum serology results were false-positive. While the cause of this false
      reactivity is not clear, most likely fibrin microclots in the serum sample
      interfered with the assay and thus accounted for the false positivity. Plasma may
      thus provide a more appropriate sample type when using the Architect assay,
      especially when testing pregnant women. 

PMID- 25051081
TI  - Improving appropriateness of blood utilization through prospective review of
      requests for blood products: the role of pathology residents as consultants.
AB  - OBJECTIVE: To evaluate the effectiveness of prospective review of orders for
      fresh-frozen plasma (FFP) and platelets in reducing blood-product use, and of the
      effectiveness of preparing pathology residents to serve as clinical consultants.
      DESIGN: At our 572-bed tertiary-care hospital, we developed guidelines for the
      use of blood products in collaboration with a variety of departments. For
      patients whose condition(s) met generally accepted criteria, we identified
      trigger points to allow for quick release by blood bank staff of blood products.
      For patients whose condition(s) did not meet the applicable criteria, the on-call
      pathology resident reviewed the medical record of that patient to determine
      whether there were any extenuating circumstances; consulted with the ordering
      physician and attending pathologist, as needed; and advised the house staff on
      appropriate use of blood products. We evaluated the change in use of blood
      products between the years 2009 and 2012 to assess the effectiveness of the
      program. RESULTS: We observed a decrease of 38.8% and 31.4% in the use of FFP and
      platelets, respectively (29.7% and 21.1%, respectively, when normalized for the
      number of discharges). If projected to the national level, this improvement would
      translate to an annual cost reduction of approximately $130 million. CONCLUSIONS:
      Prospective review of orders for blood products can significantly improve use of
      these products, thereby reducing risk to patients and avoiding unnecessary
      healthcare costs. The involvement of pathology residents in the prospective
      review process provides an excellent opportunity for their training as laboratory
      consultants.

PMID- 25051082
TI  - Evaluation of quality indicators in a laboratory supporting tertiary cancer care
      facilities in India.
AB  - OBJECTIVE: To collect and tabulate errors and nonconformities in the
      preanalytical, analytical, and postanalytical process phases in a diagnostic
      clinical laboratory that supports a super-specialty cancer center in India, and
      identify areas of potential improvement in patient services. METHODS: We
      collected data from our laboratory during a period of 24 months. Departments in
      the study included clinical biochemistry, hematology, clinical pathology,
      microbiology and serology, surgical pathology, and molecular pathology. We had
      initiated quality assessment based on international standards in our laboratory
      in 2010, with the aim of obtaining accreditation by national and international
      governing bodies. We followed the guidelines specified by International
      Organization for Standardization (ISO) 15189:2007 to identify noncompliant
      elements of our processes. RESULTS: Among a total of 144,030 specimens that our
      referral laboratory received during the 2-year period of our study, we uncovered
      an overall error rate for all 3 process phases of 1.23%; all of our error rates
      closely approximated the results from our peer institutions. Errors were most
      common in the preanalytical phase in both years of study; preanalytical- and
      postanalytical-phase errors constituted more than 90% of all errors. CONCLUSION:
      Further improvements are warranted in laboratory services and are contingent on
      adequate training and interdepartmental communication and cooperation.

PMID- 25051084
TI  - Developing a comprehensive faculty development program to promote
      interprofessional education, practice and research at a free-standing academic
      health science center.
AB  - There is an on-going transformation in health professions education to prepare
      students to function as competent members of an interprofessional team in order
      to increase patient safety and improve patient care. Various methods of health
      education and practice directed toward students have been implemented, yet
      descriptions of faculty development initiatives designed to advance
      interprofessional education and practice are scarce. This article describes a
      faculty development program at the Medical University of South Carolina, USA,
      based on the conceptual framework of adult transformational learning theory.
      Three components comprise the faculty development program: an institute,
      fellowship and teaching series. Evaluations of the three components indicate that
      the faculty development program aided in the sustainability of the university's
      interprofessional program, and built capacity for improvement and growth in
      interprofessional endeavors.

PMID- 25051085
TI  - Insight into team competence in medical, nursing and respiratory therapy
      students.
AB  - This study provides information for educators about levels of competence in teams
      comprised of medical, nursing and respiratory therapy students after receiving a
      simulation-based team-training (SBT) curriculum with and without an additional
      formalized 30-min team-training (TT) module. A two-group pre- and post-test
      research design was used to evaluate team competence with respect to leadership,
      roles and responsibilities, communication, situation awareness and resource
      utilization. All scenarios were digitally recorded and evaluated using the KidSIM
      Team Performance Scale by six experts from medicine, nursing and respiratory
      therapy. The lowest scores occurred for items that reflected situation awareness.
      All teams improved their aggregate scores from Time 1 to Time 2 (p < 0.05).
      Student teams in the intervention group achieved significantly higher performance
      scores at Time 1 (Cohen's d = 0.92, p < 0.001) and Time 2 (d = 0.61, p < 0.01).
      All student teams demonstrated significant improvement in their ability to work
      more effectively by Time 2. The results suggest that situational awareness is an
      advanced expectation for the undergraduate student team. The provision of a
      formalized TT module prior to engaging student teams in a simulation-based TT
      curriculum led to significantly higher performances at Time 1 and 2.

PMID- 25051083
TI  - Regulation of the innate immune response by fibronectin: synergism between the
      III-1 and EDA domains.
AB  - Fibronectin is a critical component of the extracellular matrix and alterations
      to its structure will influence cellular behavior. Matrix fibronectin is
      subjected to both mechanical and biochemical regulation. The Type III domains of
      fibronectin can be unfolded in response to increased cellular contractility,
      included or excluded from the molecule by alternative splicing mechanisms, or
      released from the matrix by proteolysis. Using Inflammatory Cytokine microarrays
      we found that the alternatively spliced fibronectin Type III domain, FnEDA, and
      the partially unfolded III-1 domain, FnIII-1c, induced the expression of a
      multitude of pro-inflammatory cytokines in human dermal fibroblasts, most notably
      CXCL1-3, IL-8 and TNF-alpha. FnIII-1c, a peptide representing an unfolded
      intermediate structure of the first Type III domain has been shown to initiate
      the toll-like receptor-4 (TLR4)-NFkappaB-dependent release of cytokines from
      human dermal fibroblasts (You, et al., J. Biol. Chem., 2010). Here we demonstrate
      that FnIII-1c and the alternatively spliced FnEDA domain induce a TLR4 dependent
      activation of p38 MAP kinase and its downstream effector, MAPKAP Kinase-2 (MK-2),
      to regulate cytokine expression in fibroblasts. RT-qPCR analysis indicated that
      the p38-MK-2 pathway regulates IL-8 mRNA stability. Interestingly, addition of
      FnIII-1c and FnEDA synergistically enhanced TLR4-dependent IL-8 release. These
      data indicate that Fn contains two Type III domains which can activate TLR
      signaling to induce an inflammatory response in fibroblasts. Furthermore, our
      data identifies the NF-kappaB and p38/MK2 signaling pathways as transducers of
      signals initiated in response to structural changes in fibronectin. 

PMID- 25051086
TI  - Enhancing patient-engaged teamwork in healthcare: an observational case study.
AB  - The purpose of this study was to describe how teamwork that effectively engaged
      patients and families, manifested itself in an acute rural care setting in order
      to inform the development of teamwork skills. One hundred and forty participants
      were included in the study representing providers, patients, family, hospital and
      clinical support personnel, education specialists and students. Using a modified
      grounded theory approach, and informed by activity theory, observational field
      notes and interview transcripts were analyzed. Through the analysis of 343 events
      of providers interacting with, or exchanging information about, patients, three
      patterns of teamwork emerged that facilitated patient-engaged care:
      uniprofessional, multiprofessional and interprofessional. The data indicated that
      providers navigated between these patterns, as well as others, throughout their
      workday. Providers should be skilled in applying the construct of situation
      awareness in order to adopt a pattern of teamwork that best facilitates patient
      engaged care. Interventions that can enhance teamwork should focus on: valuing
      the perspectives of others; developing relational competence and resilience;
      employing reflective learning and shared decision-making skills; and
      incorporating principles of change theory for both individuals and systems.

PMID- 25051087
TI  - Evaluation of medical and veterinary students' attitudes toward a one health
      interprofessional curricular exercise.
AB  - This study evaluates whether medical and veterinary students' attitudes toward
      "One Health" and interprofessional education changed after participating in a
      joint small group learning exercise focused on risk factors associated with
      zoonotic disease. A survey was distributed to third-year medical students (n =
      98) and second-year veterinary students (n = 140), each with a 95% response rate.
      Overall, 92% of veterinary students and 73% of medical students agreed or
      strongly agreed that "One Health" was relevant to their desired specialty.
      Students from both schools largely agreed that interprofessional education should
      be a goal of the curriculum for their school, and that interprofessional
      approaches strengthen their overall education. Students reported increased
      confidence in their communication skills and improved ability to contribute to
      One Health collaborative teams. This educational intervention, built around a
      patient case, focused on a variety of learning objectives including skills (such
      as communication), knowledge (of zoonotic toxoplasmosis) and attitudes (toward
      collaborative learning and practice). By sparking an interest in One Health
      during their early professional education, we sought to encourage a new
      generation of physicians and veterinarians to adopt a more collaborative spirit
      to their clinical practice, which will ultimately benefit human, animal and
      environmental health.

PMID- 25051088
TI  - Exploring issues of cost and value in professional and interprofessional
      education.

PMID- 25051089
TI  - Evidence of a shared purpose, critical reflection, innovation and leadership in
      interprofessional healthcare teams: a realist synthesis.
AB  - Realist synthesis is a theory-driven approach for evaluating complex
      interventions using empirical evidence, which seeks an explanatory analysis of
      who a complex intervention works for, how, why, and in what circumstances.
      Interprofessional teamworking in healthcare is one such complex intervention, as
      teams are influenced by social and organizational factors, which makes them
      highly variable and context dependent. This article concludes a series of four
      articles that report on a realist synthesis of interprofessional teamworking. The
      synthesis identified 13 mechanisms that are reported in the literature to be the
      underlying processes through which interprofessional teamworking produces its
      effects. This article explores four of these mechanisms: a shared purpose;
      critical reflection; innovation; and leadership. These mechanisms together
      explain how a team sets and maintains its focus and direction. This article
      highlights that whilst many assumptions are made within the healthcare literature
      about how these mechanisms operate within teams, these assumptions are not always
      founded upon strong empirical evidence. 

PMID- 25051090
TI  - Evidence of communication, influence and behavioural norms in interprofessional
      teams: a realist synthesis.
AB  - This article is the third in a series reporting the process and findings of a
      realist synthesis of interprofessional teamwork in health and social care. The
      synthesis articulated and tested four "mechanisms" (processes) of teamwork
      related to communication and found variable evidence to support them. Evidence
      was strongest for "efficient, open and equitable communication" and "tactical
      communication", but lacking for the shared responsibility element of the "shared
      responsibility and influence" mechanism. Little evidence was found to support or
      oppose the mechanism, "team behavioural norms", so its status as a mechanism of
      interprofessional teamwork is unclear. A striking finding for all the mechanisms
      was the dearth of information on how they affected patient clinical outcomes and
      experiences.

PMID- 25051091
TI  - Evidence of collaboration, pooling of resources, learning and role blurring in
      interprofessional healthcare teams: a realist synthesis.
AB  - Interprofessional teamwork has become an integral feature of healthcare delivery
      in a wide range of conditions and services in many countries. Many assumptions
      are made in healthcare literature and policy about how interprofessional teams
      function and about the outcomes of interprofessional teamwork. Realist synthesis
      is an approach to reviewing research evidence on complex interventions which
      seeks to explore these assumptions. It does this by unpacking the mechanisms of
      an intervention, exploring the contexts which trigger or deactivate them and
      connecting these contexts and mechanisms to their subsequent outcomes. This is
      the second in a series of four papers reporting a realist synthesis of
      interprofessional teamworking. The paper discusses four of the 13 mechanisms
      identified in the synthesis: collaboration and coordination; pooling of
      resources; individual learning; and role blurring. These mechanisms together
      capture the day-to-day functioning of teams and the dependence of that on
      members' understanding each others' skills and knowledge and learning from them.
      This synthesis found empirical evidence to support all four mechanisms, which
      tentatively suggests that collaboration, pooling, learning, and role blurring are
      all underlying processes of interprofessional teamwork. However, the supporting
      evidence for individual learning was relatively weak, therefore there may be
      assumptions made about learning within healthcare literature and policy that are
      not founded upon strong empirical evidence. There is a need for more robust
      research on individual learning to further understand its relationship with
      interprofessional teamworking in healthcare.

PMID- 25051092
TI  - Using realist synthesis to understand the mechanisms of interprofessional
      teamwork in health and social care.
AB  - Realist synthesis offers a novel and innovative way to interrogate the large
      literature on interprofessional teamwork in health and social care teams. This
      article introduces realist synthesis and its approach to identifying and testing
      the underpinning processes (or "mechanisms") that make an intervention work, the
      contexts that trigger those mechanisms and their subsequent outcomes. A realist
      synthesis of the evidence on interprofessional teamwork is described. Thirteen
      mechanisms were identified in the synthesis and findings for one mechanism,
      called "Support and value" are presented in this paper. The evidence for the
      other twelve mechanisms ("collaboration and coordination", "pooling of
      resources", "individual learning", "role blurring", "efficient, open and
      equitable communication", "tactical communication", "shared responsibility and
      influence", "team behavioural norms", "shared responsibility and influence",
      "critically reviewing performance and decisions", "generating and implementing
      new ideas" and "leadership") are reported in a further three papers in this
      series. The "support and value" mechanism referred to the ways in which team
      members supported one another, respected other's skills and abilities and valued
      each other's contributions. "Support and value" was present in some, but far from
      all, teams and a number of contexts that explained this variation were
      identified. The article concludes with a discussion of the challenges and
      benefits of undertaking this realist synthesis.

PMID- 25051093
TI  - Comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar
      disorder in a specialized mood disorders outpatient clinic.
AB  - BACKGROUND: Comorbidity between ADHD and Bipolar Disorder (BD) is associated with
      greater severity of BD. The current study aims at investigating, in a specialized
      mood disorders clinic, the percentage of comorbid ADHD-BD subjects and assessing
      the impact of ADHD on the severity of BD. METHODS: Out of 539 mood disorders
      subjects, the medical records of 138 BD subjects were scrutinized in terms of
      their clinical and demographic characteristics, and their scores at the Adult
      ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist were logged. Those
      positively scoring at the ASRS-v1.1 underwent clinical assessment by a senior
      psychiatrist specialized in ADHD. Comorbid ADHD-BD subjects were then compared
      with BD sufferers without ADHD. RESULTS: Sixty-three (45.65%) of the participants
      were screened positive at the ASRS-v1.1. 49 were clinically assessed for the
      presence of ADHD. Only 27 (55%) received a diagnosis of ADHD. Comorbid ADHD-BD
      subjects were found to be younger at the onset of BD, showed higher numbers of
      depressive episodes, more anxiety and substance use disorders, more borderline
      personality traits and greater cyclothymic temperament. Comorbid BD-ADHD subjects
      reported more childhood emotional abuse. LIMITATIONS: Some subjects were
      unreachable and thus not clinically assessed for ADHD. CONCLUSIONS: More than 20%
      of BD subjects were suffering from ADHD. The comorbidity of the two disorders was
      associated with worse outcomes, possibly resulting from stressful early-life
      events. More than 40% of the subjects who scored positively at the ASRS-v1.1 did
      not suffer from ADHD, which suggests that this scale should be used with caution
      in BD subjects.

PMID- 25051094
TI  - Prevalence and characterization of quinolone resistance mechanisms in commensal
      Escherichia coli isolated from slaughter animals in Poland, 2009-2012.
AB  - The background of quinolone resistance was characterized in ciprofloxacin
      resistant commensal Escherichia coli selected out of 3,551 isolates from
      slaughtered animals in Poland between 2009 and 2012. Plasmid-mediated
      determinants were suspected in 6.2% of the study group, ranging from 1.1% in
      cattle to 9.7% in turkeys. Polymerase chain reaction and sequencing identified up
      to four quinolone resistance-determining substitutions in gyrA (Ser83, Asp87) and
      parC (Ala56, Ser80). Plasmid-mediated mechanisms were identified as qnrS1 (or
      qnrS3, n=70, including six isolates with chromosomal mutations), qnrB19 (or
      qnrB10, n=19), and qnrB17 (n=1). All tested isolates were negative for qnrA,
      qnrC, qnrD, qepA, and aac(6')-Ib-cr. Still, there were several E. coli suspected
      for both plasmid- and chromosome-mediated resistance with unrevealed genetic
      background of the phenomenon. Since all tested isolates showed diverse XbaI-PFGE
      profiles, chromosome-encoded quinolone resistance does not result from the spread
      of a single resistant clone, however, it is rather due to antimicrobial pressure
      leading to the selection of random gyr and par mutants. It also favors the
      selection and spread of plasmids carrying predominant qnr genes, since the same
      determinants were found in Salmonella, isolated from similar sources. The
      identification of carrier plasmids and mitigation of their spread might be
      essential for sustainable quinolone usage in animal husbandry and efficient
      protection of human health. 

PMID- 25051095
TI  - Sequence-conserved and antibody-accessible sites in the V1V2 domain of HIV-1
      gp120 envelope protein.
AB  - The immune-correlates analysis of the RV144 trial suggested that epitopes
      targeted by protective antibodies (Abs) reside in the V1V2 domain of gp120. We
      mapped V1V2 positional sequence variation onto the conserved V1V2 structural fold
      and showed that while most of the solvent-accessible V1V2 amino acids vary
      between strains, there are two accessible molecular surface regions that are
      conserved and also naturally antigenic. These sites may contain epitopes targeted
      by broadly cross-reactive anti-V1V2 antibodies.

PMID- 25051096
TI  - Exploring versatile applications of cyclodextrins: an overview.
AB  - CONTEXT: Ever since the discovery of cyclodextrins, a family of cyclic
      oligosaccharides based on alpha (1 -> 4) linkage among glucopyranose subunits,
      these versatile supramolecular hosts have received tremendous attention for
      scientific explorations. Due to their property of forming host-guest type
      inclusion complex, cyclodextrins and their synthetic derivatives exhibit wide
      range of utilities in different areas viz. pharmaceuticals, drug delivery
      systems, cosmetics, food and nutrition, textile and chemical industry etc.
      OBJECTIVE: The purpose of this review is to highlight properties, advantages,
      recent studies and versatile benefits of cyclodextrins and to re-strengthen their
      prospective applications in novel directions for future research. METHODS: This
      article summarizes a variety of applications of cyclodextrins in various
      industrial products, technologies, analytical and chemical processes and recent
      industrial advancements by extensively literature search on various scientific
      databases, Google and websites of various associated pharmaceutical industries
      and patenting authorities across the world. RESULTS AND CONCLUSION: Due to
      possibility of multidimensional changes in physical and chemical properties of
      molecules upon inclusion complexation in cyclodextrins, these compounds are of
      great commercial interest and may offer solution to many of the scientific
      problems of the current world.

PMID- 25051097
TI  - Dualsteric muscarinic antagonists--orthosteric binding pose controls allosteric
      subtype selectivity.
AB  - Bivalent ligands of G protein-coupled receptors have been shown to simultaneously
      either bind to two adjacent receptors or to bridge different parts of one
      receptor protein. Recently, we found that bivalent agonists of muscarinic
      receptors can simultaneously occupy both the orthosteric transmitter binding site
      and the allosteric vestibule of the receptor protein. Such dualsteric agonists
      display a certain extent of subtype selectivity, generate pathway-specific
      signaling, and in addition may allow for designed partial agonism. Here, we want
      to extend the concept to bivalent antagonism. Using the phthal- and naphthalimide
      moieties, which bind to the allosteric, extracellular site, and atropine or
      scopolamine as orthosteric building blocks, both connected by a hexamethonium
      linker, we were able to prove a bitopic binding mode of antagonist hybrids for
      the first time. This is demonstrated by structure-activity relationships, site
      directed mutagenesis, molecular docking studies, and molecular dynamics
      simulations. Findings revealed that a difference in spatial orientation of the
      orthosteric tropane moiety translates into a divergent M2/M5 subtype selectivity
      of the corresponding bitopic hybrids. 

PMID- 25051098
TI  - Comparing the Cervista HPV HR test and Hybrid Capture 2 assay in a Dutch
      screening population: improved specificity of the Cervista HPV HR test by
      changing the cut-off.
AB  - The diagnostic performance of the widely-used Cervista HPV HR test was compared
      to the Hybrid Capture 2 (HC2) test in a Dutch population-based cervical cancer
      screening program. In 900 scrapings of women with normal cytomorphology,
      specificity was 90% (95%CI: 87.84-91.87) for the Cervista HPV HR test and 96%
      (95%CI: 94.76-97.37) for the HC2 test with 93% agreement between both tests
      (kappa = 0.5, p<0.001). The sensitivity for CIN2+ using 65 scrapings of women
      with histological-confirmed CIN2+ was 91% (95%CI: 80.97-96.51) for the Cervista
      HPV HR test and 92% (95%CI: 82.94-97.43) for the HC2 test with 95% agreement
      between both tests (kappa = 0.7, p<0.001). Fifty-seven of 60 HC2
      negative/Cervista positive cases tested HPV-negative with PCR-based HPV assays;
      of these cases 56% were defined as Cervista triple-positive with FOZ values in
      all 3 mixes higher than the second cut-off of 1.93 (as set by manufacturer). By
      setting this cut-off at 5.0, specificity improved significantly without affecting
      sensitivity. External validation of this new cut-off at 5.0 in triple-positive
      scrapings of women selected from the SHENCCASTII database revealed that 22/24
      histological normal cases now tested HPV-negative in the Cervista HPV HR test,
      while CIN2+ lesions remained HPV-positive. The intra-laboratory reproducibility
      of the Cervista HPV HR test (n = 510) showed a concordance of 92% and 93% for cut
      off 1.93 and 5.0 (kappa = 0.83 and kappa = 0.84, p<0.001) and inter-laboratory
      agreement of the Cervista HPV HR test was 90% and 93% for cut-off 1.93 and 5.0
      (kappa = 0.80 and kappa = 0.85, p<0.001). In conclusion, the specificity of the
      Cervista HPV HR test could be improved significantly by increasing the second cut
      off from 1.93 to 5.0, without affecting the sensitivity of the test in a
      population-based screening setting. 

PMID- 25051099
TI  - Mutual information and the fidelity of response of gene regulatory models.
AB  - We investigate cellular response to extracellular signals by using information
      theory techniques motivated by recent experiments. We present results for the
      steady state of the following gene regulatory models found in both prokaryotic
      and eukaryotic cells: a linear transcription-translation model and a positive or
      negative auto-regulatory model. We calculate both the information capacity and
      the mutual information exactly for simple models and approximately for the full
      model. We find that (1) small changes in mutual information can lead to
      potentially important changes in cellular response and (2) there are diminishing
      returns in the fidelity of response as the mutual information increases. We
      calculate the information capacity using Gillespie simulations of a model for the
      TNF-alpha-NF-kappaB network and find good agreement with the measured value for
      an experimental realization of this network. Our results provide a quantitative
      understanding of the differences in cellular response when comparing
      experimentally measured mutual information values of different gene regulatory
      models. Our calculations demonstrate that Gillespie simulations can be used to
      compute the mutual information of more complex gene regulatory models, providing
      a potentially useful tool in synthetic biology.

PMID- 25051102
TI  - SCN5A mutations and polymorphisms in patients with ventricular fibrillation
      during acute myocardial infarction.
AB  - Mutations in the SCN5A gene encoding the Nav1.5 channel alpha-subunit are known
      to be risk factors of arrhythmia, including Brugada Syndrome and Long QT syndrome
      subtype 3. The present study focused on the role of SCN5A variants in the
      development of ventricular fibrillation (VF) during acute myocardial infarction
      (AMI). Since VF during AMI is the major cause of sudden death in the Western
      world, SCN5A mutations represent genetic risk factors for sudden death. By exon
      re-sequencing, the entire coding region and flanking intron regions were
      sequenced in 46 AMI/VF+ patients. In total, nine single nucleotide variants were
      identified of which four represented common single nucleotide polymorphisms
      (SNPs; 87G>A, 1673A>G, IVS16-6C>T and 5457T>A). Only five rare variants were
      identified, each in only one patient. Only two of the rare variants represented
      missense mutations (3578G>A and 4786T>A). The common SNPs and the missense
      mutations were also genotyped using polymerase chain reaction methods in 79
      AMI/VF- patients and 480 healthy controls. The SNPs did not demonstrate
      significant differences in allele and genotype frequencies between the study
      groups. The 3578G>A mutation was identified in one out of the 480 controls,
      whereas the 4786T>A mutation was not present in AMI/VF- patients and controls. In
      conclusion, the majority of AMI/VF+ patients demonstrated a wild type sequence or
      common SNPs in SCN5A. Only two out of 46 (4.3%) AMI/VF+ patients revealed
      mutations that may be involved in Nav1.5 dysfunction and VF. However, this
      requires further functional validation.

PMID- 25051100
TI  - Correlation between coronary artery calcium score and aortic diameter in a high
      risk population of elderly male hypertensive patients.
AB  - BACKGROUND: Studies on the relationship between coronary artery calcium and
      aortic diameter are scarce. The aim of the current study was to evaluate the
      correlation between coronary artery calcium score (CACS) and maximal thoracic and
      abdominal aortic diameters in a population of elderly (>65 years) male
      hypertensive patients at high risk for coronary artery disease. PATIENTS AND
      METHODS: From June 2012 to April 2013, we prospectively enrolled 393 male
      hypertensive patients older than 65 years of age who had no history of aortic
      aneurysm. Coronary artery calcium and maximal diameters of the ascending thoracic
      aorta (ATAmax), descending thoracic aorta (DTAmax), and abdominal aorta (AAmax)
      were measured using noncontrast computed tomography imaging. Aortic diameters are
      indexed to body surface area (BSA). Participants were divided into five groups
      according to CACS (0, 1-10, 10-100, 100-400, and >400). RESULTS: The mean
      ATAmax/BSA, DTAmax/BSA, and AAmax/BSA were 22.0+/-2.7, 16.3+/-1.9, and 13.0+/-2.9
      mm, respectively. On multivariate analysis, ATAmax/BSA was associated
      independently with age, diabetes, and history of aortic valve replacement (all
      P<0.001). DTAmax/BSA was associated independently with age (P<0.001). However,
      there were no significant correlations between thoracic aorta diameter and CACS.
      In contrast, AAmax/BSA was associated independently with CACS as well as age and
      history of smoking (P=0.014, 0.003, and 0.019, respectively). Abdominal aortic
      aneurysm (>30 mm) was more prevalent in patients with a CACS of 400 or more
      compared with the others (14 vs. 3%, P<0.001). CONCLUSION: CACS was associated
      with increased abdominal aorta diameter, but not with thoracic aorta diameter.
      Therefore, screening for an abdominal aortic aneurysm is warranted in patients
      with a high risk of coronary artery disease and a high CACS. However, the
      necessity for thoracic aortic aneurysm screening is not clear in these patients.

PMID- 25051103
TI  - De novo congenital melanoma: analysis of 2 cases with array comparative genomic
      hybridization.
AB  - Congenital melanoma is extraordinarily rare, and 3 types have been described:
      transplacental metastases from the mother, de novo congenital melanoma, and
      melanoma occurring in association with a congenital melanocytic nevus. We
      describe 2 reports of array comparative genomic hybridization analysis of de novo
      congenital melanoma. The first patient was male, and the second was female; both
      had a scalp lesion present at birth, which grew quickly. The scalp mass from
      patient 1 showed a heterogeneous, anaplastic melanocytic neoplasm with large size
      and depth, high mitotic rate, ulceration, and necrosis. The scalp mass from
      patient 2 showed a broad melanocytic neoplasm with single cell and junctional
      nested proliferation at the dermal-epidermal junction and cellular, confluent
      aggregates of highly atypical melanocytes in the dermis with high mitotic rate.
      Patient 1 had lung and liver metastases detected by radiologic imaging and was
      treated with cisplatin, vinblastine, and dacarbazine but expired at the age of 5
      months. Patient 2 developed a metastasis to the right neck with similar
      histologic features, and pulmonary metastases were also detected by imaging.
      Patient 2 is currently alive at the age of 4 years. Array comparative genomic
      hybridization analysis of the first case revealed loss of chromosomes 3p26.3
      p21.31, 5p15.33-q23.1, 11q15.5-q13.2, 14 (complete deletion), and 15q11.1-q22.31.
      The second case displayed gains in chromosomes 1q21.1-q44, 2p25.3-p11.1, 2q11.1
      q37.3, 6p25.3-p11.1, 7p22.3-p11.2, 7q11.1-q36.3, 8p23.3-p11.1, 8q11.1-q24.3,
      9p24.3-p11.2, 9q12-q34.3, 11q13.2-q13.4, 13q11-q34, 18p11.32-p11.21, 19p13.3-p11,
      19q11-q13.43, 20p13-p11.1, and 20q11.21-q13.33. In both cases, the presence of
      multiple chromosomal aberrations corroborated the diagnosis of melanoma.

PMID- 25051104
TI  - Epidermolysis bullosa nevus in a patient with recessive dystrophic epidermolysis
      bullosa: a case report.
AB  - We present a case of a 6-year-old girl with recessive dystrophic epidermolysis
      bullosa (EB) who presented with a large pigmented lesion clinically concerning
      for melanoma. After histological examination and fluorescent in situ
      hybridization analysis, diagnosis of EB nevus was performed. EB nevi are benign
      melanocytic neoplasms with histological findings similar to recurrent nevi
      occurring in all types of EB. They often mimic melanoma clinically,
      dermatoscopically, and histopathologically. The ability to recognize an EB nevus
      is essential for appropriate management of the patient. Unnecessary surgical
      excision in patients with already high-risk EB should be avoided. Close
      monitoring of these lesions is recommended because no cases of transformation to
      melanoma have been described.

PMID- 25051105
TI  - Multiple localized epidermolytic acanthomas of the vulva associated with vulvar
      pruritus: a case report.
AB  - Epidermolytic acanthoma (EA) is a rare benign acquired tumor that most commonly
      presents as a solitary lesion on the trunk, extremities, male genitalia, and face
      with a male predominance. Cases occurring on the female genitalia have rarely
      been reported. We describe the case of multiple localized EAs occurring on the
      vulva of a 31-year-old woman presenting with the chief complaint of vulvar
      pruritus. Although rare to occur in the vulvar area, EAs should be included in
      the differential diagnosis of multiple vulvar papules.

PMID- 25051106
TI  - Acral Mycosis Fungoides With Epidermal Microvesiculation Mucinosis.
AB  - Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell
      lymphoma. This entity may present with a wide spectrum of clinicopathological
      manifestations and mimic different dermatoses. Among its histopathological
      variants, spongiosis is an infrequent finding, and spongiotic microvesiculation
      is particularly rare. Mucinous deposition is a common event in folliculosebaceous
      units of folliculotropic MF but rarely described within the epidermis. Herein, we
      report a patient with eczematous palmoplantar lesions whereby the histological,
      immunohistochemical, and molecular studies confirmed to be a unique case of MF
      showing epidermal microvesiculation mucinosis. 

PMID- 25051107
TI  - Extradigital Symplastic Glomus Tumor of the Hand: Report of 2 Cases and
      Literature Review.
AB  - Glomus tumor is a rather common tumor of the hand, which presents with a classic
      triad of symptoms of high temperature, sensitivity and pain, and localized
      tenderness. Most glomus tumors are located in the digits, especially in
      subungueal areas. However, extradigital tumors are less frequent, and little is
      known about their clinical and histopathological features. Two cases of
      extradigital symplastic glomus tumor are presented. An active clinical and
      pathological awareness to avoid misdiagnosis or delayed diagnosis of this
      uncommon lesion is highlighted. 

PMID- 25051108
TI  - Is Tumor of Follicular Infundibulum a Reaction to Dermal Scarring?
AB  - Tumor of follicular infundibulum (TFI) is currently believed to be a benign
      epithelial neoplasm with follicular differentiation. It has been suggested that
      TFI is associated with dermal scarring, but further investigation is needed to
      confirm this correlation. To approach this question, a retrospective study was
      presented, a total of 67 cases (64 lesions) were found in a search covering cases
      over a 10-year period. Overall, the presence of histological dermal scarring was
      noted in 34 of 64 (53.13%) cases. Of the cases where TFI was an incidental
      finding, the presence of dermal scarring was noted in 13 of 18 (72.22%) cases.
      Meanwhile, of the cases where TFI was the main diagnosis, the presence of dermal
      scarring was noted in 12 of 34 (35.29%) cases. This suggests that TFI may, in
      some cases, represent an epidermal reaction pattern to dermal scarring. 

PMID- 25051109
TI  - A clinicopathologic and immunohistochemical study of 7 cases of sclerosing
      perineurioma.
AB  - Sclerosing perineurioma is a relatively rare tumor that has remained widely
      unknown since first reported by Fetsch in 1997. To our knowledge, no large or
      small series of claudin-1 in sclerosing perineurioma has been confirmed to date.
      We collected 7 new cases of sclerosing perineurioma. Six patients were female,
      and 1 was male. The patients' age ranged from 15 to 58 years (mean, 36.6 years;
      median, 42.0 years). The primary reason for consultation at the outpatient
      clinics was a slowly enlarging mass. The preoperative durations were available
      for 4 of the 7 cases and ranged from 2 to 7 years. Six tumors were located in the
      fingers, and the other tumor was found in the palm. The sizes ranged from 4 to 12
      mm in diameter (mean, 6.7 mm; median, 6.0 mm). Microscopically, all tumors were
      nodular lesions, with sclerotic stroma involving reticular dermis primarily
      consisting of small oval epithelioid cells and plump spindle cells, scattered and
      arranged in corded, trabecular, reticular, and/or whorled growth patterns. The
      neoplastic cells were immunoreactive for epithelial membrane antigen (7 of 7) and
      glucose transporter 1 (7 of 7). The periodic acid-Schiff reaction and positive
      immunostaining for type IV collagen were observed directly adjacent to the
      lesional cells in all cases (6 of 6). Claudin-1 immunostaining was positive in
      all 7 cases, suggesting that claudin-1 may serve as a helpful diagnostic marker
      for sclerosing perineurioma.

PMID- 25051110
TI  - Fabrication and structure analysis of poly(lactide-co-glycolic acid)/silk fibroin
      hybrid scaffold for wound dressing applications.
AB  - Silk fibroin (SF) and poly(lactide-co-glycolic acid) (PLGA) have been proved to
      be invaluable polymers in the field wound healing. This study aims at optimizing
      the electrospinning process of those polymers to make a hybrid membrane as a
      chronic wounds dressing. After characterizing the scaffolds, PLGA/SF (2:1), and
      PLGA scaffolds were selected for further study according to their superior
      tensile mechanical properties. The attachment and proliferation of mouse
      fibroblasts (L929) on scaffolds were measured using colorimetric assay and
      scanning electron microscopy. Furthermore, to evaluate the wound healing effect
      of the scaffolds in comparison with gauze and Comfeel((r)) dressings, an excision
      wound model was conducted on diabetic rats. On the postoperative days of 3, 6, 9,
      12, and 15, residual wound area was calculated using macroscopic data. In vitro
      results showed that the attachment and proliferation of L929 were significantly
      increased on PLGA/SF (2:1) hybrid scaffold. Animal study and histopathological
      evaluation outcomes confirmed the in vitro results as well. On day 15, the
      residual wound area in PLGA/SF (2:1) hybrid membrane group was significantly
      smaller than PLGA and control groups. This promising scaffold has the potential
      to be used for the upcoming development of wound dressings with or without
      biological drugs. 

PMID- 25051111
TI  - The influence of phospholipid on the physicochemical properties and anti-tumor
      efficacy of liposomes encapsulating cisplatin in mice bearing C26 colon
      carcinoma.
AB  - SPI-077, cisplatin stealth liposome, is the best illustration of poor cisplatin
      release from liposomes and the subsequent negligible therapeutic activity. For
      this reason, optimizing drug release kinetics is desirable. In this report,
      cisplatin was encapsulated in liposomes composed of different
      phosphatidylcholines with various phase transition temperatures (Tm) (HSPC, DPPC,
      DMPC, soy phosphatidylcholine (SPC)), cholesterol and mPEG2000-DSPE. In vitro
      cytotoxicity studies indicated that lowering Tm of lipids increases cisplatin
      release; the highest cytotoxicity was observed in SPCs. Cisplatin plasma
      concentration was also sensitive to the transition temperature. The highest
      platinum concentration observed after treatment with HSPC and DPPC liposomes,
      whilst the lowest was observed with SPC. HSPC and DPPC containing liposomes
      showed the highest therapeutic efficacy and survival with DPPC exhibited better
      efficacy in mouse model of C26. It seems that DPPC with Tm (41.5 degrees C)
      nearly, or close to body temperature maintains good drug retention in blood
      circulation. Upon extravasation through permeable tumor microvasculature, it
      gradually releases its payload in the tumor area better than HSPC, with a greater
      Tm of 55 degrees C. Our data suggests, the choice of Tm for lipid mixture
      directed to a considerable extent the rate of cisplatin elimination from plasma
      and therapeutic effects. 

PMID- 25051112
TI  - Topotecan-tamoxifen duple PLGA polymeric nanoparticles: investigation of in
      vitro, in vivo and cellular uptake potential.
AB  - The dual drug loaded poly(dl-lactic-co-glycolic acid) (PLGA(1)) nanoparticles
      (TOP-TAM NPs(2)) concurrently delivering topotecan hydrochloride (TOP(3)) and
      tamoxifen citrate (TAM(4)) were developed to achieve synergism for the treatment
      of breast cancer by enhancing the permeation of TOP through the gut and the cells
      present in the breast. TAM acted as P-glycoprotein (P-gp(5)) inhibitor, reduced
      the side effects of individual drugs by reducing the dose. The NPs were prepared
      by double emulsion (w/o/w) method. The optimized TOP-TAM NPs were found to have
      smooth and spherical morphology by using SEM(6) and TEM(7) technique. Similarly
      size of nanoparticles was found to be 151.2 +/- 1.6 nm with 0.147 +/- 0.03
      polydispersity index (PDI(8)). The percentage entrapment efficiency of 95.17 +/-
      3.57 and 57.77 +/- 2.2 was found for TAM and TOP respectively. The lyophillized
      nanoparticles under DSC(9) showed amorphous nature of both TOP and TAM. In an in
      vitro release study the release of drugs from TOP-TAM NPs was found to follow the
      Higuchi pattern. The ex vivo gut permeation study revealed that the TAM enhanced
      the permeation of TOP and increased its bioavailability by 1.9 folds. The
      permeation and activity of combination of drugs were further confirmed by
      carrying out cell line studies on MCF-7 cells.

PMID- 25051113
TI  - Specific and efficient gene delivery mediated by an asialofetuin-associated
      nanosystem.
AB  - Gene therapy is considered a promising approach for the treatment of
      hepatocellular carcinoma (HCC). In this regard, the main goal of this work was to
      develop a specific and efficient gene delivery nanosystem to HCC based on 1
      palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol cationic
      liposomes and asialofetuin (ASF), a specific ligand to the asialoglycoprotein
      receptor (ASGP-R) that is overexpressed in HCC. Our results show that association
      of ASF to lipoplexes promotes a substantial increase in their biological activity
      in HCC cells, not only in vitro, but also in an animal model. The transfection
      activity obtained with this novel nanosystem (ASF-lipoplexes) was much higher
      than that observed with a highly efficient commercial formulation. On the other
      hand, the presence of high concentrations of galactose substantially reduced the
      cell uptake and biological activity of the ASF-lipoplexes. These results,
      together with those obtained in the presence of inhibitors of endocytosis, show
      that the potentiation induced by the association of ASF to lipoplexes is due to
      its specific interaction with the ASGP-R. The physicochemical properties of the
      generated nanosystem also reinforce this observation. Overall, our results
      demonstrate for the first time that the novel ASF-lipoplexes present a noticeable
      ability to specifically and efficiently deliver genetic material into HCC cells. 

PMID- 25051114
TI  - Increasing the dissolution rate and oral bioavailability of the poorly water
      soluble drug valsartan using novel hierarchical porous carbon monoliths.
AB  - In the present study, a novel hierarchical porous carbon monolith (HPCM) with
      three-dimensionally (3D) ordered macropores (~ 400 nm) and uniform accessible
      mesopores (~ 5.2 nm) was synthesized via a facile dual-templating technique using
      colloidal silica nanospheres and Poloxamer 407 as templates. The feasibility of
      the prepared HPCM for oral drug delivery was studied. Valsartan (VAL) was chosen
      as a poorly water-soluble model drug and loaded into the HPCM matrix using the
      solvent evaporation method. Scanning electron microscopy (SEM) and specific
      surface area analysis were employed to characterize the drug-loaded HPCM-based
      formulation, confirming the successful inclusion of VAL into the nanopores of
      HPCM. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC)
      demonstrated that the incorporated drug in the HPCM matrix was in an amorphous
      state and the VAL formulation exhibited good physical stability for up to 6
      months. In vitro tests showed that the dissolution rate of HPCM-based formulation
      was increased significantly compared with that of crystalline VAL or VAL-loaded
      3D ordered macroporous carbon monoliths (OMCMs). Furthermore, a pharmacokinetic
      study in rats demonstrated about 2.4-fold increase in oral bioavailability of VAL
      in the case of HPCM-based formulation compared with the commercially available
      VAL preparation (Valzaar((r))). These results therefore suggest that HPCM is a
      promising carrier able to improve the dissolution rate and oral bioavailability
      of the poorly water-soluble drug VAL.

PMID- 25051115
TI  - KLF5 promotes hypoxia-induced survival and inhibits apoptosis in non-small cell
      lung cancer cells via HIF-1alpha.
AB  - Transcription factor Kruppel-like factors 5 (KLF5) is overexpressed in a wide
      range of tumor tissues and acts as a prognostic factor in cancer. However, the
      role of KLF5 in non-small cell lung cancer is not clear. Hypoxia plays a vital
      part in the development of cancer via hypoxia-inducible factor 1 (HIF-1). Our
      study showed that hypoxia (1% O2) increased cell viability, clonality and
      proliferation and inhibited cell apoptosis in A549 cells. The expression of HIF
      1alpha and KLF5 was increased time-dependently in hypoxia. Using small
      interfering RNA (siRNA) targeting KLF5 or HIF-1alpha, we demonstrated that KLF5
      or HIF-1alpha knockdown inhibited hypoxia-induced cell survival and promoted cell
      apoptosis by actively downregulating cyclin B1, survivin and upregulating caspase
      3. Given the similar effect of KLF5 and HIF-1alpha on cell survival, an attempt
      was made to investigate the putative interaction of them in hypoxia. KLF5 was
      revealed to co-immunoprecipitate with HIF-1alpha and hypoxia increased the amount
      of KLF5 and HIF-1alpha complex. Moreover, silencing of KLF5 decreased HIF-1alpha
      expression while KLF5 was not affected by HIF-1alpha inhibition in hypoxia,
      confirming the effect of KLF5 on upregulation of HIF-1alpha. In conclusion, this
      study identified hypoxia as a tumor promoter by triggering KLF5 -> HIF-1alpha ->
      cyclin B1/survivin/caspase-3 in lung cancer cells. 

PMID- 25051116
TI  - Cytokine and nitric oxide levels in patients with sepsis--temporal evolvement and
      relation to platelet mitochondrial respiratory function.
AB  - BACKGROUND: The levels of nitric oxide (NO) and various cytokines are known to be
      increased during sepsis. These signaling molecules could potentially act as
      regulators and underlie the enhancement of mitochondrial function described in
      the later phase of sepsis. Therefore, we investigated the correlation between
      observed changes in platelet mitochondrial respiration and a set of pro- and anti
      inflammatory cytokines as well as NO plasma levels in patients with sepsis.
      METHODS AND RESULTS: Platelet mitochondrial respiration and levels of TNFalpha,
      MCP-1 (monocyte chemotactic protein-1), INFgamma (interferon-gamma), IL-1beta, IL
      4, IL-5, IL-6, IL-8, IL-10 and IL-17 and NO were analyzed in 38 patients with
      severe sepsis or septic shock at three time points during one week following
      admission to the ICU. Citrate synthase, mitochondrial DNA and cytochrome c were
      measured as markers of cellular mitochondrial content. All mitochondrial
      respiratory states increased over the week analyzed (p<0.001). IL-8 levels
      correlated with maximal mitochondrial respiration on day 6-7 (p = 0.02, r2 =
      0.22) and was also higher in non-survivors compared to survivors on day 3-4 and
      day 6-7 (p = 0.03 respectively). Neither NO nor any of the other cytokines
      measured correlated with respiration or mortality. Cytochrome c levels were
      decreased at day 1-2 by 24 +/- 5% (p = 0.03) and returned towards values of the
      controls at the last two time points. Citrate synthase activity and mitochondrial
      DNA levels were similar to controls and remained constant throughout the week.
      CONCLUSIONS: Out of ten analyzed cytokines and nitric oxide, IL-8 correlated with
      the observed increase in mitochondrial respiration. This suggests that cytokines
      as well as NO do not play a prominent role in the regulation of platelet
      mitochondrial respiration in sepsis. Further, the respiratory increase was not
      accompanied by an increase in markers of mitochondrial content, suggesting a
      possible role for post-translational enhancement of mitochondrial respiration
      rather than augmented mitochondrial mass.

PMID- 25051118
TI  - Imaging, photophysical properties and DFT calculations of manganese blue (barium
      manganate(VI) sulphate)--a modern pigment.
AB  - Manganese blue is a synthetic barium manganate(VI) sulphate compound that was
      produced from 1935 to the 1990s and was used both as a blue pigment in works of
      art and by conservators in the restoration of paintings. The photophysical
      properties of the compound are described as well as the setup needed to record
      the spatial distribution of the pigment in works of art.

PMID- 25051117
TI  - What's in a name? The characterization of pure alexia.

PMID- 25051119
TI  - Mechanisms and potential molecular markers of early response to combination
      epigenetic therapy in patients with myeloid malignancies.
AB  - Combination epigenetic treatment (EGT) utilizing DNA methyl transferase
      inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) may be more
      efficacious than single agent treatment in myelodysplastic syndromes (MDS) and
      acute myeloid leukemia (AML). The molecular mechanisms behind the potential
      clinical efficacy of combination EGT treatment are incompletely understood and
      the frequently lengthy EGT regimes required to determine clinical response have
      generated a significant demand for early molecular markers of treatment response.
      Our study aimed to identify the effect of combination azacitidine (AZA) and
      panobinostat (LBH589) on expression levels of a panel of genes implicated in the
      pathogenesis of high-risk MDS or AML in HL-60 cells. We also characterized gene
      expression profiles in peripheral blood mononuclear (PBMCs) from patients in a
      recently reported phase Ib/II clinical trial using the combination of AZA and
      LBH589 and correlated these findings with clinical response to treatment. In
      vitro analysis demonstrated increased expression of caspase-3, Nor-1, NUR77,
      p15INK4B and p21WAF1/CIP1 and decreased expression of Bcl-xL in HL-60 cells
      treated with combination EGT. Analysis of patient samples prior to treatment
      demonstrated a significant reduction in NUR77 and p21WAF1/CIP1 expression
      compared to healthy controls. NUR77 and p21WAF1/CIP1 levels were similar between
      treatment non-responders and responders at screening. Early post first cycle
      treatment (day 25) analysis demonstrated a significant increase in expression of
      both NUR77, and p21WAF1/CIP1. A significant increase in NUR77, and p21WAF1/CIP1
      together with a trend to increase in p15INK4B first cycle expression was observed
      in treatment responders compared to non-responders. In summary, combination AZA
      and LBH589 epigenetic treatment is associated with in vitro and in vivo
      modulation of genes implicated in the pathogenesis of MDS/AML. Early expression
      of NUR77 and p21WAF1/CIP1 correlated with clinical response to combination EGT
      suggesting investigation for potential use as molecular markers of early
      treatment response may be warranted. 

PMID- 25051120
TI  - Implementation of focused ion beam (FIB) system in characterization of nuclear
      fuels and materials.
AB  - Beginning in 2007, a program was established at the Idaho National Laboratory to
      update key capabilities enabling microstructural and micro-chemical
      characterization of highly irradiated and/or radiologically contaminated nuclear
      fuels and materials at scales that previously had not been achieved for these
      types of materials. Such materials typically cannot be contact handled and pose
      unique hazards to instrument operators, facilities, and associated personnel.
      Over the ensuing years, techniques have been developed and operational experience
      gained that has enabled significant advancement in the ability to characterize a
      variety of fuel types including metallic, ceramic, and coated particle fuels,
      obtaining insights into in-reactor degradation phenomena not achievable by any
      other means. The following article describes insights gained, challenges
      encountered, and provides examples of unique results obtained in adapting dual
      beam FIB technology to nuclear fuels characterization. 

PMID- 25051121
TI  - Analysis of microscopic parameters of surface charging in polymer caused by
      defocused electron beam irradiation.
AB  - The relationship between microscopic parameters and polymer charging caused by
      defocused electron beam irradiation is investigated using a dynamic scattering
      transport model. The dynamic charging process of an irradiated polymer using a
      defocused 30 keV electron beam is conducted. In this study, the space charge
      distribution with a 30 keV non-penetrating e-beam is negative and supported by
      some existing experimental data. The internal potential is negative, but
      relatively high near the surface, and it decreases to a maximum negative value at
      z=6 MUm and finally tend to 0 at the bottom of film. The leakage current and the
      surface potential behave similarly, and the secondary electron and leakage
      currents follow the charging equilibrium condition. The surface potential
      decreases with increasing beam current density, trap concentration, capture cross
      section, film thickness and electron-hole recombination rate, but with decreasing
      electron mobility and electron energy. The total charge density increases with
      increasing beam current density, trap concentration, capture cross section, film
      thickness and electron-hole recombination rate, but with decreasing electron
      mobility and electron energy. This study shows a comprehensive analysis of
      microscopic factors of surface charging characteristics in an electron-based
      surface microscopy and analysis.

PMID- 25051122
TI  - Singlet oxygen and ROS in a new light: low-dose subcellular photodynamic
      treatment enhances proliferation at the single cell level.
AB  - Two-photon excitation of a sensitizer with a focused laser beam was used to
      create a spatially-localized subcellular population of reactive oxygen species,
      ROS, in single HeLa cells. The sensitizer used was protoporphyrin IX, PpIX,
      endogenously derived from 5-aminolevulinic acid delivered to the cells. Although
      we infer that singlet oxygen, O2(a(1)Deltag), is one ROS produced upon
      irradiation of PpIX under these conditions, it is possible that the superoxide
      ion, O2(-), may also play a role in this system. With a "high" dose of PpIX
      sensitized ROS, the expected death of the cell was observed. However, under "low
      dose" conditions, clear signs of cell proliferation were observed. The present
      results facilitate studies of ROS-mediated signalling in imaging-based single
      cell experiments.

PMID- 25051123
TI  - Temperature dependence of electrical transport in a pressure-sensitive
      nanocomposite.
AB  - Printed nanocomposites are of significant application potential in numerous
      technologies, such as touch-sensitive sensors and surfaces. Here, temperature
      dependent electrical transport measurements were undertaken on a recently
      developed screen-printed, multicomponent, nanocomposite ink to develop a detailed
      understanding of the electrical transport mechanisms. A theoretical model
      combining contributions from linear percolative conduction and nonlinear
      conduction attributed to field-assisted quantum tunneling successfully describes
      the temperature dependent conduction observed. 

PMID- 25051124
TI  - Effects of different doses of caffeine on anaerobic exercise in boys.
AB  - This study investigated effects of low (1 mg.kg-1), moderate (3 mg.kg-1) and high
      (5 mg.kg-1) doses of caffeine on anaerobic performance in boys. Twenty-six 8- to
      10-year-old boys participated in a double-blind, crossover, counter-balanced
      study. Boys received in random order a placebo (PL) or anhydrous caffeine: 1 (CAF
      1), 3 (CAF-3), or 5 (CAF-5) mg caffeine.kg-1 body mass in cherry flavored Sprite.
      Sixty minutes following consumption boys performed a static handgrip test and
      then a 30-s Wingate test. Maximal grip strength (21.5 +/- 4.9 & 21.6 +/- 4.7 vs.
      20.4 +/- 4.0 kg) was significantly higher in CAF-5 & CAF-3 vs PL, respectively.
      Absolute and relative peak power (287 +/- 72 vs 281 +/- 69 W & 8.0 +/- 0.9 vs 7.8
      +/- 1.0 W.kg-1) were significantly higher in CAF-3 vs PL, respectively. Mean
      power (153 +/- 48 vs 146 +/- 43 W) was significantly higher in CAF-5 vs PL,
      respectively. Peak Wingate HR was significantly higher (189 +/- 8 vs 185 +/- 9
      beats.min-1) in CAF-5 vs PL, respectively. These findings suggest that in boys
      CAF-1 did not affect performance. During the Wingate test CAF-3 resulted in
      higher peak power while CAF-5 increased mean power. The significant increase in
      peak HR following the Wingate test is likely related to greater mean power
      generated during CAF-5. 

PMID- 25051125
TI  - Multimodality imaging in transcatheter aortic valve replacement.
AB  - Transcatheter aortic valve replacement is a major advance that has dramatically
      changed our approach to elderly patients with severe aortic stenosis. This
      advance has been made possible by innovative device and delivery improvements,
      coupled with rapid developments in multimodality imaging. Multimodality imaging
      draws from multiple imaging fields and is central to patient evaluation and
      treatment. The primary modalities to date include transthoracic echocardiography
      and transesophageal echocardiography, computed tomography, and fluoroscopy. Each
      of these modalities carries a different weight in the various stages of patient
      selection, procedural guidance, monitoring, and follow-up. Multimodality imaging
      ensures optimal device selection, delivery, and patient safety, and will continue
      to advance as the next generation of aortic valve devices further advance
      cardiovascular care. 

PMID- 25051126
TI  - Management of hypercholesterolemia for prevention of atherosclerotic
      cardiovascular disease: focus on the potential role of recombinant anti-PCSK9
      monoclonal antibodies.
AB  - Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and
      disability in the United States and other developed nations, and is rising
      rapidly in the rest of the world. Low-density lipoprotein (LDL) is the major
      atherogenic particle in most patients at high risk for ASCVD events, and statin
      based LDL-lowering treatment is the major focus of treatment for prevention of
      ASCVD. Despite this, an estimated 57 million US adults (25%) still have
      moderately elevated levels of LDL-cholesterol (LDL-C) > 160 mg/dL, and many
      others have an LDL-C above the level considered appropriate for their high-risk
      status. Although statins are very effective for lowering LDL-C, and other classes
      of LDL-lowering medications are available, many patients still cannot achieve
      adequate LDL-lowering with maximal tolerated doses of US Food and Drug
      Administration-approved treatments. Thus, there is an unmet medical need for
      statin adjuncts in these patients, as well as for statin alternatives in statin
      intolerant patients. A recently discovered human protein, proprotein convertase
      subtilisin/kexin type 9 (PCSK9), plays an important role in LDL metabolism by
      promoting degradation of the LDL receptor, and thus reducing clearance of LDL and
      increasing LDL-C levels. Accordingly, inhibition of PCSK9 activity has become an
      attractive target for drug development for lowering LDL-C, and human monoclonal
      antibodies against PCSK9, are now in late-stage clinical development. These
      antibodies are at least as effective as statins for LDL-C lowering (or more so),
      and their effects are additive to those of statins. To date, they have been well
      tolerated and apparently safe in clinical trials. Long-term randomized,
      controlled trials of their safety, tolerability, and ability to reduce ASCVD are
      now underway. 

PMID- 25051127
TI  - Height and heart disease.
AB  - Height has a relationship with a number of medical conditions, including heart
      disease. Atrial fibrillation has been observed to be more common in taller
      individuals. Marfan syndrome, with its high prevalence of mitral valve disease
      and abnormalities of the aorta, is associated with increased height. Mitral valve
      prolapse in patients without Marfan syndrome may be more common in taller people.
      Conversely, congestive heart failure, coronary artery disease, and possibly
      aortic valve calcification are less prevalent with increasing height. The
      relationship between height and health will be of increasing importance as the
      population grows taller. 

PMID- 25051128
TI  - Lomitapide for the management of homozygous familial hypercholesterolemia.
AB  - Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder of low
      density lipoprotein cholesterol (LDL-C) metabolism resulting in extremely
      elevated serum levels of LDL-C and premature atherosclerotic cardiovascular
      disease. Treatment typically involves multiple pharmacologic agents, as well as
      mechanical filtration using weekly or biweekly LDL apheresis. Despite combination
      lipid-lowering therapy, LDL-C levels and cardiovascular morbidity and mortality
      remain unacceptably high in HoFH patients. The European Commission and the US
      Food and Drug Administration approved the use of lomitapide, a novel medication
      designed to address this significant unmet need. Lomitapide is an orally
      administered inhibitor of microsomal triglyceride transfer protein that is
      indicated as an adjunct to a low-fat diet and other lipid-lowering treatments,
      including LDL apheresis where available for the reduction of LDL-C, total
      cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol in
      adult patients with HoFH. The risks of transaminase elevations, hepatic
      steatosis, and gastrointestinal side effects, and the potential for drug
      interactions, require vigilant examination of the clinical and laboratory data
      and patient counseling prior to initiation of lomitapide, as well as regular
      monitoring during follow-up care. This article highlights important practical
      considerations for the use of lomitapide in the context of the evaluation and
      management of a HoFH patient case. 

PMID- 25051129
TI  - The current and future landscape of urinary thromboxane testing to evaluate
      atherothrombotic risk.
AB  - Biomarker testing for efficacy of therapy is an accepted way for clinicians to
      individualize dosing to genetic and/or environmental factors that may be
      influencing a treatment regimen. Aspirin is used by nearly 43 million Americans
      on a regular basis to reduce risks associated with various atherothrombotic
      diseases. Despite its widespread use, many clinicians are unaware of the link
      between suboptimal response to aspirin therapy and increased risk for inferior
      clinical outcomes in several disease states, and biomarker testing for efficacy
      of aspirin therapy is not performed as routinely as efficacy testing in other
      therapeutic areas. This article reviews the clinical and laboratory aspects of
      determining whole-body thromboxane production, particularly as it pertains to
      efficacy assessment of aspirin responsiveness. 

PMID- 25051130
TI  - Global T-wave inversion on electrocardiogram: what is the differential?
AB  - Global T-wave inversion as seen on electrocardiogram is associated with a variety
      of pathophysiologic states, including cardiac, pulmonary, and cerebrovascular
      disease, and acute electrolyte disorders. Although some of these are chronic
      conditions, others are acute emergencies, necessitating early diagnosis and
      treatment. This article reviews and provides examples of possible etiologies of
      global T-wave inversion on electrocardiogram. 

PMID- 25051131
TI  - Left atrial appendage occlusion with the WATCHMANTM for stroke prevention in
      atrial fibrillation.
AB  - Atrial fibrillation (AF) is a major cause of stroke and systemic embolism.
      Although warfarin and the novel oral anticoagulants reduce thromboembolic risk,
      they are associated with an ongoing bleeding hazard, in addition to other
      limitations that deter their use. The left atrial appendage (LAA) appears to be
      the primary source of thrombus in AF; therefore, LAA closure represents a
      mechanical strategy for stroke prevention in these patients. The WATCHMANTM LAA
      closure device (Boston Scientific, Natick, MA) is a nitinol-framed occluder that
      is implanted percutaneously under echocardiographic and fluoroscopic guidance.
      Data from two randomized clinical trials support the clinical efficacy of
      transcatheter LAA occlusion with the WATCHMAN and demonstrate that procedural
      safety has improved significantly since initial experience. This article
      summarizes the rationale, procedural technique, safety, and clinical efficacy of
      the WATCHMAN device in patients with AF at high risk for thromboembolic events. 

PMID- 25051132
TI  - Coronary artery fistulae.
AB  - Coronary artery fistulae and coronary cameral fistulae are rare anomalies that
      are discovered incidentally in patients undergoing coronary angiography. This
      article reviews the classification, management, and complications of these
      fistulae, and discusses a variety of presentations. 

PMID- 25051133
TI  - Therapeutic potentials of phosphodiesterase-5 inhibitors in cardiovascular
      disease.
AB  - Phosphodiesterase-5 (PDE5) inhibitors have been approved by the US Food and Drug
      Administration for the treatment of erectile dysfunction and more recently for
      pulmonary arterial hypertension (World Health Organization functional class I).
      PDE5 inhibitors can induce vasodilation; in addition, through a complex pathway
      involving nitric oxide, cyclic guanosine monophosphate, and protein kinase G, it
      can reduce apoptosis and suppress cell proliferation. The presence of PDE5
      inhibitors in various tissues and systemic vasculature make them potential
      targets in a variety of cardiovascular diseases. In many in vitro and in vivo
      studies, PDE5 inhibitors have been shown to have positive effects in systolic and
      diastolic congestive heart failure, ischemic heart disease, doxorubicin
      cardiomyopathy, and pulmonary arterial hypertension. They also improved
      vasoconstriction in Raynaud phenomenon, peripheral artery disease, and hypoxic
      brain conditions. This article reviews the therapeutic potentials of PDE5
      inhibitors in different cardiovascular diseases. 

PMID- 25051134
TI  - Influenza and coronary artery disease: exploring a clinical association with
      myocardial infarction and analyzing the utility of vaccination in prevention of
      myocardial infarction.
AB  - Both coronary artery disease and influenza outbreaks contribute significantly to
      worldwide morbidity and mortality. An increasing number of epidemiologic studies
      have concluded that a temporal association exists between acute viral illnesses
      and myocardial infarction. Viral illnesses such as influenza can cause or
      exacerbate coronary atherosclerosis by activating inflammatory pathways. Data
      from a large case-controlled trial and two randomized controlled trials suggest
      that influenza vaccination in patients with coronary artery disease may lead to a
      decrease in incidence, morbidity, and mortality from acute myocardial infarction.
      A meta-analysis of the two randomized controlled trials for cardiovascular death
      demonstrated a pooled relative risk of 0.39 (95% confidence interval, 0.20-0.77)
      for patients who received the influenza vaccine compared with placebo. 

PMID- 25051135
TI  - Coronary revascularization: then, now, future trends.

PMID- 25051136
TI  - ACC.14: update on the prevention, diagnosis, and treatment of cardiovascular
      disease.

PMID- 25051137
TI  - Subclavian artery stenosis: a case series and review of the literature.
AB  - Subclavian artery stenosis (SAS) is a significant form of peripheral artery
      disease, which may be a marker of diffuse atherosclerosis and increased risk for
      cardiovascular events. SAS can lead to symptomatic ischemia affecting the upper
      extremities, the brain, and, in some cases, the heart. In general, asymptomatic
      subclavian artery disease is treated with medical therapy and invasive treatment
      is reserved for the more symptomatic patients. This article discusses the
      evaluation of four patients with varying presentations of subclavian artery
      disease. 

PMID- 25051138
TI  - Intramolecular indicator displacement assay for anions: supramolecular sensor for
      glyphosate.
AB  - One of the well-known strategies for anion sensing is an indicator (dye)
      displacement assay. However, the disadvantage of the dye displacement assays is
      the low sensitivity due to the excess of the dye used. To overcome this setback,
      we have developed an "Intramolecular Indicator Displacement Assay (IIDA)". The
      IIDAs comprise a receptor and a spacer with an attached anionic chromophore in a
      single-molecule assembly. In the resting state, the environment-sensitive anionic
      chromophore is bound by the receptor, while the anionic substrate competes for
      binding into the receptor. The photophysical properties of the dye exhibit change
      in fluorescence when displaced by anions, which results in cross-reactive
      response. To illustrate the concept, we have prepared IID sensors 1 and 2. Here,
      the characterization of sensors and microtiter arrays comprising the IIDA are
      reported. The microtiter array including IID sensors 1 and 2 is capable of
      recognizing biological phosphates in water. The utility of the IIDA approach is
      demonstrated on sensing of a phosphonate herbicide glyphosate and other
      biologically important anions such as pyrophosphate in the presence of
      interferent sodium chloride. 

PMID- 25051139
TI  - Sulforaphane and prostate cancer interception.
AB  - Whereas much attention is focused on distinguishing newly diagnosed prostate
      cancers that will progress to become aggressive forms of the disease from those
      that will remain indolent, it is also appropriate to explore therapeutic and
      lifestyle interventions to reduce the risk of progression. Diets rich in broccoli
      have been associated with a reduction in risk of progression, which has been
      attributed to the compound sulforaphane. Although the mode of action of
      sulforaphane has been extensively studied in cell and animal models and a
      multiple of mechanisms that could underpin its protective effects have been
      proposed, recent evidence from human intervention studies suggests that
      sulforaphane is involved in a complex interplay between redox status and
      metabolism to result in a tissue environment that does not favour prostate cancer
      progression. 

PMID- 25051140
TI  - Functional evaluation of key interactions evident in the structure of the
      eukaryotic Cys-loop receptor GluCl.
AB  - The publication of the first high-resolution crystal structure of a eukaryotic
      Cys-loop receptor, GluClalpha, has provided valuable structural information on
      this important class of ligand-gated ion channels (LGIC). However, limited
      functional data exist for the GluCl receptors. Before applying the structural
      insights from GluCl to mammalian Cys-loop receptors such as nicotinic
      acetylcholine and GABA receptors, it is important to ensure that established
      functional features of mammalian Cys-loop receptors are present in the more
      distantly related GluCl receptors. Here, we seek to identify ligand-binding
      interactions that are generally associated with Cys-loop receptors, including the
      frequently observed cation-pi interaction. Our studies were performed on the
      highly homologous GluClbeta receptor, because GluClalpha is not activated by
      glutamate in Xenopus laevis oocytes. Mutagenesis of the signal peptide and pore
      lining helix was performed to enhance functional expression and sensitivity to
      applied ligand, respectively. Conventional and unnatural amino acid mutagenesis
      indicate a strong cation-pi interaction between Y206 and the protonated amine of
      glutamate, as well as other important ionic and hydrogen bond interactions
      between the ligand and the binding site, consistent with the crystal structure. 

PMID- 25051141
TI  - Tg(Grm1) transgenic mice: a murine model that mimics spontaneous uveal melanoma
      in humans?
AB  - Although rare, uveal melanoma (UM) is the most common primary intraocular tumor
      in adults. About half of UM patients develop metastatic disease typically in the
      liver and die within a short period, due to ineffective systemic therapies. UM
      has unique and distinct genetic features predictive of metastasis. Animal models
      are required to improve our understanding of therapeutic options in disseminated
      UM. Since spontaneous murine UM models are lacking, our aim was to analyze the
      suitability of the established transgenic melanoma mouse model Tg(Grm1) as a new
      UM model system. We demonstrated that adult Grm1 transgenic mice develop
      choroidal thickening and uveal melanocytic neoplasia with expression of the
      melanocytic markers S100B and MelanA. Further, we showed that GRM1 is expressed
      in human UM, similar to skin melanoma. This study presents a new mouse model for
      spontaneous UM and suggests that the glutamate signaling pathway is a possible
      target for UM therapy. 

PMID- 25051142
TI  - Paclitaxel-loaded trimethyl chitosan-based polymeric nanoparticle for the
      effective treatment of gastroenteric tumors.
AB  - Gastroenteric cancer is one of the most prevalent cancers and is responsible for
      most cancer-related deaths worldwide. Paclitaxel (PTX), a classical microtubule
      inhibitor, is indicated in the treatment of gastric/gastroenteric cancers. In the
      present study, trimethyl chitosan (TMC)-loaded PTX (TMC-PTX) was prepared and
      evaluated for its therapeutic effect in gastric cancers. A spherical shaped
      nanosized TMC-PTX particle was formed with high loading capacity (~30%) for PTX.
      The nanoparticles (NPs) showed a sustained release pattern (~70%) for up to 96 h
      of study period. The positively charged NPs were preferentially internalized by
      Caco-2 cells. TMC-PTX inhibited the gastric cell proliferation with an IC50 value
      of 0.6 ug in NCI-N87 cells while it was 1.26 ug in the SGC-7901 cell line after
      24 h exposure. The apoptosis assay (Annexin V/PI) showed a large presence of
      cells in the early and late apoptosis chamber, while cell cycle analysis showed a
      marked G2/M phase arrest (50-60%) in NCI-N87 and SGC-7901 cell lines indicating
      its potent anti-proliferative effect. The in vivo antitumor study in NCI-N87 and
      SGC-7901 bearing xenograft model showed a superior chemotherapeutic efficacy for
      TMC-PTX NP. The NP group significantly reduced the tumor growth with no obvious
      sign of systemic side-effects (safety). Collectively, our results suggest that
      the microtubule inhibitory effect of PTX-loaded polymer NP could be a promising
      system for the treatment of gastroenteric cancers. 

PMID- 25051143
TI  - Uranium immobilization in an iron-rich rhizosphere of a native wetland plant from
      the Savannah River Site under reducing conditions.
AB  - The hypothesis of this study was that iron plaques formed on the roots of wetland
      plants and their rhizospheres create environmental conditions favorable for iron
      reducing bacteria that promote the in situ immobilization of uranium. Greenhouse
      microcosm studies were conducted using native plants (Sparganium americanum) from
      a wetland located on the Savannah River Site, Aiken, SC. After iron plaques were
      established during a 73-day period by using an anoxic Fe(II)-rich nutrient
      solution, a U(VI) amended nutrient solution was added to the system for an
      additional two months. Compared to plant-free control microcosms, microcosms
      containing iron plaques successfully stimulated the growth of targeted iron
      reducing bacteria, Geobacter spp. Their population continuously increased after
      the introduction of the U(VI) nutrient solution. The reduction of some of the
      U(VI) to U(IV) by iron reducing bacteria was deduced based on the observations
      that the aqueous Fe(II) concentrations increased while the U(VI) concentrations
      decreased. The Fe(II) produced by the iron reducing bacteria was assumed to be
      reoxidized by the oxygen released from the roots. Advanced spectroscopic analyses
      revealed that a significant fraction of the U(VI) had been reduced to U(IV) and
      they were commonly deposited in association with phosphorus on the iron plaque. 

PMID- 25051144
TI  - MRI of axillary brachial plexus blocks: a randomised controlled study.
AB  - BACKGROUND: Axillary plexus blocks are usually guided by ultrasound, but
      alternative methods may be used when ultrasound equipment is lacking. For a
      nonultrasound-guided axillary block, the need for three injections has been
      questioned. OBJECTIVES: Could differences in block success between single, double
      and triple deposits methods be explained by differences in local anaesthetic
      distribution as observed by MRI? DESIGN: A blinded and randomised controlled
      study. SETTING: Conducted at Oslo University Hospital, Rikshospitalet, Norway
      from 2009 to 2011. PATIENTS: Forty-five ASA 1 to 2 patients scheduled for surgery
      were randomised to three equally sized groups. All patients completed the study.
      INTERVENTIONS: Patients in the single-deposit group had an injection through a
      catheter parallel to the median nerve. In the double-deposit group the patients
      received a transarterial block. In the triple-deposit group the injections of the
      two other groups were combined. Upon completion of local anaesthetic injection
      the patients were scanned by MRI, before clinical block assessment. The
      distribution of local anaesthetic was scored by its closeness to terminal nerves
      and cords of the brachial plexus, as seen by MRI. The clinical effect was scored
      by the degree of sensory block in terminal nerve innervation areas. MAIN OUTCOME
      MEASURES: Sensory block effect and MRI distribution pattern. RESULTS: The triple
      deposit method had a higher success rate (100%) than the single-deposit method
      (67%) and the double-deposit method (67%) in blocking all cutaneous nerves distal
      to the elbow (P = 0.04). The patients in the triple-deposit group most often had
      the best MRI scores. For any nerve or cord, at least one of the single-deposit or
      double-deposit groups had a similarly high MRI score as the triple-deposit group.
      CONCLUSION: Distal to the elbow, the triple-deposit method had the highest
      sensory block success rate. This could be explained to some extent by analysis of
      the magnetic resonance images. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01033006.

PMID- 25051145
TI  - How to tell a wife from a hat: affective feedback in perceptual categorization.
AB  - How do people understand that their perception is correct? In line with the
      recurring idea of perception as prediction, the affective feedback account of
      hypotheses testing suggests that correct perceptual predictions are reinforced
      with positive affect. In four experiments, we tested whether correct
      categorization of a degraded image will lead to more positive liking ratings. The
      obtained findings supported the proposed approach: subjects liked the images they
      were able to perceive correctly more than others. Importantly, these findings
      were independent of the initial affective valence of stimuli. A further
      investigation demonstrated that this effect exists only when answers are at least
      moderately confident. The obtained findings add to the growing amount of
      literature on the role of affect in basic cognitive processing. 

PMID- 25051146
TI  - Role of the Pepino mosaic virus 3'-untranslated region elements in negative
      strand RNA synthesis in vitro.
AB  - Pepino mosaic virus (PepMV) is a mechanically-transmitted positive-strand RNA
      potexvirus, with a 6410 nt long single-stranded (ss) RNA genome flanked by a 5'
      methylguanosine cap and a 3' poly-A tail. Computer-assisted folding of the 64 nt
      long PepMV 3'-untranslated region (UTR) resulted in the prediction of three stem
      loop structures (hp1, hp2, and hp3 in the 3'-5' direction). The importance of
      these structures and/or sequences for promotion of negative-strand RNA synthesis
      and binding to the RNA dependent RNA polymerase (RdRp) was tested in vitro using
      a specific RdRp assay. Hp1, which is highly variable among different PepMV
      isolates, appeared dispensable for negative-strand synthesis. Hp2, which is
      characterized by a large U-rich loop, tolerated base-pair changes in its stem as
      long as they maintained the stem integrity but was very sensitive to changes in
      the U-rich loop. Hp3, which harbours the conserved potexvirus ACUUAA hexamer
      motif, was essential for template activity. Template-RNA polymerase binding
      competition experiments showed that the ACUUAA sequence represents a high
      affinity RdRp binding element.

PMID- 25051147
TI  - Complete genome sequences of new divergent potato virus X isolates and
      discrimination between strains in a mixed infection using small RNAs sequencing
      approach.
AB  - Potato virus X (PVX; genus Potexvirus, family Alphaflexiviridae, order
      Tymovirales) is one of the most widespread and intensively studied viruses of
      potato. However, little is known about its diversity in its likely center of
      radiation, the Andean region of South America. To fill this gap, the strategy of
      Illumina deep sequencing of small RNAs was used to obtain complete or near
      complete genome sequence of PVX from 5 symptomatically infected greenhouse and 3
      field samples (Solanum tuberosum) from Peru. PVX sequences determined in this
      study were assigned into three different phylogenetic groups of isolates.
      Notably, a complete genome sequence of a representative of a new PVX phylogenetic
      lineage was obtained, which shows a high level of sequence dissimilarity to other
      completely sequenced isolates (~17%). The new PVX genotype was detected in
      greenhouse and field samples. One of the field samples was infected with the
      mixture of two PVX strains, which were efficiently discriminated using small RNA
      sequencing approach. The study confirms the utility of small RNAs deep sequencing
      for successful viral strain differentiation and discovery of new viral strains
      and indicates a high diversity of PVX in the Andean region of South America, a
      pattern which may be expected also for other potato pathogens. 

PMID- 25051148
TI  - Nucleotide excision repair gene ERCC1 19007T>C polymorphism contributes to lung
      cancer susceptibility: a meta-analysis.
AB  - AIMS: Association studies of ERCC1 19007T>C polymorphism and lung cancer have
      yielded inconsistent results, possibly because single studies often lack
      sufficient statistical power. METHODS: We examined the association by performing
      a meta-analysis. Two investigators independently searched the Google Scholar,
      PubMed, and CNKI Databases. Summary odds ratios (ORs) and 95% confidence
      intervals (95% CIs) for 19007T>C polymorphism and lung cancer were calculated in
      a fixed-effects model and a random-effects model, when appropriate. Publication
      bias was evaluated using Begg's funnel plot. RESULTS: Overall, the meta-analysis
      included 7 case-control studies for each polymorphism with 3840 confirmed lung
      cancer cases and 4712 healthy controls in total. Meta-analysis results showed a
      significant association between 19007T>C polymorphism and lung cancer risk (CC
      vs. TT: OR=0.72, 95% CI 0.53-0.99; CT vs. TT: OR=0.84, 95% CI 0.73-0.98; Dominant
      model: OR=0.70, 95% CI 0.52-0.95). Further stratified analyses conducted by
      ethnicity reveal a statistically significant association in Asians (Dominant
      model: OR=0.63, 95% CI 0.43-0.93), but no significant association in Europeans.
      CONCLUSIONS: This meta-analysis suggests that the ERCC1 19007T>C polymorphism may
      be associated with lung cancer risk in Asians, while larger scale association
      studies are necessary to further validate the association of 19007T>C
      polymorphism with lung cancer risk.

PMID- 25051149
TI  - Asymmetric Friedel-Crafts reactions of N-tert-butylsulfinyl-3,3,3
      trifluoroacetaldimines: general access to enantiomerically pure indoles
      containing a 1-amino-2,2,2-trifluoroethyl group.
AB  - We have demonstrated that 3,3,3-trifluoroacetaldimine (S)-1 easily reacts with
      indole derivatives under Friedel-Crafts reactions to provide reliable and
      generalized access to biologically interesting compounds containing the
      CF3CH(NH2)- pharmacophoric group. The reactions proceed with high rates and
      generally excellent yields (>90%) and stereochemical outcomes (99:1 dr). 

PMID- 25051150
TI  - Mechanical response of human abdominal walls ex vivo: Effect of an incisional
      hernia and a mesh repair.
AB  - The design of meshes for the treatment of incisional hernias could benefit from
      better knowledge of the mechanical response of the abdominal wall and how this
      response is affected by the implant. The aim of this study was to characterise
      the mechanical behaviour of the human abdominal wall. Abdominal walls were tested
      ex vivo in three states: intact, after creation of a defect simulating an
      incisional hernia, and after reparation with a mesh implanted intraperitonally.
      For each state, the abdominal wall was subjected to air pressure loading. Local
      strain fields were determined using digital image correlation techniques. The
      strain fields on the internal and external surfaces of the abdominal wall
      exhibited different patterns. The strain patterns on the internal surface
      appeared to be related to the underlying anatomy of the abdominal wall. Higher
      strains were observed along the linea alba than along the perpendicular
      direction. Under pressure loading, the created incision increased the strain of
      the abdominal wall compared to the intact state in 5 cases of a total 6. In
      addition, the mesh repair decreased the strains of the abdominal wall compared to
      the incised state in 4 cases of 6. These results suggest that the intraperitoneal
      mesh restores at least partially the mechanical behaviour of the wall and
      provides quantification of the effects on the strains in various regions. 

PMID- 25051151
TI  - Identification of anisotropic tensile strength of cortical bone using Brazilian
      test.
AB  - For a proper analysis of cortical bone behaviour, it is essential to take into
      account both the elastic stiffness and the failure criteria. While ultrasound
      methods allow complete identification of the elastic orthotropic coefficients,
      tests used to characterise the various failure mechanisms and to identify the
      brittle tensile strength in all directions are currently inadequate. In the
      present work we propose the Brazilian test as a complement to conventional
      tensile tests. In fact, this experimental technique, rarely employed in the
      biomechanics field, has the potential to provide an accurate description of the
      anisotropic strength of cortical bone. Additionally, it allows us to assess the
      scale influence on failure behaviour which may be attributed to an intrinsic
      length in correlation with the cortical bone microstructure. In order to
      correctly set up the Brazilian test, several aspects such as the machining, the
      geometrical parameters of the specimen and the loading conditions were
      determined. The finite element method was used to evaluate the maximal tensile
      stress at the centre of a 2D anisotropic elastic specimen as a simple function of
      the loading. To validate the protocol, the Brazilian test was carried out on 29
      cortical bovine cylindrical specimens with diameters ranging from 10mm to 4mm. 

PMID- 25051152
TI  - In situ osteoblast mineralization mediates post-injection mechanical properties
      of osteoconductive material.
AB  - The objective of this study was to understand the temporal relationship between
      in situ generated calcium content (mineralization) and the mechanical properties
      of an injectable orthobiologic bone-filler material. Murine derived osteoblast
      progenitor cells were differentiated using osteogenic factors and encapsulated
      within an injectable polycaprolactone nanofiber-collagen composite scaffold (PN
      COL +osteo) to evaluate the effect of mineralization on the mechanical properties
      of the PN-COL scaffold. A comprehensive study was conducted using both an
      experimental and a predictive analytical mechanical analysis for mechanical
      property assessment as well as an extensive in vitro biological analysis for in
      situ mineralization. Cell proliferation was evaluated using a PicoGreen dsDNA
      quantification assay and in situ mineralization was analyzed using both an
      alkaline phosphatase (ALP) assay and an Alizarin Red stain-based assay.
      Mineralized matrix formation was further evaluated using energy dispersive x-ray
      spectroscopy (EDS) and visualized using SEM and histological analyses.
      Compressive mechanical properties of the PN-COL scaffolds were determined using a
      confined compression stress-relaxation protocol and the obtained data was fit to
      the standard linear solid viscoelastic material mathematical model to demonstrate
      a relationship between increased in situ mineralization and the mechanical
      properties of the PN-COL scaffold. Cell proliferation was constant over the 21
      day period. ALP activity and calcium concentration significantly increased at day
      14 and 21 as compared to PN-COL -osteo with undifferentiated osteoblast
      progenitor cells. Furthermore, at day 21 EDS, SEM and von Kossa histological
      staining confirmed mineralized matrix formation within the PN-COL scaffolds.
      After 21 days, compressive modulus, peak stress, and equilibrium stress
      demonstrate significant increases of 3.4-fold, 3.3-fold, and 4.0-fold
      respectively due to in situ mineralization. Viscoelastic parameters calculated
      through the standard linear solid mathematical model fit to the stress-relaxation
      data also indicate improved mechanical properties after in situ mineralization.
      This investigation clearly demonstrates that in situ mineralization can increase
      the mechanical properties of an injectable orthobiologic scaffold and can
      possibly guide the design of an effective osteoconductive injectable material. 

PMID- 25051154
TI  - Modulating the band gap of germanane nanoribbons for quantum well devices.
AB  - The effective modulation of the band gaps in nanostructures is of both
      fundamental and technological interest because a tunable band gap gives great
      flexibility in the design and optimization of nanodevices. Using density
      functional theory calculations, we have shown that germanane nanoribbons of
      various widths or under various strains can provide rich band gaps. Width- and
      strain-induced changes in the band gaps of germanane nanoribbons result from a
      reduction in quantum confinement with width and the weakening of sp(3)
      hybridization with strain, respectively. Both changes represent a monotonous
      relationship. To utilize such a monotonous change in band gap, we designed a
      quantum well based on germanane nanoribbons in which photoexcited electrons and
      holes occupy the same spatial region, resulting in a desirable light-emitting
      device. 

PMID- 25051153
TI  - Plant microRNA-target interaction identification model based on the integration
      of prediction tools and support vector machine.
AB  - BACKGROUND: Confident identification of microRNA-target interactions is
      significant for studying the function of microRNA (miRNA). Although some
      computational miRNA target prediction methods have been proposed for plants,
      results of various methods tend to be inconsistent and usually lead to more false
      positive. To address these issues, we developed an integrated model for
      identifying plant miRNA-target interactions. RESULTS: Three online miRNA target
      prediction toolkits and machine learning algorithms were integrated to identify
      and analyze Arabidopsis thaliana miRNA-target interactions. Principle component
      analysis (PCA) feature extraction and self-training technology were introduced to
      improve the performance. Results showed that the proposed model outperformed the
      previously existing methods. The results were validated by using degradome
      sequencing supported Arabidopsis thaliana miRNA-target interactions. The proposed
      model constructed on Arabidopsis thaliana was run over Oryza sativa and Vitis
      vinifera to demonstrate that our model is effective for other plant species.
      CONCLUSIONS: The integrated model of online predictors and local PCA-SVM
      classifier gained credible and high quality miRNA-target interactions. The
      supervised learning algorithm of PCA-SVM classifier was employed in plant miRNA
      target identification for the first time. Its performance can be substantially
      improved if more experimentally proved training samples are provided.

PMID- 25051155
TI  - Synthesis of U3Se5 and U3Te5 type polymorphs of Ta3N5 by combining high pressure
      temperature pathways with a chemical precursor approach.
AB  - Combining metastable precursors with high pressure-temperature treatment is a
      powerful tool to make nitrogen-rich metal nitrides. Two new dense polymorphs of
      Ta3N5 have previously been theoretically predicted, with U3Se5 (Pnma) and U3Te5
      (Pnma) structure types, and are now shown to exist. Amorphous Ta3N5 from thermal
      ammonolysis of an amorphous polymeric precursor was laser heated at 22 GPa and
      examined using synchrotron X-ray diffraction to reveal the emergence of these two
      novel polymorphs. 

PMID- 25051156
TI  - Cardiovascular responses to microinjections of endomorphin-2 into the nucleus of
      the solitary tract are attenuated in the spontaneously hypertensive rat.
AB  - Stimulation of u1-opioid receptors (M1ORs) in the medial nucleus solitarius
      (mNTS) by endomorphin-2 (EM2) elicits decreases in mean arterial pressure (MAP),
      heart rate (HR) and greater splanchnic nerve activity (GSNA) in Wistar rats. We
      tested the hypothesis that EM2-induced responses in the mNTS may be attenuated in
      the spontaneously hypertensive rat (SHR). Experiments were carried out in
      urethane-anesthetized, artificially ventilated, adult male SHR and Wistar-Kyoto
      rats (WKY). Alterations in responses to chemical stimulation of the hypothalamic
      arcuate nucleus (ARCN) after bilateral blockade of M1ORs in the mNTS were also
      studied. In SHR, microinjections of EM2 into the mNTS elicited smaller decreases
      in MAP, HR and GSNA compared to those elicited in WKY; smaller cardiovascular
      responses in SHR can be explained by lower expression of M1OR mRNA in the NTS of
      SHR compared to WKY. Decreases in MAP and GSNA and increases in HR were elicited
      by microinjections of N-methyl-D-aspartic acid (NMDA) into the ARCN of WKY.
      Bilateral blockade of M1ORs in the mNTS attenuated the decreases in MAP and GSNA
      and exaggerated the increases in HR elicited by the ARCN stimulation in WKY but
      not in SHR. Tonic inhibitory activity of neuropeptide Y/gamma-aminobutyric acid
      (NPY/GABA) neurons in the ARCN is attenuated in SHR; this observation may explain
      increases in MAP, GSNA and HR elicited by microinjections of NMDA into the ARCN
      of SHR. These results demonstrate that attenuation of EM2-induced responses in
      the mNTS of SHR may contribute to the excitatory responses elicited by ARCN
      stimulation in SHR.

PMID- 25051157
TI  - microRNA response element-regulated TIKI2 expression suppresses the tumorigencity
      of malignant gliomas.
AB  - Glioma is the most common brain malignancy and has a very poor prognosis. The
      current treatment options have a minimal benefit on prolonging patient survival
      time. Accumulating data have shown that the WNT signaling pathway has a critical
      function in the progression and invasion of glioma. Thus, targeting WNT signaling
      appears to be an effective anti-glioma strategy. TIKI2 was recently found to
      suppress the activation of the WNT signaling pathway by post-translationally
      modifying secreted WNT proteins. The implication of TIKI2 aberrance in cancers
      and its potential therapeutic effect, however, has not been studied. In the
      present study, a glioma-specific adenoviral vector was constructed, which was
      regulated by response elements of miR-124, to express TIKI2 in glioma cells (Ad
      TIKI2-124). Ad-TIKI2-124 was found to potently suppress the activation of WNT
      signaling in glioma cells. This inhibitory effect on the WNT signaling pathway
      lead to the reduction in proliferation, colony formation ability and invasion of
      glioma cell lines. In addition, animal experiments confirmed that the expression
      of the Ad-TIKI2-124 construct could compromise the tumorigenicity of glioma cells
      in vivo. Furthermore, this glioma-selective TIKI2 expression protected normal
      cells from toxicity. In conclusion, the present study demonstrated that
      adenovirus-mediated TIKI2 therapy may be used for glioma treatment and therefore
      warrants further clinical studies.

PMID- 25051158
TI  - Optically active metasurface with non-chiral plasmonic nanoantennas.
AB  - We design, fabricate, and experimentally demonstrate an optically active
      metasurface of lambda/50 thickness that rotates linearly polarized light by 45
      degrees  over a broadband wavelength range in the near IR region. The rotation is
      achieved through the use of a planar array of plasmonic nanoantennas, which
      generates a fixed phase-shift between the left circular polarized and right
      circular polarized components of the incident light. Our approach is built on a
      new supercell metasurface design methodology: by judiciously designing the
      location and orientation of individual antennas in the structural supercells, we
      achieve an effective chiral metasurface through a collective operation of
      nonchiral antennas. This approach simplifies the overall structure when compared
      to designs with chiral antennas and also enables a chiral effect which
      quantitatively depends solely on the supercell geometry. This allows for greater
      tolerance against fabrication and temperature effects. 

PMID- 25051159
TI  - Physicochemical and functional characterization of the collagen
      polyvinylpyrrolidone copolymer.
AB  - Collagen-polyvinylpyrrolidone (C-PVP) is a copolymer that is generated from the
      gamma irradiation of a mixture of type I collagen and low-molecular-weight PVP.
      It is characterized by immunomodulatory, fibrolytic, and antifibrotic properties.
      Here, we used various physicochemical and biological strategies to characterize
      the structure, biochemical susceptibility, as well as its effects on metabolic
      activity in fibroblasts. C-PVP contained 16 times more PVP than collagen, but
      only 55.8% of PVP was bonded. Nevertheless, the remaining PVP exerted strong
      structural activity due to the existence of weak bonds that provided shielding in
      the NMR spectra. On SEM and AFM, freeze-dried C-PVP appeared as a film that
      uniformly covered the collagen fibers. Size analysis revealed the presence of
      abundant PVP molecules in the solution of the copolymer with a unique dimension
      related to macromolecular combinations. Calorimetric analysis showed that the
      copolymer in solution exhibited structural changes at 110  degrees C, whereas the
      lyophilized form showed such changes at temperatures below 50  degrees C. The
      copolymer presented a rheopectic behavior, with a predominant effect of the
      collagen. C-PVP had biological effects on the expression of integrin alpha2 and
      prolyl-hydroxylase but did not interact with cells through the collagen receptors
      because it did not inhibit or slow contraction. 

PMID- 25051160
TI  - Home-based HIV testing for men who have sex with men in China: a novel community
      based partnership to complement government programs.
AB  - BACKGROUND: The coverage of HIV testing among Chinese men who have sex with men
      (MSM) remains low after the scale-up of free HIV testing at government-sponsored
      testing sites. We evaluated the feasibility of home-based HIV self-testing and
      the willingness to be HIV tested at community-based organizations (CBO). METHODS:
      We recruited MSM via on-line advertisement, where they completed an on-line
      informed consent and subsequent questionnaire survey. Eligible MSM received HIV
      rapid testing kits by mail, performed the test themselves and reported the result
      remotely. RESULTS: Of the 220 men taking a home-based HIV self-testing, 33 MSM
      (15%) were seropositive. Nearly 65% of the men reported that they were willing to
      take HIV testing at CBO, while 28% preferred receiving free HIV testing in the
      government programs at local Centers for Disease Control and Prevention (CDC).
      Older and lower-income MSM, those who self-reported homosexual orientation, men
      with no history of sexually transmitted diseases and a lower number of sexual
      partners in the past six months were associated with preference for taking HIV
      testing at CBOs. The top three self-reported existing barriers for HIV testing
      were: no perception of HIV risk (56%), fear of an HIV positive result being
      reported to the government (41%), and fear of a positive HIV test result (36%).
      CONCLUSION: Home-based HIV self-testing is an alternative approach for increasing
      the coverage of HIV testing among Chinese MSM. CBO-based HIV testing is a
      potential alternative, but further studies are needed to evaluate its
      feasibility.

PMID- 25051161
TI  - Early postnatal EEG features of perinatal arterial ischaemic stroke with
      seizures.
AB  - BACKGROUND: Stroke is the second most common cause of seizures in term neonates
      and is associated with abnormal long-term neurodevelopmental outcome in some
      cases. OBJECTIVE: To aid diagnosis earlier in the postnatal period, our aim was
      to describe the characteristic EEG patterns in term neonates with perinatal
      arterial ischaemic stroke (PAIS) seizures. DESIGN: Retrospective observational
      study. PATIENTS: Neonates >37 weeks born between 2003 and 2011 in two hospitals.
      METHOD: Continuous multichannel video-EEG was used to analyze the background
      patterns and characteristics of seizures. Each EEG was assessed for continuity,
      symmetry, characteristic features and sleep cycling; morphology of electrographic
      seizures was also examined. Each seizure was categorized as electrographic-only
      or electroclinical; the percentage of seizure events for each seizure type was
      also summarized. RESULTS: Nine neonates with PAIS seizures and EEG monitoring
      were identified. While EEG continuity was present in all cases, the background
      pattern showed suppression over the infarcted side; this was quite marked (>50%
      amplitude reduction) when the lesion was large. Characteristic unilateral bursts
      of theta activity with sharp or spike waves intermixed were seen in all cases.
      Sleep cycling was generally present but was more disturbed over the infarcted
      side. Seizures demonstrated a characteristic pattern; focal sharp waves/spike
      polyspikes were seen at frequency of 1-2 Hz and phase reversal over the central
      region was common. Electrographic-only seizure events were more frequent compared
      to electroclinical seizure events (78 vs 22%). CONCLUSIONS: Focal electrographic
      and electroclinical seizures with ipsilateral suppression of the background
      activity and focal sharp waves are strong indicators of PAIS. Approximately 80%
      of seizure events were the result of clinically unsuspected seizures in neonates
      with PAIS. Prolonged and continuous multichannel video-EEG monitoring is
      advocated for adequate seizure surveillance.

PMID- 25051162
TI  - The effect of substrate competition on the metabolism of polyphosphate
      accumulating organisms (PAOs).
AB  - The type of carbon source present in the wastewater is one factor that affects
      the competition between polyphosphate accumulating organisms (PAO) and glycogen
      accumulating organisms (GAO) and therefore, the efficiency of the enhanced
      biological phosphorus removal (EBPR) process. This study investigated the impact
      of the carbon source composition on the anaerobic and aerobic kinetics of PAOs
      and the EBPR performance of an 85% PAO enrichment. When both acetate (HAc) and
      propionate (HPr) were present, propionate was depleted more quickly, with a
      constant uptake rate of 0.18 +/- 0.02 C-mol/(C-mol biomass.h), while the acetate
      uptake rate decreased with an increase in propionate concentration, due to the
      substrate competition between acetate and propionate. The metabolic model for
      PAOs was modified to incorporate the anaerobic substrate competition effect. The
      aerobic rates for phosphorus (P) uptake, glycogen production and
      polyhydroxyalkanoates (PHA) degradation were within the same range for all tests,
      indicating that these rates are essentially independent of the acetate and
      propionate concentration, simplifying the calibration procedure for metabolic
      models. The metabolic model applied to describe the anaerobic and aerobic
      activity agreed well with the experimental data of HAc, HPr, P, PHA and biomass
      growth. The low glycogen consumption observed suggest that some reducing
      equivalents were generated anaerobically through the TCA cycle. The results of
      this work suggest that the propionate uptake kinetics by PAOs can provide them an
      advantage over GAOs in EBPR systems, even when the propionate fraction of the
      influent is relatively low. 

PMID- 25051164
TI  - Ectopic cortical anaplastic ependymoma: an unusual case report and literature
      review.
AB  - Ependymona occasionally occurs outside the ventricular structures, which is
      called ectopic ependymona (EE), while pure cortex location is uncommon. However,
      cortical anaplastic ependymoma (CE) is rare, especially in children. There were
      only four primary CEs, which is located in the superficial cortex, were reported
      the age of the patient under 12 years old. The present case is a 20-month-old boy
      presenting with simple partial seizure was treated in our department. Cranial
      magnetic resonance imaging (MRI) revealed a fronto-parietal lobe mass of more
      than 50mm in diameter with mixed signal intensity. Total removal of the mass
      lesion was performed without any neurological deficit. Pathological examination
      of the excised tumor were consistent with anaplastic ependymoma (AE). The patient
      had a good recovery after his surgical resection. Radiotherapy and chemotherapy
      were not taken into account in view of his age, the favorable site and the
      complete resection. The management of this unusual tumor is summarized in this
      paper. 

PMID- 25051165
TI  - Spinal tuberculosis at the posterior element of spinal column: case report.

PMID- 25051163
TI  - Insular and hippocampal gray matter volume reductions in patients with major
      depressive disorder.
AB  - BACKGROUND: Major depressive disorder is a serious psychiatric illness with a
      highly variable and heterogeneous clinical course. Due to the lack of consistent
      data from previous studies, the study of morphometric changes in major depressive
      disorder is still a major point of research requiring additional studies. The aim
      of the study presented here was to characterize and quantify regional gray matter
      abnormalities in a large sample of clinically well-characterized patients with
      major depressive disorder. METHODS: For this study one-hundred thirty two
      patients with major depressive disorder and 132 age- and gender-matched healthy
      control participants were included, 35 with their first episode and 97 with
      recurrent depression. To analyse gray matter abnormalities, voxel-based
      morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain
      analyses as well as a region-of-interest approach on the hippocampal formation,
      anterior cingulate cortex and amygdala, correlating the number of depressive
      episodes. RESULTS: Compared to healthy control persons, patients showed a strong
      gray-matter reduction in the right anterior insula. In addition, region-of
      interest analyses revealed significant gray-matter reductions in the hippocampal
      formation. The observed alterations were more severe in patients with recurrent
      depressive episodes than in patients with a first episode. The number of
      depressive episodes was negatively correlated with gray-matter volume in the
      right hippocampus and right amygdala. CONCLUSIONS: The anterior insula gray
      matter structure appears to be strongly affected in major depressive disorder and
      might play an important role in the neurobiology of depression. The hippocampal
      and amygdala volume loss cumulating with the number of episodes might be
      explained either by repeated neurotoxic stress or alternatively by higher relapse
      rates in patients showing hippocampal atrophy.

PMID- 25051166
TI  - Visualization of small veins with susceptibility-weighted imaging for
      stereotactic trajectory planning in deep brain stimulation.
AB  - Intracerebral hemorrhage (ICH) is the most significant complication of Deep Brain
      Stimulation (DBS). To prevent ICH, stereotactic contrast enhanced T1-weighted
      images are used to visualize vessels as source of hemorrhage. Susceptibility
      Weighted Imaging (SWI) is an MRI sequence with improved visualization of
      susceptibility differences between tissues, particularly sensitive for brain
      veins. The aim of this prospective study was to analyze the utility of SWI
      compared to contrast enhanced stereotactic T1-weighted images for trajectory
      planning of DBS. Preoperative SWI was performed in 33 patients undergoing DBS and
      was compared to the T1-weighted images. Vessels identified only with SWI in
      relation to the bilateral planned trajectory were analyzed. In all patients
      vessels were depicted on SWI only within the planned trajectory (range 1-4
      vessels, for each trajectory, mean: 2.4). In 6 patients vessels were identified
      on SWI adjacent to the target (up to 5mm distal from target). In 11 patients SWI
      visualized additional cortical veins adjacent to the entry point of the
      trajectory. The apparent diameter of these vessels ranged between 0.8 and 2.1mm
      (mean: 1.2mm). Postoperative MRI was compared with preoperative SWI and revealed
      in two patients small (<3 mm) T2 hyperintense lesions along electrodes without
      correlation with visualized veins. SWI facilitates the visualization of small
      veins superior to T1-weighted images. However, cerebral veins within the
      trajectory were not found to be a significant source of ICH after DBS. Potential
      sources of ICH are mesencephal veins at the endpoint of electrodes which can
      cause fatal hemorrhage and are visualized with SWI reliably.

PMID- 25051167
TI  - Quality of life in advanced Parkinson's disease after bilateral subthalamic
      stimulation: 2 years follow-up study.
AB  - OBJECTIVE: The aims of this study were to assess the quality of life (QoL) using
      Parkinson's Disease Questionnaire PDQ-39 after bilateral subthalamic deep brain
      stimulation (STN DBS), and to identify correlations between changes in UPDRS
      score and separate PDQ-39 QoL dimensions and PDQ summary index (SI) score at long
      term follow-up. METHODS: We evaluated 16 patients with advanced PD after
      bilateral STN DBS. All 16 patients were assessed 1 year after surgery and 14 were
      studied 2 years after surgery. The patients were assessed using Unified
      Parkinson's Disease Rating Scale (UPDRS) in medication-on and medication-off
      conditions, both preoperatively and postoperatively. All UPDRS evaluations were
      performed postoperatively during stimulation-on condition. QoL levels were
      determined by applying PDQ-39 questionnaire. RESULTS: The UPDRS scores after 1
      and 2 years in medication-off and -on conditions when bilateral STN DBS was
      switched on showed a significant difference between baseline scores and follow-up
      scores (both in -off and -on conditions) in every UPDRS measurement except for
      mentation after 2 years. Most of P-values indicated that the differences were
      highly significant (P<0.01) based on Wilcoxon signed-rank test. All dimensions of
      PDQ-39 as well PDQ-39 SI score were highly significantly improved after 1 year.
      The same improvements were visible in 2 years follow-up with the exception of
      social support and communication. We found a positive correlation between ADL
      UPDRS, motor off UPDRS scores and PDQ-39 ADL and PDQ-39 SI scores. A further
      analysis of separate motor PD features revealed that tremor, bradykinesia and
      axial features were correlated with improvements mostly seen in PDQ-39 ADL and
      PDQ-39 SI scores. Moreover, in medication-on condition, we found a strong
      correlation between dyskinesia UPDRS score and PDQ-39 mobility, ADL, and PDQ-39
      SI score. We observed a negative correlation between improved fluctuation UPDRS
      score and PDQ-39 mobility. We identified no correlation between the duration of
      the off period and levodopa dose and changes in PDQ-39. CONCLUSION: STN DBS
      significantly improved important aspects of QoL as measured by PDQ-39. The
      improvements were maintained at 2 years follow-up except for social support and
      communication. We demonstrated a positive correlation between changes in the off
      condition of motor UPDRS scores and dyskinesia UPDRS scores in several PDQ-39
      dimensions, whereas fluctuation UPDRS scores were negatively correlated with PDQ
      39 mobility scores.

PMID- 25051168
TI  - Ginseng diminishes lung disease in mice immunized with formalin-inactivated
      respiratory syncytial virus after challenge by modulating host immune responses.
AB  - Formalin-inactivated respiratory syncytial virus (FI-RSV) immunization is known
      to cause severe pulmonary inflammatory disease after subsequent RSV infection.
      Ginseng has been used in humans for thousands of years due to its potential
      health benefits. We investigated whether ginseng would have immune modulating
      effects on RSV infection in mice previously immunized with FI-RSV. Oral
      administration of mice with ginseng increased IgG2a isotype antibody responses to
      FI-RSV immunization, indicating T-helper type 1 (Th1) immune responses. Ginseng
      treated mice that were nonimmunized or previously immunized with FI-RSV showed
      improved protection against RSV challenge compared with control mice without
      ginseng treatment. Ginseng-mediated improved clinical outcomes after live RSV
      infection were evidenced by diminished weight losses, decreased interleukin-4
      cytokine production but increased interferon-gamma production, modulation of CD3
      T-cell populations toward a Th1 response, and reduced inflammatory response.
      Ginseng-mediated protective host immune modulation against RSV pulmonary
      inflammation was observed in different strains of wild-type and mutant mice.
      These results indicate that ginseng can modulate host immune responses to FI-RSV
      immunization and RSV infection, resulting in protective effects against pulmonary
      inflammatory disease. 

PMID- 25051169
TI  - Selection mosaic exerted by specialist and generalist herbivores on chemical and
      physical defense of Datura stramonium.
AB  - Selection exerted by herbivores is a major force driving the evolution of plant
      defensive characters such as leaf trichomes or secondary metabolites. However,
      plant defense expression is highly variable among populations and identifying the
      sources of this variation remains a major challenge. Plant populations are often
      distributed across broad geographic ranges and are exposed to different herbivore
      communities, ranging from generalists (that feed on diverse plant species) to
      specialists (that feed on a restricted group of plants). We studied eight
      populations of the plant Datura stramonium usually eaten by specialist or
      generalist herbivores, in order to examine whether the pattern of phenotypic
      selection on secondary compounds (atropine and scopolamine) and a physical
      defense (trichome density) can explain geographic variation in these traits.
      Following co-evolutionary theory, we evaluated whether a more derived alkaloid
      (scopolamine) confers higher fitness benefits than its precursor (atropine), and
      whether this effect differs between specialist and generalist herbivores. Our
      results showed consistent directional selection in almost all populations and
      herbivores to reduce the concentration of atropine. The most derived alkaloid
      (scopolamine) was favored in only one of the populations, which is dominated by a
      generalist herbivore. In general, the patterns of selection support the existence
      of a selection mosaic and accounts for the positive correlation observed between
      atropine concentration and plant damage by herbivores recorded in previous
      studies. 

PMID- 25051170
TI  - Minireview: Steroid-regulated paracrine mechanisms controlling implantation.
AB  - Implantation is an essential process during establishment of pregnancy in
      mammals. It is initiated with the attachment of the blastocyst to a receptive
      uterine epithelium followed by its invasion into the stromal tissue. These events
      are profoundly regulated by the steroid hormones 17beta-estradiol and
      progesterone. During the past several years, mouse models harboring conditional
      gene knockout mutations have become powerful tools for determining the functional
      roles of cellular factors involved in various aspects of implantation biology.
      Studies using these genetic models as well as primary cultures of human
      endometrial cells have established that the estrogen receptor alpha, the
      progesterone receptor, and their downstream target genes critically regulate
      uterine growth and differentiation, which in turn control embryo-endometrial
      interactions during early pregnancy. These studies have uncovered a diverse array
      of molecular cues, which are produced under the influence of estrogen receptor
      alpha and progesterone receptor and exchanged between the epithelial and stromal
      compartments of the uterus during the progressive phases of implantation. These
      paracrine signals are critical for acquisition of uterine receptivity and
      functional interactions with the embryo. This review highlights recent work
      describing paracrine mechanisms that govern steroid-regulated uterine epithelial
      stromal dialogue during implantation and their roles in fertility and disease. 

PMID- 25051171
TI  - Melanocortin 3 receptor has a 5' exon that directs translation of apically
      localized protein from the second in-frame ATG.
AB  - Melanocortin-3 receptor (MC3R) is a canonical MSH receptor that plays an
      essential role in energy homeostasis. Variants in MC3R have been implicated in
      obesity in humans and mice. However, interpretation of the functional
      consequences of these variants is challenging because the translational start
      site of MC3R is unclear. Using 5' rapid amplification of cDNA ends, we discovered
      a novel upstream exon that extends the length of the 5' untranslated region (UTR)
      in MC3R without changing the open-reading frame. The full-length 5' UTR directs
      utilization of an evolutionarily conserved second in-frame ATG as the primary
      translation start site. MC3R synthesized from the second ATG is localized to
      apical membranes of polarized Madin-Darby canine kidney cells, consistent with
      its function as a cell surface mediator of melanocortin signaling. Expression of
      MC3R causes relocalization of melanocortin receptor accessory protein 2, an
      accessory factor for melanocortin-2 receptor, to the apical membrane, coincident
      with the location of MC3R. In contrast, protein synthesized from MC3R cDNAs
      lacking the 5' UTR displayed diffuse cytosolic distribution and has no effect on
      the distribution of melanocortin receptor accessory protein 2. Our findings
      demonstrate that a previously unannotated 5' exon directs translation of MC3R
      protein that localizes to apical membranes of polarized cells. Together, our work
      provides insight on the structure of human MC3R and reveals a new pathway for
      regulation of energy metabolism. 

PMID- 25051172
TI  - Transient estrogen receptor binding and p300 redistribution support a squelching
      mechanism for estradiol-repressed genes.
AB  - Proper gene regulation is essential for proper organismal development and
      appropriate responses to external stimuli. Specialized factors, termed master
      regulators, are often responsible for orchestrating the molecular events that
      result from signaling cascades. Master regulators coordinate the activation and
      repression of specific gene classes. Estrogen receptor alpha (ER) precipitates
      the signaling cascade that results from endogenous or exogenous estrogen
      hormones. ER is a classic transcriptional activator and the mechanisms by which
      ER coordinates gene activation are well characterized. However, it remains
      unclear how ER coordinates the immediate repression of genes. We integrated
      genomic transcription, chromosome looping, transcription factor binding, and
      chromatin structure data to analyze the molecular cascade that results from
      estradiol (E2)-induced signaling in human MCF-7 breast cancer cells and addressed
      the context-specific nature of gene regulation. We defined a class of genes that
      are immediately repressed upon estrogen stimulation, and we compared and
      contrasted the molecular characteristics of these repressed genes vs activated
      and unregulated genes. The most striking and unique feature of the repressed gene
      class is transient binding of ER at early time points after estrogen stimulation.
      We also found that p300, a coactivator and acetyltransferase, quantitatively
      redistributes from non-ER enhancers to ER enhancers after E2 treatment. These
      data support an extension of the classic physiological squelching model, whereby
      ER hijacks coactivators from repressed genes and redistributes the coactivators
      to ER enhancers that activate transcription. 

PMID- 25051173
TI  - Effects of pomegranate extract on blood flow and running time to exhaustion.
AB  - Recent research has shown that dietary nitrate has favorable effects on blood
      flow and exercise performance. The purpose of this randomized, double-blind,
      placebo-controlled crossover study was to investigate the acute effects of
      pomegranate extract on blood flow, vessel diameter, and exercise performance in
      active individuals. Nineteen men and women (mean +/- SD: age, 22.2 +/- 2.2 years;
      height, 174.8 +/- 10.7 cm; body mass, 71.9 +/- 13.5 kg) were randomly assigned to
      a placebo (PL) or pomegranate extract (PE) group. Participants performed a
      maximal oxygen consumption treadmill test to determine peak velocity (PV).
      Participants returned after 24-48 h and ingested either PL or PE. Brachial artery
      blood flow was assessed using ultrasound at baseline and 30 min post-ingestion
      (30minPI). Three treadmill runs to exhaustion were performed at 90%, 100%, and
      110% PV. Blood flow was assessed immediately after each exercise bout and 30 min
      postexercise (30minPEx). After a 7-10 day washout, participants repeated the same
      procedures, ingesting the opposite supplement. Separate repeated measures ANOVAs
      were performed for blood flow, vessel diameter, and time to exhaustion (TTE).
      Blood flow was significantly augmented (p = 0.033) 30minPI with PE in comparison
      with PL. Vessel diameter was significantly larger (p = 0.036) 30minPEx with PE.
      Ingestion of PE was found to significantly augment TTE at 90% (p = 0.009) and
      100% PV (p = 0.027). Acute ingestion of PE 30 min before exercise may enhance
      vessel diameter and blood flow and delay fatigue during exercise. Results of the
      current study indicate that PE is ergogenic for intermittent running, eliciting
      beneficial effects on blood flow. 

PMID- 25051174
TI  - Effect of resveratrol on exercise capacity: a randomized placebo-controlled
      crossover pilot study.
AB  - To assess the effect on exercise capacity and tolerability of resveratrol, 13
      healthy, sedentary adult volunteers were enrolled in a randomized crossover study
      comparing resveratrol and placebo over two 4-week periods, with a 2-week time
      between periods when subjects received no treatment. No significant changes in
      exercise duration or aerobic capacity (peak oxygen uptake) were observed.
      Gastrointestinal side effects were more common during resveratrol treatment (77%
      vs. 15%, p = 0.0048). A small reduction in fasting glucose and small but
      statistically significant increases in liver enzymes, total cholesterol, and
      triglycerides were observed, although mean results remained within normal limits.
      There was no change in complete blood count, inflammatory markers, renal
      function, or other measures of liver function. 

PMID- 25051175
TI  - Histone acetyltransferase p300 mediates histone acetylation of PS1 and BACE1 in a
      cellular model of Alzheimer's disease.
AB  - Epigenetic modifications, particularly histone acetylation, have been implicated
      in Alzheimer's disease (AD). While previous studies have suggested that histone
      hypoacetylation may regulate the expression of genes associated with memory and
      learning in AD, little is known about histone regulation of AD-related genes such
      as Presenilin 1(PS1) and beta-site amyloid precursor protein cleaving enzyme
      1(BACE1). By utilizing neuroblastoma N2a cells transfected with Swedish mutated
      human amyloid precursor protein (APP) (N2a/APPswe) and wild-type APP (N2a/APPwt)
      as cellular models of AD, we examined the alterations of histone acetylation at
      the promoter regions of PS1 and BACE1 in these cells. Our results revealed that
      histone H3 acetylation in PS1 and BACE1 promoters is markedly increased in
      N2a/APPswe cells when compared to N2a/APPwt cells and control cells (vector
      transfected), respectively, causing the elevated expression of PS1 and BACE1. In
      addition, expression of histone acetyltransferase (HAT) adenoviral E1A-associated
      300-kDa protein (p300) is dramatically enhanced in N2a/APPswe cells compared to
      N2a/APPwt and control cells. We have further demonstrated the direct binding of
      p300 protein to the PS1 and BACE1 promoters in N2a/APPswe cells. The expression
      levels of H3 acetylation of the PS1 and BACE1 promoters and p300 protein,
      however, were found to be not significantly different in N2a/APPwt cells when
      compared to controls in our studies. Furthermore, curcumin, a natural selective
      inhibitor of p300 in HATs, significantly suppressed the expression of PS1 and
      BACE1 through inhibition of H3 acetylation in their promoter regions in
      N2a/APPswe cells. These findings indicated that histone acetyltransferase p300
      plays a critical role in controlling the expression of AD-related genes through
      regulating the acetylation of their promoter regions, suggesting that p300 may
      represent a novel potential therapeutic target for AD. 

PMID- 25051176
TI  - Multiple EphB receptors mediate dorsal-ventral retinotopic mapping via similar bi
      functional responses to ephrin-B1.
AB  - The projection from the retina to the superior colliculus in mice is organized in
      a retinotopic map that develops through the formation and guidance of
      interstitial branches extended by retinal ganglion cell axons. Bidirectional
      branch guidance along the lateral-medial collicular axis is critical to mapping
      the dorsal-ventral retinal axis. EphB receptor tyrosine kinases expressed in an
      overall low to high dorsal-ventral retinal gradient have been implicated in this
      mapping in response to the graded low to high lateral-medial expression of a
      ligand, ephrin-B1, in the superior colliculus. However, the relative
      contributions of EphBs and ephrin-B1 are not well understood. We examined EphB1,
      EphB2, and EphB3 mutant mice and find that each has ectopic arborizations of
      retinal axon branches lateral to their appropriate termination zone, with no
      qualitative differences in aberrant mapping, suggesting a similar role for each
      EphB. However, the frequency of cases with map defects progressively rises in
      compound EphB mutants coincident with the number of EphB null alleles from one to
      five of the six total alleles indicating that EphB level is critical. We analyzed
      branch extension in vitro and find that dorsal branches, with low EphB levels,
      exhibit a negative response to ephrin-B1, whereas ventral branches, with high
      EphB levels, exhibit a positive response to ephrin-B1. Using EphB mutant retina,
      we show that both of these differential branch extension responses are dependent
      on EphB level. Our findings show a bifunctional action of ephrin-B1 regulated by
      EphB levels that can account for the bidirectional extension of interstitial
      branches required to establish a retinotopic map. 

PMID- 25051177
TI  - Current compound coverage of the kinome.
AB  - Publicly available kinase inhibitors have been analyzed in detail. Nearly 19000
      inhibitors have been identified with activity against 266 different kinases.
      Thus, about half of the human kinome is currently covered with active small
      molecules. The distribution of inhibitors across the kinome is uneven. Most
      available kinase inhibitors are likely to be type I inhibitors. By contrast, type
      II inhibitors are rare but usually have high potency. Kinase inhibitors generally
      display high scaffold diversity. Activity cliffs with an at least 100-fold
      difference in potency are only found for inhibitors of 106 kinases, which is
      partly due to only small numbers of compounds available for many kinases, in
      addition to scaffold diversity. Moreover, kinase inhibitors are less promiscuous
      than often thought. More than 70% of available inhibitors are only annotated with
      a single kinase activity, and only ~1% of the inhibitors are active against five
      or more kinases. 

PMID- 25051178
TI  - Potential use of glucuronylglucosyl-beta-cyclodextrin/dendrimer conjugate (G2) as
      a siRNA carrier for the treatment of familial amyloidotic polyneuropathy.
AB  - We previously reported that 6-O-alpha-(4-O-alpha-D-glucuronyl)-D-glucosyl-beta
      cyclodextrin (GUG-beta-CyD) conjugate with polyamidoamine dendrimer (dendrimer,
      generation 2; G2) (GUG-beta-CDE (G2)) is useful as a gene transfer carrier. In
      the present study, to investigate the potentials of GUG-beta-CDE (G2) as a siRNA
      carrier, we evaluated the RNAi effect of its complex with siRNA against
      transthyretin (TTR) mRNA (siTTR) for the treatment of familial amyloidotic
      polyneuropathy (FAP). Among the various GUG-beta-CDEs (G2) having the different
      degrees of substitution of GUG-beta-CyD (degree of substation (DS) 1.8, 2.5, 3.0
      and 5.0), GUG-beta-CDE (G2, DS 1.8) showed the highest siTTR transfer activity.
      GUG-beta-CDE (G2, DS 1.8)/siTTR complex showed no cytotoxicity in HepG2 cells.
      After intravenous administration of GUG-beta-CDE (G2, DS 1.8)/siTTR complex to
      BALB/c mice, TTR mRNA expression was tended to reduce with negligible change of
      blood chemistry data. Particle size, zeta-potential and cellular association of
      the GUG-beta-CDE (G2, DS 1.8) complex were almost the same as those of the other
      CDEs complexes. Meanwhile, GUG-beta-CDE (G2, DS 1.8)/siTTR complex showed high
      endosomal escaping ability of siTTR in cytoplasm. These findings suggest the
      potential of GUG-beta-CDE (G2, DS 1.8) as a siRNA carrier for the FAP treatment.

PMID- 25051179
TI  - Fabrication of solid strong bases with a molecular-level dispersion of lithium
      sites and high basic catalytic activity.
AB  - New solid strong bases were fabricated at room temperature by grafting lithium
      containing molecular precursors onto beta-cyclodextrin. The solid bases show
      strong basicity with a molecular-level dispersion of lithium sites, which are
      highly active in transesterification reactions and impossible to realize through
      the traditional high-temperature method. 

PMID- 25051181
TI  - Color difference amplification between gold nanoparticles in colorimetric
      analysis with actively controlled multiband illumination.
AB  - Spectral chemical sensing with digital color analysis by using consumer imaging
      devices could potentially revolutionize personalized healthcare. However, samples
      with small spectral variations often cannot be differentiated in color due to the
      nonlinearity of color appearance. In this study, we address this problem by
      exploiting the color image formation mechanism in digital photography. A close
      examination of the color image processing pipeline emphasizes that although the
      color can be represented digitally, it is still a reproducible subjective
      perception rather than a measurable physical property. That makes it possible to
      physically manage the color appearance of a nonradiative specimen through
      engineered illumination. By using scattering light imaging of gold nanoparticles
      (GNPs) as a model system, we demonstrated via simulation that enlarged color
      difference between spectrally close samples could be achieved with actively
      controlled illumination of multiple narrow-band light sources. Experimentally,
      darkfield imaging results indicate that color separation of single GNPs with
      various sizes can be significantly improved and the detection limit of GNP
      aggregation-based colorimetric assays can be much reduced when the conventional
      spectrally continuous white light was replaced with three independently intensity
      controlled laser beams, even though the laser lines were uncorrelated with the
      LSPR maxima of the GNPs. With low-cost narrow-band light sources widely available
      today, this actively controlled illumination strategy could be utilized to
      replace the spectrometer in many spectral sensing applications. 

PMID- 25051180
TI  - Tactile and proprioceptive temporal discrimination are impaired in functional
      tremor.
AB  - BACKGROUND AND METHODS: In order to obtain further information on the
      pathophysiology of functional tremor, we assessed tactile discrimination
      threshold and proprioceptive temporal discrimination motor threshold values in 11
      patients with functional tremor, 11 age- and sex-matched patients with essential
      tremor and 13 healthy controls. RESULTS: Tactile discrimination threshold in both
      the right and left side was significantly higher in patients with functional
      tremor than in the other groups. Proprioceptive temporal discrimination threshold
      for both right and left side was significantly higher in patients with functional
      and essential tremor than in healthy controls. No significant correlation between
      discrimination thresholds and duration or severity of tremor was found.
      CONCLUSIONS: Temporal processing of tactile and proprioceptive stimuli is
      impaired in patients with functional tremor. The mechanisms underlying this
      impaired somatosensory processing and possible ways to apply these findings
      clinically merit further research.

PMID- 25051183
TI  - A novel mechanotactic 3D modeling of cell morphology.
AB  - Cell morphology plays a critical role in many biological processes, such as cell
      migration, tissue development, wound healing and tumor growth. Recent
      investigations demonstrate that, among other stimuli, cells adapt their shapes
      according to their substrate stiffness. Until now, the development of this
      process has not been clear. Therefore, in this work, a new three-dimensional (3D)
      computational model for cell morphology has been developed. This model is based
      on a previous cell migration model presented by the same authors. The new model
      considers that during cell-substrate interaction, cell shape is governed by
      internal cell deformation, which leads to an accurate prediction of the cell
      shape according to the mechanical characteristic of its surrounding micro
      environment. To study this phenomenon, the model has been applied to different
      numerical cases. The obtained results, which are qualitatively consistent with
      well-known related experimental works, indicate that cell morphology not only
      depends on substrate stiffness but also on the substrate boundary conditions. A
      cell located within an unconstrained soft substrate (several kPa) with uniform
      stiffness is unable to adhere to its substrate or to send out pseudopodia. When
      the substrate stiffness increases to tens of kPa (intermediate and rigid
      substrates), the cell can adequately adhere to its substrate. Subsequently, as
      the traction forces exerted by the cell increase, the cell elongates and its
      shape changes. Within very stiff (hard) substrates, the cell cannot penetrate
      into its substrate or send out pseudopodia. On the other hand, a cell is found to
      be more elongated within substrates with a constrained surface. However, this
      elongation decreases when the cell approaches it. It can be concluded that the
      higher the net traction force, the greater the cell elongation, the larger the
      cell membrane area, and the less random the cell alignment. 

PMID- 25051182
TI  - Structure of a membrane-embedded prenyltransferase homologous to UBIAD1.
AB  - Membrane-embedded prenyltransferases from the UbiA family catalyze the Mg2+
      dependent transfer of a hydrophobic polyprenyl chain onto a variety of acceptor
      molecules and are involved in the synthesis of molecules that mediate electron
      transport, including Vitamin K and Coenzyme Q. In humans, missense mutations to
      the protein UbiA prenyltransferase domain-containing 1 (UBIAD1) are responsible
      for Schnyder crystalline corneal dystrophy, which is a genetic disease that
      causes blindness. Mechanistic understanding of this family of enzymes has been
      hampered by a lack of three-dimensional structures. We have solved structures of
      a UBIAD1 homolog from Archaeoglobus fulgidus, AfUbiA, in an unliganded form and
      bound to Mg2+ and two different isoprenyl diphosphates. Functional assays on
      MenA, a UbiA family member from E. coli, verified the importance of residues
      involved in Mg2+ and substrate binding. The structural and functional studies led
      us to propose a mechanism for the prenyl transfer reaction. Disease-causing
      mutations in UBIAD1 are clustered around the active site in AfUbiA, suggesting
      the mechanism of catalysis is conserved between the two homologs. 

PMID- 25051184
TI  - Tonsillitis.
AB  - INTRODUCTION: The definition of severe recurrent throat infections is arbitrary,
      but recent criteria have defined severe tonsillitis as: five or more episodes of
      true tonsillitis a year; symptoms for at least 1 year; and episodes that are
      disabling and prevent normal functioning. Diagnosis of acute tonsillitis is
      clinical, and it can be difficult to distinguish viral from bacterial infections.
      Rapid antigen testing has a very low sensitivity in the diagnosis of bacterial
      tonsillitis, but more accurate tests take longer to deliver results. Bacteria are
      cultured from few people with tonsillitis. Other causes include infectious
      mononucleosis from Epstein-Barr virus infection, cytomegalovirus, toxoplasmosis,
      HIV, hepatitis A, and rubella. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical question: What are the effects
      of tonsillectomy in children and adults with acute recurrent or chronic throat
      infections? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to April 2014 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 15 studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions: cold
      steel tonsillectomy and diathermy tonsillectomy.

PMID- 25051186
TI  - Reactivity of kiteplatin with S-donor biomolecules and nucleotides.
AB  - Kiteplatin, (cis-1,4-DACH)dichloridoplatinum(ii), contains an isomeric form of
      the carrier ligand present in the successful antitumor drug oxaliplatin and has
      been recently found to be very active against oxaliplatin-resistant colon
      cancers, confirming that, by changing the nature of the amine ligand, it is
      possible to obtain platinum drugs that are not cross-resistant to those already
      in clinical use. Apart from interaction with DNA, another factor that can affect
      the activity of platinum drugs is their metabolic fate in the cellular
      environment. Therefore, kiteplatin has been reacted with S-donor biomolecules,
      such as glutathione, cysteine, and methionine. The investigation has further
      confirmed the different reactivity of methionine as compared to cysteine
      containing peptides and has unraveled the possibility of cis-1,4-DACH to become
      mono-coordinated with one free end (a situation never seen for isomeric 1,2-DACH
      ligands) and to labilize cis ligands as a consequence of its large steric
      hindrance. The reaction of kiteplatin-GSH adducts with 5'-GMP has also shown how
      the reaction products can be different depending upon the aerobic or anaerobic
      reaction conditions used. 

PMID- 25051185
TI  - Allyl isothiocyanate ameliorates angiogenesis and inflammation in dextran sulfate
      sodium-induced acute colitis.
AB  - Allyl isothiocyanate (AITC) is a phytochemical found in cruciferous vegetables
      that has known chemopreventive and chemotherapeutic activities. Thus far, the
      antiangiogenic activity of AITC has not been reported in in vivo studies. Herein,
      we investigated the effect of AITC on angiogenesis and inflammation in a mouse
      model of colitis. Experimental colitis was induced in mice by administering 3%
      dextran sulfate sodium via drinking water. To monitor the activity of AITC in
      this model, we measured body weight, disease activity indices, histopathological
      scores, microvascular density, myeloperoxidase activity, F4/80 staining,
      inducible nitric oxide synthase (iNOS) expression, cyclooxygenase-2 (COX-2)
      expression, and vascular endothelial growth factor (VEGF)-A/VEGF receptor 2
      (VEGFR2) expression in the mice. We found that AITC-treated mice showed less
      weight loss, fewer clinical signs of colitis, and longer colons than vehicle
      treated mice. AITC treatment also significantly lessened the disruption of
      colonic architecture that is normally associated with colitis and repressed the
      microvascularization response. Further, AITC treatment reduced both leukocyte
      recruitment and macrophage infiltration into the inflamed colon, and the
      mechanism these activities involved repressing iNOS and COX-2 expression.
      Finally, AITC attenuated the expression of VEGF-A and VEGFR2. Thus, AITC may have
      potential application in treating conditions marked by inflammatory-driven
      angiogenesis and mucosal inflammation. 

PMID- 25051187
TI  - Legal aspects of public health: difficulties in controlling vector-borne and
      zoonotic diseases in Brazil.
AB  - In recent years, vector-borne and zoonotic diseases have become a major challenge
      for public health. Dengue fever and leptospirosis are the most important
      communicable diseases in Brazil based on their prevalence and the healthy life
      years lost from disability. The primary strategy for preventing human exposure to
      these diseases is effective insect and rodent control in and around the home.
      However, health authorities have difficulties in controlling vector-borne and
      zoonotic diseases because residents often refuse access to their homes. This
      study discusses aspects related to the activities performed by Brazilian health
      authorities to combat vector-borne and zoonotic diseases, particularly
      difficulties in relation to the legal aspect, which often impede the quick and
      effective actions of these professionals. How might it be possible to reconcile
      the need to preserve public health and the rule on the inviolability of the home,
      especially in the case of abandoned properties or illegal residents and the
      refusal of residents to allow the health authority access? Do residents have the
      right to hinder the performance of health workers even in the face of a
      significant and visible focus of disease transmission? This paper argues that a
      comprehensive legal plan aimed at the control of invasive vector-borne and
      zoonotic diseases including synanthropic animals of public health importance
      should be considered. In addition, this paper aims to bridge the gap between
      lawyers and public health professionals and to facilitate communication between
      them. 

PMID- 25051189
TI  - Gold nanoparticles as electron reservoir redox catalysts for 4-nitrophenol
      reduction: a strong stereoelectronic ligand influence.
AB  - The stereoelectronic properties of the stabilizing ligands of gold nanoparticles
      (AuNPs) are shown to play a considerable role in their catalytic efficiency for 4
      nitrophenol reduction by NaBH4, consistent with a mechanism involving
      restructuration of the AuNP surface that behaves as an "electron reservoir". 

PMID- 25051188
TI  - Use of dried blood spots to define antibody response to the Strongyloides
      stercoralis recombinant antigen NIE.
AB  - An approach to improve the diagnosis of Strongyloides stercoralis infection is
      the use of serologic assays utilising the NIE antigen from S. stercoralis, with
      good diagnostic sensitivity and excellent specificity reported. Detection of
      antibody eluted from dried blood spots (DBS) has shown utility in large-scale
      seroepidemiological studies for a range of conditions and is appealing for use
      with children where sample collection is difficult. We adapted an existing NIE
      enzyme linked immunosorbent assay (ELISA) for the testing of strongyloides
      antibody response on DBS, and evaluated it in a population screening and mass
      drug administration programme (MDA) for strongyloidiasis conducted in an
      Australian indigenous community. Study participants were treated with 200 MUg/kg
      ivermectin (>15 kg) or 3* 400 mg albendazole (<15kg). The sensitivity of the NIE
      DBS-ELISA was determined by receiver operator characteristic (ROC) analysis to be
      85.7%. A total of 214 DBS were collected from 184 participants across two
      screening and MDA encounters. A total of 27 of 164 participants (16.5%) tested
      positive for S. stercoralis NIE-DBS prior to MDA treatment, and 6 of 50
      participants (12.0%) tested positive after treatment. These prevalence values are
      similar to those documented by standard serology in the same community. For 30
      participants where a DBS was collected at both MDA 1 and 2, a significant decline
      in ELISA values was evident post treatment (0.12-0.02, p=0.0012). These results
      are in agreement with previous studies documenting the high seroprevalence of S.
      stercoralis in remote Australian Indigenous communities, and suggest that
      collection of dried blood spots may be a useful approach for field diagnosis of
      S. stercoralis seroprevalence.

PMID- 25051190
TI  - Protective effects of the p38 MAPK inhibitor SB203580 on NMDA-induced injury in
      primary cerebral cortical neurons.
AB  - The p38 pathway, which is important in mitogen-activated protein kinase (MAPK)
      family protein signaling, leads to mitochondrial dysfunction and activation of
      caspase-3. B-cell lymphoma 2 (Bcl-2) family members are involved in the
      regulation of activities associated with the survival and death of neurons
      through apoptosis and have important functions in most types of apoptosis. In the
      present study, the effects of the p38 MAPK inhibitor SB203580 on N-methyl-d
      aspartate (NMDA)-induced cerebral cortical neuron apoptosis were observed to
      further analyze the possible mechanisms of NMDA-induced neuronal death. Cultured
      primary cortical neurons were randomly divided into five groups: A control group,
      NMDA group and three SB203580 interventional groups. The lactate dehydrogenase
      (LDH) and MTT assays were employed to investigate the effects of the drugs on
      apoptosis. The morphology of apoptotic cells was observed using acridine
      orange/ethidium bromide (AO/EB) fluorescence staining. The expression levels of
      phospho-(p)-p38MAPK, Bcl-2 and Bcl-2-associated X (Bax) were assessed by
      immunohistochemical methods and western blot analysis to investigate the possible
      underlying protective mechanisms. The cell viability markedly decreased following
      incubation with NMDA. The protein levels of cell death repressor Bcl-2 and the
      levels of Bcl-2/Bax were downregulated. The protein levels of p-p38MAPK and cell
      death promoter Bax increased significantly in cells with NMDA treatment. However,
      these changes were inhibited by SB203580 treatment, particularly in the high-dose
      group. Neuronal death induced by NMDA in primary cortical neurons was caused in
      part by apoptosis, which was mediated through the activation of the p38 signaling
      pathway by NMDA. SB203580 has neuroprotective effects against NMDA-induced
      apoptosis.

PMID- 25051191
TI  - Chemo- and bioinformatics resources for in silico drug discovery from medicinal
      plants beyond their traditional use: a critical review.
AB  - In silico approaches have been widely recognised to be useful for drug discovery.
      Here, we consider the significance of available databases of medicinal plants and
      chemo- and bioinformatics tools for in silico drug discovery beyond the
      traditional use of folk medicines. This review contains a practical example of
      the application of combined chemo- and bioinformatics methods to study
      pleiotropic therapeutic effects (known and novel) of 50 medicinal plants from
      Traditional Indian Medicine.

PMID- 25051192
TI  - Medical-attention injuries in community Australian football: a review of 30 years
      of surveillance data from treatment sources.
AB  - OBJECTIVE: In recent reports, Australian football has outranked other team sports
      in the frequency of hospitalizations and emergency department (ED) presentations.
      Understanding the profile of these and other "medical-attention" injuries is
      vital for developing preventive strategies that can reduce health costs. The
      objective of this review was to describe the frequency and profile of Australian
      football injuries presenting for medical attention. DATA SOURCES: A systematic
      search was carried out to identify peer-reviewed articles and reports presenting
      original data about Australian football injuries from treatment sources
      (hospitals, EDs, and health-care clinics). Data extracted included injury
      frequency and rate, body region, and nature and mechanism of injury. MAIN
      RESULTS: Following literature search and review, 12 publications were included.
      In most studies, Australian football contributed the greatest number of injuries
      out of any sport or recreation activity. Hospitals and EDs reported a higher
      proportion of upper limb than lower limb injuries, whereas the opposite was true
      for sports medicine clinics. In hospitals, fractures and dislocations were most
      prevalent out of all injuries. In EDs and clinics, sprains/strains were most
      common in adults and superficial injuries were predominant in children. Most
      injuries resulted from contact with other players or falling. CONCLUSIONS: The
      upper limb was the most commonly injured body region for Australian football
      presentations to hospitals and EDs. Strategies to prevent upper limb injuries
      could reduce associated public health costs. However, to understand the full
      extent of the injury problem in football, treatment source surveillance systems
      should be supplemented with other datasets, including community club-based
      collections.

PMID- 25051193
TI  - Concussion reporting intention: a valuable metric for predicting reporting
      behavior and evaluating concussion education.
AB  - OBJECTIVE: This study aimed to evaluate whether preseason concussion knowledge
      and reporting intention predicted in-season concussion reporting behavior.
      DESIGN: Prospective cohort study. SETTING: Collegiate athletic facility of each
      participating team. PARTICIPANTS: National Collegiate Athletic Association
      Division I men's ice hockey players in 1 conference of competition (n = 116).
      INDEPENDENT VARIABLES: Intention to report symptoms of a "minor" concussion and
      concussion knowledge were assessed at preseason. MAIN OUTCOME MEASURES:
      Postseason recall of non-report of postimpact symptoms. RESULTS: Preseason
      concussion knowledge was not significantly associated with in-season reporting
      behavior. Intention to report concussion symptoms was significantly related to in
      season reporting behavior. There was a significant interaction between the number
      of different symptoms experienced and both preseason reporting intention and in
      season reporting behavior. CONCLUSIONS: Evaluations of concussion education
      programs tend to measure concussion knowledge. The present findings suggest that
      reporting intention may be more strongly predictive of reporting behavior than
      concussion knowledge and should be included in evaluations of concussion
      effectiveness. New concussion education initiatives should consider targeting
      psychosocial constructs that increase reporting intention. CLINICAL RELEVANCE:
      Sports medicine clinicians who are involved in evaluating concussion education
      programs should measure constructs other than just concussion knowledge.
      Intention, to report symptoms or to continue play while experiencing symptoms of
      a concussion, seems to be an important and feasible construct to include as part
      of proximal evaluations of education effectiveness.

PMID- 25051194
TI  - Brain or strain? Symptoms alone do not distinguish physiologic concussion from
      cervical/vestibular injury.
AB  - OBJECTIVE: To compare symptoms in patients with physiologic postconcussion
      disorder (PCD) versus cervicogenic/vestibular PCD. We hypothesized that most
      symptoms would not be equivalent. In particular, we hypothesized that cognitive
      symptoms would be more often associated with physiologic PCD. DESIGN:
      Retrospective review of symptom reports from patients who completed a 22-item
      symptom questionnaire. SETTING: University-based concussion clinic. PATIENTS:
      Convenience sample of 128 patients who had symptoms after head injury for more
      than 3 weeks and who had provocative treadmill exercise testing. INDEPENDENT
      VARIABLES: Subjects were classified as either physiologic PCD (abnormal treadmill
      performance and a normal cervical/vestibular physical examination) or
      cervicogenic/vestibular PCD (CGV, normal treadmill performance, and an abnormal
      cervical/vestibular physical examination). MAIN OUTCOME MEASURES: Self-reported
      symptoms. Univariate and multivariate methods, including t tests, tests of
      equivalence, a logistic regression model, k-nearest neighbor analysis,
      multidimensional scaling, and principle components analysis were used to see
      whether symptoms could distinguish PCD from CGV. RESULTS: None of the statistical
      methods used to analyze self-reported symptoms was able to adequately distinguish
      patients with PCD from patients with CGV. CONCLUSIONS: Symptoms after head
      injury, including cognitive symptoms, have traditionally been ascribed to brain
      injury, but they do not reliably discriminate between physiologic PCD and
      cervicogenic/vestibular PCD. Clinicians should consider specific testing of
      exercise tolerance and perform a physical examination of the cervical spine and
      the vestibular/ocular systems to determine the etiology of postconcussion
      symptoms. CLINICAL RELEVANCE: Symptoms after head injury, including cognitive
      symptoms, do not discriminate between concussion and cervical/vestibular injury.

PMID- 25051195
TI  - An unusual case of unintentional firearm death of a 3-year-old child.
AB  - The authors report the case of an accidental death of a 3-year-old child who
      unintentionally shot himself while he was handling his father's handgun.The
      peculiarity of the observed injury makes the case particularly interesting, along
      with the fact that, in Italy, unintentional firearm-related deaths are rather
      uncommon among children and adolescents.Because of the presence of only 1 bullet
      hole on the parietal-occipital region, radiological cranial examinations were
      performed before proceeding with the autopsy.Computed tomographic scans were
      useful to confirm the entrance site of the bullet and, especially, to establish
      the trajectory with the whole spectrum of fractures.The case shows that the
      unusual entrance site of the bullet through the nose led to a fatal cranial
      injury, as a result of curiosity of a 3-year-old child in the presence of an
      unsupervised handgun. 

PMID- 25051196
TI  - Diphenhydramine's role in death investigations: an examination of diphenhydramine
      prevalence in 2 US geographical areas.
AB  - PURPOSE: Diphenhydramine (DPH), an over-the-counter first-generation H1 receptor
      antagonist, is not a common drug of abuse; however, it is encountered in cases of
      overdose both in the clinical setting and in death investigations. The toxicology
      laboratories in the Tarrant County Medical Examiner's Office and the District of
      Columbia Office of The Chief Medical Examiner analyze antemortem and postmortem
      specimens. Presented are the findings of this evaluation and detailed histories
      of cases involving DPH. METHODS: Toxicology reports, autopsy reports, and death
      investigator narratives were obtained in cases involving DPH at toxic and lethal
      levels in which this compound was the primary cause or a contributing factor in
      the death. RESULTS: Blood concentrations were quantified at a range of 2870 to
      21,263 ng/mL. A rare occurrence of DPH abuse via documented intravenous
      administration leading to death is presented. The cases presented here generally
      involved much higher concentrations of DPH and an older population than those in
      previous published data regarding DPH's role in death investigation and abuse.
      CONCLUSIONS: As people seek legal alternative drugs to abuse and with the ease of
      obtaining information via online forums, there is a potential to see an increase
      in the number of cases involving excessive use of DPH.

PMID- 25051197
TI  - The acoustical cues to sound location in the guinea pig (Cavia porcellus).
AB  - There are three main acoustical cues to sound location, each attributable to
      space- and frequency-dependent filtering of the propagating sound waves by the
      outer ears, head, and torso: Interaural differences in time (ITD) and level (ILD)
      as well as monaural spectral shape cues. While the guinea pig has been a common
      model for studying the anatomy, physiology, and behavior of binaural and spatial
      hearing, extensive measurements of their available acoustical cues are lacking.
      Here, these cues were determined from directional transfer functions (DTFs), the
      directional components of the head-related transfer functions, for 11 adult
      guinea pigs. In the frontal hemisphere, monaural spectral notches were present
      for frequencies from ~10 to 20 kHz; in general, the notch frequency increased
      with increasing sound source elevation and in azimuth toward the contralateral
      ear. The maximum ITDs calculated from low-pass filtered (2 kHz cutoff frequency)
      DTFs were ~250 MUs, whereas the maximum ITD measured with low-frequency tone pips
      was over 320 MUs. A spherical head model underestimates ITD magnitude under
      normal conditions, but closely approximates values when the pinnae were removed.
      Interaural level differences (ILDs) strongly depended on location and frequency;
      maximum ILDs were <10 dB for frequencies <4 kHz and were as large as 40 dB for
      frequencies >10 kHz. Removal of the pinna reduced the depth and sharpness of
      spectral notches, altered the acoustical axis, and reduced the acoustical gain,
      ITDs, and ILDs; however, spectral shape features and acoustical gain were not
      completely eliminated, suggesting a substantial contribution of the head and
      torso in altering the sounds present at the tympanic membrane.

PMID- 25051198
TI  - Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by
      inhibiting WWP1, Smurf1 and Smurf2.
AB  - Prostate cancer is the most common malignancy diagnosed in males, and bone
      metastases remain a significant source of morbidity and mortality in this
      population. Ubiquitin ligase E3s and proteasomes were thought to play essential
      roles in the development of cancers, therefore, they were proposed as therapy
      targets for the treatment of solid and hematological malignancies. Bortezomib,
      well-known as a proteasome inhibitor, has been observed with exact anticancer
      effect both in cell and animal models for several solid tumor types, including
      prostate cancer. To explore activities of the ubiquitin ligase E3s WWP1, Smurf1
      and Smurf2 in oncogenesis and bone metastasis of prostate cancer, as well as in
      the functional mechanism of bortezomib in preventing prostate cancer,
      transcription and expression levels of WWP1, Smurf1 and Smurf2 genes in cell
      lines or tissues of benign prostate hyperplasia and human prostate cancer with
      and without bone metastasis were tested. Moreover, human prostate cancer PC3 cell
      lines were treated with bortezomib at different concentration gradients and then
      their proliferation at different time points, mRNA and protein levels were
      investigated. The results indicated that transcription and expression levels of
      WWP1, Smurf1 and Smurf2 genes in prostate cancer without bone metastasis were
      significantly higher compared to those in benign prostate hyperplasia (P<0.05),
      whereas significantly lower than prostate cancer metastatic to bone (P<0.05).
      Furthermore, bortezomib reduced the transcription and expression levels of WWP1,
      Smurf1 and Smurf2 genes in prostate cancer cell lines in a dose-dependent manner,
      thus, inhibiting the proliferation of prostate cancer cells. Elevated
      transcription and expression levels of ubiquitin ligase E3s WWP1, Smurf1 and
      Smurf2 genes may be the mechanisms of occurrence, development and metastasis of
      prostate cancer. In addition, bortezomib can prevent prostate cancer and its bone
      metastasis by downregulating WWP1, Smurf1 and Smurf2. 

PMID- 25051200
TI  - The kinds of information that support novel associative object priming and how
      these differ from those that support item priming.
AB  - We investigated how the information that supports novel associative and item
      object priming differs under identical study/test conditions. In Experiments 1
      and 2, participants rated the meaningfulness of sentences linking two object
      pictures at study. At test, they performed either a size judgement or an
      associative recognition memory task on intact, recombined and novel picture
      (Experiment 1) or word (Experiment 2) associations. Associative priming was
      modulated by subjective meaningfulness of the encoded links, and depended on
      study/test perceptual overlap. In contrast, item priming was neither affected by
      the meaningfulness of the sentences nor by study/test changes in the stimulus
      presentation format. Associative priming and recognition were behaviourally
      dissociated, and associative recognition was probably too slow to have seriously
      contaminated associative priming. In Experiment 3, participants performed a
      perceptually oriented task during both experimental phases, and both associative
      and item priming were observed. These results suggest that associative priming
      depends on stored associative semantic and perceptual information when the test
      task requires flexible retrieval of associative information. Under the same
      conditions, item priming may only require activation of items' semantic
      properties. When both study and test tasks stress perceptual processing,
      retrieval of perceptual information is sufficient to support both kinds of
      priming. 

PMID- 25051199
TI  - Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2
      production in keratinocyte is related to reactive oxygen species, CYP1A1, Src,
      EGFR and Ras signaling.
AB  - AIMS: Chewing of betel quid (BQ) increases the risk of oral cancer and oral
      submucous fibrosis (OSF), possibly by BQ-induced toxicity and induction of
      inflammatory response in oral mucosa. METHODS: Primary gingival keratinocytes (GK
      cells) were exposed to areca nut (AN) components with/without inhibitors.
      Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol- 2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay. mRNA and protein expression was evaluated by
      reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting.
      PGE2/PGF2alpha production was measured by enzyme-linked immunosorbent assays.
      RESULTS: Areca nut extract (ANE) stimulated PGE2/PGF2alpha production, and
      upregulated the expression of cyclooxygenase-2 (COX-2), cytochrome P450 1A1
      (CYP1A1) and hemeoxygenase-1 (HO-1), but inhibited expression of keratin 5/14,
      cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor
      receptor (EGFR), Src and Ras signaling pathways. ANE-induced COX-2, keratin 5,
      keratin 14 and cdc25C expression as well as PGE2 production were differentially
      regulated by alpha-naphthoflavone (a CYP 1A1/1A2 inhibitor), PD153035 (EGFR
      inhibitor), pp2 (Src inhibitor), and manumycin A (a Ras inhibitor). ANE-induced
      PGE2 production was suppressed by piper betle leaf (PBL) extract and
      hydroxychavicol (two major BQ components), dicoumarol (a NAD(P)H: Quinone
      Oxidoreductase--NQO1 inhibitor) and curcumin. ANE-induced cytotoxicity was
      inhibited by catalase and enhanced by dicoumarol, suggesting that AN components
      may contribute to the pathogenesis of OSF and oral cancer via induction of
      aberrant differentiation, cytotoxicity, COX-2 expression, and PGE2/PGF2alpha
      production. CONCLUSIONS: CYP4501A1, reactive oxygen species (ROS), EGFR, Src and
      Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral
      cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE
      induced inflammatory response.

PMID- 25051201
TI  - A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy
      driven by the hTERT promoter in a murine colorectal cancer model.
AB  - A therapeutic vaccine against minimal residual cancer cells is needed for the
      treatment of patients with colorectal cancer. Several gene therapy studies have
      revealed that the combination of a suicide gene and cytokine gene might induce
      effective antitumor immunity. In this study, we constructed an interleukin (IL)
      18 and herpes simplex virus-thymidine kinase (HSV-TK) expression vector driven by
      the human telomerase reverse transcriptase (hTERT) promoter to study the efficacy
      of combination gene therapy with IL-18 and the HSV-TK suicide gene. Low
      immunogenic colon 26 cells were used for transfection and inoculation into
      syngeneic BALB/c mice. Large established tumors of colon 26 transfectants
      expressing IL-18 and HSV-TK driven by the hTERT promoter were completely
      eradicated after GCV administration in syngeneic BALB/c mice. Immunohistochemical
      analysis at the tumor rejection sites revealed enormous infiltrations of CD8+ T
      lymphocytes as well as CD4+ T lymphocytes and CD11b+ monocytes. Moreover,
      established distant tumors were completely eradicated by vaccination with the IL
      18 and HSV-TK transfectants in combination with GCV. These data suggest that the
      IL-18 and suicide gene therapy can elicit antitumor specific immunity. In
      conclusion, gene therapy with IL-18 and HSV-TK plasmid vector driven by the hTERT
      promoter may be useful for cancer vaccination. 

PMID- 25051202
TI  - BRAF V600 mutations and pathological features in Japanese melanoma patients.
AB  - Ultraviolet radiation is a risk factor for BRAF V600 mutations frequently found
      in melanomas that cause constitutive BRAF activation. Primary sites of melanoma
      and the frequency of BRAF mutations might differ between races. Melanoma is rare
      in Japan (1500-2000 cases/year compared with 132 000/year worldwide) and the
      frequency and distribution of BRAF V600 mutations are unknown. We aimed to
      investigate the frequency of BRAF V600 mutations in a cohort of Japanese patients
      with melanoma and determine the relationship between mutations and
      clinical/pathologic features. DNA was extracted from 80 formalin-fixed, paraffin
      embedded tumours from individuals diagnosed with melanoma. BRAF V600 mutations
      were detected using the Cobas 4800 System with z480 Analyzer and Cobas 4800 BRAF
      V600 Mutation Test reagents. BRAF V600 mutations were detected in 41.8% of tested
      tumours, with an invalid rate of 1.3%. The mutation rate was more than 60% in
      patients aged less than 60 years and more than 36% in patients with stage III/IV
      disease. No sex difference in the mutation rate was observed. BRAF V600 mutations
      were detected in 18.8% of acral lentiginous melanomas (ALMs), 64.7% of
      superficial spreading melanomas, 50.0% of lentigo maligna melanomas and 20.0% of
      nodular melanomas. Although the mutation rate was low in ALMs, 36.4% were
      mutation positive at stage III/IV compared with 9.5% at stage I/II. This study
      confirmed associations among BRAF V600 mutations, pathological features and
      subtypes of melanoma. BRAF V600 mutations were more frequent in late-stage ALMs
      than in early-stage ALMs. Superficial spreading melanomas had similar mutation
      rates at all stages. These insights suggest improved treatment predictions for
      stage III/IV melanoma patients. 

PMID- 25051203
TI  - Sunlight-promoted photocatalytic hydrogen gas evolution from water-suspended
      cellulose: a systematic study.
AB  - This work presents a systematic study of cellulose (CLS) as a sacrificial biomass
      for photocatalytic H2 evolution from water. The idea is indeed to couple a
      largely available and not expensive biomass, and water, with a renewable energy
      like solar radiation. An aqueous CLS suspension irradiated either at 366 nm (UV
      A) or under sunlight in the presence of Pt/TiO2 behaves as a H2 evolving system.
      The effects of irradiation time, catalyst and CLS concentrations, pH and water
      salinity are studied. Addition of CLS to the sample significantly improved H2
      evolution from water splitting, with yields up to ten fold higher than those
      observed in neat water. The mechanism of the photocatalytic process relies on the
      TiO2-mediated CLS hydrolysis, under irradiation. The polysaccharide
      depolymerisation generates water-soluble species and intermediates, among them 5
      hydroxymethylfurfural (HMF) was identified. These intermediates are readily
      oxidized following the glucose photoreforming, thus enhancing water hydrogen ion
      reduction to give gas-phase H2. The formation of "colored" by-products from HMF
      self-polymerization involves a sort of "in situ dye sensitization" that allows an
      effective photoreaction even under solar light. The procedure is evaluated and
      successfully extended on cellulosic biomasses, i.e. rice husk and alfalfa
      (Medicago sativa) stems, not previously investigated for this application. 

PMID- 25051204
TI  - Stimuli-responsive polypropylene for the sustained delivery of TPGS and
      interaction with erythrocytes.
AB  - Hemocompatibility and oxidative stress are significant for blood-contacting
      devices. In this study, N-isopropylacrylamide (NIPAAm) and N-(3
      aminopropyl)methacrylamide hydrochloride (APMA) were cografted on polypropylene
      (PP) membrane using ultraviolet grafting to load antioxidative d-alpha-tocopheryl
      polyethylene glycol 1000 succinate (TPGS) and control the release of TPGS. The
      immobilization of NIPAAm and APMA onto PP membrane was confirmed by attenuated
      total reflectance Fourier-transform infrared spectroscopy and X-ray photoelectron
      spectroscopy. Combined with data from platelet adhesion, red blood cell (RBC)
      attachment, and hemolysis rate, the hemocompatibility of PP was significantly
      improved. An in-depth characterization using hemolysis rate test, scanning
      electron microscopy, atomic force microscopy, and confocal laser scanning
      microscopy was conducted to confirm that the mechanism of the release of TPGS
      interacted with RBCs was different at different stages. The release of TPGS from
      the loading PP membranes affected hemolysis at different stages. At the early
      stage of release, TPGS maintained the tiny (nanometer-sized) tubers on the
      membrane surface and enhanced the membrane permeabilization by generating
      nanosized pores on the cell membranes. Afterward, the incorporated TPGS slowed
      the lipid peroxidation of erythrocytes and filled in the lipid bilayer of
      erythrocyte to prevent hemolysis. Thus, the approach implemented to graft NIPAAm
      and APMA and load TPGS was suitable to develop medical device with excellent
      hemocompatibility and antioxidative property. 

PMID- 25051205
TI  - Physical-capacity-related genetic polymorphisms in children with cystic fibrosis.
AB  - In patients with cystic fibrosis (CF), physical capacity (PC) has been correlated
      with mortality risk. In turn, PC is dependent on genetic factors. This study
      examines several polymorphisms associated with PC and health-related phenotype
      traits (VO2peak, FEV1, FVC, PImax and muscular strength) in a group of children
      with CF (n = 66, primary purpose). The same analyses were also performed in a
      control group of healthy children (n = 113, secondary purpose). The polymorphisms
      determined were classified as muscle function polymorphisms (ACE rs1799752; AGT
      rs699; ACTN3 rs1815739; PTK2 rs7843014 and rs7460; MSTN rs1805086; TRHR
      rs7832552; NOS3 rs2070744) or energy metabolism polymorphisms (PPARGC1A
      rs8192678; NRF1 rs6949152; NRF2 rs12594956; TFAM rs1937; PPARD rs2267668; ACSL1
      rs6552828). No significant polymorphism/phenotype correlations were detected in
      children with CF, with marginal associations being observed between NOS3
      rs2070744 and VO2peak and FEV1, as well as between PPARGC1A rs8192678 and FEV1.
      Overall, similar findings were observed in the control group, i.e., no major
      associations. The PC-related polymorphisms examined seem to have no effects on
      the PC or health of children with CF. 

PMID- 25051208
TI  - UEMS--Position Paper. New technologies designed to improve functioning: the role
      of the physical and rehabilitation medicine physician.

PMID- 25051207
TI  - Heart Rate Variability (HRV) modifications in adult hemiplegic patients after
      botulinum toxin type A (nt-201) injection.
AB  - BACKGROUND: The most important adverse effect of BoNT-A is the systemic diffusion
      of the toxin. There is some evidence that the administration of high doses can
      increase the risk of systemic diffusion and the development of clinically evident
      adverse effects, however an international consensus does not exist about its
      maximum dose. AIM: The aim of this study was to evaluate changes in autonomic
      heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA
      injection in spastic stroke patients. Moreover, the treatment safety by
      monitoring adverse events occurrence was assessed. DESIGN: Case control study.
      POPULATION: Eleven stroke survivors with spastic hemiplegia. METHODS: Patients
      were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201;
      Xeomin(r), Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12
      units/Kg. Each patient underwent an ECG recording before injection and 10 days
      after treatment. Linear and non-linear Heart Rate variability (HRV) measures were
      derived from ECGs with a dedicated software. RESULTS: None of the variable
      considered showed statistically significant changes after BoNT-A injection.
      CONCLUSION: The use of incobotulinumtoxinA in adult patients at doses up to 12
      units/kg seems to be safe regarding autonomic heart drive. CLINICAL
      REHABILITATION IMPACT: The use of IncobotulinumtoxinA up to 600 units could be a
      safe therapeutic option in spastic hemiplegic stroke survivors.

PMID- 25051209
TI  - Functional performance of female patients more than 6 months after total hip
      arthroplasty shows greater improvement with weight-bearing exercise than with non
      weight-bearing exercise. Randomized controlled trial.
AB  - BACKGROUND: Impaired functional performance and decreased muscle strength and
      muscle atrophy generally persist for a long period after total hip arthroplasty
      (THA). AIM: To investigate the effects of weight-bearing (WB) and non-weight
      bearing (NWB) exercises on functional performance, Harris hip score (HHS), muscle
      strength and muscle thickness in women after THA. DESIGN: A randomised,
      controlled trial. SETTING: Community. POPULATION: Sixty-five women who had
      undergone unilateral or bilateral THA at least 6 months before enrolment in the
      study. METHODS: Participants were randomly allocated to the following groups: WB
      (n = 22), NWB (n = 21) and control (n = 22) groups. Participants in the WB and
      NWB groups performed daily home exercise programs for 8 weeks. Functional
      performance (timed up and go, sit-to-stand, stair climbing, walking speed and 3
      min walk test), HHS, isometric muscle strength of the hip and knee muscle and
      gluteus and quadriceps muscle thickness were measured at baseline and after 8
      weeks. RESULTS: An intention-to-treat analysis revealed that both the
      intervention groups exhibited significant improvements in almost all functional
      performance measures compared with the control group. Furthermore, the WB group
      showed significantly greater pre-post changes in the sit-to-stand and 3-min walk
      test compared with the NWB group. In terms of HHS, only the WB group showed
      significantly greater improvement compared with the control group. Relative to
      the control group, improvements in all isometric strength measures were observed
      in both the intervention groups. Significant improvement in quadriceps muscle
      thickness was observed in the WB group compared with the control group. However,
      no significant difference was observed among the three groups in pre-post changes
      in gluteus muscle thickness. CONCLUSION: WB and NWB home exercise programs were
      both effective for improving functional performance and muscle strength in women
      after THA. However, the WB exercise was more effective than the NWB exercise for
      improving sit-to-stand ability and walking endurance. CLINICAL REHABILITATION
      IMPACT: In this study, we demonstrated that the WB exercise was more effective
      than the NWB exercise for improving functional performance in patients after THA.

PMID- 25051210
TI  - Exoskeletal cuticle differentiation during intramarsupial development of
      Porcellio scaber (Crustacea: Isopoda).
AB  - Exoskeletal crustacean cuticle is a calcified apical extracellular matrix of
      epidermal cells, illustrating the chitin-based organic scaffold for
      biomineralization. Studies of cuticle formation during molting reveal significant
      dynamics and complexity of the assembly processes, while cuticle formation during
      embryogenesis is poorly investigated. This study reveals in the terrestrial
      isopod Porcellio scaber, the ultrastructural organization of the differentiating
      precuticular matrices and exoskeletal cuticles during embryonic and larval
      intramarsupial development. The composition of the epidermal matrices was
      obtained by WGA lectin labelling and EDXS analysis. At least two precuticular
      matrices, consisting of loosely arranged material with overlying electron dense
      lamina, are secreted by the epidermis in the mid-stage embryo. The prehatching
      embryo is the earliest developmental stage with a cuticular matrix consisting of
      an epicuticle and a procuticle, displaying WGA binding and forming cuticular
      scales. In newly hatched marsupial larva manca, a new cuticle is formed and
      calcium sequestration in the cuticle is evident. Progression of larval
      development leads to the cuticle thickening, structural differentiation of
      cuticular layers and prominent cuticle calcification. Morphological
      characteristics of exoskeleton renewal in marsupial manca are described.
      Elaborated cuticle in marsupial larvae indicates the importance of the
      exoskeleton in protection and support of the larval body in the marsupium and
      during the release of larvae in the external environment. 

PMID- 25051212
TI  - Observation of vibrational energy exchange in a type-III antifreeze protein.
AB  - We performed time- and polarization-resolved pump-probe and two-dimensional
      infrared (2D-IR) experiments to study the dynamics of the amide I vibration of a
      7 kDa type-III antifreeze protein. In the pump-probe experiments, we used
      femtosecond mid-infrared pulses to investigate the vibrational relaxation
      dynamics of the amide mode. The transient spectra show the presence of two
      spectral components that decay with different lifetimes, indicative of the
      presence of two distinct amide subbands. The 2D-IR experiments reveal the
      coupling between the two bands in the form of cross-peaks. On the basis of
      previous work by Demirdoven et al. ( J. Am. Chem. Soc. 2004 , 126 , 7981 - 7990
      ), we assign the observed bands to the two infrared-active modes alpha(-) and
      alpha(+) found in protein beta-sheets. The amplitudes of the cross-peak were
      found to increase with delay time, indicating that the cross-peaks originate from
      population transfer between the coupled amide oscillators. The time constant of
      the energy transfer was found to be 6-7 ps. 

PMID- 25051211
TI  - Transition-state analysis of 2-O-acetyl-ADP-ribose hydrolysis by human
      macrodomain 1.
AB  - Macrodomains, including the human macrodomain 1 (MacroD1), are erasers of the
      post-translational modification of monoadenosinediphospho-ribosylation and
      hydrolytically deacetylate the sirtuin product O-acetyl-ADP-ribose (OAADPr).
      OAADPr has been reported to play a role in cell signaling based on oocyte
      microinjection studies, and macrodomains affect an array of cell processes
      including transcription and response to DNA damage. Here, we investigate human
      MacroD1 by transition-state (TS) analysis based on kinetic isotope effects (KIEs)
      from isotopically labeled OAADPr substrates. Competitive radiolabeled-isotope
      effects and mass spectrometry were used to obtain KIE data to yield intrinsic KIE
      values. Intrinsic KIEs were matched to a quantum chemical structure of the TS
      that includes the active site residues Asp184 and Asn174 and a structural water
      molecule. Transition-state analysis supports a concerted mechanism with an early
      TS involving simultaneous nucleophilic water attack and leaving group bond
      cleavage where the breaking C-O ester bond=1.60 A and the C-O bond to the
      attacking water nucleophile=2.30 A. The MacroD1 TS provides mechanistic
      understanding of the OAADPr esterase chemistry.

PMID- 25051213
TI  - Gene expression, function, and diversity of Nkx2-4 in the rainbow trout,
      Oncorhynchus mykiss.
AB  - Nkx2 homeodomain transcription factors are involved in various developmental
      processes and cell specification: e.g. in mammals, NKX2-1 is essential for
      thyroid-specific gene expression and thyroid morphogenesis. Among Nkx2 proteins,
      information is still very limited for Nkx2-4. In the present study, we have
      identified three distinct cDNAs encoding Nkx2-4 isoforms (Nkx2-4a, -b, and -c)
      from the rainbow trout thyroid tissue, and characterized their transcriptional
      properties. The trout Nkx2-4 proteins were all predicted to conserve three
      characteristic domains: the tinman-like amino terminal decapeptide, the NK2
      homeodomain, and the NK2-specific domain, and also share 75-89% amino acid
      similarity. It was shown by dual luciferase assay that Nkx2-4a and Nkx2-4b, but
      not Nkx2-4c, significantly activated transcription from a cotransfected rat
      thyroglobulin (TG) promoter. An electrophoretic mobility shift assay indicated
      that all the Nkx2-4 isoforms could bind to the TG promoter, implying that the
      faint transcriptional activity of Nkx2-4c might result from some critical amino
      acid substitution(s) outside the homeodomain. RT-PCR analysis revealed similar
      tissue distribution patterns for Nkx2-4a and Nkx2-4b mRNAs. Both mRNAs were
      expressed abundantly in the thyroid, and weakly in the testis. On the other hand,
      Nkx2-4c mRNA was detected in the ovary as well as in the thyroid. The expression
      sites of Nkx2-4c mRNA were localized, by in situ hybridization histochemistry, to
      the ovarian granulosa cells and to the thyroid follicular cells. The results
      suggest that in the rainbow trout, Nkx2-4a and Nkx2-4b might play a major role in
      TG gene transcription whereas Nkx2-4c might have some functions in the ovary as
      well as the thyroid. 

PMID- 25051214
TI  - Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine
      carcinoma.
AB  - A 71-year-old female with a known history of primary hepatic neuroendocrine
      carcinoma, presented with a visual defect, proptosis and restricted eye movements
      of the right eye. Biopsies from the orbit and from the primary hepatic
      neuroendocrine carcinoma showed similar morphological and immunohistochemical
      features, and high-resolution, array-based comparative genomic hybridization
      demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both
      in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The
      orbital mass was diagnosed as a metastasis from the primary hepatic
      neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely
      rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma
      metastasis. This is the first reported case of an orbital metastasis with origin
      from a primary hepatic neuroendocrine carcinoma. 

PMID- 25051215
TI  - Application of a solar UV/chlorine advanced oxidation process to oil sands
      process-affected water remediation.
AB  - The solar UV/chlorine process has emerged as a novel advanced oxidation process
      for industrial and municipal wastewaters. Currently, its practical application to
      oil sands process-affected water (OSPW) remediation has been studied to treat
      fresh OSPW retained in large tailings ponds, which can cause significant adverse
      environmental impacts on ground and surface waters in Northern Alberta, Canada.
      Degradation of naphthenic acids (NAs) and fluorophore organic compounds in OSPW
      was investigated. In a laboratory-scale UV/chlorine treatment, the NAs
      degradation was clearly structure-dependent and hydroxyl radical-based. In terms
      of the NAs degradation rate, the raw OSPW (pH ~ 8.3) rates were higher than those
      at an alkaline condition (pH = 10). Under actual sunlight, direct solar
      photolysis partially degraded fluorophore organic compounds, as indicated by the
      qualitative synchronous fluorescence spectra (SFS) of the OSPW, but did not
      impact NAs degradation. The solar/chlorine process effectively removed NAs (75
      84% removal) and fluorophore organic compounds in OSPW in the presence of 200 or
      300 mg L(-1) OCl(-). The acute toxicity of OSPW toward Vibrio fischeri was
      reduced after the solar/chlorine treatment. However, the OSPW toxicity toward
      goldfish primary kidney macrophages after solar/chlorine treatment showed no
      obvious toxicity reduction versus that of untreated OSPW, which warrants further
      study for process optimization. 

PMID- 25051216
TI  - Delivery of treatment for hepatitis C virus infection in the primary care
      setting.
AB  - OBJECTIVES: The aim of this study was to evaluate the feasibility, safety and
      efficacy of treatment for chronic hepatitis C virus (HCV) infection through a
      primary care-based model for the delivery of HCV services in New South Wales
      (NSW), Australia. PARTICIPANTS AND METHODS: This observational cohort study
      recruited participants through seven primary care clinics in NSW, Australia,
      between November 2010 and June 2013. Patients with HCV genotype 2/3 were treated
      without specialist review, whereas those with genotype 1 required an initial
      specialist review. Treatment consisted of pegylated interferon-alpha-2a/2b and
      ribavirin. Sustained virological response and adverse events were evaluated.
      RESULTS: Among 41 participants (mean age 44 years, 73% men) initiating treatment
      with pegylated interferon-alpha-2a/2b and ribavirin, 90% had injected drugs ever,
      16% had injected drugs in the past 30 days and 56% had ever received opioid
      substitution treatment. HCV genotype 1 and genotype 2/3 occurred in 17% (n=7) and
      83% (n=34). Treatment was completed in 83% (34 of 41), with seven
      discontinuations [adverse event (depression), n=1; patient decision, n=1; lost to
      follow-up, n=3; virological nonresponse, n=2]. In an intent-to-treat analysis,
      sustained virological response was 71% overall (29 of 41), 43% in genotype 1
      (three of seven) and 76% in genotype 2/3 (26 of 34). CONCLUSION: Initiation of
      HCV treatment in the primary care setting is an effective alternative for
      selected patients and may contribute towards increasing access to HCV care.

PMID- 25051217
TI  - Does the extent of lymphadenectomy, number of lymph nodes, positive lymph node
      ratio and neutrophil-lymphocyte ratio impact surgical outcome of perihilar
      cholangiocarcinoma?
AB  - BACKGROUND: Lymph node (LN) status is an important predictor of survival
      following resection of perihilar cholangiocarcinoma (PHCCA). Controversies still
      exist with regard to the prognostic value of optimum extent of lymphadenectomy,
      total number of nodes removed, LN ratio (LNR) and neutrophil-lymphocyte ratio
      (NLR) on overall survival (OS) and disease-free survival (DFS) following PHCCA
      resection. METHODS: From 1994 to 2010, 84 PHCCAs were resected; 78 are included
      in this analysis. Kaplan-Meier survival curves were studied using log-rank
      statistics to assess which variables affected OS and DFS. The variables that
      showed statistical significance (P<0.05) on Kaplan-Meier univariate analysis were
      subjected to multivariate analysis using Cox proportional hazards model. RESULTS:
      Five-year OS for node-positive status (n=45) was 10%, whereas node-negative
      (n=33) OS was 41% (P<0.001). Similarly, 5-year DFS was worse in the node-positive
      group (8%) than in the node-negative group (36%, P=0.001). There was no
      difference in 5-year OS (31 vs. 12%, P=0.135) and DFS (22 vs. 16%, P=0.518)
      between those with regional lymphadenectomy and those who underwent regional plus
      para-aortic lymphadenectomy, respectively. On univariate analysis, patients with
      20 or more LNs removed had worse 5-year OS (0%) when compared with those with
      less than 20 LNs removed (29%, P=0.047). Moderate/poor tumour differentiation,
      distant metastasis and LN involvement were independent predictors of OS. Positive
      LNR had no effect on OS. Vascular invasion and an LNR of at least 0.37 were
      independent predictors of DFS. NLR had no effect on OS and DFS. CONCLUSION:
      Extended lymphadenectomy patients (>=20 LNs) had worse OS when compared with
      those with more limited (<20 LNs) resection. An LNR of at least 0.37 is an
      independent predictor of DFS.

PMID- 25051218
TI  - Transient elastography, APRI, and ultrasound have minimal utility in chronic low
      replicative hepatitis B infection.
AB  - BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is a significant cause of
      morbidity and mortality. E-antigen-negative CHB patients, with low liver enzymes
      and viremia, generally fare better. We determined the proportion of chronic low
      replicative hepatitis B patients not meeting guideline-based antiviral therapy
      criteria nonetheless requiring treatment and increased hepatocellular carcinoma
      and varices surveillance based on transient elastography (TE), aspartate
      aminotransferase-to-platelet ratio index (APRI), and/or ultrasound (US) findings.
      MATERIALS AND METHODS: The Ottawa Hospital Viral Hepatitis Database was utilized.
      Included CHB patients were observed from January 2011 to April 2013, who were at
      least 18 years of age, e-antigen negative, with hepatitis B virus (HBV) DNA
      levels below 20,000 IU/ml, normal liver enzymes (alanine transaminase <64 U/l),
      and normal synthetic function. Patients with other liver diseases, HIV, or HBV
      antiviral use were excluded. TE and US results were recorded and APRI was
      calculated. RESULTS: A total of 264 patients met the eligibility criteria and 79
      underwent TE. The median age was 41 years (quartiles: 37, 49); 53% were male
      patients and 95% were immigrants. Races included 47% Southeast Asians, 37% Black,
      and 11% White. Mean alanine transaminase and aspartate aminotransferase were 34
      U/l (SD 13) and 21 U/l (SD 7), respectively. The mean HBV DNA level was 2.15*10
      IU/ml. The mean TE score was 4.5 kPa (SD 1.1). One patient had F2 fibrosis by TE.
      All others were F0-F1. The mean APRI was 0.30 (SD 0.20) with no values greater
      than 1.5. CONCLUSION: No patients were identified with advanced fibrosis by TE,
      APRI, or US meriting HBV antiviral therapy and/or enhanced screening. TE and US
      have minimal apparent utility in this specific population.

PMID- 25051219
TI  - Cause-specific mortality associated with aging in patients with hepatocellular
      carcinoma undergoing percutaneous radiofrequency ablation.
AB  - OBJECTIVE: The number of elderly patients diagnosed with hepatocellular carcinoma
      (HCC) is expected to increase. The aim of this study is to evaluate the efficacy
      of radiofrequency ablation (RFA) in elderly patients with HCC and to investigate
      cause-specific excess deaths associated with increasing number of elderly
      patients. MATERIALS AND METHODS: We enrolled 1401 naive patients with HCC who
      were treated initially by RFA from 1999 to 2011. Patients below 75 years of age
      were categorized as 'younger' and those at least 75 as 'elderly'. Differences in
      the demographic and laboratory data of these patients were assessed, along with
      Kaplan-Meier analysis of survival using the log-rank test. In addition, we
      assessed the causes of death, defined as liver related and liver unrelated, by
      competing risk analysis and risk factors for respective causes of death by a
      proportional subdistribution model. RESULTS: Overall, 353 patients were
      categorized as elderly. Elderly patients were more likely to be women, infected
      with hepatitis C virus, and score better in the Child-Pugh classification. The
      mortality at 5 years was lower in the elderly than in the younger patients (47.3
      vs. 37.1%; P<0.001). Competing risk analysis showed a significant difference in
      liver-unrelated death (P<0.001) between the two groups, whereas there were no
      significant differences in liver-related death (P=0.64). By the proportional
      subdistribution model, age was a significant risk factor only for liver-unrelated
      death. CONCLUSION: RFA provided satisfactory 5-year survival rates in elderly
      patients with HCC. The elderly tended to die from liver-unrelated causes.

PMID- 25051220
TI  - Use of fundus autofluorescence to evaluate retinal artery occlusions.

PMID- 25051222
TI  - Synthetic turn mimetics and hairpin nucleators: Quo Vadimus?
AB  - Structural mimicry of peptides has witnessed perceptible progress in the last
      three decades. Reverse turn and beta-hairpin units are the smallest secondary
      structural motifs that are some of the most scrutinized functional cores of
      peptides and proteins. The practice of mimicking, without altering the function
      of the bioactive core, ranges from conformational locking of the basic skeleton
      to total replacement of structural architecture using synthetic analogues.
      Development of heterogeneous backbones--using unnatural residues in place of
      natural ones--has broadened further opportunities for efficient structural
      rigidification. This feature article endeavours to trail the path of progress
      achieved hitherto and envisage the possibilities that lie ahead in the
      development of synthetic turn mimetics and hairpin nucleators.

PMID- 25051221
TI  - Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large
      and highly aggressive triple negative breast tumors.
AB  - There is an unmet need for efficient near-infrared photothermal transducers for
      the treatment of highly aggressive cancers and large tumors where the penetration
      of light can be substantially reduced, and the intra-tumoral nanoparticle
      transport is restricted due to the presence of hypoxic or necrotic regions. We
      report the performance advantages obtained by sub 100nm gold nanomatryushkas,
      comprising concentric gold-silica-gold layers compared to conventional ~150nm
      silica core gold nanoshells for photothermal therapy of triple negative breast
      cancer. We demonstrate that a 33% reduction in silica-core-gold-shell
      nanoparticle size, while retaining near-infrared plasmon resonance, and keeping
      the nanoparticle surface charge constant, results in a four to five fold tumor
      accumulation of nanoparticles following equal dose of injected gold for both
      sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive
      triple negative breast tumors is doubled for the nanomatryushka treatment group
      under identical photo-thermal therapy conditions. The higher absorption cross
      section of a nanomatryoshka results in a higher efficiency of photonic to thermal
      energy conversion and coupled with 4-5* accumulation within large tumors results
      in superior therapy efficacy. 

PMID- 25051223
TI  - [Silver(I)(pyridine-containing ligand)] complexes as unusual catalysts for A(3)
      coupling reactions.
AB  - Two original macrocyclic silver(I)(pyridine-containing ligand) complexes
      [Ag(I)(Pc-L)] were synthesized and characterized. Their ability to catalyze the
      coupling among aldehydes, terminal alkynes and amines (A(3)-coupling) was
      demonstrated. The reaction could be performed under conventional as well as
      dielectric heating. The catalysts were effective in both cases, but dielectric
      heating allowed a lower catalyst loading and reduced ratio among reaction
      partners in shorter reaction times. The reaction scope was broad, including
      aryl/alkyl aldehydes, aryl/alkyl acetylenes and secondary aliphatic amines. Some
      unprecedented propargylamines have been prepared. The new catalytic system was
      also tested with more challenging coupling partners such as aniline and ketones. 

PMID- 25051224
TI  - Mitochondrial DNA control region analysis of three ethnic groups in the Republic
      of Macedonia.
AB  - A total of 444 individuals representing three ethnic groups (Albanians, Turks and
      Romanies) in the Republic of Macedonia were sequenced in the mitochondrial
      control region. The mtDNA haplogroup composition differed between the three
      groups. Our results showed relatively high frequencies of haplogroup H12 in
      Albanians (8.8%) and less in Turks (3.3%), while haplogroups M5a1 and H7a1a were
      dominant in Romanies (13.7% and 10.3%, respectively) but rare in the former two.
      This highlights the importance of regional sampling for forensic mtDNA databasing
      purposes. These population data will be available on EMPOP under accession
      numbers EMP00644 (Albanians), EMP00645 (Romanies) and EMP00646 (Turks). 

PMID- 25051225
TI  - Exploring iris colour prediction and ancestry inference in admixed populations of
      South America.
AB  - New DNA-based predictive tests for physical characteristics and inference of
      ancestry are highly informative tools that are being increasingly used in
      forensic genetic analysis. Two eye colour prediction models: a Bayesian
      classifier - Snipper and a multinomial logistic regression (MLR) system for the
      Irisplex assay, have been described for the analysis of unadmixed European
      populations. Since multiple SNPs in combination contribute in varying degrees to
      eye colour predictability in Europeans, it is likely that these predictive tests
      will perform in different ways amongst admixed populations that have European co
      ancestry, compared to unadmixed Europeans. In this study we examined 99
      individuals from two admixed South American populations comparing eye colour
      versus ancestry in order to reveal a direct correlation of light eye colour
      phenotypes with European co-ancestry in admixed individuals. Additionally, eye
      colour prediction following six prediction models, using varying numbers of SNPs
      and based on Snipper and MLR, were applied to the study populations. Furthermore,
      patterns of eye colour prediction have been inferred for a set of publicly
      available admixed and globally distributed populations from the HGDP-CEPH panel
      and 1000 Genomes databases with a special emphasis on admixed American
      populations similar to those of the study samples. 

PMID- 25051227
TI  - A DFT study on the interaction between glycine molecules/radicals and the (8, 0)
      SiCNT.
AB  - The geometrical structures, energetics and electronic properties of glycine
      molecules as well as dehydrogenated radical interaction with silicon carbide
      nanotubes (SiCNTs) are investigated based on density functional theory (DFT) for
      the first time. Different from the weak adsorption on CNTs, it is shown that
      glycine molecules tend to be chemisorbed onto SiCNTs. There are three patterns of
      the individual glycine molecule adsorbed on the (8, 0) SiCNT, including
      monodentate, cycloaddition and dissociative ones, with the latter two patterns
      (Eads ranges from -22.08 to -34.99 kcal mol(-1)) more stable than the monodentate
      one (Eads ranges from -8.16 to -21.14 kcal mol(-1)). In addition, we also
      investigated the adsorption of multiple glycine molecules on various zigzag (n,
      0) (n = 7, 8, 9 and 10) SiCNTs. It is shown that totally n (n = 7, 8, 9 and 10)
      molecules can be chemisorbed on one circle of the wall of the SiCNT at most. And
      the Eads per glycine decreases gradually with the increasing tube diameter due to
      the curvature effects. For the adsorption of dehydrogenated glycine radicals, it
      is found that both the N-centered and C-centered ones can form stable complexes
      by attacking the (8, 0) SiCNT. Totally one monodentate and two bidentate
      adsorption configurations of the N-centered radical and three monodentate
      configurations of the C-centered one can be found. Note that the important half
      metals can be obtained for the bidentate configurations from the N-centered
      radical due to the hybridization state of the radical and the tube in one spin
      channel crossing the Fermi level, while the p-type semiconductor can be produced
      for the monodentate configurations from the C-centered radical because the
      impurity state derived from the radical itself is closer to the edge of the
      valence band above the Fermi level, which may be applied in building electronic
      devices and metal-free catalysis. Finally, we found that the encapsulation of the
      glycine molecule is exothermic and thus energetically favourable in the SiCNTs
      with the diameter larger than the (9, 0) SiCNT. The present study is expected to
      create promising applications in nano-device building and biotechnology. 

PMID- 25051226
TI  - Development and assessment of an optimized next-generation DNA sequencing
      approach for the mtgenome using the Illumina MiSeq.
AB  - The development of molecular tools to detect and report mitochondrial DNA (mtDNA)
      heteroplasmy will increase the discrimination potential of the testing method
      when applied to forensic cases. The inherent limitations of the current state-of
      the-art, Sanger-based sequencing, including constrictions in speed, throughput,
      and resolution, have hindered progress in this area. With the advent of next
      generation sequencing (NGS) approaches, it is now possible to clearly identify
      heteroplasmic variants, and at a much lower level than previously possible.
      However, in order to bring these approaches into forensic laboratories and
      subsequently as accepted scientific information in a court of law, validated
      methods will be required to produce and analyze NGS data. We report here on the
      development of an optimized approach to NGS analysis for the mtDNA genome
      (mtgenome) using the Illumina MiSeq instrument. This optimized protocol allows
      for the production of more than 5 gigabases of mtDNA sequence per run, sufficient
      for detection and reliable reporting of minor heteroplasmic variants down to
      approximately 0.5-1.0% when multiplexing twelve samples. Depending on sample
      throughput needs, sequence coverage rates can be set at various levels, but were
      optimized here for at least 5000 reads. In addition, analysis parameters are
      provided for a commercially available software package that identify the highest
      quality sequencing reads and effectively filter out sequencing-based noise. With
      this method it will be possible to measure the rates of low-level heteroplasmy
      across the mtgenome, evaluate the transmission of heteroplasmy between the
      generations of maternal lineages, and assess the drift of variant sequences
      between different tissue types within an individual. 

PMID- 25051229
TI  - Renal denervation using catheter-based radiofrequency ablation with temperature
      control: renovascular safety profile and underlying mechanisms in a hypertensive
      canine model.
AB  - OBJECTIVE: Renal denervation is a novel method for hypertension treatment. In
      this study, we aimed to investigate the safety and efficacy of radiofrequency
      ablation (RFA) at ablation temperatures of 45  degrees C or 50  degrees C and its
      possible mechanisms. METHODS: A hypertensive canine model was established by
      abdominal aortic constriction in 20 healthy hybrid dogs. These dogs were then
      randomly assigned to the treatment and the control groups, with dogs in the
      treatment group further randomly assigned to receive RFA at ablation temperatures
      of 45  degrees C or 50  degrees C. In the treatment group, RFA was performed at 1
      month after modeling; renal angiography was performed at 2 months after ablation.
      The arterial vessels of the dogs were examined histologically with hematoxylin
      and eosin staining. Changes in blood pressure in the foreleg and whole-body
      norepinephrine spillover rate were also assessed. RESULTS: No arterial stenosis,
      dissection, thrombosis or other abnormalities were detected in the treated
      vessels by renal angiography, yet histology results showed minimal to mild renal
      arterial injury. Renal denervation resulted in a marked decrease in the whole
      body norepinephrine spillover rate (p < 0.05) in addition to significantly
      reducing blood pressure (p < 0.05), with no significant differences detected
      between the 45  degrees C and 50  degrees C subgroups for both (p > 0.05).
      CONCLUSION: Renal denervation can be performed without acute major adverse
      events, using catheter-based RFA with temperature control. The procedure was
      feasible in reducing blood pressure by at least partially inhibiting sympathetic
      drive and systemic sympathetic outflow.

PMID- 25051230
TI  - Red wine extract decreases pro-inflammatory markers, nuclear factor-kappaB and
      inducible NOS, in experimental metabolic syndrome.
AB  - We aimed to analyse the effects of alcohol-free Alibernet red wine extract (AWE)
      on nitric oxide synthase (NOS) activity and pro-inflammatory markers such as
      nuclear factor-kappaB (NFkappaB) and inducible NOS (iNOS) protein expression in
      experimental metabolic syndrome. Young 6 week-old male Wistar Kyoto (WKY) and
      obese, spontaneously hypertensive rats (SHR/N-cp) were divided into control
      groups and groups treated with AWE (24.2 mg per kg per day) for 3 weeks (n = 6 in
      each group). Total NOS activity and endothelial NOS (eNOS), iNOS and NFkappaB
      (p65) protein expressions were determined in the heart left ventricle and aorta
      by Western blot and immunohistochemical analysis. All parameters investigated
      significantly increased in the aorta of SHR/N-cp rats. Pro-inflammatory markers
      such as NFkappaB and iNOS were increased in the left ventricle as well. AWE
      treatment did not affect total NOS activity and eNOS expression in the aorta;
      however, it was able to decrease NFkappaB and iNOS protein expression in both the
      left ventricle and aorta. In conclusion, in the cardiovascular system, Alibernet
      red wine extract decreased NFkappaB and iNOS protein expressions elevated as a
      consequence of developed metabolic syndrome. This effect may represent one of the
      protective, anti-inflammatory properties of Alibernet red wine polyphenols on
      cardiovascular risk factors related to metabolic syndrome. 

PMID- 25051231
TI  - Cholesterol synthesis inhibitor RO 48-8071 suppresses transcriptional activity of
      human estrogen and androgen receptor.
AB  - Breast cancer cells express enzymes that convert cholesterol, the synthetic
      precursor of steroid hormones, into estrogens and androgens, which then drive
      breast cancer cell proliferation. In the present study, we sought to determine
      whether oxidosqualene cyclase (OSC), an enzyme in the cholesterol biosynthetic
      pathway, may be targeted to suppress progression of breast cancer cells. In
      previous studies, we showed that the OSC inhibitor RO 48-8071 (RO) may be a
      ligand which could potentially be used to control the progression of estrogen
      receptor-alpha (ERalpha)-positive breast cancer cells. Herein, we showed, by real
      time PCR analysis of mRNA from human breast cancer biopsies, no significant
      differences in OSC expression at various stages of disease, or between tumor and
      normal mammary cells. Since the growth of hormone-responsive tumors is ERalpha
      dependent, we conducted experiments to determine whether RO affects ERalpha.
      Using mammalian cells engineered to express human ERalpha or ERbeta protein,
      together with an ER-responsive luciferase promoter, we found that RO dose
      dependently inhibited 17beta-estradiol (E2)-induced ERalpha responsive luciferase
      activity (IC50 value, ~10 uM), under conditions that were non-toxic to the cells.
      RO was less effective against ERbeta-induced luciferase activity. Androgen
      receptor (AR) mediated transcriptional activity was also reduced by RO. Notably,
      while ERalpha activity was reduced by atorvastatin, the HMG-CoA reductase
      inhibitor did not influence AR activity, showing that RO possesses broader
      antitumor properties. Treatment of human BT-474 breast cancer cells with RO
      reduced levels of estrogen-induced PR protein, confirming that RO blocks ERalpha
      activity in tumor cells. Our findings demonstrate that an important means by
      which RO suppresses hormone-dependent growth of breast cancer cells is through
      its ability to arrest the biological activity of ERalpha. This warrants further
      investigation of RO as a potential therapeutic agent for use against hormone
      dependent breast cancers. 

PMID- 25051232
TI  - Strain engineering in monolayer materials using patterned adatom adsorption.
AB  - We utilize reactive empirical bond order (REBO)-based interatomic potentials to
      explore the potential for the engineering of strain in monolayer materials using
      lithographically or otherwise patterned adatom adsorption. In the context of
      graphene, we discover that the monolayer strain results from a competition
      between the in-plane elasticity and out-of-plane relaxation deformations. For
      hydrogen adatoms on graphene, the strain outside the adsorption region vanishes
      due to out-of-plane relaxation deformations. Under some circumstances, an annular
      adsorption pattern generates homogeneous tensile strains of approximately 2% in
      graphene inside the adsorption region, approximately 30% of the strain in the
      adsorbed region. We find that an elliptical adsorption pattern produces strains
      of as large as 5%, close to the strain in the adsorbed region. Also, nonzero
      maximum shear strain (~ 4%) can be introduced by the elliptical adsorption
      pattern. We find that an elastic plane stress model provides qualitative guidance
      for strain magnitudes and conditions under which strain-diminishing buckling can
      be avoided. We identify geometric conditions under which this effect has
      potential to be scaled to larger areas. Our results elucidate a method for strain
      engineering at the nanoscale in monolayer devices.

PMID- 25051233
TI  - Biomarkers identified by urinary metabonomics for noninvasive diagnosis of
      nutritional rickets.
AB  - Nutritional rickets is a worldwide public health problem; however, the current
      diagnostic methods retain shortcomings for accurate diagnosis of nutritional
      rickets. To identify urinary biomarkers associated with nutritional rickets and
      establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra
      performance liquid chromatography/quadrupole time-of-flight tandem mass
      spectrometry and multivariate statistical analysis were employed to investigate
      the metabolic alterations associated with nutritional rickets in 200 children
      with or without nutritional rickets. The pathophysiological changes and
      pathogenesis of nutritional rickets were illustrated by the identified
      biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets
      were identified and five candidate biomarkers for clinical diagnosis were
      screened and identified by quantitative analysis and receiver operating curve
      analysis. Urinary levels of five candidate biomarkers were measured using mass
      spectrometry or commercial kits. In the validation step, the combination of
      phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic
      with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis
      of the pathway analysis of biomarkers, our urinary metabonomics analysis gives
      new insight into the pathogenesis and pathophysiology of nutritional rickets. 

PMID- 25051235
TI  - Aquatic toxicity of the macrolide antibiotic clarithromycin and its metabolites.
AB  - The human macrolide antibiotic clarithromycin is widespread in surface waters.
      Our study shows that its major metabolite 14-hydroxy(R)-clarithromycin is found
      in surface waters in comparable amounts. This metabolite is known to be
      pharmacologically active. Additionally, clarithromycin is partly metabolised to N
      desmethyl-clarithromycin, which has no antimicrobial activity. For
      clarithromycin, some ecotoxicological studies on aquatic organisms have been
      published. However, many of them are not conform with the scientific principles
      as given in the "Technical guidance for deriving environmental quality standards"
      (TGD-EQS), because numerous studies were poorly documented and the methods did
      not contain analytical measurements confirming that the exposure concentrations
      were in the range of +/- 20% of the nominal concentrations. Ecotoxicological
      effects of clarithromycin and its two metabolites on the zebrafish Danio rerio
      (embryo test), the microcrustacean Daphnia magna, the aquatic monocotyledonous
      macrophyte Lemna minor, the freshwater green alga Desmodesmus subspicatus
      (Chlorophyta) and the cyanobacterium Anabaena flosaquae were investigated in
      compliance with the TGD-EQS. Environmental risk assessment was performed using
      ErC10 values of Anabaena, the species most sensitive to clarithromycin and 14
      hydroxy(R)-clarithromycin in our testing. Based oncomparable toxicity and similar
      concentrations of clarithromycin and its active metabolite 14-hydroxy(R)
      clarithromycin in surface waters, an additional multiplication factor of 2 to the
      assessment factor of 10 on the ErC10 of clarithromycin should be used.
      Consequently, a freshwater quality standard of 0.130 MUg L(-1) is proposed for
      clarithromycin as the "lead substance". Taking this additional multiplication
      factor of 2 into account, single monitoring of clarithromycin may be sufficient,
      in order to reduce the number of substances listed for routine monitoring
      programs.

PMID- 25051234
TI  - Intracellular clusterin interacts with brain isoforms of the bridging integrator
      1 and with the microtubule-associated protein Tau in Alzheimer's disease.
AB  - Sporadic or late-onset Alzheimer's disease (AD) is expected to affect 50% of
      individuals reaching 85 years of age. The most significant genetic risk factor
      for late-onset AD is the e4 allele of APOE gene encoding apolipoprotein E, a
      lipid carrier shown to modulate brain amyloid burden. Recent genome-wide
      association studies have uncovered additional single nucleotide polymorphisms
      (SNPs) linked to AD susceptibility, including those in the CLU and BIN1 genes
      encoding for clusterin (CLU) and the bridging integrator 1 (BIN1) proteins,
      respectively. Because CLU has been implicated in brain amyloid-beta (Abeta)
      clearance in mouse models of amyloid deposition, we sought to investigate whether
      an AD-linked SNP in the CLU gene altered Abeta42 biomarker levels in the
      cerebrospinal fluid (CSF). Instead, we found that the CLU rs11136000 SNP modified
      CSF levels of the microtubule-associated protein Tau in AD patients. We also
      found that an intracellular form of CLU (iCLU) was upregulated in the brain of
      Tau overexpressing Tg4510 mice, but not in Tg2576 amyloid mouse model. By
      overexpressing iCLU and Tau in cell culture systems we discovered that iCLU was a
      Tau-interacting protein and that iCLU associated with brain-specific isoforms of
      BIN1, also recently identified as a Tau-binding protein. Through expression
      analysis of CLU and BIN1 variants, we found that CLU and BIN1 interacted via
      their coiled-coil motifs. In co-immunoprecipitation studies using human brain
      tissue, we showed that iCLU and the major BIN1 isoform expressed in neurons were
      associated with modified Tau species found in AD. Finally, we showed that
      expression of certain coding CLU variants linked to AD risk led to increased
      levels of iCLU. Together, our findings suggest that iCLU and BIN1 interaction
      might impact Tau function in neurons and uncover potential new mechanisms
      underlying the etiology of Tau pathology in AD. 

PMID- 25051236
TI  - Effect of copper ions on the degradation of thiram in aqueous solution:
      identification of degradation products by HPLC-MS/MS.
AB  - The aim of this work was to examine the effect of Cu(II) on the degradation of
      thiram (Thi) in aqueous solutions, since the literature focused on this effect is
      scarce and copper based fungicides can be applied together with thiram or during
      the same season to agricultural crops. The effect of Cu(II) on the degradation of
      thiram was followed by both UV-vis and HPLC-MS/MS. When thiram is dissolved in
      pure water its degradation occurs very slowly, being negligible during the first
      7 days. However, the presence of Cu(II) has a strong influence on the thiram
      degradation in aqueous solutions along time. In the presence of an excess of
      Cu(II), a [CuThi](2+) complex is initially formed which degrades into a complex
      formed between the dimethyldithiocarbamate anion (DMDTC) and Cu(II) ion,
      [Cu(DMDTC)](+). This complex further degrades leading to other copper complexes
      which were identified for the first time, by MS(n). The results obtained in the
      present work also demonstrated that a redox reaction involving DMDTC anions and
      Cu(II) ions gives rise to the formation of a Thi-Cu(I) complex. Finally, some of
      the complexes resulting from the degradation of [CuThi](2+) are quite persistent
      in solution for long periods of time (>1 month). 

PMID- 25051237
TI  - A comprehensive assessment of human exposure to phthalates from environmental
      media and food in Tianjin, China.
AB  - A total of 448 samples including foodstuffs (rice, steamed bun, vegetables, meat,
      poultry, fish, milk and fruits), ambient PM10, drinking water, soil, indoor PM10
      and indoor dust samples from Tianjin were obtained to determine the distribution
      of six priority phthalates (PAEs) and assess the human exposure to them. The
      results indicated that DBP and DEHP were the most frequently detected PAEs in
      these samples. The concentrations of PAEs in environmental media were higher than
      those in food. We estimated the daily intake (DI) of PAEs via ingestion,
      inhalation and dermal absorption from five sources (food, water, air, dust and
      soil). Dietary intake was the main exposure source to DEP, BBP, DEHP and DOP,
      whereas water ingestion/absorption was the major source of exposure to DBP, DEHP
      and DOP. Although food and water were the overwhelmingly predominant sources of
      PAEs intake by Tianjin population, contaminated air was another important source
      of DMP, DEP and DBP contributing to up to 45% of the exposure. The results of
      this study will help in understanding the major pathways of human exposure to
      PAEs. These findings also suggest that human exposure to phthalate esters via the
      environment should not be overlooked. 

PMID- 25051238
TI  - Combined effects of two antibiotic contaminants on Microcystis aeruginosa.
AB  - Combined toxicity of spiramycin and amoxicillin was tested in Microcystis
      aeruginosa. The respective 50% effective concentrations (EC50mix) expressed in
      toxic unit (TU) values were 1.25 and 1.83 for spiramycin and amoxicillin mixed at
      1:7 and 1:1, suggesting an antagonistic interaction at the median effect level.
      Deviations from the prediction of concentration addition (CA) and independent
      action (IA) models further indicated that combined toxicity of two antibiotics
      mixed at 1:1 varied from synergism to antagonism with increasing test
      concentration. Both the EC50mix of 0.86 (in TU value) and the deviation from two
      models manifested a synergistic interaction between spiramycin and amoxicillin
      mixed at 7:1. At an environmentally relevant concentration of 800ngL(-1),
      combined effect of mixed antibiotics on algal growth changed from stimulation to
      inhibition with the increasing proportion of higher toxic component (spiramycin).
      Chlorophyll-a content and expression levels of psbA, psaB, and rbcL varied in a
      similar manner as growth rate, suggesting a correlation between algal growth and
      photosynthesis under exposure to mixed antibiotics. The stimulation of
      microcystin-production by mixed antibiotics was related with the elevated
      expression of mcyB. The mixture of two target antibiotics with low proportion of
      spiramycin (<50%) could increase the harm of M. aeruginosa to aquatic
      environments by stimulating algal growth and production and release of
      microcystin-LR at their current contamination levels. 

PMID- 25051239
TI  - Transcriptional regulation of pattern recognition receptors by Jak/STAT
      signaling, and the implications for disease pathogenesis.
AB  - Cytokines are well known for their pleiotropism, affecting a large number of
      cellular responses, including proliferation, survival, functional maturation, and
      immunomodulation. It is, therefore, not surprising that both the deregulated
      expression of cytokines and the subsequent activation of their downstream
      signaling pathways is a common feature of many cancers, as well as chronic
      inflammatory, autoimmune, metabolic, and cardiovascular diseases. In this regard,
      activation of the Janus kinase (JAK)/signal transducer and activator of
      transcription (STAT) pathway is the predominant intracellular signaling event
      triggered by cytokines, with STAT1 and STAT3 having the greatest diversity of
      biological functions among the 7 known members of the STAT family of latent
      transcription factors. Notably, over recent years, it has emerged that STAT1 and
      STAT3 are employed by various cytokines to manipulate the signal output of
      heterologous receptors of the innate immune system, namely pattern recognition
      receptors (PRRs), with both immune and nonimmune (eg, oncogenic, metabolic)
      cellular processes being affected. This review highlights these pivotal
      advancements in our understanding of how a cross talk between cytokine and PRR
      signaling networks can impact on a variety of cellular responses during disease
      pathogenesis, and the potential therapeutic implications of targeting these
      networks. 

PMID- 25051240
TI  - Evaluation of clinical and inflammatory markers of nonalcoholic fatty liver
      disease in postmenopausal women with metabolic syndrome.
AB  - BACKGROUND: The aim of this study was to assess clinical and inflammatory markers
      in nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with
      metabolic syndrome. METHODS: This cross-sectional study included 180 Brazilian
      women (age >=45 years and amenorrhea >=12 months). Metabolic syndrome was
      diagnosed by the presence of at least three of the following indicators: Waist
      circumference (WC) >88 cm, triglycerides (TGs) >=150 mg/dL, high-density
      lipoprotein (HDL) <50 mg/dL; blood pressure >=130/85 mmHg; and glucose >=100
      mg/dL. NAFLD was diagnosed by abdominal ultrasound. Participants were divided
      into three groups: Metabolic syndrome alone (n=53); metabolic syndrome+NAFLD
      (n=67); or absence of metabolic syndrome or NAFLD (control, n=60). Clinical,
      anthropometric, and biochemical variables were quantified. The inflammatory
      profile included adiponectin, interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha). Data were submitted to statistical analysis using a Tukey
      test, analysis of variance (ANOVA), chi-squared, Pearson correlation, and
      logistic regression (odds ratio, OR). RESULTS: Women with metabolic
      syndrome+NAFLD, abdominal obesity, high glucose, and insulin resistance by HOMA
      IR were compared to women with metabolic syndrome alone and controls (P<0.05).
      High values of IL-6 and TNF-alpha and low values of adiponectin were observed
      among women with metabolic syndrome alone or metabolic syndrome+NAFLD when
      compared to controls (P<0.05). In multivariate analysis, the variables considered
      as risk of NAFLD development were: High systolic blood pressure (SBP) [(OR 1.02,
      95% confidence interval (CI) 1.0-1.04]; large WC (OR 1.07, 95% CI 1.01-1.13);
      insulin resistance (OR 3.81, 95% CI 2.01-7.13); and metabolic syndrome (OR 8.68,
      95% CI 3.3-24.1). Adiponectin levels reduced NAFLD risk (OR 0.88, 95% CI 0.80
      0.96). CONCLUSION: In postmenopausal women, metabolic syndrome, abdominal
      obesity, and insulin resistance were risk markers for the development of NAFLD,
      whereas higher adiponectin values indicated a protection marker.

PMID- 25051241
TI  - Rheological studies of PMMA-PVC based polymer blend electrolytes with LiTFSI as
      doping salt.
AB  - In this research, two systems are studied. In the first system, the ratio of poly
      (methyl methacrylate) (PMMA) and poly (vinyl chloride) (PVC) is varied, whereas
      in the second system, the composition of PMMA-PVC polymer blends is varied with
      dopant salt, lithium bis (trifluoromethanesulfonyl) imide (LiTFSI) with a fixed
      ratio of 70 wt% of PMMA to 30 wt% of PVC. Oscillation tests such as amplitude
      sweep and frequency sweep are discussed in order to study the viscoelastic
      properties of samples. Elastic properties are much higher than viscous properties
      within the range in the amplitude sweep and oscillatory shear sweep studies. The
      crossover of G' and G'' is absent. Linear viscoelastic (LVE) range was further
      determined in order to perform the frequency sweep. However, the absence of
      viscous behavior in the frequency sweep indicates the solid-like characteristic
      within the frequency regime. The viscosity of all samples is found to decrease as
      shear rate increases.

PMID- 25051242
TI  - Quantitative measurement of elasticity of the appendix using shear wave
      elastography in patients with suspected acute appendicitis.
AB  - INTRODUCTION: Shear wave elastography (SWE) has not been studied for diagnosing
      appendicitis. We postulated that an inflamed appendix would become stiffer than a
      normal appendix. We evaluated the elastic modulus values (EMV) by SWE in healthy
      volunteers, patients without appendicitis, and patients with appendicitis. We
      also evaluated diagnostic ability of SWE for differentiating an inflamed from a
      normal appendix in patients with suspected appendicitis. MATERIALS AND METHODS:
      Forty-one patients with clinically suspected acute appendicitis and 11 healthy
      volunteers were prospectively enrolled. Gray-scale ultrasonography (US), SWE and
      multi-slice computed tomography (CT) were performed. The EMV was measured in the
      anterior, medial, and posterior appendiceal wall using SWE, and the highest value
      (kPa) was recorded. RESULTS: Patients were classified into appendicitis (n = 30)
      and no appendicitis groups (n = 11). One case of a negative appendectomy was
      detected. The median EMV was significantly higher in the appendicitis group (25.0
      kPa) compared to that in the no appendicitis group (10.4 kPa) or in the healthy
      controls (8.3 kPa) (p<0.001). Among SWE and other US and CT features, CT was
      superior to any conventional gray-scale US feature or SWE. Either the CT diameter
      criterion or combined three CT features predicted true positive in 30 and true
      negative in 11 cases and yielded 100% sensitivity and 100% specificity. An EMV of
      12.5 kPa for the stiffest region of the appendix predicted true positive in 28,
      true negative in 11, and false negative in two cases. The EMV (>=12.5 kPa)
      yielded 93% sensitivity and 100% specificity. CONCLUSION: Our results suggest
      that EMV by SWE helps distinguish an inflamed from a normal appendix. Given that
      SWE has high specificity, quantitative measurement of the elasticity of the
      appendix may provide complementary information, in addition to morphologic
      features on gray-scale US, in the diagnosis of appendicitis.

PMID- 25051243
TI  - Synthesis of tripeptides containing D-Trp substituted at the indole ring,
      assessment of opioid receptor binding and in vivo central antinociception.
AB  - The noncationizable tripeptide Ac-D-Trp-Phe-GlyNH2 was recently proposed as a
      novel minimal recognition motif for MU-opioid receptor. The introduction of
      different substituents (methyl, halogens, nitro, etc.) at the indole of D-Trp
      significantly influenced receptor affinities and resulted in serum stability and
      in a measurable effect on central antinociception in mice after ip
      administration.

PMID- 25051246
TI  - Chemically modified flexible strips as electrochemical biosensors.
AB  - A flexible and disposable strip sensor for non-enzymatic glucose detection is
      demonstrated in this work. The strips are prepared by using chemical modification
      processes followed by a simple electroless deposition of copper. Essentially,
      polyester overhead projector (OHP) transparent films are modified with a
      monolayer of 3-aminopropyltrimethoxysilane (APTMS) and polyaniline (PANI)
      conducting polymer. Later, nanostructured copper is deposited onto this modified
      film. Scanning electron microscope (SEM) and X-ray diffraction (XRD) studies are
      used for the structural, morphological and crystallinity characterization of the
      modified films. Electrochemical techniques, namely cyclic voltammetry (CV) and
      chronoamperometry (CA), are employed for the non-enzymatic detection of glucose.
      These studies clearly reveal the formation of homogeneous, close-packed spherical
      Cu particles converged into uniform film that exhibits a good catalytic activity
      towards the oxidation of glucose. The Cu/PANI/APTMS/OHP sensor displays a
      remarkable enhancement in the oxidation current density, a very high sensitivity
      value of 2.8456 mA cm(-2) per mM, and a linear concentration range from 100 MUM
      to 6.5 mM associated with glucose detection. Detection limit is estimated to be 5
      MUM and the response time of the sensor is determined to be less than 5 s. For
      comparison, similar studies are performed without PANI, namely Cu/APTMS/OHP films
      for glucose detection. In this case, a sensitivity value of 2.4457 mA cm(-2) per
      mM and a linear concentration range of 100 MUM-3 mM are estimated. The higher
      performance characteristics observed in the case of Cu/PANI/APTMS/OHP are
      attributed to the synergistic effects of the conducting polymer acting as an
      electron facilitator and the nanostructured Cu films. These disposable, flexible
      and low-cost strip sensors have also been applied to the detection of glucose in
      clinical blood serum samples and the results obtained agree very well with the
      actual glucose level. 

PMID- 25051245
TI  - Characterization of phosphorus in animal manures collected from three (dairy,
      swine, and broiler) farms in China.
AB  - In order to identify the phosphorus species and concentration in animal manure,
      we comparatively characterized phosphorus in dairy manure, swine manure, and
      broiler litter, using a sequential procedure, a simplified two-step procedure
      (NaHCO3/NaOH+EDTA), and a solution Phosphorus-31 Nuclear Magnetic Resonance (31P
      NMR) spectroscopy procedure. In the sequential procedure, deionized water
      extracted 39, 22, and 32%; NaHCO3 extracted 48, 26, and 37%; NaOH extracted 8, 9,
      and 13.8%; and HCl extracted 3, 42.8, and 17% of the total phosphorus in dairy
      manure, swine manure and broiler litter, respectively. Total phosphorus extracted
      by the NaHCO3/NaOH+EDTA procedure was 7.5, 32.4, and 15.8 g P kg(-1) for dairy
      manure, swine manure, and broiler litter, respectively. The solution 31P-NMR
      procedure detected that 9, 34, and 29% of total phosphorus was phytic acid in
      dairy manure, swine manure, and broiler litter, respectively. These results show
      that phosphorus forms, availability, and quantities differ between animal
      manures, which provides valuable information for P characterization of animal
      manures in China.

PMID- 25051247
TI  - Membrane tension influences the spike propagation between voltage-gated ion
      channel clusters of excitable membranes.
AB  - Ion channels of excitable membranes are known to be sensitive to various kinds of
      stimuli, but the case of simultaneous occurrence of different stimuli is poorly
      understood. Here, we theoretically analyze the influence of membrane tension on
      the dynamics of voltage-gated ion channels of excitable membranes. To do so, we
      develop a modification of the well-known Hodgkin-Huxley model to study
      numerically the spike generation and propagation in a single and two coupled
      excitable cells. We find that these cells can use membrane tension to trigger sub
      threshold spike propagation, to suppress spike propagation and to alter the
      intensity of the signal transmission. These effects indicate that cells could use
      membrane tension to regulate cell-to-cell communication. 

PMID- 25051248
TI  - Population dynamics of a Salmonella lytic phage and its host: implications of the
      host bacterial growth rate in modelling.
AB  - The prevalence and impact of bacteriophages in the ecology of bacterial
      communities coupled with their ability to control pathogens turn essential to
      understand and predict the dynamics between phage and bacteria populations. To
      achieve this knowledge it is essential to develop mathematical models able to
      explain and simulate the population dynamics of phage and bacteria. We have
      developed an unstructured mathematical model using delay-differential equations
      to predict the interactions between a broad-host-range Salmonella phage and its
      pathogenic host. The model takes into consideration the main biological
      parameters that rule phage-bacteria interactions likewise the adsorption rate,
      latent period, burst size, bacterial growth rate, and substrate uptake rate,
      among others. The experimental validation of the model was performed with data
      from phage-interaction studies in a 5 L bioreactor. The key and innovative aspect
      of the model was the introduction of variations in the latent period and
      adsorption rate values that are considered as constants in previous developed
      models. By modelling the latent period as a normal distribution of values and the
      adsorption rate as a function of the bacterial growth rate it was possible to
      accurately predict the behaviour of the phage-bacteria population. The model was
      shown to predict simulated data with a good agreement with the experimental
      observations and explains how a lytic phage and its host bacteria are able to
      coexist. 

PMID- 25051250
TI  - Laryngeal sensory neuropathy in patients with diabetes mellitus.
AB  - OBJECTIVE: To determine the prevalence of laryngeal sensory neuropathy in
      patients with type 2 diabetes mellitus. METHODS: A cross-sectional study was
      performed, comprising 50 patients diagnosed with type 2 diabetes mellitus and 36
      healthy controls. In the diabetic group, glycaemic control level, disease
      duration and presence of neuropathy were assessed. Participants were diagnosed
      with laryngeal sensory neuropathy if they had a cough, globus pharyngeus or
      throat clearing lasting for more than six weeks, in the absence of
      laryngopharyngeal reflux disease, allergies, asthma, angiotensin-converting
      enzyme inhibitor intake or psychogenic disorders. RESULTS: In the diabetic group,
      the mean age +/- standard deviation was 44.66 +/- 10.07 years. Sixty per cent of
      patients were male, 42 per cent had had diabetes for more than five years and 52
      per cent had average to poor glycaemic control. The prevalence of laryngeal
      sensory neuropathy was 42 per cent in the diabetic group, compared with 13.9 per
      cent in controls; this difference was statistically significant (p = 0.005).
      There was no association between the prevalence of laryngeal sensory neuropathy
      and glycaemic control level, disease duration or presence of neuropathy.
      CONCLUSION: Laryngeal sensory neuropathy is more common in patients with type 2
      diabetes mellitus than in controls.

PMID- 25051249
TI  - In vitro characterization of patches of human mesenchymal stromal cells.
AB  - Stem cells may represent an excellent strategy to improve the healing of skin
      ulcers. Today the administration mode of stem cells to skin defects remains
      unsatisfactory. Delivering stem cells with topical treatments represents a new
      strategy and answering the patients' need. Mesenchymal stromal cells (MSC) have
      been shown to improve wound healing of cutaneous lesions and amniotic membrane
      (AM) is known to represent a natural scaffold for cells. The aim of this study is
      to develop a tissue-engineered product combining MSC and AM for clinical use. In
      this work we investigated whether the stromal matrix of intact human AM could
      constitute a scaffold for human MSC derived from either bone marrow (BM) or
      adipose tissue (AT). For this purpose, clinical-grade AM, MSC, and culture medium
      were used. We performed experiments of short-term adherence and proliferation for
      15 days after the seeding of the cells. Morphological aspects and secretion
      profiles of MSC onto AM were studied, respectively, by scanning electron
      microscopy and Luminex analysis. Results demonstrated that the stromal matrix
      allow the adherence in much greater amount of MSC from BM or AT compared to 2D
      material. Experiments of proliferation showed that both kinds of MSC could
      proliferate on the stromal matrix and remain viable 15 days after the seeding of
      the cells. The 3D analysis of MSC culture demonstrated that both types of MSC
      invaded the stromal matrix and grew in multiple layers while retaining their
      fibroblastic morphology. By studying the secretion profile of MSC onto the
      stromal matrix, we found that both kinds of MSC secrete important cytokines and
      growth factors for wound healing of cutaneous lesions, such as vascular
      endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth
      factor. In conclusion, these results suggest that the stromal matrix of AM seeded
      with MSC represents a bioactive scaffold that should be evaluated in patients
      with a nonhealing cutaneous wound. 

PMID- 25051251
TI  - Drift diving by hooded seals (Cystophora cristata) in the Northwest Atlantic
      Ocean.
AB  - Many pinniped species perform a specific dive type, referred to as a 'drift
      dive', where they drift passively through the water column. This dive type has
      been suggested to function as a resting/sleeping or food processing dive, and can
      be used as an indication of feeding success by calculating the daily change in
      vertical drift rates over time, which reflects the relative fluctuations in
      buoyancy of the animal as the proportion of lipids in the body change. Northwest
      Atlantic hooded seals perform drift dives at regular intervals throughout their
      annual migration across the Northwest Atlantic Ocean. We found that the daily
      change in drift rate varied with geographic location and the time of year and
      that this differed between sexes. Positive changes in buoyancy (reflecting
      increased lipid stores) were evident throughout their migration range and
      although overlapping somewhat, they were not statistically associated with high
      use areas as indicated by First Passage Time (FPT). Differences in the seasonal
      fluctuations of buoyancy between males and females suggest that they experience a
      difference in patterns of energy gain and loss during winter and spring,
      associated with breeding. The fluctuations in buoyancy around the moulting period
      were similar between sexes. 

PMID- 25051253
TI  - Tag/hybridization-based sensitive detection of polymerase chain reaction
      products.
AB  - The polymerase chain reaction (PCR) is an important technology to amplify a
      single copy or a few copies of DNA segment in genomic DNAs, visualizing the
      segment as DNA fragment. Thus, PCR is frequently used in various examinations
      such as detection of bacteria and fungi in the food industry. Here, we report a
      simple and sensitive method for detection of PCR products using single-strand tag
      sequence and hybridization of the tag sequence to the complementary tag sequence
      immobilized on solid material (STH). The detection sensitivity was found to be at
      least 50 times higher than electrophoresis/ethidium bromide (EtBr) visualization
      for approximately a 500-bp fragment and higher than the ordinary hybridization,
      that is, hybridization of denatured PCR product to probe sequence immobilized on
      solid material. 

PMID- 25051254
TI  - Quantitative spectral comparison by weighted spectral difference for protein
      higher order structure confirmation.
AB  - Previously, different approaches of spectral comparison were evaluated, and the
      spectral difference (SD) method was shown to be valuable for its linearity with
      spectral changes and its independence on data spacing (Anal. Biochem. 434 (2013)
      153-165). In this note, we present an enhancement of the SD calculation, referred
      to as the "weighted spectral difference" (WSD), by implementing a weighting
      function based on relative signal magnitude. While maintaining the advantages of
      the SD method, WSD improves the method sensitivity to spectral changes and
      tolerance for baseline inclusion. Furthermore, a generalized formula is presented
      to unify further development of approaches to quantify spectral difference. 

PMID- 25051255
TI  - Bimetallic alloy nanocrystals encapsulated in ZIF-8 for synergistic catalysis of
      ethylene oxidative degradation.
AB  - Highly dispersed PtPd alloy nanocrystals (NCs) were firstly successfully
      encapsulated in microporous zeolitic imidazolate framework ZIF-8 (PtPd@ZIF-8)
      with tunable compositions by a "bottle around ship" approach. The PtPd@ZIF-8
      catalyst showed excellent synergistic photocatalytic activity in the
      transformation of the adsorbed ethylene into CO2 and H2O at room temperature. 

PMID- 25051256
TI  - Protective effects and mechanisms of total alkaloids of Rubus alceaefolius Poir
      on non-alcoholic fatty liver disease in rats.
AB  - The plant Rubus alceaefolius Poir is used as a hepatic protectant in Traditional
      Chinese Medicine. The aim of the present study was to confirm the protective
      effect of the total alkaloids of Rubus alceaefolius Poir (TARAP) on the liver and
      to evaluate the potential molecular mechanisms associated with adipocytokines
      underlying non-alcoholic fatty liver disease (NAFLD) in rats. To generate the
      NAFLD model, Sprague-Dawley rats were administered a high-fat diet and following
      12 weeks of model construction, rats were orally treated with a positive control
      drug and different doses of TARAP daily for 28 days. The rats were then
      sacrificed and the livers were collected to evaluate the liver index (LI) and
      observe histological changes by hematoxylin and eosin (H&E) staining. The
      secretion levels of alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) in serum were examined by ELISA. Finally, the expression levels of leptin
      (LEP), resistin and adiponectin (APN) in liver tissues were determined by
      immunohistochemistry (IHC). The results demonstrated that, in the group treated
      with methionine and choline bitartrate tablets and in the groups treated with
      different doses of TARAP, there was a significant reduction in the LI (P<0.05 or
      P<0.01), a downregulation of the secretion levels of ALT and AST, reduced levels
      of LEP and resistin and an increased expression of APN in the liver of NAFLD rats
      compared with the model group. Furthermore, the effect of TARAP treatment of
      NAFLD rats was dose dependent. In conclusion, TARAP is a potential agent for
      downregulating LEP and resistin and upregulating APN expression in rats with
      NAFLD. Furthermore, TARAP may be a potential candidate for improving treatment
      responses in patients with NAFLD.

PMID- 25051257
TI  - Nanoparticle conversion chemistry: Kirkendall effect, galvanic exchange, and
      anion exchange.
AB  - Conversion chemistry is a rapidly maturing field, where chemical conversion of
      template nanoparticles (NPs) into new compositions is often accompanied by
      morphological changes, such as void formation. The principles and examples of
      three major classes of conversion chemical reactions are reviewed: the Kirkendall
      effect for metal NPs, galvanic exchange, and anion exchange, each of which can
      result in void formation in NPs. These reactions can be used to obtain complex
      structures that may not be attainable by other methods. During each kind of
      conversion chemical reaction, NPs undergo distinct chemical and morphological
      changes, and insights into the mechanisms of these reactions will allow for
      improved fine control and prediction of the structures of intermediates and
      products. Conversion of metal NPs into oxides, phosphides, sulphides, and
      selenides often occurs through the Kirkendall effect, where outward diffusion of
      metal atoms from the core is faster than inward diffusion of reactive species,
      resulting in void formation. In galvanic exchange reactions, metal NPs react with
      noble metal salts, where a redox reaction favours reduction and deposition of the
      noble metal (alloying) and oxidation and dissolution of the template metal
      (dealloying). In anion exchange reactions, addition of certain kinds of anions to
      solutions containing metal compound NPs drives anion exchange, which often
      results in significant morphological changes due to the large size of anions
      compared to cations. Conversion chemistry thus allows for the formation of NPs
      with complex compositions and structures, for which numerous applications are
      anticipated arising from their novel catalytic, electronic, optical, magnetic,
      and electrochemical properties. 

PMID- 25051262
TI  - What's new in the management of traumatic brain injury on neuro ICU?
AB  - PURPOSE OF REVIEW: In recent years, we have begun to better understand how to
      monitor the injured brain, look for less common complications and importantly,
      reduce unnecessary and potentially harmful intervention. However, the lack of
      consensus regarding triggers for intervention, best neuromonitoring techniques
      and standardization of therapeutic approach is in need of more careful study.
      This review covers the most recent evidence within this exciting and dynamic
      field. RECENT FINDINGS: The role of intracranial pressure monitoring has been
      challenged; however, it still remains a cornerstone in the management of the
      severely brain-injured patient and should be used to compliment other techniques,
      such as clinical examination and serial imaging.The use of multimodal monitoring
      continues to be refined and it may be possible to use them to guide novel brain
      resuscitation techniques, such as the use of exogenous lactate supplementation in
      the future. SUMMARY: Neurocritical care management of traumatic brain injury
      continues to evolve. However, it is important not to use a 'one-treatment-fits
      all' approach, and perhaps look to use targeted therapies to individualize
      treatment.

PMID- 25051259
TI  - Lead-induced iron overload and attenuated effects of ferroportin 1 overexpression
      in PC12 cells.
AB  - Lead (Pb) neurotoxicity has received renewed interest with the growing evidence
      that Pb contributes to Alzheimer's disease (AD). However, the mechanism is not
      clear. In our previous study of long-term Pb exposure in vivo, a brain iron (Fe)
      overload induced by Pb was observed in elderly rats. It is well known that brain
      Fe overload is the mechanism of AD. Therefore, we have reason to believe that Pb
      induced Fe overload and caused neurodegenerative disease. However, the mechanism
      or route of Pb-induced Fe overload is unknown. In the current study, the effect
      of Pb exposure on Fe homeostasis in PC12 cells was determined at different Pb
      exposure concentrations and periods with differing Fe exposure, and the role of
      ferroportin 1 (FP1), the sole iron efflux protein, in Pb-induced Fe metabolic
      disorders was further investigated. The results showed a Pb-induced cellular
      increase in Fe accompanying a decrease in the expression of FP1 in a
      concentration- and time-dependent manner in Pb-exposed PC12 cells. Furthermore,
      FP1 overexpression could attenuate Fe accumulation in Pb-exposed PC12 cells.
      These results indicated that FP1 might be a novel target to prevent cellular Fe
      accumulation induced by Pb exposure and subsequent neurotoxic consequences.

PMID- 25051260
TI  - Regional anesthesia in patients with pre-existing neurologic disease.
AB  - PURPOSE OF REVIEW: Regional anesthesia is controversial in patients with pre
      existing neurologic disease. This study reviews the published evidence regarding
      the utilization and outcomes of regional anesthetics in this population. RECENT
      FINDINGS: Although publications are sparse, neuraxial and peripheral regional
      techniques have been successfully described in patients with spinal cord injury,
      multiple sclerosis, Guillain-Barre disease, neurofibromatosis, diseases of the
      neuromuscular junction, and Charcot-Marie Tooth disease without neurologic
      complications. Ultrasound guidance may aid in reduction in local anesthetic dose,
      anatomical evaluation and avoidance of needle trauma. SUMMARY: Regional
      anesthesia can be safely utilized in patients with pre-existing neurological
      disease and may have benefits over general anesthesia; however, a conservative
      approach is warranted. In addition, further publications regarding regional
      techniques in this population are needed.

PMID- 25051261
TI  - Spinal anesthesia revisited: toxicity of new and old drugs and compounds.
AB  - PURPOSE OF REVIEW: Neural toxicity of substances injected into the intrathecal
      space has been a matter of debate since the introduction of spinal anesthesia in
      clinical practice. In recent years, new local anesthetics and adjuvants have been
      proposed for intrathecal use, and new techniques such as the use of ultrasound
      have been propagated. The present review summarizes recent clinical and
      experimental data on the neurotoxic effects of drugs and substances used for or
      in conjunction with spinal anesthesia. RECENT FINDINGS: Chloroprocaine has been
      demonstrated to be associated with a lower risk of transient neurologic symptoms
      compared with lidocaine. However, despite extensive research, the issue of
      chloroprocaine or bisulfite neurotoxicity has not yet been resolved.Recent
      experimental data have identified a smaller neurotoxic potential for ropivacaine
      compared to levobupivacaine, procaine and bupivacaine. The addition of
      epinephrine has not been shown to increase lidocaine neurotoxicity. In-vivo
      experimental data suggest that lidocaine and bupivacaine neurotoxicity is not
      enhanced in diabetic patients.Furthermore, intrathecal introduction of aqueous
      ultrasound gel has been demonstrated to cause a distinct neuroinflammatory
      reaction. Finally, a large cohort study did not find the use of chlorhexidine
      gluconate for skin disinfection before neuraxial block to be associated with the
      risk of adhesive arachnoiditis. SUMMARY: Clinical data suggest a high safety
      profile for intrathecal drugs and substances used for or in conjunction with
      spinal anesthesia. Recent experimental models for toxicity have provided further
      insight into the mechanisms and demonstrated possible, albeit clinically small
      differences in the relative neurotoxic potential of intrathecal drugs. This may
      contribute to a further increase in the safe use of spinal anesthesia in the
      clinical setting.

PMID- 25051263
TI  - Red blood cell transfusion in neurosurgical patients.
AB  - PURPOSE OF REVIEW: Anemia is common in neurosurgical patients, and is associated
      with secondary brain injury. Although recent studies in critically ill patients
      have shifted practice toward more restrictive red blood cell (RBC) transfusion
      strategies, the evidence for restrictive versus liberal transfusion strategies in
      neurosurgical patients has been controversial. In this article, we review recent
      studies that highlight issues in RBC transfusion in neurosurgical patients.
      RECENT FINDINGS: Recent observational, retrospective studies in patients with
      traumatic brain injury, subarachnoid hemorrhage, and intracranial hemorrhage have
      demonstrated that prolonged anemia and RBC transfusions were associated with
      worsened outcomes. Anemia in patients with ischemic stroke was associated with
      increased ICU length of stay and longer mechanical ventilation requirements, but
      mortality and functional outcomes did not improve with RBC transfusion. In
      elective craniotomy, perioperative anemia was associated with increased hospital
      length of stay but no difference in 30-day morbidity or mortality. SUMMARY: There
      is a lack of definitive evidence to guide RBC transfusion practices in
      neurosurgical patients. Large randomized control trials are needed to better
      assess when and how aggressively to transfuse RBCs in neurosurgical patients.

PMID- 25051264
TI  - Chronic pain after surgery in children.
AB  - PURPOSE OF REVIEW: To present the recent literature on chronic postsurgical pain
      in children. RECENT FINDINGS: Chronic postsurgical pain is an important problem
      in children, however, with a lower prevalence than in adults. SUMMARY: The
      literature on the topic is sparse. Prospective studies, including clinical
      examination, quantitative sensory testing, and long-term follow-up, are needed to
      increase our knowledge about the prevalence, risk factors, and underlying
      mechanisms.

PMID- 25051265
TI  - Craniotomy in sitting position: anesthesiology management.
AB  - PURPOSE OF REVIEW: Sitting position to surgically approach posterior fossa
      disorder continues to be the first choice for some neurosurgical teams. We
      underwent a literature research for recent published studies involving
      neurosurgical patients operated on in this position. Preoperative evaluation,
      anesthetic technique, intraoperative monitoring, detection and treatment of
      venous or arterial air embolism episodes, and all the reported complications were
      recorded. RECENT FINDINGS: A modified semisitting (lounging) position aiming to
      create a positive pressure in the transverse and sigmoid sinuses, with lower head
      and higher legs positioned above the top of the head, decreases the incidence and
      severity of venous air embolism. Hyperventilation, compromising cerebral blood
      flow, has to be avoided during a sitting position. Precordial Doppler or
      transesophageal echocardiography monitoring improves the detection of small
      venous air embolism enabling its early treatment and diminishing its
      consequences. Patients with known patent foramen ovale can be operated on in a
      sitting position, under strict protocol, with few reported clinical venous air
      embolism and no paradoxical air embolism. SUMMARY: Sitting position for
      neurosurgical procedures may be a well tolerated approach for the patient if
      neurosurgeons and neuroanesthesiologists undergo a strict team protocol,
      including all necessary monitoring and meticulously followed.

PMID- 25051266
TI  - Torilis japonica extract, a new potential EMT suppressor agent by regulation of
      EGFR signaling pathways.
AB  - Abnormal metastasis of carcinoma is associated with the loss of epithelial
      features and the acquisition of a mesenchymal phenotype. The stimulation of cells
      with epidermal growth factor (EGF) resulted in morphological changes and induced
      epithelial-mesenchymal transition (EMT). EGF stimulation resulted in increased
      mobility along with upregulated actin polarization related proteins, E-cadherin
      regulators and the mesenchymal markers. Treatment with Torilis japonica extract
      (TJE) along with stimulation by EGF prevented changes in cell morphology,
      mobility, expression of actin polarization proteins and EMT markers. Using
      specific inhibitors and siEGFR, it was demonstrated that TJE suppressed EMT
      through EGFR inactivation and regulation of its downstream signaling pathways. We
      suggest that TJE is a new potential reagent for EGFR-targeted therapy and anti
      abnormal metastasis in MCF-7 breast cancer. 

PMID- 25051267
TI  - Schlemm's canal is a unique vessel with a combination of blood vascular and
      lymphatic phenotypes that forms by a novel developmental process.
AB  - Schlemm's canal (SC) plays central roles in ocular physiology. These roles depend
      on the molecular phenotypes of SC endothelial cells (SECs). Both the specific
      phenotype of SECs and development of SC remain poorly defined. To allow a modern
      and extensive analysis of SC and its origins, we developed a new whole-mount
      procedure to visualize its development in the context of surrounding tissues. We
      then applied genetic lineage tracing, specific-fluorescent reporter genes,
      immunofluorescence, high-resolution confocal microscopy, and three-dimensional
      (3D) rendering to study SC. Using these techniques, we show that SECs have a
      unique phenotype that is a blend of both blood and lymphatic endothelial cell
      phenotypes. By analyzing whole mounts of postnatal mouse eyes progressively to
      adulthood, we show that SC develops from blood vessels through a newly discovered
      process that we name "canalogenesis." Functional inhibition of KDR (VEGFR2), a
      critical receptor in initiating angiogenesis, shows that this receptor is
      required during canalogenesis. Unlike angiogenesis and similar to stages of
      vasculogenesis, during canalogenesis tip cells divide and form branched chains
      prior to vessel formation. Differing from both angiogenesis and vasculogenesis,
      during canalogenesis SECs express Prox1, a master regulator of lymphangiogenesis
      and lymphatic phenotypes. Thus, SC development resembles a blend of vascular
      developmental programs. These advances define SC as a unique vessel with a
      combination of blood vascular and lymphatic phenotypes. They are important for
      dissecting its functions that are essential for ocular health and normal vision. 

PMID- 25051271
TI  - Adsorption of carboxylic modified latex particles at liquid interfaces studied by
      the gel trapping technique.
AB  - We have studied how carboxylic modified latex (CML) microparticles adsorb at
      liquid surfaces and the preferred type of emulsion they can stabilise depending
      on the particle size and the surface density of carboxylic groups. We measured
      the particle contact angle by using the gel trapping technique (GTT) for CML
      particles adsorbed at air-water and oil-water interfaces. Using this method we
      obtained scanning electron microscopy (SEM) micrographs of polydimethylsiloxane
      (PDMS) replicas of the liquid interface with the particles, where the PDMS
      replicates the non-polar phase and measured the particle contact angle. We
      discovered that the particle wettability correlates well with the surface density
      of the carboxylic groups but is not very sensitive to the presence of electrolyte
      in the aqueous phase and the value of the particle zeta potential. We
      demonstrated that CML microparticles with a high surface density of COOH groups
      stabilise oil-in-water (O/W) emulsions while those with the lowest coverage of
      COOH groups favour the formation of water-in-oil (W/O) emulsions. We found that
      this corresponds to a change of the CML particle contact angle from lower than 90
      degrees  to higher than 90 degrees  upon decrease of the surface density of COOH
      groups. The findings confirm that the surface density of polar groups has a much
      bigger effect on the particle wettability and the preferred emulsion than the
      particle surface charge and zeta potential. Our results on the type of stabilised
      Pickering emulsion agree with other experimental studies with different particle
      materials. We propose an alternative explanation for the link between the
      particle contact angle and the type of stabilised Pickering emulsion. 

PMID- 25051268
TI  - Arousal vs. relaxation: a comparison of the neurophysiological and cognitive
      correlates of Vajrayana and Theravada meditative practices.
AB  - Based on evidence of parasympathetic activation, early studies defined meditation
      as a relaxation response. Later research attempted to categorize meditation as
      either involving focused or distributed attentional systems. Neither of these
      hypotheses received strong empirical support, and most of the studies
      investigated Theravada style meditative practices. In this study, we compared
      neurophysiological (EEG, EKG) and cognitive correlates of meditative practices
      that are thought to utilize either focused or distributed attention, from both
      Theravada and Vajrayana traditions. The results of Study 1 show that both focused
      (Shamatha) and distributed (Vipassana) attention meditations of the Theravada
      tradition produced enhanced parasympathetic activation indicative of a relaxation
      response. In contrast, both focused (Deity) and distributed (Rig-pa) meditations
      of the Vajrayana tradition produced sympathetic activation, indicative of
      arousal. Additionally, the results of Study 2 demonstrated an immediate dramatic
      increase in performance on cognitive tasks following only Vajrayana styles of
      meditation, indicating enhanced phasic alertness due to arousal. Furthermore, our
      EEG results showed qualitatively different patterns of activation between
      Theravada and Vajrayana meditations, albeit highly similar activity between
      meditations within the same tradition. In conclusion, consistent with Tibetan
      scriptures that described Shamatha and Vipassana techniques as those that calm
      and relax the mind, and Vajrayana techniques as those that require 'an awake
      quality' of the mind, we show that Theravada and Vajrayana meditations are based
      on different neurophysiological mechanisms, which give rise to either a
      relaxation or arousal response. Hence, it may be more appropriate to categorize
      meditations in terms of relaxation vs. arousal, whereas classification methods
      that rely on the focused vs. distributed attention dichotomy may need to be
      reexamined. 

PMID- 25051272
TI  - Spatial biases in mental arithmetic.

PMID- 25051269
TI  - Human plasma lipid modulation in schistosomiasis mansoni depends on
      apolipoprotein E polymorphism.
AB  - BACKGROUND: Schistosomiasis mansoni is a parasitic liver disease, which causes
      several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein
      E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma
      lipid levels in patients with hepatosplenic schistosomiasis.
      METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were used for APOE genotyping and
      to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides.
      Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and
      32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C
      was increased (10% higher; P = 0.0136). Frequency of the common alleles,
      epsilon2, epsilon3 and epsilon4, was similar (P = 0.3568) between controls (n =
      108) and patients (n = 84), implying that APOE genotype did not affect
      susceptibility to the advanced stage of schistosomiasis. Nevertheless, while
      patient TC and LDL-C levels were significantly reduced for each allele (except TC
      in epsilon2 patients), changes in HDL-C and triglycerides were noted only for the
      less common epsilon2 and epsilon4 alleles. The most striking finding, however,
      was that accepted regulation of plasma lipid levels by APOE genotype was
      disrupted by schistosomiasis. Thus, while epsilon2 controls had higher TC and LDL
      C than epsilon3 carriers, these parameters were lower in epsilon2 versus epsilon3
      patients. Similarly, the inverse relationship of TG levels in controls
      (epsilon2>epsilon3>epsilon4) was absent in patients (epsilon2 or
      epsilon4>epsilon3), and the increase in HDL-C of epsilon2 or epsilon4 patients
      compared to epsilon3 patients was not seen in the control groups.
      CONCLUSION/SIGNIFICANCE: We confirm that human schistosomiasis causes
      dyslipidemia and report for the first time that certain changes in plasma lipid
      and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also
      concluded that S. mansoni disrupts the expected regulation of plasma lipids by
      the different ApoE isoforms. This finding suggests ways to identify new metabolic
      pathways affected by schistosomiasis and also potential molecular targets to
      treat associated morbidities.

PMID- 25051273
TI  - Spatial associations in numerical cognition--from single digits to arithmetic.
AB  - The literature on spatial associations during number processing is dominated by
      the SNARC (spatial-numerical association of response codes) effect. We describe
      spatial biases found for single digits and pairs of numbers, first in the
      "original" speeded parity task and then extending the scope to encompass
      different tasks, a range of measures, and various populations. Then we review
      theoretical accounts before surveying the emerging evidence for similar spatial
      associations during mental arithmetic. We conclude that the mental number line
      hypothesis and an embodied approach are useful frameworks for further studies. 

PMID- 25051274
TI  - Doing arithmetic by hand: hand movements during exact arithmetic reveal
      systematic, dynamic spatial processing.
AB  - Mathematics requires precise inferences about abstract objects inaccessible to
      perception. How is this possible? One proposal is that mathematical reasoning,
      while concerned with entirely abstract objects, nevertheless relies on neural
      resources specialized for interacting with the world-in other words, mathematics
      may be grounded in spatial or sensorimotor systems. Mental arithmetic, for
      instance, could involve shifts in spatial attention along a mental "number-line",
      the product of cultural artefacts and practices that systematically spatialize
      number and arithmetic. Here, we investigate this hypothesized spatial processing
      during exact, symbolic arithmetic (e.g., 4 + 3 = 7). Participants added and
      subtracted single-digit numbers and selected the exact solution from responses in
      the top corners of a computer monitor. While they made their selections using a
      computer mouse, we recorded the movement of their hand as indexed by the
      streaming x, y coordinates of the computer mouse cursor. As predicted, hand
      movements during addition and subtraction were systematically deflected toward
      the right and the left, respectively, as if calculation involved simultaneously
      simulating motion along a left-to-right mental number-line. This spatial
      arithmetical bias, moreover, was distinct from-but correlated with-individuals'
      spatial-numerical biases (i.e., spatial-numerical association of response codes,
      SNARC, effect). These results are the first evidence that exact, symbolic
      arithmetic prompts systematic spatial processing associated with mental
      calculation. We discuss the possibility that mathematical calculation relies, in
      part, on an integrated system of spatial processes. 

PMID- 25051275
TI  - Two case reports of severe pediatric hyperosmolar hyperglycemia and diabetic
      ketoacidosis accompanied with rhabdomyolysis and acute renal failure.
AB  - OBJECTIVE: This report describes two adolescent males in China who suffered from
      type 2 diabetes mellitus (T2DM) and hyperglycemic hyperosmolar syndrome (HHS)
      complicated by rhabdomyolysis (RM). After sufficient fluid administration, both
      patients recovered. DESIGN: Case report. RESULTS: These two obese patients
      suffered from T2DM, DKA and HHS. Because of insufficient fluid administration,
      these patients became aggravated and suffered from RM. After aggressive fluid
      resuscitation and insulin injection, the conditions of the two patients improved.
      Insulin administration was ceased after approximately 1 month of subcutaneous
      injections. The two patients attained good glucose control with diet management.
      CONCLUSIONS: HHS is one of the most severe complications of T2DM. RM is a sign
      that the condition of a patient with HHS may worsen. Although management
      strategies are undefined, effective fluid infusion was shown to be helpful. Thus,
      the early signs of HHS and RM should be recognized so as to avoid severe
      complications.

PMID- 25051277
TI  - Wiring prior to firing: the evolutionary rise of electrical and chemical modes of
      synaptic transmission.
AB  - Paracrine signaling and coupling via intercellular conduits are widely utilized
      for cell-cell interactions from primitive eukaryotes to advanced metazoa. Here,
      we review the functional and molecular data suggestive of a phylogenic continuum
      between these primeval forms of communication with the chemical and electrical
      synaptic transmission of neurons. We discuss selective evidence for the essential
      role played by the shift of function in early cellular morphologies and
      protosynaptic scaffolds, with their co-optation for new functionality, which
      ultimately lead to the rise of the chemical synapse. It is proposed that, rather
      than representing a transitional element, mixed electrochemical synapses
      exemplify an exaptive effect. The nonadaptive model of the synaptic origin
      described herein supports the pluralistic hypothesis of evolutionary change.

PMID- 25051278
TI  - Phytonutrients as therapeutic agents.
AB  - Nutrients present in various foods plays an important role in maintaining the
      normal functions of the human body. The major nutrients present in foods include
      carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are
      some bioactive food components known as "phytonutrients" that play an important
      role in human health. They have tremendous impact on the health care system and
      may provide medical health benefits including the prevention and/or treatment of
      disease and various physiological disorders. Phytonutrients play a positive role
      by maintaining and modulating immune function to prevent specific diseases. Being
      natural products, they hold a great promise in clinical therapy as they possess
      no side effects that are usually associated with chemotherapy or radiotherapy.
      They are also comparatively cheap and thus significantly reduce health care cost.
      Phytonutrients are the plant nutrients with specific biological activities that
      support human health. Some of the important bioactive phytonutrients include
      polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids,
      limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, omega-3
      fatty acids, and probiotics. They play specific pharmacological effects in human
      health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic,
      anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic,
      neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic,
      protection from UVB-induced carcinogenesis, immuno-modulator, and carminative.
      This mini-review attempts to summarize the major important types of
      phytonutrients and their role in promoting human health and as therapeutic agents
      along with the current market trend and commercialization.

PMID- 25051276
TI  - Optogenetic studies of nicotinic contributions to cholinergic signaling in the
      central nervous system.
AB  - Molecular manipulations and targeted pharmacological studies provide a compelling
      picture of which nicotinic receptor subtypes are where in the central nervous
      system (CNS) and what happens if one activates or deletes them. However,
      understanding the physiological contribution of nicotinic receptors to endogenous
      acetylcholine (ACh) signaling in the CNS has proven a more difficult problem to
      solve. In this review, we provide a synopsis of the literature on the use of
      optogenetic approaches to control the excitability of cholinergic neurons and to
      examine the role of CNS nicotinic ACh receptors (nAChRs). As is often the case,
      this relatively new technology has answered some questions and raised others.
      Overall, we believe that optogenetic manipulation of cholinergic excitability in
      combination with some rigorous pharmacology will ultimately advance our
      understanding of the many functions of nAChRs in the brain.

PMID- 25051279
TI  - Predictors of 7- and 30-day mortality in pediatric intensive care unit patients
      with cancer and hematologic malignancy infected with Gram-negative bacteria.
AB  - BACKGROUND: Infection with Gram-negative bacteria is associated with increased
      morbidity and mortality. The aim of this study was to evaluate the predictors of
      7- and 30-day mortality in pediatric patients in an intensive care unit with
      cancer and/or hematologic diseases and Gram-negative bacteria infection. METHODS:
      Data were collected relating to all episodes of Gram-negative bacteria infection
      that occurred in a pediatric intensive care unit between January 2009 and
      December 2012, and these cases were divided into two groups: those who were
      deceased seven and 30 days after the date of a positive culture and those who
      survived the same time frames. Variables of interest included age, gender,
      presence of solid tumor or hematologic disease, cancer status, central venous
      catheter use, previous Pseudomonas aeruginosa infection, infection by multidrug
      resistant-Gram-negative bacteria, colonization by multidrug resistant-Gram
      negative bacteria, neutropenia in the preceding seven days, neutropenia duration
      >=3 days, healthcare-associated infection, length of stay before intensive care
      unit admission, length of intensive care unit stay >3 days, appropriate empirical
      antimicrobial treatment, definitive inadequate antimicrobial treatment, time to
      initiate adequate antibiotic therapy, appropriate antibiotic duration <=3 days,
      and shock. In addition, use of antimicrobial agents, corticosteroids,
      chemotherapy, or radiation therapy in the previous 30 days was noted. RESULTS:
      Multivariate logistic regression analysis resulted in significant relationship
      between shock and both 7-day mortality (odds ratio 12.397; 95% confidence
      interval 1.291-119.016; p=0.029) and 30-day mortality (odds ratio 6.174; 95%
      confidence interval 1.760-21.664; p=0.004), between antibiotic duration <=3 days
      and 7-day mortality (odds ratio 21.328; 95% confidence interval 2.834-160.536;
      p=0.003), and between colonization by multidrug resistant-Gram-negative bacteria
      and 30-day mortality (odds ratio 12.002; 95% confidence interval 1.578-91.286;
      p=0.016). CONCLUSIONS: Shock was a predictor of 7- and 30-day mortality, and
      colonization by multidrug resistant-Gram-negative bacteria was an important risk
      factor for 30-day mortality.

PMID- 25051280
TI  - Extra-pulmonary Pneumocystis jiroveci infection: a case report.
AB  - In physical examination abdominal tenderness, gate disturbance and penile
      herpetic lesions were detected. Decreased disc height at T11-T12 level was
      detected in chest X-ray. Abdominal sonography and CT scan revealed hypo dense
      lesions in Lt left Lobe of liver and multiple hypo dense splenic and pancreatic
      lesions, ascitis, Lt left sided pleural effusion, thickening of jejuneal mucosa
      and edema of bowel wall. Vertebral body lesion and paravertebral abscess, bony
      calvarial involvement and adjacent extra axial brain lesion were observed in
      imaging were other findings. RNA analysis for HIV was positive. Vertebral lesion
      biopsy and aspiration of splenic lesion were performed and pathology revealed
      Pneumocystis jirovecii suggestive of extra pulmonary Pneumocystis carinii
      infection. 

PMID- 25051281
TI  - Erythropoietin promotes the protective properties of transplanted endothelial
      progenitor cells against acute lung injury via PI3K/Akt pathway.
AB  - INTRODUCTION: Accumulating evidences have indicted the participation and
      repairing effects of endothelial progenitor cells (EPCs) on acute lung injury
      (ALI). Researchers have also revealed that erythropoietin (EPO) may exert
      multiple effects on EPCs including proliferative and adhesive properties. The
      present study was designed to investigate whether EPO can promote the healing
      efficiency of transplanted EPCs against ALI and the potential mechanism. METHODS:
      Endothelial progenitor cells were derived from bone marrow mononuclear cells of
      BALB/c mice. In our in vitro studies, we tested the proproliferative and
      antiapoptotic effects of EPO on cultured EPCs. In our in vivo studies, we induced
      BALB/c mice ALI model by intratracheal instillation of lipopolysaccharide and
      treated with/without intravenous injection of enhanced green fluorescent protein
      EPCs harvested from enhanced green fluorescent protein-BALB/c mice. Mice that
      received EPC transplantation either underwent EPO administration or not. The
      effects of EPO and EPC treatment on promoting pulmonary endothelial repair,
      decreasing pulmonary capillary permeability, alleviating pulmonary inflammation,
      improving gas exchange, and promoting pulmonary vessel angiogenesis were tested.
      The potential mechanisms that mediate EPO functions on EPC were also
      investigated. RESULTS: Our studies revealed a significant antiapoptotic property
      of EPO on cultured EPCs as well as its promotion on EPC proliferation. We also
      found the severity of ALI was reduced by EPC therapy, and the protective effects
      of EPCs were highly enhanced when combined with EPO administration. However, all
      these stimulating effects of EPO on EPCs were consisted with the expression of
      phospho-Akt and were abrogated by PI3K inhibitors. CONCLUSIONS: Transplanted EPCs
      directly incorporated into the injured pulmonary vessels and maintain the
      integrity of pulmonary endothelium. Erythropoietin improved the survival and
      proliferation of transplanted EPCs and recruited them to the injured sites to
      exert their repairing functions. PI3K/Akt pathway mediated EPO's functions on
      EPCs. The combination of EPO and EPC treatment may be a promising cell-based
      therapy for ALI patients.

PMID- 25051282
TI  - Abrupt reflow enhances cytokine-induced proinflammatory activation of endothelial
      cells during simulated shock and resuscitation.
AB  - Circulatory shock and resuscitation are associated with systemic hemodynamic
      changes, which may contribute to the development of MODS (multiple organ
      dysfunction syndrome). In this study, we used an in vitro flow system to simulate
      the consecutive changes in blood flow as occurring during hemorrhagic shock and
      resuscitation in vivo. We examined the kinetic responses of different endothelial
      genes in human umbilical vein endothelial cells preconditioned to 20 dyne/cm
      unidirectional laminar shear stress for 48 h to flow cessation and abrupt reflow,
      respectively, as well as the effect of flow cessation and reflow on tumor
      necrosis factor-alpha (TNF-alpha)-induced endothelial proinflammatory activation.
      Endothelial CD31 and VE-cadherin were not affected by the changes in flow in the
      absence or presence of TNF-alpha. The messenger RNA levels of proinflammatory
      molecules E-selectin, VCAM-1 (vascular cell adhesion molecule 1), and IL-8
      (interleukin 8) were significantly induced by flow cessation respectively acute
      reflow, whereas ICAM-1 (intercellular adhesion molecule 1) was downregulated on
      flow cessation and induced by subsequent acute reflow. Flow cessation also
      affected the Ang/Tie2 (Angiopoietin/Tie2 receptor tyrosine kinase) system by
      downregulating Tie2 and inducing its endothelial ligand Ang2, an effect that was
      further extended on acute reflow. Furthermore, the induction of proinflammatory
      adhesion molecules by TNF-alpha under flow cessation was significantly enhanced
      on subsequent acute reflow. This study demonstrated that flow alterations per se
      during shock and resuscitation contribute to endothelial activation and that
      these alterations interact with proinflammatory factors coexisting in vivo such
      as TNF-alpha. The abrupt reflow-related enhancement of cytokine-induced
      endothelial proinflammatory activation supports the concept that sudden regain of
      flow during resuscitation has an aggravating effect on endothelial activation,
      which may play a significant role in vascular dysfunction and consequent organ
      injury. This study implies that the improvement of resuscitation strategies and
      the pharmacological interference with proinflammatory signaling cascades at the
      right time of resuscitation of shock patients may be beneficial to regain and/or
      maintain organ function in patients after circulatory shock. 

PMID- 25051283
TI  - Endotoxemic myocardial dysfunction: subendocardial collagen deposition related to
      coronary driving pressure.
AB  - Sepsis impairs the autoregulation of myocardial microcirculatory blood flow, but
      whether this impairment is correlated with myocardial remodeling is unknown. This
      study investigated the role of coronary driving pressure (CDP) as a determinant
      of microcirculatory blood flow and myocardial fibrosis in endotoxemia and sepsis.
      The study is composed of two parts: a prospective experimental study and an
      observational clinical study. The experimental study was performed on male Wistar
      rats weighing 300 to 320 g. Endotoxemia was induced in rats by lipopolysaccharide
      (LPS) injection (10 mg.kg intraperitoneally). Hemodynamic evaluation was
      performed 1.5 to 24 h after LPS injection by measuring the mean arterial
      pressure, CDP, left ventricular end-diastolic pressure, dP/dtmax, and dP/dtmin.
      Microspheres were also infused into the left ventricle to measure myocardial
      blood flow, and myocardial tissue was histologically assessed to analyze collagen
      deposition. The CDP, mean arterial pressure, and myocardial blood flow were
      reduced by 55%, 30%, and 70%, respectively, in rats 1.5 h after LPS injection
      compared with phosphate buffer saline injection (P < 0.05). The CDP was
      significantly correlated with subendocardial blood flow (r = 0.73) and fibrosis
      (r = 0.8). Left ventricular function was significantly impaired in the LPS
      treated rats, as demonstrated by dP/dtmax (6,155 +/- 455 vs. 3,746 +/- 406
      mmHg.s, baseline vs. LPS; P < 0.05) and dP/dtmin (-5,858 +/- 236 vs. -3,516 +/-
      436 mmHg.s, baseline vs. LPS; P < 0.05). The clinical study was performed on 28
      patients with septic shock analyzed for CDP. The CDP data and histological slices
      were collected from septic patients. In addition, the clinical data demonstrated
      fibrosis and 45% CDP reduction in nonsurvivors compared with survivors. In
      conclusion, the left ventricular subendocardial blood flow was positively
      correlated with CDP, and higher CDP was negatively correlated with myocardial
      collagen deposition. Thus, early reductions in myocardial blood flow and CDP
      facilitate late myocardial fibrosis in rats and likely in humans. 

PMID- 25051285
TI  - Protection against intestinal injury from hemorrhagic shock by direct peritoneal
      resuscitation with pyruvate in rats.
AB  - OBJECTIVE: We explored the effects of direct peritoneal resuscitation with
      pyruvate-peritoneal dialysis solution (PDS) following intravenous resuscitation
      (VR) on intestinal ischemia-reperfusion injury in rats with hemorrhagic shock
      (HS). METHODS: Fifty rats were randomly assigned equally to five groups. In group
      sham, a surgical operation was performed on rats without shock or resuscitation.
      In group VR, rats were subjected only to VR. In groups NS, LA, and PY, direct
      peritoneal resuscitation was performed with normal saline (NS), lactate-based PDS
      (Lac-PDS), and pyruvate-based PDS (Pyr-PDS), respectively, after VR. Mean
      arterial pressure was monitored in the right common carotid artery. Two hours
      after resuscitation, the lactate level in arterial blood and the wet weight/dry
      weight ratio of the intestine were determined. The intestinal mucosal damage
      index was estimated, and ultrastructural changes in the intestinal mucosa were
      observed. Malondialdehyde, myeloperoxidase, nitric oxide, and tumor necrosis
      factor alpha levels were also measured. RESULTS: Two hours after HS and
      resuscitation, the increase in arterial blood lactate and intestinal wet
      weight/dry weight ratio declined significantly in rats from Groups LA and PY
      compared with groups VR and NS, whereas group PY was more advantageous in the
      changes of these parameters. The intestinal mucosal damage index and
      ultrastructural changes were also improved in groups LA and PY when compared with
      groups VR and NS. Protection was more apparent with Pyr-PDS than Lac-PDS.
      Hemorrhagic shock resulted in a significant increase in malondialdehyde levels
      and myeloperoxidase activity and was accompanied by overexpression of tumor
      necrosis factor alpha and a reduction in nitric oxide levels. These changes were
      significantly attenuated by Lac-PDS and Pyr-PDS at 2 h after resuscitation, and
      Pyr-PDS showed more effective protection for the intestine than Lac-PDS.
      CONCLUSIONS: Direct peritoneal resuscitation with Lac-PDS and Pyr-PDS after VR
      alleviated intestinal injury from HS in rats, and Pyr-PDS was superior to Lac-PDS
      in its protective effect. Mechanisms of action might include the elimination of
      free oxygen radicals, reduction of neutrophil infiltration, inhibition of the
      inflammatory response, and regulation of intestinal mucosal blood flow and
      barrier function.

PMID- 25051284
TI  - Persistent lymphopenia after diagnosis of sepsis predicts mortality.
AB  - OBJECTIVE: The objective of this study was to determine whether persistent
      lymphopenia on the fourth day following the diagnosis of sepsis predicts
      mortality. METHODS: This was a single-center, retrospective cohort study of 335
      adult patients with bacteremia and sepsis admitted to a large university
      affiliated tertiary care hospital between January 1, 2010, and July 31, 2012. All
      complete blood cell count profiles during the first 4 days following the
      diagnosis of sepsis were recorded. The primary outcome was 28-day mortality.
      Secondary outcomes included development of secondary infections, 1-year
      mortality, and hospital and intensive care unit lengths of stay. RESULTS: Seventy
      six patients (22.7%) died within 28 days. Lymphopenia was present in 28-day
      survivors (median, 0.7 * 10 cells/MUL; interquartile range [IQR], 0.4-1.1 * 10
      cells/MUL) and nonsurvivors (median, 0.6 * 10 cells/MUL; IQR, 0.4-1.1 * 10
      cells/MUL) at the onset of sepsis and was not significantly different between the
      groups (P = 0.35). By day 4, the median absolute lymphocyte count was
      significantly higher in survivors compared with nonsurvivors (1.1 * 10 cells/MUL
      [IQR, 0.7-1.5 * 10 cells/MUL] vs. 0.7 * 10 cells/MUL [IQR, 0.5-1.0 * 10
      cells/MUL]; P < 0.0001). Using logistic regression to account for potentially
      confounding factors (including age, Acute Physiology and Chronic Health
      Evaluation II score, comorbidities, surgical procedure during the study period,
      and time until appropriate antibiotic administration), day 4 absolute lymphocyte
      count was found to be independently associated with 28-day survival (adjusted
      odds ratio, 0.68 [95% confidence interval, 0.51-0.91]) and 1-year survival
      (adjusted odds ratio, 0.74 [95% confidence interval, 0.59-0.93]). Severe
      persistent lymphopenia (defined as an absolute lymphocyte count of 0.6 * 10
      cells/MUL or less on the fourth day after sepsis diagnosis) was associated with
      increased development of secondary infections (P = 0.04). CONCLUSIONS: Persistent
      lymphopenia on the fourth day following the diagnosis of sepsis predicts early
      and late mortality and may serve as a biomarker for sepsis-induced
      immunosuppression.

PMID- 25051286
TI  - Caffeine and menopausal symptoms: what is the association?
AB  - OBJECTIVE: We assessed the association between caffeine intake and menopausal
      symptom bother, particularly vasomotor symptoms. METHODS: A cross-sectional
      survey was conducted using the Menopause Health Questionnaire, which is a
      comprehensive survey of menopause-related health information. Questionnaires were
      completed by 2,507 consecutive women who presented with menopausal concerns at
      the Women's Health Clinic at Mayo Clinic (Rochester, MN) between July 25, 2005
      and July 25, 2011. Data from 1,806 women who met all inclusion criteria were
      analyzed. Menopausal symptom ratings were compared between women who used
      caffeine and women who did not use caffeine using two-sample t test and analysis
      of covariance, with smoking and menopause status included as covariates. In all
      cases, two-tailed P < 0.05 was considered statistically significant. RESULTS:
      Caffeine use was positively associated with mean (SD) vasomotor symptom scores
      (2.30 [0.91] vs 2.15 [0.94], P = 0.011). This finding remained significant after
      adjustment for menopause status and cigarette smoking (P = 0.027). CONCLUSIONS:
      Caffeine use is associated with greater vasomotor symptom bother in
      postmenopausal women.

PMID- 25051287
TI  - Epistasis between polymorphisms in ACVR2B and ADAMTS19 is associated with
      premature ovarian failure.
AB  - OBJECTIVE: This study investigated whether epistasis between single nucleotide
      polymorphisms (SNPs) within ACVR2B (activin A receptor, type IIB) and ADAMTS19
      (ADAM metallopeptidase with thrombospondin type 1 motif, 19) genes is associated
      with premature ovarian failure (POF). METHODS: One hundred twenty women with POF
      and 152 controls were recruited for stage I, and 1,641 additional female controls
      participated in stage II. GoldenGate assay with VeraCode technology was used for
      genotyping ACVR2B and ADAMTS19 SNPs in stage I. In stage II, we obtained genotype
      data for SNPs using Affymetrix Genome-Wide Human SNP array 5.0 and imputed data
      using IMPUTE program from the Korean Genome Epidemiology Study. RESULTS: In stage
      I, five combinations showed significant synergistic interactions after Bonferroni
      correction. One SNP (rs1468077 within 5' flanking region) and two intronic SNPs
      (rs2268753 and rs2268757) in ACVR2B and three intronic SNPs within ADAMTS19
      (rs13158524, rs1476083, and rs1972624) were involved in synergistic interactions
      in a recessive manner. In stage II and combined analyses, we could not find any
      significant interactions between the SNPs. However, diplotypes within ACVR2B and
      ADAMTS19 that consist of risk genotypes or alleles in the results of significant
      synergistic interactions between SNPs showed significant interactions after
      Bonferroni correction. Thirteen and nine significant synergistic interactions
      were found in a dominant model in stage II and combined analyses, respectively
      (strongest association in combined analysis: odds ratio, 5.93; 95% CI, 2.47
      14.20; P = 6.65 * 10(-5)). CONCLUSIONS: Epistasis between polymorphisms within
      ACVR2B and ADAMTS19 is significantly associated with susceptibility to POF.

PMID- 25051288
TI  - Miniature hygrometric hot flush recorder as an objective indicator of hot
      flushes: a validation study.
AB  - OBJECTIVE: Hot flushes are a very common symptom of menopause for which many
      women seek medical help. Accurate assessment of clinical severity and of the
      impact of treatment is limited by a lack of methods for objective hot flush
      recording. The aim of the current study is to test the diagnostic value of a
      miniature hygrometric hot flush recorder (HFR). METHODS: The HFR was tested in 50
      women with severe postmenopausal hot flushes. Results were compared with
      recordings in 27 asymptomatic postmenopausal women, 12 premenopausal women, and
      12 age-matched healthy men. The number of HFR events was compared with the number
      of diary-reported hot flushes. RESULTS: Healthy young women and men had a mean
      (SEM) of 17.3 (1.3) HFR events/day. Asymptomatic postmenopausal women had 13.6
      (1.4) HFR events/day, whereas symptomatic postmenopausal women had 21.0 (1.0) HFR
      events/day (P < 0.001). The number of HFR events in symptomatic women was
      significantly higher than the number of diary-reported hot flushes (mean [SEM],
      13.8 [0.6] hot flushes/d) (P < 0.001). HFR sensitivity to diary-reported hot
      flushes was 55.1%, with 61.4% specificity. CONCLUSIONS: The miniature hygrometric
      HFR has limited sensitivity and specificity. It detects sweating in general but
      does not differentiate between natural sweating and hot flush-related sweating.
      However, it may become useful as a tool for improving the data quality of diary
      reported hot flushes.

PMID- 25051289
TI  - Use of hormone therapy in Swedish women aged 80 years or older.
AB  - OBJECTIVE: Menopausal symptoms such as hot flashes and night sweats may persist
      for 10 to 20 years or even longer. Information about the extent to which older
      women use hormone therapy is limited. The aim of this study was to determine the
      use of hormone therapy in Swedish women aged 80 years or older. METHODS: The
      study is based on national register data on dispensed drug prescriptions (ie,
      prescribed therapy that has been provided to individuals by pharmacies) for
      hormone therapy and local low-dose estrogens. RESULTS: Of 310,923 Swedish women
      who were aged at least 80 years, 609 (0.2%) were new users of hormone therapy. A
      total of 2,361 women (0.8%) were current users of hormone therapy. The median
      duration of hormone therapy use in new users was 257 days (25th to 75th
      percentiles, 611-120 d). About one in six women aged 80 years or older had used
      local vaginal estrogen therapy for at least four 3-month periods. The drugs were
      mainly prescribed by gynecologists and general practitioners. CONCLUSIONS: Our
      results show that a number of women aged 80 years or older still use hormone
      therapy and that most women who started a new treatment period had only one or
      two dispensations despite the median duration of treatment being more than half a
      year. Because at least some of the women aged 80 years or older who used hormone
      therapy probably did so owing to persistent climacteric symptoms, vasomotor
      symptoms and hormone therapy are still relevant issues that need to be discussed
      when counseling women around and after age 80.

PMID- 25051290
TI  - Recent advances help understand and improve the safety of menopausal therapies.
AB  - OBJECTIVE: Hormone therapy (HT) remains a mainstay of treatment of vasomotor
      symptoms, which are among the most common and most bothersome of menopausal
      symptoms. This review provides updates on HT and reviews newer menopausal
      therapies, focusing on recent safety data. METHODS: An interpretative review of
      recent medical literature was conducted using computerized databases. RESULTS:
      The latest analyses from the Women's Health Initiative and other trials suggest
      that there is a window shortly after the onset of menopause in which HT provides
      optimal benefit with minimal risk. Risks of breast cancer, coronary heart
      disease, and probable dementia increase when a progestin is included in the HT
      regimen, which is necessary in nonhysterectomized women to counter the
      proliferative effects of estrogens on the endometrium. Attempts to further
      optimize the risk-benefit profile of menopausal therapies have led to the
      introduction of newer selective estrogen receptor modulators (bazedoxifene for
      osteoporosis, ospemifene for dyspareunia), tissue-selective estrogen complexes
      (conjugated estrogens/bazedoxifene for vasomotor symptoms and osteoporosis), and
      non-HT (low-dose paroxetine for vasomotor symptoms). CONCLUSIONS: Recent studies
      suggest that HT has a neutral or even beneficial effect on coronary heart disease
      and cognition when used in the early postmenopausal years. The risk-to-benefit
      ratio of estrogen therapy in hysterectomized women is more favorable than that of
      estrogen-progestin regimens in nonhysterectomized women. Conjugated
      estrogens/bazedoxifene now provides a progestin-free option for managing
      vasomotor symptoms in postmenopausal women with an intact uterus. Low-dose
      paroxetine may be an alternative for some women when hormonal treatments are
      contraindicated.

PMID- 25051291
TI  - For vasomotor symptoms, timing-and duration-may be everything.

PMID- 25051292
TI  - Association of breast arterial calcification with stroke and angiographically
      proven coronary artery disease: a meta-analysis.
AB  - OBJECTIVE: We conducted a meta-analysis of the current literature to deduce the
      strength of association between breast arterial calcification (BAC) and coronary
      artery disease (CAD) and/or stroke. METHODS: PubMed, Google Scholar,
      ClinicalTrials.gov, and Ovid were searched for English-language literature up to
      August 2013 using the terms "breast arterial calcification," "breast vascular
      calcification," "coronary artery disease," "coronary heart disease,"
      "cardiovascular disease," "abnormal coronary angiography," and "stroke." A hand
      search of the reference lists of key articles was performed to supplement the
      literature search. Our literature search revealed 75 articles for further
      abstract review. Limiting our search to articles that quantitatively assessed the
      correlation between BAC and stroke or angiographically proven CAD, we reviewed 35
      full manuscripts. Of these articles, 14 were included in the final analysis.
      RESULTS: We analyzed 10 cross-sectional studies (n = 3,952) with CAD as the
      primary outcome (diagnosed by coronary angiography). The odds ratio (95% CI) for
      CAD in those with BAC versus those without BAC is 3.86 (3.25-4.59) (P < 0.0001).
      For stroke, six cross-sectional studies were analyzed (n = 18,888). The odds
      ratio (95% CI) for stroke in those with BAC versus those without BAC is 1.54
      (1.25-1.90) (P < 0.0001). CONCLUSIONS: These results suggest that BAC is
      significantly associated with both CAD and stroke. Although more prospective
      studies are warranted to clarify whether BAC is truly a predictor of the future
      development of CAD and stroke, the concept that BAC is a benign finding is
      waning.

PMID- 25051293
TI  - Indium tin oxide-free tandem polymer solar cells on opaque substrates with top
      illumination.
AB  - Top-illuminated, indium tin oxide (ITO)-free, tandem polymer solar cells are
      fabricated on opaque substrates in an inverted device configuration. In the
      tandem cell, a wide band gap subcell, consisting of poly[N-9'-heptadecanyl-2,7
      carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT)
      blended with [70]PCBM is combined with a small band gap subcell consisting of a
      mixture of poly[{2,5-bis(2-hexyldecyl)-2,3,5,6-tetrahydro-3,6-dioxopyrrolo[3,4
      c]pyrrole-1,4-diyl}-alt-{[2,2'-(1,4-phenylene)bisthiophene]-5,5'-diyl}] (PDPPTPT)
      and [60]PCBM. Compared to the more common bottom-illuminated inverted tandem
      polymer solar cells on transparent ITO substrates, the front and back cells must
      be reversed when using opaque substrates and a transparent and conductive top
      contact must be employed to enable top illumination. A high conductive poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) layer in combination
      with Ag lines surrounding the active area as current collection electrode is used
      for this purpose. The tandem polymer solar cell on an opaque glass/metal
      substrate yields a power conversion efficiency of 6.1% when the thicknesses of
      the photoactive layers are balanced for optimum performance. This is similar to
      the equivalent inverted tandem device fabricated on a transparent glass/ITO
      substrate. 

PMID- 25051294
TI  - Changes in salivary estradiol predict changes in women's preferences for vocal
      masculinity.
AB  - Although many studies have reported that women's preferences for masculine
      physical characteristics in men change systematically during the menstrual cycle,
      the hormonal mechanisms underpinning these changes are currently poorly
      understood. Previous studies investigating the relationships between measured
      hormone levels and women's masculinity preferences tested only judgments of men's
      facial attractiveness. Results of these studies suggested that preferences for
      masculine characteristics in men's faces were related to either women's estradiol
      or testosterone levels. To investigate the hormonal correlates of within-woman
      variation in masculinity preferences further, here we measured 62 women's
      salivary estradiol, progesterone, and testosterone levels and their preferences
      for masculine characteristics in men's voices in five weekly test sessions.
      Multilevel modeling of these data showed that changes in salivary estradiol were
      the best predictor of changes in women's preferences for vocal masculinity. These
      results complement other recent research implicating estradiol in women's mate
      preferences, attention to courtship signals, sexual motivation, and sexual
      strategies, and are the first to link women's voice preferences directly to
      measured hormone levels. 

PMID- 25051295
TI  - The beginning of an end point: peak AST in liver transplantation.

PMID- 25051296
TI  - Heat-shock response transcriptional program enables high-yield and high-quality
      recombinant protein production in Escherichia coli.
AB  - The biosynthesis of soluble, properly folded recombinant proteins in large
      quantities from Escherichia coli is desirable for academic research and
      industrial protein production. The basal E. coli protein homeostasis
      (proteostasis) network capacity is often insufficient to efficiently fold
      overexpressed proteins. Herein we demonstrate that a transcriptionally
      reprogrammed E. coli proteostasis network is generally superior for producing
      soluble, folded, and functional recombinant proteins. Reprogramming is
      accomplished by overexpressing a negative feedback deficient heat-shock response
      transcription factor before and during overexpression of the protein-of-interest.
      The advantage of transcriptional reprogramming versus simply overexpressing
      select proteostasis network components (e.g., chaperones and co-chaperones, which
      has been explored previously) is that a large number of proteostasis network
      components are upregulated at their evolved stoichiometry, thus maintaining the
      system capabilities of the proteostasis network that are currently incompletely
      understood. Transcriptional proteostasis network reprogramming mediated by stress
      responsive signaling in the absence of stress should also be useful for protein
      production in other cells. 

PMID- 25051297
TI  - Endogenous cortisol levels influence exposure therapy in spider phobia.
AB  - Previous research in patients with phobia showed that the administration of
      glucocorticoids reduces fear in phobic situations and enhances exposure therapy.
      Glucocorticoids underlie a daily cycle with a peak in the morning and low levels
      during the evening and night. The aim of the present study was to investigate
      whether exposure is more effective when conducted in the morning when endogenous
      cortisol levels are high. Sixty patients meeting DSM IV criteria for specific
      phobia (animal type) were randomly assigned to one-session exposure treatment
      either at 08.00 a.m. (high cortisol group) or at 06.00 p.m. (low cortisol group).
      Participants returned for a posttreatment assessment one week after therapy and a
      follow-up assessment three months after therapy. Both groups showed good outcome,
      but patients treated in the morning exhibited significantly less fear of spiders
      in the behavioral approach test (BAT) and a trend for lower scores on the Fear of
      Spiders Questionnaire (FSQ) than patients treated in the evening. This effect was
      present at posttreatment and follow-up. Our findings indicate that exposure
      therapy is more effective in the morning than in the evening. We suggest that
      this may be due to higher endogenous cortisol levels in the morning group that
      enhance extinction memory.

PMID- 25051298
TI  - Selective hydrogenation of butadiene over TiO2 supported copper, gold and gold
      copper catalysts prepared by deposition-precipitation.
AB  - Oxide supported copper and gold catalysts are active for the selective
      hydrogenation of polyunsaturated hydrocarbons but their low activity compared to
      palladium catalysts and the deactivation of copper catalysts limit their use.
      There are only a very limited number of studies concerned with the use of
      bimetallic Au-Cu catalysts for selective hydrogenation reactions and the aim of
      this work was to prepare TiO2-supported monometallic Au and Cu and bimetallic
      AuCu (Cu/Au atomic ratio of 1 and 3) catalysts and to evaluate their catalytic
      performance in the selective hydrogenation of butadiene. Small gold, copper and
      gold-copper nanoparticles (average particle size < 2 nm) were obtained on TiO2
      using the preparation method of deposition-precipitation with urea followed by
      reduction under H2 at 300  degrees C. Very small clusters were observed for
      Cu/TiO2 (~1 nm) which might result from O2 induced copper redispersion, as also
      supported by the XPS analyses. The alloying of copper with gold was found to
      inhibit its redispersion and also limits its reoxidation, as attested by XPS. The
      bimetallic character of the AuCu nanoparticles was confirmed by XPS and EDX
      HAADF. Cu/TiO2 was initially more active than Au/TiO2 in the selective
      hydrogenation of butadiene at 75  degrees C but it deactivated rapidly during the
      first hours of reaction whereas the gold catalyst was very stable up to 20 hours
      of reaction. The bimetallic AuCu/TiO2 catalysts displayed an activation period
      during the first hours of the reaction, which was very pronounced for the sample
      containing a higher Cu/Au atomic ratio. This initial gain in activity was
      tentatively assigned to copper segregation at the surface of the bimetallic
      nanoparticles, induced by the reactants. When the AuCu/TiO2 catalysts were pre
      exposed to air at 75  degrees C before butadiene hydrogenation, surface copper
      segregation occurred, leading to higher initial activity and the suppression of
      the activation period. Under the same conditions, Cu/TiO2 totally lost its
      activity, probably due to irreversible copper oxidation. 

PMID- 25051299
TI  - Influence of mutation type on prognostic and predictive values of TP53 status in
      primary breast cancer patients.
AB  - High rates of mutation in the TP53 tumor suppressor gene have been found in many
      human cancers, including breast tumors, making p53 one of the most studied
      proteins in oncology. However, the prognostic and predictive value of alterations
      in this gene remains ambiguous. To analyze the clinical value of somatic TP53
      mutations, we collected clinical and molecular data on 210 women with primary
      breast cancer. We found significant associations of p53 mutations with tumor
      grade, metastasis, molecular subtype, Her2 status and inverse correlations with
      estrogen and progesterone receptor status. Cox proportional hazard analysis
      confirmed a strong prognostic value of p53 mutation for overall survival rate and
      highlighted significant interactions with lymph node involvement and tumor size.
      In relation to treatment options, TP53 mutations were associated with poor
      response to anthracyclines and radiotherapy. Categorization of TP53 mutations
      according to their type and location revealed that patients with nonsense
      mutation have the poorest prognosis in comparison with wild-type cases and other
      types of mutations in this gene. Classification of TP53 mutations with respect to
      the degree of disturbance of protein structure showed association of disruptive
      mutations with poorer patients' outcome in contrast to wild-type and non
      disruptive mutations. In conclusion, the present study confirms p53 as a
      potential predictive and prognostic factor in oncology practice and highlights
      the growing evidence that distinct types of mutations have different clinical
      impacts. 

PMID- 25051300
TI  - Investigation of processes in black tea manufacture through model fermentation
      (oxidation) experiments.
AB  - Flavanol depleted whole fresh green tea leaf powder, as reported in the
      literature, was used as matrix for a systematic study of the endogenous oxidative
      enzymatic conversion of selected flavanol combinations to theaflavins and
      thearubigins. The activity of the two crucial enzymes polyphenol oxidase (PPO)
      and peroxidase (POD) was controlled individually through addition of H2O2 and/or
      O2. Using the endogenous peroxidase only it was shown that (-)-epicatechin alone
      did not react with POD. According to these results it is possible that theaflavin
      formation occurs via reaction of a flavanol quinone with a nonquinone flavanol.
      It was confirmed that only a dihydroxy-B-ring flavanol with a trihydroxy-B-ring
      flavanol gave a theaflavin upon enzymatic oxidation. Use of horseradish
      peroxidase in the presence of a flavanol depleted tea leaf matrix led to
      significantly higher kinetics on theaflavin 3-gallate degradation compared to the
      absence of leaf matrix, suggesting a catalytic effect of the leaf matrix not
      reported before. 

PMID- 25051302
TI  - Association of cardiometabolic risk profile with prehypertension accompany
      hyperhomocysteinaemia.
AB  - BACKGROUND: Study suggested that elevated homocysteine showed a multiplicative
      effect on cardiovascular diseases in hypertensive subjects. It was reported that
      elevated homocysteine level was independently associated with increased arterial
      stiffness in prehypertensives. It remains unclear whether prehypertensives
      combined with elevated homocysteine have adverse cardiovascular risk factors. We
      aimed to compare cardiometabolic risk profile between prehypertensives with
      hyperhomocysteinaemia and those without either condition. METHODS: Plasma total
      homocysteine and risk profile were determined among 874 Chinese non-hypertension
      individuals in Tianjin. They were subdivided into four groups: prehypertension
      with hyperhomocysteinaemia (>=10 MUmol/L), prehypertension with normal
      homocysteine (<10 MUmol/L), normotension with hyperhomocysteinaemia, normotension
      with normol homocysteine, respectively. RESULTS: In 874 participants, 22.5% of
      them were male, mean age was 56.8 years. In multiple comparisons, after
      adjustment for age, gender, smoking, alcohol, exercise, education
      prehypertensives had higher body mass index (BMI) and high sensitive C reactive
      protein (hs-CRP) than normotensives (p < 0.05, respectively); Only
      prehypertensive subjects with hyperhomocysteinaemia had higher triglyceride and
      serum uric acid compared to normotensive subjects, and lower HDL cholesterol than
      normotensives with normal homocysteine (p < 0.05, respectively). However, the
      significance of higher hs-CRP, uric acid and lower HDL cholesterol were abolished
      when further adjustment was made for BMI. CONCLUSION: The combination of
      prehypertension and hyperhomocusteinaemia increases the likelihood of having
      adverse cardiometabolic risk profile. Strict lipid management and weigh control
      may be needed in prehypertensives with elevated homocysteine.

PMID- 25051305
TI  - Use of a free ocean CO2 enrichment (FOCE) system to evaluate the effects of ocean
      acidification on the foraging behavior of a deep-sea urchin.
AB  - The influence of ocean acidification in deep-sea ecosystems is poorly understood
      but is expected to be large because of the presumed low tolerance of deep-sea
      taxa to environmental change. We used a newly developed deep-sea free ocean CO2
      enrichment (dp-FOCE) system to evaluate the potential consequences of future
      ocean acidification on the feeding behavior of a deep-sea echinoid, the sea
      urchin, Strongylocentrotus fragilis. The dp-FOCE system simulated future ocean
      acidification inside an experimental enclosure where observations of feeding
      behavior were performed. We measured the average movement (speed) of urchins as
      well as the time required (foraging time) for S. fragilis to approach its
      preferred food (giant kelp) in the dp-FOCE chamber (-0.46 pH units) and a control
      chamber (ambient pH). Measurements were performed during each of 4 trials (days 
      2, 2, 24, 27 after CO2 injection) during the month-long period when groups of
      urchins were continuously exposed to low pH or control conditions. Although
      urchin speed did not vary significantly in relation to pH or time exposed,
      foraging time was significantly longer for urchins in the low-pH treatment. This
      first deep-sea FOCE experiment demonstrated the utility of the FOCE system
      approach and suggests that the chemosensory behavior of a deep-sea urchin may be
      impaired by ocean acidification.

PMID- 25051304
TI  - Zinc bioaccumulation and ionoregulatory impacts in Fundulus heteroclitus exposed
      to sublethal waterborne zinc at different salinities.
AB  - Exposure of Fundulus heteroclitus to an environmentally relevant Zn concentration
      (500 MUg L-1) at different salinities (0, 3.5, 10.5, and 35 ppt) revealed the
      following effects: (i) plasma [Zn] doubled after exposure at 0 ppt, a response
      which was eliminated at 35 ppt. Tissue [Zn] also increased in gill, liver,
      intestine, and carcass at 0 ppt. (ii) Both branchial and intestinal Ca2+ ATPase
      activities decreased in response to Zn at 0 ppt and were elevated at 35 ppt.
      Plasma [Ca] decreased by 50% at 0 ppt and by 30% at 3.5 ppt and increased by 20%
      at 35 ppt. Gill [Ca] decreased by 35% at 0 ppt and increased by about 30% at all
      higher salinities. (iii) Branchial Na+,K+ ATPase activity decreased by 50% at 0
      ppt, increased by 30% and 90% at 10.5 and 35 ppt respectively. Intestinal Na+,K+
      ATPase activity was reduced by 30% at 0 ppt. (iv) Plasma [Na] decreased by 30% at
      0 ppt in Zn-exposed. Zn exposure also disturbed the homeostasis of tissue cations
      (Na+, K+, Ca++, Mg++) in a tissue-specific and salinity-dependent manner. (v)
      Drinking rate was not altered by Zn exposure. In toxicity tests, acute Zn
      lethality (96-h LC50) increased in a close to linear fashion from 9.8 mg L-1 at 0
      ppt to 75.0 mg L-1 at 35 ppt. We conclude that sublethal Zn exposure causes
      pathological changes in both Ca++ and Na+ homeostases, and that increasing
      salinity exerts protective effects against both sublethal and lethal Zn
      toxicities.

PMID- 25051306
TI  - Interfacing whispering gallery mode optical microresonator biosensors with the
      plant defense elicitor chitin.
AB  - The biomaterial class of chitooligosaccharides (chitin), commonly found in
      insects and fungi, is one of the most abundant on earth. Substantial evidence
      implicates chitin in mediating a diverse array of plant cellular signaling
      events, including the induction of plant defense mechanisms against invading
      pests. However, these recognition and mediation mechanisms, including the binding
      kinetics between chitin and their plant recognition receptors, are not fully
      understood. Therefore, the creation of a platform capable of both interfacing
      with chitin and plant cell receptors, and monitoring their interactions, would
      significantly advance our understanding of this plant defense elicitor. Recently,
      a label-free, highly sensitive biosensor platform, based on Whispering Gallery
      Mode optical microresonators, has been developed to study such biomolecular
      interactions. Here, we demonstrate how this unique platform can be interfaced
      with chitin using simple carbohydrate chemistry. The surface chemistry is
      demonstrated using X-ray photoelectron spectroscopy, fluorescence microscopy,
      optical profilometry, ellipsometry, and contact angle measurements. The resulting
      surface is uniform, with an average surface roughness of 1.25nm, and is active
      toward chitin recognition elements. Optical loss measurements using standard
      quantitative cavity analysis techniques demonstrate that the bioconjugated
      platforms maintain the high performance (Q>10(6)) required to track binding
      interactions in this system. The platform is able to detect lectin, which binds
      COs, at 10MUg/mL concentration. This biosensor platform's unique capabilities for
      label-free, high sensitivity biodetection, when properly interfaced with the
      biomaterials of interest, could provide the basis for a robust analytical
      technique to probe the binding dynamics of chitin-plant cell receptors. 

PMID- 25051307
TI  - Erythrocyte membranes from slaughterhouse blood as potential drug vehicles:
      Isolation by gradual hypotonic hemolysis and biochemical and morphological
      characterization.
AB  - The present study was aimed at investigating the effect of isolation process
      gradual hypotonic hemolysis on chosen parameters of the erythrocyte membranes
      (ghosts) originating from bovine and porcine slaughterhouse blood. The estimation
      of the gradual hypotonic hemolysis as a drug loading procedure for the
      erythrocyte ghosts was performed as well. Based on the results derived from
      analysis of the osmotic properties of the erythrocytes, the gradual hemolysis was
      performed with high volume of erythrocytes and 35mM hypotonic sodium
      phosphate/NaCl, enabling >90% of hemolysis for both types of erythrocytes.
      Detailed insight into ghosts' morphology by field emission-scanning electron
      microscopy revealed a distortion from erythrocyte shape and an altered surface
      texture with increased bilayer curvature for both samples. Compared to
      erythrocytes, an average diameter of ghosts from both type of erythrocytes
      decreased for only about 10%. The reported unidispersity of the isolated ghosts
      is of great importance for their potential application as vehicles of active
      compounds. Gradual hemolysis did not lead to substantial loss of cholesterol and
      membrane/cytoskeleton proteins. This result indicated the ghosts' possibility to
      mimic the chemical and structural anisotropic environment of in vivo cell
      membranes, which is of significance for drug diffusion and partition
      coefficients. Induced shift of phosphatidylserine to external surface of the
      ghosts demonstrated their potential application as vehicles for targeted drug
      delivery to cells of reticuloendothelial system. Ultra high-performance liquid
      chromatography and Fourier transform infrared spectroscopy revealed the presence
      of a drug model - dexamethasone-sodium phosphate, and its interaction with
      structural components in both types of erythrocyte ghosts. 

PMID- 25051308
TI  - A nearly unavoidable mechanism for collider bias with index-event studies.
AB  - Factors suspected of causing certain chronic diseases and death are often
      associated with lower mortality among those with disease. For end-stage renal
      disease, examples include high cholesterol and homocysteine. Here, we consider
      obesity, thought to cause both end-stage renal disease and premature mortality,
      but which is associated with lower mortality among end-stage renal disease
      patients. Such seeming paradoxes could reflect collider (index event) bias due to
      selection of a diseased population for study. However, previous descriptions are
      incomplete, as they posit an uncontrolled factor causing both end-stage renal
      disease (the index event) and death. Here, we explicitly note that death can
      precede end-stage renal disease onset. The target population is obese persons
      with end-stage renal disease, effects of interest are seemingly controlled direct
      effects, the usual estimator is a conditional risk ratio, and remaining at risk
      until the onset of end-stage renal disease is a collider. Collider bias is then
      expected if any mortality risk factor is uncontrolled, even if no factor also
      affects end-stage renal disease. The bias is similar to, but differs from, that
      associated with competing risks. Because control of every mortality risk factor
      is implausible, bias of the standard estimator is practically unavoidable. Better
      awareness of these issues by clinicians and researchers is needed if
      observational research is to usefully guide care of this vulnerable patient
      population. 

PMID- 25051309
TI  - Indoor air pollution and neural tube defects: effect modification by maternal
      genes.
AB  - BACKGROUND: Gene-environment interactions have been implicated in the development
      of neural tube defects (NTDs). METHODS: We conducted a case-control study to
      investigate (1) the association of aryl hydrocarbon receptor (AHR) genetic
      variants and phase I metabolic enzymes with the risk of NTDs and (2) the
      interaction of these variants with maternal exposure to indoor air pollution from
      smoking and coal combustion or with placental polycyclic aromatic hydrocarbons
      (PAHs). Blood samples were collected from 534 mothers of fetuses or newborns with
      NTDs and 534 control mothers who had healthy term newborns and were assayed for
      12 polymorphisms in the AHR and cytochrome P450 (CYP) genes. Information on
      maternal exposure was collected, and placental levels of PAHs were analyzed.
      RESULTS: Maternal exposure to indoor air pollution was associated with an
      increased NTD risk. However, no increased NTD risk was observed for individual
      genetic variants. For mothers with the CYP1B1 rs2855658 GG variant, exposure to
      indoor air pollution led to a dose-response relationship for NTD risk, with odds
      ratios (ORs) of 3.0 (95% confidence interval = 1.6-5.7) and 8.1 (3.8-17) for
      medium and high levels of exposure, respectively. For mothers with GA or AA
      genotypes, this trend was less apparent. Placental PAHs were associated with an
      increased risk of NTDs, with an OR of 16 (3.3-75) for high levels compared with
      low levels of exposure among mothers with the GG genotype; there was no
      association for mothers with GA or AA genotypes. CONCLUSIONS: The CYP1B1 variant
      modifies the effect of indoor air pollution on NTD risk.

PMID- 25051310
TI  - Attributing effects to interactions.
AB  - A framework is presented that allows an investigator to estimate the portion of
      the effect of one exposure that is attributable to an interaction with a second
      exposure. We show that when the 2 exposures are statistically independent in
      distribution, the total effect of one exposure can be decomposed into a
      conditional effect of that exposure when the second is absent and also a
      component due to interaction. The decomposition applies on difference or ratio
      scales. We discuss how the components can be estimated using standard regression
      models, and how these components can be used to evaluate the proportion of the
      total effect of the primary exposure attributable to the interaction with the
      second exposure. In the setting in which one of the exposures affects the other,
      so that the 2 are no longer statistically independent in distribution,
      alternative decompositions are discussed. The various decompositions are
      illustrated with an example in genetic epidemiology. If it is not possible to
      intervene on the primary exposure of interest, the methods described in this
      article can help investigators to identify other variables that, if intervened
      upon, would eliminate the largest proportion of the effect of the primary
      exposure. 

PMID- 25051311
TI  - Physician's preference-based instrumental variable analysis: is it valid and
      useful in a moderate-sized study?
AB  - BACKGROUND: Instrumental variable methods can potentially circumvent the
      unmeasured confounding inherent in observational data analyses. METHODS: We
      investigated the validity and usefulness of physician's preference instrumental
      variable analysis in the setting of a moderate-sized clinical study. Using
      routine care data from 476 elective cardiac surgery patients, we assessed the
      effect of preoperative corticosteroids on mechanical ventilation time and
      duration of intensive care and hospital stay, occurrence of infections, atrial
      fibrillation, heart failure, and delirium. RESULTS: Although results of the
      physician's preference-based instrumental variable analysis corresponded in
      direction to results of a recent large randomized trial of the same therapy, the
      instrumental variable estimates showed much larger effects with very wide
      confidence intervals. CONCLUSION: The lesser statistical precision limits the
      usefulness of instrumental variable analysis in a study that might be of
      sufficient size for conventional analyses, even if a strong and plausible
      instrument is available.

PMID- 25051313
TI  - A conversation with Dimitrios Trichopoulos.

PMID- 25051314
TI  - Nanoscale insight into C-C coupling on cobalt nanoparticles.
AB  - The Ullmann coupling of bromobenzene to biphenyl on Co nanoparticles proceeds
      below room temperature via an intermediate in which phenyl groups are bound
      directly to metallic Co. A similar surface-bound benzyl intermediate is observed
      for coupling of benzylbromide to bibenzyl on Co. 

PMID- 25051312
TI  - In utero exposure to toxic air pollutants and risk of childhood autism.
AB  - BACKGROUND: Genetic and environmental factors are believed to contribute to the
      development of autism, but relatively few studies have considered potential
      environmental risks. Here, we examine risks for autism in children related to in
      utero exposure to monitored ambient air toxics from urban emissions. METHODS:
      Among the cohort of children born in Los Angeles County, California, 1995-2006,
      those whose mothers resided during pregnancy in a 5-km buffer around air toxics
      monitoring stations were included (n = 148,722). To identify autism cases in this
      cohort, birth records were linked to records of children diagnosed with primary
      autistic disorder at the California Department of Developmental Services between
      1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy
      for 24 air toxics selected based on suspected or known neurotoxicity or
      neurodevelopmental toxicity. Factor analysis helped us identify the correlational
      structure among air toxics, and we estimated odds ratios (ORs) for autism from
      logistic regression analyses. RESULTS: Autism risks were increased per
      interquartile range increase in average concentrations during pregnancy of
      several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR
      = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26
      1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40
      [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age,
      race/ethnicity, nativity, education, insurance type, parity, child sex, and birth
      year. CONCLUSIONS: Risks for autism in children may increase following in utero
      exposure to ambient air toxics from urban traffic and industry emissions, as
      measured by community-based air-monitoring stations.

PMID- 25051315
TI  - Effects of the polyphenol content on the anti-diabetic activity of Cinnamomum
      zeylanicum extracts.
AB  - Cinnamomum zeylanicum is a popular kitchen spice widely investigated for insulin
      potentiating effects. Though a group of water soluble polyphenols belonging to
      the oligomeric procyanidins has been identified as the bioactive principle, the
      lack of systematic information on the effect of the polyphenol content on safety
      and anti-diabetic efficacy remains as a major limitation for the development of
      optimized and standardized cinnamon extracts for functional use. In the present
      paper, water soluble extracts of Cinnamomum zeylanicum containing 45 and 75%
      gallic acid equivalents (GAE) of polyphenol content were prepared by a novel
      process and characterized by tandem mass spectrometry. The polyphenol enhanced
      extracts were shown to be safe and offered better antioxidant potential,
      hypoglycemic effect, hypolipidimic effect, and significant decrease in other
      biochemical parameters as compared to the standard aqueous extract containing 15%
      GAE, when administered to streptozotocin-induced diabetic rats at 200 mg per kg
      b.w. for 30 days. The efficacy of polyphenol extracts in lowering blood glucose
      levels and ameliorating oxidative stress was further demonstrated in humans by
      administrating 'procynZ-45' containing 45% GAE polyphenols at a relatively low
      dosage of (125 mg * 2) per day for 30 days to 15 volunteers who had elevated
      fasting blood glucose levels; but not involved in any medication. 

PMID- 25051316
TI  - Synthesis of oligomers of beta-l-arabinofuranosides of (4R)-4-hydroxy-l-proline
      relevant to the mugwort pollen allergen, Art v 1.
AB  - An efficient, convergent solution phase synthesis of monomer, dimer, trimer and
      tetramer of the beta-l-arabinofuranosylated hydroxyproline (beta-l-Araf-Hyp)
      glycocluster is described. This motif constitutes the carbohydrate-specific
      epitope of Art v 1, the major allergen of mugwort pollen. While a single
      monomeric unit was proposed at the outset, poor yields for the seemingly trivial
      steps of end-capping to replace protecting groups with N-terminal acetamides and
      C-terminal methyl amides led to the introduction of N-terminal, central and C
      terminal beta-l-Araf-Hyp building blocks. Dimer 2 was obtained in 60% yield by
      coupling of two monomers, followed by hydrogenolysis of benzyl ether protecting
      groups. Trimer 3 was obtained in 35% yield via a [2 + 1] coupling and tetramer 4
      in 15% yield via a [2 + 2] fragment condensation. Circular dichroism spectra show
      that monomer 1 displays no organized structure, whereas compounds 2-4 show a
      strong negative band at 200 nm and a weak positive band at ~220 mn, as is
      characteristic of the polyproline II helix. 

PMID- 25051317
TI  - MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer.
AB  - Gastric cancer (GC) is one of the most common malignancies worldwide. In
      particular, scirrhous type GC is highly metastatic and is characterized
      clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs)
      play crucial roles in cancer development and progression. We previously
      demonstrated by microarray analysis that microRNA-145 (miR-145) is one of the
      more highly expressed miRNAs in scirrhous type GC vs. non-scirrhous types of GC.
      In the present study, we investigated the role of miR-145 in scirrhous type GC.
      The expression levels of miR-145 assessed by quantitative RT-PCR were higher in
      scirrhous type GC tissue samples than in non-scirrhous type GC and corresponding
      normal tissues. GC patients with high miR-145 expression were at a more advanced
      tumor stage (P=0.0156) and had more scirrhous type histology (P=0.0054) than
      those with low miR-145 expression. Furthermore, miR-145 expression was
      significantly associated with poor prognosis in GC patients (P=0.0438). miR-145
      expression was localized in stromal fibroblasts of scirrhous type GC but not in
      cancer cells. miR-145 was induced by treatment by transforming growth factor
      beta, and it enhanced the expression of alpha-smooth muscle actin, a marker of
      myofibroblasts, in both normal gastric fibroblasts and cancer-associated
      fibroblasts. These data suggest that miR-145 may contribute to the progression of
      scirrhous type GC by regulating activation of peri-tumoral fibroblasts. 

PMID- 25051318
TI  - Ultrafast polarization response of an optically trapped single ferroelectric
      nanowire.
AB  - One-dimensional potassium niobate nanowires are of interest as building blocks in
      integrated piezoelectric devices, exhibiting large nonlinear optical and
      piezoelectric responses. Here we present femtosecond measurements of light
      induced polarization dynamics within an optically trapped ferroelectric nanowire,
      using the second-order nonlinear susceptibility as a real-time structural probe.
      Large amplitude, reversible modulations of the nonlinear susceptibility are
      observed within single nanowires at megahertz repetition rates, developing on few
      picosecond time-scales, associated with anomalous coupling of light into the
      nanowire. 

PMID- 25051319
TI  - Young adult females' perceptions of high-risk social media behaviors: a focus
      group approach.
AB  - This study describes young adult female college students' perceptions of risky
      social media behaviors. A sample of 14 young adult females, aged 18-22 years and
      residing in an urban university, participated in 1 of 3 focus groups held in
      campus housing. Data analysis yielded 4 themes surrounding young adults'
      engagement in risky behaviors associated with social media. Themes described the
      predominant culture, associated risk, and prevention. Important insights into
      young adult female college students' thoughts on risky social media behaviors can
      be used by advanced practice nurses to inform preventive education for young
      college women. 

PMID- 25051320
TI  - Assessing the need for a medical respite: perceptions of service providers and
      homeless persons.
AB  - For homeless persons, posthospitalization care is increasingly provided in formal
      medical respite programs, and their success is now reported in the literature.
      However, there is a dearth of literature on posthospitalization transitional care
      for homeless persons in the absence of a respite program. Through this formative
      study, we sought to understand the process of securing posthospitalization care
      in the absence of a formal homeless medical respite. Results demonstrated a de
      facto patchwork respite process that has emerged. We describe both human and
      monetary costs associated with patchwork respite and demonstrate opportunities
      for improvement in homeless health care transitions. 

PMID- 25051322
TI  - The role of the health care interpreter in a clinical setting--a narrative
      review.
AB  - OBJECTIVE: To examine published models of health care interpretation and
      associated roles, expectations, and outcomes. METHODS: A literature search was
      conducted using the key words interpreter/translator, communication, and role and
      their combinations in PubMed, CINAHL, PsycINFO, and PSYNDEXPlus. References
      mentioned in articles identified with these search terms were then checked by
      hand in corresponding publications and books. We excluded articles if they were
      dealing with concepts of interpretation, role definitions, etc., without
      presenting any empirical evidence to support their recommendations. Thirty-four
      of 1,121 references that investigated the role of professional interpreters in
      health care were found to meet inclusion criteria. RESULTS: Out of 34 articles,
      only 2 recommend strict adherence to the conduit model in which interpreters are
      faithfully and exclusively transmitting information; the interpreter's role is in
      32 studies defined in broader terms as the role of a cultural broker (n = 18), a
      manager or clarifier (n = 22), a patient advocate (n = 13), or a mediator (n =
      6). CONCLUSION: There are no commonly accepted understandings of the
      interpreters' role; empirical data are lacking. PRACTICE IMPLICATIONS: The
      interpreter's function must be explicitly clarified before a health care
      encounter is conducted. There should be an agreement of some basic rules.

PMID- 25051321
TI  - A profile of Mexican-born women who adhere to national cervical cancer screening
      recommendations.
AB  - The purpose of this study was to examine Mexican-born women's utilization and
      adherence to cervical cancer screening guidelines. Ninety-seven women in the
      southeastern United States participated. Data were collected in Spanish. The
      majority of women met adherence guidelines for the pap exam. Marital status,
      educational attainment, marianismo, blood pressure knowledge, fatalism, cultural
      cancer beliefs, trust in provider, and perceived provider communication abilities
      were not associated with utilization or adherence to screening guidelines. This
      study had higher than expected adherence to screening guidelines. Nearly all
      women received screenings through safety net services indicating the need to
      advocate for continued public health funding. 

PMID- 25051324
TI  - Mercury concentrations in amphipods and fish of the Saint Lawrence River (Canada)
      are unrelated to concentrations of legacy mercury in sediments.
AB  - Past industrial activity at Cornwall, Ontario, Canada has contaminated Lake Saint
      Francis, a fluvial lake on the Saint Lawrence River, with mercury (Hg). A spatial
      survey of Hg concentrations in sediments, amphipods, and yellow perch (Perca
      flavescens) in 2008 inferred current sources of Hg to the lake and spatial
      variations in risks to human consumers. Patterns of total and methyl Hg
      concentrations in sediment reflected upstream inputs, declining concentrations
      downstream, and highest concentrations at north shore sites near industrial
      sources; concentrations were lowest on the south shore because river currents
      limit north-south advective exchange. Surprisingly, concentrations of total or
      methyl Hg in sediments and pore water were unrelated to concentrations in
      amphipods and yellow perch. Concentrations in biota, and risks to consumers of
      fish, were highest at north shore sites near tributaries, and not at the most
      contaminated industrial sites. These results suggest that 'legacy' Hg in
      surficial sediments is not bioavailable to aquatic biota; tributaries and
      atmospheric deposition are possible sources of bioavailable Hg; and that sediment
      remediation would not resolve issues of Hg in fish. Fish consumption advisories
      for the entire lake based on single samples of fish could over- or under-protect
      consumers, depending on sampling location. To understand the actual risk to fish
      consumers for a large and complex lake system with multiple sources of Hg, more
      intensive sampling is needed to assess the spatial distribution of risk. 

PMID- 25051325
TI  - Modeling of pH-dependent adsorption and leaching of MCPA in profiles of Polish
      mineral soils.
AB  - This study aimed to determine the leaching potential of MCPA and the contribution
      of major soil components to its retention in 27 profiles of common Polish arable
      soils. Results of experiments and modeling of the pH-dependent adsorption
      indicated that the adsorption of the neutral and anionic forms of MCPA on soil
      organic matter are the predominant adsorption mechanisms, even in soil horizons
      with very low organic matter contents. The third most important mechanism was the
      adsorption of MCPA anions, most likely through the water bridging mechanism on
      sorption sites created by exchangeable Fe cations adsorbed in soil. It was found
      that in acidic soils with very low organic matter contents, the neutral form of
      MCPA was also adsorbed on the quartz and silica sorption sites of silt and sand.
      The value of r(2) was 78% when it was assumed that MCPA was adsorbed only on
      organic matter and 93% when all indicated mechanisms of adsorption on mineral
      soil components were included in the model fitted to data from all soil profiles.
      Simulations using FOCUS PELMO indicated that in two profiles, the 80th
      percentiles of the average yearly concentrations of MCPA in the leachate exceeded
      the European Union (EU) contamination limit of 0.1 MUgL(-1). It was shown that
      when an assumption was made in the model of pH-dependent adsorption that MCPA was
      adsorbed only on organic matter, the leaching potential of MCPA was overestimated
      in the examined soils. Much better predictions were obtained when adsorption on
      mineral soil components was also included in the model.

PMID- 25051326
TI  - Feeding strategies for groundwater enhanced biodenitrification in an alluvial
      aquifer: chemical, microbial and isotope assessment of a 1D flow-through
      experiment.
AB  - Nitrate-removal through enhanced in situ biodenitrification (EISB) is an existing
      alternative for the recovery of groundwater quality, and is often suggested for
      use in exploitation wells pumping at small flow-rates. Innovative approaches
      focus on wider-scale applications, coupling EISB with water-management practices
      and new monitoring tools. However, before this approach can be used, some water
      quality issues such as the accumulation of denitrification intermediates and/or
      of reduced compounds from other anaerobic processes must be addressed. With such
      a goal, a flow-through experiment using 100mg-nitrate/L groundwater was built to
      simulate an EISB for an alluvial aquifer. Heterotrophic denitrification was
      induced through the periodic addition of a C source (ethanol), with four
      different C addition strategies being evaluated to improve the quality of the
      denitrified water. Chemical, microbial and isotope analyses of the water were
      performed. Biodenitrification was successfully stimulated by the daily addition
      of ethanol, easily achieving drinking water standards for both nitrate and
      nitrite, and showing an expected linear trend for nitrogen and oxygen isotope
      fractionation, with a epsilonN/epsilonO value of 1.1. Nitrate reduction to
      ammonium was never detected. Water quality in terms of remaining C, microbial
      counts, and denitrification intermediates was found to vary with the experimental
      time, and some secondary microbial respiration processes, mainly manganese
      reduction, were suspected to occur. Carbon isotope composition from the remaining
      ethanol also changed, from an initial enrichment in (13)C-ethanol compared to the
      value of the injected ethanol (-30.60/00), to a later depletion, achieving
      delta(13)C values well below the initial isotope composition (to a minimum of 
      46.70/00). This depletion in the heavy C isotope follows the trend of an inverse
      fractionation. Overall, our results indicated that most undesired effects on
      water quality may be controlled through the optimization of the C/N ratio
      determined from the amounts of injected ethanol vs. the amount of nitrate in
      groundwater, with a smaller C/N ratio causing a lower level of undesired
      impurities. Furthermore, the authors suggest that the biofilm life-time has a
      direct effect on microbial population and hence affects biodenitrification
      performance, influencing the accumulation of nitrite over time.

PMID- 25051327
TI  - Effect of atmospheric mixing layer depth variations on urban air quality and
      daily mortality during Saharan dust outbreaks.
AB  - Several epidemiological studies have shown that the outbreaks of Saharan dust
      over southern European countries can cause negative health effects. The reasons
      for the increased toxicity of airborne particles during dust storms remain to be
      understood although the presence of biogenic factors carried by dust particles
      and the interaction between dust and man-made air pollution have been
      hypothesized as possible causes. Intriguingly, recent findings have also
      demonstrated that during Saharan dust outbreaks the local man-made particulates
      can have stronger effects on health than during days without outbreaks. We show
      that the thinning of the mixing layer (ML) during Saharan dust outbreaks,
      systematically described here for the first time, can trigger the observed higher
      toxicity of ambient local air. The mixing layer height (MLH) progressively
      reduced with increasing intensity of dust outbreaks thus causing a progressive
      accumulation of anthropogenic pollutants and favouring the formation of new fine
      particles or specific relevant species likely from condensation of accumulated
      gaseous precursors on dust particles surface. Overall, statistically significant
      associations of MLH with all-cause daily mortality were observed. Moreover, as
      the MLH reduced, the risk of mortality associated with the same concentration of
      particulate matter increased due to the observed pollutant accumulation. The
      association of MLH with daily mortality and the effect of ML thinning on particle
      toxicity exacerbated when Saharan dust outbreaks occurred suggesting a synergic
      effect of atmospheric pollutants on health which was amplified during dust
      outbreaks. Moreover, the results may reflect higher toxicity of primary particles
      which predominate on low MLH days. 

PMID- 25051328
TI  - Healthcare resource use and costs of privately insured patients who switch,
      discontinue, or persist on anti-muscarinic therapy for overactive bladder.
AB  - OBJECTIVES: To compare the healthcare costs of patients with overactive bladder
      (OAB) who switch vs persist on anti-muscarinic agents (AMs), describe resource
      use and costs among OAB patients who discontinue AMs, and assess factors
      associated with persisting vs switching or discontinuing. METHODS: OAB patients
      initiating an AM between January 1, 2007 and March 31, 2012 were identified from
      a claims database of US privately insured beneficiaries (n ~ 16 million) and
      required to have no AM claims in the 12 months before AM initiation (baseline
      period). Patients were classified as persisters, switchers, or discontinuers, and
      assigned a study index date based on their AM use in the 6 months following
      initiation. Baseline characteristics, resource use, and costs were compared
      between persisters and the other groups. Resource use and costs in the 1 month
      before and 6 months after the study index date (for switchers, the date of index
      AM switching; for persisters, a randomly assigned date to reflect the
      distribution of the time from AM initiation to switching among switchers) were
      also compared between persisters and switchers in unadjusted and adjusted
      analyses. Factors associated with persisting vs switching or discontinuing were
      assessed. RESULTS: After controlling for baseline characteristics and costs,
      persisters vs switchers had significantly lower all-cause and OAB-related costs
      in both the month before (all-cause $1222 vs $1759, OAB-related $142 vs $170) and
      6 months after the study index date (all-cause $7017 vs $8806, OAB-related $642
      vs $797). Factors associated with switching or discontinuing vs persisting
      included index AM, younger age, and history of UTI. CONCLUSION: A large
      proportion of OAB patients discontinue or switch AMs shortly after initiation,
      and switching is associated with higher costs.

PMID- 25051329
TI  - Microfluidic platforms for advanced risk assessments of nanomaterials.
AB  - In the past few years, promising efforts to utilize microfabrication-based
      technologies have laid the foundation for developing advanced, and importantly
      more physiologically-realistic, microfluidic methods for risk assessment of
      engineered nanomaterials (ENMs). In the present review, we discuss the wave of
      recent developments using microfluidic-based in vitro models and platforms for
      nanotoxicological assays, such as determination of cell viability, cellular dose,
      oxidative stress and nuclear damage. Here, we specifically highlight the tangible
      advantages of microfluidic devices in providing promising tools to tackle many of
      the current and ongoing challenges faced with traditional toxicology assays. Most
      importantly, microfluidic technology not only allows to recreate physiologically
      relevant in vitro models for nanotoxicity examinations, but also provides
      platforms that deliver an attractive strategy towards improved control over
      applied ENM doses. In a final step, we present examples of state-of-the-art
      microfluidic platforms for in vitro assessment of potential adverse ENM effects.

PMID- 25051330
TI  - Repeated intravenous injections in non-human primates demonstrate preclinical
      safety of an anti-inflammatory phosphorus-based dendrimer.
AB  - Dendrimers are nanosized hyperbranched polymers synthesized through an iterative
      step-by-step process; their size and structure are perfectly controlled, and they
      are widely used for biomedical purposes. Previously, we showed that a phosphorous
      based dendrimer capped with anionic AzaBisPhosphonate groups (so-called ABP
      dendrimer) has immunomodulatory and anti-inflammatory properties toward the human
      immune system. It dramatically inhibits the onset and development of experimental
      arthritis in a mouse model relevant for human rheumatoid arthritis, a chronic
      inflammatory disease of auto-immune origin. In this article, we demonstrate in an
      unprecedented study that cynomolgus macaques repeatedly injected with the ABP
      dendrimer displayed no adverse response. Indeed, biochemical, haematological,
      clotting and immunological parameters remained with a normal physiological range
      during the study. Moreover, quantification of serum cytokines and
      histopathological analyses failed to reveal any noticeable lesion or noteworthy
      non-physiological occurrence. These results strengthen the potential of the ABP
      dendrimer as an innovative drug-candidate for the treatment of inflammatory
      diseases and favor the regulatory preclinical development of the molecule.

PMID- 25051331
TI  - Drosophila melanogaster as a model organism to study nanotoxicity.
AB  - Drosophila melanogaster has been used as an in vivo model organism for the study
      of genetics and development since 100 years ago. Recently, the fruit fly
      Drosophila was also developed as an in vivo model organism for toxicology
      studies, in particular, the field of nanotoxicity. The incorporation of
      nanomaterials into consumer and biomedical products is a cause for concern as
      nanomaterials are often associated with toxicity in many in vitro studies. In
      vivo animal studies of the toxicity of nanomaterials with rodents and other
      mammals are, however, limited due to high operational cost and ethical
      objections. Hence, Drosophila, a genetically tractable organism with distinct
      developmental stages and short life cycle, serves as an ideal organism to study
      nanomaterial-mediated toxicity. This review discusses the basic biology of
      Drosophila, the toxicity of nanomaterials, as well as how the Drosophila model
      can be used to study the toxicity of various types of nanomaterials.

PMID- 25051332
TI  - Size dependent toxicity of zinc oxide nano-particles in soil nematode
      Caenorhabditis elegans.
AB  - Zinc oxide nano-particles (ZnO NPs), with their unique physico-chemical
      properties conferred by various size formulations, are extensively used in
      consumer products. The enormous usage coupled with their release to the
      environment demands risk assessment of ZnO NPs on health and the environment.
      Toxicity of ZnO NPs is well understood in comparison to the bulk ZnO. However,
      toxicity in relation to the NP size is poorly understood. In this context, we
      examined the adverse effects of different sizes (35 nm, 50 nm and 100 nm) of ZnO
      NPs in soil nematode C. elegans along with bulk ZnO and ZnCl2. Here, we show that
      growth, reproduction and behavior of worms were adversely affected by ZnO NPs in
      a size dependent manner. Further, exposure to ZnO NPs caused modulation of
      expression/function of genes associated with Insulin/IGF-like signaling pathway
      and/or stress response pathway in a size dependent manner in exposed worms. The
      expression of pro-apoptotic gene and suppression of anti-apoptotic genes,
      together with increased numbers of cell corpses in the germ line, indicated that
      apoptosis was also dependent on the size of the ZnO NP. Taken together, our study
      provides evidence that exposure to ZnO NPs disrupts various physiological
      processes and causes apoptosis in the germ-line even at very low concentration in
      a size dependent manner. Our finding suggests the inclusion of size as an
      additional measure for the cautious monitoring of ZnO NP disposal into the
      environment.

PMID- 25051333
TI  - Diversity and distribution of deep-sea shrimps in the Ross Sea region of
      Antarctica.
AB  - Although decapod crustaceans are widespread in the oceans, only Natantia
      (shrimps) are common in the Antarctic. Because remoteness, depth and ice cover
      restrict sampling in the South Ocean, species distribution modelling is a useful
      tool for evaluating distributions. We used physical specimen and towed camera
      data to describe the diversity and distribution of shrimps in the Ross Sea region
      of Antarctica. Eight shrimp species were recorded: Chorismus antarcticus;
      Notocrangon antarcticus; Nematocarcinus lanceopes; Dendrobranchiata; Pasiphaea
      scotiae; Pasiphaea cf. ledoyeri; Petalidium sp., and a new species of Lebbeus.
      For the two most common species, N. antarcticus and N. lanceopes, we used maximum
      entropy modelling, based on records of 60 specimens and over 1130 observations
      across 23 sites in depths from 269 m to 3433 m, to predict distributions in
      relation to environmental variables. Two independent sets of environmental data
      layers at 0.05 degrees  and 0.5 degrees  resolution respectively, showed how
      spatial resolution affected the model. Chorismus antarcticus and N. antarcticus
      were found only on the continental shelf and upper slopes, while N. lanceopes,
      Lebbeus n. sp., Dendrobranchiata, Petalidium sp., Pasiphaea cf. ledoyeri, and
      Pasiphaea scotiae were found on the slopes, seamounts and abyssal plain. The
      environmental variables that contributed most to models for N. antarcticus were
      depth, chlorophyll-a concentration, temperature, and salinity, and for N.
      lanceopes were depth, ice concentration, seabed slope/rugosity, and temperature.
      The relative ranking, but not the composition of these variables changed in
      models using different spatial resolutions, and the predicted extent of suitable
      habitat was smaller in models using the finer-scale environmental layers. Our
      modelling indicated that shrimps were widespread throughout the Ross Sea region
      and were thus likely to play important functional role in the ecosystem, and that
      the spatial resolution of data needs to be considered both in the use of species
      distribution models. 

PMID- 25051335
TI  - Adsorption of a dihydro-TTF derivative on Au(111) via a thiolate complex bonding
      to gold adatoms.
AB  - A dihydro-TTF derivative with four acetyl-protected thiol ligands was synthesised
      and adsorbed on Au(111) under UHV conditions. Scanning Tunnelling Microscopy
      (STM) and Infrared (IR) spectroscopy show that self-organised structures are
      formed following annealing to 333 K, with each pair of bidentate thiolate ligands
      bonding to a single gold adatom in a S-Auad-S complex. Due to the lack of a
      direct orbital overlap between the dihydro-TTF moieties and the surface,
      relatively little charge transfer between TAT-TTF and the gold surface occurs. 

PMID- 25051337
TI  - Determining the chronology of deposition of natural fingermarks and inks on paper
      using secondary ion mass spectrometry.
AB  - This study thoroughly explores the use of time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) for determining the deposition sequence of fingermarks
      and ink on a porous paper surface. Our experimental work has demonstrated that
      mapping selected endogenous components present in natural fingermarks enables the
      observation of friction ridges on a laser-printed surface, only when a
      fingerprint is deposited over this layer of ink. Further investigations have
      shown limited success on ink-jet printing and ballpoint pen inks. 51 blind tests
      carried out on natural, latent fingermarks on laser-printed surfaces; up to 14th
      depletion with samples aged for up to 421 days have resulted in a 100% success
      rate. Development with ninhydrin was found to affect the fingermark residue
      through mobilisation of ions, therefore sequencing determination was compromised;
      whilst iodine fuming and 1,2-indanedione developers did not. This implied that
      selected development methods affected success in fingermark-ink deposition order
      determination. These results were further corroborated through inter-laboratory
      validation studies. The adopted protocol and extensive series of tests have
      therefore demonstrated the effectiveness and limitations of ToF-SIMS in providing
      chronological sequencing information of fingermarks on questioned documents;
      successfully resolving this order of deposition query.

PMID- 25051336
TI  - Absolute Configuration of a Rare Sesquiterpene: (+)-3-Ishwarone.
AB  - To determine the absolute configuration of 3-ishwarone, the experimental
      electronic circular dichroism (ECD), electronic dissymmetry factor (EDF), optical
      rotatory dispersion (ORD), vibrational circular dichroism (VCD), and vibrational
      dissymmetry factor (VDF) spectra of (+)-3-ishwarone are analyzed with the
      corresponding density functional theoretical predictions for different
      diastereomers. ECD and ORD spectra by themselves could not facilitate the
      determination of the absolute configuration of this molecule. However, the
      magnitude of the experimental EDF of (+)-3-ishwarone is found to match better
      with that predicted for the (1R,2S,4S,5R,9R,11R) diastereomer. The analyses of
      similarity measures between experimental and predicted spectra for VCD and VDF
      clearly suggested that the absolute configuration of (+)-3-ishwarone is
      (1R,2S,4S,5R,9R,11R). 

PMID- 25051338
TI  - Model of EF4-induced ribosomal state transitions and mRNA translocation.
AB  - EF4, a highly conserved protein present in bacteria, mitochondria and
      chloroplasts, can bind to both the posttranslocation and pretranslocation
      ribosomal complexes. When binding to the posttranslocation state, it catalyzes
      backward translocation to a pretranslocation state. When binding to the
      pretranslocation state, it catalyzes transition to another pretranslocation state
      that is similar and possibly identical to that resulting from the
      posttranslocation state bound by EF4, and competes with EF-G to regulate the
      elongation cycle. However, the molecular mechanism on how EF4 induces state
      transitions and mRNA translocation remains unclear. Here, we present both the
      model for state transitions induced by EF4 binding to the posttranslocation state
      and that by EF4 binding to the pretranslocation state, based on which we study
      the kinetics of EF4-induced state transitions and mRNA translocation, giving
      quantitative explanations of the available experimental data. Moreover, we
      present some predicted results on state transitions and mRNA translocation
      induced by EF4 binding to the pretranslocation state complexed with the mRNA
      containing a duplex region. 

PMID- 25051339
TI  - In vivo assessment of printed microvasculature in a bilayer skin graft to treat
      full-thickness wounds.
AB  - Chronic wounds such as diabetic foot ulcers and venous leg ulcers are common
      problems in people suffering from type 2 diabetes. These can cause pain, and
      nerve damage, eventually leading to foot or leg amputation. These types of wounds
      are very difficult to treat and sometimes take months or even years to heal
      because of many possible complications during the process. Allogeneic skin
      grafting has been used to improve wound healing, but the majority of grafts do
      not survive several days after being implanted. We have been studying the
      behavior of fibroblasts and keratinocytes in engineered capillary-like
      endothelial networks. A dermo-epidermal graft has been implanted in an athymic
      nude mouse model to assess the integration with the host tissue as well as the
      wound healing process. To build these networks into a skin graft, a modified
      inkjet printer was used, which allowed the deposit of human microvascular
      endothelial cells. Neonatal human dermal fibroblast cells and neonatal human
      epidermal keratinocytes were manually mixed in the collagen matrix while
      endothelial cells printed. A full-thickness wound was created at the top of the
      back of athymic nude mice and the area was covered by the bilayered graft. Mice
      of the different groups were followed until completion of the specified
      experimental time line, at which time the animals were humanely euthanized and
      tissue samples were collected. Wound contraction improved by up to 10% when
      compared with the control groups. Histological analysis showed the neoskin having
      similar appearance to the normal skin. Both layers, dermis and epidermis, were
      present with thicknesses resembling normal skin. Immunohistochemistry analysis
      showed favorable results proving survival of the implanted cells, and confocal
      images showed the human cells' location in the samples that were collocated with
      the bilayer printed skin graft. 

PMID- 25051340
TI  - Two-week referrals for suspected head and neck cancer: two cycles of audit, 10
      years apart, in a district general hospital.
AB  - OBJECTIVE: To analyse trends in two-week rule referrals for head and neck cancer
      over 10 years. METHOD: Data from two-week referrals received by the Wirral
      University Hospital NHS Trust between 1 January and 30 June 2012 were compared
      with similar data from 2002. RESULTS: A total of 357 referrals were received
      during the 6-month audit period, compared with 149 during the whole of 2002.
      Cancer pick-up rates were 9 per cent and 5 per cent in the first and second
      cycles, respectively. CONCLUSION: The annual number of two-week referrals made to
      our department increased by over 450 per cent in 10 years, but the resulting
      cancer pick-up rate fell by nearly 50 per cent. Whilst cancer patients need to be
      seen quickly, the current system is inefficient in parts. Modifications to the
      treatment pathway should be considered to improve patient care quality and reduce
      pressure on ENT departments.

PMID- 25051341
TI  - The neural mechanisms underlying the acute effect of cigarette smoking on chronic
      smokers.
AB  - Although previous research had related structural changes and impaired cognition
      to chronic cigarette smoking, recent neuroimaging studies have associated
      nicotine, which is a main chemical substance in cigarettes, with improvements in
      cognitive functions (e.g. improved attention performance). However, information
      about the alterations of whole-brain functional connectivity after acute
      cigarette smoking is limited. In this study, 22 smokers underwent resting-state
      functional magnetic resonance imaging (rs-fMRI) after abstaining from smoking for
      12 hours (state of abstinence, SOA). Subsequently, the smokers were allowed to
      smoke two cigarettes (state of satisfaction, SOS) before they underwent a second
      rs-fMRI. Twenty non-smokers were also recruited to undergo rs-fMRI. In addition,
      high-resolution 3D T1-weighted images were acquired using the same magnetic
      resonance imaging(fMRI)scanner for all participants. The results showed that
      smokers had structural changes in insula, thalamus, medial frontal cortex and
      several regions of the default mode network (DMN) compared with non-smokers.
      Voxel-wise group comparisons of newly developed global brain connectivity (GBC)
      showed that smokers in the SOA condition had higher GBC in the insula and
      superior frontal gyrus compared with non-smokers. However, smokers in the SOS
      condition demonstrated significantly lower GBC in several regions of the DMN, as
      compared with smokers in the SOA condition. These results suggest that structural
      integrity combined with dysfunction of the DMN might be involved in relapses
      after a short period of time among smokers. 

PMID- 25051342
TI  - G-quadruplex formation of FXYD1 pre-mRNA indicates the possibility of regulating
      expression of its protein product.
AB  - G-quadruplexes are higher-order nucleic acid structures formed of square-planar
      arrangements of four guanine bases held together by Hoogsteen-type hydrogen
      bonds. Stacks of guanine tetrads are stabilised by intercalating potassium ions.
      FXYD1 encodes for phospholemman, a regulatory subunit of the cardiac Na(+)/K(+)
      ATPase. Computational sequence analysis of FXYD1 pre-mRNA predicted the formation
      of stable intramolecular G-quadruplexes in human and orthologue sequences.
      Multiple sequence alignment indicated that G-rich sequences are conserved in
      evolution suggesting a potential role of G-quadruplexes in FXYD1 gene expression.
      The existence of a non-functional alternative splicing product indicated that the
      G-quadruplex formation may control alternative splicing. Quadruplex formation of
      human and bovine oligonucleotides was confirmed in vitro by native polyacrylamide
      gel electrophoresis and intrinsic fluorescence emission spectroscopy. Taking
      together the evolutionary conservation of G-quadruplex forming sequences with the
      confirmation of G-quadruplex formation in vitro by two FXYD1 homologues the
      results point to a potential role of these structures in regulating the
      expression of FXYD1 and thus regulate indirectly the activity of the cardiac
      Na(+)/K(+)-ATPase. 

PMID- 25051343
TI  - Disrupted calcium homeostasis is involved in elevated zinc ion-induced
      photoreceptor cell death.
AB  - Zinc (Zn), the second abundant trace element in living organisms, plays an
      important role in regulating cell metabolism, signaling, proliferation, gene
      expression and apoptosis. Meanwhile, the overload of Zn will disrupt the
      intracellular calcium homeostasis via impairing mitochondrial function. However,
      the specific molecular mechanism underlying zinc-induced calcium regulation
      remains poorly understood. In the present study, using zinc chloride (ZnCl2) as a
      stressor, we investigated the effect of exogenous Zn(2+) in regulating murine
      photoreceptor cell viability, reactive oxygen species (ROS), cell cycle
      distribution and calcium homeostasis as well as plasma membrane calcium ATPase
      (PMCA) isoforms (PMCA1 and PMCA2, i.e., ATP2B1, ATP2B2) expression. We found that
      the exogenous Zn(2+) in the exposure range (31.25-125.0 MUmol/L) results in the
      overgeneration of ROS, cell cycle arrest at G2/M phases, elevation of cytosolic
      [Ca(2+)], inactivation of Ca(2+)-ATPase and reduction of both PMCA1 and PMCA2 in
      661 W cells, and thus induces cell death. In conclusion, ZnCl2 exposure can
      elevate the cytosolic [Ca(2+)], disrupt the intracellular calcium homeostasis,
      further initiate Ca(2+)-dependent signaling pathway in 661 W cells, and finally
      cause cell death. Our results will facilitate the understanding of cell death
      induced by the zinc ion-mediated calcium homeostasis disruption.

PMID- 25051344
TI  - Investigation on the influence of (Z)-3-(2-(3-chlorophenyl)hydrazono)-5,6
      dihydroxyindolin-2-one (PT2) on beta-amyloid(1-40) aggregation and toxicity.
AB  - In Alzheimer's disease (AD), native Abeta protein monomers aggregate through the
      formation of a variety of water-soluble, toxic oligomers, ultimately leading to
      insoluble fibrillar deposits. The inhibition of oligomers formation and/or their
      dissociation into non-toxic monomers, are considered an attractive strategy for
      the prevention and treatment of AD. A number of studies have demonstrated that
      small molecules, containing single or multiple (hetero)aromatic rings, can
      inhibit protein aggregation, being potentially effective in AD treatment.
      Starting from previously reported data on the antiamyloidogenic activity of a
      series of 3-hydrazonoindolinones, compound PT2 was selected to deeply investigate
      the inhibitory mechanism in the Abeta aggregation cascade. We compared data from
      DLS, NMR, CD, TEM and ThT fluorescence measures to ascertain the interactions
      with amyloidogenic species formed in vitro during the aggregation process, and
      confirmed this feature with cell viability tests on HeLa cultured cells. PT2 was
      effective in disrupting toxic oligomers and mature amyloid fibrils, stabilizing
      Abeta as non-toxic, beta-sheet arranged, ThT-insensitive protofilaments. It also
      strongly reduced cellular toxicity caused by Abeta and showed good antioxidant
      properties in two radical scavenging tests. Taken together, these data confirmed
      that PT2 is a small molecule inhibitor of Abeta oligomerization and toxicity,
      displaying also additional activity as antioxidant. 

PMID- 25051346
TI  - Effect of PTEN and KAI1 gene overexpression on the proliferation, metastasis and
      radiosensitivity of ASPC-1 pancreatic cancer cells under hypoxic conditions.
AB  - The aim of the present study was to investigate the effects of PTEN and KAI1 gene
      overexpression on the proliferation, metastasis and radiosensitivity of ASPC-1
      pancreatic cancer cells under hypoxic conditions. Recombinant vectors that
      overexpress PTEN and KAI1 genes were transfected into hypoxic ASPC-1 cells.
      Protein expression levels were detected by western blot analysis. An MTT cell
      growth curve assay and a colony-forming assay were used to analyze cell
      proliferation, and a Transwell assay was performed to evaluate the metastatic
      ability of the cells. Annexin V flow cytometry was used to determinate the
      apoptotic rate of X-ray-treated ASPC-1 cells. Western blot analysis revealed that
      PTEN- and KAI1-transfected ASPC-1 cells significantly upregulated PTEN and KAI1
      expression. The proliferation of hypoxic ASPC-1 cells was significantly
      suppressed by PTEN and KAI1. Furthermore, PTEN and KAI1 overexpression inhibited
      the metastatic ability of hypoxic ASPC-1 cells. Following X-ray treatment, the
      percentage of apoptotic cells increased significantly in the ASPC-1 cells
      transfected with PTEN and KAI1, which demonstrated that hypoxic ASPC-1 cells were
      more radiosensitive due to PTEN and KAI1 overexpression. In conclusion, double
      overexpression of PTEN and KAI1 inhibited the proliferation and metastatic
      activity, and enhanced apoptosis induced by X-ray in ASPC-1 cells under hypoxic
      conditions, which indicates that PTEN and KAI1 double-expression may have
      valuable application in pancreatic cancer gene therapy.

PMID- 25051345
TI  - Urinating standing versus sitting: position is of influence in men with prostate
      enlargement. A systematic review and meta-analysis.
AB  - BACKGROUND: It is suggested that the body posture during urination can influence
      urodynamic parameters in patients with Lower Urinary Tract Symptoms (LUTS) to an
      extent approaching pharmacological interventions. In this article, the influence
      of body position during micturition on maximum urinary flow rate (Qmax), voiding
      time (TQ) and post-void residual volume (PVR) in healthy males and patients with
      LUTS is analyzed by means of a systematic review and meta-analysis. EVIDENCE
      ACQUISITION: A systematic search was conducted in 14 medical databases. Studies
      comparing urodynamic parameters in standing versus sitting position were eligible
      for inclusion. Studies were stratified according to health status of included
      male participants: healthy individuals and patients with LUTS. Standardized mean
      differences for Qmax, TQ and PVR were pooled in a random effects model. RESULTS:
      Eleven articles were included. In men with LUTS, a significantly lower PVR (
      24.96 ml; 95%CI -48.70 to -1.23) was shown in sitting position compared to
      standing. In accordance, Qmax was increased (1.23 ml/s; 95%CI -1.02 to 3.48), and
      TQ was decreased (-0.62 s; 95%CI -1.66 to 0.42) in sitting position, although
      these differences did not reach statistical significance. In healthy men, Qmax
      (0.18 ml/s; 95% CI -1.67 to 2.02), TQ (0.49 s; 95%CI -3.30 to 4.27) and PVR (0.43
      ml; 95%CI -0.79 to 1,65) were similar in sitting and standing position.
      CONCLUSION: For healthy men, no difference is found in any of the urodynamic
      parameters. In patients with LUTS, the sitting position is linked with an
      improved urodynamic profile.

PMID- 25051347
TI  - Interplay between genetic and clinical variables affecting platelet reactivity
      and cardiac adverse events in patients undergoing percutaneous coronary
      intervention.
AB  - Several clinical and genetic variables are associated with influencing high on
      treatment platelet reactivity (HTPR). The aim of the study was to propose a path
      model explaining a concurrent impact among variables influencing HTPR and
      ischemic events. In this prospective cohort study polymorphisms of CYP2C19*2,
      CYP2C19*17, ABCB1, PON1 alleles and platelet function assessed by Multiple
      Electrode Aggregometry were assessed in 416 patients undergoing percutaneous
      coronary intervention treated with clopidogrel and aspirin. The rates of major
      adverse cardiac events (MACE) were recorded during a 12-month follow up. The path
      model was calculated by a structural equation modelling. Paths from two clinical
      characteristics (diabetes mellitus and acute coronary syndrome (ACS)) and two
      genetic variants (CYP2C19*2 and CYP2C19*17) independently predicted HTPR (path
      coefficients: 0.11 0.10, 0.17, and -0.10, respectively; p<0.05 for all). By use
      of those four variables a novel score for prediction of HTPR was built: in a
      factor-weighted model the risk for HTPR was calculated with an OR of 3.8 (95%CI:
      3.1-6.8, p<0.001) for a score level of >=1 compared with a score of <1. While
      MACE was independently predicted by HTPR and age in the multivariate model (path
      coefficient: 0.14 and 0.13, respectively; p<0.05), the coexistence of HTPR and
      age >=75 years emerged as the strongest predictor of MACE. Our study suggests a
      pathway, which might explain indirect and direct impact of variables on clinical
      outcome: ACS, diabetes mellitus, CYP2C19*2 and CYP2C19*17 genetic variants
      independently predicted HTPR. In turn, age >=75 years and HTPR were the strongest
      predictors of MACE. 

PMID- 25051349
TI  - Water oxidation electrocatalysis by a zeolitic imidazolate framework.
AB  - The search for efficient water oxidation catalysts (WOCs) is of paramount
      importance in energy and environmental fields, but there exists no good non-noble
      catalyst that works under acidic and alkaline conditions. Intensive
      investigations have recently focused on cobalt based complex/solid catalysts.
      Here, we have introduced a new type of cobalt-based WOC made of metal-organic
      frameworks where the redox function of cobalt centres was modified by imidazolate
      linkers for facilitating the proton transfer process. This cobalt-containing
      zeolitic imidazolate framework (Co-ZIF-9) has been demonstrated for the first
      time to electrocatalyze the oxygen evolution reaction in a wide pH range. The
      catalyst was found by theoretical calculation to be capable of activating the
      water molecule via binding the OH-group to the metal sites with low activation
      barriers, while the eliminated proton was accepted by the nearby benzimidazolate
      motifs. This allows Co-ZIF-9 to work effectively for the electrochemical oxygen
      evolution reaction. 

PMID- 25051348
TI  - Sex- and smoke-related differences in gastrointestinal transit of cyclosporin A
      microemulsion capsules.
AB  - The aim of this work was to study the effect of the sex and the smoking status on
      the pharmacokinetics and the bioequivalence assessment of a branded and a generic
      cyclosporine A microemulsion formulation in soft-gelatin capsule. Sixteen healthy
      volunteers (eight women and eight men) participated in a CyA bioequivalence
      study, with nine of the volunteers being smokers. Sandimmun Neoral(r) (brand
      formulation; Reference) and Sigmasporin Microral(r) (generic formulation; Test)
      were administered under fasting conditions. Pharmacokinetic parameters were
      calculated through non compartmental analysis. Bioequivalence was declared based
      on the 90% confidence intervals (90% CI) for the T/R ratio of the geometric means
      for each parameter. In vitro determination of the capsules opening time was
      performed in simulated gastric fluid without enzyme with USP Apparatus 2. The
      extent of absorption was similar between both products for all subjects or each
      sex-group. The absorption rate was similar for both products when considering all
      subjects, whereas a significant difference in the TMAX between the two products
      was observed for the male subjects only, which relates to its slower capsule
      opening time observed in vitro (12.4 versus 6.0 min). No differences were
      observed in women that could relate to their slower gastric emptying. Differences
      in drug exposure were observed between smokers and non-smokers. Sex- and smoke
      related differences in the gastrointestinal transit should be considered when the
      on-set time would be determinant for the treatment success of a drug.

PMID- 25051334
TI  - Inhibin at 90: from discovery to clinical application, a historical review.
AB  - When it was initially discovered in 1923, inhibin was characterized as a
      hypophysiotropic hormone that acts on pituitary cells to regulate pituitary
      hormone secretion. Ninety years later, what we know about inhibin stretches far
      beyond its well-established capacity to inhibit activin signaling and suppress
      pituitary FSH production. Inhibin is one of the major reproductive hormones
      involved in the regulation of folliculogenesis and steroidogenesis. Although the
      physiological role of inhibin as an activin antagonist in other organ systems is
      not as well defined as it is in the pituitary-gonadal axis, inhibin also
      modulates biological processes in other organs through paracrine, autocrine,
      and/or endocrine mechanisms. Inhibin and components of its signaling pathway are
      expressed in many organs. Diagnostically, inhibin is used for prenatal screening
      of Down syndrome as part of the quadruple test and as a biochemical marker in the
      assessment of ovarian reserve. In this review, we provide a comprehensive summary
      of our current understanding of the biological role of inhibin, its relationship
      with activin, its signaling mechanisms, and its potential value as a diagnostic
      marker for reproductive function and pregnancy-associated conditions. 

PMID- 25051350
TI  - Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in
      colorectal cancer through ERK and beta-arrestin pathways.
AB  - The CXC chemokine receptor 7 (CXCR7) has been reported to be involved in cell
      growth, metastasis and apoptosis in certain cancers. However, the function and
      molecular mechanisms of CXCR7 in human colorectal cancer (CRC) are still
      undefined. In the present study, sixty-eight cases of CRC tissues and
      corresponding adjacent non-cancer tissues (ANCT) were collected, and the
      expression of CXCR7 was assessed using immunohistochemistry (IHC) in biopsy
      samples. Furthermore, CXCR7 gene was silenced by small hairpin RNA-mediated
      lentiviral vector (Lv-shCXCR7), by transfection into human CRC cells (SW480 and
      HT-29). The levels of p-ERK, beta-arrestin, proliferating cell nuclear antigen
      (PCNA), matrix metallopeptidase-2 (MMP-2) and caspase-3 (CAS-3) were detected by
      western blotting. Cell proliferative activities and invasive capability were
      respectively measured by MTT and Transwell assays. Cell apoptosis was analyzed by
      flow cytometry. The results demonstrated that CXCR7 expression was significantly
      upregulated in CRC tissues compared with the ANCT (54.4 vs. 36.8%, P=0.041), and
      correlated with Dukes staging and depth of invasion (P=0.007; P=0.002). Silencing
      of CXCR7 gene suppressed cell proliferation and invasion, and induced cell
      apoptosis in CRC cells with decreased expression of p-ERK, beta-arrestin, PCNA
      and MMP-2 but increased expression of CAS-3. The tumor volumes in the SW480
      subcutaneous tumor models treated with Lv-shCXCR7 were significantly smaller than
      those of the negative control (NC) and PBS groups (P<0.01). In conclusion, our
      findings indicate that upregulation of CXCR7 expression is associated with tumor
      invasion, and silencing of the CXCR7 gene represses the development of CRC cells
      through ERK and beta-arrestin pathways, suggesting that CXCR7 may serve as a
      potential therapeutic target for the treatment of CRC. 

PMID- 25051351
TI  - Antibiotic treatment of ventilator-associated tracheobronchitis: to treat or not
      to treat?
AB  - PURPOSE OF REVIEW: To evaluate the data on antimicrobial therapy for ventilator
      associated tracheobronchitis (VAT) to prevent ventilator-associated pneumonia
      (VAP), and its impact on patient outcomes. RECENT FINDINGS: Mechanically
      ventilated patients are at increased risk for tracheal colonization with
      bacterial pathogens that may progress to VAT and/or VAP. Previous studies suggest
      that 10-30% of patients with VAT progress to VAP, which results in increased
      morbidity but not mortality. Several natural history studies and small randomized
      controlled trials and a meta-analysis reported that appropriate, pre-emptive
      antibiotic treatment for VAT reduces VAP, duration of intubation and length of
      ICU stay. SUMMARY: This review focuses on diagnostic criteria for VAT and VAP,
      etiologic agents, rationale and benefits of initiating pre-emptive, appropriate
      antibiotic treatment for VAT to prevent VAP, improve patient outcomes and
      associated acute and chronic healthcare costs.

PMID- 25051352
TI  - Effect of increasing total solids contents on anaerobic digestion of food waste
      under mesophilic conditions: performance and microbial characteristics analysis.
AB  - The total solids content of feedstocks affects the performances of anaerobic
      digestion and the change of total solids content will lead the change of
      microbial morphology in systems. In order to increase the efficiency of anaerobic
      digestion, it is necessary to understand the role of the total solids content on
      the behavior of the microbial communities involved in anaerobic digestion of
      organic matter from wet to dry technology. The performances of mesophilic
      anaerobic digestion of food waste with different total solids contents from 5% to
      20% were compared and the microbial communities in reactors were investigated
      using 454 pyrosequencing technology. Three stable anaerobic digestion processes
      were achieved for food waste biodegradation and methane generation. Better
      performances mainly including volatile solids reduction and methane yield were
      obtained in the reactors with higher total solids content. Pyrosequencing results
      revealed significant shifts in bacterial community with increasing total solids
      contents. The proportion of phylum Chloroflexi decreased obviously with
      increasing total solids contents while other functional bacteria showed
      increasing trend. Methanosarcina absolutely dominated in archaeal communities in
      three reactors and the relative abundance of this group showed increasing trend
      with increasing total solids contents. These results revealed the effects of the
      total solids content on the performance parameters and the behavior of the
      microbial communities involved in the anaerobic digestion of food waste from wet
      to dry technologies. 

PMID- 25051354
TI  - Photoisomerisation and ligand-controlled reversible aggregation of azobenzene
      functionalised gold nanoparticles.
AB  - The photochemical behaviour of functionalised gold nanoparticles (AuNPs) carrying
      azobenzenethiolate-alkylthiolate monolayers was investigated. Repeated trans-cis
      and cis-trans isomerisation cycles could be performed in all cases with high
      efficiency. Reversible photoinduced aggregation was observed when azothiolates
      with long alkyl spacers (>=C7) were combined with short (C5) alkylthiolate
      coligands. The choice of a coligand thus offers control over the aggregation
      properties of the nanoparticles. 

PMID- 25051353
TI  - Health outcome after major trauma: what are we measuring?
AB  - IMPORTANCE: Trauma is a global disease and is among the leading causes of
      disability in the world. The importance of outcome beyond trauma survival has
      been recognised over the last decade. Despite this there is no internationally
      agreed approach for assessment of health outcome and rehabilitation of trauma
      patients. OBJECTIVE: To systematically examine to what extent outcomes measures
      evaluate health outcomes in patients with major trauma. DATA SOURCES: MEDLINE,
      EMBASE, and CINAHL (from 2006-2012) were searched for studies evaluating health
      outcome after traumatic injuries. STUDY SELECTION AND DATA EXTRACTION: Studies of
      adult patients with injuries involving at least two body areas or organ systems
      were included. Information on study design, outcome measures used, sample size
      and outcomes were extracted. The World Health Organisation International
      Classification of Function, Disability and Health (ICF) were used to evaluate to
      what extent outcome measures captured health impacts. RESULTS: 34 studies from
      755 studies were included in the review. 38 outcome measures were identified. 21
      outcome measures were used only once and only five were used in three or more
      studies. Only 6% of all possible health impacts were captured. Concepts related
      to activity and participation were the most represented but still only captured
      12% of all possible concepts in this domain. Measures performed very poorly in
      capturing concepts related to body function (5%), functional activities (11%) and
      environmental factors (2%). CONCLUSION: Outcome measures used in major trauma
      capture only a small proportion of health impacts. There is no inclusive
      classification for measuring disability or health outcome following trauma. The
      ICF may provide a useful framework for the development of a comprehensive health
      outcome measure for trauma care.

PMID- 25051355
TI  - Comparison of respiratory muscles activity and exercise capacity in patients with
      idiopathic scoliosis and healthy individuals.
AB  - PURPOSE: Idiopathic scoliosis causes respiratory muscles weakness and reduced
      exercise capacity. However, the mechanism of these symptoms is still unknown. The
      main objective of this study was to determine the intensity of respiratory muscle
      activity and exercise capacity in patients with idiopathic scoliosis in
      comparison with healthy people. SUBJECTS: In this study, 20 female patients with
      adult idiopathic scoliosis (10 mild and 10 moderate) as well as 10 healthy
      matched individuals with characteristics of the patients were selected. METHODS:
      The subjects were fatigued through a maximal incremental cycle ergometry
      protocol. Meanwhile, the electromyography values of the external intercostal
      muscles and diaphragm were recorded bilaterally, and fatigue duration was
      determined. RESULTS: The root mean square of concave external intercostal muscles
      and concave diaphragm in patients with idiopathic scoliosis was significantly
      reduced during the fatiguing exercise protocol compared with healthy individuals.
      The median frequencies of the two sides differed significantly and were lower in
      patients with moderate scoliosis than healthy subjects. Fatigue duration
      (minutes) also was lower in patients with moderate scoliosis than healthy
      subjects. CONCLUSIONS: Scoliosis causes respiratory muscle weakness and reduced
      fatigue duration in response to mild physical activity compared with healthy
      subjects and these dysfunctions appear to be related to the severity of scoliosis
      curvature (moderate > mild).

PMID- 25051357
TI  - Unique origin of eye canal combines elements of blood, lymph tube development.

PMID- 25051356
TI  - Quantitative ultrasound characterization of tumor cell death: ultrasound
      stimulated microbubbles for radiation enhancement.
AB  - The aim of this study was to assess the efficacy of quantitative ultrasound
      imaging in characterizing cancer cell death caused by enhanced radiation
      treatments. This investigation focused on developing this ultrasound modality as
      an imaging-based non-invasive method that can be used to monitor therapeutic
      ultrasound and radiation effects. High-frequency (25 MHz) ultrasound was used to
      image tumor responses caused by ultrasound-stimulated microbubbles in combination
      with radiation. Human prostate xenografts grown in severe combined
      immunodeficiency (SCID) mice were treated using 8, 80, or 1000 uL/kg of
      microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to
      0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours
      after treatment. Spectral analysis of images acquired from treated tumors
      revealed overall increases in ultrasound backscatter intensity and the spectral
      intercept parameter. The increase in backscatter intensity compared to the
      control ranged from 1.9+/-1.6 dB for the clinical imaging dose of microbubbles (8
      uL/kg, 250 kPa, 2 Gy) to 7.0+/-4.1 dB for the most extreme treatment condition
      (1000 uL/kg, 750 kPa, 8 Gy). In parallel, in situ end-labelling (ISEL) staining,
      ceramide, and cyclophilin A staining demonstrated increases in cell death due to
      DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a
      result of cell membrane permeabilization, respectively. Quantitative ultrasound
      results indicated changes that paralleled increases in cell death observed from
      histology analyses supporting its use for non-invasive monitoring of cancer
      treatment outcomes. 

PMID- 25051258
TI  - Impact of chronic kidney disease on use of evidence-based therapy in stable
      coronary artery disease: a prospective analysis of 22,272 patients.
AB  - PURPOSE: To assess the frequency of chronic kidney disease (CKD), define the
      associated demographics, and evaluate its association with use of evidence-based
      drug therapy in a contemporary global study of patients with stable coronary
      artery disease. METHODS: 22,272 patients from the ProspeCtive observational
      LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY)
      were included. Baseline estimated glomerular filtration rate (eGFR) was
      calculated (CKD-Epidemiology Collaboration formula) and patients categorised
      according to CKD stage: >89, 60-89, 45-59 and <45 mL/min/1.73 m2. RESULTS: Mean
      (SD) age was 63.9+/-10.4 years, 77.3% were male, 61.8% had a history of
      myocardial infarction, 71.9% hypertension, 30.4% diabetes and 75.4%
      dyslipidaemia. Chronic kidney disease (eGFR<60 mL/min/1.73 m2) was seen in 22.1%
      of the cohort (6.9% with eGFR<45 mL/min/1.73 m2); lower eGFR was associated with
      increasing age, female sex, cardiovascular risk factors, overt vascular disease,
      other comorbidities and higher systolic but lower diastolic blood pressure. High
      use of secondary prevention was seen across all CKD stages (overall 93.4% lipid
      lowering drugs, 95.3% antiplatelets, 75.9% beta-blockers). The proportion of
      patients taking statins was lower in patients with CKD. Antiplatelet use was
      significantly lower in patients with CKD whereas oral anticoagulant use was
      higher. Angiotensin-converting enzyme inhibitor use was lower (52.0% overall) and
      inversely related to declining eGFR, whereas angiotensin-receptor blockers were
      more frequently prescribed in patients with reduced eGFR. CONCLUSIONS: Chronic
      kidney disease is common in patients with stable coronary artery disease and is
      associated with comorbidities. Whilst use of individual evidence-based
      medications for secondary prevention was high across all CKD categories, there
      remains an opportunity to improve the proportion who take all three classes of
      preventive therapies. Angiotensin-converting enzyme inhibitors were used less
      frequently in lower eGRF categories. Surprisingly the reverse was seen for
      angiotensin-receptor blockers. Further evaluation is required to fully understand
      these associations. The CLARIFY (ProspeCtive observational LongitudinAl RegIstry
      oF patients with stable coronary arterY disease) Registry is registered in the
      ISRCTN registry of clinical trials with the number ISRCTN43070564.
      http://www.controlled-trials.com/ISRCTN43070564.

PMID- 25051358
TI  - Bioinformatic analysis of nematode migration-associated genes identifies novel
      vertebrate neural crest markers.
AB  - Neural crest cells are highly motile, yet a limited number of genes governing
      neural crest migration have been identified by conventional studies. To test the
      hypothesis that cell migration genes are likely to be conserved over large
      evolutionary distances and from diverse tissues, we searched for vertebrate
      homologs of genes important for migration of various cell types in the
      invertebrate nematode and examined their expression during vertebrate neural
      crest cell migration. Our systematic analysis utilized a combination of
      comparative genomic scanning, functional pathway analysis and gene expression
      profiling to uncover previously unidentified genes expressed by premigratory,
      emigrating and/or migrating neural crest cells. The results demonstrate that
      similar gene sets are expressed in migratory cell types across distant animals
      and different germ layers. Bioinformatics analysis of these factors revealed
      relationships between these genes within signaling pathways that may be important
      during neural crest cell migration. 

PMID- 25051359
TI  - A unique mono- and diacylglycerol lipase from Penicillium cyclopium: heterologous
      expression, biochemical characterization and molecular basis for its substrate
      selectivity.
AB  - A cDNA gene encoding a mature peptide of the mono- and diacylglycerol lipase
      (abbreviated to PcMdl) from Penicillium cyclopium PG37 was cloned and expressed
      in Pichia pastoris GS115. The recombinant PcMdl (rePcMdl) with an apparent
      molecular weight of 39 kDa showed the highest activity (40.5 U/mL of culture
      supernatant) on 1,2-dibutyrin substrate at temperature 35 degrees C and pH 7.5.
      The rePcMdl was stable at a pH range of 6.5-9.5 and temperatures below 35 degrees
      C. The activity of rePcMdl was inhibited by Hg2+ and Fe3+, but not significantly
      affected by EDTA or the other metal ions such as Na+, K+, Li+, Mg2+, Zn2+, Ca2+,
      Mn2+, Cu2+, and Fe2+. PcMdl was identified to be strictly specific to mono- and
      diacylglycerol, but not triacylglycerol. Stereographic view of PcMdl docked with
      substrate (tri- or diacylglycerol) analogue indicated that the residue Phe256
      plays an important role in conferring the substrate selectivity. Phe256 projects
      its side chain towards the substrate binding groove and makes the sn-1 moiety
      difficult to insert in. Furthermore, sn-1 moiety prevents the phosphorus atom
      (substitution of carboxyl carbon) from getting to the Ogamma of Ser145, which
      results in the failure of triacylglycerol hydrolysis. These results should
      provide a basis for molecular engineering of PcMdl and expand its applications in
      industries. 

PMID- 25051361
TI  - High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc
      and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on
      cell cycle.
AB  - Myc (c-Myc) counteracts p27 effects, and low p27 usually correlates with high Myc
      expression in human cancer. However there is no information on the co-expression
      of both genes in chronic lymphocytic leukemia (CLL). We found a lack of
      correlation between RNA and protein levels of p27 and Myc in CLL cells, so we
      determined the protein levels by immunoblot in 107 cases of CLL. We observed a
      high p27 protein expression in CLL compared to normal B cells. Ectopic p27
      expression in a CLL-derived cell line resulted in cell death resistance.
      Surprisingly, Myc expression was very low or undetectable in most CLL cases
      analyzed, with a clear correlation between high p27 and low Myc protein levels.
      This was associated with low Skp2 expression, which is consistent with the Skp2
      role in p27 degradation and with SKP2 being a Myc target gene. High Myc
      expression did not correlate with leukemia progression, despite that cell cycle
      related Myc target genes were upregulated. However, biochemical analysis showed
      that the high p27 levels inhibited cyclin-Cdk complexes even in Myc expressing
      CLL cells. Our data suggest that the combination of high p27 and low Myc is a
      marker of CLL cells which is mediated by Skp2. 

PMID- 25051362
TI  - Adiponectin promotes pancreatic cancer progression by inhibiting apoptosis via
      the activation of AMPK/Sirt1/PGC-1alpha signaling.
AB  - Adiponectin is an adipocyte-secreted adipokine with pleiotropic actions. Clinical
      evidence has shown that serum adiponectin levels are increased and that
      adiponectin can protect pancreatic beta cells against apoptosis, which suggests
      that adiponectin may play an anti-apoptotic role in pancreatic cancer (PC). Here,
      we investigated the effects of adiponectin on PC development and elucidated the
      underlying molecular mechanisms. Adiponectin deficiency markedly attenuated
      pancreatic tumorigenesis in vivo. We found that adiponectin significantly
      inhibited the apoptosis of both human and mouse pancreatic cancer cells via
      adipoR1, but not adipoR2. Furthermore, adiponectin can increase AMP-activated
      protein kinase (AMPK) phosphorylation and NAD-dependent deacetylase sirtuin-1
      (Sirt1) of PC cells. Knockdown of AMPK or Sirt1 can increase the apoptosis in PC
      cells. AMPK up-regulated Sirt1, and Sirt1 can inversely phosphorylate AMPK.
      Further studies have shown that Sirt1 can deacetylate peroxisome proliferator
      activated receptor gamma coactivator 1-alpha (PGC1alpha), which can increase the
      expression levels of mitochondrial genes. Thus, adiponectin exerts potent anti
      apoptotic effects on PC cells via the activation of AMPK/Sirt1/PGC1alpha
      signaling. Finally, adiponectin can elevate beta-catenin levels. Taken together,
      these novel findings reveal an unconventional role of adiponectin in promoting
      pancreatic cancers, and suggest that the effects of adiponectin on tumorigenesis
      are highly tissue-dependent. 

PMID- 25051363
TI  - Thrombospondin 1 promotes an aggressive phenotype through epithelial-to
      mesenchymal transition in human melanoma.
AB  - Epithelial-to-mesenchymal transition (EMT), in which epithelial cells loose their
      polarity and become motile mesenchymal cells, is a determinant of melanoma
      metastasis. We compared gene expression signatures of mesenchymal-like melanoma
      cells with those of epithelial-like melanoma cells, and identified Thrombospondin
      1 (THBS1) as highly up-regulated in the mesenchymal phenotype. This study
      investigated whether THBS1, a major physiological activator of transforming
      growth factor (TGF)-beta, is involved in melanoma EMT-like process. We sought to
      examine expression patterns in distinct melanoma phenotypes including invasive,
      de-differentiated, label-retaining and drug resistant populations that are
      putatively associated with an EMT-like process. Here we show that THBS1
      expression and secretion was elevated in melanoma cells exhibiting invasive, drug
      resistant, label retaining and mesenchymal phenotypes and correlated with reduced
      expression of genes involved in pigmentation. Elevated THBS1 levels were detected
      in Vemurafenib resistant melanoma cells and inhibition of THBS1 led to
      significantly reduced chemoresistance in melanoma cells. Notably, siRNA-mediated
      silencing of THBS1 and neutralizing antibody to THBS1 reduced invasion in
      mesenchymal-like melanoma cells, while ectopic THBS1 expression in epithelial
      like melanoma cells enhanced invasion. Furthermore, the loss of THBS1 inhibited
      in vivo motility of melanoma cells within the embryonic chicken neural tube. In
      addition, we found aberrant THBS1 protein expression in metastatic melanoma tumor
      biopsies. These results implicate a role for THBS1 in EMT, and hence THBS1 may
      serve as a novel target for strategies aimed at the treatment of melanoma
      invasion and drug resistance.

PMID- 25051360
TI  - Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer:
      possibilities for therapeutic intervention.
AB  - The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant
      transformation, prevention of apoptosis, drug resistance and metastasis. The
      expression of this pathway is frequently altered in breast cancer due to
      mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1,
      PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In
      some breast cancer cases, mutations at certain components of this pathway (e.g.,
      PIK3CA) are associated with a better prognosis than breast cancers lacking these
      mutations. The expression of this pathway and upstream HER2 has been associated
      with breast cancer initiating cells (CICs) and in some cases resistance to
      treatment. The anti-diabetes drug metformin can suppress the growth of breast
      CICs and herceptin-resistant HER2+ cells. This review will discuss the importance
      of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but
      will also include relevant examples from other cancer types. The targeting of
      this pathway will be discussed as well as clinical trials with novel small
      molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in
      breast cancer will be reviewed in association with suppression of the
      EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.

PMID- 25051364
TI  - Macrophages are recruited to hypoxic tumor areas and acquire a pro-angiogenic M2
      polarized phenotype via hypoxic cancer cell derived cytokines Oncostatin M and
      Eotaxin.
AB  - TAMs, a unique and distinct M2-skewed myeloid population of tumor stroma,
      exhibiting pro-tumor functions is fast emerging as a potential target for anti
      cancer immunotherapy. Macrophage-recruitment and M2-polarization represent key
      TAMs-related phenomenon that are amenable to therapeutic intervention. However
      successful translation of these approaches into effective therapeutic regimen
      requires better characterization of tumor-microenvironment derived signals that
      regulate macrophage recruitment and their polarization. Owing to hypoxic milieu
      being a persistent feature of tumor-microenvironment and a major contributor to
      malignancy and treatment resistance, the current study was planned with an aim to
      decipher tumor cell responses to hypoxia vis-a-vis macrophage homing and
      phenotype switching. Here, we show that hypoxia-primed cancer cells chemoattract
      and polarize macrophages to pro-angiogenic M2-polarized subtype via Eotaxin and
      Oncostatin M. Concordantly, hypoxic regions of human breast-cancer specimen
      exhibited elevated Eotaxin and Oncostatin M levels with concurrently elevated M2
      macrophage content. Blockade of Eotaxin/Oncostatin M not only prevented hypoxic
      breast-cancer cells from recruiting and polarizing macrophages towards an M2
      polarized phenotype and retarded tumor progression in 4T1/BALB/c-syngenic-mice
      model of breast-cancer but also enhanced the efficacy of anti-angiogenic
      Bevacizumab. The findings established these two cytokines as novel targets for
      devising effective anticancer therapy particularly for tumors that are refractory
      or develop resistance to anti-angiogenic therapeutics.

PMID- 25051365
TI  - Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent
      for optical imaging in cancer.
AB  - Tumor Endothelial Marker-1 (TEM1/CD248) is a tumor vascular marker with high
      therapeutic and diagnostic potentials. Immuno-imaging with TEM1-specific
      antibodies can help to detect cancerous lesions, monitor tumor responses, and
      select patients that are most likely to benefit from TEM1-targeted therapies. In
      particular, near infrared(NIR) optical imaging with biomarker-specific antibodies
      can provide real-time, tomographic information without exposing the subjects to
      radioactivity. To maximize the theranostic potential of TEM1, we developed a
      panel of all human, multivalent Fc-fusion proteins based on a previously
      identified single chain antibody (scFv78) that recognizes both human and mouse
      TEM1. By characterizing avidity, stability, and pharmacokinectics, we identified
      one fusion protein, 78Fc, with desirable characteristics for immuno-imaging
      applications. The biodistribution of radiolabeled 78Fc showed that this antibody
      had minimal binding to normal organs, which have low expression of TEM1. Next, we
      developed a 78Fc-based tracer and tested its performance in different TEM1
      expressing mouse models. The NIR imaging and tomography results suggest that the
      78Fc-NIR tracer performs well in distinguishing mouse- or human-TEM1 expressing
      tumor grafts from normal organs and control grafts in vivo. From these results we
      conclude that further development and optimization of 78Fc as a TEM1-targeted
      imaging agent for use in clinical settings is warranted. 

PMID- 25051366
TI  - Chronic treatment with cisplatin induces replication-dependent sister chromatid
      recombination to confer cisplatin-resistant phenotype in nasopharyngeal
      carcinoma.
AB  - Cisplatin can cause intrastrand and interstrand crosslinks between purine bases
      and is a chemotherapeutic drug widely used to treat cancer. However, the major
      barrier to the efficacy of the treatment is drug resistance. Homologous
      recombination (HR) plays a central role in restoring stalled forks caused by DNA
      lesions. Here, we report that chronic treatment with cisplatin induces HR to
      confer cisplatin resistance in nasopharyngeal carcinoma (NPC) cells. A high
      frequency of sister chromatid exchanges (SCE) occurs in the cisplatin-resistant
      NPC cells. In addition, several genes in the Fanconi anemia (FA) and template
      switching (TS) pathways show elevated expression. Significantly, depletion of HR
      gene BRCA1, TS gene UBC13, or FA gene FANCD2 suppresses SCE and causes cells to
      accumulate in the S phase, concomitantly with high gammaH2AX foci formation in
      the presence of low-dose cisplatin. Consistent with this result, depletion of
      several genes in the HR, TS, or FA pathway sensitizes the cisplatin-resistant NPC
      cells to cisplatin. Our results suggest that the enhanced HR, in coordination
      with the FA and TS pathways, underlies the cisplatin resistance. Targeting the
      HR, TS, or FA pathways could be a potential therapeutic strategy for treating
      cisplatin-resistant cancer. 

PMID- 25051368
TI  - Cdc6 cooperates with c-Myc to promote genome instability and epithelial to
      mesenchymal transition EMT in zebrafish.
AB  - Aberration in DNA replication is a major cause to genome instability that is a
      hallmark of cancer cells. Cell division cycle 6 (Cdc6) and c-Myc have a critical
      role in the initiation of DNA replication. However, whether their interaction
      induces epithelial-mesenchymal transition (EMT) and promotes tumorigenesis in in
      vivo animal model remains unclear. Since using zebrafish as a cancer model has
      been restricted by the late onset of tumorigenesis and extreme difficulty in
      transformation on skin, we tried to establish a novel non-melanoma skin model in
      zebrafish to study their role in tumorigenesis. A stable transgenic zebrafish was
      created by using tol2 transposon, in which cdc6 and c-myc were co-overexpressed
      in epidermis driven by a skin-specific krt4 promoter. Intriguingly, co
      overexpression of cdc6 and c-myc in transgenic zebrafish skin triggered tumor
      like transformation, apoptosis attenuation, genomic instability, and EMT,
      hallmarks of malignant tumorigenesis. Our findings and other characteristics of
      zebrafish, including optical clarity and small molecule treatment, provide the
      future utility of this model for easy and non-invasive detection and for
      identification of new anti-cancer drug. 

PMID- 25051367
TI  - Overexpression of HMGB1 in melanoma predicts patient survival and suppression of
      HMGB1 induces cell cycle arrest and senescence in association with p21
      (Waf1/Cip1) up-regulation via a p53-independent, Sp1-dependent pathway.
AB  - Although laboratory studies have implicated the high mobility group box 1 (HMGB1)
      in melanoma, its clinical relevance remains unclear. We analyzed nearly 100 cases
      of human melanoma and found that HMGB1 was highly overexpressed in melanoma
      samples relative to normal skin and nevi tissues. Significantly, higher levels of
      HMGB1 correlated with more advanced disease stages and with poorer survival in
      melanoma patients. Unlike the well-documented pro-inflammatory role of the
      extracellular HMGB1, we found that its intracellular activity is necessary for
      melanoma cell proliferation. An absolute dependency of melanoma cell
      proliferation on HMGB1 was underscored by the marked response of cell cycle
      arrest and senescence to HMGB1 knockdown. We demonstrated that HMGB1 deficiency
      induced inhibition of cell proliferation was mediated by p21, which was induced
      via a Sp1-dependent mechanism. Taken together, our data demonstrate a novel
      oncogenic role of HMGB1 in promoting human melanoma cell proliferation and have
      important implications in melanoma patient care. 

PMID- 25051369
TI  - The small heat shock protein B8 (HSPB8) confers resistance to bortezomib by
      promoting autophagic removal of misfolded proteins in multiple myeloma cells.
AB  - Velcade is one of the inescapable drug to treat patient suffering from multiple
      myeloma (MM) and resistance to this drug represents a major drawback for
      patients. However, the mechanisms underlying velcade resistance remain
      incompletely understood. We derived several U266 MM cell clones that resist to
      velcade. U266-resistant cells were resistant to velcade-induced cell death but
      exhibited a similar sensitivity to various proapoptotic stimuli. Careful analysis
      of proteosomal subunits and proteasome enzymatic activities showed that neither
      the composition nor the activity of the proteasome was affected in velcade
      resistant cells. Elimination of velcade-induced poly-ubiquitinated proteins and
      protein aggregates was drastically stimulated in the resistant cells and
      correlated with increased cell survival. Inhibition of the lysosomal activity in
      velcade-resistant cells resulted in an increase of cell aggregates and decrease
      survival, indicating that aggregates are eliminated through lysosomal
      degradation. In addition, pangenomic profiling of velcade-sensitive and resistant
      cells showed that the small heat shock protein HSPB8 was overexpressed in
      resistant cells. Finally, gain and loss of function experiment demonstrated that
      HSPB8 is a key factor for velcade resistance. In conclusion, HSPB8 plays an
      important role for the elimination of aggregates in velcade-resistant cells that
      contributes to their enhanced survival. 

PMID- 25051370
TI  - Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS
      nanovesicles on brain tumors.
AB  - Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary
      (metastatic), remain among the most intractable and fatal of all cancers. We have
      shown that nanovesicles consisting of Saposin C (SapC) and
      dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer
      cells both in vitro and in vivo. These actions are a consequence of the affinity
      of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in
      the outer membrane of a variety of tumor cells and tumor-associated vasculature.
      In this study, we first characterize SapC-DOPS bioavailability and antitumor
      effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity
      towards phosphatidylserine by showing that glioblastoma targeting is abrogated
      after in vivo exposure to lactadherin, which binds phosphatidylserine with high
      affinity. Second, we demonstrate that SapC-DOPS selectively targets brain
      metastases-forming cancer cells both in vitro, in co-cultures with human
      astrocytes, and in vivo, in mouse models of brain metastases derived from human
      breast or lung cancer cells. Third, we demonstrate that SapC-DOPS have cytotoxic
      activity against metastatic breast cancer cells in vitro, and prolong the
      survival of mice harboring brain metastases. Taken together, these results
      support the potential of SapC-DOPS for the diagnosis and therapy of primary and
      metastatic brain tumors. 

PMID- 25051371
TI  - Preoperative chemotherapy prior to pulmonary metastasectomy in surgically
      resected primary colorectal carcinoma.
AB  - BACKGROUND: The benefit of preoperative chemotherapy prior to pulmonary
      metastasectomy for patients with colorectal carcinoma (CRC) is unknown. Here, we
      identify outcomes of preoperative chemotherapy in patients with resected primary
      CRC who then underwent pulmonary metastasectomy. METHODS: We queried a
      prospective database to identify treatment characteristics. Multivariate analyses
      identified predictors of overall survival (OS) and progression-free survival
      (PFS). RESULTS: 229 patients underwent lung metastasectomy, of whom 115 proceeded
      to surgery without chemotherapy while 114 received preoperative regimen based on
      oxaliplatin (32%), irinotecan (46%), capecitabine (16%), or other (6%). Median
      PFS in preoperative chemotherapy vs. surgery alone arms were comparable
      (p=0.004). Patients on oxaliplatin-based therapy had an improved OS vs. an
      irinotecan, capecitabine, or alternate regimen (p=.019). On multivariate
      analysis, the irinotecan subset had a worse OS (HR 1.846; 95% CI 1.070, 3.185)
      vs. surgery alone arm (p=0.028). The OS of an oxaliplatin-based regimen vs. no
      chemotherapy was inconclusive (HR 0.57; 95% CI 0.237 to 1.389, p=0.218).
      Multivariate analysis demonstrated a worse PFS and OS for the male gender and an
      incomplete resection (R2). CONCLUSION: Prospective trials on specific
      preoperative regimens and criteria for patient selection may identify a role for
      preoperative chemotherapy prior to a curative pulmonary metastasectomy.

PMID- 25051372
TI  - Genome-wide DNA methylation and gene expression patterns provide insight into
      polycystic ovary syndrome development.
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in
      women. However, the epigenetic mechanism involved in PCOS progression remains
      largely unknown. Here, combining the DNA methylation profiling together with
      transcriptome analysis, we showed that (i) there were 7929 differentially
      methylated CpG sites (beta > 0.1, P < 0.05) and 650 differential transcripts
      (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes
      were identified with methylated levels that were correlated with gene
      transcription in PCOS; and (iii) there were less hypermethylated sites, but many
      more hypomethylated sites residing in CpG islands and N_Shore in PCOS. Among
      these genes, we identified that several significant pathways, including the type
      I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor
      signaling pathway, and some immune and inflammatory diseases may be highly
      involved in PCOS development. These results suggested that differences in genome
      wide DNA methylation and expression patterns exist between PCOS ovaries and
      normal ovaries; epigenetic mechanisms may in part be responsible for the
      different gene expression and PCOS phenotype. All of this may improve our
      understanding of the basic molecular mechanism underlying the development of
      PCOS. 

PMID- 25051373
TI  - KIAA1199 interacts with glycogen phosphorylase kinase beta-subunit (PHKB) to
      promote glycogen breakdown and cancer cell survival.
AB  - The KIAA1199 gene was first discovered to be associated with non-syndromic
      hearing loss. Recently, several reports have shown that the up-regulation of
      KIAA1199 is associated with cancer cell migration or invasion and a poor
      prognosis. These findings indicate that KIAA1199 may be a novel target for cancer
      therapy. Therefore, we explored in detail the function of KIAA1199 in cancer
      cells. In this study, we investigated the interaction of KIAA1199 protein with
      intracellular proteins in cancer cells. To this end, we expressed KIAA1199-MBP
      fusion protein and performed a pull-down assay. In addition, KIAA1199
      overexpressing cancer cell lines were constructed using a retroviral vector and
      were used for further experiments. A pull-down analysis showed that the glycogen
      phosphorylase kinase beta-subunit (PHKB) interacted with the C-terminal region of
      KIAA1199 protein. Furthermore, we observed the interaction of KIAA1199 with
      glycogen phosphorylase brain form (PYGB) under serum-free conditions. The
      interaction promoted glycogen breakdown and cancer cell survival. Our findings
      indicate that KIAA1199 plays an important role in glycogen breakdown and cancer
      cell survival and that it may represent a novel target for cancer therapy. 

PMID- 25051374
TI  - Mitophagy promotes replication of oncolytic Newcastle disease virus by blocking
      intrinsic apoptosis in lung cancer cells.
AB  - Apoptosis contributes to antitumor effect of Newcastle disease virus (NDV).
      Autophagy is a protective response under cellular stress including viral
      infection. How autophagy interferes with oncolysis of NDV remains unclear. In
      this study, we found that NDV La Sota strain induced autophagy and preserved
      autophagic flux in non-small cell lung cancer cells. NDV-induced autophagy
      promoted viral replication by blocking cancer cells from caspase-dependent
      apoptosis. Moreover, we found that NDV recruited SQSTM1-mediated mitophagy to
      control cytochrome c release, and thus blocked intrinsic pro-apoptotic signaling.
      Finally, we observed an enhanced oncolysis in NSCLC cells treated with NDV in the
      presence of an autophagy inhibitor 3-methyladenine (3-MA). Interestingly, a more
      profound antitumor effect could be achieved when administration of 3-MA was
      postponed to 24 h after NDV infection. Our findings unveil a novel way that NDV
      subverts mitophagy to favor its replication by blocking apoptosis, and provide
      rationale for systemic therapeutic cohort combining NDV with autophagy inhibitors
      in cancer therapy. 

PMID- 25051375
TI  - Novel celastrol derivatives inhibit the growth of hepatocellular carcinoma
      patient-derived xenografts.
AB  - The molecular co-chaperone CDC37 is over-expressed in hepatocellular carcinoma
      (HCC) cells, where it functions with HSP90 to regulate the activity of protein
      kinases in multiple oncogenic signaling pathways that contribute towards
      hepatocarcinogenesis. Disruption of these signaling pathways via inhibition of
      HSP90/CDC37 interaction is therefore a rational therapeutic approach. We
      evaluated the anti-tumor effects of celastrol, pristimerin, and two novel
      derivatives (cel-D2, and cel-D7) on HCC cell lines in vitro and on orthotopic HCC
      patient-derived xenografts in vivo. All four compounds preferentially inhibited
      viability of HCC cells in vitro,and significantly inhibited the growth of three
      orthotopic HCC patient-derived xenografts in vivo; with the novel derivatives cel
      D2 and cel-D7 exhibiting lower toxicity. All four compounds also induced cell
      apoptosis; and promoted degradation and inhibited phosphorylation of protein
      kinases in the Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways. We demonstrated
      that HSP90/CDC37 antagonists are potentially broad spectrum agents that might be
      beneficial for treating the heterogeneous subtypes of HCC, either as monotherapy,
      or in combination with other chemotherapeutic agents.

PMID- 25051378
TI  - Verification of wild-type EGFR status in non-small cell lung carcinomas using a
      mutant-enriched PCR on selected cases.
AB  - EGFR genotyping is required for targeted therapy of lung adenocarcinoma. Because
      a false-negative result might prevent a patient from receiving appropriate
      targeted therapies, it is desirable to recheck equivocal results of EGFR
      genotyping. A cohort of 346 lung cancers was tested with a commercial kit for
      EGFR mutations; nine of the cases had upward real-time amplification curves at
      late cycles. They were also investigated using mutant-enriched PCR with peptide
      nucleic acid-locked nucleic acid (PNA-sequencing). Six of the nine equivocal
      cases harbored EGFR mutations. These cases likely had a small amount of mutant
      DNA near the detection limit of the commercial kit. Twenty nonequivocal, wild
      type cases were reconfirmed using PNA-sequencing. We noticed a College of
      American Pathologists proficiency test material that showed a suspicious upward
      curve and eventually proved to have an H773_V774insPH in exon 20, for which a
      specific primer was not designed in the commercial kit. Further study using
      cloned DNA fragments showed that the upward curve most likely resulted from cross
      reaction between similar, but nonidentical, sequences. It is desirable to keep
      the number of false-negative results as low as possible, but rechecking all wild
      type cases is impractical. The late upward curves we observed helped identify
      suspicious cases for rechecking. A second method, such as PNA-sequencing, is
      recommended to verify wild-type cases.

PMID- 25051380
TI  - Time matters in 1: 1 resuscitations: concurrent administration of blood: plasma
      and risk of death.
AB  - BACKGROUND: The practice of 1:1 transfusion, administering packed red blood cells
      (PRBCs) with fresh frozen plasma (FFP), has been associated with improved
      survival. However, the reported ratios are the result of mathematical averages
      over 24 hours and do not necessarily represent concurrent administration. Using
      critical administration thresholds (CAT+) of more than 3 U of PRBC per hour to
      identify hemorrhaging patients, this study evaluates the effect of concurrent
      administration of PRBC/FFP on patient survival. METHODS: CAT+ patients identified
      retrospectively were eligible for analysis. The exact time of administration of
      each unit of PRBC and FFP was calculated. Each PRBC was matched to a
      corresponding unit of FFP given within 5 minutes before or after. Ideal 1:1
      ratios were calculated for each hour during the first day of admission. Hourly
      ratio groups were created (25%, 50%, 75% of transfusion opportunities) and
      evaluated as time-varying covariates. Cox proportional hazard ratio (HR) was used
      to determine risk of mortality, and Student's t test or Wilcoxon signed-rank test
      was used to compare groups. RESULTS: A total of 169 patients were initially
      identified (70% with New Injury Severity Score [NISS] > 10), 77 of whom were
      CAT+. There were no clinical differences between the groups in this study. In
      terms of mortality, patients who reached the 1:1 ratio 25% of the transfusion
      opportunities had an HR of 8.806 (95% confidence interval [CI], 1.845-42.034).
      Patients meeting the 1:1 ratio 50% of the opportunities had an HR of 5.062 (95%
      CI, 1.115-22.982) while those meeting 75% of the opportunities had an HR of 1.888
      (95% CI, 0.198-18.035). CONCLUSION: CAT+ patients represent the trauma subset at
      highest risk of mortality and may benefit from a focused blood-based
      resuscitation. Patients who were able to meet the 1:1 ratio more often had a
      noticeable decrease in risk of death compared with those who achieved less than
      1:1 transfusions. Administering FFP concurrently with PRBC is associated with a
      decrease in mortality in CAT+ patients. LEVEL OF EVIDENCE: Prognostic study,
      level III; therapeutic study, level IV.

PMID- 25051381
TI  - Attribution: whose complication is it?
AB  - BACKGROUND: To improve quality, programs such as accountable care organizations
      need to determine the part of the health care system most "responsible" for a
      complication. This is referred to as attribution. This provides a framework to
      compare physicians for patients and third-party payers. Traditionally, the
      attribution of complications has been to the admitting physician. This may
      misidentify the physician "responsible" for the complication. This is especially
      difficult in trauma patients who have multiple providers. We hypothesized that
      the current mechanism for attributing complications in trauma patients is
      inadequate and will need to be modernized. METHODS: All trauma admissions during
      a 12-month period were reviewed. Patients with single-system trauma were
      excluded. We reviewed our trauma database for mechanism of injury, complications,
      and readmissions. The trauma director and the medical director of our accountable
      care organizations reviewed all complications and attributed them to the
      appropriate health care provider. These were compared with the hospital decisions
      using the traditional definition. RESULTS: The trauma service had 1,526
      admissions. After exclusions, 1,019 patients were reviewed. One hundred twenty
      five complications occurred in 73 patients. Using the traditional definition, the
      acute care surgery service was assigned all 125 complications. Using the trauma
      director and medical director method, the neurosurgical attending accounted for
      36% (45 of 125) of complications. The acute care surgery attending was
      responsible for 34% (43 of 125) of complications, and orthopedic surgery was
      identified as the causative factor in 22% (27 of 125). The remaining 8% (10 of
      125) were attributed to various other services. Seven patients had unexpected
      readmissions. Most (6 of 7) of these were related to orthopedics. CONCLUSION:
      Hospital complications are now being assigned to individual surgeons. Which
      physician is responsible for each complication will be a controversial matter.
      Without a critical review process with physician input, up to two thirds of
      complications could be attributed incorrectly. The attribution process needs to
      be refined. LEVEL OF EVIDENCE: Epidemiologic study, level IV.

PMID- 25051379
TI  - The whole is greater than the sum of its parts: hemostatic profiles of whole
      blood variants.
AB  - BACKGROUND: Mounting evidence highlighting the benefits of hemostatic
      resuscitation has led to a renewed interest in whole blood (WB) and reconstituted
      WB (RWB). However, few data exist to characterize the clotting profiles of these
      variants. This study characterizes banked WB variants and RWB in standard 1:1:1
      and 2:1:1 transfusion ratios of packed red blood cells, fresh frozen plasma, and
      platelets (PLTs). We hypothesized that the global hemostatic profile of 1:1:1 RWB
      is superior to 2:1:1 RWB and that PLT-modified WB (MWB) is superior to 1:1:1 RWB.
      METHODS: Twenty-three units of packed red blood cells, fresh frozen plasma, and
      PLTs were obtained from the regional blood collection center and mixed to create
      23 1:1:1 and 23 2:1:1 RWB units. Freshly donated WB units were obtained and used
      to create 11 of each nonmodified WB (NMWB) (room temperature and cooled) and MWB
      (room temperature and cooled) variants. International normalized ratio
      (INR)/partial thromboplastin time (PTT), complete blood cell count, functional
      studies, and an extensive panel of procoagulant and anticoagulant factor assays
      were performed on all products. RESULTS: The 1:1:1 RWB had significantly lower
      INR and PTT (1.31 vs. 1.55, p = 0.0029; 42 seconds vs. 50 seconds, p = 0.0008)
      and higher activity of factors II, V, VII, VIII, IX, and X; antithrombin III, as
      well as protein C and higher fibrinogen levels than did 2:1:1 RWB (factor IX, 86%
      vs. 70%, p = 0.0313; fibrinogen, 242 mg/dL vs. 202 mg/dL, p = 0.0385). There were
      no differences in INR/PTT or factor activity between MWB and NMWB. However, MWB
      had greater maximum clot firmness (MCF) by rotational thromboelastometry tissue
      factor-activated extrinsic clotting cascade measures than did NMWB (MCF, 61 mm
      vs. 50 mm, p = 0.0031). MWB also had greater MCF by rotational thromboelastometry
      tissue factor-activated extrinsic clotting cascade measures than did 1:1:1 RWB
      (MCF, 61 mm vs. 45 mm, p = 0.0005). CONCLUSION: Although 1:1:1 RWB had a superior
      clotting profile relative to 2:1:1 RWB, MWB exhibited even better global
      hemostasis than did 1:1:1 RWB. Characterization of factor-level and functional
      clotting differences between WB variants is imperative for understanding the
      clinical benefits of hemostatic resuscitation.

PMID- 25051376
TI  - Circulating miR-148b and miR-133a as biomarkers for breast cancer detection.
AB  - Circulating microRNAs have drawn a great deal of attention as promising novel
      biomarkers for breast cancer. However, to date, the results are mixed. Here, we
      performed a three-stage microRNA analysis using plasma samples from breast cancer
      patients and healthy controls, with efforts taken to address several pitfalls in
      detection techniques and study design observed in previous studies. In the
      discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs
      differentially expressed between breast cancer cases and healthy controls. When
      those microRNAs were compared with published data from other studies, we
      identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose
      plasma levels were significantly higher in breast cancer cases than healthy
      controls and were also significant in previous independent studies. In the
      validation phase with 50 breast cancer cases and 50 healthy controls, we
      validated the associations with breast cancer detection for miR-148b and miR-133a
      (P = 1.5*10-6 and 1.3*10-10, respectively). In the in-vitro study phase, we found
      that both miR-148b and miR-133a were secreted from breast cancer cell lines,
      showing their secretory potential and possible tumor origin. Thus, our data
      suggest that both miR-148b and miR-133a have potential use as biomarkers for
      breast cancer detection.

PMID- 25051382
TI  - Melatonin inhibits thermal injury-induced hyperpermeability in microvascular
      endothelial cells.
AB  - BACKGROUND: Burns induce systemic inflammatory reactions and vascular
      hyperpermeability. Breakdown of endothelial cell adherens junctions is integral
      in this process, and reactive oxygen species (ROS) and proteolytic enzymes such
      as matrix metalloproteinase-9 (MMP-9) play pivotal roles therein. Outside trauma,
      melatonin has shown to exhibit anti-MMP activity and to be a powerful
      antioxidant. Consequently, we hypothesized that burn-induced junctional damage
      and hyperpermeability could be attenuated with melatonin. METHODS: Sprague-Dawley
      rats were assigned to sham or burn groups. Fluorescein isothiocyanate-bovine
      albumin was administered intravenously. Venules were examined with intravital
      microscopy; fluorescence intensities were measured intravascularly and
      extravascularly. Serum was collected. Rat lung microvascular endothelial cells
      were grown as monolayers and divided into four groups: sham serum and burn serum
      with and without melatonin pretreatment. Fluorescein isothiocyanate-bovine
      albumin flux was measured. Immunofluorescence for adherens junction proteins and
      staining for actin were performed, and images were captured. Cells were grown on
      96 well plates, and ROS species generation following application of burn and sham
      serum was analyzed with and without melatonin. Statistical analysis was conducted
      with the Student's t test. RESULTS: Intravital microscopy data revealed an
      increase in vascular hyperpermeability following burn (p < 0.05). Monolayer
      permeability was increased with burn serum (p < 0.05); this was attenuated with
      melatonin (p < 0.05). Immunofluorescence showed damage of rat lung microvascular
      endothelial cell adherens junctions with burn serum exposure, and melatonin
      restored integrity. Rhodamine phalloidin staining showed filamentous actin stress
      fiber formation after burn serum application, and melatonin decreased this. Burn
      serum significantly increased ROS species generation (p < 0.05), and melatonin
      negated this (p < 0.05). CONCLUSION: Burns damage endothelial adherens junctions
      and induce microvascular hyperpermeability; melatonin attenuates this process.
      This insight into the mechanisms of burn-induced fluid leak suggests the role of
      ROS and MMP-9 but more importantly hints at the possibility of new treatments to
      combat vascular hyperpermeability in burns.

PMID- 25051383
TI  - Effect of pharmacologic resuscitation on the brain gene expression profiles in a
      swine model of traumatic brain injury and hemorrhage.
AB  - BACKGROUND: We have previously shown that addition of valproic acid (VPA; a
      histone deacetylase inhibitor) to hetastarch (Hextend [HEX]) resuscitation
      significantly decreases lesion size in a swine model of traumatic brain injury
      (TBI) and hemorrhagic shock (HS). However, the precise mechanisms have not been
      well defined. As VPA is a transcriptional modulator, the aim of this study was to
      investigate its effect on brain gene expression profiles. METHODS: Swine were
      subjected to controlled TBI and HS (40% blood volume), kept in shock for 2 hours,
      and resuscitated with HEX or HEX + VPA (n = 5 per group). Following 6 hours of
      observation, brain RNA was isolated, and gene expression profiles were measured
      using a Porcine Gene ST 1.1 microarray (Affymetrix, Santa Clara, CA). Pathway
      analysis was done using network analysis tools Gene Ontology, Ingenuity Pathway
      Analysis, and Parametric Gene Set Enrichment Analysis. Real-time polymerase chain
      reaction was used to verify the key microarray findings. RESULTS: A total of
      1,668 probe sets mapping to 370 known genes were differentially expressed between
      the HEX and HEX + VPA groups. Expression of apoptotic genes differed between
      groups, and biologic function analysis predicted a significant downregulation of
      apoptosis (p = 1.29 * 10), cell death (p = 8.46 * 10), and necrosis (p = 9.07 *
      10). Pathway analysis indicated a significant modulation of pathways involved in
      cell signaling, dendritic cell response, and the complement system. CONCLUSION:
      This is the first high-throughput analysis of cerebral gene profiling following
      TBI + HS. It shows that treatment with VPA significantly alters early
      transcription of pathways related to cell survival, which may explain its
      neuroprotective effects.

PMID- 25051384
TI  - Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the
      spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy.
AB  - BACKGROUND: Fibrinolysis is a physiologic process maintaining patency of the
      microvasculature. Maladaptive overactivation of this essential function
      (hyperfibrinolysis) is proposed as a pathologic mechanism of trauma-induced
      coagulopathy. Conversely, the shutdown of fibrinolysis has also been observed as
      a pathologic phenomenon. We hypothesize that there is a level of fibrinolysis
      between these two extremes that have a survival benefit for the severely injured
      patients. METHODS: Thrombelastography and clinical data were prospectively
      collected on trauma patients admitted to our Level I trauma center from 2010 to
      2013. Patients with an Injury Severity Score (ISS) of 15 or greater were
      evaluated. The percentage of fibrinolysis at 30 minutes by thrombelastography was
      used to stratify three groups as follows: hyperfibrinolysis (>=3%), physiologic
      (0.081-2.9%), and shutdown (0-0.08%). The threshold for hyperfibrinolysis was
      based on existing literature. The remaining groups were established on a cutoff
      of 0.8%, determined by the highest point of specificity and sensitivity for
      mortality on a receiver operating characteristic curve. RESULTS: One hundred
      eighty patients were included in the study. The median age was 42 years
      (interquartile range [IQR], 28-55 years), 70% were male, and 21% had penetrating
      injuries. The median ISS was 29 (IQR, 22-36), and the median base deficit was 9
      mEq/L (IQR, 6-13 mEq/L). Distribution of fibrinolysis was as follows: shutdown,
      64% (115 of 180); physiologic, 18% (32 of 180); and hyperfibrinolysis, 18% (33 of
      180). Mortality rates were lower for the physiologic group (3%) compared with the
      hyperfibrinolysis (44%) and shutdown (17%) groups (p = 0.001). CONCLUSION: We
      have identified a U-shaped distribution of death related to the fibrinolysis
      system in response to major trauma, with a nadir in mortality, with level of
      fibrinolysis after 30 minutes between 0.81% and 2.9%. Exogenous inhibition of the
      fibrinolysis system in severely injured patients requires careful selection, as
      it may have an adverse affect on survival. LEVEL OF EVIDENCE: Prognostic study,
      level III.

PMID- 25051385
TI  - Histone deacetylase III as a potential therapeutic target for the treatment of
      lethal sepsis.
AB  - BACKGROUND: We have recently demonstrated that inhibition of histone deacetylase
      (HDAC) Class I, II, and IV with nonspecific HDAC inhibitors improves survival in
      a mouse model of lethal cecal ligation and puncture (CLP). However, the
      consequence of HDAC Class III inhibition is unknown in this model. The aims of
      the present study were to explore the effect of EX-527, a selective Sirtuin 1
      (SIRT1) inhibitor, on survival in the lethal model of CLP-sepsis and to assess
      the impact of the treatment on inflammatory cytokine production, coagulopathy,
      and bone marrow atrophy during severe sepsis. METHODS: For Experiment I, C57BL/6J
      mice were subjected to CLP and, 1 hour later, intraperitoneally injected with
      either EX-527 dissolved in dimethyl sulfoxide (DMSO) or DMSO only. Survival was
      monitored for 10 days. For Experiment II, 1 hour after CLP animals were randomly
      treated with (1) DMSO vehicle and (2) EX-527. Peritoneal fluid and blood samples
      were collected for measurement of cytokines, and blood was also used to evaluate
      coagulation status using thrombelastography. In addition, long bones (femurs and
      tibias) were examined to determine morphologic changes in the marrow by
      hematoxylin and eosin staining. For Experiment III, normal primary splenocytes
      were cultured and treated with lipopolysaccharide in the presence or absence of
      EX-527 to assess cytokine production. RESULTS: EX-527 significantly improved
      survival (50% vs. 0% survival as compared to vehicle, p = 0.0007) and attenuated
      levels of cytokines tumor necrosis factor alpha and interleukin 6 in the blood
      and the peritoneal fluid compared with the vehicle control. It also decreased
      tumor necrosis factor alpha and interleukin 6 production by splenocytes in vitro.
      Selective inhibition of SIRT1 was associated with significant improvements in
      fibrin cross-linkage, platelet function, and clot rigidity but had no significant
      impact on the clot initiation parameters. Moreover, inhibition of SIRT1 was
      associated with a significant decrease in bone marrow atrophy. CONCLUSION:
      Selective inhibition of Class III HDAC SIRT1 significantly improves survival,
      attenuates cytokine levels and sepsis-associated coagulopathy, and decreases bone
      marrow atrophy in a lethal mouse septic model.

PMID- 25051387
TI  - "Magnitude-based inference": a statistical review.
AB  - PURPOSE: We consider "magnitude-based inference" and its interpretation by
      examining in detail its use in the problem of comparing two means. METHODS: We
      extract from the spreadsheets, which are provided to users of the analysis
      (http://www.sportsci.org/), a precise description of how "magnitude-based
      inference" is implemented. We compare the implemented version of the method with
      general descriptions of it and interpret the method in familiar statistical
      terms. RESULTS AND CONCLUSIONS: We show that "magnitude-based inference" is not a
      progressive improvement on modern statistics. The additional probabilities
      introduced are not directly related to the confidence interval but, rather, are
      interpretable either as P values for two different nonstandard tests (for
      different null hypotheses) or as approximate Bayesian calculations, which also
      lead to a type of test. We also discuss sample size calculations associated with
      "magnitude-based inference" and show that the substantial reduction in sample
      sizes claimed for the method (30% of the sample size obtained from standard
      frequentist calculations) is not justifiable so the sample size calculations
      should not be used. Rather than using "magnitude-based inference," a better
      solution is to be realistic about the limitations of the data and use either
      confidence intervals or a fully Bayesian analysis.

PMID- 25051386
TI  - Characteristics of surgical patients receiving inappropriate empiric
      antimicrobial therapy.
AB  - BACKGROUND: Inappropriate antibiotics have been observed to result in an
      increased duration of antibiotic treatment and hospital length of stay,
      development of multidrug-resistant organisms, and mortality rate compared with
      appropriate antibiotic treatment. Few studies have evaluated independent risk
      factors associated with inappropriateness. The purpose of this study was to
      identify independent predictors of inappropriate, empiric antimicrobial therapy
      for the treatment of severe sepsis. METHODS: This was a retrospective analysis of
      a prospectively maintained database of all surgical/trauma patients admitted to a
      tertiary care center from 1996 to 2007 and treated for sepsis. "Appropriate"
      empiric antibiotic treatment was determined by sensitivity testing. Demographics
      and comorbidities, infection sites, infection organisms, and outcomes between
      strata were compared. Differences in outcome were estimated using relative risk
      and 95% confidence intervals for correlated data. RESULTS: A total of 2,855
      patients (7,158 infections) were identified. Independent predictors of
      inappropriate, empiric antimicrobial therapy for the treatment of severe sepsis
      included site of infection and organism type. Severity of illness, age, medical
      conditions, and community versus health care-associated infections were not
      associated with inappropriate therapy. Although inappropriate empiric therapy was
      associated with a longer length of stay and duration of antimicrobial use, it did
      not result in higher mortality. CONCLUSION: Our study observed that inappropriate
      empiric antibiotic selection is related to site of infection and pathogen. Other
      clinical variables do not appear to predict inappropriateness of antibiotic
      treatment. Efforts should be focused on early broad-spectrum therapy and more
      rapid microbiologic methods. LEVEL OF EVIDENCE: Therapeutic/care management
      study, level II.

PMID- 25051388
TI  - Central and peripheral fatigue in male cyclists after 4-, 20-, and 40-km time
      trials.
AB  - PURPOSE: Few studies have assessed neuromuscular fatigue after self-paced
      locomotor exercise; moreover, none have assessed the degree of supraspinal
      fatigue. This study assessed central and peripheral fatigue after self-paced
      exercise of different durations. METHODS: Thirteen well-trained male cyclists
      completed 4-, 20-, and 40-km simulated time trials (TTs). Pre- and immediately
      post-TT (<2.5 min), twitch responses from the knee extensors to electrical
      stimulation of the femoral nerve and transcranial magnetic stimulation of the
      motor cortex were recorded to assess neuromuscular and corticospinal function.
      RESULTS: Time to complete 4-, 20-, and 40-km TTs was 6.0 +/- 0.2, 31.8 +/- 1.0,
      and 65.8 +/- 2.2 min at average exercise intensities of 96%, 92%, and 87% of
      maximum oxygen uptake, respectively. Exercise resulted in significant reductions
      in maximum voluntary contraction, with no difference between TTs (-18%, -15%, and
      -16% for 4-, 20-, and 40-km TTs, respectively). Greater peripheral fatigue was
      evident after 4-km (40% reduction in potentiated twitch) compared with that after
      20-km (31%) and 40-km TTs (29%). In contrast, longer TTs were characterized by
      more central fatigue, with greater reductions in voluntary activation measured by
      motor nerve (-11% and -10% for 20- and 40-km TTs vs -7% for 4-km TTs) and
      cortical stimulation (-12% and -10% for 20- and 40-km vs -6% for 4-km).
      CONCLUSIONS: These data demonstrate that fatigue after self-paced exercise is
      task dependent, with a greater degree of peripheral fatigue after shorter higher
      intensity (6 min) TTs and more central fatigue after longer lower-intensity TTs
      (>30 min).

PMID- 25051389
TI  - Physical activity and skills intervention: SCORES cluster randomized controlled
      trial.
AB  - PURPOSE: Physical activity (PA) declines dramatically during adolescence, and
      activity levels are consistently lower among children living in low-income
      communities. Competency in a range of fundamental movement skills (FMS) may serve
      as a protective factor against the decline in PA typically observed during
      adolescence. The purpose of this study was to evaluate the effect of a 12-month
      multicomponent PA and FMS intervention on children attending primary schools in
      low-income communities. METHODS: The Supporting Children's Outcomes using
      Rewards, Exercise, and Skills intervention was evaluated using a cluster
      randomized controlled trial. The sample included 25 classes from eight primary
      schools located in low-income communities. Participants were 460 children (54.1%
      girls) age 8.5 +/- 0.6 yr. Primary outcomes were objectively measured PA
      (ActiGraph GT3X and GT3X+ accelerometers), FMS competency (Test of Gross Motor
      Development 2, six locomotor and six object control skills), and
      cardiorespiratory fitness (20-m multistage fitness test) assessed at baseline,
      midprogram (6-months), and at posttest (12 months). Linear mixed models, adjusted
      for sex, age, body mass index z-score, socioeconomic status, ethnicity, and
      school class as a random factor, were used to assess the effect of the
      intervention. RESULTS: At midprogram, there were no significant intervention
      effects for any of the outcomes. At posttest (study's primary time point), there
      were intervention effects for daily moderate-to-vigorous PA (MVPA) (adjusted mean
      difference, 12.7 min.d of MVPA; 95% confidence interval (CI), 5.0-20.5), overall
      FMS competency (4.9 units; 95% CI, -0.04 to 9.8), and cardiorespiratory fitness
      (5.4 laps; 95% CI, 2.3-8.6). CONCLUSIONS: A school-based multicomponent PA and
      FMS intervention maintained daily MVPA, improved overall FMS competency, and
      increased cardiorespiratory fitness among children attending primary schools in
      low-income communities.

PMID- 25051390
TI  - Caffeinated energy drinks improve volleyball performance in elite female players.
AB  - PURPOSE: The objective of this study is to determine the effects of a caffeine
      containing energy drink on female volleyball players' performance. METHODS:
      Thirteen elite female volleyball players ingested 3 mg.kg of caffeine with an
      energy drink or the same drink without caffeine (placebo drink) in a double-blind
      and randomized study. Then, participants performed the following: standing spike,
      jumping spike, spike jump, blocking jump, squat jump, countermovement jump,
      manual dynamometry, and the agility t-test. A simulated volleyball game was
      played, videotaped, and notated afterward. RESULTS: In comparison to the placebo
      drink, the ingestion of the caffeinated energy drink increased the ball velocity
      in the standing spike (19.2 +/- 2.1 vs 19.7 +/- 1.9 m.s, P = 0.023) and in the
      jumping spike (17.9 +/- 2.2 vs 18.8 +/- 2.2 m.s, P = 0.038) and the jump height
      in the squat jump (28.1 +/- 3.2 vs 29.4 +/- 3.6 cm, P = 0.028), countermovement
      jump (32.0 +/- 4.6 vs 33.1 +/- 4.5 cm, P = 0.018), spike jump (43.3 +/- 4.7 vs
      44.4 +/- 5.0 cm, P = 0.025), and block jump (35.2 +/- 5.1 vs 36.1 +/- 5.1 cm, P =
      0.044). Furthermore, the caffeinated energy drink decreased the time needed to
      complete the agility t-test (11.1 +/- 0.5 vs 10.9 +/- 0.3 s, P = 0.036). During
      the game, the volleyball actions categorized as successful were more frequent
      with the caffeinated energy drink (34% +/- 9% vs 45% +/- 9%, P < 0.001), whereas
      imprecise actions decreased (28% +/- 7% vs 14% +/- 9%, P < 0.001) when compared
      with the placebo drink. CONCLUSION: Commercially available energy drinks can
      significantly improve physical performance in female volleyball players.
      Increased physical performance led to improved accuracy during an actual
      volleyball match.

PMID- 25051391
TI  - Measurement of exciton diffusion in a well-defined donor/acceptor heterojunction
      based on a conjugated polymer and cross-linked fullerene derivative.
AB  - We designed a well-defined donor/acceptor heterojunction for measuring exciton
      diffusion lengths in conjugated polymers. To obtain an insoluble electron
      acceptor layer, a new cross-linkable fullerene derivative (bis-PCBVB) was
      synthesized by functionalizing [6,6]-diphenyl-C62-bis(butyric acid methyl ester)
      (bis-PCBM) with two styryl groups. The spin-coated bis-PCBVB film was cross
      linked in situ by heating at 170  degrees C for 60 min. Surface characterizations
      by UV-visible absorption, atomic force microscopy, and photoelectron yield
      spectroscopy revealed that a smooth and solvent-resistant film (p-PCBVB) was
      obtained. In bilayer films with a donor conjugated polymer, poly[2,7-(9,9
      didodecylfluorene)-alt-5,5-(4',7'-bis(2-thienyl)-2',1',3'-benzothiadiazole)]
      (PF12TBT), spin-coated on top of the p-PCBVB acceptor layer, the
      photoluminescence (PL) of the PF12TBT was effectively quenched. This is because
      the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular
      orbital (LUMO) energy levels of the p-PCBVB film are nearly the same as those of
      the parent bis-PCBM spin-coated film. On the basis of the PL quenching results,
      the exciton diffusion length and exciton diffusion coefficient in the PF12TBT
      were evaluated to be 11 nm and 9.8 * 10(-4) cm(2) s(-1), respectively. 

PMID- 25051392
TI  - Synergistic activity of Bacillus thuringiensis toxins against Simulium spp.
      larvae.
AB  - Species of Simulium spread diseases in humans and animals such as onchocerciasis
      and mansonelosis, causing health problems and economic loses. One alternative for
      controlling these insects is the use of Bacillus thuringiensis serovar
      israelensis (Bti). This bacterium produces different dipteran-active Cry and Cyt
      toxins and has been widely used in blackfly biological control programs
      worldwide. Studies on other insect targets have revealed the role of individual
      Cry and Cyt proteins in toxicity and demonstrated a synergistic effect among
      them. However, the insecticidal activity and interactions of these proteins
      against Simulium larvae have not been reported. In this study we demonstrate that
      Cry4Ba is the most effective toxin followed by Cry4Aa and Cry11Aa. Cry10Aa and
      Cyt1Aa were not toxic when administered alone but both were able to synergise the
      activity of Cry4B and Cry11Aa toxins. Cyt1Aa is also able to synergise with
      Cry4Aa. The mixture of all toxin-producing strains showed the greatest level of
      synergism, but still lower than the Bti parental strain. 

PMID- 25051393
TI  - Luteolin decreases the attachment, invasion and cytotoxicity of UPEC in bladder
      epithelial cells and inhibits UPEC biofilm formation.
AB  - Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli
      (UPEC), is one of the most common infectious diseases worldwide. Emerging
      antibiotic resistance requires novel treatment strategies. Luteolin, a dietary
      polyphenolic flavonoid, has been confirmed as a potential antimicrobial agent.
      Here, we evaluated the sub-MICs of luteolin for potential properties to modulate
      the UPEC infection. We found that luteolin significantly decreased the attachment
      and invasion of UPEC J96 or CFT073 in human bladder epithelial cell lines T24.
      Meanwhile, obvious decreased expression of type 1 fimbriae adhesin fimH gene,
      lower bacterial surface hydrophobicity and swimming motility, were observed in
      luteolin-pretreated UPEC. Furthermore, luteolin could attenuate UPEC-induced
      cytotoxicity in T24 cells, which manifested as decreased activity of lactate
      dehydrogenase (LDH). Simultaneously, the inhibition of luteolin on UPEC-induced
      cytotoxicity was confirmed by ethidium bromide/acridine orange staining. Finally,
      the luteolin-pretreated UPEC showed a lower ability of biofilm formation.
      Collectively, these results indicated that luteolin decreased the attachment and
      invasion of UPEC in bladder epithelial cells, attenuated UPEC-induced
      cytotoxicity and biofilm formation via down-regulating the expression of adhesin
      fimH gene, reducing the bacterial surface hydrophobicity and motility. 

PMID- 25051394
TI  - Protective effect of polydatin, a natural precursor of resveratrol, against
      cisplatin-induced toxicity in rats.
AB  - The aim of the present study was to evaluate the possible protective effect of
      polydatin (PD) on cisplatin (Cis) induced oxidative stress in rats. Totally,
      thirty male Wistar albino rats were fed standard rodent diet and divided into 5
      equal groups: the control group (vehicle treated) was treated with physiological
      saline for ten days both orally and intraperitoneally (i.p.), the second group
      was orally treated with physiological saline and 7 mg/kg single i.p. injection of
      Cis on the seventh day, and third, fourth, and fifth groups were treated orally
      PD at 25, 50, and 100 mg/kg/day, respectively for 10 days starting seven days
      before Cis injection and 7 mg/kg single i.p. Cis was injected on the seventh day.
      Cis resulted in significant increase malondialdehyde levels and decreased
      glutathione levels. In addition, Cis treatment decreased superoxide dismutase and
      catalase activities in erythrocyte and tissues. Also, Cis treatment caused to
      increase DNA damage and affected serum biochemical parameters whereas slightly
      decreased AchE activity. However, treatment of PD resulted in reversal of Cis
      induced oxidative stress, lipid peroxidation, and activities of antioxidant
      enzymes. In conclusion, PD has protective effect in rats against Cis-induced
      oxidative stress, enhances antioxidant defence mechanism, and regenerates their
      tissues.

PMID- 25051395
TI  - Mesoscopic features of charge generation in organic semiconductors.
AB  - CONSPECTUS: In the past two decades, organic materials have been extensively
      investigated by numerous research groups worldwide for implementation in organic
      photovoltaic (OPV) devices. The interest in organic semiconductors is spurred by
      their potential low cost and facile tunability, making OPV devices a potentially
      disruptive technology. To study OPV operating mechanisms is also to explore a
      knowledge gap in our general understanding of materials, because both the time
      scales (femtosecond to microsecond) and length scales (nanometer to micrometer)
      relevant to OPV functionality occupy a challenging and fascinating space between
      the traditional regimes of quantum chemistry and solid-state physics. New
      theoretical frameworks and computational tools are needed to bridge the
      aforementioned length and time scales, and they must satisfy the criteria of
      computational tractability for systems involving 10(4)-10(6) atoms, while also
      maintaining predictive utility. While this challenge is far from solved, advances
      in density functional theory (DFT) have allowed researchers to investigate the
      ground- and excited-state properties of many intermediate sized systems (10(2)
      10(3) atoms) that provide the outlines of the larger problem. Results on these
      smaller systems are already sufficient to predict optical gaps and trends in
      valence band energies, correct erroneous interpretations of experimental data,
      and develop models for charge generation and transport in OPV devices. The active
      films of high-efficiency OPV devices are comprised of mesoscopic mixtures of
      electron donor (D) and electron acceptor (A) species, a "bulk-heterojunction"
      (BHJ) device, subject to variable degrees of structural disorder. Depending on
      the degree of intermolecular electronic coupling and energy level alignment, the
      spatial delocalization of photoexcitations and charge carriers can affect the
      dynamics of the solar cell. In this Account, we provide an overview of three
      pivotal characteristics of solar cells that possess strong delocalization
      dependence: (1) the exciton binding energy, (2) charge transfer at the D-A
      heterojunction, and (3) the energy landscape in the vicinity of the D-A
      heterojunction. In each case, the length scale dependence can be assessed through
      DFT calculations on reference systems, with a view to establishing general
      trends. Throughout the discussion, we draw from the experimental and theoretical
      literature to provide a consistent view of what is known about these properties
      in actual BHJ blends. A consistent interpretation of the results to date affords
      the following view: transient delocalization effects and resonant charge transfer
      at the heterojunction are capable of funneling excitations away from trap states
      and mediating exciton dissociation; these factors alone are capable of explaining
      the remarkably good charge generation currently achieved in OPV devices. The
      exciton binding energy likely plays a minimal role in modern OPV devices, since
      the presence of the heterojunction serves to bypass the costly exciton-to-free
      charge transition state.

PMID- 25051396
TI  - The strong specific effect of coions on micellar growth from molecular
      thermodynamic theory.
AB  - Viscoelastic solutions of ionic surfactants with an added salt exhibit a
      surprisingly strong dependence of their behavior on the nature of the added
      coion. We apply a recently proposed molecular-thermodynamic model to elucidate
      the effect of a coion's specificity on the aggregation of cationic and anionic
      surfactants. We show that micellar growth and branching are opposed by
      penetration of coions inside a micelle's corona leading to an increase of the
      aggregate's preferential curvature. These effects result from
      hydration/dehydration and dispersion attraction of coions and are only important
      at high salinity where electrostatic repulsion of coions from the micelle is
      screened and where branching of micelles and viscosity maxima are observed. At
      low and medium salinity, the coion plays a minor role; its effect on critical
      micelle concentration and sphere-to-rod transitions is insignificant. Our
      molecular-thermodynamic approach describes the specific effects of both
      counterions and coions and their different roles at different salinity levels
      based on a unified physical picture. 

PMID- 25051398
TI  - Effects of lentivirus-mediated RNAi knockdown of NEDD9 on human lung
      adenocarcinoma cells in vitro and in vivo.
AB  - The aim of the present study was to investigate the biological behavior of lung
      adenocarcinoma A549 cells following transfection with NEDD9-specific lentiviral
      particles in vitro and in vivo. NEDD9-specific lentiviral particles were
      chemically synthesized and transfected into the human lung adenocarcinoma A549
      cell line. NEDD9 mRNA and protein levels were determined by fluorescence
      quantitative RT-PCR and western blotting. Cell proliferation was evaluated using
      soft agar colony formation assays and flow cytometric analysis. Migration and
      invasion were evaluated by wound-healing and transwell assays and xenograft
      animal models. Transfection was successful, and expression levels of NEDD9 mRNA
      and protein in the lentivirus-NEDD9-siRNA group were downregulated. As indicated
      by soft agar colony formation assays, the number of clones in the siRNA group
      were significantly lower than the number of colonies in the blank and negative
      control groups (P<0.01). In addition, the percentage of cells in the S phase in
      the siRNA group was significantly lower than the percentages in the blank and
      negative control groups (P<0.05). Furthermore, as detected by cell migration and
      invasion assays, values of wound healing were increased and the number of
      invading cells were decreased in the siRNA group (both P<0.05). We also showed
      that lentivirus-mediated NEDD9-siRNA decreased the growth potential of
      subcutaneous A549 xenografts in vivo. These data imply that knockdown of the
      NEDD9 gene results in suppression of tumor cell proliferation, migration,
      invasion and cell growth in vitro and in vivo. Lentivirus-mediated NEDD9-siRNA
      may have potential therapeutic utility for human lung adenocarcinoma. 

PMID- 25051397
TI  - Effect of ginsenoside Rh2 on the migratory ability of HepG2 liver carcinoma
      cells: recruiting histone deacetylase and inhibiting activator protein 1
      transcription factors.
AB  - In previous experiments, ginsenoside Rh2 induced apoptosis and cell cycle arrest,
      which indicates a potential role for ginsenoside Rh2 in anticancer treatment. The
      effect of ginsenoside Rh2 on cancer is marked and ginsenoside Rh2 has been shown
      to inhibit pancreatic tumor migratory ability. In the present study, Transwell
      chambers were used in order to investigate whether ginsenoside Rh2 inhibits the
      migratory ability of HepG2 liver carcinoma cells. Furthermore, to analyze
      activator protein 1 (AP-1) transcription factor expression following Rh2
      treatment, ten plasmids encoding Renilla luciferase coupled to the transcription
      factors were transiently transfected into the HepG2 cells and luciferase was
      detected by the Luciferase Reporter Assay system reagent. The results indicated
      that ginsenoside Rh2 inhibited HepG2 cell migratory ability. The expression
      levels of AP-1 transcription factors were increased in HepG2 cells following
      induction by phorbol 12-myristate 13-acetate, but ginsenoside Rh2 suppressed this
      induced AP-1 expression. AP-1 transcription factors recruit histone deacetylase
      (HDAC)4 and affect its transcription, thus, the expression levels of HDAC4 were
      also analyzed, and these were found to be increased in the Rh2 treatment group.
      Matrix metalloproteinase 3 (MMP3), a gene downstream of AP-1, was then
      investigated, and the treatment group expressed reduced levels of MMP3 gene and
      protein. Therefore, the inhibitory effect of ginsenoside Rh2 on the migratory
      ability of HepG2 may be presumed to occur by the recruitment of HDAC and the
      resulting inhibition of AP-1 transcription factors, in order to reduce the
      expression levels of MMP3 gene and protein.

PMID- 25051400
TI  - Meibomian gland dropout in patients with dry eye disease in China.
AB  - PURPOSE: To examine the morphological changes in the meibomian glands of eyes of
      patients with dry eye disease using the non-contact infrared meibography system
      and to assess their relationship with meibomian dropout, signs, and tear-film
      function. METHODS: Subjects included 264 randomly selected patients (528 eyes)
      suffering from dry eye disease (95 males, 169 females; age range, 7-85 years;
      mean male age, 39.83 +/- 19.17 years; mean female age, 46.16 +/- 17.38 years).
      Tear-film break-up time (BUT) was measured and tear-film production was evaluated
      by the Schirmer test I (SIT). Subjective symptoms were also scored. The upper and
      lower eyelids were turned over, and the meibomian glands were observed using the
      non-contact meibography system. Partial or complete loss of the meibomian glands
      (meibomian dropout) was scored for each eyelid from grade 0 (no loss) through
      grade 3 (lost area was >2/3 of the total meibomian gland area). RESULTS: The
      average SIT result was 6.71 +/- 6.13 mm (range 0-30 mm) and that for BUT was 3.13
      +/- 2.39 s (range 0-10 s). The average fluorescein staining score was 4.25 +/-
      4.05 (range 0-12). In addition, the mean meibomian gland photographic score was
      4.35 +/- 1.39. The correlation between the meibomian gland photographic scores
      and various ocular surface examinations were evaluated using Kendall's
      correlation. SIT and BUT were significantly negatively correlated with the
      meibomian gland photographic score, whereas corneal fluorescein staining was
      positively correlated. CONCLUSIONS: The results suggest a large proportion of
      meibomian dropout cases among patients with dry eye disease, indicating that
      treatment targeted at the meibomian gland will become an important direction for
      treating dry eye disease. Meibography is recommended as a routine test for dry
      eye disease.

PMID- 25051401
TI  - Autonomous in situ measurements of seawater alkalinity.
AB  - Total alkalinity (AT) is an important parameter for describing the marine
      inorganic carbon system and understanding the effects of atmospheric CO2 on the
      oceans. Measurements of AT are limited, however, because of the laborious process
      of collecting and analyzing samples. In this work we evaluate the performance of
      an autonomous instrument for high temporal resolution measurements of seawater
      AT. The Submersible Autonomous Moored Instrument for alkalinity (SAMI-alk) uses a
      novel tracer monitored titration method where a colorimetric pH indicator
      quantifies both pH and relative volumes of sample and titrant, circumventing the
      need for gravimetric or volumetric measurements. The SAMI-alk performance was
      validated in the laboratory and in situ during two field studies. Overall in situ
      accuracy was -2.2 +/- 13.1 MUmol kg(-1) (n = 86), on the basis of comparison to
      discrete samples. Precision on duplicate analyses of a carbonate standard was +/
      4.7 MUmol kg(-1) (n = 22). This prototype instrument can measure in situ AT
      hourly for one month, limited by consumption of reagent and standard solutions. 

PMID- 25051402
TI  - Restricted natural language based querying of clinical databases.
AB  - PURPOSE: To elevate the level of care to the community it is essential to provide
      usable tools for healthcare professionals to extract knowledge from clinical
      data. In this paper a generic translation algorithm is proposed to translate a
      restricted natural language query (RNLQ) to a standard query language like SQL
      (Structured Query Language). METHODS: A special purpose clinical data analytics
      language (CliniDAL) has been introduced which provides scheme of six classes of
      clinical questioning templates. A translation algorithm is proposed to translate
      the RNLQ of users to SQL queries based on a similarity-based Top-k algorithm
      which is used in the mapping process of CliniDAL. Also a two layer rule-based
      method is used to interpret the temporal expressions of the query, based on the
      proposed temporal model. The mapping and translation algorithms are generic and
      thus able to work with clinical databases in three data design models, including
      Entity-Relationship (ER), Entity-Attribute-Value (EAV) and XML, however it is
      only implemented for ER and EAV design models in the current work. RESULTS: It is
      easy to compose a RNLQ via CliniDAL's interface in which query terms are
      automatically mapped to the underlying data models of a Clinical Information
      System (CIS) with an accuracy of more than 84% and the temporal expressions of
      the query comprising absolute times, relative times or relative events can be
      automatically mapped to time entities of the underlying CIS and to normalized
      temporal comparative values. CONCLUSION: The proposed solution of CliniDAL using
      the generic mapping and translation algorithms which is enhanced by a temporal
      analyzer component provides a simple mechanism for composing RNLQ for extracting
      knowledge from CISs with different data design models for analytics purposes.

PMID- 25051403
TI  - Modular design, application architecture, and usage of a self-service model for
      enterprise data delivery: the Duke Enterprise Data Unified Content Explorer
      (DEDUCE).
AB  - PURPOSE: Data generated in the care of patients are widely used to support
      clinical research and quality improvement, which has hastened the development of
      self-service query tools. User interface design for such tools, execution of
      query activity, and underlying application architecture have not been widely
      reported, and existing tools reflect a wide heterogeneity of methods and
      technical frameworks. We describe the design, application architecture, and use
      of a self-service model for enterprise data delivery within Duke Medicine.
      METHODS: Our query platform, the Duke Enterprise Data Unified Content Explorer
      (DEDUCE), supports enhanced data exploration, cohort identification, and data
      extraction from our enterprise data warehouse (EDW) using a series of modular
      environments that interact with a central keystone module, Cohort Manager (CM). A
      data-driven application architecture is implemented through three components: an
      application data dictionary, the concept of "smart dimensions", and dynamically
      generated user interfaces. RESULTS: DEDUCE CM allows flexible hierarchies of EDW
      queries within a grid-like workspace. A cohort "join" functionality allows
      switching between filters based on criteria occurring within or across patient
      encounters. To date, 674 users have been trained and activated in DEDUCE, and
      logon activity shows a steady increase, with variability between months. A
      comparison of filter conditions and export criteria shows that these activities
      have different patterns of usage across subject areas. CONCLUSIONS: Organizations
      with sophisticated EDWs may find that users benefit from development of advanced
      query functionality, complimentary to the user interfaces and infrastructure used
      in other well-published models. Driven by its EDW context, the DEDUCE application
      architecture was also designed to be responsive to source data and to allow
      modification through alterations in metadata rather than programming, allowing an
      agile response to source system changes.

PMID- 25051404
TI  - Chromatin structure, transcriptional activity and DNA repair efficiency affect
      the outcome of chemotherapy in multiple myeloma.
AB  - BACKGROUND: Melphalan is one of the most active chemotherapeutic agents in the
      treatment of multiple myeloma (MM). However, the mechanism underlying
      differential patient responses to melphalan therapy is unknown. METHODS:
      Chromatin structure, transcriptional activity and DNA damage response signals
      were examined following ex vivo treatment with melphalan of both malignant bone
      marrow plasma cells (BMPCs) and peripheral blood mononuclear cells (PBMCs) of MM
      patients, responders (n=57) or non-responders (n=28) to melphalan therapy. PBMCs
      from healthy controls (n=25) were also included in the study. RESULTS: In both
      BMPCs and PBMCs, the local chromatin looseness, transcriptional activity and
      repair efficiency of the transcribed strand (TS) were significantly higher in non
      responders than in responders and lowest in healthy controls (all P<0.05).
      Moreover, we found that melphalan-induced apoptosis inversely correlated with the
      repair efficiency of the TS, with the duration of the inhibition of mRNA
      synthesis, phosphorylation of p53 at serine 15 and apoptosis rates being higher
      in responders than in non-responders (all P<0.001). CONCLUSIONS: Our findings
      provide a mechanistic basis for the link between DNA repair efficiency and
      response to melphalan therapy. Interestingly, the observation of these phenomena
      in PBMCs provides a novel approach for the prediction of response to anti-myeloma
      therapy.

PMID- 25051405
TI  - The impact of plasma Epstein-Barr virus DNA and fibrinogen on nasopharyngeal
      carcinoma prognosis: an observational study.
AB  - BACKGROUND: The impact of combining plasma fibrinogen levels with Epstein-Barr
      Virus DNA (EBV DNA) levels on the prognosis for patients with nasopharyngeal
      carcinoma (NPC) was evaluated. METHODS: In this observational study, 2563
      patients with non-metastatic NPC were evaluated for the effects of circulating
      plasma fibrinogen and EBV DNA levels on disease-free survival (DFS), distant
      metastasis-free survival (DMFS), and overall survival (OS). RESULTS: Compared
      with the bottom biomarker tertiles, TNM stage-adjusted hazard ratios (HR, 95%
      confidence intervals (CIs)) for predicting DFS in fibrinogen tertiles 2 to 3 were
      1.26 (1.00 to 1.60) and 1.81 (1.45 to 2.26), respectively; HR for EBV DNA
      tertiles 2 to 3 were 1.49 (1.12 to 1.98) and 4.24 (3.27 to 5.49), respectively.
      After additional adjustment for established risk factors, both biomarkers were
      still associated (P for trend <0.001) with reduced DFS (HR: 1.79, 95% CI, 1.43 to
      2.25 for top fibrinogen tertiles; HR: 4.04, 95% CI: 3.10 to 5.27 for top EBV DNA
      tertiles compared with the bottom tertiles). For patients with advanced-stage
      disease, those with high fibrinogen levels (3.34 g l(-1)) presented with worse
      DFS, regardless of EBV DNA 4000 or <4000 copies ml(-1) subgroup. Similar findings
      were observed for DMFS and OS. CONCLUSIONS: Circulating fibrinogen and EBV DNA
      significantly correlate with NPC patients survival. Combined fibrinogen and EBV
      DNA data lead to improved prognostic prediction in advanced-stage disease.

PMID- 25051406
TI  - Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical
      reappraisal of its prognostic role.
AB  - BACKGROUND: Uncontrolled proliferation is a hallmark of malignant tumour growth.
      Its prognostic role in non-small cell lung cancer (NSCLC) has been investigated
      in numerous studies with controversial results. We aimed to resolve these
      controversies by assessing the Ki-67 proliferation index (PI) in three large,
      independent NSCLC cohorts. METHODS: Proliferation index was retrospectively
      analysed by immunohistochemistry in a cohort of 1065 NSCLC and correlated with
      clinicopathological data including outcome and therapy. RESULTS were validated in
      two independent cohorts of 233 squamous cell carcinomas (SQCC) and 184
      adenocarcinomas (ADC). RESULTS: Proliferation index (overall mean: 40.7%)
      differed significantly according to histologic subtypes with SQCC showing a mean
      PI (52.8%) twice as high as ADC (25.8%). In ADC PI was tightly linked to growth
      patterns. In SQCC and ADC opposing effects of PI on overall (OS), disease
      specific and disease-free survival were evident, in ADC high PI (optimised
      validated cut-off: 25%) was a stage-independent negative prognosticator (hazard
      ratio, HR OS: 1.56, P=0.004). This prognostic effect was largely attenuated by
      adjuvant radio-/chemotherapy. In SQCC high PI (optimised validated cut-off: 50%)
      was associated with better survival (HR OS: 0.65, P=0.007). CONCLUSIONS: Our data
      demonstrate that PI is a clinically meaningful biomarker in NSCLC with entity
      dependent cut-off values that allow reliable estimation of prognosis and may
      potentially stratify ADC patients for the need of adjuvant therapy.

PMID- 25051407
TI  - Redefining high-risk patients with stage II colon cancer by risk index and
      microRNA-21: results from a population-based cohort.
AB  - BACKGROUND: The aim of the present study was to analyse the prognostic value of
      microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk
      index for this group of patients. METHODS: A population-based cohort of 554
      patients was included. MicroRNA-21 was analysed by qPCR based on tumour tissue.
      An index was created using the coefficients obtained from a collective multiple
      Cox regression. The entire procedure was cross-validated (10-fold). The
      performance of the index was quantified by time-dependent receiver operating
      characteristics curves. RESULTS: High miRNA-21 expression was associated with an
      unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35
      (95% confidence interval, 1.03-1.76) (P=0.028). The generated RF-CSS index
      divided the traditional high-risk patients into subgroups with 5-year RF-CSS
      rates of 87% and 73%, respectively (P<0.001). The overall survival (OS) index
      identified three different subgroups (P<0.001). Cross-validated 5-year OS rates
      were 88%, 68%, and 50%, respectively. CONCLUSIONS: This population-based study
      supports miRNA-21 as an additional prognostic biomarker in patients with stage II
      colon cancer. Furthermore, the introduction of a risk index may guide the use of
      postoperative adjuvant treatment in a more appropriate way compared with current
      practice.

PMID- 25051408
TI  - Association between diabetes, diabetes treatment and risk of developing
      endometrial cancer.
AB  - BACKGROUND: A growing body of evidence suggests that diabetes is a risk factor
      for endometrial cancer incidence. However, most of these studies used case
      control study designs and did not adjust for obesity, an established risk factor
      for endometrial cancer. In addition, few epidemiological studies have examined
      the association between diabetes treatment and endometrial cancer risk. The
      objective of this study was to assess the relationships among diabetes, diabetes
      treatment and endometrial cancer risk in postmenopausal women participating in
      the Women's Health Initiative (WHI). METHODS: A total of 88 107 postmenopausal
      women aged 50-79 years who were free of cancer and had no hysterectomy at
      baseline were followed until date of endometrial cancer diagnosis, death,
      hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were
      confirmed by central medical record and pathology report review. Multivariate Cox
      proportional hazards regression models were used to estimate hazard ratios (HRs)
      (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment
      as risk factors for endometrial cancer. RESULTS: Over a mean of 11 years of
      follow-up, 1241 endometrial cancers developed. In the primary analysis that
      focused on prevalent diabetes at enrolment, compared with women without diabetes,
      women with self-reported diabetes, and the subset of women with treated diabetes,
      had significantly higher risk of endometrial cancer without adjusting for BMI
      (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated
      diabetes). However after adjusting for BMI, the associations between diabetes,
      diabetes treatment, diabetes duration and the risk of endometrial cancer became
      non-significant. Elevated risk was noted when considering combining diabetes
      diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31,
      95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was
      observed between metformin use and endometrial cancer risk. CONCLUSIONS: Our
      results suggest that the relationship observed in previous research between
      diabetes and endometrial cancer incidence may be largely confounded by body
      weight, although some modest independent elevated risk remains.

PMID- 25051409
TI  - Unique volatolomic signatures of TP53 and KRAS in lung cells.
AB  - BACKGROUND: Volatile organic compounds (VOCs) are potential biomarkers for cancer
      detection in breath, but it is unclear if they reflect specific mutations. To
      test this, we have compared human bronchial epithelial cell (HBEC) cell lines
      carrying the KRAS(V12) mutation, knockdown of TP53 or both with parental HBEC
      cells. METHODS: VOC from headspace above cultured cells were collected by passive
      sampling and analysed by thermal desorption gas chromatography mass spectrometry
      (TD-GC-MS) or sensor array with discriminant factor analysis (DFA). RESULTS: In
      TD-GC-MS analysis, individual compounds had limited ability to discriminate
      between cell lines, but by applying DFA analysis combinations of 20 VOCs
      successfully discriminated between all cell types (accuracies 80-100%, with leave
      one-out cross validation). Sensor array detection DFA demonstrated the ability to
      discriminate samples based on their cell type for all comparisons with accuracies
      varying between 77% and 93%. CONCLUSIONS: Our results demonstrate that minimal
      genetic changes in bronchial airway cells lead to detectable differences in
      levels of specific VOCs identified by TD-GC-MS or of patterns of VOCs identified
      by sensor array output. From the clinical aspect, these results suggest the
      possibility of breath analysis for detection of minimal genetic changes for
      earlier diagnosis or for genetic typing of lung cancers.

PMID- 25051412
TI  - Letter to the editor. Evaluation of mandibular lingual foramina.

PMID- 25051410
TI  - Updated investigations of cancer excesses in individuals born or resident in the
      vicinity of Sellafield and Dounreay.
AB  - BACKGROUND: Earlier studies have shown raised risks of leukaemia and non-Hodgkin
      lymphoma in children, teenagers and young adults resident either at birth or
      diagnosis in Seascale. Some increases in cancer risk in these age groups have
      also been noted among those living around Dounreay. We aimed to update previous
      analyses relating to areas close to these nuclear installations by considering
      data from an additional 16 years of follow-up. METHODS: Cross-sectional analyses
      compared cancer incidence rates for 1963-2006 among those aged 0-24 years at
      diagnosis living in geographically specified areas around either Sellafield or
      Dounreay with general population rates. Cancer incidence for the period 1971-2006
      among the cohort of Cumbrian births between 1950 and 2006 was compared to
      national incidence for 1971-2006 using person-years analysis. Cancer among those
      born in the postcode sector closest to Dounreay was compared with that among
      those born in the three adjoining postcode sectors. Analyses considered both
      cancer overall and ICD-O-3 defined diagnostic subgroups including leukaemia,
      central nervous system tumours and other malignancies. RESULTS: Apart from
      previously reported raised risks, no new significantly increased risks for cancer
      overall or any diagnostic subgroup were found among children or teenagers and
      young adults living around either nuclear installation. Individuals born close to
      the installations from 1950 to 2006 were not shown to be at any increased risk of
      cancer during the period 1971 to date. CONCLUSIONS: Analysis of recent data
      suggests that children, teenagers and young adults currently living close to
      Sellafield and Dounreay are not at an increased risk of developing cancer.
      Equally, there is no evidence of any increased cancer risk later in life among
      those resident in these areas at birth.

PMID- 25051413
TI  - Reply: To PMID 24394340.

PMID- 25051414
TI  - Novel CBCT and optical scanner-based implant treatment planning using a
      stereolithographic surgical guide: a multipronged diagnostic approach.
AB  - This report describes the use of the combination of 2 technologies (Cone-beam
      computed tomography and Optical 3-dimensional scan) to maximize accuracy of
      implant placement in an area where previous implants failed and had to be
      removed. This report also stresses the increased efficiency of combining
      technologies to fabricate stereolithographic surgical guide which, when used
      intraoperatively, can improve precision of placement. 

PMID- 25051415
TI  - Effect of locally applied bFGF on implant stability: biomechanical evaluation of
      2 different implant surfaces in rabbits.
AB  - OBJECTIVES: The aim of this study was to evaluate the implant stability with the
      addition of local application of basic fibroblast growth factor (bFGF) during the
      osseointegration of 2 different dental implant surfaces using rabbit tibia model.
      MATERIALS AND METHODS: Fifty-six dental implants, 28 of hydrophilic surface
      (SLActive) and 28 of hydrophobic surface (OsseoSpeed), were placed in 14 mature
      New Zealand rabbits. The rabbits each received both SLActive and OsseoSpeed
      implants per tibia, and bFGF was applied locally on 1 randomly selected tibia.
      Half of the subjects were killed at the fourth week of healing period, and the
      other half were killed at the twelfth week. Stabilization was assessed using
      resonance frequency analysis (RFA) and removal torque value (RTV). RESULTS: The
      local application of bFGF was found to enhance osseointegration, especially at
      the fourth week of healing period after application (P = 0.046). RFAs and RTVs
      were found to be higher in bFGF-treated implant with hydrophilic surfaces when
      compared with both bFGF-treated hydrophobic implants and nontreated hydrophilic
      controls. CONCLUSION: Local application of bFGF seems to increase the
      stabilization values in implants with hydrophilic surfaces and those with
      hydrophobic surfaces.

PMID- 25051416
TI  - Computed tomographic analysis of the mental foramen and nerve in Japanese
      patients.
AB  - PURPOSE: The aims of this study were to investigate the anatomical features of
      the mental foramen in Japanese patients through computed tomography (CT) imaging
      to reduce inadvertent damage to the mental nerve during implant placement.
      MATERIALS AND METHODS: The mandibles of 100 patients were observed on CT imaging.
      The location, shape, number, and size of the mental foramen were evaluated.
      Furthermore, the vertical and horizontal dimensions of the anterior loops were
      measured. RESULTS: The mental foramen was mainly located by the apex of the
      second mandibular premolar in male, whereas the mental foramen was mainly located
      by the apex of the second mandibular premolar and between the apex of the second
      premolar and the first mandibular molar in female. With exception of a few hemi
      mandibles, its shape was oval and the number of the mental foramen was 1. There
      was no significant difference in the size of the mental foramen between male and
      female. There was a significant difference in the vertical dimension of the
      anterior loops between the males and females. CONCLUSION: In general, altered lip
      sensations are preventable if the mental foramen is located, and this knowledge
      is employed when performing surgical procedures in the foraminal area.

PMID- 25051417
TI  - The impact of Helicobacter pylori on EGF, EGF receptor, and the c-erb-B2
      expression.
AB  - PURPOSE: Increased expression of epidermal growth factor (EGF), its receptor
      (EGFR), and c-erb-B2 protein, which is homological with the EGF receptor, in
      gastric mucosa, may play a role in gastric carcinogenesis. We assessed if the
      infection and eradication of Helicobacter pylori (H. pylori) affects the gastric
      expression of growth factors and serum gastrin concentrations. PATIENTS/METHODS:
      We examined immunohistochemically gastric EGF and both receptors' expression in:
      gastric cancer (GC; n=29), chronic gastritis with H. pylori infection (GHp+;
      n=40) before and after eradication and in patients without H. pylori infection
      (GHp-; n=42). RESULTS: Before the eradication therapy, gastric mucosal EGF and
      both receptor's expressions in GHp+ patients were increased compared to GHp-
      (p<0.05), but were similar to GC. After eradication, EGF and the receptor's
      expression significantly decreased in the gastric body. Both EGFR and c-erb-B2
      expression in the antrum were still higher than in GHp- (p<0.05), and remained
      comparable to GC. CONCLUSIONS: In patients with H. pylori infection the gastric
      mucosal EGF, EGFR, and c-erb-B2 expressions are similar to those observed in
      gastric cancer. The persistence of the antral expression of receptors after
      eradication, at a level comparable to the gastric cancer group, suggests their
      eventual role in the progression of changes initiated by H. pylori toward
      carcinogenesis.

PMID- 25051418
TI  - Epstein-Barr virus effect on frequency of functionally distinct T cell subsets in
      children with infectious mononucleosis.
AB  - PURPOSE: Epstein-Barr virus is a common human pathogen which infects the great
      majority of population worldwide. A striking proliferation of CD8+ T cells is an
      immune response to EBV invasion of B lymphocytes during infectious mononucleosis.
      The aim of the study was to analyze frequencies of CD28+CD95-, CD28+CD95+, CD28
      CD95+ T cell subsets putative naive (T(N)), central (T(CM)) and effector memory
      (T(EM)) T cells in children with infectious mononucleosis. MATERIAL/METHODS:
      Multiparameter flow cytometric analysis of CD4+ and CD8+ T cell subsets was
      performed in 19 children with acute infectious mononucleosis. RESULTS: The
      CD4+/CD8+ ratio was found to be decreased (0.53) in children with infectious
      mononucleosis. Median T(N), T(CM), T(EM) frequencies were estimated to be 3.7,
      4.5, 15.1% of CD8+ and 23, 59.3, 5.5% of CD4+ T cells, respectively. In the
      present study we demonstrated negative correlations between CD8+CD28+CD95+ and
      CD8+CD28-CD95+ T cells and both VCA IgM antibody titers and disease duration.
      However, no such correlation was found when subset of CD4+ T cells or
      CD8+CD28+CD95- cells was compared. CONCLUSIONS: We conclude that there is a rapid
      decrease in the number of memory CD8+ T cells in early acute stage of infectious
      mononucleosis.

PMID- 25051419
TI  - Influence of metabolic syndrome and its components on subclinical organ damage in
      hypertensive perimenopausal women.
AB  - PURPOSE: We investigated the association between metabolic syndrome (MS), its
      components and the presence of subclinical organ damage in hypertensive
      perimenopausal women. PATIENTS/METHODS: 152 women with newly diagnosed, untreated
      arterial hypertension (mean age 51.0 +/- 3.5 years) were included in the study.
      In all subjects anthropometrical measurements, 24-hr blood pressure monitoring,
      echocardiographic examination, and carotid ultrasound were performed. Carotid
      femoral pulse wave velocity (PWV) was measured to obtain data on vascular
      compliance. As the index of early kidney damage both glomerular filtration rate
      was calculated and albumin/creatinine ratio in the urine sample was measured. A
      fasting blood sample was taken to measure glucose and lipid concentration.
      RESULTS: MS was found in 41% of patients. Patients with MS exhibited elevated
      left ventricular mass index (LVMI 84.7 vs. 78.8 g/m(2.7), p=0.03), higher intima
      media thickness (IMT 0.67 vs. 0.62 mm, p=0.003), greater prevalence of LV
      hypertrophy (30% vs. 13%, p=0.01), and carotid plaques (24% vs. 15%, p=0.01). The
      multivariate regression analysis revealed that components of MS (systolic blood
      pressure and waist circumference) are stronger predictors of LVM than MS itself.
      The relationship between MS and LVMI lost its significance when BMI was included
      in the model, and remained significant for IMT. CONCLUSION: In hypertensive
      perimenopausal women components of MS are stronger predictors of subclinical
      organ damage than MS itself. Left ventricular mass and hypertrophy are more
      strongly correlated with increasing body weight than with the presence of MS. MS,
      independently of BMI, influences the level of subclinical atherosclerosis in the
      study group.

PMID- 25051420
TI  - Glycation is regulated by isoflavones.
AB  - The effect of soy isoflavones on the Maillard reaction (MR) was investigated.
      Model systems composed of the soy protein glycinin (10 mg mL(-1)) and fructose
      (40 mg mL(-1)) under basic pH (~12) conditions were employed for testing the anti
      glycative effect of the major antioxidant soy isoflavones (genistin and genistein
      at 10 MUg mL(-1)) and a soy isoflavone-rich extract. The contents of total
      phenols (TPCs) and total flavonoids (TFCs) of the isoflavone-rich extract were
      determined. Glycinin was pre-incubated with isoflavones for 1 h and 16 h at 60 
      degrees C prior to MR. The progress of MR was estimated by analysis of free amino
      groups by OPA assay; carbohydrate covalently bound to the protein backbone using
      phenol-sulfuric acid assay, protein-bound N(epsilon)-(carboxymethyl)lysine (CML)
      by UPLC-MS and spectral analysis of fluorescent protein-bound AGEs. Genistin (10
      MUg mL(-1), 23 MUM) and its aglycone genistein (10 MUg mL(-1), 37 MUM) did not
      prevent protein glycation (p > 0.05). The soy isoflavone-rich extract containing
      2.5 mg mL(-1) of TFC efficiently decreased the amount of carbohydrate bound to
      the protein skeleton (20%) (p < 0.05) and formation of advanced glycation end
      products (AGEs) (>80%) (p < 0.05). The anti-glycative mechanism of isoflavones
      may be related to its conjugation to glycation sites of the protein structure
      (free amino groups), their antioxidant character and trapping of dicarbonyl
      intermediates. Extracts based on mixtures of isoflavones may be useful for
      producing glycated conjugates avoiding the substantial formation of AGEs bound to
      protein. 

PMID- 25051422
TI  - Toward plasmonics with nanometer precision: nonlinear optics of helium-ion milled
      gold nanoantennas.
AB  - Plasmonic nanoantennas are versatile tools for coherently controlling and
      directing light on the nanoscale. For these antennas, current fabrication
      techniques such as electron beam lithography (EBL) or focused ion beam (FIB)
      milling with Ga(+)-ions routinely achieve feature sizes in the 10 nm range.
      However, they suffer increasingly from inherent limitations when a precision of
      single nanometers down to atomic length scales is required, where exciting
      quantum mechanical effects are expected to affect the nanoantenna optics. Here,
      we demonstrate that a combined approach of Ga(+)-FIB and milling-based He(+)-ion
      lithography (HIL) for the fabrication of nanoantennas offers to readily overcome
      some of these limitations. Gold bowtie antennas with 6 nm gap size were
      fabricated with single-nanometer accuracy and high reproducibility. Using third
      harmonic (TH) spectroscopy, we find a substantial enhancement of the nonlinear
      emission intensity of single HIL-antennas compared to those produced by state-of
      the-art gallium-based milling. Moreover, HIL-antennas show a vastly improved
      polarization contrast. This superior nonlinear performance of HIL-derived
      plasmonic structures is an excellent testimonial to the application of He(+)-ion
      beam milling for ultrahigh precision nanofabrication, which in turn can be viewed
      as a stepping stone to mastering quantum optical investigations in the near
      field. 

PMID- 25051421
TI  - WWOX modulates the gene expression profile in the T98G glioblastoma cell line
      rendering its phenotype less malignant.
AB  - The aim of the present study was to assess the influence of WWOX gene
      upregulation on the transcriptome and phenotype of the T98G glioblastoma cell
      line. The cells with high WWOX expression demonstrated a significantly different
      transcription profile for approximately 3,000 genes. The main cellular pathways
      affected were Wnt, TGFbeta, Notch and Hedgehog. Moreover, the WWOX-transfected
      cells proliferated at less than half the rate, exhibited greatly lowered adhesion
      to ECM, increased apoptosis and impaired 3D culture formation. They also
      demonstrated an increased ability for crossing the basement membrane. Our results
      indicate that WWOX, apart from its tumor-suppressor function, appears to be a key
      regulator of the main cellular functions of the cell cycle and apoptosis.
      Furthermore, our results showed that WWOX may be involved in controlling
      metabolism, cytoskeletal structure and differentiation. 

PMID- 25051424
TI  - Air pollutant emissions from on-road vehicles in China, 1999-2011.
AB  - The on-road vehicular emission in China from 1999 to 2011 was estimated, based on
      the emission factors of vehicles with different emission standards calculated by
      the COPERT model. The CO, NMVOC, NOX, BC and OC emissions changed from 19.7 Tg,
      4.4 Tg, 2.3 Tg, 47.1 Gg and 74.4 Gg in 1999 to 32.7 Tg, 4.1 Tg, 7.6 Tg, 177.6 Gg
      and 101.5 Gg in 2011, respectively. The general trend for CO, NOX and BC was
      increasing, while the tendency for NMVOC and OC was firstly increase before 2002
      and then decrease from 2003. The spatial analysis results showed that high
      emissions occurred in developed provinces (Guangdong, Shandong, Hebei, Jiangsu
      and Henan). The correlation between vehicular emissions and GDP were further
      investigated and good linear correlation was found. The not-obvious change of the
      inter-annual (1999-2011) fitted straight line slope and the sustained increasing
      emissions for NOX and BC suggested that the challenge of mitigating vehicular NOX
      and BC emissions is severe in China. The contribution from different vehicle
      types was also analyzed. Passenger car (PC) and motorcycle (MC) was the main
      contributor to the CO and NMVOC emissions. However, the contribution ratio of MC
      was decreasing from 36.6% and 68.8% in 1999 to 15.7% and 25.7% in 2011. Heavy
      duty truck (HDT) was the dominant contributor to NOX, BC and OC, with proportions
      of 58.9%, 57.6% and 52.8% in 2011, respectively. In addition, the uncertainty of
      the estimated emissions was also assessed based on the Monte Carlo simulation. 

PMID- 25051423
TI  - Incidence of ototoxicity in pediatric patients with transfusion-dependent
      thalassemia who are less well-chelated by mono- and combined therapy of iron
      chelating agents.
AB  - Ototoxicity due to iron chelation therapy, especially deferoxamine (DFO), is
      frequently observed in patients who have a higher chelation index (>0.025).
      However, there is limited data on patients who are less well-chelated and on
      other chelating regimens, including deferiprone (L1), deferasirox (DFX), and a
      combination of DFO and L1. To determine the incidence of ototoxicity from iron
      chelators, we retrospectively analyzed our clinical records from January 1997 to
      December 2010. All transfusion-dependent thalassemia (TDT) patients received iron
      chelation therapy with mono DFX, DFO, L1, or a combination. All patients
      underwent routine otolaryngologic examination and pure-tone audiometry before
      starting each chelation regimen and were regularly followed every 6 months. One
      hundred thalassemic patients were enrolled and analyzed (48 males and 52
      females), with a mean age of 12.11 +/- 4.48 years (range 2.5-22.5 years). Total
      summative duration of iron chelation therapy in all patients was 596.50 years.
      Nine patients were found to have conductive hearing loss. Sensorineural hearing
      loss (SNHL) was identified in seven patients but only four were determined to be
      associated with iron chelators; three patients were detected while undergoing DFO
      therapy and one patient with L1 therapy. None of patients undergoing DFO therapy
      had reached over the levels of chelation index. In our resource-limited setting
      with poor treatment compliance, there was a rather low incidence of ototoxicity
      after exposure to iron chelators. However, a routine audiometry remains
      recommended for early detection and intervention since SNHL still develops and
      results in a long-term morbidity.

PMID- 25051425
TI  - Relating metal exposure and chemical speciation to trace metal accumulation in
      aquatic insects under natural field conditions.
AB  - The present study investigated to what extent measured dissolved metal
      concentrations, WHAM-predicted free metal ion activity and modulating water
      chemistry factors can predict Ni, Cu, Zn, Cd and Pb accumulation in various
      aquatic insects under natural field conditions. Total dissolved concentrations
      and accumulated metal levels in four taxa (Leuctra sp., Simuliidae, Rhithrogena
      sp. and Perlodidae) were determined and free metal ion activities were calculated
      in 36 headwater streams located in the north-west part of England. Observed
      invertebrate body burdens were strongly related to free metal ion activities and
      competition among cations for uptake in the biota. Taking into account
      competitive effects generally provided better fits than considering uptake as a
      function of total dissolved metal levels or the free ion alone. Due to the
      critical importance and large range in pH (4.09 to 8.33), the H(+) ion activity
      was the most dominant factor influencing metal accumulation. Adding the influence
      of Na(+) on Cu(2+) accumulation improved the model goodness of fit for both
      Rhithrogena sp. and Perlodidae. Effects of hardness ions on metal accumulation
      were limited, indicating the minor influence of Ca(2+) and Mg(2+) on metal
      accumulation in soft-water streams (0.01 to 0.94 mM Ca; 0.02 to 0.39 mM Mg). DOC
      levels (ranging from 0.6 to 8.9 mg L(-1)) significantly affected Cu body burdens,
      however not the accumulation of the other metals. Our results suggest that 1)
      uptake and accumulation of free metal ions are most dominantly influenced by
      competition of free H(+) ions in low-hardness headwaters and 2) invertebrate body
      burdens in natural waters can be predicted based on the free metal ion activity
      using speciation modelling and effects of H(+) competition.

PMID- 25051426
TI  - NMDARs in neurological diseases: a potential therapeutic target.
AB  - N-methyl-D-aspartate ionotropic glutamate receptor (NMDARs) is a ligand-gated ion
      channel that plays a critical role in excitatory neurotransmission, brain
      development, synaptic plasticity associated with memory formation, central
      sensitization during persistent pain, excitotoxicity and neurodegenerative
      diseases in the central nervous system (CNS). Within iGluRs, NMDA receptors have
      been the most actively investigated for their role in neurological diseases,
      especially neurodegenerative pathologies such as Alzheimer's and Parkinson's
      diseases. It has been demonstrated that excessive activation of NMDA receptors
      (NMDARs) plays a key role in mediating some aspects of synaptic dysfunction in
      several CNS disorders, so extensive research has been directed on the discovery
      of compounds that are able to reduce NMDARs activity. This review discusses the
      role of NMDARs on neurological pathologies and the possible therapeutic use of
      agents that target this receptor. Additionally, we delve into the role of NMDARs
      in Alzheimer's and Parkinson's diseases and the receptor antagonists that have
      been tested on in vivo models of these pathologies. Finally, we put into
      consideration the importance of antioxidants to counteract oxidative capacity of
      the signaling cascade in which NMDARs are involved.

PMID- 25051427
TI  - Eccentric development of Balo's concentric sclerosis: detected by magnetic
      resonance diffusion-weighted imaging and magnetic resonance spectroscopy.
AB  - BACKGROUND: The concentricity of BCS has captured wide attention; the findings of
      the current study may provide useful information on the centrifugal pathogenesis
      of BCS. OBJECTIVE: This study aims to evaluate the performance of MRI, DWI and
      MRS in elucidating the pathogenesis of Balo's lesions expanding. METHODS: Six
      clinically diagnosed BCS cases were reviewed, and the findings obtained by MRI,
      DWI and MRS were analyzed. DWI data were available for six patients, with the DWI
      and ADC imaging locations being central and peripheral layers of the index
      lesion. At TE 144ms, we calculated metabolite ratios of MRS at different depths
      of the demyelinating lesions and compared with the lesion on the opposite normal
      side for two patients. RESULTS: The ADC values of 18 typical concentric lesions
      revealed that the central lesion had the highest ADC value, followed by the
      internal ring, and the outermost layer had the lowest ADC value. The reduction in
      NAA/Cr and the increase in Cho/Cr were more evident in the central lesion than in
      the internal and outermost ring. CONCLUSION: The findings of DWI and MRS indicate
      Balo's concentric rings develop gradually and centrifugally. Of course, this
      hypothesis remains to be proved by further experimental studies.

PMID- 25051428
TI  - Delayed admission to ICU does not increase the mortality of patients post
      neurosurgery.
AB  - Increasing shortage of intensive care resources is a worldwide problem. While
      routine postoperative admission to the intensive care unit (ICU) of patients
      undergoing neurosurgery is a long established practice for many hospitals.
      Therefore, some neurosurgical patients have to be cared in post anesthesia care
      unit (PACU) before ICU admission during high ICU occupancy. The aim of this study
      was to compare the outcome of neurosurgical patients immediately admitted to the
      ICU post operation with those who were required to wait for ICU bed in PACU and
      managed by anesthesiologists before ICU admission. All adult neurosurgical
      patients admitted to our ICU between January 2010 and July 2013 were
      retrospectively analyzed. Recorded data included demographic data, surgical
      categories, end time of operation, operation hours, postoperative complication,
      hospital/ICU length of stay and cost, Glasgow coma score (GCS) on ICU discharge
      and ICU mortality. A total of 989 neurosurgical patients were evaluated. Nine
      hundred thirty-seven (94.7%) patients were immediately admitted and 52 (5.3%)
      patients had delayed ICU admission. Median PACU waiting hours was 4.3 h
      (interquartile range: 2.0-10.2 h). Delayed ICU admission post neurosurgery was
      highly associated with the end time of operation (p = 0.019) and high ICU
      occupancy (p < 0.0001). Average GCS on ICU discharge was higher in immediately
      admitted group (13.0 +/- 3.5 vs. 11.4 +/- 4.5, p = 0.012). However, delayed
      admission to ICU post neurosurgery was not associated with prolonged ICU length
      of stay, increased ICU mortality, increased postoperative complication and
      hospital/ICU cost (all p > 0.05). Thus, an algorithm for appropriate disposition
      of neurosurgical patients is warranted so as to balance the quality of care and
      control of scarce intensive resources.

PMID- 25051429
TI  - Effects of housing conditions and season on the activity rhythm of spider monkeys
      (Ateles geoffroyi) kept under natural conditions within their distributional
      range in Central Mexico.
AB  - The timing and pattern of mammalian behavioral activities are regulated by an
      evolutionary optimized interplay of the genetically based biological (circadian)
      clock located in the brain's suprachiasmatic nuclei and direct responses to
      environmental factors that superimpose and thus mask the clock-mediated effects,
      the most important of which is the photically induced phase-setting
      (synchronization) of the circadian rhythmicity to the 24-hour solar day. In wild
      and captive animals living under the natural conditions prevailing in their
      habitat, to date, only a few attempts have been made to analyze the role of these
      two regulatory mechanisms in the species' adaptation to the time structure
      prevailing in their habitat. We studied the impact of housing conditions and
      season on the daily timing and pattern of activity in Mexican spider monkeys
      (Ateles geoffroyi). To this end, we carried out long-term activity recordings
      with Actiwatch(r) AW4 accelerometer/data-logger devices in 11 adult Ateles living
      under identical natural lighting and climatic conditions in either a large wire
      netting cage or a 0.25 ha forest enclosure in the primatological field station of
      Veracruz State University near Catemaco, Mexico. In a gravid female in the forest
      enclosure, we obtained first-hand information on the effect of late pregnancy and
      parturition on the monkey's activity rhythm. The Ateles behaved strictly diurnal
      and undertook about 90% of daily total activity during this activity time. Due to
      a higher second activity peak in late afternoon, the bimodal activity pattern was
      more pronounced in monkeys living in the forest enclosure. Although the spider
      monkeys kept there had an earlier activity onset and morning activity peak than
      their conspecifics in the cage, no consistent differences were found in the
      parameters characterizing the phase-setting of the circadian system to the
      environmental 24-h periodicity, either by comparison or correlation with the
      external time markers of sunrise (SR) and sunset (SS). The most obvious effect of
      late pregnancy, parturition and lactation was a distinct reduction of the
      activity level during the week of parturition and the next. Seasonal variations
      in the form of significant differences between the long-day summer half year and
      the short-day winter half year were established in the phase-angle differences of
      the morning activity peak to SR, in the evening activity peak and activity offset
      to SS, as well as in the activity time and the peak-to-peak interval, but not in
      the phase position of activity onset to SR or in the height of the morning and
      evening activity peak. These findings in combination with a high variability of
      the phase angle differences indicate that in A. geoffroyi, a relatively weak
      circadian component and strong masking direct effects of environmental factors
      are involved in the regulation of the daily activity rhythm. 

PMID- 25051431
TI  - Temperature sensitivity of circadian clocks is conserved across Drosophila
      species melanogaster, malerkotliana and ananassae.
AB  - Light and temperature are the major environmental cycles that can synchronize
      circadian rhythms in a variety of organisms. Previously, we have shown that under
      light/dark cycles of various photoperiods, the Drosophila species ananassae
      exhibits unimodal activity pattern with a prominent morning activity peak in
      contrast with Drosophila melanogaster and Drosophila malerkotliana, which show
      bimodal activity pattern with morning and evening activity peaks. Here we report
      that circadian clocks controlling activity/rest rhythm of these two less-studied
      species D. malerkotliana and D. ananassae can be synchronized by temperature
      cycles and that even under temperature cycles D. ananassae exhibits only a
      pronounced morning (thermophase onset) activity peak. Although D. melanogaster
      and D. ananassae exhibit differences in the phase of activity/rest rhythm under
      temperature cycles, circadian clocks of both show similar sensitivity to warm
      temperature pulses. Circadian period of activity/rest rhythm of D. ananassae
      differs from the other two species at some moderate-range temperatures; however,
      in conditions that are more extreme, circadian clocks of D. melanogaster, D.
      malerkotliana and D. ananassae appear to be largely temperature compensated. 

PMID- 25051430
TI  - Repeated psychosocial stress at night, but not day, affects the central molecular
      clock.
AB  - We have recently demonstrated that the outcome of repeated social defeat (SD) on
      behavior, physiology and immunology is more negative when applied during the
      dark/active phase as compared with the light/inactive phase of male C57BL/6 mice.
      Here, we investigated the effects of the same stress paradigm, which combines a
      psychosocial and novelty stressor, on the circadian clock in transgenic
      PERIOD2::LUCIFERASE (PER2::LUC) and wildtype (WT) mice by subjecting them to
      repeated SD, either in the early light phase (social defeat light = SDL) or in
      the early dark phase (social defeat dark = SDD) across 19 days. The PER2::LUC
      rhythms and clock gene mRNA expression were analyzed in the suprachiasmatic
      nucleus (SCN) and the adrenal gland, and PER2 protein expression in the SCN was
      assessed. SDD mice showed increased PER2::LUC rhythm amplitude in the SCN,
      reduced Per2 and Cryptochrome1 mRNA expression in the adrenal gland, and
      increased PER2 protein expression in the posterior part of the SCN compared with
      single-housed control (SHC) and SDL mice. In contrast, PER2::LUC rhythms in the
      SCN of SDL mice were not affected. However, SDL mice exhibited a 2-hour phase
      advance of the PER2::LUC rhythm in the adrenal gland compared to SHC mice.
      Furthermore, plasma levels of brain-derived neurotrophic factor (BDNF) and BDNF
      mRNA in the SCN were elevated in SDL mice. Taken together, these results show
      that the SCN molecular rhythmicity is affected by repeated SDD, but not SDL,
      while the adrenal peripheral clock is influenced mainly by SDL. The observed
      increase in BDNF in the SDL group may act to protect against the negative
      consequences of repeated psychosocial stress. 

PMID- 25051432
TI  - Parathyroid hormone-related protein: potential therapeutic target for melanoma
      invasion and metastasis.
AB  - The role of PTHrP in the highly metastatic human melanoma disease is not known.
      This study investigates the mechanisms of action of this secreted factor through
      homozygous inactivation of the Pthrp gene in A375 human melanoma cells. In vitro,
      Pthrp-ablated cells (knockout [KO]-A375, -/-) showed decreased motility and
      anchorage-independent growth, rounder morphology, and a significant reduction in
      invasion capacity compared with nonablated A375 cells (wild-type [WT]-A375, +/+).
      PTHrP peptide 1-34 and conditioned medium from WT-A375 cells partially restored
      the invasive phenotype in KO-A375. Pthrp ablation substantially decreased actin
      polymerization, matrix metallopeptidase 9 expression and focal adhesion kinase
      phosphorylation. In vivo, green fluorescent protein-transduced ablated and
      nonablated A375 cells were injected intracardially or sc into nude mice to study
      proliferation and multiorgan metastasis. Dissemination of injected Pthrp-ablated
      cells to lung and liver was reduced by 85% and 50%, respectively, compared with
      nonablated controls (120 hours after injection). The number of metastatic lesions
      and the percentage of animals with metastasis were markedly lower in mice
      injected with Pthrp-ablated A375, and 45% of these animals survived a 7-week
      period compared with 15% of mice injected with nonablated WT-A375. When mice
      injected with WT-A375 were treated with our blocking anti-PTHrP monoclonal
      antibody raised against the first 33 amino acids of human PTHrP, tumor size was
      decreased by more than 80% over 4 weeks and survival was significantly improved
      over 8 months. This study provides direct evidence of the major role for PTHrP in
      melanoma invasion and metastasis and suggests that agents that suppress PTHrP may
      be beneficial against melanoma progression.

PMID- 25051433
TI  - Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ
      mouse.
AB  - Type 2 diabetes (T2D) incidence in adolescents is rising and may interfere with
      peak bone mass acquisition. We tested the effects of early-onset T2D on bone
      mass, microarchitecture, and strength in the TALLYHO/JngJ mouse, which develops
      T2D by 8 weeks of age. We assessed metabolism and skeletal acquisition in male
      TALLYHO/JngJ and SWR/J controls (n = 8-10/group) from 4 weeks to 8 and 17 weeks
      of age. Tallyho mice were obese; had an approximately 2-fold higher leptin and
      percentage body fat; and had lower bone mineral density vs SWR at all time points
      (P < .03 for all). Tallyho had severe deficits in distal femur trabecular bone
      volume fraction (-54%), trabecular number (-27%), and connectivity density (-82%)
      (P < .01 for all). Bone formation was higher in Tallyho mice at 8 weeks but lower
      by 17 weeks of age vs SWR despite similar numbers of osteoblasts. Bone marrow
      adiposity was 7- to 50-fold higher in Tallyho vs SWR. In vitro, primary bone
      marrow stromal cell differentiation into osteoblast and adipocyte lineages was
      similar in SWR and Tallyho, suggesting skeletal deficits were not due to
      intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho
      mouse might be a useful model to study the skeletal effects of adolescent T2D.

PMID- 25051434
TI  - Overexpression of PPARgamma specifically in pancreatic beta-cells exacerbates
      obesity-induced glucose intolerance, reduces beta-cell mass, and alters islet
      lipid metabolism in male mice.
AB  - The contribution of peroxisomal proliferator-activated receptor (PPAR)-gamma
      agonism in pancreatic beta-cells to the antidiabetic actions of
      thiazolidinediones has not been clearly elucidated. Genetic models of pancreatic
      beta-cell PPARgamma ablation have revealed a potential role for PPARgamma in beta
      cell expansion in obesity but a limited role in normal beta-cell physiology. Here
      we overexpressed PPARgamma1 or PPARgamma2 specifically in pancreatic beta-cells
      of mice subjected to high-fat feeding using an associated adenovirus (beta
      PPARgamma1-HFD and beta-PPARgamma2-HFD mice). We show beta-cell-specific
      PPARgamma1 or PPARgamma2 overexpression in diet-induced obese mice exacerbated
      obesity-induced glucose intolerance with decreased beta-cell mass, increased
      islet cell apoptosis, and decreased plasma insulin compared with obese control
      mice (beta-eGFP-HFD mice). Analysis of islet lipid composition in beta-PPARgamma2
      HFD mice revealed no significant changes in islet triglyceride content and an
      increase in only one of eight ceramide species measured. Interestingly beta
      PPARgamma2-HFD islets had significantly lower levels of lysophosphatidylcholines,
      lipid species shown to enhance insulin secretion in beta-cells. Gene expression
      profiling revealed increased expression of uncoupling protein 2 and genes
      involved in fatty acid transport and beta-oxidation. In summary, transgenic
      overexpression of PPARgamma in beta-cells in diet-induced obesity negatively
      impacts whole-animal carbohydrate metabolism associated with altered islet lipid
      content, increased expression of beta-oxidative genes, and reduced beta-cell
      mass. 

PMID- 25051436
TI  - Estrogen receptor (ER) agonists differentially regulate neuroangiogenesis in
      peritoneal endometriosis via the repellent factor SLIT3.
AB  - Endometriosis is an estrogen-dependent neurovascular disorder characterized by
      growth of endometrial tissue (lesions) outside the uterine cavity. Patients
      suffer chronic pelvic pain, and it has been proposed that co-recruitment of
      nerves/blood vessels (neuroangiogenesis) into the lesions is fundamental to the
      development of painful symptoms. We hypothesized that estrogen-dependent
      regulation of axonal guidance molecules of the SLIT/ROBO (Roundabout) family
      could play a role in neuroangiogenesis occurring in endometriosis lesions found
      on the peritoneal wall. In tissue samples from human patients and a mouse model
      of endometriosis, concentrations of mRNA encoded by SLIT3 were significantly
      higher in lesions than normal peritoneum. Estrogen regulation of SLIT3 was
      investigated using 17beta-estradiol and selective agonists for each subtype of
      estrogen receptor (ER) (ERalpha agonist, 4,4',4"-(4-propyl-(1H)-pyrazole-1,3,5
      tryl) trisphenol; ERbeta agonist, 2,3-bis(4-hydroxy-phenyl)-propionitrile [DPN]).
      In mice, DPN (EC50 0.85) increased Slit3 mRNA concentrations compared with
      hormone-depleted and 17beta-estradiol-treated (EC50 0.1) animals and decreased
      the density of nerves but not vessels in endometriosis lesions. SLIT3 mRNA
      concentrations were increased in DPN-treated human endometrial endothelial cells
      and in 4,4',4"-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol-treated (EC50 200)
      rat dorsal root ganglia neurons. Functional assays (neurite outgrowth, network
      formation) revealed that SLIT3 promotes angiogenesis but decreases neurogenesis.
      In conclusion, these data suggest that estrogen-dependent expression of SLIT3 may
      play a key role in regulating nerve-vessel interactions within the complex
      microenvironment of endometriosis lesions.

PMID- 25051435
TI  - Placenta passage of the thyroid hormone analog DITPA to male wild-type and Mct8
      deficient mice.
AB  - Monocarboxylate transporter 8 (MCT8) deficiency causes severe X-linked
      intellectual and neuropsychological impairment associated with abnormal thyroid
      function tests (TFTs) producing thyroid hormone (TH) deprivation in brain and
      excess in peripheral tissues. The TH analog diiodothyropropionic acid (DITPA)
      corrected the TFTs abnormalities and hypermetabolism of MCT8-deficient children
      but did not improve the neurological phenotype. The latter result was attributed
      to the late initiation of treatment. Therefore, we gave DITPA to pregnant mice
      carrying Mct8-deficient embryos to determine whether DITPA, when given
      prenatally, crosses the placenta and affects the serum TFTs and cerebral cortex
      of embryos. After depletion of the endogenous TH, Mct8-heterozygous pregnant dams
      carrying both wild-type (Wt) and Mct8-deficient (Mct8KO) male embryos were given
      DITPA. Effects were compared with those treated with levothyroxine (L-T4). With
      DITPA treatment, serum DITPA concentration was not different in the two
      genotypes, which produced equal effect on serum TSH levels in both groups of
      pups. In contrast, with L-T4 treatment, TSH did not normalize in Mct8KO pups
      whereas it did in the Wt littermates and dams despite higher concentration of
      serum T4. Finally, both treatments similarly modulated the expression of the TH
      dependent genes Shh, Klf9, and Aldh1a3 in brain. Thus, the ability of DITPA to
      cross the placenta, its thyromimetic action on the expression of TH-dependent
      genes in brain, and its better accessibility to the pituitary than L-T4, as
      assessed by serum TSH, make DITPA a candidate for the prenatal treatment of MCT8
      deficiency.

PMID- 25051437
TI  - Cell-mass structures expressing the aromatase gene Cyp19a1 lead to ovarian
      cavities in Xenopus laevis.
AB  - The African clawed frog, Xenopus laevis, has a ZZ/ZW-type sex-determination
      system. We previously reported that a W-linked gene, Dm-W, can determine
      development as a female. However, the mechanisms of early sex differentiation
      remain unclear. We used microarrays to screen for genes with sexually dimorphic
      expression in ZZ and ZW gonads during early sex differentiation in X laevis and
      found several steroidogenic genes. Importantly, the steroid 17alpha-hydroxylase
      gene Cyp17a1 and the aromatase gene Cyp19a1 were highly expressed in ZZ and ZW
      gonads, respectively, just after sex determination. At this stage, we found that
      Cyp17a1, Cyp19a1, or both were expressed in the ZZ and ZW gonads in a unique mass
      in-line structure, in which several masses of cells, each surrounded by a
      basement membrane, were aligned along the anteroposterior axis. In fact, during
      sex differentiation, ovarian cavities formed inside each mass of Cyp17a1- and
      Cyp19a1-positive cells in the ZW gonads. However, the mass-in-line structure
      disappeared during testicular development in the ZZ testes. These results
      suggested that the mass-in-line structure found in both ZZ and ZW gonads just
      after sex determination might be formed in advance to produce ovarian cavities
      and then oocytes. Consequently, we propose a view that the default sex may be
      female in the morphological aspect of gonads in X laevis.

PMID- 25051439
TI  - Genetic rescue of glycosylation-deficient Fgf23 in the Galnt3 knockout mouse.
AB  - Fibroblast growth factor 23 (FGF23) is a hormone that inhibits renal phosphate
      reabsorption and 1,25-dihydroxyvitamin D biosynthesis. The FGF23 subtilisin-like
      proprotein convertase recognition sequence ((176)RHTR(179)?) is protected by O
      glycosylation through ppGalNAc-T3 (GALNT3) activity. Thus, inactivating GALNT3
      mutations render FGF23 susceptible to proteolysis, thereby reducing circulating
      intact hormone levels and leading to hyperphosphatemic familial tumoral
      calcinosis. To further delineate the role of glycosylation in the Fgf23 function,
      we generated an inducible FGF23 transgenic mouse expressing human mutant FGF23
      (R176Q and R179Q) found in patients with autosomal dominant hypophosphatemic
      rickets (ADHR) and bred this animal to Galnt3 knockout mice, a model of familial
      tumoral calcinosis. Due to the low intact Fgf23 level, Galnt3 knockout mice with
      wild-type Fgf23 alleles were hyperphosphatemic. In contrast, carriers of the
      mutant FGF23 transgene, regardless of Galnt3 mutation status, had significantly
      higher serum intact FGF23, resulting in severe hypophosphatemia. Importantly,
      serum phosphorus and FGF23 were comparable between transgenic mice with or
      without normal Galnt3 alleles. To determine whether the presence of the ADHR
      mutation could improve biochemical and skeletal abnormalities in Galnt3-null
      mice, these mice were also mated to Fgf23 knock-in mice, carrying heterozygous or
      homozygous R176Q ADHR Fgf23 mutations. The knock-in mice with functional Galnt3
      had normal Fgf23 but were slightly hypophosphatemic. The stabilized Fgf23 ADHR
      allele reversed the Galnt3-null phenotype and normalized total Fgf23, serum
      phosphorus, and bone Fgf23 mRNA. However, the skeletal phenotype was unaffected.
      In summary, these data demonstrate that O-glycosylation by ppGaINAc-T3 is only
      necessary for proper secretion of intact Fgf23 and, once secreted, does not
      affect Fgf23 function. Furthermore, the more stable Fgf23 ADHR mutant protein
      could normalize serum phosphorus in Galnt3 knockout mice.

PMID- 25051440
TI  - Disparate changes in kisspeptin and neurokinin B expression in the arcuate
      nucleus after sex steroid manipulation reveal differential regulation of the two
      KNDy peptides in rats.
AB  - Kisspeptin, neurokinin B (NKB) and dynorphin A are coexpressed in a population of
      neurons in the arcuate nucleus (ARC), termed KNDy neurons, which were recently
      recognized as important elements for the generation of GnRH pulses. However, the
      topographic distribution of these peptides and their regulated expression by sex
      steroids are still not well understood. In this study, detailed examination of
      NKB and kisspeptin immunoreactivity in the rat ARC was carried out, including
      comparison between sexes, with and without sex steroid replacement. Neurons
      expressing kisspeptin and NKB were more prominent in the caudal ARC of females,
      whereas neurons expressing NKB, but not kisspeptin, were the most abundant in the
      male. Sex steroid manipulation revealed differential regulation of kisspeptin and
      NKB; although kisspeptin immunoreactive (ir) cells increased in response to
      gonadectomy, NKB remained unchanged. Furthermore, the number of NKB-ir cells
      increased upon sex steroid replacement compared with gonadectomy, whereas
      kisspeptin did not, suggesting that sex steroids differently regulate these
      peptides. In addition, only in females did the density of kisspeptin- and NKB-ir
      fibers in the ARC increase upon sex steroid replacement in relation to sham and
      ovariectomy, respectively, suggesting sex-specific regulation of release. In
      conclusion, our observations reveal sex differences in the number of kisspeptin-
      and NKB-ir cells, which are more prominent in the caudal ARC. The divergent
      regulation of kisspeptin and NKB peptide contents in the ARC as a function of sex
      and steroid milieu enlarge our understanding on how these neuropeptides are
      posttranscriptionally regulated in KNDy neurons.

PMID- 25051438
TI  - Ezrin is an actin binding protein that regulates sertoli cell and spermatid
      adhesion during spermatogenesis.
AB  - During spermatogenesis, the transport of spermatids and the release of sperms at
      spermiation and the remodeling of the blood-testis barrier (BTB) in the
      seminiferous epithelium of rat testes require rapid reorganization of the actin
      based cytoskeleton. However, the mechanism(s) and the regulatory molecule(s)
      remain unexplored. Herein we report findings that unfold the functional
      significance of ezrin in the organization of the testis-specific adherens
      junction at the spermatid-Sertoli cell interface called apical ectoplasmic
      specialization (ES) in the adluminal compartment and the Sertoli cell-cell
      interface known as basal ES at the BTB. Ezrin is expressed at the basal ES/BTB in
      all stages, except from late VIII to IX, of the epithelial cycle. Its knockdown
      by RNA interference (RNAi) in vitro perturbs the Sertoli cell tight junction
      permeability barrier via a disruption of the actin microfilaments in Sertoli
      cells, which in turn impeded basal ES protein (eg, N-cadherin) distribution,
      perturbing the BTB function. These findings were confirmed by a knockdown study
      in vivo. However, the expression of ezrin at the apical ES is restricted to stage
      VIII of the cycle and limited only between step 19 spermatids and Sertoli cells.
      A knockdown of ezrin in vivo by RNAi was found to impede spermatid transport,
      causing defects in spermiation in which spermatids were embedded deep inside the
      epithelium, and associated with a loss of spermatid polarity. Also, ezrin was
      associated with residual bodies and phagosomes, and its knockdown by RNAi in the
      testis also impeded the transport of residual bodies/phagosomes from the apical
      to the basal compartment. In summary, ezrin is involved in regulating actin
      microfilament organization at the ES in rat testes.

PMID- 25051441
TI  - GLP-1 analog liraglutide enhances proinsulin processing in pancreatic beta-cells
      via a PKA-dependent pathway.
AB  - Hyperproinsulinemia has gained increasing attention in the development of type 2
      diabetes. Clinical studies have demonstrated that glucagon-like peptide-1 (GLP-1)
      based therapies significantly decrease plasma proinsulin/insulin ratio in
      patients with type 2 diabetes. However, the underlying mechanism remains unclear.
      Prohormone convertase (PC)-1/3 and PC2 are primarily responsible for processing
      proinsulin to insulin in pancreatic beta-cells. We have recently reported that
      Pax6 mutation down-regulated PC1/3 and PC2 expression, resulting in defective
      proinsulin processing in Pax6 heterozygous mutant (Pax6(m/+)) mice. In this
      study, we investigated whether and how liraglutide, a novel GLP-1 analog,
      modulated proinsulin processing. Our results showed that liraglutide
      significantly up-regulated PC1/3 expression and decreased the proinsulin to
      insulin ratio in both Pax6(m/+) and db/db diabetic mice. In the cultured mouse
      pancreatic beta-cell line, Min6, liraglutide stimulated PC1/3 and PC2 expression
      and lowered the proinsulin to insulin ratio in a dose- and time-dependent manner.
      Moreover, the beneficial effects of liraglutide on PC1/3 and PC2 expression and
      proinsulin processing were dependent on the GLP-1 receptor-mediated cAMP/protein
      kinase A signaling pathway. The same mechanism was recapitulated in isolated
      mouse islets. In conclusion, liraglutide enhanced PC1/3- and PC2-dependent
      proinsulin processing in pancreatic beta-cells through the activation of the GLP
      1 receptor/cAMP/protein kinase A signaling pathway. Our study provides a new
      mechanism for improvement of pancreatic beta-cell function by the GLP-1-based
      therapy.

PMID- 25051442
TI  - 5-HT obesity medication efficacy via POMC activation is maintained during aging.
AB  - The phenomenon commonly described as the middle-age spread is the result of
      elevated adiposity accumulation throughout adulthood until late middle-age. It is
      a clinical imperative to gain a greater understanding of the underpinnings of age
      dependent obesity and, in turn, how these mechanisms may impact the efficacy of
      obesity treatments. In particular, both obesity and aging are associated with
      rewiring of a principal brain pathway modulating energy homeostasis, promoting
      reduced activity of satiety pro-opiomelanocortin (POMC) neurons within the
      arcuate nucleus of the hypothalamus (ARC). Using a selective ARC-deficient POMC
      mouse line, here we report that former obesity medications augmenting endogenous
      5-hydroxytryptamine (5-HT) activity d-fenfluramine and sibutramine require ARC
      POMC neurons to elicit therapeutic appetite-suppressive effects. We next
      investigated whether age-related diminished ARC POMC activity therefore impacts
      the potency of 5-HT obesity pharmacotherapies, lorcaserin, d-fenfluramine, and
      sibutramine and report that all compounds reduced food intake to a comparable
      extent in both chow-fed young lean (3-5 months old) and middle-aged obese (12-14
      months old) male and female mice. We provide a mechanism through which 5-HT
      anorectic potency is maintained with age, via preserved 5-HT-POMC appetitive
      anatomical machinery. Specifically, the abundance and signaling of the primary 5
      HT receptor influencing appetite via POMC activation, the 5-HT2CR, is not
      perturbed with age. These data reveal that although 5-HT obesity medications
      require ARC POMC neurons to achieve appetitive effects, the anorectic efficacy is
      maintained with aging, findings of clinical significance to the global aging
      obese population.

PMID- 25051443
TI  - Estradiol stimulates apolipoprotein A-IV gene expression in the nucleus of the
      solitary tract through estrogen receptor-alpha.
AB  - Although estrogens have been implicated in the regulation of apolipoprotein A-IV
      (apo A-IV) gene expression in the nucleus tractus solitarius, previous studies
      have not defined the molecular mechanism. The aim of this study was to examine
      the transcriptional mechanisms involved in regulation of apo A-IV gene
      expression. Using cultured primary neuronal cells from rat embryonic brainstems,
      we found that treatment with 10nM 17beta-estradiol-3-benzoate (E2) or 4,4',4"-(4
      propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (an estrogen receptor [ER]alpha
      agonist), but not 2,3-bis(4-hydroxyphenyl)-propionitrile (an ERbeta agonist),
      significantly increased apo A-IV gene expression, compared with vehicle
      treatment. This effect of E2 was abolished when the cells were incubated with E2
      linked to BSA, which prevents E2 from entering cells, implying that a nongenomic
      mechanism of E2 is not involved. Two putative estrogen response elements were
      identified at the 5'-upstream region of the apo A-IV gene promoter, but only 1 of
      them was able to recruit ERalpha, leading to increased apo A-IV gene expression,
      as determined by chromatin immunoprecipitation assay and luciferase activity
      analysis. A cyclic regimen of E2 or 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl)
      trisphenol treatment for 8 cycles (4 d/cycle, mimicking the ovarian cycle of
      female rats) in ovariectomized female rats significantly reduced food intake and
      body weight gain and increased apo A-IV gene expression in the nucleus tractus
      solitarius, relative to vehicle. These data collectively demonstrate that nuclear
      ERalpha is the primary mediator of E2's action on apo A-IV gene expression and
      suggest that increased signaling of endogenous apo A-IV may at least partially
      mediate E2-induced inhibitory effect on feeding.

PMID- 25051444
TI  - Sexually dimorphic effects of ancestral exposure to vinclozolin on stress
      reactivity in rats.
AB  - How an individual responds to the environment depends upon both personal life
      history as well as inherited genetic and epigenetic factors from ancestors. Using
      a 2-hit, 3 generations apart model, we tested how F3 descendants of rats given in
      utero exposure to the environmental endocrine-disrupting chemical (EDC)
      vinclozolin reacted to stress during adolescence in their own lives, focusing on
      sexually dimorphic phenotypic outcomes. In adulthood, male and female F3
      vinclozolin- or vehicle-lineage rats, stressed or nonstressed, were behaviorally
      characterized on a battery of tests and then euthanized. Serum was used for
      hormone assays, and brains were used for quantitative PCR and transcriptome
      analyses. Results showed that the effects of ancestral exposure to vinclozolin
      converged with stress experienced during adolescence in a sexually dimorphic
      manner. Debilitating effects were seen at all levels of the phenotype, including
      physiology, behavior, brain metabolism, gene expression, and genome-wide
      transcriptome modifications in specific brain nuclei. Additionally, females were
      significantly more vulnerable than males to transgenerational effects of
      vinclozolin on anxiety but not sociality tests. This fundamental transformation
      occurs in a manner not predicted by the ancestral exposure or the proximate
      effects of stress during adolescence, an interaction we refer to as
      synchronicity.

PMID- 25051446
TI  - Nicotinic acetylcholine receptors in glucose homeostasis: the acute hyperglycemic
      and chronic insulin-sensitive effects of nicotine suggest dual opposing roles of
      the receptors in male mice.
AB  - Cigarette smoking causes insulin resistance. However, nicotine induces anti
      inflammation and improves glucose tolerance in insulin-resistant animal models.
      Here, we determined the effects of nicotine on glucose metabolism in insulin
      sensitive C57BL/J6 mice. Acute nicotine administration (30 min) caused fasting
      hyperglycemia and lowered insulin sensitivity acutely, which depended on the
      activation of nicotinic-acetylcholine receptors (nAChRs) and correlated with
      increased catecholamine secretion, nitric oxide (NO) production, and
      glycogenolysis. Chlorisondamine, an inhibitor of nAChRs, reduced acute nicotine
      induced hyperglycemia. qRT-PCR analysis revealed that the liver and muscle
      express predominantly beta4 > alpha10 > alpha3 > alpha7 and beta4 > alpha10 >
      beta1 > alpha1 mRNA for nAChR subunits respectively, whereas the adrenal gland
      expresses beta4 > alpha3 > alpha7 > alpha10 mRNA. Chronic nicotine treatment
      significantly suppressed expression of alpha3-nAChR (predominant peripheral alpha
      subunit) in liver. Whereas acute nicotine treatment raised plasma norepinephrine
      (NE) and epinephrine (Epi) levels, chronic nicotine exposure raised only Epi.
      Acute nicotine treatment raised both basal and glucose-stimulated insulin
      secretion (GSIS). After chronic nicotine treatment, basal insulin level was
      elevated, but GSIS after acute saline or nicotine treatment was blunted. Chronic
      nicotine exposure caused an increased buildup of NO in plasma and liver, leading
      to decreased glycogen storage, along with a concomitant suppression of Pepck and
      G6Pase mRNA, thus preventing hyperglycemia. The insulin-sensitizing effect of
      chronic nicotine was independent of weight loss. Chronic nicotine treatment
      enhanced PI-3-kinase activities and increased Akt and glycogen synthase kinase
      (GSK)-3beta phosphorylation in an nAChR-dependent manner coupled with decreased
      cAMP response element-binding protein (CREB) phosphorylation. The latter effects
      caused suppression of Pepck and G6Pase gene expression. Thus, nicotine causes
      both insulin resistance and insulin sensitivity depending on the duration of the
      treatment.

PMID- 25051445
TI  - Estrogen receptor inhibits mineralocorticoid receptor transcriptional regulatory
      function.
AB  - The steroid hormone aldosterone (aldo) contributes to cardiovascular disease in
      animal models and in humans. Aldo activates the mineralocorticoid receptor (MR),
      a hormone-activated transcription factor, and indeed, pharmacological MR
      inhibition improves cardiovascular outcomes. Because the incidence of
      cardiovascular disease is lower in premenopausal women, we hypothesized that
      estrogen (E2) signaling through the estrogen receptor (ER) may protect the
      vasculature by inhibiting the detrimental effects of aldo signaling through the
      MR. We demonstrate that E2-activated ER inhibits MR-mediated gene transcription
      from the mouse mammary tumor virus reporter in human embryonic kidney-293 cells.
      In contrast, aldo-activated MR does not affect ER-mediated gene transcription.
      The ERalpha N terminus (amino acids 1-253) containing part of the DNA-binding
      domain is sufficient to inhibit MR genomic function, although point mutations
      reveal that DNA binding, ligand-independent activation, and rapid nongenomic
      ERalpha signaling are not required for this effect. Furthermore, ERalpha and MR
      are part of a complex in cell lysates, with amino acids 1-233 of the ERalpha N
      terminus being sufficient to complex with the MR. Overall, the ability of ERalpha
      to inhibit MR-mediated gene transcription correlates with the ability of ERalpha
      segments to both localize to the nucleus and complex with the MR. In cultured
      vascular endothelial cells expressing ERalpha, E2 inhibits aldo induction of the
      vascular MR target gene intercellular adhesion molecule-1 (ICAM-1). ICAM-1
      induction by endothelial MR is known to promote vascular inflammation that could
      contribute to the mechanism of aldo-induced atherosclerosis. E2 also inhibits
      aldo induction of ICAM-1 protein and prevents aldo-enhanced leukocyte adhesion to
      endothelial cells. These studies support a new model in which E2-activated ER in
      endothelial cells forms a complex with MR in the nucleus to modulate MR
      regulation of the proinflammatory gene ICAM-1. Estrogen inhibition of MR
      regulation of genes that contribute to cardiovascular disease may be a new
      mechanism by which premenopausal women are protected from cardiovascular disease.

PMID- 25051447
TI  - Overexpression of corticotropin releasing factor in the central nucleus of the
      amygdala advances puberty and disrupts reproductive cycles in female rats.
AB  - Prolonged exposure to environmental stress activates the hypothalamic-pituitary
      adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal
      axis. Because CRF expression in the central nucleus of the amygdala (CeA) is a
      key modulator in adaptation to chronic stress, and central administration of CRF
      inhibits the hypothalamic GnRH pulse generator, we tested the hypothesis that
      overexpression of CRF in the CeA of female rats alters anxiety behavior,
      dysregulates the HPA axis response to stress, changes pubertal timing, and
      disrupts reproduction. We used a lentiviral vector to increase CRF expression
      site specifically in the CeA of preweaning (postnatal day 12) female rats.
      Overexpression of CRF in the CeA increased anxiety-like behavior in peripubertal
      rats shown by a reduction in time spent in the open arms of the elevated plus
      maze and a decrease in social interaction. Paradoxically, puberty onset was
      advanced but followed by irregular estrous cyclicity and an absence of
      spontaneous preovulatory LH surges associated with proestrous vaginal cytology in
      rats overexpressing CRF. Despite the absence of change in basal corticosterone
      secretion or induced by stress (lipopolysaccharide or restraint), overexpression
      of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint,
      stress-induced suppression of pulsatile LH secretion in postpubertal
      ovariectomized rats, indicating a differential stress responsivity of the GnRH
      pulse generator to immunological stress and a potential adaptation of the HPA
      axis to chronic activation of amygdaloid CRF. These data suggest that the
      expression profile of this key limbic brain CRF system might contribute to the
      complex neural mechanisms underlying the increasing incidence of early onset of
      puberty on the one hand and infertility on the other attributed to chronic stress
      in modern human society.

PMID- 25051448
TI  - A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA
      exposure in a prosocial species, the prairie vole (Microtus ochrogaster).
AB  - Impacts on brain and behavior have been reported in laboratory rodents after
      developmental exposure to bisphenol A (BPA), raising concerns about possible
      human effects. Epidemiological data suggest links between prenatal BPA exposure
      and altered affective behaviors in children, but potential mechanisms are
      unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have
      been proposed, but supporting evidence is minimal. To address these data gaps, we
      employed a novel animal model for neuroendocrine toxicology: the prairie vole
      (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and
      female prairie vole pups were orally exposed to 5-MUg/kg body weight (bw)/d, 50
      MUg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects
      were tested as juveniles in open field and novel social tests and for partner
      preference as adults. Brains were then collected and assessed for immunoreactive
      (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed
      nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in
      the paraventricular nucleus of the hypothalamus (PVN). Female open field activity
      indicated hyperactivity at the lowest dose and anxiety at the highest dose.
      Effects on social interactions were also observed, and partner preference
      formation was mildly inhibited at all dose levels. BPA masculinized principal bed
      nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50
      mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and
      fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated
      sex differences in PVN TH-ir neuron numbers and reversed this sex difference at
      the highest dose. Minimal behavioral effects were observed in BPA-exposed males.
      These data support the hypothesis that BPA alters affective behaviors,
      potentially via disruption of OT/AVP pathways.

PMID- 25051449
TI  - Maternal diet-induced obesity programs cardiovascular dysfunction in adult male
      mouse offspring independent of current body weight.
AB  - Obese pregnancies are not only associated with adverse consequences for the
      mother but also the long-term health of her child. Human studies have shown that
      individuals from obese mothers are at increased risk of premature death from
      cardiovascular disease (CVD), but are unable to define causality. This study
      aimed to determine causality using a mouse model of maternal diet-induced
      obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in
      simple sugars and saturated fat 6 weeks prior to pregnancy and throughout
      pregnancy and lactation. Control females were fed laboratory chow. Male offspring
      from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of
      age for gross cardiac morphometry using stereology, cardiomyocyte cell area by
      histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was
      assessed by isolated Langendorff technology at 12 weeks of age and hearts were
      analyzed at the protein level for the expression of the beta1 adrenergic
      receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in
      cardiac contraction. Offspring from obese mothers develop pathologic cardiac
      hypertrophy associated with re-expression of cardiac fetal genes. By young
      adulthood these offspring developed severe systolic and diastolic dysfunction and
      cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the
      absence of any change in corresponding body weight and despite the offspring
      eating a healthy low-fat diet. These findings provide a causal link to explain
      human observations relating maternal obesity with premature death from CVD in her
      offspring.

PMID- 25051450
TI  - Cnr2 deficiency confers resistance to inflammation-induced preterm birth in mice.
AB  - Infection-induced inflammation, frequently associated with increased production
      of proinflammatory cytokines, is considered a significant contributor to preterm
      birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is
      expressed in various immune cells and was shown to modulate immune responses. We
      show here that Cnr2, but not Cnr1, deficient mice are resistant to
      lipopolysaccharide (LPS)-driven preterm birth and suppression of serum
      progesterone levels. After LPS challenge, Cnr2(-/-) mice exhibited increased
      serum levels of IL-10 with decreased IL-6 levels. These changes were associated
      with reduced LPS-induced Ptgs2 expression at the maternal-conceptus interface on
      day 16 of pregnancy. LPS stimulation of Cnr2(-/-) dendritic cells in vitro
      resulted in increased IL-10 with reduced IL-6 production and correlated with
      increased cAMP accumulation. Collectively, our results suggest that increased IL
      10 production occurring via augmented cAMP accumulation represents a potential
      mechanism for the resistance of Cnr2(-/-) mice to LPS-induced preterm birth.
      These results may have clinical relevance, because currently, there are limited
      options to prevent preterm birth.

PMID- 25051452
TI  - A robust functional-data-analysis method for data recovery in multichannel sensor
      systems.
AB  - Multichannel sensor systems are widely used in condition monitoring for effective
      failure prevention of critical equipment or processes. However, loss of sensor
      readings due to malfunctions of sensors and/or communication has long been a
      hurdle to reliable operations of such integrated systems. Moreover, asynchronous
      data sampling and/or limited data transmission are usually seen in multiple
      sensor channels. To reliably perform fault diagnosis and prognosis in such
      operating environments, a data recovery method based on functional principal
      component analysis (FPCA) can be utilized. However, traditional FPCA methods are
      not robust to outliers and their capabilities are limited in recovering signals
      with strongly skewed distributions (i.e., lack of symmetry). This paper provides
      a robust data-recovery method based on functional data analysis to enhance the
      reliability of multichannel sensor systems. The method not only considers the
      possibly skewed distribution of each channel of signal trajectories, but is also
      capable of recovering missing data for both individual and correlated sensor
      channels with asynchronous data that may be sparse as well. In particular, grand
      median functions, rather than classical grand mean functions, are utilized for
      robust smoothing of sensor signals. Furthermore, the relationship between the
      functional scores of two correlated signals is modeled using multivariate
      functional regression to enhance the overall data-recovery capability. An
      experimental flow-control loop that mimics the operation of coolant-flow loop in
      a multimodular integral pressurized water reactor is used to demonstrate the
      effectiveness and adaptability of the proposed data-recovery method. The
      computational results illustrate that the proposed method is robust to outliers
      and more capable than the existing FPCA-based method in terms of the accuracy in
      recovering strongly skewed signals. In addition, turbofan engine data are also
      analyzed to verify the capability of the proposed method in recovering non-skewed
      signals. 

PMID- 25051451
TI  - Immunoglobulin heavy chain variable region and major histocompatibility region
      genes are linked to induced graves' disease in females from two very large
      families of recombinant inbred mice.
AB  - Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that
      mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism
      can be induced by immunizing mice with adenovirus expressing the human TSHR A
      subunit. Prior analysis of induced Graves' disease in small families of
      recombinant inbred (RI) female mice demonstrated strong genetic control but did
      not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated
      the genetic basis for induced Graves' disease in female mice of two large RI
      families and combined data with earlier findings to provide phenotypes for 178
      genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor
      were highly significantly linked in the BXD set to the major histocompatibility
      region (chromosome 17), consistent with observations in 3 other RI families. In
      the LXS family, we detected linkage between T4 levels after TSHR-adenovirus
      immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This
      observation is a key finding because components of the antigen binding region of
      Igs determine antibody specificity and have been previously linked to induced
      thyroid-stimulating antibodies. Data from the LXS family provide the first
      evidence in mice of a direct link between induced hyperthyroidism and Igvh genes.
      A role for major histocompatibility genes has now been established for genetic
      susceptibility to Graves' disease in both humans and mice. Future studies using
      arrays incorporating variation in the complex human Ig gene locus will be
      necessary to determine whether Igvh genes are also linked to Graves' disease in
      humans.

PMID- 25051453
TI  - Neuroprotective Xanthones from the Root Bark of Cudrania tricuspidata.
AB  - Seventeen new prenylated xanthones (1-17) were isolated from an ethyl acetate
      soluble extract of root bark of Cudrania tricuspidata together with 17 previously
      identified xanthones. The structures of the new compounds were elucidated by
      spectroscopic methods. Six new compounds (3, 7, 8, 9, 15, and 16) and six known
      compounds (18-23) showed neuroprotective effects against 6-hydroxydopamine
      induced cell death in human neuroblastoma SH-SY5Y cells, with EC50 values of 0.7
      16.6 MUM. 

PMID- 25051454
TI  - Exploiting the explosion of information associated with whole genome sequencing
      to tackle Shiga toxin-producing Escherichia coli (STEC) in global food production
      systems.
AB  - The rates of foodborne disease caused by gastrointestinal pathogens continue to
      be a concern in both the developed and developing worlds. The growing world
      population, the increasing complexity of agri-food networks and the wide range of
      foods now associated with STEC are potential drivers for increased risk of human
      disease. It is vital that new developments in technology, such as whole genome
      sequencing (WGS), are effectively utilized to help address the issues associated
      with these pathogenic microorganisms. This position paper, arising from an OECD
      funded workshop, provides a brief overview of next generation sequencing
      technologies and software. It then uses the agent-host-environment paradigm as a
      basis to investigate the potential benefits and pitfalls of WGS in the
      examination of (1) the evolution and virulence of STEC, (2) epidemiology from
      bedside diagnostics to investigations of outbreaks and sporadic cases and (3)
      food protection from routine analysis of foodstuffs to global food networks. A
      number of key recommendations are made that include: validation and
      standardization of acquisition, processing and storage of sequence data including
      the development of an open access "WGSNET"; building up of sequence databases
      from both prospective and retrospective isolates; development of a suite of open
      access software specific for STEC accessible to non-bioinformaticians that
      promotes understanding of both the computational and biological aspects of the
      problems at hand; prioritization of research funding to both produce and
      integrate genotypic and phenotypic information suitable for risk assessment;
      training to develop a supply of individuals working in bioinformatics/software
      development; training for clinicians, epidemiologists, the food industry and
      other stakeholders to ensure uptake of the technology and finally review of
      progress of implementation of WGS. Currently the benefits of WGS are being slowly
      teased out by academic, government, and industry or private sector researchers
      around the world. The next phase will require a coordinated international
      approach to ensure that it's potential to contribute to the challenge of STEC
      disease can be realized in a cost effective and timely manner. 

PMID- 25051455
TI  - Fast voltammetry of metals at carbon-fiber microelectrodes: copper adsorption
      onto activated carbon aids rapid electrochemical analysis.
AB  - Rapid, in situ trace metal analysis is essential for understanding many
      biological and environmental processes. For example, trace metals are thought to
      act as chemical messengers in the brain. In the environment, some of the most
      damaging pollution occurs when metals are rapidly mobilized and transported
      during hydrologic events (storms). Electrochemistry is attractive for in situ
      analysis, primarily because electrodes are compact, cheap and portable.
      Electrochemical techniques, however, do not traditionally report trace metals in
      real-time. In this work, we investigated the fundamental mechanisms of a novel
      method, based on fast-scan cyclic voltammetry (FSCV), that reports trace metals
      with sub-second temporal resolution at carbon-fiber microelectrodes (CFMs).
      Electrochemical methods and geochemical models were employed to find that
      activated CFMs rapidly adsorb copper, a phenomenon that greatly advances the
      temporal capabilities of electrochemistry. We established the thermodynamics of
      surface copper adsorption and the electrochemical nature of copper deposition
      onto CFMs and hence identified a unique adsorption-controlled electrochemical
      mechanism for ultra-fast trace metal analysis. This knowledge can be exploited in
      the future to increase the sensitivity and selectivity of CFMs for fast
      voltammetry of trace metals in a variety of biological and environmental models. 

PMID- 25051456
TI  - Electrochemical detection of the oligomerization of PB1-F2 influenza A virus
      protein in infected cells.
AB  - PB1-F2 is a nonstructural accessory protein of Influenza A virus described to
      enhance the mortality and the morbidity of the virus in a host-dependent manner.
      In this work, an electrochemical biosensor based on an immunodetection system was
      developed to follow the oligomerization of PB1-F2 during the viral cycle. The
      immunosensor was based on conductive polypyrrole modified with ferrocenyl groups
      as a redox marker for enhancing signal detection. Antibodies specific for
      monomeric or oligomeric PB1-F2 forms were immobilized on polypyrrole matrix via
      biotin/streptavidin layer. We demonstrated that this electrochemical biosensor
      sensitively detects PB1-F2 in both conformational forms. The linear range extends
      from 5 nM to 1.5 MUM and from 5 nM to 0.5 MUM for monomeric and oligomeric PB1
      F2, respectively. The calculated limit of detection was 0.42 nM for monomeric PB1
      F2 and 16 nM for oligomers. The biosensor platform allows the detection and
      quantification of PB1-F2 in lysates of infected cells during viral cycle. We show
      that at early stages of viral cycle, PB1-F2 is mainly monomeric but switched to
      amyloid-like structures at a later stage of infection. The quantification of two
      protein structural forms points out that PB1-F2 expression profiles and kinetics
      of oligomerization are cell-type-dependent. 

PMID- 25051458
TI  - Vertical nystagmus during the seated-supine positional (straight head-hanging)
      test in patients with benign paroxysmal positional vertigo.
AB  - OBJECTIVE: This study describes the clinical features of up-beating vertical
      nystagmus observed during the seated-supine positional (straight head-hanging)
      test in patients with benign paroxysmal positional vertigo. METHODS: A total of
      190 patients with benign paroxysmal positional vertigo symptoms who had presented
      between 2009 and 2012 were enrolled for this retrospective case series. Twelve
      patients with positional up-beating vertical nystagmus, as confirmed by video
      nystagmography during the seated-supine positional test, were selected. RESULTS:
      The incidence and duration of symptoms of multiple canal benign paroxysmal
      positional vertigo were significantly lower compared with the other types of
      benign paroxysmal positional vertigo (p = 0.029 and p = 0.048 respectively).
      Trauma was the leading aetiological factor in those patients (p = 0.012). The
      average number of therapeutic manoeuvres required for the relief of symptoms in
      patients with multiple canal involvement was significantly higher than in the
      other groups (p = 0.041). CONCLUSION: In patients with benign paroxysmal
      positional vertigo, the presence of vertical up-beating nystagmus while lying
      down is a unique peripheral sign and could indicate multiple canal involvement.
      Therefore, the seated-supine positional test should always be included in the
      test battery.

PMID- 25051457
TI  - Experimental and computational investigation of the effect of hydrophobicity on
      aggregation and osteoinductive potential of BMP-2-derived peptide in a hydrogel
      matrix.
AB  - An attractive approach to reduce the undesired side effects of bone morphogenetic
      proteins (BMPs) in regenerative medicine is to use osteoinductive peptide
      sequences derived from BMPs. Although the structure and function of BMPs have
      been studied extensively, there is limited data on structure and activity of BMP
      derived peptides immobilized in hydrogels. The objective of this work was to
      investigate the effect of concentration and hydrophobicity of the BMP-2 peptide,
      corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on
      peptide aggregation and osteogenic differentiation of human mesenchymal stem
      cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide
      hydrophobicity was varied by capping PEG chain ends with short lactide segments.
      The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle
      concentration (CMC) and formed aggregates in aqueous solution. Based on
      simulation results, there was a slight increase in the concentration of free
      peptide in solution with 1000-fold increase in peptide concentration. The dose
      osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range,
      and osteoinductive potential of the BMP-2 peptide was significantly less than
      that of BMP-2 protein even at 1000-fold higher concentrations, which was
      attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates
      had significantly higher interaction energy with the cell membrane compared with
      the free peptide, which led to a higher nonspecific interaction with the cell
      membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide
      to PEG increased CMC and osteoinductive potential of the peptide whereas
      conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the
      peptide. Experimental and simulation results revealed that osteoinductive
      potential of the BMP-2 peptide is correlated with its CMC and the free peptide
      concentration in aqueous medium and not the total concentration. 

PMID- 25051459
TI  - Gadolinium enhanced 3D proton density driven equilibrium MR imaging in the
      evaluation of cisternal tumor and associated structures: comparison with balanced
      fast-field-echo sequence.
AB  - OBJECTIVES: Although Gadolinium enhanced bFFE is commonly used to evaluate
      cisternal tumors, banding artifact may interrupt interpretation and adjacent
      nerve and vessels differentiation is known to be difficult. We analyzed the
      qualities of Gd enhanced 3D PDDE in the evaluation of cisternal tumors, comparing
      with bFFE. MATERIAL AND METHODS: Forty five cisternal tumors (33 schwannoma and
      12 meningioma) on both bFFE and PDDE were retrospectively reviewed. For
      quantitative analysis, contrast ratios of CSF to tumor and tumor to parenchyma
      (CRC/T and CRT/P) on both sequences were compared by paired t-test. For
      qualitative analysis, the readers gauged the qualities of the two MR sequences
      with respect to the degree of demarcating cisternal structures (tumor, basilar
      artery, AICA, trigeminal nerve, facial nerve and vestibulocochlear nerve).
      RESULTS: In quantitative analysis, CRC/T and CRT/P on 3D PDDE was significantly
      lower than that of 3D bFFE (p < 0.01). In qualitative analysis, basilar artery,
      AICA, facial nerve and vestibulocochlear nerves were significantly better
      demarcated on 3D PDDE than on bFFE (p < 0.01). The degree of demarcation of tumor
      on 3D PDDE was not significantly different with that on 3D bFFE (p = 0.13).
      CONCLUSION: Although the contrast between tumor and the surrounding structures
      are reduced, Gd enhanced 3D PDDE provides better demarcation of cranial nerves
      and major vessels adjacent to cisternal tumors than Gd enhanced bFFE.

PMID- 25051461
TI  - Specific binding of Zn2+, Cd2+ and Ni2+ ions by a cyclic four-cysteinyl peptide.
AB  - The metal binding abilities of the GCASCDNCRACKK cyclic peptide towards Zn(2+),
      Cd(2+) and Ni(2+) ions were studied by potentiometric and spectroscopic methods.
      The aim of this work was to understand the impact of cyclization on the peptide
      binding mode and the stability of the formed metal complexes when compared to its
      linear Ac-GCASCDNCRACKK-NH2 analogue. The obtained results clearly indicate that
      in the case of Cd(2+) and Ni(2+) complexes, the cyclization of the coordinating
      peptide distinctly increases the complex stability in the whole pH range studied.
      Surprisingly, different results were obtained for Zn(2+) complexes. The peptide
      cyclization seems to prevent the binding of all four available cysteinyl residues
      to the Zn(2+) ion, resulting in the reduced stability of the respective
      complexes. 

PMID- 25051460
TI  - Inpatient rehabilitation performance of patients with paraneoplastic cerebellar
      degeneration.
AB  - OBJECTIVE: To evaluate the functional improvement of rehabilitation inpatients
      with paraneoplastic cerebellar degeneration. DESIGN: Retrospective review.
      SETTING: Referral-based hospitals. PARTICIPANTS: Cancer rehabilitation inpatients
      (N=7) admitted to 3 different cancer centers with a diagnosis of paraneoplastic
      cerebellar degeneration. INTERVENTION: Medical records were retrospectively
      analyzed for demographic, laboratory, medical, and functional data. MAIN OUTCOME
      MEASURE: FIM. RESULTS: All 7 patients were white women (median age, 62y). Primary
      cancers included ovarian carcinoma (n=2), small cell lung cancer (n=2), uterine
      carcinoma (n=2), and invasive ductal breast carcinoma (n=1). Mean admission total
      FIM score was 61+/-23.97. Mean discharge total FIM score was 73.6+/-29.35. The
      mean change in total FIM score was 12.6 (P=.0018). The mean length of
      rehabilitation stay was 17.1 days. The mean total FIM efficiency was .73. Of the
      7 patients, 5 (71%) were discharged home, 1 (14%) was discharged to a nursing
      home, and 1 (14%) was transferred to the primary acute care service. CONCLUSIONS:
      To our knowledge, this is the first study to demonstrate the functional
      performance of a group of rehabilitation inpatients with paraneoplastic
      cerebellar degeneration. Despite the poor neurologic prognosis associated with
      this syndrome, these patients made significant functional improvements in
      inpatient rehabilitation. When appropriate, inpatient rehabilitation should be
      considered. Further studies with larger sample sizes are needed.

PMID- 25051462
TI  - Sustainable development in Tibet requires control of agricultural nonpoint
      pollution.

PMID- 25051463
TI  - Real-time process dynamics monitoring in Anammox reactors.
AB  - Process dynamics in Anammox systems were evaluated through continuous monitoring
      of pH, oxidation reduction potential (ORP) and conductivity in two separate newly
      started-up sequencing batch reactors, one seeded with an enriched Anammox sludge
      and the other seeded with mixed activated sludge. The pH and ORP profiles
      exhibited characteristic patterns depending on the process dynamics during early
      start-up, start-up and enrichment phases of the operational period of 410 days.
      The simultaneously continuing processes of the start-up period showed apparent
      indicative trend lines in pH and ORP profiles. Conductivity profiles were
      consistent with the process dynamics in all phases. During the enrichment phase,
      conductivity decreases could quantitatively be related to process removal
      efficiencies and all real-time profiles exhibited specific break-points which
      coincided with the end of Anammox in each cycle. The end of Anammox was observed
      as an 'apex' on pH profiles and a 'valley' on ORP profiles. The 'apex' and
      'valley' points exactly coincided with the end point of the linear decrease in
      the conductivity profiles. The overall findings suggested a great potential in
      using real-time pH, ORP and conductivity measurements for quick and reliable
      monitoring of Anammox systems during start-up and enrichment periods. 

PMID- 25051464
TI  - Continuous fixed bed adsorption of Cu(II) by halloysite nanotube-alginate hybrid
      beads: an experimental and modelling study.
AB  - We used natural resources of halloysite nanotubes and alginate to prepare a novel
      porous adsorption material of organic-inorganic hybrid beads. The adsorption
      behaviour of Cu(II) onto the hybrid beads was examined by a continuous fixed bed
      column adsorption experiment. Meanwhile, the factors affecting the adsorption
      capacity such as bed height, influent concentration and flow rate were
      investigated. The adsorption capacity (Q0) reached 74.13 mg/g when the initial
      inlet concentration was 100 mg/L with a bed height of 12 cm and flow rate of 3
      ml/min. The Thomas model and bed-depth service time fitted well with the
      experimental data. In the regeneration experiment, the hybrid beads retained high
      adsorption capacity after three adsorption-desorption cycles. Over the whole
      study, the new hybrid beads showed excellent adsorption and regeneration
      properties as well as favourable stability. 

PMID- 25051465
TI  - Optimized culture condition for enhancing lytic performance of waste activated
      sludge by Geobacillus sp. G1.
AB  - Hydrolysis is known as the rate-limiting step during waste activated sludge (WAS)
      digestion. The optimization of the culture conditions of Geobacillus sp. G1 for
      enhancing WAS hydrolysis was conducted in this study with uniform design and
      response surface methodology. Taking the lysis rate of Escherichia coli as the
      response, the Plackett-Burman design was used to screen the most important
      variables. Experimental results showed that the maximum predicted lysis rate of
      E. coli was 50.9% for 4 h treatment time with concentrations of skim milk, NaCl
      and NH4SO4 at 10.78, 4.36 and 11.28 g/L, respectively. The optimized dosage ratio
      of Geobacillus sp. G1 to WAS was 35%:65% (VG1:VWAS). Under this condition,
      soluble protein was increased to 695 mg chemical oxygen demand (COD)/L, which was
      5.0 times higher than that obtained in the control (140 mg COD/L). The
      corresponding protease activity reached 1.1 Eu/mL. Scanning electron microscopy
      showed that abundant cells were apparently lysed with treatment of Geobacillus
      sp. G1. 

PMID- 25051466
TI  - Treatment of iron(II)-rich acid mine water with limestone and oxygen.
AB  - The main components of acid mine water are free acid, sulphate, and Fe2+.
      Limestone is the most cost-effective alkali that can be used for neutralization.
      The purpose of this investigation was to identify conditions where Fe2+ is
      removed with limestone and simultaneously oxidized with oxygen to Fe3+, in a
      polyvinyl chloride pipe under pressure. Gypsum scaling is prevented by passing
      rubber balls through the pipe of the so-called Oxygen-Pipe-Neutralization (OPeN)
      process pilot plant. Two synthetic waters were treated: (A) acid mine water
      containing 123 mg L-1 Fe2+ representing gold mine water, and (B) acid mine water
      containing 6,032 mg L-1 Fe2+ representing coal mine water. Batch studies were
      carried out in a pipe reactor and showed that the rate of Fe2+ oxidation depended
      on the Fe2+ concentration, oxygen pressure, amount of recycled sludge, limestone
      dosage and the mixing rate. Continuous studies in an OPeN process pilot plant
      resulted in 100% removal of total acidity from synthetic coal mine water and a
      98% removal from synthetic gold mine water. Fe2+ was removed completely as
      precipitated Fe(OH)3 from both synthetic coal and gold mine water at around pH 7
      at 200 and 100 kPa oxygen pressure, respectively.

PMID- 25051467
TI  - Stormwater runoff quality in correlation to land use and land cover development
      in Yongin, South Korea.
AB  - Stormwater runoff quality is sensitive to land use and land cover (LULC) change.
      It is difficult to understand their relationship in predicting the pollution
      potential and developing watershed management practices to eliminate or reduce
      the pollution risk. In this study, the relationship between LULC change and
      stormwater runoff quality in two separate monitoring sites comprising a
      construction area (Site 1) and mixed land use (Site 2) was analyzed using
      geographic information system (GIS), event mean concentration (EMC), and
      correlation analysis. It was detected that bare land area increased, while other
      land use areas such as agriculture, commercial, forest, grassland, parking lot,
      residential, and road reduced. Based on the analyses performed, high maximum
      range and average EMCs were found in Site 2 for most of the water pollutants.
      Also, urban areas and increased conversion of LULC into bare land corresponded to
      degradation of stormwater quality. Correlation analysis between LULC and
      stormwater quality showed the influence of different factors such as farming
      practices, geographical location, and amount of precipitation, vegetation loss,
      and anthropogenic activities in monitoring sites. This research found that GIS
      application was an efficient tool for monthly monitoring, validation and
      statistical analysis of LULC change in the study area. 

PMID- 25051468
TI  - Performance evaluation and spatial sludge distribution at facultative and
      maturation ponds treating wastewater from an international airport.
AB  - This paper presents a performance evaluation of facultative and maturation ponds
      in series treating wastewater from a large and intensively used international
      airport in Brazil, based on 16 years of regular monitoring. The wastewater from
      the airport showed similar or slightly lower concentrations compared to typical
      domestic sewage for most of the quality parameters. The contribution of effluents
      with possible industrial features (aircraft toilets and hangar effluent) did not
      seem to have adversely affected the characteristics of the influent in terms of
      aptitude to biological treatment. Overall, the ponds operated under very
      underloaded conditions (mean loading rate of 44 kg biochemical oxygen demand/ha.d
      in the facultative pond) and presented a satisfactory quality in terms of
      effluent concentrations for most parameters. A bathymetric survey of the ponds
      was done manually by a low-cost measurer constructed specifically for this
      purpose. After 27 years of operation, only 25% and 18% of the volumes of the
      facultative and maturation ponds were occupied by sludge. Specific sludge
      accumulation rates were 0.0071 m3/passenger.year for the facultative pond and
      0.00017 m3/passenger.year for the maturation pond. 

PMID- 25051469
TI  - Exponential fed-batch strategy for enhancing biosurfactant production by Bacillus
      subtilis.
AB  - Surfactin produced by Bacillus subtilis BDCC-TUSA-3 from Maldex-15 was used as a
      growth-associated product in a conventional batch process. Maldex-15 is a cheap
      industrial by-product recovered during manufacturing of high fructose syrup from
      corn starch. Surfactin production was greatly improved in exponential fed-batch
      fermentation. Maldex-15 and other nutrients were exponentially fed into the
      culture based on the specific growth rate of the bacterium. In order to maximize
      surfactin yield and productivity, conversion of different quantities of Maldex-15
      into surfactin was investigated in five different fermentation runs. In all runs,
      most of the Maldex-15 was consumed and converted into surfactin and cell biomass
      with appreciable efficiencies. The best results were obtained with the
      fermentation run supplied with 204 g Maldex-15. Up to 36.1 g l(-1) of surfactin
      and cell biomass of 31.8 g l(-1) were achieved in 12 h. Also, a marked substrate
      yield of 0.272 g g(-1) and volumetric reactor productivity of 2.58 g 1(-1) h(-1)
      were obtained, confirming the establishment of a cost-effective commercial
      surfactin production. 

PMID- 25051470
TI  - Effect of biofilm on colloid attachment in saturated porous media.
AB  - Biofilm plays an important role in controlling the transport of colloids in a
      porous media. Biofilms are formed when micro-organisms come in contact with
      substrates, and are able to attach and grow with availability of nutrients. The
      microorganisms get embedded in a matrix of the substrate and extracellular
      polymeric substances which are responsible for the morphology, physico-chemical
      properties, structure and coherence of the biofilm. In this study, the effect of
      biofilm and its aging on colloid removal was studied on a glass bead column.
      Oocysts, polystyrene microspheres and inorganic colloids were used as colloidal
      particles. Pseudomonas aeruginosa was used as a model biofilm-forming
      microorganism. Presence of biofilm significantly enhanced colloid removal in the
      column. After 3 weeks, almost complete colloid removal was observed. The
      formation of biofilm was confirmed by various physical characterization
      techniques. During the extended aging study, biofilm sloughed off under shear
      stress. The loss of biofilm was higher during the early stage of its growth, and
      subsequently slowed down probably due to the formation of a more rigid biofilm.
      This research indicates that biofilm formation, maturation and sloughing-off play
      a critical role in colloid removal through porous media. 

PMID- 25051471
TI  - Investigating the influence of elongated anaerobic feeding strategy on aerobic
      sludge granulation and characteristics in sequencing batch reactor.
AB  - In this research, two sequencing batch reactors (R1 and R2) were operated with
      different feeding strategies to investigate the effects of elongated anaerobic
      feeding mode on the granulation process. For this purpose, R1 was operated in a
      short-feed strategy (5 min) as a reference, whereas an extended anaerobic feeding
      of 85 min was applied in R2. Results showed that aerobic granules formed in R1
      were denser and more uniform with lower sludge volume index than those formed in
      R2. Investigation of tightly bound extracellular polymeric substances (TB-EPS)
      showed that aerobic granules in R1 produced lower amounts of TB-EPS than those in
      R2. This was due to the bigger and more compact granules cultivated in R1 in
      comparison with looser structure granules in R2 with higher flocculent sludge
      percentage. The relative hydrophobicity of granules in both reactors was
      increased with culture time and reached about 63 and 65% at day 70 for R1 and R2,
      respectively. Moreover, no significant correlation between protein/polysaccharide
      ratio and hydrophobicity was found, which showed that protein in loosely bound
      extracellular polymer substances was not the predominant hydrophobic component.
      Considering the outcomes of this study, it can be concluded that the elongated
      anaerobic feeding strategy was unfavourable for cultivating aerobic granules. 

PMID- 25051472
TI  - Longitudinal and transverse dispersion coefficients in braided rivers.
AB  - The dispersion characteristics of braided rivers are presently unclear. The
      comprehensive flow structure in a physical braided river model was measured and
      was used to estimate its dispersion coefficient tensor. The largest values of the
      longitudinal and transverse dispersion coefficients occurred in the separation
      zone in two anabranches. The separation zone disappeared in a small diversion
      angle model of braided rivers where the coefficients were smaller. As for the
      sectional transverse distribution, the two coefficients varied markedly and an
      interesting negative correlation between them appeared in several sections. The
      dispersion coefficients increased with upstream flow rates. Comparison between
      the coefficients for different anabranch widths revealed higher values in wider
      sections. Finally, the values of the laboratory tests were compared with those in
      a real braided river, and relatively larger coefficients were found in natural
      rivers. The findings of this paper could be helpful in understanding the
      dispersion characteristics and in estimating pollutant concentration in braided
      rivers. 

PMID- 25051473
TI  - Evaluation of the aerobic and anaerobic biodegradability of the antibiotic
      norfloxacin.
AB  - The purpose of studying the biodegradability of pharmaceutical compounds is to
      evaluate their behaviors in relation to the treatment processes generally used in
      domestic and industrial wastewater treatment plants. The antibiotic norfloxacin
      was found to be a recalcitrant compound. The studies conducted showed norfloxacin
      removal rates of 12% and 18% when biomasses from treatments with activated sludge
      and anaerobic biodigesters, respectively, were used without acclimatization. This
      suggests that anaerobic digestion shows better performance for norfloxacin
      removal. Ecotoxicological tests, using the luminescent marine bacteria Aliivibrio
      fischeri as the test organism, show that anaerobic digestion could eliminate the
      toxicity of the antibiotic norfloxacin, even though total degradation of the drug
      was not observed. The release of norfloxacin during cell lysis suggests the
      importance of controlling this phenomenon in biological treatment systems that
      handle wastewater contaminated with norfloxacin, thus preventing the return of
      this drug to the environment. 

PMID- 25051474
TI  - SANASA Capivari II - the first full-scale municipal membrane bioreactor in Latin
      America.
AB  - The macro region of Campinas (Brazil) is rapidly evolving with new housing
      developments and industries, creating the challenge of finding new ways to treat
      wastewater to a quality that can be reused in order to overcome water scarcity
      problems. To address this challenge, SANASA (a publicly owned water and
      wastewater concessionaire from Campinas) has recently constructed the 'EPAR
      (Water Reuse Production Plant) Capivari II' using the GE ZeeWeed 500D((r))
      ultrafiltration membrane system. This is the first large-scale membrane
      bioreactor (MBR) system in Latin America with biological tertiary treatment
      capability (nitrogen and phosphorus removal), being able to treat an average flow
      of 182 L/s in its first phase of construction. The filtration system is composed
      of three membrane trains with more than 36,000 m(2) of total membrane filtration
      area. The membrane bioreactor (MBR) plant was commissioned in April 2012 and the
      permeate quality has exceeded expectations. Chemical oxygen demand (COD) removal
      rates are around and above 97% on a consistent basis, with biochemical oxygen
      demand (BOD5) and NH3 (ammonia) concentrations at very low levels, and turbidity
      lower than 0.3 nephelometric turbidity unit (NTU). Treated effluent is sent to a
      water reuse accumulation tank (from where will be distributed as reuse water),
      and the excess is discharged into the Capivari River. 

PMID- 25051475
TI  - Ten years of industrial and municipal membrane bioreactor (MBR) systems - lessons
      from the field.
AB  - The use of membrane bioreactors (MBRs) in activated sludge wastewater treatment
      has grown significantly in the last decade. While there is growing awareness and
      knowledge about the application of MBR technology in municipal wastewater
      treatment, not much information is available on the application of MBRs in
      industrial wastewater treatment. A comparative study of design data, operating
      conditions and the major challenges associated with MBR operations in 24 MBR
      plants treating both municipal and industrial wastewater, built by and/or
      operated by Praxair, Inc., is presented. Of the 24 MBR systems described, 12 of
      the plants used high purity oxygen (HPO). By enabling a wide range of
      food/microorganism ratios and loading conditions in the same system, HPO MBR
      systems can extend the options available to industrial plant operators to meet
      the challenges of wide fluctuations in organic loading and footprint limitations.
      While fouling in industrial MBR systems can be an issue, adequate flux and
      permeability values can be reliably maintained by the use of good maintenance
      strategies and effective process controls (pretreatment, cleaning and membrane
      autopsies). 

PMID- 25051476
TI  - Nitrogen behavior during sludge ozonation: a long-term observation by pilot
      experiments.
AB  - Sludge ozonation is a promising technology for dealing with the increasing
      challenge of excess sludge treatment and disposal. However, nitrogen behavior
      during sludge ozonation and subsequent biological removal remains unclear. To
      clarify the feasibility and stability of oxidizing organic nitrogen (released
      during sludge ozonation) in the bioreactor (but not during ozonation), and the
      best operational conditions for sludge ozonation, nitrogen behavior was
      investigated by a long-term observation. The results showed that when inlet ozone
      concentration increased from 30 to 80 mg O3/L, and ozonation time decreased from
      29 to 11 h, less soluble organic nitrogen was oxidized to ammonia (from 66.1 to
      18.7% of soluble total nitrogen). This can reduce the operational costs of sludge
      ozonation. Furthermore, it is feasible to convert organic nitrogen to nitrate by
      biological processes because full nitrification was restored in three weeks after
      shock loading of organic nitrogen owing to the change in ozonation conditions.
      After combining sludge ozonation with the anaerobic/oxic process, the mass
      balance for nitrogen showed that nitrogen in the excess sludge decreased with
      increasing sludge reduction rate. The decreased nitrogen in the excess sludge was
      mainly transformed to nitrogen gas by denitrification, whereas nitrogen in the
      effluent did not increase noticeably. 

PMID- 25051477
TI  - Modelling the viability of heat recovery from combined sewers.
AB  - Modelling of wastewater temperatures along a sewer pipe using energy balance
      equations and assuming steady-state conditions was achieved. Modelling error was
      calculated, by comparing the predicted temperature drop to measured ones in three
      combined sewers, and was found to have an overall root mean squared error of 0.37
      K. Downstream measured wastewater temperature was plotted against modelled
      values; their line gradients were found to be within the range of 0.9995-1.0012.
      The ultimate aim of the modelling is to assess the viability of recovering heat
      from sewer pipes. This is done by evaluating an appropriate location for a heat
      exchanger within a sewer network that can recover heat without impacting
      negatively on the downstream wastewater treatment plant (WWTP). Long sewers may
      prove to be more viable for heat recovery, as heat lost can be reclaimed before
      wastewater reaching the WWTP. 

PMID- 25051478
TI  - Lead removal efficiency using biosorbents as alternative materials for permeable
      reactive barriers.
AB  - As alternative materials for heavy metal removal, this study investigated
      biosorbents to determine their suitability for permeable reactive barriers. The
      lead removal efficiencies of brown seaweed (Undaria pinnatifida) and reed
      (Phragmites australis) were determined under different conditions (batch and
      column system). The experimental results for these biomaterials fitted the
      Langmuir isotherm with high correlation values. It was verified that the
      influence of temperature on affinity was higher than that on adsorption capacity.
      While the lead removal efficiency of U. pinnatifida was higher than of P.
      australis in the batch experiments, lead removal efficiency decreased for both
      materials at approximately the same time in the column experiments. This
      indicates that the dominance of the chemical and physical adsorption mechanisms
      could result in differences in these systems. 

PMID- 25051479
TI  - Microalgae harvesting and cell disruption: a preliminary evaluation of the
      technology electroflotation by alternating current.
AB  - Some species of microalgae have high productivity and lipid content, which makes
      them good candidates for biodiesel production. Biomass separation and cell
      disruption are important steps in biodiesel production from microalgae. In this
      work, we explored the fundamentals of electroflotation by alternating current
      (EFAC) with non-consumable electrodes to simultaneously harvest microalgae and
      disrupt cells from mixed microalgae obtained from waste stabilization ponds. The
      harvesting efficiency was evaluated using chlorophyll-a and turbidity, which
      reached removals of 99% and 95%, respectively, during a batch time of 140 min.
      Cell disruption was evaluated using lipid extraction, and the best results were
      achieved with a batch time of 140 min, which resulted in a 14% yield. Therefore,
      EFAC was shown to be an attractive potential technology for simultaneous
      microalgal harvesting and cell disruption. 

PMID- 25051480
TI  - Sludge accumulation in shallow maturation ponds treating UASB reactor effluent:
      results after 11 years of operation.
AB  - Polishing ponds are natural systems used for the post-treatment of upflow
      anaerobic sludge blanket (UASB) effluents. They are designed as maturation ponds
      and their main goal is the removal of pathogens and nitrogen and an additional
      removal of residual organic matter from the UASB reactor. This study aimed to
      evaluate organic matter and suspended solids removal as well as sludge
      accumulation in two shallow polishing ponds in series treating sanitary effluent
      from a UASB reactor with a population equivalent of 200 inhabitants in Brazil,
      operating since 2002. For this evaluation, long-term monitoring of biochemical
      oxygen demand and total suspended solids and bathymetric surveys have been
      undertaken. The ponds showed an irregular distribution of total solids mass in
      the sludge layer of the two ponds, with mean accumulation values of 0.020 m(3)
      person(-1) year(-1) and 0.004 m(3) person(-1) year(-1) in Ponds 1 and 2, leading
      to around 40% and 8% of the liquid volume occupied by the sediments after 11
      years of operation. The first pond showed better efficiency in relation to
      organic matter removal, although its contribution was limited, due to algal
      growth. No simple input-output mass balance of solids can be applied to the ponds
      due to algal growth in the liquid phase and sludge digestion in the sludge. 

PMID- 25051481
TI  - Application of a biofilm formed by a mixture of yeasts isolated in Vietnam to
      degrade aromatic hydrocarbon polluted wastewater collected from petroleum
      storage.
AB  - In this study, three good biofilm-forming yeast strains, including Candida
      viswanathii TH1, Candida tropicalis TH4 and Trichosporon asahii B1, were isolated
      from oil-contaminated water and sediment samples collected in coastal zones of
      Vietnam. These strains were registered in the GenBank database with the accession
      numbers JX129175, JX129176 and KC139404 for strain TH1, TH4 and B1, respectively.
      The biofilm formed by a mixture of these organisms degraded 90, 85, 82 and 67% of
      phenol, naphthalene, anthracene and pyrene, respectively, after a 7-day
      incubation period using an initial concentration of 600 ppm phenol and 200 ppm of
      each of the other compounds. In addition, this biofilm completely degraded these
      aromatic compounds, which were from wastewater collected from petroleum tanks in
      Do Xa, Hanoi after 14 days of incubation based on gas chromatography mass
      spectrometry analysis. To the best of our knowledge, reports on polycyclic
      aromatic hydrocarbon and phenol degradation by biofilm-forming yeasts are
      limited. The results obtained indicate that the biofilm formed by multiple yeast
      strains may considerably increase the degradation efficiency of aromatic
      hydrocarbon compounds, and may lead to a new approach for eliminating petroleum
      oil-contaminated water in Vietnam. 

PMID- 25051482
TI  - Improving nutrient fixation and dry matter content of an ammonium-rich anaerobic
      digestion effluent by struvite formation and clay adsorption.
AB  - The anaerobic digestion (AD) of organic wastes that contain nitrogen leads to its
      mineralization, yielding a digestate rich in ammonium (NH(4)(+)), an important
      fertilizing nutrient. The applicability of AD digestate as fertilizer can be
      improved by fixating the nutrients and increasing its dry matter content. Methods
      for the fixation and recovery of the digestate's NH(4)(+) and possible also
      PO(4)(3-) include struvite precipitation and adsorption in clay materials such as
      bentonite. These techniques were tested in batch experiments employing the liquid
      fraction of a digestate originating from the AD of a substrate mix containing
      lignocellulose, cattle manure and fish industrial waste. The concentration of
      NH(4)(+)-N in this digestate was 2,300 mg L-1. Struvite precipitation conditions
      at a molar ratio of 1.2:1:1 (Mg2+:NH(4)(+):PO(4)(3-)) and pH 9.5 were best in
      terms of simultaneous removal of NH(4)(+)-N (88%), PO(4)(3-) (60%) and soluble
      chemical oxygen demand (44%). Bentonite adsorption gave comparably high removal
      levels for NH(4)(+)-N (82%) and PO(4)(3-) (52%). Analysis of the precipitates'
      morphology and elemental composition confirmed their struvite and bentonite
      nature. Dry matter content was increased from 5.8% in the AD digestate to 27% and
      22% in the struvite and bentonite sludges, respectively.

PMID- 25051483
TI  - Coagulation pretreatment of highly concentrated acrylonitrile wastewater from
      petrochemical plants.
AB  - Acrylonitrile (AN) wastewater is a heavily polluted and a likely hazardous liquid
      that is generated during the production of AN. Several chemical methods for the
      pretreatment of AN wastewater are available in laboratory scale. However, the
      harsh reaction conditions and high operational cost make these methods
      undesirable. Until now, four-effect evaporation is the only pretreatment method
      used for AN wastewater in industry despite its huge energy consumption and high
      cost. It is difficult to find an energy-saving pretreatment technique from the
      perspective of industrial application. In this study, a safe and low-cost
      coagulation technique was developed for the pretreatment of AN wastewater. Three
      types of inorganic coagulant and three types of polymer coagulant were
      investigated for the coagulation treatment of highly concentrated AN wastewater
      from petrochemical plants. The effects of coagulant type, dosage, and coagulation
      conditions on the pretreatment efficiency of AN wastewater were investigated. The
      results show that a combination of inorganic and polymer coagulants is effective
      for the pretreatment of AN wastewater. 

PMID- 25051484
TI  - Organic matter and nitrogen removal at planted wetlands treating domestic septage
      with varying operational strategies.
AB  - A two-staged engineered wetland-based system was designed and constructed to
      treat raw domestic septage. Hydraulic loading rates (HLRs) of 8.75 and 17.5 cm/d
      were studied with four and eight daily dosings at the second stage of the system
      to investigate the influence of the regimes on septage treatment. Removal of
      organic matter (OM) was found to be HLR dependent, where the results indicated
      that the increase of HLR from 8.75 to 17.5 cm/d impaired the overall level of
      treatment in the wetland units. Effluent of wetland fed at HLR 17.5 cm/d
      presented significantly lower oxygen reduction potential and dissolved oxygen
      values than wetland fed at 8.75 cm/d, indicative of the occurrence of less
      aerobic and reductive conditions in the bed. The reoxygenation capability of the
      wetland units was found to be heavily affected by the dosing frequency especially
      under high hydraulic load (17.5 cm/d). NH3-N degradation was found to decrease
      with statistical importance when the wetland was flushed two times more
      frequently with smaller batches of influent. The number of hydraulic load
      fractionings did not seem to affect the level of treatments of OM and ammonia for
      both the wetlands fed under the lower HLR of 8.75 cm/d. Prediction of hydraulic
      limits and management of the feeding strategies are important in the vertical
      type of engineered wetlands to guarantee the treatment performance and minimize
      the chances of filter clogging. 

PMID- 25051485
TI  - Stability and sedimentation of silver nanoparticles in the presence of
      monovalent, divalent and trivalent electrolyte solutions.
AB  - The present study seeks to elucidate the effect of different electrolytes on the
      stability of citrate-coated silver nanoparticles synthesized by the reduction of
      the Ag(NH3)(2)(+) complex via Tollens' method. Time-resolved dynamic light
      scattering technique was used to measure the aggregation behavior of the
      nanoparticles over a range of electrolyte (NaCl, CaCl2, and AlCl3)
      concentrations. From the aggregation kinetic data, the critical coagulation
      concentration values were calculated as 0.11, 1.7 * 10-3, and 5.06 * 10-6 M for
      NaCl, CaCl2, and AlCl3, respectively. Supernatant of the nanoparticle suspension
      in presence of the three electrolytes was collected and measured using
      inductively coupled plasma mass spectrometry to quantify the sedimentation. It
      was found that the silver nanoparticle aggregates settled rapidly in the slow
      aggregation and fast aggregation regimes. Their sedimentation followed a
      nanoparticle size-dependent manner.

PMID- 25051486
TI  - The potential role of 'Candidatus Microthrix parvicella' in phosphorus removal
      during sludge bulking in two full-scale enhanced biological phosphorus removal
      plants.
AB  - We investigated the bacterial community compositions and phosphorus removal
      performance under sludge bulking and non-bulking conditions in two biological
      wastewater treatment systems (conventional A2/O (anaerobic/anoxic/aerobic) and
      inverted A2/O (anoxic/anaerobic/aerobic) processes) receiving the same raw
      wastewater. Sludge bulking resulted in significant shift in bacterial
      compositions from Proteobacteria dominance to Actinobacteria dominance,
      characterized by the significant presence of filamentous 'Candidatus Microthrix
      parvicella'. Quantitative real-time polymerase chain reaction (PCR) analysis
      revealed that the relative abundance of 'Candidatus Accumulibacter phosphatis', a
      key polyphosphate-accumulating organism responsible for phosphorus removal, with
      respect to 16s rRNA genes of total bacteria was 0.8 and 0.7%, respectively, for
      the conventional and inverted A2/O systems when sludge bulking occurred, which
      increased to 8.2 and 12.3% during the non-bulking period. However, the total
      phosphorus removal performance during the bulking period (2-week average: 97 +/-
      1 and 96 +/- 1%, respectively) was not adversely affected comparable to that
      during the non-bulking period (2-week average: 96 +/- 1 and 96 +/- 1%,
      respectively). Neisser staining revealed the presence of large polyphosphate
      granules in 'Candidatus Microthrix parvicella', suggesting that this microbial
      group might have been responsible for phosphorus removal during the sludge
      bulking period when 'Candidatus Accumulibacter phosphatis' was excluded from the
      systems.

PMID- 25051487
TI  - Evaluation of melioration area damage on the river Danube caused by the
      hydroelectric power plant 'Djerdap 1' backwater.
AB  - Construction of the hydroelectric power plant (HPP) 'Djerdap 1' formed a
      backwater effect on the Danube and its tributaries, which had an inevitable
      influence on groundwater level, causing it to rise and thus creating additional
      threats to all melioration areas on more than 300 km of the Danube riversides, as
      well as on the riversides of its tributaries: the Sava (100 km) and the Tisa (60
      km). In this paper, the HPP 'Djerdap 1' backwater effect on some characteristic
      melioration areas (34 in all) has been analyzed. In most of these areas intensive
      agricultural activity has always been present. An assessment of agricultural
      production damage was carried out by complex hydrodynamic calculations (60
      calculation profiles) for different backwater regimes, with the aim to precisely
      quantify the HPP 'Djerdap 1' backwater effect on groundwater piezometric levels.
      Combining them with complex agroeconomic analyses, the aim is to quantify
      agricultural production damage and to consider the perspective of melioration
      area users. This method, which combines two different, but compatible, aspects of
      the melioration area threat assessment (hydrodynamic and agroeconomic), may
      present a quality base for further agricultural production threat assessment on
      all melioration areas on the Danube riversides, with the final aim to consider
      the economic effects and the importance of its further protection. 

PMID- 25051488
TI  - Cognitive control and the anterior cingulate cortex: how conflicting stimuli
      affect attentional control in the rat.
AB  - Converging evidence supports the hypothesis that the prefrontal cortex is
      critical for cognitive control. One prefrontal subregion, the anterior cingulate
      cortex, is hypothesized to be necessary to resolve response conflicts, disregard
      salient distractors and alter behavior in response to the generation of an error.
      These situations all involve goal-oriented monitoring of performance in order to
      effectively adjust cognitive processes. Several neuropsychological disorders,
      e.g., schizophrenia, attention deficit hyperactivity and obsessive compulsive
      disorder, are accompanied by morphological changes in the anterior cingulate
      cortex. These changes are hypothesized to underlie the impairments on tasks that
      require cognitive control found in these subjects. A novel conflict monitoring
      task was used to assess the effects on cognitive control of excitotoxic lesions
      to anterior cingulate cortex in rats. Prior to surgery all subjects showed
      improved accuracy on the second of two consecutive, incongruent trials. Lesions
      to the anterior cingulate cortex abolished this. Lesioned animals had difficulty
      in adjusting cognitive control on a trial-by-trial basis regardless of whether
      cognitive changes were increased or decreased. These results support a role for
      the anterior cingulate cortex in adjustments in cognitive control. 

PMID- 25051489
TI  - A role for Na+,K+-ATPase alpha1 in regulating Rab27a localisation on melanosomes.
AB  - The mechanism(s) by which Rab GTPases are specifically recruited to distinct
      intracellular membranes remains elusive. Here we used Rab27a localisation onto
      melanosomes as a model to investigate Rab targeting. We identified the alpha1
      subunit of Na+,K+-ATPase (ATP1a1) as a novel Rab27a interacting protein in
      melanocytes and showed that this interaction is direct with the intracellular
      M4M5 loop of ATP1a1 and independent of nucleotide bound status of the Rab.
      Knockdown studies in melanocytes revealed that ATP1a1 plays an essential role in
      Rab27a-dependent melanosome transport. Specifically, expression of ATP1a1, like
      the Rab27a GDP/GTP exchange factor (Rab3GEP), is essential for targeting and
      activation of Rab27a to melanosomes. Finally, we showed that the ability of
      Rab27a mutants to target to melanosomes correlates with the efficiency of their
      interaction with ATP1a1. Altogether these studies point to a new role for ATP1a1
      as a regulator of Rab27a targeting and activation. 

PMID- 25051490
TI  - Pros and cons of ion-torrent next generation sequencing versus terminal
      restriction fragment length polymorphism T-RFLP for studying the rumen bacterial
      community.
AB  - The development of next generation sequencing has challenged the use of other
      molecular fingerprinting methods used to study microbial diversity. We analysed
      the bacterial diversity in the rumen of defaunated sheep following the
      introduction of different protozoal populations, using both next generation
      sequencing (NGS: Ion Torrent PGM) and terminal restriction fragment length
      polymorphism (T-RFLP). Although absolute number differed, there was a high
      correlation between NGS and T-RFLP in terms of richness and diversity with R
      values of 0.836 and 0.781 for richness and Shannon-Wiener index, respectively.
      Dendrograms for both datasets were also highly correlated (Mantel test = 0.742).
      Eighteen OTUs and ten genera were significantly impacted by the addition of rumen
      protozoa, with an increase in the relative abundance of Prevotella, Bacteroides
      and Ruminobacter, related to an increase in free ammonia levels in the rumen. Our
      findings suggest that classic fingerprinting methods are still valuable tools to
      study microbial diversity and structure in complex environments but that NGS
      techniques now provide cost effect alternatives that provide a far greater level
      of information on the individual members of the microbial population. 

PMID- 25051491
TI  - Evaluation of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of
      pleural tuberculosis in a high prevalence HIV/TB setting.
AB  - BACKGROUND: Diagnosis of pleural tuberculosis (TB) using routinely available
      diagnostic methods is challenging due to the paucibacillary nature of the
      disease. Histopathology and pleural tissue TB culture involves an invasive
      procedure which requires expertise and appropriate equipment, both often
      unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in
      sputum specimens but data on its performance in pleural TB is scarce. We
      evaluated the accuracy of Cepheid's Xpert MTB/Rif test on pleural fluid in the
      diagnosis of pleural TB in Uganda. METHODS: Consenting adult patients with
      exudative pleural effusions underwent pleural biopsy and the tissue obtained
      subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB
      cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also
      collected. Data on socio-demographic characteristics, clinical symptoms, HIV
      status and CD4 count were also collected. Sensitivity, specificity, positive and
      negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB
      diagnosis were calculated using pleural tissue MTB culture and/or histopathology
      as the reference standard. RESULTS: Of the 116 participants [female 50%, mean age
      34 (SD +/-13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture
      and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87
      confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test
      were 28.7% and 96.6% respectively while the positive and negative predictive
      values were 96.1% and 31.1% respectively. CONCLUSION: Xpert MTB/Rif test on
      pleural fluid does not accurately diagnose pleural TB and therefore cannot be
      used as an initial evaluation test in patients with suspected pleural TB. New,
      rapid and accurate tests for the diagnosis of pleural TB are still warranted.

PMID- 25051492
TI  - Association of IL-27 polymorphisms and cancer risk in Chinese population.
AB  - A number of genetic studies have attempted to link interleukin-27 (IL-27)
      polymorphisms (rs153109, rs17855750 and rs181206) to the risk of cancer in
      Chinese population, including glioma, ovarian cancer, hepatocellular carcinoma,
      colorectal cancer, esophageal cancer, etc. However, the results were
      inconclusive. The aim of this study is to derive a more precise estimation of any
      association in a meta-analysis. We searched the PubMed database (up to 6 June
      2014) for studies regarding the association of IL-27 polymorphisms (rs153109,
      rs17855750 and rs181206) and the risk of cancer in Chinese population. Odds
      ratios (ORs) together with their 95% confidence intervals (CIs) were calculated
      by using random/fixed effect model to assess the association. Sensitivity
      analyses were used to assess the stability of the results. Begg's test was
      performed to measure publication bias. A total of six eligible studies with 1684
      patients and 1837 controls were included in this meta-analysis. IL-27 rs153109
      polymorphism was significantly associated with cancer risk in Chinese population
      (GG versus AA: OR = 1.24, 95% CI = 1.00-1.54, p = 0.05). However, there were no
      associations between IL-27 rs17855750 and rs181206 polymorphisms and cancer risk
      in Chinese population. In conclusion, this meta-analysis indicated that IL-27
      rs153109 polymorphism was associated with cancer risk in Chinese population.

PMID- 25051493
TI  - Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with
      diabetic nephropathy risk.
AB  - Results from the published studies on the association between monocyte
      chemoattractant protein-1 (MCP-1) -2518 A/G gene polymorphism and diabetic
      nephropathy (DN) risk are still conflicting. This meta-analysis was performed to
      evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to
      explore whether MCP-1 A allele, AA genotype or GG genotype could become a
      predictive marker for DN risk. Association studies were identified from the
      databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological
      Medicine Database) as of 1 March 2014, and eligible investigations were
      synthesized using meta-analysis method. Four studies were identified for the
      analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all
      the included studies were form Asian population. The association between MCP-1
      A/G gene polymorphism and DN susceptibility was not found (A allele: OR = 1.19;
      95% CI: 0.97-1.45; p = 0.10; AA genotype: OR = 1.27; 95% CI: 0.95-1.70; p = 0.11;
      GG genotype: OR = 0.77; 95% CI: 0.57-1.05; p = 0.10). In the sensitive analysis,
      according to the control source from hospital, we found that AA genotype was
      associated with the DN risk (OR = 1.45; 95% CI: 1.05-2.00; p = 0.02). However,
      other associations were not found in the sensitive analysis according to the
      control source from hospital or population. Our results indicate that AA
      homozygous might be a significant genetic molecular marker to predict the
      diabetes mellitus patients developing into DN. However, more investigations are
      required to further clarify this association.

PMID- 25051494
TI  - Association of vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI
      (rs731236) and ApaI (rs7975232) gene polymorphism with the nephrolithiasis
      susceptibility.
AB  - Association of vitamin D receptor (VDR) gene polymorphism with the risk of
      nephrolithiasis from the published reports is still conflicting. This study was
      conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1
      (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk
      of nephrolithiasis using meta-analysis method. The association studies were
      identified from PubMed, and Cochrane Library on 1 April 2014, and eligible
      investigations were included and synthesized using meta-analysis method. Six
      reports were recruited into this meta-analysis for the association of VDR BsmI,
      Fok1, TaqI and ApaI gene polymorphism with nephrolithiasis susceptibility. In
      this meta-analysis, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not
      associated with nephrolithiasis susceptibility for overall populations and in
      Caucasians. However, the Fok1 f allele and ff genotype were associated with the
      risk of nephrolithiasis in Asians, but the FF genotype not. Furthermore, TaqI TT
      genotype was associated with the risk of nephrolithiasis in Asians, but the t
      allele and tt genotype not. However, ApaI gene polymorphism was not associated
      with nephrolithiasis susceptibility in Asians. In conclusion, VDR BsmI, Fok1,
      TaqI and ApaI gene polymorphism were not associated with nephrolithiasis risk in
      overall populations and in Caucasians. But, the Fok1 f allele and ff genotype,
      TaqI TT genotype, ApaI gene polymorphism were associated with the risk of
      nephrolithiasis in Asians. However, more studies should be conducted to confirm
      it. 

PMID- 25051495
TI  - Uterine pathology in women undergoing minimally invasive hysterectomy using
      morcellation.

PMID- 25051496
TI  - FRET-assisted determination of CLN3 membrane topology.
AB  - Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3
      gene, which encodes for a putative lysosomal transmembrane protein with thus far
      undescribed structure and function. Here we investigate the membrane topology of
      human CLN3 protein with a combination of advanced molecular cloning,
      spectroscopy, and in silico computation. Using the transposomics cloning method
      we first created a library of human CLN3 cDNA clones either with a randomly
      inserted eGFP, a myc-tag, or both. The functionality of the clones was evaluated
      by assessing their ability to revert a previously reported lysosomal phenotype in
      immortalized cerebellar granular cells derived from Cln3Deltaex7/8 mice
      (CbCln3Deltaex7/8). The double-tagged clones were expressed in HeLa cells, and
      FRET was measured between the donor eGFP and an acceptor DyLight547 coupled to a
      monoclonal alpha-myc antibody to assess their relative membrane orientation. The
      data were used together with previously reported experimental data to compile a
      constrained membrane topology model for hCLN3 using TOPCONS consensus membrane
      prediction algorithm. Our model with six transmembrane domains and cytosolic N-
      and C-termini largely agrees with those previously suggested but differs in terms
      of the transmembrane domain positions as well as in the size of the luminal
      loops. This finding improves understanding the function of the native hCLN3
      protein. 

PMID- 25051497
TI  - Noncoding RNAs in vascular inflammation and atherosclerosis: recent advances
      toward therapeutic applications.
AB  - PURPOSE OF REVIEW: We here highlight recent studies that in vivo demonstrate an
      involvement of microRNAs in atherosclerotic lesion formation and provide
      important preclinical evidence of their therapeutic targeting in atherosclerosis,
      with a particular focus on endothelial cells and macrophages. We also briefly
      discuss the emerging role of long noncoding RNAs herein. RECENT FINDINGS:
      Noncoding RNAs have received considerable attention as regulators of different
      cell types and functions that dictate the inflammatory response in
      atherosclerosis. In particular, microRNAs have emerged to control endothelial
      cell functions by acting as mechanosensors that are regulated by flow,
      determinants of inflammation in the context of cytokine exposure and
      hypercholesterolemia and guardians of endothelial homeostasis. In addition,
      microRNAs control macrophage-driven cytokine production and polarization, and
      regulate cholesterol metabolism and foam cell formation. By these (cell specific)
      effects, microRNAs contain or drive atherosclerotic lesion formation and
      progression in animal models of disease and can be harnessed for therapeutic
      targeting. SUMMARY: Given their multifaceted and specific contribution to
      vascular inflammation and atherosclerosis, and proven amenability for successful
      modulation in preclinical murine models of atheroscleorosis and large animal
      studies, miRNAs appear as promising therapeutic targets for treating
      atherosclerosis.

PMID- 25051498
TI  - Identification of proteins associated with an IFNgamma-responsive promoter by a
      retroviral expression system for enChIP using CRISPR.
AB  - Isolation of specific genomic regions retaining molecular interactions is
      essential for comprehensive identification of molecules associated with the
      genomic regions. Recently, we developed the engineered DNA-binding molecule
      mediated chromatin immunoprecipitation (enChIP) technology for purification of
      specific genomic regions. Here, we developed a retroviral expression system for
      enChIP using CRISPR. We showed that the target genomic locus can be purified with
      high efficiency by using this system. We also showed that contamination of
      potential off-target sites is negligible by using this system if the guide RNA
      (gRNA) for the target site has a sufficiently long unique sequence in its seed
      sequence. enChIP combined with stable isotope labeling using amino acids in cell
      culture (SILAC) analysis identified proteins whose association with the
      interferon (IFN) regulatory factor-1 (IRF-1) promoter region increases in
      response to IFNgamma stimulation. The list of the associated proteins contained
      many novel proteins in the context of IFNgamma-induced gene expression as well as
      proteins related to histone deacetylase complexes whose involvement has been
      suggested in IFNgamma-mediated gene expression. Finally, we confirmed IFNgamma
      induced increased association of the identified proteins with the IRF-1 promoter
      by ChIP. Thus, our results showed that the retroviral enChIP system using CRISPR
      would be useful for biochemical analysis of genome functions including
      transcription and epigenetic regulation. 

PMID- 25051499
TI  - Cultural background influences implicit but not explicit sense of agency for the
      production of musical tones.
AB  - The sense of agency is suggested to occur at both low and high levels by the
      involvement of sensorimotor processes and the contribution of retrospective
      inferences based on contextual cues. In the current study, we recruited western
      and non-western participants and examined the effect of pleasantness of action
      outcomes on both feeling of control ratings and intentional binding which refers
      to the perceived compression of the temporal delay between actions and outcomes.
      We found that both western and non-western groups showed greater feeling of
      control ratings for the consonant (pleasant) compared to dissonant (unpleasant)
      outcomes. The intentional binding effect, on the other hand, was stronger for the
      consonant compared to dissonant outcomes in the western group only. We discuss
      the results in relation to how cultural background might differentially influence
      the effect of outcome pleasantness on low and high levels of the sense of agency.

PMID- 25051500
TI  - Carboxypeptidase E modulates intestinal immune homeostasis and protects against
      experimental colitis in mice.
AB  - Enteroendocrine cells (EEC) produce neuropeptides, which are crucially involved
      in the maintenance of the intestinal barrier. Hence, EEC dysfunction is suggested
      to be involved in the complex pathophysiology of inflammatory bowel disease
      (IBD), which is characterized by decreased intestinal barrier function. However,
      the underlying mechanisms for EEC dysfunction are not clear and suitable models
      for a better understanding are lacking. Here, we demonstrate that
      Carboxypeptidase E (CPE) is specifically expressed in EEC of the murine colon and
      ileum and that its deficiency is associated with reduced intestinal levels of
      Neuropeptide Y (NPY) and Peptide YY (PYY), which are both produced by EEC.
      Moreover, cpe-/- mice exhibit an aggravated course of DSS-induced chronic colitis
      compared to wildtype littermates. In addition, we observed elevated mucosal IL-6
      and KC transcript levels already at baseline conditions in cpe-/- mice. Moreover,
      supernatants obtained from isolated intestinal crypts of cpe-/- mice lead to
      increased IL-6 and KC expression in MODE-K cells in the presence of LPS. This
      effect was reversible by co-administration of recombinant NPY, suggesting a CPE
      mediated immunosuppressive effect in the intestines by influencing the processing
      of specific neuropeptides. In this context, the chemotaxis of bone marrow derived
      macrophages towards respective supernatants was enhanced. In conclusion, our data
      point to an anti-inflammatory role of CPE in the intestine by influencing local
      cytokine levels and thus regulating the migration of myeloid immune cells into
      the mucosa. These findings highlight the importance of EEC for intestinal
      homeostasis and propose EEC as potential therapeutic targets in IBD. 

PMID- 25051502
TI  - Unconventional secretion of fibroblast growth factor 2--a novel type of protein
      translocation across membranes?
AB  - N-terminal signal peptides are a hallmark of the vast majority of soluble
      secretory proteins that are transported along the endoplasmic reticulum/Golgi
      dependent pathway. They are recognized by signal recognition particle, a process
      that initiates membrane translocation into the lumen of the endoplasmic reticulum
      followed by vesicular transport to the cell surface and release into the
      extracellular space. Beyond this well-established mechanism of protein secretion
      from eukaryotic cells, a number of extracellular proteins with critical
      physiological functions in immune surveillance and tissue organization are known
      to be secreted in a manner independent of signal recognition particle. Such
      processes have collectively been termed "unconventional protein secretion" and,
      while known for more than two decades, their underlying mechanisms are only
      beginning to emerge. Different types of unconventional secretory mechanisms have
      been described with the best-characterized example being based on direct
      translocation of cytoplasmic proteins across plasma membranes. The aim of this
      review is to critically assess our current knowledge of this type of
      unconventional secretion focusing on fibroblast growth factor 2 (FGF2) as the
      most established example. 

PMID- 25051501
TI  - Mortality after parental death in childhood: a nationwide cohort study from three
      Nordic countries.
AB  - BACKGROUND: Bereavement by spousal death and child death in adulthood has been
      shown to lead to an increased risk of mortality. Maternal death in infancy or
      parental death in early childhood may have an impact on mortality but evidence
      has been limited to short-term or selected causes of death. Little is known about
      long-term or cause-specific mortality after parental death in childhood. METHODS
      AND FINDINGS: This cohort study included all persons born in Denmark from 1968 to
      2008 (n = 2,789,807) and in Sweden from 1973 to 2006 (n = 3,380,301), and a
      random sample of 89.3% of all born in Finland from 1987 to 2007 (n = 1,131,905).
      A total of 189,094 persons were included in the exposed cohort when they lost a
      parent before 18 years old. Log-linear Poisson regression was used to estimate
      mortality rate ratio (MRR). Parental death was associated with a 50% increased
      all-cause mortality (MRR = 1.50, 95% CI 1.43-1.58). The risks were increased for
      most specific cause groups and the highest MRRs were observed when the cause of
      child death and the cause of parental death were in the same category. Parental
      unnatural death was associated with a higher mortality risk (MRR = 1.84, 95% CI
      1.71-2.00) than parental natural death (MRR = 1.33, 95% CI 1.24-1.41). The
      magnitude of the associations varied according to type of death and age at
      bereavement over different follow-up periods. The main limitation of the study is
      the lack of data on post-bereavement information on the quality of the parent
      child relationship, lifestyles, and common physical environment. CONCLUSIONS:
      Parental death in childhood or adolescence is associated with increased all-cause
      mortality into early adulthood. Since an increased mortality reflects both
      genetic susceptibility and long-term impacts of parental death on health and
      social well-being, our findings have implications in clinical responses and
      public health strategies. Please see later in the article for the Editors'
      Summary.

PMID- 25051503
TI  - Enhancing the hole-conductivity of spiro-OMeTAD without oxygen or lithium salts
      by using spiro(TFSI)2 in perovskite and dye-sensitized solar cells.
AB  - 2,2',7,7'-Tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro
      OMeTAD), the prevalent organic hole transport material used in solid-state dye
      sensitized solar cells and perovskite-absorber solar cells, relies on an
      uncontrolled oxidative process to reach appreciable conductivity. This work
      presents the use of a dicationic salt of spiro-OMeTAD, named spiro(TFSI)2, as a
      facile means of controllably increasing the conductivity of spiro-OMeTAD up to
      10(-3) S cm(-1) without relying on oxidation in air. Spiro(TFSI)2 enables the
      first demonstration of solid-state dye-sensitized solar cells fabricated and
      operated with the complete exclusion of oxygen after deposition of the sensitizer
      with higher and more reproducible device performance. Perovskite-absorber solar
      cells fabricated with spiro(TFSI)2 show improved operating stability in an inert
      atmosphere. Gaining control of the conductivity of the HTM in both dye-sensitized
      and perovskite-absorber solar cells in an inert atmosphere using spiro(TFSI)2 is
      an important step toward the commercialization of these technologies. 

PMID- 25051504
TI  - Comparative gene and protein expression analyses of a panel of cytokines in acute
      and chronic drug-induced liver injury in rats.
AB  - Drug-induced liver injury (DILI) is a significant safety issue associated with
      medication use, and is the major cause of failures in drug development and
      withdrawal in post marketing. Cytokines are signaling molecules produced and
      secreted by immune cells and play crucial roles in the progression of DILI.
      Although there are numerous reports of cytokine changes in several DILI models, a
      comprehensive analysis of cytokine expression changes in rat liver injury induced
      by various compounds has, to the best of our knowledge, not been performed. In
      the past several years, we have built a public, free, large-scale toxicogenomics
      database, called Open TG-GATEs, containing microarray data and toxicity data of
      the liver of rats treated with various hepatotoxic compounds. In this study, we
      measured the protein expression levels of a panel of 24 cytokines in frozen liver
      of rats treated with a total of 20 compounds, obtained in the original study that
      formed the basis of the Open TG-GATEs database and analyzed protein expression
      profiles combined with mRNA expression profiles to investigate the correlation
      between mRNA and protein expression levels. As a result, we demonstrated
      significant correlations between mRNA and protein expression changes for
      interleukin (IL)-1beta, IL-1alpha, monocyte chemo-attractant protein (MCP)-1/CC
      chemokine ligand (Ccl)2, vascular endothelial growth factor A (VEGF-A), and
      regulated upon activation normal T cell expressed and secreted (RANTES)/Ccl5 in
      several different types of DILI. We also demonstrated that IL-1beta protein and
      MCP-1/Ccl2 mRNA were commonly up-regulated in the liver of rats treated with
      different classes of hepatotoxicants and exhibited the highest accuracy in the
      detection of hepatotoxicity. The results also demonstrate that hepatic mRNA
      changes do not always correlate with protein changes of cytokines in the liver.
      This is the first study to provide a comprehensive analysis of mRNA-protein
      correlations of factors involved in various types of DILI, as well as additional
      insights into the importance of understanding complex cytokine expression changes
      in assessing DILI. 

PMID- 25051505
TI  - Bio-inspired multistructured conical copper wires for highly efficient liquid
      manipulation.
AB  - Animal hairs are typical structured conical fibers ubiquitous in natural system
      that enable the manipulation of low viscosity liquid in a well-controlled manner,
      which serves as the fundamental structure in Chinese brush for ink delivery in a
      controllable manner. Here, drawing inspiration from these structure, we developed
      a dynamic electrochemical method that enables fabricating the anisotropic
      multiscale structured conical copper wire (SCCW) with controllable conicity and
      surface morphology. The as-prepared SCCW exhibits a unique ability for
      manipulating liquid with significantly high efficiency, and over 428 times
      greater than its own volume of liquid could be therefore operated. We propose
      that the boundary condition of the dynamic liquid balance behavior on conical
      fibers, namely, steady holding of liquid droplet at the tip region of the SCCW,
      makes it an excellent fibrous medium to manipulate liquid. Moreover, we
      demonstrate that the titling angle of the SCCW can also affect its efficiency of
      liquid manipulation by virtue of its mechanical rigidity, which is hardly
      realized by flexible natural hairs. We envision that the bio-inspired SCCW could
      give inspiration in designing materials and devices to manipulate liquid in a
      more controllable way and with high efficiency. 

PMID- 25051509
TI  - Altered attention for stimuli on the hands.
AB  - Attention operates in the space near the hands with unique, action-related
      priorities. Here, we examined how attention treats objects on the hands
      themselves. We tested two hypotheses. First, attention may treat stimuli on the
      hands like stimuli near the hands, as though the surface of the hands were the
      proximal case of near-hand space. Alternatively, we proposed that the surface of
      the hands may be attentionally distinct from the surrounding space. Specifically,
      we predicted that attention should be slow to orient toward the hands in order to
      remain entrained to near-hand space, where the targets of actions are usually
      located. In four experiments, we observed delayed orienting of attention on the
      hands compared to orienting attention near or far from the hands. Similar delayed
      orienting was also found for tools connected to the body compared to tools
      disconnected from the body. These results support our second hypothesis:
      attention operates differently on the functional surfaces of the hand. We suggest
      this effect serves a functional role in the execution of manual actions. 

PMID- 25051510
TI  - Synthesis and luminescent properties of La(1-x)Nd(x)P5O14 nanocrystals.
AB  - La(1-x)Nd(x)P5O14 nanocrystals were synthesized using a coprecipitation method.
      Their structure and morphology were determined. The luminescence and excitation
      spectra of La(1-x)Nd(x)P5O14 nanocrystals were measured in the entire range of
      Nd(3+) concentration. It was found that the relative intensities of absorption
      transitions increased significantly with concentration due to the cooperative
      interactions. The effect of concentration on fluorescence transitions was
      investigated. It was found that the intensity of the (4)F3/2 -> (4)I11/2
      transition significantly increased with concentration relative to the resonant
      (4)F3/2 -> (4)I9/2 transition almost three times due to strong reabsorption. The
      concentration quenching of fluorescence was discussed in terms of the Yokota
      Tanimoto model.

PMID- 25051508
TI  - Scientists' views about attribution of global warming.
AB  - Results are presented from a survey held among 1868 scientists studying various
      aspects of climate change, including physical climate, climate impacts, and
      mitigation. The survey was unique in its size, broadness and level of detail.
      Consistent with other research, we found that, as the level of expertise in
      climate science grew, so too did the level of agreement on anthropogenic
      causation. 90% of respondents with more than 10 climate-related peer-reviewed
      publications (about half of all respondents), explicitly agreed with
      anthropogenic greenhouse gases (GHGs) being the dominant driver of recent global
      warming. The respondents' quantitative estimate of the GHG contribution appeared
      to strongly depend on their judgment or knowledge of the cooling effect of
      aerosols. The phrasing of the IPCC attribution statement in its fourth assessment
      report (AR4)-providing a lower limit for the isolated GHG contribution-may have
      led to an underestimation of the GHG influence on recent warming. The phrasing
      was improved in AR5. We also report on the respondents' views on other factors
      contributing to global warming; of these Land Use and Land Cover Change (LULCC)
      was considered the most important. Respondents who characterized human influence
      on climate as insignificant, reported having had the most frequent media coverage
      regarding their views on climate change. 

PMID- 25051506
TI  - Combined effect of nerve growth factor and brain-derived neurotrophic factor on
      neuronal differentiation of neural stem cells and the potential molecular
      mechanisms.
AB  - Neural stem cells (NSCs) are important pluripotent stem cells, which have
      potential applications in cell replacement therapy. Brain-derived neurotrophic
      factor (BDNF) and nerve growth factor (NGF) have been demonstrated to exert a
      marked impact on the proliferation and differentiation of NSCs. The effects of
      NGF, BDNF, and BDNF combined with NGF on NSC neuronal differentiation and the
      possible mechanisms for these effects were investigated in this study. An
      adherent monolayer culture was employed to obtain highly homogeneous NSCs. The
      cells were divided into four groups: Control, NGF, BDNF and combination (BDNF +
      NGF) groups. Neuron differentiation was examined using immunocytochemistry and
      phospho-extracellular signal-regulated kinase (p-ERK) levels were analyzed using
      western blotting. Reverse transcription polymerase chain reaction was used to
      measure the mRNA expression levels of the HES1, HES5, MASH1, NGN1 and NeuroD
      transcription factors at different time intervals following neurotrophin-induced
      differentiation. NGF and BDNF were observed to induce NSC neuronal
      differentiation, and beta-tubulin III-positive cells and p-ERK expression levels
      were highest in the NGF + BDNF combination group at all time points. The
      proportion of beta-tubulin III-positive neurons in each group was associated with
      the expression levels of MASH1, NGN1 and NeuroD in the group. In conclusion, BDNF
      combined with NGF significantly improved NSC neuronal differentiation, which may
      provide support for the practical application of NSCs in neurodegenerative
      diseases.

PMID- 25051511
TI  - Celiac Disease: Ten Things That Every Gastroenterologist Should Know.
AB  - There are 10 things that all gastroenterologists should know about celiac disease
      (CD). (1) The immunoglobulin A tissue transglutaminase is the single best
      serologic test to use for the detection of CD. (2) CD can be recognized
      endoscopically, and water immersion enhances villi detection, although a normal
      endoscopic appearance does not preclude the diagnosis. (3) It is recommended that
      4 biopsies be taken from the second part of the duodenum and 2 bulb biopsies be
      taken at the 9 o'clock and 12 o'clock positions to maximize the sensitivity for
      histologic confirmation of CD. (4) Consider serologic testing of first-degree
      relatives, patients with type 1 diabetes mellitus, Down's, Turner's, and
      Williams' syndromes, as well as those with premature osteoporosis, iron
      deficiency, abnormal liver biochemistries, and other manifestations of CD. (5)
      Patients already on a prolonged gluten-free diet (GFD) should be tested for the
      presence of HLA DQ2 or DQ8, thereby avoiding the need for further evaluation of
      CD in non-allelic carriers. (6) The basic treatment of CD is a strict, lifelong
      GFD, enabled by an expert dietitian. (7) Newly diagnosed adults with CD should be
      assessed for micronutrient deficiencies (iron, B12, folate, zinc, copper), fat
      soluble vitamin deficiencies (vitamin D), and bone densitometry. (8) All patients
      diagnosed with CD should have clinical follow-up to ensure response and adherence
      to a GFD. (9) In those with persistent or relapsing symptoms, the robustness of
      the original diagnosis should be reviewed, gluten exposure sought, and a
      systematic evaluation for alternative and associated diseases performed. (10)
      Evaluate those with refractory disease for malignant transformation. 

PMID- 25051512
TI  - Palatal ulcer as an initial manifestation of Crohn's disease.

PMID- 25051513
TI  - Incidental subepithelial sigmoid colon lesion.

PMID- 25051514
TI  - Total myrosinase activity estimates in brassica vegetable produce.
AB  - Isothiocyanates, generated from the hydrolysis of glucosinolates in plants of the
      Brassicaceae family, promote health, including anticancer bioactivity. Hydrolysis
      requires the plant enzyme myrosinase, giving myrosinase a key role in health
      promotion by brassica vegetables. Myrosinase measurement typically involves
      isolating crude protein, potentially underestimating activity in whole foods.
      Myrosinase activity was estimated using unextracted fresh tissues of five
      broccoli and three kale cultivars, measuring the formation of allyl
      isothiocyanate (AITC) and/or glucose from exogenous sinigrin. A correlation
      between AITC and glucose formation was found, although activity was substantially
      lower measured as glucose release. Using exogenous sinigrin or endogenous
      glucoraphanin, concentrations of the hydrolysis products AITC and sulforaphane
      correlated (r = 0.859; p = 0.006), suggesting that broccoli shows no myrosinase
      selectivity among sinigrin and glucoraphanin. Measurement of AITC formation
      provides a novel, reliable estimation of myrosinase-dependent isothiocyanate
      formation suitable for use with whole vegetable food samples. 

PMID- 25051515
TI  - Studies on the in vitro cultivation of ciliate protozoa from the kangaroo
      forestomach.
AB  - The methods used for culturing rumen protozoa were found to be unsatisfactory for
      growth of ciliate protozoa from the kangaroo forestomach. Based on published
      measurements of physical parameters in the marsupial forestomach, several
      modifications were incorporated into the procedure, i.e., an increase in %
      hydrogen in the gas phase, adjustment of initial pH of the medium to 6.9-7.0
      range, feed only forage as a substrate and incubate at a lower temperature (33-36
      degrees C). Only incubation at the lower temperature increased survival time of
      the kangaroo protozoa. Two species of Bitricha were still viable after 28 d in
      culture. Cultures had to be terminated at that time. One of the species differed
      considerably in size and shape from previously described species and based on 18S
      rRNA data, may represent a new species of Bitricha. The second species, present
      in low numbers was identified as Bitricha oblata. In a separate trial,
      Macropodinium yalanbense survived for 11 d, at which time these cultures also had
      to be terminated.

PMID- 25051516
TI  - Improved description of the bipolar ciliate, Euplotes petzi, and definition of
      its basal position in the Euplotes phylogenetic tree.
AB  - Data improving the characterization of the marine Euplotes species, E. petzi
      Wilbert and Song, 2008, were obtained from morphological, ecological and genetic
      analyses of Antarctic and Arctic wild-type strains. This species is identified by
      a minute (mean size, 46 MUm * 32 MUm) and ellipsoidal cell body which is dorsally
      decorated with an argyrome of the double-patella type, five dorsal kineties (of
      which the median one contains 8-10 dikinetids), five sharp-edged longitudinal
      ridges, and a right anterior spur. Ventrally, it bears 10 fronto-ventral, five
      transverse, two caudal and two marginal cirri, 30-35 adoral membranelles, and
      three inconspicuous ridges. Euplotes petzi grows well at 4  degrees C on green
      algae, does not produce cysts, undergoes mating under the genetic control of a
      multiple mating-type system, constitutively secretes water-borne pheromones, and
      behaves as a psychrophilic microorganism unable to survive at >15  degrees C.
      While the alpha-tubulin gene sequence determination did not provide useful
      information on the E. petzi molecular phylogeny, the small subunit rRNA (SSU
      rRNA) gene sequence determination provided solid evidence that E. petzi clusters
      with E. sinicus Jiang et al., 2010a, into a clade which represents the deepest
      branch at the base of the Euplotes phylogentic tree.

PMID- 25051517
TI  - Stephanoeca arndti spec. nov.--first cultivation success including molecular and
      autecological data from a freshwater acanthoecid choanoflagellate from Samoa.
AB  - Until recently acanthoecid choanoflagellates have been described only from marine
      and brackish waters. Here I describe a distinct, strictly freshwater acanthoecid
      species from Samoa based on its morphology, ecology and molecular biological data
      (partial Small Subunit rDNA). The lorica of the species is characterised by two
      extensions at the posterior chamber which are used for attachment to the
      substratum. The posterior chamber is constructed of irregularly arranged costae.
      The anterior chamber consists of four transverse costal rings and 14-18
      longitudinal costae. Despite its sturdy appearance, the lorica was extremely
      sensitive to water turbulence and movements of the water. The species showed a
      salinity tolerance of 0.5 practical salinity units with reduced growth rates and
      a temperature tolerance range of 20-34  degrees C. According to the morphology,
      phylogenetic analysis, and autecology of the species it was classified as a
      member of the genus Stephanoeca.

PMID- 25051518
TI  - Biphasic presence of fibrocytes in a porcine hypertrophic scar model.
AB  - The duroc pig has been described as a promising animal model for use in the study
      of human wound healing and scar formation. However, little is known about the
      presence and chronology of the fibrocyte cell population in the healing process
      of these animals. Wounds known to form scar were created on red duroc swine (3" x
      3") with a dermatome to a total depth of either 0.06 inches or 0.09 inches. These
      wounds were allowed to heal completely and biopsies were done at scheduled time
      points during the healing process. Biopsies were formalin fixed and paraffin
      embedded for immunohistochemical analysis. Porcine reactive antibodies to CD-45
      and procollagen-1 and a human reactive antibody to LSP-1 were used to detect the
      presence of fibrocytes in immunohistochemistry, an immunocytochemistry. Initial
      immunohistochemical studies showed evidence of a biphasic presence of fibrocytes.
      Pigs with 0.06 inches deep wounds showed positive staining for CD-45 and LSP-1
      within highly cellular areas at days 2 and 4 after wounding. Additional animals
      with 0.09 inches deep wounds showed positive staining within similar areas at
      days 56, 70, and 113 after wounding. There was no immunohistochemical evidence of
      fibrocytes in skin biopsies taken at days 14, 28, or 42. Procollagen-1 staining
      was diffused in all samples. Cultured cells were stained for CD-45, LSP-1, and
      procollagen-1 by immunocytochemistry. These data confirm that fibrocytes are
      indeed present in this porcine model. We conclude that these cells are present
      after initial wounding and later during scar formation and remodeling. We believe
      that this is an evidence of a biphasic presence of fibrocytes, first as an acute
      response to skin wounding followed by later involvement in the remodeling
      process, prompted by continued inflammation in a deep partial thickness wound. 

PMID- 25051519
TI  - Clinical and psychiatric characteristics of self-inflicted burn patients in the
      United States: comparison with a nonintentional burn group.
AB  - The main objective of the present study was to examine whether self-inflicted
      burn patients would differ from nonintentional, nonwork related burn patients on
      psychiatric and personality characteristics. Sociodemographic and injury related
      factors were also compared. Self-inflicted (N = 15) and nonintentional (N = 178)
      burn patient samples were drawn from a larger study examining physical and
      psychosocial outcomes following major burn. Psychiatric/personality factors
      included self-reported psychiatric treatment history, alcohol/drug use, preburn
      mental health (Short Form Health Survey-12 MCS) and neuroticism (NEO five factor
      inventory). Sociodemographic factors and injury related factors were obtained
      through medical records. Comparisons between the self-inflicted and the
      nonintentional groups were made using Fisher's exact tests for categorical
      variables and Wilcoxon rank-sum tests for continuous variables. The self
      inflicted group was 11.5 times more likely to report prior psychiatric treatment
      relative to the nonintentional burn group (P < .001) and 4.3 times more likely to
      have previously abused alcohol (P = .02). Compared to nonintentional burn
      patients, self-inflicted burn patients reported worse preburn mental health (P <
      .001). There were no differences on TBSA (P = .52) or sociodemographic
      characteristics (P values > .08). Relative to survivors of nonintentional burns,
      self-inflicted burn patients in the United States demonstrate high psychiatric
      comorbidity. Standards of care must be developed to optimize treatment procedures
      and recovery outcomes in this subgroup. 

PMID- 25051520
TI  - Fibrocytes participate in the development of heterotopic ossification.
AB  - Heterotopic ossification (HO) is a complication of musculoskeletal injury
      characterized by the formation of mature bone in soft tissues. The etiology of HO
      is unknown. We investigated the role of bone marrow derived progenitor cells in
      HO pathophysiology. We isolated the cells from HO specimens by cell explantation.
      Using flow cytometry and immunofluorescence microscopy, we found that 35 to 65%
      of the HO cells exhibit a bone marrow derived fibrocyte profile consisting in
      spindle-shaped morphology associated with type 1 pro-collagen and LSP1
      expression. When cultured in osteogenic differentiation medium, active machinery
      for bone mineralization (high gene expression of Anx2, TNAP, and Pit-1), and
      calcium/phosphate deposits were found. Interestingly, interferon-alpha 2b
      significantly reduced the proliferation rate and COL1 gene expression in HO
      cells. We have characterized a novel subset of bone marrow derived progenitor
      cells in the HO specimens. The findings from this research study will provide new
      insights into the development of HO in burn patients. 

PMID- 25051521
TI  - A systematic review on burn scar contracture treatment: searching for evidence.
AB  - Treating burn scar contracture remains a challenging problem for reconstructive
      surgeons. At present, no consensus exists on when to use what kind of technique.
      Therefore, a systematic review was performed on the effectiveness of the
      different surgical techniques after burn scar contracture release. Electronic
      databases were searched using a predefined search strategy. Studies evaluating
      the outcome of surgical techniques for the treatment of burn scar contractures
      were included. The methodological quality was tested and the data were
      summarized. One thousand six hundred fourty-nine papers were identified of which
      17 met the inclusion criteria. Three papers reported on a controlled trial, 14
      were cohort studies, including 10 of a pre-post operative design and 4 of a
      comparative design. The papers described outcomes of grafts, flaps with random or
      defined vascularization, and dermal substitutes. All studies had methodological
      shortcomings and most used inappropriate statistical methods. The current
      evidence on the effectiveness of reconstruction techniques for burn scar
      contractures was summarized. Due to the scarcity and low quality of the included
      studies, no definitive conclusions could be reached about the effectiveness of
      different techniques. Therefore, no direct implications for daily practice could
      be made. However, recommendations could be given for improvement of the quality
      of further primary research on the effectiveness of surgical treatment strategies
      for burn scar contracture release. 

PMID- 25051522
TI  - Pyoderma gangrenosum: a difficult diagnosis best managed in a burn treatment
      center.
AB  - Pyoderma gangrenosum (PG) is a rare immunological disorder with inexplicable
      white blood cell infiltration into the epidermis with necrosis and excruciating
      pain. Diagnosis is by exclusion which delays proper treatment. Surgical
      intervention often exacerbates wounds. Between 2004 and 2010, seven patients with
      PG were admitted to our burn treatment center (BTC). Multiple treatment
      modalities were used on these patients. An institutional review board-approved
      retrospective study investigated seven PG BTC admissions. Demographic
      information, symptom onset, time to diagnosis, admission or transfer, length of
      stay (LOS), use of corticosteroids, and prior surgery were collected. The average
      time to PG diagnosis was 18.7 days and the average wound surface area was 3.9%.
      The average patient age was 64.6 years (median 66 years) and there were five men
      and two women patients. The average symptom onset was 70.5 days prior to BTC
      admission. The BTC wound care lasted 24 days. Six of the seven patients had lower
      extremity lesions vs one with lesions involving the abdomen. Inflammatory bowel
      disease was noted in two patients, one with malignant melanoma, and another with
      psoriasis. Corticosteroids were begun 1.75 days after admission for six of the
      seven patients. Of the seven PG patients, five had excision and/or skin grafting
      with vacuum-assisted wound closure used in four. Six patients were discharged,
      but one patient succumbed early to sepsis. Skin grafting often speeds up chronic
      wound closure; however for PG this causes progression of lesions. Persistent non
      healing wounds with pain disproportionate to size may be PG. Prompt diagnosis and
      BTC specialized care greatly improve outcomes for PG patients. 

PMID- 25051524
TI  - Volumetric measurements by image segmentation on centrifugal microfluidic
      platforms in motion.
AB  - An image segmentation based method was developed to perform volumetric
      measurements of liquid aliquots in centrifugal microfluidic platforms in motion.
      The method was designed to be as automated as possible to allow its applicability
      to the large variety of available design features that tend to be included on
      such platforms. Experiments have indicated a relative standard deviation (RSD) of
      0.3% for replicate measurements and 1% for same volume aliquots injected into
      different sized chambers. The versatility of the method in regards to chamber
      shape and size, liquid colour and platform rotational frequency was demonstrated.
      This flexibility should allow it to be used for a variety of applications
      including real time metering of volumes in platforms, quantitative monitoring of
      a design's performance in real time and could result in the elimination of
      metering chambers for some applications. 

PMID- 25051523
TI  - Skin allograft and vascularized composite allograft: potential for long-term
      efficacy in the context of lymphatic modulation.
AB  - Tissue transplantation restores form and function in burn patients. The treatment
      of burn injuries is influenced by severity, location, and the percentage of total
      body surface area. There have been a number of different techniques developed to
      temporize and repair the destroyed tissue. However, in patients with large wound
      burden, sufficient donor site tissue may not be available for autograft
      harvesting. Such extensive burns necessitate other temporary and permanent
      options for wound coverage such as skin or vascularized composite allografts
      (VCA). Rejection of these tissues presents an ongoing problem which is currently
      managed using a host of systemic immunosuppressive medications. This article
      discusses the mechanism behind the innate and adaptive immune systems rejection
      of the allografts. By understanding these pathways, various techniques using
      immunomodulatory protocols have led to increased allograft survival. However, our
      primary interest lies in the initial recognition of the graft. We tailor this
      article to have a specific emphasis on lymphatic modulation as a potential
      adjunctive therapy. Reviews of the studies evaluating the effect of lymph node
      modulation on graft survival are described with future implications to allograft
      transplant research. 

PMID- 25051525
TI  - Subwavelength focusing of light with orbital angular momentum.
AB  - The spatial structure of light with Orbital Angular Momentum, or "twisted light",
      closely resembles the shape of atomic wave functions. It could therefore make
      symmetry-forbidden transitions possible in quantum dots, or "artificial atoms".
      However, the vanishing intensity in the center of an OAM beam usually makes this
      effect weak. Here we show a plasmonic approach to focus OAM light to
      subwavelength dimensions using metallic nanoscale resonant optical antennas. This
      allows to increase the field intensity of OAM light at the typical dimensions of
      quantum dots to an intensity larger than a regular Gaussian beam, which
      corresponds to increasing the interaction strength by 3 orders of magnitude. 

PMID- 25051526
TI  - Beyond Wenzel and Cassie-Baxter: second-order effects on the wetting of rough
      surfaces.
AB  - The Wenzel and Cassie-Baxter models are almost exclusively used to explain the
      contact angle dependence of the structure of rough and patterned solid surfaces.
      However, these two classical models do not always accurately predict the wetting
      properties of surfaces since they fail to capture the effect of many interactions
      occurring during wetting, including, for example, the effect of the disjoining
      pressure and of crystal microstructure, grains, and defects. We call such effects
      the second-order effects and present here a model showing how the disjoining
      pressure isotherm can affect wettability due to the formation of thin liquid
      films. We measure water contact angles on pairs of metallic surfaces with
      nominally the same Wenzel roughness obtained by abrasion and by chemical etching.
      These two methods of surface roughening result in different rough surface
      structure, thus leading to different values of the contact angle, which cannot be
      captured by the Wenzel- and Cassie-type models. The chemical and physical changes
      that occur on the stainless steel and aluminum alloy surfaces as a result of
      intergranular corrosion, along with selective intermetallic dissolution, lead to
      a surface roughness generated on the nano- and microscales. 

PMID- 25051527
TI  - Impact of menstrual cycle phase on endocrine effects of partial sleep restriction
      in healthy women.
AB  - There is extensive evidence that sleep restriction alters endocrine function in
      healthy young men, increasing afternoon cortisol levels and modifying levels of
      other hormones that regulate metabolism. Recent studies have confirmed these
      effects in young women, but have not investigated whether menstrual cycle phase
      influences these responses. The effects on cortisol levels of limiting sleep to
      3h for one night were assessed in two groups of women at different points in
      their menstrual cycles: mid-follicular and mid-luteal. Eighteen healthy, young
      women, not taking oral contraceptives (age: 21.8+/-0.53; BMI: 22.5+/-0.58 [mean+/
      SEM]), were studied. Baseline sleep durations, eating habits and menstrual cycles
      were monitored. Salivary samples were collected at six times of day (08:00,
      08:30, 11:00, 14:00, 17:00, 20:00) during two consecutive days: first after a 10h
      overnight sleep opportunity (Baseline) and then after a night with a 3h sleep
      opportunity (Post-sleep restriction). All were awakened at the same time of day.
      Women in the follicular phase showed a significant decrease (p=0.004) in their
      cortisol awakening responses (CAR) after sleep restriction and a sustained
      elevation in afternoon/evening cortisol levels (p=0.008), as has been reported
      for men. Women in the luteal phase showed neither a depressed CAR, nor an
      increase in afternoon/evening cortisol levels. Secondary analyses examined the
      impact of sleep restriction on self-reported hunger and mood. Menstrual cycle
      phase dramatically altered the cortisol responses of healthy, young women to a
      single night of sleep restriction, implicating effects of spontaneous changes in
      endocrine status on adrenal responses to sleep loss. 

PMID- 25051528
TI  - A non-linear association between self-reported negative emotional response to
      stress and subsequent allostatic load: prospective results from the Whitehall II
      cohort study.
AB  - Previous research suggests that high levels of negative emotions may affect
      health. However, it is likely that the absence of an emotional response following
      stressful events may also be problematic. Accordingly, we investigated whether a
      non-linear association exists between negative emotional response to major life
      events and allostatic load, a multisystem indicator of physiological
      dysregulation. Study sample was 6764 British civil service workers from the
      Whitehall II cohort. Negative emotional response was assessed by self-report at
      baseline. Allostatic load was calculated using cardiovascular, metabolic and
      immune function biomarkers at three clinical follow-up examinations. A non-linear
      association between negative emotional response and allostatic load was observed:
      being at either extreme end of the distribution of negative emotional response
      increased the risk of physiological dysregulation. Allostatic load also increased
      with age, but the association between negative emotional response and allostatic
      load remained stable over time. These results provide evidence for a more nuanced
      understanding of the role of negative emotions in long-term physical health. 

PMID- 25051529
TI  - Guanylate Cyclase-Activating Protein-2 Undergoes Structural Changes upon Binding
      to Detergent Micelles and Bicelles.
AB  - GCAPs are neuronal Ca(2+)-sensors playing a central role in light adaptation.
      GCAPs are N-terminally myristoylated membrane-associated proteins. Although, the
      myristoylation of GCAPs plays an important role in light adaptation its
      structural and physiological roles are not yet clearly understood. The crystal
      structure of GCAP-1 shows the myristoyl moiety inside the hydrophobic core of the
      protein, stabilizing the protein structure; but (2)H-solid-state NMR
      investigations on the deuterated myristoyl moiety of GCAP-2 in the presence of
      liposomes showed that it is inserted into the lipid bilayer. In this study, we
      address the question of the localization of the myristoyl group of Ca(2+)-bound
      GCAP-2, and the influence of CHAPS-, DPC-micelles and DMPC/DHPC-bicelles on the
      structure, and on the localization of the myristoyl group, of GCAP-2 by solution
      state NMR. We also carried out the backbone assignment. Characteristic chemical
      shift differences have been observed between the myristoylated and the non
      myristoylated forms of the protein. Our results support the view that in the
      absence of membrane forming substances the myristoyl moiety is buried inside a
      hydrophobic pocket of GCAP-2 similar to the crystal structure of GCAP-1. Addition
      of CHAPS-micelles and DMPC/DHPC-bicelles cause specific structural changes
      localized in and around the myristoyl binding pocket. We interpret these changes
      as an indication for the extrusion of the myristoyl moiety from its binding
      pocket and its insertion into the hydrophobic interior of the membrane mimic. On
      the basis of the backbone chemical shifts, we propose a structural model of
      myristoylated GCAP-2 in the presence of Ca(2+) and membrane mimetics. 

PMID- 25051530
TI  - Two-step sintering of new potassium sodium niobate ceramics: a high d33 and wide
      sintering temperature range.
AB  - In this work, the two-step sintering technique is used to realize a high
      piezoelectric constant (d33) and wide sintering temperature range (T(S)) in the
      0.955(K(0.42)Na(0.58))(Nb(0.96)Sb(0.04))O3-0.045(Bi(0.5)K(0.5))(0.90)Zn(0.10)ZrO3
      lead-free ceramics. Dense microstructures were developed in the ceramics by two
      step sintering. In the T(S) range of 800-1130  degrees C, the rhombohedral
      tetragonal phase boundary was well maintained, and these ceramics possess
      enhanced dielectric, ferroelectric, and piezoelectric properties. It is of great
      interest to note that a d33 of 323-416 pC/N could be attained in a temperature
      gap range of 330  degrees C. We believe that the two-step sintering could both
      widen the sintering temperature and obtain a high d33 for this material system.

PMID- 25051531
TI  - Tempo-spatially resolved cellular dynamics of human immunodeficiency virus
      transacting activator of transcription (Tat) peptide-modified nanocargos in
      living cells.
AB  - Understanding the cellular uptake mechanism and intracellular fate of
      nanocarriers in living cells is of great importance for the rational design of
      efficient drug delivery cargos as well as the development of robust biomedical
      diagnostic probes. In present study, with a dual wavelength view darkfield
      microscope (DWVD), the tempo-spatially resolved dynamics of Tat peptide
      functionalized gold nanoparticles (TGNPs, with size similar to viruses) in living
      HeLa cells were extensively explored. It was found that energy-dependent
      endocytosis (both clathrin- and caveolae-mediated processes were involved) was
      the prevailing pathway for the cellular uptake of TGNPs. The time-correlated
      dynamic spatial distribution information revealed that TGNPs could not actively
      target the cell nuclei, which is contrary to previous observations based on fixed
      cell results. More importantly, the inheritance of TGNPs to the daughter cells
      through mitosis was found to be the major route to metabolize TGNPs by HeLa
      cells. These understandings on the cellular uptake mechanism and intracellular
      fate of nanocargos in living cells would provide deep insight on how to improve
      and controllably manipulate their translocation efficiency for targeted drug
      delivery. 

PMID- 25051533
TI  - Resource allocation as a driver of senescence: life history tradeoffs produce age
      patterns of mortality.
AB  - We investigate the effects of optimal time and resource allocation on age
      patterns of fertility and mortality for a model organism with (1) fixed maximum
      lifespan, (2) distinct juvenile and adult diets, and (3) reliance on nonrenewable
      resources for reproduction. We ask when it is optimal to tolerate starvation vs.
      conserve resources and then examine the effects of these decisions on adult
      mortality rates. We find that (1) age-related changes in tradeoffs partition the
      life cycle into as many as four discrete phases with different optimal behavior
      and mortality patterns, and (2) given a cost of reproduction, terminal investment
      can produce a signal of actuarial senescence. Also, given limitations imposed by
      non-replenishable resources, individuals beginning adult life with more
      replenishable resources do not necessarily live longer, since they can engage in
      capital breeding and need not defer reproduction to forage; low reproductive
      overheads and low costs of starvation also encourage capital breeding and may
      lead to earlier terminal investment and earlier senescence. We conclude that,
      even for species with qualitatively similar life histories, differences in
      physiological, behavioral and environmental tradeoffs or constraints may strongly
      influence optimal allocation schedules and produce variation in mortality
      patterns and life expectancy. 

PMID- 25051532
TI  - Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation
      in the bone marrow microenvironment.
AB  - Osteoclasts are components of hematopoietic stem cell (HSC) niches, but their
      role as contributors to the HSC homeostasis and release are still controversial.
      We aimed to investigate whether an acute blood loss of 10% of total blood
      content, along with the consequent intense hematopoiesis, would affect osteoclast
      differentiation and activity. Isolated peripheral blood, spleen, and bone marrow
      (BM) cells from bones of hind limbs were investigated for the presence of
      specific subpopulations of osteoclast precursors: B220(-)CD3(-)NK1.1(-)CD11b(
      /low)CD115(+)CD117(+) cells in BM, and B220(-)CD3(-)NK1.1(-)Gr-1(
      )CD11b(+)CD115(+) cells in peripheral blood and spleen as well as the receptor
      activator of nuclear factor kappa-B(+) cycle-arrested quiescent osteoclast
      precursors. Expression of osteoclastogenesis-related genes CD115, receptor
      activator of nuclear factor kappa-B, and cathepsin K, the potential of BM cells
      to form osteoclast-like cells in vitro, and osteoclast activity in vivo were also
      evaluated. We observed an increase in spleen cellularity and myelopoiesis during
      week 1 following blood loss, without any significant effects on BM cellularity or
      BM myeloid precursors, including cells with high osteoclastogenic potential.
      However, at 1 week postbleeding, hematopoiesis significantly promoted the
      expression of cathepsin K, interleukin-34, and bone morphogenetic protein-6.
      Quiescent osteoclast precursors increased significantly in spleen 2 days
      following bleeding, whereas osteoclast activity remained unchanged up to 2 weeks
      postbleeding. Osteoclast-dependent B-cell differentiation was affected at the pre
      B stage of maturation in BM, whereas the Lin(-)Sca-1(+)c-kit(+) population
      expanded in BM and spleen after 2 days postbleeding. Our data demonstrate that an
      acute blood loss promotes differentiation and maturation of osteoclasts at 1 week
      but does not enhance osteoresorption at 2 weeks postbleeding. Our data also
      identify osteoclast differentiation as a consequent and important event in
      establishing HSC homeostasis following hematopoietic stress.

PMID- 25051534
TI  - Assessment of trading partners for China's rare earth exports using a decision
      analytic approach.
AB  - Chinese rare earth export policies currently result in accelerating its
      depletion. Thus adopting an optimal export trade selection strategy is crucial to
      determining and ultimately identifying the ideal trading partners. This paper
      introduces a multi-attribute decision-making methodology which is then used to
      select the optimal trading partner. In the method, an evaluation criteria system
      is established to assess the seven top trading partners based on three
      dimensions: political relationships, economic benefits and industrial security.
      Specifically, a simple additive weighing model derived from an additive utility
      function is utilized to calculate, rank and select alternatives. Results show
      that Japan would be the optimal trading partner for Chinese rare earths. The
      criteria evaluation method of trading partners for China's rare earth exports
      provides the Chinese government with a tool to enhance rare earth industrial
      policies. 

PMID- 25051535
TI  - Sensitive electrochemiluminescence detection for CA15-3 based on immobilizing
      luminol on dendrimer functionalized ZnO nanorods.
AB  - In this study, we constructed a novel electrochemiluminescence (ECL) immunosensor
      for sensitive and selective detection of carbohydrate antigen 15-3 (CA15-3) by
      using polyamidoamine (PAMAM)-functionalized ZnO nanorods (ZNs-PAMAM) as carriers.
      PAMAM dendrimers with hyper-branched and three-dimensional structure were used as
      linked reagents for co-immobilization of luminol and CA15-3 detection antibody on
      the ZNs to prepare the signal probe. In addition, ZNs could hasten the
      decomposition of H2O2 to generate various reactive oxygen species (ROSs) which
      accelerated the ECL reaction of luminol with amplified ECL intensity. Compared
      with luminol in the detection solution, the ECL efficiencies of luminol could be
      improved by immobilizing luminol on the electrode due to the smaller distance
      between luminescence reagent and the electrode surface. Moreover, the
      electrodepositing gold nanoparticles (AuNPs) on the bare glass carbon electrode
      (GCE) with enhanced surface area could capture a large amount of primary anti
      CA15-3 to improve the sensitivity of the immunosensor. Under the optimized
      experimental conditions, a wide linear range of 0.1-120 U mL(-1) was acquired
      with a relatively low detection limit of 0.033 U mL(-1) (S/N=3) for CA15-3.

PMID- 25051536
TI  - Laparoendoscopic single-site surgery using conventional laparoscopic instruments
      and glove port technique in gynecology: a single surgeon's experience.
AB  - STUDY OBJECTIVE: To report a single surgeon's experience with 120
      laparoendoscopic single-site surgery (LESS) procedures using conventional
      laparoscopic instruments and a homemade glove port system to treat benign
      gynecologic diseases. DESIGN: Retrospective chart analysis (Canadian Task Force
      classification III). SETTING: Eulji University Hospital. PATIENTS: One hundred
      twenty patients who underwent LESS performed by a single surgeon to treat benign
      gynecologic diseases between November 2010 and November 2012. INTERVENTION: LESS
      using conventional instrumentation was performed using our specialized glove port
      technique, which consists of the combination of the homemade glove port system
      designed to minimalize collision of the trocar on the tip of the finger of the
      surgical glove, a sufficient rectus fasciotomy, the surgeon's position at the
      patient's head, and adequate positioning of the instruments. MEASUREMENTS AND
      MAIN RESULTS: The LESS procedures performed were laparoscopically assisted
      vaginal hysterectomy (n = 50), ovarian cystectomy (n = 25), myomectomy (n = 14),
      oophorectomy (n = 11), salpingectomy (n = 9), fimbrioplasty or neosalpingstomy (n
      = 7), and adhesiolysis only (n = 4). Median patient age was 40 years, and median
      body mass index was 23. Median operative time was 100 minutes (range, 50-145
      minutes) for laparoscopically assisted vaginal hysterectomy, 70 minutes (range,
      30-150 minutes) for ovarian cystectomy, 107 minutes (range, 65-180 minutes) for
      myomectomy, 55 minutes (range, 25-130 minutes) for oophorectomy, 85 minutes
      (range, 35-110 minutes) for salpingectomy, 70 minutes (range, 25-140 minutes) for
      neosalpingostomy or fimbrioplasty, and 35 minutes (range, 30-60-minutes) for
      adhesiolysis only. All procedures were completed successfully without the need
      for additional ports or conversion to the standard laparoscopic approach. One
      perioperative complication occurred. The complication rate was 83% (1 of 120).
      Other postoperative complications were not observed at follow-up. CONCLUSION: Our
      experience shows that LESS using conventional laparoscopic instruments and our
      glove port technique is a feasible and safe technique for the surgical management
      of various gynecologic conditions. Therefore, our homemade glove port
      laparoscopic system used in our specialized technique provides a simple, cost
      effective approach to LESS and would probably make laparoscopic procedures using
      conventional instruments easier.

PMID- 25051537
TI  - Laparoscopic excision of sacrocolpopexy mesh.
AB  - STUDY OBJECTIVE: To demonstrate surgical maneuvers to facilitate laparoscopic
      excision of sacrocolpopexy mesh and prevent potential complications. DESIGN: Step
      by-step illustration of various surgical techniques using a video compiled from 3
      laparoscopic sacrocolpopexy mesh excision procedures performed at Magee-Womens
      Hospital for various indications (Canadian Task Force classification xx-xx).
      SETTING: Mesh complications such as infection and erosion are frequently managed
      conservatively but often necessitate mesh excision for symptom relief.
      Laparoscopic excision of sacrocolpopexy mesh procedures is typically challenging,
      even in the hands of experienced surgeons. Synthetic mesh, being a foreign body,
      activates an inflammatory process that leads to surrounding tissue fibrosis and
      scar tissue formation that can distort the pelvic anatomy, thereby putting vital
      organs at risk of injury. Such organs include the bladder, rectum, and vagina
      caudally; the left common iliac vein and middle sacral vessels cephalad; and the
      ureters at the level of the vaginal cuff angles. INTERVENTION: Laparoscopic
      excision of sacrocolpopexy mesh. CONCLUSION: When planning laparoscopic
      sacrocolpopexy mesh excision, complications can be prevented with use of proper
      surgical technique. It is important to identify vital structures because they may
      be displaced due to tissue fibrosis. When developing various surgical planes,
      surgeons should first operate in areas that are free of adhesions. This will
      enhance exposure when dissecting the mesh in proximity of scarred tissue and
      vital organs. Use of vaginal and rectal probes helps to delineate the
      vesicovaginal and rectovaginal spaces to prevent bladder and bowel injury.

PMID- 25051538
TI  - Coexisting endosalpingiosis and subserous adenomyosis.

PMID- 25051539
TI  - Neonatal birth waist is positively predicted by second trimester maternal active
      ghrelin, a pro-appetite hormone, and negatively associated with third trimester
      maternal leptin, a pro-satiety hormone.
AB  - INTRODUCTION: In pregnancy physiological mechanisms activated by maternal
      appetite contribute to adequate energy intake for the mother and for the fetus.
      The role of maternal appetite-related peptides and their possible association
      with neonatal energy stores and glucose metabolism have not been investigated as
      yet. The aim was to investigate, during pregnancy, the association of fasting
      maternal appetite-related hormones levels [ghrelin (active), GLP1 (active), total
      PYY and leptin] with neonatal waist, percent total body fat and insulin levels at
      birth. METHODS: Forty-two normal and thirty eight overweight women (mean+/-SD;
      age: 26.9+/-2.5years; pre-pregnancy BMI 26+/-2.2kg/m(2)) were seen during each of
      the three trimesters, had blood sampling and a 75g oral glucose tolerance test.
      At birth, neonates underwent anthropometry and cord blood sampling for c-peptide,
      glucose, insulin. RESULTS: During all three trimesters maternal weight correlated
      positively with percent total neonatal body fat while during the second and third
      trimesters it correlated positively with birth weight. The second trimester
      maternal active ghrelin levels correlated positively with neonatal waist and were
      its best positive predictor. The third trimester maternal active ghrelin levels
      correlated positively with neonatal waist and negatively with percent total
      neonatal body fat, fetal cord blood insulin levels and were the best negative
      predictor of the latter. The third trimester maternal leptin levels correlated
      negatively with neonatal waist. CONCLUSIONS: During pregnancy circulating
      maternal active ghrelin, a pro-appetite hormone, is associated with neonatal
      visceral energy storage (as expressed by neonatal waist). By inhibiting glucose
      driven maternal insulin secretion, ghrelin might ensure adequate fasting glucose
      and nutrient supplies to the fetus while limiting overall fetal adipose tissue
      deposition.

PMID- 25051540
TI  - Chronic lung disease of prematurity and early childhood wheezing: is foetal
      inflammatory response syndrome to blame?
AB  - BACKGROUND: Long-lasting respiratory symptoms have a huge impact on the quality
      of life in prematurely born children. AIMS: We aimed to investigate the perinatal
      and maternal risk factors involved in the development of chronic respiratory
      morbidity in preterm infants, with an emphasis on the importance of Foetal
      Inflammatory Response Syndrome (FIRS). STUDY DESIGN: Prospective cohort study.
      SUBJECTS: Demographic, antenatal, delivery and outcomes data were collected from
      262 infants with less than 32 completed weeks of gestational age, over a 10-year
      period. OUTCOME MEASURES: Presence of chronic lung disease of prematurity and
      early childhood wheezing. RESULTS: In multivariate logistic regression analysis
      the presence of FIRS appears to be the most important risk factor for both,
      chronic lung disease of prematurity (OR 31.05, 95% CI 10.7-87.75, p<0.001) and
      early childhood wheezing (OR 5.63, 95% CI 2.42-13.05, p=0.01). In the alternative
      regression model for early childhood wheezing, with chronic lung disease included
      as a variable, the statistical significance of FIRS completely vanished (OR 1.15,
      95% CI 0.39-3.34, p=0.79), whilst chronic lung disease became the most important
      risk factor (OR 23.45, 95% CI 8.5-63.25, p<0.001). CONCLUSIONS: Prenatal and
      early neonatal events are of utmost importance in the development of chronic
      respiratory symptoms in children. The influence of FIRS on the development of
      chronic respiratory symptoms goes far beyond its impact on gestational age and
      may be related to direct inflammation-mediated lung tissue damage. CLD appears to
      be an intermittent step on the way from FIRS to ECW.

PMID- 25051541
TI  - Can MII-pH values predict the duration of treatment for GERD in preterm infants?
AB  - BACKGROUND: Little is known regarding the prognostic role of Multichannel
      Intraluminal Impedance and pH monitoring (MII/pH) parameters in preterm infants
      with Gastro-Esophageal Reflux Disease (GERD). AIM: Our study aimed to evaluate
      the relationship between MII/pH variables and the duration of pharmacological
      therapy for GERD, in preterm infants with gestational age (GA) <=34weeks.
      SUBJECTS, STUDY DESIGN, OUTCOME MEASURES: We retrospectively reviewed data of all
      newborns with GA <=34weeks that underwent MII/pH in our Neonatal Intensive Care
      Unit (NICU) and pharmacological treatment for GERD. We included them in a 12
      month follow-up program. MII/pH parameters were used as independent variables and
      the duration of pharmacological therapy as dependent variable in linear
      regression models. RESULTS: 16 patients (GA 28.4+/-1.8weeks, BW 1122+/-427g) were
      enrolled into the study. Regression analysis performed on all reflux events
      reported a significant correlation between the duration of pharmacological
      treatment and MII-BEI (r(2)=0.36, p=0.01) and MII-reflux frequency (r(2)=0.33,
      p=0.02). Moreover, regression analysis performed on all events classified
      according to the corresponding pH change - acidic (ac.), weakly acidic (w.ac.) or
      weakly alkaline (w.a.) - showed a significant correlation between the duration of
      pharmacological treatment and MII-w.ac.BEI (r(2)=0.26, p=0.05), MII-w.ac. reflux
      frequency (r(2)=0.44, p=0.01), and MII-proximal w.ac. reflux frequency
      (r(2)=0.35, p=0.02). No statistically significant correlation was found between
      pH-Reflux Index and the duration of treatment. CONCLUSION: The study shows how,
      in our population of preterm infants, MII-parameters could have not only a
      diagnostic role, but also a prognostic value in terms of the duration of
      pharmacological treatment.

PMID- 25051542
TI  - Magic angle Lee-Goldburg frequency offset irradiation improves the efficiency and
      selectivity of SPECIFIC-CP in triple-resonance MAS solid-state NMR.
AB  - The efficiency and selectivity of SPECIFIC-CP, a widely used method for selective
      double cross-polarization in triple-resonance magic angle spinning solid-state
      NMR, is improved by performing the tangential-shaped (13)C irradiation at an
      offset frequency that meets the Lee-Goldburg condition (LG-SPECIFIC-CP). This is
      demonstrated on polycrystalline samples of uniformly (13)C, (15)N labeled N
      acetyl-leucine and N-formyl-Met-Leu-Phe-OH (MLF) at 700MHz and 900MHz (1)H
      resonance frequencies, respectively. For the single (13)Calpha of N-acetyl
      leucine, relative to conventional broad band cross-polarization, the SPECIFIC-CP
      signal has 47% of the intensity. Notably, the LG-SPECIFIC-CP signal has 72% of
      the intensity, essentially the theoretical maximum. There were no other changes
      in the experimental parameters. The three (13)Calpha signals in MLF show some
      variation in intensities, reflecting the relatively narrow bandwidth of a
      frequency-offset procedure, and pointing to future developments for this class of
      experiment. 

PMID- 25051543
TI  - An optimal decisional space for the classification of Alzheimer's disease and
      mild cognitive impairment.
AB  - This paper proposes to combine MRI data with a neuropsychological test, mini
      mental state examination (MMSE), as input to a multi-dimensional space for the
      classification of Alzheimer's disease (AD) and it's prodromal stages-mild
      cognitive impairment (MCI) including amnestic MCI (aMCI) and nonamnestic MCI
      (naMCI). The decisional space is constructed using those features deemed
      statistically significant through an elaborate feature selection and ranking
      mechanism. FreeSurfer was used to calculate 55 volumetric variables, which were
      then adjusted for intracranial volume, age and education. The classification
      results obtained using support vector machines are based on twofold cross
      validation of 50 independent and randomized runs. The study included 59 AD, 67
      aMCI, 56 naMCI, and 127 cognitively normal (CN) subjects. The study shows that
      MMSE scores contain the most discriminative power of AD, aMCI, and naMCI. For AD
      versus CN, the two most discriminative volumetric variables (right hippocampus
      and left inferior lateral ventricle), when combined with MMSE scores, provided an
      average accuracy of 92.4% (sensitivity: 84.0%; specificity: 96.1%). MMSE scores
      are found to improve all classifications with accuracy increments of 8.2% and 12%
      for aMCI versus CN and naMCI versus CN, respectively. Results also show that
      brain atrophy is almost evenly seen on both sides of the brain for AD subjects,
      which is different from right-side dominance for aMCI and left-side dominance for
      naMCI. Furthermore, hippocampal atrophy is seen to be the most significant for
      aMCI, while Accumbens area and ventricle are most significant for naMCI. 

PMID- 25051545
TI  - Caenorhabditis elegans segmentation using texture-based models for motility
      phenotyping.
AB  - With widening interests in using model organisms for reverse genetic approaches
      and biomimmetic microrobotics, motility phenotyping of the nematode
      Caenorhabditis elegans is expanding across a growing array of locomotive
      environments. One ongoing bottleneck lies in providing users with automatic
      nematode segmentations of C. elegans in image sequences featuring complex and
      dynamic visual cues, a first and necessary step prior to extracting motility
      phenotypes. Here, we propose to tackle such automatic segmentation challenges by
      introducing a novel texture factor model (TFM). Our approach revolves around the
      use of combined intensity- and texture-based features integrated within a
      probabilistic framework. This strategy first provides a coarse nematode
      segmentation from which a Markov random field model is used to refine the
      segmentation by inferring pixels belonging to the nematode using an approximate
      inference technique. Finally, informative priors can then be estimated and
      integrated in our framework to provide coherent segmentations across image
      sequences. We validate our TFM method across a wide range of motility
      environments. Not only does TFM assure comparative performances to existing
      segmentation methods on traditional environments featuring static backgrounds, it
      importantly provides state-of-the-art C. elegans segmentations for dynamic
      environments such as the recently introduced wet granular media. We show how such
      segmentations may be used to compute nematode "skeletons" from which motility
      phenotypes can then be extracted. Overall, our TFM method provides users with a
      tangible solution to tackle the growing needs of C. elegans segmentation in
      challenging motility environments. 

PMID- 25051544
TI  - Reduction of edge effect on disk electrodes by optimized current waveform.
AB  - Rectangular pulses applied to disk electrodes result in high current density at
      the edges of the disk, which can lead to electrode corrosion and tissue damage.
      We explored a method for reducing current density and corrosion, by varying the
      leading edge of the current pulse. Finite-element modeling and mathematical
      analysis were used to predict an optimal waveform that reduces current density at
      the edge while also maintaining short pulse duration. An approximation of the
      optimized waveform was implemented experimentally and applied to platinum disk
      electrodes. Surface analysis using energy-dispersive spectroscopy showed
      significant reduction of corrosion on the periphery of these electrodes after
      pulsing, compared to those pulsed with the control rectangular waveform. 

PMID- 25051546
TI  - Energy calibration of the pixels of spectral X-ray detectors.
AB  - The energy information acquired using spectral X-ray detectors allows noninvasive
      identification and characterization of chemical components of a material. To
      achieve this, it is important that the energy response of the detector is
      calibrated. The established techniques for energy calibration are not practical
      for routine use in pre-clinical or clinical research environment. This is due to
      the requirements of using monochromatic radiation sources such as synchrotron,
      radio-isotopes, and prohibitively long time needed to set up the equipment and
      make measurements. To address these limitations, we have developed an automated
      technique for calibrating the energy response of the pixels in a spectral X-ray
      detector that runs with minimal user intervention. This technique uses the X-ray
      tube voltage (kVp) as a reference energy, which is stepped through an energy
      range of interest. This technique locates the energy threshold where a pixel
      transitions from not-counting (off) to counting (on). Similarly, we have
      developed a technique for calibrating the energy response of individual pixels
      using X-ray fluorescence generated by metallic targets directly irradiated with
      polychromatic X-rays, and additionally gamma-rays from (241)Am. This technique
      was used to measure the energy response of individual pixels in CdTe-Medipix3RX
      by characterizing noise performance, threshold dispersion, gain variation and
      spectral resolution. The comparison of these two techniques shows the energy
      difference of 1 keV at 59.5 keV which is less than the spectral resolution of the
      detector (full-width at half-maximum of 8 keV at 59.5 keV). Both techniques can
      be used as quality control tools in a pre-clinical multi-energy CT scanner using
      spectral X-ray detectors. 

PMID- 25051547
TI  - United iterative reconstruction for spectral computed tomography.
AB  - Spectral computed tomography (CT) has attracted considerable attention because of
      its energy-resolving capability in identifying and discriminating materials. The
      use of a narrow energy bin can improve energy resolution. However, a narrow
      energy bin has high noise ratio, which degrades the imaging quality of spectral
      CT. To address this problem, this study exploits the structure correlations of
      images in the energy domain and proposed two types of united iterative
      reconstruction (UIR) algorithms. One type uses the well-reconstructed broad
      spectrum image, with all available photons, as a constraint, whereas the other
      type uses a pseudo narrow-energy image, which is estimated with the use of our
      proposed structure-coupling (SC) method, as a constraint. The SC method utilizes
      local structures to connect images that are reconstructed with broad-spectrum and
      narrow-energy CT datasets. Given a broad-spectrum image, the SC method can
      accurately estimate its corresponding narrow-energy image. Results show that UIR
      algorithms significantly outperform conventional iterative reconstruction
      algorithms for narrow-energy image reconstruction in spectral CT. Among the UIR
      algorithms, SC-UIR yields the best results. 

PMID- 25051548
TI  - Color constancy using 3D scene geometry derived from a single image.
AB  - The aim of color constancy is to remove the effect of the color of the light
      source. As color constancy is inherently an ill-posed problem, most of the
      existing color constancy algorithms are based on specific imaging assumptions
      (e.g., gray-world and white patch assumption). In this paper, 3D geometry models
      are used to determine which color constancy method to use for the different
      geometrical regions (depth/layer) found in images. The aim is to classify images
      into stages (rough 3D geometry models). According to stage models, images are
      divided into stage regions using hard and soft segmentation. After that, the best
      color constancy methods are selected for each geometry depth. To this end, we
      propose a method to combine color constancy algorithms by investigating the
      relation between depth, local image statistics, and color constancy. Image
      statistics are then exploited per depth to select the proper color constancy
      method. Our approach opens the possibility to estimate multiple illuminations by
      distinguishing nearby light source from distant illuminations. Experiments on
      state-of-the-art data sets show that the proposed algorithm outperforms state-of
      the-art single color constancy algorithms with an improvement of almost 50% of
      median angular error. When using a perfect classifier (i.e, all of the test
      images are correctly classified into stages); the performance of the proposed
      method achieves an improvement of 52% of the median angular error compared with
      the best-performing single color constancy algorithm. 

PMID- 25051549
TI  - Video saliency incorporating spatiotemporal cues and uncertainty weighting.
AB  - We propose a novel algorithm to detect visual saliency from video signals by
      combining both spatial and temporal information and statistical uncertainty
      measures. The main novelty of the proposed method is twofold. First, separate
      spatial and temporal saliency maps are generated, where the computation of
      temporal saliency incorporates a recent psychological study of human visual speed
      perception. Second, the spatial and temporal saliency maps are merged into one
      using a spatiotemporally adaptive entropy-based uncertainty weighting approach.
      The spatial uncertainty weighing incorporates the characteristics of proximity
      and continuity of spatial saliency, while the temporal uncertainty weighting
      takes into account the variations of background motion and local contrast.
      Experimental results show that the proposed spatiotemporal uncertainty weighting
      algorithm significantly outperforms state-of-the-art video saliency detection
      models. 

PMID- 25051550
TI  - Fast Hue and Range Preserving Histogram: Specification: Theory and New Algorithms
      for Color Image Enhancement.
AB  - Color image enhancement is a complex and challenging task in digital imaging with
      abundant applications. Preserving the hue of the input image is crucial in a wide
      range of situations. We propose simple image enhancement algorithms which
      conserve the hue and preserve the range (gamut) of the R, G, B channels in an
      optimal way. In our setup, the intensity input image is transformed into a target
      intensity image whose histogram matches a specified, well-behaved histogram. We
      derive a new color assignment methodology where the resulting enhanced image fits
      the target intensity image. We analyse the obtained algorithms in terms of
      chromaticity improvement and compare them with the unique and quite popular
      histogram based hue and range preserving algorithm of Naik and Murthy. Numerical
      tests confirm our theoretical results and show that our algorithms perform much
      better than the Naik-Murthy algorithm. In spite of their simplicity, they compete
      with well-established alternative methods for images where hue-preservation is
      desired.

PMID- 25051551
TI  - Large-margin Learning of Compact Binary Image Encodings.
AB  - The use of high-dimensional features has become a normal practice in many
      computer vision applications. The large dimension of these features is a limiting
      factor upon the number of data points which may be effectively stored and
      processed, however. We address this problem by developing a novel approach to
      learning a compact binary encoding, which exploits both pair-wise proximity and
      class-label information on training data set. Exploiting this extra information
      allows the development of encodings which, although compact, outperform the
      original high-dimensional features in terms of final classification or retrieval
      performance. The method is general, in that it is applicable to both non
      parametric and parametric learning methods. This generality means that the
      embedded features are suitable for a wide variety of computer vision tasks, such
      as image classification and content-based image retrieval. Experimental results
      demonstrate that the new compact descriptor achieves an accuracy comparable to,
      and in some cases better than, the visual descriptor in the original space
      despite being significantly more compact. Moreover, any convex loss function and
      convex regularization penalty (e.g., 'p norm with p 1) can be incorporated into
      the framework, which provides future flexibility.

PMID- 25051552
TI  - Image Sensor Noise Parameter Estimation by Variance Stabilization and Normality
      Assessment.
AB  - High-quality image denoising requires taking into account the dependence of the
      noise distribution on the original image. The parameters of this dependence are
      often unknown and we propose a new method to estimate them here. Using an
      optimization procedure, we find a variance-stabilizing transformation, which
      transforms the input image into an image with signal-independent noise. Principal
      component analysis of blocks of the transformed image allows estimation of the
      variance of the signal-independent noise so that the parameters of the original
      noise model can be computed. The image blocks for processing are selected in such
      a way that they have low stochastic texture strength but preserve the noise
      distribution. The algorithm does not require the original image to have
      homogeneous areas and can accurately process images with regular textures. It has
      high computational efficiency and smaller maximum estimation error compared with
      the state of the art. Our experiments have also shown that denoising with the
      noise parameters estimated by this method leads to the same results as denoising
      with the true noise parameters.

PMID- 25051553
TI  - Joint Segmentation and Recognition of Categorized Objects from Noisy Web Image
      Collection.
AB  - The segmentation of categorized objects addresses the problem of joint
      segmentation of a single category of object across a collection of images, where
      categorized objects are referred to objects in the same category. Most existing
      methods of segmentation of categorized objects made the assumption that all
      images in the given image collection contain the target object. In other words,
      the given image collection is noise free. Therefore, they may not work well when
      there are some noisy images which are not in the same category, such as those
      image collections gathered by a text query from modern image search engines. To
      overcome this limitation, we propose a method for automatic segmentation and
      recognition of categorized objects from noisy Web image collections. This is
      achieved by cotraining an automatic object segmentation algorithm that operates
      directly on a collection of images, and an object category recognition algorithm
      that identifies which images contain the target object. The object segmentation
      algorithm is trained on a subset of images from the given image collection which
      are recognized to contain the target object with high confidence, while training
      the object category recognition model is guided by the intermediate segmentation
      results obtained from the object segmentation algorithm. This way, our co
      training algorithm automatically identifies the set of true positives in the
      noisy Web image collection, and simultaneously extracts the target objects from
      all the identified images. Extensive experiments validated the efficacy of our
      proposed approach on four datasets: 1) the Weizmann horse dataset, 2) the MSRC
      object category dataset, 3) the iCoseg dataset, and 4) a new 30-categories
      dataset including 15,634 Web images with both hand-annotated category labels and
      ground truth segmentation labels. It is shown that our method compares favorably
      with the state-of-the-art, and has the ability to deal with noisy image
      collections.

PMID- 25051554
TI  - A study of multiplicative watermark detection in the contourlet domain using
      alpha-stable distributions.
AB  - In the past decade, several schemes for digital image watermarking have been
      proposed to protect the copyright of an image document or to provide proof of
      ownership in some identifiable fashion. This paper proposes a novel
      multiplicative watermarking scheme in the contourlet domain. The effectiveness of
      a watermark detector depends highly on the modeling of the transform-domain
      coefficients. In view of this, we first investigate the modeling of the
      contourlet coefficients by the alpha-stable distributions. It is shown that the
      univariate alpha-stable distribution fits the empirical data more accurately than
      the formerly used distributions, such as the generalized Gaussian and Laplacian,
      do. We also show that the bivariate alpha-stable distribution can capture the
      across scale dependencies of the contourlet coefficients. Motivated by the
      modeling results, a blind watermark detector in the contourlet domain is designed
      by using the univariate and bivariate alpha-stable distributions. It is shown
      that the detectors based on both of these distributions provide higher detection
      rates than that based on the generalized Gaussian distribution does. However, a
      watermark detector designed based on the alpha-stable distribution with a value
      of its parameter alpha other than 1 or 2 is computationally expensive because of
      the lack of a closed-form expression for the distribution in this case.
      Therefore, a watermark detector is designed based on the bivariate Cauchy member
      of the alpha-stable family for which alpha = 1 . The resulting design yields a
      significantly reduced-complexity detector and provides a performance that is much
      superior to that of the GG detector and very close to that of the detector
      corresponding to the best-fit alpha-stable distribution. The robustness of the
      proposed bivariate Cauchy detector against various kinds of attacks, such as
      noise, filtering, and compression, is studied and shown to be superior to that of
      the generalized Gaussian detector. 

PMID- 25051555
TI  - Online tremor suppression using electromyography and low-level electrical
      stimulation.
AB  - Tremor is one of the most prevalent movement disorders. There is a large
      proportion of patients (around 25%) in whom current treatments do not attain a
      significant tremor reduction. This paper proposes a tremor suppression strategy
      that detects tremor from the electromyographic signals of the muscles from which
      tremor originates and counteracts it by delivering electrical stimulation to the
      antagonist muscles in an out of phase manner. The detection was based on the
      iterative Hilbert transform and stimulation was delivered above the motor
      threshold (motor stimulation) and below the motor threshold (sensory
      stimulation). The system was tested on six patients with predominant wrist
      flexion/extension tremor (four with Parkinson disease and two with Essential
      tremor) and led to an average tremor reduction in the range of 46%-81% and 35%
      48% across five patients when using the motor and sensory stimulation,
      respectively. In one patient, the system did not attenuate tremor. These results
      demonstrate that tremor attenuation might be achieved by delivering electrical
      stimulation below the motor threshold, preventing muscle fatigue and discomfort
      for the patients, which sets the basis for the development of an alternative
      treatment for tremor. 

PMID- 25051556
TI  - Vibrotactile stimulation promotes embodiment of an alien hand in amputees with
      phantom sensations.
AB  - Tactile feedback is essential to intuitive control and to promote the sense of
      self-attribution of a prosthetic limb. Recent findings showed that amputees can
      be tricked to experience this embodiment, when synchronous and modality-matched
      stimuli are delivered to biological afferent structures and to an alien rubber
      hand. Hence, it was suggested to exploit this effect by coupling touch sensors in
      a prosthesis to an array of haptic tactile stimulators in the prosthetic socket.
      However, this approach is not clinically viable due to physical limits of current
      haptic devices. To address this issue we have proposed modality-mismatched
      stimulation and demonstrated that this promotes self-attribution of an alien hand
      on normally limbed subjects. In this work we investigated whether similar effects
      could be induced in transradial amputees with referred phantom sensations in a
      series of experiments fashioned after the Rubber Hand Illusion using vibrotactile
      stimulators. Results from three independent measures of embodiment demonstrated
      that vibrotactile sensory substitution elicits body-ownership of a rubber hand in
      transradial amputees. These results open up promising possibilities in this
      field; indeed miniature, safe and inexpensive vibrators could be fitted into
      commercially available prostheses and sockets to induce the illusion every time
      the prosthesis manipulates an object. 

PMID- 25051557
TI  - Static load bearing exercises of individuals with transfemoral amputation fitted
      with an osseointegrated implant: reliability of kinetic data.
AB  - This study aimed at presenting the intra-tester reliability of the static load
      bearing exercises (LBEs) performed by individuals with transfemoral amputation
      (TFA) fitted with an osseointegrated implant to stimulate the bone remodeling
      process. There is a need for a better understanding of the implementation of
      these exercises particularly the reliability. The intra-tester reliability is
      discussed with a particular emphasis on inter-load prescribed, inter-axis and
      inter-component reliabilities as well as the effect of body weight normalization.
      Eleven unilateral TFAs fitted with an OPRA implant performed five trials in four
      loading conditions. The forces and moments on the three axes of the implant were
      measured directly with an instrumented pylon including a six-channel transducer.
      Reliability of loading variables was assessed using intraclass correlation
      coefficients (ICCs) and percentage standard error of measurement values ( %SEMs
      ). The ICCs of all variables were above 0.9 and the %SEM values ranged between 0
      and 87%. This study showed a high between-participants' variance highlighting the
      lack of loading consistency typical of symptomatic population as well as a high
      reliability between the loading sessions indicating a plausible correct
      repetition of the LBE by the participants. However, these outcomes must be
      understood within the framework of the proposed experimental protocol. 

PMID- 25051559
TI  - A one-class kernel fisher criterion for outlier detection.
AB  - Recently, Dufrenois and Noyer proposed a one class Fisher's linear discriminant
      to isolate normal data from outliers. In this paper, a kernelized version of
      their criterion is presented. Originally on the basis of an iterative
      optimization process, alternating between subspace selection and clustering, I
      show here that their criterion has an upper bound making these two problems
      independent. In particular, the estimation of the label vector is formulated as
      an unconstrained binary linear problem (UBLP) which can be solved using an
      iterative perturbation method. Once the label vector is estimated, an optimal
      projection subspace is obtained by solving a generalized eigenvalue problem. Like
      many other kernel methods, the performance of the proposed approach depends on
      the choice of the kernel. Constructed with a Gaussian kernel, I show that the
      proposed contrast measure is an efficient indicator for selecting an optimal
      kernel width. This property simplifies the model selection problem which is
      typically solved by costly (generalized) cross-validation procedures.
      Initialization, convergence analysis, and computational complexity are also
      discussed. Lastly, the proposed algorithm is compared with recent novelty
      detectors on synthetic and real data sets. 

PMID- 25051558
TI  - Evaluation of the cytotoxic effects of PLGA coated iron oxide nanoparticles as a
      carrier of 5- fluorouracil and mega-voltage X-ray radiation in DU145 prostate
      cancer cell line.
AB  - The purpose of this study was to investigate the uptake and cytotoxic effects of
      magnetic poly lactic-co-glycolic acid (PLGA)-coated iron oxide nanoparticles as a
      carrier of 5-fluorouracil (5-FU) and X-ray on the level of proliferation capacity
      of DU145 prostate carcinoma cell line in monolayer culture. Following monolayer
      culture, DU 145 cells were treated with different concentrations of 5-FU or 5-FU
      loaded nanoparticles for 24 h and 2Gy X-ray (6 Mega-voltage (MV)). The rate of
      nanoparticles penetration was then measured using atomic adsorption spectroscopy
      (AAS). The cytotoxicity effect of these nanoparticles with/ without X-ray
      radiation was evaluated using colony formation assay. Spectroscopy results showed
      that iron content and therefore the cellular uptake of 5-FU loaded nanoparticles
      increased with increasing nanoparticle concentrations. Further, the proliferation
      capacity of the cells decreased with the increase of 5-FU and 5- FU loaded
      nanoparticle concentrations in combination with X-ray radiation. However the
      extent of reduction in colony number following treatment with 5-FU-loaded
      nanoparticles in combination with 2Gy of megavoltage X-ray radiation was
      significantly more than for free 5-FU. Thus, drug-loaded nanoparticles could
      deliver 5-FU more efficiently into the cells. PLGA coated iron oxide
      nanoparticles are therefore effective drug delivery vehicles for 5-FU. PLGA
      coated iron oxide nanoparticles are biocompatible and this coating is an
      appropriate surface that can penetrate into the cells. 

PMID- 25051560
TI  - A new method for data stream mining based on the misclassification error.
AB  - In this paper, a new method for constructing decision trees for stream data is
      proposed. First a new splitting criterion based on the misclassification error is
      derived. A theorem is proven showing that the best attribute computed in
      considered node according to the available data sample is the same, with some
      high probability, as the attribute derived from the whole infinite data stream.
      Next this result is combined with the splitting criterion based on the Gini
      index. It is shown that such combination provides the highest accuracy among all
      studied algorithms. 

PMID- 25051561
TI  - Learning to track multiple targets.
AB  - Monocular multiple-object tracking is a fundamental yet under-addressed computer
      vision problem. In this paper, we propose a novel learning framework for tracking
      multiple objects by detection. First, instead of heuristically defining a
      tracking algorithm, we learn that a discriminative structure prediction model
      from labeled video data captures the interdependence of multiple influence
      factors. Given the joint targets state from the last time step and the
      observation at the current frame, the joint targets state at the current time
      step can then be inferred by maximizing the joint probability score. Second, our
      detection results benefit from tracking cues. The traditional detection
      algorithms need a nonmaximal suppression postprocessing to select a subset from
      the total detection responses as the final output and a large number of selection
      mistakes are induced, especially under a congested circumstance. Our method
      integrates both detection and tracking cues. This integration helps to decrease
      the postprocessing mistake risk and to improve performance in tracking. Finally,
      we formulate the entire model training into a convex optimization problem and
      estimate its parameters using the cutting plane optimization. Experiments show
      that our method performs effectively in a large variety of scenarios, including
      pedestrian tracking in crowd scenes and vehicle tracking in congested traffic. 

PMID- 25051562
TI  - Adaptive neural control of nonlinear MIMO systems with time-varying output
      constraints.
AB  - In this paper, adaptive neural control is investigated for a class of unknown
      multiple-input multiple-output nonlinear systems with time-varying asymmetric
      output constraints. To ensure constraint satisfaction, we employ a system
      transformation technique to transform the original constrained (in the sense of
      the output restrictions) system into an equivalent unconstrained one, whose
      stability is sufficient to solve the output constraint problem. It is shown that
      output tracking is achieved without violation of the output constraint. More
      specifically, we can shape the system performance arbitrarily on transient and
      steady-state stages with the output evolving in predefined time-varying
      boundaries all the time. A single neural network, whose weights are tuned online,
      is used in our design to approximate the unknown functions in the system
      dynamics, while the singularity problem of the control coefficient matrix is
      avoided without assumption on the prior knowledge of control input's bound. All
      the signals in the closed-loop system are proved to be semiglobally uniformly
      ultimately bounded via Lyapunov synthesis. Finally, the merits of the proposed
      controller are verified in the simulation environment. 

PMID- 25051563
TI  - A two-layer recurrent neural network for nonsmooth convex optimization problems.
AB  - In this paper, a two-layer recurrent neural network is proposed to solve the
      nonsmooth convex optimization problem subject to convex inequality and linear
      equality constraints. Compared with existing neural network models, the proposed
      neural network has a low model complexity and avoids penalty parameters. It is
      proved that from any initial point, the state of the proposed neural network
      reaches the equality feasible region in finite time and stays there thereafter.
      Moreover, the state is unique if the initial point lies in the equality feasible
      region. The equilibrium point set of the proposed neural network is proved to be
      equivalent to the Karush-Kuhn-Tucker optimality set of the original optimization
      problem. It is further proved that the equilibrium point of the proposed neural
      network is stable in the sense of Lyapunov. Moreover, from any initial point, the
      state is proved to be convergent to an equilibrium point of the proposed neural
      network. Finally, as applications, the proposed neural network is used to solve
      nonlinear convex programming with linear constraints and L1 -norm minimization
      problems. 

PMID- 25051564
TI  - Generalized single-hidden layer feedforward networks for regression problems.
AB  - In this paper, traditional single-hidden layer feedforward network (SLFN) is
      extended to novel generalized SLFN (GSLFN) by employing polynomial functions of
      inputs as output weights connecting randomly generated hidden units with
      corresponding output nodes. The significant contributions of this paper are as
      follows: 1) a primal GSLFN (P-GSLFN) is implemented using randomly generated
      hidden nodes and polynomial output weights whereby the regression matrix is
      augmented by full or partial input variables and only polynomial coefficients are
      to be estimated; 2) a simplified GSLFN (S-GSLFN) is realized by decomposing the
      polynomial output weights of the P-GSLFN into randomly generated polynomial nodes
      and tunable output weights; 3) both P- and S-GSLFN are able to achieve universal
      approximation if the output weights are tuned by ridge regression estimators; and
      4) by virtue of the developed batch and online sequential ridge ELM (BR-ELM and
      OSR-ELM) learning algorithms, high performance of the proposed GSLFNs in terms of
      generalization and learning speed is guaranteed. Comprehensive simulation studies
      and comparisons with standard SLFNs are carried out on real-world regression
      benchmark data sets. Simulation results demonstrate that the innovative GSLFNs
      using BR-ELM and OSR-ELM are superior to standard SLFNs in terms of accuracy,
      training speed, and structure compactness. 

PMID- 25051565
TI  - Semantic interaction for visual analytics: toward coupling cognition and
      computation.
AB  - Alex Endert's dissertation "Semantic Interaction for Visual Analytics: Inferring
      Analytical Reasoning for Model Steering" described semantic interaction, a user
      interaction methodology for visual analytics (VA). It showed that user
      interaction embodies users' analytic process and can thus be mapped to model
      steering functionality for "human-in-the-loop" system design. The dissertation
      contributed a framework (or pipeline) that describes such a process, a prototype
      VA system to test semantic interaction, and a user evaluation to demonstrate
      semantic interaction's impact on the analytic process. This research is
      influencing current VA research and has implications for future VA research. 

PMID- 25051566
TI  - Incorporating modern OpenGL into computer graphics education.
AB  - University of Stuttgart educators have updated three computer science courses to
      incorporate forward-compatible OpenGL. To help students, they developed an
      educational framework that abstracts some of modern OpenGL's difficult aspects. 

PMID- 25051567
TI  - Weavy: interactive card-weaving design and construction.
AB  - Card weaving is a simple, easy weaving method, but designing patterns is
      typically laborious and requires knowledge, experience, and skill. The Weavy
      system helps users design and weave original patterns with or without repeating
      elements. In the latter case, the system automatically considers constraints such
      as the number of yarn colors and the cards' rotation direction. Following Weavy's
      construction guide, users weave the pattern they've created. Researchers
      exhibited Weavy at the ACM Siggraph 2013 Studio and ran a small workshop for
      children in Japan. In both cases, the participants quickly learned how to use
      Weavy and enjoyed designing and weaving objects. 

PMID- 25051568
TI  - A flexible pinhole camera model for coherent nonuniform sampling.
AB  - The flexible pinhole camera (FPC) allows flexible modulation of the sampling rate
      over the field of view. The FPC is defined by a viewpoint and a map specifying
      the sampling locations on the image plane. The map is constructed from known
      regions of interest with interactive and automatic approaches. The FPC provides
      inexpensive 3D projection that allows rendering complex datasets quickly, in feed
      forward fashion, by projection followed by rasterization. The FPC supports many
      types of data, including image, height field, geometry, and volume data. The
      resulting image is a coherent nonuniform sampling (CoNUS) of the dataset that
      matches the local variation of the dataset's importance. CoNUS images have been
      successfully implemented for remote visualization, focus-plus-context
      visualization, and acceleration of expensive rendering effects such as surface
      geometric detail and specular reflection. A video explaining and demonstrating
      the FPC is at http://youtu.be/kvFe5XjOPNM. 

PMID- 25051569
TI  - The colloidal metamorphosis: time division multiplexing of the reflectance state.
AB  - Specular reflection plays an important role in an image's appearance. However,
      LCDs don't have sufficient contrast to express specular reflection, and ordinary
      projector screens only have diffuse-reflection surfaces. A new display system
      projects ultrasound waves to dynamically change the reflection state of a screen
      made of a colloidal substance--soap film. The system uses time division
      multiplexing of the diffuse and specular states to produce realistic appearances.
      It employs an optical illusion that exploits the characteristics of human sight.
      Optical measurements and a user study validated this approach's effectiveness. 

PMID- 25051570
TI  - Asteroid modeling for testing spacecraft approach and landing.
AB  - Spacecraft exploration of asteroids presents autonomous-navigation challenges
      that can be aided by virtual models to test and develop guidance and hazard
      avoidance systems. Researchers have extended and applied graphics techniques to
      create high-resolution asteroid models to simulate cameras and other spacecraft
      sensors approaching and descending toward asteroids. A scalable model structure
      with evenly spaced vertices simplifies terrain modeling, avoids distortion at the
      poles, and enables triangle-strip definition for efficient rendering. To create
      the base asteroid models, this approach uses two-phase Poisson faulting and
      Perlin noise. It creates realistic asteroid surfaces by adding both crater models
      adapted from lunar terrain simulation and multiresolution boulders. The
      researchers evaluated the virtual asteroids by comparing them with real asteroid
      images, examining the slope distributions, and applying a surface-relative
      feature-tracking algorithm to the models. 

PMID- 25051571
TI  - Putting science first: distinguishing visualizations from pretty pictures.
AB  - How do we tell whether a proposed visualization is a valid pictorial
      representation of the truth or just an accidental but appealing image? Art and
      science can work brilliantly together in visualization science, but we must know
      when, and how, to distinguish them. 

PMID- 25051572
TI  - Computer graphics and cultural heritage, part 2: continuing inspiration for
      future tools.
AB  - The availability of large quantities of cultural-heritage data will enable new,
      previously inconceivable, types of analysis and new applications. Currently, most
      emerging analysis methods are experimental research. It's likely to take many
      years before the research matures and provides cultural-heritage professionals
      with novel research methods that they use routinely. Indeed, we can expect
      further disruptive technologies to emerge in the foreseeable future and a "steady
      state" of continuing rapid change. Part 1 can be found at 10.1109/MCG.2014.47. 

PMID- 25051573
TI  - Adaptive fuzzy output feedback dynamic surface control of interconnected
      nonlinear pure-feedback systems.
AB  - In this paper, an adaptive fuzzy decentralized output feedback control design is
      presented for a class of interconnected nonlinear pure-feedback systems. The
      considered nonlinear systems contain unknown nonlinear uncertainties and the
      states are not necessary to be measured directly. Fuzzy logic systems are
      employed to approximate the unknown nonlinear functions, and then a fuzzy state
      observer is designed and the estimations of the immeasurable state variables are
      obtained. Based on the adaptive backstepping dynamic surface control design
      technique, an adaptive fuzzy decentralized output feedback control scheme is
      developed. It is proved that all the variables of the resulting closed-loop
      system are semi-globally uniformly ultimately bounded, and also that the observer
      and tracking errors are guaranteed to converge to a small neighborhood of the
      origin. Some simulation results and comparisons with the existing results are
      provided to illustrate the effectiveness and merits of the proposed approach. 

PMID- 25051574
TI  - Adaptive dynamic surface control of a class of nonlinear systems with unknown
      direction control gains and input saturation.
AB  - In this paper, adaptive neural network based dynamic surface control (DSC) is
      developed for a class of nonlinear strict-feedback systems with unknown direction
      control gains and input saturation. A Gaussian error function based saturation
      model is employed such that the backstepping technique can be used in the control
      design. The explosion of complexity in traditional backstepping design is avoided
      by utilizing DSC. Based on backstepping combined with DSC, adaptive radial basis
      function neural network control is developed to guarantee that all the signals in
      the closed-loop system are globally bounded, and the tracking error converges to
      a small neighborhood of origin by appropriately choosing design parameters.
      Simulation results demonstrate the effectiveness of the proposed approach and the
      good performance is guaranteed even though both the saturation constraints and
      the wrong control direction are occurred. 

PMID- 25051575
TI  - Prenatal and postnatal serum PCB concentrations and cochlear function in children
      at 45 months of age.
AB  - BACKGROUND: Some experimental and human data suggest that exposure to
      polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of
      previous epidemiologic studies are mixed and generally focus on either prenatal
      or postnatal PCB concentrations exclusively. OBJECTIVES: Our aim was to evaluate
      the association between pre- and postnatal PCB concentrations in relation to
      cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs),
      and to further clarify the critical periods in development where cochlear status
      may be most susceptible to PCBs. METHODS: A total of 351 children from a birth
      cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age.
      Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were
      collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were
      assessed at 11 frequencies in both ears. Multivariate, generalized linear models
      were used to estimate the associations between PCB concentrations at different
      ages and DPOAEs, adjusting for potential confounders. RESULTS: Maternal and cord
      PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher
      postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated
      with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were
      considered as an area-under-the-curve metric, an increase in PCB-153
      concentration from the 25th to the 75th percentile was associated with a 1.6-dB
      SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: -2.6, -0.5; p =
      0.003). CONCLUSIONS: In this study, postnatal rather than maternal or cord PCB
      concentrations were associated with poorer performance on otoacoustic tests at
      age 45 months.

PMID- 25051577
TI  - Evaluation of a communication campaign to improve continuation among first-time
      injectable contraceptive users in Nyando District, Kenya.
AB  - CONTEXT: Communication campaigns might be a viable means of improving
      contraceptive continuation; however, few such interventions aimed at reducing
      contraceptive discontinuation have been evaluated. METHODS: Data were collected
      from independent samples of new injectable users in Nyando District, Kenya-site
      of a communication campaign to increase contraceptive continuation-and in a
      comparison district, nine months before and nine months after intervention
      implementation. Survival analysis was used to compare the intervention and
      comparison groups with respect to the distribution of time until first
      discontinuation of modern method use among women still in need of family
      planning. RESULTS: Exposure to family planning information was high in both the
      treatment and the comparison district before (97% and 85%, respectively) and
      after the intervention (99% and 78%). Postintervention, 5% of women in the
      comparison district discontinued by 98 days, 8% by 196 days and 23% by 294 days;
      the proportions in the treatment district were 4%, 6% and 16%, respectively. No
      significant difference between the districts was found in the ninemonth
      postintervention contraceptive continuation rates. Having method-related side
      effects or health concerns was the reason most consistently associated with
      discontinuation. Other factors associated with discontinuation differed between
      the districts. CONCLUSIONS: Addressing method-related side effects and health
      concerns will be critical in improving continuation of the injectable.

PMID- 25051576
TI  - Effects of developmental activation of the AhR on CD4+ T-cell responses to
      influenza virus infection in adult mice.
AB  - BACKGROUND: Epidemiological and animal studies indicate that maternal exposure to
      pollutants that bind the aryl hydrocarbon receptor (AhR) correlates with poorer
      ability to combat respiratory infection and lower antibody levels in the
      offspring. These observations point to an impact on CD4+ T cells. Yet, the
      consequence of developmental exposure to AhR ligands on the activation and
      differentiation of CD4+ T cells has not been directly examined. OBJECTIVES: Our
      goal was to determine whether maternal exposure to an AhR ligand directly alters
      CD4+ T cell differentiation and function later in life. METHODS: C57BL/6 mice
      were exposed to a prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), in utero and via suckling. We then measured CD4+ T-cell activation and
      differentiation into distinct effector populations in adult offspring that were
      infected with influenza A virus (IAV). Reciprocal adoptive transfers were used to
      define whether modifications in CD4+ T-cell responses resulted from direct
      effects of developmental TCDD exposure on CD4+ T cells. RESULTS: Developmental
      exposure skewed CD4+ T-cell responses to IAV infection. We observed fewer virus
      specific, activated CD4+ T cells and a reduced frequency of conventional CD4+
      effector-cell subsets. However, there was an increase in regulatory CD4+ T cells.
      Direct effects of AhR activation on CD4+ T cells resulted in impaired
      differentiation into conventional effector subsets; this defect was transferred
      to mice that had not been developmentally exposed to TCDD. CONCLUSIONS: Maternal
      exposure to TCDD resulted in durable changes in the responsive capacity and
      differentiation of CD4+ T cells in adult C57BL/6 mice.

PMID- 25051578
TI  - Individual- and community-level influences on the timing of sexual debut among
      youth in Nyanza, Kenya.
AB  - CONTEXT: Delaying sexual debut is an important HIV prevention strategy, yet few
      studies have examined associations between both community- and individual-level
      characteristics and sexual debut among youth in Sub-Saharan Africa. METHODS:
      Cross-sectional survey data collected from 8,183 youth aged 11-17 in 160 schools
      in Nyanza, Kenya, were used to examine the relationships between individual and
      community measures and the timing of sexual debut. Multilevel discrete-time
      hazard models were used to identify bivariate and multivariate associations.
      RESULTS: At the individual level, youth were more likely to have initiated sex
      (or had done so at an earlier age) if they had felt pressure to engage in sex
      from a greater number of sources (odds ratios, 1.3-1.8); perceived that they had
      a small or (among females) moderate chance, rather than no chance, of contracting
      HIV (1.2-1.3); or endorsed a greater number of HIV transmission myths (1.1 for
      both sexes). In addition, males with higher abstinence selfefficacy had a reduced
      risk of sexual debut (0.95). At the community level, males and females had a
      reduced risk of sexual debut if they lived in a community where AIDS deaths were
      publicly acknowledged (0.6-0.8) or the Primary School Action for Better Health
      program had been implemented (0.8-0.95); risk was also reduced among young men
      who lived in communities where HIV was discussed at a greater number of parent
      teacher association meetings (0.9) or where abstinence was the primary AIDS
      prevention message conveyed to youth (0.9). CONCLUSION: Community-level variables
      are frequently associated with sexual debut and should be included in future
      research.

PMID- 25051579
TI  - Knowledge and use of emergency contraception: a multicountry analysis.
AB  - CONTEXT: Globally, evidence on knowledge and use of emergency contraception from
      population-based data is limited, though such information would be helpful in
      increasing access to the method. We examined knowledge and use of emergency
      contraception in 45 countries using population-based survey data. METHODS:
      Demographic and Health Survey (DHS) data on women aged 15-49 were analyzed by
      country in logistic regressions to identify associations between women's
      characteristics and their having heard of emergency contraception or having ever
      used it. Trends were examined, by region and globally, according to individual,
      household and community descriptors, including women's age, education, marital
      status, socioeconomic status, and urban or rural location. RESULTS: The
      proportion of women who had heard of emergency contraception ranged from 2% in
      Chad to 66% in Colombia, and the proportion of sexually experienced women who had
      used it ranged from less than 0.1% in Chad to 12% in Colombia. The odds of having
      heard of or used the method generally increased with wealth, and although the
      relationship between marital status and knowing of the method varied by region,
      never-married women were more likely than married women to have used emergency
      contraception in countries where significant differences existed. In some
      countries, urban residence was associated with having heard of the method, but in
      only three countries were women from urban areas more likely to have used it.
      CONCLUSIONS: Our findings support the need for broader dissemination of
      information on emergency contraception, particularly among low-income
      individuals. Variations in use and knowledge within regions suggest a need for
      programs to be tailored to country-level characteristics.

PMID- 25051580
TI  - Traditional birthspacing practices and uptake of family planning during the
      postpartum period in Ouagadougou: qualitative results.
AB  - CONTEXT: In many low-income countries, postpartum women typically start
      contraception after the resumption of sexual intercourse or menstruation.
      Postpartum breast-feeding and abstinence delay these events. Information is
      needed on women's motivations to rely on these traditional birthspacing practices
      and their difficulties in starting a contraceptive method after a birth in urban
      West Africa. METHODS: In 2012, provider-client interactions and service delivery
      were observed for a week in seven health facilities in Ouagadougou, Burkina Faso,
      and semistructured interviews were conducted with 33 women and 12 men with
      infants younger than 24 months. Existing postpartum family planning services and
      women's transition from traditional practices to a family planning method are
      described. RESULTS: Family planning is scheduled to be delivered at the six-week
      postpartum checkup, which women rarely attend. No women viewed amenorrhea as
      protective against pregnancy, and all had started or planned to start a method
      just before or when they resumed sexual activity. Half of the women abstained for
      six or more months, and some then either adopted a method they used incorrectly
      or did not adopt one at all. The main difficulties included providers'
      requirements for amenorrheic women seeking contraceptives and husbands' refusal
      to refrain from unprotected sex. CONCLUSION: The initial postpartum family
      planning visit should occur right after delivery. Integration of family planning
      into immunization programs would provide opportunities to reach women who did not
      adopt a method early in the postpartum period. Provider barriers for amenorrheic
      women should be ended. Men should be involved in the postpartum family planning
      consultation.

PMID- 25051582
TI  - [Retraction of an article].

PMID- 25051581
TI  - Using mapping of service delivery sites to increase contraceptive availability in
      Kinshasa, Democratic Republic of the Congo.

PMID- 25051583
TI  - Final priority; National Institute on Disability and Rehabilitation Research-
      Rehabilitation Research and Training Centers. Final priority.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a priority under the Advanced Rehabilitation Research Training (ARRT)
      Program administered by the National Institute on Disability and Rehabilitation
      Research (NIDRR). Specifically, we announce a priority for an ARRT on Advanced
      Rehabilitation Research Policy Fellowship. The Assistant Secretary may use this
      priority for competitions in fiscal year (FY) 2014 and later years. We take this
      action to focus research attention on an area of national need. We intend the
      priority to strengthen the capacity of the disability and rehabilitation fields
      to train researchers to conduct advanced policy research in the areas of
      rehabilitation and disability.

PMID- 25051584
TI  - Monolithic erbium- and ytterbium-doped microring lasers on silicon chips.
AB  - We demonstrate monolithic 160-um-diameter rare-earth-doped microring lasers using
      silicon-compatible methods. Pump light injection and laser output coupling are
      achieved via an integrated silicon nitride waveguide. We measure internal quality
      factors of up to 3.8 * 105 at 980 nm and 5.7 * 105 at 1550 nm in undoped
      microrings. In erbium- and ytterbium-doped microrings we observe single-mode 1.5
      um and 1.0-um laser emission with slope efficiencies of 0.3 and 8.4%,
      respectively. Their small footprints, tens of microwatts output powers and sub
      milliwatt thresholds introduce such rare-earth-doped microlasers as scalable
      light sources for silicon-based microphotonic devices and systems.

PMID- 25051585
TI  - Robot visions.
AB  - This article explores the resonating figures of primate, child, and robot in
      contemporary technoscientific corporealizations of the 'almost human'. We take as
      our model (in)organism 'Lucy the Robot Orangutan', roboticist Steve Grand's
      project to create an artificial life form with a mind of its own. One aspect of
      Lucy's figuration by Grand, we argue, which ties her to Haraway's analysis of the
      primate, is of the robot as a model for animal, and more specifically (or
      aspirationally) human, cognition. We follow the trope of 'model organism' as it
      is under discussion within science and technology studies and as an ironic
      descriptor for our own interest in Lucy as an entity/project through which to
      illuminate figurations within robotics more widely. Primate and robot together
      are forms of natureculture that help to clarify how the categories of animal and
      machine are entangled, while making explicit investments in their differences
      from one another, and from the third category of the human. We conclude, again
      following Haraway, by imagining what other possibilities there might be for
      figuring humans, robots, and their relations if we escape the reiterative
      imaginary of the robot as proxy for becoming human.

PMID- 25051586
TI  - Inventing Japan's 'robotics culture': the repeated assembly of science,
      technology, and culture in social robotics.
AB  - Using interviews, participant observation, and published documents, this article
      analyzes the co-construction of robotics and culture in Japan through the
      technical discourse and practices of robotics researchers. Three cases from
      current robotics research--the seal-like robot PARO, the Humanoid Robotics
      Project HRP-2 humanoid, and 'kansei robotics' - show the different ways in which
      scientists invoke culture to provide epistemological grounding and possibilities
      for social acceptance of their work. These examples show how the production and
      consumption of social robotic technologies are associated with traditional crafts
      and values, how roboticists negotiate among social, technical, and cultural
      constraints while designing robots, and how humans and robots are constructed as
      cultural subjects in social robotics discourse. The conceptual focus is on the
      repeated assembly of cultural models of social behavior, organization, cognition,
      and technology through roboticists' narratives about the development of advanced
      robotic technologies. This article provides a picture of robotics as the dynamic
      construction of technology and culture and concludes with a discussion of the
      limits and possibilities of this vision in promoting a culturally situated
      understanding of technology and a multicultural view of science.

PMID- 25051587
TI  - Normalizing Transantiago: on the challenges (and limits) of repairing
      infrastructures.
AB  - This article looks to propose a new way to understand the repair of failing large
      sociotechnical systems. Leaving aside romantic valuations, repair always involves
      a certain degree of normalization. Derived from conceptualizations by Foucault,
      repair as normalization is understood as a particular form of power that, first,
      recognizes a certain normal state to which the failing system should evolve and,
      second, develops different strategies to reach it, usually involving the
      deployment of particular disciplinary devices. The ultimate aim of such practices
      is usually not only the improvement of the system but centrally the maintenance
      of a certain kind of power. In order to show the empirical usability of such
      conceptualization, the article analyzes the case of Transantiago, a thoroughgoing
      reform of the public transport system of Santiago, Chile. The start of
      Transantiago in February 2007 was marred by multiple failures, becoming one of
      the biggest public controversies in the country in recent decades. Given this,
      several different strategies were developed to repair such failures,
      understanding them explicitly as normalization. The article analyzes two
      particular strategies: attempts to change the negative 'public perception' about
      Transantiago through the use of quantitative indicators and the introduction of
      an unexpected type of infrastructure to increase the overall speed of the system.
      Finally, the conclusion analyzes how the conception of repair as normalization
      can help us better understand the complexities involved in dealing with failing
      large sociotechnical systems such as Transantiago, pointing to the need to
      sometimes move beyond repair.

PMID- 25051588
TI  - 'The formula that killed Wall Street': the Gaussian copula and modelling
      practices in investment banking.
AB  - Drawing on documentary sources and 114 interviews with market participants, this
      and a companion article discuss the development and use in finance of the
      Gaussian copula family of models, which are employed to estimate the probability
      distribution of losses on a pool of loans or bonds, and which were centrally
      involved in the credit crisis. This article, which explores how and why the
      Gaussian copula family developed in the way it did, employs the concept of
      'evaluation culture', a set of practices, preferences and beliefs concerning how
      to determine the economic value of financial instruments that is shared by
      members of multiple organizations. We identify an evaluation culture, dominant
      within the derivatives departments of investment banks, which we call the
      'culture of no-arbitrage modelling', and explore its relation to the development
      of Gaussian copula models. The article suggests that two themes from the science
      and technology studies literature on models (modelling as 'impure' bricolage, and
      modelling as articulating with heterogeneous objectives and constraints) help
      elucidate the history of Gaussian copula models in finance.

PMID- 25051589
TI  - 'A device for being able to book P&L': the organizational embedding of the
      Gaussian copula.
AB  - This article, the second of two articles on the Gaussian copula family of models,
      discusses the attitude of 'quants' (modellers) to these models, showing that
      contrary to some accounts, those quants were not 'model dopes' who uncritically
      accepted the outputs of the models. Although sometimes highly critical of
      Gaussian copulas - even 'othering' them as not really being models --they
      nevertheless nearly all kept using them, an outcome we explain with reference to
      the embedding of these models in inter- and intra-organizational processes:
      communication, risk control and especially the setting of bonuses. The article
      also examines the role of Gaussian copula models in the 2007-2008 global crisis
      and in a 2005 episode known as 'the correlation crisis'. We end with the
      speculation that all widely used derivatives models (and indeed the evaluation
      culture in which they are embedded) help generate inter-organizational co
      ordination, and all that is special in this respect about the Gaussian copula is
      that its status as 'other' makes this role evident.

PMID- 25051590
TI  - Making waste management public (or falling back to sleep).
AB  - Human-produced waste is a major environmental concern, with communities
      considering various waste management practices, such as increased recycling,
      landfilling, incineration, and waste-to-energy technologies. This article is
      concerned with how and why publics assemble around waste management issues. In
      particular, we explore Noortje Marres and Bruno Latour's theory that publics do
      not exist prior to issues but rather assemble around objects, and through these
      assemblages, objects become matters of concern that sometimes become political.
      The article addresses this theory of making things public through a study of a
      small city in Ontario, Canada, whose landfill is closed and waste diversion
      options are saturated, and that faces unsustainable costs in shipping its waste
      to the United States, China, and other regions. The city's officials are
      undertaking a cost-benefit assessment to determine the efficacy of siting a new
      landfill or other waste management facility. We are interested in emphasizing the
      complexity of making (or not making) landfills public, by exploring an object in
      action, where members of the public may or may not assemble, waste may or may not
      be made into an issue, and waste is sufficiently routinized that it is not
      typically transformed from an object to an issue. We hope to demonstrate Latour's
      third and fifth senses of politics best account for waste management's trajectory
      as a persistent yet inconsistent matter of public concern.

PMID- 25051591
TI  - Body dirt or liquid gold? How the 'safety' of donated breastmilk is constructed
      for use in neonatal intensive care.
AB  - When mothers of preterm infants are unable to produce sufficient volumes of
      breastmilk, neonatologists in many Western countries prescribe pasteurized donor
      breastmilk. Breastmilk has a paradoxical presence in the neonatal intensive care
      unit while it has therapeutic properties, it also has the potential to transmit
      disease. National health authorities and local neonatal intensive care unit
      policies each delimit the safety of donor milk by focusing on the presence or
      absence of pathogens. It is in this light that breastmilk from the human milk
      bank is both sought and legitimated to minimize safety concerns. This research
      uses data arising from an ethnographic study of two human milk banks and two
      neonatal intensive care units in the United States, and 73 interviews with milk
      donors, neonatal intensive care unit parents and clinicians. The primary research
      question framing the study was 'What are the underlying processes and practices
      that have enabled donor milk to be endorsed as a safe and legitimate feeding
      option in neonatal intensive care units?' This study is framed using three key
      principles of Latour's 'new critique', namely, adding to reality rather than
      debunking it, getting closer to data rather than turning away from fact and
      creating arenas in which to assemble. As a result, conceptions of donor milk's
      safety are expanded. This case study of donor milk demonstrates how Latour's new
      critique can inform science and technology studies approaches to the study of
      safety in health care.

PMID- 25051592
TI  - This is America on drugs.

PMID- 25051593
TI  - [Tribute to Professor Gilles Mentha].

PMID- 25051594
TI  - [Right-sided colonic diverticular disease: quo vadis?].
AB  - Symptomatic diverticular disease of the right colon is a rare entity in our
      latitudes, where it represents only 1.5% of all diverticulitis. In contrary, this
      disease is endemic in Asian countries. Besides, it has several differences with
      its left counterpart. Indeed, a right-sided diverticular disease is more often
      symptomatic, while the risk of complicated episodes seems lower. Right-sided
      diverticular disease usually manifests as right iliac fossa pain or low
      gastrointestinal bleeding. First described on 1912, there are no clear
      guidelines. The approach is usually conservative in Asia; when surgery cannot be
      avoided, a limited resection is performed. In Western countries, a surgical
      approach is more often considered. We reviewed the current literature and propose
      a way to manage right diverticulitis.

PMID- 25051595
TI  - [Gastroesophageal cancer: an update on diagnosis and treatment].
AB  - Esophago-gastric cancer remains a relatively rare pathology with, however, an
      ascending tendency in the recent years due to a variety of predisposing factors.
      An extensive preoperative workup and a thorough multidisciplinary discussion are
      the key elements to define treatment strategy. Surgery is the cornerstone of
      treatment for resectable tumors, even if it is associated with morbidity rates of
      40-60% in medium and high-volume centers. Long-term consequences (e.g.
      malnutrition and late anastomotic stenosis) are present in a high proportion of
      patients and they raise the need for a close follow-up with the collaboration of
      the general practitioner, surgeon and oncologist. This multidisciplinary
      treatment and aftercare has the best chance to offer to the patient not only a
      longer overall survival, but a better quality of life as well.

PMID- 25051596
TI  - [Lung volume reduction (LVR) in severe emphysema: a multidisciplinary approach].
AB  - Most cases of emphysema are managed conservatively. However, in severe
      symptomatic emphysema associated with hyperinflation, lung volume reduction (LVR)
      may be proposed to improve dyspnea, exercice capacity, pulmonary functions, walk
      distance and to decrease long-term mortality. LVR may be achieved either
      surgically (LVRS) or endoscopically (EVLR by valves or coils) according to
      specific clinical criteria. Currently, the optimal approach is discussed in a
      multidisciplinary setting. The latter permits a personalized evaluation the
      patient's clinical status and allows the best possible therapeutic intervention
      to be proposed to the patient.

PMID- 25051597
TI  - [Enhanced Recovery After Surgery--optimal management of the surgical patient].
AB  - Enhanced Recovery After Surgery (ERAS) is a multimodal, standardized and evidence
      based perioperative care pathway. With ERAS, postoperative complications are
      significantly lowered, and, as a secondary effect, length of hospital stay and
      health cost are reduced. The patient recovers better and faster allowing to
      reduce in addition the workload of healthcare providers. Despite the hospital
      discharge occurs sooner, there is no increased charge of the outpatient care.
      ERAS can be safely applied to any patient by a tailored approach. The general
      practitioner plays an essential role in ERAS by assuring the continuity of the
      information and the follow-up of the patient.

PMID- 25051598
TI  - [Cell transplantation: current treatments and future prospects].
AB  - Regenerative medicine aims to replace a body function or specific cell loss. It
      includes therapies at the forefront of modem medicine, issuing from translational
      biomedical research. Transplantation of organs and cells has revolutionized the
      management of patients for whom medical treatment is a failure. Unfortunately,
      organ shortage is limiting treatment possibility. As an example, among the 15,000
      patients with type I diabetes in Switzerland, only approximately 30 can receive a
      pancreas or an islet transplant per year. Second example, 500 patients die each
      year in Switzerland from alcoholic cirrhosis because no treatment is available.
      Transplantation of islet cells, hepatocytes, mesenchymal stem cells or
      dopaminergic neurons represents hope fora therapy available for large populations
      of patients.

PMID- 25051599
TI  - [Robotic-assisted organ transplantation].
AB  - Advanced surgical procedures have traditionally been a domain of open surgery.
      However, minimally invasive approaches are evolving with the development of
      robotic technology which appears capable to overcome technical limitations of
      conventional laparoscopy. While traditionally perceived as impossible indications
      for minimally invasive surgery, reports on robotic organ transplantations have
      surfaced with promising results.

PMID- 25051600
TI  - [Do everything to prevent falls in the second half of human existence].

PMID- 25051601
TI  - ["The function of the welcome". In memory of Jean Oury].

PMID- 25051602
TI  - [Artificial insemination and sexual asepsis].

PMID- 25051603
TI  - [Fever after returning from the World Cup: from what are they suffering?].

PMID- 25051605
TI  - [Electronic patient record: advanced policy].

PMID- 25051604
TI  - [Addictions, alcoholism and baclofen: latest French news].

PMID- 25051606
TI  - [Social security: specific rules for the frontier].

PMID- 25051607
TI  - [Kawasaki disease due to mycotoxin carried by the winds].

PMID- 25051608
TI  - [There's the MOOC in better agreement].

PMID- 25051609
TI  - New and improved methods of analysis for plant food materials.

PMID- 25051610
TI  - Evaluation of a soil incubation method to characterize nitrogen release patterns
      of slow- and controlled-release fertilizers.
AB  - Several technologies have been proposed to characterize the nutrient release
      patterns of slow-release fertilizers (SRF) and controlled-release fertilizers
      (CRF) during the last few decades. These technologies have been developed mainly
      by manufacturers, and are product-specific, based on the regulation and analysis
      of each SRF and CRF product. Despite previous efforts to characterize SRF and CRF
      materials, no standardized, validated method exists to assess their nutrient
      release patterns. However, the increased production and distribution of these
      materials in specialty and nonspecialty markets requires an appropriate method to
      verify product claims and material performance. A soil incubation column leaching
      procedure was evaluated to determine its suitability as a standard method to
      estimate nitrogen (N) release patterns of SRFs and CRFs during 180 days. The
      influence of three soil/sand ratios, three incubation temperatures, and four
      soils on method behavior was assessed using five SRFs and three CRFs. In general,
      the highest soil/sand ratio increased the N release rate of all materials, but
      this effect was more marked for the SRFs. Temperature had the greatest influence
      on N release rates. For CRFs, the initial N release rates and the percentage N
      released/day increased as temperature increased. For SRFs, raising the
      temperature from 25 to 35 degreesC increased initial N release rate and the total
      cumulative N released, and almost doubled the percentage released/day. The
      percentage N released/day from all products generally increased as the texture of
      the soil changed from sandy to loamy (lowa>California>Pennsylvania>Florida). The
      soil incubation technique was demonstrated to be robust and reliable for
      characterizing N release patterns from SRFs and CRFs. The method was
      reproducible, and variations in soil/sand ratio, temperature, and soil had little
      effect on the results.

PMID- 25051611
TI  - Optimization and validation of an accelerated laboratory extraction method to
      estimate nitrogen release patterns of slow- and controlled-release fertilizers.
AB  - Several technologies have been proposed to characterize the nutrient release and
      availability patterns of enhanced-efficiency fertilizers (EEFs), especially slow
      release fertilizers (SRFs) and controlled-release fertilizers (CRFs) during the
      last few decades. These technologies have been developed mainly by manufacturers
      and are product-specific based on the regulation and analysis of each EEF
      product. Despite previous efforts to characterize EEF materials, no validated
      method exists to assess their nutrient release patterns. However, the increased
      use of EEFs in specialty and nonspecialty markets requires an appropriate method
      to verify nutrient claims and material performance. A series of experiments were
      conducted to evaluate the effect of temperature, fertilizer test portion size,
      and extraction time on the performance of a 74 h accelerated laboratory
      extraction method to measure SRF and CRF nutrient release profiles. Temperature
      was the only factor that influenced nutrient release rate, with a highly marked
      effect for phosphorus and to a lesser extent for nitrogen (N) and potassium.
      Based on the results, the optimal extraction temperature set was: Extraction No.
      1-2:00 h at 25 degrees C; Extraction No. 2-2:00 h at 50 degrees C; Extraction No.
      3-20:00 h at 55 degrees C; and Extraction No. 4-50:00 h at 60 degrees C.
      Ruggedness of the method was tested by evaluating the effect of small changes in
      seven selected factors on method behavior using a fractional multifactorial
      design. Overall, the method showed ruggedness for measuring N release rates of
      coated CRFs.

PMID- 25051612
TI  - Statistical correlation of the soil incubation and the accelerated laboratory
      extraction methods to estimate nitrogen release rates of slow- and controlled
      release fertilizers.
AB  - Several technologies have been proposed to characterize the nutrient release
      patterns of enhanced-efficiency fertilizers (EEFs) during the last few decades.
      These technologies have been developed mainly by manufacturers and are product
      specific based on the regulation and analysis of each EEF product. Despite
      previous efforts to characterize nutrient release of slow-release fertilizer
      (SRF) and controlled-release fertilizer (CRF) materials, no official method
      exists to assess their nutrient release patterns. However, the increased
      production and distribution of EEFs in specialty and nonspecialty markets
      requires an appropriate method to verify nutrient claims and material
      performance. Nonlinear regression was used to establish a correlation between the
      data generated from a 180-day soil incubation-column leaching procedure and 74 h
      accelerated lab extraction method, and to develop a model that can predict the
      180-day nitrogen (N) release curve for a specific SRF and CRF product based on
      the data from the accelerated laboratory extraction method. Based on the R2 >
      0.90 obtained for most materials, results indicated that the data generated from
      the 74 h accelerated lab extraction method could be used to predict N release
      from the selected materials during 180 days, including those fertilizers that
      require biological activity for N release.

PMID- 25051613
TI  - Determination of phosphorus and potassium in commercial inorganic fertilizers by
      inductively coupled plasma-optical emission spectrometry: single-laboratory
      validation.
AB  - A two-part single-laboratory validation study was conducted for determination of
      the P and K content in commercial fertilizer materials by inductively coupled
      plasma-optical emission spectrometry (ICP-OES). While several methods exist for
      determination of P and K in fertilizer products, the main focus of this study was
      on ICP-OES determination, which offers several unique advantages. Fertilizer
      samples with consensus P and K values from the Magruder and Association of
      Fertilizer and Phosphate Chemists (AFPC) check sample programs were selected for
      this study. Validation materials ranging from 4.4 to 52.4% P205 (1.7 to 22.7% P)
      and 3 to 62% K20 (2.5 to 51.5% K) were utilized. Because all P and K compounds
      contained in fertilizer materials are not "available" for plants to use, this
      study was conducted in two parts. Part A focused on ammonium citrate-disodium
      EDTA as the extraction solvent, as it estimates the pool of fertilizer P and K
      that is considered available to plants. Part B focused on hydrochloric acid as
      the digestion solvent, as it estimates the total P and K content of the
      fertilizer product. Selectivity studies indicated that this method can have a
      high bias for fertilizer products containing sources of phosphite or organic P
      compared to gravimetric or colorimetric methods that measure just orthophosphate.
      Provided the analytical challenges outlined in this study are addressed, this
      method offers the potential for a quick, accurate, and safe alternative for
      determining the P and K content of commercial inorganic fertilizer materials.

PMID- 25051615
TI  - Validation for the determination of biuret in water-soluble, urea-based
      commercial inorganic fertilizer materials, urea solutions, and sulfur-coated urea
      products by reversed-phase liquid chromatography: single-laboratory validation of
      an extension of AOAC official methods 2003.14.
AB  - A single-laboratory validation (SLV) study for the LC determination of biuret in
      dry and liquid urea-based commercial fertilizers was conducted. A total of 23
      samples were used: 11 commercial dry urea products, two urea ammonium nitrate
      products, eight liquid urea-based commercial fertilizers, and four sulfur-coated
      urea samples from different sources. In addition, one biuret standard from
      Aldrich and one sample from the Magruder check sample program were used as
      validation samples. The proposed method is an extension of AOAC Official Method
      2003.14 and is based on dissolution of the test portion in the LC mobile phase
      and determination by HPLC. The system is linear over a concentration range of
      1.00-4.50 mg/L biuret, with a correlation coefficient > or = 0.9999. The biuret
      was well- separated from urea in the commercial urea samples, and from other
      constituents in the commercial liquid fertilizer with no observed interferences.
      Recoveries were determined by spiking four of the validation materials with a
      known amount of biuret standard and measuring the biuret level according to the
      method. The averaged recovery was 97%. Method precision was determined by
      quadruplicate analyses of four of the liquid and six of the commercially
      available dry urea validation materials using three and four replicate analyses.
      For the liquid fertilizer analyses, the RSD ranged from 7.04 to 13.31%. For the
      dry urea analyses, the RSDs ranged from 5.68 to 14.34%. Instrument precision was
      evaluated at the test initiation by using seven injections of five biuret
      standard solutions. SD varied from 0.27 to 1.02%, with RSDs averaging 1.14%. The
      LOD was determined to be 0.009% biuret in material, while the LOQ was determined
      to be 0.031% biuret in material. In addition to the intralaboratory study,
      interlaboratory studies were performed by two other outside laboratories using
      this method. Over a concentration range of 0.2 to 0.9% biuret, the average SD was
      0.11%, the average RSD was 21.16%, and the average HorRat value was 4.73%.
      Furthermore, comparative studies for biuret using AOAC Official Methods 960.04
      and 976.01 with the proposed LC method were performed. The three methods produced
      very close results; however, the two AOAC methods generate hazardous wastes and
      are more tedious. On the basis of accuracy and precision of the results for this
      SLV study, it is recommended that this method be collaboratively studied for the
      determination of biuret in dry and liquid urea-based commercial fertilizer
      materials.

PMID- 25051614
TI  - Simultaneous determination of arsenic, cadmium, calcium, chromium, cobalt,
      copper, iron, lead, magnesium, manganese, molybdenum, nickel, selenium, and zinc
      in fertilizers by microwave acid digestion and inductively coupled plasma-optical
      emission spectrometry detection: single-laboratory validation of a modification
      and extension of AOAC 2006.03.
AB  - A single-laboratory validation study was conducted for the simultaneous
      determination of arsenic, cadmium, calcium, cobalt, copper, chromium, iron, lead,
      magnesium, manganese, molybdenum, nickel, selenium, and zinc in all major types
      of commercial fertilizer products by microwave digestion and inductively coupled
      plasma-optical emission spectroscopy analysis. This validation study proposes an
      extension and modification of AOAC 2006.03. The extension is the inclusion of
      calcium, copper, iron, magnesium, manganese, and zinc, and the modification is
      incorporation of hydrochloric acid in the digestion system. This dual acid
      digestion utilizes both hydrochloric and nitric acids in a 3 to 9 mL volume
      ratio/100 mL. In addition to 15 of the 30 original validation materials used in
      the 2006.03 collaborative study, National Institute of Standards and Technology
      Standard Reference Material 695 and Magruder 2009-06 were incorporated as
      accuracy materials. The main benefits of this proposed method are a significant
      increase in laboratory efficiency when compared to the use of both AOAC Methods
      965.09 and 2006.03 to achieve the same objective and an enhanced recovery of
      several metals.

PMID- 25051616
TI  - A new standardized method for quantification of humic and fulvic acids in humic
      ores and commercial products.
AB  - Increased use of humic substances in agriculture has generated intense interest
      among producers, consumers, and regulators for an accurate and reliable method to
      quantify humic acid (HA) and fulvic acid (FA) in raw ores and products. Here we
      present a thoroughly validated method, the new standardized method for
      determination of HA and FA contents in raw humate ores and in solid and liquid
      products produced from them. The methods used for preparation of HA and FA were
      adapted according to the guidelines of the International Humic Substances Society
      involving alkaline extraction followed by acidification to separate HA from the
      fulvic fraction. This is followed by separation of FA from the fulvic fraction by
      adsorption on a nonionic macroporous acrylic ester resin at acid pH. It differs
      from previous methods in that it determines HA and FA concentrations
      gravimetrically on an ash-free basis. Critical steps in the method, e.g., initial
      test portion mass, test portion to extract volume ratio, extraction time, and
      acidification of alkaline extract, were optimized for maximum and consistent
      recovery of HA and FA. The method detection limits for HA and FA were 4.62 and
      4.8 mg/L, respectively. The method quantitation limits for HA and FA were 14.7
      and 15.3 mg/L, respectively.

PMID- 25051617
TI  - Determination of total sulfur in fertilizers by high temperature combustion:
      single-laboratory validation.
AB  - Asingle-laboratory validation study was conducted for the determination of total
      sulfur (S) in a variety of common, inorganic fertilizers by combustion. The
      procedure involves conversion of S species into SO2 through combustion at 1150
      degrees C, absorption then desorption from a purge and trap column, followed by
      measurement by a thermal conductivity detector. Eleven different validation
      materials were selected for study, which included four commercial fertilizer
      products, five fertilizers from the Magruder Check Sample Program, one reagent
      grade product, and one certified organic reference material. S content ranged
      between 1.47 and 91% as sulfate, thiosulfate, and elemental and organically bound
      S. Determinations of check samples were performed on 3 different days with four
      replicates/day. Determinations for non-Magruder samples were performed on 2
      different days. Recoveries ranged from 94.3 to 125.9%. ABS SL absolute SD among
      runs ranged from 0.038 to 0.487%. Based on the accuracy and precision
      demonstrated here, it is recommended that this method be collaboratively studied
      for the determination of total S in fertilizers.

PMID- 25051618
TI  - Determination of total arsenic and arsenic(III) in phosphate fertilizers by
      hydride generation atomic absorption spectrometry after ultrasound-assisted
      extraction based on a control acid media.
AB  - An ultrasound-assisted extraction procedure was developed for determination of
      inorganic arsenic (As) in phosphate fertilizer by hydride generation atomic
      absorption spectrometry. The variables that affect the hydride generation step
      were optimized, including the reducer, acid, sample flow rate, and concentrations
      of the acid and reducer. The determination of As(lll) was performed through the
      simple control of solution pH with a 0.5 M citric acid-sodium citrate buffer
      solution at pH 4.5, and total As was determined after a pre-reduction reaction
      with 1.0% (w/v) thiourea. Ultrasound-assisted acid extraction was performed, and
      the parameters sonication time and acid and Triton X-114 concentrations were
      optimized using a 23 factorial design and central composite design. LODs for
      As(lll) and total As were 0.029 and 0.022 microg/L, respectively. The accuracy of
      the method was confirmed with certified reference materials. The method was
      successfully applied in the determination of inorganic As in phosphate fertilizer
      samples.

PMID- 25051619
TI  - Evaluation of commonly used methods for the analysis of acid-soluble phosphate in
      internationally traded inorganic fertilizers.
AB  - Several methodologies are used throughout the world to determine phosphate
      concentration (measured as PO4 and expressed as % P2O5) in fertilizers.
      Concentrated phosphate materials, including diammonium phosphate (DAP) and
      monoammonium phosphate (MAP), are traded in large volumes (millions of metric
      tons) internationally. The International Fertilizer Association (IFA) identified
      a need to assess the methods currently being used to measure the phosphate
      content for suitability (scope), accuracy, and repeatability. Even small
      discrepancies in the expressed P2O5 content can have a major financial impact on
      buyers and sellers as contracts are settled and import regulations are imposed.
      The IFA's Technical Committee selected a working group to address issues dealing
      with harmonization of fertilizer sampling and analytical methodologies. The
      working group identified phosphate content in DAP and MAP fertilizers as a major
      concern for commerce. The working group initiated a method screening and
      comparison project to assess method performance and to determine which methods,
      if any, could be considered best practice methods and, therefore, be deemed
      acceptable for use by the industry. In order to systematically review the
      acceptability of methods for consideration, the task force developed an
      assessment protocol outlined in a white paper involving three steps: (1) compile
      all known relevant methods practiced in global fertilizer trade, (2) review and
      evaluate methods based upon specific evaluation criteria, and (3) compare the
      methods that most closely fit the evaluation criteria by multilaboratory analysis
      of unknown materials for accuracy and repeatability. Six methods were evaluated
      for analysis of total phosphate in concentrated phosphate products. From these
      methods, four were determined to be acceptable as best practice methods. The
      study members proposed three of the methods, while a fourth method was commonly
      used among the participating laboratories. This publication is a summary of the
      method comparison process and statistical evaluation of analysis of total
      phosphate content in concentrated phosphate fertilizers.

PMID- 25051620
TI  - Testing of commonly used mixing and sampling procedures to evaluate fertilizer
      blends prepared with matched and mismatched particle sizes.
AB  - Bulk blending of dry fertilizers is a common practice in the United States and
      around the world. This practice involves the mixing (either physically or
      volumetrically) of concentrated, high analysis raw materials. Blending is
      followed by bagging (for small volume application such as lawn and garden
      products), loading into truck transports, and spreading. The great majority of
      bulk blended products are not bagged but handled in bulk and transferred from the
      blender to a holding hopper. The product is then transferred to a transport
      vehicle, which may, or may not, also be a spreader. If the primary transport
      vehicle is not a spreader, then there is another transfer at the user site to a
      spreader for application. Segregation of materials that are mismatched due to
      size, density, or shape is an issue when attempting to effectively sample or
      evenly spread bulk blended products. This study, prepared in coordination with
      and supported by the Florida Department of Agriculture and Consumer Services and
      the Florida Fertilizer and Agrochemical Association, looks at the impact of
      varying particle size as it relates to blending, sampling, and application of
      bulk blends. The study addresses blends containing high ratios of N-P-K materials
      and varying (often small) quantities of the micronutrient Zn.

PMID- 25051621
TI  - Process improvement for regulatory analyses of custom-blend fertilizers.
AB  - Chemical testing of custom-blend fertilizers is essential to ensure that the
      products meet the formulation requirements. For purposes of proper crop nutrition
      and consumer protection, regulatory oversight promotes compliance and particular
      attention to blending and formulation specifications. Analyses of custom-blend
      fertilizer products must be performed and reported within a very narrow window in
      order to be effective. The Colorado Department of Agriculture's Biochemistry
      Laboratory is an ISO 17025 accredited facility and conducts analyses of custom
      blend fertilizer products primarily during the spring planting season. Using the
      Lean Six Sigma (LSS) process, the Biochemistry Laboratory has reduced turnaround
      times from as much as 45 days to as little as 3 days. The LSS methodology focuses
      on waste reduction through identifying: non-value-added steps, unneeded process
      reviews, optimization of screening and confirmatory analyses, equipment
      utilization, nonessential reporting requirements, and inefficient personnel
      deployment. Eliminating these non-value-added activities helped the laboratory
      significantly shorten turnaround time and reduce costs. Key improvement elements
      discovered during the LSS process included: focused sample tracking, equipment
      redundancy, strategic supply stocking, batch size optimization, critical sample
      paths, elimination of nonessential QC reviews, and more efficient personnel
      deployment.

PMID- 25051622
TI  - Determination of kjeldahl nitrogen in fertilizers by AOAC official methods
      978.02: effect of copper sulfate as a catalyst.
AB  - In AOAC Official Method 955.04, Nitrogen (Total) in Fertilizers, Kjeldahl Method,
      fertilizer materials are analyzed using mercuric oxide or metallic mercury HgO or
      Hg) as a catalyst. AOAC Official Methods 970.02, Nitrogen (Total) in Fertilizers
      is a comprehensive total nitrogen (including nitrate nitrogen) method adding
      chromium metal. AOAC Official Method 978.02, Nitrogen (Total) in Fertilizers is a
      modified comprehensive nitrogen method used to measure total nitrogen in
      fertilizers with two types of catalysts. In this method, either copper sulfate or
      chromium metal is added to analyze for total Kjeldahl nitrogen. In this study,
      the part of AOAC Official Method 978.02 that is for nitrate-free fertilizer
      products was modified. The objective was to examine the necessity of copper
      sulfate as a catalyst for the nitrate-free fertilizer products. Copper salts are
      not environmentally friendly and are considered pollutants. Products such as
      ammonium sulfate, diammonium phosphate, monoammonium phosphate, urea-containing
      fertilizers such as isobutylene diurea (IBDU), and urea-triazone fertilizer
      solutions were examined. The first part of the study was to measure Kjeldahl
      nitrogen as recommended by AOAC Official Method 978.02. The second part of the
      study was to exclude the addition of copper sulfate from AOAC Official Method
      978.02 to examine the necessity of copper sulfate as a catalyst in nitrate-free
      fertilizers, which was the primary objective. Our findings indicate that copper
      sulfate can be eliminated from the method with no significant difference in the
      results for the nitrogen content of the fertilizer products.

PMID- 25051623
TI  - Developing a competency framework for U.S. state food and feed testing laboratory
      personnel.
AB  - A competency-based training curriculum framework for U.S. state food and feed
      testing laboratories personnel is being developed by the International Food
      Protection Training Institute (IFPTI) and three partners. The framework will help
      laboratories catalog existing training courses/modules, identify training gaps,
      inform training curricula, and create career-spanning professional development
      learning paths, ensuring consistent performance expectations and increasing
      confidence in shared test results. Ultimately, the framework will aid
      laboratories in meeting the requirements of ISO/IEC 17025 (2005) international
      accreditation and the U.S. Food Safety Modernization Act (U.S. Public Law 111
      353). In collaboration with the Association of Food and Drug Officials, the
      Association of Public Health Laboratories, and the Association of American Feed
      Control Officials, IFPTI is carrying out the project in two phases. In 2013, an
      expert panel of seven subject matter experts developed competency and curriculum
      frameworks for five professional levels (entry, mid-level, expert,
      supervisor/manager, and senior administration) across four competency domains
      (technical, communication, programmatic, and leadership) including approximately
      80 competencies. In 2014 the expert panel will elicit feedback from peers and
      finalize the framework.

PMID- 25051624
TI  - HPTLC method for simultaneous determination of piperine, embeline, and carvone in
      the ayurvedic formulation Catpusphadhya churna.
AB  - Churnas are an important group of formulations used by traditional physicians to
      treat various types of diseases. The principle of using a churna is based on the
      fact that the therapeutic value of most substances greatly increases when they
      are reduced to a very fine state of subdivision. Catpusphadhya churna, as per the
      Ayurvedic system of Indian medicine, is used for acute rheumatoid arthritis. In
      the present study, an attempt was made to develop an HPTLC method for the
      quantitative determination of piperine, embeline, and carvone in a laboratory
      prepared formulation. Raw materials used in formulations were obtained from two
      different suppliers and were subjected to methanol extractions by using a Soxhlet
      apparatus. Piperine, embeline, and carvone were quantified in the extracts by
      using HPTLC. The detection and quantification were performed at 254 nm. The
      formulation contained 2.35% (w/w) of piperine, 4.86% (w/w) of embeline, and 1.48%
      (v/w) of carvone. Linearity studies indicated that piperine, embeline, and
      carvone were in the linear ranges, while the recovery studies revealed a recovery
      of 99.32% (w/w) of piperine, 101.82% (w/w) of embeline, and 100.09% (v/w) of
      carvone, thus proving the accuracy of the analysis. The developed HPTLC method
      resolved and quantified piperine, embeline, and carvone effectively, so it could
      be an important method for the QC of polyherbal formulations.

PMID- 25051625
TI  - Simultaneous determination of eight flavonoids in the flowers of Matricaria
      chamomilla by high performance liquid chromatography.
AB  - An HPLC method was developed for simultaneous determination of five flavones
      (apigenin, three apigenin 7-O-glucoside acylated derivatives, and luteolin) and
      three methoxylated flavonols in Matricaria chamomilla. Full validation of the
      assay was carried out including linearity, LODs, LOQs, precision, repeatability,
      stability, and accuracy. The results demonstrated that the method developed was
      simple, accurate, and reliable. Five batches of M. chamomilla samples were
      determined using the developed method, and total contents of the eight flavonoids
      ranged from 1.843 to 2.134 mg/g. Among them, the content of apigenin was the
      highest with values of 0.538 to 0.618 mg/g. In addition, the extract solution
      from M. chamomilla exhibited a significant dose-dependent inhibition of 2,2
      diphenyl-1-picrylhydrazyl (DPPH) activity, with a 50% inhibition (SC50) at a
      concentration of 3.06 +/- 0.09 mg/mL, and the flavonoids apigenin-7-O-(6"-acetyl)
      glucoside, luteolin, apigenin, eupatolitin, and chrysosplenol D played an
      important role in the antioxidant activities of the extract solution from M.
      chamomilla.

PMID- 25051626
TI  - Analysis of water-soluble polysaccharides in an edible medicinal plant Epimedium:
      method development, validation, and application.
AB  - Water-soluble polysaccharides are important constituents with evident health
      benefits in Epimedium. The aim of this study was to establish a specific,
      accurate, reproducible, and sensitive phenol-sulfuric acid method for the
      quantitative assay of Epimedium polysaccharides and to determine polysaccharides
      in Epimedium samples from Chinese markets. Galactose was adopted as the standard
      monosaccharide, and 486 nm was chosen as the detection wavelength. The optimal
      conditions for the color reaction were obtained using single factor experiments
      and an orthogonal test: temperature, 20 degrees C; amount of 5% phenol, 0.3 mL;
      amount of concentrated sulfuric acid, 3.5 mL; incubation time, 20 min; and
      addition sequence, phenol-sample-sulfuric acid. The colored sample solution after
      chromogenic reaction exhibited high stability within 2 h. The calibration curve
      was linear within the range 5.00-60.00 micro g/mL, and the correlation
      coefficient of the regression equation was 0.999. LOD and LOQ were 1.65 and 5.00
      microg/mL, respectively. Recovery, intraday precision, interday precision, and
      accuracy were 97.43 to 103.80%, 0.73 to 3.48%, 1.21 to 2.75%, and 97.74 to
      101.62%, respectively. Polysaccharides in 26 samples of Epimedium collected from
      different provinces of China were quantified by the proposed colorimetric method,
      and a large variation of contents of polysaccharides was observed among these
      samples.

PMID- 25051627
TI  - Simultaneous determination of atorvastatin calcium and olmesartan medoxomil in a
      pharmaceutical formulation by reversed phase high-performance liquid
      chromatography, high-performance thin-layer chromatography, and UV
      spectrophotometric methods.
AB  - Validated RP-HPLC, HPTLC, and UV spectrophotometric methods have been developed
      for the simultaneous determination of atorvastatin calcium (ATV) and olmesartan
      medoxomil (OLM) in a pharmaceutical formulation. The RP-HPLC separation was
      achieved on a Kromasil C18 column (250 x 4.6 mm, 5 microm particle size) using
      0.01 M potassium dihydrogen o-phosphate (pH 4 adjusted with o-phosphoric acid)
      acetonitrile (50 + 50, v/v) as the mobile phase at a flow rate of 1.5 mL/min.
      Quantification was achieved by UV detection at 276 nm. The HPTLC separation was
      achieved on precoated silica gel 60F254 plates using chloroform-methanol
      acetonitrile (4 + 2+ 4, v/v/v) mobile phase. Quantification was achieved with UV
      detection at 276 nm. The UV-Vis spectrophotometric method was based on the
      simultaneous equation method that involves measurement of absorbance at two
      wavelengths, i.e., 255 nm (lambda max of OLM) and 246.2 nm (lambda max of ATV) in
      methanol. All three methods were validated as per International Conference on
      Harmonization guidelines. The proposed methods were simple, precise, accurate,
      and applicable for the simultaneous determination of ATV and OLM in a marketed
      formulation. The results obtained by applying the proposed methods were
      statistically analyzed and were found satisfactory.

PMID- 25051628
TI  - SAS molecular tests Escherichia coli O157 detection kit. Performance tested
      method 031203.
AB  - The SAS Molecular tests Escherichia coli O157 Detection method, a loop-mediated
      isothermal amplification method, performed as well as or better than the U.S.
      Department of Agriculture, Food Safety Inspection Service Microbiology Laboratory
      Guidebook and the U.S. Food and Drug Administration Bacteriological Analytical
      Manual reference methods for ground beef, beef trim, bagged mixed lettuce, and
      fresh spinach. Ground beef (30% fat, 25 g test portion) was validated for 7-8 h
      enrichment, leafy greens were validated in a 6-7 h enrichment, and ground beef
      (30% fat, 375 g composite test portion) and beef trim (375 g composite test
      portion) were validated in a 16-20 h enrichment. The method performance for meat
      and leafy green matrixes was also shown to be acceptable under conditions of co
      enrichment with Salmonella. Thus, after a short co-enrichment step, ground beef,
      beef trim, lettuce, and spinach can be tested for both Salmonella and E. coli
      O157. The SAS Molecular tests Salmonella Detection Kit was validated using the
      same test portions as for the SAS Molecular tests E. coli O157 Detection Kit and
      those results are presented in a separate report. Inclusivity and exclusivity
      testing revealed no false negatives and no false positives among the 50 E. coli
      0157 strains, including H7 and non-motile strains, and 30 non-E. coli O157
      strains examined. Finally, the method was shown to be robust when variations to
      DNA extract hold time and DNA volume were varied. The method comparison and
      robustness data suggest a full 7 h enrichment time should be used for 25 g ground
      beef test portions.

PMID- 25051629
TI  - SAS molecular tests Salmonella detection kit. Performance tested method 021202.
AB  - The SAS Molecular tests Salmonella Detection method, a Loop-mediated Isothermal
      Amplification method, performed as well as or better than the U.S. Department of
      Agriculture-Food Safety Inspection Service Microbiology Laboratory Guidebook and
      the U.S. Food and Drug Administration Bacteriological Analytical Manual reference
      methods for ground beef, beef trim, ground turkey, chicken carcass rinses, bagged
      mixed lettuce, and fresh spinach. The ground beef (30% fat, 25 g test portion),
      poultry matrixes and leafy greens were validated in a 6-7 h enrichment, and
      ground beef (30% fat, 375 g composite test portion) and beef trim (375 g
      composite test portion) were validated in a 16-20 h enrichment. The method
      performance for meat and leafy green matrixes was shown to be acceptable under
      conditions of co-enrichment with Escherichia coli 0157. Thus, after a short 6-7 h
      co-enrichment step, ground beef, beef trim, lettuce, and spinach can be tested
      for both Salmonella and E. coli O157. Inclusivity and exclusivity testing
      revealed no false negatives and no false positives among the 100 Salmonella
      serovars and 30 non-Salmonella species examined. The method was shown to be
      robust when enrichment time, DNA extract hold time, and DNA volume were varied.

PMID- 25051630
TI  - Veriflow Campylobacter. Performance tested method 101201.
AB  - Veriflow Campylobacter is a molecular based assay for the presumptive and
      qualitative detection of the most common occurring foodborne Campylobacter
      species: C. jejuni and C. coli. The assay utilizes a PCR detection method coupled
      with a rapid, visual, flow-based assay that develops in 3 min post PCR
      amplification and requires only 24 h of non-specialized enrichment for maximum
      sensitivity. The Veriflow Campylobacter system eliminates the need for
      microaerobic chambers, gel electrophoresis or fluorophore based detection of
      target amplification, and does not require complex data analysis. This
      Performance Tested Method validation study demonstrated the ability of the
      Veriflow method to detect naturally occurring Campylobacterfrom chicken carcass
      rinsates. In the reference comparison study, Chi-square and probability of
      detection analyses of two unpaired studies indicated that there was no
      significant difference between the Veriflow Campylobacter method and the U.S.
      Department of Agriculture (USDA)/Food Safety and Inspection Service (FSIS)
      reference method. There was no indication of false positive or false negative
      detection in the reference comparison study, and all 50 C. jejuni and C. coli
      strains were detected, while 35 nonspecific organisms were undetected in the
      exclusivity/ inclusivity study. The study results show that Veriflow
      Campylobacter is a sensitive, selective and robust assay for the detection of C.
      jejuni and C. coli in chicken carcass rinsates.

PMID- 25051631
TI  - Evaluation of the ANSR for Salmonella assay for identification of Salmonella spp.
      from colony picks from selective/differential agar media: first action 2013.14.
AB  - A collaborative study was conducted to evaluate performance of the ANSR for
      Salmonella assay for identification of Salmonella spp. from colony picks taken
      from selective/differential agar media. The ANSR Salmonella assay is an
      isothermal nucleic acid amplification test based on the nicking enzyme
      amplification reaction chemistry. The test can be completed in less than 40 min
      including sample preparation. A total of 18 laboratories representing industry,
      government, academic, and commercial testing laboratories participated in the
      study. Each collaborator tested up to 84 samples, comprised of colony picks of
      six Salmonella spp. and six non-salmonellae taken from six selective/differential
      agar media as well as tryptic soy agar. A total of 1441 analyses were performed,
      1416 of which gave the correct identification, for overall accuracy of 98.3%. For
      identification of Salmonella spp., 755 of 756 tests (99.9%) produced the correct
      result. For identification of non-salmonellae as such, 661 of 685 assays (96.5%)
      produced the correct result. Of the 18 laboratories, 15 produced data sets with
      99-100% accuracy. The majority of false-positive results were clustered in three
      laboratories; analysis of raw data suggests procedural difficulties in at least
      two cases, which may explain the atypical data from these collaborators. The ANSR
      Salmonella assay can be used as a rapid, accurate adjunct or alternative to
      biochemical testing for identification of presumptive Salmonella spp. isolates.

PMID- 25051632
TI  - Dai nippon printing co., ltd, Medi-Ca AC for enumeration of aerobic bacteria.
      Performance tested method 041302.
AB  - A ready-made dry medium method for aerobic count, the MediCa AC method, was
      compared to the AOAC Official Method 966.23, Microbiological Methods, for seven
      different heat-processed meat matrixes: cooked roast beef, Chinese barbecued pork
      (barbecued pork seasoned with honey-based sauce), bacon, cooked ham, frankfurter
      (made from beef and pork), and boiled and cooked pork sausage. The 95% confidence
      interval for the mean difference between the two methods at each contamination
      level for each matrix fell within the range of -0.50 to 0.50, and no statistical
      difference was observed at all three contamination levels for five matrixes.
      These results demonstrate that the Medi-Ca AC method is a reasonable alternative
      to the AOAC 966.23 method for cooked meat products.

PMID- 25051633
TI  - InstantLabs Listeria species food safety kit. Performance tested methods 041304.
AB  - The InstantLabs Listeria Species Food SafetyKitwas validated against the
      International Organization for Standardization (ISO) reference method 11290-1 for
      the detection of Listeria monocytogenes and other Listeria species. The matrixes
      (stainless steel, sealed concrete, cheddar cheese, raw shrimp, and hot dogs) were
      inoculated with approximately 1 CFU/test portion of various Listeria species to
      generate fractional positives (5-15) in 20 inoculated samples. Enrichments were
      also fractionally inoculated with L. monocytogenes for side-by-side testing of
      the InstantLabs Listeria monocytogenes Food Safety Kit. Stainless steel and
      sealed concrete samples were validated using 4 x 4" and 1 x 1" test areas,
      respectively, and enriched in Buffered Listeria Enrichment Broth (BLEB) at 35 +/-
      1 degrees C for 22-28 h. All food samples were tested at 25 g or 25 mL and
      enriched in BLEB at 35 +/- 1 degrees C for 24-28 h. All samples were confirmed
      using the ISO reference method, regardless of initial screen result. The
      InstantLabs test method performed as well as or better than the reference method
      for the detection of Listeria species on stainless steel, sealed concrete,
      cheddar cheese, raw shrimp, and hot dogs. Inclusivity and exclusivity testing
      revealed no false negatives and no false positives among the 80 Listeria species
      and 30 non-Listeria species examined. The method was shown to be robust when
      variations were introduced to the enrichment time, the volume for DNA extraction,
      and the heat block time (data not shown).

PMID- 25051634
TI  - InstantLabs Listeria monocytogenes food safety kit. Performance tested method
      051304.
AB  - The InstantLabs Listeria monocytogenes Food Safety Kit was validated against the
      International Organization for Standardization (ISO) reference method 11290-1 for
      the detection of Listeria monocytogenes and other Listeria species. The matrixes
      (stainless steel, sealed concrete, ice cream, whole milk, cheddar cheese, raw
      shrimp, hot dogs, deli turkey, and lettuce) were inoculated with approximately 1
      CFU/test portion of L. monocytogenes to generate fractional positives (5-15) in
      20 inoculated samples. Enrichments were also fractionally inoculated with L.
      grayii for side-by-side testing of the Listeria Species Food Safety Kit.
      Stainless steel and sealed concrete samples were validated using 4 x 4" and 1 x 1
      " test areas, respectively, and enriched in Buffered Listeria Enrichment Broth
      (BLEB) at 35 +/- 1degreesC for 22-28 h. All food samples were tested at 25 g and
      enriched in BLEB at 35 +/- 1 degreesC for 24-28 h. All samples were confirmed
      using the ISO reference method, regardless of initial screen result. The
      InstantLabs test method performed as well as or better than the reference method
      for the detection of L. monocytogenes on stainless steel and sealed concrete and
      in ice cream, whole milk, cheddar cheese, raw shrimp, hot dogs, deli turkey, and
      lettuce. Inclusivity and exclusivity testing revealed no false negatives and no
      false positives among the 50 L. monocytogenes serovars and 30 non-L.
      monocytogenes species examined. The method was shown to be robust when the
      enrichment times, volumes for DNA extraction, and heat block times were varied.

PMID- 25051635
TI  - Staphylococcal enterotoxin B-specific electrochemiluminescence and lateral flow
      device assays cross-react with staphylococcal enterotoxin D.
AB  - Guam school children and faculty members experienced symptoms of vomiting,
      nausea, abdominal cramps, and diarrhea shortly after eating breakfast prepared by
      contracted caterers. The first illness was reported within an hour after
      breakfast, affecting 295 students and two faculty members. Local hospitals
      treated 130 people, and 61 were admitted for further treatment. Reported symptoms
      were consistent with staphylococcal food poisoning. Initial food testing using a
      lateral flow device and electrochemiluminescence method incorrectly implicated
      staphylococcal enterotoxin B as the causative agent, prompting partial activation
      of Guam's Emergency Response Center. Traditional ELISAs proved that the food
      poisoning agent was staphylococcal enterotoxin D. More specific and sensitive
      assays would have alleviated the issues and confusion that surrounded the
      reporting and investigation of this outbreak.

PMID- 25051636
TI  - Detection of Salmonella species in a variety of foods by the DuPont Bax system
      real-time PCR assay for Salmonella: first action 2013.02.
AB  - A multilaboratory study was conducted to evaluate the ability of the DuPont BAX
      System Real-Time PCR Assay for Salmonella to detect the target species in a
      variety of foods and environmental surfaces. Internal validation studies were
      performed by DuPont Nutrition & Health on 24 different sample types to
      demonstrate the reliability of the test method among a wide variety of sample
      types. Two of these matrixes-pork and turkey frankfurters and pasteurized, not
      from-concentrate orange juice without pulp-were each evaluated in 14 independent
      laboratories as part of the collaborative study to demonstrate repeatability and
      reproducibility of the internal laboratory results independent of the end user.
      Frankfurter samples were evaluated against the U.S. Department of Agriculture,
      Food Safety and Inspection Service reference method as a paired study, while
      orange juice samples were evaluated against the U.S. Food and Drug Administration
      reference method as an unpaired study, using a proprietary media for the test
      method. Samples tested in this study were artificially inoculated with a
      Salmonella strain at levels expected to produce low (0.2-2.0 CFU/test portion) or
      high (5 CFU/test portion) spike levels on the day of analysis. For each matrix,
      the collaborative study failed to show a statistically significant difference
      between the candidate method and the reference method using the probability of
      detection statistical model.

PMID- 25051637
TI  - Determination of ochratoxin A in Capsicum spp. (paprika and chili) by
      immunoaffinity column cleanup and liquid chromatography: collaborative study.
AB  - A method validation study for the determination of ochratoxin A in Capsicum spp.
      (paprika and chili) was conducted according to the International Union of Pure
      and Applied Chemistry harmonized protocol. The method is based on the extraction
      of samples with aqueous methanol, followed by an immunoaffinity column cleanup.
      The determination is carried out by RP-HPLC coupled with a fluorescence detector.
      The study involved 21 participants representing a cross-section of research,
      private, and official control laboratories from 14 European Union (EU) Member
      States and Singapore. Mean recoveries reported ranged from 83.7 to 87.5%. The RSD
      for repeatability (RSDr) ranged from 1.7 to 14.3%. The RSD for reproducibility
      (RSDR) ranged from 9.1 to 27.5%, reflecting HorRat values from 0.4 to 1.3
      according to the Horwitz function modified by Thompson. The correction for
      recovery of results from naturally contaminated samples further improved the
      reproducibility of the method. The method showed acceptable within-laboratory and
      between-laboratory precision for each matrix, and it conforms to requirements set
      by current EU legislation.

PMID- 25051638
TI  - Determination of ochratoxin A in cocoa beans using immunoaffinity column cleanup
      with high-performance liquid chromatography.
AB  - A method was developed and validated for the determination of ochratoxin A (OTA),
      a fungal metabolite, in cocoa beans of high fat content. The sample was extracted
      by blending with a 1% sodium bicarbonate solution (pH 10) followed by
      ultrasonication, and the sample was defatted by treatment with a flocculant. The
      defatted sample was purified using immunoaffinity column chromatography, and OTA
      was detected using HPLC with fluorescence detection. The method was fully
      optimized, validated, and quality controlled using spike recovery analyses, with
      recoveries of 89-105% over spiking ranges of 320-2.5 ng/g with CV of analyses
      generally <10% over 4 consecutive years and an LOQ of 0.66 ng/g in cocoa bean
      samples. This method overcomes the problems posed by the high fat contents of
      cocoa and chocolate samples with a high degree of reliability.

PMID- 25051639
TI  - Screening multimycotoxins in food-grade gums by stable isotope dilution and
      liquid chromatography/tandem mass spectrometry.
AB  - Stable isotope dilution with LC/MSIMS was used to determine the following 11
      mycotoxins in food grade gums: aflatoxins B1, B2, G1, and G2; deoxynivalenol;
      fumonisins B1, B2, and B3; ochratoxin A; T-2 toxin; and zearalenone. Samples were
      fortified with 11 [13C]-uniformly labeled internal standard ([13C]-IS) mycotoxins
      that corresponded to the 11 target mycotoxins and extracted by acetonitrile-water
      (4 + 1, v/v), followed by LC/MS/MS analysis. Mycotoxins were quantitated with the
      fortified [13C]-IS in each sample. The average recoveries of aflatoxins B1, B2,
      G1, and G2 (1, 5, and 25 microg/kg); deoxynivalenol and fumonisins B1, B2, and B3
      (25, 100, and 500 microg/kg); and ochratoxin A, T-2 toxin, and zearalenone (10,
      50, and 250 microg/kg) ranged from 84 to 117% with RSDs less than 20%. Method
      dependent LOQs were from 0.1 (aflatoxin B1) to 25 microg/kg (fumonisin B3). Among
      20 market samples, aflatoxin B1 (< LOQ) was detected in a Guar gum and a
      Tragacanth gum, and zearalenone (6 +/- 0.6 microg/kg) was detected in a Xanthan
      gum. The detected mycotoxins were further confirmed by comparing their enhanced
      product ion spectra to those of reference standards. The single laboratory
      validated stable isotope dilution and LC/MSIMS method provides sufficient
      selectivity, sensitivity, accuracy, and reproducibility with a simple sample
      preparation to screen the 11 mycotoxins in gums.

PMID- 25051640
TI  - Modification to AOAC official methods 2009.01 and 2011.25 to allow for minor
      overestimation of low molecular weight soluble dietary fiber in samples
      containing starch.
AB  - AOAC Official Methods 2009.01 and 2011.25 have been modified to allow removal of
      resistant maltodextrins produced on hydrolysis of various starches by the
      combination of pancreatic alpha-amylase and amyloglucosidase (AMG) used in these
      assay procedures. The major resistant maltodextrin, 6(3),6(5)-di-alpha-D-glucosyl
      maltopentaose, is highly resistant to hydrolysis by microbial alpha-glucosidases,
      isoamylase, pullulanase, pancreatic, bacterial and fungal alpha-amylase and AMG.
      However, this oligosaccharide is hydrolyzed by the mucosal alpha-glucosidase
      complex of the pig small intestine (which is similar to the human small
      intestine), and thus must be removed in the analytical procedure. Hydrolysis of
      these oligosaccharides has been by incubation with a high concentration of a
      purified AMG at 60 degrees C. This incubation results in no hydrolysis or loss of
      other resistant oligosaccharides such as FOS, GOS, XOS, resistant maltodextrins
      (e.g., Fibersol 2) or polydextrose. The effect of this additional incubation with
      AMG on the measured level of low molecular weight soluble dietary fiber (SDFS)
      and of total dietary fiber in a broad range of samples is reported. Results from
      this study demonstrate that the proposed modification can be used with confidence
      in the measurement of dietary fiber.

PMID- 25051641
TI  - A rapid method for quantifying chlorogenic acid levels in potato samples.
AB  - Chlorogenic acids (CGA) are found in many plant-derived foodstuffs and are
      claimed to have various beneficial effects on human health. Potatoes are a major
      component of the human diet and contain CGA, but little is known about their
      abundance in these important tubers. We therefore used a rapid, sensitive, and
      selective method for quantifying CGAs in food using ultra-high performance LC
      diode array detection (UHPLC-DAD). We also established an optimized sample
      preparation protocol based on ultrafiltration and used these techniques to
      quantify the CGA contents of selected potato varieties (fresh and after storage)
      and potato products. The measured CGA concentrations in potato skins were 37-636
      mg/100 g dry weight (DW) and were three to four times greater than those in the
      flesh. Storage reduced the CGA levels in potatoes by up to 81%. The studied
      potato purees contained 4-11 mg CGA/100 g DW. In addition, the quinic acid
      contents of potato flesh (11-95 mg/100 g DW) and puree (11-22 mg/100 g DW) were
      measured using stable isotope dilution analysis. None of the tested samples
      contained caffeic acid. Overall, our results demonstrated that the UHPLC-DAD
      method can be used to rapidly quantify CGA levels in potatoes and related food
      products.

PMID- 25051642
TI  - New microbiological assay for determination of caspofungin in the presence of its
      degradation products and its measurement uncertainty.
AB  - Caspofungin is an echinocandin antifungal used in the treatment of invasive
      fungal infections. Several methods have been reported for the quantitative
      analysis of echinocandins; however, there is no microbiological assay for
      determination of caspofungin potency in the presence of its degradation products.
      This study aimed to develop and validate a microbiological method for
      quantitative analysis of caspofungin in lyophilized powder, evaluate the
      stability, and determinate the degradation kinetics of the drug when the finished
      product is submitted to heat stress. A procedure was established to estimate
      measurement uncertainty for routine analysis. The validation was performed as
      recommended in the current official guidelines. The agar diffusion method is
      based on the inhibitory effect of caspofungin on Candida albicans. Results showed
      selectivity, linearity, precision, and accuracy of the method. Statistical
      analysis demonstrated that method is linear (in the range 2.5 to 16 microg/mL, y=
      15.73 + 6.4x, r2 = 0.9965), precise (intermediate precision: 2.54%), and accurate
      (recovery range: 95.01-102.46%). The proposed method allowed evaluation of the
      thermal stability of the drug at 80 degreesC for 120 min and determination of
      first order degradation kinetics. The variability of inhibition zone sizes was
      the most important source of uncertainty at about 87% of the overall uncertainty
      (103.0+/-1.7%). These results show that the proposed method is applicable to
      routine laboratory testing, and is sensitive to thermal degradation of
      caspofungin.

PMID- 25051643
TI  - Interlaboratory study of immunochromatography for the rapid determination of
      cadmium concentrations in cereals and soybeans.
AB  - Cadmium (Cd) is one of the most toxic heavy metals to humans. To prevent the
      distribution of Cd-contaminated food, a simple and quick on-site test for
      measuring Cd concentrations in agricultural products is needed. Recently, an
      immunochromatography kit developed for determining Cd in rice was reported to be
      useful for determining Cd in many other crops. We conducted an interlaboratory
      study to evaluate the kit for determining Cd in cereals (wheat and rice) and
      soybeans. Ten test materials were used, and 12 test samples including two sets of
      blind duplicates were distributed to 12 laboratories in Japan. The Cd recoveries
      (relative to certified values or values determined by inductively coupled plasma
      MS) from all test materials were 84.6-125.1%. Repeatability RSD values of the
      test materials ranged from 8.8 to 14.8%. Reproducibility RSD values ranged from
      13.4 to 27.6%, averaging 21.3%. The Horwitz ratio ranged from 0.61 to 1.36. The
      reproducibility was within the range of ELISA results for measuring toxins and
      allergens in food. Our results indicated that the kit was an inexpensive,
      reliable tool for quick and easy on-site determination of Cd in cereals and
      soybeans.

PMID- 25051644
TI  - Synchronous spectrofluorimetric determination of naphthalene in water samples
      using mixed micellar medium.
AB  - A mixed micellar medium of sodium dodecyl sulfate and Pluronic F-127 was used to
      enhance the fluorescence of naphthalene and to obtain lower LODs. The method was
      based upon measuring the first-derivative synchronous fluorescence spectrum of
      naphthalene by using a mixed micellar medium at a constant wavelength difference
      delta lambda = 60 nm, where a greater fluorescence enhancement was observed if
      compared to using a single surfactant separately. A linear fluorimetric
      calibration curve was obtained for naphthalene in a concentration range of 10-200
      ng/mL. The LOD was 7.13 ng/mL, which is well below the health advisory limit for
      naphthalene in drinking water as suggested by the U.S. Environmental Protection
      Agency. The method can be easily adopted for determination of naphthalene in
      aqueous media including tap water and river water. The recoveries obtained were
      95.979-115.645%. The proposed method was validated according to International
      Conference on Harmonization guidelines and successfully applied to determine
      naphthalene in real life water samples from different sources.

PMID- 25051645
TI  - Determination of abamectin residues in edible oils by high-performance liquid
      chromatography with fluorescence detection.
AB  - A rapid and simple HPLC-fluorescence detection method has been developed for the
      determination of abamectin residues in edible oil. Residues are extracted with
      acetonitrile and by vortexing and then directly derivatized with no need for a
      time-consuming cleanup step. Trifluoroacetic anhydride and N-methylimidazole were
      used as derivatizing agents of abamectin. Abamectin was detected and quantitated
      with fluorescence detection (excitation: 365 nm; emission: 475 nm), and methanol
      was used as the mobile phase. The LOD was 0.001 mg/kg and the LOQ was 0.003
      mg/kg. The recoveries ranged from 86 to 100.4% with satisfactory precision (RSD <
      10.1%). This method proved to be sensitive, environmentally friendly, time
      saving, and efficient.

PMID- 25051646
TI  - Separation and preconcentration of trace amounts of rhodium using a dispersive
      liquid-liquid microextraction method and its determination by flame atomic
      absorption spectrometry.
AB  - A sensitive and selective method for the determination of low levels of rhodium
      (Rh) in environmental samples is needed. In the proposed method, an extracting
      solvent with a lower toxicity and density than the other solvents typically used
      in dispersive liquid-liquid microextraction was used to extract trace amounts of
      Rh from aqueous samples. Rh ions were complexed with 1-(2-pyridylazo)-2-naphthol
      in the pH range of 3.2-4.7 and extracted with dispersive liquid-liquid
      microextraction. The type and volume of the extracting solvent and dispersive
      solvent, centrifugation time, pH, amount of the chelating agent, and sample ionic
      strength were carefully studied. Under the optimal conditions, the LOD and RSD
      were 0.36 ng/mL (3Sb/m, n = 7) and +/-2.0% (n = 7), respectively. The calibration
      curve was linear in the range of 4.0-800 ng/mL. The method was applied to the
      determination of Rh in well and tap water, and spiked recoveries were in the
      range of 96-103.7%.

PMID- 25051648
TI  - The use of dispersive pipet extraction (DPX) tips for the sample cleanup of
      apples, pears, and oranges in the analysis of formetanate HCI.
AB  - The U.S. Environmental Protection Agency Analytical Chemistry Laboratory
      evaluated the effectiveness of dispersive pipet extraction (DPX) tip cleanup and
      compared the results with the Quick, Easy, Cheap, Effective, Rugged, and Safe
      dispersive tube cleanup for the sample preparation of three different fruit
      matrixes analyzed for formetanate HCI (FHCI). Using LC/MS/MS, the target LOD and
      the LOQ achieved for FHCI with dispersive tubes, 0.1 and 0.3 ng/g, respectively,
      were similar to the DPX tip sample cleanup. Recoveries at the LOQ ranged from 94
      to 109%. A set of 20-40 samples could be prepared in one working day by one
      chemist.

PMID- 25051647
TI  - Determination of forchlorfenuron in fruits by solid phase or QuECHERS extraction
      and LC-UV or LC/MS/MS.
AB  - Forchlorfenuron, N-(2-chloro-4-pyridinyl)-N'-phenylurea, is a plant growth
      regulator used to increase the size of kiwifruit, apples, table grapes, and
      peaches and to promote increased yields of potatoes, rice, and wheat. This study
      reports the comparison of the performances of two extraction methods [Quick,
      Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) and SPE] and two analytical
      methods (LC-UV and a LC/MS/MS) when determining forchlorfenuron in apples, kiwis,
      and grapes. Both extraction methods gave recoveries of forchlorfenuron from
      fruits >70%. The QuEChERS method was cheaper, safer, and less time-consuming than
      the SPE method and can be recommended for routine analysis. The LOQ was 2 and 10
      microg/kg for the LC/MS/MS and LC-UV analysis, respectively. The LOD was 1 and 5
      microg/kg for the LC/MS/MS and LC-UV analysis, respectively. The sensitivity of
      the LC-UV analysis was adequate to measure residue levels five times lower than
      the maximum residue limit (MRL) of the product. The QuEChERS and SPE methods were
      applied to monitoring the persistence of forchlorfenuron in field-treated kiwis,
      and it was found that the residual concentration was already much lower than the
      MRL 7 days after treatment.

PMID- 25051649
TI  - Speciation and determination of inorganic arsenic in rice using liquid
      chromatography-inductively coupled plasma/ mass spectrometry: collaborative
      study.
AB  - An analytical method to speciate two inorganic As forms [arsenite, As(lll) and
      arsenate, As(V)] in indica and japonica types of rice (both husked and polished)
      and determine the inorganic As concentration as the sum of these two was
      internationally validated. The method can additionally determine two organic As
      compounds, monomethylarsonic acid and dimethylarsinic acid, in rice as separate
      LC peaks. The method is based on LC separation and inductively coupled plasma
      (ICP)-MS detection. The method was evaluated through the International Union of
      Pure and Applied Chemistry/lnternational Organization for Standardization/AOAC
      harmonized protocol. Sixteen laboratories from four countries participated in the
      study, and 13 laboratories returned valid data. Twenty test portions of 10 blind
      duplicates of indica and japonica type rice samples (both husked and polished)
      were used in this study. Repeatability RSD (RSDr) and reproducibility RSD (RSDR)
      were calculated at five concentrations of total inorganic As between 0.03 and
      0.68 mg/kg. The RSDr was in a range of 3.8 to 7.7% and the RSDR was in a range of
      10 to 36%. These performance characteristics were found to be sufficient for
      determination of inorganic As at or higher than 0.03 mg/kg. Applicability of the
      method was estimated to be in a range of 0.02-2.0 mg/kg.

PMID- 25051650
TI  - Speciation and preservation of Cr VI and Cr III in finished drinking water
      matrixes using collision cell ion chromatography-inductively coupled plasma-mass
      spectrometry.
AB  - The polyatomic background at the major isotope of Cr was evaluated as a function
      of collision cell gas flow rate using three different mobile phases. The
      stability of Cr VIwas evaluated as a function of solution pH by fortifying
      samples with enriched 53Cr VI. The 53Cr VI recovery was > or =95% at pH 7.8, but
      by pH 6.2 a significant amount of the enriched spike was recovered as 53Cr III
      EDTA. The instability of Cr III at pHs above 7.8 required that Cr III be chelated
      prior to speciation. The concentration of EDTA was optimized by evaluating Cr III
      recoveries in six finished drinking waters, a U.S. Geological Survey reference
      water, and a challenge water fortified with competing matrix cations. If the Cr
      III was allowed to precipitate (characteristic of shipping a sample without field
      preservation), acceptable recoveries of Cr III required the sample to be heated
      to 70 degrees C in 10 mM EDTA to quantitatively produce the Cr III-EDTA complex.
      The overall preservation/speciation approach was evaluated using an enriched 53Cr
      VI and natural Cr III in seven drinking water matrixes over a 46 day period. A
      linear least squares analysis was performed on each water, and the corresponding
      P-values were estimated. The method detection limits for Cr III-EDTA and Cr VI
      were 0.06 and 0.1 pglL, respectively.

PMID- 25051651
TI  - Making the case for a model mental health advance directive statute.
AB  - Acute episodes of mental illness temporarily destroy the capacity required to
      give informed consent and often prevent people from realizing they are sick,
      causing them to refuse intervention. Once a person refuses treatment, the only
      way to obtain care is as an involuntary patient. Even in the midst of acute
      episodes, many people do not meet commitment criteria because they are not likely
      to injure themselves or others and are still able to care for their basic needs.
      Left untreated, the episode will likely spiral out of control. By the time the
      person finally meets strict commitment criteria, devastation has already
      occurred. This Article argues that an individual should have the right to enter a
      Ulysses arrangement, a special type of mental health advance directive that
      authorizes a doctor to administer treatment during a future episode even if the
      episode causes the individual to refuse care. The Uniform Law Commissioners
      enacted the Uniform Health-Care Decisions Act as a model statute to address all
      types of advance health care planning, including planning for mental illness.
      However, the Act focuses on end-of-life care and fails to address many issues
      faced by people with mental illness. For example, the Act does not empower people
      to enter Ulysses arrangements and eliminates writing and witnessing requirements
      that protect against fraud and coercion. This Article recommends that the Uniform
      Law Commissioners adopt a model mental health advance directive statute that
      empowers people to enter Ulysses arrangements and provides safeguards against
      abuse. Appendix A sets forth model provisions.

PMID- 25051652
TI  - Refereeing the public health.
AB  - Between January 2009 and October 2013, 49 states and the District of Columbia
      passed laws focusing on mitigating the consequences of traumatic brain injuries
      (TBIs) in organized youth sports. Using historical, contextual, and empirical
      methods, this Article describes the content, goals, and structure of youth sports
      TBI laws, while hypothesizing about their underlying legislative logic and long
      term public health consequences. The Article's empirical evidence suggests two
      key findings: first, that a dominant interest group, the National Football
      League, helped to define the problem and its associated solutions for the vast
      majority of states, thus curving the legislative story are in favor of its policy
      prescriptions; second, that existing youth sports TBI laws are focused on
      secondary, not primary, prevention, and may thus shift attention away from more
      comprehensive solutions. Finally, the Article explains why such state laws will
      likely fail to substantially resolve the larger untackled problem--significantly
      reducing the overall rate and number of TBIs in youth sports. After explaining
      why existing state youth sports TBI laws fail to accomplish this broader goal,
      the Article queries whether alternative policy or public health measures might
      offer more robust solutions.

PMID- 25051653
TI  - Human research subjects as human research workers.
AB  - Biomedical research involving human subjects has traditionally been treated as a
      unique endeavor, presenting special risks and demanding special protections. But
      in several ways, the regulatory scheme governing human subjects research is
      counter-intuitively less protective than the labor and employment laws applicable
      to many workers. This Article relies on analogical and legal reasoning to
      demonstrate that this should not be the case; in a number of ways, human research
      subjects ought to be fundamentally recast as human research workers. Like other
      workers protected under worklaw, biomedical research subjects often have
      interests that diverge from those in positions of control but little bargaining
      power for change. Bearing these important similarities in mind, the question
      becomes whether there is any good reason to treat subjects and protected workers
      differently as a matter of law. With regard to unrestricted payment, eligibility
      for a minimum wage, compensation for injury, and rights to engage in concerted
      activity, the answer is no and human subjects regulations ought to be revised
      accordingly.

PMID- 25051654
TI  - Criminal law and HIV testing: empirical analysis of how at-risk individuals
      respond to the law.
AB  - This Note assesses the effect of laws that specifically criminalize behaviors
      that expose others to the human immunodeficiency virus (HIV). This Note examines
      the relationship between HIV testing decisions by high-risk individuals and the
      existence of these HIV-specific statutes, as well as the amount of media coverage
      related to them. One of the main reasons public health experts criticize
      criminalization of HIV-exposing behavior is that it may discourage at-risk
      individuals from undergoing HIV testing. This argument, however, remains
      empirically untested to date. This study quantitatively examines whether at-risk
      individuals living in jurisdictions with HIV-specific statutes are less likely to
      report having been tested for HIV in the past year compared to those living in
      jurisdictions without HIV-specific statutes. Regression analysis is conducted
      using data collected in the United States over a seven-year span. The results
      show that at-risk individuals residing in states with HIV-specific statutes are
      no less likely to report having been tested for HIV than those who live in other
      states. However, the number of people who reported that they had been tested for
      HIV is inversely correlated with the frequency of newspaper coverage of
      criminalization of HIV-exposing behavior. These findings imply that at-risk
      individuals' HIV testing is associated with media coverage of criminalizing HIV
      exposing behavior. The negative impact that criminal law has on HIV testing rates
      could be a serious public health threat. Testing is often the initial step in
      public health interventions that most effectively modify the risky behavior of
      HIV-positive individuals. The adverse consequence of criminalization should weigh
      heavily in the design and application of criminal sanctions for HIV-exposing
      behavior. In addition, future research should further explore the relationships
      between criminalization, media coverage of criminalization, and HIV testing
      decisions for a more nuanced understanding of the consequences of
      criminalization.

PMID- 25051655
TI  - [Molecular epidemiology of the Methicillin-resistant Staphylococcus aureus(MRSA)
      by the internal transcribed spacer PCR (ITS-PCR) method and the phage open
      reading frame typing (POT) method].
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative
      bacteria of hospital acquired infection, and should be rapidly identified for
      infection control. For this purpose, in our hospital, the PCR electrophoresis
      patterns of spacer regions (ITS: internal transcribed spacers) (ITS-PCR) are
      combined with a toxigenicity assay to establish a strain identification method
      for outbreak surveillance. In the present study, the usefulness of this method
      was evaluated in comparison with the POT (phage-open reading frame typing)
      method. One hundred MRSA strains isolated from inpatients in our hospital between
      April 2011 and March 2012 were classified into 25 patterns using the ITS-PCR
      method combined with a toxigenicity assay. The strains could be classified into
      46 patterns using the POT method. ITS-PCR type 22 strain producing enterotoxin C
      and toxic shock syndrome toxin-1 could be further classified into 7 patterns
      using the POT method. In the outbreak of the type 22 strain, cross-infection
      could be excluded by additional analysis using the POT method, providing more
      precise information on strain identification. We identified that some strains of
      the same POT type consisted of different ITS-PCR types or toxigenicities.
      Therefore, these results suggest that the combination of ITS-PCR method plus
      toxigenicity assay with POT method may be a useful technique of MRSA typing.

PMID- 25051656
TI  - [A fatal case of septicemia by serotype A:3 Pasteurella multocida in human:
      review of 14 septic cases in Japan].
AB  - We report a case of systemic inflammatory response syndrome (SIRS) due to
      septicemia by Pasteurella multocida (P. multocida) who died three days after on
      admission. A few cases of septicemia by P. multocida were previously reported. In
      particular, capsular serotype analysis and somatic serotype analysis of P.
      multocida in human is very rare. Serotype A:3 P. multocida was identified in a
      diabetic patient with chronic obstructive pulmonary disease (COPD). There was
      high possibility that the isolate has been transmitted from an indoor companion
      dog since the patient had had close contact with the dog for one month. Here we
      discuss our case and 13 human cases of septicemia by P. multocida reported in
      Japan. Four cases from dogs and eleven cases from cats were included in these
      cases. The mortality rate of septicemia by P. multocida was 21.4% (3/14 cases).
      Two out of three cases died were diabetic.

PMID- 25051657
TI  - [Sonographic appearance of benign subcutaneous nodules--including color Doppler
      sonography].
AB  - OBJECTIVE: Color Doppler sonography is used to distinguish malignant from benign
      subcutaneous nodules because many malignant tumors show an increased number of
      vessels. But benign lesions, such as inflammatory epidermal cysts,
      pilomatricomas, palmoplantar fibromatoses show vascular flow signals. We analyze
      diagnostic factors for subcutaneous nodules on the basis of ultrasonographic
      appearance including color Doppler sonography. METHODS: We evaluated with
      sonography 79 subcutaneous nodules in histopathologically proven cases. RESULTS
      AND DISCUSSION: The diagnostic findings for 28 epidermal cysts were increased
      posterior echo(sensitivity 77%, specificity 90%). Vascular flow signals were seen
      in 7 cases(25%). The signals were seen from periphery to adjacent zone of the
      mass. They were accompanied by inflammatory granulation tissues histologically.
      The percentage of blood flow may be related to the percentage of "ruptured"
      epidermal cysts. Pilomatricomas (n = 9) had internal echogenic foci or Doppler
      flow signals, and no posterior enhancement (sensitivity 89%, specificity 78%).
      Seven pilomatricomas showed Doppler flow signals in the mass. The percentage of
      flow signals is explained by the degree of internal echogenic foci because
      remarkable calcium deposits producing posterior acoustic shadowing prevent us
      from flow signals. Palmoplantar fibromatoses (n = 5) were ill-defined margins and
      showed internal vascularity with no posterior enhancement (sensitivity 80%,
      specificity 94%). CONCLUSION: More benign lesions showed vascular flow signals
      than reported previously. We have to diagnose subcutaneous nodules referring to
      not only color Doppler but also gray scale sonography.

PMID- 25051658
TI  - [Molecular-pathological analysis of Helicobacter pylori-associated disorders and
      clinical laboratory testing].
AB  - Helicobacter pylori (H. pylori) infection causes gastro-duodenal diseases and a
      wide variety of non gastrointestinal tract conditions, such as idiopathic
      thrombocytopenic purpura (ITP). Many reports have provided robust evidence for
      understanding the pathogenesis of H. pylori. However, its cell division process
      is little known. H. pylori exhibits marked genetic diversity to survive under
      various stress conditions, leading to the emergence of a variety of clones with
      novel characteristics. In this report, we briefly summarize our results. H.
      pylori urease is essential to live in a low-pH environment. Bacterial motility
      and urea taxisis are also important features for persistent infection. The urease
      is controlled in response to the pH via post translational regulation. Genetic
      rearrangement occurs during persistent infection of an individual's stomach,
      which results in the appearance of a variety of new strains with novel
      characteristics. The cdrA (cell division-related gene A)--dysfunctional strain
      had acquired such novel characteristics: increased viability, long-term survival,
      and tolerance to antibiotics. Furthermore, colonization by a cdrA-dysfunctional
      strain results in decreased IL-8 production and, hence, attenuates the host's
      immunity to cause persistent infection. Among the factors involved in the
      bacterium-host interaction and pathogenesis, we describe the H. pylori CagA,
      BabA, SabA, and SOD. We discovered two H. pylori phages, including a new type of
      spherical phage, which cannot be classified into any existing virus category. The
      phages probably contribute to the evolution and pathogenesis of H. pylori.
      Eradication therapy covered by health insurance was approved for H. pylori
      associated ITP. We reported an extra mechanism, the immunocomplex model
      (platelets, bacterial molecules, and anti H. pylori antibodies), in the
      development of H. pylori associated ITP. On the other hand, increased cases of
      unsuccessful eradication therapy are due to the increased occurrence of drug
      resistant H. pylori. Non-antibiotic substances with anti-H. pylori activity are
      attracting much attention.

PMID- 25051659
TI  - [Companion diagnostics "POTELIGEO TEST IHC/FCM" used with "POTELIGEO"
      (mogamulizumab) for adult T-cell leukemia-lymphoma (ATL) treatment].
AB  - Personalized medicine offers the best treatment for individual patients, it is
      important for an IVD manufacturer to develop companion diagnostics in parallel
      with the development of new drugs through close cooperation with drug companies,
      and supply diagnostics companies with new drugs for physicians and patients. We
      received approval for a premarket approval application (PMA) for two in vitro
      diagnostic ("IVD") reagents, POTELIGEO TEST IHC and POTELIGEO TEST FCM
      ("POTELIGEO TEST"), in March 2012, and subsequently launched POTELIGEO TEST in
      May 2012. POTELIGEO TEST is a companion diagnostic used with POTELIGEO for which
      Kyowa Hakko Kirin has a new drug application (NDA) that was approved in March
      2012, and is designed to help physicians identify appropriate subpopulations of
      adult T-cell leukemia-lymphoma(ATL) patients who are most likely to respond to
      POTELIGEO 20 mg (mogamulizumab) Injection ("POTELIGEO").

PMID- 25051660
TI  - [Diagnostic differences in asthma and chronic obstructive pulmonary disease].
AB  - Although both asthma and chronic obstructive pulmonary disease (COPD) are
      characterized as obstructive lung disease, their pathophysiologies are quite
      different. Characteristics of asthma include chronic airway inflammation, airway
      narrowing with reversibility, and responsiveness of airways. Cough, wheezing, and
      dyspnea and variability in these symptoms are also characteristic features of
      asthma. Because there are no definite diagnostic criteria, multidisciplinary
      consideration is necessary when diagnosing asthma. On the other hand, COPD is
      characterized by persistent airflow limitation which is usually progressive. It
      is associated with noxious particles or gasses, typically cigarette smoking, and
      subsequent chronic inflammation of the airway and lungs. Nonreversible airflow
      limitation is a characteristic feature, and exertional dyspnea, chronic cough,
      and sputum are typical symptoms. Diagnostic criteria are relatively simple: post
      bronchodilator FEV1/FVC < 70%, and no other reason for airflow limitation.
      Recently, overlap syndrome, with features of both asthma and COPD, is drawing
      attention. When treating elderly patients with asthma who have persistent airway
      limitation or patients with COPD who show variability in symptoms and
      reversibility of lung function, the possibility of overlap syndrome should be
      considered. The prevalence of overlap syndrome seems to be high in general
      practice, so the introduction of practical criteria for the diagnosis and a
      proper guide for therapies is expected.

PMID- 25051661
TI  - [Pathophysiology, diagnosis and treatment of cough variant asthma].
AB  - Cough variant asthma (CVA) has been recognized as a precursor of asthma or a pre
      asthmatic state because of the mildly heightened bronchial responsiveness and
      efficacy of bronchodilator therapy. Nevertheless, the accumulating evidence
      indicates that the pathophysiology is different between CVA and bronchial asthma.
      The most fundamental physiologic feature is a heightened cough response to
      methacholine-induced bronchoconstriction in CVA, while this response is rather
      reduced in bronchial asthma. The sensitivity of cough receptors located in the
      superficial layer of the airway wall is normal in CVA as well as bronchial
      asthma, but heightened in atopic cough. The pathologic feature of CVA is
      eosinophilic inflammation of the central to peripheral airway, reflected by
      eosinophilia in induced sputum, biopsied bronchial mucosa, and bronchoalveolar
      lavage fluid. The diagnosis of CVA has been commonly made based on therapeutic
      diagnostic procedures, while pathophysiologic diagnosis is ideal. The reason is
      that measurements of the sensitivity of cough receptors to inhaled capsaicin and
      cough response to induced bronchoconstriction are not possible at most chest
      clinics in the world. The efficacy of a beta2-agonist for a patient's coughing is
      evaluated to make a diagnosis of CVA. When the bronchodilator therapy is judged
      as efficacious, a tentative diagnosis of CVA is made. Then, induction therapy is
      initiated for resolution of the cough. The induction therapy consists of beta2
      agonists, leukotriene receptor antagonists, and inhaled corticosteroids. In some
      patients whose cough does not subside with the therapy, short-burst oral
      corticosteroids (1 to 3 weeks) may be added. If the cough still does not subside
      with the therapy, the patient should be referred to cough specialists. When the
      cough subsides with the induction therapy, long-term management is recommended
      using inhaled corticosteroids, because 30% of patients develop typical bronchial
      asthma within several years. Problems with the therapeutic diagnosis are as
      follows: spontaneous relief of cough leading to a false positive result, and
      resistance to the therapy, leading to a false-negative result. Thus, a
      pathophysiologic diagnostic procedure should be established in the future.

PMID- 25051662
TI  - [Up-to-date COPD treatment].
AB  - The strategy for the treatment and management for COPD has markedly changed. COPD
      has been classified as a chronic respiratory disease characterized by an
      irreversible airflow obstruction, but active therapeutic interventions have not
      been established. However, the development of pharmacological and
      nonpharmacological therapy and the accumulation of clinical evidence have
      improved the situation. The newly developed long-acting muscarinic antagonists
      (LAMA) and beta-agonists (LABA), inhaled corticosteroids (ICS), the combination
      of LABA/LAMA and ICS/LABA, and comprehensive respiratory rehabilitation have
      significantly improved the symptoms such as cough, sputum, and dyspnea, as well
      as exercise tolerance, daily activity, and quality of life, and prevent the
      exacerbation of COPD. Furthermore, LAMA and ICS/LABA can prevent disease
      progression and improve the severity and survival. It has been demonstrated that
      inflammation of the lung in COPD affects the whole body and increases co
      morbidities, which affect the QOL and survival. We should treat co-morbidities
      simultaneously. We should view COPD as a preventable and treatable disease, and
      early, active interventions involving pharmacological and non-pharmacological
      treatments not only improve symptoms, but also reduce disease progression and
      improve the survival of COPD patients.

PMID- 25051663
TI  - [Required education for medical technologists of the next generation--chairmen's
      introductory remarks].
AB  - This symposium is named "Required education for medical technologists of the next
      generation", and is held under the joint sponsorship of the Japanese Association
      of Medical Technology Education. We received lectures by two speakers from the
      clinical field and two speakers from a medical technology educational
      institution. From the perspective of the medical technology education
      institution, we were introduced to education that is actually being provided.
      From the clinical perspective, we were given lectures that concretely discussed
      the necessary role of medical technologists in clinical practice. All of the
      lectures were very interesting and helpful.

PMID- 25051664
TI  - [Education required for next generation of clinical laboratory technicians: from
      perspective of three-year educational institutions].
AB  - Considering the education required for the next generation of clinical laboratory
      technicians in terms of elements necessary for the technicians, it is generally
      important for them to be "needed in the medical field", and the three-year
      educational institutions for training them are expected to nurture technicians
      who can work with "skills of immediate use." Herein, the phrase "skills of
      immediate use" does not simply signify knowledge and techniques, but signifies
      skills including behavior as medical staff. In addition, "growth potential"
      permitting continuous growth with self-education and aspiration for improvement
      after gaining employment is of significance. We refer to the "skills of immediate
      use" and the "growth potential" integrally as "Genba-ryoku(on-site
      capabilities)", and have striven for improvement in those capabilities as a basic
      educational policy of our school. In any period, the medical field needs medical
      staff who can perform greetings, cleaning, etc., as sound practices and who are
      well-mannered. It is my belief that educational institutions have to fulfill
      their mission by nurturing medical staff who possess "toughness to work unaided"
      as well as a "gentle mind."

PMID- 25051665
TI  - [College education for medical technologists of the next generation].
AB  - Medical Technologists (MTs) of the next generation will be expected to: 1)
      perform clinical tests in clinical laboratories as so-called Clinical Laboratory
      Scientists(CLS), 2)research and develop highly advanced reagents, devices, or
      procedures for clinical laboratories, and 3) educate MTs and research in the
      college or university. CLS are required to develop and maintain highly advanced
      medical skills as follows: (1) explaining medical tests and those results to
      patients, (2) evaluating and explaining test results to medical doctors, (3)
      advising medical doctors of laboratory diagnoses, (4) analyzing the patients'
      pathophysiology based on samples with aberrant results, (5) evaluating newly
      developed reagents, devices, or procedures, and (6) promoting the total medical
      cure of patients with specialized skills. In the MT course at Shinshu University,
      to develop the skills necessary to become a CLS before graduation, students
      participate in a number of programs, i.e., freshman seminars, observing the
      clinical laboratory, and basic training for medical tests (first grade), special
      lectures from MTs working in the clinical laboratory (second and third grades),
      examination for clinical practice, 12-week clinical practice, and 15-week
      laboratory research (fourth grade). Several academic members working in a
      clinical laboratory and collaboration with the Department of Clinical Laboratory
      at Shinshu University Hospital are essential to realize the above-mentioned
      course.

PMID- 25051666
TI  - [Occupational neurointoxications: patterns and mechanisms of formation].
AB  - The article covers results of long-standing study of clinical features of
      occupational neurointoxications in late period, and mechanisms underlying nervous
      system disorders in individuals working under long exposure to neurotoxic
      chemicals and in late period of occupational intoxications. With modern
      neurophysiologic, neuropsychologic, immunologic and biochemical diagnostic
      methods, the authors specified early manifestations of occupational disorders.
      Translation patterns of neurointoxications are specified.

PMID- 25051667
TI  - [Cognitive disorders in patients with chronic mercury intoxication].
AB  - To assess severity of cognitive disorders in chronic mercury intoxication, the
      authors performed claster and discrimination analysis of neuropsychologic and
      neurophysiologic research data from workers exposed to mercury during long length
      of service, from patients with early and marked stages of chronic mercurial
      intoxication. Cognitive disorders in chronic mercurial intoxication have three
      severity degrees, in the light degree disorders patients demonstrate lower
      amplitude of cognitive evoked potentials, poor long-term memory and associative
      thinking. Moderate cognitive disorders are characterized by decreased visual,
      long-term memory, concentration of attention, poor optic and spatial gnosis.
      Marked cognitive disorders with chronic mercurial intoxication present with more
      decreased long-term, short-term, picturesque memory, poor intellect, optic and
      spatial gnosis and associative thinking.

PMID- 25051668
TI  - [Pathogenetic aspects of occupationally related disorders of lipid metabolism in
      workers exposed to chemicals].
AB  - The article presents results of lipid metabolism parameters in long-standing
      examinations of workers exposed to toxic chemicals. Findings are pro
      atherosclerotic tendencies that can be considered as occupationally related,
      their pathogenetic mechanisms are specified. Evidences are that irrespective of
      acting toxic factor (mercury, vinyl chloride, complex of toxic chemicals)
      sequence of cholesterol metabolism disorders with pro-atherogenous features in
      workers has common aspects: at first, high-density lipoproteins cholesterol level
      lowers and atherogenicity index increases, then general cholesterol level
      increases, and low-density lipoproteins cholesterol level increases afterwards.
      Peculiarity is that chronic occupational exposure to vinyl chloride and toxic
      combustion products causes very low-density lipoproteins involvement into
      atherogenic process. Lipid metabolism disorders in workers exposed to neurotoxic
      chemicals at work appeared to progress into psycho-neurologic sphere changes, to
      have pro-atherogenic tendency and to cause early atherosclerosis, arterial
      hypertension and ischemic heart disease.

PMID- 25051669
TI  - [Genotype-phenotype characteristics of biochemical markers of endothelial
      dysfunction in patients with chronic mercury intoxication].
AB  - The paper presents data on the frequency of polymorphisms of candidate genes
      involved in the formation of endothelial dysfunction--endothelin-1 (EDN1
      Lys198Asn) and endothelial nitric oxide synthase (NOS3 T786C) together with the
      concentrations of their active products (nitric oxide, endothelin-1) in
      individuals with chronic mercury intoxication. The concentration change of nitric
      oxide and endothelin-1 indicates the presence of endothelial dysfunction in the
      individuals examined. The studied polymorphisms appeared to play a minor role in
      the pathogenesis of endothelial dysfunction in patients with chronic mercury
      intoxication.

PMID- 25051670
TI  - [Risk assessment of health disorders and quality of life in employees of modern
      polyvinyl chloride production].
AB  - The authors analyse changes in exposure load and associated occupational risk,
      health state of workers engaged into contemporary polyvinyl chloride production.
      Consideration covered objective parameters--results of thorough medical
      examinations -and subjective ones--results of quantitative risk evaluation of
      general pathologic syndromes and life quality caused by health state. The latter
      were compared with general working population unexposed to the hazards. Findings
      are statistically significant increase of functional disorders risk connected
      with cardiovascular and nervous diseases. Correlation was found between
      cardiovascular diseases prevalence and exposure chemical load. Statistically
      significant differences were seen in all life quality components between the
      workers groups compared.

PMID- 25051671
TI  - [Neurotoxic effect of toluene on background of prenatal hypoxic brain damage to
      white rats].
AB  - Comparative study covered influence of toluene on behavioral parameters,
      cognitive abilities and brain bioelectric activity in white rats with normal
      embryonic development or with prenatal hypoxia. Prenatal hypoxia was simulated by
      subcutaneous injection of 50 mg/kg sodium nitrite into female white rats on day
      13-14 of gestation. The offspring at the age of 2, 5-3 months was exposed to
      toluene (concentration of 560 mg/m3, 4 hours per day, 5 days per week, over 4
      weeks). After the exposure, the animals were estimated for individual and
      intraspecific behaviour in "open fields and "resident-intruder" tests, for
      cognitive abilities in "radial maze" training, EEG with visual and auditory
      evoked potentials. Acute hypoxia at early stages of organogenesis appeared to be
      burdening factor and to influence consequences of toluene intoxication.

PMID- 25051672
TI  - [The role of neurotrophic factors in formation of vibration disease].
AB  - The authors studied serum levels of neurotrophic factors (brain-derived
      neurotrophic factor BDNF and ciliary neurotrophic factor CNTF) in workers exposed
      to vibration (workers with long length of service and without health disorders
      caused by vibration, patients with occupational limbs polyneuropathy, and
      vibration disease patients). Findings are that occupational vibration induces
      increased BDNF and CNTF serum levels in all groups examined. Increased levels of
      neurotrophic factors at early stages of pathologic process indicate their
      protective action, action of compensatory protective mechanisms. However, high
      levels of BDNF and CNTF in vibration disease may point to neurodestructive
      processes in nervous system.

PMID- 25051673
TI  - [Dynamics of morphofunctional state of central nervous system in white rates
      exposed to vibration].
AB  - The authors presented results of experimental studies assessing influence of
      vibration on white rats. Dynamics of morphologic changes development in brain of
      experimental animals exposed to vibration were shown. Exposure to vibration in
      white rats daily during 4 hours over 15 days causes astrogliosis--compensation
      process in response to brain injury; over 1 month--causes morphologic brain
      changes (vacuoles formation in neuropile, decrease in astroglia cells number);
      over 2 months--causes lower plasticity of brain neurons, preserved astrogliosis;
      over 4 months--causes perivascular edema. Changes in brain bioelectric activity
      indicate stages of pathologic process in central nervous system. Increase in
      vibration exposure duration leads to more severe diffuse pathologic changes in
      brain and local cortical and diencephalic disorders. Exposure to vibration in
      white rats causes increase in general mobility, nonspecific activation of
      behaviour, intense emotional exertion, negative emotional state, but less severe
      effects of vibration were seen in orientative-trying reactions that are inborn,
      inherited forms of behaviour.

PMID- 25051674
TI  - [Assessing and forecasting morbidity of adolescents living in area influenced by
      aluminium production].
AB  - Objective of the study--to forecast morbidity (of respiratory diseases) among
      adolescents via mathematic modelling during primary exploitation of new aluminium
      production (exemplified by Taishet city). Incidence during 2003-2011 of all
      diseases in the adolescents equalled 1129,1 per thousand, of respiratory diseases
      -627,4 per thousand. The mathematic model was designed to reveal role of
      environmental hazards in morbidity formation. According to medium-term forecast
      results, launching the aluminium production plant in East Siberia in 3 years will
      increase by 67% the morbidity with respiratory diseases in the adolescents.

PMID- 25051675
TI  - [Influence of transplantation of autogenic mezenhymal stem cells from the fatty
      tissues on osseogenic process (experimental research)].
AB  - In experiments on 48 rats of line Wistar, divided at 2 groups (first--basic group
      and 2-d group--group of comparison) through the use of morphological method was
      researched influence of mesenchymal stem cells (MSC) inoculated in the area of
      autogenic bone graft from tibia fixed at the surface of the jaw. The animals of
      group of comparison didn't get MSC. Time frames of watching: 21, 60, 120 and 180
      days, 6 rats on the point of experiment in either of the two of the group. Data
      of this research had shown the intensification of bone formation process in the
      basic group of experiment under the action of the inoculation of autogenic MSC
      from adipose tissue, and as consequence of it, in eventual, merge of bone
      formations in a single entity.

PMID- 25051676
TI  - [Leukocyte elastase, alpha 1-proteinase inhibitor and C-reactive protein in
      patients with delayed negativation of serological reactions after treatment of
      early syphilis].
AB  - It was investigated the activity of leukocyte elastase, alpha 1-proteinase
      inhibitor and C-reactive protein in patients with delayed negativation of
      serological reactions after a treatment of syphilis. The patients were divided
      into three subgroups. The first subgroup consisted of patients who did not have
      the signs of non-specific immune system response. Second subgroup consisted of
      patients with clear signs of infection process. The patients this subgroup had
      elevated values of the contents of inflammatory mediators. The remaining patients
      with questionable results were attributed in the third subgroup. The obtained
      results can be of great value to determine further treatment strategy in patients
      with delayed negativation of serological reactions.

PMID- 25051677
TI  - [The changes of plasma levels of soluble TNF-alpha and TNF-R1 ratio is a
      prognostic marker and key element of the stroke pathogenesis].
AB  - The goal of the present study was to investigate the plasma levels of sTNF-alpha,
      sTNF-R1 in acute stroke patients, to study the relation between ones, the
      neurological stroke severity and functional disability. The investigations
      comprised 60 ischemic stroke patients, 25 patients form control group. Plasma
      levels of sTNF-alpha, sTNF-R1 were detected by means of ELISA. The conclusion of
      interaction of sTNF-alpha and tmTNF-R1 increases inflammatory and apoptotic brain
      tissue damage on the first day of stroke is drawn. On the 7-th and 21-st days of
      stroke sTNF-alpha realize a neuroprotective effect. The interaction sTNF-alpha
      and sTNF-R1 blockade of damage expansion. As the result, prognostic significance
      of sTNF-alpha/sTNF-R1 is showed.

PMID- 25051678
TI  - [The influence of glutamate antibodies on the level of neurotransmitter
      monoamines in brain structures of rats with ischemic damage of prefrontal
      cortex].
AB  - Experiments on the model of bilateral photothrombosis in prefrontal cortex showed
      that antibodies to glutamate one-time administered intranasally 1h after ischemic
      damage to the brain cortex lead to decrease of neurodegenerative influence of
      excitatory neurotransmitter after photothrombosis. It was showed the change of
      the level of dopamine, serotonin and their metabolites in hippocampus and
      prefrontal cortex.

PMID- 25051679
TI  - [Elimination of the activating influence of emotional stress on hemostasis mild
      hypothermia action].
AB  - The state of the hemostatic system in the psycho-emotional and hypothermia in
      rats. It is shown that the psycho-emotional impact is accompanied by a
      hypercoagulable. "Clean" effect of hypothermia is characterized by the activation
      of anticoagulation and fibrinolysis. Thus, we have shown that the general
      hypothermia in the aquatic environment has a more pronounced effect on the
      hemostatic system than the psycho-emotional impact.

PMID- 25051680
TI  - [Features of the pharmacokinetics of ceftriaxone during the antiorthostatic
      hypokinesia in rats].
AB  - This study was designed to investigate the effects of simulated microgravity on
      the plasma kinetics of ceftriaxone in rats. Comparative analysis of
      pharmacokinetic parameters in control and experimental groups has revealed the
      influence of antiorthostatic hypokinesia (ANOH) on the pharmacokinetics of
      ceftriaxone. Decreased level of maximum plasma concentration (C(max)) and
      bioavailability of ceftriaxone after single intramuscular (IM) injection were
      revealed in rats with antiorthostatic hypokinesia. The rate of absorption of the
      drug was higher respectively.

PMID- 25051681
TI  - [The role of changes in the subfractional compound of tear fluid in the
      assessment of damaging effect from soft contact lenses and the excimer laser
      ablation of the cornea].
AB  - The method of laser correlation spectroscopy (LCS) was used for the examination
      of the subfractional compound of tear fluid in patients who have been using soft
      contact lens (SCL) for a long period and before and after the excimer laser
      correction with transepithelial photorefractive keratectomy (Trans PRK). Based on
      the analysis of biological material of 141 patients aged from 18 to 33 years old,
      we can conclude that prolonged usage of SCL leads to catabolic processes in
      surface of the anterior segment of the eye and, as a result, to changes in the
      qualitative composition of the tear fluid. The amount of low molecular weight
      fractions and medium weight ingredients increases after transepithelial
      photorefractive keratectomy, which can characterize reparation processes after
      cornea ablation. Based on the results of our study we can conclude that LCS--is
      express analysis, with which we can diagnose and observe the initial changes in
      local metabolism in the anterior segment of the eye, when the objective breaches
      have not seen yet.

PMID- 25051682
TI  - [Effect of the alloxane diabetes on the cardio-vascular system function and lipid
      peroxidation in rats of different genetic strains].
AB  - We have previously shown that the innate increased activity of the NO- system,
      typical for the August rats, increases vulnerability to alloxane diabetes (ALD).
      The purpose of this study was to investigate the effect of ALD on the
      cardiovascular system and lipid peroxidation in rats with different activity of
      NO-system. The August rats and Wistar rats treated with alloxan (125 mg/kg, s/c,
      once) were studied 3.5 months after. In August-ALD the double production
      significantly decreased to a greater extent (by 35%) than in Wistar-ALD (by 17%)
      compared with the control. As in August-ALD and in Wistar-ALD was observed the
      similar fall of the relaxation (-dp/dt) of the left ventricle (by 45-49%), but
      not the contraction rate (+dp/dt). LPO activation in the heart and liver, as well
      as NO-system (level of nitrates and nitrites in the blood plasma) in August rats
      were more pronounced than in Wistar rats. The hsp32 level in August rats fell
      significantly more (by 93% ) than in Wistar rats (by 61%). Pathological changes
      in the microvasculature of the mesostenium were identical in compared rats. Thus,
      more pronounced cardiac dysfunction in August-ALD, compared with Wistar-ALD,
      associated with greater activation of lipid peroxidation and NO-system.

PMID- 25051683
TI  - [Surfactant system of lung in rats with different resistance to stress under
      alloxan diabetes].
AB  - It is shown that the surface active properties of lung under experimental
      diabetes mellitus was decreased on the background of increased LPL content in
      alveolar space. Surfactant changes correlated with the level of glucose,
      glycosylated hemoglobin and 11-oxycorticosteroids in blood. The obtained results
      indicate that the degree of impairment in the pulmonary surfactant system in
      alloxan diabetes depends on the resistance or susceptibility of animals to
      stress.

PMID- 25051684
TI  - [Enzymes of azurophilic neutrophil granules and matrix metalloproteinase-2 as
      markers of the developmental stages of experimental respiratory distress
      syndrome].
AB  - Acute Respiratory Distress Syndrome was reproduced in the non-linear male rats by
      the original method. The animals were injected lysate 45-55 thousand rat
      neutrophils in 0.2 mi 0.9% sodium chloride solution by puncture of the trachea
      (method patented RF). At each stage of syndrome development concentration of
      neutrophil elastase, myeloperoxidase and matrix metalloproteinase-2 in serum and
      bronchoalveolar lavage fluid was determined by ELISA. The increase of the
      concentration of neutrophil elastase and myeloperoxidase in plasma and lavage
      fluid has been shown to be a marker of exudative stage. Proliferative phase is
      marked by high levels of matrix metalloproteinase-2 at a constant content of
      elastase and myeloperoxidase in both liquids. Reduction of matrix
      metalloproteinase-2 concentration in both biological fluids is accompanied by the
      development of fibrotic phase distress syndrome.

PMID- 25051685
TI  - [Pharmacotherapeutical efficiency of the dry extract "Ce-god-5" in liver injury
      induced by CCl4 in white rats].
AB  - It has been established that the complex plant remedy "Ce-god-5" possesses the
      marked hepatoprotective effect in liver injury induced by CCl4 in white rats. The
      ability to inhibit the processes of lipid peroxidation and stimulate antioxidant
      system of the body is a basic mechanism of hepatoprotective activity of "Ce-god
      5".

PMID- 25051686
TI  - [Evolutionary admonition: allergy].
AB  - The paper concerns phylogeny development of allergic reactivity, the most
      probable antecedents of allergic IgE antibodies, high affinity IgE receptor
      (Fc(epsilon)RI), presents comparative character of IgE - Fc(epsilon)RI and IgY-
      CHIR-AB1 interactions. The paper has given an insight of allergy as evolutionary
      selected reactivity for highly organized animals. This reactivity is directed to
      organization of allergen-specific inflammation and serves as biologically
      expedient, high-specific and high-sensitive reaction in response to allergen
      entering into the organism because of barrier tissue dysfunction. Such insight
      has raised a question on consequences of thoroughgoing allergy reactivity
      elimination for highly organized animals and their posterity.

PMID- 25051687
TI  - [Significance of GABA in pain syndrome pathogenes].
AB  - The article presents a data on structural and functional organization of GABA
      ergic system of brain and the role GABA in mechanisms of the pathologic pain.

PMID- 25051688
TI  - [Agonists of opioid receptors may aggravate ischemic and reperfusion damages of
      the heart].
AB  - Authors analyzed articles that opioids may aggravate ischemic and reperfusion
      damages of the heart but the opioid receptor antagonists may prevent these
      damages. Authors concluded the it is existed opioid receptor pool an activation
      of its decreases cardiac tolerance to an impact of ischemia-reperfusion.

PMID- 25051689
TI  - [The syndrome of chronic inflammation of adipose tissue].
AB  - The pathogenetic role of adipose tissue chronic inflammation syndrome in
      development of atherosclerosis, type II diabetes, metabolic syndrome and
      hypertension is being discussed.

PMID- 25051690
TI  - [Dual role of photosensibilizator merocyanine 540 as a bactericidal agent and
      immune reaction regulator].
AB  - AIM: Develop conditions for inactivation of staphylococcus by using
      photosensibilizator merocyanine 540 (MC540) for the production of antigenic
      preparation (AP). Study some of immune reactions to AP and the possibility of
      regulation of DTH reaction to AP under the effect of MC540. MATERIALS AND
      METHODS: Merocyanine 540 (MC540, Sigma-Aldrich, Switzerland) is used in the
      study. MC540 and Staphylococcus aureus, strain 78 (Sa78) were irradiated by light
      of a mercury-quartz lamp DRSH-250 (Zelenograd). C56BL/6 line mice were immunized
      once by subcutaneous administration of AP. DTH reaction was tested 7 days after
      the immunization. Functional activity of peritoneal exudate macrophages was
      determined 1 and 9 days after the immunization. Immune modulating effect of MC540
      in DTH was determined after its per os administration to mice 1 hour after AP
      sensibilization. RESULTS: In order to obtain AP, S. aureus suspension at the
      concentration of 2.5 x 10(7) CFU/ml in 25 microM MC540 solution and 0.25 M NaCl
      solution were exposed to irradiation for 5 minutes. During DTH reaction induction
      its intensity dependence on AP dose was revealed. A persistent increase of a
      lysosomatic enzyme cathepsin D in macrophages of peritoneal exudate after a
      single administration of AP was noted. During MC540 irradiation an accumulation
      of photoproducts that have a pronounced immune suppression effect in DTH reaction
      had a dose-dependent character. CONCLUSION: Use of saline allows to increase
      bactericidal potential of a photosensibilizator (PS). However during therapy of
      localized forms of infection a possible immune modulating effect of PS on macro
      organism should be considered. By varying PS dose and irradiation time not only
      maximum bactericidal effect can be achieved but also regulation of inflammatory
      reactions in the area of PS effect can be ensured.

PMID- 25051691
TI  - [Comparative resistance of typical and genetically altered Vibrio cholerae biovar
      El Tor strains to the effect of unfavorable environmental factors].
AB  - AIM: Carry out comparative analysis of survival of typical strains and
      genovariants of V. cholerae biovar El Tor imported in different years to the
      territory of Russian Federation, in the absence of nutrients and under the
      conditions of temperature stress. MATERIALS AND METHODS: 24 V. cholerae biovar El
      Tor strains isolated in 1970 - 2011 were studied, 8 of those were typical
      isolates and 16--genetically altered variants. Strain survival was studied in
      0.9% sodium chloride solution and autoclaved river water at various temperature
      modes (5, 25, 37 and 42 degrees C). Protein composition and exopolysaccharide
      production were determined by electrophoresis method by U.K. Laemmli. RESULTS:
      Genovariants as well as typical strains were shown to be able to exist for a long
      time (up to 5 months) in the absence of nutrients at the temperature of 25
      degrees C. However, unlike typical eltor vibrios, genovariants were more
      resistant to temperature stress. As a result of adaptation to high temperature
      (42 degrees C) biosynthesis of porin proteins of outer membrane OmpU and/or OmpT
      is increased in genovariant cells, and at lower temperatures (5 degrees C)-
      exopolysaccharide. CONCLUSION: V. cholerae biovar El Tor genovariants are able to
      adapt to temperature change better, that may facilitate their higher survival in
      the environment.

PMID- 25051692
TI  - [Colonization properties of opportunistic bacteria isolated from children with
      pneumonia].
AB  - AIM: Evaluation of phenotypes and pathogenicity factors of 476 opportunistic
      bacteria isolated from respiratory samples of 973 children with community
      acquired pneumonia and 36 children without respiratory infection symptoms.
      MATERIALS AND METHODS: Quantitative method of tracheal aspirate and
      nasopharyngeal swab seeding into certified nutrient media was used,
      identification was carried out according to standard techniques. RESULTS:
      Adhesive, "anti-interferon", anti-lysozyme and inherent bactericidal activity of
      Escherichia coli and Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas
      aeruginosa and Acinetobacter spp. were established to ensure in combination with
      known aggression factors their colonization advantage compared with other
      pneumopathogens. Adhesion indexes of Gram-negative bacteria lower than 2.5 are
      shown as markers of invasive strains. Anti-lysozyme activity level lower than
      2.14 microg/ml and lack of "anti-interferon" activity characterize non-invasive
      opportunistic bacteria strains. CONCLUSION: The detected phenotypic features of
      opportunistic bacteria may be used in clinical practice for evaluatio of
      etiologic importance of microorganisms isolated from tracheal aspirate in
      pneumonia patients.

PMID- 25051693
TI  - [Measurement of genital mycoplasma concentration by using a microbiological and
      molecular-biological methods].
AB  - AIM: Establishment of ratios that would allow to execute recalculation of
      mycoplasma concentration from CFU/ml and/or CCU/ml into units obtained during PCR
      analysis--geq/ml. MATERIALS AND METHODS: Pure cultures of Mycoplasma hominis,
      Ureaplasma parvum and Ureaplasma urealyticum were studied by cultural and
      molecular-biological methods with quantitative evaluation. Studies of initial
      cultures as well as series of 10-fold dilutions were carried out. 32 experiments
      in total were carried out. RESULTS: Ratio between geq/ml and CFU/ml for M.
      hominis was 3.5; geq/ ml and CCU/ml ratio--4.4. Ratio between geq/ml and CCU/ml
      for U. parvum was 7.1; for U. urealyticum--11.2. CONCLUSION: Ratios between
      indexes obtained during quantitative study of pure genital micoplasma cultures by
      using 2 methods were established.

PMID- 25051694
TI  - [Study of sensitivity of microflora isolated from biosubstrates of surgical
      profile patients to bacteriophage].
AB  - AIM: Study sensitivity of nosocomial microbes--causative agents of post-operative
      infectious complications in surgical profile patients to bacteriophages.
      MATERIALS AND METHODS: Microbe isolates from biosubstrates of 223 surgical
      patients served as material. Microbes were isolated from blood, urine, wounds,
      intravascular catheters, abdominal cavity drainage, discharge of pharynx, trachea
      (343 strains). Phagolysability of strains was determined by Ott method. RESULTS:
      A good lysability of Pseudomonas aeruginosa, Klebsiella, Escherichia coli by
      specific complex and monophages and lower--of staphylococci and enterococci was
      found in the presence of 83% methicillin-resistant staphylococci strains and 94%
      Gram-negative bacteria strains producing extended spectrum beta-lactamases.
      CONCLUSION: Continuation of use of various bacteriophage preparations against
      Gram-negative bacteria and implementation of measures to adopt phage preparations
      to staphylococci and enterococci are perspective considering multiple resistance
      of microbes to antibiotics.

PMID- 25051695
TI  - [Algorithm of toxigenic genetically altered Vibrio cholerae El Tor biovar strain
      identification].
AB  - AIM: Development of an algorithm of genetically altered Vibrio cholerae biovar El
      Tor strai identification that ensures determination of serogroup, serovar and
      biovar of the studied isolate based on pheno- and genotypic properties, detection
      of genetically altered cholera El Tor causative agents, their differentiation by
      epidemic potential as well as evaluation of variability of key pathogenicity
      genes. MATERIALS AND METHODS: Complex analysis of 28 natural V. cholerae strains
      was carried out by using traditional microbiological methods, PCR and fragmentary
      sequencing. RESULTS: An algorithm of toxigenic genetically altered V. cholerae
      biovar El Tor strain identification was developed that includes 4 stages:
      determination of serogroup, serovar and biovar based on phenotypic properties,
      confirmation of serogroup and biovar based on molecular-genetic properties
      determination of strains as genetically altered, differentiation of genetically
      altered strains by their epidemic potential and detection of ctxB and tcpA key
      pathogenicity gene polymorphism. The algorithm is based on the use of traditional
      microbiological methods, PCR and sequencing of gene fragments. CONCLUSION: The
      use of the developed algorithm will increase the effectiveness of detection of
      genetically altered variants of the cholera El Tor causative agent, their
      differentiation by epidemic potential and will ensure establishment of
      polymorphism of genes that code key pathogenicity factors for determination of
      origins of the strains and possible routes of introduction of the infection.

PMID- 25051696
TI  - [VNTR-genotyping of Vibrio cholerae strains isolated from objects in the
      territory of Russian Federation in 2012].
AB  - AIM: VNTR-typing of Vibrio cholerae strains isolated in the territory of Russian
      Federation in 2012. MATERIALS AND METHODS: 71 Vibrio cholerae O3 and 3 V cholerae
      O1/O139 strains were used in the study. Genotyping was performed by using PCR for
      5 VNTR-loci. RESULTS: Multilocus VNTR-typing allowed to group the strains into 31
      VNTR-genotypes. Genotypes were divided among 10 discrete clusters by results of a
      cluster analysis. The presence of tcpA gene is clearly linked with the presence
      of VcB locus. Each geographic region was characterized by their own VNTR
      genotypes. CONCLUSION: In the course of the carried out VNTR-genotyping of V.
      cholerae isolated in 2012, 2 types of vibrio population formation were detected.
      A geographic attachment to specific regions was characteristic for most of the
      genotypes.

PMID- 25051697
TI  - [Group enterovirus infection due to coxsackievirus A16 in Northwestern Russia].
AB  - AIM: Study features of epidemic process and etiology of oral cavity and limb
      enterovirus exanthema group diseases in a number of territories of Northwestern
      Russia. MATERIALS AND METHODS: Isolation and identification of non-poliomyelitis
      enteroviruses from material of patients was carried out according to WHO
      recommendations. Phenotyping and phylogenetic analysis of enteroviruses was
      carried out. RESULTS: In 3 territories of Northwestern Russia oral cavity and
      limb enterovirus group diseases were registered. Children aged less than 14
      years, predominately aged less than 3 years, were shown to be involved in the
      epidemic process. Coxsackie A16 enteroviruses from 27 samples of patients were
      isolated in cell cultures and identified by using specific sera. Coxsackie A16
      enteroviruses from 16 samples were identified by using partial sequencing of VP1
      genome area. Phylogenetic analysis has shown that the identified Coxsackie A16
      viruses distributed among 2 phylogenetic groups. CONCLUSION: Coxsackie A16
      enteroviruses that had never been detected in the region previously were
      established to be the etiologic factor of oral cavity and limb enterovirus
      exanthema group disease in the 3 territories of Northwestern Russia. The data
      obtained give evidence on the necessity of epidemiologic and virological control
      for enterovirus infection with the aim of obtaining novel information on the
      circulation of non-poliomyelitis enteroviruses in the population and the
      establishment of development patterns for epidemic process of this infection.

PMID- 25051698
TI  - [Use of GIS technologies in development of a cadaster of stationary unfavorable
      by anthrax points in Krasnodar region].
AB  - AIM: Development of a cadaster of stationary unfavorable by anthrax points in
      Krasnodar region by using GIS technologies. MATERIALS AND METHODS: Ageographical
      information system (GIS) of ESRI program--Arc GIS 10.1 was used for the
      composition of an electronic cadaster of stationary unfavorable by anthrax
      points. Topographic basis--electronic maps of Krasnodar region (M 1:200 000).
      RESULTS: An evaluation of safety by anthrax of Krasnodar region areas bythe
      amount of stationary unfavorable by anthrax points situated in its territories,
      by their activity during the 76 year observation period was given. Spatial
      adjoint analysis of ecological timing of stationary unfavorable by anthrax points
      to soil and landscape zones in Krasnodar region was carried out. CONCLUSION:
      Electronic cadaster of stationary unfavorable by anthrax points in Krasnodar
      region may serve as a basis for purposeful implementation of prophylaxis
      measures.

PMID- 25051699
TI  - [Epidemic variants of norovirus genotype GII.4 in Nizhny Novgorod in 2006 -
      2012].
AB  - AIM: Genotyping of noroviruses that had circulated in the territory of Nizhny
      Novgorod during 6 epidemic seasons (2006 - 2012), detection of dominating
      genovariants and analysis of their change. MATERIALS AND METHODS: Feces samples
      from children hospitalized in an intestinal infection department of one of the
      infectious disease hospitals of Nizhny Novgorod served as material for the study.
      Noroviruses were detected by reverse transcription polymerase chain reaction.
      Genotypes and gene variants were determined by analysis of nucleotide sequences
      of viral genome regions coding capsid protein and RNA-dependent RNA-polymerase.
      RESULTS: During examination of 6589 children with an acute intestinal infection
      between July 2006 and June 2012 noroviruses were detected in 17.55% of cases.
      Nucleotide sequences of capsid and/or polymerase gene regions were determined for
      114 norovirus isolates. Genotyping has shown that noroviruses of 8 various
      genotypes had circulated in the territory of Nizhny Novgorod--GII.1, GII.2,
      GII.3, GII.4, GII.6, GII.7, GII. 12, GII.13 with the domination of GII.4
      noroviruses for the whole observation period. A dynamic of change of epidemic
      variants of genotype GII.4 noroviruses that had been accompanied by an increase
      of frequency of detection of norovirus in children hospitalized with acute
      intestinal infection similar to global was established. A short-term circulation
      of GII.4 2006b-NN 2008 norovirus subvariant in spring of 2008 and spread of
      genotype GII.12 norovirus during 2009, 2010 epidemic season were also shown.
      CONCLUSION: The data obtained give evidence to the necessity of norovirus
      circulation monitoring with the aim of early detection of novel virus variants
      that may determine an increase of norovirus infection morbidity.

PMID- 25051700
TI  - [Mechanisms of formation of post-vaccinal immune response in children immunized
      with APDT and ADT-M preparations].
AB  - AIM: Study the mechanisms of formation of cell and humoral immunity against
      pertussis, diphtheria and tetanus in children immunized with immunobiological
      preparations (APDT vaccine and ADT anatoxin). MATERIALS AND METHODS: 30
      practically healthy children (6 - 9 years of age) immunized with APDT and ADT-M
      preparations had TLR2, TLR4 expression determined in mononuclear cells (MNC).
      Vaccine preparations (APDT, ADT-M, AD-M, AT) and Corynebacterium diphtheriae
      gravis tox+, C. diphtheriae mitis tox- and Bordetella pertussis 345 were used as
      ligands. Cytokine production was determined in EIA. Content of anti-diphtheria,
      anti-tetanus and anti-pertussis antibodies--by PHA reaction and EIA. RESULTS:
      During stimulation with vaccines and B. pertussis 345 strain MNC were
      characterized by an increase (p < 0.05) of expression level of TLR2 and TLR4 and
      did not respond to stimulation with C. diphtheriae gravis tox+ and C. diphtheriae
      mitis tox- strains. Similar results were obtained during study of cytokine
      production (TNFalpha, IL-1, IL-6). A direct correlation between levels of
      antitoxic antibodies against diphtheria and tetanus (R = 0.486), antibacterial
      antibodies against pertussis and diphtheria was detected (R = 0.529). CONCLUSION:
      Analysis of cytokine production profile and determination of surface TLR
      expression can be used during evaluation of functional status of innate immunity
      cells and intensity of post-vaccinal immunity.

PMID- 25051701
TI  - [Evaluation of some immunological indexes in children with allergic diseases and
      obesity].
AB  - AIM: Study some immunological indexes in children with allergic diseases
      depending on bodyweight and clinical manifestations of allergy. MATERIALS AND
      METHODS: A correlation analysis of relationship of indexes of natural resistance
      (phagocytosis, complement), immunoglobulin level and main lymphocyte populations
      with body weight in 214 children aged 12 - 17 years with various allergic
      diseases (rhinitis/ rhinoconjunctivitis, atopic dermatitis, bronchial asthma) was
      carried out. The children were divided into groups based on body mass index
      (BMI): 73 (34%) children with normal weight, 74 (35%) overweight and 67 (31%)
      obese. RESULTS: The analysis has shown that the frequency of detection of
      children with obesity is the highest for age 12 - 14 years. With the increase of
      age the number of obese children decreases (OR - 9.0; 95% CI: 1.56 - 51.87; p =
      0.008 and OR - 0.27; 95% CI: 0.08 - 0.94; p = 0.04, respectively). An
      interrelation of BMI with clinical exacerbations of allergy was detected. Out of
      166 patients with allergic diseases combined with bronchial asthma excessive
      weight was detected in 62 (37%), obesit--in 57 (34%) and normal weigh--in 47
      (28%). In a group of 48 children with allergy without asthma excessive weight was
      noted in 12 (25%), obesit--in 10 (21%) and normal weigh--in 26 (54%) of patients.
      In children with bronchial asthma excessive weight occurs almost 3 times more
      frequently than in children with allergy and without asthma. Differences could
      not be detected in 3 groups of children when immune status indexes were compared,
      except total IgE and NK cell levels. Total IgE level was the highest in obese
      children (2.7 log), differed significantly from the level in obese (2.46 log) and
      normal weight (2.37 log, r = 0.32, p < 0.05) children. The relative content of NK
      cells in blood of obese children was significantly higher than in children
      withnoormal and excessive weight (r = 0.41). The analysis of significant
      correlation coefficient indexes detected correlative associations of some
      immunological indexes with BMI. In overweight children a negative relation
      between the level of complement and BMI (r = -0.61) and positive relation with
      phagocytosis index (r = 0.58) were detected. CONCLUSION: Obesity in children with
      allergic diseases is associated with an increase of conjugation of immunological
      indexes manifesting in an increase of number of natural killers (NK),
      phagocytosis indexes, increased total IgE level against the background of
      negative interrelation with the main populations of lymphocytes, that in general
      influences aggravation of allergopathology in the form of a higher frequency of
      detection of atopic bronchial asthma.

PMID- 25051702
TI  - [Effect of ribosomal proteins of respiratory bacteria on adhesive properties of
      buccal epitheliocytes].
AB  - AIM: Study the effect of ribosomal proteins of respiratory bacteria composing the
      basis of the immune-modulating preparation ribomunil on adhesive properties of
      buccal epithelium of healthy donors, and carry out comparison of this parameter
      during use of other bacterial products. MATERIALS AND METHODS: Various amounts of
      bacterial ribosomal proteins, Escherichia coli (serotype O127:B8) and one-day
      Staphylococcus aureus (strain 5983) culture supernatant were added to "buccal
      epitheliocytes--candida" system and incubated. Buccal cells were washed after the
      incubation from non-bound candida and differentiated microscopically by the
      amount of cells with various levels of candida adhesion. Separate effect of
      ribosomal proteins on buccal cells and candida was studied, as well as their
      impact on the production of secretory products of buccal cells. RESULTS: Buccal
      epitheliocytes in control adhered on average 14.6 candidiasis cells. After
      incubation with bacterial ribosomal proteins the index decreased by 2.3 +/- 0.2
      times. During separate addition of ribomunil to buccal cells and candida,
      ribosomal bacterial proteins were shown to have effect only on epitheliocytes.
      Activity of ribosomal proteins had a selective character, as shown by the lack of
      effect under the influence of S. aureus supernatant on buccal cells as well as an
      increase of adhesion under the influence of lipopolysaccharide on epitheliocytes.
      Viability of cells in all the cases remained at a level of 90 - 98%. Buccal cells
      during contact with ribomunil produced a complex of soluble mediators that took
      part in its blocking effect. CONCLUSION: The increase of stability of mucosal
      tract to microbial adhesion is an element of innate immunity and may be one of
      the components of immune-protecting effect of bacterial ribosomal proteins.

PMID- 25051703
TI  - [Pathogenetic features of infection caused by hepatitis C virus in individuals
      from groups with high risk of parenteral infection by this virus].
AB  - AIM: Study features of pathogenetic characteristic changes of infection caused by
      hepatitis C virus (HCV) in individuals that belong to different groups with high
      risk of parenteral infection (GHRPI). MATERIALS AND METHODS: 3219 blood sera
      obtained from individuals of 5 various GHRPI and 1541 unpaid blood donors were
      studied for the presence of anti-HCV. Anti-HCV-positive sera were studied by
      using polymerase chain reaction to detect HCV RNA in qualitative and quantitative
      variants. RESULTS: By using molecular-genetic methods the presence of HCV RNA and
      its concentration in HCV antibody-containing blood sera obtained from individuals
      of 5 various GHRPI and a group of unpaid donors infected early by HCVwas
      determined. Distinctive features that characterize the process of HCV infection
      natural evolution in individuals from various GHRPI were established to be lower
      frequency of spontaneous virus elimination and higher frequency of acute
      infection chronization, as well as a relatively higher viral load. CONCLUSION:
      The regularities detected indicate a higher level of epidemiologic danger for
      individuals from GHRPI.

PMID- 25051704
TI  - [Species and quantitative characteristics of pharyngeal mucosa microflora in
      pregnant women].
AB  - AIM: Species and quantitative characteristics of upper respiratory tract (URT)
      mucosa microflora in women at gestation period. MATERIALS AND METHODS: The
      results of a bacteriological study of 68 samples of mucus from posterior
      pharyngeal wall in women at gestation period (from 14 weeks), 52 of those--from
      pregnant women with acute respiratory infection (ARI) symptoms and 16--from women
      without signs of disease, are presented. Qualitative and quantitative composition
      of microflora was studied by a generally accepted bacteriological method.
      RESULTS: During primary bacteriological study 111 microorganism cultures were
      isolated. 88 (79.3%) of strains belonged to Gram-positive flora, 20 (18.0%)--to
      Gram-negative, and Candida genus fungi constituted 3 (2.7%) isolates.
      Streptococcus pyogenes and Moraxella catarrhalis were isolated from pregnant
      women with ARI signs at 23.1% and 5.8% frequency of occurrence, respectively. A
      higher detectability of Staphylococcus aureus--in 31.3% and Candida spp.--in 6.3%
      of women who did not complain as opposed to patients with URT lesions (in 21.2
      and 3.9%, respectively) was determined. In patients without ARI signs the amount
      of bacteria did not exceed 10(5)--10(6) CFU/ml, in pregnant women with ARI
      diagnosis in 8 of 52 cases semination of pharyngeal mucuswas observed--10(7)-
      10(8) CFU/ml. CONCLUSION: Prevalence of S. aureus, Streptococcus agalactiae, S.
      pyogenes, Streptococcus mutans in composition of pharyngeal mucus microflora of
      pregnant women both with URT lesion signs and without them was shown, however the
      degree of semination by pathogens in the groups was different that determined the
      severity of disease manifestations.

PMID- 25051705
TI  - [Proteome mass-spectrometric analysis and typing of Vibrio cholerae strains
      isolated in the territory of Russian Federation in 2010 - 2012].
AB  - AIM: Conduction of a comparative proteomic mass-spectrometric (MS) analysis using
      a personal database of V. cholerae protein mass-spectra and genetic VNTR-typing
      of cholera causative agent strains. MATERIALS AND METHODS: V. cholerae O1 El Tor
      strains - 7, V. cholerae non O1/non O139 - 2. Protein profiling and VNTR
      genotyping of strains was carried out on MALDI TOF-MS Autoflex (Bruker Daltonics)
      mass-spectrometer and SIS Cholera-strains-VNTR. RESULTS: The established
      community of a proteomic profile of epidemic cholera vibrio strains isolated in
      2010 - 2012 in Moscow allowed to determine Indian origin of a toxigenic strain
      isolated in Taganrog in 2011. M/z proteins distinguishing V. cholerae O1 and non
      O1/non O139 strains were identified. Proteomic analysis confirms the results of
      VNTR-genotyping. CONCLUSION: Study and typing of V. cholerae members with
      determination of their origin and phylogenetic relationship is possible using a
      collection of V. cholerae mass-spectra.

PMID- 25051706
TI  - [Cell analogs of viral proteins].
AB  - Horizontal transfer of genes between viruses and their hosts played an important
      role in the evolution of various eukaryotes including contemporary mammals as
      well as the pathogens themselves. Elements of viruses of various types can be
      found in the genome of animals. Endogenous retroviral elements composing up to 8%
      of human genome length not only determine its high flexibility and rapid
      adaptation potential. Many of virus genes such as Fv1, Lv1, Lv2 being analogues
      of capsid and other proteins determine effective suppression of viral replication
      after cell penetration by the causative agent. Introduction of these elements
      into genome of a wide variety of animals from fish to primates could have taken
      place against the background of global natural cataclysms of viral origin.
      Integration of retrovirus genes coding surface glycoproteins with
      immunosuppressing domains into genetic apparatus of animals served as an impetus
      to the development of viviparity and spread ofplacental mammals. Their cell
      analogs syncytins perform a dual function: take direct part in the formation of
      syncytiotrophoblast layer of placenta and ensure tolerance of immune system of
      mother to embryo. The acquisition of cell genes by viruses also played an
      important role in their evolution: various interleukins and other modulators of
      immune response introduced into viral genome from cell genetic apparatus became
      one of the most important factors of pathogenicity of a wide variety of causative
      agents including poxviruses, cytomegalovirus, Epstein-Barr virus and many others.
      Evolutionary pathways of the virus and host are thus inseparable from each other,
      and character of one of these directions is largely dictated by the vector of
      another.

PMID- 25051707
TI  - [Protein toxins of Staphylococcus aureus].
AB  - Main scientific-research studies regarding protein bacterial toxins of the most
      widespread bacteria that belong to Staphylococcus spp. genus and in particular
      the most pathogenic species for humans--Staphylococcus aureus, are analyzed.
      Structural and biological properties of protein toxins that have received the
      name of staphylococcus pyrogenic toxins (PTSAg) are presented. Data regarding
      genetic regulation of secretion and synthesis of these toxins and 3 main
      regulatory genetic systems (agr--accessory gene regulator, xpr--extracellular
      protein regulator, sar--staphylococcal accessory regulator) that coordinate
      synthesis of the most important protein toxins and enzymes for virulence of S.
      aureus, are presented.

PMID- 25051708
TI  - [Investigation of Triazavirin antiviral activity against tick-borne encephalitis
      pathogen in cell culture].
AB  - The efficacy of Triazavirin against the tick-borne encephalitis virus was
      estimated in the sensitive cell culture vs. the active drug Ribavirin. In a
      concentration of 128 mcg/ml Triazavirin was shown active in inhibition of the
      tick-borne encephalitis virus reproduction (strain Sofiin) by accumulation in the
      SKEV cell culture.

PMID- 25051709
TI  - [Rapid determination of cephalexin in biological media].
AB  - The behavior of cephalexin in pharmaceutical and biological media was studied by
      spectrophotometric method. The ranges of linearity and the limits of cephalexin
      detection were determined. The possibilities of spectrophotometric cephalexin
      determination in mixed saliva and in blood serum were shown. Optimal conditions
      of proteins precipitation were revealed. Pharmacokinetic parameters of cephalexin
      in oral fluid of patients with sinusitis were determined.

PMID- 25051710
TI  - [Stimforte action on the main inflammation characteristics in experimental
      animals contaminated by Herpes simplex-1].
AB  - In the brain and lungs of the experimental animals contaminated by Herpes simplex
      1 there were detected much higher levels of the thiobarbituric acid-stained lipid
      oxidation products and proteolytic activity, evident of the inflammation process.
      Stimforte lowered the inflammation indices to the level, close to that in the
      brain of the noninfected animals. Yet the drug provided lower titers of the virus
      in the brain, lungs and serum in the contaminated animals and arrested the
      infection process by stimulation of the immune system. The mechanism of the
      inflammation suppression is discussed.

PMID- 25051712
TI  - [Treatment approaches for bronchopulmonary infection in myasthenia gravis
      patients].
AB  - Nineteen patients with bronchopulmonary infection and myasthenia gravis were
      enrolled in the study. The microbiological analysis of the specimens of phlegm
      and bronchial secretion revealed both grampositive and gramnegative bacteria. All
      the isolates were susceptible to the antibiotic used (cefoperazone/sulbactam).
      Intravenous immunoglobulins (IvIgs) were used to increase the treatment efficacy,
      to opsonize the infection foci and to decrease the hospitalization terms. The
      antibiotic therapy and simultaneous use of intravenous immunoglobulins provided
      higher clinical efficacy in 16 out of 19 patients (84.2%).

PMID- 25051711
TI  - [Oflomelid ointment: activity against hospital microbial strains].
AB  - Ofloxacin susceptibility was tested with the use of 100 hospital isolates by the
      disk diffusion method vs. the activity of Oflomelid ointment tested by the cavity
      method. It was shown that the hospital isolates of all the species were
      susceptible to the Oflomelid ointment, while susceptibility to ofloxacin was
      preserved in S. epidermidis, the susceptibility of Acinetobacter spp., E. coli,
      Proteus spp. being intermediate. Such a difference in the susceptibility of the
      isolates was evidently due to the properties of polyethylene glycols in the
      ointment composition.

PMID- 25051713
TI  - [Efficiency of antibiotics in children with acute respiratory infection
      complicated by pneumonia dependent on the acetylation type in the Far North
      regions].
AB  - Clinical characteristics of some diseases are defined by the phenotype of
      metabolic reactions, for example N-acetylation. Genetic polymorphism due to the
      activity of N-acetyltransferase (N-AT) is common in the majority of human
      populations. Consequently, persons with "slow" or "fast" acetylation phenotype
      should be identified. N-AT catalyzes acetylation of a number of medical products.
      Efficiency of pharmacotherapy is mostly associated with the specific features of
      medical products biotransformation. The processes of biotransformation with
      participation of acetyltransferase, monooxygenase or other ferment systems are
      under the gene control. The aim of the study was to characterize the features of
      the clinical course of acute respiratory infection complicated by pneumonia as
      dependent on the acetylation phenotype to predict the character of the disease
      and optimize the used antibiotic therapy among the native population (Yakut) and
      the arrived (Russian) in the Far North Regions (Sakha, Yakutia). 112 children
      with acute respiratory infections complicated by pneumonia and 49 practically
      healthy ones were examined. For the children with low N-AT activity (less than
      30%) it was recommended to be treated with gentamicin which directly takes part
      in the acetylation and provides the antibiotic therapy efficiency in 80% of the
      cases. The use of cephalosporin antibiotics (beta-lactams), the metabolism of
      which is not directly connected with acetylation reactions provided the
      efficiency in 20% of the cases.

PMID- 25051714
TI  - [Value of probiotic in reducing frequency of infectious complications in
      premature infants].
AB  - Fifty five premature infants with very low body weight were observed as
      inpatients to assess effectiveness of the nursing. The standard program of the
      care included: adequate primary resuscitation, respiratory support (use of
      surfactant), thermal mode, early provision of nutrients with full or partial
      parenteral nutrition, antimicrobial therapy and if possible early enteral
      nutrition. The patients of the main group (n = 29) along with the standard
      therapy (the volume of the enteral nutrition of 5 ml or more) were treated orally
      with liquid probiotic based on E. faecium L3 in a dose of 0.5 ml (5 x 10(8) CFU)
      3 times a day for 14 days. The control group (n = 26) was under the standard
      therapy. The effectiveness of the infants management was estimated by the
      frequency of disruption of the nutrition, the frequency of infectious
      complications, the changes in the hematologic indices, the dynamics of the
      composition of the intestinal microflora. The infectious complications were
      evident from perinatal viral infection, intraamniotic infection, necrotizing
      enterocolitis. In the main group patients there was recorded a significant
      decrease of the frequency of infectious complications: 20.7% against 53.9% in the
      control group patients. The use of probiotic strain E. faecium L3 in the preterm
      infants promoted conservation of the immunomodulatory function of the intestinal
      indigenic microflora and restricted the growth of the nosocomial flora.

PMID- 25051715
TI  - [Action of antibiotics as signalling molecules].
AB  - It was thought that antibiotics should be produced by soil microorganisms to
      inhibit the growth of competitors in natural habitats. Yet it has been shown that
      antibiotics at subinhibitory concentrations may have a role as signalling
      molecules providing cell-to-cell communication in bacteria in the environment.
      Antibiotics modulate gene transcription and regulate gene expression in microbial
      populations. Subinhibitory concentrations of antibiotics may cause a number of
      phenotypic and genotypic changes in microorganisms. These transcription changes
      are dependent on the interaction of antibiotics with macromolecular receptors
      such as ribosome or RNA-polymerase. Antibiotic signalling and quorum-sensing
      system are important regulatory mechanisms in bacteria. It was demonstrated that
      antibiotics interfered with quorum-sensing system.

PMID- 25051716
TI  - [Mechanisms of nephrotoxic action of immunodepressants, calcineurine inhibitors].
AB  - The use of immunodepressants in the medical practice provided tens of thousands
      of favourable outcomes of the liver, kidney or heart transplantation and
      significant success in the treatment of a number of autoimmune diseases.
      Calcineurine inhibitors (cyclosporine A and tacrolimus) provoke a number of
      adverse reactions. Among them nephrotoxicity is clinically most dangerous.
      Complex estimation of the immunological and biochemical indices in the treatment
      with calcineurine inhibitors is an important precondition for increasing the
      efficacy of immunodepressive therapy and decreasing the frequency and level of
      the adverse reactions.

PMID- 25051717
TI  - [Association of the ABCB1 gene with risk for uveal melanoma].
AB  - The study investigated the association of the ABCB1 C3435T polymorphism gene with
      the risk for uveal melanoma (UM). Genotyping was carried out using the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. All
      the tumors under study were histologically verified. The patients with UM were
      found to have a high frequency of predisposing alleles and genotypes of this
      polymorphism in the patients with UM. The CC genotype of the ABCB1 C3435T
      polymorphism was shown to be associated with the increased risk of UM (OR = 8.5;
      p = 7.10(-6)). A significant correlation was first found between the frequency of
      the CC genotype of the ABCB1 C3435T polymorphism and the height of a tumor and
      degree of its pigmentation (p = 0.0391 and p = 0.0381, respectively, Fisher's
      test). A marginal association was first shown between the CC genotype of the
      ABCB1 C3435T polymorphism and the vascular state and histological type.

PMID- 25051718
TI  - [Specific features of gene amplification on the long arm of chromosome 17 in
      different molecular genetic subtypes of breast cancer].
AB  - The frequency of gene amplification and coamplification of HER2/neu, TOP2A and
      the centromeric region of chromosome 17 (CEP17) was examined in 265 breast cancer
      (BC) cases belonging to different molecular genetic subgroups. Luminal B breast
      cancer was found to be characterized by the increased probability of
      coamplifications (CEP17 and HER/neu, HER2/neu, and TOP2A) on chromosome 17. At
      the same time, the amplification of just three loci on one chromosome is a rare
      event and encountered in 17% of luminal B breast cancer cases (or 1.1% of all BC
      cases). That of HER2/neu in conjunction with elevated CEP17 count is
      statistically significantly more rarely accompanied by deletion of TOP2A rather
      than its amplification. The findings suggest that there are different
      amplification mechanisms in different BC molecular genetic subgroups.

PMID- 25051719
TI  - [Structural features of cardiomyocytes in the atrialized right ventricle in
      patients with Ebstein anomaly].
AB  - Intraoperative biopsy specimens were used to analyze the sizes and ultrastructure
      of cardiomyocytes (CMC) in the atrialized right ventricle (ARV) versus those in
      the right ventricle (RV) and right atrium (RA) in 32 patients aged 9 months to 57
      years with Ebstein anomaly. The mean CMC diameter in ARV, RV, and RA did not
      differ significantly in patients less than 10 years; that was equal in ARV and
      RV, but higher in RA in patients over 10 years of age. No specific atrial
      granules were found in the CMC of ARV, RV, and RA; but T system channels and
      multiple intercalated disks were encountered significantly more frequently than
      in the RA cells. Individual CMCs showed abnormal myofibrils with specific
      accumulations of Z-band material (more commonly in RA), as well as nuclear
      displacement under the sarcolemma (more commonly in ARV and RV). Conclusion. ARV
      cardiomyocytes preserve ventricular specificity in patients with Ebstein anomaly.

PMID- 25051720
TI  - [Impairments in the ultrastructure and macro- and microelement composition of
      hard tooth tissues in caries in patients with hypothyroidism and in those without
      thyroid disease].
AB  - Extracted teeth were studied in patients with hypothyroidism, by applying
      electron and atomic force microscopy. This method allows one to have extended
      morphometric characteristics. The patients with hypothyroidism were found to have
      superficial and internal changes in the enamel, dentin, and cement of intact and
      carious teeth. The macro- and microelement composition of teeth were
      investigated. In hypothyroidism, the resistance of dental tissue depends on the
      homogeneous structure of enamel and dentin.

PMID- 25051721
TI  - [Morphological changes of neurons and neuroglial cells in the brain of senescence
      accelerated prone 1 (SAMP1) mice].
AB  - Computerized morphometry was used to examine the sizes of neuronal bodies and the
      compactness of arrangement of neurons and neuroglial cells in layers III and V of
      the sensorimotor cortex in senescence-accelerated prone 1 (SAMP1) mice (an
      experimental group) and senescence-accelerated-resistant strain 1 (SAMR1) ones (a
      control group). In the SAMP1 mice as compared to the SAMR1 ones, the neuronal
      body sizes were significantly unchanged; the compactness of their arrangement
      decreased by 17 and 20% in layers III and V, respectively; that of neuroglial
      cells significantly increased by 14% in layer III only. In the SAMP1 mice versus
      the SAMR1 ones, the glial index rose by 36% in layer III and by 24% in layer V.
      During simulation of physiological aging, the sizes of neuronal bodies were shown
      to be virtually unchanged in the cerebral cortex; the compactness of their
      arrangement (cell counts) moderately reduced and that of neuroglial cells
      increased, which caused a rise in the glioneuronal index that was indicative of
      the enhanced supporting function of neuroglial cells during the physiological
      aging of brain structures.

PMID- 25051722
TI  - [The hepatotropic activity of runihol and ademethionine against experimental
      liver damage caused by first-line antituberculosis drugs].
AB  - Experiments on 62 male albino outbred rats investigated the impact of 14-day use
      of the oral hepatotropic agents ademethionine and runihol in different doses in
      liver damage caused by a antituberculosis combination (HRZ). HRZ-induced liver
      damage was shown to be accompanied by the development of cytolysis and
      cholestasis. The test drugs in the doses under study had a mixed effect, by
      reducing the magnitude of biochemical manifestations of these syndromes. Both
      drugs favored the recovery of the structure of the liver and the reduction of the
      extent of carbohydrate, protein, and fat dystrophies of the organ. As in previous
      investigations, ademethionine was found to have enhanced activity of alterative
      processes in the liver.

PMID- 25051723
TI  - [IgG4-related chronic periaortitis with retroperitoneal fibrosis].
AB  - The paper describes a case of IgG4-related chronic periaortitis in a 56-year-old
      man. Computed tomography revealed stenosis of the abdominal aorta and both common
      iliac arteries due to calcified atherosclerotic plaques, in this connection,
      bifurcation aorta-common femoral bypass surgery was performed. Intraoperatively,
      a solid retroperitoneal mass intimately connected with the walls of vessels was
      revealed in the retroperitoneal space around the aorta and iliac arteries.
      Histological examination ascertained rough fibrous connective tissue growth, a
      marked lymphoplasmacytic infiltration with an admixture of eosinophils, and
      formation of lymphoid follicles with germinal centers. Immunohistochemical
      examination revealed the plasma cell expression of CD20, IgG, IgG4, and kappa and
      lambda light chains in the inflammatory infiltrate. Because of active immune
      inflammation, further conservative therapy was recommended.

PMID- 25051724
TI  - [Generalized pneumocystosis in HIV infection].
AB  - The paper describes a rare case of rapidly progressive generalized pneumocystosis
      in HIV infection in a 43-year-old patient who died 4.5-5 months after disease
      onset. The specific feature of the case is that in pneumocystosis there was
      multiple organ dysfunction, as well as infiltrate decay to form small and large
      lung cavities similar to tuberculosis ones. Autopsy disclosed Pneumocystis
      induced changes in the liver, spleen, lymph nodes, and the wall of the ileum.
      Pneumocystosis and HIV infection were diagnosed only posthumously. The
      specificity of organ diseases was immunohistochemically verified.

PMID- 25051725
TI  - [Malignant peripheral nerve sheath tumor with perineural differentiation
      (malignant perineurinoma) of the cervix uteri].
AB  - The paper describes a case of a malignant peripheral nerve sheath tumor with
      perineural differentiation and at the rare site of the cervix uteri in a 57-year
      old patient. The diagnosis was established on the basis of extensive
      immunohistochemical examination, by excluding the similar neoplasms and detecting
      an immunophenotype characteristic of perineural differentiation. There are data
      available in the literature on the morphological and immunophenotypical
      characteristics of this tumor.

PMID- 25051726
TI  - [Iliac lipoleiomyoma with development of invagination and acute ileus].
AB  - Lipoleiomyoma is a benign tumor that consists of smooth muscle and fat
      components, which occurs in less than 0.5% of cases among all benign intestine
      tumors. The paper describes a case of acute ileum obstruction with the
      development of lipoleiomyoma invagination in a 23-year-old woman and presents the
      endoscopic verification and microscopic and immunohistochemical examination of
      the removed tumor.

PMID- 25051727
TI  - [Possibility of DNA isolation from archived autopsy tissues for molecular genetic
      studies].
AB  - Optimal conditions were defined for DNA isolation from formalin-fixed and
      paraffin-embedded (FFPE) archived autopsy lung tissue slices. The quality of DNA
      preparations isolated from the FFPE archived slices was assessed and their
      suitability for further molecular genetic analysis estimated. DNA isolated from
      the FFPE slices stored less and more than 10 years was suitable for molecular
      genetic studies in 100 and 66.7% of cases, respectively.

PMID- 25051728
TI  - [High-grade thyroid cancer].
AB  - The paper analyzes the data available in the literature on the morphological and
      prognostic features of relatively rare high-grade thyroid cancer. It shows the
      difficulties and unsolved problems of morphological diagnosis and the
      possibilities of current methods for immunohistochemical and molecular genetic
      studies to determine the malignant potential of the tumor and prognosis.

PMID- 25051729
TI  - [Impaired angiogenesis and lymphangiogenesis in diabetes mellitus].
AB  - The review summarizes the results of the latest studies dealing with the
      mechanisms of impaired angio- and lymphangiogenesis in diabetes mellitus and the
      role of these disorders in the development of the disease and its vascular
      events.

PMID- 25051730
TI  - [New approaches to the classification, grading, and prognosis of renal cell
      carcinoma].
AB  - Renal cell carcinoma is a heterogeneous group of tumors. Frequent revisions of
      its histological classification and TNM staging system complicate the
      retrospective studies of large patient groups and hamper the estimation of
      survival rates and quality of life for patients. Due to improving therapeutic
      possibilities, the problems of the staging, morphological diagnosis, grading, and
      determination of prognostic factors of renal cell carcinomas have assumed a
      particular significance. Despite the long-term history of studies dealing with
      renal cell carcinoma, there is no general agreement among specialists at to these
      issues. The paper reviews the recent International Society of Urological
      Pathology Consensus held in Vancouver in March 2013.

PMID- 25051731
TI  - [100 years of drinking water regulation. Retrospective review, current situation
      and prospects].
AB  - There is considered the history of the development of legislative requirements to
      the regulation of the quality of drinking water in different countries and
      international organizations during the period from 1912 to the present time. In
      terms of comparative analysis there is analyzed the current state of regulatory
      frameworks of the Russian Federation, WHO, EU, Finland, the UK, Singapore,
      Australia, Japan, China, Nigeria, the United States and Canada in the field of
      providing favorable conditions of population drinking water use. There has been
      noted the significant progress in standardization of the content of the biogenic
      elements and chemical pollution of drinking water in the absence of uniform
      requirements to the composition and properties of drinking water globally, that
      is bound to the need to take into account the national peculiarities of drinking
      water supply within the separate countries. As promising directions for improving
      regulation of drinking water quality there are noted: the development of new
      standards for prioritized water pollution, periodic review ofstandards after
      appearance of the new scientific data on the biological action of substances, the
      use of the concept of risk, the harmonization of the normative values and the
      assessment of the possibility of introduction into the practice the one more
      criterion of profitableness of population water use--the bioenergetic state of
      the water.

PMID- 25051732
TI  - [Migration of industrial radionuclides in soils and benthal deposits at the
      coastal margins of the temporary waste storage facility (TWSF) of the Northwest
      Center for Radioactive Waste Management (SevRAO) and its influence on the
      possible contamination of the sea offshore waters].
AB  - For obtaining the integral information about the current radiation situation in
      the sea offshore waters of the temporary waste storage facility (TWSF) of the
      Northwest Center for Radioactive Waste Management "SevRAO" in the Andreeva Bay
      and in the settle Gremikha with a purpose of a comprehensive assessment of its
      condition there was performed radiation-ecological monitoring of the adjacent sea
      offshore waters of the TWSF. It was shown that in the territory of industrial
      sites of the TWSF as a result of industrial activity there are localized areas of
      pollution by man-made radionuclides. As a result of leaching of radionuclides by
      tidal stream, snowmelt and rainwater radioactive contamination extends beyond the
      territory of the sanitary protection zone and to the coastal sea offshore waters.
      To confirm the coastal pollution of the sea offshore waters the levels of
      mobility of 90Sr and 137Cs in environmental chains and bond strength of them with
      the soil and benthal deposits were clarified by determining with the method of
      detection of the forms of the presence of radionuclides in these media. There was
      established a high mobility of 137Cs and 90Sr in soils and benthal deposits
      (desorption coefficient (Kd) of 137Cs and 90Sr (in soils - 0.56 and 0.98), in the
      sediments - 0.82). The migration of radionuclides in environmental chains can
      lead to the contamination of the environment, including the sea offshore waters.

PMID- 25051733
TI  - [Characteristics of regulatory system in children exposed to the environmental
      chemical factors].
AB  - In children residing in areas with a high content of a number of aromatic
      hydrocarbons in ambient air and organochlorine compounds in drinking water there
      were studied the blood levels of these compounds, as well as the assessment of
      the indices of the immune and neuroendocrine systems was performed. The higher
      blood content of phenol and formaldehyde has been established and there was
      identified an array of organochlorine and aromatic compounds not detected in the
      control group children. In the blood of the children of a study group there was
      found an imbalance of indices of cellular components of innate and adaptive
      immunity, pro- and anti-inflammatory cytokines, as well as increased
      concentrations of free thyroxine and serotonin in the blood serum, which
      indicates to a change in the functions of regulatory systems in children exposed
      to organochlorine and aromatic compounds.

PMID- 25051734
TI  - [Heavy metals as a factor of possible environmentally caused illnesses in the
      Astrakhan region].
AB  - There are presented data about heavy metals as pollutants of the environment and
      the factors of environment-related diseases. There is given the brief information
      about the appearance of heavy metals in the environmental objects and the
      possible occurrence of diseases caused by trace elements deficiency in the
      region. There are discussed difficulties of the clinical and laboratory
      diagnosis, associated with general symptoms of many diseases and lack in the
      medical facilities the equipment for objective detection of heavy metals in human
      biosubstrates.

PMID- 25051735
TI  - [Immunological methods for assessing health in exposure to ambient air
      pollution].
AB  - In the article there have been analyzed the materials obtained in the study of
      human health state on the results of the study of immunological status. It was
      shown that the In mass hygienic studies the detection of the state of the human
      immune system has been shown to be the one of the most promising methods for the
      determination of human health state, as the immune system is the most vulnerable
      and feels the changes in the environment. At the same time it was pointed out
      that the non-invasive method for determining the human immunity is the most
      accessible.

PMID- 25051736
TI  - [Clinical and hygienic substantiation of individual biocorrection for
      ecologically dependent conditions in the critical groups of the population of
      Ukrainian industrial areas].
AB  - In the article there is considered the problem of pollution of the environment
      and human body with heavy metals, the effectiveness of individual biocorrection
      in critical groups of the population--pregnant women and children residing in
      technologically contaminated areas. In spite of the correspondence of the content
      of abiotic heavy metals to their MACs in the environment, the concentration of
      lead and cadmium in the internal environment of the organism in 1,6-15,4 times
      was found to exceed physiological norms that accompanied by a significant
      deficiency of essential trace elements. Similar situation has been proved to lead
      to a reduction in mental health and ability to learn in children, as well as to
      the various complications in pregnancy. The obtained results served as the
      scientific substantiation of the feasibility of biocorrection of the trace
      element imbalance ecological dependent states in the population of the industrial
      region. The proved high clinical effectiveness of this hygienic biocorrection is
      a scientific justification for widespread introduction of pectin preparations for
      health promotion, prevention of ecologically dependent states and increasing the
      adaptive capacity of the organism.

PMID- 25051737
TI  - [Calculation of prognoses of lung cancer in males from technogenic contamination
      of atmosphere in the Kemerovo region].
AB  - In this paper there are described the variants of the models of the regression
      analysis (linear exponential, exponential and hyperbolic) for the detection of
      relationships between the lung cancer rate in the male population and
      anthropogenic emissions in the Kemerovo region. After analyzing of the each model
      there was chosen the one seemed to be the most adequate to describe the
      dependence of cancer incidence from pollutant emissions into the atmosphere. At a
      later stage this model has served for the calculation of the medium-term
      forecasting of lung cancer rate in males in the dependence on the actual number
      of man-made emissions in previous years.

PMID- 25051738
TI  - [The application of the multidimensional statistical methods in the evaluation of
      the influence of atmospheric pollution on the population's health].
AB  - The search and measurement of causal relationships between exposure to air
      pollution and health state of the population is based on the system analysis and
      risk assessment to improve the quality of research. With this purpose there is
      applied the modern statistical analysis with the use of criteria of independence,
      principal component analysis and discriminate function analysis. As a result of
      analysis out of all atmospheric pollutants there were separated four main
      components: for diseases of the circulatory system main principal component is
      implied with concentrations of suspended solids, nitrogen dioxide, carbon
      monoxide, hydrogen fluoride, for the respiratory diseases the main c principal
      component is closely associated with suspended solids, sulfur dioxide and
      nitrogen dioxide, charcoal black. The discriminant function was shown to be used
      as a measure of the level of air pollution.

PMID- 25051739
TI  - [Hygienic assessment of the radiation risk of radon emanation in the Altai Krai].
AB  - The unique climatic and geographical location of the Altai Krai determines the
      specific radiation dose load for the population, which is composed of the complex
      of radiological indices, the structure of which is largely dependent on the type
      of locality and, to a greater extent due to the action of radon, which is
      currently the main source of internal radiation of the population of upland
      districts and adjacent territories. There was performed a hygienic assessment of
      the radiation risk and the expected decline in life expectancy and population
      health due to radon exposure in the model areas of the Altai Krai. To calculate
      the additional risk there were used some models for radiation risk extrapolation:
      a risk constant model, model GSF (Jacobi's model), Lubin model (TSE/AGE/WL) and
      BEIR VI model for smoking and nonsmoking population, as well as the combined
      model. The lowest values of the radiation risk and the expected decline in life
      expectancy are typical for Charyshsko-Ust-Kalmanskaya zone, the maximum--for
      Kuryinsko--Pospelikhinskaya zone.

PMID- 25051740
TI  - [Hygienic aspects of the working conditions assessment and state of health of the
      workers of the railway departmental security forces].
AB  - There were performed a comprehensive hygienic evaluation of the working
      conditions of employment and analysis of morbidity with temporary disability
      (MTD) of the workers of the railway departmental security forces. There was
      proved a significant influence of accumulated period of work on MTD. The
      professional causality as of the respiratory diseases in shooters and dog
      handlers, as of diseases of the circulatory system in the administrative and
      managerial workers has been established.

PMID- 25051741
TI  - [Elemental status of the medical personnel of the emergency medical services in
      the city of Khanty-Mansiysk].
AB  - Spectrometric analysis of hair from 110 medical workers (54--from the Emergency
      medical services and 56--from polyclinics) was performed with the use of atomic
      emission spectrometry and mass spectrometry, inductively coupled argon plasma
      spectrometry (AES-ISP) methods. There were revealed features of the elemental
      status of the medical personnel of the Emergency medical services: a deficiency
      of Mg, K and Li was typical for this group (presented more then in half of
      cases).

PMID- 25051742
TI  - [Development of recommendations for legislation's harmonization of Eurasec member
      states in the field of children's healthcare rights in educational institutions
      of various types].
AB  - In the paper there are presented the main results of the performed study on
      comparative legal analysis of national legislative acts in the field of providing
      of children's rights for health care in institutions of various types for the
      delivery of recommendations for harmonization of legislation of States--members
      of the Eurasian Economic Community.

PMID- 25051743
TI  - [Hygienic aspects of cellular communication in school age].
AB  - In the article there are presented the materials of research on the spread and
      usage of mobile phones among children and adolescents of different age groups in
      the Russian regions, the data of the performed tests of cellular communication
      devices, as well as the established effects of electromagnetic radiation (EMR) on
      biological objects. Risk groups of schoolchildren for adverse effect of EMR on
      health have been determined.

PMID- 25051744
TI  - [Modern approaches to the primary prevention of the development of psychoactive
      substance dependence on the base of accounting of environmental and genetic risk
      factors].
AB  - In the work there was performed an assessment of the interaction of microsocial
      and genetic factors of the development of psychoactive substance (PS) dependence.
      The objects of the psycho-hygienic and molecular-genetic studies were 538 male
      patients from the specialized diagnostic and treatment center at the age from 17
      to 65 years with a diagnosis of "PS dependence" according to F10-F09 in the ICD
      10. There were determined personality predictors of early (before 25 years)
      manifestation of systematic abuse, such as low self-control, individualisticity,
      authoritarianism, unjustified optimism and reduced capacity for social
      adaptation. Manifestation of the PS dependence at an early age (25 years) is
      determined by the contribution of genotype 9R+ DAT gene in the combination with
      other predisposing genotypes A1 + DRD2/ANKK1, SS SERT and 7R+ DRD. The risk of
      development of PS dependence at a more younger age increases with the
      superimposition of individual predisposing genotypes ranging from 1,2 (7R+ gene
      DRD4) to 1,9 (A1 + gene DRD2/ANKK10 on a destructive milieu. Pairwise
      combinations of genotypes 7R+ DRD4 x A1+ DRD2, 7R+ DRD4 x 9R+ DAT, 9R+ DAT x A1+
      DRD2, 9R+ DAT x SS SERT significantly increase the risk by 2 or more times (2.5
      2.8). There was suggested an algorithm for the prenosological forecast of the
      development of PS dependence in adolescents and young men.

PMID- 25051745
TI  - [Ecologically-dependent vitamin-minerals insufficiency in the sportsmen's
      organism].
AB  - The authors revealed the reduction of saturation of iron, copper, zinc, E and B2
      vitamins in sportsmen's organism under high physical exercise. The negative
      effect was associated with the duration of training - competition cycles. The
      reduced vitamin-mineral saturation of the organism was associated with the low
      ferritin level and an imbalance in the hormonal regulation of erythropoiesis. The
      state of erythropoiesis can be a criterion performance of athletes, whereas a
      degree of saturation of the body with minerals and vitamins can be the criterion
      for prenosological diagnosis of their health and professional relevance.

PMID- 25051746
TI  - [The regional factors determining the formation of childhood disability in the
      Altai Krai].
AB  - Disability is one of the main indices of public health of the population.
      Disability rates indices for children can be applied in the study of public
      health of population and for determination of the influence of the array of the
      health-promoting factors. As a result of the performed studies it is possible to
      consider some regional regularities for the formation of childhood disability and
      the role of a number of factors in its formation.

PMID- 25051747
TI  - [Genotoxicity evaluation of nanoparticles].
AB  - There are considered the results of studies of genotoxicity of nanoparticles with
      an emphasis on studies in vivo. Oxidative stress was determined as a general
      mechanism genotoxicity of nanoparticles defined. There are reported the practical
      considerations relating to the genotoxic assessment of nanoparticles. In
      particular there was pointed out the priority of research in vivo, there was
      indicated to a possible dependence of the manifestation of effects as well on the
      properties of nanoparticles, as the timing of exposure, dose, route of
      administration, the peculiarities of the sample preparation. There was noted the
      desirability of the usage of positive controls in experiments. As tasks requiring
      solutions, there were separated the assessment of the ability of nanoparticles to
      the induction of gene mutations and evaluation of their genotoxic effects in
      embryonic and germ cells. There was given a conclusion on the general state of
      the problem and there were identified the priorities of research in
      genotoxicology of nanoparticles.

PMID- 25051748
TI  - [Biological testing of water with different structural states in rats and frogs].
AB  - The effect of water samples with different structural states on some
      physiological indices of white laboratory rats, 5 groups of 10 animals (5 females
      and 5 males) and frogs has been studied. The investigation was performed for 1
      month. For the determination of the content of liquid crystal associates (LCA) in
      water samples there was used the dilatometric method, the performance of
      experimental animals was studied by the swimming test (up to total fatigue). The
      performed experiment on growing rats with the use of water with varying degrees
      of structuredness showed that according to the weight gain there were optimal
      water "Lekor" and tap water, treated with Bioptron (the content of the structured
      fraction is 5.06 +/- 0.09% and 6.9 +/- 0.23%, respectively). On physical
      performance the best indices were in animals consumed water treated with the
      Bioptron lamp. In performance of experiments on frogs it was found that cardiac
      function in animals under experimental conditions over time weakens
      spontaneously: heart rate and cardiac output decline. Therefore, the effect of
      different water samples on the cardiac function was assessed on the intensity of
      its decrease for 15 minutes. In the experimental study of the effect of water
      with different content of LCA on heart rate and cardiac output of the frog it was
      found that the optimum level of structuredness of water is within the range of
      5.06 +/- 0.09% (in water "Lekor") - 6.9 +/- 0.23% (tap water treated with
      Bioptron). All the other water samples, the content of nanocrystals in which was
      below or above this range, has a pronounced inhibitory effect on the heart
      performance of the frog.

PMID- 25051749
TI  - [The effect of treatment of chrysotile with chloride iron (III) on the effect of
      genomic instability in cultured human lymphocytes].
AB  - All forms of asbestos are carcinogenic to humans, that caused the prohibition of
      its use in Europe, America, etc. However, the unique physical and chemical
      properties of asbestos and many opportunities for its applications in various
      industries and human activities require the creation of new technologies to.
      Analysis of genomic instability in human lymphocytes in a large range of doses
      (micronucleus test with cytochalasin B showed a decline of core indicators of
      genome instability (frequency of dividing cells with cytogenetic damage,
      asymmetry in the distribution of the genetic material in mitosis, proliferative
      activity) incubation of cells with asbestos modified chloride iron, as compared
      to the initial sample. These data are consistent with the results of analysis of
      the intensity of neutrophil chemiluminescence of luminol by exposure of human
      blood samples studied. Based on the findings made some practical recommendations
      to the protocol cytogenetic analysis of genomic instability of people exposed to
      asbestos.

PMID- 25051750
TI  - [Headspace analysis of volatile organic compounds (VOC) in drinking water by the
      method of gas chromatography].
AB  - In the paper there is presented a methodology of analysis of headspace 52
      volatile organic compounds in drinking water by the method of gas chromatography
      with the use of the chromatograph "Crystal 5000.2" with three detectors and
      automatic attachment Lab Hut 200N NT-200 for the preparation of the sample water
      and vapor phase input. The lower limit of detection for all compounds in the 2-10
      times lower than that of the corresponding standard value.

PMID- 25051751
TI  - [Chrysotile-asbestos induces cytogenetic effects in the rat's mesothelium in
      vitro and in vivo].
AB  - Under cultivation of rat peritoneal mesothelial cells in vitro in them there are
      appeared signs of the genomic instability, evidencing their transformation:
      increasing of the number of both binucleated cells with micronuclei and
      polynuclear cells and the increase of sizes and polymorphism. Asbestos greatly
      accelerates this process. Asbestos-induced carcinogenesis in vivo is accompanied
      in pleural mesothelium in the rats there also revealed with similar signs of
      genomic instability and cellular transformation.

PMID- 25051752
TI  - [Methodical approaches to evaluation of air pollution by emissions of motor
      vehicles in population areas].
AB  - There are results of comparative analysis of air pollution by emissions of motor
      vehicles in the residential districts of Ryazan via different methodical
      approaches. Emissions were calculated regarding analysis of the traffic intensity
      on the elements of the city traffic network. Relative emissions, equivalent
      relative emissions and relative coefficient of emission hazard were calculated
      for each district. Rating of the comparing districts was done according to the
      pollution level using the above-mentioned indices. Gorodskaya Roscha was detected
      as the most polluted district. The most informative approach was comparison of
      the residential districts according to the equivalent relative emissions and
      relative coefficient of emission hazard.

PMID- 25051753
TI  - [International legal framework of elderly rights protection].
AB  - Aging of the population is one of the dominant trends in the XXI century. It is
      expected that by 2050, more than a quarter of the world's population (27%) will
      be 65 years or older. Increase of older persons' proportion in the population of
      most countries entails a change in the scale and structure of morbidity requiring
      higher costs for medical care, social security, including pensions. Ageing
      appears on the international agenda for more than 30 years. The Human Rights
      treaty bodies rank the elderly as a vulnerable group, who are more susceptible to
      various forms of discrimination. However, there is currently no any international
      legal instrument specifically dedicated to the problems of protection of the
      elderly at a time when their discrimination and stigmatization is a very common
      phenomenon.

PMID- 25051754
TI  - [The personality of the doctor as a corner stone in the temple of gerontology].
AB  - The fundamentals of gerontology are not fundamental science and not dialectical
      materialism, but, in our opinion, particularly respect for elders. The very same
      attitude toward the elderly in the society has changed to the best party not so
      long ago, when the material ability had appeared to adequately support the
      elderly and implement the monotheistic values, such as the value to God of every
      life. Thanks to the presence in St. Petersburg at 1889 year well-organized places
      for medical care of oldster professor S. P. Botkin was able to implement the
      world's first large-scale complex research of old age, surveyed more than two
      thousand old people. Today's liberal model of providing education without
      upbringing is fraught with the most terrible consequences. We must not forget a
      number of artifacts in medicine, when the doctor in different civilizations
      ignored the Hippocratic Oath. These are Josef Mengele and Karl Brandt, the
      physicians of "Unit 731", Leiba Shatunovskii, the doctors of the clinic
      "Medicus", and many others. These facts force to carefully scrutinize the current
      time. So in the British newspapers the information appear about the dead from
      hunger and thirst old people in expensive nursing homes. It seems necessary to go
      back to the moral roots of medicine. The pride of the Russian medicine is a life
      physician Eugene S. Botkin, who ascended to Calvary with his crowned patient,
      Emperor Nicholas II, because he could not change his word of honor. Thus, in the
      Russian tradition, glorious Hippocratic writings oath strengthened by noble
      honor. Knight code of the Russian nobleman, described us as "4D" (in Russian):
      duty, virtue, goodness and leisure, is the best formula for education and self
      improvement noble doctor. Thus, it is proposed to pay attention to the unity of
      education and upbringing in preparing the next generation of doctors, which
      should strengthen the guarantees of the preservation of high moral relations to
      the old people and gains of fundamental gerontology.

PMID- 25051755
TI  - [The new methods in gerontology for life expectancy prediction of the indigenous
      population of Yugra].
AB  - The behavior of the state vector of human cardio-vascular system in different age
      groups according to methods of theory of chaos-self-organization and methods of
      classical statistics was investigated. Observations were made on the indigenous
      people of North of the Russian Federation. Using methods of the theory of chaos
      self-organization the differences in the parameters of quasi-attractors of the
      human state vector of cardio-vascular system of the people of Russian Federation
      North were shown. Comparison with the results obtained by classical statistics
      was made.

PMID- 25051756
TI  - [Forecasting of environmental health risk on the basis of the kinetic theory of
      aging of living systems].
AB  - The method of iterative congruence of search of parameters of kinetic
      mathematical model of aging of living systems according to medical statistics is
      developed. Its opportunities for the description of risk functions of mortality
      and life expectancy for the person and animals depending on environment factors
      are illustrated. The concept of forecasting of environmental risks--risks to
      population health from ecological factors of influence--is formulated.

PMID- 25051757
TI  - [Role of hormonal regulation and stress in the interaction of sleep and
      biorhythms in aging].
AB  - The present work describes bibliographic analysis of ontogenetic changes in
      hormonal regulation of sleep and circadian biorhythms. It is suggested that two
      stage, age-related dynamics of such changes may be related to differential
      occurrence registered by us earlier, of maxima of morbidity and mortality caused
      by a number of disorders, in middle-age and in senile period. It is proposed to
      concentrate future efforts on elaboration of mathematical models of ontogenetic
      regulation, on the basis of systems biomedicine.

PMID- 25051758
TI  - [Age changes of immunological, morphological and biochemical indices of male
      reproductive system].
AB  - The article analyzes the dependence of bactericidal activity of sperm--natural
      resistance factors controlling the survival of bacteria in the urogenital tract,
      on the age of men. These data are compared with the results of the standard (on
      the recommendations of the WHO) spermogram, reflecting reproductive health. Due
      to the fact that one of the main etiological agents of infectious disease groups
      in the male reproductive system in adulthood are Staphylococcus spp., we consider
      the level of bactericidal activity of sperm in resident and transient carriage of
      S. aureus and S. epidermidis.

PMID- 25051759
TI  - [Blood vessels in human dermis during aging].
AB  - A factor that potentially influences on skin aging is blood supply which
      determines global conditions for an organ or a tissue functioning, including
      skin. Scientific data on conditions of blood supply in the skin during aging are
      insufficient and contradictory. Therefore, this work was aimed to the study of
      age-related changes in the number of blood vessels in the human dermis. Blood
      vessels were visualized with immunohistochemical technique to two endothelial
      markers, as von Willebrand factor and antigen CD31. The results showed that von
      Willebrand factor and antigen CD31 are present in endothelial cells of blood
      vessels of dermis in all examined age periods, from 20 weeks of pregnancy to 85
      yeas. Intensity of immunohistochemical staining to von Willebrand factor is
      enhanced during age. Intensity of staining to CD31 is not changed with age. The
      number of blood vessels positively stained either to von Willebrand factor or to
      CD31 in dermis was decreased gradually with age. A total number of fibroblasts in
      dermis decreased with age. The number of PCNA+ fibroblasts in dermis showing
      their proliferative activity was decreased with the progression of age. The
      decrease in the number of blood vessels is statistically associated with that in
      the general number of fibroblasts and proliferating fibroblasts. Hence, a factor
      that leads to aged decrease in the number of dermal fibroblasts is diminished
      blood supply, and actions targeted to enhancement of blood supply are to be in
      the basis of clinical approaches to prophylaxis and treatment aging changes of
      the skin.

PMID- 25051760
TI  - [The peculiarities of calcium metabolism regulation in different periods of
      growth and development].
AB  - The review contains literature data about calcium metabolism regulation in
      different periods of growth and development. The analyses of retrospective and
      current sources of information about the regulation of calcium homeostasis under
      the theory of functional systems, the regulation of calcium metabolism in
      prenatal and postnatal periods of the development, the significance of calcium
      metabolism disturbances in the development of pathological conditions were
      showed.

PMID- 25051761
TI  - [Metabolic memory enhances hormesis effect to the copper ions in age-depended
      manner].
AB  - The ability of young and old rats to manifest the hormesis effect to lethal doses
      of copper sulphate and the ability to save the induced "adaptive" pattern of
      redistribution of copper ions after the transfer of animals in the standard
      conditions is the mechanism of metabolic memory. It was found that pretreatment
      of animals with low-dose (1 mg per 100 g body mass, i.e. 33% of the lethal dose)
      of copper sulfate induced the formation of their resistance to lethal doses (3 mg
      per 100 g), so the hormesis effect was manifested. Hormesis effect depended on
      the number of pre injections of small doses of copper sulphate in an S-shaped
      manner. The protective effect increased after 1 to 3 of preliminary injections of
      copper sulfate, and after four or more injections the hormesis effect decreased.
      It is shown that the cardinal role in intracellular pattern of copper ion
      redistribution play heat-stable copper binding proteins 12 kDa cytosolic
      proteins. The formed "adaptive" pattern of intracellular distribution of the
      copper ions may be reproduced, after at least, one month. The prolonged hormesis
      effect can be attributed to the forming metabolic memory. The intracellular
      distribution pattern of the copper ions was age-dependent. Age-related
      differences were found in hormesis effect induced by copper ions, which results
      in increased binding capacity of copper binding proteins in old animals, with a
      higher content of copper ions in the mitochondria and microsomes as compared to
      young animals.

PMID- 25051762
TI  - [Age dynamics of cell reaction in the preoptic hypothalamic nucleus during
      melatonin administration with a special reference to blockade and activation of
      the kisspeptinergic system].
AB  - Kisspeptin activates neurocytes and astrocytes of the preoptic hypothalamic
      nucleus of 1-, 3- and 24-month-old male rats. Kisspeptin antagonist (P-234)
      depresses the neurocytes, but not the astrocytes of the preoptic nucleus.
      Melatonin at a dose of 100 mkg/100 g b.w. inhibits the neurons of old male rats.
      During combined administration of melatonin and kisspeptin, as well as melatonin
      and P-234, the state of the kisspeptinergic system is crusial for the activity of
      the neurons in the preoptic nucleus of 1- and 3-month-old animals. However, in
      old rats melatonin significantly changes the neuron response of the preoptic
      nucleus to kisspeptin and its antagonist administration, while it's observed the
      neuron stimulation. Generally, the state of the kisspeptinergic system has a
      determining influence on the preoptic hypothalamic nucleus of the immature and
      young mature male rats. In old rats the cell functional state of the preoptic
      nucleus depends on the interaction of the kisspeptinergic system and melatonin
      level.

PMID- 25051763
TI  - [Expression of nitric oxide synthases in the retina of OXYS rats during
      retinopathy development].
AB  - Both the lack and excess generation of nitric oxide (NO) contributes to the
      pathogenesis of age-related diseases, according to the latest data including age
      related macular degeneration (AMD), which is a leading cause of vision loss in
      people over 65. The mechanisms of the effects of NO are not entirely clear, the
      information about changes in the expression synthase NO (NOSs) in the retina with
      age and the development of AMD are limited. We showed previously that the
      senescence-accelerated OXYS rats strain is an animal model of AMD. The purpose of
      the present research was to compare the transcriptional activity of genes NOSs:
      neuronal (nNOS), inducible (iNOS) and endothelial (eNOS) in the retina OXYS and
      Wistar rats (used as control) by real-time PCR. The study was carried out on
      animals at the age of 3 and 18 months during the period of manifestation and
      active progression of AMD-like retinopathy in OXYS rats. We showed that mRNA
      level of NOSs was not dependent on age in Wistar and OXYS rats. Interstrain
      differences in the level of eNOS mRNA were not detected, but the level of mRNA of
      nNOS in the retina of 18-month-old OXYS rats was 2,4 times higher than in age
      matched Wistar rats. Regardless of age the level of iNOS mRNA in OXYS rats was 7
      times lower than that in Wistar rats, but the protein content of iNOS in 3-month
      old OXYS rats (ELISA data) was increased. Perhaps such a paradoxical situation
      reflects a decreased reactivity of the immune system in the OXYS rats.

PMID- 25051764
TI  - [Regulation of content of cytokines in blood serum and of caspase-3 activity in
      brains of old rats in model of sharp hypoxic hypoxia with Cortexin and Pinealon].
AB  - While studying the effects of Cortexin and Pinealon (Glu-Asp-Arg) on the caspase
      3 activity in the brain, an interleykin-6 and a factor of tumor necrosis in blood
      serum of old rats under the sharp hypoxic hypoxia it was suggested that in
      hypoxia of brain conditions Pinealon forwards the increase of the neurogenesis
      and the decrease neuroinflammatory reactions to a reference level. With the sharp
      hypoxic hypoxia Cortexin reduces an ability of brain tissue of programmed cells
      death, but saves the content of interleykin-6 at high level.

PMID- 25051765
TI  - [Rat tissues antioxidant status correction by peptide delta sleep during
      physiological aging of the organism].
AB  - It is shown that exogenous delta-sleep inducing peptide increases glutathione
      antioxidant system level in rat tissues at different stages of ontogenesis, by
      subcutaneous injection to rats 2-24 months postnatal development in a dose of 100
      mg/kg animal body weight by courses of 5 consecutive days per month, and this
      effect is especially marked in non-renewable postmitotic tissues.

PMID- 25051766
TI  - [Epigenetic aspects of peptidergic regulation of vascular endothelial cell
      proliferation during aging].
AB  - Short peptides vesugen and D-7 have stimulated proliferation-associated protein
      Ki-67 decreased during aging in tissue-specific cell cultures received from young
      and old animals and in dissociated vascular endothelial cell cultures. Peptides
      vesugen and D-7 have interacted with promoter region of MKI67 gene coding protein
      Ki-67 that was obtained using methods of molecular docking. Both peptides have
      contacted with core promoter 5'-agcctcaaccatcaggaaaacaagagt-3' located in MKI67
      gene from -14 to +12 base pairs relative to the transcriptional initiation site
      through sequence CATC(ENSG00000148773). Thus, vasoprotective effect of peptide
      vesugen revealed previously in elder people could be realized through epigenetic
      regulation of Ki-67 gene expression.

PMID- 25051767
TI  - [Peculiarities of arterial access in endovascular surgery in elderly patients].
AB  - In elderly patients, when performing endovascular cathlabs manipulation the
      radial and cubital accesses is preferable. We propose a new arterial access on
      the back surface of the hand in the anatomical snuffbox. Artery catheterization
      of the hand in the anatomical snuffbox preserves intact the radial artery in the
      forearm for subsequent potential surgical interventions.

PMID- 25051768
TI  - [Factors significant for clinical-and-labor prognosis in elderly patients with
      ischemic heart disease after surgical myocardial revascularization].
AB  - Factors significant for clinical-and-labor prognosis in elderly patients with
      ischemic heart disease after surgical myocardial revascularization are
      considered. It is demonstrated that each level of the problem in consideration
      has its own significant factors. Besides, the most essential correlations between
      investigated factors are marked out. The results obtained would allow determining
      clinical-and-labor prognosis for patients with ischemic heart disease more
      correctly and develop the efficient programs aimed at their rehabilitation.

PMID- 25051769
TI  - [Complex estimation of the state of health, quality of life, level of
      psychological adaptation and rates of senescence of war veterans, suffering from
      arterial hypertension].
AB  - The article presents some aspects of the health status of the veterans of the
      Samara region. Intercommunication is marked between the level of social
      adaptation, quality of life and rate aging combatants. The study shows the effect
      of chronic posttraumatic stress disorder on the occurrence of psychosomatic
      pathology and development of senescence combat veterans suffering from arterial
      hypertension.

PMID- 25051770
TI  - [Significance age-related predictors of chronic heart failure in determining the
      risk of death in elderly patients with hypertension].
AB  - In order to establish the prognostic value of age-related pathogenesis and the
      development of heart failure related to lipid peroxidation, endogenous
      subclinical inflammation, apoptosis, sarcopenia, interstitial myocardial fibrosis
      in the risk of mortality and survival rates, for the first time the results of
      echocardiography, enzyme immunoassay, bioimpedansmetry with the scale of the
      Seattle model of heart failure performed in 84 elderly patients with arterial
      hypertension stage II (middle age 68,3 +/- 1,8 years) were compared. We found
      that the increased activity of markers of chronic heart failure progression was
      associated with an increased risk of death in patients. We identified the most
      important indicators in assessing the risk of death and prognosis of heart
      failure in elderly patients; their timely correction will imply an increase in
      life expectancy of older patients with chronic heart failure.

PMID- 25051771
TI  - [Age features of hemostatic system in people with insulin resistance and pre
      diabetes carbohydrate metabolism disorders].
AB  - In pre-diabetes disorders in which pathogenesis the insulin resistance (IR) plays
      a leading role, the risk of thrombosis due to increased coagulation factors,
      decreased concentration of physiological anticoagulants and inhibition of
      fibrinolysis is increased. Similar changes in the hemostatic system with aging
      are observed. We investigated the characteristics of the hemostatic system in
      middle-aged and elderly people with IR in the absence and presence of impaired
      glucose tolerance (IGT). It is shown that IR in middle-aged and elderly people is
      accompanied by increased content of plasminogen activator inhibitor type-1, which
      may lead to potential inhibition of fibrinolysis. An indication of significant
      prothrombotic changes associated with IR in the elderly are reduced a clotting
      time of blood plasma in the APTT test and elevated levels of soluble fibrin and D
      dimer. Intensity of these changes in the hemostatic system is enhanced in the
      presence of IGT. The results substantiate need for correction of hemostasis by
      reducing the IR.

PMID- 25051772
TI  - [Completion technology of pelvic surgery accompanying with cystectomy in elderly
      and senile patients].
AB  - Results of treatment of 204 elderly and senile patients who underwent
      cystprostatectomy or anterior pelvic exenteration are analyzed. A comparative
      analysis of two groups of patients whose operation ended with the traditional
      drainage through the anterior abdominal wall (n = 100), and bilateral perineal
      drainage (n = 104) is presented. Bilateral perineal drainage after operations on
      the pelvic organs, accompanied by cystectomy and extended lymphadenectomy in
      conjunction with the restoration of the peritoneum lateral pelvic walls, improves
      postoperative recovery of intestinal peristalsis, promotes an earlier reduction
      in the intensity of pain and morbidity in the early postoperative period.
      Perineal installation of drains is a simple in design and safe procedure. We
      recommend bilateral perineal drainage after operations on the pelvic organs,
      accompanied by cystectomy and extended lymphadenectomy.

PMID- 25051773
TI  - [Treatment of overactive bladder in older women increased doses of antimuscarinic
      drugs safe and effective alternative to existing methods].
AB  - The study included 95 female patients of 65 to 74 years (average age 67,1 years),
      who previously (more than 6 months before this study) took a course of
      monotherapy with hydrochloride trospium in higher dosages with unstable or weak
      effect. In this study, all patients were divided into three groups and were
      treated with two antimuscarinic drugs. The majority of older women suffering from
      OAB and treatment-resistant taking one antimuscarinic drug in high doses showed a
      significant positive progress in a state by adding a second antimuscarinic agent.
      The received side effects do not exceed thereof in comparison with treatment with
      a single drug.

PMID- 25051774
TI  - [The efficacy of peptide bioregulators of vessels in lower limbs chronic arterial
      insufficiency treatment in old and elderly people].
AB  - Atherosclerosis is a leading cause of obliterating diseases of the arteries in 80
      90% of cases. The main pathogenetic mechanism is endothelial dysfunction, leading
      to hypertension, diabetes, congestive heart failure. The desire of modern society
      to improve the quality of life increases interest of human health in general and
      sexual health in particular, because the erectile function is an important factor
      in the quality of life, which makes us look for more effective methods of
      diagnosis, treatment and rehabilitation. The objective of the study was to assess
      the effectiveness of vasoactive tripeptide Vezugen in patients with vasculogenic
      erectile dysfunction as manifestation of atherosclerosis. Treatment results of
      erectile dysfunction in 41 patients were studied. A comparative analysis of
      clinical and instrumental parameters of blood flow in the main penile arteries
      before and after monotherapy was undertaken. The results show that the blood flow
      through the main artery of the penis after Vezugen treatment significantly
      improved both clinical and by objective indicators.

PMID- 25051775
TI  - [To the question of frequency of mechanical eye trauma in senile patients in
      Azerbaijan].
AB  - The article presents the results of the trauma of the eyes for a period of 10
      years (2000-2009) in 601 hospitalized patients of 50 (min)-92 years (max) years
      old. By the age criteria, the eye injury most often occurred in senile patients
      (50.9%), the proportion of senile patients over time decreases due to the
      increase of middle-aged patients. By decades of age groups, there is a slight
      excess of the frequency injury index at the age of 51 to 60 compared with age
      from 61 to 70. As potential risk factors for injury the age-related changes in
      quality of vision cannot be excluded. Men were 438 (72.9%), women 163 (27.1%)
      with an average age of males 63.4 +/- 0.4 years, females--67.1 +/- 0.8. Timely
      provision of expert care, as a visual criterion, reflected the time factor of
      patients' addressing to the hospital. The analysis of the causes of eye injuries
      confirmed their diversity. The traumas received by the patients while falling
      (14.5 +/- 1.4) including--frequent due to the aggravation factor of the patient
      that determines both the injury and delayed treatment are noteworthy. According
      to addressing to the hospital, primary emergency aid was rendered on the first
      day only to 15.3 +/- 1.5% patients, within 1 to 3 days 34.9 +/- 1.9% were
      hospitalized, 4-7 days--10.5 +/- 1.2%, 8-14 days--7.5 +/- 1.1%. The problem of
      eye injury in senile patients remains topical, given the frequency of eye
      injuries in senile patients, given the high probability of somatic aggravation of
      the patients as a potential risk factor for injury, delayed treatment, which
      makes the problem of eye trauma in senile patients the one that demands increased
      and due attention.

PMID- 25051776
TI  - [Socio-demographic status of elderly and senile age people died from alcohol
      attributable states in Arkhangelsk].
AB  - To determine the characteristics of the socio-demographic status of elderly and
      senile age people died of alcohol-attributable states in Arkhangelsk, data from
      the medical certificate of death was analyzed. Data of death for persons who died
      in the city of Arkhangelsk in the period from 1 July 2011 to 30 June 2012 (one
      year) were copied out. The vast majority of alcohol conditioned deaths among men
      occurs in middle (working) age, 1/3 of women--over the age of 60 years. The
      alcohol-attributable mortality revealed the transformation of the structure of
      women over the age of 60 years compared with the mature age. Gender and age
      significantly affect the probability of death from alcohol only attribute states
      after 60 years. The results of the study indicate a different impact on the
      character of the individual sociodemographic factors on the probability of death
      from alcohol-attributable states in elderly and senile age.

PMID- 25051777
TI  - [The structure of psychopathology associated with addictive disorders, against
      alcohol addiction and the possibility of its neurometabolic correction of the
      elderly].
AB  - The article considers the actual problem in modern medicine, the study of
      psychiatric symptoms associated with addictive disorders on the background of
      alcohol abuse in the elderly. It is shown that neurotic pathology in elderly
      patients with alcohol dependence is characterized by the presence of six major
      symptoms, reflecting the excitation processes, overcoming compensation, deficit
      symptoms, irritation and stabilization of the pathological state. It is proved
      that Cytoflavin, maintaining a certain level of excitement in the cerebral
      cortex, provides the optimal voltage of compensatory mechanisms in older people
      in overcoming their psychiatric symptoms, connected with addictive disorders.

PMID- 25051778
TI  - [The influence of different types of physical exertions on the mature males'
      biological age].
AB  - We studied the biological age according to anthropometric indexes, mental,
      physical and both the types of working efficiency in 122 males at the age of 50
      59 years. All of them were devided into 5 groups: untrained individuals, going in
      for general physical training, sport veterans, specializing in endurance
      training, sport plays representatives, weight-lifters. We found out a younger
      biological age in sport veterans, who were carrying out dynamic exertions.

PMID- 25051779
TI  - [Capabilities of pharmacological correction with Reamberin the cerebrovascular
      disorders with ENT diseases of the elderly patients].
AB  - Endointoxication's syndrome and manifestations of immune deficiency observed
      among elderly patients with acute exacerbations of ENT diseases and concomitant
      cerebrovascular pathology. Reamberin in pathogenetic therapy arrests
      manifestations of intoxication and optimizes immunobiological homeostasis.

PMID- 25051780
TI  - [Theoretical aspects of the elderly people's adaptation to social reality
      conditions].
AB  - The article deals with various opinions of scientists concerning the "adaptation"
      concept and the need to determine clear criteria for diagnostics of the
      development level of social and psychological adaptation. At present, there is no
      reasonably sufficient desirable adaptation model at various life-cycle stages.
      The degree of satisfaction of the needs of the elderly people can be considered
      as an adjustment criterion.

PMID- 25051781
TI  - [II Russian symposium with international participation "light regime, aging and
      cancer"].

PMID- 25051782
TI  - [ Modern condition and prospects of development of cardiac surgery in the Armed
      Forces].
AB  - Authors consider the problem of delivery cardiac surgical care to contingent of
      the Defence Ministry. Perspective directions of development of cardiac surgery in
      the Armed Forces of the Russian Federation are the development of minimally
      invasive cardio surgery, endovascular development of modern methods of diagnosis
      and treatment, further development of electrophysiological methods for diagnosis
      and treatment of disorders of rhythm and conduction, the introduction of various
      kinds of auxiliary mechanical circulatory support systems in acute and chronic
      heart failure, development of transplantation in cardiac surgery, improvement of
      algorithm selection and referral of patients requiring cardiac care by providing
      primary health care to troop central military medical institutions, creating a
      single register of cardiac patients as part of the Armed Forces in order to
      determine the order and place of treatment, etc.

PMID- 25051783
TI  - [The concept "a case in outpatient treatment" in military policlinic activity].
AB  - Substantiates the necessity of transition of military policlinics to the
      accounting system and evaluation of their activity on the finished cases of
      outpatient treatment. Only automating data-statistical processes can solve this
      problem. On the basis of analysis of the literature data, requirements of the
      guidance documents and observational results concludes that preliminarily should
      be done revisal (formalisation) of existing concepts of medical statistics from
      the position of information environment which in use - electronic databases. In
      this aspect specified the main features of outpatient treatment case as a unit of
      medical-statistical record, and formulated its definition.

PMID- 25051784
TI  - [Membranes structure and physical and mechanical erythrocytes properties in the
      early period of traumatic brain injury caused by less-lethal firearms].
AB  - The dynamics of erythrocytes properties in the acute phase of traumatic brain
      injury caused by less-lethal firearms has been studied by the methods of atomic
      force and morphometry. The experiments have been performed on sheep by a Makarych
      pistol single shot at the parietooccipital area. It has been established that
      under the influence of the shock waves the erythrocyte disks and transmembrane
      liquid oscillatory fluctuations (flicker) are increased. The fluctuations are
      rapidly attenuated and the shock waves energy is accepted by cytoplasmic
      membranes lipoproteids. As a result the interface tlipid-protein, phase
      transitions are hastened. The membranes undergo heterogeneous structural,
      physical and mechanical transformations the character of which is determined by
      the phase transitions direction. In the spots of phospolipid liquid clusters
      accumulation the fluidity is increased and marks caused by membranes lamination
      and spreading appear. In the spots of phospholipids solid phase the surfaces
      become hydrophobic and marks caused by membranes local embrittlement and
      fragility appear. The transmembrane fluid hydrodynamic flows heterogeneity is
      increased due to deformation processes irregular spreading. The flows
      acceleration causes the hydrodynamic ruptures-like defects. The flows
      deceleration results in depressions evolving through the mechanism of creeping
      erosions.

PMID- 25051785
TI  - [About the treatment of battlefield injuries of the musculoskeletal system with
      the help of new "Rod field package"].
AB  - Injuries of the musculoskeletal system are at 60% of all battlefield injures and
      take first place in modern military conflicts. The main antishock measures are:
      pain management, emergency bleeding control, bone fragment positioning and
      fracture fixation. Specialist of the centre of traumatology and orthopaedics of
      the Burdenko General Military Clinical Hospital in cooperation with specialists
      of department of battlefield surgery of Mandryka Clinical Research and Training
      Medical Centre analysed the most effective domestic and foreign external fixators
      and developed Rod field package (RFP). The above mentioned researched had two
      stages. On the first (analytical) stage specialists formulated requirements for
      idea rod field external fixator. On the second (experimental) stage tests with
      the help of plastic models of long bones were carried out. The performed analysis
      showed, that installation of the external fixator is easy and fast, the external
      fixator is light and has capabilities for 3D bone fragment positioning and
      fracture fixation, the external fixator is radiotransparent. Implementation of
      this package into the clinical practice of delivery of battlefield emergency
      surgical care may improve results of treatment.

PMID- 25051786
TI  - [Focused ultrasound survey in surgery for abdominal trauma: methods and the
      capabilities in clinical use].
AB  - In severe abdominal trauma ultrasound provides fast and accurate diagnostics of
      damages and detect the source of internal bleeding. In the absence of trained
      professionals (in injury care centre of 2-3rd levels, In emergency situations) it
      is possible to use by the method of research in the reduced volume. The article
      presents a comparative analysis of the use of traditional methods and reduced
      ultrasound diagnostics of abdominal injuries on 56 victims. Concluded that
      reduced ultrasound is affordable, mobile, fast and accurate method of diagnosis,
      allowing to use it repeatedly.

PMID- 25051787
TI  - [Complex outpatient care to patients with osteoarthrosis and degenerative
      dystrophic diseases of juxtaarticular soft tissues].
AB  - The aim of the article is an evaluation of effectiveness of the complex
      outpatient care to patients with osteoarthrosis and degenerative-dystrophic
      diseases ofjuxtaarticular soft tissues. Recent researches showed that the key
      factors of the pathogenesis of diseases were degenerative-dystrophic and
      inflammatory changes in the synovio-entheseal complex ofparaarticular muscles'
      tendon. 411 patients with osteoarthrosis of 531 synovial joints and degenerative
      dystrophic diseases of periarticular soft tissues underwent sequential
      corticosteroid therapy combined with hyaluronic acid injections. In 84% of cases
      positive results were observed.

PMID- 25051788
TI  - [The use of percutaneous endoscopic gastrostomy for provision of the long-term
      enteral nutrition].
AB  - Percutaneous endoscopic gastrostomy for provision of the long-term enteral
      nutrition is well established in clinical practice because unlike from
      traditional gastrostomy and jejunostomy allowed to avoid many complications. The
      technique is used for enteral tube feeding in the absence of real positive
      predictive recovery of consciousness and swallowing function. During presented
      study from 387 patients with a gastrostomy imposed by percutaneous endoscopic
      technique, observed only 1,8% of suppurative complications and in 1% of cases -
      uncontrolled removal of the tube by the patient. Our experience allows us to
      recommend this technique for wide implementation in practice of medical
      institutions in case when it is necessity in enteral feeding more than 3 weeks of
      patients with impaired

PMID- 25051789
TI  - [Significance of the individual helio-climatic factors in hemorrhagic fever with
      renal syndrome morbidity formation of population in the district of military
      units dislocation].
AB  - Been outlined the experience of mathematics modelling of natural phenomena for
      determination of the impact of individual factors and their combination on the
      epidemic process development. Found that 97,9% of the variation of haemorrhagic
      fever with renal syndrome index of population in the study area determine six
      climatic factors: the Wolf number, rainfall in November, the highest level of the
      river during floods, the temperature of air in October, the maximum and minimum
      levels of snow cover in February. As the most significant factors, contributing
      to the spread of the disease under study, been determine the parameters of air
      temperature and the height of snow. In the troops proposed to use approved
      methodology of mathematics modelling to predict changes of epidemiological
      situation for the disease and for timely organization of preventive measures to
      avoid introduction of infection in military units.

PMID- 25051790
TI  - [Hypobaric chamber as a test of the aircrew of Russain Air Forces].
AB  - Authors research clinical medical importance of hypobaric ascends to an attitude
      of 5000 meters for 20 minutes for detection of latent forms of diseases and
      assessment of professional health and ascends to an attitude of 5000 and 6000
      meters for 5 minutes when performing psychophysiological training for high
      altitude flying. According to test of 1326 pilots of Russian Air Forces,
      including pilots with different diseases, hypobaric ascends showed high
      diagnostic effectiveness for the professional health assessment. By using of both
      methods it was revealed that frequency of detection of decreased tolerance to
      hypoxia is the same (in average in 2,7 and 3,1% of total number of patients). By
      ascends in 38 patients (2,9%) was revealed decreased tolerance to hypoxia of
      medium level. It indicated about low functional state and space capacity of
      pilots. It was proved that hypobaric ascends of 5000 and 6000 meters for 5
      minutes could be considered as an effective method of checkup of aircrew for the
      aviation physical examination.

PMID- 25051791
TI  - [Development of combat medical robots in the US Armed Forces].
AB  - The current article is dedicated to the problem of scientific research
      organization in the field of combat medical robots development in the US Armed
      Forces. The role of the Telemedicine and Advanced Technology Research Center is
      singled out. The project A Robotic System for Wounded Patient Extraction and
      Evacuation from Hostile Environments is described in more detail. It is noted the
      high cost of such technical systems development and operation.

PMID- 25051792
TI  - ["1st Therapeutic Red Cross Hospital" during the civil war].
AB  - The article presents the documentary information about the founding, the
      establishment and early years of the 1st Therapeutic Red Cross Hospital - in the
      future - Mandryka Central Military Clinical Hospital of the Ministry of Defence
      of the Russian Federation. Presented the work of the Hospital during the dificult
      period of the Civil War, typhus epidemic, famine and devastation. Specified its
      staffing structure, command, medical and administrative staff, travel and
      accommodation till the moment of the deployment in the Silver Lane in Moscow.

PMID- 25051793
TI  - [Reactions of the interneuronal synapses of rat brain to hypoxia during the early
      postnatal period].
AB  - The reactions of forming synapses in rat neocortex to the effect of hypoxia in
      the early postnatal period (day 2) were studied. Using immunocytochemistry for
      synaptophysin demonstratoion and electron microscopic methods, the sensorimotor
      cortex was studied in rats at days 3, 4 and 10 of postnatal development (6 to 10
      animals of each age) in both experimental and control groups (intact animals).
      Immunocytochemical study of the control animals demonstrated significant
      differences in the quantitative distribution of synaptophysin-positive structures
      in the different layers of the neocortex in the early postnatal period of
      development (day 5). It is shown that after exposure to perinatal hypoxia, more
      than 2-fold decrease of the optical density of the immunocytochemical reaction
      product took place together with the reduction of synaptophysin-positive granules
      distribution density in all cortical layers of. At the same time, electron-dense
      terminals demonstrating early degenerative processes were found. In the neuropil
      of the neocortex, a sharp decline in the number of growth cones, small processes
      and forming synapses was accompanied by significant changes of the electron
      density of synaptic, especially post-synaptic, membranes and densities. In the
      experimental animals, the number of growth cones and emerging synaptic structures
      were shown to increase only by postnatal day 10. Thus, the effects of hypoxia in
      the early postnatal period, causing disturbances of synaptogenesis, persist
      throughout the whole neonatal period examined.

PMID- 25051794
TI  - [Changes of y neuron formation in cat visual system during early postnatal
      ontogenesis under the influence of binocular rhythmic light stimulation].
AB  - To examine the effect of an artificial rhythmic light stimulation on the
      development of structural and functional organization of Y neurons of cat visual
      system in the ontogenesis, the distribution of the neurons immunopositive to SMI
      32 antibodies was studied in lateral geniculate nucleus (LGN) and posteromedial
      suprasylvian area (PMLS). Laminar distribution of SMI-32-positive neurons and
      neuronal body profile area were analyzed in intact animals (n = 4) and in kittens
      (n = 4) grown under conditions of rhythmic light stimulation with 15 Hz frequency
      for 4 months. In light-stimulated animals, changes in laminar distribution of
      immunopositive neurons were detected in both LGN (decline in the percentage of
      the immunopositive cells in C(M) layer) and in PMLS area (decrease in cell count
      in layer V). Morphometric analysis has shown the significant reduction of cell
      body profile area in immunopositive neurons in light-stimulated kittens only in
      layers III and V of PMLS area. The data obtained suggest that Y channel
      functional disturbances in light-stimulated animals are caused by the structural
      and metabolic changes detected in Y neurons.

PMID- 25051795
TI  - [Structural and quantitative characteristics of the amygdala and primary
      somatosensory cortex of alcohol-preferring and alcohol non-preferring rats].
AB  - The aim of the study was the structural and planimetric characteristics of the
      nuclei and intermediate formations of corticomedial and basolateral groups of
      structures of the amygdala and the primary somatosensory cortex in 10 alcohol
      preferring (AP) and 10 alcohol non-preferring (ANP) rats, as well as
      demonstration of the ifferences in concentration of dopamine and its metabolite-
      3,4 dihydroxyphenylacetic acid (DOPAK) in the amygdala. Measurements of absolute
      and specific areas of the structures studied were conducted on the
      cytoarchitectonic slides stained using Nissl cresyl violet method. No differences
      in the specific area of corticomedial and basolateral amygdala groups of
      structures were detected between two groups of rats studied. In ANP rats higher
      specific areas of the primary somatosensory cortex and of the amygdala in the
      left hemisphere were found, predetermined by the larger sizes of basolateral
      group. Analysis of DOPAK concentration in the amygdala revealed it in nearly
      equal quantities in AP and ANP rats, while, concentration of dopamine was
      significantly greater in AP rats. DOPAK/dopamine ratio was twice greater in AP
      rats which is indicative of dopamine accelerated metabolism.

PMID- 25051796
TI  - [Early reactive changes of the astrocytes in the midbrain paranigral nucleus
      after forebrain ischemia and cerebroprotector Ropren administration in rats].
AB  - The aim of this study was to detect morphological equivalents of
      cerebroprotective effect of polyprenol drug Ropren on the astrocytes of the
      midbrain paranigral nucleus (PNN) which are located outside the focus of
      forebrain ischemia in rats. In mature rats (n = 8) the cerebral ischemia was
      reproduced under the narcosis by bilateral occlusion of both carotid arteries.
      Four rats received daily intraperitoneal injections of 11.6 mg/kg of
      cerebroprotector Ropren. Sham-operated animals served as a control. The animals
      were decapitated at experimental day 7. Astrocytes of anterior ventral portion of
      midbrain PNN were studied using an immunocytochemical method demonstrating glial
      fibrillary acidic protein. The number of astrocytes, their cell body profile
      area, the length of their major processes and the distance between their cell
      bodies and capillary wall were measured. It was found that Ropren suppressed
      astrocyte hypertrophic reaction, their migration towards the vascular wall and
      presumably stimulated the proliferation of these cells.

PMID- 25051797
TI  - [Morphological characteristic of a motor unit afferent limb in hypokinesia].
AB  - Neuromuscular spindles (NMS) of soleus muscle and their vascular bed was studied
      in 250 mature male Wistar rats following long-term (30, 60, 120 and 240 days)
      hypokinesia. Material was studied using Kulchitsky, Mason and Ranson histological
      staining, electron microscopic and histochemical methods (demonstration of
      succinate dehydrogenase). It was found that initial changes involved the decrease
      of the lumen of precapillary arterioles (by 25.4%) and blood capillaries (by
      29.1%). These changes closely correlated with the increase of the subcapsular
      space width (by 34.7%), the decrease of NMS capsule thickness (by 48.7%) and
      equatorial zone diameter (by 17.9%). Activity of succinate dehydrogenase in the
      intrafusal muscle fibers was also decreased. As a result of disintegration of the
      majority of gamma-axon terminals, NMS cross sectional area was decreases by
      75.6%. Thus, during hypokinesia initial changes were detected in the sources of
      NMS blood supply, while their structural remodelling involved destructive
      alterations.

PMID- 25051798
TI  - [Structure and venous vascular bed of the rectum in Stavropol breed sheep].
AB  - This investigation was aimed at the study of macromorphology of the rectum,
      including its intramural and extraorgan venous vascular bed in 18-month-old sheep
      of Stavropol breed. The methods used included anatomical preparation,
      morphometry, contrast mass intravascular injection, separation of an intestinal
      wall into the individual layers and preparation of total samples. The thickness
      of rectal muscular coat in 18-month-old sheep was found to increase in the caudal
      direction which is interpreted as an adaptation of the intestine for the
      evacuation of condensed fecal masses through the anal canal lumen. Intramural
      rectal venous vascular bed included three plexuses: submucosal, muscular and
      subserosal. The prevalence of the veins of wide-field type with an index of 90
      120 in the rectal wall of a sheep results in the deceleration of the venous blood
      flow in the organ. At the same time, rectal intramural venous vascular bed
      possesses higher adaptive capacity in the cases of occlusion of the basic roots
      due to the well developed collateral network located between the roots of wide
      field veins. The major extraorgan venous vessel of sheep rectum is a cranial
      rectal vein. Presence of its terminoterminal anastomoses with caudal rectal and
      left colonic veins may provide a bypass rectal venous blood flow in the cases of
      a the obstruction of one of its major vessels of various etiology.

PMID- 25051799
TI  - [Pancreas structure in fetuses and newborn infants who died in the perinatal
      period].
AB  - In the pancreas of fetuses at weeks 22-40 of prenatal development (n = 111) and
      of newborn infants who died during the first week of postnatal life (n = 38) the
      changes were detected that were characterized by exocrine part hypoplasia,
      retardation of acinar pancreatocyte differentiation, connective tissue outgrowth,
      pancreatic (Langerhans) islet hyperplasia and hypertrophy. The results of the
      study have shown that with the increase of the total risk sum of the perinatal
      period pathology development (expressed in balls), the relative content of the
      insular part of the organ and the number of large pancreatic islets (larger than
      100 microm in diameter) decreased. The morphological features detected in this
      study indirectly reflect endo-ecologically discomfortable conditions of fetus
      development within the fetoplacental unit which increase the risk of
      polyendocrinopathy development and fetal intrauterine growth retardation. These
      polyendocrinopathies increase further the risk of endocrine disturbance occurence
      in childhood.

PMID- 25051800
TI  - [Variant anatomy of maxillar sinus according to the data of computer tomography
      with 3D function].
AB  - The paper presents the data on variant and individual anatomy of the maxillary
      sinus in 400 men and women of the I and II periods of adulthood obtained using by
      computer tomography with 3D function. It was found that in the I period of
      adulthood, 12.5% of individuals had the bony septa in the alveolar recess of the
      maxillary sinus which were oriented frontally--Underwood's septa. Individuals of
      the II period of adulthood had this septa in 20% of cases. Also in the second age
      group, 7.2% of the cases demonstrated the septa which are oriented sagittally.
      These structures were often associated with the bony canal of the infraorbital
      nerve. The detected variants of individual variability of the maxillary sinus
      have both theoretical and practical importance. In particular, during the
      planning of micromaxillotomy (through the endonasal access or fossa canina), the
      presence of bone septa, their location and the course of the infraorbital nerve
      canal should be taken into account.

PMID- 25051801
TI  - [Applied aspects of topographic-anatomical interrelations of female pelvic organs
      and cellular spaces].
AB  - The study of an autopsy material, obtained from females aged 15-74 years (145
      organ complexes), using the classical anatomical research methods, resulted in
      the topographic-anatomical substantiation of transvaginal surgical accesses to
      subperitoneal and peritoneal pelvic floors taking into account the variants of
      the uterus position. The projection-syntopic correlations of subperitoneal and
      peritoneal structures with vaginal fornix were examined, the latter was divided
      for this purpose into the limited areas--vaginal segments. It was found that the
      transvaginal accesses in the uterus position of the anteversio-anteflexio and
      retroversio-retroflexio (with more common symmetrical rela tions between the
      pelvic structures and vaginal fornix), should be performed in the projection of
      vaginal segments 10.5-1.5 and 5.5-6.5. Due to asymmetric projection-syntopic
      relations of subperitoneal and peritoneal pelvic structures with vaginal fornix,
      the optimal accesses are recommended in the projection of vaginal segments 12
      1.5, 11.5-2 and 6-6.5 in sinistroversio, sinistropositio with a clockwise uterine
      rotation, while in dextro-positio and counterclockwise uterine rotation, the
      accesses in the projection of vaginal segments 10.5-12, 10.5-1, 6-5.5 and 6-5 are
      preferable.

PMID- 25051802
TI  - [Peculiarities of tissue reactions to implantation of non-degradable surgical
      materials].
AB  - The method of light microscopy was used to study the reactions of the surrounding
      tissues to the implantation of non-degradable surgical materials (prolene 3/0
      thread made from polypropelene, the composite grid made from polypropelene or
      polyester with polylactic acid) in the subcutaneous adipose tissue of rats 1, 2,
      6 and 12 months after grafting. No less than 6 rats were examined in every time
      point. It was shown that the tissue reactions to implantation of different non
      degradable surgical materials follows the general pattern, characteristic of
      wound process and foreign body reaction. By the first month of observation in
      both groups of animals the stage of traumatic perifocal inflammation was replaced
      by the proliferative phase with the formation of new blood vessel and connective
      tissue. The tendency to reduction of the activity of productive inflammation was
      observed from the 1st to the 12th month together with the increased fibrous scar
      transformation of the granulation tissue.

PMID- 25051803
TI  - [Pulmonary neuroepithelial bodies in the rat].
AB  - This paper describes the study of the neuroepithelial bodies (NEB) in the lungs
      of adult healthy Wistar rats (n = 12). Using the immunocytochemical reaction
      demonstrating synaptophysin, NEB and immunopositive nerve terminals approaching
      them, were visualized. It was found that NEB were the structures constantly
      presented in the rat lung. In contrast to the diffuse neuroendocrine elements,
      NEB are characterized by grouped distribution of cells. It was found that some
      part of NEB had no efferent innervation.

PMID- 25051804
TI  - [Three-dimensional visualization of the brain ependyma and tanycytes].
AB  - The aim of this investigation was to develop an integrated approach to spatial
      reconstruction of the cells lining the ventricles of the brain using confocal
      laser microscopy and immunocytochemical reaction to vimentin. The work was
      performed on paraffin sections of rat brain of different thickness (5 and 10
      microm). To visualize the immunocytochemical reaction the fluorescent dyes in the
      visible range were selected: SYTOX Green selectively staining the nucleus and
      indocarbocyanin (Cy-3) conjugated with streptavidin. As a result of testing of
      various processing conditions, the protocol which allows to receive an intensive
      staining of the structures was developed. The set of fluorochromes proposed in
      confocal laser microscopy allows to separate easily the channels, to study the
      structures independently, if needed, and does not require the use of an expensive
      ultraviolet laser.

PMID- 25051805
TI  - [Paneth cells: history of discovery, structural and functional characteristics
      and the role in the maintenance of homeostasis in the small intestine].
AB  - Cells with acidophilic granules in the crypts of the small intestine were first
      described, along with the other cells of intestinal epithelium, in 1872 by a well
      known German anatomist, histologist and anthropologist G.A. Schwalbe, however
      they were named after an Austrian histologist and physiologist J. Paneth, who has
      performed their detailed morphological analysis in 1888. For many decades the
      role of Paneth cells (PCs) remained completely unclear, until in 1960-1970 the
      production of antimicrobial molecules by these cells was found. At present, it is
      established that PCs produce a broad spectrum of antimicrobial compounds, thus
      controlling the number and content of intestinal microbial populations. PCs are
      an important part of innate immunity defense mechanisms, however, by interacting
      with the other cells, they participate in the reactions of the adaptive immunity.
      By creating high concentrations of antimicrobial substances within the crypt, PCs
      protect intestinal stem cells from the damage by potentially pathogenic
      microorganisms, while by releasing some signaling molecules, they control the
      vital functions of these cells, being an important component of their niche.
      Affecting the host tissues and influencing the microbial populations, PCs play a
      significant role in the maintenance of homeostasis in the intestine.

PMID- 25051806
TI  - [Towards 150th jubilee of Kazan School of Neurohistology].

PMID- 25051807
TI  - [Theodor Kerckring (to the 375th anniversary of birth)].

PMID- 25051809
TI  - [World Cup preparation].

PMID- 25051808
TI  - [The conception of the human body structure in Ayurvedic treatises].

PMID- 25051810
TI  - [Daclizumab: Clinical trial of monoclonal antibody for the treatment of MS].

PMID- 25051811
TI  - [PHARMAGRIPS: structured pharmaceutical counseling in the self-medication of the
      common cold. A randomised controlled study (RCT)].
AB  - Many minor ailments are treated in Germany by self-medication. Most drugs
      dispensed by pharmacy staff are those for the common cold, general pain and
      gastrointestinal disorders. Whilst pharmacists express their need for further
      training in counseling on side effects, interactions and contraindications, they
      tend to receive feedback from patients to the effect that the drugs used have not
      worked. From July to October 2013 we carried out a prospective, single-blind,
      quasi-randomised controlled study on the effect of training on structured
      pharmaceutical advice in self-medication of the common cold (PHARMAGRIPS Study).
      Using a controlled, interventional study design we investigated whether it is
      possible to improve the pharmaceutical counseling in self-medication within a
      short time, by using an appropriate teaching method. The counseling should be
      made in a systematic way and refer to evidence-based content in order to avoid
      incorrect advice. We enrolled 86 pharmacists and assigned them randomly into the
      study protocol. Of those, 56 completed the study as planned and were analysed. In
      this study, we reviewed the structure of the average pharmaceutical consultation
      and added evidence-based content from the Cochrane Reviews on common cold. We
      then integrated this structured consultation in a methodical modem training
      program consisting of e-learning and live classes which we evaluated
      scientifically. For this purpose, we conducted telephone interviews with the
      participating pharmacists by using standardized case report forms. The case
      report forms contained the questions that the participants were supposed to ask.
      For every question asked, the participant received a certain amount of points, 18
      in total. The training was stated to be successful at the primary endpoint when
      an improvement of at least 3.5 out of 18 points was achieved on average. The
      secondary endpoints were related to various aspects of the interview process
      (medical history, limits of self-medication, evidence-based drug selection and
      integration of customer input in the consultation interaction). The training
      group improved in the primary endpoint by an average of 5.93 points (p < 0.001)
      and compared to the control group significantly in all secondary endpoints, with
      one participant managing to achieve the full score. The participants recognized
      the importance and practical relevance of the exercise in a short time and were
      able to implement even integrate complex content in their consultations and to
      give the customer appropriate advice.

PMID- 25051812
TI  - [Psychological aspects of diabetes].
AB  - The diagnosis of diabetes shakes up everyday life for the patients. Therefore,
      diabetes therapy also has to consider psychological aspects helping patients to
      cope with their disease. Additionally, the incidence of some mental health
      problems such as depression are associated with diabetes and may interact with
      diabetes therapy.

PMID- 25051813
TI  - [Are quinine-containing beverages dubious?].

PMID- 25051814
TI  - [Three medicine bottles with a special contents].

PMID- 25051815
TI  - [Vichy and the pharmacy].

PMID- 25051816
TI  - [Maaseik: the old private pharmacy renovated into her old glory].

PMID- 25051817
TI  - [The collection cabinet with miniature pharmacy in the Rijksmuseum in Amsterdam].

PMID- 25051818
TI  - [In memoriam pharmacist Leonard de Causmaecker].

PMID- 25051819
TI  - [Epidemic situation of oversea imported schistosomiasis in China and thinking
      about its prevention and control].
AB  - The imported schistosomiasis cases in the Chinese literature and reports from the
      infectious disease monitoring information system from 1979 to 2013 were collected
      and compiled. Totally 365 cases were reported to be infected with outside
      schistosomiasis, including 239 cases of schistosomiasis haematobia (74.0%) and 71
      cases of schistosomiasis mansoni (22.0%), and 42 foreigners (11.5%) and 323
      Chinese (88.5%). The infection areas involved 15 countries and regions in Africa.
      Totally 74.92% of patients worked in the construction or geological prospecting
      in the wild field. According to the analysis of these cases, we found that the
      management system of prevention and control of imported schistosomiasis cases was
      not perfect including the high missing re-port rate, high misdiagnosis rate, and
      no standard diagnostic criteria. We suggest that all the levels of CDC or health
      administrative authorities should adopt the following relevant control measures
      to strengthen the imported schistosomiasis prevention and control in order to
      reduce the damage to the public health and the risk of the spread of African
      schistosomiasis in China: (1) to establish and perfect the imported
      schistosomiasis monitoring and control system in China; (2) to integrate the
      dynamic information platform of labor export and establish the comprehensive
      prevention and control management system of infectious diseases; (3) to
      standardize the diagnosis and treatment of oversea imported schistosomiasis; (4)
      to strengthen the research on the transmission risk of imported schistosomiasis
      in the territory of China.

PMID- 25051820
TI  - [Studies on changes of vegetation and Oncomelania hupensis snails in Poyang Lake
      after impoundment of Three Gorges Project].
AB  - OBJECTIVE: To explore the impact and change regularity of Oncomelania hupensis
      snails and vegetation in the marshlands of Poyang Lake caused by the impoundment
      of the Three Gorges Project. METHODS: By using the methods of stratified
      systematic sampling and pinpoint navigation, the succession of vegetation was
      observed and the distribution of O. hupensis snails was investigated in a period
      of 8 years on 4 typical marshlands in Poyang Lake. The regularity of changes in
      vegetation and 0. hupensis snails was analyzed on the marshlands at high, medium
      and low elevations, respectively. RESULTS: After the impoundment of Three Gorges
      Project, the average flooding days of these 4 marshlands in 2004 and in 2008 were
      reduced of 74.8 and 65.8 days compared with those in 2002, the year just before
      the impoundment of the project, respectively. The change of spatial distribution
      pattern and the succession of dominant species of vegetation on the marshlands of
      Poyang Lake have taken place since 2005, and several vegetations showed a trend
      of moving toward the center of the lake. The hygrophilous vegetation has
      degenerated and gradually been replaced by mesophily meadow in the marshland area
      above 14 m elevation. Carex, Phalaris arundinacea and Polygonum appeared in large
      area and expanded slowly towards the center of the lake on the marshland below 14
      m elevation. O. hupensis snails were mostly found under the Carex association.
      The tendency of decreasing in density of snails and of migration of snail
      habitats towards low terrain was observed. CONCLUSIONS: The impoundment of Three
      Gorges Project has had a significant impact on hydrological regimes, and a new
      succession of vegetation has taken place in the marshlands of Poyang Lake. O.
      hupensis snails and the mesophily vegetation show a trend of migrating slowly to
      the areas of low elevation in the marshlands.

PMID- 25051821
TI  - [Contrastive analysis of environmental factors between Oncomelania hupensis snail
      marshland and snail natural death marshland in eastern Dongting Lake
      schistosomiasis endemic areas].
AB  - OBJECTIVE: To study the reasons of natural death of Oncomelania hupensis snails
      in marshland by comparing the differences of environmental factors between snail
      marshland and non-snail marshland in East Dongting Lake schistosomiasis endemic
      areas. METHODS: Two adjoining marshlands were selected, one was a snail marshland
      and another was a non-snail marshland. The measuring points were set by grid of
      "20 m x 20 m". The soil moisture, elevation, soil pH and temperature of the
      points were measured, and the snails of the points were surveyed. RESULTS: The
      elevation, soil pH and temperature of the snail natural death marshland were all
      lower than those of the snail marshland (P < 0.01). The soil moisture, elevation,
      soil pH and temperature of different snail densities in the snail marshland were
      different (P < 0.05). The soil moisture of the non-snail group was higher than
      that of other four groups (P < 0.01) and the soil moisture of the group with 0-11
      snails per frame was lower than that of other four groups (P < 0.01). The
      elevation of the group with 0-11 snails per frame was lower than that of the
      group with 24-39 snails per frame and the group with more than 39 snails per
      frame (P < 0.05). The soil pH of the group without snails was higher than that of
      other four groups (P < 0.01) and the soil temperature of the group with 0-11
      snails per frame was lower than that of the group with 24-39 snails per frame.
      The differences of soil moisture and elevation of different death snail densities
      were not significant, while the differences of soil pH and temperature were
      significant. The soil pH of the non-snail died group was higher than that of the
      2-died, 3-died and more than 3-died groups (P < 0.05). The soil temperature of
      the non-snail died group was higher than that of other four groups (P < 0.05).
      CONCLUSION: The elevation, soil pH and soil temperature within the range of the
      research may be the factors affecting the snail natural death and the soil
      moisture, elevation, soil pH and soil temperature may be the factors affecting
      the distribution of snails.

PMID- 25051822
TI  - [Relationship between Yangtze River floodplain micro ecological environment and
      distribution of Oncomelania hupensis snails].
AB  - OBJECTIVE: To explore the relationship between the Yangtze River floodplain
      ecological environment (vegetation, soil, water and light intensity) and the
      distribution of Oncomelania hupensis snails, so as to provide the evidence for
      ecological snail control. METHODS: Three regions (the Lu-Gang Bridge, Dragon Nest
      Lake in the bund, and Dragon Nest lake beach) were selected to investigate the
      plant characteristics (species, height, coverage, frequency and strain of
      clusters), soil characteristics (temperature, humidity, light intensity) and pH
      value. All the results were analyzed statistically with SPSS 18 software.
      RESULTS: A total of 920 boxes were investigated. The vegetation coverage was 3.7%
      63.5%, and the dominant population was Cyperusrotundus L. cluster on the
      marshland. The soil temperature was 19.0 degrees C-24.0 degrees C, pH 5.0-5.7,
      and humidity 53%-75%. There were statistical significants in average number of
      living snails and dead snails among 3 groups (P < 0.05). As the light intensity
      was strong in summer and weak in winter, the snails were in the back surface in
      summer and front surface in winter respectively. The average number of living
      snails was the most near the water. The difference was statistical significant (P
      < 0.01) among three ranges (0-1 m, 1-3 m and 3-5 m). CONCLUSION: The snail
      survival and distribution have close relations with micro ecological environment
      factors, such as vegetation, soil, water and light intensity.

PMID- 25051823
TI  - [Study on distribution and countermeasures of Oncomelania snails in beach
      wetlands of Runzhou section of lower reaches of Yangtze River].
AB  - OBJECTIVE: To understand the distribution of the river beach wetlands and
      Oncomelania snails in the lower reaches of the Yangtze River, and explore the
      countermeasures of snail control. METHODS: The river beach wetlands outside the
      Yangtze River levee were investigated and classified according to the
      hierarchical and classification system of wetlands of China. The snail survey was
      carried out in the beach wetlands of Runzhou section of lower reaches of the
      Yangtze River from 2004 to 2013. The change trend of snail areas and the
      densities was analyzed in the wetlands. RESULTS: The river beach of Runzhou
      section of lower reaches of the Yangtze River belongs to the riverine wetland.
      There was Oncomelania snail breeding except the permanent water area. At present,
      there were natural wetlands of 1303.0 hm2, human-made wetlands of 1479.0 hmb2 and
      wetland function changes of 1059.0 hm2 in the river beach of Runzhou section.
      There was the snail area of 181.4 hm2 in the natural wetland in 2013. The area of
      snail control by the molluscicide and environmental modification was 4624.55 hm2
      from 2004 to 2013. The decline rates of snail areas and densities were 66.53% and
      77.66% respectively. The existing Oncomelania snails were distributed in the
      natural wetlands. CONCLUSION: The human-made wetland is helpful to snail control.
      The snail control in the river beach wetlands should attach a great importance to
      the protection of wetland ecology.

PMID- 25051824
TI  - [Study on spatio-temporal pattern of mountainous Oncomelania hupensis snails at
      village scale in Eryuan County, Yunnan Province].
AB  - OBJECTIVE: To develop a spatio-temporal model of mountainous Oncomelania hupensis
      snails based on the Bayesian model, and to analyze and identify the spatio
      temporal pattern at a village scale. METHODS: The data including the intensity
      and spatial distribution of live and infected snails from 2000 to 2006 and the
      village boundary were collected. The independent and interactive spatio-temporal
      models were established, and then the best fitness model was selected to analyze
      the spatio-temporal pattern of live and infected snails. RESULTS: The interactive
      model of live snails and the independent model of infected snails were relative
      fitness models, and the models showed 95% CI (confidence interval) of the spatial
      and temporal coefficient included zero, and indicated that the spatial and
      temporal correlation of live and infected snails was not significant at a village
      scale. CONCLUSION: There is no significant spatial and temporal correlation of
      live and infected mountainous snails at a village scale, and the furthermore
      study should be carried out at a small scale.

PMID- 25051825
TI  - [GC/MS-based dynamic analysis of Eucalyptus camaldulensis extract on correlation
      of chromatography-activity against Oncomelania hupensis].
AB  - OBJECTIVE: To determine the contributions of main chemical compositions of
      extracts of Eucalyptus camaldulensis represented by GC/MS elute peaks to the
      molluscicidal activities, and explore a shortcut of looking for the effective
      components from natural products. METHODS: E. camaldulensis leaves were collected
      consecutively in 12 months at the same place, extracted with dichloromethane,
      analyzed by GC/MS, and their LC50(s) of molluscicidal activities were tested
      according to the method recommended by WHO. The correlation of the main
      components in 12 extracts and their molluscicidal activities were analyzed by the
      grey relative correlation analysis model with software GTMS 3.0. RESULT: All the
      dichloromethane extracts of eucalyptus leaves showed excellent molluscicidal
      activities with the highest LC50 of 0.257mg/L and 0.242mg/L for the samples in
      June and July and the lowest LC50 of 6.802 mg/L and 5.406 mg/L in December and
      January respectively. The structures of 16 main chemical components were
      elucidated by GC/MS and NIST Mass Spectral Library, most of which were
      monoterpenes and sesquiterpenoids. The gray correlation coefficients with
      activity were all over 0.5, the first five over 0.9 were 4,4, 8-Trimethyltricyclo
      [6.3.1.0 (1,5) ]dodecane-2,9-diol, (-)-Spathulenol, a structural isomer of (-)
      Spathulenol, Eucalyptol and Ledol. CONCLUSION: The most main ingredients in the
      dichloromethane extracts of E. camaldulensis leaves show good correlations with
      the molluscicidal activity, which suggests that the molluscicidal role is
      synergistically played by the multiple components together.

PMID- 25051826
TI  - [Analysis of epidemiological characteristics of advanced schistosomiasis in Hu
      nan province, 2012].
AB  - OBJECTIVE: To understand the epidemiological characteristics of patients with
      advanced schistosomiasis in Hunan Province, so as to provide the evidence for
      formulating the advanced schistosomiasis prevention strategies and measures.
      METHODS: The data of advanced schistosomiasis patients were collected and
      analyzed retrospectively with the cross section research method and description
      method in Hunan Province, 2012. RESULTS: There were 5 722 advanced
      schistosomiasis patients in Hunan Province, and among them, 4 112 patients were
      male (71.86%), and 1610 were female (28.14%). Totally 5311 patients came from the
      schistosomiasis endemic areas (92.82%) and 411 patients from non-schistosomiasis
      endemic areas (7.18%). The prevalence rate of advanced schistosomiasis was
      8.46/10,000. The mean age of advanced schistosomiasis patients was 60.30 +/-
      11.63 years, and the youngest was 17 years old and the oldest 92 years old. In
      the age composition of advanced schistosomiasis patients, the greatest number of
      cases was in the 60-70 years age group (32.72%). There were 3 595 cases of
      ascites type (62.83%), 2107 cases of splenomegaly type (36.82%), 11 cases of
      dwarf type (0.16%), and 11 cases of colon proliferation type (0.35%). CONCLUSION:
      The prevalence rate of advanced schistosomiasis is relatively stable in Hunan
      Province, and the age of the patients showed an old aging trend. The salvation of
      advanced schistosomiasis patients in non-endemic areas should be strengthened.

PMID- 25051828
TI  - [Cloning and expression of Schistosoma japonicum VCP gene and its mRNA expression
      levels in different stages].
AB  - OBJECTIVE: To prokaryotically express the valosin-containing protein (VCP) of
      Schistosoma japonicum, and analyze its VCP mRNA expressions in the cercaria,
      schistosomulum, adult worm (female and male worms) and egg. METHODS: RNA of S.
      japonicum eggs were extracted, and reversely transcribed into cDNA. The VCP gene
      of S. japonicum was amplified by using polymerase chain reaction (PCR), and
      subcloned into the prokaryotically expressed vector pET15b. The recombined
      plasmid was transformed into BL21 cells, and the expression of the target gene
      was induced with isopropyl-beta-D-thiogalactopyranoside (IPTG). The recombinant
      protein was yielded through the purification of inclusion body, and identified by
      using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The
      RNA (s) of cercaria, schistosomulum, female adult worm, male adult worm, and egg
      of S. japonicum were extracted, digested with DNase, purified, and reversely
      transcribed into cDNA. The mRNA expressions of the VCP gene in various
      developmental stages of S. japonicum were determined by using fluorescence-based
      quantitative real-time PCR. RESULTS: The VCP gene of S. japonicum was yielded by
      PCR amplification, and the recombinant protein was obtained through recombinant
      plasmid expression and purification of inclusion body. The highest VCP mRNA
      expression in S. japonicum cercaria was detected by the fluorescence-based
      quantitative real-time PCR, while low expressions were found in the
      schistosomulum, egg, female and male adult worms. CONCLUSION: The recombinant
      protein encoded by the VCP gene of S. japonicum is successfully obtained, and the
      VCP mRNA expression is determined in various developmental stages of S.
      japonicum.

PMID- 25051827
TI  - [Cloning and function analysis of high mobility group box 1 (HMGB1) protein of
      Schistosoma japonicum (Mainland strain)].
AB  - OBJECTIVE: To clone and express a high mobility group box 1(HMGB1) protein of
      Schistosomajaponicum (Mainland strain) and analyze its function. METHODS: The DNA
      fragment of open reading frame encoding Sj HMGB 1 protein was amplified by RT-PCR
      from the mRNA of S. japonicum worms, then it was subcloned into the expression
      vector pET28a(+) to form the recombinant expression plasmid SjHMGB1-pET28a. The
      recombinant expression plasmid was transformed into the component E. coli
      BL21(DE3), and the tranformant containing recombinant expression plasmid was
      induced with IPTG to express the recombinant protein SjHMGB1. The recombinant
      SjHMGB1 protein was purified by affinity chromatography with nickel chelating
      affinity chromatography agarose gel. The Gel retard experiment and animal
      immunization were performed to analyze the DNA binding capacity and the
      immunologic property of recombinant SjHMGB1. The expression levels of HMGB1 in
      different life cycle stages of S. japonicum were analyzed by Western bloting and
      RT-PCR. Female ICR mice were immunized with the recombinant SjHMGB1 protein and
      infected with 45 +/- 2 cercariae of S. japonicum after three immunizations. Forty
      two days post-infection, the worms and eggs of S. japonicum were recovered from
      the portal vein and liver tissue, respectively. The worm and egg reduction rates
      were calculated respectively. RESULTS: A 530 bp of specific DNA fragment was
      amplified from mRNA of S. japonicum by RT-PCR, which was the open reading frame
      (ORF) encoding SjHMGBlprotein confirmed by DNA sequencing analysis. The
      recombinant expression plasmid SjHMGB1-pET28a was constructed by cloning the ORF
      of SjHMGB1 into a expression vector pET28a(+). The bacterium transformants
      containing the recombinant plasmid expressed a soluble recombinant protein about
      28 kDa after induced by IPTG, and the recombinant SjHMGB1 protein was purified by
      nickel chelating affinity chromatography. The gel retard experiment showed that
      the recombinant SjHMGB1 protein could bind to both supercoiled DNA and linear
      DNA, and the recombinant protein immunized mice produced high titers of antiserum
      IgG. Western bloting indicated that the recombinant SjHMGB1 protein was
      recognized specifically by the S. japonicum-infected mice serum. Above results
      showed that the recombinant SjHMGB1 protein possessed both functional activity
      and immunogenicity as the natural protein. RT-PCR and Western blot results showed
      that SjHMGB1 was abundantly expressed in the adult and egg stages whereas barely
      detectable in the cercaria stage. The immune protection experiment showed that
      the recombinant SjHMGB1 induced mice to produce high titers of specific antibody
      IgG but failed to conduct an effective immune protection against S. japonicum.
      CONCLUSION: The gene encoding HMGB1 from S. japonicum and the soluble recombinant
      SjHMGB1 protein with natural functional activity are obtained, and the
      recombinant SjHMGB1 has a high immunogenicity but is not able to induce an
      effective immune protection against S. japonicum.

PMID- 25051829
TI  - [Expression characteristics of microRNA in mice with schistosomiasis and
      praziquantel treatment].
AB  - OBJECTIVE: To investigate the expression characteristics of miR-155 and miR-146a
      in mice with schistosomiasis and praziquantel (PZQ) treatment. METHODS: Totally
      40 BABL/c mice were divided into 4 groups: a normal group, a 6W infected group
      that were infected cutaneously with 10 Schistosoma japonicum cercariae for 6
      weeks, a 12W infected group that were infected cutaneously with 10 Schistosoma
      japonicum cercariae for 12 weeks, and a praziquantel treated group that were
      infected cutaneously with 10 Schistosomajaponicum cercariae and intragastrically
      administered with PZQ (300 mg/kg/day) for 1 day in 6 weeks post-infection and
      continuing surviving 6 weeks. The animals were sacrificed in 6 weeks and 12 weeks
      post-infection respectively. The left front lobe of each liver was stained with
      hematoxylin-eosin (HE) to detect pathological lesions. The levels of mRNA
      expressions of miR-155, miR-146a and pro-inflammatory cytokines (TNF-alpha, IL
      1beta and IL-6) in the liver tissue were determined by using quantitative real
      time PCR. RESULTS: The levels of mRNA expressions of miR-155, miR-146a and pro
      inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) in the 6W infected mice
      were significantly higher than those of the normal mice and of the 12W infected
      mice. Compared with the 12W infected mice, the inflammation response of liver egg
      granuloma in the PZQ-treated mice was ameliorated. Furthermore, there was a
      marked increase in the levels of mRNA expressions of miR-155, miR-146a and three
      pro-inflammatory cytokines in the PZQ-treated mice compared to the 12W infected
      mice. CONCLUSION: miR-155 and miR-146a may play a role in schistosomiasis liver
      inflammation response and the inflammation regulation of praziquantel treatment.

PMID- 25051830
TI  - [Dynamic expressions of IL-22 and hepatic stellate cells senescence in mice
      infected with Schistosoma japonicum].
AB  - OBJECTIVE: To investigate the dynamic expressions of interleukin-22 (IL-22) ,
      Interleukin-22 receptor 1 (IL-22R1), and hepatic stellate cells (HSC) senescence
      in mice with Schistosoma japonicum infection. METHODS: A murine model of S.
      japonicum infection was established and the serum samples and liver tissues were
      collected 4, 6, 8, 12 weeks post-infection. The serum samples were detected for
      the levels of alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST). The pathological changes and proliferation of hepatic collagen fibers in
      the liver tissue were observed after HE staining and Masson staining. The HSC
      senescence in fibrotic livers was determined by the detection of senescence
      associated beta-galactosidase (SA-beta-Gal). Sandwich ELISA was used to measure
      the expressions of IL-22, and Real-time PCR was used to test the mRNA levels of
      IL-22 and IL-22R1. The control group without S. japonicum infection was set up.
      RESULTS: The serum levels of ALT and AST significantly increased 8 weeks and 12
      weeks after the infection (vs. 0 week, all P < 0.05). The level of IL-22
      increased 4 weeks and 6 weeks after the infection (vs. 0 week, both P < 0.05),
      but reduced 8 weeks post-infection, and was even lower 12 weeks post-infection
      (vs. 4 weeks and 6 weeks, both P < 0.01). Being consistent with the dynamic
      expression of IL-22 protein, the mRNA expression of IL-22 began to increase 4
      weeks and reached the peak 6 weeks after the infection (vs. 0 week, both P <
      0.05), and continuously declined 8 weeks and 12 weeks post-infections (vs. 6
      weeks, both P< 0.05). The increase of the expression of IL-22R1 mRNA was
      correlated with the progression of fibrosis, and the peak was in 12 weeks post
      infections (vs. 0 week and 6 weeks, both P < 0.05). The number of senescence
      associated beta-galactosidase-positive HSCs was reduced with the decreasing
      expression of IL-22 in the advanced liver fibrosis. CONCLUSION: IL-22 and IL-22R1
      are involved in the pathogenesis of schistosomiasis liver fibrosis. As an
      inflammation factor, IL-22 significantly increases in the early stage of
      fibrosis. The expression of IL-22 decreases in the late stage of fibrosis, which
      may contribute to HSC senescence and restrict liver fibrosis.

PMID- 25051831
TI  - [Comparative analysis of mitochondrial genomes of Angiostrongylus cantonensis].
AB  - OBJECTIVE: To compare the diversity of mitochondrial genomes of Angiostrongylus
      cantonensis in the mainland of China. METHODS: According to the population
      genetic of A. cantonensis, seven female worms were selected to characterize the
      mitochondrial (MT) genomes. Twelve primer pairs based on known MT genome
      (GQ398121) were used for PCR. The target fragments were sequenced and aligned.
      The gene localization, genome structure, composition of nucleotide, distribution
      of variable sites, and phylogeny were analyzed by employing multiple softwares.
      RESULTS: Five distinct types were identified from seven complete MT genomes. They
      were similar in size and structure, i.e., ranging 13,491-13,502 bp, including 12
      protein-coding genes, 2 ribosomal genes, 22 tRNA genes, and 2 major non-coding
      regions. All the genes were localized at the same strand and had the same
      transcription direction. A total of 745 variable sites were identified,
      accounting for 5.5%. Among the variable sites, 59 were deletion/insert mutations,
      105 transversions, and 581 transitions. The variable sites distributed evenly at
      the complete genome. CONCLUSION: The study reveals the mutation profile in the
      whole MT genome of A. cantonensis and thus will facilitate the development of
      intraspecific differential diagnosis.

PMID- 25051832
TI  - [A case of fasciolasis hepatic in Zunyi City, Guizhou Province].
AB  - Four adults of Fasciola hepatica were found from the bile ducts of a patient
      diagnosed as biliary calculi during a surgical operation. We investigated
      retrospectively the infection source and concluded that the patient may be
      infected by eating raw or half-cooked Zizania latifolia, an aquatic plant, which
      was contaminated with metacercariae of F. hepatica.

PMID- 25051833
TI  - [Cluster analysis of cystic echinococcosis in non Tibetan Plateau regions].
AB  - OBJECTIVE: To understand the endemic characteristics and regularity of cystic
      echinococcosis by evaluating and classifying its endemic situation in Non Tibetan
      Plateau regions, so as to provide the evidence for formulating effective
      preventive and control measures. METHODS: The prevalence data of cystic
      echinococcosis in 174 counties (cities, districts, banners) in Non Tibetan
      Plateau regions from a national survey were collected and analyzed by the sample
      cluster method in 2012. RESULTS: The 174 counties (cities, districts, banners)
      could be classified into 4 clusters by spatial distribution. The first cluster
      with human high prevalence rate, low infection rate of livestock, and positive
      rate of dog stool antigen included 3 counties. The second cluster with high
      infection rate of livestock, low prevalence rate of human, and positive rate of
      dog stool antigen included 20 counties (cities). The third cluster with high
      positive rate of dog stool antigen, low prevalence rate of human, and low
      infection rate of livestock included 39 counties (cities, districts, banners).
      The fourth cluster with low rates of the above 3 indices included the rest 112
      counties. CONCLUSIONS: The results of the cluster analysis conform to the current
      epidemiological status of cystic echinococcosis in the Non Tibetan Plateau
      regions. The epidemiological characteristics and geographical distributions of
      the four area types will provide a basis for the classified management and
      guidance of cystic echinococcosis control in these areas.

PMID- 25051834
TI  - [Longitudinal observations on effect of schistosomiasis control in Gongan County,
      Hubei Province].
AB  - OBJECTIVE: To evaluate the effect of schistosomiasis control in Gongan County,
      Hubei Province by longitudinal observations so as to provide the evidence for
      formulating the schistosomiasis control strategy in lake and marshland regions.
      METHODS: The schistosomiasis epidemic data in Gongan County from 2000-2013 were
      collected by the retrospective research method, and analyzed about the changing
      tendency of human and cattle infection rates, and Oncomelania hupensis snail
      situation. RESULTS: The tendency of schistosomiasis epidemic situation was
      descended from 2000 to 2013. The human infection rate declined from 12.62% in
      2000 to 0.69% in 2013. The decline scope of human infection rate was 24.1% in the
      first stage, 64.4% in the second stage, and 73.0% in the third stage. Eight acute
      schistosomiasis cases were reported in the first stage, 15 cases in the second
      stage, and none in the third stage. The cattle infection rate declined from 6.50%
      in 2000 to 0.30% in 2013. The rise scope of cattle infection rate was 74.2% in
      the first stage, but the decline scope was 75.0% in the second stage and 87.6% in
      the third stage. All the cattle were disposal at the end of 2013. The infection
      rate of snails, area with infected snails, and average density of living snails
      in the first stage increased by 18.1%, 46.0% and 7.6%, respectively. The 3
      indexes above-mentioned in the second stage decreased by 76.8%, 97.8% and 37.9%,
      respectively. In the third stage, the infection rate of snails and area with
      infected snails decreased by both 100%, but the average density of living snails
      increased by 2.7%. The infected snails were found from 2000 to 2011, but none in
      2012 and 2013. The infection rate of snails and area with infected snails dropped
      yearly, the infection rate of snails declined from 0.0007% in 2000 to 0.0002% in
      2011, and the area with infected snails declined from 267.8 hm2 in 2000 to 6.37
      hm2 in 2011. CONCLUSION: After the implementation of the integrated
      schistosomiasis prevention and control strategy with the emphasis on infectious
      source control, the human and cattle schistosome infection rates decline
      significantly. Hereafter, it is necessary to prevent the schistosomiasis epidemic
      outbreak or rebound.

PMID- 25051836
TI  - [Cost-benefit analysis of netting cultivation to block the spread of Oncomelania
      snails in lake regions].
AB  - OBJECTIVE: To evaluate the cost-benefit of netting cultivation to block the
      spread of Oncomelania snails in lake regions. METHODS: The cost-benefit of
      netting cultivation was investigated by interviewing in the field, the cost of
      Oncomelania snail survey and control was investigated by retrospective review in
      Gaoyou Lake regions of Jinhu County from 2009 to 2011. The benefit of netting
      cultivation to block the spread of snails in lake regions was calculated by the
      benefit-cost ratio (BCR), and then the cost-benefit of them was calculated.
      RESULTS: The area of netting cultivation in Gaoyou Lake regions was 70.77 hm2,
      the average cost of netting cultivation was 495,595 yuan every year, the average
      income was 962,000 yuan every year, and the average benefit of netting
      cultivation was 466 405 yuan. The average cost of Oncomelania snail survey and
      control from 2009 to 2011 was 85,047.87 yuan in Gaoyou Lake regions. The ratio of
      cost-benefit was 1.11:1. The benefit was more than the cost. CONCLUSION: There is
      a well benefit in lake regions during blocking the spread of snails by netting
      cultivation.

PMID- 25051835
TI  - [Jatropha seed oils extracted by different methods and their effect on killing
      cercaria of Schistosoma japonicum].
AB  - OBJECTIVE: To evaluate the effect of Jatropha seed oils extracted by different
      methods on killing cercaria of Schistosomajaponicum so as to screen the optimum
      process and formulations. METHODS: The cercaria directly contacting tests with
      Jatropha seed oils extracted by 6 different extraction processes were carried
      out, and the mouse immediate contacting cercaria infection trials with different
      formulations of Jatropha seed oil and various additives were performed. RESULTS:
      With 95% ethanol, the ratio of material to liquid being 1:8, and 2 h extraction,
      the oil extraction rate was 30.7%. The cercaria directly contacting tests showed
      that 6 kinds of Jatropha seed oil killed all cercaria within 30 min. In the mouse
      immediate contacting cercaria infection trials, the worm declined rate of
      Jatropha seed oil liquid was 70.97%, and the worm declined rate of the sample
      added with benzyl benzoate was 58.87%, and the worm declined rate of the sample
      added with laurocapram was 77.42%. The worm declined rate of the samples added
      with benzyl benzoate, dibutyl phthalate and laurocapram was 100%. CONCLUSION: The
      process with 95% ethanol, the ratio of material to liquid being 1:8, and 2 h
      extraction is the optimum, and the Jatropha seed oil has a good killing
      schistosome cercaria effect.

PMID- 25051837
TI  - [Investigation on field feces in schistosomiasis endemic areas in Jingzhou City].
AB  - OBJECTIVE: To understand the status of field feces in Jingzhou City, so as to
      provide the evidence for improving the control measures to interrupt the
      transmission routes of schistosomiasis. METHODS: The distribution of field feces
      was investigated in 27 schistosomiasis endemic villages in Gong' an, Jianli,
      Jiangling, Honghu and Shishou counties (cities) from 2010 to 2012. The
      schistosome positive status of the field feces was surveyed with the hatching
      method. RESULTS: There were 1366 field feces and the average density was 0.0892
      feces per 100 square meters in this survey. The cattle feces, human feces, dog
      feces and elk feces respectively accounted for 99.71%, 0.07%, 0.15% and 0.07% in
      the survey. The infection rates of the field feces were 1.46% and 2.42% in the
      channels and bottomlands, respectively (P > 0.05). The average rate of infected
      field feces was 3.21% in 2010, 0.36% in 2011, and 1.60% in 2012, and the
      difference between 2010 and 2012 was not statistically significant (P > 0.05).
      CONCLUSIONS: The main field feces come from cattle, and the main distribution of
      infected field feces is in channels and bottom-lands. Therefore, the management
      of cattle and treatment of field feces should be strengthened.

PMID- 25051838
TI  - [Influencing factors in elderly patients with schistosomiasis liver disease
      combined with gallbladder diseases].
AB  - OBJECTIVE: To understand the status of elderly patients with schistosomiasis
      liver diseases combined with gallbladder diseases, and explore the influencing
      factors. METHODS: A total of 280 elderly patients with schistosomiasis liver
      disease were divided into two groups, 198 cases of chronic liver fibrosis and 82
      cases of liver cirrhosis, and the results of their gallbladder ultrasound and
      liver function examinations were analyzed statistically. RESULTS: Among the 280
      cases, 157 patients were combined with gallbladder diseases (56.1%), including
      gallbladder wall thickening (28.2%, 79/280), cholecystolithiasis (13.6%, 38/
      280), cholecystitis (11.1%, 31/280), and gallbladder polyp (3.2%, 9/280). The
      incidence rates of gallbladder wall thickening, cholecystitis and
      cholecystolithiasis in the schistosomiasis patients with cirrhosis were
      significantly higher than those in the schistosomiasis patients with liver
      fibrosis (chi2 = 4.568, P < 0.05). CONCLUSION: The main influencing factors of
      schistosomiasis liver disease combined with gallbladder diseases are the age, the
      course of the disease, liver cirrhosis and the portal hypertension degree.

PMID- 25051839
TI  - [Curative effect of Ruangan pills in treatment of schistosomiasis liver
      fibrosis].
AB  - OBJECTIVE: To explore the efficacy, mechanism and safety of silibinin combined
      with Ruangan pills (a Chinese herbal preparation) in the treatment of
      schistosomiasis liver fibrosis. METHODS: A total of 200 patients with
      schistosomiasis liver fibrosis were randomly divided into a control group and a
      treatment group, and 100 patients in each group were respectively administered
      with oral silibinin alone and oral silibinin combined with Ruangan pills,
      respectively. The curative effects in the two groups were evaluated in 3 months,
      6 months, 9 months and 12 months respectively. RESULTS: The common five clinical
      symptoms of schistosomiasis liver fibrosis patients significantly relieved in the
      treatment group 12 months after the therapy, and the total efficiency reached
      more than 75%, which were significantly higher than that in the control group. In
      the treatment group and the control group, there was no improvement in the liver
      B ultrasonic classification 3 months and 6 months after the therapy (P > 0.05);
      however, in 9 months and 12 months, the liver B ultrasonic classification in the
      treatment group was better than that in the control group (P < 0.05, P < 0.01,
      respectively). For the four serum indexes of liver fibrosis, there was no
      significant differences between the two groups in 3 months, however, in 6 months,
      9 months, and 12 months, there was a significant improvement in the treatment
      group compared with the control group. There were no obviously adverse effects in
      two groups. CONCLUSION: Silibinin combined with Ruangan pills has a better
      curative effect in the treatment of schistosomiasis liver fibrosis.

PMID- 25051840
TI  - [Prevalence of malaria in Liaoning Province, 2008 to 2013].
AB  - OBJECTIVE: To understand the trend and epidemiologic characteristics of malaria
      prevalence so as to provide the evidence for further control of the disease in
      Liaoning Province. METHODS: The data of registered cases of malaria in Liaoning
      Province from 2008 to 2013 were collected and analyzed with the descriptive
      epidemiological methods. RESULTS: A total of 202 malaria cases were reported from
      2008 to 2013. There was no epidemic outbreak, and the average annual incidence
      was 0.08/ 100,000. Totally 17 P. v. cases of local infection were reported, and
      185 imported malaria cases were reported (P.v. 33 cases, P.f 113 cases, P.v. &
      Pf. 13 cases, P.o. 3 cases, and unspecified 23 cases). The ratio of male to
      female was 5.91:1, the populations aged 31-45 years were the most (47.52%), and
      the main occupation was exported labors (46.04%). The 179 imported cases were
      infected in Africa and Southeast Asia, 6 imported cases were infected in Anhui
      Province, Yunnan Province and Hongkong, and 16 local cases were infected in the
      border area of Dandong City. CONCLUSIONS: Although the annual incidence of
      malaria in Liaoning Province is lower than 1/10,000, the incidence shows an
      increasing trend because the exported labors are increased. Therefore, the
      epidemic monitoring and health education should be strengthened, especially for
      the exported labors who have returned.

PMID- 25051841
TI  - [Analysis of results of technique competition for diagnosis of parasitic diseases
      in Shandong Province].
AB  - OBJECTIVE: To understand the capacity of Plasmodium detection and helminth
      detection and the mastery degree of basic knowledge of parasitic diseases.
      METHODS: Three professionals from each city were selected as contestants. The
      content of the competition contained three parts. The first part included making
      blood slides and Giemsa staining of Plasmodium, and identification of species and
      number with microscopy, the second part included making stool slides with Kato
      Katz technique and identification of common helminth eggs with microscopy, and
      the third part was basic knowledge of parasitic diseases. RESULTS: Totally 51
      contestants took part in the competition. The average score of the test of making
      blood slides was 14.8 +/- 3.3, and the passing rate was 82.4%. The average score
      of the identification of species and number of Plasmodium with microscopy was
      19.2 +/- 9.3, and the passing rate was 29.4%. The average score of the test of
      making stool slides was 9.3 +/- 0.7, and the passing rate was 100%. The average
      score of the identification of common helminth eggs with microscopy was 28.0 +/-
      2.6, and the passing rate was 100%. The average score of basic knowledge of
      parasitic diseases was 76.3 +/- 11.9, and the passing rate was 88.2%. The average
      score of the test of making blood slides in the female was higher than that in
      the male (15.7vs.13.5, P < 0.05), and the average score of the test of making
      blood slides in the intermediate title contestants was higher than that in the
      junior title contestants (16.1 vs.14.1, P < 0.05). The average score of the basic
      knowledge of parasitic diseases in the contestants from cities was higher than
      that in the contestants from towns (83.2 vs. 72.6, P < 0.05), and the average
      score of basic knowledge of parasitic diseases in the contestants from high
      economic level cities was higher than that in the contestants from low economic
      level cities (82.4 vs. 71.5, P < 0.01). CONCLUSIONS: For professionals in
      Shandong Province, the capacity of helminth detection was strong and the basic
      knowledge of parasitic diseases was mastered well, while the capacity of
      Plasmodium detection was weak.

PMID- 25051842
TI  - [Schistosomiasis status and control strategy in Hubei Province from 2008 to
      2012].
AB  - OBJECTIVE: To evaluate the effects of the schistosomiasis control mode ("Hubei
      mode") that includes "comprehensive measures in a whole endemic county", "co
      action of Health Ministry and Province" and "replacing cattle with machine" in
      Hubei Province. METHODS: The data of schistosomiasis control in Hubei Province
      from 2008 to 2012 were collected and a database including the annual schistosome
      infections of human and cattle, acute schistosome infection, outbreak of
      schistosomiasis endemic, schistosome infected Oncomelania hupensis snails, and
      other prevention indicators was established and analyzed by using SPSS. RESULTS:
      Compared with 2008, in 2012, the infection rates declined by 64.91% and 88.63% in
      human and cattle respectively. The area with snails decreased from 5423.85 hm2 in
      2008 to zero. There were no acute schistosomiasis patients and outbreak of
      schistosomiasis endemic. CONCLUSION: The schistosomiasis control mode ("Hubei
      mode") is effective significantly.

PMID- 25051843
TI  - [Epidemic situation and prevention strategy of schistosomiasis in Ya' an City
      after Lushan Earthquake on April 20, 2013].
AB  - This paper analyzes the recently epidemic status of schistosomiasis, the change
      of natural and social factors, and field survey and evaluation data of
      schistosomiasis in Ya'an City after Lushan Earthquake on April 20, 2013, and
      proposes that it is necessary to strengthen the conventional schistosomiasis
      control measures, the control of exogenous infection sources, the control of
      Oncomelania hupensis snails and health education for ensuring no major epidemics
      after the disaster. This paper also recommends the direction and suggestions for
      future schistosomiasis control in Ya' an City.

PMID- 25051844
TI  - [SWOT analysis of laboratory certification and accreditation on detection of
      parasitic diseases].
AB  - This study analyzes the strength, weakness, opportunity and threat (SWOT) of
      laboratory certification and accreditation on detection of parasitic diseases by
      SWOT analysis comprehensively, and it puts forward some development strategies
      specifically, in order to provide some indicative references for the further
      development.

PMID- 25051845
TI  - [Discovery and biology of Schistosoma haematobium].
AB  - Schistosomiasis is a neglected tropical disease that severely threatens human
      health and affects the socioeconomic development. The causative agent that
      parasitizes in humans mainly involves Schistosoma japonicum, S. mansoni, S.
      haematobiurn, S. intercalatum and S. mekongi. As the firstly identified
      schistosome, S. haematobium infection is found to strongly correlate with bladder
      cancer. This paper mainly reviews the discovery, morphology and life cycle of S.
      haematobium.

PMID- 25051846
TI  - [Analysis of schistosomiasis epidemic situation in Xinjiangkou Township, Sonzi
      City, from 2004 to 2013].
AB  - OBJECTIVE: To master the status of schistosomiasis transmission in Xinjiangkou
      Township, Sonzi City, from 2004 to 2013. METHODS: The data of schistosomiasis
      epidemic situation were collected and analyzed statistically in Xinjiangkou
      Township, Sonzi City, from 2004 to 2013. RESULTS: From 2004 to 2013, the areas
      with Oncomelania hupensis snails were 193.2-185.3 hm2, and the highest density of
      infected living snails was 0.00070 snail/0.1 m2 in 2007. However, after 2011, no
      infected living snails were found. The positive rate of blood tests was 9.46% and
      schistosomiasis infection rate was 7.36% in 2005, and the positive rate of blood
      tests was 3.27% and schistosomiasis infection rate was 0.57% in 2013. There were
      7 cases of acute schistosomiasis in 2004 and 2005, respectively, and there were
      no acute schistosomiasis patients after 2006. The schistosome infection rate of
      cattle was 18.27% in 2004, and after 2007, the infection rate decreased below 5%.
      In 2013, all the cattle were obsoleted. CONCLUSION: The schistosomiasis
      transmission has reduced to a low level in Xinjiangkou Township. However, to
      realize the aim of schistosomiasis transmission controlled, the comprehensive
      control measures mainly based on infectious source control should still be
      strengthened.

PMID- 25051847
TI  - [Investigation on pregnancy outcomes and risk factors in pregnant women infected
      with Toxoplasma gondii].
AB  - OBJECTIVE: To understand the pregnancy outcomes and risk factors in pregnant
      women infected with Toxoplasma gondii. METHODS: Toxoplasma IgM and IgG antibodies
      in sera from 2 740 cases of pregnant women were detected by using enzyme -linked
      immunosorbent assay (ELISA) in Zhuozhou Municipal Maternal and Child Health Care
      Center from 2010 to 2013, and the pregnancy outcomes were followed up. The risk
      factors for Toxoplasma infection were investigated with questionnaires. RESULTS:
      Among the 2 740 cases of pregnant women, 195 cases were found with antibodies to
      T. gondii (7.12%), and among them, 44 cases were IgM positive (22.56%), and 151
      cases were IgG positive (77.44%). There were 41 cases with adverse pregnancy
      outcomes among the 195 cases (21.02%), including 32 cases of IgM positive
      (78.05%) and 9 cases of IgG positive (21.95%). There were 6 cases of adverse
      pregnancy outcomes in uninfected pregnant women (2.86%). The difference between
      the two groups was statistically significant (P < 0.05). The close contact with
      animals, eating raw meat, eating chafing dish or barbeque, and eating raw meat
      stuffing were important risk factors in pregnant women infected with T. gondii
      (compared with the uninfected group, P < 0.01). CONCLUSION: The Toxoplasma
      infection may lead to adverse pregnancy outcomes, therefore, to develop good
      habits of life and health is an effective way to avoid adverse pregnancy
      outcomes.

PMID- 25051848
TI  - [Clinical efficacy of sodium tanshinone IIA sulfonate in treatment of advanced
      schistosomiasis].
AB  - OBJECTIVE: To evaluate the clinical efficacy of sodium tanshinone IIA sulfonate
      (STS) in the treatment of advanced schistosomiasis. METHODS: Fifty cases with
      advanced schistosomiasis admitted to the Touzao Township Hospital of Dongtai City
      during the period from November 2012 to November 2013 were treated with STS for
      10 days, and the internal diameter of the portal vein, levels of ALT, AST, gamma
      GT, PIIIP, CIV, HA and LN were measured and compared before and after the
      administration of STS. RESULTS: The mean levels of all serological parameters
      except HA were within the normal range before STS treatment, while the highest
      positive rate was detected in gamma-GT (26.0%) and HA (54.0%). Following the STS
      treatment, the mean levels of all parameters and the positive rates reduced, with
      the greatest reduction observed in gamma-GT (36.7%) and HA (37.8%); however, the
      mean HA level was still higher than the normal range. The mean internal diameter
      of the portal vein reduced from (10.5 +/- 1.7) mm before the STS treatment to
      (9.8 +/- 1.3) mm after the STS administration, with a significant diffrtence (P <
      0.05). CONCLUSION: STS appears effective in the treatment of advanced
      schistosomiasis.

PMID- 25051849
TI  - [Risk factors of schistosomiasis cirrhosis esophageal varices bleeding].
AB  - OBJECTIVE: To explore the risk factors of schistosomiasis cirrhosis esophageal
      varices hemorrhage. METHODS: A total of 113 cases of schistosomiasis cirrhosis
      esophageal varices hemorrhage and 128 schistosomiasis cirrhosis esophageal
      varices patients without hemorrhage were selected and their relevant factors were
      analyzed statistically. RESULTS: There were significant differences between the
      two groups in the prothrombin time, portal vein diameter, degree of esophageal
      varices, and varicose vein tumor-like lesions (P < 0.01). CONCLUSION: The risk
      factors of schistosomiasis cirrhosis esophageal varices hemorrhage are the
      prothrombin time, portal vein diameter, degree of esophageal varices, and
      varicose vein tumor-like lesions.

PMID- 25051850
TI  - [Investigation on common human soil-transmitted nematode infections in Quanzhou
      City in 2012].
AB  - OBJECTIVE: To understand the epidemic situation of common human soil-transmitted
      nematode infections in Quanzhou City in 2012, so as to provide the evidence for
      improving the prevention and control measures. METHODS: The residents aged above
      3 years from 5 townships in 2 counties were investigated to detect the parasite
      eggs (hookworm, Ascaris lumbricoides, Trichuris trichura) by Kato-Katz technique.
      One kindergarten of each county was randomly selected and 228 children were
      investigated to detect Enterubius vermicularis eggs by the cellophane tape anus
      test. RESULTS: The total hookworm infection rate was 3.60% (69/1919). For the
      hookworm infection rates, there was no significant difference among different
      areas and between different genders, but there were significant differences among
      different age groups and different careers. No Enterubius vermicularis eggs were
      detected. CONCLUSION: The effect of the prevention and control of Ascaris
      lumbricoides, Trichuris trichura and Enterubius vermicularis infections is
      remarkable. However, the infection rate of hookworm has a rising trend and the
      prevention and control of hookworm infection should be strengthened.

PMID- 25051851
TI  - [Laparoscopic surgical treatment for schistosomiasis liver fibrosis portal
      hypertension combined with calculous cholecystitis].
AB  - OBJECTIVE: To evaluate the curative effect of laparoscopic cholecystectomy (LC)
      in the treatment of schistosomiasis liver fibrosis portal hypertension combined
      with calculous cholecystitis. METHODS: The clinical data of 196 cases of
      schistosomiasis liver fibrosis portal hypertension combined with calculous
      cholecystitis (Child A 160 cases, Child B 36 cases) treated with LC were
      collected and analyzed from June 2006 to June 2013. RESULTS: Among the 196 cases,
      there were 154 cases of schistosomiasis liver fibrosis portal hypertension
      combined with chronic calculous cholecystitis, and 42 cases of schistosomiasis
      liver fibrosis portal hypertension combined with acute calculous cholecystitis.
      Totally 189 patients underwent LC successfully, but 7 were transited to the
      general operation because of LC failure, including 3 cases of adhesion around
      gallbladder and ambiguous dissection of gallbladder triangle, and 4 cases of
      intraoperative bleeding and the bleeding was difficult to stop under the
      laparoscopy. All the 196 patients were cured. CONCLUSION: LC is effective and
      safe in the treatment of schistosomiasis liver fibrosis portal hypertension
      combined with calculous cholecystitis.

PMID- 25051852
TI  - [Two cases of African imported Plasmodium malariae malaria].
AB  - The process of diagnosis, epidemiological survey and treatment of two cases of
      African imported quartan malaria is reported in this paper.

PMID- 25051853
TI  - [A cecum hookworm patient with main symptom of cough].
AB  - This paper reports a cecal hookworm patient whose main symptoms are dry cough,
      dyspnea and eosinophilia.

PMID- 25051854
TI  - Manage your team's collective time.

PMID- 25051855
TI  - 21st-Century talent spotting.
AB  - How can a person who seems so qualified for a position fail miserably in it? How
      can someone who clearly lacks relevant skills and experience succeed? The answer
      is potential, the ability to adapt and grow into increasingly complex roles and
      environments. For the past several decades, organizations have based their hiring
      decisions on competencies. But we have entered a new era of talent spotting.
      Geopolitics, business, industries, and jobs are changing so rapidly that it's
      impossible to predict the capabilities employees and leaders will need even a few
      years out. The question now is not whether people have the right skills; it's
      whether they have the potential to learn new ones. Research points to five
      markers of potential: a strong motivation to excel in the pursuit of challenging
      goals combined with the humility to put the group ahead of individual needs; an
      insatiable curiosity to explore new ideas and avenues; keen insight into
      connections that others don't see; a strong engagement with work and people; and
      the determination to overcome obstacles. Once organizations have hired true high
      potentials--a challenge, given the increasing scarcity of senior talent-and
      identified the ones they already have, it's crucial to focus on retaining them
      and on helping them live up to their potential by offering development
      opportunities that push them out of their comfort zones.

PMID- 25051856
TI  - Managing investors.
AB  - Managers and academics often lament that Wall Street's shortterm focus makes it
      impossible for corporations to plan for the long run. Palmisano disagrees. Yes,
      there are some on Wall Street, such as the sell-side analysts who dominate
      quarterly earnings conference calls, who can't see more than a few months out.
      But CEOs shouldn't participate in those calls anyway, he believes. They should
      instead focus their energies on the institutional investors who will embrace the
      long view if they are given ways to judge a company's progress. In this edited
      interview with one of HBR's executive editors, Palmisano describes how IBM's top
      management made significant changes to how the firm set goals and communicated
      them to investors. "The model," a rolling multi-year road map for earnings growth
      and cash generation, included an emphasis on R&D investment even during
      downturns, a plan for execution that involved every unit in the organization, and
      a shift toward long-term compensation. Transparency and open dialogues with large
      shareholders were also key. The CEO is a steward, Palmisano argues, charged with
      protecting a company and its returns for decades to come. But that vision need
      not clash with success on the visible horizon; during Palmisano's tenure, IBM's
      stock price soared.

PMID- 25051857
TI  - Mastering the intermediaries.
AB  - Almost every retailer looks to Google to refer customers, and it's rare to find a
      manufacturer whose products aren't sold on Amazon. But these and other big
      platforms can capture a disproportionate share of the value a company creates:
      Buy an app on iTunes, and Apple takes 30%. The author presents four strategies to
      help businesses reduce their dependence on powerful platforms. Exploit the
      platform's need to be comprehensive. American Airlines' strong coverage of key
      routes made its presence on the travel website Kayak indispensable to Kayak's
      value proposition. As a result, AA negotiated a better deal. Identify and
      discredit discrimination. Public complaints that eBay was giving search
      prominence to suppliers who advertised on the site forced a reversal of the
      policy. Create an alternative platform. When MovieTickets was on the verge of
      dominating phone and online ticketing, Regal Entertainment and two other large
      theater chains formed Fandango. Deal more directly. People ordering takeout
      through online platforms like Foodler and GrubHub have often already chosen their
      restaurant. Restaurants that deal directly can exit the platform.

PMID- 25051858
TI  - Collective genius.
AB  - How can leaders build an organization that is capable of innovating continually
      over time? By creating a community that is both willing and able to innovate. To
      be willing, the community must share a sense of purpose, values, and rules of
      engagement. When Luca de Meo was Volkswagen's head of marketing communication, he
      fostered a sense of purpose in his team by asking its members to reflect on what
      being part of VW meant to them; strengthened their shared values by encouraging
      them to use the brand's three components-innovation, responsibility, and value-to
      guide their work; and built significant responsibility and autonomy into their
      rules of engagement. To be able, companies must generate ideas through discourse
      and debate; experiment quickly, reflect, and adjust; and make decisions that
      combine disparate and even opposing ideas. Bill Coughran, an SVP of engineering
      at Google, employed these capabilities both to solve the company's near-term data
      storage needs and to make progress toward a next-generation solution.

PMID- 25051859
TI  - Engaging doctors in the health care revolution.
AB  - A health care revolution is under way, and doctors must be part of it. But many
      are deeply anxious and angry about the transformation, fearing loss of autonomy,
      respect, and income. Given their resistance, how can health system Leaders engage
      them in redesigning care? In this article, Dr. Thomas H. Lee, Press Ganey's chief
      medical officer, and Dr. Toby Cosgrove, the CEO of the Cleveland Clinic, describe
      a framework they've developed for encouraging buy-in. Adapting Max Weber's
      "typology of motives," and applying behavioral economics and other motivational
      principles, they describe four tactics leadership must apply in concert: engaging
      doctors in a noble shared purpose; addressing their economic self-interest;
      leveraging their desire for respect; and appealing to their sense of tradition.
      Drawing from experiences at the Mayo Clinic, Geisinger Health System, Partners
      HealthCare, the Cleveland Clinic, Ascension Health, and others, the authors show
      how the four motivational levers work together to bring this critical group of
      stakeholders on board.

PMID- 25051860
TI  - Career choices when life is short.

PMID- 25051862
TI  - Shinseki (still) must go.

PMID- 25051861
TI  - What you need to know about MERS. A dangerous new disease has gone global.

PMID- 25051863
TI  - A preemie revolution.

PMID- 25051864
TI  - Introduction: Values and norms in modeling.

PMID- 25051865
TI  - Making the abstract concrete: the role of norms and values in experimental
      modeling.
AB  - Experimental modeling is the construction of theoretical models hand in hand with
      experimental activity. As explained in Section 1, experimental modeling starts
      with claims about phenomena that use abstract concepts, concepts whose conditions
      of realization are not yet specified; and it ends with a concrete model of the
      phenomenon, a model that can be tested against data. This paper argues that this
      process from abstract concepts to concrete models involves judgments of
      relevance, which are irreducibly normative. In Section 2, we show, on the basis
      of several case studies, how these judgments contribute to the determination of
      the conditions of realization of the abstract concepts and, at the same time, of
      the quantities that characterize the phenomenon under study. Then, in Section 3,
      we compare this view on modeling with other approaches that also have
      acknowledged the role of relevance judgments in science. To conclude, in Section
      4, we discuss the possibility of a plurality of relevance judgments and introduce
      a distinction between locally and generally relevant factors.

PMID- 25051866
TI  - Values in design sciences.
AB  - Following Herbert Simon's idea of "the sciences of the artificial", one may
      contrast descriptive sciences and design sciences: the former are concerned with
      "how things are", the latter tell us "how things ought to be in order to attain
      goals, and to function". Typical results of design sciences are thus expressions
      about means--ends relations or technical norms in G. H. von Wright's sense.
      Theorizing and modeling are important methods of giving a value-free epistemic
      justification for such technical norms. The values of design sciences are not
      criteria for the acceptance of theories or models, but rather antecedents of
      conditional recommendations of actions. Design sciences are thus value-neutral
      and value-laden at the same time.

PMID- 25051867
TI  - Accountability and values in radically collaborative research.
AB  - This paper discusses a crisis of accountability that arises when scientific
      collaborations are massively epistemically distributed. We argue that social
      models of epistemic collaboration, which are social analogs to what Patrick
      Suppes called a "model of the experiment," must play a role in creating
      accountability in these contexts. We also argue that these social models must
      accommodate the fact that the various agents in a collaborative project often
      have ineliminable, messy, and conflicting interests and values; any story about
      accountability in a massively distributed collaboration must therefore involve
      models of such interests and values and their methodological and epistemic
      effects.

PMID- 25051868
TI  - Values and uncertainties in climate prediction, revisited.
AB  - Philosophers continue to debate both the actual and the ideal roles of values in
      science. Recently, Eric Winsberg has offered a novel, model-based challenge to
      those who argue that the internal workings of science can and should be kept free
      from the influence of social values. He contends that model-based assignments of
      probability to hypotheses about future climate change are unavoidably influenced
      by social values. I raise two objections to Winsberg's argument, neither of which
      can wholly undermine its conclusion but each of which suggests that his argument
      exaggerates the influence of social values on estimates of uncertainty in climate
      prediction. I then show how a more traditional challenge to the value-free ideal
      seems tailor-made for the climate context.

PMID- 25051869
TI  - The morals of model-making.
AB  - I address questions about values in model-making in engineering, specifically:
      Might the role of values be attributable solely to interests involved in
      specifying and using the model? Selected examples illustrate the surprisingly
      wide variety of things one must take into account in the model-making itself. The
      notions of system (as used in engineering thermodynamics), and physically similar
      systems (as used in the physical sciences) are important and powerful in
      determining what is relevant to an engineering model. Another example (windfarms)
      illustrates how an idea to completely re-characterize, or reframe, an engineering
      problem arose during model-making. I employ a qualitative analogue of the notion
      of physically similar systems. Historical cases can thus be drawn upon; I
      illustrate with a comparison between a geoengineering proposal to inject, or
      spray, sulfate aerosols, and two different historical cases involving the
      spraying of DDT (fire ant eradication; malaria eradication). The current
      geoengineering proposal is seen to be like the disastrous and counterproductive
      case, and unlike the successful case, of the spraying of DDT. I conclude by
      explaining my view that model-making in science is analogous to moral perception
      in action, drawing on a view in moral theory that has come to be called moral
      particularism.

PMID- 25051870
TI  - Modeling for fairness: A Rawlsian approach.
AB  - In this paper we introduce the overlapping design consensus for the construction
      of models in design and the related value judgments. The overlapping design
      consensus is inspired by Rawls' overlapping consensus. The overlapping design
      consensus is a well-informed, mutual agreement among all stakeholders based on
      fairness. Fairness is respected if all stakeholders' interests are given due and
      equal attention. For reaching such fair agreement, we apply Rawls' original
      position and reflective equilibrium to modeling. We argue that by striving for
      the original position, stakeholders expel invalid arguments, hierarchies,
      unwarranted beliefs, and bargaining effects from influencing the consensus. The
      reflective equilibrium requires that stakeholders' beliefs cohere with the final
      agreement and its justification. Therefore, the overlapping design consensus is
      not only an agreement to decisions, as most other stakeholder approaches, it is
      also an agreement to their justification and that this justification is
      consistent with each stakeholders' beliefs. For supporting fairness, we argue
      that fairness qualifies as a maxim in modeling. We furthermore distinguish values
      embedded in a model from values that are implied by its context of application.
      Finally, we conclude that for reaching an overlapping design consensus
      communication about properties of and values related to a model is required.

PMID- 25051871
TI  - Introduction: The progress of science.

PMID- 25051872
TI  - Pure science and the problem of progress.
AB  - How should we understand scientific progress? Kuhn famously discussed science as
      its own internally driven venture, structured by paradigms. He also famously had
      a problem describing progress in science, as problem-solving ability failed to
      provide a clear rubric across paradigm change--paradigm changes tossed out
      problems as well as solving them. I argue here that much of Kuhn's inability to
      articulate a clear view of scientific progress stems from his focus on pure
      science and a neglect of applied science. I trace the history of the distinction
      between pure and applied science, showing how the distinction came about, the
      rhetorical uses to which the distinction has been put, and how pure science came
      to be both more valued by scientists and philosophers. I argue that the
      distinction between pure and applied science does not stand up to philosophical
      scrutiny, and that once we relinquish it, we can provide Kuhn with a clear sense
      of scientific progress. It is not one, though, that will ultimately prove
      acceptable. For that, societal evaluations of scientific work are needed.

PMID- 25051873
TI  - Empirical progress and nomic truth approximation revisited.
AB  - In my From Instrumentalism to Constructive Realism (2000) I have shown how an
      instrumentalist account of empirical progress can be related to nomic truth
      approximation. However, it was assumed that a strong notion of nomic theories was
      needed for that analysis. In this paper it is shown, in terms of truth and
      falsity content, that the analysis already applies when, in line with scientific
      common sense, nomic theories are merely assumed to exclude certain conceptual
      possibilities as nomic possibilities.

PMID- 25051874
TI  - Scientific progress as increasing verisimilitude.
AB  - According to the foundationalist picture, shared by many rationalists and
      positivist empiricists, science makes cognitive progress by accumulating
      justified truths. Fallibilists, who point out that complete certainty cannot be
      achieved in empirical science, can still argue that even successions of false
      theories may progress toward the truth. This proposal was supported by Karl
      Popper with his notion of truthlikeness or verisimilitude. Popper's own technical
      definition failed, but the idea that scientific progress means increasing
      truthlikeness can be expressed by defining degrees of truthlikeness in terms of
      similarities between states of affairs. This paper defends the verisimilitude
      approach against Alexander Bird who argues that the "semantic" definition (in
      terms of truth or truthlikeness alone) is not sufficient to define progress, but
      the "epistemic" definition referring to justification and knowledge is more
      adequate. Here Bird ignores the crucial distinction between real progress and
      estimated progress, explicated by the difference between absolute (and usually
      unknown) degrees of truthlikeness and their evidence-relative expected values.
      Further, it is argued that Bird's idea of returning to the cumulative model of
      growth requires an implausible trick of transforming past false theories into
      true ones.

PMID- 25051875
TI  - Kuhn's Structure of Scientific Revolutions between sociology and epistemology.
AB  - The aim of the paper is to clarify Kuhn's theory of scientific revolutions. We
      propose to discriminate between a scientific revolution, which is a sociological
      event of a change of attitude of the scientific community with respect to a
      particular theory, and an epistemic rupture, which is a linguistic fact
      consisting of a discontinuity in the linguistic framework in which this theory is
      formulated. We propose a classification of epistemic ruptures into four types. In
      the paper, each of these types of epistemic ruptures is illustrated by examples
      from physics. The classification of epistemic ruptures can be used as a basis for
      a classification of scientific revolutions and thus for a refinement of our view
      of the progress of science.

PMID- 25051876
TI  - A revolution without tooth and claw-redefining the physical base units.
AB  - A case study is presented of a recent proposal by the major metrology institutes
      to redefine four of the physical base units, namely kilogram, ampere, mole, and
      kelvin. The episode shows a number of features that are unusual for progress in
      an objective science: for example, the progress is not triggered by experimental
      discoveries or theoretical innovations; also, the new definitions are eventually
      implemented by means of a voting process. In the philosophical analysis, I will
      first argue that the episode provides considerable evidence for confirmation
      holism, i.e. the claim that central statements in fundamental science cannot be
      tested in isolation; second, that the episode satisfies many of the criteria
      which Kuhn requires for scientific revolutions even though one would naturally
      classify it as normal science. These two observations are interrelated since
      holism can provide within normal science a possible source of future
      revolutionary periods.

PMID- 25051877
TI  - A comparison of two models of scientific progress.
AB  - Does science progress toward some goal or merely away from primitive beginnings?
      Two agent-based models are built to explain how possibly both kinds of
      progressive scientific change can result from the interactions of individuals
      exploring an epistemic landscape. These models are shown to result in
      qualitatively different predictions about what the resulting system of science
      should be like.

PMID- 25051878
TI  - The future stewards of the profession.

PMID- 25051879
TI  - Parents' perspectives on transition and postsecondary outcomes for their children
      who are d/Deaf or hard of hearing.
AB  - Parent involvement and parent expectations are important factors in successful
      academic and career outcomes for students who are d/Deaf or hard of hearing.
      Parental roles are particularly important during the transition planning process
      for students with disabilities. Results are presented from an exploratory study
      of 56 parents that measured their involvement, perceptions, and expectations
      during the transition process. Parents positively rated their experiences with
      the individualized education program (IEP) process and held high expectations for
      both their child's educational attainment and employment. However, differences in
      expectations and perceptions emerged among parents whose children had co
      occurring disabilities. Future directions for research and practice are
      discussed, including the implications of the demographics of the study sample and
      the relationship between parental demographics and parents' expectations for
      their children.

PMID- 25051880
TI  - Validating the Thinking Styles Inventory-Revised II among Chinese university
      students with hearing impairment through test accommodations.
AB  - The present study pioneered in adopting test accommodations to validate the
      Thinking Styles Inventory-Revised II (TSI-R2; Sternberg, Wagner, & Zhang, 2007)
      among Chinese university students with hearing impairment. A series of three
      studies were conducted that drew their samples from the same two universities, in
      which accommodating test directions (N = 213), combining test directions with
      language accommodations from students' perspectives (N = 366), and integrating
      test directions with language accommodations from teachers' perspectives (N =
      129) were used. The accommodated TSI-R2 generally indicated acceptable internal
      scale reliabilities and factorial validity for Chinese university students with
      hearing loss. Limitations in relation to the study participants are discussed, as
      well as test accommodations and the significance and implications of the study.

PMID- 25051881
TI  - Quantity processing in deaf and hard of hearing children: evidence from symbolic
      and nonsymbolic comparison tasks.
AB  - Deaf children usually achieve lower scores on numerical tasks than normally
      hearing peers. Explanations for mathematical disabilities in hearing children are
      based on quantity representation deficits (Geary, 1994) or on deficits in
      accessing these representations (Rousselle & Noel, 2008). The present study aimed
      to verify, by means of symbolic (Arabic digits) and nonsymbolic (dot
      constellations and hands) magnitude comparison tasks, whether deaf children show
      deficits in representations or in accessing numerical representations. The study
      participants were 10 prelocutive deaf children and 10 normally hearing children.
      Numerical distance and magnitude were manipulated. Response time (RT) analysis
      showed similar magnitude and distance effects in both groups on the 3 tasks.
      However, slower RTs were observed among the deaf participants on the symbolic
      task alone. These results suggest that although both groups' quantity
      representations were similar, the deaf group experienced a delay in accessing
      representations from symbolic codes.

PMID- 25051882
TI  - Explicitly teaching English through the air to students who are deaf or hard of
      hearing.
AB  - The effects of the Language for Learning curriculum (Engelmann & Osborne, 1999)
      on through-the-air (i.e., signed and/or spoken) English skills for students who
      are deaf or hard of hearing (DHH) were examined by means of a single-subject,
      concurrent-multiple-probes-across-participants design. Four 11-year-old
      participants varied in auditory access, IQ, and age at amplification and/or
      cochlear implantation. All students showed increased accuracy of through-the-air
      English skills after the intervention (i.e., 15-20 lessons) and maintained these
      skills when assessed 1 week and 1 month later. The findings yielded some
      promising results indicating that a Direct Instruction curriculum may be an
      efficacious way to teach morphology and syntax to DHH students.

PMID- 25051883
TI  - First steps in the journey from consumers to producers of research in deaf
      education.
AB  - Faculty shortages in the study of low-incidence sensory disabilities (deafness,
      blindness, deaf-blindness) constitute personnel preparation challenges, as
      documented by a variety of organizations. To alleviate this deficit in the low
      incidence sensory disability professoriat, the National Leadership Consortium for
      Sensory Disabilities (NLCSD) was created to support the preparation of preservice
      researchers in these disciplines. This qualitative study documents the emerging
      perceptions of research by deafness-focused NLCSD first-year doctoral Fellows
      during their participation in an online enrichment seminar. Thematic analysis of
      the online interactions of the Fellows reveals their initial steps in their
      journey from consumers to producers of research. Results of the study offer
      insight into the preparation process of leadership personnel in deaf education.

PMID- 25051884
TI  - Characterization of the MLO gene family in Rosaceae and gene expression analysis
      in Malus domestica.
AB  - BACKGROUND: Powdery mildew (PM) is a major fungal disease of thousands of plant
      species, including many cultivated Rosaceae. PM pathogenesis is associated with
      up-regulation of MLO genes during early stages of infection, causing down
      regulation of plant defense pathways. Specific members of the MLO gene family act
      as PM-susceptibility genes, as their loss-of-function mutations grant durable and
      broad-spectrum resistance. RESULTS: We carried out a genome-wide characterization
      of the MLO gene family in apple, peach and strawberry, and we isolated apricot
      MLO homologs through a PCR-approach. Evolutionary relationships between MLO
      homologs were studied and syntenic blocks constructed. Homologs that are
      candidates for being PM susceptibility genes were inferred by phylogenetic
      relationships with functionally characterized MLO genes and, in apple, by
      monitoring their expression following inoculation with the PM causal pathogen
      Podosphaera leucotricha. CONCLUSIONS: Genomic tools available for Rosaceae were
      exploited in order to characterize the MLO gene family. Candidate MLO
      susceptibility genes were identified. In follow-up studies it can be investigated
      whether silencing or a loss-of-function mutations in one or more of these
      candidate genes leads to PM resistance.

PMID- 25051885
TI  - Involvement of ERK1/2, p38 MAPK, and PI3K/Akt signaling pathways in the
      regulation of cell cycle progression by PTHrP in colon adenocarcinoma cells.
AB  - Parathyroid hormone-related peptide (PTHrP) is distributed in most fetal and
      adult tissues, and its expression correlates with the severity of colon
      carcinoma. Recently we obtained evidence that in Caco-2 cells, a cell line from
      human colorectal adenocarcinoma, exogenous PTHrP increases the number of live
      cells, via ERK1/2, p38 MAPK, and PI3-kinase and induces the expression of cyclin
      D1, a cell cycle regulatory protein. In this study, we further investigated the
      role of PTHrP in the regulation of the cell cycle progression in these intestinal
      cells. Flow cytometry analysis revealed that PTHrP treatment diminishes the
      number of cells in the G0/G1 phase and increases the number in both S and G2/M
      phases. The hormone increases the expression of CDK6 and diminishes the amount of
      negative cell cycle regulators p27Kip1, p15INK4B, and p53. However, PTHrP does
      not modify the expression of cyclin D3, CDK4, and p16INK4A. In addition,
      inhibitors of ERK1/2 (PD98059), p38 MAPK (SB203580), and PI3Kinase (LY294002)
      reversed PTHrP response in Caco-2 cells. Taken together, our results suggest that
      PTHrP positively modulates cell cycle progression and changes the expression of
      proteins involved in cell cycle regulation via ERK1/2, p38 MAPK, and PI3K
      signaling pathways in Caco-2 cells. 

PMID- 25051886
TI  - Correlation of lateral stenosis in MRI with symptoms, walking capacity and EMG
      findings in patients with surgically confirmed lateral lumbar spinal canal
      stenosis.
AB  - BACKGROUND: To evaluate the clinical significance of lateral lumbar spinal canal
      stenosis (LLSCS), found by magnetic resonance imaging (MRI), through correlating
      the imaging findings with patient symptoms, walking capacity and electromyography
      (EMG) measurements. METHOD: 102 patients with symptoms of LSS referred for
      operative treatment were studied in this uncontrolled study. Of these patients,
      subjects with distinct only lateral LSS were included. Accordingly, 140 roots in
      14 patients (mean age 58, range 48-76 years, male 43%) were evaluated. In MR
      images the entrance and mid zones of the lateral lumbar nerve root canal were
      graded as normal, narrowed but not compressed, or compressed. In quantitative
      analysis, the minimal widths of the lateral recess and mid zone area were
      measured. Clinical symptoms were recorded with the Oswestry Disability Index
      (ODI), overall Visual Analogue Scale (VAS), specific low back pain (LBP; NRS-11),
      specific leg pain (LP NRS-11), Beck Depression Inventory (BDI) and walking
      distance in the treadmill test. Lumbar paraspinal (L2- L5) and lower limb (L3 -
      S1) needle EMG studies were performed. The findings were classified root by root
      as 1 = normal, 2 = abnormal. The associations between radiological, EMG and
      clinical findings were tested with each other. RESULTS: EMG findings were normal
      in 92 roots and abnormal in 48 roots. All of the patients had at least one
      abnormal nerve root finding. Severity of the mid zone stenosis in MRI correlated
      with abnormal EMG findings (p = 0.015). Patients with abnormal EMG had also
      higher scores in the VAS (41.9 +/- 25.7 vs 31.5 +/- 18.1; p = 0.018), NRS leg
      pain (7.5 +/- 1.5 vs 6.3 +/- 2.1; p = 0.000) and BDI (9.8 +/- 3.8 vs 8.0 +/- 3.9;
      p = 0.014). However, no statistically significant correlations between MRI
      findings and clinical symptoms or walking capacity were found. CONCLUSIONS: Among
      persons previously selected for surgery, lateral stenosis seen on MRI correlates
      with EMG, and thus may be a clinically significant finding. Our EMG findings were
      also associated with patient symptoms. However, no relationships between the MRI
      findings and symptoms or walking capacity were found, suggesting their
      multifactorial etiology.

PMID- 25051887
TI  - 25-Hydroxyvitamin D and ankle-brachial blood pressure index in adults without
      peripheral artery disease.
AB  - BACKGROUND: Inverse association between lower level of 25-hydroxyvitamin D
      [25(OH)D] and higher prevalence of peripheral arterial disease (PAD) among
      individuals with cardiovascular diseases (CVD) is known. Less is known about the
      relationship between 25(OH)D and ankle-brachial blood pressure index (ABPI) in
      asymptomatic adults. We hypothesized a nonlinear relationship between 25(OH)D and
      ABPI in asymptomatic adults without PAD. METHODS: Data from the continuous NHANES
      (2001-2004) was used. Minimum of the two reported ABPI value was chosen for each
      individual (>18 years). Linear regression models with spline adjusted for
      demographic and traditional risk factors for CVD were used to examine nonlinear
      relationship between 25(OH)D and ABPI. Mean changes in ABPI per 10 ng/mL change
      in 25(OH)D were reported. RESULTS: Mean (SD) age and 25(OH)D levels of 4979
      participants (48% females) were 60.4 (13.22) years and 22.1 (8.68) ng/mL,
      respectively, while mean (SD) ABPI was 1.07 (0.15). We observed positive
      association between 25(OH)D and ABPI both in the univariable and multivariable
      regression models (all p < 0.05). In univariable regression with spline, a
      significant increase in ABPI (beta = 0.03, 95% CI: 0.02-0.04) was observed until
      25(OH)D reached but not above 27 ng/mL. Similarly, in multivariable spline
      models, 25(OH)D was positively associated with ABPI (beta = 0.02, 95% CI: 0.01
      0.03) only up to 27 ng/mL. CONCLUSIONS: In asymptomatic adults without PAD,
      rising serum 25(OH)D concentration but not above 27 ng/mL was associated with
      statistically significant increase in ABPI.

PMID- 25051888
TI  - Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical
      sensitivity in a chronic neuropathic pain model of spinal cord injury in rats.
AB  - Chronic neuropathic pain is a common consequence of spinal cord injury (SCI),
      develops over time and negatively impacts quality of life, often leading to
      substance abuse and suicide. Recent evidence has demonstrated that reactive
      oxygen species (ROS) play a role in contributing to neuropathic pain in SCI
      animal models. This investigation examines four compounds that reduce ROS and the
      downstream lipid peroxidation products, apocynin, 4-oxo-tempo, U-83836E, and
      tirilazad, and tests if these compounds can reduce nocioceptive behaviors in
      chronic SCI animals. Apocynin and 4-oxo-tempo significantly reduced abnormal
      mechanical hypersensitivity measured in forelimbs and hindlimbs in a model of
      chronic SCI-induced neuropathic pain. Thus, compounds that inhibit ROS or lipid
      peroxidation products can be used to ameliorate chronic neuropathic pain. We
      propose that the application of compounds that inhibit reactive oxygen species
      (ROS) and related downstream molecules will also reduce the behavioral measures
      of chronic neuropathic pain. Injury or trauma to nervous tissue leads to
      increased concentrations of ROS in the surviving tissue. Further damage from ROS
      molecules to dorsal lamina neurons leads to membrane excitability, the
      physiological correlate of chronic pain. Chronic pain is difficult to treat with
      current analgesics and this research will provide a novel therapy for this
      disease. 

PMID- 25051889
TI  - Historical overview of community health practitioners in Korea.
AB  - The Korean government introduced CHPs (Community Health Practitioners) as front
      line primary health care providers to address the health disparity between urban
      and rural areas. Through their dedicated contribution over last 30 years, the
      CHPs have improved Korea's public health through the successful control of high
      birth rates, a lowered maternal and infant mortality rate in the 1980s,
      eradication of parasitic infection, and containing many communicable diseases
      including hepatitis B. However, rapid changes in the health care environment and
      demands for health care among rural residents have required changes in the roles
      and functions of the CHPs. They are challenged by fundamental changes in the
      public health system addressing various health issues due to a rapidly aging
      society, pandemic of chronic disease, new infectious disease, and climate
      changes. CHPs should continuously transform their roles and functions to
      establish a lifelong health management system. This article presents a historical
      overview of the CHP system and their tasks and activities. Also, recent
      challenges that CHPs are facing and strategies to overcome those challenges will
      be discussed. This historical overview will be informative for other developing
      countries in resolving their own public health problems.

PMID- 25051890
TI  - Surface proteins of Staphylococcus aureus play an important role in experimental
      skin infection.
AB  - Staphylococcus aureus is the most common cause of skin infections that range from
      mild diseases up to life-threatening conditions. Mechanisms of S. aureus
      virulence in those infections remain poorly studied. To investigate the impact of
      S. aureus surface proteins on skin infection, we used mouse models of skin
      abscess formation and skin necrosis, induced by a subcutaneous injection of
      bacteria. In the skin abscess model, a sortase-deficient S. aureus strain lacking
      all of its cell-wall anchored proteins was less virulent than its wild-type
      strain. Also, strains specifically lacking protein A, fibronecting binding
      proteins, clumping factor A or surface protein SasF were impaired in their
      virulence. When a model of dermonecrosis was studied, the S. aureus surface
      proteins could not be shown to be involved. In summary, surface proteins play an
      important role in virulence of S. aureus skin abscess infections, but not in
      formation of skin necrosis.

PMID- 25051891
TI  - Special issue on molecular detection of trophic interactions: unpicking the
      tangled bank. Introduction.

PMID- 25051893
TI  - Continuity and change in children's longitudinal neural responses to numbers.
AB  - Human children possess the ability to approximate numerical quantity nonverbally
      from a young age. Over the course of early childhood, children develop
      increasingly precise representations of numerical values, including a symbolic
      number system that allows them to conceive of numerical information as Arabic
      numerals or number words. Functional brain imaging studies of adults report that
      activity in bilateral regions of the intraparietal sulcus (IPS) represents a key
      neural correlate of numerical cognition. Developmental neuroimaging studies
      indicate that the right IPS develops its number-related neural response profile
      more rapidly than the left IPS during early childhood. One prediction that can be
      derived from previous findings is that there is longitudinal continuity in the
      number-related neural responses of the right IPS over development while the
      development of the left IPS depends on the acquisition of numerical skills. We
      tested this hypothesis using fMRI in a longitudinal design with children ages 4
      to 9. We found that neural responses in the right IPS are correlated over a 1-2
      year period in young children whereas left IPS responses change systematically as
      a function of children's numerical discrimination acuity. The data are consistent
      with the hypothesis that functional properties of the right IPS in numerical
      processing are stable over early childhood whereas the functions of the left IPS
      are dynamically modulated by the development of numerical skills. 

PMID- 25051892
TI  - Blockade of CD40-TRAF2,3 or CD40-TRAF6 is sufficient to inhibit pro-inflammatory
      responses in non-haematopoietic cells.
AB  - Inhibition of the CD40-CD154 pathway controls inflammatory disorders.
      Unfortunately, administration of anti-CD154 monoclonal antibodies causes
      thromboembolism. Blockade of signalling downstream of CD40 may represent an
      approach to treat CD40-driven inflammatory disorders. Blocking tumour necrosis
      factor receptor-associated factor 6 (TRAF6) signalling downstream of CD40 in MHC
      II(+) cells diminishes inflammation. However, CD40-TRAF6 blockade may cause
      immunosuppression. We examined the role of CD40-TRAF2,3 and CD40-TRAF6 signalling
      in the development of pro-inflammatory responses in human non-haematopoietic and
      monocytic cells. Human aortic endothelial cells, aortic smooth muscle cells,
      renal proximal tubule epithelial cells, renal mesangial cells and monocytic cells
      were transduced with retroviral vectors that encode wild-type CD40, CD40 with a
      mutation that prevents TRAF2,3 recruitment (DeltaT2,3), TRAF6 recruitment
      (DeltaT6) or both TRAF2,3 plus TRAF6 recruitment (DeltaT2,3,6). Non
      haematopoietic cells that expressed CD40 DeltaT2,3 exhibited marked inhibition in
      CD154-induced up-regulation of vascular cell adhesion molecule 1, intercellular
      adhesion molecule 1 (ICAM-1), monocyte chemotactic protein 1 (MCP-1), tissue
      factor and matrix metalloproteinase 9. Similar results were obtained with cells
      that expressed CD40 DeltaT6. Although both mutations impaired ICAM-1 up
      regulation in monocytic cells, only expression of CD40 DeltaT6 reduced MCP-1 and
      tissue factor up-regulation in these cells. Treatment of endothelial and smooth
      muscle cells with cell-permeable peptides that block CD40-TRAF2,3 or CD40-TRAF6
      signalling impaired pro-inflammatory responses. In contrast, while the CD40
      TRAF2,3 blocking peptide did not reduce CD154-induced dendritic cell maturation,
      the CD40-TRAF6 blocking peptide impaired this response. Hence, preventing CD40
      TRAF2,3 or CD40-TRAF6 interaction inhibits pro-inflammatory responses in human
      non-haematopoietic cells. In contrast to inhibition of CD40-TRAF6 signalling,
      inhibition of CD40-TRAF2,3 signalling did not impair dendritic cell maturation.
      Blocking CD40-TRAF2,3 signalling may control CD40-CD154-dependent inflammatory
      disorders. 

PMID- 25051894
TI  - [Long-standing purpuric rash: Pityriasis lichenoides].

PMID- 25051895
TI  - [Post-traumatic high-flow priapism].

PMID- 25051896
TI  - Arsenite oxidation by a facultative chemolithoautotrophic Sinorhizobium sp. KGO-5
      isolated from arsenic-contaminated soil.
AB  - A chemolithoautotrophic arsenite-oxidizing bacterium, designated strain KGO-5,
      was isolated from arsenic-contaminated industrial soil. Strain KGO-5 was
      phylogenetically closely related with Sinorhizobium meliloti with 16S rRNA gene
      similarity of more than 99%, and oxidized 5 mM arsenite under autotrophic
      condition within 60 h with a doubling time of 3.0 h. Additions of 0.01-0.1% yeast
      extract enhanced the growth significantly, and the strain still oxidized arsenite
      efficiently with much lower doubling times of approximately 1.0 h. Arsenite
      oxidizing capacities (11.2-54.1 MUmol h(-1) mg dry cells(-1)) as well as arsenite
      oxidase (Aio) activities (1.76-10.0 mU mg protein(-1)) were found in the cells
      grown with arsenite, but neither could be detected in the cells grown without
      arsenite. Strain KGO-5 possessed putative aioA gene, which is closely related
      with AioA of Ensifer adhaerens. These results suggest that strain KGO-5 is a
      facultative chemolithoautotrophic arsenite oxidizer, and its Aio is induced by
      arsenic.

PMID- 25051897
TI  - Electives support autonomy and autonomous motivation in undergraduate medical
      education.

PMID- 25051899
TI  - Effect of an exclusion range of jaw movement data from the intercuspal positionon
      the estimation of the kinematic axis point.
AB  - In patients who have lost natural occlusal contacts, the centric relation is
      usually estimated based on several anatomical factors such as the
      temporomandibular joint and masticatory muscles except dental arch. The clinical
      procedure to record the centric relation often depends on the clinician's
      expertise and technique; an objective method to determine proper occlusal
      position is desirable. The kinematic axis point (KAP) is kinematically estimated
      from sagittal movements and is an ideal posterior reference point that is used in
      dental articulators for reproducing jaw movement. Occlusal registration using the
      KAP may serve as a definite objective technique. The aim of this study is to
      investigate the effect of the exclusion range of sagittal jaw movement data from
      the intercuspal position (ICP) on the estimation of the KAP. The complete and
      incomplete sagittal border movement data of dentate subjects were used to
      estimate the KAPs. The locations of the estimated KAPs were compared. The results
      indicate that the incomplete sagittal border jaw movement data set does not
      include data points inside a 7 mm distance from the ICP can be used for
      estimation of the KAP. In conclusion, the sagittal border jaw movement data
      around the ICP is not indispensable in the valid identification of the KAP.

PMID- 25051898
TI  - Expression of gamma-tocopherol methyltransferase in chloroplasts results in
      massive proliferation of the inner envelope membrane and decreases susceptibility
      to salt and metal-induced oxidative stresses by reducing reactive oxygen species.
AB  - The gamma-tocopherol methyltransferase (gamma-TMT) is an important enzyme
      regulating synthesis of four tocopherols (alpha, gamma, beta and delta). In this
      report, we investigated the role of gamma-TMT in regulating abiotic stress within
      chloroplasts. The At gamma-tmt overexpressed via the tobacco chloroplast genome
      accumulated up to 7.7% of the total leaf protein, resulting in massive
      proliferation of the inner envelope membrane (IEM, up to eight layers). Such high
      level expression of gamma-TMT converted most of gamma-tocopherol to alpha
      tocopherol in transplastomic seeds (~10-fold higher) in the absence of abiotic
      stress. When grown in 400 mm NaCl, alpha-tocopherol content in transplastomic TMT
      leaves increased up to 8.2-fold and 2.4-fold higher than wild-type leaves.
      Likewise, under heavy metal stress, alpha-tocopherol content in the TMT leaves
      increased up to 7.5-fold, twice higher than in the wild type. Under extreme salt
      stress, the wild type accumulated higher starch and total soluble sugars, but TMT
      plants were able to regulate sugar transport. Hydrogen peroxide and superoxide
      content in wild type increased up to 3-fold within 48 h of NaCl stress when
      compared to TMT plants. The ion leakage from TMT leaves was significantly less
      than wild-type plants under abiotic stress and with less malondialdehyde,
      indicating lower lipid peroxidation. Taken together, these studies show that
      alpha-tocopherol plays a crucial role in the alleviation of salt and heavy metal
      stresses by decreasing ROS, lipid peroxidation and ion leakage, in addition to
      enhancing vitamin E conversion. Increased proliferation of the IEM should
      facilitate studies on retrograde signalling from chloroplast to the nucleus. 

PMID- 25051900
TI  - Low torque levels can initiate a removal of the passivation layer and cause
      fretting in modular hip stems.
AB  - Taper connections of modular hip prostheses are at risk of fretting and
      corrosion, which can result in reduced implant survival. The purpose of this
      study was to identify the minimum torque required to initiate a removal of the
      passivation layer at the taper interface as a function of assembly force and
      axial load. Titanium stems and cobalt-chromium heads were assembled with peak
      impaction forces of 4.5 kN or 6.0 kN and then mounted on a materials testing
      machine whilst immersed in Ringer's solution. The stems were subjected to a
      static axial load (1 kN or 3 kN) along the taper axis. After a period of
      equilibration, a torque ramp from 0 to 15 Nm was manually applied and the
      galvanic potential was continuously recorded. Prostheses assembled with a force
      of 6 kN required a significantly higher torque to start a removal of the
      passivation layer compared to those assembled with 4.5 kN (7.23+/-0.55 Nm vs.
      3.92+/-0.97 Nm, p=0.029). No influence of the axial load on the fretting
      behaviour was found (p=0.486). The torque levels, which were demonstrated to
      initiate surface damage under either assembly force, can be readily reached
      during activities of daily living. The damage will be intensified in situations
      of large weight and high activity of the patient or malpositioning of the
      prosthesis.

PMID- 25051901
TI  - The phosphodiesterase 3 inhibitor cilostazol does not stimulate growth of
      colorectal liver metastases after major hepatectomy.
AB  - Liver failure after extended hepatectomy represents a major challenge in the
      surgery of hepatic colorectal metastasis. A previous study has indicated that
      inhibition of phosphodiesterase type 3 (PDE 3) stimulates liver regeneration.
      However, little is known whether PDE 3 inhibitors, such as cilostazol, also
      stimulate the growth of remnant metastases. Therefore, we herein studied the
      effect of cilostazol on engraftment, vascularization and growth of colorectal
      liver metastasis after major hepatectomy. WAG-rats underwent either major
      hepatectomy or sham operation. Metastases were induced by subcapsular
      implantation of 5 * 10(5) CC531-colorectal cancer cells. Animals were daily
      treated with cilostazol (5 mg/kg body weight) or glucose solution. Tumor growth
      was measured by high-resolution ultrasound at days 7 and 14. Tumor
      vascularization and tumor cell proliferation were determined by
      immunohistochemistry and western blotting. High-resolution ultrasound analysis in
      hepatectomized and non-hepatectomized animals showed that cilostazol does not
      stimulate tumor growth. Accordingly, the number of PCNA-positive tumor cells did
      not differ between cilostazol-treated animals and sham-treated controls.
      Interestingly, cilostazol reduced tumor vascularization in both hepatectomized
      and non-hepatectomized animals. This was indicated by a significantly lower
      number of platelet-endothelial cell adhesion molecule (PECAM-1)-positive cells in
      tumors of cilostazol-treated animals compared to sham-treated controls. The PDE 3
      inhibitor cilostazol does not stimulate the growth of colorectal metastases
      during liver regeneration after major hepatectomy.

PMID- 25051902
TI  - Fluticasone propionate/formoterol: a fixed-combination therapy with flexible
      dosage.
AB  - International guidelines describe asthma control as the main outcome of asthma
      management. Prevention of symptoms, improved quality of life, and reduction of
      exacerbations are the main components, consequently decreasing health care costs.
      However, many of these objectives remain unmet in real life: several surveys show
      that a large proportion of asthmatic patients are not well controlled despite the
      efficacy of current available treatment. Several randomized controlled clinical
      trials indicate that combining inhaled corticosteroids and long-acting beta2
      agonists, by means of a single inhaler, greatly improves the management of the
      disease. The results of 9 multicenter phase III clinical studies demonstrate that
      the fixed combination of fluticasone propionate/formoterol in a single inhaler is
      effective in terms of lung function and symptom control. These studies highlight
      the dose flexibility, safety and tolerability of this new inhaled combination.
      These characteristics meet the recommendations of international guidelines, and
      the preferences of respiratory physicians who identified these aspects as
      critical components of a successful asthma therapy. Combination of fluticasone
      propionate/formoterol in a single inhaler provides potent anti-inflammatory
      activity of fluticasone propionate and rapid onset of action of the beta2-agonist
      formoterol making this association a viable treatment option both in terms of
      effectiveness and compliance. 

PMID- 25051904
TI  - Atypical Femoral Fractures: A Teaching Perspective.
AB  - This article provides an overview of atypical femoral fractures with a highlight
      on their radiographic findings. Potent antiresorptive agents such as
      bisphosphonates or denosumab have been associated with the development of such
      fractures. However, at this time, a causal association has not been conclusively
      established. Atypical femoral fractures are insufficiency fractures, which
      frequently present with bone pain. Early identification of characteristic
      radiographic features and withdrawal of antiresorptive therapy may prevent the
      development of completed atypical femoral fractures. 

PMID- 25051905
TI  - Advance distribution of misoprostol for the prevention of postpartum hemorrhage
      in South Sudan.
AB  - OBJECTIVE: To determine if high uterotonic coverage can be achieved in South
      Sudan through a facility- and community-focused postpartum hemorrhage (PPH)
      prevention program. METHODS: The program was implemented from October 2012 to
      March 2013. At health facilities, active management of the third stage of labor
      (AMTSL) was emphasized. During prenatal care and home visits, misoprostol was
      distributed to pregnant women at approximately 32 weeks of pregnancy for the
      prevention of PPH at home births. Data on uterotonic coverage and other program
      outcomes were collected through facility registers, home visits, and postpartum
      interviews. RESULTS: In total, 533 home births and 394 facility-based births were
      reported. Misoprostol was distributed in advance to 787 (84.9%) pregnant women,
      of whom 652 (82.8%) received the drug during home visits. Among the women who
      delivered at home, 527 (98.9%) reported taking misoprostol. A uterotonic for PPH
      prevention was provided at 342 (86.8%) facility-based deliveries. Total
      uterotonic coverage was 93.7%. No adverse events were reported. CONCLUSION: It is
      feasible to achieve high coverage of uterotonic use in a low-resource and
      postconflict setting with few skilled birth attendants through a combination of
      advance misoprostol distribution and AMTSL at facilities. Advance distribution
      through home visits was key to achieving high coverage of misoprostol use.

PMID- 25051906
TI  - Infectious diseases consultations at an Australian tertiary hospital: a review of
      11,511 inpatient consultations.
AB  - BACKGROUND: Infectious diseases (ID) clinicians provide an important service
      within tertiary hospitals. However, as a largely consultation-based service,
      their value can be difficult to evaluate. AIMS: A review of 13.5 years of
      consultations was undertaken to define the scope of the service and any changes
      over time. METHODS: ID consultations at the Princess Alexandra Hospital are
      tracked on a database, recording information including the requesting team,
      indication for and outcome of the consult. Incident formal inpatient
      consultations between July 1999 and December 2012 were reviewed retrospectively.
      Phone consultations, repeat consultations and ID admissions were excluded.
      RESULTS: Eleven thousand five hundred and eleven consultations were identified,
      with annual consultations increasing significantly during this period. Overall,
      formal consultations were performed on 1.3% of admissions. Consultations were
      most commonly requested by orthopaedics (14.3%) and general medicine (11.4%). The
      two most common syndromes triggering a consult were bloodstream infection (13.9%)
      and complicated soft tissue infection (7.8%). The final diagnosis was most
      frequently osteomyelitis (7.9%). Staphylococcus aureus (19.4%) and Pseudomonas
      aeruginosa (8.3%) were the most commonly identified pathogens. CONCLUSION: The
      demand for ID consultations has increased over time and there are likely to be
      many drivers of this increase. Information derived from this audit can enhance
      the ID service by guiding service delivery, trainee education and informing
      funding or accreditation applications.

PMID- 25051907
TI  - Preventing excessive weight gain during pregnancy and promoting postpartum weight
      loss: a pilot lifestyle intervention for overweight and obese African American
      women.
AB  - To test the feasibility and acceptability of a theory-based lifestyle
      intervention designed to prevent excessive weight gain during pregnancy and
      promote weight loss in the early postpartum period in overweight and obese
      African American women. Sixteen pregnant women (<=18 weeks gestation) were
      recruited from prenatal clinics in Columbia, South Carolina in 2011 and assigned
      to a lifestyle intervention program. The intervention, guided by formative
      research, consisted of an individual counseling session followed by eight group
      sessions alternated with telephone counseling contacts that continued through 36
      weeks of gestation. At 6-8 weeks postpartum, participants received a home visit
      and up to three counseling calls through week 12. Medical charts were reviewed
      for 38 contemporary controls who met the same inclusion criteria and attended the
      same prenatal clinics. Compared to controls, study participants gained less total
      weight, had a smaller weekly rate of weight gain across the 2nd and 3rd
      trimesters (0.89 vs. 0.96 lbs), and were less likely to exceed weight gain
      recommendations (56.3 vs. 65.8 %). At 12 weeks postpartum, study participants
      retained 2.6 lbs from their prepregnancy weight, half of study participants were
      at their prepregnancy weight or lower, and only 35 % retained >=5 lbs. The
      intervention also demonstrated success in promoting physical activity and
      reducing caloric intake, and was well-received by participants. The initial
      results were promising. The lessons learned can help inform future studies. The
      efficacy of our intervention will be tested in a large randomized controlled
      trial. 

PMID- 25051908
TI  - Bone loss in patients with posterior gleno-humeral instability: a systematic
      review.
AB  - PURPOSE: The aim of this systematic review was to analyse outcomes of surgical
      procedures for glenoid and/or humeral bony defects, performed singularly or in
      combination, in patients with posterior gleno-humeral instability. A secondary
      aim was to establish in clinical settings which percentage of glenoid or humeral
      bone loss should be treated with a bony procedure to avoid recurrence of
      dislocation. METHODS: A systematic review of the literature according to the
      PRISMA guidelines was performed. A comprehensive search of PubMed, Medline,
      CINAHL, Cochrane, Embase, Ovid, and Google Scholar databases was performed using
      various combinations of the keywords "shoulder", "posterior instability",
      "dislocation", "bone loss", "reversed bony Bankart", "osseous glenoid defects",
      "glenoid bone grafting", "glenoid", "humeral head", "surgery", "gleno-humeral",
      "reversed Hill-Sachs", over the years 1966-2014. Data were independently
      extracted by all the investigators: demographics, previous surgery, imaging
      assessment, bone defect measurement, diagnosis, surgical management, return to
      sport, complications, and outcome measurements. The outcome parameters were
      recurrence of dislocation and clinical scores. RESULTS: Nineteen articles,
      describing patients with glenoid bony defects, humeral bony defects, or both in
      the setting of posterior gleno-humeral instability were included. A total of 328
      shoulders in 321 patients were included, with a median age at surgery of 33.4
      years, ranging from 14 to 79 years. Patients were assessed at a median follow-up
      period of 3.6 years (ranging from 8 months to 22 years). A redislocation event
      occurred in 32 (10 %) shoulders. The redislocation event occurred in 2 (10 %) of
      20 shoulders with glenoid bony defect and in 12 (11 %) of 114 shoulders with
      humeral bony defect. CONCLUSION: Even though the general principle of treating
      recognized glenoid and humeral bone defects in patients with posterior gleno
      humeral instability is widely accepted, to date few studies in the literature
      accurately establish which bone defects should be treated with bony procedures
      and the exact correlation between percentage of bone loss and higher risk of
      redislocation in clinical settings. A limitation to the present systematic review
      is the small number of included patients, due to the rare entity of posterior
      bone defects/reversed Hill-Sachs. The clinical relevance is that the results of
      this systematic review can be helpful to guide clinicians in the management of
      patients with posterior gleno-humeral instability and glenoid and/or humeral bony
      defects. This manuscript also highlights the need for accurate description of
      results in further investigations. The main drawback of the available articles in
      the topic is that they rarely clarify the percentage of bone loss in patients
      undergoing a redislocation event. LEVEL OF EVIDENCE: IV.

PMID- 25051909
TI  - Functional rehabilitation of patients with acute Achilles tendon rupture: a meta
      analysis of current evidence.
AB  - PURPOSE: The optimal treatment for acute Achilles tendon rupture (ATR) is
      continuously debated. Recent studies have proposed that the choice of either
      operative or non-operative treatment may not be as important as rehabilitation,
      suggesting that functional rehabilitation should be preferred over traditional
      immobilization. The purpose of this meta-analysis of randomized controlled trials
      (RCTs) was to compare functional rehabilitation to immobilization in the
      treatment of ATR. METHOD: This meta-analysis was conducted using the databases:
      PubMed, EMBASE, Rehabilitation and Sports Medicine Source, AMED, CINAHL, Cochrane
      Library and PEDro using the search terms: "Achilles tendon," "rupture,"
      "mobilization" and "immobilization". Seven RCTs involving 427 participants were
      eligible for inclusion, with a total of 211 participants treated with functional
      rehabilitation and 216 treated with immobilization. RESULTS: Re-rupture rate,
      other complications, strength, range of motion, duration of sick leave, return to
      sport and patient satisfaction were examined. There were no statistically
      significant differences between groups. A trend favoring functional
      rehabilitation was seen regarding the examined outcomes. CONCLUSION: Functional
      rehabilitation after acute Achilles tendon rupture does not increase the rate of
      re-rupture or other complications. A trend toward earlier return to work and
      sport, and increased patient satisfaction was found when functional
      rehabilitation was used. The present literature is of low-to-average quality, and
      the basic constructs of the examined treatment and study protocols vary
      considerably. Larger, randomized controlled trials using validated outcome
      measures are needed to confirm the findings. LEVEL OF EVIDENCE: II.

PMID- 25051903
TI  - Gender-differences in disease distribution and outcome in hospitalized elderly:
      data from the REPOSI study.
AB  - BACKGROUND AND PURPOSE: Women live longer and outnumber men. On the other hand,
      older women develop more chronic diseases and conditions such as arthritis,
      osteoporosis and depression, leading to a greater number of years of living with
      disabilities. The aim of this study was to describe whether or not there are
      gender differences in the demographic profile, disease distribution and outcome
      in a population of hospitalized elderly people. METHODS: Retrospective
      observational study including all patients recruited for the REPOSI study in the
      year 2010. Analyses are referred to the whole group and gender categorization was
      applied. RESULTS: A total of 1380 hospitalized elderly subjects, 50.5% women and
      49.5% men, were considered. Women were older than men, more often widow and
      living alone or in nursing homes. Disease distribution showed that malignancy,
      diabetes, coronary artery disease, chronic kidney disease and chronic obstructive
      pulmonary disease were more frequent in men, but hypertension, osteoarthritis,
      anemia and depression were more frequent in women. Severity and comorbidity
      indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were
      higher in men, while cognitive impairment evaluated by the Short Blessed Test
      (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in
      daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3
      month mortality rates were higher in men. CONCLUSIONS: Our study showed a gender
      dimorphism in the demographic and morbidity profiles of hospitalized elderly
      people, emphasizing once more the need for a personalized process of healthcare.

PMID- 25051910
TI  - Complications involving the extensor mechanism after total knee arthroplasty.
AB  - PURPOSE: To overview the complications involving extensor apparatus of the knee
      following total knee arthroplasty (TKA) and to summarize which are the lines of
      treatment available and their reported outcomes in literature. METHODS: A
      comprehensive search of several databases was performed using as basic keywords
      "complications after TKA", "extensor mechanism disruption", "periprosthetic
      patellar fracture", "quadriceps tendon rupture", "quadriceps tendon rupture"
      isolated or combined with other terms by using Boolean operators. The
      methodological quality of each article was also evaluated using the Coleman
      methodology score (CMS). RESULTS: Twenty-nine studies were evaluated. The mean
      CMS of the studies selected was 33.1/100. Patellar fractures, requiring surgical
      treatment when there is rupture of the extensor mechanism or loosening of the
      patellar component, were treated surgically in 28.1 % of patients. The patellar
      and quadriceps tendon ruptures were surgically treated with reconstruction or
      augmented repair, respectively, in 98.6 and 76.5 %. CONCLUSION: Complications
      involving the extensor apparatus of the knee following a TKA need early and
      appropriate management to avoid their devastating influence on joint
      functionality. Management has to be evaluated very carefully based on the site of
      the lesion, integrity of the prosthetic components and surrounding tissue to
      restore, and the patients' individual characteristics. The surgical approach for
      comminuted periprosthetic fractures and reconstruction of torn tendons of the
      extensor apparatus are needed to restore function and decrease pain, but, given
      the poor methodological quality of the studies published so far, it is not clear
      which surgical technique or graft leads to better outcomes. Therefore, there is
      an absolute need for better designed comparative trials producing clearer and
      stronger evidence on this critical matter. LEVEL OF EVIDENCE: IV.

PMID- 25051911
TI  - Simulation of the optimal femoral insertion site in medial patellofemoral
      ligament reconstruction.
AB  - PURPOSE: To develop and validate a new simulation system to predict the optimal
      femoral insertion site of the medial patellofemoral ligament (MPFL) using
      preprogrammed conditions of graft length change. METHODS: A computed tomography
      scan was performed for constructing bone surface models of the patella and the
      femur. Lateral radiographs of the knee and axial radiographs of the
      patellofemoral joint at knee flexion were used for constructing a three
      dimensional patellofemoral joint model by 3D-2D image matching at each knee
      flexion angle. To determine the optimal femoral insertion site, the following
      three conditions were devised: (1) MPFL behaves isometric from 0 degrees  to 60
      degrees , (2) MPFL is most taut at full extension, and (3) MPFL is slack at more
      than 60 degrees  of knee flexion. Every condition was applied to the femoral bone
      surface model, and the area that fulfilled all three conditions was defined as
      the optimal femoral insertion site of MPFL. Twenty knees of ten healthy
      volunteers were assessed to verify the simulation. Comparison between simulated
      optimal femoral insertion and anatomical insertion was done. RESULTS: The mean
      simulated optimal femoral insertion was close to the anatomical insertion site.
      There were no significant differences in the proximal-distal position and
      anterior-posterior position between the simulated insertion and the anatomical
      insertion sites. CONCLUSION: The system can be useful for predicting the optimal
      femoral insertion site as a part of a preoperative plan for MPFL reconstruction,
      and it may help surgeons to determine the optimal femoral insertion site during
      MPFL reconstruction.

PMID- 25051913
TI  - Serum albumin as a significant prognostic factor in patients with malignant
      pleural mesothelioma.
AB  - Our aim was to evaluate the prognostic role of the pretreatment serum albumin
      level in patients with malignant pleural mesothelioma (MPM) receiving platinum
      based systemic chemotherapy. From 1995 to 2013, a total of 97 patients receiving
      platinum-based systemic chemotherapy for newly diagnosed MPM were enrolled. All
      clinical information and laboratory results were retrospectively collected from
      the medical records. The Kaplan-Meier method was used to calculate survival. The
      Cox proportional hazards model was used to identify significant independent
      prognostic factors for predicting survival. In total, 34 of the 97 patients (35.1
      %) had hypoalbuminaemia (albumin <= 35 g/l). The 1-year overall survival rate was
      44.1 % for patients with hypoalbuminaemia and 72.0 % for patients with a normal
      albumin level. Multivariate analysis indicated that pretreatment albumin was an
      independent prognostic factor in MPM. Patients with hypoalbuminaemia had a
      greater risk of death than those with a normal albumin level [hazard ratio (HR)
      1.778; 95 % confidence interval (CI) 1.504-2.998; P = 0.031]. When albumin was
      entered as a continuous variable in the Cox regression model, the HR of death was
      significantly decreased by 9.8 % (95 % CI 0.851-0.956) for each 1-g/l increment.
      The pretreatment serum albumin level is a simple, inexpensive and easily
      measurable marker with prognostic significance in MPM patients treated with
      platinum-based systemic chemotherapy.

PMID- 25051914
TI  - Evaluating the expression and diagnostic value of human epididymis protein 4
      (HE4) in small cell lung cancer.
AB  - We evaluated the expression and diagnostic value of human epididymis protein 4
      (HE4) in small cell lung cancer (SCLC). Serum HE4 level was measured in serum
      samples from 30 healthy controls and 49 patients with SCLC using enzyme-linked
      immunosorbent assay. HE4 expression in tumor tissues was analyzed by
      immunohistochemical staining. The results show that serum HE4 level is
      significantly higher in SCLC patients than those in healthy controls, which is
      also the case in tumor tissues where strong intracytoplasmic staining is
      demonstrable. Using the optimal cutoff value of 84.19 pmol/l, serum HE4 level
      distinguishes SCLC patients from healthy controls with a sensitivity of 69.4 %, a
      specificity of 93.3 %, and the area under the receiver operating characteristic
      curve (AUC) of 0.85. Compared to other well-known tumor markers used in lung
      cancer diagnosis, HE4 shows the highest sensitivity (69.4 %, 34 of 49) and
      accuracy (78.5 %, 62 of 79) in diagnosing SCLC, and combinations with other tumor
      markers further increase the sensitivity and accuracy. These findings suggest
      that HE4 levels are greatly elevated in sera and tumor tissues of patients with
      SCLC and serum HE4 is a potential diagnostic marker for patients with SCLC.

PMID- 25051912
TI  - Focus on genetic and epigenetic events of colorectal cancer pathogenesis:
      implications for molecular diagnosis.
AB  - Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep
      process that involved accumulation of tumor suppressor genes and oncogenes
      mutations, such as APC, TP53 and KRAS. However, this assumption proposed a
      relatively limited repertoire of genetic alterations. In the last decade, there
      have been major advances in knowledge of multiple molecular pathways involved in
      CRC pathogenesis, particularly regarding cytogenetic and epigenetic events.
      Microsatellite instability, chromosomal instability and CpG island methylator
      phenotype are the most analyzed cytogenetic changes, while DNA methylation,
      modifications in histone proteins and microRNAs (miRNAs) were analyzed in the
      field of epigenetic alterations. Therefore, CRC development results from
      interactions at many levels between genetic and epigenetic amendments.
      Furthermore, hereditary cancer syndrome and individual or environmental risk
      factors should not be ignored. The difficulties in this setting are addressed to
      understand the molecular basis of individual susceptibility to CRC and to
      determine the roles of genetic and epigenetic alterations, in order to yield more
      effective prevention strategies in CRC patients and directing their treatment.
      This review summarizes the most investigated biomolecular pathways involved in
      CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their
      possible use to stratify susceptible patients into appropriate screening or
      surveillance programs. 

PMID- 25051915
TI  - EphB4 regulates the growth and migration of pancreatic cancer cells.
AB  - Pancreatic cancer is a serious threat to human life. Moreover, its treatment is
      complicated and its prognosis is very poor. Therefore, a new method for the
      diagnosis and treatment of pancreatic cancer is very essential. In this study, a
      eukaryotic expression plasmid targeting EphB4 was constructed and transfected
      into PANC-1 pancreatic cancer cells to investigate the inhibition of cell growth
      and the progression of iRNA against EphB4. This study provides the basis for the
      gene therapy of pancreatic cancer. The recombinant eukaryotic EphB4 expression
      plasmid, pSIREN-RetroQ-ZsGreen-EphB4 and a negative control plasmid, pSIREN
      RetroQ-ZsGreen-N, were constructed. At 48 h after transfection, the relative
      messenger RNA (mRNA) and protein levels of EphB4 were measured by RT-PCR and
      western blot. The proliferation of the transfected cells was determined using the
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while cell
      migration ability was analyzed using the scratch migration assay. At 48 h after
      transient transfection, EphB4 mRNA expression was significantly decreased in
      transfected PANC-1 cells as compared to the control group (P < 0.01). In vitro,
      inhibition of EphB4 expression weakened the proliferation and cell migration
      ability of PANC-1 cells compared to the control group. The small interfering RNA
      (siRNA) eukaryotic expression plasmid vector targeting EphB4 was successfully
      constructed and effectively transfected into PANC-1 cells. The recombinant
      plasmid can inhibit the expression of EphB4 mRNA and protein in PANC-1 cells, as
      well as cell growth and migration.

PMID- 25051916
TI  - N-acetyltransferase 2 status and gastric cancer risk: a meta-analysis.
AB  - Case-control studies on the association between N-acetyltransferase 2 (NAT2)
      genotype and gastric cancer have provided either controversial or inconclusive
      results. In order to clarify the influence of NAT2 acetylation status on gastric
      cancer risk, a meta-analysis was undertaken. The primary outcome measure was the
      odds ratio (OR) for the risk of gastric cancer associated with the NAT2 genotype.
      The overall result showed that there was no statistically significant association
      between NAT2 status and gastric cancer risk (slow acetylation vs. rapid
      acetylation, OR = 1.10, 95 % confidence interval (CI) 0.97-1.25, p = 0.12). In
      the analysis stratified by East Asian ethnicity, a significant association was
      found between gastric cancer and the NAT2 genotype (slow acetylation vs. rapid
      acetylation, OR = 1.33, 95 % CI 1.11-1.59, p = 0.002). Our pooled data suggest
      that the NAT2 acetylation status has an effect on the risk of gastric cancer
      among East Asian populations.

PMID- 25051917
TI  - Correlations of IFN-gamma genetic polymorphisms with susceptibility to breast
      cancer: a meta-analysis.
AB  - The meta-analysis was conducted to evaluate the correlations between common
      genetic polymorphisms in the IFN-gamma gene and susceptibility to breast cancer.
      The following electronic databases were searched without language restrictions:
      MEDLINE (1966 ~ 2013), the Cochrane Library Database (issue 12, 2013), EMBASE
      (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the
      Chinese Biomedical Database (CBM) (1982 ~ 2013). Meta-analysis was performed with
      the use of the STATA statistical software. Odds ratios (OR) with their 95 %
      confidence intervals (95 % CIs) were calculated. Nine clinical case-control
      studies met all the inclusion criteria and were included in this meta-analysis. A
      total of 1,182 breast cancer patients and 1,525 healthy controls were involved in
      this meta-analysis. Three functional polymorphisms were assessed, including
      rs2069705 C>T, rs2430561 T>A, and CA repeats 2/X. Our meta-analysis results
      indicated that IFN-gamma genetic polymorphisms might be significantly associated
      with an increased risk of breast cancer (allele model: OR = 1.37, 95 % CI = 1.03
      ~ 1.83, P = 0.031; dominant model: OR = 1.55, 95 % CI = 1.01 ~ 2.37, P = 0.046;
      homozygous model: OR = 2.23, 95 % CI = 1.30 ~ 3.82, P = 0.004; respectively),
      especially the rs2430561 T>A polymorphism. Subgroup analysis based on ethnicity
      suggested that genetic polymorphisms in the IFN-gamma gene were closely
      correlated with increased breast cancer risk among Asians (allele model: OR =
      1.21, 95 % CI = 1.02 ~ 1.58, P = 0.017; dominant model: OR = 3.44, 95 % CI = 2.07
      ~ 5.71, P < 0.001; recessive model: OR = 1.58, 95 % CI = 1.06 ~ 2.37, P = 0.025;
      homozygous model: OR = 1.83, 95 % CI = 1.19 ~ 2.80, P = 0.006; respectively), but
      not among Caucasians (all P > 0.05). Our meta-analysis supported the hypothesis
      that IFN-gamma genetic polymorphisms may contribute to an increased risk of
      breast cancer, especially the rs2430561 T>A polymorphism among Asians.

PMID- 25051918
TI  - Acetabular cartilage segmentation in CT arthrography based on a bone-normalized
      probabilistic atlas.
AB  - PURPOSE: Determination of acetabular cartilage loss in the hip joint is a
      clinically significant metric that requires image segmentation. A new
      semiautomatic method to segment acetabular cartilage in computed tomography (CT)
      arthrography scans was developed and tested. METHODS: A semiautomatic
      segmentation method was developed based on the combination of anatomical and
      statistical information. Anatomical information is identified using the pelvic
      bone position and the contact area between cartilage and bone. Statistical
      information is acquired from CT intensity modeling of acetabular cartilage and
      adjacent tissue structures. This method was applied to the identification of
      acetabular cartilages in 37 intra-articular CT arthrography scans. RESULTS: The
      semiautomatic anatomical-statistical method performed better than other
      segmentation methods. The semiautomatic method was effective in noisy scans and
      was able to detect damaged cartilage. CONCLUSIONS: The new semiautomatic method
      segments acetabular cartilage by fully utilizing the statistical and anatomical
      information in CT arthrography datasets. This method for hip joint cartilage
      segmentation has potential for use in many clinical applications.

PMID- 25051920
TI  - Engineering beta-lactamase zymogens for use in protease activity assays.
AB  - In this study, the concept of autoinhibition, a mechanism of protein activity
      regulation, was applied to the design and engineering of a beta-lactamase
      zymogen. Using this zymogen, a sensitive protease assay method was developed in
      which activation of the zymogen by proteases produces an amplified absorbance
      signal. The approach reported here can be adapted for engineering of zymogens as
      biological sensors and components of synthetic signaling pathways. 

PMID- 25051919
TI  - Colonisation resistance in the sand fly gut: Leishmania protects Lutzomyia
      longipalpis from bacterial infection.
AB  - BACKGROUND: Phlebotomine sand flies transmit the haemoflagellate Leishmania, the
      causative agent of human leishmaniasis. The Leishmania promastigotes are confined
      to the gut lumen and are exposed to the gut microbiota within female sand flies.
      Here we study the colonisation resistance of yeast and bacteria in preventing the
      establishment of a Leishmania population in sand flies and the ability of
      Leishmania to provide colonisation resistance towards the insect bacterial
      pathogen Serratia marcescens that is also pathogenic towards Leishmania. METHODS:
      We isolated microorganisms from wild-caught and laboratory-reared female
      Lutzomyia longipalpis, identified as Pseudozyma sp. Asaia sp. and Ochrobactrum
      intermedium. We fed the females with a sugar meal containing the microorganisms
      and then subsequently fed them with a bloodmeal containing Leishmania mexicana
      and recorded the development of the Leishmania population. Further experiments
      examined the effect of first colonising the sand fly gut with L. mexicana
      followed by feeding with, Serratia marcescens, an insect bacterial pathogen. The
      mortality of the flies due to S. marcescens was recorded in the presence and
      absence of Leishmania. RESULTS: There was a reduction in the number of flies
      harbouring a Leishmania population that had been pre-fed with Pseudozyma sp. and
      Asaia sp. or O. intermedium. Experiments in which L. mexicana colonised the sand
      fly gut prior to being fed an insect bacterial pathogen, Serratia marcescens,
      showed that the survival of flies with a Leishmania infection was significantly
      higher compared to flies without Leishmania infection. CONCLUSIONS: The yeast and
      bacterial colonisation experiments show that the presence of sand fly gut
      microorganisms reduce the potential for Leishmania to establish within the sand
      fly vector. Sand flies infected with Leishmania were able to survive an attack by
      the bacterial pathogen that would have killed the insect and we concluded that
      Leishmania may benefit its insect host whilst increasing the potential to
      establish itself in the sand fly vector. We suggest that the increased ability of
      the sand fly to withstand a bacterial entomopathogen, due to the presence of the
      Leishmania, may provide an evolutionary pressure for the maintenance of the
      Leishmania-vector association.

PMID- 25051922
TI  - Immunological tools: engaging students in the use and analysis of flow cytometry
      and enzyme-linked immunosorbent assay (ELISA).
AB  - Flow cytometry and enzyme-linked immunosorbent assay (ELISA) are commonly used
      techniques associated with clinical and research applications within the
      immunology and medical fields. The use of these techniques is becoming
      increasingly valuable in many life science and engineering disciplines as well.
      Herein, we report the development and evaluation of a novel half-semester course
      that focused on introducing undergraduate and graduate students to advance
      conceptual and technical skills associated with flow cytometry and ELISA, with
      emphasis on applications, experimental design, and data analysis. This course was
      offered in the North Carolina State University Biotechnology Program over three
      semesters and consisted of weekly lectures and laboratories. Students performed
      and/or analyzed flow cytometry and ELISA in three separate laboratory exercises:
      (1) identification of transgenic zebrafish hematopoietic cells, (2) analysis of
      transfection efficiency, and (3) analysis of cytokine production upon
      lipopolysaccharide stimulation. Student learning outcomes were achieved as
      demonstrated by multiple means of assessment, including three laboratory reports,
      a data analysis laboratory practicum, and a cumulative final exam. Further,
      anonymous student self-assessment revealed increased student confidence in the
      knowledge and skill sets defined in the learning outcomes.

PMID- 25051923
TI  - Temperature-dependent bursting pattern analysis by modified Plant model.
AB  - Many electrophysiological properties of neuron including firing rates and
      rhythmical oscillation change in response to a temperature variation, but the
      mechanism underlying these correlations remains unverified. In this study, we
      analyzed various action potential (AP) parameters of bursting pacemaker neurons
      in the abdominal ganglion of Aplysia juliana to examine whether or not bursting
      patterns are altered in response to temperature change. Here we found that the
      inter-burst interval, burst duration, and number of spike during burst decreased
      as temperature increased. On the other hand, the numbers of bursts per minute and
      numbers of spikes per minute increased and then decreased, but interspike
      interval during burst firstly decreased and then increased. We also tested the
      reproducibility of temperature-dependent changes in bursting patterns and AP
      parameters. Finally we performed computational simulations of these phenomena by
      using a modified Plant model composed of equations with temperature-dependent
      scaling factors to mathematically clarify the temperature-dependent changes of
      bursting patterns in burst-firing neurons. Taken together, we found that the
      modified Plant model could trace the ionic mechanism underlying the temperature
      dependent change in bursting pattern from experiments with bursting pacemaker
      neurons in the abdominal ganglia of Aplysia juliana. 

PMID- 25051924
TI  - Development of a strontium chronic effects benchmark for aquatic life in
      freshwater.
AB  - There are no national water-quality guidelines for strontium for the protection
      of freshwater aquatic life in North America or elsewhere. Available data on the
      acute and chronic toxicity of strontium to freshwater aquatic life were compiled
      and reviewed. Acute toxicity was reported to occur at concentrations ranging from
      75 mg/L to 15 000 mg/L. The majority of chronic effects occurred at
      concentrations above 11 mg/L; however, calculation of a representative benchmark
      was confounded by results from 4 studies indicating that chronic effects occurred
      at lower concentrations than all other studies, in 2 cases below background
      concentrations reported for US and European streams. Two of these studies,
      including 1 reporting effects below background concentrations, were repeated and
      found not to be reproducible; chronic effects occurred at considerably higher
      strontium concentrations than in the original studies. Studies with narrow
      mouthed toad and goldfish were not repeated; both studies reported chronic
      effects below background concentrations, and both studies had been conducted by
      the authors of 1 of the 2 studies that were repeated and shown to be
      nonreproducible. Studies by these authors (3 of the 4 confounding studies),
      conducted over 30 yr ago, lacked detail in reporting of methods and results. It
      is thus likely that repeating the toad and goldfish studies would also have
      resulted in a higher strontium effects concentration. A strontium chronic effects
      benchmark of 10.7 mg/L that incorporates the results of additional testing
      summarized in the present study is proposed for freshwater environments.

PMID- 25051925
TI  - Interventions for strabismic amblyopia.
AB  - BACKGROUND: Amblyopia is reduced visual acuity in one or both eyes in the absence
      of any demonstrable abnormality of the visual pathway. It is not immediately
      resolved by the correction of refractive error. Strabismus develops in
      approximately 5% to 8% of the general population. The aim of treatment for
      amblyopia is to obtain the best possible level of vision in the amblyopic eye.
      Different treatment options were examined within the review. OBJECTIVES: By
      reviewing the available evidence we wanted to establish the most effective
      treatment for strabismic amblyopia. In particular this review aimed to examine
      the impact of conventional occlusion therapy for strabismic amblyopia and to
      analyse the role of partial occlusion and optical penalisation for strabismic
      amblyopia. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes
      and Vision Group Trials Register) (2013, Issue 12), Ovid MEDLINE, Ovid MEDLINE In
      Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE
      (January 1946 to January 2014), EMBASE (January 1980 to January 2014), Latin
      American and Caribbean Health Sciences Literature Database (LILACS) (January 1982
      to January 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled
      trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health
      Organization (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 30 January 2014. SELECTION CRITERIA: We included randomised controlled trials
      (RCTs) for the treatment of strabismic amblyopia including participants of any
      age. DATA COLLECTION AND ANALYSIS: Two authors working independently extracted
      and entered data into Review Manager 5 and then independently checked the data
      for errors. MAIN RESULTS: We included three RCTs in this review. The studies
      reported mean logMAR visual acuity achieved. Mean difference in visual acuity was
      calculated. When comparing conventional part-time occlusion (with any necessary
      glasses), PEDIG 2006 reported that this treatment was more beneficial than
      glasses alone for strabismic amblyopia; the mean difference between groups was 
      0.18 LogMAR (statistically significant 95% confidence interval (CI) -0.32 to 
      0.04). Supplementing occlusion therapy with near activities may produce a better
      visual outcome compared to non-near activities after four weeks of treatment
      (PEDIG 2005). The results of the pilot study showed mean difference between
      groups was -0.17 LogMAR (95% CI -0.53 to 0.19). Results from a larger RCT (PEDIG
      2008) are now available, showing that supplementing occlusion therapy with near
      activities may produce a better visual outcome after eight weeks of treatment;
      the mean difference between groups was -0.02 LogMAR (95% CI -0.10 to 0.06). One
      further article ia awaiting assessment as in its current format there is
      insufficient information to include (Alotaibi 2012). AUTHORS' CONCLUSIONS:
      Occlusion, whilst wearing necessary refractive correction, appears to be more
      effective than refractive correction alone in the treatment of strabismic
      amblyopia. The benefit of combining near activities with occlusion is unproven.
      No RCTs were found that assessed the role of either partial occlusion or optical
      penalisation to refractive correction for strabismic amblyopia.

PMID- 25051926
TI  - [Venereal diseases - a long way to go].

PMID- 25051928
TI  - [Drug-induced acute interstitial nephritis].

PMID- 25051930
TI  - Prevalence and determinants of sexually transmitted infections in women at risk
      undergoing abortion in a Swiss primary care setting.
AB  - BACKGROUND: Specific prevalence data are needed to assess the burden of sexually
      transmitted infections (STIs) in specific settings where data are scant, such as
      women seeking early termination of pregnancy (TOP). We aimed to investigate the
      prevalence of STIs and its determinants in women at risk (e. g. pathological
      cervical swab) undergoing TOP in a primary care setting in Switzerland. METHODS:
      Cross-sectional study of 620 women seeking abortion counselling at a general
      practice in Zurich, Switzerland. Patients' characteristics were assessed and in
      case of pathological cervical swab a PCR-based screening for Chlamydia
      trachomatis (CT), Mycoplasma genitalium (MG) and Neisseria gonorrhoeae (NG) was
      initiated to estimate STI prevalence. Bi-and multivariable analysis were used to
      investigate STI determinants. RESULTS: 585 out of the 620 women presenting for
      counselling resulted in TOP. 581 (93,7%) cervical specimens were available with
      272 having pathological signs (46,8%), thus were considered at risk for STIs. In
      192 screened samples 28 STIs (14,6%) (95% CI: 10,3-20,3%) were detected,
      predominantly CT (17 cases) followed by MG (9 cases) and NG (2 cases). Compared
      to non-immigrants, immigrants were more likely to have a STI (adjusted OR 2,63;
      p=0,037) Non-screened women were significantly more often self-payers (31,3%)
      compared to screened women (8,3%) (p<0,001). CONCLUSION: We found a high STI
      prevalence in women presenting for TOP in a Swiss primary care setting. Women
      with a migration background seemed to be a vulnerable subgroup. Public health
      efforts are needed to implement cost-effective screening and case management
      programmes in this population at risk for STIs.

PMID- 25051931
TI  - [Robot-assisted and computer-based neurorehabilitation for children: the story
      behind].
AB  - Impairments of the central motor system can either be congenital (e. g. cerebral
      palsy) or acquired (e. g. traumatic brain injury, stroke). These lesions are the
      most frequent morbidities necessitating neuro-rehabilitative measures in
      childhood. Robot-assisted rehabilitation in combination with virtual reality can
      complement conventional therapies and provide a task-specific training, with a
      high number of repetitions over a prolonged time period. The advantage of virtual
      reality is that it can provide a real time feedback about the patient's
      performance. Furthermore, challenging virtual scenarios especially motivate young
      patients to continue with otherwise monotonous exercises. Preliminary findings
      indicate that robot-assisted training in children with central motor impairment
      could be beneficial, but conclusive evidence about its efficacy is still missing.

PMID- 25051932
TI  - [Why does our heart fibrillate?- or what goats can teach us].
AB  - Our present knowledge about cardiac electrophysiology is based on numerous
      experiments and discoveries going back to the Greek antique and ancient Egypt.
      Exploration of cardiac anatomy was followed by the description of circulation and
      cardiac physiology in the 17th century. In the early 20th century cardiac
      electrophysiology became the new field of interest and was studied with the help
      of numerous animal experiments (squid, rays, dogs, goats, mice and other
      species). We ought to be grateful for the knowledge and possibilities in modern
      medicine that were made possible by the great number of researchers, patients and
      animals that contributed to this. 

PMID- 25051933
TI  - [Harmless bruises? Coagulopathy despite normal INR].
AB  - Acquired hemophilia is a rare but severe bleeding disorder caused by
      autoantibodies mostly against factor VIII. Clinically it mostly presents with
      soft tissue and muscular bleeding. Diagnostics include a prolonged aPTT,
      antibodies against FVIII and a reduced FVIII titre. Acute bleeding is controlled
      with recombinant factor VIIa (NovoSeven((r))) or activated prothrombin complex
      (FEIBA((r))), as both bypass FVIII in the coagulation pathway. Treatment to
      reduce the inhibitor consists of immunosuppression with corticosteroids,
      cyclophosphamid and can be extended with rituximab.

PMID- 25051934
TI  - [Subdural hematoma in elderly patients].

PMID- 25051935
TI  - [Hydrocolloid in diabetic foot ulcers: better than current dressings?].

PMID- 25051936
TI  - [Prostatectomy vs. "watchful waiting" in early prostate cancer].

PMID- 25051937
TI  - [Aspirin does not prevent myocardial infarcts in and after non-cardiac
      operations].

PMID- 25051941
TI  - [Personalities in medical history. Ruggero Oddi].

PMID- 25051942
TI  - Yellow-light generation and engineering in zinc-doped cadmium sulfide nanobelts
      with low-threshold two-photon excitation.
AB  - Through a simple doping route with zinc ion as a dopant in cadmium sulfide
      nanobelts, a bright yellow-colored light was obtained. The detailed chromaticity
      and brightness of the light can be engineered by the dopant concentration and the
      pumping power, which are used to control the dominant wavelength to any fine
      yellow color, and even cover the sodium-yellow-line of 589 nm. The nanobelts were
      synthesized through a chemical vapor deposition method. The peak shift of the XRD
      result proves that the zinc ions as a dopant exist in the nanobelts rather than
      in the ZnCdS alloy formation. Time-resolved photoluminescence of the nanobelt
      reveals the existence of the defect-related state, which induces a red band to
      further mix with green band-edge emission to form the yellow light. Moreover, low
      threshold two-photon excitation was observed in the proper Zn-doped cadmium
      sulfide nanobelts. The dopant and pumping power-tuned generation and engineering
      of the yellow light makes it possible to use this kind of material as yellow
      light-emitting source. 

PMID- 25051943
TI  - Predictors of medication-related problems among medicaid patients participating
      in a pharmacist-provided telephonic medication therapy management program.
AB  - STUDY OBJECTIVE: To identify predictors of medication-related problems (MRPs)
      among Medicaid patients participating in a telephonic medication therapy
      management (MTM) program. DESIGN: Retrospective analysis of data from patients
      enrolled in a previously published study. DATA SOURCES: Two Medicaid
      administrative claims file databases (for health care utilization and
      prescription dispensing information) and one pharmacy organization file for MTM
      program information. PATIENTS: Seven hundred twelve adult Medicaid patients who
      participated in a statewide pharmacist-provided telephone-based MTM program and
      who received an initial medication therapy review. MEASUREMENTS AND MAIN RESULTS:
      The primary dependent variable was the number of MRPs detected during the initial
      medication therapy review. Secondary dependent variables were the detection of
      one or more MRPs related to indication, effectiveness, safety, and adherence.
      Predictor variables were selected a priori that, from the literature and our own
      practice experiences, were hypothesized as being potentially associated with
      MRPs: demographics, comorbidities, medication use, and health care utilization.
      Bivariate analyses were performed, and multivariable models were constructed. All
      predictor variables with significant associations (defined a priori as p<0.1)
      with the median number of MRPs detected were then entered into a three-block
      multiple linear regression model. The overall model was significant (p<0.001,
      R(2)  = 0.064). Significant predictors of any MRPs (p<0.05) were total number of
      medications, obesity, dyslipidemia, and one or more emergency department visits
      in the past 3 months. For indication-related MRPs, the model was significant
      (p<0.001, R(2)  = 0.049), and predictors included female sex, obesity,
      dyslipidemia, and total number of medications (p<0.05). For effectiveness-related
      MRPs, the model was significant (p<0.001, R(2)  = 0.054), and predictors included
      bone disease and dyslipidemia (p<0.05). For safety-related MRPs, the model was
      significant (p<0.001, R(2)  = 0.046), and dyslipidemia was a predictor (p<0.05).
      No significant predictors of adherence-related MRPs were identified. CONCLUSION:
      This analysis supports the relative importance of number of medications as a
      predictor of MRPs in the Medicaid population and identifies other predictors.
      However, given the models' low R(2) values, these findings indicate that other
      unknown factors are clearly important and that criteria commonly used for
      determining MTM eligibility may be inadequate in identifying appropriate patients
      for MTM in a Medicaid population.

PMID- 25051944
TI  - Redefining diastolic dysfunction grading: combination of E/A <=0.75 and
      deceleration time >140 ms and E/epsilon' >=10.
AB  - OBJECTIVES: This study sought to examine left atrial (LA) mechanics and the
      prognostic impact of patients with echocardiographic findings of E/A ratio
      <=0.75, deceleration time (DcT) of mitral E-wave >140 ms, but E/epsilon' >=10.
      BACKGROUND: Traditional diastolic dysfunction (DD) grading system could not
      classify every patient into a specific group. We considered the group of patients
      with E/A <=0.75, DcT >140 ms, but E/epsilon' >=10 (proposed new DD grade) as a
      new group in the DD grading system. METHODS: A total of 1,362 consecutive
      patients were stratified according to the new DD grading system, and the LA
      volumes, strain, and strain rates were measured by 2-dimensional speckle-tracking
      analysis. All patients were followed up to determine cardiac death and major
      adverse cardiac events. RESULTS: An E/A <=0.75, DcT >140 ms, but E/epsilon' >=10
      was observed in 227 patients (17%). LA volumes in patients with the new DD grade
      were between those of the impaired relaxation group and the pseudonormal group.
      LA strain of the new DD grade was similar to that of the pseudonormal group,
      whereas LA booster function was preserved as in the impaired relaxation group.
      During a mean follow-up of 3.0 +/- 1.1 years, 25 patients had cardiac death and
      61 had major adverse cardiac events. Event-free survival for major adverse
      cardiac events of the new DD grade was worse than that of the impaired relaxation
      group but similar to that of the pseudonormal group. CONCLUSIONS: The new DD
      grade is frequently observed and has a prognosis similar to that of the
      pseudonormal group but significantly worse than that of the impaired relaxation
      group. However, LA booster function was maintained at the expense of LA volume
      enlargement. Thus, the new grade should be a distinct entity for routine DD
      grading.

PMID- 25051946
TI  - Long-term outcomes of neointimal hyperplasia without neoatherosclerosis after
      drug-eluting stent implantation.
AB  - OBJECTIVES: The aim of this study was to investigate the correlation between in
      stent neointimal tissue without features of neoatherosclerosis and long-term
      clinical outcomes. BACKGROUND: Recent studies have reported differential
      morphological characteristics of in-stent neointimal tissue assessed by optical
      coherence tomography (OCT). METHODS: The study population consisted of 336
      patients with 368 drug-eluting stent-treated lesions. Patients received a follow
      up OCT examination without any intervention. OCT-based neointima was categorized
      as homogeneous (n = 227 lesions in 208 patients), heterogeneous (n = 79 lesions
      in 73 patients), or layered (n = 62 lesions in 55 patients). Major adverse
      cardiac events (MACE) (a composite of cardiac death, nonfatal myocardial
      infarction, or target lesion revascularization) were assessed according to
      neointimal patterns during long-term clinical follow-up after OCT examination.
      RESULTS: The time interval between stent implantation and OCT examination was
      similar among the 3 groups (p = 0.64). On multivariate logistic regression
      analysis, the significant determinant for the heterogeneous neointima was age
      (odds ratio [OR]: 1.037, 95% confidence interval [CI]: 1.007 to 1.068, p = 0.015)
      and an initial clinical presentation of acute coronary syndrome (OR: 1.967, 95%
      CI: 1.159 to 3.339, p = 0.012). The overall median follow-up duration for all
      patients after follow-up OCT examination was 31.0 months, and this was
      statistically different among the heterogeneous group (22.0 months), the
      homogeneous group (34.0 months), and the layered group (28.0 months, overall p =
      0.002). MACE occurred more frequently in patients with heterogeneous neointima
      over a median 31-month follow-up period after OCT examination (13.7% vs. 2.9% in
      homogeneous vs. 7.3% in layered, p = 0.001). A propensity score-adjusted Cox
      regression analysis showed that independent risk factors for MACE were inclusion
      in the heterogeneous neointima (hazard ratio: 3.925, 95% CI: 1.445 to 10.662, p =
      0.007) and minimal lumen cross-sectional area (hazard ratio: 0.368, 95% CI: 0.242
      to 0.560, p < 0.001). CONCLUSIONS: Determination of neointimal characteristics is
      helpful in predicting long-term clinical outcomes. Our data suggest that
      heterogeneous lesions are linked to poor long-term clinical prognoses.

PMID- 25051945
TI  - Coronary vessel wall contrast enhancement imaging as a potential direct marker of
      coronary involvement: integration of findings from CAD and SLE patients.
AB  - OBJECTIVES: This study investigated the feasibility of visual and quantitative
      assessment of coronary vessel wall contrast enhancement (CE) for detection of
      symptomatic atherosclerotic coronary artery disease (CAD) and subclinical
      coronary vasculitis in autoimmune inflammatory disease (systemic lupus
      erythematosus [SLE]), as well as the association with aortic stiffness, an
      established marker of risk. BACKGROUND: Coronary CE by cardiac magnetic resonance
      (CMR) is a novel noninvasive approach to visualize gadolinium contrast uptake
      within the coronary artery vessel wall. METHODS: A total of 75 subjects (CAD: n =
      25; SLE: n = 27; control: n = 23) underwent CMR imaging using a 3-T clinical
      scanner. Coronary arteries were visualized by a T2-prepared steady state free
      precession technique. Coronary wall CE was visualized using inversion-recovery T1
      weighted gradient echo sequence 40 min after administration of 0.2 mmol/kg
      gadobutrol. Proximal coronary segments were visually examined for distribution of
      CE and quantified for contrast-to-noise ratio (CNR) and total CE area. RESULTS:
      Coronary CE was prevalent in patients (93%, n = 42) with a diffuse pattern for
      SLE and a patchy/regional distribution in CAD patients. Compared with control
      subjects, CNR values and total CE area in patients with CAD and SLE were
      significantly higher (mean CNR: 3.9 +/- 2.5 vs. 6.9 +/- 2.5 vs. 6.8 +/- 2.0,
      respectively; p < 0.001; total CE area: median 0.8 [interquartile range (IQR):
      0.6 to 1.2] vs. 3.2 [IQR: 2.6 to 4.0] vs. 3.3 [IQR: 1.9 to 4.5], respectively; p
      < 0.001). Both measures were positively associated with aortic stiffness (CNR: r
      = 0.61, p < 0.01; total CE area: 0.36, p = 0.03), hypercholesterolemia (r = 0.68,
      p < 0.001; r = 0.61, p < 0.001) and hypertension (r = 0.40, p < 0.01; r = 0.32, p
      < 0.05). CONCLUSIONS: We demonstrate that quantification of coronary CE by CNR
      and total CE area is feasible for detection of subclinical and clinical uptake of
      gadolinium within the coronary vessel wall. Coronary vessel wall CE may become an
      instrumental novel direct marker of vessel wall injury and remodeling in
      subpopulations at risk.

PMID- 25051947
TI  - CMR-based identification of critical isthmus sites of ischemic and nonischemic
      ventricular tachycardia.
AB  - OBJECTIVES: This study evaluates whether contrast-enhanced (CE) cardiac magnetic
      resonance (CMR) can be used to identify critical isthmus sites for ventricular
      tachycardia (VT) in ischemic and nonischemic heart disease. BACKGROUND: Fibrosis
      interspersed with viable myocytes may cause re-entrant VT. CE-CMR has the ability
      to accurately delineate fibrosis. METHODS: Patients who underwent VT ablation
      with CE-CMR integration were included. After the procedure, critical isthmus
      sites (defined as sites with a >=11 of 12 pacemap, concealed entrainment, or VT
      termination during ablation) were projected on CMR-derived 3-dimensional (3D)
      scar reconstructions. The scar transmurality and signal intensity at all critical
      isthmus, central isthmus, and exit sites were compared to the average of the
      entire scar. The distance to >75% transmural scar and to the core-border zone
      (BZ) transition was calculated. The area within 5 mm of both >75% transmural scar
      and the core-BZ transition was calculated. RESULTS: In 44 patients (23 ischemic
      and 21 nonischemic, left ventricular ejection fraction 44 +/- 12%), a total of
      110 VTs were induced (cycle length 290 +/- 67 ms). Critical isthmus sites were
      identified for 78 VTs (71%) based on >=11 of 12 pacemaps (67 VTs), concealed
      entrainment (10 VTs), and/or termination (30 VTs). The critical isthmus sites,
      and in particular central isthmus sites, had high scar transmurality and signal
      intensity compared with the average of the entire scar. Of the pacemap, concealed
      entrainment, and termination sites, 74%, 100%, and 84% were within 5 mm of >75%
      transmural scar, and 67%, 100%, and 94% were within 5 mm of the core-BZ
      transition, respectively. The areas within 5 mm of both >75% transmural scar and
      the core-BZ transition (median 13% of LV) contained all concealed entrainment
      sites and 77% of termination sites. CONCLUSIONS: Both in ischemic and nonischemic
      VT, critical isthmus sites are typically located in close proximity to the CMR
      derived core-BZ transition and to >75% transmural scar. These findings suggest
      that CMR-derived scar characteristics may guide to critical isthmus sites during
      VT ablation.

PMID- 25051948
TI  - Carotid intima-media thickness and plaque in cardiovascular risk assessment.
AB  - Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular
      (CV) risk in multiple large studies. Careful evaluation of CIMT studies reveals
      discrepancies in the comprehensiveness with which CIMT is assessed-the number of
      carotid segments evaluated (common carotid artery [CCA], internal carotid artery
      [ICA], or the carotid bulb), the type of measurements made (mean or maximum of
      single measurements, mean of the mean, or mean of the maximum for multiple
      measurements), the number of imaging angles used, whether plaques were included
      in the intima-media thickness (IMT) measurement, the report of adjusted or
      unadjusted models, risk association versus risk prediction, and the arbitrary
      cutoff points for CIMT and for plaque to predict risk. Measuring the far wall of
      the CCA was shown to be the least variable method for assessing IMT. However,
      meta-analyses suggest that CCA-IMT alone only minimally improves predictive power
      beyond traditional risk factors, whereas inclusion of the carotid bulb and ICA
      IMT improves prediction of both cardiac risk and stroke risk. Carotid plaque
      appears to be a more powerful predictor of CV risk compared with CIMT alone.
      Quantitative measures of plaques such as plaque number, plaque thickness, plaque
      area, and 3-dimensional assessment of plaque volume appear to be progressively
      more sensitive in predicting CV risk than mere assessment of plaque presence.
      Limited data show that plaque characteristics including plaque vascularity may
      improve CV disease risk stratification further. IMT measurement at the CCA,
      carotid bulb, and ICA that allows inclusion of plaque in the IMT measurement or
      CCA-IMT measurement along with plaque assessment in all carotid segments is
      emerging as the focus of carotid artery ultrasound imaging for CV risk
      prediction. 

PMID- 25051949
TI  - Chemopreventive and anti-leukemic effects of ethanol extracts of Moringa oleifera
      leaves on wistar rats bearing benzene induced leukemia.
AB  - Pharmacological exploitation of natural compounds has continued to lead to
      development of non-synthetic and non-toxic anticancer agents that are promising
      at ameliorating the menace of neoplastic diseases such as leukemia. This study is
      an attempt to determine the chemopreventive and antileukemic activities of
      ethanol extracts of Moringa oleifera leaves on benzene induced leukemia bearing
      rats. Leukemia was induced by intravenous injection of 0.2 mL benzene solution 48
      hourly for 4 weeks in appropriate rat groups. Ethanol extract of Moringa oleifera
      (EMO) leaves was administered at 0.2 mL of 100 mg/mL to respective treatment rat
      groups. A standard antileukemic drug (cyclophosphamide) was also used to treat
      appropriate rat groups. Clinical examination of liver and spleen with
      hematological parameters were employed to assess the leukemia burden following
      analysis of the rat blood samples on Sysmex KX-21N automated instrument. Leukemia
      induction reflected in severe anemia and a marked leukocytosis over the
      control/baseline group. Liver and spleen enlargements were also observed in group
      exposed to benzene carcinogen. The in vivo antioxidative potential of EMO was
      evaluated using Malondialdehyde (MDA) and reduced glutathione (GSH) levels. The
      liver MDA and GSH levels obtained in benzene induced leukemic rats treated with
      EMO compared favorably with those obtained in similar treatments with the
      standard drug (p< 0.05). The extract demonstrated chemopreventive and anti
      leukemic activities as much as the standard anti-leukemic drug (p>0.05) by
      ameliorating the induced leukemic condition in the affected rat groups owing to
      its bioactive constituents. This study reveals that the extract might be an
      active, natural and non-toxic anticancer drug lead. 

PMID- 25051950
TI  - A Retrospective Study on the Incidence of Seizures among Neurosurgical Patients
      Who Treated with Imipenem/Cilastatin or Meropenem.
AB  - OBJECTIVE: We sought to evaluate the safety of imipenem and meropenem in the
      treatment of infections in neurosurgical patients. METHODS: An observational
      retrospective study was conducted of consecutive cases treated with imipenem from
      Sept. 2007 to Sept. 2009 and meropenem within 1 year from Sept. 2008 in Beijing
      Tiantan Hospital, China. Data including the dosage and duration of the drug use,
      occurrence of seizures and mortality outcome was collected from the electronic
      pharmacy records. The incidence of epilepsy, epileptic standardized morbidity
      rate (SMR) were reported. Attention was paid to the relationship between the use
      of imipenem/meropenem and the incidence of epilepsy. RESULTS: The imipenem
      patients within two years amounted to 71, with mean age 45.9+/-20.2 years, male
      to female ratio 46/25. The incidence of epilepsy was 11.3% (8 cases). Among them,
      1 case occurred during treatment (1/633, 1.6/1000 patient-days), and the
      remaining 7 cases occurred before treatment (7/2819, 2.5/1000 patient-days), with
      the standardized incidence rate 0.64, 95% CI (0.08-5.18).The meropenem patients
      within one year amounted to 92, mean age 45.1+/-19.4 years, male to female ratio
      51/41. The incidence of epilepsy was 6.5% (6 cases). 2 occurred during treatment
      (2/582, 2.0/1000 patients-hospital days) and 4 before treatment (4/2047, 3.4/1000
      patients-inpatient days), standardized incidence rate 1.76, 95% CI (0.32-9.63).
      CONCLUSION: Despite many other epileptogenic factors, imipenem or meropenem did
      not increase the risk of seizures in neurosurgical patients. There was not
      further risk for patients with pre-existing seizures or creatinine clearance
      abnormalities when dosed appropriate.

PMID- 25051951
TI  - Aortic valve adaptation to aortic root dilatation: insights into the mechanism of
      functional aortic regurgitation from 3-dimensional cardiac computed tomography.
AB  - BACKGROUND: The 3-dimensional relationship between aortic root and cusp is
      essential to understand the mechanism of aortic regurgitation (AR) because of
      aortic root dilatation (ARD). We sought to test the hypothesis that the stretched
      cusps in ARD enlarge to compensate for ARD. METHODS AND RESULTS: Computed
      tomography imaged 92 patients (57 with ARD, 29 with moderate to severe AR, 28
      without significant AR) and 35 normal controls. Specialized 3-dimensional
      software measured individual cusp surface areas relative to maximal mid-sinus
      cross-sectional area and minimal 3-dimensional annular area, coaptation area
      fraction, and asymmetry of sinus volumes and intercommissural distances. Total
      open cusp surface area increased (P<0.001) from 7.6+/-1.4 cm(2)/m(2) in normals
      to 12.9+/-2.2 cm(2)/m(2) in AR-negative and 15.2+/-3.3 cm(2)/m(2) in AR-positive
      patients. However, the ratio of closed cusp surface area to maximal mid-sinus
      area, reflecting cusp adaptation, decreased from normals to AR-negative to AR
      positive patients (1.38+/-0.20, 1.15+/-0.15, 0.88+/-0.15; P<0.001), creating the
      lowest coaptation area fraction. Cusp distensibility (closed diastolic versus
      open area) decreased from 20% in controls and AR-negative patients to 5% in AR
      positive patients (P<0.001). Multivariate determinants of AR and coaptation area
      fraction reflected both sinus size and cusp-to-annular adaptation. ARD was also
      progressively asymmetrical with root size, and individual cusp surface areas
      failed to match this asymmetry. CONCLUSIONS: Aortic cusp enlargement occurs in
      ARD, but cusp adaptation and distensibility become limited in prominent,
      asymmetrical ARD, leading to AR. Optimal AR repair tailored to individual patient
      anatomy can benefit from appreciating valve adaptation and 3-dimensional
      relationships; understanding cusp adaptation mechanisms may ultimately provide
      therapeutic opportunities to improve such compensation.

PMID- 25051952
TI  - Estimation of vascular endothelial growth factor gene -460 C/T polymorphism as a
      biomarker in oral squamous cell carcinoma patients from the Indian subcontinent.
AB  - AIM: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies
      in India. Vascular endothelial growth factor (VEGF), a major mediator of
      angiogenesis, is known to play a key role in the pathophysiology of
      tumorigenesis. Polymorphisms of the VEGF gene have been shown to influence the
      risk of OSCC, but it remains to be elucidated in the Indian population. Thus, the
      present study was designed to detect the VEGF gene -460 C/T polymorphism in OSCC
      patients from the Indian population, which is genetically distinct from
      previously-studied populations. METHODS: Peripheral blood samples of 80 OSCC
      patients and 80 healthy individuals were collected for a case-control study
      design. The VEGF gene -460 C/T polymorphism was detected by polymerase chain
      reaction-based restriction analysis. RESULTS: The analysis revealed significant
      differences between normal individuals and patients with OSCC (P < 0.05). The
      distribution of the TT homozygote and the T allele in the patient group was
      significantly greater than in the control group. CONCLUSION: The present study
      provides novel evidence of the role of the VEGF gene -460 C/T polymorphism as a
      suitable genetic marker of OSCC in the Indian population.

PMID- 25051953
TI  - Wear particles and ions from cemented and uncemented titanium-based hip
      prostheses-a histological and chemical analysis of retrieval material.
AB  - Wear debris-induced inflammation is considered to be the main cause for
      periprosthetic osteolysis in total hip replacements (THR). The objective of this
      retrieval study was to examine the tissue reactions and exposure to metal ions
      and wear particles in periprosthetic tissues and blood samples from patients with
      titanium (Ti)-based hip prostheses that were revised due to wear, osteolysis,
      and/or aseptic loosening. Semiquantitative, histological tissue evaluations in 30
      THR-patients revealed numerous wear debris-loaded macrophages, inflammatory
      cells, and necrosis in both groups. Particle load was highest in tissues adjacent
      to loosened cemented Ti stems that contained mainly submicron zirconium (Zr)
      dioxide particles. Particles containing pure Ti and Ti alloy elements were most
      abundant in tissues near retrieved uncemented cups. Polyethylene particles were
      also detected, but accounted only for a small portion of the total particle
      number. The blood concentrations of Ti and Zr were highly elevated in cases with
      high abrasive wear and osteolysis. Our findings indicate that wear particles of
      different chemical composition induced similar inflammatory responses, which
      suggests that particle size and load might be more important than the wear
      particle composition in periprosthetic inflammation and osteolysis.

PMID- 25051954
TI  - Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T
      cells in patients with chronic obstructive pulmonary disease by IL-27/IL
      10/inducible costimulator ligand.
AB  - BACKGROUND: Increased mortality rates in patients with chronic obstructive
      pulmonary disease (COPD) are largely due to severe infectious exacerbations.
      Impaired respiratory immunity is linked to the enhanced susceptibility to
      infections. Dendritic cells (DCs) direct host immune responses toward immunity or
      tolerance. Pulmonary CD1c(+) DCs elicit robust antiviral immune responses in
      healthy subjects. Nevertheless, their functional specialization in patients with
      COPD remains unexplored. OBJECTIVE: We sought to better understand the mechanisms
      that suppress respiratory immunity in patients with COPD by examining the
      immunostimulatory and tolerogenic properties of pulmonary CD1c(+) DCs. METHODS:
      We analyzed the expression of costimulatory and tolerogenic molecules by
      pulmonary CD1c(+) DCs from patients with COPD (CD1c(+)DCCOPD) and former smokers
      without COPD. We isolated lung CD1c(+) DCs and determined their ability to
      stimulate allogeneic T-cell responses. The suppressive effects of lung CD1c(+)
      DCs and CD1c(+) DC-primed T cells on mixed leukocyte reactions were examined. An
      experimental human model of COPD exacerbation was used to investigate the levels
      of critical immunosuppressive molecules in vivo. RESULTS: CD1c(+) DCs from
      patients with COPD hinder T-cell effector functions and favor the generation of
      suppressive IL-10-secreting CD4(+) T cells that function through IL-10 and TGF
      beta. IL-27, IL-10, and inducible T-cell costimulator ligand signaling are
      essential for CD1c(+)DCCOPD-mediated differentiation of IL-10-producing
      suppressive T cells. Exposure of lung CD1c(+) DCs from nonobstructed subjects to
      lungs of patients with COPD confers tolerogenic properties. IL-27 and IL-10
      levels are increased in the lung microenvironment on rhinovirus-induced COPD
      exacerbation in vivo. CONCLUSION: We identify a novel tolerogenic circuit
      encompassing suppressive CD1c(+) DCs and regulatory T cells in patients with COPD
      that might be implicated in impaired respiratory immunity and further highlight
      IL-10 and IL-27 as potent therapeutic targets.

PMID- 25051955
TI  - Pathological features and proposed diagnostic criteria of porcine periweaning
      failure-to-thrive syndrome.
AB  - Porcine periweaning failure-to-thrive syndrome (PFTS) is a clinical syndrome
      characterized by anorexia and progressive debilitation of newly weaned pigs. The
      objectives of the current case-control study were to describe the histopathologic
      features of PFTS in North America and test for selected pathogens in case and
      control pigs on 8 farms allegedly fulfilling the clinical definition of PFTS.
      Based on observations during farm visits, 5 farms fully met the case definition
      (PFTS farms), whereas 3 farms only partially fulfilled the definition (NON-PFTS
      farms). Necropsy and histopathologic examination were performed on case (n = 8 or
      9) and control (n = 4) pigs from each farm. Superficial gastritis, which was
      mainly localized in the fundus and characterized by attenuation of superficial
      foveolar cells, was significantly more frequent in case pigs from PFTS farms
      compared with all the other pigs (odds ratio [OR], 16.7). The same was found for
      thymic atrophy (OR, 30.1) and small intestinal (SI) villous atrophy in the
      duodenum (OR, 28.7), jejunum (OR, 67.4), and ileum (OR, 56.3). All pigs with PFTS
      had at least 2 of these 3 lesions: gastritis, thymic atrophy, and SI villous
      atrophy. PFTS was not associated with any relevant porcine pathogen tested. We
      propose the diagnosis of PFTS be based on the fulfillment of the clinical case
      definition, the presence of the above lesions, and exclusion of other common
      swine diseases and pathogens. However, PFTS can be ruled out if debilitated pigs
      do not have at least 2 of the above 3 lesions.

PMID- 25051956
TI  - Emperipolesis mediated by CD8 T cells is a characteristic histopathologic feature
      of autoimmune hepatitis.
AB  - Emperipolesis has been widely described in patients with autoimmune hepatitis,
      but the significance and the diagnostic value have not been quantitated. The goal
      of this study was to define the features and clinical significance of
      emperipolesis in autoimmune hepatitis (AIH). A retrospective histological
      evaluation of 101 patients with AIH and 184 controls was performed. Confocal
      staining for CD4, CD8, CD19, CD56, CD163, and CD11b, CK8/18 and cleaved caspase-3
      was performed. Emperipolesis was observed in 65.3 % of the patients with AIH in
      haematoxylin and eosin (H&E)-stained slides, which was significantly higher than
      in patients with primary biliary cirrhosis (17.9 %), chronic hepatitis B (14.9
      %), and drug-induced liver injury (25.6 %). Among AIH patients, the patients with
      emperipolesis had significantly higher serum (alanine aminotransferase/aspartate
      aminotransferase [ALT/AST]) levels. Histologically, emperipolesis was associated
      with more severe necroinflammatory features and more advanced fibrosis. The
      lymphocytes in hepatocytes were predominantly as CD8 T cells. Emperipolesis of
      CD8 T cells induced cleaved caspase-3 expression, and was prominent in areas
      apoptosis. Emperipolesis is a characteristic feature of AIH which is often seen
      in conjunction with interface hepatitis, plasmacytic infiltration and hepatocyte
      rosetting and is associated with more severe necroinflammatory and fibrotic
      changes. In AIH, emperipolesis is predominantly mediated by CD8 T cells, appears
      to induce apoptosis and may be another mechanism of autoimmune-mediated
      hepatocyte injury.

PMID- 25051957
TI  - The bromotyrosine derivative ianthelline isolated from the arctic marine sponge
      Stryphnus fortis inhibits marine micro- and macrobiofouling.
AB  - The inhibition of marine biofouling by the bromotyrosine derivative ianthelline,
      isolated from the Arctic marine sponge Stryphnus fortis, is described. All major
      stages of the fouling process are investigated. The effect of ianthelline on
      adhesion and growth of marine bacteria and microalgae is tested to investigate
      its influence on the initial microfouling process comparing with the known marine
      antifoulant barettin as a reference. Macrofouling is studied via barnacle
      (Balanus improvisus) settlement assays and blue mussel (Mytilus edulis)
      phenoloxidase inhibition. Ianthelline is shown to inhibit both marine micro- and
      macrofoulers with a pronounced effect on marine bacteria (minimum inhibitory
      concentration (MIC) values 0.1-10 MUg/mL) and barnacle larval settlement (IC50 =
      3.0 MUg/mL). Moderate effects are recorded on M. edulis (IC50 = 45.2 MUg/mL) and
      microalgae, where growth is more affected than surface adhesion. The effect of
      ianthelline is also investigated against human pathogenic bacteria. Ianthelline
      displayed low micromolar MIC values against several bacterial strains, both Gram
      positive and Gram negative, down to 2.5 MUg/mL. In summary, the effect of
      ianthelline on 20 different representative marine antifouling organisms and seven
      human pathogenic bacterial strains is presented. 

PMID- 25051959
TI  - MR system operator: recommended minimum requirements for performing MRI in human
      subjects in a research setting.
AB  - This article is intended to provide guidelines for the minimum level of safety
      and operational knowledge that an MR system operator should exhibit in order to
      safely perform an MR procedure in a human subject in a research setting. This
      article represents the position of the International Society for Magnetic
      Resonance in Medicine (ISMRM) regarding this important topic and was developed by
      members of this society's MR Safety Committee.

PMID- 25051958
TI  - A calcineurin- and NFAT-dependent pathway is involved in alpha-synuclein-induced
      degeneration of midbrain dopaminergic neurons.
AB  - Parkinson's disease (PD), the most common degenerative movement disorder, is
      caused by a preferential loss of midbrain dopaminergic (mDA) neurons. Both alpha
      synuclein (alpha-syn) missense and multiplication mutations have been linked to
      PD. However, the underlying intracellular signalling transduction pathways of
      alpha-syn-mediated mDA neurodegeneration remain elusive. Here, we show that
      transgenic expression of PD-related human alpha-syn A53T missense mutation
      promoted calcineurin (CN) activity and the subsequent nuclear translocation of
      nuclear factor of activated T cells (NFATs) in mDA neurons. alpha-syn enhanced
      the phosphatase activity of CN in both cell-free assays and cell lines
      transfected with either human wild-type or A53T alpha-syn. Furthermore,
      overexpression of alpha-syn A53T mutation significantly increased the CN
      dependent nuclear import of NFATc3 in the mDA neurons of transgenic mice. More
      importantly, a pharmacological inhibition of CN by cyclosporine A (CsA)
      ameliorated the alpha-syn-induced loss of mDA neurons. These findings demonstrate
      an active involvement of CN- and NFAT-mediated signalling pathway in alpha-syn
      mediated degeneration of mDA neurons in PD. 

PMID- 25051960
TI  - The transcriptional landscape of mouse beta cells compared to human beta cells
      reveals notable species differences in long non-coding RNA and protein-coding
      gene expression.
AB  - BACKGROUND: Insulin producing beta cell and glucagon producing alpha cells are
      colocalized in pancreatic islets in an arrangement that facilitates the
      coordinated release of the two principal hormones that regulate glucose
      homeostasis and prevent both hypoglycemia and diabetes. However, this intricate
      organization has also complicated the determination of the cellular source(s) of
      the expression of genes that are detected in the islet. This reflects a
      significant gap in our understanding of mouse islet physiology, which reduces the
      effectiveness by which mice model human islet disease. RESULTS: To overcome this
      challenge, we generated a bitransgenic reporter mouse that faithfully labels all
      beta and alpha cells in mouse islets to enable FACS-based purification and the
      generation of comprehensive transcriptomes of both populations. This facilitates
      systematic comparison across thousands of genes between the two major endocrine
      cell types of the islets of Langerhans whose principal hormones are of cardinal
      importance for glucose homeostasis. Our data leveraged against similar data for
      human beta cells reveal a core common beta cell transcriptome of 9900+ genes.
      Against the backdrop of overall similar beta cell transcriptomes, we describe
      marked differences in the repertoire of receptors and long non-coding RNAs
      between mouse and human beta cells. CONCLUSIONS: The comprehensive mouse alpha
      and beta cell transcriptomes complemented by the comparison of the global
      (dis)similarities between mouse and human beta cells represent invaluable
      resources to boost the accuracy by which rodent models offer guidance in finding
      cures for human diabetes.

PMID- 25051961
TI  - Analysis of the role of von Willebrand factor, platelet glycoprotein VI-, and
      alpha2beta1-mediated collagen binding in thrombus formation.
AB  - Rare missense mutations in the von Willebrand factor (VWF) A3 domain that disrupt
      collagen binding have been found in patients with a mild bleeding phenotype.
      However, the analysis of these aberrant VWF-collagen interactions has been
      limited. Here, we have developed mouse models of collagen-binding mutants and
      analyzed the function of the A3 domain using comprehensive in vitro and in vivo
      approaches. Five loss-of-function (p.S1731T, p.W1745C, p.S1783A, p.H1786D, A3
      deletion) and 1 gain-of-function (p.L1757A) variants were generated in the mouse
      VWF complementary DNA. The results of these various assays were consistent,
      although the magnitude of the effects were different: the gain-of-function
      (p.L1757A) variant showed consistent enhanced collagen binding whereas the loss
      of-function mutants showed variable degrees of functional deficit. We further
      analyzed the impact of direct platelet-collagen binding by blocking glycoprotein
      VI (GPVI) and integrin alpha2beta1 in our ferric chloride murine thrombosis
      model. The inhibition of GPVI demonstrated a comparable functional defect in
      thrombosis formation to the VWF(-/-) mice whereas alpha2beta1 inhibition
      demonstrated a milder bleeding phenotype. Furthermore, a delayed and markedly
      reduced thrombogenic response was still evident in VWF(-/-), GPVI, and
      alpha2beta1 blocked animals, suggesting that alternative primary hemostatic
      mechanisms can partially rescue the bleeding phenotype associated with these
      defects. 

PMID- 25051965
TI  - Cerebral aneurysm treatment has not shifted to low volume centers.

PMID- 25051966
TI  - Letter in response to Moradiya et al.

PMID- 25051964
TI  - Flow diverter stents for unruptured saccular anterior circulation perforating
      artery aneurysms: safety, efficacy, and short-term follow-up.
AB  - BACKGROUND: Anterior circulation perforating artery aneurysms including anterior
      choroidal artery and lenticulostriate artery aneurysms are rare. Injury to these
      vessels can lead to severe debilitating symptoms. OBJECTIVE: To present a new
      approach to treatment using flow diversion technology. METHODS: Patients treated
      with a Pipeline embolization device (PED) for perforator artery aneurysms at our
      institution between June 2012 and May 2013 were identified and included in our
      retrospective analysis. We evaluated patient vascular risk factors; family
      history of aneurysms; aneurysm characteristics; National Institutes of Health
      Stroke Scale (NIHSS) and modified Rankin Scale (mRS) on admission; and
      angiography follow-up and patient clinical outcome at discharge, 6 months, and 1
      year. RESULTS: We included four patients with a mean age of 59.8 years. Two
      patients had a positive family history of aneurysms. Patient vascular risk
      factors included smoking, dyslipidemia, and hypertension. All patients presented
      with a NIHSS and mRS of 0 on admission. Aneurysms were located at the anterior
      choroidal (n=2) or lenticulostriate artery (n=2) and were treated with a single
      PED. No periprocedural or postprocedural complications occurred. The patients
      were discharged with no change in NHISS or mRS score. Six-month and 1-year follow
      up angiography showed complete aneurysm occlusion. Mild intimal hyperplasia was
      seen in 2 cases at 6 months, but was resolved at the 1-year follow-up. No re
      treatment was necessary. NIHSS and mRS remained 0 at follow-up time points.
      CONCLUSIONS: Our preliminary results show that flow diversion technology is an
      effective and safe therapy for complex, hard-to-treat aneurysms in perforating
      arteries. Larger studies with long-term follow-up are needed to validate our
      promising results.

PMID- 25051963
TI  - Gfi-1 regulates the erythroid transcription factor network through Id2 repression
      in murine hematopoietic progenitor cells.
AB  - Growth factor independence 1 (Gfi-1) is a part of the transcriptional network
      that regulates the development of adult hematopoietic stem and progenitor cells.
      Gfi-1-null (Gfi-1(-/-)) mice have reduced numbers of hematopoietic stem cells
      (HSCs), impaired radioprotective function of hematopoietic progenitor cells
      (HPCs), and myeloid and erythroid hyperplasia. We found that the development of
      HPCs and erythropoiesis, but not HSC function, was rescued by reducing the
      expression of inhibitor of DNA-binding protein 2 (Id2) in Gfi-1(-/-) mice.
      Analysis of Gfi-1(-/-);Id2(+/-) mice revealed that short-term HSCs, common
      myeloid progenitors (CMPs), erythroid burst-forming units, colony-forming units
      in spleen, and more differentiated red cells were partially restored by reducing
      Id2 levels in Gfi-1(-/-) mice. Moreover, short-term reconstituting cells, and, to
      a greater extent, CMP and megakaryocyte-erythroid progenitor development, and red
      blood cell production (anemia) were rescued in mice transplanted with Gfi-1(-/
      );Id2(+/-) bone marrow cells (BMCs) in comparison with Gfi-1(-/-) BMCs. Reduction
      of Id2 expression in Gfi-1(-/-) mice increased the expression of Gata1, Eklf, and
      EpoR, which are required for proper erythropoiesis. Reducing the levels of other
      Id family members (Id1 and Id3) in Gfi-1(-/-) mice did not rescue impaired HPC
      function or erythropoiesis. These data provide new evidence that Gfi-1 is linked
      to the erythroid gene regulatory network by repressing Id2 expression. 

PMID- 25051962
TI  - Regulatory B cells are enriched within the IgM memory and transitional subsets in
      healthy donors but are deficient in chronic GVHD.
AB  - A subset of regulatory B cells (Bregs) in mice negatively regulate T-cell immune
      responses through the secretion of regulatory cytokines such as IL-10 and direct
      cell-cell contact and have been linked to experimental models of autoimmunity,
      inflammation, and cancer. However, the regulatory function of Bregs in human
      disease is much less clear. Here we demonstrate that B cells with
      immunoregulatory properties are enriched within both the CD19(+)IgM(+)CD27(+)
      memory and CD19(+)CD24(hi)CD38(hi) transitional B-cell subsets in healthy human
      donors. Both subsets suppressed the proliferation and interferon-gamma production
      of CD3/CD28-stimulated autologous CD4(+) T cells in a dose-dependent manner, and
      both relied on IL-10 secretion as well as cell-cell contact, likely mediated
      through CD80 and CD86, to support their full suppressive function. Moreover,
      after allogeneic stem cell transplantation, Bregs from patients with chronic
      graft-versus-host disease (cGVHD) were less frequent and less likely to produce
      IL-10 than were Bregs from healthy donors and patients without cGVHD. These
      findings suggest that Bregs may be involved in the pathogenesis of cGVHD and
      support future investigation of regulatory B cell-based therapy in the treatment
      of this disease. 

PMID- 25051967
TI  - MEGDEL Syndrome in a Child From Palestine: Report of a Novel Mutation in SERAC1
      Gene.
AB  - We report the first Palestinian child manifesting with 3-methylglutaconic
      aciduria psychomotor delay, muscle hypotonia, sensori-neural deafness, and Leigh
      like lesions on brain magnetic resonance imaging (MRI), a clinical phenotype that
      is characteristic of MEGDEL syndrome. MEGDEL syndrome was recently found to be
      caused by mutations in SERAC1, encoding a protein essential for mitochondrial
      function, phospholipid remodeling, and intracellular cholesterol trafficking. We
      identified a novel homozygous mutation in SERAC1 gene (c.1018delT) that generates
      frame shift and premature termination of protein translation. Plasma and
      cerebrospinal fluid lactate, plasma alanine, and respiratory chain complexes in
      fresh muscle were normal. This report further expands the genetic spectrum of
      MEGDEL syndrome and adds to the evidence that it is associated with variable
      patterns of respiratory chain abnormalities. 

PMID- 25051968
TI  - A population-based study of communication impairment in cerebral palsy.
AB  - To explore factors associated with communication impairments in children with
      cerebral palsy. Data were obtained on children born between 1999 and 2008 from
      the Quebec Cerebral Palsy Registry (REPACQ). Out of 535 children with cerebral
      palsy, 297 were identified to have communication impairments (55.5%). Of these,
      96 were unable to communicate verbally (32.3%), 195 had some verbal communication
      (65.7%), and 6 were unspecified (2.0%). These children were significantly more
      likely to have a more severe motor deficit (Gross Motor Function Classification
      System levels IV and V and Manual Ability Classification System levels IV and V),
      to have spastic quadriplegia or dyskinetic subtypes of cerebral palsy, and gray
      matter injury on neuroimaging. Communication impairment is a common comorbidity
      in cerebral palsy and is associated with a more severe motor deficit, spastic
      quadriplegic or dyskinetic subtype of cerebral palsy, and gray matter injury on
      neuroimaging. This information allows clinicians to better predict and manage
      communication impairment in children with cerebral palsy. 

PMID- 25051969
TI  - Successful Treatment of Refractory Seizures With Rufinamide in Children With
      Schizencephaly: Report of 3 Cases.
AB  - Schizencephaly is an uncommon malformation of cortical development. Patients with
      schizencephaly present with a broad range of severe neurologic symptoms including
      pharmacoresistant epilepsy. Rufinamide is a new antiepileptic drug approved for
      use as adjunctive therapy of seizures associated with Lennox-Gastaut syndrome and
      it is also effective for refractory partial seizures. We report 3 cases of
      pediatric patients aged 7.2, 8.1, and 10.1 years, respectively, with intractable
      epilepsy associated with bilateral open-lip schizencephaly and septo-optic
      dysplasia. The follow-up ranged from 3.8 to 4.1 years. In our patients, the
      introduction of rufinamide as adjunctive drug led to a dramatic decline in the
      number of seizures and an improvement in EEG epileptic activity without side
      effects. Rufinamide seems to be efficacious and safe in patients with epileptic
      encephalopathies associated with pharmacoresistant epilepsy; further and larger
      clinical reports and controlled studies could confirm the usefulness of this
      anticonvulsant drug.

PMID- 25051970
TI  - Lariat intronic RNAs in the cytoplasm of Xenopus tropicalis oocytes.
AB  - We previously demonstrated that the oocyte nucleus (germinal vesicle or GV) of
      Xenopus tropicalis contains a population of stable RNA molecules derived from the
      introns of most expressed genes. Here we show that similar stable intronic
      sequence (sis) RNAs occur in the oocyte cytoplasm. About 9000 cytoplasmic sisRNAs
      have been identified, all of which are resistant to the exonuclease RNase R.
      About half have been confirmed as lariat molecules and the rest are presumed to
      be lariats, whereas nuclear sisRNAs are a mixture of lariat and linear molecules.
      Cytoplasmic sisRNAs are more abundant on a molar basis than nuclear sisRNAs and
      are derived from short introns, mostly under 1 kb in length. Both nuclear and
      cytoplasmic sisRNAs are transmitted intact to the egg at GV breakdown and persist
      until at least the blastula stage of embryogenesis, when zygotic transcription
      begins. We compared cytoplasmic sisRNAs derived from orthologous genes of X.
      tropicalis and X. laevis, and found that the specific introns from which sisRNAs
      are derived are not conserved. The existence of sisRNAs in the cytoplasm of the
      oocyte, their transmission to the fertilized egg, and their persistence during
      early embryogenesis suggest that they might play a regulatory role in mRNA
      translation. 

PMID- 25051971
TI  - A modified dinucleotide motif specifies tRNA recognition by TLR7.
AB  - RNA can function as a pathogen-associated molecular pattern (PAMP) whose
      recognition by the innate immune system alerts the body to an impending microbial
      infection. The recognition of tRNA as either self or nonself RNA by TLR7 depends
      on its modification patterns. In particular, it is known that the presence of a
      ribose methylated guanosine at position 18, which is overrepresented in self-RNA,
      antagonizes an immune response. Here, we report that recognition extends to the
      next downstream nucleotide and the effectively recognized molecular detail is
      actually a methylated dinucleotide. The most efficient nucleobases combination of
      this motif includes two purines, while pyrimidines diminish the effect of ribose
      methylation. The constraints of this motif stay intact when transposed to other
      parts of the tRNA. The results argue against a fixed orientation of the tRNA
      during interaction with TLR7 and, rather, suggest a processive type of
      inspection. 

PMID- 25051972
TI  - A remarkably stable kissing-loop interaction defines substrate recognition by the
      Neurospora Varkud Satellite ribozyme.
AB  - Kissing loops are tertiary structure elements that often play key roles in
      functional RNAs. In the Neurospora VS ribozyme, a kissing-loop interaction
      between the stem-loop I (SLI) substrate and stem-loop V (SLV) of the catalytic
      domain is known to play an important role in substrate recognition. In addition,
      this I/V kissing-loop interaction is associated with a helix shift in SLI that
      activates the substrate for catalysis. To better understand the role of this
      kissing-loop interaction in substrate recognition and activation by the VS
      ribozyme, we performed a thermodynamic characterization by isothermal titration
      calorimetry using isolated SLI and SLV stem-loops. We demonstrate that preshifted
      SLI variants have higher affinity for SLV than shiftable SLI variants, with an
      energetic cost of 1.8-3 kcal/mol for the helix shift in SLI. The affinity of the
      preshifted SLI for SLV is remarkably high, the interaction being more stable by 7
      8 kcal/mol than predicted for a comparable duplex containing three Watson-Crick
      base pairs. The structural basis of this remarkable stability is discussed in
      light of previous NMR studies. Comparative thermodynamic studies reveal that
      kissing-loop complexes containing 6-7 Watson-Crick base pairs are as stable as
      predicted from comparable RNA duplexes; however, those with 2-3 Watson-Crick base
      pairs are more stable than predicted. Interestingly, the stability of
      SLI/ribozyme complexes is similar to that of SLI/SLV complexes. Thus, the I/V
      kissing loop interaction represents the predominant energetic contribution to
      substrate recognition by the trans-cleaving VS ribozyme. 

PMID- 25051973
TI  - A bridge between the aminoacylation and editing domains of leucyl-tRNA synthetase
      is crucial for its synthetic activity.
AB  - Leucyl-tRNA synthetases (LeuRSs) catalyze the linkage of leucine with tRNA(Leu).
      LeuRS contains a catalysis domain (aminoacylation) and a CP1 domain (editing).
      CP1 is inserted 35 A from the aminoacylation domain. Aminoacylation and editing
      require CP1 to swing to the coordinated conformation. The neck between the CP1
      domain and the aminoacylation domain is defined as the CP1 hairpin. The location
      of the CP1 hairpin suggests a crucial role in the CP1 swing and domain-domain
      interaction. Here, the CP1 hairpin of Homo sapiens cytoplasmic LeuRS (hcLeuRS)
      was deleted or substituted by those from other representative species. Lack of a
      CP1 hairpin led to complete loss of aminoacylation, amino acid activation, and
      tRNA binding; however, the mutants retained post-transfer editing. Only the CP1
      hairpin from Saccharomyces cerevisiae LeuRS (ScLeuRS) could partly rescue the
      hcLeuRS functions. Further site-directed mutagenesis indicated that the
      flexibility of small residues and the charge of polar residues in the CP1 hairpin
      are crucial for the function of LeuRS. 

PMID- 25051974
TI  - Perforated sigmoid diverticulitis in a lumbar hernia after iliac crest bone graft
      -a case report.
AB  - BACKGROUND: The combination of perforated diverticulitis in a lumbar hernia
      constitutes an extremely rare condition. CASE PRESENTATION: We report a case of a
      66 year old Caucasian woman presenting with perforated sigmoid diverticulitis
      localized in a lumbar hernia following iliac crest bone graft performed 18 years
      ago. Emergency treatment consisted of laparoscopic peritoneal lavage. Elective
      sigmoid resection was scheduled four months later. At the same time a
      laparoscopic hernia repair with a biologic mesh graft was performed. CONCLUSION:
      This case shows a very seldom clinical presentation of lumbar hernia. Secondary
      colonic resection and concurrent hernia repair with a biologic implant have
      proven useful in treating this rare condition.

PMID- 25051975
TI  - The mTOR kinase inhibitors polarize glioma-activated microglia to express a M1
      phenotype.
AB  - BACKGROUND: Increased activation of mammalian target of rapamycin (mTOR) is
      observed in numerous human cancers. Recent studies on the glioma kinome have
      identified several deregulated pathways that converge and activate mTOR. The
      available evidence on the role of microglia in CNS cancers would suggest a dual
      role, a tumoricidal role and -on the contrary- a role favoring tumor growth.
      METHODS: In the present paper, we have compared the effects of MUM concentrations
      of rapamycin (RAPA) and its analog, RAD001 (RAD), on activated microglia; the
      latter was obtained by exposing cells to conditioned medium harvested either from
      inflammatory activated glioma cells (LI-CM) or from glioma cells kept under basal
      conditions (C-CM). RESULTS: Here we show that the inhibition of mTOR polarizes
      glioma-activated microglial cells towards the M1 phenotype, with cytotoxic
      activities, preventing the induction of the M2 status that promotes tumor growth.
      In fact RAPA and RAD significantly increased iNOS expression and activity, while
      on the same time significantly reducing IL-10 gene expression induced by C-CM,
      thus suggesting that the drugs prevent the acquisition of a M2 phenotype in
      response to glioma factors promoting a classic M1 activation. Similar results
      were obtained using the conditioned media obtained after glioma stimulation with
      LPS-IFNgamma (LI-CM), which was found to induce a mixture of M1 and M2a/b
      polarization phenotypes. In these conditions, the inhibition of mTOR led to a
      significant up-regulation of iNOS, and in parallel to the down-regulation of both
      ARG and IL-10 gene expression. CONCLUSIONS: These data suggest that mTOR
      inhibition may prevent glioma induced M2 polarization of microglial cells and
      increase their cytotoxic potential, possibly resulting in antitumor actions.

PMID- 25051976
TI  - Comparative study of hepatic venography using non-linear-blending images,
      monochromatic images and low-voltage images of dual-energy CT.
AB  - OBJECTIVE: To investigate the use of non-linear-blending and monochromatic dual
      energy CT (DECT) images to improve the image quality of hepatic venography.
      METHODS: 82 patients undergoing abdominal DECT in the portal venous phase were
      enrolled. For each patient, 31 data sets of monochromatic images and 7 data sets
      of non-linear-blending images were generated. The data sets of the non-linear
      blending and monochromatic images with the best contrast-to-noise ratios (CNRs)
      for hepatic veins were selected and compared with the images obtained at 80 kVp
      and a simulated 120 kVp. The subjective image quality of the hepatic veins was
      evaluated using a four-point scale. The image quality of the hepatic veins was
      analysed using signal-to-noise ratio (SNR) and CNR values. RESULTS: The optimal
      CNR between hepatic veins and the liver was obtained with the non-linear-blending
      images. Compared with the other three groups, there were significant differences
      in the maximum CNR, the SNR, the subjective ratings and the minimum background
      noise (p < 0.001). A comparison of the monochromatic and 80-kVp images revealed
      that the CNR and subjective ratings were both improved (p < 0.001). There was no
      significant difference in the CNR or subjective ratings between the simulated 120
      kVp group and the control group (p = 0.090 and 0.053, respectively). CONCLUSION:
      The non-linear-blending technique for acquiring DECT provided the best image
      quality for hepatic venography. ADVANCES IN KNOWLEDGE: DECT can enhance the
      contrast of hepatic veins and the liver, potentially allowing the wider use of
      low-dose contrast agents for CT examination of the liver.

PMID- 25051977
TI  - Meta-analysis of CT-guided transthoracic needle biopsy for the evaluation of the
      ground-glass opacity pulmonary lesions.
AB  - OBJECTIVE: This meta-analysis is to determine the overall diagnostic yield of CT
      guided transthoracic needle biopsy (TNB) of ground-glass opacity (GGO) lesions.
      METHODS: A PubMed search was performed using "ground-glass opacity" crossed with
      "core biopsy" and "needle biopsy". Test performance characteristics with the use
      of forest plots, summary receiver operating characteristic curves and bivariate
      random effects models were summarized. Adverse events, if reported, were
      recorded. RESULTS: Our search identified 52 citations, of which 6 diagnostic
      studies evaluated 341 patients. Pooled specificity estimates were 0.94 [95%
      confidence interval (CI), 0.84-0.98] and sensitivity estimates were 0.92 (95% CI,
      0.88-0.95), respectively. The positive likelihood ratio was 11.27 (95% CI, 4.2
      30.6), the negative likelihood ratio was 0.1 (95% CI, 0.06-0.19), the diagnostic
      odds ratio was 131.38 (95% CI, 39.6-436.0) and the area under the curve was 0.97.
      CONCLUSION: Our data suggest that the CT-guided TNB is likely to be a useful tool
      for tissue diagnosis and may serve as an alternative for further patient
      management with GGO lesions. However, considering the limited studies and
      patients included, large scale studies are needed to verify these findings.
      ADVANCES IN KNOWLEDGE: Some studies about CT-guided TNB of GGO lesions have been
      published, most have been small, single-institution case series. To our
      knowledge, our study is the first systematic analysis about CT-guided TNB of GGO
      lesions.

PMID- 25051979
TI  - BJR brachytherapy dosimetry special feature.

PMID- 25051978
TI  - The role of texture analysis in imaging as an outcome predictor and potential
      tool in radiotherapy treatment planning.
AB  - Predicting a tumour's response to radiotherapy prior to the start of treatment
      could enhance clinical care management by enabling the personalization of
      treatment plans based on predicted outcome. In recent years, there has been
      accumulating evidence relating tumour texture to patient survival and response to
      treatment. Tumour texture could be measured from medical images that provide a
      non-invasive method of capturing intratumoural heterogeneity and hence could
      potentially enable a prior assessment of a patient's predicted response to
      treatment. In this article, work presented in the literature regarding texture
      analysis in radiotherapy in relation to survival and outcome is discussed.
      Challenges facing integrating texture analysis in radiotherapy planning are
      highlighted and recommendations for future directions in research are suggested. 

PMID- 25051980
TI  - Molecular cloning, expression profiles, and characterization of a novel
      polyphenol oxidase (PPO) gene in Hevea brasiliensis.
AB  - The polyphenol oxidase (PPO) is involved in undesirable browning in many plant
      foods. Although the PPOs have been studied by several researchers, the isolation
      and expression profiles of PPO gene were not reported in rubber tree. In this
      study, a new PPO gene, HbPPO, was isolated from Hevea brasiliensis. The sequence
      alignment showed that HbPPO indicated high identities to plant PPOs and belonged
      to dicot branch. The cis-acting regulatory elements related to stress/hormone
      responses were predicted in the promoter region of HbPPO. Real-time RT-PCR
      analyses showed that HbPPO expression varied widely depending on different
      tissues and developmental stages of leaves. Besides being associated with tapping
      panel dryness, the HbPPO transcripts were regulated by ethrel, wounding, H2O2,
      and methyl jasmonate treatments. Moreover, the correlation between latex
      coagulation rate and PPO activity was further confirmed in this study. Our
      results lay the foundation for further analyzing the function of HbPPO in rubber
      tree. 

PMID- 25051982
TI  - Experience of a peer physical examination policy within a New Zealand medical
      programme.

PMID- 25051981
TI  - EZH2 expression correlates with locoregional recurrence after radiation in
      inflammatory breast cancer.
AB  - BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a member of the polycomb group
      proteins, has been shown to promote cancer progression and breast cancer stem
      cell (CSC) expansion. Breast CSCs are associated with resistance to radiation in
      inflammatory breast cancer (IBC), a rare but aggressive variant of breast cancer.
      In this retrospective study, we examined the clinical role of EZH2 in
      locoregional recurrence (LRR) of IBC patients treated with radiation. PATIENTS
      AND METHODS: 62 IBC patients who received radiation (7 pre-operative, 55 post
      operative) and had adequate follow up to assess LRR were the subject of this
      study. Positive EZH2 status was defined as nuclear immunohistochemical staining
      in at least 10% of invasive cancer cells. Association of EZH2 expression with
      clinicopathologic features were evaluated using the Chi-square statistic and
      actuarial LRR free survival (LRFS) was determined using the Kaplan-Meier method.
      RESULTS: The median follow-up for this cohort was 33.7 months, and the 5-year
      overall LRFS rate was 69%. Of the 62 patients, 16 (25.8%) had LRR, and 15 out of
      16 LRR occurred in EZH2 expressing cases. Univariate analysis indicated that
      patients who had EZH2-positive IBC had a significantly lower 5-year locoregional
      free survival (LRFS) rate than patients who had EZH2-negative IBC (93.3% vs.
      59.1%; P = 0.01). Positive EZH2 expression was associated significantly with
      negative ER status (97.1% in ER- vs 48.1% in ER+; P < 0.0001) and triple-negative
      receptor status (P = 0.0001) and all triple-negative tumors were EZH2-positive.
      In multivariate analysis, only triple negative status remained an independent
      predictor of worse LRFS (hazard ratio 5.64, 95% CI 2.19 - 14.49, P < 0.0001).
      CONCLUSIONS: EZH2 correlates with locoregional recurrence in IBC patients who
      received radiation treatment. EZH2 expression status may be used in addition to
      receptor status to identify a subset of patients with IBC who recur locally in
      spite of radiation and may benefit from enrollment in clinical trials testing
      radiosensitizers.

PMID- 25051983
TI  - Neutrophil derived microvesicles: emerging role of a key mediator to the immune
      response.
AB  - In response to infection and trauma, exquisite control of the innate inflammatory
      response is necessary to promote an anti-microbial response and minimize tissue
      injury. Over the course of the host response, activated leukocytes are essential
      for the initial response and can later become unresponsive or undergo apoptosis.
      Leukocytes, along the continuum of activation to apoptosis, have been shown to
      generate microvesicles. These vesicles can range in size from 0.1 to 1.0 MUm and
      can retain proteins, RNA and DNA of their parent cells. Importantly, neutrophil
      derived microvesicles (NDMV) are robustly increased under inflammatory
      conditions. The aim of this review is to summarize the research to date upon
      NDMVs. This will include describing under which disease states NDMVs are
      increased, mechanisms underlying formation, and the impact of these vesicles upon
      cellular targets. Altogether, increased awareness of NDMVs during the host innate
      response may allow for diagnostic tools as well as potential novel therapies
      during infection and trauma.

PMID- 25051984
TI  - Cloning and characterization of a mannose binding C-type lectin gene from
      salivary gland of Aedes albopictus.
AB  - BACKGROUND: The studies on sialomes have shown that hematophagous mosquito saliva
      consists of a lot of pharmacologically active proteins, in which C-type lectins
      have been identified and regarded as an important component of saliva. The
      previous studies showed that C-type lectins play crucial roles not only in innate
      immunity but also in promoting disease transmission in mammals. However, the
      function and mechanism of C-type lectins from the mosquito sialome is still
      elusive. METHODS: A putative C-type lectin gene (Aalb_CTL1) was cloned and
      expressed from Aedes albopictus by RT-PCR. The deduced amino acid sequence was
      analyzed by bioinformatic methods. The gene expression profiles in different
      tissues and various blood-fed stages of Ae. albopictus were examined by Real-Time
      qRT-PCR and the biological functions of the recombined mature Aalb_CTL1 were
      tested by hemagglutination and sugar inhibitory agglutination assays. Moreover,
      the capabilities of rAalb_CTL1 against microorganisms were measured by microbial
      agglutination assay. RESULTS: The full-length Open reading frame (ORF) of
      Aalb_CTL1 consisted of 462 bp, encoding 153 amino acid residues. The deduced
      amino acid sequence contained a putative signal peptide of 19 amino acids. It
      also contained a CRD domain with a WND (Trp137-Asn138-Asp-139) motif that needed
      calcium for the hemagglutinating activity and an imperfect EPS (Glu128-Pro129
      Ser130) motif that had a predicted ligand binding specificity for mannose. The
      mRNA level of Aalb_CTL1 was much higher in female mosquito salivary gland than
      those in fat body and midgut which was down-regulated in salivary gland after
      blood feeding. The rAalb_CTL1 contained not only hemagglutinating activity and a
      high affinity with mannose but also agglutinating activity against yeast C.
      albicans and Gram-positive bacteria S. aureus in Ca2+ dependent manner.
      CONCLUSION: Aalb_CTL1 was a mannose-binding C-type lectin and constituted one of
      the important components in saliva of Ae. albopictus, which could be involved in
      the defense against yeast and Gram-positive bacteria infection.

PMID- 25051985
TI  - Drl.3 governs primitive hematopoiesis in zebrafish.
AB  - The molecular program controlling hematopoietic differentiation is not fully
      understood. Here, we describe a family of zebrafish genes that includes a novel
      hematopoietic regulator, draculin-like 3 (drl.3). We found that drl.3 is
      expressed in mesoderm-derived hematopoietic cells and is retained during
      erythroid maturation. Moreover, drl.3 expression correlated with erythroid
      development in gata1a- and spi1b-depleted embryos. Loss-of-function analysis
      indicated that drl.3 plays an essential role in primitive erythropoiesis and, to
      a lesser extent, myelopoiesis that is independent of effects on vasculature,
      emergence of primitive and definitive progenitor cells and cell viability. While
      drl.3 depletion reduced gata1a expression and inhibited erythroid development,
      enforced expression of gata1a was not sufficient to rescue erythropoiesis,
      indicating that the regulation of hematopoiesis by drl.3 extends beyond control
      of gata1a expression. Knockdown of drl.3 increased the proportion of less
      differentiated, primitive hematopoietic cells without affecting proliferation,
      establishing drl.3 as an important regulator of primitive hematopoietic cell
      differentiation. 

PMID- 25051987
TI  - A model for developing, evaluating, and disseminating best practices in education
      and training.
AB  - With the shift toward team-based translational science came recognition that
      existing strategies for training individual investigators and retaining them in
      the biomedical workforce would be inadequate. To support this shift, it is
      important to: develop innovative strategies to educate and train diverse members
      of research teams; evaluate those programs; and disseminate best practices
      broadly. We have developed a four-phase model to facilitate the development,
      evaluation, and widespread dissemination of innovative strategies to train the
      biomedical research workforce. Phase I (Innovate) involves small scale trials of
      programs to address perceived training needs or new methods of delivery. Phase II
      (Incubate) refines and evaluates promising Phase I activities on a larger scale.
      Phase III (Translate) seeks to replicate initial successes either locally (Phase
      IIIa) or with other interested institutions (Phase IIIb). Phase IV (Disseminate)
      assesses whether identified local best practices can have success on a broader
      scale. We present specific examples from our own experience that demonstrate the
      utility of this model, and then conclude with opportunities and challenges
      related to the education and training of this workforce. 

PMID- 25051986
TI  - Rcor2 underexpression in senescent mice: a target for inflammaging?
AB  - BACKGROUND: Aging is characterized by a low-grade systemic inflammation that
      contributes to the pathogenesis of neurodegenerative disorders such as
      Alzheimer's disease (AD). However, little knowledge is currently available on the
      molecular processes leading to chronic neuroinflammation. In this context, recent
      studies have described the role of chromatin regulators in inflammation and
      longevity including the REST corepressor (Rcor)-2 factor, which seems to be
      involved in an inflammatory suppressive program. METHODS: To assess the impact of
      Rcor2 in age-related inflammation, gene expression levels were quantified in
      different tissues and ages of the spontaneous senescence-accelerated P8 mouse
      (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8
      and R1 astrocyte cultures was used to determine Rcor2 involvement in the
      modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment
      on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.
      RESULTS: P8 mice presented a dramatic decrease in Rcor2 gene expression compared
      with R1 controls in splenocytes, an alteration also observed in the brain cortex,
      hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes
      was accompanied by an increased basal expression of the interleukin (Il)-6 gene.
      Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the
      hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf
      alpha), Il1-beta and Il6 genes. A negative correlation between Rcor2 and Il6 gene
      expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2
      by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression
      while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS
      activation provoked a further downregulation of Rcor2 and an amplified induction
      of Il6 in siRcor2-tranfected astrocytes. CONCLUSIONS: Data presented here show
      interplay between Rcor2 downregulation and increased inflammation and suggest
      that Rcor2 may be a key regulator of inflammaging.

PMID- 25051988
TI  - Gene cloning and biochemical characterization of eryngase, a serine
      aminopeptidase of Pleurotus eryngii belonging to the family S9 peptidases.
AB  - Pleurotus eryngii serine aminopeptidase that has peptide bond formation activity,
      redesignated as eryngase, was cloned and expressed. Eryngase has a family S9
      peptidase unit in the C-terminal region having a catalytic triad of Ser, Asp, and
      His. In the phylogenetic relations among the subfamilies of family S9 peptidase
      (S9A, prolyl oligopeptidase; S9B, dipeptidyl peptidase; S9C, acylaminoacyl
      peptidase; S9D, glutamyl endopeptidase), eryngase existed alone in the neighbor
      of S9C subfamily. Mutation of the active site Ser524 of the eryngase with Ala
      eliminated its catalytic activity. In contrast, S524C mutant maintained low
      catalytic activity. Investigation of aminolysis activity using l-Phe-NH2 as a
      substrate showed that S524C mutant exhibited no hydrolysis reaction but
      synthesized a small amount of l-Phe-l-Phe-NH2 by the catalysis of aminolysis. In
      contrast, wild-type eryngase hydrolyzed the product of aminolysis l-Phe-l-Phe
      NH2. Results show that the S524C mutant preferentially catalyzed aminolysis when
      on an l-Phe-NH2 substrate.

PMID- 25051989
TI  - A design to investigate the feasibility and effects of partnered ballroom dancing
      on people with Parkinson disease: randomized controlled trial protocol.
AB  - BACKGROUND: Self-help and physical leisure activities has become increasingly
      important in the maintenance of safe and functional mobility among an
      increasingly elderly population. Preventing the cycle of deterioration, falling,
      inactivity, dependency, and secondary complications in people with Parkinson
      disease (PD) is a priority. Research has shown that people with PD are interested
      in dance and although the few existing trials are small, initial proof of
      principle trials from the United States have demonstrated beneficial effects on
      balance control, gait, and activity levels. To our knowledge, there has been no
      research into long-term effects, cost effectiveness, the influence on spinal
      posture and turning, or the personal insights of dance participants. OBJECTIVE:
      The purpose of this study was to determine the methodological feasibility of
      conducting a definitive phase III trial to evaluate the benefits of dance in
      people with PD. We will build on the proof of principle trials by addressing gaps
      in knowledge, focusing on areas of greatest methodological uncertainty; the
      choice of dances and intensity of the program; for the main trial, the
      availability of partners, the suitability of the currently envisaged primary
      outcomes, balance and spinal posture; and the key costs of delivering and
      participating in a dance program to inform economic evaluation. METHODS: Fifty
      participants (mild-to-moderate condition) will be randomized to the control
      (usual care) or experimental (dance plus usual care) groups at a ratio of 15:35.
      Dance will be taught by professional teachers in a dance center in the South of
      England. Each participant in the experimental group will dance with his or her
      spouse, a friend, or a partner from a bank of volunteers. A blinded assessor will
      complete clinical measures and self-reported ability at baseline, and at 3 and 6
      months after randomization. A qualitative study of a subgroup of participants and
      partners will examine user's views about the appropriateness and acceptability of
      the intervention, assessment protocol, and general trial procedures. Procedures
      for an economic evaluation of dance for health care will be developed for the
      main trial. RESULTS: Recruitment began in January 2013 and the last participant
      is expected to complete the trial follow-up in June 2014. CONCLUSIONS: Findings
      from our study may provide novel insights into the way people with PD become
      involved in dance, their views and opinions, and the suitability of our primary
      and secondary outcomes. TRIAL REGISTRATION: International Standard Randomized
      Controlled Trial Number (ISRCTN): 63088686; http://www.controlled
      trials.com/ISRCTN63088686/63088686 (Archived by WebCite at
      http://www.webcitation.org/6QYyjehP7).

PMID- 25051990
TI  - Altered lignin biosynthesis using biotechnology to improve lignocellulosic
      biofuel feedstocks.
AB  - Lignocellulosic feedstocks can be converted to biofuels, which can conceivably
      replace a large fraction of fossil fuels currently used for transformation.
      However, lignin, a prominent constituent of secondary cell walls, is an
      impediment to the conversion of cell walls to fuel: the recalcitrance problem.
      Biomass pretreatment for removing lignin is the most expensive step in the
      production of lignocellulosic biofuels. Even though we have learned a great deal
      about the biosynthesis of lignin, we do not fully understand its role in plant
      biology, which is needed for the rational design of engineered cell walls for
      lignocellulosic feedstocks. This review will recapitulate our knowledge of lignin
      biosynthesis and discuss how lignin has been modified and the consequences for
      the host plant. 

PMID- 25051991
TI  - Mitochondrial dynamics and the innate antiviral immune response.
AB  - The innate immune system has a key role in the mammalian immune response. In the
      cytosol, RNA viruses are sensed by the retinoic acid-inducible gene-I-like
      receptors, which trigger a complex signaling cascade in which mitochondrial
      antiviral signaling protein plays a central role in mediating the innate host
      response through the induction of antiviral and inflammatory responses. Hence,
      the mitochondrion is now emerging as a fundamental hub for innate antiviral
      immunity beyond its known roles in metabolic processes and the control of
      programmed cell death. This review summarizes the findings related to
      mitochondrial antiviral signaling protein, and mitochondria and their dynamics,
      in the innate immune response to RNA viruses. 

PMID- 25051992
TI  - Travel behavior and deferral of Dutch blood donors: consequences for donor
      availability.
AB  - BACKGROUND: Donors returning from areas with outbreaks of infectious diseases may
      donate infectious blood back home. Geographic donor deferral is an effective
      measure to ensure the blood safety, but donor deferral may pose a threat for the
      blood supply especially after holiday seasons. Insight into the travel behavior
      of blood donors is a first step to define appropriate deferral strategies. This
      study describes the travel behavior of Dutch donors, the actual deferral, and the
      consequences of deferral strategies on donor availability. STUDY DESIGN AND
      METHODS: A questionnaire designed to assess travel behavior (destination,
      frequency, and duration of travels) was sent to 2000 Dutch donors. The impact of
      travel deferral policies on donor availability was calculated, expressed as
      proportionate decrease in donor availability. The deferral policies considered
      were 1) deferral based on entire countries instead of affected regions where an
      infection is prevalent and 2) deferral after any travel outside Europe
      ("universal deferral"). RESULTS: Of the 1340 respondents, 790 (58.9%) donors
      traveled within Europe only, 61 (4.6%) outside Europe only, and 250 (18.7%)
      within and outside Europe. The deferral for entire countries and universal
      deferral would lead to 11.1 and 11.4% decrease in donor availability,
      respectively. CONCLUSION: Most Dutch donors traveled outside the Netherlands,
      while 23.2% traveled outside Europe. Universal deferral resulted in an additional
      decrease in donor availability of 0.3% compared with deferral for entire
      countries instead of affected regions where an infection is prevalent. Thus, the
      universal deferral could be considered as a simpler and safer measure.

PMID- 25051994
TI  - Case review analysis of operating room decisions to cancel surgery.
AB  - BACKGROUND: Cancellation of surgery close to scheduled time causes a waste of
      healthcare resources. The current study analyzes surgery cancellations occurring
      after the patient has been prepared for the operating room, in order to see
      whether improvements in the surgery planning process may reduce the number of
      cancellations. METHODS: In a retrospective chart review of operating room surgery
      cancellations during the period from 2006 to 2011, cancellations were divided
      into the following categories: inadequate NPO; medical; surgical; system; airway;
      incomplete evaluation. The relative use of these reasons in relation to patient
      age and surgical department was then evaluated. RESULTS: Forty-one percent of
      cancellations were for other than medical reasons. Among these, 17.7% were due to
      incomplete evaluation, and 8.2% were due to family issues. Sixty seven percent of
      cancelled cases eventually received surgery. The relative use of individual
      reasons for cancellation varied with patient age and surgical department. The
      difference between cancellations before and after anesthesia was dependent on the
      causes of cancellation, but not age, sex, ASA status, or follow-up procedures
      required. CONCLUSION: Almost half of the cancellations were not due to medical
      reasons, and these cancellations could be reduced by better administrative and
      surgical planning and better communication with the patient and/or his family.

PMID- 25051993
TI  - Highlights of glycosylation and adhesion related genes involved in myogenesis.
AB  - BACKGROUND: Myogenesis is initiated by myoblast differentiation and fusion to
      form myotubes and muscle fibres. A population of myoblasts, known as satellite
      cells, is responsible for post-natal growth of muscle and for its regeneration.
      This differentiation requires many changes in cell behaviour and its surrounding
      environment. These modifications are tightly regulated over time and can be
      characterized through the study of changes in gene expression associated with
      this process. During the initial myogenesis steps, using the myoblast cell line
      C2C12 as a model, Janot et al. (2009) showed significant variations in expression
      for genes involved in pathways of glycolipid synthesis. In this study we used
      murine satellite cells (MSC) and their ability to differentiate into myotubes or
      early fat storage cells to select glycosylation related genes whose variation of
      expression is myogenesis specific. RESULTS: The comparison of variant genes in
      both MSC differentiation pathways identified 67 genes associated with myogenesis.
      Comparison with data obtained for C2C12 revealed that only 14 genes had similar
      expression profiles in both cell types and that 17 genes were specifically
      regulated in MSC. Results were validated statistically by without a priori
      clustering. Classification according to protein function encoded by these 31
      genes showed that the main regulated cellular processes during this
      differentiation were (i) remodeling of the extracellular matrix, particularly,
      sulfated structures, (ii) down-regulation of O-mannosyl glycan biosynthesis, and
      (iii) an increase in adhesion protein expression. A functional study was
      performed on Itga11 and Chst5 encoding two highly up-regulated proteins. The
      inactivation of Chst5 by specific shRNA delayed the fusion of MSC. By contrast,
      the inactivation of Itga11 by specific shRNA dramatically decreased the fusion
      ability of MSC. This result was confirmed by neutralization of Itga11 product by
      specific antibodies. CONCLUSIONS: Our screening method detected 31 genes specific
      for myogenic differentiation out of the 383 genes studied. According to their
      function, interaction networks of the products of these selected genes converged
      to cell fusion. Functional studies on Itga11 and Chst5 demonstrated the
      robustness of this screening.

PMID- 25051995
TI  - Telehealth: experience of the first 120 consultations delivered from a new
      refugee telehealth clinic.
AB  - BACKGROUND: In 2011, the Australian Government introduced Medicare item numbers
      for telehealth consultations. This is a rapidly expanding method of healthcare
      provision. AIMS: We assessed the demographic and disease profile of refugee
      patients attending a new telehealth clinic, and calculated the patient travel
      avoided. We examined technical challenges and assessed the performance of two
      videoconferencing solutions using different bandwidth and latencies. METHODS: We
      audited the first 120 patients attending the telehealth clinic. During
      consultations, the patient was with the general practitioner (GP) and linked by
      internet videoconference using VIDYO, GoToMeeting or Skype, to the specialist at
      a tertiary referral hospital. Travel avoided was calculated and technical
      problems were assessed by the participating specialist. Bandwidth and latency
      variations were examined within a university broadband testing facility. RESULTS:
      The two most frequently managed conditions were hepatitis C and latent
      tuberculosis. Twenty-nine different GP were included and 42 consultations
      required an interpreter. Nearly 500 km of travel and 127 kg of CO(2) production
      was avoided per consultation. Technical issues were faced in 25% of
      consultations, most frequently sound problems and connections dropping out. A
      bandwidth of at least 512 kbps and latency of no more than 300 ms was necessary
      to conduct an adequate multipoint videoconference. CONCLUSIONS: Telehealth using
      videoconferencing adds a new component to care of refugee and immigrant patients
      settling in regional areas. Telehealth will be improved by changes to improve
      simplicity and standardisation of videoconferencing, but requires ongoing
      Medicare funding to allow sufficient administrative support.

PMID- 25051996
TI  - Ultrasonographic imaging of the cervical thoracic duct in children with
      congenital or acquired heart disease.
AB  - Conditions that increase central venous pressure lead to secondary dilation of
      the thoracic duct and impaired lymphatic circulation. We report the use of
      ultrasound to directly image the cervical part of the thoracic duct in children
      without the need for invasive techniques or contrast agents. Systematic
      evaluation of the thoracic duct may be useful in cardiovascular conditions with
      congestion of the lymphatic system such as single ventricle following Glenn or
      Fontan procedures. 

PMID- 25051997
TI  - Visualization of Zn2+ ions in live zebrafish using a luminescent iridium(III)
      chemosensor.
AB  - A novel luminescent cyclometalated iridium(III) complex-based chemosensor (1)
      bearing a zinc-specific receptor, tris(2-pyridylmethyl)amine, and the 3-phenyl-1H
      pyrazole ligand has been designed and synthesized. Upon the addition of Zn(2+)
      ions to a solution of iridium(III) complex 1, a pronounced luminescence color
      change from blue to green can be observed, which may be attributed to the
      suppression of photoinduced electron transfer upon complexation of complex 1 with
      Zn(2+) ions. The interaction of iridium(III) complex 1 with Zn(2+) ions was
      investigated by UV-vis absorption titration, emission titration, and (1)H NMR
      titration. Furthermore, the iridium(III) complex 1 exhibited good selectivity for
      Zn(2+) over 13 other common metal ions, including K(+), Ag(+), Na(+), Ni(2+),
      Fe(3+), Hg(2+), Cd(2+), Mg(2+), Ca(2+), Cu(2+), Mn(2+), Co(2+), and Pb(2+) ions.
      The practical application of the iridium(III) complex 1 in visualizing
      intracellular Zn(2+) distribution in live zebrafish was also demonstrated. 

PMID- 25051999
TI  - Perceived trustworthiness of faces drives trust behaviour in children.
AB  - Facial appearances can powerfully influence adults' trust behaviour, despite
      limited evidence that these cues constitute honest signals of trustworthiness. It
      is not clear, however, whether the same is also true for children. The current
      study investigated whether, like adults, 5-year-olds and 10-year-olds are more
      likely to place their trust in partners that look trustworthy than those that
      look untrustworthy. A second, closely related question was whether children also
      explicitly value the information from face cues when making trust decisions. We
      investigated these questions using Token Quest: an economic trust game that gave
      participants the opportunity to make investments with a series of partners who
      might (or might not) repay their trust with large returns. These interactions
      occurred under different conditions, including one in which participants were
      shown the face of each partner and another in which they could 'purchase' access
      to faces with a portion of their investment capital. Results indicated that, like
      adults, 10-year-old children selectively placed their trust in those partners
      they perceived as looking trustworthy and many were willing to 'pay' to purchase
      access to these face cues during the trust game. We observed a similar profile of
      trust behaviour in 5-year-olds, with no significant group difference in the
      impact of face cues on behaviour across the three age groups. Together, these
      findings indicate that the influence of face cues on trust behaviour emerges
      early, and highlight a capacity for sophisticated social cognition in young
      children. 

PMID- 25052000
TI  - Cognitive function and quality of life in mild thyroid hormone deficiency.
AB  - Subclinical hypothyroidism (sHT) is very common in general population, especially
      in women and older people. sHT individuals may experience symptoms that resemble
      those observed in overt hypothyroidism, resulting in impaired quality of life
      (QOL). Asymptomatic patients may suffer a reduction in perceived health status
      due to the awareness of disease. Cognitive function represents one of the most
      important domains of the QOL questionnaires. Given the intrinsic relationship
      between cognitive status and QOL it is worth to address these topics together, in
      a systematic review of the literature. Thus, we reviewed the English scientific
      literature available on National Library of Medicine (www.pubmed.com) sine 1980
      regarding hypothyroidism, sHT, elderly, L-thyroxine (LT4) therapy, QOL,
      cognition, brain. We supplemented the search with records from personal files,
      textbooks, and relevant articles. The possible link, at molecular level, between
      cognition and thyroid failure was also assessed. Conflicting results on the
      association between sHT and cognitive and health related QOL impairment are still
      present, although the most recent, naturalistic studies did not find any
      significant relationship. Interestingly, a reduction in health related QOL is
      frequently reported in patients with thyroid autoimmune diseases regardless of
      thyroid dysfunction. We also report most significant patents on the topic. 

PMID- 25052002
TI  - Finding of synergistic and cancel effects on the aroxyl radical-scavenging rate
      and suppression of prooxidant effect for coexistence of alpha-tocopherol with
      beta-, gamma-, and delta-tocopherols (or -tocotrienols).
AB  - Measurements of aroxyl radical (ArO*)-scavenging rate constants (k(s)(AOH)) of
      antioxidants (AOHs) [alpha-, beta-, gamma-, and delta-tocopherols (TocHs) and 
      tocotrienols (Toc-3Hs)] were performed in ethanol solution via stopped-flow
      spectrophotometry. k(s)(AOH) values of alpha-, beta-, gamma-, and delta-Toc-3Hs
      showed good agreement with those of the corresponding alpha-, beta-, gamma-, and
      delta- TocHs. k(s)(AOH) values were measured not only for each antioxidant but
      also for mixtures of two antioxidants: (i) alpha-TocH with beta-, gamma-, or
      delta-TocH and (ii) alpha-TocH with alpha-, beta-, gamma-, or delta-Toc-3H. A
      synergistic effect in which the k(s)(AOH) value increases by 12% for gamma-TocH
      (or by 12% for gamma-Toc-3H) was observed for solutions including alpha-TocH and
      gamma-TocH (or gamma-Toc-3H). On the other hand, a cancel effect in which the
      k(s)(AOH) value decreases (a) by 7% for beta-TocH (or 11% for beta-Toc-3H) and
      (b) by 24% for delta-TocH (or 25% for delta-Toc-3H) was observed for solutions
      including two kinds of antioxidants. However, only a synergistic effect may
      function in edible oils, because contents of beta- and delta-TocHs (and beta- and
      delta-Toc-3Hs) are much less than those of alpha- and gamma-TocHs (and alpha- and
      gamma-Toc-3Hs) in many edible oils. UV-vis absorption of alpha-Toc*, which was
      produced by reaction of alpha-TocH with ArO*, decreased remarkably for
      coexistence of alpha-TocH with beta-, gamma-, or delta-TocH (or beta-, gamma-, or
      delta-Toc-3H), indicating that the prooxidant effect of alpha-Toc* is suppressed
      by the coexistence of other TocHs and Toc-3Hs.

PMID- 25052001
TI  - Clinical implications of interferon-gamma genetic and epigenetic variants.
AB  - Interferon-gamma (IFN-gamma) is an integral and critical molecule of the immune
      system, with multiple functions, mostly related to the T helper type 1 (Th1)
      response to infection. It is critical for defence against mycobacterial infection
      and is of increasing interest in defence against fungi. In this article, we
      review the genetic and epigenetic variants affecting IFN-gamma expression and
      investigate its role in disease, with an emphasis on fungal diseases such as
      invasive and chronic pulmonary aspergillosis. Over 347 IFN-gamma gene variants
      have been described, in multiple ethnic populations. Many appear to confer a
      susceptibility to disease, especially tuberculosis (TB) and hepatitis, but also
      some non-infectious conditions such as aplastic anaemia, cervical cancer and
      psoriasis. Several epigenetic modifications are also described, increasing IFN
      gamma expression in Th1 lymphocytes and reducing IFN-gamma expression in Th2
      lymphocytes. Recombinant IFN-gamma administration is licensed for the prophylaxis
      of infection (bacterial and fungal) in patients with the phagocyte functional
      deficiency syndrome chronic granulomatous disease, although the benefits appear
      limited. Interferon-gamma therapy is given to patients with profound defects in
      IFN-gamma and interleukin-12 production and appears to be beneficial for patients
      with invasive aspergillosis and cryptococcal meningitis, but the studies are not
      definitive. A high proportion of patients with chronic pulmonary aspergillosis
      are poor producers of IFN-gamma in response to multiple stimuli and could also
      benefit from IFN-gamma administration. The investigation and management of
      patients with possible or demonstrated IFN-gamma deficiency in adulthood is
      poorly studied and could be greatly enhanced with the integration of genetic
      data. 

PMID- 25052003
TI  - Clofibric acid induces hepatic CYP 2B1/2 via constitutive androstane receptor not
      via peroxisome proliferator activated receptor alpha in rat.
AB  - Peroxisome proliferator activated receptor alpha (PPARalpha) ligands, fibrates
      used to control hyperlipidemia. We demonstrated CYP2B induction by clofibric acid
      (CFA) however, the mechanism was not clear. In this study, HepG2 cells
      transfected with expression plasmid of mouse constitutive androstane receptor
      (CAR) or PPARalpha were treated with CFA, phenobarbital (PB) or TCPOBOP.
      Luciferase assays showed that CFA increased CYP2B1 transcription to the same
      level as PB, or TCPOBOP in HepG2 transfected with mouse CAR But failed to induce
      it in PPARalpha transfected cells. CYP2B expressions were increased with PB or
      CFA in Wistar female rats (having normal levels of CAR) but not in Wistar Kyoto
      female rats (having low levels of CAR). The induction of CYP2B by PB or CFA was
      comparable to nuclear CAR levels. CAR nuclear translocation was induced by CFA in
      both rat strains. This indicates that fibrates can activate CAR and that fibrates
      insulin sensitization effect may occur through CAR, while hypolipidemic effect
      may operate through PPARalpha. 

PMID- 25052004
TI  - Relationship between the public's belief in recovery, level of mental illness
      stigma, and previous contact.
AB  - Disbelief exits that individuals who have a mental health condition are able to
      recover and fully function in life. This study analyzed 1,437 adults from the
      2006 General Social Survey. Structural equation modeling (1) examined the
      relationship between respondents' level of prejudicial attitudes and social
      distance (i.e., stigma) toward individuals who have a mental health condition and
      their belief in the potential of recovery (2) tested whether previous contact
      with an individual who received treatment was a mediator. Findings indicated that
      the belief in recovery led to lower levels of social distance. Prejudicial
      attitudes were found to be a predictor of one's level of social distance.
      Previous contact was not a mediator however; males, minorities and those with
      less education were less likely to have had previous contact. Results indicated a
      need to emphasize the probability of recovering from a mental health condition
      when developing target-specific stigma reducing strategies. 

PMID- 25052006
TI  - Pechini synthesis of lanthanide (Eu3+/Tb3+or Dy3+) ions activated BaGd2O4
      nanostructured phosphors: an approach for tunable emissions.
AB  - Trivalent lanthanide (Eu(3+), Tb(3+) and Dy(3+)) ions activated tunable color
      emitting BaGd2O4 (BG) phosphors were synthesized by a facile Pechini-type sol-gel
      process. The X-ray diffraction pattern confirmed the orthorhombic phase after
      annealing at 1300  degrees C for 5 h. Morphological studies were performed based
      on the analysis of transmission electron microscopy images, which showed needle
      type nanorods. The BG phosphor exhibited good photoluminescence (PL) properties
      in the respective regions when doped with Eu(3+), Tb(3+) and Dy(3+) ions. The
      Eu(3+) co-activated BG:Tb(3+) phosphor yielded tunable emissions including tri
      band established white light emission based on the co-activator concentration and
      excitation wavelength. The energy transfer from Tb(3+) to Eu(3+) ions was
      controlled by selecting a suitable excitation wavelength and the decay
      measurements were carried out for analyzing the energy transfer efficiency. The
      cathodoluminescence properties of these phosphors were almost similar to PL
      properties when doped with individual Eu(3+), Tb(3+), and Dy(3+) ions, but were
      different when co-doped with Eu(3+)/Tb(3+) or Eu(3+)/Dy(3+) ions. In the case of
      Eu(3+)/Tb(3+) doped samples, the energy transfer process occurred unlike the PL
      channel. The calculated Commission International de l'Eclairage chromaticity
      coordinates of individual ion doped BG phosphors confirmed red, green, and white
      emissions and for co-doped samples they showed tunable emission. 

PMID- 25052005
TI  - Hyperhomocysteinemia induced by methionine dietary nutritional overload modulates
      acetylcholinesterase activity in the rat brain.
AB  - Methionine is the only endogenous precursor of homocysteine, sulfur-containing
      amino acid and well known as risk factor for various brain disorders.
      Acetylcholinesterase is a serine protease that rapidly hydrolyzes
      neurotransmitter acetylcholine. It is widely distributed in different brain
      regions. The aim of this study was to elucidate the effects of methionine
      nutritional overload on acetylcholinesterase activity in the rat brain. Males of
      Wistar rats were randomly divided into control and experimental group, fed from
      30th to 60th postnatal day with standard or methionine-enriched diet (double
      content comparing to standard, 7.7 g/kg), respectively. On the 61st postnatal
      day, total homocysteine concentration was determined and showed that animals fed
      with methionine-enriched diet had significantly higher serum total homocysteine
      concentrations comparing to control rats (p < 0.01). Acetylcholinesterase
      activity has been determined spectrophotometrically in homogenates of the
      cerebral cortex, hippocampus, thalamus, and nc. caudatus. Acetylcholinesterase
      activity showed tendency to decrease in all examined brain structures in
      experimental comparing to control rats, while statistical significance of this
      reduction was achieved in the cerebral cortex (p < 0.05). Brain slices were
      stained with haematoxylin and eosin (H&E) and observed under light microscopy.
      Histological analysis of H&E-stained brain slices showed that there were no
      changes in the brain tissue of rats which were on methionine-enriched diet
      compared to control rats. Results of this study showed selective vulnerability of
      different brain regions on reduction of acetylcholinesterase activity induced by
      methionine-enriched diet and consecutive hyperhomocysteinemia.

PMID- 25052007
TI  - Aberrant DNA methylation of blood in schizophrenia by adjusting for estimated
      cellular proportions.
AB  - DNA methylation, which is the transference of a methyl group to the 5'-carbon
      position of the cytosine in a CpG dinucleotide, is one of the major mechanisms of
      epigenetic modifications. A number of studies have demonstrated altered DNA
      methylation of peripheral blood cells in schizophrenia (SCZ) in previous studies.
      However, most of these studies have been limited to the analysis of the CpG sites
      in CpG islands in gene promoter regions, and cell-type proportions of peripheral
      leukocytes, which may be one of the potential confounding factors for DNA
      methylation, have not been adjusted in these studies. In this study, we performed
      a genome-wide DNA methylation profiling of the peripheral leukocytes from
      patients with SCZ and from non-psychiatric controls (N = 105; 63 SCZ and 42
      control subjects) using a quantitative high-resolution DNA methylation microarray
      which covered across the whole gene region (485,764 CpG dinucleotides). In the
      DNA methylation data analysis, we first estimated the cell-type proportions of
      each sample with a published algorithm. Next, we performed a surrogate variable
      analysis to identify potential confounding factors in our microarray data.
      Finally, we conducted a multiple linear regression analysis in consideration of
      these factors, including estimated cell-type proportions, and identified aberrant
      DNA methylation in SCZ at 2,552 CpG loci at a 5% false discovery rate correction.
      Our results suggest that altered DNA methylation may be involved in the
      pathophysiology of SCZ, and cell heterogeneity adjustments may be necessary for
      DNA methylation analysis.

PMID- 25052008
TI  - Global temperature constraints on Aedes aegypti and Ae. albopictus persistence
      and competence for dengue virus transmission.
AB  - BACKGROUND: Dengue is a disease that has undergone significant expansion over the
      past hundred years. Understanding what factors limit the distribution of
      transmission can be used to predict current and future limits to further dengue
      expansion. While not the only factor, temperature plays an important role in
      defining these limits. Previous attempts to analyse the effect of temperature on
      the geographic distribution of dengue have not considered its dynamic intra
      annual and diurnal change and its cumulative effects on mosquito and virus
      populations. METHODS: Here we expand an existing modelling framework with new
      temperature-based relationships to model an index proportional to the basic
      reproductive number of the dengue virus. This model framework is combined with
      high spatial and temporal resolution global temperature data to model the effects
      of temperature on Aedes aegypti and Ae. albopictus persistence and competence for
      dengue virus transmission. RESULTS: Our model predicted areas where temperature
      is not expected to permit transmission and/or Aedes persistence throughout the
      year. By reanalysing existing experimental data our analysis indicates that Ae.
      albopictus, often considered a minor vector of dengue, has comparable rates of
      virus dissemination to its primary vector, Ae. aegypti, and when the longer
      lifespan of Ae. albopictus is considered its competence for dengue virus
      transmission far exceeds that of Ae. aegypti. CONCLUSIONS: These results can be
      used to analyse the effects of temperature and other contributing factors on the
      expansion of dengue or its Aedes vectors. Our finding that Ae. albopictus has a
      greater capacity for dengue transmission than Ae. aegypti is contrary to current
      explanations for the comparative rarity of dengue transmission in established Ae.
      albopictus populations. This suggests that the limited capacity of Ae. albopictus
      to transmit DENV is more dependent on its ecology than vector competence. The
      recommendations, which we explicitly outlined here, point to clear targets for
      entomological investigation.

PMID- 25052009
TI  - The role of CD4(+) T cells in BKV-specific T cell immunity.
AB  - Reactivation of polyomavirus BK (BKV) infection represents a severe complication
      in kidney transplant (KTX) patients. We previously reported an association
      between a declining BK viral load and the reconstitution of CD4(+) T cell BKV
      specific immunity in patients following kidney transplantation. However, the
      specific contribution of CD4(+) T cells in the regulation of BKV-replication is
      unknown. Nevertheless, in vitro enrichment of BKV-specific T cells and subsequent
      adoptive T cell transfer may improve the restoration of immune competence in KTX
      patients with BKV infection. To date, strategies to capture human BKV-specific T
      cells with the ensuing expansion to clinically useful numbers are lacking. Here,
      we demonstrated a comprehensive flow cytometric analysis of the BKV-specific T
      cell response that permits access to the majority of T cells specific for
      immunodominant BKV antigens. A full-spectrum evaluation of the BKV-specific T
      cell response was performed by stimulating peripheral blood mononuclear cells
      (PBMC) with a mixture of BKV immunodominant peptide pools at varying
      concentrations and measuring activation marker expression and cytokine secretion.
      We also examined the effects of co-stimulation and PBMC resting time prior to
      activation. We defined the narrow range of stimulation conditions that permit the
      capture and expansion of functional BKV-specific T cell lines. The generated BKV
      specific T cell lines showed the highest specificity and functionality when the T
      cells were captured according to IFNgamma-secretion. This study highlights the
      multifunctional and cytolytic BKV-specific CD4(+) T cells as a dominant
      population within the generated T cell product. This method offers a novel
      approach for the generation of BKV-specific T cell lines for adoptive
      immunotherapy and underscores the critical role of CD4(+) T cells in the
      clearance of BKV. 

PMID- 25052010
TI  - Defining the optimal cardiac troponin T threshold for predicting death caused by
      periprocedural myocardial infarction after percutaneous coronary intervention.
AB  - BACKGROUND: There is controversy about the diagnostic and prognostic significance
      of percutaneous coronary intervention-related myocardial infarction, especially
      with the use of cardiac troponin T (cTnT). This analysis was designed to address
      the question of the presence and the level of a prognostic cTnT threshold.
      METHODS AND RESULTS: We evaluated 5268 consecutive patients who underwent
      nonemergent percutaneous coronary intervention between 2000 and 2009 with a
      preprocedural cTnT level below the upper limit of normal (ULN, <=0.01 ng/mL).
      Postprocedural cTnT and creatine kinase-MB mass levels (ULN, 6.7 ng/mL in men and
      3.8 ng/mL in women) were found to be associated with 3-month mortality in Cox
      proportional hazard models (hazard ratio per doubling of cTnT, 1.24; 95%
      confidence interval, 1.08-1.43; P=0.003 and hazard ratio per doubling of creatine
      kinase-MB, 1.30; 95% confidence interval, 1.05-1.60; P=0.018), adjusted for the
      Mayo Clinic risk scores for in-hospital and postdischarge mortality. The optimal
      prognostic threshold for 3-month mortality was 25* ULN for cTnT (hazard ratio,
      4.53; 99% confidence interval, 1.59-12.9; P<0.001), which provided similar
      information as a value of 5* ULN for creatine kinase-MB (hazard ratio, 4.31; 99%
      confidence interval, 1.27-14.6; P=0.002). The cumulative mortality rate was 0.6%
      at 91 days. CONCLUSIONS: A significant association of postpercutaneous coronary
      intervention cardiac biomarker elevation with a small number of postpercutaneous
      coronary intervention outcomes was noted for the early (first 91 days) follow-up
      period with an identifiable optimal threshold of 25* ULN (0.25, ng/mL) for cTnT,
      which provided similar early outcome information as a cutoff of 5* ULN for
      creatine kinase-MB.

PMID- 25052011
TI  - ESHRE Task Force on Ethics and Law 23: medically assisted reproduction in
      singles, lesbian and gay couples, and transsexual people?.
AB  - This Task Force document discusses ethical issues arising with requests for
      medically assisted reproduction from people in what may be called 'non-standard'
      situations and relationships. The document stresses that categorically denying
      access to any of these groups cannot be reconciled with a human rights
      perspective. If there are concerns about the implications of assisted
      reproduction on the wellbeing of any of the persons involved, including the
      future child, a surrogate mother or the applicants themselves, these concerns
      have to be considered in the light of the available scientific evidence. When
      doing so it is important to avoid the use of double standards. More research is
      needed into the psychosocial implications of raising children in non-standard
      situations, especially with regard to single women, male homosexual couples and
      transsexual people. 

PMID- 25052012
TI  - The value of adding transcutaneous neuromuscular electrical stimulation
      (VitalStim) to traditional therapy for post-stroke dysphagia: a randomized
      controlled trial.
AB  - BACKGROUND: Dysphagia is not uncommon after stroke. Dysphagia may delay the
      functional recovery and substantially affects the quality of life after stroke,
      mainly if lest untreated. To detect and treat dysphagia as early as possible is
      critical for patients' recovery after stroke. Electrical stimulation has been
      reported as a treatment for pharyngeal dysphagia in recent studies, but the
      therapeutic effects of neuromuscular electrical stimulation (VitalStim(r))
      therapy lacks convincing supporting evidence, needs further clinical
      investigation. AIM: To investigate the effects of neuromuscular electrical
      stimulation (VitalStim(r)) and traditional swallowing therapy on recovery of
      swallowing difficulties after stroke. DESIGN: Randomized controlled trial.
      SETTING: University hospital. POPULATION: 135 stroke patients who had a diagnosis
      of dysphagia at the age between 50-80. METHODS: 135 subjects were randomly
      divided into three groups: traditional swallowing therapy (N. = 45), VitalStim(r)
      therapy (N. = 45), and VitalStim(r) therapy plus traditional swallowing therapy
      (N. = 45). The traditional swallowing therapy included basic training and direct
      food intake training. Electrical stimulation was applied by an occupational
      therapist, using a modified hand-held battery-powered electrical stimulator
      (VitalStim(r) Dual Channel Unit and electrodes, Chattanooga Group, Hixson, TN,
      USA). Surface electromyography (sEMG), the Standardized Swallowing Assessment
      (SSA), Videofluoroscopic Swallowing Study (VFSS) and visual analog scale (VAS)
      were used to assess swallowing function before and 4 weeks after the treatment.
      RESULTS: The study included 118 subjects with dysphagia, 40 in the traditional
      swallowing therapy group and VitalStim(r) therapy group, 38 in the VitalStim and
      traditional swallowing therapy group. There were significant differences in sEMG
      value, SSA and VFSS scores in each group after the treatment (P < 0.001). After 4
      week treatment, sEMG value (917.1 +/- 91.2), SSA value (21.8 +/- 3.5), oral
      transit time (0.4 +/- 0.1) and pharyngeal transit time (0.8 +/- 0.1) were
      significantly improved in the VitalStim(r) and traditional swallowing therapy
      group than the other two groups (P < 0.001). CONCLUSION: Data suggest that
      VitalStim(r) therapy coupled with traditional swallowing therapy may be
      beneficial for post-stroke dysphagia. CLINICAL REHABILITATION IMPACT:
      VitalStim(r) therapy coupled with traditional swallowing therapy can improve
      functional recovery for post-stroke dysphagia.

PMID- 25052013
TI  - Gait analysis contribution to problems identification and surgical planning in CP
      patients: an agreement study.
AB  - BACKGROUND: Previous studies have demonstrated that the use of gait analysis (GA)
      modifies decision making and changes planned surgical treatment, confirming some
      clinical indications or defining alternative choices, excluding or delaying
      already planned surgery in children with cerebral palsy (CP). AIM: To assess the
      difference in defining functional problems and treatment relevance using clinical
      assessment or gait analysis in CP children. DESIGN: The study has been designed
      for assessing the rate of agreement on muscle-skeletal diagnosis, and on surgical
      recommendations in diplegic CP patients, when decided by two different blinded
      clinicians based on a) clinical assessment, and b) GA in addition to clinical
      assessment. POPULATION: Twenty-five diplegic children who have been evaluated by
      GA before surgery and at a follow up of at least 6 months. Methods. Two separate
      lists of problems and consequent surgical interventions were outlined for all the
      patients by two blinded experts from clinical and GA assessment. The two sets of
      nominal-scale ratings for all patients of the two groups were statistically
      evaluated for agreement. RESULTS: A fair and a slight agreement was found
      respectively between the two sets of problems and the two sets of surgical plans.
      Main differences in problems identified were relative to the presence of
      generalized spasticity and bony deformities as detected by means of GA instead of
      local problems and soft tissues spasticity/retraction clinically identified. As a
      consequence, by means of GA, surgery was indicated only in 65% of patients.
      CONCLUSION: The availability of a GA laboratory helps in diagnostic reasoning in
      CP children indicated for surgery. Low agreement found appears to be a result of
      a different clinical approach of the surgeons. CLINICAL REHABILITATION IMPACT:
      The use of GA in the analysis of motor problems in CP children provides a basis
      for an objective reasoning for clinical decision making and for assessing
      functional outcome. Further efforts are required to build a body of knowledge
      about a consensus on the identification of walking problems in CP children.

PMID- 25052014
TI  - Developing a monitoring and evaluation framework to integrate and formalize the
      informal waste and recycling sector: the case of the Philippine National
      Framework Plan.
AB  - The Philippines has been making inroads in solid waste management with the
      enactment and implementation of the Republic Act 9003 or the Ecological Waste
      Management Act of 2000. Said legislation has had tremendous influence in terms of
      how the national and local government units confront the challenges of waste
      management in urban and rural areas using the reduce, reuse, recycle and recovery
      framework or 4Rs. One of the sectors needing assistance is the informal waste
      sector whose aspiration is legal recognition of their rank and integration of
      their waste recovery activities in mainstream waste management. To realize this,
      the Philippine National Solid Waste Management Commission initiated the
      formulation of the National Framework Plan for the Informal Waste Sector, which
      stipulates approaches, strategies and methodologies to concretely involve the
      said sector in different spheres of local waste management, such as collection,
      recycling and disposal. What needs to be fleshed out is the monitoring and
      evaluation component in order to gauge qualitative and quantitative achievements
      vis-a-vis the Framework Plan. In the process of providing an enabling environment
      for the informal waste sector, progress has to be monitored and verified
      qualitatively and quantitatively and measured against activities, outputs,
      objectives and goals. Using the Framework Plan as the reference, this article
      developed monitoring and evaluation indicators using the logical framework
      approach in project management. The primary objective is to institutionalize
      monitoring and evaluation, not just in informal waste sector plans, but in any
      waste management initiatives to ensure that envisaged goals are achieved. 

PMID- 25052016
TI  - Forest owners' perceptions of ecotourism: Integrating community values and forest
      conservation.
AB  - The use of forest land for ecotourism has been well accepted due to its ability
      to provide income to local people and to conserve the forest. Preparing the
      forest with infrastructure to attract and educate visitors has been reported of
      importance. This study applied Q methodology in a small rural community of the
      State of Puebla, Mexico, to reveal forest owners' perceptions to build
      infrastructure in their forest as part of their ecotourism project. It also
      discloses forest owners' underlying motives to use their forest for ecotourism.
      Ecotourism is perceived as a complementary activity to farming that would allow
      women to be involved in community development. Low impact infrastructure is
      desired due to forest owners' perception to preserve the forest for the overall
      community well-being. 

PMID- 25052015
TI  - Elastic, conductive, polymeric hydrogels and sponges.
AB  - As a result of inherent rigidity of the conjugated macromolecular chains resulted
      from the delocalized pi-electron system along the polymer backbone, it has been a
      huge challenge to make conducting polymer hydrogels elastic by far. Herein
      elastic and conductive polypyrrole hydrogels with only conducting polymer as the
      continuous phase have been simply synthesized in the indispensable conditions of
      1) mixed solvent, 2) deficient oxidant, and 3) monthly secondary growth. The
      elastic mechanism and oxidative polymerization mechanism on the resulting PPy
      hydrogels have been discussed. The resulting hydrogels show some novel
      properties, e.g., shape memory elasticity, fast functionalization with various
      guest objects, and fast removal of organic infectants from aqueous solutions, all
      of which cannot be observed from traditional non-elastic conducting polymer
      counterparts. What's more, light-weight, elastic, and conductive organic sponges
      with excellent stress-sensing behavior have been successfully achieved via using
      the resulting polypyrrole hydrogels as precursors. 

PMID- 25052017
TI  - Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate
      pool.
AB  - The occurrence of modified bases in DNA is attributed to some major factors:
      incorporation of altered nucleotide building blocks and chemical reactions or
      radiation effects on bases within the DNA structure. Several enzyme families are
      involved in preventing the incorporation of noncanonical bases playing a
      'sanitizing' role. The catalytic mechanism of action of these enzymes has been
      revealed for a number of representatives in clear structural and kinetic detail.
      In this review, we focus in detail on those examples where clear evidence has
      been produced using high-resolution structural studies. Comparing the protein
      fold and architecture of the enzyme active sites, two main classes of sanitizing
      deoxyribonucleoside triphosphate pyrophosphatases can be assigned that are
      distinguished by the site of nucleophilic attack. In enzymes associated with
      attack at the alpha-phosphorus, it is shown that coordination of the gamma
      phosphate group is also ensured by multiple interactions. By contrast, enzymes
      catalyzing attack at the beta-phosphorus atom mainly coordinate the alpha- and
      the beta-phosphate only. Characteristic differences are also observed with
      respect to the role of the metal ion cofactor (Mg(2+) ) and the coordination of
      nucleophilic water. Using different catalytic mechanisms embedded in different
      protein folds, these enzymes present a clear example of convergent evolution. 

PMID- 25052018
TI  - Optimal back-extrapolation method for estimating plasma volume in humans using
      the indocyanine green dilution method.
AB  - BACKGROUND: The indocyanine green dilution method is one of the methods available
      to estimate plasma volume, although some researchers have questioned the accuracy
      of this method. METHODS: We developed a new, physiologically based mathematical
      model of indocyanine green kinetics that more accurately represents indocyanine
      green kinetics during the first few minutes postinjection than what is assumed
      when using the traditional mono-exponential back-extrapolation method. The
      mathematical model is used to develop an optimal back-extrapolation method for
      estimating plasma volume based on simulated indocyanine green kinetics obtained
      from the physiological model. RESULTS: Results from a clinical study using the
      indocyanine green dilution method in 36 subjects with type 2 diabetes indicate
      that the estimated plasma volumes are considerably lower when using the
      traditional back-extrapolation method than when using the proposed back
      extrapolation method (mean (standard deviation) plasma volume = 26.8 (5.4) mL/kg
      for the traditional method vs 35.1 (7.0) mL/kg for the proposed method). The
      results obtained using the proposed method are more consistent with previously
      reported plasma volume values. CONCLUSIONS: Based on the more physiological
      representation of indocyanine green kinetics and greater consistency with
      previously reported plasma volume values, the new back-extrapolation method is
      proposed for use when estimating plasma volume using the indocyanine green
      dilution method.

PMID- 25052019
TI  - Musculoskeletal: what is different in children? Jumped off of a merry-go-round:
      immediate crying and cannot walk on the left leg.

PMID- 25052020
TI  - An innovative interactive medical student induction programme in paediatrics.

PMID- 25052021
TI  - Assessing Symbiodinium diversity in scleractinian corals via next-generation
      sequencing-based genotyping of the ITS2 rDNA region.
AB  - The persistence of coral reef ecosystems relies on the symbiotic relationship
      between scleractinian corals and intracellular, photosynthetic dinoflagellates in
      the genus Symbiodinium. Genetic evidence indicates that these symbionts are
      biologically diverse and exhibit discrete patterns of environmental and host
      distribution. This makes the assessment of Symbiodinium diversity critical to
      understanding the symbiosis ecology of corals. Here, we applied pyrosequencing to
      the elucidation of Symbiodinium diversity via analysis of the internal
      transcribed spacer 2 (ITS2) region, a multicopy genetic marker commonly used to
      analyse Symbiodinium diversity. Replicated data generated from isoclonal
      Symbiodinium cultures showed that all genomes contained numerous, yet mostly
      rare, ITS2 sequence variants. Pyrosequencing data were consistent with more
      traditional denaturing gradient gel electrophoresis (DGGE) approaches to the
      screening of ITS2 PCR amplifications, where the most common sequences appeared as
      the most intense bands. Further, we developed an operational taxonomic unit (OTU)
      based pipeline for Symbiodinium ITS2 diversity typing to provisionally resolve
      ecologically discrete entities from intragenomic variation. A genetic distance
      cut-off of 0.03 collapsed intragenomic ITS2 variants of isoclonal cultures into
      single OTUs. When applied to the analysis of field-collected coral samples, our
      analyses confirm that much of the commonly observed Symbiodinium ITS2 diversity
      can be attributed to intragenomic variation. We conclude that by analysing
      Symbiodinium populations in an OTU-based framework, we can improve objectivity,
      comparability and simplicity when assessing ITS2 diversity in field-based
      studies. 

PMID- 25052022
TI  - Arthrobacter enclensis sp. nov., isolated from sediment sample.
AB  - A novel bacterial strain designated as NIO-1008(T) was isolated from marine
      sediments sample in Chorao Island India. Cells of the strains were gram positive
      and non-motile, displayed a rod-coccus life cycle and formed cream to light grey
      colonies on nutrient agar. Strain NIO-1008(T) had the chemotaxonomic markers that
      were consistent for classification in the genus Arthrobacter, i.e. MK-9(H2) (50.3
      %), as the major menaquinone, and the minor amount of MK-7 (H2-27.5 %), MK-8 (H4
      11.6 %) and MK-8 (H2-10.4 %). anteiso-C15:0, iso-C15:0, iso-C16:0 and C15:0 were
      the predominant fatty acids. Galactose, glucose and rhamnose are the cell-wall
      sugars, and DNA G+C content was 61.3 mol%. Phylogenetic analysis, based on 16S
      rRNA gene sequencing, showed that the strains were most similar to Arthrobacter
      equi IMMIB L-1606(T), Arthrobacter chlorophenolicus DSM 12829(T), Arthrobacter
      defluvii KCTC 19209(T) and Arthrobacter niigatensis CCTCC AB 206012(T) with 98.5,
      98.4, 98.0 and 97.8 %, respectively, and formed a separate lineage. Combined
      phenotypic data and DNA-DNA hybridization data supported the conclusion that
      strains NIO-1008(T) represent a novel species within the genus Arthrobacter, for
      which the name Arthrobacter enclensis sp. nov., is proposed. The type strain is
      NIO-1008(T) = (NCIM 5488(T) = DSM 25279(T)). 

PMID- 25052023
TI  - Mutualist-mediated effects on species' range limits across large geographic
      scales.
AB  - Understanding the processes determining species range limits is central to
      predicting species distributions under climate change. Projected future ranges
      are extrapolated from distribution models based on climate layers, and few models
      incorporate the effects of biotic interactions on species' distributions. Here,
      we show that a positive species interaction ameliorates abiotic stress, and has a
      profound effect on a species' range limits. Combining field surveys of 92
      populations, 10 common garden experiments throughout the range, species
      distribution models and greenhouse experiments, we show that mutualistic fungal
      endophytes ameliorate drought stress and broaden the geographic range of their
      native grass host Bromus laevipes by thousands of square kilometres (~ 20%
      larger) into drier habitats. Range differentiation between fungal-associated and
      fungal-free grasses was comparable to species-level range divergence of
      congeners, indicating large impacts on range limits. Positive biotic interactions
      may be underappreciated in determining species' ranges and species' responses to
      future climates across large geographic scales.

PMID- 25052025
TI  - Overview of the relevant literature on the possible role of acupuncture in
      treating male sexual dysfunction.
AB  - OBJECTIVE: To systematically review scientific reports on the effectiveness of
      acupuncture to treat male sexual dysfunction. METHODS: The Medline database was
      searched for published clinical trials of acupuncture for erectile dysfunction
      (ED) and premature ejaculation (PE) with English abstracts. Risk of bias was
      assessed for randomised controlled trials (RCTs). RESULTS: Seven studies on two
      conditions of male sexual dysfunction met the inclusion criteria. Three out of
      four RCTs were patient-blinded, but all had a high risk of bias. Three suggested
      that acupuncture has a therapeutic effect as compared with sham acupuncture.
      Comparisons with paroxetine were inconsistent. Other uncontrolled studies and
      case series suggested satisfactory improvements of ED and PE after acupuncture.
      CONCLUSIONS: Acupuncture appears to have promise for treating male sexual
      dysfunction, but in view of the small number of studies and their variable
      quality, doubts remain about its effectiveness. Further studies are justified.

PMID- 25052024
TI  - Systematic permutation testing in GWAS pathway analyses: identification of
      genetic networks in dilated cardiomyopathy and ulcerative colitis.
AB  - BACKGROUND: Genome wide association studies (GWAS) are applied to identify
      genetic loci, which are associated with complex traits and human diseases.
      Analogous to the evolution of gene expression analyses, pathway analyses have
      emerged as important tools to uncover functional networks of genome-wide
      association data. Usually, pathway analyses combine statistical methods with a
      priori available biological knowledge. To determine significance thresholds for
      associated pathways, correction for multiple testing and over-representation
      permutation testing is applied. RESULTS: We systematically investigated the
      impact of three different permutation test approaches for over-representation
      analysis to detect false positive pathway candidates and evaluate them on genome
      wide association data of Dilated Cardiomyopathy (DCM) and Ulcerative Colitis
      (UC). Our results provide evidence that the gold standard - permuting the case
      control status - effectively improves specificity of GWAS pathway analysis.
      Although permutation of SNPs does not maintain linkage disequilibrium (LD), these
      permutations represent an alternative for GWAS data when case-control
      permutations are not possible. Gene permutations, however, did not add
      significantly to the specificity. Finally, we provide estimates on the required
      number of permutations for the investigated approaches. CONCLUSIONS: To discover
      potential false positive functional pathway candidates and to support the results
      from standard statistical tests such as the Hypergeometric test, permutation
      tests of case control data should be carried out. The most reasonable alternative
      was case-control permutation, if this is not possible, SNP permutations may be
      carried out. Our study also demonstrates that significance values converge
      rapidly with an increasing number of permutations. By applying the described
      statistical framework we were able to discover axon guidance, focal adhesion and
      calcium signaling as important DCM-related pathways and Intestinal immune network
      for IgA production as most significant UC pathway.

PMID- 25052026
TI  - The genomic and seroprevalence of human bocavirus in healthy Chinese plasma
      donors and plasma derivatives.
AB  - BACKGROUND: Human bocavirus (HBoV) is a novel parvovirus identified in 2005. It
      has mostly been detected in respiratory and enteric infections and has not been
      studied large scale in blood products in relation to transfusion. STUDY DESIGN
      AND METHODS: An in-house quantitative polymerase chain reaction (Q-PCR) was
      developed to test HBoV DNA in plasma and plasma derivatives. Plasma samples (n =
      6096) collected from healthy donors, 241 plasma pools, and 326 plasma derivatives
      were screened for HBoV DNA by Q-PCR. Positive samples were confirmed by nested
      PCR and further amplified for sequence analysis and phylogenetic studies. The
      prevalence of immunoglobulin (Ig)G and IgM specific to HBoV structural proteins
      was measured by enzyme-linked immunosorbent assay in 209 samples grouped
      according to virus load (Group 1, HBoV DNA >10(4) copies/mL; Group 2, HBoV DNA >5
      * 10(2) copies/mL but below 10(4) copies/mL; Group 3,HBoV DNA negative). RESULTS:
      The genomic prevalence of HBoV in the plasma donors was 9.06%, ranging from 5.01
      * 10(2) to 3.02 * 10(6) copies/mL. HBoV-specific IgG and IgM were detected at
      20.00 and 7.50% in Group 1, at 20.29 and 2.90% in Group 2, and at 13.00 and 4.0%
      in Group 3, respectively. Phylogenetic analyses proved that HBoV Genotype 1 was
      the prevalent genotype in Chinese plasma donors. CONCLUSION: Low levels of HBoV
      DNA were detectable at high prevalence in Chinese plasma donors and plasma
      derivatives. Further study is needed to determine whether HBoV screening is
      necessary.

PMID- 25052027
TI  - Imagine: a coordinated federated approach that supports translational science and
      improves health.

PMID- 25052028
TI  - Identification and characterization of promoters specifically and strongly
      expressed in maize embryos.
AB  - The use of maize seeds as bioreactors has several advantages for the production
      of recombinant proteins in plant biotechnology, but available embryo-specific and
      strong promoters are limited. Here, we describe a genome-scale microarray-based
      approach to identify embryo-specifically and strongly expressed genes and their
      promoters in maize. We identified 28 embryo-preferred and abundantly expressed
      genes based on our microarray data. These embryo-preferred genes were further
      analysed using the UniGene database and by quantitative reverse transcriptase-PCR
      leading to the identification of seven genes (Zm.2098, Zm.13387, Zm.66589,
      Zm.85502, Zm.68129, Zm.3896 and Zm.2941) as embryo-specific genes with higher
      expression levels relative to maize globulin-1. The putative promoters of five
      embryo-specific genes (Zm.13387, Zm.66589, Zm.85502, Zm.3896 and Zm.2941) were
      isolated and all exhibited strong promoter activities when transiently expressed
      in maize embryos of 20 DAP. The embryo specificity and expression levels of the
      promoters of four genes (Zm.13387, Zm.85502, Zm.3896 and Zm.2941) were further
      examined in transgenic maize plants, revealing that they are strong promoters in
      embryos of all four developmental stages tested compared with reference globulin
      1 promoter. Moreover, Zm.2941 and Zm.3896 promoters are stringently embryo
      specific promoters, while Zm.85502 promoter is basically embryo specific yet
      wounding inducible in non-seed tissues, and Zm.13387 promoter is developmentally
      expressed in both embryo and aleurone with wounding-induced activity in non-seed
      tissues. Our study provides novel embryo-specific and strong promoters that are
      suitable for production of high-level recombinant proteins in maize embryos. 

PMID- 25052029
TI  - Effects of neuromuscular deprogramming on the head position.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of the
      neuromuscular deprogramming of the mandible on the craniocervical position.
      METHODS: Participants (n=65) were separated into two groups: 25 untreated
      controls (10 men and 15 women) and 40 patients (17 men and 23 women) and
      underwent neuromuscular deprogramming with upper occlusal splints for an average
      of 6 months and 7 days, before orthodontic treatment. Lateral cephalograms were
      obtained from each subject in the natural head position (NHP), before and after
      neuromuscular deprogramming. Craniocervical cephalometric analysis was performed
      to evaluate craniovertical (NSL/VER), craniocervical (OPT/NSL and CVT/NSL), and
      cervicohorizontal (OPT/HOR and CVT/HOR) angulation, and the angle of the cervical
      curvature (OPT/CVT). RESULTS: After neuromuscular deprogramming, significant
      changes in three angles--NSL/VER (P<0.001), OPT/NSL (P<0.001) and CVT/NSL
      (P<0.001)--were found between the two groups. For the cervical spine position, no
      significant changes were observed. CONCLUSION: The results indicate that
      neuromuscular deprogramming using occlusal splint causes significant extension of
      the head.

PMID- 25052030
TI  - 3D geometry analysis of the medial meniscus--a statistical shape modeling
      approach.
AB  - The geometry-dependent functioning of the meniscus indicates that detailed
      knowledge on 3D meniscus geometry and its inter-subject variation is essential to
      design well functioning anatomically shaped meniscus replacements. Therefore, the
      aim of this study was to quantify 3D meniscus geometry and to determine whether
      variation in medial meniscus geometry is size- or shape-driven. Also we performed
      a cluster analysis to identify distinct morphological groups of medial menisci
      and assessed whether meniscal geometry is gender-dependent. A statistical shape
      model was created, containing the meniscus geometries of 35 subjects (20 females,
      15 males) that were obtained from MR images. A principal component analysis was
      performed to determine the most important modes of geometry variation and the
      characteristic changes per principal component were evaluated. Each meniscus from
      the original dataset was then reconstructed as a linear combination of principal
      components. This allowed the comparison of male and female menisci, and a cluster
      analysis to determine distinct morphological meniscus groups. Of the variation in
      medial meniscus geometry, 53.8% was found to be due to primarily size-related
      differences and 29.6% due to shape differences. Shape changes were most prominent
      in the cross-sectional plane, rather than in the transverse plane. Significant
      differences between male and female menisci were only found for principal
      component 1, which predominantly reflected size differences. The cluster analysis
      resulted in four clusters, yet these clusters represented two statistically
      different meniscal shapes, as differences between cluster 1, 2 and 4 were only
      present for principal component 1. This study illustrates that differences in
      meniscal geometry cannot be explained by scaling only, but that different
      meniscal shapes can be distinguished. Functional analysis, e.g. through finite
      element modeling, is required to assess whether these distinct shapes actually
      influence the biomechanical performance of the meniscus.

PMID- 25052032
TI  - Highly sensitive detection of zearalenone in feed samples using competitive
      surface-enhanced Raman scattering immunoassay.
AB  - Accurate and quantitative analysis of mycotoxin (such as zearalenone) is
      particularly imperative in the field of food safety and animal husbandry. Here,
      we develop a sensitive and specific method for zearalenone detection using
      competitive surface-enhanced Raman scattering (SERS) immunoassay. In this assay,
      a functional gold nanoparticle was labeled with the Raman reporter and the
      zearalenone antibody, and a modified substrate was assembled with the zearalenone
      bovine serum albumin. With the addition of free zearalenone, the competitive
      immune reaction between free zearalenone and zearalenone-bovine serum albumin was
      initiated for binding with zearalenone antibody labeled on gold nanoparticle,
      resulting in the change of SERS signal intensity. The proposed method exhibits
      high sensitivity with a detection limit of 1 pg/mL and a wide dynamic range from
      1 to 1000 pg/mL. Furthermore, this method can be further applied to analyze the
      multiple natural feed samples contaminated with zearalenone, holding great
      potential for real sample detection. 

PMID- 25052033
TI  - Health effects of Vaccinium myrtillus L.: evaluation of efficacy and
      technological strategies for preservation of active ingredients.
AB  - Bilberries are a rich dietary source of various phytonutrients, including
      anthocyanins which contribute greatly to their antioxidant capacity and have
      demonstrated a broad spectrum of biomedical functions. These include protection
      against cardiovascular disorders, age-induced oxidative stress, inflammatory
      responses and several degenerative diseases. Berry anthocyanins also improve
      neuronal and cognitive brain functions, ocular health as well as protecting
      genomic DNA integrity. In recent years, sales of many dietary
      supplements/pharmaceutical products containing anthocyanins in various dosages
      and formulations have been made by advertising their wide range of beneficial
      effects. However, there is a heightened risk of distributing deteriorated
      formulations to consumers due to lax regulations, in particular those applicable
      to phytochemical characterization and extract standardization, and in terms of
      quality regarding the stability of anthocyanins. Anthocyanin pigments readily
      degrade during industrial processing and this can have a dramatic impact on color
      quality and may also affect nutritional/pharmaceutical properties. This review
      aims to summarize the main health effects of bilberry extract used in several
      food supplements/pharmaceutical formulations focusing on some important aspects
      of anthocyanin degradation during processing and storage. It will also describe
      the main technological strategies which can give active ingredients greater
      stability, solubility and dispersibility in order to enhance formulation quality
      which is of great interest to the consumer and industry due to its direct and
      indirect impact on consumer health. 

PMID- 25052034
TI  - Recent updates on glucokinase activators for the treatment of type 2 diabetes
      mellitus.
AB  - Glucose-phosphorylating enzyme, glucokinase (GK) plays a major role in glucose
      homeostasis primarily through its regulatory actions in pancreatic beta-cells and
      liver hepatocytes. Conversion of glucose to glucose-6-phosphate by GK promotes
      glycogen synthesis in liver hepatocytes, and insulin release in the pancreatic
      beta-cells. Small molecules called glucokinase activators (GKAs) which bind to an
      allosteric activator site of the GK enzyme have indeed been discovered and
      developed, and thus hold great promise as new, effective and safe antidiabetic
      agents. GKAs enhance the catalytic activity of GK and promising clinical trials
      in humans demonstrated that they are highly useful in the treatment of type 2
      diabetes mellitus. Most of the reported GKAs include amide derivatives like
      benzamides, acrylamides, carboxamides, acetamides and acrylamides. Examples
      include Piragliatin, AZD1656, AZD6370, R1440 GKA2, GKA 50, YH GKA, PSN 010, and
      LY2121260. Recent findings on GKAs including lead compounds and overview of
      current hypothesis on mechanism of GK activation along with summary of the
      recently published patents as well as the GKAs of natural origin are reported in
      the present review. 

PMID- 25052035
TI  - Knockdown of the NHR-8 nuclear receptor enhanced sensitivity to the lipid
      reducing activity of alkaloids in Caenorhabditis elegans.
AB  - Caenorhabditis elegans is a versatile, whole-organism model for bioactivity
      screening. However, this worm has extensive defensive mechanisms against
      xenobiotics which limit its use for screening of pharmacologically active
      compounds. In this study, we report that knockdown of nhr-8, a gene involved in
      the xenobiotic response, increased the worm's sensitivity to the lipid-reducing
      effects of some isoquinoline alkaloids, especially berberine. On the other hand,
      crude extract of rhizome and cultured cells showed enhanced biological activity
      compared to the pure alkaloids in wild type worm, but this enhanced activity was
      not detected in nhr-8 RNAi worm, suggesting that some components in cell extracts
      might interfere with the defense response in this worm. The possibility of using
      C. elegans as a model for screening bioactive chemicals is discussed.

PMID- 25052036
TI  - A meta-analysis and meta-regression of outcomes including biliary complications
      in donation after cardiac death liver transplantation.
AB  - Donation after cardiac death (DCD) liver transplantation is increasingly common
      but concerns exist over the development of biliary complications and ischemic
      cholangiopathy (IC). This study aimed to compare outcomes between DCD and
      donation after brain death (DBD) liver grafts. Studies reporting on post
      transplantation outcomes after Maastricht category III DCD liver transplantation
      were screened for inclusion. Odds ratios (OR) with 95% confidence intervals were
      produced using random-effects models for the incidence of biliary complications,
      IC, graft and recipient survival. Meta-regression was undertaken to identify
      between-study predictors of effect size for biliary complications and IC.
      PROSPERO Record: CRD42012002113. Twenty-five studies with 62 184 liver transplant
      recipients (DCD = 2478 and DBD = 59 706) were included. In comparison with DBD,
      there was a significant increase in biliary complications [OR = 2.4 (1.9, 3.1); P
      < 0.00001] and IC [OR = 10.5 (5.7, 19.5); P < 0.00001] following DCD liver
      transplantation. In comparison with DBD, at 1 year [OR = 0.7 (0.5, 0.8); P =
      0.0002] and 3 years [OR = 0.6 (0.5, 0.8); P = 0.001], there was a significant
      decrease in graft survival following DCD liver transplantation. At 1 year, there
      was also a nonsignificant decrease [OR = 0.8 (0.6, 1.0); P = 0.08] and by 3 years
      a significant decrease [OR = 0.7 (0.5, 1.0); P = 0.04] found in recipient
      survival following DCD liver transplantation. Eleven factors were entered into
      meta-regression models, but none explained the variability in effect size between
      studies. DCD liver transplantation is associated with an increase in biliary
      complications, IC, graft loss and mortality. Significant unexplained differences
      in effect size exist between centers. 

PMID- 25052037
TI  - Risk of hemorrhage in patients with chronic liver disease and coagulopathy
      receiving pharmacologic venous thromboembolism prophylaxis.
AB  - STUDY OBJECTIVE: To evaluate the impact of pharmacologic venous thromboembolism
      (VTE) prophylaxis on risk of hemorrhage while hospitalized in patients with
      chronic liver disease (CLD) and concurrent coagulopathy. DESIGN: Retrospective,
      multicenter chart review. SETTING: Five hospital, university-affiliated network
      in eastern Pennsylvania. PATIENTS: Patients admitted to the network from January
      1, 2012, until December 31, 2012, with ICD-9 code consistent with CLD and
      elevated international normalized ratio of 1.5 or greater not secondary to
      anticoagulation. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-six patients
      met criteria for analysis, with 80 having received pharmacologic VTE prophylaxis
      and 176 having received no pharmacologic VTE prophylaxis. Differences were
      observed in the primary outcome of overall hemorrhage (composite of major and
      minor hemorrhage) for patients receiving VTE prophylaxis versus no VTE
      prophylaxis (17.5% vs 7.4%, p=0.02). Logistic regression revealed covariates
      independently associated with increased hemorrhage risk were pharmacologic VTE
      prophylaxis use (adjusted odds ratio [AOR] 3.64, p=0.004), increasing
      international normalized ratio (AOR 1.31, p=0.007), and decreasing platelet count
      (AOR 0.99, p=0.03). CONCLUSIONS: Patients with CLD and concurrent coagulopathy
      receiving pharmacologic VTE prophylaxis are at an increased risk of overall
      hemorrhage. Clinical implications remain unclear secondary to the difference in
      rate of overall hemorrhage being driven primarily by a difference in minor
      hemorrhage. In addition, no difference was demonstrated in many assessed
      clinically relevant markers.

PMID- 25052038
TI  - The challenges faced by junior doctors in undertaking research.

PMID- 25052039
TI  - Insect herbivores should follow plants escaping their relatives.
AB  - Neighboring plants within a local community may be separated by many millions of
      years of evolutionary history, potentially reducing enemy pressure by insect
      herbivores. However, it is not known how the evolutionary isolation of a plant
      affects the fitness of an insect herbivore living on such a plant, especially the
      herbivore's enemy pressure. Here, we suggest that evolutionary isolation of host
      plants may operate similarly as spatial isolation and reduce the enemy pressure
      per insect herbivore. We investigated the effect of the phylogenetic isolation of
      host trees on the pressure exerted by specialist and generalist enemies
      (parasitoids and birds) on ectophagous Lepidoptera and galling Hymenoptera. We
      found that the phylogenetic isolation of host trees decreases pressure by
      specialist enemies on these insect herbivores. In Lepidoptera, decreasing enemy
      pressure resulted from the density dependence of enemy attack, a mechanism often
      observed in herbivores. In contrast, in galling Hymenoptera, enemy pressure
      declined with the phylogenetic isolation of host trees per se, as well as with
      the parallel decline in leaf damage by non-galling insects. Our results suggest
      that plants that leave their phylogenetic ancestral neighborhood can trigger,
      partly through simple density-dependency, an enemy release and fitness increase
      of the few insect herbivores that succeed in tracking these plants. 

PMID- 25052040
TI  - On the structure of the thiolated Au6Ag7 cluster.
AB  - The structure of the recently synthesized mercaptosuccinic acid-protected
      Au6Ag7(SR)10 cluster has been elucidated by a DFT approach, following an
      isoelectronic substitution of seven Au atoms by Ag atoms on the [Au13(SR)10](+)
      cluster. After a systematic search for the lowest-energy isomers, it is
      demonstrated that its structure comprises one octahedral-like Ag6 core covered by
      two monoatomic dimer motifs and one Au2Ag1(SR)4 staple-like motif. This result
      confirms that Ag atoms prefer the inner (core) positions while Au atoms are
      located on surface staple-like motifs. 

PMID- 25052042
TI  - Tissues cIMPly do not lie.

PMID- 25052043
TI  - Renoprotective effects of novel interleukin-1 receptor-associated kinase 4
      inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats.
AB  - Renal inflammation is a final common pathway of chronic kidney disease (CKD), and
      its progression can be used to effectively gauge the degree of renal dysfunction.
      Interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK-4) has been reported to
      be a pivotal molecule for IL-1 receptor- and Toll-like receptor-induced signaling
      and activation of proinflammatory mediators. In this study, we hypothesized that
      if inflammation plays a key role in renal failure, then the anti-inflammatory
      effect of IRAK-4 inhibitor should be effective in improving CKD. To determine its
      pharmacological potency, we investigated the renoprotective properties of the
      novel IRAK-4 inhibitor AS2444697 (N-[3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)-1H
      pyrazol-4-yl]-2-(2-methylpyridin-4-yl)-1,3-oxazole-4-carboxamide hydrochloride
      (1:1)) in 5/6 nephrectomized (Nx) rats, a model of CKD. Six weeks' repeated
      administration of AS2444697 (0.3-3 mg/kg, twice daily) dose-dependently and
      significantly reduced urinary protein excretion and prevented the development of
      glomerulosclerosis and interstitial fibrosis without affecting the blood
      pressure. In addition, AS2444697 showed beneficial effects on renal function as
      demonstrated by the decrease in levels of plasma creatinine and blood urea
      nitrogen and attenuation of decline in creatinine clearance. 5/6 Nx rats
      exhibited low-grade inflammation as evidenced by increased renal mRNA expression
      and plasma levels of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and
      MCP-1) and C-reactive protein as a marker of systemic inflammation. AS2444697
      significantly reduced or showed a decreasing trend in expression and levels of
      these inflammatory parameters. These results suggest that AS2444697 suppresses
      the progression of chronic renal failure via anti-inflammatory action and may
      therefore be potentially useful in treating CKD patients. 

PMID- 25052045
TI  - Acetabular wall augmentation in selected patients with recurrent dislocation
      after THA.
AB  - We reviewed 42 patients operated with PMMA augmentation of the acetabular wall
      for recurrent posterior dislocation of cemented total hip arthroplasties with a
      cemented all-poly acetabular component. 38 patients never experienced subsequent
      dislocations after the procedure. 4 patients had recurrent dislocations, and two
      additional patients underwent a revision procedure due to aseptic loosening of
      the acetabular component. 1, 5 and 10 years survival of the prosthesis free of
      dislocation were 95%, 95% and 64% respectively. 90% of the patients were
      satisfied, four patients experienced pain and 3 patients sustained an infection.
      The procedure is simple, effective, takes less time and results in less blood
      loss compared to full revision surgery. It should be considered in cases of
      recurrent posterior dislocation in elderly patients.

PMID- 25052044
TI  - Wild chrysanthemum extract prevents UVB radiation-induced acute cell death and
      photoaging.
AB  - Wild chrysanthemum (Chrysanthemum indicum L.) is traditionally used in folk
      medicine as an anti-inflammatory agent. It is also used in the southwest plateau
      region of China to prevent ultraviolet-induced skin damage. However, the role and
      mechanism by which wild chrysanthemum prevents UV-induced skin damage and
      photoaging have never been investigated in vitro. In the present study, we found
      that aqueous extracts from wild chrysanthemum strongly reduced high-dose UVB
      induced acute cell death of human immortalized keratinocytic HaCat cells. Wild
      chrysanthemum extract was also demonstrated to reduce low-dose UVB-induced
      expression of the photoaging-related matrix metalloproteinases MMP-2 and MMP-9.
      The ROS level elevated by UVB irradiation was strongly attenuated by wild
      chrysanthemum extract. Further study revealed that wild chrysanthemum extract
      reduced UVB-triggered ERK1/2 and p38 MAPK phosphorylation and their protective
      role, which is partially dependent on inhibiting p38 activation. These results
      suggest that wild chrysanthemum extract can protect the skin from UVB-induced
      acute skin damage and photoaging by reducing the intracellular reactive oxygen
      species (ROS) level and inhibiting p38 MAPK phosphorylation. The present study
      confirmed the protective role of wild chrysanthemum against UV-induced skin
      disorders in vitro and indicated the possible mechanism. Further study to
      identify the active components in wild chrysanthemum extract would be useful for
      developing new drugs for preventing and treating skin diseases, including skin
      cancer and photoaging, induced by UV irradiation. 

PMID- 25052046
TI  - Preparation, mechanical, and in vitro properties of glass fiber-reinforced
      polycarbonate composites for orthodontic application.
AB  - Generally, orthodontic treatment uses metallic wires made from stainless steel,
      cobalt-chromium-nickel alloy, beta-titanium alloy, and nickel-titanium (Ni-Ti)
      alloy. However, these wires are not esthetically pleasing and may induce allergic
      or toxic reactions. To correct these issues, in the present study we developed
      glass-fiber-reinforced plastic (GFRP) orthodontic wires made from polycarbonate
      and E-glass fiber by using pultrusion. After fabricating these GFRP round wires
      with a diameter of 0.45 mm (0.018 inch), we examined their mechanical and in
      vitro properties. To investigate how the glass-fiber diameter affected their
      physical properties, we prepared GFRP wires of varying diameters (7 and 13 um).
      Both the GFRP with 13-um fibers (GFRP-13) and GFRP with 7 um fibers (GFRP-7) were
      more transparent than the metallic orthodontic wires. Flexural strengths of GFRP
      13 and GFRP-7 were 690.3 +/- 99.2 and 938.1 +/- 95.0 MPa, respectively; flexural
      moduli of GFRP-13 and GFRP-7 were 25.4 +/- 4.9 and 34.7 +/- 7.7 GPa,
      respectively. These flexural properties of the GFRP wires were nearly equivalent
      to those of available Ni-Ti wires. GFRP-7 had better flexural properties than
      GFRP-13, indicating that the flexural properties of GFRP increase with decreasing
      fiber diameter. Using thermocycling, we found no significant change in the
      flexural properties of the GFRPs after 600 or 1,200 cycles. Using a cytotoxicity
      detection kit, we found that the glass fiber and polycarbonate components
      comprising the GFRP were not cytotoxic within the limitations of this study. We
      expect this metal-free GFRP wire composed of polycarbonate and glass fiber to be
      useful as an esthetically pleasing alternative to current metallic orthodontic
      wire.

PMID- 25052047
TI  - Development and evaluation of an algorithm to identify users of Prolia((r))
      during the early postmarketing period using health insurance claims data.
AB  - PURPOSE: The goal of this study is to develop and validate an algorithm to
      identify Prolia((r)) users within a health insurance claims database. METHODS:
      Patients with a denosumab-specific or nonspecific administration claim during the
      early period of Prolia availability in the USA (June 1, 2010 to March 31, 2012)
      were classified as definite, probable, possible, and nonusers of Prolia using an
      algorithm consisting of nine different components based on claims patterns
      consistent with Prolia use. Medical record review confirmed a sample of definite,
      probable, and possible users and the positive predictive value (PPV) was
      estimated. RESULTS: The PPV of the claims-based algorithm components varied (17.8
      95.8%). Requiring claims for a bone or cartilage disorder or osteoporotic
      fracture after excluding claims for cancer prior to a denosumab-specific
      administration code gave the highest PPV (95.8%), followed by requiring a Prolia
      National Drug Code on the same claim as a denosumab-specific or nonspecific
      administration code (88.2%). Among the 87 confirmed Prolia users, osteoporosis
      diagnoses were seen more frequently in the medical record than in claims (83% vs
      62%). CONCLUSIONS: Prolia users are most accurately identified with
      administration code claims in conjunction with claims for Prolia National Drug
      Code and bone disorder treatment and diagnosis codes. Osteoporosis diagnoses may
      be under-recorded in claims data. The algorithm may require reassessment as
      uptake for more recently approved indications increases.

PMID- 25052048
TI  - An assisted dying law might save me from a lingering and unpleasant death.

PMID- 25052049
TI  - Guaiacol peroxidase zymography for the undergraduate laboratory.
AB  - This laboratory exercise presents a novel way to introduce undergraduate students
      to the specific detection of enzymatic activity by electrophoresis. First,
      students prepare a crude peroxidase extract and then analyze the homogenate via
      electrophoresis. Zymography, that is, a SDS-PAGE method to detect enzyme
      activity, is used to specifically detect peroxidase activity and furthermore, to
      analyze the total protein profile. After the assay, students may estimate the
      apparent molecular mass of the enzyme and discuss its structure. After the 4-h
      experiment, students gain knowledge concerning biological sample preparation, gel
      preparation, electrophoresis, and the importance of specific staining procedures
      for the detection of enzymatic activity.

PMID- 25052050
TI  - Clinical efficacy and safety in relapsed/refractory mantle cell lymphoma: a
      systematic literature review.
AB  - A systematic literature review was performed to collect and review information on
      the clinical efficacy and safety of treatments for relapsed/refractory (R/R)
      mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase,
      and the Cochrane Library were searched for studies published in English from
      January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic
      reference lists of included articles, recent reviews, and ClinicalTrials.gov were
      searched for phase II to IV studies displaying results. Studies were included if
      they reported on patients with R/R MCL who were ineligible to receive high-dose
      chemotherapy with stem cell transplant. Studies of patients with several non
      Hodgkin lymphoma subtypes were only included if they reported MCL outcomes
      separately. We identified 59 studies in R/R MCL. Forty distinct treatment
      regimens were evaluated. Thirty studies included more than 15 patients with R/R
      MCL. Six studies were comparative (including 5 randomized controlled trials
      [RCTs]); 53 were single-arm. There were no common treatments among the RCTs;
      therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported
      baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients
      with R/R MCL, 30 reported overall response rate data, 14 reported progression
      free survival (PFS), and 12 reported overall survival (OS). The small number of
      RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes,
      infrequent reporting of OS and PFS, and limited information on patient
      characteristics made a comparison of results difficult. High-quality comparative
      studies of novel therapies that have the potential to demonstrate OS advantages
      in R/R MCL are needed.

PMID- 25052051
TI  - A phase II, multicenter, open-label study of obatoclax mesylate in patients with
      previously untreated myelodysplastic syndromes with anemia or thrombocytopenia.
AB  - BACKGROUND: Obatoclax mesylate is a small-molecule Bcl-2 homology domain-3
      mimetic that neutralizes antiapoptotic Bcl-2-related proteins. We evaluated
      obatoclax in untreated MDS patients with anemia/thrombocytopenia. PATIENTS AND
      METHODS: Twenty-four patients with a bone marrow blast count of <= 10% and anemia
      (hemoglobin level < 10 g/dL) or thrombocytopenia (platelet count < 50 * 10(9)/L)
      were eligible to receive intravenous obatoclax 60 mg over 24 hours every 2 weeks.
      RESULTS: Response rate was 8% (2 patients; hematologic improvement). Disease
      stabilization/response was maintained >= 12 weeks in 50% (12 patients). Because
      the response rate was below a predetermined threshold, the study was terminated.
      Adverse events (any grade) included euphoric mood (63%; 15 patients), nausea
      (38%; 9 patients), and diarrhea (25%; 6 patients); Grade 3/4 adverse events
      included anemia (21%; 5 patients), thrombocytopenia (13%; 3 patients), and
      pneumonia (13%; 3 patients). CONCLUSIONS: Obatoclax 60 mg every 2 weeks was
      feasible, but had limited first-line activity in MDS.

PMID- 25052052
TI  - Evaluating cell-of-origin subtype methods for predicting diffuse large B-cell
      lymphoma survival: a meta-analysis of gene expression profiling and
      immunohistochemistry algorithms.
AB  - BACKGROUND: Patients with DLBCL exhibit widely divergent outcomes despite
      harboring histologically identical tumors. Currently, GEP and IHC algorithms
      assign patients to 1 of 2 main subtypes: germinal center B cell-like (GCB), or
      activated B cell-like (ABC), the latter of which historically carries a less
      favorable prognosis. However, it remains controversial as to whether these
      prognostic groupings remain valid in the era of rituximab therapy. MATERIALS AND
      METHODS: A systematic literature review identified 24 articles from which meta
      analyses were conducted, comparing survival outcomes for patients assigned to
      either GCB or ABC/non-GCB subtype using GEP and/or Hans, Choi, or Muris IHC
      algorithms. RESULTS: Patients designated as GCB DLBCL using GEP fared
      significantly better in terms of overall survival than those with ABC DLBCL
      (hazard ratio, 1.85; P < .0001). In contrast, the Hans and Choi algorithms failed
      to identify significant differences in overall survival (P = .07 and P = .76,
      respectively) between GCB and non-GCB groups. CONCLUSIONS: Our study illustrates
      a lack of evidence supporting the use of the Hans and Choi algorithms for
      stratifying patients into distinct prognostic groups. Rather, GEP remains the
      preferred method for predicting the course of a patient's disease and informing
      decisions regarding treatment options.

PMID- 25052053
TI  - Amitriptyline-induced agranulocytosis with bone marrow confirmation.

PMID- 25052054
TI  - (11)C-PIB-PET for the early diagnosis of Alzheimer's disease dementia and other
      dementias in people with mild cognitive impairment (MCI).
AB  - BACKGROUND: According to the latest revised National Institute of Neurological
      and Communicative Disorders and Stroke and the Alzheimer's Disease and Related
      Disorders Association (now known as the Alzheimer's Association) (NINCDS-ADRDA)
      diagnostic criteria for Alzheimer's disease dementia, the confidence in
      diagnosing mild cognitive impairment (MCI) due to Alzheimer's disease dementia is
      raised with the application of imaging biomarkers. These tests, added to core
      clinical criteria, might increase the sensitivity or specificity of a testing
      strategy. However, the accuracy of biomarkers in the diagnosis of Alzheimer's
      disease dementia and other dementias has not yet been systematically evaluated. A
      formal systematic evaluation of the sensitivity, specificity, and other
      properties of positron emission tomography (PET) imaging with the (11)C-labelled
      Pittsburgh Compound-B ((11)C-PIB) ligand was performed. OBJECTIVES: To determine
      the diagnostic accuracy of the (11)C- PIB-PET scan for detecting participants
      with MCI at baseline who will clinically convert to Alzheimer's disease dementia
      or other forms of dementia over a period of time. SEARCH METHODS: The most recent
      search for this review was performed on 12 January 2013. We searched MEDLINE
      (OvidSP), EMBASE (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science
      and Conference Proceedings (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS
      (BIREME). We also requested a search of the Cochrane Register of Diagnostic Test
      Accuracy Studies (managed by the Cochrane Renal Group).No language or date
      restrictions were applied to the electronic searches and methodological filters
      were not used so as to maximise sensitivity. SELECTION CRITERIA: We selected
      studies that had prospectively defined cohorts with any accepted definition of
      MCI with baseline (11)C-PIB-PET scan. In addition, we only selected studies that
      applied a reference standard for Alzheimer's dementia diagnosis for example
      NINCDS-ADRDA or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV)
      criteria. DATA COLLECTION AND ANALYSIS: We screened all titles generated by
      electronic database searches. Two review authors independently assessed the
      abstracts of all potentially relevant studies. The identified full papers were
      assessed for eligibility and data were extracted to create two by two tables. Two
      independent assessors performed quality assessment using the QUADAS 2 tool. We
      used the hierarchical summary receiver operating characteristic (ROC) model to
      produce a summary ROC curve. MAIN RESULTS: Conversion from MCI to Alzheimer's
      disease dementia was evaluated in nine studies. The quality of the evidence was
      limited. Of the 274 participants included in the meta-analysis, 112 developed
      Alzheimer's dementia. Based on the nine included studies, the median proportion
      converting was 34%. The studies varied markedly in how the PIB scans were done
      and interpreted.The sensitivities were between 83% and 100% while the
      specificities were between 46% and 88%. Because of the variation in thresholds
      and measures of (11)C-PIB amyloid retention, we did not calculate summary
      sensitivity and specificity. Although subject to considerable uncertainty, to
      illustrate the potential strengths and weaknesses of (11)C-PIB-PET scans we
      estimated from the fitted summary ROC curve that the sensitivity was 96% (95%
      confidence interval (CI) 87 to 99) at the included study median specificity of
      58%. This equated to a positive likelihood ratio of 2.3 and a negative likelihood
      ratio of 0.07. Assuming a typical conversion rate of MCI to Alzheimer's dementia
      of 34%, for every 100 PIB scans one person with a negative scan would progress
      and 28 with a positive scan would not actually progress to Alzheimer's
      dementia.There were limited data for formal investigation of heterogeneity. We
      performed two sensitivity analyses to assess the influence of type of reference
      standard and the use of a pre-specified threshold. There was no effect on our
      findings. AUTHORS' CONCLUSIONS: Although the good sensitivity achieved in some
      included studies is promising for the value of (11)C-PIB-PET, given the
      heterogeneity in the conduct and interpretation of the test and the lack of
      defined thresholds for determination of test positivity, we cannot recommend its
      routine use in clinical practice.(11)C-PIB-PET biomarker is a high cost
      investigation, therefore it is important to clearly demonstrate its accuracy and
      standardise the process of the (11)C-PIB diagnostic modality prior to it being
      widely used.

PMID- 25052056
TI  - Descending branch of the lateral circumflex femoral artery as a recipient vessel
      for vascularized fibular grafts: Clinical case series.
AB  - Vascularized fibular grafts (VFG) are used for the treatment of femoral head
      avascular necrosis, osteomyelitis, nonunions, and excessive bone defects. Mostly
      the ascending branch of the lateral circumflex femoral artery (LCFA) or first or
      second perforating branch of the profound femoral artery is used for the
      customary recipient vessel. In this report, an alternative technique of using
      descending branch of LCFA in VFG surgery and its clinical results are reported.
      Sixteen patients (13 men and 3 women) underwent VFG surgery between the years
      2005 and 2012. Predicted etiologies were: ANFH in 10 hips, traumatic femur neck
      pseudoarthrosis in 4 hips, tumor in 1 hip, and 1 femur shaft defect due to
      osteomyelitis. Patients' average age at the time of surgery was 29 years (range,
      14-43 years). All patients were treated with VFG. All of the grafts survived and
      none of the patients needed any revision surgery. One had superficial wound
      infection, one developed peroneal nerve palsy, and one had trochanteric bursitis.
      The follow-up time was 36 months (range 20-72). It is believed that the
      descending branch of LCFA is a reliable alternative for anastomosis in VFG
      surgery.

PMID- 25052055
TI  - The pathogenesis of optic neuritis caused by Angiostrongylus cantonensis in
      BALB/c mice.
AB  - BACKGROUND: One of the most common causes of meningitis in South East Asia is
      angiostrongyliasis or infection by the parasitic nematode Angiostrongyliasis
      cantonensis. Although this nematode usually resides in the pulmonary arteries of
      rats, its incidental occurence in other hosts such as humans can cause optic
      neuritis and lead to serious vision sequelae. Nevertheless, there are currently
      no systematic studies conducted in this area. METHODS: In order to study the
      pathogenesis of optic neuritis, mice were tried as a new animal model to study
      and challenge with A. cantonensis on 7d, 14d and 21d, respectively.
      Electroretinogram (ERG), visual evoked potential (VEP), ophthalmoscopy and
      histology were examined on day 7d, 14d and 21d and tribendimidine (TBD) was later
      used to treat optic neuritis on day 14d for a week to evaluate its therapeutic
      effects. RESULTS: Infection of A. cantonensis caused obvious inflammatory cell
      infiltration in the retina and optic nerve adventitia in day 14d and 21d followed
      by optic nerve fiber demyelination and retinal ganglion swelling at day 21d in
      the challenged mice. Prolonged VEP latency and decreased ERG amplitude were also
      observed on day 21. After treatment of TBD in the infected mice, retinal and
      optic nerve inflammation were alleviated, but VEP latency and ERG amplitude did
      not improve on day 21d and 28d. CONCLUSIONS: The current study provides evidence
      that A. cantonensis can cause optic neuritis along with optic nerve demyelination
      and retinal ganglion cell damage in a mouse model. TBD alone treatment can
      improve the symptoms of optic neuritis, but does not aid in vision recovery,
      suggesting that both neuroprotective agents and Dexamethasone should be
      administered, along with treatment for the infection, to protect the optic nerve
      and ganglion cells. Furthermore, as the symptoms of optic neuritis caused by A.
      cantonensis in mice are similar to the optic neuritis in multiple sclerosis (MS)
      human patients, we suggest that the BALB/c mouse model provided in this study may
      be useful to explore therapies of optic neuritis in MS patients.

PMID- 25052057
TI  - Cu(1+) in HKUST-1: selective gas adsorption in the presence of water.
AB  - Spectroscopic evidence for an enhanced binding of Nitric Oxide (NO) to metal
      centers with lower oxidation states (open Cu(1+) sites) in Cu3(btc)2 (HKUST-1) is
      presented. The Cu(1+) sites created by thermal treatment or X-ray exposure
      exhibit a preferential adsorption of NO compared to H2O. This phenomenon
      demonstrates the potential use of MOFs with lower oxidation state metal centers
      for selective gas separation. 

PMID- 25052058
TI  - Thyroid anaplastic carcinoma: the impact of multimodality treatment on survival.
      The experience of a referral center for endocrine surgery.
AB  - AIM: Anaplastic thyroid carcinoma (ATC) is characterized by local invasiveness,
      risk of recurrence and very poor prognosis. METHODS: We retrospectively reviewed
      79 consecutive patients treated between 1996 and 2012. We analysed the
      multimodality treatment of ATC considering the impact of surgery and radiotherapy
      on survival. RESULTS: Patients were divided in groups A and B (tumor less and
      larger than 5 cm). Surgery was carried out in 44 patients, radiotherapy in 48
      patients. Tracheostomy and endoprosthesis were used respectively in 48.1% and in
      25.3% of patients. The mean survival was 5.35 (+/- 3.2) months with no
      significant difference in group A vs. group B. Considering patients undergone
      surgery, significant impact on survival was observed comparing A vs. B (P=0.013).
      Combination of surgery and radiotherapy significantly improves outcome comparing
      A vs. B (P=0.017). Improvement in survival compared to no treatment at all was
      observed in both groups respectively for surgery (P=0.001 and P=0.0001) and
      radiotherapy (P=0.047 and P=0.0001). CONCLUSION: Although the severity of
      prognosis of ATC, multimodality treatment still significantly improves local
      control of the disease achieving acceptable survival in selected patients and
      adequate palliation of symptoms for the others. Surgery is still a fundamental
      treatment.

PMID- 25052059
TI  - Effects of pollen season on central and peripheral nitric oxide production in
      subjects with pollen asthma.
AB  - BACKGROUND: Pollen exposure of allergic subjects with asthma causes increased
      nitric oxide (NO) in exhaled air (FENO) suggestive of increased airway
      inflammation. It is, however, unclear to what extent NO production in peripheral
      airways and alveoli are involved. OBJECTIVES: The aim of the present
      investigation was to analyze the relationship between central and peripheral
      components of FENO to clarify the distribution of pollen induced inflammation in
      asthma. SUBJECTS AND METHODS: 13 pollen allergic non-smoking subjects with mild
      intermittent asthma and 12 healthy non-smoking control subjects were examined
      with spirometry and FENO at flows between 50 and 270 mL/s during and out of
      pollen season. RESULTS: Spirometry was normal and unaffected by season in
      subjects with asthma as well as controls. Out of season subjects with asthma had
      significantly higher FENO, elevated airway production (JawNO) and
      preacinar/acinar production (CANO) than controls. Pollen exposure resulted in
      significantly increased FENO and JawNO but not CANO. FENO among controls were not
      affected by season. Individual results showed, however, that CANO increased
      substantially in a few subjects with asthma. The increased CANO in subjects with
      asthma may be explained by increased NO production in preacinar/acinar airways
      and back diffusion towards the alveoli. CONCLUSIONS: The findings may indicate
      that subjects with allergic asthma have airway inflammation without alveolar
      involvement outside the pollen season and pollen exposure causes a further
      increase of airway inflammation and in a few subjects obstruction of intra acinar
      airways causing impeded back diffusion. Increased NO production in central
      airways, unassociated with airway obstruction could be an alternative
      explanation. These effects were not disclosed by spirometry.

PMID- 25052060
TI  - The influence of emotional facial expressions on gaze-following in grouped and
      solitary pedestrians.
AB  - The mechanisms contributing to collective attention in humans remain unclear.
      Research indicates that pedestrians utilise the gaze direction of others nearby
      to acquire environmentally relevant information, but it is not known which, if
      any, additional social cues influence this transmission. Extending upon previous
      field studies, we investigated whether gaze cues paired with emotional facial
      expressions (neutral, happy, suspicious and fearsome) of an oncoming walking
      confederate modulate gaze-following by pedestrians moving in a natural corridor.
      We found that pedestrians walking alone were not sensitive to this manipulation,
      while individuals traveling together in groups did reliably alter their response
      in relation to emotional cues. In particular, members of a collective were more
      likely to follow gaze cues indicative of a potential threat (i.e., suspicious or
      fearful facial expression). This modulation of visual attention dependent on
      whether pedestrians are in social aggregates may be important to drive adaptive
      exploitation of social information, and particularly emotional stimuli within
      natural contexts. 

PMID- 25052062
TI  - Association between TNM staging system and histopathological features in patients
      with papillary thyroid carcinoma.
AB  - We aimed to assess the validity of the American Joint Committee on Cancer (AJCC)
      tumor-node-metastasis (TNM) staging system in patients with papillary thyroid
      carcinoma (PTC) by evaluating the relationships between clinicopathologic factors
      and TNM stage using histopathological specimens and electronic medical records.
      We enrolled 733 consecutive patients who had undergone thyroid surgery for PTC
      between 2010 and 2013. Clinical data were obtained from electronic medical
      records. TNM stages, multifocality, and bilaterality were analyzed after review
      of histopathological specimens by applying the AJCC TNM staging system. Multiple
      statistical analyses were performed to evaluate the correlation between the AJCC
      TNM staging system and the clinicopathologic factors. Of the 733 patients, there
      were T stage including T1a (46.9 %, 344/733), T1b (12.6 %, 92/733), T2 (2.0 %,
      15/733), T3 (38.1 %, 279/733), T4a (0.4 %, 3/733), and T4b (0 %, 0/733), N stage
      including N0 (58.9 %, 432/733), N1a (24.3 %, 178/733), and N1b (16.8 %, 123/733),
      and multiplicity including multifocality (31.1 %, 228/733) and bilaterality (23.7
      %, 174/733). There was a significant association between the PTC primary tumor
      size and T stage, N stage, multifocality, and bilaterality (p < 0.0001).
      Multifocality, bilaterality, and the presence of nodal metastasis were most
      frequently seen in patients with T3 stage (p < 0.0001). In multivariate logistic
      regression analyses, T and N stages were independent predictors of multiple PTCs.
      The PTC primary tumor size had a significant association with the T and N stages
      of the AJCC TNM staging system, and these factors were independent predictors of
      multifocality and bilaterality.

PMID- 25052061
TI  - A comparison of MEmory Specificity Training (MEST) to education and support (ES)
      in the treatment of recurrent depression: study protocol for a cluster randomised
      controlled trial.
AB  - BACKGROUND: Depression is a debilitating mental health problem that tends to run
      a chronic, recurrent course. Even when effectively treated, relapse and
      recurrence rates remain high. Accordingly, interventions need to focus not only
      on symptom reduction, but also on reducing the risk of relapse by targeting
      depression-related disturbances that persist into remission. We are addressing
      this need by investigating the efficacy, acceptability and feasibility of a
      MEmory Specificity Training (MEST) programme, which directly targets an enduring
      cognitive marker of depression - reduced autobiographical memory specificity.
      Promising pilot data suggest that training memory specificity ameliorates this
      disturbance and reduces depressive symptoms. A larger, controlled trial is now
      needed to examine the efficacy of MEST. This trial compares MEST to an education
      and support (ES) group, with an embedded mechanism study. METHODS/DESIGN: In a
      single blind, parallel cluster randomised controlled trial, 60 depressed
      individuals meeting diagnostic criteria for a current major depressive episode
      will be recruited from the community and clinical services. Using a block
      randomisation procedure, groups of 5 to 8 participants will receive five weekly
      sessions of MEST (n = 30) or education and support (n = 30). Participants will be
      assessed immediately post-treatment, and at 3- and 6-months post-treatment (MEST
      group only for 6-month follow-up). Depressive symptoms at 3-month follow-up will
      be the primary outcome. Secondary outcomes will be change in depressive status
      and memory specificity at post-treatment and 3-months. The 6-month follow-up of
      the MEST group will allow us to examine whether treatment gains are maintained.
      An explanatory question will examine variables mediating improvement in
      depression symptoms post-treatment and at 3-month follow-up. DISCUSSION: This
      trial will allow us to investigate the efficacy of MEST, whether treatment gains
      are maintained, and the mechanisms of change. Evidence will be gathered regarding
      whether this treatment is feasible and acceptable as a low-intensity
      intervention. If efficacy can be demonstrated, the results will support MEST as a
      treatment for depression and provide the foundation for a definitive trial. TRIAL
      REGISTRATION: NCT01882452 (ClinicalTrials.gov), registered on 18 June 2013.

PMID- 25052063
TI  - [Bone lesions].

PMID- 25052064
TI  - Flow patterns in inclined-layer turbulent convection.
AB  - We study the flow patterns of turbulent convection in an inclined layer with a
      large aspect ratio Gamma and moderately high Rayleigh numbers ranging from 9 *
      10(4) to 2 * 10(7) based on three-dimensional numerical simulations. The Prandtl
      number is fixed at sigma = 0.7 and the angles of inclination are varied between 5
      degrees  <= theta <= 60 degrees . The initial quiescent fluid layer is observed
      to firstly evolve into a quasi-periodical flow pattern before the turbulent
      convection is fully developed. The transient flow at earlier times, though
      elongated along the slope and anisotropic in the directions parallel to the top
      and bottom plates, becomes isotropic in the final statistically steady state,
      provided that the Rayleigh number is high (R ? 2 * 10(7)) and the angle of
      inclination is small (theta <= 17 degrees ). The effect of inclination on the
      large-scale flow is different from that on individual plumes, which exhibits
      isotropy and is independent of the angles of inclination for Rayleigh numbers
      above 5 * 10(6). The regions near the upper and lower sidewalls of the enclosure,
      considered as extensions of the thermal boundary layer, shrink with increasing
      Rayleigh numbers and the scaling exponent is about 2/7. 

PMID- 25052065
TI  - Study on enthalpy relaxation of glassy polystyrene using a structure-dependent
      Kohlrausch stretch exponent combined with coupling model.
AB  - In this paper the enthalpy relaxation of polystyrene (PS) was restudied using a
      structure-dependent Kohlrausch stretch exponent beta with incorporation of a
      coupling model (CM). The structure dependence of beta is described in 3 semi
      phenomenological equations. The temperature and structure dependence of the
      relaxation time of the Johari-Goldstein (JG) relaxation (tau JG) is presented
      using the traditional Tools-Narayanaswamy-Moynihan (TNM) and Adam-Gibbs-Vogel
      (AGV) equations. The fitting results of heat capacity data are much better than
      the conventional TNM and Adam-Gibbs (AG) models when the structure dependence of
      beta is described using an exponential equation and tau JG is calculated using
      the AGV equation, although there are one fewer fitting parameters in the new
      model. The results indicate that both the structure dependence of beta and the CM
      model may play considerable roles in the investigation on the structure
      relaxation process in polymers around the glass transition. 

PMID- 25052066
TI  - Detecting frogs as prey in the diets of introduced mammals: a comparison between
      morphological and DNA-based diet analyses.
AB  - Amphibians are currently the most threatened group of vertebrates worldwide, and
      introduced fauna play a major role in their decline. The control of introduced
      predators to protect endangered species is often based on predation rates derived
      from diet studies of predators, but prey detection probabilities using different
      techniques are variable. We measured the detectability of frogs as prey, using
      morphological and DNA-based diet analyses, in the stomachs and faeces of four
      mammal species that have been introduced to many areas of the world. Frogs
      (Litoria raniformis) were fed to rats (Rattus norvegicus and R. rattus), mice
      (Mus musculus) and hedgehogs (Erinaceus europaeus). DNA-based analysis
      outperformed morphological analysis, increasing the prey detection rate from 2%
      to 70% in stomachs and from 0% to 53% in faeces. In most cases, utilizing either
      stomachs or faeces did not affect the success of prey DNA detection; however,
      using faeces extended the detectability half-life from 7 to 21 h. This study is
      the first to measure prey DNA detection periods in mammalian stomachs, and the
      first to compare prey DNA detection periods in the stomachs and faeces of
      vertebrates. The results indicate that DNA-based diet analysis provides a more
      reliable approach for detecting amphibians as prey and has the potential to be
      used to estimate the rate of predation by introduced mammals on endangered
      amphibians.

PMID- 25052067
TI  - Acute hyperammonaemia induces a sustained decrease in vigilance, which is
      modulated by caffeine.
AB  - Hyperammonaemia is observed after prolonged, intense exercise, or in patients
      with hepatic failure. In the latter, it is associated with a set of neurological
      and psychiatric abnormalities termed hepatic encephalopathy. THE AIMS OF OUR
      STUDY WERE: 1. to measure vigilance in a condition of induced hyperammonaemia; 2.
      to assess whether caffeine modulates the effects of hyperammonaemia on vigilance,
      if any. Ten healthy volunteers (28.5 +/- 5 years; 5 males) underwent three
      experimental sessions consisting of two-hourly measurements of capillary ammonia,
      subjective sleepiness (Karolinska Sleepiness Scale) and vigilance (Psychomotor
      Vigilance Task, PVT), in relation to the intake of breakfast (+/-coffee), an
      amino acid mixture which induces hyperammonaemia (amino acid challenge; AAC), and
      AAC+coffee (only for participants who had coffee with their standard breakfast).
      The AAC resulted in: 1. the expected increase in capillary ammonia levels, with
      highest values at approximately 4 h after the administration; 2. a significant
      increase in subjective sleepiness ratings; 3. a sustained increase in PVT-based
      reaction times. When caffeine was administered after the AAC, both subjective
      sleepiness and the slowing in RTs were significantly milder than in the AAC-only
      condition. In conclusion, acute hyperammonaemia induces an increase in subjective
      sleepiness and a sustained decrease in vigilance, which are attenuated by the
      administration of a single espresso coffee.

PMID- 25052068
TI  - Next generation sequencing and the future of genetic diagnosis.
AB  - The introduction of next generation sequencing (NGS) has led to an exponential
      increase of elucidated genetic causes in both extremely rare diseases and common
      but heterogeneous disorders. It can be applied to the whole or to selected parts
      of the genome (genome or exome sequencing, gene panels). NGS is not only useful
      in large extended families with linkage information, but may also be applied to
      detect de novo mutations or mosaicism in sporadic patients without a prior
      hypothesis about the mutated gene. Currently, NGS is applied in both research and
      clinical settings, and there is a rapid transition of research findings to
      diagnostic applications. These developments may greatly help to minimize the
      "diagnostic odyssey" for patients as whole-genome analysis can be performed in a
      few days at reasonable costs compared with gene-by-gene analysis based on Sanger
      sequencing following diverse clinical tests. Despite the enthusiasm about NGS,
      one has to keep in mind its limitations, such as a coverage and accuracy of <
      100%, resulting in missing variants and false positive findings. In addition,
      variant interpretation is challenging as there is usually more than one candidate
      variant found. Therefore, there is an urgent need to define standards for NGS
      with respect to run quality and variant interpretation, as well as mechanisms of
      quality control. Further, there are ethical challenges including incidental
      findings and how to guide unaffected probands seeking direct-to-customer testing.
      However, taken together, the application of NGS in research and diagnostics
      provides a tremendous opportunity to better serve our patients.

PMID- 25052069
TI  - Inhibition of epidermal growth factor signaling by the cardiac glycoside ouabain
      in medulloblastoma.
AB  - Epidermal growth factor (EGF) signaling regulates cell growth, proliferation, and
      differentiation. Upon receptor binding, EGF triggers cascades of downstream
      signaling, including the MAPK and phosphoinositide-3-kinase (PI3K)/Akt signaling
      pathways. Aberrant expression/activation of EGFR is found in multiple human
      cancers, including medulloblastoma, the most prevalent pediatric brain cancer,
      and often has been associated with metastasis, poor prognosis, and resistance to
      chemotherapy. Na,K-ATPase is an ion pump well known for its role in intracellular
      ion homeostasis. Recent studies showed that Na,K-ATPase also functions as a
      signaling platform and revealed a role in EGFR, MAPK, and PI3K signaling. While
      both EGFR and Na,K-ATPase seem to modulate similar signaling pathways, cardiac
      glycosides that are steroid-like inhibitors of Na,K-ATPase, exhibit
      antiproliferative and proapoptotic properties in cancer cells. Thus, we sought to
      better understand the relationship between EGF and cardiac glycoside signaling.
      Here, we show that in medulloblastoma cells, both EGF and ouabain activate Erk1/2
      and PI3K/Akt signaling. Nevertheless, in medulloblastoma cells ouabain did not
      transactivate EGFR as has been reported in various other cell lines. Indeed,
      ouabain inhibited EGF-induced Erk1/2 and Akt activation and, moreover, prevented
      EGF-induced formation of actin stress fibers and cell motility, probably by
      activating a stress signaling response. Na,K-ATPase has been proposed to act as a
      signaling scaffold and our studies suggest that in medulloblastoma cells Na,K
      ATPase might act as a check point to integrate EGF-associated signaling pathways.
      Thus, Na,K-ATPase might serve as a valid target to develop novel therapeutic
      approaches in tumors with aberrant activation of the EGFR signaling cascades. 

PMID- 25052070
TI  - Expression of bile duct transcription factor HNF1beta predicts early tumor
      recurrence and is a stage-independent prognostic factor in hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) frequently exhibits biliary
      differentiation, which is typically overlooked. Hepatocyte nuclear factor 1beta
      (HNF1beta), a bile duct-specific transcription factor expressed in bile ducts but
      not in the normal hepatocytes, is also expressed in HCC. MATERIALS AND METHODS:
      The expression of HNF1beta and the biliary differentiation marker cytokeratin 19
      (CK19) were retrospectively evaluated using immunohistochemistry in 159
      surgically resected primary HCCs. RESULTS: A significant correlation was observed
      between HNF1beta protein expression and younger age (p = 0.0293), high serum
      alpha-fetoprotein levels (p = 6 * 10(-4)), and high tumor grade (p = 0.0255).
      However, HNF1beta expression exhibited no correlation with tumor stage. Patients
      with HCCs and HNF1beta expression were more likely to exhibit early tumor
      recurrence (ETR; p = 0.0048) and a lower 5-year survival rate (p = 0.0001). A
      multivariate analysis indicated HNF1beta expression as an independent prognostic
      factor in HCC (p = 0.0048). A combinatorial analysis revealed additive adverse
      effects of HNF1beta when concomitant with CK19 expression and p53 mutation.
      Furthermore, HNF1beta expression can predict poor prognosis in patients with ETR.
      CONCLUSION: Our results indicated that HNF1beta expression is a crucial predictor
      of poor prognosis in HCC and is independent of tumor stage. Moreover, concomitant
      HNF1beta and CK19 expressions exhibited additive adverse effects in HCC,
      confirming that HCC with biliary differentiation has a poor prognosis.

PMID- 25052071
TI  - A comparative analysis of Pancoast tumour resection performed via video-assisted
      thoracic surgery versus standard open approaches.
AB  - OBJECTIVES: The aim of the present paper was to conduct a comparative analysis of
      outcomes after thoracoscopic resection versus standard thoracotomy approach in
      the treatment of Pancoast tumours. METHODS: All consecutive patients with
      Pancoast tumours undergoing surgical treatment from March 2000 to November 2012
      were enrolled. Patients were divided into 2 groups according to whether a
      thoracoscopic or standard thoracotomy approach was adopted. In addition to
      morbidity and mortality, (i) intensity of pain; (ii) respiratory function
      focusing on the postoperative value and its variation with respect to the
      predicted value (Delta); (iii) analgesic consumption at different times during
      the postoperative course; and (iiii) survival rate were recorded in both groups
      and the inter-group differences were statistically compared. RESULTS: Of the 45
      enrolled patients, 34 (75%) were included in the final analysis (18 in the
      thoracoscopic group and 16 in the standard group). Eleven (25%) patients were
      excluded because they (i) were unfit for surgery after induction therapy (n = 4);
      (ii) refused the operation (n = 1) or (iii) had unexpected pleural involvement (n
      = 6). Compared with the standard group, in the thoracoscopic group we observed
      less pain (P = 0.01), better recovery of forced vital capacity (P = 0.01) and
      forced expiratory value in 1 s (P < 0.001), and a reduction in opioid (P = 0.01)
      and analgesic consumption (P = 0.02). The median survival for all patients was 15
      months. Patients with N0/N1 disease had better median survival than N2 patients
      (47 vs 9 months; P = 0.009). One local recurrence in the standard group was
      observed 1 year after operation, whereas 2 local recurrences, 1 in the
      thoracoscopic group and another in the standard group, were registered 2 years
      after the operation (P = 1.0). Finally, 4 (22%) extrathoracic metastases in the
      thoracoscopic group and 5 (31%) in the standard group (P = 0.8) were found over
      the 2 years following the procedure. CONCLUSIONS: In the management of Pancoast
      tumours, a thoracoscopic approach is safe and may be an effective adjunct to
      standard surgical resection in selected cases. Such an approach enabled surgeons
      to explore the pleural cavity and avoid exploratory thoracotomy in cases of
      unexpected pleural involvement.

PMID- 25052072
TI  - Correlation between ventral striatal catecholamine content and nociceptive
      thresholds in neuropathic mice.
AB  - Neuropathic pain is characterized by persistent, intractable pain following
      damage or dysfunction of the nervous system. Analgesics that include central,
      rather than purely peripheral, targets are more effective when treating
      neuropathic pain, highlighting the spinal and/or supraspinal mechanisms that
      contribute to this aberrant pain condition. The striatum represents one of the
      brain regions that have been implicated in pain processing. Release of dopamine
      in the ventral striatum is normally associated with analgesia. Clinical and human
      imaging studies suggest that dopamine is disrupted in neuropathic pain patients,
      although the conclusions drawn from these studies are limited by their
      noninvasive imaging or pharmacologic approaches. In this study, we used a C57Bl/6
      mouse model of neuropathic pain to describe the changes in neurotransmitter
      content in the striatum and their relationship to evoked pain thresholds.
      Striatal dopamine content negatively correlated with mechanical thresholds in
      sham animals. Neuropathic pain animals had reduced dopamine content that was not
      correlated with mechanical thresholds. In contrast, norepinephrine content was
      significantly increased and correlated with mechanical thresholds in neuropathic,
      but not sham, animals. These results describe changes in striatal signaling in
      neuropathic pain animals and contribute to the literature defining the role of
      dopamine and norepinephrine in mediating sensory thresholds in healthy and
      neuropathic pain states. PERSPECTIVE: Results show significant loss of ventral
      striatal dopamine in neuropathic pain conditions, and the relationship of ventral
      striatal catecholamines to pain thresholds is changed in neuropathic pain. These
      results complement human imaging studies and provide evidence that chronic pain
      alters the function of reward systems.

PMID- 25052074
TI  - Implementation of shared decision making in cardiovascular care: past, present,
      and future.

PMID- 25052073
TI  - A nonsense mutation in PLD4 is associated with a zinc deficiency-like syndrome in
      Fleckvieh cattle.
AB  - BACKGROUND: Bovine hereditary zinc deficiency (BHZD) is an autosomal recessive
      disorder of cattle, first described in Holstein-Friesian animals. Affected calves
      suffer from severe skin lesions and show a poor general health status. Recently,
      eight calves with the phenotypic appearance of BHZD have been reported in the
      Fleckvieh cattle population. RESULTS: In spite of the similar disease phenotypes,
      SLC39A4, the gene responsible for BHZD in Holstein-Friesian was excluded as
      underlying gene for the disorder in the affected Fleckvieh calves. In order to
      identify the disease-associated region, genotypes of eight affected calves
      obtained with the Illumina BovineHD BeadChip comprising 777,962 SNPs were
      contrasted with the genotypes of 1,339 unaffected animals. A strong association
      signal was observed on chromosome 21 (P = 5.87 * 10(-89)). Autozygosity mapping
      in the eight affected animals revealed a common segment of extended homozygosity
      encompassing 1,023 kb (BTA 21: 70,550,045 - 71,573,501). This region contains 17
      genes/transcripts, among them two genes encoding gastro-intestinal zinc
      transporters (CRIP1, CRIP2). However, no mutation that was compatible with
      recessive inheritance could be detected in these candidate genes. One of the
      affected calves was re-sequenced together with 42 unaffected Fleckvieh animals.
      Analysis of the sequencing data revealed a nonsense mutation (p.W215X) in a
      phospholipase encoding gene (PLD4) as candidate causal polymorphism. To confirm
      the causality, genotypes of the p.W215X-mutation were obtained from 3,650 animals
      representing three different breeds. None of the unaffected animals was
      homozygous for the defect allele, while all eight affected calves were
      homozygous. The deleterious effect of the mutation is manifested in a
      significantly lower survival rate of descendants from risk matings when compared
      with the survival rate of descendants from non-risk matings. The deleterious
      allele has an estimated frequency of 1.1% in the Fleckvieh population.
      CONCLUSION: Our results provide strong evidence that a newly identified recessive
      disorder in the Fleckvieh population is caused by a nonsense mutation in PLD4,
      most likely resulting in an impaired function of the encoded protein. Although
      the phenotype of affected calves strongly resembles BHZD, a zinc deficiency
      resulting from malabsorption is unlikely to be responsible for the diseased
      Fleckvieh calves.

PMID- 25052075
TI  - Portopulmonary hypertension: improved detection using CT and echocardiography in
      combination.
AB  - OBJECTIVES: To establish the relationship between CT signs of pulmonary
      hypertension and mean pulmonary artery pressure (mPAP) in patients with liver
      disease, and to determine the additive value of CT in the detection of
      portopulmonary hypertension in combination with transthoracic echocardiography.
      METHODS: Forty-nine patients referred for liver transplantation were
      retrospectively reviewed. Measured CT signs included the main pulmonary
      artery/ascending aorta diameter ratio (PA/AAmeas) and the mean left and right
      main PA diameter (RLPAmeas). Enlargement of the pulmonary artery compared to the
      ascending aorta was also assessed visually (PA/AAvis). CT measurements were
      correlated with right-sided heart catheter-derived mPAP. The ability of PA/AAvis
      combined with echocardiogram-derived right ventricular systolic pressure (RVSP)
      to detect portopulmonary hypertension was tested with ROC analysis. RESULTS:
      There were moderate correlations between mPAP and both PA/AAmeas and RLPAmeas (rs
      = 0.41 and rs = 0.42, respectively; p < 0.005). Compared to transthoracic
      echocardiography alone (AUC = 0.59, p = 0.23), a diagnostic algorithm
      incorporating PA/AAvis and transthoracic echocardiography-derived RVSP improved
      the detection of portopulmonary hypertension (AUC = 0.8, p < 0.0001).
      CONCLUSIONS: CT contributes to the non-invasive detection of portopulmonary
      hypertension when used in a diagnostic algorithm with transthoracic
      echocardiography. CT may have a role in the pre-liver transplantation triage of
      patients with portopulmonary hypertension for right-sided heart catheterisation.
      KEY POINTS: * CT signs correlate with right-sided heart catheter data in
      portopulmonary hypertension * CT adds to the transthoracic echocardiography
      detection of portopulmonary hypertension * CT may have a complementary role in
      pre-liver transplantation triage.

PMID- 25052076
TI  - Reduced radiation dose and improved image quality at cardiovascular CT
      angiography by automated attenuation-based tube voltage selection: intra
      individual comparison.
AB  - OBJECTIVES: To evaluate the effect of automated tube voltage selection on
      radiation dose and image quality at cardiovascular CT angiography (CTA). METHODS:
      We retrospectively analysed paired studies in 72 patients (41 male, 60.5 +/- 16.5
      years), who had undergone CTA acquisitions of the heart or aorta both before and
      after the implementation of an automated x-ray tube voltage selection algorithm
      (ATVS). All other parameters were kept identical between the two acquisitions.
      Subjective image quality (IQ) was rated and objective IQ was measured by image
      noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and figure of
      merit (FOM). Image quality parameters and effective dose were compared between
      acquisitions. RESULTS: Overall subjective image quality improved with the
      percentage of cases scored as adequate or higher increasing from 79 % to 92 %
      after implementation of ATVS (P = 0.03). SNR (14.1 +/- 5.9, 15.7 +/- 6.1, P =
      0.009), CNR (11.6 +/- 5.3, 13.2 +/- 5.6, P = 0.011), and FOM (19.9 +/- 23.3, 43.8
      +/- 51.1, P < 0.001) were significantly higher after implementation of ATVS. Mean
      image noise (24.1 +/- 8.4 HU, 22.7 +/- 7.1 HU, P = 0.048) and mean effective dose
      (10.6 +/- 5.9 mSv, 8.8 +/- 5.0 mSv, P = 0.003) were significantly lower after
      implementation of ATVS. CONCLUSIONS: Automated tube voltage selection can
      operator-independently optimize cardiovascular CTA image acquisition parameters
      with improved image quality at reduced dose. KEY POINTS: * Automatic tube voltage
      selection optimizes tube voltage for each individual patient. * In this
      population, overall radiation dose decreased while image quality improved. * This
      tool may become valuable for improving dose/quality ratio.

PMID- 25052077
TI  - Post-mortem cardiac diffusion tensor imaging: detection of myocardial infarction
      and remodeling of myofiber architecture.
AB  - OBJECTIVES: To investigate the accuracy of post-mortem diffusion tensor imaging
      (DTI) for the detection of myocardial infarction (MI) and to demonstrate the
      feasibility of helix angle (HA) calculation to study remodelling of myofibre
      architecture. METHODS: Cardiac DTI was performed in 26 deceased subjects prior to
      autopsy for medicolegal reasons. Fractional anisotropy (FA) and mean diffusivity
      (MD) were determined. Accuracy was calculated on per-segment (AHA
      classification), per-territory, and per-patient basis, with pathology as
      reference standard. HAs were calculated and compared between healthy segments and
      those with MI. RESULTS: Autopsy demonstrated MI in 61/440 segments (13.9 %) in
      12/26 deceased subjects. Healthy myocardial segments had significantly higher FA
      (p < 0.01) and lower MD (p < 0.001) compared to segments with MI. Multivariate
      logistic regression demonstrated that FA (p < 0.10) and MD (p = 0.01) with the
      covariate post-mortem time (p < 0.01) predicted MI with an accuracy of 0.73.
      Analysis of HA distribution demonstrated remodelling of myofibre architecture,
      with significant differences between healthy segments and segments with chronic
      (p < 0.001) but not with acute MI (p > 0.05). CONCLUSIONS: Post-mortem cardiac
      DTI enables differentiation between healthy and infarcted myocardial segments by
      means of FA and MD. HA assessment allows for the demonstration of remodelling of
      myofibre architecture following chronic MI. KEY POINTS: * DTI enables post-mortem
      detection of myocardial infarction with good accuracy. * A decrease in right
      handed helical fibre indicates myofibre remodelling following chronic myocardial
      infarction. * DTI allows for ruling out myocardial infarction by means of FA. *
      Post-mortem DTI may represent a valuable screening tool in forensic
      investigations.

PMID- 25052078
TI  - Toward clinically usable CAD for lung cancer screening with computed tomography.
AB  - OBJECTIVES: The purpose of this study was to define clinically appropriate,
      computer-aided lung nodule detection (CAD) requirements and protocols based on
      recent screening trials. In the following paper, we describe a CAD evaluation
      methodology based on a publically available, annotated computed tomography (CT)
      image data set, and demonstrate the evaluation of a new CAD system with the
      functionality and performance required for adoption in clinical practice.
      METHODS: A new automated lung nodule detection and measurement system was
      developed that incorporates intensity thresholding, a Euclidean Distance
      Transformation, and segmentation based on watersheds. System performance was
      evaluated against the Lung Imaging Database Consortium (LIDC) CT reference data
      set. RESULTS: The test set comprised thin-section CT scans from 108 LIDC
      subjects. The median (+/-IQR) sensitivity per subject was 100 (+/-37.5) for
      nodules >= 4 mm and 100 (+/-8.33) for nodules >= 8 mm. The corresponding false
      positive rates were 0 (+/-2.0) and 0 (+/-1.0), respectively. The concordance
      correlation coefficient between the CAD nodule diameter and the LIDC reference
      was 0.91, and for volume it was 0.90. CONCLUSIONS: The new CAD system shows high
      nodule sensitivity with a low false positive rate. Automated volume measurements
      have strong agreement with the reference standard. Thus, it provides
      comprehensive, clinically-usable lung nodule detection and assessment
      functionality. KEY POINTS: * CAD requirements can be based on lung cancer
      screening trial results. * CAD systems can be evaluated using publically
      available annotated CT image databases. * A new CAD system was developed with a
      low false positive rate. * The CAD system has reliable measurement tools needed
      for clinical use.

PMID- 25052079
TI  - Initial experience of correlating parameters of intravoxel incoherent motion and
      dynamic contrast-enhanced magnetic resonance imaging at 3.0 T in nasopharyngeal
      carcinoma.
AB  - PURPOSE: To determine the correlation between intravoxel incoherent motion (IVIM)
      and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters.
      METHODS: Thirty-eight newly diagnosed NPC patients were prospectively enrolled.
      Diffusion-weighted images (DWI) at 13 b-values were acquired using a 3.0-T MRI
      system. IVIM parameters including the pure molecular diffusion (D), perfusion
      related diffusion (D*), perfusion fraction (f), DCE-MRI parameters including
      maximum slope of increase (MSI), enhancement amplitude (EA) and enhancement ratio
      (ER) were calculated by two investigators independently. Intra- and interobserver
      agreement were evaluated using the intraclass correlation coefficient (ICC) and
      Bland-Altman analysis. Relationships between IVIM and DCE-MRI parameters were
      evaluated by calculation of Spearman's correlation coefficient. RESULTS: Intra-
      and interobserver reproducibility were excellent to relatively good (ICC = 0.887
      0.997; narrow width of 95 % limits of agreement). The highest correlation was
      observed between f and EA (r = 0.633, P < 0.001), with a strong correlation
      between f and MSI (r = 0.598, P = 0.001). No correlation was observed between f
      and ER (r = -0.162; P = 0.421) or D* and DCE parameters (r = 0.125-0.307; P >
      0.119). CONCLUSION: This study suggests IVIM perfusion imaging using 3.0-T MRI is
      feasible in NPC, and f correlates significantly with EA and MSI. KEY POINTS:
      Assessment of tumour perfusion is important in nasopharyngeal carcinoma. DCE-MRI
      provided perfusion information with the use of intravenous contrast media.
      Perfusion information could be provided by non-invasive IVIM MRI. IVIM parameter
      f correlated with DCE-MRI parameters.

PMID- 25052080
TI  - The use of pictograms improves symptom evaluation by patients with functional
      dyspepsia.
AB  - BACKGROUND: No validated patient-reported outcome (PRO) measure exists for
      functional dyspepsia (FD) assessment. Verbal descriptions of different upper
      abdominal symptoms may be poorly distinguishable to patients. AIM: To investigate
      whether understanding of FD symptoms is enhanced by pictograms symbolising the
      nature of the symptoms, besides verbal descriptors. METHODS: Consecutive FD
      patients were randomised to fill out a questionnaire assessing nineupper
      gastrointestinal symptoms (post-prandial fullness, early satiation, epigastric
      pain, epigastric burning, bloating centred in the upper abdomen, nausea,
      vomiting, heartburn, regurgitation) with or without accompanying pictograms.
      Symptoms were rated for frequency and severity (0-5), and patients also
      identified the most bothersome symptom. Subsequently, in-depth history was taken
      by an expert clinician, who filled out the same symptom ratings. Concordance
      between patient and clinician ratings was quantified using chi-square and kappa
      statistics. RESULTS: Content validity of pictograms was first confirmed by 15 FD
      patients. Next, 76 patients (52 women, age 42.2 +/- 1.9) were randomised to
      questionnaires with or without pictograms. The concordance with clinician's
      assessment as gold standard rose from 36 without to 48% for questions with
      pictograms (P < 0.0001). Considering the Rome III subdivision, benefit in
      concordance with pictograms was present for post-prandial distress, epigastric
      pain syndrome and reflux symptoms. Kappa statistics confirmed these gains
      (weighted kappa values for concordance of symptom frequency ratings rose from
      0.214 to 0.446 with pictograms), and also showed better concordance of the most
      bothersome symptom with pictograms. CONCLUSION: Pictograms accompanying verbal
      descriptors significantly improve concordance of functional dyspepsia symptom
      ratings by patients with evaluation by their physicians.

PMID- 25052081
TI  - The inevitability of C4 photosynthesis.
AB  - Elements of C4 photosynthesis-a complex adaptation that increases photosynthetic
      efficiency-may have evolved first to correct an intercellular nitrogen imbalance,
      and only later evolved a central role in carbon fixation. 

PMID- 25052082
TI  - The importance of waiting.
AB  - Neural circuits that prevent a male C. elegans worm from copulating for several
      minutes after ejaculation have been identified. 

PMID- 25052083
TI  - Examining the epidemiology of work-related traumatic brain injury through a
      sex/gender lens: analysis of workers' compensation claims in Victoria, Australia.
AB  - OBJECTIVES: To provide an overview of the epidemiology of work-related traumatic
      brain injury (wrTBI) in the state of Victoria, Australia. Specifically, we
      investigated sex differences in incidence, demographics, injury characteristics,
      in addition to outcomes associated with wrTBI. METHODS: This study involved
      secondary analysis of administrative workers' compensation claims data obtained
      from the Victorian WorkCover Authority for the period 2004-2011. Sex-specific and
      industry-specific rates of wrTBI were calculated using denominators derived from
      the Australian Bureau of Statistics. A descriptive analysis of all variables was
      conducted for the total wrTBI population and stratified by sex. RESULTS: Among
      4186 wrTBI cases identified, 36.4% were females. The annual incidence of wrTBI
      was estimated at 19.8/100 000 workers. The rate for males was 1.43 (95% CI 1.35
      to 1.53) times that for females, but the gap between the two sexes appeared to
      have narrowed over time. Compared to males, females were older at time of injury
      and had lower preinjury income. Males had higher rates than females across most
      industry sectors, with the exception of education/training (RR 0.77, 95% CI 0.64
      to 0.93) and professional/scientific/technical services (RR 0.64, 95% CI 0.44 to
      0.93). For both sexes, the most common injury mechanism was struck by/against,
      followed by falls. WrTBI among males was associated with longer duration of work
      disability and higher claim costs compared to females. CONCLUSIONS: This study
      found significant sex differences in various risk factors and outcomes of wrTBI.
      Sex/gender should be taken into consideration in future research and prevention
      strategies.

PMID- 25052084
TI  - Occupational risk for male infertility.

PMID- 25052085
TI  - Small mine size is associated with lung function abnormality and pneumoconiosis
      among underground coal miners in Kentucky, Virginia and West Virginia.
AB  - OBJECTIVES: To describe the prevalence of lung function abnormality and coal
      workers' pneumoconiosis (CWP) by mine size among underground coal miners in
      Kentucky, Virginia and West Virginia. METHODS: During 2005-2012, 4491 miners
      completed spirometry and chest radiography as part of a health surveillance
      programme. Spirometry was interpreted according to American Thoracic Society and
      European Respiratory Society guidelines, and radiography per International Labour
      Office standards. Prevalence ratios (PR) were calculated for abnormal spirometry
      (obstructive, restrictive or mixed pattern using lower limits of normal derived
      from National Health and Nutrition Examination Survey (NHANES) III) and CWP among
      workers from small mines (<=50 miners) compared with those from large mines.
      RESULTS: Among 3771 eligible miners, those from small mines were more likely to
      have abnormal spirometry (18.5% vs 13.8%, p<0.01), CWP (10.8% vs 5.2%, p<0.01)
      and progressive massive fibrosis (2.4% vs 1.1%, p<0.01). In regression analysis,
      working in a small mine was associated with 37% higher prevalence of abnormal
      spirometry (PR 1.37, 95% CI 1.16 to 1.61) and 2.1 times higher prevalence of CWP
      (95% CI 1.68 to 2.70). CONCLUSIONS: More than one in four of these miners had
      evidence of CWP, abnormal lung function or both. Although 96% of miners in the
      study have worked exclusively under dust regulations implemented following the
      1969 Federal Coal Mine Safety and Health Act, we observed high rates of
      respiratory disease including severe cases. The current approach to dust control
      and provision of safe work conditions for central Appalachian underground coal
      miners is not adequate to protect them from adverse respiratory health effects.

PMID- 25052086
TI  - Von Willebrand factor, a versatile player in gastrointestinal bleeding in left
      ventricular assist device recipients?
AB  - BACKGROUND: Bleeding originating in the gastrointestinal (GI) tract is one of the
      most common adverse events after left ventricular assist device (LVAD)
      implantation. In these patients, GI bleeding appears to be the consequence of
      altered hemostasis on the one hand and alterations of the GI microvasculature on
      the other. CASE REPORT: We report the case of a patient who suffered repeated,
      severe GI bleeding early after implantation of a HeartMate II continuous-flow
      LVAD. RESULTS: After failure of conventional treatment strategies, GI bleeding
      was controlled using repeated transfusions of a purified von Willebrand factor
      (VWF) concentrate, almost devoid of Factor VIII (Wilfactin, LFB). No episodes of
      pump thrombosis were noted. Subsequent to VWF transfusions, we observed a
      progressive normalization of circulating vascular endothelial growth factor
      levels. CONCLUSIONS: Our data raise the possibility that, in addition to its
      hemostatic properties, transfusions of VWF might have acted as an antiangiogenic
      factor.

PMID- 25052087
TI  - All that glitters. ... False elevation of troponin because of heterophile
      antibodies.

PMID- 25052088
TI  - Oral administration of Bacillus subtilis strain BSB3 can prevent heat stress
      related adverse effects in rats.
AB  - AIMS: To determine the efficacy of Bacillus subtilis strain in prevention of heat
      stress-related complications in rats. METHODS AND RESULTS: Male Sprague-Dawley
      rats weighing 250-300 g were treated by oral gavage with B. subtilis BSB3 strain
      or PBS twice a day for 2 days. Half of the rats of each group were exposed to
      heat stress (45 degrees C, relative humidity 55% for 25 min), while the remaining
      rats were placed at identical conditions but at 25 degrees C. Bacterial
      translocation, histological changes in the intestine, cytokines profile, serum
      lipopolysaccharide level (LPS), as well as vesiculation of erythrocytes were
      analysed and compared between groups. Adverse effects of heat stress
      (morphological changes in intestine, bacterial translocation, elevated levels of
      LPS and IL-10, increased vesiculation of erythrocytes) were observed only in rats
      not protected with B. subtilis strain and exposed to heat. All registered
      parameters in rats pretreated with bacilli and exposed to heat were similar to
      control groups. CONCLUSIONS: Bacillus subtilis BS3B strain was effective in the
      prevention of complications related to heat stress in rats. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work will contribute towards better understanding of
      probiotics' mechanisms of action and will bring new approaches to characterize
      and use of beneficial bacteria.

PMID- 25052089
TI  - The molecular basis of emerin-emerin and emerin-BAF interactions.
AB  - Emerin is a conserved membrane component of nuclear lamina structure. Here, we
      report an advance in understanding the molecular basis of emerin function:
      intermolecular emerin-emerin association. There were two modes: one mediated by
      association of residues 170-220 in one emerin molecule to residues 170-220 in
      another, and the second involving residues 170-220 and 1-132. Deletion analysis
      showed residues 187-220 contain a positive element essential for intermolecular
      association in cells. By contrast, deletion of residues 168-186 inactivated a
      proposed negative element, required to limit or control association. Association
      of GFP-emerin with nuclear BAF in cells required the LEM domain (residues 1-47)
      and the positive element. Emerin peptide arrays revealed direct binding of
      residues 170-220 to residues 206-225 (the proposed positive element), residues
      147-174 (particularly P(153)MYGRDSAYQSITHYRP(169)) and the LEM domain. Emerin
      residues 1-132 and 159-220 were each sufficient to bind lamin A or B1 tails in
      vitro, identifying two independent regions of molecular contact with lamins.
      These results, and predicted emerin intrinsic disorder, support the hypothesis
      that there are multiple 'backbone' and LEM-domain configurations in a proposed
      intermolecular emerin network at the nuclear envelope. 

PMID- 25052090
TI  - PARP1-mediated necrosis is dependent on parallel JNK and Ca2+/calpain pathways.
AB  - Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme that can trigger
      caspase-independent necrosis. Two main mechanisms for this have been proposed:
      one involving RIP1 and JNK kinases and mitochondrial permeability transition
      (MPT), the other involving calpain-mediated activation of Bax and mitochondrial
      release of apoptosis-inducing factor (AIF). However, whether these two mechanisms
      represent distinct pathways for PARP1-induced necrosis, or whether they are
      simply different components of the same pathway has yet to be tested. Mouse
      embryonic fibroblasts (MEFs) were treated with either N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) or beta-Lapachone, resulting in PARP1-dependent necrosis.
      This was associated with increases in calpain activity, JNK activation and AIF
      translocation. JNK inhibition significantly reduced MNNG- and beta-Lapachone
      induced JNK activation, AIF translocation, and necrosis, but not calpain
      activation. In contrast, inhibition of calpain either by Ca(2+) chelation or
      knockdown attenuated necrosis, but did not affect JNK activation or AIF
      translocation. To our surprise, genetic and/or pharmacological inhibition of
      RIP1, AIF, Bax and the MPT pore failed to abrogate MNNG- and beta-Lapachone
      induced necrosis. In conclusion, although JNK and calpain both contribute to
      PARP1-induced necrosis, they do so via parallel mechanisms. 

PMID- 25052091
TI  - The splicing factor U1-70K interacts with the SMN complex and is required for
      nuclear gem integrity.
AB  - The nuclear SMN complex localizes to specific structures called nuclear gems. The
      loss of gems is a cellular marker for several neurodegenerative diseases. Here,
      we identify that the U1-snRNP-specific protein U1-70K localizes to nuclear gems,
      and we show that U1-70K is necessary for gem integrity. Furthermore, we show that
      the interaction between U1-70K and the SMN complex is RNA independent, and we map
      the SMN complex binding site to the unstructured N-terminal tail of U1-70K.
      Consistent with these results, the expression of the U1-70K N-terminal tail
      rescues gem formation. These findings show that U1-70K is an SMN-complex
      associating protein, and they suggest a new function for U1-70K in the formation
      of nuclear gems. 

PMID- 25052092
TI  - F-BAR domain protein Rga7 collaborates with Cdc15 and Imp2 to ensure proper
      cytokinesis in fission yeast.
AB  - F-BAR domain proteins act as linkers between the cell cortex and cytoskeleton,
      and are involved in membrane binding and bending. Rga7 is one of the seven F-BAR
      proteins present in the fission yeast Schizosaccharomyces pombe. In addition to
      the F-BAR domain in the N-terminal region, Rga7 possesses a Rho GTPase-activating
      protein (GAP) domain at its C-terminus. We show here that Rga7 is necessary to
      prevent fragmentation of the contracting ring and incorrect septum synthesis.
      Accordingly, cultures of cells lacking Rga7 contain a higher percentage of
      dividing cells and more frequent asymmetric or aberrant septa, which ultimately
      might cause cell death. The Rga7 F-BAR domain is necessary for the protein
      localization to the division site and to the cell tips, and also for the Rga7
      roles in cytokinesis. In contrast, Rga7 GAP catalytic activity seems to be
      dispensable. Moreover, we demonstrate that Rga7 cooperates with the two F-BAR
      proteins Cdc15 and Imp2 to ensure proper cytokinesis. We have also detected
      association of Rga7 with Imp2, and its binding partners Fic1 and Pxl1. Taken
      together, our findings suggest that Rga7 forms part of a protein complex that
      coordinates the late stages of cytokinesis. 

PMID- 25052093
TI  - Ultrastructural analysis of autophagosome organization using mammalian autophagy
      deficient cells.
AB  - Autophagy is mediated by a unique organelle, the autophagosome. Autophagosome
      formation involves a number of autophagy-related (ATG) proteins and complicated
      membrane dynamics. Although the hierarchical relationships of ATG proteins have
      been investigated, how individual ATG proteins or their complexes contribute to
      the organization of the autophagic membrane remains largely unknown. Here,
      systematic ultrastructural analysis of mouse embryonic fibroblasts (MEFs) and
      HeLa cells deficient in various ATG proteins reveals that the emergence of the
      isolation membrane (phagophore) requires FIP200 (also known as RB1CC1), ATG9A and
      phosphatidylinositol (PtdIns) 3-kinase activity. By contrast, small premature
      isolation-membrane-like and autophagosome-like structures were generated in cells
      lacking VMP1 and both ATG2A and ATG2B, respectively. The isolation membranes
      could elongate in cells lacking ATG5, but did not mature into autophagosomes. We
      also found that ferritin clusters accumulated at the autophagosome formation site
      together with p62 (also known as SQSTM1) in autophagy-deficient cells. These
      results reveal the specific functions of these representative ATG proteins in
      autophagic membrane organization and ATG-independent recruitment of ferritin to
      the site of autophagosome formation. 

PMID- 25052094
TI  - A PKA-ezrin-Cx43 signaling complex controls gap junction communication and
      thereby trophoblast cell fusion.
AB  - Cell fusion occurs as part of the differentiation of some cell types, including
      myotubes in muscle and osteoclasts in remodeling bone. In the human placenta,
      mononuclear cytotrophoblasts in a human chorionic gonadotropin (hCG)-driven
      process fuse to form multinucleated syncytia that allow the exchange of nutrients
      and gases between the maternal and fetal circulation. Experiments in which
      protein kinase A (PKA) is displaced from A-kinase anchoring proteins (AKAPs), or
      in which specific AKAPs are depleted by siRNA-mediated knockdown, point to ezrin
      as a scaffold required for hCG-, cAMP- and PKA-mediated regulation of the fusion
      process. By a variety of immunoprecipitation and immunolocalization experiments,
      we show that ezrin directs PKA to a molecular complex of connexin 43 (Cx43, also
      known as GJA1) and zona occludens-1 (ZO-1, also known as TJP1). A combination of
      knockdown experiments and reconstitution with ezrin or Cx43 with or without the
      ability to bind to its interaction partner or to PKA demonstrate that ezrin
      mediated coordination of the localization of PKA and Cx43 is necessary for
      discrete control of Cx43 phosphorylation and hCG-stimulated gap junction
      communication that triggers cell fusion in cytotrophoblasts. 

PMID- 25052095
TI  - The dynamic protein Knl1 - a kinetochore rendezvous.
AB  - Knl1 (also known as CASC5, UniProt Q8NG31) is an evolutionarily conserved
      scaffolding protein that is required for proper kinetochore assembly, spindle
      assembly checkpoint (SAC) function and chromosome congression. A number of recent
      reports have confirmed the prominence of Knl1 in these processes and provided
      molecular details and structural features that dictate Knl1 functions in higher
      organisms. Knl1 recruits SAC components to the kinetochore and is the substrate
      of certain protein kinases and phosphatases, the interplay of which ensures the
      exquisite regulation of the aforementioned processes. In this Commentary, we
      discuss the overall domain organization of Knl1 and the roles of this protein as
      a versatile docking platform. We present emerging roles of the protein
      interaction motifs present in Knl1, including the RVSF, SILK, MELT and KI motifs,
      and their role in the recruitment and regulation of the SAC proteins Bub1, BubR1,
      Bub3 and Aurora B. Finally, we explore how the regions of low structural
      complexity that characterize Knl1 are implicated in the cooperative interactions
      that mediate binding partner recognition and scaffolding activity by Knl1. 

PMID- 25052097
TI  - Microtubule-associated protein (MAP) 4 interacts with microtubules in an
      intrinsically disordered manner.
AB  - We previously used nuclear magnetic resonance (NMR) to analyze the structure of a
      synthetic tricosapeptide corresponding to an active site of microtubule
      associated protein 4 (MAP4). To further the structural analysis, we have
      constructed a minimal active domain fragment of MAP4, encompassing the entire
      active site, and obtained its NMR spectra. The secondary structure prediction
      using partially assigned NMR data suggested that the fragment is largely
      unfolded. Two other independent techniques also demonstrated its unfolded nature,
      indicating that MAP4 belongs to the class of intrinsically disordered proteins
      (IDPs). The NMR spectra of the fragment-microtubule mixture revealed that the
      fragment binds to the microtubule using multiple binding sites, apparently
      contradicting our previous quantitative studies. Given that MAP4 is intrinsically
      disordered, we propose a mechanism in which any one of the binding sites is
      active at a time, which is one of the typical interaction mechanisms proposed for
      IDPs.

PMID- 25052096
TI  - ER-phagy mediates selective degradation of endoplasmic reticulum independently of
      the core autophagy machinery.
AB  - Selective autophagy of damaged or redundant organelles is an important mechanism
      for maintaining cell homeostasis. We found previously that endoplasmic reticulum
      (ER) stress in the yeast Saccharomyces cerevisiae causes massive ER expansion and
      triggers the formation of large ER whorls. Here, we show that stress-induced ER
      whorls are selectively taken up into the vacuole, the yeast lysosome, by a
      process termed ER-phagy. Import into the vacuole does not involve autophagosomes
      but occurs through invagination of the vacuolar membrane, indicating that ER
      phagy is topologically equivalent to microautophagy. Even so, ER-phagy requires
      neither the core autophagy machinery nor several other proteins specifically
      implicated in microautophagy. Thus, autophagy of ER whorls represents a distinct
      type of organelle-selective autophagy. Finally, we provide evidence that ER-phagy
      degrades excess ER membrane, suggesting that it contributes to cell homeostasis
      by controlling organelle size. 

PMID- 25052099
TI  - Patient experiences with intrathecal baclofen as a treatment for spasticity - a
      pilot study.
AB  - PURPOSE: This study describes how patients experience intrathecal baclofen (ITB)
      treatment. METHODS: Data were collected from interviews with 14 patients (19-76
      years old) who were diagnosed with spinal cord injury (SCI), multiple sclerosis
      (MS), or cerebral palsy (CP). Data were analyzed using conventional content
      analysis. RESULT: The analysis resulted in 16 subcategories arranged into five
      main categories: procedures before treatment, the effect of ITB on daily life and
      activities, continuous follow-up, expected and unexpected consequences of ITB,
      and overall level of satisfaction with ITB. Together these categories described
      the patients' experiences with ITB treatment. When the patients were asked
      whether they would undergo ITB again, they all stated that they would.
      CONCLUSION: Patients stated that they were highly satisfied with the ITB
      treatment. However, the patients identified several areas that could be improved.
      Specifically, the patients wanted more information about the different steps in
      the treatment process and what to expect from ITB treatment.

PMID- 25052100
TI  - Participation in life situations by persons with systemic sclerosis.
AB  - PURPOSE: To measure the frequency of participation in life situations. METHODS: A
      sample of 83 persons with systemic sclerosis (SSc) completed questionnaires
      regarding the presence and severity of disease symptoms, disability [the Health
      Assessment Questionnaire (HAQ)], depression [the Center for Epidemiologic Studies
      Depression Scale (CES-D)], and participation [the Adelaide Activities Profile
      (AAP)]. On the AAP, individuals rate the frequency of participation in four
      domains: domestic chores, household maintenance, service to others and social
      activities. RESULTS: Participants were predominantly female, married, educated,
      white, and had diffuse SSc. Mean age was 53.7 years and mean disease duration was
      9.9 years. On the AAP, participation was significantly more frequent for domestic
      chores than for household maintenance, service to others, and social activities.
      More fatigue (p < 0.05), disability (p < 0.001), and fatigue (p < 0.05) resulted
      in lower total AAP scores. More fatigue, pain, severe gastrointestinal symptoms,
      and depression related to lower household maintenance scores, while the presence
      of ulcers and more disability and depression were associated with lower domestic
      chores scores. CONCLUSIONS: Participation in life situations in persons with SSc
      is related to higher disability, depression, and severity of disease symptoms.
      Interventions to address the disability, depression and symptoms may increase
      participation.

PMID- 25052101
TI  - Implementing an inpatient rehabilitation Saturday service is associated with
      improved patient outcomes and facilitates patient flow across the health care
      continuum.
AB  - PURPOSE: To evaluate the effectiveness of the introduction of a Saturday
      inpatient rehabilitation service in improving patient outcomes and facilitating
      hospital access and flow. METHODS: A quasi-experimental study with a historical
      comparison group is presented. Data were evaluated for the 477 patients admitted
      and discharged in the 6 months following the implementation (October 2012-March
      2013) of the service and 499 patients in the historical control group (April 2012
      September 2012). RESULTS: Prior to the introduction of the service median number
      of patients admitted on a Saturday was 0 (range 0-3), post-implementation the
      median number of patients admitted on a Saturday increased to 2 (range 0-5), this
      difference was statistically significant (Z = -3.61, p < 0.001). Median
      regression modelling demonstrated that, after adjusting for admission Functional
      Independence (FIM) score, gender, length of stay (LOS) and age, there was a small
      but significant increase in discharge FIM scores (median increase 2.28, p =
      0.027) for those patients admitted in the post-implementation phase. There was no
      such effect of the service on LOS. CONCLUSIONS: The implementation of the
      Saturday inpatient rehabilitation service was associated with improved patient
      outcomes and supported an increase in patient flow throughout the organization as
      evidenced by an increased number of Saturday patient admissions. IMPLICATIONS FOR
      REHABILITATION: Inpatient rehabilitation services do not operate in isolation;
      they are a critical link in the healthcare continuum. There is a mounting body of
      evidence that the introduction of weekend rehabilitation services has a positive
      impact on patient outcomes. To maximize health outcomes, access to critical
      services and patient flow, organizations and staff need to move away from the
      long-standing 5-day/week inpatient rehabilitation model and start transitioning
      to a model that incorporates weekend therapy services.

PMID- 25052102
TI  - Modulation of amylose content by structure-based modification of OsGBSS1 activity
      in rice (Oryza sativa L.).
AB  - The rice Waxy (Wx) gene encodes granule-bound starch synthase 1 (EC 2.4.1.242),
      OsGBSS1, which is responsible for amylose synthesis in rice seed endosperm. In
      this study, we determined the functional contribution of eight amino acids on the
      activity of OsGBSS1 by introducing site-directed mutated Wx gene constructs into
      the wx mutant glutinous rice. The eight amino acid residues are suspected to play
      roles in OsGBSS1 structure maintenance or function based on homologous enzyme
      sequence alignment and homology modelling. Both OsGBSS1 activity and amylose
      content were analysed in homozygous transgenic lines carrying the mutated OsGBSS1
      (Wx) genes. Our results indicate that mutations at diverse sites in OsGBSS1
      reduces its activity by affecting its starch-binding capacity, its ADP-glucose
      binding capability or its protein stability. Our results shed new light on the
      structural basis of OsGBSS1 activity and the mechanisms of OsGBSS1 activity on
      amylose synthesis in vivo. This study also demonstrates that it is feasible to
      finely modulate amylose content in rice grains by modifying the OsGBSS1 activity.

PMID- 25052103
TI  - [Molecular characterization of beta-lactamase-associated resistance in
      Acinetobacter baumannii strains isolated from clinical samples].
AB  - Acinetobacter baumannii is an important cause of nosocomial infections that
      particularly increase the mortality and the morbidity at the intensive care units
      of the hospitals. The aims of this study were to evaluate the resistance genes,
      antibiotic susceptibility and the clonal relations among Acinetobacter strains
      isolated from clinical samples and to determine the resistance mechanisms related
      to these bacteria in our hospital. A total of 201 A.baumannii strains isolated
      from different clinical samples (35.3% from tracheal aspirate, 27.3% from blood,
      18.4% from abscess material, 19% from other samples) of 160 inpatients evaluated
      at the Ibni Sina Hospital Central Bacteriology Laboratory, Ankara University
      School of Medicine, Turkey from April 2010 to December 2011, were included in the
      study. Identification of the isolates and their susceptibility testing against
      amikacin, ciprofloxacin, tetracycline, sulbactam/ampicillin,
      trimethoprim/sulfametoxazole (SXT), ceftazidime, gentamicin, imipenem,
      levofloxacin, meropenem, piperacillin/tazobactam, cefoperazone/sulbactam,
      cefepime and colistin were performed by the automated systems, namely Vitek 2
      (bioMerieux, France) and BD Phoenix (Becton Dickinson, USA). The molecular
      mechanisms of beta-lactamase resistance and the presence of integrons were
      analyzed by polymerase chain reaction (PCR). Moreover, since blaPER-1 gene is of
      high frequency in Turkey, it was also investigated in the isolates. Pulsed-field
      gel electrophoresis (PFGE) was performed to examine the clonal relations between
      isolates. Our results indicated that multidrug resistance rate of A.baumannii was
      94.5% (190/201), while 94% (189/201) of the isolates were susceptible to colistin
      thus making it the most potent antimicrobial agent, followed by amikacin and SXT
      with a susceptibility rate of 32%. Twelve colistin-resistant isolates were
      further investigated with the E-test method (AB Biodisk, Sweden) and found to be
      colistin-resistant. While the results were negative for the genes responsible
      from metallo-beta-lactamase production, positive results were obtained for blaOXA
      genes at various rates (OXA-51 100%; OXA-23 91.5%; OXA-58 7%; OXA-24 2%). PFGE
      results revealed four different main clones (29 isolates in genotype A, 23 in
      genotype B, 18 in genotype C and 7 in genotype D) in the study population. No
      common epidemic isolate was detected. Class 1 integrons which take part in the
      transfer of resistance genes were detected in 112 (55.7%) isolates. There was no
      statistically significant difference between the genotype distributions of class
      1 integron positive strains (p> 0.05). The relationship between the presence of
      integron in multidrug resistant isolates and resistance to tetracyclin, SXT,
      imipenem, meropenem, cefoperazone/sulbactam and cefepime were found to be
      statistically significant (p< 0.05). Of the isolates 42 (21%) were positive for
      blaPER- 1 gene and all were resistant to ceftazidime. This study indicated that
      blaOXA genes found together with blaOXA-51 genes play an important role in
      carbapenem resistance of A.baumannii strains. Moreover, multidrug resistance is
      still an important problem in infections caused by A.baumannii and integrons play
      a role in the transfer of the resistance genes. In conclusion, multidrug
      resistant A.baumannii strains were common in our hospital and our epidemiologic
      data would be helpful for further investigations and in therapeutical approaches.

PMID- 25052104
TI  - [Identification of staphylococci directly from positive blood culture bottles by
      MALDI-TOF MS system].
AB  - Bloodstream infections are substantial causes of morbidity and mortality
      worldwide. Staphylococcus species are the most commonly isolated microorganisms
      from blood cultures in clinical microbiology laboratories. MALDI-TOF MS (Matrix
      Assisted Laser Desorption/Ionization Time- of- Flight Mass Spectrometry) system
      allows the identification of microorganisms directly from positive blood culture
      bottles. The aim of this study was to evaluate the MALDI-TOF MS system for the
      identification of staphylococci directly from the positive blood culture bottles
      which revealed the presence of gram-positive cocci by staining. A total of 96
      positive blood culture bottles that yielded gram-positive cocci by Gram stain
      were evaluated. These blood cultures were obtained from 69 patients between
      December 2013-February 2014. Conventional methods and BD PhoenixTM automated
      bacterial identification system (Becton Dickinson, USA) were used for routine
      identification. The strains were also identified by real-time Taqman PCR (qPCR)
      which was considered as the reference method. In MALDI-TOF MS method, MALDI
      SepsityperTM Kit was used for the bacterial identification and all measurements
      were carried out by using Microflex LT instrument and FlexControl 3.0 software
      (Bruker Daltonics, USA). Of 96 culture bottles positive for gram-positive cocci,
      90 were correctly identified as staphylococci at genus level with all the three
      study methods (qPCR, BD Phoenix, Bruker MALDI-TOF MS). The other six samples were
      identified as Enterococcus faecium (n= 4) and Streptococcus pyogenes (n= 2) by
      both Phoenix and the MALDI-TOF systems. Of the 90 samples, 87 were identified at
      the species level (15 S.aureus, 33 S.epidermidis, 29 S.hominis, 10
      S.haemolyticus) and three at the genus level by the reference qPCR method. When
      comparing the results obtained by qPCR and Bruker MALDI-TOF MS, incompatibility
      was detected for three isolates. Those isolates were identified as S.hominis by
      qPCR, however two of them were identified as S.haemolyticus and one as
      S.epidermidis by MALDI-TOF MS. Compared with real-time Taqman PCR it was detected
      that Bruker MALDI TOF MS was identified 100% of S.aureus to the genus and species
      level and 100% and 96.6% of coagulase-negative staphylococci (CNS) to the genus
      and species level, respectively. In conclusion, it was thought that Bruker MALDI
      TOF MS system may allow rapid and reliable identification of S.aureus and CNS
      directly from positive blood culture bottles compared with the routine methods
      used in the clinical microbiology laboratory. 

PMID- 25052105
TI  - [Identification of Mycobacterium species from BACTEC MGITTM positive cultures
      with Oligo-FISH and PNA-FISH methods].
AB  - Rapid and accurate diagnosis of mycobacteria is very important in the prevention
      and effective treatment of tuberculosis which is still a serious public health
      problem. Fluorescence in situ hybridization (FISH) method using rRNA targeted
      probes allows for precise and accurate identification of mixed microorganisms
      from cultures and directly from clinical samples within a few hours without the
      need for culture methods. In this study it was aimed to compare the diagnostic
      performance of two different FISH methods (Oligo-FISH and PNA-FISH) with the
      conventional culture methods for the identification of Mycobacterium spp. grown
      in BACTEC MGITTM (Mycobacteria Growth Indicator Tube) system. A total of 60 MGIT
      (BD, USA) positive, 52 MGIT negative samples and 10 different reference strains
      were included in the study. 16S rRNA targeted oligonucleotide probes (Myc657:
      Mycobacterium subdivision, Eub338: Positive control, NonEub: Negative control)
      were used for oligo-FISH, and 16S rRNA targeted peptide nucleotide probes (MTC:
      Mycobacterium tuberculosis complex, NTM: Non-tuberculosis Mycobacterium, BacUni:
      Positive control) for PNA-FISH. Ehrlich-Ziehl-Neelsen staining (ARB) and
      Lowenstein-Jensen (LJ) culture methods were performed as conventional methods as
      well as MGIT 960 culture system. Of MGIT positive 60 samples (44 sputum, 4
      tissue, 4 urine, 3 bronchoalveolar lavage, 3 CSF, 1 abscess, 1 peritoneal fluid),
      29 (48.3%) were found positive for ARB and 44 (73.3%) with LJ culture methods
      giving a total of 59 positive results. Fifty-eight (96.6%) of those isolates were
      identified as MTC, and one (1.7%) as NTM by conventional methods. By using Oligo
      FISH, 95% (57/60) of the isolates were identified as Mycobacterium spp., while
      three samples (5%) yielded negative result. By using PNA-FISH, 54 (91.5%)
      isolates were identified as mycobacteria, of them 53 (90%) were typed as MTC and
      1 (1.7%) as NTM. Five isolates that were found positive with Oligo-FISH, but
      negative with PNA-FISH, yielded positive result with PNA-FISH method performed
      with minor modifications. It was determined that both FISH methods are more rapid
      (approximately 2-2.5 hours) and practical than the conventional culture methods
      and also PNA-FISH was more practical than Oligo-FISH. The sensitivity,
      specificity, positive and negative predictive values of the probes used for Oligo
      FISH, were 96.6%, 100%, 100% and 96.4%, respectively. Those values for the probes
      used for PNA-FISH, were 91.5%, 100%, 100% and 91.4%, respectively (p< 0.0001).
      The compatibility of the methods was calculated with kappa statistical analysis,
      assigning perfect concordances between Oligo- and PNA-FISH methods, as well as
      between conventional and both of the FISH methods (kappa: 0.964, 0.929, 0.964; p=
      0.001). The coverage of oligonucleotide and PNA probes was also checked by using
      16S rRNA gene sequence database retrieved from the SILVA 102. It was determined
      that the rates of coverage were 86.5% for Eub338, 41.7% for Myc657, 84.2% for
      BacUni, 76.3% for MTC (100% for only M.tuberculosis and M.bovis) and 25.8% for
      NTM probes. In conclusion, Oligo- and PNA-FISH methods seem to be successful for
      rapid and accurate identification of Mycobacterium spp. from MGIT positive
      cultures in routine mycobacteriology laboratories without the need for expensive
      methods. 

PMID- 25052106
TI  - [Production of a recombinant CagA protein for the detection of Helicobacter
      pylori CagA antibodies].
AB  - At present, Helicobacter pylori infections affect approximately 50% of the world
      population. It is known that H.pylori is related with several gastric diseases
      including chronic atrophic gastritis, peptic and gastric ulcers as well as
      gastric carcinomas. CagA (Cytotoxin-associated gene A) protein which is one of
      the most important virulence factors of H.pylori, is thought to be responsible
      for the development of gastric cancer. CagA is a 128 kDa hydrophilic protein
      which binds to the epitelial stomach cells and is known to be phosphorylated on
      its EPIYA regions. The EPIYA regions are highly variable and carry a higher risk
      of developing gastric cancer than CagA negative strains. The aim of this study
      was to construct a prokaryotic expression system expressing a recombinant CagA
      protein, which can be used for the detection of anti-CagA antibodies. For the
      isolation of H.pylori genomic DNA, a total of 112 gastric biopsy samples obtained
      from patients who were previously found positive for rapid urease (CLO) test,
      were used. H.pylori DNAs were amplified from 57 of those samples by polymerase
      chain reaction (PCR) and of them 35 were found positive in terms of cagA gene.
      Different EPIYA motifs were detected in 25 out of 35 cagA positive samples, and
      one of those samples that contained the highest number of EPIYA motif, was chosen
      for the cloning procedure. Molecular cloning and expression of the recombinant
      fragment were performed with Champion Pet151/D expression vector (Invitrogen,
      USA), the expression of which was induced by the addition of IPTG (Isopropyl-beta
      D-thiogalactopyranoside) into the E.coli culture medium. Expression was observed
      with anti-histidin HRP (Horse Radish Peroxidase) antibodies by SDS-PAGE and
      Western Blot (WB) analysis. In our study, two clones possessing different
      fragments from the same H.pylori strain with three different EPIYA motifs were
      succesfully expressed. Since CagA antigen plays a signicant role in the
      pathogenesis of H.pylori infections, the detection of anti-CagA antibodies done
      by non-invasive commercial ELISA or WB methods, is important in diagnosis.
      Recombinant CagA protein produced in this study could easily be used in the ELISA
      tests to be developed for screening anti-CagA antibodies in the patients' sera.
      However, since an ELISA method using this antigen has not been developed yet, its
      diagnostic performance could not be evaluated in this study. In conclusion, the
      construction of such a system for recombinant CagA antigen expression may be a
      pilot study for the development of our own ELISA tests in Turkey, and also will
      help the clinicians for the prediction of disease outcome and decision of the
      appropriate antimicrobial treatment by the help of anti-CagA antibody detection. 

PMID- 25052107
TI  - [Tularemia is spreading from north to south side of Turkey: a small outbreak in
      Kahramanmaras, Turkey].
AB  - Tularemia is a zoonotic disease caused by Francisella tularensis. Sporadic
      tularemia cases have been increasingly reported particularly from provinces
      located at northwest and central regions of Turkey especially during last two
      decades, as well as waterborne outbreaks reported from almost all regions.
      Transmission most often occurs through consumption of contaminated water and
      food, thus, oropharyngeal form is the most common clinical presentation in our
      country. The aim of this study was to present a small outbreak experience in
      Afsin, country of Kahramanmaras province located at southern part of Turkey. A
      total of 10 patients (5 male, 5 female; age range 2-68 years; mean age 25 years)
      who were admitted to Afsin State Hospital with the complaints of swollen neck
      between 21 October 2013-22 January 2014, were evaluated considering their
      clinical findings and treatment outcomes. Following the diagnosis of the first
      tularemia case coming from Nadir village, a field investigation was performed.
      All villagers were informed about the disease and water samples from the possible
      sources of outbreak were collected by provincial health authorities. Lymph node
      aspirate and serum samples were sent for culture and serologic investigation and
      the environmental water samples were sent for molecular analysis to the National
      Tularemia Reference Laboratory at Public Health Institution of Turkey. Six out of
      10 patients' sera were found positive in terms of F.tularensis antibodies between
      the titers of 1/320-1/1280 by microagglutination test (MAT) and diagnosis of
      oropharyngeal tularemia was based on the clinical and serological findings. One
      of the patients also presented with oculoglandular form accompanying
      oropharyngeal form. Cultures from aspirate samples that could be obtained from
      only two patients yielded negative results. Three out of six patients' lymph
      nodes were drained surgically and one was drained by ultrasound-guided needle. In
      one case lymph node suppuration occured spontaneously during examination. Three
      of the patients were treated with streptomycin, two with ciprofloxacin and one
      with doxycycline. Although no polymerase chain reaction positivities in terms of
      F.tularensis were detected in the water samples, the outbreak was thought to be
      waterborne since the hygienic conditions of the water sources were inadequate and
      the chlorination procedures were inappropriate. In conclusion, the detection of
      the first case of tularemia and the following small outbreak in Kahramanmaras
      region, emphasized that the disease has had a spreading trend from the endemic
      northern Anatolia to nonendemic southern provinces of Turkey. 

PMID- 25052108
TI  - [HIV-1 subtype distribution determined by phylogenetic analysis of pol gene
      sequences and automated subtyping tools among HIV-1 isolates from the Aegian
      Region of Turkey].
AB  - Human immunodeficiency virus (HIV) exhibiting remarkable genetic variability,
      includes two genotypes namely HIV-1 (group M, N, O and P) and HIV-2 (group A-H).
      HIV-1 group M, which is mainly the cause of the AIDS pandemic, is divided into
      nine pure subtypes, more than 45 circulating recombinant forms (CRF) and numerous
      unique recombinant forms (URF). According to the documents of Turkish Government
      of Health, among a total of 6802 HIV-positive cases, 1096 of them were defined as
      AIDS as of June 2013 in Turkey. Although subtype B is the predominant subtype,
      recent studies indicate higher proportion of CRFs similar to their increasing
      role in the HIV pandemic. The aim of this study was to determine the subtype
      distribution of HIV-1 strains isolated from 70 patients (61 male, 9 female; age
      range: 16-73 yrs, mean age: 39.6 yrs) who presented to our institution between
      April 2008-June 2013. HIV-1 strains were subtyped by phylogenetic analysis of the
      pol gene region and commonly used automated subtyping tools namely, Stanford HIV
      db v6.2.0 and Rega v3.0. Pol sequences retrieved from the Los Alamos database and
      from GeneBank, were trimmed from full-length genomes. Phylogenetic analysis of
      the 1302 base pair of the pol gene region was performed using Mega v5.2 software.
      The sequences were aligned using Muscle and phylogenetic distances between
      sequences were estimated by using Kimura two-parameter model
      (transition/transversion ratio: 2.0). Tree topology was obtained using neighbour
      joining method and bootstrap value was set at 1000. Sixty-one (87.1%) patients
      were antiretroviral treatment (ART)-naive and nine were on different ART
      regimens. The subtypes of the isolates according to phylogenetic analysis were
      found as follows; 31 (44.2%) subtype B, 24 (34.2%) CRF42_BF, 6 (8.5%) B/CRF02_AG
      recombinants, 5 (7.1%) sub-subtype A1, 1 (1.4%) sub-subtype F1, 1 (%1.4) CRF
      25_cpx, 1 (1.4%) CRF02_AG and 1 (1.4%) CRF01_AE. Rega v3.0 subtyping tool
      produced five discrepant results (4 B/CRF02-AG and 1 CRF42_BF) compared to
      phylogenetic analysis. Stanford HIVdb v6.2.0 had eight results (3 CRF42_BF, 2
      subtype B, 2 sub-subtype A1, 1 CRF25_cpx) that were not concordant with
      phylogenetic analysis. Stanford HIVdb v6.2.0 was able to subtype all B/CRF02_AG
      recombinant strains. B/CRF02_AG recombinants which were seen among homosexual men
      in France were for the first time isolated in Turkey from five men (2 homosexual,
      2 bisexual, 1 heterosexual) and one heterosexual woman. CRF42_BF had not been
      found in Turkey previously and it has not been a common type isolated in
      neighboring countries either. Full genome sequencing could be helpful to further
      analysis of those isolates. Our results support the latest studies from Turkey
      reporting increase in the proportion of CRF-related infections. This is not an
      unusual finding when geographical location of Turkey is considered. Nevertheless,
      more comprehensive data regarding molecular epidemiology and subtype distribution
      of HIV-1 isolates in Turkey are needed. 

PMID- 25052109
TI  - [Distribution of hepatitis C virus genotypes among patients with chronic
      hepatitis C infection in Akdeniz University Hospital, Antalya, Turkey: a five
      year evaluation].
AB  - Hepatitis C virus (HCV) is one of the major causes of chronic hepatitis. It is
      important to know the genotypes of HCV in the decision of the HCV related chronic
      hepatitis therapy. The aim of this study was to evaluate the HCV genotypes
      determined at the Microbiology Laboratory of Akdeniz University Hospital, and to
      evaluate the changes in the distribution of the genotypes within the last five
      years. A total of 422 blood samples from HCV-RNA positive chronic hepatitis C
      patients (219 male, 203 female; age range: 8-79 yrs, mean age 46.3 +/- 15.5 yrs)
      which were sent to our laboratory for genotyping between 2009-2013 period, were
      analyzed retrospectively. HCV-RNA extractions were performed in an automated
      system (EZ1 Virus Mini Kit v2.0, Qiagen, Germany), and a commercial reverse
      hybridization line probe-based assay (LIPA; GEN-C RT-PCR, Italy) was carried out
      for genotyping, For viral load determinations, a real-time PCR method (Cobas
      TaqMan HCV, Roche Diagnostics, Germany) was used. Demographic data of the
      patients were obtained from the hospital information systems and electronic
      patients' files. Out of the 422 patients, genotype 1b was detected in 63.3% (n=
      267), genotype 1a in 14.7% (n= 62), genotype 3a in 11.1% (n= 47), genotype 2b in
      0.9% (n= 4), genotype 4e in 0.2% (n= 1). The subtypes couldn't be determined for
      5.4% (n= 23), 2.6% (n= 11) and 1.4% (n= 6) of the patients infected with genotype
      1, 2 and 4, respectively. One (0.2%) patient, was coinfected with genotype 1 and
      4. Of the patients, 40 were foreign-born (16 cases from Russia; 4 of each from
      Ukraine and Georgia; 3 of each from Turkmenistan, Kyrgyzstan, and Germany; one of
      each from Tajikistan, Azerbaijan, Uzbekistan, Chechnya, Moldova, Switzerland and
      Romania) and among these patients genotype 3a (19/40; 47.5%) was the most common
      genotype followed by genotype 1b (17/40; 42.5%). Median values of HCV viral load
      were 668.500 IU/ml (range: 2.000-9.630.000) in the whole group; while it was
      732.000 IU/ml (range: 2.000-9.630.000) in patients infected with genotype 1 and
      444.000 IU/ml (range: 2.650- 8.330.000) in patients infected with the other
      genotypes (p> 0.05). Patients infected with genotype 1 were found to be older
      than those infected with other genotypes (47 +/- 15.7 and 39.5 +/- 12.2,
      respectively; p< 0.001). Among patients infected with different genotypes, there
      was no statistically significant difference in terms of genders (p> 0.05). In
      conclusion, the determination of HCV genotypes is of crucial importance for
      treatment decision-making of chronic HCV infection. Besides, it also allows
      monitoring the changes in the epidemiology of HCV. In this study, although
      genotype 1b was determined as the most common HCV genotype, the detection of
      other genotypes was remarkable. This finding was attributed to the presence of
      many foreign national people in Antalya region which was a high capacity tourism
      area in Turkey. 

PMID- 25052110
TI  - [Comparison of PhoenixTM Yeast ID Panel and API(r) ID 32C commercial systems for
      the identification of Candida species isolated from clinical samples].
AB  - Opportunistic fungal pathogens are one of the important causes of nosocomial
      infections, and several different types of yeasts, especially Candida species are
      increasingly recovered from immunocompromised patients. Since many of the yeasts
      are resistant to the commonly used antifungal agents, the introduction of
      appropriate therapy depends on rapid and accurate identification. The aims of
      this study were to compare the commercial identification systems namely API(r) ID
      32C (bioMerieux, France) and PhoenixTM Yeast ID Panel (Becton Dickinson
      Diagnostics, USA) for the identification of Candida species and to evaluate the
      effect of morphological findings in the identification process. A total of 211
      yeast strains isolated from different clinical samples (111 urine, 34
      blood/vascular catheter, 27 upper/lower respiratory tract, 16 abscess/pus, 13
      throat/vagina swabs and 10 sterile body fluids) of 137 patients hospitalized in
      Uludag University Health and Research Center between October 2013 to January
      2014, were included in the study. Samples were cultured on blood agar,
      chromogenic agar (CHROMagar Candida, BD, USA) and Saboraud's dextrose agar (SDA),
      and isolated yeast colonies were evaluated with germ tube test and morphological
      examination by microscopy on cornmeal/Tween-80 agar. The isolates were identified
      as well by two commercial systems according to the manufacturers'
      recommendations. Discrepant results between the systems were tried to be resolved
      by using morphological characteristics of the yeasts. Of the isolates 159 were
      identified identical by both of the systems, and the concordance between those
      systems were estimated as 75.4%. According to the concordant identification, the
      most frequently isolated species was C.albicans (44.1%) followed by C.tropicalis
      (9.9%), C.glabrata (9.5%), C.parapsilosis (8.5%) and C.kefyr (8.1%). The
      concordance rate was 81.7% in identification of frequently isolated species
      (C.albicans, C.tropicalis, C.parapsilosis, C.glabrata, C.kefyr), however it was
      38.7% for the rarely isolated ones (C.krusei, C.lusitaniae,
      C.inconspicua/C.norvagensis, C.catenulata), representing statistical significance
      (p= 0.034; x2 test). Although not significant (p= 0.31; x2 test), the rate of
      concordance was increased (88.1%), when adding the morphological findings to the
      identification process. Of 211 isolates 37 (17.5%), 50 (23.7%) and 124 (58.8%)
      were identified according to their growth characteristics on chromogenic agar,
      blood agar and SDA, respectively, indicating no statistically significant
      difference between the media (p> 0.05). Although genotypic identification is
      essential, phenotypic methods are more commonly used in routine laboratories for
      the identification of yeast species. However, since genotypic identification
      could not be performed in this study, none of the systems were accepted as the
      standard method and therefore the sensitivity and specificity of the systems were
      not calculated. On the other hand, our data indicated that the two identification
      systems were comparable and careful observation of yeast morphology could add
      confidence to the identification. In conclusion, since the PhoenixTM Yeast ID
      system was found more practical with easier interpretation, and the results were
      obtained earlier than those of the API(r) ID 32C system (16 hours versus 48
      hours), it was thought that PhoenixTM Yeast ID system may be used reliably in the
      routine laboratories. However, as none of the methods evaluated was completely
      reliable as a stand-alone, careful evaluation is necessary for species
      identification. 

PMID- 25052111
TI  - [The effect of Tween-80 on the differentiation of Trichophyton mentagrophytes and
      Trichophyton rubrum strains with FT-IR spectroscopy].
AB  - Trichophyton mentagrophytes and Trichophyton rubrum, are two of the frequently
      identified dermatophyte species in routine microbiology laboratories. Although
      newer technologies may assist in species-level identification, direct application
      of these methods usually require improvement in order to obtain reliable
      identification of these species. Earlier data have shown that dermatophytes may
      be identified with FT-IR spectroscopy although there are some limitations. In
      particular, the organic bond ranges in FT-IR spectra showed more irregularity
      because of the eucaryotic complexity of the molds. In this study, Tween-80 which
      is an inorganic molecule, was added to the dermatophyte growth medium in order to
      investigate its effect on FT-IR spectroscopy analysis of dermatophytes. Nine
      reference dermatophyte strains [5 T.mentagrophytes complex (T.asteroides CBS
      424.63, T.erinacei CBS 344.79, CBS 511.73, CBS 677.86, T.mentagrophytes CBS
      110.65) and 4 T.rubrum complex strains with different morphotypes
      (T.fluviomuniense CBS 592.68, T.kuryangei CBS 422.67, T.raubitschekii CBS 102856,
      T.rubrum CBS 392.58)] were included in the study. All strains were cultured on
      Sabouraud glucose agar either with or without 1% Tween-80 for three weeks. After
      the incubation period, superficial scrapings from each dermatophyte colony were
      analyzed using FT-IR spectroscopy. All measurements were performed in
      transmission mode between 4400 and 400 cm-1. Numerous spectral window data were
      analyzed by principal component analysis and hierarchical clustering was
      performed. The second derivations of spectral ranges revealed clear grouping of
      T.mentagrophytes complex and T.rubrum complex in association over five separate
      spectral ranges. The findings also showed that while all of the T.mentagrophytes
      strains contained lipid compounds in their mold structure after Tween-80
      incubation (p< 0.025), T.rubrum strains did not. Based on these results, it was
      concluded that culture medium containing Tween-80 was sufficient to enable
      differentiation of T.mentagrophytes complex from T.rubrum complex by FT-IR
      spectroscopy. This effect might be attributed to the possible transfer of lipid
      compounds from culture to cell structure during growth. Further studies with the
      use of large number of reference strains and clinical isolates exposed to
      different environmental factors, such as antifungal agents and inorganic ions,
      are needed to support these data indicating favorable effect of Tween-80 on the
      differentiation of T.mentagrophytes and T.rubrum complexes by FT-IR spectroscopy.

PMID- 25052112
TI  - [Evaluation of the diagnostic value of the ELISA tests developed by using EgHF,
      Em2 and EmII/3-10 antigens in the serological diagnosis of alveolar
      echinococcosis].
AB  - Alveolar echinococcosis (AE), caused by larva stage of Echinococcus
      multilocularis, is one of the lethal parasitic diseases of man and a major public
      health problem in many countries in the northern hemisphere. When the living
      conditions and habits in Turkey were considered in terms of relation with the
      life cycle of the parasite, it was suggested that AE has been much more common
      than reported mainly from the Eastern Anatolia region of Turkey. Since in vitro
      serologic diagnosis tests with high specificity for AE have not been used in our
      country, most of the cases with liver lesions were misdiagnosed by radiological
      investigations as malignancies. The aim of this study was to evaluate the
      diagnostic value of the in-house ELISA methods developed by using three different
      antigens (EgHF, Em2, EmII/3-10) in the serological diagnosis of AE. The study
      samples included a total of 100 sera provided by Bern University Parasitology
      Institute where samples were obtained from patients with helminthiasis and all
      were confirmed by clinical, parasitological and/or histopathological means. Ten
      samples from each of the cases infected by E.multilocularis, E.granulosus, Taenia
      solium, Wuchereria bancrofti, Strongyloides stercolaris, Ascaris lumbricoides,
      Toxocara canis, Trichinella spiralis, Fasciola hepatica and Schistosoma
      haematobium were studied. In the study, EgHF (E.granulosus hydatid fluid)
      antigens were prepared in our laboratory from the liver cyst fluids of sheeps
      with cystic echinococcosis, however Em2 (E.multilocularis metacestode-purified
      laminated layer) and EmII/3-10 (E.multilocularis recombinant protoscolex
      tegument) antigens were provided by Bern University Parasitology Institute. Flat
      bottom ELISA plates were covered with EgHF, Em2 and EmII/3-10 antigens in the
      concentrations of 2.5 ug, 1 ug and 0.18 ug per well, respectively, and all sera
      were tested by EgHF-ELISA, Em2-ELISA and EmII/3-10-ELISA methods. For each tests,
      the samples which were reactive above the cut-off value (mean OD of negative
      controls+2 SD) were accepted as positive. The sensitivity of the ELISA tests
      performed with EgHF, Em2 and Em2II/3-10 antigens were estimated as 100%, 90% and
      90%, respectively, whereas the specificity were 63%, 91% and 91%, respectively.
      When Em2-ELISA and EmII/3-10-ELISA tests were evaluated together, the specificity
      increased to 96%. Our data indicated that the highest sensitivity (100% with EgHF
      ELISA) and specificity (96% with Em2-ELISA + EmII/3-10-ELISA) for the
      serodiagnosis of AE can be achieved by the combined use of the ELISA tests with
      three different antigens. It was concluded that the early and accurate diagnosis
      of AE in our country which is endemic for that disease, could be supported by the
      use of highly specific serological tests such as Em2-ELISA ve EmII/3-10-ELISA
      contributing radiological data. 

PMID- 25052113
TI  - [Macrolide-lincosamide-streptogramin B (MLSB) resistance phenotypes in clinical
      Staphylococcus isolates and investigation of telithromycin activity].
AB  - Staphylococci are one of the most common pathogens isolated from nosocomial and
      community acquired infections. Antibiotics such as clindamycin and erythromycin
      have been useful options for treating skin and soft-tissue infections caused by
      staphylococci. However, expression of macrolide-lincosamide-streptogramin B
      resistance (MLSB) can limit the effectiveness of these drugs. The aims of this
      study were to investigate the prevalence and phenotypes of MLSB resistance in
      staphylococcus strains isolated from clinical samples and to determine the
      telithromycin activity against these isolates. A total of 218 strains [92
      Staphylococcus aureus and 126 coagulase-negative staphylococci (CNS)] isolated
      from different clinical samples (wound, abscess, blood, sterile body fluids,
      catheter, upper respiratory tract samples) between February 2011 to December 2012
      were included in the study. The isolates were identified by using conventional
      methods and automated bacterial identification system (BD Phoenix 100TM System,
      Becton Dickinson, USA). Methicillin resistance of the isolates was determined
      with the use of cefoxitin (30 ug) disk and telithromycin (15 ug) activity was
      detected by Kirby-Bauer disk diffusion method. MLSB resistance phenotypes were
      investigated by the D-test method using erythromycin (15 ug) and clindamycin (2
      ug) disks. Of 92 S.aureus isolates, 23 were methicillin-resistant (MRSA) and 69
      were methicillin-susceptible (MSSA), whereas 78 of 126 CNS isolates were
      methicillin-resistant (MRCNS) and 48 were methicillin-susceptible (MSCNS).
      Hundred and seventy-two (79%) isolates were found as erythromycin-resistant, and
      the rates of erythromycin resistance in MRSA, MSSA, MRCNS and MSCNS strains were
      83%, 71%, 95% and 63%, respectively. Inducible type of MLSB resistance (iMLSB
      type) was observed in 26%, 6%, 51% and 33%; chromosomal resistance (cMLSB type)
      in 32%, 27%, 27% and 17% and efflux pump connected resistance (MSB type) in 42%,
      67%, 22% and 50% of the MRSA, MSSA, MRCNS and MSCNS, respectively. Forty-four
      (20%) strains were found susceptible to both clindamycin and erythromycin (S type
      resistance). Resistance due to enzymatic inactivation (L type) was observed only
      in two of the CNS strains (0.9%), one was methicillin-resistant and the other was
      susceptible. Total telithromycin resistance was detected as 26.6% (n= 58), while
      the resistance rates in MRSA, MSSA, MRCNS and MSKNS isolates were 35%, 35%, 28%
      and 8%, respectively. Telithromycin resistance rate was 34% (58/172) in
      erythromycin-resistant isolates. However, all erythromycin-susceptible isolates
      (n= 46) were also susceptible to telithromycin. Telithromycin-resistant isolates
      frequently exhibited cMLSB phenotype (39/44; 67.2%), followed by MSB (16/72;
      27.6%) and iMLSB (3/56; 5.2%). In conclusion, clindamycin is still an effective
      antibiotic for the treatment of staphylococcal infections in our hospital,
      however, 34% resistance rate against telithromycin may limit the use of this
      agent which is an alternative for the treatment of infections caused by
      clindamycin and erythromycin-resistant strains. 

PMID- 25052114
TI  - [Seroprevalence of Bartonella henselae and Bartonella quintana in blood donors in
      Aydin province, Turkey].
AB  - Bartonella species cause several diseases in humans such as cat stratch disease,
      bacillary angiomatosis, peliosis hepatis, endocarditis, Carrion disease and
      trench fever. Cat scratch disease and bacillary angiomatosis cases have already
      been reported in Turkey. Studies from our region, namely Aydin (a province
      located at Western Anatolia, Turkey) indicated that mean Bartonella henselae IgG
      seropositivity rate is 11.5% in risk groups and may reach to 26.5% in pet owners.
      The aim of this study was to determine the seroprevalence of B.henselae and
      B.quintana in healthy blood donors in our university hospital in Aydin, for
      estimating the transmission risk via transfusion. The study was designed as a
      cross-sectional epidemiological study. A total of 333 samples taken from blood
      donors (49 female, 284 male) who were sequentially admitted to the blood center
      of the university hospital, in January 2011 were included in the study. All sera
      were screened in terms of B.henselae and Bartonella quintana IgG antibodies by
      using two different indirect immunofluorescent antibody (IFA) commercial kits
      (Vircell, Spain; Focus, USA). Slides were examined at a final magnification of
      x400 on fluorescent microscope by two different assigned researchers. Fluorescent
      intensity was graded between 1+ to 4+, and the samples with fluorescence value of
      >= 2+ were considered as positive. The seropositivity rate of IgG antibodies to
      B.henselae was found as 3.3% (11/333) in blood donors. This rate was 4.1% in
      female, and 3.2% in male donors, showing no statistically significant difference
      between the genders (p= 0.668). B.henselae antibody titers were detected as 1/64
      in 6 (1.8%), 1/128 in 4 (1.2%) and 1/1024 in 1 (0.3%) patient. All of the
      B.henselae IgG positive samples also yielded relatively low positivity for
      B.quintana IgG, possibly indicating cross reactivity. The fluorescence intensity
      for different kits used was found to be the same in all but one titer. The
      results reported by two researchers were found to differ only in the samples
      graded 1+ or below. However, the evaluation differences between the kits and the
      researchers did not affect the results. It was concluded that B.henselae
      infection might be found in the blood donors in our region, thus, a detailed
      questionnaire prior to blood donation might be helpful to prevent transmission of
      B.henselae by blood transfusion. 

PMID- 25052115
TI  - [Investigation of hepatitis C virus genotype distribution in patients with
      chronic hepatitis C infections in Antalya Training and Research Hospital,
      Turkey].
AB  - Hepatitis C virus (HCV) infection is a major global health problem due to high
      chronicity rates, occurrence of severe hepatic diseases, and absence of an
      accurate therapy and effective vaccine. It is well known that viral genome is
      highly variable and HCV has at least six genotypes, each of them containing a
      series of subtypes. HCV genotypes exhibit geographical and epidemiological
      distribution. Genotype identification is clinically important to decide the
      dosage and duration of treatment since different genotypes exhibit variable
      response to treatment. The aim of this study was to determine the HCV genotypes
      in chronic HCV patients who were followed-up in Antalya Research and Training
      Hospital, Turkey. Anti-HCV and HCV-RNA positive blood samples obtained from 148
      chronic hepatitis C patients (67 female, 81 male; mean age: 50.5 +/- 10.8, age
      range: 17-73 years) who were admitted to Antalya Research and Training Hospital
      Microbiology Laboratory during January 2011-June 2013, were included in the
      study. Epidemiological data of the patients and HCV genotype results were
      evaluated retrospectively. Viral genotypes were determined by real-time (Rt) PCR
      assay (Abbott Molecular Diagnostic, USA). HCV genotype (Gt)-1 was detected in 119
      (80.4%) of the patients, of them 15.9% (19/119) were identified as subtype 1a and
      75.6% (90/119) were subtype 1b. The prevalence rates of Gt-2, -3, and -4 were
      found as 3.4% (n= 5), 11.5% (n= 17), and 2% (n= 3), respectively. Gt-6 was not
      detected in our patients. Mixed infection with HCV types was detected in four
      patients (2.7%) by Rt-PCR; of these three were detected as Gt-1 and one was Gt-2
      by RFLP (Restriction Fragment Length Polymorphism) and sequencing. The high
      prevalence of Gt-3 (11.5%) obtained in this study was attributed to the
      determination of Gt-3 in seven of 13 foreign national subjects. Rt-PCR method
      used in this study is user independent, standardized, automated, rapid and
      reliable method, however in case of detection of mixed types, the samples should
      be confirmed by other methods. In conclusion, we reported that the majority of
      the chronic hepatitis C infected patients had Gt-1b, and Gt-3 exhibited the
      highest rate ever reported by other studies from Turkey. 

PMID- 25052116
TI  - [Investigation of acid proteinase and phospholipase activity as virulence factors
      in clinical Aspergillus spp. isolates].
AB  - Aspergillus spp. are widespread in nature and cause severe infections especially
      in immunocompromised patients. Aspergillus fumigatus complex is the most common
      species that causes infections in humans; however Aspergillus niger complex and
      Aspergillus flavus complex are the emerging agents that are isolated frequently
      from clinical specimens more recently. Besides the host factors such as
      immunosuppression, hematologic malignancy and corticosteroid use, fungal
      virulence factors such as elastase, acid protease and phospholipase enzymes are
      considered among the factors that affect the development of invasive
      aspergillosis. The aim of this study was to detect the acid proteinase and
      phospholipase enzyme activities in 30 A.fumigatus complex, nine A.flavus complex
      and four A.niger complex strains isolated from clinical specimens. Acid
      proteinase and phospholipase activities of the isolates were investigated by
      using bovine serum albumin agar (BSA), and egg yolk agar plates, respectively.
      Acid proteinase and phospholipase activity was detected in 76.7% (23/30) and
      93.3% (28/30) of A.fumigatus complex isolates, respectively. None of the nine
      A.flavus complex isolates exhibited acid proteinase or phospholipase activity.
      Acid proteinase activity was not detected in any of the A.niger complex isolates
      (n= 4), however phospholipase activity was detected in one (25%) isolate. All of
      the acid proteinase positive A.fumigatus complex strains (n= 23) were also
      positive for phospholipase activity. In conclusion, further larger scale
      multicenter studies supported by clinical data, are needed to enlighten the roles
      of acid proteinase and phospholipase in the pathogenesis of infections due to
      Aspergillus spp. 

PMID- 25052117
TI  - [Elizabethkingia meningosepticum bacteremia in a patient with Bardet-Biedl
      syndrome and chronic renal failure].
AB  - Elizabethkingia meningosepticum, a gram-negative opportunistic pathogen may cause
      life-threatening nosocomial infections especially in newborns and
      immunosuppressive patients. This bacterium has a peculiar antibiotic resistance
      profile. It is resistant to most of the antibiotics against gram-negative
      bacteria and susceptible to antibiotics that are used to treat gram-positive
      bacteria, such as vancomycin and trimethoprim-sulphamethoxazole (SXT). For this
      reason appropriate treatment of E.meningosepticum infections are based on the
      proper identification of bacteria. In this report, a case of catheter-related
      E.meningosepticum bacteremia in a patient with chronic renal failure due to
      Bardet-Biedl syndrome, a genetic disorder characterized by multiorgan
      dysfunction, was presented. A 25-year-old male patient with Bardet-Biedl syndrome
      was admitted to the emergency room with the complaints of high fever with shivers
      that started the day before. The patient had a femoral dialysis catheter. Venous
      blood samples drawn at the time of administration were cultured immediately. Two
      days later, blood cultures which yielded positive signals were passaged onto
      blood and MacConkey agar plates and after incubation at 37 degrees C for 16
      hours, wet-raised colonies with clear margin, gray colour and large size similar
      to gram-negative bacterial colonies were detected on blood agar medium. No growth
      was observed on MacConkey agar plate at the end of five days. The isolate was
      found positive for KOH, oxidase, catalase, urease, esculine and MOI (Motility
      Indole Ornithine) tests, whereas it was citrate negative. Gram staining revealed
      faintly stained thin gram-negative bacilli. The isolate was identified as
      E.meningosepticum by Vitek(r) 2 system (bioMerieux, USA), and confirmed by
      sequence analysis of 16S RNA gene region amplified with PCR method. The
      antibiotic susceptibility profile of the strain was detected by the Vitek 2
      system, while vancomycin susceptibility was investigated by Kirby-Bauer disc
      diffusion method. The isolate was found resistant to ampicillin/sulbactam,
      piperacillin/tazobactam, ceftazidime, cefepime, meropenem, imipenem, amikacin,
      gentamicin, netilmicin, levofloxacin, tetracycline, colistin and rifampicin;
      intermediate to tigecyclin and tetracyclin; susceptible to
      cefoperazone/sulbactam, ciprofloxacin, levofloxacin, SXT and vancomycin. One gram
      vancomycin once every four days was administered to the patient, however on the
      ninth day of the treatment he developed fever again. Blood cultures obtained
      again yielded E.meningosepticum. After changing his dialysis catheter and
      extending the vancomycin treatment to 15 days, the patient was discharged with
      cure. In conclusion, clinicians should consider E.meningosepticum as a possible
      causative agent of bacteremia non-responsive to the empirical antibiotic regimens
      and when gram-negative bacteria are isolated from the blood cultures of such
      patients with underlying diseases. Accurate and prompt identification of
      E.meningosepticum will allow immediate administration of the specific antibiotic
      treatment, thereby decreasing the mortality and morbidity rates. 

PMID- 25052118
TI  - [Cladophilaphora bantiana brain abscess treated with voriconazole in an
      immunocompetent patient].
AB  - Phaeohyphomycosis is a term used to define infections caused by darkly pigmented
      fungi with septate hyphae which contain melanin in their cell walls. Although
      fungi rarely cause central nervous system (CNS) infections, the incidence of CNS
      infections caused by melanin-containing fungi has been increasing in the recent
      years. Cladophialophora bantiana is the most frequently isolated species from
      cerebral phaeohyphomycosis. It mostly affects adult men in the second and third
      decade of life and about half of the cases occurs in immunocompetent patients. In
      this report, the isolation of C.bantiana from brain tissue of an immunocompetent
      patient who was operated with the initial diagnosis of a brain abscess, was
      presented. A 27 year-old male patient presenting without any chronic disease was
      admitted to the emergency department of our hospital with the complaints of
      persistent headache and diplopia. Magnetic resonance imaging (MRI) showed a space
      occupying lesion in the right parietal lobe and left frontal lobe. Brain abscess
      was diagnosed in the patient who was referred to the neurosurgery department.
      Treatment was initiated with ceftriaxone and metronidazole. The abscess material
      sent for direct microscopic examination in the mycology laboratory was stained
      with Gram and Giemsa and cultured in the Sabouraud dextrose agar medium (SDA)
      with and without antibiotics (cycloheximide and chloramphenicol). Then, it was
      incubated at 37 degrees C and 25 degrees C. Direct examination and staining
      revealed a septate hyphae. The patient who received liposomal amphotericin B was
      referred to the infectious diseases department. Surface colors of all media
      including SDA with cycloheximide were olive-gray to black and contained velvety
      colonies. Lemon-like very long and integrated chains of conidium with poor
      branching in cornmeal Tween 80 agar, as well as growth at 42 degrees C in
      passages, positive urease test result and cycloheximide resistance suggested
      C.bantiana. The isolate was confirmed as C. bantiana based on its DNA sequence
      analysis. Minimum inhibitor concentration (MIC) values for amphotericin B,
      voriconazole, caspofungin, and posaconazole were 2 ug/ml, 0.03 ug/ml, 0.03 ug/ml
      and 0.03 ug/ml, respectively. Liposomal amphotericin B was replaced with
      voriconazole due to the antifungal susceptibility profile. The patient who was
      symptom-free was discharged at 24 days after hospitalization with oral
      voriconazole treatment. In conclusion, cerebral phaeohyphomycosis should be
      considered in immunocompetent individuals. Given the fact that early diagnosis
      saves lives, such specimens should promptly be sent for mycological analysis. 

PMID- 25052119
TI  - [A rarely seen cause of brain abscess: neurotoxocariasis].
AB  - Toxocariasis in man is associated with three syndromes which are visceral larva
      migrans, ocular larva migrans and covert toxocariasis. Although neurotoxocariasis
      is defined as the fourth syndrome of toxocariasis, it is usually considered as a
      neurological disease which is usually concomitant with visceral larva migrans. In
      this report, a case of brain abscess caused by toxocariasis was presented. A 56
      years-old female patient was admitted to our hospital with headache, pain
      referring to right side of her face and teeth, numbness of forth and fifth finger
      of her right hand. Cranial diffusion weighted, dynamic magnetic resonance imaging
      (MRI) revealed a few non-specific intensities at supratentorial white matter, an
      approximately 13 x 12 mm lesion without contrast enhancement and a significant
      edema around the white matter in the left frontal cortex. Histologic examination
      after stereotactic biopsy of the lesion revealed diffuse histiocyte infiltration.
      A specific agent could not be detected in the histochemical examination. Western
      blot test for toxocariasis in serum and cerebrospinal fluid samples were found
      positive. She was transferred to the infectious diseases clinic, and albendazole
      therapy (400 mg, q12h) was started. Albendazole treatment was completed for a
      total of one month following the regression of the cranial MRI findings on the
      14th day of therapy. The patient is recalled for cranial MRI control three months
      later. However, it was noted that she continued albendazole for three months.
      Compared to the previous MRI, there were two stabilized T2A hyperintense lesions
      in left cranial hemisphere and minimally regressed lesions at the level of left
      frontal centrum semiovale. The patient was successfully treated with albendazole.
      There was no relapse after six month follow-up. This case was presented to
      withdraw attention to neurotoxocariasis which may be encountered although rarely
      in the etiology of encephalitis/ brain abscess. 

PMID- 25052120
TI  - [A case of gingival myiasis caused by Wohlfahrtia magnifica].
AB  - Myiasis is an infestation of living or dead tissue of humans and animals by
      diptera larvae. Gingival myiasis is a rare pathology and is mainly associated
      with poor oral hygiene, alcoholism, senility, suppurative lesions, mouth
      breathing, mental retardation and hemiplegia. Myiasis is most common during
      summer since the fly population increases during this season. Mostly it occurs in
      farmers and people who live in tropical climates. Gingival myiasis in humans in
      Turkey is limited to only a few cases. According to our literature research, this
      is the first case of gingival myiasis produced by larvae of Wohlfahrtia magnifica
      in a Turkish adult. According to our best knowledge, it is also the first
      gingival myiasis case that one of the causative larva had grown to the adult
      stage in Turkey. A 43 years old male patient who perceived the presence of live
      maggots in his mouth was referred to our clinic. Clinical findings of gingival
      myiasis were observed. The patient had no history of systemic disease but oral
      hygiene was poor. Clinical and radiographic examination indicated that he had
      chronic periodontitis. Before the dental treatment seven larvae and during the
      scalling five larvae were elevated from the gingival sulcus. The body of the
      larvae composed of 12 segments and they were 8-10 mm in length. One of the larvae
      which was sent to the microbiology laboratory were placed into sheep liver to
      resume life and the other larvae were placed into 70% alcohol solution. After 9
      10 days, the larva which was placed in the liver became pupa. Approximately 15
      days later, the pupa became an adult fly. The larvae were identified as the
      second stage larvae of Wohlfahrtia magnifica. Treatment consisted of removal of
      the maggots from the gingival sulcus, followed by scaling and oral hygiene
      instruction. Non-surgical periodontal treatment was applied and the patient was
      followed-up for 3 months. After non-surgical periodontal treatment, patient
      didn't accept the flap operation. The most important point for the prevention of
      gingival myiasis is to establish a good oral hygiene, together with the
      elimination of environmental factors which support the proliferation of the
      flies. 

PMID- 25052121
TI  - [Contribution to determination of hepatitis C virus genotypes in Black Sea
      region: data from single high volume center in Zonguldak, Turkey].
AB  - We've read with great interest the article entitled "Determination of hepatitis C
      virus genotypes among hepatitis C patients in Eastern Black Sea Region, Turkey"
      by Buruk et al. published in Mikrobiyol Bul 2013; 47(4): 650-7. In that study,
      the authors described the determination and distribution of hepatitis C virus
      (HCV) genotypes in Eastern Black Sea Region comprehensively. According to the
      current information, the determination of HCV genotypes is the most important
      factor for the management of therapy and virus-related complications, such as
      chirrhosis and hepatocellular carcinoma. The distribution of HCV genotypes varies
      geographically throughout the world. Therefore every country and even each region
      within the country should know the distribution of HCV genotypes to determine the
      appropriate treatment strategy. Herein we would like to contribute the data about
      distribution of HCV genotypes in whole Black Sea Region by presenting our current
      results obtained from Zonguldak province, where maximum number of chronic hepatit
      C patients have already been identified in Eastern Black Sea Region. A total of
      53 chronic hepatitis C patients (26 female, 27 male; mean age: 57.1 +/- 14.3, age
      range: 21-82 years) who were admitted to Zonguldak Ataturk State Hospital between
      January 2012-December 2013 were evaluated. Genotype analysis was performed by
      RealTime HCV Genotype II (Abbott Molecular, ABD) system. Genotype-1 was found to
      be the most frequently detected type with a rate of 96.2% (51/53). The
      prevalences of genotype-2 (1/53) and genotype-4 (1/53) were same, with a rate of
      1.9%, in our study. Subtyping of genotype-1 strains yielded 52.9% (27/51)
      genotype-1b, 3.9% genotype-1a (2/51) and 47% untypeable genotype-1 (24/51). The
      present study was the second study from the Western Black Sea Region in our
      country, regarding HCV genotypes. In conclusion, considering entire Black Sea
      Region, genotype-1 is the most common genotype (96.2%), and 1b (52.9%) is the
      most common subtype, in parallel to the data reported from the other regions of
      Turkey. 

PMID- 25052122
TI  - Ospemifene for the treatment of vulvovaginal atrophy and dyspareunia in
      postmenopausal women.
AB  - Vulvovaginal atrophy (VVA) and dyspareunia are common problems experienced by
      postmenopausal women, although few seek treatment. Symptom-based therapies
      include nonhormonal vaginal lubricants, vaginal moisturizers, low-dose vaginal
      estrogen, and systemic estrogen. The 2013 United States Food and Drug
      Administration approval of ospemifene, an estrogen agonist/antagonist for the
      treatment of moderate-to-severe dyspareunia associated with VVA, increased
      options available to women. Several studies have evaluated the effects of
      ospemifene on VVA and dyspareunia and indicate an improvement in subjective
      findings. Objective findings such as a decrease in pH and recovery of a
      premenopausal vaginal maturation index have been reported. Beneficial effects
      have also been demonstrated in bone. Evaluations of breast health support the
      safety of ospemifene, although data are limited to 1 year. Short-term risks
      appear to be limited and include the development of hot flushes. Until additional
      comparative studies of ospemifene and estrogens have been performed, ospemifene
      should be recommended for women with symptoms of VVA and dyspareunia who are
      unable to tolerate or unwilling to take local or systemic estrogens. In this
      review, current evidence for the safety and efficacy of ospemifene in the
      treatment of moderate-to-severe VVA and dyspareunia are evaluated. 

PMID- 25052123
TI  - Surgical treatments for rectal prolapse: how does a perineal approach compare in
      the laparoscopic era?
AB  - BACKGROUND: Patients with rectal prolapse often have significant comorbidities
      that lead surgeons to select a perineal resection for treatment despite a
      reported higher recurrence rate over abdominal approaches. There is a lack of
      data to support this practice in the laparoscopic era. The objective of this
      study was to evaluate if risk-adjusted morbidity of perineal surgery for rectal
      prolapse is actually lower than laparoscopic surgery. DESIGN: A retrospective
      review of the American College of Surgeons National Surgical Quality Improvement
      Program (NSQIP) database as performed for patients undergoing surgical treatment
      of rectal prolapse between 2005 and 2011. Outcomes were analyzed according to
      procedure-type: laparoscopic rectopexy (LR), laparoscopic resection/rectopexy
      (LRR), open rectopexy (OR), open resection/rectopexy (ORR), and perineal
      resection (PR). A multivariate logistic regression was used to compare risk
      adjusted morbidity and mortality between each procedure. Main outcome measures
      were 30-day morbidity and mortality. RESULTS: Among 3,254 cases sampled, a
      laparoscopic approach was used in 22 %, an open abdominal approach in 30 %, and
      PR in 48 %. Patients undergoing PR were older (76) and had a higher ASA (3)
      compared to laparoscopic (58, 2) and open abdominal procedures (58, 2). Risk
      adjusted mortality could not be assessed due to a low overall incidence of
      mortality (0.01 %). Overall morbidity was 9.3 %. ORR was associated with a higher
      risk-adjusted morbidity compared to PR (OR: 1.89 CI (1.19-2.99), p = 0.03). There
      were no significant differences in risk-adjusted morbidity found between LR and
      LRR compared to PR (OR 0.44 CI (0.19-1.03), p = 0.18; OR 1.55 CI (0.86-2.77), p =
      0.18). Laparoscopic cases averaged 27 min longer than open cases (p < 0.001).
      CONCLUSION: Laparoscopic rectal prolapse surgery has comparable morbidity and
      mortality to perineal surgery. A randomized trial is indicated to validate these
      findings and to assess recurrence rates and functional outcomes.

PMID- 25052124
TI  - Impact of previous midline laparotomy on the outcomes of laparoscopic intestinal
      resections: a case-matched study.
AB  - The effectiveness of laparoscopic intestinal resection in patients with previous
      midline laparotomy (PML) is controversial. The aim of this study was to assess
      the feasibility of laparoscopic surgery and identify possible factors associated
      with postoperative outcomes in patients with PML. Patients with PML (at least an
      infraumbilical incision or longer) undergoing elective laparoscopic intestinal
      resection between 1997 and 2011 were case matched with patients without PML
      undergoing laparoscopic surgery based on age, gender, body mass index, ASA score,
      surgical procedure, and diagnosis. Fifty patients with PML undergoing
      laparoscopic intestinal resection were well matched to 50 counterparts.
      Conversion to open surgery (n = 8 vs. n = 4, p = 0.22), operating time (211 vs.
      192 min, p = 0.22), and estimated blood loss (158 vs. 184 ml, p = 0.95) were
      similar between the groups. Intraabdominal adhesions (either disease related or
      from previous operations) were significantly more common in patients with PML (n
      = 24 vs. n = 11, p = 0.01). Intraoperative complications included inadvertent
      enterotomy and hemorrhage and were comparable between the groups (n = 1 vs. n =
      0, p = 1 and n = 1 vs. n = 2, p = 1 for PML vs. no PML, respectively). One
      patient without PML died postoperatively from aspiration pneumonia. Overall
      morbidity (n = 26 vs. n = 10, p = 0.001) and particularly postoperative ileus (n
      = 10 vs. n = 3, p = 0.04) were significantly increased in the PML group when
      compared to laparoscopy without PML, unlike the respective differences in
      postoperative return of bowel function (4 vs. 3 days, p = 0.15), reoperations (n
      = 5 vs. n = 3, p = 0.72), length of hospital stay (9 vs. 6 days, p = 0.09), and
      readmissions (n = 5 vs. n = 4, p = 0.73). Intestinal resections in patients with
      PML can be frequently completed laparoscopically but are associated with worse
      postoperative outcomes when compared to laparoscopy on a virgin abdomen.

PMID- 25052125
TI  - Complete closure of artificial gastric ulcer after endoscopic submucosal
      dissection by combined use of a single over-the-scope clip and through-the-scope
      clips (with videos).
AB  - BACKGROUND: A 5-7 day hospital stay is usually needed after endoscopic submucosal
      dissection (ESD) of gastric tumor because of the possibility of delayed
      perforation or bleeding. The aim of this study was to evaluate the efficacy of
      combined use of a single over-the-scope clip (OTSC) and through-the-scope clips
      (TTSCs) to achieve complete closure of artificial gastric ulcer after ESD.
      METHODS: We prospectively studied 12 patients with early gastric cancer or
      gastric adenoma. We performed complete closure of post-ESD artificial gastric
      ulcer using a combination of a single OTSC and TTSCs. RESULTS: Mean size of post
      ESD artificial ulcer was 54.6 mm. The mean operating time for the closure
      procedure was 15.2 min., and the success rate was 91.7 % (11/12). Patients who
      underwent complete closure of post-ESD artificial gastric ulcer could be
      discharged the day after ESD and the closing procedure. CONCLUSIONS: Complete
      closure of post-ESD artificial gastric ulcer using a combination of a single OTSC
      and TTSCs is useful for shortening the period of hospitalization and reducing
      treatment cost.

PMID- 25052126
TI  - Postoperative complications following single-incision laparoscopic
      cholecystectomy: a retrospective analysis in 360 consecutive patients.
AB  - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is being
      increasingly performed based on recent evidence showing its cosmetic advantages.
      However, there is limited information on outcome data for SILC with respect to
      postoperative complications. METHODS: We retrospectively reviewed a consecutive
      series of 360 patients undergoing SILC to evaluate the rate, features, and risk
      factors of postoperative complications. RESULTS: During a median follow-up period
      of 671 days, 17 patients (4.7 %) developed postoperative complications, including
      bile duct injuries, intraabdominal abscess, wound infection, incisional hernia,
      paralytic ileus, and pneumonia. Reoperation was required in five patients (1.4
      %). Overall inpatient mortality occurred in one patient (0.3 %) who developed
      aspiration pneumonia. In multivariate stepwise regression analyses, poor physical
      status (American Society of Anesthesiologists score of >=3) and preoperative
      diagnosis of acute cholecystitis were identified as significant risk factors for
      the development of postoperative complications (P = 0.0009 and P = 0.04,
      respectively). CONCLUSIONS: These findings suggest that SILC is a relatively safe
      procedure with an acceptable postoperative complication rate but requires careful
      attention especially in patients with poor physical status and/or acute
      cholecystitis.

PMID- 25052127
TI  - Laparoscopic mobilization of the splenic flexure: the use of color-grading as a
      unique teaching tool.
AB  - This video shows submesocolic medial-to-lateral laparoscopic mobilization of the
      splenic flexure in which embryologically-derived planes are highlighted using
      colorized parts in a black and white background. The concept of traction and
      counter-traction is used to create a tissue "bridge" to work beneath, making
      efficient use of both of the surgeon's hands. To our knowledge, the color-grading
      technique has not been previously used to edit a video of a laparoscopic
      procedure, thus creating a new method of teaching.

PMID- 25052128
TI  - Efficacy of transanal tube for prevention of anastomotic leakage following
      laparoscopic low anterior resection for rectal cancers: a retrospective cohort
      study in a single institution.
AB  - BACKGROUND: Anastomotic leakage is one of the most serious complications
      following laparoscopic low anterior resection (LAR) for rectal cancers. The
      purpose of this study was to investigate whether transanal tube placement can
      reduce anastomotic leakage following laparoscopic LAR. METHODS: Retrospective
      assessment was performed on 205 patients with rectal cancers who underwent
      laparoscopic LAR. A transanal tube was placed after anastomosis in 96 patients
      (group A). Another 109 patients were operated on without a transanal tube (group
      B). Clinicopathological and operative variables, the frequencies of anastomotic
      leakage and re-operation after leakage were investigated. RESULTS: Patient age,
      gender, body mass index, tumor size, Dukes' stage, intra-operative blood loss,
      and the rate of left colic artery preservation were comparable between the two
      groups. Tumor location was lower and operative time was significantly longer in
      group A than group B (p < 0.001). Overall rate of leakage was 9.3 % (19/205). The
      frequency of leakage was 4.2 % (4/96) in group A and was 13.8 % (15/109) in group
      B. The rate of leakage was significantly lower in group A (p < 0.05).
      Furthermore, the re-operation rate for symptomatic anastomotic leakage was 0 %
      (0/4) in group A, while in contrast it was 73.3 % (10/15) in group B. The rate of
      re-operation was lower in group A than group B (p < 0.05) and all cases with
      symptomatic leakage in group A were cured by conservative treatment. CONCLUSIONS:
      Transanal tube placement was effective for prevention of anastomotic leakage
      following laparoscopic LAR and avoiding re-operation after symptomatic leakage.

PMID- 25052129
TI  - Laparoscopic resection for large gastric gastrointestinal stromal tumor (GIST):
      intermediate follow-up results.
AB  - BACKGROUND: Laparoscopic wedge resection has become a widely accepted treatment
      for small gastrointestinal stromal tumor (GIST) of the stomach. However, its
      feasibility as treatment for large gastric GIST is not known. In this
      retrospective study, the perioperative and oncologic outcomes of laparoscopic
      wedge resection for gastric GIST (5-8 cm) were reviewed. METHODS: Between
      November 2002 and December 2012, a total of 39 patients with primary gastric GIST
      sized 5-8 cm underwent surgery at a tertiary care center, including 18 patients
      who underwent laparoscopic wedge resection of the stomach (Lap group) and 21
      patients who underwent open wedge resection of the stomach (Open group).
      Clinicopathological parameters were reviewed and compared between the groups.
      RESULTS: The demographics including age, gender, and body weight were similar
      between groups. The operative outcomes including blood loss, hospital stay, and
      surgical complications were also similar, except that operative time was longer
      in the Lap group (146.6 +/- 50.2 vs. 113.3 +/- 42.9 min in the Open group, p =
      0.03). There was no tumor rupture, conversion of procedures, or major surgical
      morbidity in either group. The overall median follow-up time was 3.6 years (1.0
      11.1). Only one patient in the Lap group had liver metastasis (4 months
      postoperatively). This patient remains alive 5 years later under imatinib
      treatment. One patient in the Open group and three patients in the Lap group have
      died of GIST-unrelated diseases. CONCLUSIONS: Laparoscopic wedge resection of the
      stomach for primary gastric GIST (5-8 cm) appears to be safe and feasible, with
      operative and oncological outcomes comparable to those of the open method.

PMID- 25052130
TI  - The efficacy of cefazolin in reducing surgical site infection in laparoscopic
      cholecystectomy: a prospective randomized double-blind controlled trial.
AB  - BACKGROUND: A prophylactic antibiotic is recommended in open cholecystectomy
      surgeries, but in laparoscopic cholecystectomies such prophylaxis is
      controversial. Recent reviews have not found conclusive evidence that routine
      prophylaxis, especially in low risk patients, is effective. This clinical trial
      was undertaken to evaluate the efficacy of cefazolin in reducing surgical site
      infection SSI in laparoscopic cholecystectomies in a sample not screened for high
      or low risk patients. METHODS: A randomized double-blind controlled trial was
      conducted in a single university hospital. Scheduled cholecystectomy patients
      without selection for patient risk factors were randomized into two groups. Pre
      operatively, group A patients received a placebo of 10 ml isotonic sodium
      chloride, and group B patients received 1 g of cefazolin as a prophylactic
      antibiotic. All patients underwent a standard laparoscopic cholecystectomy, and
      were followed up for at least 30 days. RESULTS: Two hundred ninety-nine patients
      were randomized (149 in group A and 150 in group B). SSI occurred in seven
      patients (2.34 %), five (1.67 %) in the placebo group, and two (0.67 %) in the
      prophylactic antibiotic group. The difference was not statistically significant
      (p value = 0.512), and no specific risk factors for post-operative infection were
      identified. CONCLUSIONS: A single dose of preoperative prophylactic cefazolin has
      no significant benefit in reducing the incidence of SSI in laparoscopic
      cholecystectomy. Whether or not to use a prophylactic depends on the individual
      patient, and the consideration of the attending surgeon.

PMID- 25052131
TI  - Preface: Forum on new materials and approaches for electrochemical storage.

PMID- 25052132
TI  - Neurological events after liver transplantation: a single-center experience.
AB  - The aim of this study was to identify potential risk factors linked to neurologic
      events (NE) occurring after liver transplantation (LT) and use them to construct
      a model to predict such events. From odds ratios (OR) of risk factors, a scoring
      system was assessed using multivariate regression analysis. Forty-one of 307 LT
      patients presented NE (13.3%), with prolonged hospital stay and decreased post-LT
      survival. On multivariate analysis, factors associated with NE included: severe
      pre-LT ascites OR 3.9 (1.80-8.41; P = 0.001), delta sodium >=12 mEq/l OR 3.5
      (1.36-8.67; P = 0.01), and post-LT hypomagnesemia OR 2.9 (1.37-5.98; P = 0.005).
      Points were assigned depending on ORs as follows: ascites 4 points, and
      hypomagnesemia and delta sodium >=12 mEq/l, 3 points each (score range = 0-10
      points). ROC curve analysis suggested good discriminative power for the model,
      with a c-statistic of 0.72 (CI 0.62-0.81; P < 0.0001), best performance for a
      cutoff value >3 points (71% sensitivity, 60% specificity). NE risk increased
      progressively from 6.4%, to 10.3%, 12.8%, 31.5% and 71.0% as scores rose from 0
      to 3, 4, 6-7 and 10 cumulative points, respectively. The score described helps to
      identify patients potentially at risk for neurologic events, and its prevention
      would decrease morbidity and mortality after LT. 

PMID- 25052133
TI  - Creep loading during degradation attenuates mechanical property loss in PLGA.
AB  - While absorbable materials and medical devices primarily degrade through
      hydrolysis, their degradation kinetics are sensitive to environmental conditions,
      including temperature, pH, and mechanical loading. While there is some consistent
      information in the literature suggesting that strain controlled loading
      accelerates strength loss, there is much more limited information on the
      interaction between degradation and mechanical load applied under force control.
      Force control conditions impose a different stress state on the material and
      therefore, may exhibit different effects on degradation. In this study, the
      interaction between loading and degradation rate for an exemplary absorbable
      polymer, poly(l-lactide-co-glycolide), was investigated. The results indicated
      that load during degradation results in significant polymer creep, which is
      associated with increased force loss, but decreased strength loss (i.e., stress
      based parameters such as ultimate stress). This study further identified that
      changes to the degradation kinetics from exposure to loading were not associated
      with alterations to polymer crystallinity but were associated with delayed loss
      of molecular weight. Overall, these results demonstrate the importance of
      investigating the interaction between loading and degradation and that physical
      changes, such as those induced by creep, rather than chemical changes offer the
      strongest explanation for alteration of degradation kinetics.

PMID- 25052134
TI  - Assessment overload?

PMID- 25052135
TI  - Analysis of the Vitellogenin gene of rice moth, Corcyra cephalonica Stainton.
AB  - Vitellogenin (Vg) is a precursor of the major yolk protein, an essential nutrient
      for the embryonic development of oviparous animals including insects. Here, the
      gene(CceVg [Corcyra cephalonica Vg] ) encoding the Vg (CceVg of moth, C.
      cephalonica, was cloned and sequenced. The gene sequence was 6,721-bp long and
      contained 5five introns and six exons that together formed a 5,382-bp open
      reading frame. The deduced protein (CceVg) consisted of 1,793 amino acid
      residues, including a 16-amino-acid signal peptide. The putative molecular weight
      of the primary Vg protein was 202.46 kDa. The CceVg contained all conserved
      domains and motifs that were commonly found in most insect Vgs except the
      presence of a polyserine tract at the C-terminal region, which had not been
      reported in other lepidopteran Vgs. The expression pattern showed that CceVg was
      first transcribed at a very low level in the early larval stage but disappeared
      in later stage larva. In female, the CceVg mRNA was detected in early pupal stage
      and throughout adult stage. Interestingly, the CceVg mRNA was detected only in
      mated males at low levels, not in the virgin ones. Injection of CceVg double
      stranded RNA into early-emergent females caused severely abnormal ovaries.

PMID- 25052137
TI  - Statistical shape and appearance models for fast and automated estimation of
      proximal femur fracture load using 2D finite element models.
AB  - Estimating the risk of osteoporotic fractures is an important diagnostic step
      that needs to be taken before medicinal treatment. Densitometry-based criteria
      are normally used in clinical practice for this purpose. However, densitometry
      based techniques could not explain all low-energy fractures. As patient-specific
      finite element (FE) models allow for consideration of other parameters (e.g. load
      conditions) that are known to be associated with fracture, they are considered
      promising candidates for more accurate fracture risk estimation. Nevertheless,
      they are often time consuming, expensive, and complex to build and may need the
      type of expertise that is not normally available in clinical settings. In this
      study, we report the development of an automated platform for estimating proximal
      femur fracture loads using patient-specific 2D FE models generated using dual
      energy x-ray absorptiometry (DXA) scans. First, a statistical shape and
      appearance model (SSAM) is built using DXA scans of patients screened for
      osteoporosis following a low energy fracture. SSAM is then used together with
      Active Appearance Models (AAM) for automated segmentation of the proximal femur
      from new unseen DXA scans. The mean point-to-curve error of the automated
      procedure, i.e. 1.2-1.4mm, is shown to be only slightly larger than the intra
      observer variability of manual segmentation, i.e. 1.0mm. Moreover, the developed
      platform automatically meshes the segmented shape, assigns density-based
      mechanical properties, assigns loads and boundary conditions, submits the 2D FE
      model for solution, and performs post-processing of the 2D FE simulation data to
      determine fracture loads. The fracture loads predicted using the manually
      generated and automatically generated 2D FE models are shown to be very close
      with a mean difference of around 8.8%. Repeated measures ANOVA showed no
      significant differences between the fracture loads calculated using FE models
      manually generated by three independent observers and those calculated using the
      automatically generated FE models (p>0.05). 

PMID- 25052136
TI  - Health-related quality of life and emotional distress in patients with dizziness:
      a cross-sectional approach to disentangle their relationship.
AB  - BACKGROUND: Dizziness is frequently encountered in medical practice, often takes
      a chronic course and can impair the health related quality of life (HRQoL).
      However results on the extent of this impairment of HRQoL are mixed. Furthermore,
      the relationship between dizziness and the HRQoL is only partially understood.
      The role of clinical symptoms of dizziness and psychosocial factors such as
      emotional distress on this relationship is for the most part unknown. METHODS:
      The cross-sectional study evaluated the HRQoL in 203 patients suffering from
      dizziness, using the Medical Outcomes Studies 36-Item Short-Form Health-Survey
      (SF-36). The results were correlated with the severity of dizziness, using the
      Dizziness Handicap-Inventory (DHI), with emotional distress, using the Hospital
      Anxiety and Depression-Scale (HADS) and with further clinical symptoms and
      psychosocial parameters. In a multivariate hierarchical regression analysis
      associated variables which explain significant variance of the mental and
      physical HRQoL (MCS-36, PCS-36) were identified. RESULTS: Patients suffering from
      dizziness showed a markedly reduced mental and physical HRQoL. Higher DHI and
      HADS scores were correlated with lower MCS-36 and PCS-36 scores. Taken together
      DHI and vertigo characteristics of dizziness explained 38% of the variance of PCS
      36. Overall explained variance of PCS-36 was 45%. HADS and living with a
      significant other explained 66% of the variance of MCS-36 (overall variance
      explained: 69%). CONCLUSION: Both the physical and mental HRQoL are significantly
      impaired in patients with dizziness. While the impairment in PCS-36 can be
      explained by clinical symptoms of the dizziness, MCS-36 impairment is largely
      associated with psychosocial factors. To improve the patient's overall well-being
      significantly and permanently doctors have to keep in mind both, the clinical
      symptoms and the psychosocial factors. Therefore, in addition to the physical
      examination doctors should integrate a basic psychological examination into the
      daily routine with dizziness patients.

PMID- 25052138
TI  - Financial hardship and the intensity of medical care received near death.
AB  - BACKGROUND: Although end-of-life (EOL) care can present a substantial financial
      burden for the household, the influence of this burden on the intensity of care
      received at the EOL remains unknown. The goal of this study was to determine the
      association between financial hardship and intensive care in the last week of
      life. METHODS: The Coping with Cancer (CwC) Study is a longitudinal, multisite
      cohort study of terminally ill cancer patients and their informal caregivers,
      September 2002-February 2008. Patients (N = 281) were followed from baseline to
      death, a median of 4.4 months after baseline assessment. Intensive care was
      defined as the use of resuscitation and/or ventilation in the patient's last week
      of life. Financial hardship was measured at study baseline as a positive response
      to whether the household had to use all or most of their savings because of the
      family member's illness. RESULTS: Twenty-nine percent reported financial
      hardship, and 9% received intensive EOL care. Patients reporting financial
      hardship had a 3.22 (95% CI: 1.38, 7.53) higher likelihood of receiving intensive
      EOL care compared with patients not reporting financial hardship. After adjusting
      for sociodemographic characteristics and patient preferences, patients reporting
      financial hardship had a 3.05 (95% CI: 1.22, 7.62) higher likelihood of receiving
      intensive EOL care. CONCLUSION: The depletion of a family's financial resources
      is a significant predictor of intensive EOL care, over and above the influence of
      sociodemographic characteristics and patient preferences.

PMID- 25052141
TI  - An ider(17)(q10)t(15;17) with spliced long-type PML-RARA fusion transcripts in a
      case of acute promyelocytic leukemia.
AB  - The ider(17)(q10)t(15;17) is a relatively rare chromosomal rearrangement in acute
      promyelocytic leukemia patients. We describe herein a case of APL with a poor
      prognosis and ider(17)(q10)t(15;17)(q22;q12), which was confirmed by fluorescence
      in situ hybridization. Reverse transcription polymerase chain reaction (RT-PCR)
      and sequencing of PCR products were used to detect the PML-RARA fusion gene and
      delineate the sequence of the fusion transcripts. We found that the PML-RARA
      fusion gene of this patient was the long isoform, which only generated
      transcripts of a splice variant lacking PML exon 5 and a splice variant lacking
      PML exons 5 and 6. Although the clinical and prognostic significance of patients
      with an ider(17)(q10)t(15;17) remains unclear, a combination of cytogenetics and
      molecular biology analysis should be performed to obtain further information
      about this chromosomal abnormality.

PMID- 25052142
TI  - A gene signature for a long-term survivor of an atypical teratoid/rhabdoid tumor.
AB  - Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors that are
      commonly associated with a dismal prognosis. However, there have been isolated
      reports of long-term survival that was not necessarily correlated with other
      prognostic factors such as age, clinical stage, or extent of surgical resection.
      Here, we report the case of a 6-year-old boy with AT/RT who remained disease-free
      for 8 years after undergoing subtotal surgical resection followed only by
      radiation therapy. On recurrence, the tumor rapidly progressed, leading to the
      patient's death a short time later. To further characterize this case and learn
      more about the tumor biology of long-term survivors, we compared the gene
      expression (GE) profiles from representative samples obtained from primary,
      recurrent, and progressive disease tumors of the above-mentioned patient along
      with a cohort of primary untreated AT/RT samples using cDNA microarrays. Global
      GE analysis and unsupervised hierarchical clustering showed the three events
      clustered together and distinctly apart from the rest of the samples. This
      indicates a GE background that is maintained throughout the course of the
      disease. This unique case suggests that there may be specific clinical
      characteristics associated with distinctive molecular subtypes of AT/RT. The
      identification and characterization of AT/RT subtypes could lead to advances in
      both prognosis and treatment of these tumors. 

PMID- 25052143
TI  - A host as an ecosystem: Wolbachia coping with environmental constraints.
AB  - The Wolbachia are intracellular endosymbionts widely distributed among
      invertebrates. These primarily vertically transmitted alpha-proteobacteria have
      been intensively studied during the last decades because of their intriguing
      interactions with hosts, ranging from reproductive manipulations to mutualism. To
      optimize their vertical transmission from mother to offspring, the Wolbachia have
      developed fine-tuned strategies. However, the Wolbachia are not restricted to the
      female gonads and frequently exhibit wide intra-host distributions. This
      extensive colonization of somatic organs might be necessary for Wolbachia to
      develop their diverse extended phenotypes. From an endosymbiont's perspective,
      the within-host environment potentially presents different environmental
      constraints. Hence, the Wolbachia have to face different intracellular habitats,
      their host's immune system as well as other microorganisms co-occurring in the
      same host individual and sometimes even in the same cell. A means for the
      Wolbachia to protect themselves from these environmental constraints may be to
      live 'hidden' in vacuoles within host cells. In this review, we summarize the
      current knowledge regarding the extent of the Wolbachia pandemic and discuss the
      various environmental constraints these bacteria may have to face within their
      'host ecosystem'. Finally, we identify new avenues for future research to better
      understand the complexity of Wolbachia's interactions with their intracellular
      environment. 

PMID- 25052144
TI  - Comparison of the biological properties of ProRoot MTA, OrthoMTA, and Endocem MTA
      cements.
AB  - INTRODUCTION: OrthoMTA (BioMTA, Seoul, Korea) and Endocem MTA (Maruchi, Wonju-si,
      Korea) were recently developed to overcome the disadvantages of ProRoot MTA
      (Dentsply, Tulsa, OK). This study aimed to compare the biological properties of
      OrthoMTA and Endocem MTA with those of ProRoot MTA using the preosteoblastlike
      cell line MC3T3-E1. METHODS: The setting times of calcium silicate-based cements
      (CSCs) and their effects on the pH of distilled water during storage were
      determined according to ISO standards. MC3T3-E1 cells were cultured with ProRoot
      MTA, OrthoMTA, and Endocem MTA. The viability of the cells was assessed using the
      Cell Counting Kit-8 assay (Dojindo Laboratory, Kumamoto, Japan) on the
      supernatants of CSCs, and the cells' osteopontin production was determined by an
      enzyme-linked immunosorbent assay on a culture with the materials on days 3 and 7
      of incubation. RESULTS: Endocem MTA exhibited a significantly shorter setting
      time (15.3 +/- 0.5 minutes) than did ProRoot MTA and OrthoMTA (318.0 +/- 56.0 and
      324.3 +/- 2.1 minutes, P < .05). Additionally, all CSCs caused their storage
      water to become highly alkaline after 7 days. OrthoMTA was significantly more
      cytotoxic than ProRoot and Endocem MTA (P < .05). ProRoot MTA induced
      significantly more OPN production than OrthoMTA and Endocem MTA on both days 3
      and 7 (P < .05). CONCLUSIONS: ProRoot MTA appeared to be superior to OrthoMTA and
      Endocem MTA in terms of biological properties although Endocem MTA exhibited the
      shortest setting time and presented lower cytotoxicity with osteoblastlike cells.

PMID- 25052145
TI  - Treatment outcome of the teeth with cemental tears.
AB  - INTRODUCTION: A cemental tear is a special type of surface root fracture noted in
      combination with periodontal and/or periapical bony destruction. We hypothesized
      that clinical characteristics and treatment techniques may affect the prognosis
      of teeth with cemental tears. METHODS: Treatment outcome for the teeth with a
      cemental tear was assessed in a multicenter cemental tear study project. Of the
      71 teeth with cemental tears, 38 teeth (53.5%) were extracted. The remaining 33
      teeth (46.5%) were examined for a treatment outcome of healed, questionable, or
      failed. RESULTS: Outcome assessment found that 51.5% (17/33), 42.4% (14/33), and
      6.1% (2/33) of teeth were classified as healed, questionable, and failed,
      respectively. Additive bivariate analysis indicated a significant difference
      between treatment outcome and the length (P = .01) and apicocoronal location (P =
      .02) of the separated root fragments. Logistic regression analysis found that
      treatment technique and apicocoronal location of cemental tears may affect the
      treatment outcome. The percentage of healed cemental tear cases located in the
      apical, middle, and cervical third of roots was 11.1%, 66.7%, and 60.0%,
      respectively. By surgical management, 57.7% of cemental tears were healed,
      whereas only 28.6% cases were healed after nonsurgical treatment. CONCLUSIONS:
      Most teeth with cemental tears can be retained to function by nonsurgical and
      surgical periodontal and endodontic treatment. Clinical diagnosis and treatment
      of cemental tears should also consider the apicocoronal location and the type of
      treatment technique to improve outcomes.

PMID- 25052146
TI  - Comparative evaluation of canal isthmus debridement efficacy of modified EndoVac
      technique with different irrigation systems.
AB  - INTRODUCTION: The purpose of this study was to evaluate the canal isthmus
      debridement efficacy of a new modified EndoVac (Discus Dental, Culver City, CA)
      irrigation protocol in comparison with EndoVac, passive ultrasonic irrigation
      (PUI), and conventional needle irrigation in mesial roots of mandibular molars.
      METHODS: The mesial roots of 64 extracted mandibular molars mounted in resin
      using Kuttler's endodontic cube, sectioned at 2 and 4 mm from the working length,
      were randomly divided into 4 groups (n = 16): group 1: Max-I-Probe (Dentsply
      Tulsa Dental, York, PA), group 2: EndoVac (EVI), group 3: modified EndoVac, and
      group 4: PUI. The specimens were reassembled and instrumented. A standard
      irrigation protocol was used during cleaning and shaping and final irrigation
      with the 4 irrigation/agitation techniques. Images of the isthmus region were
      taken before and after cleaning and shaping and after final irrigation. The
      percentage reduction of debris in the isthmus region was calculated by using the
      software program Image J (v1.43; National Institutes of Health, Bethesda, MD).
      Intergroup analysis was performed using the Kruskal Wallis and Mann-Whitney U
      tests. Intragroup analysis was performed using Friedman and Wilcoxon signed rank
      tests. The level of significance was set at P < .05. RESULTS: Intragroup analysis
      revealed a statistically significant difference in the percentage reduction of
      debris after cleaning and shaping and after final irrigation protocol in all the
      groups (P < .001). The final irrigation protocol produced significantly cleaner
      canal isthmuses in all the groups (P < .001). On intergroup analysis, the
      modified EVI group performed significantly better than the other groups. The EVI
      and PUI groups performed better than the Max-I-Probe group. There was no
      statistical significance between the EVI and PUI groups. CONCLUSIONS: Canal
      isthmuses were significantly cleaner with the modified EndoVac irrigation
      technique when compared with the cleanliness seen with the other irrigation
      systems.

PMID- 25052147
TI  - Postcricoid carcinoma: is organ preservation justified in T3?
AB  - INTRODUCTION: Postcricoid carcinoma in India, is seen especially in middle-aged
      females. Surgical treatment for postcricoid carcinoma has reduced because of
      increased organ-preserving nonsurgical strategies. Surgical intervention leads to
      morbidity in the form of laryngectomy. OBJECTIVES/HYPOTHESIS: To study the
      outcomes of nonsurgical management and to assess whether organ preservation is
      justified or if radical surgery should be the first line of management for T3
      postcricoid carcinoma. STUDY DESIGN/METHODS: This retrospective study analyzed 59
      patients with T3 postcricoid carcinoma who were treated with nonsurgical modality
      in the form of radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). End
      points studied were locoregional control, disease-free survival (DFS), and
      overall survival. We also observed feeding tube and tracheostomy tube dependency.
      RESULTS: Locoregional control rate, DFS rate, and overall survival at the end of
      2 years were 8.98%, 8.59%, and 15.71% respectively. Seventeen and 12 patients of
      the study population were dependent on nasogastric tube and tracheostomy tube,
      respectively, until their last follow-up. CONCLUSION: Results of organ
      preservation with radical RT or CCRT do not show promising outcomes in the
      locally advanced T3 carcinoma of postcricoid. Radical surgery with appropriate
      reconstruction and postoperative radiotherapy is probably better in terms of
      local control as well as overall survival. Proper preoperative counseling and
      postoperative rehabilitation of speech and stoma can improve the quality of life
      of T3 postcricoid carcinoma patients. LEVEL OF EVIDENCE: 4.

PMID- 25052148
TI  - Henoch-Schonlein purpura in two pediatric patients presenting as terminal
      ileitis.

PMID- 25052149
TI  - Elevation of PRKCDBP, a novel transcriptional target of TNF-alpha, and its
      downregulation by infliximab in patients with ulcerative colitis.
AB  - BACKGROUND: Protein kinase C delta binding protein (PRKCDBP/Cavin3/hSRBC) is a
      putative tumor suppressor that is downregulated in many human cancers. Recently,
      PRKCDBP was identified to be activated by nuclear factor-kappaB in response to
      tumor necrosis factor (TNF)-alpha. AIMS: To explore the potential of PRKCDBP as a
      diagnostic or prognostic marker for inflammatory bowel disease, the possible
      correlation between its expression status and TNF-alpha signaling was evaluated
      in ulcerative colitis (UC) patients, both pre- and post-infliximab (IFX) therapy.
      METHODS: In total, 31 IFX therapy-naive patients (13 females; median age, 41
      years) with moderate-to-severe UC who had been scheduled for IFX treatment were
      included. Immunohistochemical analysis of TNF-alpha and PRKCDBP expression was
      performed in rectal biopsies. RESULTS: A significant correlation was observed in
      immunoreactivity between TNF-alpha and PRKCDBP. IFX therapy reduced
      immunohistochemical expression of PRKCDBP and TNF-alpha (P < 0.001 and P = 0.005,
      respectively). The mean PRKCDBP expression level decreased from 54.5 to 30.2%,
      and that of TNF-alpha decreased from 54.5 to 36.2%. The immunohistochemical
      expression pre- and post-PRKCDBP therapy correlated significantly with TNF-alpha
      levels pre- and post-therapy (Spearman's rank correlation test; P = 0.005 and P =
      0.001, respectively). CONCLUSIONS: These results demonstrate that mucosal
      expression of PRKCDBP correlated strongly with TNF-alpha expression in UC
      patients and that IFX therapy resulted in profound reductions in both PRKCDBP and
      TNF-alpha. Thus, these findings support that PRKCDBP expression is tightly
      controlled by TNF-alpha, and the anti-inflammatory effect of IFX may in part stem
      from blockade of the TNF-alpha-PRKCDBP signaling pathway.

PMID- 25052150
TI  - Intestinal microbiota transplantation, a simple and effective treatment for
      severe and refractory Clostridium difficile infection.
AB  - BACKGROUND: Restoring normal fecal flora through intestinal microbiota
      transplantation (IMT) was successful in curing recurrent Clostridium difficile
      infection (CDI). However, only a few cases have been reported of IMT being
      utilized for the treatment of severe or fulminant CDI. AIM: Is IMT a simple and
      effective treatment for severe and recurrent CDI? METHODS: In this retrospective
      study, we report 14 patients with severe CDI refractory to conventional medical
      therapy, who underwent IMT. Fresh donor stool specimen was manually homogenized
      with warm tap water, filtered through gauze and then instilled through
      nasogastric tube (NGT). The primary outcome was clinical cure, defined as less
      than 3 loose bowel movements a day on day 7 after IMT and no need for further CDI
      therapy. The secondary outcomes were recurrence of CDI within 100 days of IMT and
      30-day mortality after IMT. Descriptive statistics were done. RESULTS: Fourteen
      patients with severe and refractory CDI received IMT. Mean age was 73.4 +/- 11.9
      years (range 52-92). IMT was given via NGT in 13 of the 14 patients. Eleven
      patients (79 %) achieved cure after IMT. No recurrence was seen in the patients
      who responded to IMT and were alive within the 100 day follow-up period. IMT was
      well tolerated. The 30-day all-cause mortality was 29 %, all 4 patients died as a
      result of their underlying cancer. No patients died as a result of CDI or IMT.
      CONCLUSIONS: IMT performed at the bedside via NGT is effective and safe for the
      treatment of severe and refractory CDI, and prevents recurrence.

PMID- 25052151
TI  - The Pre-Anschluss Vienna School of Medicine - The medical scientists: Karl
      Landsteiner (1868-1943) and Otto Loewi (1873-1961).
AB  - Two famous medical scientists are described whose major advances were made
      largely from laboratory-based research. Karl Landsteiner, who received the Nobel
      Prize in 1930, was the discoverer or co-discoverer of the blood groups and the
      Rhesus factor. He contributed to the understanding of poliomyelitis, syphilis and
      typhus. He made major contributions to immunology, inter alia by isolating
      haptens. After World War I, he left Austria and continued his work initially in
      the Netherlands and then at the Rockefeller Institute in the USA. Otto Loewi, a
      pharmacologist, received his Nobel Prize (jointly with his life-long friend, Sir
      Henry Dale) in 1936 for his discovery that acetylcholine was the chemical agent
      for the stimulation of autonomic nerves to transmit to the organs they govern. He
      also made numerous other contributions including the demonstration that amino
      acids could be converted by animals to proteins. He left Austria after the
      Anschluss and settled in the USA. 

PMID- 25052152
TI  - The pre-Anschluss Vienna School of Medicine - the physicians: Sigmund Freud (1856
      1939), Julius Wagner-Jauregg (1857-1940) and Karel Wenckebach (1864-1940).
AB  - Three physicians are discussed. Sigmund Freud, probably the best-known member of
      the Vienna School of Medicine, was the path-breaking pioneer in psychoanalysis
      and psychotherapy. Julius Wagner-Jauregg was a psychiatrist who discovered the
      link between iodine deficiency and goitre and also developed malaria therapy to
      treat progressive paralysis caused by syphilis for which he was awarded the Nobel
      Prize. Karel Wenckebach, the pioneering Dutch cardiologist, is best known for the
      Wenckebach block. After the Anschluss, fate dealt very different hands to these
      three physicians. Freud fled to London where he soon died. Wagner-Jauregg, who
      had some pan-Germanic sympathies as well as views on eugenics, left a
      controversial legacy. The Dutch cardiologist Wenckebach died in Vienna shortly
      after his homeland had been invaded in 1940 by that of his hosts. 

PMID- 25052153
TI  - The Pre-Anschluss Vienna School of Medicine--The surgeons: Ignaz Semmelweis (1818
      1865), Theodor Billroth (1829-1894) and Robert Barany (1876-1936).
AB  - A brief history of the Vienna School of Medicine is sketched out from its
      founding in the mid-18th century by Gerard van Swieten until the Anschluss in
      March 1938. The pioneering work of Ignaz Semmelweis on the causes and the
      prevention of puerperal fever is discussed. This is followed by ground-breaking
      innovations, particularly in abdominal surgery, by Theodor Billroth and by Robert
      Barany's Nobel Prize winning work inter alia on defining the pathology and
      physiology of the human vestibular apparatus. The lives and work of these three
      outstanding medical practitioners are described, together with their successes
      and failures. Only Billroth's achievements were appreciated in Vienna during
      their lifetimes. Semmelweis' work was belittled during his lifetime and he died
      obscurely in a mental institution. Barany had to immigrate to Sweden to achieve
      recognition. 

PMID- 25052154
TI  - Sox5 and chromatophores: switching pigment cell fates.

PMID- 25052155
TI  - Redesigning the exploitation of wheat genetic resources.
AB  - More than half a million wheat genetic resources are resting in gene banks
      worldwide. Unlocking their hidden favorable genetic diversity for breeding is
      pivotal for enhancing grain yield potential, and averting future food shortages.
      Here, we propose exploiting recent advances in hybrid wheat technology to uncover
      the masked breeding values of wheat genetic resources. The gathered phenotypic
      information will enable a targeted choice of accessions with high value for pre
      breeding among this plethora of genetic resources. We intend to provoke a
      paradigm shift in pre-breeding strategies for grain yield, moving away from
      allele mining toward genome-wide selection to bridge the yield gap between
      genetic resources and elite breeding pools. 

PMID- 25052156
TI  - Factors related to delays in pre-hospital management of status epilepticus.
AB  - INTRODUCTION: This study was designed to identify factors related to delays in
      pre-hospital management of status epilepticus (SE). METHODS: This retrospective
      study includes all adult (>16 years of age) patients (N = 82) diagnosed with
      established SE in the Helsinki University Central Hospital emergency department
      (ED) over 2 years. SE was defined as a clinically observed episode fulfilling one
      of the following criteria: (1) continuous seizure lasting over 30 min; (2)
      recurring seizures without return of consciousness between seizures; (3)
      occurrence of more than four seizures within any 1 h. We collected 15 variables
      related to SE type, patient, and SE episode from the medical records, defined and
      calculated six pre-hospital delay parameters and analyzed their relations using
      univariate analysis and multivariate linear regression models. RESULTS: In the
      multivariate regression analysis, the focal SE was significantly associated with
      a long delay from SE onset to initial treatment (p < 0.05), to diagnosis (p <
      0.002), and to anesthesia (p < 0.002). Administration of the initial treatment
      before emergency medical service arrived was significantly associated with long
      delay of the first alarm (p < 0.02) and arrival at the first ED (p < 0.04).
      Primary admission to a healthcare unit other than tertiary hospital caused a
      significant delay in diagnosis (p < 0.008) and anesthesia (p < 0.02).
      Surprisingly, univariate analysis revealed that if the SE onset occurred in a
      healthcare unit, the delays from SE onset to first alarm (p < 0.001), to arrival
      in first ED (p < 0.001), to arrival in tertiary hospital (p < 0.001), to
      diagnosis (p < 0.02), and to anesthesia (p < 0.01) were significantly longer than
      in cases in which SE onset occurred at a public place. CONCLUSION: We found
      remarkable inadequacy in recognition of SE both among laity and medical
      professionals. There is an obvious need for increasing awareness of imminent SE
      and optimizing the pre-hospital management of established SE. SE should be
      considered as a medical emergency comparable with stroke and cardiac infarction
      and be allocated with similar resources in the pre-hospital management.

PMID- 25052157
TI  - Traumatic brain injury associated coagulopathy.
AB  - BACKGROUND: The presence of coagulopathy is common after severe trauma. The aim
      of this study was to identify whether isolated severe traumatic brain injury
      (TBI) is an independent risk factor for coagulopathy. METHODS: Prospective
      observational cohort of adult patients admitted to a Level I Trauma Center within
      6 h of injury. Patients were categorized according to the abbreviated injury
      scale (AIS): Group 1-isolated severe TBI (AIS head >= 3 + AIS non-head < 3);
      Group 2-severe multisystem trauma associated with severe TBI (AIS head >= 3 + AIS
      non-head >= 3); Group 3-severe multisystem trauma without TBI (AIS head < 3 + AIS
      non-head >= 3). Primary outcome was the development of coagulopathy. Secondary
      outcome was in-hospital mortality. RESULTS: Three hundred and forty five patients
      were included (Group 1 = 48 patients, Group 2 = 137, and Group 3 = 160). Group 1
      patients had the lowest incidence of coagulopathy and disseminated intravascular
      coagulopathy, and in general presented with better coagulation profile measured
      by either classic coagulation tests, thromboelastography or clotting factors.
      Isolated severe TBI was not an independent risk factor for the development of
      coagulopathy (OR 1.06; 0.35-3.22 CI, p = 0.92), however, isolated severe TBI
      patients who developed coagulopathy had higher mortality rates than isolated
      severe TBI patients without coagulopathy (66 vs. 16.6 %, p < 0.05). The presence
      of coagulopathy (OR 5.61; 2.65-11.86 CI, p < 0.0001) and isolated severe TBI (OR
      11.51; 3.9-34.2 CI, p < 0.0001) were independent risk factors for in-hospital
      mortality. CONCLUSION: Isolated severe TBI is not an independent risk factor for
      the development of coagulopathy. However, severe TBI patients who develop
      coagulopathy have extremely high mortality rates.

PMID- 25052158
TI  - Perihemorrhagic ischemia occurs in a volume-dependent manner as assessed by
      multimodal cerebral monitoring in a porcine model of intracerebral hemorrhage.
AB  - BACKGROUND: Changes in the perihemorrhagic zone (PHZ) of intracerebral hemorrhage
      (ICH) are variable. Different mechanisms contribute to secondary neuronal injury
      after ICH. This multimodal monitoring study investigated early changes in the PHZ
      of ICH. METHODS: Twenty-four swine were anesthetized, ventilated, and underwent
      monitoring of vital parameters. Next to an intracranial pressure-probe (ICP),
      microdialysis (MD), thermodiffusion cerebral blood flow (td-CBF), and oxygen
      probes (PbrO2) were placed into the gray white matter junction for 12 h of
      monitoring. ICH was induced using the autologous blood injection model. Pre
      defined volumes were 0 ml (sham), 1.5 ml ipsilateral (1.5 ml), 3.0 ml ipsilateral
      (3.0 ml), and 3.0 ml contralateral (3.0 ml contra). RESULTS: ICP equally
      increased in all groups after ICH. In the 3.0 ml group tissue oxygenation
      decreased to ischemic values of 9 +/- 7 mmHg early after 6 h of monitoring. This
      decrease was associated with a significant perfusion reduction from 36 +/- 8
      ml/100 g/min to 20 +/- 10 ml/100 g/min. MD correlated with a threefold
      lactate/pyruvate ratio increase. Measurements in all other groups were unchanged.
      CONCLUSION: Multimodal monitoring demonstrates volume-dependent changes of tissue
      oxygenation, blood flow, and ischemic MD markers in the PHZ independent of
      increased ICP suggesting early moderate ischemia. No evidence was found for the
      existence of a perihemorrhagic ischemia in the small hematoma groups.

PMID- 25052159
TI  - Biomarkers improve clinical outcome predictors of mortality following non
      penetrating severe traumatic brain injury.
AB  - OBJECTIVE: This study assessed whether early levels of biomarkers measured in CSF
      within 24-h of severe TBI would improve the clinical prediction of 6-months
      mortality. METHODS: This prospective study conducted at two Level 1 Trauma
      Centers enrolled adults with severe TBI (GCS <=8) requiring a ventriculostomy as
      well as control subjects. Ventricular CSF was sampled within 24-h of injury and
      analyzed for seven candidate biomarkers (UCH-L1, MAP-2, SBDP150, SBDP145,
      SBDP120, MBP, and S100B). The International Mission on Prognosis and Analysis of
      Clinical Trials in TBI (IMPACT) scores (Core, Extended, and Lab) were calculated
      for each patient to determine risk of 6-months mortality. The IMPACT models and
      biomarkers were assessed alone and in combination. RESULTS: There were 152
      patients enrolled, 131 TBI patients and 21 control patients. Thirty six (27 %)
      patients did not survive to 6 months. Biomarkers were all significantly elevated
      in TBI versus controls (p < 0.001). Peak levels of UCH-L1, SBDP145, MAP-2, and
      MBP were significantly higher in non-survivors (p < 0.05). Of the seven
      biomarkers measured at 12-h post-injury MAP-2 (p = 0.004), UCH-L1 (p = 0.024),
      and MBP (p = 0.037) had significant unadjusted hazard ratios. Of the seven
      biomarkers measured at the earliest time within 24-h, MAP-2 (p = 0.002), UCH-L1
      (p = 0.016), MBP (p = 0.021), and SBDP145 (0.029) had the most significant
      elevations. When the IMPACT Extended Model was combined with the biomarkers, MAP
      2 contributed most significantly to the survival models with sensitivities of 97
      100 %. CONCLUSIONS: These data suggest that early levels of MAP-2 in combination
      with clinical data provide enhanced prognostic capabilities for mortality at 6
      months.

PMID- 25052160
TI  - Prostacyclin influences the pressure reactivity in patients with severe traumatic
      brain injury treated with an ICP-targeted therapy.
AB  - BACKGROUND: This prospective consecutive double-blinded randomized study
      investigated the effect of prostacyclin on pressure reactivity (PR) in severe
      traumatic brain injured patients. Other aims were to describe PR over time and
      its relation to outcome. METHODS: Blunt head trauma patients, Glasgow coma scale
      <=8, age 15-70 years were included and randomized to prostacyclin treatment (n =
      23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome
      scale (GOSE) at 3 months. PR was calculated as the regression coefficient between
      the hourly mean values of ICP versus MAP. Pressure active/stable was defined as
      PR <=0. RESULTS: Mean PR over 96 h (PRtot) was 0.077 +/- 0.168, in the
      prostacyclin group 0.030 +/- 0.153 and in the placebo group 0.120 +/- 0.173 (p <
      0.02). There was a larger portion of pressure-active/stable patients in the
      prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes
      over time were common. PRtot correlated negatively with GOSE score (p < 0.04).
      PRtot was 0.117 +/- 0.182 in the unfavorable (GOSE 1-4) and 0.029 +/- 0.140 in
      the favorable outcome group (GOSE 5-8). Area under the curve for prediction of
      death (ROC) was 0.742 and for favorable outcome 0.628. CONCLUSIONS: Prostacyclin
      influenced the PR in a direction of increased pressure stability and a lower
      PRtot was associated with improved outcome. The individual PR varied
      substantially over time. The predictive value of PRtot for outcome was not solid
      enough to be used in the clinical situation.

PMID- 25052161
TI  - Chinese medicine combined with calcipotriol betamethasone and calcipotriol
      ointment for Psoriasis vulgaris (CMCBCOP): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Psoriasis causes worldwide concern because of its high-prevalence, as
      well as its harmful, and incurable characteristics. Topical therapy is a
      conventional treatment for psoriasis vulgaris. Chinese medicine (CM) has been
      commonly used in an integrative way for psoriasis patients for many years. Some
      CM therapies have shown therapeutic effects for psoriasis vulgaris (PV),
      including relieving symptoms and improving quality of life, and may reduce the
      relapse rate. However, explicit evidence has not yet been obtained. The purpose
      of the present trial is to examine the efficacy and safety of the YXBCM01
      granule, a compound Chinese herbal medicine, with a combination of topical
      therapy for PV patients. METHODS/DESIGN: Using an add-on design, the trial is to
      evaluate whether the YXBCM01 granule combined topical therapy is more effective
      than topical therapy alone for the treatment of PV. The study design is a double
      blind, parallel, randomized controlled trial comparing the YXBCM01 granule (5.5 g
      twice daily) to a placebo. The duration of treatment is 12 weeks. A total of 600
      participants will be randomly allocated into two groups, YXBCM01 granule group
      and placebo group, from 11 general or dermatological hospitals in China. Topical
      use of calcipotriol betamethasone for the first 4 weeks and calcipotriol ointment
      for the remaining 8 weeks will be the same standard therapy for the two groups.
      Patients will be enrolled if they have a clinical diagnosis of PV, a psoriasis
      area severe index (PASI) of more than 10 or body surface area (BSA) of more than
      10%, but PASI of less than 30 and BSA of less than 30%, are aged between 18 and
      65-years-old, and provide signed informed consent. The primary outcome, relapse
      rate, is based on PASI assessed blindly during the treatment. Secondary outcomes
      include: (i) relapse time interval, (ii) time to onset, (iii) rebound rate, (iv)
      PASI score, (v) cumulative consumption of medicine, (vi) the dermatology quality
      life index (DLQI), and (vii) the medical outcomes study (MOS) item short form
      health survey (SF-36). Analysis will be on intention-to-treat and per-protocol
      subject analysis principles. DISCUSSION: To address the effectual remission of
      the YXBCM01 granule for PV, this trial may provide a novel regimen for PV
      patients if the granule can decrease relapse rate without more adverse effects.
      TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://cwww.chictr.org):
      ChiCTR-TRC-13003233, registered 26 May 2013.

PMID- 25052162
TI  - Smelling directions: olfaction modulates ambiguous visual motion perception.
AB  - Senses of smells are often accompanied by simultaneous visual sensations.
      Previous studies have documented enhanced olfactory performance with concurrent
      presence of congruent color- or shape- related visual cues, and facilitated
      visual object perception when congruent smells are simultaneously present. These
      visual object-olfaction interactions suggest the existences of couplings between
      the olfactory pathway and the visual ventral processing stream. However, it is
      not known if olfaction can modulate visual motion perception, a function that is
      related to the visual dorsal stream. We tested this possibility by examining the
      influence of olfactory cues on the perceptions of ambiguous visual motion
      signals. We showed that, after introducing an association between motion
      directions and olfactory cues, olfaction could indeed bias ambiguous visual
      motion perceptions. Our result that olfaction modulates visual motion processing
      adds to the current knowledge of cross-modal interactions and implies a possible
      functional linkage between the olfactory system and the visual dorsal pathway. 

PMID- 25052163
TI  - Vitamin D protects against diet-induced obesity by enhancing fatty acid
      oxidation.
AB  - Prospective studies reported an inverse correlation between 25-hydroxyvitamin D
      [25(OH)D] plasma levels and prevalence of obesity and type 2 diabetes. In
      addition, 25(OH)D status may be a determinant of obesity onset. However, the
      causality between these observations is not yet established. We studied the
      preventive effect of vitamin D3 (VD3) supplementation (15,000 IU/kg of food for
      10 weeks) on onset of obesity in a diet-induced obesity mouse model. We showed
      that the VD3 supplementation limited weight gain induced by high-fat diet, which
      paralleled with an improvement of glucose homeostasis. The limitation of weight
      gain could further be explained by an increased lipid oxidation, possibly due to
      an up-regulation of genes involved in fatty acid oxidation and mitochondrial
      metabolism, leading to increased energy expenditure. Altogether, these data show
      that VD3 regulates energy expenditure and suggest that VD3 supplementation may
      represent a strategy of preventive nutrition to fight the onset of obesity and
      associated metabolic disorders.

PMID- 25052164
TI  - Changing interpretations of death by neurologic criteria: the McMath case.

PMID- 25052165
TI  - Platelet indices in assessment of in hospital mortality in intensive care unit
      patients.

PMID- 25052166
TI  - g-C3N4 quantum dots: direct synthesis, upconversion properties and photocatalytic
      application.
AB  - Graphitic carbon nitride (g-C3N4) quantum dots (CNQDs) were prepared from bulk g
      C3N4 directly by a thermal-chemical etching process. The CNQDs show strong blue
      emission as well as upconversion behavior, which can be used as universal energy
      transfer components in visible-light-driven metal-free photocatalytic systems. 

PMID- 25052167
TI  - The disrupted basal ganglia and behavioural control: an integrative cross-domain
      perspective of spontaneous stereotypy.
AB  - Spontaneous stereotypic behaviour (SB) is common in many captive animal species,
      as well as in humans with some severe psychiatric disorders, and is often cited
      as being related to general basal ganglia dysfunction. Despite this assertion,
      there is little in the literature examining SB specifically in terms of the basal
      ganglia mechanics. In this review, we attempt to fill this gap by offering an
      integrative, cross-domain perspective of SB by linking what we currently
      understand about the SB phenotype with the ever-growing literature on the anatomy
      and functionality of the basal ganglia. After outlining current models of SB from
      different theoretical perspectives, we offer a broad but detailed overview of
      normally functioning basal ganglia mechanics, and attempt to link this with
      current neurophysiological evidence related to spontaneous SB. Based on this we
      present an empirically derived theoretical framework, which proposes that SB is
      the result of a dysfunctional action selection system that may reflect
      dysregulation of excitatory (direct) and inhibitory (indirect and hyperdirect)
      pathways as well as alterations in mechanisms of behavioural switching. This
      approach also suggests behaviours that specifically become stereotypic may
      reflect inbuilt low selection threshold behavioural sequences associated with
      early development and the species-specific ethogram or, low threshold behavioural
      sequences that are the result of stress-induced dopamine exposure at the time of
      performance. 

PMID- 25052168
TI  - Effectiveness and implementation of enhanced recovery after surgery programmes: a
      rapid evidence synthesis.
AB  - OBJECTIVES: To assess the evidence on the impact of enhanced recovery programmes
      for patients undergoing elective surgery in acute hospital settings in the UK.
      DESIGN: Rapid evidence synthesis. Eight databases were searched from 1990 to
      March 2013 without language restrictions. Relevant reports and guidelines,
      websites and reference lists of retrieved articles were scanned to identify
      additional studies. Systematic reviews, RCTs not included in the systematic
      reviews, economic evaluations and UK NHS cost analysis, implementation case
      studies and surveys of patient experience in a UK setting were eligible for
      inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed the impact of
      enhanced recovery programmes on health or cost-related outcomes, and assessed
      implementation case studies and patient experience in UK settings. Studies were
      quality assessed where appropriate using the Centre for Reviews and Dissemination
      Database of Abstracts of Reviews of Effects critical appraisal process. RESULTS:
      17 systematic reviews and 12 additional RCTs were included. Ten relevant economic
      evaluations were included. No cost analysis studies were identified. Most of the
      evidence focused on colorectal surgery. 14 innovation case studies and 15
      implementation case studies undertaken in National Health Service settings
      described factors critical to the success of an enhanced recovery programme.
      Evidence for colorectal surgery suggests that enhanced recovery programmes may
      reduce hospital stays by 0.5-3.5 days compared with conventional care. There were
      no significant differences in reported readmission rates. Other surgical
      specialties showed greater variation in reductions in length of stay reflecting
      the limited evidence identified. Findings relating to other outcomes were
      hampered by a lack of robust evidence and poor reporting. CONCLUSIONS: There is
      consistent, albeit limited, evidence that enhanced recovery programmes can reduce
      length of patient hospital stay without increasing readmission rates. The extent
      to which managers and clinicians considering implementing enhanced recovery
      programmes in UK settings can realise savings will depend on length of stay
      achieved under their existing care pathway.

PMID- 25052169
TI  - Parental separation and behaviours that influence the health of infants aged 7-11
      months: a cross-sectional study.
AB  - OBJECTIVE: Analyse the parental behaviours that are recognised as influencing the
      health of very young children based on family structure (parents separated or
      not). DESIGN: Cross-sectional study. SETTING: Free preventive medicine
      consultations in the French Community of Belgium. PARTICIPANTS: Examination of 79
      701 infants aged 7-11 months as part of a free preventive medicine consultation.
      The data came from an assessment conducted 7-11 months after birth during which
      information was collected, namely about the parents' use of tobacco, the infant's
      type of nutrition and adherence to vaccination schedules. MAIN OUTCOME MEASURES:
      Parental behaviours: smoking, nutrition and compliance with vaccination schedule.
      RESULTS: The percentage of infants whose parents were separated was 6.6%. After
      adjusting for the cultural and socioeconomic environment as well as for other
      potential confounders, in the event of separation as compared with non-separated
      parents, the adjusted ORs (95% CI) were as follows: 1.5 (1.3 to 1.7) for the
      infant's exposure to tobacco; 1.3 (1.2 to 1.4) for total lack of exclusive breast
      feeding; 1.3 (1.1 to 1.4) and 1.2 (1.1 to 1.2) for breast feeding for a duration
      of less than 3 and 6 months, respectively; 1.2 (1.1 to 1.4) for non-compliance
      with the vaccination schedule against rotavirus. The duration of exclusive breast
      feeding was shorter when parents were separated (p<0.001; median 10 vs 13 weeks).
      CONCLUSIONS: This study reinforces the possibility that parental separation is
      independently associated with certain parental at-risk behaviours regarding the
      children's health. This observation should be verified because this could result
      in major consequences for the work of family doctors, in particular in terms of
      parent information and targeted prevention.

PMID- 25052170
TI  - From hospice to hospital: short-term follow-up study of hospice patient outcomes
      in a US acute care hospital surveillance system.
AB  - OBJECTIVES: In the USA, there is little systematic evidence about the real-world
      trajectories of patient medical care after hospice enrolment. The objective of
      this study was to analyse predictors of the length of stay for hospice patients
      who were admitted to hospital in a retrospective analysis of the mandatorily
      reported hospital discharge data. SETTING: All acute-care hospitals in Florida
      during 1 January 2010 to 30 June 2012. PARTICIPANTS: All patients with source of
      admission coded as 'hospice' (n=2674). PRIMARY OUTCOME MEASURES: The length of
      stay and discharge status: (1) died in hospital; (2) discharged back to hospice;
      (3) discharged to another healthcare facility; and (4) discharged home. RESULTS:
      Patients were elderly (median age=81) with a high burden of disease. Almost half
      died (46%), while the majority of survivors were discharged to hospice (80% of
      survivors, 44% of total). A minority went to a healthcare facility (5.6%) or to
      home (5.2%). Only 9.2% received any procedure. Respiratory services were received
      by 29.4% and 16.8% were admitted to the intensive care unit. The median length of
      stay was 1 day for those who died. In an adjusted survival model, discharge to a
      healthcare facility resulted in a 74% longer hospital stay compared with
      discharge to hospice (event time ratio (ETR)=1.74, 95% CI 1.54 to 1.97 p<0.0001),
      with 61% longer hospital stays among patients discharged home (ETR=1.61, 95% CI
      1.39 to 1.86 p<0.0001). Total financial charges for all patients exceeded $25
      million; 10% of patients who appeared to exit hospice incurred 32% of the
      charges. CONCLUSIONS: Our results raise significant questions about the ethics
      and pragmatics of end-of-life medical care, and the intentions and scope of
      hospices in the USA. Future studies should incorporate prospective linkage of
      subjective patient-centred data and objective healthcare encounter data.

PMID- 25052171
TI  - Preschoolers' parent-rated health disparities are strongly associated with
      measures of adiposity in the Lifeways cohort study children.
AB  - OBJECTIVE: To examine the relationship between lifecourse factors from
      preschoolers' microecosystem and their parent-reported (mother-reported) health
      (PRH), following them prospectively from preconception to age 5 years. To
      investigate if preschoolers' body mass index (BMI) and waist circumference were
      associated with preschoolers' PRH when controlled for lifecourse predictors.
      DESIGN: Lifeways cross-generation cohort study. SETTING: Ireland. PARTICIPANTS:
      Of 1082 families, 62% mothers responded on a health and lifestyle questionnaire
      at follow-up. Food frequency, BMI and waist circumference were measured. There
      were 547 family data sets available for analysis of children's PRH. MAIN OUTCOME
      MEASURE: Mother-reported children's PRH at age 5. Associations with child's
      individual and familial exposures from preconception to age 5 years examined
      using logistic regression. RESULTS: In univariate analysis, relatively positive
      rating of children's PRH were associated with children's lower intake of fats (OR
      (95% CI) 2.2 (1.1 to 4.3)), higher intake of fruits/vegetables (OR (95% CI) 2.2
      (1.1 to 4.3)); as well as familial socioeconomic characteristics {higher
      household income (OR (95% CI) 3.0 (1.6 to 5.9)), non-entitlement to means-tested
      healthcare (OR (95% CI) 2.1 (1.0 to 4.3)), mothers' higher education (OR (95% CI)
      1.9 (1.0 to 3.6))}, psychosocial characteristics {father's participation in study
      (OR (95% CI) 2.1 (1.0 to 4.3)), mothers' perceiving better support from partner
      (OR (95% CI) 2.3 (1.2 to 4.3)), children (OR (95% CI) 1.9 (1.0 to 3.7)) or
      relatives (OR (95% CI) 2.2 (1.1 to 4.1))}, parents' lifestyle {mothers' lower
      intake of energy (OR (95% CI) 2.2 (1.1 to 4.3)), fathers' non-smoking status (OR
      (95% CI) 2.2 (1.1 to 4.4))} and parents' health {mothers' self-rated health
      relatively positive (OR (95% CI) 5.1 (2.6 to 9.9)), fathers' self-rated health
      relatively positive (OR (95% CI) 3.0 (1.5 to 6.0))}. In multivariable analysis
      (chi(2)=34.2, df=21, N=303, R(2 )= 0.26, p<0.05), one of the two strong
      predictors of children's relatively positive PRH was child not being obese by
      International Obesity Task Force classification (OR (95% CI) 5.5 (1.4 to 21.0)),
      observed also using BMI (kg/m(2); OR (95% CI) 0.73 (0.58 to 0.93)) or waist
      circumference (cm; OR (95% CI) 0.89 (0.81 to 0.98)) as continuous variables. The
      other significant predictor was mothers' self-rated health relatively positive
      (OR (95% CI) 4.2 (1.5 to 12.2)). CONCLUSIONS: Preschoolers' health is adversely
      associated with obesity and this is independent of lifecourse and social and
      environmental inequalities. The findings suggest that reducing childhood obesity
      and improving maternal health may be useful ways to improve child's global
      health.

PMID- 25052172
TI  - Visceral leishmaniasis-associated mortality in Bangladesh: a retrospective cross
      sectional study.
AB  - OBJECTIVE: To investigate visceral leishmaniasis (VL) deaths and risk factors in
      two VL endemic areas of Bangladesh. DESIGN: Retrospective cross-sectional.
      SETTING: Two geographically and culturally different VL endemic subdistricts,
      Godagari in the district of Rajshahi and Trishal in the district of Mymensingh in
      Bangladesh, August 2009-December 2011. PARTICIPANTS: 51 094 inhabitants from
      randomly selected Unions in the two subdistricts. MAIN OUTCOME MEASURES: VL
      deaths, confirmed independently by qualified physicians using the verbal autopsy
      procedure ICD10 guideline. RESULTS: The total number of people screened for VL
      deaths was 51 094 from 12 032 households from Godagari and Trishal subdistricts .
      About 16% of the people from Godagari were Tribals. The average age of the study
      population was 25.6 years (SD 18.4) and 49.7% were females. The VL case fatality
      rate averaged 6.12% (12/196) including 2/137 in Trishal and 10/59 in Godagari.
      Most of the VL deaths (9/12, 75%) occurred at home and the rest in tertiary
      hospitals. None of these deaths had been reported in the national VL surveillance
      system. The VL case fatality rate in the Tribal ethnic (22.2%) population was
      about 17 times higher than that in the Bangali ethnic (1.3%) population
      (p<0.0001). Tribal ethnicity had an 18 times (OR=18.1, 95% CI 3.6 to 90.6) higher
      risk for VL deaths compared with Bangali ethnicity (p<0.0001). CONCLUSION: VL
      deaths were found to be high in the study areas and were under-reported. The
      Tribal ethnic population was at the highest risk for VL deaths. The national VL
      Elimination Programme should give special attention to the tribal community in
      the endemic areas, especially for those in Rajshahi, and should strengthen VL
      surveillance by including tertiary hospitals in the national surveillance system.

PMID- 25052173
TI  - Prescription opioid injection and risk of hepatitis C in relation to traditional
      drugs of misuse in a prospective cohort of street youth.
AB  - OBJECTIVE: Despite dramatic increases in the misuse of prescription opioids, the
      extent to which their intravenous injection places drug users at risk of
      acquiring hepatitis C virus (HCV) remains unclear. We sought to compare risk of
      HCV acquisition from injection of prescription opioids to that from other street
      drugs among high-risk street youth. DESIGN: Prospective cohort study. SETTING:
      Vancouver, British Columbia, Canada from September 2005 to November 2011.
      PARTICIPANTS: The At-Risk Youth Study (ARYS) is a prospective cohort of drug
      using adolescents and young adults aged 14-26 years. Participants were recruited
      through street-based outreach and snowball sampling. PRIMARY OUTCOME MEASURE: HCV
      antibody seroconversion, measured every 6 months during follow-up. Risk for
      seroconversion from injection of prescription opioids was compared with injection
      of other street drugs of misuse, including heroin, cocaine or crystal
      methamphetamine, using Cox proportional hazards regression controlling for age,
      gender and syringe sharing. RESULTS: Baseline HCV seropositivity was 10.6%. Among
      512 HCV-seronegative youth contributing 860.2 person-years of follow-up, 56
      (10.9%) seroconverted, resulting in an incidence density of 6.5/100 person-years.
      In bivariate analyses, prescription opioid injection (HR=3.48; 95% CI 1.57 to
      7.70) predicted HCV seroconversion. However, in multivariate modelling, only
      injection of heroin (adjusted HR=4.56; 95% CI 2.39 to 8.70), cocaine (adjusted
      HR=1.88; 95% CI 1.00 to 3.54) and crystal methamphetamine (adjusted HR=2.91; 95%
      CI 1.57 to 5.38) remained independently associated with HCV seroconversion,
      whereas injection of prescription opioids did not (adjusted HR=0.94; 95% CI 0.40
      to 2.21). CONCLUSIONS: Although misuse of prescription opioids is on the rise,
      traditional street drugs still posed the greatest threat of HCV transmission in
      this setting. Nonetheless, the high prevalence and incidence of HCV among
      Canadian street youth underscore the need for evidence-based drug prevention,
      treatment and harm reduction interventions targeting this vulnerable population.

PMID- 25052174
TI  - 'This isn't what mine looked like': a qualitative study of symptom appraisal and
      help seeking in people recently diagnosed with melanoma.
AB  - OBJECTIVE: To explore symptom appraisal and help-seeking decisions among patients
      recently diagnosed with melanomas, and to compare experiences of people with
      'thinner' (<1 mm) and 'thicker' (>2 mm) melanomas, as thickness at diagnosis is
      an important prognostic feature. METHODS: In-depth interviews with patients
      within 10 weeks of melanoma diagnosis explored the factors impacting on their
      pathways to diagnosis. Framework analysis, underpinned by the Model of Pathways
      to Treatment, was used to explore the data with particular focus on patients'
      beliefs and experiences, disease factors, and healthcare professional (HCP)
      influences. RESULTS: 63 patients were interviewed (29-93 years, 31 women, 30
      thicker melanomas). All described their skin changes using rich lay vocabulary.
      Many included unassuming features such as 'just a little spot' as well as common
      features of changes in size, colour and shape. There appeared to be subtly
      different patterns of symptoms: descriptions of vertical growth, bleeding, oozing
      and itch were features of thicker melanomas irrespective of pathological type.
      Appraisal was influenced by explanations such as normal life changes, prior
      beliefs and whether skin changes matched known melanoma descriptions. Most
      decisions to seek help were triggered by common factors such as advice from
      family and friends. 11 patients reported previous reassurance about their skin
      changes by a HCP, with little guidance on monitoring change or when it would be
      appropriate to re-consult. CONCLUSIONS: Patients diagnosed with both thinner and
      thicker melanomas often did not initially recognise or interpret their skin
      changes as warning signs or prompts to seek timely medical attention. The
      findings provide guidance for melanoma awareness campaigns on more appropriate
      images, helpful descriptive language and the need to stress the often apparently
      innocuous nature of potentially serious skin changes. The importance of
      appropriate advice, monitoring and safety-netting procedures by HCPs for people
      presenting with skin changes is also highlighted.

PMID- 25052175
TI  - Functionality and feedback: a protocol for a realist synthesis of the collation,
      interpretation and utilisation of PROMs data to improve patient care.
AB  - INTRODUCTION: The feedback and public reporting of PROMs data aims to improve the
      quality of care provided to patients. Existing systematic reviews have found it
      difficult to draw overall conclusions about the effectiveness of PROMs feedback.
      We aim to execute a realist synthesis of the evidence to understand by what means
      and in what circumstances the feedback of PROMs data leads to the intended
      service improvements. METHODS AND ANALYSIS: Realist synthesis involves (stage 1)
      identifying the ideas, assumptions or 'programme theories' which explain how
      PROMs feedback is supposed to work and in what circumstances and then (stage 2)
      reviewing the evidence to determine the extent to which these expectations are
      met in practice. For stage 1, six provisional 'functions' of PROMs feedback have
      been identified to structure our review (screening, monitoring, patient
      involvement, demand management, quality improvement and patient choice). For each
      function, we will identify the different programme theories that underlie these
      different goals and develop a logical map of the respective implementation
      processes. In stage 2, we will identify studies that will provide empirical tests
      of each component of the programme theories to evaluate the circumstances in
      which the potential obstacles can be overcome and whether and how the unintended
      consequences of PROMs feedback arise. We will synthesise this evidence to (1)
      identify the implementation processes which support or constrain the successful
      collation, interpretation and utilisation of PROMs data; (2) identify the
      implementation processes through which the unintended consequences of PROMs data
      arise and those where they can be avoided. ETHICS AND DISSEMINATION: The study
      will not require NHS ethics approval. We have secured ethical approval for the
      study from the University of Leeds (LTSSP-019). We will disseminate the findings
      of the review through a briefing paper and dissemination event for National
      Health Service stakeholders, conferences and peer reviewed publications.

PMID- 25052176
TI  - Injury of the mammillothalamic tract in patients with subarachnoid haemorrhage: a
      retrospective diffusion tensor imaging study.
AB  - OBJECTIVE: Few studies have reported on injury of the mammillothalamic tract
      (MTT) in patients with stroke. However, no study in patients with subarachnoid
      haemorrhage (SAH) has been reported. Using diffusion tensor tractography, we
      attempted to investigate injury of the MTT in patients with SAH. METHODS: We
      recruited 16 patients with SAH and 15 control participants. DTI was obtained at
      5.7+/-1.5 weeks after onset and reconstruction of the MTT was performed using the
      probabilistic tractography method. The fractional anisotropy (FA) value and tract
      number of the MTT and the Mini-Mental State Examination (MMSE) score were
      determined. Values of FA and tract volume showing a decrement of more than two
      SDs that of normal control were defined as abnormal. RESULTS: The FA value and
      tract volume in the patient group were significantly lower than those in the
      control group (p<0.05). In addition, MMSE showed strong (r=0.67, p=0.005)
      positive correlation with tract volume without correlation with FA. In the
      individual analysis, 16 MTTs of 32 MTTs in 16 patients showed abnormalities of
      the MTT in terms of the FA value, the tract volume or the presence of a
      reconstructed MTT. As a result, 10 (62.5%) of 16 patients showed abnormality of
      the MTT in at least one hemisphere. CONCLUSIONS: We found that patients with SAH
      showed injury of the MTT and this injury showed correlation with cognitive
      dysfunction.

PMID- 25052177
TI  - Tea consumption and risk of type 2 diabetes mellitus: a systematic review and
      meta-analysis update.
AB  - OBJECTIVE: Tea has been suggested to decrease blood glucose levels and protect
      pancreatic beta cells in diabetic mice. However, human epidemiological studies
      showed inconsistent results for the association between tea consumption and type
      2 diabetes mellitus (T2DM) risk. The aim of this study was to conduct a meta
      analysis to further explore the association between tea consumption and incidence
      of T2DM. DESIGN: Systematic review and meta-analysis. METHODS: We performed a
      systematic literature search up to 30 August 2013 in PubMed, EMBASE, Chinese
      Wanfang Database and CNKI database. Pooling relative risks (RRs) were estimated
      by random-effect models. Two kinds of subgroup analyses (according to sex and
      regions) were performed. Sensitive analyses were performed according to types of
      tea. RESULTS: Overall, no statistically significant relationship between tea
      consumption and risk of T2DM was found based on 12 eligible studies (pooling RR
      0.99, 95% CI 0.95 to 1.03). Compared with the lowest/non-tea group, daily tea
      consumption (>=3 cups/day) was associated with a lower T2DM risk (RR 0.84, 95% CI
      0.73 to 0.97). Subgroup analyses showed a difference between men and women.
      Overall, the RRs (95% CI) were 0.92 (0.84 to 1.00) for men, and 1.00 (0.96 to
      1.05) for women, respectively. Tea consumption of >=3 cups/day was associated
      with decreased T2DM risk in women (RR 0.84, 95% CI 0.71 to 1.00). Overall, the
      RRs (95% CIs) were 0.84 (0.71 to 1.00) for Asians, and 1.00 (0.97 to 1.04) for
      Americans and Europeans, respectively. No obvious change was found in sensitivity
      analyses. CONCLUSIONS: The results suggest that daily tea consumption (>=3
      cups/day) is associated with a lower T2DM risk. However, further studies are
      needed to enrich related evidence, especially with regard to types of tea or sex.

PMID- 25052179
TI  - Formation of ultra-long nanoribbons by self-assembly of carbon dots and anionic
      oligomers for multi-colored fluorescence and electrical conduction.
AB  - We report a facile and scalable synthesis of ultra-long (>100 MUm) nanoribbons
      based on self-assembly of positively charged carbon dots (C-dots) and anionic
      oligomers of styrene and 4-styrenesulfonate (PS-PSS) in a mixture of ethanol and
      water (4/1, v/v). The obtained hybrid (PS-PSS)/C-dot nanoribbons show a multi
      colored fluorescence and an electrical conductivity of 3.368 S m(-1). 

PMID- 25052178
TI  - Internet-based vestibular rehabilitation for adults aged 50 years and over: a
      protocol for a randomised controlled trial.
AB  - INTRODUCTION: Dizziness is highly prevalent in older adults and can lead to
      falls, fear of falling, loss of confidence, anxiety and depression. Vestibular
      rehabilitation (VR) exercises are effective in reducing dizziness due to
      vestibular dysfunction, but access to trained therapists is limited. Providing
      dizzy patients with booklets teaching them how to carry out VR exercises has been
      shown to be a cost-effective way of managing dizziness in primary care. Internet
      based intervention delivery has many advantages over paper-based methods,
      including the provision of video instructions, automated tailoring and symptom
      related feedback. This trial will examine whether an internet-based VR
      intervention is (1) effective in reducing dizziness and (2) a cost-effective
      primary care treatment option. METHODS/ANALYSIS: This will be a single blind,
      randomised controlled trial carried out in UK primary care. A stand-alone
      internet-based VR intervention will be compared with routine care in 262 dizzy
      patients aged 50 years and over. Measures will be taken at baseline, 3 and 6
      months. Our primary outcome measure will be the effectiveness of the intervention
      in reducing dizziness symptoms compared with routine care at 6 months. Cost
      effectiveness will be examined along with the effect of the intervention on
      dizziness-related disability and symptoms of depression and anxiety.
      Psychological process variables including expectancy, self-efficacy and
      acceptance will be explored in relation to adherence and symptom reduction.
      ETHICS/DISSEMINATION: This trial has undergone ethical scrutiny and been approved
      by an NHS Research Ethics Committee, Southampton A REC Reference: 13/SC/0119. The
      findings of this trial will be disseminated to the scientific community through
      presentations at national and international conferences, and by publishing in
      peer review journals. Findings will be disseminated to the public through
      targeted press releases. This trial will provide valuable information on the role
      of internet interventions in facilitating self-management in older adults. TRIAL
      REGISTRATION NUMBER ISRCTN: 86912968.

PMID- 25052180
TI  - The complete mitochondrial genome of the scab mite Psoroptes cuniculi
      (Arthropoda: Arachnida) provides insights into Acari phylogeny.
AB  - BACKGROUND: Limited available sequence information has greatly impeded population
      genetics, phylogenetics and systematics studies in the subclass Acari (mites and
      ticks). Mitochondrial (mt) DNA is well known to provide genetic markers for
      investigations in these areas, but complete mt genomic data have been lacking for
      many Acari species. Herein, we present the complete mt genome of the scab mite
      Psoroptes cuniculi. METHODS: P. cuniculi was collected from a naturally infected
      New Zealand white rabbit from China and identified by morphological criteria. The
      complete mt genome of P. cuniculi was amplified by PCR and then sequenced. The
      relationships of this scab mite with selected members of the Acari were assessed
      by phylogenetic analysis of concatenated amino acid sequence datasets by Bayesian
      inference (BI), maximum likelihood (ML) and maximum parsimony (MP). RESULTS: This
      mt genome (14,247 bp) is circular and consists of 37 genes, including 13 genes
      for proteins, 22 genes for tRNA, 2 genes for rRNA. The gene arrangement in mt
      genome of P. cuniculi is the same as those of Dermatophagoides farinae
      (Pyroglyphidae) and Aleuroglyphus ovatus (Acaridae), but distinct from those of
      Steganacarus magnus (Steganacaridae) and Panonychus citri (Tetranychidae).
      Phylogenetic analyses using concatenated amino acid sequences of 12 protein
      coding genes, with three different computational algorithms (BI, ML and MP),
      showed the division of subclass Acari into two superorders, supported the
      monophylies of the both superorders Parasitiformes and Acariformes; and the three
      orders Ixodida and Mesostigmata and Astigmata, but rejected the monophyly of the
      order Prostigmata. CONCLUSIONS: The mt genome of P. cuniculi represents the first
      mt genome of any member of the family Psoroptidae. Analysis of mt genome
      sequences in the present study has provided new insights into the phylogenetic
      relationships among several major lineages of Acari species.

PMID- 25052181
TI  - Health-related quality of life and its predictors among outpatients with coronary
      heart disease in Singapore.
AB  - AIMS AND BACKGROUND: Coronary heart disease (CHD) is a major cause of death and
      disability and negatively impacts on patients' health-related quality of life
      (HRQoL). This study aimed to explore HRQoL and identify its predictors among
      outpatients with CHD in Singapore. METHODS: A correlational study was conducted
      with a convenience sample of 106 outpatients with CHD recruited from a public
      hospital. HRQoL outcomes were measured using the Short Form-12 Health Survey (SF
      12), Medical Outcomes Study Social Support Survey (MOS-SSS) and Hospital Anxiety
      and Depression Scale (HADS). RESULTS: Patients reported a generally high level of
      HRQoL as assessed by SF-12. Those aged over 65years reported significantly higher
      mental health and those who were married had higher levels of education or income
      reported significantly higher physical health. There were significant negative
      correlations between physical and mental health and anxiety and depression
      (p<.05). Perceived social support was negatively correlated with anxiety and
      depression and positively correlated with mental health. Education level and
      depression significantly predicted physical health, while age, anxiety and
      depression predicted mental health. CONCLUSION: Anxiety, depression, age and
      education are significant predictors of HRQoL in this patient population and
      should be assessed routinely and, where appropriate, addressed through
      individually-tailored interventions.

PMID- 25052182
TI  - Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth
      replacement.
AB  - Oral and general health is compromised by irreversible dental problems, including
      dental caries, periodontal disease and tooth injury. Regenerative therapy for
      tooth tissue repair and whole-tooth replacement is currently considered a novel
      therapeutic concept with the potential for the full recovery of tooth function.
      Several types of stem cells and cell-activating cytokines have been identified in
      oral tissues. These cells are thought to be candidate cell sources for tooth
      tissue regenerative therapies because they have the ability to differentiate into
      tooth tissues in vitro and in vivo. Whole-tooth replacement therapy is regarded
      as an important model for the development of an organ regenerative concept. A
      novel three-dimensional cell-manipulation method, designated the organ germ
      method, has been developed to recapitulate organogenesis. This method involves
      compartmentalisation of epithelial and mesenchymal cells at a high cell density
      to mimic multicellular assembly conditions and epithelial-mesenchymal
      interactions. A bioengineered tooth germ can generate a structurally correct
      tooth in vitro and erupt successfully with the correct tooth structure when
      transplanted into the oral cavity. We have ectopically generated a bioengineered
      tooth unit composed of a mature tooth, periodontal ligament and alveolar bone,
      and that tooth unit was successfully engrafted into an adult jawbone through bone
      integration. Such bioengineered teeth were able to perform normal physiological
      tooth functions, such as developing a masticatory potential in response to
      mechanical stress and a perceptive potential for noxious stimuli. In this review,
      we describe recent findings and technologies underpinning tooth regenerative
      therapy. 

PMID- 25052183
TI  - Clinical and histological resolution of a basal cell carcinoma in a patient
      undergoing concurrent treatment of B-cell lymphoma with systemic R-CHOP.
AB  - Surgical resection is the definitive treatment modality for basal cell carcinoma
      (BCC). However, not all patients may be suitable for surgery. We describe a
      patient with a BCC, which resolved clinically and histologically when he
      underwent systemic R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine
      and prednisolone) for treatment of a high grade B-cell lymphoma. Although topical
      and intra-lesional 5-fluorouracil (5-FU) has been used as an adjunct to
      treatment, more recent reports have illustrated the treatment of BCC with
      systemic 5-FU in combination with bleomycin and cisplatin. We postulate that the
      combination of cyclophosphamide and doxorubicin with rituximab and prednisolone,
      which has not been previously reported in the literature, contributed to
      remission in this case.

PMID- 25052184
TI  - Using a microbial physiologic and genetic approach to investigate how bacteria
      sense physical stimuli.
AB  - A laboratory exercise was designed to illustrate how physical stimuli such as
      temperature and light are sensed and processed by bacteria to elaborate adaptive
      responses. In particular, we use the well-characterized Des pathway of Bacillus
      subtilis to show that temperature modulates gene expression, resulting ultimately
      in modification of the levels of unsaturated fatty acids required to maintain
      proper membrane fluidity at different temperatures. In addition, we adapt recent
      findings concerning the modulation by light of traits related to virulence such
      as motility and biofilm formation in the chemotropic bacterium Acinetobacter
      baumannii. Beyond the theoretical background that this activity provides
      regarding sensing of environmental stimuli, the experimental setup includes
      approaches derived from classic genetics, microbiology, and biochemistry. The
      incorporation of these kind of teaching and training activities in middle
      advanced Microbiology or Bacterial Genetics courses promotes acquisition of
      general and specific techniques and improves student's comprehension of
      scientific literature and research.

PMID- 25052185
TI  - Pattern of genetic variation of yellow catfish Pelteobagrus fulvidraco Richardso
      in Huaihe river and the Yangtze river revealed using mitochondrial DNA control
      region sequences.
AB  - Genetic variability and population genetic structure of the yellow catfish
      Pelteobagrus fulvidraco Richardso in the Huaihe river and the Yangtze river was
      examined with a 810-bp of the mitochondrial DNA control region. A total of 70
      haplotypes were identified from 145 samples, which were characterized with high
      haplotype diversity (h = 0.9832 +/- 0.0041) but low nucleotide diversity (pi =
      0.0415 +/- 0.0201). The analysis of molecular variance and phylogenetic
      reconstructions detected significant geographic structure between Huaihe river
      and Yangtze with FST = 0.1183 (P = 0.0000). Neighbor-joining (NJ) phylogenetic
      analyses identified two distinct clades (bootstrap support 99 %). The medium
      joining network drawn using the complete data set was reticulated and also
      distinctly split the 70 haplotypes into two groups corresponding to those of the
      NJ tree. Departures from neutrality were not significant for the Huaihe river and
      the Yangtze river Pelteobagrus fulvidraco, concordant with the observed
      multimodal mismatch distributions (P > 0.05), which suggested that the effective
      size of this species has been large and stable for a long period. The question
      about the existence of significant genetic differentiation for Pelteobagrus
      fulvidraco in the Yangtze river and Huaihe river basins remains to be further
      studied with molecular nuclear markers and larger sample sizes from throughout
      the river basins.

PMID- 25052186
TI  - Combined effects of the BDNF rs6265 (Val66Met) polymorphism and environment risk
      factors on psoriasis vulgaris.
AB  - Smoking, alcohol consumption and higher body mass index (BMI) are well
      established risk factors for psoriasis and also associated with the clinical
      traits of the disease. And the genetic influences on these three risk factors
      indeed exist. Previously studies have demonstrated these risk factors related
      genetic variants may also play a role in the development of risk factors-related
      diseases. Then we performed a hospital-based study in order to evaluate the
      combined effect of the risk factors and their related polymorphism rs6265 in
      brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and
      clinic traits. The case-control study involved 660 subjects including 345 cases
      and 315 controls in Chinese Han population. The variant of rs6265 was typed by
      SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher
      BMI (>=25), smoking and alcohol consumption were risk factors for PV, and the
      estimated ORs were 1.63(95 % confidence interval (CI); 1.12-2.37), 2.09(95 % CI;
      1.44-3.03) and 1.65(95 % CI; 1.15-2.37) respectively. Genotype and allele
      distributions did not differ significantly between case and control. However, we
      found combined effect of rs6265 genotype (GG) and higher BMI (>=25) increased
      risk of PV (OR = 2.09; 95 % CI, 1.02-4.28; P < 0.05; adjusted OR = 3.19; 95 % CI,
      1.37-7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09
      6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10-1.40; P < 0.05). But none such
      significant combined effect was observed between others genotype (AA and AG) and
      other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype
      (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese
      Han population.

PMID- 25052187
TI  - A stress-responsive late embryogenesis abundant protein 7 (CsLEA7) of tea
      [Camellia sinensis (L.) O. Kuntze] encodes for a chaperone that imparts tolerance
      to Escherichia coli against stresses.
AB  - The present study characterized CsLEA7, a group 7 late embryogenesis abundant
      (LEA) gene, from tea [Camellia sinensis (L.) O. Kuntze]. The gene had an open
      reading frame of 462 base pairs encoding 153 amino acids with calculated
      molecular weight of 16.63 kDa and an isoelectric point (pI) of 4.93. Analysis
      revealed CsLEA7 to be an intrinsically ordered protein consisting of nine beta
      strands and two alpha-helices. CsLEA7 expressed ubiquitously in all the tissues
      analyzed with highest level of transcripts in mature leaf as compared to in
      flower bud, younger leaves, stem and fruit. Expression was the least in root
      tissue. CsLEA7 exhibited up-regulation in response to low temperature,
      polyethylene glycol-8000, sodium chloride and hydrogen peroxide in tea. Analysis
      of the promoter of CsLEA7 revealed a core promoter element and distinct cis
      acting regulatory elements regulating gene expression under abiotic stresses.
      CsLEA7 exhibited chaperonic activity as evinced by protection to malate
      dehydrogenase against heat denaturation assay. Recombinant Escherichia coli cells
      producing CsLEA7 exhibited improved tolerance against diverse cues: polyethylene
      glycol-8000, sodium chloride, hydrogen peroxide and low temperature signifying
      its role in imparting stress tolerance. 

PMID- 25052188
TI  - The low expression of Dmrt7 is associated with spermatogenic arrest in cattle
      yak.
AB  - Dmrt7 is a member of the DM domain family of genes. Dmrt7 deficiency is also a
      strong candidate as a cause for male cattle-yak infertility, as it is regarded as
      essential for male spermatogenesis, between the pachynema and diplonema stages.
      In our study, the coding region sequence of yak and cattle-yak Dmrt7 was cloned
      by molecular cloning techniques, and the sequence, conserved domains, functional
      sites, and secondary and tertiary structures of the Dmrt7-encoded protein were
      predicted and analyzed using bioinformatics methods. The coding region sequences
      of the Dmrt7 gene, encoding 370 amino acids, were consistent in yak and cattle
      yak. The protein encoded by yak and cattle-yak Dmrt7 contains a DM domain. We
      detected Dmrt7 mRNA expression in testis, but not in any other tissue. Dmrt7 mRNA
      and protein expression was significantly higher in testis of cattle and yak than
      that in cattle-yak (p < 0.01). Histological analysis indicated that seminiferous
      tubules in male cattle-yak were highly vacuolated and contained primarily Sertoli
      cells and spermatogonia, while those of cattle and yak contained abundant primary
      spermatocytes. Male cattle-yak testis contained a significantly larger number of
      apoptotic cells than those in cattle and yak assessed by terminal
      deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) analysis. The
      accumulation of SCP3-positive spermatocytes indicated the arrest of
      spermatogenesis at the pachynema stage in the cattle-yak. These results suggest
      low levels of Dmrt7 expression lead to male sterility in cattle-yak. The
      molecular function of Dmrt7 and the regulation of its expression warrant need to
      be examined in future studies. 

PMID- 25052189
TI  - Orthodontic care for the behavior-challenged special needs patient.
AB  - Despite having a high prevalence of functionally compromising malocclusions,
      individuals with intellectual and developmental disabilities do not regularly
      receive necessary orthodontic treatment. Patients with behavior challenges are
      unlikely to be offered this treatment option. However, with appropriate behavior
      management interventions and pharmacologic sedation, orthodontic treatment
      becomes a possibility for clinicians to consider. Parents will likely seek out
      clinicians who can provide this type of advanced orthodontic care. Additional
      training is now becoming available as accredited Fellowship Programs in
      Craniofacial and Special Care Orthodontics are developed. Hopefully, the clinical
      examples described in this article will no longer be unique in the area of
      special care dentistry. 

PMID- 25052190
TI  - Inflammatory bowel disease is associated with an increased risk of
      hospitalization for heart failure: a Danish Nationwide Cohort study.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) has been linked to adverse
      cardiovascular events, but a relation to heart failure (HF) is uncertain. We
      investigated the IBD-associated risk of HF in a nationwide setting. METHODS AND
      RESULTS: A total of 5 436 647 Danish citizens, with no history of IBD or HF, were
      included on January 1, 1997, and followed up until first hospitalization for HF,
      death, or December 31, 2011. Of these subjects, 23 681 developed IBD for which
      disease activity was determined continuously throughout the study. The risk of
      hospitalization for HF was estimated with a Poisson regression model adjusting
      for comorbidity and cardiovascular pharmacotherapy as time-dependent covariates.
      During a mean follow-up of 11.8 years in the reference population and 6.4 years
      in the IBD group, hospitalization for HF occurred in 553 subjects with IBD and
      171 405 in the reference population. Patients with IBD had a 37% increased risk
      of hospitalization for HF (incidence rate ratio, 1.37; 95% confidence interval,
      1.26-1.49) compared with the reference population. IBD activity-specific analyses
      showed markedly increased risk of HF hospitalization during flares (incidence
      rate ratio, 2.54; 95% confidence interval, 2.13-3.04) and persistent activity
      (incidence rate ratio, 2.73; 95% confidence interval, 2.25-3.33) but not in IBD
      remission (incidence rate ratio, 1.04; 95% confidence interval, 0.94-1.16).
      CONCLUSIONS: In a nationwide cohort, IBD was associated with an increased risk of
      hospitalization for HF, and this risk was strongly correlated to periods of
      active disease. The mechanisms underlying this finding warrant further studies.

PMID- 25052191
TI  - JC virus urinary excretion and seroprevalence in natalizumab-treated multiple
      sclerosis patients.
AB  - The risk of developing progressive multifocal leukoencephalopathy (PML), as a
      consequence of infection/reactivation with JC virus (JCV), is consistent in
      natalizumab-treated multiple sclerosis (MS) patients, with 430 cases of PML
      reported so far. The risk of PML is higher in JCV seropositive patients, and it
      is recommended that only MS patients without JCV antibodies should be enrolled in
      the treatment postulating that they do not have JCV infection.We have studied
      forty-two natalizumab-treated MS patients, and urine and blood were collected
      monthly for up to 60 months. JCV and BK virus (BKV) DNA presence was verified
      using quantitative real-time PCR assays, and serum anti-JCV antibodies were
      measured with the Stratify and/or Stratify DxSelect tests.JCV and BKV DNA were
      not found in the blood samples, whereas they were found at least once in the
      urine of 21 of 42 (50 %) and of 25/42 (59.5 %) patients, respectively. JCV DNA
      urinary shedding increased up to month 24 of natalizumab treatment (45.2 %), and
      the effect of time was significant for JCV (p = 0.04), but not for BKV (p =
      0.39). JCV viruria and seropositivity did not completely correlate, since three
      patients shedding JCV DNA in the urine were seronegative according to the
      serological tests.The results indicated that natalizumab therapy may increase the
      rate of JCV urinary shedding. Additionally, we confirmed that the identification
      of JCV carriers cannot solely rely on serological tests, but sensitive methods
      for viral DNA detection should be adopted to more precisely identify the truly
      JCV uninfected cases.

PMID- 25052192
TI  - Theiler's virus infection provokes the overexpression of genes coding for the
      chemokine Ip10 (CXCL10) in SJL/J murine astrocytes, which can be inhibited by
      modulators of estrogen receptors.
AB  - Theiler's murine encephalomyelitis virus (TMEV) induces demyelination in
      susceptible strains of mice (SJL/J) through an immunopathological process that is
      mediated by CD4(+) Th1 T cell. These T cells are chemoattracted to the central
      nervous system by chemokines. Hence, in this study, we focused on the production
      of the chemokine "interferon-gamma-inducible protein 10 kDa," or IP-10/CXCL10, by
      cultured SJL/J mouse astrocytes infected with the BeAn strain of TMEV and its
      capacity to attract activated T cells. The analysis of the whole murine genome by
      DNA hybridization with cRNAs from mock- and TMEV-infected cultures revealed the
      upregulation of six sequences that potentially encode for CXCL10. This increased
      CXCL10 expression was validated by PCR and qPCR. The presence of this chemokine
      was further demonstrated by enzyme-linked immunoassay (ELISA). Significantly,
      astrocytes from BALB/c mice, a strain resistant to demyelination, did not produce
      CXCL10. The secreted CXCL10 was biologically active, inducing chemoattraction of
      activated lymphocytes. The inflammatory cytokines, IL-1alpha, IFN-gamma, and TNF
      alpha, were strong inducers of CXCL10 in astrocytes. Serum from TMEV-infected
      SJL/J but not BALB/c mice contains CXCL10, the levels of which peak at the onset
      of the clinical disease. Finally, this in vitro inflammation model was fully
      inhibited by 17beta-estradiol and four selective estrogen receptor modulators, as
      demonstrated by ELISA and qPCR.

PMID- 25052194
TI  - Establishment condition and characterization of heart-derived cell culture in
      Siberian sturgeon (Acipenser baerii).
AB  - This study was conducted to establish the efficient condition for stable
      derivation of heart-derived cell culture in Siberian sturgeon (Acipenser baerii).
      Three factors including isolation methods, cell densities in initial seeding, and
      basal media were evaluated for the derivation of heart-derived cell culture. As
      the results, enzymatic isolation was more efficient than mechanical isolation in
      both cell retrieval and further culture. Total 48 trials of culture employing low
      and middle cell densities of less than 5.5 * 10(4) cells/cm(2) in initial seeding
      did not induce cell survivals (0%, 0/48), but the trials in high cell density of
      more than 5.5 * 10(5) cells/cm(2) could induce cell survival and primary cell
      attachment on the plate (88.9%, 24 in 27 trials). When all initially attached
      cell populations were continuously cultured in two different media, only five
      cell populations that were enzymatically isolated and cultured under Leibovitz's
      L-15 medium could grow up to more than 40th subculture. Each cell population was
      stably cultured according to its own growth rate and all showed normal diploid
      DNA contents. Two morphologically different cell types that has an elongated
      shape or a round shape were identified in culture, which was subsequently
      identified that two cell types are considered as a fibroblast (an elongated
      shape) and a vascular endothelial cell (a round shape) on the basis of the
      results of gene and protein expression analysis. Additionally, the sufficient
      number of viable cells could be successfully retrieved after freezing and thawing
      from all five cell populations suggesting the feasibility of long-term
      cryopreservation of the cells. The data and cells obtained from this study will
      contribute to development of in vitro model for basic biological studies using
      sturgeon species.

PMID- 25052193
TI  - Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse
      model for Down syndrome reveals global disruption of interferon-related molecular
      networks.
AB  - BACKGROUND: The Ts1Cje mouse model of Down syndrome (DS) has partial triplication
      of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome
      21. These mice develop various neuropathological features identified in DS
      individuals. We analysed the effect of partial triplication of the MMU16 segment
      on global gene expression in the cerebral cortex, cerebellum and hippocampus of
      Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84. RESULTS: Gene
      expression profiling identified a total of 317 differentially expressed genes
      (DEGs), selected from various spatiotemporal comparisons, between Ts1Cje and
      disomic mice. A total of 201 DEGs were identified from the cerebellum, 129 from
      the hippocampus and 40 from the cerebral cortex. Of these, only 18 DEGs were
      identified as common to all three brain regions and 15 were located in the
      triplicated segment. We validated 8 selected DEGs from the cerebral cortex
      (Brwd1, Donson, Erdr1, Ifnar1, Itgb8, Itsn1, Mrps6 and Tmem50b), 18 DEGs from the
      cerebellum (Atp5o, Brwd1, Donson, Dopey2, Erdr1, Hmgn1, Ifnar1, Ifnar2, Ifngr2,
      Itgb8, Itsn1, Mrps6, Paxbp1, Son, Stat1, Tbata, Tmem50b and Wrb) and 11 DEGs from
      the hippocampus (Atp5o, Brwd1, Cbr1, Donson, Erdr1, Itgb8, Itsn1, Morc3, Son,
      Tmem50b and Wrb). Functional clustering analysis of the 317 DEGs identified
      interferon-related signal transduction as the most significantly dysregulated
      pathway in Ts1Cje postnatal brain development. RT-qPCR and western blotting
      analysis showed both Ifnar1 and Stat1 were over-expressed in P84 Ts1Cje cerebral
      cortex and cerebellum as compared to wild type littermates. CONCLUSIONS: These
      findings suggest over-expression of interferon receptor may lead to over
      stimulation of Jak-Stat signaling pathway which may contribute to the
      neuropathology in Ts1Cje or DS brain. The role of interferon mediated activation
      or inhibition of signal transduction including Jak-Stat signaling pathway has
      been well characterized in various biological processes and disease models
      including DS but information pertaining to the role of this pathway in the
      development and function of the Ts1Cje or DS brain remains scarce and warrants
      further investigation.

PMID- 25052195
TI  - A pilot external quality assurance study of transfusion screening for HIV, HCV
      and HBsAG in 12 African countries.
AB  - BACKGROUND AND OBJECTIVES: Serologic screening for the major transfusion
      transmissible viruses (TTV) is critical to blood safety and has been widely
      implemented. However, actual performance as measured by proficiency testing has
      not been well studied in sub-Saharan Africa. Therefore, we conducted an external
      quality assessment of laboratories engaged in transfusion screening in the
      region. MATERIALS AND METHODS: Blinded test panels, each comprising 25 serum
      samples that were pedigreed for HIV, HBsAg, HCV and negative status, were sent to
      participating laboratories. The panels were tested using the laboratories'
      routine donor screening methods and conditions. Sensitivity and specificity were
      calculated, and multivariable analysis was used to compare performance against
      mode of testing, country and infrastructure. RESULTS: A total of 12 African
      countries and 44 laboratories participated in the study. The mean (range)
      sensitivities for HIV, HBsAg and HCV were 91.9% (14.3-100), 86.7% (42.9-100) and
      90.1% (50-100), respectively. Mean specificities for HIV, HBsAg and HCV were
      97.7%, 97% and 99.5%, respectively. After adjusting for country and
      infrastructure, rapid tests had significantly lower sensitivity than enzyme
      immunoassays for both HBsAg (P < 0.0001) and HCV (P < 0.05). Sensitivity also
      varied by country and selected infrastructure variables. CONCLUSION: While
      specificity was high, sensitivity was more variable and deficient in a
      substantial number of testing laboratories. These findings underscore the
      importance of proficiency testing and quality control, particularly in Africa
      where TTV prevalence is high.

PMID- 25052196
TI  - Expression of the oestrogen receptor GPER by testicular peritubular cells is
      linked to sexual maturation and male fertility.
AB  - Besides the two nuclear oestrogen receptors (ESR1/ESR2), the G protein-coupled
      oestrogen receptor (GPER) was described in the human testis but little is known
      about testicular GPER during development or male infertility. We performed an
      immunohistochemical analysis using human and rhesus monkey testicular samples.
      The results obtained in adult primate testes showed GPER in interstitial and
      vascular cells as well as in smooth muscle-like peritubular cells, which build
      the wall of seminiferous tubules. Expression of GPER was also found in cultured
      human testicular peritubular cells (HPTCs) by Western blotting and RT
      PCR/sequencing. Furthermore, as seen in time-lapse videos of cultured cells,
      addition of a specific GPER agonist (G1) significantly reduced the numbers of
      HTPCs within 24 h. A GPER antagonist (G15) prevented this action, implying a role
      for GPER related to the control of cell proliferation or cell death of
      peritubular cells. Peritubular cell functions and their phenotype change, for
      example, during post-natal development and in the cases of male infertility. The
      study of non-human primate samples revealed that GPER in peritubular cells was
      detectable only from the time of puberty onwards, while in samples from infantile
      and prepubertal monkeys only interstitial cells showed immunopositive staining.
      In testicular biopsies of men with mixed atrophy, a reduction or loss of
      immunoreactive GPER was found in peritubular cells surrounding those tubules, in
      which spermatogenesis was impaired. In other cases of impaired spermatogenesis,
      namely when the tubular wall was fibrotically remodelled, a complete loss of GPER
      was seen. Thus, the observed inverse relation between the state of fertility and
      GPER expression by peritubular cells implies that the regulation of primate
      testicular peritubular cells by oestrogens is mediated by GPER in both, health
      and disease.

PMID- 25052197
TI  - delta-Opioid receptors up-regulate excitatory amino acid transporters in mouse
      astrocytes.
AB  - BACKGROUND AND PURPOSE: Astrocytic excitatory amino acid transporters (EAATs)
      regulate extracellular glutamate concentrations and play a role in preventing
      neuroexcitotoxicity. As the delta-opioid receptor (DOP receptor) is
      neuroprotective against excitotoxic injury, we determined whether DOP receptor
      activation up-regulates EAAT expression and function. EXPERIMENTAL APPROACH: We
      measured mRNA and protein expression of EAAT1, EAAT2 and EAAT3 in cultured mouse
      astrocytes exposed to a specific DOP receptor agonist (UFP-512) with or without a
      DOP receptor antagonist, DOP receptor siRNA or inhibitors of PKC, PKA, PI3K, p38,
      MAPK, MEK and ERK, and evaluated the function of EAATs by measuring glutamate
      uptake. KEY RESULTS: Astrocytic DOP receptor mRNA and protein were suppressed by
      DOP receptor siRNA knockdown. DOP receptor activation increased mRNA and protein
      expression of EAAT1 and EAAT2, but not EAAT3, thereby enhancing glutamate uptake
      of astrocytes. DOP receptor-induced EAAT1 and EAAT2 expression was largely
      reversed by DOP receptor antagonist naltrindole or by DOP receptor siRNA
      knockdown, and suppressed by inhibitors of MEK, ERK and p38. DOP receptor
      accelerated glutamate uptake was inhibited by EAAT blockers, DOP receptor siRNA
      knockdown or inhibitors of MEK, ERK or p38. In contrast, inhibitors of PKA, PKC
      or PI3K had no significant effect on DOP receptor-induced EAAT expression.
      CONCLUSIONS AND IMPLICATIONS: DOP receptor activation up-regulates astrocytic
      EAATs via MEK-ERK-p38 signalling, suggesting a critical role for DOP receptors in
      the regulation of astrocytic EAATs and protection against neuroexcitotoxicity. As
      decreased EAAT expression contributes to pathophysiology in many neurological
      diseases, including amyotrophic lateral sclerosis, our findings present a new
      platform for potential treatments of these diseases.

PMID- 25052199
TI  - Utility of multi-detector tomography angiography with equivocal exercise stress
      test in acute coronary syndrome.

PMID- 25052198
TI  - The development of scales to measure childhood cancer survivors' readiness for
      transition to long-term follow-up care as adults.
AB  - PURPOSE: To develop and validate scales to measure constructs that survivors of
      childhood cancer report as barriers and/or facilitators to the process of
      transitioning from paediatric to adult-oriented long-term follow-up (LTFU) care.
      METHODS: Qualitative interviews provided a dataset that were used to develop
      items for three new scales that measure cancer worry, self-management skills and
      expectations about adult care. These scales were field-tested in a sample of 250
      survivors aged 15-26 years recruited from three Canadian hospitals between July
      2011 and January 2012. Rasch Measurement Theory (RMT) analysis was used to
      identify the items that represent the best indicators of each scale using tests
      of validity (i.e. thresholds for item response options, item fit statistics, item
      locations, differential item function) and reliability (Person Separation Index).
      Traditional psychometric tests of measurement performance were also conducted.
      RESULTS: RMT led to the refinement of a 6-item Cancer Worry scale (focused on
      worry about cancer-related issues such as late effects), a 15-item Self
      Management Skills scale (focused on skills an adolescent needs to acquire to
      manage their own health care), and a 12-item Expectations scale (about the nature
      of adult LTFU care). Our study provides preliminary evidence about the
      reliability and validity of these new scales (e.g. Person Separation Index >=
      0.81; Cronbach's alpha >= 0.81; test-retest reliability >= 0.85). CONCLUSION:
      There is limited knowledge about the transition experience of childhood cancer
      survivors. These scales can be used to investigate barriers survivors face in the
      process of transition from paediatric to adult care.

PMID- 25052200
TI  - DNA-RNA hybrid duplexes with decreasing pyrimidine content in the DNA strand
      provide structural snapshots for the A- to B-form conformational transition of
      nucleic acids.
AB  - DNA-RNA hybrids are heterogeneous nucleic acid duplexes consisting of a DNA
      strand and a RNA strand, and are formed as key intermediates in many important
      biological processes. They serve as substrates for the RNase H enzymatic
      activity, which has been exploited for several biomedical technologies such as
      antiviral and antisense therapies. To understand the relation of structural
      properties with the base composition in DNA-RNA hybrids, molecular dynamics (MD)
      simulations were performed on selected model systems by systematically varying
      the deoxypyrimidine (dPy) content from 0 to 100% in the DNA strand. The results
      suggest that the hybrid duplex properties are highly dependent on their
      deoxypyrimidine content of the DNA strand. However, such variations are not seen
      in their corresponding pure DNA and RNA duplex counterparts. It is also noticed
      that the systematic variation in deoxypyrimidine content of hybrids leads to
      gradual transformation between B- and A-form nucleic acid structures. Binding
      free energy calculations explain the previous experimental findings that the
      hybrids with high deoxypyrimidine content (>50%) are more stable than their
      respective pure counterparts. Pseudorotation angles, minor groove widths,
      phosphodiester angles, and glycosidic dihedral angles exhibit gradual A- to A/B
      like conformation with decreasing deoxypyrimidine content. Based on extensive
      analysis, possible factors that affect RNase H enzymatic activity on hybrid
      duplexes with high dPy composition are proposed. 

PMID- 25052201
TI  - Detection of flavor compounds in longissimus muscle from four hybrid pig breeds
      of Sus scrofa, Bamei pig, and Large White.
AB  - To detect the flavor quality and flavor compounds in raw longissimus muscle from
      four typical pig breeds: Sus scrofa * Bamei pig named F1 (group A), F1 * F1
      (group B), F1 * Bamei pig (group C), and F1 * Large White (group D). The chemical
      compositions of longissimus muscles from four breeds were examined using
      headspace solid-phase microextraction/gas chromatography mass spectrometry
      method. Distinct differences for the same flavor compounds of longissimus muscles
      between different breeds were analyzed. Totally 64 flavor compounds shared in
      four groups, and 10 flavor compounds with significant difference among four
      groups (p < 0.05), including allyl butyrate, (Z)-2-penten-1-ol, 2,2-dimethyl-3
      methyl oxirane, 2-pentylfuran, dodecane, 2,4-decadienal, vinylsilane, 3-methyl-1
      butanol, (1-methyldecyl)-benzene, and dipropyl phthalate. Totally, 23-41 flavor
      compounds did not commonly exist in four groups, such as only as dibutyl
      isophthalate in group A; 6,10-dimethyl-5-9-undecadien-2 one, bis (2
      trimethylsilyl) ethyl ester-malonic acid, heptadecane, 2,4,6-trimethyl pyridine,
      and diisooctyl adipate in group C alone; and 1,3-dimethylcyclopentanol, 2
      octanone, and trimethylsilane in group D alone. While, no specific flavor
      compounds were identified in group B. All these flavor compounds covered 12 types
      of hydrocarbons, alcohols, aldehydes, hydroxybenzenes, acids, ketones, esters,
      sulfides, furans, alkenes, and pyrrole. Besides, we analyzed 14 flavor compounds
      with different flavors combining with previous studies. The flavor compounds in
      longissimus muscles might be closely related to the breeds, and the hybrid of S.
      scrofa * Bamei pig had the most flavor compounds in raw longissimus muscle.

PMID- 25052202
TI  - Molecular isothermal techniques for combating infectious diseases: towards low
      cost point-of-care diagnostics.
AB  - Nucleic acid amplification techniques such as PCR have facilitated rapid and
      accurate diagnosis in central laboratories over the past years. PCR-based
      amplifications require high-precision instruments to perform thermal cycling
      reactions. Such equipment is bulky, expensive and complex to operate. Progressive
      advances in isothermal amplification chemistries, microfluidics and detectors
      miniaturisation are paving the way for the introduction and use of compact
      'sample in-results out' diagnostic devices. However, this paradigm shift towards
      decentralised testing poses diverse technological, economic and organizational
      challenges both in industrialized and developing countries. This review describes
      the landscape of molecular isothermal diagnostic techniques for infectious
      diseases, their characteristics, current state of development, and available
      products, with a focus on new directions towards point-of-care applications. 

PMID- 25052205
TI  - Dynamic density functional theory of protein adsorption on polymer-coated
      nanoparticles.
AB  - We present a theoretical model for the description of the adsorption kinetics of
      globular proteins onto charged core-shell microgel particles based on Dynamic
      Density Functional Theory (DDFT). This model builds on a previous description of
      protein adsorption thermodynamics [Yigit et al., Langmuir, 2012, 28], shown to
      well interpret the available calorimetric experimental data of binding isotherms.
      In practice, a spatially-dependent free-energy functional including the same
      physical interactions is built, and used to study the kinetics via a generalised
      diffusion equation. To test this model, we apply it to the case study of lysozyme
      adsorption on PNIPAM coated nanoparticles, and show that the dynamics obtained
      within DDFT is consistent with that extrapolated from experiments. We also
      perform a systematic study of the effect of various parameters in our model, and
      investigate the loading dynamics as a function of proteins' valence and
      hydrophobic adsorption energy, as well as their concentration and that of the
      nanoparticles. Although we concentrated here on the case of adsorption for a
      single protein type, the model's generality allows to study multi-component
      system, providing a reliable instrument for future studies of competitive and
      cooperative adsorption effects often encountered in protein adsorption
      experiments. 

PMID- 25052203
TI  - Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and
      microglia activation and prevents demyelination in experimental autoimmune
      encephalomyelitis in mice.
AB  - In the present study, we evaluated stimulation of the angiotensin type 2 receptor
      (AT2R) by the selective non-peptide agonist Compound 21 (C21) as a novel
      therapeutic concept for the treatment of multiple sclerosis using the model of
      experimental autoimmune encephalomyelitis (EAE) in mice. C57BL-6 mice were
      immunized with myelin-oligodendrocyte peptide and treated for 4 weeks with C21
      (0.3 mg/kg/day i.p.). Potential effects on myelination, microglia and T-cell
      composition were estimated by immunostaining and FACS analyses of lumbar spinal
      cords. The in vivo study was complemented by experiments in aggregating brain
      cell cultures and microglia in vitro. In the EAE model, treatment with C21
      ameliorated microglia activation and decreased the number of total T-cells and
      CD4+ T-cells in the spinal cord. Fluorescent myelin staining of spinal cords
      further revealed a significant reduction in EAE-induced demyelinated areas in
      lumbar spinal cord tissue after AT2R stimulation. C21-treated mice had a
      significantly better neurological score than vehicle-treated controls. In
      aggregating brain cell cultures challenged with lipopolysaccharide (LPS) plus
      interferon-gamma (IFNgamma), AT2R stimulation prevented demyelination,
      accelerated re-myelination and reduced the number of microglia. Cytokine
      synthesis and nitric oxide production by microglia in vitro were significantly
      reduced after C21 treatment. These results suggest that AT2R stimulation protects
      the myelin sheaths in autoimmune central nervous system inflammation by
      inhibiting the T-cell response and microglia activation. Our findings identify
      the AT2R as a potential new pharmacological target for demyelinating diseases
      such as multiple sclerosis. 

PMID- 25052206
TI  - Identification of Indole Alkaloid Structural Units Important for Stimulus
      Selective TRPM8 Inhibition: SAR Study of Naturally Occurring Iboga Derivatives.
AB  - The iboga alkaloid voacangine (1) has been reported previously to be the first
      stimulus-selective TRPM8 antagonist. In the present report, a structure-activity
      relationship (SAR) study is described on the effects of some naturally occurring
      indole alkaloid analogues on TRPM8 inhibition. Dihydrocatharanthine (10) and
      catharanthine (11) were found to be inhibitors of TRPM8 activity, and their IC50
      values were equivalent to that of BCTC, a potent and representative TRPM8
      antagonist. Furthermore, it was shown that the iboga moiety is the most crucial
      unit for TRPM8 blockade and that its stereostructure, as found in 1 but not in 10
      and 11, is essential for chemical agonist-selective TRPM8 inhibition. These
      findings should provide useful information for synthesizing additional stimulus
      selective and TRPM8-selective blockers. 

PMID- 25052207
TI  - Turoctocog alfa for the treatment of hemophilia a.
AB  - Hemophilia A (HA) represents one of the most common genetic bleeding disorders
      worldwide and results from a deficiency in factor VIII (FVIII). The mainstay of
      treatment for HA is repletion of FVIII. Numerous plasma-derived and recombinant
      factor concentrates are available, each with clinical advantages and
      disadvantages. Nonfactor products including desmopressin and antifibrinolytic
      agents can also be used, depending on the clinical situation and severity of
      FVIII deficiency. Turoctocog alfa is the most recent addition to recombinant
      FVIII concentrates available for the treatment of HA. Pharmacokinetic trials in
      animals and humans have demonstrated characteristics similar to those of other
      recombinant FVIII concentrates. Clinical trials have supported efficacy and
      safety in the management of HA in treatment-experienced patients; study results
      of turoctocog alfa in treatment-naive patients are pending. A smaller study in
      hemophilic patients undergoing surgery has demonstrated positive results.
      Although turoctocog alfa was approved by the U.S. Food and Drug Administration in
      2013, it will not be available on the market until 2015. Turoctocog alfa appears
      to be a safe and effective alternative to currently available recombinant FVIII
      concentrates; however, its place in therapy among these products has yet to be
      elucidated. 

PMID- 25052208
TI  - Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine
      prospects.
AB  - Although a number of fungal species belonging to the genus Candida can cause
      acute vulvovaginal infection (VVC), Candida albicans is by far the most prevalent
      etiological agent, particularly for the most severe chronic condition known as
      recurrent vulvovaginal candidiasis (RVVC). This review focuses on recent advances
      in pathogenic mechanisms and host immune responses to C. albicans and on the
      utilisation of this information in the development of a vaccine to prevent and/or
      treat vaginal candidiasis. Currently, two vaccines with main or sole RVVC as
      clinical indication have completed a phase 1 clinical trial, and one of them has
      entered a phase 2 trial.

PMID- 25052210
TI  - Answer to the letter to the editor of S. Negrini et al. concerning "active self
      correction and task-oriented exercises reduce spinal deformity and improve
      quality of life in subjects with mild adolescent idiopathic scoliosis. Results of
      a randomised controlled trial" by Monticone M, Ambrosini E, Cazzaniga D, Rocca B,
      Ferrante S (2014) Eur Spine J; DOI 10.1007/s00586-014-3241-y.

PMID- 25052212
TI  - Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in
      cells.
AB  - Mcl-1 is overexpressed in many cancers and can confer resistance to cell-death
      signaling in refractory disease. Molecules that specifically inhibit Mcl-1 hold
      potential for diagnosing and disrupting Mcl-1-dependent cell survival. We
      selected three peptides from a yeast-surface display library that showed moderate
      specificity and affinity for binding to Mcl-1 over Bfl-1, Bcl-xL, Bcl-2, and Bcl
      w. Specificity for Mcl-1 was improved by introducing threonine at peptide
      position 2e. The most specific peptide, MS1, bound Mcl-1 with 40-fold or greater
      specificity over four other human Bcl-2 paralogs. In BH3 profiling assays, MS1
      caused depolarization in several human Mcl-1-dependent cell lines with EC50
      values of ~3 MUM, contrasted with EC50 values of >100 MUM for Bcl-2-, Bcl-xL-, or
      Bfl-1-dependent cell lines. MS1 is at least 30-fold more potent in this assay
      than the previously used Mcl-1 targeting reagent NoxaA BH3. These peptides can be
      used to detect Mcl-1 dependency in cells and provide leads for developing Mcl-1
      targeting therapeutics. 

PMID- 25052213
TI  - Primary Gleason grade 4 at the positive margin is associated with metastasis and
      death among patients with Gleason 7 prostate cancer undergoing radical
      prostatectomy.
AB  - BACKGROUND: The presence of a positive surgical margin (PSM) at radical
      prostatectomy (RP) has been linked to an increased risk of biochemical recurrence
      and receipt of secondary therapy; however, its association with other oncologic
      end points remains controversial. OBJECTIVE: To evaluate the association of
      primary Gleason grade (GG) at the site of PSM with subsequent clinical
      progression and mortality among patients with Gleason score (GS) 7 prostate
      cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: We identified 1036 patients who
      underwent RP between 1996 and 2002. A single uropathologist re-reviewed all
      specimens noted to have a PSM to record GG at the margin. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: Survival was estimated using the Kaplan-Meier method.
      Cox models were used to analyze the association of margin primary GG with
      outcome. RESULTS AND LIMITATIONS: Overall, 338 men (33%) had a PSM; of those, 242
      had PSM GG3 and 96 had PSM GG4. Median postoperative follow-up was 13 yr.
      Compared with men with PSM GG3 or a negative SM, we noted that men with PSM GG4
      had significantly worse 15-yr systemic progression-free survival (74% vs. 90% vs.
      93%, respectively; p<0.001) and cancer-specific survival (86% vs. 96% vs. 97%,
      respectively; p=0.002). On multivariable analysis, the presence of PSM GG4 was
      associated with increased risks of systemic progression (hazard ratio [HR]: 2.77;
      p=0.003) and death from PCa (HR: 3.93; p=0.02) among men with a PSM. Limitations
      include the relatively small rate of disease recurrence. CONCLUSIONS: PSM primary
      GG4 was independently associated with adverse oncologic outcomes among men with
      GS7 PCa. Pending external validation, GG at the PSM may be considered for
      inclusion in pathologic reports and risk stratification following RP. PATIENT
      SUMMARY: Among patients with Gleason grade 7 prostate cancer and a positive
      surgical margin at the time of prostatectomy, we found that higher Gleason grade
      at the margin was associated with worse oncologic outcomes.

PMID- 25052214
TI  - The investigation of nanotribology of UHMWPE in fluid using atomic force
      microscopy.
AB  - The fundamental understanding of the nanowear behavior of ultrahigh molecular
      weight polyethylene (UHMWPE) at a nanometer scale needs to be achieved to provide
      a better understanding of the initiating wear process and the potential causes of
      the wear particles generation of joint replacement. A nanotribology study was
      performed using atomic force microscope (AFM) tips sliding against UHMWPE
      surfaces in both water and bovine serum lubricants. Frictional properties of the
      nanocontact, and the geometry and mechanical features of the resulting scratches
      have been quantitatively characterized using AFM lateral force and PeakForce QNM
      modes. The results in this work indicated that the friction force and friction
      coefficient were smaller in serum lubricant than that in water. A normal load of
      120 nN was the transition point for the plastic deformation of the material. The
      plastic deformation and material accumulation evolute with the increase of
      applied normal loads. Material pileup formed at the edges of the scratch, but
      they were not symmetrical due to the asymmetrical geometry of the silicon AFM
      tip. The height of the material pileup on the right side was approximately 40-70%
      of the pileup on the left side. The information may be useful for developing
      strategies for surface finishing techniques, which can control and minimize the
      production of asymmetric asperity and the resulting pileup with particular
      features. Furthermore, the moduli of the pileups were much larger than that of
      the fresh UHMWPE, which had the moduli greater than those of the inner scratch
      area. This suggested that stress concentration at these points could cause the
      pileup to be more susceptible to further wear processes, and eventually result in
      detaching from the bulk material.

PMID- 25052216
TI  - 3-D medical animation could be helpful tool for integration of medical
      curriculum.

PMID- 25052215
TI  - Outcomes of shipped live donor kidney transplants compared with traditional
      living donor kidney transplants.
AB  - The disparity between kidney transplant candidates and donors necessitates
      innovations to increase organ availability. Transporting kidneys allows for
      living donors and recipients to undergo surgery with a familiar transplant team,
      city, friends, and family. The effect of shipping kidneys and prolonged cold
      ischemia time (CIT) with living donor transplantation outcomes is not clearly
      known. This retrospective matched (age, gender, race, and year of procedure)
      cohort study compared allograft outcomes for shipped live donor kidney
      transplants and nonshipped living donor kidney transplants. Fifty-seven shipped
      live donor kidneys were transplanted from 31 institutions in 26 cities. The mean
      shipping distance was 1634 miles (range 123-2811) with mean CIT of 12.1 +/- 2.8
      h. The incidence of delayed graft function in the shipped cohort was 1.8% (1/57)
      compared to 0% (0/57) in the nonshipped cohort. The 1-year allograft survival was
      98% in both cohorts. There were no significant differences between the mean serum
      creatinine values or the rates of serum creatinine decline in the immediate
      postoperative period even after adjusted for gender and differences in recipient
      and donor BMI. Despite prolonged CITs, outcomes for shipped live donor kidney
      transplants were similar when compared to matched nonshipped living donor kidney
      transplants. 

PMID- 25052217
TI  - Comparison of the therapeutic efficacy of intravenous dimenhydrinate and
      intravenous piracetam in patients with vertigo: a randomised clinical trial.
AB  - BACKGROUND: The present study aimed to compare the therapeutic efficacy of
      dimenhydrinate and piracetam in patients with vertigo. METHODS: A blinded,
      parallel group, superiority, randomised clinical trial was carried out on
      patients who presented to the emergency department (ED) with vertigo. Healthy
      adult patients presenting to the ED with undifferentiated vertigo were included
      in the study. The efficacy of intravenous dimenhydrinate (100 mg) and intravenous
      piracetam (2000 mg) for reducing the intensity of vertigo was compared in two
      randomised treatment groups using a 10-point numeric rating scale (NRS). The
      determination of NRS scores was performed at presentation and at the 30th minute
      of presentation, after the study drug was implemented, both in immobile and
      ambulatory positions. The primary outcome variable was reduction in vertigo
      intensity documented on the NRS at the 30th minute after medication
      administration, analysed by intention to treat. RESULTS: A total of 94 patients
      were included in the randomisation (n=47 in both groups). The baseline NRS scores
      were 7.55+/-2.00 in the dimenhydrinate group and 8.19+/-1.79 in the piracetam
      group. The changes from baseline for dimenhydrinate and piracetam were 2.92+/
      3.11 and 3.75+/-3.40 (difference -0.83 (95% CI -2.23 to 0.57)) in the immobile
      position and were 2.04+/-3.07 and 2.72+/-2.91 (difference -0.68 (95% CI -2.03 to
      0.67)) in the ambulatory position. Rescue medication need was similar in both
      treatment groups (p=0.330), and only one adverse reaction was reported.
      CONCLUSIONS: We found no evidence of a difference between dimenhydrinate and
      piracetam in relieving the symptoms of vertigo. TRIAL REGISTRATION NUMBER:
      Clinical Trials Registration ID: NCT01890538.

PMID- 25052218
TI  - Efficacy of the jet injector in local anaesthesia for small wound sutures: a
      randomised clinical trial compared with the needle infiltration technique.
AB  - BACKGROUND: Despite advances in the application of needle free devices in medical
      procedure, there is a paucity of knowledge on the efficacy of the jet injector
      for suturing skin wounds. AIMS: Our study aimed to compare the severity of pain
      and time to initiation of anaesthesia between two methods of local anaesthesia
      for skin suturing of small facial wounds. METHODS: We conducted a double blind
      randomised clinical trial between December 2012 and February 2013 at a university
      hospital in Tehran, Iran. 53 patients with small facial wounds needing skin
      closure with sutures were assigned to either the jet injection group or the
      needle infiltration group. Pain severity after administration of local
      anaesthesia and during the stitching procedure, and time to initiation of skin
      numbness were evaluated. RESULTS: Mean pain score during the anaesthetic
      procedure was 1.1+/-1 in the jet injector group compared with 4.4+/-1.4 in the
      needle infiltration group (p<0.0001). Moreover, time to initiation of local
      numbness was significantly longer in the jet injection group than in the needle
      infiltration group (p<0.0001). Nevertheless, suture procedure related pain scores
      did not differ significantly between the two groups (p>0.05). CONCLUSIONS: The
      jet injector is an effective device in reducing the pain of the anaesthetic
      procedure for small facial wounds. However, the remarkably lower pain should be
      evaluated in light of other parameters, including acceptance and preference of
      the newly introduced technique. TRIAL REGISTRATION NO: IRCT201201308872N3.

PMID- 25052219
TI  - Joint toxicity of chlorpyrifos and endosulfan to Pacific treefrog (Pseudacris
      regilla) tadpoles.
AB  - Recent ecotoxicology studies have focused on the potential interaction of
      pesticides and the effects these interactions may have on aquatic ecosystems. We
      examined the combined effects of two insecticides, endosulfan and chlorpyrifos,
      that have been previously examined individually on survival, growth, and
      development of Pacific treefrog (Pseudacris regilla) tadpoles. Historically, both
      pesticides have been heavily used in the Central Valley of California, been
      identified in downwind montane areas, and are highly toxic to amphibian larvae.
      Tadpoles were exposed to chlorpyrifos and endosulfan individually and in
      combination from Gosner stage 25 through metamorphosis to evaluate the individual
      effects and the interaction between these insecticides. Chlorpyrifos alone did
      not affect survival or body size after 30 days, even at concentrations greater
      than the previously reported LC50. Survival and body size decreased with
      increasing endosulfan concentrations. The interactive effects of the insecticides
      depended on concentration and exposure duration. In combination, 137 ug/L
      chlorpyrifos inhibited the negative effects of endosulfan on growth and survival.
      The presence of both insecticides in combination facilitated the development of
      axial malformations. In the presence of endosulfan with either 266 or 394 ug/L
      chlorpyrifos, malformations occurred in 33 and 87 % of tadpoles, respectively.
      Our results indicate that organophosphorus and organochlorine pesticides with
      different modes of action can result in varying interactions depending on their
      concentrations and on the end points being assessed. Further examination of
      contaminant impacts on natural aquatic systems should continue to focus on the
      effects of multiple contaminants and their potential for unpredictable,
      nonadditive interactions. 

PMID- 25052220
TI  - Ovarian nutritional resources during the reproductive cycle of the hematophagous
      Dipetalogaster maxima (Hemiptera: Reduviidae): focus on lipid metabolism.
AB  - In this study, we have analyzed the changes of the ovarian nutritional resources
      in Dipetalogaster maxima at representative days of the reproductive cycle:
      previtellogenesis, vitellogenesis, as well as fasting-induced early and late
      atresia. As expected, the amounts of ovarian lipids, proteins, and glycogen
      increased significantly from previtellogenesis to vitellogenesis and then,
      diminished during atresia. However, lipids and protein stores found at the
      atretic stages were higher in comparison to those registered at
      previtellogenesis. Specific lipid staining of ovarian tissue sections evidenced
      remarkable changes in the shape, size, and distribution of lipid droplets
      throughout the reproductive cycle. The role of lipophorin (Lp) as a yolk protein
      precursor was analyzed by co-injecting Lp-OG (where OG is Oregon Green) and Lp
      DiI (where DiI is 1,10-dioctadecyl-3,3,30,30-tetramethylindocarbocyanine) to
      follow the entire particle, demonstrating that both probes colocalized mainly in
      the yolk bodies of vitellogenic oocytes. Immunofluorescence assays also showed
      that Lp was associated to yolk bodies, supporting its endocytic pathway during
      vitellogenesis. The involvement of Lp in lipid delivery to oocytes was
      investigated in vivo by co-injecting fluorescent probes to follow the fate of the
      entire particle (Lp-DiI) and its lipid cargo (Lp-Bodipy-FA). Lp-DiI was readily
      incorporated by vitellogenic oocytes and no lipoprotein uptake was observed in
      terminal follicles of ovaries at atretic stages. Bodipy-FA was promptly
      transferred to vitellogenic oocytes and, to a much lesser extent, to
      previtellogenic follicles and to oocytes of ovarian tissue at atretic stages.
      Colocalization of Lp-DiI and Lp-Bodipy-FA inside yolk bodies indicated the
      relevance of Lp in the buildup of lipid and protein oocyte stores during
      vitellogenesis. 

PMID- 25052221
TI  - Provider perspectives on presenting risk information and managing worry about
      recurrence among breast cancer survivors.
AB  - BACKGROUND: Although worry about recurrence is a persistent concern among breast
      cancer survivors, little is known about physicians' confidence about presenting
      recurrence risk information, identifying women with considerable worry, and
      helping women manage worry. METHODS: Between January and June 2012, we surveyed
      750 surgeons and 750 medical oncologists randomly sampled from the American
      Medical Association Physician Masterfile. We tested differences between surgeons
      and medical oncologists on confidence of presenting risk, identifying and
      managing worry using chi-square statistic and Student's t-tests and developed
      multiple variable logistic regression models to explain odds regarding confidence
      and use of different strategies for managing worry. RESULTS: The analytic sample
      included 403 surgeons and 363 medical oncologists (n = 766; response rate = 60%).
      Compared with surgeons, medical oncologists were significantly more likely to
      report confidence in: presenting risk information (87.5% vs 73.2%), identifying
      women who are worried (74.1% vs 63.9%), and managing worry (66.9% vs 52.4%).
      Confidence in managing worry was associated with more regular inquiry about worry
      (p = 0.009). Models of the likelihood of using different management strategies
      varied by provider type (e.g., surgeons more likely than medical oncologists to
      recommend support group or online resources, oncologists more likely to refer to
      psychologist or use medications, all p < 0.05). CONCLUSION: Cancer providers,
      particularly surgeons, may benefit from educational training to raise confidence
      in identifying women with high levels of worry and managing women with
      considerable worry. Communication between specialties and primary care physicians
      on efforts to manage worry is necessary for coordinated, quality care for women
      with breast cancer.

PMID- 25052223
TI  - Preparation and electrochromatographic characterization of new chiral beta
      cyclodextrin poly(acrylamidopropyl) porous layer open tubular capillary columns.
AB  - A novel chiral stationary phase consisting of an amidopropyltrimethylammonium
      chloride divinylbenzene (APAT-DVB) polymer containing the chiral selector
      heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin (HSbetaCD) has been
      employed in porous layer open tubular (PLOT) capillary column format with various
      conditions evaluated to optimize the polymerization and chiral selector
      immobilization. Scanning electron microscopy demonstrated a near homogenous
      longitudinal open path in the column with a polymer film of uniform thickness. IR
      spectroscopy characterized the functional groups of the polymer and energy
      dispersive X-ray spectroscopy provided further evidence of the successful polymer
      modification with HSbetaCD. Optimum electrochromatographic separation conditions
      were elaborated with respect to organic solvent content and pH of the background
      electrolyte. Colum-to-column and long-term reproducibility was excellent. The
      effectiveness of the new capillary column was demonstrated with the successful
      separation of d-and l-aspartic acid, d- and l-tyrosine and d-and l-lysine. 

PMID- 25052222
TI  - Evaluation of community-based systems for the surveillance of day three-positive
      Plasmodium falciparum cases in Western Cambodia.
AB  - BACKGROUND: Delayed clearance of Plasmodium falciparum parasites is used as an
      operational indicator of potential artemisinin resistance. Effective community
      based systems to detect P. falciparum cases remaining positive 72 hours after
      initiating treatment would be valuable for guiding case follow-up in areas of
      known resistance risk and for detecting areas of emerging resistance. METHODS:
      Systems incorporating existing networks of village malaria workers (VMWs) to
      monitor day three-positive P. falciparum cases were piloted in three provinces in
      western Cambodia. Quantitative and qualitative data were used to evaluate the
      wider feasibility and sustainability of community-based surveillance of day three
      positive P. falciparum cases. RESULTS: Of 294 day-3 blood slides obtained across
      all sites (from 297 day-0 positives), 63 were positive for P. falciparum, an
      overall day-3 positivity rate of 21%. There were significant variations in the
      systems implemented by different partners. Full engagement of VMWs and health
      centre staff is critical. VMWs are responsible for a range of individual tasks
      including preparing blood slides on day-0, completing forms, administering
      directly observed therapy (DOT) on days 0-2, obtaining follow-up slides on day-3
      and transporting slides and paperwork to their supervising health centre. When
      suitably motivated, unsalaried VMWs are willing and able to produce good quality
      blood smears and achieve very high rates of DOT and day-3 follow-up. CONCLUSIONS:
      Community-based surveillance of day-3 P. falciparum cases is feasible, but highly
      intensive, and as such needs strong and continuous support, particularly
      supervision and training. The purpose and role of community-based day-3
      surveillance should be assessed in the light of resource requirements; scaling-up
      would need to be systematic and targeted, based on clearly defined
      epidemiological criteria. To be truly comprehensive, the system would need to be
      extended beyond VMWs to other public and private health providers.

PMID- 25052225
TI  - Prostate cancer: review in 2014.
AB  - Recent advances need to be highlighted in the management of both localized and
      metastatic prostate cancer. New early detection and molecular characterization
      tools are being developed to improve differentiation of their progression
      profiles and reduce "overdetection" and "overtreatment" of clinically
      "insignificant" cancers. In addition, the development of multi-parametric MR has
      improved the characterization of localized cancer and introduced the new concept
      of focal treatment. Finally, several treatments for metastatic cancer which is
      resistant to castration have recently increased the therapeutic armamentarium. 

PMID- 25052224
TI  - Biomarker-based treatment selection in early-stage rectal cancer to promote organ
      preservation.
AB  - BACKGROUND: Total mesorectal excision (TME) remains commonplace for T1-2 rectal
      cancer owing to fear of undertreating a small proportion of patients with node
      positive disease. Molecular stratification may predict cancer progression. It
      could be used to select patients for organ-preserving surgery if specific
      biomarkers were validated. METHODS: Gene methylation was quantified using
      bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS
      mutation and microsatellite instability status were also defined. Molecular
      parameters were correlated with histopathological indices of disease progression.
      Predictive models for nodal metastasis, lymphovascular invasion (LVI) and distant
      metastasis were constructed using a multilevel reverse logistic regression model.
      RESULTS: Methylation of the retinoic acid receptor beta gene, RARB, and that of
      the checkpoint with forkhead and ring finger gene, CHFR, was associated with
      tumour stage (RARB: 51.9 per cent for T1-2 versus 33.9 per cent for T3-4, P <
      0.001; CHFR: 5.5 per cent for T1-2 versus 12.6 per cent for T3-4, P = 0.005).
      Gene methylation associated with nodal metastasis included RARB (47.1 per cent
      for N- versus 31.7 per cent for N+; P = 0.008), chemokine ligand 12, CXCL12 (12.3
      per cent for N- versus 8.9 per cent for N+; P = 0.021), and death-associated
      protein kinase 1, DAPK1 (19.3 per cent for N- versus 12.3 per cent for N+; P =
      0.022). RARB methylation was also associated with LVI (45.1 per cent for LVI-
      versus 31.7 per cent for LVI+; P = 0.038). Predictive models for nodal metastasis
      and LVI achieved sensitivities of 91.1 and 85.0 per cent, and specificities of
      55.3 and 45.3 per cent, respectively. CONCLUSION: This methylation biomarker
      panel provides a step towards accurate discrimination of indolent and aggressive
      rectal cancer subtypes. This could offer an improvement over the current standard
      of care, whereby fit patients are offered radical surgery.

PMID- 25052226
TI  - The influence of socioeconomic factors and family context on energy-dense food
      consumption among 2-year-old children.
AB  - BACKGROUND/OBJECTIVES: Adverse effect on health has been described for a high
      consumption of energy-dense food, among children and adults. Limited research has
      been performed among pre-school children. The objective of this study is to
      evaluate the association between socioeconomic characteristics and family
      structure, and the consumption of energy-dense food among 2-year-old children.
      SUBJECTS/METHODS: The study sample includes 808 2-year-old children from the
      Portuguese birth cohort Generation XXI with information on food consumption. Data
      were obtained from questionnaires administered by interviewers to parents. Based
      on a food frequency questionnaire, four groups of energy-dense food were defined:
      soft drinks (sweetened drinks), sweets (chocolate and candies), cakes (creamy and
      not creamy cakes and sweet pastry) and salty snacks (crisps, pizza and burger).
      Multinomial logistic regression models (odds ratio and 95% confidence intervals)
      were fitted to estimate the associations. RESULTS: Intakes of energy-dense food
      were much lower than in similar aged children in other Westernized countries.
      Maternal age and education, grandparents' education, household income and
      maternal occupation were inversely associated with the consumption of energy
      dense food, particularly soft drinks and sweets. Children with older siblings
      were more likely to have a daily consumption of any energy-dense food. Few
      significant associations were found between socioeconomic characteristics and
      family structure and consumption of cakes and sweets less than once a week.
      CONCLUSION: High socioeconomic characteristics were associated with lower
      consumption of energy-dense food by 2-year-old children, mainly soft drinks and
      sweets. This influence is not only from parents' background but also from the
      preceding generations.

PMID- 25052228
TI  - Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans.
AB  - BACKGROUND/OBJECTIVES: The short chain fatty acid acetate (AC), may have a role
      in increasing insulin sensitivity, thus lowering risk for obesity and type 2
      diabetes mellitus. It is unclear if AC kinetics is similar in normal (NI) and
      hyperinsulinaemic (HI) participants. Therefore, we studied AC absorption from the
      distal colon in participants with normal (<40 pmol/l) and high (>=40 pmol/l)
      plasma insulin. This work was a part of a series of studies conceived to compute
      a kinetic model for AC. Kinetic parameters such as estimates of rate of entry
      into peripheral blood, hepatic uptake and endogenous/exogenous production were
      compared in the groups. SUBJECTS/METHODS: Overnight fasted NI (n=9) and HI (n=8)
      participants were given rectal infusions containing sodium AC (90 mmol/l). The
      solutions were retained for 40 min, then voided for AC measurement. Total amount
      of AC infused was 27 mmols. RESULTS: AC absorption from the distal colon (279+/
      103 vs 322+/-91 MUmol/min, P=0.76) and hepatic uptake of AC (155+/-101 vs 146+/
      85 MUmol/min, P=0.94) were similar in the groups. Endogenous and exogenous AC
      production was significantly higher in NI than HI participants. Plasma AC was
      inversely proportional to plasma insulin concentrations in the entire cohort
      (y=k/x, where k=1813). CONCLUSIONS: There was low power to detect differences in
      AC absorption rate and hepatic AC uptake in NI vs HI. The rate of entry of AC
      into peripheral blood was similar in NI and HI participants. However,
      hyperinsulinaemia may alter endogenous and exogenous AC metabolism.

PMID- 25052227
TI  - Palmitic acid in the sn-2 position of dietary triacylglycerols does not affect
      insulin secretion or glucose homeostasis in healthy men and women.
AB  - BACKGROUND/OBJECTIVES: Dietary triacylglycerols containing palmitic acid in the
      sn-2 position might impair insulin release and increase plasma glucose.
      SUBJECTS/METHODS: We used a cross-over designed feeding trial in 53 healthy Asian
      men and women (20-50 years) to test this hypothesis by exchanging 20% energy of
      palm olein (PO; control) with randomly interesterified PO (IPO) or high oleic
      acid sunflower oil (HOS). After a 2-week run-in period on PO, participants were
      fed PO, IPO and HOS for 6 week consecutively in randomly allocated sequences.
      Fasting (midpoint and endpoint) and postprandial blood at the endpoint following
      a test meal (3.54 MJ, 14 g protein, 85 g carbohydrate and 50 g fat as PO) were
      collected for the measurement of C-peptide, insulin, glucose, plasma glucose
      dependent insulinotropic polypeptide and glucagon-like peptide-1, lipids and
      apolipoproteins; pre-specified primary and secondary outcomes were postprandial
      changes in C-peptide and plasma glucose. RESULTS: Low density lipoprotein
      cholesterol was 0.3 mmol/l (95% confidence interval (95% CI)) 0.1, 0.5; P<0.001)
      lower on HOS than on PO or IPO as predicted, indicating good compliance to the
      dietary intervention. There were no significant differences (P=0.58) between
      diets among the 10 male and 31 female completers in the incremental area under
      the curve (0-2 h) for C-peptide in nmol.120 min/l: GM (95% CI) were PO 220 (196,
      245), IPO 212 (190, 235) and HOS 224 (204, 244). Plasma glucose was 8% lower at 2
      h on IPO vs PO and HOS (both P<0.05). CONCLUSION: Palmitic acid in the sn-2
      position does not adversely impair insulin secretion and glucose homeostasis.

PMID- 25052229
TI  - Effects of probiotic supplementation over 5 months on routine haematology and
      clinical chemistry measures in healthy active adults.
AB  - Use of probiotic-containing foods and probiotic supplements is increasing;
      however, few studies document safety and tolerability in conjunction with defined
      clinical end points. This paper reports the effects of 150 days of
      supplementation with either a single- (Bifidobacterium animalis subsp. lactis Bl
      04) or a double-strain (Lactobacillus acidophilus NCFM and Bifidobacterium
      animalis subsp. lactis Bi-07) probiotic on routine haematology and clinical
      chemistry measures in healthy active adults. Pre- to post-intervention changes in
      laboratory measures were determined and compared between supplement and placebo
      groups. Overall there were few differences in routine haematology and clinical
      chemistry measures between supplement and placebo groups post-intervention.
      Exceptions included plasma calcium (P=0.03) and urea (P=0.015); however, observed
      changes were small and within assay-specific laboratory reference ranges. These
      data provide evidence supporting the use of these probiotic supplements over a
      period of 5 months in healthy active adults without obvious safety or
      tolerability issues.

PMID- 25052231
TI  - Evidence for weak genetic recombination at the PTP2 locus of Nosema ceranae.
AB  - The microsporidian Nosema ceranae is an emergent pathogen that threatens the
      health of honeybees and other pollinators all over the world. Its recent rapid
      spread across a wide variety of host species and environments demonstrated an
      enhanced ability of adaptation, which seems to contradict the lack of evidence
      for genetic recombination and the absence of a sexual stage in its life cycle.
      Here we retrieved fresh data of the patterns of genetic variation at the PTP2
      locus in naturally infected Apis mellifera colonies, by means of single genome
      amplification. This technique, designed to prevent the formation of chimeric
      haplotypes during polymerase chain reaction (PCR), provides more reliable
      estimates of the diversity levels and haplotype structure than standard PCR
      cloning methods. Our results are consistent with low but significant rates of
      recombination in the history of the haplotypes detected: estimates of the
      population recombination rate are of the order of 30 and support recent evidence
      for unexpectedly high levels of variation of the parasites within honeybee
      colonies. These observations suggest the existence of a diploid stage at some
      point in the life cycle of this parasite and are relevant for our understanding
      of the dynamics of its expanding population. 

PMID- 25052230
TI  - Dietary patterns derived with multiple methods from food diaries and breast
      cancer risk in the UK Dietary Cohort Consortium.
AB  - BACKGROUND/OBJECTIVES: In spite of several studies relating dietary patterns to
      breast cancer risk, evidence so far remains inconsistent. This study aimed to
      investigate associations of dietary patterns derived with three different methods
      with breast cancer risk. SUBJECTS/METHODS: The Mediterranean Diet Score (MDS),
      principal components analyses (PCA) and reduced rank regression (RRR) were used
      to derive dietary patterns in a case-control study of 610 breast cancer cases and
      1891 matched controls within four UK cohort studies. Dietary intakes were
      collected prospectively using 4- to 7-day food diaries and resulting food
      consumption data were grouped into 42 food groups. Conditional logistic
      regression models were used to estimate odds ratios (ORs) for associations
      between pattern scores and breast cancer risk adjusting for relevant covariates.
      A separate model was fitted for post-menopausal women only. RESULTS: The MDS was
      not associated with breast cancer risk (OR comparing first tertile with third
      1.20 (95% CI 0.92; 1.56)), nor the first PCA-derived dietary pattern, explaining
      2.7% of variation of diet and characterized by cheese, crisps and savoury snacks,
      legumes, nuts and seeds (OR 1.18 (95% CI 0.91; 1.53)). The first RRR-derived
      pattern, a 'high-alcohol' pattern, was associated with a higher risk of breast
      cancer (OR 1.27; 95% CI 1.00; 1.62), which was most pronounced in post-menopausal
      women (OR 1.46 (95% CI 1.08; 1.98)). CONCLUSIONS: A 'high-alcohol' dietary
      pattern derived with RRR was associated with an increased breast cancer risk; no
      evidence of associations of other dietary patterns with breast cancer risk was
      observed in this study.

PMID- 25052232
TI  - Placental pathology in early intrauterine growth restriction associated with
      maternal hypertension.
AB  - INTRODUCTION: To identify key pathological characteristics of placentas from
      pregnancies complicated by early intrauterine growth restriction, and to examine
      their relations with maternal hypertensive disease and umbilical artery Doppler
      waveform abnormalities. METHODS: Single-center retrospective cohort study of
      singleton pregnancies with abnormal umbilical artery Doppler flow patterns
      resulting in a live birth <34 weeks of a baby with a weight <10th percentile for
      gestational age. Umbilical artery end diastolic flow was classified as being
      either present or absent/reversed (AREDF). Data were stratified into intrauterine
      growth restriction with or without hypertensive disease and pathological
      characteristics were compared between these various conditions according to
      predefined scoring criteria. RESULTS: Among 164 placentas studied, we found high
      rates of characteristic histopathological features that were associated with
      intrauterine growth restriction, including infarction (>5% in 42%), chronic
      villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated
      nucleated red blood cells (89%), increased syncytial knotting (93%), increased
      villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia
      (35%). Chronic inflammation of fetal membranes and syncytial knotting were more
      common in women with concomitant hypertensive disease as compared to women with
      normotensive IUGR (p < 0.05). Placentas from women with umbilical artery AREDF
      were more likely to show increased numbers of nucleated red blood cells and
      distal villous hypoplasia (p < 0.05). DISCUSSION: Placentas of women with early
      IUGR show high rates of several histological aberrations. Further, concomitant
      maternal hypertension is associated with characteristic inflammatory changes and
      umbilical artery AREDF with signs of chronic hypoxia.

PMID- 25052233
TI  - Human uridine phosphorylase-1 inhibitors: a new approach to ameliorate 5
      fluorouracil-induced intestinal mucositis.
AB  - PURPOSE: 5-fluorouracil (5-FU) has been broadly used to treat solid tumors for
      more than 50 years. One of the major side effects of fluoropyrimidines therapy is
      oral and intestinal mucositis. Human uridine phosphorylase (hUP) inhibitors have
      been suggested as modulators of 5-FU toxicity. Therefore, the present study aimed
      to test the ability of hUP blockers in preventing mucositis induced by 5-FU.
      METHODS: We induced intestinal mucositis in Wistar rats with 5-FU, and the
      intestinal damage was evaluated in presence or absence of two hUP1 inhibitors
      previously characterized. We examined the loss of weight and diarrhea following
      the treatment, the villus integrity, uridine levels in plasma, and the neutrophil
      migration by MPO activity. RESULTS: We found that one of the compounds, 6-hydroxy
      4-methyl-1H-pyridin-2-one-3-carbonitrile was efficient to promote intestinal
      mucosa protection and to inhibit the hUP1 enzyme, increasing the uridine levels
      in the plasma of animals. However, the loss of body weight, diarrhea intensity or
      neutrophil migration remained unaffected. CONCLUSION: Our results bring support
      to the hUP1 inhibitor strategy as a novel possibility of prevention and treatment
      of mucositis during the 5-FU chemotherapy, based on the approach of uridine
      accumulation in plasma and tissues.

PMID- 25052234
TI  - Improved replication efficiency of echovirus 5 after transfection of colon cancer
      cells using an authentic 5' RNA genome end methodology.
AB  - Oncolytic virotherapy is a promising novel form of cancer treatment, but the
      therapeutic efficiency needs improvement. A potential strategy to enhance the
      therapeutic effect of oncolytic viruses is to use infectious nucleic acid as
      therapeutic agent to initiate an oncolytic infection, without administrating
      infectious viral particles. Here we demonstrate improved viral replication
      activation efficiency when transfecting cells with 5' end authentic in vitro
      transcribed enterovirus RNA as compared to genomic RNA with additional non
      genomic 5' nucleotides generated by conventional cloning methods. We used
      echovirus 5 (E5) as an oncolytoc model virus due to its ability to replicate in
      and completely destroy five out of six colon cancer cell lines and kill
      artificial colon cancer tumors (HT29 spheroids), as shown here. An E5 infectious
      cDNA clone including a hammerhead ribozyme sequence was used to generate in vitro
      transcripts with native 5' genome ends. In HT29 cells, activation of virus
      replication is approximately 20-fold more efficient for virus genome transcripts
      with native 5' genome ends compared to E5 transcripts generated from a standard
      cDNA clone. This replication advantage remains when viral progeny release starts
      by cellular lysis 22 h post transfection. Hence, a native 5' genomic end improves
      infection activation efficacy of infectious nucleic acid, potentially enhancing
      its therapeutic effect when used for cancer treatment. The clone design with a
      hammerhead ribozyme is likely to be applicable to a variety of oncolytic positive
      sense RNA viruses for the purpose of improving the efficacy of oncolytic
      virotherapy.

PMID- 25052235
TI  - Improvement in retinopathy of prematurity screening standards after the
      development of a multidisciplinary dedicated team.

PMID- 25052236
TI  - Multiple cervical lymph node involvement and extra-capsular extension predict for
      contralateral nodal recurrence after ipsilateral radiotherapy for squamous cell
      carcinoma of the tonsil.
AB  - BACKGROUND: Ipsilateral radiotherapy is an established technique for treating
      well-lateralised tonsillar tumours. Concerns exist regarding the risk of
      contralateral nodal failure, particularly in patients with ipsilateral nodal
      involvement at presentation. In this study, we retrospectively reviewed the
      clinical outcomes of patients treated with ipsilateral radiotherapy aiming to
      identify factors that predispose to a higher risk of contralateral nodal
      recurrence. METHODS: Retrospective case note review of all patients with
      tonsillar cancer who were treated using ipsilateral radiotherapy between
      September 1995 and September 2011 was performed. Demographics, T and N stage,
      involvement of soft palate and/or tongue base, presence of extra-capsular spread
      (ECS) and treatment details were recorded. Kaplan-Meier curves for treatment
      outcomes were generated. RESULTS: A total of 136 patients were identified. Median
      follow-up was 4.2years. Twelve (9%) patients had loco-regional recurrence. Eight
      patients (6%) had contralateral recurrence. N2b disease, ECS and number of pack
      years of smoking were associated with contralateral nodal recurrence. Five-year
      overall survival was 89%, loco-regional disease-free survival 90%, disease-free
      survival 86% and distal recurrence-free survival 96%. CONCLUSION: N2b disease,
      ECS and a greater than 10 pack-year smoking history are risk factors for
      contralateral nodal recurrence in well-lateralised tonsillar cancers.
      Prophylactic irradiation of the contralateral neck should be recommended in this
      group of patients.

PMID- 25052237
TI  - miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc
      finger E-box-binding homeobox 2 (ZEB2) expression.
AB  - This study was to investigate the effect of miR-200c on regulation of ovarian
      cancer cell metastasis potential and explore the underlying molecular events. qRT
      PCR was used to analyze the level of miR-200c expression in 48 ovarian cancer and
      30 normal ovarian tissue samples. pre-miR-200c was used to manipulate miR-200c
      expression in ovarian cancer cells for detection of changed phenotypes of tumor
      cells. Bioinformatics analysis was then used to predict target genes of miR-200c
      and GO and pathway analyses drew the miR-200c-related gene network. Luciferase
      reporter assay confirmed the target of miR-200c as ZEB2. Western blot was used to
      detect gene expressions in ovarian cancer cells. Level of miR-200c expression was
      much higher in ovarian cancer than in normal ovarian tissues, and miR-200c
      expression was inversely associated with advanced clinical stage and lymph node
      metastasis of ovarian cancer (p < 0.01). The database search predicted 186 miR
      200c-targeting genes, and GO analysis showed that functions of these target genes
      were enriched in the protein binding and other biological processes. Furthermore,
      miR-200c expression inhibited ovarian cancer cell ES-2 migration and invasion
      capacity by suppression of ZEB2 expression (p < 0.01). Overexpression of miR-200c
      regulated E-cadherin and vimentin expression in ovarian cancer cells. This study
      demonstrated high miR-200c expression in ovarian cancer tissues and ZEB2 as a
      targeting gene of miR-200c, which mediated the effects of miR-200c on regulation
      of ovarian cancer cell migration and invasion capacity and epithelial-to
      mesenchymal transition. Thus, targeting of miR-200c or ZEB2 may serve as a
      potential therapeutic strategy for control of ovarian cancer.

PMID- 25052238
TI  - Baclofen for stroke patients with persistent hiccups: a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: The results of preclinical studies suggest that baclofen may be
      useful in the treatment of stroke patients with persistent hiccups. This study
      was aimed to assess the possible efficacy of baclofen for the treatment of
      persistent hiccups after stroke. METHODS: In total, 30 stroke patients with
      persistent hiccups were randomly assigned to receive baclofen (n = 15) or a
      placebo (n = 15) in a double-blind, parallel-group trial. Participants in the
      baclofen group received 10 mg baclofen 3 times daily for 5 days. Participants
      assigned to the placebo group received 10 mg placebo 3 times daily for 5 days.
      The primary outcome measure was cessation of hiccups. Secondary outcome measures
      included efficacy in the two groups and adverse events. RESULTS: All 30 patients
      completed the study. The number of patients in whom the hiccups completely
      stopped was higher in the baclofen group than in the placebo group (relative
      risk, 7.00; 95% confidence interval, 1.91-25.62; P = 0.003). Furthermore,
      efficacy was higher in the baclofen group than in the placebo group (P < 0.01).
      No serious adverse events were documented in either group. One case each of mild
      transient drowsiness and dizziness was present in the baclofen group.
      CONCLUSIONS: Baclofen was more effective than a placebo for the treatment of
      persistent hiccups in stroke patients. TRIAL REGISTRATION: Chinese Clinical
      Trials Register: ChiCTR-TRC-13004554.

PMID- 25052239
TI  - Quantitative measurement of intact alpha-synuclein proteoforms from post-mortem
      control and Parkinson's disease brain tissue by intact protein mass spectrometry.
AB  - A robust top down proteomics method is presented for profiling alpha-synuclein
      species from autopsied human frontal cortex brain tissue from Parkinson's cases
      and controls. The method was used to test the hypothesis that pathology
      associated brain tissue will have a different profile of post-translationally
      modified alpha-synuclein than the control samples. Validation of the sample
      processing steps, mass spectrometry based measurements, and data processing steps
      were performed. The intact protein quantitation method features extraction and
      integration of m/z data from each charge state of a detected alpha-synuclein
      species and fitting of the data to a simple linear model which accounts for
      concentration and charge state variability. The quantitation method was validated
      with serial dilutions of intact protein standards. Using the method on the human
      brain samples, several previously unreported modifications in alpha-synuclein
      were identified. Low levels of phosphorylated alpha synuclein were detected in
      brain tissue fractions enriched for Lewy body pathology and were marginally
      significant between PD cases and controls (p = 0.03). 

PMID- 25052240
TI  - Nod and wave: an Internet study of the codeine intoxication phenomenon.
AB  - BACKGROUND: The non-medical use of pharmaceutical opioids such as codeine is of
      increasing public health concern. The aim of the study was to describe codeine
      intoxication experiences amongst recreational drug users, as posted on public
      Internet forums. METHODS: Internet searches were carried out by using the
      specific key word 'codeine' and in combination with 'experience', 'report',
      'trip' and 'forum'. 96 Trip reports and 156 thread discussions relating to the
      sole use of codeine were analysed using the empirical phenomenological
      psychological (EPP) method. Nine themes and 72 categories emerged. RESULTS:
      Narratives illustrated transitions between medical and non-medical use of codeine
      for dulling of emotional and/or physical pain, opiate withdrawal management and
      for intoxication. Codeine's appeal centred on access via family medicine
      cabinets, prescribers and pharmacies. Discussion and dissemination of indigenous
      harm reduction tactics included the learning to appreciate codeine's effect via
      moderated use in optimal settings, avoidance of tolerance by use of informed
      dosing schedules, cold water extraction of codeine, and using codeine as an
      alternative to stronger opioids. Oral and rectal routes were favoured, with
      awareness on forums of the harms of intravenous and subcutaneous injection. 250
      mg was recommended to optimise recreational outcomes. Forum users describe
      potentiating practices and using over-the-counter medications to improve
      intoxication experiences and reduce unpleasant side effects. Dissociative
      effects, ability to ignore physical and emotional pain, codeine induced
      synaesthesia and altered states of consciousness were described. Overdose was
      characterised by anaesthesia, severe chest and stomach pain, respiratory
      depression, panic and fear of death. CONCLUSION: Efforts to ensure legitimate
      codeine use for pain and reduction of aberrant behaviours centre on evidence
      based screening, risk minimisation, prescription monitoring and specific
      treatment protocols. This study shows that internet drug forums drive communal
      know-how and indigenous harm reduction strategies, and warrant consideration as
      viable public health mechanisms for informing users.

PMID- 25052241
TI  - Latent TGF-beta1 is compartmentalized between blood and seminal plasma of HIV
      positive men and its activation in semen is negatively correlated with viral load
      and immune activation.
AB  - PROBLEM: Semen is the primary medium for sexual transmission of HIV-1 and
      contains high concentrations of TGF-beta1, but its role in regulating HIV
      mediated immune activation is unclear. METHOD OF STUDY: TGF-beta1 and sCD14 were
      compared in blood plasma (BP) and seminal plasma (SP) from HIV-uninfected and
      infected, antiretroviral therapy (ART)-naive and ART-treated men and in THP-1
      cells following exposure to HIV-1. The relationship between TGF-beta1 and sCD14
      was determined by Spearman correlation. RESULTS: Active and latent forms of TGF
      beta1 were compartmentalized between BP and SP. Highest active TGF-beta1 levels
      were present in SP of ART-naive chronic-infected men and decreased following ART
      treatment. Latent TGF-beta1 was upregulated in BP following HIV infection, and
      highest levels were observed in BP of acute-infected men. Similar expression
      trends were observed between latent TGF-beta1 and sCD14 in BP. A significant
      negative correlation was observed between active TGF-beta1, sCD14, and semen
      viral load in ART-naive men. CONCLUSION: TGF-beta1 is compartmentalized between
      blood and semen, possibly co-expressed with sCD14 by activated
      monocytes/macrophages in BP as a result of HIV infection. Conversion of latent
      TGF-beta1 into its active form could contribute to regulation of viral load and
      immune activation in the male genital tract, but depends on the stage of
      infection.

PMID- 25052242
TI  - Exploratory space-time analysis of dengue incidence in Trinidad: a retrospective
      study using travel hubs as dispersal points, 1998-2004.
AB  - BACKGROUND: Dengue is an acute arboviral disease responsible for most of the
      illness and death in tropical and subtropical regions. Over the last 25 years
      there has been increase epidemic activity of the disease in the Caribbean, with
      the co-circulation of multiple serotypes. An understanding of the space and time
      dynamics of dengue could provide health agencies with important clues for
      reducing its impact. METHODS: Dengue Haemorrhagic Fever (DHF) cases observed for
      the period 1998-2004 were georeferenced using Geographic Information System
      software. Spatial clustering was calculated for individual years and for the
      entire study period using the Nearest Neighbor Index. Space and time interaction
      between DHF cases was determined using the Knox Test while the Nearest Neighbor
      Hierarchical method was used to extract DHF hot spots. All space and time
      distances calculated were validated using the Pearson r significance test.
      RESULTS: Results shows that (1) a decrease in mean distance between DHF cases
      correlates with activity leading up to an outbreak, (2) a decrease in temporal
      distance between DHF cases leads to increased geographic spread of the disease,
      with an outbreak occurrence about every 2 years, and (3) a general pattern in the
      movement of dengue incidents from more rural to urban settings leading up to an
      outbreak with hotspot areas associated with transportation hubs in Trinidad.
      CONCLUSION: Considering only the spatial dimension of the disease, results
      suggest that DHF cases become more concentrated leading up to an outbreak.
      However, with the additional consideration of time, results suggest that when an
      outbreak occurs incidents occur more rapidly in time leading to a parallel
      increase in the rate of distribution of the disease across space. The results of
      this study can be used by public health officers to help visualize and understand
      the spatial and temporal patterns of dengue, and to prepare warnings for the
      public. Dengue space-time patterns and hotspot detection will provide useful
      information to support public health officers in their efforts to control and
      predict dengue spread over critical hotspots allowing better allocation of
      resources.

PMID- 25052243
TI  - Differential effects of MDMA and methylphenidate on social cognition.
AB  - Social cognition is important in everyday-life social interactions. The social
      cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and
      methylphenidate (both used for neuroenhancement and as party drugs) are largely
      unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40
      mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy
      Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test
      and the Moral Judgment Task in a cross-over study in 30 healthy subjects.
      Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug
      effects were measured. MDMA enhanced emotional empathy for positive emotionally
      charged situations in the MET and tended to reduce the recognition of sad faces
      in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy
      in the Multifaceted Empathy Test or social cognitive inferences in the Movie for
      the Assessment of Social Cognition. MDMA produced subjective 'empathogenic'
      effects, such as drug liking, closeness to others, openness and trust. In
      contrast, methylphenidate lacked such subjective effects and did not alter
      emotional processing, empathy or mental perspective-taking. MDMA but not
      methylphenidate increased the plasma levels of oxytocin and prolactin. None of
      the drugs influenced moral judgment. Effects on emotion recognition and emotional
      empathy were evident at a low dose of MDMA and likely contribute to the
      popularity of the drug. 

PMID- 25052244
TI  - Structural and mechanical characterisation of bridging veins: A review.
AB  - Bridging veins drain the venous blood from the cerebral cortex into the superior
      sagittal sinus (SSS) and doing so they bridge the subdural space. Despite their
      importance in head impact biomechanics, little is known about their properties
      with respect to histology, morphology and mechanical behaviour. Knowledge of
      these characteristics is essential for creating a biofidelic finite element model
      to study the biomechanics of head impact, ultimately leading to the improved
      design of protective devices by setting up tolerance criteria. This paper
      presents a comprehensive review of the state-of-the-art knowledge on bridging
      veins. Tolerance criteria to prevent head injury through impact have been set by
      a number of research groups, either directly through impact experiments or by
      means of finite element (FE) simulations. Current state-of-the-art FE head models
      still lack a biofidelic representation of the bridging veins. To achieve this, a
      thorough insight into their nature and behaviour is required. Therefore, an
      overview of the general morphology and histology is provided here, showing the
      clearly heterogeneous nature of the bridging vein complex, with its three
      different layers and distinct morphological and histological changes at the
      region of outflow into the superior sagittal sinus. Apart from a complex
      morphology, bridging veins also exhibit complex mechanical behaviour, being
      nonlinear, viscoelastic and prone to damage. Existing material models capable of
      capturing these properties, as well as methods for experimental characterisation,
      are discussed. Future work required in bridging vein research is firstly to
      achieve consensus on aspects regarding morphology and histology, especially in
      the outflow cuff segment. Secondly, the advised material models need to be
      populated with realistic parameters through biaxial mechanical experiments
      adapted to the dimensions of the bridging vein samples. Finally, updating the
      existing finite element head models with these parameters will render them truly
      biofidelic, allowing the establishment of accurate tolerance criteria and,
      ultimately, better head protection devices. 

PMID- 25052245
TI  - Chen's U-suture technique for end-to-end invaginated pancreaticojejunostomy
      following pancreaticoduodenectomy.
AB  - BACKGROUND AND PURPOSE: Internationally, postoperative pancreatic fistula (POPF)
      remains a leading cause of morbidity and mortality after pancreaticoduodenectomy
      (PD). In order to reduce the incidence of POPF, a number of technical
      modifications for pancreato-enteric anastomosis after PD have been proposed. In
      1995, we established a new technique with transpancreatic transverse U-sutures
      for end-to-end invaginated pancreaticojejunostomy after a PD, and the preliminary
      results were quite encouraging. This study aims to review a new surgical
      approach, the Chen's U-stitch technique, for end-to-end invaginated
      pancreaticojejunostomy, which involves two to four transpancreatic transverse U
      sutures, and to evaluate the effectiveness of this approach with reducing the
      incidence of POPF formation. METHODS: To evaluate this new approach, during 2002
      2012, a total of 264 patients who received the new Chen's U-stitch technique
      after a PD were included in this study. Postoperative morbidity and mortality,
      including the incidence of POPF, were analyzed. RESULTS: Postoperative morbidity
      was 22.3 % (59/264) and mortality was 0 % (0/264). The POPF rate was 3.4 %
      (9/264) for Grade A, 0.8 % (2/264) for Grade B, and 0 % (0/264) for Grade C.
      CONCLUSIONS: This new surgical technique (Chen's U-stitch), which involves an end
      to-end invaginated pancreaticojejunostomy with two to four transpancreatic
      transverse U-sutures, provides excellent outcomes at reducing the incidence of
      POPF after PD.

PMID- 25052246
TI  - Total skin-sparing mastectomy and immediate breast reconstruction: an evolution
      of technique and assessment of outcomes.
AB  - BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the breast
      and nipple-areolar complex (NAC) skin was developed to improve aesthetic outcomes
      for mastectomy. Over time, indications for TSSM broadened and our technique has
      evolved with a series of systematic improvements. METHODS: We reviewed all cases
      of TSSM with immediate breast reconstruction performed from 2005 to 2012. Patient
      comorbidities, treatment characteristics, postoperative complications, and
      outcomes were obtained prospectively and through medical chart review.
      Locoregional recurrences, distant recurrences, and patient survival were analyzed
      with Kaplan-Meier methods. RESULTS: During this 8-year period, 633 patients (981
      cases) underwent TSSM with median follow-up time of 29 (interquartile range 14
      54) months. Immediate breast reconstruction was performed with tissue expander
      placement (89 %), pedicle TRAM (5 %), free flap (5 %), permanent implant (0.3 %),
      or latissimus flap (0.2 %). The incidences of postoperative complications
      decreased significantly over time. In 2012, these were down to 3.5 % for
      superficial nipple necrosis, 1.0 % for complete nipple necrosis, 3.0 % for minor
      skin flap necrosis, 4.4 % for major skin flap necrosis, 13.3 % for infections
      requiring oral antibiotics, 9.9 % for infections requiring intravenous
      antibiotics, 3.4 % for infections requiring operative intervention, and 8.5 % for
      expander/implant. Overall 5-year cumulative incidences of recurrence were 3.0 %
      (locoregional) and 4.2 % (distant), and there were no recurrences in the NAC
      skin. CONCLUSIONS: Systematic changes in our technique of TSSM and immediate
      breast reconstruction have decreased postoperative complications over time.
      Oncologic outcomes of locoregional and distal recurrences remain similar to skin
      sparing mastectomy techniques.

PMID- 25052247
TI  - Impact of availability of immediate breast reconstruction on bilateral mastectomy
      rates for breast cancer across the United States: data from the nationwide
      inpatient sample.
AB  - BACKGROUND: Availability of immediate breast reconstruction (IBR) varies among
      institutions, yet the impact of IBR availability on the rates of bilateral
      mastectomy (BM) versus unilateral mastectomy (UM) for breast cancer is unknown.
      METHODS: From the 2002 to 2010 Nationwide Inpatient Sample, we identified women
      with breast cancer undergoing UM or BM with and without IBR using ICD-9 codes.
      Hospitals were classified as performing IBR if at least one hospitalization
      included both mastectomy and reconstruction and then by IBR volume. Statistical
      comparisons utilized Chi square tests, tests for trend, and multivariable
      logistic regression. RESULTS: We identified 130,420 women undergoing UM (76.9 %)
      or BM (23.1 %) for breast cancer. Of 6,579 hospitals, 3,358 (51.0 %) performed no
      IBRs, while in the remaining 3,221 hospitals, 1 to 638 IBRs were performed per
      year. Large, teaching, urban, and Northeastern hospitals were more likely to have
      higher IBR volumes. BM rates were significantly higher in patients treated at
      those hospitals with higher IBR volumes, from 33.1 % at hospitals performing >=24
      IBRs per year to 9.0 % at hospitals without IBR (p < 0.001). Upon adjusted
      analysis, patients who elected BM were more likely to be seen at hospitals
      performing >=24 IBRs per year (odds ratio 1.69 vs. UM, p < 0.001). CONCLUSIONS:
      In this analysis of national data, BM rates were higher in hospitals where IBR
      was available, suggesting a significant influence of institutional factors on
      treatment options for breast cancer patients. Efforts are needed to ensure
      patients have access to IBR when desired and to better understand the reasons for
      hospital variation in BM rates.

PMID- 25052248
TI  - In vitro interactions of calcineurin inhibitors with conventional antifungal
      agents against the yeast form of Penicillium marneffei.
AB  - Penicillium marneffei can cause a life-threatening disseminated mycosis in
      immunocompromised hosts. However, therapeutic strategies for the treatment of
      this infectious disease are limited. Reports of other fungi suggest that
      calcineurin inhibitors interact with antifungal agents to improve the treatment
      outcomes. Here, we evaluated the in vitro interaction of the calcineurin
      inhibitors cyclosporine A and tacrolimus (FK506) combined with conventional
      antifungal agents against the pathogenic yeast form of P. marneffei. We
      demonstrate that the combination of cyclosporine A with amphotericin B,
      itraconazole, or fluconazole was synergistic for 85, 65, and 30 % of P. marneffei
      strains, respectively. In contrast, no synergism was observed in all the
      combinations containing tacrolimus. Furthermore, antagonism was not observed for
      any combination. In conclusion, the therapeutic potential of a combinatory
      approach using the calcineurin inhibitor cyclosporine A with conventional
      antifungal drugs may lead to improved treatment regimens for P. marneffei
      infections. We propose that mechanism of action studies with cyclosporine A and
      antifungal agents is needed.

PMID- 25052249
TI  - Multimedia in biochemistry and molecular biology education. Websites of note.

PMID- 25052250
TI  - Lab on upconversion nanoparticles: optical properties and applications
      engineering via designed nanostructure.
AB  - Over the past decade, high-quality lanthanide doped upconverting nanoparticles
      (UCNPs) have been successfully synthesized with the rapid development of
      nanotechnology. Due to the unique electron configuration of lanthanide ions,
      there are rich energy level structures in the near-infrared, visible and
      ultraviolet spectral range. However, for UCNPs, only a limited number of
      efficient upconversion excitation and emission have been generated due to the
      limited number of sensitizer (Yb(3+)) and activator (Tm(3+), Er(3+), and Ho(3+))
      ions, and the application is mainly focused on the bio-imaging by using the
      upconversion luminescence of UCNPs. Recently, more and more researchers have
      started to focus on tuning of upconversion optical properties and developing of
      multi-functional UCNPs by using the combination of sub-lattice mediated energy
      migration, core@shell structural engineering and UCNPs based nanocomposites which
      greatly expands the range of applications for lanthanide-doped UCNPs. Therefore,
      a "nanolab" can be created on UCNPs, where the property modulation can be
      realized via the designed host-dopants combinations, core@shell nanostructure,
      energy exchange with "alien species" (organic dyes, quantum dots, etc.), and so
      on. In this paper, we provide a comprehensive survey of the latest advances made
      in developing lanthanide-doped UCNPs, which include excitation and emission
      energy levels guided designing of the UCNP nanostructure, the synthesis
      techniques to fabricate the nanostructure with optimum energy level structure and
      optical properties, the fabrication of UCNPs-based nanocomposites to extend the
      applications by introducing the additional functional components, or integrating
      the functional moiety into one nanocomposite. 

PMID- 25052251
TI  - Hematologic differences between Dachshunds and mixed breed dogs.
AB  - BACKGROUND: Healthy Dachshunds, like Greyhounds, are reported to have a higher
      HCT than other dog breeds; however, there appears to be no objective information
      to support this observation. OBJECTIVE: The purpose of this study was to
      determine whether RBC counts, indices, and total and differential WBC counts
      differ between Dachshunds and mixed breed dogs. METHODS: In this retrospective
      study, CBC data and total solids were compared between 61 healthy Dachshunds and
      60 mixed breed dogs that were presented for health check, dental prophylaxis, or
      neutering to a university and a private clinic. RESULTS: Dachshunds had higher
      mean PCV (52% vs 50%; P = .047), mean HCT (52% vs 48%; P = .0003), mean RBC count
      (7.7 * 10(6) /MUL vs 7.1 * 10(6) /MUL; P = .0004), and mean HGB concentration
      (18.2 g/dL vs 16.8 g/dL; P = .0003) than mixed breed dogs. There were slight
      differences in HCT and HGB concentration between clinics (P < .05). There was no
      evidence of a difference in MCV, MCHC, and total solids between breeds (P > .5).
      More Dachshunds than mixed breed dogs had RBC variables above the reference
      interval: 29% vs 2% for HCT (P = .001); 40% vs 7% for HGB concentration (P =
      .0006); and 26% vs 5% for RBC count (P = .01). There were statistically
      significant but clinically unimportant differences in differential WBC counts.
      CONCLUSIONS: Compared with mixed breed dogs, Dachshunds have higher PCV, HCT, RBC
      count, and HGB concentration. Veterinarians should consider these differences
      when interpreting CBCs.

PMID- 25052252
TI  - What can we learn about visual attention to multiple words from the word-word
      interference task?
AB  - In this work, we develop an empirically driven model of visual attention to
      multiple words using the word-word interference (WWI) task. In this task, two
      words are simultaneously presented visually: a to-be-ignored distractor word at
      fixation, and a to-be-read-aloud target word above or below the distractor word.
      Experiment 1 showed that low-frequency distractor words interfere more than high
      frequency distractor words. Experiment 2 showed that distractor frequency (high
      vs. low) and target frequency (high vs. low) exert additive effects. Experiment 3
      showed that the effect of the case status of the target (same vs. AlTeRnAtEd)
      interacts with the type of distractor (word vs. string of # marks). Experiment 4
      showed that targets are responded to faster in the presence of semantically
      related distractors than in presence of unrelated distractors. Our model of
      visual attention to multiple words borrows two principles governing processing
      dynamics from the dual-route cascaded model of reading: cascaded interactive
      activation and lateral inhibition. At the core of the model are three mechanisms
      aimed at dealing with the distinctive feature of the WWI task, which is that two
      words are presented simultaneously. These mechanisms are identification,
      tokenization, and deactivation. 

PMID- 25052253
TI  - An update of the goat genome assembly using dense radiation hybrid maps allows
      detailed analysis of evolutionary rearrangements in Bovidae.
AB  - BACKGROUND: The domestic goat (Capra hircus), an important livestock species,
      belongs to a clade of Ruminantia, Bovidae, together with cattle, buffalo and
      sheep. The history of genome evolution and chromosomal rearrangements on a small
      scale in ruminants remain speculative. Recently completed goat genome sequence
      was released but is still in a draft stage. The draft sequence used a variety of
      assembly packages, as well as a radiation hybrid (RH) map of chromosome 1 as part
      of its validation. RESULTS: Using an improved RH mapping pipeline, whole-genome
      dense maps of 45,953 SNP markers were constructed with statistical confidence
      measures and the saturated maps provided a fine map resolution of approximate 65
      kb. Linking RH maps to the goat sequences showed that the assemblies of
      scaffolds/super-scaffolds were globally accurate. However, we observed certain
      flaws linked to the process of anchoring chromosome using conserved synteny with
      cattle. Chromosome assignments, long-range order, and orientation of the
      scaffolds were reassessed in an updated genome sequence version. We also present
      new results exploiting the updated goat genome sequence to understand genomic
      rearrangements and chromosome evolution between mammals during species
      radiations. The sequence architecture of rearrangement sites between the goat and
      cattle genomes presented abundant segmental duplication on regions of goat
      chromosome 9 and 14, as well as new insertions in homologous cattle genome
      regions. This complex interplay between duplicated sequences and Robertsonian
      translocations highlights the rearrangement mechanism of centromeric nonallelic
      homologous recombination (NAHR) in mammals. We observed that species-specific
      shifts in ANKRD26 gene duplication are coincident with breakpoint reuse in
      divergent lineages and this gene family may play a role in chromosome
      stabilization in chromosome evolution. CONCLUSIONS: We generated dense maps of
      the complete whole goat genome. The chromosomal maps allowed us to anchor and
      orientate assembled genome scaffolds along the chromosomes, annotate chromosome
      rearrangements and thereby get a better understanding of the genome evolution of
      ruminants and other mammals.

PMID- 25052254
TI  - Predicting remission of diabetes after RYGB surgery following intensive
      management to optimize preoperative glucose control.
AB  - BACKGROUND: The purpose of the study is to investigate the association of
      preoperative glucose optimization prior to a Roux-en-Y gastric bypass (RYGB) and
      diabetes remission. METHODS: The study is a retrospective review of 245 patients
      with a history of diabetes type II and a RYGB from 2008 to 2012 at UMass Memorial
      Hospital. RESULTS: Patients that benefited from glucose optimization prior to
      RYGB were more likely to achieve diabetes remission 1 year after surgery. The
      preoperative glucose optimization intervention demonstrated that when patients
      decreased their HbA1c prior to surgery by 1 %, these individuals were 68 % more
      likely to remit (p = 0.015). Duration of diabetes (p = 0.005) and insulin use (p
      < 0.001) were also significant predictors of remission, whereas age, race, and
      gender were not. CONCLUSIONS: Our study results indicate that a greater degree of
      glycemic improvement in response to presurgical medical intervention is
      associated with higher rates of diabetes remission post-operatively among obese
      adults with diabetes type II. Conversely, the lack of favorable glycemic response
      to intensification of medical management predicts a poor glycemic response to
      bariatric surgery. Further research is needed to determine if this difference is
      due to physiological factors or is simply an indicator of patient behavior.

PMID- 25052255
TI  - Isolated intestinal neuronal dysplasia Type B (IND-B) in Japan: results from a
      nationwide survey.
AB  - PURPOSE: Intestinal neuronal dysplasia Type B (IND-B) has been proposed to be an
      allied disorder of Hirschsprung's disease (ADHD). The original histological
      criteria included hyperganglionosis, giant ganglia, ectopic ganglion cells and an
      increased AChE activity in the lamina propria. The criteria for IND-B have been
      gradually revised. The present diagnostic criteria are [1] more than 20 % of the
      submucosal ganglia contain nine or more ganglion cells and [2] the patient is
      older than 1 year. To clarify the current status of IND-B in Japan, a nationwide
      retrospective cohort study was performed. METHODS: Questionnaires were sent to
      161 major institutes of pediatric surgery and gastroenterology in Japan. RESULTS:
      A total of 355 cases of ADHD were collected, including 18 cases of IND-B (5 %).
      Based on original criteria, 13 out of 18 cases were diagnosed as IND-B. However,
      only four cases met the current criteria. Three of the four patients (75 %)
      required pull-through operation. All of the patients exhibited giant ganglia and
      ganglioneuromatosis-like hyperplasia of the myenteric plexus. CONCLUSIONS: IND-B
      cases matching the current criteria are thought to be quite rare and they are
      associated with marked hyperplasia of the myenteric plexus. "True" IND-B is a
      rare and intractable disease.

PMID- 25052257
TI  - Is the measurement of serum cytokeratin-18 useful for diagnosis or screening non
      alcoholic steatohepatitis?

PMID- 25052256
TI  - Thoracoscopic versus open repair of esophageal atresia with tracheoesophageal
      fistula at a single institution.
AB  - PURPOSE: The potential benefits of thoracoscopic repair (TR) of esophageal
      atresia and tracheoesophageal fistula (EA/TEF) in newborns are still unclear. Our
      aim was to define the criteria, perioperative outcome after undergoing TR versus
      open repair (OR) for EA/TEF. PATIENTS AND METHODS: A retrospective chart review
      was conducted of 36 consecutive neonates who underwent EA/TEF repair between 2001
      and 2012 in Shizuoka Children's Hospital. Patients in this study were birth
      weight >2,000 g, and did not have severe cardiac malformations or chromosomal
      aberrations. Of the 26 newborns who met the selection criteria, 11 patients
      underwent attempts at TR compared to 15 patients who underwent OR. All cases were
      followed 1 year after operation at least. RESULTS: All 11 TR were successfully
      completed. There were no significant differences between intra- and perioperative
      complications in the two groups. Intraoperative EtCO2 and arterial blood gases
      were not significantly different between the two groups. We did not found eating
      disorder, respiratory disorder, and failure of growth in all cases. CONCLUSION:
      In our study, the thoracoscopic approach appeared to be favorable and safe for
      EA/TEF repair in carefully selected patients.

PMID- 25052258
TI  - Detection of the secondary, low-affinity beta1 -adrenoceptor site in living cells
      using the fluorescent CGP 12177 derivative BODIPY-TMR-CGP.
AB  - BACKGROUND AND PURPOSE: CGP 12177 not only inhibits agonist effects mediated
      through the catecholamine site of the beta1 -adrenoceptor with high affinity, but
      also exhibits agonist effects of its own at higher concentrations through a
      secondary, low-affinity beta1 -adrenoceptor site or conformation. beta-blocker
      affinities for this 'CGP 12177' site of the human beta1 -adrenoceptor have thus
      far only been characterized in functional studies. Here, we used the fluorescent
      CGP 12177 analogue BODIPY-TMR-CGP to directly investigate receptor-ligand
      interactions at the secondary binding site of the beta1 -adrenoceptor.
      EXPERIMENTAL APPROACH: The human beta1 -adrenoceptor was stably expressed in CHO
      cells containing a cAMP response element (CRE)-secreted placental alkaline
      phosphatase (SPAP) reporter gene construct. Functional responses of BODIPY-TMR
      CGP were determined in the CRE-SPAP reporter gene assay, and manual and automated
      confocal microscopy platforms used to investigate the binding properties of
      BODIPY-TMR-CGP. KEY RESULTS: BODIPY-TMR-CGP displayed a pharmacological profile
      similar to that of CGP 12177, retaining agonist activity at the secondary beta1 
      adrenoceptor site. In confocal microscopy studies, specific BODIPY-TMR-CGP
      binding allowed clear visualization of beta1 -adrenoceptors in live cells. Using
      a wider concentration range of labelled ligand in a high-content fluorescence
      based binding assay than is possible in radioligand binding assays, two-site
      inhibition binding curves of beta-adrenoceptor antagonists were revealed in CHO
      cells expressing the human beta1 -adrenoceptor, but not the beta2 -adrenoceptor.
      CONCLUSIONS AND IMPLICATIONS: The fluorescent CGP 12177 analogue allowed the
      detection of the beta1 -adrenoceptor secondary site in both functional and
      binding studies. This suggests that BODIPY-TMR-CGP presents an important and
      novel fluorescent tool to investigate the nature of the secondary beta1 
      adrenoceptor site.

PMID- 25052259
TI  - Renoprotective effects of gamma-aminobutyric acid on cisplatin-induced acute
      renal injury in rats.
AB  - To investigate the effect of gamma-aminobutyric acid (GABA) on acute renal injury
      (ARI), we used here a rat model of acute tubular necrosis induced by the
      anticancer drug cisplatin (CP). GABA was given orally (100 or 500 mg/kg/day for
      ten consecutive days), and on the 6th day, some of the treated rats were also
      injected intraperitoneally with either saline or CP (6 mg/kg). Four days after CP
      treatment, urine was collected from all rats, which were then anaesthetized for
      blood pressure and renal blood flow monitoring. This was followed by intravenous
      injection of norepinephrine for the assessment of renal vasoconstrictor
      responses. Thereafter, blood and kidneys were collected for measurement of
      several functional, biochemical and structural parameters. GABA treatment (at 500
      but not 100 mg/kg) significantly mitigated all the measured physiological and
      biochemical indices. Sections from saline- and GABA-treated rats showed
      apparently normal proximal tubules. However, kidneys of CP-treated rats had a
      moderate degree of necrosis. This was markedly lessened when CP was given
      simultaneously with GABA (500 mg/kg). The concentration of platinum in the
      cortical tissues was not significantly altered by GABA treatment. The results
      suggested that GABA can ameliorate CP nephrotoxicity in rats. Pending further
      pharmacological and toxicological studies, GABA may be considered a potentially
      useful nephroprotective agent in CP-induced ARI. 

PMID- 25052260
TI  - Enhanced protection of pathogenic Escherichia coli ingested by a soil nematode
      Caenorhabditis elegans against sanitizer treatments.
AB  - We employed Caenorhabditis elegans as a model to study the effectiveness of
      sanitizers in killing pathogenic Escherichia coli strains ingested by free-living
      nematodes. Adult worms that had fed on six pathogenic E. coli strains (highly
      persistent in the nematode intestine) were treated with three chemical solutions.
      In planktonic cells, none of the H2O2 and acetic acid treatments influenced the
      survival of the pathogenic E. coli strains, whereas sodium hypochlorite
      critically decreased the viability of the strains. Importantly, the survival of
      the E. coli strains was dramatically increased by persistence in the C. elegans
      gut under 0.1% sodium hypochlorite, and several strains could survive at a
      concentration of 0.5%. In addition, all pathogenic E. coli strains in the C.
      elegans gut survived on the lettuce for 5 days even though they were washed with
      0.1% sodium hypochlorite. Taken together, our results indicate that pathogenic E.
      coli ingested by C. elegans may be protected against washing treatment with
      commercial sanitizers on raw food materials.

PMID- 25052261
TI  - The economic burden of psoriasis: a systematic literature review.
AB  - Costs associated with psoriasis present a considerable economic burden. A
      previously published review was lacking comprehensive data on biologics.
      Therefore, a systematic literature review was performed to gain a comprehensive
      understanding of the economic burden of psoriasis throughout the world. Studies
      published in the English language between January 2001 and May 2013 reporting the
      direct and indirect economic burden of psoriasis were identified from PubMed and
      conference proceedings. Thirty-five studies from 11 countries met the inclusion
      criteria. In 2004, the annual total cost (direct and indirect) in the USA alone
      was approximately US$1.40 billion. Among the European countries, the most recent
      studies reported an annual total cost per patient of ?11,928 in Sweden, ?8372 in
      Italy, ?2866-6707 in Germany and CDN$7999 in Canada, based on treatment type.
      Costs associated with psoriasis are high in many countries, indicating a
      continued need for treatments that offer good value for money. 

PMID- 25052263
TI  - Acclimatization to long-term hypoxia: gene expression in ovine carotid arteries.
AB  - Exposure to acute high-altitude hypoxia is associated with an increase in
      cerebral blood flow (CBF) as a consequence of low arterial O2 tension. However,
      in response to high altitude acclimatization, CBF returns to levels similar to
      those at sea level, and tissue blood flow is maintained by an increase in
      angiogenesis. Of consequence, dysregulation of the acclimatization responses and
      CBF can result in acute mountain sickness, acute cerebral and/or pulmonary edema.
      To elucidate the signal transduction pathways involved in successful
      acclimatization to high altitude, in ovine carotid arteries, we tested the
      hypothesis that high altitude-associated long-term hypoxia results in changes in
      gene expression of critical signaling pathways. We acclimatized nonpregnant adult
      sheep to 3,801 m altitude for ~110 days and conducted oligonucleotide microarray
      experiments on carotid arteries. Of a total of 116 regulated genes, 58 genes were
      significantly upregulated and 58 genes were significantly downregulated (each >2
      fold, P < 0.05). Major upregulated genes included suprabasin and myelin basic
      protein, whereas downregulated genes included BAG2. Several of these genes are
      known to activate the ERK canonical signal transduction pathway and the process
      of angiogenesis. We conclude that among other changes, the altered signal
      transduction molecules involved in high-altitude acclimatization are associated
      ERK activation and angiogenesis. 

PMID- 25052264
TI  - [Gene geography of Chile: regional distribution of American, European and African
      genetic contributions].
AB  - BACKGROUND: The geographical distribution of genes plays a key role in genetic
      epidemiology. The Chilean population has three major stem groups (Native
      American, European and African). AIM: To estimate the regional rate of American,
      European and African admixture of the Chilean population. SUBJECTS AND METHODS:
      Forty single nucleotide polymorphisms (SNP's) which exhibit substantially
      different frequencies between Amerindian populations (ancestry-informative
      markers or AIM's), were genotyped in a sample of 923 Chilean participants to
      estimate individual genetic ancestry. RESULTS: The American, European and African
      individual average admixture estimates for the 15 Chilean Regions were relatively
      homogeneous and not statistically different. However, higher American components
      were found in northern and southern Chile and higher European components were
      found in central Chile. A negative correlation between African admixture and
      latitude was observed. On the average, American and European genetic
      contributions were similar and significantly higher than the African
      contribution. Weighted mean American, European and African genetic contributions
      of 44.34% +/- 3 9%, 51.85% +/- 5.44% and 3.81% +/- 0.45%, were estimated. Fifty
      two percent of subjects harbor African genes. Individuals with Aymara and Mapuche
      surnames have an American admixture of 58.64% and 68.33%, respectively.
      CONCLUSIONS: Half of the Chilean population harbors African genes. Participants
      with Aymara and Mapuche surnames had a higher American genetic contribution than
      the general Chilean population. These results confirm the usefulness of surnames
      as a first approximation to determine genetic ancestry.

PMID- 25052265
TI  - [Association between genetic polymorphisms of interleukin 6 (IL6), IL6R and IL18
      with metabolic syndrome in obese Chilean children].
AB  - BACKGROUND: Metabolic Syndrome (MS) is highly prevalent among obese children and
      adolescents and is considered a predictor for the development of type 2 diabetes
      mellitus and cardiovascular disease. Obesity is associated with an increase in
      circulating levels of interleukins 6 (IL6) and 18 (IL18), which in turn would
      depend on polymorphisms of IL6, IL6R and IL18 genes. AIM: To evaluate the
      association between genetic polymorphisms of IL6 (rs1800795, rs1800796 and
      rs1800797), IL6R (rs2228145) and IL18 (rs360719, rs187238 and rs204355) and MS
      and/or its components in a sample of Chilean obese children. PATIENTS AND
      METHODS: These polymorphisms were genotyped in 259 obese children aged 10 +/- 2
      years with a body mass index of 26.1 +/- 4.1 kg/m2. Sixty eight had metabolic
      syndrome (26.3%). The association of their alleles, genotypes and haplotypes with
      the MS and its components was assessed. RESULTS: IL6, IL6R and IL18 variants
      showed no association with SM nor with any of the phenotypes that compose it.
      However, IL18 haplotypes (rs360719-rs187238-rs204355) TCT and CGT were associated
      with triglycerides <= 110 mg/dL and HDL < 40 mg/dL, respectively. CONCLUSIONS:
      IL6 and IL6R variants are not associated with MS or with any of its phenotypes.
      Although an association between IL18 haplotypes and certain MS component has been
      detected herein, it is necessary to replicate our findings in independent studies
      due to the low frequency of these allele combinations detected in our sample.

PMID- 25052266
TI  - [Immediate complications following flexible bronchoscopy: retrospective analysis
      of 1079 procedures].
AB  - BACKGROUND: Flexible bronchoscopy is a useful diagnostic tool with a relative low
      rate of complications. AIM: To analyze post procedure risk of complications after
      flexible bronchoscopy with transbronchial or bronchial biopsy. MATERIAL AND
      METHODS: The electronic database of a bronchoscopy unit at a general Hospital was
      analyzed. All procedures performed between 2009 and 2011 were reviewed and
      complications recorded. The primary outcome measure was the risk for
      complications defined as the percentage of procedures complicated by hemorrhage,
      pneumothorax, desaturation < 80% and other complications. We used a logistic
      regression model to explore the association between each procedure characteristic
      and complication. RESULTS: One thousand seventy nine procedures were included in
      the analysis. Eight percent had complications. Among these, the frequency of
      hemorrhage was 5.9% and pneumothorax was 0.3%. Factors associated with
      complications were exclusive use of topical anesthesia with an odds ratio (OR) of
      1.72 (confidence intervals (CI): 1.04-2.86), regular or bad intolerance to the
      procedure with an OR 4.70 (CI: 3.00-7.38) and performing biopsies of the upper
      lobes with an OR of 1.76 (CI: 1.04-2.97). CONCLUSIONS: Exclusive use of topical
      anesthesia, performing biopsies of the upper lobes and procedure tolerance were
      risk factors associated with complications following bronchoscopic biopsies.

PMID- 25052267
TI  - [Trends in suicide mortality in Chile from 1998 to 2011].
AB  - BACKGROUND: Suicide is an important public health problem accounting for an
      important proportion of deaths in Chile. AIM: To describe trends in suicide
      mortality in Chile between 1998 and 2011, by year, region, sex and age. MATERIAL
      AND METHODS: A population survey study was conducted using suicide mortality data
      of Chile from 1998 to 2011, provided by the statistics department of the Ministry
      of Health, Coroners' offices and the Pan American Health Organization (PAHO/WHO).
      Age-adjusted suicide mortality rates were calculated per 100,000 habitants.
      Variables analyzed included year, age, sex, etiology and geographical
      distribution. An analysis of the average annual variation (AAV) was performed and
      the logarithm of the age-adjusted rates by year and region was fitted by applying
      linear regression models. Relative risks (RR) by sex, geographical distribution
      and age were also calculated. RESULTS: The mean suicide rate in Chile, was 12.11
      per 100.000 in the period 2000-2011. The rates were higher in men, with a higher
      AAV in women and a relative risk for men was 5.14 higher than in women. The rates
      were higher in the southern regions of the country. Atacama had the highest AAV.
      By age, the rates are consistently higher in subjects aged 40 to 59 years until
      2006, when this pattern started to change. Between 2006 and 2009, subjects aged
      25-39 years had the highest rates. Subjects aged 0 to 14 years, exhibit the
      highest AAV. CONCLUSIONS: The distribution of suicide rates by sex in Chile is
      similar to other countries, but it is different by age. The age range with the
      highest suicide rates changed over time.

PMID- 25052268
TI  - [Detection of HTLV-1 DNA in biopsies of Chilean patients with cutaneous T-cell
      lymphoma].
AB  - BACKGROUND: Human T-lymphotropic virus-1 (HTLV-1) infection has been associated
      with the pathogenesis of cutaneous T cell lymphomas (CTCL). AIM: To search for
      HTLV-1 DNA in skin biopsies of patients with CTCL. MATERIAL AND METHODS: A
      retrospective study was conducted using 25 biopsies of patients with CTCL. DNA
      was extracted from lymphoid tissue by microdissection. A nested PCR was conducted
      to detect HTLV-1 genome using primers for the tax region. As negative controls,
      four cases of superficial perivascular dermatitis were chosen. As positive
      controls, five cases of T-cell leukemia/lymphoma (ATCL) were studied. RESULTS: A
      positive reaction was found in 3 of 25 cases. These biopsies corresponded to a
      case of Mycosis Fungoides, a case of CD30 (-) T-cell lymphoma and a case of
      lymphomatoid papulosis. Search was negative in the four cases of superficial
      perivascular dermatitis and positive in four cases of adult T-cell
      leukemia/lymphoma (ATCL). CONCLUSIONS: HTLV-1 DNA search in tissues is a useful
      tool recommended to study T-cell lymphomas. HTLV-1 infection only occurs in
      sporadic cases but may contribute to tumor aggressiveness and prognosis.

PMID- 25052269
TI  - [Development of an algorithm to predict the incidence of major depression among
      primary care consultants].
AB  - BACKGROUND: The reduction of major depression incidence is a public health
      challenge. AIM: To develop an algorithm to estimate the risk of occurrence of
      major depression in patients attending primary health centers (PHC). MATERIAL AND
      METHODS: Prospective cohort study of a random sample of 2832 patients attending
      PHC centers in Concepcion, Chile, with evaluations at baseline, six and twelve
      months. Thirty nine known risk factors for depression were measured to build a
      model, using a logistic regression. The algorithm was developed in 2,133 patients
      not depressed at baseline and compared with risk algorithms developed in a sample
      of 5,216 European primary care attenders. The main outcome was the incidence of
      major depression in the follow-up period. RESULTS: The cumulative incidence of
      depression during the 12 months follow up in Chile was 12%. Eight variables were
      identified. Four corresponded to the patient (gender, age, depression background
      and educational level) and four to patients' current situation (physical and
      mental health, satisfaction with their situation at home and satisfaction with
      the relationship with their partner). The C-Index, used to assess the
      discriminating power of the final model, was 0.746 (95% confidence intervals (CI
      = 0,707-0,785), slightly lower than the equation obtained in European (0.790 95%
      CI = 0.767-0.813) and Spanish attenders (0.82; 95% CI = 0.79-0.84). CONCLUSIONS:
      Four of the factors identified in the risk algorithm are not modifiable. The
      other two factors are directly associated with the primary support network
      (family and partner). This risk algorithm for the incidence of major depression
      provides a tool that can guide efforts towards design, implementation and
      evaluation of effectiveness of interventions to prevent major depression.

PMID- 25052270
TI  - [Diagnostic yield of fine-needle aspiration cytology for the detection of thyroid
      cancer in pediatric patients].
AB  - BACKGROUND: Despite the low frequency of thyroid nodules (TN) in children, one of
      every four is malignant. Fine-needle aspiration cytology (FNAC) has a high
      accuracy detecting thyroid cancer. AIM: To evaluate the performance of FNAC in TN
      in Chilean children to detect thyroid cancer. PATIENTS AND METHODS: The
      pathological reports of 77 thyroidectomies and 103 FNAC carried out in patients
      aged less than 18 years, between 2002 and 2013 were reviewed. In 36 patients aged
      15 +/- 2 years (77% women), both the reports of the thyroidectomy and FNAC were
      available. The cytological specimens were reclassified based on Bethesda 2010.
      The histology was classified as benign (nodular hyperplasia and follicular
      adenoma, n = 18), or malignant (papillary, follicular and medullar carcinoma, n =
      18). The concordance of the cytology with the final biopsy report was calculated.
      RESULTS: FNAC classified 13 specimens as definitively benign and 13 as
      definitively malignant. Among these, these concordances with the pathological
      study of the biopsy was 100%. Of six cytology tests considered "suspicious for
      follicular neoplasm" by FNAC, four were benign (67%), and two malignant (33%). Of
      four cytology tests considered "suggestive of carcinoma" by FNAC, one was benign
      (25%), and three malignant (75%). CONCLUSIONS: Among the studied children, there
      was a good concordance between FNAC and surgical biopsies. Therefore a FNAC
      should be carried out when malignancy is suspected in pediatric patients with a
      TN.

PMID- 25052271
TI  - [Impact beyond the objectives: a qualitative study of a faculty development
      program in medical education].
AB  - BACKGROUND: In medical education there has been increasing emphasis on faculty
      development programs aimed at the professionalization of teaching and increasing
      students' learning. However, these programs have been shown to have an impact
      beyond improvement in teaching skills. The medical school of the Pontificia
      Universidad Catolica de Chile (EMUC) has been running a faculty development
      program (DEM) since 2000. AIM: To explore the perception of graduates on the
      effects of having participated in DEM on their development as teachers and
      clinicians. MATERIAL AND METHODS: Using an exploratory, descriptive and
      qualitative design, the 79 teachers who graduated from DEM from 2004-2008 were
      sent a questionnaire containing three open questions. Their answers were analyzed
      using the Constant Comparative Method of Qualitative Analysis of Glaser and
      Strauss by four researchers. RESULTS: Faculty development, becoming a better
      clinician, personal development, appreciation of the value of teaching and
      strengthening of the academic community were the five categories that emerged
      from the answers. Graduates felt that, besides learning new educational skills,
      they changed their attitude towards teaching. DEM was perceived as facilitating
      self-awareness and reflection about the graduates' role as doctors and teachers.
      The graduates also valued meeting other faculty. CONCLUSIONS: Faculty development
      programs can have an impact far beyond the learning objectives. The planning and
      design of programs contributes to their wider impact. This should be taken into
      consideration in the design, planning, and evaluation of faculty development
      programs. Care should be taken to protect time for participation, reflection and
      for interaction with other academics.

PMID- 25052272
TI  - [Acute aortic syndrome. Review and update of the literature].
AB  - Acute aortic syndrome (AAS) is a term that describes interrelated aortic
      emergencies with similar clinical characteristics and challenges. These are
      aortic dissection (AD), intramural hematoma (IH), and penetrating atherosclerotic
      ulcer (PAU). The incidence of AAS is three cases per 100.000 persons per year.
      Diverse genetic disorders and acquired conditions have been related to the
      pathogenesis of this disease. Clinical features of patients with any of the three
      conditions comprising AAS are very similar. A high degree of clinical suspicion
      and imaging studies are necessary for an accurate diagnosis. Prognosis is clearly
      related to underlying diagnosis and appropriate surgical repair, in the case of
      proximal involvement of the aorta. Involvement of distal segments of the aorta
      may require medical or endovascular therapy according to the presence of
      complications. After hospital discharge, patients require lifelong follow-up. 

PMID- 25052273
TI  - [A role for the endocannabinoid system in hepatic steatosis].
AB  - The endocannabinoid system (SEC) is an important modulator of several metabolic
      functions. This system is composed by cannabinoid receptors type 1 and 2 (RCB1
      and RCB2), their endogenous ligands, known as endocannabinoids, and the enzymes
      involved in their synthesis and degradation. A deregulated SEC originates
      metabolic alterations in several tissues, resulting in the typical manifestations
      of the metabolic syndrome. Liver steatosis of different origins constitutes a
      physiopathological condition where an altered hepatic SEC is observed. In this
      condition, there is an increased expression of RCB1 and/or higher endocannabinoid
      levels in different hepatic cells, which may exert an autocrine/paracrine
      hyperstimulation of RCB1/RCB2. Activation of RCB1 stimulate the expression of
      several hepatocyte lipogenic factors, thus leading to increased de novo fatty
      acids synthesis and consequently to an abnormal accumulation of triglycerides.
      The effect of RCB2 activity on hepatic function is still controversial because,
      on one side its stimulation has an interesting protective effect on alcoholic
      liver disease while, on the other, it may enhance the development of hepatic
      steatosis in experimental models of diet-induced obesity. In this review we
      discuss the proposed mechanisms by which SEC is involved in the etiology of
      hepatic steatosis, as well as the therapeutic possibilities involving peripheral
      RCB1/RCB2 antagonism/agonism, for the treatment of this condition. 

PMID- 25052274
TI  - [The relationship between medicine and medical suppliers].
AB  - In the last decades, many voices from academic medicine are questioning the
      relationship between the pharmaceutical industry or other medical suppliers and
      physicians. Conflict of interest has thus become a major issue of concern in
      medicine and is becoming increasingly important for medical journals and clinical
      work. Conflicts of interest may emerge in the daily practice of medicine, in
      medical and pharmacological research, in the process of publication of medical
      journals and in the dissemination of public and private medical information, such
      as conferences, lectures, books, pamphlets, monographs, etc. The credibility of
      physicians has been hampered in recent years by the proliferating connections
      between them and medical suppliers. The public seems to be increasingly skeptical
      of clinical medicine, since corporate actions placing profit over public health
      are usual. Research centers and projects as well as medical journals are
      considered an extension of the marketing arm of pharmaceutical companies. This
      undermines the credibility of medical practice, research work and pharmaceutical
      information, submitted to journals and later included in meta-analysis,
      influencing therapeutic guidelines. In the meantime, while disclosure has become
      standard practice in North America, it is not widely used in Latin-America and
      Europe. If independent researchers are financed by agencies not related to the
      industry, the problems caused by the increasing financial ties between the
      pharmaceutical industry and researchers could be overcome, avoiding conflicts of
      interest. Better disclosure policies and financial tie regulations are also
      urgently needed. 

PMID- 25052275
TI  - [Recommendations of the Ethics Committee of the Chilean Society of Nephrology for
      the management of ethical problems in adult end stage renal disease patients].
AB  - There are different approaches to treat patients with End Stage Renal Disease
      (ESRD): hemodialysis, peritoneal dialysis, renal transplantation and conservative
      medical management. The choice of the best therapy for each patient, needs both
      clinical and ethical skills. The Ethics Committee of the Chilean Society of
      Nephrology has elaborated recommendations to help health workers to deal with the
      ethical and clinical problems related to patients suffering ESRD. Its goal is to
      guide, at a national level, the effective use of minimal standards in the
      treatment and care of patients with ESRD, including appropriate care and
      information for patients, therapy selection, management of difficult cases and
      potential conflicts. 

PMID- 25052276
TI  - [The efficiency of self-regulated learning in the teaching of scientific concepts
      to health sciences students].
AB  - BACKGROUND: In health sciences, the predominant teaching methodology is
      traditional and emphasizes conveying knowledge. Nonetheless, new abilities must
      be taught now. This change shifts the prominence from professor to student and
      incorporates a concept called self-regulated learning, which involves the
      professor as a mediator and incorporates guidelines that facilitate learning
      diverse skills. AIM: To compare the effects of two teaching methodologies on the
      learning of key scientific concepts among health science students. MATERIAL AND
      METHODS: Two subgroups of equally complex concepts were randomly chosen to be
      taught either using traditional or self-regulation methodology. For the self
      regulation methodology, two groups were formed. One learned only through self
      regulation guidelines and the other learned through classes where the professor
      was a mediator. One hundred thirty seven freshman students from medicine,
      physical therapy, and nursing careers participated voluntarily in the study.
      RESULTS: Self-regulation methodology impacted the learning process of scientific
      concepts in a positive way and showed significant differences with traditional
      teaching. The sole use of self-regulation guidelines alone generated similar
      results, compared to those obtained by students who attended lectures.
      CONCLUSIONS: Self-regulated learning would improve in learning efficiency and
      would reduce face-to-face class time.

PMID- 25052277
TI  - [Subglottic tracheal stenosis in Wegener disease. Report of two cases].
AB  - Granulomatosis with polyangiitis (GPA) or Wegener's disease is characterized by a
      granulomatous vasculitis of the upper and lower airways and kidney. It involves
      the lower respiratory tract causing subglottic tracheal stenosis, which occurs in
      approximately 22% of patients. We report two females aged 40 and 52 years,
      admitted to the hospital with a subglottic tracheal stenosis. Their symptoms and
      management are reviewed. The first patient responded to rituximab. The second
      patient required a tracheostomy.

PMID- 25052278
TI  - [Reversible neurotoxicity secondary to metronidazole: report of one case].
AB  - Metronidazole can cause adverse effects both in the central and peripheral
      nervous system. We report a 34-year-old female who presented a reversible
      cerebellar syndrome and peripheral neuropathy as an adverse effect associated
      with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed
      hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without
      contrast enhancement or mass effect, isointense in diffusion-weighted imaging and
      hypointense in apparent diffusion coefficient sequences. Also,
      electrophysiological evaluation was consistent with axonal polyneuropathy. She
      had received metronidazole for a liver abscess during 49 days. After
      discontinuation of metronidazole, she had rapid regression of cerebellar symptoms
      and normalization of MRI, with subsequent disappearance of peripheral symptoms.
      The brain MRI, electromyography and nerve conduction studies performed at 35
      months later showed complete resolution of the lesions. Although metronidazole
      neurotoxicity is a rare event, it must be borne in mind because the prognosis is
      usually favorable after stopping the drug. 

PMID- 25052279
TI  - [Spontaneous coronary artery dissection in the post partum: report of one case].
AB  - Coronary artery dissection is a rare cause of acute coronary syndrome. Most cases
      occur in women during the peripartum period, most likely influenced by hormonal
      changes, hemodynamic stress and modifications in the immune system during
      pregnancy. The pathogenesis of coronary artery dissection is unknown, hence
      numerous theories have been postulated such as pregnancy-related conditions, the
      presence of connective tissue disorders, trauma, etc. The clinical presentation
      ranges from asymptomatic patients to the whole spectrum of acute coronary
      syndrome manifestations. The management of these patients requires a
      multidisciplinary approach, with two options: medical therapy or an invasive
      approach, with percutaneous coronary intervention or coronary artery bypass graft
      surgery. The choice of treatment options depends on the hemodynamic status of the
      patient, the extension of the dissection and the myocardial territory at risk. In
      this case report we present a 38-year-old female who had a coronary artery
      dissection seven days postpartum. Coronary catheterization showed dissection of
      the left main coronary artery that extended until the circumflex artery. An intra
      aortic balloon pump was installed and the patient then underwent coronary artery
      bypass graft surgery, with satisfactory results. 

PMID- 25052280
TI  - [Raul B. Etcheverry, M.D. (1909-2014)].
AB  - Professor Raul B. Etcheverry, M.D., was a founder of Chilean Hematology back in
      the 1940's and a practicing physician and teacher until an advanced age. Being a
      superb clinician, he was admired by his ability to unveil from the most common to
      the most difficult diagnosis of blood disorders and neoplasms by examining blood
      smears and cytology samples. He trained in Hematology a large number of
      physicians and technicians coming from several countries in Latin America as well
      as from Chile. Besides medicine, he conducted seminal studies to unveil ethnic
      characteristics of the original inhabitants of Chile identifying blood groups and
      other genetic markers in mummies and in current living descendants, from Northern
      and Southern Chile and from Easter Island. He was a prominent scholar that was
      awarded high titles and distinctions from the University of Chile, the Chilean
      Academy of Medicine, the Chilean Government, and several hematological societies
      from Chile and other countries. After 104 years of fruitful life, he passed away
      leaving a vast number of disciples and admirers. 

PMID- 25052281
TI  - [Solidarity fund for medicaments: does it represent a good use of health
      resources?].

PMID- 25052283
TI  - [Publication culture: two different realities].

PMID- 25052282
TI  - [Not to forget interaction between meropenem and valproic acid].

PMID- 25052284
TI  - [Parkinson disease mortality rates in Chile: an under-reported condition].

PMID- 25052285
TI  - [Diagnostic and Interventional Nephrology Committee of the Chilean Society of
      Nephrology].

PMID- 25052286
TI  - Should be prescribed lacosamide in patients with Lennox-Gastaut syndrome?

PMID- 25052288
TI  - Efficacy and tolerability of add-on Lacosamide in children with Lennox-Gastaut
      syndrome.

PMID- 25052287
TI  - Use of lacosamide in Lennox-Gastaut syndrome: is it too premature?

PMID- 25052289
TI  - Regression modeling of longitudinal data with outcome-dependent observation
      times: extensions and comparative evaluation.
AB  - Conventional longitudinal data analysis methods assume that outcomes are
      independent of the data-collection schedule. However, the independence assumption
      may be violated, for example, when a specific treatment necessitates a different
      follow-up schedule than the control arm or when adverse events trigger additional
      physician visits in between prescheduled follow-ups. Dependence between outcomes
      and observation times may introduce bias when estimating the marginal association
      of covariates on outcomes using a standard longitudinal regression model. We
      formulate a framework of outcome-observation dependence mechanisms to describe
      conditional independence given observed observation-time process covariates or
      shared latent variables. We compare four recently developed semi-parametric
      methods that accommodate one of these mechanisms. To allow greater flexibility,
      we extend these methods to accommodate a combination of mechanisms. In simulation
      studies, we show how incorrectly specifying the outcome-observation dependence
      may yield biased estimates of covariate-outcome associations and how our proposed
      extensions can accommodate a greater number of dependence mechanisms. We
      illustrate the implications of different modeling strategies in an application to
      bladder cancer data. In longitudinal studies with potentially outcome-dependent
      observation times, we recommend that analysts carefully explore the conditional
      independence mechanism between the outcome and observation-time processes to
      ensure valid inference regarding covariate-outcome associations.

PMID- 25052290
TI  - Comparison of the ablation ability of nucleus pulposus after 1,064 nm Nd:YAG
      laser and 980 nm diode laser radiation.
AB  - OBJECTIVE: To compare the ablation ability of nucleus pulposus after 1,064 nm
      Nd:YAG laser and 980 nm diode laser radiation. METHODS: Goat spine specimen (GSS)
      was radiated using Nd:YAG laser and 980 nm diode laser and then divided into five
      groups based on the final energy--200, 400, 600, 800 and 1,000 J groups. The
      ablation quality of nucleus pulposus after radiation was recorded. RESULTS: The
      ablation quality of GSS was greater at higher radiation energies in both lasers.
      When compared at the same energy level, the ablation quality of GSS was greater
      in 980 nm diode laser than in 1,064 nm Nd:YAG laser. Statistical significance was
      observed in 200 and 400 J groups (P < 0.05) and in 600, 800 and 1,000 J groups (P
      < 0.01). CONCLUSION: Radiation with 980 nm diode laser showed better ablation
      ability than 1,064 nm Nd:YAG laser.

PMID- 25052291
TI  - Caloric restriction reveals a metabolomic and lipidomic signature in liver of
      male mice.
AB  - Lipid composition, particularly membrane unsaturation, has been proposed as being
      a lifespan determinant, but it is currently unknown whether caloric restriction
      (CR), an accepted life-extending intervention, affects cellular lipid profiles.
      In this study, we employ a liquid chromatography quadrupole time-of-flight-based
      methodology to demonstrate that CR in the liver of male C57BL/6 mice: (i) induces
      marked changes in the cellular lipidome, (ii) specifically reduces levels of a
      phospholipid peroxidation product, 1-palmitoyl-2-glutaryl-sn-glycero-3
      phosphatidylcholine, (iii) alters cellular phosphoethanolamine and triglyceride
      distributional profiles, (iv) affects mitochondrial electron transport chain
      complexes, increasing complex II and decreasing complex III and (v) is associated
      with specific changes in liver metabolic pathways. These data demonstrate that CR
      induces a specific lipidome and metabolome reprogramming event in mouse liver
      which is associated with lower protein oxidative damage, as assessed by mass
      spectrometry-based measurements. Such changes may be critical to the increased
      lifespan and healthspan observed in C57BL/6 mice following CR. 

PMID- 25052292
TI  - Interprofessional learning (IPL) in medical education--are we capitalising fully?

PMID- 25052293
TI  - Real-time in situ monitoring of poly(lactide-co-glycolide) coating of coronary
      stents using electrochemical impedance spectroscopy.
AB  - Monitoring erosion progress of biodegradable drug carrying polymer coated on
      coronary drug eluting stents (DES) is largely hindered because of the small
      amount of coating material as well as the irregular profile of coating, both of
      which make the monitoring using traditional methods highly challenging. In our
      study, electrochemical impedance spectroscopy (EIS), a widely used method in the
      study of metal corrosion, was used to address the challenges traditional methods
      face. In vitro, remained mass and molecular weight drop data of film-like
      poly(lactide-co-glycolide) (PLGA) samples due to degradation were monitored using
      traditional mass loss measurement and size exclusion chromatography (SEC)
      methods. The obtained data were compared to the changes of capacitance and
      impedance measured by EIS from PLGA-coated stainless slices with an equivalent
      electrical circuit model. The results showed that the changes of the resistance
      and capacitance obtained by EIS, which indicates transformations of PLGA coating,
      can be correlated to the degradation measured by traditional methods, such as
      SEC. Furthermore, EIS method was applied to monitor and evaluate the erosion
      progress of a real stent with PLGA coating. Our results suggested that EIS method
      can accurately monitor real-time erosion process of thin polymer coatings on DES
      in situ.

PMID- 25052294
TI  - The quest for a simple bioactive analog of paclitaxel as a potential anticancer
      agent.
AB  - Paclitaxel (PTX), introduced into the clinic in 1991, has revealed itself as an
      effective antimicrotubule drug for treatment of a range of otherwise intractable
      cancers. Along with docetaxel (DTX) and in combination with other agents such as
      cisplatin, it has proven to be a first-line therapy. Unfortunately, PTX and DTX
      carry severe liabilities such as debilitating side effects, rapid onset of
      resistance, and rather complex molecular structures offering substantial
      challenges to ease of synthetic manipulation. Consequently, the past 15 years has
      witnessed many efforts to synthesize and test highly modified analogs based on
      intuitive structural similarity relationships with the PTX molecular skeleton, as
      well as efforts to mimic the conformational profile of the ligand observed in the
      macromolecular tubulin-PTX complex. Highly successful improvements in potency, up
      to 50-fold increases in IC50, have been achieved by constructing bridges between
      distal centers in PTX that imitate the conformer of the electron crystallographic
      binding pose. Much less successful have been numerous attempts to truncate PTX by
      replacing the baccatin core with simpler moieties to achieve PTX-like potencies
      and applying a wide range of flexible synthesis-based chemistries. Reported
      efforts, characterized by a fascinating array of baccatin substitutes, have
      failed to surpass the bioactivities of PTX in both microtubule disassembly assays
      and cytotoxicity measurements against a range of cell types. Most of the
      structures retain the main elements of the PTX C13 side chain, while seeking a
      smaller rigid bicycle as a baccatin replacement adorned with substituents to
      mimic the C2 benzoyl moiety and the oxetane ring. We surmise that past studies
      have been handicapped by solubility and membrane permeability issues, but
      primarily by the existence of an expansive taxane binding pocket and the
      discrepancy in molecular size between PTX and the pruned analogs. A number of
      these molecules offer molecular volumes 50-60% that of PTX, fewer contacts with
      the tubulin protein, severe mismatches with the PTX pharmacophore, lessened
      capacity to dispel binding site waters contributing to DeltaGbind, and
      unanticipated binding poses. The latter is a critical drawback if molecular
      designs of simpler PTX structures are based on a perceived or known PTX binding
      conformation. We conclude that design and synthesis of a highly cytotoxic tubulin
      assembly agent based on the paclitaxel pharmacophore remains an unsolved
      challenge, but one that can be overcome by focus on the architecture of the
      taxane binding site independent of the effective, but not unique, hand-in-glove
      match represented by the PTX-tubulin complex.

PMID- 25052295
TI  - Curriculum design for pediatric radiology in Ethiopia.

PMID- 25052296
TI  - Dynamic contrast-enhanced MRI in mice: an investigation of model parameter
      uncertainties.
AB  - PURPOSE: To establish the experimental factors that dominate the uncertainty of
      hemodynamic parameters in commonly used pharmacokinetic models. METHODS: By
      fitting simulation results from a multiregion tissue exchange model (Multiple
      path, Multiple tracer, Indicator Dilution, 4 region), the precision and accuracy
      of hemodynamic parameters in dynamic contrast-enhanced MRI with four tracer
      kinetic models is investigated. The impact of various injection rates as well as
      imprecise knowledge of the arterial input functions is examined. RESULTS: Fast
      injections are beneficial for K(trans) precision within the extended Tofts model
      and within the two-compartment exchange model but do not affect the other models
      under investigation. Biases from errors in the arterial input functions are
      mostly consistent in size and direction for the simple and the extended Tofts
      model, while they are hardly predictable for the other models. Errors in the
      hematocrit introduce the greatest loss in parameter accuracy, amounting to an
      average K(trans) bias of 40% for a 30% overestimation throughout all models.
      CONCLUSION: This simulation study allows the detailed inspection of the isolated
      impact from various experimental conditions on parameter uncertainty. Because
      parameter uncertainty comparable to human studies was found, this study
      represents a validation of preclinical dynamic contrast-enhanced MRI for modeling
      human tumor physiology.

PMID- 25052297
TI  - A prospective study of the relationship between sense of coherence, depression,
      anxiety, and quality of life of haematopoietic stem cell transplant patients over
      time.
AB  - OBJECTIVES: The primary aim of this study was to examine the impact of patient
      sense of coherence (SOC) on anxiety and depressive symptoms, and quality of life
      (QoL) dimensions in the acute phase of haematopoietic stem cell transplantation
      (HSCT). A secondary aim was to determine if SOC measured pre-transplant was
      predictive of psychological distress and QoL post-transplantation, after
      controlling for physical wellbeing. METHOD: A series of measures was completed by
      60 HSCT patients prior to transplantation. Follow-up data were collected at 2-3
      weeks and 3 months post-transplantation. Measures administered included the Brief
      Symptom Inventory-18, Orientation to Life Questionnaire, and Functional
      Assessment of Cancer Therapy-Bone Marrow Transplantation. RESULTS: When compared
      across the three time points, depression levels, and physical and functional
      wellbeing were worst at 2-3 weeks post-transplantation. SOC was positively
      associated with physical wellbeing prior to HSCT but not after transplantation.
      Weaker SOC predicted higher levels of depression, and poorer social, emotional,
      and functional wellbeing at both follow-up points, after accounting for physical
      wellbeing. CONCLUSIONS: Given that SOC was related to depression and QoL
      dimensions post-transplantation, it may be important for health care
      professionals to conduct psychosocial assessments to determine patient SOC. This
      would enable provision of tailored psychological support prior to and following
      stem cell transplantation.

PMID- 25052298
TI  - Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3: a review
      and recommendations for accurate reporting.
AB  - Malaria rapid diagnostic tests (RDTs) play a critical role in malaria case
      management, surveillance and case investigations. Test performance is largely
      determined by design and quality characteristics, such as detection sensitivity,
      specificity, and thermal stability. However, parasite characteristics such as
      variable or absent expression of antigens targeted by RDTs can also affect RDT
      performance. Plasmodium falciparum parasites lacking the PfHRP2 protein, the most
      common target antigen for detection of P. falciparum, have been reported in some
      regions. Therefore, accurately mapping the presence and prevalence of P.
      falciparum parasites lacking pfhrp2 would be an important step so that RDTs
      targeting alternative antigens, or microscopy, can be preferentially selected for
      use in such regions. Herein the available evidence and molecular basis for
      identifying malaria parasites lacking PfHRP2 is reviewed, and a set of
      recommended procedures to apply for future investigations for parasites lacking
      PfHRP2, is proposed. 

PMID- 25052299
TI  - Hybrid multiwalled carbon nanotube--Laponite sorbent for removal of methylene
      blue from aqueous solutions.
AB  - The article discusses adsorption of methylene blue dye by novel hybrid sorbent
      consisting of Laponite and multiwalled carbon nanotubes. The sorbent was obtained
      by sonication of the aqueous suspensions of nanotubes at different concentrations
      of Laponite. The methods of the methylene blue adsorption, dead-end membrane
      filtration and environmental scanning electron microscopy were used for the
      sorbent characterization. It may be concluded from the results of filtration and
      adsorption experiments that sonication of mixed aqueous suspensions of Laponite
      and multiwalled carbon nanotubes leads to the formation of hybrid particles (ML
      particles) with a core-shell structure. The size and the shape of hybrid
      particles were determined by nanotubes, while their adsorption properties were
      determined by Laponite particles attached to the surface of nanotubes. The
      Laponite content in hybrid particles was corresponding to the Laponite to
      nanotubes ratio in the initial suspension X(L)=0-1. Due to the presence of
      Laponite in the sorbent, its adsorbing capacity was much higher as compared to
      the adsorbing capacity of pure nanotubes, and it was directly proportional to the
      Laponite content. This sorbent may be used either as a purifying additive or as a
      filtering layer if it is deposited on the surface of a supporting membrane. Due
      to relatively large size of hybrid particles, they can be easily separated from
      the purified solution by filtration or centrifugation.

PMID- 25052300
TI  - Surgical treatment of solid pseudopapillary neoplasms of the pancreas and risk
      factors for malignancy.
AB  - BACKGROUND: The aim of this study was to identify clinical predictors of
      malignancy and surgical strategies for pancreatic solid pseudopapillary neoplasm
      (SPN) by analysis of surgical outcomes at a single institution. METHODS: All
      patients who underwent surgery for SPN between 1995 and 2010 were identified.
      Histopathology slides of all patients were reviewed by a specialized pathologist
      and the neoplasms were classified according to the criteria of the World Health
      Organization 2010. RESULTS: Of the 106 patients identified, 85 (80.2 per cent)
      were female, and the median age was 36 (range 10-65) years. Median tumour size
      was 4.5 (range 1.0-15.0) cm. Some 17 patients (16.0 per cent) were classified as
      having a high-grade malignant SPN. Tumour size of at least 5 cm was associated
      with high-grade malignant potential (P = 0.022). Although lymph nodes were
      removed from 40 patients (37.7 per cent), there were no nodal metastases. A total
      of five patients underwent en bloc resection of adjacent structures, including
      two with portal vein involvement. After a median follow-up of 56.9 months, two
      patients with high-grade malignant SPN had evidence of tumour recurrence in the
      lymph nodes and liver. CONCLUSION: SPN with a diameter of 5 cm or more is
      associated with a high-grade malignant phenotype. Complete surgical removal is
      associated with low recurrence rates.

PMID- 25052302
TI  - Assessing the uptake of the Liverpool Care Pathway for dying patients: a
      systematic review.

PMID- 25052303
TI  - Palliative care research in the francophone world.

PMID- 25052304
TI  - [Upper nasolabial flap: improving the surgical technique].
AB  - The upper nasolabial flap was initially described by Kilner in 1937, and
      popularized by Preaux in 1994. It is an interesting solution for the
      reconstruction of the ala thanks to its simplicity and reliability. Nevertheless,
      the results obtained with the original technique could be improved because of
      scars on the side of the nose and the absence of nostril groove. That is why we
      propose a modification of the surgical technique. We present the case of an 82
      year-old female patient who presented with a basal cell carcinoma of the right
      nasal wing rebuilt by a modified upper nasolabial flap. The skin triangle above
      the defect, which separated it from the flap pedicle, was not sacrificed but
      dissected forward from behind, to the junction between the nasal dorsum and the
      lateral side of the nose. The next step, key step of our technique, was removing
      the epidermis from the flap pedicle. The nasolabial flap was thus slid forward to
      the alar loss of substance, thereby recreating a nostril groove nose with a
      single scar. The scar was thus more discrete than with the conventional
      technique. The other steps did not differ from the conventional technique. The
      immediate postoperative course was uneventful. Rebuilding a loss of transfixing
      matter of the ala with a modified Preaux flap technique allows obtaining a
      simple, reliable, and elegant reconstruction. It presents all the advantages of
      the conventional upper nasolabial flap with particular care given to the cosmetic
      appearance of nasal reconstruction.

PMID- 25052305
TI  - Resource effects on denitrification are mediated by community composition in
      tidal freshwater wetlands soils.
AB  - Accurate prediction of denitrification rates remains difficult, potentially owing
      to complex uncharacterized interactions between resource conditions and
      denitrifier communities. To better understand how the availability of organic
      matter (OM) and nitrate (NO3 (-) ), two of the resources most fundamental to
      denitrifiers, affect these populations and their activity, we performed an in
      situ resource manipulation in tidal freshwater wetland soils. Soils were
      augmented with OM to double ambient concentrations, using either compost or plant
      litter, and fertilized with KNO3 at two levels (low: ~ 5 mg l(-1)  NO3 (-) -N and
      high: ~ 50 mg l(-1)  NO3 (-) -N) in a full factorial design. Community
      composition of nirS-denitrifers (assessed using terminal restriction fragment
      length polymorphism) was interactively regulated by both NO3 (-) concentration
      and OM type, and the associated shifts in community composition were relatively
      consistent across sampling dates (6, 9 and 12 months of incubation).
      Denitrification potential (pDNF) rates were also strongly affected by NO3 (-)
      fertilization and increased by ~ 10-100-fold. Path analysis revealed that the
      influence of resource availability on pDNF rates was largely mediated through
      changes in nirS-denitrifier community composition. These results suggest that a
      greater understanding of denitrifier community ecology may enable more accurate
      prediction of denitrification rates.

PMID- 25052306
TI  - Bortezomib-thalidomide-based regimens improved clinical outcomes without
      increasing toxicity as induction treatment for untreated multiple myeloma: a meta
      analysis of phase III randomized controlled trials.
AB  - Novel agents thalidomide and bortezomib have significantly improved myeloma
      treatment. However, it remains unclear whether patients will benefit more from
      the combination therapy of these two agents. Our meta-analysis aims to compare
      the efficiency, and more importantly, the safety of bortezomib-thalidomide-based
      (VT-based) versus bortezomib-based or thalidomide-based (V-based/T-based)
      regimens as induction therapy in patients with previously untreated myeloma.
      Overall, five phase III RCTs including 1765 patients were identified. Compared
      with V-based or T-based regimens, VT-based regimens significantly improved CR
      (OR=2.22, 95% CI [1.44, 3.43]), ORR (OR=2.19, 95% CI [1.51, 3.19]) as well as PFS
      (HR=0.69, 95% CI [0.54, 0.88]), but not OS (HR=1.04, 95% CI [0.91, 1.19]).
      Notably, most expected side effects of bortezomib or thalidomide were comparable
      in both groups, including hematologic (anemia, neutropenia, thrombocytopenia),
      nonhematologic (peripheral neuropathy, deep venous thrombosis, infections,
      gastrointestinal events) side effects and discontinuation during or after
      induction therapy. These results suggest that combination of thalidomide and
      bortezomib might be a better first-line choice for patients with untreated
      myeloma.

PMID- 25052308
TI  - Transcript variants of RUNX1T1: new insight into t(8;21)-positive leukemia.

PMID- 25052307
TI  - Systemic lupus erythematosus is associated with increased incidence of
      hematologic malignancies: a meta-analysis of prospective cohort studies.
AB  - Our objective was to define the risk of lymphoma, leukemia and myeloma in adult
      patients with SLE with a meta-analysis of prospective cohort studies. A
      literature search from 1995 to 2013 revealed eight studies evaluating this
      association. The outcome of interest was the standardized incidence ratio (SIR).
      Our study included 401 cases in a cohort of approximately 68,000 SLE patients,
      and showed an increased incidence of all hematologic malignancies (SIR 2.9), non
      Hodgkin lymphoma (SIR 5.7), Hodgkin lymphoma (SIR 3.1), leukemia (SIR 2.3) and
      myeloma (SIR 1.5) in SLE patients compared with the general population. The
      increased SIR was consistent regardless of age, sex or geographical region. 

PMID- 25052309
TI  - The FSHB -211G>T variant attenuates serum FSH levels in the supraphysiological
      gonadotropin setting of Klinefelter syndrome.
AB  - Klinefelter syndrome (47, XXY) is the most frequent genetic cause of male
      infertility and individuals share the endocrine hallmark of hypergonadotropic
      hypogonadism. Single-nucleotide polymorphisms located within the FSHB/FSHR gene
      were recently shown to impact serum follicle-stimulating hormone (FSH) levels and
      other reproductive parameters in men. The objective of this study was to analyse
      the effect of FSHB-211G>T (c.-280G>T, rs10835638) as well as FSHR c.2039G>A
      (rs6166) and FSHR c.-29G>A (rs1394205) on endocrine and reproductive parameters
      in untreated and testosterone-treated Klinefelter patients. Patients were
      retrospectively selected from the clientele attending a university-based
      andrology centre. A total of 309 non-mosaic Klinefelter individuals between 18
      and 65 years were included and genotyped for the variants by TaqMan assays. The
      untreated group comprised 248 men, in which the FSHB -211G>T allele was
      significantly associated with the reduced serum follicle-stimulating hormone
      levels (-6.5 U/l per T allele, P=1.3 * 10(-3)). Testosterone treatment (n=150)
      abolished the observed association. When analysing patients before and under
      testosterone treatment (n=89), gonadotropin levels were similarly suppressed
      independently of the FSHB genotype. The FSHR polymorphisms did not exhibit any
      significant influence in any group, neither on the endocrine nor reproductive
      parameters. In conclusion, a hypergonadotropic setting such as Klinefelter
      syndrome does not mask the FSHB -211G>T genotype effects on the follicle
      stimulating hormone serum levels. The impact was indeed more pronounced compared
      with normal or infertile men, whereas gonadotropin suppression under testosterone
      treatment seems to be independent of the genotype. Thus, the FSHB -211G>T
      genotype is a key determinant in the regulation of gonadotropins in different
      reproductive-endocrine pathopyhsiologies. 

PMID- 25052310
TI  - Clinical utility gene card for: ALG6 defective congenital disorder of
      glycosylation.

PMID- 25052311
TI  - Evaluation of European coeliac disease risk variants in a north Indian
      population.
AB  - Studies in European populations have contributed to a better understanding of the
      genetics of complex diseases, for example, in coeliac disease (CeD), studies of
      over 23 000 European samples have reported association to the HLA locus and
      another 39 loci. However, these associations have not been evaluated in detail in
      other ethnicities. We sought to better understand how disease-associated loci
      that have been mapped in Europeans translate to a disease risk for a population
      with a different ethnic background. We therefore performed a validation of
      European risk loci for CeD in 497 cases and 736 controls of north Indian origin.
      Using a dense-genotyping platform (Immunochip), we confirmed the strong
      association to the HLA region (rs2854275, P=8.2 * 10(-49)). Three loci showed
      suggestive association (rs4948256, P=9.3 * 10(-7), rs4758538, P=8.6 * 10(-5) and
      rs17080877, P=2.7 * 10(-5)). We directly replicated five previously reported
      European variants (P<0.05; mapping to loci harbouring FASLG/TNFSF18,
      SCHIP1/IL12A, PFKFB3/PRKCQ, ZMIZ1 and ICOSLG). Using a transferability test, we
      further confirmed association at PFKFB3/PRKCQ (rs2387397, P=2.8 * 10(-4)) and
      PTPRK/THEMIS (rs55743914, P=3.4 * 10(-4)). The north Indian population has a
      higher degree of consanguinity than Europeans and we therefore explored the role
      of recessively acting variants, which replicated the HLA locus (rs9271850, P=3.7
      * 10(-23)) and suggested a role of additional four loci. To our knowledge, this
      is the first replication study of CeD variants in a non-European population. 

PMID- 25052312
TI  - Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy.
AB  - We assessed a large consanguineous Pakistani family (PKAB157) segregating early
      onset low vision problems. Funduscopic and electroretinographic evaluation of
      affected individuals revealed juvenile cone-rod dystrophy (CRD) with maculopathy.
      Other clinical symptoms included loss of color discrimination, photophobia and
      nystagmus. Whole-exome sequencing, segregation and haplotype analyses
      demonstrated that a transition variant (c.955T>C; p.(Cys319Arg)) in CNGA3 co
      segregated with the CRD phenotype in family PKAB157. The ability of CNGA3 channel
      to influx calcium in response to agonist, when expressed either alone or together
      with the wild-type CNGB3 subunit in HEK293 cells, was completely abolished due to
      p.Cys319Arg variant. Western blotting and immunolocalization studies suggest that
      a decreased channel density in the HEK293 cell membrane due to impaired folding
      and/or trafficking of the CNGA3 protein is the main pathogenic effect of the
      p.Cys319Arg variant. Mutant alleles of the human cone photoreceptor cyclic
      nucleotide-gated channel (CNGA3) are frequently associated with achromatopsia. In
      rare cases, variants in CNGA3 are also associated with cone dystrophy, Leber's
      congenital amaurosis and oligo cone trichromacy. The identification of predicted
      p.(Cys319Arg) missense variant in CNGA3 expands the repertoire of the known
      genetic causes of CRD and phenotypic spectrum of CNGA3 alleles. 

PMID- 25052313
TI  - Parental age effects, but no evidence for an intrauterine effect in the
      transmission of myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG
      repeat (g.17294_17296(45_1000)) with more repeats associated with increased
      disease severity and reduced age at onset. Expanded disease-associated alleles
      are highly unstable in both the germline and soma. Germline instability is
      expansion biased, providing a molecular explanation for anticipation. Somatic
      instability is expansion biased, size- and age-dependent, features that have
      compromised genotype-phenotype correlations and intergenerational studies. We
      corrected these confounding factors by estimating the progenitor allele length in
      54 father-offspring and 52 mother-offspring pairs in Costa Rican DM1 families.
      Not surprisingly, we found major parental allele length effects on the size of
      the allele transmitted, the magnitude of the intergenerational length change, the
      age at onset in the next generation and the degree of anticipation in both male
      and female transmissions. We also detected, for the first time, an age-of-parent
      effect for both male and female transmission. Interestingly, we found no evidence
      for an intrauterine effect in the transmission of congenital DM1, suggesting
      previous reports may have been an artefact of age-dependent somatic instability
      and sampling bias. These data provide new insights into the germline dynamics of
      the CTG repeat and opportunities for providing additional advice and more
      accurate risk assessments to prospective parents in DM1 families. 

PMID- 25052314
TI  - Functional correction by antisense therapy of a splicing mutation in the GALT
      gene.
AB  - In recent years, antisense therapy has emerged as an increasingly important
      therapeutic approach to tackle several genetic disorders, including inborn errors
      of metabolism. Intronic mutations activating cryptic splice sites are
      particularly amenable to antisense therapy, as the canonical splice sites remain
      intact, thus retaining the potential for restoring constitutive splicing.
      Mutational analysis of Portuguese galactosemic patients revealed the intronic
      variation c.820+13A>G as the second most prevalent mutation, strongly suggesting
      its pathogenicity. The aim of this study was to functionally characterize this
      intronic variation, to elucidate its pathogenic molecular mechanism(s) and,
      ultimately, to correct it by antisense therapy. Minigene splicing assays in two
      distinct cell lines and patients' transcript analyses showed that the mutation
      activates a cryptic donor splice site, inducing an aberrant splicing of the GALT
      pre-mRNA, which in turn leads to a frameshift with inclusion of a premature stop
      codon (p.D274Gfs*17). Functional-structural studies of the recombinant wild-type
      and truncated GALT showed that the latter is devoid of enzymatic activity and
      prone to aggregation. Finally, two locked nucleic acid oligonucleotides, designed
      to specifically recognize the mutation, successfully restored the constitutive
      splicing, thus establishing a proof of concept for the application of antisense
      therapy as an alternative strategy for the clearly insufficient dietary treatment
      in classic galactosemia. 

PMID- 25052315
TI  - EMQN Best Practice Guidelines for molecular and haematology methods for carrier
      identification and prenatal diagnosis of the haemoglobinopathies.
AB  - Haemoglobinopathies constitute the commonest recessive monogenic disorders
      worldwide, and the treatment of affected individuals presents a substantial
      global disease burden. Carrier identification and prenatal diagnosis represent
      valuable procedures that identify couples at risk for having affected children,
      so that they can be offered options to have healthy offspring. Molecular
      diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and
      patients (especially 'atypical' cases who often have complex genotype
      interactions). However, the haemoglobin disorders are unique among all genetic
      diseases in that identification of carriers is preferable by haematological
      (biochemical) tests rather than DNA analysis. These Best Practice guidelines
      offer an overview of recommended strategies and methods for carrier
      identification and prenatal diagnosis of haemoglobinopathies, and emphasize the
      importance of appropriately applying and interpreting haematological tests in
      supporting the optimum application and evaluation of globin gene DNA analysis. 

PMID- 25052317
TI  - Distal single subcortical infarction had a better clinical outcome compared with
      proximal single subcortical infarction.
AB  - BACKGROUND AND PURPOSE: Single subcortical infarction (SSI) may be classified as
      proximal SSI (pSSI) or distal SSI (dSSI) according to its location within the
      middle cerebral artery territory. Few studies have examined the differences in
      clinical outcome between the two. Our study investigated such differences in
      patients with pSSI or dSSI and examined their baseline characteristics and
      indicators for small-vessel disease. METHODS: We prospectively enrolled 400
      patients with SSI (208 pSSI and 192 dSSI) who had no middle cerebral artery
      disease on MR angiography. Data compared included clinical information, lesion
      size, prevalence of lacune and leukoaraiosis at baseline, National Institutes of
      Health Stroke Scale score and modified Rankin Scale score at discharge, and any
      deterioration during admission or recurrence of ischemic stroke <1 year. RESULTS:
      In multivariable logistic regression analysis, dSSI was independently associated
      with patient's history of stroke, admission National Institutes of Health Stroke
      Scale score <=3, Fazekas score >=3, presence of lacune, but not hyperlipidemia.
      Patients with dSSI had shorter length of hospital stay, lower rate of functional
      dependence at discharge (modified Rankin Scale score >=2), and lower
      deterioration or recurrence risk of ischemic stroke in 1 year. Multivariable
      logistic regression analysis showed that factors associated with higher
      deterioration or recurrence risk of ischemic stroke at 1 year included female
      sex, history of coronary heart disease, pSSI, and not on antithrombotics <48
      hours of admission. CONCLUSIONS: Compared with pSSI, patients with dSSI likely
      had small-vessel diseases but better clinical outcome.

PMID- 25052318
TI  - Flow diversion versus conventional treatment for carotid cavernous aneurysms.
AB  - BACKGROUND AND PURPOSE: Several endovascular treatment options are available for
      cavernous carotid aneurysms. We compared pipeline embolization device (PED)
      versus conventional endovascular treatment in terms of evolution of mass effect,
      complications, recurrence, and retreatment rate. METHODS: One hundred fifty-seven
      patients harboring 167 cavernous carotid aneurysms were treated using PED
      placement, coiling, stent-assisted coiling, and carotid vessel destruction.
      Procedural complications, angiographic results, and clinical outcomes were
      analyzed and compared. RESULTS: There were no difference in age, sex, and mean
      aneurysm size between those treated with PED and those treated with conventional
      endovascular procedures. The patients treated with PED had a significantly lower
      proportion of small-size aneurysms (<10 mm) and a shorter follow-up duration.
      Multivariate analysis revealed treatment other than PED (PED: odds ratio [OR],
      0.03; P=0.002) and size >15 mm (OR, 4.27; P=0.003) to be predictors of no
      improvement in symptoms. The rate of complete occlusion was 81.36% (48 of 59) for
      PED, 42.25% (39 of 71) for stent-assisted coiling, 27.27% (6 of 22) for coiling,
      and 73.33% (11 of 15) for carotid vessel destruction. Retreatment was needed in
      patients with aneurysm size >15 mm (OR, 2.67; P=0.037) and those who were not
      treated with PED (PED: OR, 0.16; P=0.006). The rate of major complications was
      6.6% (11 of 167). Patients who were treated with PED or stent-assisted coiling
      had 3.84 lower odds to develop complications (OR, 0.26; P<0.05). CONCLUSIONS: The
      use of PED should be encouraged, especially in symptomatic patients. We found PED
      to be associated with less need for future treatment, higher improvement in
      symptoms rate, and lower rate of complications.

PMID- 25052316
TI  - Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42
      cases.
AB  - Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3
      have recently been associated with heterozygous gain-of-function mutations in one
      of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode
      beta- and gamma-actins. We present detailed phenotypic descriptions and
      neuroimaging on 36 patients analyzed by our group and six cases from the
      literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major
      clinical anomalies are striking dysmorphic facial features with hypertelorism,
      broad nose with large tip and prominent root, congenital non-myopathic ptosis,
      ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in
      many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex,
      congenital heart defects and renal tract anomalies are seen in some cases.
      Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and
      around 60% of those with ACTB mutations have some degree of pachygyria with
      anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia.
      Reduction of shoulder girdle muscle bulk and progressive joint stiffness is
      common. Early muscular involvement, occasionally with congenital arthrogryposis,
      may be present. Progressive, severe dystonia was seen in one family. Intellectual
      disability and epilepsy are variable in severity and largely correlate with CNS
      anomalies. One patient developed acute lymphocytic leukemia, and another a
      cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing
      disorders. Considering the multifaceted role of actins in cell physiology, we
      hypothesize that some clinical manifestations may be partially mutation specific.
      Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for
      this clinical entity. 

PMID- 25052319
TI  - Atrial fibrillation and cognitive decline-the role of subclinical cerebral
      infarcts: the atherosclerosis risk in communities study.
AB  - BACKGROUND AND PURPOSE: The mechanism underlying the association of atrial
      fibrillation (AF) with cognitive decline in stroke-free individuals is unclear.
      We examined the association of incident AF with cognitive decline in stroke-free
      individuals, stratified by subclinical cerebral infarcts (SCIs) on brain MRI
      scans. METHODS: We analyzed data from 935 stroke-free participants (mean age+/
      SD, 61.5+/-4.3 years; 62% women; and 51% black) from 1993 to 1995 through 2004 to
      2006 in the Atherosclerosis Risk in Communities Study, a biracial community-based
      prospective cohort study. Cognitive testing (including the digit symbol
      substitution and the word fluency tests) was performed in 1993 to 1995, 1996 to
      1998, and 2004 to 2006 and brain MRI scans in 1993 to 1995 and 2004 to 2006.
      RESULTS: During follow-up, there were 48 incident AF events. Incident AF was
      associated with greater annual average rate of decline in digit symbol
      substitution (-0.77; 95% confidence interval, -1.55 to 0.01; P=0.054) and word
      fluency (-0.80; 95% confidence interval, -1.60 to -0.01; P=0.048). Among
      participants without SCIs on brain MRI scans, incident AF was not associated with
      cognitive decline. In contrast, incident AF was associated with greater annual
      average rate of decline in word fluency (-2.65; 95% confidence interval, -4.26 to
      -1.03; P=0.002) among participants with prevalent SCIs in 1993 to 1995. Among
      participants who developed SCIs during follow-up, incident AF was associated with
      a greater annual average rate of decline in digit symbol substitution (-1.51; 95%
      confidence interval, -3.02 to -0.01; P=0.049). CONCLUSIONS: The association of
      incident AF with cognitive decline in stroke-free individuals can be explained by
      the presence or development of SCIs, raising the possibility of anticoagulation
      as a strategy to prevent cognitive decline in AF.

PMID- 25052320
TI  - Pathogenetical subtypes of recurrent intracerebral hemorrhage: designations by
      SMASH-U classification system.
AB  - BACKGROUND AND PURPOSE: Pathogenetic classification of intracerebral hemorrhage
      (ICH), using systems such as SMASH-U (structural vascular lesions, medication,
      cerebral amyloid angiopathy [CAA], systemic disease, hypertension, or
      undetermined), is important in predicting functional outcomes and mortality in
      patients with ICH. This study aimed to compare pathogenetic subtypes between the
      first and recurrent ICH. METHODS: This study obtained data related to 4578
      consecutive acute patients with ICH from the National Taiwan University Hospital
      Stroke Registry during January 1995 to December 2013. Using the SMASH-U method,
      patients were classified into 6 subtypes. We then analyzed the outcomes of first
      ever ICH cases and pathogenetic classification of recurrent ICH. RESULTS: Among
      3785 patients who experienced first-ever ICH (male, 63.3%; mean age, 58.7+/-17.0
      years), the most common cause was hypertensive angiopathy (54.9%), followed by
      CAA (12.2%), systemic disease (12.1%), undetermined (10.1%), structural vascular
      lesions (7.8%), and medication related (2.9%). In 185 cases of recurrent ICH,
      pathogenetic differences between the 2 ICH events were observed in 34 (18.4%)
      cases, most of which were CAA to hypertensive angiopathy (n=10) or vice versa
      (n=7). The rates of ICH recurrence were highest for systemic disease-related and
      CAA-related ICH at 1, 5, 10, and 15 years after the indexed ICH event.
      CONCLUSIONS: In approximately one fifth of the recurrent patients with ICH,
      pathogenetic differences were observed between initial and recurrent events,
      particularly among those with CAA. It is possible that some patients with ICH
      with concomitant hypertensive angiopathy and CAA may have been categorized as CAA
      by the SMASH-U method.

PMID- 25052321
TI  - Fibrinolysis for intraventricular hemorrhage: an updated meta-analysis and
      systematic review of the literature.
AB  - BACKGROUND AND PURPOSE: Intraventricular hemorrhage is associated with high
      mortality and poor functional outcome. The use of intraventricular fibrinolytic
      (IVF) therapy as an intervention in intraventricular hemorrhage is an evolving
      therapy with conflicting reports in the literature. The goal of this study is to
      investigate the impact of IVF on mortality, functional outcome, ventriculitis,
      shunt dependence, and rehemorrhage. METHODS: During March and April 2014, a
      systematic literature search was performed identifying 1359 articles. Of these,
      24 met inclusion criteria. A random effects meta-analysis was performed using
      both pooled and subset analysis based on study type. RESULTS: Our meta-analysis
      demonstrated that IVF reduced mortality in intraventricular hemorrhage by nearly
      half (relative risk [RR], 0.55; 95% confidence interval [CI], 0.42-0.71;
      P<0.00001), increased the likelihood of good functional outcome by 66% (RR, 1.66;
      95% CI, 1.27-2.19; P=0.0003), and also decreased the rate of shunt dependence
      (RR, 0.62; 95% CI, 0.42-0.93; P=0.02). IVF was not found to be associated with
      increased rates of ventriculitis (RR=1.46; 95% CI, 0.77-2.76; P=0.25) or
      rehemorrhage (RR=1.06; 95% CI, 0.66-1.70; P=0.80). We detected no evidence of
      publication bias. CONCLUSIONS: Our meta-analysis showed that IVF is safe and
      could be an effective strategy for the treatment of intraventricular hemorrhage.
      It may reduce mortality, improve functional outcome, and diminish the need for
      permanent ventricular shunting, while not increasing the risk of ventriculitis or
      rehemorrhage.

PMID- 25052322
TI  - P-wave morphology and the risk of incident ischemic stroke in the Multi-Ethnic
      Study of Atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Emerging data suggest that left atrial disease may cause
      ischemic stroke in the absence of atrial fibrillation or flutter (AF). If true,
      this condition may provide a cause for many strokes currently classified as
      cryptogenic. METHODS: Among 6741 participants in the Multi-Ethnic Study of
      Atherosclerosis who were free of clinically apparent cerebrovascular or
      cardiovascular disease (including AF) at baseline, we examined the association
      between markers of left atrial abnormality on a standard 12-lead ECG-specifically
      P-wave area, duration, and terminal force in lead V1-and the subsequent risk of
      ischemic stroke while accounting for incident AF. RESULTS: During a median follow
      up of 8.5 years, 121 participants (1.8%) had a stroke and 541 participants (8.0%)
      were diagnosed with AF. In Cox proportional hazards models adjusting for
      potential baseline confounders, P-wave terminal force in lead V1 was more
      strongly associated with incident stroke (hazard ratio per 1 SD increase, 1.21;
      95% confidence interval, 1.02-1.44) than with incident AF (hazard ratio per 1 SD,
      1.11; 95% confidence interval, 1.03-1.21). The association between P-wave
      terminal force in lead V1 and stroke was robust in numerous sensitivity analyses
      accounting for AF, including analyses that excluded those with any incident AF or
      modeled any incident AF as having been present from baseline. CONCLUSIONS: We
      found an association between baseline P-wave morphology and incident stroke even
      after accounting for AF. This association may reflect an atrial cardiopathy that
      leads to stroke in the absence of AF.

PMID- 25052323
TI  - Altered astrocyte-neuronal interactions after hypoxia-ischemia in the neonatal
      brain in female and male rats.
AB  - BACKGROUND AND PURPOSE: Increased susceptibility to excitotoxicity of the
      neonatal brain after hypoxia-ischemia (HI) may be caused by limited capacity of
      astrocytes for glutamate uptake, and mitochondrial failure probably plays a key
      role in the delayed injury cascade. Male infants have poorer outcome than females
      after HI, possibly linked to differential intermediary metabolism. METHODS: [1
      (13)C]glucose and [1,2-(13)C]acetate were injected at zero, 6, and 48 hours after
      unilateral HI in 7-day-old rats. Intermediary metabolism was analyzed with
      magnetic resonance spectroscopy. RESULTS: Mitochondrial metabolism was generally
      reduced in the ipsilateral hemisphere for <=6 hours after HI, whereas
      contralaterally, it was reduced in neurons but not in astrocytes. Transfer of
      glutamate from neurons to astrocytes was increased in the contralateral, but not
      in the ipsilateral hemisphere at 0 hour, and reduced bilaterally at 6 hours after
      HI. The transfer of glutamine from astrocytes to glutamatergic neurons was
      unaltered in both hemispheres, whereas the transfer of glutamine to GABAergic
      neurons was increased ipsilaterally at 0 hour. Anaplerosis (astrocytes) was
      decreased, whereas partial pyruvate recycling (astrocytes) was increased directly
      after HI. Male pups had lower astrocytic mitochondrial metabolism than females
      immediately after HI, whereas that of females was reduced longer and encompassed
      both neurons and astrocytes. CONCLUSIONS: The prolonged depression in
      mitochondrial metabolism indicates that mitochondria are vulnerable targets in
      the delayed injury after neonatal HI. The degree of astrocytic malfunction may be
      a valid indicator of outcome after hypoxic/HI brain injury and may be linked to
      the differential outcome in males and females.

PMID- 25052324
TI  - Economic Assessment of Zoonotic Diseases: An Illustrative Study of Rift Valley
      Fever in the United States.
AB  - This study evaluates the economic consequences of a Rift Valley Fever outbreak, a
      virus that spreads from livestock to humans, often through mosquitoes. Developing
      a 'one health' economic framework, economic impacts on agricultural producers and
      consumers, government costs of response, costs and disruptions to non
      agricultural activities in the epidemiologically impacted region, and human
      health costs (morbidity and mortality) are estimated. We find the agricultural
      firms bear most of the negative economic impacts, followed by regional non
      agricultural firms, human health and government. Further, consumers of
      agricultural products benefit from small outbreaks due to bans on agricultural
      exports. 

PMID- 25052326
TI  - Degradation of polyethylene by Trichoderma harzianum--SEM, FTIR, and NMR
      analyses.
AB  - Trichoderma harzianum was isolated from local dumpsites of Shivamogga District
      for use in the biodegradation of polyethylene. Soil sample of that dumpsite was
      used for isolation of T. harzianum. Degradation was carried out using autoclaved,
      UV-treated, and surface-sterilized polyethylene. Degradation was monitored by
      observing weight loss and changes in physical structure by scanning electron
      microscopy, Fourier transform infrared spectroscopy, and nuclear magnetic
      resonance spectroscopy. T. harzianum was able to degrade treated polyethylene
      (40%) more efficiently than autoclaved (23%) and surface-sterilized polyethylene
      (13%). Enzymes responsible for polyethylene degradation were screened from T.
      harzianum and were identified as laccase and manganese peroxidase. These enzymes
      were produced in large amount, and their activity was calculated using
      spectrophotometric method and crude extraction of enzymes was carried out.
      Molecular weight of laccase was determined as 88 kDa and that of manganese
      peroxidase was 55 kDa. The capacity of crude enzymes to degrade polyethylene was
      also determined. By observing these results, we can conclude that this organism
      may act as solution for the problem caused by polyethylene in nature.

PMID- 25052325
TI  - The accuracy of self-reported drug ingestion histories in emergency department
      patients.
AB  - Inaccuracies in self-reports may lead to duplication of therapy, failure to
      appreciate non-compliance leading to exacerbation of chronic medical conditions,
      or inaccurate research conclusions. Our objective is to determine the accuracy of
      self-reported drug ingestion histories in patients presenting to an urban
      academic emergency department (ED). We conducted a prospective cohort study in ED
      patients presenting for pain or nausea. We obtained a structured drug ingestion
      history including all prescription drugs, over-the-counter medication (OTC)
      drugs, and illicit drugs for the 48 hours prior to ED presentation. We obtained
      urine comprehensive drug screens (CDS) and determined self-report/CDS
      concordance. Fifty-five patients were enrolled. Self-reported drug ingestion
      histories were poor in these patients; only 17 (30.9%) of histories were
      concordant with the CDS. For the individual drug classes, prescription drug-CDS
      was concordant in 32 (58.2%), OTC-CDS was concordant in 33 (60%), and illicit
      drug-CDS was concordant in 45 (81.8%) of subjects. No demographic factors
      predicted an accurate self-reported drug history. Sixteen patients had drugs
      detected by CDS that were unreported by history. Nine of these 16 included an
      unreported opioid. In conclusion, self-reported drug ingestion histories are
      often inaccurate and resources are needed to confirm compliance and ensure
      unreported drugs are not overlooked. 

PMID- 25052327
TI  - Reduced riparian zone width compromises aquatic macroinvertebrate communities in
      streams of southern Brazil.
AB  - Recent changes in Brazilian legislation reduced the width of riparian forest
      buffer needed to be preserved in private properties from 30 to 15 m or less. The
      consequences of these modifications can be dramatic, mainly because riparian
      buffer width is an important parameter for riparian forest structure and
      functioning. Our study assessed whether (1) macroinvertebrate family richness and
      Ephemeroptera, Plecoptera, and Trichoptera (EPT) family richness decrease with
      reduced riparian buffer width; (2) taxonomic composition and functional feeding
      group (FFG) composition of macroinvertebrates vary with a reduced riparian buffer
      width; and (3) reduced riparian buffer width similarly influence the
      macroinvertebrate community in different stream substrates. We selected three
      fragments with different riparian buffer widths (>40, <30, and <15 m) in three
      streams (fourth and fifth orders) in the Sinos River watershed, southern Brazil.
      Our results show that on all substrate types, reducing the width of the riparian
      buffer altered neither the macroinvertebrate richness nor EPT richness. However,
      EPT richness was greater in the substrates stone and gravel than leaf litter,
      independent of riparian buffer width. There was a significant difference in
      macroinvertebrate composition among riparian buffer widths. The macroinvertebrate
      composition and FFG differed among substrates, independent of riparian buffer
      width. This study showed that riparian buffer widths <15 m altered the
      macroinvertebrate community. A width greater than 15 m is necessary to maintain
      the composition and trophic conditions of macroinvertebrate families similar to
      those found in reference states of conservation. 

PMID- 25052328
TI  - Regional status assessment of stony corals in the US Virgin Islands.
AB  - States may protect coral reefs using biological water quality standards outlined
      by the Clean Water Act. This requires biological assessments with indicators
      sensitive to human disturbance and regional, probability-based survey designs.
      Stony coral condition was characterized on a regional scale for the first time in
      the nearshore waters of the US Virgin Islands (USVI). Coral composition,
      abundance, size, and health were assessed at 66 stations in the St. Croix region
      in fall 2007 and at 63 stations in the St. Thomas and St. John region in winter
      2009. Indicators were chosen for their sensitivity to human disturbance. Both
      surveys were probability-based (random) designs with station locations
      preselected from areas covered by hardbottom and coral reef substrate. Taxa
      richness was as high as 21 species but more than half the area of both regions
      exhibited taxa richness of <10 species in the 25 m(2) transect area. Coral
      density was as high as 5 colonies m(-2) but more than half the area of both
      regions had <2 colonies m(-2). Both regions showed similar dominant species based
      on frequency of occurrence and relative abundance. Because of large colony sizes,
      Montastrea annularis provided more total surface area and live surface area than
      more abundant species. The surveys establish baseline regional conditions and
      provide a foundation for long-term regional monitoring envisioned by the USVI
      Department of Planning and Natural Resources. The probabilistic sampling design
      assures the data can be used in Clean Water Act reporting. 

PMID- 25052329
TI  - Assessment of imidacloprid degradation by soil-isolated Bacillus
      alkalinitrilicus.
AB  - Imidacloprid is extensively used on a broad range of crops worldwide as seed
      dressing, soil treatment, and foliar application. Hence, the degradation
      potential of bacterial strains from sugarcane-growing soils was studied in liquid
      medium for subsequent use in bioremediation of contaminated soils. The microbe
      cultures degrading imidacloprid were isolated and enriched on Dorn's broth
      containing imidacloprid as sole carbon source maintained at 28  degrees C and
      Bacillus alkalinitrilicus showed maximum potential to degrade imidacloprid. Clay
      loam soil samples were fortified with imidacloprid at 50, 100, and 150 mg kg(-1)
      along with 45 * 10(7) microbe cells under two opposing sets of conditions, viz.,
      autoclaved and unautoclaved. To study degradation and metabolism of imidacloprid
      under these two conditions, samples were drawn at regular intervals of 7, 14, 28,
      35, 42, 49, and 56 days. Among metabolites, three metabolites were detected,
      viz., 6-chloronicotinic acid, nitrosimine followed by imidacloprid-NTG under both
      the conditions. Total imidacloprid residues were not found to follow the first
      order kinetics in both types of conditions. This paper reports for the first time
      the potential use of pure cultures of soil-isolated native bacterium B.
      alkalinitrilicus and also its use along with natural soil microflora for
      remediation of imidacloprid-contaminated soils. 

PMID- 25052330
TI  - GC estimation of organic hydrocarbons that threaten shallow Quaternary sandy
      aquifer Northwestern Gulf of Suez, Egypt.
AB  - Soil and groundwater contamination is one of the important environmental problems
      at petroleum-related sites, which causes critical environmental and health
      defects. Severe petroleum hydrocarbon contamination from coastal refinery plant
      was detected in a shallow Quaternary sandy aquifer is bordered by Gulf in the
      Northwestern Gulf of Suez, Egypt. The overall objective of this investigation is
      to estimate the organic hydrocarbons in shallow sandy aquifers, released from
      continuous major point-source of pollution over a long period of time (91 years
      ago). This oil refinery contamination resulted mainly in the improper disposal of
      hydrocarbons and produced water releases caused by equipment failures, vandalism,
      and accidents that caused direct groundwater pollution or discharge into the
      gulf. In order to determine the fate of hydrocarbons, detailed field
      investigations were made to provide intensive deep profile information. Eight
      composite randomly sediment samples from a test plot were selected for
      demonstration. The tested plot was 50 m long * 50 m wide * 70 cm deep. Sediment
      samples were collected using an American auger around the point 29 degrees  57'
      33" N and 32 degrees  30' 40" E in 2012 and covered an area of 2,500 m(2) which
      represents nearly 1/15 of total plant area (the total area of the plant is
      approximately 3.250 km(2)). The detected total petroleum hydrocarbons (TPHs) were
      2.44, 2.62, 4.54, 4.78, 2.83, 3.22, 2.56, and 3.13 wt%, respectively. TPH was
      calculated by differences in weight and subjected to gas chromatography (GC).
      Hydrocarbons were analyzed on Hewlett-Packard (HP-7890 plus) gas chromatograph
      equipped with a flame ionization detector (FID). The percentage of paraffine of
      the investigated TPH samples was 7.33, 7.24, 7.58, 8.25, 10.25, 9.89, 14.77, and
      17.53 wt%, respectively. 

PMID- 25052331
TI  - Markers of hepatitis delta virus infection can be detected in follicular fluid
      and semen.
AB  - BACKGROUND: Hepatitis delta virus (HDV) is a satellite of HBV and needs this
      latter's envelope for its morphogenesis and propagation. An estimated 5-20% of
      HBV-infected patients are also infected with HDV. No studies have ever been
      performed to determine the presence of HDV in follicular fluid (FF) and semen of
      HDV-infected patients. OBJECTIVES: To investigate the presence of HDV markers in
      the FF or in the semen of two HDV-infected patients. DESIGN: Two unrelated HDV
      infected patients, a woman and a man pursuing in vitro fertilization (IVF),
      participated in this study. FF was collected after analysis of oocyte retrieval.
      The supernatant of seminal plasma (SP) and the final pellet (FP) were
      fractionated from freshly ejaculated semen. Serological and molecular markers of
      HDV infection were searched for in these different samples. RESULTS: The woman
      was infected with an HDV-7 genotype strain and her HDV plasma viral load (VL) was
      6 log copies/mL. HDV antibodies and RNA were also detected in the FF, however the
      RNA VL value there was lower by more than 4 log. The man was infected with an HDV
      1 strain and his plasma VL was 6.7 log copies/mL. Total anti-HDV antibodies were
      positive in the serum, in the SP and in the FP, while IgM were detected only in
      the serum. However, HDV RNA was negative in the SP and in the FP. CONCLUSION: HDV
      markers can be found in the follicular fluid or in the semen of infected
      patients.

PMID- 25052332
TI  - Immunohistochemistry analysis of pulmonary infiltrates in necropsy samples of
      children with non-pandemic lethal respiratory infections (RSV; ADV; PIV1; PIV2;
      PIV3; FLU A; FLU B).
AB  - BACKGROUND: Acute viral respiratory infections represent a globally important
      cause of morbidity and mortality in childhood. An individual's cellular response
      appears to play a critical role in recovery from infections, given that
      individuals with impaired cellular immunity, congenital or acquired, have more
      severe diseases and secrete the virus for longer periods. OBJECTIVES: The aim of
      this study was to immunohistochemically evaluate the expression of the cell
      surface antigens CD4, CD8, CD25, CD14 and CD74, in pneumonic infiltrates in the
      alveolar septa using paraffin-embedded lung samples from autopsies of
      immunocompetent children who died of lethal, non-pandemic, severe acute
      respiratory infections. STUDY DESIGN: From 794 cases of pediatric autopsies of
      patients with severe respiratory disease (between 1960 and 2004), 193 cases were
      selected for this study. To identify subpopulations of inflammatory cells in the
      alveolar septa, cell surface antigen expression was assessed by
      immunohistochemistry using the following primary antibodies: anti-CD4, anti-CD8,
      anti-CD14, anti-CD25 and anti-CD74. RESULTS: The TCD8+ lymphocyte count was
      higher in the virus-positive group (p = 0.04) and was also much higher among
      cases that were positive for more than three viral types (p = 0.016). There were
      fewer CD14+ cells in cases of AdV (adenovirus) infection (p = 0.002), and there
      was a predominance of CD74+ cells in the histopathological pattern defined as
      interstitial pneumonitis (p = 0.037). CONCLUSIONS: The results of this study
      demonstrate that TCD8+ lymphocytes present in the alveolar septa participate to a
      greater extent in the response toward viral pneumonia, while CD14+ cell numbers
      are often reduced in cases of AdV.

PMID- 25052333
TI  - RNA-binding proteins associated molecular mechanisms of motor neuron degeneration
      pathogenesis.
AB  - Motor neuron diseases are neurodegenerative disorders that trigger motor neurons
      to degenerate and lead to paralysis. Our understanding on the mechanisms of motor
      neuron degeneration has been enhanced by recent cellular and molecular
      researches. In this review, I highlight advances in RNA-binding proteins
      associated molecular mechanisms of motor neuron degeneration pathogenesis
      including ribonucleoprotein-associated motor neuron degeneration which is focused
      on RNA-binding protein aggregation associated aberrant RNA metabolism and stress
      granules mediated translational repression, neurofilament associated aggregate
      formation, and prion protein associated accumulation of misfolded proteins.
      Progress overviewed above will be valuable to the development of more targeted
      diagnostic tests and therapies. 

PMID- 25052334
TI  - Nicotine patch preloading for smoking cessation (the preloading trial): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: The use of nicotine replacement therapy before quitting smoking is
      called nicotine preloading. Standard smoking cessation protocols suggest
      commencing nicotine replacement therapy only on the first day of quitting smoking
      (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more
      successful smoking cessation pharmacotherapies are used prior to the quit day as
      well as after. Nicotine preloading could improve quit rates by reducing
      satisfaction from smoking prior to quitting and breaking the association between
      smoking and reward. A systematic literature review suggests that evidence for the
      effectiveness of preloading is inconclusive and further trials are needed.
      METHODS/DESIGN: This is a study protocol for a multicenter, non-blinded,
      randomized controlled trial based in the United Kingdom, enrolling 1786 smokers
      who want to quit, funded by the National Institute for Health Research, Health
      Technology Assessment program, and sponsored by the University of Oxford.
      Participants will primarily be recruited through general practices and smoking
      cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or
      not, for four weeks before quitting, whilst smoking as normal. All participants
      will be referred to receive standard smoking cessation service support. Follow
      ups will take place at one week, four weeks, six months and 12 months after quit
      day. The primary outcome will be prolonged, biochemically verified six-month
      abstinence. Additional outcomes will include point prevalence abstinence and
      abstinence of four-week and 12-month duration, side effects, costs of treatment,
      and markers of potential mediators and moderators of the preloading effect.
      DISCUSSION: This large trial will add substantially to evidence on the
      effectiveness of nicotine preloading, but also on its cost effectiveness and
      potential mediators, which have not been investigated in detail previously. A
      range of recruitment strategies have been considered to try and compensate for
      any challenges encountered in recruiting the large sample, and the multicentre
      design means that knowledge can be shared between recruitment teams. The
      pragmatic study design means that results will give a realistic estimate of the
      success of the intervention if it were to be rolled out as part of standard
      smoking cessation service practice. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN33031001. Registered 27 April 2012.

PMID- 25052335
TI  - Incorporation of aurochs into a cattle herd in Neolithic Europe: single event or
      breeding?
AB  - Domestication is an ongoing process continuously changing the lives of animals
      and humans and the environment. For the majority of European cattle (Bos taurus)
      genetic and archaeozoological evidence support initial domestication ca. 11'000
      BP in the Near East from few founder aurochs (Bos primigenius) belonging to the
      mitochondrial DNA T macro-haplogroup. Gene flow between wild European aurochs of
      P haplogroup and domestic cattle of T haplogroup, coexisting over thousands of
      years, appears to have been sporadic. We report archaeozoological and ancient DNA
      evidence for the incorporation of wild stock into a domestic cattle herd from a
      Neolithic lake-dwelling in Switzerland. A complete metacarpus of a small and
      compact adult bovid is morphologically and genetically a female. With withers
      height of ca. 112 cm, it is comparable in size with small domestic cattle from
      contemporaneous sites in the area. The bone is directly dated to 3360-3090 cal BC
      and associated to the Horgen culture, a period of the secondary products
      revolution. The cow possessed a novel mtDNA P haplotype variant of the European
      aurochs. We argue this is either a single event or, based on osteological
      characteristics of the Horgen cattle, a rare instance of intentional breeding
      with female aurochs.

PMID- 25052336
TI  - Trifluoromethylation of arenediazonium salts with fluoroform-derived CuCF3 in
      aqueous media.
AB  - A new protocol has been developed for trifluoromethylation of arenediazonium
      salts with moisture-sensitive CuCF3 (from fluoroform) in aqueous media. The
      reaction is governed by a radical mechanism, tolerates a broad variety of
      functional groups, and is applicable to the synthesis of complex,
      polyfunctionalized molecules. 

PMID- 25052337
TI  - Life cycle assessment of thermal waste-to-energy technologies: review and
      recommendations.
AB  - Life cycle assessment (LCA) has been used extensively within the recent decade to
      evaluate the environmental performance of thermal Waste-to-Energy (WtE)
      technologies: incineration, co-combustion, pyrolysis and gasification. A critical
      review was carried out involving 250 individual case-studies published in 136
      peer-reviewed journal articles within 1995 and 2013. The studies were evaluated
      with respect to critical aspects such as: (i) goal and scope definitions (e.g.
      functional units, system boundaries, temporal and geographic scopes), (ii)
      detailed technology parameters (e.g. related to waste composition, technology,
      gas cleaning, energy recovery, residue management, and inventory data), and (iii)
      modeling principles (e.g. energy/mass calculation principles, energy
      substitution, inclusion of capital goods and uncertainty evaluation). Very few of
      the published studies provided full and transparent descriptions of all these
      aspects, in many cases preventing an evaluation of the validity of results, and
      limiting applicability of data and results in other contexts. The review clearly
      suggests that the quality of LCA studies of WtE technologies and systems
      including energy recovery can be significantly improved. Based on the review, a
      detailed overview of assumptions and modeling choices in existing literature is
      provided in conjunction with practical recommendations for state-of-the-art LCA
      of Waste-to-Energy. 

PMID- 25052338
TI  - Comparative analysis of anaerobically digested wastes flow properties.
AB  - The flow curve of anaerobically digested wastes from different origins was
      determined through rheological measurements. Regardless of their origin, samples
      can be divided into two families: simple non-Newtonian liquids well modelled by
      basic power law below 10%DC and viscoelastic liquids with a yield stress, well
      modelled by a Herschel-Bulkley model above. In all the cases, the rheological
      behaviour is driven by both the organic content and the volatile fraction
      (organic content/solid content), indicating that anaerobic digestion tends to
      smooth the rheological characteristics of organic wastes, whichever their
      origins. 

PMID- 25052339
TI  - Full-scale blending treatment of fresh MSWI leachate with municipal wastewater in
      a wastewater treatment plant.
AB  - Fresh leachate, generated in municipal solid waste incineration (MSWI) plants,
      contains various pollutants with extremely high strength organics, which usually
      requires expensive and complex treatment processes. This study investigated the
      feasibility of blending treatment of MSWI leachate with municipal wastewater.
      Fresh MSWI leachate was pretreated by coagulation-flocculation with FeCl3 2 g/L
      and CaO 25 g/L, plate-and-frame filter press, followed by ammonia stripping at pH
      above 12. After that, blending treatment was carried out in a full-scale
      municipal wastewater treatment plant (WWTP) for approximately 3 months. Different
      operational modes consisting of different pretreated leachate and methanol
      addition levels were tested, and their performances were evaluated. Results
      showed that throughout the experimental period, monitored parameters in the WWTP
      effluent, including COD (<60 mg/L), BOD5 (<20 mg/L), ammonium (<8 mg/L),
      phosphorus (<1.5 mg/L) and heavy metals, generally complied with the Chinese
      sewage discharged standard. Under the experimental conditions, a certain amount
      of methanol was needed to fulfill TN removal. An estimation of the operation cost
      revealed that the expenditure of blending treatment was much lower than the total
      costs of respective treatment of MSWI leachate and municipal wastewater. The
      outcomes indicated that blending treatment could not only improve the
      treatability of the MSWI leachate, but also reduce the treatment cost of the two
      different wastewaters.

PMID- 25052340
TI  - Generation of copper rich metallic phases from waste printed circuit boards.
AB  - The rapid consumption and obsolescence of electronics have resulted in e-waste
      being one of the fastest growing waste streams worldwide. Printed circuit boards
      (PCBs) are among the most complex e-waste, containing significant quantities of
      hazardous and toxic materials leading to high levels of pollution if landfilled
      or processed inappropriately. However, PCBs are also an important resource of
      metals including copper, tin, lead and precious metals; their recycling is
      appealing especially as the concentration of these metals in PCBs is considerably
      higher than in their ores. This article is focused on a novel approach to recover
      copper rich phases from waste PCBs. Crushed PCBs were heat treated at 1150
      degrees C under argon gas flowing at 1L/min into a horizontal tube furnace.
      Samples were placed into an alumina crucible and positioned in the cold zone of
      the furnace for 5 min to avoid thermal shock, and then pushed into the hot zone,
      with specimens exposed to high temperatures for 10 and 20 min. After treatment,
      residues were pulled back to the cold zone and kept there for 5 min to avoid
      thermal cracking and re-oxidation. This process resulted in the generation of a
      metallic phase in the form of droplets and a carbonaceous residue. The metallic
      phase was formed of copper-rich red droplets and tin-rich white droplets along
      with the presence of several precious metals. The carbonaceous residue was found
      to consist of slag and ~30% carbon. The process conditions led to the segregation
      of hazardous lead and tin clusters in the metallic phase. The heat treatment
      temperature was chosen to be above the melting point of copper; molten copper
      helped to concentrate metallic constituents and their separation from the
      carbonaceous residue and the slag. Inert atmosphere prevented the re-oxidation of
      metals and the loss of carbon in the gaseous fraction. Recycling e-waste is
      expected to lead to enhanced metal recovery, conserving natural resources and
      providing an environmentally sustainable solution to the management of waste
      products.

PMID- 25052341
TI  - Cerebral Infarction due to Central Vein Occlusion in a Hemodialysis Patient.
AB  - Venous congestive encephalopathy is a rare complication of central venous
      occlusion in hemodialysis patients with upper extremity dialysis created shunts.
      We describe the clinical presentation and endovascular management of an end-stage
      renal disease patient with a left upper extremity arteriovenous graft who
      developed intracranial venous hypertension, left-sided subdural and subarachnoid
      intracranial hemorrhage, and left-sided cerebral infarcts related to a left
      brachiocephalic vein occlusion. 

PMID- 25052342
TI  - Impaired decision-making and selective cortical frontal thinning in Cushing's
      syndrome.
AB  - CONTEXT AND OBJECTIVE: Cushing's syndrome (CS) is caused by a glucocorticoid
      excess. This hypercortisolism can damage the prefrontal cortex, known to be
      important in decision-making. Our aim was to evaluate decision-making in CS and
      to explore cortical thickness. SUBJECTS AND METHODS: Thirty-five patients with CS
      (27 cured, eight medically treated) and thirty-five matched controls were
      evaluated using Iowa gambling task (IGT) and 3 Tesla magnetic resonance imaging
      (MRI) to assess cortical thickness. The IGT evaluates decision-making, including
      strategy and learning during the test. Cortical thickness was determined on MRI
      using freesurfer software tools, including a whole-brain analysis. RESULTS: There
      were no differences between medically treated and cured CS patients. They
      presented an altered decision-making strategy compared to controls, choosing a
      lower number of the safer cards (P < 0.05). They showed more difficulties than
      controls to learn the correct profiles of wins and losses for each card group (P
      < 0.05). In whole-brain analysis, patients with CS showed decreased cortical
      thickness in the left superior frontal cortex, left precentral cortex, left
      insular cortex, left and right rostral anterior cingulate cortex, and right
      caudal middle frontal cortex compared to controls (P < 0.001). CONCLUSIONS:
      Patients with CS failed to learn advantageous strategies and their behaviour was
      driven by short-term reward and long-term punishment, indicating learning
      problems because they did not use previous experience as a feedback factor to
      regulate their choices. These alterations in decision-making and the decreased
      cortical thickness in frontal areas suggest that chronic hypercortisolism
      promotes brain changes which are not completely reversible after endocrine
      remission.

PMID- 25052343
TI  - Think like a plant.

PMID- 25052344
TI  - Capacitive measurement of ECG for ubiquitous healthcare.
AB  - The technology for measuring ECG using capacitive electrodes and its applications
      are reviewed. Capacitive electrodes are built with a high-input-impedance
      preamplifier and a shield on their rear side. Guarding and driving ground are
      used to reduce noise. An analysis of the intrinsic noise shows that the thermal
      noise caused by the resistance in the preamplifier is the dominant factor of the
      intrinsic noise. A fully non-contact capacitive measurement has been developed
      using capacitive grounding and applied to a non-intrusive ECG measurement in
      daily life. Many ongoing studies are examining how to enhance the quality and
      ease of applying electrodes, thus extending their applications in ubiquitous
      healthcare from attached-on-object measurements to wearable or EEG measurements. 

PMID- 25052345
TI  - Impact of surveillance of hepatitis b and hepatitis c in patients with
      inflammatory bowel disease under anti-TNF therapies: multicenter prospective
      observational study (REPENTINA 3).
AB  - AIMS: Assess IBD patients starting anti-TNF for the impact of preventive measures
      in HBV and/or HCV, and the predictive response factors to HBV vaccination.
      METHODS: Multicenter prospective study including 389 IBD patients. Four
      interventions were established: I-1) anti-HBs <100IU/L: HBV vaccination with
      double doses at 0-1-2months, and revaccination if titres <100IU/L (seroprotection
      defined as anti-HBs10-100IU/L and effective vaccination anti-HBs >100IU/L); I-2)
      anti-HBs >100IU/L (previous effective vaccination): monitoring levels; I-3) anti
      HBc and/or HCV+: analysis every two months; I-4) HBsAg+: start anti-virals.
      RESULTS: I-1 and I-2) For first vaccination, effective vaccination and
      seroprotection were obtained in 26.4% and 43.5%, and for revaccination 31.3% and
      44.4%, respectively. Predictive factors of effective vaccination were age
      <=30years (OR=2.2) and being vaccinated simultaneously with anti-TNF (OR=5.2)
      instead of late vaccination, whereas age <=30years (OR=2.6) and anti-TNF
      monotherapy (OR=2.4) were predictive for seroprotection. 80.8% of patients
      previously vaccinated maintained titres at 29months follow-up. The only factor
      related to maintaining titres was previous vaccination versus achieving effective
      vaccination during anti-TNF (HR=2.49); I-3 and I-4) HBV-DNA + without
      reactivation was detected in 7% of 29 anti-HBc. No reactivation was found in the
      remaining HCV (n=5) or HBsAg (n=4) patients. CONCLUSIONS: 1) Response to
      vaccination/revaccination is low in patients with anti-TNF. Young patients
      vaccinated at the beginning of anti-TNF and receiving it as a monotheraphy showed
      better response. 2) Long-lasting effective vaccination is greatest in patients
      previously vaccinated. 3) Following-up the established surveillance and/or
      preventive anti-viral therapy seems to be safe in HBV and HCV patients.

PMID- 25052346
TI  - In vitro sensitivity assays and clinical response to glucocorticoids in patients
      with inflammatory bowel disease.
AB  - BACKGROUND: Glucocorticoids (GCs) are steroid hormones used to induce remission
      in moderate-to-severe inflammatory bowel disease (IBD). A substantial fraction of
      patients do not respond to GC treatment and require alternate therapies or
      surgery. At present, non-response can only be assessed empirically by observing
      continued disease activity. METHODS: To identify potential biomarkers of GC
      response, we retrospectively identified and recruited 18 GC-responsive and 18 GC
      nonresponsive IBD patients. This sample included 14 patients with ulcerative
      colitis (UC) and 22 patients with Crohn's disease (CD), all previously treated
      with steroids. In peripheral blood mononuclear cells from each patient, we
      performed in vitro assays to measure GC inhibition of three different immune
      stimulants (phytohemagglutinin [PHA], alpha-CD3/alpha-CD28, and
      lipopolysaccharide [LPS]). RESULTS: In both diseases, we found that inhibition of
      PHA-mediated T cell proliferation was significantly associated with clinical GC
      response (P=0.04). Inhibition of proliferation due to direct T cell receptor
      stimulation using alpha-CD3/alpha-CD28 was also significantly associated with
      clinical GC response in UC patients (P=0.009), but not in CD patients (P=0.78).
      Interestingly, inhibition of LPS-mediated cytokine secretion showed the strongest
      association with clinical GC response across both diseases (P=0.005).
      CONCLUSIONS: We show that inhibition of LPS stimulation is more strongly
      associated with clinical GC response in IBD patients than inhibition of PHA and
      alpha-CD3/alpha-CD28-mediated proliferation. These results support an important
      role of bacterial recognition and innate immunity in the etiology of IBD. This
      assay could be a powerful predictor of clinical response to GCs.

PMID- 25052347
TI  - Does fecal calprotectin predict short-term relapse after stopping TNFalpha
      blocking agents in inflammatory bowel disease patients in deep remission?
AB  - BACKGROUND AND AIMS: This prospective multicenter study examined whether elevated
      fecal calprotec tin (FC) concentrations after stopping TNFalpha-blocking therapy
      can predict clinical or endoscopic relapse. In addition, we evaluated the impact
      of histological remission on the relapse risk. METHODS: We enrolled inflammatory
      bowel disease (IBD) patients who were in clinical, endoscopic, and FC-based (<
      100 MUg/g) remission after a minimum 11 months of TNFalpha-blocking therapy. The
      patients were followed-up for 12 months after the discontinuation of TNFalpha
      blocking therapy. FC was collected monthly for the first 6 months and thereafter
      every second month. Ileocolonoscopy was performed at inclusion, at 4 months, at
      the study end, and at the time of clinical relapse. RESULTS: Of 52 enrolled
      patients, 49 (16 Crohn's disease, 33 ulcerative colitis/IBD unclassified)
      provided the stool samples requested and comprised the study group. During the
      follow-up, 15/49 (31%) relapsed, whereas 34 (69%) remained in remission. Patients
      relapsing showed constantly elevated FC levels for a median of 94 (13-317) days
      before the relapse. Significant increase in median FC levels was seen 2 (p =
      0.0014), 4 (p = 0.0056), and 6 (p = 0.0029) months before endoscopic relapse.
      Constantly normal FC concentrations during the follow-up were highly predictive
      for clinical and endoscopic remission. Normal FC concentrations in patients with
      remission were associated with histological remission. CONCLUSION: FC seems to
      increase and remain elevated before clinical or endoscopic relapse, suggesting
      that it can be used as a surrogate marker for predicting and identifying patients
      requiring close follow-up in clinical practice.

PMID- 25052348
TI  - Cold tolerance of the maize orange leafhopper, Cicadulina bipunctata.
AB  - Cicadulina bipunctata was originally distributed in tropical and subtropical
      regions of the Old World. This leafhopper recently expanded its distribution area
      to southern parts of temperate Japan. In this study, factors affecting the
      overwintering ability of C. bipunctata were examined. A series of laboratory
      experiments revealed that cold acclimation at 15 degrees C for 7days enhanced the
      cold tolerance of C. bipunctata to the same level as an overwintering population,
      adult females were more tolerant of cold temperature than adult males, and
      survival of acclimated adult females was highly dependent on temperature from -5
      to 5 degrees C and exposure duration to the temperature. The temperature of
      crystallization of adult females was approximately -19 degrees C but temperatures
      in southern temperate Japan rarely dropped below -10 degrees C in the winter,
      indicating that overwintering C. bipunctata adults in temperate Japan are not
      killed by freezing injury but by indirect chilling injury caused by long-term
      exposure to moderately low temperatures. An overwintering generation of C.
      bipunctata had extremely low overwinter survival (<1%) in temperate Japan;
      however, based on winter temperature ranges, there are additional areas amenable
      to expansion of C. bipunctata in temperate Japan. 

PMID- 25052349
TI  - Brevican knockdown reduces late-stage glioma tumor aggressiveness.
AB  - Growing evidence supports the important role of the tumor microenvironment (TME)
      in cancer biology. A defining aspect of the glioma TME is the unique composition
      and structure of its extracellular matrix (ECM), which enables tumor cells to
      overcome the inhibitory barriers of the adult central nervous system (CNS). In
      this way, the TME plays a role in glioma invasion and the cellular heterogeneity
      that distinguishes these tumors. Brain Enriched Hyaluronan Binding
      (BEHAB)/brevican (B/b), is a CNS-specific ECM constituent and is upregulated in
      the glioma TME. Previous studies have shown B/b exerts a pro-invasive function,
      suggesting it may represent a target to reduce glioma pathogenesis. Herein, we
      also provide evidence that B/b expression is enriched in the glioma initiating
      cell (GIC) niche. We demonstrate that B/b plays roles in the pathological
      progression, aggressiveness, and lethality of tumors derived from human GICs and
      traditional glioma cell lines. Interestingly, we found that B/b is not required
      to maintain the defining phenotypic properties of GICs and thereby acts primarily
      in late stages of glioma progression. This study suggests that the increased
      expression of B/b in the TME is a valuable therapeutic target for glioma.

PMID- 25052350
TI  - Prognostic stratification of brain metastases from hepatocellular carcinoma.
AB  - The aim of this study is to evaluate prognostic factors of brain metastases from
      hepatocellular carcinoma. Medical records of 95 patients who have been diagnosed
      of brain metastases from hepatocellular carcinoma between January 2000 and
      December 2011 were retrospectively reviewed. The median age at diagnosis of brain
      metastases is 56.1 years. Eighty-two patients were male. Median interval from
      diagnosis of hepatocellular carcinoma to brain metastases was 29.5 months. Eighty
      eight patents had extracranial metastases, and the lung was the most frequent
      involved organ. Motor weakness was the most frequent presenting symptom (49.5%).
      Intracranial hemorrhage was present in 71 patients (74.7%). Brain metastases were
      treated with whole brain radiation therapy (WBRT) alone in 57 patients,
      radiosurgery alone in 18, surgery and WBRT in 6, surgery and radiosurgery in 3,
      surgery alone in 3, radiosurgery and WBRT in 2, and conservative management only
      in 6. Median overall survival was 3.0 months. Multivariate analysis showed ECOG
      performance status, Child-Pugh class, AFP level, number of brain lesions, and
      treatment modality were associated with survival (p < 0.05). When patients were
      stratified with four prognostic factors including ECOG performance status, Child
      Pugh class, AFP level, and number of brain lesions, median survival time for
      patients with 0-1, 2, 3-4 risk factors were 5.8 months, 2.5 months and 0.6
      months, respectively (p < 0.001). In conclusion, we can estimate the survival of
      patients by prognostic stratification, although overall prognosis of patients
      with brain metastases from hepatocellular carcinoma is poor.

PMID- 25052351
TI  - [Chronic renal insufficiency following childhood cancer].
AB  - Modern intensive treatment modalities have led to an increasing number of
      survivors of childhood cancer, who are at risk for developing long-term sequelae.
      Since decline of renal function can develop subclinically, adequate surveillance
      is required for survivors previously treated with nephrotoxic treatment
      modalities. We describe a 34-year-old man, who had been treated for
      nephroblastoma (stage I) at the age of 5 years and who regularly visited the
      adult late-effects clinic for survivors of childhood cancer. Twenty years after
      his treatment for nephroblastoma glomerular function started to decline and
      progressive chronic kidney disease (CKD) stage 3 developed. It is important to
      recognise that survivors of childhood cancer can be at risk of developing long
      term effects, including impaired renal function. Apart from regular surveillance
      by expert medical specialists dedicated to childhood cancer survivor care, more
      intensive communication with primary health care physicians is necessary to
      improve awareness of these issues in the growing cohort of childhood cancer
      survivors. 

PMID- 25052352
TI  - [Haemoglobinopathy in the 21st century: incidence, diagnosis and heel prick
      screening].
AB  - OBJECTIVE: To determine the incidence of severe haemoglobinopathy, to evaluate
      the effect of heel prick screening, and to identify those children who do not
      benefit from this early diagnosis. DESIGN: Prospective descriptive study. METHOD:
      Registration of all symptomatic and asymptomatic children who between 2003-2009
      were newly diagnosed with the a severe form of a hereditary disorder concerning
      the formation of the alpha haemoglobin chain (HbH disease), or the beta
      haemoglobin chain (sickle cell disease or beta thalassaemia major) in the
      Netherlands. Registration was done by collecting anonymised reports from the
      Dutch Paediatric Surveillance Unit and TNO, and by additional questionnaires.
      RESULTS: During the study period, 48 children (range: 36-76) per year were
      diagnosed with severe haemoglobinopathy. The overall incidence was 2.5 per 10,000
      live births. The incidence of sickle cell disease diagnosed by heel prick
      screening was 2.1 per 10,000 live births and of thalassaemia major 0.6 per 10,000
      live births. In 7% of the children with sickle cell disease who were diagnosed
      without any form of screening, the diagnosis was made on (a life threatening)
      infection. Twenty-two percent of the children with a severe form of
      haemoglobinopathy were not born in the Netherlands. The parents of almost half of
      the children with sickle cell disease originally came from West- or Central
      Africa. The parents of children with thalassaemia major were mainly from Morocco
      or various Asiatic countries. CONCLUSION: The number of children with severe
      haemoglobinopathy in the Netherlands has trebled since 1992. In order for all
      children to benefit from early diagnosis and preventive treatment, it is
      advisable that children who originate from risk areas should be tested for
      haemoglobinopathy when they first arrive in the Netherlands.

PMID- 25052353
TI  - [Pigtail stent for gallbladder drainage].
AB  - Endoscopic transpapillary gallbladder drainage is a new, relatively non-invasive
      treatment for patients with symptomatic gallbladder disease and a high surgery
      risk. Placement of an internal pigtail stent is an alternative treatment for
      percutaneous gallbladder drainage. This procedure can be performed in patients
      with a temporary contra-indication - in preparatory process to a cholecystectomy 
      as well as in patients with a prolonged contra-indication where the pigtail
      stent can remain in situ for a longer period of time. This technique appears to
      be an effective and safe procedure for patients with acute cholecystitis or
      symptomatic gallbladder disease and a high surgery risk. 

PMID- 25052354
TI  - [Rectal bleeding after radiotherapy for prostate cancer].
AB  - This clinical lesson, based on two case histories, illustrates a complication
      seen after manipulation of the rectal wall in patients who have undergone
      radiotherapy for localised prostate cancer. Rectal bleeding, which is feared by
      patients, can be the first sign of radiation proctitis. Manipulation of the
      rectal wall, for example by taking biopsies or Argon plasma coagulation, should
      be done with caution and only if absolutely necessary, because it can lead to
      fistula formation. 

PMID- 25052355
TI  - [The professional interpreter disappears: quality is jeopardized].
AB  - According to Dutch law, patients have the right to comprehensible communication.
      However, professional interpreters are not being used sufficiently: health care
      providers often do not recognize when language barriers interfere with
      comprehension. The use of professional interpreters declined even further when
      the Dutch government withdrew its funding for medical interpreters in January
      2012. Additionally, the government's stance that non-native speakers have to
      master the language and organize translating help when needed seems to have given
      a signal to health care providers that this is not their responsibility.
      Nonetheless, health care providers are obliged by law to provide comprehensible
      information. Therefore, it is important to provide proper training so they can
      recognize language barriers and know when a professional interpreter is
      necessary. In addition, a financial aid system needs to be developed for those
      patients who cannot reasonably be expected to have mastered the language. 

PMID- 25052356
TI  - [Systemic sclerosis: a multisystem disease].
AB  - Systemic sclerosis is a rare, systemic autoimmune disease, characterized by
      inflammation, vasculopathy and fibrosis of the skin and internal organs. The
      disease is associated with a significantly increased morbidity and mortality, and
      can be rapidly progressive. Interstitial lung disease, renal hypertensive crisis,
      cardiac involvement and pulmonary arterial hypertension are life-threatening
      complications. Early treatment with immunosuppressive drugs can prevent
      progression and decrease morbidity and mortality. 

PMID- 25052357
TI  - [An ill woman with persisting globus].
AB  - We report a 56-year-old woman with a migrating foreign body in the digestive
      tract, eventually located at the prevertebral space. The foreign body was missed
      during outpatient flexible endoscopy. Most important complication is
      mediastinitis, clinically presenting as malaise, fever and pain between the
      scapulae. 

PMID- 25052358
TI  - [A woman with purple-red nodules in an oedematous arm].
AB  - A woman with postmastectomy lymphoedema presented with purple-red nodules on the
      right upper arm. Histopathology of a skin biopsy showed a cutaneous angiosarcoma.
      Angiosarcoma arising in an oedematous arm is called the Stewart-Treves syndrome
      and is a rare and late complication of breast cancer treatment. 

PMID- 25052359
TI  - The use of Thompson sampling to increase estimation precision.
AB  - In this article, we consider a sequential sampling scheme for efficient
      estimation of the difference between the means of two independent treatments when
      the population variances are unequal across groups. The sampling scheme proposed
      is based on a solution to bandit problems called Thompson sampling. While this
      approach is most often used to maximize the cumulative payoff over competing
      treatments, we show that the same method can also be used to balance exploration
      and exploitation when the aim of the experimenter is to efficiently increase
      estimation precision. We introduce this novel design optimization method and, by
      simulation, show its effectiveness. 

PMID- 25052360
TI  - Italian guidelines on thrombolysis indications in ischemic stroke have been
      revised after the IST-3 trial and Cochrane review.

PMID- 25052361
TI  - Characteristics, management modalities and outcome in chronic systolic heart
      failure patients treated in tertiary care centers: results from the EVIdence
      based TreAtment in Heart Failure (EVITA-HF) registry.
AB  - BACKGROUND: Limited data exist regarding baseline characteristics and management
      of heart failure with reduced ejection fraction (EF) in tertiary care facilities.
      METHODS: EVITA-HF comprises web-based case report data on demography,
      comorbidities, diagnostic and therapy measures, quality of life, adverse events
      and 1-year follow-up of patients hospitalized for chronic heart failure and an
      ejection fraction of less than 40%. RESULTS: Between February 2009 and June 2011,
      a total of 1,853 consecutive, hospitalized patients (pts) were included in 16
      centers in Germany. Mean age was 70 years, 76% were male. Median EF was 30%, and
      63% were in NYHA III/IV. Ischemic cardiomyopathy was present in 56%, history of
      hypertension in 76%, diabetes in 39%, impaired renal function in 33%, thyroid
      dysfunction in 12%, and malignoma in 7%. Sixty-eight percent of pts had a non
      elective admission. Rhythm was sinus/atrial fibrillation or flutter/pacemaker in
      64, 28 and 11%, respectively. Median heart rate amounted to 80 bpm, median blood
      pressure to 122/74 mmHg. LBBB was present in 26% of non-pacemaker pts. Eighteen
      percent had an ICD or CRT-D. Medication (admission vs. discharge) consisted of
      ACEI or ARB in 73 vs. 88%, beta-blocker in 71 vs. 89%, mineral corticosteroid
      receptor antagonist (MRA) in 32 vs. 57%, diuretics in 68 vs. 83% (p < 0.001 for
      each). Forty-two percent of pts received a specific treatment procedure beyond
      pharmacotherapy, of these 48% revascularization, 39% device therapy, 14%
      electrical cardioversion, 5% ablation procedures, 9 % valvular procedures, 6% iv
      inotropes, 1.8% IABP or LVAD implantation. At discharge, 33% of survivors had ICD
      or CRT-D implants. One-year mortality amounted to 16.8%, and death or
      rehospitalization to 56%. NYHA class III/IV was found in 30% (p < 0.001 vs. index
      admission), general health status was improved in 45% and unchanged in 36% of
      patients. Eighty-five percent of pts took ACEI or ARB, 86% beta-blockers, 47%
      MRA, and 78% diuretics (p < 0.001 vs. index discharge for all). CONCLUSION:
      Patients with chronic heart failure and low ejection fraction represent an
      elderly and multimorbid population. While hospitalized, they experience a
      significant optimization of prognosis-relevant medication, revascularization and
      device therapy. After 1 year, mortality is moderate; drug adherence is high and
      NYHA status favourable. The EVITA-HF registry is able to reflect coherently the
      real-world management, efforts and follow-up in heart failure pts managed in
      tertiary care facilities.

PMID- 25052362
TI  - Melatonin receptor-mediated protection against myocardial ischemia/reperfusion
      injury: role of SIRT1.
AB  - Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion
      (MI/R) injury by reducing oxidative stress. Activation of silent information
      regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that
      melatonin may protect against MI/R injury by activating SIRT1 signaling. This
      study investigated the protective effect of melatonin treatment on MI/R heart and
      elucidated its potential mechanisms. Rats were exposed to melatonin treatment in
      the presence or the absence of the melatonin receptor antagonist luzindole or
      SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a
      cardioprotective effect by improving postischemic cardiac function, decreasing
      infarct size, reducing apoptotic index, diminishing serum creatine kinase and
      lactate dehydrogenase release, upregulating SIRT1, Bcl-2 expression and
      downregulating Bax, caspase-3 and cleaved caspase-3 expression. Melatonin
      treatment also resulted in reduced myocardium superoxide generation, gp91(phox)
      expression, malondialdehyde level, and increased myocardium superoxide dismutase
      (SOD) level, which indicate that the MI/R-induced oxidative stress was
      significantly attenuated. However, these protective effects were blocked by EX527
      or luzindole, indicating that SIRT1 signaling and melatonin receptor may be
      specifically involved in these effects. In summary, our results demonstrate that
      melatonin treatment attenuates MI/R injury by reducing oxidative stress damage
      via activation of SIRT1 signaling in a receptor-dependent manner. 

PMID- 25052363
TI  - Are urinary levels of high mobility group box 1 markers of active nephritis in
      anti-neutrophil cytoplasmic antibody-associated vasculitis?
AB  - The objective of this study is to evaluate urinary high mobility group box 1
      (HMGB1) levels as markers for active nephritis in patients with anti-neutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in comparison with
      urinary CD4(+) effector memory T cells and urinary monocyte chemoattractant
      protein-1 (MCP-1). Twenty-four AAV patients with active nephritis and 12 healthy
      controls (HC) were evaluated. In nine patients, samples were also obtained during
      remission. Urinary levels of HMGB1 were measured by Western blot. CD4(+) T cells
      and CD4(+) effector memory T cells (CD4(+) CD45RO(+) CCR7(-) ) were determined in
      urine and whole blood by flow cytometry. Measurement of urinary levels of MCP-1
      and serum HMGB1 levels were performed by enzyme-linked immunosorbent assay
      (ELISA). AAV patients with active nephritis had higher median intensity of HMGB1
      in urine than HC [10.3 (7.05-18.50) versus 5.8 (4.48-7.01); P = 0.004]. Both
      urinary HMGB1 and MCP-1 levels decreased significantly from active nephritis to
      remission. The urinary MCP-1/creatinine ratio correlated with Birmingham
      Vasculitis Activity Score (BVAS) (P = 0.042). No correlation was found between
      the HMGB1/creatinine ratio and 24-h proteinuria, estimated glomerular filtration
      rate (eGFR), MCP-1/creatinine ratio, BVAS and serum HMGB1. A positive correlation
      was found between urinary HMGB1/creatinine ratio and CD4(+) T cells/creatinine
      ratio (P = 0.028) and effector memory T cells/creatinine ratio (P = 0.039) in
      urine. Urinary HMGB1 levels are increased in AAV patients with active nephritis
      when compared with HC and patients in remission, and urinary HMGB1 levels are
      associated with CD4(+) T cells and CD4(+) effector memory T cells in urine.
      Measurement of urinary HMGB1 may be of additional value in identifying active
      glomerulonephritis in AAV patients.

PMID- 25052364
TI  - Metabolic Phenotyping Guidelines: studying eating behaviour in humans.
AB  - The study of human appetite and eating behaviour has become increasingly
      important in recent years due to the rise in body weight dysregulation through
      both obesity and eating disorders. Adequate control over appetite is paramount
      for the control of body weight and in order to understand appetite, it is
      necessary to measure eating behaviour accurately. So far, research in this field
      has revealed that no single experimental design can answer all research
      questions. Each research question posed will require a specific study design that
      will limit the findings of that study to those particular conditions. For
      example, choices will be made among the use of laboratory or free-living studies,
      time period for examination, specific measurement techniques and investigative
      methodologies employed. It is important that these represent informed decisions
      about what design and which methodology will provide the most meaningful
      outcomes. This review will examine some of the 'gold standard' study designs and
      methodologies currently employed in the study of human appetite and eating
      behaviour. 

PMID- 25052365
TI  - Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis
      combined with hepatic arterial infusion chemotherapy for advanced hepatocellular
      carcinoma.
AB  - AIM: To evaluate the response, survival and safety on 3-D conformal radiotherapy
      (3D-CRT) for major portal vein tumor thrombosis (PVTT) combined with hepatic
      arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma
      (HCC). METHODS: In this retrospective study, 83 advanced HCC patients treated
      with HAIC who met the following criteria were enrolled: (i) PVTT of the main
      trunk or first branch of the portal vein; (ii) no extrahepatic metastasis; (iii)
      Child-Pugh score of 5-7; (iv) performance status of 0 or 1; and (v) no history of
      sorafenib treatment. The response, overall survival (OS), time to treatment
      failure (TTF), post-progression survival (PPS) and safety were compared between
      HAIC combined with 3D-CRT for PVTT (RT group, n = 41) and HAIC alone (non-RT
      group, n = 42). RESULTS: The objective response of PVTT was significantly higher
      in the RT group (56.1%) than in the non-RT group (33.3%), while that of
      intrahepatic tumor and OS were not significantly different between groups. Median
      OS, TTF and PPS were significantly longer in the RT group than in the non-RT
      group (8.6 and 5.0 months, 5.0 and 2.7 months, and 5.3 and 1.5 months,
      respectively) among intrahepatic tumor non-responders to HAIC, whereas those were
      not significantly different between groups among intrahepatic tumor responders to
      HAIC. By multivariate analysis, the combination of 3D-CRT with HAIC was an
      independent contributing factor for OS (hazard ratio, 3.2; 95% confidence
      interval, 1.692-6.021; P < 0.001) among intrahepatic HCC non-responders to HAIC.
      CONCLUSION: 3D-CRT for PVTT combined with HAIC could provide survival benefit to
      non-responder to HAIC.

PMID- 25052367
TI  - Correction of erroneously packed protein's side chains in the NMR structure based
      on ab initio chemical shift calculations.
AB  - In this work, protein side chain (1)H chemical shifts are used as probes to
      detect and correct side-chain packing errors in protein's NMR structures through
      structural refinement. By applying the automated fragmentation quantum
      mechanics/molecular mechanics (AF-QM/MM) method for ab initio calculation of
      chemical shifts, incorrect side chain packing was detected in the NMR structures
      of the Pin1 WW domain. The NMR structure is then refined by using molecular
      dynamics simulation and the polarized protein-specific charge (PPC) model. The
      computationally refined structure of the Pin1 WW domain is in excellent agreement
      with the corresponding X-ray structure. In particular, the use of the PPC model
      yields a more accurate structure than that using the standard (nonpolarizable)
      force field. For comparison, some of the widely used empirical models for
      chemical shift calculations are unable to correctly describe the relationship
      between the particular proton chemical shift and protein structures. The AF-QM/MM
      method can be used as a powerful tool for protein NMR structure validation and
      structural flaw detection. 

PMID- 25052366
TI  - Efficacy and safety of PPC-5650 on experimental rectal pain in patients with
      irritable bowel syndrome.
AB  - PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion
      channel activity, leading to a reduction in the pain signal under up-regulated
      conditions. The non-clinical programme for PPC-5650 supported a role for this
      novel agent in the treatment of pain in patients with irritable bowel syndrome
      (IBS). In patients with IBS, the aims of the study were: (1) to assess the
      efficacy of a single bolus of PPC-5650 locally applied in the rectum using multi
      modal stimulations of the recto sigmoid and (2) to assess the safety profile of
      PPC-5650. The study was a randomized, double-blind, placebo-controlled, cross
      over trial in patients with IBS, excluding females of child-bearing potential.
      The study consisted of a training visit, study visit 1 and 2 and a follow-up
      visit. Rectosigmoid electrical, thermal and mechanical stimulations were
      performed, pain perception was rated on a pain intensity scale and referred pain
      areas were assessed. All adverse events were registered. Twenty-five patients
      with IBS were enrolled and completed the study (9 women and 16 men; mean age 50.4
      +/- 12.7 years). No effects of the study drug were found on any of the rectal
      stimulations or for referred pain areas (all p > 0.05). No significant or
      clinically relevant treatment-related differences were seen for the laboratory
      safety variables or any other reported adverse event. In conclusion, in patients
      with IBS on rectal sensitivity to multi-modal stimulations, PPC-5650 did not
      produce efficacy relative to placebo. The overall safety and tolerability of PPC
      5650 was acceptable. 

PMID- 25052368
TI  - Cognitive benefits of last night's sleep: daily variations in children's sleep
      behavior are related to working memory fluctuations.
AB  - BACKGROUND: Recent studies have suggested substantial fluctuations of cognitive
      performance in adults both across and within days, but very little is known about
      such fluctuations in children. Children's sleep behavior might have an important
      influence on their daily cognitive resources, but so far this has not been
      investigated in terms of naturally occurring within-person variations in
      children's everyday lives. METHODS: In an ambulatory assessment study, 110
      elementary school children (8-11 years old) completed sleep items and working
      memory tasks on smartphones several times per day in school and at home for 4
      weeks. Parents provided general information about the children and their sleep
      habits. RESULTS: We identified substantial fluctuations in the children's daily
      cognitive performance, self-reported nightly sleep quality, time in bed, and
      daytime tiredness. All three facets were predictive of performance fluctuations
      in children's school and daily life. Sleep quality and time in bed were
      predictive of performance in the morning, and afternoon performance was related
      to current tiredness. The children with a lower average performance level showed
      a higher within-person coupling between morning performance and sleep quality.
      CONCLUSIONS: Our findings contribute important insights regarding a potential
      source of performance fluctuations in children. The effect of varying cognitive
      resources should be investigated further because it might impact children's daily
      social, emotional, and learning-related functioning. Theories about children's
      cognitive and educational development should consider fluctuations on micro
      longitudinal scales (e.g., day-to-day) to identify possible mechanisms behind
      long-term changes.

PMID- 25052369
TI  - Understanding the specificity of serpin-protease complexes through interface
      analysis.
AB  - Serpins such as antithrombin, heparin cofactor II, plasminogen activator
      inhibitor, antitrypsin, antichymotrypsin, and neuroserpin are involved in
      important biological processes by inhibiting specific serine proteases.
      Initially, the protease recognizes the mobile reactive loop of the serpin
      eliciting conformational changes, where the cleaved loop together with the
      protease inserts into beta-sheet A, translocating the protease to the opposite
      side of inhibitor leading to its inactivation. Serpin interaction with proteases
      is governed mainly by the reactive center loop residues (RCL). However, in some
      inhibitory serpins, exosite residues apart from RCL have been shown to confer
      protease specificity. Further, this forms the basis of multi-specificity of some
      serpins, but the residues and their dimension at interface in serpin-protease
      complexes remain elusive. Here, we present a comprehensive structural analysis of
      the serpin-protease interfaces using bio COmplexes COntact MAPS (COCOMAPS),
      PRotein Interface Conservation and Energetics (PRICE), and ProFace programs. We
      have carried out interface, burial, and evolutionary analysis of different serpin
      protease complexes. Among the studied complexes, non-inhibitory serpins exhibit
      larger interface region with greater number of residue involvement as compared to
      the inhibitory serpins. On comparing the multi-specific serpins (antithrombin and
      antitrypsin), a difference in the interface area and residue number was observed,
      suggestive of a differential mechanism of action of these serpins in regulating
      their different target proteases. Further, detailed study of these multi-specific
      serpins listed few essential residues (common in all the complexes) and certain
      specificity (unique to each complex) determining residues at their interfaces.
      Structural mapping of interface residues suggested that individual patches with
      evolutionary conserved residues in specific serpins determine their specificity
      towards a particular protease. 

PMID- 25052370
TI  - Are pricing and reimbursement decision-making criteria aligned with public
      preferences regarding allocation principles in the Polish healthcare sector?
AB  - Given growing interest in multicriteria decision making and multiple cost
      effectiveness thresholds' approach, it was decided to investigate its usefulness
      in Poland. The pricing and reimbursement (P&R) regulations were reviewed and a
      cross-sectional survey was conducted amongst nurses. The study investigated
      whether P&R rules are aligned with the preferences of healthcare professional
      towards the concept of equity. The references to aversion to inequalities in
      health and capacity to benefit were recognized as the most and least important
      principle respectively by the group of nurses. Different weightings of health
      gain dependent on disease severity were accepted by half of the study's
      population. In the review of legal acts, references to capacity to benefit were
      frequently found. The opposite was registered for other concepts of equity. There
      is room for further improvement with respect to the alignment between the Polish
      P&R decision making criteria and public preferences regarding allocation
      principles. 

PMID- 25052371
TI  - Open bite as a risk factor for orthodontic root resorption.

PMID- 25052372
TI  - Reply: To PMID 23307804.

PMID- 25052373
TI  - Short-term treatment effects produced by the Twin-block appliance: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To evaluate dental, skeletal, and soft tissue effects during Twin
      block treatment. METHODS: A systematic search of several electronic databases
      (Medline, PubMed, Embase, all EBM reviews, and Web of Science) was conducted
      until July 2013, as well as a limited grey-literature search (Google Scholar).
      Human cephalometric studies that used a Twin-block appliance in a non-extraction
      and non-surgical approach were selected. A comparable control group of untreated
      subjects was required. Two authors independently reviewed and extracted data from
      the selected studies. Risk of bias was assessed. The type of meta-analysis was
      selected based on heterogeneity. RESULTS: Ultimately 10 articles were included.
      Proclination of lower incisors, retroclination of upper incisors, distal movement
      of upper molars and/or mesial movement of lower molars, increase in mandibular
      length, and/or forward movement of the mandible were consistently reported.
      Clinically significant restraint of maxillary growth was not found. Although the
      mandibular body length is increased, the facial impact of it is reduced by the
      simultaneous increment of the face height. Changes of lower face height and
      occlusal plane inclination varied, suggesting that vertical dimension can be
      manipulated in patients who would benefit from lower molar extrusion. As for lip
      position, there is not enough evidence to suggest clear lip position changes.
      CONCLUSIONS: Changes associated with a Class II correction were identified. Most
      of the changes individually were of limited clinical significance, but when
      combined reached clinical importance. No long-term changes were available.

PMID- 25052374
TI  - Time relevance, citation of reporting guidelines, and breadth of literature
      search in systematic reviews in orthodontics.
AB  - INTRODUCTION: As the importance of systematic review (SR) conclusions relies upon
      the scientific rigor of methods and the currency of evidence, we aimed to
      investigate the currency of orthodontic SRs using as proxy the time from the
      initial search to publication. Additionally, SR information regarding reporting
      guidelines, registration, and literature searches were recorded when available.
      MATERIALS AND METHODS: A systematic PubMed search was carried out using the
      Clinical Queries page to identify orthodontic SRs cited between 1 January 2008
      and 7 November 2013. Data related to reporting guidelines, review registration,
      dates of review processing, literature search, and abstract reporting were
      retrieved and classified by journal type. Survival analysis was used to assess
      the time to reach predefined manuscript stages for orthodontic and non
      orthodontic journals. RESULTS: One hundred twenty seven of the originally
      identified 585 SRs were considered eligible. The median interval from search
      until publication was 13.2 months (interquartile range: IQR = 9.7 months)
      irrespective of the journal type. There was evidence (P = 0.05) that SRs
      published by non-orthodontic journals appeared in PubMed faster than in
      orthodontic journals (non-orthodontic: median = 6.5 months; IQR = 5.7 months;
      orthodontic: median = 10.2 months; IQR = 5.6 months) from submission to
      publication and from acceptance to publication (non-orthodontic: median = 1.5
      months; IQR = 2.4 months; orthodontic: median = 6.0 months; IQR = 6.2 months; P <
      0.001). More than half of these SRs did not cite adherence to any reporting
      guidelines, whereas all but five studies were not prospectively registered.
      Search of unpublished research was undertaken in approximately 21 per cent and 29
      per cent of the SRs published in non-orthodontic and orthodontic periodicals,
      respectively. CONCLUSIONS: This study indicates that SR users should be aware
      that median time for orthodontic SRs from search to publication is 13.2 months.
      SRs published in non-orthodontic journals are likely to be more current in terms
      of submission until time to publication and acceptance until time to publication
      compared with those published in orthodontic journals.

PMID- 25052375
TI  - Metal-free protodeboronation of electron-rich arene boronic acids and its
      application to ortho-functionalization of electron-rich arenes using a boronic
      acid as a blocking group.
AB  - The metal-free thermal protodeboronation of various electron-rich arene boronic
      acids was studied. Several reaction parameters controlling this
      protodeboronation, such as solvent, temperature, and a proton source, have been
      investigated. On the basis of these studies, suitable reaction conditions for
      protodeboronation of several types of electron-rich arene boronic acids were
      provided. On the basis of this protodeboronation, a new protocol for the
      synthesis of ortho-functionalized electron-rich arenes from these boronic acids
      was developed using the boronic acid moiety as a blocking group in the
      electrophilic aromatic substitution reaction, followed by the removal of the
      boronic acid moiety via thermal protodeboronation. Mechanistic studies suggested
      that this protodeboronation might proceed via the complex formation of a boronic
      acid with a proton source, followed by the carbon-boron bond fission through
      sigma-bond metathesis, to afford the corresponding arene compound and boric acid.

PMID- 25052378
TI  - Open book assessment in medical school.

PMID- 25052379
TI  - Macrophage density and macrophage colony-stimulating factor expression predict
      the postoperative prognosis in patients with intrahepatic cholangiocarcinoma.
AB  - PURPOSES: Macrophages are included in the stromal compartments in various
      neoplasms, and their behavior against tumors is diverse. The aim of this study
      was to examine the role of tumor-infiltrating macrophages and their main
      regulator, macrophage colony-stimulating factor (M-CSF), in intrahepatic
      cholangiocarcinoma (ICC). METHODS: Macrophage density and M-CSF expression in 39
      resected ICC specimens were immunohistochemically evaluated in the central and
      peripheral areas of tumors, which were defined as fields more than and within 500
      MUm from the invasive front, respectively. The number of CD68-positive
      macrophages was counted using an image-analyzing software program. The
      relationship between these results and other clinicopathological factors and the
      postoperative prognosis were evaluated. RESULTS: Sporadic M-CSF expression in
      cancer cells around the peripheral area was observed in fourteen patients. M-CSF
      positive ICCs showed a higher macrophage density in the tumor-peripheral area
      than did M-CSF-negative ICCs. M-CSF expression and higher macrophage density in
      the tumor-peripheral area were related to a better postoperative prognosis,
      whereas a higher macrophage density in the central area was one of the
      significant risk factors for a poor prognosis in a univariate analysis.
      CONCLUSION: Tumor-peripheral macrophage infiltration, presumably dependent on M
      CSF, and M-CSF-independent tumor-central macrophage infiltration are predictive
      factors for better and worse postoperative prognosis in ICC patients,
      respectively. The tumor microenvironment, such as the presence of hypoxia, may
      affect the behavior of infiltrating macrophages in ICC.

PMID- 25052380
TI  - Effects of time-invariant covariates on the estimation of longitudinal trends for
      transition mixed models.
AB  - In this paper, we investigate the impact of time-invariant covariates when
      fitting transition mixed models. This is carried out by emphasizing on the role
      of baseline responses on the estimation process. Transition models are allowed
      for two cases of exogenous and endogenous baseline responses. We illustrate these
      concepts in the special case of transition linear mixed models with centered time
      varying covariates. Results of our simulation studies show that the omission, or
      the inclusion, of time-invariant covariates is not important in models with
      exogenous baseline responses, while it has an essential effect on fitting models
      with the endogenous baseline responses. It is also emphasized that the effect
      becomes minor when the endogeneity issue is handled. The practical consequences
      are illustrated in the analysis of a real data set taken from medical sciences.

PMID- 25052376
TI  - Ionic mechanisms in pancreatic beta cell signaling.
AB  - The function and survival of pancreatic beta cells critically rely on complex
      electrical signaling systems composed of a series of ionic events, namely fluxes
      of K(+), Na(+), Ca(2+) and Cl(-) across the beta cell membranes. These electrical
      signaling systems not only sense events occurring in the extracellular space and
      intracellular milieu of pancreatic islet cells, but also control different beta
      cell activities, most notably glucose-stimulated insulin secretion. Three major
      ion fluxes including K(+) efflux through ATP-sensitive K(+) (KATP) channels, the
      voltage-gated Ca(2+) (CaV) channel-mediated Ca(2+) influx and K(+) efflux through
      voltage-gated K(+) (KV) channels operate in the beta cell. These ion fluxes set
      the resting membrane potential and the shape, rate and pattern of firing of
      action potentials under different metabolic conditions. The KATP channel-mediated
      K(+) efflux determines the resting membrane potential and keeps the excitability
      of the beta cell at low levels. Ca(2+) influx through CaV1 channels, a major type
      of beta cell CaV channels, causes the upstroke or depolarization phase of the
      action potential and regulates a wide range of beta cell functions including the
      most elementary beta cell function, insulin secretion. K(+) efflux mediated by
      KV2.1 delayed rectifier K(+) channels, a predominant form of beta cell KV
      channels, brings about the downstroke or repolarization phase of the action
      potential, which acts as a brake for insulin secretion owing to shutting down the
      CaV channel-mediated Ca(2+) entry. These three ion channel-mediated ion fluxes
      are the most important ionic events in beta cell signaling. This review concisely
      discusses various ionic mechanisms in beta cell signaling and highlights KATP
      channel-, CaV1 channel- and KV2.1 channel-mediated ion fluxes. 

PMID- 25052377
TI  - Senescence suppressors: their practical importance in replicative lifespan
      extension in stem cells.
AB  - Recent animal and clinical studies report promising results for the therapeutic
      utilization of stem cells in regenerative medicine. Mesenchymal stem cells
      (MSCs), with their pluripotent nature, have advantages over embryonic stem cells
      in terms of their availability and feasibility. However, their proliferative
      activity is destined to slow by replicative senescence, and the limited
      proliferative potential of MSCs not only hinders the preparation of sufficient
      cells for in vivo application, but also draws a limitation on their potential for
      differentiation. This calls for the development of safe and efficient means to
      increase the proliferative as well as differentiation potential of MSCs. Recent
      advances have led to a better understanding of the underlying mechanisms and
      significance of cellular senescence, facilitating ways to manipulate the
      replicative lifespan of a variety of primary cells, including MSCs. This paper
      introduces a class of proteins that function as senescence suppressors. Like
      tumor suppressors, these proteins are lost in senescence, while their forced
      expression delays the onset of senescence. Moreover, treatments that increase the
      expression or the activity of senescence suppressors, therefore, cause expansion
      of the replicative and differentiation potential of MSCs. The nature of the
      activities and putative underlying mechanisms of the senescence suppressors will
      be discussed to facilitate their evaluation. 

PMID- 25052381
TI  - Immunophenotypic characterization of canine malignant lymphoma: a retrospective
      study of cases diagnosed in Poland Lower Silesia, over the period 2011-2013.
AB  - Lymphoma is the most frequently diagnosed cancer of the canine haematopoietic
      system. In this study, the flow cytometry and polymerase chain reaction (PCR)
      analysis were used to characterize a series of canine lymphomas in detail. The
      aim of this study was to determine the incidence of B- and T-cell high-grade
      lymphomas and their immunophenotypic characterization in Lower Silesia, Poland.
      The results show that the frequency of each type of lymphoma is 71% for B-cell
      and 17% for T-cell lymphomas. In two cases the PCR techniques confirmed the
      presence of simultaneous double gene rearrangements of the BCR and TCR receptors.

PMID- 25052382
TI  - On the homology of the shoulder girdle in turtles.
AB  - The shoulder girdle in turtles is encapsulated in the shell and has a triradiate
      morphology. Due to its unique configuration among amniotes, many theories have
      been proposed about the skeletal identities of the projections for the past two
      centuries. Although the dorsal ramus represents the scapular blade, the ventral
      two rami remain uncertain. In particular, the ventrorostral process has been
      compared to a clavicle, an acromion, and a procoracoid based on its morphology,
      its connectivity to the rest of the skeleton and to muscles, as well as with its
      ossification center, cell lineage, and gene expression. In making these
      comparisons, the shoulder girdle skeleton of anurans has often been used as a
      reference. This review traces the history of the debate on the homology of the
      shoulder girdle in turtles. And based on the integrative aspects of developmental
      biology, comparative morphology, and paleontology, we suggest acromion and
      procoracoid identities for the two ventral processes.

PMID- 25052383
TI  - Isolation, characterization and community diversity of indigenous putative
      toluene-degrading bacterial populations with catechol-2,3-dioxygenase genes in
      contaminated soils.
AB  - Indigenous bacterial assemblages with putative hydrocarbon-degrading capabilities
      were isolated, characterized and screened for the presence of the catechol-2,3
      dioxygenase (C23O) gene after exposure to toluene in two different (i.e.,
      pristine and conditioned) soil communities. The indigenous bacterial populations
      were exposed to the hydrocarbon substrate by the addition of toluene
      concentrations, ranging from 0.5 % to 10 % V/W in 10 g of each soil and incubated
      at 30  degrees C for upwards of 12 days. In total, 25 isolates (11 in pristine
      soil and 14 in conditioned soil) were phenotypically characterized according to
      standard microbiological methods and also screened for the 238-bp C23O gene
      fragment. Additionally, 16S rRNA analysis of the isolates identified some of them
      as belonging to the genera Bacillus, Exiguobacterium, Enterobacter, Pseudomonas
      and Stenotrophomonas. Furthermore, the two clone libraries that were constructed
      from these toluene-contaminated soils also revealed somewhat disparate phylotypes
      (i.e., 70 % Actinobacteria and Firmicutes to 30 % Proteobacteria in conditioned
      soil, whereas in pristine soil: 66 % Actinobacteria and Firmicutes; 21 %
      Proteobacteria and 13 % Bacteroidetes). The differences observed in bacterial
      phylotypes between these two soil communities may probably be associated with
      previous exposure to hydrocarbon sources by indigenous populations in the
      conditioned soil as compared to the pristine soil.

PMID- 25052384
TI  - Magnetic resonance imaging of melanoma exosomes in lymph nodes.
AB  - PURPOSE: Exosomes are cell derived extracellular nanovesicles that relay
      molecular signals pertinent to both normal physiologic and disease processes. The
      ability to modify and track exosomes in vivo is essential to understanding
      exosome pathogenesis, and for utilizing exosomes as effective diagnostic and
      therapeutic nanocarriers to treat diseases. METHODS: We recently reported a new
      electroporation method that allow exosomes to be loaded with superparamagnetic
      iron oxide nanoparticles for magnetic resonance tracking. RESULTS: Building on
      this approach, we now demonstrate for the first time using a C57BL/6 mouse model
      that melanoma exosomes can be imaged in vitro, and within lymph nodes in vivo
      with the use of standard MRI approaches. CONCLUSION: These findings demonstrate
      proof of principle that exosome biology can be followed in vivo and pave the way
      for the development of future diagnostic and therapeutic applications. Magn Reson
      Med 74:266-271, 2015. (c) 2014 Wiley Periodicals, Inc.

PMID- 25052385
TI  - Declining efficacy of artesunate plus sulphadoxine-pyrimethamine in northeastern
      India.
AB  - BACKGROUND: Anti-malarial drug resistance in Plasmodium falciparum in India has
      historically travelled from northeast India along the Myanmar border. The
      treatment policy for P. falciparum in the region was, therefore, changed from
      chloroquine to artesunate (AS) plus sulphadoxine-pyrimethamine (SP) in selected
      areas in 2005 and in 2008 it became the first-line treatment. Recognizing that
      resistance to the partner drug can limit the useful life of this combination
      therapy, routine in vivo and molecular monitoring of anti-malarial drug efficacy
      through sentinel sites was initiated in 2009. METHODS: Between May and October
      2012, 190 subjects with acute uncomplicated falciparum malaria were enrolled in
      therapeutic efficacy studies in the states of Arunachal Pradesh, Tripura, and
      Mizoram. Clinical and parasitological assessments were conducted over 42 days of
      follow-up. Multivariate analysis was used to determine risk factors associated
      with treatment failure. Genotyping was done to distinguish re-infection from
      recrudescence as well as to determine the prevalence of molecular markers of
      antifolate resistance among isolates. RESULTS: A total of 169 patients completed
      42 days of follow-up at three sites. The crude and PCR-corrected Kaplan-Meier
      survival estimates of AS + SP were 60.8% (95% CI: 48.0-71.4) and 76.6% (95% CI:
      64.1-85.2) in Gomati, Tripura; 74.6% (95% CI: 62.0-83.6) and 81.7% (95% CI: 69.4
      89.5) in Lunglei, Mizoram; and, 59.5% (95% CI: 42.0-73.2) and 82.3% (95% CI: 64.6
      91.6) in Changlang, Arunachal Pradesh. Most patients with P. falciparum cleared
      parasitaemia within 24 hours of treatment, but eight, including three patients
      who failed treatment, remained parasitaemic on day 3. Risk factors associated
      with treatment failure included age < five years, fever at the time of enrolment
      and AS under dosing. No adverse events were reported. Presence of dhfr plus dhps
      quintuple mutation was observed predominantly in treatment failure samples.
      CONCLUSION: AS + SP treatment failure was widespread in northeast India and
      exceeded the threshold for changing drug policy. Based on these results, in
      January 2013 the expert committee of the National Vector Borne Disease Control
      Programme formulated the first subnational drug policy for India and selected
      artemether plus lumefantrine as the new first-line treatment in the northeast.
      Continued monitoring of anti-malarial drug efficacy is essential for effective
      malaria control.

PMID- 25052386
TI  - Roles of resolvins in the resolution of acute inflammation.
AB  - Resolution is an active process that terminates inflammatory response to maintain
      health. Acute inflammation and its timely resolution are important in host
      response to danger signals. Unresolved inflammation is associated with widely
      recurrent diseases. Resolvins, including the D and E series, are endogenous lipid
      mediators generated during the resolution phase of acute of inflammation from the
      omega-3 PUFAs, DHA, and EPA. They have anti-inflammatory and pro-resolving
      properties that have been determined in many inflammation studies in animal
      models. In this review, we provide an updated overview of biosynthesis, actions,
      and signaling pathways of resolvins, thereby underscoring their diverse
      protective roles and introducing novel therapeutic strategies for inflammation
      associated diseases. 

PMID- 25052387
TI  - Cost-utility analysis of a telehealth programme for patients with severe chronic
      obstructive pulmonary disease treated with long-term oxygen therapy.
AB  - We conducted a cost-utility analysis of a telehealth programme for patients with
      severe chronic obstructive pulmonary disease (COPD) compared with usual care. A
      randomized controlled trial was carried out over four months with 45 patients
      treated with long-term oxygen therapy, 24 in the telehealth group (TG) and 21 in
      the control group (CG). The analysis took into account whether the severity of
      comorbidity (defined as the presence of additional chronic diseases co-occurring
      with COPD) was associated with differences in costs and/or quality-adjusted life
      years (QALYs). Results of cost-utility analysis were expressed in terms of the
      incremental cost-effectiveness ratio (ICER). The average total cost was ?2300 for
      the TG and ?1103 for the CG, and the average QALY gain was 0.0059 for the TG and
      0.0006 for the CG (resulting an ICER of 223,726 ?/QALY). For patients without
      comorbidity, the average total cost was ?855 for the TG and ?1354 for the CG, and
      the average QALY gain was 0.0288 for the TG and 0.0082 for the CG (resulting in
      the telehealth programme being the dominant strategy). For patients with
      comorbidity, the average total cost was ?2782 for the TG and ?949 for the CG, and
      the average QALY gain was -0.0017 for the TG and -0.0041 for the CG (resulting an
      ICER of 754,592 ?/QALY). The telehealth programme may not have been cost
      effective compared to usual care, although it could be considered cost-effective
      for patients without comorbidity.

PMID- 25052388
TI  - Use of a mental health emergency care-rural access programme in emergency
      departments.
AB  - Hospital emergency departments (EDs) are common providers of emergency mental
      health care. Access to specialist expertise can affect and improve patient
      outcomes. The Mental Health Emergency Care-Rural Access Programme (MHEC) provides
      access to mental health specialists for rural and remote communities in western
      New South Wales. In 2011, 46 of the 48 EDs used the MHEC programme, which
      provided 1487 clinical services, an average of 29 services per week. This
      represented 60% of all MHEC activity. A video assessment was conducted during 571
      (38%) of these MHEC contacts. Patients attending a non-base hospital (<50 beds)
      were twice as likely to receive a video assessment as those attending the larger
      base hospitals, and video was used more with increasing remoteness. Patients from
      non-base hospitals were also more likely to be admitted locally after a video
      assessment. When a decision to admit was made, patients from non-base hospital
      EDs assessed by video were less likely to be transferred out of their community
      to a mental health inpatient unit than those assessed by telephone triage only
      (46% vs 62%; P = 0.016). The MHEC programme is a practical, relevant and
      responsive solution that was designed for the Australian health system, but the
      same model could be adapted for implementation in other countries.

PMID- 25052389
TI  - Telehealth for improved glycaemic control in patients with poorly controlled
      diabetes after acute hospitalization - a preliminary study in Singapore.
AB  - We evaluated a disease management and education programme delivered via telephone
      support (TS) to patients with poorly controlled diabetes (HbA1c >7%). All
      eligible patients were invited to participate in the programme, which involved
      education on lifestyle modification and disease management delivered via three
      scheduled monthly calls by trained nurses. Patients who declined or could not be
      contacted acted as the controls (usual care, UC). A per protocol analysis was
      conducted using a mixed effect model for two subgroups with different baseline
      HbA1c levels (i.e. baseline HbA1c <8.0% and HbA1c >=8.0%). A total of 2646
      patients with diabetes were eligible for enrolment. Of these, 1391 participants
      had HbA1c measurements available. The study comprised 633 patients (46%) who
      completed the programme (TS), 598 (43%) who were not contactable or refused to
      participate at the first telephone call (UC) and 160 patients who dropped out. In
      the patients with HbA1c >=8%, TS reduced the adjusted mean HbA1c by 0.38% (P =
      0.022) but the reduction in diabetes-related admissions (4.2% lower adjusted mean
      admission rate) was not significant. In patients with HbA1c <8%, TS had no
      additional effect on glycaemic control or diabetes-related admission. Telephone
      support appeared effective in improving glycaemic control in patients with poor
      diabetes control.

PMID- 25052390
TI  - Rapid Syllable Transitions (ReST) treatment for Childhood Apraxia of Speech: the
      effect of lower dose-frequency.
AB  - This study investigated the effectiveness of twice-weekly Rapid Syllable
      Transitions (ReST) treatment for Childhood Apraxia of Speech (CAS). ReST is an
      effective treatment at a frequency of four sessions a week for three consecutive
      weeks. In this study we used a multiple-baselines across participants design to
      examine treatment efficacy for four children with CAS, aged four to eight years,
      who received ReST treatment twice a week for six weeks. The children's ability to
      acquire new skills, generalize these skills to untreated items and maintain the
      skills after treatment was examined. All four children improved their production
      of the target items. Two of the four children generalized the treatment effects
      to similar untreated pseudo words and all children generalized to untreated real
      words. During the maintenance phase, all four participants maintained their
      skills to four months post-treatment, with a stable rather than rising profile.
      This study shows that ReST treatment delivered twice-weekly results in
      significant retention of treatment effects to four months post-treatment and
      generalization to untrained but related speech behaviors. Compared to ReST
      therapy four times per week, the twice-weekly frequency produces similar
      treatment gains but no ongoing improvement after the cessation of treatment. This
      implies that there may be a small but significant benefit of four times weekly
      therapy compared with twice-weekly ReST therapy. LEARNING OUTCOMES: Readers will
      be able to define dose-frequency, and describe how this relates to overall
      intervention intensity. Readers will be able to explain the acquisition,
      generalization and maintenance effects in the study and describe how these
      compare to higher dose frequency treatments. Readers will recognize that the
      current findings give preliminary support for high dose-frequency CAS treatment.

PMID- 25052391
TI  - Tessaracoccus lapidicaptus sp. nov., an actinobacterium isolated from the deep
      subsurface of the Iberian pyrite belt.
AB  - A novel actinobacterium, designated IPBSL-7(T), was isolated from a drilling core
      297 m deep obtained from the Iberian Pyrite Belt. The strain was isolated
      anaerobically using nitrate as the electron acceptor. 16S rRNA gene sequence
      analysis revealed that it was related to Tessaracoccus flavescens SST-39(T)
      (95.7% similarity), Tessaracoccus bendigoensis Ben 106(T) (95.7%), Tessaracoccus
      lubricantis KSS-17Se(T) (95.6%) and Tessaracoccus oleiagri SL014B-20A1(T)
      (95.0%), while its similarity to any other member of the family
      Propionibacteriaceae was less than 94%. Cells were non-motile, non-spore-forming,
      Gram-positive, oval to rod-shaped, and often appeared in pairs or small groups.
      The strain was facultatively anaerobic, oxidase-negative, catalase-positive and
      capable of reducing nitrate. Colonies were circular, convex, smooth and
      colourless. The organism could grow at between 15 and 40  degrees C, with an
      optimal growth at 37  degrees C. The pH range for growth was from pH 6 to 9, with
      pH 8 being the optimal value. Strain IPBSL-7(T) had peptidoglycan type A3-gamma',
      with ll-diaminopimelic acid as the diagnostic diamino-acid and glycine at
      position 1 of the peptide subunit. The dominant menaquinone was MK-9(H4) (93.8%).
      The major cellular fatty acid was anteiso-C15:0 (55.0%). The DNA G+C content was
      70.3 mol%. On the basis of phenotypic and phylogenetic results, strain IPBSL-7(T)
      can be differentiated from previously described species of the genus
      Tessaracoccus and, therefore, represents a novel species, for which the name
      Tessaracoccus lapidicaptus sp. nov. is proposed. The type strain is IPBSL-7(T) (
      = CECT 8385(T) = DSM 27266(T)).

PMID- 25052392
TI  - Allokutzneria oryzae sp. nov., isolated from rhizospheric soil of Oryza sativa L.
AB  - The taxonomic status of a rhizospheric soil actinomycete, designated R8-39(T),
      was established using a polyphasic approach. The organism had phenotypic and
      morphological characteristics consistent with its classification in the genus
      Allokutzneria. Phylogenetic analysis based on an almost complete 16S rRNA gene
      sequence showed that the strain formed a monophyletic clade with the type strains
      of members of the genus Allokutzneria. Strain R8-39(T) displayed the highest
      levels of 16S rRNA gene sequence similarity to Allokutzneria albata DSM 44149(T)
      (98.8%) and Allokutzneria multivorans YIM 120521(T) (98.3%). However, the DNA-DNA
      hybridization values between strain R8-39(T) and A. albata and A. multivorans
      were clearly below the 70% threshold. The organism was found to have chemical
      characteristics consistent with its classification in the genus Allokutzneria.
      Whole-cell hydrolysates contained meso-diaminopimelic acid, arabinose, galactose,
      glucose, mannose, rhamnose and ribose. The main menaquinone was MK-9(H4). No
      mycolic acid was detected. The G+C content of the genomic DNA was 71.8 mol%. In
      addition, strain R8-39(T) had a phenotypic profile that readily distinguished it
      from recognized representatives of the genus Allokutzneria. It is evident from
      the combined genotypic and phenotypic properties that strain R8-39(T) represents
      a novel species of the genus Allokutzneria. The proposed name for this species is
      Allokutzneria oryzae sp. nov.; the type strain is R8-39(T) ( = BCC 60399(T) =
      NBRC 109649(T)).

PMID- 25052393
TI  - Phaeodactylibacter xiamenensis gen. nov., sp. nov., a member of the family
      Saprospiraceae isolated from the marine alga Phaeodactylum tricornutum.
AB  - A novel Gram-staining-negative, aerobic, rod-shaped, non-motile, reddish-orange
      and chemoheterotrophic bacteria, designated strain KD52(T), was isolated from a
      culture of the alga Phaeodactylum tricornutum from Xiamen, Fujian Province,
      China. 16S rRNA gene sequence comparison showed that strain KD52(T) was a member
      of the family Saprospiraceae, forming a distinct lineage with 'Portibacter lacus'
      KCTC 23747. The 16S rRNA gene sequence similarity between strain KD52(T) and the
      type strains of species of the family Saprospiraceae ranged from 86% to 89%.
      Growth occurred at 20-37  degrees C (optimum, 28  degrees C), in the presence of
      1-9% (w/v) NaCl (optimum, 2.5%) and at pH 5-8.5 (optimum, pH 6.0). The dominant
      fatty acids (>10%) of strain KD52(T) were iso-C15:0 (33.1%), iso-C15:1 G (14.8%)
      and summed feature 3 (comprising C16:1omega7c and/or C16:1omega6c, 13.8%). The
      major polar lipids were diphosphatidylglycerol, three unidentified phospholipids,
      four unknown lipids and one unidentified aminolipid. The DNA G+C content was 51
      mol% and the major respiratory quinone was menaquinone-7 (MK-7). On the basis of
      phenotypic data and phylogenetic inference, strain KD52(T) represents a novel
      species of a new genus, for which the name Phaeodactylibacter xiamenensis gen.
      nov., sp. nov., is proposed. The type strain is KD52(T) ( = MCCC 1F01213(T) =
      KCTC 32575(T)).

PMID- 25052394
TI  - Methanosarcina spelaei sp. nov., a methanogenic archaeon isolated from a floating
      biofilm of a subsurface sulphurous lake.
AB  - A novel methanogenic archaeon, strain MC-15(T), was isolated from a floating
      biofilm on a sulphurous subsurface lake in Movile Cave (Mangalia, Romania). Cells
      were non-motile sarcina-like cocci with a diameter of 2-4 um, occurring in
      aggregates. The strain was able to grow autotrophically on H2/CO2. Additionally,
      acetate, methanol, monomethylamine, dimethylamine and trimethylamine were
      utilized, but not formate or dimethyl sulfide. Trypticase peptone and yeast
      extract were not required for growth. Optimal growth was observed at 33  degrees
      C, pH 6.5 and a salt concentration of 0.05 M NaCl. The predominant membrane
      lipids of MC-15(T) were archaeol and hydroxyarchaeol phosphatidylethanolamine,
      phosphatidylglycerol, and phosphatidylinositol as well as hydroxyarchaeol
      phosphatidylserine and archaeol glycosaminyl phosphatidylinositol. The closely
      related species, Methanosarcina vacuolata and Methanosarcina horonobensis, had a
      similar composition of major membrane lipids to strain MC-15(T). The 16S rRNA
      gene sequence of strain MC-15(T) was similar to those of Methanosarcina vacuolata
      DSM 1232(T) (sequence similarity 99.3%), Methanosarcina horonobensis HB-1(T)
      (98.8%), Methanosarcina barkeri DSM 800(T) (98.7%) and Methanosarcina siciliae
      T4/M(T) (98.4%). DNA-DNA hybridization revealed 43.3% relatedness between strain
      MC-15(T) and Methanosarcina vacuolata DSM 1232(T). The G+C content of the genomic
      DNA was 39.0 mol%. Based on physiological, phenotypic and genotypic differences,
      strain MC-15(T) represents a novel species of the genus Methanosarcina, for which
      the name Methanosarcina spelaei sp. nov. is proposed. The type strain is MC-15(T)
      ( = DSM 26047(T) = JCM 18469(T)).

PMID- 25052395
TI  - Geobacter anodireducens sp. nov., an exoelectrogenic microbe in
      bioelectrochemical systems.
AB  - A previously isolated exoelectrogenic bacterium, strain SD-1(T), was further
      characterized and identified as a representative of a novel species of the genus
      Geobacter. Strain SD-1(T) was Gram-negative, aerotolerant, anaerobic, non-spore
      forming, non-fermentative and non-motile. Cells were short, curved rods (0.8-1.3
      um long and 0.3 um in diameter). Growth of strain SD-1(T) was observed at 15-42 
      degrees C and pH 6.0-8.5, with optimal growth at 30-35  degrees C and pH 7.
      Analysis of 16S rRNA gene sequences indicated that the isolate was a member of
      the genus Geobacter, with the closest known relative being Geobacter
      sulfurreducens PCA(T) (98% similarity). Similar to other members of the genus
      Geobacter, strain SD-1(T) used soluble or insoluble Fe(III) as the sole electron
      acceptor coupled with the oxidation of acetate. However, SD-1(T) could not reduce
      fumarate as an electron acceptor with acetate oxidization, which is an important
      physiological trait for G. sulfurreducens. Moreover, SD-1(T) could grow in media
      containing as much as 3% NaCl, while G. sulfurreducens PCA(T) can tolerate just
      half this concentration, and this difference in salt tolerance was even more
      obvious when cultivated in bioelectrochemical systems. DNA-DNA hybridization
      analysis of strain SD-1(T) and its closest relative, G. sulfurreducens ATCC
      51573(T), showed a relatedness of 61.6%. The DNA G+C content of strain SD-1(T)
      was 58.9 mol%. Thus, on the basis of these characteristics, strain SD-1(T) was
      not assigned to G. sulfurreducens, and was instead classified in the genus
      Geobacter as a representative of a novel species. The name Geobacter
      anodireducens sp. nov. is proposed, with the type strain SD-1(T) ( = CGMCC
      1.12536(T) = KCTC 4672(T)).

PMID- 25052396
TI  - Veillonella seminalis sp. nov., a novel anaerobic Gram-stain-negative coccus from
      human clinical samples, and emended description of the genus Veillonella.
AB  - Ten isolates of unknown, Gram-stain-negative, anaerobic cocci were recovered from
      human clinical samples, mainly from semen. On the basis of their phenotypic
      features, including morphology, main metabolic end products, gas production,
      nitrate reduction and decarboxylation of succinate, the strains were identified
      as members of the genus Veillonella. Multi-locus sequence analysis and
      corresponding phylogenies were based on 16S rRNA, dnaK and rpoB genes, and on the
      newly proposed gltA gene. The strains shared high levels of genetic sequence
      similarity and were related most closely to Veillonella ratti. The strains could
      not be differentiated from V. ratti on the basis of 16S rRNA gene sequence
      analysis while gltA, rpoB and dnaK gene sequences showed 85.1, 93.5 and 90.2%
      similarity with those of the type strain of V. ratti, respectively. Phylogenetic
      analyses revealed that the isolates formed a robust clade in the V. ratti
      Veillonella criceti-Veillonella magna subgroup of the genus Veillonella. As
      observed for V. criceti, the isolates were able to ferment fructose. In contrast
      to other members of the genus Veillonella, the 10 strains were not able to
      metabolize lactate. Cellular fatty acid composition was consistent with that of
      other species of the genus Veillonella. From these data, the 10 isolates are
      considered to belong to a novel species in the genus Veillonella, for which the
      name Veillonella seminalis sp. nov. is proposed. The type strain is ADV 4313.2(T)
      ( = CIP 107810(T) = LMG 28162(T)). Veillonella strain ACS-216-V-Col6b subjected
      to whole genome sequencing as part as the Human Microbiome Project is another
      representative of V. seminalis sp. nov. An emended description of the genus
      Veillonella is also proposed.

PMID- 25052397
TI  - Permianibacter aggregans gen. nov., sp. nov., a bacterium of the family
      Pseudomonadaceae capable of aggregating potential biofuel-producing microalgae.
AB  - A novel bacterial strain, capable of aggregating potential biofuel-producing
      microalgae, was isolated from the phycosphere of an algal culture and designated
      HW001(T). The novel bacterial strain was identified on the basis of its
      phylogenetic, genotypic, chemotaxonomic and phenotypic characteristics in this
      study. Cells were aerobic, Gram-negative rods. 16S rRNA gene-based phylogenetic
      analysis revealed that strain HW001(T) is affiliated with the family
      Pseudomonadaceae in the phylum Proteobacteria, but forms a distinct clade within
      this family. The DNA G+C content of strain HW001(T) was 55.4 mol%. The
      predominant cellular fatty acids were iso-C15:0, summed feature 9 (iso
      C17:1omega9c), C16:0 and summed feature 3 (C16:1omega7c/C16:1omega6c). Q-8 was
      the main respiratory quinone. The polar lipid profile contained
      phosphatidylethanolamine, an unidentified aminophospholipid and some unidentified
      lipids. Based on the extensive polyphasic analysis, strain HW001(T) represents a
      novel species of a new genus in the family Pseudomonadaceae, for which the name
      Permianibacter aggregans gen. nov., sp. nov., is proposed. The type strain of the
      type species is HW001(T) ( = CICC 10856(T) = KCTC 32485(T)).

PMID- 25052398
TI  - Glycomyces artemisiae sp. nov., an endophytic actinomycete isolated from the
      roots of Artemisia argyi.
AB  - An endophytic actinomycete strain, IXS4(T), was isolated from the root of
      Artemisia argyi, a medicinal plant collected from Yesanpo located in Laishui
      county, Hebei province, China. The 16S rRNA gene sequence of strain IXS(T) showed
      most similarity to Glycomyces mayteni YIM 61331(T) (98.23% 16S rRNA gene sequence
      similarity), Glycomyces scopariae YIM 56256(T) (98.00%), Glycomyces sambucus
      E71(T) (97.90%) and Glycomyces algeriensis NRRL B-16327(T) (97.10%). DNA-DNA
      hybridization values between strain IXS4(T) and the closely related type strains
      were well below 70%. The strain also showed a number of physiological and
      biochemical characteristics that were distinct from the closely related species.
      The strain contained MK-10(H2) and MK-11(H0) as the detected menaquinones. The
      peptidoglycan was mainly meso-diaminopimelic acid and the whole-cell sugars
      contained galactose, glucose, mannose, xylose and ribose. The major cellular
      fatty acids were iso-C14:0, iso-C15:0, iso-C16:0, anteiso-C15:0 and anteiso
      C17:0. Based on the genetic and phenotypic properties, it is proposed that strain
      IXS4(T) represents a novel species of the genus Glycomyces, with the name
      http://dx.doi.org/10.1601/nm.7671Glycomyces artemisiae sp. nov. The type strain
      is IXS4(T) ( = HBUM178000(T) = CGMCC 4.7067(T) = NBRC 109773(T)).

PMID- 25052399
TI  - Gordonia iterans sp. nov., isolated from a patient with pneumonia.
AB  - A second novel clinical actinobacterial strain, designated IFM 10348(T), was
      isolated from the sputum of the same Japanese patient with bacterial pneumonia
      from whom the type strain of Gordonia araii had been isolated. The strains
      differed in phylogenetic position and drug-resistance profiles. The taxonomic
      position of strain IFM 10348(T) was clarified by phenotypic, chemotaxonomic and
      phylogenetic studies. Phylogenetic analyses based on 16S rRNA gene sequences
      clearly demonstrated that strain IFM 10348(T) occupied a distinct clade within
      the genus Gordonia and was related closely to Gordonia malaquae DSM 45064(T) and
      Gordonia hirsuta DSM 44140(T) (97.3 and 97.1% similarities, respectively). Strain
      IFM 10348(T) was also clearly differentiated from G. malaquae DSM 45064(T) and G.
      hirsuta DSM 44140(T) based on gyrB and secA1 gene sequence similarity values.
      Strain IFM 10348(T) had MK-9(H2) as the predominant menaquonine, contained meso
      diaminopimelic acid, arabinose, galactose and glucosamine as cell-wall
      components, and contained C18:1omega9c, summed feature 3 (C16:1omega7c and/or
      C16:1omega6c) and C16:0 as the major cellular fatty acids. Mycolic acids were
      present. The DNA G+C content of strain IFM 10348(T) was 68.0 mol%. DNA-DNA
      relatedness data coupled with the combination of genotypic and phenotypic data
      indicated that strain IFM 10348(T) represents a novel species of the genus
      Gordonia, for which the name Gordonia iterans sp. nov. is proposed. The type
      strain is IFM 10348(T) ( = CCTCC M2011245(T) = NCCB 100436(T)).

PMID- 25052400
TI  - Microbacterium hydrothermale sp. nov., an actinobacterium isolated from
      hydrothermal sediment.
AB  - A Gram-stain-positive, aerobic, non-motile, rod-shaped bacterium, strain 0704C9
      2(T), was isolated from hydrothermal sediment of the Indian Ocean. The organism
      grew with 0-5% (w/v) NaCl and at 10-37  degrees C, with optimal growth occurring
      with 1% NaCl and at 28-30  degrees C. Comparative 16S rRNA gene sequence analysis
      revealed that strain 0704C9-2(T) belonged to the genus Microbacterium. It
      exhibited highest 16S rRNA gene sequence similarity with Microbacterium testaceum
      DSM 20166(T) (98.4%). Levels of similarity with the type strains of all other
      recognized species of the genus Microbacterium were less than 98.0%. DNA-DNA
      hybridization experiments with strain 0704C9-2(T) and its closest relative, M.
      testaceum DSM 20166(T), revealed a low reassociation value of 42.9%. The DNA G+C
      content of strain 0704C9-2(T) was 73.3 mol%. The cell-wall peptidoglycan
      contained ornithine and the acyl type was glycolyl. The major whole-cell sugars
      were mannose, galactose, rhamnose and glucose. The major cellular fatty acids
      were anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0. The predominant
      menaquinones were MK-11, MK-10 and MK-12. The major polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol, two unknown glycolipids and an
      unknown phospholipid. On the basis of phenotypic, phylogenetic and genotypic
      data, strain 0704C9-2(T) represents a novel species within the genus
      Microbacterium, for which the name Microbacterium hydrothermale sp. nov. is
      proposed. The type strain is 0704C9-2(T) ( = LMG 27542(T) = CGMCC 1.12512(T)).

PMID- 25052401
TI  - Fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome:
      postnatal outcomes of the first 100 patients.
AB  - BACKGROUND: Fetal aortic valvuloplasty can be performed for severe midgestation
      aortic stenosis in an attempt to prevent progression to hypoplastic left heart
      syndrome (HLHS). A subset of patients has achieved a biventricular (BV)
      circulation after fetal aortic valvuloplasty. The postnatal outcomes and survival
      of the BV patients, in comparison with those managed as HLHS, have not been
      reported. METHODS AND RESULTS: We included 100 patients who underwent fetal
      aortic valvuloplasty for severe midgestation aortic stenosis with evolving HLHS
      from March 2000 to January 2013. Patients were categorized based on postnatal
      management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses
      were live-born, and 38 had a BV circulation (31 from birth, 7 converted after
      initial univentricular palliation). Left-sided structures, namely aortic and
      mitral valve sizes and left ventricular volume, were significantly larger in the
      BV group at the time of birth (P<0.01). After a median follow-up of 5.4 years,
      freedom from cardiac death among all BV patients was 96+/-4% at 5 years and 84+/
      12% at 10 years, which was better than HLHS patients (log-rank P=0.04). There was
      no cardiac mortality in patients with a BV circulation from birth. All but 1 of
      the BV patients required postnatal intervention; 42% underwent aortic or mitral
      valve replacement. On the most recent echocardiogram, the median left ventricular
      end-diastolic volume z score was +1.7 (range, -1.3 to +8.2), and 80% had normal
      ejection fraction. CONCLUSIONS: Short- and intermediate-term survival among
      patients who underwent fetal aortic valvuloplasty and achieved a BV circulation
      postnatally is encouraging. However, morbidity still exists, and ongoing
      assessment is warranted.

PMID- 25052402
TI  - Hypoplastic left heart syndrome: can we change the rules of the game?

PMID- 25052403
TI  - Sex differences in long-term mortality after myocardial infarction: a systematic
      review.
AB  - BACKGROUND: Studies of sex differences in long-term mortality after acute
      myocardial infarction have reported mixed results. A systematic review is needed
      to characterize what is known about sex differences in long-term outcomes and to
      define gaps in knowledge. METHODS AND RESULTS: We searched the Medline database
      from 1966 to December 2012 to identify all studies that provided sex-based
      comparisons of mortality after acute myocardial infarction. Only studies with at
      least 5 years of follow-up were reviewed. Of the 1877 identified abstracts, 52
      studies met the inclusion criteria, of which 39 were included in this review.
      Most studies included fewer than one-third women. There was significant
      heterogeneity across studies in patient populations, methodology, and risk
      adjustment, which produced substantial variability in risk estimates. In general,
      most studies reported higher unadjusted mortality for women compared with men at
      both 5 and 10 years after acute myocardial infarction; however, many of the
      differences in mortality became attenuated after adjustment for age.
      Multivariable models varied between studies; however, most reported a further
      reduction in sex differences after adjustment for covariates other than age. Few
      studies examined sex-by-age interactions; however, several studies reported
      interactions between sex and treatment whereby women have similar mortality risk
      as men after revascularization. CONCLUSIONS: Sex differences in long-term
      mortality after acute myocardial infarction are largely explained by differences
      in age, comorbidities, and treatment use between women and men. Future research
      should aim to clarify how these differences in risk factors and presentation
      contribute to the sex gap in mortality.

PMID- 25052404
TI  - Sex, death, and the diagnosis gap.

PMID- 25052405
TI  - Wolff-Parkinson-White syndrome in the era of catheter ablation: insights from a
      registry study of 2169 patients.
AB  - BACKGROUND: The management of Wolff-Parkinson-White is based on the distinction
      between asymptomatic and symptomatic presentations, but evidence is limited in
      the asymptomatic population. METHODS AND RESULTS: The Wolff-Parkinson-White
      registry was an 8-year prospective study of either symptomatic or asymptomatic
      Wolff-Parkinson-White patients referred to our Arrhythmology Department for
      evaluation or ablation. Inclusion criteria were a baseline electrophysiological
      testing with or without radiofrequency catheter ablation (RFA). Primary end
      points were the percentage of patients who experienced ventricular fibrillation
      (VF) or potentially malignant arrhythmias and risk factors. Among 2169 enrolled
      patients, 1001 (550 asymptomatic) did not undergo RFA (no-RFA group) and 1168
      (206 asymptomatic) underwent ablation (RFA group). There were no differences in
      clinical and electrophysiological characteristics between the 2 groups except for
      symptoms. In the no-RFA group, VF occurred in 1.5% of patients, virtually
      exclusively (13 of 15) in children (median age, 11 years), and was associated
      with a short accessory pathway antegrade refractory period (P<0.001) and
      atrioventricular reentrant tachycardia initiating atrial fibrillation (P<0.001)
      but not symptoms. In the RFA group, ablation was successful in 98.5%, and after
      RFA, no patients developed malignant arrhythmias or VF over the 8-year follow-up.
      Untreated patients were more likely to experience malignant arrhythmias and VF
      (log-rank P<0.001). Time-dependent receiver-operating characteristic curves for
      predicting VF identified an optimal anterograde effective refractory period of
      the accessory pathway cutoff of 240 milliseconds. CONCLUSIONS: The prognosis of
      the Wolff-Parkinson-White syndrome essentially depends on intrinsic
      electrophysiological properties of AP rather than on symptoms. RFA performed
      during the same procedure after electrophysiological testing is of benefit in
      improving the long-term outcomes.

PMID- 25052406
TI  - The asymptomatic Wolff-Parkinson-White patient: time to be more proactive?

PMID- 25052407
TI  - FDG PET/CT imaging in prostate adenocarcinoma presenting as isolated brain
      metastases of unknown origin.

PMID- 25052408
TI  - Rab17-mediated recycling endosomes contribute to autophagosome formation in
      response to Group A Streptococcus invasion.
AB  - Autophagy plays a crucial role in host defence by facilitating the degradation of
      invading bacteria such as Group A Streptococcus (GAS). GAS-containing
      autophagosome-like vacuoles (GcAVs) form when GAS-targeting autophagic membranes
      entrap invading bacteria. However, the membrane origin and the precise molecular
      mechanism that underlies GcAV formation remain unclear. In this study, we found
      that Rab17 mediates the supply of membrane from recycling endosomes (REs) to
      GcAVs. We showed that GcAVs contain the RE marker transferrin receptor (TfR).
      Colocalization analyses demonstrated that Rab17 colocalized effectively with
      GcAV. Rab17 and TfR were visible as punctate structures attached to GcAVs and the
      Rab17-positive dots were recruited to the GAS-capturing membrane. Overexpression
      of Rab17 increased the TfR-positive GcAV content, whereas expression of the
      dominant-negative Rab17 form (Rab17 N132I) caused a decrease, thereby suggesting
      the involvement of Rab17 in RE-GcAV fusion. The efficiency of GcAV formation was
      lower in Rab17 N132I-overexpressing cells. Furthermore, knockdown of Rabex-5, the
      upstream activator of Rab17, reduced the GcAV formation efficiency. These results
      suggest that Rab17 and Rab17-mediated REs are involved in GcAV formation. This
      newly identified function of Rab17 in supplying membrane from REs to GcAVs
      demonstrates that RE functions as a primary membrane source during antibacterial
      autophagy.

PMID- 25052409
TI  - Exploring the potential benefits of vaccinia virus complement control protein in
      controlling complement activation in pathogenesis of the central nervous system
      diseases.
AB  - Aging is a major risk factor for the development of diseases related to the
      central nervous system (CNS), such as Alzheimer's disease (AD) and age-related
      macular degeneration (AMD). In both cases, linkage studies and genome-wide
      association studies found strong links with complement regulatory genes and
      disease risk. In AD, both CLU and CR1 genes were implicated in the late-onset
      form of the disease. In AMD, polymorphisms in CFH, CFB and C2 were similarly
      implicated. The cost of caring for patients with AD or AMD is approaching
      billions of dollars, and with the baby boomers reaching their 60's, this amount
      is likely to increase further. Intervention using complement inhibitors for
      individuals in their early 50s who are at a higher risk of disease development,
      (testing positive for genetic risk factors), could slow the progression of AD or
      AMD and possibly prevent the severity of late stage symptoms. Although we have
      used the vaccinia virus complement control protein (VCP) to elucidate the role of
      complement in CNS diseases, it has merely been an investigational tool but not
      the only possible potential therapeutic agent. 

PMID- 25052410
TI  - Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and
      pyridoxal are prodrugs.
AB  - Vitamin B6 has been known to possess antiemetic effects since 1942. This water
      soluble compound has several forms in the circulation including pyridoxine,
      pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is
      unknown. This was a pre-specified substudy of a randomized, placebo-controlled
      trial comparing the antiemetic effect of the doxylamine-vitamin B6 combination
      (Diclectin(r)) (n = 131) to placebo (n = 126) in women with nausea and vomiting
      of pregnancy. Serum concentrations of pyridoxine, pyridoxal, and pyridoxal 5'
      phosphate (PLP) and doxylamine were measured on Days 4, 8, and 15. With
      Diclectin(r) exhibiting a significant antiemetic effect in pregnancy, serum
      concentrations of pyridoxine were unmeasurable in almost all patients and those
      of pyridoxal were undetectable in half of patients. In contrast, PLP was
      measurable at sustained, stable steady-state levels in all patients. Our data
      suggest that there is a correlation between PLP levels and PUQE score of morning
      sickness symptoms when pyridoxine and pyridoxal levels are undetectable, and
      hence they might be prodrugs of PLP, which may be the active antiemetic form of
      vitamin B6. 

PMID- 25052411
TI  - Foot-and-mouth Disease Transmission in Africa: Implications for Control, a
      Review.
AB  - In Africa, for the control of foot-and-mouth disease (FMD), more information is
      needed on the spread of the disease at local, regional and inter-regional level.
      The aim of this review is to identify the role that animal husbandry, trade and
      wildlife have on the transmission of FMD and to provide a scientific basis for
      different FMD control measures in Africa. Review of literature, published reports
      and databases shows that there is more long distance spread of FMD virus
      serotypes within North, West, Central and East Africa than in southern Africa. In
      North, West, Central and East Africa migratory animal husbandry systems often
      related with search for grazing and water as well as trade are practiced to a
      greater extent than in southern Africa. In southern Africa, the role of African
      buffalo (Syncerus caffer) is more extensively studied than in the other parts of
      Africa, but based on the densities of African buffalo in Central and East Africa,
      one would assume that buffalo should also play a role in the epidemiology of FMD
      in this part of Africa. More sampling of buffalo is necessary in West, Central
      and East Africa. The genetic analysis of virus strains has proven to be valuable
      to increase our understanding in the spread of FMD in Africa. This review shows
      that there is a difference in FMD occurrence between southern Africa and the rest
      of the continent; this distinction is most likely based on differences in animal
      husbandry and trade systems. Insufficient data on FMD in wildlife outside
      southern Africa is limiting our understanding on the role wildlife plays in the
      transmission of FMD in the other buffalo inhabited areas of Africa. 

PMID- 25052412
TI  - Isolation-by-distance in landscapes: considerations for landscape genetics.
AB  - In landscape genetics, isolation-by-distance (IBD) is regarded as a baseline
      pattern that is obtained without additional effects of landscape elements on gene
      flow. However, the configuration of suitable habitat patches determines deme
      topology, which in turn should affect rates of gene flow. IBD patterns can be
      characterized either by monotonically increasing pairwise genetic differentiation
      (for example, FST) with increasing interdeme geographic distance (case-I pattern)
      or by monotonically increasing pairwise genetic differentiation up to a certain
      geographical distance beyond which no correlation is detectable anymore (case-IV
      pattern). We investigated if landscape configuration influenced the rate at which
      a case-IV pattern changed to a case-I pattern. We also determined at what
      interdeme distance the highest correlation was measured between genetic
      differentiation and geographic distance and whether this distance corresponded to
      the maximum migration distance. We set up a population genetic simulation study
      and assessed the development of IBD patterns for several habitat configurations
      and maximum migration distances. We show that the rate and likelihood of the
      transition of case-IV to case-I FST-distance relationships was strongly
      influenced by habitat configuration and maximum migration distance. We also found
      that the maximum correlation between genetic differentiation and geographic
      distance was not related to the maximum migration distance and was measured
      across all deme pairs in a case-I pattern and, for a case-IV pattern, at the
      distance where the FST-distance curve flattens out. We argue that in landscape
      genetics, separate analyses should be performed to either assess IBD or the
      landscape effects on gene flow.

PMID- 25052413
TI  - Maternal telomere length inheritance in the king penguin.
AB  - Telomeres are emerging as a biomarker for ageing and survival, and are likely
      important in shaping life-history trade-offs. In particular, telomere length with
      which one starts in life has been linked to lifelong survival, suggesting that
      early telomere dynamics are somehow related to life-history trajectories. This
      result highlights the importance of determining the extent to which telomere
      length is inherited, as a crucial factor determining early life telomere length.
      Given the scarcity of species for which telomere length inheritance has been
      studied, it is pressing to assess the generality of telomere length inheritance
      patterns. Further, information on how this pattern changes over the course of
      growth in individuals living under natural conditions should provide some insight
      on the extent to which environmental constraints also shape telomere dynamics. To
      fill this gap partly, we followed telomere inheritance in a population of king
      penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence
      on chick initial telomere length (10 days old after hatching), and how these
      relationships changed with chick age (at 70, 200 and 300 days old). Based on a
      correlative approach, offspring telomere length was positively associated with
      maternal telomere length early in life (at 10 days old). However, this
      relationship was not significant at older ages. These data suggest that telomere
      length in birds is maternally inherited. Nonetheless, the influence of
      environmental conditions during growth remained an important factor shaping
      telomere length, as the maternal link disappeared with chicks' age.

PMID- 25052414
TI  - Genetic reincarnation of workers as queens in the Eastern honeybee Apis cerana.
AB  - Thelytokous parthenogenesis, or the asexual production of female offspring, is
      rare in the animal kingdom, but relatively common in social Hymenoptera. However,
      in honeybees, it is only known to be ubiquitous in one subspecies of Apis
      mellifera, the Cape honeybee, A. mellifera capensis. Here we report the
      appearance of queen cells in two colonies of the Eastern honeybee Apis cerana
      that no longer contained a queen or queen-produced brood to rear queens from. A
      combination of microsatellite genotyping and the timing of the appearance of
      these individuals excluded the possibility that they had been laid by the
      original queen. Based on the genotypes of these individuals, thelytokous
      production by natal workers is the most parsimonious explanation for their
      existence. Thus, we present the first example of thelytoky in a honeybee outside
      A. mellifera. We discuss the evolutionary and ecological consequences of
      thelytoky in A. cerana, in particular the role thelytoky may play in the recent
      invasions by populations of this species.

PMID- 25052415
TI  - Phylogenomics of the killer whale indicates ecotype divergence in sympatry.
AB  - For many highly mobile species, the marine environment presents few obvious
      barriers to gene flow. Even so, there is considerable diversity within and among
      species, referred to by some as the 'marine speciation paradox'. The recent and
      diverse radiation of delphinid cetaceans (dolphins) represents a good example of
      this. Delphinids are capable of extensive dispersion and yet many show fine-scale
      genetic differentiation among populations. Proposed mechanisms include the
      division and isolation of populations based on habitat dependence and resource
      specializations, and habitat release or changing dispersal corridors during
      glacial cycles. Here we use a phylogenomic approach to investigate the origin of
      differentiated sympatric populations of killer whales (Orcinus orca). Killer
      whales show strong specialization on prey choice in populations of stable
      matrifocal social groups (ecotypes), associated with genetic and phenotypic
      differentiation. Our data suggest evolution in sympatry among populations of
      resource specialists.

PMID- 25052416
TI  - Introgression study reveals two quantitative trait loci involved in interspecific
      variation in memory retention among Nasonia wasp species.
AB  - Genes involved in the process of memory formation have been studied intensively
      in model organisms; however, little is known about the mechanisms that are
      responsible for natural variation in memory dynamics. There is substantial
      variation in memory retention among closely related species in the parasitic wasp
      genus Nasonia. After a single olfactory conditioning trial, N. vitripennis
      consolidates long-term memory that lasts at least 6 days. Memory of the closely
      related species N. giraulti is present at 24 h but is lost within 2 days after a
      single trial. The genetic basis of this interspecific difference in memory
      retention was studied in a backcrossing experiment in which the phenotype of N.
      giraulti was selected for in the background of N. vitripennis for up to five
      generations. A genotyping microarray revealed five regions that were retained in
      wasps with decreased memory retention. Independent introgressions of individual
      candidate regions were created using linked molecular markers and tested for
      memory retention. One region on chromosome 1 (spanning ~5.8 cM) and another on
      chromosome 5 (spanning ~25.6 cM) resulted in decreased memory after 72 h, without
      affecting 24-h-memory retention. This phenotype was observed in both heterozygous
      and homozygous individuals. Transcription factor CCAAT/enhancer-binding protein
      and a dopamine receptor, both with a known function in memory formation, are
      within these genomic regions and are candidates for the regulation of memory
      retention. Concluding, this study demonstrates a powerful approach to study
      variation in memory retention and provides a basis for future research on its
      genetic basis.

PMID- 25052417
TI  - The efficiency of close inbreeding to reduce genetic adaptation to captivity.
AB  - Although ex situ conservation is indispensable for thousands of species, captive
      breeding is associated with negative genetic changes: loss of genetic variance
      and genetic adaptation to captivity that is deleterious in the wild. We used
      quantitative genetic individual-based simulations to model the effect of genetic
      management on the evolution of a quantitative trait and the associated fitness of
      wild-born individuals that are brought to captivity. We also examined the
      feasibility of the breeding strategies under a scenario of a large number of loci
      subject to deleterious mutations. We compared two breeding strategies: repeated
      half-sib mating and a method of minimizing mean coancestry (referred to as
      gc/mc). Our major finding was that half-sib mating is more effective in reducing
      genetic adaptation to captivity than the gc/mc method. Moreover, half-sib mating
      retains larger allelic and adaptive genetic variance. Relative to initial
      standing variation, the additive variance of the quantitative trait increased
      under half-sib mating during the sojourn in captivity. Although fragmentation
      into smaller populations improves the efficiency of the gc/mc method, half-sib
      mating still performs better in the scenarios tested. Half-sib mating shows two
      caveats that could mitigate its beneficial effects: low heterozygosity and high
      risk of extinction when populations are of low fecundity and size and one of the
      following conditions are met: (i) the strength of selection in captivity is
      comparable with that in the wild, (ii) deleterious mutations are numerous and
      only slightly deleterious. Experimental validation of half-sib mating is
      therefore needed for the advancement of captive breeding programs.

PMID- 25052418
TI  - Incremental value of natriuretic peptide measurement in acute decompensated heart
      failure (ADHF): a systematic review.
AB  - The aim of this systematic review was to determine whether B-type natriuretic
      peptide (BNP) and N-terminal proBNP (NT-proBNP) independently add incremental
      value for predicting mortality and morbidity in patients with acute decompensated
      heart failure (ADHF). Medline((r)), EmbaseTM, AMED, Cochrane Central Register of
      Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL were
      searched from 1989 to June 2012. We also searched reference lists of included
      articles, systematic reviews, and the gray literature. Studies were screened for
      eligibility criteria and assessed for risk of bias. Data were extracted on study
      design, population demographics, assay cutpoints, prognostic risk prediction
      model covariates, statistical methods, outcomes, and results. From 183 citations,
      only seven studies (5 BNP and 2 NT-proBNP) considered incremental value in ADHF
      subjects admitted to acute care centers. Admission assay levels and length of
      follow-up varied for BNP studies (31 days to 12 months) and for NT-proBNP studies
      (25-82 months). All studies presented at least one estimate of incremental value
      of BNP/NT-proBNP relative to the base prognostic model. Using discrimination or
      likelihood statistics, these studies consistently showed that BNP or NT-proBNP
      increased model performance. Three studies used reclassification and model
      validation computations to establish incremental value; these studies showed less
      consistency with respect to added value. In conclusion, the literature assessing
      incremental value of BNP/NT-proBNP in ADHF populations is limited to seven
      studies evaluating only mortality outcomes and at moderate risk of bias. Although
      there were differences in the base risk prediction models, assay cutpoints, and
      lengths of follow-up, there was consistency in BNP/NT-proBNP adding incremental
      value in prediction models in ADHF patients. 

PMID- 25052419
TI  - Prediction of clinical outcomes using B-type natriuretic peptides in the general
      population: a systematic review.
AB  - The use of B-type natriuretic peptides to predict outcomes in general populations
      has been investigated in a number of primary studies. A previous systematic
      review considering natriuretic peptides in cardiovascular disease included a
      subgroup of general population studies, which suggested an association with a
      number of clinical outcomes. We electronically searched Medline, Embase, AMED,
      Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic
      Reviews, and CINAHL for English-language articles published between 1989 and mid
      2012. We utilized trained reviewers and standardized forms to screen articles for
      inclusion and extract data from included articles. All included studies (n = 7)
      were summarized in narrative and tabular form. A general population was defined
      as one that was randomly selected from a community setting where no specific
      inclusion or exclusion criteria were specified. The seven included studies all
      used FDA approved assays for NT-proBNP. The range of clinical outcomes and
      heterogeneity did not allow for meta-analysis. The hazard ratios for predicting
      outcomes in the included studies ranged from 1.0 to 4.1 (all p values <0.05). The
      discrimination statistics reported in four studies all demonstrated statistically
      significant improvements in predicting outcomes. NT-proBNP is associated with
      heart failure, all-cause and cardiovascular mortality, and other combined
      cardiovascular events in a general unselected population. The discrimination
      statistics suggest modest improvements in risk stratification. No prospective
      studies exist to demonstrate the clinical utility of using B-type natriuretic
      peptides to predict clinical outcomes in a general population. 

PMID- 25052421
TI  - G-computation might be used to control for confounding when estimating the
      population-level impact of interventions through outcome distribution curves.

PMID- 25052420
TI  - Feasibility and pilot study of the effects of microfinance on mortality and
      nutrition in children under five amongst the very poor in India: study protocol
      for a cluster randomized controlled trial.
AB  - BACKGROUND: The United Nations Millennium Development Goals include targets for
      the health of children under five years old. Poor health is linked to poverty and
      microfinance initiatives are economic interventions that may improve health by
      breaking the cycle of poverty. However, there is a lack of reliable evidence to
      support this. In addition, microfinance schemes may have adverse effects on
      health, for example due to increased indebtedness. Rojiroti UK and the Centre for
      Promoting Sustainable Livelihood run an innovative microfinance scheme that
      provides microcredit via women's self-help groups (SHGs). This pilot study,
      conducted in rural Bihar (India), will establish whether it is feasible to
      collect anthropometric and mortality data on children under five years old and to
      conduct a limited cluster randomized trial of the Rojiroti intervention.
      METHODS/DESIGN: We have designed a cluster randomized trial in which
      participating tolas (small communities within villages) will be randomized to
      either receive early (SHGs and microfinance at baseline) or late intervention
      (SHGs and microfinance after 18 months). Using predesigned questionnaires,
      demographic, and mortality data for the last year and information about
      participating mothers and their children will be collected and the weight,
      height, and mid upper arm circumference (MUAC) of children will be measured at
      baseline and at 18 months. The late intervention group will establish SHGs and
      microfinance support at this point and data collection will be repeated at 36
      months.The primary outcome measure will be the mean weight for height z-score of
      children under five years old in the early and late intervention tolas at 18
      months. Secondary outcome measures will be the mortality rate, mean weight for
      age, height for age, prevalence of underweight, stunting, and wasting among
      children under five years of age. DISCUSSION: Despite economic progress, marked
      inequalities in child health persist in India and Bihar is one of the worst
      affected states. There is a need to evaluate programs that may alleviate poverty
      and improve health. This study will help to inform the design of a definitive
      trial to determine if the Rojiroti scheme can improve the nutrition and survival
      of children under five years of age in deprived rural communities. TRIAL
      REGISTRATION: Clinicaltrials.gov (study ID: NCT01845545). Registered on 24 April
      2013.

PMID- 25052422
TI  - A convergent rhodium-catalysed asymmetric synthesis of tetrahydroquinolines.
AB  - Rh-catalysed conjugate additions of 2-aminophenyl boronic acid derivatives were
      exploited in diastereoselective and asymmetric syntheses of tetrahydroquinolines.
      In both cases, combinatorial variation of the substitution of the
      tetrahydroquinoline ring system was possible. 

PMID- 25052423
TI  - Bilateral optic neuropathy with bilateral putaminal lesions: a case report.
AB  - Bilateral optic neuropathy with bilateral putaminal lesions may be caused by
      methanol or cyanide poisoning or mitochondrial disorders including Leber
      hereditary optic neuropathy and Leigh syndrome. We report the case of a 34-year
      old Japanese man who developed bilateral visual loss 5 days after the development
      of gastrointestinal symptoms. Magnetic resonance imaging of the brain on
      admission revealed high-intensity signal areas in the bilateral putamina on
      diffusion-weighted and T2-weighted images as well as a high-intensity signal area
      in the left middle cerebellar peduncle that had been identified 3 years
      previously. We diagnosed bilateral optic neuropathy with bilateral putaminal
      lesions caused by preceding infection-triggered demyelination. We administered
      methylprednisolone, but his vision did not recover. 

PMID- 25052425
TI  - Scientific writing: strategies and tools for students and advisors.
AB  - Scientific writing is a demanding task and many students need more time than
      expected to finish their research articles. To speed up the process, we highlight
      some tools, strategies as well as writing guides. We recommend starting early in
      the research process with writing and to prepare research articles, not after but
      in parallel to the lab or field work. We suggest considering scientific writing
      as a team enterprise, which needs proper organization and regular feedback. In
      addition, it is helpful to select potential target journals early and to consider
      not only scope and reputation, but also decision times and rejection rates.
      Before submission, instructions to authors and writing guides should be
      considered, and drafts should be extensively revised. Later in the process
      editor's and reviewer's comments should be followed. Our tips and tools help
      students and advisors to structure the writing and publishing process, thereby
      stimulating them to develop their own strategies to success.

PMID- 25052424
TI  - Cryptochrome-dependent magnetic field effect on seizure response in Drosophila
      larvae.
AB  - The mechanisms that facilitate animal magnetoreception have both fascinated and
      confounded scientists for decades, and its precise biophysical origin remains
      unclear. Among the proposed primary magnetic sensors is the flavoprotein,
      cryptochrome, which is thought to provide geomagnetic information via a quantum
      effect in a light-initiated radical pair reaction. Despite recent advances in the
      radical pair model of magnetoreception from theoretical, molecular and animal
      behaviour studies, very little is known of a possible signal transduction
      mechanism. We report a substantial effect of magnetic field exposure on seizure
      response in Drosophila larvae. The effect is dependent on cryptochrome, the
      presence and wavelength of light and is blocked by prior ingestion of typical
      antiepileptic drugs. These data are consistent with a magnetically-sensitive,
      photochemical radical pair reaction in cryptochrome that alters levels of
      neuronal excitation, and represent a vital step forward in our understanding of
      the signal transduction mechanism involved in animal magnetoreception. 

PMID- 25052426
TI  - Bahamaolide A from the marine-derived Streptomyces sp. CNQ343 inhibits isocitrate
      lyase in Candida albicans.
AB  - Bahamaolide A, a new macrocyclic lactone isolated from the culture of marine
      actinomycete Streptomyces sp. CNQ343, was evaluated for its inhibitory activity
      toward isocitrate lyase (ICL) from Candida albicans. These studies led to the
      identification of bahamaolide A as a potent ICL inhibitor with IC50 value of
      11.82 MUM. The growth phenotype of ICL deletion mutants and quantitative RT-PCR
      analyses indicated that this compound inhibits the ICL mRNA expression in C.
      albicans under C2-carbon-utilizing conditions. The present data highlight the
      potential for bahamaolide A treatment of C. albicans infections via inhibition of
      ICL activity.

PMID- 25052427
TI  - The use of spirocyclic scaffolds in drug discovery.
AB  - Owing to their inherent three-dimensionality and structural novelty, spiro
      scaffolds have been increasingly utilized in drug discovery. In this brief
      review, we highlight selected examples from the primary medicinal chemistry
      literature during the last three years to demonstrate the versatility of spiro
      scaffolds. With recent progress in synthetic methods providing access to spiro
      building blocks, spiro scaffolds are likely to be used more frequently in drug
      discovery. 

PMID- 25052428
TI  - Allosteric modulation of the G protein-coupled US28 receptor of human
      cytomegalovirus: are the small-weight inverse agonist of US28 'camouflaged'
      agonists?
AB  - The highly constitutively active G protein-coupled receptor US28 of human
      cytomegalovirus (HCMV) is thought to camouflage agonism by mediating constitutive
      endocytosis. With the use of the US28Delta300 mutant, which is largely devoid of
      constitutive internalization, I have demonstrated that the coupling of the
      receptor to its downstream signaling partners is responsible for the inverse
      agonism to agonism efficacy switch in some small-weight ligands of US28. 

PMID- 25052429
TI  - Tibolone prevents oxidation and ameliorates cholinergic deficit induced by ozone
      exposure in the male rat hippocampus.
AB  - Oxidative stress is related to the development of central nervous system diseases
      involving memory processes. Cholinergic system and memory processes are disrupted
      by ozone exposure. In rats, ozone induces motor disturbances and memory deficits
      as well as biochemical changes in brain regions related to memory processes. In
      this work, we analyzed the effect of chronic tibolone (TIB) administration in
      central nervous system, specifically the content of choline acetyltransferase,
      acetylcholinesterase, acetylcholine and oxidative stress markers in the
      hippocampus of male rats exposed to ozone. Our results reveal a neuroprotective
      effect of TIB treatment on neuronal damage induced by chronic ozone exposure.
      Furthermore, we suggest that TIB can prevent memory deficits by providing a
      protective effect against oxidative stress and the cholinergic system disruption
      induced by ozone exposure. Together, these findings present a potential
      neuroprotective effect of TIB in processes linked to memory deficits induced by
      aging or neurodegenerative diseases. 

PMID- 25052430
TI  - CoCl2-induced biochemical hypoxia down regulates activities and expression of
      super oxide dismutase and catalase in cerebral cortex of mice.
AB  - Hypoxia-induced oxidative stress is one of the major hallmark reasons underlying
      brain dysfunction. In the present manuscript, we have used CoCl2-induced hypoxic
      mice to investigate alterations in the activities of chief antioxidative stress
      enzymes- superoxide dismutase (SOD) and catalase (CAT) and expression of their
      genes Sod1 and Cat in the cerebral cortex as this model has not been routinely
      used for carrying out such study. Hypoxia mimetic mice model was accordingly
      developed by oral CoCl2 administration to mice and validated by analyzing
      alterations in the expression of the hypoxia inducible factor gene Hif-1alpha and
      its immediate responsive genes. Our Western blot data demonstrated that a dose of
      40 mg/kg BW of CoCl2 was able to generate hypoxia like condition in mice in which
      Hif-1alpha and its immediate responsive genes-glutamate transporter-1 (Slc2a1)
      and erythropoietin (Epo) expression were up regulated. Our in-gel assay data
      indicated that SOD and CAT activities significantly declined and it was
      associated with significant down regulation of Sod1 and Epo expression as evident
      from our semi quantitative RT-PCR and Western blot data, which might be
      correlated with up regulation of Hif-1alpha expression in the cerebral cortex of
      the CoCl2-treated hypoxic mice. Our findings suggest that CoCl2-induced hypoxic
      mouse model is useful for studying alterations in the anti oxidative enzymes and
      biochemical/molecular/neurobiological analysis of hypoxia-induced alterations in
      brain function.

PMID- 25052431
TI  - Medical teachers conceptualize a distinctive form of clinical knowledge.
AB  - For over four decades, there have been efforts to specify the types of knowledge
      that medical students need, how that knowledge is acquired and how its
      constituent parts are related. It is one of the areas of continuing concern
      underlying medical education reform. Despite their importance to medical
      students' learning and development, the perspectives of medical teachers in
      hospitals are not always considered in such discourse. This study sought to
      generate an understanding of these teachers' values, perspectives and approaches
      by listening to them and seeing them in their everyday teaching work, finding and
      understanding the meanings they bring to the work of medical teaching in
      hospitals. In interviews, all of the teachers talked more about the optimal forms
      of knowledge that are important for students than they talked about the form of
      the teaching itself. Many revealed to students what knowledge they do and do not
      value. They had a particular way of thinking about clinical knowledge as existing
      in the people and the places in which the teaching and the clinical practice
      happen, and represented this as 'real' knowledge. By implication, there is other
      knowledge in medical education or in students' heads that is not real and needs
      to be transformed. Their values, practices and passions add texture and vitality
      to existing ways of thinking about the characteristics of clinical knowledge, how
      it is depicted in the discourse and the curriculum and how it is more dynamically
      related to other knowledge than is suggested in traditional conceptualizations of
      knowledge relationships.

PMID- 25052435
TI  - Estimation of genetic and crossbreeding parameters of fatty acid concentrations
      in milk fat predicted by mid-infrared spectroscopy in New Zealand dairy cattle.
AB  - The objective of this study was to estimate heritability and crossbreeding
      parameters (breed and heterosis effects) of various fatty acid (FA)
      concentrations in milk fat of New Zealand dairy cattle. For this purpose,
      calibration equations to predict concentration of each of the most common FAs
      were derived with partial least squares (PLS) using mid-infrared (MIR) spectral
      data from milk samples (n=850) collected in the 2003-04 season from 348 second
      parity crossbred cows during peak, mid and late lactation. The milk samples
      produced both, MIR spectral data and concentration of the most common FAs
      determined using gas chromatography (GC). The concordance correlation
      coefficients (CCC) between the concentration of a FA determined by GC and the PLS
      equation ranged from 0.63 to 0.94, suggesting that some prediction equations can
      be considered to have substantial predictive ability. The PLS calibration
      equations were then used to predict the concentration of each of the fatty acids
      in 26,769 milk samples from 7385 cows that were herd-tested during the 2007-08
      season. Data were analysed using a single-trait repeatability animal model.
      Shorter chain FA (16:0 and below) were significantly higher (P<0.05) in Jersey
      cows, while longer chain, including unsaturated longer chain FA were higher in
      Holstein-Friesian cows. The estimates of heritabilities ranged from 0.17 to 0.41
      suggesting that selective breeding could be used to ensure milk fat composition
      stays aligned to consumer, market and manufacturing needs.

PMID- 25052433
TI  - Selecting long-term care facilities with high use of acute hospitalisations:
      issues and options.
AB  - BACKGROUND: This paper considers approaches to the question "Which long-term care
      facilities have residents with high use of acute hospitalisations?" It compares
      four methods of identifying long-term care facilities with high use of acute
      hospitalisations by demonstrating four selection methods, identifies key factors
      to be resolved when deciding which methods to employ, and discusses their
      appropriateness for different research questions. METHODS: OPAL was a census-type
      survey of aged care facilities and residents in Auckland, New Zealand, in 2008.
      It collected information about facility management and resident demographics,
      needs and care. Survey records (149 aged care facilities, 6271 residents) were
      linked to hospital and mortality records routinely assembled by health
      authorities. The main ranking endpoint was acute hospitalisations for diagnoses
      that were classified as potentially avoidable. Facilities were ranked using 1)
      simple event counts per person, 2) event rates per year of resident follow-up, 3)
      statistical model of rates using four predictors, and 4) change in ranks between
      methods 2) and 3). A generalized mixed model was used for Method 3 to handle the
      clustered nature of the data. RESULTS: 3048 potentially avoidable
      hospitalisations were observed during 22 months' follow-up. The same "top ten"
      facilities were selected by Methods 1 and 2. The statistical model (Method 3),
      predicting rates from resident and facility characteristics, ranked facilities
      differently than these two simple methods. The change-in-ranks method identified
      a very different set of "top ten" facilities. All methods showed a continuum of
      use, with no clear distinction between facilities with higher use. CONCLUSION:
      Choice of selection method should depend upon the purpose of selection. To
      monitor performance during a period of change, a recent simple rate, count per
      resident, or even count per bed, may suffice. To find high-use facilities
      regardless of resident needs, recent history of admissions is highly predictive.
      To target a few high-use facilities that have high rates after considering
      facility and resident characteristics, model residuals or a large increase in
      rank may be preferable.

PMID- 25052436
TI  - Milk metabolites as indicators of mammary gland functions and milk quality.
AB  - The assumption, that metabolites derived from the activity of the mammary gland
      epithelial cells reflect changes in milk secretion and its coagulation
      properties, was tested in dairy cows. The experiment included cows with
      uninfected udders and cows with one of the glands infected by different bacteria
      specie. Analysis were carried at the cow level (including all four glands), or at
      the gland level. High and significant correlations among the concentrations of
      lactose, glucose, glucose-6-posphate, milk related respiratory index (the ratio
      between the concentrations of citrate/lactate+malate in milk) and milk-derived
      glycolytic index (the ratio between glucose-6-phosphate and glucose in milk) and
      milk clotting parameters were found. The physiological basis for these relations
      and their ability to predict the deterioration in milk quality in subclinically
      infected glands and in glands previously clinically infected with Escherichia
      coli are discussed. 

PMID- 25052437
TI  - Process optimisation for preparation of caseinophosphopeptides from buffalo milk
      casein and their characterisation.
AB  - Caseinophosphopeptides (CPPs) are multifunctional bioactive peptides containing
      phosphorylated seryl residues in their sequence. In the present study, method for
      the production of CPPs from buffalo milk casein was optimised and characterised
      for their sequence, calcium solubilising and calcium binding activities. Response
      surface methodology was used to optimise the conditions for hydrolysis of buffalo
      casein by trypsin to obtain maximum yield of CPPs. The optimum hydrolysis
      conditions were as follows: hydrolysis pH 7.5, temperature 37  degrees C,
      hydrolysis time 7.0 h. Under these conditions, the experimental yield obtained
      was 10.04+/-0.24%, which is slightly lower than value predicted by the model.
      These CPPs were able to solubilise 1.03+/-0.08 mg la/mg CPPs in presence of
      excess phosphate and bind 0.935 mg of Ca/mg of CPPs. Eight phosphopeptides, i.e.,
      alpha(s1)-CN f (37-58) 2P; alpha(s1)-CN f (37-58) 3P; alpha(s1)-CN f (35-58) 2P;
      alpha(s1)-CN f (35-58) 3P; alpha(s2)-CN f (2-21) 4P; alpha(s2)-CN f (138-149) 1P;
      beta-CN f (2-28) 4P and beta-CN f (33-48) 1P were identified by LC-MS/MS which
      contained motif for binding of divalent minerals. The sequences of these CPPs
      differed from that of derived from bovine casein.

PMID- 25052438
TI  - Detection of antibiotics in goat's milk: effect of detergents on the response of
      microbial inhibitor tests.
AB  - The aim of the study was to evaluate the interference of acid and alkaline
      detergents employed in the cleaning of milking equipment of caprine dairy farms
      on the performance of microbial tests used in antibiotic control (BRT MRL,
      Delvotest MCS, and Eclipse 100). Eight concentrations of commercial detergents,
      five acid (0-0.25%) and five alkaline (0-1%) were add to antimicrobial-free
      goat's milk to evaluate the detergent effect on the response of microbial
      inhibitor tests. To evaluate the effect of detergents on the detection capability
      of microbial tests two detergents at 0.5 ml/l (one acid and one basic) and eight
      concentrations of four beta-lactam antibiotics (ampicillin, amoxicillin,
      cloxacillin and benzylpenicillin) were used. Milk without detergents was used as
      control. The spiked samples were analysed twelve times by three microbial tests.
      The results showed that the presence of acid detergents did not affect the
      response of microbial tests for any of the concentrations tested. However, at
      concentrations equal to or greater than 2 ml/l alkaline detergents positive
      results were found in microbial tests (16.7-100%). The detection limits of the
      screening tests for penicillins were not modified substantially by the presence
      of detergents. In general, the presence of acid and alkaline detergents in goat's
      milk did not produce a great interference in the microbial tests, only high
      concentrations of detergents could cause non-compliant results, but these
      concentrations are difficult to find in practice if proper cleaning procedures
      are applied in goat dairy farms.

PMID- 25052439
TI  - Enzymatic cross-linking of soy proteins within non-fat set yogurt gel.
AB  - Soy proteins as the health-promoting ingredients and candidate fat substitutes in
      dairy products are good substrates for the cross-linking action of the enzyme
      transglutaminase. Non-fat set yogurt samples were prepared from the milks
      enriched with soy protein isolate (SPI) and/or treated with the enzyme
      transglutaminase. The highest titrable acidity was recorded for the yogurt
      enriched with SPI and treated with the enzyme throughout the cold storage for 21
      d. SPI-enrichment of yogurt milk increased the water holding capacity. Although
      enrichment with SPI did not influence the count of Streptococcus themophilus,
      increased that of Lactobacillus bulgaricus ~3 log cycles. The enzymatic treatment
      of SPI-enriched milk however, suppressed the bacteria growth-promoting influence
      of SPI due probably to making the soy proteins inaccessible for Lactobacillus.
      SPI-enrichment and enzymatic treatment of milk decreased the various organic
      acids content in yoghurt samples; influence of the former was more significant.
      The cross-linking of milk proteins to soy proteins was confirmed with the gel
      electrophoresis results. 

PMID- 25052448
TI  - The roles of influenza virus antigens and the AS03 adjuvant in the 2009 pandemic
      vaccine associated with narcolepsy needs further investigation.

PMID- 25052449
TI  - Suppression of hepatocellular carcinoma development in hepatitis C patients given
      interferon-based antiviral therapy.
AB  - The advance of antiviral treatment for chronic hepatitis C has brought a high
      sustained virological response (SVR) rate. In this review article, the
      suppressive effect of interferon (IFN)-based therapy on the development of
      hepatocellular carcinoma (HCC), risk factors for developing HCC and the
      characteristics of HCC development after SVR among chronic hepatitis C patients
      given IFN-based therapy were studied. The HCC incidence has been revealed to
      decrease with IFN-based antiviral therapy, especially in SVR, and the risk
      factors for developing HCC were older age, advanced liver fibrosis and male sex.
      alpha-Fetoprotein levels at 24 weeks after the end of IFN-based treatment was
      associated strongly with HCC incidence irrespective of virological response. In
      patients with SVR, other risk factors were glucose metabolism disorders, lipid
      metabolism disorders and alcohol intake. Extra attention to the possibility of
      HCC incidence should be required for these SVR patients. Antiviral therapy with a
      combination of HCV-specific direct-acting antivirals (DAA) is expected to be
      utilized in the future. However, it is not known whether DAA-based treatment can
      suppress HCC to the level of IFN-based treatment. Further research is required to
      clarify this. 

PMID- 25052450
TI  - In reply.

PMID- 25052451
TI  - Phase Ib/II trial of gemcitabine, cisplatin, and lenalidomide as first-line
      therapy in patients with metastatic urothelial carcinoma.
AB  - BACKGROUND: Outcomes with current chemotherapy in metastatic urothelial carcinoma
      (MUC) remain poor. Lenalidomide, an antiangiogenic and immunomodulatory agent,
      enhances the effects of chemotherapy in preclinical studies. In this phase Ib/II
      study, we sought to determine a tolerable dose of lenalidomide in combination
      with gemcitabine and cisplatin (GCL) in patients with MUC and to explore the
      safety and activity of this regimen. METHODS: Patients with chemotherapy-naive
      MUC received gemcitabine 1,000 mg/m(2) on days 1 and 8 and cisplatin 70 mg/m(2)
      on day 1 every 21 days. In phase Ib, there were four planned escalating dose
      levels of lenalidomide (10, 15, 20, and 25 mg) daily on days 1-14. RESULTS: Seven
      patients received GCL in phase Ib. The dose of lenalidomide was not escalated
      beyond 10 mg because of cytopenias requiring repeated dose delays and reductions.
      Two additional patients were enrolled in phase II, but the study was ultimately
      terminated due to poor tolerability and slow accrual. The most frequent grade >=
      3 adverse events were cytopenias and diarrhea. Three of the nine patients
      experienced an objective response (one complete response, two partial responses).
      CONCLUSION: Chronic administration of the GCL regimen was poorly tolerated
      because of additive and cumulative myelosuppression.

PMID- 25052452
TI  - Sorafenib in thyroid cancer patients: learning from toxicity.

PMID- 25052453
TI  - Thoraco-abdominal asymmetry and asynchrony in congenital diaphragmatic hernia.
AB  - OBJECTIVE: Congenital diaphragmatic hernia (CDH) consists of an incomplete
      formation of the diaphragm and the subsequent herniation of abdominal bowels.
      Diaphragmatic defect can be repaired by primary closure or placing a patch.
      Respiratory follow up usually focuses on spirometric and clinical evaluation. The
      aim of the study was to assess thoraco-abdominal volumes in CDH patients and to
      verify whether the action of the diaphragm on the chest wall is altered leading
      to an asymmetric and asynchronous expansion of the different thoracoabdominal
      compartments. PATIENTS AND METHODS: Total and compartmental chest wall volumes
      and asynchronies were measured by Opto-Electronic Plethysmography in 14 CDH
      patients (7 M/7F, age 5 +/- 2 years, 12 left side operated) and in 9 age matched
      healthy subjects during quiet spontaneous breathing in supine position. Patients
      were divided in two groups: five patients with suture (group S) and nine patients
      with diaphragmatic patch (group P). Pulmonary function was assessed by spirometry
      and spirometric parameters were expressed as Z-score. RESULTS: In group P
      abdominal contribution to tidal volume was lower than healthy controls and group
      S. Unlike controls, in both CDH groups the right side of pulmonary rib cage moved
      inward with a correspondent left side expansion during inspiration. In group S,
      thoraco-abdominal asynchronies were higher than in group P and controls,
      especially in the right side. Five patients belonging to group P had a
      spirometric obstructive pattern. CONCLUSIONS: In overall CDH patients a reduced
      action of the treated (left) hemi-diaphragm is evident. In patients treated by
      primary suture, a compensatory action of the right side allows to reach a normal
      total diaphragmatic displacement and a proper contribution of the whole diaphragm
      to tidal volume. In patients treated by diaphragmatic patch, instead, thoraco
      abdominal asynchronies are prevented.

PMID- 25052454
TI  - An in situ transmission electron microscopy study of sintering and redispersion
      phenomena over size-selected metal nanoparticles: environmental effects.
AB  - The thermal and chemical stability of micelle-synthesized size-selected Pt
      nanoparticles (NPs) supported on thin SiO2 (20 nm) films was monitored in situ
      via transmission electron microscopy (TEM) under pure hydrogen and pure oxygen
      environments. The coarsening treatment was performed for 30 min at each
      temperature (1 Torr of either O2 or H2), while the TEM measurements were carried
      out at 1 Torr of H2 and 0.5 Torr of O2. Surprisingly, the NPs were found to be
      stable against sintering under both gaseous atmospheres up to 650  degrees C.
      Nevertheless, drastic sintering via diffusion-coalescence was observed upon
      annealing in H2 at 800  degrees C. In contrast, an identically prepared sample
      demonstrated lack of agglomeration at the same temperature under O2. The latter
      observation is ascribed to a strengthened chemical bond at the NP/support
      interface due to the formation of PtOx species at low temperature. Subsequently,
      oxidative NP redispersion - associated with some loss of Pt due to the formation
      of volatile PtOx species - is inferred from the behavior in O2 at/above 650 
      degrees C. In contrast, SiO2 reduction catalyzed by the presence of the Pt NPs
      and Pt silicide formation was found in H2 at 800  degrees C, which might play a
      role in the enhanced coarsening observed. Subsequent exposure of the PtSi NPs to
      oxygen led to the formation of Pt-SiO2 core-shell structures. Our findings
      highlight the dynamic structural transformations that nanoscale materials
      experience under different environments and the important role played by their
      initial size, size distribution and dispersion on their stability against
      sintering. 

PMID- 25052456
TI  - Acute kidney injury in China.
AB  - China has a large population and bears a heavy burden of kidney diseases. Acute
      kidney injury (AKI) is increasingly prevalent in China and is associated with
      severe morbidity and mortality. The inadequacies of early diagnosis and
      management remain the major challenges to Chinese nephrologists. There is an
      urgent need for a nationwide, or even a global effort to increase an awareness of
      the devastating effects of AKI, to develop professional preventive strategies, as
      well as to achieve early diagnosis and early intervention. In this article, we
      review the increasing incidence of AKI and complexity behind prevention and
      management, focusing on differences in various clinical settings in China. 

PMID- 25052457
TI  - Inflammatory myofibroblastic tumour of the central nervous system-inflammation,
      tumour or infection.

PMID- 25052458
TI  - Clinical features and surgical outcomes of intramedullary schwannomas.
AB  - OBJECT: Intramedullary schwannomas are exceedingly rare. Most previous studies
      are case reports with an associated literature review. The aim of this study was
      to discuss the clinical features and the outcomes of microsurgery for these rare
      lesions. METHODS: The authors retrospectively reviewed the data of twenty
      patients with intramedullary schwannomas. All patients had performed preoperative
      and postoperative magnetic resonance imaging (MRI) and underwent microsurgery.
      The diagnosis of intramedullary schwannomas was based on radiological and
      pathological criteria. Modified McCormick classification was applied to assess
      neurological function. RESULTS: There were 15 males and five females with a mean
      age of 44.7 years. Ten tumors were located in the cervical cord, five in the
      thoracic cord, two in the cervicothoracic cord, two in the thoracolumbar cord and
      one in the conus medullaris. Patients presented with nonspecific symptoms and the
      mean duration of symptoms was 37.4 months. Intraoperatively, the tumor was
      connected to the dorsal rootlet in four cases. Gross total resection (GTR) of the
      tumor with a well-demarcated dissection plane was achieved in 16 cases, and
      subtotal resection (STR) was achieved in four cases. No patients received
      postoperative radiotherapy. During a mean follow-up period of 67.9 months, no
      recurrence or regrowth of the residual tumors was observed on MRI. Ninety percent
      of patients experienced an improvement in the McCormick grade and 10 % of
      patients maintained their preoperative status. CONCLUSIONS: Intramedullary
      schwannomas are benign but clinically progressive lesions. The accurate diagnosis
      depends on pathology. For symptomatic patients, early surgery should be performed
      before neurological deficits deteriorate. When GTR cannot be achieved, STR of the
      tumor for decompression is advised. Postoperative radiotherapy is not recommended
      for these benign tumors. A good clinical outcome after GTR or STR can be
      expected.

PMID- 25052459
TI  - Incorporating economic evaluation into immunization decision making in Canada: a
      workshop.

PMID- 25052460
TI  - Criterion validity of the general factor of psychopathology in a prospective
      study of girls.
AB  - BACKGROUND: The best-fitting model of the structure of common psychopathology
      often includes a general factor on which all dimensions of psychopathology load.
      Such a general factor would be important if it reflects etiologies and mechanisms
      shared by all dimensions of psychopathology. Nonetheless, a viable alternative
      explanation is that the general factor is partly or wholly a result of common
      method variance or other systematic measurement biases. METHODS: To test this
      alternative explanation, we extracted general, externalizing, and internalizing
      factor scores using mother-reported symptoms across 5-11 years of age in
      confirmatory factor analyses of data from a representative longitudinal study of
      2,450 girls. Independent associations between the three psychopathology factor
      scores and teacher-reported criterion variables were estimated in multiple
      regression, controlling intelligence, and demographic covariates. RESULTS: The
      model including the general factor fit significantly better than a correlated two
      factor (internalizing/externalizing) model. The general factor was robustly and
      independently associated with all measures of teacher-reported school functioning
      concurrently during childhood and prospectively during adolescence. CONCLUSIONS:
      These findings weaken the hypothesis that the general factor of psychopathology
      in childhood is solely a measurement artifact and support further research on the
      substantive meaning of the general factor.

PMID- 25052461
TI  - Use of a melanoma simulation model in a dermatology objective structured clinical
      examination station.

PMID- 25052462
TI  - Controlling for seasonal patterns and time varying confounders in time-series
      epidemiological models: a simulation study.
AB  - An important topic when estimating the effect of air pollutants on human health
      is choosing the best method to control for seasonal patterns and time varying
      confounders, such as temperature and humidity. Semi-parametric Poisson time
      series models include smooth functions of calendar time and weather effects to
      control for potential confounders. Case-crossover (CC) approaches are considered
      efficient alternatives that control seasonal confounding by design and allow
      inclusion of smooth functions of weather confounders through their equivalent
      Poisson representations. We evaluate both methodological designs with respect to
      seasonal control and compare spline-based approaches, using natural splines and
      penalized splines, and two time-stratified CC approaches. For the spline-based
      methods, we consider fixed degrees of freedom, minimization of the partial
      autocorrelation function, and general cross-validation as smoothing criteria.
      Issues of model misspecification with respect to weather confounding are
      investigated under simulation scenarios, which allow quantifying omitted,
      misspecified, and irrelevant-variable bias. The simulations are based on fully
      parametric mechanisms designed to replicate two datasets with different mortality
      and atmospheric patterns. Overall, minimum partial autocorrelation function
      approaches provide more stable results for high mortality counts and strong
      seasonal trends, whereas natural splines with fixed degrees of freedom perform
      better for low mortality counts and weak seasonal trends followed by the time
      season-stratified CC model, which performs equally well in terms of bias but
      yields higher standard errors.

PMID- 25052463
TI  - Impact of electronic health records on the patient experience in a hospital
      setting.
AB  - BACKGROUND: The impact of electronic health records (EHRs) and their effects on
      optimizing the patient experience has been debated nationally. Currently, there
      is a paucity of data in this area, and existing research offers conflicting
      results. Since 2006, the Assessing Residents' CI-CARE (ARC) program has evaluated
      the physician-patient interaction of resident physicians at University of
      California, Los Angeles (UCLA) Health utilizing a 20-item questionnaire
      administered through facilitator-patient interviews. OBJECTIVE: To evaluate the
      impact of EHR implementation on the patient experience. DESIGN: Retrospective
      cohort study. SETTING: Two academic medical campuses: Ronald Reagan UCLA Medical
      Center and UCLA Medical Center, Santa Monica. METHODS: A total of 3417 surveys,
      spanning December 1, 2012 to May 30, 2013, were assessed. This included patient
      representation from 9 departments within UCLA Health. Surveys were analyzed to
      assess physician-patient communication. Statistical comparisons were made using
      chi analysis. RESULTS: All 16 questions assessing physician-patient communication
      received better responses in the 3 months following EHR implementation, compared
      to the 3 months prior to implementation. Of these, 9 questions illustrated
      statistically significant improvement, whereas the improvement in the remaining 7
      questions was not statistically significant. DISCUSSION: These results suggest
      that EHRs may improve physician-patient communication. The ARC infrastructure
      allowed for observation of this trend; however, future research should aim to
      further validate and understand the etiologies of this improvement.

PMID- 25052464
TI  - Quality indicators as a tool in improving the introduction of new medicines.
AB  - Quality indicators are increasingly used as a tool to achieve safe and quality
      clinical care, cost-effective therapy, for professional learning, remuneration,
      accreditation and financial incentives. A substantial number focus on drug
      therapy but few address the introduction of new medicines even though this is a
      burning issue. The objective was to describe the issues and challenges in
      designing and implementing a transparent indicator framework and evaluation
      protocol for the introduction of new medicines and to provide guidance on how to
      apply quality indicators in the managed entry of new medicines. Quality
      indicators need to be developed early to assess whether new medicines are
      introduced appropriately. A number of key factors need to be addressed when
      developing, applying and evaluating indicators including dimensions of quality,
      suggested testing protocols, potential data sources, key implementation factors
      such as intended and unintended consequences, budget impact and cost
      effectiveness, assuring the involvement of the medical professions, patients and
      the public, and reliable and easy-to-use computerized tools for data collection
      and management. Transparent approaches include the need for any quality
      indicators developed to handle conflict of interests to enhance their validity
      and acceptance. The suggested framework and indicator testing protocol may be
      useful in assessing the applicability of indicators for new medicines and may be
      adapted to healthcare settings worldwide. The suggestions build on existing
      literature to create a field testing methodology that can be used to produce
      country-specific quality indicators for new medicines as well as a cross
      international approach to facilitate access to new medicines. 

PMID- 25052465
TI  - Animal welfare and meat quality: the perspective of Uruguay, a "small" exporter
      country.
AB  - Public sensitivity towards animal welfare has risen in recent years. Uruguay is a
      primary meat exporter. Therefore, it is compulsory not only to provide good
      quality and safe meat, but also to project a welfare friendly image. Uruguayan
      meat production systems are mainly based on rangeland pastures but, due to
      international meat prices and the opening of new markets, intensive fattening
      systems increased. These systems include a wide range of feeding alternatives
      between pasture and concentrate utilization, involving differences in terms of
      animal welfare, carcass and meat quality, that require to be studied.
      Accordingly, some husbandry practices associated mainly with extensive systems
      must be evaluated, as well as their applicability to international
      recommendations related to pre-slaughter handling which may not be suitable for
      local conditions. In the present paper we share scientific results related to the
      impact of different production systems, husbandry practices and pre-slaughter
      procedures associated to animal welfare and meat quality in Uruguayan conditions.

PMID- 25052466
TI  - Identification of microRNAs specific for high producer CHO cell lines using
      steady-state cultivation.
AB  - MicroRNAs are short non-coding RNAs that play an important role in the regulation
      of gene expression. Hence, microRNAs are considered as potential targets for
      engineering of Chinese hamster ovary (CHO) cells to improve recombinant protein
      production. Here, we analyzed and compared the microRNA expression patterns of
      high, low, and non-producing recombinant CHO cell lines expressing two
      structurally different model proteins in order to identify microRNAs that are
      involved in heterologous protein synthesis and secretion and thus might be
      promising targets for cell engineering to increase productivity. To generate
      reproducible and comparable data, the cells were cultivated in a bioreactor under
      steady-state conditions. Global microRNA expression analysis showed that mature
      microRNAs were predominantly upregulated in the producing cell lines compared to
      the non-producer. Several microRNAs were significantly differentially expressed
      between high and low producers, but none of them commonly for both model
      proteins. The identification of target messenger RNAs (mRNAs) is essential to
      understand the biological function of microRNAs. Therefore, we negatively
      correlated microRNA and global mRNA expression data and combined them with
      computationally predicted and experimentally validated targets. However,
      statistical analysis of the identified microRNA-mRNA interactions indicated a
      considerable false positive rate. Our results and the comparison to published
      data suggest that the reaction of CHO cells to the heterologous protein
      expression is strongly product- and/or clone-specific. In addition, this study
      highlights the urgent need for reliable CHO-specific microRNA target prediction
      tools and experimentally validated target databases in order to facilitate
      functional analysis of high-throughput microRNA expression data in CHO cells. 

PMID- 25052467
TI  - Identification of oleaginous yeast strains able to accumulate high intracellular
      lipids when cultivated in alkaline pretreated corn stover.
AB  - Microbial oil is a potential alternative to food/plant-derived biodiesel fuel.
      Our previous screening studies identified a wide range of oleaginous yeast
      species, using a defined laboratory medium known to stimulate lipid accumulation.
      In this study, the ability of these yeasts to grow and accumulate lipids was
      further investigated in synthetic hydrolysate (SynH) and authentic ammonia fiber
      expansion (AFEXTM)-pretreated corn stover hydrolysate (ACSH). Most yeast strains
      tested were able to accumulate lipids in SynH, but only a few were able to grow
      and accumulate lipids in ACSH medium. Cryptococcus humicola UCDFST 10-1004 was
      able to accumulate as high as 15.5 g/L lipids, out of a total of 36 g/L cellular
      biomass when grown in ACSH, with a cellular lipid content of 40 % of cell dry
      weight. This lipid production is among the highest reported values for oleaginous
      yeasts grown in authentic hydrolysate. Preculturing in SynH media with xylose as
      sole carbon source enabled yeasts to assimilate both glucose and xylose more
      efficiently in the subsequent hydrolysate medium. This study demonstrates that
      ACSH is a suitable medium for certain oleaginous yeasts to convert
      lignocellullosic sugars to triacylglycerols for production of biodiesel and other
      valuable oleochemicals.

PMID- 25052468
TI  - New approach for development of sensitive and environmentally friendly
      immunoassay for mycotoxin fumonisin B(1) based on using peptide-MBP fusion
      protein as substitute for coating antigen.
AB  - Here, on the basis of mimotope of small analytes, we demonstrated a new approach
      for development of sensitive and environmentally friendly immunoassay for toxic
      small analytes based on the peptide-MBP fusion protein. In this work, using
      mycotoxin fumonisin B1 (FB1) as a model hapten, phage displayed peptide
      (mimotope) that binds to the anti-FB1 antibody were selected by biopanning from a
      12-mer peptide library. The DNA coding for the sequence of peptide was cloned
      into Escherichia coli ER2738 as a fusion protein with a maltose binding protein
      (MBP). The prepared peptide-MBP fusion protein are "clonable" homogeneous and FB1
      free products and can be used as a coating antigen in the immunoassay. The half
      inhibition concentration of the quantitative immunoassay setup with fusion
      protein (F1-MBP and F15-MBP) was 2.15 +/- 0.13 ng/mL and 1.26 +/- 0.08 ng/mL,
      respectively. The fusion protein (F1-MBP) was also used to develop a qualitative
      Elispot assay with a cutoff level of 2.5 ng/mL, which was 10-fold more sensitive
      than that measured for chemically synthesized FB1-BSA conjugates based Elispot
      immunoassay. The peptide-MBP fusion protein not only can be prepared reproducibly
      as homogeneous and FB1-free products in a large-scale but also can contribute to
      the development of a highly sensitive immunoassay for analyzing FB1. Furthermore,
      the novel concept might provide potential applications to a general method for
      the immunoassay of various toxic small molecules. 

PMID- 25052469
TI  - Multivariate sequence analysis reveals additional function impacting residues in
      the SDR superfamily.
AB  - The "extended" type of short chain dehydrogenases/reductases (SDR), share a
      remarkable similarity in their tertiary structures inspite of being highly
      divergent in their functions and sequences. We have carried out principal
      component analysis (PCA) on structurally equivalent residue positions of 10 SDR
      families using information theoretic measures like Jensen-Shannon divergence and
      average shannon entropy as variables. The results classify residue positions in
      the SDR fold into six groups, one of which is characterized by low Shannon
      entropies but high Jensen-Shannon divergence against the reference family SDR1E,
      suggesting that these positions are responsible for the specific functional
      identities of individual SDR families, distinguishing them from the reference
      family SDR1E. Site directed mutagenesis of three residues from this group in the
      enzyme UDP-Galactose 4-epimerase belonging to SDR1E shows that the mutants
      promote the formation of NADH containing abortive complexes. Finally, molecular
      dynamics simulations have been used to suggest a mechanism by which the mutants
      interfere with the re-oxidation of NADH leading to the formation of abortive
      complexes.

PMID- 25052470
TI  - The effect of baseline pressure errors on an intracranial pressure-derived index:
      results of a prospective observational study.
AB  - BACKGROUND: In order to characterize the intracranial pressure-volume reserve
      capacity, the correlation coefficient (R) between the ICP wave amplitude (A) and
      the mean ICP level (P), the RAP index, has been used to improve the diagnostic
      value of ICP monitoring. Baseline pressure errors (BPEs), caused by spontaneous
      shifts or drifts in baseline pressure, cause erroneous readings of mean ICP.
      Consequently, BPEs could also affect ICP indices such as the RAP where in the
      mean ICP is incorporated. METHODS: A prospective, observational study was carried
      out on patients with aneurysmal subarachnoid hemorrhage (aSAH) undergoing ICP
      monitoring as part of their surveillance. Via the same burr hole in the scull,
      two separate ICP sensors were placed close to each other. For each consecutive 6
      sec time window, the dynamic mean ICP wave amplitude (MWA; measure of the
      amplitude of the single pressure waves) and the static mean ICP, were computed.
      The RAP index was computed as the Pearson correlation coefficient between the MWA
      and the mean ICP for 40 6-sec time windows, i.e. every subsequent 4-min period
      (method 1). We compared this approach with a method of calculating RAP using a 4
      min moving window updated every 6 seconds (method 2). RESULTS: The study included
      16 aSAH patients. We compared 43,653 4-min RAP observations of signals 1 and 2
      (method 1), and 1,727,000 6-sec RAP observations (method 2). The two methods of
      calculating RAP produced similar results. Differences in RAP >= 0.4 in at least
      7% of observations were seen in 5/16 (31%) patients. Moreover, the combination of
      a RAP of >= 0.6 in one signal and <0.6 in the other was seen in >= 13% of RAP
      observations in 4/16 (25%) patients, and in >= 8% in another 4/16 (25%) patients.
      The frequency of differences in RAP >0.2 was significantly associated with the
      frequency of BPEs (5 mmHg <= BPE <10 mmHg). CONCLUSIONS: Simultaneous monitoring
      from two separate, close-by ICP sensors reveals significant differences in RAP
      that correspond to the occurrence of BPEs. As differences in RAP are of
      magnitudes that may alter patient management, we do not advocate the use of RAP
      in the management of neurosurgical patients.

PMID- 25052471
TI  - Post- harvest consideration factors for microRNA research in cellular, tissue,
      serum and plasma samples.
AB  - MicroRNA plays important regulatory roles on the genetic network which provides
      researchers with valuable novel mechanistic directions and perspectives for
      applications in a wide variety of fields. Despite pertinent insight gained from
      messenger RNA, microRNAs possess distinct biochemical properties that emphasize
      the need for independent research to be conducted that addresses specifically
      microRNA handling. This review provides a brief summary on the various factors at
      post-sample harvesting stages with focus on microRNA from cellular, tissue,
      plasma and serum samples. It incorporates an up-to-date discussion on the
      isolation methods, quality control, profiling methods and other post-harvesting
      factors in microRNA research.

PMID- 25052472
TI  - The biofilm mode of life boosts the anti-inflammatory properties of
      Lactobacillus.
AB  - The predominant form of life for microorganisms in their natural habitats is the
      biofilm mode of growth. The adherence and colonization of probiotic bacteria are
      considered as essential factors for their immunoregulatory function in the host.
      Here, we show that Lactobacillus casei ATCC334 adheres to and colonizes the gut
      of zebrafish larvae. The abundance of pro-inflammatory cytokines and the
      recruitment of macrophages were low when inflammation was induced in probiotic
      fed animals, suggesting that these bacteria have anti-inflammatory properties. We
      treated human macrophage-differentiated monocytic THP-1 cells with supernatants
      of L. casei ATCC334 grown in either biofilm or planktonic cultures. TNF-alpha
      production was suppressed and the NF-kappaB pathway was inhibited only in the
      presence of supernatants from biofilms. We identified GroEL as the biofilm
      supernatant compound responsible, at least partially, for this anti-inflammatory
      effect. Gradual immunodepletion of GroEL demonstrated that the abundance of GroEL
      and TNF-alpha were inversely correlated. We confirmed that biofilm development in
      other Lactobacillus species affects the immune response. The biofilms
      supernatants of these species also contained large amounts of GroEL. Thus, our
      results demonstrate that the biofilm enhances the immunomodulatory effects of
      Lactobacillus sp. and that secreted GroEL is involved in this beneficial effect.

PMID- 25052473
TI  - Estrogen and its role in thyroid cancer.
AB  - Proliferative thyroid diseases are more prevalent in females than in males. Upon
      the onset of puberty, the incidence of thyroid cancer increases in females only
      and declines again after menopause. Estrogen is a potent growth factor both for
      benign and malignant thyroid cells that may explain the sex difference in the
      prevalence of thyroid nodules and thyroid cancer. It exerts its growth-promoting
      effect through a classical genomic and a non-genomic pathway, mediated via a
      membrane-bound estrogen receptor. This receptor is linked to the tyrosine kinase
      signaling pathways MAPK and PI3K. In papillary thyroid carcinomas, these pathways
      may be activated either by a chromosomal rearrangement of the tyrosine receptor
      kinase TRKA, by RET/PTC genes, or by a BRAF mutation and, in addition, in females
      they may be stimulated by high levels of estrogen. Furthermore, estrogen is
      involved in the regulation of angiogenesis and metastasis that are critical for
      the outcome of thyroid cancer. In contrast to other carcinomas, however, detailed
      knowledge on this regulation is still missing for thyroid cancer.

PMID- 25052474
TI  - Castration-induced bone loss triggers growth of disseminated prostate cancer
      cells in bone.
AB  - Up to 90% of patients with castrate-resistant prostate cancer develop bone
      metastases, and the majority of these men have received androgen deprivation
      therapy known to cause bone loss. Whether this treatment-induced change to the
      bone microenvironment affects disseminated tumour cells, potentially stimulating
      development of bone metastasis, remains to be determined. The objective of this
      study was to use an in vivo model mimicking androgen ablation to establish the
      effects of this intervention on disseminated prostate cancer cells in bone. We
      mimicked the effects of androgen deprivation on bone metastasis by castrating 12
      week-old BALB/c nude mice that had disseminated, hormone-insensitive PC3 prostate
      cancer cells present in the long bones. Castration caused increased bone
      resorption and loss of bone volume, compared with sham operation. In addition,
      castration triggered growth of disseminated PC3 cells to form bone metastasis in
      70% of animals. In contrast, only 10% of sham-operated animals had detectable
      long bone tumours. Weekly administration of 100 MUg/kg zoledronic acid (ZOL)
      prevented castration-induced tumour growth in bone and increased bone volume, but
      did not eliminate the disseminated tumour cells. ZOL had no effect on tumour
      growth in the sham-operated animals, despite causing a significant increase in
      bone volume. This is the first demonstration that, in a model of prostate cancer
      bone metastasis, mimicking androgen ablation results in growth of disseminated
      tumour cells in bone through osteoclast-mediated mechanisms. We provide the first
      biological evidence supporting the administration of ZOL to prostate cancer
      patients at the time of androgen ablation to prevent subsequent relapse in bone.

PMID- 25052475
TI  - Regression of electrocardiographic left ventricular hypertrophy or strain is
      associated with lower incidence of cardiovascular morbidity and mortality in
      hypertensive patients independent of blood pressure reduction - A LIFE review.
AB  - Cornell product criteria, Sokolow-Lyon voltage criteria and electrocardiographic
      (ECG) strain (secondary ST-T abnormalities) are markers for left ventricular
      hypertrophy (LVH) and adverse prognosis in population studies. However, the
      relationship of regression of ECG LVH and strain during antihypertensive therapy
      to cardiovascular (CV) risk was unclear before the Losartan Intervention for
      Endpoint Reduction in Hypertension (LIFE) study. We reviewed findings on ECG LVH
      regression and strain over time in 9193 hypertensive patients with ECG LVH at
      baseline enrolled in the LIFE study. The composite endpoint of CV death, nonfatal
      MI, or stroke occurred in 1096 patients during 4.8+/-0.9years follow-up. In Cox
      multivariable models adjusting for randomized treatment, known risk factors
      including in-treatment blood pressure, and for severity ECG LVH by Cornell
      product and Sokolow-Lyon voltage, baseline ECG strain was associated with a 33%
      higher risk of the LIFE composite endpoint (HR. 1.33, 95% CI [1.11-1.59]).
      Development of new ECG strain between baseline and year-1 was associated with a 2
      fold increased risk of the composite endpoint (HR. 2.05, 95% CI [1.51-2.78]),
      whereas the risk associated with regression or persistence of ECG strain was
      attenuated and no longer statistically significant (both p>0.05). After
      controlling for treatment with losartan or atenolol, for baseline Framingham risk
      score, Cornell product, and Sokolow-Lyon voltage, and for baseline and in
      treatment systolic and diastolic blood pressure, 1 standard deviation (SD) lower
      in-treatment Cornell product was associated with a 14.5% decrease in the
      composite endpoint (HR. 0.86, 95% CI [0.82-0.90]). In a parallel analysis, 1 SD
      lower in-treatment Sokolow-Lyon voltage was associated with a 16.6% decrease in
      the composite endpoint (HR. 0.83, 95% CI [0.78-0.88]). The LIFE study shows that
      evaluation of both baseline and in-study ECG LVH defined by Cornell product
      criteria, Sokolow-Lyon voltage criteria or ECG strain improves prediction of CV
      events and that regression of ECG LVH during antihypertensive treatment is
      associated with better outcome, independent of blood pressure reduction. 

PMID- 25052476
TI  - Use of the distress thermometer to evaluate symptoms, outcome and satisfaction in
      a specialist psycho-oncology service.
AB  - OBJECTIVE: The National Institute for Health and Care Excellence recommends the
      use of structured tools to improve holistic care for patients with cancer. The
      Distress Thermometer and Problem Checklist (DT) is commonly used for screening in
      physical health settings. However, it has not been integrated into the clinical
      pathway within specialist psycho-oncology services. We used the DT to examine the
      broad clinical effectiveness of psycho-oncology intervention and to ascertain
      factors from the DT linked to an improved outcome. We also evaluated patients'
      satisfaction with their care. METHOD: We asked 111 adult outpatients referred to
      York Psycho-Oncology Service to complete the DT at their first appointment.
      Individuals offered a period of psycho-oncology care re-rated their emotional
      distress, problems and service satisfaction on the DT at discharge. RESULTS:
      Median distress scores decreased significantly (from 6 to 4, Wilcoxon's z = 
      4.83, P < .001) indicating a large clinical effect size (Cohen's d = 1.22).
      Frequency of emotional problems (anxiety, depression and anger) fell
      significantly by 15-24% despite no significant change in patients' physical
      health or practical problems. Number of emotional problems was the best predictor
      of distress at discharge (beta = 0.468, P = .002). Satisfaction was high and
      correlated with lower distress scores (r = -0.42, P = .005) and fewer emotional
      problems (r = -0.31, P = .04) at discharge but not with number of appointments
      attended. Qualitative thematic analysis showed patients particularly value
      supportive listening and advice on coping strategies from professionals
      independent of their physical care. CONCLUSION: The DT is an acceptable and
      useful tool for enhancing the delivery of structured psycho-oncology care. It may
      also provide evidence to support the effectiveness of specialist psycho-oncology
      interventions.

PMID- 25052477
TI  - Protease inhibitor reduces airway response and underlying inflammation in
      cockroach allergen-induced murine model.
AB  - Protease(s) enhances airway inflammation and allergic cascade. In the present
      study, effect of a serine protease inhibitor was evaluated in mouse model of
      airway disease. Mice were sensitized with cockroach extract (CE) or Per a 10 and
      treated with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) 1 h
      before or after challenge to measure airway response. Mice were euthanized to
      collect bronchoalveolar lavage fluid (BALF), blood, and lung to evaluate
      inflammation. AEBSF treatment significantly reduced the AHR in allergen
      challenged mice in dose-dependent manner (p<= 0.01). IgE (p<=0.05) and Th2
      cytokines (p<=0.05) were significantly reduced in treated mice. AEBSF treatment
      lowered total cell (p<=0.05), eosinophil (p<=0.05), and neutrophil (p<=0.05) in
      BALF and lung tissue. Oxidative stress parameters were impaired on treatment in
      allergen-challenged mice (p<=0.05). AEBSF had therapeutic effect in allergen
      induced airway resistance and underling inflammation and had potential for
      combination or as add-on therapy for respiratory diseases.

PMID- 25052478
TI  - The effect of synthetic salidroside on cytokines and airway inflammation of
      asthma induced by diisocyanate (TDI) in mice by regulating GATA3/T-bet.
AB  - This study was conducted to explore the anti-asthma effects of synthetic
      salidroside on cytokines and airway inflammation of asthma induced by
      diisocyanate (TDI) in mice. The experiment was carried out 60 female BALB/C mice
      which were randomly assigned to six experimental groups: control, vehicle, model,
      dexamethasone (2 mg/kg), and salidroside (24 and 48 mg/kg). After the experiment,
      histological studies were evaluated by the hematoxylin and eosin staining, the
      bronchoalveolar lavage fluid (BALF) and blood were collected from the animals,
      and the composition of the induced inflammatory cells, and the concentrations of
      certain cytokines (IL-4, INF-gamma) were evaluated. GATA3 and T-bet mRNAs were
      evaluated by QPCR. Our study demonstrated that salidroside inhibited TDI-induced
      increases in eosinophil count; IL-4 and INF-gamma were recovered. Histological
      studies demonstrated that salidroside substantially inhibited TDI-induced
      eosinophilia in lung tissue. Salidroside can improve T-bet mRNA and reduce GATA3
      mRNA in lung. These findings suggest that salidroside may effectively ameliorate
      the progression of asthma and could be used as a therapy for patients with
      allergic asthma by regulating GATA3/T-bet balance. 

PMID- 25052479
TI  - Monitoring reversal of MET-mediated resistance to EGFR tyrosine kinase inhibitors
      in non-small cell lung cancer using 3'-deoxy-3'-[18F]-fluorothymidine positron
      emission tomography.
AB  - PURPOSE: MET amplification is one of the mechanisms underlying acquired
      resistance to EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer
      (NSCLC). Here, we tested whether 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT)
      positron emission tomography/computerized tomography (PET/CT) can detect MET
      mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in
      NSCLC. EXPERIMENTAL DESIGN: H1993 and H820 NSCLC cells with high and low levels
      of MET amplification, respectively, and HCC827-expressing MET, but without gene
      amplification, were tested for the effects of MET inhibitors on the EGFR pathway
      and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and
      without MET amplification were subjected to [(18)F]FLT PET/CT before and after
      treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days).
      RESULTS: H1993 cells showed high responsiveness to MET inhibitors and were
      resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to
      erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing
      MET amplification showed a mean reduction in [(18)F]FLT uptake of 28% and 41%
      after low- and high-dose treatment with crizotinib for 3 days, whereas no
      posttherapy changes of [(18)F]FLT uptake were observed in HCC827 tumors lacking
      MET amplification. Furthermore, a persistently high [(18)F]FLT uptake was
      observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors
      showed up to 39% reduction of [(18)F]FLT uptake following erlotinib treatment.
      Imaging findings were confirmed by Ki67 immunostaining of tumor sections.
      CONCLUSIONS: [(18)F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs
      and its reversal by MET inhibitors in NSCLC.

PMID- 25052481
TI  - TYROBP in Alzheimer's disease.
AB  - Recently, studies have provided convincing data that TYRO protein tyrosine kinase
      binding protein (TYROBP), a key regulator in immune systems, is significantly
      upregulated in the brain of patients with Alzheimer's disease (AD). TYROBP acts
      as a signaling adaptor protein for numerous cell surface receptors, playing
      important roles in signal transduction in dendritic cells, osteoclasts,
      macrophages, and microglia. Although several TYROBP-related cell surface
      receptors including triggering receptor expressed on myeloid 2 (TREM2), signal
      regulatory protein beta1 (SIRPbeta1), and complement receptor 3 (CR3) were found
      to participate in the pathogenesis of AD, the role of TYROBP in AD still remains
      elusive. Emerging piece of evidence has demonstrated that TYROBP could enhance
      phagocytic activity of microglia, which is responsible for the clearance of
      amyloid-beta (Abeta) peptides and apoptotic neurons. TYROBP also participates in
      suppression of inflammatory responses by repression of microglia-mediated
      cytokine production and secretion. In this article, we introduce the structure,
      localization, and function of TYROBP. Meanwhile, we review recent articles
      concerning the association of TYROBP and its related receptors with AD
      pathogenesis and speculate the possible roles of TYROBP in this disease. Based on
      the potential protective actions of TYROBP in AD pathogenesis, targeting TYROBP
      might provide new opportunities for AD treatment.

PMID- 25052480
TI  - Axonal transport defects in Alzheimer's disease.
AB  - A large body of evidences indicates that axonal transport (AT) defects play an
      important role in the pathogenesis of Alzheimer' disease (AD). AT, a critical
      cellular process for the maintenance and function of a neuron, requires
      components of the cytoskeletons as "tracks", motor proteins and ATP as "driving
      force", adaptor proteins to ensure the specific connection of the transported
      cargoes and motor proteins as well as active regulation. In AD pathology, AD
      linked pathologic factors respectively perturb the four basic components of AT
      through different signaling pathways to cause AT defects. Mitochondrial
      transport, which is different from other transport cargoes, is also impaired via
      special pathways in AD. In this paper, we review the inhibitory effects of those
      factors on AT and their possible pathways, indicating these factors act in
      overlapping, synergistic, and circulating ways. Given the contributions of AT
      defects to AD, recent therapeutic studies focus on microtubule-stabilizing (MT
      stabilizing) agents and alteration in phosphotransferase activities, and we
      propose more therapeutic strategies targeting AT defects. 

PMID- 25052482
TI  - Crystallization and preliminary X-ray diffraction analysis of eukaryotic alpha2 
      macroglobulin family members modified by methylamine, proteases and glycosidases.
AB  - alpha2 -Macroglobulin (alpha2 M) has many functions in vertebrate physiology. To
      understand the basis of such functions, high-resolution structural models of its
      conformations and complexes with interacting partners are required. In an attempt
      to grow crystals that diffract to high or medium resolution, we isolated native
      human alpha2 M (halpha2 M) and its counterpart from chicken egg white (ovostatin)
      from natural sources. We developed specific purification protocols, and modified
      the purified proteins either by deglycosylation or by conversion to their induced
      forms. Native proteins yielded macroscopically disordered crystals or crystals
      only diffracting to very low resolution (>20 A), respectively. Optimization of
      native halpha2 M crystals by varying chemical conditions was unsuccessful, while
      dehydration of native ovostatin crystals improved diffraction only slightly (10
      A). Moreover, treatment with several glycosidases hindered crystallization. Both
      proteins formed spherulites that were unsuitable for X-ray analysis, owing to a
      reduction of protein stability or an increase in sample heterogeneity. In
      contrast, transforming the native proteins to their induced forms by reaction
      either with methylamine or with peptidases (thermolysin and chymotrypsin)
      rendered well-shaped crystals routinely diffracting below 7 A in a reproducible
      manner.

PMID- 25052483
TI  - New 2-(1'H-indole-3'-carbonyl)-thiazoles derived from the thermophilic bacterium
      Thermosporothrix hazakensis SK20-1(T).

PMID- 25052484
TI  - Mechanisms of beta-lactam killing and resistance in the context of Mycobacterium
      tuberculosis.
AB  - beta-Lactams are one of the most useful classes of antibiotics against many
      common bacterial pathogens. One exception is Mycobacterium tuberculosis. However,
      with increasing incidence of multidrug-resistant tuberculosis and a need for new
      agents to treat it, the use of beta-lactams, specifically the combination of
      carbapenem and clavulanate, is now being revisited. With this attention, comes
      the need to better understand both the mechanisms of action of beta-lactams
      against M. tuberculosis as well as possible mechanisms of resistance, within the
      context of what is known about the beta-lactam action in other bacteria. M.
      tuberculosis has two major mechanisms of intrinsic resistance: a highly active
      beta-lactamase and a poorly permeable outer membrane. Within the cell wall, beta
      lactams bind several enzymes with differing peptidoglycan-synthetic and -lytic
      functions. The inhibition of these enzymes may lead to cell death through several
      mechanisms, involving disruption of the balance of synthetic and lethal
      activities. Currently, all known means of resistance to the beta-lactams rely on
      diminishing the proportion of peptidoglycan-synthetic proteins bound and
      inhibited by beta-lactams, through either exclusion or destruction of the
      antibiotic, or through replacement or supplementation of target enzymes. In this
      review, we discuss possible mechanisms for beta-lactam activity in M.
      tuberculosis and the means by which it may acquire resistance, within the context
      of what is known in other bacterial species. 

PMID- 25052485
TI  - Prevalence of gyrA and B gene mutations in fluoroquinolone-resistant and 
      sensitive clinical isolates of Mycobacterium tuberculosis and their relationship
      with MIC of ofloxacin.
AB  - The study was done to know the prevalent mutations of gyrA and gyrB genes, and
      their significance with drug resistance in clinical isolates of Mycobacterium
      tuberculosis. A total of 100 ofloxacin- (OFX) resistant and 100 OFX-sensitive
      isolates of M. tuberculosis were consecutively selected from routine Tuberculosis
      laboratory. Drug resistance pattern of these isolates was recorded. MIC of OFX
      was tested in all these isolates by absolute concentration method. Quinolone
      resistance determining region (QRDR) of gyrA and gyrB genes of 320 and 428 bp,
      respectively, were amplified and sequenced. Sequencing data were analyzed by
      BLAST on NCBI with reference strain H37Rv. Of 100 OFX-sensitive isolates, 30 were
      pansusceptible, 28 were monoresistant, 10 were polyresistant and 32 were
      multidrug resistant (MDR). Among 100 OFX-resistant isolates, 19 were OFX
      monoresistant, 16 were polyresistant and 65 were MDR. Mutations in gyrA and gyrB
      genes were observed in 79% and 5% of OFX-resistant isolates, respectively. Most
      prevalent mutation was found at codon 94 in QRDR of gyrA gene. Double mutations
      found in gyrA gene and in both gyrA and gyrB genes signifies higher levels of OFX
      resistance. In one isolate, a substitution at codon 592 (Pro592Ser) was found as
      a novel mutation outside the QRDR of gyrB gene. Our findings support previous
      studies that the OFX resistance to M. tuberculosis is associated with mutations
      in the QRDR of gyrA gene; however, the level of OFX resistance may not be
      predicted based on the mutation patterns in the gyrA gene.

PMID- 25052486
TI  - Self-regulatory failure and the perpetration of adolescent dating violence:
      Examining an alcohol use by gene explanation.
AB  - Studies report that alcohol use is related to partner violence, but for many,
      alcohol use does not culminate in violence against partners. Guided by a self
      regulatory failure framework, we predicted that alcohol use would be more
      strongly associated with dating violence perpetration among adolescents with
      genotypes linked to impulsivity and emotional reactivity. The hypothesis was
      tested using random coefficient modeling of data from a multi-wave longitudinal
      study spanning grades 8-12 (ages 13-18) (n = 1,475). Analyses adjusted for
      multiple testing and race, and the potential for gene by environment correlation
      was examined. As predicted, alcohol use was more strongly associated with dating
      violence among adolescents who had a high rather than a low multilocus genetic
      profile composed of five genetic markers that influence dopamine signaling.
      Alcohol use was more strongly related to dating violence among boys with long
      rather than short 5-HTTLPR alleles, the opposite of the prediction. MAOA-uVNTR
      did not interact with alcohol, but it had a main effect on dating violence by
      boys in later grades in the expected direction: boys with more low activity
      alleles perpetrated more dating violence. Exploratory analyses found variation in
      findings by race. Our findings demonstrate the importance of incorporating genes
      into etiological studies of adolescent dating violence, which to date has not
      been done. Aggr. Behav. Aggr. Behav. 42:189-203, 2015. (c) 2014 Wiley
      Periodicals, Inc. 

PMID- 25052488
TI  - Corrigendum.

PMID- 25052487
TI  - Endoscopic transpterygoid approach and skull base repair after sphenoid
      meningoencephalocele resection. Our experience.
AB  - INTRODUCTION AND OBJECTIVES: Cerebrospinal fluid leaks associated to
      meningoencephaloceles of the sphenoid lateral recess are rare entities. A
      congenital bony defect at this level results in the persistence of Sternberg's
      canal, or a lateral craniopharyngeal canal, which is supposed to be the origin of
      these lesions. Our objective was to show that the endoscopic transpterygoid
      approach is an effective technique for their treatment. METHODS: We present a
      series of 5 cases of meningoencephaloceles of the sphenoid lateral recess treated
      with endoscopic sinus surgery (4 women and one man; mean age=59, range 37-72
      years). Cerebrospinal fluid rhinorrhoea was present in all of them and they all
      underwent a transpterygoid approach with reconstruction of the skull base. We
      describe the surgical technique and review the literature. RESULTS: No
      complications were observed during surgery or the postoperative period. After a
      mean follow-up of 81 months, only one recurrence was seen. CONCLUSIONS: The
      transpterygoid approach has proven to be effective for the treatment of
      meningoencephaloceles of the sphenoid lateral recess. Providing wide access to
      identify the defect, followed by meningoencephalocele ablation, is the key for
      successful surgery.

PMID- 25052489
TI  - Prolonged acute kidney injury exacerbates lung inflammation at 7 days post-acute
      kidney injury.
AB  - Patients with acute kidney injury (AKI) have increased mortality; data suggest
      that the duration, not just severity, of AKI predicts increased mortality. Animal
      models suggest that AKI is a multisystem disease that deleteriously affects the
      lungs, heart, brain, intestine, and liver; notably, these effects have only been
      examined within 48 h, and longer term effects are unknown. In this study, we
      examined the longer term systemic effects of AKI, with a focus on lung injury.
      Mice were studied 7 days after an episode of ischemic AKI (22 min of renal
      pedicle clamping and then reperfusion) and numerous derangements were present
      including (1) lung inflammation; (2) increased serum proinflammatory cytokines;
      (3) liver injury; and (4) increased muscle catabolism. Since fluid overload may
      cause respiratory complications post-AKI and fluid management is a critical
      component of post-AKI care, we investigated various fluid administration
      strategies in the development of lung inflammation post-AKI. Four different fluid
      strategies were tested - 100, 500, 1000, or 2000 MUL of saline administered
      subcutaneously daily for 7 days. Interestingly, at 7 days post-AKI, the 1000 and
      2000 MUL fluid groups had less severe AKI and less severe lung inflammation
      versus the 100 and 500 MUL groups. In summary, our data demonstrate that
      appropriate fluid management after an episode of ischemic AKI led to both (1)
      faster recovery of kidney function and (2) significantly reduced lung
      inflammation, consistent with the notion that interventions to shorten AKI
      duration have the potential to reduce complications and improve patient outcomes.

PMID- 25052490
TI  - Quantitative immunofluorescence microscopy of subcellular GLUT4 distribution in
      human skeletal muscle: effects of endurance and sprint interval training.
AB  - Increases in insulin-mediated glucose uptake following endurance training (ET)
      and sprint interval training (SIT) have in part been attributed to concomitant
      increases in glucose transporter 4 (GLUT4) protein content in skeletal muscle.
      This study used an immunofluorescence microscopy method to investigate changes in
      subcellular GLUT4 distribution and content following ET and SIT. Percutaneous
      muscle biopsy samples were taken from the m. vastus lateralis of 16 sedentary
      males in the overnight fasted state before and after 6 weeks of ET and SIT. An
      antibody was fully validated and used to show large (> 1 MUm) and smaller (<1
      MUm) GLUT4-containing clusters. The large clusters likely represent trans-Golgi
      network stores and the smaller clusters endosomal stores and GLUT4 storage
      vesicles (GSVs). Density of GLUT4 clusters was higher at the fibre periphery
      especially in perinuclear regions. A less dense punctate distribution was seen in
      the rest of the muscle fibre. Total GLUT4 fluorescence intensity increased in
      type I and type II fibres following both ET and SIT. Large GLUT4 clusters
      increased in number and size in both type I and type II fibres, while the smaller
      clusters increased in size. The greatest increases in GLUT4 fluorescence
      intensity occurred within the 1 MUm layer immediately adjacent to the PM. The
      increase in peripheral localisation and protein content of GLUT4 following ET and
      SIT is likely to contribute to the improvements in glucose homeostasis observed
      after both training modes. 

PMID- 25052491
TI  - Lack of megalin expression in adult human terminal ileum suggests megalin
      independent cubilin/amnionless activity during vitamin B12 absorption.
AB  - Cubilin plays an essential role in terminal ileum and renal proximal tubules
      during absorption of vitamin B12 and ligands from the glomerular ultrafiltrate.
      Cubilin is coexpressed with amnionless, and cubilin and amnionless are mutually
      dependent on each other for correct processing to the plasma membrane upon
      synthesis. Patients with defects in either protein suffer from vitamin B12
      malabsorption and in some cases proteinuria. Cubilin lacks a transmembrane region
      and signals for endocytosis and is dependent on a transmembrane coreceptor during
      internalization. Amnionless has been shown to be able to mediate internalization
      of cubilin in a cell-based model system. Cubilin has additionally been suggested
      to function together with megalin, and a recent study of megalin-deficient
      patients indicates that uptake of cubilin ligands in the kidney is critically
      dependent on megalin. To further investigate the potential role of amnionless and
      megalin in relation to cubilin function in terminal ileum and vitamin B12 uptake,
      we initiated a study of CUBN/cubilin, AMN/amnionless, and LRP2/megalin expression
      in adult human terminal ileum. Our study is the first to reveal the expression
      pattern of cubilin, amnionless, and megalin in adult human terminal ileum, where
      cubilin and amnionless localize to the epithelial cells. Surprisingly, we did not
      detect any megalin protein in adult terminal ileum and consistently, only
      extremely low amounts of LRP2 mRNA. Our data therefore advocate that cubilin and
      amnionless act independently of megalin in adult terminal ileum and that the
      cubilin-megalin interdependency accordingly should be considered as tissue and
      ligand specific. 

PMID- 25052492
TI  - Automated quantification of renal fibrosis with Sirius Red and polarization
      contrast microscopy.
AB  - Interstitial fibrosis is commonly measured by histology. The Masson trichrome
      stain is widely used, with semiquantitative scores subjectively assigned by
      trained operators. We have developed an objective technique combining Sirius Red
      staining, polarization contrast microscopy, and automated analysis. Repeated
      analysis of the same sections by the same operator (r = 0.99) or by different
      operators (r = 0.98) was highly consistent for Sirius Red, while Masson trichrome
      performed less consistently (r = 0.61 and 0.72, respectively). These techniques
      performed equally well when comparing sections from the left and right kidneys of
      mice. Poor correlation between Sirius Red and Masson trichrome may reflect
      different specificities, as enhanced birefringence with Sirius Red staining is
      specific for collagen type I and III fibrils. Combining whole-section imaging and
      automated image analysis with Sirius Red/polarization contrast is a rapid,
      reproducible, and precise technique that is complementary to Masson trichrome. It
      also prevents biased selection of fields as fibrosis is measured on the entire
      kidney section. This new tool shall enhance our search for novel therapeutics and
      noninvasive biomarkers for fibrosis. 

PMID- 25052493
TI  - Dietary nitrate reduces skeletal muscle oxygenation response to physical
      exercise: a quantitative muscle functional MRI study.
AB  - Dietary inorganic nitrate supplementation (probably via conversion to nitrite)
      increases skeletal muscle metabolic efficiency. In addition, it may also cause
      hypoxia-dependent vasodilation and this has the potential to augment oxygen
      delivery to exercising skeletal muscle. However, direct evidence for the latter
      with spatial localization to exercising muscle groups does not exist. We employed
      quantitative functional MRI (fMRI) to characterize skeletal muscle oxygen
      utilization and replenishment by assessment of tissue oxygenation maximal change
      and recovery change, respectively. Eleven healthy subjects were enrolled, of whom
      9 (age 33.3 +/- 4.4 years, five males) completed the study. Each subject took
      part in three MRI visits, with dietary nitrate (7cl concentrated beetroot juice)
      consumed before the third visit. During each visit fMRIs were conducted
      concurrently with plantar flexion exercise at workloads of 15% and 25% maximum
      voluntary contraction (MVC). No significant changes were found between visits 1
      and 2 in the fMRI measures. A decrease in maximal change was found at 15% MVC in
      soleus between visits 2 and 3 (5.12 +/- 2.36 to 2.55 +/- 1.42, P = 0.004) and
      between visits 1 and 3 (4.43 +/- 2.12 to 2.55 +/- 1.42, P = 0.043), but not at
      25% MVC or within gastrocnemius. There was no difference in recovery change
      between visits. We found that dietary nitrate supplementation reduces tissue
      oxygenation alterations during physical exercise in skeletal muscle. This effect
      is more prominent in muscles with predominantly type 1 fibers and at lower
      workloads. This indicates that in healthy subjects dietary nitrate predominantly
      affects skeletal muscle energy efficiency with no change in oxygen delivery. 

PMID- 25052495
TI  - Baltimore City's landmark alcohol and tobacco billboard ban: an implementation
      case study.

PMID- 25052494
TI  - Ascorbic acid does not enhance hypoxia-induced vasodilation in healthy older men.
AB  - In response to hypoxia, a net vasodilation occurs in the limb vasculature in
      young healthy humans and this is referred to as "hypoxia-induced vasodilation".
      We performed two separate experiments to determine (1) if hypoxia-induced forearm
      vasodilation is impaired in older men (n = 8) compared to young men (n = 7) and
      (2) if acute systemic infusion of ascorbic acid would enhance hypoxia-induced
      vasodilation in older men (n = 8). Heart rate, mean arterial pressure, oxygen
      saturation, minute ventilation, forearm vascular conductance (FVC, Doppler
      ultrasound), and cutaneous vascular conductance (CVC, laser Doppler flowmetry)
      were recorded continuously while subjects breathed 10% oxygen for 5 min. Changes
      from baseline were compared between groups and between treatments. The older
      adults had a significantly attenuated increase in FBF (13 +/- 4 vs. 30 +/- 7%)
      and FVC (16 +/- 4 vs. 30 +/- 7%) in response to 5 min of hypoxia. However, skin
      blood flow responses were comparable between groups (young: 35 +/- 9, older: 30
      +/- 6%). In Experiment 2, FVC responses to 5 min of breathing 10% oxygen were not
      significantly different following saline (3 +/- 10%) and ascorbic acid (8 +/-
      10%) in the older men. Ascorbic acid also had no physiological effects in the
      young men. These findings advance our basic understanding of how aging influences
      vascular responses to hypoxia and suggest that, in healthy humans, hypoxia
      induced vasodilation is not restrained by reactive oxygen species. 

PMID- 25052496
TI  - Rapid assessment of road safety policy change: relaxation of the national speed
      enforcement law in Russia leads to large increases in the prevalence of speeding.
AB  - Reducing vehicle speed is among the most effective road safety strategies. We
      assess how a new policy in Russia that eliminates fines for driving up to 20 km/h
      above the speed limit has affected the prevalence of speeding. We measured speeds
      periodically in 13 districts of two Russian regions during 2011-2013 and analysed
      the effect of the policy using difference-in-differences to control for
      seasonality. We find that the prevalence of speeding was declining steadily but
      half of the gains since mid-2011 were lost immediately after the new policy.
      Overall speeding increased significantly by 13 percentage points (pp, 95% CI 4 to
      19). Speeding more than 10 km/h above the limit increased significantly by 10 pp
      (95% CI 2 to 12), and extreme speeding increased but not significantly (1.7 pp,
      95% CI -1.1 to 4.5). Road traffic injuries will likely increase in Russia unless
      speeding fines are reinstated.

PMID- 25052497
TI  - Primary neuroendocrine carcinoma of the breast: radiologic and pathologic
      correlation.
AB  - Primary neuroendocrine carcinoma of the breast (PNCB) is a rare type of breast
      cancer. There have been few reports on PNCB and radiologic-pathologic correlation
      in PNCB has not been described thoroughly. We present a rare case of
      pathologically confirmed poorly differentiated PNCB removed via lumpectomy. Image
      findings on mammography, ultrasonography, computed tomography, magnetic resonance
      image, and positron emission tomography-computed tomography are also presented. 

PMID- 25052498
TI  - Trends in medical oncology outreach clinics in rural areas.
AB  - PURPOSE: To examine the long-term trends in medical oncology outreach in Iowa, a
      state with a high proportion of rural residents, and to assess the involvement of
      the 2011 Iowa oncology workforce in visiting consultant clinics using a unique
      data source. METHODS: Outreach locations and clinic frequencies are tracked
      annually in the Visiting Medical Consultant Database (Carver College of Medicine)
      along with the physicians' primary practice locations. Growth in the number of
      cities served and number of clinic days from 1989 to 2011 was analyzed using
      joinpoint analysis. Data from 2011 were used to estimate the trip length for
      participating oncologists. RESULTS: The number of rural cities served by medical
      oncology outreach increased significantly between 1989 and 1996. Clinic days grew
      significantly in two periods: 1989 to 1998 and 2003 to 2005. In 2011, more than
      2,100 clinic days were provided in 66 sites (95% of clinic days in rural areas).
      Almost half of all Iowa-based oncologists regularly participate in outreach.
      Oncologists staffing visiting consultant clinics in Iowa drive an estimated
      21,000 miles per month. CONCLUSIONS: For more than 20 years, visiting medical
      oncologists have brought cancer care to rural patients in Iowa. Access to cancer
      care in rural Iowa (ie, clinic days) increased significantly in the post-Medicare
      Modernization Act period (after 2005). High participation rates and travel
      burdens may influence oncologist training and retention strategies. Because the
      Affordable Care Act seeks to expand access for vulnerable populations (eg, rural
      elderly), it is critical to better understand the existing system of rural cancer
      care delivery.

PMID- 25052500
TI  - Drivers of change in cancer care.

PMID- 25052499
TI  - Oncologists' response to new data regarding the use of epidermal growth factor
      receptor inhibitors in colorectal cancer.
AB  - PURPOSE: Although initially approved for metastatic colorectal cancer (mCRC)
      tumors with epidermal growth factor receptor (EGFR) overexpression, the use of
      anti-EGFR antibodies is now restricted to wild-type KRAS tumors. Little is known
      about prescribers' response to new clinical data, practice guidelines, and US
      Food and Drug Administration (FDA) label change with regard to the use of anti
      EGFR antibodies in clinical practice. METHODS: Commercially insured patients with
      mCRC who received second-line therapy between 2004 and 2010 were identified by
      dusing the LifeLink Health Plan Claims Database. We calculated the fraction of
      patients receiving anti-EGFR antibody in 2-month intervals. chi(2) tests were
      used to compare treatment rates at four time points: time 1: June 2008, ASCO
      presentation of clinical data; time 2: February 2009, ASCO guidelines
      publication; time 3: August 2009, FDA label change; time 4: April 2010 to 8
      months after FDA label change. RESULTS: Five thousand eighty-nine patients
      received second-line therapy; of these, 2,599 patients received an anti-EGFR
      antibody. Median age was 60 years (range, 20 to 97), with 57% male sex. The
      majority of patients (59.4%) received an anti-EGFR antibody at time 1, with
      significant decrease at each of the subsequent time points (time 2: 46.2% [P =
      .019]; time 3: 35.2% [P < .001]; Time 4: 16.2% [P < .001]). Multivariable
      logistic regression did not show any affect of age, sex, comorbidities, or region
      of the country on this pattern. CONCLUSIONS: The use of anti-EGFR antibodies for
      mCRC decreased after the presentation of clinical trial data, ASCO guidelines
      publication, and FDA label change. These data suggest that oncologists respond
      rapidly to new evidence and professional guidelines, and readily incorporate
      predictive biomarkers into clinical practice.

PMID- 25052501
TI  - Diversity by race, Hispanic ethnicity, and sex of the United States medical
      oncology physician workforce over the past quarter century.
AB  - PURPOSE: To assess the medical oncology (MO) physician workforce diversity by
      race, Hispanic ethnicity, and sex, with attention to trainees. METHODS: Public
      registries were used to assess 2010 differences among MO practicing physicians,
      academic faculty, and fellows; internal medicine (IM) residents; and the US
      population, using binomial tests with P < .001 significance adjusting for
      multiple comparisons. Significant changes in fellow representation from 1986 to
      2011 were assessed. RESULTS: Female representation as MO fellows (45.0%) was
      significantly increased compared with faculty (22.4%) and practicing physicians
      (27.4%); was no different than IM residents (44.7%, P = .853); and increased
      significantly, by 1.0% per year. Women were significantly underrepresented as
      practicing physicians, faculty, and fellows compared with the US population
      (50.8%). Traditionally underrepresented minorities in medicine (URM) were
      significantly underrepresented as practicing physicians (7.8%), faculty (5.7%),
      and fellows (10.9%), versus US population (30.0%). Hispanic MO fellows (7.5%)
      were increased compared with faculty (3.9%) and practicing physicians (4.1%);
      Black fellows (3.1%) were no different than faculty (1.8%, P = .0283) or
      practicing physicians (3.5%, P = .443). When comparing MO fellows versus IM
      residents, there were no differences for American Indians/Alaska Natives/Native
      Hawaiians/Pacific Islanders (0.3%, 0.6%, respectively, P = .137) and Hispanics
      (7.5%, 8.7%, P = .139), unlike Blacks (3.1%, 5.6%, P < .001). There has been no
      significant change in URM representation, with negligible changes every 5 years
      for American Indians/Alaska Natives/Native Hawaiians/Pacific Islanders (-0.1%),
      Blacks (-0.3%), and Hispanics (0.3%). CONCLUSIONS: Female fellow representation
      increased 1% per year over the quarter century indicating historical gains,
      whereas URM diversity remains unchanged. For Blacks alone, representation as MO
      fellows is decreased compared with IM residents, suggesting greater disparity in
      MO training.

PMID- 25052502
TI  - Effect of different design preparations on the flexural and fracture strength of
      fiber-reinforced composite fixed partial dentures: an in vitro study.
AB  - PURPOSE: To determine and compare the flexural and fracture strength of three
      unit fiber-reinforced composite (FRC) fixed partial dentures (FPDs) using three
      abutment design preparations. MATERIAL AND METHODS: The flexural and fracture
      strength of three-unit FRC FPDs were evaluated using three design preparations of
      the abutments (conventional full crown [group A], box-shaped [group B], and tub
      shaped [group C]). Thirty three-unit FRC FPDs were fabricated (10 specimens per
      group) for the replacement of missing mandibular first molars and were adhesively
      luted to extracted human teeth. The flexural and fracture strength were
      determined using a universal testing machine with a steel loading pin of 20 mm
      diameter with a 3-mm-diameter hardened circular tip. Each specimen was evaluated
      under SEM to determine mode of failure. RESULTS: Mean fracture strength for group
      A was 820.00 +/- 56.51 N, group B was 536.94 +/- 65.62 N, and group C was 501.24
      +/- 66.71 N. The highest mean flexural strength was found in group A (68.33 +/-
      4.71 MPa), followed by group B (44.74 +/- 5.46 MPa) and lowest in group C (41.77
      +/- 5.56 MPa). The SEM evaluation showed partial or complete debonding of
      veneering composite from fiber framework, leaving intact fiber frameworks in all
      the specimens. CONCLUSION: Full-coverage design had significantly higher flexural
      and fracture strengths than box and tub-shaped designs. Since both values were
      noted to be in the order of masticatory stresses, the full coverage design is a
      good alternative for the replacement of missing molar teeth; however, the
      framework veneering composite interface was the weakest phase of FRC FPDs, thus
      indicating that further improvement in veneering composite or fiber framework is
      needed to improve the compatibility of veneering composite with that of fiber
      framework for long-term clinical implications.

PMID- 25052503
TI  - The role of interleukin-17 in immune-mediated inflammatory myopathies and
      possible therapeutic implications.
AB  - The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune
      muscle disorders with distinct clinical and pathological features and underlying
      immunopathogenic mechanisms. Traditionally, CD4(+) Th1 cells or CD8(+) cytotoxic
      effector T cells and type I/II interferons have been primarily implicated in the
      pathogenesis of the inflammatory myopathies. The presence of IL-17A producing
      cells in the inflamed muscle tissue of myositis patients and the results of in
      vitro studies suggest that IL-17A and the Th17 pathway may also have a key role
      in these diseases. The contribution of IL-17A to other chronic inflammatory and
      autoimmune diseases has been well established and clinical trials of IL-17A
      inhibitors are now at an advanced stage. However the precise role of IL-17A in
      the various forms of myositis and the potential for therapeutic targeting is
      currently unknown and warrants further investigation. 

PMID- 25052504
TI  - A four-component organogel based on orthogonal chemical interactions.
AB  - A thermoresponsive organogel was obtained by orthogonal assembly of four
      compounds using dynamic covalent boronate ester and imine bonds, as well as
      dative boron-nitrogen bonds. It is shown that the gel state can be disrupted or
      reinforced by chemicals which undergo exchange reactions with the gel components.

PMID- 25052505
TI  - A retrospective analysis of a functional restoration service for patients with
      persistent low back pain.

PMID- 25052506
TI  - Accurate inference of local phased ancestry of modern admixed populations.
AB  - Population stratification is a growing concern in genetic-association studies.
      Averaged ancestry at the genome level (global ancestry) is insufficient for
      detecting the population substructures and correcting population stratifications
      in association studies. Local and phase stratification are needed for human
      genetic studies, but current technologies cannot be applied on the entire genome
      data due to various technical caveats. Here we developed a novel approach (aMAP,
      ancestry of Modern Admixed Populations) for inferring local phased ancestry. It
      took about 3 seconds on a desktop computer to finish a local ancestry analysis
      for each human genome with 1.4-million SNPs. This method also exhibits the
      scalability to larger datasets with respect to the number of SNPs, the number of
      samples, and the size of reference panels. It can detect the lack of the proxy of
      reference panels. The accuracy was 99.4%. The aMAP software has a capacity for
      analyzing 6-way admixed individuals. As the biomedical community continues to
      expand its efforts to increase the representation of diverse populations, and as
      the number of large whole-genome sequence datasets continues to grow rapidly,
      there is an increasing demand on rapid and accurate local ancestry analysis in
      genetics, pharmacogenomics, population genetics, and clinical diagnosis. 

PMID- 25052507
TI  - A physiologically based pharmacokinetic model for clobazam and stiripentol in
      adults and children.
AB  - PURPOSE: To develop a physiologically based pharmacokinetic model in adults and
      children for clobazam, its active metabolite norclobazam and stiripentol and to
      account for significant clinical interaction that has been reported when clobazam
      and stiripentol are co-administered. METHODS: A PBPK model with ten compartments
      was developed. An in vitro-in vivo extrapolation technique was used to scale
      clearance in children for clobazam and norclobazam and clearance parameters for
      stiripentol were obtained from fitting. Other drug and system parameters were
      obtained from the literature. RESULTS: The tissue/blood partition coefficients
      adequately predict observed volume of distribution for clobazam and stiripentol.
      In a clinical study in children where clobazam was administered alone and co
      administered with stiripentol, the predicted and observed minimum concentration
      at steady state (mean and 95% confidence interval) during clobazam monotherapy
      were 0.19 (0.05-0.49 mg/L) and 0.20 (0.17-0.23 mg/L), respectively, and predicted
      and observed norclobazam concentrations were 0.49 (0.16-1.38 mg/L) and 0.95 (0.91
      0.99 mg/L), respectively. From an interaction study with stiripentol the
      predicted stiripentol concentration was 10.12 (2.51-39.36 mg/L) and the observed
      concentration was 10.0 (8.3-11.7 mg/L); the predicted clobazam concentration was
      0.29 (0.07-1.05 mg/L) and the observed concentration was 0.31 (0.24-0.38 mg/L);
      and the predicted norclobazam concentration was 2.30 (0.45-5.53 mg/L) and the
      observed concentration was 4.32 (3.77-4.87 mg/L). CONCLUSIONS: The PBPK model
      adequately described observed data and the extent of interaction between
      clobazam/norclobazam and stiripentol.

PMID- 25052508
TI  - Periodontal ligament strain induced by different orthodontic bracket removal
      techniques: nonlinear finite-element comparison study.
AB  - OBJECTIVES: The goal of this work was to biomechanically analyze several
      different methods of bracket debonding and compare the strain they induce in the
      periodontal ligament (PDL). METHODS: The CT dataset of an anatomical specimen was
      divided into four segmental models of the mandible. Each model covered one tooth
      (32, 42, 44, and 47). One of these teeth (32) was characterized by marked loss of
      periodontal attachment. After suitable finite-element models were generated,
      material properties were defined as nonlinear for PDL and anisotropic for the
      alveolar bone. This was followed by simulating four bracket debonding techniques:
      frontal and lateral torquing, bracket-wing compression, and shear stress applied
      with specially designed pliers. RESULTS: The greatest strain was measured at the
      periodontally compromised tooth site 32 in response to frontal and lateral
      torquing. Both techniques also resulted in great strain around the other three
      teeth. Strain was markedly lower with the shear technique and virtually
      negligible with the compression technique. All simulated tooth sites confirmed
      the PDL-sparing effect of bracket-wing compression. CONCLUSION: The severity of
      PDL strain during orthodontic bracket removal depends on the debonding method
      used. The technique of compressing the bracket wings appears to trigger the
      smallest effect on PDL. Clinical studies should be undertaken to confirm these
      findings.

PMID- 25052509
TI  - Treatment of patients with suspected brain tuberculoma before or without
      bacteriologic confirmation in endemic places: report of two cases.

PMID- 25052510
TI  - Neurophysiologic evaluation of infants with congenital hypothyroidism before and
      after treatment.
AB  - We performed a systematic neurophysiological evaluation of newborns-infants newly
      diagnosed with congenital hypothyroidism and started on replacement therapy, in
      order to document the maturation of visual, auditory and somesthetic pathways and
      to evaluate the influence of treatment. Twenty-one patients (9 boys, 12 girls)
      were studied. They underwent neurophysiological evaluation consisting of visual,
      auditory, and somatosensory evoked potentials at diagnosis, as well as 6 and 12
      months after initiation of treatment. At the time of diagnosis, 47.61 % of the
      patients had abnormal evoked potentials, with visual evoked potentials being most
      commonly abnormal. Twelve months after the onset of treatment, abnormal evoked
      potentials were detected in 33.3 % of the patients. In newly diagnosed infants
      with congenital hypothyroidism there is a high relevance of abnormal evoked
      potentials (47.61 %) at the time of diagnosis, declining with time and not
      correlating with the severity of the disease at diagnosis, the time of diagnosis
      or the initial dose of thyroxine.

PMID- 25052511
TI  - In the era of total mesorectal excision: adjuvant radiotherapy may be unnecessary
      for pT3N0 rectal cancer.
AB  - BACKGROUND: Due to the Total Mesorectal Excision (TME) surgery made a good local
      control,the role of radiotherapy in the treatment of pT3N0 rectal cancer is
      debated and whether this group of patiens were overtreated has been a controversy
      recently. This study aimed to evaluate the value of adjuvant radiation after TME
      and survival outcome for patients with pT3N0 rectal adenocarcinoma. METHODS: From
      January 2003 to December 2011, a total of 141 patients with pT3N0 rectal cancer
      after radical resection with the principle of Total Mesorectal Excision (TME)
      were enrolled. Among them, 42 patients (29.8%) got adjuvant chemotherapy (CT) and
      the remaining cohort received chemoradiotherapy (CRT). The 5-year overall
      survival rate (OS), 5-year disease free survival rate (DFS), 5-year local
      recurrence free survival rate (LRFS), 5-year local recurrence rate (LRR) and the
      prognostic factor of this cohort were analyzed. RESULTS: The median follow-up
      interval time was 44 months. The 5-year OS and DFS rates were 82.4% and 71.9% for
      the whole group. There were no significant differences in 5-year OS (83.3% vs
      72.4%, P = 0.931) or LRFS rates (81.7% vs 74.5%, P = 0.157) for patients between
      CT group and CRT group. Multivariate cox regression analysis suggests that
      preoperative serum CEA level, number of lymph nodes inspected, perirectal fat
      infiltration were independent prognostic factors for 5-year DFS. The recurrence
      rate was not affected by radiotherapy for patients with lower and midrectal
      cancer. CONCLUSIONS: For the patients with pT3N0 rectal cancer, addition
      radiation after TME surgery made no significant differences in survival rate and
      local recurrence rate. The effect of adjuvant radiotherapy needs further
      evaluation.

PMID- 25052512
TI  - Cost analysis of mandibular distraction versus tracheostomy in neonates with
      Pierre Robin sequence.
AB  - OBJECTIVE: To evaluate costs associated with surgical treatment for neonates with
      Pierre Robin sequence (PRS). STUDY DESIGN: Retrospective cohort study. SETTING:
      Cincinnati Children's Hospital Medical Center. SUBJECTS AND METHODS: With
      Institutional Review Board approval, we retrospectively studied neonates with PRS
      treated from 2001 to 2009 with either tracheostomy (Trach), mandibular
      distraction (MD), or Trach with subsequent MD (Trach+MD). Actual charges over a 3
      year period associated with operative costs, hospital stay, imaging and sleep
      studies, clinic visits, and related emergency room visits were collected. Home
      tracheostomy care charges were estimated individually for each patient. Charges
      were compared using regression and appropriate statistical analyses. RESULTS:
      Forty-seven neonates were included in the study (MD, n = 26; Trach, n = 12;
      Trach+MD, n = 9). Trach group patients had 2.6-fold higher charges than the MD
      group despite no difference in length of hospital stay. This difference increased
      to 7.3-fold when including home trach care-related costs. Trach+MD group patients
      had longer hospital lengths of stay and higher operation room (OR) fees, but no
      increased total charges compared with the Trach only group. CONCLUSIONS: For
      patients with severe PRS, mandibular distraction provides significant cost
      savings over tracheostomy ($300,000 per patient over 3 years). Increased costs
      with tracheostomy come from greater hospital-related charges, more frequent
      airway procedures, a higher incidence of gastrostomy tube feeds, and home trach
      care costs. A careful examination of long-term outcomes will be critical as
      mandibular distraction continues to gain acceptance for treatment of PRS.

PMID- 25052513
TI  - Stretch of the minimally invasive incision during thyroid and parathyroid
      surgery.
AB  - OBJECTIVE: Identify and quantify changes in length of the skin incision following
      minimally invasive thyroid and parathyroid surgery and determine whether these
      changes persist postoperatively. STUDY DESIGN: Cohort study. SETTING: Tertiary
      care teaching hospital. SUBJECTS AND METHODS: Between July 2012 and June 2013, a
      prospective, nonrandomized study was performed on 44 consecutive patients
      undergoing open cervical minimally invasive thyroidectomy (incision approximately
      6 cm or less) or minimally invasive parathyroidectomy (incision approximately 3
      cm or less). Incision length was measured following initial incision, immediately
      after wound closure, and on postoperative follow-up at 2-week and 14-week visits.
      RESULTS: Thirty-one patients underwent minimally invasive thyroidectomy or
      parathyroidectomy with initial incision lengths ranging from 20 mm to 60 mm.
      Seven patients (21%) underwent total thyroidectomy with a mean length of 45 +/- 8
      mm, 15 patients (44%) underwent unilateral thyroid lobectomy with a mean length
      of 37 +/- 5 mm, and 9 patients (26%) underwent parathyroidectomy with a mean
      length of 28 +/- 2 mm. On average, the skin incision lengthened by 3.0 +/- 0.9 mm
      during surgery representing an intraoperative stretch of 8.0% (P < .0001).
      Incision lengths decreased by an average of 0.3 mm at 2-week postoperative follow
      up (ns) and 6.3 mm at 14-week postoperative follow-up (P < .0001). CONCLUSION:
      Significant intraoperative incision stretch is likely to occur during minimally
      invasive thyroid and parathyroid surgery. Postoperative follow-up data suggest
      that the increase in incision length is not permanent and resolves upon
      postoperative follow-up.

PMID- 25052514
TI  - Framework for advancing otolaryngology: head and neck surgery in Ethiopia.
AB  - The American Academy of Otolaryngology--Head and Neck Surgery and its members
      have shown continuing commitment to improving global otolaryngology care through
      humanitarian and international outreach programs. These efforts, based on a
      surgical mission model, have produced only modest improvements in otolaryngologic
      care in Ethiopia. In cooperation with the Ethiopian Ministry of Health and 2
      Ethiopian medical schools, we present a framework for otolaryngology education
      for the next decade. It recognizes the limitations of the current didactic
      paradigm and aims to use available domestic and international resources to
      improve the quality and availability of head and neck surgical and medical
      services.

PMID- 25052515
TI  - The cost and inpatient burden of treating mandible fractures: a nationwide
      inpatient sample database analysis.
AB  - OBJECTIVE: To discuss patient demographics, hospitalization characteristics, and
      costs associated with the treatment of mandible fractures. STUDY DESIGN: Cross
      sectional study. SETTING: The 2009 Nationwide Inpatient Sample (NIS) database.
      SUBJECTS/METHODS: Patient demographics, hospital characteristics, fracture
      locations, and common comorbidities for patients with isolated mandible fractures
      were analyzed, and variables associated with increased cost and length of
      hospitalization stay were ascertained. RESULTS: A total of 1481 patients were
      identified with isolated mandible fractures. The average age was 32, 85.4% were
      male, 39% were Caucasian, and 25% African American. Forty percent were from the
      lowest median household income quartile, and 77% were uninsured or government
      funded. The average length of stay (LOS) was 2.65 days, and average
      hospitalization cost was $35,804. A statistically significant increased LOS was
      associated with alcohol abuse, drug abuse, mental illness, diabetes mellitus type
      2, cardiovascular disease, HIV, and age over 40. There was a statistically
      significant increased total cost associated with drug abuse, alcohol abuse,
      mental illness, cardiovascular disease, and age over 40. CONCLUSION: The average
      cost for treatment of mandible fractures was $35,804 per person with increased
      expenditures for older patients and those with a history of mental illness,
      cardiovascular disease, or substance abuse. To improve outcomes and reduce
      hospital charges, outpatient resources and inpatient protocols should be
      implemented to address the factors we identified as contributing to higher costs
      and increased hospital stay.

PMID- 25052517
TI  - Chronic hepatitis B virus in young adults: the need for new approaches to
      management.
AB  - One in four patients infected with hepatitis B virus (HBV) at birth or in early
      childhood will develop cirrhosis or hepatocellular carcinoma. Historically,
      guidelines have overlooked treatment in young people, as the immune tolerant
      disease phase is considered synonymous with chronic infection in the young.
      Current treatment aims to suppress HBV replication through long-term
      nucleos(t)ide therapy with little emphasis on virus eradication. To achieve HBsAg
      loss, it is accepted that effective immune control of virus is required,
      mimicking that seen in those who resolve acute HBV infection. We have recently
      challenged the accuracy of a generic immune tolerant state in young people, thus
      raising a potential role for earlier treatment. Here we report on our
      immunological analysis of HBV in young people and the role of a dedicated clinic;
      we make the case for earlier intervention to achieve effective immune control
      leading to better outcomes. 

PMID- 25052516
TI  - Risk of malignancy associated with head and neck CT in children: a systematic
      review.
AB  - OBJECTIVE: To perform a systematic review to evaluate the risk of malignancy
      associated with computed tomography (CT) of the head and/or neck in infants,
      children, and adolescents. DATA SOURCES: Pubmed, EMBASE, and the Cochrane Library
      were assessed from the date of their inception to January 2014. Additionally,
      manual searches of bibliographies were performed and topic experts were
      contacted. REVIEW METHODS: Data were obtained from studies measuring or
      estimating the risks of malignancy associated with radiation from head and/or
      neck CT in pediatric populations according to an a priori protocol. Two
      independent evaluators corroborated the extracted data. RESULTS: There were 16
      criterion-meeting studies that included data from n = 858,815 patients. The
      radiation-related risk of malignancy was estimated using primary patient data for
      both the exposure and outcome in a minority of studies, with most analyses
      utilizing mathematical modeling techniques. The data regarding otolaryngology
      specific studies were limited and suggested a borderline significant increase in
      the risk of all combined cancers after facial CT (incidence rate ratio [IRR] =
      1.14; 95% CI, 1.01-1.28) and neck/spine CT (IRR = 1.13; 95% CI, 1.00-1.28).
      Cohort data suggest that 1 excess brain malignancy occurred after 4000 brain CTs
      (40 mSv per scan) and that the estimated risk in the 10 years following CT
      exposure was 1 brain tumor per 10,000 patients exposed to a 10 mGy scan at less
      than 10 years of age. CONCLUSION: Detailed understanding of any potential
      malignancy risk associated with pediatric imaging of the head and neck furthers
      our ability to engage in rational, shared, informed decision making with families
      considering CT scan.

PMID- 25052518
TI  - Long-term, low-dose exposure to microcystin toxin does not increase the risk of
      liver tumor development or growth in mice.
AB  - AIM: Cyanotoxins are biological toxins produced by cyanobacteria (blue green
      algae) that have been implicated in the pathogenesis of liver tumors. Based on
      acute toxicity studies, the World Health Organization has designated 1.0 MUg/L of
      cyanotoxin-contaminated drinking water as the safe allowable limit for daily oral
      consumption. The aim of this study was to determine whether long-term exposure to
      this concentration of cyanotoxins is capable of initiating or promoting the
      growth of liver tumors. METHODS: In the present study, four groups of adult, male
      CD-1 mice (n = 20/group) were exposed to either drinking water alone (water
      group), drinking water containing 1.0 MUg/L of microcystin-LR (MC-LR group), MC
      LR plus the tumor promoter thioacetamide (MC-LR/TAA group) or thioacetamide alone
      (TAA group). Following 28 weeks of exposure, mice were killed and the livers
      examined for tumor number and size. RESULTS: No tumors were present in the water
      or MC-LR alone groups while five mice in the MC-LR/TAA group and four in the TAA
      alone group developed liver tumors. The mean size of the tumors in the MC-LR/TAA
      and TAA alone groups were similar as were the results of Ki-67 staining, number
      of atypical mitoses and liver cancer gene expression profiles. In vitro MC-LR
      (0.1-1000 MUg/L) exposure did not induce malignant transformation of WB-F344
      hepatic stem cells or increase the proliferative activity or invasiveness of
      PLC/PRF/5 malignant hepatocytes. CONCLUSION: The results of this study suggest
      that long-term, low dose cyanotoxin exposure is unlikely to result in liver tumor
      development or enhance existing tumor growth.

PMID- 25052520
TI  - Single-stranded DNA fragments of insect-specific nuclear polyhedrosis virus act
      as selective DNA insecticides for gypsy moth control.
AB  - This paper focuses on the DNA insecticides as a novel preparation against gypsy
      moth (Lymantria dispar) based on DNA fragments of the anti-apoptotic gene of its
      nuclear polyhedrosis virus. It was found that the external application of a
      solution with two single-stranded DNA fragments from BIR and RING domains of
      LdMNPV (L.dispar multicapsid nuclear polyhedrosis virus) IAP-3 (inhibitor of
      apoptosis) gene induces a significantly higher mortality of gypsy moth
      caterpillars in comparison with the application of the control solutions. This
      effect does not depend on the infection of caterpillars with LdMNPV. The results
      also show that DNA insecticides based on LdMNPV IAP-3 gene fragments can be
      selective in action, and at least are not harmful to tobacco hornworm (Manduca
      sexta) and black cutworm (Agrotis ipsilon). Part of the gypsy moth genome cloned
      with the fragments of BIR and RING domains of LdMNPV IAP-3 gene as primers, has
      an overlap with the corresponding part of the LdMNPV IAP-3 gene and L.dispar IAP
      1 mRNA for an inhibitor of apoptosis protein with the high cover by query, allows
      assuming that we cloned a part of gypsy moth anti-apoptosis gene. This finding
      gives the grounding that proposed here DNA insecticides might act through the
      blocking of the mechanisms involved in post transcriptional expression of insect
      anti-apoptosis genes. The results show the insecticidal potential of the viral
      genome fragments that can be used to create safe and relatively fast-acting DNA
      insecticides to control the quantity of gypsy moth populations, important task
      for forestry and agriculture.

PMID- 25052519
TI  - Motif types, motif locations and base composition patterns around the RNA
      polyadenylation site in microorganisms, plants and animals.
AB  - BACKGROUND: The polyadenylation of RNA is critical for gene functioning, but the
      conserved sequence motifs (often called signal or signature motifs), motif
      locations and abundances, and base composition patterns around mRNA
      polyadenylation [poly(A)] sites are still uncharacterized in most species. The
      evolutionary tendency for poly(A) site selection is still largely unknown.
      RESULTS: We analyzed the poly(A) site regions of 31 species or phyla. Different
      groups of species showed different poly(A) signal motifs: UUACUU at the poly(A)
      site in the parasite Trypanosoma cruzi; UGUAAC (approximately 13 bases upstream
      of the site) in the alga Chlamydomonas reinhardtii; UGUUUG (or UGUUUGUU) at
      mainly the fourth base downstream of the poly(A) site in the parasite
      Blastocystis hominis; and AAUAAA at approximately 16 bases and approximately 19
      bases upstream of the poly(A) site in animals and plants, respectively.
      Polyadenylation signal motifs are usually several hundred times more abundant
      around poly(A) sites than in whole genomes. These predominant motifs usually had
      very specific locations, whether upstream of, at, or downstream of poly(A) sites,
      depending on the species or phylum. The poly(A) site was usually an adenosine (A)
      in all analyzed species except for B. hominis, and there was weak A predominance
      in C. reinhardtii. Fungi, animals, plants, and the protist Phytophthora infestans
      shared a general base abundance pattern (or base composition pattern) of "U-rich
      A-rich-U-rich-Poly(A) site-U-rich regions", or U-A-U-A-U for short, with some
      variation for each kingdom or subkingdom. CONCLUSION: This study identified the
      poly(A) signal motifs, motif locations, and base composition patterns around mRNA
      poly(A) sites in protists, fungi, plants, and animals and provided insight into
      poly(A) site evolution.

PMID- 25052521
TI  - Biochemical mechanisms for metaflumizone resistance in beet armyworm, Spodoptera
      exigua.
AB  - The metaflumizone, which belongs to the class of voltage-dependent sodium channel
      blockers, was registered to control Spodoptera exigua on vegetables in China in
      2009. The present study revealed S. exigua has developed high resistance to this
      novel chemistry insecticide shortly after 2-3 years application in Guangdong
      Province of China. The metabolic mechanisms for metaflumizone resistance in this
      insect were analysed. The inhibitor of esterases greatly potentiates the toxicity
      of this chemical against the field resistant populations. The synergism ratio is
      5.7 and 3.4-fold for S. exigua collected from Huizhou, Guangdong Province in 2011
      and 2012, respectively. The activity of esterases in field populations (HZ12) is
      also significantly greater than that in the susceptible strain, and further
      significantly increased by challenge with metaflumizone for 3 generations.
      However, the inhibitor of P450s or GSTs only has slight synergism on
      metaflumizone toxicity against resistant populations, and there are no obvious
      differences in activities of P450s or GSTs between resistant populations and the
      susceptible strain. These results suggest that esterases might take pivotal role
      in conferring metabolic resistance to metaflumizone in the field populations of
      S. exigua, and P450s or GSTs are not involved in this resistance. Moreover,
      flavin-dependent monooxygenases (FMOs) are discovered to involve in metaflumizone
      resistance in the field populations of S. exigua. The FMO inhibitor, methimazole,
      potentiates metaflumizone toxicity in resistant larva of this species
      substantially. The synergism ratios for methimazole in resistant populations HZ11
      and HZ12 were 3.1 and 1.9, respectively. Enzymatic assays also revealed higher
      FMO activities in resistant populations than in the susceptible strain, and
      successive selection with metaflumizone further increased the FMO activity in the
      field resistant population, but not significantly. The higher FMO activities in
      the older larval stages and in the larval midgut signify the importance of FMO in
      the detoxification of xenobiotic from food sources. The synergism assay and FMO
      activity analysis suggest that FMO contributes to metaflumizone detoxification in
      resistant populations of S. exigua and conferred metaflumizone resistance in S.
      exigua. A novel mechanism for insecticide resistance by insect was proposed.

PMID- 25052522
TI  - In vitro cytotoxic, genotoxic and oxidative stress of cypermethrin on five fish
      cell lines.
AB  - The indiscriminate use of pesticides and herbicides to enhance crop production
      has aroused great concern, because these products are likely to reach the aquatic
      environment, thereby posing a health concern for humans and aquatic species.
      Cypermethrin (CYP), a type II pyrethroid insecticide, is widely used in
      agriculture and for other purposes. Therefore a study was conducted for the
      assessment of cytotoxic, genotoxic and oxidative stress of CYP in IEG, CB, ICG,
      LRG and CSG cell lines at 24h exposure. The cytotoxic effect of CYP in IEG, CB,
      ICG, LRG and CSG cell lines was assessed using MTT, NR, AB and CB assays. Linear
      correlations between each EC50 values, of CYP resulting in 50% inhibition of
      cytotoxicity parameters after 24h exposure to CYP were calculated for IEG, CB,
      ICG, LRG and CSG cell lines using MTT, NR, AB and CB assays. Statistical analysis
      revealed good correlation with R(2)=0.90-0.939 for all combinations between
      endpoints employed. The percentage of DNA damage was assessed by comet assay in
      IEG, CB, ICG, LRG and CSG cells exposed to CYP. The results of antioxidant
      parameters obtained show a significant increase in lipid peroxidation (LPO) level
      and decreased level of GSH, SOD and CAT in IEG, CB, ICG, LRG and CSG cell lines
      after exposure to increasing CYP in a concentration-dependent manner. This work
      proves that fish cell lines could be used not only for cytotoxicity and
      genotoxicity studies but also for studying oxidative stress when exposed to
      environmental contaminants such as pesticides and other pollutants. 

PMID- 25052523
TI  - Glyphosate affects the spontaneous motoric activity of intestine at very low
      doses - in vitro study.
AB  - Glyphosate is an active substance of the most popular herbicides worldwide. Its
      common use results from the belief that it affects exclusively plants. However,
      studies on glyphosate and its trade formulations reveal that it causes numerous
      morphological, physiological and biochemical disturbances in cells and organisms
      of animals, including mammals. Due to the fact that shortly after oral exposure
      glyphosate is detected in the highest amount in small intestine, the aim of this
      study was to evaluate the effect of this compound on the spontaneous motoric
      activity of intestine under in vitro conditions. The experiments were conducted
      on rat jejunum strips under isotonic conditions. The strips were incubated in
      buffered (pH 7.35) and non-buffered (pH 5.2) glyphosate solutions ranged from
      0.003 to 1.7 g/L. The results indicate that glyphosate applied in buffered
      solution affects significantly the spontaneous motoric activity of rat isolated
      jejunum strips. The muscle response is biphasic (miorelaxation accompanied by
      contraction). The contraction is observed already at a dose of 0.003 g/L and the
      first significant biphasic reaction at a dose of 0.014 g/L. The incubation of
      jejunum strips with glyphosate in non-buffered solution (pH 5.2) results in a
      different reaction. The smooth muscle undergoes only persistent relaxation, which
      is stronger than the response to glyphosate solution in pH 7.35. Motility
      disturbances are also observed after glyphosate removal from the incubation
      solution. The gathered data suggests that glyphosate impairs gastrointestinal
      strips' motility at concentration that are noticed in human exposed to non-toxic
      doses of glyphosate.

PMID- 25052524
TI  - Proteomic analysis of zoxamide-induced changes in Phytophthora cactorum.
AB  - In this study, the global proteomic response of Phytophthora cactorum to zoxamide
      was evaluated using a two-dimensional gel electrophoresis (2-DE)-based proteomic
      approach. Among the 21 proteins identified by matrix-assisted laser
      desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS),
      four cytoskeleton-related proteins were down-regulated upon addition of zoxamide.
      Five detoxification metabolism enzymes, seven sugar metabolism proteins and one
      mitochondria-related protein were up-regulated by more than 2-fold in response to
      zoxamide. Taken together, these results suggest that zoxamide can decrease the
      expression of cytoskeleton-related proteins of P. cactorum, resulting in cell
      death; however, the up-regulation of detoxification metabolism-related enzymes
      may protect P. cactorum against zoxamide, and the up-regulation of proteins
      related to sugar metabolism and mitochondria may lead to the generation of more
      energy for detoxification metabolism. These data also suggest that proteomics may
      be useful not only in exploring the mode of action of fungicides but also for
      gaining insight into the resistance mechanisms that pathogens employ against
      fungicides. 

PMID- 25052525
TI  - Assessment of chromosomal damage induced by a deltamethrin-based insecticide in
      fish (Anguilla anguilla L.) - a follow-up study upon exposure and post-exposure
      periods.
AB  - The pyrethroid insecticide Decis(r), containing deltamethrin as active
      ingredient, is among the most popular broad-spectrum biocides, with wide
      application in agriculture and home pest control. The occurrence of deltamethrin
      in the aquatic environment is well-established, but the possible genotoxic
      effects of Decis(r) in non-target organisms, namely fish, remain unknown. Hence,
      this work aimed to evaluate the cytogenetic damaging potential of Decis(r) in
      European eel (Anguilla anguilla L.), adopting the erythrocytic nuclear
      abnormalities (ENAs) assay. In addition, it was intended to investigate the
      damage progression in the post-exposure period. The frequency of immature
      erythrocytes (IE) was also determined to provide indirect information on the
      erythrocyte catabolism and erythropoiesis rate. Fish were exposed to 17.5 and 35
      MUg L(-1) of Decis(r) (equivalent to 0.05 and 0.1 MUg L(-1) of deltamethrin,
      respectively) during 1 and 3 days. Thereafter, fish were transferred to clean
      water and kept for 1, 7 and 14 days. The results demonstrated a clear potential
      to induce chromosomal damage following 3 days exposure, depicted in an ENA
      frequency increase for both Decis(r) concentrations. The transient nature of this
      cytogenetic damage was also demonstrated, as ENA frequency returned to the
      control level 1 and 7 days after cessation of the exposure, respectively for the
      higher and the lower Decis(r) concentration. Moreover, this response pattern
      suggested a rapid metabolization and elimination of the formulation constituents
      by A. anguilla, combined with an increased erythrocyte turnover in fish exposed
      to the higher Decis(r) concentration, as pointed out by the IE frequency rise.
      Overall, the demonstrated genotoxic properties of Decis(r) pointed out increased
      risk factors to fish exposed to this insecticide.

PMID- 25052526
TI  - Genotoxicity of sulcotrione pesticide and photoproducts on Allium cepa root
      meristem.
AB  - Contamination by toxic agents in the environment has become matters of concern to
      agricultural countries. Sulcotrione, a triketone herbicide used to control
      dicotyledonous weeds in maize culture is rapidly photolyzed on plant foliage and
      generate two main photoproducts the xanthene-1,9-dione-3,4-dihydro-6
      methylsulfonyl and 2-chloro-4-mesylbenzoic acid (CMBA). The aim of this study was
      to analyze the potential toxicity of the herbicide and the irradiated herbicide
      cocktail. Cytotoxicity and genotoxicity of non irradiated and irradiated
      sulcotrione were investigated in Allium cepa test. The sulcotrione irradiation
      was monitored under sunlight simulated conditions to reach 50% of
      phototransformation. Concentrations of sulcotrione in the range 5 * 10(-)(9)-5 *
      10(-)(5)M were tested. Cytological analysis of root tips cells showed that both
      non irradiated and irradiated sulcotrione caused a dose-dependent decrease of
      mitotic index with higher cytotoxicity for the irradiated herbicide which can
      lead to 24.2% reduction of mitotic index compared to water control.
      Concomitantly, chromosomal aberrations were observed in A.cepa root meristems.
      Both non irradiated sulcotrione and irradiated sulcotrione induced a dose
      dependent increase of chromosomal abnormalities frequencies to a maximal value of
      33.7%. A saturating effect in anomaly frequencies was observed in meristems
      treated with high concentrations of non irradiated sulcotrione only. These data
      suggest that photolyzed sulcotrione cocktail have a greater cytotoxicity and
      genotoxicity than parent molecule and question about the impact of photochemical
      process on environment.

PMID- 25052527
TI  - Fumigant toxicity and acetylcholinesterase inhibitory activity of 4 Asteraceae
      plant essential oils and their constituents against Japanese termite
      (Reticulitermes speratus Kolbe).
AB  - This study investigated the fumigant toxicity of 4 Asteraceae plant essential
      oils and their constituents against the Japanese termite Reticulitermes speratus
      Kolbe. Fumigant toxicity varied with plant essential oils or constituents,
      exposure time, and concentration. Among the tested essential oils, those from
      Chamaemelum nobile exhibited the strongest fumigant toxicity, followed by those
      from Santolina chamaecyparissus, Ormenis multicaulis, and Eriocephalus
      punctulatus at 2 days after treatment. In all, 15, 24, 19, and 9 compounds were
      identified in the essential oils from C. nobile, E. punctulatus, O. multicaulis,
      and S. chamaecyparissus, respectively, by using gas chromatography, gas
      chromatography-mass spectrometry, or open-column chromatography. The identified
      compounds were tested individually for their fumigant toxicity against Japanese
      termites. Among the test compounds, trans-pinocarveol, caryophyllene oxide,
      sabinene hydrate, and santolina alcohol showed strong fumigant toxicity against
      Japanese termites. Acetylcholinesterase (AChE) inhibition activity of the
      identified compounds from C. nobile, E. punctulatus, O. multicaulis, and S.
      chamaecyparissus essential oils were tested to determine the mode of their
      action. The IC50 values of (+)-alpha-pinene, (-)-limonene, (-)-alpha-pinene, beta
      pinene, and beta-phellandrene against Japanese termite AChE were 0.03, 0.13,
      0.41, 0.42, and 0.67mg/mL, respectively. Further studies are warranted to
      determine the potential of these essential oils and their constituents as
      fumigants for termite control.

PMID- 25052528
TI  - Lyme arthritis of the pediatric lower extremity in the setting of polyarticular
      disease.
AB  - BACKGROUND: Lyme arthritis can be readily treated with use of oral antibiotics
      without any need for surgery. In Lyme-endemic areas, differentiating between Lyme
      arthritis and septic arthritis can be difficult. Laboratory testing for Lyme
      disease often results in a delay in diagnosis because many labs batch-test Lyme
      specimens only two times per week due to lack of equipment or increased expense.
      Delayed diagnosis can lead to unneeded surgery in cases in which the surgeon
      indicates the patient for a joint irrigation and debridement (I & D) for possible
      septic arthritis while waiting for Lyme serology results. The purpose of this
      study was to develop an algorithm for the treatment of patients with possible
      Lyme arthritis, with particular attention to poly-articular involvement. METHODS:
      Thirty-nine patients with poly-articular Lyme arthritis, including ankle
      involvement, were reviewed retrospectively. Patients were included if the ankle
      was involved, if they were less than 18 years of age, and had available
      laboratory information and a serologic diagnosis of Lyme disease. RESULTS: Only
      two patients had isolated ankle involvement; of those with poly-articular
      involvement, 34 patients had ankle/knee involvement. Nine patients presented with
      pain in the ankle with passive range of motion (PROM) (22 %); two (4.8 %) had
      refusal to bear weight, and 10 (24 %) had an antalgic gait. All patients had a
      positive Western blot. Ten patients had a peripheral white blood cell (WBC) count
      >12,500/mm(3) , and 16 patients had an erythrocyte sedimentation rate (ESR) >40
      mm/h. CONCLUSION: Without immediate availability of Lyme serology, the decision
      to perform surgical drainage of a swollen joint in the setting of possible Lyme
      arthritis versus septic bacterial arthritis remains a clinical dilemma. Our data
      suggests that patients presenting with one or fewer Kocher criteria symptoms,
      poly-articular disease, and minimal pain with PROM have Lyme, rather than septic,
      arthritis. These patients can be treated with joint aspiration for cultures,
      appropriate antibiotics for Lyme disease, and careful serial exams while waiting
      for results of Lyme serology rather than immediate surgical I & D.

PMID- 25052529
TI  - Population pharmacokinetics of deferiprone in healthy subjects.
AB  - AIMS: To characterize the pharmacokinetics of deferiprone in healthy subjects
      using a model-based approach and to assess the effect of demographic and
      physiological factors on drug exposure. METHODS: Data from 55 adult healthy
      subjects receiving deferiprone (solution 100 mg ml(-1)) were used for model
      building purposes. A population pharmacokinetic analysis was performed using
      nonmem v.7.2. The contribution of gender, age, weight and creatinine clearance
      (CLcr) on drug disposition was evaluated according to standard forward inclusion,
      backward deletion procedures. Model selection criteria were based on graphical
      and statistical summaries. RESULTS: A one compartment model with first order oral
      absorption was found to describe best the pharmacokinetics of deferiprone.
      Simulated exposure values were comparable with previously published data. Mean
      AUC estimates were 45.8 and 137.4 mg l(-1)  h, whereas Cmax increased from 17.6
      to 26.5 mg l(-1) after administration of 25 and 75 mg kg(-1) doses, respectively.
      Gender differences in the apparent volume of distribution (20%) have been
      identified, which are unlikely to be of clinical relevance. Furthermore,
      simulation scenarios reveal that dose adjustment is required for patients with
      reduced CLcr . Doses of 60, 40 and 25 mg kg(-1) for patients showing mild,
      moderate and severe renal impairment are proposed based on CLcr values of 60-89,
      30-59 and 15-29 ml min(-1), respectively. CONCLUSIONS: Our analysis has enabled
      the assessment of the impact of gender and CLcr on the pharmacokinetics of
      deferiprone. Moreover, it provides the basis for dosing recommendations in renal
      impairment. The implication of these covariates on systemic exposure is currently
      not available in the prescribing information of deferiprone.

PMID- 25052530
TI  - Life-course socio-economic disadvantage and late-life cognitive functioning in
      Taiwan: results from a national cohort study.
AB  - BACKGROUND: Declines in late-life cognitive functioning differ greatly between
      socio-economic status (SES) groups, but little is known about whether these
      effects are related to child and adult SES versus SES effects that accumulate
      over the individual's life course. METHODS: An 18-year longitudinal national
      sample of older adults from Taiwan (n=2944) was used to estimate the effect of
      socio-economic disadvantage over the individual's life course on cognitive
      functioning during late life. Cognitive functioning was assessed using the brief
      Short Portable Mental Status Questionnaire scale. Life-course socio-economic
      disadvantage, as accrued during childhood and adulthood, included measures of
      paternal education and occupation and participant's education and occupation.
      RESULTS: Multivariate analyses using various mixed-effects models showed that the
      effects of childhood SES could be largely explained by adult SES and that
      disadvantageous SES in adulthood further exacerbated declines in late-life
      cognitive functioning (beta=-0.02; p<0.001), even controlling for aging, practice
      and other covariates. Possible factors that are associated with life-course socio
      economic disadvantage and late-life cognitive decline included household income
      and perception of economic strain. CONCLUSIONS: The results suggest a critical
      role for life-course socio-economic disadvantage in late-life cognitive decline
      and that this may be manifested via the inequitable distribution of socio
      economic resources over the individual's life course.

PMID- 25052533
TI  - Perception of weight status in U.S. children and adolescents aged 8-15 years,
      2005-2012.
AB  - Childhood obesity is a major public health problem associated with many adverse
      health outcomes in adulthood (1). During 2011-2012, nearly 17% of children and
      adolescents were obese (2). Weight status misperception occurs when the child's
      perception of their weight status differs from their actual weight status based
      on measured height and weight. Accurate weight status self-perception has been
      linked to appropriate weight control behaviors in youth. The National Health and
      Nutrition Examination Survey (NHANES) data for children and adolescents aged 8-15
      years offers an opportunity to examine weight perception status in this age
      group.

PMID- 25052531
TI  - Orbital tumors in USA: difference in survival patterns.
AB  - INTRODUCTION: There is a wide range of tumors affecting the orbital adnexa. Key
      such tumors include lymphomas, carcinomas, melanomas and rhabdomyosarcomas.
      Several studies have proposed that these histological subtypes differ in their
      survival outcomes. In this study we aim to describe the difference in survival
      outcomes between such subtypes. METHODS: The SEER database was used to gather
      patient information. All 18 SEER registries were used. Patients diagnosed from
      1996 to 2005 were included in the analysis. Observed five-year survival rate was
      calculated using the SEER*Stat software version 8.1.2. Data were extracted into
      IBM SPSS version 20 to generate Kaplan Meier curve for each group. RESULTS: There
      were 2180 patients in the SEER databases who met the selection criteria.
      Lymphomas were the most common histology in adults. The overall five-year
      observed survival for all lymphoma patients was 75.9% (95% CI: 73.7-78.1). There
      was statistically significant difference between observed survival rates of
      lymphoma subtypes. Carcinomas were the second most common tumors. Their five-year
      observed survival rate in our study was 60.4%. There was no statistically
      significant difference between carcinoma subtypes' observed survival rates in the
      20-49 age group, while, in the older age group, the difference was found to be
      statistically significant. Rhabdomyosarcomas were the most common tumors in
      children. The overall five-year observed survival rate for rhabdomyosarcomas
      patients was 89.8%. There was no statistically significant difference between
      observed survival rates of rhabdomyosarcomas subtypes. There was no statistically
      significant difference between relative survival rates according to gender and
      treatment received except within melanomas. CONCLUSION: In adults, lymphomas have
      better survival rates than carcinomas. Whereas the lymphoma subtype can be used
      as a determinant prognostic factor in any age, the carcinoma subtype can be used
      as such a determinant in older age groups only. In children, rhabdomyosarcomas
      are the predominant tumors affecting the orbital adnexa. Further studies are
      needed to determine if the difference between embryonal rhabdomyosarcoma and
      alveolar rhabdomyosarcoma observed survival rates are statistically significant.

PMID- 25052534
TI  - Trichoderma songyi sp. nov., a new species associated with the pine mushroom
      (Tricholoma matsutake).
AB  - A new species, Trichoderma songyi, was found to be associated with the pine
      mushroom (Tricholoma matsutake) in Korea. This species was isolated from three
      different substrates: Tricholoma matsutake basidiomata, as well as roots of Pinus
      densiflora and soil in the fairy ring. Based on its molecular and phenotypic
      characteristics, we demonstrate that Trichoderma songyi is unique and
      distinguishable from closely related species. We performed phylogenetic analyses
      based on two molecular markers, the genes for both translation elongation factor
      1-alpha and the second largest subunit of RNA polymerase II. Phylogenetic
      analyses showed that Trichoderma songyi is closely related to Trichoderma
      koningii aggregate and Trichoderma caerulescens. Morphologically, Trichoderma
      songyi can be distinguished from these closely related taxa by its growth rates,
      colony morphology on PDA in darkness, and coconut-like odour. Due to the economic
      importance of the pine mushroom, the relationship between Trichoderma songyi and
      Tricholoma matsutake should be studied further. 

PMID- 25052535
TI  - Aquimixticola soesokkakensis gen. nov., sp. nov., a novel lipolytic
      alphaproteobacterium isolated from the junction between the ocean and a
      freshwater spring, and reclassification of Roseovarius marinus as Pacificibacter
      marinus comb. nov. and emended description of the genus Pacificibacter.
AB  - A Gram-negative, aerobic, non-flagellated and rod-shaped or ovoid bacterial
      strain, designated DSSK2-3(T), was isolated from the junction between the ocean
      and a freshwater spring at Jeju island, South Korea. Strain DSSK2-3(T) was found
      to grow optimally at 30  degrees C, at pH 7.0-8.0 and in the presence of 2.0-3.0%
      (w/v) NaCl. Neighbour-joining and maximum-likelihood phylogenetic trees based on
      16S rRNA gene sequences revealed that strain DSSK2-3(T) joins the cluster
      comprising the type strains of Pacificibacter maritimus and Roseovarius marinus,
      with which it exhibited the highest sequence similarity values of 96.04 and
      95.75%, respectively. Sequence similarities to the type strains of other
      recognized species were <95.74%. Strain DSSK2-3(T) was found to contain Q-10 as
      the predominant ubiquinone and C(18:1) omega7c as the major fatty acid. The polar
      lipid profile of strain DSSK2-3(T) was found to contain phosphatidylglycerol, an
      unidentified lipid and an unidentified aminolipid as major components, which
      distinguished the strain from those of phylogenetically related taxa. The DNA G+C
      content of strain DSSK2-3(T) was determined to be 60.8 mol%. On the basis of the
      phylogenetic data and the chemotaxonomic and other phenotypic properties, strain
      DSSK2-3(T) is considered to represent a new genus and species within the class
      Alphaproteobacteria, for which the name Aquimixticola soesokkakensis gen. nov.,
      sp. nov. is proposed. The type strain of A. soesokkakensis is DSSK2-3(T) (=KCTC
      42137(T) = CECT 8620(T)). In this study, it is also proposed that R. marinus
      should be reclassified as a member of the genus Pacificibacter and the
      description of the genus Pacificibacter is emended.

PMID- 25052536
TI  - Cost-effectiveness of strategies to improve the utilization and provision of
      maternal and newborn health care in low-income and lower-middle-income countries:
      a systematic review.
AB  - BACKGROUND: Each year almost 3 million newborns die within the first 28 days of
      life, 2.6 million babies are stillborn, and 287,000 women die from complications
      of pregnancy and childbirth worldwide. Effective and cost-effective interventions
      and behaviours for mothers and newborns exist, but their coverage remains
      inadequate in low- and middle-income countries, where the vast majority of deaths
      occur. Cost-effective strategies are needed to increase the coverage of life
      saving maternal and newborn interventions and behaviours in resource-constrained
      settings. METHODS: A systematic review was undertaken on the cost-effectiveness
      of strategies to improve the demand and supply of maternal and newborn health
      care in low-income and lower-middle-income countries. Peer-reviewed and grey
      literature published since 1990 was searched using bibliographic databases,
      websites of selected organizations, and reference lists of relevant studies and
      reviews. Publications were eligible for inclusion if they report on a behavioural
      or health systems strategy that sought to improve the utilization or provision of
      care during pregnancy, childbirth or the neonatal period; report on its cost
      effectiveness; and were set in one or more low-income or lower-middle-income
      countries. The quality of the publications was assessed using the Consolidated
      Health Economic Evaluation Reporting Standards statement. Incremental cost per
      life-year saved and per disability-adjusted life-year averted were compared to
      gross domestic product per capita. RESULTS: Forty-eight publications were
      identified, which reported on 43 separate studies. Sixteen were judged to be of
      high quality. Common themes were identified and the strategies were presented in
      relation to the continuum of care and the level of the health system. There was
      reasonably strong evidence for the cost-effectiveness of the use of women's
      groups, home-based newborn care using community health workers and traditional
      birth attendants, adding services to routine antenatal care, a facility-based
      quality improvement initiative to enhance compliance with care standards, and the
      promotion of breastfeeding in maternity hospitals. Other strategies reported cost
      effectiveness measures that had limited comparability. CONCLUSION: Demand and
      supply-side strategies to improve maternal and newborn health care can be cost
      effective, though the evidence is limited by the paucity of high quality studies
      and the use of disparate cost-effectiveness measures. TRIAL REGISTRATION:
      PROSPERO_ CRD42012003255.

PMID- 25052537
TI  - The shiny corner of the knee: a sign of meniscal osteochondral unit dysfunction.
AB  - OBJECTIVE: The purpose of this retrospective study is to describe the MRI
      findings of the "shiny corner" of the knee (bone marrow lesions at the meniscal
      covered portions of the tibial plateau) and to determine its association with
      compromise of the medial meniscal-osteochondral unit. MATERIALS AND METHODS: A
      retrospective review of 200 knee MRI exams was performed and images were
      evaluated in consensus by two musculoskeletal radiologists. Presence and location
      of a shiny-corner lesion was recorded, which was defined as a focal, peripheral
      hyperintense lesion on fluid-sensitive images at the superior portion of the
      medial tibial plateau. Meniscal and root ligament abnormalities were recorded,
      including tearing, degeneration, and extrusion. RESULTS: Sixty exams demonstrated
      a shiny-corner lesion. Shiny corners involved the medial rim of the medial tibial
      plateau in 50 cases, only involved the posterior rim in seven cases, and only
      involved the anterior rim in two cases. Patients with shiny corners were older
      than patients without shiny corners (mean, 53 years vs. 44 years, p = 0.01). The
      shiny-corner sign was associated with tears of the medial meniscus, root
      ligament, and meniscal extrusion (p < 0.001). The presence of a shiny-corner
      lesion could detect a tear of the medial meniscus or root ligaments with a
      sensitivity, specificity, positive predictive value, and negative predictive
      value of 62, 97, 95, and 75%, respectively. CONCLUSIONS: Shiny-corner lesions of
      the knee are associated with tears of the menisci and root ligaments. This
      observation supports the concept that the menisci protect the underlying covered
      portions of the tibial plateau.

PMID- 25052538
TI  - Diffuse bone marrow sarcoid-like reaction associated with renal cell carcinoma.
AB  - Sarcoid-like reaction has been documented in association with several types of
      malignancy, including renal cell carcinoma. We report the case of a 41-year-old
      man with nonmetastatic renal cell carcinoma and concomitant non-caseating
      granulomas distributed diffusely throughout the bone marrow. The granulomas
      resolved after nephrectomy. As far as we know, this is the first reported case of
      a sarcoid-like reaction primarily involving the bone marrow in association with
      renal cell carcinoma. 

PMID- 25052540
TI  - Orbital schwannoma: a clinicopathologic study.
AB  - The aim of the study was to study the clinical, radiological and
      histopathological characteristics of orbital schwannomas. It is a retrospective
      study conducted at a tertiary eye care hospital. A review of histopathological
      records of the orbital tumors operated between 1993 and 2011 was done. The
      clinical, imaging and histopathological details of cases of orbital schwannoma
      were analyzed. Forty-nine cases of orbital schwannomas identified. The age ranged
      from 8 to 65 years with a female preponderance. The median duration of symptoms
      was 3 years. Computed tomography findings varied from a hypodense to hyperdense
      lesion with nil to marked contrast enhancement. USG demonstrated a defined lesion
      with variable internal reflectivity. Varied proportions of Antoni A and Antoni B
      areas were found on histopathology of the masses. Hypodense or cystic areas on
      imaging significantly correlated with Antoni B areas on histopathology. Orbital
      schwannoma is a rare tumor. The incidence of schwannoma in our institution is 6.5
      %. Variable imaging features were found. The definite diagnosis can be
      established on the basis of histopathological and immunohistochemical studies.

PMID- 25052539
TI  - An eggshell-like mineralized recurrent lesion in the popliteal region after
      treatment of giant cell tumor of the bone with denosumab.
AB  - We report a case of recurrent giant cell tumor of the bone (GCTB) in which
      treatment with denosumab gradually enhanced the eggshell-like mineralization at
      the periphery of the tumor. A 28-year-old male presented with a mass on his left
      distal femur that had enlarged within the past few months. Before curettage, GCTB
      of the distal femur was diagnosed based on histological analysis of a biopsy
      specimen; the tumor consisted of a proliferation of ovoid mononuclear stromal
      cells with evenly scattered multinucleated osteoclast-like giant cells. The tumor
      recurred three times after the initial diagnosis; at the time of the third
      relapse, the patient underwent en bloc resection and reconstruction with a knee
      joint prosthesis. He was also treated with denosumab postoperatively because some
      studies have recently shown the benefits of the receptor activator of nuclear
      factor kappa-B ligand (RANKL) inhibitor denosumab as adjuvant therapy in patients
      with GCTB. Six months after starting adjuvant treatment with denosumab,
      radiography revealed a mineralized nodule >2 cm in diameter at the popliteal
      region; this lesion was considered a soft tissue recurrence of GCTB. Treatment
      with denosumab was continued for another 1.5 years, and the lesion was resected.
      Histological examination showed residual mononuclear stromal cells expressing
      RANKL without multinucleated giant cells surrounded by the peripheral
      mineralization. The patient was successfully treated by complete resection with
      the support of adjuvant treatment with denosumab. 

PMID- 25052541
TI  - A QM/MM study of the reaction mechanism of (R)-hydroxynitrile lyases from
      Arabidopsis thaliana (AtHNL).
AB  - Hydroxynitrile lyases (HNLs) catalyze the conversion of chiral cyanohydrins to
      hydrocyanic acid (HCN) and aldehyde or ketone. Hydroxynitrile lyase from
      Arabidopsis thaliana (AtHNL) is the first R-selective HNL enzyme containing an
      alpha/beta-hydrolases fold. In this article, the catalytic mechanism of AtHNL was
      theoretically studied by using QM/MM approach based on the recently obtained
      crystal structure in 2012. Two computational models were constructed, and two
      possible reaction pathways were considered. In Path A, the calculation results
      indicate that the proton transfer from the hydroxyl group of cyanohydrin occurs
      firstly, and then the cleavage of C1-C2 bond and the rotation of the generated
      cyanide ion (CN(-)) follow, afterwards, CN(-) abstracts a proton from His236 via
      Ser81. The C1-C2 bond cleavage and the protonation of CN(-) correspond to
      comparable free energy barriers (12.1 vs. 12.2 kcal mol(-1)), suggesting that
      both of the two processes contribute a lot to rate-limiting. In Path B, the
      deprotonation of the hydroxyl group of cyanohydrin and the cleavage of C1-C2 bond
      take place in a concerted manner, which corresponds to the highest free energy
      barrier of 13.2 kcal mol(-1). The free energy barriers of Path A and B are very
      similar and basically agree well with the experimental value of HbHNL, a similar
      enzyme of AtHNL. Therefore, both of the two pathways are possible. In the
      reaction, the catalytic triad (His236, Ser81, and Asp208) acts as the general
      acid/base, and the generated CN(-) is stabilized by the hydroxyl group of Ser81
      and the main-chain NH-groups of Ala13 and Phe82.

PMID- 25052542
TI  - The effect of aspartate on the energy metabolism in the liver of weanling pigs
      challenged with lipopolysaccharide.
AB  - PURPOSE: This study was conducted to investigate whether aspartate (Asp) could
      improve liver energy status in the lipopolysaccharide (LPS)-challenged pigs.
      METHODS: Twenty-four weaned pigs were assigned to four treatments: (1)
      nonchallenged control (control diet and saline-treated); (2) LPS-challenged
      control (the same control diet and LPS-challenged); (3) LPS + 0.5% Asp treatment
      (0.5% Asp diet and LPS-challenged); and (4) LPS + 1.0% Asp treatment (a 1.0% Asp
      diet and LPS-challenged). On d 19, the pigs were injected intraperitoneally with
      Escherichia coli LPS at 100 MUg/kg body weight, and the same volume of 0.9% NaCl
      solution, respectively. All pigs were slaughtered at 24 h after LPS or saline
      injection, and the liver was collected for further analysis. RESULTS: Dietary
      supplementation with Asp improved liver energy status evidenced by the increased
      ATP concentration and adenylate energy charges, and the decreased AMP
      concentration and AMP/ATP ratio (p < 0.05). Asp supplementation increased the
      mRNA expression of key enzymes in hepatic glycolysis and tricarboxylic acid (TCA)
      cycle, including pyruvate kinase and citrate synthase (p < 0.05), and had a
      tendency to increase hepatic pyruvate dehydrogenase and isocitrate dehydrogenase
      beta mRNA expression (p < 0.10). In addition, Asp increased the mRNA expressions
      of hepatic AMP-activated protein kinase (AMPK) alpha1, AMPKalpha2, silent
      information regulator (Sirt1), and proliferator-activated receptor-gamma
      coactivator 1alpha (PGC1alpha) (p < 0.05). Moreover, Asp increased AMPKalpha
      phosphorylation (p < 0.05). CONCLUSIONS: These results indicated that dietary
      supplementation of Asp could improve energy status in LPS-injured liver, which
      might result from motivating the metabolism pathway of TCA cycle and glycolysis
      and stimulating the AMPK signaling pathway.

PMID- 25052543
TI  - Metabolic syndrome in Spanish adolescents and its association with birth weight,
      breastfeeding duration, maternal smoking, and maternal obesity: a cross-sectional
      study.
AB  - PURPOSE: The metabolic syndrome (MetS) in adolescents is a growing problem. The
      objectives were to verify the association among early predictors such as birth
      weight, breastfeeding, maternal weight status, smoking during pregnancy, and the
      development of MetS. METHODS: A cross-sectional study was performed of 976
      children and adolescents, 10-15 years of age, at schools in the provinces of
      Granada and Almeria (Spain). For this purpose, we analyzed the physical
      characteristics as well as the biochemical markers of the participants with a
      view to ascertaining the prevalence of the MetS. Relevant data were also
      extracted from the clinical histories of their mothers. RESULTS: It was found
      that 3.85% of the female subjects and 5.38% of the male subjects in the sample
      population suffered from MetS. In both sexes, there was an association between
      birth weight and positive MetS diagnosis (OR 1.27). For both males and females,
      there was an inverse association between the length of time that they had been
      breastfed and positive MetS diagnosis (OR1-3 months 3.16; OR4-6 months 1.70;
      OR(>6 months) 0.13). There was also a significant association between maternal
      weight (OR(overweight )30.79; OR(obesity) 49.36) and cigarette consumption during
      pregnancy (OR 1.47) and the subsequent development of MetS in the children of
      these mothers. CONCLUSIONS: Those subjects born with a higher than average birth
      weight had a greater risk of developing MetS in childhood and adolescence.
      Breastfeeding children for longer than 6 months protected them from MetS in their
      early years as well as in their teens. Other risk factors for MetS were maternal
      smoking during pregnancy as well as maternal overweight and obesity.

PMID- 25052544
TI  - Predicting long-term cardiovascular risk using the mayo clinic cardiovascular
      risk score in a referral population.
AB  - Exercise testing provides valuable information but is rarely integrated to derive
      a risk prediction model in a referral population. In this study, we assessed the
      predictive value of conventional cardiovascular risk factors and exercise test
      parameters in 6,546 consecutive adults referred for exercise testing, who were
      followed for a period of 8.1 +/- 3.7 years for incident myocardial infarction,
      coronary revascularization, and cardiovascular death. A risk prediction model was
      developed, and cross-validation of model was performed by splitting the data set
      into 10 equal random subsets, with model fitting based on 9 of the 10 subsets and
      testing in of the remaining subset, repeated in all 10 possible ways. The best
      performing model was chosen based on measurements of model discrimination and
      stability. A risk score was constructed from the final model, with points
      assigned for the presence of each predictor based on the regression coefficients.
      Using both conventional risk factors and exercise test parameters, a total of 9
      variables were identified as independent and robust predictors and were included
      in a risk score. The prognostic ability of this model was compared with that of
      the Adult Treatment Panel III model using the net reclassification and integrated
      discrimination index. From the cross-validation results, the c statistic of 0.77
      for the final model indicated strong predictive power. In conclusion, we
      developed, tested, and internally validated a novel risk prediction model using
      exercise treadmill testing parameters. 

PMID- 25052545
TI  - Influence of dietary saturated fat intake on endothelial fibrinolytic capacity in
      adults.
AB  - Approximately 50% of middle-aged and older adults in the United States regularly
      consume a diet high in saturated fat. High dietary saturated fat intake has been
      linked to promote atherothrombotic vascular disease. We tested the hypothesis
      that endothelial fibrinolytic function is diminished in middle-aged and older
      adults who habitually consume a diet high in saturated fat. Twenty-four healthy,
      sedentary middle-aged, and older adults (54 to 71 years) were studied: 10 (8 men
      and 2 women) with a dietary saturated fat intake <10% (lower saturated fat) of
      total calories and 14 (9 men and 5 women) with a dietary saturated fat intake
      >=10% of total calories (high saturated fat). Net endothelial release of tissue
      type plasminogen activator (t-PA), the primary activator of fibrinolysis, was
      determined, in vivo, in response to intrabrachial infusions of bradykinin (12.5
      to 50.0 ng/100 ml tissue/min) and sodium nitroprusside (1.0 to 4.0 MUg/100 ml
      tissue/min). Capacity of the endothelium to release t-PA in response to
      bradykinin was ~30% less (p <0.05) in the high (from -0.7 +/- 0.6 to 36.9 +/- 3.3
      ng/100 ml tissue/min) compared with the lower (from -0.3 +/- 0.3 to 53.4 +/- 7.8
      ng/100 ml tissue/min) dietary saturated fat group. Moreover, total amount of t-PA
      released was significantly less (~30%) (201 +/- 22 vs 274 +/- 29 ng/100 ml
      tissue) in the adults who reported consuming a diet high in saturated fat. These
      results indicate that the capacity of the endothelium to release t-PA is lower in
      middle-aged and older adults who habitually consume a diet high in saturated fat.
      In conclusion, endothelial fibrinolytic dysfunction may underlie the increased
      atherothrombotic disease risk with a diet high in saturated fat. 

PMID- 25052546
TI  - Battery-operated, portable, and flexible air microplasma generation device for
      fabrication of microfluidic paper-based analytical devices on demand.
AB  - A portable microplasma generation device (MGD) operated in ambient air is
      introduced for making a microfluidic paper-based analytical device (MUPAD) that
      serves as a primary healthcare platform. By utilizing a printed circuit board
      fabrication process, a flexible and lightweight MGD can be fabricated within 30
      min with ultra low-cost. This MGD can be driven by a portable power supply (less
      than two pounds), which can be powered using 12 V-batteries or ac-dc converters.
      This MGD is used to perform maskless patterning of hydrophilic patterns with sub
      millimeter spatial resolution on hydrophobic paper substrates with good pattern
      transfer fidelity. Using this MGD to fabricate MUPADs is demonstrated. With a
      proper design of the MGD electrode geometry, MUPADs with 500-MUm-wide flow
      channels can be fabricated within 1 min and with a cost of less than $USD
      0.05/device. We then test the MUPADs by performing quantitative colorimetric
      assay tests and establish a calibration curve for detection of glucose and
      nitrite. The results show a linear response to a glucose assay for 1-50 mM and a
      nitrite assay for 0.1-5 mM. The low cost, miniaturized, and portable MGD can be
      used to fabricate MUPADs on demand, which is suitable for in-field diagnostic
      tests. We believe this concept brings impact to the field of biomedical analysis,
      environmental monitoring, and food safety survey. 

PMID- 25052547
TI  - Is there evidence to support multidisciplinary healthcare working in
      rheumatology? A systematic review of the literature.

PMID- 25052548
TI  - Mealtime Disruption and Caregiver Stress in Referrals to an Outpatient Feeding
      Clinic.
AB  - BACKGROUND: This investigation explores the feeding behaviors, comorbidities, and
      parenting stress in young children referred to an outpatient feeding clinic.
      MATERIALS AND METHODS: Eligible participants (n =72) were primary caretakers of
      children ages 2-6 years referred to an interdisciplinary outpatient feeding
      disorder clinic, subcategorized according to the absence (n = 18) or presence (n
      = 54) of caretaker-reported medical or developmental comorbidities. This group
      was compared with an equivalent control sample of caretakers of age-matched
      children (n = 72). Measures included the Children's Eating Behavior Inventory
      (CEBI) and the Parenting Stress Index-Short Form (PSI-SF). RESULTS: The CEBI and
      PSI scores were higher in the feeding disorder group than in the control group.
      PSI total was incrementally increased for control vs feeding disorder without
      comorbidity vs feeding disorder with comorbidity. CONCLUSION: Increased
      maladaptive behaviors and parenting stress were evident in children with feeding
      disorder regardless of the presence of comorbidity. Parenting stress was
      exacerbated by the presence of comorbidity.

PMID- 25052549
TI  - Growth factors have a protective effect on neomycin-induced hair cell loss.
AB  - We have demonstrated that selected growth factors are involved in regulating
      survival and proliferation of progenitor cells derived from the neonatal rat
      organ of Corti (OC). The protective and regenerative effects of these defined
      growth factors on the injured organ of Corti were therefore investigated. The
      organ of Corti dissected from the Wistar rat pups (P3-P5) was split into apical,
      middle, and basal parts, explanted and cultured with or without neomycin and
      growth factors. Insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2
      (FGF-2), and epidermal growth factor (EGF) protected the inner hair cells (IHCs)
      and outer hair cells (OHCs) from neomycin ototoxicity. Using EGF, IGF-1, and FGF
      2 alone induced no protective effect on the survival of auditory hair cells.
      Combining 2 growth factors (EGF + IGF-1, EGF + FGF-2, or IGF-1 + FGF-2) gave
      statistically protective effects. Similarly, combining all three growth factors
      effectively protected auditory hair cells from the ototoxic insult. None of the
      growth factors induced regeneration of hair cells in the explants injured with
      neomycin. Thus various combinations of the three defined factors (IGF-1, FGF-2,
      and EGF) can protect the auditory hair cells from the neomycin-induced ototoxic
      damage, but no regeneration was seen. This offers a possible novel approach to
      the treatment of hearing loss.

PMID- 25052550
TI  - Phosphodiesterase type 5 inhibitors for the treatment of post-nerve sparing
      radical prostatectomy erectile dysfunction in men.
AB  - Prostate cancer (PCa) is the most common solid neoplasm diagnosed in developed
      countries. Nerve-sparing radical prostatectomy (NS-RP) has been widely accepted
      as the best choice treatment for localised PCa. However, erectile dysfunction
      (ED) and urinary incontinence are commonly observed after NS-RP. Using meta
      analysis, we examined if phosphodiesterase type 5 inhibitors (PDE5-Is) could
      improve the symptoms of ED in patients undergoing NS-RP. This review contained
      seven randomised placebo-controlled trials with a total of 2,655 male patients.
      Patients in PDE5-Is group showed significant improvement in the International
      Index of Erectile Function-Erectile Function domain score (IIEF-EF), Global
      Assessment Questionnaire (GAQ), Sexual Encounter Profile question 2 (SEP-2) and
      SEP-3. Although the incidence of treatment-emergent adverse events (TEAEs) were
      high in both groups (56.44% vs. 40.63%), the safety profile were acceptable, with
      low incidence of discontinuation rate due to adverse events. Therefore, PDE5-Is
      are recommended for the treatment of post-NS-RP ED. Patients should be informed
      of possible adverse events. 

PMID- 25052551
TI  - Evaluation of clinical trial eligibility and prognostic indices in a population
      based cohort of systemic peripheral T-cell lymphomas from the Danish Lymphoma
      Registry.
AB  - Clinical trials (CTs) are needed to improve the outcome for peripheral T-cell
      lymphomas (PTCL), and accrual into CTs is one of the main recommendations in
      international treatment guidelines. The use of risk-adapted strategies has been
      suggested as a way to optimize treatment outcome in PTCL. The aim of the present
      study was to evaluate CT eligibility and selected prognostic indices in a
      population-based PTCL cohort of 481 PTCL patients identified from the Danish
      Lymphoma Registry in the period 2000-2010. According to five predefined
      parameters (age, performance status, P-creatinine, P-ALAT and measurable tumour
      lesion), patients were subdivided into four groups: 'younger fit', 'elderly fit',
      'frail' and 'not CT eligible'. International prognostic index (IPI), prognostic
      index for T-cell lymphoma (PIT) and anaplastic lymphoma kinase (ALK) protein
      expression were tested at subtype-specific level. Overall, 41% of the patients
      were considered eligible for interventional CTs implicating curatively intended
      multiagent chemotherapy, including, if considered appropriate, consolidating stem
      cell transplantation (SCT), as part of the upfront management strategy. Moreover,
      28% was elderly fit and eligible for interventional CT, including those with SCT
      as part of the trial design. Approximately 7% were defined as 'too frail' for
      aggressive treatment schedules, whereas 24% were deemed not to be eligible for
      any CT. Both overall and progression-free survivals were effectively predicted by
      IPI and PIT (p < 0.001). ALK-positive anaplastic large cell lymphoma patients
      were significantly younger (median age 40 vs. 62, p < 0.001) and had a better
      outcome than their ALK-negative counterparts (p < 0.001). However, ALK expression
      lost its prognostic significance when adjusting for age. In a population-based
      cohort of adult Caucasian PTCL patients, approximately half were eligible for
      multiagent chemotherapy with or without consolidating SCT. Both IPI and PIT are
      useful prognostic indices in all 'primary nodal' PTCL entities. The prognostic
      value of ALK protein expression in anaplastic large cell lymphoma is
      significantly downsized when adjusting for age.

PMID- 25052552
TI  - Associations of non-high density lipoprotein cholesterol and traditional blood
      lipid profiles with hyperuricemia among middle-aged and elderly Chinese people: a
      community-based cross-sectional study.
AB  - BACKGROUND: Increased serum uric acid (SUA) is associated with dyslipidemia.
      However, there are conflicting data about the role of single lipid species
      including non-high density lipoprotein cholesterol (non-HDL-C) in promoting SUA
      accumulation. Here, we aimed to compare non-HDL-C with other traditional blood
      lipid profiles in relation to hyperuricemia in a middle-aged and elderly Chinese
      population. METHODS: Data was collected from 9580 participants undergoing routine
      physical examinations in Xiangcheng district of Suzhou. SUA, total cholesterol
      (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high
      density lipoprotein cholesterol (HDL-C) were examined for all participants. Non
      HDL-C was calculated by subtracting HDL-C from TC. The associations of blood
      lipid profiles with hyperuricemia were examined in men and women, respectively.
      The areas under Receiver Operating Characteristic (ROC) curves (AUCs) were
      compared to assess the discriminatory value of blood lipid parameters for
      predicting hyperuricemia. RESULTS: All blood lipid parameters significantly
      correlated with SUA (all P values <0.001). The correlation coefficient between
      SUA and TG was the highest in both genders. The correlation coefficient of non
      HDL-C was higher than HDL-C in males and was higher than TC and LDL-C but
      followed HDL-C in females. In male group, AUC of TG (0.659) was greater than that
      of non-HDL-C (0.595) (P values <0.001). The AUC values of HDL-C, TC and LDL-C
      were lower; respectively 0.581, 0.559 and 0.552. In female group, AUC was highest
      for TG (0.678) followed by HDL-C (0.616), non-HDL-C (0.610), LDL-C (0.559) and TC
      (0.557) (all P values<0.001). CONCLUSIONS: In both genders, serum TG has the
      strongest association with hyperuricemia among blood lipid parameters. Non-HDL-C
      is also significantly associated with hyperuricemia.

PMID- 25052553
TI  - BMP signaling modulation attenuates cerebral arteriovenous malformation formation
      in a vertebrate model.
AB  - Cerebral arteriovenous malformations (AVMs) are vascular anomalies that carry a
      high risk of stroke and death. To test potential AVM therapies, a reverse
      genetics approach was used to model AVMs in zebrafish. Antisense morpholino
      oligonucleotides were used to knockdown activin receptor-like kinase I (alk1),
      which encodes a transforming growth factor (TGF)-beta family type I receptor
      implicated in a subset of human AVMs. Knockdown of alk1 caused a spectrum of
      morphologic, functional, and molecular defects that resemble those seen in humans
      with AVMs. It was found that losartan, an angiotensin II receptor antagonist,
      attenuated abnormal blood vessel morphology and systemic manifestations of high
      output arteriovenous shunting in vivo. SMAD1 phosphorylation was significantly
      decreased in alk1 morphants compared with uninjected organisms (0.189+/-0.0201,
      0.429+/-0.0164, P=0.0002). After treatment, morphant SMAD1 levels approached
      uninjected levels (0.326+/-0.0360, P=0.0355) and were significantly higher than
      those seen in the morphant-control group (P=0.0294). These data suggest that
      modulating the BMP signaling pathway with losartan, a drug in widespread clinical
      use in humans as an antihypertensive, may have the potential to be further
      evaluated as a therapeutic strategy for patients with AVMs. 

PMID- 25052554
TI  - A cognitive rehabilitation paradigm effective in male rats lacks efficacy in
      female rats.
AB  - Cognitive dysfunction, as a consequence of dementia, is a significant cause of
      morbidity lacking efficacious treatment. Females comprise at least half of this
      demographic but have been vastly underrepresented in preclinical studies. The
      current study addressed this gap by assessing the protective efficacy of physical
      exercise and cognitive activity on learning and memory outcomes in a rat model of
      vascular dementia. Forty ovariectomized Sprague-Dawley rats (~6 months old) were
      exposed to either a diet high in saturated fats and refined sugars or standard
      laboratory chow and underwent either chronic bilateral carotid occlusion or Sham
      surgery. Learning and memory abilities were evaluated using standard cognitive
      outcomes over the ensuing 6 months, followed by histologic analyses of
      hippocampal CA1 neurons. In Experiment 1, we confirmed hypoperfusion-induced
      cognitive dysfunction using a 2 * 2 (Surgery * Diet) experimental design, without
      alterations in hippocampal architecture. In Experiment 2, hypoperfused animals
      were either exposed to alternating days of physical (wheel running) and cognitive
      activity (modified Hebb-Williams maze) or sedentary housing. In contrast to
      males, this combination rehabilitation paradigm did not improve cognition or
      histopathologic outcomes in hypoperfused animals. These findings, highlighting
      differences between female and male animals, show the necessity of including both
      sexes in preclinical experimentation. 

PMID- 25052555
TI  - Cerebral vascular leak in a mouse model of amyloid neuropathology.
AB  - In Alzheimer's disease (AD), there is increasing evidence of blood-brain barrier
      (BBB) compromise, usually observed as 'microbleeds' correlated with amyloid
      plaque deposition and apoE-E4 status, raising the possibility of nanotherapeutic
      delivery. Molecular probes have been used to study neurovascular leak, but this
      approach does not adequately estimate vascular permeability of nanoparticles. We
      therefore characterized cerebrovascular leaks in live APP+ transgenic animals
      using a long circulating ~100 nm nanoparticle computed tomography (CT) contrast
      agent probe. Active leaks fell into four categories: (1) around the dorsomedial
      cerebellar artery (DMCA), (2) around other major vessels, (3) nodular leaks in
      the cerebral cortex, and (4) diffuse leaks. Cortical leaks were uniformly more
      frequent in the transgenic animals than in age-matched controls. Leaks around
      vessels other than the DMCA were more frequent in older transgenics compared with
      younger ones. All other leaks were equally prevalent across genotypes independent
      of age. Ten days after injection, 4 to 5 MUg of the dose was estimated to be
      present in the brain, roughly a half of which was in locations other than the
      leaky choroid plexus, and associated with amyloid deposition in older animals.
      These results suggest that amyloid deposition and age increase delivery of
      nanoparticle-borne reagents to the brain, in therapeutically relevant amounts. 

PMID- 25052557
TI  - Brain BDNF levels elevation induced by physical training is reduced after
      unilateral common carotid artery occlusion in rats.
AB  - We investigated the contribution of blood flow elevation in the
      cerebrovasculature to physical training-induced brain-derived neurotrophic factor
      (BDNF) levels elevation in the brain. Brain-derived neurotrophic factor protein
      levels were measured in the motor cortex 24 h after the last session of a forced
      treadmill walking (30 minutes a day, 18 m/minute for 7 consecutive days).
      Unilateral common carotid artery occlusion and modulation of exercise intensity
      (0 versus -10% inclination of the treadmill) were used as strategies to reduce
      the (normal) elevation of flow in the cerebrovasculature occurring during
      exercise. Administration of N-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg
      before each exercise sessions) and genetic hypertension (spontaneously
      hypertensive rats) were used as approaches to reduce stimulation of nitric oxide
      production in response to shear stress elevation. Vascular occlusion totally and
      partially abolished the effect of physical training on BDNF levels in the
      hemisphere ipsilateral and contralateral to occlusion, respectively. BDNF levels
      were higher after high than low exercise intensity. In addition, both genetic
      hypertension and L-NAME treatment blunted the effects of physical training on
      BDNF. From these results, we propose that elevation of brain BDNF levels elicited
      by physical training involves changes in cerebral hemodynamics. 

PMID- 25052556
TI  - Capillary transit time heterogeneity and flow-metabolism coupling after traumatic
      brain injury.
AB  - Most patients who die after traumatic brain injury (TBI) show evidence of
      ischemic brain damage. Nevertheless, it has proven difficult to demonstrate
      cerebral ischemia in TBI patients. After TBI, both global and localized changes
      in cerebral blood flow (CBF) are observed, depending on the extent of diffuse
      brain swelling and the size and location of contusions and hematoma. These
      changes vary considerably over time, with most TBI patients showing reduced CBF
      during the first 12 hours after injury, then hyperperfusion, and in some patients
      vasospasms before CBF eventually normalizes. This apparent neurovascular
      uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen
      diffusion into tissue, or microthrombosis. Capillary compression by astrocytic
      endfeet swelling is observed in biopsies acquired from TBI patients. In animal
      models, elevated intracranial pressure compresses capillaries, causing
      redistribution of capillary flows into patterns argued to cause functional
      shunting of oxygenated blood through the capillary bed. We used a biophysical
      model of oxygen transport in tissue to examine how capillary flow disturbances
      may contribute to the profound changes in CBF after TBI. The analysis suggests
      that elevated capillary transit time heterogeneity can cause critical reductions
      in oxygen availability in the absence of 'classic' ischemia. We discuss
      diagnostic and therapeutic consequences of these predictions. 

PMID- 25052558
TI  - Juvenile traumatic brain injury induces long-term perivascular matrix changes
      alongside amyloid-beta accumulation.
AB  - In our juvenile traumatic brain injury (jTBI) model, emergence of cognitive
      dysfunctions was observed up to 6 months after trauma. Here we hypothesize that
      early brain injury induces changes in the neurovascular unit (NVU) that would be
      associated with amyloid-beta (Abeta) accumulation. We investigated NVU changes
      for up to 6 months in a rat jTBI model, with a focus on the efflux protein P
      glycoprotein (P-gp) and on the basement membrane proteins perlecan and
      fibronectin, all known to be involved in Abeta clearance. Rodent-Abeta staining
      is present and increased after jTBI around cerebral blood microvessels, and the
      diameter of those is decreased by 25% and 34% at 2 and 6 months, respectively,
      without significant angiogenesis. P-glycoprotein staining in endothelium is
      decreased by 22% and parallels an increase of perlecan and fibronectin staining
      around cerebral blood vessels. Altogether, these results strongly suggest that
      the emergence of long-term behavioral dysfunctions observed in rodent jTBI may be
      related to endothelial remodeling at the blood-brain barrier alongside vascular
      dysfunction and altered Abeta trafficking. This study shows that it is important
      to consider jTBI as a vascular disorder with long-term consequences on cognitive
      functions. 

PMID- 25052559
TI  - Active cigarette smoking, variants in carcinogen metabolism genes and breast
      cancer risk among pre- and postmenopausal women in Ontario, Canada.
AB  - Cigarette smoking is strongly associated with various diseases including many
      cancers; however, evidence regarding breast cancer risk remains inconclusive with
      some studies reporting no association, and others an increased risk with long
      duration and early initiation of smoking. Genetic variation in carcinogen
      metabolizing enzymes may modify these associations. Breast cancer cases were
      identified from the Ontario Cancer Registry (OCR) during 2003-2004 and population
      controls through random digit dialing methods. All subjects completed self
      administered questionnaires. Subsequently, saliva samples were obtained from
      cases (N = 1,776) and controls (N = 1,839) for deoxyribonucleic acid (DNA)
      extraction. Multivariate logistic regression was used to estimate odds ratio (OR)
      and 95% confidence intervals (CI) for active smoking variables, and interactions
      were assessed between smoking and 36 carcinogen-metabolizing candidate gene
      variants. No statistically significant association was found between active
      smoking and breast cancer risk among all women nor when stratified by menopausal
      status; however, nonsignificant increased premenopausal breast cancer risk was
      observed among current smokers and women smoking before first pregnancy. Several
      statistically significant interactions were observed between smoking and genetic
      variants (CYP1A2 1548C>T, CYP1A1 3801T>C, CYP1B1 4326G>C, NAT1 c.-85-1014T>A,
      UGT1A7 W208R 622T>C, SOD2 c.47T>C, GSTT1 deletion). However, in analyses
      stratified by these genotypes, smoking ORs had wide confidence intervals (and
      with few exceptions included 1.0) making interpretations difficult. Active
      smoking was not associated with breast cancer risk, although several significant
      interactions were observed between smoking, carcinogen-metabolizing genetic
      variants, and breast cancer risk.

PMID- 25052560
TI  - Toward online adaptive hyperthermia treatment planning: correlation between
      measured and simulated specific absorption rate changes caused by phase steering
      in patients.
AB  - PURPOSE: Hyperthermia is the clinical application of heat, in which tumor
      temperatures are raised to 40 degrees C to 45 degrees C. This proven radiation
      and chemosensitizer significantly improves clinical outcome for several tumor
      sites. Earlier studies of the use of pre-treatment planning for hyperthermia
      showed good qualitative but disappointing quantitative reliability. The purpose
      of this study was to investigate whether hyperthermia treatment planning (HTP)
      can be used more reliably for online adaptive treatment planning during
      locoregional hyperthermia treatments. METHODS AND MATERIALS: This study included
      78 treatment sessions for 15 patients with non-muscle-invasive bladder cancer. At
      the start of treatments, temperature rise measurements were performed with 3
      different antenna settings optimized for each patient, from which the absorbed
      power (specific absorption rate [SAR]) was derived. HTP was performed based on a
      computed tomography (CT) scan in treatment position with the bladder catheter in
      situ. The SAR along the thermocouple tracks was extracted from the simulated SAR
      distributions. Correlations between measured and simulated (average) SAR values
      were determined. To evaluate phase steering, correlations between the changes in
      simulated and measured SAR values averaged over the thermocouple probe were
      determined for all 3 combinations of antenna settings. RESULTS: For 42% of the
      individual treatment sessions, the correlation coefficient between measured and
      simulated SAR profiles was higher than 0.5, whereas 58% showed a weak correlation
      (R of <0.5). The overall correlation coefficient between measured and simulated
      average SAR was weak (R=0.31; P<.001). The measured and simulated changes in
      average SAR after adapting antenna settings correlated much better (R=0.70;
      P<.001). The ratio between the measured and simulated quotients of maximum and
      average SARs was 1.03 +/- 0.26 (mean +/- SD), indicating that HTP can also
      correctly predict the relative amplitude of SAR peaks. CONCLUSIONS: HTP can
      correctly predict SAR changes after adapting antenna settings during hyperthermia
      treatments. This allows online adaptive treatment planning, assisting the
      operator in determining antenna settings resulting in increased tumor
      temperatures.

PMID- 25052562
TI  - Survival outcome after stereotactic body radiation therapy and surgery for stage
      I non-small cell lung cancer: a meta-analysis.
AB  - PURPOSE: This study compared treatment outcomes of stereotactic body radiation
      therapy (SBRT) with those of surgery in stage I non-small cell lung cancer
      (NSCLC). METHODS AND MATERIALS: Eligible studies of SBRT and surgery were
      retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane
      library databases from 2000 to 2012. Original English publications of stage I
      NSCLC with adequate sample sizes and adequate SBRT doses were included. A
      multivariate random effects model was used to perform a meta-analysis to compare
      survival between treatments while adjusting for differences in patient
      characteristics. RESULTS: Forty SBRT studies (4850 patients) and 23 surgery
      studies (7071 patients) published in the same period were eligible. The median
      age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66
      years and 37 months for surgery patients, respectively. The mean unadjusted
      overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and
      41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and
      71.7% with limited lung resections. In SBRT studies, overall survival improved
      with increasing proportion of operable patients. After we adjusted for proportion
      of operable patients and age, SBRT and surgery had similar estimated overall and
      disease-free survival. CONCLUSIONS: Patients treated with SBRT differ
      substantially from patients treated with surgery in age and operability. After
      adjustment for these differences, OS and DFS do not differ significantly between
      SBRT and surgery in patients with operable stage I NSCLC. A randomized
      prospective trial is warranted to compare the efficacy of SBRT and surgery.

PMID- 25052563
TI  - Gross motor function is an important predictor of daily physical activity in
      young people with bilateral spastic cerebral palsy.
AB  - AIM: The aim of the study was to describe daily physical activity levels of
      adolescents and young adults with bilateral spastic cerebral palsy (CP) and to
      identify factors that help predict these levels. METHOD: Daily physical activity
      was measured using an accelerometer-based activity monitor in 45 young people
      with bilateral spastic CP (23 males, 22 females; mean age 18y 6mo [SD 2y 5mo]
      range 16y 1mo-20y 11mo); classified as Gross Motor Function Classification System
      (GMFCS) level II or III and with contractures of <20 degrees  at hip and knee.
      Predictor variables included demographic characteristics (age, sex, weight) and
      physical characteristics (gross motor function, lower limb muscle strength, 6min
      walk distance). Data were analyzed using the information-theoretic approach,
      using the Akaike information criterion (AIC) and linear regression. RESULTS:
      Daily activity levels were low compared with published norms. Gross Motor
      Function Measure Dimension-E (GMFM-E; walking, running, and jumping) was the only
      common predictor variable in models that best predicted energy expenditure,
      number of steps, and time spent sitting/lying. GMFM Dimension-D (standing) and
      bilateral reverse leg press strength contributed to the models that predicted
      daily physical activity. INTERPRETATION: Adolescents and young adults with
      bilateral spastic CP and mild to moderate walking disabilities have low levels of
      daily activity. The GMFM-E was an important predictor of daily physical activity.

PMID- 25052561
TI  - Proton beam therapy versus conformal photon radiation therapy for childhood
      craniopharyngioma: multi-institutional analysis of outcomes, cyst dynamics, and
      toxicity.
AB  - PURPOSE: We compared proton beam therapy (PBT) with intensity modulated radiation
      therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst
      dynamics, and toxicity. METHODS AND MATERIALS: We reviewed records from 52
      children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012.
      Endpoints were overall survival (OS), disease control, cyst dynamics, and
      toxicity. RESULTS: At 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo;
      P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free
      survival and 76% for cystic failure-free survival. Neither OS nor disease control
      differed between treatment groups (OS P=.742; nodular failure-free survival
      P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had
      cyst growth (20% requiring intervention); immediately after therapy, 17 patients
      (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs
      19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT;
      P=.353), with intervention required in 40%. Toxicity did not differ between
      groups. On multivariate analysis, cyst growth was related to visual and
      hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as
      salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of
      visual and endocrine (P=.017 and .024, respectively) dysfunction. CONCLUSIONS:
      Survival and disease-control outcomes were equivalent for PBT and IMRT. Cyst
      growth is common, unpredictable, and should be followed during and after therapy,
      because it contributes to late toxicity. Delaying radiation therapy until
      recurrence may result in worse visual and endocrine function.

PMID- 25052564
TI  - Speeding of spherulitic growth rate at the late stage of isothermal
      crystallization due to interfacial diffusion for double-layer semicrystalline
      polymer films.
AB  - In this study a unique phenomenon has been found for isothermal crystallization
      of double-layer semicrystalline polymer films. It is surprisingly found that
      there exists a speeding of poly(l-lactic acid) (PLA) spherulitic growth rate for
      poly(ethylene oxide)/poly(l-lactic acid) (PEO/PLA) double-layer films at the late
      stage of isothermal crystallization, which does not exist for PLA/PEO blend films
      and neat PLA films. The mutual diffusion between PEO and PLA layers plays the key
      factor to bring out the observed speeding of spherulitic growth rate. This type
      of study provides an avenue for understanding the interplay between polymer
      crystallization and interfacial diffusion in multilayer polymer films, which is
      not available when employing the polymer blend films. 

PMID- 25052565
TI  - Facile hydrothermal synthesis of CuFeO2 hexagonal platelets/rings and graphene
      composites as anode materials for lithium ion batteries.
AB  - Delafossite CuFeO2 hexagonal platelets/rings and graphene composites were
      synthesized by a low temperature hydrothermal method. The formation mechanism of
      CuFeO2 hexagonal platelets/rings follows the combined effects of both GO and
      NaOH. The obtained composites as anode materials display a good battery
      performance with high reversible capacity, good rate capability and cyclic
      stability. 

PMID- 25052566
TI  - Botulinum toxin therapy of cervical dystonia: duration of therapeutic effects.
AB  - We sought to explore the therapeutic effect of botulinum toxin (BT) therapy by
      analysing the time between the BT application and the onset of its decrease
      (treatment duration, TD), the inter-injection interval (II), and the excess time
      (ET, ET = II-TD). For this we studied 59 patients (37 females, 22 males, age 52.6
      +/- 10.9 years) with cervical dystonia (CD, Tsui score 9.0 +/- 4.1) and BT
      therapy with Botox((r)) and/or Xeomin((r)) sequentially. Altogether 1,289
      treatment cycles were evaluated. On average 21.8 +/- 14.0 (4-66) treatment cycles
      were recorded for each patient. TD was 11.8 +/- 2.7 weeks (7.8 +/- 1.4 to 21.0 +/
      3.9 weeks), II 15.4 +/- 3.4 weeks (11.3 +/- 1.3 to 27.8 +/- 11.6 weeks) and ET
      3.5 +/- 2.4 weeks (23% of II). TD and II were stable throughout the treatment
      course. In 36% of the patients we found TD <=10 weeks, in 83% TD <=12 weeks. In
      17% of the patients we saw treatment delays due to appointment difficulties, due
      to the patient's attempts to explore TD or his actual CD severity, from fear of
      adverse effects or due to psychiatric comorbidity. 19% of the patients showed
      prolonged treatment effects probably due to CD fluctuations. 0.38% of the
      injection series produced singular unexplained therapy failure (SUTF). Antibody
      induced therapy failure did not occur. TD and II are stable on long-term
      monitoring. SUTF, treatment delays, and CD fluctuations can occur. 23% of the
      time patients are treated suboptimally. Our data suggest to reduce II. If II is
      to be reduced to <=12 weeks, use of low antigenicity BT drugs might be useful.

PMID- 25052567
TI  - Phytoestrogen alpha-zearalanol exerts antiapoptotic effects in differentiated
      pc12 cells via oestrogen receptor alpha.
AB  - Our previous studies have demonstrated that phytoestrogen alpha-zearalanol (alpha
      ZAL) possesses potential benefits in alleviating cell apoptotic death just like
      oestrogen. However, the underlying mechanism is not fully understood. This study
      was designed to test the hypothesis that the neuroprotective effect of alpha-ZAL
      is mediated by oestrogen receptor (ER) as alpha-ZAL owns the benzene ring
      structure may interact with ER. The present results showed a significant increase
      in apoptosis in differentiated PC12 cells after a 24-hr exposure to amyloid beta
      peptide fragment 25-35 (Abeta25-35 ), accompanied by decreasing of bcl-2
      expression and increasing bax expression, whereas a pre-treatment with alpha-ZAL
      ameliorated these changes induced by Abeta25-35 . In addition, the alpha-ZAL
      mediated cytoprotection was abrogated by ERalpha antagonist but not by ERbeta
      antagonist. In summary, these data suggest that alpha-ZAL intervenes against
      Abeta-induced apoptosis via intersecting bcl-2-bax apoptotic pathway in an
      ERalpha-sensitive manner. 

PMID- 25052568
TI  - Application of agriculture-developed demographic analysis for the conservation of
      the Hawaiian alpine wekiu bug.
AB  - Insects that should be considered for conservation attention are often overlooked
      because of a lack of data. The detailed information necessary to assess
      population growth, decline, and maximum range is particularly difficult to
      acquire for rare and cryptic species. Many of these difficulties can be overcome
      with the use of life table analyses and heat energy accumulation models common in
      agriculture. The wekiu bug (Nysius wekiuicola), endemic to the summit of one
      volcanic mountain in Hawaii, is a rare insect living in an environmentally
      sensitive alpine stone desert, where field-based population assessments would be
      inefficient or potentially detrimental to natural and cultural resources. We
      conducted laboratory experiments with the insects by manipulating rearing
      temperatures of laboratory colonies and made detailed observations of habitat
      conditions to develop life tables representing population growth parameters and
      environmental models for wekiu bug phenology and demographic change. Wekiu bugs
      developed at temperatures only found in its environment on sunny days and
      required the thermal buffer found on cinder cones for growth and population
      increase. Wekiu bugs required approximately 3.5 months to complete one
      generation. The bug developed optimally from 26 to 30  degrees C, temperatures
      that are much higher than the air temperature attains in its elevational range.
      The developmental temperature range of the species confirmed a physiological
      reason why the wekiu bug is only found on cinder cones. This physiology
      information can help guide population monitoring and inform habitat restoration
      and conservation. The wekiu bug was a candidate for listing under the U.S.
      Endangered Species Act, and the developmental parameters we quantified were used
      to determine the species would not be listed as endangered or threatened. The use
      of developmental threshold experiments, life table analyses, and degree day
      modeling can directly inform otherwise unobservable habitat needs and demographic
      characteristics of extremely rare insects.

PMID- 25052570
TI  - Renal tight junction proteins are decreased in cisplatin-induced nephrotoxicity
      in rats.
AB  - Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and
      oxidative stress. It is unknown whether renal tight junction (TJ) proteins
      expression and localization are modified in CP-induced nephrotoxicity. OBJECTIVE:
      To study if the expression of the TJ proteins occludin, claudin-2, claudin-5 and
      zonula occludens-1 (ZO-1) is modified in rats with CP-induced nephrotoxicity.
      MATERIALS AND METHODS: Male Wistar rats (n = 5/group) were injected with saline
      solution (V group), and the other group (CP group) was injected with a single
      dose of saline solution and CP (7.5 mg/kg i.p.). Rats were sacrificed 72 h after
      CP injection and blood, and 24-h urine samples were collected. Several plasma and
      urinary injury biomarkers as well as renal histopathology lesions, oxidative and
      nitrosative stress markers were evaluated, and protein levels of ocludin, claudin
      2, claudin-5, ZO-1 were measured by Western blot. Statistically significant
      changes noted with different p < 0.05 versus V. RESULTS: Nephrotoxicity was
      evident by histological alterations, glycosuria, decrease in creatinine
      clearance, increase in fractional excretion of sodium, serum creatinine and
      kidney injury molecule-1. These changes were associated with
      oxidative/nitrosative stress (increased renal abundance of 3-nitrotyrosine and
      protein kinase Cbeta2 and decreased renal expression of nuclear factor-erythroid
      2-related factor 2) and decreased activity of antioxidant enzymes. Finally, it
      was found that CP-induced renal damage was associated with decreased renal
      expression of occludin and claudin-2. DISCUSSION AND CONCLUSION: CP altered the
      TJ proteins expression and localization in the proximal tubule that was
      associated with oxidative/nitrosative stress.

PMID- 25052571
TI  - The role of adipokines in periodontal infection and healing.
AB  - Periodontitis is a chronic inflammatory disease of the periodontium, which is
      caused by pathogenic bacteria in combination with other risk factors. The
      bacteria induce an immunoinflammatory host response, which can lead to
      irreversible matrix degradation and bone resorption. Periodontitis can be
      successfully treated. To achieve regenerative periodontal healing, bioactive
      molecules, such as enamel matrix derivative (EMD), are applied during periodontal
      surgery. Recently, it has been shown that obesity is associated with
      periodontitis and compromised healing after periodontal therapy. The mechanisms
      underlying these associations are not well understood so far, but adipokines may
      be a pathomechanistic link. Adipokines are bioactive molecules that are secreted
      by the adipose tissue, and that regulate insulin sensitivity and energy
      expenditure, but also inflammatory and healing processes. It has also been
      demonstrated that visfatin and leptin increase the synthesis of proinflammatory
      and proteolytic molecules, whereas adiponectin downregulates the production of
      such mediators in periodontal cells. In addition, visfatin and leptin counteract
      the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on
      periodontal cells. Since visfatin and leptin levels are increased and adiponectin
      levels are reduced in obesity, these adipokines could be a pathomechanistic link
      whereby obesity and obesity-related diseases enhance the risk for periodontitis
      and compromised periodontal healing. Recent studies have also revealed that
      adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal
      cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may
      also represent a mechanism whereby periodontal infections can impact on systemic
      diseases.

PMID- 25052572
TI  - Internal mandibular distraction to relieve airway obstruction in children with
      severe micrognathia.
AB  - Congenital craniofacial malformations such as Pierre Robin sequence or Treacher
      Collins syndrome are associated with mandibular micrognathia, resulting in
      obstructive sleep apnea (OSA) due to a decreased pharyngeal airway; in severe
      cases this leads to tracheostomy dependence. We present a series of 18 patients
      in whom we performed mandibular lengthening using internal distraction devices to
      relieve airway obstruction. Seven were tracheostomy-dependent and 11 were
      respiratory distressed without tracheostomy. The mandible was distracted at a
      rate of 1mm per day. Following 3 months of consolidation for bony maturation, the
      distraction devices were removed. Results demonstrated forward mandibular
      elongation of a mean 22mm (range 20-25mm) and an increase in SNB angle and in
      pharyngeal airway. All patients with tracheostomies were decannulated, and there
      was an improved airway with resolution of signs and symptoms of OSA and
      elimination of oxygen requirement in all patients. We conclude that mandibular
      distraction using internal devices is a useful and comfortable method for younger
      children to expand the mandible forward and increase the pharyngeal airway.

PMID- 25052573
TI  - Assessing change in quality of life using the Oral Health Impact Profile (OHIP)
      in patients with different dentofacial deformities undergoing orthognathic
      surgery: a before and after comparison.
AB  - Dentofacial deformities and their treatment have physical and psychological
      repercussions on quality of life (QOL). Seventy-four patients were evaluated
      preoperatively (T0) and at 4-6 months postoperatively (T1). Oral health-related
      QOL was assessed using the short form of the Oral Health Impact Profile (OHIP
      14). There was a statistically significant reduction in the average overall OHIP
      14 score between T0 (13.23+/-6.45) and T1 (3.26+/-4.19). In addition, there were
      significant decreases in all seven OHIP-14 domains. Class III patients benefited
      in all domains evaluated, while a significant improvement was seen only in the
      psychological disability domain for class I patients. Class II patients showed a
      significant benefit in all domains except the domain of functional limitation.
      With regard to the total sample (n=74) and class III patients (n=58),
      correlations between domains were identified for all domains. The same
      correlation was not identified for class I (n=5) and II (n=11) patients. The
      entire sample and class III patients showed significant improvements in OHIP-14
      scores for all degrees of postoperative sensory disturbance in the upper and
      lower lips, except for patients with degree 5 (extreme) disturbance of the upper
      lip. Orthognathic surgical treatment had a positive impact on oral health-related
      QOL in the patients evaluated. 

PMID- 25052574
TI  - PRO: confronting resistance to rule-based medicine is essential to improving
      outcomes.
AB  - The past 20 years have seen two great changes in the practice of medicine: the
      widespread adoption of evidence-based medicine, and the increasing challenge of
      managing complex multimorbid patients. Both these developments have resulted in
      clinical rules and protocols becoming ever more abundant and increasingly
      critical to delivering safe and effective patient care. These evidence-based
      clinical rules perform at least as well as expert opinion, and the increasing
      volume and quality of available clinical data suggests their performance could
      continue to improve. This article considers why clinicians deviate from effective
      rules, highlighting key issues such as the persisting culture of heroism,
      institutional inertia, deference to authority and personal heuristics. We argue
      that better rules can be created, and that clinical improvements will follow if
      there is a 'common knowledge' of these rules. Furthermore, we argue that there is
      a ceiling to the effectiveness of any rule, even one as simple as ensuring hand
      hygiene, unless individuals are held accountable for transgressions.

PMID- 25052575
TI  - Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with
      misalignment of pulmonary veins.
AB  - Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a
      lethal neonatal lung disease characterised by severe pulmonary hypertension,
      abnormal vasculature and intractable hypoxaemia. Mechanisms linking abnormal lung
      vasculature with severe hypoxaemia in ACD/MPV are unknown. We investigated
      whether bronchopulmonary anastomoses form right-to-left shunt pathways in
      ACD/MVP. We studied 2 infants who died of ACD/MPV postmortem with direct
      injections of coloured ink into the pulmonary artery, bronchial artery and
      pulmonary veins. Extensive histological evaluations included serial sectioning,
      immunostaining and 3-dimensional reconstruction demonstrated striking
      intrapulmonary vascular pathways linking the systemic and pulmonary circulations
      that bypass the alveolar capillary bed. These data support the role of prominent
      right-to-left intrapulmonary vascular shunt pathways in the pathophysiology of
      ACD/MPV. 

PMID- 25052576
TI  - The child is father of the man: the importance of early life influences on lung
      development.

PMID- 25052577
TI  - Letter to the editor in reply to 'pulmonary vascular volumes and airways
      obstruction in SCD patients'.

PMID- 25052578
TI  - Intermittent hemodialysis treatment in cefepime-induced neurotoxicity: case
      report, pharmacokinetic modeling, and review of the literature.
AB  - Cefepime is a broad-spectrum cephalosporin indicated for in-hospital treatment of
      severe infections. Acute neurotoxicity, an increasingly recognized adverse effect
      of this drug in an overdose, predominantly affects patients with reduced renal
      function. Although dialytic approaches have been advocated to treat this
      condition, their role in this indication remains unclear. We report the case of
      an 88-year-old female patient with impaired renal function who developed life
      threatening neurologic symptoms during cefepime therapy. She was treated with two
      intermittent 3-hour high-flux, high-efficiency hemodialysis sessions. Serial pre
      , post-, and peridialytic (pre- and postfilter) serum cefepime concentrations
      were measured. Pharmacokinetic modeling showed that this dialytic strategy
      allowed for serum cefepime concentrations to return to the estimated nontoxic
      range 15 hours earlier than would have been the case without an intervention. The
      patient made a full clinical recovery over the next 48 hours. We conclude that at
      least 1 session of intermittent hemodialysis may shorten the time to return to
      the nontoxic range in severe clinically patent intoxication. It should be
      considered early in its clinical course pending chemical confirmation, even in
      frail elderly patients. Careful dosage adjustment and a high index of suspicion
      are essential in this population. 

PMID- 25052579
TI  - Commentary: Attachment is a biological concept--a reflection on Fearon et al.
      (2014).
AB  - This article is a commentary on Fearon et al. (2014, Genetic and environmental
      influences on adolescent attachment) published in this issue. 

PMID- 25052580
TI  - Avian influenza viruses inhibit the major cellular signalling integrator c-Abl.
AB  - The non-structural protein 1 (NS1) of influenza A viruses (IAV) encodes several
      src homology (SH) binding motifs (bm) (one SH2bm, up to two SH3bm), which mediate
      interactions with host cell proteins. In contrast to NS1 of human IAV, NS1 of
      avian strains possess the second SH3bm (SH3(II)bm) consensus sequence. Since our
      former studies demonstrated an NS1-CRK interaction, mediated by this motif, here,
      we addressed the regulatory properties of this SH3bm for cellular signalling.
      Initially, we observed a reduced basal CRK phosphorylation upon infection with
      avian IAV harbouring an NS1 with an SH3(II)bm in contrast to human IAV. Reduced
      activity of the tyrosine kinase c-Abl was identified to be responsible for
      reduced CRK phosphorylation. Further, binding of NS1 to c-Abl was determined, and
      mutational manipulation of the SH3(II)bm illustrated the necessity of this motif
      for c-Abl inhibition. Interestingly, Abl kinase inhibition resulted in impaired
      avian IAV propagation and pathogenicity and mutational analysis linked the
      pronounced inhibition of c-Abl to cytopathogenic cell alterations upon avian IAV
      infections. Taken together, NS1 proteins of avian IAV interfere with the kinase
      activity of c-Abl, a major cellular signalling integrator that controls multiple
      signalling processes and cell fate regulations apparently including IAV
      infections.

PMID- 25052581
TI  - Cardiac biomarkers for infarct diagnosis and early exclusion of acute coronary
      syndrome.
AB  - The acute coronary syndrome (ACS) represents a diagnostic challenge: on the one
      hand patients need to be quickly identified to initiate treatment and on the
      other hand early exclusion of patients without ACS is important to relieve
      patient stress as well as overcrowded emergency departments. A growing number of
      biomarkers are becoming available to aid physicians with this task. This review
      gives an overview of the current research concerning early exclusion with an
      emphasis on the clinically most important biomarker: cardiac troponin. 

PMID- 25052582
TI  - A comparative review of nurse turnover rates and costs across countries.
AB  - AIMS: To compare nurse turnover rates and costs from four studies in four
      countries (US, Canada, Australia, New Zealand) that have used the same costing
      methodology; the original Nursing Turnover Cost Calculation Methodology.
      BACKGROUND: Measuring and comparing the costs and rates of turnover is difficult
      because of differences in definitions and methodologies. DESIGN: Comparative
      review. DATA SOURCES: Searches were carried out within CINAHL, Business Source
      Complete and Medline for studies that used the original Nursing Turnover Cost
      Calculation Methodology and reported on both costs and rates of nurse turnover,
      published from 2014 and prior. METHODS: A comparative review of turnover data was
      conducted using four studies that employed the original Nursing Turnover Cost
      Calculation Methodology. Costing data items were converted to percentages, while
      total turnover costs were converted to US 2014 dollars and adjusted according to
      inflation rates, to permit cross-country comparisons. RESULTS: Despite using the
      same methodology, Australia reported significantly higher turnover costs
      ($48,790) due to higher termination (~50% of indirect costs) and temporary
      replacement costs (~90% of direct costs). Costs were almost 50% lower in the US
      ($20,561), Canada ($26,652) and New Zealand ($23,711). Turnover rates also varied
      significantly across countries with the highest rate reported in New Zealand
      (44.3%) followed by the US (26.8%), Canada (19.9%) and Australia (15.1%).
      CONCLUSION: A significant proportion of turnover costs are attributed to
      temporary replacement, highlighting the importance of nurse retention. The
      authors suggest a minimum dataset is also required to eliminate potential
      variability across countries, states, hospitals and departments.

PMID- 25052583
TI  - Myeloid Kruppel-like factor 2 deficiency exacerbates neurological dysfunction and
      neuroinflammation in a murine model of multiple sclerosis.
AB  - Cells of the innate immune system are important mediators of multiple sclerosis
      (MS). We have previously identified Kruppel-like factor 2 (KLF2) as a critical
      negative regulator of myeloid activation in the setting of bacterial infection
      and sepsis, but the role of myeloid KLF2 in MS has not been investigated. In this
      study, myeloid KLF2 deficient mice exhibited more severe neurological dysfunction
      and increased spinal cord demyelination and neuroinflammation in experimental
      autoimmune encephalomyelitis. This study represents the first description of a
      significant role of myeloid KLF2 in neuroinflammation, identifying KLF2 as a
      potential target for further investigation in patients with MS. 

PMID- 25052584
TI  - Day/night changes of thymus-deriving natural regulatory T cell development and
      function.
AB  - Activity of the immune system shows day/night rhythmicity. Changes in the
      migration and biological activities of immune cells are strongly regulated by the
      HPA axis. Another mechanism governing the level of the immune response is based
      on the suppressive activity of natural regulatory T cells CD4+CD25+Foxp3+
      (nTregs) which play a crucial role in the maintenance of self-tolerance and
      immune homeostasis. The aim of our study was to answer the question: are nTregs
      changing their development and suppressive activity according to day/night cycle?
      We demonstrated the effect of day time on nTreg distribution in the thymus and
      their suppressive potential to inhibit the proliferation of activated responder T
      cells. 

PMID- 25052586
TI  - Center of pressure trajectory during gait: a comparison of four foot positions.
AB  - Knowledge of the center of pressure (COP) trajectory during stance can elucidate
      possible foot pathology, provide comparative effectiveness of foot orthotics, and
      allow for appropriate calculation of balance control and joint kinetics during
      gait. Therefore, the goal of this study was to investigate the COP movement when
      walking at self-selected speeds with plantigrade, equinus, inverted, and everted
      foot positions. A total of 13 healthy subjects were asked to walk barefoot across
      an 8-m walkway with embedded force plates. The COP was computed for each stance
      limb using the ground reaction forces and moments collected from three force
      plates. Results demonstrated that the COP excursion was 83% of the foot length
      and 27% of the foot width in the anterior-posterior and medial lateral directions
      for plantigrade walking, respectively. Regression equations explained 94% and 44%
      of the anterior-posterior and medial-lateral COP variability during plantigrade
      walking, respectively. While the range of motion and COP velocity were similar
      for inverted and everted walking, the COP remained on the lateral and medial
      aspects of the foot for these two walking conditions, respectively. A reduced
      anterior-posterior COP range of motion and velocity were demonstrated during
      equinus walking. Ankle joint motion in the frontal and sagittal planes supported
      this COP movement, with increased inversion and plantar flexion demonstrated
      during inverted and equinus conditions, respectively. Results from this study
      demonstrated the COP kinematics during simulated pathological gait conditions,
      with the COP trajectory providing an additional tool for the evaluation of
      patients with pathology. 

PMID- 25052585
TI  - Differentially expressed microRNA cohorts in seed development may contribute to
      poor grain filling of inferior spikelets in rice.
AB  - BACKGROUND: The inferior spikelets are defined to be those at portions where the
      grains receive less photosynthetic products during the seed development. The
      typical inferior spikelets are physically located on the proximal secondary
      branches in a rice panicle and traditionally characterized by a later flowering
      time and a slower grain-filling rate, compared to those so-called superior
      spikelets. Grains produced on the inferior spikelets are consequently under
      developed and lighter in weight than those formed on the superior spikelets.
      MicroRNAs (miRNAs) are recognized as key players in regulating plant development
      through post-transcriptional gene regulations. We previously presented the
      evidence that miRNAs may influence grain-filling rate and played a role in
      determining the grain weight and yield in rice. RESULTS: In this study, further
      analyses of the expressed small RNAs in superior and inferior spikelets were
      conducted at five distinct developmental stages of grain development. Totally,
      457 known miRNAs and 13 novel miRNAs were analyzed, showing a differential
      expression of 141 known miRNAs between superior and inferior spikelets with
      higher expression levels of most miRNAs associated with the superior than the
      inferior spikelets during the early stage of grain filling. Genes targeted by
      those differentially expressed miRNAs (i.e. miR156, miR164, miR167, miR397,
      miR1861, and miR1867) were recognized to play roles in multiple developmental and
      signaling pathways related to plant hormone homeostasis and starch accumulation.
      CONCLUSIONS: Our data established a complicated link between miRNA dynamics and
      the traditional role of hormones in grain filling and development, providing new
      insights into the widely accepted concepts of the so-called superior and inferior
      spikelets in rice production.

PMID- 25052588
TI  - Thermoelectric performance of Ni compensated cerium and neodymium double filled p
      type skutterudites.
AB  - We have synthesized Ni compensated Ce and Nd double filled p-type skutterudites
      CexNdxFe3.7Ni0.3Sb12 with x = 0.35, 0.40, 0.45, and 0.5 by a melting-quenching
      annealing method. The samples were made by directly hot pressing the hand ground
      powder at 650  degrees C for 5 minutes at a pressure of about 80 MPa. Since Ni
      has two more electrons than Fe, a lower power factor and a stronger bipolar
      effect in thermal conductivity are expected at higher temperature. In the
      experiments, we have demonstrated that by suitably tuning the Fe-Ni ratio and
      filler concentration, we can achieve both a higher power factor (~35 MUW cm(-1)
      K(-2) at 535  degrees C) and a lower thermal conductivity (~2.1 W m(-1) K(-1) at
      room temperature and ~2.7 W m(-1) K(-1) at 535  degrees C) in
      Ce0.4Nd0.4Fe3.7Ni0.3Sb12. A peak thermoelectric figure-of-merit of ~1.1 at 475 
      degrees C is achieved in Ce0.4Nd0.4Fe3.7Ni0.3Sb12. 

PMID- 25052587
TI  - Weight and body mass index in relation to irradiated volume and to overall
      survival in patients with oropharyngeal cancer: a retrospective cohort study.
AB  - BACKGROUND: Weight loss is a common problem in patients with Squamous Cell
      Carcinoma of the Head and Neck (SCCHN) treated with radiotherapy (RT). The aims
      of the present study were to determine if treated volume (TV), as a measure of
      the radiation dose burden, can predict weight loss in patients with oropharyngeal
      cancer and to analyze weight loss and body mass index (BMI) in the same patient
      group in relation to 5-year overall survival. METHODS: The ARTSCAN trial is a
      prospective, randomized, multicenter trial in patients with SCCHN. Nutritional
      data from the ARTSCAN trial were analyzed retrospectively using univariate and
      multivariate statistical methods based on information on percentage weight loss
      from the start of RT up to five months after the termination of RT (study cohort
      1, n = 232) and information on patients' BMI at the start of RT (study cohort 2,
      n = 203). TV was defined as the volume of the patient receiving at least 95% of
      the prescribed dose. TV64.6 Gy encompasses macroscopic tumor and TV43.7 Gy
      elective lymph nodes of the neck. RESULTS: TV64.6 Gy and TV43.7 Gy were both
      significantly correlated with higher weight loss up to five months after the
      termination of RT in study cohort 1 (p < 0.001 for both). BMI at the start of RT
      was shown to be a prognostic factor for 5-year overall survival in study cohort 2
      but weight loss was not. The hazard ratios and 95% confidence intervals were 3.78
      (1.46-9.75) and 2.57 (1.43-4.62) in patients with underweight and normal weight,
      respectively. CONCLUSIONS: TV can predict weight loss during RT in patients with
      oropharyngeal cancer regardless of clinical stage. A high BMI (>25 kg/m2) at the
      start of RT is positively associated with survival in patients with oropharyngeal
      cancer.

PMID- 25052589
TI  - An audit of the frequency of proton pump inhibitor (PPI) prescription in
      rheumatoid arthritis (RA) patients taking non-steroidal anti-inflammatory drugs
      (NSAIDs).

PMID- 25052590
TI  - Evaluation of the Candida albicans removal and mechanical properties of denture
      acrylics cleaned by a low-cost powered toothbrush.
AB  - PURPOSE: To investigate the effects of using a low-cost powered toothbrush for
      cleaning on dental prostheses made of heat polymerized poly(methyl methacrylate),
      PMMA. METHODS: Heat cured PMMA specimens beam with the dimensions of 45.0 mm*6.5
      mm*4.5mm were fabricated. The specimens were kept in water storage at 37  degrees
      C constant temperature for 0, 1, 7, 15, 30 and 60 days and randomly assigned for
      testing or control. Test specimens underwent brushing by using a powered
      toothbrush at an applied force of 2.00 N for 22 min with water as medium. Surface
      roughness measurement (Ra), flexural strength and efficacy of brushing to remove
      coated Candida albicans biofilm were investigated. RESULTS: The results of the
      mean surface roughness value and the flexural strength were analysed by using two
      way ANOVA and Tukey post hoc test at 5% significance level. In general, the
      specimens showed no significant changes in flexural strength after brushing.
      However, the flexural strength and the surface roughness value were significantly
      lower in specimens group after 7 days in water storage compared to the control.
      SEM micrographs of post-brushed specimens revealed satisfactory removal of C.
      albicans biofilm. CONCLUSION: A low-cost powered toothbrush together with a
      liquid medium successfully removed C. albicans biofilm on dental acrylic PMMA
      based prostheses, without compromising the mechanical properties.

PMID- 25052591
TI  - Regulating the diverse outcomes of interferon's interference.
AB  - Regulatory T cells are crucial for preventing autoimmunity, but how their
      function is restrained to allow optimal effector T cells responses in appropriate
      contexts is unclear. In a recent paper in the Journal of Experimental Medicine,
      Campbell and colleagues demonstrate that virus-induced type I interferon acts
      directly on Treg cells to allow for functional antiviral T cell responses. 

PMID- 25052592
TI  - A review of selected chemical additives in cosmetic products.
AB  - The addition of chemical additives to consumer cosmetic products is a common
      practice to increase cosmetic effectiveness, maintain cosmetic efficacy, and
      produce a longer-lasting, more viable product. Recently, manufacturers have come
      under attack for the addition of chemicals including dioxane, formaldehyde,
      lead/lead acetate, parabens, and phthalate, as these additives may prove harmful
      to consumer health. Although reports show that these products may indeed
      adversely affect human health, these studies are conducted using levels of the
      aforementioned chemicals at much higher levels of exposure than those found in
      cosmetic products. When cosmeceuticals are used as per manufacturer's
      instructions, it is estimated that the levels of harmful additives found in these
      products are considerably lower than reported toxic concentrations.

PMID- 25052595
TI  - [Clinical investigation of reduced-dose voriconazole on primary prevention in
      invasive fungal disease after allogeneic hematopoietic stem cell
      transplantation].
AB  - OBJECTIVE: To investigate the efficacy and tolerability of intravenous
      voriconazole on primary prevention in invasive fungal disease (IFD) after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: At the
      time of conditioning regimen, patients without IFD was intravenously administered
      with voriconazole at a dose of 100 mg two times per day until neutrophils greater
      than 0.5*109/L. Patients treated with oral fluconazole, 200 mg per day, were
      control group. The incidence and risk factors of IFD and side effects of
      medicines were evaluated. RESULTS: Of the total 227 patients, 33 (14.54%) had IFD
      within 3 months after allo-HSCT. There was significant difference on overall
      survival between patients with or without IFD by Kaplan-Meier survival curve
      (P=0.029). Of the 83 cases with intravenous voriconazole, 7 cases occurred IFD
      (8.43%). In contrast, the incidence of IFD in control group was 18.06% (26 out of
      144). There was remarkable difference between the two groups (P=0.048). But there
      was no significant difference on risk factors of IFD between the two groups. In
      addition, the incidence of liver function abnormalities between the two groups
      was no difference. The ratio of auditory hallucination and visual impairment
      induced by voriconazole was not high. CONCLUSION: Intravenous voriconazole on
      primary prevention for IFD after allo-HSCT is much better than oral fluconazole
      with well tolerability and satisfactory efficacy.

PMID- 25052594
TI  - Hepatitis C virus NS3 protease genotyping and drug concentration determination
      during triple therapy with telaprevir or boceprevir for chronic infection with
      genotype 1 viruses, southeastern France.
AB  - Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease
      inhibitors (PIs), considerably increase rates of sustained virologic response in
      association with pegylated interferon and ribavirin in chronic HCV genotype 1
      infections. The 30 first patients treated by telaprevir or boceprevir including
      anti-HCV therapies since 2011 in Marseille University hospitals, France, were
      monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir
      were determined on sequential blood samples. HCV NS3 protease gene population
      sequencing was performed at baseline of treatment and in case of treatment
      failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir
      and the other 15 patients (including 4 co-infected with HIV) received boceprevir.
      At baseline, HCV NS3 protease from six patients harbored amino acid substitutions
      associated with PI-resistance. Treatment failure occurred at week 12 for 7
      patients. Amino acid substitutions associated with PI-resistance were observed in
      six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were
      found from four patients. Median (interquartile range) plasma concentrations were
      3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir.
      For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270
      4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug
      concentration monitoring revealed undetectable concentrations for two patients at
      week 4, and probable non-adherence to therapy for another patient. These findings
      indicate that routine HCV NS3 protease sequencing and plasma PI concentration
      monitoring might be helpful to characterize cases of therapy failure, at a cost
      dramatically low compared to that of anti-HCV therapy.

PMID- 25052596
TI  - [Reversible pulmonary arterial hypertension related to dasatinib in the treatment
      for chronic myelogenous leukemia: a case report and literature review].
AB  - OBJECTIVE: To study the clinical features and prognosis of pulmonary arterial
      hypertension associated with dasatinib. METHODS: To present a case of pulmonary
      arterial hypertension (PAH) associated with long-term exposure to dasatinib and
      review the related literatures. RESULTS: A 23-year-old female with chronic
      myelogenous leukemia was treated with dasatinib at a dosage of 140 mg/d after
      failure of imatinib treatment and achieved complete cytogenetic response. The
      patient was presented with exertional dyspnea after 35 months of administration
      with dasatinib. The electrocardiogram showed right ventricular hypertrophy and
      right axis deviation; transthoracic Doppler echocardiography documented a
      reduction in diameters of left heart chambers with normal systolic left
      ventricular function, right heart chambers and pulmonary trunk dilatation, an
      estimated pulmonary arterial pressure of 114 mmHg; Computed tomography showed
      thickened pulmonary artery. PAH related to dasatinib was diagnosed and dasatinib
      was permanently discontinued. The symptom of dyspnea disappeared quickly after
      withdrawal of dasatinib. The heart structure and pulmonary arterial pressure
      completely recovered after 7 months of dasatinib discontinuation. CONCLUSION: PAH
      is a rare adverse effect of dasatinib treatment. Echocardiograhpy, as a non
      invasive screening test for PAH, should be performed before starting dasatinib
      treatment and repeated during the administration with dasatinib. Dasatinib should
      be withdrawn permanently in patients with PAH.

PMID- 25052597
TI  - [Effect of intermediate-dose cytarabine on mobilization of peripheral blood
      hematopoietic stem cell in acute myeloid leukemia].
AB  - OBJECTIVE: To explore the impact of courses of intermediate-dose cytarabine (ID
      Ara-C) chemotherapy on the efficiency of hematopoietic stem cell mobilization in
      acute myeloid leukemia (AML) patients with autologous hematopoietic stem cell
      transplantation (auto-HSCT). METHODS: 90 patients with de novo AML undergoing
      auto-HSCT between August 1999 and November 2012 were enrolled. All patients
      received the mobilization regimen of cytarabine and etoposide chemotherapy in
      combination with recombinant human granulocyte-colony stimulating factor (rhG
      CSF). Stem cell apheresis was scheduled when blood leukocyte count recovered
      greater than 4.0 * 109/L or the proportion of CD34+ cells greater than 1% in
      peripheral blood. The impact of ID-Ara-C courses on the mobilization efficiency
      was analyzed retrospectively. RESULTS: According to the ID-Ara-C courses,
      patients were divided into group A (<2 courses), B (2 courses), and C (>2
      courses). The median doses of CD34+ cells (*106/kg) in three groups were 4.7,
      2.7, 2.3, respectively (P=0.003). Of the available 87 patients who could be
      evaluated, 61 (70.1%) cases had CD34+ cells greater than 2.0 * 106/kg, and 26
      (29.9%) cases less than 2.0 * 106/kg. Of the 26 patients without satisfactory
      mobilization efficiency, 7 (15.2%) were in group A, 10 (47.6%) in group B, and 9
      (45.0%) in group C (chi2=10.05, P=0.007). In addition, patients with satisfactory
      mobilization efficiency (CD34+ cells >= 2.0*106/kg) in groups C needed more times
      of collection, more volume of blood processed, and even high-dose and longer
      course of rhG-CSF (P<0.05). In univariate analysis. The ID-Ara-C courses and the
      cumulative dose were significant correlate with mobilization efficiency. In
      multivariate analysis, the ID-Ara-C courses was an independent correlation factor
      for mobilization efficiency (odd ratio=0.623, 95% confidence interval=0.418
      0.926, P=0.019). The sex, age, cytogenetic risk, the standard chemotherapy
      courses did not correlate with mobilization efficiency. CONCLUSION: The number of
      ID-Ara-C courses was independent factor for the mobilization efficiency and
      should be taken seriously in AML patients with auto-HSCT.

PMID- 25052598
TI  - [Chronic lymphocytic leukemia with central nervous system invasion: one case
      report and literature review].
AB  - OBJECTIVE: To investigate clinical features, diagnosis, therapy, and prognosis in
      a case of chronic lymphocytic leukemia (CLL) with central nervous system (CNS)
      invasion. METHODS: The cellular morphology of bone marrow, cytology and flow
      cytometry of cells in CSF, and radiographic manifestations were detected in a
      patient diagnosed as CLL with CNS invasion. The clinical features, pathogenesis,
      diagnosis,therapy, and prognosis of CLL with CNS invasion were reviewed by
      literatures. RESULTS: A clonal population of B lymphocytes with typical
      characteristics of immunophenotype was identified in the patient. After treated
      with intrathecal chemotherapy, the patient returned to normal cells count of
      cerebrospinal fluid and normal neurologic status. Previous studies also have
      demonstrated the efficacy of intrathecal chemotherapy. CONCLUSION: CNS invasion
      is a rare complication of CLL. Early detection and treatment may result in better
      outcomes.

PMID- 25052599
TI  - [Abnormal WT1 gene expression in paroxysmal nocturnal hemoglobinuria].
AB  - OBJECTIVE: To explore the pathogenesis of abnormal WT1 expression in paroxysmal
      nocturnal hemoglobinuria (PNH). METHODS: The expression of WT1 mRNA in CD59- and
      CD59+ bone marrow mononuclear cells (BMMNC) were measured by semi-quantitative
      reverse transcription PCR. After WT1 gene silence by RNA interference (RNAi)
      technology, biological characteristics of BMMNC were investigated by flow
      cytometry. RESULTS: The relative expression of WT1 mRNA in PNH CD59- BMMNC (1.06
      +/- 0.12) was significantly higher than that in PNH CD59+ BMMNC (0.90 +/- 0.12)
      and normal BMMNC (0.86 +/- 0.05, P<0.05), but there was no significant difference
      between PNH CD59+ BMMNC and normal BMMNC (P>0.05). WT1 mRNA expression in PNH was
      positively correlated with the proportion of CD59- cells (r2=0.490, P=0.016), but
      had no relationship with the proportion of CD59+ cells. After WT1 gene silence by
      siRNA in PNH CD59- BMMNC, WT1 mRNA expression was decreased. The proportions of
      G0/G1 phase in PNH CD59- cell blank control group and siRNA-scr transfected group
      were (92.73 +/- 3.71)% and (93.06 +/- 4.14)%, and the proportions of S phase were
      (6.99 +/- 3.61)% and (6.73 +/- 4.08)%, respectively. The proportions of G0/G1 and
      S phase in siRNA-WT1 transfected group was (94.46 +/- 3.71)% and (5.40 +/-
      3.55)%, respectively. There were significant differences in the proportions of
      G0/G1 phase and S phase among the controls, siRNA-WT1 transfected group and siRNA
      scr transfected group (P<0.05). The rate of apoptosis in siRNA-WT1 transfected
      group [(35.91 +/- 22.36)%] was significantly higher than those in controls
      [(26.12 +/- 17.10)%] and siRNA-scr transfected group [(27.39 +/- 18.99)%]
      (P<0.05). CONCLUSION: siRNA-WT1 could effectively suppress the WT1 gene
      expression of CD59- clone in PNH patients, inhibit its proliferation, and promote
      its apoptosis. WT1 gene expression might contribute to PNH clone proliferation.

PMID- 25052600
TI  - [A case of B-lymphoma cell leukemia with Auer rods in peripheral blood].

PMID- 25052601
TI  - [Analysis of a pyruvate kinase deficiency consanguineous pedigree caused by
      Ile314Thr homozygous mutation].
AB  - OBJECTIVE: To screen potential mutation and explore the underlying mechanism for
      a consanguineous pedigree featuring pyruvate kinase (PK) deficiency. METHODS: The
      red blood cell pyruvate kinase activities of all family members were detected.
      All the exons and intron-exon boundaries of the PKLR gene for the proband were
      amplified and analyzed by direct sequencing. Restriction endonuclease enzymes
      were used to identify the presence of mutations of all family members. RESULTS:
      The pyruvate kinase activities were 5.89 U/g Hb in the proband, 3.45, 6.54, 8.87,
      7.89, 9.32 U/g Hb in his younger sister, father, mother, grandmother and elder
      aunt, respectively. The homozygous missense mutation of T>C transition at
      position 941 in exon 7 of PKLR gene resulted to a Ile314Thr substitution in the
      proband, and mutant alleles were identified at the level of RNA transcript by
      cDNA sequence analysis. His younger sister was also homozygous for Ile314Thr.
      Heterozygosity for Ile314Thr was confirmed in his grandmother, parents and elder
      aunt. CONCLUSION: Ile314Thr homozygous missense mutation in exon 7 of PKLR is the
      molecular mechanism of pyruvate kinase deficiency in this family.

PMID- 25052602
TI  - [Telomere length of peripheral lymphocytes in patients with immuno-related
      pancytopenia].
AB  - OBJECTIVE: To investigate the changes of relative telomere length (RTL) of
      peripheral blood (PB) CD3+, CD3+CD4+, CD3+CD8+T lymphocytes, CD19+B lymphocytes
      and bone marrow (BM) CD34+ cells and its association with disease severity in
      untreated patients with immuno-related pancytopenia (IRP). METHODS: The PB CD3+ ,
      CD3+ CD4+ , CD3+ CD8+ T lymphocytes, CD19+ B lymphocytes, and BM CD34+ cells were
      purified by magnetic activated cell sorting (MACS), and RTL were measured with
      flow-fluorescence in situ hybridization (FLOW-FISH). RESULTS: The RTL of CD3+,
      CD3+CD4+ , and CD3+CD8+T lymphocytes in untreated IRP patients were (27.754 +/-
      16.323)%, (7.526 +/- 3.745)% and (25.854 +/- 14.789)%, respectivly, which were
      significantly shorter than those in healthy-controls (54.555 +/- 19.782)%,
      (12.096 +/- 2.805)%, and (38.367 +/- 4.626)% (P<0.05). The RTL of CD19+
      lymphocytes in untreated IRP patients was (22.136 +/- 16.142)%, which was
      significantly shorter than that in healthy controls (42.846 +/- 16.353)%
      (P<0.01). There was no significant difference of BM CD34+ cells RTL between the
      untreated IRP patients (22.528 +/- 21.601)% and the healthy controls (23.936 +/-
      19.822)% (P>0.05). There were significantly positive correlations between the RTL
      of B lymphocytes and the count of white blood cell (r=0.706, P=0.015). There were
      negative correlations between RTL of B lymphocytes and the clinical symptoms (r=
      0.613, P=0.045) and positive correlations with therapeutic effect (r=0.775,
      P=0.005). CONCLUSION: The shorter RTL of CD3+, CD3+CD4+, CD3+CD8+, CD19+
      lymphocytes, and the normal RTL of BM CD34+ cells in untreated IRP patients were
      identified, which might imply that IRP is a type of acquired autoimmune diseases.

PMID- 25052603
TI  - [Chronic natural killer cell lymphocytosis: eight cases report and literature
      review].
AB  - OBJECTIVE: To identify the characteristics of chronic natural killer cell
      lymphocytosis (CNKL). METHODS: The clinical data of eight cases defined by the
      World Health Organization classification was retrospectively analyzed and related
      literatures were reviewed. RESULTS: Half of the 8 patients were asymptomatic.
      Among them, the most common abnormalities were leukocytosis with the median of
      11.8(4.5-20.0)*109/L and high proportion of lymphocytes [0.78(0.51-0.89)], while
      anemia and thrombocytopenia only in 1 patient respectively. The absolute CD3
      CD16+ NK cell count with the median of 5.7(2.4-9.6)*109/L increased in peripheral
      blood. By the end of follow-up, except one case was lost, the other seven
      patients were in stable condition,including four cases without any medications
      and three patients receiving chlorambucil or glucocorticoid. CONCLUSION: As an
      indolent chronic lymphoproliferative disease, CNKL was presented with mild
      clinical symptoms and increased number of CD3-CD16+ NK cells in peripheral blood.
      Patients with symptoms could be treated with immunosuppressive therapy while
      those asymptomatic could be followed up without intervention.

PMID- 25052604
TI  - [A multi-center retrospective study of L-asparaginase-based regimens as first
      line treatment in newly diagnosed extranodal NK/T-cell lymphoma].
AB  - OBJECTIVE: To analyze the short-term efficacy, overall survival (OS), and safety
      in newly diagnosed extranodal NK/T-cell lymphoma (ENKTL) patients with L
      asparaginase based regimens or CHOP regimen in combination with radiotherapy as
      first-line treatment. METHODS: Of the total 181 patients diagnosed by imaging and
      pathology, 69 patients received CHOP regimen and 112 patients received L
      asparaginase based regimens. All the patients received radical
      radiotherapy(RT)after 6 cycles of chemotherapy. RESULTS: The overall response
      rates of L-asparaginase-based group and CHOP group were 90.2% and 72.5%,
      respectively (P=0.002). The 1, 2, 5-year OS and progression-free survival (PFS)
      in L-asparaginase-based group were 96.0%, 88.3%, 65.1% and 94.2%, 79.8%, 50.0%,
      respectively. The 1, 2, 5-year OS and PFS in CHOP group were 82.6%, 61.9%, 28.4%
      and 63.8%, 44.0%, 21.0% (P=0.000). CONCLUSION: Compared with CHOP regimen, L
      asparaginase-based chemotherapy is more effective and safe for newly diagnosed
      nasal-type ENKTL.

PMID- 25052605
TI  - [Expression of miR-224 in diffuse large B cell lymphoma and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression of miR-224 in diffuse large B cell
      lymphoma (DLBCL) and its relationship with clinical pathological features and
      prognosis. METHODS: Real-time PCR was used to detect the expression of miR-224 in
      168 DLBCL and 25 normal lymphoid tissues. RESULTS: The expression of miR-224 in
      DLBCL (0.97 +/- 0.33) was significantly lower than that in normal lymphoid
      tissues (1.87 +/- 0.43, P<0.05). There were no significant correlations between
      the miR-224 expression and age (P=0.434), gender (P=0.613) tumors stage
      (P=0.250), IPI (P=0.355) and lactate dehydrogenase (P=0.398). Using the median of
      miRNA-224 expression as threshold, we subdivided patients into low and high
      expression group. The five-year progression-free survival and overall survival
      were significantly lower in low expression group as compared to those in high
      expression group. CONCLUSION: miR-224 expression may play an important role in
      the development and progression of DLBCL and could be prognostic significance.

PMID- 25052607
TI  - [Analysis of clinical and laboratory features of 217 pediatric hemophagocytic
      lymphohistiocytosis].
AB  - OBJECTIVE: To investigate the incidence, clinical symptoms, signs and laboratory
      features of childhood hemophagocytic lymphohistiocytosis (HLH) in China. METHODS:
      A retrospective study was performed on 217 pediatric patients with HLH who were
      admitted to Children's Hospital of Chongqing Medical University from January 2006
      to April 2013. All patients'medical records were reviewed and analyzed. RESULTS:
      The Male to female ratio was 1.11:1. The median onset age was 3 years and 5
      months old (range of 6 months old to 16 years and 9 months old), and the age of
      onset peaked between 1-5 years old (61.3%). The most common causes of HLH was
      infection, especially Epstein-Barr virus-associated HLH (71.0%). Other causes
      included malignant hemophagocytic syndrome (MAHS), macrophage activation syndrome
      (MAS) and so on. The outstanding clinical manifestations including persistent
      fever (100.0%), hepatomegaly (92.6%), splenomegaly (88.4%), and more than half of
      cases with central nervous system involvement and pulmonary manifestations.
      Laboratory data indicated that the most prominent abnormality was elevated
      ferritin (98.0%), and the others were hemophagocytosis in bone marrow (90.7%) and
      coagulation abnormalities (76.5%). Abnormal lymphocytes classification is very
      common in HLH. CONCLUSION: HLH is a heterogeneous disease, with a variety of the
      etiology and clinical manifestations. HLH-2004 diagnostic protocol had
      theoretical basis and clinical operability. The hepatitis damages related
      indicators, lymphocytes classification, central nervous system involvement and
      pulmonary performance can be used as reference value for HLH diagnosis.

PMID- 25052606
TI  - [Effect of CCL3 on osteoblast in myeloma bone disease].
AB  - OBJECTIVE: To culture osteoblast in vitro and evaluate CCL3 receptor CCR1
      expression in patients with multiple myeloma (MM). METHODS: Bone marrow
      osteoblasts from MM patients were cultured in vitro with dexamethasone, beta
      sodium glycerophosphate and vitamin C, which were identified by alkaline
      phosphatase staining, Von Kossa's staining. The CCL3 receptor expression was
      evaluated by flow cytometry. The morphology and quantity of osteoblast were
      observed after exposure to CCL3. RESULTS: Bone marrow osteoblasts from MM
      patients could be cultured in vitro and be identified by positive staining of
      alkaline phosphatase and Von Kossa's. MM-derived osteoblasts expressed higher
      levels of CCR1 (74.48 +/- 7.31)%, compared with normal controls (48.35 +/-
      8.81)%. Calcium deposition of osteoblasts after exposure to CCL3 was less than
      that of controls. CONCLUSION: Bone marrow osteoblasts could be cultured in vitro
      from MM Patients. CCL3 may contribute to the development of myeloma bone disease.

PMID- 25052608
TI  - [Acquired coagulation factor X deficiency: three cases report and literature
      review].
AB  - OBJECTIVE: To deepen the understanding of acquired coagulation factor X (F X)
      deficiency. METHODS: The clinical data of 3 patients were analyzed and related
      literature were reviewed. RESULTS: Case 1, a 57-year-old male, secondary to
      multiple myeloma and amyloidosis, was presented with spontaneous mucous
      hemorrhage with the level of FX:C 1.8%, which kept unchanged after chemotherapy
      with melphalan, glucocorticoid, and thalidomide, and died of primary disease
      progression. Case 2, a 41-year-old male with psoriasis, was presented with
      cerebral and retinal hemorrhage with the level of FX:C 26.8%. The signs of
      hemorrhage were alleviated after the supplement of folic acid, vitamin B12, and
      vitamin K, and transfusion with red blood cells, platelets, and fresh frozen
      plasma. Case 3, a 63-year-old female, associated with high level of lupus
      anticoagulant, was presented with repeated ecchymosis and haemarthrosis with the
      level of FX:C 6.1%, which was refractory to prothrombin complex concentrate,
      methyprednisolone, azathioprine, and rituximab. CONCLUSION: Acquired FX
      deficiency is a rare disorder with variable symptoms. The diagnosis relies on
      history of disease and laboratory test. Currently, there is no standardized
      treatment. The prognosis of acquired FX deficiency is mainly related to the
      underlying disease.

PMID- 25052609
TI  - [Effect of glycolytic inhibitor 3-BrPA on the proliferation and apoptosis of
      mouse splenic lymphocytes in mixed lymphocytes culture].
AB  - OBJECTIVE: To study the effect of glycolytic inhibitor 3-Bromopyruvate (3-BrPA)
      on the proliferation and apoptosis of mouse spleen lymphocytes and explore its
      mechanism. METHODS: An one-way mixed lymphocyte culture (MLC) system was
      established, including BALB/c mouse spleen cells (H-2d) as stimulator and C57BL/6
      mouse spleen cells (H-2b) as responder. With treatment of 3-BrPA at different
      concentrations (0-200 MUmol/L), lymphocyte proliferation capacity was detected by
      the CCK-8 method, the expression of CD3, CD4, and CD8 by flow cytometry, and the
      concentrations of cytokine interleukin (IL)-4 and interferon (IFN)-gamma in the
      supernatant by ELISA. RESULTS: At a middle or high dose (over 20 MUmol/L), 3-BrPA
      displayed a dose-dependent inhibitory effect on lymphocyte proliferation in the
      MLC system. The 50% inhibitory concentration (IC50) were 48.6, 41.2, and 41.9
      MUmol/L after 24, 36, and 48 h culture, respectively. With treatment of 50
      MUmol/L 3-BrPA, the IFN-gamma level [(164.25 +/- 20.14) ng/L] was significantly
      lower, compared with control [(277.61 +/- 18.46) ng/L]. The IL-4 level [(31.06 +/
      6.06) ng/L] was significantly higher, compared with control [(28.64 +/- 3.97)
      ng/L]. Consequently, the IFN-gamma/IL-4 ratio decreased significantly.
      CONCLUSION: These results indicate that 3-BrPA had a significant inhibitory
      effect on the proliferation of mouse spleen lymphocytes cultured in MLC system,
      accompanied with the Th2-biased secretion of cytokines.

PMID- 25052610
TI  - [Effect of rosiglitazone on the expression of HIF1alpha and IGF1 mRNA in
      myeloma].
AB  - OBJECTIVE: To observe the effect of rosiglitazone (RGZ) on the mRNA expression of
      HIF1alpha and IGF1 genes in the myeloma cells and explore possible mechanism of
      angiogenesis inhibition. METHODS: Human myeloma cell line RPMI8226 and primary
      myeloma cells from five patients enriched by using CD138 immunomagnetic beads
      were treated with different concentrations (10, 20, 40 MUmol/L) of RGZ. The mRNA
      expression of HIF1alpha and IGF1 was analyzed in cells treated with RGZ after 48h
      by RT-PCR, The levels of phosphorylated AKT and ERK proteins were detected by
      Western blotting. Bone marrow mononuclear cells from five patients with iron
      deficiency anemia were regarded as control. RESULTS: Higher mRNA expression of
      HIF1alpha and IGF1 genes in RPMI8226 and in primary myeloma cells was showed as
      compared to those in control. Treated with RGZ of 20 MUmol/L after 48 h, the mRNA
      expression of HIF1alpha (1.21 +/- 0.08 vs 0.75 +/- 0.06) and IGF1 (0.62 +/- 0.06
      vs 0.32 +/- 0.04) in RPMI8226 cells was declined as compared to those without RGC
      treatment. The same declination was also seen in primary myeloma cells
      (HIF1alpha: 2.02 +/- 0.16 vs 0.53 +/- 0.04; IGF1: 1.92 +/- 0.13 vs 0.58+/-0.03).
      RGZ could inhibit the expression of pAKT and pERK, nor the total AKT and ERK
      proteins, in RPMI8226 cells in a dose-dependent manner at the concentration of 10
      MUmol/L, 20 MUmol/L, and 40 MUmol/L. CONCLUSION: RGZ could inhibit the mRNA
      expression of HIF1alpha and IGF1. Inhibition of angiogenesis by RGZ may be
      associated with down-regulation of pAKT and pERK expression.

PMID- 25052611
TI  - [Enhanced sensitivity of leukemia cell line KG-1a to activated immune cell
      mediated cytolysis after treated with resveratrol].
AB  - OBJECTIVE: To explore the enhanced sensitivity of leukemia cell line KG-1a to
      activated immune cell-mediated cytolysis after treated with resveratrol. METHODS:
      The value of 50% inhibition concentration (IC50) for KG-1a by resveratrol was
      analyzed using trypan blue staining. Peripheral blood mononuclear cells were
      separated, and then activated by interleukin (IL)-2 and IL-15. The sensitivity of
      KG-1a treated with and without resveratrol to activated immune cell-mediated
      cytolysis was assayed by lactate dehydrogenase (LDH) -releasing assay. The
      expression of tumor necrosis factor related apoptosis inducing ligand (TRAIL) on
      the surface of activated immune cells and its receptors (DR4/5 and DcR1/2) on the
      surface of KG-1a were detected by flow cytometry. RESULTS: Resveratrol could
      inhibit the proliferation of KG-1a and IC50 at 24 h was 25 mmol/L. At a ratio of
      10:1 or 20:1 between effect and target, the cytolytic rates of treated KG-1a by
      activated immune cells were (55.80 +/- 10.88)% and (72.31 +/- 13.06)%,
      significantly higher than (24.96 +/- 9.25)% and (37.93 +/- 5.21)% of untreated KG
      1a (P<0.05). The expression of DR5 on the surface of KG-1a treated with
      resveratrol was (9.05 +/- 3.57)%, significantly higher than (3.11 +/- 0.54)% of
      untreated KG-1a (P<0.05). Conversely, the expression of DcR1 on the surface of
      treated KG-1a was (13.23 +/- 3.56)%, lower than (53.75 +/- 10.51)% of KG-1a
      (P<0.05). When TRAIL pathway on the surface of activated immune cells was
      blocked, the cytolytic rates of treated KG-1a were (35.97 +/- 6.36)% and (49.80
      +/- 10.68)%, significantly lower than (52.92 +/- 6.98)% and (70.73 +/- 9.79)% of
      untreated KG-1a (P<0.05) at the same ratio of effector and target. CONCLUSION:
      Resveratrol could enhance cytolytic sensitivity of KG-1a by activated immune
      cells through TRAIL pathway.

PMID- 25052612
TI  - [Factor VIII gene mutations in 32 hemophilia A patients from Guangxi].

PMID- 25052613
TI  - [Efficacy of FLAG as initial induction chemotherapy followed by autologous
      hematopoietic stem cell transplantation after IBu conditioning regimen in acute
      myeloid leukemia with FLT3 mutations].

PMID- 25052614
TI  - [Infant blastic plasmacytoid dendritic cell tumor: a case report and literature
      review].

PMID- 25052615
TI  - [ACE2-Ang-(1-7)-Mas axis level of local bone marrow in chronic mountain sickness
      patients].

PMID- 25052616
TI  - [Expression level of NLRP3 inflammasome and its clinical significance in multiple
      myeloma].

PMID- 25052617
TI  - [Effect of hypoxia on the growth and apoptosis of the human multiple myeloma cell
      lines RPMI8226].

PMID- 25052618
TI  - [Mechanism and treatment of hepatitis virus-related thrombocytopenia].

PMID- 25052619
TI  - [A case of acute lymphoblastic leukemia with the initial signs of immature
      monoblastic and skin lesions].

PMID- 25052621
TI  - Assessment of pharmacist-led patient counseling in randomized controlled trials:
      a systematic review.
AB  - Background Pharmacists' counseling has improved health-related outcomes in many
      acute and chronic conditions. Several studies have shown how pharmacists have
      been contributing to reduce morbidity and mortality related to drug-therapy
      (MMRDT). However, there still is a lack of reviews that assemble evidence-based
      clinical pharmacists' counseling. Equally, there is also a need to understand
      structure characteristics, processes and technical contents of these clinical
      services. Aim of the review To review the structure, processes and technical
      contents of pharmacist counseling or education reported in randomized controlled
      trials (RCT) that had positive health-related outcomes. Methods We performed a
      systematic search in specialized databases to identify RCT published between 1990
      and 2013 that have evaluated pharmacists' counseling or educational interventions
      to patients. Methodological quality of the trials was assessed using the Jadad
      scale. Pharmacists' interventions with positive clinical outcomes (p < 0.05) were
      evaluated according to patients' characteristics, setting and timing of
      intervention, reported written and verbal counseling. Results 753 studies were
      found and 101 RCT matched inclusion criteria. Most of the included RCTs showed a
      Jadad score between two (37 studies) and three (32 studies). Pharmacists were
      more likely to provide counseling at ambulatories (60 %) and hospital discharge
      (25 %); on the other hand pharmacists intervention were less likely to happen
      when dispensing a medication. Teaching back and explanations about the drug
      therapy purposes and precautions related to its use were often reported in RCT,
      whereas few studies used reminder charts, diaries, group or electronic
      counseling. Most of studies reported the provision of a printed material (letter,
      leaflet or medication record card), regarding accessible contents and cultural
      concerned informations about drug therapy and disease. Conclusion Pharmacist
      counseling is an intervention directed to patients' health-related needs that
      improve inter-professional and inter-institutional communication, by
      collaborating to integrate health services. In spite of reducing MMRDT, we found
      that pharmacists' counseling reported in RCT should be better explored and
      described in details, hence collaborating to improve medication-counseling
      practice among other countries and settings.

PMID- 25052623
TI  - Hydrogen bonding and proton transfer in cocrystals of 4,4'-bipyridyl and organic
      acids studied using nuclear quadrupole resonance.
AB  - Cocrystals of 4,4'-bipyridyl and several carboxylic acids were grown from the
      methanol solution of the cocrystal formers. Complete (14)N NQR spectra of these
      cocrystals have been measured using (1)H-(14)N nuclear quadrupole double
      resonance. The principal values of the quadrupole coupling tensor are calculated
      from the (14)N NQR frequencies. A large variation in the (14)N quadrupole
      coupling constant between 1.3 MHz and 4.7 MHz is observed. A very low (14)N
      quadrupole coupling constant, characteristic for proton transfer O-H...N -> O(
      )...H-N(+), is observed in 4,4'-bipyridyl-oxalic acid (1 : 1). In 4,4'-bipyridyl
      5-chlorosalycilic acid (1 : 1) the (14)N NQR data show the presence of a short,
      strong N...H...O hydrogen bond. A correlation of the principal values of the
      (14)N quadrupole coupling tensor is observed. The correlation is analyzed in the
      model, where the deformation of the lone pair electron orbital and the change of
      the population of the pi-electron orbital produce the variation of the (14)N
      quadrupole coupling tensor in the hydrogen bonded 4,4'-bipyridyl. The temperature
      variation of the (14)N quadrupole coupling tensor in 4,4'-bipyridyl-5
      chlorosalycilic acid (1 : 1) is analyzed. Proton displacement within the
      N...H...O hydrogen bond and the change of the population of the pi-electron
      orbital at the two nitrogen positions in a 4,4'-bipyridyl molecule in the
      temperature interval between 157 K and 323 K are determined.

PMID- 25052622
TI  - Maternal homocysteine in pregnancy and offspring birthweight: epidemiological
      associations and Mendelian randomization analysis.
AB  - BACKGROUND: Disturbed one-carbon (1-C) metabolism in the mother is associated
      with poor fetal growth but causality of this relationship has not been
      established. METHODS: We studied the association between maternal total
      homocysteine and offspring birthweight in the Pune Maternal Nutrition Study
      (PMNS, Pune, India) and Parthenon Cohort Study (Mysore, India). We tested for
      evidence of causality within a Mendelian randomization framework, using a
      methylenetetrahydrofolatereductase (MTHFR) gene variant rs1801133 (earlier known
      as 677C->T) by instrumental variable and triangulation analysis, separately and
      using meta-analysis. RESULTS: Median (IQR) homocysteine concentration and mean
      (SD) birthweight were 8.6 umol/l (6.7,10.8) and 2642 g (379) in the PMNS and 6.0
      umol/l (5.1,7.1) and 2871 g (443) in the Parthenon study. Offspring birthweight
      was inversely related to maternal homocysteine concentration-PMNS: -22 g/SD [95%
      confidence interval (CI): (-50, 5), adjusted for gestational age and offspring
      gender]; Parthenon: -57 g (-92, -21); meta-analysis: -40 g (-62, -17)]. Maternal
      risk genotype at rs1801133 predicted higher homocysteine concentration [PMNS:
      0.30 SD/allele (0.14, 0.46); Parthenon: 0.21 SD (0.02, 0.40); meta-analysis: 0.26
      SD (0.14, 0.39)]; and lower birthweight [PMNS: -46 g (-102, 11, adjusted for
      gestational age, offspring gender and rs1801133 genotype); Parthenon: -78 g (
      170, 15); meta-analysis: -61 g (-111, -10)]. Instrumental variable and
      triangulation analysis supported a causal association between maternal
      homocysteine concentration and offspring birthweight. CONCLUSIONS: Our findings
      suggest a causal role for maternal homocysteine (1-C metabolism) in fetal growth.
      Reducing maternal homocysteine concentrations may improve fetal growth.

PMID- 25052624
TI  - Effects of the Family Bereavement Program on academic outcomes, educational
      expectations and job aspirations 6 years later: the mediating role of parenting
      and youth mental health problems.
AB  - Experiencing the death of a parent during childhood is associated with a variety
      of difficulties, including lower academic achievement, that have implications for
      functioning in childhood and adulthood. This study examines effects of the Family
      Bereavement Program (FBP), a preventive intervention for parentally-bereaved
      youth and their caregivers, on grade point averages (GPA), educational
      expectations and job aspirations of youths 6 years after the intervention. A
      total of 244 bereaved youths ages 8-16 and their caregivers were randomized to
      either the FBP or a comparison group that received books about bereavement.
      Assessments occurred at pretest, post-test, and 11-month and 6-year follow-ups.
      Direct program effects on educational outcomes and job aspirations 6 years later
      were non-significant, although the program improved educational expectations for
      children with fewer behavior problems at program entry, and GPA for younger
      children. Mediational pathways for program effects on educational outcomes were
      also tested. Program-induced improvements in effective parenting at 11-month
      follow-up were associated with higher GPAs at 6-year follow-up for youth who were
      younger or for whom more time had passed since the loss. Program-induced
      improvements in parenting and teacher-rated youth mental health problems at the 6
      year follow-up mediated program effects on youths' educational expectations for
      those with fewer behavior problems at program entry. The implications of these
      findings for understanding processes related to academic and educational outcomes
      following the death of a parent and for prevention efforts to help bereaved and
      other high-risk children succeed in school are discussed.

PMID- 25052625
TI  - It gets better: future orientation buffers the development of hopelessness and
      depressive symptoms following emotional victimization during early adolescence.
AB  - Research consistently has linked hopelessness to a range of negative outcomes,
      including depression, during adolescence. Although interpersonal stressors such
      as familial and peer emotional victimization have been found to contribute to
      hopelessness, less research has examined whether adolescents with a greater
      tendency to think about and plan for the future (i.e., future orientation) are
      protected against the development of hopelessness, particularly in the context of
      negative events. Thus, the current study evaluated whether peer and familial
      emotional victimization predicted increases in hopelessness more strongly among
      adolescents with a weaker future orientation than those with a stronger
      orientation towards the future, and whether hopelessness in turn predicted
      increases in depression. In a diverse sample of 259 early adolescents (54%
      female; 51% African American; Mage = 12.86 years), both peer and familial
      emotional victimization predicted increases in hopelessness more strongly among
      adolescents with weaker future orientations than among those with stronger future
      orientations. Further, moderated mediation analyses revealed that hopelessness
      significantly mediated the relationship between emotional victimization and
      increases in depressive symptoms more strongly among adolescents with weaker
      orientations towards the future compared to those with stronger future
      orientations. These findings indicate that adolescents' tendency to think about
      the future may impact whether emotional victimization induces hopelessness and
      ultimately depressive symptoms during early adolescence. Results have important
      implications regarding intervention and prevention of depression during the
      critical developmental period of adolescence.

PMID- 25052626
TI  - Exposure and response prevention process predicts treatment outcome in youth with
      OCD.
AB  - Recent research on the treatment of adults with anxiety disorders suggests that
      aspects of the in-session exposure therapy process are relevant to clinical
      outcomes. However, few comprehensive studies have been conducted with children
      and adolescents. In the present study, 35 youth diagnosed with primary obsessive
      compulsive disorder (OCD; M age = 12.9 years, 49% male, 63% Caucasian) completed
      12 sessions of exposure and response prevention (ERP) in one of two treatment
      conditions as part of a pilot randomized controlled testing of a family focused
      intervention for OCD. Key exposure process variables, including youth self
      reported distress during ERP and the quantity and quality of ERP completed, were
      computed. These variables were examined as predictors of treatment outcomes
      assessed at mid-treatment, post-treatment, and three-month follow-up, partialing
      treatment condition. In general, greater variability of distress during ERP and
      completing a greater proportion of combined exposures (i.e., exposures targeting
      more than one OC symptom at once) were predictive of better outcomes. Conversely,
      greater distress at the end of treatment was generally predictive of poorer
      outcomes. Finally, several variables, including within- and between-session
      decreases in distress during ERP, were not consistently predictive of outcomes.
      Findings signal potentially important facets of exposure for youth with OCD and
      have implications for treatment. A number of results also parallel recent
      findings in the adult literature, suggesting that there may be some continuity in
      exposure processes from child to adult development. Future work should examine
      additional measures of exposure process, such as psychophysiological arousal
      during exposure, in youth.

PMID- 25052627
TI  - We need more nurses to ensure 'good deaths'.

PMID- 25052629
TI  - Nurse calls for Commons debate on controversial Assisted Dying Bill.

PMID- 25052628
TI  - Robotic patient used to train academics.

PMID- 25052631
TI  - Staff to have greater say with 'mutual' model.

PMID- 25052630
TI  - New senior nurses' group will offer advice to NMC council on proposals and
      strategy.

PMID- 25052632
TI  - Budget pressures may lead to diluted skill mix.

PMID- 25052633
TI  - Website will help to keep children healthy.

PMID- 25052634
TI  - Nurse loses fourth employment tribunal against former employer.

PMID- 25052635
TI  - Nurse-led online service helps prostate worries.

PMID- 25052636
TI  - Antenatal and postnatal update.

PMID- 25052638
TI  - Mental health support needed to prevent suicides after discharge.

PMID- 25052639
TI  - Stay hydrated for healthier living.

PMID- 25052640
TI  - Campaign to end rip-off hospital car parking fees reaches prime minister.

PMID- 25052641
TI  - Hospital buys first world war book.

PMID- 25052643
TI  - Trust taken out of special measures now has a 'proud, engaged workforce'.

PMID- 25052645
TI  - NICE safe staffing guidance could save the NHS L 700 million a year.

PMID- 25052646
TI  - Wright angle--Stephen Wright's monthly take on nursing in the news.

PMID- 25052647
TI  - Act now to avoid winter deaths.

PMID- 25052653
TI  - Rising to the sickle cell challenge.

PMID- 25052654
TI  - Put safety first when delegating your work.

PMID- 25052655
TI  - For Queen, country and colleagues.

PMID- 25052664
TI  - Imperial War Museum--First World War centenary.

PMID- 25052668
TI  - Robot nurses may lack compassion, but they won't be asking for a pay rise.

PMID- 25052669
TI  - Hospitals need to take greater strides towards sustainability.

PMID- 25052670
TI  - Nurses in Wales want, need and deserve the tools to do their job.

PMID- 25052671
TI  - We are not alone in our fight against public service cuts.

PMID- 25052672
TI  - How can your workplace foster a culture of health and fitness?

PMID- 25052673
TI  - Luton and Dunstable hospital's nurses league celebrates 25 years.

PMID- 25052675
TI  - Involving patients in the assessment of nursing students.
AB  - Enabling patients, service users and carers to participate in the education of
      students in the healthcare sector is widely espoused, both in the literature and
      by professional regulatory bodies. This article focuses on one aspect of this:
      the issue of patient involvement in the assessment of nursing students in the
      practice setting. The challenges and complexities that may arise are explored,
      and recommendations are made for further work in this area. 

PMID- 25052676
TI  - Clostridium difficile infection: nursing considerations.
AB  - Clostridium difficile is a bacterium which commonly causes diarrhoea in
      inpatients. C. difficile affects hospitalised patients worldwide and can pose a
      significant risk to patients. This article explores the transmission and risk
      factors for C. difficile infection (CDI). There are many aspects to the
      prevention and control of CDI: appropriate antibiotic use, early instigation and
      maintenance of prevention and control strategies, and high standards of
      environmental cleanliness, education, and surveillance. This article discusses
      the role of the nurse in each of these prevention and control activities. 

PMID- 25052677
TI  - Advanced cardiac examination: the arterial pulse.
AB  - The pulse is a significant indicator of health and can provide valuable
      information to help make an accurate diagnosis. All nurses should be competent in
      taking and interpreting the pulse, and developing their expertise in this vital
      sign. Arterial pulses can be examined at various sites, and this article focuses
      on techniques for palpating radial, brachial and carotid pulses. 

PMID- 25052678
TI  - Oral cancer.

PMID- 25052679
TI  - Delivering the facts.

PMID- 25052681
TI  - The right kind of relationship.

PMID- 25052682
TI  - 'Surprised and honoured'.

PMID- 25052683
TI  - Student life--a fresh view of dementia.

PMID- 25052686
TI  - Ionizing radiation induces tumor cell lysyl oxidase secretion.
AB  - BACKGROUND: Ionizing radiation (IR) is a mainstay of cancer therapy, but
      irradiation can at times also lead to stress responses, which counteract IR
      induced cytotoxicity. IR also triggers cellular secretion of vascular endothelial
      growth factor, transforming growth factor beta and matrix metalloproteinases,
      among others, to promote tumor progression. Lysyl oxidase is known to play an
      important role in hypoxia-dependent cancer cell dissemination and metastasis.
      Here, we investigated the effects of IR on the expression and secretion of lysyl
      oxidase (LOX) from tumor cells. METHODS: LOX-secretion along with enzymatic
      activity was investigated in multiple tumor cell lines in response to
      irradiation. Transwell migration assays were performed to evaluate invasive
      capacity of naive tumor cells in response to IR-induced LOX. In vivo studies for
      confirming IR-enhanced LOX were performed employing immunohistochemistry of tumor
      tissues and ex vivo analysis of murine blood serum derived from locally
      irradiated A549-derived tumor xenografts. RESULTS: LOX was secreted in a dose
      dependent way from several tumor cell lines in response to irradiation. IR did
      not increase LOX-transcription but induced LOX-secretion. LOX-secretion could not
      be prevented by the microtubule stabilizing agent patupilone. In contrast,
      hypoxia induced LOX-transcription, and interestingly, hypoxia-dependent LOX
      secretion could be counteracted by patupilone. Conditioned media from irradiated
      tumor cells promoted invasiveness of naive tumor cells, while conditioned media
      from irradiated, LOX- siRNA-silenced cells did not stimulate their invasive
      capacity. Locally applied irradiation to tumor xenografts also increased LOX
      secretion in vivo and resulted in enhanced LOX-levels in the murine blood serum.
      CONCLUSIONS: These results indicate a differential regulation of LOX-expression
      and secretion in response to IR and hypoxia, and suggest that LOX may contribute
      towards an IR-induced migratory phenotype in sublethally-irradiated tumor cells
      and tumor progression.

PMID- 25052687
TI  - Considering harm and safety in youth mental health: a call for attention and
      action.
AB  - The possibility of harm from mental health provision, and in particular harm from
      youth mental health provision, has been largely overlooked. We contend that if we
      continue to assume youth mental health services can do no harm, and all that is
      needed is more services, we continue to risk the possibility that the safety of
      children and young people is unintentionally compromised. We propose a three
      level framework for considering harm from youth mental health provision (1.
      ineffective engagement, 2. ineffective practice and 3. adverse events) and
      suggest how this framework could be used to support quality improvement in
      services. 

PMID- 25052688
TI  - Direct determination of chemical oxygen demand by anodic decomposition of organic
      compounds at a diamond electrode.
AB  - Chemical oxygen demand (COD) was measured directly with a simple electrochemical
      method using a boron-doped diamond (BDD) electrode. By applying a highly positive
      potential (+2.5 V vs Ag/AgCl) to an aqueous electrolyte containing potassium
      hydrogen phthalate, glucose, and lactic acid or sodium dodecylbenzenesulfonate
      using a BDD electrode, an anodic current corresponding to the electrolytic
      decomposition of these organic compounds was observed. No such current was seen
      on glassy carbon or platinum electrodes due to a significant background current
      caused by the oxygen evolution reaction. The electric charge for the anodic
      current observed at the BDD electrode was found to be consistent with the
      theoretical charge required for the electrolytic decomposition of the organic
      compounds to CO2 and was used to calculate COD. This analysis was performed by a
      simple I-t measurement at constant potential using a BDD electrode, and no
      calibration was needed. This new simple indicator, "ECOD" (electrochemical oxygen
      demand), will be useful for continuous monitoring of industrial wastewater with
      low protein concentrations and on-site instant analysis of natural water with a
      BDD electrode-based portable ECOD meter. 

PMID- 25052689
TI  - Use of (99m)Tc-anti-TNF-alpha scintigraphy in a patient with non-radiographic
      axial spondyloarthritis.
AB  - The aim of this study was to describe the use of (99m)Tc-anti-TNF-alpha
      scintigraphy for detecting inflammation of the sacroiliac joints in a patient
      with non-radiographic axial spondyloarthritis. A 47-year-old female patient, non
      smoker and non-drinker, complained of a low back pain inflammation, which began 4
      years before her condition have exacerbated to morning stiffness and anterior
      uveitis in the last 6 months. Initially diagnosed as mechanical low back pain,
      she irregularly took non-steroidal anti-inflammatory drugs and corticosteroids,
      without significant long-lasting results. Radiographic findings were negative.
      There was increased uptake of (99m)Tc-anti-TNF-alpha in an area corresponding to
      the topography of ileum and sacroiliac right joint upon (99m)Tc-anti-TNF-alpha
      scintigraphy. Magnetic resonance imaging (MRI), the most used image diagnosis
      tool, showed minimum impregnation of gadolinium in the right sacroiliac joint and
      at the iliac face of the inferior third of the right sacroiliac joint. We suggest
      that (99m)Tc-anti-TNF-alpha can facilitate early diagnosis of patients with non
      radiographic axial spondyloarthritis. More studies are now ongoing. 

PMID- 25052690
TI  - Ectopic expression of DAZL gene in goat bone marrow-derived mesenchymal stem
      cells enhances the trans-differentiation to putative germ cells compared to the
      exogenous treatment of retinoic acid or bone morphogenetic protein 4 signalling
      molecules.
AB  - The plasticity of human and murine bone marrow mesenchymal stem cells (BMSCs) has
      been proven by their ability to trans-differentiate to multilineage cells,
      including germ cells. We have investigated ability of goat BMSCs to trans
      differentiate to germ cells with extrinsic (e.g., retinoic acid [RA] and BMP4
      signalling molecules) and intrinsic factor expression (e.g., DAZL gene ectopic
      expression). Having optimized the concentration of RA and BMP4, gBMSCs were
      treated with RA 1 uM) and BMP4 (25 ng/mL), individually and collectively. Both RA
      and BMP4 induced OCT4, MVH, DAZL, STELLA, NANOG and C-KIT expression, but RNF17,
      PIWIL2, STRA8, and SCP3 were only expressed after RA treatment. In terms of an
      endogenous factor, a germ cell specific gene, deleted in Azoospermia-like (DAZL),
      was overexpressed by plasmid and mRNA techniques. Compared with the RA treated
      group, DAZL ectopic expression upregulated the transcription and translation of
      MVH, and SCP3 was also increased at the mRNA level. The mRNA-based method had
      more effect on the germ cells gene expression compared to the plasmid method.
      Ectopic expression of the DAZL gene enhanced trans-differentiation compared to
      the RA-treated group. Knockdown experiments confirmed the pivotal role of DAZL in
      germ cell differentiation. This study provides further information on the
      mechanisms underlying the spermatogenesis, which will guide the derivation of
      post-meiotic germ cells from adult stem cells in vitro.

PMID- 25052691
TI  - Assessment of skeletal muscle proteolysis and the regulatory response to
      nutrition and exercise.
AB  - Skeletal muscle proteolysis is highly regulated, involving complex intramuscular
      proteolytic systems that recognize and degrade muscle proteins, and recycle free
      amino acid precursors for protein synthesis and energy production. Autophagy
      lysosomal, calpain, and caspase systems are contributors to muscle proteolysis,
      although the ubiquitin proteasome system (UPS) is the primary mechanism by which
      actomyosin fragments are degraded in healthy muscle. The UPS is sensitive to
      mechanical force and nutritional deprivation, as recent reports have demonstrated
      increased proteolytic gene expression and activity of the UPS in response to
      resistance and endurance exercise, and short-term negative energy balance.
      However, consuming dietary protein alone (or free amino acids), or as a primary
      component of a mixed meal, may attenuate intramuscular protein loss by down
      regulating proteolytic gene expression and the catabolic activity of the UPS.
      Although these studies provide novel insight regarding the intramuscular
      regulation of skeletal muscle mass, the role of proteolysis in the regulation of
      skeletal muscle protein turnover in healthy human muscle is not well described.
      This article provides a contemporary review of the intramuscular regulation of
      skeletal muscle proteolysis in healthy muscle, methodological approaches to
      assess proteolysis, and highlights the effects of nutrition and exercise on
      skeletal muscle proteolysis.

PMID- 25052692
TI  - Flavoring exposure in food manufacturing.
AB  - Flavorings are substances that alter or enhance the taste of food. Workers in the
      food-manufacturing industry, where flavorings are added to many products, may be
      exposed to any number of flavoring compounds. Although thousands of flavoring
      substances are in use, little is known about most of these in terms of worker
      health effects, and few have occupational exposure guidelines. Exposure
      assessment surveys were conducted at nine food production facilities and one
      flavor manufacturer where a total of 105 area and 74 personal samples were
      collected for 13 flavoring compounds including five ketones, five aldehydes, and
      three acids. The majority of the samples were below the limit of detection (LOD)
      for most compounds. Diacetyl had eight area and four personal samples above the
      LOD, whereas 2,3-pentanedione had three area samples above the LOD. The
      detectable values ranged from 25-3124 ppb and 15-172 ppb for diacetyl and 2,3
      pentanedione respectively. These values exceed the proposed National Institute
      for Occupational Safety and Health (NIOSH) recommended exposure limit for these
      compounds. The aldehydes had the most detectable samples, with each of them
      having >50% of the samples above the LOD. Acetaldehyde had all but two samples
      above the LOD, however, these samples were below the OSHA PEL. It appears that in
      the food-manufacturing facilities surveyed here, exposure to the ketones occurs
      infrequently, however levels above the proposed NIOSH REL were found. Conversely,
      aldehyde exposure appears to be ubiquitous. 

PMID- 25052693
TI  - Statistical evaluation of the feasibility of satellite-retrieved cloud parameters
      as indicators of PM2.5 levels.
AB  - The spatial and temporal characteristics of fine particulate matter (PM2.5,
      particulate matter <2.5 MUm in aerodynamic diameter) are increasingly being
      studied from satellite aerosol remote sensing data. However, cloud cover severely
      limits the coverage of satellite-driven PM2.5 models, and little research has
      been conducted on the association between cloud properties and PM2.5 levels. In
      this study, we analyzed the relationships between ground PM2.5 concentrations and
      two satellite-retrieved cloud parameters using data from the Southeastern Aerosol
      Research and Characterization (SEARCH) Network during 2000-2010. We found that
      both satellite-retrieved cloud fraction (CF) and cloud optical thickness (COT)
      are negatively associated with PM2.5 levels. PM2.5 speciation and meteorological
      analysis suggested that the main reason for these negative relationships might be
      the decreased secondary particle generation. Stratified analyses by season, land
      use type, and site location showed that seasonal impacts on this relationship are
      significant. These associations do not vary substantially between urban and rural
      sites or inland and coastal sites. The statistically significant negative
      associations of PM2.5 mass concentrations with CF and COT suggest that satellite
      retrieved cloud parameters have the potential to serve as predictors to fill the
      data gap left by satellite aerosol optical depth in satellite-driven PM2.5
      models.

PMID- 25052694
TI  - Design and implementation of magnetically maneuverable capsule endoscope system
      with direction reference for image navigation.
AB  - This article describes a novel magnetically maneuverable capsule endoscope system
      with direction reference for image navigation. This direction reference was
      employed by utilizing a specific magnet configuration between a pair of external
      permanent magnets and a magnetic shell coated on the external capsule endoscope
      surface. A pair of customized Cartesian robots, each with only 4 degrees of
      freedom, was built to hold the external permanent magnets as their end-effectors.
      These robots, together with their external permanent magnets, were placed on two
      opposite sides of a "patient bed." Because of the optimized configuration based
      on magnetic analysis between the external permanent magnets and the magnetic
      shell, a simplified control strategy was proposed, and only two parameters, yaw
      step angle and moving step, were necessary for the employed robotic system. Step
      by-step experiments demonstrated that the proposed system is capable of
      magnetically maneuvering the capsule endoscope while providing direction
      reference for image navigation. 

PMID- 25052695
TI  - An experimental method for the assessment of color simulation tools.
AB  - The Simulcheck method for evaluating the accuracy of color simulation tools in
      relation to dichromats is described and used to test three color simulation
      tools: Variantor, Coblis, and Vischeck. A total of 10 dichromats (five
      protanopes, five deuteranopes) and 10 normal trichromats participated in the
      current study. Simulcheck includes two psychophysical tasks: the Pseudoachromatic
      Stimuli Identification task and the Minimum Achromatic Contrast task. The
      Pseudoachromatic Stimuli Identification task allows determination of the two
      chromatic angles (h(uv) values) that generate a minimum response in the yellow
      blue opponent mechanism and, consequently, pseudoachromatic stimuli (greens or
      reds). The Minimum Achromatic Contrast task requires the selection of the gray
      background that produces minimum contrast (near zero change in the achromatic
      mechanism) for each pseudoachromatic stimulus selected in the previous task (L(R)
      values). Results showed important differences in the colorimetric transformations
      performed by the three evaluated simulation tools and their accuracy levels.
      Vischeck simulation accurately implemented the algorithm of Brettel, Vienot, and
      Mollon (1997). Only Vischeck appeared accurate (similarity in huv and L(R) values
      between real and simulated dichromats) and, consequently, could render reliable
      color selections. It is concluded that Simulcheck is a consistent method because
      it provided an equivalent pattern of results for huv and L(R) values irrespective
      of the stimulus set used to evaluate a simulation tool. Simulcheck was also
      considered valid because real dichromats provided expected huv and LR values when
      performing the two psychophysical tasks included in this method.

PMID- 25052697
TI  - Size determines whether specialized expert processes are engaged for recognition
      of faces.
AB  - Many influential models of face recognition postulate specialized expert
      processes that are engaged when viewing upright, own-race faces, as opposed to a
      general-purpose recognition route used for nonface objects and inverted or other
      race faces. In contrast, others have argued that empirical differences do not
      stem from qualitatively distinct processing. We offer a potential resolution to
      this ongoing controversy. We hypothesize that faces engage specialized processes
      at large sizes only. To test this, we measured recognition efficiencies for a
      wide range of sizes. Upright face recognition efficiency increased with size.
      This was not due to better visibility of basic image features at large sizes. We
      ensured this by calculating efficiency relative to a specialized ideal observer
      unique to each individual that incorporated size-related changes in visibility
      and by measuring inverted efficiencies across the same range of face sizes.
      Inverted face recognition efficiencies did not change with size. A qualitative
      face inversion effect, defined as the ratio of relative upright and inverted
      efficiencies, showed a complete lack of inversion effects for small sizes up to 6
      degrees . In contrast, significant face inversion effects were found for all
      larger sizes. Size effects may stem from predominance of larger faces in the
      overall exposure to faces, which occur at closer viewing distances typical of
      social interaction. Our results offer a potential explanation for the
      contradictory findings in the literature regarding the special status of faces.

PMID- 25052696
TI  - A single auditory tone alters the perception of multiple visual events.
AB  - We aimed to show that a single auditory tone crossmodally affects multiple visual
      events using a multiple stream/bounce display (SBD), consisting of two disk pairs
      moving toward each other at equal speeds, coinciding, and then moving apart in a
      two-dimensional (2-D) display. The temporal offsets were manipulated between the
      coincidences of the disk pairs (0 to +/-240 ms) by staggering motion onset
      between the pairs. A tone was presented at the coincidence timing of one of the
      disk pairs on half of the trials. Participants judged whether the disks in each
      of two pairs appeared to stream through or bounce off each other. Results show
      that a tone presented at either of the disk pairs' coincidence points promoted
      bouncing percepts in both disk pairs compared to no-tone trials. Perceived
      bouncing persisted in the disk-pair whose coincidence was offset 60 ms before and
      up to more than 120 ms after the audiovisual coincidence timing of the other disk
      pair. The temporal window of bounce promotion was comparable to that obtained
      with a conventional SBD. The interaction of a single auditory event and multiple
      visual events was also modulated by the kind of experimental task (the
      stream/bounce or simultaneity judgments). These findings suggest that, using a
      single auditory cue, the perceptual system resolves the ambiguity of the motion
      of multiple disk pairs presented within the conventional temporal window of
      crossmodal interaction.

PMID- 25052698
TI  - A phase 1 dose escalation study of idarubicin combined with methotrexate,
      vindesine, and prednisolone for untreated elderly patients with primary central
      nervous system lymphoma. The GOELAMS LCP 99 trial.
AB  - Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients
      remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based
      regimen including idarubicin, a phase 1 multicenter dose escalation study was
      conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty
      five immunocompetent patients with PCNSL were enrolled. The median age was 65
      years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose
      of 3 g/m(2) (6-hr intravenous [IV]) and 3 mg/m(2) IV on day 1, respectively.
      Prednisolone (PRED) was given at the fixed dose of 60 mg/m(2) (IV or orally) on
      days 1-5. Idarubicin was escalated in increments of 2 mg/m(2) with doses ranging
      from 12-18 mg/m(2) IV on day 1. Treatment was repeated three times every 3 weeks.
      Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7
      days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2.
      The MTD of idarubicin was reached at 16 mg/m(2) . At this level, the main
      haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade
      3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious
      disease (5%) and grade 2 renal failure (9%). For the study population, median
      overall and progression-free survival were 19 and 13 months, respectively. Our
      study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and
      PRED, should be 16 mg/m(2) . Further studies will be necessary to challenge a
      standard treatment in elderly patients with PCNSL.

PMID- 25052699
TI  - Which method of left atrium size quantification is the most accurate to recognize
      thromboembolic risk in patients with non-valvular atrial fibrillation?
AB  - BACKGROUND: Left atrial (LA) size is a predictor of cardiovascular outcomes in
      patients in sinus rhythm, whereas conflicting results have been found in atrial
      fibrillation (AF). This study aims to: (1) Evaluate the accuracy of LA size to
      identify surrogate markers of an increased thromboembolic risk in patients with
      AF; (2) Assess the best method to evaluate LA size in this setting. METHODS:
      Cross-sectional study enrolling 500 consecutive patients undergoing transthoracic
      and transesophageal echocardiography evaluation during a non-valvular AF episode.
      LA size was measured on transthoracic echocardiography using several methods:
      anteroposterior diameter, area in four-chamber view, and volumes by the
      ellipsoid, single- and biplane area-length formulas. Surrogate markers of stroke
      were evaluated by transesophageal echocardiography: LA appendage (LAA) thrombus,
      LAA low flow velocities, dense spontaneous echocardiographic contrast and LA
      abnormality. RESULTS: Except for non-indexed anteroposterior diameter, increased
      LA size quantified by all the other methods showed a moderate to high
      discriminatory power to identify all the surrogate markers of stroke. A higher
      accuracy was observed for indexed LA area in four-chamber view (LAA thrombus: AUC
      = 0.708, CI95% 0.644- 0.772, p<0.001; LAA low flow velocities: AUC = 0.733, CI95%
      0.674- 0.793, p<0.001; dense spontaneous echocardiographic contrast: AUC = 0.693,
      CI95% 0.638- 0.748, p<0.001; LA abnormality: AUC = 0.705, CI95% 0.654-0.755,
      p<0.001), indexed single-plane area-length volume (LAA thrombus: AUC = 0.701,
      CI95% 0.633-0.770, p<0.001; LAA low flow velocities: AUC = 0.726, CI95% 0.660
      0.792, p<0.001; dense spontaneous echocardiographic contrast: AUC = 0.673, CI95%
      0.611-0.736, p<0.001; LA abnormality: AUC = 0.687, CI95% 0.629-0.744, p<0.001),
      and indexed biplane area-length volume (LAA thrombus: AUC = 0.707, CI95% 0.626
      0.788, p<0.001; LAA low flow velocities: AUC = 0.737, CI95% 0.664-0.810, p<0.001;
      dense spontaneous echocardiographic contrast: AUC = 0.651, CI95% 0.578-0.724,
      p<0.001; LA abnormality: AUC = 0.683, CI95% 0.617-0.749, p<0.001), without
      significant difference between them. Indexed LA area in four-chamber view and
      indexed area-length volumes also were independent predictors of surrogate markers
      of stroke. CONCLUSIONS: Left atrium enlargement is associated with an increased
      prevalence of surrogate markers of stroke in patients with non-valvular AF.
      Indexed LA area in four-chamber view and indexed area-length volumes displayed
      the strongest association.

PMID- 25052700
TI  - Massive conformational changes during thermally induced self-metalation of 2H
      tetrakis-(3,5-di-tert-butyl)-phenylporphyrin on Cu(111).
AB  - Based on a combined scanning tunnelling microscopy and X-ray photoelectron
      spectroscopy study we present detailed insights into pronounced changes of long
      range order and intramolecular conformation during the self-metalation of 2H
      5,10,15,20-tetrakis-(3,5-di-tert-butyl)-phenylporphyrin (2HTTBPP) to CuTTBPP on
      Cu(111). Upon metalation, the porphyrin literally "pops up" from the surface, due
      to a drastically reduced molecule-substrate interaction. 

PMID- 25052701
TI  - Assisting manual literature curation for protein-protein interactions using
      BioQRator.
AB  - The time-consuming nature of manual curation and the rapid growth of biomedical
      literature severely limit the number of articles that database curators can
      scrutinize and annotate. Hence, semi-automatic tools can be a valid support to
      increase annotation throughput. Although a handful of curation assistant tools
      are already available, to date, little has been done to formally evaluate their
      benefit to biocuration. Moreover, most curation tools are designed for specific
      problems. Thus, it is not easy to apply an annotation tool for multiple tasks.
      BioQRator is a publicly available web-based tool for annotating biomedical
      literature. It was designed to support general tasks, i.e. any task annotating
      entities and relationships. In the BioCreative IV edition, BioQRator was tailored
      for protein- protein interaction (PPI) annotation by migrating information from
      PIE the search. The results obtained from six curators showed that the precision
      on the top 10 documents doubled with PIE the search compared with PubMed search
      results. It was also observed that the annotation time for a full PPI annotation
      task decreased for a beginner-intermediate level annotator. This finding is
      encouraging because text-mining techniques were not directly involved in the full
      annotation task and BioQRator can be easily integrated with any text-mining
      resources. Database URL: http://www.bioqrator.org/.

PMID- 25052702
TI  - Standardized description of scientific evidence using the Evidence Ontology
      (ECO).
AB  - The Evidence Ontology (ECO) is a structured, controlled vocabulary for capturing
      evidence in biological research. ECO includes diverse terms for categorizing
      evidence that supports annotation assertions including experimental types,
      computational methods, author statements and curator inferences. Using ECO,
      annotation assertions can be distinguished according to the evidence they are
      based on such as those made by curators versus those automatically computed or
      those made via high-throughput data review versus single test experiments.
      Originally created for capturing evidence associated with Gene Ontology
      annotations, ECO is now used in other capacities by many additional annotation
      resources including UniProt, Mouse Genome Informatics, Saccharomyces Genome
      Database, PomBase, the Protein Information Resource and others. Information on
      the development and use of ECO can be found at http://evidenceontology.org. The
      ontology is freely available under Creative Commons license (CC BY-SA 3.0), and
      can be downloaded in both Open Biological Ontologies and Web Ontology Language
      formats at http://code.google.com/p/evidenceontology. Also at this site is a
      tracker for user submission of term requests and questions. ECO remains under
      active development in response to user-requested terms and in collaborations with
      other ontologies and database resources. Database URL: Evidence Ontology Web
      site: http://evidenceontology.org. 

PMID- 25052704
TI  - Postural control at 4 years in very preterm children compared with term-born
      peers.
AB  - AIM: To compare postural control at 4 years' corrected age in very preterm
      children (VPT; <30wks gestational age) with term-born (>37wks gestational age)
      comparison participants. METHOD: Ninety VPT children (45 males, 45 females; mean
      age at assessment 4y 1mo; mean birthweight 1022g; mean gestational age 27.3wks)
      and 36 term comparison participants (17 males, 19 females; mean age at assessment
      4y; mean birthweight 3507g; mean gestational age 39.4wks) were assessed for
      postural stability with a portable force plate, the Wii Balance Board. Tasks
      included static two-limbed standing with eyes open, eyes closed, eyes open on a
      foam mat, eyes closed on a foam mat, a cognitive dual task, and single leg
      standing on each limb. The cognitive dual task involved showing the participants
      a series of pictures that appeared on screen at 2-second intervals. Impaired
      postural control was defined as increased postural sway measured by centre of
      pressure path-length velocity. Functional performance was assessed during dynamic
      jumping and hopping tasks using the outcome measure flight time, with shorter
      time indicating worse performance. RESULTS: VPT children had impaired static and
      dynamic balance, with increased postural sway under all conditions, and reduced
      flight times compared with children born at term. When results were adjusted for
      body weight, the only group differences in postural control were in the cognitive
      dual task (cm/s; mean difference 0.6; 95% confidence interval [CI] 0.02, 1.2;
      p=0.04) and flight times (ms; jumping; mean difference -26.0; 95% CI -47.1, -5.0;
      p=0.02; left leg hopping; mean difference -30.1; 95% CI -48.5, -11.8; p=0.002).
      INTERPRETATION: VPT children demonstrated reduced postural control at 4 years of
      age compared with term-born children when presented with a cognitive dual task.
      They also performed worse during jumping and hopping tasks.

PMID- 25052703
TI  - APADB: a database for alternative polyadenylation and microRNA regulation events.
AB  - Alternative polyadenylation (APA) is a widespread mechanism that contributes to
      the sophisticated dynamics of gene regulation. Approximately 50% of all protein
      coding human genes harbor multiple polyadenylation (PA) sites; their selective
      and combinatorial use gives rise to transcript variants with differing length of
      their 3' untranslated region (3'UTR). Shortened variants escape UTR-mediated
      regulation by microRNAs (miRNAs), especially in cancer, where global 3'UTR
      shortening accelerates disease progression, dedifferentiation and proliferation.
      Here we present APADB, a database of vertebrate PA sites determined by 3' end
      sequencing, using massive analysis of complementary DNA ends. APADB provides
      (A)PA sites for coding and non-coding transcripts of human, mouse and chicken
      genes. For human and mouse, several tissue types, including different cancer
      specimens, are available. APADB records the loss of predicted miRNA binding sites
      and visualizes next-generation sequencing reads that support each PA site in a
      genome browser. The database tables can either be browsed according to organism
      and tissue or alternatively searched for a gene of interest. APADB is the largest
      database of APA in human, chicken and mouse. The stored information provides
      experimental evidence for thousands of PA sites and APA events. APADB combines 3'
      end sequencing data with prediction algorithms of miRNA binding sites, allowing
      to further improve prediction algorithms. Current databases lack correct
      information about 3'UTR lengths, especially for chicken, and APADB provides
      necessary information to close this gap. Database URL:
      http://tools.genxpro.net/apadb/.

PMID- 25052705
TI  - The Brazilian founder mutation TP53 p.R337H is uncommon in Portuguese women
      diagnosed with breast cancer.
AB  - Since the first studies reporting the TP53 p.R337H mutation as founder mutation
      in Southern and Southeastern Brazil, there has been controversy on its origin.
      Preliminary analysis of a small subset of Brazilian mutation carriers revealed
      that the haplotype incided on a Caucasian background. The vast majority of
      carriers identified today reside in Brazil or, if identified in other countries,
      are Brazilian immigrants. To our knowledge, the only two exceptions of carriers
      without a recognizable link with Brazil are two European families, from Portugal
      and Germany. Haplotype analysis in the Portuguese family revealed the same
      haplotype identified in Brazilian individuals, but in the German family, a
      distinct haplotype was found. Knowing that a significant proportion of women with
      breast cancer (BC) in Southern Brazil are p.R337H carriers, we analyzed p.R337H
      in a Portuguese cohort of women diagnosed with this disease. Median age at
      diagnosis among the first 573 patients tested was 60 years and 100 (17.4%)
      patients had been diagnosed at or under the age of 45 years. Mutation screening
      failed to identify the mutation in the 573 patients tested. These results are in
      contrast with the mutation frequency observed in a study including 815 BC
      affected women from Brazil, in which carrier frequencies of 12.1 and 5.1% in pre-
      and postmenopausal women were observed, respectively. These findings suggest that
      the Brazilian founder mutation p.R337H, the most frequent germline TP53 mutation
      reported to date, is not a common germline alteration in Portuguese women
      diagnosed with BC.

PMID- 25052706
TI  - Sexual desire discrepancy as a feature, not a bug, of long-term relationships:
      women's self-reported strategies for modulating sexual desire.
AB  - INTRODUCTION: Sexual desire discrepancy is commonly reported by couples in long
      term romantic relationships. Given the idiosyncratic nature of desire, and the
      lack of a "one size fits all" model approach to address desire concerns, it is
      useful to understand more about the range of ways that women and their partners
      modulate sexual desire. AIM: This study aims to assess women's strategies to
      influence their sexual desire and the self-reported effectiveness of these
      strategies. METHODS: One hundred seventy-nine women who had been in a
      relationship with a male partner for 5+ years completed an anonymous Internet
      based survey. MAIN OUTCOME MEASURES: Participants responded to three open-ended
      items about the strategies they use to address desire issues and how helpful
      those strategies are. RESULTS: The most common responses regarding what
      participants did to get desire back on track included: communication, trying to
      meet partner's needs, having sex without desire, and having patience/letting time
      work out the problem. Women also mentioned several specific strategies they had
      employed: communication, scheduling sex, lingerie, and a date night. However, a
      large number of women discussed that the issue was not resolved, and they were
      dissatisfied with attempted strategies. CONCLUSIONS: This research provides
      valuable insight into the construction of women's sexual desire and the
      strategies used to navigate sexual desire in long-term relationships.

PMID- 25052707
TI  - Bioinformatic investigation of the cost management strategies of five oral
      microbes.
AB  - Some amino acids are more energetically costly to synthesize de novo, therefore
      many microbes have evolved to regulate the metabolic expenditure of the cell and
      reduce the energy burden of extracellular unrecyclable proteins. Several oral
      bacterial species take up amino acids and peptides obtained from proteolysis of
      host proteins and hence do not rely only on de novo synthesis. The aim of this
      study was to investigate if five oral bacterial species implement cost management
      strategies to reduce the energy burden of extracellular unrecyclable proteins.
      Since the relative de novo amino acid synthesis costs are proportional to the
      masses of the amino acids, the energy costs of producing proteins were assessed
      by calculating the mean amino acid mass for each protein. For Porphyromonas
      gingivalis, Treponema denticola, Tannerella forsythia, Prevotella intermedia and
      Streptococcus sanguinis, the outer membrane/extracellular proteins are made up of
      a much larger percentage of lower average mass amino acids whereas cytoplasmic
      proteins are made up of a larger proportion of higher average mass amino acid
      residues. These results are consistent with the five oral bacterial species
      employing energy-saving mechanisms in the production of extracellular
      unrecyclable proteins. Interestingly, the P. gingivalis and S. sanguinis genomes
      exhibited significantly lower predicted mean amino acid masses compared with
      those of the genomes of the other three species, suggesting that this may provide
      them with an energy advantage with respect to protein biosynthetic cost.

PMID- 25052708
TI  - Recent seizure activity alters motor organization in frontal lobe epilepsy as
      revealed by task-based fMRI.
AB  - PURPOSE: Patients with frontal lobe epilepsy (FLE) commonly demonstrate motor
      impairments, suggesting that frontal lobe seizures affect motor function.
      However, the underlying mechanisms of these deficits are not known, nor has any
      study systematically examined motor organization in these patients. We therefore
      examined cortical motor organization in a group of adult patients with FLE, using
      task-based fMRI. METHODS: Eleven right FLE patients, six left FLE patients, and
      ten control subjects underwent task-based fMRI. Two tasks were performed using
      the right and left hands separately, and both hands together. The first task was
      a finger-tapping task and the second task was a more complex coordination task.
      Functional MR data were compared between patient groups and controls. A
      laterality index of brain activation was also calculated between the epileptic
      and healthy hemisphere to determine hemispheric dominance during task performance
      to explore its relationship with a variety of patient-specific epilepsy factors.
      RESULTS: Overall, right FLE patients demonstrated decreased BOLD activity in the
      epileptic hemisphere and increased BOLD activity in the healthy hemisphere
      compared to controls (p<0.05). The comparison of left FLE patients to controls
      provided less conclusive differences, possibly due to the low number of left FLE
      patients studied. Laterality indices of the coordination task were positively
      correlated to the number of months since the last seizure in both patient groups
      (right FLE: rs=0.779, left FLE: rs=0.943). Patients that had experienced a recent
      seizure relied more on the sensorimotor cortex of the healthy hemisphere during
      task performance, compared to those that were relatively seizure free (p<0.05).
      SIGNIFICANCE: Patients with FLE exhibited changes in motor BOLD activity that was
      dependent on the duration of seizure freedom. These results demonstrate the
      presence of seizure-related alteration of cortical motor organization in FLE,
      which may underlie the motor deficits seen in these patients.

PMID- 25052709
TI  - Effect of partial drug withdrawal on the lateralization of interictal
      epileptiform discharges and its relationship to surgical outcome in patients with
      hippocampal sclerosis.
AB  - OBJECTIVE: To assess changes in the relative lateralization of interictal
      epileptiform discharges (IEDs) and interictal EEG prognostic value in terms of
      surgical outcome between periods with full medication (FMP) and reduced
      medication (RMP) in patients with temporal lobe epilepsy (TLE) associated with
      hippocampal sclerosis (HS). METHODS: Interictal scalp EEGs of 43 patients were
      evaluated for the presence of IEDs separately in a waking state (WS) and sleeping
      state (SS) during FMP and RMP. In each period, patients were categorized as
      having unitemporal or bitemporal IEDs. Surgical outcome was classified at year 1
      after surgery and at last follow-up visit as Engel I or Engel II-IV; and
      alternatively as completely seizure-free or not seizure-free. RESULTS: There were
      significant changes in relative IED lateralization between FMP and RMP during SS.
      The representation of patients with unitemporal IEDs declined from 37 (86%) in
      FMP during SS to 25 (58%) in RMP during SS (p=0.003). At year 1 after surgery,
      the relative IED lateralization is a predictive factor for surgical outcome
      defined as Engel I vs. Engel II-IV in both FMP during WS (p=0.037) and during SS
      (p=0.007), and for surgical outcome defined as completely seizure-free vs. not
      seizure-free in FMP during SS (p=0.042). At last follow up visit, the relative
      IED lateralization is a predictor for outcome defined as Engel I vs. Engel II-IV
      in FMP during SS (p=0.020), and for outcome defined as completely seizure-free
      vs. not seizure-free in both FMP during WS (p=0.043) and in FMP during SS
      (p=0.015). When stepwise logistic regression analysis was applied, only FMP
      during SS was found to be an independent predictor for surgical outcome at year 1
      after surgery (completely seizure-free vs. not seizure-free p=0.032, Engel I vs.
      Engel II-IV p=0.006) and at last follow-up visit (completely seizure-free vs. not
      seizure-free p=0.024, Engel I vs. Engel II-IV p=0.017). Gender was found to be
      independent predictor for surgical efficacy at year 1 if the outcome was defined
      as completely seizure-free vs. not seizure-free (p=0.036). CONCLUSION: The
      predictive value of relative IED lateralization with respect to surgical outcome
      in interictal EEG is present only during FMP; the predictive value decreases with
      the reduction of AEDs caused by the change of relative IED lateralization.

PMID- 25052710
TI  - Growth parameters and childhood epilepsy in Hai District, Tanzania: a community
      based study.
AB  - AIM: This cross-sectional study examined whether growth parameters were
      associated with epilepsy in children living in a rural community in sub-Saharan
      Africa (SSA). MATERIALS AND METHODS: A cross-sectional study was performed in the
      Hai District Demographic Surveillance Site (HDSS), Tanzania in which 6-14 year
      old children with epilepsy (CWE) were identified. Age matched controls were
      randomly selected from the Hai census database for comparison. Anthropometric
      measurements were used to assess the nutritional status of the children and body
      mass index (BMI) calculated. Associations between social, demographic and
      nutritional factors and epilepsy were assessed using multivariable logistic
      regression. RESULTS: 112 CWE were identified and were compared with 113 controls.
      There was no significant difference in the BMI between cases and controls (T
      test, p-value of 0.117). Amongst cases, there were no significant associations
      between BMI and motor difficulties, antiepileptic drug use, cognitive or
      behavioural problems, early-onset epilepsy or seizure frequency. In the whole
      group, BMI was significantly associated with socio-economic status (p=0.037) and
      age. DISCUSSION: There was no significant difference found between CWE and
      matched controls with respect to nutritional status. This suggests that there is
      no causal association between under nutrition and epilepsy in this community.
      Nutritional assessment is still important as part of the comprehensive care of
      CWE.

PMID- 25052711
TI  - Karyological relationships in Indian species of Drimia based on fluorescent
      chromosome banding and nuclear DNA amount.
AB  - The genus Drimia (syn. Urginea), commonly called squill, represents a species
      complex, infrageneric delimitation being ill-defined due to morphological
      variability, population variation within species and polyploidy. In the present
      study, fluorescent chromosome banding and measurements of nuclear DNA content by
      flow cytometry were performed in five Indian species of Drimia: Drimia indica,
      Drimia polyantha, Drimia razii, Drimia wightii and Drimia coromandeliana to
      elucidate taxonomic relationship and obtain possible insights into the
      evolutionary processes within this group. All taxa analyzed exhibited similar
      karyomorphology with subtle differences accounted by nucleolar chromosomes.
      Nuclear DNA content ranged from 20.41 pg/2C in D. polyantha to 40.80 pg/2C in D.
      coromandeliana and was positively correlated with chromosome number (r = 0.67, P
      = 0.02) and total diploid chromatin length (r = 0.59, P = 0.06). Fluorescent
      chromosome banding revealed the presence of CMA(+ve)/DAPI(-ve) signals associated
      with nucleolar chromosomes presumably coincident with NOR in all species and
      unique CMA(+ve) signals in diploid populations of D. indica. Satellite
      polymorphism between homologous NOR-bearing chromosomes was observed which
      supports hybrid origin of the taxon. UPGMA dendrogram and scatter diagrams based
      on karyological parameters indicated a close relationship of D. indica, D. razii
      and D. polyantha while D. wightii and D. coromandeliana appeared distant. D.
      wightii appeared more close to D. indica than to all other species based on
      genome size and karyomorphology. As a whole, D. indica showed high intra-specific
      variability with populations exhibiting intergrading characters with other
      species. In conclusion, it is likely that hybridization followed by reproductive
      isolation of polymorphic forms arising by adaptation to different ecological
      niches resulted in species diversification of Drimia in India, probably from a
      common ancestor similar to D. indica. 

PMID- 25052712
TI  - Mapping change in human pressure globally on land and within protected areas.
AB  - It is widely accepted that the main driver of the observed decline in biological
      diversity is increasing human pressure on Earth's ecosystems. However, the
      spatial patterns of change in human pressure and their relation to conservation
      efforts are less well known. We developed a spatially and temporally explicit map
      of global change in human pressure over 2 decades between 1990 and 2010 at a
      resolution of 10 km(2) . We evaluated 22 spatial data sets representing different
      components of human pressure and used them to compile a temporal human pressure
      index (THPI) based on 3 data sets: human population density, land transformation,
      and electrical power infrastructure. We investigated how the THPI within
      protected areas was correlated to International Union for Conservation of Nature
      (IUCN) management categories and the human development index (HDI) and how the
      THPI was correlated to cumulative pressure on the basis of the original human
      footprint index. Since the early 1990s, human pressure increased 64% of the
      terrestrial areas; the largest increases were in Southeast Asia. Protected areas
      also exhibited overall increases in human pressure, the degree of which varied
      with location and IUCN management category. Only wilderness areas and natural
      monuments (management categories Ib and III) exhibited decreases in pressure.
      Protected areas not assigned any category exhibited the greatest increases. High
      HDI values correlated with greater reductions in pressure across protected areas,
      while increasing age of the protected area correlated with increases in pressure.
      Our analysis is an initial step toward mapping changes in human pressure on the
      natural world over time. That only 3 data sets could be included in our spatio
      temporal global pressure map highlights the challenge to measuring pressure
      changes over time.

PMID- 25052713
TI  - Cadmium induces mitophagy through ROS-mediated PINK1/Parkin pathway.
AB  - CONTEXT AND OBJECTIVE: Recent reports have highlighted the relationship between
      cadmium (Cd) and autophagy, however, whether Cd can activate mitophagy remains
      enigmatic. This study aims to investigate the effects of Cd on mitophagy and its
      potential mechanism. METHODS: Mice were intraperitoneally injected with Cd for 3
      d. Mitochondrial membrane potential (MMP), mitophagosomes, LC3-II/LC3-I ratio,
      PINK1 level and mitochondrial mass were evaluated to indicate the effects of Cd
      on mitophagy. To elucidate the mechanism, reactive oxygen species (ROS) scavenger
      N-acetyl-L-cysteine (NAC) or acetyl-L-carnitine (ALC) as well as the mitophagy
      inhibitor cyclosporine A (CsA) were introduced to verify the role of ROS in
      mitophagy. RESULTS AND CONCLUSIONS: The results showed that Cd significantly
      induced MMP collapse and typical mitophagosomes formation, increased LC3-II/LC3-I
      ratio and PINK1 level, and decreased mitochondrial mass, revealing that Cd could
      induce mitophagy. However, NAC or ALC pretreatment markedly decreased Cd-induced
      ROS and simultaneously rescued MMP and mitochondrial mass, suggesting ROS played
      a crucial role in regulating mitophagy. NAC or ALC also dramatically lessened
      PINK1 level and mitochondrial accumulation of Parkin, indicating that ROS were
      related to PINK1/Parkin pathway. Notably, CsA compromised Cd-induced mitophagy,
      PINK1 accumulation and Parkin translocation while failed to block ROS increase,
      suggesting ROS functioned as an upstream signal for PINK1/Parkin pathway. Taken
      together, the results indicated that Cd induced ROS-mediated mitophagy through
      PINK1/Parkin pathway in kidneys of mice. The present study proposes a new
      perspective to evaluate the nephrotoxicity and its molecular mechanism under Cd
      exposure in vivo.

PMID- 25052714
TI  - Uric acid accumulation in an Arabidopsis urate oxidase mutant impairs seedling
      establishment by blocking peroxisome maintenance.
AB  - Purine nucleotides can be fully catabolized by plants to recycle nutrients. We
      have isolated a urate oxidase (uox) mutant of Arabidopsis thaliana that
      accumulates uric acid in all tissues, especially in the developing embryo. The
      mutant displays a reduced germination rate and is unable to establish autotrophic
      growth due to severe inhibition of cotyledon development and nutrient
      mobilization from the lipid reserves in the cotyledons. The uox mutant phenotype
      is suppressed in a xanthine dehydrogenase (xdh) uox double mutant, demonstrating
      that the underlying cause is not the defective purine base catabolism, or the
      lack of UOX per se, but the elevated uric acid concentration in the embryo.
      Remarkably, xanthine accumulates to similar levels in the xdh mutant without
      toxicity. This is paralleled in humans, where hyperuricemia is associated with
      many diseases whereas xanthinuria is asymptomatic. Searching for the molecular
      cause of uric acid toxicity, we discovered a local defect of peroxisomes
      (glyoxysomes) mostly confined to the cotyledons of the mature embryos, which
      resulted in the accumulation of free fatty acids in dry seeds. The peroxisomal
      defect explains the developmental phenotypes of the uox mutant, drawing a novel
      link between uric acid and peroxisome function, which may be relevant beyond
      plants.

PMID- 25052715
TI  - Arabidopsis MSL10 has a regulated cell death signaling activity that is separable
      from its mechanosensitive ion channel activity.
AB  - Members of the MscS superfamily of mechanosensitive ion channels function as
      osmotic safety valves, releasing osmolytes under increased membrane tension. MscS
      homologs exhibit diverse topology and domain structure, and it has been proposed
      that the more complex members of the family might have novel regulatory
      mechanisms or molecular functions. Here, we present a study of MscS-Like (MSL)10
      from Arabidopsis thaliana that supports these ideas. High-level expression of
      MSL10-GFP in Arabidopsis induced small stature, hydrogen peroxide accumulation,
      ectopic cell death, and reactive oxygen species- and cell death-associated gene
      expression. Phosphomimetic mutations in the MSL10 N-terminal domain prevented
      these phenotypes. The phosphorylation state of MSL10 also regulated its ability
      to induce cell death when transiently expressed in Nicotiana benthamiana leaves
      but did not affect subcellular localization, assembly, or channel behavior.
      Finally, the N-terminal domain of MSL10 was sufficient to induce cell death in
      tobacco, independent of phosphorylation state. We conclude that the plant
      specific N-terminal domain of MSL10 is capable of inducing cell death, this
      activity is regulated by phosphorylation, and MSL10 has two separable activities
      one as an ion channel and one as an inducer of cell death. These findings further
      our understanding of the evolution and significance of mechanosensitive ion
      channels.

PMID- 25052717
TI  - HUA ENHANCER1 is involved in posttranscriptional regulation of positive and
      negative regulators in Arabidopsis photomorphogenesis.
AB  - Light regulates growth and developmental processes in plants via global
      transcriptome adjustment, translational control, and multilayered
      posttranslational modification of proteins. The transcriptional activation and
      repression of light-responsive genes has been well documented; however, the
      impact of posttranscriptional regulation on conveying light signals has been less
      addressed. Here, we examined whether optimal photomorphogenesis in Arabidopsis
      thaliana requires the proper biogenesis of small regulatory RNAs that play
      pivotal roles in the posttranscriptional regulation of gene expression.
      Arabidopsis carrying a mutation in HUA ENHANCER1 (HEN1), required for
      stabilization of small regulatory RNAs, showed defects in multiple aspects of
      photomorphogenic and skotomorphogenic development. HEN1 negatively regulated
      Arabidopsis photomorphogenesis. Light-activated HEN1 expression depended on the
      photoreceptors phytochrome A (phyA), phyB, cryptochrome 1 (cry1), and cry2 and
      key transcriptional regulators ELONGATED HYPOCOTYL5 (HY5) and HY5-HOMOLOG. We
      also demonstrate the involvement of the small regulatory RNAs miR157d and miR319
      in modulating the expression of a positive regulator, HY5, and negative
      regulators TEOSINTE BRANCHED1, CYCLOIDEA AND PCF family proteins, respectively,
      for optimal photomorphogenic development in Arabidopsis.

PMID- 25052718
TI  - [Uvular edema. Rare complication in anesthesia].
AB  - A uvular edema can be associated with angioedema, urticaria and anaphylaxis.
      Furthermore, it can be caused by medications, such as angiotensin-converting
      enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs and angiotensin II
      receptor antagonists. Other reasons can be cannabis or cocaine use or a traumatic
      irritation of the uvula. This article presents the case of a patient who
      underwent kidney transplantation and developed extensive edema of the uvula that
      occurred postoperatively after general anaesthesia. The case report describes the
      diagnosis and therapy of this rare disease. 

PMID- 25052716
TI  - TAA1-regulated local auxin biosynthesis in the root-apex transition zone mediates
      the aluminum-induced inhibition of root growth in Arabidopsis.
AB  - The transition zone (TZ) of the root apex is the perception site of Al toxicity.
      Here, we show that exposure of Arabidopsis thaliana roots to Al induces a
      localized enhancement of auxin signaling in the root-apex TZ that is dependent on
      TAA1, which encodes a Trp aminotransferase and regulates auxin biosynthesis. TAA1
      is specifically upregulated in the root-apex TZ in response to Al treatment, thus
      mediating local auxin biosynthesis and inhibition of root growth. The TAA1
      regulated local auxin biosynthesis in the root-apex TZ in response to Al stress
      is dependent on ethylene, as revealed by manipulating ethylene homeostasis via
      the precursor of ethylene biosynthesis 1-aminocyclopropane-1-carboxylic acid, the
      inhibitor of ethylene biosynthesis aminoethoxyvinylglycine, or mutant analysis.
      In response to Al stress, ethylene signaling locally upregulates TAA1 expression
      and thus auxin responses in the TZ and results in auxin-regulated root growth
      inhibition through a number of auxin response factors (ARFs). In particular,
      ARF10 and ARF16 are important in the regulation of cell wall modification-related
      genes. Our study suggests a mechanism underlying how environmental cues affect
      root growth plasticity through influencing local auxin biosynthesis and
      signaling.

PMID- 25052719
TI  - Nerve localization for peripheral regional anesthesia. Recommendations of the
      German Society of Anaesthesiology and Intensive Care Medicine.
AB  - The German Society of Anaesthesiology and Intensive Care Medicine (Deutsche
      Gesellschaft fur Anasthesiologie und Intensivmedizin, DGAI) established an expert
      panel to develop preliminary recommendations for nerve localization in peripheral
      regional anesthesia. Based on expert knowledge and the relatively limited data,
      the recommendations state how ultrasound and/or electrical nerve stimulation
      should be used in daily practice, and where and when local anesthetics should be
      injected. Moreover, it was defined under which conditions a peripheral nerve
      block under general anesthesia or deep sedation is applicable.Regarding the use
      of ultrasound the expert opinion was that out-of-plane and in-plane-techniques
      can be considered equal with respect to patient safety. Nevertheless, the direct
      or indirect visualization of the needle tip has to be assured. The injection of
      local anesthetics has to be visualized. Injections into nerves or those requiring
      an injection pressure should be avoided. The sole use of electrical nerve
      stimulation or ultrasound for nerve localization is still a suitable option as
      well as their combined use. To avoid accidental intraneural needle placement, an
      electrical current threshold >= 0.5 mA should be used. Moreover, it was stated
      that peripheral nerve blocks or continuous nerve block techniques under sedation
      or general anesthesia are applicable in adult patients who are unable to tolerate
      the block being performed in an awake state or have difficulty cooperating.This
      article is published in English. 

PMID- 25052720
TI  - IMRT sparing of normal tissues in locoregional treatment of breast cancer.
AB  - PURPOSE: This clinical study was designed to prospectively evaluate the acute and
      moderately-late cardiac and lung toxicities of intensity modulated radiation
      therapy delivered by helical tomotherapy (IMRT-HT) for locoregional breast
      radiation treatment including the internal mammary nodes (IMN). MATERIAL/METHODS:
      30 patients with stage III breast cancers have been accrued in this study. All
      patients received adjuvant chemotherapy. Target volumes were defined as follows:
      the PTV included breast/chest wall, axillary level II, III,
      infra/supraclavicular, IM nodes CTVs plus 3 mm margins. The heart with subunits
      and the lungs were defined as critical organs. Dose to PTV was 50 Gy in 25
      fractions. Acute toxicities were assessed every week and 2 weeks post treatment
      using the CTCAE v3.0.scale. The moderately-late toxicities were assessed
      clinically plus by cardiac myoview perfusion tests scheduled at baseline, 3 and
      12-month follow-up, as well a CT chest at the 6 month follow-up. The data
      analysis is descriptive. RESULTS: All participants completed the 5-week course of
      radiation without interruption. Skin erythema was modest and mainly grade 1-2
      between the 3rd and the 5th week of radiation treatment. Only 4/30 patients
      experienced grade 3 skin reactions, mostly seen 2 weeks post radiation. Only 5
      patients demonstrated grade 1 or 2 dyspnea, but 3 of them already had symptoms
      pre-radiation treatment. With a median follow-up of 58 (24-76) months, there have
      been infrequent moderately-late side effects. Most were grade 1 and were
      sometimes present at the baseline assessment. Cardiac myoview tests done at
      baseline and 1-year follow-up for 15 out of 18 left sided breast cancers did not
      show any abnormalities related to radiation. The 6-month follow-up chest CT-scans
      done for 25 out of 30 patients showed minimal anterior lung fibrosis for 7
      patients and were completely normal for the other 18. No locoregional recurrence
      has been recorded and the 5-year survival is 78% (95% CI: 70-97%). CONCLUSION:
      IMRT-HT for locoregional breast radiation is very well tolerated with minimal
      acute or moderately-late side effects. Cardiac and respiratory tests did not show
      any strong evidence of significant treatment related abnormalities. TRIAL
      REGISTRATION: clinicaltrials.gov: http://NCT00508352.

PMID- 25052722
TI  - Proceedings of the XXXth Congress of the European Association of Veterinary
      Anatomists, July 23-26, 2014, Cluj-Napoca, Romania.

PMID- 25052721
TI  - Commentary: Genetic influences on adolescent attachment security: an empirical
      reminder of biology and the complexities of development--a reply to Rutter
      (2014).

PMID- 25052723
TI  - Do low-income coronary artery bypass surgery patients have equal opportunity to
      access excellent quality of care and enjoy good outcome in Taiwan?
AB  - BACKGROUND: Equity is an important issue in the healthcare research field. Many
      studies have focused on the relationship between patient characteristics and
      outcomes of care. These studies, however, have seldom examined whether patients'
      characteristics affected their access to quality healthcare, which further
      affected the care outcome. The purposes of this study were to determine whether
      low-income coronary artery bypass surgery (CABG) patients receive healthcare
      services with poorer quality, and if such differences in treatment result in
      different outcomes. METHODS: A retrospective multilevel study design was
      conducted using claims data from Taiwan's universal health insurance scheme for
      2005-2008. Patients who underwent their CABG surgery between 2006 and 2008 were
      included in this study. CABG patients who were under 18 years of age or had
      unknown gender or insured classifications were excluded. Hospital and surgeon's
      performance indicators in the previous one year were used to evaluate the level
      of quality via k-means clustering algorithm. Baron and Kenny's procedures for
      mediation effect were conducted to explore the relationship among patient's
      income, quality of CABG care, and inpatient mortality. RESULTS: A total of 10,320
      patients were included in the study. The results showed that 5.65% of the low
      income patients received excellent quality of care, which was lower than that of
      patients not in the low-income group (5.65% vs.11.48%). The mortality rate of low
      income patients (12.10%) was also higher than patients not in the low-income
      group (5.25%). Also, the mortality of patients who received excellent care was
      half as low as patients receiving non-excellent care (2.63% vs. 5.68%). Finally,
      after the procedure of mediation effect testing, the results showed that the
      relationship between patient income level and CABG mortality was partially
      mediated by patterns of quality of care. CONCLUSIONS: The results of the current
      study implied that worse outcome in low-income CABG patients might be associated
      with poorer quality of received services. Health authorities should pay attention
      to this issue, and propose appropriate solutions.

PMID- 25052724
TI  - Effects of spironolactone on dialysis patients with refractory hypertension: a
      randomized controlled study.
AB  - The purpose of this study was to evaluate the effects of spironolactone on
      dialysis patients with refractory hypertension and possible adverse effects. This
      was a 12-week prospective, randomized, double-blind trial of 82 patients randomly
      assigned to 12-week treatment with 25 mg/d spironolactone or placebo as add-on
      therapy. Visits were scheduled at the start of treatment and after 12 weeks.
      Measurements of 24-hour ambulatory blood pressure (BP) monitoring and morning BP
      were performed. After 12 weeks, spironolactone significantly improved refractory
      hypertension. Average placebo-corrected morning BP was reduced by 16.7/7.6 mm Hg.
      Mean 24-hour ambulatory BP was reduced by 10.9/5.8 mm Hg. In contrast, serum
      aldosterone levels in the spironolactone group slightly increased and serum
      potassium levels insignificantly increased. This study has demonstrated that
      spironolactone (50 mg) safely and effectively reduces BP in patients with
      refractory hypertension undergoing dialysis.

PMID- 25052726
TI  - Cardiac diastolic dysfunction predicts in-hospital mortality in acute ischemic
      stroke with atrial fibrillation.
AB  - BACKGROUND: The aim of this study was to identify whether diastolic dysfunction
      predicts in-hospital death in ischemic stroke patients with atrial fibrillation.
      METHOD: We retrospectively analyzed data from enrolled patients with ischemic
      stroke patients with atrial fibrillation who presented within 24h of onset. All
      patients underwent transthoracic echocardiography to evaluate diastolic filling
      pressure estimated as the ratio of early transmitral flow velocity (E) to mitral
      annular velocity (e') within 24h of admission. We evaluated initial ischemic
      lesion volume and National Institute of Health Stroke Scale (NIHSS) score.
      RESULTS: Two hundred and sixty-six patients were enrolled. During
      hospitalization, 30 patients (11%) died. The deceased group had a higher NIHSS
      score, a higher D-dimer level, a higher creatinine level, a larger initial
      ischemic lesion volume and a higher E/e' ratio than those in the survival group.
      In a multivariate analysis, a higher E/e' ratio was an independent predictor of
      in-hospital death. The cutoff value for the E/e' ratio for prediction in-hospital
      death was 20 with the sensitivity of 75% and specificity of 86%. CONCLUSION:
      Diastolic dysfunction may be associated with in-hospital death in ischemic stroke
      patients with atrial fibrillation.

PMID- 25052727
TI  - Granulomatosis with polyangiitis presenting with pachymeningitis.
AB  - OBSERVATIONS: This case report describes a 75 year-old Caucasian male who
      initially presented with persistent daily headaches. Physical exam elicited
      multiple cranial nerve palsies. Gadolinium-enhanced brain MRI demonstrated
      pachymeningitis. Labs revealed elevated proteinase-3 antineutrophil cytoplasmic
      antibodies (PR3-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c
      ANCA), confirming a diagnosis of GPA. CONCLUSION: GPA should be considered in
      older patients presenting with persistent daily headaches and pachymeningitis.
      Contrast-enhanced brain MRI is an important diagnostic tool.

PMID- 25052728
TI  - Orthopaedic trauma surgery in low-income countries.

PMID- 25052725
TI  - From beat rate variability in induced pluripotent stem cell-derived pacemaker
      cells to heart rate variability in human subjects.
AB  - BACKGROUND: We previously reported that induced pluripotent stem cell-derived
      cardiomyocytes manifest beat rate variability (BRV) resembling heart rate
      variability (HRV) in the human sinoatrial node. We now hypothesized the BRV-HRV
      continuum originates in pacemaker cells. OBJECTIVE: To investigate whether
      cellular BRV is a source of HRV dynamics, we hypothesized 3 levels of interaction
      among different cardiomyocyte entities: (1) single pacemaker cells, (2) networks
      of electrically coupled pacemaker cells, and (3) the in situ sinoatrial node.
      METHODS: We measured BRV/HRV properties in single pacemaker cells, induced
      pluripotent stem cell-derived contracting embryoid bodies (EBs), and
      electrocardiograms from the same individual. RESULTS: Pronounced BRV/HRV was
      present at all 3 levels. The coefficient of variance of interbeat intervals and
      Poincare plot indices SD1 and SD2 for single cells were 20 times greater than
      those for EBs (P < .05) and the in situ heart (the latter two were similar; P >
      .05). We also compared BRV magnitude among single cells, small EBs (~5-10 cells),
      and larger EBs (>10 cells): BRV indices progressively increased with the decrease
      in the cell number (P < .05). Disrupting intracellular Ca(2+) handling markedly
      augmented BRV magnitude, revealing a unique bimodal firing pattern, suggesting
      that intracellular mechanisms contribute to BRV/HRV and the fractal behavior of
      heart rhythm. CONCLUSION: The decreased BRV magnitude in transitioning from the
      single cell to the EB suggests that the HRV of in situ hearts originates from the
      summation and integration of multiple cell-based oscillators. Hence, complex
      interactions among multiple pacemaker cells and intracellular Ca(2+) handling
      determine HRV in humans and cardiomyocyte networks.

PMID- 25052729
TI  - Clinical importance of lead aVR in arrhythmogenic cardiomyopathy.

PMID- 25052730
TI  - Superficial basal cell carcinoma successfully treated with ingenol mebutate gel
      0.05%.

PMID- 25052731
TI  - The role of colonoscopic screening in acromegaly revisited: review of current
      literature and practice guidelines.
AB  - INTRODUCTION: Acromegaly is a chronic, debilitating and disfiguring condition
      with a significantly increased morbidity and mortality due to cardiovascular, as
      well as respiratory complications. Patients with acromegaly are usually diagnosed
      at the age of 40, however, the duration of symptoms can vary from 5 to 10 years
      before the formal diagnosis is confirmed. Recent advances in the field of
      acromegaly have improved survival significantly. A strong association between
      acromegaly and premalignant colonic lesions and colon cancer has been
      highlighted. Furthermore, patients with acromegaly have a greater lifetime risk
      of malignant transformation and a far worse overall prognosis from colorectal
      cancer, which is now considered a major disease related complication. MATERIALS
      AND METHODS: A comprehensive search strategy was applied for the Medline/PubMed
      electronic database from its inception until April 2014. We considered all human
      research articles published in English, not classified as case report, editorial,
      comment, letter, or news. CONCLUSION: Specific recommendations for large bowel
      endoscopic screening in patients with acromegaly have been proposed. In this
      comprehensive review we discuss the current state of knowledge and evidence on
      colonoscopic screening in patients with acromegaly illustrated by a case of
      aggressive colorectal cancer presenting late in a young woman with difficult to
      control acromegaly.

PMID- 25052732
TI  - Osteogenic efficacy of bone marrow concentrate in rabbit maxillary sinus
      grafting.
AB  - Maxillary sinus grafting is required to increase bone volume in the atrophic
      posterior maxilla to facilitate dental implant placement. Grafting with
      autogenous bone (AB) is ideal, but additional bone harvesting surgery is
      unpleasant. Alternatively, bone substitutes have been used but they limit new
      bone formation. The strategy of single-visit clinical stem cell therapy using
      bone marrow aspirate concentrate (BMAC) to facilitate new bone formation has been
      proposed. This study aimed to assess bone regeneration capacity of autologous
      BMAC mixed with bovine bone mineral (BBM) in maxillary sinus grafting. Twenty
      four white New Zealand rabbits were used and their maxillary sinuses were
      randomly assigned for grafting with 4 different materials. Rates of new bone
      apposition in augmented sinuses were measured and bone histomorphometry were
      examined. Significant increase in the quantity of nucleated cells and colony
      forming unit-fibroblasts were confirmed in BMAC. Mesenchymal stem cells in BMAC
      retained their in vitro multi-differentiation capability. Higher rates of mineral
      appositions in the early period were detected in BBM + BMAC and AB than BBM
      alone, though they are not significantly different. Graft volume/tissue volumes
      in BBM and BBM + BMAC were found to be higher than those in AB and sham.

PMID- 25052733
TI  - Quality of life in treatment of mandibular fractures using closed reduction and
      maxillomandibular fixation in comparison with open reduction and internal
      fixation--a randomized prospective study.
AB  - Treatment of mandibular fractures by open reduction and internal fixation (ORIF)
      is often assumed to be superior to treatment by close reduction and
      maxillomandibular fixation (MMF) because patients managed by ORIF seem to be
      rehabilitated earlier according to functional and social aspects. This assumption
      is often from surgeon's perspective, not taking into account patient's view
      point. This study highlights a comparative assessment between ORIF and MMF from
      the patients' perspective. Fifty six patients with mandibular fractures within
      the tooth bearing areas of the mandible were prospectively studied in a
      randomized controlled pattern for postoperative Quality of Life (QoL) after ORIF
      versus MMF. Both groups were analyzed preoperatively, at 1 day, 6 and 8 weeks
      regarding their QoL using the General Oral Health Assessment Index questionnaire
      (GOHAI). No significant statistical difference was found between the groups
      regarding overall QoL. Patients managed by MMF were more affected by psychosocial
      and physical domains whereas patients managed by ORIF were more affected by the
      pain domain. The results demonstrate that the treatment affects the psychosocial,
      physical and pain domain differentially. When both treatments are possible the
      patient's should be enlightened on the advantages and disadvantages of both
      treatment modalities to guide their choice of treatment. 

PMID- 25052734
TI  - The Salmonella Typhimurium effector protein SopE transiently localizes to the
      early SCV and contributes to intracellular replication.
AB  - Salmonella enterica serovar Typhimurium (S. Tm) is a facultative intracellular
      pathogen that induces entry into non-phagocytic cells by a Type III secretion
      system (TTSS) and cognate effector proteins. Upon host cell entry, S. Tm
      expresses a second TTSS and subverts intracellular trafficking to create a
      replicative niche - the Salmonella-containing vacuole (SCV). SopE, a guanidyl
      exchange factor (GEF) for Rac1 and Cdc42, is translocated by the TTSS-1 upon host
      cell contact and promotes entry through triggering of actin-dependent ruffles.
      After host cell entry, the bulk of SopE undergoes proteasomal degradation. Here
      we show that a subfraction is however detectable on the nascent SCV membrane up
      to ~ 6 h post infection. Membrane localization of SopE and the closely related
      SopE2 differentially depend on the Rho-GTPase-binding GEF domain, and to some
      extent involves also the unstructured N-terminus. SopE localizes transiently to
      the early SCV, dependent on continuous synthesis and secretion by the TTSS-1
      during the intracellular state. Mutant strains lacking SopE or SopE2 are
      attenuated in early intracellular replication, while complementation restores
      this defect. Hence, the present study reveals an unanticipated role for SopE and
      SopE2 in establishing the Salmonella replicative niche, and further emphasizes
      the importance of entry effectors in later stages of host-cell manipulation.

PMID- 25052735
TI  - The role of donor age and gender in the success of human muscle precursor cell
      transplantation.
AB  - Autologous cell transplantation for the treatment of muscle damage is envisioned
      to involve the application of muscle precursor cells (MPCs) isolated from adult
      skeletal muscle. At the onset of trauma, these cells are recruited to proliferate
      and rebuild injured muscle fibres. However, a variety of donor-specific cues may
      directly influence the yield and quality of cells isolated from a muscle biopsy.
      In this study, we isolated human MPCs and assessed the role of donor gender and
      age on the ability of these MPCs to form functional bioengineered muscle. We
      analysed the cell yield, growth and molecular expression in vitro, and the muscle
      tissue formation and contractility of the bioengineered muscle, from cells
      isolated from men and women in three different age groups: young (20-39 years),
      adult (40-59 years) and elderly (60-80 years). Our results suggest that human
      MPCs can be successfully isolated and grown from patients of all ages and both
      genders. However, young female donors provide fast-growing cells in vitro with an
      optimum contractile output in vivo and are therefore an ideal cell source for
      muscle reconstruction. Taken together, these findings describe the donor-related
      limitations of MPC transplantation and provide insights for a straightforward and
      unbiased clinical application of these cells for muscle reconstruction. Copyright
      (c) 2014 John Wiley & Sons, Ltd.

PMID- 25052736
TI  - Physical and mechanical characterisation of 3D-printed porous titanium for
      biomedical applications.
AB  - The elastic modulus of metallic orthopaedic implants is typically 6-12 times
      greater than cortical bone, causing stress shielding: over time, bone atrophies
      through decreased mechanical strain, which can lead to fracture at the
      implantation site. Introducing pores into an implant will lower the modulus
      significantly. Three dimensional printing (3DP) is capable of producing parts
      with dual porosity features: micropores by process (residual pores from binder
      burnout) and macropores by design via a computer aided design model. Titanium was
      chosen due to its excellent biocompatibility, superior corrosion resistance,
      durability, osteointegration capability, relatively low elastic modulus, and high
      strength to weight ratio. The mechanical and physical properties of 3DP titanium
      were studied and compared to the properties of bone. The mechanical and physical
      properties were tailored by varying the binder (polyvinyl alcohol) content and
      the sintering temperature of the titanium samples. The fabricated titanium
      samples had a porosity of 32.2-53.4% and a compressive modulus of 0.86-2.48 GPa,
      within the range of cancellous bone modulus. Other physical and mechanical
      properties were investigated including fracture strength, density, fracture
      toughness, hardness and surface roughness. The correlation between the porous 3DP
      titanium-bulk modulus ratio and porosity was also quantified.

PMID- 25052737
TI  - Apatite bone cement reinforced with calcium silicate fibers.
AB  - Several research efforts have been made in the attempt to reinforce calcium
      phosphate cements (CPCs) with polymeric and carbon fibers. Due to their low
      compatibility with the cement matrix, results were not satisfactory. In this
      context, calcium silicate fibers (CaSiO3) may be an alternative material to
      overcome the main drawback of reinforced CPCs since, despite of their good
      mechanical properties, they may interact chemically with the CPC matrix. In this
      work CaSiO3 fibers, with aspect ratio of 9.6, were synthesized by a reactive
      molten salt synthesis and used as reinforcement in apatite cement. 5 wt.% of
      reinforcement addition has increased the compressive strength of the CPC by 250%
      (from 14.5 to 50.4 MPa) without preventing the cement to set. Ca and Si release
      in samples containing fibers could be explained by CaSiO3 partial hydrolysis
      which leads to a quick increase in Ca concentration and in silica gel
      precipitation. The latter may be responsible for apatite precipitation in needle
      like form during cement setting reaction. The material developed presents
      potential properties to be employed in bone repair treatment.

PMID- 25052738
TI  - [Reply to: Magnetic resonance imaging in the evaluation of patellar
      malalignment].

PMID- 25052739
TI  - DRESS syndrome due to antibiotic therapy of osteoarticular infections in
      children: two case reports.
AB  - Osteoarticular infection in children frequently occurs before 10 years of age.
      Surgical drainage is sometimes required, whereas acute osteomyelitis can be
      treated with antibiotic therapy alone. The duration of antibiotic therapy varies,
      2 weeks is sufficient for septic arthritis, whereas 6 weeks is often required for
      complicated cases. Some of these antibiotic drugs present direct complications
      with low clinical impact in certain individuals. Hypersensitivity to these drugs
      causes different reactions in children. DRESS syndrome (Drug Reaction with
      Eosinophilia and Systemic Symptoms) is a severe and potentially life-threatening
      drug reaction. It is characterised by high fever, malaise, lymphadenopathy and
      skin rash. From a clinical perspective, these symptoms can lead to an
      exacerbation of the initial infectious process for which treatment was commenced.
      The liver is the organ most often affected in DRESS syndrome associated with
      haematological changes, potentially similar to sepsis. We present two cases of
      children with osteoarticular infections who developed DRESS syndrome after
      antibiotic therapy. Both patients made a complete recovery after cessation of the
      antibiotic drugs used. 

PMID- 25052740
TI  - [Hip arthroscopy in males younger than 40 with femoroacetabular impingement:
      short-term outcomes].
AB  - INTRODUCTION AND OBJECTIVES: Femoroacetabular impingement is probably the most
      common mechanism that leads to the development of early cartilage and labral
      damage in the non-dysplastic hip. The objective was to evaluate the outcomes of
      hip arthroscopy as a treatment for femoroacetabular impingement in patients with
      high level of function. MATERIAL AND METHODS: A prospective study was performed
      on 41 patients younger than 40 years old undergoing hip arthroscopy for
      femoroacetabular impingement. Modified Harris Hip Score and HOS and IHOT
      questionnaires were used for clinical assessment. Radiological evaluation was
      made for joint space and alpha angle. RESULTS: The mean age of patients was 32.7
      years. Labrum injury was detected in 78%, and acetabular cartilage injury in 56%
      of cases. The average follow-up was 31.3 months. There was a significantly
      improvement in the mean score in the clinical questionnaires. Radiologically
      there was no change in the mean joint space, with significantly reduction to
      normal values of the alpha angle. All patients returned to sports at their pre
      injury level of function. DISCUSSION: Hip arthroscopy resulted in improvement in
      hip functional outcomes with correction of the underlying osseous deformity and
      treatment of the associated labral and cartilage pathology, with the return of
      patients to their pre-injury sports. Further follow-up is essential to confirm
      the stability of the clinical and radiological outcomes.

PMID- 25052741
TI  - To be or not to be butterfly: New mechanistic insights in the Aza-Michael
      asymmetric addition of lithium (R)-N-benzyl-N-(alpha-methylbenzyl)amide.
AB  - The asymmetric Aza-Michael addition of homochiral lithium benzylamides to
      alpha,beta-unsaturated esters represents an extended protocol to obtain
      enantioenriched beta-amino esters. An exhaustive mechanistic revision of the
      originally proposed mechanism is reported, developing a quantum
      mechanics/molecular mechanics protocol for the asymmetric Aza-Michael reaction of
      homochiral lithium benzylamides. Explicit and implicit solvent schemes were
      considered, together with a proper account of long-range dispersion forces,
      evaluated through a density functional theory benchmark of different functionals.
      Theoretical results showed that the diastereoselectivity is mainly controlled by
      the N-alpha-methylbenzyl moiety placing, deriving a Si/Re 99:1 diastereoselective
      ratio, in good agreement with reported experimental results. The main transition
      state geometries are two transition state conformers in a "V-stacked" orientation
      of the amide's phenyl rings, differing in the tetrahydrofuran molecule
      arrangement coordinated to the metal center. Extensive conformational sampling
      and quantum-level refinement give reasonable good speed/accuracy results,
      allowing this protocol to be extended to other similar Aza-Michael reaction
      systems.

PMID- 25052742
TI  - Improved statistical signal detection in pharmacovigilance by combining multiple
      strength-of-evidence aspects in vigiRank.
AB  - BACKGROUND: Detection of unknown risks with marketed medicines is key to securing
      the optimal care of individual patients and to reducing the societal burden from
      adverse drug reactions. Large collections of individual case reports remain the
      primary source of information and require effective analytics to guide clinical
      assessors towards likely drug safety signals. Disproportionality analysis is
      based solely on aggregate numbers of reports and naively disregards report
      quality and content. However, these latter features are the very fundament of the
      ensuing clinical assessment. OBJECTIVE: Our objective was to develop and evaluate
      a data-driven screening algorithm for emerging drug safety signals that accounts
      for report quality and content. METHODS: vigiRank is a predictive model for
      emerging safety signals, here implemented with shrinkage logistic regression to
      identify predictive variables and estimate their respective contributions. The
      variables considered for inclusion capture different aspects of strength of
      evidence, including quality and clinical content of individual reports, as well
      as trends in time and geographic spread. A reference set of 264 positive controls
      (historical safety signals from 2003 to 2007) and 5,280 negative controls (pairs
      of drugs and adverse events not listed in the Summary of Product Characteristics
      of that drug in 2012) was used for model fitting and evaluation; the latter used
      fivefold cross-validation to protect against over-fitting. All analyses were
      performed on a reconstructed version of VigiBase((r)) as of 31 December 2004, at
      around which time most safety signals in our reference set were emerging.
      RESULTS: The following aspects of strength of evidence were selected for
      inclusion into vigiRank: the numbers of informative and recent reports,
      respectively; disproportional reporting; the number of reports with free-text
      descriptions of the case; and the geographic spread of reporting. vigiRank
      offered a statistically significant improvement in area under the receiver
      operating characteristics curve (AUC) over screening based on the Information
      Component (IC) and raw numbers of reports, respectively (0.775 vs. 0.736 and
      0.707, cross-validated). CONCLUSIONS: Accounting for multiple aspects of strength
      of evidence has clear conceptual and empirical advantages over disproportionality
      analysis. vigiRank is a first-of-its-kind predictive model to factor in report
      quality and content in first-pass screening to better meet tomorrow's post
      marketing drug safety surveillance needs.

PMID- 25052743
TI  - Engulfing losers by winners in cancer: do cancer stem cells catch eat-me signals
      from noncancer stem cells?

PMID- 25052745
TI  - Anti-Mullerian hormone as an ovarian reserve marker in young cancer women who
      undergo ovarian tissue cryopreservation.
AB  - AIM: To evaluate if anti-Mullerian hormone (AMH) is a reliable marker of ovarian
      reserve in young women undergoing ovarian tissue cryopreservation. PATIENTS &
      METHODS: Relationships of serum AMH levels with primordial follicle density, age
      and reproductive hormones were investigated using the Pearson or Spearman
      correlation coefficient in 86 women with cancer (12-38 years) undergoing ovarian
      tissue cryopreservation. AMH variations through the menstrual cycle were assessed
      by the Kruskal-Wallis test. p < 0.05 was accepted as significant. RESULTS: AMH
      positively correlated with primordial follicle density (p = 0.03), showed great
      interindividual variability at all ages and negatively correlated with estradiol
      (p = 0.007) in the early follicular phase. AMH did not vary across the menstrual
      cycle (p = 0.415). CONCLUSION: AMH appears a valid ovarian reserve marker in
      young cancer women.

PMID- 25052746
TI  - Carboplatin plus etoposide in heavily pretreated castration-resistant prostate
      cancer patients.
AB  - AIMS: Carboplatin plus etoposide has modest efficacy in docetaxel-pretreated
      castration-resistant prostate cancer patients. We hypothesized that carboplatin
      etoposide could still exert some therapeutic activity after docetaxel,
      cabazitaxel and either abiraterone or enzalutamide. PATIENTS & METHODS: We
      enrolled 15 patients in the first step of a Phase II trial. The target sample
      size is 46 patients. The primary end point of the study was progression-free
      survival after 12 weeks. RESULTS: The median progression-free survival was 11
      weeks (range: 8-18), while median overall survival was 18 weeks (range: 12-26).
      Of seven patients with measurable disease, two had a partial response, two showed
      stable disease and the remaining three had progressive disease as the best
      radiological response. Five patients were considered progression-free after 12
      weeks, prompting continuation of the trial. CONCLUSION: Our preliminary findings
      support the hypothesis that carboplatin plus etoposide may yield some clinical
      benefit in a population of patients who failed all currently approved therapeutic
      options for prostate cancer.

PMID- 25052747
TI  - Targeted therapies in advanced renal cell carcinoma: the role of metastatic sites
      as a prognostic factor.
AB  - AIM: This retrospective study evaluates whether metastatic sites were associated
      with progression-free survival (PFS) and overall survival (OS) in patients with
      renal cell carcinoma treated with targeted therapies. PATIENTS & METHODS: In
      total, 358 patients were analyzed. RESULTS & CONCLUSION: After a median follow-up
      of 56.1 months, median PFS was 11 months and median OS was 24.2 months.
      Metastatic sites were associated with PFS: lymph nodes (HR: 1.43; 95% CI: 1.12
      1.83; p = 0.004), liver (HR: 1.41; 95% CI: 1.05-1.90; p = 0.021), bone (HR: 1.26;
      95% CI: 0.96-1.65; p = 0.091), brain (HR: 0.81; 95% CI: 0.46-1.43; p = 0.474) and
      other sites (HR: 1.07; 95% CI: 0.83-1.38; p = 0.589). Metastatic sites were
      associated with OS: lymph nodes (HR: 1.73; 95% CI: 1.31-2.29; p < 0.001), liver
      (HR: 1.71; 95% CI: 1.23-2.37; p = 0.002), bone (HR: 1.48; 95% CI: 1.10-1.98; p =
      0.009), brain (HR: 1.21; 95% CI: 0.64-2.28; p = 0.568) and other sites (HR: 1.09;
      95% CI: 0.81-1.47; p = 0.568). Patients with >2 metastatic sites had shorter PFS
      and OS. Every association was lost when introducing the Motzer score in
      regression models.

PMID- 25052748
TI  - Liposarcoma miRNA signatures identified from genome-wide miRNA expression
      profiling.
AB  - AIMS: To identify the miRNA expression profile of liposarcoma (LPS) that could
      facilitate detection of LPS, and provide the basis for further investigation of
      molecular-targeted therapeutic drugs. MATERIALS & METHODS: A real-time
      quantitative PCR assay was performed to analyze the expression of 1888 miRNAs
      from 25 LPS tumor tissue samples, 16 samples of adipose tissue adjacent to the
      tumors and 18 normal adipose tissue samples from patients with LPS. RESULTS: Ten
      dysregulated miRNAs were identified that effectively distinguished LPS tissue
      from adipose tissue and benign lipoma tissue, and LPS tumor tissues from normal
      adipose tissues in LPS patients. Furthermore, the expression profiles of miRNAs
      could also classify the subtype of LPS. CONCLUSION: The identified miRNAs appear
      to be novel biomarkers for the detection of LPS, and may contribute to an
      understanding of the mechanisms of LPS tumorigenesis and its development, and
      further elucidate the characteristics of LPS subtypes.

PMID- 25052749
TI  - Upregulation of BNIP3 mediated by ERK/HIF-1alpha pathway induces autophagy and
      contributes to anoikis resistance of hepatocellular carcinoma cells.
AB  - AIM: Acquisition of anoikis resistance is the hallmark of cancer and has been
      shown to be involved in metastasis of melignant cells. Our previous work showed
      that anoikis resistance is associated with the metastasis of hepatocellular
      carcinoma (HCC) cells. The aim of this study is to elucidate the mechanisms of
      this course. MATERIALS & METHODS: Expression of BNIP3 and HIF-1alpha at the mRNA
      and protein level in HCC cells were detected by realtime PCR and western blot,
      respectively. Autophagy activation and signaling transduction pathway were
      detected by western blot. Cell viabilities were detected by CCK8 assay and trypan
      blue exclusion assay. RESULTS: Upregulation of BNIP3 promoted the activation of
      autophagy, one type of cell survival strategy in response to external stress, by
      suppressing mTOR/S6K1 signaling system. The upregulation of BNIP3 was mediated by
      ERK/HIF-1alpha pathway, which further contributed to anoikis resistance of HCC
      cells through the mTORC1 signaling pathway. CONCLUSION: Upregulation of BNIP3
      contributs to anoikis resistance of HCC cells, and BNIP3 may serve as a novel
      therapeutic target for manipulation of cancer metastasis.

PMID- 25052750
TI  - Advances in nonsurgical treatment of benign thyroid nodules.
AB  - Ethanol ablation has traditionally been used for treatment of cystic thyroid
      nodules. Laser ablation and radiofrequency ablation were introduced later and
      used for treatment of solid thyroid nodules. However, how to select the best
      treatment modality among the different techniques has, so far, not been
      determined and causes confusion in clinical practice. Therefore, the necessity
      for a proper guideline regarding the choice of the preferable treatment modality
      has been suggested as the use of nonsurgical treatment for benign thyroid nodules
      has been increasing. This article provides an up-to-date review of nonsurgical
      treatment of benign thyroid nodules focusing on how to select the best treatment
      modality according to the composition of thyroid nodules based on the clinical
      evidence. 

PMID- 25052751
TI  - Management of acute myeloid leukemia during pregnancy.
AB  - Diagnosis of acute leukemia during pregnancy presents significant medical
      challenges. Pancytopenia, caused by bone marrow substitution with leukemic cells,
      impairs maternal and fetal health. Chemotherapeutic agents required to be
      immediately used to save the mother's life are likely to adversely affect fetal
      development and outcome, especially if administered at an early gestational
      stage. Patients diagnosed with acute leukemia during the first trimester are,
      therefore, recommended to undergo pregnancy termination. At later gestational
      stages, antileukemic therapy can be administered, although in this case, fetal
      outcome is still associated with increased incidence of growth restriction and
      loss. Special attention to the issue of future reproduction, adopting a
      personalized fertility preservation approach, is required. This article addresses
      these subjects, presenting women diagnosed with acute myeloid and acute
      promyelocytic leukemia in pregnancy. The rarity of this event, resulting in
      insufficient data, emphasizes the need for collaborative efforts to optimize
      management of this complicated clinical condition. 

PMID- 25052752
TI  - Resistance to antiangiogenic therapies.
AB  - Angiogenesis is a key process for tumoral growth, which has become a main target
      for anticancer treatments. A wide number of agents targeting both VEGF and its
      receptor have recently become standard treatments for different tumor types.
      Unfortunately, most of the tumors become resistant to these agents after few
      months of treatment. Different mechanisms of resistance to antiangiogenic drugs
      have been proposed and investigated; some agents demonstrated to be able to
      restore sensitivity to antiangiogenic drugs by blocking pathways or molecules
      involved in the resistance in preclinical models. Biomarkers for the prediction
      of response or resistance to antiangiogenic agents are under evaluation. 

PMID- 25052753
TI  - Cancers of the anal canal: diagnosis, treatment and future strategies.
AB  - Anal cancer is an uncommon cancer; however, it is rising in incidence. There is
      confusion regarding nomenclature and the distinction between anal canal cancer
      and anal margin cancer. This article discusses the modern definition, etiology
      and staging of anal canal and anal margin cancers. Modern chemotherapy and
      radiotherapy regimens are discussed, in addition to modern imaging and
      radiotherapy techniques. Future preventative strategies and potential novel
      treatments are discussed. 

PMID- 25052754
TI  - Cytokines as effectors and predictors of responses in the treatment of bladder
      cancer by bacillus Calmette-Guerin.
AB  - The most effective intravesical treatment of non-muscle-invasive bladder cancer
      is instillation of live Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG
      stimulates the release of cytokines, contributing directly or indirectly to its
      effectiveness. However, the function of specific cytokines is not well
      understood. We have undertaken a nonsystematic review of primary evidence
      regarding cytokine detection, activation and response in BCG patients. Cytokines
      IL-2, IL-8 and TNF-alpha appear to be essential for effective BCG therapy and
      nonrecurrence, while IL-10 may have an inhibitory effect on BCG responses. IL-2,
      IL-8, TRAIL and TNF-alpha are potentially predictive of response to BCG.
      Alterations in genes encoding cytokines may also affect responses. There are
      significant data showing the association of certain cytokines with successful BCG
      treatment, and which may be useful predictive markers. Isolating those cytokines
      mediating efficacy may hold the key to ameliorating BCG's side effects and
      improving efficacy and patient compliance. 

PMID- 25052755
TI  - Evolving role of tumor antigens for future melanoma therapies.
AB  - Human tumor rejection antigens recognized by T lymphocytes were first defined in
      the early 1990s and the identification of shared tumor-restricted antigens
      sparked hopes for the development of a therapeutic vaccination to treat cancer,
      including melanoma. Despite decades of intense preclinical and clinical research,
      the success of anticancer vaccines based on these antigens has been limited.
      While melanoma is a highly immunogenic tumor, the ability to prime immunity with
      vaccines has not generally translated into objective disease regression. However,
      with the development of small molecules targeting oncogenic proteins, such as
      V600-mutated BRAF, and immune checkpoint inhibitors with demonstrable long
      lasting clinical benefit, new opportunities for antigen-targeted directed
      therapies are emerging. 

PMID- 25052756
TI  - HER2 in solid tumors: more than 10 years under the microscope; where are we now?
AB  - HER2 is a well-recognized mediator of the cancerogenic process. It is
      dysregulated in a wide range of solid tumors, mainly via protein overexpression
      and/or gene amplification, thus making HER2 an attractive target for tailored
      treatment. The anti-HER2 therapy trastuzumab was approved for the treatment of
      HER2-positive metastatic breast cancer patients more than 10 years ago. Since
      then, trastuzumab and other HER2-inhibitors have been entered into clinical
      practice for the treatment of breast cancer and, more recently, have been
      approved to treat HER2-positive metastatic gastric cancers. Currently, HER2
      targeted therapies are under evaluation in other tumor types. Due to the
      relevance of proper patient selection, the accurate assessment of HER2 status is
      fundamental. This review will discuss the established knowledge and novel
      insights into the HER2 story, mainly focusing on breast, gastric and colorectal
      cancers, as well as providing a brief overview of salivary gland, bladder,
      ovarian and lung tumors. 

PMID- 25052758
TI  - Current status of circulating protein biomarkers to aid the early detection of
      lung cancer.
AB  - Considerable efforts have been undertaken to produce an effective screening
      method to reduce lung cancer mortality. Imaging tools such as low-dose computed
      tomography has shown an increase in the detection of early disease and a
      reduction in the rate of death. This screening modality has, however, several
      limitations, such as overdiagnosis and a high rate of false positives. Therefore,
      new screening methods, such as the use of circulating protein biomarkers, have
      emerged as an option that could complement imaging studies. In this review,
      current imaging techniques applied to lung cancer screening protocols are
      presented, as well as up-to-date status of circulating protein biomarker panels
      that may improve lung cancer diagnosis. Additionally, diverse statistical and
      artificial intelligence tools applied to the design and optimization of these
      panels are discussed along with the presentation of two commercially available
      blood tests recently developed to help detect lung cancer early. 

PMID- 25052757
TI  - Helicobacter pylori virulence and cancer pathogenesis.
AB  - Helicobacter pylori is human gastric pathogen that causes chronic and progressive
      gastric mucosal inflammation and is responsible for the gastric inflammation
      associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes
      reflect the interplay between host-, environmental- and bacterial-specific
      factors. Progress in understanding putative virulence factors in disease
      pathogenesis has been limited and many false leads have consumed scarce
      resources. Few in vitro-in vivo correlations or translational applications have
      proved clinically relevant. Reported virulence factor-related outcomes reflect
      differences in relative risk of disease rather than specificity for any specific
      outcome. Studies of individual virulence factor associations have provided
      conflicting results. Since virulence factors are linked, studies of groups of
      putative virulence factors are needed to provide clinically useful information.
      Here, the authors discuss the progress made in understanding the role of H.
      pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease
      pathogenesis and provide suggestions for future studies. 

PMID- 25052760
TI  - Ontogenetic development and sexual dimorphism of franciscana dolphin skull: A 3D
      geometric morphometric approach.
AB  - The aim of this work was to study the postnatal ontogenetic development of
      Pontoporia blainvillei skull, identifying major changes on shape, and relating
      them to relevant factors in the life history of the species. We analyzed a
      complete ontogenetic series (73?, 83?) with three-dimensional geometric
      morphometric techniques. Immature dolphins showed a very well-developed braincase
      and a poorly developed rostrum, and the principal postnatal changes affected the
      rostrum and the temporal fossa, both structures implied functionally to the
      feeding apparatus, thus suggesting a specialized mode for catch fast prey in P.
      blainvillei. Osseous elements associated with sound production were already well
      developed on immature dolphins, suggesting the importance of this apparatus since
      the beginning of postnatal life. Sexual dimorphism was detected on both shape and
      size variables. Females were bigger than males, in accordance with previous
      studies. Shape differences between sexes were found on the posterior part of
      premaxillaries and external bony nares (P < 0.01), suggesting that this sexual
      dimorphism is related to differences on vocalization capabilities.

PMID- 25052761
TI  - Distal oviduct and genital chamber of eriophyoids (Acariformes, Eriophyoidea):
      refined terminology and remarks on CLSM technique for studying musculature of
      mites.
AB  - The general morphology of cuticle-lined internal genitalia and oviduct is
      analyzed in intact females of the phytophagous mites, Loboquintus subsquamatus
      and Trisetacus cf bagdasariani (Acari: Eriophyoidea) using tetramethylrhodamine B
      isothiocyanate-phalloidin, three anaesthetics (magnesium sulphate, lidocaine and
      CO2-enriched water) and confocal laser scanning microscopy (CLSM). This is the
      first protocol adopted for CLSM studying musculature of mites. Revision of the
      previous terminology of eriophyoid internal genitalia from Nuzzaci and Alberti
      (Eriophyoid mites: their biology, natural enemies and control. World crop pests
      6. Elsevier, Amsterdam, pp 101-150, 1996) resulted in the refinement of the terms
      "distal oviduct", "genital chamber" and "spermatheca". Relative position of the
      elements of cuticle-lined internal genitalia is discussed and a generalized 3D
      model and animation (available on-line as supplementary material) of eriophyoid
      genital apparatus are provided. The wall of eriophyoid oviduct contains strong
      longitudinal muscles attached to the cuticle genital chamber with folded walls.
      When the egg is being extruded by contraction of the oviduct muscles, it forms
      lobes corresponding to the internal topography of the oviduct and genital
      chamber; these lobes invaginate inward from the gonopore, resulting in the
      "flower-shaped" figures rarely observed in slide-mounted mites. Gnathosomal
      muscles (cheliceral muscles and extrinsic muscles of palps) and opisthosomal
      muscles D1 of Loboquintus mites are attached to the three posterior depressions
      near the rear prodorsal shield margin. Prospects of CLSM approach for studying
      different aspects of mite morphology are briefly discussed. 

PMID- 25052762
TI  - Identification of diverse innate lymphoid cells in human decidua.
AB  - Innate lymphoid cells (ILCs) are developmentally related cells that play an
      important role in innate defenses and tissue remodeling. So far, only natural
      killer (NK) cells have been identified and functionally characterized in human
      decidua where they contribute to induction of immune suppression, neo
      angiogenesis, and tissue building/remodeling. The presence of other ILC subsets
      in human decidua has not been yet characterized. Here we identify in human
      decidua, during early pregnancy, two subsets of decidual group 3 ILC (ILC3),
      including lymphoid tissue inducer (LTi)-like cells and natural cytotoxicity
      receptors (NCRs)(+)ILC3 and interferon-(IFN)gamma-producing ILC1, different from
      NK cells. Decidual LTi-like cells produced interleukin -17 (IL-17) and tumor
      necrosis factor (TNF), while NCR(+)ILC3 released IL-22 and IL-8. Importantly,
      NCR(+)ILC3 and LTi-like cells established functional interactions with stromal
      cells. Decidual LTi-like cells differentiated into NCR(+)ILC3, whereas they
      marginally contributed to NK cell generation. Our data suggest that decidual ILC3
      may play a role in innate defenses and in vessel and tissue building, thus
      contributing to maintenance of pregnancy. 

PMID- 25052764
TI  - Role of miR-34c in ketamine-induced neurotoxicity in neonatal mice hippocampus.
AB  - Ketamine is a commonly used pediatric anesthetic, but it might affect
      development, or even induce neurotoxicity in the neonatal brain. We have used an
      in vivo neonatal mouse model to induce ketamine-related neurotoxicity in the
      hippocampus, and found that miR-34c, a microRNA associated with pathogenesis of
      Alzheimer's disease, was significantly upregulated during ketamine-induced
      hippocampal neurodegeneration. Functional assay of silencing miR-34c demonstrated
      that downregulation of miR-34c activated PKC-ERK pathway, upregulated anti
      apoptotic protein BCL2, and ameliorated ketamine-induced apoptosis in the
      hippocampus. Cognitive examination with the Morris water maze test showed that
      ketamine-induced memory impairment was significantly improved by miR-34c
      downregulation. Thus, miR-34c is important in regulating ketamine-induced
      neurotoxicity in hippocampus. 

PMID- 25052763
TI  - Targeting the HA2 subunit of influenza A virus hemagglutinin via CD40L provides
      universal protection against diverse subtypes.
AB  - The influenza viral hemagglutinin (HA) is comprised of two subunits. Current
      influenza vaccine predominantly induces neutralizing antibodies (Abs) against the
      HA1 subunit, which is constantly evolving in unpredictable fashion. The other
      subunit, HA2, however, is highly conserved but largely shielded by the HA head
      domain. Thus, enhancing immune response against HA2 could potentially elicit
      broadly inhibitory Abs. We generated a recombinant adenovirus (rAd) encoding
      secreted fusion protein, consisting of codon-optimized HA2 subunit of influenza
      A/California/7/2009(H1N1) virus fused to a trimerized form of murine CD40L, and
      determined its ability of inducing protective immunity upon intranasal
      administration. We found that mice immunized with this recombinant viral vaccine
      were completely protected against lethal challenge with divergent influenza A
      virus subtypes including H1N1, H3N2, and H9N2. Codon-optimization of HA2 as well
      as the use of CD40L as a targeting ligand/molecular adjuvant were indispensable
      to enhance HA2-specific mucosal IgA and serum IgG levels. Moreover, induction of
      HA2-specific T-cell responses was dependent on CD40L, as rAd secreting HA2
      subunit without CD40L failed to induce any significant levels of T-cell
      cytokines. Finally, sera obtained from immunized mice were capable of inhibiting
      13 subtypes of influenza A viruses in vitro. These results provide proof of
      concept for a prototype HA2-based universal influenza vaccine. 

PMID- 25052765
TI  - The effectiveness of nonsteroidal anti-inflammatory agents in the treatment of
      pelvic inflammatory disease: a systematic review.
AB  - BACKGROUND: Pelvic inflammatory disease (PID) is the result of infection
      ascending through the endocervix to the uterus and fallopian tubes. Inflammation
      driven by infected host cells appears to be central to the development of tissue
      damage and associated reproductive complications. Nonsteroidal anti-inflammatory
      agents (NSAIDs) therefore have the potential to reduce the sequelae associated
      with pelvic infection. METHODS: A search of four electronic reference databases,
      an internet search for relevant grey literature and a review of the
      bibliographies of identified publications was used to identify studies evaluating
      NSAIDs in the management of PID. A predefined search strategy was used to
      identify studies that included women with PID aged over 16 and diagnosed after
      1980. Randomized controlled trials, nonrandomized controlled trials, and cohort
      studies with comparison group data were included without language restriction.
      Two reviewers independently assessed the studies against agreed criteria and
      extracted relevant data using a standardized pro forma. A meta-analysis to
      calculate the relative risk associated with NSAID use was planned if appropriate.
      RESULTS: Forty-three studies were identified. After reviewing abstracts or full
      texts, two randomized controlled trials were found to meet the selection criteria
      for inclusion. The use of NSAIDs was reported to improve tubal patency, reduce
      pelvic adhesions and reduce suprapubic pain but the studies were of poor quality
      with a high risk of bias. Meta-analysis of the data was not performed.
      CONCLUSIONS: Insufficient data is available to support or refute the efficacy of
      NSAIDs in the prevention of short or long-term complications of PID.

PMID- 25052766
TI  - Hypoxia represses microRNA biogenesis proteins in breast cancer cells.
AB  - BACKGROUND: Cancers are commonly characterised by hypoxia and also by global
      reductions in the levels of mature microRNAs. We have examined the hypothesis
      that hypoxia might mediate this reduction through repressive effects on microRNA
      biogenesis proteins. METHODS: Breast cancer cell lines were exposed to hypoxia
      and manipulations of hypoxia inducible factor (HIF) and HIF hydroxylase activity.
      The effects of hypoxia on the mRNA and protein levels of enzymes involved in
      microRNA biogenesis (Dicer, Drosha, TARPB2, DCGR8, XPO5) was determined by RT PCR
      and immunoblotting. The effect of hypoxia on microRNAs was determined with
      microarray studies, RT PCR and reporter assays. RESULTS: In breast cancer lines
      there was significant reduction of Dicer mRNA and protein levels in cells exposed
      to hypoxia. This effect was independent of HIF but dependent on the HIF
      hydroxylase PHD2 and was partly mediated by feedback effects via microRNAs.
      Furthermore, several other proteins with critical roles in microRNA biogenesis
      (Drosha, TARBP2 and DCGR8) also showed significant and co-ordinated repression
      under hypoxic conditions. Despite these substantial alterations no, or modest,
      changes were observed in mature microRNA production. CONCLUSION: These
      observations provide further and important interfaces between oxygen availability
      and gene expression and a potential mechanistic explanation for the reduced
      levels of microRNAs observed in some cancers. They provide further support for
      the existence of feedback mechanisms in the regulation of the microRNA biogenesis
      pathway and the relative stability of microRNAs.

PMID- 25052767
TI  - Comparative evaluation of three-dimensional Gd-EOB-DTPA-enhanced MR fusion
      imaging with CT fusion imaging in the assessment of treatment effect of
      radiofrequency ablation of hepatocellular carcinoma.
AB  - PURPOSE: To assess the feasibility of fusion of pre- and post-ablation gadolinium
      ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance
      imaging (Gd-EOB-DTPA-MRI) to evaluate the effects of radiofrequency ablation
      (RFA) of hepatocellular carcinoma (HCC), compared with similarly fused CT images
      PATIENTS AND METHODS: This retrospective study included 67 patients with 92 HCCs
      treated with RFA. Fusion images of pre- and post-RFA dynamic CT, and pre- and
      post-RFA Gd-EOB-DTPA-MRI were created, using a rigid registration method. The
      minimal ablative margin measured on fusion imaging was categorized into three
      groups: (1) tumor protruding outside the ablation zone boundary, (2) ablative
      margin 0-<5.0 mm beyond the tumor boundary, and (3) ablative margin >=5.0 mm
      beyond the tumor boundary. The categorization of minimal ablative margins was
      compared between CT and MR fusion images. RESULTS: In 57 (62.0%) HCCs, treatment
      evaluation was possible both on CT and MR fusion images, and the overall
      agreement between them for the categorization of minimal ablative margin was good
      (kappa coefficient = 0.676, P < 0.01). MR fusion imaging enabled treatment
      evaluation in a significantly larger number of HCCs than CT fusion imaging (86/92
      [93.5%] vs. 62/92 [67.4%], P < 0.05). CONCLUSIONS: Fusion of pre- and post
      ablation Gd-EOB-DTPA-MRI is feasible for treatment evaluation after RFA. It may
      enable accurate treatment evaluation in cases where CT fusion imaging is not
      helpful.

PMID- 25052768
TI  - A look at statin cost-effectiveness in view of the 2013 ACC/AHA cholesterol
      management guidelines.
AB  - The 2013 cholesterol management guidelines presented a major shift in
      recommendations on which patients at risk of cardiovascular disease should be
      treated and how to treat them. Implementation of the guidelines is estimated to
      increase substantially the number of people who would be eligible for statin
      therapy. As the medical community considers the broad population impact of the
      new cholesterol guidelines, the issue of cost-effectiveness plays a role. This
      review covers the basic fundamentals of cost-effectiveness analysis and
      summarizes the key cost-effectiveness studies that relate to the new cholesterol
      guidelines. 

PMID- 25052770
TI  - Evaluation of a clinical needs assessment and exploration of the associated
      supports for students with a disability in clinical practice: part 2.
AB  - Engagement and successful completion of nursing and midwifery programmes may be
      predicated on the identification and implementation of reasonable accommodations
      to facilitate clinical learning for students with a disability. This qualitative
      study aims to evaluate a clinical needs assessment for students with a disability
      and explore their experiences of support in clinical practice. A purposive sample
      of year one undergraduate students was used. Four students consented to
      participate and undertook an individual interview. Their disabilities were
      categorised as specific learning disability (dyslexia) (n = 3) and mental health
      (n = 1). Data analysis revealed two main themes 'students' experiences of
      disclosure' and 'receiving support'. Findings revealed that all students
      disclosed on placement, however, the extent of disclosure was influenced by
      personal and environmental factors. Students used the clinical needs assessment
      to highlight accommodations to clinical staff on placement. Issues of concern
      that arose, included communication between all key stakeholders, negative staff
      attitudes and the need to improve the provision of accommodations. This
      preliminary evaluation indicates that the Clinical Needs Assessment bridges the
      gap in provision of student support between higher education and healthcare
      institutions. Findings suggest that competence based needs assessments can
      identify individualised reasonable accommodations for students undertaking
      clinical placements.

PMID- 25052771
TI  - Computer-based quantification of the Achilles tendon thickness in sequential B
      mode ultrasound images: a study of feasibility and reliability.
AB  - INTRODUCTION: Assessment of the Achilles tendon thickness (ATT) using B-mode
      ultrasound is a common technique for clinical evaluation of chronic mid-part
      tendinosis. Currently used image-based assessment is limited by relatively high
      inter- and intra-observer variability. In this study, it was tested whether a new
      sequence-based automated assessment of ATT provides more reliable and
      reproducible results than the standard image-based procedure. MATERIALS AND
      METHODS: A total of 118 non-operated tendons of 59 healthy subjects (44, range 28
      50 years) were analysed using an automated image based as well as a newly
      developed automated sequence-based method. Correlation and agreement of both
      methods were evaluated. The root mean square deviation (RMSD) and a Bland-Altman
      analysis were performed to highlight observer (n = 18 tendons) as well as reader
      (n = 40 tendons) dependent variabilities of both methods. RESULTS: A strong
      correlation was found between image and sequence-based ATT assessment (p = 0.92).
      The Bland-Altman analysis showed a good agreement between both methods (mean
      difference 0.0018, 95 % CI: -0.046; 0.05). In repetitive examinations, sequence
      based analysis showed a significant reduction concerning reader- and observer
      dependent variability compared to image-based assessment. The RMSD for repetitive
      sequence-based measurements was approximately 0.3 mm (compared to 0.6 mm for
      image-based measurement), respectively. CONCLUSIONS: The study shows sequence
      based automated assessment of ATT being clearly superior to the standard image
      based procedure. The new method provides a clear reduction of reader as well as
      observer-dependent variability. Due to the decreased scattering of measurement
      data sequence-based measurement seems especially valuable for quantification of
      small tendon thickness changes such as exercise-induced hypertrophy.

PMID- 25052769
TI  - Living the PCSK9 adventure: from the identification of a new gene in familial
      hypercholesterolemia towards a potential new class of anticholesterol drugs.
AB  - A decade after our discovery of the involvement of proprotein convertase
      subtilisin/kexin type 9 (PCSK9) in cholesterol metabolism through the
      identification of the first mutations leading to hypercholesterolemia, PCSK9 has
      become one of the most promising targets in cholesterol and cardiovascular
      diseases. This challenging work in the genetics of hypercholesterolemia paved the
      way for a plethora of studies around the world allowing the characterization of
      PCSK9, its expression, its impact on reducing the abundance of LDL receptor, and
      the identification of loss-of-function mutations in hypocholesterolemia. We
      highlight the different steps of this adventure and review the published clinical
      trials especially those with the anti-PCSK9 antibodies evolocumab (AMG 145) and
      alirocumab (SAR236553/REGN727), which are in phase III trials. The promising
      results in lowering LDL cholesterol levels raise hope that the PCSK9 adventure
      will lead, after the large and long-term ongoing phase III studies evaluating
      efficacy and safety, to a new anticholesterol pharmacological class. 

PMID- 25052772
TI  - Tibial tubercle osteotomy in septic revision total knee arthroplasty.
AB  - PURPOSE: The incidence of revision knee arthroplasty for infection is increasing
      and the required surgical approach for the revision is a challenge for surgeons.
      Extensile approaches are frequently used when it is impossible to evert the
      extensor mechanism. The aim of this paper is to report our experience with tibial
      tubercle osteotomy (TTO) and the functional results in patients who underwent a
      two-stage revision due to prosthesis infection. METHODS: Twenty-six patients
      underwent a TTO as a surgical approach in the second stage of revision for
      infection. The patients were clinically assessed by means of functional scales
      (the Knee Society Score and WOMAC) and X-rays. RESULTS: The TTO healed without
      complications in 22 patients (84.6%) and the average length of follow-up was 3.4
      years. Non-union was observed in two patients. One patient presented an extension
      lag of 5 degrees . A total of 23 patients (88.4%) were free from infection.
      Twenty-five patients (96.1%) had better scores on the Knee Society Score and
      WOMAC after the procedure. CONCLUSIONS: In patients undergoing the second stage
      of revision total knee arthroplasty for infection, the TTO approach provides a
      large operating field. This enables surgeons to withdraw spacers and position new
      implants without damaging the extensor mechanism of the knee or altering the
      postoperative rehabilitation process. The complications that have been reported
      as a result of this procedure could be reduced by performing a meticulous
      surgical technique. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

PMID- 25052773
TI  - Ultrasound guidance during embryo transfer: a systematic review and meta-analysis
      of randomized controlled trials.
AB  - OBJECTIVES: To summarize the current evidence on the effect of using ultrasound
      (US) guidance during embryo transfer (ET). METHODS: In this systematic review, we
      included randomized controlled trials examining the effect of the use of US
      guidance during ET; data from studies using the same catheter type in study arms
      were not pooled with the results from studies that used different catheter types.
      RESULTS: Twenty-one studies were included in the quantitative analysis: 18
      compared 'US guidance' with 'clinical touch', of which one was subsequently
      excluded from the quantitative meta-analysis owing to a lack of available data,
      three studies compared transvaginal US guidance with transabdominal US guidance,
      and one study compared 'hysterosonometry before ET' with US guidance. Comparison
      of the use of US guidance with clinical touch, in studies that used the same
      catheter type in the study arms, indicated a benefit of using US guidance during
      ET on the rates of live birth (relative risk (RR), 1.48 (95% CI, 1.16-1.87)),
      based on two studies involving 888 women with moderate-quality evidence, and on
      the rates of clinical pregnancy (RR, 1.32 (95% CI, 1.18-1.46)), based on 13
      studies involving 3641 women with high-quality evidence. However, when comparing
      the use of US guidance with clinical touch in studies that used different
      catheter types, the results suggest that using US guidance during ET has no
      effect on the rates of reproductive outcome: live birth (RR, 0.99 (95% CI, 0.83
      1.19)), based on one study involving 1649 women with moderate-quality evidence;
      clinical pregnancy (RR, 1.04 (95% CI, 0.89-1.21)), based on five studies
      involving 2949 women with moderate-quality evidence. The estimates for the rate
      of miscarriage and for the other identified comparisons were imprecise.
      CONCLUSIONS: The available evidence suggests that there is a benefit of using US
      guidance during ET. However, both US-guided transfer and clinical touch should be
      considered acceptable, as the benefit of US is not large and should be balanced
      against the increased cost and need to change the catheter type. More studies are
      required before conclusions can be drawn regarding the effect of other techniques
      on reproductive outcome.

PMID- 25052776
TI  - IgE antibodies specific to alpha-gal: an example of clinically relevant cross
      reactive anti-carbohydrate antibodies.

PMID- 25052774
TI  - Xq26.1-26.2 gain identified on array comparative genomic hybridization in
      bilateral periventricular nodular heterotopia with overlying polymicrogyria.
AB  - Periventricular nodular heterotopia (PNH) with overlying polymicrogyria (PMG) is
      a recently described, developmental brain malformation; however, the causative
      genes of this malformation have not yet been identified. We report on a 5-year
      old Japanese male with bilateral PNH with overlying PMG. He had mild intellectual
      disability, distinctive facial features, short stature, and microcephaly, with
      cardiac disorders. No mutation was identified in Sanger sequences for FLNA and
      ARFGEF2; however, array comparative genomic hybridization revealed an
      approximately 0.8Mb gain at Xq26.1-26.2, which included three genes: IGSF1,
      OR13H1, and FIRRE. We identified the same 3-copy gain in his mother; despite
      identifying the same abnormality in the mother, it must still be considered as a
      possible cause for the abnormalities, as X-inactivation in the mother could have
      led to her not expressing the same phenotype. This case may provide important
      clues for identifying the genes responsible and help in the understanding of the
      pathogenesis of this disorder. 

PMID- 25052778
TI  - Microarray immobilization of biomolecules using a fast trans-cyclooctene (TCO)
      tetrazine reaction.
AB  - By anchoring 1,2,4,5-tetrazine-containing biomolecules onto trans-cyclooctene
      (TCO)-functionalized slides, a site-specific microarray immobilization approach
      is described in this study. Compared with existing immobilization methods, our
      approach offers several distinctive features, including fast kinetics and high
      chemoselectivity. 

PMID- 25052779
TI  - Further definition on the multiple partner choice arena: a potential animal model
      for the study of premature ejaculation.
AB  - INTRODUCTION: The multiple partner choice arena (MPCA) is an experimental setup
      in which male rats display a significant shortening of ejaculation latency, which
      is the main characteristic of premature ejaculation (PE) in men. Thus, the MPCA
      is a potential animal model for PE. AIM: In this study, we further analyze
      whether the features of the MPCA satisfy the validity criteria for it to be
      considered an animal model as well as the possible participation of the
      serotoninergic system in the faster ejaculation exhibited by male rats in the
      MPCA. METHODS: In Experiment 1, male rats were tested in a standard arena to
      assess their sexual behavior, then were assessed 1 week later in the MPCA.
      Another group was first tested in the MPCA, then in a standard arena. In
      Experiment 2, male rats divided into two groups were treated daily with WAY
      100635 (5-HT(1A) antagonist) or vehicle for 15 days. In each group, half of the
      subjects were tested in a standard arena and half were tested in the MPCA on days
      1, 8, and 15 of treatment. MAIN OUTCOME MEASURES: Number of intromissions and
      intromission and ejaculation latencies were the main outcome measures. RESULTS:
      In Experiment 1, males tested in the MPCA ejaculated significantly faster,
      regardless of the order in which they were evaluated in both arenas. In
      Experiment 2, the administration of WAY-100635 increased intromission and
      ejaculation latencies, and the number of intromissions in the MPCA. CONCLUSIONS:
      The results obtained in the MPCA support its use as an animal model for PE
      evaluation.

PMID- 25052780
TI  - Transport mechanism and regulatory properties of the human amino acid transporter
      ASCT2 (SLC1A5).
AB  - The kinetic mechanism of the transport catalyzed by the human glutamine/neutral
      amino acid transporter hASCT2 over-expressed in P. pastoris was determined in
      proteoliposomes by pseudo-bi-substrate kinetic analysis of the Na(+)
      glutamineex/glutaminein transport reaction. A random simultaneous mechanism
      resulted from the experimental analysis. Purified functional hASCT2 was
      chemically cross-linked to a stable dimeric form. The oligomeric structure
      correlated well with the kinetic mechanism of transport. Half-saturation
      constants (Km) of the transporter for the other substrates Ala, Ser, Asn and Thr
      were measured both on the external and internal side. External Km were much lower
      than the internal ones confirming the asymmetry of the transporter. The electric
      nature of the transport reaction was determined imposing a negative inside
      membrane potential generated by K(+) gradients in the presence of valinomycin.
      The transport reaction resulted to be electrogenic and the electrogenicity
      originated from external Na(+). Internal Na(+) exerted a stimulatory effect on
      the transport activity which could be explained by a regulatory, not a counter
      transport, effect. Native and deglycosylated hASCT2 extracted from HeLa showed
      the same transport features demonstrating that the glycosyl moiety has no role in
      transport function. Both in vitro and in vivo interactions of hASCT2 with the
      scaffold protein PDZK1 were revealed. 

PMID- 25052781
TI  - Cysteamine, a pro-BDNF drug, as an adjunctive treatment for schizophrenia.

PMID- 25052783
TI  - Effect of early intervention on premature infants' general movements.
AB  - This study is to investigate the characteristics of premature infants' general
      movements (GMs) and the effect of early intervention on their GMs. METHODS: The
      survey was carried among 285 premature infants. (1) Before intervention, the
      correlation between the gestational age/ birth weight and the GMs was evaluated.
      (2) The cases were divided into early intervention group (n=145) and control
      group (n=140), each group was divided into <32 weeks, 32-34 weeks and >34 weeks
      group according to gestational age. The early intervention was begun at the 3rd
      day after birth to 54th week gestational age. The rate of GMs among each group
      was compared after intervention. RESULTS: (1) Before intervention, gestational
      age/birth weight was negatively correlated with the rate of cramped-synchronized
      (CS) (r=-0.988, r=-0.95, p<0.01), while no correlation with the rate of poor
      repertoire (PR) (r=0.122, r=0.168, p>0.05). (2) After intervention, for the
      writhing movement, there was no significant difference (chi2=0.509, 1.401, 0.519,
      p>0.05) between the early intervention group and the control group. Nevertheless,
      for the fidgety movement, there was significant difference (chi2=7.921,
      chi2=5.763, p<0.05) between the two groups, especially in <32 weeks group
      (chi2=5.578, 4.067 p<0.05) and in >34 weeks group (chi2=5.757, p<0.05).
      CONCLUSIONS: (1) It shows that the lower birth weight or the younger delivery
      gestational age, the more abnormal GMs in premature infants. (2) Early
      intervention could improve the fidgety movements of premature infant.

PMID- 25052782
TI  - Emotion recognition deficits in schizophrenia-spectrum disorders and psychotic
      bipolar disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate
      Phenotypes (B-SNIP) study.
AB  - BACKGROUND: Difficulty recognizing facial emotions is an important social
      cognitive deficit associated with psychotic disorders. It also may reflect a
      familial risk for psychosis in schizophrenia-spectrum disorders and bipolar
      disorder. OBJECTIVE: The objectives of this study from the Bipolar-Schizophrenia
      Network on Intermediate Phenotypes (B-SNIP) consortium were to: 1) compare
      emotion recognition deficits in schizophrenia, schizoaffective disorder and
      bipolar disorder with psychosis, 2) determine the familiality of emotion
      recognition deficits across these disorders, and 3) evaluate emotion recognition
      deficits in nonpsychotic relatives with and without elevated Cluster A and
      Cluster B personality disorder traits. METHOD: Participants included probands
      with schizophrenia (n=297), schizoaffective disorder (depressed type, n=61;
      bipolar type, n=69), bipolar disorder with psychosis (n=248), their first-degree
      relatives (n=332, n=69, n=154, and n=286, respectively) and healthy controls
      (n=380). All participants completed the Penn Emotion Recognition Test, a
      standardized measure of facial emotion recognition assessing four basic emotions
      (happiness, sadness, anger and fear) and neutral expressions (no emotion).
      RESULTS: Compared to controls, emotion recognition deficits among probands
      increased progressively from bipolar disorder to schizoaffective disorder to
      schizophrenia. Proband and relative groups showed similar deficits perceiving
      angry and neutral faces, whereas deficits on fearful, happy and sad faces were
      primarily isolated to schizophrenia probands. Even non-psychotic relatives
      without elevated Cluster A or Cluster B personality disorder traits showed
      deficits on neutral and angry faces. Emotion recognition ability was moderately
      familial only in schizophrenia families. CONCLUSIONS: Emotion recognition
      deficits are prominent but somewhat different across psychotic disorders. These
      deficits are reflected to a lesser extent in relatives, particularly on angry and
      neutral faces. Deficits were evident in non-psychotic relatives even without
      elevated personality disorder traits. Deficits in facial emotion recognition may
      reflect an important social-cognitive deficit in patients with psychotic
      disorders.

PMID- 25052784
TI  - Cognitive-behavioral therapy in depressed primary care patients with co-occurring
      problematic alcohol use: effect of telephone-administered vs. face-to-face
      treatment-a secondary analysis.
AB  - This secondary analysis of a larger study compared adherence to telephone
      administered cognitive-behavioral therapy (T-CBT) vs. face-to-face CBT and
      depression outcomes in depressed primary care patients with co-occurring
      problematic alcohol use. To our knowledge, T-CBT has never been directly compared
      to face-to-face CBT in such a sample of primary care patients. Participants were
      randomized in a 1:1 ratio to face-to-face CBT or T-CBT for depression.
      Participants receiving T-CBT (n = 50) and face-to-face CBT (n = 53) were compared
      at baseline, end of treatment (week 18), and three-month and six-month follow
      ups. Face-to-face CBT and T-CBT groups did not significantly differ in age, sex,
      ethnicity, marital status, educational level, severity of depression,
      antidepressant use, and total score on the Alcohol Use Disorders Identification
      Test. Face-to-face CBT and T-CBT groups were similar on all treatment adherence
      outcomes and depression outcomes at all time points. T-CBT and face-to-face CBT
      had similar treatment adherence and efficacy for the treatment of depression in
      depressed primary care patients with co-occurring problematic alcohol use. When
      targeting patients who might have difficulties in accessing care, primary care
      clinicians may consider both types of CBT delivery when treating depression in
      patients with co-occurring problematic alcohol use.

PMID- 25052785
TI  - Social support network characteristics of incarcerated women with co-occurring
      major depressive and substance use disorders.
AB  - The nature of social support available to incarcerated women is not well
      understood, particularly among women at high risk of negative outcomes, including
      women dually diagnosed with Major Depressive Disorder and a Substance Use
      Disorder (MDD-SUD). Descriptive statistics and paired-tests were conducted on 60
      incarcerated MDD-SUD women receiving in-prison substance use and depression
      treatments to characterize the women's social networks, including the strength of
      support, network characteristics, and types of support provided as well as to
      determine what aspects of social support may be amenable to change during
      incarceration and post-release. Study results showed that, on average, women
      perceived they had moderately supportive individuals in their lives, although
      more than a quarter of the sample could not identify any regular supporters in
      their network at baseline. During incarceration, women's social networks
      significantly increased in general supportiveness, and decreased in network size
      and percentage of substance users in their networks. Participants maintained
      positive social support gains post-release in most areas while also significantly
      increasing the size of their support network post-release. Findings suggest that
      there are aspects of incarcerated MDD-SUD women's social networks that are
      amenable to change during incarceration and post-release and provide insight into
      treatment targets for this vulnerable population.

PMID- 25052787
TI  - Patterns of abstinence or continued drug use among methadone maintenance patients
      and their relation to treatment retention.
AB  - The efficacy and effectiveness of methadone maintenance treatment (MMT) in the
      medical management of opioid addiction has been well-established, but treatment
      outcomes are compromised by the continued use of licit and illicit drugs during
      MMT. The present study examined the relationship between in-treatment illicit
      drug use and retention and dropout of 604 MMT patients in Washington, D.C. Sixty
      eight percent of patients did not test positive for an unprescribed drug during
      the study period. Of patients who tested positive for an illicit drug during the
      baseline period, 55% tested positive for cocaine, 44% for opiates, 23% for THC,
      20% for benzodiazepines, 7% for PCP, and 4% for amphetamines. Those testing
      positive were three times more likely to leave treatment than those who did not
      test positive. Testing positive for one drug doubled the rate of attrition;
      testing positive for multiple drugs quadrupled the risk of attrition. Non
      prescribed opioid or benzodiazepine use was a predictor of MMT dropout, but
      prescribed opioid or benzodiazepine use was not. Continued illicit drug use poses
      significant risk for subsequent premature termination of MMT. Assertive clinical
      management of continued illicit drug use could provide mechanisms to enhance MMT
      retention and long-term recovery outcomes.

PMID- 25052786
TI  - Social adjustment of women with and without a substance-abusing partner.
AB  - Little normative information is available about the psychosocial functioning of
      women who have a substance-abusing intimate partner. This study examined whether
      the social adjustment of women who indicate that they have a substance-abusing
      partner (n=69) is compromised relative to that of women who indicate that their
      partner does not abuse substances (n=68). Women with a substance-abusing partner
      reported compromised social adjustment relative to a comparison sample both
      overall and in five of six life domains (work, social/leisure, primary
      relationship, parental, family). Results suggest the potential benefit of
      expanding the focus of research and treatment to include effects and outcomes for
      these women and to influence treatment-related policy.

PMID- 25052788
TI  - Understanding prolonged cessation from heroin use: findings from a community
      based sample.
AB  - BACKGROUND: There is abundant literature describing heroin initiation, co
      morbidities, and treatment. Few studies focus on cessation, examining the factors
      that motivate and facilitate it. METHODS: The CHANGE study utilized mixed methods
      to investigate heroin cessation among low-income New York City participants. This
      paper describes findings from qualitative interviews with 20 former and 11
      current heroin users. Interviews focused on background and current activities,
      supports, drug history, cessation attempts, and motivators and facilitators to
      cessation. RESULTS: Participants found motivation for cessation in improved
      quality of life, relationships, and fear of illness, incarceration and/or death.
      Sustained cessation required some combination of treatment, strategic avoidance
      of triggers, and engagement in alternative activities, including support groups,
      exercise, and faith-based practice. Several reported that progress toward goals
      served as motivators that increased confidence and facilitated cessation.
      Ultimatums were key motivators for some participants. Beyond that, they could not
      articulate factors that distinguished successful from unsuccessful cessation
      attempts, although data suggest that those who were successful could describe
      more individualized and concrete-rather than general-motivators and strategies.
      CONCLUSIONS: Our findings indicate that cessation may be facilitated by
      multifaceted and individualized strategies, suggesting a need for personal and
      comprehensive approaches to treatment.

PMID- 25052789
TI  - Mood, mood regulation, and frontal systems functioning in current smokers, long
      term abstinent ex-smokers, and never-smokers.
AB  - Indices of mood, mood regulation, and executive functioning were examined in 61
      current smokers who have smoked daily for at least one year, 36 ex-smokers who
      had not smoked a cigarette for at least one year, and 86 never-smokers. All
      participants completed the following measures online: Depression Anxiety Stress
      Scales (DASS-21), the Negative Mood Regulation (NMR) scale, the Frontal Systems
      Behavior Scale (FrSBe), the Fagerstrom Test for Cigarette Dependence (FTCD), and
      the Alcohol Use Disorders Identification Test (AUDIT). Multivariate analysis of
      variance (MANOVA) followed by Tukey post-hoc tests revealed significant
      differences (p < .01) such that current smokers indicated worse functioning than
      both ex-smokers and never-smokers on DASS, NMR, and FrSBe, as well as heavier
      drinking as measured by AUDIT. These differences remained significant even after
      controlling for AUDIT scores. Results most plausibly reflect a return to pre
      smoking baseline brain function in long-term abstinent ex-smokers.

PMID- 25052790
TI  - Psychometric properties of the Turkish versions of the Drug Use Disorders
      Identification Test (DUDIT) and the Drug Abuse Screening Test (DAST-10) in the
      prison setting.
AB  - The aim of this study was to evaluate psychometric properties of the Drug Use
      Disorders Identification Test (DUDIT) and the Drug Abuse Screening Test (DAST-10)
      in prisoners with (n = 124) or without (n = 78) drug use disorder. Participants
      were evaluated with the DUDIT, the DAST-10, and the Addiction Profile Index-Short
      (API-S). The DUDIT and the DAST-10 were found to be psychometrically sound drug
      abuse screening measures with high convergent validity when compared with each
      other (r = 0.86), and API-S (r = 0.88 and r = 0.84, respectively), and to have a
      Cronbach's alpha of 0.93 and 0.87, respectively. In addition, a single component
      accounted for 58.28% of total variance for DUDIT, whereas this was 47.10% for
      DAST-10. The DUDIT had sensitivity and specificity scores of 0.95 and 0.79,
      respectively, when using the optimal cut-off score of 10, whereas these scores
      were 0.88 and 0.74 for the DAST-10 when using the optimal cut-off score of 4.
      Additionally, both the DUDIT and the DAST-10 showed good discriminant validity as
      they differentiated prisoners with drug use disorder from those without. Findings
      support the Turkish versions of both the DUDIT and the DAST-10 as reliable and
      valid drug abuse screening instruments that measure unidimensional constructs.

PMID- 25052791
TI  - Not-so-clean fun: a profile of bath salt users among a college sample in the
      United States.
AB  - This research examines the characteristics of users of synthetic stimulants
      marketed as "bath salts." Synthetic stimulants such as MDPV (3,4
      Methylenedioxypyrovalerone), Mephedrone (4-Methylmethcathinone), and Methylone
      (3,4-Methylenedioxymethcathinone) are often contained in products sold at
      convenience stores and over the Internet in the United States. Despite the recent
      legal action banning these types of synthetic stimulants, little is known about
      the characteristics of the users of these substances. This research provides a
      profile of bath salt users in the United States among an emerging adult
      population. A self-report survey instrument was administered to 2,349 students at
      a large university in the southeastern United States. Respondents indicated
      whether they had used synthetic stimulants and reported demographic
      characteristics. Results indicated that users of bath salts were more likely to
      be male, Hispanic or Native American, student athletes, employed, identify as a
      members of the LGBT community, and users of other substances.

PMID- 25052792
TI  - The prevalence, intensity, and assessment of craving for MDMA/ecstasy in
      recreational users.
AB  - This study evaluated the prevalence, intensity, and correlates of craving for
      MDMA/ecstasy among recreational users employing a new multi-item, self-report
      questionnaire reflecting experiences of desire, intention to use, and anticipated
      loss of control. Using a web-based data collection procedure, we recruited
      MDMA/ecstasy users (n = 240) to rate their agreement with eight craving
      statements immediately before and immediately following 90 seconds of exposure to
      either ecstasy-related or control stimuli. Participants then completed
      questionnaires to measure ecstasy refusal self-efficacy, passionate engagement in
      ecstasy use, substance use history, and demographic information. Fifty percent of
      participants indicated some level of agreement with at least two (out of eight)
      statements indicative of craving and 30% agreed at some level with six or more
      such statements. The questionnaire used to assess craving was internally
      consistent, unidimensional, and had excellent one-week test-retest reliability.
      Craving scores varied as a function of both cue exposure and frequency of ecstasy
      use, and were significantly associated with ecstasy-related attitudes.
      Recreational users of MDMA/ecstasy endorse some experiences indicative of craving
      for this drug, even though only a minority report intense craving following
      explicit cue exposure.

PMID- 25052793
TI  - Buprenorphine prescription compliance: an original observational and longitudinal
      study.
AB  - INTRODUCTION: Buprenorphine is one of the main opioid dependence treatments,
      especially in France, where it has been widely prescribed since 1996. But it can
      easily be misused and its prescription has to be followed up. In the literature,
      we found several studies on buprenorphine, but we did not find long-term
      ecological follow-up studies on buprenorphine prescription and compliance.
      MATERIAL AND METHOD: The main purpose of this study was to define stability or
      instability of the prescription of buprenorphine to opiate-addicted patients. We
      carried out a forecast study on prescription of buprenorphine over a 10-year
      period, using software collecting prescription data. We performed statistical
      analysis of the conditions and transitions of opiate-addicted patients treated
      with buprenorphine along appointments. DISCUSSION/CONCLUSION: We showed that 70%
      of buprenorphine prescriptions are stable; we assumed that our results correspond
      to buprenorphine compliance. The retention in treatment was associated with a
      positive evolution of prescription stability. Prior criminal records were the
      only factor linked to instability. We showed that collecting precise prescription
      data in face to face appointments using software, including legal prescription
      rules that guide practitioners in following buprenorphine prescription
      compliance, seemed to be a useful method to measure buprenorphine compliance.

PMID- 25052795
TI  - Connectivity of wood thrush breeding, wintering, and migration sites based on
      range-wide tracking.
AB  - Many migratory animals are experiencing rapid population declines, but migration
      data with the geographic scope and resolution to quantify the complex network of
      movements between breeding and nonbreeding regions are often lacking. Determining
      the most frequently used migration routes and nonbreeding regions for a species
      is critical for understanding population dynamics and making effective
      conservation decisions. We tracked the migration of individual Wood Thrushes
      (Hylocichla mustelina) (n = 102) from across their range with light-level
      geolocators and, for the first time, quantified migration routes and wintering
      regions for distinct breeding populations. We identified regional and species
      level migratory connectivity networks for this declining songbird by combining
      our tracking results with range-wide breeding abundance estimates and forest
      cover data. More than 50% of the species occupied the eastern wintering range
      (Honduras to Costa Rica), a region that includes only one-third of all wintering
      habitat and that is undergoing intensive deforestation. We estimated that half of
      all Wood Thrushes in North America migrate south through Florida in fall, whereas
      in spring approximately 73% funnel northward through a narrow span along the
      central U.S. Gulf Coast (88-93 degrees W). Identifying migratory networks is a
      critical step for conservation of songbirds and we demonstrated with Wood
      Thrushes how it can highlight conservation hotspots for regional populations and
      species as a whole.

PMID- 25052796
TI  - Breast MALToma.

PMID- 25052798
TI  - [Emphasizing the technological specification of glaucoma examination to promote
      mutual recognition to the results].
AB  - It is very important for us to establish the technological specifications in
      medical field. Many problems will appear if we neglect them, which include
      difficulty in approving the results of examination with each other, waste of
      medical resources and increase of patients' time and expense, lack of guarantee
      for medical quality and safety and insupportable for further study with
      collecting medical data, etc. Although many technical operations were included in
      glaucoma field, unified technical specification was still deficiency in our
      country, which will have some certain influence on the clinical and research
      work. Only increasing the understanding of importance of technological
      specifications and establishing the applications of glaucoma's technical
      specifications, our whole level of glaucoma diagnosis and treatment will be
      raised in the whole country. 

PMID- 25052797
TI  - Patient age is related to decision-making, treatment selection, and perceived
      quality of life in breast cancer survivors.
AB  - BACKGROUND: Patients with breast cancer must choose among a variety of treatment
      options when first diagnosed. Patient age, independent of extent of disease, is
      also related to quality of life. This study examined the impact of patient age on
      treatment selected, factors influencing this selection, and perceived quality of
      life. METHODS: A 62-question survey evaluating breast cancer treatment and
      quality of life was mailed to breast cancer survivors. Responses were stratified
      by age (<50, 50-65, >65 years) and extent of disease. RESULTS: Of the 1,131
      surveys mailed, 402 were included for analysis. There were 104, 179, and 119
      women aged <50, 50-65, and >65 years, respectively. The median patient age was 58
      years, and the average interval from diagnosis to survey participation was 31.5
      months. CONCLUSIONS: Young women were more likely to have undergone aggressive
      therapies and had better physical functioning than old women. Old patients
      reported good quality of life and body image. Clinicians should consider patient
      age when discussing breast cancer treatment options.

PMID- 25052799
TI  - [Thinking about the present primary open angle glaucoma early diagnosis concepts
      and methods].
AB  - Early diagnosis of primary open-angle glaucoma has not been clear and consistent
      in concepts and methods. At present, according to the pathophysiology process of
      optic nerve damage and its detection technology, early diagnosis on the concept
      still belongs to the early clinical diagnosis instead of preclinical diagnosis,
      and on the method depends on the fundus as morphological index combined with the
      visual field as functional index. The direction of early clinical diagnosis
      mainly lies in exploring more effective diagnosis index, rather than blindly
      adopt new diagnostic technology. 

PMID- 25052800
TI  - [Comments on classification of primary angle-closure glaucoma].
AB  - The new criteria to classify and diagnose primary angle-closure glaucoma (PACG)
      proposed by International Society Geographical & Epidemiological Ophthalmology
      (ISGEO) brought about not only new concept but also huge impact on Chinese
      traditional classification established in 1987. The controversy between these two
      systems has baffled Chinese ophthalmologists in years of clinical practice. The
      new criteria obviously has some concepts not suitable and not practical for
      Chinese PACG patients. However, domestic studies based on traditional
      classification are not internationally valued or accepted. Chinese own evidence
      based clinical trials are urgently needed to elucidate the pros and cons of two
      classification systems. 

PMID- 25052801
TI  - [Posture-induced intraocular pressure measurements].
AB  - OBJECTIVE: To measure the intraocular pressure (IOP) in different sleep positions
      and compare with IOP in the sitting position. METHODS: Perspective study. Thirty
      two patients with primary open angle glaucoma (POAG) and 28 normal subjects had
      IOP measured in the sitting position and then again in the supine, right lateral
      decubitus (right-lateral) and left lateral decubitus (left-lateral) positions
      with a Perkins applanation tonometer. IOPs then were measured again in the
      sitting postion after 1, 5 and 10 minutes. Two-way ANOVA was used to compare IOP
      readings in the different positions among the two study groups. Data were shown
      as mean +/- standard deviation. RESULTS: In normal subjects, the IOP values of
      the right eye were (17.5 +/- 3.8) (sitting), (19.3 +/- 3.1) (supine), (21.7 +/-
      3.7) (right-lateral) and (21.5 +/- 3.7) mmHg (left lateral) (1 mmHg = 0.133 kPa).
      The IOP values of left eye were (18.4 +/- 3.0) (sitting), (19.3 +/- 3.1)
      (supine), (20.7 +/- 2.9) (right-lateral) and (22.8 +/- 4.0) mmHg (left lateral).
      In the POAG patients, the IOP values of the right eye were (17.9 +/- 3.7)
      (sitting), (20.6 +/- 4.6) (supine), (26.1 +/- 7.1)(right-lateral) and (26.3 +/-
      5.9) mmHg (left-lateral). The IOP of the left eye in these positions were (18.2
      +/- 3.6),(20.0 +/- 4.1), (25.6 +/- 6.1) and (25.7 +/- 6.0) mmHg, respectively.
      The IOP under the right- and left-lateral positions were higher than that in
      sitting and supine in both groups. The IOP increases in all positions for POAG
      patients were significant higher than in normal subjects. The IOP decreased
      rapidly after returning from the supine to the sitting position. The IOP values
      at 1 minute, 5 minutes and 10 minutes after returning to the sitting position
      were not significantly different than the original sitting. CONCLUSIONS: The IOP
      in lateral decubitus positions is significantly higher than the IOP in sitting
      and supine positions. These differences are greater in POAG.

PMID- 25052802
TI  - [The comparison of short-term outcome between aqueous drainage pathway
      reconstruction surgery versus canaloplasty for open angle glaucoma].
AB  - OBJECTIVE: To compare the safety and efficacy between canaloplasty and aqueous
      drainage pathway reconstruction surgery in patients with open-angle glaucoma
      (OAG). METHODS: It is a retrospective case series study. Thirty-one eyes (25
      patients) with OAG were divided into canaloplasty (n = 17; 54.8%) group or
      aqueous drainage pathway reconstruction (n = 14; 45.2%) group. The intraocular
      pressure (IOP), numbers of IOP-lowering medications and incidence of
      complications were recorded at 1 day, 1 week, 1, 3, 6 and 12 months after the
      operation. Independent-samples T test was used to compare the IOP, numbers of IOP
      lowering medications before and 1, 3, 6, 12, 24 months after surgery between two
      groups. Kaplan-Meier Survival Analysis was used to analyze the success rate of
      these two surgical methods. Log rank test was used to compare the difference of
      cumulative success rate at 6, 12 months after surgery. RESULTS: The mean IOP
      values were (24.7 +/- 8.7) , (14.5 +/- 2.5), (14.9 +/- 2.5) , (14.9 +/- 2.5),
      (14.7 +/- 2.1) and (15.4 +/- 2.3) mmHg (1 mmHg = 0.133 kPa) in canaloplasty group
      at before surgery, 1, 3, 6, 12 and 24 months after surgery. The same values were
      (28.5 +/- 10.6), (14.3 +/- 3.6), (14.2 +/- 3.2), (14.3 +/- 3.6), (15.9 +/- 3.2)
      and (14.6 +/- 0.7) mmHg in aqueous drainage pathway reconstruction group. There
      was no difference in the extent of IOP reduction between these two groups
      (preoperative: t = -1.1014, P = 0.278; postoperative 1 month: t = 0.696, P =
      0.492;3 month: t = 0.594, P = 0.557; 6 month: t = 0.536, P = 0.596; 12 month: t =
      -1.127, P = 0.273; 24 month: t = 0.455, P = 0.656). There were significant
      differences (P < 0.01) in post-surgery IOP lowering medication usage between
      these two groups, while pre-surgery medication usage were similar. The incidence
      of hyphema was significantly lower in aqueous drainage pathway reconstruction
      surgery group (2 eyes) than that in canaloplasty group (11 eyes). CONCLUSIONS:
      Both canaloplasty and aqueous drainage pathway reconstruction could reduce IOP
      effectively for open-angle glaucoma. The incidence of complication was lower in
      the aqueous drainage pathway reconstruction group than canaloplasty group.
      However, long-term efficacy between these two groups is yet to be determined.

PMID- 25052803
TI  - [Meta-analysis of randomized controlled trials comparing selective laser
      trabeculoplasty with prostaglandin analogue in the primary treatment of open
      angle glaucoma or ocular hypertention].
AB  - OBJECTIVE: To compare the efficacy of selective laser trabeculoplasty (SLT)
      versus prostaglandinanalogue (PGA) in the treatment of open angle glaucoma (OAG)
      and ocular hypertension (OHT). METHODS: Literature analysis.Systematic review of
      randomized controlled trials comparing SLT versus PGA, identified by searching
      literatures including Medline (January, 1966-December, 2012), EMBASE Reviews
      (January, 1974-December, 2012) OVID Evidence-Based Medicine Reviews (January,
      1966-December, 2012), Chinese BioMedical Literature Database SinoMed (January,
      1966-December, 2012), and CNKI (January, 1999-December, 2012). RevMan 5.0 was
      used to do meta-analysis. RESULTS: Three publications reporting 3 trials, 161
      participants (231 eyes) with OHT or OAG were included for meta-analysis.IOP
      reduction favored PGA group, weighted mean difference (WMD) = -0.85[1 mmHg =
      0.133 kPa; 95% confidence interval (CI) (-1.43 to -0.27), no significant
      heterogeneity present (P = 0.82, I2 = 0%)].Success rates are equal in two groups
      [OR = 0.70, 95%CI = (0.49 to 1.19) , no significant heterogeneity present (P =
      0.58, I2 = 0%)]. Eyes underwent additional antiglaumatous interventions favored
      SLT group, OR = 1.11 [95%CI = (0.60 to 2.06), significant heterogeneity present,
      (P = 0.08, I2 = 61%)]. CONCLUSIONS: As primary therapy of OAG or OHT, SLT is no
      more effective than PGA in success rate. IOP reduction affected by SLT is not
      effective than PGA. Compared with PGA, SLT can reduce the use of anti-glaucoma
      medications.

PMID- 25052804
TI  - [Prevalence of primary glaucoma among adults aged 50 years or above population in
      Huamu community: a cross-sectional survey in Shanghai, 2011].
AB  - OBJECTIVE: To investigate the prevalence and characteristics of primary glaucoma
      in the population of Huamu community, Shanghai. METHODS: It was a population
      based cross-section study.Using random cluster sampling method, 3 neighborhood
      committees were randomly selected from Huamu community. And this survey was
      carried out by screening in community combined with diagnosis in tertiary
      hospital from March to September 2011. Residents aged more than 50 years old were
      included in this study.Information was collected on the participants' presenting
      visual acuity with habitual correction and best corrected visual acuity,
      intraocular pressure (IOP) assessed with non-contact tonometer, ocular anterior
      segment examination results with slit lamp anterior segment photography, optic
      disc examination results with fundus photography. And all glaucoma suspects
      received IOP measurement, gonioscopy, visual field test, retinal nerve fiber
      layer thickness measurement in Shanghai Eye Disease Prevention and Treatment
      center.Glaucoma was diagnosed according to International Society for Geographic
      and Epidemiological Ophthalmology. Distributions of different types of primary
      glaucoma within different groups of gender and age were described, and prevalence
      rates of primary glaucoma between different groups were compared using chi-square
      test. RESULTS: Two thousands five hundreds and twenty-eight cases were examined
      and the respond rate was 80.36%. Prevalence of primary glaucoma was 3.09%, in
      which primary open angle glaucoma (POAG) and primary angle closure glaucoma
      (PACG) were 2.85% and 0.24%. The prevalence of POAG had upward trend with age.
      The blindness rate within one or both eyes caused by POAG and PACG was 12.5% and
      3/6, and the blindness rate of POAG was lower compared with PACG. 88.89% of POAG
      in this investigation had not been previously diagnosed, and 100% of PACG had
      been previously diagnosed and received treatment. CONCLUSIONS: The prevalence of
      primary glaucoma in Huamu community is relatively high and the previous
      diagnostic and treatment rate of POAG are relatively low. Early screening and
      health education for primary glaucoma are important in blindness prevention work
      in the future.

PMID- 25052805
TI  - [Analysis of ocular changes in children craniopharyngioma].
AB  - OBJECTIVE: To analyze the characteristics of ocular changes in children
      craniopharyngioma. METHODS: Retrospective case series study. The clinical data of
      34 eyes from 17 patients with children craniopharyngioma treated at the
      affiliated Beijing Tiantan Hospital, Capital Medical University from September
      2011 to May 2012 were collected. Records of preoperative clinical examinations
      including best corrected visual acuity (BCVA), visual field test, optic disc
      findings, size and location of the tumor were analyzed. RESULTS: The age of the
      patients was from 5 to 14 years old [mean (10.29 +/- 3.22) years] with the
      male/female ratio of 1.83: 1. The most affected age group was 8 to 12 years old.
      Deficits in BCVA occurred in 79.41% (27/34). Abnormal optic disc findings
      occurred in 44.12% which included optic disk edema 5.9% (2/34), atrophic changes
      of the optic nerve 32.35% (11/34) and pale optic disc 5.9% (2/34). Various visual
      field defects were 76.47% (26/34). CONCLUSION: Declines of visual acuities and
      defects of visual fields were more severe than optic disc damages in children
      patients with craniopharyngioma.

PMID- 25052807
TI  - [Progression of flicker perimetry in clinical application].
AB  - Flicker perimetry measures the function of retina by stimulating it using
      flickering light. It has three test modes:contrast modulation flicker, critical
      flicker fusion frequency and luminance pedestal flicker. These 3 modes have their
      own characteristics. Flicker perimetry shows a higher sensitivity than white
      white standard automated perimetry in early diagnosis of glaucoma. It also has
      advantages in the diagnosis for age-related macular degeneration, diabetic
      retinopathy and other retinal diseases. With further understanding of the flicker
      perimetry, its clinical application will gradually expand. In this paper, the
      basic principle and clinical application are reviewed. 

PMID- 25052806
TI  - [Clinical observation on removal of small foreign bodies touching the optic nerve
      in the deep orbital region].
AB  - OBJECTIVE: To evaluate the treatment and therapeutic efficacy of extraction of
      deep intra-orbital little foreign bodies touching the optic nerve. METHODS: In
      this retrospective study, the clinical data of 5 deep intra-orbital little
      foreign bodies cases were recorded from 2008 to 2012 in Eye Center, PLA 474th
      Hospital. The treatment and therapeutic effect were analyzed. RESULT: The
      properties of the foreigen bodies in these 5 cases weremetallic in 4 cases and
      nonmetallic in 1 cases. The preoperative visual acurity were no light perception
      in 3 cases, light perception in 1 case, and hand movement in 1 case. The
      complications included vitreous hemorrhage which had been temponaded with silicon
      oil in other hospital (1 case), traumatic cataract, retinal and choroid
      detachment (1 case), traumatic retinal detachment and vitreous hemorrhage (2
      cases). In all the cases, computed tomography (CT) indicated deep orbital foreign
      bodies touching the optic nerve, and clinical manifestations showed optic nerve
      injuries. The Foreign bodies were extracted successfully in all the cases. The
      postoperative visual acuity improved in 3 cases, however 2 cases remained blind.
      CONCLUSIONS: Carefully positioned with CT preoperatively, Deep intra-orbital
      little foreign bodies touching the optic nerve could be exctracted by lateral
      orbitotomy and the vision could improve in some patients.

PMID- 25052808
TI  - [Distal axonopathy in glaucomatous optic neuropathy].
AB  - Glaucoma is a complex class of degenerative optic neuropathy. Multiple mechanisms
      were involved in glaucomatous optic nerve damage. In recent years, research
      progression has been made in the relationship between axonal degeneration and
      glaucoma with more attention and effort dedicated to explicate the pathogenesis
      of progressive optic nerve injury. Series of studies indicate that the interplay
      between distal axonal degeneration and axon neuron damage may play an important
      role in the progression of the disease. Distal axonal lesions may contribute to
      glaucoma, the pathological basis may be the retrograde degeneration of the optic
      nerve in visual pathways. In this article, we review the latest findings in the
      distal axonal degeneration and glaucomatous optic neuropathy. 

PMID- 25052809
TI  - [Advance studies of Slit-Robo signal pathway and its roles in ocular
      neovascularisation].
AB  - The migration and patterning of axons and blood vessels share similar guidance
      mechanisms. Slits and their Roundabout (Robo) receptors were initially
      characterized as repulsive guidance cues for neuronal axons and mediate the
      migration of neuronal precursor cells during neural development. In recent years,
      the research of Slit/Robo signal pathway on neovascularization has become one of
      hot topics. This review will focus on the role of Slit/Robo signal pathway in
      ocular neovascularization to promote the research of Slit/Robo signaling on
      ophthalmology. 

PMID- 25052810
TI  - Temperature-activity relationships in Meligethes aeneus: implications for pest
      management.
AB  - BACKGROUND: Pollen beetle (Meligethes aeneus F.) management in oilseed rape
      (Brassica napus L.) has become an urgent issue in the light of insecticide
      resistance. Risk prediction advice has relied upon flight temperature thresholds,
      while risk assessment uses simple economic thresholds. However, there is
      variation in the reported temperature of migration, and economic thresholds vary
      widely across Europe, probably owing to climatic factors interacting with beetle
      activity and plant compensation for damage. The effect of temperature on flight,
      feeding and oviposition activity of M. aeneus was examined in controlled
      conditions. RESULTS: Escape from a release vial was taken as evidence of flight
      and was supported by video observations. The propensity to fly followed a sigmoid
      temperature-response curve between 6 and 23  degrees C; the 10, 25 and 50% flight
      temperature thresholds were 12.0-12.5  degrees C, 13.6-14.2  degrees C and 15.5
      16.2  degrees C, respectively. Thresholds were slightly higher in the second of
      two flight bioassays, suggesting an effect of beetle age. Strong positive
      relationships were found between temperature (6-20  degrees C) and the rates of
      feeding and oviposition on flower buds of oilseed rape. CONCLUSION: These
      temperature relationships could be used to improve M. aeneus migration risk
      assessment, refine weather-based decision support systems and modulate damage
      thresholds according to rates of bud damage.

PMID- 25052811
TI  - Bis-heteroleptic ruthenium(II) complex of a triazole ligand as a selective probe
      for phosphates.
AB  - A new bis-heteroleptic ruthenium(II) complex (1) of 2-(1-methyl-1H-1,2,3-triazol
      4-yl) pyridine (L) ligand was extensively explored for anion sensing studies.
      1[PF6]2 shows selective sensing of dihydrogen phosphate (H2PO4(-))/hydrogen
      pyrophosphate (HP2O7(3-)) among halides, HCO3(-), AcO(-), NO3(-), ClO4(-), HSO4(
      ), OH(-), BzO(-), H2PO4(-), and HP2O7(3-) in acetonitrile. Enhancement of
      emission intensity of 1[PF6]2 along with a 10 nm red shift of the emission
      maximum is observed in the presence of H2PO4(-)/HP2O7(3-) selectively. The
      photoluminescence (PL) titration experiment of 1[PF6]2 results in binding
      constants (K(a)) of 5.28 * 10(4) M(-1) and 4.67 * 10(4) M(-1) for H2PO4(-) and
      HP2O7(3-), respectively, which is in good agreement with the Ka values obtained
      from UV-vis titration experiments (2.97 * 10(4) M(-1) and 2.45 * 10(4) M(-1) for
      H2PO4(-) and HP2O7(3-), respectively). High selectivity of 1[PF6]2 toward these
      two anions in acetonitrile is further confirmed by PL intensity measurement of
      1[PF6]2 upon addition of these two anions in the presence of a large excess of
      other competitive anions. Further, considerable changes in the lifetime (tau) as
      well as in the decay pattern of 1[PF6]2 in the presence of H2PO4(-)/HP2O7(3-)
      among all tested anions support the selective binding property of 1[PF6]2 toward
      these two anions. Significant downfield shift of the triazole -CH proton of
      1[PF6]2 with 1 equiv of H2PO4(-) (Deltadelta = 0.26 ppm) and HP2O7(3-)
      (Deltadelta = 0.23 ppm) in deuterated dimethyl sulfoxide proclaim binding
      mechanism via C-H...anion interaction in solution state. Finally, single-crystal
      X-ray structural analysis confirms the first example of dihydrogen pyrophosphate
      (H2P2O7(2-)) recognition via solitary C-H...anion interactions.

PMID- 25052813
TI  - Children's explanations as a window into their intuitive theories of the social
      world.
AB  - Social categorization is an early emerging and robust component of social
      cognition, yet the role that social categories play in children's understanding
      of the social world has remained unclear. The present studies examined children's
      (N = 52 four- and five-year olds) explanations of social behavior to provide a
      window into their intuitive theories of how social categories constrain human
      action. Children systematically referenced category memberships and social
      relationships as causal-explanatory factors for specific types of social
      interactions: harm among members of different categories more than harm among
      members of the same category. In contrast, they systematically referred to
      agents' mental states to explain the reverse patterns of behaviors: harm among
      members of the same category more than harm among members of different
      categories. These data suggest that children view social category memberships as
      playing a causal-explanatory role in constraining social interactions.

PMID- 25052812
TI  - Code blue: Acinetobacter baumannii, a nosocomial pathogen with a role in the oral
      cavity.
AB  - Actinetobacter baumannii is an important nosocomial pathogen that can cause a
      wide range of serious conditions including pneumonia, meningitis, necrotizing
      fasciitis and sepsis. It is also a major cause of wound infections in military
      personnel injured during the conflicts in Afghanistan and Iraq, leading to its
      popular nickname of 'Iraqibacter'. Contributing to its success in clinical
      settings is resistance to environmental stresses such as desiccation and
      disinfectants. Moreover, in recent years there has been a dramatic increase in
      the number of A. baumannii strains with resistance to multiple antibiotic
      classes. Acinetobacter baumannii is an inhabitant of oral biofilms, which can act
      as a reservoir for pneumonia and chronic obstructive pulmonary disease.
      Subgingival colonization by A. baumannii increases the risk of refractory
      periodontitis. Pathogenesis of the organism involves adherence, biofilm formation
      and iron acquisition. In addition, A. baumannii can induce apoptotic cell death
      in epithelial cells and kill hyphal forms of Candida albicans. Virulence factors
      that have been identified include pili, the outer membrane protein OmpA,
      phospholipases and extracellular polysaccharide. Acinetobacter baumannii can
      sense blue light through a blue-light sensing using flavin (BLUF) domain protein,
      BlsA. The resulting conformational change in BlsA leads to changes in gene
      expression, including virulence genes. 

PMID- 25052814
TI  - [Minimally invasive oncological surgery of the upper gastrointestinal tract :
      state of the art].

PMID- 25052815
TI  - [Spectrum of laparoscopic surgery for gastric tumors].
AB  - Minimally invasive operative procedures are increasingly being used for treating
      tumors of the upper gastrointestinal tract. While minimally invasive surgery
      (MIS) has become established as a standard procedure for benign tumors and
      gastrointestinal stromal tumors (GIST) based on current studies, the significance
      of MIS in the field of gastric cancer is the topic of heated debate. Until now
      the majority of studies and meta-analyses on gastric cancer have come from Asia
      and these indicate the advantages of MIS in terms of intraoperative blood loss,
      minor surgical complications and swifter convalescence although without any
      benefits in terms of long-term oncological results and quality of life. Unlike in
      Germany, gastric cancer in Asia with its unchanged high incidence rate, 50 %
      frequency of early carcinoma and predominantly distal tumor localization is
      treated at high-volume centres. Due to the proven marginal advantages of MIS over
      open resection described in the published studies no general recommendation for
      laparoscopic surgery of gastric cancer can currently be given. 

PMID- 25052816
TI  - [Minimally invasive surgery of primary and secondary liver tumors : indications,
      techniques and results].
AB  - BACKGROUND: Initially, mainly superficial liver lesions were resected
      laparoscopically but now even major resections are performed using a minimally
      invasive procedure. Careful selection of suitable patients is of key importance.
      AIMS AND METHODS: This article describes the current state of the art in patient
      selection and choice of the appropriate laparoscopic technique based on a review
      of the recent literature. Perioperative and oncological outcome parameters of
      laparoscopic liver resection are presented. RESULTS: Laparoscopic liver resection
      offers significant benefits compared to open liver resection in terms of reduced
      intraoperative blood loss, reduced overall and liver-specific complications and
      length of hospital stay without compromising oncological outcomes. CONCLUSION:
      Lesions in the peripheral anterolateral segments (segments 2, 3, 4b, 5 and 6) are
      particularly suitable for laparoscopic liver resection. Access to the
      posterosuperior segments 1, 4a, 7 and 8 is more challenging but safe and feasible
      in experienced centers.

PMID- 25052817
TI  - Development of schooling behaviour during the downstream migration of Atlantic
      salmon Salmo salar smolts in a chalk stream.
AB  - The downstream migratory behaviour of wild Atlantic salmon Salmo salar smolts was
      monitored using passive integrated transponder (PIT) antennae systems over 10
      years in the lower reaches of a small chalk stream in southern England, U.K. The
      timing of smolt movements and the likely occurrence of schooling were
      investigated and compared to previous studies. In nine of the 10 consecutive
      years of study, the observed diel downstream patterns of S. salar smolt migration
      appeared to be synchronized with the onset of darkness. The distribution of time
      intervals between successive nocturnal detections of PIT-tagged smolts was as
      expected if generated randomly from observed hourly rates. There were, however,
      significantly more short intervals than expected for smolts detected migrating
      during the day. For each year from 2006 to 2011, the observed 10th percentile of
      the daytime intervals was <4 s, compared to >=55 s for the simulated random
      times, indicating greater incidence of groups of smolts. Groups with the shortest
      time intervals between successive PIT tag detections originated from numerous
      parr tagging sites (used as a proxy for relatedness). The results suggest that
      the ecological drivers influencing daily smolt movements in the lower reaches of
      chalk stream catchments are similar to those previously reported at the onset of
      migration for smolts leaving their natal tributaries; that smolts detected
      migrating during the night are moving independently following initiation by a
      common environmental factor (presumably darkness), whereas those detected
      migrating during the day often move in groups, and that such schools may not be
      site (kin)-structured. The importance of understanding smolt migratory behaviour
      is considered with reference to stock monitoring programmes and enhancing
      downstream passage past barriers.

PMID- 25052818
TI  - Concurrent appendiceal and umbilical endometriosis: a case report and review of
      the literature.
AB  - INTRODUCTION: Endometriosis affects 3 to 10 percent of women of reproductive age.
      Most of the time it involves the pelvis; however, sites of endometriosis have
      been reported almost anywhere in the body. Appendiceal and primary umbilical
      endometriosis are considered rare loci, making accurate diagnosis elusive. Here
      we present the case of a 46-year-old woman with concurrent appendiceal and
      umbilical endometriosis. CASE PRESENTATION: A 46-year-old Greek woman presented
      with a large mass in the lower abdomen adhering to the surrounding organs. She
      reported recurrent lower abdominal and pelvic pain and the presence of a dark
      blue hard nodule at the umbilicus. She had no previous medical, surgical or
      gynecological history. Her physical examination and laboratory test results were
      without any significant findings. The laparotomy revealed a fibromatose uterus
      adhering to the rectum and a urinary cyst and a palpable mass in the vermiform
      appendix. A hysterectomy and an appendectomy were performed. The umbilical mass
      was also excised. Pathology revealed endometriosis of the umbilicus and the
      appendix. The postoperative period was uneventful and she was discharged.
      CONCLUSIONS: Endometriosis, although rare, should always be considered in women
      of reproductive age, presenting with cyclic pain. The diagnosis is, most of the
      time, difficult and requires a high degree of clinical suspicion. The clinical
      doctor should be aware that endometriosis can sometimes be multifocal, thus a
      thorough investigation is required in all cases.

PMID- 25052819
TI  - Children who are deaf or hard of hearing in inclusive educational settings: a
      literature review on interactions with peers.
AB  - This review is conducted to describe how children who are deaf or hard of hearing
      (D/HH) interact with hearing peers in inclusive settings, illustrate the
      difficulties and challenges faced by them in interacting with peers, and identify
      effective interventions that promote their social interaction in inclusive
      education. A systematic search of databases and journals identified 21 papers
      that met the inclusion criteria. Two broad themes emerged from an analysis of the
      literatures, which included processes and outcomes of interactions with peers and
      intervention programs. The research indicates that children who are D/HH face
      great difficulties in communicating, initiating/entering, and maintaining
      interactions with hearing peers in inclusive settings. The co-enrollment and
      social skills training programs are considered to be effective interventions for
      their social interaction. Communication abilities and social skills of children
      who are D/HH, responses of children with normal hearing, and the effect of
      environment are highlighted as crucial aspects of social interactions. In
      addition, future research is needed to study the interaction between children who
      are D/HH and hearing peers in natural settings, at different stages of school
      life, as well as improving social interaction and establishing an inclusive
      classroom climate for children who are D/HH. 

PMID- 25052820
TI  - Brachial pulse pressure and cardiovascular or all-cause mortality in the general
      population: a meta-analysis of prospective observational studies.
AB  - This study aimed to quantitatively evaluate the predictive value of brachial
      pulse pressure and cardiovascular or all-cause mortality in the general
      population based on prospective observational studies by conducting a meta
      analysis. Only prospective observational studies investigating baseline brachial
      pulse pressure and cardiovascular or all-cause mortality risk were selected from
      PubMed and Embase databases until July 2013. Fourteen studies involving 510,456
      participants were analyzed. Pooled risk ratio (RR) of cardiovascular and all
      cause mortality for the highest vs lowest brachial pulse pressure category was
      1.80 (95% confidence interval [CI], 1.49-2.17) and 1.32 (95% CI, 1.23-1.41),
      respectively. Pooled RR of cardiovascular and all-cause mortality per 10 mm Hg
      pulse pressure increment was 1.13 (95% CI, 1.10-1.17) and 1.09 (95% CI, 1.07
      1.11), respectively. Wide brachial pulse pressure is associated with greater risk
      of cardiovascular and all-cause mortality. However, more well-designed studies
      specifically on age and sex are needed to further confirm these findings.

PMID- 25052821
TI  - Controlled reoxygenation during cardiopulmonary bypass decreases markers of organ
      damage, inflammation, and oxidative stress in single-ventricle patients
      undergoing pediatric heart surgery.
AB  - OBJECTIVE: Single-ventricle patients undergoing pediatric heart surgery are a
      high-risk group owing to reoxygenation injury during cardiopulmonary bypass
      (CPB). The present study investigated the effects of controlled reoxygenation CPB
      on biomarkers of organ damage, inflammation, stress, and long-term functional
      outcomes in cyanotic patients with either a single or double ventricle during
      open heart surgery. METHODS: Cyanotic patients with either a single (n = 32) or
      double (n = 47) ventricle undergoing surgical correction were randomized to
      receive CPB using either standard oxygen levels or controlled reoxygenation. The
      markers of cardiac injury, inflammation, stress, and cerebral and hepatic injury
      were measured preoperatively, at 10 and 30 minutes after starting CPB, and at 10
      minutes and 4 and 24 hours after CPB. The data were analyzed using a mixed
      regression model. RESULTS: No difference was found in the pre- or intraoperative
      characteristics between the standard and controlled reoxygenation CPB groups for
      single- or double-ventricle patients. In the single-ventricle patients,
      controlled reoxygenation CPB significantly (P < .05) decreased the markers of
      organ damage, inflammation, stress, and oxidative stress. In contrast, the
      markers of inflammation and cardiac injury were not altered by controlled
      reoxygenation CPB in the double-ventricle patients. CONCLUSIONS: Controlled
      reoxygenation CPB decreased the markers of organ damage, stress, inflammation,
      and oxidative stress in single-ventricle patients undergoing cardiac surgery.

PMID- 25052822
TI  - Straight deep hypothermic circulatory arrest for cerebral protection during
      aortic arch surgery: Safe and effective.
AB  - OBJECTIVE: To evaluate our extensive clinical experience using deep hypothermic
      circulatory arrest (DHCA) as a sole method of cerebral protection during aortic
      arch surgery, with an emphasis on determining the safe duration of DHCA. METHODS:
      A total of 490 consecutive patients (303 males [61.8%], mean age, 62.7 +/- 13.5
      years) underwent surgical interventions on the aortic arch with straight DHCA for
      cerebral protection. Of the procedures, 65 (13.3%) were either urgent or
      emergency. Aortic aneurysms (n = 417, 85.1%) and dissections (n = 71, 14.5%) were
      the main indications for surgery. RESULTS: The mean DHCA duration was 29.2 +/-
      7.9 minutes at a mean bladder temperature of 18.7 degrees C. The overall
      mortality was 2.4% (12 of 490), and elective mortality was 1.4% (6 of 425). The
      seizure rate was 1.4% (7 of 490). Six patients (1.2%) developed renal failure
      that required dialysis. The postoperative stroke rate was 1.6% (8 of 490) and was
      1.2% (5 of 425) for the elective cases. The overall stroke rate for patients
      requiring <50 minutes of DHCA was 1.3% (6 of 478), significantly different from
      the 16.7% (2 of 12) stroke rate for patients requiring >50 minutes of DHCA (P =
      .014). Multivariate analysis revealed a DHCA time >50 minutes (odds ratio, 5.11
      +/- 4.01, P = .038) and aortic dissection (odds ratio, 3.59 +/- 1.72, P = .008)
      to be strong predictors of composite adverse outcomes. CONCLUSIONS: Straight DHCA
      is a safe and effective technique of cerebral protection for the absolute
      majority of interventions involving the aortic arch. At experienced centers, up
      to 50 minutes of DHCA can be considered safe, without significant postoperative
      mortality or neurologic sequelae.

PMID- 25052823
TI  - Is it possible to assess the best mitral valve repair in the individual patient?
      Preliminary results of a finite element study from magnetic resonance imaging
      data.
AB  - OBJECTIVES: Finite element modeling was adopted to quantitatively compare, for
      the first time and on a patient-specific basis, the biomechanical effects of a
      broad spectrum of different neochordal implantation techniques for the repair of
      isolated posterior mitral leaflet prolapse. METHODS: Cardiac magnetic resonance
      images were acquired from 4 patients undergoing surgery. A patient-specific 3
      dimensional model of the mitral apparatus and the motion of the annulus and
      papillary muscles were reconstructed. The location and extent of the prolapsing
      region were confirmed by intraoperative findings, and the mechanical properties
      of the mitral leaflets, chordae tendineae and expanded polytetrafluoroethylene
      neochordae were included. Mitral systolic biomechanics was simulated under
      preoperative conditions and after 5 different neochordal procedures: single
      neochorda, double neochorda, standard neochordal loop with 3 neochordae of the
      same length and 2 premeasured loops with 1 common neochordal loop and 3 different
      branched neochordae arising from it, alternatively one third and two thirds of
      the entire length. RESULTS: The best repair in terms of biomechanics was achieved
      with a specific neochordal technique in the single patient, according to the
      location of the prolapsing region. However, all techniques achieved a slight
      reduction in papillary muscle forces and tension relief in intact native chordae
      proximal to the prolapsing region. Multiple neochordae implantation improved the
      repositioning of the prolapsing region below the annular plane and better
      redistributed mechanical stresses on the leaflet. CONCLUSIONS: Although applied
      on a small cohort of patients, systematic biomechanical differences were noticed
      between neochordal techniques, potentially affecting their short- to long-term
      clinical outcomes. This study opens the way to patient-specific optimization of
      neochordal techniques.

PMID- 25052829
TI  - The spontaneous formation of stereotypes via cumulative cultural evolution.
AB  - All people share knowledge of cultural stereotypes of social groups--but what are
      the origins of these stereotypes? We examined whether stereotypes form
      spontaneously as information is repeatedly passed from person to person. As
      information about novel social targets was passed down a chain of individuals,
      what initially began as a set of random associations evolved into a system that
      was simplified and categorically structured. Over time, novel stereotypes emerged
      that not only were increasingly learnable but also allowed generalizations to be
      made about previously unseen social targets. By illuminating how cognitive and
      social factors influence how stereotypes form and change, these findings show how
      stereotypes might naturally evolve or be manipulated.

PMID- 25052825
TI  - Regulatory T cells enhance mesenchymal stem cell survival and proliferation
      following autologous cotransplantation in ischemic myocardium.
AB  - OBJECTIVES: We sought to investigate if autologous freshly isolated regulatory T
      cells (Tregs) provide a protective and supportive role when cotransplanted with
      mesenchymal stem cells (MSCs). METHODS: In a porcine model of chronic ischemia,
      autologous MSCs were isolated and expanded ex vivo for 4 weeks. Autologous Treg
      cells were freshly isolated from 100 mL peripheral blood and purified by
      fluorescence-activated cell sorting. MSCs and Treg cells were then cotransplanted
      into the chronic ischemic myocardium of Yorkshire pigs by direct intramyocardial
      injection (1.2 * 10(8) MSCs plus an average of 1.5 million Treg cells in 25
      injection sites). Animals were killed 6 weeks postinjection to study the fate of
      the cells and compare the effect of combined MSCs + Treg cells transplantation
      versus MSCs alone. RESULTS: The coinjection of MSCs along with Tregs was safe and
      no deleterious side effects were observed. Six weeks after injection of the cell
      combination, spherical MSCs clusters with thin layer capsules were found in the
      injected areas. In animals treated with MSCs only, the MSC clusters were less
      organized and not encapsulated. Immunofluorescent staining showed CD25+ cells
      among the CD90+ (MSC marker) cells, suggesting that the injected Treg cells
      remained present locally, and survived. Factor VIII+ cells were also prevalent
      suggesting new angiogenesis. We found no evidence that coinjections were
      associated with the generation of cardiac myocytes. CONCLUSIONS: The
      cotransplantation of Treg cells with MSCs dramatically increased the MSC survival
      rate, proliferation, and augmented their role in angiogenesis, which suggests a
      new way for future clinical application of cell-based therapy.

PMID- 25052830
TI  - When you think about it, your past is in front of you: how culture shapes spatial
      conceptions of time.
AB  - In Arabic, as in many languages, the future is "ahead" and the past is "behind."
      Yet in the research reported here, we showed that Arabic speakers tend to
      conceptualize the future as behind and the past as ahead of them, despite using
      spoken metaphors that suggest the opposite. We propose a new account of how space
      time mappings become activated in individuals' minds and entrenched in their
      cultures, the temporal-focus hypothesis: People should conceptualize either the
      future or the past as in front of them to the extent that their culture (or
      subculture) is future oriented or past oriented. Results support the temporal
      focus hypothesis, demonstrating that the space-time mappings in people's minds
      are conditioned by their cultural attitudes toward time, that they depend on
      attentional focus, and that they can vary independently of the space-time
      mappings enshrined in language. 

PMID- 25052831
TI  - The development of the experience and anticipation of regret.
AB  - Although recent studies have established that children experience regret from
      around 6 years, we do not yet know when the ability to anticipate this emotion
      emerges, despite the importance of the anticipation of regret in decision-making.
      We examined whether children will anticipate they will feel regret if they were
      to find out in a box-choosing game that, had they made a different choice, they
      would have obtained a better prize. Experiment 1 replicated Guttentag and
      Ferrell's study in which children were asked what they hoped was in a non-chosen
      box. Even 8- to 9-year olds find this question difficult. However, when asked
      what might make them feel sadder, 7- to 8-year olds (but not younger children)
      predicted that finding the larger prize in the unchosen box would make them feel
      this way. In Experiments 2 and 3, children predicted how they would feel if the
      unchosen box contained either a larger or smaller prize, in order to examine
      anticipation of both regret and of relief. Although 6- to 7-year olds do
      experience regret when they find out they could have won a better prize, they do
      not correctly anticipate feeling this way. By around 8 years, the majority of
      children are able to anticipate both regret and relief. 

PMID- 25052832
TI  - Platelet function in Takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TK) includes a transient left ventricular dysfunction
      without obstructive coronary disease, sometimes after stressful situations with
      elevated cathecolamines. Since catecholamines activate platelets we aimed to
      study the platelet influence in a TK setting. We included 32 patients with a TK
      diagnosis, 13 with an acute coronary syndrome (ACS) and 18 healthy volunteers.
      Once consent informed was obtained, blood samples were extracted and processed
      (at admission and after 3 months follow-up). Clinical, ecg, echocardiographic and
      angiographic features were thoroughly recorded.Previous treatment before
      admission was similar between groups. No differences were observed in clinical
      features or any of the acute markers studied regarding platelet reactivity
      between TK compared to ACS. After follow-up, aggregation levels and platelet
      reactivity showed differences, mainly due to the antithrombotic therapy
      prescribed at discharge, but similar to volunteers. Circulating epinephrine
      during the acute phase was significantly higher in TK (p < 0.001). Patients with
      higher levels of epinephrine had elevated platelet activation and aggregation
      after 3 months. No differences were observed in Takotsubo acute platelet
      aggregation compared to patients with ACS, in spite of higher blood levels of
      adrenaline. Takotsubo patients had elevated platelet aggregation and activation
      compared with ACS patients at 3 months follow-up because they were less
      frequently on chronic clopidogrel and ASA. However, they had similar platelet
      aggregation and activation levels to healthy volunteers despite treatment with
      low-dose ASA. Takotsubo patients who had higher levels of adrenaline in the acute
      phase displayed increased platelet reactivity during follow-up.

PMID- 25052833
TI  - Efficacy and safety of thrombolysis for stroke of unknown onset time: a meta
      analysis.
AB  - Current stroke treatment guidelines exclude unknown onset stroke (UOS) patients
      from thrombolytic therapy even though several studies have reported significant
      treatment efficacy and safety. We performed a meta-analysis of relevant studies
      retrieved by systematic searches of the PubMed, Embase, and Cochrane databases up
      to December 31, 2013. Dichotomized modified Rankin Scale (mRS) scores 0-1 at 90
      days, mRS 0-2 at 90 days, overall mortality, and symptomatic intracranial
      hemorrhage (sICH) incidence were collected as primary outcome measures. Fixed
      effects meta-analytical models were used, and between-study heterogeneity was
      assessed. Eleven studies encompassing 1,832 patients were included. In case
      control studies of UOS patients, thrombolysis was associated with a significant
      increase in the proportion of patients with mRS scores of 0-1 (OR 2.37; 95% CI
      1.20-4.69; P = 0.013) and 0-2 (OR 2.03; 95% CI 1.26-3.30; P = 0.004) without
      increased mortality or sICH incidence. In studies comparing thrombolysis-treated
      UOS to thrombolysis-treated known onset stroke, however, fewer UOS patients had
      mRS scores of 0-1 (OR 0.70; 95% CI 0.51-0.97; P = 0.033) with no change in
      mortality, sICH incidence, or patients with mRS of 0-2. Subgroup analysis based
      on imaging criteria and time window of thrombolysis indicated that UOS patients
      treated within 3 h after first found abnormal and those with early ischemic
      changes restricted to <1/3 of the middle cerebral artery territory gained more
      benefit from thrombolysis treatment than the whole UOS population. Randomized
      controlled trials are warranted to confirm the efficacy of thrombolysis in this
      UOS subgroup.

PMID- 25052834
TI  - Racial differences in resistance to P2Y12 receptor antagonists in type 2 diabetic
      subjects.
AB  - Although resistance to the P2Y12 antagonist clopidogrel is linked to altered drug
      metabolism, some studies suggest that these pharmacokinetic abnormalities only
      partially account for drug resistance. To circumvent pharmacokinetic
      complications and target P2Y12 receptor function we applied the direct P2Y12
      antagonist 2-methylthio-AMP (2-methylthioadenosine 5'-monophosphate
      triethylammonium salt) to purified platelets ex vivo. Platelets were purified
      from healthy and type 2 diabetes mellitus (T2DM) patients and stimulated with
      thrombin or the selective protease-activated receptor agonists, protease
      activated receptor 1-activating peptide (PAR1-AP), or PAR4-AP. Platelet
      activation as measured by alphaIIbbeta3 activation, and P-selectin expression was
      monitored in 141 subjects. Our results demonstrate that, compared with healthy
      subjects, platelets from diabetic patients are resistant to inhibition by 2
      methylthio-AMP, demonstrating P2Y12 pharmacodynamic defects among diabetic
      patients. Inhibition of thrombin-mediated alphaIIbbeta3 activation by 2
      methylthio-AMP was lower in diabetic platelets versus healthy platelets. Subgroup
      analysis revealed a racial difference in the resistance to 2-methylthio-AMP. We
      found no resistance in platelets from diabetic African Americans; they were
      inhibited by 2-methylthio-AMP equally as well as platelets from healthy African
      Americans. In contrast, platelets from Caucasian patients with diabetes were
      resistant to P2Y12 antagonism compared with healthy Caucasians. Multivariable
      analysis demonstrated that other variables, such as obesity, age, or gender,
      could not account for the differential resistance to 2-methylthio-AMP among
      races. These results suggest that in addition to altered drug metabolism, P2Y12
      receptor function itself is altered in the Caucasian diabetic population. The
      racial difference in platelet function in T2DM is a novel finding, which may lead
      to differences in treatment as well as new targets for antiplatelet therapy. 

PMID- 25052835
TI  - Dopamine D1 receptor signaling: does GalphaQ-phospholipase C actually play a
      role?
AB  - Despite numerous studies showing therapeutic potential, no central dopamine D1
      receptor ligand has ever been approved, because of potential limitations, such as
      hypotension, seizures, and tolerance. Functional selectivity has been widely
      recognized as providing a potential mechanism to develop novel therapeutics from
      existing targets, and a highly biased, functionally selective D1 ligand might
      overcome some of the past limitations. SKF-83959 [6-chloro-3-methyl-1-(m-tolyl)
      2,3,4,5-tetrahydro-1H-benzo[d]azepine-7,8-diol] is reported to be a highly biased
      D1 ligand, having full agonism at D1-mediated activation of phospholipase C (PLC)
      signaling (via GalphaQ) and antagonism at D1-mediated adenylate cyclase signaling
      (via GalphaOLF/S). For this reason, numerous studies have used this compound to
      elucidate the physiologic role of D1-PLC signaling, including a novel molecular
      mechanism (GalphaQ-PLC activation via D1-D2 heterodimers). There is, however,
      contradictory literature that suggests that SKF-83959 is actually a partial
      agonist at both D1-mediated adenylate cyclase and beta-arrestin recruitment.
      Moreover, the D1-mediated PLC stimulation has also been questioned. This
      Minireview examines 30 years of relevant literature and proposes that the data
      strongly favor alternate hypotheses: first, that SKF-83959 is a typical D1
      partial agonist; and second, that the reported activation of PLC by SKF-83959 and
      related benzazepines likely is due to off-target effects, not actions at D1
      receptors. If these hypotheses are supported by future studies, it would suggest
      that caution should be used regarding the role of PLC and downstream pathways in
      D1 signaling. 

PMID- 25052837
TI  - Bone mechanobiology, gravity and tissue engineering: effects and insights.
AB  - Bone homeostasis strongly depends on fine tuned mechanosensitive regulation
      signals from environmental forces into biochemical responses. Similar to the
      ageing process, during spaceflights an altered mechanotransduction occurs as a
      result of the effects of bone unloading, eventually leading to loss of functional
      tissue. Although spaceflights represent the best environment to investigate near
      zero gravity effects, there are major limitations for setting up experimental
      analysis. A more feasible approach to analyse the effects of reduced
      mechanostimulation on the bone is represented by the 'simulated microgravity'
      experiments based on: (1) in vitro studies, involving cell cultures studies and
      the use of bioreactors with tissue engineering approaches; (2) in vivo studies,
      based on animal models; and (3) direct analysis on human beings, as in the case
      of the bed rest tests. At present, advanced tissue engineering methods allow
      investigators to recreate bone microenvironment in vitro for mechanobiology
      studies. This group and others have generated tissue 'organoids' to mimic in
      vitro the in vivo bone environment and to study the alteration cells can go
      through when subjected to unloading. Understanding the molecular mechanisms
      underlying the bone tissue response to mechanostimuli will help developing new
      strategies to prevent loss of tissue caused by altered mechanotransduction, as
      well as identifying new approaches for the treatment of diseases via drug
      testing. This review focuses on the effects of reduced gravity on bone
      mechanobiology by providing the up-to-date and state of the art on the available
      data by drawing a parallel with the suitable tissue engineering systems.

PMID- 25052836
TI  - TrkB interacts with ErbB4 and regulates NRG1-induced NR2B phosphorylation in
      cortical neurons before synaptogenesis.
AB  - BACKGROUND: Neuregulin 1 (NRG1) and NMDARs play important roles in various
      neuronal functions including neural development. NMDARs also promote many
      cellular events such as proliferation and survival of neuroblasts before synapse
      formation. Although many recent studies have indicated that NRG1 regulates NMDAR
      function in cortical neurons, the effect of NRG1 on NMDAR activation before
      synapse formation is not well studied. RESULTS: NRG1 induces activation of NMDAR
      subunit NR2B, and tropomyosin-related kinase receptor B (TrkB), the receptor for
      BDNF via activation of phospholipase C-gamma (PLC-gamma) in immature primary
      cortical neurons. Our data using TrkB inhibitor (K252a), TrkB siRNA and TrkB-/-
      neurons demonstrated that TrkB inhibition suppresses NRG1-induced NR2B activation
      in neurons. We found that NRG1 stimulation leads to GABAA receptor-mediated TrkB
      activation. Co-immunoprecipitation and proximity ligase assay showed that TrkB
      interacts with ErbB4 (NRG1 receptor) and the TrkB-ErbB4 interaction was increased
      following NRG1 treatment. A significant reduction in TrkB-ErbB4 interaction was
      observed in the prefrontal cortex of schizophrenia subjects. We found significant
      increase in released BDNF levels following NRG1 treatment, which was inhibited by
      ErbB4 inhibitor, AG1478. In addition, pretreatment with BDNF neutralizing
      antibody, but not control IgG abolished NRG1-induced increases in phospho-TrkB
      and phospho-NR2B levels. Moreover, studies using TrkB mutants showed that
      intercellular domain of TrkB is necessary for TrkB-ErbB4 interaction and NR2B
      activation. CONCLUSIONS: BDNF/TrkB signaling plays an important role in the NRG1
      stimulated NR2B regulation. These findings could be of relevance to many
      neurodevelopmental disorders, as NRG1 and BDNF signaling pathways have been
      implicated in autism and schizophrenia.

PMID- 25052838
TI  - Regulation and actions of activin A and follistatin in myocardial ischaemia
      reperfusion injury.
AB  - Activin A, a member of the transforming growth factor-beta superfamily, is
      stimulated early in inflammation via the Toll-like receptor (TLR) 4 signalling
      pathway, which is also activated in myocardial ischaemia-reperfusion.
      Neutralising activin A by treatment with the activin-binding protein,
      follistatin, reduces inflammation and mortality in several disease models. This
      study assesses the regulation of activin A and follistatin in a murine myocardial
      ischaemia-reperfusion model and determines whether exogenous follistatin
      treatment is protective against injury. Myocardial activin A and follistatin
      protein levels were elevated following 30 min of ischaemia and 2h of reperfusion
      in wild-type mice. Activin A, but not follistatin, gene expression was also up
      regulated. Serum activin A did not change significantly, but serum follistatin
      decreased. These responses to ischaemia-reperfusion were absent in TLR4(-/-)
      mice. Pre-treatment with follistatin significantly reduced ischaemia-reperfusion
      induced myocardial infarction. In mouse neonatal cardiomyocyte cultures, activin
      A exacerbated, while follistatin reduced, cellular injury after 3h of hypoxia and
      2h of re-oxygenation. Neither activin A nor follistatin affected hypoxia
      reoxygenation induced reactive oxygen species production by these cells. However,
      activin A reduced cardiomyocyte mitochondrial membrane potential, and follistatin
      treatment ameliorated the effect of hypoxia-reoxygenation on cardiomyocyte
      mitochondrial membrane potential. Taken together, these data indicate that
      myocardial ischaemia-reperfusion, through activation of TLR4 signalling,
      stimulates local production of activin A, which damages cardiomyocytes
      independently of increased reactive oxygen species. Blocking activin action by
      exogenous follistatin reduces this damage.

PMID- 25052839
TI  - Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role
      for neuroinflammation?
AB  - Vibratory angioedema is a rare form of physical urticaria, hereditary or
      acquired, which occurs at body sites exposed to vibrations. Pathogenic mechanisms
      of disease are not completely clear and, consequently, current pharmacological
      treatment is sometimes unsatisfactory. We report the case of a horn player
      affected by acquired vibratory angioedema, relapsing after prolonged use of the
      instrument and resistant to systemic antihistamines and corticosteroids, which
      successfully responded to therapy with low doses of amitriptyline and bromazepam.
      A neuroinflammatory mechanism can be likely implicated in the pathogenesis of
      vibratory angioedema, in line with many different cutaneous/mucosal diseases
      involving a complex interplay of homeostatic/allostatic systems. Furthermore, in
      mucosal diseases, such as vibratory angioedema, physical/psychological stressors
      have a relevant role. In such cases, because of the complex interplay between
      nervous and immune system, the pharmacological activity of benzodiazepines and
      typical antidepressants may downregulate neuroinflammation.

PMID- 25052841
TI  - Apelin is transcriptionally regulated by ER stress-induced ATF4 expression via a
      p38 MAPK-dependent pathway.
AB  - Apelin, which is an endogenous ligand for the orphan G-protein-coupled receptor
      APJ, was reported to be up-regulated by hypoxia-inducible factor 1-alpha (HIF1
      alpha) in hypoxia- and insulin-treated cell systems. However, a negative
      transcriptional regulator of apelin has not yet been identified. In this study,
      we showed that apelin is down-regulated by ATF4 via the pro-apoptotic p38 MAPK
      pathway under endoplasmic reticulum (ER) stress. First, we analyzed the human
      apelin promoter to characterize the effects of ER stress on apelin expression in
      hepatocytes. Treatment with thapsigargin, an inducer of ER stress, and over
      expression of ATF4 decreased apelin expression in hepatocytes. This work
      identified an ATF4-responsive region within the apelin promoter. Interestingly,
      ATF4-mediated repression of apelin was dependent upon the N-terminal domain of
      ATF4. C/EBP-beta knockdown experiments suggest that C/EBP-beta, which acts as an
      ATF4 binding partner, is critical for the ER stress-induced down-regulation of
      apelin. We also demonstrated that ATF4 regulates apelin gene expression via p38
      pathways. Ectopic expression of constitutively active MKK6, an upstream kinase of
      p38, suggested that activation of the p38 pathway is sufficient to induce ATF4
      mediated repression of apelin. Moreover, apelin enhanced cell migration in a
      wound healing assay in a p38 MAPK-dependent manner. Furthermore, analysis of
      caspase-3 activation indicated that ATF4 knockdown up-regulated apelin
      expression, leading to the inability of MKK6 (CA) to exert pro-apoptotic effects.
      Taken together, our results suggest that ATF4-mediated repression of apelin
      contributes substantially to the pro-apoptotic effects of p38. 

PMID- 25052842
TI  - The sodium pumping NADH:quinone oxidoreductase (Na+-NQR), a unique redox-driven
      ion pump.
AB  - The Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) is a unique Na(+)
      pumping respiratory complex found only in prokaryotes, that plays a key role in
      the metabolism of marine and pathogenic bacteria, including Vibrio cholerae and
      other human pathogens. Na(+)-NQR is the main entrance for reducing equivalents
      into the respiratory chain of these bacteria, catalyzing the oxidation of NADH
      and the reduction of quinone, the free energy of this redox reaction drives the
      selective translocation of Na(+) across the cell membrane, which energizes key
      cellular processes. In this review we summarize the unique properties of Na(+)
      NQR in terms of its redox cofactor composition, electron transfer reactions and a
      possible mechanism of coupling and pumping. 

PMID- 25052843
TI  - Intromitochondrial IkappaB/NF-kappaB signaling pathway is involved in amyloid
      beta peptide-induced mitochondrial dysfunction.
AB  - Mitochondrial dysfunction is a hallmark of amyloid beta peptide (Abeta)-induced
      neuronal toxicity in Alzheimer's disease (AD). However, the underlying mechanism
      (s) of Abeta-induced mitochondrial dysfunction is still not fully understood.
      There is evidence that nuclear factor-kappaB (NF-kappaB) is involved in Abeta
      induced neurotoxicity and is present in mitochondria. Using HT22 murine
      hippocampal neuronal cells and isolated mitochondria, the present study
      investigated whether intramitochondrial inhibitor of NF-kappaB (IkappaB)/NF
      kappaB signaling pathway was involved in mitochondrial dysfunction induced by
      Abeta. It was found that Abeta impaired mitochondrial function through a NF
      kappaB-dependent signaling pathway. Intramitochondrial IkappaBalpha/NF-kappaB
      pathway, induced by Abeta, decreased the expression of cytochrome c oxidase
      subunit (COXIII) and inhibited COX activity. These results provide new insights
      into the mechanism underlying the neurotoxic effect of Abeta and open up new
      therapeutic perspectives for AD. 

PMID- 25052844
TI  - Development of a novel iPad-based laparoscopic trainer and comparison with a
      standard laparoscopic trainer for basic laparoscopic skills testing.
AB  - INTRODUCTION: We developed the iTrainer (iT) as a portable laparoscopic trainer,
      which incorporates the iPad tablet. We then compared the iT with a standard
      pelvic trainer (SPT) to assess surgical skills as well as its image quality,
      resolution, brightness, comfort, and overall performance. MATERIALS AND METHODS:
      We designed and constructed the iT to be compatible with the Apple iPad 3 and
      standard laparoscopic instruments. Participants were assigned to perform the
      thread-the-loops task on both trainers and were prospectively randomized to start
      on either the iT or the SPT. Each participant was allowed a 2-minute warm-up
      before the 2-minute testing period. We scored participants using the product of
      skill quality (0-4 scale) and quantity of loops threaded (0-10 scale).
      Participants then rated each trainer on image quality, resolution, brightness,
      comfort, and overall performance on a 5-point Likert scale. RESULTS: A total of
      45 subjects including 10 undergraduates, 10 medical students, 10 general surgery
      and urology residents, and 15 experts (fellows and attending surgeons)
      participated in this study. There was no significant difference between thread
      the-loops task scores completed on the iT when compared with the SPT for all
      groups tested (p > 0.05) with the exception of the medical student group, who
      performed better on the SPT (p < 0.05). On evaluation of each trainer,
      participants rated the iT as having superior image quality and resolution when
      compared with the SPT (p < 0.05) but rated the SPT higher in overall performance
      (p < 0.05). Brightness and comfort were rated similarly for both trainers.
      CONCLUSIONS: We have demonstrated face validity and criterion validity for the
      thread-the-loops task on the iT. The iT rated superior in image quality and
      resolution but inferior in overall performance compared with the SPT. The iT
      provides trainees a unique advantage over SPT as an additional resource to
      laparoscopic training as it is inexpensive, portable, and can be readily
      available for training.

PMID- 25052845
TI  - Ovipositor morphology of cosmetid harvestmen (Arachnida, Opiliones, Laniatores):
      a new source of informative characters.
AB  - The external morphology of the penis is an important source of systematic
      characters in phylogenetic studies of harvestmen. Modern taxonomic studies
      generally include micrographs generated by scanning electron microscopy (SEM) to
      illustrate penis morphology. In contrast, the external morphology of the
      ovipositor has largely been ignored for harvestmen belonging to the suborder
      Laniatores. Comparative studies of ovipositor microanatomy using SEM are
      especially lacking for species belonging to the superfamily Gonyleptoidea. In an
      effort to determine if the ovipositor could be a useful source of informative
      characters for these harvestmen, we investigated interspecific variation in the
      external morphology of the ovipositor for 14 species from the family Cosmetidae.
      Our SEM-based study revealed that the external surface of the distal tips of the
      ovipositors of most species was generally divided into four symmetrical lobes,
      although we observed a bilobed condition in Erginulus clavotibialis and Erginulus
      subserialis. The distal surfaces were also generally smooth, with the exception
      of the ovipositor of Erginulus weyerensis, which featured small surface setae. In
      addition, we observed considerable interspecific variation in the morphology of
      the peripheral setae on the distal tip, especially with respect to relative size,
      morphology of the shaft, and number, symmetry, and shapes of the distal tips. The
      functional significance, if any, of variation in the structure of the peripheral
      setae is unclear. Additional behavioral studies of copulation and oviposition are
      needed to determine the functional relationships between reproductive morphology
      and behavior. The morphological variation that we observed suggests that future
      taxonomic studies of cosmetid harvestmen, and potentially other gonyleptoidean
      taxa, would benefit from the inclusion of descriptions of ovipositor morphology.

PMID- 25052846
TI  - Do people with intellectual disability use Nintendo Wii when placed in their home
      as part of a physiotherapy program? An observational study.
AB  - PURPOSE: To examine how much, and in what way, Nintendo WiiTM (Wii) is used when
      prescribed as part of a home-physiotherapy program for people with intellectual
      disability. METHODS: Twenty people with intellectual disability were recruited.
      The following parameters were recorded about play patterns over a 12-week period:
      frequency, duration, perceived exertion, play position, play mode, initiation of
      play and games from Wii Sports and Wii Fit Plus. RESULTS: Participants used the
      Wii for a median of 101 min per week (interquartile range [IQR]: 50-172) in weeks
      one and two across a median of three days per week (IQR: 3-4), decreasing down to
      a median of 35 min per week (IQR: 0-141) in weeks 11 and 12 across a median of
      one day per week (IQR: 0-3). CONCLUSIONS: Usage of the Wii drops off rapidly when
      it is placed in the homes of people with intellectual disability as part of a
      physiotherapy program. Implications for Rehabilitation Usage of the Nintendo Wii
      drops off rapidly when it is placed in the homes of people with intellectual
      disability and they are instructed to use it as part of a home physiotherapy
      program. Games commonly played include bowling and boxing in Wii Sport, and
      penguin slide, ski jump and tight rope walk in Wii Fit Plus. Physiotherapists
      should use person and family centred practice to ensure that Nintendo Wii is a
      suitable intervention for the person with an intellectual disability and provide
      support to encourage ongoing usage.

PMID- 25052848
TI  - Melanocyte migration is influenced by E-cadherin-dependent adhesion of
      keratinocytes in both two- and three-dimensional in vitro wound models.
AB  - During wound healing, melanocytes are required to migrate into the wounded area
      that is still in the process of re-construction. The role and behaviour of
      melanocytes during this process is poorly understood, that is, whether melanocyte
      migration into the wound is keratinocyte-dependent or not. This paper attempts,
      through the use of both two- and three-dimensional in vitro models, to understand
      the role and behaviour of melanocytes during the process of wound healing. In
      addition, it sheds light on whether keratinocytes influence/contribute toward
      melanocyte migration and ultimately wound healing. Scratch assays were performed
      to analyse migration and Western blot analyses measured cellular E-cadherin
      expression. Immunohistochemistry was used to analyse the in vivo 3D wound healing
      effect. Scratch assays performed on co-cultures of melanocytes and keratinocytes
      demonstrated that melanocytes actively migrated, with the use of their dendrites,
      into the scratch ahead of the proliferating keratinocyte sheet. Migration of the
      melanocyte into the wound bed was accompanied by loss of attachment to
      keratinocytes at the wound front with concomitant downregulation of E-cadherin
      expression as observed through immunocytochemistry. This result suggests that, in
      vitro, melanocyte migration occurs independently of keratinocytes but that the
      migration is influenced by keratinocyte E-cadherin expression. We now demonstrate
      that melanocyte migration during re-pigmentation is an active process, and
      suggest that targeting of mechanisms involved in active melanocyte migration
      (e.g. the melanocyte dendrite) may enhance the re-pigmentation process. 

PMID- 25052847
TI  - Melatonin analgesia is associated with improvement of the descending endogenous
      pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy,
      controlled trial.
AB  - BACKGROUND: Central disinhibition is a mechanism involved in the physiopathology
      of fibromyalgia. Melatonin can improve sleep quality, pain and pain threshold. We
      hypothesized that treatment with melatonin alone or in combination with
      amitriptyline would be superior to amitriptyline alone in modifying the
      endogenous pain-modulating system (PMS) as quantified by conditional pain
      modulation (CPM), and this change in CPM could be associated with serum brain
      derived neurotrophic factor (BDNF). We also tested whether melatonin improves the
      clinical symptoms of pain, pain threshold and sleep quality. METHODS: Sixty-three
      females, aged 18 to 65, were randomized to receive bedtime amitriptyline (25 mg)
      (n = 21), melatonin (10 mg) (n = 21) or melatonin (10 mg) + amitriptyline (25 mg)
      (n = 21) for a period of six weeks. The descending PMS was assessed with the CPM
      TASK. It was assessed the pain score on the Visual Analog Scale (VAS 0-100 mm),
      the score on Fibromyalgia Impact Questionnaire (FIQ), heat pain threshold (HPT),
      sleep quality and BDNF serum. Delta values (post- minus pre-treatment) were used
      to compare the treatment effect. The outcomes variables were collected before,
      one and six weeks after initiating treatment. RESULTS: Melatonin alone or in
      combination with amitriptyline reduced significantly pain on the VAS compared
      with amitriptyline alone (P < 0.01). The delta values on the VAS scores were
      12.85 (19.93),-17.37 (18.69) and-20.93 (12.23) in the amitriptyline, melatonin
      and melatonin+amitriptyline groups, respectively. Melatonin alone and in
      combination increased the inhibitory PMS as assessed by the Numerical Pain Scale
      [NPS(0-10)] reduction during the CPM-TASK:-2.4 (2.04) melatonin + amitriptyline,
      2.65 (1.68) melatonin, and-1.04 (2.06) amitriptyline, (P < 0.05). Melatonin +
      amitriptyline treated displayed better results than melatonin and amitriptyline
      alone in terms of FIQ and PPT improvement (P < 0.05, fort both). CONCLUSION:
      Melatonin increased the inhibitory endogenous pain-modulating system as assessed
      by the reduction on NPS(0-10) during the CPM-TASK. Melatonin alone or associated
      with amitriptyline was better than amitriptyline alone in improving pain on the
      VAS, whereas its association with amitriptyline produced only marginal additional
      clinical effects on FIQ and PPT. TRIAL REGISTRATION: Current controlled trail is
      registered at clinical trials.gov upon under number NCT02041455. Registered
      January 16, 2014.

PMID- 25052849
TI  - AE37 peptide vaccination in prostate cancer: identification of biomarkers in the
      context of prognosis and prediction.
AB  - A fundamental challenge in administering immunotherapies for cancer is the
      establishment of biomarkers that can predict patients' responsiveness to
      treatment. In this study, our aim was to predict the immunologic and clinical
      responses of vaccination therapy with an Ii-key-modified HER-2/neu peptide (Ii
      key/HER-2(776-790) or AE37), applied in our recent phase I study in patients with
      prostate cancer. To this end, we retrospectively analyzed our data derived from
      immunologic determinations before, during and after primary series of
      vaccinations with AE37, as well as after one AE37 booster injection. Using the
      obtained data, we then observed the relationship between the immunologic
      parameters and clinical outcome of patients. We found that preexisting levels of
      transforming growth factor beta (TGF-beta) had an inverse correlation with in
      vivo and in vitro immunologic responses to the AE37 vaccine which were measured
      as delayed-type hypersensitivity (DTH) and interferon gamma (IFN-gamma)
      production in response to the native HER-2(776-790) (or AE36) peptide,
      respectively. Patients with preexistent IFN-gamma immunity to AE36 developed
      positive DTH reactions after primary vaccinations and booster. Moreover, we could
      detect a direct correlation between IFN-gamma production and DTH reactions in
      response to AE36 challenge in our vaccinated patients. DTH reactions were a
      stronger indicator for patients' overall survival (OS) than preexistent or
      vaccine-induced IFN-gamma immunity. In contrast, we found that preexisting TGF
      beta levels were correlated with shorter patients' OS. These retrospective
      analyses suggest that the above biomarkers at the time-points measured offer
      promise for evaluating immunologic and clinical responses to AE37-based
      vaccinations. 

PMID- 25052850
TI  - Effect of home-based counselling on newborn care practices in southern Tanzania
      one year after implementation: a cluster-randomised controlled trial.
AB  - BACKGROUND: In Sub-Saharan Africa over one million newborns die annually. We
      developed a sustainable and scalable home-based counselling intervention for
      delivery by community volunteers in rural southern Tanzania to improve newborn
      care practices and survival. Here we report the effect on newborn care practices
      one year after full implementation. METHODS: All 132 wards in the 6-district
      study area were randomised to intervention or comparison groups. Starting in
      2010, in intervention areas trained volunteers made home visits during pregnancy
      and after childbirth to promote recommended newborn care practices including
      hygiene, breastfeeding and identification and extra care for low birth weight
      babies. In 2011, in a representative sample of 5,240 households, we asked women
      who had given birth in the previous year both about counselling visits and their
      childbirth and newborn care practices. RESULTS: Four of 14 newborn care practices
      were more commonly reported in intervention than comparison areas: delaying the
      baby's first bath by at least six hours (81% versus 68%, OR 2.0 (95% CI 1.2
      3.4)), exclusive breastfeeding in the three days after birth (83% versus 71%, OR
      1.9 (95% CI 1.3-2.9)), putting nothing on the cord (87% versus 70%, OR 2.8 (95%
      CI 1.7-4.6)), and, for home births, tying the cord with a clean thread (69%
      versus 39%, OR 3.4 (95% CI 1.5-7.5)). For other behaviours there was little
      evidence of differences in reported practices between intervention and comparison
      areas including childbirth in a health facility or with a skilled attendant,
      thermal care practices, breastfeeding within an hour of birth and, for home
      births, the birth attendant having clean hands, cutting the cord with a clean
      blade and birth preparedness activities. CONCLUSIONS: A home-based counselling
      strategy using volunteers and designed for scale-up can improve newborn care
      behaviours in rural communities of southern Tanzania. Further research is needed
      to evaluate if, and at what cost, these gains will lead to improved newborn
      survival. TRIAL REGISTRATION: Trial Registration Number NCT01022788
      (http://www.clinicaltrials.gov, 2009).

PMID- 25052851
TI  - Gamma secretase-activating protein is a substrate for caspase-3: implications for
      Alzheimer's disease.
AB  - BACKGROUND: A major feature of Alzheimer's disease (AD) is the accumulation of
      amyloid-beta (Abeta), whose formation is regulated by the gamma-secretase complex
      and its activating protein (also known as GSAP). Because GSAP interacts with
      gamma-secretase without affecting the cleavage of Notch, it is an ideal target
      for a viable anti-Abeta therapy. However, despite much interest in this protein,
      the mechanisms involved in its neurobiology are unknown. METHODS: Postmortem
      brain tissue samples from AD patients, transgenic mouse models of AD, and
      neuronal cells were used to investigate the molecular mechanism involved in GSAP
      formation and subsequent amyloidogenesis. RESULTS: We identified a caspase-3
      processing domain in the GSAP sequence and provide experimental evidence that
      this caspase is essential for GSAP activation and biogenesis of Abeta peptides.
      Furthermore, we demonstrated that caspase-3-dependent GSAP formation occurs in
      brains of individuals with AD and two different mouse models of AD and that the
      process is biologically relevant because its pharmacological blockade reduces
      Abeta pathology in vivo. CONCLUSIONS: Our data, by identifying caspase-3 as the
      endogenous modulator of GSAP and Abeta production, establish caspase-3 as a
      novel, attractive and viable Abeta-lowering therapeutic target for AD.

PMID- 25052852
TI  - A chaperone enhances blood alpha-glucosidase activity in Pompe disease patients
      treated with enzyme replacement therapy.
AB  - Enzyme replacement therapy is currently the only approved treatment for Pompe
      disease, due to acid alpha-glucosidase deficiency. Clinical efficacy of this
      approach is variable, and more effective therapies are needed. We showed in
      preclinical studies that chaperones stabilize the recombinant enzyme used for
      enzyme replacement therapy. Here, we evaluated the effects of a combination of
      enzyme therapy and a chaperone on alpha-glucosidase activity in Pompe disease
      patients. alpha-Glucosidase activity was analyzed by tandem-mass spectrometry in
      dried blood spots from patients treated with enzyme replacement therapy, either
      alone or in combination with the chaperone N-butyldeoxynojirimycin given at the
      time of the enzyme infusion. Thirteen patients with different presentations (3
      infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination
      treatment resulted in alpha-glucosidase activities greater than 1.85-fold the
      activities with enzyme replacement therapy alone. In the whole patient
      population, alpha-glucosidase activity was significantly increased at 12 hours
      (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold,
      P = 0.003). The areas under the curve were also significantly increased (6.78
      fold, P = 0.002). These results suggest improved stability of recombinant alpha
      glucosidase in blood in the presence of the chaperone. 

PMID- 25052853
TI  - Geranyllinalool synthases in solanaceae and other angiosperms constitute an
      ancient branch of diterpene synthases involved in the synthesis of defensive
      compounds.
AB  - Many angiosperm plants, including basal dicots, eudicots, and monocots, emit
      (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene, which is derived from
      geranyllinalool, in response to biotic challenge. An Arabidopsis (Arabidopsis
      thaliana) geranyllinalool synthase (GLS) belonging to the e/f clade of the
      terpene synthase (TPS) family and two Fabaceae GLSs that belong to the TPS-g
      clade have been reported, making it unclear which is the main route to
      geranyllinalool in plants. We characterized a tomato (Solanum lycopersicum) TPS
      e/f gene, TPS46, encoding GLS (SlGLS) and its homolog (NaGLS) from Nicotiana
      attenuata. The Km value of SlGLS for geranylgeranyl diphosphate was 18.7 um, with
      a turnover rate value of 6.85 s(-1). In leaves and flowers of N. attenuata, which
      constitutively synthesize 17-hydroxygeranyllinalool glycosides, NaGLS is
      expressed constitutively, but the gene can be induced in leaves with methyl
      jasmonate. In tomato, SlGLS is not expressed in any tissue under normal growth
      but is induced in leaves by alamethicin and methyl jasmonate treatments. SlGLS,
      NaGLS, AtGLSs, and several other GLSs characterized only in vitro come from four
      different eudicot families and constitute a separate branch of the TPS-e/f clade
      that diverged from kaurene synthases, also in the TPS-e/f clade, before the
      gymnosperm-angiosperm split. The early divergence of this branch and the GLS
      activity of genes in this branch in diverse eudicot families suggest that GLS
      activity encoded by these genes predates the angiosperm-gymnosperm split.
      However, although a TPS sequence belonging to this GLS lineage was recently
      reported from a basal dicot, no representative sequences have yet been found in
      monocot or nonangiospermous plants. 

PMID- 25052854
TI  - Long-term evolution of nucleotide-binding site-leucine-rich repeat genes:
      understanding gained from and beyond the legume family.
AB  - Proper utilization of plant disease resistance genes requires a good
      understanding of their short- and long-term evolution. Here we present a
      comprehensive study of the long-term evolutionary history of nucleotide-binding
      site (NBS)-leucine-rich repeat (LRR) genes within and beyond the legume family.
      The small group of NBS-LRR genes with an amino-terminal RESISTANCE TO POWDERY
      MILDEW8 (RPW8)-like domain (referred to as RNL) was first revealed as a basal
      clade sister to both coiled-coil-NBS-LRR (CNL) and Toll/Interleukin1 receptor-NBS
      LRR (TNL) clades. Using Arabidopsis (Arabidopsis thaliana) as an outgroup, this
      study explicitly recovered 31 ancestral NBS lineages (two RNL, 21 CNL, and eight
      TNL) that had existed in the rosid common ancestor and 119 ancestral lineages
      (nine RNL, 55 CNL, and 55 TNL) that had diverged in the legume common ancestor.
      It was shown that, during their evolution in the past 54 million years,
      approximately 94% (112 of 119) of the ancestral legume NBS lineages experienced
      deletions or significant expansions, while seven original lineages were
      maintained in a conservative manner. The NBS gene duplication pattern was further
      examined. The local tandem duplications dominated NBS gene gains in the total
      number of genes (more than 75%), which was not surprising. However, it was
      interesting from our study that ectopic duplications had created many novel NBS
      gene loci in individual legume genomes, which occurred at a significant frequency
      of 8% to 20% in different legume lineages. Finally, by surveying the legume
      microRNAs that can potentially regulate NBS genes, we found that the microRNA-NBS
      gene interaction also exhibited a gain-and-loss pattern during the legume
      evolution. 

PMID- 25052855
TI  - Prevention of infectious diseases during military deployments: a review of the
      French armed forces strategy.
AB  - Military personnel in operations have always paid a high toll to infections. In
      the 21st century some of these diseases still cause outbreaks with significant
      morbidity and impact on deployments. The new configuration of the French Armed
      Forces requires the permanent preparedness of deployable units. During
      deployments, soldiers are at least exposed to the infectious diseases that are
      observed in travellers, but with a potentially severe impact for the combatting
      strengths and a risk for cancelation or failure of the operational durability.
      The most common disabling infections during military deployments are faeco-oral
      transmitted diseases including diarrhoea. Preventing infectious diseases during
      deployments is of great concern and the French medical service has established a
      strategy based on different components; risk assessment and preparation,
      immunizations, protective measures and chemoprophylaxis, health education, health
      surveillance, outbreak investigations and medical tracking. In this review, the
      authors present the context of deployment of the French Armed Forces, the main
      health risks they are exposed to and develop the key points of the force health
      protection strategy, focused on infections related to military deployments. 

PMID- 25052856
TI  - Managing sedentary behavior to reduce the risk of diabetes and cardiovascular
      disease.
AB  - Modern human environments are vastly different from those of our forebears.
      Rapidly advancing technology in transportation, communications, workplaces, and
      home entertainment confer a wealth of benefits, but increasingly come with costs
      to human health. Sedentary behavior-too much sitting as distinct from too little
      physical activity-contributes adversely to cardiometabolic health outcomes and
      premature mortality. Findings from observational epidemiology have been
      synthesized in meta-analyses, and evidence is now shifting into the realm of
      experimental trials with the aim of identifying novel mechanisms and potential
      causal relationships. We discuss recent observational and experimental evidence
      that makes a compelling case for reducing and breaking up prolonged sitting time
      in both the primary prevention and disease management contexts. We also highlight
      future research needs, the opportunities for developing targeted interventions,
      and the potential of population-wide initiatives designed to address too much
      sitting as a health risk.

PMID- 25052857
TI  - Fetal growth reference ranges in twin pregnancy: analysis of the Southwest Thames
      Obstetric Research Collaborative (STORK) multiple pregnancy cohort.
AB  - OBJECTIVE: To generate reference charts for expected fetal growth in dichorionic
      diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies and to
      compare these with those from singleton pregnancies. METHODS: This was a
      retrospective study of biometric measurements from serial ultrasound examinations
      of twin pregnancies in the second and third trimesters, from 14 weeks' gestation
      to term, collected by nine hospitals over a 10-year period. The measurements
      obtained in each fetus at each examination included head circumference (HC),
      biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL).
      Multilevel mixed effects statistical models were used to evaluate growth in each
      biometric variable in relation to gestational age, taking account of the serial
      examinations and the association between the two fetuses in each pregnancy, with
      separate models constructed for DCDA and MCDA pregnancies. RESULTS: The final
      dataset for analysis included a total of 9866 second- and third-trimester
      ultrasound examinations in 1802 DCDA and 323 MCDA twin pregnancies, with a median
      of five (range, 1-14) scans per pregnancy. For each variable, the mean value for
      DCDA twins was close to the reported value in singletons at 20-30 weeks and
      showed a decrease relative to singletons beyond 30 weeks. The differences were
      greater for AC and HC, for which the mean in twins was approximately equivalent
      to the 30th percentile in singletons at 18 weeks, the 35th percentile at 25 weeks
      and the 30th percentile at 35 weeks. Fetuses in MCDA twin pregnancies displayed
      lower mean measurements than did those in DCDA pregnancies throughout the
      gestational age range considered. CONCLUSIONS: Ultrasound biometry shows a small
      but statistically significant reduction in fetal growth in twin pregnancies
      relative to that in singletons, particularly in the third trimester, with a more
      marked difference for MCDA than for DCDA pregnancies.

PMID- 25052858
TI  - The variable phenotypes of KCNQ-related epilepsy.
AB  - Mutations in KCNQ2 and KCNQ3 were originally described in infants with benign
      familial neonatal seizures (BFNS). Recently, KCNQ2 mutations have also been shown
      to cause epileptic encephalopathy. This report describes three infants carrying
      abnormalities of KCNQ2 and one infant with a KCNQ3 mutation. The different KCNQ2
      abnormalities led to different phenotypes and included a novel intragenic
      duplication, c.419_430dup, in an infant with BFNS, a 0.761Mb 20q13.3 contiguous
      gene deletion in an infant with seizures at 3 months, and a recurrent de novo
      missense mutation c.881C>T in a neonate with "KCNQ2-encephalopathy." The mutation
      in KCNQ3, c.989G>A, was novel and occurred in an infant with BFNS. KCNQ-related
      seizures often present with tonic/clonic manifestations, cyanosis, or apnea.
      Certain genotype-phenotype correlations help predict outcome. Similarly affected
      family members suggests benign familial "KCNQ-related" epilepsy, whereas neonatal
      seizures with unexplained multifocal epileptiform discharges or burst suppression
      on electroencephalography, and acute abnormalities of the basal ganglia/thalami
      are suggestive of KCNQ2-encephalopathy, which is often sporadic. 20q13.33
      contiguous gene deletion encompassing KCNQ2 may harbor atypical features
      depending on deletion size. Although the phenotype often guides direct targeted
      gene testing in these conditions, array CGH should also be considered in
      suspected sporadic or atypical familial cases to diagnose 20q13.33 deletion.

PMID- 25052859
TI  - How popular is waterpipe tobacco smoking? Findings from internet search queries.
AB  - OBJECTIVES: Waterpipe tobacco smoking (WTS), a traditional tobacco consumption
      practice in the Middle East, is gaining popularity worldwide. Estimates of
      population-level interest in WTS over time are not documented. We assessed the
      popularity of WTS using World Wide Web search query results across four English
      speaking countries. METHODS: We analysed trends in Google search queries related
      to WTS, comparing these trends with those for electronic cigarettes between 2004
      and 2013 in Australia, Canada, the UK and the USA. Weekly search volumes were
      reported as percentages relative to the week with the highest volume of searches.
      RESULTS: Web-based searches for WTS have increased steadily since 2004 in all
      four countries. Search volume for WTS was higher than for e-cigarettes in three
      of the four nations, with the highest volume in the USA. Online searches were
      primarily targeted at WTS products for home use, followed by searches for WTS
      cafes/lounges. CONCLUSIONS: Online demand for information on WTS-related products
      and venues is large and increasing. Given the rise in WTS popularity, increasing
      evidence of exposure-related harms, and relatively lax government regulation, WTS
      is a serious public health concern and could reach epidemic levels in Western
      societies.

PMID- 25052860
TI  - Promoting cessation resources through cigarette package warning labels: a
      longitudinal survey with adult smokers in Canada, Australia and Mexico.
AB  - INTRODUCTION: Health warning labels (HWLs) on tobacco packaging can be used to
      provide smoking cessation information, but the impact of this information is not
      well understood. METHODS: Online consumer panels of adult smokers from Canada,
      Australia and Mexico were surveyed in September 2012, January 2013 and May 2013;
      replenishment was used to maintain sample sizes of 1000 participants in each
      country at each wave. Country-stratified logistic Generalised Estimating Equation
      (GEE) models were estimated to assess correlates of citing HWLs as a source of
      information on quitlines and cessation websites. GEE models also regressed having
      called the quitline, and having visited a cessation website, on awareness of
      these resources because of HWLs. RESULTS: At baseline, citing HWLs as a source of
      information about quitlines was highest in Canada, followed by Australia and
      Mexico (33%, 19% and 16%, respectively). Significant increases over time were
      only evident in Australia and Mexico. In all countries, citing HWLs as a source
      of quitline information was significantly associated with self-report of having
      called a quitline. At baseline, citing HWLs as a source of information about
      cessation websites was higher in Canada than in Australia (14% and 6%,
      respectively; Mexico was excluded because HWLs do not include website
      information), but no significant changes over time were found for either country.
      Citing HWLs as a source of information about cessation websites was significantly
      associated with having visited a website in both Canada and Australia.
      CONCLUSIONS: HWLs are an important source of cessation information.

PMID- 25052861
TI  - Tobacco industry marketing: an analysis of direct mail coupons and giveaways.
AB  - BACKGROUND: Despite marketing prohibitions, tobacco company marketing
      expenditures in the USA have continued to grow with tobacco companies shifting
      focus towards point-of-sale-marketing and direct marketing to consumers through
      the mail and on the web. The purpose of this observational study was to
      investigate the content of direct marketing sent in response to registrations on
      select industry websites. METHODS: An analysis of 659 tobacco company direct mail
      marketing pieces received between July 2011 and June 2012 was conducted. Mailings
      were coded for type and value of tobacco coupons, type of tobacco products
      promoted with coupons and number and type of giveaways offered. RESULTS: The most
      common type of mailing was tobacco coupon distribution; 86.5% of the mailings
      contained at least one coupon. Mailings with coupons had an average estimated
      coupon value of $4.17. The total coupon value of each mailing varied by the type
      of coupon offer and product promoted. The Camel and Marlboro coupon mailings
      heavily promoted snus, with over half of Camel coupon mailings (60.9%) and nearly
      half (44.8%) of Marlboro coupon mailings promoting snus alone. In addition, 47.9%
      of Marlboro coupon mailings and 11.4% of Camel mailings promoted snus alongside
      cigarettes. DISCUSSION: Tobacco companies use direct mail marketing to
      communicate with consumers and provide valuable tobacco coupons. More research is
      needed to understand the content of these mailings and how they are used by
      tobacco consumers in order to develop effective policy solutions.

PMID- 25052862
TI  - Predicting decreases in smoking with a cigarette purchase task: evidence from an
      excise tax rise in New Zealand.
AB  - BACKGROUND: Tobacco excise taxes are known to be effective in reducing smoking at
      the population level, but less research has examined how individual smokers
      respond to changes in tax policy. We ask whether price elasticities for
      individual smokers, derived from simulated demand curves obtained with a
      cigarette purchase task (CPT), can predict changes in smoking after a tax
      increase. METHOD: Smokers (N=357) were recruited from four New Zealand cities and
      interviewed before and after a 10% tobacco excise tax increase. RESULTS:
      Simulated demand curves from the CPT were curvilinear and well described by an
      exponential model. Smokers reported significant reductions in cigarettes/day and
      addiction scores at Wave 2 (n=226). Local elasticities derived from the demand
      curves significantly predicted decreases in cigarettes/day after controlling for
      covariates. CONCLUSIONS: Elasticities from simulated demand curves can predict
      decreases in consumption for individual smokers after an excise tax increase.
      Understanding individual differences in tobacco demand curves may help to predict
      how different groups of smokers will respond to price increases.

PMID- 25052863
TI  - Transparency as a remedy against racketeering: preventing and restraining fraud
      by exposing Big Tobacco's dirty secrets.
AB  - The 1990s state litigation that resulted in the tobacco industry's initial
      document disclosure obligations fully expired in 2010. These obligations have
      been extended and enhanced until 2021 through a federal lawsuit against the
      tobacco industry over violations of the Racketeer Influenced Corrupt
      Organizations Act (RICO). In this special communication, we summarise and explain
      the new legal framework and enhanced document disclosure obligations of the major
      US tobacco companies. We describe the events leading up to these new
      requirements, including the tobacco companies' failed attempt to close the
      Minnesota Tobacco Document Depository, the release of 100 000 documents onto the
      companies' document websites discovered to have been publicly available at the
      Minnesota Tobacco Document Depository but not online, and the addition of over
      2300 documents to those websites, which are also now publicly available at
      Minnesota after being secured for years in a separate, non-public storage room at
      the Minnesota Tobacco Document Depository. We also detail the document indexing
      enhancements and redesign of the University of California, San Francisco's Legacy
      Tobacco Documents Library website, made possible by the RICO litigation, and
      which is anticipated to be released in September 2014. Last, we highlight the
      public health community's continued opportunity to expose the US tobacco
      industry's efforts to undermine public health through these new search
      enhancements and improved document accessibility and due to the continuously
      growing document collection until at least 2021. 

PMID- 25052864
TI  - Comparison of secondhand smoke exposure measures during pregnancy in the
      development of a clinical prediction model for small-for-gestational-age among
      non-smoking Chinese pregnant women.
AB  - OBJECTIVE: To compare predictive values of small-for-gestational-age (SGA) by
      different measures for secondhand smoke (SHS) exposure during pregnancy and to
      develop and validate a prediction model for SGA using SHS exposure along with
      sociodemographic and pregnancy factors. METHODS: We compared the predictability
      of different measures of SHS exposure during pregnancy for SGA among 545 Chinese
      pregnant women, and then used the optimal SHS measure along with other clinically
      available factors to develop and validate a prediction model for SGA. We fit
      logistic regression models to predict SGA by single measures of SHS exposure
      (self-report, serum cotinine and CYP2A6*4) and different combinations (self
      report+cotinine, cotinine+CYP2A6*4, self-report+CYP2A6*4 and self
      report+cotinine+CYP2A6*4). RESULTS: We found that self-reported SHS exposure
      alone predicted SGA (area under the receiver operating characteristic curve or
      area under the receiver operating curve (AUROC), 0.578) better than the other two
      single measures (cotinine, 0.547; CYP2A6*4, 0.529) or as accurately as combined
      SHS measures (0.545-0.584). The final prediction model that contained self
      reported SHS exposure, prepregnancy body mass index, gestational weight gain
      velocity during the second and third trimesters, gestational diabetes,
      gestational hypertension and the third-trimester biparietal diameter Z-score
      could predict SGA fairly accurately (AUROC, 0.698). CONCLUSIONS: Self-reported
      SHS exposure at peribirth performs better in predicting SGA than a single measure
      of serum cotinine at the same time, although repeated biochemical cotinine
      assessments throughout pregnancy may be optimal. Our simple prediction model is
      fairly accurate and can be potentially used in routine prenatal care.

PMID- 25052865
TI  - Reversible multistep synthesis with equilibrium properties based on a selection
      oriented process with a repetitive sequence of steps.
AB  - Reversible processes and reactions exhibit equilibrium and error correction
      properties that allow them to surpass the limits of irreversible systems.
      However, such processes are currently limited to completely reversible one-pot
      transformations. In this work, we analyze and demonstrate a new system of
      reversible multistep syntheses that enable the introduction of reversibility and
      equilibrium properties, previously reserved for single-step processes, into step
      by-step synthesis transformations. The system uses a repetitive sequence of steps
      such that the same sequence of reactions is performed on the material again and
      again in a loop. The final step in each loop transforms unequal fractions of all
      products back to the starting material. We show that such a system is reversible,
      even if some steps in the synthesis are irreversible. We mathematically analyze
      and experimentally demonstrate the properties of such systems and show that they
      include many features unique to reversible and equilibrium systems. This approach
      can enable new methods for controlling the distribution of the products of
      chemical transformations. 

PMID- 25052866
TI  - Pharmacodynamic profile of commonly utilised parenteral therapies against
      meticillin-susceptible and meticillin-resistant Staphylococcus aureus collected
      from US hospitals.
AB  - Staphylococcus aureus is a well-recognised pathogen with an evolving phenotypic
      profile often limiting conventional beta-lactam use. In vitro potency and
      pharmacodynamic profile of commonly utilised agents against 1238 meticillin
      susceptible S. aureus (MSSA) and 1259 meticillin-resistant S. aureus (MRSA) from
      clinical specimens at 42 hospitals were assessed. Non-duplicate, non-urine
      isolates were tested by broth microdilution against cefazolin, ceftaroline,
      ceftriaxone, daptomycin, linezolid, nafcillin, tigecycline and vancomycin. Monte
      Carlo simulations were conducted using pharmacokinetic profiles from patients or
      volunteers to generate the probability of target attainment and determine the
      cumulative fraction of response (CFR), a modelling-based prediction tool of
      achieving pharmacokinetic/pharmacodynamic endpoints, for commonly used regimens.
      Of isolates tested, 62 MSSA (5.0%) were ceftriaxone-non-susceptible and 4 (0.3%)
      and 2 (0.2%) MRSA were ceftaroline- and daptomycin-non-susceptible, respectively.
      Against MSSA, cefazolin 1000 mg q8h and nafcillin 2000 mg q4h produced CFRs
      >=90%. For ceftriaxone, only 2000 mg q12h produced a CFR >=90%. Against MSSA and
      MRSA, ceftaroline, daptomycin, linezolid and tigecycline provided CFRs >=90%.
      Vancomycin produced similar CFRs against MSSA and MRSA. Vancomycin 1000 mg and 15
      mg/kg q8h produced CFRs of 91% and 93%, respectively, whilst q12h doses were
      <90%. Against respiratory and blood isolates or ICU isolates, only vancomycin q8h
      produced desired CFRs, where the MIC90 was 2 MUg/mL. These data suggest cefazolin
      and nafcillin produce high CFRs against MSSA, whilst ceftriaxone at common doses
      may no longer be suitable. Vancomycin q8h is needed to optimise CFRs.
      Ceftaroline, daptomycin, tigecycline and linezolid produced sufficiently high
      CFRs against MSSA and MRSA utilising approved regimens.

PMID- 25052867
TI  - Toxic epidermal necrolysis reaction associated with the use of moxifloxacin.

PMID- 25052868
TI  - Expansive spread of IncI1 plasmids carrying blaCMY-2 amongst Escherichia coli.
AB  - Escherichia coli is a leading cause of urinary tract infections. One of the most
      common antibiotic classes used to treat such infections is the beta-lactams,
      including cephalosporins. Resistance to the third-generation cephalosporins can
      be caused by production of extended-spectrum beta-lactamases (ESBLs) or plasmid
      mediated AmpC beta-lactamases. The most commonly reported AmpC beta-lactamase in
      E. coli is CMY-2. Plasmid-mediated CMY-2 has been frequently reported in E. coli
      and Salmonella sp. from food-producing animals. This study aimed to elucidate the
      molecular characteristics of clinical E. coli isolates carrying plasmids encoding
      CMY-2. A total of 67 CMY-2-producing E. coli were characterised by clonal
      analysis and phylogenetic typing. Characterisation of the plasmids carrying
      blaCMY-2 included replicon typing, plasmid profiling, plasmid transferability and
      sequencing of the blaCMY-2 genetic environment. As a result, E. coli producing
      CMY-2 was found to be highly polyclonal. The majority of CMY-2-producing E. coli
      belonged to phylogenetic group D. IncI1 plasmids were predominant among those
      carrying blaCMY-2 (96%). Restriction analysis revealed a single IncI1 plasmid
      carrying blaCMY-2 to be predominant and present in different clones of E. coli.
      IS1294-ISEcp1 complex or ISEcp1 that was truncated by IS1294 was the predominant
      insertion sequence upstream of blaCMY-2. The homogeneous genetic environment of
      blaCMY-2 observed among different strains of E. coli strongly suggests horizontal
      transfer of this IncI1, blaCMY-2-carrying plasmid. In summary, horizontal plasmid
      transfer plays a major role in the spread of blaCMY-2 in E. coli. 

PMID- 25052869
TI  - Association of quantity and duration of smoking with erectile dysfunction: a dose
      response meta-analysis.
AB  - INTRODUCTION: Some original studies and a recent meta-analysis suggested that
      smoking could be associated with the risk of erectile dysfunction (ED), but the
      dose-response relationship between them was unclear. AIM: The aim of this study
      was to investigate the potential association between quantity and duration of
      smoking and the risk of ED. METHODS: We conducted a literature search of PubMed,
      Embase, Web of Science, and Scopus from these databases' inception through March
      2014 for observational epidemiological studies examining the association between
      smoking and risk of ED. Random-effects meta-analyses were used to combine the
      results of included studies. MAIN OUTCOME MEASURE: Quantitative review of
      published observational epidemiological studies on the association between
      smoking and risk of ED was the main outcome measure. RESULTS: One cohort study
      and nine cross-sectional studies were eligible for inclusion in the meta-analysis
      (50,360 participants and 12,218 cases with ED). No evidence of a curve linear
      association was observed between smoking and risk of ED. The summary odds ratio
      of ED for an increase of 10 cigarettes smoked per day was 1.14 (95% confidence
      interval 1.09 to 1.18), with moderate heterogeneity (P = 0.061, I(2)  = 44.7%).
      For an increment of 10 years of smoking, the combined odds ratios of ED was 1.15
      (95% confidence interval 1.10 to 1.19), without substantial heterogeneity (P =
      0.522, I(2)  = 0.0%). CONCLUSIONS: Evidence from observational studies suggests
      that there is a positive dose-response association between quantity and duration
      of smoking and risk of ED.

PMID- 25052870
TI  - Prevalence of locomotive syndrome in Japan: a nationwide, cross-sectional
      Internet survey.
AB  - BACKGROUND: The authors recently developed a screening tool, the 25-question
      Geriatric Locomotive Function Scale (GLFS-25), for the early detection of
      locomotive syndrome (LS). However, the nationwide prevalence of LS based on the
      GLFS-25 remains unknown. METHODS: A nationwide, cross-sectional Internet survey
      was conducted to estimate sex- and age-specific mean values of the GLFS-25 and
      the total number of individuals with LS in Japan. The distribution of the
      subjects' sex, age, geographical location, and population size was approximated
      by that observed in the national population census conducted in 2010. In total,
      4,500 subjects who completed the GLFS-25 questionnaire on the Internet were
      included in the present study. RESULTS: The age-specific mean values for the
      GLFS25 were 5.8 in the 40s, 6.0 in the 50s, 5.9 in the 60s, and 8.8 in the 70s.
      The mean value for the GLFS-25 was significantly higher in the 70s than in the
      other age groups. The mean value for the GLFS-25 was significantly higher in
      females than in males. The prevalence of LS was 8.4% in the 40s and remained
      stable until the 60s, but increased rapidly in the 70s. The overall mean
      prevalence of LS was 10.2%. The total number of individuals between the 40s and
      70s with LS in Japan was roughly estimated to be 6.5 million. CONCLUSIONS: This
      study determined sex- and age-specific estimates for the GLFS-25 using a
      nationwide, cross-sectional Internet survey. The current results highlight the
      magnitude of the problem associated with LS and encourage further large-scale
      population-based epidemiologic studies to determine the accurate prevalence of LS
      using stratified random sampling.

PMID- 25052871
TI  - Transarterial chemoembolization using drug eluting beads and subsequent
      percutaneous MR-guided radiofrequency ablation in the therapy of intermediate
      sized hepatocellular carcinoma.
AB  - OBJECTIVE: To evaluate safety, efficacy, survival and recurrence-free survival of
      transarterial chemoembolization (TACE) with drug eluting (DC) beads combined with
      MR-guided radiofrequency (RF) ablation for the treatment of hepatocellular
      carcinomas (HCC) larger than 3 cm. MATERIALS AND METHODS: This retrospective
      study was approved by the institutional review board. 20 patients (69.6 years +/-
      SD 8.8) with HCC underwent DC Bead TACE and subsequent MR-guided RF ablation.
      Treatment interval varied between 5 and 15 days. Mean HCC diameter was 39 mm +/-
      SD 7 mm (range 31-50mm). Rates of recurrence-free survival and overall survival
      were estimated using the Kaplan-Meier method. RESULTS: Technical success rate,
      primary and secondary technical effectiveness rate were 100%, 90% and 95%,
      respectively. Local tumour progression developed in one patient. Cumulative
      survival rates at 1, 3 and 5 years were 90% (Confidence Interval [CI]: 67%-97%),
      50% (CI: 29%-70%), 27% (CI: 11%-51%) respectively. Median survival time was 37.4
      months. During follow up (mean: 39.1 months +/- SD 22.4; range 5-84 months),
      tumour progression in untreated liver developed in 14 cases. Cumulative
      recurrence-free survival rates at 1, 3 and 5 years were 48% (CI: 27-69%), 16% (5
      39%), 16% (5-39%) respectively. Median recurrence-free survival time was 10.7
      months. One major complication occurred due to misdiagnosed local recurrence.
      CONCLUSION: In conclusion, we demonstrated that MR-guided RF ablation with
      subsequent DC Bead TACE is safe and effective in local tumour control in patients
      with intermediate sized HCC.

PMID- 25052872
TI  - Volume perfusion CT (VPCT) for the differential diagnosis of patients with
      suspected cerebral vasospasm: qualitative and quantitative analysis of 3D
      parameter maps.
AB  - OBJECT: Cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH) implies
      high risk for secondary ischemia. It requires early diagnosis to start treatment
      on time. We aimed to assess the utility of "whole brain" VPCT for detecting
      localization and characteristics of arterial vasospasm. METHODS: 23 patients
      received a non-enhanced CT, VPCT and CTA of the brain. The distribution of
      ischemic lesions was analyzed on 3D-perfusion-parameter-maps of CBF, CBV, MTT,
      TTS, TTP, and TTD. CT-angiographic axial and coronal maximum-intensity
      projections were reconstructed to determine arterial vasospasm. CT-data was
      compared to DSA, if performed additionally. Volume-of-interest placement was used
      to obtain quantitative mean VPCT values. RESULTS: 82% patients (n=19) had focal
      cerebral hypoperfusion. 100% sensitivity and 100% specificity was found for TTS
      (median 1.9s), MTT (median 5.9s) and TTD (median 7.6s). CBV showed no significant
      differences. In 78% (n=18) focal vessel aberrations could be detected either on
      CTA or DSA or on both. CONCLUSION: VPCT is a non-invasive method with the ability
      to detect focal perfusion deficits almost in the whole brain. While DSA remains
      to be the gold standard for detection of CV, VPCT has the potential to improve
      noninvasive diagnosis and treatment decisions.

PMID- 25052873
TI  - Hepcidin and GDF15 in anemia of multiple myeloma.
AB  - Multiple myeloma (MM) is a malignant disease of plasma cells and is often
      accompanied by anemia which may influence its progression and survival. The
      mechanism of anemia of chronic disease (ACD) in which iron homeostasis is
      impaired underlies that of MM-related anemia. In this study, we analyzed the role
      of hepcidin which is the main mediator of ACD and ACD-related cytokines in
      peripheral blood of MM patients. We showed that HAMP mRNA and growth
      differentiation factors 15 (GDF15) mRNA expressions in peripheral blood
      mononuclear cells (PBMCs) and plasma hepcidin, GDF15, interleukin-6 and
      erythropoietin in MM patients all increased significantly as compared to those in
      controls. In MM patients, the expression of HAMP mRNA showed a positive
      correlation with serum ferritin level, and a negative correlation with hemoglobin
      level. The levels of plasma hepcidin and GDF15 were significantly decreased in MM
      patients who achieved complete remission after six cycles VD (bortezomib +
      dexamethasone) regimen chemotherapy. These data indicated that overexpression of
      HAMP mRNA in PBMCs significantly correlated with increased plasma hepcidin level
      and may be involved in the pathogenesis of MM-related anemia. Furthermore, the
      levels of plasma hepcidin and GDF15 may be valuable in assessing the progress of
      MM. 

PMID- 25052874
TI  - Long-term survey of survival time, histological transformation, and secondary
      malignancies in Japanese patients with advanced-stage follicular lymphoma in the
      rituximab era: Hokkaido Hematology Study Group.
AB  - Following the introduction of rituximab, the long-term overall survival (OS) rate
      of advanced-stage follicular lymphoma (FL) cases was expected to improve after
      the introduction of rituximab: however, there is a lack of large-scale survey
      data in Asia due to the relatively low incidence of FL. We conducted a
      retrospective survey to assess the treatment outcomes in patients with newly
      diagnosed advanced-stage FL in 29 institutions in Hokkaido from January 2001 to
      December 2010. The total number of patients was 443 (men 47.6%, women 52.4%),
      with a median age of 55 years (range 20-80 years). Of the cases examined, 42.2%
      had stage III and 57.8% had stage IV disease. Furthermore, 62.5, 19.7, 9.2, 5.2,
      and 3.4% had performance statuses of 0, 1, 2, 3, and 4, respectively. The 5-year
      OS was 91.2%, and no survival plateau was observed. Seventeen patients
      experienced secondary malignancies (six hematological diseases and 11 solid
      cancers; 5-year probability, 4.2%). Eighteen patients experienced transformation
      (5-year probability, 4.5%). The overall survival at 5 years after therapy for
      transformation was 50%. Before the introduction of rituximab, the 5- to 10-year
      OS of advanced-stage FL patients in Japan was reported to be about 30-60%.
      Although these data are limited, improvement in OS has been observed in Japan
      during the rituximab era.

PMID- 25052875
TI  - Marijuana, expectancies, and post-traumatic stress symptoms: a preliminary
      investigation.
AB  - Previous work suggests that people might turn to marijuana to alleviate the
      symptoms of post-traumatic stress disorder (PTSD) and associated distress.
      Expectancy theories emphasize that the use of drugs correlates with their
      anticipated effects. The current study examined multivariate links among
      marijuana use, PTSD symptoms, and expectancies for marijuana-induced changes in
      those symptoms. Over 650 combat-exposed, male veterans who used marijuana at
      least once per week completed measures of PTSD symptoms, marijuana expectancies,
      and marijuana use in an Internet survey. Participants generally expected
      marijuana to relieve PTSD symptoms, especially those related to intrusions and
      arousal. Symptoms, expectancies for relief of symptoms, and marijuana consumption
      correlated significantly. Regressions revealed significant indirect effects of
      symptoms on use via expectancies, but no significant interactions of expectancies
      and symptoms. Combat-exposed veterans who use marijuana appear to use more as the
      magnitude of PTSD symptoms and their expectations of marijuana-induced relief of
      those symptoms increase. These results emphasize the importance of PTSD
      treatments in an effort to keep potential negative effects of marijuana to a
      minimum. They also underscore the import of expectancies in predicting marijuana
      use.

PMID- 25052876
TI  - The role of alcohol expectancies in drinking behavior among women with alcohol
      use disorder and comorbid posttraumatic stress disorder.
AB  - Understanding how alcohol expectancies relate to alcohol use among individuals
      with concurrent alcohol use disorder (AUD) and posttraumatic stress disorder
      (PTSD) is important to understanding and treating this comorbidity. This study
      examined the role of positive and negative alcohol expectancies and PTSD symptoms
      in drinking behavior in a comorbid female sample. Participants were women (n =
      33; 56% Caucasian) seeking AUD and PTSD treatment in an outpatient community co
      occurring disorders program. Hypotheses related to drinking days and alcohol
      problems outcomes were evaluated using negative binomial hierarchical regression.
      PTSD symptoms were associated with fewer reported days of alcohol-related
      problems. Negative expectancies related to negative changes in social behavior
      associated with drinking days and cognitive and motor impairment associated with
      problems. Both the general positive expectancies score and specific global
      positive change subscale were uniquely associated with drinking and alcohol
      related problems days after controlling for PTSD symptom severity and negative
      expectancies scores. Results suggest that both negative and positive expectancies
      about alcohol's effects are important correlates of drinking behavior among women
      with AUD and PTSD, with positive expectancies playing a potentially more salient
      role on use and consequences than symptom severity and negative expectancies.

PMID- 25052877
TI  - Do incest, depression, parental drinking, serious romantic relationships, and
      living with parents influence patterns of substance use during emerging
      adulthood?
AB  - This study examined how incest, depression, parental drinking, relationship
      status, and living with parents affect patterns of substance use among emerging
      adults, 18 to 25 years old. The study sample included (n = 11,546) individuals
      who participated in Waves I, II, and III of the National Longitudinal Study of
      Adolescent Health (Add Health). The study used separate latent class analysis for
      males and females to determine how patterns of substance use clustered together.
      The study identified the following three classes of substance use: heavy,
      moderate, and normative substance use patterns. Multinomial logistic regression
      indicated that, for females only, incest histories also nearly doubled the risk
      of heavy-use class membership. In addition, experiencing depression, being
      single, and not living with parents serve as risk factors for males and females
      in the heavy-use group. Conversely, being Black, Hispanic, or living with parents
      lowered the likelihood of being in the group with the most substance use
      behaviors (i.e., heavy use). Findings highlight the need for interventions that
      target depression and female survivors of incest among emerging adults.

PMID- 25052878
TI  - Sources of pharmaceutical opioids for non-medical use among young adults.
AB  - The study uses qualitative and quantitative data to describe sources of pain
      pills for illicit use among young adult (18- to 23-year-old) users. Respondent
      driven sampling was used to recruit 383 individuals in the Columbus, Ohio, area.
      The sample was almost 50% Caucasian and about 55% male. Qualitative interview
      participants (n = 45) were selected from the larger sample. Qualitative data
      suggest that pharmaceutical opioid availability was so pervasive that most
      individuals did not have to venture outside of their immediate social networks to
      find people who sold or shared pills. Participants emphasized differences between
      those who are actively involved in obtaining pills and those who play a more
      passive role. Active involvement was described as going out searching for pills
      and paying money to obtain them. In contrast, passive role included obtaining
      pills when somebody offered or shared them free of charge. Multiple logistic
      regression analysis indicates that a more active role in obtaining pharmaceutical
      opioids was related to being White, more frequent use of pharmaceutical opioids,
      extended-release oxycodone use, and using pharmaceutical opioids to get high, as
      opposed to self-treating a health problem. The study results can help inform drug
      use epidemiology, interventions, and policy.

PMID- 25052879
TI  - Correlates of having never been HIV tested among entrants to substance abuse
      treatment clinics: empiric findings from real-world New England settings.
AB  - Routine testing is the cornerstone to identifying HIV, but not all substance
      abuse treatment patients have been tested. This study is a real-world evaluation
      of predictors of having never been HIV tested among patients initiating substance
      abuse treatment. Participants (N = 614) from six New England clinics were asked
      whether they had ever been HIV tested. Eighty-five patients (13.8%) reported
      having never been tested and were compared to those who had undergone testing.
      Clinic, male gender (adjusted odds ratio (AOR) = 1.91, 95% confidence interval
      (CI) = 1.07-3.41), and having fewer employment (AOR = 0.31; 95% CI = 0.11-0.88)
      and medical problems (AOR = 0.40, 95% CI = 0.17-0.99) were independently
      correlated with having never been HIV tested. Thus, there is still considerable
      room for improved testing strategies as a clinically significant minority of
      substance abuse patients have never undergone HIV testing when they initiate
      treatment.

PMID- 25052880
TI  - A qualitative study of methamphetamine users' perspectives on barriers and
      facilitators of drug abstinence.
AB  - To better understand methamphetamine (MA) use patterns and the process of
      recovery, qualitative interviews were conducted with adult MA users (n = 20),
      comparing a sample that received substance abuse treatment with those who had not
      received treatment. Respondents provided detailed information on why and how they
      changed from use to abstinence and factors they considered to be barriers to
      abstinence. Audio recordings and transcripts were reviewed for common themes.
      Participants reported a range of mild/moderate to intensely destructive problems,
      including loss of important relationships and profound changes to who they felt
      they were at their core; e.g., "I didn't realize how dark and mean I was ... I
      was like a different person." Initial abstinence was often facilitated by
      multiple external forces (e.g., drug testing, child custody issues, prison,
      relocation), but sustained abstinence was attributed to shifts in thinking and
      salient realizations about using. The treatment group reported using more and
      different resources to maintain their abstinence than the no-treatment group.
      Findings indicate individualized interventions and multiple, simultaneous
      approaches and resources were essential in reaching stable abstinence.
      Understanding long-term users' experiences with MA use, addiction, and abstinence
      can inform strategies for engaging and sustaining MA users in treatment and
      recovery.

PMID- 25052882
TI  - Problem drinking's associations with social structure and mental health care:
      race/ethnicity differences.
AB  - This research used a nationally representative sample of 12,756 respondents self
      identified as White, Black, Hispanic, or Asian to examine problem drinking in
      relationship to social structure and mental healthcare factors. Associations
      between problem drinking and particular factors varied by racial/ethnic group.
      Results also indicated that Whites' problem-drinking rates were higher than those
      of Hispanics, Blacks, and Asians. Americans sometimes use alcohol to manage
      stress stemming from social disadvantage and inadequate material resources.
      Across racial/ethnic groups, drinking level was associated with the type and
      degree of such disadvantage. Additionally, the presence of a mental health
      problem was associated with problem drinking.

PMID- 25052881
TI  - Feasibility of providing interventions for injection drug users in pharmacy
      settings: a case study among San Francisco pharmacists.
AB  - In addition to syringe exchange programs, pharmacies are important venues where
      injection drug users (IDUs) can access non-prescription syringes and other
      prevention interventions. This study assessed the feasibility of providing a
      range of interventions for IDUs in pharmacy settings. Semi-structured qualitative
      interviews were conducted with 23 participants (policy makers, owner/managers,
      dispensing pharmacists, and pharmacy staff) from independent and chain/retail
      pharmacies in San Francisco, California, USA. The highest level of support was
      for a coupon syringe program and educational materials. Several overarching
      themes illustrate challenges to implementing pharmacy-based preventive
      interventions: time, space, sufficient staff, pharmacist training, legal
      considerations, pharmacist attitudes toward IDUs, and cost and reimbursement
      issues. This study provides concrete examples of the types of preventive services
      that pharmacists support and consider feasible, and illustrates that pharmacists
      welcome the opportunity to broaden their role as critical partners in public
      health matters related to injection drug use.

PMID- 25052883
TI  - Gamma-hydroxybutyrate (GHB): a scoping review of pharmacology, toxicology,
      motives for use, and user groups.
AB  - Gamma hydroxybutyrate (GHB) is a central nervous system depressant with euphoric
      and relaxant effects. Documentation of GHB prevalence and the underreporting of
      abuse remains problematic, given the availability of GHB and its precursors gamma
      butyrolactone (GBL) and 1,4-butanediol (1,4-BD) and the ease of synthesis from
      kits available on the Internet. The continued abuse of and dependence on GHB, and
      associated fatalities, present an on-going public health problem. As the drug GHB
      remains an underresearched topic, a scoping review was chosen as a technique to
      map the available literature into a descriptive summarized account. PRISMA was
      used to assist in data retrieval, with subsequent data charting into three key
      themes (pharmacology and toxicology, outcomes, and user groups). Administered
      orally, GHB is dose-dependent and popular for certain uses (therapeutic, body
      enhancement, sexual assault) and amongst user sub groups (recreational party drug
      users, homosexual men). Despite the low prevalence of use in comparison to other
      club drugs, rising abuse of the drug is associated with dependence, withdrawal,
      acute toxicity, and fatal overdose. Clinical diagnosis and treatment is
      complicated by the co-ingestion of alcohol and other drugs. Limitations of the
      scoping review and potential for further research and harm reduction initiatives
      are discussed.

PMID- 25052884
TI  - The effects of ayahuasca ritual participation on gay and lesbian identity.
AB  - The practice of drinking ayahuasca-a psychoactive brew indigenous to the Amazon
      has been investigated in several studies and shown to have positive long-term
      effects on mental states, and a particularly strong positive effect on
      perceptions of identity. This article discusses if these previous findings can be
      found in the experience of gay people, who are often taught by their culture and
      religion that their lifestyles, values, and sexual orientation are unacceptable.
      The qualitative study examined the interview responses of 17 self-identified gay
      and lesbian participants who had drunk ayahuasca in a ceremonial context within
      the past three years, regarding their self-perceptions and integration of group
      beliefs. Participants drank either in shamanic or Santo Daime ceremonies or, in
      the case of one participant, with an Afro-Brazilian group that used ayahuasca.
      Participants reported affirmation of their sexual orientation, and no
      participants reported negative effects on perception of identity. Additional
      positive effects in other areas of their lives, which they attributed to
      ayahuasca sessions, contributed to the overall positive outcomes that were
      reported by this group as a result of their ritual participation.

PMID- 25052886
TI  - Unclaimed health care benefits: a mixed-method analysis of rural veterans.
AB  - PURPOSE: Rural areas contribute a disproportionate number of US military recruits
      compared to urban areas. However, few studies have examined why many rural
      veterans do not enroll in the Veterans Health Administration (VHA) for health
      care. Our objective was to elicit reasons rural veterans chose not to use VHA.
      METHODS: This mixed-methods study included quantitative survey and qualitative
      interview data. Surveys were mailed to 4,176 households with a registered voter
      in a rural Midwestern county to reach the estimated 1,100 veterans, of whom 600
      were not enrolled in VHA. Surveys were designed to assess demographics and basic
      eligibility requirements for VHA. Themes were derived deductively from survey
      responses and inductively as they emerged through analysis of interview
      transcripts. FINDINGS: A total of 180 veterans completed the survey and 165 were
      eligible based on an approximation of enrollment criteria. Of those, 74 (45%)
      were current VHA users, and 91 (55%) were nonusers of VHA but appeared to be
      eligible. The most common reason selected by these potentially eligible veterans
      for not using VHA was they did not think they were eligible (41%). Interviews
      revealed the issue of distance was superseded by the perception that enrollees
      must be poor and have experienced combat, injury, or disability during service.
      Most reported they had never been told about VHA health care benefits.
      CONCLUSIONS: Results suggest that lack of awareness of VHA health care benefits
      may be the biggest barrier identified by rural veterans. Targeted outreach and
      education efforts related to eligibility for rural veterans are warranted.

PMID- 25052887
TI  - Helicobacter pylori induces cell migration and invasion through casein kinase 2
      in gastric epithelial cells.
AB  - BACKGROUND: Chronic infection with Helicobacter pylori (H. pylori) is causally
      linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial
      CagA into gastric epithelial cells. Induction of high motility and an elongated
      phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a
      critical role in carcinogenesis through signaling pathways related to the
      epithelial mesenchymal transition. This study was aimed to investigate the effect
      of H. pylori infection on the casein kinase 2-mediated migration and invasion in
      gastric epithelial cells. MATERIALS AND METHODS: AGS or MKN28 cells as human
      gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and
      Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of
      infection of 100 : 1 for various times. We measured in vitro kinase assay to
      examine casein kinase 2 activity and performed immunofluorescent staining to
      observe E-cadherin complex. We also examined beta-catenin transactivation through
      promoter assay and MMP7 expression by real-time PCR and ELISA. RESULTS: H. pylori
      upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H.
      pylori-infected cells profoundly suppressed cell invasiveness and motility. We
      confirmed that casein kinase 2 mediates membranous alpha-catenin depletion
      through dissociation of the alpha-/beta-catenin complex in H. pylori-infected
      cells. We also found that H. pylori induces beta-catenin nuclear translocation
      and increases MMP7 expressions mediated through casein kinase 2. CONCLUSIONS: We
      show for the first time that CagA(+) H. pylori upregulates cellular invasiveness
      and motility through casein kinase 2. The demonstration of a mechanistic
      interplay between H. pylori and casein kinase 2 provides important insights into
      the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis.

PMID- 25052888
TI  - Perspectives on transgenic, herbicide-resistant crops in the United States almost
      20 years after introduction.
AB  - Herbicide-resistant crops have had a profound impact on weed management. Most of
      the impact has been by glyphosate-resistant maize, cotton, soybean and canola.
      Significant economic savings, yield increases and more efficacious and simplified
      weed management have resulted in widespread adoption of the technology.
      Initially, glyphosate-resistant crops enabled significantly reduced tillage and
      reduced the environmental impact of weed management. Continuous use of glyphosate
      with glyphosate-resistant crops over broad areas facilitated the evolution of
      glyphosate-resistant weeds, which have resulted in increases in the use of
      tillage and other herbicides with glyphosate, reducing some of the initial
      environmental benefits of glyphosate-resistant crops. Transgenic crops with
      resistance to auxinic herbicides, as well as to herbicides that inhibit
      acetolactate synthase, acetyl-CoA carboxylase and hydroxyphenylpyruvate
      dioxygenase, stacked with glyphosate and/or glufosinate resistance, will become
      available in the next few years. These technologies will provide additional weed
      management options for farmers, but will not have all of the positive effects
      (reduced cost, simplified weed management, lowered environmental impact and
      reduced tillage) that glyphosate-resistant crops had initially. In the more
      distant future, other herbicide-resistant crops (including non-transgenic ones),
      herbicides with new modes of action and technologies that are currently in their
      infancy (e.g. bioherbicides, sprayable herbicidal RNAi and/or robotic weeding)
      may affect the role of transgenic, herbicide-resistant crops in weed management.
      Published 2014. This article is a U.S. Government work and is in the public
      domain in the USA. 

PMID- 25052889
TI  - Expression levels of insulin-like growth factors and receptors in hepatocellular
      carcinoma: a retrospective study.
AB  - BACKGROUND: The insulin-like growth factor (IGF) pathway is implicated in the
      pathogenesis of hepatocellular carcinoma (HCC) and may be important in
      nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine
      expression levels of IGFs and receptors in NAFLD-associated HCC. METHODS: Tissue
      microarrays were constructed from patients who underwent hepatectomy for HCC.
      Immunohistochemistry was performed using antibodies for IGF ligands and
      receptors. Immunostain results were scored by a pathologist blinded to clinical
      data. RESULTS: Among 27 patients with HCC, the most common underlying liver
      diseases included NAFLD, hepatitis C, and alcoholic hepatitis. Expression levels
      of IGFs and receptors were not associated with patients' underlying liver
      disease. In all patients, IGF-2 expression was upregulated in tumor and adjacent
      non-neoplastic liver. Expression of IGF-1 was low in adjacent liver in 6 of 10
      patients with cirrhosis, compared with 2 of 17 patients without cirrhosis (P =
      0.025). Higher IGF-1 expression in liver adjacent to tumor was associated with
      poorer median survival of 22 months, compared with 72 months with equal or lower
      IGF-1 expression in adjacent liver relative to tumor (P = 0.006). CONCLUSIONS:
      Our preliminary results demonstrate significant associations between IGF-1
      expression and liver cirrhosis and survival after resection in patients with HCC,
      independent of their underlying liver disease.

PMID- 25052891
TI  - 2D Cd(II)-lanthanide(III) heterometallic-organic frameworks based on
      metalloligands for tunable luminescence and highly selective, sensitive, and
      recyclable detection of nitrobenzene.
AB  - In this work, five novel 2D isostructural Cd(II)-lanthanide(III) heterometallic
      organic frameworks [CdCl(L)Eu(x)Tb(y)(H2O)(DMA)](NO3).3DMA (IFMC-36-Eu(x)Tb(y): x
      = 1, y = 0, IFMC-36-Eu; x = 0.6, y = 0.4, IFMC-36-Eu(0.6)Tb(0.4); x = 0.5, y =
      0.5, IFMC-36-Eu(0.5)Tb(0.5); x = 0.4, y = 0.6, IFMC-36-Eu(0.4)Tb(0.6); x = 0, y =
      1, IFMC-36-Tb; H3L is 4,4',4"-((2,2',2"-(nitrilotris(methylene))tris(1H
      benzo[d]imidazole-2,1-diyl))tris(methylene))tribenzoic acid; IFMC = Institute of
      Functional Material Chemistry) have been successfully synthesized by taking
      advantage of different molar ratios of lanthanide(III) (Ln(III)) and
      metalloligands under solvothermal conditions. Further luminescent measurements
      indicate that IFMC-36-Eu(x)Tb(y) exhibits characteristic sharp emission bands of
      Eu(III) and Tb(III), and the intensities of red and green can be modulated
      correspondingly by tuning the ratios of Eu(III) and Tb(III). Particularly, the
      solvent-dependent luminescent behavior of IFMC-36-Eu shows a potential
      application in detection of small-molecule pollutant nitrobenzene by significant
      fluorescence quenching. Furthermore, IFMC-36-Eu displays preeminent anti
      interference ability and could be used for sensing in the systems with
      complicated components. This is the first time that a d-f heterometallic-organic
      framework can be investigated as a chemical sensor for selective, sensitive, and
      recyclable detection of nitrobenzene.

PMID- 25052890
TI  - Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised
      trial and economic evaluation.
AB  - BACKGROUND: Folate deficiency is associated with depression. Despite the
      biological plausibility of a causal link, the evidence that adding folate
      enhances antidepressant treatment is weak. OBJECTIVES: (1) Estimate the clinical
      effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant
      medication (ADM). (2) Explore whether baseline folate and homocysteine predict
      response to treatment. (3) Investigate whether response to treatment depends on
      genetic polymorphisms related to folate metabolism. DESIGN: FolATED (Folate
      Augmentation of Treatment - Evaluation for Depression) was a double-blind and
      placebo-controlled, but otherwise pragmatic, randomised trial including cost
      utility analysis. To yield 80% power of detecting standardised difference on the
      Beck Depression Inventory version 2 (BDI-II) of 0.3 between groups (a 'small'
      effect), FolATED trialists sought to analyse 358 participants. To allow for an
      estimated loss of 21% of participants over three time points, we planned to
      randomise 453. SETTINGS: Clinical - Three centres in Wales - North East Wales,
      North West Wales and Swansea. Trial management - North Wales Organisation for
      Randomised Trials in Health in Bangor University. Biochemical analysis -
      University Hospital of Wales, Cardiff. Genetic analysis - University of
      Liverpool. PARTICIPANTS: Four hundred and seventy-five adult patients presenting
      to primary or secondary care with confirmed moderate to severe depression for
      which they were taking or about to start ADM, and able to consent and complete
      assessments, but not (1) folate deficient, vitamin B12 deficient, or taking folic
      acid or anticonvulsants; (2) misusing drugs or alcohol, or suffering from
      psychosis, bipolar disorder, malignancy or other unstable or terminal illness;
      (3) (planning to become) pregnant; or (4) participating in other clinical
      research. INTERVENTIONS: Once a day for 12 weeks experimental participants added
      5 mg of folic acid to their ADM, and control participants added an
      indistinguishable placebo. All participants followed pragmatic management plans
      initiated by a trial psychiatrist and maintained by their general medical
      practitioners. MAIN OUTCOME MEASURES: Assessed at baseline, and 4, 12 and 25
      weeks thereafter, and analysed by 'area under curve' (main); by analysis of
      covariance at each time point (secondary); and by multi-level repeated measures
      (sensitivity analysis): Mental health - BDI-II (primary), Clinical Global
      Impression (CGI), Montgomery-Asberg Depression Rating Scale (MADRS), UKU side
      effects scale, and Mini International Neuropsychiatric Interview (MINI)
      suicidality subscale; General health - UK 12-item Short Form Health Survey (SF
      12), European Quality of Life scale - 5 Dimensions (EQ-5D); Biochemistry - serum
      folate, B12, homocysteine; Adherence - Morisky Questionnaire; Economics -
      resource use. RESULTS: Folic acid did not significantly improve any of these
      measures. For example it gained a mean of just 2.9 quality-adjusted life-days
      [95% confidence interval (CI) from -12.7 to 7.0 days] and saved a mean of just
      L48 (95% CI from -L292 to L389). In contrast it significantly reduced mental
      health scores on the SF-12 by 3.0% (95% CI from -5.2% to -0.8%). CONCLUSIONS: The
      FolATED trial generated no evidence that folic acid was clinically effective or
      cost-effective in augmenting ADM. This negative finding is consistent with
      improving understanding of the one-carbon folate pathway suggesting that
      methylfolate is a better candidate for augmenting ADM. Hence the findings of
      FolATED undermine treatment guidelines that advocate folic acid for treating
      depression, and suggest future trials of methylfolate to augment ADM. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN37558856. 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. 48. See the HTA programme
      website for further project information.

PMID- 25052892
TI  - Compositional studies and Biological activities of Perovskia abrotanoides Kar.
      oils.
AB  - BACKGROUND: Current study has been designed to evaluate the chemical composition
      of essential and fixed oils from stem and leaves of Perovskia abrotanoides and
      antioxidant and antimicrobial activities of these oils. RESULTS: GC-MS analysis
      of essential oil identified 19 compounds with (E)-9-dodecenal being the major
      component in stem and hexadecanoic acid in leaves. In contrast, GC-MS analysis of
      fixed oil showed 40 constituents with alpha-amyrin the major component in stem
      and alpha-copaene in leaves. The antioxidant activity showed the highest value of
      76.7% in essential oil from leaves in comparison with fixed oil from stem (45.9%)
      through inhibition of peroxidation in linoleic acid system. The antimicrobial
      assay tested on different microorganisms (e.g. E. coli, S. aureus, B. cereus,
      Nitrospira, S. epidermis, A. niger, A. flavus and C. albicans) showed the higher
      inhibition zone at essential oil from leaves (15.2 mm on B. cereus) as compared
      to fixed oil from stem (8.34 mm on S. aureus) and leaves (11.2 mm on S. aureus).
      CONCLUSIONS: The present study revealed the fact that essential oil analyzed from
      Perovskia abrotanoides stem and leaves could be a promising source of natural
      products with potential antioxidant and antimicrobial activities, as compared to
      fixed oil.

PMID- 25052893
TI  - Peer assessment of aviation performance: inconsistent for good reasons.
AB  - Research into expertise is relatively common in cognitive science concerning
      expertise existing across many domains. However, much less research has examined
      how experts within the same domain assess the performance of their peer experts.
      We report the results of a modified think-aloud study conducted with 18 pilots (6
      first officers, 6 captains, and 6 flight examiners). Pairs of same-ranked pilots
      were asked to rate the performance of a captain flying in a critical pre-recorded
      simulator scenario. Findings reveal (a) considerable variance within performance
      categories, (b) differences in the process used as evidence in support of a
      performance rating, (c) different numbers and types of facts (cues) identified,
      and (d) differences in how specific performance events affect choice of
      performance category and gravity of performance assessment. Such variance is
      consistent with low inter-rater reliability. Because raters exhibited good,
      albeit imprecise, reasons and facts, a fuzzy mathematical model of performance
      rating was developed. The model provides good agreement with observed variations.

PMID- 25052894
TI  - [Snoring in children. Algorithm for diagnostic approach].
AB  - BACKGROUND: Snoring in children is a prevalent symptom and may be an indicator of
      obstructive sleep apnoea. Despite its importance, there is no national guideline
      on its appropriate management. OBJECTIVE: To provide recommendations for the
      management of snoring in children and adolescents treated in a primary care
      setting. METHODS: A total of 16 national paediatric sleep experts were included
      in a Delphi process and formulated recommendations in the form of a step-wise
      work-up procedure. RESULTS: The following 8 steps were developed: (1)
      Identification of true cases of habitual snoring. (2) Identification of high-risk
      patients who should undergo polysomnography in a sleep laboratory. (3)
      Identification of mild cases that may be treated with anti-inflammatory
      medication. (4) Identification of cases that should be referred to an
      otorhinolaryngologist for potential surgery. (5) Performance of polysomnography
      in cases that remain unclear despite steps 3 and 4 to rule out obstructive sleep
      apnoea. (6) Reconsideration of surgery in cases with moderate to severe
      obstructive sleep apnoea. (7) Identification of severe sleep apnoea cases
      requiring continuous positive airway pressure therapy. (8) Identification of
      cases suitable for orthodontic treatment, craniofacial surgery or speech therapy.
      CONCLUSION: This guideline should help to improve the management of snoring
      children and adolescents in Germany.

PMID- 25052895
TI  - [Medicinal treatment of breathing disorders in adenotonsillar hyperplasia].
AB  - BACKGROUND: Adenotonsillar hyperplasia (ATH) can lead to severe breathing
      disorders, such as impaired nasal breathing, mouth breathing, snoring and
      obstructive sleep apnea. In such cases ATH should be treated mostly by performing
      adenoidectomy and/or adenotonsillectomy. There is increasing evidence that anti
      inflammatory medication (AIM) is effective in treating ATH-related breathing
      disorders. OBJECTIVES: The aim of this study was to provide evidence and
      recommendations for the use of AIM in the treatment of ATH-related breathing
      disorders. METHODS: In this study 12 national pediatric sleep experts were
      included into a Delphi process and formulated indications and recommendations.
      RESULTS: The use of AIM in the treatment of ATH-related breathing disorders is
      sufficiently supported by the results of randomized controlled trials and
      systematic reviews. Nasal beclometason and nasal mometason have been studied for
      the treatment of enlarged adenoids and nasal fluticason and oral montelukast for
      the treatment of obstructive sleep apnea. The use of AIM for first-line treatment
      should be restricted to selected indications, such as a characteristic patient
      age and exclusion of an acute upper respiratory tract infection. Evidence-based
      recommendations are given concerning indications, dosage, treatment duration and
      correct administration of AIM. CONCLUSIONS: Anti-inflammatory medications are
      simple and effective alternatives for the treatment of ATH-related breathing
      disorders. These guidelines are intended to promote the use of AIM by
      pediatricians in ambulatory care settings.

PMID- 25052896
TI  - Food consumption of five deep-sea fishes in the Balearic Basin (western
      Mediterranean Sea): are there daily feeding rhythms in fishes living below 1000
      m?
AB  - Predation and food consumption of five deep-sea fish species living below 1000 m
      depth in the western Mediterranean Sea were analysed to identify the feeding
      patterns and food requirements of a deep-sea fish assemblage. A feeding rhythm
      was observed for Risso's smooth-head Alepocephalus rostratus, Mediterranean
      grenadier Coryphaenoides mediterraeus and Mediterranean codling Lepidion
      lepidion. Differences in the patterns of the prey consumed suggest that feeding
      rhythms at such depths are linked with prey availability. The diets of those
      predators with feeding rhythms are based principally on active-swimmer prey,
      including pelagic prey known to perform vertical migrations. The diets of
      Gunther's grenadier Coryphaenoides guentheri and smallmouth spiny eel
      Polyacanthonotus rissoanus, which did not show any rhythm in their feeding
      patterns, are based mainly on benthic prey. Food consumption estimates were low
      (<1% of body wet mass day(-1) ). Pelagic feeding species showing diel feeding
      rhythms consumed more food than benthic feeding species with no feeding rhythms. 

PMID- 25052897
TI  - Plasma cardiotrophin-1 levels are associated with hypertensive heart disease: a
      meta-analysis.
AB  - Cardiotrophin-1 (CT-1) is a member of the interleukin 6 cytokine superfamily.
      Plasma CT-1 levels have been associated with heart failure and hypertension in
      small independent studies. Whether plasma CT-1 levels are associated with
      progression of hypertensive heart disease is poorly understood. The authors
      carried out a meta-analysis using published studies and electronic databases.
      Relevant data were extracted using standardized algorithms. Additional data were
      obtained directly from investigators when indicated. A total of 18 studies were
      included that reported on association between CT-1 level and hypertension (n=8),
      cardiac hypertrophy (n=9), and heart failure (HF) (n=10). The serum levels of CT
      1 were significantly higher in patients with hypertension (standard mean
      difference [SMD], 0.85; 95% confidence interval [CI], 0.64-1.06 fmol/mL), left
      ventricular hypertrophy (SMD, 0.88; 95% CI 0.60-1.17 fmol/mL), or HF (SMD, 0.66;
      95% CI, 0.51-0.80 fmol/mL) compared with controls. Subgroup analysis revealed CT
      1 levels to be highest in patients with hypertension-induced hypertrophy with HF,
      followed by patients with hypertension-induced left ventricular hypertrophy
      without HF (SMD, 0.52; 95% CI, 0.30-0.75 fmol/mL), patients with hypertension
      without left ventricular hypertrophy (SMD, 0.67; 95% CI, 0.46-0.88 fmol/mL) as
      compared with normotensive patients (SMD, 0.74; 95% CI, 10.45-1.04 fmol/mL).
      Increased plasma CT-1 levels are associated with risk for HF in hypertensive
      patients. CT-1 may serve as a novel biomarker in determining prognosis in
      hypertensive patients.

PMID- 25052898
TI  - [Skin depression and progressive induration of extremities: "groove sign"].

PMID- 25052899
TI  - [Drug-induced liver injury caused by simvastatin associated with antinuclear
      antibodies].

PMID- 25052900
TI  - [Chronic hepatitis C treatment in human infection virus coinfected patients].

PMID- 25052901
TI  - Comment on Xu et al.: Meta-analysis of methylcobalamin alone and in combination
      with lipoic acid in patients with diabetic peripheral neuropathy.

PMID- 25052902
TI  - Comparative effect of irradiation and heating on the microbiological properties
      of licorice (Glycyrrhiza glabra L.) root powders.
AB  - PURPOSE: To determine the effect of gamma irradiation, steaming and heating on
      microbial load and chemical composition of licorice root powder. MATERIALS AND
      METHODS: Powders were exposed to hot air treatment at 60 degrees C for 24 h,
      steaming at 1.1 bar and about 121 degrees C for 15 min, and irradiation at 10 kGy
      using a (60)Co source. Microbial load, moisture, ash, and electrical conductivity
      (EC) values of licorice root powders were evaluated immediately after treatment,
      and after 12 months of storage. RESULTS: Total aerobic plate count (TAPC) of
      licorice roots powder (control sample), including coliform, Escherichia coli, and
      Klebsiella spp. were relatively high. Irradiation reduced the TAPC by 4 logs and
      total coliform to negative (less than 1 log(10) colony forming units (CFU) g(-1))
      Klebsiella spp., E. coli, and Salmonella spp. were not detected (less than 1
      log(10) CFU/g) in irradiated sample. Meanwhile, heating and steaming reduced the
      total count by 1 and 2 logs with slight effect on reducing the total coliforms
      counts. Also, irradiated samples were free of coliforms. No considerable changes
      in the moisture and ash were observed in irradiated powders, but the moisture
      increased due to steaming, and decreased due to dried heating. CONCLUSION: Gamma
      irradiation at 10 kGy was more effective than heating and steaming treatments in
      their microbial decontamination effect on the licorice root powders.

PMID- 25052903
TI  - Cost effectiveness of liraglutide in type II diabetes: a systematic review.
AB  - BACKGROUND: As novel treatments for type II diabetes enter the market, there is a
      need to assess their long-term clinical and economic outcomes against currently
      available treatment alternatives. Objective compilation and evaluation of current
      pharmacoeconomic evidence can assist payers and decision makers in determining
      the appropriate place in therapy of a new medication. OBJECTIVE: Our objective
      was to review the existing pharmacoeconomic literature evaluating the cost
      effectiveness and overall costs of treatment associated with liraglutide in type
      II diabetes. DATA SOURCES: Medical literature indexed in MEDLINE, EMBASE,
      PsycINFO, CINAHL, and EconLit through 1 June 2014 was searched. STUDY SELECTION:
      Full-text, English-language cost-effectiveness, cost-utility, and other cost
      analyses in type II diabetes that compared liraglutide to one or more anti
      diabetic agents were included. Initial screening was based on relevance of titles
      and abstracts followed by examination of the study methods of each remaining
      manuscript. Studies conducting original pharmacoeconomic analyses were chosen for
      inclusion. STUDY APPRAISAL METHODS: Articles meeting the inclusion criteria were
      retrieved, and information on the study design and results was abstracted.
      Abstracted data elements were chosen and assessed based on the authors'
      experience as well as criteria set forth by the International Society for
      Pharmacoeconomics and Outcomes Research (ISPOR) Health Economic Evaluation
      Publication Guidelines Task Force. Additionally, reported incremental cost
      effectiveness ratios (ICERs) and selected sensitivity analysis results were
      converted to $US, year 2012 values, in order to facilitate comparison across
      studies. RESULTS: A total of six cost studies and seven cost-utility studies were
      identified for inclusion. Across cost studies, liraglutide treatment resulted in
      costs ranging from a loss of $US2,730 (liraglutide 1.8 mg vs. sitagliptin;
      pharmacy costs only) over a 1-year time horizon to a savings of $US9,367
      (liraglutide 1.8 mg vs. glimepiride; diabetes-related complication costs only)
      over a 30-year time horizon. Cost-utility analysis results reported base-case
      ICERs ranging from $US15,774 (vs. glimepiride) to $US40,128 (vs. rosiglitazone)
      per quality-adjusted life-year (QALY) ($US, year 2012) for liraglutide 1.2 mg and
      $US8,497 (vs. exenatide) to $US66,031 (vs. rosiglitazone)/QALY ($US, year 2012)
      for liraglutide 1.8 mg. Estimates were most sensitive to variations in time
      horizon and cardiovascular complication rates. Based on frequently cited, country
      specific cost-utility thresholds, liraglutide was determined to have a
      probability of being cost effective of between 58 % (liraglutide 1.8 mg vs.
      sitagliptin) and 93 % (liraglutide 1.2 mg vs. glimepiride). LIMITATIONS:
      Weaknesses of included studies related primarily to study model inputs that
      assumed long-term morbidity and mortality benefits in favor of liraglutide based
      on improvements in clinical biomarkers observed in short-term clinical trials.
      The exclusion of drug acquisition costs in two identified cost studies as well as
      the assumed lifetime duration of treatment with liraglutide in several cost
      utility studies were also identified as weaknesses. The authors' review was
      limited by the possibility of incomplete literature retrieval, unintended
      omission of relevant data elements, and comparison of costs and ICERs generated
      from healthcare systems from differing countries. CONCLUSIONS: The current
      literature presents liraglutide as a cost-effective adjunct treatment for type II
      diabetes that may also be associated with a reduction in diabetes-related
      complication costs; however, ICER values are largely dependent on assumptions
      regarding the benefits of long-term liraglutide treatment and the time horizon of
      the analysis. Real-world use may make liraglutide unattractive from a payer and
      policy-maker perspective.

PMID- 25052904
TI  - Acute and perinatal programming effects of a fat-rich diet on rat muscle
      mitochondrial function and hepatic lipid accumulation.
AB  - OBJECTIVE: Maternal high-fat intake during pregnancy may have long-term
      consequences in the offspring. Since this might relate to the capacity of
      mitochondrial metabolic adaptation and hepatic lipid metabolism, we investigated
      how maternal high-fat intake affected mitochondrial function and hepatic
      steatosis in the offspring. DESIGN: Sprague-Dawley rats were fed a high-fat (20%
      w/w) or a control diet (chow, C) from 10 days before pregnancy and throughout
      lactation. At weaning the litters were split into two groups; one was continued
      on the maternal diet and the other was fed low-fat chow. SAMPLE: Skeletal muscle
      mitochondria and liver lipids. METHODS: Mitochondrial respiration and hepatic
      lipid content were determined during and after weaning, on days 20 and 70
      postpartum. MAIN OUTCOME MEASURES: Mitochondrial function and hepatic lipids.
      RESULTS: At 20 days, maternal high-fat diet caused increased Vo2max with pyruvate
      as substrate (p=0.047), at 70 days, pups born by C-dams, but not those born by
      high-fat-dams, showed increased oxidation of palmitoylcarnitine in the absence of
      ADP (p=0.018). Rates of ADP-stimulated oxygen consumption, maximal respiratory
      capacity and mitochondrial respiratory control ratio with pyruvate, increased
      post weaning (p<0.001), whereas respiratory control ratio with palmitoylcarnitine
      decreased (p=0.013). The increase in respiratory control ratio was most
      pronounced in pups from C-dams (p=0.05). The high-fat-diet caused pronounced
      hepatic steatosis in pups at weaning (p<0.001), without concomitant ceramide
      accumulation, while high-fat-feeding after weaning induced triacylglycerol and
      ceramide accumulation (p<0.01), regardless of maternal diet. CONCLUSION: Intake
      of a fat-rich diet during pregnancy and lactation reduced the age-induced
      increases in un-coupled fat oxidation.

PMID- 25052905
TI  - The influence of parenting style on health related behavior of children: findings
      from the ChiBS study.
AB  - OBJECTIVE: Exploring associations between parenting behavior and children's
      health related behavior including physical activity, sedentary behavior, diet and
      sleep. METHODS: We recruited 288 parents and their children (6-12y old).
      Children's weight and height were measured. Fat percentage was determined by air
      displacement plethysmography. Parents reported socio-demographic data, sleep
      information, physical activity and sedentary behavior of their child and
      completed the Comprehensive General Parenting Questionnaire (CGPQ) and a Food
      Frequency Questionnaire. Children completed the Dutch Eating Behavior
      Questionnaire. Associations between parenting behavior (CGPQ) and children's
      health related behavior were assessed with univariate and multiple regression
      analyses. RESULTS: A small positive correlation was found between sweet food
      consumption frequency and "coercive control" (r = 0.139) and a small negative
      correlation between fruit and vegetables consumption frequency and
      "overprotection" (r = -0.151). Children consumed more frequently soft drinks when
      their parents scored lower on "structure" (r = -0.124) and higher on
      "overprotection" (r = 0.123); for the light soft drinks separately, a small
      positive correlation with "behavioral control" was found (r = 0.172). A small
      negative correlation was found between "emotional eating" and "structure" (r = 
      0.172) as well as "behavioral control" (r = -0.166). "Coercive control" was
      negatively correlated with the child's sleep duration (r = -0.171). After
      correction for confounding factors, the following significant associations were
      found: (1) a small negative association between "structure" and soft drinks
      consumption (beta = -0.17 for all soft drinks and -0.22 for light soft drinks),
      (2) a small positive association between "behavioral control" and light soft
      drinks (beta = 0.34), (3) a small positive association of "nurturance" and
      "coercive control" with sedentary behavior (beta = 0.16 for both parent
      constructs) and (4) a small negative association between the parenting construct
      "coercive control" and sleep duration (beta = -0.23). CONCLUSION: The significant
      but small associations between parenting constructs and the investigated
      variables suggest that different aspects of parenting style play an important
      role in the genesis of the health related behavior of children. Overall, our
      findings suggest that health professionals should encourage parents to apply the
      more positive parenting constructs i.e., more "structure" and "behavioral
      control", and less "coercive control". They could, for instance, supervise and
      manage their child's activities and help their child to achieve certain goals.

PMID- 25052906
TI  - Fluorescence-based endoscopic imaging of Thomsen-Friedenreich antigen to improve
      early detection of colorectal cancer.
AB  - Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated
      carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer
      (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen
      expression is associated with tumor invasion and metastasis. In this study, we
      sought to validate a novel nanobeacon for imaging TF-associated CRC in a
      preclinical animal model. We developed and characterized the nanobeacon for use
      with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat
      model of CRC. Both white light and fluorescence colonoscopy methods were utilized
      to establish the ratio-imaging index for the probe. The nanobeacon exhibited
      specificity for TF-associated cancer. Fluorescence colonoscopy using the probe
      can detect lesions at the stage which is not readily confirmed by conventional
      visualization methods. Further, the probe can report the dynamic change of TF
      expression as tumor regresses during chemotherapy. Data from this study suggests
      that fluorescence colonoscopy can improve early CRC detection. Supplemented by
      the established ratio-imaging index, the probe can be used not only for early
      detection, but also for reporting tumor response during chemotherapy.
      Furthermore, since the data obtained through in vivo imaging confirmed that the
      probe was not absorbed by the colonic mucosa, no registered toxicity is
      associated with this nanobeacon. Taken together, these data demonstrate the
      potential of this novel probe for imaging TF antigen as a biomarker for the early
      detection and prediction of the progression of CRC at the molecular level. 

PMID- 25052907
TI  - Cryopreservation of human dental follicle tissue for use as a resource of
      autologous mesenchymal stem cells.
AB  - The main purpose of this study was to develop a cryopreservation method for human
      dental follicle tissue to maintain autologous stem cells as a resource. A
      modified cryoprotectant, consisting of 0.05 m glucose, 0.05 m sucrose and 1.5 m
      ethylene glycol in phosphate-buffered saline (PBS) was employed, with a slow-ramp
      freezing rate. We observed > 70% of cell survival rate after 3 months of tissue
      storage. Isolated and cultured human dental stem cells (hDSCs) from cryopreserved
      dental follicles expressed mesenchymal stem cell markers at a level similar to
      that of hDSCs from fresh tissue. They also successfully differentiated in vitro
      into the mesenchymal lineage, osteocytes, adipocytes and chondrocytes under
      specific inductions. Using immunohistochemistry, the early transcription factors
      OCT4, NANOG and SOX2 were moderately or weakly detected in the nucleus of both
      fresh and cryopreserved dental follicles. In addition, p63, CCND1, BCL2 and BAX
      protein expression levels were the same in both fresh and cryopreserved tissues.
      However, the positive-cell ratio and intensity of p53 protein was higher in
      cryopreserved tissues than in fresh tissues, indicating direct damage of the
      freeze-thawing process. Real-time PCR analysis of hDSCs at passage 2 from both
      fresh and cryopreserved dental follicles showed similar levels of mRNA for
      apoptosis- and transcription-related genes. Based on these results, a newly
      developed cryoprotectant, along with a slow ramp rate freezing procedure allows
      for long-term dental tissue preservation for later use as an autologous stem cell
      resource in regenerative cell therapy. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25052908
TI  - What science are you singing? A study of the science image in the mainstream
      music of Taiwan.
AB  - Previous research showed that pop music bands in the Western world have sometimes
      included science imagery in their lyrics. Their songs could potentially be
      helpful facilitators for science communication and public engagement purposes.
      However, so far no systematic research has been conducted for investigating
      science in popular music in Eastern cultures. This study explores whether science
      has been regarded as an element in the creation of popular mainstream music, and
      examines the content and quantity of distribution through an analysis of
      mainstream music lyrics, to reflect on the conditions of the absorption of
      science into popular culture. The results indicate that expressions related to
      astronomy and space science feature very prominently. Most of the lyrics are
      connected to emotional states and mood expressions and they are only very rarely
      related to actual issues of science. The implications for science communication
      and further research are discussed in the final section. 

PMID- 25052912
TI  - ZmCPK1, a calcium-independent kinase member of the Zea mays CDPK gene family,
      functions as a negative regulator in cold stress signalling.
AB  - Calcium-dependent protein kinases (CDPKs) have been shown to play important roles
      in plant environmental stress signal transduction. We report on the
      identification of ZmCPK1 as a member of the maize (Zea mays) CDPK gene family
      involved in the regulation of the maize cold stress response. Based upon in
      silico analysis of the Z. mays cv. B73 genome, we identified that the maize CDPK
      gene family consists of 39 members. Two CDPK members were selected whose gene
      expression was either increased (Zmcpk1) or decreased (Zmcpk25) in response to
      cold exposure. Biochemical analysis demonstrated that ZmCPK1 displays calcium
      independent protein kinase activity. The C-terminal calcium-binding domain of
      ZmCPK1 was sufficient to mediate calcium independency of a previously calcium
      dependent enzyme in chimeric ZmCPK25-CPK1 proteins. Furthermore, co-transfection
      of maize mesophyll protoplasts with active full-length ZmCPK1 suppressed the
      expression of a cold-induced marker gene, Zmerf3 (ZmCOI6.21). In accordance,
      heterologous overexpression of ZmCPK1 in Arabidopsis thaliana yielded plants with
      altered acclimation-induced frost tolerance. Our results identify ZmCPK1 as a
      negative regulator of cold stress signalling in maize. 

PMID- 25052913
TI  - Does quantitative EMG differ myotonic dystrophy type 2 and type 1?
AB  - Genetic testing is considered the only reliable diagnostic approach in myotonic
      dystrophy. However it has recently been reported that a considerable number of
      patients with genetically proven types of the disease have unusual phenotypic
      presentation. The aim of our study was to evaluate motor unit reorganization
      reflected by various electrophysiological abnormalities in myotonic dystrophies
      and to compare findings between type 1 (DM 1) and type 2 myotonic dystrophy
      (DM2). Quantitative electromyography (EMG) recordings in 63 patients (33 with DM1
      and 30 with DM2) from the biceps brachii (BB), rectus femoris (RF), first dorsal
      interosseus (FDI), and tibialis anterior (TA) muscles were analyzed. Mean
      amplitude and size index (SI) of motor unit potentials recorded in TA and RF
      muscles, mean potential duration in TA, and mean SI and the number of outliers
      with amplitude above the normal range in BB were significantly increased in DM2
      as compared to DM1. Myotonic discharges were recorded more frequently in DM1 than
      in DM2. EMG findings significantly differ between DM1 and DM2. The presence of
      high amplitude potentials in lower limb muscles in DM2 patients, atypical for
      myogenic muscle lesions, could be explained by muscle fiber hypertrophy observed
      in muscle biopsies. 

PMID- 25052914
TI  - Androgen signalling and steroid receptor crosstalk in endocrine cancers.

PMID- 25052911
TI  - Evaluating insect-microbiomes at the plant-insect interface.
AB  - Plants recognize biotic challengers and respond with the appropriate defense by
      utilizing phytohormone signaling and crosstalk. Despite this, microbes and
      insects have evolved mechanisms that compromise the plant surveillance system and
      specific defenses, thus ensuring successful colonization. In nature, plants do
      not experience insect herbivores and microbes in isolation, but in combination.
      Over time, relationships have developed between insects and microbes, varying on
      a continuum from no-relationship to obligate relationships that are required for
      both organisms to survive. While many reviews have examined plant-insect and
      plant-microbe interactions and the mechanisms of plant defense, few have
      considered the interface where microbes and insects may overlap, and synergies
      may develop. In this review, we critically evaluate the requirements for insect
      associated microbes to develop synergistic relationships with their hosts, and we
      mechanistically discuss how some of these insect-associated microbes can target
      or modify host plant defenses. Finally, by using bioinformatics and the recent
      literature, we review evidence for synergies in insect-microbe relationships at
      the interface of plant-insect defenses. Insect-associated microbes can influence
      host-plant detection and/or signaling through phytohormone synthesis, conserved
      microbial patterns, and effectors, however, microbes associated with insects must
      be maintained in the environment and located in opportunistic positions. 

PMID- 25052910
TI  - Phytohormone regulation of legume-rhizobia interactions.
AB  - The symbiosis between legumes and nitrogen fixing bacteria called rhizobia leads
      to the formation of root nodules. Nodules are highly organized root organs that
      form in response to Nod factors produced by rhizobia, and they provide rhizobia
      with a specialized niche to optimize nutrient exchange and nitrogen fixation.
      Nodule development and invasion by rhizobia is locally controlled by feedback
      between rhizobia and the plant host. In addition, the total number of nodules on
      a root system is controlled by a systemic mechanism termed 'autoregulation of
      nodulation'. Both the local and the systemic control of nodulation are regulated
      by phytohormones. There are two mechanisms by which phytohormone signalling is
      altered during nodulation: through direct synthesis by rhizobia and through
      indirect manipulation of the phytohormone balance in the plant, triggered by
      bacterial Nod factors. Recent genetic and physiological evidence points to a
      crucial role of Nod factor-induced changes in the host phytohormone balance as a
      prerequisite for successful nodule formation. Phytohormones synthesized by
      rhizobia enhance symbiosis effectiveness but do not appear to be necessary for
      nodule formation. This review provides an overview of recent advances in our
      understanding of the roles and interactions of phytohormones and signalling
      peptides in the regulation of nodule infection, initiation, positioning,
      development, and autoregulation. Future challenges remain to unify hormone
      related findings across different legumes and to test whether hormone perception,
      response, or transport differences among different legumes could explain the
      variety of nodules types and the predisposition for nodule formation in this
      plant family. In addition, the molecular studies carried out under controlled
      conditions will need to be extended into the field to test whether and how
      phytohormone contributions by host and rhizobial partners affect the long term
      fitness of the host and the survival and competition of rhizobia in the soil. It
      also will be interesting to explore the interaction of hormonal signalling
      pathways between rhizobia and plant pathogens. 

PMID- 25052915
TI  - The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary
      adenomas.
AB  - Pituitary adenomas are common intracranial neoplasms. Patients with these tumors
      exhibit a wide range of clinically challenging problems, stemming either from
      results of sellar mass effect in pituitary macroadenoma or the diverse effects of
      aberrant hormone production by adenoma cells. While some patients are
      cured/controlled by surgical resection and/or medical therapy, a proportion of
      patients exhibit tumors that are refractory to current modalities. New
      therapeutic approaches are needed for these patients. Activation of the
      AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common
      in human neoplasia, and a number of therapeutic approaches are being employed to
      neutralize activation of this pathway in human cancer. This review examines the
      role of this pathway in pituitary tumors with respect to tumor biology and its
      potential role as a therapeutic target.

PMID- 25052916
TI  - Large gastrointestinal stromal tumor and advanced adenocarcinoma in the rectum
      coexistent with an incidental prostate carcinoma: A case report.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the leading mesenchymal
      neoplasia in the gastrointestinal tract, but GIST arising from the rectum is
      rare. When a secondary neoplasia coexists in the vicinity of a rectal GIST, more
      aggressive treatment strategies may be needed to cure the diseases. PRESENTATION
      OF CASE: We herein describe a 76-year-old man with a large gastrointestinal
      stromal tumor along with an advanced adenocarcinoma in the rectum that coexisted
      with prostate carcinoma. Preoperative examination revealed an advanced
      adenocarcinoma of the upper rectum and a large pelvic mass suggestive of a GIST
      or a neuroendocrine tumor arising from the anterior wall of the lower rectum. To
      eradicate the tumor, total pelvic exenteration with ureterocutaneous fistula was
      carried out after obtaining written informed consent. Immuhistochemical studies
      revealed the concurrence of an advanced rectal cancer (T3, N1, M0) and a
      malignant GIST (c-kit-positive, CD34-positive, vimentin-positive, and CAM5.2
      negative), and an incidental prostatic acinar adenocarcinoma. The patient was
      given adjuvant chemotherapy with imatinib and remains disease-free as of 12
      months after surgery. DISCUSSION: A PubMed search for the case of coexistence of
      GIST with two other malignancies revealed only four cases, making this very rare
      condition. CONCLUSION: Radical surgery with perioperative adjuvant chemotherapy
      using tyrosine kinase inhibitors is the choice for treatment of large GISTs with
      a malignant potential. Our report suggests that aggressive surgical approach
      would be feasible, when a secondary tumor is present near the GIST.

PMID- 25052917
TI  - Early detection of fetal cardiac abnormalities: how effective is it and how
      should we manage these patients?
AB  - Congenital heart defects (CHDs), the most commonly occurring congenital
      malformations, cause significant mortality and morbidity. With the recognition of
      early markers for CHD and the development of better ultrasound resolution,
      interest has turned toward performing a screening anomaly scan, including the
      heart, together with the nuchal scan. It is also possible, with adequate skill
      and training, to competently perform an echocardiogram <16 weeks' gestation. This
      article reviews the detection of major CHD in the first trimester and early
      second trimester including specific markers that help to identify high-risk
      groups for early fetal echocardiography (EFEC). CHD detection during first
      trimester screening is low (2.3-56%) depending on the center's experience and the
      population studied. An increased nuchal translucency, abnormal ductus venosus
      flow, and tricuspid regurgitation in the first trimester are associated with an
      increased CHD risk and can be used together to identify high-risk fetuses for
      EFEC. EFEC requires skilled scanning and the expertise of a fetal
      echocardiographer. In high-risk populations, it is 78.5% sensitive with a 74.5%
      concordance between the EFEC and the mid-gestational echocardiogram. The
      availability of qualified personnel and diagnostic accuracy are prerequisites
      before EFEC can be introduced into management protocols. The limitations of EFEC
      should be recognized, and a later confirmatory echocardiogram is recommended.

PMID- 25052918
TI  - Degradation of phenanthrene by the rhizobacterium Ensifer meliloti.
AB  - The biodegradation of the polycyclic aromatic hydrocarbon phenantherene by the
      rhizobacterial strain Ensifer meliloti P221, isolated from the root zone of plant
      grown in PAH-contaminated soil was studied. Bacterial growth and phenanthrene
      degradation under the influence of root-exuded organic acids were also
      investigated. Analysis of the metabolites produced by the strain by using thin
      layer chromatography, gas chromatography, high-pressure liquid chromatography,
      and mass-spectrometry revealed that phenanthrene is bioconverted via two parallel
      pathways. The first, major pathway is through terminal aromatic ring cleavage
      (presumably at the C3-C4 bond) producing benzocoumarin and 1-hydroxy-2-naphthoic
      acid, whose further degradation with the formation of salicylic acid is difficult
      or is very slow. The second pathway is through the oxidation of the central
      aromatic ring at the C9-C10 bond, producing 9,10-dihydro-9,10
      dihydroxyphenanthrene, 9,10-phenanthrenequinone, and 2,2'-diphenic acid. This is
      the first time that the dioxygenation of phenanthrene at the C9 and C10 atoms,
      proven by identification of characteristic metabolites, has been reported for a
      bacterium of the Ensifer genus.

PMID- 25052919
TI  - Reply: To PMID 24853231.

PMID- 25052920
TI  - The empowerment paradox as a central challenge to patient centered medical home
      implementation in the veteran's health administration.
AB  - In this paper we present results of a mixed methods study conducted to identify
      barriers to team function among staff implementing patient aligned care teams -
      the Department of Veterans Affairs' patient centered medical home (PCMH) model.
      Using a convergent mixed methods design, we administered a standardized survey
      measure (Team and Individual Role Perception Survey) to assess work role
      challenge and engagement; and conducted discussion groups to gather context
      pertaining to role change. We found that the role of primary care providers is
      highly challenging and did not become less difficult over the initial year of
      implementation. Unexpectedly over the course of the first year nurse care
      managers reported a decrease in their perceptions of empowerment and clerical
      associates reported less skill variety. Qualitative data suggest that more
      skilled team members fail to delegate and share tasks within their teams. We
      characterize this interprofessional knowledge factor as an empowerment paradox
      where team members find it difficult to share tasks in ways that are counter to
      traditionally structured hierarchical roles. Health care systems seeking to
      implement PCMH should dedicate resources to facilitating within-team role
      knowledge and negotiation.

PMID- 25052921
TI  - p21-activated kinase 7 is an oncogene in human osteosarcoma.
AB  - p21-activated kinase 7 (PAK7), also named as PAK5, is a member of Rac/Cdc42
      associated Ser/Thr protein kinases. It is overexpressed in some types of cancer
      such as colorectal and pancreatic cancers. However, the expression status and
      biological function of PAK7 in osteosarcoma are still ambiguous. To evaluate the
      expression levels of PAK7 in osteosarcoma tissues and cell lines,
      immunohistochemistry was used. To investigate the role of PAK7 in cell
      proliferation, apoptosis and tumorigenicity in vitro and vivo, a recombinant
      lentivirus expressing PAK7 short hairpin RNA (Lv-shPAK7) was developed and
      transfected into Saos-2 cells. The silencing effect of PAK7 was confirmed by
      quantitative real-time PCR (qRT-PCR) and Western blot technique. PAK7 was
      overexpressed in osteosarcoma tissue and cell line. By knocking-down of PAK7, the
      proliferation and colony formation of Saos-2 cells were inhibited and apoptosis
      enhanced significantly. The in vivo tumorigenic ability in xenograft model of
      Saos-2 cells was also notably inhibited when PAK7 was knocked down. Our results
      imply that PAK7 promotes cell proliferation and tumorigenesis and may be an
      attractive candidate for the therapeutic target of osteosarcoma.

PMID- 25052922
TI  - Effectiveness of exchange nailing and augmentation plating for femoral shaft
      nonunion after nailing.
AB  - PURPOSE: We assessed indications and outcomes of exchange nailing and
      augmentation plating for femoral shaft nonunion following femoral nail failure.
      METHODS: We retrospectively reviewed the records of 21 consecutive patients with
      femoral shaft nonunion treated with femoral nailing from August 2008 to June
      2013. Nonunion cases with infection were excluded from this study. The study
      population consisted of nine men and 12 women, with an average age of 40 (range
      21-61) years. All patients received internal fixation using exchange nailing and
      an augment plate coupled with decortication and bone graft. RESULTS: All patients
      in our study obtained osseous union with a mean time of six (range four to12)
      months. Mean operation time was three hours (range two to five hours), and mean
      blood loss was 800 ml (range 500-950 ml). There were no postoperative
      complications. At the last follow-up, all patients could flex their knees > 110
      degrees . CONCLUSIONS: Exchange nailing and augment plating coupled with
      decortication and bone graft is an effective treatment option for femoral shaft
      nonunion and has more indications and higher union rate than the popular exchange
      nailing treatment.

PMID- 25052923
TI  - Permanent neonatal diabetes mellitus in China.
AB  - BACKGROUND: Permanent neonatal diabetes mellitus (PNDM) is a rare disease, which
      is defined as the onset of diabetes before the age of 6 months with persistence
      through life. Infants with KCNJ11 or ABCC8 genetic mutations may respond to oral
      sulfonylurea therapy. Currently, there are limited studies about the genetic
      analysis and long-term follow-up of PNDM. CASE PRESENTATION: We report four cases
      of PNDM. None of the infants or their parents had INS, KCNJ11, or ABCC8 genetic
      mutations. One infant underwent continuous subcutaneous insulin infusion (CSII)
      and the other infants underwent multiple injections of insulin (MII). In these
      infants, PNDM persisted from 35 months to 60 months of follow-up. Three infants
      maintained fairly stable blood sugar levels, and one infant had poor sugar
      control. CONCLUSIONS: We suggest that all of the infants with PNDM should undergo
      genetic evaluation. For infants without KCNJ11 and ABCC8 genetic mutations, oral
      sulfonylurea should not be considered as treatment. CSII is a useful method for
      overcoming the difficulties of diabetes, and it may also improve the quality of
      life of both infants and their parents.

PMID- 25052929
TI  - Aggregate prevention.

PMID- 25052930
TI  - Screened DNA packs faster.

PMID- 25052931
TI  - Complementary observables.

PMID- 25052932
TI  - Stains of authenticity.

PMID- 25052933
TI  - Getting more from photons.

PMID- 25052936
TI  - Using synchronous distance-education technology to deliver a weight management
      intervention.
AB  - OBJECTIVE: To compare the effectiveness of online delivery of a weight management
      program using synchronous (real-time), distance-education technology to in-person
      delivery. METHODS: Synchronous, distance-education technology was used to conduct
      weekly sessions for participants with a live instructor. Program effectiveness
      was indicated by changes in weight, body mass index (BMI), waist circumference,
      and confidence in ability to eat healthy and be physically active. RESULTS:
      Online class participants (n = 398) had significantly greater reductions in BMI,
      weight, and waist circumference than in-person class participants (n = 1,313).
      Physical activity confidence increased more for in-person than online class
      participants. There was no difference for healthy eating confidence. CONCLUSIONS
      AND IMPLICATIONS: This project demonstrates the feasibility of using synchronous
      distance-education technology to deliver a weight management program. Synchronous
      online delivery could be employed with no loss to improvements in BMI, weight,
      and waist circumference.

PMID- 25052937
TI  - Barriers and facilitators for teachers' implementation of the curricular
      component of the boost intervention targeting adolescents' fruit and vegetable
      intake.
AB  - OBJECTIVE: To examine barriers and facilitators to teachers' implementation of
      the curricular component of the school-based, multicomponent Boost intervention
      to promote fruit and vegetable intake among 13-year-olds guided by concepts of
      Diffusion of Innovations Theory and findings of previous implementation studies.
      DESIGN: Five focus group and 2 individual interviews. SETTING: Denmark.
      PARTICIPANTS: Twenty-two seventh-grade teachers from 7 of 20 intervention
      schools. Four schools (15 teachers) with a high implementation level and 3 (7
      teachers) with a low implementation level were selected to obtain maximum
      variation in teachers' view. PHENOMENON OF INTEREST: Teacher perceptions of
      implementation of a curricular component. ANALYSIS: Situational Analysis
      including an introductory phase of systematic coding. RESULTS: Teachers'
      commitment to the Boost curriculum was hindered by intervention duration and
      extra workload and motivated by a pre-intervention workshop and the thoroughness
      of the project. Detailed implementation manuals were helpful for some teachers
      but a barrier to others because they limited opportunities for adaptation.
      CONCLUSIONS AND IMPLICATIONS: Implementation of curricular activities in school
      based interventions may be supported by a predefined teaching schedule, detailed
      teacher manuals, clear learning objectives, and a pre-intervention workshop to
      enhance motivation. Situational Analysis may contribute to future implementation
      studies by highlighting the importance of contextual factors.

PMID- 25052938
TI  - The pharmacologic treatment of short bowel syndrome: new tricks and novel agents.
AB  - Short bowel syndrome (SBS) is a manifestation of massive resection of the
      intestines resulting in severe fluid, electrolyte, and vitamin/mineral
      deficiencies. Diet and parenteral nutrition play a large role in the management
      of SBS; however, pharmacologic options are becoming more readily available. These
      pharmacologic agents focus on reducing secretions and stimulating intestinal
      adaptation. The choice of medication is highly dependent on the patient's
      symptoms, remaining anatomy, and risk versus benefit profile for each agent. This
      article focuses on common and novel pharmacologic medications used in SBS,
      including expert advice on their indications and use. 

PMID- 25052940
TI  - Special issue on anaesthesia and cancer.

PMID- 25052939
TI  - Protein charge ladders reveal that the net charge of ALS-linked superoxide
      dismutase can be different in sign and magnitude from predicted values.
AB  - This article utilized "protein charge ladders"-chemical derivatives of proteins
      with similar structure, but systematically altered net charge-to quantify how
      missense mutations that cause amyotrophic lateral sclerosis (ALS) affect the net
      negative charge (Z) of superoxide dismutase-1 (SOD1) as a function of subcellular
      pH and Zn(2+) stoichiometry. Capillary electrophoresis revealed that the net
      charge of ALS-variant SOD1 can be different in sign and in magnitude-by up to 7.4
      units per dimer at lysosomal pH-than values predicted from standard pKa values of
      amino acids and formal oxidation states of metal ions. At pH 7.4, the G85R, D90A,
      and G93R substitutions diminished the net negative charge of dimeric SOD1 by up
      to +2.29 units more than predicted; E100K lowered net charge by less than
      predicted. The binding of a single Zn(2+) to mutant SOD1 lowered its net charge
      by an additional +2.33 +/- 0.01 to +3.18 +/- 0.02 units, however, each protein
      regulated net charge when binding a second, third, or fourth Zn(2+) (DeltaZ <
      0.44 +/- 0.07 per additional Zn(2+) ). Both metalated and apo-SOD1 regulated net
      charge across subcellular pH, without inverting from negative to positive at the
      theoretical pI. Differential scanning calorimetry, hydrogen-deuterium exchange,
      and inductively coupled plasma mass spectrometry confirmed that the structure,
      stability, and metal content of mutant proteins were not significantly affected
      by lysine acetylation. Measured values of net charge should be used when
      correlating the biophysical properties of a specific ALS-variant SOD1 protein
      with its observed aggregation propensity or clinical phenotype.

PMID- 25052947
TI  - Rhinorrhoea in the elderly.
AB  - The ageing population has various medical problems, ranging from relatively minor
      to truly severe. The ageing process includes physiological changes that can also
      aggravate sinonasal problems such as rhinorrhoea. As one of the most troublesome
      condition of this population, the causes of rhinorrhea can be classified as "age
      related, medication induced, secondary to rhinitis and other causes (tumour,
      cerebrospinal fluid (CSF) leakage, etc.)". The underlying aetiology should be
      meticulously investigated. Although common conditions such as "allergic or
      infectious rhinitis" are relatively easy to diagnose and threat, more serious
      causes such as "primary spontaneous CSF rhinorrhea" are hard to manage. The
      treatment options should be individualised to the patient according to his or her
      metabolic, cardiac and central nervous system status. Rapid and accurate
      diagnosis and treatment of the pathology would not only increase the quality of
      life but also decrease morbidity and mortality of this population. As a
      conclusion, rhinorrhoea in the elderly is an important condition that should not
      be overlooked. 

PMID- 25052948
TI  - Self-harm in people with epilepsy: a retrospective cohort study.
AB  - OBJECTIVES: Little is known about self-harm in people with epilepsy, despite
      suicide being recognized as a leading cause of mortality in this population. This
      study aimed to investigate the characteristics of self-harm in people with
      epilepsy, and associated demographic and psychosocial factors. METHODS: Patients
      presenting to hospital following self-harm between 1994 and 2008 were identified
      from the Oxford Monitoring System for Self-Harm. Epilepsy diagnosis was confirmed
      through review of medical records. Demographic features, patient, and self-harm
      characteristics of 132 people with epilepsy and 9,778 self-harm patients without
      epilepsy were compared using a regression model, adjusting for age, sex, and
      repetition. Patients presenting between 1998 and 2008 were followed up for all
      cause mortality to the end of 2011. RESULTS: The rate of self-harm per individual
      with epilepsy was 2.04 (95% confidence interval [CI] 1.85-2.25) times that of the
      comparison group, and time between first and second self-harm events was shorter
      (hazard ratio 1.86; 1.46-2.38). People with epilepsy were significantly more
      likely to use antiepileptic medication in overdose, although overall methods of
      self-harm were similar in the two groups. No significant differences in suicide
      intent scores or the proportion of patients who died by suicide were found.
      Previous outpatient psychiatric treatment, longer duration of unemployment,
      experience of violence, and housing problems were associated with self-harm in
      people with epilepsy. SIGNIFICANCE: People with epilepsy who self-harm do so more
      frequently than other self-harm patients. Clinicians should be aware of this and
      pay attention to contributory factors as these may enhance risk in this
      population. A PowerPoint slide summarizing this article is available for download
      in the Supporting Information section here.

PMID- 25052949
TI  - Simultaneous (1)H and (13)C NMR enantiodifferentiation from highly-resolved pure
      shift HSQC spectra.
AB  - NMR enantiodifferentiation studies are greatly improved by the simultaneous
      determination of (1)H and (13)C chemical shift differences through the analysis
      of highly resolved cross-peaks in spectral aliased pure shift (SAPS) HSQC
      spectra. 

PMID- 25052950
TI  - Increased binding of 5-HT1A receptors in a dissociative amnesic patient after the
      recovery process.
AB  - Dissociative amnesia is characterized by an inability to retrieve information
      already saved in memories. 5-HT has some role in neural regulatory control and
      may be related to the recovery from dissociative amnesia. To examine the role of
      5-HT1A receptors in the recovery from dissociative amnesia, we performed two
      positron emission tomography (PET) scans on a 30-year-old patient of dissociative
      amnesia using [(11)C]WAY-100635, the first at amnesic state, and the second at
      the time he had recovered. Exploratory voxel-based analysis (VBA) was performed
      using SPM software. 5-HT1A BPND images were compared between the patient at
      amnesic and recovery states and healthy subjects (14 males, mean age 29.8 +/-
      6.45) with Jack-knife analysis. 5-HT1A receptor bindings of the patient at the
      recovery state were significantly higher than those of healthy subjects in the
      right superior and middle frontal cortex, left inferior frontal and orbitofrontal
      cortex and bilateral inferior temporal cortex. The increase in BPND values of
      recovery state was beyond 10% of those of amnesia state in these regions except
      in the right superior frontal cortex. We considered that neural regulatory
      control by the increase of 5-HT1A receptors in cortical regions played a role in
      the recovery from dissociative amnesia.

PMID- 25052951
TI  - Response to "toward personalized sexual medicine: where is the evidence?".

PMID- 25052952
TI  - Directing assembly of DNA-coated colloids with magnetic fields to generate rigid,
      semiflexible, and flexible chains.
AB  - We report the formation of colloidal macromolecules consisting of chains of
      micron-sized paramagnetic particles assembled using a magnetic field and linked
      with DNA. The interparticle spacing and chain flexibility were controlled by
      varying the magnetic field strength and the linker spring constant. Variations in
      the DNA lengths allowed for the generation of chains with an improved range of
      flexibility as compared to previous studies. These chains adopted the rigid-rod,
      semiflexible, and flexible conformations that are characteristic of linear
      polymer systems. These assembly techniques were investigated to determine the
      effects of the nanoscale DNA linker properties on the properties of the
      microscale colloidal chains. With stiff DNA linkers (564 base pairs) the chains
      were only stable at moderate to high field strengths and produced rigid chains.
      For flexible DNA linkers (8000 base pairs), high magnetic field strengths caused
      the linkers to be excluded from the gap between the particles, leading to a
      transition from very flexible chains at low field strengths to semiflexible
      chains at high field strengths. In the intermediate range of linker sizes, the
      chains exhibited predictable behavior, demonstrating increased flexibility with
      longer DNA linker length or smaller linking field strengths. This study provides
      insight into the process of directed assembly using magnetic fields and DNA by
      precisely tuning the components to generate colloidal analogues of linear
      macromolecular chains. 

PMID- 25052954
TI  - General unknown screening for pesticides in whole blood and Korean gastric
      contents by liquid chromatography-tandem mass spectrometry.
AB  - A method of simultaneously screening 215 types of pesticides has been established
      by liquid chromatography with tandem mass spectrometry, quadrupole/time of flight
      mass spectrometry and triple quadrupole mass spectrometry. Samples of blood and
      gastric contents were prepared through the modified Quick, Easy, Cheap,
      Effective, Rugged and Safe (QuEChERS) method. A modified QuEChERS that uses
      dispersive solid phase extraction for a small amount of sample, mini-QuEChERS,
      was applied to blood and gastric contents for quick and convenient preparation of
      the sample and to reduce matrix effect. This method of simultaneous
      identification needs the upmost reliability because these results are employed by
      forensic toxicology and may lead to issues with the law. In this study, we
      incorporated the following two concepts to demonstrate its reliability: One
      concept is that two tandem mass spectrometers are applied for the confirmation
      and then a precise compound identification is conducted synchronously at the same
      retention time. The other concept for reliability adopts the approved criterion
      as identification points, defined by EU. Validation of the method was performed
      to assess selectivity, linearity, limit of quantification (LOQ), and recovery by
      standard addition procedure. The result of linearity was almost satisfactory, and
      the LOQ of pesticides detected in whole blood and Korean characteristic gastric
      contents was between 2.5-50 ng/mL. About 90 % of the pesticides had 80-120 %
      recovery in whole blood, and about 78 % of the pesticides had 80-120 % recovery
      in Korean gastric contents. 

PMID- 25052953
TI  - Distribution and diversity of rhizobia associated with wild soybean (Glycine soja
      Sieb. & Zucc.) in Northwest China.
AB  - A total of 155 nodule isolates that originated from seven sites in Northwest
      China were characterized by PCR-RFLP of the 16S rRNA gene and sequence analysis
      of multiple core genes (16S rRNA, recA, atpD, and glnII) in order to investigate
      the diversity and biogeography of Glycine soja-nodulating rhizobia. Among the
      isolates, 80 were Ensifer fredii, 19 were Ensifer morelense, 49 were Rhizobium
      radiobacter, and 7 were putative novel Rhizobium species. The phylogenies of E.
      fredii and E. morelense isolates in a concatenate tree (assembly of all
      housekeeping genes) were generally consistent with those in individual gene
      trees. However, incongruence was found in the phylogenies of the different genes
      of Rhizobium isolates, indicating that lateral transfer or recombination possibly
      occurred in these gene loci. Despite their species identity, all the isolates in
      this study formed a single lineage related to E. fredii in nodAand nifH gene
      phylogenies, which also indicated that the symbiotic genes were laterally
      transferred between different species. Biogeographic patterns were found at the
      species and strain genomic type levels, as revealed by BOXA1R fingerprinting,
      demonstrating that the evolution of rhizobial populations in different geographic
      locations was related to soil types, altitude and spatial effects. This study is
      the first to report that E. morelense, R. radiobacter, and Rhizobium sp. are
      microsymbionts of G. soja, as well as showing that the diversity of G. soja
      rhizobia is enhanced and new rhizobia have evolved in Northwest China.

PMID- 25052955
TI  - Selective induction of hepatic cytochrome P450 2B activity by leelamine in vivo,
      as a potent novel inducer.
AB  - Cytochrome P450 (CYP) is an important enzyme that can act on xenobiotic
      substances such as toxic chemicals or drugs. Phenobarbital (PB) has been widely
      used to induce CYP2B activity to investigate the drug-drug interaction of CYP2B
      substrate drugs. Leelamine is a diterpene compound, and is the current focus of
      efforts to develop a treatment for diabetes. In this study, we identified the
      selective and potent inductive effect of leelamine on CYP2B at doses of 5, 10, or
      20 mg/kg in male ICR mice for 1 or 3 days. In liver, the activity of CYP2B
      significantly increased 3.6-fold after treatment with leelamine, compared to
      vehicle-treated group. Activities of benzyloxyresorufin O-dealkylase and
      pentoxyresorufin O-dealkylase significantly increased 6.3- and 5.3-fold,
      respectively, with a single treatment of 20 mg/kg leelamine for 1 day.
      Furthermore, immunoblot analysis showed that significantly and dose-dependently
      increased CYP2B10 protein levels in liver. However, PCR results showed that there
      were no significant changes in the CAR and CYP2B mRNA levels after leelamine
      treatment. Accordingly, we suggest that leelamine is a novel substitute of PB for
      the selective induction of CYP2B activity in vivo. 

PMID- 25052956
TI  - Determination of the R-enantiomer of valsartan in pharmaceutical formulation by
      capillary electrophoresis.
AB  - Capillary zone electrophoresis was successfully applied to the enantiomeric
      purity determination of valsartan using acetyl-beta-cyclodextrin (A-beta-CD) as a
      chiral selector. Separations were carried out in a 50 um, 64/56 cm fused-silica
      capillary. The optimized conditions included 25 mM phosphate buffer, pH 8.0,
      containing 10 mM A-beta-CD as background electrolyte, an applied voltage of +30
      kV and a temperature of 30  degrees C. Ibuprofen was used as an internal
      standard. The assay was validated for the R-enantiomer of valsartan in the range
      of 0.05-3.0%. The limit of detection was 0.01%, the limit of quantitation was
      0.05%, relative to a concentration of valsartan of 1 mg/ml. Intra-day precision
      varied between 2.57 and 5.60%. Relative standard deviations of inter-day
      precision ranged between 4.46 and 6.76% for peak area ratio. The percentage
      recovery of the R-enantiomer of valsartan ranged between 97.0 and 99.6% in
      valsartan product. The assay was applied to the determination of the chiral
      purity of valsartan tablets and R-enantiomer of valsartan was found as an
      impurity.

PMID- 25052957
TI  - Characterization of the physicochemical properties of KRK-701P.
AB  - KRK-701P is a broad-spectrum antibiotic with methicillin-resistant antibacterial
      activity. The objective of this preformulation study was to determine the
      physicochemical properties of KRK-701P. The n-octanol-to-water partition
      coefficients of KRK-701P were 0.448 at pH 4 and 2.546 at pH 8. One crystal form
      and one amorphous form of KRK-701P were isolated by recrystallization and
      characterized by differential scanning calorimetry, powder X-ray diffractometry
      and thermogravimetric analysis. After storage for 1 month at 0% RH (silica gel,
      20  degrees C), 52% RH (saturated solution of Na2Cr2O7.2H2O/20  degrees C) and
      95% RH (saturated solution of Na2HPO4/20  degrees C), the two forms were not
      transformed.

PMID- 25052958
TI  - Long chain microRNA conjugates in calcium phosphate nanoparticles for efficient
      formulation and delivery.
AB  - A long chain microRNA-34a conjugate (lc-miRNA) was prepared by chemical
      crosslinking in order to improve entrapment efficiency into calcium phosphate
      nanoparticles (CaPs) and intracellular delivery. Thiol-modified miRNA at both
      terminal ends was chemically conjugated using crosslinkers to form lc-miRNA which
      was encapsulated within CaPs by a conventional co-precipitation method.
      Encapsulation efficiencies, physicochemical properties, and in vitro
      intracellular delivery efficiencies of the prepared linear polyethyleneimine
      (LPEI)-coated CaPs (LPEI-CaP) containing common miRNA and lc-miRNA were
      comparatively evaluated. The prepared lc-miRNA exhibited noticeably enhanced
      encapsulation efficiency during the CaP formulation process when compared to
      common miRNA. LPEI-CaP/lc-miRNAs consisted of nano-sized particles with great
      homogeneity and were observed to be successfully delivered into PC-3 cells.
      Fabricated LPEI-CaPs with duplex form of lc-miRNA (lc-miRNA-d) suppressed cancer
      cell proliferation as well as migration much more efficiently than those with
      duplex form of miRNA (miRNA-d). In addition, LPEI-CaP/lc-miRNA-d conferred
      negligible cytotoxicity on PC-3 cells. Chemical crosslinking of therapeutic
      miRNAs via a reducible linkage may allow more efficient encapsulation within CaPs
      as well as homogeneous particle formulation due to a higher spatial charge
      density than common miRNAs. The well-formulated LPEI-CaPs with lc-miRNA-d have
      the potential to provide superior miRNA transfection efficiency and inhibition of
      cancer proliferation. 

PMID- 25052959
TI  - Metabolism-mediated drug interaction potential of HS-23, a new herbal drug for
      the treatment of sepsis in human hepatocytes and liver microsomes.
AB  - HS-23, an extract of the dried flower buds of Lonicera japonica, is a new
      botanical drug currently being evaluated in a phase I clinical study in Korea for
      the treatment of sepsis. The in vitro induction and inhibition potentials of HS
      23 on the drug-metabolizing enzymes using human hepatocytes and liver microsomes
      were assessed to evaluate herb-drug interaction according to botanical drug
      guideline and drug interaction guidance of FDA. HS-23 slightly inhibited CYP2A6,
      CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activities in human liver microsomes
      with IC50 values of 80.6, 160.7, 169.5, 85.4, and 76.6 MUg/mL, respectively. HS
      23 showed negligible inhibition of CYP1A2, CYP2C8, CYP2D6, UGT1A1, UGT1A4,
      UGT1A9, and UGT2B7 activities in human liver microsomes. Based on these results,
      HS-23 may not inhibit the metabolism of CYP2A6, CYP2B6, CYP2C9, CYP2C19, and
      CYP3A4-catalyzed drugs in humans. HS-23 did not affect the mRNA expression of
      CYP1A2, CYP2B6, and CYP3A4 after 48 h treatment at three concentrations (0.5, 5,
      and 50 MUg/mL) in three independent human hepatocytes, indicating that HS-23 has
      no effect on herb-drug interactions that up- or down-regulate CYP1A2, CYP2B6, and
      CYP3A4. These results indicate that the administration of HS-23 in human may not
      cause clinically relevant inhibition and induction of these cytochrome P450 (CYP)
      and UDP-glucuronosyltransferase (UGT) enzymes and HS-23 may be promising
      therapeutic agent for treatment of sepsis.

PMID- 25052960
TI  - Comparison of the safety and efficacy of biodegradable polymer biolimus-eluting
      stents and durable polymer everolimus-eluting stents: propensity score-matched
      analysis.
AB  - OBJECTIVES: We investigated and compared the clinical outcomes between
      biodegradable polymer biolimus-eluting stents (BES) and durable polymer
      everolimus-eluting stents (EES) in a single-center prospective registry.
      BACKGROUND: There is limited data regarding the safety and efficacy of the
      biodegradable BES compared to second-generation drug-eluting stents. METHODS:
      From January 2010 to April 2012, a total of 1,279 patients were treated with BES
      (n = 647) or EES (n = 632) in a single center. We included 1,231 patients (BES =
      625, EES = 606) after excluding 48 patients (BES = 22, EES = 26) with acute
      myocardial infarction accompanied by cardiogenic shock. The 1-year incidences of
      target lesion failure (TLF), patient-oriented composite outcomes (POCO), and
      stent thrombosis (ST) after the index procedure were compared in propensity score
      matched analyses. RESULTS: Propensity score matching yielded 406 well-balanced
      pairs (EES = 406, BES-B = 406). In the propensity-matched population, the 1-year
      incidence of TLF (BES = 3.0% vs. EES = 2.5%, P = 0.666) and POCO (BES = 5.4% vs.
      EES = 6.4%, P = 0.552) were similar between the 2 groups. In addition, the
      incidence of definite or probable ST was also similar (BES = 0.74% vs. EES =
      0.74%, P = 1.000). In subgroup analysis, the number of patients who reached the
      primary end-point did not differ significantly between the 2 groups. CONCLUSION:
      In a single-center registry with unrestricted use of EES and BES-B, these stents
      showed comparable efficacy and safety in terms of TLF, POCO, and ST at 1-year
      follow-up.

PMID- 25052961
TI  - Differences in gastric mucosal microbiota profiling in patients with chronic
      gastritis, intestinal metaplasia, and gastric cancer using pyrosequencing
      methods.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) infection plays an important role in
      the early stage of cancer development. However, various bacteria that promote the
      synthesis of reactive oxygen and nitrogen species may be involved in the later
      stages. We aimed to determine the microbial composition of gastric mucosa from
      the patients with chronic gastritis, intestinal metaplasia, and gastric cancer
      using 454 GS FLX Titanium. METHODS: Gastric mucosal biopsy samples were collected
      from 31 patients during endoscopy. After the extraction of genomic DNA, variable
      region V5 of the 16S rRNA gene was amplified. PCR products were sequenced using
      454 high-throughput sequencer. The composition, diversity, and richness of
      microbial communities were compared between three groups. RESULTS: The
      composition of H. pylori-containing Epsilonproteobacteria class appeared to be
      the most prevalent, but the relative increase in the Bacilli class in the gastric
      cancer group was noticed, resulting in a significant difference compared with the
      chronic gastritis group. By analyzing the Helicobacter-dominant group at a family
      level, the relative abundance of Helicobacteraceae family was significantly lower
      in the gastric cancer group compared with chronic gastritis and intestinal
      metaplasia groups, while the relative abundance of Streptococcaceae family
      significantly increased. In a UPGMA clustering of Helicobacter-dominant group
      based on UniFrac distance, the chronic gastritis group and gastric cancer group
      were clearly separated, while the intestinal metaplasia group was distributed in
      between the two groups. The evenness and diversity of gastric microbiota in the
      gastric cancer group was increased compared with other groups. CONCLUSIONS: In
      Helicobacter predominant patients, the microbial compositions of gastric mucosa
      from gastric cancer patients are significantly different to chronic gastritis and
      intestinal metaplasia patients. These alterations of gastric microbial
      composition may play an important, as-yet-undetermined role in gastric
      carcinogenesis of Helicobacter predominant patients.

PMID- 25052962
TI  - Green synthesis of highly fluorescent Au(I)@Ag2/Ag3-thiolate core-shell particles
      for selective detection of cysteine and Pb(II).
AB  - Giant Au(I)@Ag2/Ag3-thiolate clusters with strong fluorescence (lambdaex 400 nm,
      lambdaem 564 nm, and quantum yield 8.3%) have been prepared in aqueous medium
      from glutathione and corresponding precursor salts at neutral pH under sunlight.
      An intriguing synergism between Au(I)core and Ag(0)shell imparts long-term
      stability to the fluorescent giant clusters (synthesized with a chemically green
      method) due to drifting of electron density towards core from shell. The strong
      fluorescence is selectively damped by cysteine (Cys) leaving aside all other
      essential amino acids ("Turn Off"). This quenched fluorescence is restored again
      on introducing Pb(II) ions in the system ("Turn On"). No other metal ion can
      cause such a recovery of the lost fluorescence. Such "Turn Off" and "Turn On"
      fluorescence helps in the design of a selective Cys as well as Pb(II) sensor in
      one pot. Detection of Cys and Pb(II) down to 5 * 10(-8) M and 15 * 10(-8) M,
      respectively, is possible following the present strategy.

PMID- 25052963
TI  - Tyrosine kinase inhibitors in cancer therapeutics: great expectations from small
      molecules.

PMID- 25052964
TI  - Venous thromboembolism (VTE): risk assessment in hospitalized patients.
AB  - OBJECTIVE: To determine the number of hospitalized patients at risk for
      developing venous thromboembolism (VTE) / deep vein thrombosis (DVT), identifying
      the most common risk factor and to document the use of thromboprophylaxis. STUDY
      DESIGN: Observational and cross-sectional study. PLACE AND DURATION OF STUDY:
      Chandka Medical College Hospital, Larkana, from October to December 2011.
      METHODOLOGY: A total of 170 patients underwent this study and these included 51
      (30%) from general medical, and 119 (70%) from surgical units. Inclusion and
      exclusion criteria were defined and data was collected on printed format. VTE
      risk assessment was done according to Caprini Model and criteria defined by the
      American College of Chest Physicians- ACCP. RESULTS: Out of 170 patients, 91 were
      male and 79 female with mean age of 39 +/- 16 years. According to ACCP criteria
      for VTE risk assessment, 20% (n=34) patients were identified to be at low risk,
      20% (n=34) at moderate risk, 47.65% (n=81) at high risk and 12.35% (n=21) at very
      high risk of developing VTE. The commonest risk factor significantly identified
      was immobility (54.7%, p < 0.005), followed by advancing age (41.17%, p < 0.005)
      and obesity (18.23%). The most common risk factor in all types of surgical
      patients was anaesthesia for more than 45 minutes 82.35% (n=98/119) and in
      medical patients advancing age 45% (n=23/51). Only 6 (3.5%) patients received
      thromboprophylaxis, all were surgical patients of very high-risk category.
      CONCLUSION: Majority of studied hospitalized patients were at high risk of
      developing VTE. Immobility was the commonest risk factor for developing VTE,
      followed by advancing age and obesity. Very few hospitalized patients actually
      received thromboprophylaxis.

PMID- 25052965
TI  - Validity of early parathyroid hormone assay as a diagnostic tool for sub-total
      thyroidectomy related hypocalcaemia.
AB  - OBJECTIVE: To determine the validity of early (one hour postoperatively)
      parathyroid hormone (PTH) assay (2 10 pg/ml), keeping gold standard as the serum
      ionic calcium level, for predicting sub-total thyroidectomy-related hypocalcaemia
      and to calculate the sensitivity and specificity of latent signs of tetany. STUDY
      DESIGN: Cross-sectional validation study. PLACE AND DURATION OF STUDY: Department
      of General Surgery, Pakistan Institute of Medical Sciences, Islamabad from August
      2008 to August 2010. METHODOLOGY: Patients undergoing sub-total thyroidectomy
      were included by convenience sampling. PTH assay was performed 1 hour post sub
      total thyroidectomy. Serum calcium levels were performed at 24 and 48 hours, 5th
      day and 2 weeks after surgery. Cases that developed hypocalcaemia were followed
      up for a period of 6 months with monthly calcium level estimation to identify
      cases of permanent hypocalcaemia. Symptoms and signs of hypocalcaemia manifesting
      in our patients were recorded. Data was analyzed through SPSS version 10. 2 x 2
      tables were used to calculate sensitivity and specificity of PTH in detecting
      post-thyroidectomy hypocalcaemia. RESULTS: Out of a total of 110 patients
      included in the study, 16.36% (n=18) developed hypocalcaemia including 1.81%
      (n=2) cases of permanent hypoparathyroidism. The sensitivity of one hour
      postoperative PTH assay as a predictive tool for post-thyroidectomy related
      hypocalcaemia was 94.4% while its specificity was 83.6% with 53% positive
      predictive value and 98.7% negative predictive value. CONCLUSION: One hour post
      sub-total thyroidectomy PTH assay can be helpful in predicting post sub-total
      thyroidectomy hypocalcaemia. Moreover, it can be useful in safe discharge of day
      care thyroidectomy patients.

PMID- 25052966
TI  - Influence of anthropometric measurements on abnormal gonadotropin secretion in
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the influence of anthropometric measurements on abnormal
      gonadotropin secretion in patients with polycystic ovary syndrome (PCOS). STUDY
      DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: The Institute of
      Basic Medical Sciences (IBMS), DUHS in collaboration with Gynae/infertility
      clinics of the Civil Hospital and Lady Dufferin Hospital, Karachi, from October
      2010 to February 2011. METHODOLOGY: One hundred and sixty three oligomenorrhic
      PCOS women of reproductive age (18 - 40 years) fulfilling the revised Rotterdam
      2003 criteria were studied. The data recorded on a prescribed proforma included
      current age, age at menarche, menstrual irregularities, presence of hirsuitism,
      acne, infertility, familial nature, blood pressure, BMI and waist-hip ratio.
      Blood samples for gonadotropin assay were taken randomly on day 6th to 30th of
      menstrual cycle, in a gel tube. Hormonal assay was performed using
      chemiluminescent immunoassay. Kruskul Wallis test was used to assess the
      influence of BMI levels on LH:FSH values. RESULTS: The mean weight was 66.14 +/-
      11.02 kg and mean BMI was 27.03 +/- 4.42 kg/m2. There was no significant
      difference in mean LH/FSH ratio (p=.575) among BMI groups. However, there was a
      positive correlation between BMI and LH:FSH ratio (p=0.04, r=0.155). CONCLUSION:
      There was high frequency of obesity (69%) in women with PCOS. Although no
      significant difference was found between mean LH:FSH ratio among different BMI
      groups levels but significant correlation between BMI levels and LH: FSH
      suggested that there was positive relation between BMI and LH: FSH.

PMID- 25052967
TI  - Immunological evaluation of beta-thalassemia major patients receiving oral iron
      chelator deferasirox.
AB  - OBJECTIVE: To determine the immune abnormalities and occurrence of infections in
      transfusion-dependent beta-thalassemia major patients receiving oral iron
      chelator deferasirox (DFX). STUDY DESIGN: An observational study. PLACE AND
      DURATION OF STUDY: Hematology Clinics, King Khalid University Hospital, Riyadh,
      Saudi Arabia, from July to December 2010. METHODOLOGY: Seventeen patients with
      beta-thalassemia major (12 females, median age 26 years) receiving deferasirox
      (DFX) for a median duration of 27 months were observed for any infections and had
      their immune status determined. Immune parameters studied included serum
      immunoglobulins and IgG subclasses, serum complement (C3 and C4) and anti-nuclear
      antibody (ANA) level, total B and T-lymphocytes, CD4+ and CD8+ counts, CD4+/CD8+
      ratio, and natural killer (NK) cells. Immunological parameters of the patients
      were compared with age, gender, serum ferritin level and splenectomy status.
      Lymphocyte subsets were also compared with age and gender matched normal
      controls. RESULTS: A considerable reduction in serum ferritin was achieved by DFX
      from a median level of 2528 to 1875 MUmol/l. Serum IgG levels were increased in 7
      patients. Low C4 levels were found in 9 patients. Total B and T-lymphocytes were
      increased in 14 patients each, while CD4+, CD8+ and NK cells were increased in
      13, 12 and 11 patients respectively. Absolute counts for all lymphocyte subsets
      were significantly higher compared to the normal controls (p 2 0.05 for all
      parameters). Raised levels of IgG were associated with older age, female gender,
      splenectomized status and higher serum ferritin levels but this did not reach
      statistical significance except for the higher ferritin levels (p=0.044).
      Increased tendency to infections was not observed. CONCLUSION: Patients with beta
      thalassemia major receiving DFX exhibited significant immune abnormalities.
      Changes observed have been described previously, but could be related to DFX. The
      immune abnormalities were not associated with increased tendency to infections.

PMID- 25052968
TI  - Clinical presentations of acute leukemia.
AB  - OBJECTIVE: To document the clinical presentation and epidemiology of various
      types of acute leukemia with their respective referral source at a tertiary level
      centre in Peshawar. STUDY DESIGN: An observational study. PLACE AND DURATION OF
      STUDY: Department of Pathology, Hayatabad Medical Complex (HMC), Peshawar, from
      January 2011 to May 2012. METHODOLOGY: A total of 618 bone marrow biopsy reports
      were reviewed. All biopsy reports labeled as acute leukemia were reviewed for
      age, gender, address, referring unit, diagnosis on bone marrow examination,
      presenting complaints, duration of illness and findings of clinical examination.
      RESULTS: Ninety-two patients were diagnosed as suffering from acute leukemias
      (15%). ALL was most prevalent (46%), followed by AML (38%) and undifferentiated
      acute leukemia (16%). Males were affected more compared to females (60% vs. 40%).
      ALL and AML were predominant in pediatric (64%) and adults (77%) patients
      respectively. Patients from Afghanistan accounted for 33% of all cases followed
      by Peshawar (14%). Fever (77%), pallor (33%) and bleeding disorders (23%) were
      the main presenting complaints. Enlargement of liver, spleen and lymph nodes
      together was associated with ALL compared with AML (p = 0.004). CONCLUSION: ALL
      L1 and AML-M4 were the most common sub-types. Fever, pallor and bleeding
      disorders were the main presenting complaints. Enlargement of liver, spleen and
      lymph nodes was more frequently associated with ALL compared to AML.

PMID- 25052969
TI  - Quality of life in patients with thalassemia major in a developing country.
AB  - OBJECTIVE: To determine the problems faced by thalassemic patients in their
      personal, psychological and social life. STUDY DESIGN: A cross-sectional multi
      centre survey. PLACE AND DURATION OF STUDY: Karachi, Lahore and Quetta Centres of
      Fatimid Foundation, from October 2009 to October 2010. METHODOLOGY: An
      indigenously developed Qualifty of Life (QoL) questionnaire modified from SF-36
      questionnaire was administered to 101 transfusion dependent subjects suffering
      from thalassemia major. Variables were analyzed using SPSS version 15 for
      descriptive statistics. RESULTS: The mean age of the subjects was 10.5 years
      ranging from 6 - 21 years. Less than one third of the patients felt that their
      health was slightly worse as compared to last year. Forty five (44%) of the
      patients felt loneliness due to their disease. Parents of 36 (35.6%) of the
      children at times did not allow their children to play because of their disease.
      Twenty eight (27.7%) stated difficulty in mingling with children of their age.
      Seventy one (70.3%) of the patients reported that at some or all times they were
      worried about their future life and career while 70 (69.3%) admitted being taken
      extra care of by their friends and 56 (55.4%) by their teachers. CONCLUSION: The
      quality of life of surveyed thalassemic patients was immensely affected. Having
      physical impairments, social stresses, financial burdens and problems with their
      education and career make them very much vulnerable to psychological trauma very
      early in their life. All of this creates a hindrance in their way of developing
      into autonomous functioning adults.

PMID- 25052970
TI  - Inducible clindamycin resistance in Staphylococcus species.
AB  - OBJECTIVE: To determine the frequency of inducible clindamycin resistance in
      clinical isolates of Staphylococcus species by phenotypic D-test. STUDY DESIGN:
      Observational study. PLACE AND DURATION OF STUDY: Ziauddin University Hospital,
      Karachi, from July to December 2011. METHODOLOGY: Consecutive clinical isolates
      of Staphylococcus species were collected and identified by conventional
      microbiological techniques. Antimicrobial susceptibility testing and inducible
      clindamycin resistance was carried out by performing D-test using CLSI criteria.
      Methicillin resistance was detected by using Cefoxitin disk as a surrogate
      marker. Statistical analysis was performed by SPSS version-17. RESULTS: A total
      of 667 clinical isolates of Staphylococcus species were obtained during the study
      period. In these isolates, 177 (26.5%) were Staphylococcus aureus, and 490
      (73.5%) were coagulase negative Staphylococci. The total frequency of inducible
      clindamycin resistance among isolates of Staphylococcus species was 120/667
      (18%). Frequency of inducible clindamycin resistance among coagulase negative
      Staphylococci group and Staphylococcus aureus group were 18.57% and 16.38%
      respectively. Median age of patients in D-test positive group was 19.5 (1 - 54)
      years. CONCLUSION: The frequency of inducible clindamycin resistance among
      Staphylococcus species may differ in different hospital setup. Clinical
      microbiology laboratories should implement testing simple and effective D-test on
      all Staphylococcus species. D-test positive isolates should be reported
      clindamycin resistant to decrease treatment failure.

PMID- 25052971
TI  - Overhanging amalgam restorations by undergraduate students.
AB  - OBJECTIVE: To determine the frequency of overhanging margins in amalgam
      restorations done by undergraduate students at Fatima Jinnah Dental College
      Hospital, Karachi. STUDY DESIGN: Observational study. PLACE AND DURATION OF
      STUDY: Department of Operative Dentistry, Fatima Jinnah Dental Hospital, Karachi,
      from January to June 2009. METHODOLOGY: Patients aged 20 - 45 years attending the
      Department of Operative Dentistry requiring class-II restorations were included
      in the study. Whereas, third molars, overlapped proximal surfaces, teeth adjacent
      to edentulous spaces and pregnant females were excluded. One hundred and fifty
      patients were selected randomly aged between 20 - 45 years requiring class-II
      restorations. Posterior Bitewing radiographs were taken and 1600 surfaces were
      examined. Restorations were done by undergraduate students at Fatima Jinnah
      Dental College Hospital, Karachi. Chi-square test was utilized to analyze the
      relationship between location and surface of overhang. RESULTS: Overhanging
      amalgam restorations were common in the restorations done by undergraduate
      students (58%). The occurrence of overhangs was more frequent on the distal
      surfaces (56%) Although the association of amalgam overhangs with the surfaces of
      the teeth was significant (p < 0.0001), overhangs were not significantly
      associated with the location of the teeth (p < 0.063). CONCLUSION: Overhanging
      restorations were present in approximately 58% of all proximal amalgam
      restorations done by undergraduate students.

PMID- 25052972
TI  - Effects of pre-operative submucosal dexamethasone injection on the postoperative
      swelling and trismus following surgical extraction of mandibular third molar.
AB  - OBJECTIVE: To determine the effects of pre-operative submucosal dexamethasone
      injection on postoperative swelling and trismus following surgical extraction of
      mandibular third molar. STUDY DESIGN: Randomized controlled trial. PLACE AND
      DURATION OF STUDY: Department of Oral and Maxillofacial Surgery, Armed Forces
      Institute of Dentistry (AFID), Rawalpindi, from October 2009 to March 2010.
      METHODOLOGY: A total of 100 patients aged 18 - 40 years with good periodontal
      health and mesioangular impaction were divided in two treatment groups (50 in
      each group). Group-A received prophylactic 4 mg submucosal dexamethasone
      intraoral injection and Group-B acted as control group. Facial swelling and
      trismus were assessed at baseline, 2nd and 7th postoperative days. Data was
      analyzed using SPSS-10. RESULTS: There were 35 (70%) males and 15 (30%) females
      in group-A and 34 (68%) males and 16 (32%) females in group-B. Surgical time
      ranged from 30 - 50 minutes (mean = 40.62 +/- 4.886 minutes) for group-A and 33 -
      50 minutes (mean = 42.12 +/- 4.543 minutes) for group-B. Administration of
      dexamethasone had statistically significant effect in reduction of swelling and
      trismus on second postoperative day (p < 0.05) in group-A. CONCLUSION: Pre
      operative 4 mg submucosal dexamethasone injection was significantly effective in
      reduction of postoperative swelling and trismus.

PMID- 25052973
TI  - Implementing WHO feeding guidelines for inpatient management of malnourished
      children.
AB  - OBJECTIVE: To evaluate the efficacy of adopting WHO feeding guidelines on weight
      gain and case fatality rate in malnourished children. STUDY DESIGN: Cross
      sectional, observational study. PLACE AND DURATION OF STUDY: Department of
      Pediatrics, Dow University of Health Sciences, Karachi, from 2009 to 2010.
      METHODOLOGY: Patients above 6 months and less than 5 years of age with severe
      malnutrition were included during the study period, acute complications were
      treated and nutritional rehabilitation by WHO feeding formulae was done.
      Demographic details, clinical features, reasons for weight gain and risk factors
      of mortality were analyzed. RESULTS: A total of 131 children were included. Mean
      age of children was 22 +/- 18 months. There were 78% marasmic, 4% kwashiorkor and
      marasmic kwashiorkor 18% children. Resolution of edema took 8 +/- 4 days,
      dermatosis cleared in 11 +/- 3 days. Mean hospital stay was 10 +/- 8 days. Case
      fatality rate was 13%. Mean weight gain was 5.25 +/- 4.57 g/kg/day. Weight gain
      of > 5 gm/kg/day was associated with hospital stay of more than 7 days,
      acceptability and palatability of feed by the children and mothers and early
      clearance of infections. CONCLUSION: Implementation of WHO feeding guidelines
      resulted in adequate weight gain of inpatient malnourished children, however,
      adequate healthcare services are available at the therapeutic feeding centers.

PMID- 25052974
TI  - Clinical and biochemical characteristics of children with juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To determine the clinical and biochemical characteristics of children
      with Juvenile Idiopathic Arthritis (JIA) at a tertiary care centre in Karachi,
      Pakistan. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY:
      Paediatric Rheumatology Clinic of The Aga Khan University Hospital (AKUH),
      Karachi, from January 2008 to December 2011. METHODOLOGY: Clinical and laboratory
      profile and outcome of children less than 15 years of age attending the
      Paediatric Rheumatology Clinic of the Aga Khan University, Karachi with the
      diagnosis of Juvenile Idiopathic Arthritis according to International League
      against Rheumatism were studied. These children were classified into different
      types of JIA; their clinical and laboratory characteristics, response to therapy
      and outcome was evaluated. RESULTS: Sixty eight patients satisfying the criteria
      of International League against Rheumatism (ILAR) for Juvenile Idiopathic
      Arthritis were enrolled during the study period of four consecutive years, their
      age ranged from 9 months to 15 years. Mean age at onset was 6.45 +/- 4.03 years
      while mean age at diagnosis was 7.60 +/- 3.93 years. Polyarticular was the most
      predominant subtype with 37 (54%) patients, out of these, 9 (24%) were rheumatoid
      factor positive. An almost equal gender predisposition was observed. Fever and
      arthritis were the most common presenting symptoms, with only 2 patients
      presenting with uveitis. CONCLUSION: The clinico-biochemical characteristics of
      JIA at the study centre showed a pattern distinct with early onset of disease,
      high frequency of polyarticular type and a higher rheumatoid factor (QRA) and ANA
      positivity in girls.

PMID- 25052975
TI  - Frequency of gingival display during smiling and comparison of biometric
      measurements in subjects with and without gingival display.
AB  - OBJECTIVE: To determine the frequency of gingival display during smiling and to
      compare biometric measurements in subjects with and without gingival display.
      STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of
      Prosthodontics, Dr. Ishrat-ul-Ibad Khan Institute of Oral Health Sciences, Dow
      University of Health Sciences, Karachi, from October 2012 to March 2013.
      METHODOLOGY: A total of 275 subjects (121 men and 154 women) were included in
      this study. The age of the participants ranged between 21 and 65 years.
      Measurements were carried out using digital caliper. For each participants, the
      gingival display was judged as either visible or not. The amounts of horizontal
      and vertical overlap of anterior teeth were measured using a digital caliper.
      Gender differences in these parameters and the relationship between subjects
      showing gingival display when smiling and the two intraoral dental biometric
      measurements were determined. Statistical analyses of data were performed using
      SPSS version 17.0 software. The mean scores for gender were calculated and a
      Student's t-test was used to identify significant differences between both
      groups. Significant level was set to 0.05. RESULTS: A relatively small percentage
      of the subjects (37.8%) displayed gingiva when smiling. More women significantly
      displayed gingiva when smiling than men, with a 2:1 female: male ratio. Women had
      significantly (p=0.001) more horizontal overlap (3.34 +/- 1.45 mm) than men (2.90
      +/- 1.44 mm), although no significant gender difference were found in vertical
      overlap. Subjects with gingival display had significantly (p < 0.05) more
      horizontal (3.49 +/- 1.36 mm) and vertical (3.26 +/- 1.47 mm) overlap of anterior
      teeth compared to those who did not display gingiva when smiling. CONCLUSION:
      Significantly more women displayed gingiva in smiling. Women had significantly
      more horizontal overlap than men. No gender differences were recorded between
      vertical overlap. Subjects who displayed gingiva when smiling had more horizontal
      and vertical overlap of anterior teeth.

PMID- 25052976
TI  - Therapeutic use of hyperbaric oxygen therapy for children with autism spectrum
      disorder.
AB  - Autism spectrum disorder (ASD) is neurodevelopment disorder, characterized by
      impairment in social interaction, verbal and non-verbal communication and the
      presence of restricted and repetitive stereotyped behaviors. The condition
      manifests within the first 3 years of life and persists till adulthood. At
      present, the etiology of ASD is largely unknown, but genetic, environmental,
      immunological, and neurological factors are thought to play a role in the
      development of ASD. The prevalence of ASD has increased dramatically in the past
      few decades. According to current estimates from the United States Centers for
      Disease Control and Prevention (CDC) as many as 1 in 91 children have ASD in USA.
      Studies from the Middle East on this topic are limited. Autism in Saudi Arabia is
      slightly higher than reported in the developed countries. Hyperbaric oxygen
      therapy (HBOT) has been growing in popularity for the treatment of ASD over
      recent years. However, few studies of its effectiveness have been reported. This
      article reviews important publications regarding the physiologic and clinical
      influence of HBO on ASD. Several case series and randomized trials have all
      proposed that low pressure/ low oxygen concentration hyperbaric treatment can
      improve the clinical manifestations of autism. 

PMID- 25052977
TI  - Are medical undergraduates more likely to indulge in substance abuse than non
      medical undergraduates? A survey from Karachi.
AB  - OBJECTIVE: To determine frequency of substance abuse and the commonest substance
      of abuse among medical and non-medical undergraduates. STUDY DESIGN: Survey
      report. PLACE AND DURATION OF STUDY: Dow International Medical College, Karachi,
      from June 2012 to August 2012. METHODOLOGY: Semester VIII students from Dow
      International Medical College, Dow University of Health Sciences who visited the
      selected medical and non-medical universities, data collected through self
      responding questionnaire which was handed out to the participants. Data was
      collected from 4 medical and 4 non-medical universities. All responding
      undergraduate students in selected universities were included. Data was
      maintained and analyzed on SPSS version 16 for descriptive statistics. RESULTS:
      Total number of responders was 572 with male: female ratio of 1.23: 1.0 and mean
      age of 21.76 +/- 2.168 years. Frequency of regular substance abuse was 20.1%.
      Males were abusing substance more than females, ratio being 4.7: 1.0 among
      abusers. The most common substance of abuse was tobacco. Frequency of regular
      substance abuse in nonmedical undergraduates was 29.4% which was higher than
      medical graduates (13.4%). CONCLUSION: Substance abuse among undergraduates in
      selected universities in Karachi was overall 20.1%. Male nonmedical
      undergraduates were more frequently using such substances; tobacco being the most
      common.

PMID- 25052978
TI  - Updating teaching and learning methodologies in radiology.

PMID- 25052979
TI  - Fatal primary meningoencephalitis caused by Naegleria fowleri.
AB  - Naegleria fowleri is a free living parasite which habitats in fresh water
      reservoirs. It causes a fatal nervous system infection known as primary amoebic
      meningoencephalitis by invading through cribriform plate of nose and gaining
      entry into brain. We report a case of primary amoebic meningoencephalitis caused
      by Naegleria fowleri in Karachi, Pakistan, in a 42 years old male poultry farm
      worker having no history of swimming. Clinical course was fulminant and death
      occurred within one week of hospital admission. Naegleria fowleri was detected by
      wet mount technique in the sample of cerebrospinal fluid collected by lumbar
      puncture of patient. This is a serious problem and requires immediate steps to
      prevent general population to get affected by this lethal neurological infection.

PMID- 25052980
TI  - Tracheal rhinosporidiosis: an uncommon life threatening benign condition.
AB  - Rhinosporidiosis in tracheobronchial tree is extremely rare. It poses diagnostic
      and therapeutic challenges and has high chance of mortality because of
      presentation with respiratory distress. We report such a case of a 35 years old
      man who presented with respiratory distress and dry irritating cough. Fiberoptic
      laryngoscopy revealed a reddish soft tissue mass below the vocal cord level.
      Magnetic Resonance Imaging showed a soft tissue opacity within the trachea
      occluding the airway. Direct endoscopic biopsy was done after securing the
      airway. Histopathological examination confirmed rhinosporidiosis and the mass was
      excised through an external approach. The patient was free of symptoms and no
      recurrence was reported till 30 months of follow-up. 

PMID- 25052981
TI  - Epiglottic hypoplasia: a natural model for supraglottic laryngoplasty.
AB  - Non-syndromic hypoplasia of the epiglottis presenting without symptoms at middle
      age is an extremely rare entity. We report a 50 years female who presented with
      oral ulcers and incidentally was found to have an asymptomatic rudimentary
      epiglottis and thickened bilateral aryepiglottic folds forming an inverted funnel
      shaped supraglottis protecting the airway from any aspiration. This case
      demonstrated a functional model of natural supraglottic laryngoplasty which can
      be used in treating intractable aspiration, similar to the Steam boat
      modification of Biller's technique of supraglottic laryngoplasty. This natural
      example can be used to design or scrutinize the existing models of supraglottic
      laryngoplasty in the treatment of intractable aspiration. 

PMID- 25052982
TI  - Occurrence of extended-spectrum b-lactamase producers among enterobacteriaceae in
      a paediatric tertiary care facility in Kabul.
AB  - The aim of this study was to determine the occurrence of extended spectrum beta
      lactamase (ESBL)-producing species of Enterobacteriaceae to control their spread,
      from March 2008 to June 2012. A total of 411 ESBL-producing isolates were
      reported belonging to the family Enterobacteriaceae. There were 235 (57.18%)
      hospital-acquired infections (HAIs) and 176 (42.82%) community-acquired
      infections (CAIs). Out of total isolates, majority were E. coli (n=165, 40.15%),
      followed by 38.93% Klebsiella spp. (n=161), 9.97% Enterobacter spp. (n=41) and
      6.33% Serratia spp. (n=26). Amongst HAIs, most frequent i.e., 111/235 (47.23%)
      were Klebsiella spp, whereas, amongst CAIs, majority i.e., 96/176 (54.55%) were
      E. coli. The frequency of ESBL-producing isolates from different sites was blood
      (37.71%), urine (29.93%), respiratory tract (18.49%) and other sites including
      pus/pus swabs, CSF/body fluids and secretions (13.87%) respectively. Majority of
      blood stream infections were caused by ESBL-producing Klebsiella species which
      accounted for 55.48% of all cases who had septicaemia, whereas E. coli was
      responsible for causing majority of urinary tract infections (UTIs) and accounted
      for 78% of all UTIs cases. Intensive Care Unit (ICU) was the place where majority
      of infections (55%) were observed, followed by 29% in the Medical Unit and 16% in
      the Surgical Unit. 

PMID- 25052983
TI  - Research in emergency medicine in Pakistan: the need for a strategic approach.

PMID- 25052984
TI  - Frequently isolated bacteria and their culture and sensitivity pattern in a
      medical ICU.

PMID- 25052985
TI  - Retained silicone dome from open fit hearing aid: an unwanted and under
      recognized aural foreign body.

PMID- 25052986
TI  - Shifting of vitamin D deficiency to hypervitaminosis and toxicity.

PMID- 25052987
TI  - A review on antiproliferative and apoptotic activities of natural honey.
AB  - Recent statistics revealed that cancer is one among the main reasons for death
      throughout the world. Several treatments are available but still there is no cure
      when it is detected at late stages. One of the treatment modes for cancer is
      chemotherapy which utilizes anticancer drugs in order to eradicate the cancer
      cells by apoptosis. Apoptosis is a programmed cell death through which body
      maintains homeostasis or kills cancer cells by utilizing its cell machinery.
      Recent researches have concluded that dietary agents have a putative role in
      instituting apoptosis of cancer cells. Honey, one of the victuals rich in
      antioxidants, has a long-standing exposure to humans and its role in cancer
      prevention and treatment is a topic of current interest. Various researchers have
      been experimenting honey against different cancers and provided valuable insights
      about the apoptosis induced by the honey. This review will highlight the recent
      findings of apoptotic mechanism involved in different cancer cells. Further it
      also reports antitumor activity of honey in some animal models. Hence it is high
      time to initiate more preclinical trials as well as clinical experiments which
      would further add to the knowledge of anticancer nature of honey and also endorse
      honey as a potential candidate in the war against cancer. 

PMID- 25052988
TI  - In search of natural remediation for cervical cancer.
AB  - Cancer is a serious global health issue. Cancer of the cervix is one of the
      leading gynecological malignancies worldwide; though it is more prevalent in the
      developing countries. Fruitful approaches are needed to control cervical cancer.
      Awareness through proper education, screening and early detection may pave a way
      to combat the disease process in the first place. Surgery, chemotherapy and
      radiotherapy are some of the common modes of treatment for cervical cancer.
      Conventional medical treatments often are not able to eliminate the offending
      growth fully and are not free from complications. Side effects very often are
      disastrous. Therefore, it is high time to focus our attention to bring about a
      novel way to tackle the problem. Advocating holistic approach using plant derived
      phytochemicals may address this health problem. These molecules show potent
      anticancer potential and are free from toxicity. Adjunctive therapies using
      phytochemicals may prove to be of tremendous importance. Plants are a prime
      source of effective drugs for the treatment of various forms of cancer. Many of
      these compounds are well characterized and have led the researchers to develop
      potential chemotherapeutic agents. Neutraceuticals may not replace the
      conventional treatment regimen, but they may enhance the efficacy of chemotherapy
      and radiotherapy. 

PMID- 25052989
TI  - Denbinobin upregulates miR-146a expression and attenuates IL-1beta-induced
      upregulation of ICAM-1 and VCAM-1 expressions in osteoarthritis fibroblast-like
      synoviocytes.
AB  - Interleukin-1beta (IL-1beta) upregulates intercellular adhesion molecule-1 (ICAM
      1) and vascular cell adhesion molecule-1 (VCAM-1) expressions in osteoarthritis
      fibroblast-like synoviocytes (OA-FLS) via nuclear factor (NF)-kappaB-mediated
      mechanism; enhancement of leukocyte infiltration and upregulation of
      proinflammatory mediators play a crucial role in OA pathophysiology. MicroRNA
      (miR)-146a suppresses inflammatory responses by inhibiting NF-kappaB activity and
      target gene expression, and epigenetic mechanisms are reportedly involved in miR
      expression regulation. Here, we aimed to verify the inhibition of ICAM-1/VCAM-1
      expression in OA-FLS on denbinobin treatment and to determine whether this
      inhibition was due to the miR-146a-dependent pathway. We also assessed the
      epigenetic regulation caused by histone acetyltransferases involved in denbinobin
      action. Denbinobin attenuated the upregulation of IL-1beta-induced ICAM-1/VCAM-1
      expression and monocyte adhesion to OA-FLS. The mechanism underlying the
      inhibitory effects of denbinobin involved miR-146a induction, which in turn
      inhibited NF-kappaB signaling. This is because miR-146a inhibitor abrogated the
      inhibitory effects of denbinobin. Furthermore, histone acetyltransferase
      inhibitor attenuated the denbinobin-induced upregulation of miR-146a expression
      and inhibited the acetylation of NF-kappaB-binding sites located within the miR
      146a promoter region. These data suggest that an epigenetic mechanism plays a
      crucial role in the upregulation of miR-146a expression in response to denbinobin
      treatment. Our overall findings suggest that denbinobin can be used as a potent
      anti-inflammatory agent. KEY MESSAGE: Denbinobin inhibited IL-1beta-induced ICAM
      1/VCAM-1 expression and monocyte adhesion to OA-FLS. It was due to denbinobin
      increased miR-146a level, which in turn inhibited NF-kappaB signaling. Our
      overall findings suggest that denbinobin can be used as a potent anti
      inflammatory agent.

PMID- 25052990
TI  - Egr-1 mRNA expression is a marker for the direction of mammalian ocular growth.
AB  - PURPOSE: The immediate early gene Egr-1 is thought to form part of the pathway
      that mediates abnormal ocular growth. This study investigated whether the mRNA
      expression levels of Egr-1 in a mammalian retina are modulated differentially,
      depending on the direction of ocular growth. METHODS: To induce accelerated
      growth and myopia, guinea pigs wore a -5 diopter (D) lens over one eye from 4 to
      11 days of age. To induce inhibited growth, the lens was removed after 7 days of 
      5 D lens wear, and the eye allowed to recover from myopia for 3 days. Ocular
      parameters and Egr-1 mRNA levels were subsequently assessed, and compared to
      untreated fellow eyes and eyes from untreated littermates. Possible circadian
      changes in Egr-1 mRNA levels were also determined in 18 additional animals by
      taking measures every 4 hours during a 24-hour cycle. RESULTS: Ocular
      compensation to a -5 D lens occurred after 7 days (Delta -4.8 D, Delta +147 MUm
      growth, N = 20). In 5 highly myopic eyes (Delta -7.4 D), Egr-1 mRNA levels in the
      retina were significantly downregulated relative to contralateral control (51%)
      and age-matched untreated (47%) eyes. Three days after the -5 D lens was removed,
      eyes had recovered from the myopia (Delta -0.5 D, relative change of +2.9 D, N =
      4) and Egr-1 mRNA levels were significantly elevated relative to contralateral
      (212%) and untreated (234%) eyes, respectively. Normal Egr-1 mRNA expression was
      higher in the middle of the day than in the middle of the night. Immunolabeling
      showed strong Egr-1 reactivity in cell bodies in the inner nuclear and ganglion
      cell layers. CONCLUSIONS: Egr-1 mRNA levels in a mammalian retina show a bi
      directional persistent response to opposing ocular growth stimuli. This suggests
      retinal Egr-1 might act as a signal for the direction of ocular growth in
      different species.

PMID- 25052991
TI  - Measurement of subfoveal choroidal thickness after cataract surgery in enhanced
      depth imaging optical coherence tomography.
AB  - PURPOSE: To compare subfoveal choroidal thickness (SFCT) before and after
      uneventful cataract surgery using enhanced depth imaging optical coherence
      tomography (EDI-OCT). METHODS: A prospective study was conducted on 115 eyes of
      95 patients who had phacoemulsification. Measurements of SFCT were performed
      preoperatively, 1 day (D1), 7 days (D7), 1 month (M1), and 3 months (M3) after
      surgery using the EDI-OCT technique. Central retinal thickness (CRT) was measured
      before surgery and at M1 and M3. RESULTS: The 95 patients had a mean age of 76 +/
      8.3 years. The mean SFCT at baseline was 224 +/- 75 MUm. It showed a negative
      correlation with age and axial length (P = 0.03). The SFCT significantly
      increased after surgery with a mean value of 232 +/- 76 MUm at D1 (P < 0.001),
      237 +/- 78 MUm at M1 (P < 0.001), and 232 +/- 76 MUm at M3 (P < 0.001). The mean
      CRT increased from 234 +/- 48 MUm at baseline to 248 +/- 48 MUm at M1 (P =
      0.005), and 252 +/- 81 MUm at M3 (P = 0.001). Three (2.6%) patients developed a
      pseudophakic cystoid macular edema (PCME). The greatest progression of SFCT after
      phacoemulsification was observed for these patients. It preceded the occurrence
      of pseudophakic cystoid macular edema (PCME) by 1 month. CONCLUSIONS: Mean SFCT
      increased after cataract surgery. The changes in baseline SFCT were greater in
      PCME patients and preceded the increase in CRT.

PMID- 25052992
TI  - Reading ability and reading engagement in older adults with glaucoma.
AB  - PURPOSE: We evaluated the impact of glaucoma-related vision loss on reading
      ability and reading engagement in 10 reading activities. METHODS: A total of 63
      glaucoma patients and 59 glaucoma suspect controls self-rated their level of
      reading difficulty for 10 reading items, and responses were analyzed using Rasch
      analysis to determine reading ability. Reading engagement was assessed by asking
      subjects to report the number of days per week they engaged in each reading
      activity. Reading restriction was determined as a decrement in engagement.
      RESULTS: Glaucoma subjects more often described greater reading difficulty than
      controls for all tasks except puzzles (P < 0.05). The most difficult reading
      tasks involved puzzles, books, and finances, while the least difficult reading
      tasks involved notes, bills, and mail. In multivariable weighted least squares
      regression models of Rasch-estimated person measures of reading ability, less
      reading ability was found for glaucoma patients compared to controls (beta = 
      1.60 logits, P < 0.001). Among glaucoma patients, less reading ability was
      associated with more severe visual field (VF) loss (beta = -0.68 logits per 5-dB
      decrement in better-eye VF mean deviation [MD], P < 0.001) and contrast
      sensitivity (beta = -0.76 logits per 0.1-unit lower log CS, P < 0.001). Each 5-dB
      decrement in the better-eye VF MD was associated with book reading on 18% fewer
      days (P = 0.003) and newspaper reading on 10% fewer days (P = 0.008). No
      statistically significant reading restriction was observed for other reading
      activities (P > 0.05). CONCLUSIONS: Glaucoma patients have less reading ability
      and engage less in a variety of different reading activities, particularly those
      requiring sustained reading. Future work should evaluate the mechanisms
      underlying reading disability in glaucoma to determine how patients can maintain
      reading ability and engagement.

PMID- 25052993
TI  - Simultaneous investigation of vascular and retinal pigment epithelial pathologies
      of exudative macular diseases by multifunctional optical coherence tomography.
AB  - PURPOSE: To investigate exudative macular disease, multifunctional optical
      coherence tomography (MF-OCT) using a 1-MUm probe band was developed. The
      clinical utility of MF-OCT was examined in a descriptive case series. METHODS:
      Ten eyes of nine subjects with exudative macular disease, including one eye with
      age-related macular degeneration (AMD), one eye with idiopathic neovascular
      maculopathy, and eight eyes with polypoidal choroidal vasculopathy (PCV), were
      investigated. Areas of 6 * 6 mm(2) around the pathologic region were scanned with
      512 * 1024 depth scans in 6.6 seconds. Structural OCT, Doppler optical coherence
      angiography (OCA), and cumulative phase retardation images were obtained with a
      single measurement. Each MF-OCT image visualized the structure, vasculature, and
      birefringence. Degree of polarization uniformity values were also obtained for
      selective visualization of the retinal pigment epithelium (RPE). The MF-OCT
      images were compared with conventional ophthalmic images. RESULTS: Abnormal
      vasculatures were observed with Doppler OCA in all eyes, which presented high
      similarity to indocyanine green angiography in the midphase. The RPE and
      exudation in the pathologic regions were discriminated in one eye with AMD and
      five of eight eyes with PCV. Cumulative phase retardation visualized fibrosis
      scars in two of the PCV cases. CONCLUSIONS: Multifunctional OCT revealed depth
      resolved abnormal vasculatures, the integrity of the RPE and choroid,
      discrimination of the RPE and exudation, and existence of fibrosis scars in
      exudative macular diseases. Interpretation of MF-OCT examination is well matched
      with conventional ophthalmic examination. These results suggest that MF-OCT can
      be used as a noninvasive ophthalmic examination tool prior to conventional
      examinations in clinical routines.

PMID- 25052994
TI  - Age-related changes in human corneal epithelial thickness measured with anterior
      segment optical coherence tomography.
AB  - PURPOSE: To measure corneal and limbal epithelial thickness (ET) in normal
      subjects and to evaluate its variation with age by using anterior segment optical
      coherence tomography (AS-OCT). METHODS: A total of 180 normal subjects (180
      healthy eyes) were enrolled and divided into four groups according to age: A (0
      20 years), B (21-40 years), C (41-60 years), and D (>60 years). Cornea and limbus
      were imaged with OCT. Corneal ET (CET) was obtained automatically by the built-in
      analysis software of the OCT system. Limbal ET (LET) in four quadrants was
      manually measured from OCT images. RESULTS: Corneal ET of a central 2-mm diameter
      zone in groups A, B, C, and D were 53.4 +/- 2.8 MUm, 53.4 +/- 2.7 MUm, 53.2 +/-
      3.0 MUm, and 52.9 +/- 3.3 MUm, respectively, N showing no significant change with
      aging. In the paracentral zone extending to 6-mm diameter, correlation analysis
      suggested that CET was inversely associated with age (P < 0.05). Limbal ET in the
      nasal and the temporal quadrants were similar and decreased with aging, the
      averages were 58.3 +/- 8.1 MUm, 54.1 +/- 6.1 MUm, 51.2 +/- 6.1 MUm, 51.6 +/- 5.2
      MUm for groups A, B, C and D, respectively; while age seemed to have no effect on
      LET of the superior and the inferior quadrant. CONCLUSIONS: The paracentral
      corneal epithelium, as well as the nasal and temporal limbal epithelium, became
      thinner with aging, while the central CET seemed to remain constant. Measurement
      with AS-OCT of the corneal and limbal ET could aid in clinical assessment and
      planning treatments of the cornea.

PMID- 25052995
TI  - The effect of standard and high-fluence corneal cross-linking (CXL) on cornea and
      limbus.
AB  - PURPOSE: When treating peripheral ectatic disease-like pellucid marginal
      degeneration (PMD), corneal cross-linking with UV-A and riboflavin (CXL) must be
      applied eccentrically to the periphery of the lower cornea, partly irradiating
      the corneal limbus. Here, we investigated the effect of standard and double
      standard fluence corneal cross-linking with riboflavin and UV-A (CXL) on cornea
      and corneal limbus in the rabbit eye in vivo. METHODS: Epithelium-off CXL was
      performed in male New Zealand White rabbits with two irradiation diameters (7 mm
      central cornea, 13 mm cornea and limbus), using standard fluence (5.4 J/cm(2))
      and double-standard fluence (10.8 J/cm(2)) settings. Controls were subjected to
      epithelial removal and riboflavin instillation, but were not irradiated with UV
      A. Following CXL, animals were examined daily until complete closure of the
      epithelium, and at 7, 14, 21, and 28 days. Animals were killed and a
      corneoscleral button was excised and processed for light microscopy and
      immunohistochemistry. RESULTS: For both irradiation diameters and fluences
      tested, no signs of endothelial damage or limbal vessel thrombosis were observed,
      and time to re-epithelialization was similar to untreated controls. Histological
      and immunohistochemical analysis revealed no differences in the p63 putative stem
      cell marker expression pattern. CONCLUSIONS: Even when using fluence twice as
      high as the one used in current clinical CXL settings, circumferential UV-A
      irradiation of the corneal limbus does not alter the regenerative capacity of the
      limbal epithelial cells, and the expression pattern of the putative stem cell
      marker p63 remains unchanged. This suggests that eccentric CXL may be performed
      safely in PMD.

PMID- 25052996
TI  - Loss of calpastatin leads to activation of calpain in human lens epithelial
      cells.
AB  - PURPOSE: Activation of calpains (calpain 2 and Lp82) in rodent lenses readily
      causes proteolysis and cataract formation. In contrast, primate lenses are quite
      resistant to activation of calpains. The hypothesis is that high levels of human
      endogenous calpain inhibitor, calpastatin (CS), prevent calpain activation in
      human lenses. The purpose of the present study was to directly test if CS is a
      major inhibitory factor in a human lens epithelial cell line, HLE B-3. METHODS:
      Small interfering RNAs (siRNAs) were used to knock down expression of CS in HLE B
      3. The cells then were cultured with the calcium ionophore, ionomycin, with or
      without a calpain inhibitor SNJ-1945. Transcripts for calpain 2 and CS were
      measured by quantitative PCR (qPCR). Calpain 2 activity was detected by
      immunoblotting for the calpain-specific, alpha-spectrin breakdown product and for
      activation-associated, fragments of calpain 2. RESULTS: Expression of CS in HLE B
      3 was remarkably higher than in alpha-TN4 (mouse comparator cell line).
      Proteolysis of alpha-spectrin was observed in the soluble proteins from alpha-TN4
      incubated with Ca(2+), but not in the human HLE B-3. When CS-reduced HLE B-3
      cells (transfected with CS siRNA) were cultured with ionomycin, calpain 2 was
      activated, specific proteolysis of alpha-spectrin occurred, and cell death
      ensued; SNJ-1945 inhibited these changes. CONCLUSIONS: Our data demonstrated that
      the high levels of endogenous CS do, indeed, inhibit calpain activity in normal
      human lens epithelial cells. We speculate that age-related oxidation might cause
      loss of CS activity in human lens epithelial cells, allowing activation of long
      dormant calpain 2, proteolysis of critical cytoskeletal proteins, and cataract
      formation.

PMID- 25052997
TI  - Choroid, Haller's, and Sattler's layer thickness in intermediate age-related
      macular degeneration with and without fellow neovascular eyes.
AB  - PURPOSE: To analyze choroidal, Sattler's, and Haller's layer thickness maps in
      age-related macular degeneration (AMD) patients having eyes with bilateral large
      drusen and pigment changes (intermediate AMD), in patients having intermediate
      AMD eyes with neovascular fellow eyes (nAMD), and in healthy subjects using three
      dimensional (3D) 1060-nm optical coherence tomography (OCT). METHODS:
      Automatically generated choroidal thickness (ChT), retinal thickness, and
      Sattler's and Haller's layer thickness maps were statistically analyzed in 67
      subjects consisting of intermediate AMD (n = 21), intermediate AMD (n = 22) with
      fellow nAMD eyes (n = 22), and healthy eyes (n = 24) with no age and axial eye
      length difference between groups of eyes (P > 0.05, ANOVA). Eyes were imaged by a
      prototype high-speed (60,000 A-scans/s) spectral-domain 3D 1060-nm OCT over a 36
      degrees  * 36 degrees  field of view. RESULTS: The mean +/- SD (MUm) subfoveal
      ChT for healthy subjects and for bilateral intermediate AMD, unilateral
      intermediate AMD, and their nAMD fellow eyes was 259 +/- 95 and 222 +/- 98, 149
      +/- 60, and 171 +/- 78, respectively. Choroidal thickness maps demonstrated
      significant submacular thinning in unilateral intermediate AMD in comparison to
      healthy and bilateral intermediate AMD eyes (P < 0.001, ANOVA, post hoc P < 0.001
      and P < 0.05, respectively). Sattler's and Haller's layers were thinnest in
      intermediate AMDs that presented with nAMD fellow eyes (Kruskal-Wallis test P <
      0.01). For the choroid and its sublayers, there was no difference between the
      intermediate AMD eyes and their fellow nAMD eyes (paired testing, P < 0.05).
      CONCLUSIONS: The 3D 1060-nm OCT choroidal imaging visualized significant changes
      in choroidal, Sattler's, and Haller's layer thickness in relation to the
      progression of AMD. This may be important for understanding the choroidopathy in
      the pathophysiology of AMD.

PMID- 25052998
TI  - Age-associated changes in the retinal nerve fiber layer and optic nerve head.
AB  - PURPOSE: Optical coherence tomography (OCT) measures of the retinal nerve fiber
      layer (RNFL) thickness and neuroretinal rim (NRR) parameters are often used as a
      surrogate for retinal ganglion cell content. The purpose of this study was to
      investigate the relationship between these morphological measures and the aging
      effects on these structures. METHODS: One hundred thirteen healthy individuals,
      aged 19 to 76 years, with no prior history of retinal of optic nerve head
      pathology were recruited. A circumpapillary and radial OCT scan centered on the
      optic nerve head (ONH) was used for data analysis. Transverse scaling was
      calculated for each subject using measures from optical biometry. Custom
      algorithms were used for morphological analysis of the ONH NRR and RNFL that
      included quantification of major retinal vascular contribution. RESULTS: There
      was a significant age-related loss of RNFL thickness (-0.23 MUm/y, R(2) = 0.24, P
      < 0.01), major retinal vascular contribution (-0.03 MUm/y, R(2) = 0.07, P = 0.01,
      neural rim volume (NRV, -0.004 mm(3)/y, R(2) = 0.15, P < 0.01), and minimum rim
      width (MRW, -1.77 MUm/y, R(2) = 0.23, P < 0.01) before, and after, incorporating
      the Bruch's membrane opening size (sMRW, -1.86 MUm/y, R(2) = 0.22, P < 0.01).
      When normalized, the rates of change for ONH NRR parameters (NRV, 0.69%/y and
      sMRW, 0.50%/y) exceeded that of RNFL thickness (0.19%/y, P < 0.01). CONCLUSIONS:
      Although both RNFL and ONH NRR parameters contain axons of retinal ganglion
      cells, there are differences in age-related changes in these measures that should
      be considered in clinical application.

PMID- 25052999
TI  - Characterization of Escherichia coli virulence genes, pathotypes and antibiotic
      resistance properties in diarrheic calves in Iran.
AB  - BACKGROUND: Calf diarrhea is a major economic concern in bovine industry all
      around the world. This study was carried out in order to investigate distribution
      of virulence genes, pathotypes, serogroups and antibiotic resistance properties
      of Escherichia coli isolated from diarrheic calves. RESULTS: Totally, 76.45% of
      824 diarrheic fecal samples collected from Isfahan, Chaharmahal, Fars and
      Khuzestan provinces, Iran were positive for E. coli and all of them were also
      positive for cnf2, hlyA, cdtIII, f17c, lt, st, stx1, eae, ehly, stx2 and cnf1
      virulence genes. Chaharmahal had the highest prevalence of STEC (84.61%), while
      Isfahan had the lowest (71.95%). E. coli serogroups had the highest frequency in
      1-7 days old calves and winter season. Distribution of ETEC, EHEC, AEEC and NTEC
      pathotypes among E. coli isolates were 28.41%, 5.07%, 29.52% and 3.49%,
      respectively. Statistical analyses were significant for presence of bacteria
      between various seasons and ages. All isolates had the high resistance to
      penicillin (100%), streptomycin (98.25%) and tetracycline (98.09%) antibiotics.
      The most commonly detected resistance genes were aadA1, sul1, aac[3]-IV, CITM,
      and dfrA1. The most prevalent serogroup among STEC was O26. CONCLUSIONS: Our
      findings should raise awareness about antibiotic resistance in diarrheic calves
      in Iran. Clinicians should exercise caution when prescribing antibiotics.

PMID- 25053000
TI  - Imprint of monsoonal patterns on the fish assemblage in coastal waters of south
      east India: a case study.
AB  - The composition, species richness and diversity of a coastal fish assemblage from
      the Kalpakkam coast of south-east India are described along with temporal
      distribution patterns related to seasonal fluctuations in dissolved oxygen,
      salinity, pH, chlorophyll-a, phytoplankton and zooplankton species richness and
      density. A total of 244 fish species belonging to 21 orders, 87 families and 163
      genera were recorded. The fish assemblage was dominated by reef-associated
      species, followed by demersal species. The majority of the species (63%) are
      widely distributed in the western Indo-Pacific as well as in the central Indo
      Pacific. Jaccard's coefficient analysis showed three distinct seasonal patterns
      of fish occurrence: pre-monsoon (PrM), monsoon (M) and post-monsoon (PoM). The
      maximum number of species was during the PrM period, followed by the PoM and M
      periods. Species occurrence analysis showed Sardinella longiceps to be dominant
      during PrM and M periods, Leiognathus dussumieri during the M period and Secutor
      insidiator and Secutor ruconius during the M and PoM periods. Canonical
      correspondence analysis indicated that salinity and rainfall were the two most
      influential environmental factors strongly correlated with temporal variation in
      the fish assemblage. The physico-chemical conditions, in combination with factors
      such as greater food availability and shelter, might control the seasonal local
      distribution of the ichthyofauna in these Indian coastal waters. 

PMID- 25053002
TI  - Pregnane-type steroidal glycosides from Gymnema griffithii Craib.
AB  - Eight pregnane-type steroidal glycosides substituted with ortho-acetate groups
      were isolated from the methanolic extract of the pericarp of Gymnema griffithii
      fruits, and named gymnemogriffithosides A-H. Their structures were determined by
      spectroscopic analysis (one and two dimensional nuclear magnetic resonance, high
      resolution electrospray ionization mass spectrometry and attenuated total
      reflectance-Fourier transformed infrared spectroscopy), while the absolute
      structure of the steroidal skeleton of one of these was additionally determined
      using Mosher's method. All compounds were evaluated for their in vitro (i)
      cytotoxic effects against five human tumor cell lines (BT 474, Chago, Hep-G2,
      KATO-III and SW620) and (ii) alpha-glucosidase inhibitory activity. 

PMID- 25053001
TI  - Whole-exome sequencing identifies a de novo TUBA1A mutation in a patient with
      sporadic malformations of cortical development: a case report.
AB  - BACKGROUND: Owing to the number of genetic mutations that contribute to
      malformations of cortical development, identification of causative mutations in
      candidate genes is challenging. To overcome these challenges, we performed whole
      exome sequencing in this study. CASE PRESENTATION: A Japanese patient presented
      with microcephaly and severe developmental delay. Brain magnetic resonance
      imaging showed the presence of colpocephaly associated with lateral ventricle
      dilatation and the presence of a simplified gyral pattern. Hypoplasia of the
      corpus callosum and cerebellar vermis were also noted. Because Sanger sequencing
      is expensive, laborious, and time-consuming, whole-exome sequencing was performed
      and a de novo missense mutation in TUBA1A (E27Q) was identified. CONCLUSION: The
      novel mutation identified in this study was located in the genetic region that
      encodes the N-terminal domain of TUBA1A, a region of TUBA1A with few reported
      mutations. Retrospective assessment of the clinical and radiological features of
      this patient-i.e., microcephaly, lissencephaly (pachygyria) with cerebellar
      hypoplasia, and corpus callosum hypoplasia-indicated that the TUBA1A mutation did
      not lead to any contradictions. Because rapid and comprehensive mutation analysis
      by whole-exome sequencing is time- and cost-effective, it might be useful for
      genetic counseling of patients with sporadic malformations of cortical
      development.

PMID- 25053003
TI  - Analyses of flooding tolerance of soybean varieties at emergence and varietal
      differences in their proteomes.
AB  - Flooding of fields due to heavy and/or continuous rainfall influences soybean
      production. To identify soybean varieties with flooding tolerance at the seedling
      emergence stage, 128 soybean varieties were evaluated using a flooding tolerance
      index, which is based on plant survival rates, the lack of apparent damage and
      lateral root development, and post-flooding radicle elongation rate. The soybean
      varieties were ranked according to their flooding tolerance index, and it was
      found that the tolerance levels of soybean varieties exhibit a continuum of
      differences between varieties. Subsequently, tolerant, moderately tolerant and
      sensitive varieties were selected and subjected to comparative proteomic analysis
      to clarify the tolerance mechanism. Proteomic analysis of the radicles, combined
      with correlation analysis, showed that the ratios of RNA binding/processing
      related proteins and flooding stress indicator proteins were significantly
      correlated with flooding tolerance index. The RNA binding/processing related
      proteins were positively correlated in untreated soybeans, whereas flooding
      stress indicator proteins were negatively correlated in flooded soybeans. These
      results suggest that flooding tolerance is regulated by mechanisms through
      multiple factors and is associated with abundance levels of the identified
      proteins.

PMID- 25053004
TI  - Time to retire the theory of planned behaviour.

PMID- 25053005
TI  - Planning for, implementing and assessing the impact of health promotion and
      behaviour change interventions: a way forward for health psychologists.
AB  - Researchers in the field of health psychology have increasingly been involved in
      translating a body of knowledge about psychological factors associated with
      health-relevant behaviours, into the development and evaluation of interventions
      that seek to apply that knowledge. In this paper we argue that a changing
      economic and political climate, and the strong behavioural contribution to
      disease morbidity and mortality in developed nations, requires health
      psychologists to plan more rigorously for, and communicate more effectively,
      about how health promotion, social cognition and behaviour change interventions
      will have impact and be increasingly embedded into health services or health
      promotion activity. We explain academic and wider socio-economic uses of 'impact'
      in health services research. We describe the relationship between impact and
      dissemination, and impact as distinct from, but often used interchangeably with
      the terms 'implementation', 'knowledge transfer' and 'knowledge translation'
      (KT). The evidence for establishing impact is emergent. We therefore draw on a
      number of impact planning and KT frameworks, with reference to two self-
      management interventions, to describe a framework that we hope will support
      health psychologists in embedding impact planning and execution in research. We
      illustrate this further in an on-line annexe with reference to one of our own
      interventions, Mums-and-MS (see Supplemental Material). 

PMID- 25053006
TI  - Facilitating progress in health behaviour theory development and modification:
      the reasoned action approach as a case study.
AB  - This paper explores the question: what are barriers to health behaviour theory
      development and modification, and what potential solutions can be proposed? Using
      the reasoned action approach (RAA) as a case study, four areas of theory
      development were examined: (1) the theoretical domain of a theory; (2) tension
      between generalisability and utility, (3) criteria for adding/removing variables
      in a theory, and (4) organisational tracking of theoretical developments and
      formal changes to theory. Based on a discussion of these four issues,
      recommendations for theory development are presented, including: (1) the
      theoretical domain for theories such as RAA should be clarified; (2) when there
      is tension between generalisability and utility, utility should be given
      preference given the applied nature of the health behaviour field; (3) variables
      should be formally removed/amended/added to a theory based on their performance
      across multiple studies and (4) organisations and researchers with a stake in
      particular health areas may be best suited for tracking the literature on
      behaviour-specific theories and making refinements to theory, based on a
      consensus approach. Overall, enhancing research in this area can provide
      important insights for more accurately understanding health behaviours and thus
      producing work that leads to more effective health behaviour change
      interventions. 

PMID- 25053007
TI  - Life and death of health behaviour theories.

PMID- 25053008
TI  - Improving translational research in building theory: a commentary on Head and
      Noar.

PMID- 25053009
TI  - Mind the gap: bringing our theories in line with the empirical data - a response
      to commentaries.

PMID- 25053010
TI  - The impact of familism on physical and mental health among Hispanics in the
      United States.
AB  - The rapidly expanding number of Hispanics living in USA has increased the need
      for their inclusion in research on physical and mental health. Current studies
      that have explored health outcomes among Hispanics have often noted an
      'epidemiological paradox', in which there is a discrepancy between their minority
      status and positive health outcomes when compared with other racial/ethnic
      groups. Certain socio-cultural variables, in particular the value placed on
      family, have been largely implicated in these findings. This review will provide
      a summary of the literature exploring familism within the structure of the
      Hispanic family and its potential impact on health. We will focus on research
      exploring the plausible impact that family and familism values may have on the
      physical health (particularly within the HIV, diabetes, and breast cancer
      literature) and also on health behaviours of Hispanics, as well as its effect on
      mental health (particularly related to acculturative stress and caregiver
      stress). Throughout the review, we highlight some of the potential mechanisms by
      which familism may impact on the health status of Hispanics. We conclude the
      review by noting some of the clinical and ethical implications of this research,
      and by offering suggestions for future work in this area. 

PMID- 25053013
TI  - Automatic classification of left ventricular wall segments in small animal
      ultrasound imaging.
AB  - Multiple statistics show that heart diseases are one of the main causes of
      mortality in our highly developed societies today. These diseases lead to a
      change of the physiology of the heart, which gives useful information about
      characteristic and severity of the defect. A fast and reliable diagnosis is the
      base for successful therapy. As a first step towards recognition of such heart
      remodeling processes, this work proposes a fully automatic processing pipeline
      for regional classification of the left ventricular wall in ultrasound images of
      small animals. The pipeline is based on state-of-the-art methods from computer
      vision and pattern classification. The myocardial wall is segmented and its
      motion is estimated. A feature extraction using the segmented data is realized to
      automatically classify the image regions into normal and abnormal myocardial
      tissue. The performance of the proposed pipeline is evaluated and a comparison of
      common classification algorithms on ultrasound data of living mice before and
      after artificially induced myocardial infarction is given. It is shown that the
      results of this work, reaching a maximum accuracy of 91.46%, are an encouraging
      base for further investigation. 

PMID- 25053011
TI  - Runx2-Smad signaling impacts the progression of tumor-induced bone disease.
AB  - Runx2, a master regulator of osteogenesis, is abnormally expressed in advanced
      prostate cancer. Here, we addressed Runx2 contribution to formation of prostate
      cancer-related osteolytic and osteoblastic bone lesions by mediating TGFbeta/BMP
      signaling through direct interaction with Smads. Further, we examined involvement
      of the Runx2-Smad complex in mediating tumor growth and distal metastasis. To
      identify Runx2-Smad-specific mechanisms of prostate tumor activity in bone, we
      generated PC3 prostate cancer cell lines expressing Runx2-WT or one of two mutant
      proteins (Runx2-HTY and Runx2-DeltaC) that each disrupt the Runx2-Smad
      interaction, either directly through a point mutation or by deletion of the
      functional C-terminus, respectively. Intratibial tumors generated from these
      cells revealed that Runx2-WT-expressing cells resulted in predominantly
      osteolytic disease, whereas cells expressing mutant proteins exhibited tumors
      with mixed osteolytic/osteoblastic lesions. Extent of bone loss and woven bone
      formation was assessed by radiography and micro-computed tomography.
      Bioluminescent imaging showed the presence of labeled prostate cancer cells in
      the lung at the latest time point examined, with Runx2-WT group exhibiting
      increased incidence of tumor cells in lung. Notably, disruption of the Runx2-Smad
      interaction significantly reduced incidence and size of lung tumors. Altered
      expression of Runx2 target genes involved in invasion, growth, adhesion and
      metastasis supported our findings. Thus, our studies demonstrate that Runx2 in
      prostate cancer cells plays a significant role in intratibial prostate cancer
      related tumor growth and bone loss through mechanisms mediated by the Runx2-Smad
      signaling pathway. This work expands upon the potential importance of Runx2 as a
      therapeutic target in cancer. 

PMID- 25053012
TI  - Physical activity and physical self-concept in youth: systematic review and meta
      analysis.
AB  - BACKGROUND: Evidence suggests that physical self-concept is associated with
      physical activity in children and adolescents, but no systematic review of this
      literature has been conducted. OBJECTIVE: The primary aim of this systematic
      review and meta-analysis was to determine the strength of associations between
      physical activity and physical self-concept (general and sub-domains) in children
      and adolescents. The secondary aim was to examine potential moderators of the
      association between physical activity and physical self-concept. METHODS: A
      systematic search of six electronic databases (MEDLINE, CINAHL, SPORTDiscus,
      ERIC, Web of Science and Scopus) with no date restrictions was conducted. Random
      effects meta-analyses with correction for measurement were employed. The
      associations between physical activity and general physical self-concept and sub
      domains were explored. A risk of bias assessment was conducted by two reviewers.
      RESULTS: The search identified 64 studies to be included in the meta-analysis.
      Thirty-three studies addressed multiple outcomes of general physical self
      concept: 28 studies examined general physical self-concept, 59 examined perceived
      competence, 25 examined perceived fitness, and 55 examined perceived appearance.
      Perceived competence was most strongly associated with physical activity (r =
      0.30, 95% CI 0.24-0.35, p < 0.001), followed by perceived fitness (r = 0.26, 95%
      CI 0.20-0.32, p < 0.001), general physical self-concept (r = 0.25, 95% CI 0.16
      0.34, p < 0.001) and perceived physical appearance (r = 0.12, 95% CI 0.08-0.16, p
      < 0.001). Sex was a significant moderator for general physical self-concept (p <
      0.05), and age was a significant moderator for perceived appearance (p <= 0.01)
      and perceived competence (p < 0.05). No significant moderators were found for
      perceived fitness. CONCLUSION: Overall, a significant association has been
      consistently demonstrated between physical activity and physical self-concept and
      its various sub-domains in children and adolescents. Age and sex are key
      moderators of the association between physical activity and physical self
      concept.

PMID- 25053014
TI  - Midterm outcomes of protection for upper urinary tract function by augmentation
      enterocystoplasty in patients with neurogenic bladder.
AB  - PURPOSE: To evaluate the midterm outcomes of protection for upper urinary tract
      (UUT) function by augmentation enterocystoplasty (AE) using a grading system for
      upper urinary tract dilation (UUTD) and a descriptive system for all urinary
      tract dysfunction (AUTD) in patients with neurogenic bladder. METHODS: We
      retrospectively reviewed 120 cases of AE from our database, which was collected
      between 2005 and 2013. UUTD grading system was developed by magnetic resonance
      urography (MRU), and AUTD system was described by video-urodynamics, MRU, isotope
      renography, etc. UUT function was evaluated by these systems before operation,
      and at 6, 12, 24 and 36 months postoperatively. The indication, midterm outcomes
      and complications were evaluated. RESULTS: All patients had significant
      improvement for urodynamic parameters at 6 months postoperatively. Comparing the
      grades of UUTD and vesicoureteral reflux (VUR) before and after operation, the
      median grade of 95 UUTD ureters decreased from 3 to 0, and the percentage of 0
      grade UUTD increased from 0 to 90.9 % at 36 months. The median grade of 96 VUR
      ureters decreased from 3 to 0, and the percentage of 0 grade VUR increased from 0
      to 98.6 % at 36 months. The glomerular filtration rate of kidneys and serum
      creatinine level of patients had an increasing improvement after surgery.
      CONCLUSIONS: The midterm follow-up using UUTD and AUTD systems indicates that AE
      is effective and safe for UUT protection. The patients with moderate and severe
      UUT deteriorations and renal function impairment resulting from VUR and UUTD have
      undergone the increasing improvement.

PMID- 25053015
TI  - Intimate partner violence against Spanish pregnant women: application of two
      screening instruments to assess prevalence and associated factors.
AB  - OBJECTIVE: To investigate the prevalence of intimate partner violence in Spanish
      women during the 12 months prior to delivery and to identify associated risk
      factors using two screening instruments. DESIGN: A population-based study.
      SETTING: Fifteen public hospitals in southern Spain. POPULATION: A total of 779
      women admitted to the hospital obstetrics department. METHODS: Intimate partner
      violence was diagnosed with the Abuse Assessment Screen and Index of Spouse Abuse
      screening instruments. MAIN OUTCOME MEASURES: Prevalence and associated risk
      factors of intimate partner violence during pregnancy. RESULTS: According to the
      Abuse Assessment Screen, intimate partner violence during the pre-delivery year
      was experienced by 7.7% of the women, emotional abuse by 4.8%, and physical abuse
      by 1.7%. According to the Index of Spouse Abuse, non-physical intimate partner
      violence during this period was reported by 21.0% of the women and physical
      intimate partner violence by 3.6%. After adjusting for socio-demographic
      characteristics, multivariate regression models showed that an uncommitted
      relationship and absence of kin support were significantly associated with an
      increased intimate partner violence risk during the pre-delivery year. Employment
      was a significant protective factor against any of the three forms of intimate
      partner violence (Abuse Assessment Screen) and physical intimate partner violence
      (Index of Spouse Abuse) during this period. CONCLUSIONS: A high proportion of
      women in Spain experience intimate partner violence during or just before
      pregnancy. Pregnant women in an uncommitted relationship or without kin support
      were at greater risk of intimate partner violence. Screening instruments for
      intimate partner violence during pregnancy should be evaluated in different
      cultural contexts.

PMID- 25053016
TI  - Expression of the SERPING1 gene is not regulated by promoter hypermethylation in
      peripheral blood mononuclear cells from patients with hereditary angioedema due
      to C1-inhibitor deficiency.
AB  - SERPING1 mutations causing Hereditary Angioedema type I (HAE-I) due to C1
      Inhibitor (C1-INH) deficiency display a dominant-negative effect usually
      resulting in protein levels far below the expected 50%. To further investigate
      mechanisms for its reduced expression, we analyzed the promoter DNA methylation
      status of SERPING1 and its influence on C1-INH expression. Global epigenetic
      reactivation correlated with C1-INH mRNA synthesis and protein secretion in Huh7
      hepatoma cells. However, PBMCs extracted from controls, HAE-I and HAE-II patients
      presented identical methylation status of the SERPING1 promoter when analyzed by
      bisulphite sequencing; the proximal CpG island (exon 2) is constitutively
      unmethylated, while the most distant one (5.7Kb upstream the transcriptional
      start site) is fully methylated. These results correlate with the methylation
      profile observed in Huh7 cells and indicate that there is not a direct epigenetic
      regulation of C1-INH expression in PBMCs specific for each HAE type. Other
      indirect modes of epigenetic regulation cannot be excluded. 

PMID- 25053017
TI  - Successful treatment of molluscum contagiosum with intralesional immunotherapy by
      measles, mumps, and rubella vaccine: a report of two cases.
AB  - Molluscum contagiosum (MC) is a common viral infection of the skin and mucous
      membrane that often affects young children. Generally, physical removal by
      surgical curettage is commonly used for the treatment of MC, but the pain during
      the treatment is a major problem. Thus immunotherapy using various antigens has
      been introduced recently. Here we present two cases of MC that improved with
      measles, mumps, and rubella (MMR) vaccine intralesional injection. On the ground
      of our knowledge, they were the first cases of successful MMR intralesional
      injection in this disease entity.

PMID- 25053018
TI  - AtMyb7, a subgroup 4 R2R3 Myb, negatively regulates ABA-induced inhibition of
      seed germination by blocking the expression of the bZIP transcription factor
      ABI5.
AB  - Various Myb proteins have been shown to play crucial roles in plants, including
      primary and secondary metabolism, determination of cell fate and identity,
      regulation of development and involvement in responses to biotic and abiotic
      stresses. The 126 R2R3 Myb proteins (with two Myb repeats) have been found in
      Arabidopsis; however, the functions of most of these proteins remain to be fully
      elucidated. In the present study, we characterized the function of AtMyb7 using
      molecular biological and genetic analyses. We used qRT-PCR to determine the
      levels of stress-response gene transcripts in wild-type and atmyb7 plants. We
      showed that Arabidopsis AtMyb7 plays a critical role in seed germination. Under
      abscisic acid (ABA) and high-salt stress conditions, atmyb7 plants showed a lower
      germination rate than did wild-type plants. Furthermore, AtMyb7 promoter:GUS
      seeds exhibited different expression patterns in response to variations in the
      seed imbibition period. AtMyb7 negatively controls the expression of the gene
      encoding bZIP transcription factor, ABI5, which is a key transcription factor in
      ABA signalling and serves as a crucial regulator of germination inhibition in
      Arabidopsis. 

PMID- 25053019
TI  - Reciprocal Longitudinal Associations Between Adolescent Twin Gambling and
      Delinquency.
AB  - This study examined sibling influence over gambling involvement and delinquency
      in a sample of 628 twins (151 male dyads, 163 female dyads). Self-reports of
      gambling involvement and delinquency were collected for each twin at ages 13, 14
      and 15 years. Results revealed evidence of between-twin influence. Higher levels
      of an adolescent's delinquency predicted an increase in his or her co-twin's
      delinquency from age 13 to age 14 and from age 14 to age 15. In contrast,
      gambling behavior was unaffected by the co-twin's gambling involvement. Within
      twins, higher initial levels of delinquency predicted a subsequent increase in
      gambling behavior from age 13 to age 14 and again from age 14 to age 15, and
      higher initial levels of gambling involvement predicted an increase in
      delinquency from age 14 to age 15. Between and within siblings effects are
      discussed in light of the scant literature on (a) sibling influence on gambling,
      and (b) the links between gambling and delinquency.

PMID- 25053020
TI  - Two alternative multiplex PCRs for the identification of the seven species of
      anglerfish (Lophius spp.) using an end-point or a melting curve analysis real
      time protocol.
AB  - Anglerfish (Lophius spp.) is consumed worldwide and is an important economic
      resource though its seven species are often fraudulently interchanged due to
      their different commercial value, especially when sold in the form of fillets or
      pieces. Molecular analysis is the only possible mean to verify traceability and
      counteract fraud. We developed two multiplex PCRs, one end-point and one real
      time with melting curve post-amplification analysis, which can even be run with
      the simplest two-channel thermocyclers. The two methods were tested on seventy
      five reference samples. Their specificity was checked in twenty more species of
      those most commonly available on the market and in other species of the Lophiidae
      family. Both methods, the choice of which depends on the equipment and budget of
      the lab, provide a rapid and easy-to-read response, improving both the simplicity
      and cost-effectiveness of existing methods for identifying Lophius species. 

PMID- 25053021
TI  - New technique to isolate anthocyanins from Delaware grapes by forming an
      aluminium complex using a Discovery DPA-6S.
AB  - An aluminium complex of crude Delaware grape anthocyanins, bearing an ortho
      dihydroxyl group on the B ring and/or a p-coumaroyl group as an ester with
      flavocommelin, was formed and isolated by ethanol precipitation. Using a
      Discovery DPA-6S short column, selected anthocyanins were isolated to give
      cyanidin 3-glucoside (Cy3G, 48.2% yield with 95.2% purity) and cyanidin 3-(6-O-p
      coumaroylglucoside) (Cy3-pC.G, 44.9% yield with 91.4% purity) from natural
      Delaware grape skin extracts without ODS-HPLC column chromatography. DPPH radical
      scavenging activity of the complex pigment was 3.4 +/- 0.10 MUmol TE/mg.
      Moreover, isolated pure anthocyanins from the complex pigment showed
      significantly higher DPPH radical scavenging activity [4.5 +/- 0.08 MUmol TE/mg
      (Cy3G) and 4.5 +/- 0.04 MUmol TE/mg (Cy3-pC.G), (p<0.05)].

PMID- 25053022
TI  - Antioxidant compounds, antioxidant activity and phenolic content in peel from
      three tropical fruits from Yucatan, Mexico.
AB  - The aim of this study was to determine the antioxidant compounds, antioxidant
      activity and content of individual phenolic compounds of freeze-dried peel from
      three tropical fruits grown in Yucatan, Mexico: purple star apple (Chrysophyllum
      cainito L.), yellow cashew and red cashew (Anacardium occidentale). The freeze
      dried peels were good source of antioxidant compounds. ABTS and DPPH values in
      the peel from each fruit were 3050.95-3322.31 MUM Trolox/100g dry weight (DW) or
      890.19-970.01 mg of vitamin C/100 g DW, and 1579.04-1680.90 MUM Trolox/100 g DW
      or 340.18-362.18 mg of vitamin C/100 g DW, respectively. Six phenolic compounds
      were identified in the peel from the tropical fruits studied: ferulic, caffeic,
      sinapic, gallic, ellagic and myricetin. This study demonstrated that freeze-dried
      peels from purple star apple, yellow cashew and red cashew, could serve as
      potential sources of antioxidants for use in food and pharmaceutical industries.

PMID- 25053024
TI  - Automatic determination of polyphenols in wines using laccase and terbium oxide
      nanoparticles.
AB  - The analytical usefulness of the combined use of laccase, terbium oxide
      nanoparticles (Tb4O7NPs) and 8-hydroxypyrene-3-sulphonate trisodium (HPTS) for
      the determination of polyphenol compounds in wine samples is described. The
      system is based on the temporal inhibition by polyphenols on the decrease of the
      HPTS fluorescence in the presence of laccase and on the activating effect of
      Tb4O7NPs, which increase the reaction rate of the system, shortening analysis
      times. The method has been developed in a microplate format using an automatic
      reader, reaching a sample throughput of 35 samples h(-1). The dynamic range of
      the calibration graph is 0.5-12 MUM gallic acid, which was chosen as model
      analyte, and the detection limit is 0.14 MUM. Precision data, expressed as
      relative standard deviation, ranged between 2.5% and 6.3%. The method was applied
      to the analysis of several wine samples, obtaining recovery values in the range
      of 80.0-108.3%.

PMID- 25053023
TI  - Simultaneous determination of zearalenone and its derivatives in edible vegetable
      oil by gel permeation chromatography and gas chromatography-triple quadrupole
      mass spectrometry.
AB  - A sensitive gas chromatographic-triple quadrupole mass spectrometric (GC-QqQ MS)
      analytical method, for the determination of zearalenone and its five derivatives
      in edible vegetable oil, was developed. After the vegetable oil samples were
      prepared using gel permeation chromatography, the eluent was collected,
      evaporated and dried with nitrogen gas. The residue was silylated with N,O-bis
      trimethylsilyltrifluoroacetamide, containing 1% trimethylchlorosilane. GC-QqQ MS
      was performed in the reaction-monitoring mode to confirm and quantify mycotoxins
      in vegetable oil. The limits of quantitation were 0.03-0.2 MUg kg(-1) for the six
      mycotoxins. The average recoveries, measured at 2, 20 and 200 MUg kg(-1), were in
      the range 80.3-96.5%. Zearalenone was detected in the range 5.2-184.6 MUg kg(-1)
      in nine maize oils and at 40.7 MUg kg(-1) in a rapeseed oil from the local
      market.

PMID- 25053025
TI  - The efficacy of kaolin particle film on oil quality indices of olive trees (Olea
      europaea L.) cv 'Zard' grown under warm and semi-arid region of Iran.
AB  - Kaolin particle film (0%, 3% and 6%; w/v), as an antitranspirant treatment, was
      applied to mature 'Zard' olive trees (Olea europaea L.). Olive oil was extracted
      from harvested fruit and fatty acid composition and other oil quality indices of
      the fruit assessed over crop seasons. Kaolin increased chlorophyll and carotenoid
      contents, but decreased peroxide and iodine values, and UV absorbance extinction
      coefficients, of the oil. The highest palmitic acid was observed in the oil
      obtained from untreated trees (17%). Kaolin increased oleic acid up to 65% and
      64% in the first and second crop seasons, respectively, but decreased linoleic
      and linolenic acid contents. Monounsaturated acids (65%) and oleic acid/linoleic
      acid ratios (4) were higher in oil obtained from kaolin treated than untreated
      trees. Therefore it can be expected that extracted olive oil from kaolin treated
      trees has a higher oxidative stability and shelf life than untreated trees. 

PMID- 25053026
TI  - Strategy to identify and quantify polysaccharide gums in gelled food
      concentrates.
AB  - A strategy for the unambiguous identification and selective quantification of
      xanthan gum and locust bean gum (LBG) in gelled food concentrates is presented.
      DNA detection by polymerase chain reaction (PCR) showed to be a fast, sensitive,
      and selective method that can be used as a first screening tool in intact gelled
      food concentrates. An efficient isolation procedure is described removing
      components that may interfere with subsequent analyses. NMR spectroscopy enabled
      the direct identification of xanthan gum and the discrimination between different
      galactomannans in the isolated polysaccharide fraction. An enzymatic
      fingerprinting method using endo-beta-mannanase, in addition to being used to
      differentiate between galactomannans, was developed into a selective,
      quantitative method for LBG, whereas monosaccharide analysis was used to quantify
      xanthan gum. Recoveries for xanthan gum and LBG were 87% and 70%, respectively,
      with in-between day relative standard deviations below 20% for xanthan gum and
      below 10% for LBG. 

PMID- 25053027
TI  - A novel copigment of quercetagetin for stabilization of grape skin anthocyanins.
AB  - The thermal and light stability of grape skin anthocyanins combined with
      quercetagetin was investigated at designed pH values of 3, 4 and 5. The molar
      ratios of anthocyanins to quercetagetin were 1:10, 1:20 and 1:40 for thermally
      treatment at 70  degrees C, 80  degrees C and 90  degrees C, respectively, and
      the ratios were tested at 5:1, 1:1, 1:5 and 1:10 in the light exposure
      experiments. The degradation reaction of anthocyanins in the presence of
      quercetagetin followed the first-order kinetic model. The half-life (t1/2) of
      anthocyanins was extended significantly with the increase of quercetagetin
      concentration (p<0.05). The total colour difference values (DeltaE(*)) for the
      anthocyanin solutions with quercetagetin were smaller than those without
      copigment under the same experimental conditions (pH and light exposure time).
      Compared with epigallocatechin gallate (EGCG), tea polyphenols (TP), myricitrin
      and rutin, quercetagetin was the most effective copigment to stabilize grape skin
      anthocyanins.

PMID- 25053028
TI  - Pre-fermentation addition of grape tannin increases the varietal thiols content
      in wine.
AB  - The recent finding that grape tannin may contain significant amount of S
      glutathionylated (GSH-3MH) and S-cysteinylated (Cys-3MH) precursors of the
      varietal thiols 3-mercapto-1-hexanol and 3-mercaptohexyl acetate, characteristic
      of Sauvignon blanc wines, offers new opportunities for enhancing the tropical
      aroma in fermented beverages. In this study this new hypothesis was investigated:
      Muller Thurgau (17 samples) and Sauvignon blanc (15 samples) grapes were
      fermented with and without addition of a selected grape tannin. As expected, the
      tannin-added juices were higher in precursors, and they produced wines with
      increased free thiols. Preliminary informal sensory tests confirmed that in
      particular the Sauvignon wines produced with the tannin addition were often
      richer with increased "fruity/green" notes than the corresponding reference
      wines. This outcome confirms that grape tannin addition prior to fermentation can
      fortify the level of these compounds. 

PMID- 25053029
TI  - Probing the conformational changes of ovalbumin after glycation using HDX-MS.
AB  - The conformational changes of the glycated ovalbumin were studied by
      hydrogen/deuterium exchange coupled with high resolution mass spectrometry
      technique (HDX-MS). After incubation with glucose at 50  degrees C for 6 h, 9
      glycated peptides were detected and the corresponding glycation sites were
      identified. The glycation extent of each peptide was relatively high, almost over
      0.5 in all peptides. A detailed peptide mapping revealed that most of the
      peptides, including the glycated and non-glycated were protected. The glycation
      sites not only influence the local region but also the distant area. The enhanced
      hydrogen protection after glycation suggests that the protein adopts a more
      stable conformation.

PMID- 25053030
TI  - Effects of industrial canning on the proximate composition, bioactive compounds
      contents and nutritional profile of two Spanish common dry beans (Phaseolus
      vulgaris L.).
AB  - This study investigated the changes produced by canning in the proximate
      composition and in the bioactive constituents of two "ready to eat" Spanish
      beans. The foremost difference in the raw beans corresponded to the lectin: a
      higher content was found in raw Curruquilla beans (16.50 mg 100 mg(-1)) compared
      with raw Almonga beans (0.6 mg 100 mg(-1)). In general, industrial canning
      significantly increased the protein (>7%) and dietary fibre (>5%) contents of
      both beans varieties. However, the minerals, total alpha-galactosides and
      inositol phosphates contents were reduced (>25%) in both canned seeds. The
      trypsin inhibitors content was almost abolished by canning, and no lectins were
      found in either of the canned samples. Canned Curruquilla showed a decrease (38%)
      of their antioxidant activity. These "ready to eat" beans exhibited adequate
      nutritive profiles according to the USDA dietary recommendations. Furthermore,
      they had bioactive components content that are suitable for establishing a
      healthy lifestyle.

PMID- 25053031
TI  - Migration and characterisation of nanosilver from food containers by AF4-ICP-MS.
AB  - In this work, silver migration from commercial food containers was evaluated
      according to European Regulation 10/2011. Several experimental parameters
      affected silver release: food simulant, temperature, exposition time and sampled
      bag area. Results demonstrated a significant silver nanoparticle (AgNP) migration
      into aqueous and acidic simulants. The amount of silver migrated increased with
      storage time and temperature although, in general, silver showed a low tendency
      to migrate into food simulants (17 ng/g). However, the food simulant did not seem
      to be a really outstanding variable for long term storage. AF(4)-ICP MS was used
      to confirm the presence of AgNPs in the simulants. The low limit of detection
      achieved (0.4 MUg L(-1)) allowed the identification of AgNPs and their size
      characterisation (40-60 nm). Finally, scanning electron microscopy/energy
      dispersive X-ray analysis suggested a possible transformation of the AgNPs
      detected in the extracts, due to association with other ligands, such as chlorine
      and sulphur, present in the original containers.

PMID- 25053033
TI  - Reverse micellar extraction of lectin from black turtle bean (Phaseolus
      vulgaris): optimisation of extraction conditions by response surface methodology.
AB  - Lectin from black turtle bean (Phaseolus vulgaris) was extracted and purified by
      reverse micellar extraction (RME) method. Response surface methodology (RSM) was
      used to optimise the processing parameters for both forward and backward
      extraction. Hemagglutinating activity analysis, SDS-PAGE, RP-HPLC and FTIR
      techniques were used to characterise the lectin. The optimum extraction
      conditions were determined as 77.59 mM NaCl, pH 5.65, AOT 127.44 mM sodium bis (2
      ethylhexyl) sulfosuccinate (AOT) for the forward extraction; and 592.97 mM KCl,
      pH 8.01 for the backward extraction. The yield was 63.21 +/- 2.35 mg protein/g
      bean meal with a purification factor of 8.81 +/- 0.17. The efficiency of RME was
      confirmed by SDS-PAGE and RP-HPLC, respectively. FTIR analysis indicated there
      were no significant changes in the secondary protein structure. Comparison with
      conventional chromatographic method confirmed that the RME method could be used
      for the purification of lectin from the crude extract.

PMID- 25053032
TI  - Effects of high hydrostatic pressure treatment on the enhancement of functional
      components of germinated rough rice (Oryza sativa L.).
AB  - This study was performed to evaluate the enhancement of functional components of
      germinated rough rice. Rough rice was germinated at 37  degrees C for 6 days, and
      subjected to a high hydrostatic pressure treatment (HPT) at 30 MPa for 24 h
      (HP24) and 48 h (HP48). Germinated rough rice without HPT (HP0), HP24, and HP48
      were analysed for their functional components. The highest gamma-aminobutyric
      acid, total arabinoxylan, and tricin 4'-O-(threo-beta-guaiacylglyceryl) ether
      contents were 121.21 mg/100g, 10.6%, and 85.82 MUg/g, respectively, after HP48
      for 2 days. gamma-Oryzanol contents increased from 23.19-36.20 mg/100g (at HP0)
      to 31.80-40.32 mg/100g (at HP48). The highest vitamin B (60.99 mg/100g) and E
      (4.07 mg/100g) contents were observed after HP24 for 5 and 2 days, respectively.
      These results suggest that a combination of HPT and germination efficiently
      enhances the functional characteristics of rough rice.

PMID- 25053034
TI  - Assessment of physicochemical and antioxidant characteristics of Quercus
      pyrenaica honeydew honeys.
AB  - Consumers are exhibiting increasing interest in honeydew honey, principally due
      to its functional properties. Some plants can be sources of honeydew honey, but
      in north-western Spain, this honey type only comes from Quercus pyrenaica. In the
      present study, the melissopalynological and physicochemical characteristics and
      the antioxidant properties of 32 honeydew honey samples are described. Q.
      pyrenaica honeydew honey was defined by its colour, high pH, phenols and
      flavonoids. Multivariate statistical techniques were used to analyse the
      influence of the production year on the honey's physicochemical parameters and
      polyphenol content. Differences among the honey samples were found, showing that
      weather affected the physicochemical composition of the honey samples. Optimal
      conditions for oak growth favoured the production of honeydew honey. 

PMID- 25053035
TI  - Physical, mechanical and antimicrobial properties of starch films incorporated
      with epsilon-poly-L-lysine.
AB  - Starch/epsilon-poly-L-lysine (epsilon-PL) composite films were prepared by
      combining 4% (w/v) gelatinized cornstarch and varying the level of epsilon-PL.
      The physical, mechanical and antimicrobial properties of these films were
      investigated. Fourier-transform infrared spectra (FT-IR) showed that the carbonyl
      group stretching vibration band of the epsilon-PL molecule shifted from 1646 cm(
      1) to 1673 cm(-1) in the composite films. Differential scanning calorimetry (DSC)
      results indicated that there were sharp endothermal peaks at 215-230  degrees C
      for the composite films. These results indicated that there was an intense
      interaction between the two components. The films incorporated with epsilon-PL
      showed a higher tensile strength (TS) and elongation-at-break (E) than those of
      the starch film alone. These composite films exhibited effective inhibition
      against Escherichia coli and Bacillus subtilis, films containing 2% (w/w) epsilon
      PL effectively suppressed the growth of the tested microbes (P<0.05). The
      starch/epsilon-PL films showed a low inhibitory effect on Aspergillus niger. This
      antimicrobial trend of the composite films was in agreement with the results of
      free epsilon-PL.

PMID- 25053036
TI  - Composition of pigments and colour changes in green table olives related to
      processing type.
AB  - Brownish colourations in Natural green table olives (non-treated with alkali)
      make this product less attractive to consumers than Spanish-style green table
      olives (treated with alkali), which develop a more appreciated bright golden
      yellow colour. These colour differences were studied in relation to changes in
      the composition of chlorophyll and carotenoid pigments, as well as polyphenolic
      compounds and polyphenol oxidase enzyme (PPO) activity. Natural green olives
      showed a different chlorophyll profile than Spanish-style. However, all the
      chlorophyll pigments formed in both processing types were Mg-free derivatives
      (mostly pheophytins) with similar colourations, ranging from grey to green
      brownish. In the carotenoid fraction no appreciable differences were found
      between both processing types. The fruit's brownish colour was mainly due to
      polymeric substances with a size of >1000 daltons and polyphenolic nature,
      resulting from an enzymatic oxidation by PPO of the o-diphenolic compounds
      present in the fresh fruits. 

PMID- 25053037
TI  - Nutritional composition and fatty acids profile in cocoa beans and chocolates
      with different geographical origin and processing conditions.
AB  - Nutritional composition and fatty acids (FA) profile were determined in cocoa and
      chocolates of different geographical origin and subject to different processing
      conditions. Cocoa butter was the major nutrient in cocoa beans and carbohydrates
      were the most important in chocolates. Cocoa composition and FA profile varied
      depending on geographical origin whilst in chocolates only carbohydrates and fat
      content varied significantly due to the effect of origin and no significant
      effect was observed for processing conditions. Both for cocoa and chocolates
      differences in FA profile were mainly explained as an effect of the geographical
      origin, and were not due to processing conditions in chocolate. For cocoa,
      differences in FA profile were found in C12:0, C14:0, C16:0, C16:1, C17:0, C17:1
      and C18:0 whilst for chocolates only differences were found in C16:0, C18:0,
      C18:1 and C18:2. For all samples, C16:0, C18:0, C18:1 and C18:2 were
      quantitatively the most important FA. Ecuadorian chocolate showed a healthier FA
      profile having higher amounts of unsaturated FA and lower amounts of saturated FA
      than Ghanaian chocolate. 

PMID- 25053038
TI  - Instrumental and sensory characterisation of Solaris white wines in Denmark.
AB  - This study aimed to investigate the volatile and non-volatile compositions as
      well as sensory properties of the most common monovarietal white wine (var.
      Solaris) in Denmark. Using dynamic headspace sampling (DHS) coupled to gas
      chromatography-mass spectrometry (GC-MS), 79 volatile compounds were identified.
      Among the major non-volatile components glycerol, sulphite, sugars and organic
      acids were analysed. A primary sensory difference was observed among wine
      samples, half of which were characterised by floral and fruity flavours
      (peach/apricot, Muscat, melon, banana and strawberry) while the remainder were
      described by less pleasant flavours, such as chemical, wood and rooibos/smoke.
      Partial least squares regression (PLS) showed that acetates and ethyl esters of
      straight-chain fatty acids were associated with floral and fruity odours while
      ethyl esters of branched-chain fatty acids were less associated with them. The
      study also suggested that differences in vintage were less characteristic than
      differences caused due to sulphite management by producers. 

PMID- 25053039
TI  - Chemical characterisation and in vitro assessment of the nutritive value of co
      products yield from the corn wet-milling process.
AB  - The chemical characteristics of co-products recovered during a laboratory-scale
      wet milling procedure as well as that of whole corn flour were characterised and
      their digestibility and fermentability value determined using a 2 steps in vitro
      digestibility and fermentation model of the pig digestive tract. Five co-products
      differing in their chemical composition were collected and analysed. These co
      products differed in their in vitro dry matter Digestibility and in their kinetic
      of fermentation. High coefficients of digestibility were observed for starchy
      samples, while low coefficients of digestibility were observed for samples rich
      in lignocellulosic components. Fermentation patterns of samples analysed were
      different as well as the profile of volatile fatty acids produced during the
      fermentation. The production of straight-chain fatty acids produced was
      significantly correlated with the proportion of starch in the sample, while
      branched-chain fatty acids were correlated to proteins concentration of samples. 

PMID- 25053040
TI  - Aqueous two phase system based on ionic liquid for isolation of quinine from
      human plasma sample.
AB  - Aqueous two phase system was applied for selective extraction of quinine from
      human plasma. Bi-phase was constructed from ionic liquid: butyl-methyl
      imidazolium chloride after addition kosmotropic salts K3PO4 or KH2PO4. Quinine
      was determined in plasma samples after drinking of tonic containing quinine.
      Determination was performed by HPLC on 5-MUm Zorbax SB-CN column and eluent
      containing 40% acetonitrile (v/v), 20 mM phosphate buffer at pH 3 and 40 mM NaPF6
      using external standard method. The spectrophotometric detection was set
      lambda=214 nm. Selective fluorescence detection was performed at excitation of
      325 nm and emission of 375 nm. Proposed strategy provides suitable sample
      purification and gives extraction yields in the range of 89-106%. The
      determination coefficient (R(2)) has a value >=0.997 in the range of 50-800 ng/ml
      quinine concentration. The limit of quantification was set at 27.9 ng/ml and the
      detection limit was found to be 8.4 ng/ml under fluorescence detection.

PMID- 25053041
TI  - Cell-based screening assay for anti-inflammatory activity of bioactive compounds.
AB  - Excess dietary intake may induce metabolic inflammation which is associated with
      insulin resistance and cardiovascular disease. Recent evidence indicates that
      dietary bioactive compounds may diminish metabolic inflammation. To identify anti
      inflammatory bioactives, we developed a screening assay using the human H293-NF
      kappaB-RE-luc2P reporter cell line. Under optimised conditions we determined the
      anti-inflammatory activity of vegetables and purified bioactives, by monitoring
      their potency to inhibit TNF-alpha-induced NF-kappaB activity, as assessed by
      sensitive chemiluminescence detection in a 96-well assay format. Minced broccoli
      seedlings reduced NF-kappaB activity by 16%, while sulphoraphane, the dominant
      bioactive in broccoli seedlings, inhibited NF-kappaB activity with an IC50 of
      5.11 MUmol/l. Short-chain fatty acids also reduced NF-kappaB activity in the
      order butyrate>propionate?acetate with IC50 of 51, 223, and 1300 MUmol/l,
      respectively. The H293-NF-kappaB-RE-luc2P reporter cell line is a sensitive tool
      for rapid high-throughput screening for bioactives with anti-inflammatory
      activity.

PMID- 25053042
TI  - A structured approach to target starch solubilisation and hydrolysis for the
      sugarcane industry.
AB  - In sugarcane processing, starch is considered an impurity that negatively affects
      processing and reduces the quality of the sugar end-product. In the last decade,
      there has been a general world-wide increase in starch concentrations in
      sugarcane. Industrial alpha-amylases have been used for many years to mitigate
      issues arising from starch in the sugarcane industry. Mixed results have prompted
      further studies of the behaviour of different physical forms of starch and their
      interactions with alpha-amylases during processing. By using corn starch as a
      reference in model juices and syrups, processing parameters, activities, and
      hydrolysis of insoluble, swollen, and soluble starch forms were evaluated for two
      commercial alpha-amylases with high (HT) and intermediate (IT) temperature
      stability, respectively. The ability of starch to solubilise across a sugarcane
      factory is largely limited by increased Brix values. Optimum target locations and
      conditions for the application of alpha-amylases in sugarcane processing are
      discussed in detail. 

PMID- 25053043
TI  - Profile of the contents of different forms of soybean isoflavones and the effect
      of germination time on these compounds and the physical parameters in soybean
      sprouts.
AB  - The aim of this study was to evaluate the profile of the contents of different
      forms of soybean isoflavones and the effect of germination time on these
      compounds and the physical parameters in BRS 284 soybean sprouts. Soybean seeds
      were germinated for 168 h, and the sprouts were collected every 24 h. The
      physical parameters and contents of different forms of isoflavones of the seeds
      and soybean sprouts were evaluated, and the data were subjected to regression
      analysis. The soybean seeds contained 26.0% beta-glucosides, 72.9%
      malonylglucosides and 1.2% aglycones. The yield of soybean sprouts was 632.4%.
      The effect of germination time was quadratic on the length, moisture and on the
      daidzin, genistin and genistein content; linear on the fresh weight and on the
      malonyldaidzin content. The dry matter and malonylglycitin content was constant,
      and glycitin and glycitein were not detected in the soybean sprouts.

PMID- 25053044
TI  - HPLC-DAD-ESI-MS/MS screening of bioactive components from Rhus coriaria L.
      (Sumac) fruits.
AB  - Rhus coriaria L. (sumac) is an important crop widely used in the Mediterranean
      basin as a food spice, and also in folk medicine, due to its health-promoting
      properties. Phytochemicals present in plant foods are in part responsible for
      these consequent health benefits. Nevertheless, detailed information on these
      bioactive compounds is still scarce. Therefore, the present work was aimed at
      investigating the phytochemical components of sumac fruit epicarp using HPLC-DAD
      ESI-MS/MS in two different ionisation modes. The proposed method provided
      tentative identification of 211 phenolic and other phyto-constituents, most of
      which have not been described so far in R. coriaria fruits. More than 180
      phytochemicals (tannins, (iso)flavonoids, terpenoids, etc.) are reported herein
      in sumac fruits for the first time. The obtained results highlight the importance
      of R. coriaria as a promising source of functional ingredients, and boost its
      potential use in the food and nutraceutical industries. 

PMID- 25053045
TI  - Effect of deastringency treatment of intact persimmon fruits on the quality of
      fresh-cut persimmons.
AB  - The changes in the quality characteristics of the fresh-cut products prepared
      from intact 'Cheongdobansi' persimmons treated with different deastringency
      methods (nontreated, carbon dioxide gas, warm water, ethanol vapour) have been
      investigated for 6 days at 10  degrees C. Flesh firmness of the persimmons
      decreased after ethanol vapour treatment. The decrease in L(*) value and flesh
      firmness in the slices prepared from persimmons treated with warm water was
      retarded. Soluble solids content and titratable acidity of the persimmons
      decreased after all deastringency treatments. Soluble tannins and radical
      scavenging activity of the slices from untreated persimmons were maintained at
      higher concentrations, unlike slices from astringency-removed persimmons. These
      results suggest that pre-slicing deastringency treatments affect the
      characteristics of fresh-cut persimmons, and that warm-water treatment could be a
      useful method to control the browning and softening of fresh-cut persimmons.

PMID- 25053046
TI  - Amperometric detection of Sudan I in red chili powder samples using Ag
      nanoparticles decorated graphene oxide modified glassy carbon electrode.
AB  - A simple and sensitive electrochemical method was developed to determine the
      concentration of Sudan I in chili powder based on silver nanoparticles decorated
      graphene oxide modified glassy carbon electrode (AgNPs@GO/GCE). The voltammetry
      behaviour of Sudan I on modified GCE was investigated in phosphate buffer medium
      (PBS) with various pH ranges and the electron transfer properties were studied.
      It is found that the AgNPs@GO/GCE can catalyse the reduction of azo group, -N=N-
      followed by electrochemical oxidation of (-)OH group present in Sudan I dye
      molecule. Quantitative detection of Sudan I present in food products was carried
      out by amperometry method in which reduction potential was fixed at -0.77 V vs.
      Ag/AgCl. The amperometry method showed an excellent performance with a
      sensitivity of 6.83 MUA mM(-1) and a detection limit of 11.4 * 10(-7)ML(-1). A
      linear calibration graph was constructed in the ranging 3.90 * 10(-6) to 3.19 *
      10(-5)ML(-1). The method was successfully applied for the determination of Sudan
      I in red chili powder samples.

PMID- 25053047
TI  - Agent selection and protective effects during single droplet drying of bacteria.
AB  - The protective mechanisms of whey protein isolate (WPI), trehalose, lactose, and
      skim milk on Lactobacillus plantarum A17 during convective droplet drying has
      been explored. A single droplet drying technique was used to monitor cell
      survival, droplet temperature and corresponding changes in mass. WPI and skim
      milk provided the highest protection amongst the materials tested. In situ
      analysis of the intermediate stage of drying revealed that for WPI and skim milk,
      crust formation reduces the rate of sudden temperature increase thereby imparting
      less stress on the cells. Irreversible denaturation of the WPI components might
      have also contributed to the protection of the cells. Skim milk, however, 'loses'
      the protective behaviour towards the latter stages of drying. This indicates that
      the concentration of the WPI components could be another possible factor
      determining the sustained protective behaviour during the later stages of drying
      when the moisture content is low. 

PMID- 25053048
TI  - Genistein isoflavone glycoconjugates in sour cherry (Prunus cerasus L.)
      cultivars.
AB  - The isoflavone genistein on the contrary to its well-established health
      beneficial effects is not a major component of the Western diet, since soy
      consumption, considered as the main dietary source of genistein, in these
      populations is low. Genistein compounds in twelve commercial sour cherry (Prunus
      cerasus L.) cultivars grown in Hungary were studied. High performance liquid
      chromatography coupled to electrospray ionisation quadrupole/time-of-flight mass
      spectrometry (HPLC-ESI-qToF-MS) was used for screening and confirmatory analyses.
      Genistin and genistein were found in 'Pipacs1', 'Kantorjanosi', 'Debreceni
      botermo' and 'Eva', which are native cultivars to Hungary. Genistein content of
      the latter three were in the range of 0.4-0.6, while in 'Pipacs1' in total 4.4 mg
      genistein compounds were measured expressed as aglycone equivalents per 100g of
      fresh fruit flesh. These cultivars may play important role as complementary
      genistein sources in the Western diet. Especially 'Pipacs 1', may be best
      utilised in functional food products.

PMID- 25053049
TI  - Modelling the effects of orange pomace using response surface design for gluten
      free bread baking.
AB  - The development of gluten-free bread creates many challenges; producing bread
      that will match the properties of its wheat counterpart can be difficult. Fruit
      by-products are know from literature to contain a high level of dietary fibre
      which could improve the bread properties and fibre contents of gluten-free bread.
      Therefore, a mathematical design was created; three variables were identified
      from preliminary tests (water (85-100% flour weight, OP 0-8% flour weight and
      proofing time 35-100 min) as being crucial in the development of acceptable
      bread. Results illustrated longer proofing times (p<0.05) and lower orange pomace
      levels (OP) (p<0.001) produced a bread with a greater specific volume. OP had the
      most significant (p<0.0001) effect on hardness at 2h and 24h post-baking. The
      optimised formulation was calculated to contain 5.5% OP, 94.6% water and a
      proofing time of 49 min. Total fibre content of the control bread (2.1%) was
      successfully increased t o 3.9% in the OP containing bread. Substituting gluten
      free flours with orange pomace flour can help improve the total dietary intake of
      a coeliac while not negating on the quality properties of the bread.

PMID- 25053050
TI  - A cell-penetrating peptide analogue, P7, exerts antimicrobial activity against
      Escherichia coli ATCC25922 via penetrating cell membrane and targeting
      intracellular DNA.
AB  - The antibacterial activities and mechanism of a new P7 were investigated in this
      study. P7 showed antimicrobial activities against five harmful microorganisms
      which contaminate and spoil food (MIC=4-32 MUM). Flow cytometry and scanning
      electron microscopy analyses demonstrated that P7 induced pore-formation on the
      cell surface and led to morphological changes but did not lyse cell. Confocal
      fluorescence microscopic observations and flow cytometry analysis expressed that
      P7 could penetrate the Escherichia coli cell membrane and accumulate in the
      cytoplasm. Moreover, P7 possessed a strong DNA binding affinity. Further cell
      cycle analysis and change in gene expression analysis suggested that P7 induced a
      decreased expression in the genes involved in DNA replication. Up-regulated
      expression genes encoding DNA damage repair. This study suggests that P7 could be
      applied as a candidate for the development of new food preservatives as it exerts
      its antibacterial activities by penetrating cell membranes and targets
      intracellular DNA.

PMID- 25053051
TI  - Analysis of "Amitraz (sum)" in pears with incurred residues - Comparison of the
      approach covering the individual metabolites via LC-MS/MS with the approach
      involving cleavage to 2,4-dimethylaniline.
AB  - We developed a method for the hydrolysis of amitraz, and its degradation products
      2,4-dimethylphenyl-N'-methylformamidine (DMPF) and 2,4-dimethylformamide (DMF)
      into 2,4-dimethylaniline (DMA), directly from QuEChERS extracts. The hydrolysis
      product DMA was analysed using liquid chromatography-electrospray tandem mass
      spectrometry (LC-ESI-MS/MS) in the positive ion mode with DMA D6 as an internal
      standard. Validation of DMPF and amitraz via DMA, following hydrolysis directly
      from the QuEChERS raw extracts, was performed at 0.05 mg kg(-1) and at 0.5 mg kg(
      1). Individual recoveries of amitraz and DMPF, determined as DMA, ranged between
      100 and 120% and between 96 and 118% respectively and the relative standard
      deviations (RSDs) below 5.2% and below 9.5% respectively (n=5 at each spiked
      level). Successful validation for amitraz, and DMPF at 0.01 mg kg(-1), was also
      conducted following fivefold pre-concentration of QuEChERS extracts prior to
      hydrolysis. Pear samples with a history of amitraz treatment, containing residues
      of the amitraz metabolite DMPF but no detectable residues of amitraz or its other
      metabolites, DMF and DMA, were extracted using the QuEChERS method. DMPF-results
      obtained using direct LC-MS/MS analysis were found to be comparable with DMA
      results obtained when the same extracts were subjected to alkaline hydrolysis,
      suggesting that DMPF constituted virtually the only source of DMA in the analysed
      pears and that the determination of amitraz (sum) in pears does not necessarily
      require a cumbersome method involving cleavage to DMA.

PMID- 25053052
TI  - IgE binding to peanut allergens is inhibited by combined D-aspartic and D
      glutamic acids.
AB  - The objective of this study was to determine if D-amino acids (D-aas) bind and
      inhibit immunoglobulin E (IgE) binding to peanut allergens. D-aas such as D-Asp
      (aspartic acid), D-Glu (glutamic acid), combined D-[Asp/Glu] and others were each
      prepared in a cocktail of 9 other D-aas, along with L-amino acids (L-aas) and
      controls. Each sample was mixed with a pooled plasma from peanut-allergic donors,
      and tested by ELISA (enzyme-linked immunosorbent assay) and Western blots for IgE
      binding to peanut allergens. Results showed that D-[Asp/Glu] (4 mg/ml) inhibited
      IgE binding (75%) while D-Glu, D-Asp and other D-aas had no inhibitory effect. A
      higher inhibition was seen with D-[Asp/Glu] than with L-[Asp/Glu]. We concluded
      that IgE was specific for D-[Asp/Glu], not D-Asp or D-Glu, and that D-[Asp/Glu]
      was more reactive than was L-[Asp/Glu] in IgE inhibition. The finding indicates
      that D-[Asp/Glu] may have the potential for removing IgE or reducing IgE binding
      to peanut allergens in vitro.

PMID- 25053053
TI  - Effect of biopolymer encapsulation on the digestibility of lipid and cholesterol
      oxidation products in beef during in vitro human digestion.
AB  - In this study, beef patties were encapsulated with 3% chitosan, pectin, onion
      powder, or green tea powder and the beef patties were then passed through an in
      vitro human digestion model. The total lipid digestibility was lowest (p<0.05) in
      beef patties encapsulated with chitosan and pectin after digestion in the small
      intestine. Thiobarbituric acid reactive substance (TBARS) values were
      significantly lower (p<0.05) for beef patties encapsulated with chitosan and
      pectin, when compared with the control, after digestion in the small intestine.
      In contrast, the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)
      radical-scavenging activity was highest (p<0.05) in beef patties encapsulated
      with onion powder and green tea powder after digestion in the small intestine.
      The total cholesterol oxidation product (COP) content was significantly lower
      (p<0.05) in beef patties encapsulated with biopolymers than in the control after
      digestion in the small intestine. 

PMID- 25053054
TI  - Coffee with ginger - interactions of biologically active phytochemicals in the
      model system.
AB  - This study evaluated the interactions between antiradical and anti-inflammatory
      compounds from coffee and ginger. Results obtained for whole plant material
      extracts were compared with those for chlorogenic and caffeic acids (the main
      hydroxycinnamic acids of plant material). All the tested samples showed the
      ability to scavenge free radicals and to inhibit lipoxygenase (LOX) activity.
      Both of these activities increased after simulated gastrointestinal digestion.
      Aromatic additives, such as ginger, are able to change the antioxidant properties
      of coffee extract and antioxidant interactions may be identified using two
      methods. Antiradical phytochemicals from coffee and ginger acted synergistically 
      isoboles adopted a concave form, while after digestion in vitro an additive
      reaction was observed; in turn, chemical standards acted antagonistically. Water
      extractable LOX inhibitors acted antagonistically; however, after digestion in
      vitro synergism was observed. The same kind of interaction was determined for
      standard compounds. These results were confirmed by IF (interaction factor)
      analysis. 

PMID- 25053055
TI  - Inhibitory effects of cardols and related compounds on superoxide anion
      generation by xanthine oxidase.
AB  - 5-Pentadecatrienylresorcinol, isolated from cashew nuts and commonly known as
      cardol (C15:3), prevented the generation of superoxide radicals catalysed by
      xanthine oxidase without the inhibition of uric acid formation. The inhibition
      kinetics did not follow the Michelis-Menten equation, but instead followed the
      Hill equation. Cardol (C10:0) also inhibited superoxide anion generation, but
      resorcinol and cardol (C5:0) did not inhibit superoxide anion generation. The
      related compounds 3,5-dihydroxyphenyl alkanoates and alkyl 2,4
      dihydroxybenzoates, had more than a C9 chain, cooperatively inhibited but alkyl
      3,5-dihydroxybenzoates, regardless of their alkyl chain length, did not inhibit
      the superoxide anion generation. These results suggested that specific inhibitors
      for superoxide anion generation catalysed by xanthine oxidase consisted of an
      electron-rich resorcinol group and an alkyl chain having longer than C9 chain.

PMID- 25053056
TI  - Development of magnetic micro-solid phase extraction for analysis of phthalate
      esters in packaged food.
AB  - A novel, simple and low cost magnetic multi-walled carbon nanotubes-poly (vinyl
      alcohol) cryogel-micro-solid phase extraction (magnetic-MWCNTs-PVA cryogel-MU
      SPE) sorbent was synthesized by incorporating magnetic particles and MWCNTs into
      a PVA cryogel. The magnetic-MWCNTs-PVA cryogel-MU-SPE sorbent developed, with a
      large surface area and macro-porous structure, provided good sorbent-to-sorbent
      reproducibility (%RSD<8) and each sorbent could be used up to 30 times (%RSD<6).
      This sorbent was applied for the extraction of dibutyl phthalate (DBP) and di-2
      (ethylhexyl) phthalate (DEHP) in packaged food prior to analysis by gas
      chromatograph coupled with flame ionisation detector (GC-FID). The concentration
      of DBP and DEHP in hot-water samples from plastic bags were found in the range
      0.04-0.15 MUg mL(-1) and 0.03-0.20 MUg mL(-1), respectively, but only DEHP was
      found in clear chicken soup samples in the range 0.02-0.07 MUg mL(-1).

PMID- 25053057
TI  - Fluorometric determination of free glucose and glucose 6-phosphate in cows' milk
      and other opaque matrices.
AB  - Analyses of free glucose and glucose 6-phosphate in milk have until now been
      dependent upon several time consuming and troublesome procedures. This has
      limited investigations in the area. The present article presents a new, reliable,
      analytical procedure, based on enzymatic degradation and fluorometric detection.
      Standards and control materials were based on milk that was stripped of intrinsic
      glucose and glucose 6-phosphate in order to obtain standards and samples based on
      the same matrix. The analysis works without pre-treatment of the samples, e.g.
      without centrifugation and precipitation of protein with acids. 

PMID- 25053058
TI  - Kinetic modeling of pressure-assisted solvent extraction of polyphenols from
      green tea in comparison with the conventional extraction.
AB  - In the study, the kinetics of pressure-assisted solvent extraction (PSE) of
      polyphenols from green tea at different pressures (300, 400, 500 MPa) was
      studied. The model derived from Patricelli, which describes the two step
      extraction consisting of rapid washing followed by slow diffusion, had been
      applied to estimate the extraction kinetics. The model parameters were calculated
      using the experimental results obtained from PSE and conventional solvent
      extraction (CSE). The results showed a good prediction of Patricelli's model for
      extraction kinetics in all experiments (R(2)>=0.996), which gave the possibility
      for estimation of the extraction rate and extent of PSE. The results also showed
      that the extraction by washing was more efficient with PSE than CSE. In addition,
      the initial extraction rate of the PSE was always much larger than that of the
      CSE. Therefore, PSE was more effective for extracting the green tea polyphenols
      than the CSE.

PMID- 25053059
TI  - Potential of LC-MS phenolic profiling combined with multivariate analysis as an
      approach for the determination of the geographical origin of north Moroccan
      virgin olive oils.
AB  - The applicability of two different platforms (LC-ESI-TOF MS and LC-ESI-IT MS) as
      powerful tools for the characterisation and subsequent quantification of the
      phenolic compounds present in north Moroccan virgin olive oils was assessed in
      this study. 156 olives samples of "Picholine Marocaine" cultivar grown in 7
      Moroccan regions were collected and olive oils extracted. The phenolic profiles
      of these olive oils were studied using a resolutive chromatographic method
      coupled to ESI-TOF MS (for initial characterisation purposes) and coupled to ESI
      IT MS (for further identification and quantification). 25 phenolic compounds
      belonging to different chemical families were identified and quantified.
      Secoiridoids were the most abundant phenols in all the samples, followed by
      phenolic alcohols, lignans and flavonoids, respectively. For testing the ability
      of phenolic profiles for tracing the geographical origin of the investigated
      oils, multivariate analysis tools were used, getting a good rate of correct
      classification and prediction by using a cross validation procedure. 

PMID- 25053060
TI  - Mechanism of chemical activation of sodium chloride in the presence of amino
      acids.
AB  - Sodium chloride has been shown to promote chlorination of glycerol during thermal
      processing. However, the detailed mechanism of this reaction is not well
      understood. Preliminary experiments have indicated that the reaction mixture
      should contain an amino acid and it should be dissolved thoroughly in water in
      order to induce chlorination. These observations are consistent with the process
      of dissociation of sodium chloride and its re-association with amino acid and
      eventual formation of the chlorinating agent in the form of the hydrochloride
      salt. Release of HCl from this salt can be manifested in chlorination and
      hydrolytic reactions occurring during thermal processing. The generation of HCl
      at room temperature from a mixture of sodium chloride and glycine was confirmed
      through spectrophotometric monitoring of the pH. Hydrolytic and chlorination
      reactions were demonstrated through monitoring of formation of HMF and
      chlorinated products under pyrolytic conditions using glucose or sucrose and
      amino acid mixtures. 

PMID- 25053061
TI  - Screening and determination of sulphonamide residues in bovine milk samples using
      a flow injection system.
AB  - A new, simple, rapid and sensitive flow injection spectrophotometric method was
      developed for the screening and determination of sulphonamides in bovine milk
      samples. The method is based on the condensation of sulphathiazole,
      sulphamethazine, and sulphadimethoxine with p-dimethylaminobenzaldehyde (p-DAB)
      in acid medium, in the presence of sodium dodecyl sulphate (SDS), producing a
      yellow compound (lambdamax=465 nm). Optimisation of the experimental parameters
      was performed using a multivariate methodology. The linear range was 90-500 MUg/L
      and the limits of detection and quantification were in the ranges 25-29 MUg/L and
      84-88 MUg/L, respectively. The procedure was applied for the determination of
      sulphonamide antibiotics in bovine milk samples submitted to a prior extraction
      procedure based on QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe)
      methodology. Recoveries of 60.5-70.5% were achieved for milk samples spiked with
      0.09, 0.1, 0.2, and 0.3 MUg/g of each sulphonamide.

PMID- 25053062
TI  - Simultaneous extraction of oil- and water-soluble phase from sunflower seeds with
      subcritical water.
AB  - In this study, the subcritical water extraction is proposed as an alternative and
      greener processing method for simultaneous removal of oil- and water-soluble
      phase from sunflower seeds. Extraction kinetics were studied at different
      temperatures and material/solvent ratios in a batch extractor. Degree of
      hydrothermal degradation of oils was observed by analysing amount of formed free
      fatty acids and their antioxidant capacities. Results were compared to oils
      obtained by conventional methods. Water soluble extracts were analysed for total
      proteins, carbohydrates and phenolics and some single products of hydrothermal
      degradation. Highest amount of oil was obtained at 130  degrees C at a
      material/solvent ratio of 1/20 g/mL after 30 min of extraction. For all obtained
      oils minimal degree of hydrothermal degradation could be identified. High
      antioxidant capacities of oil samples could be observed. Water soluble extracts
      were degraded at temperatures >=100  degrees C, producing various products of
      hydrothermal degradation.

PMID- 25053063
TI  - Determination of the antiradical properties of olive oils using an
      electrochemical method based on DPPH radical.
AB  - The present work describes the development of an electrochemical method based on
      the use of 2,2'-diphenyl-1-picrylhidrazyl free radical (DPPH) for the
      determination of the antiradical properties of several olive oils. Differential
      pulse voltammetry was used as measuring technique while the electrochemical
      process was recorded at a platinum screen-printed working electrode. The decrease
      in 2,2'-diphenyl-1-picrylhidrazyl peak current intensity was measured at a
      specific potential value of +160 mV vs. screen-printed pseudo-reference
      electrode, in the presence of alpha-, delta- and gamma-tocopherol and olive oil
      samples, respectively. The obtained results using differential pulse voltammetry,
      as detection technique for real samples analysis, showed a satisfactory agreement
      with those obtained by high-performance liquid chromatography coupled with
      fluorescence detection. The reported electrochemical method is rapid and easy to
      use, feasible and accessible to be used as an alternative to 2,2'-diphenyl-1
      picrylhidrazyl spectrophotometric based method.

PMID- 25053064
TI  - Antifungal activity and inhibition of fumonisin production by Rosmarinus
      officinalis L. essential oil in Fusarium verticillioides (Sacc.) Nirenberg.
AB  - The chemical composition of Rosmarinus officinalis L. essential oil (REO) was
      analysed by gas chromatography-mass spectrometry and nuclear magnetic resonance
      spectroscopy. The main compounds of the REO were 1.8 cineole (52.2%), camphor
      (15.2%) and alpha-pinene (12.4%). The mycelial growth of Fusarium verticillioides
      (Sacc.) Nirenberg was reduced significantly by 150 MUg/mL of REO. Significant
      microscopic morphological changes were visualised, such as the rupture of the
      cell wall and the leakage of cytoplasm at 300 MUg/mL of REO. At lower
      concentrations of REO, the effects on the production of ergosterol and the
      biomass of mycelium varied, as did the effects on the production of fumonisins,
      but at >=300 MUg/mL of REO, these processes were significantly inhibited, showing
      the effectiveness of the REO as an antifungal agent. The results suggested that
      the REO acts against F. verticillioides by disrupting the cell wall and causing
      the loss of cellular components, subsequently inhibiting the production of
      fumonisins and ergosterol.

PMID- 25053065
TI  - Fluorescent labeling of cranberry proanthocyanidins with 5-([4,6-dichlorotriazin
      2-yl]amino)fluorescein (DTAF).
AB  - A novel methodology was developed to elucidate proanthocyanidins (PAC)
      interaction with extra-intestinal pathogenic Escherichia coli (ExPEC). PAC
      inhibit ExPEC invasion of epithelial cells and, therefore, may prevent transient
      gut colonization, conferring protection against subsequent extra-intestinal
      infections, such as urinary tract infections. Until now PAC have not been
      chemically labeled with fluorophores. In this work, cranberry PAC were labeled
      with 5-([4,6-dichlorotriazin-2-yl]amino) fluorescein (DTAF), detected by high
      performance liquid chromatography with diode-array detection and characterized by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). We report single and double fluorescent-labeled PAC with one or
      two chlorine atoms displaced from DTAF in alkaline pH via nucleophilic
      substitution. Fluorescent labeling was confirmed by fragmentation experiments
      using MALDI-TOF/TOF MS. Fluorescent labeled PAC were able to promote ExPEC
      agglutination when observed with fluorescence microscopy. DTAF tagged PAC may be
      used to trace the fate of PAC after they agglutinate ExPEC and follow PAC-ExPEC
      complexes in cell culture assays. 

PMID- 25053066
TI  - Oxidative stability of high-oleic sunflower oil in a porous starch carrier.
AB  - This study evaluates the oxidation level of high-oleic sunflower oil (HOSO)
      plated onto porous starch as an alternative to spray drying. Encapsulated oils
      were subjected to accelerated oxidation by heat and light exposure, and peroxide
      value (PV) and conjugated dienes (CD) were measured. Bulk oil was the control. PV
      increased in all samples with increased light exposure, with similar values being
      reached by oil carried on porous starch and spray dried oil. The encapsulation
      processes determined a reduced effect of light on the increase of CD in the oil,
      as compared to bulk oil. Spray dried oil presented the highest CD in the
      experimental domain considered. Since similar levels of PV and lower levels of CD
      were shown in the HOSO carried on porous starch compared to the spray dried HOSO,
      plating flavour oils on porous starch could be a suitable technological
      alternative to spray drying, for flavour encapsulation. 

PMID- 25053067
TI  - Highly-sensitive and rapid detection of ponceau 4R and tartrazine in drinks using
      alumina microfibers-based electrochemical sensor.
AB  - Alumina microfibers were prepared and used to construct an electrochemical sensor
      for simultaneous detection of ponceau 4R and tartrazine. In pH 3.6 acetate
      buffer, two oxidation waves at 0.67 and 1.01 V were observed. Due to porous
      structures and large surface area, alumina microfibers exhibited high
      accumulation efficiency to ponceau 4R and tartrazine, and increased their
      oxidation signals remarkably. The oxidation mechanisms were studied, and their
      oxidation reaction involved one electron and one proton. The influences of pH
      value, amount of alumina microfibers and accumulation time were examined. As a
      result, a highly-sensitive, rapid and simple electrochemical method was newly
      developed for simultaneous detection of ponceau 4R and tartrazine. The detection
      limits were 0.8 and 2.0 nM for ponceau 4R and tartrazine. This new sensor was
      used in different drink samples, and the results consisted with the values that
      obtained by high-performance liquid chromatography.

PMID- 25053068
TI  - Effects of drying methods on the tasty compounds of Pleurotus eryngii.
AB  - The aim of this research was to study effects of drying methods on the tasty
      compounds of Pleurotus eryngii, a common commercial edible fungus. In order to
      maximally maintain the taste of P. eryngii, several different drying methods,
      including hot air, vacuum, microwave, freeze drying and naturally air-drying,
      were compared. Results showed that freeze drying and hot air were capable of the
      conservation of the taste compounds maximally in P. eryngii, followed by natural
      air drying and vacuum, while microwave drying was not suitable for P. eryngii due
      to the loss of taste compounds. Moreover, concentrations of free amino acids in
      freeze drying were significantly reduced, so as to 5'-nucleotides in hot air
      drying. In addition, the umami concentration of the sample using hot air dry was
      significantly (p<0.05) higher than that using microwave. 

PMID- 25053069
TI  - In vitro bioaccessibility of beta-carotene, Ca, Mg and Zn in landrace carrots
      (Daucus carota, L.).
AB  - Four landrace carrots ("Becaria", "CRS", "Gonzalez" and "Rodriguez") and two
      marketable cultivars (Kuroda and Brasilia), raw and steamed, were characterised
      by the total content of beta-carotene Ca, Mg and Zn, in vitro bioaccessibility
      and by colour and were evaluated to determine the effect of particle size in
      nutrient bioaccessibility. Steaming increased the content of beta-carotene
      extracted from "CRS" and Brasilia (29% and 75%) and decreased the content of beta
      carotene extracted from "CRS" by 23% in "Rodriguez." In addition, steaming caused
      a loss of Ca (21%) but did not change the amount of Mg and Zn. The
      bioaccessibility of beta-carotene in raw and pulped carrots was very low (<0.5%).
      Furthermore, steaming and a smaller particle size increased the bioaccessibility
      of beta-carotene by 3-16 times. Additionally, cooking increased the in vitro
      bioaccessibility of Ca and Zn but had no effect on Mg. Moreover, homogenisation
      increased the bioaccessibility by 20% in Ca, 17% in Mg, and 10% in Zn compared to
      pulping. 

PMID- 25053070
TI  - An enzyme-linked chemiluminescent immunoassay developed for detection of
      Butocarboxim from agricultural products based on monoclonal antibody.
AB  - In this study, four different haptens around the oxime moiety of Butocarboxim
      were designed and synthesised. Two of the haptens were conjugated with bovine
      serum albumin (BSA) to serve as the immunogen and all the haptens were conjugated
      with ovalbumin (OVA) for the coating antigen. The anti-Butocarboxim monoclonal
      antibody (Mab) was selected based on eight immunogen/coating antigen
      combinations. The first enzyme-linked chemiluminescent immunoassay (ELCIA) for
      determining Butocarboxim in agricultural products was developed. Under the
      optimised conditions, the detection limit for the ELCIA was 20 ng.mL(-1) and the
      linear range was 27-2700 ng.mL(-1). Analyte recoveries for extracts of spiked
      agricultural (apple and greengrocery) products and tap water ranged from 97.18%
      to 107.00%. The developed immunoassay has great potential to be developed as a
      test kit offering a simple and cost-effective approach (such as lateral flow test
      strip) for screening purposes and evaluating environmental exposure to
      Butocarboxim.

PMID- 25053071
TI  - Characterisation of phenolics, betanins and antioxidant activities in seeds of
      three Chenopodium quinoa Willd. genotypes.
AB  - Quinoa (Chenopodium quinoa Willd.) is known for its exceptional nutritional value
      and potential health benefits. The present study identified the composition of
      different forms of extractable phenolics and betacyanins of quinoa cultivars in
      white, red and black, and how they contribute to antioxidant activities. Results
      showed that at least 23 phenolic compounds were found in either free or
      conjugated forms (liberated by alkaline and/or acid hydrolysis); the majority of
      which were phenolic acids, mainly vanillic acid, ferulic acid and their
      derivatives as well as main flavonoids quercetin, kaempferol and their
      glycosides. Betacyanins, mainly betanin and isobetanin, were confirmed for the
      first time to be the pigments of the red and black quinoa seeds, instead of
      anthocyanins. Darker quinoa seeds had higher phenolic concentration and
      antioxidant activity. Findings of these phenolics, along with betacyanins in this
      study add new knowledge to the functional components of quinoa seeds of different
      cultivar background. 

PMID- 25053072
TI  - Rapid metabolic discrimination and prediction of dioscin content from African yam
      tubers using Fourier transform-infrared spectroscopy combined with multivariate
      analysis.
AB  - To determine whether or not FT-IR spectroscopy could be used for taxonomic and
      metabolic discrimination of African yam lines, tuber samples from African and
      Asian yam species were subjected to FT-IR. Most remarkable spectral differences
      between African and Asian yams were found in the 1750-1700 cm(-1) region,
      polysaccharide (1200-900 cm(-1)) and protein/amide I and II (1700-1500 cm(-1))
      regions of FT-IR spectra. A hierarchical dendrogram based on partial least square
      discriminant analysis (PLS-DA) of FT-IR data from 7 African yam species show
      phylogenetic relationship. In addition, the content of dioscin, a steroidal
      saponin found in yam tuber, was predicted using a PLS regression model with
      regression coefficient R(2)=0.7208 indicated that prediction model had average
      accuracy. Thus, considering these results we suggest that FT-IR combined with
      multivariate analysis could be applied as a novel tool for metabolic evaluation
      and high-throughput screening of African yam lines with higher content of
      dioscin.

PMID- 25053073
TI  - Acylated anthocyanins from sprouts of Raphanus sativus cv. Sango: isolation,
      structure elucidation and antioxidant activity.
AB  - Little is known on structure-activity relationships of antioxidant anthocyanins.
      Raphanus sativus cv Sango sprouts are among the richest sources (270 mg/100 g
      fresh weight). We isolated from sprouts' juice 9 acylated anthocyanins, including
      4 new compounds. All comprise a cyanidin core bearing 3-4 glucose units, multiply
      acylated with malonic and phenolic acids (ferulic and sinapic). All compounds
      were equally effective in inhibiting the autoxidation of linoleic acid in aqueous
      micelles, with rate constant for trapping peroxyl radicals kinh=(3.8 +/- 0.7) *
      10(4)M(-1)s(-1) at 37  degrees C. In acetonitrile solution kinh varied with
      acylation: (0.9-2.1) * 10(5)M(-1)s(-1) at 30  degrees C. Each molecule trapped a
      number n of peroxyl radicals ranging from 4 to 7. Anthocyanins bearing sinapic
      acid were more effective than those bearing the ferulic moiety. Under identical
      settings, deacylated cyanin, ferulic and sinapic acids had kinh of 0.4 * 10(5),
      0.3 * 10(5) and 1.6 * 10(5)M(-1)s(-1) respectively, with n ranging 2-3. Results
      show the major role of acylation on antioxidant performance.

PMID- 25053074
TI  - Bioactivity of Meeker and Willamette raspberry (Rubus idaeus L.) pomace extracts.
AB  - Taking into account the substantial potential of raspberry processing by
      products, pomace extracts from two raspberry cultivars, Meeker and Willamette,
      were investigated. Total phenolic, flavonoid and anthocyanin contents were
      determined. Willamette pomace extract (EC50=0.042 mg/ml) demonstrated stronger
      2,2-diphenyl-1-picrylhydrazyl DPPH radical-scavenging activity than did Meeker
      pomace extract (EC50=0.072 mg/ml). The most pronounced cell growth inhibition
      effect was obtained in the breast adenocarcinoma cell line, reaching EC50 values
      of 34.8 and 60.3 MUg/ml for Willamette and Meeker extracts, respectively. Both
      extracts demonstrated favourable non-tumor/tumor cell growth ratios and potently
      increased the apoptosis/necrosis ratio in breast adenocarcinoma and cervix
      carcinoma cells. In reference and wild bacterial strains, minimal inhibitory
      concentrations (MIC) were achieved in a concentration range from 0.29 to 0.59
      mg/ml, and minimal bactericidal concentrations (MBC) in a range from 0.39 to 0.78
      mg/ml. The results indicate significant antioxidant, antiproliferative,
      proapoptotic and antibacterial activities of raspberry pomace and favour its use
      as a functional food ingredient.

PMID- 25053075
TI  - Transglutaminase-induced crosslinking of gelatin-calcium carbonate composite
      films.
AB  - The effects of transglutaminase (TGase) on the rheological profiles and
      interactions of gelatin-calcium carbonate solutions were studied. In addition,
      mechanical properties, water vapour permeability and microstructures of gelatin
      calcium carbonate films were also investigated and compared. Fluorescence data
      suggested that the interaction of TGase and gelation-calcium carbonate belonged
      to a static quenching mechanism, and merely one binding site between TGase and
      gelatin-calcium carbonate was identified. Moreover, differential scanning
      calorimetry (DSC), the mechanical properties and the water vapour permeability
      studies revealed that TGase favoured the strong intramolecular polymerisation of
      the peptides in gelatin. The microstructures of the surfaces and cross sections
      in gelatin-calcium carbonate films were shown by scanning electron microscope
      (SEM) micrographs. The results of the fourier transform infrared spectroscopy
      (FTIR) indicated that TGase caused conformational changes in the proteins films.
      Therefore, TGase successfully facilitated the formation of gelatin-calcium
      carbonate composite films. 

PMID- 25053076
TI  - Cytotoxic and mutagenic in vitro assessment of two organosulfur compounds derived
      from onion to be used in the food industry.
AB  - Edible members of the Allium family are widely used since they exhibit
      antioxidant and antibacterial related to the organosulphur compounds. One the
      most promising use of Allium species, hence, onion essential oil, could be in the
      packaging food industry. The present work aims to assess the safety of two
      organosulphur compounds present in onion essential oil; dipropyl disulphide,
      dipropyl sulphide and their mixture. For this purpose, cytotoxicity, reactive
      oxygen species and glutathione contents, and ultrastructural cellular damages
      were studied in the human intestinal cells, Caco-2, exposed to these
      organosulphur compounds. Moreover, their potential mutagenicity was also
      assessed. The results revealed no significant adverse effects. Additionally,
      reactive oxygen species scavenger activity was observed for both compounds.
      Therefore, they could be a good natural alternative to other synthetic
      antioxidant and antibacterial substances used in the food industry. 

PMID- 25053077
TI  - Determination of total mercury in fish and sea products by direct thermal
      decomposition atomic absorption spectrometry.
AB  - A Zeeman Mercury analyzer Model RA-915(+) (Lumex, St. Petersburg, Russia), based
      on the direct thermal evaporation of Hg from solid samples was used for
      developing a method for the determination of Hg in fish and other seafood. The
      method does not require any chemical pretreatment of samples. This greatly
      simplifies the analytical procedure and minimises potential sources of
      contamination. The limit of detection (3s criteria) and limit of quantification
      (10 s criteria) for the determination of Hg in wet fish samples with a mass of
      250 mg was found to be 0.6 ng g(-1) and 2.0 ng g(-1), respectively. Time taken
      for the analysis of one sample is about 3 min. The accuracy of the method was
      confirmed by the analysis of certified reference materials of different types and
      by comparative analysis of fish samples using the accepted method of cold vapour
      generation. Excellent correspondence to the certified values was obtained. It was
      found that the mercury concentration in most fish species purchased from the
      Tshwane fish market were below the 0.5 mg kg(-1) (500 ng g(-1)), wet weight,
      recommended by the FAO/WHO. It was also found that the direct thermal
      decomposition method for the determination of mercury is a more environmentally
      friendly alternative since it does not generate chemical waste.

PMID- 25053078
TI  - Precursor ion scan driven fast untargeted screening and semi-determination of
      caffeoylquinic acid derivatives in Cynara scolymus L.
AB  - A precursor ion scan (PIS) technique based strategy was developed for rapid
      screening and semi-determination of caffeoylquinic acid derivatives (CADs) in
      artichoke (Cynara scolymus L.) using ultra-performance liquid chromatography
      (UPLC) coupled with tandem mass spectrometry. 1,5-Dicaffeoylquinic acid and 5
      caffeoylquinic acid were used for studying the fragmentation behaviour of two
      classes of CADs, setting m/z 191 as a diagnostic moiety. When it was applied to
      artichoke sample, ten CADs were detected and elucidated in a single PIS run.
      Furthermore, method validation was implemented including: specificity (no
      interference), linearity (>=0.9993), limit of detection (LOD<0.12 ng mL(-1)) and
      limit of quantification (LOQ<0.25 ng mL(-1)), precision (RSD<=3.6), recovery
      (91.4-95.9%) and stability (at least 12 h). This approach was proven to be a
      powerful, selective and sensitive tool for rapid screening and semi-determination
      of untargeted components in natural products.

PMID- 25053079
TI  - Tracing flavonoid degradation in grapes by MS filtering with stable isotopes.
AB  - Anthocyanin degradation has been proposed as one of the primary causes for
      reduced colour and quality in red wine grapes grown in a warm climate. To study
      anthocyanin degradation we infused berries with L-phenyl-(13)C6-alanine and then
      tracked the fate of the anthocyanins comparing normal (25  degrees C) and warm
      (45  degrees C) temperature conditions. An untargeted metabolomics approach was
      aided by filtering the MS data using software algorithms to extract all M and M+6
      isotopic peak pairs, allowing the analysis to focus solely on the metabolites of
      phenylalanine. A paired-comparison t-test was performed over the 8 biological
      replicates revealing 13 metabolites that were statistically different between 25 
      degrees C and 45  degrees C treatments. Most of these features had lower
      abundances in 45  degrees C samples, confirming that 45  degrees C treatment
      caused anthocyanin degradation. In addition, resveratrol was significantly
      reduced following heat treatment. However, 5 metabolites increased following the
      45  degrees C treatment. These unidentified metabolites are therefore suspects
      for anthocyanin degradation products.

PMID- 25053080
TI  - Development of a reliable extraction and quantification method for glucosinolates
      in Moringa oleifera.
AB  - Glucosinolates are the characteristic secondary metabolites of plants in the
      order Brassicales. To date the common DIN extraction 'desulfo glucosinolates'
      method remains the common procedure for determination and quantification of
      glucosinolates. However, the desulfation step in the extraction of glucosinolates
      from Moringa oleifera leaves resulted in complete conversion and degradation of
      the naturally occurring glucosinolates in this plant. Therefore, a method for
      extraction of intact Moringa glucosinolates was developed and no conversion and
      degradation of the different rhamnopyranosyloxy-benzyl glucosinolates was found.
      Buffered eluents (0.1 M ammonium acetate) were necessary to stabilize 4-alpha
      rhamnopyranosyloxy-benzyl glucosinolate (Rhamno-Benzyl-GS) and acetyl-4-alpha
      rhamnopyranosyloxy-benzyl glucosinolate isomers (Ac-Isomers-GS) during HPLC
      analysis. Due to the instability of intact Moringa glucosinolates at room
      temperature and during the purification process of single glucosinolates,
      influences of different storage (room temperature, frozen, thawing and
      refreezing) and buffer conditions on glucosinolate conversion were analysed.
      Conversion and degradations processes were especially determined for the Ac
      Isomers-GS III.

PMID- 25053081
TI  - Development of polysaccharides-based edible coatings for citrus fruits: a layer
      by-layer approach.
AB  - Biodegradable coatings for citrus fruits that would replace the currently used
      polyethylene-based waxes, are of great interest. Methylcellulose (MC),
      hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC) and chitosan
      (CH) coatings were examined on the most sensitive citrus fruit model: mandarins.
      Among the examined polysaccharides, CMC provided mandarins with the best
      firmness, lowest weight loss and satisfying gloss, while not affecting natural
      flavour and the respiration process. To enhance coating performance, glycerol,
      oleic acid and stearic acid were added; however, mandarin quality generally
      deteriorated with these additives. Then, a layer-by-layer (LBL) approach was
      applied. LbL coatings, based on a combination of two polysaccharides, CMC as an
      internal layer and chitosan as an external layer, gave the best performance.
      Different concentrations of chitosan were examined. The LbL coatings notably
      improved all quantified parameters of fruit quality, proving that polysaccharide
      based edible coating may offer an alternative to synthetic waxes. 

PMID- 25053082
TI  - Molecular species analysis of monosialogangliosides from sea urchin
      Strongylocentrotus nudus by RPLC-ESI-MS/MS.
AB  - Sea urchin gangliosides have been proved to contain neuritogenic activities,
      which related to their molecular compositions. This study reports a method
      utilizing reversed-phase chromatography coupled to mass spectrometry for
      structure investigation and molecular species determination of the
      monosialogangliosides from sea urchin Strongylocentrotus nudus. Two types of
      sulfated and nonsulfated monosialogangliosides were isolated from the sea urchin
      ovary. In MS(2) spectra of both nonsulfated monosialoganglioside and sulfated
      monosialoganglioside, 2-6 linked sialic acids were identified by the
      characteristic fragments of (0,4)A2-CO2 and (0,2)A1. Fragment ions at m/z 139.1
      and m/z 169.1 of nonsulfated monosialoganglioside might be characteristic for 8
      sulfated sialic acid residue. Retention time of the molecules was effectively
      used in the characterization of unknown molecules, and molecules that differ in
      mass by only 0.04 Da were easily differentiated.

PMID- 25053083
TI  - Characterization of gold kiwifruit pectin from fruit of different maturities and
      extraction methods.
AB  - Studies on gold kiwifruit pectins are limited. In this work, the characterization
      of pectin isolated from two different stages of maturity of gold kiwifruit,
      namely early harvested fruit (EHF) and main harvested fruit (MHF) isolated by
      three methods (acid, water, enzymatic) was carried out. Pectins isolated from MHF
      were higher in galacturonic acid content (52-59% w/w) and weight-average
      molecular weights (Mw, 1.7-3.8 * 10(6)g/mol) compared with EHF pectins (29-49%
      w/w and 0.2-1.7 * 10(6)g/mol respectively). Enzymatic treatment gave the highest
      yield but lowest in Mw, viscosity and mechanical spectra for both maturities. The
      pectin of both maturities was classified as high-methoxyl pectin with the degree
      of esterification ranged from 82% to 90%. Water-extracted MHF pectin molecules
      had the highest RMS radius (182.7 nm) and Mw (3.75 * 10(6)g/mol). The water
      extraction method appeared to retain the native state of pectin molecules
      compared with acid and enzymatic extraction methods based on the Mw and viscosity
      data.

PMID- 25053084
TI  - Content and evolution of potential furfural compounds in commercial milk-based
      infant formula powder after opening the packet.
AB  - Potential furfural compounds were examined by RP-HPLC-DAD in 20 commercial milk
      based powdered infant formula (IF) brands from local markets from Paris, France;
      DF, Mexico; Copenhagen, Denmark; England, UK; and Barcelona, Spain. We traced the
      evolution of these compounds after the packets had been opened at 0, 30 and 70
      days of storage at room temperature (~25  degrees C; minimum 23  degrees C and
      maximum 25.5  degrees C). All formula brands were analysed during the first 3-5
      months of their shelf life. The mean values of all IFs for potential 5
      hydroxymethyl-2-furaldehyde (HMF)+2-furaldehyde (F) were 1115.2 MUg/100 g (just
      opened), 1157.6 MUg/100 g (30 days) and 1344.5 MUg/100 g of product (70 days). In
      general, slight increases of potential furfural contents were observed in most of
      the studied IFs, which suggests that the Maillard reaction increases after
      opening the packets. The main furfural compound found was HMF, as expected. The
      range of potential HMF consumed for an infant about 6 months old feeding only on
      formula was estimated between 0.63 mg and 3.25 mg per day.

PMID- 25053085
TI  - Metal ions bound to the human milk immunoglobulin A: metalloproteomic approach.
AB  - The presence of calcium, iron, and zinc bound to human milk secretory IgA (sIgA)
      was investigated. The sIgA components were first separated by two-dimensional
      polyacrylamide gel electrophoresis and then identified by electrospray ionization
      tandem mass spectrometry (ESI MS MS). The metal ions were detected by flame
      atomic absorption spectrometry after acid mineralization of the spots. The
      results showed eight protein spots corresponding to the IgA heavy chain constant
      region. Another spot was identified as the transmembrane secretory component.
      Calcium was bound to both the transmembrane component and the heavy chain
      constant region, while zinc was bound to the heavy chain constant region and iron
      was not bound with the identified proteins. The association of a metal ion with a
      protein is important for a number of reasons, and therefore, the findings of the
      present study may lead to a better understanding of the mechanisms of action and
      of additional roles that sIgA and its components play in human milk. 

PMID- 25053086
TI  - Impact of enzymatic method using crude protease from Pacific white shrimp
      hepatopancreas on the extraction efficiency and compositions of lipids.
AB  - Lipids from striped catfish muscle were extracted with the aid of crude protease
      extract (CPE) from hepatopancrease of Pacific white shrimp at different levels (5
      15 unit/g protein) for various hydrolysis times (0-180 min) at 60  degrees C.
      Yield of lipids increased within the first 30 min and was in agreement with
      increasing degree of hydrolysis. The increases in phospholipid and free fatty
      acid content were observed with hydrolysis times up to 30 min (p<0.05). Yield of
      lipid increased when 50mM CaCl2 was combined with CPE. CPE exhibited similar
      extraction efficiency to Alcalase. However, the lower yield was obtained in
      comparison with the solvent extraction. Higher oxidation and hydrolysis were
      found in lipids extracted with the aid of CPE and Alcalase, compared with those
      found in lipid extracted using solvents (p<0.05). All lipid samples had
      triglyceride as the major component and were rich in palmitic acid and oleic
      acid.

PMID- 25053087
TI  - Phenolic profiles in leaves of chicory cultivars (Cichorium intybus L.) as
      influenced by organic and mineral fertilizers.
AB  - Chicory (Cichorium intybus L.) is a typical Mediterranean vegetable, and it shows
      great morphological diversity, including different leaf colours. Five cultivars
      commonly produced in Slovenia ('Treviso', 'Verona', 'Anivip', 'Castelfranco',
      'Monivip') were grown in pots under controlled conditions in a glasshouse, with
      organic and/or mineral fertilizers administered to meet nitrogen requirements.
      HPLC analysis was carried out to study the phenolic compositions of the leaves. A
      total of 33 phenolic compounds were extracted from these chicory leaves and were
      quantitatively evaluated in an HPLC-DAD-based metabolomics study. Among the
      cultivars, the highest TPC was seen for 'Treviso' (300.1 mg/100 g FW), and the
      lowest, for 'Castelfranco' (124.9 mg/100g FW). Across the different treatments,
      the highest TPC was in the control samples (254.3 mg/100 g FW), and the lowest
      for the organic (128.6 mg/100 g FW) and mineral fertilizer (125.5 mg/100 g FW)
      treatments. The predominant phenolic compounds in all of the samples were
      hydroxycinnamic acids, including chlorogenic and cichoric acid. Fertilizer
      administration provides a discriminant classification of the chicory cultivars
      according to their phenolic compounds.

PMID- 25053088
TI  - The effects of plant growth regulators and L-phenylalanine on phenolic compounds
      of sweet basil.
AB  - The effects of methyl jasmonate (MeJA), spermine (Spm), epibrassinolide (EBL) and
      l-phenylalanine on sweet basil (Ocimum basilicum L.) were studied to determine
      the amount of phenolic compounds and enzymatic activity of phenylalanine ammonia
      lyase (PAL). Total phenolic and total flavonoid contents of sweet basils were
      determined by a spectrophotometer, and individual phenolic compounds and activity
      of PAL were analysed by HPLC/UV. The highest total phenolic (6.72 mg GAE/g) and
      total flavonoid contents (0.92 mg QE/g) obtained from 1.0 mM Spm+MeJA
      application. Rosmarinic acid (RA) and caffeic acid contents significantly
      enhanced after the applications but no such differences observed in chicoric acid
      content or PAL activity. RA was the main phenolic acid in all samples and its
      concentration varied from 1.04 to 2.70 mg/gFW. As a result the combinations of
      Spm+MeJA and EBL+MeJA can induce secondary metabolites effectively and those
      interactions play important role in the production of phytochemicals in plants.

PMID- 25053089
TI  - Quantitative study of the relationships among proteolysis, lipid oxidation,
      structure and texture throughout the dry-cured ham process.
AB  - Temperature, salt and water contents are key processing factors in dry-cured ham
      production. They affect how proteolysis, lipid oxidation, structure and texture
      evolve, and thus determine the sensory properties and final quality of dry-cured
      ham. The aim of this study was to quantify the interrelationships and the time
      course of (i) proteolysis, (ii) lipid oxidation, (iii) five textural parameters:
      hardness, fragility, cohesiveness, springiness and adhesiveness and (iv) four
      structural parameters: fibre numbers, extracellular spaces, cross section area,
      and connective tissue area, during the dry-cured ham process. Applying multiple
      polynomial regression enabled us to build phenomenological models relating
      proteolysis, salt and water contents to certain textural and structural
      parameters investigated. A linear relationship between lipid oxidation and
      proteolysis was also established. All of these models and relationships, once
      combined with salt penetration, water migration and heat transfer models, can be
      used to dynamically simulate all of these phenomena throughout dry-cured ham
      manufacturing. 

PMID- 25053090
TI  - Antioxidant capacity of betacyanins as radical scavengers for peroxyl radical and
      nitric oxide.
AB  - This study was designed to assess the antioxidant capacity of betacyanins as
      indole derived plant pigments, such as betanin, phyllocactin and betanidin. The
      antioxidant capacity of the betacyanins was evaluated as an index of radical
      scavenging ability using the peroxyl radical generating system in the presence of
      AAPH and NO generating system using NOR3 as an NO donor. The peroxyl radical
      scavenging capacity was dose-dependent in the low concentration range (25-100
      nM). The mol-Trolox equivalent activity/mol compound (mol-TEA/mol-compound) as an
      index of the antioxidant capacity indicated the following order at 10.70 +/-
      0.01, 3.31 +/- 0.14 and 2.83 +/- 0.01 mol-TEA/mol-compound for betanidin, betanin
      and phyllocactin, respectively. In addition, betacyanins reduced the nitrite
      level in the low concentration range of 2.5-20 MUM. The IC50 values (MUM) of
      nitrogen radical scavenging activity were 24.48, 17.51 and 6.81 for betanin,
      phyllocactin and betanidin. ESR studies provided evidence that the compounds
      directly scavenged NO. These results indicated that betacyanins have a strong
      antioxidant capacity, particularly betanidin with a catechol group had higher
      activity than those of the glycoside of betacyanins. This study demonstrated that
      the betacyanins will be useful as natural pigments to provide defence against
      oxidative stress.

PMID- 25053091
TI  - Development of an online-SPE-LC-MS method for the investigation of the intestinal
      absorption of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) and its
      bacterial metabolite PHIP-M1 in a Caco-2 Transwell system.
AB  - Heterocyclic aromatic amines such as PHIP are formed during the heat processing
      of food. PHIP undergoes bacterial metabolism leading to 7-hydroxy-5-methyl-3
      phenyl-6,7,8,9-tetrahydropyrido[3',2':4,5]imidazo[1,2-a]pyrimidin-5-ium chloride
      (PHIP-M1) as main metabolite. We developed an LC-MS method with automated sample
      preparation by online-solid-phase-extraction for the simultaneous quantification
      of PHIP and its mammalian and bacterial metabolites N-hydroxy-PHIP, 4-OH-PHIP and
      PHIP-M1 in biological samples. The method was used to investigate the transport
      of PHIP-M1 through a Caco-2 cell monolayer. The experiments show that PHIP-M1
      rapidly crosses the cell monolayer and that PHIP-M1 is a substrate for P
      glycoprotein and the multiple drug resistance 2 transporter. The intestinal
      absorption of PHIP-M1 is comparable with that of PHIP and a moderate to high
      bioavailability has to be expected. Thus, not only the human metabolites of PHIP
      but also the bacterial metabolite PHIP-M1 formed in the gut could contribute to
      the toxic effects of PhIP. 

PMID- 25053092
TI  - Migration of antimony from polyethylene terephthalate used in mineral water
      bottles.
AB  - The influence of storage time and temperature on Sb migration from PET bottles
      into mineral water was studied in short-term tests lasting up to 15 days and long
      term studies lasting up to 220 days. Samples purchased were stored in three
      different coloured bottles: clear (CL), light blue (LB) and dark blue (DB). Sb
      migration was assayed by HG-AFS for total determination and HPLC-ICP-MS for
      speciation analysis. Migration studies showed that waters stored at 4 and 20 
      degrees C were not subject to Sb migration. At 40  degrees C there was a
      significant increase in Sb concentration, although the maximum limit established
      by the European Union (5.0 MUgL(-)(1)) was not exceeded, whereas at 60  degrees C
      samples were subject to considerable Sb migration after 30 days of storage. In
      this case, the maximum limit established by the European Union was exceeded and
      both Sb (V) and Sb (III) were detected.

PMID- 25053093
TI  - Analysis of regioisomers of polyunsaturated triacylglycerols in marine matrices
      by HPLC/HRMS.
AB  - Natural sources of triacylglycerols containing omega-3 fatty acids are of
      particular interest due to their protective role against several human diseases.
      However, as it has been well ascertained, the position of the omega-3 fatty acid
      on the triacylglycerol backbone influences how digestion occurs. In particular,
      occurrence at the sn-2 position allows optimal intestinal absorption conditions.
      The analytical protocol for regioisomer characterisation of fatty acids in a
      triacylglycerol usually requires the use of stereospecific lipases before
      instrumental identification. In this paper, we propose a more direct instrumental
      determination of triacylglycerol composition along with sn-2 positional
      identification of the fatty acids constituents by Liquid Chromatography-High
      Resolution Mass Spectrometry. Different intensities of product signals obtained
      in MS(2) and MS(3) experiments were used to define an interpretative scheme able
      to rationalise the stereochemistry of the TAGs. Marine matrices like tuna and
      algae oils have been studied in detail, their triacylglycerols identified and sn
      2 positional arrangement of fatty acid constituents assessed. 

PMID- 25053094
TI  - Response surface methodology to optimise Accelerated Solvent Extraction of
      steviol glycosides from Stevia rebaudiana Bertoni leaves.
AB  - Following the approval of steviol glycosides as a food additive in Europe in
      December 2011, large-scale stevia cultivation will have to be developed within
      the EU. Thus there is a need to increase the efficiency of stevia evaluation
      through germplasm enhancement and agronomic improvement programs. To address the
      need for faster and reproducible sample throughput, conditions for automated
      extraction of dried stevia leaves using Accelerated Solvent Extraction were
      optimised. A response surface methodology was used to investigate the influence
      of three factors: extraction temperature, static time and cycle number on the
      stevioside and rebaudioside A extraction yields. The model showed that all the
      factors had an individual influence on the yield. Optimum extraction conditions
      were set at 100  degrees C, 4 min and 1 cycle, which yielded 91.8% +/- 3.4% of
      total extractable steviol glycosides analysed. An additional optimisation was
      achieved by reducing the grind size of the leaves giving a final yield of 100.8%
      +/- 3.3%.

PMID- 25053095
TI  - Detection of heavy metal ions in contaminated water by surface plasmon resonance
      based optical fibre sensor using conducting polymer and chitosan.
AB  - Optical fibre surface plasmon resonance (SPR) based sensor for the detection of
      heavy metal ions in the drinking water is designed. Silver (Ag) metal and indium
      tin oxide (ITO) are used for the fabrication of the SPR probe which is further
      modified with the coating of pyrrole and chitosan composite. The sensor works on
      the wavelength interrogation technique and is capable of detecting trace amounts
      of Cd(2+), Pb(2+), and Hg(2+) heavy metal ions in contaminated water. Four types
      of sensing probes are fabricated and characterised for heavy metal ions out of
      these pyrrole/chitosan/ITO/Ag coated probe is found to be highly sensitive among
      all other probes. Further, the cadmium ions bind strongly to the sensing surface
      than other ions and due to this the sensor is highly sensitive for Cd(2+) ions.
      The sensor's performance is best for the low concentrations of heavy metal ions
      and its sensitivity decreases with the increasing concentration of heavy metal
      ions. 

PMID- 25053096
TI  - Chemometric dissimilarity in nutritive value of popularly consumed Nigerian brown
      and white common beans.
AB  - Brown beans are the preferred varieties over the white beans in Nigeria due to
      their assumed richer nutrients. This study was aimed at assessing and
      characterising some popular Nigerian common beans for their nutritive value based
      on seed coat colour. Three varieties, each, of Nigerian brown and white beans,
      and one, each, of French bean and soybean were analysed for 19 nutrients. Z
      statistics test showed that Nigerian beans are nutritionally analogous to French
      bean and soybean. Analysis of variance showed that seed coat colour varied with
      proximate nutrients, Ca, Fe, and Vit C. Chemometric analysis methods revealed
      superior beans for macro and micro nutrients and presented clearer groupings
      among the beans for seed coat colour. The study estimated a moderate genetic
      distance (GD) that will facilitate transfer of useful genes and intercrossing
      among the beans. It also offers an opportunity to integrate French bean and
      soybean into genetic improvement programs in Nigerian common beans. 

PMID- 25053097
TI  - Optimization of microwave-assisted extraction of polyphenols from Myrtus communis
      L. leaves.
AB  - Phytochemicals, such as phenolic compounds, are of great interest due to their
      health-benefitting antioxidant properties and possible protection against
      inflammation, cardiovascular diseases and certain types of cancer. Maximum
      retention of these phytochemicals during extraction requires optimised process
      parameter conditions. A microwave-assisted extraction (MAE) method was
      investigated for extraction of total phenolics from Myrtus communis leaves. The
      total phenolic capacity (TPC) of leaf extracts at optimised MAE conditions was
      compared with ultrasound-assisted extraction (UAE) and conventional solvent
      extraction (CSE). The influence of extraction parameters including ethanol
      concentration, microwave power, irradiation time and solvent-to-solid ratio on
      the extraction of TPC was modeled by using a second-order regression equation.
      The optimal MAE conditions were 42% ethanol concentration, 500 W microwave power,
      62 s irradiation time and 32 mL/g solvent to material ratio. Ethanol
      concentration and liquid-to-solid ratio were the significant parameters for the
      extraction process (p<0.01). Under the MAE optimised conditions, the recovery of
      TPC was 162.49 +/- 16.95 mg gallic acidequivalent/gdry weight(DW), approximating
      the predicted content (166.13 mg GAE/g DW). When bioactive phytochemicals
      extracted from Myrtus leaves using MAE compared with UAE and CSE, it was also
      observed that tannins (32.65 +/- 0.01 mg/g), total flavonoids (5.02 +/- 0.05 mg
      QE/g) and antioxidant activities (38.20 +/- 1.08 MUg GAE/mL) in MAE extracts were
      higher than the other two extracts. These findings further illustrate that
      extraction of bioactive phytochemicals from plant materials using MAE method
      consumes less extraction solvent and saves time.

PMID- 25053098
TI  - Tryptophan-containing dipeptides are C-domain selective inhibitors of angiotensin
      converting enzyme.
AB  - Somatic angiotensin-converting enzyme (ACE) contains two active sites, the C- and
      N-domain, from which the C-domain is supposed to play a major role in blood
      pressure regulation and is therefore a promising pharmacological target to reduce
      blood pressure without side-effects. We report for the first time that tryptophan
      containing dipeptides such as Ile-Trp or Val-Trp, which were recently found in
      food protein hydrolysates, are selective and competitive inhibitors for the C
      domain with a selectivity factor of 40 and 70, respectively. Structure-activity
      studies showed that an N-terminal aliphatic amino acid and a tryptophan moiety in
      the P2' position are favourable structures for C-domain inhibition in dipeptides.
      In contrast, the lactotripeptides Ile-Pro-Pro and Val-Pro-Pro, which were widely
      used as ingredients for hypotensive food, showed a slight selectivity for the N
      domain. Hence, tryptophan containing dipeptides are interesting ingredients for
      functional foods as a natural prevention for hypertension with reduced side
      effects due to its selective inhibition of the C-domain. 

PMID- 25053099
TI  - Selenium biofortification of broccoli and carrots grown in soil amended with Se
      enriched hyperaccumulator Stanleya pinnata.
AB  - Amending soils with Se-hyperaccumulator plant derived sources of selenium (Se)
      may be useful for increasing the Se content in food crops in Se-deficient regions
      of the world. In this study we evaluated total Se and the different chemical
      species of Se in broccoli and carrots grown in soils amended with ground shoots
      of the Se-hyperaccumulator Stanleyapinnata. With increasing application rates of
      S. pinnata, total plant Se concentrations increased to nutritionally ideal levels
      inside edible parts. Selenium compounds in aqueous extracts were analyzed by SAX
      HPLC-ICPMS and identified as a variety of mainly organic-Se forms. Together with
      bulk Se K-edge X-ray absorption near-edge structure (XANES) analysis performed on
      broccoli florets, carrot roots and shoots, dried ground S. pinnata, and the
      amended soil at post-plant, we demonstrate that Se-enriched S. pinnata is
      valuable as a soil amendment for enriching broccoli and carrots with healthful
      forms of organic-Se. 

PMID- 25053100
TI  - Trilobatin attenuates the LPS-mediated inflammatory response by suppressing the
      NF-kappaB signaling pathway.
AB  - We investigated the anti-inflammatory effect of trilobatin, the flavonoid
      isolated from the leaves of Lithocarpus polystachyus Rehd, as well as the
      underlying molecular mechanisms. Treatment with trilobatin (0.005-5 MUM) dose
      dependently inhibited the lipopolysaccharide (LPS)-induced mRNA expression and
      secretion of pro-inflammatory cytokines, including tumor necrosis factor alpha
      (TNFalpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), in RAW 264.7
      macrophages. However, no further inhibition was detected when the concentration
      of trilobatin was increased to 50 MUM. Western blot analysis confirmed that the
      mechanism of the anti-inflammatory effect was correlated with the inhibition of
      LPS-induced inhibitor of nuclear factor-kappa B alpha (IkappaBalpha) degradation
      and nuclear factor-kappa B (NF-kappaB) p65 phosphorylation. In addition,
      trilobatin also showed a significant inhibition of LPS-induced TNFalpha and IL-6
      at both the mRNA and protein levels in a mouse model. Our results suggest that
      trilobatin potentially inhibits the LPS-induced inflammatory response by
      suppressing the NF-kappaB signaling pathway.

PMID- 25053101
TI  - Sorbitol, Rubus fruit, and misconception.
AB  - It is unclear how the misunderstanding that Rubus fruits (e.g., blackberries,
      raspberries) are high in sugar alcohol began, or when it started circulating in
      the United States. In reality, they contain little sugar alcohol. Numerous
      research groups have reported zero detectable amounts of sugar alcohol in fully
      ripe Rubus fruit, with the exception of three out of 82 Rubus fruit samples
      (cloudberry 0.01 g/100 g, red raspberry 0.03 g/100 g, and blackberry 4.8 g/100
      g(*); (*)highly unusual as 73 other blackberry samples contained no detectable
      sorbitol). Past findings on simple carbohydrate composition of Rubus fruit, other
      commonly consumed Rosaceae fruit, and additional fruits (24 genera and species)
      are summarised. We are hopeful that this review will clarify Rosaceae fruit sugar
      alcohol concentrations and individual sugar composition; examples of non-Rosaceae
      fruit and prepared foods containing sugar alcohol are included for comparison. A
      brief summary of sugar alcohol and health will also be presented.

PMID- 25053102
TI  - Selection and characterization of DNA aptamers against Staphylococcus aureus
      enterotoxin C1.
AB  - Enterotoxins from pathogenic bacteria are known as the main reason that can cause
      the bacterial foodborne diseases. In this study, aptamers that bound to
      Staphylococcus aureus enterotoxin C1 (SEC1) with high affinity and selectivity
      were generated in vitro by twelve rounds of selection based on magnetic
      separation technology, with a low-level dissociation constant (Kd) value of 65.14
      +/- 11.64 nmol/L of aptamer C10. Aptamer-based quantification of SEC1 in the food
      sample by a graphene oxide (GO)-based method was implemented to investigate the
      potential of the aptamer against SEC1 with a limit of detection of 6 ng/mL. On
      the basis of this work, biosensors using the selected SEC1 aptamers as new
      molecular recognition elements could be applied for innovative determinations of
      SEC1.

PMID- 25053103
TI  - Ultra-high performance liquid chromatographic and mass spectrometric analysis of
      active vitamin B12 in cells of Propionibacterium and fermented cereal matrices.
AB  - A sensitive and selective method is needed to analyse in situ produced vitamin
      B12 in plant-based materials, potential new dietary sources of vitamin B12. A
      UHPLC/UV method was developed and validated for the determination of human active
      vitamin B12 in cell extracts of Propionibacterium freudenreichii subsp. shermanii
      and after immunoaffinity purification in extracts of cereal matrices fermented by
      P. freudenreichii. An Acquity HSS T3 C18 column resulted in a baseline
      separation, a calibration curve of excellent linearity and a low limit of
      detection (0.075 ng/5 MUL injection). As confirmed by UHPLC-MS, the active
      vitamin B12 could be separated from pseudovitamin B12. The recovery of vitamin
      B12 from purified spiked cereal matrices was good (>90%; RSD<5%). A nutritionally
      relevant amount of active vitamin B12 was produced by P. freudenreichii in cereal
      malt matrices (up to 1.9 MUg/100 g) in 24h at 28  degrees C.

PMID- 25053104
TI  - Non-rhabdoid pediatric SMARCB1-deficient tumors: overlap between chordomas and
      malignant rhabdoid tumors?
AB  - Somatic alterations in the tumor suppressor gene SMARCB1 were first described in
      the malignant rhabdoid tumor (MRT) of infancy. Since then, SMARCB1 alterations
      have been found in other tumors, forming a varied group of SMARCB1-deficient
      tumors, which sometimes shares overlapping immunohistochemical and histological
      findings. Thus, the diagnosis is challenging. We report two cases of pediatric
      SMARCB1-deficient tumors from the clivus that illustrate the diagnostic
      difficulties. Both cases were strongly positive for epithelial markers associated
      with loss of BAF47 (INI1) expression, and were negative for S100 and CD34.
      Molecular analyses of the SMARCB1 gene found a deletion of all nine exons in both
      cases. In the first case, a 5-year-old girl presented with a thoracic metastasis
      of a clival tumor, which was diagnosed as MRT and treated accordingly. The
      morphological findings and the expression of brachyury would favor the diagnosis
      of a poorly differentiated chordoma. The second case was a quickly fatal clival
      tumor in a 2-year-old boy: This tumor was morphologically undifferentiated and
      raises the problem of differential diagnosis between an MRT, a malignant
      myoepithelial tumor, or an undifferentiated chordoma due to the location and the
      expression of brachyury. Studies of biological signatures, such as transcriptome
      profiling, could help to understand the apparent overlap between these tumors. 

PMID- 25053105
TI  - High animal fat intake enhances prostate cancer progression and reduces
      glutathione peroxidase 3 expression in early stages of TRAMP mice.
AB  - BACKGROUND: Prostate cancer is the most frequently diagnosed cancer in Western
      men, and more men have been diagnosed at younger ages in recent years. A high-fat
      Western-style diet is a known risk factor for prostate cancer and increases
      oxidative stress. METHODS: We evaluated the association between dietary animal
      fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3
      (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate
      (TRAMP) mice. Six-week-old male nontransgenic and TRAMP mice were placed on high
      animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5
      or 10 weeks. RESULTS: The histopathological score increased with age and high-fat
      diet consumption. The histopathological scores in dorsal and lateral lobes
      increased in the 10-week high-fat diet group (6.2+/-0.2 and 6.2+/-0.4,
      respectively) versus the 10-week control diet group (5.3+/-0.3 and 5.2+/-0.2,
      respectively). GPx3 decreased both at the mRNA and protein levels in mouse
      prostate. GPx3 mRNA expression decreased (~36.27% and ~23.91%, respectively) in
      the anterior and dorsolateral prostate of TRAMP mice fed a high-fat diet compared
      to TRAMP mice fed a control diet. Cholesterol treatment increased PC-3 human
      prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and
      increased H2 O2 levels in culture medium. Moreover, increasing GPx3 mRNA
      expression by troglitazone in PC-3 cells decreased cell proliferation and lowered
      H2 O2 levels. CONCLUSIONS: Dietary fat enhances prostate cancer progression,
      possibly by suppressing GPx3 expression and increasing proliferation of prostate
      intraepithelial neoplasia (PIN) epithelial cells.

PMID- 25053106
TI  - The Relation of Familiarity With Sexual Abusers to Subsequent Developmental
      Adaptation in Youths Who Have Sexually Offended.
AB  - The present study explored the effects of child sexual abuse (CSA) on the
      adaptation of male juveniles who subsequently sexually offended (JSOs; n = 178;
      age, M = 16.05 years, SD = 0.27, range = 12-22). It examined multiple levels of
      interpersonal closeness between the perpetrators of sexual abuse and their JSO
      victims. JSOs who were sexually abused by older children or adults who
      cohabitated with them for at least 3 months reported higher levels of emotional
      dysregulation, callousness/manipulativeness, and sexualization than did both JSOs
      who were sexually abused by someone they had never lived with and JSOs who
      reported no experiences of sexual abuse. Implications of these findings are
      discussed. 

PMID- 25053107
TI  - Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin
      chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by
      lactoferrin.
AB  - Streptococcus pneumoniae (pneumococcus) is responsible for nearly one million
      child deaths annually. Pneumococcus causes infections such as pneumonia, otitis
      media, meningitis, and sepsis. The human immune system includes antibacterial
      peptides and proteins such as lactoferrin (LF), but its activity against
      pneumococcus is not fully understood. The aim of this work was to evaluate the
      bactericidal effect of bovine lactoferrin (bLF) and the synthetic LF-peptides
      lactoferricin (LFcin17-30), lactoferrampin (LFampin265-284), and LFchimera
      against S. pneumoniae planktonic cells. The mechanism of damage was also
      investigated, as well as the impact of these peptides on the transcription levels
      of genes known to encode important virulence factors. S. pneumoniae planktonic
      cells were treated with bLF, LFcin17-30, LFampin265-284 and LFchimera at
      different time points. The viability of treated planktonic cells was assessed by
      dilution and plating (in CFU/ml). The interaction between LF and LF-peptides
      coupled to fluorescein was visualized using a confocal microscope and flow
      cytometry, whereas the damage at structural levels was observed by electron
      microscopy. Damage to bacterial membranes was further evaluated by membrane
      permeabilization by use of propidium iodide and flow cytometry, and finally, the
      expression of pneumococcal genes was evaluated by qRT-PCR. bLF and LFchimera were
      the best bactericidal agents. bLF and peptides interacted with bacteria causing
      changes in the shape and size of the cell and membrane permeabilization.
      Moreover, the luxS gene was down-regulated in bacteria treated with LF. In
      conclusion, LF and LFchimera have a bactericidal effect, and LF down-regulates
      genes involved in the pathogenicity of pneumococcus, thus demonstrating potential
      as new agents for the treatment of pneumococcal infections. 

PMID- 25053108
TI  - Mucin 1 (MUC1) signalling contributes to increase the resistance to cell death in
      human bronchial epithelial cells exposed to nickel acetate.
AB  - We have previously reported that nickel acetate (Ni(2+)), a well-known human
      carcinogenic agents, differentially affected apoptosis in two different airway
      epithelial cell lines derived from the human respiratory tract (A549 and Beas-2B,
      respectively), suggesting a potential involvement of epidermal growth factor
      receptor (EGFR)/Neu receptors in mediating this effect. Since ErbBs are closely
      associated to Mucin 1 (MUC1), a glycoprotein component of airway mucus that is
      overexpressed in lung tumors, we have investigated the role of this signaling
      system in the survival response of airway epithelial cells against Ni(2+)-induced
      cell death. We found that A549 cells exposed to Ni(2+) do not show any
      significant increase of MUC1 levels. Conversely, Beas-2B cells exposed to
      equivalent concentrations of Ni(2+) showed increased expression of MUC1 levels
      and this correlated with increased phosphorylation of both EGFR and of the
      extracellular-regulated kinase 1/2 (ERK1/2) and increase resistance to apoptosis,
      as indicated by cell viability assessments and DNA damage. Interestingly,
      suppression of MUC1 by small interfering RNA inhibited the EGFR activation in
      Beas-2B cells, leading to a significant decrease of survival and enhancement of
      DNA fragmentation and cleaved Caspase-3 expression. These results strongly
      suggest a role for MUC1 in Ni(2+)-induced neoplastic transformation, which likely
      involves the activation of the EGFR-mediated cell survival pathway, highlighting
      new avenues in the molecular approach to lung cancer prevention. 

PMID- 25053109
TI  - Platelet-activating factor mediates the cytotoxicity induced by W7FW14F
      apomyoglobin amyloid aggregates in neuroblastoma cells.
AB  - W7FW14F apomyoglobin (W7FW14F ApoMb) amyloid aggregates induce cytotoxicity in SH
      SY5Y human neuroblastoma cells through a mechanism not fully elucidated. Amyloid
      neurotoxicity process involves calcium dyshomeostasis and reactive oxygen species
      (ROS) production. Another key mediator of the amyloid neurotoxicity is Platelet
      Activating Factor (PAF), an inflammatory phospholipid implicated in
      neurodegenerative diseases. Here, with the aim at evaluating the possible
      involvement of PAF signaling in the W7FW14F ApoMb-induced cytotoxicity, we show
      that the presence of CV3899, a PAF receptor (PAF-R) antagonist, prevented the
      detrimental effect of W7FW14F ApoMb aggregates on SH-SY5Y cell viability.
      Noticeably, we found that the activation of PAF signaling, following treatment
      with W7FW14F ApoMb, involves a decreased expression of the PAF acetylhydroase II
      (PAF-AH II). Interestingly, the reduced PAF-AH II expression was associated with
      a decreased acetylhydrolase (AH) activity and to an increased sphingosine
      transacetylase activity (TA(S)) with production of N-acetylsphingosine (C2
      ceramide), a well known mediator of neuronal caspase-dependent apoptosis. These
      findings suggest that an altered PAF catabolism takes part to the molecular
      events leading to W7FW14F ApoMb amyloid aggregates-induced cell death.

PMID- 25053110
TI  - Are Barbie and Ken too cool for school? A case-control study on the relation
      between gender and dropout.
AB  - BACKGROUND: As school dropout is an important public health problem that needs to
      be addressed, we set out to examine whether and how, beyond the well-known
      effects of sex, gender beliefs and self-reported masculinity and femininity are
      related to school dropout. METHODS: The study used a case-control design,
      consisting of 330 dropout cases and 330 controls still attending school. The
      respondents, aged between 18 and 23 years, living in the south-east of the
      Netherlands, were sent a self-administered questionnaire. Separate logistic
      regression analyses for the male and female participants were used to explore the
      relation between dropout and gender, controlling for sociodemographic
      determinants. RESULTS: As indicated by significant curvilinearity, young women
      were less likely to drop out when they occupied an intermediate positions on the
      gender variables. Odds of dropout were elevated among highly masculine women
      (odds ratio = 2.1, 95% confidence interval: 1.1-4.1), and, as indicated by
      significant interactions, also among highly masculine men with strong normative
      masculine beliefs and in feminine men who simultaneously considered themselves
      low on masculinity. CONCLUSIONS: Beyond sex, gender is important in the
      explanation of school dropout. To prevent dropout, public health professionals
      should assess, monitor and intervene on the basis of gender characteristics.

PMID- 25053111
TI  - Lithium chloride suppresses LPS-mediated matrix metalloproteinase-9 expression in
      macrophages through phosphorylation of GSK-3beta.
AB  - Abnormal degradation of matrix components due to dysregulated expression of
      matrix metalloproteinase (MMP)-9 in macrophages has been linked to progression of
      acute cerebral ischemia and atherosclerosis. We report that lithium chloride
      (LiCl) or CHIR99021, inhibitors of Wnt signaling pathway, enhance phosphorylation
      of glycogen synthase kinase-3beta and suppress lipopolysaccharide-mediated
      upregulation of MMP-9 expression in murine macrophage RAW264.7 cells in a dose
      dependent manner. Suppression of MMP-9 expression by LiCl or CHIR99021 did not
      result after inhibition of kinases involved in NFkappaB or AP-1 family proteins,
      but from changes in the activity of histone deacetylases. Beneficial effects on
      atherosclerosis or cerebral ischemia in animal studies caused by LiCl may be in
      part explained by the suppression of MMP-9 gene expression. 

PMID- 25053112
TI  - Comparison of cell number, viability, phenotypic profile, clonogenic, and
      proliferative potential of adipose-derived stem cell populations between
      centrifuged and noncentrifuged fat.
AB  - BACKGROUND: Autologous fat grafting is a widely adopted surgical technique in
      both the reconstructive and aesthetic fields. This study aimed to compare
      centrifuged lipoaspirates harvested and refined by the Coleman technique with
      noncentrifuged lipoaspirates in terms of cell number and viability, phenotypic
      profile, and clonogenic and proliferative potential of adipose-derived stem cell
      (ADSC) populations. METHODS: For each patient, both a centrifuged sample using
      the Coleman's technique and a noncentrifuged sample of adipose tissue were
      collected. Adipose-derived stem cells from both the centrifuged fraction (CF) and
      the noncentrifuged fraction (NCF) were isolated. The recovered ADSCs were used to
      set up flow cytometry analysis, colony-forming units-fibroblast (CFU-F) assays,
      and ADSC cultures. RESULTS: The number of recovered cells was variable among the
      different donors but significantly higher in the CF donors. Cell viability,
      determined by the Trypan Blue dye assay, always exceeded 95 %, in both the CF and
      NCF fractions. Analysis of the putative ADSC subpopulations showed a significant
      enrichment of the mesenchymal and endothelial progenitors in CF compared with
      NCF. No differences in the clonogenic efficiency of the ADSC samples were
      observed when the same number of cells were plated from each fraction. On the
      contrary, when equal fat volumes were compared, the colony-forming ability of CF
      was always significantly higher than that of its NCF counterparts. CONCLUSIONS:
      This is the first study to comprehensively characterize the impact of Coleman's
      technique on the quality of lipoaspirates, showing that centrifugation is safe
      and feasible and does not impair cell viability, can augment the content in ADSC
      and the frequency of CFU-F, and reduces the number of proinflammatory blood
      cells.

PMID- 25053113
TI  - Spontaneous mesenteric hematoma: a diagnostic challenge.

PMID- 25053114
TI  - Determinants of suicidal ideation and suicide attempts: parallel cross-sectional
      analyses examining geographical location.
AB  - BACKGROUND: Suicide death rates in Australia are higher in rural than urban
      communities however the contributors to this difference remain unclear.
      Geographical differences in suicidal ideation and attempts were explored using
      two datasets encompassing urban and rural community residents to examine
      associations between socioeconomic, demographic and mental health factors.
      Differing patterns of association between psychiatric disorder and suicidal
      ideation and attempts as geographical remoteness increased were investigated.
      METHODS: Parallel cross-sectional analyses were undertaken using data from the
      2007 National Survey of Mental Health and Wellbeing (2007-NSMHWB, n = 8,463),
      under-representative of remote and very remote residents, and selected
      participants from the Australian Rural Mental Health Study (ARMHS, n = 634), over
      representative of remote and very remote residents. Uniform measures of suicidal
      ideation and attempts and mental disorder using the World Mental Health Composite
      International Diagnostic Interview (WMH-CIDI-3.0) were used in both datasets.
      Geographic region was classified into major cities, inner regional and other. A
      series of logistic regressions were undertaken for the outcomes of 12-month and
      lifetime suicidal ideation and lifetime suicide attempts, adjusting for age,
      gender and psychological distress. A sub-analysis of the ARMHS sample was
      undertaken with additional variables not available in the 2007-NSMHWB dataset.
      RESULTS: Rates and determinants of suicidal ideation and suicide attempts across
      geographical region were similar. Psychiatric disorder was the main determinant
      of 12-month and lifetime suicidal ideation and lifetime suicide attempts across
      all geographical regions. For lifetime suicidal ideation and attempts, marital
      status, employment status, perceived financial adversity and mental health
      service use were also important determinants. In the ARMHS sub-analysis, higher
      optimism and better perceived infrastructure and service accessibility tended to
      be associated with a lower likelihood of lifetime suicidal ideation, when age,
      gender, psychological distress, marital status and mental health service use were
      taken into account. CONCLUSIONS: Rates and determinants of suicidal ideation and
      attempts did not differ according to geographical location. Psychiatric disorder,
      current distress, employment and financial adversity remain important factors
      associated with suicidal ideation and attempts across all regions in Australia.
      Regional characteristics that influence availability of services and lower
      personal optimism may also be associated with suicidal ideation in rural
      communities.

PMID- 25053115
TI  - The effects of time, temperature, and pH on the stability of PDU bacterial
      microcompartments.
AB  - Bacterial microcompartments (MCPs) are subcellular organelles that are composed
      of a protein shell and encapsulated metabolic enzymes. It has been suggested that
      MCPs can be engineered to encapsulate protein cargo for use as in vivo
      nanobioreactors or carriers for drug delivery. Understanding the stability of the
      MCP shell is critical for such applications. Here, we investigate the integrity
      of the propanediol utilization (Pdu) MCP shell of Salmonella enterica over time,
      in buffers with various pH, and at elevated temperatures. The results show that
      MCPs are remarkably stable. When stored at 4 degrees C or at room temperature,
      Pdu MCPs retain their structure for several days, both in vivo and in vitro.
      Furthermore, Pdu MCPs can tolerate temperatures up to 60 degrees C without
      apparent structural degradation. MCPs are, however, sensitive to pH and require
      conditions between pH 6 and pH 10. In nonoptimal conditions, MCPs form
      aggregates. However, within the aggregated protein mass, MCPs often retain their
      polyhedral outlines. These results show that MCPs are highly robust, making them
      suitable for a wide range of applications.

PMID- 25053116
TI  - Cardiac implantable electronic device infections: facts, current practice, and
      the unanswered questions.
AB  - Over the last 2 decades, there has been a surge in newly implanted cardiac
      implantable electronic devices (CIEDs). This is largely due to the increasing
      indications for these devices and their role in improving both survival and
      quality of life among certain groups of patients with heart disease. However, the
      net benefit of these devices is affected by adverse events and complications.
      CIED infection is one of these complications that increase morbidity and
      mortality. Patients with CIED infection can present with pocket infection or
      endovascular infection. Management usually involves CIED removal and antibiotic
      therapy. Despite its importance, many questions remain unanswered. Longitudinal
      studies and randomized clinical trials are needed to better define risk factors
      for CIED infections and outcomes and to help assess best practices to prevent
      this complication. 

PMID- 25053117
TI  - Contralateral dissociation between neural activity and cerebral blood volume
      during recurrent acute focal neocortical seizures.
AB  - OBJECTIVE: Whether epileptic events disrupt normal neurovascular coupling
      mechanisms locally or remotely is unclear. We sought to investigate neurovascular
      coupling in an acute model of focal neocortical epilepsy, both within the seizure
      onset zone and in contralateral homotopic cortex. METHODS: Neurovascular coupling
      in both ipsilateral and contralateral vibrissal cortices of the urethane
      anesthetized rat were examined during recurrent 4-aminopyridine (4-AP, 15 mm, 1
      MUl) induced focal seizures. Local field potential (LFP) and multiunit spiking
      activity (MUA) were recorded via two bilaterally implanted 16-channel
      microelectrodes. Concurrent two-dimensional optical imaging spectroscopy was used
      to produce spatiotemporal maps of cerebral blood volume (CBV). RESULTS: Recurrent
      acute seizures in right vibrissal cortex (RVC) produced robust ipsilateral
      increases in LFP and MUA activity, most prominently in layer 5, that were
      nonlinearly correlated to local increases in CBV. In contrast, contralateral left
      vibrissal cortex (LVC) exhibited relatively smaller nonlaminar specific increases
      in neural activity coupled with a decrease in CBV, suggestive of dissociation
      between neural and hemodynamic responses. SIGNIFICANCE: These findings provide
      insights into the impact of epileptic events on the neurovascular unit, and have
      important implications both for the interpretation of perfusion-based imaging
      signals in the disorder and understanding the widespread effects of epilepsy. A
      PowerPoint slide summarizing this article is available for download in the
      Supporting Information section here.

PMID- 25053118
TI  - Major histocompatibility complex class II polymorphisms in forest musk deer
      (Moschus berezovskii) and their probable association with purulent disease.
AB  - Genes of the major histocompatibility complex (MHC) family are crucial in immune
      responses because they present pathogenic peptides to T cells. In this study, we
      analysed the genetic variation in forest musk deer (Moschus berezovskii) MHC II
      genes and its potential association with musk deer purulent disease. In total, 53
      purulent disease-susceptible and 46 purulent disease-resistant individuals were
      selected for MHC II exon 2 fragment analysis. Among them, 16 DQ alleles and four
      additional DR alleles were identified, with DQ exon 2 fragments displaying a low
      level of polymorphism. The nonsynonymous substitutions exceeded the synonymous
      substitutions in the peptide-binding sites of DQA2, DQB1 and DQB2. Then, 28 MHC
      II alleles were used to analyse the distribution patterns of purulent disease
      between the susceptible and resistant groups. Among them, three alleles (DQA1*01,
      DQA1*02 and DQA2*04) were found to be resistant, and five alleles (DRB3*07,
      DQA1*03, DQA1*04, DQA2*05 and DQA2*06) were found to increase susceptibility.
      Additionally, three haplotypes were found to be putatively associated with musk
      deer purulent disease. However, these three haplotypes were only found in the
      resistant or susceptible group, and their frequencies were low. The results from
      our study support a contributory role of MHC II polymorphisms in the development
      of purulent disease in forest musk deer. 

PMID- 25053119
TI  - Pulmonary overexpression of inhibitor kappaBalpha decreases the severity of
      ventilator-induced lung injury in a rat model.
AB  - BACKGROUND: Activation of the nuclear factor-kappaB (NF-kappaB) pathway is
      central to the pathogenesis of lung injury and inflammation. We determined
      whether targeted overexpression of inhibitor-kappaBalpha (IkappaBalpha) in the
      lung could decrease the severity of ventilator-induced lung injury (VILI).
      METHODS: Anaesthetized adult male Sprague-Dawley rats were randomly allocated to
      undergo intratracheal instillation of: (i) vehicle alone (surfactant, n=10); (ii)
      1*10(10) adeno-associated virus encoding IkappaBalpha (AAV-IkappaBalpha, n=10);
      (iii) 5*10(10) AAV-IkappaBalpha (n=10); and (iv) 1*10(10) AAV-Null (n=5). This
      was followed by 4 h of injurious mechanical ventilation. Subsequent experiments
      examined the effect of IkappaBalpha overexpression in animals undergoing
      'protective' mechanical ventilation. RESULTS: IkappaBalpha overexpression
      increased survival duration at both the lower [3.8 h (0.4)] and higher [3.6 h
      (0.7)] doses compared with vehicle [2.7 h (1.0)] or the null transgene [2.2 h
      (0.8)]. IkappaBalpha overexpression reduced the alveolar-arterial oxygen gradient
      (kPa) at both the lower [53 (21)] and higher [52 (19)] doses compared with
      vehicle [75 (8.5)] or the null transgene [70 (15)], decreased alveolar neutrophil
      infiltration, and reduced alveolar concentrations of interleukin (IL)-1beta and
      IL-10. The lower IkappaBalpha dose was as effective as the higher dose.
      IkappaBalpha overexpression had no effect in the setting of protective lung
      ventilation. CONCLUSIONS: Inhibition of pulmonary NF-kappaB activity by
      IkappaBalpha overexpression reduced the severity of VILI in a rat model.

PMID- 25053121
TI  - Construction of polyelectrolyte-responsive microgels, and polyelectrolyte
      concentration and chain length-dependent adsorption kinetics.
AB  - We report on the construction of a polyelectrolyte-responsive system evolved from
      sterically stabilized protonated poly(2-vinylpyridine) (P2VPH(+)) microgels.
      Negatively charged sodium dodecylbenzenesulfonate (SDBS) surfactants could be
      readily internalized into the cationic microgels by means of electrostatic
      interactions, resulting in microgel collapse and concomitant formation of
      surfactant micellar domains (P2VPH(+)/SDBS)-contained electrostatic complexes.
      These internal hydrophobic domains conferred the opportunity of fluorescent dyes
      to be loaded. The obtained fluorescent microgel complexes could be further
      disintegrated in the presence of anionic polyelectrolyte, poly(sodium 4
      styrenesulfonate) (PNaStS). The stronger electrostatic attraction between
      multivalent P2VPH(+) microgels and PNaStS polyelectrolyte than single-charged
      surfactant led to triggered release of the encapsulated pyrene dyes from the
      hydrophobic interiors into microgel dispersion. The process was confirmed by
      laser light scattering (LLS) and fluorescence measurements. Furthermore, the
      entire dynamic process of PNaStS adsorption into P2VPH(+) microgel interior was
      further studied by stopped-flow equipment as a function of polyelectrolyte
      concentration and degree of polymerization. The whole adsorption process could be
      well fitted with a double-exponential function, suggesting a fast (tau1) and a
      slow (tau2) relaxation time, respectively. The fast process (tau1) was correlated
      well with the approaching of PNaStS with P2VPH(+) microgel to form a
      nonequilibrium complex within the microgel shell, while the slow process (tau2)
      was consistent with the formation of equilibrium complexes in the microgel deeper
      inside. This simple yet feasible design augurs well for the promising
      applications in controlled release fields. 

PMID- 25053120
TI  - [Is it acceptable in 2014 that three-quarters of newborns are intubated without
      any sedation in the delivery room?].

PMID- 25053122
TI  - Effort-Reward Imbalance and Mental Health Problems in 1074 German Teachers,
      Compared with Those in the General Population.
AB  - High degrees of premature retirement among teachers warrant investigating the
      occupational burden and the mental health status of this profession. A sample of
      1074 German teachers participated in this study. Two samples of the general
      population (N = 824 and N = 792) were used as comparison groups. Work distress
      was assessed with the Effort-Reward-Imbalance questionnaire, and mental health
      problems were measured with the General Health Questionnaire (GHQ-12). Teachers
      reported more effort-reward imbalance (M = 0.64) compared with the general
      population (M = 0.57), and they perceived more mental health problems (GHQ: M =
      12.1) than the comparison group (M = 9.5). School type was not associated with
      work stress and mental health. Teachers with leading functions perceived high
      degrees of effort and reward, resulting in a moderate effort-reward ratio and no
      heightened mental health problems. Teachers working full time reported more
      effort than teachers working part time, but the reward mean values of both groups
      were similar. This results in a somewhat unfavourable effort-reward ratio of
      teachers working full time. Moreover, teachers working full time reported more
      mental health problems. The results support the appropriateness of the effort
      reward conception, applied to the profession of teachers. The higher degree of
      effort-reward imbalance and the level of mental health problems warrant
      preventive measures. Copyright (c) 2014 John Wiley & Sons, Ltd. 

PMID- 25053123
TI  - Pain perception in female adolescents with borderline personality disorder.
AB  - Borderline personality disorder (BPD) is a severe and often debilitating
      psychiatric disorder that begins during adolescence. Core features of BPD are
      affective dysregulation, dysfunctional self-concepts, and difficulties in social
      interactive domains. A widely accepted marker for severe emotion dysregulation in
      adult BPD is decreased pain sensitivity. Until now it is unclear whether this
      characteristic feature of BPD is already present during adolescence. Thus, this
      study aims to investigate pain sensitivity in adolescent patients meeting DSM-IV
      criteria for BPD. 20 female adolescent patients with BPD (mean age 16.4 years)
      and 20 healthy age-matched control participants were investigated. Detection and
      pain thresholds for thermal stimuli were assessed on both hands. Furthermore,
      self-rating instruments were used to assess overall psychopathology,
      dissociation, and depression. We found significantly higher pain thresholds in
      patients with BPD than in healthy controls. Patients with BPD had higher
      intensities of depression, overall psychopathology, and dissociative symptoms,
      but there was no correlation between pain sensitivity and any of these measures
      of psychopathology. These findings are in line with previous findings in adult
      BPD patients concerning lower pain sensitivity as compared to healthy controls.
      This provides support for the idea that disturbed pain processing is not only a
      consequence of chronic BPD but is already present in early stages of BPD. 

PMID- 25053124
TI  - Maternal pre-pregnancy risk drinking and toddler behavior problems: the Norwegian
      Mother and Child Cohort Study.
AB  - Maternal risk drinking may be a risk factor for child behavior problems even if
      the mother has discontinued this behavior. Whether pre-pregnancy risk drinking is
      an independent predictor of child behavior problems, or whether a potential
      effect may be explained by maternal alcohol use during and after pregnancy or
      other adverse maternal characteristics, is not known. Employing data from the
      Norwegian Mother and Child Cohort Study (MoBa), longitudinal associations between
      maternal pre-pregnancy risk drinking and behavior problems in toddlers aged 18
      and 36 months were examined. Included in the study was mothers answering MoBa
      questionnaires when the child was 18 (N = 56,682) and 36 months (N = 46,756), and
      who had responded to questions regarding pre-pregnancy risk drinking at gestation
      week 17/18, using the screening instrument T-ACE. Toddler behavior problems were
      measured with items from Child Behavior Checklist. Associations were analyzed
      with multivariate logistic regression, controlling for pre and postnatal alcohol
      use, as well as other relevant covariates. Pre-pregnancy risk drinking was
      associated with child behavior problems at 18 and 36 months, even after
      controlling for pre and postnatal alcohol use. Maternal ADHD and anxiety and
      depression were the only covariates that had any substantial impact on the
      associations. When all covariates were included in the model, the associations
      were weak for internalizing behavior problems and non-significant for
      externalizing behavior problems. Pre-pregnancy risk drinking may predict early
      development of behavior problems in the offspring. This increased risk may be due
      to other adverse maternal characteristics associated with risk drinking, in
      particular co-occurring maternal psychopathology. 

PMID- 25053125
TI  - PAIN--perception and assessment of painful procedures in the NICU.
AB  - This prospective cross-sectional study was undertaken to determine the frequency
      of procedural pain among 101 neonates in the first 14 days of admission to a
      neonatal intensive care unit (NICU) in South India and to study the perception of
      health-care professionals (HCP) about newborn procedural pain. The total number
      of painful procedures was 8.09 +/- 5.53 per baby per day and 68.32 +/- 64.78 per
      baby during hospital stay. The most common procedure was heel prick (30%). The
      HCP were administered a questionnaire to assess their perception of pain for
      various procedures. Procedures were perceived as more painful by nurses than by
      doctors. Chest tube placements and lumbar puncture were considered most painful.
      This study shows that the neonates in the NICU in developing countries experience
      many painful procedures. The awareness about this intensity of pain should
      provide a valuable tool in formulating pain-reduction protocols for management in
      low resource settings. 

PMID- 25053126
TI  - Holding and restraining children for clinical procedures within an acute care
      setting: an ethical consideration of the evidence.
AB  - This critical reflection on the ethical concerns of current practice is
      underpinned by a systematic synthesis of current evidence focusing on why and how
      children are held or restrained for clinical procedures within acute care and the
      experiences of those present when a child is held against their wishes. Empirical
      evidence from a range of clinical settings internationally demonstrates that
      frequently children are held for procedures to be completed; younger children and
      those requiring procedures perceived as urgent are more likely to be held.
      Parents and health professionals express how holding children for procedures can
      cause feelings of moral distress expressed as uncertainty, guilt and upset and
      that this act breaches the trusting and protective relationship established with
      children. Despite this, children's rights and alternatives to holding are not
      always respected or explored. Children's experiences and perceptions are absent
      from current literature. Children and young people have a moral right to have
      their voice and protests heard and respected and for these to inform judgements
      of their best interests and the actions of health professionals. Without robust
      evidence, debate and recognition that children are frequently held against their
      wishes in clinical practice for procedures which may not be urgent, children's
      rights will continue to be compromised. 

PMID- 25053127
TI  - Current challenges in QSAR/QSPR analysis.

PMID- 25053128
TI  - The structural origin of the unusual compression behaviors in nanostructured
      TiO2: insights from first-principles calculations.
AB  - First-principles calculations of anatase structured TiO2 and ZrO2 as well as of
      TiO2-B were carried up to 20 GPa in order to develop an understanding of the
      unusual compression and pressure-dependent phase transitions reported for
      nanocrystalline (nc) pure and Zr-doped anatase and nc TiO2-B. The computations,
      carried out using two global hybrid density functional-Hartree-Fock formulations
      and all-electron basis sets, reveal sharp lattice hardening along the
      crystallographic a direction and concurrent lattice softening along c for anatase
      TiO2 at 10-12 GPa, and smooth anisotropic compression for ZrO2 anatase.
      Significant structural changes beginning at ~10 GPa are also predicted for TiO2
      B, most dramatically shown by the pressure-dependent change in the monoclinic
      angle beta. These structural changes, resulting from intrinsic crystal structure
      destabilization under extended pressure metastability, have been suggested as
      being responsible for the unusual mechanical behaviors reported for pure and Zr
      doped nanocrystalline and microcrystalline anatase TiO2 and nc TiO2-B. 

PMID- 25053130
TI  - Two-port cholecystectomy maintains safety and feasibility in benign gallbladder
      diseases: a comparative study.
AB  - PURPOSE: In an effort to overcome the limitations of single-port laparoscopic
      cholecystectomy (LC) while preserving the cosmetic benefits of reduced ports
      cholecystectomy, we have developed a 2-port LC that allows for the full,
      unrestricted use of 4 laparoscopic instruments. METHODS: We retrospectively
      analyzed data of patients who had undergone either 4-port LC or 2-port LC for
      benign gallbladder diseases between March 2007 and March 2013. Two incisions of 2
      port LC were composed of an umbilical incision as the manner of single-port
      laparoscopic surgery and a 5-mm epigastric incision. These two incisions were
      utilized for comfortable bimanual manipulation under the liver-elevated vision
      provided by a liver retractor. RESULTS: During the study period, 766 patients
      underwent LC; 263 (34.3%) started with 4-port LC, and 503 (65.7%) started with 2
      port LC. Of patients started with 2-port LC, 486 patients (96.6%) was ended up
      with 2-port without open conversion or addition of port(s). The two groups had
      similar operative time, open conversion rate, incidence of complications,
      analgesic requirement, and length of postoperative hospital stay. Multivariate
      analyses revealed that the independent factors related to prolonged operative
      time (>= 90 th percentile) in 2-port LC were the presence of cholecystitis (odds
      ratio [OR] 2.412, 95% CI 1.246-4.668, p = 0.009) and admission through the
      emergency department (OR 2.132, 95% CI 1.135-4.004, p = 0.019). CONCLUSION: This
      study suggests that 2-port LC for benign gallbladder diseases is as safe and
      feasible as 4-port LC when it is performed by surgeons trained in conventional
      laparoscopic techniques.

PMID- 25053129
TI  - Vaccination with autologous dendritic cells loaded with autologous tumor lysate
      or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis
      IFN-alpha in patients with metastatic melanoma: a randomised "proof-of-principle"
      phase II study.
AB  - BACKGROUND: Vaccination with dendritic cells (DC) loaded with tumor antigens
      elicits tumor-specific immune responses capable of killing cancer cells without
      inducing meaningful side-effects. Patients with advanced melanoma enrolled onto
      our phase II clinical studies have been treated with autologous DC loaded with
      autologous tumor lysate/homogenate matured with a cytokine cocktail, showing a
      clinical benefit (PR + SD) in 55.5% of evaluable cases to date. The beneficial
      effects of the vaccine were mainly restricted to patients who developed vaccine
      specific immune response after treatment. However, immunological responses were
      only induced in about two-thirds of patients, and treatments aimed at improving
      immunological responsiveness to the vaccine are needed. METHODS/DESIGN: This is a
      phase II, "proof-of-principle", randomized, open-label trial of vaccination with
      autologous DC loaded with tumor lysate or homogenate in metastatic melanoma
      patients combined with immunomodulating RT and/or preleukapheresis IFN-alpha. All
      patients will receive four bi-weekly doses of the vaccine during the induction
      phase and monthly doses thereafter for up to a maximum of 14 vaccinations or
      until confirmed progression. Patients will be randomized to receive:(1.) three
      daily doses of 8 Gy up to 12 Gy radiotherapy delivered to one non-index
      metastatic field between vaccine doses 1 and 2 and, optionally, between doses 7
      and 8, using IMRT-IMAT techniques;(2.) daily 3 MU subcutaneous IFN-alpha for 7
      days before leukapheresis;(3.) both 1 and 2;(4.) neither 1 nor 2.At least six
      patients eligible for treatment will be enrolled per arm. Daily 3 MU IL-2 will be
      administered subcutaneously for 5 days starting from the second day after each
      vaccine dose. Serial DTH testing and blood sampling to evaluate treatment-induced
      immune response will be performed. Objective response will be evaluated according
      to immune-related response criteria (irRC). DISCUSSION: Based upon the emerging
      role of radiotherapy as an immunologic modifier, we designed a randomized phase
      II trial adding radiotherapy and/or preleukapheresis IFN-alpha to our DC vaccine
      in metastatic melanoma patients. Our aim was to find the best combination of
      complementary interventions to enhance anti-tumor response induced by DC
      vaccination, which could ultimately lead to better survival and milder toxicity.

PMID- 25053131
TI  - Y grafts with the left internal mammary artery and radial artery. Mid-term
      functional and angiographic results. Cohort study.
AB  - BACKGROUND: This retrospective cohort study investigated the functional and
      haemodynamic mid-term results over 3-years follow up of the left internal mammary
      artery (LIMA) conduit in composite Y-graft configuration with radial artery (RA)
      in a population of patients who underwent off-pump coronary artery bypass
      grafting (CABG). METHODS: 148 patients who underwent off-pump CABG with composite
      Y-graft, were evaluated over 3-year follow up. Two-day dipyridamole induced
      maximal hyperaemia/rest 99mTc-sestamibi was scheduled preoperatively and 36
      months after surgery for functional evaluation. Morphological evaluation was
      performed by 64 slice multidetector computed tomography (CT) 36 months after
      surgery. RESULTS: Clinical adverse events were rare within 3 years follow up.
      Minimal to severe scintigraphic evidence of stress induced ischaemia occurred in
      24 patients. Left ventricular (LV) hypertrophy (HR 3.1; 95% CI, 1.5-9.3; p =
      0.01) and poor coronary run off (HR 4.1; 95% CI, 2.1-10.8; p = 0.005) were
      significant multivariate predictors of reversible stress induced ischaemia. 64
      slice multidetector CT showed that the main stem of Y composite grafts was patent
      in all patients, while distal LIMA or RA was stenosed or occluded in 9 patients.
      CONCLUSION: Composite Y-graft was adequate to meet the flow requirements of
      target coronary artery either at rest or during maximal hyperaemia. The use of Y
      graft should be carefully evaluated in patients with LV hypertrophy and/or poor
      coronary run-off.

PMID- 25053132
TI  - Can the common-sense model predict adherence in chronically ill patients? A meta
      analysis.
AB  - The aim of this meta-analysis was to explore whether mental representations,
      derived from the common-sense model of illness representations (CSM), were able
      to predict adherence in chronically ill patients. Electronic databases were
      searched for studies that used the CSM and measured adherence behaviour in
      chronically ill patients. Correlations from the included articles were meta
      analysed using a random-size effect model. A moderation analysis was conducted
      for the type of adherence behaviour. The effect sizes for the different mental
      representations and adherence constructs ranged from -0.02 to 0.12. Further
      analyses showed that the relationship between the mental representations and
      adherence did not differ by the type of adherence behaviour. The low-effect sizes
      indicate that the relationships between the different mental representations of
      the CSM and adherence are very weak. Therefore, the CSM may not be the most
      appropriate model to use in predictive studies of adherence. 

PMID- 25053133
TI  - Social comparisons and chronic illness: research synthesis and clinical
      implications.
AB  - The chronically ill patient must adjust to new life circumstances and manage
      ongoing threats to personal health. Patients often make comparisons with each
      other, which can have effects on their psychological and physical well-being. One
      question is whether health psychologists can develop interventions to
      strategically facilitate the use of such comparisons to optimise adjustment. This
      paper critically reviews evidence on patients' comparisons in studies using
      selection, narration and reaction methods. Discussion focuses on gaps in the
      empirical literature and describes some new basic concepts in social comparison,
      which may advance knowledge about the process in medical patients.
      Recommendations also are provided about the kinds of studies needed to inform the
      future design of effective social comparison interventions. 

PMID- 25053134
TI  - Social history of health psychology: context and textbooks.
AB  - Health psychology as a field of research and practice formally developed 30 years
      ago but it was prefigured by sustained debate within social and applied
      psychology about the nature of psychology and its role in society. This article
      considers this pre-history of health psychology and how the field has
      subsequently developed. It considers how its character is shaped by dominant
      ideas within psychology and is also enmeshed in broader social relations. To
      illustrate the changing character of health psychology it considers how the field
      is represented in a selection of popular textbooks. It concludes by considering
      the growth of some critical approaches within health psychology. 

PMID- 25053135
TI  - Revolutionary health psychology versus scientific health psychology - commentary
      on Murray (2012).

PMID- 25053136
TI  - The changing shape of health psychology: a matter of progress or a sign of
      Thatcher's children coming of age? Commentary on Murray (2012).

PMID- 25053137
TI  - The time has come to talk of many things: some comments on Ogden and Friedman.

PMID- 25053139
TI  - Genetic association between a 'standing' variant of NOD2 and bipolar disorder.
AB  - Bipolar disorders (BD) are chronic, multisystem and multifactorial disorders with
      significant lifetime morbidity, mortality and socio-economic burden.
      Understanding the underlying genetic and disease triggering environmental factors
      should improve diagnosis, prognosis, prevention and therapeutic management of the
      disease. Since intestinal innate dysimmunity seems to play a significant role in
      the etiopathogeny of BD, we explored in a sample of French Caucasian BD patients,
      the genetic polymorphisms of NOD2 (nucleotide-binding oligomerization domain
      containing 2) gene, a key player in such immunity. We found a Caucasian-specific
      'standing' variation to be associated with BD. The significance of this finding
      is discussed in the context of Crohn's disease as well as the complex function of
      NOD2 in innate immunity. 

PMID- 25053141
TI  - Interpolation of extensive routine water pollution monitoring datasets:
      methodology and discussion of implications for aquifer management.
AB  - A large fraction of the fresh water available for human use is stored in
      groundwater aquifers. Since human activities such as mining, agriculture,
      industry and urbanisation often result in incursion of various pollutants to
      groundwater, routine monitoring of water quality is an indispensable component of
      judicious aquifer management. Unfortunately, groundwater pollution monitoring is
      expensive and usually cannot cover an aquifer with the spatial resolution
      necessary for making adequate management decisions. Interpolation of monitoring
      data is thus an important tool for supplementing monitoring observations.
      However, interpolating routine groundwater pollution data poses a special problem
      due to the nature of the observations. The data from a producing aquifer usually
      includes many zero pollution concentration values from the clean parts of the
      aquifer but may span a wide range of values (up to a few orders of magnitude) in
      the polluted areas. This manuscript presents a methodology that can cope with
      such datasets and use them to produce maps that present the pollution plumes but
      also delineates the clean areas that are fit for production. A method for
      assessing the quality of mapping in a way which is suitable to the data's dynamic
      range of values is also presented. A local variant of inverse distance weighting
      is employed to interpolate the data. Inclusion zones around the interpolation
      points ensure that only relevant observations contribute to each interpolated
      concentration. Using inclusion zones improves the accuracy of the mapping but
      results in interpolation grid points which are not assigned a value. The inherent
      trade-off between the interpolation accuracy and coverage is demonstrated using
      both circular and elliptical inclusion zones. A leave-one-out cross testing is
      used to assess and compare the performance of the interpolations. The methodology
      is demonstrated using groundwater pollution monitoring data from the coastal
      aquifer along the Israeli shoreline. The implications for aquifer management are
      discussed.

PMID- 25053140
TI  - Cholesterol crystal-induced endothelial cell activation is complement-dependent
      and mediated by TNF.
AB  - Cholesterol crystals are known to be a hallmark of atherosclerosis with recent
      studies demonstrating deposition of these crystals in early fatty streak
      formation as well as penetrating the intima following plaque rupture.
      Inflammation has also become a central focus in atheroma development and
      endothelial cell activation is recognized as necessary for the recruitment of
      inflammatory cells to the plaque. However, the extent to which cholesterol
      crystals can induce inflammation and activate endothelial cells is not known. To
      investigate this, we developed a novel model activating human umbilical vein
      endothelial cells using lepirudin anticoagulated human whole blood. We found that
      cholesterol crystals caused a marked and dose-dependent increase in the adhesion
      molecules E-selectin and ICAM-1 on the surface of the endothelial cells after
      incubation with whole blood. There was no activation of the cells when the
      crystals were incubated in medium alone, or in human serum, despite substantial
      crystal-induced complement activation in serum. Complement inhibitors at the C3
      and C5 levels reduced the whole blood induced endothelial cell activation by up
      to 89% (p<0.05) and abolished TNF release (p<0.01). Finally, the TNF inhibitor
      infliximab reduced endothelial activation to background levels (p<0.05). In
      conclusion, these data demonstrate that endothelial activation by cholesterol
      crystals is mediated by complement-dependent TNF release, and suggests that
      complement-inhibition might have a role in alleviating atherosclerosis-induced
      inflammation. 

PMID- 25053142
TI  - Suffix tree searcher: exploration of common substrings in large DNA sequence
      sets.
AB  - BACKGROUND: Large DNA sequence data sets require special bioinformatics tools to
      search and compare them. Such tools should be easy to use so that the data can be
      easily accessed by a wide array of researchers. In the past, the use of suffix
      trees for searching DNA sequences has been limited by a practical need to keep
      the trees in RAM. Newer algorithms solve this problem by using disk-based
      approaches. However, none of the fastest suffix tree algorithms have been
      implemented with a graphical user interface, preventing their incorporation into
      a feasible laboratory workflow. RESULTS: Suffix Tree Searcher (STS) is designed
      as an easy-to-use tool to index, search, and analyze very large DNA sequence
      datasets. The program accommodates very large numbers of very large sequences,
      with aggregate size reaching tens of billions of nucleotides. The program makes
      use of pre-sorted persistent "building blocks" to reduce the time required to
      construct new trees. STS is comprised of a graphical user interface written in
      Java, and four C modules. All components are automatically downloaded when a web
      link is clicked. The underlying suffix tree data structure permits extremely fast
      searching for specific nucleotide strings, with wild cards or mismatches allowed.
      Complete tree traversals for detecting common substrings are also very fast. The
      graphical user interface allows the user to transition seamlessly between
      building, traversing, and searching the dataset. CONCLUSIONS: Thus, STS provides
      a new resource for the detection of substrings common to multiple DNA sequences
      or within a single sequence, for truly huge data sets. The re-searching of
      sequence hits, allowing wild card positions or mismatched nucleotides, together
      with the ability to rapidly retrieve large numbers of sequence hits from the DNA
      sequence files, provides the user with an efficient method of evaluating the
      similarity between nucleotide sequences by multiple alignment or use of Logos.
      The ability to re-use existing suffix tree pieces considerably shortens index
      generation time. The graphical user interface enables quick mastery of the
      analysis functions, easy access to the generated data, and seamless workflow
      integration.

PMID- 25053143
TI  - Comparative proteomic analysis of different developmental stages of the edible
      mushroom Termitomyces heimii.
AB  - BACKGROUND: Termitomyces heimii is a basidiomycete fungus that has a symbiotic
      relationship with termites, and it is an edible mushroom with a unique flavour
      and texture. T. heimii is also one of the most difficult mushrooms to cultivate
      throughout the world. Little is known about the growth and development of these
      mushrooms, and the available information is insufficient or poor. The purpose of
      this study was to provide a base of knowledge regarding the biological processes
      involved in the development of T. heimii. The proteomic method of 2 dimensional
      difference gel electrophoresis 2D-DIGE was used to determine and examine the
      protein profiles of each developmental stage (mycelium, primordium and fruiting
      body). Total proteins were extracted by TCA-acetone precipitation. RESULTS: A
      total of 271 protein spots were detected by electrophoresis covering pH 3-10 and
      10-250 kDa. Selected protein spots were subjected to mass spectrometric analyses
      with matrix-assisted laser desorption/ionisation (MALDI TOF/TOF). Nineteen
      protein spots were identified based on peptide mass fingerprinting by matching
      peptide fragments to the NCBI non-redundant database using MASCOT software. The
      19 protein spots were categorised into four major groups through KEGG pathway
      analysis, as follows: carbohydrate metabolism, energy metabolism, amino acid
      metabolism and response to environmental stress. CONCLUSIONS: The results from
      our study show that there is a clear correlation between the changes in protein
      expression that occur during different developmental stages. Enzymes related to
      cell wall synthesis were most highly expressed during fruiting body formation
      compared to the mycelium and primordial stages. Moreover, enzymes involved in
      cell wall component degradation were up-regulated in the earlier stages of
      mushroom development.

PMID- 25053144
TI  - Food, food choice and nutrition promotion in a remote Australian Aboriginal
      community.
AB  - Contemporary diets of Aboriginal people living in remote Australia are
      characterised by processed foods high in fat and sugar. Within the 'new' food
      system, evidence suggests many Aboriginal people understand food in their own
      terms but lack access to consumer information about store-purchased foods, and
      parents feel inadequate as role models. In a remote Australian Aboriginal
      community, purposive sampling identified adults who participated in
      semistructured interviews guided by food-based themes relating to the
      contemporary food system, parental guidance of children's food choice and
      channels through which people learn. Interpretive content analysis was used to
      identify salient themes. In discussions, people identified more closely with
      dietary qualities or patterns than nutrients, and valued a balanced, fresh diet
      that made them feel 'light'. People possessed basic knowledge of 'good' store
      foods, and wanted to increase familiarity and experience with foods in packets
      and cans through practical and social skills, especially cooking. Education about
      contemporary foods was obtained from key family role models and outside the home
      through community-based organisations, including school, rather than pamphlets
      and flip charts. Freedom of choice was a deeply held value; carers who challenged
      children's autonomy used strategic distraction, or sought healthier alternatives
      that did not wholly deny the child. Culturally safe approaches to information
      sharing and capacity building that contribute to the health and wellbeing of
      communities requires collaboration and shared responsibility between policy
      makers, primary healthcare agencies, wider community-based organisations and
      families. 

PMID- 25053145
TI  - Jasmonic acid signalling mediates resistance of the wild tobacco Nicotiana
      attenuata to its native Fusarium, but not Alternaria, fungal pathogens.
AB  - We recently characterized a highly dynamic fungal disease outbreak in native
      populations of Nicotiana attenuata in the southwestern United States. Here, we
      explore how phytohormone signalling contributes to the observed disease dynamics.
      Single inoculation with three native Fusarium and Alternaria fungal pathogens,
      isolated from diseased plants growing in native populations, resulted in disease
      symptoms characteristic for each pathogen species. While Alternaria sp.-infected
      plants displayed fewer symptoms and recovered, Fusarium spp.-infected plants
      became chlorotic and frequently spontaneously wilted. Jasmonic acid (JA) and
      salicylic acid (SA) levels were differentially induced after Fusarium or
      Alternaria infection. Transgenic N. attenuata lines silenced in JA production or
      JA conjugation to isoleucine (JA-Ile), but not in JA perception, were highly
      susceptible to infection by F. brachygibbosum Utah 4, indicating that products
      derived from the JA-Ile biosynthetic pathway, but not their perception, is
      associated with increased Fusarium resistance. Infection assays using ov-nahG
      plants which were silenced in pathogen-induced SA accumulations revealed that SA
      may increase N. attenuata's resistance to Fusarium infection but not to
      Alternaria. Taken together, we propose that the dynamics of fungal disease
      symptoms among plants in native populations may be explained by a complex
      interplay of phytohormone responses to attack by multiple pathogens. 

PMID- 25053146
TI  - [Comments to the article "Spanish anesthesiologists approach on intraoperative
      awareness with explicit recall. Results of a national survey performed in 2011"].

PMID- 25053147
TI  - The Perspectives of Six Latino Heritage Groups About Their Health Care.
AB  - The Latino population in the US is projected to grow substantially in the years
      ahead. Although often referred to as a single group, Latinos are not homogeneous.
      This article, based mainly on a national telephone survey of 1,478 Latino adults,
      examines the perspectives of six Latino heritage groups on the health care issues
      they face. The six groups differ in their reported health care experiences in:
      the types facilities they use in getting medical care, their ratings of the
      quality of care they receive, their experiences with discrimination in getting
      quality care, the level of confidence they have in being able to pay for a major
      illness. One thing the heritage groups agree on is that diabetes is the biggest
      health problem facing their families. Community health leaders, particularly at
      the state level, need to focus on the specific Latino groups in their state or
      area and their unique situations. 

PMID- 25053148
TI  - Chiral lithium diamides derived from linked N-isopropyl valinol or alaninol.
AB  - Four different chiral diamino diethers synthesized from N-isopropyl valinol or N
      isopropyl alaninol were lithiated with n-butyllithium in tetrahydrofuran or
      diethyl ether. Crystal structures of the dilithiated diamino diethers were
      determined by X-ray diffraction. Three dilithiated diamino diethers including
      (2S,2'S)-1,1'-(butane-1,4-diylbis(oxy))bis(N-isopropylpropan-2-amine) 7, (2S,2'S)
      1,1'-(pentane-1,5-diylbis(oxy))bis(N-isopropylpropan-2-amine) 8, and (2S,2'S)
      1,1'-(heptane-1,7-diylbis(oxy))bis(N-isopropyl-3-methylbutan-2-amine) 9 are
      dimers, whereas dilithiated (2S,2'S)-1,1'-(pentane-1,5-diylbis(oxy))bis(N
      isopropyl-3-methylbutan-2-amine) 10 is a monomer. The lithium atoms in all
      crystal structures adopt a nonequivalent coordination protocol and exist in two
      different environments in which one of the lithium atoms is tetra-coordinated
      while the other one is tri-coordinated. The solution structures of the
      dilithiated diamino diethers are also characterized by a variety of NMR
      experiments including diffusion-ordered NMR spectroscopy (DOSY) with diffusion
      coefficient-formula (D-FW) weight correlation analyses and other one- and two
      dimensional NMR techniques. 

PMID- 25053151
TI  - Safe removal of long-term venous catheters in the neck.
AB  - AIMS: Tunnelled venous catheters are a well-established method of long-term
      venous access for total parental nutrition, chemotherapy and antimicrobial
      treatment. Removal of these catheters is a simple procedure; however, there are
      some significant risks. METHODS: We report a case in which a serious complication
      occurred. A simple technique for the safe removal of long-term venous catheters
      is described. CONCLUSION: A direct surgical removal is now generally favoured for
      safe line removal. However, this still carries the same complications and care
      must be taken in the technique.

PMID- 25053150
TI  - Caregiver distress in first-episode psychosis: the role of subjective appraisal,
      over-involvement and symptomatology.
AB  - BACKGROUND: Caregivers of persons with first-episode psychosis (FEP) often report
      high levels of distress. Preventing long-term or chronic distress within the
      whole family is an important focus of early intervention for psychosis. However,
      a more comprehensive understanding of the psychological factors involved is
      needed. AIMS: To examine the impact of subjective appraisals and expressed
      emotion on caregiver distress in FEP. METHOD: Within a cross-sectional design,
      154 caregivers of 99 persons with FEP in a clinical epidemiological sample
      completed a series of questionnaires to examine potential predictors of caregiver
      distress. RESULTS: Thirty-seven percent of caregivers were suffering from
      clinically significant distress. A linear mixed model analysis found that, after
      controlling for caregiver socio-demographic factors, service-user symptoms and
      global functioning, emotional over-involvement and subjective appraisal of
      caregiving were significant predictors of caregiver distress. CONCLUSION:
      Caregiver distress is significant in the early phase of illness, and this seems
      to be more related to their subjective appraisal and over-involvement, than to
      variations in symptoms and global functioning of the person diagnosed with FEP.
      This lends further support to the stress-appraisal coping model and the cognitive
      model of caregiving in FEP, and highlights supportive interventions aimed at
      handling unhelpful cognitions and behaviors.

PMID- 25053149
TI  - Relationships of perceived public stigma of mental illness and psychosis-like
      experiences in a non-clinical population sample.
AB  - PURPOSE: Studies on the association between psychopathology, perceived public
      stigma, and labeling in mental illness have focused primarily on severe but rare
      mental disorders, especially schizophrenia, or other clinically defined psychotic
      disorders. Although evidence is mounting that psychosis-like experiences show
      high prevalence in the general population and lead to an increased risk of
      psychotic disorders, little is known about how psychosis-like experiences
      independently affect perceived public stigma in the non-clinical population. The
      aim of the present study was to examine the relationship between psychosis-like
      experiences and perceived public stigma in a non-clinical sample. METHODS: For
      this cross-sectional study, we recruited 524 individuals (239 male, 285 female)
      who had no lifetime history of psychiatric disorder. Participants completed
      questionnaires that asked for sociodemographic and clinical information, a
      measure of perceived public stigma (Perceived Psychiatric Stigma Scale [PPSS]),
      and two measures of psychosis-like experiences (Peters et al. Delusions Inventory
      [PDI]; Cardiff Anomalous Perceptions Scale [CAPS]). RESULTS: Of the
      sociodemographic characteristics analyzed in this study-gender, age, education
      level, marital status, and religion-only age simultaneously influenced PPSS, PDI,
      and CAPS scores. As hypothesized, perceived public stigma was positively
      correlated with measures of psychosis-like experiences, even after controlling
      for age. Furthermore, the perceived stigma was more strongly associated with
      delusion proneness than with anomalous perceptual experiences. CONCLUSION: The
      association between psychopathology and perceived public stigma appears to extend
      beyond clinically defined psychosis to more common psychosis-like experiences in
      a sample drawn from the general Han Chinese population.

PMID- 25053152
TI  - An evaluation of commissioning arrangements for intrauterine and subdermal
      contraception services from general practitioners in London, UK.
AB  - OBJECTIVES: General practitioners (GPs) in the UK may be commissioned to provide
      long-acting reversible contraception (LARC), which may have a role in reducing
      rates of abortion and unintended pregnancies. Primary care trusts (PCTs) in
      England had commissioning arrangements with GPs to provide LARC but little is
      known about such contractual arrangements. We studied the commissioning
      arrangements in some London PCTs to evaluate the cost and clinical governance of
      these contracts. METHODS: We requested commissioning contract specifications and
      activities for intrauterine contraception (IUC) and subdermal implants (SDI) from
      responsible officers in each PCT in London relating to activities in three
      financial years, namely 2009/2010 to 2011/2012. We evaluated each contract using
      a structure, process and outcome approach. RESULTS: Half (15/31) the PCTs
      responded and submitted 20 contracts used to commission their GPs to provide IUC,
      SDI or a combination of these with testing for sexually transmitted infections.
      The information regarding service activity was inadequate and inconsistent so had
      to be abandoned. Information from 20 contracts suggested there was a variation in
      clinical governance and quality assurance mechanisms; there was also a range in
      the reimbursement for IUC insertion (L77.50 to L105.00), SDI insertion (L25.00 to
      L81.31) and SDI removal (L30.00 to L100.00) at 2011 prices. CONCLUSION: It was
      not clear from non-responders if these PCTs had a service in place. Of those that
      did commission IUC and SDI services, some specifications were lacking in detail
      regarding aspects of clinical governance. New commissioners should make explicit
      references to quality and safety criteria as poor-quality specifications can give
      rise to serious untoward incidents and litigation.

PMID- 25053154
TI  - Reversible homonymous hemianopia secondary to occipital lobe seizures.

PMID- 25053153
TI  - Social anxiety and self-concept in children with epilepsy: a pilot intervention
      study.
AB  - PURPOSE: The purpose of this study was to assess the impact of a cognitive
      behavioral therapy (CBT) anxiety intervention on social phobia, social skill
      development, and self-concept. METHOD: Fifteen children with epilepsy and a
      primary anxiety disorder participated in a CBT intervention for 12 weeks plus a 3
      month follow-up visit. Children were assessed at baseline, week 7, week 12, and 3
      months post treatment to measure changes in social phobia using the Screen for
      Child Anxiety Related Emotional Disorders (SCARED). Self-concept was also
      assessed by using the Piers-Harris Children's Self-Concept Scale II (Piers-Harris
      2). RESULTS: There was a significant reduction in symptoms of social phobia and
      improved self-concept at the end of the 12-week intervention and at the 3 month
      follow-up. Repeated measures ANOVA's of child ratings revealed significant change
      over time on the SCARED-Social Phobia/Social Anxiety subscale score (p=0.024). In
      terms of self-concept, significant change over time was detected on the Piers
      Harris 2-Total score (p=0.015) and several subscale scores of Piers-Harris 2,
      including: Physical Appearance and Attributes (p=0.016), Freedom from Anxiety
      (p=0.005), and Popularity (p=0.003). CONCLUSION: This pilot investigation
      utilized an evidenced based CBT intervention to reduce symptoms of social phobia,
      which in turn provided a vehicle to address specific social skills improving self
      concept in children with epilepsy.

PMID- 25053155
TI  - Congenital ankyloblepharon in a leopard gecko (Eublepharis macularius).
AB  - A 6-month-old leopard gecko with unilateral partially fused eyelids since birth
      was presented for examination. A diagnosis of congenital ankyloblepharon was made
      and surgical correction was performed successfully. 

PMID- 25053156
TI  - Recommendations for anesthesia and perioperative management in patients with
      Ehlers-Danlos syndrome(s).
AB  - Ehlers-Danlos syndrome (EDS, ORPHA98249) comprises a group of clinically and
      genetically heterogeneous heritable connective tissue disorders, chiefly
      characterized by joint hypermobility and instability, skin texture anomalies, and
      vascular and soft tissue fragility. As many tissues can be involved, the
      underlying molecular defect can manifest itself in many organs and with varying
      degrees of severity, with widespread implications for anesthesia and
      perioperative management. This review focuses on issues relevant for anesthesia
      for elective and emergency surgery in EDS. We searched the literature for papers
      related to all EDS variants; at the moment most of the published data deals with
      the vascular subtype and, to a lesser extent, classic and hypermobility EDS.
      Knowledge is fragmented and consists mostly of case reports, small case series
      and expert opinion. Because EDS patients commonly require surgery, we have
      summarized some recommendations for general, obstetrical and regional anesthesia,
      as well as for hemostatic therapy. 

PMID- 25053157
TI  - Factors associated with prolonged non-nutritive sucking habits in two cohorts of
      Brazilian children.
AB  - BACKGROUND: Non-nutritive sucking habits (NNSH) are very common during childhood.
      However, if these habits were maintained for 36 months of age or more, they are
      considered to be prolonged (PNNSH) and can cause occlusal, physiological and
      esthetic changes. There is controversy about their prevalence and whether
      perinatal, social, demographic and health characteristics influence their onset
      and duration. So, the objectives of this study are to estimate the prevalence of
      PNNSH and to evaluate perinatal, early life and school age factors associated
      with their occurrence in children. METHODS: A sample of 1,463 children aged 7-11
      years born in Ribeirao Preto (RP-1994) and Sao Luis (SL-1997/98), Brazil, was
      reevaluated at school age in 2004/05. Birth weight, gestational age and perinatal
      variables were obtained at birth. Type of feeding, occurrence and duration of
      finger and pacifier sucking were recorded retrospectively at school age. PNNSH
      were defined when persisted for 36 months of age or more. Crude and adjusted
      prevalence ratios (PR) were estimated by Poisson regression (alpha = 5%).
      RESULTS: Prevalence of PNNSH was higher in RP (47.6%) than in SL (20.2%) - (p <
      0.001). Perinatal variables were not associated to PNNSH, whilst female sex (PR =
      1.27 in RP; PR = 1.47 in SL) and bottle feeding for 24 months or more (PR = 2.24
      in RP; PR = 2.49 in SL) were risk factors in both locations. Breast feeding for
      12 months or more (PR = 0.53 in RP; PR = 0.31 in SL) was associated with lower
      prevalence of PNNSH in both places. In SL, children whose mothers lived in
      consensual union (PR = 1.62) and worked outside the home (PR = 1.51) showed
      higher prevalence of PNNSH compared to their counterparts. CONCLUSIONS:
      Prevalence of PNNSH was high especially in RP and was not associated with
      perinatal variables. In both cities there was an association between female sex,
      shorter breast-feeding duration, longer bottle feeding duration and higher
      prevalence of PNNSH.

PMID- 25053158
TI  - Long-term rearing of Arctic charr Salvelinus alpinus under different salinity
      regimes at constant temperature.
AB  - Arctic charr Salvelinus alpinus of the Holar strain (mean +/- s.e. body mass =
      152.1 +/- 3.1 g) were reared at four different salinity regimes at a constant
      temperature of 7.4 degrees  C. Two groups were given a three-month acclimation in
      salinity 18 before the salinity was increased to either 25 or 29 (groups called
      A25 and A29), and two groups were reared in salinities 25 or 29 over the full
      experimental period of 409 days (groups called F25 and F29). In the first 3
      months, the A25 and A29 groups had the highest growth rates. By October 2011,
      there were no significant differences (two-way nested ANOVA, P > 0.05) in the
      mean body masses among A25, F25 and F29 (c. 1450 g), whereas A29 had a lower mean
      mass (1282 g). The growth in the last period from October 2011 to January 2012
      was reduced by sexual maturation in the highest salinity regimes (A29 and F29),
      whereas fish in groups A25 and F25 showed high growth throughout the study. Males
      in all salinity groups had higher growth rates than females for the most part of
      the study, but the divergence between the sexes was most pronounced in the
      highest salinity regimes. All salinity groups showed distinct changes in Na(+) ,
      K(+) -ATPase activity, with high activity in spring and summer, and lower
      activity in the autumn. Plasma sodium (Na(+) ) levels were stable indicating that
      none of the experimental groups had problems in maintaining hydromineral balance
      during the study. While plasma leptin levels were not affected by salinity
      regimes, it was noted that these levels were 13-30% higher in fish with empty
      guts compared with those having food in their gut at the time of sampling. This
      suggests a link between leptin levels and food intake, indicating that this
      hormone may play a role in food intake and energy allocation in fishes.

PMID- 25053159
TI  - Conservation covenants on private land: issues with measuring and achieving
      biodiversity outcomes in Australia.
AB  - Conservation covenants and easements have become essential tools to secure
      biodiversity outcomes on private land, and to assist in meeting international
      protection targets. In Australia, the number and spatial area of conservation
      covenants has grown significantly in the past decade. Yet there has been little
      research or detailed policy analysis of conservation covenanting in Australia. We
      sought to determine how conservation covenanting agencies were measuring the
      biodiversity conservation outcomes achieved on covenanted properties, and factors
      inhibiting or contributing to measuring these outcomes. In addition, we also
      investigated the drivers and constraints associated with actually delivering the
      biodiversity outcomes, drawing on detailed input from covenanting programs.
      Although all conservation covenanting programs had the broad aim of maintaining
      or improving biodiversity in their covenants in the long term, the specific
      stated objectives of conservation covenanting programs varied. Programs undertook
      monitoring and evaluation in different ways and at different spatial and temporal
      scales. Thus, it was difficult to determine the extent Australian conservation
      covenanting agencies were measuring the biodiversity conservation outcomes
      achieved on covenanted properties on a national scale. Lack of time available to
      covenantors to undertake management was one of the biggest impediments to
      achieving biodiversity conservation outcomes. A lack of financial resources and
      human capital to monitor, knowing what to monitor, inconsistent monitoring
      methodologies, a lack of benchmark data, and length of time to achieve outcomes
      were all considered potential barriers to monitoring the biodiversity
      conservation outcomes of conservation covenants. 

PMID- 25053160
TI  - The potential for double-loop learning to enable landscape conservation efforts.
AB  - As conservation increases its emphasis on implementing change at landscape-level
      scales, multi-agency, cross-boundary, and multi-stakeholder networks become more
      important. These elements complicate traditional notions of learning. To
      investigate this further, we examined structures of learning in the Landscape
      Conservation Cooperatives (LCCs), which include the entire US and its
      territories, as well as parts of Canada, Mexico, and Caribbean and Pacific island
      states. We used semi-structured interviews, transcribed and analyzed using NVivo,
      as well as a charrette-style workshop to understand the difference between the
      original stated goals of individual LCCs and the values and purposes expressed as
      the collaboration matured. We suggest double-loop learning as a theoretical
      framework appropriate to landscape-scale conservation, recognizing that concerns
      about accountability are among the valid points of view that must be considered
      in multi-stakeholder collaborations. Methods from the social sciences and public
      health sectors provide insights on how such learning might be actualized.

PMID- 25053161
TI  - Relative validity and reproducibility of a food frequency questionnaire used in
      pregnant women from a rural area of China.
AB  - OBJECTIVE: Food frequency questionnaires are relatively inexpensive, easy and
      quick to administer, but the construction of a food frequency questionnaire that
      can capture Chinese food habits is challenging given the diverse lifestyle and
      eating habits in different parts of the country. The aim of this study was to
      assess the validity and reproducibility of a self-administered food frequency
      questionnaire against a 3-day dietary recall in a rural region of western China.
      DESIGN: Prospective cohort study. SETTING: Chinese maternal and child healthcare
      hospital. POPULATION: A total of 168 healthy pregnant women. METHODS: Pregnant
      women completed a food frequency questionnaire at 16-24 weeks gestation, and
      again at 29-31 weeks; during weeks 26-27 they completed a 3-day dietary recall.
      RESULTS: In general, mean intake was higher when assessed with food frequency
      questionnaires compared with dietary recall. Spearman and intra-class correlation
      coefficients between the two food frequency questionnaires ranged from 0.31 to
      0.69 and from 0.27 to 0.79, respectively. For the second food frequency
      questionnaire and the dietary recall, the crude and de-attenuated Spearman
      correlations ranged from 0.12 to 0.55 and 0.14 to 0.58, respectively. The
      correlation both between the two food frequency questionnaires and between the
      second food frequency questionnaire and the dietary recall decreased after
      adjustment for energy. Ranking women, 31-57% and 1-8% were classified into the
      same and the opposite quartile, respectively, by both food frequency
      questionnaires; 30-45% and 1-11% were classified into the same and the opposite
      quartile respectively for the second food frequency questionnaire and dietary
      recall. CONCLUSION: The food frequency questionnaire showed good reproducibility
      and correlations with dietary recall; it is useful for ranking study participants
      according to dietary intake, which is of great importance to future etiological
      studies in this cohort.

PMID- 25053162
TI  - Triptycene based organometallic complexes: a new class of acceptor synthons for
      supramolecular ensembles.
AB  - Preparation and characterization of two new triptycene based polytopic Pt(II)
      organometallic complexes are being reported. These complexes have three trans
      bromobis(trialkylphosphine)platinum(II) units directly attached to the central
      triptycene unit. These organoplatinum complexes were converted to the
      corresponding nitrate salts for subsequent use in self-assembly reactions.
      Characterization of these organometallic triptycene complexes by multinuclear
      NMR, FTIR, mass spectrometry and elemental analyses is described. The molecular
      structure of one of the organoplatinum triptycene tripods was determined by
      single-crystal X-ray crystallography. The potential utility of these
      organometallic tritopic acceptors as building blocks in the construction of
      metallasupramolecular cages containing the triptycene motif is explored.
      Additionally, for the first time, 3,3'-bipyridine has been used as a flexible
      donor tecton for self-assembly of discrete and finite metallacages using
      triptycene based tritopic organometallic acceptor units. Triptycene motif
      containing supramolecules were characterized by multinuclear NMR (including (1)H
      DOSY), mass spectrometry and elemental analyses. Geometry of each supramolecular
      framework was optimized by employing the PM6 semiempirical molecular orbital
      method to predict its shape and size.

PMID- 25053163
TI  - The pathogenomics of McArdle disease--genes, enzymes, models, and therapeutic
      implications.
AB  - Numerous biomedical advances have been made since Carl and Gerty Cori discovered
      the enzyme phosphorylase in the 1940s and the Scottish physician Brian McArdle
      reported in 1951 a previously 'undescribed disorder characterized by a gross
      failure of the breakdown in muscle of glycogen'. Today we know that this
      disorder, commonly known as 'McArdle disease', is caused by inherited deficiency
      of the muscle isoform of glycogen phosphorylase (GP). Here we review the main
      aspects of the 'pathogenomics' of this disease including, among others: the
      spectrum of mutations in the gene (PYGM) encoding muscle GP; the interplay
      between the different tissue GP isoforms in cellular cultures and in patients;
      what can we learn from naturally occurring and recently laboratory-generated
      animal models of the disease; and potential therapies. 

PMID- 25053164
TI  - Autotaxin downregulates LPS-induced microglia activation and pro-inflammatory
      cytokines production.
AB  - Inflammation is essential in defense against infection or injury. It is tightly
      regulated, as over-response can be detrimental, especially in immune-privileged
      organs such as the central nervous system (CNS). Microglia constitutes the major
      source of inflammatory factors, but are also involved in the regulation of the
      inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts
      lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA) and is upregulated
      in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce
      multiple cellular processes including morphological changes, proliferation,
      death, and survival. We investigated ATX effects on microglia inflammatory
      response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine
      BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A +) microglia
      were treated with LPS. Tumor necrosis factor alpha (TNFalpha), interleukin (IL)
      6, and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA,
      respectively. Secreted LPA was quantified by a radioenzymatic assay and
      microglial activation markers (CD11b, CD14, B7.1, and B7.2) were determined by
      flow cytometry. ATX expression and LPA production were significantly enhanced in
      LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNFalpha and
      IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and
      B7.1, and B7.2 expressions were reduced in A+ cells. Our results strongly suggest
      deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced
      microglia activation.

PMID- 25053165
TI  - IL-1beta microenvironment promotes proliferation, migration, and invasion of
      human glioma cells.
AB  - Among the primary brain tumors, glioblastoma is the most common and severe.
      Glioblastoma have poor prognosis because of their highly diffusive growth pattern
      and invasion into surrounding brain tissue. Human glioblastoma cells overexpress
      interleukin-1beta (IL-1beta) and also the levels of IL-1beta in U87MG glioma
      cells are significantly higher than in U373, T98G, A172 glioma cell lines.
      Malignant tumors are characterized by unlimited proliferation, migration and
      invasion. This study examines the effect of IL-1beta microenvironment on
      proliferation, migration and invasion in human glioma cell line U87MG that
      expresses wild-type p53 protein, and U251MG which expresses mutant p53.
      Proliferation was investigated by MTT assay, migration by wound-healing migration
      assay and invasion by in vitro transwell Matrigel invasion assay. An IL-1beta
      microenvironment significantly increased migration and invasion of both wild-type
      and mutant p53 expressing glioma cells, but significantly increased proliferation
      only in U87MG glioma cells. These effects were inhibited by IL-1 receptor
      antagonist (IL-1Ra), thus giving evidence that an IL-1beta milieu promotes glioma
      cell migration, invasion, and proliferation.

PMID- 25053169
TI  - Counselling about HIV serological status disclosure: nursing practice or law
      enforcement? a Foucauldian reflection.
AB  - Recently, focus groups and qualitative interviews with nurses who provide
      frontline care for persons living with HIV highlighted the contentiousness
      surrounding the seemingly innocuous activity of counselling clients about HIV
      status disclosure, hereafter disclosure counselling. These empirical studies
      highlighted that while some nurses felt they should instruct clients to disclose
      their HIV-positive status if HIV transmission were possible, other nurses were
      equally adamant that such counselling was outside the nursing scope of practice.
      A review of these opposing perceptions about disclosure counselling, including an
      examination of the empirical evidence which supports each point, revealed that
      the dichotomous arguments needed to be nuanced. The empirical evidence about
      serostatus disclosure neither supported nor refuted either of these assertions;
      rather, it substantiated parts of each. To create this understanding, both
      empirical and theoretical works are used. First, the results of empirical studies
      about serostatus disclosure, or lack thereof and HIV transmission is presented;
      as part of this, Marks and Crepaz's HIV disclosure and exposure framework is
      examined. Second, the work of Michel Foucault on disciplinary and pastoral power
      is drawn from. The outcome is a nuanced understanding about the
      interrelationships between disclosure counselling and nursing practice and a
      final interpretation about what this understanding means for public health
      practice. 

PMID- 25053170
TI  - In silico screening of antifolate based novel inhibitors from Brucea mollis Wall.
      ex kurz against quadruple mutant drug resistant PfDHFR.
AB  - Plasmodium falciparum is the most lethal form of the genus Plasmodium which
      causes malaria, a 'disease of antiquity'. Globally it affects the health and
      socio-economic development of a large population especially in Sub-Saharan Africa
      and Southeast Asia. The Plasmodium falciparum dihydrofolate reductase-thymidylate
      synthase (PfDHFR-TS) is an important target of antimalarial drugs. Mutations at
      the active site of PfDHFR have resulted in decrease drug binding affinity of DHFR
      inhibitors. In the present study we selected ten compounds of Brucea mollis Wall.
      Ex kurz and checked for their drug likeness using various computational tools and
      potential interactions with PfDHFR by molecular docking study. Soulameanone, a
      quassinoid of Brucea mollis Wall. Ex kurz showed better binding affinity when
      compared to pyrimethamine for both wild and quadruple mutant drug resistant
      PfDHFR. In addition, similar isomers of soulameanone were screened for their drug
      likeness and to study their interactions with PfDHFR. Twenty three compounds
      showed better binding affinity compared to soulameanone. 

PMID- 25053171
TI  - Triple antibiotic combination therapy may improve but not resolve granuloma
      annulare.
AB  - Granuloma annulare is a fairly common entity yet lacks reliable treatment options
      especially when multiple lesions or dissemination exists. A recent case series
      suggests that a regimen of three oral antibiotics may prove to be an effective
      treatment. Our objective is to evaluate the efficacy of once monthly triple
      antibiotic therapy for granuloma annulare. We conducted an open-label prospective
      study of subjects with at least five lesions of granuloma annulare who received
      once monthly rifampin, ofloxacin, and minocycline for 6 months. Improvement was
      measured with a novel objective Granuloma Annulare Severity Index (GASI) scoring
      system. Twenty-one subjects enrolled. Ten subjects (48%) achieved at least a 50%
      reduction in their GASI, including three subjects (14%) who reached 75%
      improvement and one subject (5%) whose skin cleared. Six subjects (29%) had no
      change or worsening of their granuloma annulare. Median GASI scores decreased
      significantly by 15 points (p < 0.01), although the clinical significance of this
      result is unclear. As this was a small open-label study without a control group,
      we cannot determine if the results simply reflect the natural course of the
      disease. The GASI is not a validated assessment tool. Once monthly triple
      antibiotic use may improve but not clear granuloma annulare over 6 months.
      Randomized trials may be warranted to further assess this therapy.

PMID- 25053172
TI  - Biosynthesis and characterization of silver nanoparticles produced by Pleurotus
      ostreatus and their anticandidal and anticancer activities.
AB  - The biosynthesis of nanoparticles has received increasing interest because of the
      growing need to develop safe, cost-effective and environmentally friendly
      technologies for the synthesis of nano-materials. In this study, silver
      nanoparticles (AgNPs) were synthesized using a reduction of aqueous Ag(+) ions
      with culture supernatant from Pleurotus ostreatus. The bioreduction of AgNPs was
      monitored by ultra violet-visible spectroscopy and the obtained AgNPs were
      characterized by transmission electron microscopy (TEM) and Fourier transform
      infrared spectroscopy techniques. TEM studies showed the size of the AgNPs to be
      in the range of 4-15 nm. The formation of AgNPs might be an enzyme-mediated
      extracellular reaction process. Furthermore, the antifungal effect of AgNPs
      against Candida albicans as compared with commercially antifungal drugs was
      examined. The effect of AgNPs on dimorphic transition of C. albicans was tested.
      The anticancer properties of AgNPs against cells (MCF-7) were also evaluated.
      AgNPs caused a significant decrease in cell viability of an MCF-7 cell line
      (breast carcinoma). Exposure of MCF-7 cells with AgNPs resulted in a dose
      dependent increase in cell growth inhibition varying from 5 to 78 % at
      concentrations in the range of 10-640 MUg ml(-1). The present study demonstrated
      that AgNPs have potent antifungal, antidimorphic, and anticancer activities. The
      current research opens a new avenue for the green synthesis of nano-materials.

PMID- 25053175
TI  - Fabrication of a photocontrolled surface with switchable wettability based on
      host-guest inclusion complexation and protein resistance.
AB  - A novel surface-modification strategy has been developed for the construction of
      a photocontrolled silicon wafer surface with switchable wettability based on host
      guest inclusion complexation. The silicon wafer was first modified by guest
      molecule azobenzene (Azo) via a silanization reaction. Subsequently, a series of
      polymers with different polarities were attached to host molecule beta
      cyclodextrin (beta-CD) to prepare beta-CD-containing hemitelechelic polymers via
      click chemistry. Finally, a photocontrolled silicon wafer surface modified with
      polymers was fabricated by inclusion complexation between beta-CD and Azo, and
      the surface properties of the substrate are dependent on the polymers we used.
      The elemental composition, surface morphology, and hydrophilic/hydrophobic
      property of the modified surfaces were characterized by X-ray photoelectron
      spectroscopy (XPS), atomic force microscope, and contact angle measurements,
      respectively. The antifouling property of the PEG-functionalized surface was
      evaluated by a protein adsorption assay using bovine serum albumin, which was
      also characterized by XPS. The results demonstrate that the surface modified with
      PEG possesses good protein-resistant properties. 

PMID- 25053173
TI  - Dyadic Associations Between Physical Activity and Depressive Symptoms in Older
      Adults with Musculoskeletal Conditions and Their Spouses.
AB  - This study examined the association between physical activity of older
      individuals with musculoskeletal conditions (IMCs) and their spouses' physical
      activity, how physical activity related to one's own and one's partner's
      depressive symptoms, and whether the similarity of partners' physical activity
      related to each partner's depressive symptoms using the actor-partner
      interdependence model. Seventy-seven dyads completed self-report measures of
      physical activity, depressive symptoms and potential covariates (socio
      demographics, physical health conditions and marital satisfaction; IMCs'
      functional impairment and pain; and spouses' support-related stress). As
      hypothesized, we found a positive association between the IMC's and the spouse's
      physical activity. Also, spouses had more depressive symptoms when IMCs engaged
      in less physical activity. However, for both partners, one's own physical
      activity was not significantly associated with one's own depressive symptoms. The
      spouse's physical activity was also not significantly associated with the IMC's
      depressive symptoms, and the similarity between partners' physical activity did
      not significantly relate to either partner's depressive symptoms. Our findings
      suggest that interventions that help increase the physical activity of both
      partners, but particularly IMCs, may benefit spouses' well-being. Copyright (c)
      2014 John Wiley & Sons, Ltd. 

PMID- 25053174
TI  - The role of olfactory challenge tests in incipient dementia and clinical trial
      design.
AB  - The brain changes associated with Alzheimer's disease (AD) develop slowly over
      many years before the onset of dementia. Biomarkers for AD that allow its
      detection during this clinically silent phase will be hugely important when
      disease-modifying treatments that halt or slow its progression become available.
      Early detection, leading to early treatment, may in some cases avert dementia.
      Biomarkers aid our understanding of the presymptomatic stages of the disease and
      enable the identification of individuals with early disease who, by participating
      in clinical trials of investigational treatments with disease-modifying
      potential, contribute unique and vital information necessary to evaluate novel
      therapies. Most currently available AD biomarkers are expensive and not widely
      available and there are major efforts underway to find cheaper, simpler options.
      The olfactory system is affected by AD and the results from simple and
      inexpensive tests of the sense of smell, especially when paired with other
      information, can help identify individuals early in the disease. We review recent
      literature relevant to the use of simple olfactory tests, including some novel
      approaches, as aids to the early detection of AD. We consider their possible role
      in the design and conduct of clinical trials and suggest how in the future, when
      more effective treatments become available, they might be integrated into
      screening programs for early AD detection. 

PMID- 25053176
TI  - Cerebral glucose hypometabolism is associated with mitochondrial dysfunction in
      patients with intractable epilepsy and cortical dysplasia.
AB  - OBJECTIVES: Metabolic imaging studies, such as positron emission tomography
      (PET), allow for an assessment of physiologic functioning of the brain, and
      [(18)F]fluoro-2-deoxyglucose (FDG)-PET is now a commonly used technique in
      presurgical epilepsy evaluations. Focal interictal decreases in glucose
      consumption are often but inconsistently concordant with the ictal onset area,
      and the underlying mechanisms are poorly understood. The current study tests the
      hypothesis that areas of glucose hypometabolism, determined by FDG-PET, are
      associated with mitochondrial dysfunction in patients with medically intractable
      epilepsy associated with isolated focal cortical dysplasia (FCD). METHODS:
      Measures of electron transport chain (ETC) functioning and mitochondrial
      abnormalities (ETC complex biochemistry, protein kinase B subtype 1 (Akt1), glial
      fibrillary acidic protein (GFAP)) were assessed in surgical resection specimens
      that had hypometabolic abnormalities and those that were normal on FDG-PET.
      Determination of FDG-PET abnormalities was based on coregistration of statistical
      parametric mapping (SPM) results with postsurgical images. RESULTS: Twenty-two
      patients (11 male, 11 female; mean age at the time of surgery 10.5 +/- 4.4
      years), with pathologically confirmed FCD, were included in this retrospective
      review. Complex IV function was found to be significantly reduced in areas of
      hypometabolism (p = 0.014), whereas there was a trend toward a significant
      reduction in complex II and III function in areas of hypometabolism (p = 0.08, p
      = 0.059, respectively). These decreases were independent of cortical dysplasia
      severity (p = 0.321) and other clinical epilepsy measures. SIGNIFICANCE: This
      study suggests an association between glucose hypometabolism and reduced
      mitochondrial complex IV functioning, which is independent of the degree of
      cortical dysplasia. This supports the role of cellular energy failure as a
      potential mechanism for intractable epilepsy.

PMID- 25053177
TI  - Inhibition of glioma progression by a newly discovered CD38 inhibitor.
AB  - Glioma, the most common cancer of the central nervous system, has very poor
      prognosis and no effective treatment. It has been shown that activated
      microglia/macrophages in the glioma tumor microenvironment support progression.
      Hence, inhibition of the supporting effect of these cells may constitute a useful
      therapeutic approach. Recently, using a syngeneic mouse glioma progression model,
      we showed that the ectoenzyme CD38 regulated microglia activation and, in
      addition, that the loss of CD38 from the tumor microenvironment attenuated glioma
      progression and prolonged the life span of the tumor-bearing mice. These studies,
      which employed wild-type (WT) and Cd38(-/-) C57BL/6J mice, suggest that
      inhibition of CD38 in glioma microenvironment may be used as a new therapeutic
      approach to treat glioma. Our study tested this hypothesis. Initially, we found
      that the natural anthranoid, 4,5-dihydroxyanthraquinone-2-carboxylic acid
      (rhein), and its highly water-soluble tri-potassium salt form (K-rhein) are
      inhibitors of CD38 enzymatic (nicotinamide adenine dinucleotide glycohydrolase)
      activity (IC50 = 1.24 and 0.84 MUM, respectively, for recombinant mouse CD38).
      Treatment of WT, but not Cd38(-/-) microglia with rhein and K-rhein inhibited
      microglia activation features known to be regulated by CD38
      (lipopolysaccharide/IFN-gamma-induced activation, induced cell death and NO
      production). Furthermore, nasal administration of K-rhein into WT, but not Cd38(
      /-) C57BL/6J, mice intracranially injected with GL261 cells substantially and
      significantly inhibited glioma progression. Hence, these results serve as a proof
      of concept, demonstrating that targeting CD38 at the tumor microenvironment by
      small-molecule inhibitors of CD38, for example, K-rhein, may serve as a useful
      therapeutic approach to treat glioma. 

PMID- 25053178
TI  - Clinical activity of enzalutamide versus docetaxel in men with castration
      resistant prostate cancer progressing after abiraterone.
AB  - BACKGROUND: The optimal sequencing of the multiple active agents now available
      for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior
      reports have suggested diminished responses to sequential lines of androgen
      receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane
      based chemotherapy may be more effective than sequential AR-targeting treatment.
      We sought to evaluate the clinical activity of enzalutamide versus docetaxel in
      men with mCRPC who progressed on abiraterone. METHODS: We performed a single
      institution retrospective analysis of consecutive mCRPC patients who had
      progressed on abiraterone therapy and subsequently received either enzalutamide
      (n=30) or docetaxel (n=31). We evaluated clinical outcomes including prostate
      specific antigen decline of >30% (PSA30) or >50% (PSA50), PSA-progression-free
      survival (PSA-PFS), and clinical/radiographic PFS. We performed multivariable
      modeling to control for baseline and on-treatment differences between groups.
      RESULTS: Compared to subjects who received enzalutamide post-abiraterone,
      subjects who received docetaxel post-abiraterone had more bone metastases, more
      visceral metastases, higher baseline PSA, and had more frequent PSA tests while
      on-treatment. There were no significant differences in PSA30 (41% for
      enzalutamide vs. 53% for docetaxel) or PSA50 (34% vs. 40%) response rates between
      the two groups; there remained no difference after stratifying by
      presence/absence of prior response to abiraterone. Median PSA-PFS was 4.1 versus
      4.1 months for the enzalutamide and docetaxel cohorts, respectively (HR 1.35, 95%
      CI, 0.53-3.66, P=0.502). Median PFS was 4.7 versus 4.4 months, respectively (HR
      1.44, 95% CI, 0.77-2.71, P=0.257). PSA-PFS and PFS did not differ after
      stratifying by prior response to abiraterone. In multivariable analyses, there
      were no significant differences in PSA-PFS or PFS between the two groups.
      CONCLUSIONS: Treatment with either enzalutamide or docetaxel produced modest PSA
      responses and PFS intervals in this abiraterone-pretreated mCRPC population. In
      this retrospective study with small sample size, no significant differences in
      outcomes were observed between groups. Therefore, either enzalutamide or
      docetaxel may be a reasonable option in men who have progressed on abiraterone.

PMID- 25053179
TI  - Quantification of the ambident electrophilicities of halogen-substituted
      quinones.
AB  - Kinetics and mechanisms of the reactions of p-quinone, 2,5-dichloro-p-quinone,
      2,3,4,5-tetrachloro-p-quinone (chloranil), 2,3,4,5-tetrafluoro-p-quinone
      (fluoranil), and 3,4,5,6-tetrachloro-o-quinone with pi-nucleophiles
      (siloxyalkenes, enamines) and amines have been investigated. Products arising
      from nucleophilic attack at all conceivable sites, that is, at C and O of the
      carbonyl groups (pathways a, b) as well as at halogenated and nonhalogenated
      conjugate positions (pathways c, d), were observed. The partial rate constants
      for the C-attack pathways (a, c, d), which are derived from the photometrically
      determined second-order rate constants and the product ratios followed the linear
      free energy relationship log k (20  degrees C) = sN(E + N) ( Mayr , H.; J. Am.
      Chem. Soc. 2001 , 123 , 9500 - 9512 ). It was, therefore, possible to calculate
      the electrophilicity parameters E of the different positions of the quinones from
      log k (20  degrees C) and the N and sN parameters of the nucleophilic reaction
      partners, which have previously been derived from their reactions with
      benzhydrylium ions. Almost all rate constants for the C-attack pathways (a, c, d)
      were considerably larger than those calculated for the corresponding SET
      processes, indicating the operation of polar mechanisms. SET mechanisms may only
      account for the formation of the products formed via O-attack. With the E
      parameters determined in this work, it is now possible to predict rate constants
      for the reactions of these quinones with a large variety of nucleophiles and,
      thus, envisage unprecedented reactions of quinones.

PMID- 25053182
TI  - The effects of levosimendan on renal function early after heart transplantation:
      results from a pilot randomized trial.
AB  - BACKGROUND: We evaluated the effects of a levosimendan (LS)-based strategy
      compared with standard inotropic therapy on renal function in heart
      transplantation. METHODS AND RESULTS: Using a randomized study design, 94
      patients were assigned to LS-based therapy or standard inotropic support. At the
      time of transplantation, the groups did not differ in age, gender, heart failure
      etiology, hemodynamic profile, LVEF, or comorbidities. While there were no
      differences in serum creatinine (sCr) or eGFR between groups at baseline,
      patients in the LS group had a greater increase in their relative eGFR (62% vs.
      12%, p = 0.002) and a lower incidence of acute kidney injury (AKI) (28% vs. 6%, p
      = 0.01) during the first post-transplant week. On logistic regression analysis,
      correlates of AKI were randomization to LS therapy (OR = 0.21 [0.09-0.62], p =
      0.01), baseline renal dysfunction (OR = 3.9 [1.1-13.6], p = 0.032), and diabetes
      mellitus (OR = 4.2 [1.1-16.5], p = 0.038). However, LS was associated with a
      greater need for additional norepinephrine therapy (40 [85%] vs. 15 [31%], p <
      0.001) and a trend toward longer intensive care unit stay (9.5 +/- 9.0 d vs. 7.0
      +/- 6.0 d, p = 0.13). CONCLUSIONS: In patients undergoing heart transplantation,
      levosimendan-based strategy may be associated with better renal function when
      compared to standard therapy.

PMID- 25053180
TI  - The Robertsonian phenomenon in the house mouse: mutation, meiosis and speciation.
AB  - Many different chromosomal races with reduced chromosome number due to the
      presence of Robertsonian fusion metacentrics have been described in western
      Europe and northern Africa, within the distribution area of the western house
      mouse Mus musculus domesticus. This subspecies of house mouse has become the
      ideal model for studies to elucidate the processes of chromosome mutation and
      fixation that lead to the formation of chromosomal races and for studies on the
      impact of chromosome heterozygosities on reproductive isolation and speciation.
      In this review, we briefly describe the history of the discovery of the first and
      subsequent metacentric races in house mice; then, we focus on the molecular
      composition of the centromeric regions involved in chromosome fusion to examine
      the molecular characteristics that may explain the great variability of the
      karyotype that house mice show. The influence that metacentrics exert on the
      nuclear architecture of the male meiocytes and the consequences on meiotic
      progression are described to illustrate the impact that chromosomal
      heterozygosities exert on fertility of house mice-of relevance to reproductive
      isolation and speciation. The evolutionary significance of the Robertsonian
      phenomenon in the house mouse is discussed in the final section of this review.

PMID- 25053183
TI  - HIPAA compliance from a private practice purview.

PMID- 25053181
TI  - Losing control under ketamine: suppressed cortico-hippocampal drive following
      acute ketamine in rats.
AB  - Systemic doses of the psychotomimetic ketamine alter the spectral characteristics
      of hippocampal and prefrontal cortical network activity. Using dynamic causal
      modeling (DCM) of cross-spectral densities, we quantify the putative synaptic
      mechanisms underlying ketamine effects in terms of changes in directed, effective
      connectivity between dorsal hippocampus and medial prefrontal (dCA1-mPFC) cortex
      of freely moving rats. We parameterize dose-dependent changes in spectral
      signatures of dCA1-mPFC local field potential recordings, using neural mass
      models of glutamatergic and GABAergic circuits. Optimizing DCMs of theta and
      gamma frequency range responses, model comparisons suggest that both enhanced
      gamma and depressed theta power result from a reduction in top-down connectivity
      from mPFC to the hippocampus, mediated by postsynaptic NMDA receptors (NMDARs).
      This is accompanied by an alteration in the bottom-up pathway from dCA1 to mPFC,
      which exhibits a distinct asymmetry: here, feed-forward drive at AMPA receptors
      increases in the presence of decreased NMDAR-mediated inputs. Setting these
      findings in the context of predictive coding suggests that NMDAR antagonism by
      ketamine in recurrent hierarchical networks may result in the failure of top-down
      connections from higher cortical regions to signal predictions to lower regions
      in the hierarchy, which consequently fail to respond consistently to errors.
      Given that NMDAR dysfunction has a central role in pathophysiological theories of
      schizophrenia and that theta and gamma rhythm abnormalities are evident in
      schizophrenic patients, the approach followed here may furnish a framework for
      the study of aberrant hierarchical message passing (of prediction errors) in
      schizophrenia-and the false perceptual inferences that ensue. 

PMID- 25053184
TI  - Habitual yogurt consumption and health-related quality of life: a prospective
      cohort study.
AB  - BACKGROUND: Health-related quality of life (HRQL) is a global indicator of
      perceived health status, which includes physical and mental domains. Several
      biological mechanisms might support an association between consumption of yogurt
      and better HRQL. OBJECTIVE: Our aim was to assess the association between
      habitual yogurt consumption and HRQL in the general adult population. DESIGN: We
      conducted a prospective study with 4,445 individuals aged 18 years and older who
      were recruited in 2008 to 2010 and were followed up to 2012. Habitual yogurt
      consumption was assessed at baseline with a validated diet history. HRQL was
      measured with the Physical Composite Summary and the Mental Composite Summary of
      the Spanish version of the SF-12 Health Survey. The analysis of the association
      between baseline yogurt consumption and HRQL at 2012 was performed with linear
      regression and adjusted for the main confounders, including baseline HRQL.
      RESULTS: Mean follow-up was 3.5 years (standard deviation=0.6 years). Compared
      with nonconsumers of yogurt, the Physical Composite Summary scores were similar
      in habitual consumers of <=6 servings/week (beta=.40; P=0.20) and in consumers of
      >=1 serving/day (beta=.25; P=0.45). A suggestion of tendency toward a lower
      Mental Composite Summary score was found among daily yogurt consumers (beta=-.65;
      P=0.09; P for trend across categories=0.07). Results were similar among
      individuals without morbidity, never smokers, and individuals with higher
      adherence to the Mediterranean diet. CONCLUSIONS: Habitual yogurt consumption did
      not show an association with improved HRQL.

PMID- 25053186
TI  - The Rintala flap: a versatile procedure for nasal reconstruction.
AB  - INTRODUCTION: For the nasal reconstruction, local flap using the adjacent tissue
      is selected from an esthetic viewpoint. The Rintala flap is a useful option, and
      reconstruction of the glabellar over the nasal tip with this flap is ideal, for
      which the procedure was modified to increase the blood flow to the Rintala flap
      to extend its clinical applications. METHODS: For defects of the glabellar over
      the middle one third of nasal dorsum, the Rintala flap is transferred employing
      the original design and technique dissected on supraperiosteal plane. For defects
      of the lower one third of nasal dorsum over the nasal tip, blood supply through
      the lateral nasal artery is added to the distal end of the flap, preparing a long
      flap with stable blood supply like Maruyama described in 1997. RESULTS: This
      procedure was applied for nasal reconstruction in 15 patients. The Rintala flap
      was applied in 12 and the modified Rintala flap with adding blood flow from the
      lateral nasal artery was applied in 3. Blood supply to the flap was very stable
      in all patients, and favorable outcomes were achieved. CONCLUSIONS: Using this
      procedure, the natural contour and morphology of the glabellar over the nasal tip
      may be reconstructed. The technique is simple and easy. Using this procedure,
      clinical applications of the Rintala flap can be extended, showing that it is a
      useful nasal reconstructive procedure.

PMID- 25053185
TI  - Differential expression and localization of ADAM10 and ADAM17 during rat
      spermatogenesis suggest a role in germ cell differentiation.
AB  - BACKGROUND: Extracellular metolloproteases have been implied in different process
      such as cell death, differentiation and migration. Membrane-bound
      metalloproteases of the ADAM family shed the extracellular domain of many
      cytokines and receptor controlling auto and para/juxtacrine cell signaling in
      different tissues. ADAM17 and ADAM10 are two members of this family surface
      metalloproteases involved in germ cell apoptosis during the first wave of
      spermatogenesis in the rat, but they have other signaling functions in somatic
      tissues. RESULTS: In an attempt to further study these two enzymes, we describe
      the presence and localization in adult male rats. Results showed that both
      enzymes are detected in germ and Sertoli cells during all the stages of
      spermatogenesis. Interestingly their protein levels and cell surface localization
      in adult rats were stage-specific, suggesting activation of these enzymes at
      particular events of rat spermatogenesis. CONCLUSIONS: Therefore, these results
      show that ADAM10 and ADAM17 protein levels and subcellular (cell surface)
      localization are regulated during rat spermatogenesis.

PMID- 25053187
TI  - Comparison of Pb, Zn, Cd, As, Cr, Mo and Sb adsorption onto natural surface
      coatings in a stream draining natural as geochemical anomaly.
AB  - Natural surface coatings (biofilms) were collected on glass slides in the
      shallow, arsenic-rich stream and were used to compare biofilm trace element
      adsorption properties. Biofilm element retention and affinities were element
      specific indicating different processes control their sequestration. Distribution
      coefficients (K d values), calculated as the ratio between biofilm and dissolved
      trace element concentrations, revealed solid phase enrichment that, depending on
      the trace element, extended from 10(0.18) to 10(3.17). Elements were specifically
      scavenged by the organic constituents of the biofilm itself (Fe, Pb, Zn, Cr) and
      associated biominerals of poorly ordered Mn oxide (Cd, As, Mo, Sb). The results
      provide an evidence for the significant role that microbial activity can play in
      trace element geochemistry in freshwater environment. 

PMID- 25053188
TI  - A 3-year cohort study of the natural history of spinocerebellar ataxia type 6 in
      Japan.
AB  - BACKGROUND: Only a few prospective studies have determined which clinical
      symptoms and factors are associated with the disease severity of spinocerebellar
      ataxia type 6 (SCA6). A multicenter longitudinal cohort study was conducted to
      clarify both the natural history of SCA6 in Japan and the factors influencing
      disease progression. METHODS: Patients were consecutively recruited between 2007
      and 2008. Scores from the Scale for the Assessment and Rating of Ataxia (SARA)
      and Barthel Index (BI) were collected prospectively each year. Additionally, data
      from the Japan intractable diseases research (IDR) registry were collected both
      retrospectively, from 2003 to 2006, and prospectively, from 2007 to 2010. As a
      result, we were able to collect 3 years of retrospective data and 4 years of
      prospective data during the course of 3 yearly visits. RESULTS: Forty-six
      patients were registered. The follow-up rate of the third year was 93%. The SARA
      scores worsened significantly each year. Over 3 years, the decline of the SARA
      scores was 1.33 +/- 1.40 points/year. The results of multivariate analysis of the
      decline of the SARA score were not significant. The IDR scores correlated well
      with the SARA and BI scores. Kaplan-Meier curves of 7 years of data from the IDR
      registry illustrated the correlation between the ability to walk and the time
      course of the disease. CONCLUSIONS: Information regarding the progression of
      ataxia and the decline in the activities of daily living (ADL) in patients with
      SCA6 was obtained by a 3-year cohort study and a 7-year IDR study. The decline of
      the SARA score of patients with SCA6 was 1.33 +/- 1.40 points/year. The results
      elucidate the natural history of SCA6, factors influencing disease severity, and
      utility of data from the IDR registry of Japan.

PMID- 25053189
TI  - ESR dating of the Majuangou and Banshan Paleolithic sites in the Nihewan Basin,
      North China.
AB  - The fluvio-lacustrine sequences in the Nihewan Basin, northern China provide an
      important source of Paleolithic settlements and therefore early human occupation
      in the eastern Old World. Here we present electron spin resonance (ESR)
      chronology for the Majuangou (MJG-III, MJG-II and MJG-I) and Banshan (BS)
      Paleolithic sites in this basin by the quartz Ti-Li center ESR dating. Results
      show that the ages of MJG-III and MJG-II could be estimated to be ~1.70 Ma
      (millions of years ago); of MJG-I, ~1.40 Ma; and BS, ~1.35 Ma. This ESR
      chronology is consistent with the previous magnetochronology, thus providing
      strong support for the earliest human presence at the high northern latitudes of
      Northeast Asia. 

PMID- 25053190
TI  - Mental health and Victorian Aboriginal people: what can data mining tell us?
AB  - Nationally, Aboriginal people experience high levels of psychological distress,
      primarily due to trauma from colonisation. In Victoria, Aboriginal Community
      Controlled Health Organisations (ACCHOs) provide many services to support mental
      health. The aim of the present study was to improve understanding about Victorian
      Aboriginal people and mental health service patterns. We located four mental
      health administrative datasets to analyse descriptively, including Practice
      Health Atlas, Alcohol and Other Drug Treatment Service (AODTS), Kids Helpline and
      Close The Gap Pharmaceutical Scheme data. A large proportion of the local
      Aboriginal population (70%) were regular ACCHO clients; of these, 21% had a
      mental health diagnosis and, of these, 23% had a Medicare Mental Health Care Plan
      (MHCP). There were higher rates of Medicare MHCP completion rates where general
      practitioners (GPs) had mental health training and the local Area Mental Health
      Service had a Koori Mental Health Liaison Officer. There was an over
      representation of AODTS episodes, and referrals for these episodes were more
      likely to come through community, corrections and justice services than for non
      Aboriginal people. Aboriginal episodes were less likely to have been referred by
      a GP or police and less likely to have been referrals to community-based or home
      based treatment. There was an over-representation of Victorian Aboriginal calls
      to Kids Helpline, and these were frequently for suicide and self-harm reasons. We
      recommend primary care mental health programs include quality audits, GP
      training, non-pharmaceutical options and partnerships. Access to appropriate
      AODTS is needed, particularly given links to high incarcerations rates. To ensure
      access to mental health services, improved understanding of mental health service
      participation and outcomes, including suicide prevention services for young
      people, is needed. 

PMID- 25053191
TI  - Characteristics associated with intervention and follow-up attendance in a
      secondhand smoke exposure study for families of NICU infants.
AB  - OBJECTIVE: The neonatal intensive care unit (NICU) is an ideal setting to
      intervene with an under served population on secondhand smoke exposure (SHSe).
      Unfortunately, attrition may compromise outcomes. Baseline characteristics
      associated with intervention and follow-up attendance were investigated in
      mothers who participated in a novel SHSe prevention study designed for households
      with a smoker and a NICU-admitted infant. METHODS: Intervention participants
      received two motivational, NICU-based counseling sessions; usual care
      participants received pamphlets. Home-based follow-up assessments occurred at 1,
      3 and 6 months. Sociodemographic, smoking history, and psychosocial factors were
      analyzed. RESULTS: Mothers from households with greater numbers of cigarettes
      smoked and fewer children had higher odds of both intervention and follow-up
      attendance. Maternal smoking abstinence (lifetime), more adults in the home and
      higher perceived interpersonal support were also associated with higher odds of
      follow-up visit completion. CONCLUSIONS: Innovative strategies are needed to
      engage mothers in secondhand smoke interventions, especially mothers who smoke,
      have lower levels of social support and have greater childcare responsibilities.

PMID- 25053192
TI  - Characteristics of boys with the so-called true undescended testis diagnosed at
      the third postnatal month--a population-based case-control study.
AB  - OBJECTIVE: Undescended testis (cryptorchidism) is a common congenital abnormality
      of male genital organs diagnosed at birth followed with frequent postnatal
      descensus. However, the so-called isolated true undescended testis (ITUT)
      diagnosed at the third postnatal month seems to be an independent defect-entity,
      and this hypothesis was planned to confirm or reject in the study. METHOD: The
      evaluation of birth outcomes and maternal socio-demographic data of cases with
      ITUT in the population-based large dataset of the Hungarian Congenital
      Abnormality Registry. RESULTS: There was a higher rate of preterm birth and
      particularly of low birthweight in 2052 cases with ITUT compared to 24,814
      population male controls without any defects. The rate of twins was not higher in
      cases with older mothers, higher birth order and lower socio-economic status. The
      comparison of data of boys with undescended testis diagnosed at birth found in
      the previous study and with ITUT in this study confirmed our hypothesis.
      CONCLUSIONS: Undescended testis can be differentiated into two subgroups: boys
      with frequent postnatal descensus mainly after preterm delivery and boys with
      ITUT without postnatal testis descensus with frequent intrauterine growth
      restriction, older mothers with higher birth order and low socio-economic status.

PMID- 25053193
TI  - Perinatal antibiotic exposure of neonates in Canada and associated risk factors:
      a population-based study.
AB  - OBJECTIVE: To describe neonatal antibiotic exposures occurring immediately before
      and after birth and their associated risk factors. METHODS: A retrospective
      review of the hospital charts of 449 mother-neonate pairs enrolled in the
      Canadian Healthy Infant Longitudinal Development national birth-cohort study was
      conducted at two tertiary hospitals and one rural hospital in Manitoba, Canada.
      The main outcome measures included the following: maternal and neonatal
      antibiotic use during the perinatal period; indications for antibiotic use,
      including suspected neonatal sepsis, maternal group B Streptococcus (GBS),
      premature rupture of membranes and caesarean-section; maternal health status,
      focusing on gestational hypertension, gestational diabetes, obesity and
      primigravida pregnancies. RESULTS: During the perinatal period, 45.0% of neonates
      were exposed to antibiotics. Intravenous penicillin G (17%) and cefazolin (16%)
      were the most commonly administered intrapartum antibiotics. Colonization with
      GBS was confirmed in 21.2% of women and treated with antibiotics in 86% of cases.
      Overweight women and women with hypertension were significantly more likely to
      receive intrapartum antibiotics for caesarean section or GBS prophylaxis.
      Antibiotic treatment of the neonate was highest following emergency caesarean
      section (12%) or unknown maternal GBS status (20%). CONCLUSIONS: Neonates in
      Canada are routinely exposed to antibiotics during the perinatal period.

PMID- 25053194
TI  - Expression of FK506-binding protein 52 (FKBP52) in chorionic villi with early
      recurrent spontaneous abortion.
AB  - OBJECTIVE: To investigate the mRNA and protein expression of FK506-binding
      protein 52 (FKBP52) in the chorionic villi of patients with recurrent spontaneous
      abortion (RSA) and normal women during early pregnancy. METHODS: Fresh chorionic
      villus tissues were collected from 60 subjects. A total of 30 patients with a
      history of RSA were enrolled into the RSA group and 30 normal pregnant women were
      enrolled into the control group. The FKBP52 mRNA expression levels in chorionic
      villi of the RSA patients and healthy controls were measured via semiquantitative
      RT-PCR. The protein distribution and expression levels of FKBP52 in chorionic
      villi were analyzed through immunohistochemistry (IHC). The correlation between
      FKBP52 expression and RSA was analyzed. RESULTS: We demonstrated that FKBP52 mRNA
      is expressed in chorionic villi samples of normal pregnancy and RSA. RSA patients
      exhibited significantly lower FKBP52 gene expression levels compared with those
      in normal pregnancies (p < 0.05). FKBP52 immunoreactivity in chorionic villi was
      mainly observed in trophoblast cell cytoplasm. The FKBP52 protein expression
      levels in the chorionic villi of RSA patients was significantly lower than in
      normal women during pregnancy (p < 0.05). CONCLUSIONS: FKBP52 protein levels were
      decreased in the chorionic villi of RSA patients, which indicate that the
      decrease in FKBP52 may be associated with RSA. The low FKBP52 mRNA expression
      level, which is consistent with the IHC result, may affect embryonic development
      and even lead to abortion. FKBP52 may be involved in the pathogenesis of RSA and
      new therapies that increase the FKBP52 expression may help treat RSA.

PMID- 25053195
TI  - Placental pathologies on fetal MRI are associated with high impairment rates: a
      prospective long-term outcome study.
AB  - OBJECTIVE: Placental anomalies visualized at midgestation by MRI are shown to be
      related to pregnancy outcome. We performed a prospective cohort study to
      investigate the influence of placental pathologies diagnosed with fetal MRI on
      long-term neurodevelopmental outcome. METHODS: In our hospital-based, cross
      sectional study, all fetal MRI examinations of pregnancies with vascular
      placental pathology (i.e. infarction with/without hemorrhage, subchorionic
      thrombi/hemorrhages, intervillous thrombi/hemorrhages or retroplacental hematoma)
      between 2003 and 2007 were included. The extent of the pathology was expressed as
      the percentage of abnormality related to the whole placental volume.
      Pathohistological reports were correlated to MRI findings. Infants were
      prospectively investigated using Bayley developmental scales at the age of 2-3.5
      years. Impairment was categorized as a Bayley scale two SDs below normal (<85
      points). RESULTS: There were 31 singletons and 25 offspring of multiple
      pregnancies included in the analyses. Impairment rates were 32.2% in singletons
      and 32.0% in multiple births. No correlation between neuro/motor developmental
      outcome at 2-3.5 years and the type, extent or gestational week at the time of
      diagnoses of placental vascular pathologies was found. CONCLUSION: The long-term
      outcome of children with vascular placental pathologies on fetal MRI was
      associated with a high impairment rate after 2-3.5 years, both on motor- and
      neurodevelopmental Bayley scales. Neurological impairment did not correlate with
      the extent of placental involvement, intrauterine growth restriction, gestational
      age at birth or multiple state.

PMID- 25053196
TI  - Influence of threatened miscarriage on pregnancy and early postpartum period: a
      case-control report.
AB  - OBJECTIVE: To evaluate the influence of threatened miscarriage on obstetric
      complications during pregnancy and early postpartum period. METHODS: In this case
      control study, hospital records of 12,050 first-trimester patients between
      January 2011 and December 2012 at the Research and Educational Hospital in
      Ankara, Turkey, were used. Of the 12,050 patients, 481 threatened miscarriage
      patients were evaluated. The control group was formed by age- and body mass index
      matched cases without first trimester bleeding. Abortion, intrauterine foetal
      demise, preterm birth, preeclampsia, antenatal haematoma, uterine atony placental
      abruption and low birth-weights were compared between the study and the control
      group. RESULTS: When compared with the control group, the risk of having a
      preterm birth (p = 0.014; OR: 1.95; 95% CI: 1.15-3.24), low-birth-weight infant
      (p = 0.001; OR: 2.33; 95% CI: 1.45-3.83) and abortion (p = 0.00; OR: 2.55; 95%
      CI: 1.62-3.91) increased in cases of threatened miscarriage. However, the risk of
      uterine atony was decreased (p = 0.006; OR: 0.09; 95% CI: 0.12-0.7) in the
      threatened miscarriage group when compared with the control group. Threatened
      miscarriage did not increase the risk of placenta praevia, placental abruption or
      intrauterine foetal demise. CONCLUSION: Increased complications after threatened
      miscarriage is probably due to the persistence of a triggering mechanism. As
      preterm birth and abortion rate increased, whilst uterine atony rate decreased,
      one of the mechanisms causing threatened miscarriage might be increased uterine
      contractility.

PMID- 25053197
TI  - Upper limit of cancer extent on biopsy defining very low-risk prostate cancer.
AB  - OBJECTIVE: To investigate how much Gleason pattern 3 cancer prostate biopsy
      specimens may contain without an increased risk of undetected more aggressive
      cancer, compared with the risk for cancers fulfilling the National Comprehensive
      Cancer Network (NCCN) criteria for very low-risk prostate cancer. PATIENTS AND
      METHODS: We identified 1286 men aged <70 years in the National Prostate Cancer
      Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c
      or T2 prostate cancer with Gleason pattern <=3 only, prostate-specific antigen
      (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association
      between the extent of cancer in the biopsies (the number and proportion of
      positive cores and the total cancer length in the cores in millimetres) and the
      likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic
      regression. RESULTS: In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in
      the RP specimen. Increasing number and proportion of positive biopsy cores, as
      well as increasing biopsy cancer length were both significantly associated with
      increased risk of upgrading at RP in univariable analysis, but in multivariable
      analysis only biopsy cancer length remained significant. The 684 men with stage
      T1c and <8 mm cancer had similar risk of upgrading regardless of whether the
      number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was
      more common among the remaining men (40%, P < 0.01). CONCLUSIONS: Men aged <70
      years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3
      are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1
      2 cores with cancer, provided that the total biopsy cancer length is <8 mm. We
      propose that the definition of very low-risk prostate cancer is widened
      accordingly.

PMID- 25053198
TI  - Impact of differently modified nanocrystalline diamond on the growth of
      neuroblastoma cells.
AB  - The aim of this study was to assess the impact of nanocrystalline diamond (NCD)
      thin coatings on neural cell adhesion and proliferation. NCD was fabricated on
      fused silica substrates by microwave plasma chemical vapor deposition (MPCVD)
      method. Different surface terminations were performed through exposure to
      reactive hydrogen and by UV induced oxidation during ozone treatment. Boron doped
      NCD coatings were also prepared and investigated. NCD surface wettability was
      determined by contact angle measurement. To assess biocompatibility of the NCD
      coatings, the neuroblastoma SH-SY5Y cell line was used. Cells were plated
      directly onto diamond surfaces and cultured in medium with or without fetal
      bovine serum (FBS), in order to evaluate the ability of cells to adhere and to
      proliferate. The obtained results showed that these cells adhered and
      proliferated better on NCD surfaces than on the bare fused silica. The cell
      proliferation on NCD in medium with and without FBS after 48h from plating was on
      average, respectively, 20 and 58% higher than that on fused silica, irrespective
      of NCD surface modification. Our results showed that the hydrogenated, oxygenated
      and boron-doped NCD coatings can be used for biomedical purposes, especially
      where good optical transparency is required. 

PMID- 25053199
TI  - Associations between physical inactivity and sedentary behaviors among
      adolescents in 10 cities in China.
AB  - BACKGROUND: Studies in western countries have revealed that excessive sedentary
      behavior is a major risk factor for physical inactivity in adolescents. This
      study was performed to investigate the association between sedentary behavior and
      physical inactivity in Chinese adolescents using a large-scale cross-sectional
      survey design. METHODS: This study was part of the 2011 Chinese Youth Risk
      Behavior Survey. Between March and September 2011, 10,214 11-18-year-olds were
      recruited for survey participation in 18 schools in 10 cities in China.
      Demographic and socioeconomic characteristics, and the prevalences of physical
      inactivity and sedentary behaviors, were examined. Correlations between sedentary
      behavior and physical inactivity were analyzed using baseline logistic
      regression. RESULTS: Among the final 9,901 students, physical inactivity (~80%)
      and sedentary behaviors (television viewing, 43%; computer use, 30.2%) were
      prevalent. More male than female students reported sedentary behaviors
      (television viewing > 2 h: 5.5% vs. 3.9%; computer use > 2 h: 7.2% vs. 3.5%; both
      p < 0.05), but more males were physically active than females (25.1% vs.14.6%; p
      < 0.05). Television viewing was associated with lower odds of no physical
      activity (No PA) in males [0-2 h: adjusted odds ratio (AOR) = 0.81, 95%
      confidence interval (CI) = 0.68-0.96; >4 h: OR = 0.34, 95% CI = 0.18-0.64], but
      not in females. A similar pattern between insufficient physical activity and >4 h
      TV viewing (AOR = 0.42, 95% CI = 0.23-0.76) and >4 h computer use (AOR = 0.49,
      95% CI = 0.30-0.78) was observed in males. In females, 0-2 h daily computer use
      was associated with higher odds of physical inactivity (No PA: AOR = 1.42, 95% CI
      = 1.10-1.82; Insufficient PA: AOR = 1.58, 95% CI = 1.24-2.01), while TV viewing
      was not associated with No PA or Insufficient PA. The probability of physical
      inactivity significantly increased with grade and decreased with socioeconomic
      status. CONCLUSIONS: Physical inactivity and sedentary behaviors were prevalent
      in Chinese adolescents. Further support, including parental guidance and the
      provision of publicly accessible facilities, is necessary to encourage Chinese
      youths to engage sufficiently in physical activities.

PMID- 25053200
TI  - Combined neuroimaging and gene expression analysis of the genetic basis of brain
      plasticity indicates across species homology.
AB  - Brain plasticity and memory formation depend on the expression of a large number
      of genes. This relationship had been studied using several experimental
      approaches and researchers have identified genes regulating plasticity through a
      variety of mechanisms. Despite this effort, a great deal remains unknown
      regarding the role of different genes in brain plasticity. Previous studies
      usually focused on specific brain structures and many of the genes influencing
      plasticity have yet to be identified. In this work, we integrate results of in
      vivo neuroimaging studies of plasticity with whole-brain gene expression data for
      the study of neuroplasticity. Brain regions, found in the imaging study to be
      involved in plasticity, are first spatially mapped to the anatomical framework of
      the genetic database. Feature ranking methods are then applied to identify genes
      that are differentially expressed in these regions. We find that many of our
      highly ranked genes are involved in synaptic transmission and that some of these
      genes have been previously associated with learning and memory. We show these
      results to be consistent when applying our method to gene expression data from
      four human subjects. Finally, by performing similar experiments in mice, we
      reveal significant cross species correlation in the ranking of genes. In addition
      to the identification of plasticity related candidate genes, our results also
      demonstrate the potential of data integration approaches as a tool to link high
      level phenomena such as learning and memory to underlying molecular mechanisms.

PMID- 25053201
TI  - Molecular characterization of DHA-1-producing Klebsiella pneumoniae isolates
      collected during a 4-year period in an intensive care unit.
AB  - Seventeen Klebsiella pneumoniae isolates producing DHA-1 beta-lactamase were
      collected in an intensive care unit between 2006 and 2010. Molecular analysis
      revealed the predominance of ST48 and ST1263 clones of K. pneumoniae and the
      spread of DHA-1-encoding plasmids belonging to incompatibility group IncL/M or
      IncHI2. 

PMID- 25053202
TI  - Trend in vancomycin susceptibility and correlation with molecular characteristics
      of methicillin-resistant Staphylococcus aureus causing invasive infections in
      Taiwan: results from the Tigecycline in vitro Surveillance in Taiwan (TIST)
      study, 2006-2010.
AB  - This study was intended to investigate the trend in vancomycin susceptibility and
      correlation with molecular characteristics of methicillin-resistant
      Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA
      isolates were collected from patients with invasive infections as part of
      bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST)
      from 2006 to 2010. MICs of the isolates to vancomycin were determined using the
      agar dilution method. Characteristics of staphylococcal cassette chromosome mec
      (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator
      (agr) of the isolates were identified by polymerase chain reaction methods. MRSA
      isolates with SCCmec types I, II, and III were molecularly defined as hospital
      associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were
      assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates
      exhibited vancomycin MICs <=1 mg/L. A declining trend in vancomycin MICs among
      MRSA isolates was noted, which was associated with the decline in proportion of
      HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010.
      An increase in the geometric mean of vancomycin MICs was found in MRSA with
      particular molecular types such as SCCmec types II and III, agr groups I and II,
      and dru10-14. A significant correlation among particular molecular types was
      found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14,
      SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no
      vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC
      against MRSA was attributed to the increasing prevalence of CA-MRSA over time. 

PMID- 25053203
TI  - Microbiological features of KPC-producing Enterobacter isolates identified in a
      U.S. hospital system.
AB  - Microbiological data regarding Klebsiella pneumoniae carbapenemase (KPC)
      producing Enterobacter spp. are scarce. In this study, 11 unique KPC-producing
      Enterobacter isolates were identified among 44 ertapenem-nonsusceptible
      Enterobacter isolates collected between 2009 and 2013 at a hospital system in
      Western Pennsylvania. All cases were healthcare-associated and occurred in
      medically complex patients. While pulsed-field gel electrophoresis showed diverse
      restriction patterns overall, multilocus sequence typing identified Enterobacter
      cloacae isolates with sequence types 93 and 171 from 2 hospitals each. The levels
      of carbapenem minimum inhibitory concentrations were highly variable. All
      isolates remained susceptible to colistin and tigecycline, and the majority, to
      amikacin and doxycycline. A blaKPC-carrying IncN plasmid conferring trimethoprim
      sulfamethoxazole resistance was identified in 3 of the isolates. Spread of blaKPC
      in Enterobacter spp. appears to be due to a combination of plasmid-mediated and
      clonal processes. 

PMID- 25053204
TI  - Condyloma acuminata in the tongue and palate of a sexually abused child: a case
      report.
AB  - BACKGROUND: Condyloma acuminata caused by human papilloma viruses, (HPV) is a
      sexually transmitted disease (STD) appearing most frequently as soft, pink
      cauliflower like growths in moist areas, such as the genitalia, mouth and other
      places. The disease is highly contagious, can appear singly or in groups, small
      or large. In children, the isolation of a sexually transmitted organism may be
      the first indication that an abuse has occurred. Although the presence of a
      sexually transmissible agent from a child beyond the neonatal period is
      suggestive of sexual abuse, exceptions do exist. CASE PRESENTATION: The authors
      report the clinical case of a five-year-old Caucasian male with lesions located
      in the dorsal surfaces of the posterior tongue and palate. Both lesions had a
      firm consistency, reddish appearance and presence of whitish areas and regions of
      ulceration. During the interview, the mother reported that the boy had been
      sexually abused. CONCLUSION: Sexually transmitted disease may occur during sexual
      abuse. Dentists as well as pediatricians have a role to play in identifying and
      treating these children. The diagnosis is essentially clinical (anamnesis and
      physical examination), but also the use of cytology eventually resorts to biopsy
      of the suspicious lesions for histological examination. The therapeutic option
      was the excision of the lesions.

PMID- 25053205
TI  - The teaching role of residents: Time to come out of the closet?

PMID- 25053206
TI  - The ethics of refusing medical treatment.

PMID- 25053207
TI  - Presence of relaxin-2, oxytocin and their receptors in uterosacral ligaments of
      pre-menopausal patients with and without pelvic organ prolapse.
AB  - OBJECTIVE: Pelvic organ prolapse (POP) is a major health concern for women. Its
      pathophysiology is yet not fully understood. We reported an impaired functional
      state of the smooth muscle compartment in uterosacral ligaments from patients
      with POP, which was cholinergic, stimulated by oxytocin and modulated by relaxin
      2. The current study investigated the presence of oxytocin and relaxin-2 and
      their receptors in the uterosacral ligament from POP/non-POP patients. DESIGN:
      Translational investigation on clinical samples. SETTING: University hospital
      departments. POPULATION AND SAMPLES: Fourty-three samples of uterosacral ligament
      from pre-menopausal patients with (n = 20) and without POP (n = 23). METHODS:
      Presence of relaxin-2, its receptors RXFP1 and RXFP2, and of oxytocin and its
      receptor were analysed by immunohistochemistry and classified using a staining
      score. Additionally, Western blot analysis was performed. MAIN OUTCOME MEASURES:
      Presence patterns with respect to POP and non-POP uterosacral ligament samples
      for pathophysiological understanding of POP. RESULTS: Relaxin-2, oxytocin and
      their receptors were expressed in endothelial cells, the smooth muscle
      compartment and vasa vasorum in the arteries and veins of the uterosacral
      ligament, in the smooth muscle compartment present in the ground reticulum and in
      nerves running through the uterosacral ligament. The presence level of relaxin-2
      was higher in the uterosacral ligament of the POP cohort (p < 0.001).
      CONCLUSIONS: We demonstrated that relaxin-2 had an increased presence in
      uterosacral ligaments from patients with POP, suggesting a role of the relaxin
      system in the pathogenesis of POP and identifying the relaxin system as a
      potential therapeutic target for the pharmacological treatment of POP.

PMID- 25053209
TI  - The aging anesthesiologist: are we asking the right question?

PMID- 25053208
TI  - Time series modelling and forecasting of emergency department overcrowding.
AB  - Efficient management of patient flow (demand) in emergency departments (EDs) has
      become an urgent issue for many hospital administrations. Today, more and more
      attention is being paid to hospital management systems to optimally manage
      patient flow and to improve management strategies, efficiency and safety in such
      establishments. To this end, EDs require significant human and material
      resources, but unfortunately these are limited. Within such a framework, the
      ability to accurately forecast demand in emergency departments has considerable
      implications for hospitals to improve resource allocation and strategic planning.
      The aim of this study was to develop models for forecasting daily attendances at
      the hospital emergency department in Lille, France. The study demonstrates how
      time-series analysis can be used to forecast, at least in the short term, demand
      for emergency services in a hospital emergency department. The forecasts were
      based on daily patient attendances at the paediatric emergency department in
      Lille regional hospital centre, France, from January 2012 to December 2012. An
      autoregressive integrated moving average (ARIMA) method was applied separately to
      each of the two GEMSA categories and total patient attendances. Time-series
      analysis was shown to provide a useful, readily available tool for forecasting
      emergency department demand. 

PMID- 25053210
TI  - Effect of beam steering on the visibility of echogenic and non-echogenic needles:
      a laboratory study.
AB  - PURPOSE: During peripheral nerve block procedures, needle visibility decreases as
      the angle of needle insertion relative to skin increases due to loss of
      reflective signals. The primary aim of our study was to compare the effect of
      beam steering on the visibility of echogenic and non-echogenic block needles.
      METHODS: PAJUNK non-echogenic and echogenic needles were inserted into pork meat
      at 20 degrees , 40 degrees , 60 degrees , and 70 degrees  angles, and electronic
      beam steering was applied at three different angles (shallow, medium, and steep)
      to obtain the best possible needle images. Eleven anesthesiologists blinded to
      the type of needle or use of beam steering scored the images obtained (0 = needle
      not visible; 10 = excellent needle shaft and tip visibility). Mean scores were
      used to classify the needles as poor visibility (mean score 0-3.3), intermediate
      visibility (mean score 3.4-6.6), or good visibility (mean score 6.7-10). RESULTS:
      At 20 degrees , the visibility scores were intermediate to good in all groups. At
      40 degrees , the mean (SD) visibility score for the non-echogenic needle improved
      significantly from 3.1 (1.4) to 7.9 (1.8) with application of beam steering
      (difference = 4.8; 95% confidence interval [CI]: 3.1 to 6.6; P < 0.001). At 60
      degrees , the mean (SD) visibility score for the non-echogenic needle was poor
      0.6 (0.7) and remained poor 2.4 (1.1) with beam steering. One the other hand, the
      echogenic needle without beam steering 6.5 (1.8) scored significantly better than
      the non-echogenic needle with beam steering 2.4 (1.1) (difference = 4.2; 95% CI:
      2.7 to 5.6; P < 0.001). At 70 degrees , the mean needle visibility score was poor
      for the non-echogenic needle with or without beam steering. In contrast, the
      echogenic needle attained an intermediate visibility score with or without beam
      steering. Beam steering did not significantly change the visibility scores of
      either the echogenic or the non-echogenic needle (P = 0.088 and 0.056,
      respectively) at a 70 degrees  angle. CONCLUSION: The PAJUNK echogenic needle,
      with or without beam steering, was more visible when compared with the non
      echogenic needle at 60 degrees  and 70 degrees  angles of insertion. In contrast,
      at a 40 degrees  angle of needle insertion, the non-echogenic needle with beam
      steering was more visible compared with the echogenic needle.

PMID- 25053211
TI  - Order-to-disorder structural transformation of a coordination polymer and its
      influence on proton conduction.
AB  - We observed an ordered-to-disordered structural transformation in a Cu(2+)
      coordination polymer and investigated its influence on the proton conductivity.
      The transformation generated highly mobile proton carriers in the structure. The
      resulting material exhibited a conductivity greater than 10(-2) S cm(-1) at 130 
      degrees C. The structural transformation and the conduction mechanism were
      investigated by EXAFS, TPD-MS and NMR. 

PMID- 25053212
TI  - Atrial fibrillation increases sympathetic and parasympathetic neurons in the
      intrinsic cardiac nervous system.
AB  - BACKGROUND: Chronic atrial fibrillation (AF) leads to heterogeneous autonomic
      nerve innervation termed neural remodeling. The quantitative changes in neural
      density as a function of autonomic remodeling and its association with sustained
      AF has not been previously determined. METHOD AND RESULTS: Seven dogs (paced
      group) were chronically paced with electrodes sutured to the epicardium of left
      atrial appendages. Seven dogs (control animals) were not paced. All paced dogs
      developed sustained AF by 5 weeks of pacing. The fat pads on the atrial
      epicardium containing ganglionated plexuses (GP) were separated along with
      underlying myocardial tissue. Immunocytochemical techniques were used to identify
      the neurons immunoreactive to anti-tyrosine hydroxylase (TH) and anti
      acetylcholine antibodies. After chronic AF, sympathetic and parasympathetic
      neurons in the atrial intrinsic cardiac ganglia increased significantly. In paced
      dogs, the density of sympathetic neurons was 3,022 +/- 507 MUm(2) /mm(2) in the
      right atrial GP (vs control P < 0.01), 8,571 +/- 476 MUm(2) /mm(2) in the ventral
      left atrial GP (vs control P < 0.0001), 6,422 +/- 464 MUm(2) /mm(2) in the dorsal
      atrial GP (vs control P < 0.0001) and 5,392 +/- 595 MUm(2) /mm(2) in the inferior
      vena cava-inferior atrial GP (vs control P <0.0001), respectively. The density of
      parasympathetic neurons was 4,396 +/- 877 MUm(2) /mm(2) in the right atrial GP,
      7,769 +/- 465 MUm(2) /mm(2) in the ventral left atrial GP, 7,016.47 +/- 687
      MUm(2) /mm(2) in the dorsal atrial GP and 5,485 +/- 554 MUm(2) /mm(2) in the
      inferior vena cava-inferior atrial GP, respectively, which was higher than
      control cohorts in corresponding GP (P < 0.05). CONCLUSIONS: This study provides
      evidence for the remodeling in atrial intrinsic cardiac ganglia in the dogs with
      pacing induced AF. A significant increase of sympathetic and parasympathetic
      neurons was present in atrial intrinsic cardiac ganglia.

PMID- 25053213
TI  - Evaluating the effectiveness of health belief model interventions in improving
      adherence: a systematic review.
AB  - Lack of adherence to health-promoting advice challenges the successful prevention
      and management of many conditions. The Health Belief Model (HBM) was developed in
      1966 to predict health-promoting behaviour and has been used in patients with
      wide variety of disease. The HBM has also been used to inform the development of
      interventions to improve health behaviours. Several reviews have documented the
      HBM's performance in predicting behaviour, but no review has addressed its
      utility in the design of interventions or the efficacy of these interventions. A
      systematic review was conducted to identify interventional studies which use the
      HBM as the theoretical basis for intervention design. The HBM has been used
      continuously in the development of behaviour change interventions for 40 years.
      Of 18 eligible studies, 14 (78%) reported significant improvements in adherence,
      with 7 (39%) showing moderate to large effects. However, only six studies used
      the HBM in its entirety and five different studies measured health beliefs as
      outcomes. Intervention success appeared to be unrelated to HBM construct
      addressed challenging the utility of this model as the theoretical basis for
      adherence-enhancing interventions. Interventions need to be described in full to
      allow for the identification of effective components and replication of studies. 

PMID- 25053214
TI  - How can self-efficacy be increased? Meta-analysis of dietary interventions.
AB  - Targeting individuals' beliefs that they are able to eat healthily can improve
      dietary-related behaviours. However, the most effective behaviour change
      techniques (BCTs) to promote dietary self-efficacy have not been systematically
      reviewed. This research addressed this gap. Studies testing the effect of
      interventions on healthy eating and underlying dietary-related self-efficacy,
      within randomised controlled trials, were systematically reviewed in MEDLINE,
      EMBASE and PSYCINFO. Two reviewers independently coded intervention content in
      both intervention and comparison groups. Data pertaining to study quality were
      also extracted. Random effects meta-analysis was used to calculate an overall
      effect size on dietary self-efficacy for each study. The associations between 26
      BCTs and self-efficacy effects were calculated using meta-regression. In some of
      the analyses, interventions that incorporated self-monitoring (tracking one's own
      food-related behaviour), provided feedback on performance, prompted review of
      behavioural goals, provided contingent rewards (rewarding diet success), or
      planned for social support/social change increased dietary self-efficacy
      significantly more than interventions that did not. Stress management was
      consistently associated with self-efficacy effects across all analyses. There was
      strong evidence for stress management and weaker evidence for a number of other
      BCTs. The findings can be used to develop more effective, theory- and evidence
      based behavioural interventions. 

PMID- 25053215
TI  - Carrots, sticks and health behaviours: a framework for documenting the complexity
      of financial incentive interventions to change health behaviours.
AB  - Financial incentive interventions are increasingly used as a method of
      encouraging healthy behaviours, from attending for vaccinations to taking part in
      regular physical activity. There is a growing body of research on the
      effectiveness of financial incentive interventions for health behaviours. Wide
      variations in the nature of these interventions make it difficult to draw firm
      conclusions about what makes an effective incentive, for whom and under what
      circumstances. Whilst there has been some recognition of the theoretical
      complexity of financial incentive interventions for health behaviours, there is
      no framework that categorises these interventions. This limits the research
      community's ability to clearly establish which components of financial incentives
      interventions are more and less effective, and how these components might
      interact to enable behavioural change. We propose a framework for describing
      health-promoting financial incentive interventions. Drawing on our experience of
      a recently completed systematic review, we identify nine domains that are
      required to describe any financial incentive intervention designed to help
      individuals change their health behaviours. These are: direction, form,
      magnitude, certainty, target, frequency, immediacy, schedule and recipient. Our
      framework should help researchers and policy-makers identify the most effective
      incentive configurations for helping individuals adopt healthy behaviours. 

PMID- 25053216
TI  - Changing deliberative and affective responses to health risk: a meta-analysis.
AB  - Perceptions of risk for health outcomes are integral to many theories of health
      behaviour, and are often targeted in interventions. Evidence suggests that
      affective responses to risk, including worry, are empirically distinguishable
      from commonly used perceived risk measures such as perceived susceptibility. The
      aims of this meta-analysis were to (1) examine if perceived susceptibility and
      worry can be independently influenced, and what manipulation types are most
      effective at changing each construct and (2) examine the efficacy of
      interventions to change worry and perceived susceptibility. Thirty-eight studies
      using 43 separate samples provided 78 independent comparisons that were meta
      analysed using the inverse variance method with random-effects modelling. The
      overall effect size (d) was 0.50, 95% CI [0.362, 0.632] for perceived
      susceptibility; and 0.25, 95% CI [0.148, 0.349] for worry. Effect sizes for
      perceived susceptibility were significantly related to those for worry, B=0.495,
      p < 0.001. Moderators of these effects are discussed. The present meta-analysis
      provides further evidence that perceived susceptibility and worry are
      distinguishable but related constructs, and that it is possible to perturb one
      and not the other. 

PMID- 25053218
TI  - Expressive writing interventions in cancer patients: a systematic review.
AB  - Decades of research have suggested that expressive writing produces physical and
      psychological benefits in controlled laboratory experiments among healthy college
      students. This work has been extended to clinical and medical populations,
      including cancer patients. Although expressive writing could be a promising and
      inexpensive intervention for this population, the effects have not been
      systematically examined in oncology samples. A systematic review using PRISMA
      guidelines was conducted for experimental trials of cancer patients who
      participated in an expressive writing intervention. PsycINFO and PubMed/Medline
      were searched for peer-reviewed studies. Thirteen articles met the
      inclusion/exclusion criteria. Although the majority of the intervention effects
      were null, there were several main effects for expressive writing on sleep, pain,
      and general physical and psychological symptoms. Several moderators were
      identified, suggesting that expressive writing may be more or less beneficial
      based on individual characteristics such as social constraints. The reviewed
      studies were limited due to representativeness of the samples, performance,
      detection and patient-reported outcomes biases, and heterogeneity of the
      intervention protocol and writing prompts. Future studies with rigorous designs
      are needed to determine whether expressive writing is therapeutically effective
      in cancer patients. 

PMID- 25053217
TI  - Who are you trying to fool: does weight underreporting by dieters reflect self
      protection or self-presentation?
AB  - Nutritionists are well aware that people tend to underreport their weights, but
      psychologists still often rely on weight self-reports. The present paper reviews
      research on weight underreporting and attempts to identify its underlying
      motivations. Restrained eaters (and overweight individuals) are especially likely
      to underreport their weight. We examine potential reasons for such underreporting
      in these groups, including (1) perceptual biases that make people misperceive
      body weight; (2) an impression-management/self-presentation strategy (telling
      others that one has a more socially desirable weight); or (3) self-protection,
      with underreporting allowing one to protect self-esteem by convincing oneself
      that one is thinner than is really the case. The evidence indicates that
      overweight and restrained women underreport their weight in an attempt to protect
      themselves. The consistent and motivated underreporting of weight by restrained
      eaters not only illuminates their psychological functioning, but indicates a bias
      that may be problematic for research that relies on self-reports. 

PMID- 25053219
TI  - Illness beliefs and self-management in children and young people with chronic
      illness: a systematic review.
AB  - To review the extent to which illness representations, based on Leventhal's
      Common Sense Model, relate to self-management in children and young people with
      chronic physical health conditions. A systematic literature review was carried
      out to identify relevant studies and each included paper was assessed for risk of
      bias. Fifteen papers met criteria for inclusion within the review. The majority
      of studies were cross-sectional, and small sample sizes for some studies made it
      difficult to generalise findings. The method of measuring both illness
      representations and outcomes varied. Timeline, identity, control and consequences
      beliefs were the most frequently assessed domains of illness representations
      included within the studies. While there is variability, there are indications
      that control beliefs, specifically treatment control beliefs, are more
      consistently and strongly associated with self-management than other
      representation domains. Control beliefs should be targeted for intervention in
      studies trying to improve adolescent self-management. In addition, the
      relationship between illness representations and self-management needs to be
      considered within both developmental and systemic contexts. It is likely that the
      variation in self-management will be more fully explained in future research that
      explores the combined effects of individual representations and the influence of
      wider contexts. 

PMID- 25053220
TI  - A single parathyroid hormone level obtained 4 hours after total thyroidectomy
      predicts the need for postoperative calcium supplementation.
AB  - BACKGROUND: Parathyroid hormone (PTH) levels after total thyroidectomy have been
      shown to predict the development of symptomatic hypocalcemia and the need for
      calcium supplementation. This study aimed to determine whether a PTH level drawn
      4 hours postoperatively is as effective as a level drawn on postoperative day 1
      (POD1) in predicting this need. STUDY DESIGN: This is a single-institution
      retrospective review of 4-hour and POD1 PTH levels in patients who underwent
      total thyroidectomy from January 2012 to September 2012. If POD1 PTH was >=10
      pg/mL, patients did not routinely receive supplementation; if PTH was <10 pg/mL,
      patients received oral calcium with or without calcitriol. RESULTS: Of 77
      patients, 20 (26%) had a 4-hour PTH <10 pg/mL; 18 (90%) of these patients had a
      POD1 PTH <10 pg/mL. No patient with a 4-hour PTH >=10 pg/mL had a POD1 PTH <10
      pg/mL. All 18 patients with POD1 PTH <10 pg/mL received calcium supplementation.
      Three additional patients received supplementation due to reported symptoms or
      surgeon preference. A 4-hour PTH >=10 pg/mL compared with a POD1 PTH had a
      similar ability to predict which patients would not need calcium supplementation;
      sensitivity was 98% vs 98%, specificity was 90% vs 86%, and and negative
      predictive value was 95% vs 95%. Of 21 patients who received supplementation, 13
      (62%) also received calcitriol, including 9 patients (69%) with a 4-hour PTH <6
      pg/mL. CONCLUSIONS: A single PTH level obtained 4 hours after total thyroidectomy
      that is >=10 pg/mL accurately identifies patients who do not need calcium
      supplementation or additional monitoring of serum calcium levels. Same-day
      discharge, if deemed safe, can be accomplished with or without calcium
      supplementation based on the 4-hour PTH level. Greater consideration should be
      given to calcitriol supplementation in patients with a 4-hour PTH <6 pg/mL.

PMID- 25053221
TI  - Spontaneous pneumomediastinum: an extensive workup is not required.
AB  - BACKGROUND: Spontaneous pneumomediastinum is a rare entity usually caused by
      alveolar rupture and air tracking along the tracheobronchial tree. Despite its
      benign nature, an extensive workup is often undertaken to exclude hollow viscus
      perforation. We sought to review our experience with this condition and examine
      the optimal management strategy. STUDY DESIGN: We conducted a retrospective
      review of all radiographic pneumomediastinum cases at a tertiary hospital between
      2006 and 2011. The main outcomes measures included length of hospital stay,
      mortality, and need for investigative procedures. RESULTS: Forty-nine patients
      with spontaneous pneumomediastinum were identified, including 26 male patients
      (53%). Mean age was 19 +/- 9 years. Chest pain was the most common presenting
      symptom (65%), followed by dyspnea (51%). Forceful coughing (29%) or vomiting
      (16%) were the most common eliciting factors, and no precipitating event was
      identified in 41% of patients. Computed tomography was performed in 38 patients
      (78%) and showed a pneumomediastinum that was not seen on chest x-ray in 9
      patients. Esophagography was performed in 17 patients (35%) and was invariably
      negative for a leak. Thirty-eight patients (78%) were hospitalized for a mean of
      1.8 +/- 2.6 days. No mortality was recorded. Compared with patients who presented
      with pneumomediastinum secondary to esophageal perforation, spontaneous
      pneumomediastinum patients were younger, had a lower white cell count, and were
      less likely to have a pleural effusion. CONCLUSIONS: Spontaneous
      pneumomediastinum is a benign entity and rarely correlates with true esophageal
      perforation. Additional investigation with esophagography or other invasive
      procedures should be performed selectively with the aim of expediting the
      patient's care. The prognosis is excellent with conservative management and the
      risk for recurrence is low.

PMID- 25053222
TI  - Effect of wound classification on risk adjustment in American College of Surgeons
      NSQIP.
AB  - BACKGROUND: Surgical wound classification has been used in risk-adjustment
      models. However, it can be subjective and could potentially improperly bias
      hospital quality comparisons. The objective is to examine the effect of wound
      classification on hospital performance risk-adjustment models. STUDY DESIGN:
      Retrospective review of the 2011 American College of Surgeons NSQIP database was
      conducted for the following wound classification categories: clean, clean
      contaminated, contaminated, and dirty-infected. To assess the influence of wound
      classification on risk adjustment, 2 models were developed for all outcomes: 1
      including and 1 excluding wound classification. For each model, hospital
      postoperative complications were estimated using hierarchical multivariable
      regression methods. Absolute changes in hospital rank, correlations of odds
      ratios, and outlier status agreement between models were examined. RESULTS: Of
      the 442,149 cases performed in 315 hospitals: 53.6% were classified as clean;
      34.2% as clean-contaminated; 6.7% as contaminated; and 5.5% as dirty-infected.
      The surgical site infection rate was highest in dirty-infected (8.5%) and lowest
      in clean (1.8%) cases. For overall surgical site infection, the absolute change
      in risk-adjusted hospital performance rank between models, including vs excluding
      wound classification, was minimal (mean 4.5 of 315 positions). The correlations
      between odds ratios of the 2 performance models were nearly perfect (R = 0.9976,
      p < 0.0001), and outlier status agreement was excellent (kappa = 0.95ss08, p <
      0.0001). Similar findings were observed in models of subgroups of surgical site
      infections and other postoperative outcomes. CONCLUSIONS: In circumstances where
      alternate information is available for risk adjustment, there appear to be
      minimal differences in performance models that include vs exclude wound
      classification. Therefore, the American College of Surgeons NSQIP is critically
      evaluating the continued use of wound classification in hospital performance risk
      adjustment models.

PMID- 25053223
TI  - A micro RNA-146a polymorphism is associated with coronary restenosis.
AB  - The association of the miRNA-146a polymorphism rs2910164 with atherosclerosis and
      restenosis was investigated. We found no association with atherosclerosis;
      however, we found a negative association for the G/C (P = 0.007) and a positive
      association for the C/C genotype with the risk of restenosis, which is the main
      drawback for cardiac surgery. 

PMID- 25053224
TI  - Multimodal sensory feedback associated with motor attempts alters BOLD responses
      to paralyzed hand movement in chronic stroke patients.
AB  - Electroencephalogram-based brain-computer interfaces (BCI) have been used as a
      potential tool for training volitional regulation of corticomuscular drive in
      patients who have severe hemiplegia due to stroke. However, it is unclear whether
      ERD observed while attempting motor execution can be regarded as a neural marker
      that represents M1 excitability in survivors of severe stroke. Therefore we
      investigated the association between ERD and the blood-oxygen-level-dependent
      (BOLD) fMRI signal during attempted movement of a paralyzed finger in stroke
      patients. Nine chronic stroke patients received BCI training for finger extension
      movement 1 h daily for a duration of 1 month. The sensorimotor rhythm was
      recorded from the sensorimotor area of the damaged hemisphere, and ongoing
      amplitude variations were monitored using a BCI system. Either a visual alert or
      the action of a motor-driven orthosis was triggered in response to ERD of the
      sensorimotor rhythm while patients attempted extension movements of the paralyzed
      fingers. Inter-subject covariance between ERD and the BOLD response in the
      sensorimotor areas was calculated. After BCI training, an increased ERD over the
      damaged hemisphere was confirmed in all participants while they attempted
      extension of the affected finger and this increase was associated with a BOLD
      response in primary sensorimotor area. Whole-brain MRI revealed that the primary
      sensorimotor area and supplementary motor area were activated in the damaged
      hemisphere after 1 month of BCI training. ERD reflects the BOLD responses of the
      primary motor areas in either hemisphere while patients who have severe chronic
      hemiplegia due to a stroke attempt an extension movement of the paralyzed
      fingers. One month of BCI can alter motor-related brain area activation.
      Combining BCI with other methods to facilitate such changes may help to implement
      BCI for motor rehabilitation after stroke. 

PMID- 25053225
TI  - Applying the Chicago Classification criteria of esophageal motility to a
      pediatric cohort: effects of patient age and size.
AB  - BACKGROUND: Applying the 2012 Chicago Classification (CC) of esophageal motility
      disorders to pediatric patients is problematic as it relies upon adult-derived
      criteria. As shorter esophageal length and smaller esophago-gastric junction
      (EGJ) diameter may influence CC metrics, we explored the potential for age- and
      size-adjustment of diagnostic criteria. METHODS: We evaluated 76 high-resolution
      solid state impedance-manometry recordings in children referred for manometry
      (32M; mean age 9 +/- 1 years) and 25 recordings from healthy adult subjects (7M;
      mean age 36 +/- 2 years). CC metrics; integrated relaxation pressure (IRP4s,
      mmHg), contractile front velocity (CFV, cm/s), distal contractile integral (DCI,
      mmHg cm/s), distal latency (DL, s), and peristaltic break size (BS, cm) were
      derived for 10 liquid swallows using CC analysis software. Effects of age and
      size were examined using regression analysis. KEY RESULTS: Younger patient age
      and shorter size correlated significantly with greater IRP4s (p < 0.05), shorter
      DL (p < 0.001) and smaller BS (p < 0.05). Standard diagnostic CC criteria were
      adjusted using the slope of the linear regression equation to define the age/size
      related trend. Sixty-six percent of the pediatric cohort showed abnormal motility
      when applying standard CC criteria. Adjustment for age and size reduced this to
      50% and 53% respectively, with the largest reduction being in the IRP4s- and DL
      dependent disorders EGJ outflow obstruction and diffuse esophageal spasm (13% to
      7% and 5% and 14% to 1 and 5%, respectively). CONCLUSIONS & INFERENCES: CC
      metrics, particularly IRP4s and DL, are age and size dependent, and therefore,
      require adjustment to improve accuracy of diagnosis of esophageal motility
      disorders in children.

PMID- 25053226
TI  - Freshwater movement patterns by juvenile Pacific salmon Oncorhynchus spp. before
      they migrate to the ocean: Oh the places you'll go!
AB  - Juvenile movement patterns for coho salmon Oncorhynchus kisutch and Chinook
      salmon Oncorhynchus tshawytscha from two large interior rivers of British
      Columbia, Canada, were examined. Otoliths from post-spawned fishes were collected
      on spawning grounds and elemental signatures were determined through transects
      from sectioned otoliths using laser ablation-inductively coupled plasma-mass
      spectrometry (LA-ICP-MS). Large variations in otolith elemental signatures were
      found during the freshwater life stage indicative of movement downstream to
      rivers and tributaries that differed in elemental signature. This study
      highlights that downstream movements occur before migration to the ocean during
      the parr-smolt transformation. Extensive downstream movements of parr appear to
      be a successful life-history strategy based on variations observed in the otolith
      elemental signatures of spawners. Movements downstream in parr and the remarkable
      homing ability of adults also suggest that imprinting to natal streams must occur
      prior to the parr-smolt transformation.

PMID- 25053227
TI  - Molecular mechanisms associated with PTHrP-induced proliferation of colon cancer
      cells.
AB  - Parathyroid Hormone-related Protein (PTHrP) is normally produced in many tissues
      and is recognized for its endocrine, paracrine, autocrine and intracrine modes of
      action. PTHrP is also implicated in different types of cancer and its expression
      correlates with the severity of colon carcinoma. Using the human colon cell line
      Caco-2 we recently obtained evidence that PTHrP, through a paracrine pathway,
      exerts a protective effect under apoptotic conditions. However, if exogenous
      PTHrP is able or not to induce the proliferation of these intestinal tumor cells
      is not known. We found that PTHrP treatment increases the number of live Caco-2
      cells. The hormone induces the phosphorylation and nuclear translocation of ERK
      1/2, alpha p38 MAPK, and Akt, without affecting JNK phosphorylation. In addition,
      PTHrP-dependent ERK phosphorylation is reverted when PI3K activity was inhibited.
      Following MAPKs nuclear translocation, the transcription factors ATF-1 and CREB
      were activated in a biphasic manner. In addition PTHrP induces the translocation
      into the nucleus of beta-catenin, protein that plays key role in maintaining the
      growth and proliferation of colorectal cancer, and increases the amount of both
      positive cell cycle regulators c-Myc and Cyclin D. Studies with ERK1/2, alpha p38
      MAPK, and PI3K specific inhibitors showed that PTHrP regulates Caco-2 cell
      proliferation via these signaling pathways. In conclusion, the results obtained
      in this work expand our knowledge on the role of exogenous PTHrP in intestinal
      tumor cells and identify the signaling pathways that are involved in the
      mitogenic effect of the hormone on Caco-2 cells.

PMID- 25053228
TI  - Factors affecting response to biologic treatment in psoriasis.
AB  - Psoriasis is a chronic, immune-mediated inflammatory skin disease, affecting
      approximately 2-4% of the population in western countries. Patients with a more
      severe form of the disease are typically considered for systemic therapy,
      including biologics. In spite of the overall superiority of biologic agents, the
      treatment response may differ substantially among individual patients. As with
      other medical conditions, a range of factors contribute to response heterogeneity
      observed in psoriasis. Proper identification of these factors can significantly
      improve the therapeutic decisions. This review focuses on potential genetic and
      nongenetic factors that may affect the treatment response and outcomes in
      patients with psoriasis.

PMID- 25053229
TI  - Biodistribution and PET imaging of a novel [68Ga]-anti-CD163-antibody conjugate
      in rats with collagen-induced arthritis and in controls.
AB  - PURPOSE: The hemoglobin scavenger receptor CD163 is exclusively expressed on
      monocytes and tissue macrophages, also at sites of inflammation. We examined
      whether gallium-68 (Ga-68)-labeled anti-CD163-antibody can detect the receptor in
      vivo. PROCEDURES: We radiolabeled anti-CD163 antibody with Ga-68 and evaluated
      stability and binding specificity of the conjugate ([(68)Ga]ED2) in vitro.
      Furthermore, tracer biodistribution was assessed in vivo in healthy rats and rats
      with acute collagen-induced arthritis (CIA) by MicroPET and tissue analysis.
      RESULTS: Radiosynthesis of [(68)Ga]ED2 antibody yielded a tracer with high
      specific activity and radiochemical purity. [(68)Ga]ED2 bound specifically to
      CD163 in vitro. In rats, [(68)Ga]ED2 rapidly accumulated in macrophage-rich
      tissues. The arthritic paws exhibited a low but significant [(68)Ga]ED2 uptake.
      Interestingly, the systemic distribution was also changed in the sense that a
      significantly higher liver uptake and lower spleen uptake of [(68)Ga]ED2 was
      measured in CIA rats that accordingly showed a corresponding change in level of
      CD163 expression. CONCLUSIONS: [(68)Ga]ED2 specifically binds CD163 in vitro and
      in vivo. Biodistribution studies in CIA rats suggest that this novel tool may
      have applications in studies of inflammatory diseases.

PMID- 25053230
TI  - Fungal polyketide biosynthesis - a personal perspective.
AB  - This Viewpoint article provides a personal viewpoint of research in the area of
      fungal polyketide biosynthesis. It spans the period from the first applications
      and subsequent development of modern stable-isotope labelling methods, the
      isolation, sequencing and expression of PKS genes, biochemical and structural
      characterisation of PKS domains, fungal genome sequencing, through to genetic
      engineering of whole pathways. This article forms part of a "trilogy" of related
      Viewpoints from three close contemporaries who have been privileged to share in
      these developments since their outset over forty years ago and to enjoy both
      professional and personal interactions throughout that time. 

PMID- 25053231
TI  - Total pancreatectomy with islet cell auto-transplantation: update and outcomes
      from major centers.
AB  - OPINION STATEMENT: Chronic pancreatitis is the result of irreversible damage to
      pancreatic acinar cells, and can result in debilitating chronic pain for
      patients. Treatment centers on pain relief, often with chronic narcotic use.
      Surgical therapy consists of both resection procedures to remove affected
      pancreatic parenchyma and drainage procedures to facilitate drainage of the main
      pancreatic duct. Total pancreatectomy historically was utilized in extreme cases
      due to the brittle glucose control that followed from the total loss of islet
      cells. Total pancreatectomy with islet cell auto-transplantation (TP-AIT) is
      gaining in popularity due to the maintenance of beta cell mass and the ability of
      patients to potentially be insulin independent post-operatively. TP-AIT is very
      helpful in the treatment of pain for patients with chronic pancreatitis. The
      overall majority of patients have an improvement in pain and quality-of-life
      scores. AIT also allows the majority of patients to have minimal insulin
      requirements post-operatively. With proper patient selection, these outcomes can
      be achieved.

PMID- 25053232
TI  - Experimental proof of concept of nanoparticle-assisted STED.
AB  - We imaged core-shell nanoparticles, consisting of a dye-doped silica core covered
      with a layer of gold, with a stimulated emission depletion, fluorescence lifetime
      imaging (STED-FLIM) microscope. Because of the field enhancement provided by the
      localized surface plasmon resonance of the gold shell, we demonstrate a reduction
      of the STED depletion power required to obtain resolution improvement by a factor
      of 4. This validates the concept of nanoparticle-assisted STED (NP-STED), where
      hybrid dye-plasmonic nanoparticles are used as labels for STED in order to
      decrease the depletion powers required for subwavelength imaging. 

PMID- 25053233
TI  - Mediastinal Burkitt lymphoma in childhood.

PMID- 25053234
TI  - B-type natriuretic peptides for the prediction of cardiovascular events in
      patients with stable coronary heart disease: the Heart and Soul Study.
AB  - BACKGROUND: Brain-type natriuretic peptide (BNP) and the amino-terminal fragment
      of its prohormone (NT-proBNP) are known predictors of cardiovascular outcomes in
      patients with coronary heart disease; however, the relative prognostic value of
      these 2 biomarkers for secondary events remains unclear. METHODS AND RESULTS: In
      983 participants with stable coronary heart disease, we evaluated the association
      of BNP and NT-proBNP with time to hospitalization for heart failure, nonfatal
      myocardial infarction, stroke or transient ischemic attack, cardiovascular death,
      and combined major adverse cardiovascular events (MACE). During an average follow
      up of 6.5+/-3.3 years, both BNP and NT-proBNP were associated with increased risk
      of MACE in a multivariable-adjusted model (hazard ratio per standard deviation of
      log BNP: 1.58; 95% CI: 1.32 to 1.89; hazard ratio per standard deviation of log
      NT-proBNP: 1.84; 95% CI: 1.52 to 2.24). When added to traditional risk factors,
      NT-proBNP predicted MACE better than BNP (C statistic: 0.76 versus 0.72,
      P<0.001). Similarly, the addition of NT-proBNP resulted in a greater net
      reclassification improvement for predicting MACE than the addition of BNP (65%
      for NT-proBNP, 56% for BNP). CONCLUSIONS: Both BNP and NT-proBNP were significant
      predictors of MACE in stable coronary heart disease; however, NT-proBNP was
      superior to BNP for net risk reclassification for MACE.

PMID- 25053235
TI  - Hope for disease-modifying treatment of systemic sclerosis/scleroderma.

PMID- 25053237
TI  - Fatty liver creates a pro-metastatic microenvironment for hepatocellular
      carcinoma through activation of hepatic stellate cells.
AB  - Fatty liver (FL) is associated with development of hepatocellular carcinoma
      (HCC). However, whether FL itself promotes the progression of HCC is unclear. We
      recently found that hepatic stellate cells (HSCs) were prominently activated in
      the steatotic liver. Here, we investigated whether steatotic livers promote HCC
      progression and whether HSCs of steatotic liver are associated with HCC
      progression. We implanted rat HCC cells into diet-induced steatotic livers in
      rats via portal vein injection. Thereafter, HSCs and HCC cells were co-implanted
      subcutaneously into nude rats. Migration and proliferation of HCC cells were
      measured, and activation of ERK and Akt in these cells was determined by western
      blotting. Chemokines secreted from HSCs and HCC cells were also evaluated by
      ELISA. Steatotic livers significantly promoted HCC metastasis compared with non
      steatotic livers. Additionally, co-implantation of HCC cells with HSCs from
      steatotic livers produced significantly larger tumors in recipient rats as
      compared to those induced by HCC cells co-implanted with HSCs from normal livers
      (NLs). HSCs isolated from steatotic livers, compared with HSCs isolated from NLs,
      secreted greater amounts of interleukin-1alpha, vascular endothelial growth
      factor, and transforming growth factor-beta. These cytokines may enhance the
      proliferation and migration of HCC cells by increasing the phosphorylation of ERK
      and Akt in HCC cells. Moreover, we noted that the Rho-kinase inhibitor
      deactivated activated HSCs and attenuated HCC progression. In conclusion, the rat
      steatotic liver microenvironment favors HCC metastasis, and this effect appears
      to be promoted by activated HSCs in the steatotic liver. 

PMID- 25053238
TI  - Healable supramolecular polymers as organic metals.
AB  - Organic materials exhibiting metallic behavior are promising for numerous
      applications ranging from printed nanocircuits to large area electronics.
      However, the optimization of electronic conduction in organic metals such as
      charge-transfer salts or doped conjugated polymers requires high crystallinity,
      which is detrimental to their processability. To overcome this problem, the
      combination of the electronic properties of metal-like materials with the
      mechanical properties of soft self-assembled systems is attractive but
      necessitates the absence of structural defects in a regular lattice. Here we
      describe a one-dimensional supramolecular polymer in which photoinduced through
      space charge-transfer complexes lead to highly coherent domains with delocalized
      electronic states displaying metallic behavior. We also reveal that diffusion of
      supramolecular polarons in the nanowires repairs structural defects thereby
      improving their conduction. The ability to access metallic properties from
      mendable self-assemblies extends the current understanding of both fields and
      opens a wide range of processing techniques for applications in organic
      electronics. 

PMID- 25053236
TI  - Pharmacokinetics and toxicology of a fibroblast activation protein (FAP)
      activated prodrug in murine xenograft models of human cancer.
AB  - BACKGROUND: As carcinoma progresses, the stroma undergoes a variety of phenotypic
      changes, including the presence of carcinoma-associated fibroblasts (CAFs) that
      express fibroblast activation protein (FAP). FAP is a post-prolyl endopeptidase
      whose expression in a healthy adult is largely restricted to the cancer
      associated stroma. FAP-targeted prodrugs with a 100-fold greater therapeutic
      window over the parent compound were previously generated. METHODS: Prodrugs and
      non-cleavable controls were incubated in the presence of FAP. Plasma and tumor
      half-lives (t1/2) of the full-length and active forms of the prodrugs were
      determined using LCMS. Biodistribution studies of prodrug activation were
      performed. Histopathological analysis of tissues from treated animals were
      compared to vehicle-treated controls. Toxicity and efficacy studies were
      performed in human breast (MDA-MB-231 and MCF-7) and prostate (LNCaP) cancer
      xenografts models. RESULTS: These FAP-activated prodrugs have a significantly
      slower clearance from tumor tissue than the circulation (~12 vs. ~4.5 hr).
      Micromolar concentrations of active drug persist in the tumor. Active drug is
      detected in non-target tissues; however, histopathologic evaluation reveals no
      evidence of drug-induced toxicity. A FAP-activated prodrug (ERGETGP-S12ADT)
      inhibits tumor growth in multiple human breast and prostate cancer xenograft
      models. The anti-tumor effect is comparable to that observed with docetaxel, but
      results in significantly less toxicity. CONCLUSION: FAP-activated prodrugs are a
      viable strategy for the management of prostate and other cancers. These prodrugs
      exhibit less toxicity than a commonly used chemotherapeutic agent. Further
      refinement of the FAP cleavage site for greater specificity may reduce prodrug
      activation in non-target tissues and enhance clinical benefit.

PMID- 25053239
TI  - AncesTrees: ancestry estimation with randomized decision trees.
AB  - In forensic anthropology, ancestry estimation is essential in establishing the
      individual biological profile. The aim of this study is to present a new program-
      AncesTrees--developed for assessing ancestry based on metric analysis. AncesTrees
      relies on a machine learning ensemble algorithm, random forest, to classify the
      human skull. In the ensemble learning paradigm, several models are generated and
      co-jointly used to arrive at the final decision. The random forest algorithm
      creates ensembles of decision trees classifiers, a non-linear and non-parametric
      classification technique. The database used in AncesTrees is composed by 23
      craniometric variables from 1,734 individuals, representative of six major
      ancestral groups and selected from the Howells' craniometric series. The program
      was tested in 128 adult crania from the following collections: the African
      slaves' skeletal collection of Valle da Gafaria; the Medical School Skull
      Collection and the Identified Skeletal Collection of 21st Century, both curated
      at the University of Coimbra. The first step of the test analysis was to perform
      ancestry estimation including all the ancestral groups of the database. The
      second stage of our test analysis was to conduct ancestry estimation including
      only the European and the African ancestral groups. In the first test analysis,
      75% of the individuals of African ancestry and 79.2% of the individuals of
      European ancestry were correctly identified. The model involving only African and
      European ancestral groups had a better performance: 93.8% of all individuals were
      correctly classified. The obtained results show that AncesTrees can be a valuable
      tool in forensic anthropology.

PMID- 25053240
TI  - Highlights in clinical autonomic neurosciences: novel insights about vasovagal
      syncope and postural tachycardia syndrome from autonomic testing.

PMID- 25053241
TI  - Spontaneous unilateral renal dysplasia in a clinically healthy cynomolgus monkey
      (Macaca fascicularis).
AB  - Renal dysplasia is a congenital renal malformation characterized by disruption of
      normal renal development with asynchronous differentiation of nephrons,
      collecting ducts, and parenchyma and abnormal patterning of cortical and
      medullary tissues. The present article describes unilateral renal dysplasia
      discovered in a cynomolgus monkey from a routine toxicology study. The affected
      kidney was small and characterized by extensive interstitial fibrosis with the
      formation of fibromuscular collars around glomeruli and tubules, immature
      nephrons, and persistent mesenchyme encompassing few collecting ducts. The
      present case is remarkable in that there is a paucity of reports describing
      histopathologic findings of spontaneously occurring renal dysplasia in
      preclinical test species for use in large animal toxicity studies. 

PMID- 25053242
TI  - Anesthetic drugs in congenital heart disease.
AB  - The structural defects associated with the various forms of congenital heart
      disease lead to pathological and functional changes that place patients at risk
      for adverse events, and in fact the perioperative incidence of morbidity and
      mortality has been documented to be increased in children with congenital heart
      disease. Patients with congenital heart disease can present to the
      anesthesiologist in a relatively precarious state of balance of several
      hemodynamic factors, including preload, ventricular contractility, systemic
      vascular resistance, pulmonary vascular resistance, heart rate, and cardiac
      rhythm. Anesthetic drugs can affect each of these, and an ideal anesthetic drug
      for such patients does not exist. The purpose of this article is to review the
      hemodynamic effects of anesthetic drugs and how they may contribute to the
      occurrence of adverse events in children with congenital heart disease. 

PMID- 25053243
TI  - Unilateral breast metastasis from alveolar rhabdomyosarcoma in adult detected by
      18F-FDG PET/CT.

PMID- 25053244
TI  - Donor acute kidney injury and short-term graft outcome in renal transplantation.
AB  - BACKGROUND: With increased waiting times for kidney transplantation, marginal
      organs from expanded criteria donors (ECD) are increasingly offered for
      allocation. In addition to ECD status, donors may have suffered from acute kidney
      injury (AKI) prior to organ procurement. METHODS: In this retrospective cohort
      study, we studied short-term allograft function in 517 kidney transplants
      performed between the years 2008-2014. Recipients of allografts from deceased
      organ donors were categorized as standard criteria donors (SCD) or ECD with or
      without AKI defined by RIFLE criteria. RESULTS: Of 382 deceased donations, 174
      (45.5%) were classified as ECD and 63 (16.5%) fulfilled AKI criteria. Donor
      creatinine on hospital admission was similar, whereas creatinine before organ
      procurement differed (p < 0.001). Despite these differences, serum creatinine and
      eGFR at discharge and after one yr showed only minor differences between kidneys
      with or without AKI. In multivariate linear regression analyses, donor AKI was
      not a predictor of one-yr allograft function. CONCLUSIONS: Given the poor
      prognosis of dialysis patients and the increase in waiting time, kidneys from SCD
      and ECD donors with AKI should be allocated for transplantation. In case of ECD
      donors with AKI, recipients should be informed about the possibility of permanent
      non-function or early graft loss.

PMID- 25053245
TI  - MXD3 regulation of DAOY cell proliferation dictated by time course of activation.
AB  - BACKGROUND: MXD3 is a basic-helix-loop-helix-leucine-zipper transcription factor
      involved in cellular proliferation. In previous studies we demonstrated that
      knock-down of MXD3 in the human medulloblastoma cell line DAOY resulted in
      decreased proliferation. Surprisingly, overexpression of MXD3 in DAOY cells also
      decreased proliferation and increased cell death, suggesting that persistent
      expression of MXD3 triggers an apoptotic response, perhaps as a fail-safe
      mechanism. To investigate this apparent paradox in detail we developed a
      tamoxifen inducible system to analyze the temporal effects of MXD3 in the
      proliferation and transcriptional response of DAOY cells upon acute induction
      compared with long-term expression of MXD3. RESULTS: We find that acute induction
      of MXD3 initially promotes cell cycle progression as assessed by a transient
      increase in bromodeoxyuridine incorporation. However, persistent induction of
      MXD3 ultimately results in decreased proliferation based on cell counts. Finally,
      with microarray expression profiling and gene ontology analysis we identify
      several major pathways enriched in response to acute (immune response, apoptosis,
      cell cycle) versus persistent (cell adhesion) MXD3 activation. CONCLUSIONS: In
      this study, we demonstrate that acute MXD3 activation results in a transient
      increase in cell proliferation while persistent activation of MXD3 eventually
      results in an overall decrease in cell number, suggesting that the time course of
      MXD3 expression dictates the cellular outcome. Microarray expression profiling
      and gene ontology analysis indicate that MXD3 regulates distinct genes and
      pathways upon acute induction compared with persistent expression, suggesting
      that the cellular outcome is specified by changes in MXD3 transcriptional program
      in a time-dependent manner.

PMID- 25053246
TI  - [Severe acute liver failure due to herpes simplex virus infection in an
      immunocompetent patient].

PMID- 25053247
TI  - Our paper 20 years later: how has withdrawal from mechanical ventilation changed?
AB  - Withdrawal from mechanical ventilation (or weaning) is one of the most common
      procedures in intensive care units. Almost 20 years ago, we published one of the
      seminal papers on weaning in which we showed that the best method for withdrawal
      from mechanical ventilation in difficult-to-wean patients was a once-daily
      spontaneous breathing trial with a T-piece. Progress has not stood still, and in
      the intervening years up to the present several other studies, by our group and
      others, have shaped weaning into an evidence-based technique. The results of
      these studies have been applied progressively to routine clinical practice.
      Currently, withdrawal from mechanical ventilation can be summarized as the
      evaluation of extubation readiness based on the patient's performance during a
      spontaneous breathing trial. This trial can be performed with a T-piece, which is
      the most common approach, or with continuous positive airway pressure or low
      levels of pressure support. Most patients can be disconnected after passing the
      first spontaneous breathing trial. In patients who fail the first attempt at
      withdrawal, the use of a once-daily spontaneous breathing trial or a gradual
      reduction in pressure support are the preferred weaning methods. However, new
      applications of standard techniques, such as noninvasive positive pressure
      ventilation, or new methods of mechanical ventilation, such as automatic tube
      compensation, automated closed-loop systems, and automated knowledge-based
      weaning systems, can play a role in the management of the patients with difficult
      or prolonged weaning.

PMID- 25053248
TI  - Risk factors for target non-attainment during empirical treatment with beta
      lactam antibiotics in critically ill patients.
AB  - PURPOSE: Risk factors for beta-lactam antibiotic underdosing in critically ill
      patients have not been described in large-scale studies. The objective of this
      study was to describe pharmacokinetic/pharmacodynamic (PK/PD) target non
      attainment envisioning empirical dosing in critically ill patients and
      considering a worst-case scenario as well as to identify patient characteristics
      that are associated with target non-attainment. METHODS: This analysis uses data
      from the DALI study, a prospective, multi-centre pharmacokinetic point-prevalence
      study. For this analysis, we assumed that these were the concentrations that
      would be reached during empirical dosing, and calculated target attainment using
      a hypothetical target minimum inhibitory concentration (MIC), namely the
      susceptibility breakpoint of the least susceptible organism for which that
      antibiotic is commonly used. PK/PD targets were free drug concentration
      maintained above the MIC of the suspected pathogen for at least 50 % and 100 % of
      the dosing interval respectively (50 % and 100 % f T (>MIC)). Multivariable
      analysis was performed to identify factors associated with inadequate antibiotic
      exposure. RESULTS: A total of 343 critically ill patients receiving eight
      different beta-lactam antibiotics were included. The median (interquartile range)
      age was 60 (47-73) years, APACHE II score was 18 (13-24). In the hypothetical
      situation of empirical dosing, antibiotic concentrations remained below the MIC
      during 50 % and 100 % of the dosing interval in 66 (19.2 %) and 142 (41.4 %)
      patients respectively. The use of intermittent infusion was significantly
      associated with increased risk of non-attainment for both targets; creatinine
      clearance was independently associated with not reaching the 100 % f T( >MIC)
      target. CONCLUSIONS: This study found that-in empirical dosing and considering a
      worst--case scenario--19 % and 41 % of the patients would not achieve antibiotic
      concentrations above the MIC during 50 % and 100 % of the dosing interval. The
      use of intermittent infusion (compared to extended and continuous infusion) was
      the main determinant of non-attainment for both targets; increasing creatinine
      clearance was also associated with not attaining concentrations above the MIC for
      the whole dosing interval. In the light of this study from 68 ICUs across ten
      countries, we believe current empiric dosing recommendations for ICU patients are
      inadequate to effectively cover a broad range of susceptible organisms and need
      to be reconsidered.

PMID- 25053249
TI  - Progression of Coxiella burnetii infection after implementing a two-year
      vaccination program in a naturally infected dairy cattle herd.
AB  - BACKGROUND: The high prevalence of Coxiella burnetii infection in dairy cattle
      herds recently reported and the long survival time of the bacterium in the
      environment pose a risk to human and animal health that calls for the
      implementation of control measures at herd level. This study presents the results
      of a 2-year vaccination program with an inactivated phase I vaccine in a Spanish
      dairy herd naturally infected with C. burnetii. Calves older than 3 months and
      non-pregnant heifers and cows were vaccinated in April 2011 and the farm was
      subsequently visited at a monthly basis for vaccination of recently calved cows
      and calves that reached the age of 3 months. Annual booster doses were given to
      previous vaccinated animals as well. The effectiveness of the vaccine was
      assessed in terms of level of C. burnetii shedding through milk and uterine
      fluids and environmental contamination as determined by polymerase chain reaction
      (PCR). RESULTS: The percentage of shedder animals through uterine fluids and milk
      progressively decreased, and C. burnetii DNA load in bulk-tank milk samples was
      low at the end of the study. The average seroconversion rate in not yet
      vaccinated animals, which acted as control group, was 8.6% during the first year
      and 0% in the second year. DNA of C. burnetii was found in aerosols and dust
      samples taken in the calving area only at the beginning of the study, whereas
      slurry samples remained C. burnetii PCR positive for at least 18 months. Multiple
      Locus Variable number tandem-repeat Analysis identified the same genotype in all
      C. burnetii DNA positive samples. CONCLUSIONS: In the absence of any changes in
      biosecurity, the overall reduction of C. burnetii infection in animals to 1.2%
      milk shedders and the reduced environment contamination found at the end of the
      study was ascribed to the effects of vaccination together with the culling of
      milk shedders. Vaccination has to be planned as a medium-long term strategy to
      suppress risks of re-infection.

PMID- 25053250
TI  - Influence of soil and climate heterogeneity on the performance of economic
      instruments for reducing nitrate leaching from agriculture.
AB  - Economic instruments can be used to control groundwater nitrate pollution due to
      the intensive use of fertilizers in agriculture. In order to test their
      efficiency on the reduction of nitrate leaching, we propose an approach based on
      the combined use of production and pollution functions to derive the impacts on
      the expected farmer response of these instruments. Some of the most important
      factors influencing nitrate leaching and crop yield are the type of soil and the
      climatic conditions. Crop yield and nitrate leaching responses to different soil
      and climatic conditions were classified by means of a cluster analysis, and crops
      located in different areas but with similar response were grouped for the
      analysis. We use a spatial economic optimization model to evaluate the potential
      of taxes on nitrogen fertilizers, water prices, and taxes on nitrate emissions to
      reduce nitrate pollution, as well as their economic impact in terms of social
      welfare and farmers' net benefits. The method was applied to the Mancha Oriental
      System (MOS) in Spain, a large area with different soil types and climatic
      conditions. We divided the study area into zones of homogeneous crop production
      and nitrate leaching properties. Results show spatially different responses of
      crop growth and nitrate leaching, proving how the cost-effectiveness of pollution
      control instruments is contingent upon the spatial heterogeneities of the
      problem. 

PMID- 25053251
TI  - Full immersion simulation: validation of a distributed simulation environment for
      technical and non-technical skills training in Urology.
AB  - OBJECTIVE: To evaluate the face, content and construct validity of the
      distributed simulation (DS) environment for technical and non-technical skills
      training in endourology. To evaluate the educational impact of DS for urology
      training. SUBJECTS AND METHODS: DS offers a portable, low-cost simulated
      operating room environment that can be set up in any open space. A prospective
      mixed methods design using established validation methodology was conducted in
      this simulated environment with 10 experienced and 10 trainee urologists. All
      participants performed a simulated prostate resection in the DS environment.
      Outcome measures included surveys to evaluate the DS, as well as comparative
      analyses of experienced and trainee urologist's performance using real-time and
      'blinded' video analysis and validated performance metrics. Non-parametric
      statistical methods were used to compare differences between groups. RESULTS: The
      DS environment demonstrated face, content and construct validity for both non
      technical and technical skills. Kirkpatrick level 1 evidence for the educational
      impact of the DS environment was shown. Further studies are needed to evaluate
      the effect of simulated operating room training on real operating room
      performance. CONCLUSIONS: This study has shown the validity of the DS environment
      for non-technical, as well as technical skills training. DS-based simulation
      appears to be a valuable addition to traditional classroom-based simulation
      training.

PMID- 25053253
TI  - Gender-based differences in the high-risk sexual behaviours of young people aged
      15-29 in Melilla (Spain): a cross-sectional study.
AB  - BACKGROUND: Research confirms the existence of gender-based differences regarding
      the high-risk sexual behaviour (non-use of condoms and casual partners) of young
      men and women. The objectives were to provide evidence for this association; to
      analyse the reasons why both sexes have sexual relations with casual partners and
      to ascertain the motives for condom use or non-use during casual sex. METHODS: A
      cross-sectional study was performed on a sample of 900 participants, 524 males
      and 376 females. All participants were 15-29 (20.93 +/- 4.071) years of age and
      came from four different centres (a university, two secondary schools, and a
      military base) in Melilla (Spain). The participants were given a socio
      demographic survey as well as a psychometric text on high-risk sexual behaviour.
      RESULTS: The results found gender-based significant differences for sexual
      relations with penetration (p = 0.001), number of sexual partners (p = 0.001),
      and sexual relations with casual partners (p = 0.001). In all of these variables,
      male participants had higher percentages than female participants. Reasons for
      having casual sexual relations were also different for men and women, differences
      were found for the items, opportunity (p = 0.001), interest in knowing the other
      person (p = 0.015), physical excitement (p = 0.056) and drug consumption (p =
      0.059). Regarding the reasons for consistent condom use with casual partners,
      there were differences for the item, my demand of a condom (p = 0.002). For the
      non-use of condoms with casual partners, differences were found for the items, I
      do not like to use condoms (p = 0.001) and condoms lessen sensitivity and reduce
      pleasure (p = 0.009). CONCLUSIONS: Men and women were found to have different
      high-risk sexual behaviours and practices. Of the motives for having sexual
      relations with casual partners, male participants considered opportunity and
      interest in knowing the other person to be more important than the female
      participants. Regarding condom use, the female participants' demand to use a
      condom was a significant gender-based difference. In contrast to the young women,
      the male participants mostly justified not using a condom because it lessened
      sensitivity and reduced pleasure.

PMID- 25053252
TI  - The Maize TFome--development of a transcription factor open reading frame
      collection for functional genomics.
AB  - Establishing the architecture of the gene regulatory networks (GRNs) responsible
      for controlling the transcription of all genes in an organism is a natural
      development that follows elucidation of the genome sequence. Reconstruction of
      the GRN requires the availability of a series of molecular tools and resources
      that so far have been limited to a few model organisms. One such resource
      consists of collections of transcription factor (TF) open reading frames (ORFs)
      cloned into vectors that facilitate easy expression in plants or microorganisms.
      In this study, we describe the development of a publicly available maize TF ORF
      collection (TFome) of 2034 clones corresponding to 2017 unique gene models in
      recombination-ready vectors that make possible the facile mobilization of the TF
      sequences into a number of different expression vectors. The collection also
      includes several hundred co-regulators (CoREGs), which we classified into well
      defined families, and for which we propose here a standard nomenclature, as we
      have previously done for TFs. We describe the strategies employed to overcome the
      limitations associated with cloning ORFs from a genome that remains incompletely
      annotated, with a partial full-length cDNA set available, and with many TF/CoREG
      genes lacking experimental support. In many instances this required the
      combination of genome-wide expression data with gene synthesis approaches. The
      strategies developed will be valuable for developing similar resources for other
      agriculturally important plants. Information on all the clones generated is
      available through the GRASSIUS knowledgebase (http://grassius.org/). 

PMID- 25053254
TI  - Disruption of structural and functional networks in long-standing multiple
      sclerosis.
AB  - Both gray matter atrophy and disruption of functional networks are important
      predictors for physical disability and cognitive impairment in multiple sclerosis
      (MS), yet their relationship is poorly understood. Graph theory provides a
      modality invariant framework to analyze patterns of gray matter morphology and
      functional coactivation. We investigated, how gray matter and functional networks
      were affected within the same MS sample and examined their interrelationship.
      Magnetic resonance imaging and magnetoencephalography (MEG) were performed in 102
      MS patients and 42 healthy controls. Gray matter networks were computed at the
      group-level based on cortical thickness correlations between 78 regions across
      subjects. MEG functional networks were computed at the subject level based on the
      phase-lag index between time-series of regions in source-space. In MS patients,
      we found a more regular network organization for structural covariance networks
      and for functional networks in the theta band, whereas we found a more random
      network organization for functional networks in the alpha2 band. Correlation
      analysis revealed a positive association between covariation in thickness and
      functional connectivity in especially the theta band in MS patients, and these
      results could not be explained by simple regional gray matter thickness
      measurements. This study is a first multimodal graph analysis in a sample of MS
      patients, and our results suggest that a disruption of gray matter network
      topology is important to understand alterations in functional connectivity in MS
      as regional gray matter fails to take into account the inherent connectivity
      structure of the brain.

PMID- 25053255
TI  - Ram seminal plasma proteome and its impact on liquid preservation of spermatozoa.
AB  - Seminal plasma is composed of secretions from the epididymis and the accessory
      sex glands and plays a critical role in the fertilising ability of spermatozoa.
      In rams, analysis of seminal plasma by GeLC-MS/MS has allowed the identification
      of more than 700 proteins, including a high abundance of Binder of Sperm family
      proteins (BSP1, BSP5, SPADH1, SPADH2), the spermadhesin family (bodhesin2),
      lactoferrin and newly identified proteins like UPF0762 (C6orf58 gene). When
      spermatogenesis was stopped by scrotal insulation, changes in the proteome
      profile revealed the sperm origin of 40 seminal proteins, such as glycolysis
      pathway enzymes, the chaperonin containing TCP1 (CCT) complex and the 26S
      proteasome complex. Sperm mobility after liquid preservation (24h in milk at 15
      degrees C) is male dependent and can be correlated to differences in the seminal
      plasma proteome, detected by spectral counting. The negative association of zinc
      alpha-2 glycoprotein (ZAG) with semen preservation was confirmed by the use of
      recombinant human ZAG, which induced an increase in mobility of fresh sperm, but
      then decreased sperm mobility after 24h of incubation. Several sperm membrane
      proteins interacting with the cytoskeleton, glycolysis enzymes and sperm
      associated proteins involved in capacitation correlated with better liquid
      storage and can be considered as seminal biomarkers of sperm preservation.
      BIOLOGICAL SIGNIFICANCE: Extensive analysis of the ram seminal plasma proteome
      reveals a complex and diverse protein composition. This composition varies
      between males with different sperm preservation abilities. Several proteins were
      shown to originate from the spermatozoa and positively correlate with sperm
      liquid preservation, indicating that these proteins can be traced as sperm
      biomarkers within the seminal plasma. The zinc alpha-2 glycoprotein (ZAG) was
      found to have a biphasic effect on sperm mobility, with a short-term stimulation
      followed by a long-term exhaustion of sperm mobility after a 24h preservation
      period.

PMID- 25053256
TI  - Whose problem is it anyway? Crimes against women in India.
AB  - The recent public outcry following a brutal gang rape of a young woman in India's
      national capital was a watershed moment in the world's largest democracy. It
      generated widespread public and political support for strengthening legal
      provisions to punish sex offenders. Although the legal response is a useful
      deterrent against such heinous crimes, women continue to suffer due to deeply
      rooted social prejudices that make them vulnerable to violence and discrimination
      in society. In this commentary, we aim to analyse the current developments with
      respect to gender violence in India within a background of the social position of
      women in Indian society. Using secondary data related to sex-selective abortions
      and crimes against women, and a critical review of the portrayal of women in
      Indian cinema, we reflect on the role of health workers, researchers and public
      health professionals in shaping a social response towards improving gender parity
      in our country. 

PMID- 25053257
TI  - Seizure activity occurs in the collagenase but not the blood infusion model of
      striatal hemorrhagic stroke in rats.
AB  - Seizures are a frequent complication of brain injury, including intracerebral
      hemorrhage (ICH), where seizures occur in about a third of patients. Rodents are
      used to study pathophysiology and neuroprotective therapies after ICH, but there
      have been no studies assessing the occurrence of seizures in these models. Thus,
      we compared seizure incidence and characteristics after infusing collagenase
      (0.14 U), which degrades blood vessels, and autologous blood (100 MUL) into the
      striatum of rats. Saline was infused in others as a negative control, whereas
      iron, a by-product of degrading erythrocytes, served as a positive control.
      Ipsilateral and contralateral electroencephalographic (EEG) activity was
      continuously monitored with telemetry probes for a week after the stroke. There
      were no electrographic abnormalities during baseline recordings. As expected,
      saline did not elicit any epileptiform activity whereas iron caused seizure
      activity. Seizures occurred in 66 % of the collagenase group between 10 and 36 h,
      their duration ranged from 5 to 90 s, and these events were mostly observed
      bilaterally. No such activity occurred after blood infusion despite comparable
      lesion sizes of 32.5 and 40.9 mm(3) in the collagenase and blood models,
      respectively (p = 0.222). Therefore, seizures are a common acute occurrence in
      the collagenase but not whole blood models of striatal ICH (p = 0.028, for
      incidence). These findings have potential implications for ICH studies such as
      for understanding model differences, helping select which model to use, and
      determining how seizures may affect or be affected by treatments applied after
      stroke.

PMID- 25053258
TI  - Full steam ahead with remote ischemic conditioning for stroke.

PMID- 25053259
TI  - Fetal growth and cardio-metabolic risk factors in the 20-year-old offspring.
AB  - OBJECTIVE: To investigate the association between prenatal growth patterns as
      estimated by biparietal diameter and cardio-metabolic risk at 20 years. DESIGN:
      Follow-up study. SETTING: Denmark 1988-2009. POPULATION: Two cohorts of children
      born between 1988 and 1990 (n=707) and followed up in 2008-2009 (n=333-509).
      METHODS: We have access to biparietal diameter from early ultrasound scan and
      birthweight. For each gender, biparietal diameter and birthweight, gestational
      age-specific growth-z-scores were calculated. A change in growth trajectory was
      depicted as a shift in z-score for the two growth measures. Multiple linear
      regression modeling was used to estimate associations between biparietal diameter
      and birthweight z-scores and later cardio-metabolic risk factors as well as
      estimating whether changing growth trajectory was associated with later cardio
      metabolic risk. MAIN OUTCOME MEASURES: Self-reported anthropometrics and
      clinically measured blood pressure, heart rate and biochemical measures
      associated with cardio-metabolic health. RESULTS: After adjustments, biparietal
      diameter was not associated with any of the outcomes. Birthweight was positively
      associated with both adult height and weight and inversely associated with
      insulin, triglyceride and insulin resistance. Also, the data indicated a U-shaped
      association between growth in the second half of pregnancy and adult body mass
      index among individuals with a low biparietal diameter in mid-pregnancy.
      CONCLUSION: Different patterns of intrauterine growth may be associated with
      later risk of cardio-metabolic disease.

PMID- 25053260
TI  - Malignant epithelial tumors observed in hernia sacs.
AB  - INTRODUCTION: The study of a hernia sac rarely provides the evidence of a primary
      or metastatic malignant epithelial tumor. METHODS: We have reviewed our
      institutional experience with malignant epithelial tumors found in a hernia sac
      with the purpose of evaluating cases present/manifesting in the sac, gross
      appearance, histologic type, primary tumor sites, staging, and patient outcome.
      RESULTS: A total of 8,435 adult patients underwent inguinal, femoral, umbilical
      or abdominal hernia repair in our hospitals. Twelve (0.14 %) patients had a
      malignant epithelial tumor in the hernia sac. Only one of these tumors was
      primary and the rest metastatic. Six out of twelve tumors (50.0 %), all of them
      metastatic, were discovered after hernia repair (0.07 %). The mean age of the 12
      patients was 68.7 +/- 15.2 years (range 43-90 years). Eight patients were male
      (66.7 %). Six tumors were located in inguinal (50.0 %), five in umbilical (41.7
      %), and one in abdominal (8.3 %) hernia sacs. Gastrointestinal cases comprised
      50.0 % and gynaecologic cases 25 % of tumors. In three cases (25.0 %) the hernia
      sac showed no gross abnormalities. All tumors were found in an advanced stage of
      development and ten patients died. Mean survival of these patients after hernia
      repair was 275.1 +/- 376.4 days (range 6-1,095 days; median 68 days).
      CONCLUSIONS: Gravity, inflammatory oncotaxis, and chemotactic agents are probably
      operative phenomena in the development of metastatic lesions in hernia sacs.
      Routine microscopic evaluation of hernia sacs is not justified by the high cost.
      It should be reserved for selected cases based on the gross findings. Since
      subtle lesions may be overlooked on gross examination, particular caution should
      be taken with the examination of hernia sacs from older patients.

PMID- 25053261
TI  - Celebrating the strengths of black youth: increasing self-esteem and implications
      for prevention.
AB  - The purpose of this study was to test the impact of a preventive intervention
      program, celebrating the strengths of black youth (CSBY), on African American
      children's self-esteem, racial identity, and parental racial socialization
      messages. CSBY consisted of 10 in-person group sessions in which small groups of
      middle school students met two trained group leaders. Parents were invited to
      attend three of the 10 group sessions. African American children between the ages
      of 7 and 10 were randomly assigned to either a treatment (TX; n = 33) or waitlist
      control (WLC; n = 40) group. Pre- and post-measures were completed to capture
      treatment effects. Analyses revealed that treatment group participants had higher
      levels of self-esteem post intervention than WLC group participants. In addition,
      treatment group parents were more likely to communicate egalitarian messages to
      their children post intervention than WLC parents. The advantages of a cultural
      heritage, strengths-based preventive intervention for African American youth and
      suggestions for future research are discussed.

PMID- 25053262
TI  - After the 2010 guidelines: less fear and more cardiopulmonary resuscitation.

PMID- 25053263
TI  - Retention of knowledge and skills after Advanced Cardiovascular Life Support
      courses.

PMID- 25053264
TI  - Limited yield of hospitalization for the evaluation of syncope in patients
      presenting to an urban tertiary medical center.
AB  - Syncope is a frequent presenting complaint in the emergency department and is
      associated with significant medical costs. We examined the utility of inpatient
      evaluation of syncope for patients in whom a diagnosis was not established in the
      emergency department. We retrospectively reviewed consecutive patients presenting
      with syncope to an urban tertiary care medical center. A diagnosis was not
      established after initial evaluation in the emergency department in 171 of 230
      patients admitted. Inhospital evaluation led to a diagnosis in 26 patients. Acute
      intervention was required in 2 patients. Our observations suggest that an
      inpatient evaluation of syncope for patients in whom a diagnosis is not made on
      initial evaluation is of low yield, and outpatient follow-up may be safe. 

PMID- 25053265
TI  - Fusiform aneurysm of a persistent trigeminal artery associated with rare
      intracranial arterial variations and subarachnoid hemorrhage.
AB  - The trigeminal artery is one of four primitive anastomoses between the internal
      carotid artery and vertebrobasilar system that regresses in the sixth week of
      fetal development. A persistent trigeminal artery (PTA) is generally an
      incidental finding but may also be associated with intracranial vascular
      pathologies such as aneurysms, arteriovenous malformations, and cranial nerve
      compression syndromes. We present an extremely rare case of a right PTA with an
      associated bleeding fusiform aneurysm located in the carotidian (lateral) part of
      the PTA. In addition, this rare anatomic variation was associated with bilateral
      absence of the posterior communicating arteries, a left posterior cerebral artery
      originating from the left internal carotid artery, and agenesis of the A1 segment
      of the left anterior cerebral artery. 

PMID- 25053266
TI  - The geographic distribution of onchocerciasis in the 20 participating countries
      of the African Programme for Onchocerciasis Control: (1) priority areas for
      ivermectin treatment.
AB  - BACKGROUND: The African Programme for Onchocerciasis Control (APOC) was created
      to control onchocerciasis as a public health problem in 20 African countries. Its
      main strategy is community directed treatment with ivermectin. In order to
      identify all high risk areas where ivermectin treatment was needed, APOC used
      Rapid Epidemiological Mapping of Onchocerciasis (REMO). REMO has now been
      virtually completed and we report the results in two articles. The present
      article reports the mapping of high risk areas where onchocerciasis was a public
      health problem. The companion article reports the results of a geostatistical
      analysis of the REMO data to map endemicity levels and estimate the number
      infected. METHODS: REMO consists of three stages: exclusion of areas that are
      unsuitable for the vector, selection of sample villages to be surveyed in each
      river basin, and examination of 30 to 50 adults for the presence of palpable
      onchocercal nodules in each selected village. The survey results and other
      relevant information were processed in a geographical information system. A panel
      of experts interpreted the data taking the river-based sampling into account and
      delineated high risk areas where the prevalence of nodules is greater than 20%.
      RESULTS: Unsuitable areas were identified in eight countries. In the remaining
      areas surveys were done in a total of 14,473 sample villages in which more than
      half a million people were examined. High-risk areas were identified in 18 APOC
      countries, ranging from small isolated foci to a vast contiguous endemic area of
      2 million km2 running across seven countries. In five countries the high risk
      area covered more than 48% of the total surface area, and 31% to 48% of the
      population. It is estimated that 86 million people live in high risk areas in the
      APOC countries. CONCLUSIONS: The REMO maps have played a significant role in
      onchocerciasis control in the 20 APOC countries. All high-risk areas where
      onchocerciasis used to be a serious public health problem have been clearly
      delineated. This led to the creation of community-directed treatment projects
      that by 2012 were providing annual ivermectin treatment to over 80 million
      people.

PMID- 25053267
TI  - Attempts at validating a recombinant Flavobacterium psychrophilum gliding
      motility protein N as a vaccine candidate in rainbow trout, Oncorhynchus mykiss
      (Walbaum) against bacterial cold-water disease.
AB  - The Flavobacterium psychrophilum gliding motility N (GldN) protein was
      investigated to determine its ability to elicit antibody responses and provide
      protective immunity in rainbow trout Oncorhynchus mykiss (Walbaum). GldN was PCR
      amplified, cloned into pET102/D-TOPO, and expressed in Escherichia coli. Bacteria
      expressing recombinant GldN (rGldN) were formalin-inactivated and injected
      intraperitoneally (i.p.) into rainbow trout with Freund's complete adjuvant (FCA)
      in four separate studies that used two different immunization protocols followed
      by challenge evaluations. Fish injected with E. coli only in FCA served as the
      control. Antibody responses to F. psychrophilum whole-cell lysates measured by
      ELISA were low in all four studies. Protection against F. psychrophilum challenge
      was observed in the first study, but not in the three following studies. The
      discrepancies in results obtained in the later studies are unclear but may relate
      to formalin treatment of the antigen preparations. Overall, it appeared that
      rGldN delivered i.p. as a crude formalin-killed preparation is not a consistent
      vaccine candidate, and more work is required. Additionally, this study
      illustrates the importance of conducting multiple in vivo evaluations on
      potential vaccine(s) before any conclusions are drawn. 

PMID- 25053268
TI  - Antimicrobial drug use in Austrian pig farms: plausibility check of electronic on
      farm records and estimation of consumption.
AB  - Electronic drug application records from farmers from 75 conventional pig farms
      were revised and checked for their plausibility. The registered drug amounts were
      verified by comparing the farmers' records with veterinarians' dispensary
      records. The antimicrobial consumption was evaluated from 2008 to 2011 and
      expressed in weight of active substance(s), number of used daily doses (nUDD),
      number of animal daily doses (nADD) and number of product-related daily doses
      (nPrDD). All results were referred to one year and animal bodyweight (kg
      biomass). The data plausibility proof revealed about 14 per cent of unrealistic
      drug amount entries in the farmers' records. The annual antimicrobial consumption
      was 33.9 mg/kg/year, 4.9 UDDkg/kg/year, 1.9 ADDkg/kg/year and 2.5 PrDDkg/kg/year
      (average). Most of the antimicrobials were applied orally (86 per cent) and at
      group-level. Main therapy indications were metaphylactic/prophylactic measures
      (farrow-to-finish and fattening farms) or digestive tract diseases (breeding
      farms). The proportion of the 'highest priority critically important
      antimicrobials' was low (12 per cent). After determination of a threshold value,
      farms with a high antimicrobial use could be detected. Statistical tests showed
      that the veterinarian had an influence on the dosage, the therapy indication and
      the active substance. Orally administered antimicrobials were mostly underdosed,
      parenterally administered antimicrobials rather correctly or overdosed. 

PMID- 25053269
TI  - Patellar ligament rupture in the dog: repair methods and patient outcomes in 43
      cases.
AB  - The medical records of dogs receiving surgery for unilateral patellar ligament
      rupture between 1999 and 2012 at 12 multidisciplinary referral centres were
      reviewed. Forty-three cases were identified; 26 were traumatic in origin; almost
      one-third were iatrogenic, of which over three-quarters occurred as a
      complication following surgical stabilisation of patellar luxation. Treatment
      involved primary reapposition of the ligament (36 cases). The repair was
      protected by circumpatellar and/or transpatellar loop(s) of orthopaedic wire,
      nylon, polypropylene or polydioxanone suture (34 cases). Wire loops were more
      likely to require surgical removal compared with loops of other materials
      (P=0.0014). The stifle joint was immobilised postoperatively by the applications
      of a transarticular external skeletal fixator (taESF) in 17 cases and by external
      coaptation (EC) in 8 cases; in 18 cases, no postoperative joint immobilisation
      was provided. Complications specific to the method of immobilisation occurred in
      seven of the cases with taESF and six of the cases with EC. Revision surgery to
      address failure of repair was required in five cases. Outcome was classified as
      acceptable or good in over three-quarters of the cases (31/40) and poor in less
      than a quarter (9/40). These data highlight patellar ligament rupture as a
      complication of surgical stabilisation of patellar luxation. 

PMID- 25053270
TI  - Efficacy of a new attenuated duck parvovirosis vaccine in Muscovy ducks.
AB  - The efficacy of a new live attenuated parvovirosis vaccine was tested in
      conventional ducklings against Derzsy's disease by comparing two vaccination
      regimens. Ducklings were vaccinated with either one injection at 17 days of age
      or two injections at 1 and 17 days of age. Controls and vaccinated ducklings were
      challenged with a virulent Derzsy strain at 21 days of age (day 20). Weight was
      measured on days 20, 34 and 42/43. Surviving birds were necropsied on day 42/43.
      Protection rates were significantly higher in the groups vaccinated once (90 per
      cent, P=0.003) and twice (95 per cent, P<0.001) than in the control group (59 per
      cent). The bodyweight was significantly higher in both vaccinated groups than in
      the control group on day 34 (P=0.008 and P<0.001, respectively) and day 42/43
      (P<0.001 for both groups). The growth was significantly higher in the group
      vaccinated twice than the group vaccinated once on day 34 (P=0.047) and day 42/43
      (P=0.017). Both vaccination regimens provided a quick onset of immunity. The
      higher weight gain in the group vaccinated twice suggests that an early
      vaccination at hatchery followed by a second injection at 17 days of age is an
      optimal and practical schedule to prevent parvovirosis. 

PMID- 25053271
TI  - Self-assembly and modified luminescence properties of NaY(MoO4)2:Tb3+, Eu3+
      inverse opals.
AB  - Three-dimensional (3D) inverse opal photonic crystals can not only modulate the
      emissions of the inserted emitters, they also have the advantage of a large
      surface to volume ratio, which permits their use in noninvasive fluorescence
      detection. In this work, novel NaY(MoO4)2:Eu(3+) and NaY(MoO4)2:Tb(3+), Eu(3+)
      inverse opals were synthesized using a polymethylmethacrylate (PMMA) template by
      the sol-gel method. It was observed that the photoluminescence (PL) intensity and
      spontaneous decay rates (SDRs) of the inverse opals were suppressed, in contrast
      to the corresponding ground reference (REF) samples, due to the modulation of the
      effective refractive index (n(eff)). The concentration quenching of Eu(3+) and
      energy transfer from Tb(3+) to Eu(3+) were suppressed, due to the periodic empty
      cavity structure of the inverse opals.

PMID- 25053272
TI  - Detection of T-wave beat-by-beat variations prior to ventricular arrhythmias
      onset in ICD-stored intracardiac electrograms: the Endocardial T-Wave Alternans
      Study (ETWAS).
AB  - BACKGROUND: The aim of the Endocardial T-Wave Alternans Study was to
      prospectively assess the presence of T-wave alternans (TWA) or beat-to-beat
      repolarization changes on implantable cardioverter-defibrillator (ICD)-stored
      electrograms (EGMs) immediately preceding the onset of spontaneous ventricular
      tachycardia (VT) or fibrillation (VF). METHODS: Thirty-seven VT/VF episodes were
      compared to 116 baseline reference EGMs from the same 57 patients. A Bayesian
      model was used to estimate the T-wave waveform in each cardiac beat and a set of
      10 parameters was selected to segment each detected T wave. Beat-by-beat
      differences in each T-wave parameter were computed using the absolute value of
      the difference between each beat and the following one. Fisher criterion was used
      for determining the most discriminant T-wave parameters, then top-M ranked
      parameters yielding a normalized cumulative Fisher score > 95% were selected, and
      analysis was applied on these selected parameters. Simulated TWA EGMs were used
      to validate the algorithm. RESULTS: In the simulation study, TWA was detectable
      even in the case of the smallest simulated alternans of 25 MUV. In 13 of the 37
      episodes (35%) occurring in nine of 16 patients, significant larger beat-to-beat
      variations before arrhythmia onset were detected compared to their respective
      references (median one positive episode per patient). Parameters including the T
      wave apex amplitude seem the more discriminant parameters. CONCLUSIONS: Detection
      of beat-by-beat repolarization variations in ICD-stored EGMs is feasible in a
      significant subset of cases and may be used for predicting the onset of
      ventricular arrhythmias.

PMID- 25053274
TI  - Improving clinician competency in communication about schizophrenia: a pilot
      educational program for psychiatry trainees.
AB  - OBJECTIVE: Important gaps are observed in clinicians' communication with patients
      and families about psychiatric disorders such as schizophrenia. Communication
      skills can be taught, and models for education in these skills have been
      developed in other fields of medicine, such as oncology, providing a framework
      for training communication skills relevant to psychiatric practice. This study
      evaluated a pilot communication skills education program for psychiatry trainees,
      focusing on discussing schizophrenia diagnosis and prognosis. METHOD:
      Communication skills training modules were developed based on an existing
      theoretical framework (ComSkil), adapted for discussing a schizophrenia diagnosis
      and prognosis. Pre-post training rating of self-reported confidence in a range of
      communication tasks was obtained, along with trainee views on the training
      methods. RESULTS: Thirty-eight participants completed the training. Significant
      improvements in confidence were reported post training for discussing
      schizophrenia prognosis, including an increased capacity to critically evaluate
      their own communication skills. Participants reported high levels of satisfaction
      with the program. CONCLUSION: This preliminary study provides support for the
      translation of a well-established educational model to psychiatric training
      addressing core clinical communication tasks and provides the foundation for the
      development of a more comprehensive evaluation and an extended curriculum
      regarding other aspects of care for patients with schizophrenia: ongoing
      management and recovery, dealing with conflict, and conducting a family
      interview.

PMID- 25053275
TI  - Experiences of HIV-related stigma among HIV-positive older persons in Uganda--a
      mixed methods analysis.
AB  - There is limited data on stigma among older HIV-infected adults in sub-Saharan
      Africa. We describe the experiences of stigma and disclosure in a cohort of HIV
      positive older people in Uganda. Using data from the Wellbeing of Older Peoples'
      Study of Kalungu (rural site) and Wakiso district (peri-urban site) residents, we
      measured self-reported stigma levels for 183 respondents (94 on antiretroviral
      therapy (ART); 88, not on ART) using a stigma score generated using three
      questions on stigma perceptions where 0 meant no stigma at all and 100 was
      maximum stigma. Based on two questions on disclosure, an overall score was
      computed. High disclosure was assigned to those who often or very often disclosed
      to the family and were never or seldom afraid to disclose elsewhere. We examined
      the experiences of HIV stigma of 25 adults (52% females) using semi-structured,
      open-ended interviews and monthly oral diaries over one year. Mean age of the
      respondents was 70 years (range 60-80 years) and 80% of all respondents were
      enrolled in ART. Interview transcripts were analysed using thematic content
      analysis. Overall, 55% of respondents had a high disclosure score, meaning they
      disclosed easily, and 47% had a high stigma score. The stigma scores were similar
      among those with high and low disclosure scores. In multivariate analyses with
      disclosure and stigma scores as dependent variables none of the respondents'
      characteristics had a significant effect at the 5% level. Qualitative data
      revealed that stigma ranges from: (1) perceptions (relatively passive, but
      leading to behaviour such as gossip, especially if not intended maliciously); to
      (2) discriminatory behaviour (active or enacted stigma; from malicious gossip to
      outright discrimination). Despite the relatively high levels of disclosure, older
      people suffer from high levels of stigma of various forms apart from HIV-related
      stigma. Efforts to assess for different forms of stigma at an individual level
      deserve greater attention from service providers and researchers, and must be
      context specific.

PMID- 25053276
TI  - Hypothesis: Concordance of Gaucher disease and large granular lymphocytic
      leukemia has biological plausibility.

PMID- 25053277
TI  - First report on the antibody verification of MICA epitopes recorded in the HLA
      epitope registry.
AB  - The International Registry of HLA Epitopes (http://epregistry.com.br) has been
      recently established as a tool to understand antibody responses to HLA
      mismatches. These epitopes are defined structurally by three-dimensional
      molecular modelling and amino acid sequence differences between HLA antigens. A
      major goal was to identify HLA epitopes that have been verified experimentally
      with informative antibodies. This report addresses the identification of MICA
      epitopes. Our analysis included published information about MICA antibody
      reactivity in sera from sensitized patients as well as data from our own
      laboratories. This report describes twenty-one MICA epitopes verified with
      antibodies which have primarily been tested in Luminex assays with single
      alleles. The epitopes correspond to distinct eplets that are often defined by
      single residues. The Registry is still a work-in-progress and will become a
      useful resource for HLA professionals interested in histocompatibility testing at
      the epitope level and investigating antibody responses to HLA mismatches in
      transplant patients. 

PMID- 25053278
TI  - Prevalence of women with early-stage breast cancer receiving active management
      using electronic health records from oncology clinics in the United States.
AB  - The purpose of this study was to estimate the prevalence of women receiving
      treatment or active surveillance for stage I-III breast cancer in the United
      States from 2009 to 2012, stratified by patient age and tumor characteristics. In
      each study year, electronic medical records were used to identify women aged >=18
      years with stage I-III breast cancer and treated or under active surveillance
      (>=4 visits) at an oncology clinic that contributes data to the Oncology Services
      Comprehensive Electronic Records database. Prevalence was projected to the
      national level overall and within strata (by tumor characteristics, year of
      breast cancer diagnosis, and age). We identified 5,219 female breast cancer
      patients (18 % <age 50; 58 % <age 65) representing 787,082 (95 % CI 778,012
      796,153) women in the US in 2012. At diagnosis, 44 % had stage I, 42 % stage II,
      and 14 % stage III disease; 69 % had estrogen receptor (ER) and progesterone
      receptor (PR) expression-positive tumors; 19 % were ER- and PR-negative; and 14 %
      had triple-negative phenotype (ER-, PR-, and HER2-negative). Overall 56 % of
      patients received treatment in 2012, 22 % chemotherapy, 8 % biologic therapy, and
      36 % endocrine therapy. Treatment prevalence was higher among younger patients
      and at more advanced disease stages. Approximately half of women with ER
      negative, PR-positive, HER2-negative, or triple-negative tumors received
      chemotherapy. As a conclusion, in 2012, approximately 800,000 women in the US
      were under treatment or active surveillance for early-stage breast cancer.
      Treatment prevalence differed by patient age, disease stage, and tumor histology.

PMID- 25053279
TI  - The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement
      and dopamine overflow in the frontal cortex.
AB  - Relapse represents one of the most significant problems in the long-term
      treatment of drug addiction. Cocaine blocks plasma membrane monoamine
      transporters and increases dopamine (DA) overflow in the brain, and DA is
      critical for the motivational and primary reinforcing effects of the drug as well
      as cocaine-primed reinstatement of cocaine seeking in rats, a model of relapse.
      Thus, modulators of the DA system may be effective for the treatment of cocaine
      dependence. The endogenous neuropeptide galanin inhibits DA transmission, and
      both galanin and the synthetic galanin receptor agonist, galnon, interfere with
      some rewarding properties of cocaine. The purpose of this study was to further
      assess the effects of galnon on cocaine-induced behaviors and neurochemistry in
      rats. We found that galnon attenuated cocaine-induced motor activity,
      reinstatement and DA overflow in the frontal cortex at a dose that did not reduce
      baseline motor activity, stable self-administration of cocaine, baseline
      extracellular DA levels or cocaine-induced DA overflow in the nucleus accumbens
      (NAc). Similar to cocaine, galnon had no effect on stable food self
      administration but reduced food-primed reinstatement. These results indicate that
      galnon can diminish cocaine-induced hyperactivity and relapse-like behavior,
      possibly in part by modulating DA transmission in the frontal cortex. 

PMID- 25053280
TI  - The prevalence of encoded digital trace evidence in the nonfile space of computer
      media(,) (.).
AB  - Forensically significant digital trace evidence that is frequently present in
      sectors of digital media not associated with allocated or deleted files. Modern
      digital forensic tools generally do not decompress such data unless a specific
      file with a recognized file type is first identified, potentially resulting in
      missed evidence. Email addresses are encoded differently for different file
      formats. As a result, trace evidence can be categorized as Plain in File (PF),
      Encoded in File (EF), Plain Not in File (PNF), or Encoded Not in File (ENF). The
      tool bulk_extractor finds all of these formats, but other forensic tools do not.
      A study of 961 storage devices purchased on the secondary market and shows that
      474 contained encoded email addresses that were not in files (ENF). Different
      encoding formats are the result of different application programs that processed
      different kinds of digital trace evidence. Specific encoding formats explored
      include BASE64, GZIP, PDF, HIBER, and ZIP. 

PMID- 25053281
TI  - Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic
      association reveals novel candidate genes for bipolar disorder.
AB  - OBJECTIVES: Breakpoints of chromosomal abnormalities facilitate identification of
      novel candidate genes for psychiatric disorders. Genome-wide significant evidence
      supports the linkage between chromosome 17q25.3 and bipolar disorder (BD). Co
      segregation of translocation t(9;17)(q33.2;q25.3) with psychiatric disorders has
      been reported. We aimed to narrow down these chromosomal breakpoint regions and
      to investigate the associations between single nucleotide polymorphisms within
      these regions and BD as well as schizophrenia (SZ) in large genome-wide
      association study samples. METHODS: We cross-linked Danish psychiatric and
      cytogenetic case registers to identify an individual with both
      t(9;17)(q33.2;q25.3) and BD. Fluorescent in situ hybridization was employed to
      map the chromosomal breakpoint regions of this proband. We accessed the
      Psychiatric Genomics Consortium BD (n = 16,731) and SZ (n = 21,856) data. Genetic
      associations between these disorders and single nucleotide polymorphisms within
      these breakpoint regions were analysed by BioQ, FORGE, and RegulomeDB programmes.
      RESULTS: Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal
      pentraxin I (NPTX1), ring finger protein 213 (RNF213), and regulatory-associated
      protein of mammalian target of rapamycin (mTOR) (RPTOR)] were found to be located
      within the 17q25.3 breakpoint region. NPTX1 was significantly associated with BD
      (p = 0.004), while ENDOV was significantly associated with SZ (p = 0.0075) after
      Bonferroni correction. CONCLUSIONS: Prior linkage evidence and our findings
      suggest NPTX1 as a novel candidate gene for BD.

PMID- 25053282
TI  - Heavy metal accumulation and histomorphological alterations in Aphanius fasciatus
      (Pisces, Cyprinodontidae) from the Gulf of Gabes (Tunisia).
AB  - The present study illustrates an analysis of histological changes; cadmium (Cd),
      copper (Cu) and zinc (Zn) accumulation; and metallothionein (MT) levels in normal
      and deformed Mediterranean killifish, Aphanius fasciatus (Pisces,
      Cyprinodontidae), collected from unpolluted (S1) and polluted areas (S2) in the
      Gulf of Gabes in Tunisia. Metal determination in water and sediment showed that
      the concentrations were significantly higher (p < 0.0001) in S2 compared to S1.
      Deformed fish showed a significantly higher accumulation of Cd, Cu, and Zn and
      high levels of MTs in their tissues compared to normal ones. Histopathological
      investigations revealed greater changes in gills, kidney, liver, and bone tissues
      of fish from the polluted area than those recorded in fish from the reference
      area. In comparison to normal fish of the polluted area (S2), tissue alterations
      were more developed in deformed specimens of this site. A possible relationship
      between metallic pollution, incidence of spinal deformities, and histological
      changes in A. fasciatus in the polluted site was discussed.

PMID- 25053283
TI  - Diversity and characterization of culturable bacterial endophytes from Zea mays
      and their potential as plant growth-promoting agents in metal-degraded soils.
AB  - In this study, we evaluated the phylogenetic diversity of culturable bacterial
      endophytes of Zea mays plants growing in an agricultural soil contaminated with
      Zn and Cd. Endophytic bacterial counts were determined in roots and shoots, and
      isolates were grouped by random amplified polymorphic DNA and identified by 16S
      ribosomal RNA (rRNA) gene sequencing. Endophytes were further characterized for
      the production of plant growth-promoting (PGP) substances, such as NH3,
      siderophores, indol-3-acetic acid (IAA), hydrogen cyanide and extracellular
      enzymes, and for the capacity to solubilize phosphate. The endophytes producing
      higher amounts of IAA were screened for their tolerance to Zn and Cd and used as
      bioinoculants for maize seedlings grown in the Zn/Cd-contaminated soil. The
      counts of endophytes varied between plant tissues, being higher in roots (6.48
      log10 g(-1) fresh weight) when compared to shoots (5.77 log10 g(-1) fresh
      weight). Phylogenetic analysis showed that endophytes belong to three major
      groups: alpha-Proteobacteria (31 %), gamma-Proteobacteria (26 %) and
      Actinobacteria (26 %). Pseudomonas, Agrobacterium, Variovorax and Curtobacterium
      were among the most represented genera. Endophytes were well-adapted to high
      Zn/Cd concentrations (up to 300 mg Cd l(-1) and 1,000 mg Zn l(-1)) and showed
      ability to produce several PGP traits. Strains Ochrobactrum haematophilum ZR 3-5,
      Acidovorax oryzae ZS 1-7, Frigoribacterium faeni ZS 3-5 and Pantoea allii ZS 3-6
      increased root elongation and biomass of maize seedlings grown in soil
      contaminated with Cd and Zn. The endophytes isolated in this study have potential
      to be used in bioremediation/phytoremediation strategies.

PMID- 25053284
TI  - Absorption and fluorescence properties of chromophoric dissolved organic matter:
      implications for the monitoring of water quality in a large subtropical
      reservoir.
AB  - The development of techniques for real-time monitoring of water quality is of
      great importance for effectively managing inland water resources. In this study,
      we first analyzed the absorption and fluorescence properties in a large
      subtropical reservoir and then used a chromophoric dissolved organic matter
      (CDOM) fluorescence monitoring sensor to predict several water quality parameters
      including the total nitrogen (TN), total phosphorus (TP), chemical oxygen demand
      (COD), dissolved organic carbon (DOC), and CDOM fluorescence parallel factor
      analysis (PARAFAC) components in the reservoir. The CDOM absorption coefficient
      at 254 nm (a(254)), the humic-like component (C1), and the tryptophan-like
      component (C3) decreased significantly along a gradient from the northwest to the
      lake center, northeast, southwest, and southeast region in the reservoir.
      However, no significant spatial difference was found for the tyrosine-like
      component (C2), which contributed only four marked peaks. A highly significant
      linear correlation was found between the a(254) and CDOM concentration measured
      using the CDOM fluorescence sensor (r(2) = 0.865, n = 76, p < 0.001), indicating
      that CDOM concentrations could act as a proxy for the CDOM absorption coefficient
      measured in the laboratory. Significant correlations were also found between the
      CDOM concentration and TN, TP, COD, DOC, and the maximum fluorescence intensity
      of C1, suggesting that the real-time monitoring of CDOM concentrations could be
      used to predict these water quality parameters and trace the humic-like
      fluorescence substance in clear aquatic ecosystems with DOC <2 mg/L and total
      suspended matter (TSM) concentrations <15 mg/L. These results demonstrate that
      the CDOM fluorescence sensor is a useful tool for on-line water quality
      monitoring if the empirical relationship between the CDOM concentration measured
      using the CDOM fluorescence sensor and the water quality parameters is calibrated
      and validated.

PMID- 25053285
TI  - Contrasting cellular stress responses of Baikalian and Palearctic amphipods upon
      exposure to humic substances: environmental implications.
AB  - The species-rich, endemic amphipod fauna of Lake Baikal does not overlap with the
      common Palearctic fauna; however, the underlying mechanisms for this are poorly
      understood. Considering that Palearctic lakes have a higher relative input of
      natural organic compounds with a dominance of humic substances (HSs) than Lake
      Baikal, we addressed the question whether HSs are candidate factors that affect
      the different species compositions in these water bodies. We hypothesized that
      interspecies differences in stress defense might reveal that Baikalian amphipods
      are inferior to Palearctic amphipods in dealing with HS-mediated stress. In this
      study, two key mechanisms of general stress response were examined: heat-shock
      protein 70 (HSP70) and multixenobiotic resistance-associated transporters
      (ABCB1). The results of quantitative polymerase chain reaction (qPCR) showed that
      the basal levels (in 3-day acclimated animals) of hsp70 and abcb1 transcripts
      were lower in Baikalian species (Eulimnogammarus cyaneus, Eulimnogammarus
      verrucosus, Eulimnogammarus vittatus-the most typical littoral species) than in
      the Palearctic amphipod (Gammarus lacustris-the only Palearctic species
      distributed in the Baikalian region). In the amphipods, the stress response was
      induced using HSs at 10 mg L(-1) dissolved organic carbon, which was higher than
      in sampling sites of the studied species, but well within the range (3-10 mg L(
      1)) in the surrounding water bodies populated by G. lacustris. The results of
      qPCR and western blotting (n = 5) showed that HS exposure led to increased
      hsp70/abcb1 transcripts and HSP70 protein levels in G. lacustris, whereas these
      transcript levels remained constant or decreased in the Baikalian species. The
      decreased level of stress transcripts is probably not able to confer an effective
      tolerance to Baikalian species against further environmental stressors in
      conditions with elevated HS levels. Thus, our results suggest a greater
      robustness of Palearctic amphipods and a higher sensitivity of Baikalian
      amphipods to HS challenge, which might prevent most endemic species from
      migrating to habitats outside Lake Baikal.

PMID- 25053286
TI  - Nitrate removal under different ecological remediation measures in Taihu Lake: a
      15N mass-balance approach.
AB  - Ecological remediation is an important measure for the protection of lake water
      quality in removing nutrients, such as nitrate (NO3 (-)). In this study, four
      bioremediation processes (bare sediment, immobilized nitrogen cycling bacteria
      (INCB) added, Elodea nuttallii added, E. nuttallii-INCB assemblage) were operated
      at a lab to elucidate the effect of macrophyte appearance and INCB addition on
      NO3 (-) removal and achieve the optimal processes for biomediation. (15) N-NO3
      solution was added to microcosms to identify the key nitrogen transformation
      processes responsible for NO3 (-) removal. Results showed that nitrate removal
      was significantly enhanced after the addition of INCB and E. nuttallii. In the
      treatments with INCB added, E. nuttallii added, and INCB and E. nuttallii-INCB
      assemblage, nitrate removal ratio achieved 94.74, 98.76, and 99.15 %,
      respectively. In contrast, only 23.47 % added nitrate was removed in the control.
      Plant uptake and denitrification played an important role in nitrogen removal.
      The water quality was substantially improved by the addition of INCB and
      macrophyte that can accelerate denitrification and promote nitrogen assimilation
      of plants. The results indicated that plant uptake and microbial denitrification
      were key processes for nitrate removal.

PMID- 25053287
TI  - Effect of lead treatment on medicarpin accumulation and on the gene expression of
      key enzymes involved in medicarpin biosynthesis in Medicago sativa L.
AB  - Lead (Pb) is the most common heavy metal contaminant in the environment. The
      present study was undertaken to determine the effect of Pb treatment on
      medicarpin production and accumulation in Medicago sativa L. To this aim, 7- and
      30-day-old plants were treated with 0, 120, 240, 500, and 1,000 MUM Pb during 10
      days. The content of medicarpin was determined by HPLC, and the extent of
      medicarpin production was deduced from the result of semiquantitative RT-PCR
      performed on PAL, CHS, and VR genes. HPLC results indicated that medicarpin
      concentration has been reduced in the roots, while its exudation to the culture
      medium has been increased. RT-PCR results indicated that the transcript levels of
      PAL, CHS, and VR genes have not been affected following Pb stress in seedlings.
      At the vegetative stage, transcript levels of PAL and CHS genes have been reduced
      in the roots. However, the transcript level of VR gene increased at 120 and 240
      MUM Pb, while it decreased at higher concentrations. In the shoot, the transcript
      levels of PAL, CHS, and VR genes were increased following increased concentration
      of lead in the medium. Overall, q-PCR results suggest that medicarpin
      biosynthesis has been induced in the shoots and reduced in the roots of the
      plants treated with a toxic concentration of Pb.

PMID- 25053288
TI  - The Bernese periacetabular osteotomy: is transection of the rectus femoris tendon
      essential?
AB  - BACKGROUND: The Bernese periacetabular osteotomy (PAO) traditionally is performed
      using the iliofemoral or the ilioinguinal approach with transection of the rectus
      femoris tendon attachments. Although a rectus-preserving approach has been
      developed, there is limited direct comparison data regarding the surgical safety,
      radiographic correction, and improvement in hip pain and function between the
      rectus-preserving and the classic approaches. QUESTIONS/PURPOSES: The purposes of
      this study were to determine whether preserving the rectus femoris tendon
      attachment would (1) reduce intraoperative blood loss and length of surgery; (2)
      improve Harris hip scores (HHS); (3) decrease the rate of complications; and (4)
      affect the radiographic correction when compared with the classic approach.
      METHODS: A retrospective matched cohort study was used to compare the endpoints
      listed above after PAO using a rectus-preserving approach versus the classic
      approach. Operative blood loss, preoperative and postoperative hematocrit,
      duration of surgery, HHS, and postoperative complications were recorded for the
      two groups. Pelvic radiographs were reviewed for measurement of the lateral
      center-edge angle, anterior center-edge angle, and Tonnis acetabular inclination
      angle. A total of 64 patients were included (32 in each group). Followup was at a
      minimum of 1 year (mean, 20 months; range, 13-44 months). RESULTS: Blood loss (p
      = 0.2405), hematocrit change (p = 0.3277), and operative time (p = 0.3960) were
      similar between groups. At latest followup, the HHS improved in the rectus
      preserving (mean improvement, 25; 95% CI, 21-29; p < 0.0001) and control groups
      (mean improvement, 21; 95% CI, 17-25; p < 0.0001) with no difference in HHS
      improvement between the groups (mean difference, 4.3; 95% CI, -1.6 to 10.1; p =
      0.1523). The complication rate was 12.5% (four of 32) in the rectus-preserving
      group and 25% (eight of 32) in the classic approach groups, respectively (p =
      0.2002). The rectus-preserving approach allowed for similar lateral center-edge
      angle (p = 0.4463), anterior center-edge angle (p = 0.0936), and Tonnis angle (p
      = 0.7953) improvement when compared with the classic approach. CONCLUSIONS: The
      rectus-preserving approach for PAO is as safe and effective as the classic
      approach to achieve radiographic correction and HHS improvement at minimum 1
      year. Additional investigation is needed to determine whether the rectus
      preserving approach allows for improvement in functional recovery including hip
      flexion strength.

PMID- 25053289
TI  - Modular tapered implants for severe femoral bone loss in THA: reliable
      osseointegration but frequent complications.
AB  - BACKGROUND: Modular tapered stems have been suggested as the optimal implants for
      patients with severe femoral bone loss (Paprosky Type IIIB and IV) undergoing
      revision total hip arthroplasty (THA); however, there are few data describing
      survivorship and hip scores associated with this treatment. QUESTIONS/PURPOSES:
      At minimum 2 years, we sought to determine the (1) survivorship of these
      implants; (2) radiographic evidence of osseointegration; and (3) the Harris hip
      scores of patients revised with a modular tapered stem for severe femoral bone
      loss including the complications associated with their use. METHODS: Between 1999
      and 2010, we performed 1124 femoral revisions; of those, 135 (12%) were performed
      using a modular tapered stem. General indications for use of this device included
      bone loss, poor quality bone, leg length discrepancy, difficulty adjusting
      version, proximal femoral remodeling, and ectatic medullary canals in the setting
      of revision THA. This report reviewed 70 of those that were performed in Type
      IIIB and IV femurs. Of those 70 patients, 11 had died and one was lost before 2
      year followup; the remaining 58 (83%, 33 with a Type IIIB femur and 25 with a
      Type IV femur) were followed for a minimum of 24 months (average, 67 months;
      range, 24-151 months). Survivorship free from revision, radiographic analysis for
      signs of subsidence or stem loosening, and Harris hip scores were tallied.
      RESULTS: One patient underwent stem revision for early subsidence followed by
      failure of ingrowth for a survivorship free from repeat revision of 98% (57 of 58
      patients). Five other stems (for a total of six [10%]) subsided early but
      nonetheless achieved radiographic signs of ingrowth and were not revised again.
      All other stems demonstrated osseointegration without subsidence and remained
      radiographically well fixed. In patients with surviving implants, the mean Harris
      hip score improved from 34 (range, 11-49) preoperatively to 74 (range, 14-100;
      p<0.001) postoperatively. Overall, 15 of 58 patients (26%) experienced a
      complication, of whom 10 (17%) underwent reoperation. CONCLUSIONS: We found that
      modular tapered stems resulted in 98% survivorship at a mean of 67 months in
      patients with Type IIIB and IV femurs undergoing femoral revision, although the
      overall complication rate in this complex subset of patients is high. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 25053291
TI  - Scandium-catalyzed tandem selective oxirane ring-opening/Friedel-Crafts
      alkylation: a facile access to [1,4]oxazino[4,3-a]indoles and 3,4-dihydro-1H
      pyrrolo[2,1-c][1,4]oxazines.
AB  - A facile technique involving a novel Lewis-acid-catalyzed tandem selective ring
      opening of oxirane and Friedel-Crafts alkylation of 1H-indol-1-yl derived
      oxiranes was developed. The developed protocol affords functionalized
      [1,4]oxazino[4,3-a]indoles and 3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazines in up
      to 95% yield. 

PMID- 25053292
TI  - Venous thromboembolism and anticoagulation safety: who is watching the children?

PMID- 25053290
TI  - Patient activity after TKA depends on patient-specific parameters.
AB  - BACKGROUND: Most patients expect an improvement of walking ability and an
      increase in activity levels after TKA. Unfortunately, few studies report
      qualitative and quantitative activity improvements after TKA. QUESTIONS/PURPOSES:
      The aims of this study were (1) to evaluate quantity and quality of physical
      activity before and after TKA with an accelerometer, and to compare activity
      level with that of an age-matched control group without lower-extremity
      disorders. (2) Improvement in measured steps per day after TKA and the ability to
      meet physical activity guidelines were evaluated. (3) The influence of patient
      specific and implant parameters were assessed. PATIENTS AND METHODS: An
      accelerometer was used to measure activity in 97 patients who were assessed
      before TKA and 1 year after TKA. The measurements included the total number of
      steps, moderate to vigorous activity defined as at least 100 steps per minute,
      and time spent lying, sitting/standing, or walking. We then calculated the
      proportion of patients who met the 10,000 steps per day guideline recommendation
      and determined factors that predicted failure to meet that goal. Thirty-nine age
      matched control subjects without lower-extremity disorders were selected and
      underwent the same assessments using the accelerometer for comparison with
      patients 1 year after TKA. RESULTS: Measured steps per day improved from a mean
      of 5278 (SD, 2999) preoperatively to 6473 (SD, 3654) postoperatively (effect
      size, 1.23; 95% CI, 1.10-1.35; p < 0.001). Moderate to vigorous steps per day
      improved from a mean of 1150 (SD, 982) to 1935 (SD, 1728; p < 0.001). Times spent
      in lying, sitting, or standing position or during walking did not change after
      TKA. For all measured parameters, activity of the patients after TKA was
      considerably less than that of the age-matched control subjects, who walked a
      mean of 13,375 (SD, 4614) steps per day (p < 0.001), performed a mean of 6562
      (SD, 3401) vigorous steps per day (p < 0.001), and spent a mean of 2.9 hours (SD,
      1.1) per day walking (p < 0.001). Only 16 patients (16.5%) met physical activity
      guidelines after TKA. BMI (p = 0.017), sex (p = 0.027), and comorbidities
      (American Society of Anesthesiologists Grade, p = 0.042) were independent factors
      associated with steps per day after TKA. CONCLUSIONS: One year after TKA,
      patients had increased walking and moderate to vigorous steps. However, only
      16.5% achieved the guideline recommendations for walking activity. BMI, sex, and
      comorbidities are patient factors that are associated with activity after TKA.
      Even with improvements in walking, activity level after TKA remains less than
      that seen for age-matched control subjects. Surgeons should be aware of this when
      counseling patients undergoing TKA. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25053294
TI  - Communication: double-hybrid functionals from adiabatic-connection: the QIDH
      model.
AB  - A new approach stemming from the adiabatic-connection (AC) formalism is proposed
      to derive parameter-free double-hybrid (DH) exchange-correlation functionals. It
      is based on a quadratic form that models the integrand of the coupling parameter,
      whose components are chosen to satisfy several well-known limiting conditions.
      Its integration leads to DHs containing a single parameter controlling the amount
      of exact exchange, which is determined by requiring it to depend on the weight of
      the MP2 correlation contribution. Two new parameter-free DHs functionals are
      derived in this way, by incorporating the non-empirical PBE and TPSS functionals
      in the underlying expression. Their extensive testing using the GMTKN30 benchmark
      indicates that they are in competition with state-of-the-art DHs, yet providing
      much better self-interaction errors and opening a new avenue towards the design
      of accurate double-hybrid exchange-correlation functionals departing from the AC
      integrand. 

PMID- 25053293
TI  - A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic
      response to sorafenib in liver tumor cells.
AB  - The multikinase inhibitor sorafenib is the only effective drug in advanced cases
      of hepatocellular carcinoma (HCC). However, response differs among patients and
      effectiveness only implies a delay. We have recently described that sorafenib
      sensitizes HCC cells to apoptosis. In this work, we have explored the response to
      this drug of six different liver tumor cell lines to define a phenotypic
      signature that may predict lack of response in HCC patients. Results have
      indicated that liver tumor cells that show a mesenchymal-like phenotype,
      resistance to the suppressor effects of transforming growth factor beta (TGF
      beta) and high expression of the stem cell marker CD44 were refractory to
      sorafenib-induced cell death in in vitro studies, which correlated with lack of
      response to sorafenib in nude mice xenograft models of human HCC. In contrast,
      epithelial-like cells expressing the stem-related proteins EpCAM or CD133 were
      sensitive to sorafenib-induced apoptosis both in vitro and in vivo. A cross-talk
      between the TGF-beta pathway and the acquisition of a mesenchymal-like phenotype
      with up-regulation of CD44 expression was found in the HCC cell lines. Targeted
      CD44 knock-down in the mesenchymal-like cells indicated that CD44 plays an active
      role in protecting HCC cells from sorafenib-induced apoptosis. However, CD44
      effect requires a TGF-beta-induced mesenchymal background, since the only
      overexpression of CD44 in epithelial-like HCC cells is not sufficient to impair
      sorafenib-induced cell death. In conclusion, a mesenchymal profile and expression
      of CD44, linked to activation of the TGF-beta pathway, may predict lack of
      response to sorafenib in HCC patients. 

PMID- 25053295
TI  - Toward transferable interatomic van der Waals interactions without electrons: the
      role of multipole electrostatics and many-body dispersion.
AB  - We estimate polarizabilities of atoms in molecules without electron density,
      using a Voronoi tesselation approach instead of conventional density partitioning
      schemes. The resulting atomic dispersion coefficients are calculated, as well as
      many-body dispersion effects on intermolecular potential energies. We also
      estimate contributions from multipole electrostatics and compare them to
      dispersion. We assess the performance of the resulting intermolecular interaction
      model from dispersion and electrostatics for more than 1300 neutral and charged,
      small organic molecular dimers. Applications to water clusters, the benzene
      crystal, the anti-cancer drug ellipticine-intercalated between two Watson-Crick
      DNA base pairs, as well as six macro-molecular host-guest complexes highlight the
      potential of this method and help to identify points of future improvement. The
      mean absolute error made by the combination of static electrostatics with many
      body dispersion reduces at larger distances, while it plateaus for two-body
      dispersion, in conflict with the common assumption that the simple 1/R(6)
      correction will yield proper dissociative tails. Overall, the method achieves an
      accuracy well within conventional molecular force fields while exhibiting a
      simple parametrization protocol. 

PMID- 25053296
TI  - Chemical potential of liquids and mixtures via adaptive resolution simulation.
AB  - We employ the adaptive resolution approach AdResS, in its recently developed
      Grand Canonical-like version (GC-AdResS) [H. Wang, C. Hartmann, C. Schutte, and
      L. Delle Site, Phys. Rev. X 3, 011018 (2013)], to calculate the excess chemical
      potential, MU(ex), of various liquids and mixtures. We compare our results with
      those obtained from full atomistic simulations using the technique of
      thermodynamic integration and show a satisfactory agreement. In GC-AdResS, the
      procedure to calculate MU(ex) corresponds to the process of standard initial
      equilibration of the system; this implies that, independently of the specific aim
      of the study, MU(ex), for each molecular species, is automatically calculated
      every time a GC-AdResS simulation is performed. 

PMID- 25053297
TI  - Practical auxiliary basis implementation of Rung 3.5 functionals.
AB  - Approximate exchange-correlation functionals for Kohn-Sham density functional
      theory often benefit from incorporating exact exchange. Exact exchange is
      constructed from the noninteracting reference system's nonlocal one-particle
      density matrix gamma(r(->), r(->)'). Rung 3.5 functionals attempt to balance the
      strengths and limitations of exact exchange using a new ingredient, a projection
      of gamma(r(->), r(->)') onto a semilocal model density matrix gamma(SL)(rho(r(
      >)), ?rho(r(->)), r(->) - r(->)'). gammaSL depends on the electron density rho(r(
      >) at reference point r(->), and is closely related to semilocal model exchange
      holes. We present a practical implementation of Rung 3.5 functionals, expanding
      the r(->) - r(->)' dependence of gammaSL in an auxiliary basis set. Energies and
      energy derivatives are obtained from 3D numerical integration as in standard
      semilocal functionals. We also present numerical tests of a range of properties,
      including molecular thermochemistry and kinetics, geometries and vibrational
      frequencies, and bandgaps and excitation energies. Rung 3.5 functionals typically
      provide accuracy intermediate between semilocal and hybrid approximations.
      Nonlocal potential contributions from gammaSL yield interesting successes and
      failures for band structures and excitation energies. The results enable and
      motivate continued exploration of Rung 3.5 functional forms.

PMID- 25053298
TI  - A perturbative formalism for electronic transitions through conical intersections
      in a fully quadratic vibronic model.
AB  - We consider a fully quadratic vibronic model Hamiltonian for studying
      photoinduced electronic transitions through conical intersections. Using a second
      order perturbative approximation for diabatic couplings, we derive an analytical
      expression for the time evolution of electronic populations at a given
      temperature. This formalism extends upon a previously developed perturbative
      technique for a linear vibronic coupling Hamiltonian. The advantage of the
      quadratic model Hamiltonian is that it allows one to use separate quadratic
      representations for potential energy surfaces of different electronic states and
      a more flexible representation of interstate couplings. We explore features
      introduced by the quadratic Hamiltonian in a series of 2D models, and then apply
      our formalism to the 2,6-bis(methylene) adamantyl cation and its dimethyl
      derivative. The Hamiltonian parameters for the molecular systems have been
      obtained from electronic structure calculations followed by a diabatization
      procedure. The evolution of electronic populations in the molecular systems using
      the perturbative formalism shows a good agreement with that from variational
      quantum dynamics. 

PMID- 25053299
TI  - A simple molecular mechanics integrator in mixed rigid body and dihedral angle
      space.
AB  - We propose a numerical scheme to integrate equations of motion in a mixed space
      of rigid-body and dihedral angle coordinates. The focus of the presentation is
      biomolecular systems and the framework is applicable to polymers with tree-like
      topology. By approximating the effective mass matrix as diagonal and lumping all
      bias torques into the time dependencies of the diagonal elements, we take
      advantage of the formal decoupling of individual equations of motion. We impose
      energy conservation independently for every degree of freedom and this is used to
      derive a numerical integration scheme. The cost of all auxiliary operations is
      linear in the number of atoms. By coupling the scheme to one of two popular
      thermostats, we extend the method to sample constant temperature ensembles. We
      demonstrate that the integrator of choice yields satisfactory stability and is
      free of mass-metric tensor artifacts, which is expected by construction of the
      algorithm. Two fundamentally different systems, viz., liquid water and an alpha
      helical peptide in a continuum solvent are used to establish the applicability of
      our method to a wide range of problems. The resultant constant temperature
      ensembles are shown to be thermodynamically accurate. The latter relies on
      detailed, quantitative comparisons to data from reference sampling schemes
      operating on exactly the same sets of degrees of freedom. 

PMID- 25053300
TI  - Water interactions with hydrophobic groups: assessment and recalibration of
      semiempirical molecular orbital methods.
AB  - In this work, we present a study of the ability of different semiempirical
      methods to describe intermolecular interactions in water solution. In particular,
      we focus on methods based on the Neglect of Diatomic Differential Overlap
      approximation. Significant improvements of these methods have been reported in
      the literature in the past years regarding the description of non-covalent
      interactions. In particular, a broad range of methodologies has been developed to
      deal with the properties of hydrogen-bonded systems, with varying degrees of
      success. In contrast, the interactions between water and a molecule containing
      hydrophobic groups have been little analyzed. Indeed, by considering the
      potential energy surfaces obtained using different semiempirical Hamiltonians for
      the intermolecular interactions of model systems, we found that none of the
      available methods provides an entirely satisfactory description of both
      hydrophobic and hydrophilic interactions in water. In addition, a vibrational
      analysis carried out in a model system for these interactions, a methane
      clathrate cluster, showed that some recent methods cannot be used to carry out
      studies of vibrational properties. Following a procedure established in our group
      [M. I. Bernal-Uruchurtu, M. T. C. Martins-Costa, C. Millot, and M. F. Ruiz-Lopez,
      J. Comput. Chem. 21, 572 (2000); W. Harb, M. I. Bernal-Uruchurtu, and M. F. Ruiz
      Lopez, Theor. Chem. Acc. 112, 204 (2004)], we developed new parameters for the
      core-core interaction terms based on fitting potential energy curves obtained at
      the MP2 level for our model system. We investigated the transferability of the
      new parameters to describe a system, having both hydrophilic and hydrophobic
      groups, interacting with water. We found that only by introducing two different
      sets of parameters for hydrophilic and hydrophobic hydrogen atom types we are
      able to match the features of the ab initio calculated properties. Once this
      assumption is made, a good agreement with the MP2 reference is achieved. The
      results reported in this work provide therefore a direction for future
      developments of semiempirical approaches that are still required to investigate
      chemical processes in biomolecules and in large disordered systems. 

PMID- 25053302
TI  - Spin projection with double hybrid density functional theory.
AB  - A spin projected double-hybrid density functional theory is presented that
      accounts for different scaling of opposite and same spin terms in the second
      order correction. This method is applied to three dissociation reactions which in
      the unprojected formalism exhibit significant spin contamination with higher spin
      states. This gives rise to a distorted potential surface and can lead to poor
      geometries and energies. The projected method presented is shown to improve the
      description of the potential over unprojected double hybrid density functional
      theory. Comparison is made with the reference states of the two double hybrid
      functionals considered here (B2PLYP and mPW2PLYP) in which the projected
      potential surface is degraded by an imbalance in the description of dynamic and
      static correlation. 

PMID- 25053301
TI  - Accurate molecular structures and infrared spectra of trans-2,3-dideuterooxirane,
      methyloxirane, and trans-2,3-dimethyloxirane.
AB  - Oxirane derivatives are the most used benchmarks for chiroptical spectroscopies
      in view of their small size and relative rigidity. The molecular structure,
      vibrational harmonic and anharmonic frequencies, and infrared intensities of the
      ground electronic states are analyzed in this paper. Equilibrium structure and
      harmonic force fields have been evaluated by means of high-level quantum-chemical
      calculations at the coupled-cluster level including single and double excitations
      together with a perturbative treatment of triples (CCSD(T)). Extrapolation to the
      complete basis-set limit as well as core-correlation effects have also been taken
      into account. Anharmonic contributions have been computed at the CCSD(T)/cc-pVTZ
      level for trans-2,3-dideuterooxirane. These data can serve as references to
      evaluate the accuracy of less expensive computational approaches rooted in the
      density functional theory (DFT). The latter have been used within hybrid CC/DFT
      approaches, which have been applied to simulate fully anharmonic infrared (IR)
      spectra. Finally, the best theoretical estimates of the equilibrium structures
      and vibrational wavenumbers are compared to the most accurate experimental data
      and show in all cases very good agreement, i.e., within 0.001 A, 0.1 deg, 10 cm(
      1), and 0.5 km mol(-1), for bond lengths, angles, wavenumbers, and IR
      intensities, respectively. 

PMID- 25053304
TI  - Rapid calculation method for Frenkel-type two-exciton states in one to three
      dimensions.
AB  - Biexciton and two-exciton dissociated states of Frenkel-type excitons are well
      described by a tight-binding model with a nearest-neighbor approximation. Such
      two-exciton states in a finite-size lattice are usually calculated by numerical
      diagonalization of the Hamiltonian, which requires an increasing amount of
      computational time and memory as the lattice size increases. I develop here a
      rapid, memory-saving method to calculate the energies and wave functions of two
      exciton states by employing a bisection method. In addition, an attractive
      interaction between two excitons in the tight-binding model can be obtained
      directly so that the biexciton energy agrees with the observed energy, without
      the need for the trial-and-error procedure implemented in the numerical
      diagonalization method. 

PMID- 25053303
TI  - Permutation invariant polynomial neural network approach to fitting potential
      energy surfaces. III. Molecule-surface interactions.
AB  - The permutation invariant polynomial-neural network (PIP-NN) method for
      constructing highly accurate potential energy surfaces (PESs) for gas phase
      molecules is extended to molecule-surface interaction PESs. The symmetry
      adaptation in the NN fitting of a PES is achieved by employing as the input
      symmetry functions that fulfill both the translational symmetry of the surface
      and permutation symmetry of the molecule. These symmetry functions are low-order
      PIPs of the primitive symmetry functions containing the surface periodic
      symmetry. It is stressed that permutationally invariant cross terms are needed to
      avoid oversymmetrization. The accuracy and efficiency are demonstrated in fitting
      both a model PES for the H2 + Cu(111) system and density functional theory points
      for the H2 + Ag(111) system. 

PMID- 25053305
TI  - Nonstatistical dynamics on the caldera.
AB  - We explore both classical and quantum dynamics of a model potential exhibiting a
      caldera: that is, a shallow potential well with two pairs of symmetry related
      index one saddles associated with entrance/exit channels. Classical trajectory
      simulations at several different energies confirm the existence of the "dynamical
      matching" phenomenon originally proposed by Carpenter, where the momentum
      direction associated with an incoming trajectory initiated at a high energy
      saddle point determines to a considerable extent the outcome of the reaction
      (passage through the diametrically opposing exit channel). By studying a
      "stretched" version of the caldera model, we have uncovered a generalized
      dynamical matching: bundles of trajectories can reflect off a hard potential wall
      so as to end up exiting predominantly through the transition state opposite the
      reflection point. We also investigate the effects of dissipation on the classical
      dynamics. In addition to classical trajectory studies, we examine the dynamics of
      quantum wave packets on the caldera potential (stretched and unstretched). These
      computations reveal a quantum mechanical analogue of the "dynamical matching"
      phenomenon, where the initial expectation value of the momentum direction for the
      wave packet determines the exit channel through which most of the probability
      density passes to product. 

PMID- 25053306
TI  - A direct method to transform between expansions in the configuration state
      function and Slater determinant bases.
AB  - A novel algorithm is introduced for the transformation of wave functions between
      the bases of Slater determinants (SD) and configuration state functions (CSF) in
      the genealogical coupling scheme. By modifying the expansion coefficients as each
      electron is spin-coupled, rather than performing a single many-electron
      transformation, the large transformation matrix that plagues previous approaches
      is avoided and the required number of operations is drastically reduced. As an
      example of the efficiency of the algorithm, the transformation for a
      configuration with 30 unpaired electrons and singlet spin is discussed. For this
      case, the 10 * 10(6) coefficients in the CSF basis is obtained from the 150 *
      10(6) coefficients in the SD basis in 1 min, which should be compared with the
      seven years that the previously employed method is estimated to require. 

PMID- 25053307
TI  - Variational mixed quantum/semiclassical simulation of dihalogen guest and rare
      gas solid host dynamics.
AB  - A variational mixed quantum-semiclassical theory for the internal nuclear
      dynamics of a small molecule and the induced small-amplitude coherent motion of a
      low-temperature host medium is developed, tested, and used to simulate the
      temporal evolution of nonstationary states of the internal molecular and
      surrounding medium degrees of freedom. In this theory, termed the Fixed
      Vibrational Basis/Gaussian Bath (FVB/GB) method, the system is treated fully
      quantum mechanically while Gaussian wave packets are used for the bath degrees of
      freedom. An approximate time-dependent wave function of the entire model is
      obtained instead of just a reduced system density matrix, so the theory enables
      the analysis of the entangled system and bath dynamics that ensues following
      initial displacement of the internal-molecular (system) coordinate from its
      equilibrium position. The norm- and energy-conserving properties of the
      propagation of our trial wave function are natural consequences of the Dirac
      Frenkel-McLachlan variational principle. The variational approach also stabilizes
      the time evolution in comparison to the same ansatz propagated under a previously
      employed locally quadratic approximation to the bath potential and system-bath
      interaction terms in the bath-parameter equations of motion. Dynamics
      calculations are carried out for molecular iodine in a 2D krypton lattice that
      reveal both the time-course of vibrational decoherence and the details of host
      atom motion accompanying energy dissipation and dephasing. This work sets the
      stage for the comprehensive simulation of ultrafast time-resolved optical
      experiments on small molecules in low-temperature solids. 

PMID- 25053308
TI  - Extending the applicability of the Tkatchenko-Scheffler dispersion correction via
      iterative Hirshfeld partitioning.
AB  - Recently we have demonstrated that the applicability of the Tkatchenko-Scheffler
      (TS) method for calculating dispersion corrections to density-functional theory
      can be extended to ionic systems if the Hirshfeld method for estimating effective
      volumes and charges of atoms in molecules or solids (AIM's) is replaced by its
      iterative variant [T. Bucko, S. Lebegue, J. Hafner, and J. Angyan, J. Chem.
      Theory Comput. 9, 4293 (2013)]. The standard Hirshfeld method uses neutral atoms
      as a reference, whereas in the iterative Hirshfeld (HI) scheme the fractionally
      charged atomic reference states are determined self-consistently. We show that
      the HI method predicts more realistic AIM charges and that the TS/HI approach
      leads to polarizabilities and C6 dispersion coefficients in ionic or partially
      ionic systems which are, as expected, larger for anions than for cations (in
      contrast to the conventional TS method). For crystalline materials, the new
      algorithm predicts polarizabilities per unit cell in better agreement with the
      values derived from the Clausius-Mosotti equation. The applicability of the TS/HI
      method has been tested for a wide variety of molecular and solid-state systems.
      It is demonstrated that for systems dominated by covalent interactions and/or
      dispersion forces the TS/HI method leads to the same results as the conventional
      TS approach. The difference between the TS/HI and TS approaches increases with
      increasing ionicity. A detailed comparison is presented for isoelectronic series
      of octet compounds, layered crystals, complex intermetallic compounds, and
      hydrides, and for crystals built of molecules or containing molecular anions. It
      is demonstrated that only the TS/HI method leads to accurate results for systems
      where both electrostatic and dispersion interactions are important, as
      illustrated for Li-intercalated graphite and for molecular adsorption on the
      surfaces in ionic solids and in the cavities of zeolites. 

PMID- 25053309
TI  - Perturbative many-body expansion for electrostatic energy and field for system of
      polarizable charged spherical ions in a dielectric medium.
AB  - An analytical solution for the electrostatic energy and potential for a system of
      charged, polarizable spheres in a dielectric medium is developed from a multiple
      scattering expansion that is equivalent to a formal solution to Poisson's
      equation for the system. The leading contributions emerge in the form of
      effective two-, three-, and four-body interactions that are explicit analytical
      functions of the sphere positions, charges, and internal dielectric constants and
      the external dielectric constant, thereby also enabling analytical computation of
      the electrostatic forces on the ions. Tests of successive terms demonstrate their
      rapid convergence. Similar methods can be used to evaluate higher order
      contributions and the expansion for the electrostatic field. The results will
      prove far more efficient for MD and MC simulations with spherical particles than
      current approximate methods that require the computation of surface polarization
      charge distributions but that apply also for systems with complex geometries. 

PMID- 25053310
TI  - Calculation of the vibrational excited states of malonaldehyde and their
      tunneling splittings with the multi-configuration time-dependent Hartree method.
AB  - We report energies and tunneling splittings of vibrational excited states of
      malonaldehyde which have been obtained using full dimensional quantum mechanical
      calculations. To this end we employed the multi configuration time-dependent
      Hartree method. The results have been obtained using a recently published
      potential energy surface [Y. Wang, B. J. Braams, J. M. Bowman, S. Carter, and D.
      P. Tew, J. Chem. Phys. 128, 224314 (2008)] which has been brought into a suitable
      form by a modified version of the n-mode representation which was used with two
      different arrangements of coordinates. The relevant terms of the expansion have
      been identified with a Metropolis algorithm and a diffusion Monte-Carlo
      technique, respectively. 

PMID- 25053311
TI  - Analytical approach for collective diffusion: one-dimensional homogeneous
      lattice.
AB  - Diffusion of particles adsorbed on the homogeneous one-dimensional chain was
      investigated using a theoretical approach and kinetic Monte Carlo simulations.
      The concentration dependencies of the center-of-mass and Fickian diffusion
      coefficients have been calculated for some representative values of lateral
      interactions between adsorbed particles. The analytical dependencies have been
      compared with the numerical data. The perfect coincidence of the data obtained by
      the two quite different methods clearly demonstrates that the analytical
      expressions for the diffusion coefficients derived in the framework of the
      approach based on the non-equilibrium statistical operator exactly describe the
      particle migration in the lattice gas systems. 

PMID- 25053312
TI  - A novel method for calculating the energy barriers for carbon diffusion in
      ferrite under heterogeneous stress.
AB  - A novel method for accurate and efficient evaluation of the change in energy
      barriers for carbon diffusion in ferrite under heterogeneous stress is
      introduced. This method, called Linear Combination of Stress States, is based on
      the knowledge of the effects of simple stresses (uniaxial or shear) on these
      diffusion barriers. Then, it is assumed that the change in energy barriers under
      a complex stress can be expressed as a linear combination of these already known
      simple stress effects. The modifications of energy barriers by either uniaxial
      traction/compression and shear stress are determined by means of atomistic
      simulations with the Climbing Image-Nudge Elastic Band method and are stored as a
      set of functions. The results of this method are compared to the predictions of
      anisotropic elasticity theory. It is shown that, linear anisotropic elasticity
      fails to predict the correct energy barrier variation with stress (especially
      with shear stress) whereas the proposed method provides correct energy barrier
      variation for stresses up to ~3 GPa. This study provides a basis for the
      development of multiscale models of diffusion under non-uniform stress. 

PMID- 25053313
TI  - Neutron diffraction studies for realtime leaching of catalytic Ni.
AB  - The leaching of Al from intermetallic samples of Nickel Aluminium alloys to form
      Raney-type nickel catalysts is widely used in the hydrogenation industry,
      however, little is known of the leaching process itself. In this study, the
      leaching of Al was measured in realtime, in situ, using the high-flux powder
      neutron diffractometer, D20, at the Institut Laue-Langevin. Despite the
      liberation of hydrogen and effervescent nature of the reaction the transformation
      of the dry powder phases into Raney-type Ni was determined. Samples produced by
      gas-atomisation were found to leach faster than those produced using the cast and
      crushed technique. Regardless of processing route of the precursor powder, the
      formation of spongy-Ni occurs almost immediately, while Ni2Al3 and NiAl3 continue
      to transform over longer periods of time. Small-angle scattering and broadening
      of the diffraction peaks is an evidence for the formation of the smaller Ni
      particles. Understanding the kinetics of the leaching process will allow industry
      to refine production of catalysts for optimum manufacturing time while knowledge
      of leaching dynamics of powders produced by different manufacturing techniques
      will allow further tailoring of catalytic materials. 

PMID- 25053314
TI  - Potential of ZrO clusters as replacement Pd catalyst.
AB  - Atomic clusters with specific size and composition and mimicking the chemistry of
      elements in the periodic table are commonly known as superatoms. It has been
      suggested that superatoms could be used to replace elements that are either
      scarce or expensive. Based on a photoelectron spectroscopy experiment of
      negatively charged ions, Castleman and co-workers [Proc. Natl. Acad. Sci. U.S.A.
      107, 975 (2010)] have recently shown that atoms of Ni, Pd, and Pt which are well
      known for their catalytic properties, have the same electronic structure as their
      counterpart isovalent diatomic species, TiO, ZrO, and WC, respectively. Based on
      this similarity they have suggested that ZrO, for example, could be a replacement
      catalyst for Pd. Since catalysts are seldom single isolated atoms, one has to
      demonstrate that clusters of ZrO also have the same electronic structure as same
      sized Pd clusters. To examine if this is indeed the case, we have calculated the
      geometries, electronic structure, electron affinity, ionization potential, and
      hardness of Pdn and (ZrO)n clusters (n = 1-5). We further studied the reaction of
      these clusters in neutral and charged forms with H2, O2, and CO and found it to
      be qualitatively different in most cases. These results obtained using density
      functional theory with hybrid B3LYP functional do not support the view that ZrO
      clusters can replace Pd as a catalyst. 

PMID- 25053315
TI  - Accurate calculations of bound rovibrational states for argon trimer.
AB  - This work presents a comprehensive quantum dynamics calculation of the bound
      rovibrational eigenstates of argon trimer (Ar3), using the ScalIT suite of
      parallel codes. The Ar3 rovibrational energy levels are computed to a very high
      level of accuracy (10(-3) cm(-1) or better), and up to the highest rotational and
      vibrational excitations for which bound states exist. For many of these
      rovibrational states, wavefunctions are also computed. Rare gas clusters such as
      Ar3 are interesting because the interatomic interactions manifest through long
      range van der Waals forces, rather than through covalent chemical bonding. As a
      consequence, they exhibit strong Coriolis coupling between the rotational and
      vibrational degrees of freedom, as well as highly delocalized states, all of
      which renders accurate quantum dynamical calculation difficult. Moreover, with
      its (comparatively) deep potential well and heavy masses, Ar3 is an especially
      challenging rare gas trimer case. There are a great many rovibrational
      eigenstates to compute, and a very high density of states. Consequently, very few
      previous rovibrational state calculations for Ar3 may be found in the current
      literature-and only for the lowest-lying rotational excitations. 

PMID- 25053316
TI  - A photoelectron spectroscopy and ab initio study of the structures and chemical
      bonding of the B25(-) cluster.
AB  - Photoelectron spectroscopy and ab initio calculations are used to investigate the
      structures and chemical bonding of the B25(-) cluster. Global minimum searches
      reveal a dense potential energy landscape with 13 quasi-planar structures within
      10 kcal/mol at the CCSD(T)/6-311+G(d) level of theory. Three quasi-planar isomers
      (I, II, and III) are lowest in energy and nearly degenerate at the CCSD(T) level
      of theory, with II and III being 0.8 and 0.9 kcal/mol higher, respectively,
      whereas at two density functional levels of theory isomer III is the lowest in
      energy (8.4 kcal/mol more stable than I at PBE0/6-311+G(2df) level). Comparison
      with experimental photoelectron spectroscopic data shows isomer II to be the
      major contributor while isomers I and III cannot be ruled out as minor
      contributors to the observed spectrum. Theoretical analyses reveal similar
      chemical bonding in I and II, both involving peripheral 2c-2e B-B sigma-bonding
      and delocalized interior sigma- and pi-bonding. Isomer III has an interesting
      elongated ribbon-like structure with a pi-bonding pattern analogous to those of
      dibenzopentalene. The high density of low-lying isomers indicates the complexity
      of the medium-sized boron clusters; the method dependency of predicting relative
      energies of the low-lying structures for B25(-) suggests the importance of
      comparison with experiment in determining the global minima of boron clusters at
      this size range. The appearance of many low-lying quasi-planar structures
      containing a hexagonal hole in B25(-) suggests the importance of this structural
      feature in maintaining planarity of larger boron clusters.

PMID- 25053317
TI  - The broadband microwave spectra of the monoterpenoids thymol and carvacrol:
      conformational landscape and internal dynamics.
AB  - The rotational spectra of the monoterpenoids thymol and carvacrol are reported in
      the frequency range 2-8.5 GHz, obtained with broadband Fourier-transform
      microwave spectroscopy. For carvacrol four different conformations were
      identified in the cold conditions of the molecular jet, whereas only three
      conformations were observed for thymol. The rotational constants and other
      molecular parameters are reported and compared with quantum chemical
      calculations. For both molecules, line splittings due to methyl group internal
      rotation were observed and the resulting barrier heights could be determined. The
      experimental barrier heights, 4.0863(25) kJ/mol for trans-carvacrol-A, 4.4024(16)
      kJ/mol for trans-carvacrol-B, and 0.3699(11) kJ/mol for trans-thymol-A, are
      compared with similar molecules. 

PMID- 25053318
TI  - Ab initio ro-vibronic spectroscopy of SiCCl (X(2)Pi).
AB  - The full dimensional potential energy surfaces of the (2)A' and (2)A'' electronic
      components of X(2)Pi SiCCl have been computed using the explicitly correlated
      coupled cluster method, UCCSD(T)-F12b, combined with a composite approach taking
      into account basis set incompleteness, core-valence correlation, scalar
      relativity, and higher order excitations. The spin-orbit and dipole moment
      surfaces have also been computed ab initio. The ro-vibronic energy levels and
      absorption spectrum at 5 K have been determined from variational calculations.
      The influence of each correction on the fundamental frequencies is discussed. An
      assignment is proposed for bands observed in the LIF experiment of Smith et al.
      [J. Chem. Phys. 117, 6446 (2002)]. The overall agreement between the experimental
      and calculated ro-vibronic levels is better than 7 cm(-1) which is comparable
      with the 10-20 cm(-1) resolution of the emission spectrum.

PMID- 25053319
TI  - Low energy positron interactions with uracil--total scattering, positronium
      formation, and differential elastic scattering cross sections.
AB  - Measurements of the grand total and total positronium formation cross sections
      for positron scattering from uracil have been performed for energies between 1
      and 180 eV, using a trap-based beam apparatus. Angular, quasi-elastic
      differential cross section measurements at 1, 3, 5, 10, and 20 eV are also
      presented and discussed. These measurements are compared to existing experimental
      results and theoretical calculations, including our own calculations using a
      variant of the independent atom approach. 

PMID- 25053320
TI  - The ionization potential of aqueous hydroxide computed using many-body
      perturbation theory.
AB  - The ionization potentials of electrolyte solutions provide important information
      about the electronic structure of liquids and solute-solvent interactions. We
      analyzed the positions of solute and solvent bands of aqueous hydroxide and the
      influence of the solvent environment on the ionization potential of hydroxide
      ions. We used the concept of a computational hydrogen electrode to define
      absolute band positions with respect to vacuum. We found that many-body
      perturbation theory in the G0 W0 approximation substantially improves the
      relative and absolute positions of the band edges of solute and solvent with
      respect to those obtained within Density Functional Theory, using semi-local
      functionals, yielding results in satisfactory agreement with recent experiments. 

PMID- 25053321
TI  - Direct observation of intermolecular interactions mediated by hydrogen bonding.
AB  - Although intermolecular interactions are ubiquitous in physicochemical phenomena,
      their dynamics have proven difficult to observe directly, and most experiments
      rely on indirect measurements. Using broadband two-dimensional infrared
      spectroscopy (2DIR), we have measured the influence of hydrogen bonding on the
      intermolecular vibrational coupling between dimerized N-methylacetamide
      molecules. In addition to strong intramolecular coupling between N-H and C=O
      oscillators, cross-peaks in the broadband 2DIR spectrum appearing upon
      dimerization reveal strong intermolecular coupling that changes the character of
      the vibrations. In addition, dimerization changes the effects of intramolecular
      coupling, resulting in Fermi resonances between high and low-frequency modes.
      These results illustrate how hydrogen bonding influences the interplay of inter-
      and intramolecular vibrations, giving rise to correlated nuclear motions and
      significant changes in the vibrational structure of the amide group. These
      observations have direct impact on modeling and interpreting the IR spectra of
      proteins. In addition, they illustrate a general approach to direct molecular
      characterization of intermolecular interactions. 

PMID- 25053322
TI  - Can xenon in water inhibit ice growth? Molecular dynamics of phase transitions in
      water-Xe system.
AB  - Motivated by recent experiments showing the promise of noble gases as
      cryoprotectants, we perform molecular dynamics modeling of phase transitions in
      water with xenon under cooling. We follow the structure and dynamics of xenon
      water solution as a function of temperature. Homogeneous nucleation of clathrate
      hydrate phase is observed and characterized. As the temperature is further
      reduced we observe hints of dissociation of clathrate due to stronger hydrophobic
      hydration, pointing towards a possible instability of clathrate at cryogenic
      temperatures and conversion to an amorphous phase comprised of "xenon + hydration
      shell" Xe.(H2O)21.5 clusters. Simulations of ice-xenon solution interface in
      equilibrium and during ice growth reveal the effects of xenon on the ice-liquid
      interface, where adsorbed xenon causes roughening of ice surface but does not
      preferentially form clathrate. These results provide evidence against the ice
      blocker mechanism of xenon cryoprotection. 

PMID- 25053323
TI  - One- and two-photon absorption in solution: the effects of a passive auxiliary
      beam.
AB  - The efficiencies of one- and two-photon absorption by chromophores in solution
      may be significantly modified by a sufficiently intense beam of off-resonant
      light. A molecular analysis based on quantum electrodynamics (QED) fully accounts
      for this phenomenon of laser-modified absorption. A time-dependent perturbation
      theory treatment describes the process in terms of stimulated forward Rayleigh
      scattering of the auxiliary beam occurring simultaneously with the absorption
      interaction(s). Our formulation accommodates media modifications to the basic
      character of light-matter interactions, taking into account the refractive and
      dispersive properties of a solution-phase environment. This introduces the bulk
      refractive index of the solvent directly into the QED framework. The measurable
      electronic response of molecules freely rotating in solution is defined by an
      average of all orientations. We explicitly derive fixed-orientation and
      rotationally averaged calculations for the Fermi-rule rate of laser-modified one-
      and two-photon absorption. For a given beam polarization geometry, the solution
      phase molecular response is expressible as a set of natural invariant scalars.
      These results reveal details of the dependence on the beam polarisations and on
      the rotationally averaged molecular response: we illustrate the breadth of
      variation available via geometric manipulation of beam polarization, and raise
      new possibilities for quantum weak measurements of laser states. 

PMID- 25053324
TI  - Glass transition and relaxation dynamics of propylene glycol-water solutions
      confined in clay.
AB  - The molecular dynamics of aqueous solutions of propylene glycol (PG) and
      propylene glycol methylether (PGME) confined in a two-dimensional layer
      structured Na-vermiculite clay has been studied by broadband dielectric
      spectroscopy and differential scanning calorimetry. As typical for liquids in
      confined geometries the intensity of the cooperative alpha-relaxation becomes
      considerably more suppressed than the more local beta-like relaxation processes.
      In fact, at high water contents the calorimetric glass transition and related
      structural alpha-relaxation cannot even be observed, due to the confinement.
      Thus, the intensity of the viscosity related alpha-relaxation is dramatically
      reduced, but its time scale as well as the related glass transition temperature
      Tg are for both systems only weakly influenced by the confinement. In the case of
      the PGME-water solutions it is an important finding since in the corresponding
      bulk system a pronounced non-monotonic concentration dependence of the glass
      transition related dynamics has been observed due to the growth of hydrogen
      bonded relaxing entities of water bridging between PGME molecules [J. Sjostrom,
      J. Mattsson, R. Bergman, and J. Swenson, Phys. Chem. B 115, 10013 (2011)]. The
      present results suggest that the same type of structural entities are formed in
      the quasi-two-dimensional space between the clay platelets. It is also observed
      that the main water relaxation cannot be distinguished from the beta-relaxation
      of PG or PGME in the concentration range up to intermediate water contents. This
      suggests that these two processes are coupled and that the water molecules affect
      the time scale of the beta-relaxation. However, this is most likely true also for
      the corresponding bulk solutions, which exhibit similar time scales of this
      combined relaxation process below Tg. Finally, it is found that at higher water
      contents the water relaxation does not merge with, or follow, the alpha
      relaxation above Tg, but instead crosses the alpha-relaxation, indicating that
      the two relaxation processes are independent of each other. This can only occur
      if the two processes do not occur in the same parts of the confined solutions.
      Most likely the hydration shell of the interlayer Na(+) ions is causing this
      water relaxation, which does not participate in the alpha-relaxation at any
      temperature. 

PMID- 25053325
TI  - Ultrafast vibrational dynamics of BH4(-) ions in liquid and crystalline
      environments.
AB  - Ultrafast vibrational dynamics of BH4(-) ions, the key units in boron hydride
      materials for hydrogen storage, are studied in diluted polar liquid solution and
      in NaBH4 crystallites by femtosecond infrared spectroscopy. Two-color pump-probe
      experiments reveal v = 1 lifetimes of 3 ps for the asymmetric BH4(-) stretching
      mode nu3 and of 3.6 ps for the asymmetric bending mode nu4 in the solvent
      isopropylamine. We provide direct evidence for the BH4(-) stretching relaxation
      pathway via the asymmetric bending mode nu4 by probing the latter after
      femtosecond excitation of nu3. Pump-probe traces measured in the crystalline
      phase show signatures of radiative coupling between the densely packed BH4(-)
      oscillators, most clearly manifested in an accelerated subpicosecond depopulation
      of the v = 1 state of the nu4 mode. The radiative decay is followed by incoherent
      vibrational relaxation similar to the liquid phase. The excess energy released in
      the relaxation processes of the BH4(-) intramolecular modes is transferred into
      the environment with thermal pump-probe signals being much more pronounced in the
      dense solid than in the diluted solution.

PMID- 25053326
TI  - Comparison of x-ray absorption spectra between water and ice: new ice data with
      low pre-edge absorption cross-section.
AB  - The effect of crystal growth conditions on the O K-edge x-ray absorption spectra
      of ice is investigated through detailed analysis of the spectral features. The
      amount of ice defects is found to be minimized on hydrophobic surfaces, such as
      BaF2(111), with low concentration of nucleation centers. This is manifested
      through a reduction of the absorption cross-section at 535 eV, which is
      associated with distorted hydrogen bonds. Furthermore, a connection is made
      between the observed increase in spectral intensity between 544 and 548 eV and
      high-symmetry points in the electronic band structure, suggesting a more extended
      hydrogen-bond network as compared to ices prepared differently. The spectral
      differences for various ice preparations are compared to the temperature
      dependence of spectra of liquid water upon supercooling. A double-peak feature in
      the absorption cross-section between 540 and 543 eV is identified as a
      characteristic of the crystalline phase. The connection to the interpretation of
      the liquid phase O K-edge x-ray absorption spectrum is extensively discussed. 

PMID- 25053327
TI  - How to quantify structural anomalies in fluids?
AB  - Some fluids are known to behave anomalously. The so-called structural anomaly
      which means that the fluid becomes less structures under isothermal compression
      is among the most frequently discussed ones. Several methods for quantifying the
      degree of structural order are described in the literature and are used for
      calculating the region of structural anomaly. It is generally thought that all of
      the structural order determinations yield qualitatively identical results.
      However, no explicit comparison was made. This paper presents such a comparison
      for the first time. The results of some definitions are shown to contradict the
      intuitive notion of a fluid. On the basis of this comparison, we show that the
      region of structural anomaly can be most reliably determined from the behavior of
      the excess entropy. 

PMID- 25053328
TI  - Computer simulation study of surface wave dynamics at the crystal-melt interface.
AB  - We study, by means of computer simulations, the crystal-melt interface of three
      different systems: hard-spheres, Lennard Jones, and the TIP4P/2005 water model.
      In particular, we focus on the dynamics of surface waves. We observe that the
      processes involved in the relaxation of surface waves are characterized by
      distinct time scales: a slow one related to the continuous recrystallization and
      melting, that is governed by capillary forces; and a fast one which we suggest to
      be due to a combination of processes that quickly cause small perturbations to
      the shape of the interface (e.g., Rayleigh waves, subdiffusion, or
      attachment/detachment of particles to/from the crystal). The relaxation of
      surface waves becomes dominated by the slow process as the wavelength increases.
      Moreover, we see that the slow relaxation is not influenced by the details of the
      microscopic dynamics. In a time scale characteristic for the diffusion of the
      liquid phase, the relaxation dynamics of the crystal-melt interface of water is
      around one order of magnitude slower than that of Lennard Jones or hard spheres,
      which we ascribe to the presence of orientational degrees of freedom in the water
      molecule. Finally, we estimate the rate of crystal growth from our analysis of
      the capillary wave dynamics and compare it with previous simulation studies and
      with experiments for the case of water. 

PMID- 25053329
TI  - Dissociative adsorption of CO2 on flat, stepped, and kinked Cu surfaces.
AB  - We studied the dissociative adsorption of CO2 to CO + O on the Cu(111), Cu(221),
      Cu(211), and Cu(11 5 9) surfaces by using state-of-the-art density functional
      theory (DFT) within a generalized gradient approximation (GGA) and van der Waals
      density functional (vdW-DF) calculations. The activation energy for CO2
      dissociation on the flat Cu(111) surface is 1.33 eV. The activation energies on
      stepped and kinked surfaces are 1.06 eV, 0.67 eV, and 1.02 eV for the Cu(221),
      Cu(211), and Cu(11 5 9) surfaces, respectively. Even though the activation energy
      is 0.66 eV lower on the stepped Cu(211) surface than on the flat Cu(111) surface,
      we conclude that CO2 does not dissociate on "ideal" flat, stepped, or kinked Cu
      surfaces at low temperature. We attribute the discrepancy between our theoretical
      results and experimentally observed CO2 dissociation on stepped Cu surfaces below
      150 K to other factors such as effects of Cu adatoms, gas phase or condensed CO2
      molecules, or interaction with other gas phase molecules. 

PMID- 25053330
TI  - Magnetic moment enhancement and spin polarization switch of the manganese
      phthalocyanine molecule on an IrMn(100) surface.
AB  - The geometric, electronic, and magnetic structures of a manganese phthalocyanine
      (MnPc) molecule on an antiferromagnetic IrMn(100) surface are studied by density
      functional theory calculations. Two kinds of orientation of the adsorbed MnPc
      molecule are predicted to coexist due to molecular self-assembly on the surface-a
      top-site geometry with the Mn-N bonds aligned along the ?100? direction, and a
      hollow-site orientation in which the Mn-N bonds are parallel to the ?110?
      direction. The MnPc molecule is antiferromagnetically coupled to the substrate at
      the top site with a slight reduction in the magnetic moment of the Mn atom of the
      MnPc molecule (Mnmol). In contrast, the magnetic moment of the Mnmol is enhanced
      to 4.28 MUB at the hollow site, a value larger than that in the free MnPc
      molecule (3.51 MUB). Molecular distortion induced by adsorption is revealed to be
      responsible for the enhancement of the magnetic moment. Furthermore, the spin
      polarization of the Mnmol atom at around the Fermi level is found to change from
      negative to positive through an elongation of the Mn-N bonds of the MnPc. We
      propose that a reversible switch of the low/high magnetic moment and
      negative/positive spin polarization might be realized through some mechanical
      engineering methods. 

PMID- 25053331
TI  - Electron-phonon couplings and carrier mobility in graphynes sheet calculated
      using the Wannier-interpolation approach.
AB  - Electron-phonon couplings and charge transport properties of alpha- and gamma
      graphyne nanosheets were investigated from first-principles calculations by using
      the density-functional perturbation theory and the Boltzmann transport equation.
      Wannier function-based interpolation techniques were applied to obtain the ultra
      dense electron-phonon coupling matrix elements. Due to the localization feature
      in Wannier space, the interpolation based on truncated space is found to be
      accurate. We demonstrated that the intrinsic electron-phonon scatterings in these
      two-dimensional carbon materials are dominated by low-energy longitudinal
      acoustic phonon scatterings over a wide range of temperatures. In contrast, the
      high-frequency optical phonons play appreciable roles only at high temperature
      regimes. The electron mobilities of alpha- and gamma-graphynes are predicted to
      be ~10(4) cm(2) V(-1) s(-1) at room temperature. 

PMID- 25053332
TI  - The solvent-induced interaction of spherical solutes in associated and non
      associated liquids.
AB  - We propose an efficient method for studying the solvent-induced interaction of
      two solvophobic particles immersed in a liquid solvent. The method is based on
      the combination of the probabilistic hydrogen bond model with the density
      functional theory. An analytic expression for the number of hydrogen bonds per
      water molecule near two spherical hydrophobes is derived as a function of the
      molecule distance to both hydrophobes, distance between hydrophobes, and their
      radii. Using this expression, one can construct an approximation for the
      distribution of fluid (liquid water) molecules in the system which provides a
      reasonably good (much faster and accurate enough) alternative to a standard
      iteration procedure. Such an approximate density distribution constitutes an
      efficient foundation for studying the length-scale and temperature dependence of
      hydrophobic interactions. The model is applied to the interaction of solvophobic
      solutes in both associated and non-associated liquids. Of these two cases, the
      model predictions for the solvent-induced potential of mean force between two
      solutes in associated liquids are closer to the results of molecular dynamics
      simulation of hydrophobic interactions in the SPC/E model water. Our results
      suggest that the hydrogen bonding ability of water molecules may play a major
      role in hydrophobic phenomena. 

PMID- 25053333
TI  - Effects of non-local exchange on core level shifts for gas-phase and adsorbed
      molecules.
AB  - Density functional theory calculations are often used to interpret experimental
      shifts in core level binding energies. Calculations based on gradient-corrected
      (GC) exchange-correlation functionals are known to reproduce measured core level
      shifts (CLS) of isolated molecules and metal surfaces with reasonable accuracy.
      In the present study, we discuss a series of examples where the shifts calculated
      within a GC-functional significantly deviate from the experimental values, namely
      the CLS of C 1s in ethyl trifluoroacetate, Pd 3d in PdO and the O 1s shift for CO
      adsorbed on PdO(101). The deviations are traced to effects of the electronic self
      interaction error with GC-functionals and substantially better agreements between
      calculated and measured CLS are obtained when a fraction of exact exchange is
      used in the exchange-correlation functional. 

PMID- 25053334
TI  - Local pressure components and interfacial tension at a liquid-solid interface
      obtained by the perturbative method in the Lennard-Jones system.
AB  - A classical molecular dynamics simulation was conducted for a system composed of
      fluid molecules between two planar solid surfaces, and whose interactions are
      described by the 12-6 Lennard-Jones form. This paper presents a general
      description of the pressure components and interfacial tension at a fluid-solid
      interface obtained by the perturbative method on the basis of statistical
      thermodynamics, proposes a method to consider the pressure components tangential
      to an interface which are affected by interactions with solid atoms, and applies
      this method to the calculation system. The description of the perturbative method
      is extended to subsystems, and the local pressure components and interfacial
      tension at a liquid-solid interface are obtained and examined in one- and two
      dimensions. The results are compared with those obtained by two alternative
      methods: (a) an evaluation of the intermolecular force acting on a plane, and (b)
      the conventional method based on the virial expression. The accuracy of the
      numerical results is examined through the comparison of the results obtained by
      each method. The calculated local pressure components and interfacial tension of
      the fluid at a liquid-solid interface agreed well with the results of the two
      alternative methods at each local position in one dimension. In two dimensions,
      the results showed a characteristic profile of the tangential pressure component
      which depended on the direction tangential to the liquid-solid interface, which
      agreed with that obtained by the evaluation of the intermolecular force acting on
      a plane in the present study. Such good agreement suggests that the perturbative
      method on the basis of statistical thermodynamics used in this study is valid to
      obtain the local pressure components and interfacial tension at a liquid-solid
      interface. 

PMID- 25053335
TI  - Well-ordered monolayers of alkali-doped coronene and picene: molecular
      arrangements and electronic structures.
AB  - Adsorptions of alkali metals (such as K and Li) on monolayers of coronene and
      picene realize the formation of ordered phases, which serve as well-defined model
      systems for metal-intercalated aromatic superconductors. Upon alkali-doping of
      the monolayers of coronene and picene, scanning tunneling microscopy and X-ray
      absorption spectroscopy revealed the rearrangement of the entire molecular layer.
      The K-induced reconstruction of both monolayers resulted in the formation of a
      structure with a herringbone-like arrangement of molecules, suggesting the
      intercalation of alkali metals between molecular planes. Upon reconstruction, a
      shift in both the vacuum level and core levels of coronene was observed as a
      result of a charge transfer from alkali metals to coronene. In addition, a new
      density of states near the Fermi level was formed in both the doped coronene and
      the doped picene monolayers. This characteristic electronic feature of the
      ordered monolayer has been also reported in the multilayer picene films, ensuring
      that the present monolayer can model the properties of the metal-intercalated
      aromatic hydrocarbons. It is suggested that the electronic structure near the
      Fermi level is sensitive to the molecular arrangement, and that both the strict
      control and determinations of the molecular structure in the doped phase should
      be important for the determination of the electronic structure of these
      materials. 

PMID- 25053336
TI  - Form factor of pNIPAM microgels in overpacked states.
AB  - We study the form factor of thermoresponsive microgels based on poly(N
      isopropylacrylamide) at high generalized volume fractions, zeta, where the
      particles must shrink or interpenetrate to fit into the available space. Small
      angle neutron scattering with contrast matching techniques is used to determine
      the particle form factor. We find that the particle size is constant up to a
      volume fraction roughly between random close packing and space filling. Beyond
      this point, the particle size decreases with increasing particle concentration;
      this decrease is found to occur with little interpenetration. Noteworthily, the
      suspensions remain liquid-like for zeta larger than 1, emphasizing the importance
      of particle softness in determining suspension behavior. 

PMID- 25053337
TI  - Intramolecular relaxation of flexible dendrimers with excluded volume.
AB  - The mechanical and dielectric relaxation moduli of dendrimers with the excluded
      volume interactions are theoretically investigated within the framework of Rouse
      Zimm theory. The excluded volume interactions in dendrimers are expressed in
      terms of the effective co-volume between nearest non-bonded monomers, modeled
      through the delta function pseudopotential. These short range interactions play a
      decisive role in determining the mechanical moduli of dendrimers. The
      characteristic feature of excluded volume effect in the mechanical moduli is
      typically revealed in the intermediate frequency regime, where dendrimers with
      varied strengths of excluded volume interactions display power-law scaling
      relations with frequency. The value of the power-law scaling exponents for the
      mechanical moduli exactly matches with the earlier results for dendrimers in good
      solvent conditions. The mechanical moduli are dominated by the smaller
      eigenvalues in the low frequency region corresponding to the collective modes
      with smaller relaxation rates, which increase with the corresponding increase of
      the excluded volume interactions. The local modes are practically independent of
      excluded volume. A cross-over between the loss and storage moduli is observed at
      the intermediate frequency regime. The position of this cross-over shifts towards
      the low frequency region with the decrease in the strength of the excluded
      volume, which resembles the behavior of dendrimers with the variation of
      temperature as reported in an earlier experimental work. The structure of
      dendrimers show a conspicuous change as a function of the effective co-volume
      between the nearest non-bonded monomers. The real part of dielectric relaxation
      moduli remains unchanged by varying excluded volume parameters, while its
      imaginary part varies with the change in strength of excluded volumes for the
      entire range of frequency except in the high frequency regime. A comparison with
      the model semiflexible dendrimers show that in such densely packed molecules the
      mechanical relaxation moduli are strongly affected by the short-ranged excluded
      volume interactions between the nearest non-bonded monomers. 

PMID- 25053338
TI  - Percolation thresholds for polydisperse circular disks: a lattice-based
      exploration.
AB  - The percolation threshold for polydisperse systems of (i) isotropically oriented,
      and (ii) perfectly aligned, circular disks is calculated within an analogy to a
      lattice model. Our results are expressed in terms of moments of the distribution
      function over the disk radii, and they closely resemble findings obtained from an
      integral equation approach. The threshold is found to be quite sensitive to
      polydispersity in the disk radii and, for monodisperse systems, to approach a
      plateau for large values of the aspect ratio (thickness to diameter ratio). A
      similar plateau is found for disks with perfectly nematic orientational order,
      for which the percolation threshold always exceeds that for identical systems of
      disks that are oriented isotropically. 

PMID- 25053339
TI  - Anomalous dynamics of binary colloidal mixtures over a potential barrier: effect
      of depletion interaction.
AB  - The dynamics of a binary colloidal mixture under the influence of an external
      potential barrier has been studied by molecular dynamics simulations. The
      attractive depletion interaction between the barrier and larger particles fastens
      the dynamics of the larger particles over the potential barrier. At low
      temperatures, depletion interactions cause the larger particles to diffuse faster
      than smaller particles, which is counterintuitive. The repulsive barrier leads
      the small particles to undergo an anomalous diffusion which resembles the
      dynamics of systems undergoing a glass transition, while the larger particles
      undergo normal diffusion even at very low temperature. 

PMID- 25053340
TI  - Modeling of fluorescence line-narrowed spectra in weakly coupled dimers in the
      presence of excitation energy transfer.
AB  - This work describes simple analytical formulas to describe the fluorescence line
      narrowed (FLN) spectra of weakly coupled chromophores in the presence of
      excitation energy transfer (EET). Modeling studies for dimer systems (assuming
      low fluence and weak coupling) show that the FLN spectra (including absorption
      and emission spectra) calculated for various dimers using our model are in good
      agreement with spectra calculated by: (i) the simple convolution method and (ii)
      the more rigorous treatment using the Redfield approach [T. Renger and R. A.
      Marcus, J. Chem. Phys. 116, 9997 (2002)]. The calculated FLN spectra in the
      presence of EET of all three approaches are very similar. We argue that our
      approach provides a simplified and computationally more efficient description of
      FLN spectra in the presence of EET. This method also has been applied to FLN
      spectra obtained for the CP47 antenna complex of Photosystem II reported by
      Neupane et al. [J. Am. Chem. Soc. 132, 4214 (2010)], which indicated the presence
      of uncorrelated EET between pigments contributing to the two lowest energy
      (overlapping) exciton states, each mostly localized on a single chromophore.
      Calculated and experimental FLN spectra for CP47 complex show very good
      qualitative agreement. 

PMID- 25053341
TI  - Coarse-grained modeling of DNA oligomer hybridization: length, sequence, and salt
      effects.
AB  - A recently published coarse-grained DNA model [D. M. Hinckley, G. S. Freeman, J.
      K. Whitmer, and J. J. de Pablo, J. Chem. Phys. 139, 144903 (2013)] is used to
      study the hybridization mechanism of DNA oligomers. Forward flux sampling is used
      to construct ensembles of reactive trajectories from which the effects of
      sequence, length, and ionic strength are revealed. Heterogeneous sequences are
      observed to hybridize via the canonical zippering mechanism. In contrast,
      homogeneous sequences hybridize through a slithering mechanism, while more
      complex base pair displacement processes are observed for repetitive sequences.
      In all cases, the formation of non-native base pairs leads to an increase in the
      observed hybridization rate constants beyond those observed in sequences where
      only native base pairs are permitted. The scaling of rate constants with length
      is captured by extending existing hybridization theories to account for the
      formation of non-native base pairs. Furthermore, that scaling is found to be
      similar for oligomeric and polymeric systems, suggesting that similar physics is
      involved. 

PMID- 25053342
TI  - Periodic and stochastic thermal modulation of protein folding kinetics.
AB  - Chemical reactions are usually observed either by relaxation of a bulk sample
      after applying a sudden external perturbation, or by intrinsic fluctuations of a
      few molecules. Here we show that the two ideas can be combined to measure protein
      folding kinetics, either by periodic thermal modulation, or by creating
      artificial thermal noise that greatly exceeds natural thermal fluctuations. We
      study the folding reaction of the enzyme phosphoglycerate kinase driven by
      periodic temperature waveforms. As the temperature waveform unfolds and refolds
      the protein, its fluorescence color changes due to FRET (Forster resonant Energy
      Transfer) of two donor/acceptor fluorophores labeling the protein. We adapt a
      simple model of periodically driven kinetics that nicely fits the data at all
      temperatures and driving frequencies: The phase shifts of the periodic donor and
      acceptor fluorescence signals as a function of driving frequency reveal reaction
      rates. We also drive the reaction with stochastic temperature waveforms that
      produce thermal fluctuations much greater than natural fluctuations in the bulk.
      Such artificial thermal noise allows the recovery of weak underlying signals due
      to protein folding kinetics. This opens up the possibility for future detection
      of a stochastic resonance for protein folding subject to noise with controllable
      amplitude. 

PMID- 25053345
TI  - miR-34a is an intracellular and exosomal predictive biomarker for response to
      docetaxel with clinical relevance to prostate cancer progression.
AB  - BACKGROUND: Docetaxel-resistance limits successful treatment of castration
      resistant prostate cancer. We previously demonstrated that extracellular vesicles
      (exosomes) may play a role in regulating docetaxel resistance. Here, we
      investigated intracellular and extracellular (exosomal) miRNAs related to
      docetaxel resistance. METHODS: Following global miRNA profiling of cell line
      models of docetaxel-resistance and their corresponding exosomes, we investigated
      the clinical relevance of four selected miRNAs (miR-598, miR-34a, miR-146a, miR
      148a) in four publically available clinical cohorts representing both primary and
      advanced disease in tissue and urine specimens. One of these miRNAs, miR-34a was
      selected for functional evaluation by miRNA inhibition and over-expression in
      vitro. We further assessed the panel of miRNAs for their combined clinical
      relevance as a biomarker signature by examining their common predicted targets.
      RESULTS: A strong correlation was found between the detection of miRNAs in
      exosomes and their corresponding cells of origin. Of the miRNAs chosen for
      further validation and clinical assessment, decreased miR-34a levels showed
      substantial clinical relevance and so was chosen for further analysis.
      Manipulating miR-34a in prostate cancer cells confirms that this miRNA regulates
      BCL-2 and may, in part, regulate response to docetaxel. When combined, these
      miRNAs are predicted to regulate a range of common mRNA targets, two of which
      (e.g., SNCA, SCL7A5) demonstrate a strong relationship with prostate cancer
      progression and poor prognosis. CONCLUSIONS: This study supports the
      extracellular environment as an important source of minimally invasive predictive
      biomarkers representing their cellular origin. Using miR-34a as example, we
      showed that biomarkers identified in this manner may also hold functional
      relevance.

PMID- 25053346
TI  - Risk factors for retinopathy of prematurity: insights from outlier infants.
AB  - PURPOSE: To investigate the characteristics of outlier infants for insights into
      ROP risk. METHODS: Chart data were collected from 1,354 infants screened for ROP
      at Weill Cornell Medical Center and Columbia University Medical Center. ROP exam
      results and clinical risk factors were recorded. The cohort was stratified by
      weight, highest ROP stage, and need for ROP treatment. Descriptive and
      correlational statistics were performed. RESULTS: For the overall cohort,
      regression analysis found that birth weight (OR: 0.741 per 100 g; 95 % CI: 0.606,
      0.905), gestational age at birth (OR: 0.563 per week; 95 % CI: 0.454, 0.697),
      multiple gestation (OR 2.02, 95 % CI: 1.15, 3.56), bronchopulmonary dysplasia
      (OR: 4.68, 95 % CI: 1.93, 11.35), and necrotizing enterocolitis (OR 2.80, 95 %
      CI: 1.40, 5.16) were independent risk factors for treatment-requiring ROP. Black
      race was found to be a protective factor for treatment-requiring ROP (OR 0.244,
      95 % CI: 0.095, 0.626). Among 15 infants with BW <500 g, there were no
      significant differences in any clinical risk factors between the 12 (80 %) with
      ROP vs the three (20 %) without ROP. Similarly, among infants with BW >1500 g,
      the 17 (9 %) with ROP only differed from the 166 (91 %) without ROP with respect
      to a higher incidence of necrotizing enterocolitis among those with ROP (11.8 %
      vs 0 %). CONCLUSIONS: Although known clinical risk factors were predictive of ROP
      stage and need for laser treatment in this cohort, they were not significantly
      associated with ROP at extremes of birth weight. This suggests that other
      clinical, maternal, or genetic factors may protect from or predispose to ROP.

PMID- 25053347
TI  - Multivalent interactions regulate signal transduction in a self-assembled Hg2+
      sensor.
AB  - A self-assembled sensing system able to detect Hg(2+) at low nanomolar
      concentrations is reported that operates through a signal transduction pathway
      involving multivalent interactions. The analyte causes dimerization of low
      affinity ligands, resulting in a complex with a high affinity for a multivalent
      monolayer-protected gold nanoparticle (AuNP). This complex displaces a quenched
      fluorescent reporter from the AuNP, resulting in a turn ON of fluorescence. It is
      shown that the strength of the output signal can be regulated by tuning the
      multivalent interactions between the complex and the NP. Finally, it is shown
      that multivalent interactions drive the self-selection of a high-affinity complex
      from a mixture of low-affinity ligands. 

PMID- 25053348
TI  - The effect of different drugs on the preparation and biological outcomes of
      plasma rich in growth factors.
AB  - Chronic diseases are the major contributors to the global burden of disease and
      involve prodigious consumption of various drugs that usually affect platelet
      function. The autologous technology of plasma rich in growth factors (PRGF)
      provides a biological approach using autologous platelets as a reservoir and
      local delivery of proteins to promote tissue healing. The purpose of this study
      was to evaluate the effect of the consumption of acetylsalicylic acid,
      acenocoumarol and glucosamine sulfate on the preparation as well as on the
      biological properties of the PRGF technology. Clotting time and platelet
      activation of PRGF was evaluated. The latter was performed by flow cytometry.
      PRGF growth factor content and the release of various biomolecules by gingival
      fibroblasts were quantified by enzyme-linked immunosorbent assay. Cell
      proliferation was evaluated by means of a fluorescence-based method and cell
      migration was performed on culture inserts. None of the parameters evaluated was
      modified by the consumption of any of the three drugs tested; only the plasma of
      patients who had consumed acetylsalicylic acid and acenocoumarol expressed
      greater gingival fibroblast migration compared to plasma control. The intake of
      acetylsalicylic acid, acenocoumarol and glucosamine sulfate does not alter the
      preparation and biological properties of the autologous technology of PRGF.

PMID- 25053350
TI  - Predictors of quality of life in patients evaluated for liver transplantation.
AB  - INTRODUCTION: Health-related quality of life (HRQOL) is severely impaired in
      advanced liver disease. The purpose of this study was to evaluate the impact of
      actual liver function and disease-specific factors on HRQOL of patients evaluated
      for liver transplantation. PATIENTS AND METHODS: Disease-specific QOL was
      analyzed in 142 patients evaluated for liver transplantation using the German
      version of the Chronic Liver Disease Questionnaire (CLDQ-D). We performed
      quantitative liver function tests and collected clinical and demographical data
      of patients after their referral to our transplant department. Values were
      correlated with CLDQ-D scores. RESULTS: Neither model for end-stage liver disease
      (MELD) nor dynamic liver function test results were related to quality of life.
      Serum albumin concentration was a strong but not independent factor correlated
      with global CLDQ-D (r = 0.269, p < 0.001). Independent predictors of global CLDQ
      D were ascites and butyrylcholinesterase serum concentration (B = -0.486, p <
      0.001 and B = 0.196, p = 0.002, respectively). CONCLUSION: Actual liver function
      is not related to decreased quality of life, whereas ascites and hypoproteinemia
      represent the major factors influencing physical and social aspects of daily life
      in potential liver transplant candidates.

PMID- 25053349
TI  - Evaluation of accuracy of B-spline transformation-based deformable image
      registration with different parameter settings for thoracic images.
AB  - Deformable image registration (DIR) is fundamental technique for adaptive
      radiotherapy and image-guided radiotherapy. However, further improvement of DIR
      is still needed. We evaluated the accuracy of B-spline transformation-based DIR
      implemented in elastix. This registration package is largely based on the Insight
      Segmentation and Registration Toolkit (ITK), and several new functions were
      implemented to achieve high DIR accuracy. The purpose of this study was to
      clarify whether new functions implemented in elastix are useful for improving DIR
      accuracy. Thoracic 4D computed tomography images of ten patients with esophageal
      or lung cancer were studied. Datasets for these patients were provided by DIR-lab
      (dir-lab.com) and included a coordinate list of anatomical landmarks that had
      been manually identified. DIR between peak-inhale and peak-exhale images was
      performed with four types of parameter settings. The first one represents
      original ITK (Parameter 1). The second employs the new function of elastix
      (Parameter 2), and the third was created to verify whether new functions improve
      DIR accuracy while keeping computational time (Parameter 3). The last one
      partially employs a new function (Parameter 4). Registration errors for these
      parameter settings were calculated using the manually determined landmark pairs.
      3D registration errors with standard deviation over all cases were 1.78 (1.57),
      1.28 (1.10), 1.44 (1.09) and 1.36 (1.35) mm for Parameter 1, 2, 3 and 4,
      respectively, indicating that the new functions are useful for improving DIR
      accuracy, even while maintaining the computational time, and this B-spline-based
      DIR could be used clinically to achieve high-accuracy adaptive radiotherapy.

PMID- 25053357
TI  - Development. Mechanical forces linked to organ growth.
AB  - Jub protein couples cytoskeletal tension to growth by modulating Hippo
      signalling.

PMID- 25053358
TI  - Small RNAs break out: the molecular cell biology of mobile small RNAs.
AB  - Small RNAs that function in a non-cell autonomous manner are becoming
      increasingly recognized as regulatory molecules with the potential to transmit
      information between cells, organisms and species. In plants and nematodes, small
      RNA mobility can be genetically dissected to provide information about the nature
      of the mobile RNA species, their distribution in the organism and inside cells,
      as well as the cellular machinery required for mobility, including channel
      proteins and cellular trafficking factors. Mobile RNAs function in antiviral
      defence, cell signalling and gene expression regulation, and might also mediate
      transgenerational epigenetic inheritance. 

PMID- 25053360
TI  - Characterizing the genetic differences between two distinct migrant groups from
      Indo-European and Dravidian speaking populations in India.
AB  - BACKGROUND: India is home to many ethnically and linguistically diverse
      populations. It is hypothesized that history of invasions by people from Persia
      and Central Asia, who are referred as Aryans in Hindu Holy Scriptures, had a
      defining role in shaping the Indian population canvas. A shift in spoken
      languages from Dravidian languages to Indo-European languages around 1500 B.C. is
      central to the Aryan Invasion Theory. Here we investigate the genetic differences
      between two sub-populations of India consisting of: (1) The Indo-European
      language speaking Gujarati Indians with genome-wide data from the International
      HapMap Project; and (2) the Dravidian language speaking Tamil Indians with genome
      wide data from the Singapore Genome Variation Project. RESULTS: We implemented
      three population genetics measures to identify genomic regions that are
      significantly differentiated between the two Indian populations originating from
      the north and south of India. These measures singled out genomic regions with:
      (i) SNPs exhibiting significant variation in allele frequencies in the two Indian
      populations; and (ii) differential signals of positive natural selection as
      quantified by the integrated haplotype score (iHS) and cross-population extended
      haplotype homozygosity (XP-EHH). One of the regions that emerged spans the
      SLC24A5 gene that has been functionally shown to affect skin pigmentation, with a
      higher degree of genetic sharing between Gujarati Indians and Europeans.
      CONCLUSIONS: Our finding points to a gene-flow from Europe to north India that
      provides an explanation for the lighter skin tones present in North Indians in
      comparison to South Indians.

PMID- 25053359
TI  - The growing landscape of lysine acetylation links metabolism and cell signalling.
AB  - Lysine acetylation is a conserved protein post-translational modification that
      links acetyl-coenzyme A metabolism and cellular signalling. Recent advances in
      the identification and quantification of lysine acetylation by mass spectrometry
      have increased our understanding of lysine acetylation, implicating it in many
      biological processes through the regulation of protein interactions, activity and
      localization. In addition, proteins are frequently modified by other types of
      acylations, such as formylation, butyrylation, propionylation, succinylation,
      malonylation, myristoylation, glutarylation and crotonylation. The intricate link
      between lysine acylation and cellular metabolism has been clarified by the
      occurrence of several such metabolite-sensitive acylations and their selective
      removal by sirtuin deacylases. These emerging findings point to new functions for
      different lysine acylations and deacylating enzymes and also highlight the
      mechanisms by which acetylation regulates various cellular processes. 

PMID- 25053362
TI  - Exploring the relationship of functional network connectivity to latent
      trajectories of alcohol use and risky sex.
AB  - Alcohol use is a major risk factor associated with unprotected sexual behavior,
      leading to higher risk of sexually transmitted infections (STI) including the
      human immunodeficiency virus (HIV). Emerging largely cross-sectional data suggest
      functional network connectivity strength is associated with problematic alcohol
      use, and as evidence supports a relationship between risky sexual behaviors and
      alcohol use, we hypothesized that functional connectivity might be associated
      with both categories of risk behavior. As part of a sexual risk reduction
      intervention study, juvenile justice-involved adolescents (N = 239) underwent a
      baseline functional magnetic resonance imaging scan and completed questionnaires
      about their alcohol use and risky sexual behavior at 3-month intervals over 12
      months of follow up. To test both cross-sectional and longitudinal relationships
      between alcohol use and sexual risk behaviors, we estimated a parallel process
      latent growth model that simultaneously modeled the trajectories of alcohol use
      and sexual risk behavior. Functional connectivity strength was included as an
      exogenous variable to evaluate its relationship with level of risk and change in
      risk over time in both behaviors. Associations were found between baseline
      alcohol use and risky sex, and between longitudinal trajectories of alcohol use
      and risky sex. Network functional connectivity strength of the dorsal default
      mode network was associated with initial and longitudinal alcohol use, which may
      suggest that self-awareness of the effects of alcohol could serve as a useful
      target to decrease subsequent risky sexual behavior in adolescence.

PMID- 25053361
TI  - Alcohol enhances HIV infection of cord blood monocyte-derived macrophages.
AB  - Alcohol consumption or alcohol abuse is common among pregnant HIV(+) women and
      has been identified as a potential behavioral risk factor for the transmission of
      HIV. In this study, we examined the impact of alcohol on HIV infection of cord
      blood monocyte-derived macrophages (CBMDM). We demonstrated that alcohol
      treatment of CBMDM significantly enhanced HIV infection of CBMDM. Investigation
      of the mechanisms of alcohol action on HIV demonstrated that alcohol inhibited
      the expression of several HIV restriction factors, including anti-HIV microRNAs,
      APOBEC3G and APOBEC3H. Additionally, alcohol also suppressed the expression of
      IFN regulatory factor 7 (IRF-7) and retinoic acid-inducible gene I (RIG-I), an
      intracellular sensor of viral infection. The suppression of these IFN regulatory
      factors was associated with reduced expression of type I IFN. These experimental
      findings suggest that maternal alcohol consumption may facilitate HIV infection,
      promoting vertical transmission of HIV. 

PMID- 25053363
TI  - HIV-1, HCV and alcohol in the CNS: potential interactions and effects on
      neuroinflammation.
AB  - Approximately 25% of the HIV-1 positive population is also infected with HCV. The
      effects of alcohol on HIV-1 or HCV infection have been a research topic of
      interest due to the high prevalence of alcohol use in these infected patient
      populations. Although it has long been known that HIV-1 infects the brain, it has
      only been a little more than a decade since HCV infection of the CNS has been
      characterized. Both viruses are capable of infecting and replicating in microglia
      and increasing the expression of proinflammatory cytokines and chemokines,
      including IL-6 and IL-8. Investigations focusing on the effects of HIV-1, HCV or
      alcohol on neuroinflammation have demonstrated that these agents are capable of
      acting through overlapping signaling pathways, including MAPK signaling
      molecules. In addition, HIV-1, HCV and alcohol have been demonstrated to increase
      permeability of the blood-brain barrier. Patients infected with either HIV-1 or
      HCV, or those who use alcohol, exhibit metabolic abnormalities in the CNS that
      result in altered levels of n-acetyl aspartate, choline and creatine in various
      regions of the brain. Treatment of HIV/HCV co-infection in alcohol users is
      complicated by drug-drug interactions, as well as the effects of alcohol on drug
      metabolism. The drug-drug interactions between the antiretrovirals and the
      antivirals, as well as the effects of alcohol on drug metabolism, complicate
      existing models of CNS penetration, making it difficult to assess the efficacy of
      treatment on CNS infection. 

PMID- 25053364
TI  - Differences in sexual risk behaviors between lower and higher frequency alcohol
      using African-American adolescent females.
AB  - BACKGROUND: To examine differences between lower and higher frequency alcohol
      users in sexual behaviors and psychosocial correlates of risk for HIV among young
      African-American females. METHODS: Data were collected from sexually active
      African-American females aged 15-20 years, seeking services at a STD clinic in
      Atlanta, GA, to assess sexual behavior, correlates of risk, and a non-disease
      biological marker of unprotected vaginal sex. RESULTS: Number of drinking
      occasions was significantly related to three of four psychosocial correlates and
      with all self-reporting sexual behavior measures. Also, heavier drinking per
      occasion was associated with the presence of semen in vaginal fluid. CONCLUSION:
      Non-abuse levels of drinking were related to increased sexual risk-taking in this
      sample of young African- American females. Incorporating messages about the
      intersection of alcohol use and sexual decision making into HIV/STD prevention
      programs would strengthen STD prevention messaging in this vulnerable population.

PMID- 25053366
TI  - Brain derived neurotrophic factor and cognitive status: the delicate balance
      among people living with HIV, with and without alcohol abuse.
AB  - INTRODUCTION: The advent of combination antiretroviral therapy(cART) has lead to
      a significant reduction in morbidity and mortality among people living with
      HIV(PLWH). However, HIV-associated neurocognitive disorders (HAND) still remain a
      significant problem. One possible mechanism for the persistence of these
      disorders is through the effect of HIV on brain-derived neurotrophic factor
      (BDNF). BDNF is influenced by various factors including hazardous alcohol use
      (HAU), which is prevalent among PLWH. This study attempts to elucidate the
      relationships between HAU, BDNF and HAND. METHODS: Cross-sectional analyses were
      conducted on a sample of 199 hazardous alcohol users and 198 non-HAU living with
      HIV. Members of each group were matched according to sociodemographic
      characteristics and CD4 count. Research procedures included validated
      questionnaires, neuropsychological assessments and a blood sample to obtain BDNF
      and immune measurements. RESULTS: Hazardous alcohol users showed either
      significantly lower or significantly higher BDNF levels compared to the Non
      hazardous (OR=1,4; 95% CI: 1-2.1, p = 0.003). Therefore, for additional analyses,
      subjects were categorized based on BDNF values in: Group 1 < 4000, Group 2: 4001
      7,999 (reference group), and Group 3 for those >8,000 pg/mL. Groups 1 and 3
      performed significantly worse than those in Group 2 in the domains of processing
      speed, auditory-verbal and visuospatial learning and memory. Multivariate
      analyses confirmed that HAU and BDNF are significant contributors of HAND.
      CONCLUSION: Our findings offer novel insights into the relationships between
      BDNF, and alcohol use among PLWH. Our results also lend support to expanding
      clinical movement to use BDNF as an intervention target for PLWH, in those with
      evidence of deficiencies, and highlight the importance of including HAUat the
      inception of clinical trials.

PMID- 25053365
TI  - Biomedical consequences of alcohol use disorders in the HIV-infected host.
AB  - Alcohol abuse is the most common and costly form of drug abuse in the United
      States. It is well known that alcohol abuse contributes to risky behaviors
      associated with greater incidence of human immunodeficiency virus (HIV)
      infections. As HIV has become a more chronic disease since the introduction of
      antiretroviral therapy, it is expected that alcohol use disorders will have an
      adverse effect on the health of HIV-infected patients. The biomedical
      consequences of acute and chronic alcohol abuse are multisystemic. Based on what
      is currently known of the comorbid and pathophysiological conditions resulting
      from HIV infection in people with alcohol use disorders, chronic alcohol abuse
      appears to alter the virus infectivity, the immune response of the host, and the
      progression of disease and tissue injury, with specific impact on disease
      progression. The combined insult of alcohol abuse and HIV affects organ systems,
      including the central nervous system, the immune system, the liver, heart, and
      lungs, and the musculoskeletal system. Here we outline the major pathological
      consequences of alcohol abuse in the HIV-infected individual, emphasizing its
      impact on immunomodulation, erosion of lean body mass associated with AIDS
      wasting, and lipodystrophy. We conclude that interventions focused on reducing or
      avoiding alcohol abuse are likely to be important in decreasing morbidity and
      improving outcomes in people living with HIV/AIDS. 

PMID- 25053367
TI  - Chronic alcohol abuse and HIV disease progression: studies with the non-human
      primate model.
AB  - The populations at risk for HIV infection, as well as those living with HIV,
      overlap with populations that engage in heavy alcohol consumption. Alcohol use
      has been associated with high-risk sexual behavior and an increased likelihood of
      acquiring HIV, as well as poor outcome measures of disease such as increased
      viral loads and declines in CD4+ T lymphocytes among those living with HIV
      infections. It is difficult to discern the biological mechanisms by which alcohol
      use affects the virus:host interaction in human populations due to the numerous
      variables introduced by human behavior. The rhesus macaque infected with simian
      immunodeficiency virus has served as an invaluable model for understanding HIV
      disease and transmission, and thus, provides an ideal model to evaluate the
      effects of chronic alcohol use on viral infection and disease progression in a
      controlled environment. In this review, we describe the different macaque models
      of chronic alcohol consumption and summarize the studies conducted with SIV and
      alcohol. Collectively, they have shown that chronic alcohol consumption results
      in higher levels of plasma virus and alterations in immune cell populations that
      potentiate SIV replication. They also demonstrate a significant impact of chronic
      alcohol use on SIV-disease progression and survival. These studies highlight the
      utility of the rhesus macaque in deciphering the biological effects of alcohol on
      HIV disease. Future studies with this well-established model will address the
      biological influence of alcohol use on susceptibility to HIV, as well as the
      efficacy of anti-retroviral therapy. 

PMID- 25053369
TI  - [Metastasis from the cecal appendix as the first manifestation of a pancreatic
      carcinoma. Atypical cecal metastasis].

PMID- 25053368
TI  - Alcohol abuse and HIV infection: role of DRD2.
AB  - According to a survey from the HIV Cost and Services Utilization Study (HCSUS),
      approximately 53% of HIV-infected patients reported drinking alcohol and 8% were
      classified as heavy drinkers. The role of alcohol as a risk factor for HIV
      infection has been widely studied and recent research has found a significant
      association between heavy alcohol consumption and lower levels of CD4 T cells
      among HIV-infected alcoholics. Although there is evidence on the role of alcohol
      as a risk factor for HIV transmission and disease progression, there is a need
      for population studies to determine the genetic mechanisms that affect alcohol's
      role in HIV disease progression. One of the mechanisms of interest is the
      dopaminergic system. To date, the effects of dopamine on HIV neuroimmune
      pathogenesis are not well understood; however, dopaminergic neural degeneration
      due to HIV is known to occur by viral invasion into the brain via immune cells,
      and modulation of dopamine in the CNS may be a common mechanism by which
      different types of substances of abuse impact HIV disease progression. Although
      previous studies have shown an association of D(2) dopamine receptor (DRD2)
      polymorphisms with severity of alcohol dependence, the expression of this allele
      risk on HIV patients with alcohol dependence has not been systematically
      explored. In the current study, DRD2 Taq1A and C957T SNP genotyping analyses were
      performed in 165 HIV-infected alcohol abusers and the results were examined with
      immune status and CD4 counts. 

PMID- 25053370
TI  - 18 F-Fluoride positron emission tomography/computed tomography for noninvasive in
      vivo quantification of pathophysiological bone metabolism in experimental murine
      arthritis.
AB  - INTRODUCTION: Evaluation of disease severity in experimental models of rheumatoid
      arthritis is inevitably associated with assessment of structural bone damage. A
      noninvasive imaging technology allowing objective quantification of
      pathophysiological alterations of bone structure in rodents could substantially
      extend the methods used to date in preclinical arthritis research for staging of
      autoimmune disease severity or efficacy of therapeutical intervention. Sodium 18
      F-fluoride (18 F-NaF) is a bone-seeking tracer well-suited for molecular imaging.
      Therefore, we systematically examined the use of 18 F-NaF positron emission
      tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate
      isomerase (G6PI)-induced arthritis for quantification of pathological bone
      metabolism. METHODS: F-fluoride was injected into mice before disease onset and
      at various time points of progressing experimental arthritis. Radioisotope
      accumulation in joints in the fore- and hindpaws was analyzed by PET
      measurements. For validation of bone metabolism quantified by 18 F-fluoride PET,
      bone surface parameters of high-resolution MUCT measurements were used. RESULTS:
      Before clinical arthritis onset, no distinct accumulation of 18 F-fluoride was
      detectable in the fore- and hindlimbs of mice immunized with G6PI. In the course
      of experimental autoimmune disease, 18 F-fluoride bone uptake was increased at
      sites of enhanced bone metabolism caused by pathophysiological processes of
      autoimmune disease. Moreover, 18 F-fluoride signaling at different stages of G6PI
      induced arthritis was significantly correlated with the degree of bone
      destruction. CT enabled identification of exact localization of 18 F-fluoride
      signaling in bone and soft tissue. CONCLUSIONS: The results of this study suggest
      that small-animal PET/CT using 18 F-fluoride as a tracer is a feasible method for
      quantitative assessment of pathophysiological bone metabolism in experimental
      arthritis. Furthermore, the possibility to perform repeated noninvasive
      measurements in vivo allows longitudinal study of therapeutical intervention
      monitoring.

PMID- 25053371
TI  - Agreement of high definition oscillometry with direct arterial blood pressure
      measurement at different blood pressure ranges in horses under general
      anaesthesia.
AB  - OBJECTIVE: To determine the agreement of high definition oscillometry (HDO) with
      direct arterial blood pressure measurements in normotensive, hypotensive and
      hypertensive horses during general anaesthesia. STUDY DESIGN: Experimental study.
      ANIMALS: Seven healthy warmblood horses, aged 3-11 years, weighing 470-565 kg.
      METHODS: Measurements from a HDO device with the cuff placed around the base of
      the tail were compared with pressures measured invasively from the facial artery.
      High blood pressures were induced by intravenous (IV) administration of
      dobutamine (5 MUg kg(-1) minute(-1)) over ten minutes followed by norepinephrine
      (0.1 mg kg(-1) IV) and low pressures by increasing the inspired fraction of
      isoflurane and administration of nitroglycerine (0.05 mg kg(-1) IV). For analysis
      three pressure levels were determined: high (MAP>110 mmHg), normal (60
      mmHg<MAP<110 mmHg) and low (MAP< 60 mmHg). Bland-Altman analysis was used for
      comparison between non-invasive and invasive measurements. RESULTS: A total of
      245 paired measurements of systolic (SAP), mean (MAP) and diastolic (DAP)
      pressures were obtained. The HDO device underestimated blood pressure at
      hypertensive and normotensive levels and overestimated blood pressure at
      hypotensive levels. Best agreement was obtained for SAP and MAP within
      normotensive limits. At normotension, bias +/- standard deviation for SAP, MAP
      and DAP were 0.1 +/- 19.4 mmHg, 0.5 +/- 14.0, 4.7 +/- 15.6, respectively. At high
      pressure levels bias and SD were 26.1 +/- 37.3 (SAP), 4.2 +/- 19.4 (MAP), 1.5 +/-
      16.8 (DAP) and at low pressures -20.0 +/- 20.9 (SAP), -11.4 +/- 19.6 (MAP), -4.7
      +/- 20.1 (DAP), with HDO measurements at a MAP <50 mmHg often failing. CONCLUSION
      AND CLINICAL RELEVANCE: Good agreement with invasive arterial blood pressures was
      obtained with HDO at normotensive levels in horses. At high and low pressure
      ranges HDO was unreliable. Therefore, if haemodynamic instability is expected,
      invasive measurement remains preferable.

PMID- 25053372
TI  - A longitudinal study of factor XIII activity, fibrinogen concentration, platelet
      count and clot strength during normal pregnancy.

PMID- 25053373
TI  - Immunomodulatory effect of melatonin in SK-LU-1 human lung adenocarcinoma cells
      co-cultured with peripheral blood mononuclear cells.
AB  - OBJECTIVES: The anti-cancer potential of melatonin has been examined using a
      variety of experimental approaches. Melatonin immunomodulatory action was
      evaluated against the lung cancer cell line SK-LU-1, in co-culture with human
      peripheral blood mononuclear cells (PBMC). MATERIALS AND METHODS: Melatonin was
      tested on the cell line only after 24 h incubation (direct effect), and on the co
      culture system of SK-LU-1 and PBMC to investigate any indirect effect. Apoptotic
      induction of the cancer cells was assessed using annexin V/PI staining with flow
      cytometric analysis for membrane alteration. Intracellular superoxide anion (O2
      (*-) ) and hydrogen peroxide (H2 O2 ) for intracellular oxidative stress and
      glutathione (GSH) for intracellular anti-oxidation were measured with specific
      fluorescence probes. DNA fractions were measured employing propidium iodide (PI)
      fluorescence staining. RESULTS: High doses of melatonin were directly toxic to SK
      LU-1 cells, while PBMC-mediated indirect effect occurred after moderate doses (1
      MUm). Under co-culture conditions, increases in apoptotic cell death, increase in
      oxidative stress by reduction of GSH and cell cycle arrest in G0 /G1 in SK-LU-1
      cells, were observed as the immunomodulatory effect of melatonin. CONCLUSION:
      Melatonin had indirect effects on lung cancer cells by enhancement of
      immunomodulatory effects, but further studies of mechanism(s) involved are
      needed.

PMID- 25053374
TI  - The influence of knee position on ankle dorsiflexion - a biometric study.
AB  - BACKGROUND: Musculus gastrocnemius tightness (MGT) can be diagnosed by comparing
      ankle dorsiflexion (ADF) with the knee extended and flexed. Although various
      measurement techniques exist, the degree of knee flexion needed to eliminate the
      effect of the gastrocnemius on ADF is still unknown. The aim of this study was to
      identify the minimal degree of knee flexion required to eliminate the restricting
      effect of the musculus gastrocnemius on ADF. METHODS: Bilateral ADF of 20
      asymptomatic volunteers aged 18-40 years (50% female) was assessed prospectively
      at six different degrees of knee flexion (0 degrees , 20 degrees , 30 degrees ,
      45 degrees , 60 degrees , 75 degrees , Lunge). Tests were performed following a
      standardized protocol, non weightbearing and weightbearing, by two observers.
      Statistics comprised of descriptive statistics, t-tests, repeated measurement
      ANOVA and ICC. RESULTS: 20 individuals with a mean age of 27 +/- 4 years were
      tested. No significant side to side differences were observed. The average ADF
      [95% confidence interval] for non weightbearing was 4 degrees  [1 degrees -8
      degrees ] with the knee extended and 20 degrees  [16 degrees -24 degrees ] for
      the knee 75 degrees  flexed. Mean weightbearing ADF was 25 degrees  [22 degrees 
      28 degrees ] for the knee extended and 39 degrees  [36 degrees -42 degrees ] for
      the knee 75 degrees  flexed. The mean differences between 20 degrees  knee
      flexion and full extension were 15 degrees  [12 degrees -18 degrees ] non
      weightbearing and 13 degrees  [11 degrees -16 degrees ] weightbearing.
      Significant differences of ADF were only found between full extension and 20
      degrees  of knee flexion. Further knee flexion did not increase ADF. CONCLUSION:
      Knee flexion of 20 degrees  fully eliminates the ADF restraining effect of the
      gastrocnemius. This knowledge is essential to design a standardized clinical
      examination assessing MGT.

PMID- 25053375
TI  - A direct amygdala-motor pathway for emotional displays to influence action: A
      diffusion tensor imaging study.
AB  - An important evolutionary function of emotions is to prime individuals for
      action. Although functional neuroimaging has provided evidence for such a
      relationship, little is known about the anatomical substrates allowing the limbic
      system to influence cortical motor-related areas. Using diffusion-weighted
      magnetic resonance imaging and probabilistic tractography on a cohort of 40
      participants, we provide evidence of a structural connection between the amygdala
      and motor-related areas (lateral and medial precentral, motor cingulate and
      primary motor cortices, and postcentral gyrus) in humans. We then compare this
      connection with the connections of the amygdala with emotion-related brain areas
      (superior temporal sulcus, fusiform gyrus, orbitofrontal cortex, and lateral
      inferior frontal gyrus) and determine which amygdala nuclei are at the origin of
      these projections. Beyond the well-known subcortical influences over automatic
      and stereotypical emotional behaviors, a direct amygdala-motor pathway might
      provide a mechanism by which the amygdala can influence more complex motor
      behaviors.

PMID- 25053376
TI  - Conservative management or intervention for unruptured brain arteriovenous
      malformations.

PMID- 25053377
TI  - 4C/ID in medical education: How to design an educational program based on whole
      task learning: AMEE Guide No. 93.
AB  - Medical education increasingly stresses that medical students should be prepared
      to take up multiple roles as a health professional. This requires the integrated
      acquisition of multiple competences such as clinical reasoning and decision
      making, communication skills and management skills. To promote such complex
      learning, instructional design has focused on the use of authentic, real-life
      learning tasks that students perform in a real or simulated task environment. The
      four-component instructional design model (4C/ID) model is an instructional
      design model that starts from the use of such tasks and provides students with a
      variety of learning tools facilitating the integrated acquisition of knowledge,
      skills and attitudes. In what follows, we guide the reader on how to implement
      educational programs based on the 4C/ID model and illustrate this with an example
      from general practice education. The developed learning environment is in line
      with the whole-task approach, where a learning domain is considered as a
      coherent, integrated whole and where teaching progresses from offering relatively
      simple, but meaningful, authentic whole tasks to more complex tasks. We describe
      the steps that were taken, from prototype over development to implementation, to
      build five learning modules (patient with diabetes; the young child with fever;
      axial skeleton; care for the elderly and physically undefined symptoms) that all
      focus on the integrated acquisition of the Canadian Medical Education Directives
      for Specialists roles in general practice. Furthermore, a change cycle for
      educational innovation is described that encompasses practice-based challenges
      and pitfalls about the collaboration between different stakeholders (students,
      developers and teachers) and the transition from traditional, fragmented and
      classroom-based learning to integrated and blended learning based on sound
      instructional design principles.

PMID- 25053378
TI  - Evidence-based decision about test scoring rules in clinical anatomy multiple
      choice examinations.
AB  - In theory the formula scoring methods increase the reliability of multiple-choice
      tests in comparison with number-right scoring. This study aimed to evaluate the
      impact of the formula scoring method in clinical anatomy multiple-choice
      examinations, and to compare it with that from the number-right scoring method,
      hoping to achieve an evidence-based decision about test scoring rules. Two
      hundred and ninety-eight students completed an examination in clinical anatomy
      which included 40 multiple-choice questions with five response options each.
      Among these, 245 (82.2%) examinees were assessed according to the number-right
      scoring method (group A) while 53 (17.8%) were assessed according to the formula
      scoring method (group B). The prevalence of passing was significantly higher in
      group A than in group B, after correction of the pass and fail cutoffs for
      guessing (84.9% vs. 62.3%, P = 0.005), keeping a similar reliability in both
      groups (0.7 vs. 0.8, P = 0.094). Pearson Correlation coefficients between
      practical and theoretical examination scores were 0.66 [95%CI = (0.58-0.73)] and
      0.72 [95%CI = (0.56-0.83)] for groups A and B, respectively. Based solely on the
      reliability and validity assessments, the test-maker could therefore use either
      scoring rules; however, if the test-maker also takes into account the students'
      ability to deduce answers with partial knowledge, then the number-right score
      rule is most appropriate.

PMID- 25053379
TI  - Federal environmental and occupational toxicology regulations and reporting
      requirements: a practical approach to what the medical toxicologist needs to
      know, part 2.
AB  - Toxicologists are often called upon to assist in environmental, industrial,
      occupational and public health assessments. Accordingly, medical toxicologists
      may find it prudent to be aware of applicable federal toxicological regulations
      and reporting requirements and of the roles of relevant federal agencies. These
      regulations are numerous, complex, and have evolved and expanded over time,
      making it difficult for toxicologists to sustain a current knowledge base. This
      article reviews the pertinent federal toxicological reporting requirements with
      regards to the Toxic Substances Control Act (TSCA), the Atomic Energy Act (AEA),
      the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource
      Conservation and Recovery Act (RCRA), the Clean Air Act, the Clean Water Act, the
      Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA),
      the Emergency Planning and Community Right to Know Act (EPCRA), the Occupational
      Safety and Health Act, the Department of Transportation, and information about
      the National Response Center. We reference internet-based government resources
      and offer direct links to applicable websites in an attempt to offer rapid and
      current sources of practical information. The format of the article is a series
      of hypothetical scenarios followed by commentary. Discussions of the Safe
      Drinking Water Act and the Food, Drug, and Cosmetic Act and the Dietary
      Supplement Health and Education Act are beyond the scope of this paper. For those
      desiring a more in depth discussion of the relevant federal environmental laws
      and statutes, and applicable case law, the reader is directed to resources such
      as the Environmental Law Handbook, the websites of individual laws found at
      www.epa.gov and the decisions of individual courts of appeal. It is our hope that
      this article provides not only useful practical information for the practicing
      toxicologist, but also serves as a key reference for Medical Toxicology core
      content on environmental laws and regulations.

PMID- 25053380
TI  - Mortality in children with juvenile dermatomyositis: two decades of experience
      from a single tertiary care centre in North India.
AB  - Survival and outcomes have improved considerably among patients with juvenile
      dermatomyositis (JDM) in the west. However, mortality continues to be high in the
      developing world. There is paucity of literature on this aspect of JDM from
      developing countries. We reviewed case files of all patients with JDM registered
      in the Pediatric Rheumatology Clinic, Advanced Pediatrics Centre at the Post
      Graduate Institute of Medical Education and Research, Chandigarh, during the
      period 1993-2013. Seventy-six children were diagnosed to have inflammatory
      myopathy during this period. Of these, 63 had JDM, 3 had polymyositis while 10
      had an overlap syndrome. We had reported 2 deaths out of 33 (8.3 %) patients with
      JDM in 2004, and over the last 9 years, we have encountered five more deaths in
      this group, thereby accounting for a mortality rate of 11.1 % (7/63) over two
      decades of follow-up. In these five children now being described, the mean
      duration between onset of symptoms and institution of appropriate therapy was 9.2
      months. Four children (80 %) had severe muscle weakness needing nasogastric tubes
      at the onset, three (60 %) had cutaneous ulcers and three (60 %) had superadded
      infections. Two children (40 %) had gastrointestinal vasculitis and one of these
      developed an intestinal perforation. Three patients (60 %) had progressive
      pulmonary disease and air leak was identified in two of them. Although the
      prognosis for survival in JDM has steadily improved, in our experience the
      disease remains a serious illness and still carries significant mortality in the
      context of a developing country. 

PMID- 25053381
TI  - General adverse response to cyclophosphamide in Chinese patients with systemic
      autoimmune diseases in recent decade-a single-center retrospective study.
AB  - This study was conducted to investigate the adverse reaction to cyclophosphamide
      (CYC) in Chinese patients with systemic autoimmune diseases. Patients with
      systemic autoimmune diseases who were exposed to CYC and followed up regularly
      for at least 2 years in Rheumatology Department during June 2003 to June 2013
      were enrolled into this study. Participants were divided into per oral (PO) group
      and intravenous (IV) group. The adverse effects to CYC were recorded and
      analyzed. A total of 419 patients were enrolled in this study. The occurrence
      rates of gastrointestinal discomfort, alopecia, myelosuppression, secondary
      infection, abnormal liver function, dizziness/headache, menstrual disturbance and
      reversal to normal menstruation after discontinuation of CYC were 21.5%, 12.4%,
      7.4 %, 3.6%, 3.1%, 3.1%, 30.3% and 31.0%, respectively. None of the patients had
      hemorrhagic cystitis. The significant risk factors for gastrointestinal
      discomfort were female, exposure to CYC for a long time and intravenous route.
      Risk factors for mylosuppression were female and combination with other
      immunosuppressants. Risk factors were female gender for alopecia and older age
      for menstrual disturbance. Female patients were much more likely to have
      gastrointestinal discomfort, mylosuppression and alopecia when CYC was
      administrated intravenously. Risk factors were older age for menstrual
      disturbance and the combination with other immunosuppressants for
      myelosuppression. Hemorrhagic cystitis did not appear in our series for the
      possible reason of prophylactic hydration before intravenous injection and maybe
      racial difference.

PMID- 25053383
TI  - Acute fibular head dislocation in a 27-year-old man.

PMID- 25053382
TI  - Financial stress, parent functioning and adolescent problem behavior: an actor
      partner interdependence approach to family stress processes in low-, middle-, and
      high-income families.
AB  - The family stress model proposes that financial stress experienced by parents is
      associated with problem behavior in adolescents. The present study applied an
      actor-partner interdependence approach to the family stress model and focused on
      low-, middle-, and high-income families to broaden our understanding of the
      pathways by which the financial stress of mothers and fathers are related to
      adolescent outcomes. The study uses dyadic data (N = 798 heterosexual couples)
      from the Relationship between Mothers, Fathers and Children study in which two
      parent families with an adolescent between 11 and 17 years of age participated.
      Path-analytic results indicated that in each of the families the association
      between parents' financial stress and problem behavior in adolescents is mediated
      through parents' depressive symptoms, interparental conflict, and positive
      parenting. Family stress processes also appear to operate in different ways for
      low-, middle-, and high-income families. In addition to a higher absolute level
      of financial stress in low-income families, financial stress experienced by
      mothers and fathers in these families had significant direct and indirect effects
      on problem behavior in adolescents, while in middle- and high-income families
      only significant indirect effects were found. The financial stress of a low
      income mother also had a more detrimental impact on her level of depressive
      feelings than it had on mothers in middle-income families. Furthermore, the study
      revealed gender differences in the pathways of mothers and fathers. Implications
      for research, clinical practice, and policy are also discussed.

PMID- 25053384
TI  - A case of facial puffiness.

PMID- 25053385
TI  - Validation of a novel procedure for quantification of the formation of
      phosphoramide mustard by individuals treated with cyclophosphamide.
AB  - PURPOSE: Use of the patient's body surface area (mg m(-2)) as a basis for dosing
      does not take individual variation in metabolic capacity and rate of clearance
      into account. Here, we evaluated a novel approach for individual monitoring of
      short-lived cytotoxic agents formed from cytostatic drugs such as
      cyclophosphamide (CP). METHODS: The accumulated blood dose of the cytotoxic
      active agent phosphoramide mustard (PAM) formed from CP was measured as a
      reaction product with hemoglobin (Hb adduct). This adduct, N-[2-(2
      oxazolidonyl)ethyl]-valyl Hb (OzVal-Hb), was detached from Hb with the adduct
      FIRE procedureTM, and the formed analyte was quantified using LC-MS/MS. This dose
      biomarker for PAM and the analytical procedure was evaluated in accordance with
      the guidelines on bioanalytical method validation formulated by the European
      Medicine Agency. The evaluated method was applied to quantify blood dose levels
      of PAM in female breast cancer patients (n = 12) before and after three cycles of
      polychemotherapy regimes containing CP. RESULTS: OzVal-Hb, a specific and stable
      biomarker, could be measured with great sensitivity (lower limit of
      quantification = 33 pmol g(-1) Hb), high accuracy (within +/-20 %) and good
      repeatability (CV < 20 %). The inter-individual variability in the blood level of
      this adduct in women with breast cancer (n = 12) who received three doses of CP
      in combination with one or two other cytostatic drugs was 250 % following the
      first dose and approximately 150 % after each subsequent dose. CONCLUSIONS:
      Measurement of the biomarker OzVal-Hb can be used to quantify the short-lived
      cytotoxic agent PAM in a single blood sample drawn several days after therapy.
      This procedure may aid in individualizing doses of CP, thereby improving efficacy
      while both reducing the risk of and increasing the predictability of side
      effects.

PMID- 25053386
TI  - Population pharmacokinetics of peritoneal, plasma ultrafiltrated and protein
      bound oxaliplatin concentrations in patients with disseminated peritoneal cancer
      after intraperitoneal hyperthermic chemoperfusion of oxaliplatin following
      cytoreductive surgery: correlation between oxaliplatin exposure and
      thrombocytopenia.
AB  - PURPOSE: First, to evaluate the peritoneal (IP), plasma ultrafiltrated (UF) and
      protein-bound (B) pharmacokinetics (PK) of oxaliplatin after intraperitoneal
      hyperthermic chemoperfusion (HIPEC) following cytoreductive surgery. Second, to
      evaluate the relationship between oxaliplatin exposure and observed toxicity.
      METHODS: IP, UF, and B concentrations from 75 patients treated by 30-min
      oxaliplatin-based HIPEC procedures were analysed according to a pharmacokinetic
      modelling approach using NONMEM. Oxaliplatin was administered in a 5 % dextrose
      solution (2 L/m(2)) at 360 (n = 58) or 460 mg/m(2) (n = 17). The most frequently
      observed toxicities were related to the peritoneal, systemic exposures and to the
      parameters corresponding to the oxaliplatin absorption from peritoneal cavity
      into plasma. RESULTS: IP (n = 536), UF (n = 669) and B (n = 661) concentrations
      were simultaneously described according to a five-compartment PK model with
      irreversible nonlinear binding from UF to B according to a Michaelis-Menten
      equation. The mean (+/-SD) maximum fraction of dose absorbed and elimination half
      life from the peritoneum was 53.7 % (+/-8.5) and 0.49 h (+/-0.1), respectively.
      The mean (+/-SD) ratio AUC(IP)/AUC(UF) was 5.3 (+/-2) confirming the
      pharmacokinetic advantage of the procedure. Haemoperitoneum (22.7 %), neuropathy
      (18.7 %), grade 3/4 thrombocytopenia (13.3 %) were the most frequently reported
      toxicities. AUC(UF) accounts for approximately 12 % of the variation in the
      maximum percentage of platelet decrease (r = 0.35, p = 0.002). Thrombocytopenia
      was correlated with higher AUCUF, partly dependent on the extent and rate of
      oxaliplatin absorption. CONCLUSIONS: Despite a common dose administered,
      variability in peritoneal and systemic oxaliplatin exposures are observed,
      leading to differences in haematological toxicity between patients.

PMID- 25053387
TI  - No pharmacokinetic alteration of docetaxel following coadministration of
      aprepitant 3 h before docetaxel infusion.
AB  - PURPOSE: Aprepitant, a CYP3A4 substrate, effectively prevents chemotherapy
      induced nausea and vomiting. Oral aprepitant 1 h before intravenous infusion of
      docetaxel does not change the pharmacokinetics of docetaxel. In practical
      combination chemotherapy, oral aprepitant is given 3 h before docetaxel infusion.
      We examined effects of this treatment schedule on the pharmacokinetics of
      docetaxel. METHODS: Inhibition constant (K(i)) of aprepitant for CYP3A-mediated
      docetaxel hydroxylation was estimated with human liver microsomes. A prospective,
      open-label, triple-crossover study was performed in balanced groups of cancer
      patients who received three consecutive cycles of docetaxel, consisting of
      docetaxel alone (A), docetaxel plus aprepitant given 3 h before docetaxel (B1),
      and docetaxel plus aprepitant given 1 h before docetaxel (B2). Three treatment
      arms were studied: Arm I, B1 followed by A and B2, respectively; Arm II, B2
      followed by A and B1, respectively; and Arm III, A followed by B2 and B1,
      respectively. Pharmacokinetics of docetaxel and aprepitant were evaluated on day
      1. RESULTS: The K(i) value was estimated to be 9.82 uM. Eligible patients (20)
      were allocated to Arm I (8), Arm II (7), or Arm III (5). On combined analysis of
      data from all patients assigned to Arms I-III, there were no significant
      differences among cycles A, B1, and B2 in the area under the plasma concentration
      time curve (AUC) of docetaxel or the docetaxel AUC divided by actual dose.
      Pharmacokinetics of aprepitant showed large interindividual variability.
      CONCLUSION: Administration of aprepitant 3 h before docetaxel infusion did not
      alter the pharmacokinetics of docetaxel.

PMID- 25053388
TI  - A phase 1 study to evaluate effect of food on veliparib pharmacokinetics and
      relative bioavailability in subjects with solid tumors.
AB  - PURPOSE: A phase 1 study was conducted to evaluate the bioavailability and food
      effect of a new veliparib formulation in subjects with solid tumors. METHODS:
      Subjects (planned: Stage I, N = 20; Stage II, N = 16) received four regimens of a
      single oral dose of veliparib utilizing a group-sequential design. Subjects were
      administered single doses of 40 mg veliparib supplied as four 10 mg current
      formulation, four 10 mg new formulation and one 40 mg new formulation under
      fasting conditions and under non-fasting conditions. Serial blood samples were
      collected for the determination of veliparib pharmacokinetics. At the end of
      Stage I, the relative bioavailability between each pair of regimens was assessed
      by a two one-sided tests procedure from the analyses of the natural logarithms of
      C(max) and AUC. A 92.7 % confidence interval within the 0.80-1.25 range between
      each regimen pair determined bioequivalence. RESULTS: Four 10 mg current
      formulation capsules, four 10 mg new formulation and one 40 mg new formulation
      were bioequivalent with respect to C(max) and AUC under fasting conditions. The
      administration of a high-fat meal did not have a significant effect on AUC and
      only caused a slight decrease in veliparib C(max) (17 %) and a delay of
      approximately 1 h in T(max). CONCLUSIONS: The 40 mg new capsule was bioequivalent
      to currently used formulation. Food had no effect on the extent of veliparib
      absorption and only a small (17 %) decrease in peak exposure of veliparib.

PMID- 25053389
TI  - Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of navitoclax (ABT
      263) induced thrombocytopenia.
AB  - OBJECTIVE: Navitoclax is a first-in-class, orally bioavailable, targeted Bcl-2
      family protein inhibitor and promotes apoptosis. Thrombocytopenia is a primary
      dose-limiting toxicity of navitoclax which exhibited a distinct time profile in
      circulating platelets from that caused by traditional chemotherapies. A
      population pharmacokinetic/pharmacodynamic (PK/PD) model was developed to
      describe the pharmacokinetic of navitoclax as well as the time course of the
      platelet counts in cancer patients receiving navitoclax. METHODS: Data from 256
      patients who received oral navitoclax (dose range 10-475 mg) as a 14/21-day
      schedule or a continuous once daily (QD) schedule were used to construct the
      model using NONMEM. The PK model was a two-compartmental model with a lag-time
      and a transit compartment in absorption. The PD model was a semi-physiological
      model that comprised a progenitor cell compartment, three transition compartments
      representing the maturation chain in the bone marrow and a peripheral blood
      compartment. Compared with the previously published models, the model established
      in this analysis applied a different feedback mechanism and introduced a new
      concept of progenitor cell "pool", which describes a large pool of platelet
      progenitor cells at the beginning of navitoclax treatment. RESULTS: The PD model
      was able to describe a slight downward trend of platelet counts over the long
      term navitoclax treatment as observed in around 8 % of the patients and the
      initial drop in platelets seen in our Phase 1/2a studies. CONCLUSIONS: We have
      developed a new semi-physiological platelet model for describing fast drop of
      platelets after initial navitoclax administration and long-term decline of
      platelets after continuous administration of navitoclax.

PMID- 25053390
TI  - Should EGFR mutations be tested in advanced lung squamous cell carcinomas to
      guide frontline treatment?
AB  - There is no argument over using epidermal growth factor receptor (EGFR) mutation
      status to guide the frontline treatment for advanced lung adenocarcinoma (LADC);
      however, the role of the testing in lung squamous cell carcinoma (LSQC) remains
      controversial. Currently, the guidelines/consensus statements regarding EGFR
      mutation testing in LSQC are not consistent among different oncology societies.
      American Society of Clinical Oncology recommends performing EGFR mutation testing
      in all patients; European Society for Medical Oncology, College of American
      Pathologists/International Association for the Study of Lung Cancer/Association
      for Molecular Pathology, and National Comprehensive Cancer Network suggest for
      some selected group. EGFR mutation is rarely found in LSQC; however, more
      importantly, it is not a valid predictive biomarker for EGFR tyrosine kinase
      inhibitors (EGFR-TKI) in LSQC as it has been shown in LADC. Available data showed
      that the response rate and progression-free survival in EGFR mutant LSQC patients
      treated with EGFR-TKI are not better than that observed in patients treated with
      platinum-doublet chemotherapy in the first-line setting. Therefore, in contrast
      to advanced LADC, EGFR mutation testing may not be necessarily performed upfront
      in advanced LSQC because not only the mutation rate is low, but also the
      predictive value is insufficient. For LSQC patients with known sensitizing-EGFR
      mutations, both conventional chemotherapy and EGFR-TKI are acceptable frontline
      treatment options. 

PMID- 25053391
TI  - Modulatory effects of meloxicam on cardiotoxicity and antitumor activity of
      doxorubicin in mice.
AB  - PURPOSE: This study was undertaken to assess the possible modulatory effects and
      mechanisms of meloxicam, a cyclooxygenase-2 inhibitor, on the antitumor activity
      and cardiotoxicity of doxorubicin in a mice model of mammary carcinoma. METHODS:
      Solid tumor mass was developed in female albino mice using Ehrlich carcinoma
      cells. Forty mice-bearing tumor were divided randomly into four groups for
      treatment: with saline, meloxicam 10 mg/kg, doxorubicin 5 mg/kg and meloxicam 1 h
      ahead of doxorubicin, twice weekly for 2 weeks. Tumor volume was followed up and
      cardiac protective utility was estimated via measuring heart and serum
      parameters. RESULTS: Meloxicam expressed a non-significant increase in
      doxorubicin antitumor activity. Conversely, meloxicam significantly (p < 0.01)
      mitigated doxorubicin-induced elevation of serum cardiac enzymes [creatine
      kinase, lactate dehydrogenase and troponin-I]; cardiac lipid peroxidations
      marker; cardiac active caspase-3 content; and cardiac prostaglandin E2 content.
      Meloxicam significantly abrogated doxorubicin-induced disturbance in heart
      histology and relative heart weight to body weight. Meloxicam normalized
      doxorubicin-induced suppression in heart antioxidant enzymes activities and gene
      expressions [superoxide dismutase, glutathione peroxidase (GSH-Px) and catalase],
      and heart GSH content. In addition, meloxicam ameliorated doxorubicin-induced
      disturbance in phase II metabolizing enzyme, cardiac quinone reductase (QR), at
      activity level and mRNA expression. CONCLUSION: Meloxicam protects heart against
      doxorubicin toxicity without affecting its antitumor activity against solid
      mammary cancer model in mice. This protective effect is attributed to antioxidant
      effect, antiradical effect, antiinflammatory action, antiapoptotic effect and
      induction of QR enzyme.

PMID- 25053392
TI  - The geographic distribution of onchocerciasis in the 20 participating countries
      of the African Programme for Onchocerciasis Control: (2) pre-control endemicity
      levels and estimated number infected.
AB  - BACKGROUND: The original aim of the African Programme for Onchocerciasis Control
      (APOC) was to control onchocerciasis as a public health problem in 20 African
      countries. In order to identify all high risk areas where ivermectin treatment
      was needed to achieve control, APOC used Rapid Epidemiological Mapping of
      Onchocerciasis (REMO). REMO involved spatial sampling of villages to be surveyed,
      and examination of 30 to 50 adults per village for palpable onchocercal nodules.
      REMO has now been virtually completed and we report the results in two articles.
      A companion article reports the delineation of high risk areas based on expert
      analysis. The present article reports the results of a geostatistical analysis of
      the REMO data to map endemicity levels and estimate the number infected. METHODS:
      A model-based geostatistical analysis of the REMO data was undertaken to generate
      high-resolution maps of the predicted prevalence of nodules and of the
      probability that the true nodule prevalence exceeds the high risk threshold of
      20%. The number infected was estimated by converting nodule prevalence to
      microfilaria prevalence, and multiplying the predicted prevalence for each
      location with local data on population density. The geostatistical analysis
      included the nodule palpation data for 14,473 surveyed villages. RESULTS: The
      generated map of onchocerciasis endemicity levels, as reflected in the prevalence
      of nodules, is a significant advance with many new endemic areas identified. The
      prevalence of nodules was > 20% over an area of 2.5 million km2 with an estimated
      population of 62 million people. The results were consistent with the delineation
      of high risk areas of the expert analysis except for borderline areas where the
      prevalence fluctuated around 20%. It is estimated that 36 million people would
      have been infected in the APOC countries by 2011 if there had been no ivermectin
      treatment. CONCLUSIONS: The map of onchocerciasis endemicity levels has proven
      very valuable for onchocerciasis control in the APOC countries. Following the
      recent shift to onchocerciasis elimination, the map continues to play an
      important role in planning treatment, evaluating impact and predicting treatment
      end dates in relation to local endemicity levels.

PMID- 25053393
TI  - Inactivation of bacteria via photosensitization of vitamin K3 by UV-A light.
AB  - This study investigated inactivation of bacteria with ultraviolet light A
      irradiation in combination with vitamin K3 as a photosensitizer. Six bacteria
      including Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus,
      Staphylococcus epidermidis, Klebsiella pneumoniae, and Escherichia coli suspended
      in vitamin K3 aqueous solution were exposed to ultraviolet light A. Five of six
      bacteria, with the exception of Pseudomonas aeruginosa, were reduced by eight
      logs with 1600 MUM of vitamin K3 and 5.8 J cm(-2) UV-A irradiation. Pseudomonas
      aeruginosa was reduced by four logs under these conditions. Reactive oxygen
      species including singlet oxygen, hydroxyl radical and superoxide anion radical
      were generated in vitamin K3 aqueous solution under UV-A irradiation. These
      results suggest that vitamin K3 and UV-A irradiation may be effective for
      bacterial inactivation in environmental and medical applications.

PMID- 25053394
TI  - Paired Atrial Signals: Explain the Mechanism.

PMID- 25053395
TI  - Novel tetranuclear copper |2 + 4| cubanes resulting from unprecedented C-O bond
      formation cum dearomatization.
AB  - Novel tetranuclear copper |2 + 4| cubanes 1 and 2 have been synthesized from the
      reaction of hydrated copper salts/precursors with N,O chelating beta-ketoaminato
      ligands. Creation of 1 and 2 occurs by in situ generation of the tridentate
      chelating species HL1O(2-) via copper mediated C-O bond formation and
      dearomatization of H3L1, while anhydrous salts afforded mononuclear complex 3.

PMID- 25053396
TI  - Sex differences in the relationship between blood mercury concentration and
      metabolic syndrome risk.
AB  - BACKGROUND: Mercury exposure enhances free radical production and reduces
      activity of anti-oxidant enzymes, resulting in detrimental health effects. Some
      researchers have reported an association between blood mercury and increased risk
      of metabolic syndrome (MetS); however, sex differences in the relationship were
      not fully considered. AIM: To examine the sex differences in the relationship
      between blood mercury concentration and the increased risk of MetS in Korean men
      and women. MATERIALS AND METHODS: A nationwide cross-sectional study was
      conducted to examine the relationship between blood mercury concentration and
      MetS in 2,976 men and 3,074 women over 19 years of age (aged 19-87 years), using
      data from the 2010-2012 Korean National Health and Nutrition Examination Survey
      (KNHANES-V). Multiple logistic regression analysis was used to assess the
      relationship between blood mercury concentration and the prevalence risk of MetS
      after adjusting for confounding variables. RESULTS: Compared to the lowest
      quartile of blood mercury concentration, the OR (95 % CI) for MetS of the highest
      quartile in men was 1.62 (1.15-2.28) after adjusting for age, smoking status,
      alcohol consumption, regular exercise, and BMI. Similarly, in multiple logistic
      regression analysis using log2-transformed blood mercury as a continuous
      variable, the OR (95 % CI) for having MetS with doubling of blood mercury was
      1.20 (1.05-1.36) after adjusting for the same co-variables. However, the
      relationship was not observed in women after adjusting for the same co-variables.
      CONCLUSIONS: Blood mercury concentration was independently associated with an
      increased risk of MetS in men.

PMID- 25053397
TI  - Solvent-tolerance of fungi located on an interface between an agar plate and an
      organic solvent.
AB  - While 6 by 20 of type culture fungi could grow on an interface between organic
      solvent (log P, 4.12) and agar plate, 13 by 20 of strains could form a large
      colony after the removal of more toxic solvent, such as styrene (log P, 2.95) and
      tert-butyl acetate (log P, 1.76) because of viability of spores on the interface.

PMID- 25053398
TI  - Frequency of HLA-A alleles in the Syrian population genotyped by sequence-based
      typing.
AB  - HLA-A molecules are highly polymorphic. Their accurate typing at a high
      resolution level is crucial for successful organ, bone marrow and cord blood
      transplantation. Furthermore, several HLA alleles have been involved in
      susceptibility to autoimmune diseases, allergies, cancers and inflammations. In
      order to determine common HLA-A alleles in Syria and their frequencies, sequence
      based typing (SBT) was used to genotype HLA-A alleles at high resolution (four
      digit level) among one hundred and thirty randomly selected Syrian individuals.
      Exons 2, 3 and 4 of the HLA-A gene were amplified by PCR and sequenced. The sbt
      engine software was used for allele assignment. Ambiguities were solved using
      group-specific sequencing primers (GSSPs). We could identify 32 different HLA-A
      alleles which were divided into 3 groups: high frequency (approximately 10%,
      A*01:01; A*24:02; A*03:01; A*02:01), moderate frequency (approximately 3%, such
      as A*02:05, A*31:01 and A*33:01), and low frequency (approximately 1%, such as
      A*02:11, A*29:01, A*02:02 and A*36:01). Homozygosity rate was higher than
      expected (11.5% vs. 7.15%). For high frequency alleles, our results show
      similarity to neighbouring countries. However, 15 alleles (such as A*02:04,
      A*02:06, A*02:11 and A*02:17) found in our cohort in low frequencies were never
      reported in some or all neighbouring countries. This is the first report on HLA-A
      allele frequencies in Syria. In spite of the relatively low number of tested
      subjects, our results revealed a high degree of diversity, with 32 different
      alleles, reflecting the high ethnic heterogeneity of the Syrian population. The
      identification of alleles rarely or never reported in neighbouring countries
      indicates a higher genetic diversity in Syria. 

PMID- 25053399
TI  - Concomitant sensitization to ragweed and mugwort pollen: who is who in clinical
      allergy?
AB  - BACKGROUND: In many areas of Europe, double sensitization to ragweed and mugwort
      is common, and because of the overlapping flowering periods of the 2 plants, it
      is not possible to diagnose the primary sensitizing allergen source and hence to
      determine the proper immunotherapy. OBJECTIVES: To elucidate whether double
      sensitized patients are cosensitized or cross-sensitized and, in the latter case,
      to define the primary sensitizer. METHODS: Serum samples from 34 patients with
      late summer respiratory allergy underwent skin prick testing with whole ragweed,
      and mugwort extracts were analyzed for their reactivity to recombinant Art v 1
      and Amb a 1 by ImmunoCAP and then to Amb a 1, Art v 6, and Art v 1 isoforms by a
      proteomic approach. In double reactors, the primary sensitizing sources were
      detected by inhibition experiments. RESULTS: Serum samples from patients
      monosensitized to ragweed contained IgE to epitopes specific of all Amb a 1
      isoforms. In contrast, serum samples from double reactors found to be primarily
      sensitized to mugwort reacted to Art v 1 and Art v 6 and cross-reacted to a few
      Amb a 1 isoforms. Finally, serum samples from double reactors found to be
      primarily sensitized to ragweed contained IgE reacting to all Amb a 1 isoforms,
      part of which cross-reacted to Art v 6. We did not find cosensitized patients.
      CONCLUSION: This study found that Art v 6 plays an important role in mugwort
      allergy and that the cross-reactivity between Art v 6 and Amb a 1 is frequent,
      bidirectional, and clinically relevant in the area of Milan.

PMID- 25053400
TI  - Factors related to histamine concentrations for positive control in prick
      puncture skin testing.

PMID- 25053402
TI  - Selective inhibition of sphingosine kinase-1 protects adipose tissue against LPS
      induced inflammatory response in Zucker diabetic fatty rats.
AB  - Obesity is associated with a state of chronic inflammation. The chemokine (C-C
      motif) ligand 5 (CCL5) has been proposed to modulate the inflammatory response in
      adipose tissue (AT). However, the mechanisms underlying CCL5 upregulation in AT
      remain undefined. The objective of the present study was to evaluate whether the
      enzyme sphingosine kinase-1 (SK1) would modulate the expression of CCL5 and other
      inflammatory biomarkers in primary adipocytes and its potential role in
      lipopolysaccharide (LPS)-induced AT inflammation in a rat model of diabetes. To
      address this, LPS-stimulated primary adipocytes and 3T3-L1 cells were treated
      with a SK inhibitor, and the expression of Ccl5 and other CC chemokines were
      studied. Moreover, the effect of SK1 knockdown on cytokine production was
      analyzed in 3T3-L1 cells by transfection of SK1-specific small-interfering RNA
      (siRNA). The anti-inflammatory effects of SK inhibitor in AT were also
      investigated in vivo using the Zucker lean normoglycemic control (ZLC) rats. LPS
      treatment stimulated Ccl5, IL-6, pentraxin 3 (Ptx3), and Tnfalpha mRNA expression
      in primary adipocytes and 3T3-L1 cells, whereas pharmacologically and siRNA
      mediated SK1 inhibition strongly reduced mRNA levels of proinflammatory cytokines
      in these cells. Similarly, administration of SK inhibitor to ZLC rats prevented
      the LPS-induced inflammatory response in AT. Our data demonstrate a role for SK1
      in endotoxin-induced cytokine expression in adipocytes and suggest that
      inhibition of SK1 may be a potential therapeutic tool in the prevention and
      treatment of chronic and common metabolic disorders, including obesity, insulin
      resistance, and type 2 diabetes. 

PMID- 25053401
TI  - FGF23 directly impairs endothelium-dependent vasorelaxation by increasing
      superoxide levels and reducing nitric oxide bioavailability.
AB  - Fibroblast growth factor 23 (FGF23) is secreted primarily by osteocytes and
      regulates phosphate and vitamin D metabolism. Elevated levels of FGF23 are
      clinically associated with endothelial dysfunction and arterial stiffness in
      chronic kidney disease (CKD) patients; however, the direct effects of FGF23 on
      endothelial function are unknown. We hypothesized that FGF23 directly impairs
      endothelial vasorelaxation by hindering nitric oxide (NO) bioavailability. We
      detected expression of all four subtypes of FGF receptors (Fgfr1-4) in male mouse
      aortas. Exogenous FGF23 (90-9,000 pg/ml) did not induce contraction of aortic
      rings and did not relax rings precontracted with PGF2alpha. However,
      preincubation with FGF23 (9,000 pg/ml) caused a ~36% inhibition of endothelium
      dependent relaxation elicited by acetylcholine (ACh) in precontracted aortic
      rings, which was prevented by the FGFR antagonist PD166866 (50 nM). Furthermore,
      in FGF23-pretreated (9,000 pg/ml) aortic rings, we found reductions in NO levels.
      We also investigated an animal model of CKD (Col4a3(-/-) mice) that displays
      highly elevated serum FGF23 levels and found they had impaired endothelium
      dependent vascular relaxation and reduced nitrate production compared with age
      matched wild types. To elucidate a mechanism for the FGF23-induced impairment, we
      measured superoxide levels in endothelial cells and aortic rings and found that
      they were increased following FGF23 treatment. Crucially, treatment with the
      superoxide scavenger tiron reduced superoxide levels and also restored aortic
      relaxation to ACh. Therefore, our data suggest that FGF23 increases superoxide,
      inhibits NO bioavailability, and causes endothelial dysfunction in mouse aorta.
      Together, these data provide evidence that high levels of FGF23 contribute to
      cardiovascular dysfunction. 

PMID- 25053403
TI  - DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone
      strength in male diabetic rats.
AB  - Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing
      dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in
      type 2 diabetes patients. DPP IV substrates not only increase insulin secretion
      but also affect bone metabolism. In this study, the effect of DPP IV inhibitor
      sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic
      rats. This study included 64 male Wistar rats divided into four groups (n = 16):
      two diabetic and two control groups. One diabetic and one control group received
      sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in
      vivo MUCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric
      analysis of bone parameters. The mechanical resistance of femora to fracture was
      assessed using a three-point bending test, and serum levels of bone metabolic
      markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin
      treated groups. Trabecular bone loss, the decrease in trabecular number, and the
      increase in trabecular spacing was attenuated through sitagliptin treatment in
      diabetic rats, as shown by in vivo MUCT. Bone histomorphometry was in line with
      these results. MUCT analysis furthermore showed that sitagliptin prevented
      cortical bone growth stagnation in diabetic rats, resulting in stronger femora
      during three-point bending. Finally, the serum levels of the resorption marker
      CTX-I were significantly lower in sitagliptin-treated diabetic animals compared
      with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates
      bone loss and increases bone strength in diabetic rats probably through the
      reduction of bone resorption and independent of glycemic management. 

PMID- 25053404
TI  - Birthweight, early life body size and adult mammographic density: a review of
      epidemiologic studies.
AB  - PURPOSE: To evaluate the association between birth weight and early life body
      size with adult mammographic density in the peer-reviewed literature. METHODS: A
      comprehensive literature search was conducted through January, 2014. English
      language articles that assessed adult mammographic density (MD) in relation to
      early life body size (<=18 years old), or birthweight were included. RESULTS:
      Nine studies reported results for early life body size and %MD. Both exposure and
      outcome were assessed at different ages using multiple methods. In premenopausal
      women, findings were inconsistent; two studies reported significant, inverse
      associations, one reported a non-significant, inverse association, and two
      observed no association. Reasons for these inconsistencies were not obvious. In
      postmenopausal women, four of five studies supported an inverse association. Two
      of three studies that adjusted for menopausal status found significant, inverse
      associations. Birthweight and %MD was evaluated in nine studies. No association
      was seen in premenopausal women and two of three studies reported positive
      associations in postmenopausal women. Three of four studies that adjusted for
      menopausal status found no association. DISCUSSION: Early life body size and
      birthweight appear unrelated to %MD in premenopausal women while an inverse
      association in postmenopausal women is more likely. Although based on limited
      data, birthweight and %MD appear positively associated in postmenopausal women.
      Given the small number of studies, the multiple methods of data collection and
      analysis, other methodologic issues, and lack of consistency in results,
      additional research is needed to clarify this complex association and develop a
      better understanding of the underlying biologic mechanisms.

PMID- 25053405
TI  - Associations of change in television viewing time with biomarkers of
      postmenopausal breast cancer risk: the Australian Diabetes, Obesity and Lifestyle
      Study.
AB  - PURPOSE: Sedentary behavior has been previously shown, in a cross-sectional
      study, to have deleterious associations with biomarkers of postmenopausal breast
      cancer risk. We examined the associations of change in sedentary behavior [daily
      television (TV) viewing time, h/day] over a 5-year period with putative markers
      of postmenopausal breast cancer risk. METHODS: The analytic cohort consisted of
      1,001 postmenopausal women from the Australian Diabetes, Obesity and Lifestyle
      (AusDiab) study (1999-2005). Multivariate linear regression models were used to
      examine associations of change in TV viewing time with biomarkers of the
      following risk mechanisms: adiposity (body mass index [BMI], waist
      circumference); metabolic dysfunction (fasting plasma glucose, 2-h plasma
      glucose, fasting insulin, insulin resistance [homeostasis model assessment of
      insulin resistance (HOMA-IR)]); and inflammation (high-sensitivity C-reactive
      protein (hs-CRP)). All analyses were adjusted for age, baseline TV viewing, and
      potential confounders. RESULTS: Hourly increments of change in TV viewing time
      were positively associated with BMI (beta = 0.50, 95% CI 0.20, 0.81; p = 0.001),
      waist circumference (beta = 1.18, 95% CI 0.49, 1.87; p = 0.001), fasting insulin
      (beta = 38.13%, 95% CI 37.08, 39.20; p = 0.01) and HOMA-IR (beta = 37.93%, 95% CI
      36.92, 38.98; p = 0.03) in fully adjusted models. Significant associations with
      BMI, waist circumference, fasting insulin and HOMA-IR were also present in
      analyses using categories of change in TV viewing time (reduced, same,
      increased). CONCLUSIONS: The findings suggest that increasing habitual sedentary
      behavior over time could increase breast cancer risk among postmenopausal women.
      Further investigation into the role of sedentary behavior in breast cancer
      etiology is warranted.

PMID- 25053406
TI  - Mortality from lymphohematopoietic neoplasms and other causes in a cohort of
      laminated plastic workers exposed to formaldehyde.
AB  - PURPOSE: A possible relationship between exposure to formaldehyde and leukemia
      particularly myeloid leukemia-as well as of lymphoid neoplasms has been debated
      and is still controversial. We thus examined the issue using data from a cohort
      of workers of a laminated plastic factory sited in Piedmont, northern Italy.
      METHODS: The study cohort included 2,750 subjects (2,227 men and 523 women) who
      worked in the factory between 1947 and 2011, for at least 180 days. Follow-up
      ended in May 2011, for a total of 70,933 person-years of observation. We computed
      standardized mortality ratios (SMR) and 95% confidence intervals (CI) using
      national and (whenever available) Piedmont Region death rates. RESULTS: Overall,
      there were 417 deaths versus 493.4 expected ones (SMR = 84.5, 95% CI 76.6-93.0).
      The SMRs were 79.8 (95% CI 67.5-93.6) for total cancer mortality, 148.5 (95% CI
      68.0-282.2) for oral cavity and pharynx (three deaths were registered, but not
      confirmed, as nasopharyngeal cancer), 48.3 (95% CI 13.1-123.7) for pancreas, 66.1
      (95% CI 13.6-193.0) for larynx, and 96.7 (95% CI 72.0-127.2) for lung cancer. The
      SMR of all lymphohematopoietic malignancies was 68.6 (95% CI 31.4-130.3; nine
      observed deaths). This tended to increase with duration of exposure and to
      decrease with period at first exposure, always remaining below 100. There were
      four deaths from lymphoma (SMR = 74.1, 95% CI 20.1-189.6) and five deaths from
      leukemia (SMR = 92.4, 95% CI 29.9-215.3). CONCLUSIONS: We found no meaningful
      excess mortality from any lymphohematopoietic nor other neoplasms, except
      possibly for nasopharyngeal cancer.

PMID- 25053407
TI  - C-reactive protein, interleukin-6 and the risk of colorectal cancer: a meta
      analysis.
AB  - PURPOSE: Many studies have evaluated the associations between pre-diagnostic
      circulating C-reactive protein (CRP), interleukin-6 (IL-6) and colorectal cancer
      risk, but their results are inconsistent. We therefore conducted a meta-analysis
      to investigate these associations. METHODS: A comprehensive literature search up
      to October 2013 was undertaken in PubMed. Pooled relative risk (RR) estimates and
      95% confidence intervals (CIs) were used to calculate estimated effect. RESULTS:
      Eighteen studies on CRP comprising a total of 4,706 colorectal cancer cases were
      included in this meta-analysis. The summary RR of colorectal cancer for one unit
      change in natural logarithm (ln) CRP was 1.12 [95% CI (1.05-1.21)]. There was
      statistically significant heterogeneity among studies (p = 0.006; I (2) = 51.7%).
      After excluding the studies contributing most to the heterogeneity, summary
      estimate was essentially unchanged. In addition, the association was significant
      for colon cancer [RR = 1.13, 95 % CI (1.05-1.21)], not for rectal cancer [RR =
      1.03, 95% CI (0.90-1.17)]. We also found that CRP was significantly associated
      with increased risk of colorectal cancer among men, but not among women. There
      were six studies on IL-6 that involved a total of 1,068 colorectal cancer cases.
      The pooled RR of colorectal cancer for one unit change in ln IL-6 was 1.10 (95%
      CI 0.88-1.36), and no statistically significant heterogeneity was found (p =
      0.175; I(2) = 34.8%). CONCLUSION: Our results suggest that pre-diagnostic
      circulating CRP is associated with increased risk of colorectal cancer. However,
      there is no significant association between IL-6 and colorectal cancer risk.

PMID- 25053408
TI  - Substituted cysteine accessibility reveals a novel transmembrane 2-3 reentrant
      loop and functional role for transmembrane domain 2 in the human proton-coupled
      folate transporter.
AB  - The proton-coupled folate transporter (PCFT) is a folate-proton symporter highly
      expressed in solid tumors that can selectively target cytotoxic antifolates to
      tumors under acidic microenvironment conditions. Predicted topology models for
      PCFT suggest that the loop domain between transmembrane domains (TMDs) 2 and 3
      resides in the cytosol. Mutations involving Asp-109 or Arg-113 in the TMD2-3 loop
      result in loss of activity. By structural homology to other solute carriers, TMD2
      may form part of the PCFT substrate binding domain. In this study we mutated the
      seven cysteine (Cys) residues of human PCFT to serine, creating Cys-less PCFT.
      Thirty-three single-Cys mutants spanning TMD2 and the TMD2-3 loop in a Cys-less
      PCFT background were transfected into PCFT-null HeLa cells. All 33 mutants were
      detected by Western blotting, and 28 were active for [(3)H]methotrexate uptake at
      pH 5.5. For the active residues, we performed pulldown assays with membrane
      impermeable 2-aminoethyl methanethiosulfonate-biotin and streptavidin beads to
      determine their aqueous-accessibilities. Multiple residues in TMD2 and the TMD2-3
      loop domain reacted with 2-aminoethyl methanethiosulfonate-biotin, establishing
      aqueous accessibilities. Pemetrexed pretreatment inhibited biotinylation of TMD2
      mutants G93C and F94C, and biotinylation of these residues inhibited methotrexate
      transport activity. Our results suggest that the TMD 2-3 loop domain is aqueous
      accessible and forms a novel reentrant loop structure. Residues in TMD2 form an
      aqueous transmembrane pathway for folate substrates, and Gly-93 and Phe-94 may
      contribute to a substrate binding domain. Characterization of PCFT structure is
      essential to understanding the transport mechanism including the critical
      determinants of substrate binding. 

PMID- 25053409
TI  - Ligands for FKBP12 increase Ca2+ influx and protein synthesis to improve skeletal
      muscle function.
AB  - Rapamycin at high doses (2-10 mg/kg body weight) inhibits mammalian target of
      rapamycin complex 1 (mTORC1) and protein synthesis in mice. In contrast, low
      doses of rapamycin (10 MUg/kg) increase mTORC1 activity and protein synthesis in
      skeletal muscle. Similar changes are found with SLF (synthetic ligand for FKBP12,
      which does not inhibit mTORC1) and in mice with a skeletal muscle-specific FKBP12
      deficiency. These interventions also increase Ca(2+) influx to enhance refilling
      of sarcoplasmic reticulum Ca(2+) stores, slow muscle fatigue, and increase
      running endurance without negatively impacting cardiac function. FKBP12
      deficiency or longer treatments with low dose rapamycin or SLF increase the
      percentage of type I fibers, further adding to fatigue resistance. We demonstrate
      that FKBP12 and its ligands impact multiple aspects of muscle function. 

PMID- 25053410
TI  - The balanced regulation of Hsc70 by DNJ-13 and UNC-23 is required for muscle
      functionality.
AB  - The molecular chaperone Hsc70 assists in the folding of non-native proteins
      together with its J domain- and BAG domain-containing cofactors. In
      Caenorhabditis elegans, two BAG domain-containing proteins can be identified, one
      of them being UNC-23, whose mutation induces severe motility dysfunctions. Using
      reporter strains, we find that the full-length UNC-23, in contrast to C-terminal
      fragments, localizes specifically to the muscular attachment sites. C-terminal
      fragments of UNC-23 instead perform all Hsc70-related functions, like ATPase
      stimulation and regulation of folding activity, albeit with lower affinity than
      BAG-1. Interestingly, overexpression of CFP-Hsc70 can induce muscular defects in
      wild-type nematodes that phenocopy the knockout of its cofactor UNC-23.
      Strikingly, the motility dysfunction in the unc-23 mutated strain can be cured
      specifically by down-regulation of the antagonistic Hsc70 cochaperone DNJ-13,
      implying that the severe phenotype is caused by misregulation of the Hsc70 cycle.
      These findings point out that the balanced action of cofactors in the ATP-driven
      cycle of Hsc70 is crucial for the contribution of Hsc70 to muscle functionality. 

PMID- 25053411
TI  - Retrotransposition of long interspersed element 1 induced by methamphetamine or
      cocaine.
AB  - Long interspersed element 1 (L1) is a retroelement constituting ~17% of the human
      genome. A single human cell has 80-100 copies of L1 capable of retrotransposition
      (L1-RTP), ~10% of which are "hot L1" copies, meaning they are primed for
      "jumping" within the genome. Recent studies demonstrated induction of L1 activity
      by drugs of abuse or low molecular weight compounds, but little is known about
      the underlying mechanism. The aim of this study was to identify the mechanism and
      effects of methamphetamine (METH) and cocaine on L1-RTP. Our results revealed
      that METH and cocaine induced L1-RTP in neuronal cell lines. This effect was
      found to be reverse transcriptase-dependent. However, METH and cocaine did not
      induce double-strand breaks. RNA interference experiments combined with add-back
      of siRNA-resistant cDNAs revealed that the induction of L1-RTP by METH or cocaine
      depends on the activation of cAMP response element-binding protein (CREB). METH
      or cocaine recruited the L1-encoded open reading frame 1 (ORF1) to chromatin in a
      CREB-dependent manner. These data suggest that the cellular cascades underlying
      METH- and cocaine-induced L1-RTP are different from those behind L1-RTP triggered
      by DNA damage; CREB is involved in drug-induced L1-RTP. L1-RTP caused by drugs of
      abuse is a novel type of genomic instability, and analysis of this phenomenon
      might be a novel approach to studying substance-use disorders. 

PMID- 25053412
TI  - Agonist ligands mediate the transcriptional response of nuclear receptor
      heterodimers through distinct stoichiometric assemblies with coactivators.
AB  - The constitutive androstane (CAR) and retinoid X receptors (RXR) are ligand
      mediated transcription factors of the nuclear receptor protein superfamily.
      Functional CAR:RXR heterodimers recruit coactivator proteins, such as the steroid
      receptor coactivator-1 (SRC1). Here, we show that agonist ligands can potentiate
      transactivation through both coactivator binding sites on CAR:RXR, which
      distinctly bind two SRC1 molecules. We also observe that SRC1 transitions from a
      structurally plastic to a compact form upon binding CAR:RXR. Using small angle x
      ray scattering (SAXS) we show that the CAR(tcp):RXR(9c).SRC1 complex can
      encompass two SRC1 molecules compared with the CAR(tcp):RXR.SRC1, which binds
      only a single SRC1. Moreover, sedimentation coefficients and molecular weights
      determined by analytical ultracentrifugation confirm the SAXS model. Cell-based
      transcription assays show that disrupting the SRC1 binding site on RXR alters the
      transactivation by CAR:RXR. These data suggest a broader role for RXR within
      heterodimers, whereas offering multiple strategies for the assembly of the
      transcription complex. 

PMID- 25053413
TI  - Chemically modified N-acylated hyaluronan fragments modulate proinflammatory
      cytokine production by stimulated human macrophages.
AB  - Low molecular mass hyaluronans are known to induce inflammation. To determine the
      role of the acetyl groups of low molecular mass hyaluronan in stimulating the
      production of proinflammatory cytokines, partial N-deacetylation was carried out
      by hydrazinolysis. This resulted in 19.7 +/- 3.5% free NH2 functional groups,
      which were then acylated by reacting with an acyl anhydride, including acetic
      anhydride. Hydrazinolysis resulted in bond cleavage of the hyaluronan chain
      causing a reduction of the molecular mass to 30-214 kDa. The total NH2 and N
      acetyl moieties in the reacetylated hyaluronan were 0% and 98.7 +/- 1.5%
      respectively, whereas for butyrylated hyaluronan, the total NH2, N-acetyl, and N
      butyryl moieties were 0, 82.2 +/- 4.6, and 22.7 +/- 3.8%, respectively, based on
      (1)H NMR. We studied the effect of these polymers on cytokine production by
      cultured human macrophages (THP-1 cells). The reacetylated hyaluronan stimulated
      proinflammatory cytokine production to levels similar to LPS, whereas partially
      deacetylated hyaluronan had no stimulatory effect, indicating the critical role
      of the N-acetyl groups in the stimulation of proinflammatory cytokine production.
      Butyrylated hyaluronan significantly reduced the stimulatory effect on cytokine
      production by the reacetylated hyaluronan or LPS but had no stimulatory effect of
      its own. The other partially N-acylated hyaluronan derivatives tested showed
      smaller stimulatory effects than reacetylated hyaluronan. Antibody and antagonist
      experiments suggest that the acetylated and partially butyrylated lower molecular
      mass hyaluronans exert their effects through the TLR-4 receptor system.
      Selectively N-butyrylated lower molecular mass hyaluronan shows promise as an
      example of a novel semisynthetic anti-inflammatory molecule. 

PMID- 25053414
TI  - Cysteines introduced into extracellular loops 1 and 4 of human P-glycoprotein
      that are close only in the open conformation spontaneously form a disulfide bond
      that inhibits drug efflux and ATPase activity.
AB  - P-glycoprotein (P-gp) is an ATP-binding cassette drug pump that protects us from
      toxic compounds and confers multidrug resistance. The protein is organized into
      two halves. The halves contain a transmembrane domain (TMD) with six
      transmembrane segments and a nucleotide-binding domain (NBD). The drug- and ATP
      binding sites reside at the TMD1/TMD2 and NBD1/NBD2 interfaces, respectively. ATP
      dependent drug efflux involves changes between the open inward-facing (NBDs
      apart, extracellular loops (ECLs) close together) and the closed outward-facing
      (NBDs close together, ECLs apart) conformations. It is controversial, however,
      whether the open conformation only exists transiently in intact cells because of
      the presence of high levels of ATP. To test for the presence of an open
      conformation in intact cells, reporter cysteines were placed in extracellular
      loops 1 (A80C, N half) and 4 (R741C, C half). The rationale was that cysteines
      A80C/R741C would only come close enough to form a disulfide bond in an open
      conformation (6.9 A apart) because they are separated widely (30.4 A apart) in
      the closed conformation. It was observed that the mutant A80C/R741C cross-linked
      spontaneously (>90%) when expressed in cells. In contrast to previous reports
      showing that trapping P-gp in a closed conformation highly activated ATPase
      activity, here we show that A80C/R741C cross-linking inhibited ATPase activity
      and drug efflux. Both activities were restored when the cross-linked mutant was
      treated with a thiol-reducing agent. The results show that an open conformation
      can be readily detected in cells and that cross-linking of cysteines placed in
      ECLs 1 and 4 inhibits activity. 

PMID- 25053415
TI  - c-Myc programs fatty acid metabolism and dictates acetyl-CoA abundance and fate.
AB  - myc(-/-) rat fibroblasts (KO cells) differ from myc(+/+) (WT) cells and KO cells
      with enforced Myc re-expression (KO-Myc cells) with respect to mitochondrial
      structure and function, utilization of glucose and glutamine as energy-generating
      substrates, and ATP levels. Specifically, KO cells demonstrate low levels of
      glycolysis and oxidative phosphorylation, dysfunctional mitochondria and electron
      transport chain complexes, and depleted ATP stores. We examined here how these
      cells adapt to their energy-deficient state and how they differ in their uptake
      and utilization of long- and medium-chain fatty acids such as palmitate and
      octanoate, respectively. Metabolic tracing of these molecules showed that KO
      cells preferentially utilize them as beta-oxidation substrates and that, rather
      than directing them into phospholipids, preferentially store them as neutral
      lipids. KO cell transcriptional profiling and functional assays revealed a
      generalized up-regulation of pathways involved in fatty acid transport and
      catabolism as well as evidence that these cells attempt to direct acetyl-CoA into
      the tricarboxylic acid (TCA) cycle for ATP production rather than utilizing it
      for anabolic purposes. Additional evidence to support this idea included the
      finding that AMP-dependent protein kinase was constitutively activated in KO
      cells. The complex control of pyruvate dehydrogenase, which links glycolysis to
      the TCA cycle, was also maximized to ensure the conversion of pyruvate to acetyl
      CoA. Despite these efforts to maximize acetyl-CoA for energy-generating purposes,
      its levels remained chronically low in KO cells. This suggests that tumor cells
      with Myc deregulation might be susceptible to novel therapies that limit acetyl
      CoA availability. 

PMID- 25053416
TI  - Heparan sulfate regulates hair follicle and sebaceous gland morphogenesis and
      homeostasis.
AB  - Hair follicle (HF) morphogenesis and cycling are a result of intricate autonomous
      epithelial-mesenchymal interactions. Once the first HF cycle is complete it
      repeatedly undergoes cyclic transformations. Heparan sulfate (HS) proteoglycans
      are found on the cell surface and in the extracellular matrix where they
      influence a variety of biological processes by interacting with physiologically
      important proteins, such as growth factors. Inhibition of heparanase (an HS
      endoglycosidase) in in vitro cultured HFs has been shown to induce a catagen-like
      process. Therefore, this study aimed to elucidate the precise role of HS in HF
      morphogenesis and cycling. An inducible tetratransgenic mouse model was generated
      to excise exostosin glycosyltransferase 1 (Ext1) in keratin 14-positive cells
      from P21. Interestingly, EXT1(StEpiDelta/StEpiDelta) mice presented solely anagen
      HFs. Moreover, waxing the fur to synchronize the HFs revealed accelerated hair
      regrowth in the EXT1(StEpiDelta/StEpiDelta) mice and hindered cycling into
      catagen. The ablation of HS in the interfollicular epidermal cells of mature skin
      led to the spontaneous formation of new HFs and an increase in Sonic Hedgehog
      expression resembling wild-type mice at P0, thereby indicating that the HS/Sonic
      Hedgehog signaling pathway regulates HF formation during embryogenesis and
      prevents HF formation in mature skin. Finally, the knock-out of HS also led to
      the morphogenesis and hyperplasia of sebaceous glands and sweat glands in mature
      mice, leading to exacerbated sebum production and accumulation on the skin
      surface. Therefore, our findings clearly show that an intricate control of HS
      levels is required for HF, sebaceous gland, and sweat gland morphogenesis and HF
      cycling. 

PMID- 25053417
TI  - The molecular mechanism of Shiga toxin Stx2e neutralization by a single-domain
      antibody targeting the cell receptor-binding domain.
AB  - Shiga toxin Stx2e is the major known agent that causes edema disease in newly
      weaned pigs. This severe disease is characterized by neurological disorders,
      hemorrhagic lesions, and frequent fatal outcomes. Stx2e consists of an
      enzymatically active A subunit and five B subunits that bind to a specific
      glycolipid receptor on host cells. It is evident that antibodies binding to the A
      subunit or the B subunits of Shiga toxin variants may have the capability to
      inhibit their cytotoxicity. Here, we report the discovery and characterization of
      a VHH single domain antibody (nanobody) isolated from a llama phage display
      library that confers potent neutralizing capacity against Stx2e toxin. We further
      present the crystal structure of the complex formed between the nanobody
      (NbStx2e1) and the Stx2e toxoid, determined at 2.8 A resolution. Structural
      analysis revealed that for each B subunit of Stx2e, one NbStx2e1 is interacting
      in a head-to-head orientation and directly competing with the glycolipid receptor
      binding site on the surface of the B subunit. The neutralizing NbStx2e1 can in
      the future be used to prevent or treat edema disease. 

PMID- 25053418
TI  - Glucose directly promotes antifungal resistance in the fungal pathogen, Candida
      spp.
AB  - Effects of glucose on the susceptibility of antifungal agents were investigated
      against Candida spp. Increasing the concentration of glucose decreased the
      activity of antifungal agents; voriconazole was the most affected drugs followed
      by amphotericin B. No significant change has been observed for anidulafungin.
      Biophysical interactions between antifungal agents with glucose molecules were
      investigated using isothermal titration calorimetry, Fourier transform infrared,
      and (1)H NMR. Glucose has a higher affinity to bind with voriconazole by hydrogen
      bonding and decrease the susceptibility of antifungal agents during chemotherapy.
      In addition to confirming the results observed in vitro, theoretical docking
      studies demonstrated that voriconazole presented three important hydrogen bonds
      and amphotericin B presented two hydrogen bonds that stabilized the glucose. In
      vivo results also suggest that the physiologically relevant higher glucose level
      in the bloodstream of diabetes mellitus mice might interact with the available
      selective agents during antifungal therapy, thus decreasing glucose activity by
      complex formation. Thus, proper selection of drugs for diabetes mellitus patients
      is important to control infectious diseases. 

PMID- 25053419
TI  - GSK3 protein positively regulates type I insulin-like growth factor receptor
      through forkhead transcription factors FOXO1/3/4.
AB  - Glycogen synthase kinase-3 (GSK3) has either tumor-suppressive roles or pro-tumor
      roles in different types of human tumors. A number of GSK3 targets in diverse
      signaling pathways have been uncovered, such as tuberous sclerosis complex
      subunit 2 and beta-catenin. The O subfamily of forkhead/winged helix
      transcription factors (FOXO) is known as tumor suppressors that induce apoptosis.
      In this study, we find that FOXO binds to type I insulin-like growth factor
      receptor (IGF-IR) promoter and stimulates its transcription. GSK3 positively
      regulates the transactivation activity of FOXO and stimulates IGF-IR expression.
      Although kinase-dead GSK3beta cannot up-regulate IGF-IR, the constitutively
      active GSK3beta induces IGF-IR expression in a FOXO-dependent manner. Serum
      starvation or Akt inhibition leads to an increase in IGF-IR expression, which
      could be blunted by GSK3 inhibition. GSK3beta knockdown or GSK3 inhibitor
      suppresses IGF-I-induced IGF-IR, Akt, and ERK1/2 phosphorylation. Moreover,
      knockdown of GSK3beta or FOXO1/3/4 leads to a decrease in cellular proliferation
      and abrogates IGF-I-induced hepatoma cell proliferation. These results suggest
      that GSK3 and FOXO may positively regulate IGF-I signaling and hepatoma cell
      proliferation. 

PMID- 25053420
TI  - Severe events in the first 6 months of life in a cohort of HIV-unexposed infants
      from South Africa: effects of low birthweight and breastfeeding status.
AB  - OBJECTIVE: To report on risk factors for severe events (hospitalisation or infant
      death) within the first half of infancy amongst HIV-unexposed infants in South
      Africa. METHODS: South African data from the multisite community-based cluster
      randomised trial PROMISE EBF promoting exclusive breastfeeding in three sub
      Saharan countries from 2006 to 2008 were used. The South African sites were Paarl
      in the Western Cape Province, and Umlazi and Rietvlei in KwaZulu-Natal. This
      analysis included 964 HIV-negative mother-infant pairs. Data on severe events and
      infant feeding practices were collected at 3, 6, 12 and 24 weeks post-partum. We
      used a stratified extended Cox model to examine the association between the time
      to the severe event and covariates including birthweight, with breastfeeding
      status as a time-dependent covariate. RESULTS: Seventy infants (7%) experienced a
      severe event. The median age at first hospitalisation was 8 weeks, and the two
      main reasons for hospitalisation were cough and difficult breathing followed by
      diarrhoea. Stopping breastfeeding before 6 months (HR 2.4; 95% CI 1.2-5.1) and
      low birthweight (HR 2.4; 95% CI 1.3-4.3) were found to increase the risk of a
      severe event, whilst maternal completion of high school education was protective
      (HR 0.3; 95% CI 0.1-0.7). CONCLUSIONS: A strengthened primary healthcare system
      incorporating promotion of breastfeeding and appropriate caring practices for low
      birthweight infants (such as kangaroo mother care) are critical. Given the
      leading reasons for hospitalisation, early administration of oral rehydration
      therapy and treatment of suspected pneumonia are key interventions needed to
      prevent hospitalisation in young infants.

PMID- 25053421
TI  - Lightning deaths: a retrospective review of New Mexico's cases, 1977-2009.
AB  - To better understand lightning deaths, a retrospective review of electronic
      records from New Mexico's Office of the Medical Investigator database was
      performed between 1977 and 2009 to update and assess current risk factors.
      Information on demographics, circumstances, autopsy, and death certificates were
      collected and analyzed. Fifty-four decedents were identified, ages 2-71 years old
      (mean 34 years old), 42 males and 12 females. Common racial/ethnic groups were
      non-Hispanic Whites and American Indians (together comprising 72% of all cases).
      Physical findings were often related to the heat carried by the electrical
      current including clothing alterations (29.6%) and burning of skin (53.7%). Most
      deaths occurred on weekend afternoons in summer months, associated with
      recreational activities or agricultural work, and rural locations (77.8%).
      Utilizing the demographic information, clustered events, and associated outdoor
      activities will assist in creating public awareness and provide a framework to
      support targeted warnings in an attempt to prevent future deaths.

PMID- 25053422
TI  - Intra-arterial methylprednisolone for severe steroid refractory gastrointestinal
      graft-versus-host disease.
AB  - Acute graft versus host disease (GVHD) is a significant complication of bone
      marrow transplantation with approximately half of patients being refractory to
      steroids. There are numerous second-line systemic immunosuppressive treatments
      but the overall prognosis is poor and these therapies are associated with high
      mortality due to infection. An alternative approach to systemic treatment for
      GVHD is targeted delivery of immunosuppression. We present two pediatric cases
      with steroid-refractory gastrointestinal GVHD who clinically responded to intra
      arterial steroid administration. We also review the literature regarding this
      treatment modality with a particular emphasis in children.

PMID- 25053423
TI  - Modeling Coastal Salinity in Quasi 2D and 3D Using a DUALEM-421 and Inversion
      Software.
AB  - Rising sea levels, owing to climate change, are a threat to fresh water coastal
      aquifers. This is because saline intrusions are caused by increases and
      intensification of medium-large scale influences including sea level rise, wave
      climate, tidal cycles, and shifts in beach morphology. Methods are therefore
      required to understand the dynamics of these interactions. While traditional
      borehole and galvanic contact resistivity (GCR) techniques have been successful
      they are time-consuming. Alternatively, frequency-domain electromagnetic (FEM)
      induction is potentially useful as physical contact with the ground is not
      required. A DUALEM-421 and EM4Soil inversion software package are used to develop
      a quasi two- (2D) and quasi three-dimensional (3D) electromagnetic conductivity
      images (EMCI) across Long Reef Beach located north of Sydney Harbour, New South
      Wales, Australia. The quasi 2D models discern: the dry sand (<10 mS/m) associated
      with the incipient dune; sand with fresh water (10 to 20 mS/m); mixing of fresh
      and saline water (20 to 500 mS/m), and; saline sand of varying moisture (more
      than 500 mS/m). The quasi 3D EMCIs generated for low and high tides suggest that
      daily tidal cycles do not have a significant effect on local groundwater
      salinity. Instead, the saline intrusion is most likely influenced by medium-large
      scale drivers including local wave climate and morphology along this wave
      dominated beach. Further research is required to elucidate the influence of
      spring-neap tidal cycles, contrasting beach morphological states and sea level
      rise. 

PMID- 25053424
TI  - Purification and biochemical properties of multiple xylanases from Aspergillus
      ochraceus tolerant to Hg2+ ion and a wide range of pH.
AB  - Production of multiple xylanases, in which each enzyme has a specific
      characteristic, can be one strategy to achieve the effective hydrolysis of xylan.
      Three xylanases (xyl 1, xyl 2, and xyl 3) from Aspergillus ochraceus were
      purified by chromatography using diethylaminoethyl (DEAE) cellulose, Biogel P-60,
      and Sephadex G-100 columns. These enzymes are glycoproteins of low molecular
      weight with an optimum temperature at 60  degrees C. The glycosylation presented
      is apparently not related to thermostability, since xyl 3 (20 % carbohydrate) was
      more thermostable than xyl 2 (67 % carbohydrate). Xyl 3 was able to retain most
      of its activity in a wide range of pH (3.5-8.0), while xyl 1 and xyl 2 presented
      optimum pH of 6.0. Xyl 1 and xyl 2 were activated by 5 and 10 mM MnCl2 and CoCl2,
      while xyl 3 was activated by 1 mM of the same compounds. Interestingly, xyl 2
      presented high tolerance toward mercury ion. Xylanases from A. ochraceus
      hydrolyzed xylans of different origins, such as birchwood, oat spelt, larchwood,
      and eucalyptus (around 90 % or more), except xyl 2 and xyl 3 that hydrolyzed with
      lesser efficiency eucalyptus (66.7 %) and oat spelt (44.8 %) xylans.

PMID- 25053425
TI  - The POU-er of gene nomenclature.
AB  - The pluripotency factor POU5F1 (OCT4) is well known as a key regulator of stem
      cell fate. Homologues of POU5F1 exist throughout vertebrates, but the
      evolutionary and functional relationships between the various family members have
      been unclear. The level to which function has been conserved within this family
      provides insight into the evolution of early embryonic potency. Here, we seek to
      clarify the relationship between POU5F1 homologues in the vertebrate lineage,
      both phylogenetically and functionally. We resolve the confusion over the
      identity of the zebrafish gene, which was originally named pou2, then changed to
      pou5f1 and again, more recently, to pou5f3. We argue that the use of correct
      nomenclature is crucial when discussing the degree to which the networks
      regulating early embryonic differentiation are conserved. 

PMID- 25053426
TI  - The dynamics of plant plasma membrane proteins: PINs and beyond.
AB  - Plants are permanently situated in a fixed location and thus are well adapted to
      sense and respond to environmental stimuli and developmental cues. At the
      cellular level, several of these responses require delicate adjustments that
      affect the activity and steady-state levels of plasma membrane proteins. These
      adjustments involve both vesicular transport to the plasma membrane and protein
      internalization via endocytic sorting. A substantial part of our current
      knowledge of plant plasma membrane protein sorting is based on studies of PIN
      FORMED (PIN) auxin transport proteins, which are found at distinct plasma
      membrane domains and have been implicated in directional efflux of the plant
      hormone auxin. Here, we discuss the mechanisms involved in establishing such
      polar protein distributions, focusing on PINs and other key plant plasma membrane
      proteins, and we highlight the pathways that allow for dynamic adjustments in
      protein distribution and turnover, which together constitute a versatile
      framework that underlies the remarkable capabilities of plants to adjust growth
      and development in their ever-changing environment. 

PMID- 25053427
TI  - Insm1 promotes endocrine cell differentiation by modulating the expression of a
      network of genes that includes Neurog3 and Ripply3.
AB  - Insulinoma associated 1 (Insm1) plays an important role in regulating the
      development of cells in the central and peripheral nervous systems, olfactory
      epithelium and endocrine pancreas. To better define the role of Insm1 in
      pancreatic endocrine cell development we generated mice with an Insm1(GFPCre)
      reporter allele and used them to study Insm1-expressing and null populations.
      Endocrine progenitor cells lacking Insm1 were less differentiated and exhibited
      broad defects in hormone production, cell proliferation and cell migration.
      Embryos lacking Insm1 contained greater amounts of a non-coding Neurog3 mRNA
      splice variant and had fewer Neurog3/Insm1 co-expressing progenitor cells,
      suggesting that Insm1 positively regulates Neurog3. Moreover, endocrine
      progenitor cells that express either high or low levels of Pdx1, and thus may be
      biased towards the formation of specific cell lineages, exhibited cell type
      specific differences in the genes regulated by Insm1. Analysis of the function of
      Ripply3, an Insm1-regulated gene enriched in the Pdx1-high cell population,
      revealed that it negatively regulates the proliferation of early endocrine cells.
      Taken together, these findings indicate that in developing pancreatic endocrine
      cells Insm1 promotes the transition from a ductal progenitor to a committed
      endocrine cell by repressing a progenitor cell program and activating genes
      essential for RNA splicing, cell migration, controlled cellular proliferation,
      vasculogenesis, extracellular matrix and hormone secretion. 

PMID- 25053428
TI  - Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation
      during thymus organogenesis.
AB  - The thymus and parathyroid glands arise from a shared endodermal primordium in
      the third pharyngeal pouch (3rd pp). Thymus fate is specified in the ventral 3rd
      pp between E9.5 and E11, whereas parathyroid fate is specified in the dorsal
      domain. The molecular mechanisms that specify fate and regulate thymus and
      parathyroid development are not fully delineated. Previous reports suggested that
      Tbx1 is required for thymus organogenesis because loss of Tbx1 in individuals
      with DiGeorge syndrome and in experimental Tbx1 deletion mutants is associated
      with thymus aplasia or hypoplasia. However, the thymus phenotype is likely to be
      secondary to defects in pharyngeal pouch formation. Furthermore, the absence of
      Tbx1 expression in the thymus-fated domain of the wild-type 3rd pp suggested that
      Tbx1 is instead a negative regulator of thymus organogenesis. To test this
      hypothesis, we generated a novel mouse strain in which expression of a
      conditional Tbx1 allele was ectopically activated in the thymus-fated domain of
      the 3rd pp. Ectopic Tbx1 expression severely repressed expression of Foxn1, a
      transcription factor that marks the thymus-fated domain and is required for
      differentiation and proliferation of thymic epithelial cell (TEC) progenitors. By
      contrast, ectopic Tbx1 did not alter the expression pattern of Gcm2, a
      transcription factor restricted to the parathyroid-fated domain and required for
      parathyroid development. Ectopic Tbx1 expression impaired TEC proliferation and
      arrested TEC differentiation at an early progenitor stage. The results support
      the hypothesis that Tbx1 negatively regulates TEC growth and differentiation, and
      that extinction of Tbx1 expression in 3rd pp endoderm is a prerequisite for
      thymus organogenesis. 

PMID- 25053429
TI  - Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R
      spondin3.
AB  - A complex regulatory network of morphogens and transcription factors is essential
      for normal cardiac development. Nkx2-5 is among the earliest known markers of
      cardiac mesoderm that is central to the regulatory pathways mediating second
      heart field (SHF) development. Here, we have examined the specific requirements
      for Nkx2-5 in the SHF progenitors. We show that Nkx2-5 potentiates Wnt signaling
      by regulating the expression of the R-spondin3 (Rspo3) gene during cardiogenesis.
      R-spondins are secreted factors and potent Wnt agonists that in part regulate
      stem cell proliferation. Our data show that Rspo3 is markedly downregulated in
      Nkx2-5 mutants and that Rspo3 expression is regulated by Nkx2-5. Conditional
      inactivation of Rspo3 in the Isl1 lineage resulted in embryonic lethality
      secondary to impaired development of SHF. More importantly, we find that Wnt
      signaling is significantly attenuated in Nkx2-5 mutants and that enhancing
      Wnt/beta-catenin signaling by pharmacological treatment or by transgenic
      expression of Rspo3 rescues the SHF defects in the conditional Nkx2-5(+/-)
      mutants. We have identified a previously unrecognized genetic link between Nkx2-5
      and Wnt signaling that supports continued cardiac growth and proliferation during
      development. Identification of Rspo3 in cardiac development provides a new
      paradigm in temporal regulation of Wnt signaling by cardiac-specific
      transcription factors. 

PMID- 25053430
TI  - Retinoic acid controls body axis extension by directly repressing Fgf8
      transcription.
AB  - Retinoic acid (RA) generated in the mesoderm of vertebrate embryos controls body
      axis extension by downregulating Fgf8 expression in cells exiting the caudal
      progenitor zone. RA activates transcription by binding to nuclear RA receptors
      (RARs) at RA response elements (RAREs), but it is unknown whether RA can directly
      repress transcription. Here, we analyzed a conserved RARE upstream of Fgf8 that
      binds RAR isoforms in mouse embryos. Transgenic embryos carrying Fgf8 fused to
      lacZ exhibited expression similar to caudal Fgf8, but deletion of the RARE
      resulted in ectopic trunk expression extending into somites and neuroectoderm.
      Epigenetic analysis using chromatin immunoprecipitation of trunk tissues from
      E8.25 wild-type and Raldh2(-/-) embryos lacking RA synthesis revealed RA
      dependent recruitment of the repressive histone marker H3K27me3 and polycomb
      repressive complex 2 (PRC2) near the Fgf8 RARE. The co-regulator RERE, the loss
      of which results in ectopic Fgf8 expression and somite defects, was recruited
      near the RARb RARE by RA, but was released from the Fgf8 RARE by RA. Our findings
      demonstrate that RA directly represses Fgf8 through a RARE-mediated mechanism
      that promotes repressive chromatin, thus providing valuable insight into the
      mechanism of RA-FGF antagonism during progenitor cell differentiation. 

PMID- 25053431
TI  - The F-box protein Slmb restricts the activity of aPKC to polarize epithelial
      cells.
AB  - The Par-3/Par-6/aPKC complex is the primary determinant of apical polarity in
      epithelia across animal species, but how the activity of this complex is
      restricted to allow polarization of the basolateral domain is less well
      understood. In Drosophila, several multiprotein modules antagonize the Par
      complex through a variety of means. Here we identify a new mechanism involving
      regulated protein degradation. Strong mutations in supernumerary limbs (slmb),
      which encodes the substrate adaptor of an SCF-class E3 ubiquitin ligase, cause
      dramatic loss of polarity in imaginal discs accompanied by tumorous proliferation
      defects. Slmb function is required to restrain apical aPKC activity in a manner
      that is independent of endolysosomal trafficking and parallel to the Scribble
      module of junctional scaffolding proteins. The involvement of the Slmb E3 ligase
      in epithelial polarity, specifically limiting Par complex activity to distinguish
      the basolateral domain, points to parallels with polarization of the C. elegans
      zygote. 

PMID- 25053432
TI  - Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial
      polarity.
AB  - The Drosophila anterior-posterior axis is specified when the posterior follicle
      cells signal to polarise the oocyte, leading to the anterior/lateral localisation
      of the Par-6/aPKC complex and the posterior recruitment of Par-1, which induces a
      microtubule reorganisation that localises bicoid and oskar mRNAs. Here we show
      that oocyte polarity requires Slmb, the substrate specificity subunit of the SCF
      E3 ubiquitin ligase that targets proteins for degradation. The Par-6/aPKC complex
      is ectopically localised to the posterior of slmb mutant oocytes, and Par-1 and
      oskar mRNA are mislocalised. Slmb appears to play a related role in epithelial
      follicle cells, as large slmb mutant clones disrupt epithelial organisation,
      whereas small clones show an expansion of the apical domain, with increased
      accumulation of apical polarity factors at the apical cortex. The levels of aPKC
      and Par-6 are significantly increased in slmb mutants, whereas Baz is slightly
      reduced. Thus, Slmb may induce the polarisation of the anterior-posterior axis of
      the oocyte by targeting the Par-6/aPKC complex for degradation at the oocyte
      posterior. Consistent with this, overexpression of the aPKC antagonist Lgl
      strongly rescues the polarity defects of slmb mutant germline clones. The role of
      Slmb in oocyte polarity raises an intriguing parallel with C. elegans axis
      formation, in which PAR-2 excludes the anterior PAR complex from the posterior
      cortex to induce polarity, but its function can be substituted by overexpressing
      Lgl. 

PMID- 25053433
TI  - The cellular and molecular etiology of the craniofacial defects in the avian
      ciliopathic mutant talpid2.
AB  - talpid(2) is an avian autosomal recessive mutant with a myriad of congenital
      malformations, including polydactyly and facial clefting. Although phenotypically
      similar to talpid(3), talpid(2) has a distinct facial phenotype and an unknown
      cellular, molecular and genetic basis. We set out to determine the etiology of
      the craniofacial phenotype of this mutant. We confirmed that primary cilia were
      disrupted in talpid(2) mutants. Molecularly, we found disruptions in Hedgehog
      signaling. Post-translational processing of GLI2 and GLI3 was aberrant in the
      developing facial prominences. Although both GLI2 and GLI3 processing were
      disrupted in talpid(2) mutants, only GLI3 activator levels were significantly
      altered in the nucleus. Through additional fine mapping and whole-genome
      sequencing, we determined that the talpid(2) phenotype was linked to a 1.4 Mb
      region on GGA1q that contained the gene encoding the ciliary protein C2CD3. We
      cloned the avian ortholog of C2CD3 and found its expression was ubiquitous, but
      most robust in the developing limbs and facial prominences. Furthermore, we found
      that C2CD3 is localized proximal to the ciliary axoneme and is important for
      docking the mother centriole to the ciliary vesicle and cell membrane. Finally,
      we identified a 19 bp deletion in talpid(2) C2CD3 that produces a premature stop
      codon, and thus a truncated protein, as the likely causal allele for the
      phenotype. Together, these data provide insight into the cellular, molecular and
      genetic etiology of the talpid(2) phenotype. Our data suggest that, although the
      talpid(2) and talpid(3) mutations affect a common ciliogenesis pathway, they are
      caused by mutations in different ciliary proteins that result in differences in
      craniofacial phenotype. 

PMID- 25053434
TI  - The origin and loss of periodic patterning in the turtle shell.
AB  - The origin of the turtle shell over 200 million years ago greatly modified the
      amniote body plan, and the morphological plasticity of the shell has promoted the
      adaptive radiation of turtles. The shell, comprising a dorsal carapace and a
      ventral plastron, is a layered structure formed by basal endochondral axial
      skeletal elements (ribs, vertebrae) and plates of bone, which are overlain by
      keratinous ectodermal scutes. Studies of turtle development have mostly focused
      on the bones of the shell; however, the genetic regulation of the epidermal
      scutes has not been investigated. Here, we show that scutes develop from an array
      of patterned placodes and that these placodes are absent from a soft-shelled
      turtle in which scutes were lost secondarily. Experimentally inhibiting Shh, Bmp
      or Fgf signaling results in the disruption of the placodal pattern. Finally, a
      computational model is used to show how two coupled reaction-diffusion systems
      reproduce both natural and abnormal variation in turtle scutes. Taken together,
      these placodal signaling centers are likely to represent developmental modules
      that are responsible for the evolution of scutes in turtles, and the regulation
      of these centers has allowed for the diversification of the turtle shell. 

PMID- 25053436
TI  - Loss of focal adhesions in glia disrupts both glial and photoreceptor axon
      migration in the Drosophila visual system.
AB  - Many aspects of glial development are regulated by extracellular signals,
      including those from the extracellular matrix (ECM). Signals from the ECM are
      received by cell surface receptors, including the integrin family. Previously, we
      have shown that Drosophila integrins form adhesion complexes with Integrin-linked
      kinase and talin in the peripheral nerve glia and have conserved roles in glial
      sheath formation. However, integrin function in other aspects of glial
      development is unclear. The Drosophila eye imaginal disc (ED) and optic stalk
      (OS) complex is an excellent model with which to study glial migration,
      differentiation and glia-neuron interactions. We studied the roles of the
      integrin complexes in these glial developmental processes during OS/eye
      development. The common beta subunit betaPS and two alpha subunits, alphaPS2 and
      alphaPS3, are located in puncta at both glia-glia and glia-ECM interfaces.
      Depletion of betaPS integrin and talin by RNAi impaired the migration and
      distribution of glia within the OS resulting in morphological defects. Reduction
      of integrin or talin in the glia also disrupted photoreceptor axon outgrowth
      leading to axon stalling in the OS and ED. The neuronal defects were correlated
      with a disruption of the carpet glia tube paired with invasion of glia into the
      core of the OS and the formation of a glial cap. Our results suggest that
      integrin-mediated extracellular signals are important for multiple aspects of
      glial development and non-autonomously affect axonal migration during Drosophila
      eye development. 

PMID- 25053435
TI  - Hand1 phosphoregulation within the distal arch neural crest is essential for
      craniofacial morphogenesis.
AB  - In this study we examine the consequences of altering Hand1 phosphoregulation in
      the developing neural crest cells (NCCs) of mice. Whereas Hand1 deletion in NCCs
      reveals a nonessential role for Hand1 in craniofacial development and embryonic
      survival, altering Hand1 phosphoregulation, and consequently Hand1 dimerization
      affinities, in NCCs results in severe mid-facial clefting and neonatal death.
      Hand1 phosphorylation mutants exhibit a non-cell-autonomous increase in
      pharyngeal arch cell death accompanied by alterations in Fgf8 and Shh pathway
      expression. Together, our data indicate that the extreme distal pharyngeal arch
      expression domain of Hand1 defines a novel bHLH-dependent activity, and that
      disruption of established Hand1 dimer phosphoregulation within this domain
      disrupts normal craniofacial patterning. 

PMID- 25053437
TI  - Single cell dissection of early kidney development: multilineage priming.
AB  - We used a single cell RNA-seq strategy to create an atlas of gene expression
      patterns in the developing kidney. At several stages of kidney development,
      histologically uniform populations of cells give rise to multiple distinct
      lineages. We performed single cell RNA-seq analysis of total mouse kidneys at
      E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of
      progenitor cell induction driven primarily by gene repression. Surprising
      stochastic expression of marker genes associated with differentiated cell types
      was observed in E11.5 progenitors. We provide a global view of the polarized gene
      expression already present in the renal vesicle, the first epithelial precursor
      of the nephron. We show that Hox gene read-through transcripts can be spliced to
      produce intergenic homeobox swaps. We also identify a surprising number of genes
      with partially degraded noncoding RNA. Perhaps most interesting, at early
      developmental times single cells often expressed genes related to several
      developmental pathways. This provides powerful evidence that initial
      organogenesis involves a process of multilineage priming. This is followed by a
      combination of gene repression, which turns off the genes associated with most
      possible lineages, and the activation of increasing numbers of genes driving the
      chosen developmental direction. 

PMID- 25053439
TI  - Low computed tomography coronary artery calcium scores in familial longevity: the
      Leiden Longevity Study.
AB  - Offspring of long-lived parents have a low prevalence of cardiovascular disease
      in middle age. The purposes of this study were to investigate calcium scores in
      offspring as compared to controls and to determine the influence of
      cardiovascular risk factors. CT coronary artery calcium score was measured in
      offspring of long-lived families (n = 244, 125 males) and their partners (n =
      223, 96 males) who served as controls. Calcium scores were analyzed separately
      for sexes. Subjects were grouped by very low calcium score <=10 and scores above
      10. Nonparametric Mann-Whitney test, chi-squared tests, and logistic regression
      analyses were performed to determine the association between calcium scores,
      familial longevity, and cardiovascular risk factors. More offspring of long-lived
      parents had lower calcium scores than controls. In men, 34 % of offspring had
      score <=10 versus 21 % of controls (odds ratio (OR) and 95 % confidence interval
      (CI) 2.0, 1.08-3.7, p = 0.028). In women, 70 % of offspring had score <=10 versus
      54 % of controls (OR 1.9, 95 % CI 1.13-3.4, p = 0.019). Differences remained
      significant after correction for age (men, p = 0.043 and women, p = 0.003) and
      further correction for major risk factors in women, indicating genetic influence
      for lower calcium scores. In men, the association was found to be influenced by
      cardiovascular risk factors. Men and women with a familial propensity to become
      long-lived have lower coronary artery calcium scores than controls. Low scores
      may indicate a younger biologic arterial age associated with a low risk for
      incident cardiovascular disease.

PMID- 25053440
TI  - Phytotoxicity of trace metals in spiked and field-contaminated soils: Linking
      soil-extractable metals with toxicity.
AB  - Soil tests have been widely developed to predict trace metal uptake by plants.
      The prediction of metal toxicity, however, has rarely been tested. The present
      study was set up to compare 8 established soil tests for diagnosing phytotoxicity
      in contaminated soils. Nine soils contaminated with Zn or Cu by metal mining,
      smelting, or processing were collected. Uncontaminated reference soils with
      similar soil properties were sampled, and series of increasing contamination were
      created by mixing each with the corresponding soil. In addition, each reference
      soil was spiked with either ZnCl2 or CuCl2 at several concentrations. Total metal
      toxicity to barley seedling growth in the field-contaminated soils was up to 30
      times lower than that in corresponding spiked soils. Total metal (aqua regia
      soluble) toxicity thresholds of 50% effective concentrations (EC50) varied by
      factors up to 260 (Zn) or 6 (Cu) among soils. For Zn, variations in EC50
      thresholds decreased as aqua regia > 0.43 M HNO3  > 0.05 M ethylenediamine
      tetraacetic acid (EDTA) > 1 M NH4 NO3  > cobaltihexamine > diffusive gradients in
      thin films (DGT) > 0.001 M CaCl2 , suggesting that the last extraction is the
      most robust phytotoxicity index for Zn. The EDTA extraction was the most robust
      for Cu-contaminated soils. The isotopically exchangeable fraction of the total
      soil metal in the field-contaminated soils markedly explained the lower toxicity
      compared with spiked soils. The isotope exchange method can be used to translate
      soil metal limits derived from soils spiked with metal salts to site-specific
      soil metal limits.

PMID- 25053441
TI  - Axillary reverse mapping in breast cancer: a Canadian experience.
AB  - BACKGROUND: The aim of this study was to evaluate the axillary reverse lymphatic
      mapping (ARM) procedure for reducing the risk of arm lymphedema after breast
      cancer surgery. METHODS: The ARM procedure was carried out with a subareolar
      injection of technetium-99 sulfur colloid the morning of surgery, and a patent
      blue dye injection into the upper inner arm after anesthesia. RESULTS: Fifty-two
      women made up our study population. Thirty-seven patients underwent sentinel
      lymph node biopsy (SLNB) and 15 patients underwent an axillary lymph node
      dissection (ALND) for known nodal metastasis. The sentinel lymph node was
      identified in 36 of the 37 cases who underwent SLNB alone and in 12 of 15
      patients who underwent on ALND. In 13 patients, both blue and radioactive lymph
      nodes or lymphatics were clearly identified (25%) and 5 patients had a clear
      crossover with nodes being both blue and hot. Only a single patient with
      crossover lymphatics had metastases present in their sentinel node. CONCLUSION:
      The ARM technique did not prevent identification of the SLN and we identified
      much greater crossover than reported. We had a single patient, who underwent a
      sentinel node biopsy, with mild arm lymphedema (1.9%) after 2 years of follow up.

PMID- 25053443
TI  - Simultaneous targeting of prostate stem cell antigen and prostate-specific
      membrane antigen improves the killing of prostate cancer cells using a novel
      modular T cell-retargeting system.
AB  - BACKGROUND: Recently, we described a novel modular platform technology in which T
      cell-recruitment and tumor-targeting domains of conventional bispecific
      antibodies are split to independent components, a universal effector module (EM)
      and replaceable monospecific/monovalent target modules (TMs) that form highly
      efficient T cell-retargeting complexes. Theoretically, our unique strategy should
      allow us to simultaneously retarget T cells to different tumor antigens by
      combining the EM with two or more different monovalent/monospecific TMs or even
      with bivalent/bispecific TMs, thereby overcoming limitations of a monospecific
      treatment such as the selection of target-negative tumor escape variants.
      METHODS: In order to advance our recently introduced prostate stem cell antigen
      (PSCA)-specific modular system for a dual-targeting of prostate cancer cells, two
      additional TMs were constructed: a monovalent/monospecific TM directed against
      the prostate-specific membrane antigen (PSMA) and a bivalent/bispecific TM (bsTM)
      with specificity for PSMA and PSCA. The functionality of the novel dual-targeting
      strategies was analyzed by performing T cell activation and chromium release
      assays. RESULTS: Similar to the PSCA-specific modular system, the novel PSMA
      specific modular system mediates an efficient target-dependent and -specific
      tumor cell lysis at low E:T ratios and picomolar Ab concentrations. Moreover, by
      combination of the EM with either the bispecific TM directed to PSMA and PSCA or
      both monospecifc TMs directed to either PSCA or PSMA, dual-specific targeting
      complexes were formed which allowed us to kill potential escape variants
      expressing only one or the other target antigen. CONCLUSIONS: Overall, the novel
      modular system represents a promising tool for multiple tumor targeting.

PMID- 25053442
TI  - Nanogel--an advanced drug delivery tool: Current and future.
AB  - Nanogels are robust nanoparticles that could be used to deliver active drug
      compounds in controlled drug delivery applications. Nanogels drug delivery system
      is more effective and safer for both hydrophilic and hydrophobic drugs due to
      their chemical composition and formulations that are inappropriate for other
      formulations. Nanogels have enabled enlargement of functionalized nanoparticles,
      which act as a drug carriers that can be loaded with drugs and other active
      material to be released in a controlled manner at specific site. This review aims
      at providing general introduction on nanogels, recent synthesis methodology and
      their novel application in different fields. 

PMID- 25053444
TI  - Does rare use of assistive devices during patient handling increase the risk of
      low back pain? A prospective cohort study among female healthcare workers.
AB  - PURPOSE: To investigate whether rare use of assistive devices during patient
      handling increases the respective risk for infrequent and frequent low back pain
      (LBP) among female healthcare workers reporting to be free of LBP at baseline.
      METHOD: Female healthcare workers replied to questionnaires about use of
      assistive devices during patient handling activities (rarely, occasionally and
      often) and LBP in both 2005 and 2006. Among those reporting to be free of LBP (0
      days the past 12 months) in 2005 (n = 1,478), the multi-adjusted odds ratio for
      developing infrequent LBP (1-30 days the past 12 months) and frequent LBP (>30
      days the past 12 months) in 2006 depending on use of assistive devices was
      prospectively investigated. RESULTS: The multi-adjusted odds ratio for developing
      infrequent LBP was 1.21 (95 % CI 0.90-1.62) for those occasionally using
      assistive devices, and 1.78 (95 % CI 1.19-2.66) for those rarely using assistive
      devices, referencing healthcare workers often using assistive devices during
      patient handling (p < 0.01 for trend). No associations between use of assistive
      devices during patient handling and risk of frequent LBP were found. CONCLUSION:
      The study indicates that rare use of assistive devices can increase the risk for
      developing infrequent LBP in female healthcare workers reporting to be free from
      LBP at baseline.

PMID- 25053445
TI  - Ordered monolayers of free-standing porphyrins on gold.
AB  - The controlled attachment of chromophores to metal or semiconducting surfaces is
      a prerequisite for the construction of photonic devices and artificial surface
      based light-harvesting systems. We present an approach to mount porphyrins in
      ordered monolayers on Au(111) by self-assembly and verify it, employing STM,
      absorption spectroscopy, and quantum chemical calculations. The usual adsorption
      geometry of planar chromophores, flat on the surface or densely packed edge-on,
      is prevented by mounting the porphyrins upright on a molecular platform. An
      ethynyl unit as spacer and pivot joint provides almost free azimuthal rotation of
      the unsubstituted porphin. However, rotation of the larger triphenylporphyrin
      unit is sterically restricted: because the diameter of the substituted porphyrin
      is larger than the distance to its next neighbors, the phenyl substituents of
      neigboring molecules interact by dispersion force, which leads to an alignment of
      the azimuthal rotators. 

PMID- 25053446
TI  - Brain and behaviour of living and extinct echidnas.
AB  - The Tachyglossidae (long- and short-beaked echidnas) are a family of monotremes,
      confined to Australia and New Guinea, that exhibit striking trigeminal, olfactory
      and cortical specialisations. Several species of long-beaked echidna (Zaglossus
      robusta, Zaglossus hacketti, Megalibgwilia ramsayi) were part of the large-bodied
      (10 kg or more) fauna of Pleistocene Australasia, but only the diminutive (2-7
      kg) Tachyglossus aculeatus is widespread today on the Australian mainland. We
      used high-resolution CT scanning and other osteological techniques to determine
      whether the remarkable neurological specialisations of modern echidnas were also
      present in Pleistocene forms or have undergone modification as the Australian
      climate changed in the transition from the Pleistocene to the Holocene. All the
      living and extinct echidnas studied have a similar pattern of cortical
      gyrification that suggests comparable functional topography to the modern short
      beaked form. Osteological features related to olfactory, trigeminal, auditory and
      vestibular specialisation (e.g., foramina and cribriform plate area, osseous
      labyrinth topography) are also similar in living and extinct species. Our
      findings indicate that despite differences in diet, habitat and body size, the
      suite of neurological specialisations in the Tachyglossidae has been remarkably
      constant: encephalisation, sensory anatomy and specialisation (olfactory,
      trigeminal, auditory and vestibular), hypoglossal nerve size and cortical
      topography have all been stable neurological features of the group for at least
      300,000 years.

PMID- 25053447
TI  - Medical consensus, guidelines, and position papers: a policy for the ECFS.
AB  - The terms consensus, guideline and position paper are sometimes employed as if
      they were interchangeable, but the purpose of such documents and the robustness
      of advice vary as the evidence base does not have the same depth in each. The
      Board of the European Cystic Fibrosis Society deemed it to be helpful to provide
      a short commentary on the definition of these terms, on their interconnections
      and on how ECFS considers them in documents endorsed by the society. 

PMID- 25053448
TI  - Peripheral thermosensation in mammals.
AB  - Our ability to perceive temperature is crucial: it enables us to swiftly react to
      noxiously cold or hot objects and helps us to maintain a constant body
      temperature. Sensory nerve endings, upon depolarization by temperature-gated ion
      channels, convey electrical signals from the periphery to the CNS, eliciting a
      sense of temperature. In the past two decades, we have witnessed important
      advances in our understanding of mammalian thermosensation, with the
      identification and animal-model assessment of candidate molecular thermosensors -
      such as types of transient receptor potential (TRP) cation channels - involved in
      peripheral thermosensation. Ongoing research aims to understand how these
      miniature thermometers operate at the cellular and molecular level, and how they
      can be pharmacologically targeted to treat pain without disturbing vital
      thermoregulatory processes. 

PMID- 25053449
TI  - Liver collagen in cirrhosis correlates with portal hypertension and liver
      dysfunction.
AB  - Liver collagen proportionate area (CPA) assessed by computer-assisted digital
      image analysis has been proposed as an accurate and objective histological
      variable for subclassifying cirrhosis. The study aimed to examine the
      relationship between CPA and relevant clinical parameters in cirrhotic patients
      and to evaluate the sampling variability for CPA. The study included 48
      consecutive liver transplantation patients with established cirrhosis. Hepatic
      venous pressure gradient (HVPG) and serum markers of liver failure were
      determined prior to transplantation. CPA was assessed in the explanted livers. In
      20 of the livers, CPA was measured in more than one tissue sample. CPA showed
      significant correlations with HVPG and with various surrogate markers of hepatic
      dysfunction including albumin, bilirubin, INR, MELD score and Child-Pugh score.
      CPA reliably discriminated HVPG >=10 mmHg, termed 'clinically significant portal
      hypertension' (area under receiver operator curve: 0.923, p < 0.001; odds ratio:
      1.209, p = 0.003). CPA measured on tissue blocks showed no significant sampling
      variability (p > 0.5). In conclusion, the study correlated portal hypertension
      and hepatic dysfunction with the amount of collagen in cirrhotic livers. The
      findings support the presumption of CPA as a useful histological marker for
      subclassifying cirrhosis and as a helpful supplement to the qualitative
      description of hepatic architectural changes in routine pathology.

PMID- 25053451
TI  - Theoretical two-atom thick semiconducting carbon sheet.
AB  - A two-dimensional carbon allotrope, H-net, is proposed using first principle
      calculations. H-net incorporates C4 distorted squares, C6 hexagons, and C8
      octagons. Unlike previously reported planar graphene and other theoretical carbon
      sheets, H-net is a two-atom thick polymorph with identical C6 + C4 + C6
      components cross-facing and covalently buckled to feature a handshake-like model.
      The feasibility of H-net is evident from its dynamic stability as confirmed by
      phonon-mode analysis and its lower total energy. H-net is energetically more
      favorable than synthesized graphdiyne and theoretical graphyne, BPC, S-graphene,
      polycyclic net, alpha-squarographite, and lithographite. We explored a possible
      route for the synthesis of H-net from graphene nanoribbons. Electronic band
      structure calculations indicated that H-net is a semiconductor with an indirect
      band gap of 2.11 eV, whereas graphene and many other two-dimensional carbon
      sheets are metallic. We also explored the electronic structure of one-dimensional
      nanoribbons derived from H-net. The narrowest H-net nanoribbon showed metallic
      behavior, whereas the other nanoribbons are semiconductors with band gaps that
      increase as the nanoribbons widen. H-net and its tailored nanoribbons are
      expected to possess more electronic properties than graphene because of their
      exceptional crystal structure and different energy band gaps. 

PMID- 25053450
TI  - Genome-enabled predictions for binomial traits in sugar beet populations.
AB  - BACKGROUND: Genomic information can be used to predict not only continuous but
      also categorical (e.g. binomial) traits. Several traits of interest in human
      medicine and agriculture present a discrete distribution of phenotypes (e.g.
      disease status). Root vigor in sugar beet (B. vulgaris) is an example of binomial
      trait of agronomic importance. In this paper, a panel of 192 SNPs (single
      nucleotide polymorphisms) was used to genotype 124 sugar beet individual plants
      from 18 lines, and to classify them as showing "high" or "low" root vigor.
      RESULTS: A threshold model was used to fit the relationship between binomial root
      vigor and SNP genotypes, through the matrix of genomic relationships between
      individuals in a genomic BLUP (G-BLUP) approach. From a 5-fold cross-validation
      scheme, 500 testing subsets were generated. The estimated average cross
      validation error rate was 0.000731 (0.073%). Only 9 out of 12326 test
      observations (500 replicates for an average test set size of 24.65) were
      misclassified. CONCLUSIONS: The estimated prediction accuracy was quite high.
      Such accurate predictions may be related to the high estimated heritability for
      root vigor (0.783) and to the few genes with large effect underlying the trait.
      Despite the sparse SNP panel, there was sufficient within-scaffold LD where SNPs
      with large effect on root vigor were located to allow for genome-enabled
      predictions to work.

PMID- 25053452
TI  - UNGASS 2016 on drugs, the first challenge for HIV advocates in the post-2015 era.

PMID- 25053453
TI  - Modeling the economic impact of linezolid versus vancomycin in confirmed
      nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.
AB  - INTRODUCTION: We compared the economic impacts of linezolid and vancomycin for
      the treatment of hospitalized patients with methicillin-resistant Staphylococcus
      aureus (MRSA)-confirmed nosocomial pneumonia. METHODS: We used a 4-week decision
      tree model incorporating published data and expert opinion on clinical
      parameters, resource use and costs (in 2012 US dollars), such as efficacy,
      mortality, serious adverse events, treatment duration and length of hospital
      stay. The results presented are from a US payer perspective. The base case first
      line treatment duration for patients with MRSA-confirmed nosocomial pneumonia was
      10 days. Clinical treatment success (used for the cost-effectiveness ratio) and
      failure due to lack of efficacy, serious adverse events or mortality were
      possible clinical outcomes that could impact costs. Cost of treatment and
      incremental cost-effectiveness per successfully treated patient were calculated
      for linezolid versus vancomycin. Univariate (one-way) and probabilistic
      sensitivity analyses were conducted. RESULTS: The model allowed us to calculate
      the total base case inpatient costs as $46,168 (linezolid) and $46,992
      (vancomycin). The incremental cost-effectiveness ratio favored linezolid (versus
      vancomycin), with lower costs ($824 less) and greater efficacy (+2.7% absolute
      difference in the proportion of patients successfully treated for MRSA nosocomial
      pneumonia). Approximately 80% of the total treatment costs were attributed to
      hospital stay (primarily in the intensive care unit). The results of our
      probabilistic sensitivity analysis indicated that linezolid is the cost-effective
      alternative under varying willingness to pay thresholds. CONCLUSION: These model
      results show that linezolid has a favorable incremental cost-effectiveness ratio
      compared to vancomycin for MRSA-confirmed nosocomial pneumonia, largely
      attributable to the higher clinical trial response rate of patients treated with
      linezolid. The higher drug acquisition cost of linezolid was offset by lower
      treatment failure-related costs and fewer days of hospitalization.

PMID- 25053454
TI  - Seed oil of Joannesia princeps improves cutaneous wound closure in experimental
      mice.
AB  - Joannesia princeps (Cotieira) is a well known medicinal plant in Brazil, however,
      the therapeutic effects of oil obtained from its seeds have still not been
      demonstrated. The beneficial effects of J. princeps seed oil on cutaneous wound
      healing on the back of experimental mice were investigated. An excisional lesion
      in male Swiss mice (n=20 per group) was topically treated with mineral oil or J.
      princeps seed oil once a day beginning on the day of lesion until the third day
      after wounding. Animals were killed and lesions collected after 14 days. Murine
      skin fibroblast cultures were treated with J. princeps seed oil and fibroblast
      activity was evaluated. In the in vivo assay, J. princeps seed oil increased
      wound contraction and migratory tongue length, but reduced neutrophil and
      macrophage number when compared with the control group. Blood vessel number,
      collagen deposition, and VEGF levels were increased in treated lesions when
      compared with control lesions. However, J. princeps seed oil reduced
      myofibroblast density and carbonyl protein levels when compared with the control
      group. In the in vitro assay, treatment with J. princeps seed oil increased
      fibroblast migration and proliferation, but reduced myofibroblastic
      differentiation in vitro. In conclusion, J. princeps seed oil accelerates wound
      closure increasing angiogenesis, keratinocyte migration, and fibroblast activity
      while reducing inflammatory response and oxidative damage. 

PMID- 25053455
TI  - B7-H1 and B7-H4 expression in colorectal carcinoma: correlation with tumor
      FOXP3(+) regulatory T-cell infiltration.
AB  - B7-H1 and B7-H4 are newly discovered members of the B7-CD28 family. They can
      inhibit T cell activation and proliferation and regulate T cell immune response
      negatively. Both B7-H1 and B7-H4 are expressed in many tumors and are classified
      as co-inhibitors of cell-mediated immunity. FOXP3(+) regulatory T cells (Tregs)
      play an important role in the maintenance of tumor immunity tolerance. However,
      the implication of B7-H1 and B7-H4 expression and their interaction with Tregs
      infiltration in colorectal cancer are unknown. The present study aimed to
      determine the expression of B7-H1 and B7-H4 as well as Tregs infiltration in
      colorectal cancer and to explore the clinical and pathological implication of
      suppressor immune cells and molecules. Frozen sections and immunohistochemical
      assay were undertaken to assess B7-H1, B7-H4 expression and Tregs infiltration in
      fresh specimens collected from 56 patients with colorectal carcinoma. The results
      showed that expression of B7-H1 and B7-H4 in colorectal carcinoma tissues was
      significantly higher than in adjacent normal mucosa (P<0.001). B7-H1 expression
      was positively correlated to the infiltration depth, lymph node metastasis and
      advanced Duke's stage (P<0.05, P<0.05 and P<0.05, respectively), whereas B7-H4
      expression was positively related to the infiltration depth and lymph node
      metastasis (P<0.01 and P<0.05, respectively). Furthermore, Tregs infiltration was
      more frequent in tumor tissue than in adjacent normal mucosa and was associated
      with poor differentiation and positive lymph node metastasis (P<0.01, and P<0.01,
      respectively). The statistical analysis indicated a significant correlation
      between Tregs infiltration and B7-H1 or B7-H4 expression respectively. These
      results suggest that over-expression of B7-H1 and B7-H4 has stronger prognostic
      significance and promote tumor tolerance, and they might contribute to Tregs
      development in the colorectal carcinoma tolerogenic milieu. 

PMID- 25053456
TI  - Ethnic inequalities and sex differences in body mass index among tibet minorities
      in China: implication for overweight and obesity risks.
AB  - OBJECTIVES: In the present study, we for the first time investigated overweight
      and obesity level among Tibet minorities (Deng, Lhoba, Monba) living in remote
      villages at the south slope of Qinghai-Tibetan Plateau, China. For each
      ethnicity, the total number of population is less than 10 thousands in China.
      METHODS: Anthropometric measurements were conducted on adult participants of
      three ethnicities in Tibet, China. Totally, the whole sample consists of 141
      males and 163 females. Body mass index (BMI) was adopted to evaluate the
      overweight and obesity level. RESULTS: Within each ethnicity, there was no
      significant sex difference on BMI. The general prevalence of overweight and
      obesity level of Lhoba ethnicity (18.42%) is higher than that of Monba (17.65%)
      and Deng ethnicity (6.29%). For each sex, the distribution of BMI classification
      was found to be significantly associated with ethnicity identity. CONCLUSION: One
      possible reason for ethnic disparity among Tibet minorities in the present study
      is special dietary elements. Measures to prevent and cope with the problem of
      overweight and obesity among Tibet minorities are urgently required.

PMID- 25053457
TI  - Is it an eating disorder or achalasia or both? A literature review and diagnostic
      challenges.
AB  - INTRODUCTION: Achalasia is a rare oesophageal motility disorder characterized by
      physical, behavioural and psychosocial features that are strikingly similar to
      eating disorders (ED). METHOD: A literature search of PubMed and Google Scholar
      identified 36 cases of achalasia from 11 countries misdiagnosed as ED between
      1980 and 2013. RESULTS: On average, the typical misdiagnosed case was an 18-year
      old female with an average weight loss of 16.2 kg. Vomiting behaviour in
      achalasia was distinguished by occurring after both solids and liquids, occurring
      in public, and worsening at night or while lying down, and was associated with
      pain relief. Manometric investigations of oesophageal functioning in clinical ED
      samples are few and have shown little evidence of dysmotility. DISCUSSION:
      Achalasia and ED share numerous clinical features including weight loss and
      vomiting. Pain associated with swallowing difficulties may lead to an
      increasingly restricted pattern of eating and food avoidance. Increased awareness
      of achalasia in ED treatment settings can help facilitate detection of achalasia,
      thereby reducing treatment delay.

PMID- 25053458
TI  - Psychological wellness and health-related stigma: a pilot study of an acceptance
      focused cognitive behavioural intervention for people with lung cancer.
AB  - People with lung cancer experience health-related stigma that is related to
      poorer psychosocial and quality of life outcomes. The present Phase 1 study
      applied mixed methods to test the acceptability of an acceptance-focused
      cognitive behavioural intervention targeting stigma for this patient group.
      Fourteen lung cancer patients completed a 6-week Psychological Wellness
      intervention with pre- and post-test outcome measures of psychological and cancer
      specific distress, depression, health-related stigma and quality of life. In
      depth interviews applying interpretative phenomenological analysis assessed
      participants' experiences of the intervention. Moderate to large improvements
      were observed in psychological (etap (2)  = 0.182) and cancer-specific distress
      (etap (2)  = 0.056); depression (etap (2)  = 0.621); health-related stigma (etap
      (2)  = 0.139). In contrast, quality of life declined (etap (2)  = 0.023). The
      therapeutic relationship; self-management of distress; and relationship support
      were highly valued aspects of the intervention. Barriers to intervention included
      avoidance and practical issues. The lung cancer patients who completed the
      Psychological Wellness intervention reported improvements in psychological
      outcomes and decreases in stigma in the face of declining quality of life with
      patients reporting personal benefit from their own perspectives. A randomised
      controlled trial is warranted to establish the effectiveness of this approach. 

PMID- 25053459
TI  - Peer physical examination policy.

PMID- 25053460
TI  - Cognitive reserve in stroke and traumatic brain injury patients.
AB  - Cognitive reserve (CR) is defined as the ability to cope with brain damage due to
      pre-existing cognitive processes or to the development of new compensatory
      processes. Existing research on CR is mostly based on the study of
      neurodegenerative disorders, such as Alzheimer's disease. Recently, however, this
      construct has also been applied to other neurological conditions, including
      multiple sclerosis, Parkinson's disease, epilepsy, stroke, and traumatic brain
      injury. The present review provides an overview of the studies that have
      investigated the influence of CR on neuropsychological outcome in stroke and
      traumatic brain injury patients. We performed a selective search on MEDLINE,
      CINAHL, and Web of Science Core Collection, using specific keywords including
      "cognitive reserve", "stroke", and "traumatic brain injury". The review is
      organized as follows: the first section focuses on works investigating the effect
      of CR on neuropsychological outcomes in post-stroke patients; the second section
      discusses studies which support the CR theory in traumatic brain injury. This
      review suggests that the study of CR in adult brain injury is still insufficient.
      Future research should investigate the role of other variables, like cognitive
      and social activities, as markers of CR in patients with brain injury, functional
      brain correlates of CR in brain activity, and the effect of CR on brain injury
      rehabilitative outcomes. 

PMID- 25053461
TI  - Angioedema after rt-PA treatment in acute ischemic stroke may be attended by
      shock and worsening of stroke outcome.

PMID- 25053462
TI  - Findings from the native navigators and the Cancer Continuum (NNACC) study.
AB  - Native Navigators and the Cancer Continuum (NNACC) was a community based
      participatory research study among Native American Cancer Research Corporation,
      CO; Inter-Tribal Council of Michigan, MI; Rapid City Regional Hospital's Walking
      Forward, SD; Great Plains Tribal Chairman's' Health Board, SD; and Muscogee
      (Creek) Nation, OK. The project goal was to collaborate, refine, expand, and
      adapt navigator/community education programs to address American Indian
      communities' and patients' needs across the continuum of cancer care (prevention
      through end-of-life). The intervention consisted of four to six site-specific
      education workshop series at all five sites. Each series encompassed 24 h of
      community education. The Social Ecology Theory guided intervention development;
      community members from each site helped refine education materials. Following
      extensive education, Native Patient Navigators (NPNs) implemented the workshops,
      referred participants to cancer screenings, helped participants access local
      programs and resources, and assisted those with cancer to access quality cancer
      care in a timely manner. The intervention was highly successful; 1,964 community
      participants took part. Participants were primarily American Indians (83 %),
      female (70 %) and between 18 and 95 years of age. The education programs
      increased community knowledge by 28 %, facilitated referral to local services,
      and, through site-specific navigation services, improved access to care for 77
      participants diagnosed with cancer during the intervention. Approximately, 90 %
      of participants evaluated workshop content as useful and 92.3 % said they would
      recommend the workshop to others. The intervention successfully increased
      community members' knowledge and raised the visibility of the NPNs in all five
      sites.

PMID- 25053463
TI  - Literature review: The effects of teriparatide therapy at the hip in patients
      with osteoporosis.
AB  - Teriparatide is a skeletal anabolic treatment for patients with osteoporosis at
      high risk for fracture. Because adequate clinical trials have not yet been
      conducted to assess the efficacy of teriparatide for reducing the risk of hip
      fracture, we review here the literature regarding how treatment with teriparatide
      affects the hip in patients with osteoporosis. Teriparatide increases cancellous
      bone volume, improves bone architecture, and - uniquely among osteoporosis
      treatments - increases cortical thickness and cortical porosity. By bone scan and
      positron emission tomography, teriparatide increases bone formation throughout
      the skeleton, including the hip. Consistent with these findings, studies using
      dual-energy X-ray absorptiometry and quantitative computed tomography for
      longitudinal assessment of changes at the hip have consistently shown increases
      in areal and volumetric bone mineral density, cortical thickness, and finite
      element-estimated hip strength in patients treated with teriparatide. Finally, in
      clinical fracture-outcome trials, treatment with teriparatide has been shown to
      reduce the risk of nonvertebral fracture, a composite endpoint that includes hip
      fracture. Taken together, this body of evidence suggests that teriparatide
      positively affects the hip in patients with osteoporosis. 

PMID- 25053464
TI  - A novel mutation for disseminated superficial actinic porokeratosis in the MVK
      gene.

PMID- 25053465
TI  - Depressive symptoms postpartum among parents are associated with marital
      separation: a Swedish cohort study.
AB  - AIMS: To study whether there is an association between dyadic consensus,
      depressive symptoms, and parental stress during early parenthood and marital
      separation 6-8 years after childbirth, among couples in Sweden. METHODS: At
      baseline, 393 couples were included. The couples answered three questionnaires,
      including: Dyadic consensus at 1 week post-partum, depressive symptoms at 3
      months post-partum and parental stress at 18 months post-partum. The parents'
      addresses were followed up after 6-8 years, to study the marital separation rate.
      RESULTS: We found, 6-8 years after childbirth, that 20% of study couples were
      separated. Separation was associated with less dyadic consensus (mothers p <
      0.001; fathers p < 0.001), depressive symptoms (mothers p = 0.022; fathers p =
      0.041) and parental stress (mothers p = 0.002; fathers p = 0.040). The hazard
      ratio (HR) for marital separation was related to dyadic consensus for fathers (HR
      0.51; 95% CI 0.28-0.92), depressive symptoms for mothers (HR 1.69; 95% CI 1.01
      2.84) and fathers (HR 1.92; 95% CI 1.12-3.28), and the mother's parental stress
      (HR 2.16; 95% CI 1.14-4.07). CONCLUSIONS: Understanding how dyadic consensus,
      depressive symptoms and parental stress are associated with marital separation is
      important for health professionals it could be useful in developing interventions
      to provide parents with adequate support during pregnancy and early parenthood
      this knowledge is also important for the public parents should get support in
      pregnancy and while bringing up children, which may help prevent marital
      separation and optimize conditions for the children.

PMID- 25053466
TI  - The association between economic recession and public support for increased
      tobacco taxation in 27 European countries.
AB  - BACKGROUND: Increased taxation on tobacco products is an effective method of
      reducing tobacco use. This study assessed population support among respondents
      aged >=15 years, from 27 European Union (EU) countries for increased taxation and
      other tobacco control measures during the 2009-2012 period. METHODS: Nationally
      representative data were obtained from the 2009 (n=26,788) and 2012 (n=26,751)
      cross-sectional Eurobarometer surveys. Estimates were compared using chi-square
      statistics. The effect of the relative change in gross domestic product (GDP) on
      the change in support for increased taxation during 2009-2012 was calculated
      using the Pearson correlation coefficient and linear regression models. RESULTS:
      Between 2009 and 2012, population support for increased taxes on tobacco products
      declined (56.1% to 53.2%; p<0.001). However, support for other tobacco control
      measures increased significantly. After adjusting for baseline GDP per capita
      (2009), a 10% increase in GDP per capita was associated with 4.5% increase in
      support of tax increases. When Latvia and Lithuania were excluded from the
      analyses (because of their marked deviation from the general trend), there was a
      strong correlation between the change in GDP and support for increased taxes
      (rho=0.64; p<0.001). Also, after adjusting for baseline GDP, support for higher
      taxes on tobacco increased by 7.0% for every 10% increase in GDP between 2009 and
      2012. CONCLUSIONS: Population support for tax increases declined in the EU
      between 2009 and 2012, especially in countries with declines in GDP nonetheless,
      public support for other tobacco control measures remains high, thus indicating a
      viable environment for more comprehensive tobacco control.

PMID- 25053467
TI  - Cardiovascular risk factors in 2011 and secular trends since 2007: the
      Cardiovascular Risk in Young Finns Study.
AB  - AIMS: Cardiovascular risk factor levels in 2011 and 4-year changes between 2007
      and 2011 were examined using data collected in follow-ups of the Cardiovascular
      Risk in Young Finns Study. METHODS: The study population comprised 2063 Finnish
      adults aged 34-49 years (45% male). Lipid and blood pressure levels, glucose and
      anthropometry were measured and life style risk factors examined with
      questionnaires. RESULTS: Mean total cholesterol level in 2011 was 5.19 mmol/l,
      low density lipoprotein (LDL)-cholesterol 3.27 mmol/l, high density lipoprotein
      (HDL)-cholesterol 1.33 mmol/l, and triglycerides 1.34 mmol/l. Using American
      Diabetes Association criteria, Type 2 diabetes (T2D) was observed in 4.1% and
      prediabetes (fasting glucose 5.6-6.9 mmol/l or glycated hemoglobin 5.7-6.4%)
      diagnosed for 33.8% of the participants. Significant changes (P < 0.05) between
      2007 and 2011 included an increase in waist circumference (3.3%) in women. In
      both sexes, systolic (-3.0% in women, -4.0% in men) and diastolic (-3.0% in
      women, -3.3% in men) blood pressure and triglycerides (-3.4% in women, -6.5% in
      men) decreased during follow-up. CONCLUSIONS: Previously observed favorable
      trends in ldl-cholesterol levels have leveled off among a sample of young and
      middle-aged adults in finland triglyceride and blood pressure levels have
      decreased over one-third of the study population had prediabetes and may be at
      increased risk for T2D:

PMID- 25053468
TI  - Self-reported musculoskeletal pain predicts long-term increase in general health
      care use: a population-based cohort study with 20-year follow-up.
AB  - AIMS: Musculoskeletal pain and disability is a modern epidemic and a major reason
      for seeking health care. The aim of this study is to determine absolute and
      relative rates of care seeking over 20 years for adults reporting musculoskeletal
      complaints. METHODS: Interview data on musculoskeletal pain reported during the
      past two weeks from the Danish National Cohort Study were merged with data from
      the Danish National Health Insurance Registry and the National Patient Registry
      containing information on consultations in the Danish primary and secondary care
      sector. Absolute and relative rates for all seeking of care with general
      practitioners, physiotherapists, chiropractors, outpatient hospital contacts and
      hospital admissions are reported for persons reporting no musculoskeletal pain
      and for persons reporting pain in the neck, shoulder, wrist/hands, mid back, low
      back, hips, knees and ankles/feet. RESULTS: Regardless of site, persons
      experiencing a musculoskeletal complaint had a statistically increased risk of
      consulting a general practitioner when compared with persons reporting no
      musculoskeletal complaint. For physiotherapists and chiropractors, only persons
      complaining of neck pain and back pain had an increased risk of seeking care.
      Regardless of pain site, except for shoulder pain, persons reporting
      musculoskeletal pain had a statistically significant increased risk of outpatient
      hospital consultations and hospital admissions. Few differences were found
      between pain sites in relation to any of the outcomes. CONCLUSIONS: Self-report
      of musculoskeletal pain reported within the past two weeks predicts a
      statistically significant long-term increase in general use of health care
      services in both the primary and the secondary health care sector.

PMID- 25053469
TI  - Vitamin D deficiency and lifestyle risk factors in a Norwegian adolescent
      population.
AB  - AIM: The aim was to study vitamin D status in a healthy adolescent Norwegian
      population at 69 degrees N. METHODS: The data presented come from The Tromso
      Study: Fit Futures, during the school year 2010/2011 (not including the summer
      months), where 1,038 (92% of those invited) participated. Physical examinations,
      questionnaires and blood samples were collected, and serum 25-hydroxyvitamin D
      (25(OH)D) were analyzed using LC-MS/MS. RESULTS: RESULTS are presented from 475
      boys and 415 girls (15-18 years old) with available blood samples. A total of
      60.2% had vitamin D deficiency or insufficiency (serum 25(OH)D <50 nmol/l), 16.5%
      were deficient (<25 nmol/l) and 1.6% had severe vitamin D deficiency (<12.5
      nmol/l). Only 12.4% had levels >75 nmol/l. A significant gender difference with a
      mean (SD) serum 25(OH)D level of 40.5 (20.5) nmol/l in boys and 54.2 (23.2)
      nmol/l in girls (p <0.01) was present. Furthermore, 51.3% of girls had levels >50
      nmol/l in comparison to 29.7% of boys (p <0.01). There was an inverse correlation
      between parathyroid hormone levels and 25(OH)D, rs= -0.30 (p<0.01). Explanatory
      factors that were significantly associated with serum 25(OH)D levels in
      multivariate models were use of snuff, consumption of vitamin D fortified milk,
      cod liver oil and vitamin/mineral supplements, physical activity, sunbathing
      holiday and use of solarium in boys, and vitamin/mineral supplements, physical
      activity, sunbathing holiday and use of solarium in girls . CONCLUSIONS: Vitamin
      D deficiency is prevalent during the school year among adolescents in northern
      Norway, particularly among boys.

PMID- 25053470
TI  - Group sequential tests for long-term survival comparisons.
AB  - Sometimes in clinical trials, the hazard rates are anticipated to be
      nonproportional, resulting in potentially crossing survival curves. In these
      cases, researchers are usually interested in which treatment has better long-term
      survival. The log-rank test and the weighted log-rank test may not be appropriate
      or efficient to use here, because they are sensitive to differences in survival
      at any time and don't just focus on long-term outcomes. Also in a prospective
      clinical trial, patients are entered sequentially over calendar time, so that
      group sequential designs may be considered for ethical, administrative and
      economic concerns. Here we develop group sequential methods for testing the null
      hypothesis that the survival curves are identical after a prespecified time
      point. Several classes of tests are considered, including an integrated
      difference in survival probabilities after this time point, and linear or
      quadratic combinations of two component test statistics (pointwise comparisons of
      survival at the time point and comparisons of hazard rates after the time point).
      We examine the type I errors, stopping probabilities, and powers of these tests
      through simulation studies under the null and different alternatives, and we
      apply them to a real bone marrow transplant clinical trial. 

PMID- 25053471
TI  - Evolution of illustrations in anatomy: a study from the classical period in
      Europe to modern times.
AB  - Illustrations constitute an essential element of learning anatomy in modern
      times. However it required a significant evolutionary process spread over
      centuries, for illustrations to achieve the present status in the subject of
      anatomy. This review article attempts to outline the evolutionary process by
      highlighting on the works of esteemed anatomists in a chronological manner.
      Available literature suggests that illustrations were not used in anatomy during
      the classical period when the subject was dominated by the descriptive text of
      Galen. Guido da Vigevano was first to use illustrations in anatomy during the
      Late Middle Ages and this concept developed further during the Renaissance period
      when Andreas Vesalius pioneered in illustrations becoming an indispensable tool
      in conveying anatomical details. Toward later stages of the Renaissance period,
      Fabricius ab Aquapendente endeavored to restrict dramatization of anatomical
      illustrations which was a prevalent trend in early Renaissance. During the 18th
      century, anatomical artwork was characterized by the individual styles of
      prominent anatomists leading to suppression of anatomical details. In the 19th
      century, Henry Gray used illustrations in his anatomical masterpiece that focused
      on depicting anatomical structures and were free from any artistic style. From
      early part of the 20th century medical images and photographs started to
      complement traditional handmade anatomical illustrations. Computer technology and
      advanced software systems played a key role in the evolution of anatomical
      illustrations during the late 20th century resulting in new generation 3D image
      datasets that are being used in the 21st century in innovative formats for
      teaching and learning anatomy.

PMID- 25053472
TI  - Outcomes of group-based treatment program with parental involvement for the
      management of childhood and adolescent obesity.
AB  - OBJECTIVE: An uncontrolled study was conducted to evaluate the effects of a group
      based program on weight control, metabolic profiles, and obesity-related
      complications in obese youth. METHODS: The program consisted of an initial in
      patient session and five group sessions, one, two, three, six, and nine months
      into the study, providing participants and their parents with information about
      the consequences of obesity and lifestyle modifications. The severity of obesity
      and obesity-related complications were evaluated at baseline and 12 months after
      the intervention. The participants' and their parents' perceptions of the program
      were assessed. RESULTS: Of the obese youth recruited (n=126), 115 completed the
      study. Their percentage weight for height and percentage body fat decreased
      significantly (both p<0.001), and their insulin resistance, lipid profiles, and
      transaminases levels improved (all p<0.01). The prevalence of prediabetes,
      dyslipidemia, and elevated transaminases decreased significantly (all p<0.05).
      The participants and their parents perceived the program as valuable. CONCLUSION:
      A group-based program is effective in managing childhood obesity, improving
      metabolic profiles, and alleviating certain obesity-related complications.
      PRACTICE IMPLICATIONS: A group-based program that provides education and raises
      the awareness of obese children and their parents about the consequences of
      obesity is an effective model for treating childhood obesity.

PMID- 25053473
TI  - Mastery and perceived autonomy support are correlates of Dutch diabetes patients'
      self-management and quality of life.
AB  - OBJECTIVE: The aim of this study was to assess the associations between type 2
      diabetes patients' mastery and perceived autonomy support and their self
      management skills and health-related quality of life (HRQOL). METHODS: A cross
      sectional questionnaire survey was conducted among 3352 patients with type 2
      diabetes. Key variables were assessed with validated questionnaires. RESULTS:
      Patients' mastery and perceived autonomy support correlated positively with their
      self-management skills (r=0.34, p<0.001; r=0.37, p<0.001) and HRQOL (r=0.37,
      p<0.001; r=0.15, p<0.001). In the linear regression analysis, mastery and
      perceived autonomy support were positive correlates of self-management
      (beta=0.23; p<0.001; beta=0.25; p<0.001). Patients with more physical or
      psychological complications had significantly lower scores on mastery, perceived
      autonomy support, self-management and HRQOL. CONCLUSION: Our results indicate the
      importance of mastery in relation to diabetes patients' perceived autonomy
      support, self-management skills and HRQOL. PRACTICE IMPLICATIONS: Since a greater
      sense of mastery is likely to increase patients' autonomous motivation to cope
      with their disease, interventions can aim to influence patients' motivational
      regulation. In addition, we confirmed the need for autonomy support to improve
      patients' self-management skills. Professionals can be trained to be autonomy
      supportive, which relates to person-centered approaches such as motivational
      interviewing (MI).

PMID- 25053474
TI  - Haematology patients and the Internet--the use of on-line health information and
      the impact on the patient-doctor relationship.
AB  - OBJECTIVE: Patients access on-line health information (OHI) to better understand
      their health. We aimed to determine which demographic factors influence OHI use.
      We also explored how OHI is used and subsequent implications to the patient
      doctor relationship. METHODS: We distributed a self-administered questionnaire to
      202 haematology out-patients. RESULTS: 62.3% used the internet and 54.3% used
      OHI. Higher education, (P<0.001, OR 34.62, 95% CI 5.20-230.66) and household
      incomes of L15000-25000 (P=0.023 OR 4.8 95% CI 1.236-18.59) were positively
      associated with OHI use. Those reassured after reading OHI had improved trust in
      their specialist (P<0.001, OR 52.1, 95% CI 12.3-221.1), improved confidence
      during consultations, (P<0.001, OR 23.0, 95% CI 2.8-188.2) and were improved
      decisions makers (P=0.008, OR 13.6, 95% CI 4.1-45.7). Those with increased trust
      in their haematologist also had improved confidence (P<0.001, OR 6.2, 95% CI 2.2
      17.3) and improved decision making ability (P<0.001, OR 13.6, 95% CI 4.7-39.4).
      74.6% of patients did not share OHI with their haematologist. CONCLUSIONS: Two
      thirds of participants were exposed directly or indirectly to OHI. OHI affects
      patients' view of their health and influences behaviour during consultations.
      PRACTICE IMPLICATIONS: Haematologists could facilitate patients using OHI by
      recommending high quality websites and act supportively when patients share OHI.

PMID- 25053475
TI  - Turing instabilities in prey-predator systems with dormancy of predators.
AB  - In this paper, we study the stationary and oscillatory Turing instabilities of a
      homogeneous equilibrium in prey-predator reaction-diffusion systems with dormant
      phase of predators. We propose a simple criterion which is useful in classifying
      these Turing instabilities. Moreover, numerical simulations reveal transient
      spatio-temporal complex patterns which are a mixture of spatially periodic steady
      states and traveling/standing waves. In this mixture, the steady part is the
      stable Turing pattern bifurcated primarily from the homogeneous equilibrium,
      while wave parts are unstable oscillatory solutions bifurcated secondarily from
      the same homogeneous equilibrium. Although our criterion does not exclude the
      occurrence of oscillatory Turing instability, we have not yet found stable
      traveling/standing waves due to oscillatory Turing instability in our
      simulations. These results suggest that dormancy of predators is not a generator
      but an enhancer of spatio-temporal Turing patterns in prey-predator reaction
      diffusion systems. 

PMID- 25053476
TI  - Alpha-terpineol promotes triterpenoid production of Antrodia cinnamomea in
      submerged culture.
AB  - Antrodia cinnamomea is a medicinal mushroom producing potent bioactive
      triterpenoids. However, triterpenoids of A. cinnamomea in submerged culture are
      much less than those in fruiting bodies. Here we evaluated effects of different
      extracts from a host-related species, Cinnamomum camphora, on the mycelial growth
      and triterpenoid production of A. cinnamomea in submerged culture. The hot water
      extract of the stem showed the strongest promotion of the mycelial growth. The
      petroleum ether extract of the stem (PES) (0.05 g L(-1)) showed the greatest
      stimulatory effect on content and production of triterpenoids. A total of 39
      compounds including terpenoids, phenolic and aromatic compounds were identified
      in the PES by GC-MS analysis. Furthermore, the effects of seven compounds
      contained in the PES on the mycelial growth and triterpenoid production of A.
      cinnamomea were evaluated. Among them, alpha-terpineol (0.5 mg L(-1)) showed the
      greatest stimulatory effect on the triterpenoid content (23.31 mg g(-1)) and
      triterpenoid production (91.33 mg L(-1)) of A. cinnamomea. Results of LC-MS
      analysis showed that alpha-terpineol (0.5 mg L(-1)) stimulated the syntheses of
      six triterpenoids in the mycelia of A. cinnamomea. This indicates that alpha
      terpineol can act as an elicitor for triterpenoid biosynthesis in A. cinnamomea.

PMID- 25053477
TI  - Introduction to Notch signaling.
AB  - Notch signaling is probably the most widely used intercellular communication
      pathway. The Notch mutant in the fruit fly Drosophila melanogaster was isolated
      about 100 years ago at the dawn of genetics. Since then, research on Notch and
      its related genes in flies, worms, mice, and human has led to the establishment
      of an evolutionarily conserved signaling pathway, the Notch signaling pathway. In
      the past few decades, molecular cloning of the Notch signaling components as well
      as genetic, cell biological, biochemical, structural, and bioinformatic
      approaches have uncovered the basic molecular logic of the pathway. In addition,
      genetic screens and systems approaches have led to the expansion of the list of
      genes that interact and fine-tune the pathway in a context specific manner.
      Furthermore, recent human genetic and genomic studies have led to the discovery
      that Notch plays a role in numerous diseases such as congenital disorders,
      stroke, and especially cancer. Pharmacological studies are actively pursuing key
      components of the pathway as drug targets for potential therapy. In this chapter,
      we will provide a brief historical overview of Notch signaling research and
      discuss the basic principles of Notch signaling, focusing on the unique features
      of this pathway when compared to other signaling pathways. Further studies to
      understand and manipulate Notch signaling in vivo in model organisms and in
      clinical settings will require a combination of a number of different approaches
      that are discussed throughout this book. 

PMID- 25053478
TI  - Genetic screens to identify new Notch pathway mutants in Drosophila.
AB  - Notch signaling controls a wide range of developmental processes, including
      proliferation, apoptosis, and cell fate specification during both development and
      adult tissue homeostasis. The functional versatility of the Notch signaling
      pathway is tightly linked with the complexity of its regulation in different
      cellular contexts. To unravel the complexity of Notch signaling, it is important
      to identify the different components of the Notch signaling pathway. A powerful
      strategy to accomplish this task is based on genetic screens. Given that the
      developmental context of signaling is important, these screens should be
      customized to specific cell populations or tissues. Here, I describe how to
      perform F1 clonal forward genetic screens in Drosophila to identify novel
      components of the Notch signaling pathway. These screens combine a classical EMS
      (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis
      via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid
      phenotypic screening within clones of mutant cells induced at specific
      developmental stages and in tissues of interest, bypassing the pleiotropic
      effects of isolated mutations. More importantly, since EMS mutations have been
      notoriously difficult to map to specific genes in the past, I briefly discuss
      mapping methods that allow rapid identification of the causative mutations. 

PMID- 25053479
TI  - Structure-function analysis of Drosophila Notch using genomic rescue transgenes.
AB  - One of the evolutionarily conserved posttranslational modifications of the Notch
      receptors is the addition of an O-linked glucose to epidermal growth factor-like
      (EGF) repeats with a specific consensus sequence by the protein O
      glucosyltransferase Rumi (POGLUT1 in human). Loss of rumi in flies results in a
      temperature-sensitive loss of Notch signaling. To demonstrate that the Notch
      receptor itself is the biologically relevant target of Rumi in flies, and to
      determine the role of the 18 Rumi target sites on Notch in regulating Notch
      signaling, we have performed an in vivo structure-function analysis of Drosophila
      Notch. In this chapter, we provide a detailed protocol for this analysis. To
      avoid the potential artifacts associated with overexpression of Notch and random
      insertion of transgenes, we have used recombineering and site-specific
      integration technologies, which have been adapted for usage in Drosophila in
      recent years. Using gene synthesis and site-directed mutagenesis, we generated a
      series of Notch genomic transgenes which harbor mutations in all or specific
      subsets of Notch O-glucose sites. Gene dosage and rescue experiments in animals
      raised at various temperatures allowed us to dissect the contribution of O
      glucosylation sites to the regulation of the Notch signaling strength. The
      reagents and methods presented here can be used to address similar questions
      about other posttranslational modifications of Notch or other Drosophila
      proteins. 

PMID- 25053481
TI  - Immunohistochemical tools and techniques to visualize Notch in Drosophila
      melanogaster.
AB  - The ability to accurately visualize proteins in Drosophila tissues is critical
      for studying their abundance and localization relative to the morphology of cells
      during tissue development and homeostasis. Here we describe the procedure to
      visualize Notch localization in whole-mount preparations of several Drosophila
      organs using confocal microscopy. The use of monoclonal antibodies directed to
      distinct portions of Notch allows one to follow the fate of the receptor during
      constitutive and inductive processes. The protocol described here can be used to
      co-label with antibodies recognizing markers of subcellular compartments in wild
      type as well as mutant tissues. 

PMID- 25053482
TI  - Antibody uptake assay and in vivo imaging to study intracellular trafficking of
      Notch and Delta in Drosophila.
AB  - Notch signaling depends on regulated intracellular trafficking of the receptor
      and its ligands (Kopan and Ilagan, Cell 137:216-233, 2009; Le Borgne et al.,
      Development 132:1751-1762, 2005). Here we describe two methods to study the
      intracellular trafficking of Notch and Delta in Drosophila. First, an ex vivo
      antibody uptake assay is used to monitor endocytosis of Notch and Delta by living
      cells in dissected explants (Le Borgne and Schweisguth, Dev Cell 5:139-148,
      2003). Second, real-time imaging of fluorescent proteins that are expressed at
      physiological levels is used to study trafficking of Notch in living flies
      (Venken et al., Science 314:1747-1751, 2006; Couturier et al., Nat Cell Biol 14,
      131-139, 2012). 

PMID- 25053480
TI  - Overview of genetic tools and techniques to study Notch signaling in mice.
AB  - Aberrations of Notch signaling in humans cause both congenital and acquired
      defects and cancers. Genetically engineered mice provide the most efficient and
      cost-effective models to study Notch signaling in a mammalian system. Here, we
      review the various types of genetic models, tools, and strategies to study Notch
      signaling in mice, and provide examples of their use. We also provide advice on
      breeding strategies for conditional mutant mice, and a protocol for tamoxifen
      administration to mouse strains expressing inducible Cre recombinase-estrogen
      receptor fusion proteins. 

PMID- 25053483
TI  - Tracking trafficking of Notch and its ligands in mammalian cells.
AB  - The Notch receptor and its ligands are cell surface transmembrane proteins that
      are internalized. Endocytosis and vesicle trafficking play key roles in Notch
      signaling activation and modulation. In mammalian cultured cells it is possible
      to track these cell surface molecules by pulse-labeling these proteins in vivo.
      One labeling protocol consists in the covalent linkage of membrane-impermeable
      biotin followed by western blotting. An alternative protocol consists of using
      high affinity antibodies against the extracellular domains of the proteins
      followed by immunofluorescence, thereby allowing monitoring of the fate of the
      labeled proteins. In this chapter, we will describe these two approaches to study
      the dynamics of receptor and ligand trafficking. 

PMID- 25053484
TI  - Visualizing Notch signaling in vivo in Drosophila tissues.
AB  - The ability to visualize Notch pathway activity in vivo is invaluable for
      studying the functions and mechanisms of Notch signaling. A variety of tools have
      been developed to enable monitoring of pathway activity in Drosophila, including
      endogenous Notch-responsive genes and synthetic transcriptional reporter
      constructs. Here we summarize some of the different Notch signaling reporters
      that are available, discuss their relative merits, and describe two methods for
      visualizing their expression (immunostaining and X-gal staining). These
      approaches are widely applicable to a range of tissues and stages in Drosophila
      development. 

PMID- 25053485
TI  - Monitoring Notch activity in the mouse.
AB  - Several laboratories have developed genetic methods to monitor Notch activity in
      developing and adult mice. These approaches have been useful in identifying Notch
      signaling with high temporal and spatial resolution. This research has
      contributed substantially to our understanding of the role of Notch in cell
      specification and cellular physiology. Here, we present two protocols to monitor
      Notch activity in the mouse brain: (1) by intraventricular electroporation and
      (2) by intracranial viral injections of Notch reporter constructs. These methods
      allow monitoring of Notch signaling in specific brain regions from development to
      adulthood. In addition, using the appropriate modifications, the Notch reporter
      systems can also be used to monitor Notch activity in other organs of the mouse
      such as retina, skin, skeletal muscle, and cancer cells. 

PMID- 25053486
TI  - Notch signaling assays in Drosophila cultured cell lines.
AB  - Signaling assays in Drosophila cell lines are a valuable method for investigating
      whether other proteins influence the function of the Notch pathway and for
      assessing whether specific enhancers or genes are regulated by Notch. In this
      chapter, we will describe two different types of assays that can be used to
      monitor Notch activation in Kc167 and S2 cells. One involves activating Notch in
      cultured cells and measuring the change in endogenous gene expression levels. The
      other uses luciferase reporters and measures their response to Notch, by co
      transfecting with NICD. 

PMID- 25053487
TI  - Monitoring Notch activation in cultured mammalian cells: transcriptional reporter
      assays.
AB  - Upon ligand binding, Notch activation and cleavage culminates in the expression
      of its target genes. Hence, the use of Notch-responsive promoters to drive
      reporter gene expression provides a flexible and robust approach for monitoring
      signaling activity. In this chapter, we present an overview of Notch
      transcriptional reporter assays and discuss different methods for ligand
      independent and ligand-dependent activation of Notch in mammalian cells. 

PMID- 25053488
TI  - Monitoring Notch activation in cultured mammalian cells: luciferase
      complementation imaging assays.
AB  - Notch activation and cleavage releases the Notch intracellular domain (NICD),
      which translocates to the nucleus, where it associates with its DNA-binding
      partner CSL to recruit the coactivator MAML and additional cofactors to
      ultimately activate target gene expression. Taking advantage of the specific
      interaction between NICD and these factors, we have developed a luciferase
      complementation imaging (LCI)-based reporter system to quantitatively monitor
      Notch activation in real time in live cells. In this chapter, we describe the use
      of Notch LCI reporters for measuring protein interactions and performing detailed
      kinetic analyses of receptor activation and its responses to various stimuli. 

PMID- 25053489
TI  - Visualization of Notch signaling oscillation in cells and tissues.
AB  - The Notch signaling effectors Hes1 and Hes7 exhibit oscillatory expression with a
      period of about 2-3 h during embryogenesis. Hes1 oscillation is important for
      proliferation and differentiation of neural stem cells, whereas Hes7 oscillation
      regulates periodic formation of somites. Continuous expression of Hes1 and Hes7
      inhibits these developmental processes. Thus, expression dynamics are very
      important for gene functions, but it is difficult to distinguish between
      oscillatory and persistent expression by conventional methods such as in situ
      hybridization and immunostaining. Here, we describe time-lapse imaging methods
      using destabilized luciferase reporters and a highly sensitive cooled charge
      coupled device camera, which can monitor dynamic gene expression. Furthermore,
      the expression of two genes can be examined simultaneously by a dual reporter
      system using two-color luciferase reporters. Time-lapse imaging analyses reveal
      how dynamically gene expression changes in many biological events. 

PMID- 25053490
TI  - Proteomic analysis of the Notch interactome.
AB  - Recent large-scale studies have provided a global description of the interactome
      the whole network of protein interactions in a cell or an organism-for several
      model organisms. Defining protein interactions on a proteome-wide scale has led
      to a better understanding of the cellular functions of many proteins, especially
      those that have not been studied by classical molecular genetic approaches. Here
      we describe the resources, methods, and techniques necessary for generation of
      such a proteome-scale interactome in a high throughput manner. These procedures
      will also be applicable to low or medium throughput focused studies aimed at
      understanding interactions between members of specific pathways such as Notch
      signaling. 

PMID- 25053491
TI  - Bacterial expression and in vitro refolding of limited fragments of the Notch
      receptor and its ligands.
AB  - Prokaryotic expression of limited fragments of the Notch receptor and its ligands
      followed by in vitro refolding has been used for the production of the
      significant amounts of protein required for structure determination by X-ray
      crystallography or nuclear magnetic resonance spectroscopy. As an illustration of
      the protocol for the production of these EGF-containing constructs we have
      focused on a limited fragment of human Notch 1 that contains three calcium
      binding EGF domains, hNotch-111-13. Following characterization by the methods
      described here, this construct has been shown to be functionally competent in a
      range of assays and the structure has been solved by X-ray crystallography and
      NMR. 

PMID- 25053492
TI  - Analyzing the posttranslational modification status of Notch using mass
      spectrometry.
AB  - Notch is modified by multiple types of posttranslational modifications, most of
      which are known to affect Notch function. The extracellular domain (ECD) is
      modified with N-glycosylation and at least three types of O-glycosylation (O
      fucose, O-glucose, and O-GlcNAc), while the intracellular domain is hydroxylated,
      phosphorylated, and ubiquitinated. In order to analyze the structure and function
      of the O-glycans decorating the ECD, we have developed semiquantitative mass
      spectral methods for identifying modifications at individual sites on Notch that
      are generally applicable to most posttranslational modifications. Here we
      describe the expression and purification of Notch ECD fragments, digestion of the
      fragments with proteases to prepare for mass spectral analysis, and
      identification of peptides modified with O-glycans using mass spectrometry. 

PMID- 25053493
TI  - Assay to probe proteolytic processing of Notch by gamma-secretase.
AB  - With the increasing appreciation of the role of Notch in development and disease,
      measuring its cleavage and signaling activity in cellular systems has become
      important. Here we describe a cell-based method to analyze the cleavage of Notch
      at the S3 site by gamma-secretase. HEK cells are transfected with an N-terminal
      truncated and myc-labeled mNotchDeltaE construct which can be easily and
      quantitatively detected by western blotting. 

PMID- 25053494
TI  - Analyzing the nuclear complexes of Notch signaling by electrophoretic mobility
      shift assay.
AB  - An electrophoretic mobility shift assay (EMSA) is a sensitive technique for
      detecting protein-DNA and protein-protein interactions in which complexes are
      separated by native (non-denaturing) gel electrophoresis. EMSAs can provide
      evidence for specific binding between components prepared from a wide range of
      sources, including not only highly purified proteins but also components of crude
      cellular extracts. EMSA experiments were critical in identifying the minimal
      protein requirements for assembly of transcriptionally active nuclear Notch
      complexes as well as the DNA sequence specificity of Notch transcription
      complexes. Here, we describe a radioactive EMSA protocol for detection of Notch
      transcription complexes. 

PMID- 25053495
TI  - Identifying direct Notch transcriptional targets using the GSI-washout assay.
AB  - Genetic gain- and loss-of-function studies have traditionally been used to study
      transcriptional networks regulated by the Notch signaling pathway; however these
      techniques lack the ability to resolve primary and secondary transcriptional
      events. In contrast, the gamma-secretase inhibitor (GSI) washout assay takes
      advantage of the reversibility of GSI, a pharmacological inhibitor of Notch
      signaling, along with the ability of cycloheximide to prevent secondary
      transcriptional effects to identify direct Notch pathway targets. Here we review
      this technique and the technical considerations for adapting this assay to a cell
      type of choice. 

PMID- 25053496
TI  - Probing the epigenetic status at Notch target genes.
AB  - Chromatin-based mechanisms significantly contribute to the regulation of many
      developmentally regulated genes, including Notch target genes. After specific
      ligand binding, the intracellular part of the Notch receptor is cleaved off and
      translocates to the nucleus, where it binds to the transcription factor CSL
      (encoded by the RBPJ gene in mammals), in order to activate transcription. In the
      absence of a Notch signal, CSL represses Notch target genes by recruiting a co
      repressor complex. Both NICD co-activator and CSL co-repressor complexes contain
      chromatin modifiers such as histone acetyltransferases and methyltransferases,
      which dynamically regulate chromatin marks at Notch target genes. Here we provide
      protocols for ChIP (chromatin immunoprecipitation) to analyze the chromatin
      status of dynamically regulated Notch target genes. Furthermore, an example is
      presented how to perform a primary analysis of ChIP-Seq data at Notch target
      genes using the Cistrome platform.

PMID- 25053497
TI  - Notch-ligand binding assays in Drosophila cells.
AB  - Activation of the Drosophila transmembrane receptor protein Notch is induced by
      association with its transmembrane ligands, Delta and Serrate. The ability to
      assay binding between Notch and its ligands has been essential for characterizing
      the influence of posttranslational modifications, such as glycosylation, as well
      as for characterizing structural motifs involved in receptor-ligand interactions.
      We describe here a simple, widely used method for assaying receptor-ligand
      binding. This method involves expression of soluble forms of either Notch or its
      ligands, comprising the extracellular domains fused to an easily assayed tag, the
      enzyme alkaline phosphatase. These soluble proteins are then incubated with their
      binding partners, either as transmembrane proteins expressed on the surface of
      cultured cells or as extracellular protein domains attached to agarose beads.
      After washing, the amount of bound protein can be readily assayed by measuring
      alkaline phosphatase activity. 

PMID- 25053498
TI  - Modeling Notch signaling: a practical tutorial.
AB  - Theoretical and computational approaches for understanding different aspects of
      Notch signaling and Notch dependent patterning are gaining popularity in recent
      years. These in silico methodologies can provide dynamic insights that are often
      not intuitive and may help guide experiments aimed at elucidating these
      processes. This chapter is an introductory tutorial intended to allow someone
      with basic mathematical and computational knowledge to explore new mathematical
      models of Notch-mediated processes and perform numerical simulations of these
      models. In particular, we explain how to define and simulate models of lateral
      inhibition patterning processes. We provide a Matlab code for simulating various
      lateral inhibition models in a simple and intuitive manner, and show how to
      present the results from the computational models. This code can be used as a
      starting point for exploring more specific models that include additional aspects
      of the Notch pathway and its regulation. 

PMID- 25053499
TI  - Small molecules that inhibit Notch signaling.
AB  - The proteolytic processing of Notch receptors plays a central role in the
      transduction of Notch signaling, which is involved in a variety of important
      processes in the body. Abnormal Notch processing has been implicated in a variety
      of cancers. gamma-Secretase is responsible for the third and last cleavage step
      of Notch receptors. Since gamma-secretase plays an important role in Alzheimer's
      disease, great effort has been spent to develop gamma-secretase inhibitors
      (GSIs). The majority of these inhibitors block gamma-secretase nonselectively,
      which means that these compounds can be used to block Notch cleavage and thereby
      regulate Notch signaling. In this review we give an overview of the most-used
      GSIs in the Notch field, together with examples of their use. It is a huge
      advantage that these drug-like compounds are already optimized for gamma
      secretase, and some are already being used in clinical trials. However, their
      nonspecificity has disadvantages as well, since four Notch receptors exist with
      different sites of expression and different roles in cell signaling and at least
      four different gamma-secretase proteases are involved in their cleavage. It would
      be worth the effort to screen many GSIs for their selectivity for the different
      Notch receptors and gamma-secretases, in order to obtain interesting tools for
      further research and-in the end-to develop safer drugs. 

PMID- 25053500
TI  - Application and evaluation of anti-Notch antibodies to modulate Notch signaling.
AB  - In recent years, several groups have reported the development of antibodies that
      inhibit or activate Notch signaling. Modulatory antibodies are valuable
      experimental tools that permit specific targeting of individual Notch receptor
      homologs (in contrast to pan-Notch-receptor inhibitors like gamma-secretase
      inhibitors), and show promise as therapeutic agents. Typically, Notch responsive
      luciferase reporter assays are used to validate and characterize modulatory
      antibodies. We describe detailed methods for performing dual luciferase-based
      signaling assays to read out modulation of Notch activity by antibodies designed
      to inhibit/activate signaling. 

PMID- 25053501
TI  - Application of anti-ligand antibodies to inhibit Notch signaling.
AB  - Emerging evidence suggests that Notch signaling not only regulates biological
      processes during development but also participates in the pathogenesis of various
      diseases in adults, including tumor angiogenesis, hematopoietic malignancies, and
      cardiometabolic syndromes. Notch signaling involves several ligands and receptors
      that have unique and overlapping functions. Therefore, blocking function of a
      ligand or receptor with a neutralizing antibody is a useful approach to examine
      the specific role of each Notch component. In addition, administration of Notch
      signaling blocking antibodies in experimental animals offers important insights
      into clinical translation of Notch biology. In this chapter, we describe examples
      of in vitro and in vivo loss-of-function experiments with blockade of Notch
      ligands, particularly Delta-like ligand 4 (Dll4). 

PMID- 25053502
TI  - Sequence-based characterization of five SLA loci in Asian wild boars.
AB  - Two swine leucocyte antigen (SLA) class I (SLA-1 and SLA-2) and three class II
      (DRB1, DQB1 and DQA) genes were investigated for their diversity in Asian wild
      boars using a sequence-based typing method. A total of 15 alleles were detected
      at these loci, with eleven being novel. The findings provide one of the first
      glimpses of the SLA allelic diversity and architecture in the wild boar
      populations. 

PMID- 25053503
TI  - New reagents for detecting free radicals and oxidative stress.
AB  - Free radicals and oxidative stress play important roles in the deterioration of
      materials, and free radicals are important intermediates in many biological
      processes. The ability to detect these reactive species is a key step on the road
      to their understanding and ultimate control. This short review highlights recent
      progress in the development of reagents for the detection of free radicals and
      reactive oxygen species with broad application to materials science as well as
      biology. 

PMID- 25053504
TI  - Redirection of CD4+ and CD8+ T lymphocytes via a novel antibody-based modular
      targeting system triggers efficient killing of PSCA+ prostate tumor cells.
AB  - BACKGROUND: There is still a need for new therapeutic options against prostate
      cancer. Conventional single-chain bispecific antibodies (bsAbs), that directly
      cross-link T cells and tumor cells, hold great potential for efficient tumor
      treatment. However, rapid development of novel bsAbs is hampered by laborious
      optimization to improve their efficacy and reduce potential side effects. To
      accelerate the development of a novel antibody tool for the redirection of T
      cells to different tumor-associated antigens, we recently introduced a modular
      targeting system. METHODS: We here describe a novel modular system for treatment
      of prostate cancer by retargeting of T cells to the prostate stem cell antigen
      (PSCA). Functionality of the novel PSCA-specific modular system was investigated
      in vitro by T cell activation and chromium release assays as well as in
      immunodeficient mice. RESULTS: Similar to a conventional bsAb CD3-PSCA, the novel
      PSCA-specific modular system induces activation of both CD4+ and CD8+ T cells
      leading to secretion of pro-inflammatory cytokines and highly efficient target
      specific tumor cell lysis. The novel TM was ready-to-use from the time point of
      construction and functional at low E:T ratios and picomolar concentrations
      without further optimization. In addition, the PSCA-specific modular system
      delays outgrowth of s.c. tumors in mice comparable to bsAb CD3-PSCA. CONCLUSIONS:
      We have developed a novel PSCA-specific modular system which triggers an
      efficient T cell-mediated killing of PSCA+ tumor cells in vitro and in vivo. The
      new Ab-based targeting strategy can functionally replace conventional bsAbs and
      allows a flexible redirection of T cells to different tumor-associated antigens.

PMID- 25053505
TI  - Subchronic stimulation performance of transverse intrafascicular multichannel
      electrodes in the median nerve of the Gottingen minipig.
AB  - This work evaluated the subchronic stimulation performance of an intraneural
      multichannel electrode (transverse intrafascicular multichannel electrode, TIME)
      in a large human-sized nerve. One or two TIMEs were implanted in the right median
      nerve above the elbow joint in four pigs for a period of 32 to 37 days (six TIMEs
      in total). The ability of the contact sites to recruit five muscles in the
      forelimb was assessed via their evoked electromyographic responses. Based on
      these responses, a selectivity index was defined. Four TIMEs were able to
      selectively recruit a subset of muscles throughout the implantation period. The
      required recruitment current significantly increased, while there was a tendency
      for the recruitment selectivity to decrease over time. Histological assessment
      showed that all TIMEs remained inside the nerve and that they were located
      between fascicles. The average thickness of the encapsulation of the electrode
      was estimated to be 115.4 +/- 51.5 MUm (mean +/- SD). This study demonstrates the
      feasibility of keeping the TIME electrodes fixed and functional inside a large
      polyfascicular human-sized nerve in a subchronic setting. 

PMID- 25053506
TI  - Current treatment of head and neck squamous cell cancer.
AB  - Head and neck cancer is a heterogenous group of cancers involving the upper
      aerodigestive tract. In this review article, the most common sites will be
      discussed, including the oral cavity, oropharynx, hypopharynx, and larynx.
      Etiology and epidemiology will be discussed followed by staging, treatment, and
      survival.

PMID- 25053507
TI  - Challenges of nurses' deployment to other New York City hospitals in the
      aftermath of Hurricane Sandy.
AB  - On October 29, 2012, a 12-ft storm surge generated by Hurricane Sandy
      necessitated evacuation and temporary closure of three New York City hospitals
      including NYU Langone Medical Center (NYULMC). NYULMC nurses participated in the
      evacuation, and 71 % were subsequently deployed to area hospitals to address
      patient surge for periods from a few days up to 2 months when NYULMC reopened.
      This mixed methods study explored nurses' experience in the immediate disaster
      and the subsequent deployment. More than 50 % of deployed nurse participants
      reported the experience to be extremely or very stressful. Deployed nurses
      encountered practice challenges related to working in an unfamiliar environment,
      limited orientation, legal concerns about clinical assignments. They experienced
      psychosocial challenges associated with the intense experience of the evacuation,
      uncertainty about future employment, and the increased demands of managing the
      deployment. Findings provide data to inform national and regional policies to
      support nurses in future deployments.

PMID- 25053508
TI  - A pilot randomised controlled trial evaluating postoperative packing of the
      perianal abscess.
AB  - PURPOSE: Traditional management of a perianal abscess involves incision and
      drainage followed by packing of the cavity until healing by secondary intention
      is complete. The evidence supporting this is lacking however, and regular
      postoperative packing is time-consuming, painful and costly. This pilot study
      aimed to assess whether healing could be achieved safely without packing and to
      obtain preliminary results to enable sample size calculation in order to
      facilitate the implementation of a large multicentre randomised controlled trial.
      ClinicalTrials.gov Identifier: NCT01853267. METHODS: Fourteen patients with
      perianal abscesses were randomised to packing or non-packing of the abscess
      cavity postoperatively. Outcome measures were time to healing, abscess
      recurrence, fistula formation and postoperative pain. RESULTS: Healing in the non
      packing group was faster compared to the packing group: mean 26.8 days (95 %
      confidence interval 22.7 to 30.7) vs 19.5 days (13.6 to 25.4); P = 0.047. There
      were no differences in recurrence rates between the groups (37.5 % packing group
      vs 33.3 % non-packing group; P = 0.580) at a median follow-up of 90.0 weeks
      (interquartile range (IQR) 26.0). In patients presenting with recurrence, one
      fistula was found in the packing group with no fistulas in the non-packing group.
      The non-packing group reported less pain 2 weeks postoperatively: median (IQR)
      2.00 (3.00) vs 0.00 (1.00); (P = 0.030). CONCLUSION: Within the limitations of a
      small sample population, the results of this pilot study suggest that not packing
      the perianal abscess cavity after incision and drainage is safe. Our results show
      not packing confers less pain with a faster healing time compared with the
      conventional packing method, and this is a novel finding. These results need to
      be corroborated in the setting of a larger multicentre randomised controlled
      trial.

PMID- 25053510
TI  - Time, the great physician.

PMID- 25053509
TI  - Soluble MHC-II proteins promote suppressive activity in CD4+ T cells.
AB  - Soluble MHCII (sMHCII) molecules are present in body fluids of healthy
      individuals and are considered to be involved in the maintenance of self
      tolerance, and are also related to various diseases. Their concentration
      increases during in vivo antigen-specific tolerogenic stimulation and it was
      recently shown that exosome-mediated tolerance is MHCII dependent. At the
      cellular level, sMHCII proteins compete with membrane MHCII for T-cell receptor
      binding on CD4(+) T cells. Immunoaffinity purification techniques isolated sMHCII
      antigens from the serum of human serum albumin (HSA) -tolerant mice as a single
      highly glycosylated protein of ~ 60,000 molecular weight, specifically
      interacting with anti-class II antibodies in Western blotting and ELISA. Mass
      spectroscopy showed that these sMHCII proteins were loaded with the tolerogenic
      peptide as well as multiple self peptides. At the cellular level, sMHCII
      suppressed antigen-specific, and to a lesser degree antigen-non-specific, spleen
      cell proliferation and induced CD25 in naive T cells. In T cells activated by
      antigen-seeded macrophages, sMHCII decreased CD28 and increased CTLA-4 protein
      expression, while decreasing interleukin-2 and increasing interleukin-10
      production. In this case, sMHCII proteins were shown to decrease ZAP-70 and LAT
      phosphorylation. The results presented here for the first time provide evidence
      for the role of sMHCII proteins in immune response suppression and maintenance of
      tolerance, revealing novel regulatory mechanisms for immune system manipulation.

PMID- 25053511
TI  - Preventing vision loss from advanced age-related macular degeneration.

PMID- 25053512
TI  - Screening of a new cadmium hyperaccumulator, Galinsoga parviflora, from winter
      farmland weeds using the artificially high soil cadmium concentration method.
AB  - A new method, the artificially high soil cadmium (Cd) concentration method, was
      used to screen for Cd hyperaccumulators among winter farmland weeds. Galinsoga
      parviflora was the most promising remedial plant among 5 Cd accumulators or
      hyperaccumulators. In Cd concentration gradient experiments, as soil Cd
      concentration increased, root and shoot biomass decreased, and their Cd contents
      increased. In additional concentration gradient experiments, superoxide dismutase
      and peroxidase activities increased with soil Cd concentrations up to 75 mg kg(
      1) , while expression of their isoenzymes strengthened. Catalase (CAT) activity
      declined and CAT isoenzyme expression weakened at soil Cd concentrations less
      than 50 mg kg(-1) . The maxima of Cd contents in shoots and roots were 137.63 mg
      kg(-1) and 105.70 mg kg(-1) , respectively, at 100 mg kg(-1) Cd in soil. The root
      and shoot bioconcentration factors exceeded 1.0, as did the translocation factor.
      In a field experiment, total extraction of Cd by shoots was 1.35 mg m(-2) to 1.43
      mg m(-2) at soil Cd levels of 2.04 mg kg(-1) to 2.89 mg kg(-1) . Therefore, the
      artificially high soil Cd concentration method was effective for screening Cd
      hyperaccumulators. Galinsoga parviflora is a Cd hyperaccumulator that could be
      used to efficiently remediate Cd-contaminated farmland soil.

PMID- 25053513
TI  - Differential nuclear shape dynamics of invasive andnon-invasive breast cancer
      cells are associated with actin cytoskeleton organization and stability.
AB  - Cancer cells often exhibit characteristic aberrations in their nuclear
      architecture, which are indicative of their malignant potential. In this study,
      we have examined the nuclear and cytoskeletal composition, attachment
      configuration dynamics, and osmotic or drug treatment response of invasive
      (Hs578T and MDA-MB-231) and non-invasive (MCF-10A and MCF-7) breast cancer cell
      lines. Unlike MCF-10A and MCF-7, Hs578T and MDA-MB-231 cells showed extensive
      nuclear elasticity and deformability and displayed distinct kinetic profiles
      during substrate attachment. The nuclear shape of MCF-10A and MCF-7 cells
      remained almost unaffected upon detachment, hyperosmotic shock, or cytoskeleton
      depolymerization, while Hs578T and MDA-MB-231 revealed dramatic nuclear contour
      malformations following actin reorganization. 

PMID- 25053514
TI  - Substantial iodine volume load reduction in CT angiography with dual-energy
      imaging: insights from a pilot randomized study.
AB  - We explored whether dual-energy computed tomography (DECT) can allow a
      significant reduction in iodinated contrast volume during computed tomography
      angiography (CTA) without hampering image quality or assessibility. We
      prospectively randomized patients clinically referred to CTA to single energy
      computed tomography (SECT) with full iodine volume load (group A), DECT with 50 %
      iodine volume load (group B), DECT with 40 % iodine volume load (group C), and
      DECT with 30 % iodine volume load (group D); and compared image quality and
      assessibility. Eighty patients were enrolled and prospectively randomized. The
      mean age was 61.7 +/- 15.0 years and 56 (71 %) patients were male. The
      demographical characteristics, body mass index, or mean radiation dose did not
      differ between groups. Significant reductions in total contrast volume were
      achieved in groups B, C, and D; with mean administrated contrast volumes of 90.3
      +/- 10.1, 39.5 +/- 4.6, 28.3 +/- 6.5, and 23.9 +/- 6.0 mL, respectively, in
      groups A to D (p < 0.0001). With regard to image quality, no significant decrease
      in the Likert scale was observed with reductions of up to 60 % of the contrast
      volume (groups B and C). DECT at 50-60 keV in association with up to 60 % iodine
      load reduction, allowed similar signal density, image noise, and signal to noise
      ratio that SECT imaging with full iodine load. In this pilot, prospective,
      randomized study, dual energy CTA with up to 60 % iodine volume load reduction
      provided similar image quality and assessibility than full iodine load with
      conventional SECT imaging.

PMID- 25053515
TI  - Predictors of coronary artery aneurysm after stent implantation in patients with
      ST-segment elevation myocardial infarction treated with primary percutaneous
      coronary intervention.
AB  - The clinical and angiographic predictors of coronary artery aneurysm (CAA)
      formation in patients with ST-segment elevation acute myocardial infarction
      (STEMI) undergoing primary percutaneous coronary intervention (PCI) are not
      clear. This study aims to assess the predictors of CAA formation after primary
      PCI. 3,428 patients who underwent PCI for STEMI were enrolled. The average period
      of follow-up was mean 48 months (range 35-56 months) after PCI. During this time,
      1,304 patients were underwent follow-up coronary angiography. CAA was detected in
      21 patients (1.6 %). CAA occurred at the segment of stent implantation in all
      patients. The clinical and angiographic data were compared between patients with
      CAA group (n = 21) and without CAA group (n = 1,283). Patients who developed CAA
      had longer reperfusion time, higher high-sensitiviy C-reactive protein (hs-CRP)
      levels and neutrophil to lymphocyte ratio than those who had without CAA.
      Angiographically, CAA developed proximally located lesions and lesion length was
      significantly greater in patients with CAA than without CAA. Statin and beta
      blocker discontinuation were found higher in stent-associated CAA. Every 1 mg/l
      increase in hs-CRP and implantation of drug eluting stent (DES) were independent
      predictor of CAA formation after STEMI. Baseline elevated inflammation status and
      DES implantation in the setting of STEMI may predict the CAA formation.

PMID- 25053516
TI  - Cyclin D1, p16(INK) (4A) and p27(Kip1) in pancreatic adenocarcinoma: assessing
      prognostic implications through quantitative image analysis.
AB  - The prognostic significance of cyclin D1, p16(INK) (4A) and p27(Kip1) expression
      has been documented in several human malignancies; however, their prognostic
      potential in pancreatic adenocarcinoma is still unclear. This study aimed to
      assess the correlation of the aforementioned molecules with clinicopathological
      parameters and prognosis. Sixty patients with pancreatic ductal adenocarcinoma
      underwent surgical resection at a single institution; immunohistochemical
      staining of the studied markers was quantified by Iotamage analysis system.
      Cyclin D1 overexpression was positively associated with grade, neural
      infiltration and vascular invasion, whereas p27 positively correlated with age.
      Higher cyclin D1 expression indicated poorer survival (adjusted HR = 9.75, 95%CI:
      1.48-64.31, p = 0.018, increment: one unit in H-score), whereas a marginal trend
      toward an association between p16 positivity and improved survival was observed
      (adjusted HR = 0.58, 95%CI: 0.32-1.05, p = 0.072 regarding positive vs negative
      cases). No significant association with overall survival was noted regarding p27.
      In conclusion, cyclin D1 overexpression and possibly p16 loss of expression in
      pancreatic adenocarcinoma seem to be adverse prognostic factors, whereas p27
      expression did not seem to possess such prognostic properties. Further validation
      of the present findings in studies encompassing larger samples seems to be
      needed.

PMID- 25053518
TI  - Aerial radiation monitoring around the Fukushima Dai-ichi Nuclear Power Plant
      using an unmanned helicopter.
AB  - The Great East Japan Earthquake on March 11, 2011 generated a series of large
      tsunami that seriously damaged the Fukushima Dai-ichi Nuclear Power Plant
      (FDNPP), which resulted in the release of radioactive materials into the
      environment. To provide further details regarding the distribution of air dose
      rate and the distribution of radioactive cesium ((134)Cs and (137)Cs) deposition
      on the ground within a radius of approximately 5 km from the nuclear power plant,
      we carried out measurements using an unmanned helicopter equipped with a
      radiation detection system. The distribution of the air dose rate at a height of
      1 m above the ground and the radioactive cesium deposition on the ground was
      calculated. Accordingly, the footprint of radioactive plumes that extended from
      the FDNPP was illustrated. 

PMID- 25053517
TI  - A novel small-molecule activator of procaspase-3 induces apoptosis in cancer
      cells and reduces tumor growth in human breast, liver and gallbladder cancer
      xenografts.
AB  - PURPOSE: Procaspase-3, a proenzyme of apoptotic executioner caspase-3, is
      overexpressed in numerous tumors. We aimed to characterize a novel procaspase-3
      activator, WF-210, which may have potential as an anticancer drug. EXPERIMENTAL
      DESIGN: The procaspase-3 activating ability, antitumor efficacy, mechanisms of
      action, and toxicity profiles of WF-210 were investigated in vitro and in vivo,
      using normal cells, cancer cells, and mouse xenograft models. The role of
      procaspase-3 in WF-210-induced apoptosis was explored by manipulating procaspase
      3 expression in cultured cells. RESULTS: WF-210 activated procaspase-3 with an
      EC50 of 0.95 MUM, less than half that of its mother compound PAC-1 (2.08 MUM).
      The mechanism involved the chelation of inhibitory zinc ions, subsequently
      resulting in an auto-activation of procaspase-3. WF-210 was more cytotoxic than
      PAC-1 to human cancer cells, but less cytotoxic to normal cells. Cancer cells
      with high procaspase-3 expression, like HL-60 and U-937, were particularly
      sensitive. WF-210-induced the apoptosis of HL-60 and U-937 cells by activating
      procaspases and promoting proteasome-dependent degradation of XIAP and Survivin.
      The level of WF-210-induced apoptosis in cultured cells was related to the level
      of procaspase-3 expression. Finally, WF-210 was superior to PAC-1 in retarding
      the in vivo growth of breast, liver and gallbladder xenograft tumors which
      overexpress procaspase-3, and induced no substantial weight loss or
      neurotoxicity. WF-210 and PAC-1 had no effect on the growth of MCF-7 xenograft
      tumors, which do not express procaspase-3. CONCLUSION: We identified WF-210 as a
      potent small-molecule activator of procaspase-3. The favorable antitumor activity
      and acceptable toxicity profile of WF-210 provide a strong rationale for its
      clinical evaluation in the treatment of tumors with high procaspase-3 expression.

PMID- 25053519
TI  - Proteomic and biochemical basis for enhanced growth yield of Enterobacter sp.
      LCR1 on insoluble phosphate medium.
AB  - Proteomics and biochemical analyses were used to unravel the basis for higher
      growth yield of Enterobacter sp. LCR1 on insoluble phosphate medium compared to
      soluble. Proteomic analysis using 2-DE, MALDI-TOF/MS and LC-MS revealed the
      involvement of nine proteins. Down-regulation of fructose bisphosphate aldolase
      with decreased concentrations of glucose-6-phosphate and fructose-6-phosphate
      indicated diminished glycolysis. However, up-regulation of phosphoglycerate
      mutase, increase in the activities of 6-phosphogluconate dehydratase, 2-keto-3
      deoxy-6-phosphogluconate aldolase and 6-phosphogluconate dehydrogenase suggested
      induction of Entner-Doudoroff and pentose phosphate pathways. These pathways
      generate sufficient energy from gluconic acid, which is also used for
      biosynthesis as indicated by up-regulation of elongation factor Tu, elongation
      factor G and protein disulfide isomerase. Increased reactive oxygen species (ROS)
      formation resulting from organic acid oxidation leads to overexpressed manganese
      superoxide dismutase and increased activities of catalase and ascorbate
      peroxidase. Thus the organism uses gluconate instead of glucose for energy, while
      alleviating extra ROS formation by oxidative defense enzymes. 

PMID- 25053520
TI  - Treatment efficacy for pain complaints in women with endometriosis of the lesser
      pelvis after laparoscopic electroablation vs. CO2 laser ablation.
AB  - Endometriosis is a chronic disease affecting mainly women of the reproductive
      age. Its most common manifestations include impaired fecundity, pelvic pain, and
      dyschezia. Laparoscopic removal of endometriotic foci remains to be the gold
      standard for the treatment of endometriosis. More effective techniques of
      endoscopic approach-among others, laser application-are continually being
      developed. The aim of the study was to evaluate the efficacy of laparoscopic
      treatment with the use of CO2 laser ablation vs. electroablation with regard to
      pain complaints in the affected patients. The study included 48 women (aged 22
      42) with varying degrees of endometriosis of the lesser pelvis. The Numeric
      Rating Scale (NRS) was used to evaluate pain intensity before the surgery in all
      patients, followed by either laser ablation or electroablation of the
      endometriotic foci. The results of the laparoscopic treatment were monitored
      after 3 and 6 months postoperatively. p value of 0.05 was considered to be
      statistically significant. Patients from both groups reported less intensive pain
      before/during menstruation (dysmenorrhea) 6 months postoperatively, with more
      distinct tendency in the electroablation group (p = 0.004) as compared to the
      laser ablation group (p = 0.025). Despite the initial improvement reported at the
      3-month checkup (p = 0.008), 6 months postoperatively, a statistically
      significant increase in pain intensity was noted in both groups (p = 0.016 and p
      = 0.032 for CO2 laser ablation and electroablation, respectively). Both surgical
      methods seem to be effective only in the treatment of endometriosis-related
      dysmenorrhea, whereas the intensity of other pain complaints (dyspareunia,
      dysuria, dyschezia, pelvic pain syndrome (PPS)) has remained on the same level.

PMID- 25053521
TI  - Patients' experiences following breast cancer treatment: an exploratory survey of
      personal and work experiences of breast cancer patients from three European
      countries.
AB  - Improved treatments for early breast cancer have led to a significant increase in
      overall survival. While evidence regarding potential long-term sequelae of
      adjuvant treatments exists, relatively little research reports patients' own
      perceptions of change before and after adjuvant chemotherapy (AC). This study
      aimed to identify key ongoing issues associated with AC in daily life. An online
      survey developed for this study was completed by 198 women (mean age 49.7 years)
      in the UK, France and Germany who had AC 1-5 years previously for oestrogen
      receptor positive, HER2 negative early breast cancer. Women without AC and
      endocrine therapy, those treated with Trastuzumab or who had recurrent disease
      were excluded. A third of women who responded were currently unable to perform
      their former family role. The majority had needed support, particularly with
      child care, during treatment. While 54% were in full-time employment before
      diagnosis this had reduced to 32% following AC. Of those women still working,
      over half reported difficulties with tiredness or concentration. Most (85.8%)
      were satisfied with healthcare professionals' treatment information, but only
      29.7% received information about returning to work. This exploratory survey
      highlights areas of women's lives affected 1-5 years following AC for early
      breast cancer. The impact on returning to work and issues surrounding childcare
      particularly, require further study. 

PMID- 25053522
TI  - Seminal vesicle hypoplasia with contralateral renal agenesis.
AB  - Renal agenesis is a rare condition of unknown etiology frequently seen together
      with ipsilateral seminal vesicle and vas deferens anomalies because of common
      embryologic development. However, no cases of contralateral seminal vesicle
      hypoplasia accompanying renal agenesis have previously been reported. We describe
      a case of contralateral seminal vesicle hypoplasia accompanying renal agenesis
      incidentally detected in a 27-year-old presenting to the urology clinic with
      pelvic pain. 

PMID- 25053523
TI  - Juvenile granulosa cell tumor of the testis: a bilateral and synchronous case.
      Should testis-sparing surgery be mandatory?
AB  - Granulosa cell tumor of the testis is an infrequent stromal cell tumor that can
      be distinguished into adult and juvenile, the latter being more common. Juvenile
      granulosa cell tumor of the testis is a rare pathologic finding, accounting for
      1.2%-3.9% of prepubertal testicular tumors. It is considered as a benign stromal
      sex cord tumor and is usually unilateral. Although radical surgery was previously
      considered the treatment of choice, testis-sparing surgery is now recommended in
      all cases where applicable. We report a bilateral synchronous juvenile granulosa
      cell tumor in a 6-month-old child treated with testis-sparing surgery and provide
      a review of the literature. 

PMID- 25053524
TI  - Self-assembled nanostructures of long-acting GnRH analogs modified at position 7.
AB  - It is well known that GnRH analogs can self-assemble into amyloid fibrils and
      that the duration of action of GnRH analogs depends on the ability of the amyloid
      to slowly release active peptides. The aim of this study was to investigate the
      influence of the amino acid residues at position 7 of GnRH analogues on peptide
      self-assembly. It was found that the dominant shape of the nanostructure can be
      changed when the structures of the residues at position 7 differ significantly
      from that of leucine in Degarelix. When the backbone length was extended (peptide
      9), or the side chain of the residue at position 7 was replaced by an aromatic
      ring (peptide 6), or the rotation of the amide bond was restricted (peptide 8),
      the nanostructure changed from fibrils to vesicles. The results also indicate
      that the increasing hydrophilicity had little influence on the nanostructure
      morphology. In addition, a suitable release rate was found to play a more
      important role for the duration of the peptide action by maintaining the
      equilibrium between the drug concentration and the persistent release time, while
      the nanostructure shape was found to exert little influence on the duration of
      the peptide action.

PMID- 25053526
TI  - Ceftriaxone mediated rescue of nigral oxidative damage and motor deficits in MPTP
      model of Parkinson's disease in rats.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by the loss of
      dopamine neurons in the substantia nigra pars compacta along with decreased
      striatal dopamine levels, and consequent extra pyramidal motor dysfunctions
      occur. It has been reported that Ceftriaxone, a beta-lactam antibiotic recently
      had shown to have neuroprotective effects in various neurodegenerative disorder.
      Therefore the present study was designed to investigate the effects of
      Ceftriaxone (CFX) in a MPTP model of Parkinson in rats. MPTP was administered
      intranigrally for the induction of PD in Male Wistar rats. Ceftriaxone (100 and
      200mg/kg) and Ropinirole (1.5 and 3mg/kg) were given intraperitonially, after
      induction of Parkinson's disease for 14 days. Different behavioral performance
      was carried on 1st, 14th, 21st, 28th consecutive days and biochemical parameters
      were estimated on 28th day. Central administration of MPTP showed significant
      impairment of motor behavior and marked increase of oxidative damage and neuro
      inflammmation in rats. However, post treatment with Ceftriaxone (100 and
      200mg/kg) significantly improved the motor deficits and attenuated the oxidative
      damage indicating decreased rise of LPO and nitrite concentration and restored
      the decreased activities of endogenous antioxidant enzyme (Glutathione, Catalase,
      SOD). In addition Ceftriaxone also attenuates the pro-inflammatory cytokines like
      TNF-alpha and IL-beta in striatum region of MPTP induced PD in rats. Ropinirole
      (1.5mg/kg) pretreatment with sub-effective dose of a Ceftriaxone (100mg/kg) had
      significantly enhanced the protective effect of Ceftriaxone as compare to its
      effect with per se group. These results suggested that Ceftriaxone exhibit
      Neuroprotective effect by mediating brain antioxidant defense mechanism and by up
      regulating of dopaminergic pathway and down regulation of glutamatergic pathway. 

PMID- 25053525
TI  - Alterations of the Ca2+ signaling pathway in pancreatic beta-cells isolated from
      db/db mice.
AB  - Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca(2+)
      dependent manner. In diabetic animal models, different aspects of the calcium
      signaling pathway in beta-cells are altered, but there is no consensus regarding
      their relative contributions to the development of beta-cell dysfunction. In this
      study, we compared the increase in cytosolic Ca(2+) ([Ca(2+)]i) via Ca(2+)
      influx, Ca(2+) mobilization from endoplasmic reticulum (ER) calcium stores, and
      the removal of Ca(2+) via multiple mechanisms in beta-cells from both diabetic
      db/db mice and non-diabetic C57BL/6J mice. We refined our previous quantitative
      model to describe the slow [Ca(2+)]i recovery after depolarization in beta-cells
      from db/db mice. According to the model, the activity levels of the two subtypes
      of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump, SERCA2 and SERCA3,
      were severely down-regulated in diabetic cells to 65% and 0% of the levels in
      normal cells. This down-regulation may lead to a reduction in the Ca(2+)
      concentration in the ER, a compensatory up-regulation of the plasma membrane
      Na(+)/Ca(2+) exchanger (NCX) and a reduction in depolarization-evoked Ca(2+)
      influx. As a result, the patterns of glucose-stimulated calcium oscillations were
      significantly different in db/db diabetic beta-cells compared with normal cells.
      Overall, quantifying the changes in the calcium signaling pathway in db/db
      diabetic beta-cells will aid in the development of a disease model that could
      provide insight into the adaptive transformations of beta-cell function during
      diabetes development. 

PMID- 25053527
TI  - Preliminary report on a new hybrid metal stent for EUS-guided biliary drainage
      (with videos).
AB  - BACKGROUND: EUS-guided biliary drainage (EUS-BD) may be a feasible and useful
      alternative in patients with malignant biliary obstruction after failed ERCP. One
      of the main limitations of EUS-BD is the lack of devices specifically tailored to
      this technique. OBJECTIVE: To evaluate a newly developed hybrid metal stent
      customized for EUS-BD. DESIGN: A prospective, observational study. SETTING: A
      tertiary academic referral center. PATIENTS: A total of 27 consecutive patients
      with malignant biliary obstruction who were candidates for alternative techniques
      for biliary drainage because of failed ERCP were enrolled. INTERVENTIONS: EUS-BD
      with a newly developed hybrid metal stent. MAIN OUTCOME MEASUREMENTS: The
      technical and clinical success rates and adverse events, including proximal or
      distal stent migration and cholangitis. RESULTS: EUS-guided hepaticogastrostomy
      was performed in 10 patients, and EUS-guided choledochoduodenostomy was performed
      in 17 patients. The technical success rate of EUS-BD with the hybrid metal stent
      was 100% (27/27), and clinical success was achieved in 96.3% (26/27) of the
      cases. Adverse events developed in 5 patients (5/27, 18.5%), including a self
      limited pneumoperitoneum in 3 patients, minor bleeding in 1 patient, and
      abdominal pain in 1 patient. During the follow-up period (median 134 days),
      proximal or distal stent migration was not observed. LIMITATIONS: This study was
      performed at a single center by a single experienced operator with a relatively
      small number of patients. CONCLUSION: EUS-BD with a hybrid metal stent is
      technically feasible and can be an effective treatment for malignant biliary
      obstruction after failed ERCP. Hybrid metal stents may be used safely in EUS-BD,
      and they can prevent stent-related adverse events.

PMID- 25053528
TI  - The impact of hyoscine-N-butylbromide on adenoma detection during colonoscopy:
      meta-analysis of randomized, controlled studies.
AB  - BACKGROUND: Hyoscine-N-butylbromide (HBB) can induce flattening of colon folds
      through inhibition of smooth muscle activity, which improves mucosal
      visualization. Whether this affects polyp detection is controversial. OBJECTIVE:
      To evaluate whether HBB, administered during colonoscopy, improves polyp and
      adenoma detection. DESIGN: We performed a comprehensive search in MEDLINE and
      EMBASE databases to identify randomized, placebo-controlled trials (RCTs) in
      which HBB was administered during colonoscopy and which also reported the
      detection rate for polyps and/or adenomas (PDR and/or ADR, respectively).
      SETTING: Meta-analysis of 5 RCTs. PATIENTS: A total of 1998 patients (1006
      receiving HBB) were included in the study. INTERVENTIONS: Intravenous
      administration of 20 mg (2 mL) HBB or 2 mL saline solution at the time of cecal
      intubation. MAIN OUTCOME MEASUREMENTS: The PDR was the primary outcome variable.
      Secondary outcomes included the ADR, the advanced adenoma detection rate (adv
      ADR), and the mean number of polyps and adenomas per patient (PPP and APP,
      respectively). RESULTS: The PDR, ADR, and adv-ADR did not differ significantly
      between the 2 groups. The odds ratios (95% confidence interval [CI]) for PDR,
      ADR, and adv-ADR were 1.09, 95% CI, 0.91-1.31; 1.13, 95% CI, 0.92-1.38; and 0.9,
      95% CI, 0.63-1.30, respectively. In addition, no significant differences were
      observed in PPP and APP between the 2 groups. LIMITATIONS: Small number of
      studies included. Limited data about secondary outcomes and safety. CONCLUSION:
      Our meta-analysis does not provide evidence that routine HBB administration at
      cecal intubation improves PDR or ADR. More studies are needed for final
      conclusions, particularly on HBB's effect on PPP and APP.

PMID- 25053529
TI  - Optimal bowel cleansing for colonoscopy: split the dose! A series of meta
      analyses of controlled studies.
AB  - BACKGROUND: Colonoscopy is considered the criterion standard for detecting
      colorectal cancer; adequate preparation is crucial for an effective colonoscopy,
      but definitive data on the optimal preparation are lacking. OBJECTIVE: Our aim
      was to assess the efficacy of split-dose versus non-split-dose preparations, the
      rate of adequate preparation according to type and dose of laxatives, the role of
      "runway time" (the interval time between the last drink of purgative and the
      beginning of colonoscopy), and to evaluate compliance as an additive risk factor
      for colon cleansing. DESIGN: A series of meta-analyses of controlled studies.
      SETTING: Randomized clinical trial of split dose regimen versus entire dose taken
      on the day preceding colonoscopy. PATIENTS: Published trials (1960-2013)
      comparing split-dose versus non-split-dose preparations in adults undergoing
      colonoscopy were selected by using MEDLINE, the Cochrane Central Register of
      Controlled Trials, clinicaltrial.gov, ISI Web of Science, and Scopus.
      INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Rate difference of the
      degree of colon cleansing between split dose and whole dose was the primary
      measure of treatment effect. RESULTS: We included 29 studies. Overall, an
      adequate preparation was obtained in 85% of patients in the split-dose group and
      in 63% of the non-split-dose group (rate difference 22%). The heterogeneity was
      caused by 5 factors: the runway time (the longer, the worse the cleansing), type
      of diet, male sex, use of polyethylene glycol 4 L, and the Jadad score.
      Compliance was significantly higher in the split-dose group. LIMITATIONS: Average
      quality of the included studies and publication bias. CONCLUSION: We provided
      further evidence of the superiority of a split-dose regimen over a non-split-dose
      regimen and showed that, regardless of type and dose, the superiority of split
      dose regimens remains valid if the "golden 5 hours" rule is preserved.

PMID- 25053530
TI  - Expanding the scope and relevance of health interventions: moving beyond clinical
      trials and behavior change models.
AB  - An overemphasis on clinical trials and behavior change models has narrowed the
      knowledge base that can be used to design interventions. The overarching point is
      that the process of overanalyzing variables is impeding the process of gaining
      insight into the everyday experiences that shape how people define health and
      seek treatment. This claim is especially important to health decision-making and
      behavior change because subtle interpretations often influence the decisions that
      people make. This manuscript provides a critique of traditional approaches to
      developing health interventions, and theoretically justifies what and why changes
      are warranted. The limited scope of these models is also discussed, and an
      argument is made to adopt a strategy that includes the perceptions of people as
      necessary for understanding health and health-related decision-making. Three
      practical strategies are suggested to be used with the more standard approaches
      to assessing the effectiveness and relevance of health interventions. 

PMID- 25053532
TI  - Fibroblast growth factor receptors: multifactorial-contributors to tumor
      initiation and progression.
AB  - Fibroblast growth factor receptors (FGFRs), encoded by four genes (FGFR1, FGFR2,
      FGFR3, and FGFR4) are tightly associated with many biological processes such as
      organ development, cell proliferation and migration. Studies over the past
      decades have validated the pivotal roles FGFRs play in tumorigenesis due to the
      regulation of diverse tumorigenesis-related processes, including cell survival,
      proliferation, inflammation, metastasis and angiogenesis. Interestingly, FGFR
      mutations in somatic cells leading to tumorigenesis and those in germ cells
      leading to developmental disorders are identical, suggesting that FGFR mutations
      result in different diseases due to their spatio-temporal expression. Thus,
      discoveries in developmental biology may also be applicable to cancer. FGFRs
      regulate the expression and/or the activity of a myriad of molecules (e.g. matrix
      metalloproteinases (MMPs) and Snail) that are tightly linked to tumorigenesis by
      four main signaling pathways (RAS-MAPK, PI3K-AKT, PLCgamma-PIP2, and STAT), as
      well as other minor branches. Epigenetic and genetic alteration of FGFR genes,
      including DNA methylation, histone remodeling, microRNA regulation, single
      nucleotide polymorphisms (SNPs), gene missense mutations, amplification, and
      fusion of FGFRs with other genes, which result in gain or loss of FGFR function,
      have been identified in many types of cancer. In this review, we focus in
      particular on recent advances in the relationship between FGFR disorders and
      tumorigenesis.

PMID- 25053533
TI  - Cell-cell interactions mediate cytoskeleton organization and collective
      endothelial cell chemotaxis.
AB  - This study investigates the role of cell-cell and cell-ligand interactions in
      cytoskeleton organization of endothelial cells (ECs) and their directional
      migration within a microfluidic device. The migration of ECs in response to a
      biochemical factor was studied. Mathematical analysis of the cell migration
      pathways and cellular cytoskeleton revealed that directional migration, migration
      persistence length, migration speed, and cytoskeletal stress fiber alignment can
      be mediated by the level of cell contacts as well as the presence or absence of a
      biochemical polarizing factor. It was shown that in the presence of a biochemical
      polarizing factor, higher cell density and more frequent cell contacts has a
      reinforcing effect on collective cell chemotaxis. In contrast, in the absence of
      a polarizing factor, high cell density can decrease or suppress the ability of
      the cells to migrate. Also, the correlation of actin stress fiber organization
      and alignment with directional migration of ECs was investigated. It was shown
      that in the presence of a biochemical polarizing factor, stress fibers within the
      cytoskeleton of ECs can be significantly aligned parallel to the gradient
      direction when the cells have higher level of contacts. The results also show
      that the organization and alignment of actin stress fibers is mediated by cell
      adhesion junctions during collective cell migration and introduce cell-cell
      interactions as a key factor during collective cell chemotaxis.

PMID- 25053534
TI  - Multiple overlapping uncovered stents as an alternative flow-diverting strategy
      in the management of peripheral and visceral aneurysms.
AB  - OBJECTIVE: In this study we aimed to report on the midterm outcome of multiple
      overlapping uncovered stents in the treatment of peripheral and visceral
      aneurysms, and analyze the possible factors affecting the treatment efficacy.
      METHODS: Data of patients who were regularly followed up over 24 months were
      retrospectively reviewed. Descriptive statistics were applied to present aneurysm
      thrombosis process and diameter change at each follow-up point, and a comparison
      with the baseline level was performed. Patients were divided into a totally
      thrombosed (TT) group and a residual perfusion (RP) group according to the sac
      thrombosis ratio (thrombus volume to sac volume ratio) at 3, 6, and 12 months of
      follow-up. Aneurysm shrinkage in the two groups was compared to explore the
      effect of the initial RP on the treatment outcome. Patients were also grouped
      based on their aneurysm morphology (saccular/fusiform). The aneurysm sac
      thrombosis speed (time to thrombosis) and diameter decrease (DD) ratio
      (percentage of DD) were compared between the two groups to understand the
      influence of aneurysm shape on the treatment efficacy. RESULTS: Of the 64
      patients treated, the initial 37 patients (25 male; average age, 55.5 +/- 13.0
      years) were enrolled into this study. Technical success rate was 100%. All
      patients were regularly followed up. At 24 months, 94.6% aneurysms (35/37) were
      TT, and the maximum aneurysm diameter decreased from 36.5 +/- 9.7 mm
      preoperatively to 23.6 +/- 7.7 mm (P < .001). Overall clinical success rate
      (complete thrombosis and shrinkage/stabilization of the aneurysm without aneurysm
      related mortality) reached 94.6% in the study cohort. Most side branches (31/33)
      covered by the bare stent stayed patent during follow-up. Initial sac RP at 3, 6,
      and 12 months might not fully affect the final aneurysm DD ratio (TT group: 0.37
      +/- 0.09, 0.35 +/- 0.09, and 0.35 +/- 0.09; compared with the RP group: 0.33 +/-
      0.09, 0.36 +/- 0.11, and 0.36 +/- 0.13; P = .153, .964, and .418, respectively).
      At 3 and 6 months follow-up, saccular aneurysms (n = 29) seemed to have a faster
      thrombosis speed compared with fusiform aneurysms (78.1 +/- 26.8% and 83.9 +/-
      21.8% vs 47.0 +/- 24.4% and 63.9 +/- 22.6%; P = .004 and .013, respectively), but
      there was no significant difference in aneurysm shrinkage ratio at 24 months
      between the two groups (0.36 +/- 0.10 vs 0.33 +/- 0.06; P = .357). CONCLUSIONS:
      Multiple overlapping uncovered stents could be a feasible option for the
      endovascular treatment of peripheral and visceral aneurysms. Neither the aneurysm
      shape nor the initial sac RP would affect the midterm treatment outcome. Further
      validation of this technique is required to substantiate these results.

PMID- 25053535
TI  - Safety and effectiveness of the INCRAFT AAA Stent Graft for endovascular repair
      of abdominal aortic aneurysms.
AB  - OBJECTIVE: This study evaluated the 2-year safety and effectiveness of the
      European First-in-Human INNOVATION trial for the INCRAFT AAA Stent Graft system
      (Cordis Corp, Bridgewater, NJ), an ultra-low-profile device for the treatment of
      abdominal aortic aneurysms. METHODS: From March 2010 to June 2011, the INNOVATION
      prospective multicenter trial involving six centers in Europe enrolled and
      treated 60 asymptomatic patients (95% male; mean age, 74.4 +/- 6.9 years) with
      the INCRAFT System. Main inclusion criteria included proximal aortic neck length
      of 15 mm or more with a diameter up to 27 mm; distal iliac landing zones with a
      length greater than 10 mm and a diameter between 9 and 18 mm; and aortic
      bifurcation >18 mm in diameter and access vessels large enough to accept the 14F
      outer diameter of the delivery system. The primary end point was technical
      success at 1 month; 2-year safety end points included the absence of device- or
      procedure-related major adverse events, absence of type I or III endoleaks, and
      maintenance of device integrity through 2 years of follow-up. Study oversight was
      provided by a Data Safety Monitoring Board with event adjudication by a Clinical
      Events Committee and imaging analysis by an independent core laboratory. RESULTS:
      Of 60 successfully treated patients, two did not come back for their 1-month
      evaluation but remained enrolled in the study; 56 were evaluated at 1 year and 52
      at 2 years. Of the 58 patients, 56 met the 1-month primary safety and
      effectiveness end point (97%; 95% confidence interval, 88%-100%). All patients
      were free from aneurysm enlargement through 2 years. There were no type I or III
      endoleaks at the 2-year time point. All-cause mortality at 2 years was 11.5%, and
      no death was device or procedure related. In total, three patients required a
      postprocedure intervention, two to repair a type I endoleak and one for limb
      occlusion. Core laboratory evaluation of the postoperative imaging studies
      documented absence of endograft migration and stent fractures in all patients.
      CONCLUSIONS: The INCRAFT AAA Stent Graft System provides a durable solution for
      patients with abdominal aortic aneurysms, with a low frequency of device-related
      events through 2 years of follow-up.

PMID- 25053536
TI  - Efficient purification of CD4+ lymphocytes from peripheral blood progenitor cell
      products using affinity bead acoustophoresis.
AB  - Processing of peripheral blood progenitor cells (PBPC) for clinical
      transplantation or research applications aims to effectively isolate or deplete
      specific cell populations, utilizing primarily magnetic or fluorescence activated
      sorting methods. Here, we investigated the performance of microfluidic
      acoustophoresis for the separation of lymphocyte subsets from PBPC, and present a
      novel method for affinity-bead-mediated acoustic separation of cells which can
      otherwise not be acoustically discriminated. As the acoustic force on a particle
      depends on particle size, density and compressibility, targeting of cells by
      affinity specific beads will generate cell-bead complexes that exhibit distinct
      acoustic properties relative to nontargeted cells and are, thus, possible to
      isolate. To demonstrate this, PBPC samples (n = 22) were obtained from patients
      and healthy donors. Following density gradient centrifugation, cells were labeled
      with anti-CD4-coated magnetic beads (Dynal) and isolated by acoustophoresis and,
      for comparison, standard magnetic cell sorting technique in parallel. Targeted
      CD4+ lymphocytes were acoustically isolated with a mean (+/-SD) purity of 87 +/-
      12%, compared with 96 +/- 3% for control magnetic sorting. Viability of sorted
      cells was 95 +/- 4% (acoustic) and 97 +/- 3% (magnetic), respectively. The mean
      acoustic separation efficiency of CD4+ lymphocytes to the target fraction was 65
      +/- 22%, compared with a mean CD4+ lymphocyte recovery of 56 +/- 15% for magnetic
      sorting. Functional testing of targeted CD4+ lymphocytes demonstrated unimpaired
      mitogen-mediated proliferation capacity and cytokine production. Hematopoietic
      progenitor cell assays revealed a preserved colony forming ability of nontarget
      cells post sorting. We conclude that the acoustophoresis platform can be utilized
      to efficiently isolate bead-labeled CD4+ lymphocytes from PBPC samples in a
      continuous flow format, with preserved functional capacity of both target and
      nontarget cells. These results open up for simultaneous affinity-bead-mediated
      separation of multiple cell populations, something which is not possible with
      current standard magnetic cell separation technology. (c) 2014 International
      Society for Advancement of Cytometry. 

PMID- 25053539
TI  - Abstracts of the 25th Annual Scientific Meeting of the Stroke Society of
      Australasia, 30 July-1 August 2014, Hamilton island, Queensland, Australia.

PMID- 25053537
TI  - Mechanotransduction in epidermal Merkel cells.
AB  - The cellular and molecular basis of vertebrate touch reception remains least
      understood among the traditional five senses. Somatosensory afferents that
      innervate the skin encode distinct tactile qualities, such as flutter, slip, and
      pressure. Gentle touch is thought to be transduced by somatosensory afferents
      whose tactile end organs selectively filter mechanical stimuli. These tactile end
      organs comprise afferent terminals in association with non-neuronal cell types
      such as Merkel cells, keratinocytes, and Schwann cells. An open question is
      whether these non-neuronal cells serve primarily as passive mechanical filters or
      whether they actively participate in mechanosensory transduction. This question
      has been most extensively studied in Merkel cells, which are epidermal cells that
      complex with sensory afferents in regions of high tactile acuity such as
      fingertips, whisker follicles, and touch domes. Merkel cell-neurite complexes
      mediate slowly adapting type I (SAI) responses, which encode sustained pressure
      and represent object features with high fidelity. How Merkel cells contribute to
      unique SAI firing patterns has been debated for decades; however, three recent
      studies in rodent models provide some direct answers. First, whole-cell
      recordings demonstrate that Merkel cells are touch-sensitive cells with fast,
      mechanically activated currents that require Piezo2. Second, optogenetics and
      intact recordings show that Merkel cells mediate sustained SAI firing. Finally,
      loss-of-function studies in transgenic mouse models reveal that SAI afferents are
      also touch sensitive. Together, these studies identify molecular mechanisms of
      mechanotransduction in Merkel cells, reveal unexpected functions for these cells
      in touch, and support a revised, two-receptor site model of mechanosensory
      transduction. 

PMID- 25053538
TI  - Mechanosensory molecules and circuits in C. elegans.
AB  - Mechanosensory neurons, whose activity is controlled by mechanical force,
      underlie the senses of touch, hearing, and proprioception, yet despite their
      importance, the molecular basis of mechanotransduction is poorly understood.
      Genetic studies in Caenorhabditis elegans have provided a useful approach for
      identifying potential components of mechanotransduction complexes that might be
      conserved in more complex organisms. This review describes the mechanosensory
      systems of C. elegans, including the sensory neurons and circuitry involved in
      body touch, nose touch, and proprioception. In addition, the roles of genes
      encoding known and potential mechanosensory receptors, including members of the
      broadly conserved transient receptor potential (TRP) and degerin/epithelial Na(+)
      channel (DEG/ENaC) channel families, are discussed. 

PMID- 25053540
TI  - [Controlled clinical trial on renal denervation in resistant hypertension].

PMID- 25053541
TI  - [Acute mesenteric ischemia].

PMID- 25053542
TI  - Second opinion in breast pathology: policy, practice and perception.
AB  - AIMS: To assess the laboratory policies, pathologists' clinical practice and
      perceptions about the value of second opinions for breast pathology cases among
      pathologists practising in the USA. METHODS: Cross-sectional data were collected
      from 252 pathologists who interpret breast specimens in eight states using a web
      based survey. Descriptive statistics were used to characterise findings. RESULTS:
      Most participants had >10 years of experience interpreting breast specimens
      (64%), were not affiliated with academic centres (73%) and were not considered
      experts by their peers (79%). Laboratory policies mandating second opinions
      varied by diagnosis: invasive cancer 65%; ductal carcinoma in situ (DCIS) 56%;
      atypical ductal hyperplasia 36% and other benign cases 33%. 81% obtained second
      opinions in the absence of policies. Participants believed they improve
      diagnostic accuracy (96%) and protect from malpractice suits (83%), and were easy
      to obtain, did not take too much time and did not make them look less adequate.
      The most common (60%) approach to resolving differences between the first and
      second opinion is to ask for a third opinion, followed by reaching a consensus.
      CONCLUSIONS: Laboratory-based second opinion policies vary for breast pathology
      but are most common for invasive cancer and DCIS cases. Pathologists have
      favourable attitudes towards second opinions, adhere to policies and obtain them
      even when policies are absent. Those without a formal policy may benefit from
      supportive clinical practices and systems that help obtain second opinions.

PMID- 25053543
TI  - p-mTOR expression is associated with better prognosis in luminal breast
      carcinoma.
AB  - AIMS: Despite considerable interest in the PI3K/AKT/mTOR pathway in breast
      carcinomas (BC), published data reports contradictory results regarding the
      association of phosphorylated mammalian target of Rapamycin (p-mTOR) expression
      with clinico-pathological features and prognosis in BC. Here, we evaluate the
      main clinico-pathological associations with p-mTOR expression in BC, with focus
      on the different molecular subtypes. METHODS: In this retrospective study, 331 BC
      patients were included in final analysis. Outcome measures included disease-free
      survival (DFS) and overall survival (OS) times. Baseline data and outcome
      measures were compared between immunohistochemical p-mTOR expressing and non
      expressing BCs. Subgroup analysis was performed to assess the effect of p-mTOR
      expression in the outcome for each BC molecular subtype. RESULTS: 43.8% of the
      tumours were positive for p-mTOR, with a significant correlation between p-mTOR
      expression with smaller (<2 cm) (p=0.021) and lower-grade tumours (p<0.001).
      Expression of p-mTOR was also associated with longer DFS (HR of 0.32, p<0.001)
      and OS (HR of 0.20, p<0.001). In a multivariable analysis, the HR remained
      significant with minimal change (HR=0.26, p=0.002 for OS; HR=0.40, p=0.002 for
      DFS). In subgroup analysis, luminal p-mTOR-expressing tumours demonstrated longer
      DFS and OS (HR 0.33, p=0.003; HR 0.20, p=0.003, respectively) independently of
      size, grade, lymph node status and Her-2 overexpression. CONCLUSIONS: p-mTOR
      expression is associated with smaller, lower-grade and with luminal BC. In
      multivariable analysis, p-mTOR expression was associated with longer DFS and OS,
      independently of the size, grade and lymph node status, especially in luminal
      BCs.

PMID- 25053544
TI  - Gastric neuroendocrine neoplasms and related precursor lesions.
AB  - Gastric neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours
      showing different clinicopathological features and behaviour, implying a wide
      spectrum of therapeutic options. They are currently classified using the 2010 WHO
      classification of digestive neuroendocrine neoplasms into G1-neuroendocrine
      tumours (NETs), G2-NETs, neuroendocrine carcinomas (NECs) and mixed
      adenoneuroendocrine carcinomas (MANECs). However, most gastric NENs are composed
      of ECL-cells (ECL-cell NETs) that can be preceded by ECL-cell hyperplastic and
      dysplastic lesions, whose oncologic potential has not yet been completely
      elucidated. ECL-cell NETs differ considerably in terms of prognosis depending on
      the proliferative status and clinicopathological background. The integration of
      both aspects in the diagnostic pathway may help to better classify tumours in
      different prognostic categories, especially when diagnosing them in small bioptic
      specimens. NECs are all poorly differentiated, highly aggressive carcinomas,
      while MANECs can show different morphological features that are directly
      associated with different prognoses. Precursor lesions of such carcinomas are not
      entirely understood. In this review, the clinicopathological features of gastric
      NENs and related precursor lesions will be described to give the reader a
      comprehensive overview on this topic. 

PMID- 25053545
TI  - Roles of Chinese medicine bioactive ingredients in the regulation of cellular
      function of endothelial progenitor cells.
AB  - To improve the function of endothelial progenitor cells (EPCs) is one of the
      goals in Chinese traditional therapy to treat various cardio-celebrovascular
      diseases. In the past decades, scholars in the field of traditional Chinese
      medicine (TCM) have found fifteen active compounds to regulate the function of
      EPC. These metabolites are extracted from thirteen, plant-based Chinese medicine,
      with majority of them as potent reductive or oxidative hydrophilic molecules
      containing phenyl groups. These active compounds either enhance the mobilization
      of EPC, or inhibit their apoptosis through different signaling pathways. In this
      review, the molecular structure, biophysical properties, and the plant sources of
      these active ingredients and their regulatory effects on the function of EPC are
      summarized, aiming to reveal the modern basis of Chinese medicine for promoting
      blood circulation and removing blood stasis at the progenitor cell level. 

PMID- 25053546
TI  - Hepatoprotective activity of Gentiana veitchiorum Hemsl. against carbon
      tetrachloride-induced hepatotoxicity in mice.
AB  - AIM: To study the hepatoprotective effect of methanol extract of Gentiana
      veitchiorum (MGV) against CCl4-induced oxidative stress and liver injury in mice.
      METHOD: The acute hepatic model was developed by injection of 20% CCl4 in mice.
      ICR mice were divided into six groups, including control, CCl4, CCl4(+)
      silymarin, and CCl4(+) MGV (100, 200, and 400 mg.kg(-1)) groups. Hepatic enzymes
      including AST, ALT and ALP levels in serum, and antioxidant enzymes, including
      SOD, CAT and GPX activity in liver tissue, were determined. Histopathological
      examination and Western blot analysis were performed. RESULTS: Oral
      administration of MGV at 200 and 400 mg.kg(-1) for 15 days dose-dependently
      inhibited the serum elevations of AST, ALT, and ALP, and recovered the reduction
      of SOD, CAT, and GPX in liver tissue. Hematoxylin and eosin staining examination
      performed in liver tissues suggested that MGV treatment ameliorated
      histopathological changes in CCl4-induced mice. Western blotting analysis implied
      that MGV increased HO-1 expression and recovered TNF-alpha alternation.
      CONCLUSION: G. veitchiorum can protect the liver against CCl4-induced damage in
      mice, and this hepatoprotective effect was due at least in part to its ability
      through scavenging CCl4-associated free radical activities. The study provided in
      vivo evidence that G. veitchiorum can be used as a safe, cheap, and effective
      agent to reduce acute liver damage, supporting its folk medicine use.

PMID- 25053547
TI  - Protective effect of Nigella sativa oil against binge ethanol-induced oxidative
      stress and liver injury in rats.
AB  - AIM: Nigella sativa L. (Ranunculaceae) is considered as a therapeutic plant-based
      medicine for liver damage. In this study, the aim was to study the effect of
      Nigella sativa oil (NSO) pretreatment on ethanol-induced hepatotoxicity in rats.
      METHOD: Rats were given Nigella sativa oil at doses of 2.5 and 5.0 mL.kg(-1),
      orally for 3 weeks, followed by oral ethanol (EtOH) administration (5 g.kg(-1))
      every 12 h three times (binge model). RESULTS: Binge ethanol application caused
      significant increases in plasma transaminase activities and hepatic triglyceride
      and malondialdehyde (MDA) levels. It decreased hepatic glutathione (GSH) levels,
      but did not change vitamins E and vitamin C levels and antioxidant enzyme
      activities. NSO (5.0 mL.kg(-1)) pretreatment significantly decreased plasma
      transaminase activities, hepatic MDA, and triglyceride levels together with
      amelioration in hepatic histopathological findings. CONCLUSION: NSO pretreatment
      may be effective in protecting oxidative stress-induced hepatotoxicity after
      ethanol administration.

PMID- 25053548
TI  - Anti-asthma effects of synthetic salidroside through regulation of Th1/Th2
      balance.
AB  - AIM: The aim of the study was to investigate the effect and mechanism of action
      of synthetic salidroside in an ovalbumin (OVA)-induced asthma model in mice.
      METHOD: BALB/c mice were sensitized with an intraperitoneal injection of
      ovalbumin (OVA) to induce a mouse model of asthma in paracmasis. The mice were
      treated with dexamethasone as the positive control. At the end of the study,
      respiratory reactivity was detected, the numbers of various kinds of white blood
      cells in the bronchoalveolar lavage fluid (BALF) were counted, and the levels of
      IL-4 and INF-gamma in BALF were determined. Quantitative PCR was used to detect
      the mRNA contents of IL-4 and INF-gamma in lung tissue. Histologic examination
      was performed to observe inflammatory cellular infiltration. RESULTS: Salidroside
      treatment virtually eliminated airway hyper-reactivity, markedly reduced the
      eosinophil percent, obviously reduced the levels of IL-4 and raised INF-gamma in
      the bronchoalveolar lavage fluid (BALF) compared with the sham-treated group.
      Quantitative PCR on the mRNA content of IL-4 and INF-gamma provided confirmation.
      Lung histologic observations showed that salidroside reduced inflammation and
      edema. These effects were equivalent to the effects of dexamethasone. CONCLUSION:
      Synthetic salidroside exhibits an anti-asthma effect which is related to the
      regulation of Th1/Th2 balance. This provides a new possibility for treatment of
      allergic asthma.

PMID- 25053549
TI  - Antioxidant activity of Ziziphora tenuoir methanolic extracts and comparison of
      the essential oil in two stages of growth.
AB  - Flavonoids, anthocyanins, antioxidant capability, total phenolic, ascorbic acid
      contents, and essential oils compounds of Ziziphora tenuoir (Lamiaceae) for polar
      and non-polar subfraction in different stages of growth (pre-flowering and
      flowering) were evaluated in this work. Antioxidant activities of the samples
      were determined by three testing systems namely DPPH, beta-carotene/linoleic
      acid, and reducing power assay. In the DPPH system, the highest radical
      scavenging activity was seen by the nonpolar subfraction of the methanol extract
      in the flowering stage (IC50 43.17 +/- 3.68 MUg.mL(-1)). Large differences in the
      amount of phenolic compounds, antioxidant activity, anthocyanins, and flavonoids
      of Z. tenuoir in two stages of growth were detected. The chemical composition of
      the hydrodistilled essential oil of the aerial parts of Z. tenuoir was analyzed
      by GC/MS and compared in the two stages of growth. The main constituents of the
      28 identified compounds in the oil were found to be pulegone (67.34% vs 59.61%),
      beta-humulene (3.24% vs 3.25%), and limonene (5.06% vs 2.57%) at the flowering
      and pre-flowering stages, respectively. 

PMID- 25053550
TI  - A new cytochalasin from endophytic Phomopsis sp. IFB-E060.
AB  - AIM: To study the chemical constituents of the solid culture of the endophyte
      Phomopsis sp. IFB-E060 in Vatica mangachapoi. METHOD: Isolation and purification
      were performed through silica gel column chromatography, gel filtration over
      Sephadex LH-20, ODS column chromatography, and HPLC. Structures of the isolated
      compounds were elucidated by a combination of spectroscopic analyses (UV, CD, IR,
      MS, 1D, and 2D NMR). The cytotoxicity of the isolates was evaluated in vitro by
      the MTT method against the human hepatocarcinoma cell line SMMC-7721. RESULTS:
      Five compounds were isolated from the solid culture of the endophyte Phomopsis
      sp. IFB-E060 and their structures were identified as 18-methoxy cytochalasin J
      (1), cytochalasin H (2), (22E, 24S)-cerevisterol (3), ergosterol (4), and
      nicotinic acid (5). Compound 1 had an inhibition rate of 24.4% at 10 MUg.mL(-1)
      and 2 had an IC50 value of 15.0 MUg.mL(-1), while a positive control 5
      fluorouracil had an inhibition rate of 28.7% at 10 MUg.mL(-1). CONCLUSION: 18
      Methoxy cytochalasin J (1), produced by endophytic Phomopsis sp. IFB-E060, is a
      new cytochalasin with weak cytotoxicity to the human hepatocarcinoma cell line
      SMMC-7721.

PMID- 25053551
TI  - The integrated quality assessment of Chinese commercial dry red wine based on a
      method of online HPLC-DAD-CL combined with HPLC-ESI-MS.
AB  - AIM: To apply an integrated quality assessment strategy to investigate the
      quality of multiple Chinese commercial dry red wine samples. METHOD: A
      comprehensive method was developed by combining a high performance liquid
      chromatography-diode array detector-chemiluminescence (HPLC-DAD-CL) online
      hyphenated system with an HPLC-ESI-MS technique. RESULTS: Chromatographic and
      H2O2-scavenging active fingerprints of thirteen batches of different,
      commercially available Chinese dry red wine samples were obtained and analyzed.
      Twenty-five compounds, including eighteen antioxidants were identified and
      evaluated. The dominant and characteristic antioxidants in the samples were
      identified. The relationships between antioxidant potency and the cultivated
      variety of grape, producing area, cellaring period, and trade mark are also
      discussed. CONCLUSION: The results provide the feasibility for an integrated
      quality assessment strategy to be efficiently and objectively used in quality
      (especially antioxidant activity) assessment and identification of dry red wine.

PMID- 25053552
TI  - Fingerprint analysis of Zhimu-Huangbai herb pair and simultaneous determination
      of its alkaloids, xanthone glycosides and steroidal saponins by HPLC-DAD-ELSD.
AB  - AIM: To develop and validate a high performance liquid chromatography (HPLC)
      coupled with diode array and evaporative light scattering detectors (DAD-ELSD)
      method for the quantitative determination and fingerprint analysis of ten active
      constituents in three chemical classes (namely, xanthone glycosides, steroidal
      saponins, and alkaloids) in Zhimu-Huangbai herb pair (ZB). METHOD:
      Chromatographic separation was performed on a Diamonsil C18 column (4.6 mm * 250
      mm, 5 MUm, Dikma) by gradient elution using acetic acid in acetonitrile solution
      at a flow rate of 1.0 mL.min(-1) at 260 nm. The drift tube temperature of ELSD
      was set to 60  degrees C and nebulizer gas pressure was 4.0 Bar. Method
      validation was performed to assure its linearity, limits of detection and
      quantification, precision, repeatability, stability, and accuracy. RESULTS: The
      HPLC-DAD-ELSD method allowed the quantification of ten compounds (phellodendrine,
      jatrorrhizine, palmatine, berberine, neomangiferin, mangiferin, timosaponin E-I,
      timosaponin B-II, timosaponin B, and timosaponin A-III), and was successfully
      applied to fingerprint analysis for ten batches of ZB samples. CONCLUSION: This
      was the first time to apply the combination of DAD and ELSD for the simultaneous
      determination of ten active ingredients in ZB. The results showed that the
      combination of quantitative analysis for marker ingredients and chemical
      fingerprint for the TCM herb pair provides a potentially powerful, widely
      introduced, and internationally accepted strategy for assessment of complex TCM
      formulas.

PMID- 25053553
TI  - Screening and identification of multiple components in Tanreqing injection using
      RP-HPLC combined with DAD and ESI-TOF/MS.
AB  - A liquid chromatography coupled with diode array detector (DAD) and electrospray
      ionization time-of-flight mass spectrometry (ESI-TOF/MS) method was developed for
      the screening and identification of the multiple components in Tanreqing
      injection, a well-known Chinese medicine injection in China. By combining the DAD
      spectrum and the accurate mass measurement of ESI-TOF/MS, twelve components in
      Tanreqing injection were identified. This study contributes to clarifying the
      nature of Tanreqing injection, and provides an effective and reliable process for
      the comprehensive and systematic characterization of complex traditional Chinese
      medicine preparations. 

PMID- 25053554
TI  - Identification and comparative analysis of the major chemical constituents in the
      extracts of single fuzi herb and fuzi-gancao herb-pair by UFLC-IT-TOF/MS.
AB  - AIM: The aim of this work was to establish a specific and sensitive method to
      comprehensively investigate and compare chemical constituents of Fuzi-Gancao herb
      pair (FG), consisting of Aconitum carmichaelii Debeaux (Fuzi, Chinese) and Roast
      Radix Glycyrrhizae (Glycyrrhiza glabra L., Gancao, in Chinese) and Fuzi alone to
      explore the underlying interaction mechanism of FG. METHOD: An ultra-fast liquid
      chromatography-ion trap/time-of-flight mass spectrometry (UFLC/MS-IT-TOF) method
      using diazepam as internal standard was developed for the identification and semi
      quantitative analysis of the phytochemical constituents of Fuzi and FG.
      Chromatographic separation was achieved on a UFLC column using a gradient program
      with 40 mmol.L(-1) ammonium acetate and acetonitrile as the mobile phase.
      RESULTS: Fifty-one of the sixty compounds, including forty-five C19-diterpenoid
      alkaloids and six C20-diterpenoid alkaloids were tentatively identified in the
      extracts of Fuzi and FG through accurate mass measurements and fragmentation
      patterns. Comparing the contents of these alkaloids in these two extracts, it was
      found that the diester-diterpenoid alkaloids (DDAs) and the alkylolamine
      diterpenoid alkaloids (ADAs) were increased, while the monoester-diterpenoid
      alkaloids (MDAs) were decreased in the extracts of FG. CONCLUSION: This work
      provided comprehensive information for the quality control of Fuzi preparations,
      and the further investigation on the compatibility mechanisms of FG.

PMID- 25053555
TI  - Absorption characteristics of the total alkaloids from Mahonia bealei in an in
      situ single-pass intestinal perfusion assay.
AB  - AIM: To investigate the absorption characteristics of the total alkaloids from
      Mahoniae Caulis (TAMC) through the administration of monterpene absorption
      enhancers or protein inhibitors. METHOD: The absorption behavior was investigated
      in an in situ single-pass intestinal perfusion (SPIP) assay in rats. RESULTS: The
      intestinal absorption of TAMC was much more than that of a single compound or a
      mixture of compounds (jatrorrhizine, palmatine, and berberine). Promotion of
      absorption by the bicyclic monoterpenoids (borneol or camphor) was higher than by
      the monocyclic monoterpenes (menthol or menthone), and promotion by compounds
      with a hydroxyl group (borneol or menthol) was higher than those with a carbonyl
      group (camphor or menthone). The apparent permeability coefficient (Papp) of TAMC
      was increased to 1.8-fold by verapamil, while it was reduced to one half by
      thiamine. The absorption rate constant (Ka) and Papp of TAMC were unchanged by
      probenecid and pantoprazole. CONCLUSION: The intestinal absorption
      characteristics of TAMC might be passive transport, and the intestinum tenue was
      the best absorptive site. In addition, TAMC might be likely a substrate of P
      glycoprotein (P-gp) and organic cation transporters (OCT), rather than multidrug
      resistance protein (MRP) and breast cancer resistance protein (BCRP). Compared
      with a single compound and a mixture of compounds, TAMC was able to be absorbed
      in the blood circulation effectively.

PMID- 25053556
TI  - The resolution of inflammation: a mathematical model of neutrophil and macrophage
      interactions.
AB  - There is growing interest in inflammation due to its involvement in many diverse
      medical conditions, including Alzheimer's disease, cancer, arthritis and asthma.
      The traditional view that resolution of inflammation is a passive process is now
      being superceded by an alternative hypothesis whereby its resolution is an
      active, anti-inflammatory process that can be manipulated therapeutically. This
      shift in mindset has stimulated a resurgence of interest in the biological
      mechanisms by which inflammation resolves. The anti-inflammatory processes
      central to the resolution of inflammation revolve around macrophages and are
      closely related to pro-inflammatory processes mediated by neutrophils and their
      ability to damage healthy tissue. We develop a spatially averaged model of
      inflammation centring on its resolution, accounting for populations of
      neutrophils and macrophages and incorporating both pro- and anti-inflammatory
      processes. Our ordinary differential equation model exhibits two outcomes that we
      relate to healthy and unhealthy states. We use bifurcation analysis to
      investigate how variation in the system parameters affects its outcome. We find
      that therapeutic manipulation of the rate of macrophage phagocytosis can aid in
      resolving inflammation but success is critically dependent on the rate of
      neutrophil apoptosis. Indeed our model predicts that an effective treatment
      protocol would take a dual approach, targeting macrophage phagocytosis alongside
      neutrophil apoptosis. 

PMID- 25053557
TI  - Modelling the dynamics of bluetongue disease and the effect of seasonality.
AB  - We present mathematical models for the midge-borne disease bluetongue, with
      cattle and sheep as hosts. The models take the form of delay differential
      equations and incorporate the incubation time of bluetongue in cattle, sheep and
      midges, and also the larval developmental time of midges. Recovery in cattle and
      sheep is also included. Both an autonomous and a periodic model are considered,
      to take account of seasonality. For both models we present conditions for the
      disease-free state to be linearly stable, and a detailed interpretation of those
      conditions. The results of simulations are also presented. Important findings
      include the need for prompt diagnosis of latent infection and appropriate action
      before the animal turns infectious, and the need for measures that reduce insect
      bites. 

PMID- 25053558
TI  - Dietary zinc deficiency effects dorso-lateral and ventral prostate of Wistar
      rats: histological, biochemical and trace element study.
AB  - Zinc deficiency has become a global problem affecting the developed and
      developing countries due to inhibitors in the diet which prevents its absorption
      or due to a very low concentration of bioavailable zinc in the diet. Being
      present in high concentration in the prostate and having diverse biological
      function, we investigated the effects of dietary zinc deficiency for 2 and 4
      weeks on dorso-lateral and ventral prostate. Sixty prepubertal rats were divided
      into three groups: zinc control (ZC), pair fed (PF) and zinc deficient (ZD) and
      fed on 100 MUg/g (zinc control and pair fed groups) and 1 MUg/g (zinc deficient)
      diet. Zinc deficiency was associated with degenerative changes in dorso-lateral
      and ventral prostate as made evident by karyolysis, karyorhexis, cytoplasmolysis,
      loss of cellularisation, decreased intraluminar secretion and degeneration of
      fibromuscular stroma. In response, protein carbonyl, nitric oxide, acid
      phosphatase, 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid
      dehydrogenase increased, exhibiting variable level of significance. Total protein
      and total zinc concentration in dorso-lateral and ventral prostate as well as in
      serum decreased (P < 0.001). Decrease (P < 0.001) was recorded in serum FSH and
      testosterone after 2 and 4 weeks of zinc deficiency. The changes were more
      prominent after 4 weeks of synthetic zinc deficient diet. The results indicate
      that zinc deficiency during prepubertal period affects the prostate structure,
      total protein concentration, enhanced protein carbonyl concentration, nitric
      oxide as well as acid phosphatase activities and impaired hydroxysteroid
      dehydrogenase activities. Evidently these changes could be attributed to
      dysfunction of dorso-lateral and ventral prostate after dietary zinc deficiency
      as well as impairment of metabolic and secretory activity, reduced gonadotropin
      levels by hypothalamus -hypophysial system which is indicative of a critical role
      of zinc in maintaining the prostate integrity.

PMID- 25053560
TI  - Modelling of human herpesvirus infections in humanized mice.
AB  - The human herpesviruses (HHVs) are remarkably successful human pathogens, with
      some members of the family successfully establishing infection in the vast
      majority of humans worldwide. Although many HHV infections result in asymptomatic
      infection or mild disease, there are rare cases of severe disease and death found
      with nearly every HHV. Many of the pathogenic mechanisms of these viruses are
      poorly understood, and in many cases, effective antiviral drugs are lacking. Only
      a single vaccine exists for the HHVs and researchers have been unable to develop
      treatments to cure the persistent infections associated with HHVs. A major
      hindrance to HHV research has been the lack of suitable animal models, with the
      notable exception of the herpes simplex viruses. One promising area for HHV
      research is the use of humanized mouse models, in which human cells or tissues
      are transplanted into immunodeficient mice. Current humanized mouse models mostly
      transplant human haematopoietic stem cells (HSCs), resulting in the production of
      a variety of human immune cells. Although all HHVs are thought to infect human
      immune cells, the beta- and gammaherpesviruses extensively infect and establish
      latency in these cells. Thus, mice humanized with HSCs hold great promise to
      study these herpesviruses. In this review, we provide a historical perspective on
      the use of both older and newer humanized mouse models to study HHV infections.
      The focus is on current developments in using humanized mice to study mechanisms
      of HHV-induced pathogenesis, human immune responses to HHVs and effectiveness of
      antiviral drugs. 

PMID- 25053561
TI  - Single-stranded positive-sense RNA viruses generated in days using infectious
      subgenomic amplicons.
AB  - Reverse genetics is a key methodology for producing genetically modified RNA
      viruses and deciphering cellular and viral biological properties, but methods
      based on the preparation of plasmid-based complete viral genomes are laborious
      and unpredictable. Here, both wild-type and genetically modified infectious RNA
      viruses were generated in days using the newly described ISA (infectious
      subgenomic-amplicons) method. This new versatile and simple procedure may enhance
      our capacity to obtain infectious RNA viruses from PCR-amplified genetic
      material.

PMID- 25053562
TI  - Mutant USA strain of porcine circovirus type 2 (mPCV2) exhibits similar virulence
      to the classical PCV2a and PCV2b strains in caesarean-derived, colostrum-deprived
      pigs.
AB  - In 2012, a mutant porcine circovirus type 2 (mPCV2) strain was identified in
      cases of PCV-associated disease (PCVAD) in the USA. The mPCV2 had an additional
      amino acid, lysine (K), in the capsid at position 234. The objectives of this
      study were to compare the pathogenicity of mPCV2, PCV2a and PCV2b in pigs using
      biologically pure infectious virus stocks derived from respective infectious DNA
      clones, and to investigate the importance of genotype-specific ORF2 and the
      presence of lysine at position 234 of the capsid. A total of 47, 2-week-old,
      caesarean-derived, colostrum-deprived (CDCD) pigs were assigned to one of seven
      groups. At 3 weeks of age, the pigs were experimentally inoculated with saline,
      PCV2a, PCV2b, mPCV2, PCV2b-234-K (lysine addition in ORF2), chimeric PCV2b
      ORF1/mPCV2-ORF2 or reciprocal chimeric mPCV2-ORF1/PCV2b-ORF2. All pigs were
      necropsied 21 days post-infection (p.i.). Gross lesions were limited to visible
      icterus and loss of body condition in a portion of the mPCV2 pigs. The amount of
      PCV2 DNA was significantly higher in pigs inoculated with mPCV2 compared with
      PCV2b in sera at 7 days p.i. and faecal swabs at 14 days p.i. Based on lymphoid
      lesions, a higher prevalence of PCVAD was seen in pigs infected with PCV2s
      containing the additional 234-K (64.3 %) compared with those infected with a PCV2
      with the regular 233 bp ORF2 (40 %). Results indicated that all PCV2 isolates
      were capable of inducing severe lesions and disease in the CDCD pig model, and
      there was no significant difference in virulence.

PMID- 25053563
TI  - Critical role for bone marrow stromal antigen 2 in acute Chikungunya virus
      infection.
AB  - Bone marrow stromal antigen 2 (BST-2; also known as tetherin or CD317) is an IFN
      inducible gene that functions to block the release of a range of nascent
      enveloped virions from infected host cells. However, the role of BST-2 in viral
      pathogenesis remains poorly understood. BST-2 plays a multifaceted role in innate
      immunity, as it hinders retroviral infection and possibly promotes infection with
      some rhabdo- and orthomyxoviruses. This paradoxical role has probably hindered
      exploration of BST-2 antiviral function in vivo. We reported previously that BST
      2 tethers Chikungunya virus (CHIKV)-like particles on the cell plasma membrane.
      To explore the role of BST-2 in CHIKV replication and host protection, we
      utilized CHIKV strain 181/25 to examine early events during CHIKV infection in a
      BST-2(-/-) mouse model. We observed an interesting dichotomy between WT and BST
      2(-/-) mice. BST-2 deficiency increased inoculation site viral load, culminating
      in higher systemic viraemia and increased lymphoid tissues tropism. A suppressed
      inflammatory innate response demonstrated by impaired expression of IFN-alpha,
      IFN-gamma and CD40 ligand was observed in BST-2(-/-) mice compared with the WT
      controls. These findings suggested that, in part, BST-2 protects lymphoid tissues
      from CHIKV infection and regulates CHIKV-induced inflammatory response by the
      host.

PMID- 25053564
TI  - Neuraminidase gene homology contributes to the protective activity of influenza
      vaccines prepared from the influenza virus library.
AB  - Whole-virus (WV) vaccines from influenza A/duck/Hokkaido/77 (H3N2), and its
      reassortant strains H3N4, H3N5 and H3N7, which have the same haemagglutinin (HA)
      gene but different neuraminidase (NA) genes, were prepared from our influenza
      virus library. Mice were intranasally immunized with equivalent doses of each
      vaccine (1-0.01 ug per mouse). All of the mice that received the highest dose of
      each vaccine (1 ug per mouse) showed equivalent high HA-inhibiting (HI) antibody
      titres and survived the H3N2 challenge viruses. However, mice that received lower
      doses of vaccine (0.1 or 0.01 ug per mouse) containing a heterologous NA had
      lower survival rates than those given the H3N2-based vaccine. The lungs of mice
      challenged with H3N2 virus showed a significantly higher virus clearance rate
      when the vaccine contained the homologous NA (N2) versus a heterologous NA,
      suggesting that NA contributed to the protection, especially when the HI antibody
      level was low. These results suggested that, even if vaccines prepared for a
      possible upcoming pandemic do not induce sufficient HI antibodies, WV vaccines
      can still be effective through other matched proteins such as NA.

PMID- 25053565
TI  - Endocannabinoid CB1 antagonists inhibit hepatitis C virus production, providing a
      novel class of antiviral host-targeting agents.
AB  - Direct-acting antivirals have significantly improved treatment outcomes in
      chronic hepatitis C (CHC), but side effects, drug resistance and cost mean that
      better treatments are still needed. Lipid metabolism is closely linked with
      hepatitis C virus (HCV) replication, and endocannabinoids are major regulators of
      lipid homeostasis. The cannabinoid 1 (CB1) receptor mediates these effects in the
      liver. We have previously shown upregulation of CB1 receptors in the livers of
      patients with CHC, and in a HCV cell-culture model. Here, we investigated whether
      CB1 blockade inhibited HCV replication. The antiviral effect of a CB1 antagonist,
      N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamide (AM251), was examined in HCV strain JFH1 cell-culture and subgenomic
      replicon models. The effects on the expression of genes involved in lipid
      metabolism were also measured. CB1 short hairpin RNA (shRNA) was used to confirm
      that the effects were specific for the cannabinoid receptor. Treatment with AM251
      strongly inhibited HCV RNA (~70 %), viral protein (~80 %), the production of new
      virus particles (~70 %) and virus infectivity (~90 %). As expected, AM251 reduced
      the expression of pro-lipogenic genes (SREBP-1c, FASN, SCD1 and ACC1) and
      stimulated genes promoting lipid oxidation (CPT1 and PPARalpha). This effect was
      mediated by AMP-activated protein kinase (AMPK). Stable CB1 knockdown of cells
      infected with HCV showed reduced levels of HCV RNA compared with controls. Thus,
      reduced CB1 signalling inhibits HCV replication using either pharmacological
      inhibitors or CB1 shRNA. This may be due, at least in part, to reduced
      lipogenesis, mediated by AMPK activation. We suggest that CB1 antagonists may
      represent an entirely new class of drug with activity against HCV.

PMID- 25053567
TI  - Towards a phylogeny of the Tenebrionoidea (Coleoptera).
AB  - The phylogenetic relationships of the beetle superfamily Tenebrionoidea are
      investigated using the most comprehensive genetic data set compiled to date. With
      ~34,000 described species in approximately 1250 genera and 28 families,
      Tenebrionoidea represent one of the most diverse and species-rich superfamilies
      of beetles. The interfamilial relationships of the Tenebrionoidea are poorly
      known; previous morphological and molecular phylogenies recovered few well
      supported and often conflicting relationships between families. Here we present a
      molecular phylogeny of Tenebrionoidea based on genes commonly used to resolve
      family and superfamily-level phylogenies of beetles (18S, 28S, 16S, 12S, tRNA Val
      and COI). The alignment spanned over 6.5KB of DNA sequence and over 300
      tenebrionoid genera from 24 of the 28 families were sampled. Maximum Likelihood
      and Bayesian analysis could not resolve deeper level divergences within the
      superfamily and very few relationships between families were supported.
      Increasing gene coverage in the alignment by removing taxa with missing data did
      not improve clade support but when rogue taxa were removed increased resolution
      was recovered. Investigation of signal strength suggested conflicting
      phylogenetic signal was present in the standard genes used for beetle
      phylogenetics, even when rogue taxa were removed. Our study of Tenebrionoidea
      highlights that even with relatively comprehensive taxon sampling within a
      lineage, this standard set of genes is unable to resolve relationships within
      this superfamily. 

PMID- 25053568
TI  - Full-thickness skin graft from the neck for coverage of the radial forearm free
      flap donor site.
AB  - PURPOSE: This study describes the use of a full-thickness skin graft (FTSG) from
      the neck to cover the radial forearm free flap (RFFF) donor site in patients
      undergoing neck dissection and microvascular reconstruction for ablative head and
      neck oncologic surgery. The authors propose that an FTSG from the neck provides
      sufficient tissue quantity and quality, fewer surgical sites, and decreased
      surgical time and cost compared with other FTSG harvest sites and split-thickness
      skin grafts (STSGs). MATERIALS AND METHODS: This was a retrospective study of 50
      patients from 2007 to 2012 who underwent ablative surgery for oral and head and
      neck cancer with concomitant cervical lymphadenectomy and RFFF reconstruction
      with repair of the donor site using an FTSG harvested along the neck dissection
      incision. Patients who underwent donor site repair using other techniques, such
      as ulnar transposition flaps, were excluded. Medical records and perioperative
      photographs were reviewed. RESULTS: Primary closure of the neck without
      dehiscence was achieved in all cases. There were no recipient site infections.
      Minor skin graft loss occurred in a minority of patients and was managed with
      local wound care until healing by secondary intention. No patients required
      surgical revision of the forearm. CONCLUSIONS: An FTSG from the neck provides
      adequate coverage for most RFFF harvests and offers favorable functional and
      esthetic outcomes. The primary advantage is avoiding a third surgical site.
      Complications were comparable to those using FTSGs from other harvest sites.
      Importantly, cross-contamination from the head and neck with the forearm was
      shown not to be an issue.

PMID- 25053569
TI  - Application of modified Karapandzic flaps in large lower lip defect
      reconstruction.
AB  - PURPOSE: Reconstruction of a lower lip defect with a Karapandzic flap often leads
      to greater rounding of the commissure. The aim of this study was to provide a new
      design of bilateral Karapandzic flap for large lower lip defect reconstruction.
      MATERIALS AND METHODS: In this case-series retrospective study, a modification of
      the Karapandzic lip reconstruction technique was used with an additional incision
      to obtain more tissue. The esthetic outcome of the reconstruction was assessed
      using a 4-point scale with regard to the shape of the commissure, lip symmetry,
      appearance of the scar, and lip projection. Functional outcome was assessed by
      speech, preservation of oral competence, lip sensation, facial expression, diet,
      and denture usage. RESULTS: Seventeen patients (13 male, 4 female; age range, 52
      to 82 yr) with squamous cell carcinoma in the lower lip underwent single-stage
      lip reconstruction. Lip defects after tumor resection ranged from 50 to 90% of
      the lower lips. All patients achieved oral competence, without leading to greater
      rounding of the commissure. The esthetic outcome was considered good to excellent
      in 88% of cases and reconstruction did not lead to functional impairments in
      speech, oral competence, lip sensation, facial expression, diet, or denture
      usage. CONCLUSIONS: The modified bilateral Karapandzic flap is a reliable
      technique to reconstruct large lip defects without leading to rounding of the
      commissure. With this technique, good esthetic and functional outcomes can be
      achieved.

PMID- 25053570
TI  - An algorithm for the treatment of isolated zygomatico-orbital fractures.
AB  - PURPOSE: To present algorithms for the treatment of zygomatico-orbital (ZMO)
      fractures and to review how many of our patients were treated using each. We have
      presented 2 algorithms: 1 for when intraoperative computed tomography (CT) scans
      are not available and 1 for when intraoperative CT scans are available. PATIENTS
      AND METHODS: The data from all patients treated by us for isolated, unilateral
      ZMO fractures from January 1991 to December 31, 2013 with adequate medical
      records were retrospectively analyzed. The demographic information and treatment
      methods were collected and tabulated to determine how these patients' fractures
      had been classified using the 2 algorithms. Simple descriptive statistics were
      applied. RESULTS: A total of 883 patients with sufficient records who had
      undergone treatment of isolated, unilateral ZMO fractures were included. Of these
      883 patients, 71 were classified as having high-energy ZMO fractures that had not
      been treated using 1 of the algorithms. A total of 758 patients with sufficient
      records to be included in the present study were treated using the algorithm
      before intraoperative CT scanning was available. Finally, 54 patients were
      treated using the algorithm after intraoperative CT scanning was available. The
      patients were similar demographically. The number of patients treated at each
      point in the algorithms is shown. Overall, only 40% of patients required internal
      orbital reconstruction. CONCLUSIONS: The treatment of most ZMO fractures can be
      sequential, using an algorithm to avoid unnecessary surgical approaches and
      procedures that can potentially cause iatrogenic deformities. The use of
      intraoperative CT scans will allow the surgeon to be less invasive, with greater
      predictability and precision.

PMID- 25053571
TI  - Pressure injury can occur in patients undergoing prolonged head and neck surgery.
AB  - PURPOSE: The aim of this study was to estimate the frequency of and identify the
      risks factors associated with the development of pressure injuries (PIs) in a
      sample of patients who underwent operative treatment of a head and neck
      malignancy. MATERIALS AND METHODS: The sample was composed of patients admitted
      under the care of the Combined Head and Neck Service, John Hunter Hospital from
      2010 to 2012 and whose operation was a minimum of 5 hours duration. The predictor
      variables included a range of demographic, comorbidity, and operative factors.
      The outcome variable was the development of a PI. A multivariate logistic
      regression model was conducted to assess the association between predictor
      variables and the outcome variable (PI). RESULTS: Eighty-eight patients (62 male
      and 26 female) were included in the study. PIs were identified in 13 patients
      (14%). These injuries were typically located over bony prominences, in keeping
      with findings identified in the relevant literature. Specifically, an increased
      risk of PI was seen with decreasing patient age (54.5 +/- 11.6 yr for PI vs 63.1
      + 10.8 yr for no PI; P = .01) and increasing operative duration (729 +/- 79
      minutes for PI vs 625 +/- 158 minutes for no PI; P = .02). CONCLUSIONS: PIs can
      occur in patients who undergo prolonged head and neck resective and
      reconstructive surgery. In particular, decreasing age and increasing operative
      duration were shown to be statistically significant factors in the development of
      PIs in this group of patients.

PMID- 25053572
TI  - Fluorodeoxyglucose positron emission tomography with computed tomography detects
      greater metabolic changes that are not represented by plain radiography for
      patients with osteonecrosis of the jaw.
AB  - PURPOSE: Imaging is important to identify subclinical changes and for treatment
      planning in patients with osteonecrosis of the jaw (ONJ) exposed to
      antiresorptive therapy. The aim of this study was to compare the findings at
      radiography with those at fluorodeoxyglucose (FDG) positron emission tomography
      (PET) with computed tomography (CT) for patients with ONJ related to
      antiresorptive therapy. MATERIALS AND METHODS: A cross-sectional retrospective
      analysis of patients with clinically identified ONJ lesions of the mandible was
      performed. Two imaging modalities were evaluated for each patient: plain
      radiography (ie, panoramic or periapical) and FDG PET/CT with 1-mm sections.
      Outcome variables for the radiographic findings were osteolytic and
      osteosclerotic bone changes. Outcome variables for FDG PET/CT images were
      localization of FDG uptake. Maximum standard uptake values (SUVmax) of abnormal
      FDG jaw uptake were recorded, in addition to the mean SUV of the contralateral
      normal mandible, and used to calculate the target-to-background ratio.
      Radiographic changes and FDG uptake were classified as local (ie, corresponding
      to exposed cortical bone) or diffuse (ie, local changes and changes extending
      beyond the margins of exposed bone) for each imaging technique. Local and diffuse
      changes detected by each imaging modality were described and the difference in
      detection was compared with the McNemar test. RESULTS: Twenty-three patients with
      25 clinically identified ONJ lesions were analyzed using radiography and FDG
      PET/CT. Differences were found in how radiography and FDG PET/CT detect local and
      diffuse changes associated with ONJ. Radiography showed local changes in 17
      patients (68%), diffuse changes in 3 patients (12%), and no changes in 5 patients
      (20%), whereas FDG PET/CT imaging showed local changes in 17 patients (68%) and
      diffuse changes in 8 patients (32%). The McNemar test indicated that FDG PET/CT
      imaging was less likely to miss a lesion (P < .001). Mean SUVmax was 6.59, and
      the mean target-to-background ratio was 5.37. CONCLUSION: The results of this
      study show that FDG PET/CT detects local and diffuse metabolic changes that may
      not be represented by plain radiography for patients with ONJ related to
      antiresorptive therapy. The target-to-background ratio allowed the discrimination
      between ONJ lesions and background changes. Future studies are necessary to
      determine whether FDG PET/CT can determine risk and facilitate management of ONJ.

PMID- 25053573
TI  - Aberrant expression of copper associated genes after copper accumulation in
      COMMD1-deficient dogs.
AB  - BACKGROUND: COMMD1-deficient dogs progressively develop copper-induced chronic
      hepatitis. Since high copper leads to oxidative damage, we measured copper
      metabolism and oxidative stress related gene products during development of the
      disease. METHODS: Five COMMD1-deficient dogs were studied from 6 months of age
      over a period of five years. Every 6 months blood was analysed and liver biopsies
      were taken for routine histological evaluation (grading of hepatitis), rubeanic
      acid copper staining and quantitative copper analysis. Expression of genes
      involved in copper metabolism (COX17, CCS, ATOX1, MT1A, CP, ATP7A, ATP7B, ) and
      oxidative stress (SOD1, catalase, GPX1 ) was measured by qPCR. Due to a sudden
      death of two animals, the remaining three dogs were treated with d-penicillamine
      from 43 months of age till the end of the study. Presented data for time points
      48, 54, and 60 months was descriptive only. RESULTS: A progressive trend from
      slight to marked hepatitis was observed at histology, which was clearly preceded
      by an increase in semi-quantitative copper levels starting at 12 months until 42
      months of age. During the progression of hepatitis most gene products measured
      were transiently increased. Most prominent was the rapid increase in the copper
      binding gene product MT1A mRNA levels. This was followed by a transient increase
      in ATP7A and ATP7B mRNA levels. CONCLUSIONS: In the sequence of events, copper
      accumulation induced progressive hepatitis followed by a transient increase in
      gene products associated with intracellular copper trafficking and temporal
      activation of anti-oxidative stress mechanisms.

PMID- 25053574
TI  - Correlations among antiangiogenic factors and trace elements in hypertensive
      disorders of pregnancy.
AB  - Although a number of studies have measured circulating levels of some trace
      elements in preeclampsia (PE) and compared to healthy pregnant (HP), there is no
      consensus yet about the deficiency of some metals and development of hypertensive
      disorders in pregnancy. The aim of this study was to compare plasmatic levels of
      Zn, Mn, Co, Cu, Se and Sr among non-pregnant (NP), healthy pregnant (HP),
      gestational hypertensive (GH) and preeclamptic (PE) women and to correlate these
      levels with plasma soluble endoglin (sENG) and soluble fms-like tyrosine kinase-1
      (sFLT-1), two important antiangiogenic proteins related to PE. A total of 184
      women were enrolled in this study (NP=35, GH=51, PE=37 and HP=61). Trace element
      analyses were carried out with an inductively coupled plasma mass spectrometer
      (ICPMS). sENG and sFLT-1 plasma concentrations were measured by commercial ELISA
      kits. The most interesting result is that Sr is higher in PE (63%, P<0.001)
      compared to HP and their levels are positively correlated with sENG in all three
      groups of pregnant women. Moreover, we found a negative correlation between Zn
      and sENG in HP (r=-0.43, P=0.003). Regarding other elements, we found similar
      levels among pregnant groups. In conclusion, this study showed that Sr may has a
      role in physiopathology of PE. 

PMID- 25053575
TI  - Sexual differentiation anomalies. XX male syndrome.

PMID- 25053576
TI  - Depuration of metals by the green-colored oyster Crassostrea sikamea.
AB  - The accumulation of metals (especially copper) in oysters has led to green-color
      now being found in Chinese estuaries. In the present study, the authors
      quantified the depuration of 8 metals (Ag, Cd, Co, Cr, Cu, Ni, Pb, and Zn) in
      green-colored oysters (Crassostrea sikamea) collected from an estuary that is
      heavily contaminated by metals as a result of industrial effluent releases. The
      oysters were depurated under laboratory conditions for 4 mo; the accumulated
      concentrations and the subcellular distribution of metals were measured at
      different time intervals. Results showed that the green color of oysters faded to
      light yellow (nearly normal) after 4 mo of depuration. Depuration of metals could
      be described by a first-order kinetic process. The calculated overall depuration
      rate constants of metals were in the range of 0.008 d(-1) to 0.024 d(-1) , with a
      biological retention half-life of 30 d to 70 d. The depuration rates of green
      colored contaminated oysters were significantly higher for Cd, Cu, Cr, and Ni
      than the rates of oysters from a less contaminated site, whereas the depuration
      rates of Ag, Co, Pb, and Zn were comparable between the 2 populations. When
      corrected for the change of oyster tissue weight, the actual efflux rate
      constants of the metals (0.0708-0.1014 d(-1) ) were much higher than the overall
      depuration rate constants. Cellular debris and metallothionein-like proteins were
      the important fractions binding with the metals in the oysters. Significant
      changes in metal subcellular distribution were observed during the 4-mo
      depuration for Ag, Cd, Cu, and Zn. Metallothionein-like protein became more
      important in sequestering the metals during the depuration period, with a
      concomitant decrease in metals associated with the cellular debris fraction.

PMID- 25053578
TI  - Assessment of administrative claims data for public health reporting of
      Salmonella in Tennessee.
AB  - In the USA, approximately 4% of the estimated 1 million Salmonella infections
      occurring annually are reported to public health. Administrative claims data from
      large health insurance companies capture disease-specific data which could
      potentially enhance public health surveillance. To determine the utility of
      medical claims data for public health reporting of Salmonella, we assessed
      medical claims data from BlueCross BlueShield of Tennessee (BCBST) members
      compared to Tennessee Department of Health (TDH) surveillance data. BCBST
      Salmonella cases diagnosed during 2007-2011 were matched to TDH Salmonella cases
      reported during the same time period. Matches and non-matches were validated
      using medical records. Of the 450 BCBST cases identified, 72% matched TDH cases.
      All culture-confirmed BCBST cases were reported to TDH. Non-matched BCBST cases
      included clinical diagnoses which were culture negative or not tested. Our
      findings indicate administrative claims data are not currently a viable mechanism
      for enhancing routine reporting of Salmonella infections. 

PMID- 25053577
TI  - Validating drug repurposing signals using electronic health records: a case study
      of metformin associated with reduced cancer mortality.
AB  - OBJECTIVES: Drug repurposing, which finds new indications for existing drugs, has
      received great attention recently. The goal of our work is to assess the
      feasibility of using electronic health records (EHRs) and automated informatics
      methods to efficiently validate a recent drug repurposing association of
      metformin with reduced cancer mortality. METHODS: By linking two large EHRs from
      Vanderbilt University Medical Center and Mayo Clinic to their tumor registries,
      we constructed a cohort including 32,415 adults with a cancer diagnosis at
      Vanderbilt and 79,258 cancer patients at Mayo from 1995 to 2010. Using automated
      informatics methods, we further identified type 2 diabetes patients within the
      cancer cohort and determined their drug exposure information, as well as other
      covariates such as smoking status. We then estimated HRs for all-cause mortality
      and their associated 95% CIs using stratified Cox proportional hazard models. HRs
      were estimated according to metformin exposure, adjusted for age at diagnosis,
      sex, race, body mass index, tobacco use, insulin use, cancer type, and non-cancer
      Charlson comorbidity index. RESULTS: Among all Vanderbilt cancer patients,
      metformin was associated with a 22% decrease in overall mortality compared to
      other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39%
      decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI
      0.50 to 0.73). Diabetic patients on metformin also had a 23% improved survival
      compared with non-diabetic patients (HR 0.77; 95% CI 0.71 to 0.85). These
      associations were replicated using the Mayo Clinic EHR data. Many site-specific
      cancers including breast, colorectal, lung, and prostate demonstrated reduced
      mortality with metformin use in at least one EHR. CONCLUSIONS: EHR data suggested
      that the use of metformin was associated with decreased mortality after a cancer
      diagnosis compared with diabetic and non-diabetic cancer patients not on
      metformin, indicating its potential as a chemotherapeutic regimen. This study
      serves as a model for robust and inexpensive validation studies for drug
      repurposing signals using EHR data.

PMID- 25053579
TI  - An integrative framework for sensor-based measurement of teamwork in healthcare.
AB  - There is a strong link between teamwork and patient safety. Emerging evidence
      supports the efficacy of teamwork improvement interventions. However, the
      availability of reliable, valid, and practical measurement tools and strategies
      is commonly cited as a barrier to long-term sustainment and spread of these
      teamwork interventions. This article describes the potential value of sensor
      based technology as a methodology to measure and evaluate teamwork in healthcare.
      The article summarizes the teamwork literature within healthcare, including team
      improvement interventions and measurement. Current applications of sensor-based
      measurement of teamwork are reviewed to assess the feasibility of employing this
      approach in healthcare. The article concludes with a discussion highlighting
      current application needs and gaps and relevant analytical techniques to overcome
      the challenges to implementation. Compelling studies exist documenting the
      feasibility of capturing a broad array of team input, process, and output
      variables with sensor-based methods. Implications of this research are summarized
      in a framework for development of multi-method team performance measurement
      systems. Sensor-based measurement within healthcare can unobtrusively capture
      information related to social networks, conversational patterns, physical
      activity, and an array of other meaningful information without having to directly
      observe or periodically survey clinicians. However, trust and privacy concerns
      present challenges that need to be overcome through engagement of end users in
      healthcare. Initial evidence exists to support the feasibility of sensor-based
      measurement to drive feedback and learning across individual, team, unit, and
      organizational levels. Future research is needed to refine methods, technologies,
      theory, and analytical strategies. 

PMID- 25053581
TI  - Differential regulation of amyloid precursor protein sorting with pathological
      mutations results in a distinct effect on amyloid-beta production.
AB  - The deposition of amyloid-beta (Abeta) peptide, which is generated from amyloid
      precursor protein (APP), is the pathological hallmark of Alzheimer's disease
      (AD). Three APP familial AD mutations (D678H, D678N, and H677R) located at the
      sixth and seventh amino acid of Abeta have distinct effect on Abeta aggregation,
      but their influence on the physiological and pathological roles of APP remain
      unclear. We found that the D678H mutation strongly enhances amyloidogenic
      cleavage of APP, thus increasing the production of Abeta. This enhancement of
      amyloidogenic cleavage is likely because of the acceleration of APPD678H sorting
      into the endosomal-lysosomal pathway. In contrast, the APPD678N and APPH677R
      mutants do not cause the same effects. Therefore, this study indicates a
      regulatory role of D678H in APP sorting and processing, and provides genetic
      evidence for the importance of APP sorting in AD pathogenesis. The
      internalization of amyloid precursor protein (APP) increases its opportunity to
      be processed by beta-secretase and to produce Amyloid-beta (Abeta) that causes
      Alzheimer's disease (AD). We report a pathogenic APPD678H mutant that enhances
      APP internalization into the endosomal-lysosomal pathway and thus promotes the
      beta-secretase cleavage and Abeta production. This study provides genetic
      evidence for the importance of APP sorting in AD pathogenesis. 

PMID- 25053580
TI  - Directing the public to evidence-based online content.
AB  - To direct online users searching for gynecologic cancer information to accurate
      content, the Centers for Disease Control and Prevention's (CDC) 'Inside
      Knowledge: Get the Facts About Gynecologic Cancer' campaign sponsored search
      engine advertisements in English and Spanish. From June 2012 to August 2013,
      advertisements appeared when US Google users entered search terms related to
      gynecologic cancer. Users who clicked on the advertisements were directed to
      relevant content on the CDC website. Compared with the 3 months before the
      initiative (March-May 2012), visits to the CDC web pages linked to the
      advertisements were 26 times higher after the initiative began (June-August 2012)
      (p<0.01), and 65 times higher when the search engine advertisements were
      supplemented with promotion on television and additional websites (September 2012
      August 2013) (p<0.01). Search engine advertisements can direct users to evidence
      based content at a highly teachable moment--when they are seeking relevant
      information.

PMID- 25053582
TI  - Psychological characteristics, eating behavior, and quality of life assessment of
      obese patients undergoing weight loss interventions.
AB  - BACKGROUND AND AIMS: Bariatric surgery is the most effective treatment for
      obesity. However, not all patients have similar weight loss following surgery and
      many researchers have attributed this to different pre-operative psychological,
      eating behavior, or quality-of-life factors. The aim of this study was to
      determine whether there are any differences in these factors between patients
      electing to have bariatric surgery compared to less invasive non-surgical weight
      loss treatments, between patients choosing a particular bariatric surgery
      procedure, and to identify whether these factors predict weight loss after
      bariatric surgery. MATERIAL AND METHODS: This was a prospective study of 90
      patients undergoing gastric bypass, vertical sleeve gastrectomy, or adjustable
      gastric banding and 36 patients undergoing pharmacotherapy or lifestyle
      interventions. All patients completed seven multi-factorial psychological, eating
      behavior, and quality-of-life questionnaires prior to choosing their weight loss
      treatment. Questionnaire scores, baseline body mass index, and percent weight
      loss at 1 year after surgical interventions were recorded. RESULTS AND
      CONCLUSIONS: Surgical patients were younger, had a higher body mass index, and
      obesity had a higher impact on their quality of life than on non-surgical
      patients, but they did not differ in the majority of eating behavior and
      psychological parameters studied. Patients opting for adjustable gastric banding
      surgery were more anxious, depressed, and had more problems with energy levels
      than those choosing vertical sleeve gastrectomy, and more work problems compared
      to those undergoing gastric bypass. Weight loss after bariatric surgery was
      predicted by pre-operative scores of dietary restraint, disinhibition, and pre
      surgery energy levels. The results of this study generate a number of hypotheses
      that can be explored in future studies and accelerate the development of
      personalized weight loss treatments.

PMID- 25053583
TI  - Factors associated with in-hospital outcomes in 594 consecutive patients
      suffering from severe blunt chest trauma.
AB  - BACKGROUND AND AIMS: Blunt thoracic injury is a common cause for hospital
      admission after trauma. The effect of the number of rib fractures on the outcome
      is controversial. In this study, our hypothesis was that an increasing number of
      rib fractures correlates with mortality and hospital resource utilization. In
      addition to mortality, our focus was on the length of stay at hospital and in the
      intensive care unit, ventilator days, and the days in continuous positive airway
      pressure. MATERIAL AND METHODS: The present investigation is a retrospective
      study from a single trauma center. The study includes patients with severe
      thoracic injury (thoracic Abbreviated Injury Scale (AIS) > 2) admitted to
      hospital after blunt trauma. Patients with isolated thoracic spine injuries and
      patients who were dead on arrival were excluded. Vital signs, laboratory results
      on admission, given care, intensive care unit and hospital length of stay,
      injuries, and in-hospital mortality were collected for the study. RESULTS: A
      total of 594 patients from a 5-year period (2003-2007) were included in the
      study. The mean age of the patients was 45 years, and 76.9% of the patients were
      males. The average Injury Severity Score was 22, and the patients had on average
      5.5 injuries. Overall mortality was 6.4%. In the multivariate analysis, the
      mortality was associated with base excess and tromboplastin time in admission.
      The number of rib fractures did not correlate with the outcome measures, but the
      presence of bilateral rib fractures correlated with the outcome measures other
      than mortality. CONCLUSIONS: The number of rib fractures does not correlate with
      mortality or the length of stay in the intensive care unit in blunt trauma
      patients with severe thoracic injury. Mortality in these patients correlated with
      the degree of hypoperfusion (base excess) and coagulation abnormalities
      (tromboplastin time) on admission.

PMID- 25053584
TI  - Risk factors for the periprosthetic fracture after total hip arthroplasty: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: A systematic review and meta-analysis was performed to
      investigate the risk factors associated with periprosthetic fracture after total
      hip arthroplasty. MATERIAL AND METHODS: We searched potential studies in the
      following databases: MEDLINE, Embase, Web of Science, SCOPUS and Cochrane CENTRAL
      up to December 2013. Newcastle-Ottawa Scale was used to evaluate the
      methodological quality, and Stata 11.0 was used to perform all the analyses.
      RESULTS: Seven studies altogether, including 1069 cases of periprosthetic
      fractures and 74,776 controls, were included in the meta-analysis. Compared to
      those absent following demographic or medical conditions, patients involved with
      female gender (odds ratio, 1.534; p < 0.001), advanced age (>80) (odds ratio:
      4.203; p < 0.001), revision (odds ratio: 4.398; p < 0.001), rheumatoid arthritis
      (odds ratio: 2.503; p < 0.001), osteonecrosis (odds ratio: 1.563; p = 0.009), and
      implant type of Exeter (odds ratio: 1.511; p = 0.017) were more likely to sustain
      periprosthetic fractures. Osteoarthritis (vs not) (odds ratio: 0.449; p < 0.001)
      was identified a protective factor for periprosthetic fractures after total hip
      arthroplasty. The other factors, including lower ages, American Society of
      Anesthesiologists >= 3, and other implant types, were not significant risk
      factors for periprosthetic fractures. CONCLUSIONS: These medical conditions as
      reminder should be kept in clinicians' mind and close follow-up should be
      implemented in patients involved for preventing the occurrence of periprosthetic
      fractures after total hip arthroplasty.

PMID- 25053586
TI  - Differential transcriptome analysis of diabetes-resistant and -sensitive mouse
      islets reveals significant overlap with human diabetes susceptibility genes.
AB  - Type 2 diabetes in humans and in obese mice is polygenic. In recent genome-wide
      association studies, genetic markers explaining a small portion of the genetic
      contribution to the disease were discovered. However, functional evidence linking
      these genes with the pathogenesis of diabetes is scarce. We performed RNA
      sequencing-based transcriptomics of islets from two obese mouse strains, a
      diabetes-susceptible (NZO) and a diabetes-resistant (B6-ob/ob) mouse, after a
      short glucose challenge and compared these results with human data. Alignment of
      2,328 differentially expressed genes to 106 human diabetes candidate genes
      revealed an overlap of 20 genes, including TCF7L2, IGFBP2, CDKN2A, CDKN2B, GRB10,
      and PRC1. The data provide a functional validation of human diabetes candidate
      genes, including those involved in regulating islet cell recovery and
      proliferation, and identify additional candidates that could be involved in human
      beta-cell failure.

PMID- 25053585
TI  - Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key
      role in the development of metabolic syndrome phenotype.
AB  - Obesity is often regarded as the primary cause of metabolic syndrome. However,
      many lines of evidence suggest that obesity may develop as a protective mechanism
      against tissue damage during caloric surplus and that it is only when the maximum
      fat accumulation capacity is reached and fatty acid spillover occurs into to
      peripheral tissues that metabolic diseases develop. In this regard, identifying
      the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid
      spillover is imperative. Here we identify the deleted in breast cancer 1 (DBC1)
      protein as a key regulator of fat storage capacity of adipocytes. We found that
      knockout (KO) of DBC1 facilitated fat cell differentiation and lipid accumulation
      and increased fat storage capacity of adipocytes in vitro and in vivo. This
      effect resulted in a "healthy obesity" phenotype. DBC1 KO mice fed a high-fat
      diet, although obese, remained insulin sensitive, had lower free fatty acid in
      plasma, were protected against atherosclerosis and liver steatosis, and lived
      longer. We propose that DBC1 is part of the molecular machinery that regulates
      fat storage capacity in adipocytes and participates in the "turn-off" switch that
      limits adipocyte fat accumulation and leads to fat spillover into peripheral
      tissues, leading to the deleterious effects of caloric surplus.

PMID- 25053587
TI  - Glucose-dependent insulinotropic polypeptide augments glucagon responses to
      hypoglycemia in type 1 diabetes.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is glucagonotropic, and
      glucagon-like peptide-1 (GLP-1) is glucagonostatic. We studied the effects of GIP
      and GLP-1 on glucagon responses to insulin-induced hypoglycemia in patients with
      type 1 diabetes mellitus (T1DM). Ten male subjects with T1DM (C-peptide negative,
      age [mean +/- SEM] 26 +/- 1 years, BMI 24 +/- 0.5 kg/m(2), HbA1c 7.3 +/- 0.2%)
      were studied in a randomized, double-blinded, crossover study, with 2-h
      intravenous administration of saline, GIP, or GLP-1. The first hour, plasma
      glucose was lowered by insulin infusion, and the second hour constituted a
      "recovery phase." During the recovery phase, GIP infusions elicited larger
      glucagon responses (164 +/- 50 [GIP] vs. 23 +/- 25 [GLP-1] vs. 17 +/- 46 [saline]
      min ? pmol/L, P < 0.03) and endogenous glucose production was higher with GIP and
      lower with GLP-1 compared with saline (P < 0.02). On the GIP days, significantly
      less exogenous glucose was needed to keep plasma glucose above 2 mmol/L (155 +/-
      36 [GIP] vs. 232 +/- 40 [GLP-1] vs. 212 +/- 56 [saline] mg ? kg(-1), P < 0.05).
      Levels of insulin, cortisol, growth hormone, and noradrenaline, as well as
      hypoglycemic symptoms and cognitive function, were similar on all days. Our
      results suggest that during hypoglycemia in patients with T1DM, exogenous GIP
      increases glucagon responses during the recovery phase after hypoglycemia and
      reduces the need for glucose administration.

PMID- 25053588
TI  - Type 2 diabetes, skin autofluorescence, and brain atrophy.
AB  - Type 2 diabetes mellitus (T2DM) is associated with brain atrophy, but the
      mechanisms underlying this link are unknown. Advanced glycation end products
      (AGEs) accumulate in T2DM, resulting in inflammation, oxidative stress, and
      protein cross-linking, which are known contributors to neurodegeneration. We
      aimed to study whether tissue AGE accumulation is associated with T2DM-related
      brain atrophy. We performed brain magnetic resonance imaging, cognitive tests,
      and noninvasive skin autofluorescence (SAF; a measure of tissue AGE levels) on
      people aged >55 years with and without T2DM. Multivariable linear regression was
      used to study the relationships among T2DM, SAF, and gray matter volume (GMV).
      There were 486 people included in the study. T2DM was associated with greater
      SAF. Greater SAF, T2DM, and cognitive impairment were each associated with lower
      GMV independently of age, sex, and total intracranial volume. SAF partially
      mediated the association between T2DM and GMV. Longitudinal studies may help
      confirm whether tissue AGE accumulation is associated with brain atrophy in T2DM.

PMID- 25053589
TI  - Inducing sustained oscillations in feedback-linearizable single-input nonlinear
      systems.
AB  - The present paper concerns the induction of stable sustained oscillation in
      feedback-linearizable single-input affine nonlinear dynamical systems via
      continuous-time state feedback control. The proposed application-oriented control
      approach is based on the conception of a state feedback controller that ensures
      the tracking of a limit cycle characterized in terms of the feedback-linearized
      system. Boundedness and convergence of the closed-loop trajectories are
      established following the Lyapunov theoretical framework and applying LaSalle's
      stability principle. The proposed approach is demonstrated with computer
      simulated control experiments, showing that it ensures the convergence of the
      state trajectories of the controlled system to a designed limit cycle and that
      the methodology can, in principle, be applied to any single input feedback
      linearizable system.

PMID- 25053590
TI  - National evaluation of prescriber drug dispensing.
AB  - OBJECTIVE: To describe the legal, professional, and consumer status of
      prescribers dispensing legend and over-the-counter drugs in the United States.
      METHODS: Legal and academic databases were searched to identify those states that
      permit prescribers to dispense medications to patients and any limitations on
      such practice. In addition, prescribers and patients-consumers were surveyed to
      learn about the prevalence and perceptions of such practice. The use of drug
      samples was explicitly excluded from the study. MAIN RESULTS: Surveys were
      obtained from 556 physicians, 64 NPs, and 999 patient-consumers of drugs
      dispensed by prescribers. Forty-four states authorize prescriber dispensing.
      Midlevel practitioners (i.e., NPs and physician assistants) are authorized to
      dispense in 43 states. Thirty-two states do not require dispensing prescribers to
      compete additional registration to dispense medications, and 30 states require
      some level of compliance with pharmacy practice requirements. Prescriber
      dispensing is common, independent of patient age or insurance coverage.
      Prescriber dispensing appears driven by physician and patient perceptions of
      convenience and cost reductions. Future dispensing is likely to increase due to
      consumers' satisfaction with the practice. Consumer self-reported adverse drug
      reactions (ADRs) were equivalent between pharmacist- and physician-dispensed
      drugs, but urgent and emergency clinic ADR consultations were slightly lower with
      physician dispensing. CONCLUSIONS: Prescriber dispensing is firmly entrenched in
      the U.S. health care system, is likely to increase, does not appear to increase
      ADRs, and may reduce urgent care and emergency department visits. The reduction
      in urgent care and emergency department visits requires further study to confirm
      these preliminary findings.

PMID- 25053591
TI  - Melittin enhances radiosensitivity of hypoxic head and neck squamous cell
      carcinoma by suppressing HIF-1alpha.
AB  - Hypoxia is a widespread phenomenon present in many human solid tumors and is
      associated with a poor prognosis and therapy resistance. Here, we tested the
      feasibility of melittin, a major component of bee venom, on radiosensitization of
      hypoxic head and neck squamous cell carcinoma (HNSCC). CNE-2 and KB cells were
      treated with melittin and radiation response was determined. Cell viability,
      cytotoxicity and apoptosis induction were examined by CCK-8 assay, colony
      formation assay, and flow cytometry. Expression of hypoxia-inducible factor 1
      alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) proteins were
      assessed using western blotting. Additionally, we also examined the effect of
      melittin on tumor growth and radiosensitivity in vivo using a xenograft model of
      HNSCC. Treatment with melittin resulted in cell growth inhibition, induction of
      cell apoptosis, and reduction of HIF-1alpha and VEGF expression, which has been
      linked to hypoxia cell radioresistance. In addition, intraperitoneal injection of
      melittin significantly reduced the growth of HNSCC tumors in CNE-2 tumor-bearing
      mice. These data suggest that melittin enhances radiosensitivity of HNSCC under
      hypoxia condition, and this is associated with the suppression of HIF-1alpha
      expression. Melittin appears to be a potential radiotherapy sensitization agent
      due to its significant antihypoxia activity. 

PMID- 25053592
TI  - Systematic review of high-dose and standard-dose chemotherapies in the treatment
      of primary well-differentiated osteosarcoma.
AB  - The objective of this study is to evaluate whether high-dose chemotherapy is more
      efficacious than standard-dose chemotherapy in the treatment of primary well
      differentiated osteosarcoma. The Cochrane systematic evaluation method was
      adopted. A database search was conducted in MEDLINE, Embase, OVID, the Cochrane
      Central Register of Controlled Trials database and the Chinese Biomedical
      Literature CD-ROM Database. The quality of the included studies was jointly
      evaluated by two reviewers, and homogeneous studies were included for meta
      analysis. A total of five studies were included in this meta-analysis, with 1,415
      subjects with primary, nonmetastatic, well-differentiated osteosarcoma in the
      limbs. No statistically significant differences were found between the high-dose
      chemotherapy group and the low-dose group in 5-year event-free survival [RR 1.04,
      95 %CI (0.95, 1.13)], 5-year overall survival [RR 1.02, 95 %CI (0.95, 1.10)],
      local recurrence rate [RR 0.90, 95 %CI (0.59, 1.39)], proportion of subjects with
      good histological response [RR 0.93, 95 %CI (0.81, 1.07)], or limb salvage rate
      [RR 0.97, 95 %CI (0.92, 1.02)]. A statistically significant difference was
      observed in the 5-year event-free survival between the subjects with good
      histological response to preoperative chemotherapy and the subjects with poor
      histological response [RR 1.55, 95 %CI (1.19, 2.00), P < 0.001]. High-dose
      chemotherapy did not show superior efficacy to low-dose chemotherapy in the
      treatment of primary well-differentiated osteosarcoma. Further high-quality
      randomized controlled trials are needed to provide additional reliable evidence
      for our observation.

PMID- 25053594
TI  - Variation risks of SFRP2 hypermethylation between precancerous disease and
      colorectal cancer.
AB  - DNA hypermethylation of secreted frizzled-related protein 2 (SFRP2) gene
      associated with the Wnt signaling pathway has been studied previously. However,
      the risk size and changing rules between colorectal cancer (CRC) and SFRP2
      hypermethylation from precancerous disease to CRC remain unclear. The aim of work
      was therefore to investigate the risk size and changing rule based on detections
      on large numbers of tissue and feces samples. Association study and meta-analysis
      were performed to analyze the risk size of SFRP2 hypermethylation in tissue and
      fecal detections from 2,912 samples, including 1,436 patients with CRC, 866
      patients with colon adenomas or polyps, and 610 samples with both normal
      controls. Based on normal controls as standard reference, the analysis showed
      that SFRP2 hypermethylation in CRC and adenoma tissues had a significantly higher
      risk with 92.81 (28.76-299.45) and 22.46 (4.13-122.04) odds ratio (OR) (95 %
      confidence interval (CI)) respectively, and that the risk sizes of SFRP2
      hypermethylation in CRC and adenoma patients were 41.86 (18.91-92.67) and 11.76
      (6.98-19.84) of OR (95 % CI) in fecal samples, and that the OR risk in both
      tissue and fecal samples increased significantly to 70.35 and 30.10 from
      precancerous disease (adenoma or polyp) to CRC. There were significant
      differences between tissue and fecal hypermethylation frequency. On the basis of
      the hypermethylation frequency of colorectal tissue, the coincidence rates of
      fecal hypermethylation in CRC and colorectal adenoma were 0.89 and 0.9,
      respectively. The risk size of SFRP2 hypermethylation from normal control to
      adenoma or polyp as well as from adenoma or polyp to CRC increased gradually in
      both tissue and feces. Therefore, SFRP2 hypermethylation is an important
      biomarker both in noninvasive diagnosis in feces detection and in colon tissue.

PMID- 25053593
TI  - Meta-analyses of methylation markers for prostate cancer.
AB  - Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous cancer that
      has become the sixth leading cause of mortality in both the developed and
      developing countries. Accumulating evidence showed a number of genes with
      aberrant DNA methylation in the pathogenesis of PCa. Here, we conducted a
      systematic meta-analysis to evaluate the contribution of aberrantly methylated
      genes to the risk of PCa. Relevant methylation studies were retrieved from PubMed
      and Wanfang literature databases. In the meta-analysis, Mantel-Haenszel odds
      ratios (ORs) and 95 % confidence intervals (CIs) were calculated for each
      methylation event under appropriate models. A total of 594 publications were
      initially retrieved from PubMed and Wanfang literature database. After a three
      step filtration, we harvested 39 case-control articles investigating the role of
      gene methylation in the prediction of PCa risk. Among the 31 genes involved, 24
      genes were shown to be significantly hypermethylated in the PCa patients. Our
      meta-analyses identified strong associations of four aberrantly methylated genes
      (GSTP1, RASSF1, p16, and RARB) with PCa. Further research is needed to strengthen
      our findings in the future.

PMID- 25053595
TI  - MicroRNAs as ideal biomarkers for the diagnosis of lung cancer.
AB  - Lung cancer (LC) is one of the most prevalent causes of cancer death with a high
      mortality rate worldwide. While various sets of microRNAs (miRNAs) have been
      found to be highly sensitive and specific biomarkers for the early diagnosis of
      LC (the first word of abstract), conflicting results on their diagnostic accuracy
      are still present in individual studies. Thus, we aimed to conduct a systematic
      review and meta-analysis of the published literature to comprehensively assess
      the diagnostic value of miRNAs for predicting LC. The sensitivity and specificity
      of each included study were used to plot the summary receiver operator
      characteristic (SROC) curve and to calculate the area under the SROC curve (AUC).
      All analyses were performed using the Stata 12.0 software. Twenty-six articles
      were involved in our meta-analysis, 18 of which focused on single miRNA assays
      and 15 on multiple miRNA assays. For single miRNA profiling, the pooled
      parameters calculated from all studies are as follows: sensitivity (SEN), 0.72;
      specificity (SPE), 0.74; positive likelihood ratio (PLR), 2.7; negative
      likelihood ratio (NLR), 0.39; and diagnostic odds ratio (DOR), 7. For multiple
      miRNA profiling, the pooled estimates for the overall studies are as follows:
      SEN, 0.81; SPE, 0.84; PLR, 4.9; NLR, 0.23; and DOR, 22, which are significantly
      better than the diagnostic performance of the single miRNA profiling. In
      addition, subgroup analyses based on sample types suggested that blood-based
      multiple miRNA assays were more accurate than non-blood-based studies. In
      conclusion, the current meta-analysis shows that multiple miRNA assays were more
      accurate in diagnosing LC than single miRNA assays. However, further large-scale
      investigations are urgently needed to confirm our results and verify the
      feasibility of routine clinical utilization.

PMID- 25053596
TI  - Up-regulation of flotillin-2 is associated with renal cell carcinoma progression.
AB  - Flotillin-2 (FLOT2) is a highly conserved protein isolated from caveolae/lipid
      raft domains that tether growth factor receptors linked to signal transduction
      pathway. FLOT2 has recently been identified to be involved in tumorigenesis of
      several cancers such as breast cancer, melanoma, and gastric cancer. However, the
      role of FLOT2 in renal cell carcinoma (RCC) remains unclear. The expression
      levels of FLOT2 in RCC patients and renal cancer cell lines were evaluated by
      quantitative real-time PCR (qRT-PCR) and Western blot. FLOT2 protein expression
      was also analyzed in archived paraffin-embedded RCC tissues using
      immunohistochemistry (IHC), and its association with overall survival of patients
      was analyzed by statistical analysis. Small-interfering RNA (siRNA) was used to
      suppress FLOT2 expression in RCC cell lines. In vitro assays were performed to
      further explore its role in tumor progression. The expression level of FLOT2 was
      higher in RCC tissues and cell lines than in corresponding adjacent normal
      tissues and normal human proximal tubule epithelial cell line HK-2. IHC analysis
      revealed high expression levels of FLOT2 in RCC specimens. The RCC patients with
      higher FLOT2 expression had an advanced clinical stage and poorer prognosis than
      those with lower FLOT2 expression. FLOT2 expression was an independent prognostic
      marker of overall RCC patient survival in a multivariate analysis. In vitro
      assays indicated that knockdown of FLOT2 reduced cell proliferation, migration,
      and invasion. Our data suggest that FLOT2 is a novel molecule involved in RCC
      progression, which provide a potential prognostic biomarker and therapeutic
      target.

PMID- 25053597
TI  - Expression of metabolism-related proteins in invasive lobular carcinoma:
      comparison to invasive ductal carcinoma.
AB  - The purpose of this study is to investigate the difference in expression of
      metabolism-related proteins in invasive lobular carcinoma (ILC) compared to those
      of the invasive ductal carcinoma (IDC). Tissue microarray was manufactured for
      114 cases of ILC and 692 cases of IDC. Immunohistochemical stains were performed
      as follows: glycolysis (Glut-1, hexokinase II, CAIX, MCT4), glutaminolysis (GLS1,
      GDH, ASCT2), mitochondria (ATP synthase, SDHA, SDHB), and serine/glycine
      metabolism (PHGDH, PSAT1, PSPH, SHMT1, GLDC) related proteins. Pleomorphic type
      (n = 12) of ILC revealed higher expression in hexokinase II, SDHB, and GLDC than
      classic type (n = 102) (p < 0.05). IDC showed a higher expression of glycolysis
      (Glut-1, CAIX, MCT4), glutaminolysis (GLS1, ASCT2), and serine/glycine metabolism
      (PSPH, SHMT1, GLDC) related protein than ILC in tumor cells, whereas ILC revealed
      higher expression in GDH, SDHA, PHGDH, and PSAT1 than IDC in tumor cells (p <
      0.05). In addition, IDC demonstrated a higher expression of metabolism-related
      proteins than ILC in stromal tissue (p < 0.05). In ILC, tumoral GLDC positivity
      was correlated with higher nuclear grade (p = 0.026) and higher histologic grade
      (p = 0.026), and tumoral Glut-1 positivity correlated with higher histologic
      grade (p = 0.026). Additionally, tumoral PSPH positivity showed a significant
      correlation to ER negativity and PR negativity (p = 0.026). In conclusion, it
      reveals different expression patterns of metabolism-related proteins between IDC
      and ILC.

PMID- 25053598
TI  - LPS promotes epithelial-mesenchymal transition and activation of TLR4/JNK
      signaling.
AB  - The endotoxin level in the portal and peripheral veins of hepatocellular
      carcinoma (HCC) patients is higher and lipopolysaccharide (LPS), has been
      reported to inhibit tumor growth. However, in this study, we found that LPS
      induced Toll-like receptor 4 (TLR4) signaling was involved in tumor invasion and
      the molecular mechanism was investigated. The HCC cells were used to study the
      invasion ability of LPS-induced HCC cells and the epithelial-mesenchymal
      transition (EMT) in vitro. The in vitro experiments demonstrated that LPS could
      significantly enhance the invasive potential and induce EMT in HCC cells with
      TLR4 dependent. Further studies showed that LPS could directly activate JNK/MAPK
      signaling through TLR4 in HCC cells. Interestingly, blocking JNK/MAPK signaling
      significantly inhibited EMT occurrence. Our results indicate that TLR4/JNK/MAPK
      signaling is required for LPS-induced EMT, tumor cell invasion and metastasis,
      which provide molecular insights for LPS-related pathogenesis and a basis for
      developing new strategies against metastasis in HCC.

PMID- 25053599
TI  - Risk/benefit profile of panitumumab-based therapy in patients with metastatic
      colorectal cancer: evidence from five randomized controlled trials.
AB  - This study aims to evaluate the risk and benefit profiles of panitumumab-based
      therapy (PBT) in patients with metastatic colorectal cancer (mCRC). Relevant
      randomized controlled trials were identified by searching PubMed, Medline, EMBASE
      and Cochrane Library. Data on progression-free survival (PFS), overall survival
      (OS), all grade and severe (grade >=3) adverse events were extracted and pooled
      to calculate hazard ratios (HRs) and risk ratios (RRs) with 95 % confidence
      intervals (CIs). Number needed to treat (NNT) for PFS and number needed to harm
      (NNH) for significantly changed toxicities were calculated. A total of 4,155
      patients were included in the analysis. PBT significantly improved PFS (HRrandom
      = 0.66, 95 % CI = 0.45-0.95) but not OS (HRfixed = 0.93, 95 % CI = 0.83-1.04)
      when used in the subsequent-line setting. The effect on PFS was more evident in
      patients with wild-type KRAS (HRrandom = 0.64, 95 % CI = 0.47-0.87) and the NNT
      for PFS is 11 to 23at 1 year. PBT did not benefit patients when used in the first
      line setting. In addition, PBT significantly increased the risk of skin toxicity,
      infections, diarrhea, dehydration, mucositis, hypokalemia, fatigue,
      hypomagnesemia, pulmonary embolism and paronychia. The NNHs for skin toxicity,
      diarrhea, infection, hypokalemia and mucositis are less than 23. In conclusion,
      when used in the subsequent-line setting, PBT can improve the disease
      progression, especially in mCRC patients with wild-type KRAS. Regarding the
      adverse events associated with the PBT, close monitoring and necessary
      preparations are recommended during the therapy.

PMID- 25053600
TI  - Preoperative predicting score of lymph node metastasis for gastric cancer.
AB  - The aim of our study was to develop a new score system that might predict the
      probability of lymph node of gastric carcinoma. We studied the
      clinicopathological variables of 932 patients with gastric carcinoma admitted to
      the Department of Surgical Oncology at the First Hospital of China Medical
      University. Logistic analysis was performed to identify predictors. The hazard
      risk (HR) of variables obtained from logistic regression was used to construct a
      simple scoring system determined by an aggregate of the points assigned for each
      selected variable. Receiver operator characteristic (ROC) curve was created to
      analyze the specificity. Lymph node metastases were found in 644 (69.1 %) of 932
      patients. After multivariate logistic regression analysis, tumor size, depth of
      invasion, and macroscopic types (P < 0.001) were selected as viable predictors to
      establish the scoring system. ROC curves were plotted to verify the accuracy of
      predicting score and other variables for both Lymph node stage (N stage)
      prediction. It showed that the predicting score system had a better specificity
      and sensitivity (65.71 % and 83.54 %, respectively). The current study suggests
      that a preoperative prediction system to identify the risk of lymph node
      metastasis is feasible. This model may be useful in preoperative counseling about
      the cost and benefit of systemic lymph node dissection.

PMID- 25053601
TI  - Identification of circulating microRNAs as biomarkers in diagnosis of hematologic
      cancers: a meta-analysis.
AB  - Recent studies have provided new insights into the diagnostic value of
      circulating microRNAs (miRNAs) for hematologic cancers. However, inconsistent
      results have been reported on the diagnostic performance of various kinds of
      miRNAs. To systematically assess the potential diagnostic value of miRNAs in
      hematologic cancers, we conducted the present meta-analysis. Multiple databases
      (PubMed, Cochrane Library, EMBASE, CNKI, and Wan Fang) were carefully searched
      for available studies up to April 4, 2014. Sensitivity and specificity were
      pooled using a random-effects model. Likelihood ratio (LR), diagnostic odds ratio
      (DOR), and the area under the curve (AUC) were used to measure the diagnostic
      values. Subgroup and meta-regression analyses were used to find potential sources
      of heterogeneity. Thirty-four studies from 14 publications, which involved 1,159
      hematologic cancer patients and 826 healthy controls, were included in this meta
      analysis. The pooled estimates indicated a moderately high diagnostic accuracy
      for circulating miRNAs, with a sensitivity of 0.83, a specificity of 0.85, a PLR
      of 5.7, a NLR of 0.20, a DOR of 29, and an AUC of 0.91. The subgroup analyses
      showed that diagnostic accuracy was better for acute myeloid leukemia (AML)
      patients and Asians compared with other subgroups. In addition, multiple miRNA
      assays displayed a better performance than single ones. Furthermore, we found
      that plasma might be a more promising matrix for detecting the expression of
      miRNAs than serum. Our results identified the potential use of circulating miRNAs
      in second-line diagnosis for hematologic cancers, especially the value of miRNA
      panels. However, further large cohort studies are still required to confirm our
      findings. 

PMID- 25053602
TI  - Effects of a short messaging service-based skin cancer prevention campaign in
      adolescents.
AB  - BACKGROUND: Skin cancer prevention emphasizes early adoption and practice of sun
      protection behaviors. Adolescence represents a high-risk period for ultraviolet
      radiation exposure, presenting an opportunity for intervention. The ubiquity of
      mobile phones among teens offers an engaging medium through which to communicate
      prevention messages. PURPOSE: To evaluate a skin cancer prevention intervention
      using short messaging service (SMS, or text messages) to impact sun-related
      knowledge, beliefs, and behaviors among adolescents. METHODS: The intervention
      was conducted in middle school youth (N=113) recruited in April or October 2012.
      Participants were English speakers, 11-14 years old, routinely carried a mobile
      phone, and completed a 55-minute sun safety education program. Participants were
      sent three sun safety-themed SMS messages each week for 12 weeks. Skin and sun
      protective knowledge, beliefs, behaviors, and post-intervention program
      satisfaction were collected and analyzed at baseline and end of intervention
      (April/June 2012; October 2012/January 2013). Paired responses were tested for
      equality using Wilcoxon signed-rank tests. RESULTS: Ninety-six students (85%)
      completed the study. At 12 weeks, significant positive changes were reported for
      sun avoidance during peak ultraviolet radiation, sunscreen application, wearing
      hats and sunglasses, and knowledge about skin cancer risk. Participants expressed
      moderately high satisfaction with the program, and 15% shared messages with
      family or friends. CONCLUSIONS: A brief, SMS-based intervention affected youth
      skin cancer prevention behaviors and knowledge. Future research will determine
      whether program effects were sustained at 24 weeks and explore how sun safety
      parenting practices inform these effects.

PMID- 25053603
TI  - [Combination of stereotactic irradiation and chemotherapy or targeted therapies:
      state of the art and preliminary recommendations].
AB  - The clinical management of systemic treatments and irradiation has long been
      studied for conventional irradiation. Yet, many associations are of difficult
      management and some drugs are contra-indicated in the concomitant setting owing
      to excessive toxicities. Sequential regimens using a therapeutic window of
      variable duration (based on drug half-life and tissue wash out) between each
      modality may be preferred for easier logistics and to avoid toxicities. The use
      of intra- and extracranial stereotactic ablative radiation therapy
      (hypofractionated) is expanding rapidly. Yet, little is known regarding
      associations between stereotactic ablative radiation therapy and systemic
      treatments. The short stereotactic ablative radiation therapy course in one day
      to two weeks offers a theoretical advantage compared to longer conventional
      irradiation with respect to shorter discontinuation of therapy. This may be of
      particular interest in situations where cancer is addicted to systemic treatment.
      While it is believed that stereotactic ablative radiation therapy might be safer
      because of limited irradiation volumes and steep gradients sparing most organs at
      risk, it should be noted that irradiation of normal tissues cannot be considered
      null; that stereotactic ablative radiation therapy has vascular effects in
      addition to other cell death radiation-induced mechanisms and cancer progression
      with discontinuation of systemic treatment is often reversible. To date, based on
      several phase II studies, combined stereotactic ablative radiation therapy and
      cetuximab can be recommended in head and neck tumours. Other stereotactic
      ablative radiation therapy-based combinations require prospective phase I-II
      studies and sufficient therapeutic window (in the order of at least 5 half-lives)
      between the systemic and local modalities must be left in routine practice.

PMID- 25053604
TI  - The four most pernicious myths in asbestos litigation: Part I: safe chrysotile
      and idiopathic mesothelioma.
AB  - The now well documented phenomenon of "doubt science" has crept into litigation
      generally, but has had a particularly deleterious effect in asbestos litigation,
      giving rise to pernicious myths that are told and re-told every day in legal
      briefs and in court proceedings. Defendants routinely challenge the admissibility
      of testimony from plaintiffs' expert witnesses when those experts testify about
      certain key concepts in asbestos medicine and asbestos science. Defendants boldly
      proclaim plaintiffs' experts' opinions to be "junk science" and seek to have them
      precluded regardless of how well documented, well researched, well supported and
      well accepted those opinions are. This has become all too routine in asbestos
      litigation, where defendants predictably seek to preclude testimony about medical
      and scientific issues that have been settled for decades and that are not
      legitimately disputed outside of litigation by the unbiased scientific community
      of national and international regulatory agencies and scientific organizations. 

PMID- 25053605
TI  - The four most pernicious myths in asbestos litigation: Part II: safe thresholds
      for exposure and Tyndall lighting as junk science.
AB  - Part I of this survey confronted the first two Most Pernicious Myths in Asbestos
      Litigation: the supposed harmlessness of chrysotile asbestos; and so-called
      idiopathic mesothelioma. Part II discusses the pernicious notions of safe
      exposure thresholds for asbestos and the unreliability of Tyndall lighting.
      Defendants' attempts to preclude plaintiffs' experts from testifying about these
      generally accepted scientific facts are a disservice to the legal system and to
      plaintiffs who have been harmed by asbestos. These defense tactics attempt to
      deny reality and to spin scientific facts in order to keep them from the jurors'
      eyes and ears. This undermines the legal system and harms the integrity of the
      scientific enterprise. Defendants' efforts to manufacture "controversy" over
      previously uncontroversial facts are bald attempts to infect the legal process
      with junk "doubt science." The role of this type of "doubt science" is being
      steadily exposed as legitimate researchers resist the degradation of their
      disciplines and the scientific literature by unprincipled purveyors of this
      insidious brand of junk science. 

PMID- 25053606
TI  - Risks endemic to long-haul trucking in North America: strategies to protect and
      promote driver well-being.
AB  - Long-haul truck drivers in North America function in a work context marked by
      excess physical and psychological workload, erratic schedules, disrupted sleep
      patterns, extreme time pressures, and these factors' far-reaching consequences.
      These work-induced stressors are connected with excess risk for cardiometabolic
      disease, certain cancers, and musculoskeletal and sleep disorders, as well as
      highway crashes, which in turn exert enormous financial burdens on trucking and
      warehousing companies, governments and healthcare systems, along with working
      people within the sector. This article: 1) delineates the unique work environment
      of long-haul truckers, describing their work characteristics and duties; (2)
      discusses the health hazards of long-haul trucking that impact drivers, the
      general population, and trucking enterprises, examining how this work context
      induces, sustains, and exacerbates these hazards; and (3) proposes comprehensive,
      multi-level strategies with potential to protect and promote the health, safety,
      and well-being of truckers, while reducing adverse consequences for companies and
      highway safety. 

PMID- 25053608
TI  - Jonathan Rosen: building a dynamic union-based health and safety program.
AB  - Jonathan Rosen has spent more than 30 years building union-based health and
      safety programs. In the 1970s he was a union activist. In 1980 he became a union
      health and safety committee chair at a Milwaukee manufacturing firm. Following
      that, he had a nearly 20-year career with the New York State Public Employees
      Federation (PEF). He trained as an industrial hygienist and developed a highly
      regarded public sector union-based health and safety program. PEF's Health and
      Safety Department supported a network of union health and safety committees.
      Program accomplishments included innovative work on workplace violence
      prevention, indoor environmental quality, infectious diseases, and ergonomics.
      Mr. Rosen promoted collaboration among unions, helped support new activists,
      advocated tirelessly for injured workers, and formed an effective alliance with
      researchers. Rosen discusses essential strategies for mobilizing union members
      and gaining commitment to health and safety from unions, employers, and policy
      makers. 

PMID- 25053607
TI  - Occupational safety and health education and training for underserved
      populations.
AB  - This article presents an analysis of the essential elements of effective
      occupational safety and health education and training programs targeting
      underserved communities. While not an exhaustive review of the literature on
      occupational safety and health training, the paper provides a guide for
      practitioners and researchers to the key factors they should consider in the
      design and implementation of training programs for underserved communities. It
      also addresses issues of evaluation of such programs, with specific emphasis on
      considerations for programs involving low-literacy and limited-English-speaking
      workers. 

PMID- 25053610
TI  - Digestive system dysfunction in cystic fibrosis: challenges for nutrition
      therapy.
AB  - Cystic fibrosis can affect food digestion and nutrient absorption. The underlying
      mutation of the cystic fibrosis trans-membrane regulator gene depletes functional
      cystic fibrosis trans-membrane regulator on the surface of epithelial cells
      lining the digestive tract and associated organs, where Cl(-) secretion and
      subsequently secretion of water and other ions are impaired. This alters pH and
      dehydrates secretions that precipitate and obstruct the lumen, causing
      inflammation and the eventual degradation of the pancreas, liver, gallbladder and
      intestine. Associated conditions include exocrine pancreatic insufficiency,
      impaired bicarbonate and bile acid secretion and aberrant mucus formation,
      commonly leading to maldigestion and malabsorption, particularly of fat and fat
      soluble vitamins. Pancreatic enzyme replacement therapy is used to address this
      insufficiency. The susceptibility of pancreatic lipase to acidic and enzymatic
      inactivation and decreased bile availability often impedes its efficacy. Brush
      border digestive enzyme activity and intestinal uptake of certain disaccharides
      and amino acids await clarification. Other complications that may contribute to
      maldigestion/malabsorption include small intestine bacterial overgrowth, enteric
      circular muscle dysfunction, abnormal intestinal mucus, and intestinal
      inflammation. However, there is some evidence that gastric digestive enzymes,
      colonic microflora, correction of fatty acid abnormalities using dietary n-3
      polyunsaturated fatty acid supplementation and emerging intestinal biomarkers can
      complement nutrition management in cystic fibrosis. 

PMID- 25053611
TI  - Statistical analysis with dilatation for development process of human fetuses.
AB  - This paper is concerned with the development process of human fetuses. Though the
      development process of human fetuses still includes many unknown issues, it is
      known that a certain harmonious relationship between the organs can be observed.
      This knowledge is based on our intuition, but we have no theory which clarifies
      these harmonized developments. The paper aims to give a mathematical
      understanding of the notion of harmonized development through the use of
      dilatation, which is a measure of the departure from conformal mapping. The
      asymptotics for dilatation have been developed using certain efficient models of
      quasiconformal mapping. The proposed method of dilatation is effectively applied
      to the human fetus data.

PMID- 25053612
TI  - Foreword.

PMID- 25053614
TI  - What is the cost of a healthy diet? Using diet data from the UK Women's Cohort
      Study.
AB  - BACKGROUND: A healthy diet is important to promote health and well-being while
      preventing chronic disease. However, the monetary cost of consuming such a diet
      can be a perceived barrier. This study will investigate the cost of consuming a
      range of dietary patterns. METHODS: A cross-sectional analysis, where cost of
      diet was assigned to dietary intakes recorded using a Food Frequency
      Questionnaire. A mean daily diet cost was calculated for seven data-driven
      dietary patterns. These dietary patterns were given a healthiness score according
      to how well they comply with the UK Department of Health's Eatwell Plate
      guidelines. This study involved ~35 000 women recruited in the 1990s into the UK
      Women's Cohort Study. RESULTS: A significant positive association was observed
      between diet cost and healthiness of the diet (p for trend >0.001). The
      healthiest dietary pattern was double the price of the least healthy, L6.63/day
      and L3.29/day, respectively. Dietary diversity, described by the patterns, was
      also shown to be associated with increased cost. Those with higher education and
      a professional or managerial occupation were more likely to consume a healthier
      diet. CONCLUSIONS: A healthy diet is more expensive to the consumer than a less
      healthy one. In order to promote health through diet and reduce potential
      inequalities in health, it seems sensible that healthier food choices should be
      made more accessible to all.

PMID- 25053615
TI  - Employment status and mental health among persons with and without a disability:
      evidence from an Australian cohort study.
AB  - BACKGROUND: Unemployment and economic inactivity are associated with worse mental
      health in the general population, but there is limited understanding of whether
      these relationships are different for those persons with mental or physical
      disabilities. The aim of this study was to assess whether there were differences
      in mental health by labour force status among persons with and without
      disabilities. METHOD: Over eight annual waves of the Household, Income and Labour
      Dynamics in Australia (HILDA) survey, a total of 2379 people with disabilities
      and 11 417 people without disabilities were identified. Mental health using the
      Mental Component Summary (MCS) from the Short Form 36 was modelled as a function
      of labour force status using fixed-effects regression models to control for time
      invariant confounding. Differences between those with and without disabilities
      were assessed by including an interaction term in regression models. RESULTS:
      After finding evidence of effect modification, regression models were stratified
      by disability status. After adjustment, unemployment and economic inactivity were
      associated with a -1.85 (95% CI -2.96 to -0.73, p=0.001) and -2.66 (95% CI -3.46
      to -1.86, p<0.001) reduction in scores of the MCS among those with a disability.
      For those without a disability, there were smaller declines associated with
      unemployment (-0.57, 95% CI -1.02 to -0.12, p=0.013) and economic inactivity (
      0.34, 95% CI -0.64 to 0.05, p=0.022). CONCLUSIONS: These results suggest a
      greater reduction in mental health for those persons with disabilities who were
      unemployed or economically inactive than those who were employed. This highlights
      the value of employment for people with disabilities.

PMID- 25053616
TI  - The effect of urban green on small-area (healthy) life expectancy.
AB  - BACKGROUND: Several epidemiological studies have investigated the effect of the
      quantity of green space on health outcomes such as self-rated health, morbidity
      and mortality ratios. These studies have consistently found positive associations
      between the quantity of green and health. However, the impact of other aspects,
      such as the perceived quality and average distance to public green, and the
      effect of urban green on population health are still largely unknown. METHODS:
      Linear regression models were used to investigate the impact of three different
      measures of urban green on small-area life expectancy (LE) and healthy life
      expectancy (HLE) in The Netherlands. All regressions corrected for average
      neighbourhood household income, accommodated spatial autocorrelation, and took
      measurement uncertainty of LE, HLE as well as the quality of urban green into
      account. RESULTS: Both the quantity and the perceived quality of urban green are
      modestly related to small-area LE and HLE: an increase of 1 SD in the percentage
      of urban green space is associated with a 0.1-year higher LE, and, in the case of
      quality of green, with an approximately 0.3-year higher LE and HLE. The average
      distance to the nearest public green is unrelated to population health.
      CONCLUSIONS: The quantity and particularly quality of urban green are positively
      associated with small-area LE and HLE. This concurs with a growing body of
      evidence that urban green reduces stress, stimulates physical activity, improves
      the microclimate and reduces ambient air pollution. Accordingly, urban green
      development deserves a more prominent place in urban regeneration and
      neighbourhood renewal programmes.

PMID- 25053617
TI  - The chemokine CXC4 and CC2 receptors form homo- and heterooligomers that can
      engage their signaling G-protein effectors and betaarrestin.
AB  - G-protein-coupled receptors have been shown to assemble at least as dimers early
      in the biosynthetic path, but some evidence suggests that they can also form
      larger oligomeric complexes. Using the human chemokine receptors CXCR4 and CCR2
      as models, we directly probed the existence of higher order homo- and
      heterooligomers in human embryonic kidney cells. Combining bimolecular
      fluorescence and luminescence complementation (BiFC, BiLC) with bioluminescence
      resonance energy transfer (BRET) assays, we show that CXCR4 and CCR2 can assemble
      as homo- and heterooligomers, forming at least tetramers. Selective activation of
      CCR2 with the human monocyte chemotactic protein 1 (MCP-1) resulted in trans
      conformational rearrangement of the CXCR4 dimer with an EC50 of 19.9 nM,
      compatible with a CCR2 action. Moreover, MCP-1 promoted the engagement of
      Galphai1, Galpha13, Galphaz, and betaarrestin2 to the heterooligomer, resulting
      in calcium signaling that was synergistically potentiated on coactivation of CCR2
      and CXCR4, demonstrating that complexes larger than dimers reach the cell surface
      as functional units. A mutation of CXCR4 (N119K), which prevents Gi activation,
      also affects the CCR2-promoted engagement of Galphai1 and betaarrestin2 by the
      heterooligomer, supporting the occurrence of transprotomer regulation. Together,
      the results demonstrate that homo- and heteromultimeric CXCR4 and CCR2 can form
      functional signaling complexes that have unique properties.

PMID- 25053618
TI  - Biosynthesis of drug metabolites and quantitation using NMR spectroscopy for use
      in pharmacologic and drug metabolism studies.
AB  - The contribution of drug metabolites to the pharmacologic and toxicologic
      activity of a drug can be important; however, for a variety of reasons
      metabolites can frequently be difficult to synthesize. To meet the need of having
      samples of drug metabolites for further study, we have developed biosynthetic
      methods coupled with quantitative NMR spectroscopy (qNMR) to generate solutions
      of metabolites of known structure and concentration. These quantitative samples
      can be used in a variety of ways when a synthetic sample is unavailable,
      including pharmacologic assays, standards for in vitro work to help establish
      clearance pathways, and/or as analytical standards for bioanalytical work to
      ascertain exposure, among others. We illustrate five examples of metabolite
      biosynthesis and qNMR. The types of metabolites include one glucuronide and four
      oxidative products. Concentrations of the isolated metabolite stock solutions
      ranged from 0.048 to 8.3 mM, with volumes from approximately 0.04 to 0.150 ml in
      hexadeutarated dimethylsulfoxide. These specific quantified isolates were used as
      standards in the drug discovery setting as substrates in pharmacology assays, for
      bioanalytical assays to establish exposure, and in variety of routine absorption,
      distribution, metabolism, and excretion assays, such as protein binding and
      determining blood-to-plasma ratios. The methods used to generate these materials
      are described in detail with the objective that these methods can be generally
      used for metabolite biosynthesis and isolation. 

PMID- 25053619
TI  - Brain penetration of WEB 2086 (Apafant) and dantrolene in Mdr1a (P-glycoprotein)
      and Bcrp knockout rats.
AB  - Transporter gene knockout rat models are attracting increasing interest for
      mechanistic studies of new drugs as transporter substrates or inhibitors in vivo.
      However, limited data are available on the functional validity of such models at
      the blood-brain barrier. Therefore, the present study evaluated Mdr1a [P
      glycoprotein (P-gp)], Bcrp, and combined Mdr1a/Bcrp knockout rat strains for the
      influence of P-gp and breast cancer resistance protein (BCRP) transport proteins
      on brain penetration of the selective test substrates [(14)C]WEB 2086 (3-[4-(2
      chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo-[4,3-a][1,4]-diazepin-2
      yl]-1-(4-morpholinyl)-1-propanon) for P-gp and dantrolene for BCRP. Brain-to
      plasma concentration ratios (BPR) were measured after intravenous coinfusions of
      5.5 umol/kg per hour [(14)C]WEB 2086 and 2 umol/kg per hour dantrolene for 2
      hours in groups of knockout or wild-type rats. Compared with wild-type controls,
      mean BPR of [(14)C]WEB 2086 increased 8-fold in Mdr1a knockouts, 9.5-fold in
      double Mdr1a/Bcrp knockouts, and 7.3-fold in zosuquidar-treated wild-type rats,
      but was unchanged in Bcrp knockout rats. Mean BPR of dantrolene increased 3.3
      fold in Bcrp knockouts and 3.9-fold in double Mdr1a/Bcrp knockouts compared with
      wild type, but was unchanged in the Mdr1a knockouts. The human intestinal CaCo-2
      cell bidirectional transport system in vitro confirmed the in vivo finding that
      [(14)C]WEB 2086 is a substrate of P-gp but not of BCRP. Therefore, Mdr1a, Bcrp,
      and combined Mdr1a/Bcrp knockout rats provide functional absence of these efflux
      transporters at the blood-brain barrier and are a suitable model for mechanistic
      studies on the brain penetration of drug candidates. 

PMID- 25053620
TI  - Metabolism of diosbulbin B in vitro and in vivo in rats: formation of reactive
      metabolites and human enzymes involved.
AB  - Diosbulbin B (DB), a major constituent of the furano-norditerpenes in Dioscorea
      bulbifera Linn, exhibits potential antineoplasmic activity and hepatotoxicity.
      The metabolism and reactive metabolites of DB in vitro (with human and animal
      liver microsomes) and in vivo in rats were investigated. The human enzymes
      involved in DB metabolism were identified. DB was first catalyzed into reactive
      metabolites of 2-butene-1,4-dial derivatives dependent on NADPH and then trapped
      by Tris base or oxidized to hemiacetal lactones (M12 and M13) in microsomal
      incubations. Tris base was used as buffer constituent and as a trapping agent for
      aldehyde. Methoxylamine and glutathione (GSH) were also used as trapping agents.
      DB metabolism in vivo in rats after oral administration was consistent with that
      in vitro. The structures of M12 and M13, as well as mono-GSH conjugates of DB
      (M31), were confirmed by nuclear magnetic resonance spectroscopy of the
      chemically synthesized products. The bioactivation enzymes of DB were identified
      as CYP3A4/5, 2C9, and 2C19. CYP3A4 was found to be the primary enzyme using human
      recombinant cytochrome P450 enzymes, specific inhibitory studies, and a relative
      activity factor approach for pooled human liver microsomes. Michaelis-Menten
      constants K(m) and V(max) were determined by the formation of M31. The reactive
      metabolites may be related to the hepatotoxicity of DB. The gender difference in
      CYP3A expression in mice and rats contributed to the gender-related liver injury
      and pharmacokinetics in mice and rats, respectively.

PMID- 25053621
TI  - Simulator-based assessment of haptic surgical skill: a comparative study.
AB  - The aim of this study was to examine if the forces applied by users of a haptic
      simulator could be used to distinguish expert surgeons from novices. Seven
      surgeons with significant operating room expertise and 9 novices with no surgical
      experience participated in this study. The experimental task comprised exploring
      4 virtual materials with the haptic device and learning the precise forces
      required to compress the materials to various depths. The virtual materials
      differed in their stiffness and force-displacement profiles. The results revealed
      that for nonlinear virtual materials, surgeons applied significantly greater
      magnitudes of force than novices. Furthermore, for the softer nonlinear and
      linear materials, surgeons were significantly more accurate in reproducing forces
      than novices. The results of this study suggest that the magnitudes of force
      measured using haptic simulators may be used to objectively differentiate
      experts' haptic skill from that of novices. This knowledge can inform the design
      of virtual reality surgical simulators and lead to the future incorporation of
      haptic skills training in medical school curricula. 

PMID- 25053622
TI  - Vitamin D receptor polymorphism FokI and cancer risk: a comprehensive meta
      analysis.
AB  - Numerous studies investigated the associations of VDR polymorphisms with various
      types of cancer, suggesting an influence on cancer risk. FokI is one of the most
      frequently analysed polymorphisms but the results from single studies are
      contradictory. We performed a meta-analysis looking at the association between
      the FokI and all cancer sites and investigating sources of heterogeneity. We
      identified 77 independent studies up to April 2014. We presented the summary odds
      ratios (SORs) by cancer sites, ethnicity and study features. We found a
      significant association between FokI and ovarian cancer for ff genotype versus FF
      with no heterogeneity: SOR = 1.20 (95% CI: 1.02-1.41, I (2) = 0%). Moreover, we
      found a significant increased risk of any cancer: SOR = 1.08 (95% CI: 1.01-1.16,
      I (2) = 58%). A significant increased risk of any cancer is confirmed among
      Caucasian, among studies in Hardy-Weinberg equilibrium and nested case-control
      studies. Furthermore, among studies in Hardy-Weinberg equilibrium, skin cancer
      was found significantly associated with FokI: SOR = 1.24 (95% CI: 1.01-1.54; I
      (2) = 24%) for ff versus FF. The estimated number of cases attributable to ff
      genotype is 4221 for ovarian cancer and 52858 for skin cancer worldwide each
      year. No indication for publication bias was found for any cancer site. In
      conclusion, we found an overall significant association of FokI polymorphism with
      any cancer, with differential effect by ethnicity. In particular, the summary
      estimates indicate an increase risk for ovarian and skin cancer for ff versus FF.
      However, other factors may act modifying the association, and further studies are
      needed to clarify the impact on cancer risk. 

PMID- 25053624
TI  - Consumption of a high-fat diet abrogates inhibitory effects of methylseleninic
      acid on spontaneous metastasis of Lewis lung carcinoma in mice.
AB  - We investigated the effect of dietary supplementation with selenium on
      spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet. Mice
      were fed a low-fat diet or that diet modified with 45% of calories from corn oil
      and supplemented with 0 or 2.5mg selenium/4029 kcal as methylseleninic acid.
      After 6 weeks, mice were each injected 2.5 * 10(5) Lewis lung carcinoma cells
      subcutaneously. The resulting primary tumor was removed surgically 10 days later;
      the experiment was terminated after an additional 10 days. High-fat feeding
      increased pulmonary metastases by 17% compared to the low-fat diet (P < 0.01).
      Selenium supplementation reduced the metastases by 11% compared to
      nonsupplemented controls (P < 0.05); the reduction was less for animals fed the
      high-fat diet (5%) than for those fed the low-fat diet (18%). Supplemental Se
      lowered plasma concentrations of proteases (urokinase plasminogen activator, P <
      0.01; matrix metalloproteinase-9, P < 0.05) and angiogenic factors (vascular
      endothelial growth factor, P < 0.01; tissue inhibitor of metalloproteinase-1, P <
      0.01) compared to nonsupplemented controls. High-fat feeding increased plasma
      concentrations of adipokines plasminogen activator inhibitor-1, monocyte
      chemotactic protein-1, tumor necrosis factor-alpha, and leptin regardless of the
      level of dietary selenium; supplemental selenium lowered plasma concentrations of
      plasminogen activator inhibitor-1 (P <= 0.05) and monocyte chemotactic protein-1
      (P <= 0.05) in low-fat fed mice but not in high-fat fed mice. These results
      indicate that consumption of a high-fat diet abrogated the antimetastatic effects
      of selenium by increasing the expression of adipose-derived inflammatory
      cytokines. 

PMID- 25053625
TI  - The effect of knockout of sulfotransferases 1a1 and 1d1 and of transgenic human
      sulfotransferases 1A1/1A2 on the formation of DNA adducts from furfuryl alcohol
      in mouse models.
AB  - Furfuryl alcohol is a rodent carcinogen present in numerous foodstuffs.
      Sulfotransferases (SULTs) convert furfuryl alcohol into the DNA reactive and
      mutagenic 2-sulfoxymethylfuran. Sensitive techniques for the isotope-dilution
      ultra performance liquid chromatography-tandem mass spectrometry quantification
      of resulting DNA adducts, e.g. N (2)-((furan-2-yl)methyl)-2'-deoxyguanosine (N
      (2)-MF-dG), were developed. To better understand the contribution of specific
      SULT forms to the genotoxicity of furfuryl alcohol in vivo, we studied the tissue
      distribution of N (2)-MF-dG in different mouse models. Earlier mutagenicity
      studies with Salmonella typhimurium strains expressing different human and murine
      SULT forms indicated that human SULT1A1 and murine Sult1a1 and 1d1 catalyze
      furfuryl alcohol sulfo conjugation most effectively. Here, we used three mouse
      lines to study the bioactivation of furfuryl alcohol by murine SULTs, FVB/N wild
      type (wt) mice and two genetically modified models lacking either murine Sult1a1
      or Sult1d1. The animals received a single dose of furfuryl alcohol, and the
      levels of the DNA adducts were determined in liver, kidney, lung, colon and small
      intestine. The effect of Sult1d1 gene disruption on the genotoxicity of furfuryl
      alcohol was moderate and limited to kidney and small intestine. In contrast, the
      absence of functional Sult1a1 had a massive influence on the adduct levels, which
      were lowered by 33-73% in all tissues of the female Sult1a1 null mice compared
      with the wt animals. The detection of high N (2)-MF-dG levels in a humanized
      mouse line expressing hSULT1A1/1A2 instead of endogeneous Sult1a1 and Sult1d1
      supports the hypothesis that furfuryl alcohol is converted to the mutagenic 2
      sulfoxymethylfuran also in humans. 

PMID- 25053626
TI  - Dihydromethysticin from kava blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone-induced lung tumorigenesis and differentially reduces DNA
      damage in A/J mice.
AB  - We have previously shown that kava and its flavokavain-free Fraction B completely
      blocked 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung
      tumorigenesis in A/J mice with a preferential reduction in NNK-induced O (6)
      methylguanine (O (6)-mG). In this study, we first identified natural (+)
      dihydromethysticin (DHM) as a lead compound through evaluating the in vivo
      efficacy of five major compounds in Fraction B on reducing O (6)-mG in lung
      tissues. (+)-DHM demonstrated outstanding chemopreventive activity against NNK
      induced lung tumorigenesis in A/J mice with 97% reduction of adenoma multiplicity
      at a dose of 0.05mg/g of diet (50 ppm). Synthetic (+/-)-DHM was equally effective
      as the natural (+)-DHM in these bioassays while a structurally similar analog,
      (+)-dihydrokavain (DHK), was completely inactive, revealing a sharp in vivo
      structure-activity relationship. Analyses of an expanded panel of NNK-induced DNA
      adducts revealed that DHM reduced a subset of DNA adducts in lung tissues derived
      from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the active metabolite
      of NNK). Preliminary 17-week safety studies of DHM in A/J mice at a dose of
      0.5mg/g of diet (at least 10* its minimum effective dose) revealed no adverse
      effects, suggesting that DHM is likely free of kava's hepatotoxic risk. These
      results demonstrate the outstanding efficacy and promising safety margin of DHM
      in preventing NNK-induced lung tumorigenesis in A/J mice, with a unique mechanism
      of action and high target specificity. 

PMID- 25053629
TI  - The perception of allergen-specific immunotherapy among chest physicians: an
      Italian survey.
AB  - BACKGROUND: This questionnaire-based study evaluated the overall level of
      knowledge about allergen-specific immunotherapy (SIT) among chest physicians, who
      are frequently involved in the management of respiratory allergies. This
      represents an interesting aspect, because chest physicians intercept many of the
      patients with allergic rhinitis w/wo asthma, in which SIT could be potentially
      indicated. METHODS: A panel of experts prepared a questionnaire, involving 16
      main points of interest/questions concerning the knowledge and use of SIT.
      Questionnaires were e-mailed (September-October, 2011) to randomly-selected
      specialists, and were returned anonymously. RESULTS: 81 questionnaires from
      specialists using SIT were eligible. The respondent population had a mean age of
      51 years (range 33-63 years, 74% male). The general knowledge on SIT is overall
      satisfactory among pulmonologists, and they are well aware that SIT is
      recommended in the available guidelines. Nevertheless, about 50% of physicians
      still believe that SIT has to be used as a last-choice adjunct when
      pharmacotherapy fails. Chest physicians are well aware that SIT has a disease
      modifying effect, in addition to its short-term clinical efficacy. Finally, the
      majority of interviewed specialists agree on the need of getting more information
      and education on SIT. CONCLUSIONS: This survey about the perception of SIT among
      chest physicians in Italy highlighted a satisfactory overall knowledge of SIT and
      only few weak points. These results would allow to take appropriate educational
      actions and this questionnaire could be used to monitor the possible effects of
      divulgation and educational initiatives over time.

PMID- 25053628
TI  - Draft sequencing and analysis of the genome of pufferfish Takifugu flavidus.
AB  - The pufferfish Takifugu flavidus is an important economic species due to its
      outstanding flavour and high market value. It has been regarded as an excellent
      model of genetic study for decades as well. In the present study, three mate-pair
      libraries of T. flavidus genome were sequenced by the SOLiD 4 next-generation
      sequencing platform, and the draft genome was constructed with the short reads
      using an assisted assembly strategy. The draft consists of 50,947 scaffolds with
      an N50 value of 305.7 kb, and the average GC content was 45.2%. The combined
      length of repetitive sequences was 26.5 Mb, which accounted for 6.87% of the
      genome, indicating that the compactness of T. flavidus genome was approximative
      with that of T. rubripes genome. A total of 1,253 non-coding RNA genes and 30,285
      protein-encoding genes were assigned to the genome. There were 132,775 and 394
      presumptive genes playing roles in the colour pattern variation, the relatively
      slow growth and the lipid metabolism, respectively. Among them, genes involved in
      the microtubule-dependent transport system, angiogenesis, decapentaplegic pathway
      and lipid mobilization were significantly expanded in the T. flavidus genome.
      This draft genome provides a valuable resource for understanding and improving
      both fundamental and applied research with pufferfish in the future. 

PMID- 25053627
TI  - Assay of lapatinib in murine models of cigarette smoke carcinogenesis.
AB  - Lapatinib, a dual tyrosine kinase inhibitor targeting the epidermal growth factor
      receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), is
      prescribed for the treatment of patients with metastatic breast cancer
      overexpressing HER-2. Involvement of this drug in pulmonary carcinogenesis has
      been poorly investigated. We used murine models suitable to evaluate cigarette
      smoke-related molecular and histopathological alterations. A total of 481 Swiss H
      mice were used. The mice were exposed to mainstream cigarette smoke (MCS) during
      the first four months of life. After 10 weeks, MCS caused an elevation of bulky
      DNA adducts, oxidative DNA damage and an extensive downregulation of microRNAs in
      lung. After four months, an increase in micronucleus frequency was observed in
      peripheral blood erythrocytes. After 7.5 months, histopathological alterations
      were detected in the lung, also including benign tumors and malignant tumors, and
      in the urinary tract. A subchronic toxicity study assessed the non-toxic doses of
      lapatinib, administered daily with the diet after weaning. After 10 weeks,
      lapatinib significantly attenuated the MCS-related nucleotide changes and
      upregulated several low-intensity microRNAs in lung. The drug poorly affected the
      MCS systemic genotoxicity and had modest protective effects on MCS-induced
      preneoplastic lesions in lung and kidney, when administered under conditions that
      temporarily mimicked interventions either in current smokers or ex-smokers. On
      the other hand, it caused some toxicity to the liver. Thus, on the whole,
      lapatinib appears to have a low impact in the smoke-related lung carcinogenesis
      models used, especially in terms of tumorigenic response. 

PMID- 25053630
TI  - Tetranychus urticae allergy in a population without occupational exposure.
AB  - BACKGROUND: Tetranychus urticae is a phytophagus mite found in the leaves of
      numerous plants. High sensitization rates have been demonstrated, however,
      provocation tests have only been performed in an occupational setting. OBJECTIVE:
      To assess accuracy of skin prick tests and clinical relevance of T. urticae
      sensitization by means of conjunctival provocation tests (CPT) in a population
      without occupational exposure and to evaluate possible environmental risk factors
      for T. urticae allergy. METHODS: Patients >= 18 years old sensitized to T.
      urticae (n = 12) and a non-sensitized control group (n = 12) were invited to
      perform CPT with T. urticae and fulfill a questionnaire including demographic
      data, questions on environmental exposure to T. urticae and allergy
      symptoms/diagnosis. A single-blinded placebo-controlled CPT with T. urticae
      (Leti(r)) was performed with increasing concentrations (0.002, 0.02, 0.2 and 2
      mg/mL) and considered positive if conjunctival hyperemia, palpebral edema or
      lacrimation were observed in the tested eye. RESULTS: Of T. urticae sensitized
      patients (mean wheal 4.4 +/- 1.5 mm), 9 had a positive CPT, including 3
      monosensitized. A good diagnostic accuracy was found for skin prick tests: AUC =
      0.952, sensitivity = 100%, specificity = 80%, positive likelihood ratio = 5 and
      negative likelihood ratio = 0 for a 3 mm wheal. No differences were found between
      allergic and non-allergic subjects regarding atopy, allergic disease or farming
      activities. CONCLUSIONS: A high prevalence of allergy to Tetranychus urticae was
      found in the north of Portugal. Future studies with a larger number of patients
      are needed to evaluate its relation to clinical symptoms and the impact of
      environmental factors.

PMID- 25053631
TI  - In patients with LTP syndrome food-specific IgE show a predictable hierarchical
      order.
AB  - BACKGROUND: Lipid transfer protein (LTP) is a widely cross-reacting allergen in
      plant foods. OBJECTIVE: To assess whether IgE to vegetable foods show predictable
      trends in LTP allergic patients. METHODS: Clinical allergy to plant foods other
      than peach was sought in 15 consecutive peach-allergic adults monosensitized to
      LTP. IgE specific for peach, apple, hazelnut, walnut, peanut, lentil, maize,
      soybean, tomato, sesame, mustard melon, kiwi, and celery as well as to mugwort
      pollen was measured. RESULTS: Peach-specific IgE levels exceeded IgE to all other
      study foods. The higher were peach-specific IgE levels, the higher was the
      probability that other plant-derived foods scored positive. Mean IgE levels
      specific for all study foods were strongly correlated to peach specific IgE. Food
      specific IgE followed a rather precise hierarchy, both in terms of number of
      positive in-vitro tests and of IgE levels, with apple at the second place after
      peach, followed by walnut, hazelnut, peanut, lentil, maize, soybean, tomato,
      kiwi, sesame, mustard, melon, and celery. Such hierarchy was not necessarily
      paralleled by clinical allergy as lentil, maize, and soybean scored positive in
      the majority of patients, but induced allergy in 0, 1, and 0 patients,
      respectively. IgE levels were not necessarily correlated with the severity of
      clinical allergy. Little or no IgE reactivity to mugwort pollen was found.
      CONCLUSIONS: In LTP syndrome, IgE reactivity to foods other than peach is in most
      cases predictable and follows a regular sequence that probably depends on the
      degree of homology with Pru p3. The reasons why some foods are tolerated by most
      patients despite elevated IgE reactivity remains to be elucidated.

PMID- 25053632
TI  - Middle lobe syndrome: a rare presentation of allergic bronchopulmonary
      aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a disease predominantly seen in
      susceptible asthmatic subjects, due to a hypersensitivity phenomenon caused by
      colonisation of the airways by Aspergillus species. Although collapse, both lobar
      and segmental due to mucoid impaction, is not uncommon in ABPA, a middle lobe
      syndrome (MLS) secondary to ABPA is rather an uncommon association. We report
      this rare and unusual clinical presentation in a 36-year-old male, who presented
      for evaluation of a "non resolving pneumonia". Imaging suggested the presence of
      a MLS and central bronchiectasis. Further investigations revealed that the
      patient met 6/8 of the essential diagnostic criteria for ABPA. Appropriate
      therapy with oral corticosteroids resulted in remarkable symptomatic improvement.

PMID- 25053633
TI  - Prurigo simplex subacuta or prurigo simplex acuta?
AB  - Prurigo is a condition of nodular cutaneous lesions that itch intensely. Prurigo
      lesions are divided into acute, subacute and chronic forms that itch intensely.
      Subacute prurigo (SP) clinically presents as excoriated papules mostly in a
      symmetrical distribution on the extensor surfaces of the extremities, neck, lower
      trunk, and buttocks. It tends to occur in middle-aged patients, especially in
      women. Herein, we described prurigo simplex subacuta in a 4-year-old boy. It was
      histopathologically documented. 

PMID- 25053634
TI  - Diagnosis of eosinophilic esophagitis in an infant undergoing milk oral
      immunotherapy - a case report.
AB  - Although the standard of care for cow's milk (CM) allergy is strict food
      avoidance, oral immunotherapy (OIT) is being widely investigated as an
      alternative management option in certain cases. Immediate adverse reactions to
      OIT have been described, but its long-term effects are much less often reported.
      We present the case of a girl diagnosed with IgE-mediated CM allergy that was
      proposed for our CM OIT protocol at the age of 3 years. The first sessions (dose
      escalation up to 5 ml) were well tolerated, however eight hours after her daily
      morning dose of 5 ml CM the child developed late episodes of vomiting. No other
      symptoms, particularly immediately after CM ingestion, were reported. These
      episodes became progressively worse and on the third day she presented mild
      dehydration and blood eosinophilia. After OIT interruption, a progressive
      clinical improvement was observed. An esophageal endoscopy was performed, showing
      signs of eosinophilic esophagitis (EoE) with peak 20 eosinophils/hpf. After
      treatment with topical swallowed fluticasone (500 mcg bid) and a CM-free diet for
      4 months, the child was asymptomatic and endoscopy and biopsy findings were
      normal.The long-term effects of milk OIT are still in part unknown. We
      hypothesize that eosinophilic esophagitis may have been a consequence of OIT in
      this case. The findings seem to indicate that food allergy may play a role in the
      pathogenesis of esophageal eosinophilia and stress the importance of a well
      programmed long-term follow-up of patients that have undergone milk OIT.

PMID- 25053635
TI  - An unusual complication of late onset allergic contact dermatitis to povidone
      iodine in oral & maxillofacial surgery - a report of 2 cases.
AB  - BACKGROUND: Povidone iodine (PVP-I) is a chemical complex of polyvinylpyrrolidone
      (also known as povidone or PVP) and elemental iodine. Iodine containing compounds
      are widely and commonly used as antiseptics and disinfectants. They are available
      in various forms like aqueous solution, tincture, aerosol, ointment, or foam.
      Skin irritation to them is due to the oxidative effects of iodine. Because of the
      low free iodine concentration in povidone-iodine, skin irritation is less
      frequent from short contact (1). CASE: We report two cases, both with no history
      of allergy to any drugs, who developed an allergic reaction 24 hours after the
      usage of povidone iodine as a pre-operative antiseptic to prepare (scrub) the
      lower third of face before surgical removal of third molars. This case report was
      granted an exemption by the ethical committee of our institution review board.
      The Helsinki declaration doesn't apply to this case presentation. CONCLUSIONS:
      PVP-1 is the most commonly used antiseptic scrubbing solution prior to most
      surgeries. However, allergic contact dermatitis due to PVP-I has not been
      extensively documented or reported and hence under evaluated, compared to other
      commonly encountered allergens. There is almost general agreement to the
      proposition that PVP-I is a very rare sensitizer (2,3) though there are some
      conflicting reports on the matter. However, sometimes when prolonged skin contact
      with PVP-I occurs when used as a pre-operative antiseptic agent, it can cause
      allergic dermatitis (4,5). Does this finding make pre-operative testing for
      allergies to PVP-1 necessary in all patients? A point to ponder.

PMID- 25053636
TI  - Timely immunisation of premature infants against rotavirus in the neonatal
      intensive care unit.

PMID- 25053637
TI  - Abnormal sensory reactivity in preterm infants during the first year correlates
      with adverse neurodevelopmental outcomes at 2 years of age.
AB  - BACKGROUND: Sensory experience is the basis for learning in infancy. In older
      children, abnormal sensory reactivity is associated with behavioural and
      developmental disorders. We hypothesised that in preterm infants, abnormal
      sensory reactivity during infancy would be associated with perinatal
      characteristics and correlate with 2-year neurodevelopmental outcomes. METHODS:
      We conducted a prospective observational study of infants with birth weight
      <=1500 g using the Test of Sensory Function in Infants (TSFI) in the first year.
      Infants with gestational age <=30 weeks were tested with the Bayley Scales of
      Infant and Toddler Development III (BSID III) at 24 months. RESULTS: Of the 72
      participants evaluated at 4-12 months corrected age (median 8 months), 59 (82%)
      had a least one TSFI score concerning for abnormal sensory reactivity. Lower
      gestational age was associated with abnormal reactivity to deep pressure and
      vestibular stimulation (p<0.001). Poor ocular-motor control predicted worse
      cognitive and motor scores in early childhood (OR 16.7; p=0.004), but was tightly
      correlated to the presence of severe white matter injury. Poor adaptive motor
      function in response to tactile stimuli predicted worse BSID III motor (p=0.01)
      and language scores (p=0.04) at 2 years, even after adjusting for confounders.
      CONCLUSIONS: Abnormal sensory reactivity is common in preterm infants; is
      associated with immaturity at birth, severe white matter injury and lower primary
      caregiver education; and predicts neurodevelopmental delays. Early identification
      of abnormal sensory reactivity of very preterm infants may promote parental
      support and education and may facilitate improved neurodevelopment.

PMID- 25053639
TI  - Emerging regulators of vascular smooth muscle cell function in the development
      and progression of atherosclerosis.
AB  - After a period of relative senescence in the field of vascular smooth muscle cell
      (VSMC) research with particular regards to atherosclerosis, the last few years
      has witnessed a resurgence, with extensive research re-assessing potential
      molecular mechanisms and pathways that modulate VSMC behaviour within the
      atherosclerotic-prone vessel wall and the atherosclerotic plaque itself.
      Attention has focussed on the pathological contribution of VSMC in plaque
      calcification; systemic and local mediators such as inflammatory molecules and
      lipoproteins; autocrine and paracrine regulators which affect cell-cell and cell
      to matrix contacts alongside cytoskeletal changes. In this brief focused review,
      recent insights that have been gained into how a myriad of recently identified
      factors can influence the pathological behaviour of VSMC and their subsequent
      contribution to atherosclerotic plaque development and progression has been
      discussed. An overriding theme is the mechanisms involved in the alterations of
      VSMC function during atherosclerosis. 

PMID- 25053638
TI  - SCN10A/Nav1.8 modulation of peak and late sodium currents in patients with early
      onset atrial fibrillation.
AB  - AIMS: To test the hypothesis that vulnerability to atrial fibrillation (AF) is
      associated with rare coding sequence variation in the SCN10A gene, which encodes
      the voltage-gated sodium channel isoform NaV1.8 found primarily in peripheral
      nerves and to identify potentially disease-related mechanisms in high-priority
      rare variants using in-vitro electrophysiology. METHODS AND RESULTS: We re
      sequenced SCN10A in 274 patients with early onset AF from the Vanderbilt AF
      Registry to identify rare coding variants. Engineered variants were transiently
      expressed in ND7/23 cells and whole-cell voltage clamp experiments were conducted
      to elucidate their functional properties. Resequencing SCN10A identified 18
      heterozygous rare coding variants (minor allele frequency <=1%) in 18 (6.6%) AF
      probands. Four probands were carriers of two rare variants each and 14 were
      carriers of one coding variant. Based on evidence of co-segregation, initial
      assessment of functional importance, and presence in >=1 AF proband, three
      variants (417delK, A1886V, and the compound variant Y158D-R814H) were selected
      for functional studies. The 417delK variant displayed near absent current while
      A1886V and Y158D-R814H exhibited enhanced peak and late (INa-L) sodium currents;
      both Y158D and R818H individually contributed to this phenotype. CONCLUSION: Rare
      SCN10A variants encoding Nav1.8 were identified in 6.6% of patients with early
      onset AF. In-vitro electrophysiological studies demonstrated profoundly altered
      function in 3/3 high-priority variants. Collectively, these data strongly support
      the hypothesis that rare SCN10A variants may contribute to AF susceptibility.

PMID- 25053640
TI  - A move beyond screening is required to ensure adequate healthcare response for
      women who experience intimate partner violence.

PMID- 25053641
TI  - The STONE score can help diagnose urolithiasis and decrease the use of CT scans.

PMID- 25053642
TI  - Maternal body mass index increasing above 20 is associated with increased risk of
      miscarriage, stillbirth, neonatal death and postneonatal death.

PMID- 25053643
TI  - Alleviation of aluminium-induced cell rigidity by overexpression of OsPIN2 in
      rice roots.
AB  - Al-induced cell rigidity is one of the symptoms of Al toxicity, but the mechanism
      by which plants tolerate this toxicity is still unclear. In this study, we found
      that overexpression of OsPIN2, an auxin transporter gene, could alleviate Al
      induced cell rigidity in rice root apices. A freeze-thawing experiment showed
      that the Al-treated roots of wild-type (WT) plants had more damage in the
      epidermal and outer cortex cells than that found in lines overexpressing OsPIN2
      (OXs), and the freeze-disrupt coefficient was 2-fold higher in the former than in
      the latter. Furthermore, Al could induce aberrations of the cell wall-plasma
      membrane interface, which was more prominent in the epidermal cells of the
      elongation zone of the WT. Overexpressed OsPIN2 reduced Al-induced formation of
      reactive oxygen species and weakened Al-induced lipid peroxidation and
      lignification in roots. Compared with WT, a 16.6-32.6% lower Al-triggered
      hemicellulose 1 accumulation was observed in root apices of OXs, and 17.4-20.5%
      less Al accumulated in the cell wall of OXs. Furthermore, overexpression of
      OsPIN2 ameliorated the Al inhibitory effect on basipetal auxin transport and
      increased Al-induced IAA and proton release. Taken together, our results suggest
      that by decreasing the binding of Al to the cell wall and Al-targeted oxidative
      cellular damage, OXs lines show less Al-induced damage. By modulating PIN2-based
      auxin transport, IAA efflux, and cell wall acidification, lines overexpressing
      OsPIN2 alleviate Al-induced cell rigidity in the rice root apex.

PMID- 25053645
TI  - Relative contribution of shoot and ear photosynthesis to grain filling in wheat
      under good agronomical conditions assessed by differential organ delta13C.
AB  - During grain filling in C3 cereals, the shoot (particularly the flag leaf) and
      the ear are believed to play major roles as sources of assimilates. However, both
      the cost and the intrusive nature of most of the methodologies available to
      investigate this have prevented conclusive results being obtained. This study
      compared the carbon isotope composition (delta(13)C) in its natural abundance in
      mature kernels with the delta(13)C of the water-soluble fraction of the peduncle,
      glumes, and awns to assess the relative contribution of the shoot (understood as
      the whole set of photosynthetic organs below the peduncle) and ear to grain
      filling in a set of highly productive wheat lines from the International Maize
      and Wheat Improvement Center, Mexico, under good agronomic conditions. In overall
      terms, the contribution of the ear was greater in comparison with that of the
      shoot. The specific contribution of the flag leaf blade to grain filling was also
      assessed by comparing the delta(13)C of grains with the delta(13)C of the water
      soluble fraction of the flag leaf and the awns. The contribution of the flag leaf
      was minor, ranging between 3 and 18%. Complementary analyses performed such as
      gas-exchange rates and the accumulated water-soluble carbohydrates in both organs
      and light intercepted by the canopy at different strata suggested that the ear
      has a photosynthetic capacity at least comparable to that of the flag leaf. In
      this sense, selection for a higher contribution of ear photosynthesis to grain
      yield in breeding programmes could be addressed with the use of stable isotopes.

PMID- 25053644
TI  - Effect of exogenous methanol on glycolate oxidase and photorespiratory
      intermediates in cotton.
AB  - Application of methanol (MeOH) inhibits photorespiration and enhances growth and
      yield in C3 plants. However, the underlying cellular and molecular mechanisms are
      not clear. In this study, we investigated the effects of foliar application of
      MeOH (30%, v/v) on glycolate oxidase (GO) activity and photorespiratory
      intermediates in cotton leaves in a field experiment. MeOH treatment
      significantly inhibited GO activity (by 30% compared with the controls). We also
      found that endogenous glyoxylate, a photorespiratory intermediate, increased and
      glycine decreased significantly in MeOH-treated plants. Serine increased
      significantly in MeOH-treated plants. These results thus demonstrated that
      exogenous MeOH can modulate GO activity and the production of photorespiratory
      intermediates, and sheds new lights on our current understanding of how exogenous
      MeOH inhibits photorespiration and enhances the growth and yield of C3 plants
      such as cotton.

PMID- 25053646
TI  - Engineering alpha-amylase levels in wheat grain suggests a highly sophisticated
      level of carbohydrate regulation during development.
AB  - Wheat starch degradation requires the synergistic action of different amylolytic
      enzymes. Our spatio-temporal study of wheat alpha-amylases throughout grain
      development shows that AMY3 is the most abundant isoform compared with the other
      known alpha-amylases. Endosperm-specific over-expression of AMY3 resulted in an
      increase of total alpha-amylase activity in harvested grains. Unexpectedly,
      increased activity did not have a significant impact on starch content or
      composition but led to an increase of soluble carbohydrate (mainly sucrose) in
      dry grain. In AMY3 overexpression lines (A3OE), germination was slightly delayed
      and triacylglycerol (TAG) content was increased in the endosperm of mature grain.
      Despite increased AMY3 transcript and protein content throughout grain
      development, alterations of alpha-amylase activity and starch granule degradation
      were not detected until grain maturation, suggesting a post-translational
      inhibition of alpha-amylase activity in the endosperm during the starch filling
      period. These findings show unexpected effects of a high level of alpha-amylase
      on grain development and composition, notably in carbon partitioning and TAG
      accumulation, and suggest the presence of a hitherto unknown regulatory pathway
      during grain filling.

PMID- 25053647
TI  - Differential expression patterns of arabinogalactan proteins in Arabidopsis
      thaliana reproductive tissues.
AB  - Arabinogalactan proteins (AGPs) are heavily glycosylated proteins existing in all
      members of the plant kingdom and are differentially distributed through
      distinctive developmental stages. Here, we showed the individual distributions of
      specific Arabidopsis AGPs: AGP1, AGP9, AGP12, AGP15, and AGP23, throughout
      reproductive tissues and indicated their possible roles in several reproductive
      processes. AGP genes specifically expressed in female tissues were identified
      using available microarray data. This selection was confirmed by promoter
      analysis using multiple green fluorescent protein fusions to a nuclear
      localization signal, beta-glucuronidase fusions, and in situ hybridization as
      approaches to confirm the expression patterns of the AGPs. Promoter analysis
      allowed the detection of a specific and differential presence of these proteins
      along the pathway followed by the pollen tube during its journey to reach the egg
      and the central cell inside the embryo sac. AGP1 was expressed in the stigma,
      style, transmitting tract, and the chalazal and funiculus tissues of the ovules.
      AGP9 was present along the vasculature of the reproductive tissues and AGP12 was
      expressed in the stigmatic cells, chalazal and funiculus cells of the ovules, and
      in the septum. AGP15 was expressed in all pistil tissues, except in the
      transmitting tract, while AGP23 was specific to the pollen grain and pollen tube.
      The expression pattern of these AGPs provides new evidence for the detection of a
      subset of specific AGPs involved in plant reproductive processes, being of
      significance for this field of study. AGPs are prominent candidates for male
      female communication during reproduction.

PMID- 25053648
TI  - Arabidopsis membrane-associated acyl-CoA-binding protein ACBP1 is involved in
      stem cuticle formation.
AB  - The membrane-anchored Arabidopsis thaliana ACYL-COA-BINDING PROTEIN1 (AtACBP1)
      plays important roles in embryogenesis and abiotic stress responses, and
      interacts with long-chain (LC) acyl-CoA esters. Here, AtACBP1 function in stem
      cuticle formation was investigated. Transgenic Arabidopsis transformed with an
      AtACBP1pro::GUS construct revealed beta-glucuronidase (GUS) expression on the
      stem (but not leaf) surface, suggesting a specific role in stem cuticle
      formation. Isothermal titration calorimetry results revealed that (His)6-tagged
      recombinant AtACBP1 interacts with LC acyl-CoA esters (18:1-, 18:2-, and 18:3
      CoAs) and very-long-chain (VLC) acyl-CoA esters (24:0-, 25:0-, and 26:0-CoAs).
      VLC fatty acids have been previously demonstrated to act as precursors in wax
      biosynthesis. Gas chromatography (GC)-flame ionization detector (FID) and GC-mass
      spectrometry (MS) analyses revealed that an acbp1 mutant showed a reduction in
      stem and leaf cuticular wax and stem cutin monomer composition in comparison with
      the wild type (Col-0). Consequently, the acbp1 mutant showed fewer wax crystals
      on the stem surface in scanning electron microscopy and an irregular stem cuticle
      layer in transmission electron microscopy in comparison with the wild type. Also,
      the mutant stems consistently showed a decline in expression of cuticular wax and
      cutin biosynthetic genes in comparison with the wild type, and the mutant leaves
      were more susceptible to infection by the necrotrophic pathogen Botrytis cinerea.
      Taken together, these findings suggest that AtACBP1 participates in Arabidopsis
      stem cuticle formation by trafficking VLC acyl-CoAs.

PMID- 25053649
TI  - Resting-state functional connectivity of the nucleus accumbens in auditory and
      visual hallucinations in schizophrenia.
AB  - Both auditory hallucinations (AH) and visual hallucinations may occur in
      schizophrenia. One of the main hypotheses underlying their occurrence involves
      the increased activity of the mesolimbic pathway, which links the ventral
      tegmental area (VTA) and the nucleus accumbens (NAcc). However, the precise
      contribution of the mesolimbic pathway in hallucinations across various sensory
      modalities has not yet been explored. We compared the resting-state functional
      connectivity (rs-FC) of the NAcc among 16 schizophrenia patients with pure AH, 15
      with both visuoauditory hallucinations (VAH), and 14 without hallucinations
      (NoH). A between-group comparison was performed using random-effects ANCOVA (rs
      FC of the bilateral NAcc as the dependent variable, groups as the between
      subjects factor, age and Positive and Negative Syndrome Scale scores as
      covariates; q(false discovery rate [FDR]) < .05). Compared to the NoH group, the
      AH group exhibited significantly enhanced NAcc rs-FC with the left temporal
      superior gyrus, the cingulate gyri, and the VTA, whereas the VAH group, compared
      to the AH group, exhibited significantly enhanced NAcc rs-FC with the bilateral
      insula, putamen, parahippocampal gyri, and VTA. The strength in rs-FC between the
      NAcc and the VTA appeared to be positively associated with the presence of
      hallucinations, but the NAcc FC patterns changed with the complexity of these
      experiences (ie, 0, 1, or 2 sensory modalities), rather than with severity. This
      might support the aberrant salience hypothesis of schizophrenia. Moreover, these
      findings suggest that future clinical and neurobiological studies of
      hallucinations should evaluate not only the global severity of symptoms but also
      their sensorial features. 

PMID- 25053650
TI  - Cognitive mechanisms of change in delusions: an experimental investigation
      targeting reasoning to effect change in paranoia.
AB  - BACKGROUND: Given the evidence that reasoning biases contribute to delusional
      persistence and change, several research groups have made systematic efforts to
      modify them. The current experiment tested the hypothesis that targeting
      reasoning biases would result in change in delusions. METHODS: One hundred and
      one participants with current delusions and schizophrenia spectrum psychosis were
      randomly allocated to a brief computerized reasoning training intervention or to
      a control condition involving computer-based activities of similar duration. The
      primary hypotheses tested were that the reasoning training intervention, would
      improve (1) data gathering and belief flexibility and (2) delusional thinking,
      specifically paranoia. We then tested whether the changes in paranoia were
      mediated by changes in data gathering and flexibility, and whether working memory
      and negative symptoms moderated any intervention effects. RESULTS: On an
      intention-to-treat analysis, there were significant improvements in state
      paranoia and reasoning in the experimental compared with the control condition.
      There was evidence that changes in reasoning mediated changes in paranoia,
      although this effect fell just outside the conventional level of significance
      after adjustment for baseline confounders. Working memory and negative symptoms
      significantly moderated the effects of the intervention on reasoning. CONCLUSION:
      The study demonstrated the effectiveness of a brief reasoning intervention in
      improving both reasoning processes and paranoia. It thereby provides proof-of
      concept evidence that reasoning is a promising intermediary target in
      interventions to ameliorate delusions, and thus supports the value of developing
      this approach as a longer therapeutic intervention.

PMID- 25053651
TI  - Early developmental disturbances of cortical inhibitory neurons: contribution to
      cognitive deficits in schizophrenia.
AB  - Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive
      impairments have been linked to disturbances in inhibitory (gamma-aminobutyric
      acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present
      well before the onset of psychotic symptoms and have been detected in early
      childhood with developmental delays reported during the first year of life. These
      data suggest that the pathogenetic process that produces dysfunction of
      prefrontal GABA neurons in schizophrenia may be related to altered prenatal
      development. Interestingly, adult postmortem schizophrenia brain tissue studies
      have provided evidence consistent with a disease process that affects different
      stages of prenatal development of specific subpopulations of prefrontal GABA
      neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic
      specification) of distinct subpopulations of cortical GABA neurons is
      differentially regulated by a host of transcription factors, chemokine receptors,
      and other molecular markers. In this review article, we propose a strategy to
      investigate how alterations in the expression of these developmental regulators
      of subpopulations of cortical GABA neurons may contribute to the pathogenesis of
      cortical GABA neuron dysfunction and consequently cognitive impairments in
      schizophrenia. 

PMID- 25053652
TI  - Does population density and neighborhood deprivation predict schizophrenia? A
      nationwide Swedish family-based study of 2.4 million individuals.
AB  - People living in densely populated and socially disorganized areas have higher
      rates of psychiatric morbidity, but the potential causal status of such factors
      is uncertain. We used nationwide Swedish longitudinal registry data to identify
      all children born 1967-1989 (n = 2361585), including separate datasets for all
      cousins (n = 1715059) and siblings (n = 1667894). The nature of the associations
      between population density and neighborhood deprivation and individual risk for a
      schizophrenia diagnosis was investigated while adjusting for unobserved familial
      risk factors (through cousin and sibling comparisons) and then compared with
      similar associations for depression. We generated familial pedigree structures
      using the Multi-Generation Registry and identified study participants with
      schizophrenia and depression using the National Patient Registry. Fixed-effects
      logistic regression models were used to study within-family estimates. Population
      density, measured as ln(population size/km(2)), at age 15 predicted subsequent
      schizophrenia in the population (OR = 1.10; 95% CI: 1.09; 1.11). Unobserved
      familial risk factors shared by cousins within extended families attenuated the
      association (1.06; 1.03; 1.10), and the link disappeared entirely within nuclear
      families (1.02; 0.97; 1.08). Similar results were found for neighborhood
      deprivation as predictor and for depression as outcome. Sensitivity tests
      demonstrated that timing and accumulation effects of the exposures (mean scores
      across birth, ages 1-5, 6-10, and 11-15 years) did not alter the findings. Excess
      risks of psychiatric morbidity, particularly schizophrenia, in densely populated
      and socioeconomically deprived Swedish neighborhoods appear, therefore, to result
      primarily from unobserved familial selection factors. Previous studies may have
      overemphasized the etiological importance of these environmental factors. 

PMID- 25053653
TI  - Apathy but not diminished expression in schizophrenia is associated with
      discounting of monetary rewards by physical effort.
AB  - Negative symptoms in schizophrenia have been grouped into the 2 factors of apathy
      and diminished expression, which might be caused by separable pathophysiological
      mechanisms. Recently, it has been proposed that apathy could be due to
      dysfunctional integration of reward and effort during decision making. We asked
      whether apathy in particular is associated with stronger devaluation
      ("discounting") of monetary rewards that require physical effort. Thirty-one
      patients with schizophrenia and 20 healthy control participants performed a
      computerized effort discounting task in which they could choose to exert physical
      effort on a handgrip to obtain monetary rewards. This procedure yields an
      individual measure for the strength of effort discounting. The degree of effort
      discounting was strongly correlated with apathy, but not with diminished
      expression. Importantly, the association between apathy and effort discounting
      was not driven by cognitive ability, antipsychotic medication, or other clinical
      and demographic variables. This study provides the first evidence for a highly
      specific association of apathy with effort-based decision making in patients with
      schizophrenia. Within a translational framework, the present effort discounting
      task could provide a bridge between apathy as a psychopathological phenomenon and
      established behavioral tasks to address similar states in animals. 

PMID- 25053656
TI  - Molecular phylogeny of sequenced saccharomycetes reveals polyphyly of the
      alternative yeast codon usage.
AB  - The universal genetic code defines the translation of nucleotide triplets, called
      codons, into amino acids. In many Saccharomycetes a unique alteration of this
      code affects the translation of the CUG codon, which is normally translated as
      leucine. Most of the species encoding CUG alternatively as serine belong to the
      Candida genus and were grouped into a so-called CTG clade. However, the "Candida
      genus" is not a monophyletic group and several Candida species are known to use
      the standard CUG translation. The codon identity could have been changed in a
      single branch, the ancestor of the Candida, or to several branches independently
      leading to a polyphyletic alternative yeast codon usage (AYCU). In order to
      resolve the monophyly or polyphyly of the AYCU, we performed a phylogenomics
      analysis of 26 motor and cytoskeletal proteins from 60 sequenced yeast species.
      By investigating the CUG codon positions with respect to sequence conservation at
      the respective alignment positions we were able to unambiguously assign the
      standard code or AYCU. Quantitative analysis of the highly conserved leucine and
      serine alignment positions showed, that 61.1% and 17% of the CUG codons coding
      for leucine and serine, respectively, are at highly conserved positions, while
      only 0.6% and 2.3% of the CUG codons, respectively, are at positions conserved in
      the respective other amino acid. Plotting the codon usage onto the phylogenetic
      tree revealed the polyphyly of the AYCU with Pachysolen tannophilus and the CTG
      clade branching independently within a time span of 30 to 100 Mya.

PMID- 25053654
TI  - Jumping to conclusions, neuropsychological functioning, and delusional beliefs in
      first episode psychosis.
AB  - BACKGROUND: The "jumping to conclusions" (JTC) data-gathering bias is implicated
      in the development and maintenance of psychosis but has only recently been
      studied in first episode psychosis (FEP). In this study, we set out to establish
      the relationship of JTC in FEP with delusions and neuropsychological functioning.
      METHODS: One hundred and eight FEP patients and 101 age-matched controls
      completed assessments of delusions, general intelligence (IQ), working memory
      (WM), and JTC (the probabilistic reasoning "beads" task). RESULTS: Half the FEP
      participants jumped to conclusions on at least 1 task, compared with 25% of
      controls (OR range 2.1 to 3.9; 95% CI range 1.5 to 8.0, P values <= .02). JTC was
      associated with clinical, but not nonclinical delusion severity, and with
      neuropsychological functioning, irrespective of clinical status. Both IQ and
      delusion severity, but not WM, were independently associated with JTC in the FEP
      group. CONCLUSIONS: JTC is present in FEP. The specific association of JTC with
      clinical delusions supports a state, maintaining role for the bias. The
      associations of JTC with neuropsychological functioning indicate a separable,
      trait aspect to the bias, which may confer vulnerability to psychosis. The work
      has potential to inform emerging interventions targeting reasoning biases in
      early psychosis.

PMID- 25053658
TI  - What are seasonal and meteorological factors are associated with the number of
      attendees at a sexual health service? An observational study between 2002-2012.
AB  - BACKGROUND: Open access to sexual health services may be inefficient if there are
      substantial unpredictable fluctuations in presentations. Our aim was to determine
      whether the number of presentations over the last 11 years was associated with
      certain factors. METHODS: This study involved all individuals presenting to
      Melbourne Sexual Health Centre (MSHC) from 2002 to 2012. The outcome measure was
      the number of presentations during a clinical session (half day). RESULTS: There
      were 270,070 presentations to the clinic among 86,717 individuals. The factors
      associated with the largest difference in mean presentations per session were
      morning or afternoon (60 vs 51 per session), days of the week (57-67 per
      session), months of the year (93-112 per day), year (77-131 per day), maximum
      temperatures of <15  degrees C vs. >=30  degrees C (56-62 per morning session)
      and 5 working days after holiday periods (61 vs 54). A multiple linear regression
      model using these factors explained 64% of the variation in attendances per
      session. Peak attendance rates (>90th centile) were also strongly correlated with
      these same variables. Higher-risk heterosexuals (<=25 years of age) attended more
      commonly in the afternoons (37% of heterosexuals) than in the mornings (30%). No
      factor other than year of attendance substantially influenced the proportion of
      higher-risk men who have sex with men (MSM) (>=10 partners per year) who
      attended. CONCLUSIONS: A considerable proportion of the variability in
      presentations was explained by known factors that could predict client
      presentations to sexual health services and therefore allow optimal allocation of
      resources to match demand.

PMID- 25053659
TI  - Catheter ablation of atrial fibrillation: an update.
AB  - Catheter ablation of atrial fibrillation (AF) is now an important therapeutic
      modality for patients with AF. There is considerable evidence available from
      several prospective randomized trials demonstrating that catheter ablation of AF
      is superior to antiarrhythmic drug therapy in controlling AF and that AF ablation
      improves quality of life substantially. This is especially true for patients with
      paroxysmal AF without other severe comorbidities. Catheter ablation is indicated
      for treatment of patients with symptomatic AF in whom one or more attempts at
      class 1 or 3 antiarrhythmic drug therapy have failed. Although current guidelines
      state that is appropriate to perform catheter ablation as a first-line therapy in
      selected patients, in our clinical practice this is rare. This reflects a number
      of important realities concerning the field of AF ablation. Catheter ablation of
      AF is a challenging and complex procedure, which is not free of the risk of
      potentially life-threatening complications, such as an atrio-oesophageal fistula,
      stroke, and cardiac tamponade. Although these major complications are rare and
      their rate is falling, they must be considered by both patients and physicians.
      The progress made and the new developments on the horizon in the field of AF
      catheter ablation are remarkable. When radiofrequency catheter ablation was first
      introduced in the late 1980s, few would have predicted that catheter ablation of
      AF would emerge as the most commonly performed ablation procedure in most major
      hospitals. 

PMID- 25053661
TI  - Intraaortic balloon pump boon for off-pump coronary artery bypass grafting.
AB  - BACKGROUND: Off-pump coronary artery bypass techniques have evolved in the past
      decade, but there are some concerns about hemodynamic decompensation requiring
      conversion to cardiopulmonary bypass. These conversions are associated with
      higher morbidity and mortality. We use an intraaortic balloon pump to treat
      ischemia-induced hemodynamic instability and arrhythmias during off-pump coronary
      artery bypass. The objective of this study was to assess the impact of
      intraaortic balloon pump use in off-pump coronary artery bypass to prevent
      emergency conversion to cardiopulmonary bypass. METHODS: Data of 529 consecutive
      unselected patients who underwent isolated coronary artery bypass were included
      in this retrospective study of prospectively collected data and operation notes.
      Complete revascularization was performed using an off-pump technique. All
      arterial grafts using bilateral internal mammary arteries, and aortic no-touch
      technique were preferred. If the clinical situation demanded, vein grafts were
      used. During the procedure, any hemodynamic compromise not responding to
      conventional inotropic therapy was treated with intraaortic balloon pump
      insertion. RESULTS: Complete revascularization was possible in all 529 patients.
      An intraaortic balloon pump was inserted in 33 (6.2%) patients to treat
      hemodynamic instability; in all cases, conversion to cardiopulmonary bypass was
      avoided and complete revascularization was achieved. CONCLUSION: For treating
      hemodynamic instability during off-pump coronary artery bypass, we recommend
      intraaortic balloon pump insertion as the preferred bail-out method rather than
      conversion to cardiopulmonary bypass.

PMID- 25053662
TI  - Bronchial artery embolization for massive hemoptysis: long-term follow-up.
AB  - AIM: Bronchial artery angiography with embolization has become a mainstay in the
      treatment of massive hemoptysis. Whereas the immediate success rate is high, the
      reported long-term success rate varies widely among different groups. We aimed to
      explore the long-term outcome and clinical predictors associated with recurrent
      bleeding following bronchial artery embolization. METHODS: We reviewed the
      clinical characteristics, underlying etiologies, procedure details, and outcome
      of bronchial artery embolization performed for massive hemoptysis between 1999
      and 2012. RESULTS: All 52 consecutive patients treated by bronchial artery
      embolization during the study period were included. The major etiologies of
      massive hemoptysis were bronchiectasis (mostly post-infectious) in 53.8%, and
      primary and metastatic lung cancer in 30.8%. The immediate success rate was high
      (48/52; 92%). Of 45 patients who survived more than 24 hours following bronchial
      artery embolization, recurrent bleeding did not occur in 19 (42.2%) during a
      median follow-up period of 60 months (range 6-130 months). Bleeding recurred in
      26 (57.7%); within 30 days in 15 (33.3%) and after 1 month in the other 11
      (24.4%). The average time to onset of early and late repeat bleeding was 2 and
      506 days, respectively. Idiopathic bronchiectasis and lung cancer were associated
      with a high likelihood of late bleeding recurrence. CONCLUSIONS: Bronchial artery
      embolization is an effective immediate treatment for massive hemoptysis. Because
      the bleeding recurrence rate is high in patients with lung cancer or idiopathic
      bronchiectasis, surgery should be considered in these patients following initial
      stabilization by bronchial artery embolization. For other underlying etiologies,
      the long-term outcome is excellent.

PMID- 25053657
TI  - MicroRNA in teleost fish.
AB  - MicroRNAs (miRNAs) are transcriptional and posttranscriptional regulators
      involved in nearly all known biological processes in distant eukaryotic clades.
      Their discovery and functional characterization have broadened our understanding
      of biological regulatory mechanisms in animals and plants. They show both
      evolutionary conserved and unique features across Metazoa. Here, we present the
      current status of the knowledge about the role of miRNA in development, growth,
      and physiology of teleost fishes, in comparison to other vertebrates. Infraclass
      Teleostei is the most abundant group among vertebrate lineage. Fish are an
      important component of aquatic ecosystems and human life, being the prolific
      source of animal proteins worldwide and a vertebrate model for biomedical
      research. We review miRNA biogenesis, regulation, modifications, and mechanisms
      of action. Specific sections are devoted to the role of miRNA in teleost
      development, organogenesis, tissue differentiation, growth, regeneration,
      reproduction, endocrine system, and responses to environmental stimuli. Each
      section discusses gaps in the current knowledge and pinpoints the future
      directions of research on miRNA in teleosts. 

PMID- 25053660
TI  - Homozygous familial hypercholesterolaemia: new insights and guidance for
      clinicians to improve detection and clinical management. A position paper from
      the Consensus Panel on Familial Hypercholesterolaemia of the European
      Atherosclerosis Society.
AB  - AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening
      condition characterized by markedly elevated circulating levels of low-density
      lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic
      cardiovascular disease (ACVD). Given recent insights into the heterogeneity of
      genetic defects and clinical phenotype of HoFH, and the availability of new
      therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of
      the European Atherosclerosis Society (EAS) critically reviewed available data
      with the aim of providing clinical guidance for the recognition and management of
      HoFH. METHODS AND RESULTS: Early diagnosis of HoFH and prompt initiation of diet
      and lipid-lowering therapy are critical. Genetic testing may provide a definitive
      diagnosis, but if unavailable, markedly elevated LDL-C levels together with
      cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels
      consistent with heterozygous FH in both parents, are suggestive of HoFH. We
      recommend that patients with suspected HoFH are promptly referred to specialist
      centres for a comprehensive ACVD evaluation and clinical management. Lifestyle
      intervention and maximal statin therapy are the mainstays of treatment, ideally
      started in the first year of life or at an initial diagnosis, often with
      ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C
      targets, adjunctive lipoprotein apheresis is recommended where available,
      preferably started by age 5 and no later than 8 years. The number of therapeutic
      approaches has increased following approval of lomitapide and mipomersen for
      HoFH. Given the severity of ACVD, we recommend regular follow-up, including
      Doppler echocardiographic evaluation of the heart and aorta annually, stress
      testing and, if available, computed tomography coronary angiography every 5
      years, or less if deemed necessary. CONCLUSION: This EAS Consensus Panel
      highlights the need for early identification of HoFH patients, prompt referral to
      specialized centres, and early initiation of appropriate treatment. These
      recommendations offer guidance for a wide spectrum of clinicians who are often
      the first to identify patients with suspected HoFH.

PMID- 25053663
TI  - Minimally invasive mitral valve surgery via minithoracotomy and direct
      cannulation.
AB  - BACKGROUND: To reduce the morbidity of mitral valve operations, a right
      anterolateral minithoracotomy under direct vision was introduced. We report our
      experience with this procedure. METHODS: From July 2001 to December 2013, 320
      consecutive patients underwent direct minimally invasive mitral valve surgery
      through a right anterolateral minithoracotomy at our institution. Evidence of
      rheumatic disease was observed in 231 (72%) patients, and 89 (28%) repaired
      valves had myxomatous changes. Tricuspid valve repair was performed in 80 (25%)
      patients and radiofrequency ablation in 80 (25%) with chronic atrial
      fibrillation. All cannulas were introduced through the thoracotomy incision,
      eliminating femoral cannulation. No new instruments, retractors, or ports were
      used. Pleural and pericardial drainage was accomplished through a single drain.
      RESULTS: There was no hospital death. Conversion to sternotomy was needed in 3
      patients because we were unable to obtain satisfactory arterial cannulation.
      Eight patients required reoperation: 7 for mitral insufficiency and one for
      postoperative bleeding. Mean cardiopulmonary bypass and crossclamp times were
      55.3 +/- 17.0 and 43.0 +/- 13.4 min, respectively. Mean intensive care unit stay
      was 29 h, and hospital stay was 4.3 days. CONCLUSIONS: Based on our experience,
      this minimally invasive approach is safe, rapid, cost-effective, and more
      comfortable for the patients, in addition to its cosmetic benefits. It may be the
      preferred approach in young females.

PMID- 25053664
TI  - Asymmetric neuroblast divisions producing apoptotic cells require the cytohesin
      GRP-1 in Caenorhabditis elegans.
AB  - Cytohesins are Arf guanine nucleotide exchange factors (GEFs) that regulate
      membrane trafficking and actin cytoskeletal dynamics. We report here that GRP-1,
      the sole Caenorhabditis elegans cytohesin, controls the asymmetric divisions of
      certain neuroblasts that divide to produce a larger neuronal precursor or neuron
      and a smaller cell fated to die. In the Q neuroblast lineage, loss of GRP-1 led
      to the production of daughter cells that are more similar in size and to the
      transformation of the normally apoptotic daughter into its sister, resulting in
      the production of extra neurons. Genetic interactions suggest that GRP-1
      functions with the previously described Arf GAP CNT-2 and two other Arf GEFs, EFA
      6 and BRIS-1, to regulate the activity of Arf GTPases. In agreement with this
      model, we show that GRP-1's GEF activity, mediated by its SEC7 domain, is
      necessary for the posterior Q cell (Q.p) neuroblast division and that both GRP-1
      and CNT-2 function in the Q.posterior Q daughter cell (Q.p) to promote its
      asymmetry. Although functional GFP-tagged GRP-1 proteins localized to the
      nucleus, the extra cell defects were rescued by targeting the Arf GEF activity of
      GRP-1 to the plasma membrane, suggesting that GRP-1 acts at the plasma membrane.
      The detection of endogenous GRP-1 protein at cytokinesis remnants, or midbodies,
      is consistent with GRP-1 functioning at the plasma membrane and perhaps at the
      cytokinetic furrow to promote the asymmetry of the divisions that require its
      function.

PMID- 25053666
TI  - Spontaneous closure of a dural arteriovenous fistula.
AB  - Spontaneous closure of a dural arteriovenous fistula (dAVF) is a rare condition
      and only a few cases have been reported since its first description in 1976. We
      report delayed and progressive spontaneous closure of a dAVF after massive
      intracerebral hemorrhage documented by angiographic studies before and after
      bleeding. To our knowledge, this is the first report to document gradual closure
      of a dAVF by serial angiographic studies. The mechanism of spontaneous closure of
      dAVFs has not been fully elucidated. We suggest different factors for
      consideration from previously published data and show how each of these factors
      can influence the others. 

PMID- 25053665
TI  - DNA helicase HIM-6/BLM both promotes MutSgamma-dependent crossovers and
      antagonizes MutSgamma-independent interhomolog associations during caenorhabditis
      elegans meiosis.
AB  - Meiotic recombination is initiated by the programmed induction of double-strand
      DNA breaks (DSBs), lesions that pose a potential threat to the genome. A subset
      of the DSBs induced during meiotic prophase become designated to be repaired by a
      pathway that specifically yields interhomolog crossovers (COs), which mature into
      chiasmata that temporarily connect the homologs to ensure their proper
      segregation at meiosis I. The remaining DSBs must be repaired by other mechanisms
      to restore genomic integrity prior to the meiotic divisions. Here we show that
      HIM-6, the Caenorhabditis elegans ortholog of the RecQ family DNA helicase BLM,
      functions in both of these processes. We show that him-6 mutants are competent to
      load the MutSgamma complex at multiple potential CO sites, to generate
      intermediates that fulfill the requirements of monitoring mechanisms that enable
      meiotic progression, and to accomplish and robustly regulate CO designation.
      However, recombination events at a subset of CO-designated sites fail to mature
      into COs and chiasmata, indicating a pro-CO role for HIM-6/BLM that manifests
      itself late in the CO pathway. Moreover, we find that in addition to promoting
      COs, HIM-6 plays a role in eliminating and/or preventing the formation of
      persistent MutSgamma-independent associations between homologous chromosomes. We
      propose that HIM-6/BLM enforces biased outcomes of recombination events to ensure
      that both (a) CO-designated recombination intermediates are reliably resolved as
      COs and (b) other recombination intermediates reliably mature into noncrossovers
      in a timely manner.

PMID- 25053667
TI  - Onyx embolization of an avulsed thalamoperforator following endoscopic colloid
      cyst and lamina terminalis fenestration.
AB  - A patient presented with headaches and was found to have a colloid cyst in the
      third ventricle and ventriculomegaly. The patient underwent endoscopic colloid
      cyst resection and third ventriculostomy without incidence. Prior to emergence, a
      blown right pupil was acutely noted, and bright red blood emanated from the
      ventricular drain that was routinely placed in the endoscopy tract at the
      conclusion of the procedure. CTangiography demonstrated active extravasation from
      the pre-pontine cistern into the third ventricle and subarachnoid space.
      Emergency DSA confirmed active extravasation from an avulsed thalamoperforator
      arising from the proximal right P1 posterior cerebral artery, which was
      immediately embolized without incident. 

PMID- 25053668
TI  - Phenytoin-induced severe gingival overgrowth in a child.
AB  - Gingival enlargement or overgrowth (GO) is a common complication of the
      anticonvulsant drug phenytoin (PHT). GO is evident in almost half of the patients
      receiving PHT therapy. PHT-induced gingival overgrowth (PGO) is more common in
      children than in adults and affects both males and females equally. PGO may vary
      from mild to severe and does not seem to be dose dependant. It is supposed that
      PHT and its metabolites cause a direct effect on the periodontal tissues;
      however, poor oral hygiene may contribute to the severity of gingival
      inflammation in patients with PGO. Management of PGO includes meticulous oral
      hygiene practice to reduce inflammation and surgical excision of the overgrown
      tissue, known as gingivectomy. We present a case of PHT-induced severe GO in a 10
      year-old boy and discuss the clinical features, aetiology, pathogenesis and
      management of PGO. 

PMID- 25053669
TI  - A prophylactic fresh frozen plasma transfusion leads to a possible case of
      transfusion-related acute lung injury.
AB  - A 39-year-old man with cholangiocarcinoma presented with fever and abdominal
      pain. He was hypotensive, jaundiced and had right upper quadrant tenderness.
      Laboratory testing showed a leucocytosis, elevated liver function tests, total
      bilirubin and International Normalised Ratio (INR). Given the concern for
      cholangitis, the patient was given antibiotics and three units of fresh frozen
      plasma (FFP) before biliary drain placement. After drain placement, and within 3
      h of receiving blood products, the patient became tachypnoeic and hypoxic with a
      chest X-ray revealing new bilateral airspace disease. The rapid development of
      respiratory distress was determined to most likely be transfusion-related acute
      lung injury (TRALI). He rapidly progressed to intubation and required 100% FiO2,
      high positive-end expiratory pressure (PEEP) and intermittent-prone ventilation
      for 48 h but eventually recovered and was extubated. TRALI is an under-recognised
      aetiology for respiratory distress in the critically ill. Adopting a conservative
      transfusion strategy may prevent TRALI. 

PMID- 25053670
TI  - Silent diabetes mellitus, periodontitis and a new case of thalamic abscess.
AB  - Brain abscess is an unusual complication of uncontrolled diabetes. A solitary
      thalamic abscess is an uncommon type of brain abscess. We report a case of
      thalamic abscess, whereupon diabetes mellitus and periodontitis were diagnosed.
      The diagnosis and management of thalamic abscess, and the interplay of type 2
      diabetes and periodontitis are discussed. A 56-year-old, Caucasian, man with no
      medical or travel history, presented with 5-day symptoms of meningeal irritation.
      Body mass index 30.6 kg/m(2). CT demonstrated a solitary midline lesion with
      neoplasia as a differential diagnosis. It was biopsied and cultures grew
      Streptococcus milleri. He was treated by stereotactic puncture, external drainage
      and targeted intrathecal and systemic antibiotic therapy. HIV negative but
      glycated haemoglobin (HbA1c) 10.7% (93 mmol/mol). Dental examination revealed a
      small molar abscess. Radiological resolution of the thalamic abscess occurred
      within 2 months. Diabetes improved with 7 weeks of insulin, and maintained on
      metformin, HbA1c 6.9% (51 mmol/mol). There was no residual neurological
      disability. 

PMID- 25053671
TI  - Spontaneous regression of a biopsy confirmed hepatocellular carcinoma.
AB  - A 74-year-old woman was diagnosed with histologically proven multiple bilobar
      hepatocellular carcinomas (HCC) in 2012. The lesions were inoperable and a repeat
      CT scan prior to starting chemotherapy revealed spontaneous regression of these
      lesions. Subsequent repeat scans have revealed continued regression of these
      lesions despite no active treatment. The case is presented with a literature
      review and discussion summarising the possible aetiologies of this phenomenon. 

PMID- 25053672
TI  - Recurrent hypoglycaemia in a patient with type 1 diabetes.

PMID- 25053673
TI  - Frames in contestation: gendering domestic violence policies in five central and
      eastern European countries.
AB  - The article looks at the translation of international norms on domestic violence
      to the national level in five Central and Eastern European countries. It argues
      that translation brings a concept of domestic violence, which stretches gender
      equality ideas underpinning international norms so as to be easier to endorse by
      mainstream policy actors, and results in policies framed in degendered individual
      rights terms. The potential for keeping gender equality in focus is then
      guaranteed by gendering policy processes through empowerment of gender equality
      actors at all stages. Absence of ownership of the policy by gender equality
      actors risks co-optation by frames contesting gender equality. 

PMID- 25053674
TI  - Joint association of genome-wide association study-identified susceptibility loci
      and dietary patterns in risk of renal cell carcinoma among non-Hispanic whites.
AB  - Dietary factors may affect risk of renal cell carcinoma (RCC). In an ongoing case
      control study of RCC initiated in Houston, Texas, in 2002, we identified 3
      empirically derived dietary patterns: "fruits and vegetables,"
      "American/Western," and "Tex-Mex." Among 659 RCC cases and 699 controls, we
      evaluated associations of these dietary patterns with RCC risk and whether the
      associations varied by obesity status, smoking status, physical activity level,
      history of hypertension, and genetic variants previously identified via genome
      wide association studies. Among persons in the highest categories of adherence
      versus the lowest, the "fruits and vegetables" dietary pattern was associated
      with an approximately 50% lower RCC risk (Ptrend < 0.001), while
      "American/Western" dietary pattern scores were positively associated with a 2
      fold higher risk (Ptrend < 0.001). We observed synergistic interaction between
      the American/Western pattern and hypertension status: The odds ratio (highest
      tertile vs. lowest) among persons with hypertension was 2.23 (95% confidence
      interval: 1.43, 3.45), as compared with 1.76 (95% confidence interval: 1.16,
      2.70) among persons without hypertension (additive Pinteraction = 0.01). A
      variant (rs718314) in the inositol 1,4,5-trisphosphate receptor, type 2 gene
      (ITPR2) was found to interact with the American/Western dietary pattern in
      relation to RCC risk (additive Pinteraction = 0.03). ITPR2 has been shown to
      affect nutrient metabolism and central obesity. Dietary patterns, genetic
      variants, and host characteristics may individually and jointly influence
      susceptibility to RCC. 

PMID- 25053677
TI  - High-Sensitivity C-Reactive Protein and Statin Initiation.
AB  - The assessment of cardiovascular risk and treatment of cardiovascular diseases
      are major public health issues worldwide. Inflammation is now recognized as a key
      regulatory process that links multiple risk factors for atherosclerosis. The
      substantial number of patients having cardiovascular events lack commonly
      established risk factors. The utility of high-sensitivity C-reactive protein
      (hsCRP), a circulating biomarker related to inflammation, may provide additional
      information in risk prediction. This review will consider the impact of hsCRP
      level on initiation of statin therapy. 

PMID- 25053675
TI  - Extreme expansion of the olfactory receptor gene repertoire in African elephants
      and evolutionary dynamics of orthologous gene groups in 13 placental mammals.
AB  - Olfactory receptors (ORs) detect odors in the environment, and OR genes
      constitute the largest multigene family in mammals. Numbers of OR genes vary
      greatly among species--reflecting the respective species' lifestyles--and this
      variation is caused by frequent gene gains and losses during evolution. However,
      whether the extent of gene gains/losses varies among individual gene lineages and
      what might generate such variation is unknown. To answer these questions, we used
      a newly developed phylogeny-based method to classify >10,000 intact OR genes from
      13 placental mammal species into 781 orthologous gene groups (OGGs); we then
      compared the OGGs. Interestingly, African elephants had a surprisingly large
      repertoire (~ 2000) of functional OR genes encoded in enlarged gene clusters.
      Additionally, OR gene lineages that experienced more gene duplication had weaker
      purifying selection, and Class II OR genes have evolved more dynamically than
      those in Class I. Some OGGs were highly expanded in a lineage-specific manner,
      while only three OGGs showed complete one-to-one orthology among the 13 species
      without any gene gains/losses. These three OGGs also exhibited highly conserved
      amino acid sequences; therefore, ORs in these OGGs may have physiologically
      important functions common to every placental mammal. This study provides a basis
      for inferring OR functions from evolutionary trajectory.

PMID- 25053676
TI  - Vitamin D and Dysfunctional Adipose Tissue in Obesity.
AB  - Vitamin D deficiency and dysfunctional adipose tissue are involved in the
      development of cardiometabolic disturbances (eg, hypertension, insulin
      resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated
      the relation between vitamin D and adipocytokines derived from adipose tissue. We
      studied 50 obese individuals who were classified into different subgroups
      according to medians of observed anthropometric parameters (body mass index, body
      fat percentage, waist circumference, and trunk fat mass). There was a negative
      correlation between vitamin D level and leptin and resistin (r = -.61, P < .01),
      while a positive association with adiponectin concentrations was found (r = .7, P
      < .001). Trend estimation showed that increase in vitamin D level is accompanied
      by intensive increase in adiponectin concentrations (growth coefficient: 12.13).
      In conclusion, a positive trend was established between vitamin D and the
      protective adipocytokine adiponectin. The clinical relevance of this relationship
      needs to be investigated in larger studies. 

PMID- 25053678
TI  - A biomarker for metastatic colorectal cancer and treatment goals.

PMID- 25053679
TI  - Serum matrix metalloproteinase-9 levels in acute coronary syndrome patients with
      and without hyperglycemia.
AB  - AIM: to determine the difference in serum matrix metalloproteinase-9 (MMP-9)
      levels among acute coronary syndrome patients with and without hyperglycemia.
      METHODS: this study was a cross-sectional study on patients with acute coronary
      syndrome admitted to ICCU of Dr.Sardjito Hospital Yogyakarta Indonesia.
      Measurements of blood glucose level were performed on hospital admission, while
      measurement of MMP-9 level was performed upon arrival at the ICCU. Hyperglycemia
      was defined as a random blood glucose level of >140 mg/dL. Student's t test was
      performed to analyze the difference of MMP-9 level between subjects with and
      without hyperglycemia. RESULTS: of 72 enrolled subjects, there were 34 subjects
      with hyperglycemia and 38 subjects without hyperglycemia. The mean blood glucose
      level was significantly different in subjects with hyperglycemia as compared to
      those without hyperglycemia (204.4+/-92.16 vs. 108.93+/-19.1 mg/dL, p=0.0001).
      The mean MMP-9 level in subjects with hyperglycemia was significantly higher than
      those without hyperglycemia (1574+/-573.61 vs. 1370+/-573.66 ng/mL, p=0.025). The
      prevalence ratio of high MMP-9 level among subjects with hyperglycemia was 2.88
      (95% CI: 1.16-7.14), p=0.004. CONCLUSION: serum MMP-9 level in patients suffering
      from acute coronary syndrome with hyperglycemia was significantly higher than
      those without hyperglycemia.

PMID- 25053680
TI  - Reference equation for prediction of a total distance during six-minute walk test
      using Indonesian anthropometrics.
AB  - AIM: to develop a reference equation for prediction of the total distance walk
      using Indonesian anthropometrics of sedentary healthy subjects. Subsequently, the
      prediction obtained was compared to those calculated by the Caucasian-based
      Enright prediction equation. METHODS: the cross-sectional study was conducted
      among 123 healthy Indonesian adults with sedentary life style (58 male and 65
      female subjects in an age range between 18 and 50 years). Heart rate was recorded
      using Polar with expectation in the sub-maximal zone (120-170 beats per minute).
      The subjects performed two six-minute walk tests, the first one on a 15-meter
      track according to the protocol developed by the investigator. The second walk
      was carried out on Biodex(r)gait trainer as gold standard. RESULTS: an average
      total distance of 547+/-54.24 m was found, not significantly different from the
      gold standard of 544.72+/-54.11 m (p>0.05). Multiple regression analysis was
      performed to develop the new equation. CONCLUSION: the reference equation for
      prediction of the total distance using Indonesian anthropometrics is more
      applicable in Indonesia.

PMID- 25053681
TI  - Profile of PRMT-1 gene polymorphism in hemodialysis patients with increased ADMA
      levels.
AB  - AIM: to determine the distribution of PRMT-1 gene polymorphism and ADMA levels
      among continuing hemodialysis patients. METHODS: genotyping of PRMT-1
      polymorphism was performed in 57 hemodialysis patients at Al Irsjad Hospital. All
      participants were recruited for physical examination, questionnaire, and
      collection of 5 mL fasting venous blood. The blood was treated with phenol
      chloroform extraction of genomic DNA. The candidate's single nucleotide
      polymorphisms (SNPs) were genotyped by using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). The ADMA plasma levels was
      determined by ELISA and all biochemical indicators of serum were examined.
      RESULTS: fifty-seven hemodialysis patients participated in our study, 54 (95.4%)
      of them had increased ADMA plasma levels. DNA sequencing analysis of 13 patients
      showed a suspected PRMT-1 gene polymorphism at sequence 5837 as there were
      different genotypes between C and G. CONCLUSION: the increased levels of ADMA
      might be caused by PRMT-1 gene polymorphism.

PMID- 25053682
TI  - Use of BRAF V600E as a molecular marker in aggressive colorectal cancer.
AB  - AIM: to compare the immunoexpression of BRAF V600E among stage of colorectal
      cancer. METHODS: this was a cross sectional, and retrospective study involving
      Dukes' stage A, B, and C colorectal carcinoma, each with 15 cases.
      Immunohistochemistry was performed in paraffin-embedded specimens of tumor mass
      for the assessment of BRAF V600E. The proportion differences of immunoexpression
      of BRAF V600E among Dukes' stage A, B, and C were tested using Chi-Square test.
      RESULTS: the result of positive BRAF V600E immunoexpression (moderately to
      strongly positive) in Dukes' stage A, B, and C were found in 1 of 15 cases, 4 of
      15 cases and 13 of 15 cases respectively. BRAF V600E immunoexpression was
      statistically significant more frequent in Dukes' stage C (p<0,001, Chi-Square
      test). CONCLUSION: positive BRAF V600E immunoexpression could be used as a marker
      of aggresive colorectal carcinoma.

PMID- 25053683
TI  - Endothelial dysfunction in the young adult: a retrospective cohort study on the
      effect of low birth weight.
AB  - AIM: to investigate the effect of low birth weight (LBW) on endothelial function,
      and to determine the role of plasma adiponectin in endothelial dysfunction by
      conducting flow mediated brachial artery (FMBA) test or vasodilation response
      (VR) and by measuring plasma asymmetrical dimethylarginine (ADMA) of young adults
      born with LBW. METHODS: in a retrospective cohort study, subjects were randomly
      selected from the growth study cohort of Tanjungsari Sumedang district West Java.
      They consisted of 67 LBW and 67 NBW (Normal Birth Weight) young adults. Dependent
      variables were plasma adiponectin, plasma ADMA, and VR. The correlation between
      plasma adiponectin and ADMA level was examined using Pearson's correlation.
      RESULTS: the relative risk for LBW to have low brachialis artery vasodilation
      response was 2.94, (95% CI:1.91-4.53), and to have low of plasma adiponectin
      concentration 1.53, (95% CI: 1.07-2.18). There was a statistically significant
      difference for all variables studied (FMBA, plasma ADMA, and plasma Adiponectin
      concentrations), while simultaneous confidence interval measurements indicated
      that the value of FMBA and the concentration of plasma adiponectin were
      significantly lower, respectively p<0.001, 95% CI: -4.409-(-2.114), and p=0.015,
      95% CI: -1.083-(-0.082) in LBW compared to NBW subjects. The correlation between
      plasma adiponectin concentration and plasma ADMA concentration in LBW subjects
      was not significant. CONCLUSION: there is an effect of LBW on endothelial
      function. LBW compared to NBW subjects have lower VR and plasma adiponectin
      concentration. There may be a small role of plasma adiponectin in endothelial
      dysfunction of young adults with LBW.

PMID- 25053684
TI  - Comparison of coronary angiography characteristics among acute coronary syndrome
      patients in young and old age patients at Cipto Mangunkusumo Hospital Jakarta.
AB  - AIM: to identify the difference between coronary angiography in patients with
      acute coronary syndrome (ACS) aged 45 years and those aged >45 years. METHODS: a
      total of 322 ACS patients who underwent coronary angiography in ICCU of Cipto
      Mangunkusumo Hospital, Jakarta between January 2008 and December 2012 were
      included in this study. The severity of coronary stenosis was determined by
      vessel score and coronary score. A significant vessel score was defined as a
      stenosis of coronary vessel of >70%. Patients were divided into two groups: those
      aged 45 years (72 cases) and those aged >45 years (250 cases). The statistical
      analysis was performed with Chi-square test for categorical data with two
      unpaired groups and the t-test or Mann-Whitney for numerical data. RESULTS: the
      highest distribution of 1-VD (single-vessel disease) patients was found the group
      of patients aged 45 years (43.1% vs 26.0%); while for 3-VD (triple-vessel
      disease) patients, the highest distribution was noticed in the group of patients
      aged >45 years (31.6% vs 18.1%). The stenosis score was lower in patients aged 45
      years compared those aged >45 years (median stenosis score 4 vs 8), p<0.001.
      Atherosclerosis was found most common for the left anterior descending artery in
      both age groups (65.3% and 74.0%). However, there was less significant stenosis
      lesion for the Left Circumflex and Right Coronary Arteries in patients aged 45.
      The result was statistically significant (26.4% and 31.9% vs 46.4% and 57.2%,
      p=0.002 and 0.001). CONCLUSION: the number of coronary artery diseases (vessel
      score) and stenosis score is lower in patients aged 45 years compared to patients
      aged >45 years.

PMID- 25053685
TI  - In-hospital major cardiovascular events between STEMI receiving thrombolysis
      therapy and primary PCI.
AB  - AIM: to compare the in-hospital major cardiovascular events between thrombolysis
      therapy and primary percutaneous coronary intervention (PCI) in patients with ST
      elevation acute myocardial infarction (STEMI. METHODS: the study design is
      retrospective cohort. Medical record of patients with STEMI onset<12 hour
      receiving thrombolysis treatment or primary PCI in Dr. Sardjito Hospital
      Yogyakarta between January 2008 and March 2010 are evaluated. The primary outcome
      is major cardiovascular events which comprise cardiovascular death, reinfarction
      and stroke during hospitalisation. The secondary outcomes are post infarction
      angina pectoris, heart failure, cardiogenic shock and bleeding. RESULTS: among 78
      patients with thrombolysis and 53 patients with primary PCI, in-hospital major
      cardiovascular events do not differ significantly (10.3% versus 9.4%; RR 1.09,
      95%CI 0.33-3.55; p=0.87). Post infarction angina pectoris is 7% versus 3.8% (RR
      2.51, 95%CI 0.50-12.60; p=0.24). The incidence of heart failure is significantly
      higher in thrombolysis (17.9% versus 5.7%; RR 3.64, 95%CI 0.99-13.38; p=0.04),
      primary PCI reduces 68.1% relative risk to develop acute heart failure in STEMI.
      The incidence of cardiogenic shock is not different. Major and minor bleeding do
      not differ significantly either. CONCLUSION: the in-hospital major cardiovascular
      events between STEMI receiving thrombolysis therapy and primary PCI is not
      significantly different. Heart failure is significantly higher in thrombolysis
      therapy and the primary PCI reduces the risk.

PMID- 25053686
TI  - Amoebic anal fistula: new insight into an old disease.
AB  - A 67-year-old gentleman underwent fistulectomy for low trans-sphincteric anal
      fistula along with curettage for an associated abscess extending proximally for
      half a centimeter into the intersphincteric plane. The roof of the cavity became
      clearly visible after satisfactory culmination of the surgical procedure.
      Histopathological examination of the fistulous tract and the curetted granulation
      tissue revealed presence of multiple trophozoites of Entamoeba histolytica
      exhibiting erythrophagocytosis in the background of mixed inflammatory
      infiltrate. This case report provides the outlook that yields the novel insight
      into the possible role of Entamoeba histolytica in the pathogenesis and
      persistence of the fistulous tract. 

PMID- 25053687
TI  - Adrenal myelolipoma, cholelithiasis and calcified spleen: retrospective diagnosis
      of sickle cell anemia using a novel triad of abdominal imaging findings.
AB  - Sickle cell anemia is an inherited abnormality of the globin chain with very high
      prevalence in the Indian subcontinent. A significant proportion of these patients
      present late in life and are at a risk of complications like acute chest syndrome
      and painful episodes till a definitive diagnosis is reached and appropriate
      treatment is started . We report a novel triad of abdominal imaging findings
      which is not reported in literature until now and which may suggest a diagnosis
      of sickle cell anemia in retrospect. Patients with this triad of abdominal
      findings should be suspected to have an underlying hemoglobinopathy and should be
      referred for further hematological workup. Although in our case the patient was
      diagnosed to have sickle cell anemia depending on the abnormal morphology of red
      cells and hemoglobin electrophoresis, it should be remembered that this triad of
      findings may be seen in other hemoglobinopathies which induce a state of chronic
      anemia. 

PMID- 25053688
TI  - Management of irritable bowel syndrome in the elderly.
AB  - Irritable bowel syndrome (IBS) is one of the most commonly encountered functional
      gastrointestinal disorders in the elderly. IBS is characterized by abdominal pain
      and altered bowel habits in the absence of specific organic pathology. The
      diagnosis of IBS usually depends primarily on established clinical criteria.
      Currently, Rome III criteria are the criteria of choice for defining IBS.
      However, aging itself is categorized as one of the alarm symptoms in the
      diagnosis of IBS that may warrant further investigation. Therefore, exclusion of
      organic diseases, using several investigations, is of paramount important in the
      older patients. In general, the treatment of IBS in the elderly is not different
      from the younger populations. However, greater caution needs to be considered
      before treating with drugs because of the altered risk-benefit profile in the
      elderly. Several studies have shown a strong relationship of IBS with psychiatric
      conditions. Thus, psychological treatments should also be considered in the
      management of IBS in the elderly. 

PMID- 25053689
TI  - Graves' dermopathy: responsive with intralesion steroid.

PMID- 25053690
TI  - Cellular cardiomyoplasty for myocardial infarction: a 2014 evidence-based update.
AB  - Myocardial infarction is one of the main cause of mortality in many countries.
      Therefore, an effective therapy for myocardial infarction is required.
      Reperfusion and other conventional therapy have been the mainstay therapy for
      myocardial infarction. However, many patients remain refractory to this therapy.
      Cellular cardiomyoplasty is considered a novel therapy, in which stem cells are
      used for cardiac repair. Stem cells are potential therapeutic approach that could
      be the ultimate solution for salvaging damaged cardiomyocyte. Based on current
      studies, stem cells are a promising therapeutic approach for myocardial
      infarction. However, some challenges need to be answered by future studies before
      this novel therapy can be widely applied. As we advance our understanding, all
      questions behind stem cell therapy would finally be revealed, and eventually
      provide the ultimate solution for ischaemic cardiac repair. This paper provide an
      overview of the latest progress in stem cell therapy for myocardial infarction. 

PMID- 25053691
TI  - National consensus on management of non-variceal upper gastrointestinal tract
      bleeding in Indonesia.
AB  - The Indonesian Society of Gastroenterology has compiled a national consensus
      guideline for the management of non-variceal upper gastrointestinal bleeding
      (NVUGIB). It is an endeavor to raise the quality of service for NVUGIB patients
      associated with peptic ulcer. The references for developing this consensus
      include three recent consensus guidelilnes on the management of NVUGIB and a
      modification of Delphi process was done to develop clinical guidelines. The three
      references are: The International Consensus Recommendations on the Management of
      Patients with Non-variceal Upper Gastrointestinal Bleeding (ICON-UGIB), 2010;
      Asia-Pacific Working Group consensus on non-variceal upper gastrointestinal
      bleeding, 2011; and Management of Patients with Ulcer Bleeding, ACG guidelines,
      2012. The consensus is compiled as a reference for Indonesian medical
      practitioners all across the country on the management of patients with non
      variceal upper gastrointestinal bleeding associated with peptic ulcer. However,
      the technical implementation extremely depends on diagnostic and therapeutical
      facilities available in each health care center. 

PMID- 25053692
TI  - Easily missed, potentially fatal complication in an extremely preterm infant.
AB  - A baby girl was delivered by emergency caesarean section at 23+6 weeks gestation
      weighing 440 g. Apgar scores were 1, 3 and 4 at 1, 5 and 10 min, respectively.
      She was intubated and transferred to the neonatal intensive care unit. Umbilical
      arterial and venous lines and an orogastric tube (OGT) were inserted. On day 4 of
      life the OGT appeared to be outside of the gastrointestinal tract on X-ray. Feeds
      were held and contrast oesophagography confirmed suspicion of an oesophageal
      perforation. She was treated with intravenous metronidazole, gentamycin and
      amoxicillin and placed nil by mouth for 10 days. Resolution of the perforation
      was confirmed on repeat contrast study (day 10) and feeds were restarted with no
      further complications.

PMID- 25053693
TI  - Malposition of pacing lead into the left ventricle: a rare complication of
      pacemaker insertion.

PMID- 25053694
TI  - Treatment of complex infantile haemangioma in a resource-poor setting.
AB  - Infantile haemangiomas affect approximately 5% of the population and usually do
      not require treatment. However, complex cutaneous haemangiomas can cause
      disabling disfigurement, while haemangiomas in the brain, airway or
      gastrointestinal tract can cause life-threatening complications. Although
      children with infantile haemangiomas are often first brought to general
      practitioners and paediatricians by parents for care, they are thought of as a
      surgical problem and usually referred to specialty care. We present a case of an
      infant from a resource-poor setting in rural Indonesia with disfiguring facial
      haemangiomas, as well as a probable airway haemangioma causing stridor at rest.
      The infant was treated with oral propranolol with marked involution of the
      cutaneous haemangioma, resolution of stridor and increase in weight. 

PMID- 25053695
TI  - Lacrosse injuries among high school boys and girls in the United States: academic
      years 2008-2009 through 2011-2012.
AB  - BACKGROUND: Lacrosse is a fast growing youth sport in the United States. Although
      there have been published studies examining injuries associated with lacrosse,
      significantly less research has been conducted in high school lacrosse players
      than in older lacrosse players. The objective of this study was to compare high
      school lacrosse injury rates and patterns by type of athletic activity (ie,
      competition vs practice) and sex. HYPOTHESIS: Lacrosse injury rates and patterns
      differ by type of athletic activity and sex. STUDY DESIGN: Descriptive
      epidemiology study. METHODS: Using the High School RIO (Reporting Information
      Online) database, lacrosse exposure and injury data were collected during 4
      academic years, 2008-2012, from a large sample of high schools in the United
      States. Schools' certified athletic trainers submitted exposure and injury
      information weekly. RESULTS: During the study period, 1406 injuries occurred
      during 716,812 athlete exposures, for an injury rate of 1.96 per 1000 athlete
      exposures (AEs). Injury rates were higher in competition than in practice (3.61
      vs 1.23 per 1000 AEs, respectively; rate ratio [RR], 2.94; 95% CI, 2.65-3.27).
      Boys had a higher injury rate than girls (2.26 vs 1.54 per 1000 AEs,
      respectively; RR, 1.47; 95% CI, 1.32-1.64). The most common injury diagnoses
      among both boys and girls were sprains/strains (boys: 35.6%; girls: 43.9%) and
      concussions (boys: 21.9%; girls: 22.7%). The most commonly injured body sites in
      competition were the head/face (32.0%), lower leg/ankle/foot (17.8%), and knee
      (12.2%), while in practice, the most commonly injured body sites were the lower
      leg/ankle/foot (34.9%), head/face (16.4%), and knee (12.7%). Among boys, the most
      common mechanisms of injury were contact with another person (40.9%) and no
      contact (21.1%). Among girls, the most common mechanisms of injury were no
      contact (26.2%), contact with a playing apparatus (24.0%), and overuse/chronic
      (17.7%). Most injured athletes (71.8%) returned to activity in <=21 days, but
      6.9% of all injuries required surgery. CONCLUSION: Lacrosse injury rates and
      patterns among high school athletes in the United States differ by type of
      athletic activity and sex. Future studies should continue to compare differences
      in injury rates and patterns in high school lacrosse, with particular emphasis
      placed on high-risk plays in competition and the prevention and management of
      concussions in both boys and girls.

PMID- 25053696
TI  - Subpectoral biceps tenodesis for the treatment of type II and IV superior labral
      anterior and posterior lesions.
AB  - BACKGROUND: Surgical repair remains the gold standard for most type II and type
      IV superior labral anterior and posterior (SLAP) lesions that fail nonoperative
      management. However, most recently, there have been data demonstrating
      unacceptably high failure rates with primary repair of type II SLAP lesions.
      Biceps tenodesis may offer an acceptable, if not better, alternative to primary
      repair of SLAP lesions. HYPOTHESIS: Subpectoral biceps tenodesis provides
      satisfactory, reproducible outcomes for the treatment of type II and type IV SLAP
      lesions. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who
      underwent subpectoral biceps tenodesis and labral debridement for type II and
      type IV SLAP lesions by a single board-certified shoulder surgeon from 2006 to
      2012 were evaluated. Exclusion criteria included those patients who underwent
      biceps tenodesis with an associated rotator cuff repair, anterior labral repair,
      or posterior labral repair. Outcome measures included the visual analog scale
      (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, and
      demographic data. RESULTS: Between 2006 and 2012, a total of 36 subpectoral
      biceps tenodesis procedures were performed in 33 patients for type II or IV SLAP
      lesions. Twenty-six patients with 29 shoulder surgeries were available for follow
      up. The average age was 46.7 years, with 16 male and 10 female patients
      participating in the study. The average follow-up was 40.17 months. There was a
      significant improvement in ASES and VAS scores: 48.1 and 6.4 preoperatively
      compared with 87.5 and 1.5 postoperatively, respectively (P < .001). There was no
      significant difference based on SLAP lesion type, patient age, or patient sex. Of
      29 shoulders, 26 (89.66%) were able to return to the previous level of activity.
      CONCLUSION: This study adds to the evolving literature supporting biceps
      tenodesis as a viable treatment for type II and IV SLAP lesions. Patient age had
      no effect on the outcomes. Based on these results, biceps tenodesis is a safe,
      effective, and technically straightforward alternative to primary SLAP repair in
      patients with type II and IV SLAP tears.

PMID- 25053697
TI  - Shape dependence of the radial distribution function of hydration water around
      proteins.
AB  - The characterization of hydration water in proteins is important to understand
      their structure, function and folding properties. A calculation of the shape
      parameters reveals considerable asymmetry in the shapes of globular proteins. The
      present study suggests a generalized approach for the calculation of radial
      distribution of hydration water by accounting for the shape asymmetry in
      proteins. The surface and radial distribution function is analyzed for three
      groups of high resolution globular proteins and nonglobular proteins. This
      generalized approach depicts a considerable difference in the hydration water
      distribution pattern around aspherical proteins as compared to the earlier method
      and this difference is more pronounced for nonglobular proteins. The peaks for
      normalized RDF are found to be sharper compared to those of bulk water. The
      normalized RDF of hydration water exactly coincides with that of the bulk beyond
      8.0 A. The radial distribution of hydration water as a function of the water
      protein distance matches with the experimentally observed distribution of
      hydration water around myoglobin. The results reveal that the distribution of
      hydration water is dependent on the shapes of proteins and hence a generalized
      approach should be used for the calculation of hydration water distribution
      around proteins, especially for nonglobular proteins. 

PMID- 25053698
TI  - Consecutive transcatheter valve-in-valve implantations: the first in the aortic
      position, the second in the mitral position, in a patient with failing aortic and
      mitral bioprostheses.
AB  - A 69-year-old man with a failing aortic valve homograft and failing mitral valve
      xenograft was admitted with an inability to complete full sentences and pulmonary
      oedema with right ventricular overload. Severe aortic and mitral regurgitation,
      severe biventricular impairment and pulmonary hypertension were confirmed on
      transthoracic and transoesophageal echocardiography. An urgent transfemoral valve
      in-valve transcatheter valve implantation (TAVI) was performed within the aortic
      valve homograft with full resolution of aortic regurgitation. Three months later,
      a semielective trans-apical valve-in-valve procedure was performed in the mitral
      position, under cardiopulmonary bypass, with full resolution of mitral
      regurgitation. His exercise tolerance increased from 5 yards to half a mile. This
      case report summarises a staged double valve-in-valve procedure in a patient who
      had three previous sternotomies and who had severe heart failure due to failing
      aortic and mitral bioprostheses. We report two different delivery approaches,
      using two different transcatheter devices, and describe valve-in-valve
      techniques, including cardiopulmonary bypass, in the catheter laboratory.

PMID- 25053699
TI  - Crescent-shaped extensive pericardial calcification.

PMID- 25053700
TI  - Evaluation of pump pulsation in respirable size-selective sampling: Part III.
      Investigation of European standard methods.
AB  - Lee et al. (Evaluation of pump pulsation in respirable size-selective sampling:
      part I. Pulsation measurements. Ann Occup Hyg 2014a;58:60-73) introduced an
      approach to measure pump pulsation (PP) using a real-world sampling train, while
      the European Standards (EN) (EN 1232-1997 and EN 12919-1999) suggest measuring PP
      using a resistor in place of the sampler. The goal of this study is to
      characterize PP according to both EN methods and to determine the relationship of
      PP between the published method (Lee et al., 2014a) and the EN methods.
      Additional test parameters were investigated to determine whether the test
      conditions suggested by the EN methods were appropriate for measuring pulsations.
      Experiments were conducted using a factorial combination of personal sampling
      pumps (six medium- and two high-volumetric flow rate pumps), back pressures (six
      medium- and seven high-flow rate pumps), resistors (two types), tubing lengths
      between a pump and resistor (60 and 90 cm), and different flow rates (2 and 2.5 l
      min(-1) for the medium- and 4.4, 10, and 11.2 l min(-1) for the high-flow rate
      pumps). The selection of sampling pumps and the ranges of back pressure were
      based on measurements obtained in the previous study (Lee et al., 2014a). Among
      six medium-flow rate pumps, only the Gilian5000 and the Apex IS conformed to the
      10% criterion specified in EN 1232-1997. Although the AirChek XR5000 exceeded the
      10% limit, the average PP (10.9%) was close to the criterion. One high-flow rate
      pump, the Legacy (PP=8.1%), conformed to the 10% criterion in EN 12919-1999,
      while the Elite12 did not (PP=18.3%). Conducting supplemental tests with
      additional test parameters beyond those used in the two subject EN standards did
      not strengthen the characterization of PPs. For the selected test conditions, a
      linear regression model [PPEN=0.014+0.375*PPNIOSH (adjusted R2=0.871)] was
      developed to determine the PP relationship between the published method (Lee et
      al., 2014a) and the EN methods. The 25% PP criterion recommended by Lee et al.
      (2014a), average value derived from repetitive measurements, corresponds to 11%
      PPEN. The 10% pass/fail criterion in the EN Standards is not based on extensive
      laboratory evaluation and would unreasonably exclude at least one pump (i.e.
      AirChek XR5000 in this study) and, therefore, the more accurate criterion of
      average 11% from repetitive measurements should be substituted. This study
      suggests that users can measure PP using either a real-world sampling train or a
      resistor setup and obtain equivalent findings by applying the model herein
      derived. The findings of this study will be delivered to the consensus committees
      to be considered when those standards, including the EN 1232-1997, EN 12919-1999,
      and ISO 13137-2013, are revised.

PMID- 25053701
TI  - A review of the effectiveness of respirators in reducing exposure to polycyclic
      aromatic hydrocarbons for coke oven workers.
AB  - OBJECTIVES: In 2011 recommendations for the prescription of lung cancer in coke
      oven workers were made in the UK. In the 1970s, a powered helmet respirator, the
      Airstream helmet, was introduced to the UK coking industry with the aim of
      reducing exposure to polycyclic aromatic hydrocarbons (PAH) aerosols and
      consequent lung cancer risks for workers on the coke oven tops. This review set
      out to identify the level of protection afforded by the Airstream helmet, when
      the helmets could be considered to have provided effective protection and whether
      the levels of protection have been maintained to the current time. METHODS: Five
      approaches were taken to identify review material, including searching the peer
      reviewed and grey literature; searching material held in the National Archive;
      using a Freedom of Information to the Health and Safety Executive; interviews
      with employees involved in the introduction of the Airstream helmet; and
      acquisition of company reports. RESULTS: The two principal companies involved in
      coke production in the UK took different approaches to the introduction of the
      Airstream helmets. Because of this, it can only be considered that effective
      wearing occurred in the industry as a whole from 1982 onwards. Exposure
      measurements made by British Steel in the late 1970s suggested that the mean
      protection factor of the Airstream helmet was ~10 (5th percentile~2.5),
      regardless of whether exposure was assessed as the inhalable aerosol or other
      measures more specific to aerosol of PAH. More recent data collected using
      biological monitoring has identified that average urinary levels of 1
      hydroxypyrene (1-HP) generally correspond with the inhalation occupational
      exposure limit for benzene soluble material. Although on occasions, relatively
      high air concentrations in-mask and urinary 1-HP concentrations have been
      identified, underlining the necessity to maintain close supervision of workers
      wearing respirators. CONCLUSIONS: Overall, we concluded that the wearing of
      helmet respirators has effectively controlled long-term average exposure to PAH
      for most workers on coke ovens since 1982.

PMID- 25053702
TI  - Graphitized silicon carbide microbeams: wafer-level, self-aligned graphene on
      silicon wafers.
AB  - Currently proven methods that are used to obtain devices with high-quality
      graphene on silicon wafers involve the transfer of graphene flakes from a growth
      substrate, resulting in fundamental limitations for large-scale device
      fabrication. Moreover, the complex three-dimensional structures of interest for
      microelectromechanical and nanoelectromechanical systems are hardly compatible
      with such transfer processes. Here, we introduce a methodology for obtaining
      thousands of microbeams, made of graphitized silicon carbide on silicon, through
      a site-selective and wafer-scale approach. A Ni-Cu alloy catalyst mediates a self
      aligned graphitization on prepatterned SiC microstructures at a temperature that
      is compatible with silicon technologies. The graphene nanocoating leads to a
      dramatically enhanced electrical conductivity, which elevates this approach to an
      ideal method for the replacement of conductive metal films in silicon carbide
      based MEMS and NEMS devices. 

PMID- 25053703
TI  - Uniform dispersion of graphene oxide in aluminum powder by direct electrostatic
      adsorption for fabrication of graphene/aluminum composites.
AB  - The excellent properties of graphene promote it as an ideal reinforcement in
      composites. However, dispersing graphene homogenously into metals is a key
      challenge that limits the development of high-performance graphene-reinforced
      metal matrix composites. Here, via simple electrostatic interaction between
      graphene oxide (GO) and Al flakes, uniform distribution of reduced graphene oxide
      (RGO) in an Al matrix is achieved. The adsorption process of GO on Al flakes is
      efficient, as it can be completed in minutes and proceeds spontaneously without
      any chemical agents. GO can be partially reduced by the electron interchange
      during the adsorption process and could be thoroughly reduced after subsequent
      thermal annealing. A densified RGO/Al composite can be obtained by hot pressing
      the RGO/Al composite powders. By employing the preceding fabrication process, a
      composite reinforced with only 0.3 wt.% of RGO shows an 18 and 17% increase in
      elastic modulus and hardness, respectively, over unreinforced Al, demonstrating
      RGO is a better reinforcement than most other reinforcements. 

PMID- 25053704
TI  - Position effect variegation and viability are both sensitive to dosage of
      constitutive heterochromatin in Drosophila.
AB  - The dosage effect of Y-chromosome heterochromatin on suppression of position
      effect variegation (PEV) has long been well-known in Drosophila. The phenotypic
      effects of increasing the overall dosage of Y heterochromatin have also been
      demonstrated; hyperploidy of the Y chromosome produces male sterility and many
      somatic defects including variegation and abnormal legs and wings. This work
      addresses whether the suppression of position effect variegation (PEV) is a
      general feature of the heterochromatin (independent of the chromosome of origin)
      and whether a hyperdosage of heterochromatin can affect viability. The results
      show that the suppression of PEV is a general feature of any type of constitutive
      heterochromatin and that the intensity of suppression depends on its amount
      instead of some mappable factor on it. We also describe a clear dosage effect of
      Y heterochromatin on the viability of otherwise wild-type embryos and the
      modification of that effect by a specific gene mutation. Together, our results
      indicate that the correct balance between heterochromatin and euchromatin is
      essential for the normal genome expression and that this balance is genetically
      controlled. 

PMID- 25053705
TI  - Comparative mapping between Coho Salmon (Oncorhynchus kisutch) and three other
      salmonids suggests a role for chromosomal rearrangements in the retention of
      duplicated regions following a whole genome duplication event.
AB  - Whole genome duplication has been implicated in evolutionary innovation and rapid
      diversification. In salmonid fishes, however, whole genome duplication
      significantly pre-dates major transitions across the family, and re
      diploidization has been a gradual process between genomes that have remained
      essentially collinear. Nevertheless, pairs of duplicated chromosome arms have
      diverged at different rates from each other, suggesting that the retention of
      duplicated regions through occasional pairing between homeologous chromosomes may
      have played an evolutionary role across species pairs. Extensive chromosomal arm
      rearrangements have been a key mechanism involved in re-dipliodization of the
      salmonid genome; therefore, we investigated their influence on degree of
      differentiation between homeologs across salmon species. We derived a linkage map
      for coho salmon and performed comparative mapping across syntenic arms within the
      genus Oncorhynchus, and with the genus Salmo, to determine the phylogenetic
      relationship between chromosome arrangements and the retention of
      undifferentiated duplicated regions. A 6596.7 cM female coho salmon map,
      comprising 30 linkage groups with 7415 and 1266 nonduplicated and duplicated
      loci, respectively, revealed uneven distribution of duplicated loci along and
      between chromosome arms. These duplicated regions were conserved across syntenic
      arms across Oncorhynchus species and were identified in metacentric chromosomes
      likely formed ancestrally to the divergence of Oncorhynchus from Salmo. These
      findings support previous studies in which observed pairings involved at least
      one metacentric chromosome. Re-diploidization in salmon may have been prevented
      or retarded by the formation of metacentric chromosomes after the whole genome
      duplication event and may explain lineage-specific innovations in salmon species
      if functional genes are found in these regions. 

PMID- 25053706
TI  - Whole-genome sequence of the C57L/J mouse inbred strain.
AB  - We sequenced the complete genome of the widely used C57L/J mouse inbred strain.
      With 40* average coverage, we compared the C57L/J sequence with that of the
      C57BL/6J and identified many known as well as novel private variants. This genome
      sequence adds another strain to the growing number of mouse inbred strains with
      complete genome sequences and is a valuable resource to the scientific community.

PMID- 25053708
TI  - The embryonic mir-35 family of microRNAs promotes multiple aspects of fecundity
      in Caenorhabditis elegans.
AB  - MicroRNAs guide many aspects of development in all metazoan species. Frequently,
      microRNAs are expressed during a specific developmental stage to perform a
      temporally defined function. The C. elegans mir-35-42 microRNAs are expressed
      abundantly in oocytes and early embryos and are essential for embryonic
      development. Here, we show that these embryonic microRNAs surprisingly also
      function to control the number of progeny produced by adult hermaphrodites. Using
      a temperature-sensitive mir-35-42 family mutant (a deletion of the mir-35-41
      cluster), we demonstrate three distinct defects in hermaphrodite fecundity. At
      permissive temperatures, a mild sperm defect partially reduces hermaphrodite
      fecundity. At restrictive temperatures, somatic gonad dysfunction combined with a
      severe sperm defect sharply reduces fecundity. Multiple lines of evidence,
      including a late embryonic temperature-sensitive period, support a role for mir
      35-41 early during development to promote subsequent sperm production in later
      larval stages. We further show that the predicted mir-35 family target sup-26
      (suppressor-26) acts downstream of mir-35-41 in this process, suggesting that sup
      26 de-repression in mir-35-41 deletion mutants may contribute to temperature
      sensitive loss of fecundity. In addition, these microRNAs play a role in male
      fertility, promoting proper morphogenesis of male-specific mating structures.
      Overall, our results demonstrate that robust activity of the mir-35-42 family
      microRNAs not only is essential for embryonic development across a range of
      temperatures but also enables the worm to subsequently develop full reproductive
      capacity. 

PMID- 25053707
TI  - Genome-wide characterization of light-regulated genes in Neurospora crassa.
AB  - The filamentous fungus Neurospora crassa responds to light in complex ways. To
      thoroughly study the transcriptional response of this organism to light, RNA-seq
      was used to analyze capped and polyadenylated mRNA prepared from mycelium grown
      for 24 hr in the dark and then exposed to light for 0 (control) 15, 60, 120, and
      240 min. More than three-quarters of all defined protein coding genes (79%) were
      expressed in these cells. The increased sensitivity of RNA-seq compared with
      previous microarray studies revealed that the RNA levels for 31% of expressed
      genes were affected two-fold or more by exposure to light. Additionally, a large
      class of mRNAs, enriched for transcripts specifying products involved in rRNA
      metabolism, showed decreased expression in response to light, indicating a
      heretofore undocumented effect of light on this pathway. Based on measured
      changes in mRNA levels, light generally increases cellular metabolism and at the
      same time causes significant oxidative stress to the organism. To deal with this
      stress, protective photopigments are made, antioxidants are produced, and genes
      involved in ribosome biogenesis are transiently repressed. 

PMID- 25053709
TI  - Molecular characterization of a heterothallic mating system in Pseudogymnoascus
      destructans, the Fungus causing white-nose syndrome of bats.
AB  - White-nose syndrome (WNS) of bats has devastated bat populations in eastern North
      America since its discovery in 2006. WNS, caused by the fungus Pseudogymnoascus
      destructans, has spread quickly in North America and has become one of the most
      severe wildlife epidemics of our time. While P. destructans is spreading rapidly
      in North America, nothing is known about the sexual capacity of this fungus. To
      gain insight into the genes involved in sexual reproduction, we characterized the
      mating-type locus (MAT) of two Pseudogymnoascus spp. that are closely related to
      P. destructans and homothallic (self-fertile). As with other homothallic
      Ascomycota, the MAT locus of these two species encodes a conserved alpha-box
      protein (MAT1-1-1) as well as two high-mobility group (HMG) box proteins (MAT1-1
      3 and MAT1-2-1). Comparisons with the MAT locus of the North American isolate of
      P. destructans (the ex-type isolate) revealed that this isolate of P. destructans
      was missing a clear homolog of the conserved HMG box protein (MAT1-2-1). These
      data prompted the discovery and molecular characterization of a heterothallic
      mating system in isolates of P. destructans from the Czech Republic. Both mating
      types of P. destructans were found to coexist within hibernacula, suggesting the
      presence of mating populations in Europe. Although populations of P. destructans
      in North America are thought to be clonal and of one mating type, the potential
      for sexual recombination indicates that continued vigilance is needed regarding
      introductions of additional isolates of this pathogen. 

PMID- 25053710
TI  - Ni3C-assisted growth of carbon nanofibres 300  degrees C by thermal CVD.
AB  - Ni-assisted thermal chemical vapor deposition (TCVD) is one of the most common
      techniques for the growth of carbon nanofibres/nanotubes (CNFs/CNTs). However,
      some fundamental issues related to the catalytic growth of CNFs/CNTs, such as the
      low-limit growth temperature, the limiting steps and the state of Ni, are still
      controversial. Here, we report the growth of CNFs at 300  degrees C; that is the
      lowest temperature for the growth of CNFs by TCVD using Ni as the catalyst so
      far. The results showed that the Ni existed in rhombohedral Ni3C, not in the
      normal form of face-centered cubic Ni, and the C atoms for building the CNFs were
      precipitated from the (001) planes of the faceted Ni3C nanoparticles. The CNFs
      are believed to be formed by the decomposition-formation cycle of metastable Ni3C
      that has a low-limit decomposition temperature of about 300  degrees C. Our
      results strongly suggest that TCVD is a valuable tool for the synthesis of
      CNFs/CNTs at temperatures below 400  degrees C, which is generally considered as
      the upper-limit temperature for fabricating complementary metal oxide
      semiconductor devices but is the low-limit temperature for growing CNFs/CNTs by
      TCVD at present. 

PMID- 25053713
TI  - Ultra-toughened nylon 12 nanocomposites reinforced with IF-WS2.
AB  - Inorganic fullerene-like WS2 nanoparticle- (IF-WS2) reinforced nylon 12
      nanocomposites have been prepared through effective ultrasonic mixing without
      using any surfactant, followed by molding at 220  degrees C. Morphological
      characterizations using scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and microcomputed tomography (micro-CT) have revealed the
      excellent dispersion of IF-WS2 nanoparticles in the nylon 12 matrix. X-ray
      diffraction (XRD) analyses have confirmed that a phase transition from alpha'
      phase to a more stable gamma-phase took place during the sintering of nylon 12,
      regardless of the amount of IF-WS2 added to the matrix. At a very low IF-WS2
      content of 2 wt%, the tensile strength and bending strength of the composites
      increased slightly by 27% and 28%, respectively. However, the toughness
      dramatically improved by 185% and 148% at IF-WS2 additions of 0.25 and 0.5 wt%,
      respectively, when compared to the neat nylon 12. It is believed that such
      improvements should mainly be attributed to the well-dispersed IF-WS2 within the
      matrix. The vastly improved toughness suggests that the resulting polymer
      nanocomposites could be promising for structural and high-performance impact
      applications. 

PMID- 25053712
TI  - AGE metabolites: a biomarker linked to cancer disparity?
AB  - Socioeconomic and environmental influences are established factors promoting
      cancer disparity, but the contribution of biologic factors is not clear. We
      report a mechanistic link between carbohydrate-derived metabolites and cancer
      that may provide a biologic consequence of established factors of cancer
      disparity. Glycation is the nonenzymatic glycosylation of carbohydrates to
      macromolecules, which produces reactive metabolites called advanced glycation end
      products (AGE). A sedentary lifestyle and poor diet all promote disease and the
      AGE accumulation pool in our bodies and also increase cancer risk. We examined
      AGE metabolites in clinical specimens of African American and European American
      patients with prostate cancer and found a higher AGE concentration in these
      specimens among African American patients when compared with European American
      patients. Elevated AGE levels corresponded with expression of the receptor for
      AGE (RAGE or AGER). We show that AGE-mediated increases in cancer-associated
      processes are dependent upon RAGE. Aberrant AGE accumulation may represent a
      metabolic susceptibility difference that contributes to cancer disparity.

PMID- 25053711
TI  - Epidemiologic and molecular prognostic review of glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive primary central
      nervous system malignancy with a median survival of 15 months. The average
      incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis
      is 64 years. Incidence is higher in men and individuals of white race and non
      Hispanic ethnicity. Many genetic and environmental factors have been studied in
      GBM, but the majority are sporadic, and no risk factor accounting for a large
      proportion of GBMs has been identified. However, several favorable clinical
      prognostic factors are identified, including younger age at diagnosis, cerebellar
      location, high performance status, and maximal tumor resection. GBMs comprise of
      primary and secondary subtypes, which evolve through different genetic pathways,
      affect patients at different ages, and have differences in outcomes. We report
      the current epidemiology of GBM with new data from the Central Brain Tumor
      Registry of the United States 2006 to 2010 as well as demonstrate and discuss
      trends in incidence and survival. We also provide a concise review on molecular
      markers in GBM that have helped distinguish biologically similar subtypes of GBM
      and have prognostic and predictive value.

PMID- 25053714
TI  - Attenuating the mortality risk of high serum uric acid: the role of physical
      activity underused.
AB  - BACKGROUND: High serum uric acid (sUA) has been associated with increased
      mortality risks, but its clinical treatment varied with potential side effects.
      The role of physical activity has received limited attention. METHODS: A cohort,
      consisting of 467 976 adults, who went through a standard health screening
      programme, with questionnaire and fasting blood samples, was successively
      recruited between 1996 and 2008. High sUA is defined as uric acid above 7.0
      mg/dL. Leisure time physical activity level was self-reported, with fully active
      defined as those with 30 min per day for at least 5 days a week. National death
      file identified 12 228 deaths with a median follow-up of 8.5 years. Cox
      proportional model was used to analyse HRs, and 12 variables were controlled,
      including medical history, life style and risk factors. FINDINGS: High sUA
      constituted one quarter of the cohort (25.6%). Their all-cause mortality was
      significantly increased [HR: 1.22 (1.15-1.29)], with much of the increase
      contributed to by the inactive (HR: 1.27 (1.17-1.37)), relative to the reference
      group with sUA level of 5-6 mg/dL. When they were fully active, mortality risks
      did not increase, but decreased by 11% (HR: 0.89 (0.82-0.97)), reflecting the
      benefits of being active was able to overcome the adverse effects of high sUA.
      Given the same high sUA, a 4-6 years difference in life expectancy was found
      between the active and the inactive. CONCLUSIONS: Physical activity is a valuable
      alternative to pharmacotherapy in its ability to reduce the increases in
      mortality risks from high sUA. By being fully active, exercise can extend life
      span by 4-6 years, a level greater than the 1-4 years of life-shortening effect
      from high sUA.

PMID- 25053715
TI  - Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6
      cooperatively promotes gastric cancer development.
AB  - OBJECTIVE: Gastric cancer (GC) is a deadly malignancy for which new therapeutic
      strategies are needed. Three transcription factors, KLF5, GATA4 and GATA6, have
      been previously reported to exhibit genomic amplification in GC. We sought to
      validate these findings, investigate how these factors function to promote GC,
      and identify potential treatment strategies for GCs harbouring these
      amplifications. DESIGN: KLF5, GATA4 and GATA6 copy number and gene expression was
      examined in multiple GC cohorts. Chromatin immunoprecipitation with DNA
      sequencing was used to identify KLF5/GATA4/GATA6 genomic binding sites in GC cell
      lines, and integrated with transcriptomics to highlight direct target genes.
      Phenotypical assays were conducted to assess the function of these factors in GC
      cell lines and xenografts in nude mice. RESULTS: KLF5, GATA4 and GATA6
      amplifications were confirmed in independent GC cohorts. Although factor
      amplifications occurred in distinct sets of GCs, they exhibited significant mRNA
      coexpression in primary GCs, consistent with KLF5/GATA4/GATA6 cross-regulation.
      Chromatin immunoprecipitation with DNA sequencing revealed a large number of
      genomic sites co-occupied by KLF5 and GATA4/GATA6, primarily located at gene
      promoters and exhibiting higher binding strengths. KLF5 physically interacted
      with GATA factors, supporting KLF5/GATA4/GATA6 cooperative regulation on co
      occupied genes. Depletion and overexpression of these factors, singly or in
      combination, reduced and promoted cancer proliferation, respectively, in vitro
      and in vivo. Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer
      development, one target gene, HNF4alpha, was also required for GC proliferation
      and could be targeted by the antidiabetic drug metformin, revealing a therapeutic
      opportunity for KLF5/GATA4/GATA6 amplified GCs. CONCLUSIONS: KLF5/GATA4/GATA6 may
      promote GC development by engaging in mutual crosstalk, collaborating to maintain
      a pro-oncogenic transcriptional regulatory network in GC cells.

PMID- 25053717
TI  - Intestinal steroidogenesis controls PPARgamma expression in the colon and is
      impaired during ulcerative colitis.
AB  - BACKGROUND AND AIMS: Immune tolerance breakdown during UC involves the peroxisome
      proliferator-activated receptor-gamma (PPARgamma), a key factor in mucosal
      homoeostasis and the therapeutic target of 5-aminosalycilates, which expression
      is impaired during UC. Here we assess the impact of glucocorticoids (GCs) on
      PPARgamma expression, focusing especially on extra-adrenal cortisol production by
      colonic epithelial cells (CECs). METHODS: Activation of PPARgamma in the colon
      was evaluated using transgenic mice for the luciferase gene under PPAR control
      (peroxisome proliferator response element-luciferase mice). Protein and mRNA
      expression of PPARgamma were evaluated with colon fragments and purified CEC from
      mice. Cortisol production and steroidogenic factor expression were quantified in
      human CEC of patients with UC and those of controls. Gene expression knockdown by
      short hairpin RNA in Caco-2 cells was used for functional studies. RESULTS: GCs
      were able to raise luciferase activity in peroxisome proliferator response
      element-luciferase mice. In the mice colons and Caco-2 cells, PPARgamma
      expression was increased either with GCs or with an inducer of steroidogenesis
      and then decreased after treatment with a steroidogenesis inhibitor. Cortisol
      production and steroidogenic factor expression, such as liver receptor homologue
      1 (LRH-1), were decreased in CEC isolated from patients with UC, directly
      correlating with PPARgamma impairment. Experiments on Caco-2 cells lacking LRH-1
      expression confirmed that LRH-1 controls PPARgamma expression by regulating GC
      synthesis in CEC. CONCLUSIONS: These results demonstrate cortisol control of
      PPARgamma expression in CEC, highlighting cortisol production deficiency in
      colonocytes as a key molecular event in the pathophysiology of UC.

PMID- 25053718
TI  - Moving towards personalised therapy in patients with hepatocellular carcinoma:
      the role of the microenvironment.
AB  - The goal of personalised therapy based on hepatocellular carcinoma (HCC)
      molecular characteristics is still beyond our grasp. Systemic treatments show
      poor efficacy, mainly because of the great heterogeneity of the tumour. Indeed,
      differences in aetiology, disease stage and biochemical composition of the
      fibrotic liver make cirrhosis itself a highly dyshomogeneous disease. Cancer
      cells grow in a cirrhotic microenvironment, interacting with stromal cells and
      engaging matrix components that differ from patient to patient, hampering the
      development of drugs to treat all patients. Growing evidence suggests a role for
      the cross-talk between HCC and the host stroma in driving disease progression and
      hence prognosis and survival. Many efforts have been devoted to identifying genes
      responsible for good or bad prognosis, but no study has yet proven helpful in
      guiding therapeutic choices and management over time, also taking into account
      the development of drug resistance. The questions of what to target and in which
      patient are still unsolved. In the personalised therapy scenario, the patient
      rather than the disease becomes the target of the therapy. However, this still
      requires an evidence-based medical approach. Herein, we will discuss how
      individual differences in terms of quality and quantity of the tissue
      microenvironment components affect progression of HCC. Then, we will highlight
      potential druggable pathways, also considering ongoing clinical trials. The
      development of biomarkers will be discussed in the light of new experimental
      research conducted with the aim of moving towards personalised therapy in
      patients with HCC. 

PMID- 25053716
TI  - Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2
      deficient mice with non-alcoholic steatohepatitis.
AB  - OBJECTIVE: Caspase-2 is an initiator caspase involved in multiple apoptotic
      pathways, particularly in response to specific intracellular stressors (eg, DNA
      damage, ER stress). We recently reported that caspase-2 was pivotal for the
      induction of cell death triggered by excessive intracellular accumulation of long
      chain fatty acids, a response known as lipoapoptosis. The liver is particularly
      susceptible to lipid-induced damage, explaining the pandemic status of non
      alcoholic fatty liver disease (NAFLD). Progression from NAFLD to non-alcoholic
      steatohepatitis (NASH) results, in part, from hepatocyte apoptosis and
      consequential paracrine-mediated fibrogenesis. We evaluated the hypothesis that
      caspase-2 promotes NASH-related cirrhosis. DESIGN: Caspase-2 was localised in
      liver biopsies from patients with NASH. Its expression was evaluated in different
      mouse models of NASH, and outcomes of diet-induced NASH were compared in wild
      type (WT) and caspase-2-deficient mice. Lipotoxicity was modelled in vitro using
      hepatocytes derived from WT and caspase-2-deficient mice. RESULTS: We showed that
      caspase-2 is integral to the pathogenesis of NASH-related cirrhosis. Caspase-2 is
      localised in injured hepatocytes and its expression was markedly upregulated in
      patients and animal models of NASH. During lipotoxic stress, caspase-2 deficiency
      reduced apoptosis, inhibited induction of profibrogenic hedgehog target genes in
      mice and blocked production of hedgehog ligands in cultured hepatocytes.
      CONCLUSIONS: These data point to a critical role for caspase-2 in lipid-induced
      hepatocyte apoptosis in vivo for the production of apoptosis-associated
      fibrogenic factors and in the progression of lipid-induced liver fibrosis. This
      raises the intriguing possibility that caspase-2 may be a promising therapeutic
      target to prevent progression to NASH.

PMID- 25053720
TI  - Developing an epidemic forecasting model for influenza a in Brisbane, Australia,
      based on climate and Hong Kong influenza a surveillance data.

PMID- 25053721
TI  - Emerging trends of HIV drug resistance in Chinese HIV-infected patients receiving
      first-line highly active antiretroviral therapy: a systematic review and meta
      analysis.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) has led to a dramatic
      decrease in AIDS-related morbidity and mortality through sustained suppression of
      human immunodeficiency virus (HIV) replication and reconstitution of the immune
      response. Settings like China that experienced rapid HAART rollout and relatively
      limited drug selection face considerable challenges in controlling HIV drug
      resistance (DR). METHODS: We conducted a systematic review and meta-analysis to
      describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected
      patients, as reflected in the point prevalence of HIV DR at key points and fixed
      intervals after treatment initiation, using data from cohort studies and cross
      sectional studies respectively. RESULTS: Pooled prevalence of HIV DR from
      longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%
      19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%-84.02%) after 72
      months of HAART. The HIV DR prevalence from cross-sectional studies was measured
      in treatment intervals; during the 0-12-month HAART treatment interval, the
      pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%-16.14%), which increased to
      22.92% at 61-72 months (95% CI, 9.45%-45.86%). Stratified analyses showed that
      patients receiving a didanosine-based regimen had higher HIV DR prevalence than
      those not taking didanosine (15.82% vs 4.97%). Patients infected through former
      plasma donation and those receiving AIDS treatment at village clinics had higher
      HIV DR prevalence than those infected through sexual transmission or treated at a
      county-level hospital. CONCLUSIONS: Our findings indicate higher prevalence of
      HIV DR for patients with longer cumulative HAART exposure, highlighting important
      subgroups for future HIV DR surveillance and control.

PMID- 25053723
TI  - Adrenomedullin and arterial stiffness: integrative approach combining monocyte
      ADM expression, plasma MR-Pro-ADM, and genome-wide association study.
AB  - BACKGROUND: Adrenomedullin (ADM) is a circulating vasoactive peptide involved in
      vascular homeostasis and endothelial function. Single nucleotide polymorphisms of
      the ADM gene are associated with blood pressure variability, and elevated levels
      of plasma midregional proadrenomedullin (MR-pro-ADM) are associated with
      cardiovascular diseases. METHODS AND RESULTS: We investigated the sources of
      variability of ADM gene expression and plasma MR-pro-ADM concentrations in the
      general population, and their relationship with markers of atherosclerosis. MR
      pro-ADM levels were assessed in 4155 individuals who underwent evaluation of
      carotid intima-media thickness and arterial rigidity (reflection index and
      stiffness index). In a subsample of 1372 individuals, ADM gene expression was
      assessed as part of a transcriptomic study of circulating monocytes. Nongenetic
      factors explained 45.8% and 7.5% of MR-pro-ADM and ADM expression variability,
      respectively. ADM expression correlated with plasma C-reactive protein,
      interleukin-receptor 1A, and myeloperoxidase, whereas MR-pro-ADM levels
      correlated with C-terminal proendothelin-1, creatinine, and N-terminal pro-B-type
      natriuretic peptide. Genome-wide association study of ADM expression and MR-pro
      ADM levels both identified a single locus encompassing the ADM gene. ADM
      expression was associated with 1 single nucleotide polymorphism rs11042717
      (P=2.36*10(-12)), whereas MR-pro-ADM was associated with 2 single nucleotide
      polymorphisms with additive effects, rs2957692 (P=1.54*10(-13)) and rs2957717
      (P=4.24*10(-8)). Reflection index was independently associated with rs11042717
      (P<10(-4)) and ADM expression (P=0.0002) but not with MR-pro-ADM. Weaker
      associations were observed for stiffness index. Intima-media thickness was not
      related to ADM single nucleotide polymorphisms or expression. CONCLUSIONS: These
      results support an involvement of the ADM gene in the modulation of peripheral
      vascular tone.

PMID- 25053724
TI  - Device-dependent association between paravalvar aortic regurgitation and outcome
      after TAVI.
AB  - OBJECTIVE: The aim of the current study was to identify predictors of
      paraprosthetic aortic regurgitation (AR) after transcatheter aortic valve
      implantation (TAVI) and examine its influence on short/medium-term mortality
      using the UK TAVI Registry. TAVI is an effective treatment for high-risk patients
      with severe symptomatic aortic stenosis (AS), but paraprosthetic AR has been
      associated with increased in-hospital and mid-term mortality. METHODS: Between
      January 2007 and December 2011, 2584 TAVI procedures were performed in the UK.
      Patients undergoing 'valve-in-valve' procedures, patients with aortic
      regurgitation as the primary pathology and with no recorded severity of AR were
      excluded from this analysis (n=144). In total, therefore, 2440 patients were
      included. Balloon-expandable and self-expanding devices were implanted in 52.7
      and 47.2%, respectively, using either transfemoral (67.7%) or non-transfemoral,
      surgical access (32.3%). RESULTS: Postprocedural AR was observed in 68%, mild AR
      in 57% and moderate-severe in 10%. A large aortic annulus, high preprocedural
      transaortic gradient, and use of self-expanding valve were independent predictors
      of moderate-severe AR. Moderate-severe (but not mild) AR was associated with
      increased mortality, and this relationship appeared significant for the balloon
      expandable but not the self-expanding device. CONCLUSIONS: Our data suggest that
      a large aortic annulus, high preprocedural transaortic gradient, and use of the
      self-expanding valve predict moderate-severe AR after TAVI. Such a degree of AR
      is associated with a significantly worse outcome with the balloon-expandable, but
      not with the self-expanding valve. Further studies are needed to verify this and
      explore potential mechanisms.

PMID- 25053725
TI  - Combining tissue repair and tissue engineering; bioactivating implantable cell
      free vascular scaffolds.
AB  - Synthetic replacement grafts for heart valves and small-diameter blood vessels
      such as coronary arteries have the potential to circumvent many of the
      limitations of currently available autologous grafting materials. Cell-free
      material incorporating biologically active compounds may guide the formation of
      fully autologous new tissue in situ derived from host cells after implantation.
      Inspiration for such bioactive compounds and their dynamics can be found in in
      vivo repair processes. Molecules such as stromal cell-derived factor 1alpha
      (SDF1alpha) that can attract progenitor cells from the bloodstream and modulate
      immune responses may be able to improve neotissue development in cell-free
      vascular and valvular grafts. Advances in the development of fully synthetic
      molecules and scaffold materials allow the spatial and temporal control of
      biologically active factors, enabling tissue engineers to mimic complex cellular
      signalling. This review focuses on combining knowledge of the molecular dynamics
      of factors involved in in vivo damage repair with the possibilities offered by
      newly developed synthetic materials. This approach has lead to encouraging
      results in the field of in situ vascular tissue engineering, and can ultimately
      lead to the development of off-the-shelf available vascular and valvular
      replacement grafts.

PMID- 25053719
TI  - Increased risk of serious bacterial infections due to maternal immunosuppression
      in HIV-exposed uninfected infants in a European country.
AB  - BACKGROUND: Morbidity and mortality are higher among human immunodeficiency virus
      (HIV) exposed but uninfected (HEU) infants than unexposed infants, particularly
      if the mother had a low CD4 count. We investigated the possible association
      between maternal immune depression during pregnancy and the risk of infection in
      HEU infants in the national French Perinatal Cohort (EPF). METHODS: All neonates,
      born alive, to HIV-1-infected women enrolled in the EPF between 2002 and 2010
      were included. The primary outcome was the first serious (hospitalization or
      death) infection during the first year of life. The main exposure variable was
      maternal CD4 cell count near delivery. The Kaplan-Meier method and multivariate
      Cox models were applied, with the different types of infections managed as
      competing events. RESULTS: Among 7638 HEU neonates, 699 had at least 1 serious
      infection (of which 159 were bacterial) with a Kaplan-Meier probability of 9.3%
      (95% confidence interval, 8.7-10.0) at 1 year. The risk of serious bacterial
      infection during the first year of life significantly increased with lower
      maternal CD4 cell count, before and after adjustment for maternal CD4 cell count
      <350 and 350-499 CD4/mm(3) (adjusted hazard ratio = 1.7 [1.2-2.6] and 1.2 [0.8
      1.9], respectively; P = .03). This association mainly concerned infections
      involving encapsulated bacteria (P = .03). The risk of serious viral infection
      was, by contrast, independent of the mother's CD4 cell count. CONCLUSIONS:
      Maternal CD4 count is significantly and specifically associated with the risk of
      serious infections with encapsulated bacteria in HEU infants.

PMID- 25053726
TI  - Myocardial amyloid infiltration: a less than expected homogeneous process.

PMID- 25053727
TI  - Diverse impacts of aging on insulin resistance in lean and obese women with
      polycystic ovary syndrome: evidence from 1345 women with the syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) represents a moving spectrum of
      hormonal to metabolic abnormalities, as women with the syndrome are aging.
      Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant
      during the early years of PCOS and fade away with the years. Metabolic
      abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle;
      however, it is unclear as to how they change, as women with the syndrome are
      aging. OBJECTIVE: To evaluate the changes in IR and its associations with
      clinical, biochemical, hormonal, and ultrasound findings in a large cohort of
      women with PCOS and controls, as they are aging. DESIGN: A cross-sectional study
      was carried out to evaluate the diverse impacts of aging on IR. SETTING: An
      outpatient clinic was chosen for the study. PARTICIPANTS: A total of 1345 women
      with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek
      ethnicity comprised the study group. MAIN OUTCOME AND MEASURES: The impact of age
      on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index,
      and several PCOS characteristics were evaluated. RESULTS: In PCOS, age (-0.045+/
      0.008) was negatively, and BMI positively (0.18+/-0.007) associated with HOMA-IR
      (R(2)=0.36). When data were stratified with regard to the BMI status, a negative
      association of age with HOMA-IR was found in lean, normal, and overweight
      patients (r: -0.266, -0.233, -0.192, P<0.001), which was neutralized in obese
      patients (r: -0.009, P: NS). Free androgen index and BMI were positively
      associated with HOMA-IR in all age quartiles. When mean HOMA-IR values were
      plotted according to BMI subgroups at different age quartiles, a significant
      gradual decrease in HOMA-IR was observed in normal (P<0.001) and overweight (P:
      0.004), but not obese, women (P: 0.202) across age quartiles. CONCLUSIONS: Aging
      increases IR in obese but not in lean and overweight women with PCOS. As BMI and
      androgens are positively associated with HOMA-IR and androgens decline through
      time, it appears that if women with PCOS do not become obese they may exhibit a
      better metabolic profile during their reproductive years.

PMID- 25053728
TI  - Fatty liver largely explains associations of subclinical hypothyroidism with
      insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis.
AB  - BACKGROUND: The association of subclinical hypothyroidism (SCH) with insulin
      resistance, metabolic syndrome (MS), and coronary atherosclerosis is uncertain.
      OBJECTIVE: To investigate the role of increased intrahepatic fat in the
      association of SCH with insulin resistance, MS, and coronary atherosclerosis.
      DESIGN, PATIENTS, AND METHODS: We conducted a cross-sectional study in a sample
      of 753 subjects (46% males) aged 35-70 years with no history of diabetes, renal,
      hepatic, thyroid, or coronary heart disease, and were participants of the
      Genetics of Atherosclerotic Disease study. SCH was defined as a high serum TSH
      level with normal free thyroxine concentration. Fatty liver (FL), coronary artery
      calcification (CAC), and abdominal visceral adipose tissue were assessed by
      computed tomography. Cross-sectional associations of SCH with and without FL,
      with MS, insulin resistance, and subclinical atherosclerosis defined as a CAC
      score >0, were examined in logistic regression models. RESULTS: SCH was observed
      in 17.7% of the population studied. The prevalence of FL was similar in both
      euthyroid and SCH subjects (31.8 vs 27.8%, P=0.371). SCH plus FL subjects were
      heavier and had more metabolic abnormalities compared with SCH plus normal liver
      subjects. In multivariate-adjusted logistic regression analyses, SCH plus FL was
      associated with MS (odds ratio (OR): 2.73, 95% CI: 1.26-5.92), insulin resistance
      (OR: 4.91, 95% CI: 1.63-14.75), and CAC score >0 (OR: 3.05, 95% CI: 1.20-7.76).
      SCH without FL showed no associations. CONCLUSION: SCH with FL is associated with
      increased odds of MS, insulin resistance, and CAC, independent of potential
      confounders.

PMID- 25053731
TI  - In reference to "The value of resident presentations at scientific meetings".

PMID- 25053732
TI  - Prognostic role of coronary flow reserve for left ventricular functional
      improvement after cardiac resynchronization therapy in patients with dilated
      cardiomyopathy.
AB  - AIMS: The aim of the study was to assess the value of coronary flow reserve (CFR)
      for predicting improvement of left ventricular function after cardiac
      resynchronization therapy (CRT). METHODS AND RESULTS: Study population included
      40 patients (mean age 58 +/- 9 years) with heart failure (ejection fraction 25, 7
      +/- 5, 4%) and QRS duration of 158 +/- 22 ms, planned for CRT. Before and after
      CRT implantation, CFR was measured non-invasively during hyperaemia induced with
      adenosine. Responders were defined by decrease in end-systolic volume >=15%.
      Follow-up echocardiography and CFR measurements were obtained after 6 months. At
      baseline there was no significant difference in left ventricular ejection
      fraction (LVEF), QRS duration, 6 min walk test distance and coronary flow
      velocity at rest between responder (n = 26) vs. non-responder group (n = 14, P =
      ns). Before CRT implantation, responders compared with non-responders, showed a
      greater increase in coronary flow velocity during hyperaemia, and consequently
      higher CFR: 2.41 +/- 0.60 vs. 1.61 +/- 0.45 (P = 0.001). There was significant
      correlation between CFR before CRT implantation and LVEF after 6 months (r =
      0.545, P = 0.001). End-diastolic, end-systolic left ventricular diameter, and CFR
      before CRT were predictors of LV functional improvement. By multivariate
      analysis, only CFR before CRT was independent predictor of left ventricular
      recovery in the follow-up period (P = 0.001). CONCLUSION: Our results demonstrate
      that preserved CFR in patients with dilated cardiomyopathy is predictive of left
      ventricular improvement after CRT implantation.

PMID- 25053733
TI  - Ecthyma gangrenosum of the cheek in a 6-month-old infant.

PMID- 25053734
TI  - Engaging children and parents in service design and delivery.
AB  - The involvement of all user groups, including children, young people (CYP) and
      their parents, encourages people to take responsibility for healthier lifestyle
      behaviours, improves treatment compliance and leads to more appropriate use of
      healthcare resources. Initiatives to engage CYP in the UK are gathering momentum,
      but significant improvements are still needed. There is a national drive from the
      department of health (DH) and NHS England, strategic clinical networks,
      operational delivery networks (including newborn networks), charities, parent
      groups and a number of other bodies to embed CYP involvement in service design
      and delivery. User engagement and patient choice, is underpinned by the NHS
      outcomes framework, and a myriad of other DH and NHS England policies and
      practice frameworks. It is now everybody's business. 

PMID- 25053735
TI  - Question 1: is the use of plastic bags for thermoregulation in term neonates
      effective in preventing hypothermia in a low-resource setting?

PMID- 25053736
TI  - Pneumonia and bronchiolitis in developing countries.

PMID- 25053737
TI  - Dientamoeba fragilis and chronic abdominal pain in children: a case-control
      study.
AB  - BACKGROUND: The association between Dientamoeba (D.) fragilis and the aetiology
      of functional gastrointestinal disorders (FGID) in children is unclear. AIM: The
      aim of this retrospective case-control study is to clarify the clinical relevance
      of D. fragilis in children with chronic abdominal pain. METHODS: From April 2011
      until April 2013, a total of 132 patients with chronic abdominal pain (AP), aged
      8-18 years, referred to a non-academic hospital, and 77 control patients, aged 8
      18 years without gastrointestinal symptoms referred to a psychiatric hospital,
      were included in the study. D. fragilis was diagnosed by real-time PCR in faecal
      samples. Symptomatic children without a D. fragilis infection fulfilled the ROME
      III criteria for AP-related FGID (AP-FGID). Clinical data were retrospectively
      analysed by examining patients' hospital records from the Jeroen Bosch Hospital
      and Herlaarhof in The Netherlands. RESULTS: D. fragilis was detected in 57
      patients with chronic AP (43.2%) and in 39 controls (50.6%) (p=0.255). No
      significant differences in symptomatology were found between D. fragilis-infected
      children and children fulfilling the criteria for AP-FGID. Parasitological
      eradication was achieved in 61.7% of patients after treatment with metronidazole
      or clioquinol, while clinical improvement occurred in only 40.4% of patients
      (p=0.435). CONCLUSIONS: There were no differences in symptoms comparing children
      with and without D fragilis infection. Furthermore, no relation was found between
      clinical and microbiological response after treatment for D. fragilis. This
      retrospective study suggests that there is no association between chronic AP and
      D. fragilis infection.

PMID- 25053738
TI  - Clinical significance of hyper-IgA in a paediatric laboratory series.
AB  - The causes of extremely elevated IgA, whether isolated or associated with an
      increase in other classes of immunoglobulin, are poorly defined in paediatrics.
      We reviewed the diagnostic significance of very high IgA levels (greater than 3
      SD above the mean for age) in a cohort of patients referred to a tertiary care
      children's hospital. Hyper-IgA was found in 91 of 6364 subjects (1.4%) and in 68
      cases was not associated with an increased IgG and/or IgM level. Most subjects
      with hyper-IgA (73.5%) had a severe immune defect, a chronic rheumatic disease or
      inflammatory bowel disease, while these conditions were very rare in a control
      group with normal IgA values (8%). Although our results may in part reflect the
      experience of a tertiary care centre, we suggest that hyper-IgA in children
      should always arouse suspicion of a serious disease. 

PMID- 25053740
TI  - The molecular epidemiology of tuberculosis in settings with a high HIV
      prevalence: implications for control.

PMID- 25053739
TI  - Transmission of tuberculosis in a South African community with a high prevalence
      of HIV infection.
AB  - BACKGROUND: In settings of high tuberculosis transmission, little is known of the
      interaction between human immunodeficiency virus (HIV) positive and HIV-negative
      tuberculosis disease and of the impact of antiretroviral treatment (ART) programs
      on tuberculosis transmission dynamics. METHODS: Mycobacterium tuberculosis
      isolates were collected from patients with tuberculosis who resided in a South
      African township with a high burden of tuberculosis and HIV infection.
      Demographic and clinical data were extracted from clinic records. Isolates
      underwent IS6110-based restriction fragment length polymorphism analysis.
      Patients with unique (nonclustered) M. tuberculosis genotypes and cluster index
      cases (ie, the first tuberculosis case in a cluster) were defined as having
      tuberculosis due to reactivation of latent M. tuberculosis infection. Secondary
      cases in clusters were defined as having tuberculosis due to recent M.
      tuberculosis infection. RESULTS: Overall, 311 M. tuberculosis genotypes were
      identified among 718 isolates from 710 patients; 224 (31%) isolates were unique
      strains, and 478 (67%) occurred in 87 clusters. Cluster index cases were
      significantly more likely than other tuberculosis cases to be HIV negative. HIV
      positive patients were more likely to be secondary cases (P = .001), including
      patients receiving ART (P = .004). Only 8% of cases of adult-adult transmission
      of tuberculosis occurred on shared residential plots. CONCLUSIONS: Recent
      infection accounted for the majority of tuberculosis cases, particularly among
      HIV-positive patients, including patients receiving ART. HIV-negative patients
      may be disproportionally responsible for ongoing transmission.

PMID- 25053742
TI  - Redox signaling via the molecular chaperone BiP protects cells against
      endoplasmic reticulum-derived oxidative stress.
AB  - Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a
      potentially significant source of cellular reactive oxygen species (ROS). Recent
      studies suggest that levels of ROS generated as a byproduct of oxidative folding
      rival those produced by mitochondrial respiration. Mechanisms that protect cells
      against oxidant accumulation within the ER have begun to be elucidated yet many
      questions still remain regarding how cells prevent oxidant-induced damage from ER
      folding events. Here we report a new role for a central well-characterized player
      in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show
      that a conserved cysteine in the lumenal chaperone BiP is susceptible to
      oxidation by peroxide, and we demonstrate that oxidation of this conserved
      cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity
      upon oxidation helps cells cope with disruption to oxidative folding within the
      ER during oxidative stress.

PMID- 25053743
TI  - Kernel methods for large-scale genomic data analysis.
AB  - Machine learning, particularly kernel methods, has been demonstrated as a
      promising new tool to tackle the challenges imposed by today's explosive data
      growth in genomics. They provide a practical and principled approach to learning
      how a large number of genetic variants are associated with complex phenotypes, to
      help reveal the complexity in the relationship between the genetic markers and
      the outcome of interest. In this review, we highlight the potential key role it
      will have in modern genomic data processing, especially with regard to
      integration with classical methods for gene prioritizing, prediction and data
      fusion. 

PMID- 25053744
TI  - Monte Carlo algorithms for Brownian phylogenetic models.
AB  - MOTIVATION: Brownian models have been introduced in phylogenetics for describing
      variation in substitution rates through time, with applications to molecular
      dating or to the comparative analysis of variation in substitution patterns among
      lineages. Thus far, however, the Monte Carlo implementations of these models have
      relied on crude approximations, in which the Brownian process is sampled only at
      the internal nodes of the phylogeny or at the midpoints along each branch, and
      the unknown trajectory between these sampled points is summarized by simple
      branchwise average substitution rates. RESULTS: A more accurate Monte Carlo
      approach is introduced, explicitly sampling a fine-grained discretization of the
      trajectory of the (potentially multivariate) Brownian process along the
      phylogeny. Generic Monte Carlo resampling algorithms are proposed for updating
      the Brownian paths along and across branches. Specific computational strategies
      are developed for efficient integration of the finite-time substitution
      probabilities across branches induced by the Brownian trajectory. The mixing
      properties and the computational complexity of the resulting Markov chain Monte
      Carlo sampler scale reasonably with the discretization level, allowing practical
      applications with up to a few hundred discretization points along the entire
      depth of the tree. The method can be generalized to other Markovian stochastic
      processes, making it possible to implement a wide range of time-dependent
      substitution models with well-controlled computational precision. AVAILABILITY:
      The program is freely available at www.phylobayes.org.

PMID- 25053741
TI  - LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and
      metastasis.
AB  - Transcriptional elongation by RNA polymerase (Pol) II is essential for gene
      expression during cell growth and differentiation. The positive transcription
      elongation factor b (P-TEFb) stimulates transcriptional elongation by
      phosphorylating Pol II and antagonizing negative elongation factors. A reservoir
      of P-TEFb is sequestered in the inactive 7SK snRNP where 7SK snRNA and the La
      related protein LARP7 are required for the integrity of this complex. Here, we
      show that P-TEFb activity is important for the epithelial-mesenchymal transition
      (EMT) and breast cancer progression. Decreased levels of LARP7 and 7SK snRNA
      redistribute P-TEFb to the transcriptionally active super elongation complex,
      resulting in P-TEFb activation and increased transcription of EMT transcription
      factors, including Slug, FOXC2, ZEB2, and Twist1, to promote breast cancer EMT,
      invasion, and metastasis. Our data provide the first demonstration that the
      transcription elongation machinery plays a key role in promoting breast cancer
      progression by directly controlling the expression of upstream EMT regulators.

PMID- 25053745
TI  - sapFinder: an R/Bioconductor package for detection of variant peptides in shotgun
      proteomics experiments.
AB  - Single nucleotide variations (SNVs) located within a reading frame can result in
      single amino acid polymorphisms (SAPs), leading to alteration of the
      corresponding amino acid sequence as well as function of a protein. Accurate
      detection of SAPs is an important issue in proteomic analysis at the experimental
      and bioinformatic level. Herein, we present sapFinder, an R software package, for
      detection of the variant peptides based on tandem mass spectrometry (MS/MS)-based
      proteomics data. This package automates the construction of variation-associated
      databases from public SNV repositories or sample-specific next-generation
      sequencing (NGS) data and the identification of SAPs through database searching,
      post-processing and generation of HTML-based report with visualized interface.
      AVAILABILITY AND IMPLEMENTATION: sapFinder is implemented as a Bioconductor
      package in R. The package and the vignette can be downloaded at
      http://bioconductor.org/packages/devel/bioc/html/sapFinder.html and are provided
      under a GPL-2 license.

PMID- 25053746
TI  - Hyperleptinemia increases the susceptibility of the cortex to generate cortical
      spreading depression.
AB  - BACKGROUND: Obesity is a risk factor for episodic migraine to develop into
      chronic migraine; hence, it is speculated that obesity and hyperleptinemia are
      associated with migraine. We hypothesized that leptin is involved in the
      mechanisms of cortical spreading depression (CSD). Therefore, we examined whether
      leptin affected a rat model of CSD to clarify the relationship between leptin and
      migraine. METHODS: We evaluated the effect of intracerebroventricular (ICV)
      administration of leptin on a rat CSD model. We then examined whether once-a-day
      intraperitoneal administration of leptin for seven days (as a chronic
      hyperleptinemia model) affected rat CSD models. Finally, we induced CSD in Zucker
      fatty (ZF) rats, which is a well-known model of obesity. RESULTS: In the parietal
      cortex, the percent change in cerebral blood flow and direct current (DC)
      potential decreased after ICV administration of leptin. A similar decrease in DC
      potential was observed in rats treated with intraperitoneal leptin. The number of
      CSDs increased significantly in rats given intraperitoneal leptin and in ZF rats.
      CONCLUSIONS: The present study suggests that leptin is involved in the mechanisms
      of CSD.

PMID- 25053747
TI  - Headache and sleep: shared pathophysiological mechanisms.
AB  - OBJECTIVE: The objective of the current article is to review the shared
      pathophysiological mechanisms which may underlie the clinical association between
      headaches and sleep disorders. BACKGROUND: The association between sleep and
      headache is well documented in terms of clinical phenotypes. Disrupted sleep-wake
      patterns appear to predispose individuals to headache attacks and increase the
      risk of chronification, while sleep is one of the longest established abortive
      strategies. In agreement, narcoleptic patients show an increased prevalence of
      migraine compared to the general population and specific familial sleep disorders
      have been identified to be comorbid with migraine with aura. CONCLUSION: The
      pathophysiology and pharmacology of headache and sleep disorders involves an
      array of neural networks which likely underlie their shared clinical association.
      While it is difficult to differentiate between cause and effect, or simply a
      spurious relationship the striking brainstem, hypothalamic and thalamic
      convergence would suggest a bidirectional influence.

PMID- 25053748
TI  - Headache, drugs and sleep.
AB  - BACKGROUND: Headache and sleep mechanisms share multiple levels of physiological
      interaction. Pharmacological treatment of headache syndromes may be associated
      with a broad range of sleep disturbances, either as a direct result of the
      pharmacology of the drug used, or by unmasking physiological alterations in sleep
      propensity seen as part of the headache symptom complex. PURPOSE: This review
      summarises known sleep and circadian effects of various drugs commonly used in
      the management of headache disorders, with particular attention paid to abnormal
      sleep function emerging as a result of treatment. METHOD: Literature searches
      were performed using MEDLINE, PubMed, and the Cochrane database using search
      terms and strings relating to generic drug names of commonly used compounds in
      the treatment of headache and their effect on sleep in humans with review of
      additional pre-clinical evidence where theoretically appropriate. CONCLUSIONS:
      Medications used to treat headache disorders may have a considerable impact on
      sleep physiology. However, greater attention is needed to characterise the
      direction of the changes of these effects on sleep, particularly to avoid
      exacerbating detrimental sleep complaints, but also to potentially capitalise on
      homeostatically useful properties of sleep which may reduce the individual burden
      of headache disorders on patients.

PMID- 25053749
TI  - Frovatriptan 2.5 mg plus dexketoprofen (25 mg or 37.5 mg) in menstrually related
      migraine. Subanalysis from a double-blind, randomized trial.
AB  - PURPOSE: The purpose of this article is to investigate the efficacy and safety of
      frovatriptan plus dexketoprofen 25 or 37.5 mg (FroDex25 or FroDex37.5,
      respectively) compared to that of frovatriptan 2.5 mg (Frova) in menstrually
      related migraine (MRM). AIM: The aim of this article is to analyze a subgroup of
      76 women who treated an MRM attack in this multicenter, randomized, double-blind,
      parallel-group study. METHODS: The primary end-point was the proportion of
      patients who were pain free (PF) at two hours. Secondary end-points included pain
      relief (PR) at two hours and 48 hours sustained pain free (SPF). RESULTS: PF
      rates at two hours were 29% under Frova, 48% under FroDex25 and 64% under
      FroDex37.5 (p < 0.05). PR at two hours was Frova 52%, FroDex25 81% and FroDex37.5
      88%, while 48 hours SPF was 18% under Frova, 30% under FroDex25 and 44% under
      FroDex37.5. CONCLUSION: Combining frovatriptan+dexketoprofen produced higher PF
      rates at two hours compared to Frova while maintaining efficacy at 48 hours.
      Tolerability profiles were comparable.

PMID- 25053750
TI  - How to classify the stylohyoid complex syndrome in the ICHD.

PMID- 25053751
TI  - Field-testing of the ICHD-3 beta diagnostic criteria for classical trigeminal
      neuralgia.
AB  - INTRODUCTION: We aimed to field-test the beta version of the third edition of the
      International Classification of Headache Disorders (ICHD-3 beta) diagnostic
      criteria for classical trigeminal neuralgia (TN). The proposed beta draft of the
      11th version of the International Classification of Diseases (ICD-11 beta) is
      almost exclusively based on the ICHD-3 beta classification structure although
      slightly abbreviated. We compared sensitivity and specificity to ICHD-2 criteria,
      and evaluated the needs for revision. METHODS: Clinical characteristics were
      systematically and prospectively collected from 206 consecutive TN patients and
      from 37 consecutive patients with persistent idiopathic facial pain in a cross
      sectional study design. RESULTS: The specificity of ICHD-3 beta was similar to
      ICHD-2 (97.3% vs. 89.2%, p = 0.248) and the sensitivity was unchanged (76.2% vs.
      74.3%, p = 0.134). The majority of false-negative diagnoses in TN patients were
      due to sensory abnormalities at clinical examination. With a proposed modified
      version of ICHD-3 beta it was possible to increase sensitivity to 96.1% (p <
      0.001 compared to ICHD-3 beta) while maintaining specificity at 83.8% (p = 0.074
      compared to ICHD-3 beta). CONCLUSION: ICHD-3 beta was not significantly different
      from ICHD-2 and both lacked sensitivity. A modification of the criteria improved
      the sensitivity greatly and is proposed for inclusion in the forthcoming ICHD-3.

PMID- 25053752
TI  - Relations between psychological avoidance, symptom severity and embarrassment in
      essential tremor.
AB  - Research with community- and clinic-based samples of essential tremor (ET)
      sufferers has identified embarrassment as a common consequence of the condition,
      leading to social anxiety and avoidance. We sought to ascertain whether
      psychological avoidance was related to embarrassment in ET, and whether any such
      relation was independent of symptom severity. Establishing whether psychological
      avoidance is related to embarrassment in ET would be a first indicator that
      mindfulness-based therapeutic approaches may be appropriate for sufferers of ET.
      Ninety-two participants were recruited through online support groups run by the
      International Tremor Foundation and the UK National Tremor Foundation, with the
      self-reported inclusion criteria being a clinical diagnosis of ET. Participants
      completed three validated questionnaires concerning ET-related embarrassment, ET
      symptom severity and psychological avoidance. Females had slightly higher
      embarrassment scores than males, and symptom severity and psychological avoidance
      made significant moderate (each accounting for 10-15% of variance approximately),
      but independent contributions to embarrassment scores. These results suggest that
      to address the potentially debilitating effects of embarrassment in ET, both
      symptom severity and psychological avoidance need to be targeted, with
      intervention research being required.

PMID- 25053753
TI  - Hering's Law Assessment Tool revisited: introducing a modified novel version-
      Patients' Response Assessment Tool after Homeopathic Treatment (PRATHoT) in
      chronic cases.
AB  - Hering's Law Assessment Tool emerged as a systematic outcome assessment tool
      following homeopathic intervention. The authors intend to modify it and develop a
      new tool-Patient Response Assessment Tool after Homeopathic Treatment (PRATHoT)
      in chronic cases through Delphi technique for systematic categorization of
      probable outcomes following individualized homeopathic treatment in chronic
      cases. The PRATHoT was drafted after literature review and iterative Delphi
      rounds with multidisciplinary expert panel, setting Fleiss kappa of 0.41 to 1.00
      a priori as the desired level of multirater agreement. Following pilot testing,
      the tool was implemented on 37 patients suffering from knee osteoarthritis over 6
      months. Logistic regression analysis confirmed that higher PRATHoT score was
      significantly associated with achieving pain visual analogue scale responses from
      the second follow-up visit onwards (B = 0.037-0.066; SE = 0.021-0.036; P = .003
      .048). The tool appeared to have acceptable psychometric properties; hence, it
      may be considered as a promising tool, amendable for further development. 

PMID- 25053754
TI  - Mindfulness-based stress reduction as a stress management intervention for
      healthy individuals: a systematic review.
AB  - Stress is a global public health problem with several negative health
      consequences, including anxiety, depression, cardiovascular disease, and suicide.
      Mindfulness-based stress reduction offers an effective way of reducing stress by
      combining mindfulness meditation and yoga in an 8-week training program. The
      purpose of this study was to look at studies from January 2009 to January 2014
      and examine whether mindfulness-based stress reduction is a potentially viable
      method for managing stress. A systematic search from Medline, CINAHL, and Alt
      HealthWatch databases was conducted for all types of quantitative articles
      involving mindfulness-based stress reduction. A total of 17 articles met the
      inclusion criteria. Of the 17 studies, 16 demonstrated positive changes in
      psychological or physiological outcomes related to anxiety and/or stress. Despite
      the limitations of not all studies using randomized controlled design, having
      smaller sample sizes, and having different outcomes, mindfulness-based stress
      reduction appears to be a promising modality for stress management. 

PMID- 25053755
TI  - Standpoints of traditional Persian physicians on geriatric nutrition.
AB  - The present article aimed to compile information on the nutritional management
      for geriatric people. Popular textbooks of Persian medicine from 10th to 18th
      century were studied to derive relative viewpoints and considerations. The
      temperament, which is defined as the combination of 4 main elements (fire, air,
      water, and soil) and 4 humors made subsequently (black bile, yellow bile, phlegm,
      and blood), changes during age periods. Imbalance in proportional amounts of
      humors in elderly should be corrected with food and medicaments having opposite
      nature to the current condition. Traditional foods included mostly well-cooked
      soups, pottages, and porridges containing fresh sheep or chicken meat. Mono
      ingredient foods were also administered according to their medical properties.
      Nutritional recommendations were also concerned with geriatrics' physiological
      conditions such as constipation, sleep disorders, and memory deficits. Many of
      traditional geriatric nutritional requirements are relevant in the present day.
      However, there are still notes that may be beneficial for consideration. 

PMID- 25053756
TI  - Insights into complex processes of animal development.

PMID- 25053757
TI  - GTP-bound Rab3A exhibits consecutive positive and negative roles during human
      sperm dense-core granule exocytosis.
AB  - Exocytosis of mammalian sperm dense-core secretory granule relies on the same
      fusion molecules as all other secretory cells; one such molecule is the small
      GTPase Rab3A. Here, we report an in-depth biochemical characterization of the
      role of Rab3A in secretion by scrutinizing the exocytotic response of
      streptolysin O-permeabilized human sperm to the acute application of a number of
      Rab3A-containing constructs and correlating the findings with those gathered with
      the endogenous protein. Full length, geranylgeranylated, and active Rab3A
      elicited human sperm exocytosis per se. With Rab3A/Rab22A chimeric proteins, we
      demonstrated that the carboxy-terminal domain of the Rab3A molecule was necessary
      and sufficient to promote exocytosis, whereas its amino-terminus prevented
      calcium-triggered secretion. Interestingly, full length Rab3A halted secretion
      when added after the docking of the acrosome to the plasma membrane. This effect
      depended on the inability of Rab3A to hydrolyze GTP. We combined modified
      immunofluorescence and acrosomal staining protocols to detect membrane fusion and
      the activation status of endogenous Rab3 simultaneously in individual cells, and
      found that GTP hydrolysis on endogenous Rab3 was mandatory for fusion pores to
      open. Our findings contribute to establishing that Rab3 modulates regulated
      exocytosis differently depending on the nucleotide bound and the exocytosis stage
      under study. 

PMID- 25053758
TI  - Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant
      infectious keratitis: a randomised clinical study.
AB  - PURPOSE: To evaluate and compare the results of bipedicle conjunctival flap (CF)
      and cryopreserved amniotic membrane graft (AMG) in the treatment of non-viral
      infectious keratitis resistant to medical treatment. METHODS: This prospective
      randomised interventional study included 40 eyes of 40 patients with resistant
      non-viral infectious keratitis. Twenty eyes received CF and 20 eyes received AMG.
      In the CF group, there were 12 eyes with fungal keratitis, 7 eyes with bacterial
      keratitis and 1 eye with Acanthamoeba keratitis. In the AMG group there were 13
      eyes with fungal keratitis, 5 eyes with bacterial keratitis and 2 eyes with
      Acanthamoeba keratitis. In the CF group, three ulcers had descemetocele and four
      ulcers were perforated. In the AMG group, four ulcers had descemetocele and two
      ulcers were perforated. In CF, 360 degrees  peritomy was done and a bipedicle CF
      from the upper conjunctiva was dissected from Tenon's capsule, mobilised to cover
      the cornea and sutured to episclera. In AMG, one or two layers of AM were trimmed
      to fit the ulcer and sutured to the cornea. The follow-up period was 6 months.
      RESULTS: Successful results were observed in 18/20 eyes (90%) in each group.
      Postoperatively, no significant differences between the two groups were found
      regarding success rate (p=1.0), epithelialisation time (p=0.75) or visual acuity
      improvement (p=0.84). CONCLUSIONS: CF and AMG are effective in treatment
      resistant infectious keratitis. They could restore ocular surface integrity and
      provide metabolic and mechanical support for corneal healing. For large corneal
      perforation, it may be better to use another procedure such as penetrating
      keratoplasty to restore ocular integrity.

PMID- 25053759
TI  - Number of excisions required to obtain clear surgical margins and prognostic
      value of AJCC T category for patients with eyelid melanoma.
AB  - AIMS: To determine the number of excisions needed to achieve clear margins and
      the prognostic value of the 7th edition of American Joint Committee on Cancer
      (AJCC) classification for eyelid melanoma. METHODS: Retrospective chart review of
      consecutive patients treated for eyelid melanoma from January 2006 through May
      2013 by the senior author at a tertiary care cancer centre. RESULTS: Of the 64
      patients (25 men and 39 women), clear surgical margins were achieved with a
      single excision in 38 patients (62%), 2 excisions in 21 patients (34%), and 3
      excisions in 2 patients (3%). Need for repeat excision was not correlated with
      the size of the surgical margin (p=0.14) or AJCC TNM classification (p=0.15).
      Nodal disease at presentation was significantly associated with T category
      greater than T2b (p=0.0026) and shorter time to disease progression (p=0.007).
      Patients followed for a minimum of 1 year with T category greater than T2b had a
      significantly higher risk of nodal or distant metastasis (p=0.0061). CONCLUSIONS:
      More than a third of patients with eyelid melanoma required more than 1 excision
      to achieve clear margins, supporting delayed reconstruction for eyelid melanoma.
      Nodal metastasis at presentation was significantly correlated with AJCC T
      category and time to progression.

PMID- 25053760
TI  - The Spaeth/Richman contrast sensitivity test (SPARCS): design, reproducibility
      and ability to identify patients with glaucoma.
AB  - AIMS: (1) To determine the ability of a novel, internet-based contrast
      sensitivity test titled the Spaeth/Richman Contrast Sensitivity Test (SPARCS) to
      identify patients with glaucoma. (2) To determine the test-retest reliability of
      SPARCS. METHODS: A prospective, cross-sectional study of patients with glaucoma
      and controls was performed. Subjects were assessed by SPARCS and the Pelli-Robson
      chart. Reliability of each test was assessed by the intraclass correlation
      coefficient and the coefficient of repeatability. Sensitivity and specificity for
      identifying glaucoma was also evaluated. RESULTS: The intraclass correlation
      coefficient for SPARCS was 0.97 and 0.98 for Pelli-Robson. The coefficient of
      repeatability for SPARCS was +/-6.7% and +/-6.4% for Pelli-Robson. SPARCS
      identified patients with glaucoma with 79% sensitivity and 93% specificity.
      CONCLUSIONS: SPARCS has high test-retest reliability. It is easily accessible via
      the internet and identifies patients with glaucoma well. TRIAL REGISTRATION:
      NCT01300949.

PMID- 25053761
TI  - Validation of a new static perimetric thresholding strategy (GATE).
AB  - AIMS: To validate the EyeSuite version of German Adaptive Threshold Estimation
      (GATE), a new thresholding algorithm for automated static perimetry. METHODS:
      Specification of agreement and its clinical evaluation as validation criteria.
      Comparison of local differential luminance sensitivity (DLS) and test time values
      between the prototype version of GATE (GATEp) and a clinical trial version,
      implemented in EyeSuite (GATEe), by means of modified Bland-Altman plots. All
      examinations were performed on the Octopus 900 perimeter (Haag-Streit Inc.,
      Koniz, Switzerland). Visually impaired patients (anterior ischaemic optic
      neuropathy [n=3], glaucomatous optic neuropathy [n=15], (post-)chiasmal visual
      pathway lesion [n=6], retinitis pigmentosa [n=6]) were either tested with grid
      30A (30 degrees  excentricity, 83 test locations) or grid 84NO (90 degrees 
      excentricity, 109 test locations, patients with RP only). RESULTS: The comparison
      of local DLS values showed good-to-acceptable agreement between GATEp and GATEe
      (bias <2 dB, limits of agreement [LOA] <5 dB) and very good repeatability for
      GATEp (bias <0.5 dB, LOA<3 dB). Median test times for GATEp and GATEe were 7.8 
      and 8.8 min for the 30 degrees  grid and 6.7  and 7.8 min for the 90 degrees 
      grid. CONCLUSIONS: GATEp and GATE, implemented in the commercially available
      EyeSuite software package (GATEe), show good agreement regarding local
      differential luminance sensitivity. GATEe can thus be also recommended for
      clinical practice. CLINICAL TRIAL NUMBER: NCT01265628.

PMID- 25053762
TI  - Three-year visual outcome of photodynamic therapy plus intravitreal bevacizumab
      with or without subtenon triamcinolone acetonide injections for polypoidal
      choroidal vasculopathy.
AB  - PURPOSE: To compare the 3-year visual outcome after double therapy of
      photodynamic therapy (PDT) with intravitreal bevacizumab (IVB) and triple therapy
      of PDT combined with IVB and subtenon triamcinolone acetonide (STTA) injections
      for polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective, comparative,
      interventional case series. METHODS: Medical records for 36 eyes in 36 patients
      (33 men, 3 women; mean age 73.5 years old; range 63-82 years old) with treatment
      naive subfoveal PCV were reviewed retrospectively. Of the 36 eyes, 17 were
      treated with double therapy and 19 with triple therapy. RESULTS: The change in
      visual acuity after triple therapy was significantly better than that after
      double therapy (p<0.05). At 36 months, improvement in visual acuity was seen in 5
      eyes (29.4%) in the double therapy group and 10 eyes (52.6%) in the triple
      therapy group. Retreatment using the initial treatment was performed for six eyes
      (35.3%) in the double therapy group and five eyes (26.3%) in the triple therapy
      group, and treatment-free period was significantly longer in the triple therapy
      group (p<0.05). The mean number of additional antivascular endothelial growth
      factor therapy was higher in the double therapy group. Post-treatment vitreous
      haemorrhage or retinal pigment epithelium tear occurred only in the double
      therapy group, in one eye (5.9%) and one eye (5.9%), respectively. CONCLUSIONS:
      Initial therapy consisting of a single session of PDT combined with IVB and STTA
      improves vision in treatment-naive subfoveal PCV. Compared with double therapy,
      this triple therapy may be more effective for PCV.

PMID- 25053764
TI  - Long-term prospective clinical follow-up after BRCA1/2 presymptomatic testing:
      BRCA2 risks higher than in adjusted retrospective studies.
AB  - BACKGROUND: The risks of breast cancer associated with BRCA1 and BRCA2 mutations
      vary considerably across studies but few have assessed prospective risks, which
      are likely to provide more reliable risk estimates for women undergoing
      presymptomatic testing. METHODS: Prospective breast cancer risks were assessed in
      254 unaffected women with BRCA1 mutations and 238 with BRCA2 mutations. Rates of
      breast cancer were calculated allowing for lead time bias and censored at time of
      risk reducing mastectomy. Degree of family history was assessed using the
      Manchester score and genotyping was undertaken using 18 single-nucleotide
      polymorphisms (SNPs) linked to breast cancer. RESULTS: Nineteen breast cancers
      occurred in women undergoing presymptomatic testing for BRCA1 and 23 for BRCA2.
      Breast cancer incidence for BRCA2 was marginally higher than BRCA1 at 20.05 per
      1000 in BRCA2 compared with 16.20 per 1000 in BRCA1. Penetrance estimates to 70
      years of age adjusted for a 6-month lead time and oophorectomy using Kaplan-Meier
      analysis were 55.1% (95% CI 36.5% to 75.6%) for BRCA1 and 71.5% (95% CI 53.2% to
      87.6%). Breast cancer cases were associated with stronger family histories and
      higher SNP aggregate scores in BRCA2. CONCLUSIONS: Prospective breast cancer
      risks in women in the UK are high especially for BRCA2 families ascertained on
      the basis of high risk. Women undergoing presymptomatic testing for BRCA2 should
      be quoted a wide range of possible breast cancer risks and should be steered
      within that range based on degree of family history, non-genetic risk factors and
      possibly SNP testing.

PMID- 25053763
TI  - Retcam fluorescein angiography findings in eyes with advanced retinoblastoma.
AB  - PURPOSE: To characterise the fluorescein angiogram (FA) findings of eyes with
      advanced retinoblastoma evaluated with the Retcam contact fundus camera. METHODS:
      A retrospective case series was performed on all new retinoblastoma patients
      evaluated with Retcam FA between 2000 and 2012. Inclusion criteria included (1)
      patients with advanced retinoblastoma (group D or E), (2) eyes studied with
      early, mid-phase and late-phase Retcam FA photographs and (3) no prior treatment.
      RESULTS: A total of 100 eyes fulfilling the inclusion criteria were identified.
      For the 47 group D eyes, FA findings included iris neovascularisation (10/47),
      large retinal vessel dilatation (46/47), small retinal vessel changes (35/47) and
      retinal venous leakage (20/47). Among the 53 group E eyes, FA findings included
      iris neovascularisation (45/53), large retinal vessel dilatation (43/53), small
      retinal vessel changes (37/53) and vascular abnormalities at multiple levels
      (11/53). CONCLUSIONS: Advanced intraocular retinoblastoma is associated with
      multiple retinal vascular abnormalities on Retcam FA. These findings may be
      helpful in defining the extent of disease and distinguishing this tumour from
      other paediatric ocular conditions. Key clinical findings were subclinical iris
      neovascularisation, a variety of small vessel changes, intrinsic tumour vessels
      and retinal venous leakage. Retcam FA was not found to be clinically useful after
      3 min.

PMID- 25053765
TI  - TRMT10A dysfunction is associated with abnormalities in glucose homeostasis,
      short stature and microcephaly.
AB  - BACKGROUND: Trm10 is a tRNA m(1)G9 methyltransferase, which in yeast modifies 12
      different tRNA species, yet is considered non-essential for viability under
      standard growth conditions. In humans, there are three Trm10 orthologs, one
      mitochondrial and two presumed cytoplasmic. A nonsense mutation in one of the
      cytoplasmic orthologs (TRMT10A) has recently been associated with microcephaly,
      intellectual disability, short stature and adolescent onset diabetes. METHODS AND
      RESULTS: The subjects were three patients who suffered from microcephaly,
      intellectual disability, short stature, delayed puberty, seizures and disturbed
      glucose metabolism, mainly hyperinsulinaemic hypoglycaemia. A homozygous
      Gly206Arg (G206R) mutation in the TRMT10A gene was identified using whole exome
      sequencing. The mutation segregated in the family and was absent from large
      control cohorts. Determination of the methylation activity of the expressed wild
      type (WT) and variant TRMT10A enzymes with transcripts of (32)P -tRNA(Gly) GCC as
      a substrate revealed a striking defect (<0.1% of WT activity) for the variant
      enzyme. The binding affinity of the G206R variant enzyme to tRNA, determined by
      fluorescence anisotropy, was similar to that of the WT enzyme. CONCLUSIONS: The
      completely abolished m(1)G9 methyltransferase activity of the mutant enzyme is
      likely due to significant defects in its ability to bind the methyl donor S
      adenosyl methionine. We propose that TRMT10A deficiency accounts for
      abnormalities in glucose homeostasis initially manifesting both ketotic and non
      ketotic hypoglycaemic events with transition to diabetes in adolescence, perhaps
      as a consequence of accelerated beta cell apoptosis. The seizure disorder and
      intellectual disability are probably secondary to mutant gene expression in
      neuronal tissue.

PMID- 25053766
TI  - Effects of a music therapy group intervention on enhancing social skills in
      children with autism.
AB  - BACKGROUND: Research indicates that music therapy can improve social behaviors
      and joint attention in children with Autism Spectrum Disorder (ASD); however,
      more research on the use of music therapy interventions for social skills is
      needed to determine the impact of group music therapy. OBJECTIVE: To examine the
      effects of a music therapy group intervention on eye gaze, joint attention, and
      communication in children with ASD. METHOD: Seventeen children, ages 6 to 9, with
      a diagnosis of ASD were randomly assigned to the music therapy group (MTG) or the
      no-music social skills group (SSG). Children participated in ten 50-minute group
      sessions over a period of 5 weeks. All group sessions were designed to target
      social skills. The Social Responsiveness Scale (SRS), the Autism Treatment
      Evaluation Checklist (ATEC), and video analysis of sessions were used to evaluate
      changes in social behavior. RESULTS: There were significant between-group
      differences for joint attention with peers and eye gaze towards persons, with
      participants in the MTG demonstrating greater gains. There were no significant
      between-group differences for initiation of communication, response to
      communication, or social withdraw/behaviors. There was a significant interaction
      between time and group for SRS scores, with improvements for the MTG but not the
      SSG. Scores on the ATEC did not differ over time between the MTG and SSG.
      CONCLUSIONS: The results of this study support further research on the use of
      music therapy group interventions for social skills in children with ASD.
      Statistical results demonstrate initial support for the use of music therapy
      social groups to develop joint attention.

PMID- 25053767
TI  - Progressive supranuclear palsy finally has a clinically measureable tau
      abnormality.

PMID- 25053768
TI  - Complexity of heart rate variability predicts outcome in intensive care unit
      admitted patients with acute stroke .
AB  - BACKGROUND: Heart rate variability (HRV) has been proposed as a predictor of
      acute stroke outcome. This study aimed to evaluate the predictive value of a
      novel non-linear method for analysis of HRV, multiscale entropy (MSE) and outcome
      of patients with acute stroke who had been admitted to the intensive care unit
      (ICU). METHODS: The MSE of HRV was analysed from 1 h continuous ECG signals in
      ICU-admitted patients with acute stroke and controls. The complexity index was
      defined as the area under the MSE curve (scale 1-20). A favourable outcome was
      defined as modified Rankin scale 0-2 at 3 months after stroke. RESULTS: The
      trends of MSE curves in patients with atrial fibrillation (AF) (n=77) were
      apparently different from those in patients with non-AF stroke (n=150) and
      controls (n=60). In addition, the values of complexity index were significantly
      lower in the patients with non-AF stroke than in the controls (25.8+/-.3 vs.
      32.3+/-4.3, p<0.001). After adjustment for clinical variables, patients without
      AF who had a favourable outcome were significantly related to higher complexity
      index values (OR=1.15, 95% CI 1.07 to 1.25, p<0.001). Importantly, the area under
      the receiver operating characteristic curve for predicting a favourable outcome
      of patients with non-AF stroke from clinical parameters was 0.858 (95% CI 0.797
      to 0.919) and significantly improved to 0.903 (95% CI 0.853 to 0.954) after
      adding on the parameter of complexity index values (p=0.020). CONCLUSIONS: In ICU
      admitted patients with acute stroke, early assessment of the complexity of HRV by
      MSE can help in predicting outcomes in patients without AF.

PMID- 25053769
TI  - Evaluation of genetic risk loci for intracranial aneurysms in sporadic
      arteriovenous malformations of the brain.
AB  - BACKGROUND: In genome-wide association studies (GWAS) five putative risk loci are
      associated with intracranial aneurysm. As brain arteriovenous malformations (AVM)
      and intracranial aneurysms are both intracranial vascular diseases and AVMs often
      have associated aneurysms, we investigated whether these loci are also associated
      with sporadic brain AVM. METHODS: We included 506 patients (168 Dutch, 338
      American) and 1548 controls, all Caucasians. Controls had been recruited as part
      of previous GWAS. Dutch patients were genotyped by KASPar assay and US patients
      by Affymetrix SNP 6.0 array. Associations in each cohort were tested by
      univariable logistic regression modelling, with subgroup analysis in 205 American
      cases with aneurysm data. Meta-analysis was performed by a Mantel-Haenszel fixed
      effect method. RESULTS: In the Dutch cohort none of the single nucleotide
      polymorphisms (SNPs) were associated with AVMs. In the American cohort, genotyped
      SNPs near SOX-17 (OR 0.74; 95% CI 0.56-0.98), RBBP8 (OR 0.76; 95% CI 0.62-0.94)
      and an imputed SNP near CDKN2B-AS1 (OR 0.79; 95% CI 0.64-0.98) were significantly
      associated with AVM. The association with SNPs near SOX-17 and CDKN2B-AS1 but not
      RBBP8 were strongest in patients with AVM with associated aneurysms. In the meta
      analysis we found no significant associations between allele frequencies and AVM
      occurrence, but rs9298506, near SOX-17 approached statistical significance (OR
      0.77; 95% CI 0.57-1.03, p=0.08). CONCLUSIONS: Our meta-analysis of two Caucasian
      cohorts did not show an association between five aneurysm-associated loci and
      sporadic brain AVM. Possible involvement of SOX-17 and RBBP8, genes involved in
      cell cycle progression, deserves further investigation.

PMID- 25053771
TI  - Patterns of cerebral and cerebellar white matter degeneration in ALS.

PMID- 25053770
TI  - Fatigue at time of CIS is an independent predictor of a subsequent diagnosis of
      multiple sclerosis.
AB  - OBJECTIVE: Fatigue is a common, disabling symptom of multiple sclerosis (MS), but
      little is known about fatigue in patients with clinically isolated syndrome
      (CIS), often the presenting symptom of MS. We aimed to investigate the prevalence
      and severity of fatigue in patients with CIS, and its association with a
      diagnosis of clinically definite MS (CDMS). METHODS: 127 patients were
      consecutively included in our ongoing prospective CIS study. At baseline,
      clinical, demographic, laboratory and MRI data were collected, and fatigue
      severity was assessed using Krupp's Fatigue Severity Scale (FSS); fatigue was
      defined as FSS>=5.0. Fatigue scores were compared with scores of 113 healthy
      controls and with scores from the literature. The association of fatigue with
      CDMS was calculated using Cox regression models. RESULTS: The mean FSS of
      patients with CIS was 4.3, similar to MS patients, and significantly higher than
      that of healthy individuals (p<0.001). Fatigue prevalence in patients with CIS
      (46.5%) was significantly higher than in controls (p<0.001). Fifty-two patients
      (40.9%) reached CDMS during follow-up. Fatigue was associated with a diagnosis of
      CDMS in univariate analysis (HR 2.6, 95% CI 1.5 to 4.6) and in multivariate
      analysis correcting for sex, age, neuroanatomical localisation of CIS, 25-OH
      vitamin D, anxiety, depression, MRI dissemination in space and gadolinium
      enhancement (HR 4.5, 95% CI 1.9 to 10.6). CONCLUSIONS: Already at the stage of
      CIS, fatigue is a very common symptom, with a severity similar to fatigue in MS
      patients. This fatigue seems unrelated to the type or severity of the attack.
      Importantly, we found that fatigue was an independent predictor of a subsequent
      diagnosis of MS.

PMID- 25053772
TI  - Neurological picture. Neurolymphomatosis as the primary presentation of non
      Hodgkin's Lymphoma.

PMID- 25053775
TI  - Proceedings of the University of Pennsylvania 6th annual conference on
      statistical issues in clinical trials: Dynamic treatment regimes.

PMID- 25053773
TI  - MRI in Leber's hereditary optic neuropathy: the relationship to multiple
      sclerosis.
AB  - BACKGROUND: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis
      (MS)-like illness appear to coexist 50 times more frequently than would be
      expected by chance. This association of LHON and MS (LMS) raises an important
      question about whether there could be a common pathophysiological mechanism
      involving mitochondrial dysfunction. OBJECTIVE: The primary aim was to define MRI
      features of LMS and LHON, and to assess the proportions of individuals displaying
      features typical of MS. Secondarily, we investigated the effect of gender on the
      risk of developing white matter lesions in the context of LHON. METHODS: A
      blinded standardised review of conventional brain MRIs of 30 patients with MS, 31
      patients with LHON and 11 patients with LMS was conducted by three independent
      experts in the field. MS-like MRI features were assessed. RESULTS: All patients
      with LMS and 26% of patients with LHON had white matter lesions. Of these, all
      patients with LMS and 25% with LHON were found to have an MRI appearance typical
      of MS. Female patients with LHON had a significantly greater risk of having white
      matter lesions consistent with MS compared with male patients (relative risk
      8.3). CONCLUSIONS: A blinded review of conventional brain MRIs shows that
      patients with LMS have a scan appearance indistinguishable from MS. Mitochondrial
      dysfunction could be a common pathophysiological pathway in the formation of
      white matter lesions. There appears to be a strong female influence on the
      radiological appearance as well as clinical development of MS in patients with
      LHON.

PMID- 25053777
TI  - University of Pennsylvania 6th annual conference on statistical issues in
      clinical trials: Dynamic treatment regimes (afternoon session).

PMID- 25053776
TI  - University of Pennsylvania 6th annual conference on statistical issues in
      clinical trials: Dynamic treatment regimes (morning session).

PMID- 25053778
TI  - Commentary on 'Elm et al'

PMID- 25053779
TI  - Science and culture: Hunting fractals in the music of J. S. Bach.

PMID- 25053782
TI  - Preshaping plates for minimally invasive fixation of calcaneal fractures using a
      real-size 3D-printed model as a preoperative and intraoperative tool.

PMID- 25053781
TI  - Featured article: induction of heme oxygenase with hemin improves pericardial
      adipocyte morphology and function in obese Zucker rats by enhancing proteins of
      regeneration.
AB  - Oxidative stress and inflammation are implicated in tissue remodeling,
      hypertrophy, and organ malfunction. Since heme-oxygenase (HO) is a cytoprotective
      enzyme with effects against oxidative stress and inflammation, we investigated
      the effects of upregulating HO with hemin on adipocyte hypertrophy, proteins of
      repair/regeneration including beta-catenin, Oct3/4 and Pax2 as well as pro
      fibrotic/remodeling proteins like osteopontin and transforming growth factor-beta
      (TGF-beta) in pericardial adipose tissue from obese Zucker rats (ZRs). Treatment
      with hemin significantly reduced pericardial adipose tissue
      inflammation/oxidative stress, suppressed osteopontin and TGF-beta, and
      attenuated pericardial adipocyte hypertrophy in obese ZRs. These were associated
      with enhanced expression of the stem/progenitor-cell marker cKit; the
      potentiation of several proteins of regeneration including beta-catenin, Oct3/4,
      Pax2; and improved pericardial adipocyte morphology. Interestingly, the
      amelioration of adipocyte hypertrophy in hemin-treated animals was accompanied by
      improved adipocyte function, evidenced by increased levels of pericardial adipose
      tissue adiponectin. Furthermore, hemin significantly reduced hypertriglyceridemia
      and hypercholesteromia in obese ZRs. The protective effects of hemin were
      accompanied by robust potentiation HO activity and the total antioxidant
      capacity, whereas the co-administration of hemin with the HO inhibitor, stannous
      mesoporphyrin abolished the effects of hemin. These data suggest that hemin
      improves pericardial adipocyte morphology and function by enhancing proteins of
      repair and regeneration, while concomitantly abating inflammatory/oxidative
      insults and suppressing extracellular-matrix/profibrotic and remodeling proteins.
      The reduction of hypertriglyceridemia, hypercholesteromia, pericardial adiposity,
      and pericardial adipocyte hypertrophy with corresponding improvement of adipocyte
      morphology/function in hemin-treated animals suggests that HO inducers may be
      explored for the design of novel remedies against cardiac complications arising
      from excessive adiposity. 

PMID- 25053783
TI  - Systems modeling of the role of interleukin-21 in the maintenance of effector
      CD4+ T cell responses during chronic Helicobacter pylori infection.
AB  - The development of gastritis during Helicobacter pylori infection is dependent on
      an activated adaptive immune response orchestrated by T helper (Th) cells.
      However, the relative contributions of the Th1 and Th17 subsets to gastritis and
      control of infection are still under investigation. To investigate the role of
      interleukin-21 (IL-21) in the gastric mucosa during H. pylori infection, we
      combined mathematical modeling of CD4(+) T cell differentiation with in vivo
      mechanistic studies. We infected IL-21-deficient and wild-type mice with H.
      pylori strain SS1 and assessed colonization, gastric inflammation, cellular
      infiltration, and cytokine profiles. Chronically H. pylori-infected IL-21
      deficient mice had higher H. pylori colonization, significantly less gastritis,
      and reduced expression of proinflammatory cytokines and chemokines compared to
      these parameters in infected wild-type littermates. These in vivo data were used
      to calibrate an H. pylori infection-dependent, CD4(+) T cell-specific
      computational model, which then described the mechanism by which IL-21 activates
      the production of interferon gamma (IFN-gamma) and IL-17 during chronic H. pylori
      infection. The model predicted activated expression of T-bet and RORgammat and
      the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in
      the modulation of IL-10. Driven by our modeling-derived predictions, we found
      reduced levels of CD4(+) splenocyte-specific tbx21 and rorc expression, reduced
      phosphorylation of STAT1 and STAT3, and an increase in CD4(+) T cell-specific IL
      10 expression in H. pylori-infected IL-21-deficient mice. Our results indicate
      that IL-21 regulates Th1 and Th17 effector responses during chronic H. pylori
      infection in a STAT1- and STAT3-dependent manner, therefore playing a major role
      controlling H. pylori infection and gastritis. Importance: Helicobacter pylori is
      the dominant member of the gastric microbiota in more than 50% of the world's
      population. H. pylori colonization has been implicated in gastritis and gastric
      cancer, as infection with H. pylori is the single most common risk factor for
      gastric cancer. Current data suggest that, in addition to bacterial virulence
      factors, the magnitude and types of immune responses influence the outcome of
      colonization and chronic infection. This study uses a combined computational and
      experimental approach to investigate how IL-21, a proinflammatory T cell-derived
      cytokine, maintains the chronic proinflammatory T cell immune response driving
      chronic gastritis during H. pylori infection. This research will also provide
      insight into a myriad of other infectious and immune disorders in which IL-21 is
      increasingly recognized to play a central role. The use of IL-21-related
      therapies may provide treatment options for individuals chronically colonized
      with H. pylori as an alternative to aggressive antibiotics.

PMID- 25053784
TI  - Propionibacterium-produced coproporphyrin III induces Staphylococcus aureus
      aggregation and biofilm formation.
AB  - The majority of bacteria detected in the nostril microbiota of most healthy
      adults belong to three genera: Propionibacterium, Corynebacterium, and
      Staphylococcus. Among these staphylococci is the medically important bacterium
      Staphylococcus aureus. Almost nothing is known about interspecies interactions
      among bacteria in the nostrils. We observed that crude extracts of cell-free
      conditioned medium from Propionibacterium spp. induce S. aureus aggregation in
      culture. Bioassay-guided fractionation implicated coproporphyrin III (CIII), the
      most abundant extracellular porphyrin produced by human-associated
      Propionibacterium spp., as a cause of S. aureus aggregation. This aggregation
      response depended on the CIII dose and occurred during early stationary-phase
      growth, and a low pH (~4 to 6) was necessary but was not sufficient for its
      induction. Additionally, CIII induced plasma-independent S. aureus biofilm
      development on an abiotic surface in multiple S. aureus strains. In strain UAMS
      1, CIII stimulation of biofilm depended on sarA, a key biofilm regulator. This
      study is one of the first demonstrations of a small-molecule-mediated interaction
      among medically relevant members of the nostril microbiota and the first
      description of a role for CIII in bacterial interspecies interactions. Our
      results indicate that CIII may be an important mediator of S. aureus aggregation
      and/or biofilm formation in the nostril or other sites inhabited by
      Propionibacterium spp. and S. aureus. Importance: Very little is known about
      interspecies interactions among the bacteria that inhabit the adult nostril,
      including Staphylococcus aureus, a potential pathogen that colonizes about a
      quarter of adults. We demonstrated that coproporphyrin III (CIII), a diffusible
      small molecule excreted by nostril- and skin-associated Propionibacterium spp.,
      induces S. aureus aggregation in a manner dependent on dose, growth phase, and
      pH. CIII also induces S. aureus to form a plasma-independent surface-attached
      biofilm. This report is the first description of a role for CIII in bacterial
      interspecies interactions at any human body site and a novel demonstration that
      nostril microbiota physiology is influenced by small-molecule-mediated
      interactions.

PMID- 25053785
TI  - Atomic force microscopy in microbiology: new structural and functional insights
      into the microbial cell surface.
AB  - Microbial cells sense and respond to their environment using their surface
      constituents. Therefore, understanding the assembly and biophysical properties of
      cell surface molecules is an important research topic. With its ability to
      observe living microbial cells at nanometer resolution and to manipulate single
      cell surface molecules, atomic force microscopy (AFM) has emerged as a powerful
      tool in microbiology. Here, we survey major breakthroughs made in cell surface
      microbiology using AFM techniques, emphasizing the most recent structural and
      functional insights. 

PMID- 25053786
TI  - vanG element insertions within a conserved chromosomal site conferring vancomycin
      resistance to Streptococcus agalactiae and Streptococcus anginosus.
AB  - Three vancomycin-resistant streptococcal strains carrying vanG elements (two
      invasive Streptococcus agalactiae isolates [GBS-NY and GBS-NM, both serotype II
      and multilocus sequence type 22] and one Streptococcus anginosus [Sa]) were
      examined. The 45,585-bp elements found within Sa and GBS-NY were nearly identical
      (together designated vanG-1) and shared near-identity over an ~15-kb overlap with
      a previously described vanG element from Enterococcus faecalis. Unexpectedly,
      vanG-1 shared much less homology with the 49,321-bp vanG-2 element from GBS-NM,
      with widely different levels (50% to 99%) of sequence identity shared among 44
      related open reading frames. Immediately adjacent to both vanG-1 and vanG-2 were
      44,670-bp and 44,680-bp integrative conjugative element (ICE)-like sequences,
      designated ICE-r, that were nearly identical in the two group B streptococcal
      (GBS) strains. The dual vanG and ICE-r elements from both GBS strains were
      inserted at the same position, between bases 1328 and 1329, within the identical
      RNA methyltransferase (rumA) genes. A GenBank search revealed that although most
      GBS strains contained insertions within this specific site, only sequence type 22
      (ST22) GBS strains contained highly related ICE-r derivatives. The vanG-1 element
      in Sa was also inserted within this position corresponding to its rumA homolog
      adjacent to an ICE-r derivative. vanG-1 insertions were previously reported
      within the same relative position in the E. faecalis rumA homolog. An ICE-r
      sequence perfectly conserved with respect to its counterpart in GBS-NY was
      apparent within the same site of the rumA homolog of a Streptococcus dysgalactiae
      subsp. equisimilis strain. Additionally, homologous vanG-like elements within the
      conserved rumA target site were evident in Roseburia intestinalis. Importance:
      These three streptococcal strains represent the first known vancomycin-resistant
      strains of their species. The collective observations made from these strains
      reveal a specific hot spot for insertional elements that is conserved between
      streptococci and different Gram-positive species. The two GBS strains potentially
      represent a GBS lineage that is predisposed to insertion of vanG elements.

PMID- 25053787
TI  - Detection of the Middle East respiratory syndrome coronavirus genome in an air
      sample originating from a camel barn owned by an infected patient.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel
      betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and
      causing severe respiratory infections in humans. While bats were suggested to be
      involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is
      uncertain. On the other hand, serological and virological data suggest dromedary
      camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS
      CoV from a camel and its infected owner and provided evidence for the direct
      transmission of MERS-CoV from the infected camel to the patient. Here, we extend
      this work and show that identical MERS-CoV RNA fragments were detected in an air
      sample collected from the same barn that sheltered the infected camel in our
      previous study. These data indicate that the virus was circulating in this farm
      concurrently with its detection in the camel and in the patient, which warrants
      further investigations for the possible airborne transmission of MERS-CoV.
      Importance: This work clearly highlights the importance of continuous
      surveillance and infection control measures to control the global public threat
      of MERS-CoV. While current MERS-CoV transmission appears to be limited, we advise
      minimal contact with camels, especially for immunocompromised individuals, and
      the use of appropriate health, safety, and infection prevention and control
      measures when dealing with infected patients. Also, detailed clinical histories
      of any MERS-CoV cases with epidemiological and laboratory investigations carried
      out for any animal exposure must be considered to identify any animal source.

PMID- 25053788
TI  - Shielding of a lipooligosaccharide IgM epitope allows evasion of neutrophil
      mediated killing of an invasive strain of nontypeable Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae is a frequent cause of noninvasive mucosal
      inflammatory diseases but may also cause invasive diseases, such as sepsis and
      meningitis, especially in children and the elderly. Infection by nontypeable
      Haemophilus influenzae is characterized by recruitment of neutrophilic
      granulocytes. Despite the presence of a large number of neutrophils, infections
      with nontypeable Haemophilus influenzae are often not cleared effectively by the
      antimicrobial activity of these immune cells. Herein, we examined how nontypeable
      Haemophilus influenzae evades neutrophil-mediated killing. Transposon sequencing
      (Tn-seq) was used on an isolate resistant to neutrophil-mediated killing to
      identify genes required for its survival in the presence of human neutrophils and
      serum, which provided a source of complement and antibodies. Results show that
      nontypeable Haemophilus influenzae prevents complement-dependent neutrophil
      mediated killing by expression of surface galactose-containing oligosaccharide
      structures. These outer-core structures block recognition of an inner-core
      lipooligosaccharide epitope containing glucose attached to heptose HepIII-beta1,2
      Glc by replacement with galactose attached to HepIII or through shielding HepIII
      beta1,2-Glc by phase-variable attachment of oligosaccharide chain extensions.
      When the HepIII-beta1,2-Glc-containing epitope is expressed and exposed,
      nontypeable Haemophilus influenzae is opsonized by naturally acquired IgM
      generally present in human serum and subsequently phagocytosed and killed by
      human neutrophils. Clinical nontypeable Haemophilus influenzae isolates
      containing galactose attached to HepIII that are not recognized by this IgM are
      more often found to cause invasive infections. Importance: Neutrophils are white
      blood cells that specialize in killing pathogens and are recruited to sites of
      inflammation. However, despite the presence of large numbers of neutrophils in
      the middle ear cavity and lungs of patients with otitis media or chronic
      obstructive pulmonary disease, respectively, the bacterium nontypeable
      Haemophilus influenzae is often not effectively cleared from these locations by
      these immune cells. In order to understand how nontypeable Haemophilus influenzae
      is able to cause inflammatory diseases in the presence of neutrophils, we
      determined the mechanism that underlies resistance to neutrophil-mediated
      killing. We have shown that nontypeable Haemophilus influenzae prevents binding
      of antibodies of the IgM subtype through changes in their surface
      lipooligosaccharide structure, thereby preventing complement activation and
      clearance by human neutrophils.

PMID- 25053791
TI  - Acute compartment syndrome after medial gastrocnemius tear.
AB  - Acute compartment syndrome after medial gastrocnemius tear is very rare. It can
      involve the superficial posterior compartment alone or progress to involve all
      the 4 compartments of the lower legs. Those patients with high pain tolerance and
      minor trauma can lead to delayed presentation. Immediate fasciotomy is the
      treatment of choice. LEVELS OF EVIDENCE: Therapeutic Level IV, Case Study.

PMID- 25053789
TI  - Parallel evolution of Streptococcus pneumoniae and Streptococcus mitis to
      pathogenic and mutualistic lifestyles.
AB  - The bacterium Streptococcus pneumoniae is one of the leading causes of fatal
      infections affecting humans. Intriguingly, phylogenetic analysis shows that the
      species constitutes one evolutionary lineage in a cluster of the otherwise
      commensal Streptococcus mitis strains, with which humans live in harmony. In a
      comparative analysis of 35 genomes, including phylogenetic analyses of all
      predicted genes, we have shown that the pathogenic pneumococcus has evolved into
      a master of genomic flexibility while lineages that evolved into the
      nonpathogenic S. mitis secured harmonious coexistence with their host by
      stabilizing an approximately 15%-reduced genome devoid of many virulence genes.
      Our data further provide evidence that interspecies gene transfer between S.
      pneumoniae and S. mitis occurs in a unidirectional manner, i.e., from S. mitis to
      S. pneumoniae. Import of genes from S. mitis and other mitis, anginosus, and
      salivarius group streptococci ensured allelic replacements and antigenic
      diversification and has been driving the evolution of the remarkable structural
      diversity of capsular polysaccharides of S. pneumoniae. Our study explains how
      the unique structural diversity of the pneumococcal capsule emerged and
      conceivably will continue to increase and reveals a striking example of the
      fragile border between the commensal and pathogenic lifestyles. While genomic
      plasticity enabling quick adaptation to environmental stress is a necessity for
      the pathogenic streptococci, the commensal lifestyle benefits from stability.
      Importance: One of the leading causes of fatal infections affecting humans,
      Streptococcus pneumoniae, and the commensal Streptococcus mitis are closely
      related obligate symbionts associated with hominids. Faced with a shortage of
      accessible hosts, the two opposing lifestyles evolved in parallel. We have shown
      that the nonpathogenic S. mitis secured harmonious coexistence with its host by
      stabilizing a reduced genome devoid of many virulence genes. Meanwhile, the
      pathogenic pneumococcus evolved into a master of genomic flexibility and imports
      genes from S. mitis and other related streptococci. This process ensured
      antigenic diversification and has been driving the evolution of the remarkable
      structural diversity of capsular polysaccharides of S. pneumoniae, which
      conceivably will continue to increase and present a challenge to disease
      prevention.

PMID- 25053792
TI  - Balancing the risk of complications in foot and ankle surgical patients taking
      antithrombotic medication.
AB  - This review intends to provide guidance regarding perioperative management of
      anticoagulation and antiplatelet drug therapy as they relate to foot and ankle
      surgery. Venous and arterial thromboembolism are conditions in which the blood
      clots inappropriately, causing considerable morbidity and mortality. With an
      increase in awareness of thromboembolic risk factors and expansion of therapeutic
      options, more patients are routinely taking antithrombotic medication. When these
      patients require invasive procedures, a decision needs to be made if
      antithrombotic medication should be held perioperatively and if additional
      precautions are needed in the interim. Understanding the factors affecting the
      management of thromboembolism during the perioperative period can reduce the
      potential for complications. LEVELS OF EVIDENCE: Therapeutic, Level V: Expert
      opinion.

PMID- 25053793
TI  - Crossed-screws provide greater tarsometatarsal fusion stability compared to
      compression plates.
AB  - BACKGROUND: Hallux valgus is a common deformity that is often treated with a
      fusion of the first tarsometatarsal (TMT) joint. Crossed-screws are currently the
      accepted standard but advances in plate systems present opportunities for
      improved clinical outcomes; however, in vitro testing should be performed prior
      to clinical implementation. The purpose of this study was to determine whether a
      locking plate with surgeon-mediated compression provides similar fusion stability
      compared to crossed-screws and if bone density or joint size are related to
      construct success. METHODS: Ten matched-pair cadaveric specimens received first
      TMT fusions with either crossed-screws or a compression plate and were loaded for
      1000 cycles to assess the amount of joint motion measured as plantar gapping.
      Bone density was quantified using computed tomography images of each specimen,
      and joint height was measured with calipers. RESULTS: Crossed-screws provided 3
      times greater resistance to plantar gapping compared to compression plates after
      1000 cycles. Bone density and joint size did not affect resistance to plantar
      gapping for either construct. CONCLUSION: Lag screws or a plantarly applied plate
      are needed to maximize TMT fusion stability prior to osseous union. Dorsomedially
      applied plates are also effective when paired with a lag screw placed across the
      TMT joint. These constructs do not appear to depend on bone density or joint
      size, suggesting that patients with osteoporosis are viable candidates. CLINICAL
      RELEVANCE: The results of this study suggest that traditional, lagged cross
      screws provide greater stability to that of a dorsally place compression plate
      and may lead to better rates of union. LEVELS OF EVIDENCE: Therapeutic, Level V:
      Cadaveric Study.

PMID- 25053794
TI  - The effects of a semi-rigid brace or taping on talocrural and subtalar kinematics
      in chronic ankle instability.
AB  - BACKGROUND: A semi-rigid brace or taping is often used to prevent giving-ways in
      the joint with chronic ankle instability (CAI). However, it remains unknown
      whether the application of a semi-rigid brace or taping modifies abnormal
      kinematics in CAI joints. The objective of this study was to determine if the
      application of a semi-rigid brace or taping of the ankle normalizes abnormal
      weight-bearing kinematics in CAI joints during ankle internal rotation in plantar
      flexion. METHODS: A total of 14 male patients with unilateral CAI (mean age 21.1
      +/- 2.5 years) were enrolled. Three-dimensional bone models created from the
      computed tomography images were matched to the fluoroscopic images to compute the
      6 degrees-of-freedom talocrural, subtalar, and ankle joint complex (AJC)
      kinematics for the healthy and contralateral CAI joints, as well as for CAI
      joints with a brace or taping. Selected outcome measures were talocrural anterior
      translation, talocrural internal rotation, and subtalar internal rotation.
      RESULTS: There was no significant difference in talocrural anterior translation
      and internal rotation induced by applying either a semi-rigid brace or taping (P
      > .05). For subtalar internal rotation, there was a tendency toward restoration
      of normal kinematics in CAI joints after applying a semi-rigid brace or taping.
      However, the difference was not significant (P > .05). DISCUSSION: Application of
      a semi-rigid brace or taping had limited effects on the CAI joint during weight
      bearing ankle internal rotation in plantar flexion. Further studies using a
      variety of testing conditions should be conducted in the future. LEVELS OF
      EVIDENCE: Therapeutic, Level IV: Cross-Sectional Case Series.

PMID- 25053795
TI  - Materialistic Desires or Childhood Adversities as Explanations for Girls' Trading
      Sex for Benefits.
AB  - This study investigates whether high school and younger South Korean girls trade
      sex with middle-aged men for benefits due to cultural emphasis on
      materialism/consumerism, childhood adversities, or both. This form of
      prostitution, referred to as "compensated dating," is common in economically
      developed East Asian Countries, where there is debate about its causes.
      Purposeful sampling was used to select a diverse group of 25 girls who described
      involvement in compensated dating, and a life calendar method was used to guide
      the interview. The rich data were subjected to thematic analysis to show the
      nature of prostitution involvement, precursors, and motivations. Data analysis
      revealed that sole reliance on materialistic desire as an explanation of
      prostitution obscures the influence of peer pressure and family dysfunction.
      Findings suggest the need for social services rather than punitive responses to
      girls involved in compensated dating. 

PMID- 25053797
TI  - Genotypically defined beta-lactamase-negative ampicillin-resistant isolates of
      non-typable Haemophilus influenzae are associated with increased invasion of
      bronchial epithelial cells in vitro.
AB  - The aim of the study was to investigate the association between the presence of
      altered penicillin-binding protein 3 (PBP3) in non-typable Haemophilus influenzae
      (NTHi) and an increased capacity to invade bronchial epithelial cells in vitro. A
      collection of 40 clinical isolates of NTHi comprised of 20 with normal PBP3 and
      20 with altered PBP3 (defined by an N526K substitution) was established. The
      isolates were tested for the ability to invade bronchial epithelial cells in
      vitro using a 4 h gentamicin survival assay. Invasion was measured as the
      percentage of intracellular organisms relative to the initial inoculum. The mean
      invasion rate was 0.00-14.79 % in the normal PBP3 isolates and 0.02-36.69 % in
      the altered PBP3 isolates. The altered PBP3 isolates had a higher (P = 0.003)
      mean invasion rate (6.86 %, n = 20) than the normal PBP3 isolates (1.31 %, n =
      20). Subsequently, two variants of altered PBP3 (transformant 1, N526K;
      transformant 2, M377I, S385T, L389F and N526K) were cloned into three of the
      initial isolates (parents) with normal PBP3 and relatively low invasive ability,
      and the parents and transformants tested for invasion as above. There was no
      difference (P = 0.89) in the mean invasion rates for the parents (0.81 %, n = 3),
      transformants 1 (0.90 %, n = 3) and transformants 2 (1.38 %, n = 3). There was an
      association between the presence of altered PBP3 in NTHi and an increased
      capacity to invade BEAS-2B cells in vitro, but cloning experiments suggested that
      the altered PBP3 was not involved directly in enhanced invasion.

PMID- 25053796
TI  - Molecular epidemiology of enterovirus 71 strains isolated from children in
      Yamagata, Japan, between 1990 and 2013.
AB  - Enterovirus 71 infections have become a major public issue in the Asia-Pacific
      region due to the large number of fatal cases. To clarify the longitudinal
      molecular epidemiology of enterovirus 71 (EV71) in a community, we isolated 240
      strains from children, mainly with hand-foot-and-mouth diseases, between 1990 and
      2013 in Yamagata, Japan. We carried out a sequence analysis of the VP1 region
      (891 bp) using 223 isolates and identified six subgenogroups (B2, B4, B5, C1, C2
      and C4) during the study period. Subgenogroups C1 and B2 were found only between
      1990 and 1993 and have not reappeared since. In contrast, strains in
      subgenogroups C2, C4 and B5 appeared repeatedly with genomic variations. Recent
      reports from several local communities in Japan have suggested that identical
      predominant subgenogroup strains, which have also been found in the Asia-Pacific
      region, have been circulating in a wide area in Japan. However, it is likely that
      there is a discrepancy between the major subgenogroups circulating in the Asia
      Pacific region and those in Europe. It is necessary to continue the analysis of
      the longitudinal epidemiology of EV71 in local communities, as well as on
      regional and global levels, to develop strategies against severe EV71 infections.

PMID- 25053798
TI  - Macrolide- and tetracycline-resistance determinants of colonizing group B
      streptococcus in women in Egypt.
AB  - Group B streptococcus (GBS) is a commensal bacterium of the human
      gastrointestinal and genital tracts. It is a leading cause of neonatal sepsis and
      meningitis, and has also been recognized as an important pathogen in pregnant
      women and the elderly. We investigated mechanisms of macrolide and tetracycline
      resistance in GBS colonizing women in Egypt. A total of 100 isolates were
      screened using standard antibiotic susceptibility tests. A multiplex PCR assay
      was used to detect macrolide- and tetracycline-resistance determinants. All
      isolates were uniformly susceptible to penicillin G, ampicillin, cefotaxime,
      vancomycin and levofloxacin. The resistance rates to erythromycin, clindamycin,
      azithromycin, tetracycline and chloramphenicol were 17, 14, 16, 98 and 1 %,
      respectively. Among the erythromycin-resistant isolates, 82.4 % had constitutive
      macrolide-lincosamide-streptogramin B (cMLSB) resistance, 5.9 % had inducible
      MLSB (iMLSB) resistance and 11.8 % had M phenotype resistance. Among the cMLSB
      phenotypes, 64.3 % of isolates harboured the ermB gene and 35.7 % of isolates
      harboured none of the investigated macrolide-resistance genes. The single strain
      expressing the iMLSB phenotype possessed the ermA gene. Of the two strains with
      the M phenotype, only one possessed the mefA/E gene. Conversely, seven macrolide
      sensitive strains (MIC <0.03 ug ml(-1)) were ermB positive and one macrolide
      sensitive strain (MIC <0.03 ug ml(-1)) harboured mefA/E. Tetracycline resistance
      was predominantly due to tetM, which was detected alone (83.7 %) or in
      association with tetL (12.2 %), tetK (1 %) or tetO (1 %). One strain carried tetM
      associated with both tetL and tetK, and another strain carried tetO alone. The
      tetO strains were positive for the mefA/E gene, and the tetL and tetK carrier
      strains harboured the ermB gene. Susceptible strains harbouring but not
      expressing an antibiotic-resistance gene should be regarded as potentially
      resistant. These results emphasize the need to monitor the epidemiology of GBS
      antibiotic resistance in Egypt.

PMID- 25053799
TI  - Dormant bacteria within Staphylococcus epidermidis biofilms have low inflammatory
      properties and maintain tolerance to vancomycin and penicillin after entering
      planktonic growth.
AB  - Staphylococcus epidermidis is the most commonly isolated aetiological agent of
      nosocomial infections, mainly due to its ability to establish biofilms on
      indwelling medical devices. Detachment of bacteria from S. epidermidis biofilms
      and subsequent growth in the planktonic form is a hallmark of the pathogenesis of
      these infections leading to dissemination. Here we showed that S. epidermidis
      cells collected from biofilms cultured in conditions that promote cell viability
      present marked changes in their physiological status upon initiating a planktonic
      mode of growth. When compared to cells growing in biofilms, they displayed an
      increased SYBR green I staining intensity, increased transcription of the rpiA
      gene, decreased transcription of the icaA gene, as well as higher susceptibility
      to vancomycin and penicillin. When bacteria collected from biofilms with high
      proportions of dormant cells were subsequently cultured in the planktonic mode, a
      large proportion of cells maintained a low SYBR green I staining intensity and
      increased resistance to vancomycin and penicillin, a profile typical of dormant
      cells. This phenotype further associated with a decreased ability of these
      biofilm-derived cells to induce the production of pro-inflammatory cytokines by
      bone marrow-derived dendritic cells in vitro. These results demonstrated that
      cells detached from the biofilm maintain a dormant cell-like phenotype, having a
      low pro-inflammatory effect and decreased susceptibility to antibiotics,
      suggesting these cells may contribute to the recalcitrant nature of biofilm
      infections.

PMID- 25053800
TI  - Renal function, acute kidney injury and hospital mortality in patients with acute
      myocardial infarction.
AB  - OBJECTIVES: To examine retrospectively the relationship between acute kidney
      injury (AKI) and acute myocardial infarction (AMI), and the association between
      estimated glomerular filtration rate (eGFR) at admission and AKI outcome.
      METHODS: AKI was defined as an increase in serum creatinine (SCr) by >= 0.3 mg/dl
      within 48 h or an increase in SCr to >= 1.5 times baseline within the first 7
      days of hospitalization. Patients with AMI were divided into subgroups according
      to their eGFR at admission and the development of AKI. RESULTS: This study
      enrolled 396 patients with AMI; 48 (12.1%) developed AKI. In-hospital mortality
      was 39.6% (19/48) for patients with AKI compared with 7.5% (26/348) in those
      without AKI (odds ratio [OR] 8.11; 95% confidence interval [CI] 4.02, 16.39). The
      mortality rate was 35.7% (five of 14) in the eGFR >= 60 ml/min/1.73 m(2) with AKI
      group (OR 6.21, 95% CI 1.50, 25.69) and 41.2% (14/34) in the eGFR <60 ml/min/1.73
      m(2) with AKI group (OR 12.62, 95% CI 5.54, 28.74). CONCLUSIONS: AKI development
      was common and associated with mortality in AMI patients with either preserved or
      impaired eGFR levels.

PMID- 25053801
TI  - Metabolic syndrome, adiponectin and proinflammatory status in patients with type
      1 diabetes mellitus.
AB  - OBJECTIVES: To assess the prevalence of metabolic syndrome and evaluate
      proinflammatory status in patients with type 1 diabetes, and to analyse the
      relationship between inflammation, metabolic control and insulin resistance in
      these patients. METHODS: Patients with type 1 diabetes were stratified according
      to the presence or absence of metabolic syndrome. Serum adiponectin, leptin,
      tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and high-sensitivity C
      reactive protein (hsCRP) were quantified. RESULTS: The prevalence of metabolic
      syndrome was 28.6% (22/77). Patients with metabolic syndrome had lower
      adiponectin concentrations and higher leptin, TNF-alpha, IL-6 and hsCRP
      concentrations compared with patients without metabolic syndrome. In addition,
      metabolic syndrome was associated with higher glycosylated haemoglobin and
      insulin dose, and increased insulin resistance. CONCLUSIONS: The proinflammatory
      state associated with metabolic syndrome in patients with type 1 diabetes leads
      to deterioration of glycaemic control and an increase in the required daily dose
      of insulin. Early and proactive diagnosis of metabolic syndrome in these patients
      will allow medication and lifestyle optimization, in order to prevent the
      occurrence of diabetes complications and improve health-related quality-of-life.

PMID- 25053802
TI  - Cognition and health in African American men.
AB  - OBJECTIVE: Despite high rates of poor health outcomes, little attention has been
      focused on associations between prominent health factors and cognitive function
      in African American men, exclusively. The objective was to examine relationships
      between cardiovascular and pulmonary health, and cognitive function in African
      American men. METHOD: Data from 257 men were pooled from two studies of African
      American aging. The mean age of participants was 58.15 and mean educational
      attainment was 11.78 years. Participants provided self-reported health and
      demographic information, completed cognitive measures, and had their blood
      pressure and peak expiratory flow assessed. RESULTS: After adjustment,
      significant relationships were found between average peak expiratory flow rate
      (APEFR) and cognitive performance measures. DISCUSSION: Results suggest that lung
      function is important to consider when examining cognitive function in African
      American men. Understanding the role of health in cognition and implications for
      quality of life in this population will be critical as life expectancies
      increase.

PMID- 25053803
TI  - On the complexity of chloroplast RNA metabolism: psaA trans-splicing can be
      bypassed in chlamydomonas.
AB  - In the chloroplast, the posttranscriptional steps of gene expression are
      remarkably complex. RNA maturation and translation rely on a large cohort of
      nucleus-encoded proteins that act specifically on a single target transcript or a
      small set of targets. For example in the chloroplast of Chlamydomonas, trans
      splicing of the two split introns of psaA requires at least 14 nucleus-encoded
      proteins. To investigate the functional significance of this complex trans
      splicing pathway, we have introduced an intron-less copy of psaA in the
      chloroplast genomes of three mutants deficient in trans-splicing and of the wild
      type. We find that the intron-less psaA gene rescues the mutant phenotypes. The
      growth of strains with the intron-less psaA is indistinguishable from the wild
      type under the set of different experimental conditions that were investigated.
      Thus, the trans-splicing factors do not appear to have any other essential
      function and trans-splicing of psaA can be bypassed. We discuss how these
      observations support the hypothesis that complex RNA metabolism in the
      chloroplast may in part be the result of a nonadaptive evolutionary ratchet.
      Genetic drift may lead to the accumulation of chloroplast mutations and the
      recruitment of compensatory nuclear suppressors from large preexisting pools of
      genes encoding RNA-binding proteins. 

PMID- 25053804
TI  - The scent of royalty: a p450 gene signals reproductive status in a social insect.
AB  - Cooperation requires communication; this applies to animals and humans alike. The
      main communication means differ between taxa and social insects (ants, termites,
      and some bees and wasps) lack the cognitive abilities of most social vertebrates.
      Central to the regulation of the reproductive harmony in insect societies is the
      production of a royalty scent which signals the fertility status of the
      reproducing queen to the nonreproducing workers. Here, we revealed a central
      genetic component underlying this hallmark of insect societies in the termite
      Cryptotermes secundus. Communication between queens and workers relied upon the
      expression of a gene, Neofem4, which belongs to the cytochrome P450 genes. We
      inhibited Neofem4 in queens by RNA interference. This resulted in the loss of the
      royalty scent in queens and the workers behaved as though the queen were absent.
      The queen's behavior was not generally affected by silencing Neofem4. This
      suggests that the lack of the royalty scent lead to workers not recognizing her
      anymore as queen. P450 genes are known to be involved in the production of
      chemical signals in cockroaches and their expression has been linked to a major
      fertility regulator, juvenile hormone. This makes P450 genes, both a suitable and
      available evolutionary substrate in the face of natural selection for production
      of a queen substance. Our data suggest that in an organism without elaborate
      cognitive abilities communication has been achieved by the exploitation of a
      central gene that links the fertility network with the chemical communication
      pathway. As termites and social Hymenoptera seem to share the same class of
      compounds in signaling fertility, this role of P450 genes might be more
      widespread across social insects. 

PMID- 25053805
TI  - DRO1 inactivation drives colorectal carcinogenesis in ApcMin/+ mice.
AB  - Colorectal cancer develops from adenomatous precursor lesions by a multistep
      process that involves several independent mutational events in oncogenes and
      tumor suppressor genes. Inactivation of the adenomatous polyposis coli (APC)
      tumor suppressor gene is an early event and a prerequisite for the development of
      human colorectal adenoma. Previous in vitro studies identified DRO1 (CCDC80) to
      be a putative tumor suppressor gene that is negatively regulated in colorectal
      cancers and downregulated upon neoplastic transformation of epithelial cells. To
      investigate the in vivo role of DRO1 in colorectal carcinogenesis, a constitutive
      DRO1 knockout mouse model was generated. Disruption of DRO1 did not result in
      spontaneous intestinal tumor formation, consistent with the notion that DRO1
      might have a role in suppressing the development of colon tumors in Apc(Min) (/+)
      mice, a widely used model for studying the role of APC in intestinal
      tumorigenesis that is hampered by the fact that mice predominantly develop
      adenomas in the small intestine and not in the colon. Here, deletion of DRO1 in
      Apc(Min) (/+) mice results in earlier death, a dramatically increased colonic
      tumor burden, and frequent development of colorectal carcinoma. Furthermore,
      enhanced phosphorylation of ERK1/2 is observed in colon epithelium and tumors
      from DRO1 knockout mice. Thus, this study reveals that inactivation of DRO1 is
      required for colorectal carcinogenesis in the Apc(Min) (/+) mouse and establishes
      a new mouse model for the study of colorectal cancer. IMPLICATIONS: This report
      characterizes a new mouse model for the study of colorectal cancer and
      establishes DRO1 (CCDC80) as a tumor suppressor via a mechanism involving ERK
      phosphorylation.

PMID- 25053806
TI  - Differential requirement for Src family tyrosine kinases in the initiation,
      progression, and metastasis of prostate cancer.
AB  - Prostate cancer (CaP) recurrence after androgen ablation therapy remains a
      significant cause of mortality in aging men. Malignant progression and metastasis
      are typically driven by genetic and epigenetic changes controlled by the androgen
      receptor (AR). However, evidence suggests that activated nonreceptor tyrosine
      kinases, including those of the Src family kinases (SFK), directly phosphorylate
      AR, thereby activating its transcriptional activity in the absence of serum
      androgen levels. To ascertain whether CaP progression and metastasis require SFK
      members, an autochthonous transgenic adenocarcinoma (AD) of the mouse prostate
      (TRAMP) model was crossed into Src-, Lyn- or Fyn-null backgrounds. Primary-site
      CaP formation was dependent on Src, to a lesser extent, Lyn, but not Fyn. Only
      Src(-) (/) (-);TRAMP prostate tumors were marked by reactive stroma. SFK
      deficiency did not affect progression to neuroendocrine (NE) disease, although
      there were fewer new cancer cases initiating after 34 weeks in the SFK(-/-);TRAMP
      mice compared with TRAMP controls. Of note, 15% to 21% of older (>33 weeks) Lyn-
      or Fyn-null TRAMP mice lacking primary-site tumors suffered from aggressive
      metastatic AD growths, compared with 3% of TRAMP mice. Taken with the data that
      TRAMP mice lacking Src or Lyn exhibited fewer macroscopic metastases compared
      with Fyn(-) (/) (-);TRAMP and TRAMP controls, this suggests that SFK can either
      promote or suppress specific parameters of metastatic growth, possibly depending
      on cross-talk with primary tumors. These data identify critical, yet potentially
      opposing roles played by various SFKs in the initiation and metastatic potential
      of CaP using the TRAMP model. IMPLICATIONS: Genetically defined mouse models
      indicate a critical role for Src tyrosine kinase in CaP initiation and metastatic
      progression.

PMID- 25053807
TI  - RABbing cancer the wrong way.

PMID- 25053808
TI  - Stationary nanoliter droplet array with a substrate of choice for single
      adherent/nonadherent cell incubation and analysis.
AB  - Microfluidic water-in-oil droplets that serve as separate, chemically isolated
      compartments can be applied for single-cell analysis; however, to investigate
      encapsulated cells effectively over prolonged time periods, an array of droplets
      must remain stationary on a versatile substrate for optimal cell compatibility.
      We present here a platform of unique geometry and substrate versatility that
      generates a stationary nanodroplet array by using wells branching off a main
      microfluidic channel. These droplets are confined by multiple sides of a nanowell
      and are in direct contact with a biocompatible substrate of choice. The device is
      operated by a unique and reversed loading procedure that eliminates the need for
      fine pressure control or external tubing. Fluorocarbon oil isolates the droplets
      and provides soluble oxygen for the cells. By using this approach, the metabolic
      activity of single adherent cells was monitored continuously over time, and the
      concentration of viable pathogens in blood-derived samples was determined
      directly by measuring the number of colony-formed droplets. The method is simple
      to operate, requires a few microliters of reagent volume, is portable, is
      reusable, and allows for cell retrieval. This technology may be particularly
      useful for multiplexed assays for which prolonged and simultaneous visual
      inspection of many isolated single adherent or nonadherent cells is required. 

PMID- 25053809
TI  - Vapor-deposited glasses provide clearer view of two-level systems.

PMID- 25053810
TI  - Helical motion of the cell body enhances Caulobacter crescentus motility.
AB  - We resolve the 3D trajectory and the orientation of individual cells for extended
      times, using a digital tracking technique combined with 3D reconstructions. We
      have used this technique to study the motility of the uniflagellated bacterium
      Caulobacter crescentus and have found that each cell displays two distinct modes
      of motility, depending on the sense of rotation of the flagellar motor. In the
      forward mode, when the flagellum pushes the cell, the cell body is tilted with
      respect to the direction of motion, and it precesses, tracing out a helical
      trajectory. In the reverse mode, when the flagellum pulls the cell, the
      precession is smaller and the cell has a lower translation distance per rotation
      period and thus a lower motility. Using resistive force theory, we show how the
      helical motion of the cell body generates thrust and can explain the direction
      dependent changes in swimming motility. The source of the cell body precession is
      believed to be associated with the flexibility of the hook that connects the
      flagellum to the cell body. 

PMID- 25053811
TI  - Adaptor protein DOK3 promotes plasma cell differentiation by regulating the
      expression of programmed cell death 1 ligands.
AB  - The adaptor Downstream-of-Kinase (DOK) 3 functions as a negative regulator and
      attenuates B-cell receptor-mediated calcium signaling. Although DOK3 is
      dispensable for early B-cell development, its role in plasma cell (PC)
      differentiation is unknown. Here, we show that Dok3(-/-) mice have increased
      populations of T follicular-helper (Tfh) and germinal center (GC) B cells upon
      immunization with a T-cell-dependent antigen. However, interestingly, they
      generate significantly fewer PCs. Bone marrow reconstitution experiments show
      that the PC defect is B-cell intrinsic and due to the inability of Dok3(-/-) B
      cells to sustain programmed cell death 1 (PD-1) ligand 1 (PDL1) and up-regulate
      PD-1 ligand 2 (PDL2) expressions that are critical for PC differentiation.
      Overexpression of PDL2 rectifies the PC differentiation defect in Dok3(-/-) B
      cells. We further demonstrate that calcium signaling suppresses the transcription
      of PD-1 ligands. Abrogation of calcium signaling in B cells by deleting BTK or
      PLCgamma2 or inhibiting calcineurin with cyclosporine A leads to increased
      expression of PD-1 ligands. Thus, our study reveals DOK3 as a nonredundant
      regulator of PC differentiation by up-regulating PD-1 ligand expression through
      the attenuation of calcium signaling. 

PMID- 25053812
TI  - The Golgi localized bifunctional UDP-rhamnose/UDP-galactose transporter family of
      Arabidopsis.
AB  - Plant cells are surrounded by a cell wall that plays a key role in plant growth,
      structural integrity, and defense. The cell wall is a complex and diverse
      structure that is mainly composed of polysaccharides. The majority of
      noncellulosic cell wall polysaccharides are produced in the Golgi apparatus from
      nucleotide sugars that are predominantly synthesized in the cytosol. The
      transport of these nucleotide sugars from the cytosol into the Golgi lumen is a
      critical process for cell wall biosynthesis and is mediated by a family of
      nucleotide sugar transporters (NSTs). Numerous studies have sought to
      characterize substrate-specific transport by NSTs; however, the availability of
      certain substrates and a lack of robust methods have proven problematic.
      Consequently, we have developed a novel approach that combines reconstitution of
      NSTs into liposomes and the subsequent assessment of nucleotide sugar uptake by
      mass spectrometry. To address the limitation of substrate availability, we also
      developed a two-step reaction for the enzymatic synthesis of UDP-l-rhamnose (Rha)
      by expressing the two active domains of the Arabidopsis UDP-l-Rha synthase. The
      liposome approach and the newly synthesized substrates were used to analyze a
      clade of Arabidopsis NSTs, resulting in the identification and characterization
      of six bifunctional UDP-l-Rha/UDP-d-galactose (Gal) transporters (URGTs). Further
      analysis of loss-of-function and overexpression plants for two of these URGTs
      supported their roles in the transport of UDP-l-Rha and UDP-d-Gal for matrix
      polysaccharide biosynthesis. 

PMID- 25053813
TI  - Toll-like receptor 9 signaling acts on multiple elements of the germinal center
      to enhance antibody responses.
AB  - Recent studies have demonstrated important roles of nucleic acid-sensing Toll
      like receptors (TLRs) in promoting protective antibody responses against several
      viruses. To dissect how recognition of nucleic acids by TLRs enhances germinal
      center (GC) responses, mice selectively deleted for myeloid differentiation
      primary-response protein 88 (MyD88) in B cells or dendritic cells (DCs) were
      immunized with a haptenated protein antigen bound to a TLR9 ligand. TLR9
      signaling in DCs led to greater numbers of follicular helper T (TFH) cells and GC
      B cells, and accelerated production of broad-affinity antihapten IgG. In addition
      to modulating GC selection by increasing inducible costimulator (ICOS) expression
      on TFH cells and reducing the number of follicular regulatory T cells, MyD88
      dependent signaling in B cells enhanced GC output by augmenting a class switch to
      IgG2a, affinity maturation, and the memory antibody response. Thus, attachment of
      a TLR9 ligand to an oligovalent antigen acted on DCs and B cells to coordinate
      changes in the T-cell compartment and also promoted B cell-intrinsic effects that
      ultimately programmed a more potent GC response. 

PMID- 25053815
TI  - Intravital imaging of cardiac function at the single-cell level.
AB  - Knowledge of cardiomyocyte biology is limited by the lack of methods to
      interrogate single-cell physiology in vivo. Here we show that contracting
      myocytes can indeed be imaged with optical microscopy at high temporal and
      spatial resolution in the beating murine heart, allowing visualization of
      individual sarcomeres and measurement of the single cardiomyocyte contractile
      cycle. Collectively, this has been enabled by efficient tissue stabilization, a
      prospective real-time cardiac gating approach, an image processing algorithm for
      motion-artifact-free imaging throughout the cardiac cycle, and a fluorescent
      membrane staining protocol. Quantification of cardiomyocyte contractile function
      in vivo opens many possibilities for investigating myocardial disease and
      therapeutic intervention at the cellular level. 

PMID- 25053814
TI  - Genomics and host specialization of honey bee and bumble bee gut symbionts.
AB  - Gilliamella apicola and Snodgrassella alvi are dominant members of the honey bee
      (Apis spp.) and bumble bee (Bombus spp.) gut microbiota. We generated complete
      genomes of the type strains G. apicola wkB1(T) and S. alvi wkB2(T) (isolated from
      Apis), as well as draft genomes for four other strains from Bombus. G. apicola
      and S. alvi were found to occupy very different metabolic niches: The former is a
      saccharolytic fermenter, whereas the latter is an oxidizer of carboxylic acids.
      Together, they may form a syntrophic network for partitioning of metabolic
      resources. Both species possessed numerous genes [type 6 secretion systems,
      repeats in toxin (RTX) toxins, RHS proteins, adhesins, and type IV pili] that
      likely mediate cell-cell interactions and gut colonization. Variation in these
      genes could account for the host fidelity of strains observed in previous
      phylogenetic studies. Here, we also show the first experimental evidence, to our
      knowledge, for this specificity in vivo: Strains of S. alvi were able to colonize
      their native bee host but not bees of another genus. Consistent with specific,
      long-term host association, comparative genomic analysis revealed a deep
      divergence and little or no gene flow between Apis and Bombus gut symbionts.
      However, within a host type (Apis or Bombus), we detected signs of horizontal
      gene transfer between G. apicola and S. alvi, demonstrating the importance of the
      broader gut community in shaping the evolution of any one member. Our results
      show that host specificity is likely driven by multiple factors, including direct
      host-microbe interactions, microbe-microbe interactions, and social transmission.

PMID- 25053817
TI  - Cutaneous leishmaniasis in a returning UK traveller.

PMID- 25053816
TI  - Metaproteomics reveals differential modes of metabolic coupling among ubiquitous
      oxygen minimum zone microbes.
AB  - Marine oxygen minimum zones (OMZs) are intrinsic water column features arising
      from respiratory oxygen demand during organic matter degradation in stratified
      waters. Currently OMZs are expanding due to global climate change with resulting
      feedback on marine ecosystem function. Here we use metaproteomics to chart
      spatial and temporal patterns of gene expression along defined redox gradients in
      a seasonally stratified fjord to better understand microbial community responses
      to OMZ expansion. The expression of metabolic pathway components for
      nitrification, anaerobic ammonium oxidation (anammox), denitrification, and
      inorganic carbon fixation were differentially expressed across the redoxcline and
      covaried with distribution patterns of ubiquitous OMZ microbes including
      Thaumarchaeota, Nitrospina, Nitrospira, Planctomycetes, and SUP05/ARCTIC96BD-19
      Gammaproteobacteria. Nitrification and inorganic carbon fixation pathways
      affiliated with Thaumarchaeota dominated dysoxic waters, and denitrification,
      sulfur oxidation, and inorganic carbon fixation pathways affiliated with the
      SUP05 group of nitrate-reducing sulfur oxidizers dominated suboxic and anoxic
      waters. Nitrifier nitrite oxidation and anammox pathways affiliated with
      Nirospina, Nitrospira, and Planctomycetes, respectively, also exhibited redox
      partitioning between dysoxic and suboxic waters. The numerical abundance of SUP05
      proteins mediating inorganic carbon fixation under anoxic conditions suggests
      that SUP05 will become increasingly important in global ocean carbon and nutrient
      cycling as OMZs expand. 

PMID- 25053818
TI  - Identification of aggregation inhibitors of the human antibody light chain
      repertoire by phage display.
AB  - Protein aggregation hinders the development of biologics and underpins the
      molecular basis of many human diseases. Considerable variation of aggregation
      propensity exists not only between different proteins, but also within a single
      homologous family, which complicates analyses. A classic example is observed
      among human antibody light chains, which aggregate in a clonally specific manner,
      driven by sequence diversity within their variable domains. Here, we utilise a
      library versus library strategy, based on phage display and a chemical library of
      FDA approved drugs, to overcome this limitation. Our approach allowed the
      identification of small molecule drugs that inhibit the aggregation of the human
      light chain repertoire. It also provides a general template for the small
      molecule targeting of diverse protein families. 

PMID- 25053819
TI  - Redirected T-cell killing of solid cancers targeted with an anti-CD3/Trop-2
      bispecific antibody is enhanced in combination with interferon-alpha.
AB  - Trop-2 has limited presence on normal tissues but is highly expressed in diverse
      epithelial cancers. (E1)-3s is a T-cell-redirecting trivalent bispecific antibody
      (bsAb), comprising an anti-CD3 scFv covalently linked to a stabilized dimer of a
      Trop-2-targeting Fab using Dock-and-Lock. We show for the first time that bsAb
      mediated bidirectional trogocytosis occurs between target and T cells and
      involves immunologic synapses. We studied the effects of interferon-alpha
      (INFalpha) on (E1)-3s-mediated T-cell killing of human gastric and pancreatic
      cancer cell lines. T-cell activation, cytokine induction, and cytotoxicity were
      evaluated ex vivo using peripheral blood mononuclear cells (PBMC) or T cells with
      NCI-N87 gastric cancer as target cells. In vivo activity was assayed with NCI-N87
      and Capan-1 (pancreatic) xenografts. In the presence of target cells and PBMCs,
      (E1)-3s did not cause excess cytokine production. When combined with (E1)-3s,
      peginterferonalfa-2a--which alone did not increase T-cell activation or raise
      cytokine levels over baseline--increased CD69 expression but did not
      significantly increase cytokine induction. (E1) 3s mediated a highly potent T
      cell lysis of NCI-N87 target cells in vitro. Inclusion of peginterferonalfa-2a or
      a more potent form of INFalpha, 20*-2b, significantly potentiated the activity of
      (E1)-3s by more than 2.5- or 7-fold, respectively. In vivo, combining
      peginterferonalfa-2a with (E1)-3s delayed Capan-1 growth longer than each single
      agent. Similarly, combination therapy delayed tumor proliferation of NCI-N87
      compared with (E1)-3s or peginterferonalfa-2a single-treatment groups. (E1)-3s
      effectively induced T-cell-mediated killing of Trop-2-expressing pancreatic and
      gastric cancers, which was enhanced with INFalpha.

PMID- 25053820
TI  - Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
AB  - miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to
      regulate cell-cycle progression and apoptosis. With apparent roles in metastasis
      and cancer stem cell development, miR34a provides an interesting opportunity for
      therapeutic development. A mimic of miR34a was complexed with an amphoteric
      liposomal formulation and tested in two different orthotopic models of liver
      cancer. Systemic dosing of the formulated miR34a mimic increased the levels of
      miR34a in tumors by approximately 1,000-fold and caused statistically significant
      decreases in the mRNA levels of several miR34a targets. The administration of the
      formulated miR34a mimic caused significant tumor growth inhibition in both models
      of liver cancer, and tumor regression was observed in more than one third of the
      animals. The antitumor activity was observed in the absence of any
      immunostimulatory effects or dose-limiting toxicities. Accumulation of the
      formulated miR34a mimic was also noted in the spleen, lung, and kidney,
      suggesting the potential for therapeutic use in other cancers.

PMID- 25053821
TI  - Activation of Nrf2 pathways correlates with resistance of NSCLC cell lines to
      CBP501 in vitro.
AB  - CBP501 is an anticancer drug candidate that was investigated in two randomized
      phase II clinical trials for patients with nonsquamous non-small cell lung cancer
      (NSCLC) and malignant pleural mesothelioma (MPM). CBP501 has been shown to have
      two mechanisms of action, namely calmodulin modulation and G2 checkpoint
      abrogation. Here, we searched for a biomarker to predict sensitivity to CBP501.
      Twenty-eight NSCLC cell lines were classified into two subgroups, CBP501
      sensitive and -insensitive, by quantitatively analyzing the cis-diamminedichloro
      platinum (II) (CDDP)-enhancing activity of CBP501 through treatments with short
      term (1 hour) coexposure to CDDP and CBP501 or to either alone. Microarray
      analysis was performed on these cell lines to identify gene expression patterns
      that correlated with CBP501 sensitivity. We found that multiple nuclear factor
      erythroid-2-related factor 2 (Nrf2) target genes showed high expression in CBP501
      insensitive cell lines. Western blot and immunocytochemical analysis for Nrf2 in
      NSCLC cell lines also indicated higher protein level in CBP501-insensitive cell
      lines. Moreover, CBP501 sensitivity is modulated by silencing or sulforaphane
      induced overexpression of Nrf2. These results indicate that Nrf2 transcription
      factor is a potential candidate as a biomarker for resistance to CBP501. This
      study might help to identify those subpopulations of patients who would respond
      well to the CBP501 and CDDP combination treatment of NSCLC.

PMID- 25053822
TI  - An in vivo antilymphatic screen in zebrafish identifies novel inhibitors of
      mammalian lymphangiogenesis and lymphatic-mediated metastasis.
AB  - The growth of new lymphatic vessels (lymphangiogenesis) in tumors is an integral
      step in the metastatic spread of tumor cells, first to the sentinel lymph nodes
      that surround the tumor and then elsewhere in the body. Currently, no selective
      agents designed to prevent lymphatic vessel growth have been approved for
      clinical use, and there is an important potential clinical niche for
      antilymphangiogenic agents. Using a zebrafish phenotype-based chemical screen, we
      have identified drug compounds, previously approved for human use, that have
      antilymphatic activity. These include kaempferol, a natural product found in
      plants; leflunomide, an inhibitor of pyrimidine biosynthesis; and cinnarizine and
      flunarizine, members of the type IV class of calcium channel antagonists.
      Antilymphatic activity was confirmed in a murine in vivo lymphangiogenesis
      Matrigel plug assay, in which kaempferol, leflunomide, and flunarizine prevented
      lymphatic growth. We show that kaempferol is a novel inhibitor of VEGFR2/3 kinase
      activity and is able to reduce the density of tumor-associated lymphatic vessels
      as well as the incidence of lymph node metastases in a metastatic breast cancer
      xenograft model. However, in this model, kaempferol administration was also
      associated with tumor deposits in the pancreas and diaphragm, and flunarizine was
      found to be tumorigenic. Although this screen revealed that zebrafish is a viable
      platform for the identification and development of mammalian antilymphatic
      compounds, it also highlights the need for focused secondary screens to ensure
      appropriate efficacy of hits in a tumor context.

PMID- 25053823
TI  - Selective release of a cyclopamine glucuronide prodrug toward stem-like cancer
      cell inhibition in glioblastoma.
AB  - Recent data suggest that inhibition of the Hedgehog pathway could be a
      therapeutic target for glioblastoma. Alkaloid cyclopamine inhibits Hedgehog
      signaling, depleting stem-like cancer cells derived from glioblastoma. However,
      this compound is toxic for somatic stem cells, preventing its use for clinical
      applications. In this study, we tested a derivatization product of cyclopamine in
      the form of cyclopamine glucuronide prodrug (CGP-2). This compound was used in
      vitro and in vivo toward glioblastoma-initiating cells (GIC). Results obtained in
      vitro indicate that CGP-2 is active only in the presence of beta-glucuronidase,
      an enzyme detected in high levels in necrotic areas of glioblastomas. CGP-2
      decreased proliferation and inhibited the self-renewal of all GIC lines tested.
      Hedgehog pathway blockade by 10 MUmol/L of CGP-2 induced a 99% inhibition of
      clonogenicity on GICs, similar to cyclopamine treatment. Combination of CGP-2
      with radiation decreased clonogenic survival in all GIC lines compared with CGP-2
      alone. In a subcutaneous glioblastoma xenograft model, a two-week CGP-2 treatment
      prevented tumor growth with 75% inhibition at 8 weeks, and this inhibition was
      still significant after 14 weeks. Unlike cyclopamine, CGP-2 had no detectable
      toxic effects in intestinal crypts. Our study suggests that inhibition of the
      Hedgehog pathway with CGP-2 is more effective than conventional temozolomide
      adjuvant, with much lower concentrations, and seems to be an effective
      therapeutic strategy for targeting GICs.

PMID- 25053824
TI  - Temozolomide induces the production of epidermal growth factor to regulate MDR1
      expression in glioblastoma cells.
AB  - Glioblastoma multiforme (GBM) commonly resists the frontline chemotherapy
      treatment temozolomide. The multidrug resistance gene (MDR1) and its protein, P
      glycoprotein (P-gp), are associated with chemoresistance. This study investigated
      the mechanisms underlying MDR1-mediated resistance by GBM to temozolomide. P-gp
      trafficking was studied by flow cytometry and Western blot analysis. MDR1
      expression was analyzed by real-time PCR and reporter gene assays. AP-1
      interaction with MDR1 was studied by chromatin immunoprecipitation assay. EGF
      production was analyzed by ELISA, EGFR signaling was determined by Western blot
      analysis, and in vivo response to erlotinib and/or temozolomide was studied in
      nude mice. During the early phase of temozolomide treatment, intracellular P-gp
      was trafficked to the cell membrane, followed by conformational change into
      active P-gp. At the later phase, gene transcription of MDR1 was induced by
      temozolomide-mediated production of EGF. EGF activated ERK1/2-JNK-AP-1 cofactors
      (c-jun and c-fos). An inhibitor of EGFR kinase (erlotinib) given to nude mice
      with GBM prevented temozolomide-induced resistance. The results identified an
      essential role for activated EGFR in the resistance of GBM to temozolomide.
      Temozolomide resistance occurred through a biphasic response; first, by a
      conformational change in P-gp into the active form and, second, by releasing EGF,
      which caused autocrine stimulation of GBM cells to induce MDR1. Pharmacologic
      inhibition of EGFR kinase blunted the ability of GBM cells to resist
      temozolomide. These findings may explain reports on the common occurrence of
      mutant EGFR (EGFRvIII) and EGFR expansion in the resistance of GBM cells.

PMID- 25053826
TI  - BRCA2 and RAD51 promote double-strand break formation and cell death in response
      to gemcitabine.
AB  - Replication inhibitors cause replication fork stalling and double-strand breaks
      (DSB) that result from processing of stalled forks. During recovery from
      replication blocks, the homologous recombination (HR) factor RAD51 mediates fork
      restart and DSB repair. HR defects therefore sensitize cells to replication
      inhibitors, with clear implications for cancer therapy. Gemcitabine is a potent
      replication inhibitor used to treat cancers with mutations in HR genes such as
      BRCA2. Here, we investigate why, paradoxically, mutations in HR genes protect
      cells from killing by gemcitabine. Using DNA replication and DNA damage assays in
      mammalian cells, we show that even short gemcitabine treatments cause persistent
      replication inhibition. BRCA2 and RAD51 are recruited to chromatin early after
      removal of the drug, actively inhibit replication fork progression, and promote
      the formation of MUS81- and XPF-dependent DSBs that remain unrepaired. Our data
      suggest that HR intermediates formed at gemcitabine-stalled forks are converted
      into DSBs and thus contribute to gemcitabine-induced cell death, which could have
      implications for the treatment response of HR-deficient tumors.

PMID- 25053827
TI  - A combined teamwork training and work standardisation intervention in operating
      theatres: controlled interrupted time series study.
AB  - BACKGROUND: Teamwork training and system standardisation have both been proposed
      to reduce error and harm in surgery. Since the approaches differ markedly, there
      is potential for synergy between them. METHODS:  DESIGN: Controlled interrupted
      time series with a 3 month intervention and observation phases before and after.
      SETTING: Operating theatres conducting elective orthopaedic surgery in a single
      hospital system (UK Hospital Trust). INTERVENTION: Teamwork training based on
      crew resource management plus training and follow-up support in developing
      standardised operating procedures. Focus of subsequent standardisation efforts
      decided by theatre staff. MEASURES: Paired observers watched whole procedures
      together. We assessed non-technical skills using NOTECHS II, technical
      performance using glitch rate and compliance with WHO checklist using a simple
      quality tool. We measured complication and readmission rates and hospital stay
      using hospital administrative records. Before/after change was compared in the
      active and control groups using two-way ANOVA and regression models. RESULTS:
      1121 patients were operated on before and 1100 after intervention. 44 operations
      were observed before and 50 afterwards. Non-technical skills (p=0.002) and WHO
      compliance (p<0.001) improved significantly after the intervention in the active
      versus the control group. Glitch count improved in both groups and there was no
      significant effect on clinical outcomes. DISCUSSION: Combined training in
      teamwork and system improvement causes marked improvements in team behaviour and
      WHO performance, but not technical performance or outcome. These findings are
      consistent with the synergistic hypothesis, but larger controlled studies with a
      strong implementation strategy are required to test potential outcome effects.

PMID- 25053825
TI  - BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase
      inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT
      ITD.
AB  - Recently, treatment with bromodomain and extraterminal protein antagonist (BA)
      such as JQ1 has been shown to inhibit growth and induce apoptosis of human acute
      myelogenous leukemia (AML) cells, including those expressing FLT3-ITD. Here, we
      demonstrate that cotreatment with JQ1 and the FLT3 tyrosine kinase inhibitor
      (TKI) ponatinib or AC220 synergistically induce apoptosis of cultured and primary
      CD34(+) human AML blast progenitor cells (BPC) expressing FLT3-ITD.
      Concomitantly, as compared with each agent alone, cotreatment with JQ1 and the
      FLT3-TKI caused greater attenuation of c-MYC, BCL2, and CDK4/6. Simultaneously,
      cotreatment with JQ1 and the FLT3-TKI increased the levels of p21, BIM, and
      cleaved PARP, as well as mediated marked attenuation of p-STAT5, p-AKT, and p
      ERK1/2 levels in AML BPCs. Conversely, cotreatment with JQ1 and FLT3-TKI was
      significantly less active against CD34(+) normal bone marrow progenitor cells.
      Knockdown of BRD4 by short hairpin RNA also sensitized AML cells to FLT3-TKI. JQ1
      treatment induced apoptosis of mouse Ba/F3 cells ectopically expressing FLT3-ITD
      with or without FLT3-TKI-resistant mutations F691L and D835V. Compared with the
      parental human AML FLT3-ITD-expressing MOLM13, MOLM13-TKIR cells resistant to
      AC220 were markedly more sensitive to JQ1-induced apoptosis. Furthermore,
      cotreatment with JQ1 and the pan-histone deacetylase inhibitor (HDI) panobinostat
      synergistically induced apoptosis of FLT3-TKI-resistant MOLM13-TKIR and MV4-11
      TKIR cells. Collectively, these findings support the rationale for determining
      the in vivo activity of combined therapy with BA and FLT3-TKI against human AML
      cells expressing FLT3-ITD or with BA and HDI against AML cells resistant to FLT3
      TKI.

PMID- 25053828
TI  - Respiratory failure secondary to relapsing polychondritis.

PMID- 25053829
TI  - Unilateral hyperlucent lung associated with bronchial atresia mimicking Swyer
      James syndrome.

PMID- 25053830
TI  - Filamin A mutation may be associated with diffuse lung disease mimicking
      bronchopulmonary dysplasia in premature newborns.
AB  - Bronchopulmonary dysplasia (BPD) is a common long-term complication in premature
      newborns requiring ventilatory support and is the most common cause of chronic
      diffuse lung disease in this population. We present the clinical course of a
      premature newborn with a complicated neonatal respiratory course that was
      initially thought to be related to BPD, but it did not respond to the typical
      therapies for this condition. Due to the findings of periventricular nodular
      heterotopia, the diagnosis of a filamin A gene mutation was eventually made,
      which explained the respiratory pathology of this patient. When time of onset and
      clinical course do not correlate with typical BPD, one should consider
      alternative diagnoses in premature infants, including neonatal diffuse lung
      disease. 

PMID- 25053831
TI  - Spillover of cytokines and reactive oxygen species in ventilator-induced lung
      injury associated with inflammation and apoptosis in distal organs.
AB  - BACKGROUND: The mechanism between ventilator-induced lung injury (VILI) and
      multiple organ injury is unclear. The aim of our study was to investigate the
      mechanisms of VILI-induced distal organ injury. METHODS: VILI was induced in rat
      lungs with high tidal volume (V(T)) ventilation of 40 mL/kg for 6 h. Rats with
      low V(T) ventilation of 6 mL/kg served as controls. Inflammatory and apoptotic
      indices in lung and distal organs were assessed. RESULTS: VILI increased lung
      weight, airway pressure, inflammation, and apoptotic pathologic changes without
      hemodynamic changes. The white blood cell count and the levels of H2O2,
      interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and macrophage
      inflammatory protein-2 in bronchoalveolar lavage fluid were higher in the VILI
      group compared with the control group. H2O2, IL-1beta, and tumor necrosis factor
      alpha in blood from the left ventricle were up-regulated. H2O2, IL-1beta, tumor
      necrosis factor alpha, macrophage inflammatory protein-2, c-Jun N-terminal
      kinase, p38, nuclear factor kappa B, and caspase-3 in lung, heart, liver, and
      kidney tissues in the VILI group were up-regulated. Furthermore, the apoptotic
      score for the kidneys was higher than those for other distal organs in the VILI
      group. CONCLUSIONS: High V(T) ventilation induces VILI and is associated with
      inflammation and apoptosis in distal organs. Up-regulation of reactive oxygen
      species and cytokines in VILI is associated with systemic inflammatory responses.
      Kidney tissue appears to be more vulnerable than heart and liver tissues
      following VILI.

PMID- 25053832
TI  - CD147 up-regulates calcium-induced chemotaxis, adhesion ability and invasiveness
      of human neutrophils via a TRPM-7-mediated mechanism.
AB  - OBJECTIVES: We aimed to investigate whether CD147 can up-regulate the
      chemotactic, adhesive and invasive properties of human neutrophils and to
      determine the mechanism underlying this process. METHODS: Human promyelocytic
      leukaemia cells (HL-60) cells and peripheral blood or synovial fluid neutrophils
      were isolated from RA patients. Under cyclophilin A (CypA) stimulation,
      chemotaxis, adhesion potential and invasion ability were assessed using
      chemotaxis, adhesion and invasiveness assays. Lipid raft isolation and western
      blot were used to determine the mechanism underlying the effects of CypA
      stimulation. RESULTS: CD147 up-regulates the calcium-induced chemotaxis, adhesion
      ability and invasiveness of human neutrophils in RA patients. Transient receptor
      potential melastatin 7 may be responsible for this phenomenon. CONCLUSION: These
      findings suggest that in RA patients, abundant CypA up-regulates the calcium
      induced chemotactic, adhesive and invasive properties of neutrophils via direct
      binding to CD147. Cyclophilin-CD147 interactions might contribute to the
      destruction of cartilage and bone in RA.

PMID- 25053833
TI  - Repression of cell proliferation by miR319-regulated TCP4.
AB  - Leaf development has been extensively studied on a genetic level. However, little
      is known about the interplay between the developmental regulators and the cell
      cycle machinery--a link that ultimately affects leaf form and size. miR319 is a
      conserved microRNA that regulates TCP transcription factors involved in multiple
      developmental pathways, including leaf development and senescence, organ
      curvature, and hormone biosynthesis and signaling. Here, we analyze the
      participation of TCP4 in the control of cell proliferation. A small increase in
      TCP4 activity has an immediate impact on leaf cell number, by significantly
      reducing cell proliferation. Plants with high TCP4 levels have a strong reduction
      in the expression of genes known to be active in G2-M phase of the cell cycle.
      Part of these effects is mediated by induction of miR396, which represses Growth
      Regulating Factor (GRF) transcription factors. Detailed analysis revealed TCP4 to
      be a direct regulator of MIR396b. However, we found that TCP4 can control cell
      proliferation through additional pathways, and we identified a direct connection
      between TCP4 and ICK1/KRP1, a gene involved in the progression of the cell cycle.
      Our results show that TCP4 can activate different pathways that repress cell
      proliferation.

PMID- 25053834
TI  - Quantitation of enantiomers of r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10
      tetrahydrobenzo[a]-pyrene in human urine: evidence supporting metabolic
      activation of benzo[a]pyrene via the bay region diol epoxide.
AB  - Benzo[a]pyrene (BaP), a potent polycyclic aromatic hydrocarbon carcinogen, is
      widely distributed in the human environment. All humans are exposed to BaP
      through the diet and contact with the general environment; cigarette smokers have
      higher exposure. An important pathway of BaP metabolism proceeds through
      formation of diol epoxides including the 'bay region diol epoxide' 7R,8S
      dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [BaP-(7R,8S)-diol
      (9S,10R)-epoxide] and the 'reverse diol epoxide' 9S,10R-dihydroxy-7R,8S-epoxy
      7,8,9,10-tetrahydrobenzo [a]pyrene [BaP-(9S,10R)-diol-(7R,8S)-epoxide]. The bay
      region diol epoxide is considered a major ultimate carcinogen of BaP based on
      studies in cell culture and laboratory animals, but the available data in humans
      are less convincing. The bay region diol epoxide and the reverse diol epoxide
      react with H2O to produce enantiomeric BaP-tetraols that are excreted in the
      urine. We used chiral stationary-phase high-performance liquid chromatography and
      gas chromatography-negative ion chemical ionisation-tandem mass spectrometry to
      quantify these enantiomeric BaP-tetraols in the urine of 25 smokers and 25 non
      smokers. The results demonstrated that the BaP-tetraol enantiomer representing
      the carcinogenic bay region diol epoxide pathway accounted for 68+/-6% (range 56
      81%) of total BaP-tetraol in smokers and 64+/-6% (range 46-78%) in non-smokers.
      Levels of the major BaP-tetraol enantiomer decreased by 75% in smokers who quit
      smoking. These data provide convincing evidence in support of the bay region diol
      epoxide mechanism of BaP carcinogenesis in humans. 

PMID- 25053835
TI  - Comparative evaluation of genotoxicity by micronucleus assay in the buccal mucosa
      over comet assay in peripheral blood in oral precancer and cancer patients.
AB  - Early detection and quantification of DNA damage in oral premalignancy or
      malignancy may help in management of the disease and improve survival rates. The
      comet assay has been successfully utilised to detect DNA damage in oral
      premalignant or malignancy. However, due to the invasive nature of collecting
      blood, it may be painful for many unwilling patients. This study compares the
      micronucleus (MN) assay in oral buccal mucosa cells with the comet assay in
      peripheral blood cells in a subset of oral habit-induced precancer and cancer
      patients. For this, MN assay of exfoliated epithelial cells was compared with
      comet assay of peripheral blood leucocytes among 260 participants, including
      those with oral lichen planus (OLP; n = 52), leukoplakia (LPK; n = 51), oral
      submucous fibrosis (OSF; n = 51), oral squamous cell carcinoma (OSCC; n = 54) and
      normal volunteers (n = 52). Among the precancer groups, LPK patients showed
      significantly higher levels of DNA damage as reflected by both comet tail length
      (P < 0.0001) and micronuclei (MNi) frequency (P = 0.0009). The DNA damage pattern
      in precancer and cancer patients was OLP < OSF < LPK < OSCC, and with respective
      oral habits, it was multiple habits > cigarette + khaini > cigarette smokers >
      areca + khaini > areca. There was no significant difference in the comet length
      and MNi frequency between males and females who had oral chewing habits. An
      overall significant correlation was observed between MNi frequency and comet tail
      length with r = 0.844 and P < 0.0001. Thus, the extent of DNA damage evaluation
      by the comet assay in peripheral blood cells is perfectly reflected by the MN
      assay on oral exfoliated epithelial cells, and MNi frequency can be used with the
      same effectiveness and greater efficiency in early detection of oral premalignant
      conditions. 

PMID- 25053836
TI  - Crystal structure of DnaT84-153-dT10 ssDNA complex reveals a novel single
      stranded DNA binding mode.
AB  - DnaT is a primosomal protein that is required for the stalled replication fork
      restart in Escherichia coli. As an adapter, DnaT mediates the PriA-PriB-ssDNA
      ternary complex and the DnaB/C complex. However, the fundamental function of DnaT
      during PriA-dependent primosome assembly is still a black box. Here, we report
      the 2.83 A DnaT(84-153)-dT10 ssDNA complex structure, which reveals a novel three
      helix bundle single-stranded DNA binding mode. Based on binding assays and
      negative-staining electron microscopy results, we found that DnaT can bind to
      phiX 174 ssDNA to form nucleoprotein filaments for the first time, which
      indicates that DnaT might function as a scaffold protein during the PriA
      dependent primosome assembly. In combination with biochemical analysis, we
      propose a cooperative mechanism for the binding of DnaT to ssDNA and a possible
      model for the assembly of PriA-PriB-ssDNA-DnaT complex that sheds light on the
      function of DnaT during the primosome assembly and stalled replication fork
      restart. This report presents the first structure of the DnaT C-terminal complex
      with ssDNA and a novel model that explains the interactions between the three
      helix bundle and ssDNA. 

PMID- 25053837
TI  - Single-cell RNA-seq: advances and future challenges.
AB  - Phenotypically identical cells can dramatically vary with respect to behavior
      during their lifespan and this variation is reflected in their molecular
      composition such as the transcriptomic landscape. Single-cell transcriptomics
      using next-generation transcript sequencing (RNA-seq) is now emerging as a
      powerful tool to profile cell-to-cell variability on a genomic scale. Its
      application has already greatly impacted our conceptual understanding of diverse
      biological processes with broad implications for both basic and clinical
      research. Different single-cell RNA-seq protocols have been introduced and are
      reviewed here-each one with its own strengths and current limitations. We further
      provide an overview of the biological questions single-cell RNA-seq has been used
      to address, the major findings obtained from such studies, and current challenges
      and expected future developments in this booming field. 

PMID- 25053839
TI  - A novel phosphorylation-independent interaction between SMG6 and UPF1 is
      essential for human NMD.
AB  - Eukaryotic mRNAs with premature translation-termination codons (PTCs) are
      recognized and eliminated by nonsense-mediated mRNA decay (NMD). NMD substrates
      can be degraded by different routes that all require phosphorylated UPF1 (P-UPF1)
      as a starting point. The endonuclease SMG6, which cleaves mRNA near the PTC, is
      one of the three known NMD factors thought to be recruited to nonsense mRNAs via
      an interaction with P-UPF1, leading to eventual mRNA degradation. By artificial
      tethering of SMG6 and mutants thereof to a reporter mRNA combined with knockdowns
      of various NMD factors, we demonstrate that besides its endonucleolytic activity,
      SMG6 also requires UPF1 and SMG1 to reduce reporter mRNA levels. Using in vivo
      and in vitro approaches, we further document that SMG6 and the unique stalk
      region of the UPF1 helicase domain, along with a contribution from the SQ domain,
      form a novel interaction and we also show that this region of the UPF1 helicase
      domain is critical for SMG6 function and NMD. Our results show that this
      interaction is required for NMD and for the capability of tethered SMG6 to
      degrade its bound RNA, suggesting that it contributes to the intricate regulation
      of UPF1 and SMG6 enzymatic activities. 

PMID- 25053838
TI  - The effect of Pot1 binding on the repair of thymine analogs in a telomeric DNA
      sequence.
AB  - Telomeric DNA can form duplex regions or single-stranded loops that bind multiple
      proteins, preventing it from being processed as a DNA repair intermediate. The
      bases within these regions are susceptible to damage; however, mechanisms for the
      repair of telomere damage are as yet poorly understood. We have examined the
      effect of three thymine (T) analogs including uracil (U), 5-fluorouracil (5FU)
      and 5-hydroxymethyluracil (5hmU) on DNA-protein interactions and DNA repair
      within the GGTTAC telomeric sequence. The replacement of T with U or 5FU
      interferes with Pot1 (Pot1pN protein of Schizosaccharomyces pombe) binding.
      Surprisingly, 5hmU substitution only modestly diminishes Pot1 binding suggesting
      that hydrophobicity of the T-methyl group likely plays a minor role in protein
      binding. In the GGTTAC sequence, all three analogs can be cleaved by DNA
      glycosylases; however, glycosylase activity is blocked if Pot1 binds. An abasic
      site at the G or T positions is cleaved by the endonuclease APE1 when in a duplex
      but not when single-stranded. Abasic site formation thermally destabilizes the
      duplex that could push a damaged DNA segment into a single-stranded loop. The
      inability to enzymatically cleave abasic sites in single-stranded telomere
      regions would block completion of the base excision repair cycle potentially
      causing telomere attrition. 

PMID- 25053840
TI  - Major capsid reinforcement by a minor protein in herpesviruses and phage.
AB  - Herpes simplex type 1 virus (HSV-1) and bacteriophage lambda capsids undergo
      considerable structural changes during self-assembly and DNA packaging. The
      initial steps of viral capsid self-assembly require weak, non-covalent
      interactions between the capsid subunits to ensure free energy minimization and
      error-free assembly. In the final stages of DNA packaging, however, the internal
      genome pressure dramatically increases, requiring significant capsid strength to
      withstand high internal genome pressures of tens of atmospheres. Our data reveal
      that the loosely formed capsid structure is reinforced post-assembly by the minor
      capsid protein UL25 in HSV-1 and gpD in bacteriophage lambda. Using atomic force
      microscopy nano-indentation analysis, we show that the capsid becomes stiffer
      upon binding of UL25 and gpD due to increased structural stability. At the same
      time the force required to break the capsid increases by ~70% for both herpes and
      phage. This demonstrates a universal and evolutionarily conserved function of the
      minor capsid protein: facilitating the retention of the pressurized viral genome
      in the capsid. Since all eight human herpesviruses have UL25 orthologs, this
      discovery offers new opportunities to interfere with herpes replication by
      disrupting the precise force balance between the encapsidated DNA and the capsid
      proteins crucial for viral replication. 

PMID- 25053841
TI  - Induction and suppression of tick cell antiviral RNAi responses by tick-borne
      flaviviruses.
AB  - Arboviruses are transmitted by distantly related arthropod vectors such as
      mosquitoes (class Insecta) and ticks (class Arachnida). RNA interference (RNAi)
      is the major antiviral mechanism in arthropods against arboviruses. Unlike in
      mosquitoes, tick antiviral RNAi is not understood, although this information is
      important to compare arbovirus/host interactions in different classes of
      arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute
      proteins involved in RNAi and the response against tick-borne Langat virus
      (Flaviviridae) replication were identified and phylogenetic relationships
      characterized. Analysis of small RNAs in infected cells showed the production of
      virus-derived small interfering RNAs (viRNAs), which are key molecules of the
      antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than
      those from other arbovirus vectors and mapped at highest frequency to the termini
      of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick
      borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick
      RNAi. Our results characterize the antiviral RNAi response in tick cells
      including phylogenetic analysis of genes encoding antiviral proteins, and viral
      interference with this pathway. This shows important differences in antiviral
      RNAi between the two major classes of arbovirus vectors, and our data broadens
      our understanding of arthropod antiviral RNAi. 

PMID- 25053842
TI  - miRdentify: high stringency miRNA predictor identifies several novel animal
      miRNAs.
AB  - During recent years, miRNAs have been shown to play important roles in the
      regulation of gene expression. Accordingly, much effort has been put into the
      discovery of novel uncharacterized miRNAs in various organisms. miRNAs are
      structurally defined by a hairpin-loop structure recognized by the two-step
      processing apparatus, Drosha and Dicer, necessary for the production of mature ~
      22-nucleotide miRNA guide strands. With the emergence of high-throughput
      sequencing applications, tools have been developed to identify miRNAs and profile
      their expression based on sequencing reads. However, as the read depth increases,
      false-positive predictions increase using established algorithms, underscoring
      the need for more stringent approaches. Here we describe a transparent pipeline
      for confident miRNA identification in animals, termed miRdentify. We show that
      miRdentify confidently discloses more than 400 novel miRNAs in humans, including
      the first male-specific miRNA, which we successfully validate. Moreover, novel
      miRNAs are predicted in the mouse, the fruit fly and nematodes, suggesting that
      the pipeline applies to all animals. The entire software package is available at
      www.ncrnalab.dk/mirdentify.

PMID- 25053843
TI  - dREAM co-operates with insulator-binding proteins and regulates expression at
      divergently paired genes.
AB  - dREAM complexes represent the predominant form of E2F/RBF repressor complexes in
      Drosophila. dREAM associates with thousands of sites in the fly genome but its
      mechanism of action is unknown. To understand the genomic context in which dREAM
      acts we examined the distribution and localization of Drosophila E2F and dREAM
      proteins. Here we report a striking and unexpected overlap between dE2F2/dREAM
      sites and binding sites for the insulator-binding proteins CP190 and Beaf-32.
      Genetic assays show that these components functionally co-operate and chromatin
      immunoprecipitation experiments on mutant animals demonstrate that dE2F2 is
      important for association of CP190 with chromatin. dE2F2/dREAM binding sites are
      enriched at divergently transcribed genes, and the majority of genes upregulated
      by dE2F2 depletion represent the repressed half of a differentially expressed,
      divergently transcribed pair of genes. Analysis of mutant animals confirms that
      dREAM and CP190 are similarly required for transcriptional integrity at these
      gene pairs and suggest that dREAM functions in concert with CP190 to establish
      boundaries between repressed/activated genes. Consistent with the idea that dREAM
      co-operates with insulator-binding proteins, genomic regions bound by dREAM
      possess enhancer-blocking activity that depends on multiple dREAM components.
      These findings suggest that dREAM functions in the organization of
      transcriptional domains. 

PMID- 25053844
TI  - Activity-associated miRNA are packaged in Map1b-enriched exosomes released from
      depolarized neurons.
AB  - Rapid input-restricted change in gene expression is an important aspect of
      synaptic plasticity requiring complex mechanisms of post-transcriptional mRNA
      trafficking and regulation. Small non-coding miRNA are uniquely poised to support
      these functions by providing a nucleic-acid-based specificity component for
      universal-sequence-dependent RNA binding complexes. We investigated the
      subcellular distribution of these molecules in resting and potassium chloride
      depolarized human neuroblasts, and found both selective enrichment and depletion
      in neurites. Depolarization was associated with a neurite-restricted decrease in
      miRNA expression; a subset of these molecules was recovered from the
      depolarization medium in nuclease resistant extracellular exosomes. These
      vesicles were enriched with primate specific miRNA and the synaptic-plasticity
      associated protein MAP1b. These findings further support a role for miRNA as
      neural plasticity regulators, as they are compartmentalized in neurons and
      undergo activity-associated redistribution or release into the extracellular
      matrix. 

PMID- 25053845
TI  - Is an observed non-co-linear RNA product spliced in trans, in cis or just in
      vitro?
AB  - Global transcriptome investigations often result in the detection of an enormous
      number of transcripts composed of non-co-linear sequence fragments. Such
      'aberrant' transcript products may arise from post-transcriptional events or
      genetic rearrangements, or may otherwise be false positives (sequencing/alignment
      errors or in vitro artifacts). Moreover, post-transcriptionally non-co-linear
      ('PtNcl') transcripts can arise from trans-splicing or back-splicing in cis (to
      generate so-called 'circular RNA'). Here, we collected previously-predicted human
      non-co-linear RNA candidates, and designed a validation procedure integrating in
      silico filters with multiple experimental validation steps to examine their
      authenticity. We showed that >50% of the tested candidates were in vitro
      artifacts, even though some had been previously validated by RT-PCR. After
      excluding the possibility of genetic rearrangements, we distinguished between
      trans-spliced and circular RNAs, and confirmed that these two splicing forms can
      share the same non-co-linear junction. Importantly, the experimentally-confirmed
      PtNcl RNA events and their corresponding PtNcl splicing types (i.e. trans
      splicing, circular RNA, or both sharing the same junction) were all expressed in
      rhesus macaque, and some were even expressed in mouse. Our study thus describes
      an essential procedure for confirming PtNcl transcripts, and provides further
      insight into the evolutionary role of PtNcl RNA events, opening up this
      important, but understudied, class of post-transcriptional events for
      comprehensive characterization. 

PMID- 25053846
TI  - G-quadruplexes are specifically recognized and distinguished by selected designed
      ankyrin repeat proteins.
AB  - We introduce designed ankyrin repeat binding proteins (DARPins) as a novel class
      of highly specific and structure-selective DNA-binding proteins, which can be
      functionally expressed within all cells. Human telomere quadruplex was used as
      target to select specific binders with ribosome display. The selected DARPins
      discriminate the human telomere quadruplex against the telomeric duplex and other
      quadruplexes. Affinities of the selected binders range from 3 to 100 nM. CD
      studies confirm that the quadruplex fold is maintained upon binding. The DARPins
      show different specificity profiles: some discriminate human telomere
      quadruplexes from other quadruplex-forming sequences like ILPR, c-MYC and c-KIT,
      while others recognize two of the sequences tested or even all quadruplexes. None
      of them recognizes dsDNA. Quadruplex-binding DARPins constitute valuable tools
      for specific detection at very small scales and for the in vivo investigation of
      quadruplex DNA. 

PMID- 25053847
TI  - Inhibition of RNA binding to hepatitis C virus RNA-dependent RNA polymerase: a
      new mechanism for antiviral intervention.
AB  - The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) is a key target
      for antiviral intervention. The goal of this study was to identify the binding
      site and unravel the molecular mechanism by which natural flavonoids efficiently
      inhibit HCV RdRp. Screening identified the flavonol quercetagetin as the most
      potent inhibitor of HCV RdRp activity. Quercetagetin was found to inhibit RdRp
      through inhibition of RNA binding to the viral polymerase, a yet unknown
      antiviral mechanism. X-ray crystallographic structure analysis of the RdRp
      quercetagetin complex identified quercetagetin's binding site at the entrance of
      the RNA template tunnel, confirming its original mode of action. This antiviral
      mechanism was associated with a high barrier to resistance in both site-directed
      mutagenesis and long-term selection experiments. In conclusion, we identified a
      new mechanism for non-nucleoside inhibition of HCV RdRp through inhibition of RNA
      binding to the enzyme, a mechanism associated with broad genotypic activity and a
      high barrier to resistance. Our results open the way to new antiviral approaches
      for HCV and other viruses that use an RdRp based on RNA binding inhibition, that
      could prove to be useful in human, animal or plant viral infections. 

PMID- 25053848
TI  - The dialysis scenario in patients with systemic lupus erythematosus.
AB  - Although prognosis of lupus nephritis has improved over time, a substantial
      amount of lupus patients still reach end-stage renal disease and require
      dialysis. Treatment of these patients can be challenging, since the disease poses
      a number of problems that can portend a poor prognosis, such as infections, lupus
      reactivations, vascular access thrombosis and cardiovascular complications.
      Consensus is lacking among investigators about the real incidence of these
      complications and related diagnosis and treatment. Moreover, the choice of the
      type of dialysis treatment and the overall prognosis are still a matter of
      debate. In this paper, we have reviewed the currently available literature in an
      attempt to answer the most controversial issues about the topic. 

PMID- 25053852
TI  - Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on
      survival in patients with non-small cell lung cancer treated with radiotherapy
      for brain metastases.
AB  - BACKGROUND: We determined the impact of genetic alterations in EGFR, ALK, or KRAS
      on survival after radiotherapy for brain metastases in non-small cell lung cancer
      (NSCLC). METHODS: Of 172 genotyped NSCLC patients treated with radiotherapy for
      brain metastases in 2005-2012, 54 had cancers with EGFR mutations, 12 had ALK
      rearrangements, 38 had KRAS mutations, and 68 were wild-type (WT). Overall
      survival (OS) was determined. RESULTS: Median follow-up was 8.6 months. Median OS
      was 13.6 months for patients with EGFR mutations and 26.3 months for patients
      with ALK rearrangements, in contrast to 5.7 months for KRAS-mutant patients and
      5.5 months for WT patients (P = .001). On multivariate analysis, adjusting for
      receipt of targeted therapy after cranial radiotherapy, ALK rearrangements were
      associated with improved OS (HR, 0.31; 95% CI, 0.13-0.74; P = .008). EGFR
      mutations were not significantly associated with improved OS on multivariate
      analysis (HR, 0.71; 95% CI, 0.37-1.38; P = .3). KRAS mutations were also not
      associated with improved OS (HR, 0.93; 95% CI, 0.59-1.47; P = .8). Receipt of
      targeted therapy after cranial radiotherapy was independently associated with
      improved OS (HR, 0.30; 95% CI, 0.17-0.54; P < .001). Receipt of chemotherapy
      after cranial radiotherapy, number of brain metastases, extracranial metastases,
      age, and performance status were also associated with OS. CONCLUSIONS: NSCLC
      patients with genetic alterations in ALK have improved survival outcomes after
      radiotherapy for brain metastases compared with EGFR, KRAS, or WT. Subsequent
      receipt of targeted therapy was associated with additional improvement in OS.

PMID- 25053854
TI  - Is deferred use of bevacizumab for glioblastoma associated with prolonged
      survival?

PMID- 25053853
TI  - Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma.
AB  - BACKGROUND: 3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of
      cancer-cell specific aerobic glycolysis. Their application in glioma is limited
      by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting
      toxicity. The safety and efficacy of intracranial delivery of these compounds
      were assessed. METHODS: Cytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L,
      and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable
      pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats.
      Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a
      rodent allograft model of high-grade glioma, both as a monotherapy and in
      combination with temozolomide (TMZ) and radiation therapy (XRT). RESULTS: 3-BrPA
      and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5%
      3-BrPA wafer-treated animals had significantly increased survival compared with
      controls (P = .0027). The median survival of rats with the 50% DCA wafer
      increased significantly compared with both the oral DCA group (P = .050) and the
      controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination
      with TMZ had significantly increased survival over either therapy alone. No
      statistical difference in survival was noted when the wafers were added to the
      combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in
      combination with TMZ and XRT resulted in long-term survivorship of 30%.
      CONCLUSION: Intracranial delivery of 3-BrPA and DCA polymer was safe and
      significantly increased survival in an animal model of glioma, a potential novel
      therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a
      synergistic effect.

PMID- 25053859
TI  - Aspects of Experimental Errors and Data Reduction Schemes From Spherical
      Indentation of Isotropic Materials.
AB  - Sensitivity to experimental errors determines the reliability and usefulness of
      any experimental investigation. Thus, it is important to understand how various
      test techniques are affected by expected experimental errors. Here, a semi
      analytical method based on the concept of condition number is explored for
      systematic investigation of the sensitivity of spherical indentation to
      experimental errors. The method is employed to investigate the reliability of
      various possible spherical indentation protocols, providing a ranking of the
      selected data reduction protocols from least to most sensitive to experimental
      errors. Explicit Monte Carlo sensitivity analysis is employed to provide further
      insight of selected protocol, supporting the ranking. The results suggest that
      the proposed method for estimating the sensitivity to experimental errors is a
      useful tool. Moreover, in the case of spherical indentation, the experimental
      errors must be very small to give reliable material properties.

PMID- 25053860
TI  - Analytical Investigation of Elastic Thin-Walled Cylinder and Truncated Cone Shell
      Intersection Under Internal Pressure.
AB  - An elastic solution of cylinder-truncated cone shell intersection under internal
      pressure is presented. The edge solution theory that has been used in this study
      takes bending moments and shearing forces into account in the thin-walled shell
      of revolution element. The general solution of the cone equations is based on
      power series method. The effect of cone apex angle on the stress distribution in
      conical and cylindrical parts of structure is investigated. In addition, the
      effect of the intersection and boundary locations on the circumferential and
      longitudinal stresses is evaluated and it is shown that how quantitatively they
      are essential.

PMID- 25053855
TI  - Efficacy and Tolerability of Nilvadipine in Combination with an Angiotensin II
      Receptor Antagonist in Patients with Essential Hypertension: A Multicenter, Open
      Label, Uncontrolled Study.
AB  - BACKGROUND: Combination therapy with different classes of antihypertensive drugs
      often is needed to achieve controlled blood pressure (BP). The combination of an
      angiotensin II receptor antagonist (AIIA) and a calcium antagonist is a preferred
      option for reducing uncontrolled BP. OBJECTIVE: The aim of this study was to
      assess the clinical efficacy and tolerability of nilvadipine, a dihydropyridine
      calcium antagonist, in combination with an AIIA. METHODS: Patients with essential
      hypertension whose BP was not controlled by an AIIA alone were eligible for this
      multicenter, open-label, uncontrolled study. One of 3 AIIAs (candesartan
      cilexetil, losartan potassium, or valsartan) was given for at least 10 weeks
      before the addition of nilvadipine (daily dose, 4 or 8 mg orally). This
      combination therapy was given for 8 weeks. BP and heart rate were measured
      between 2 and 4 weeks before and 0, 4, and 8 weeks after the start of combination
      therapy. Adverse events were monitored at each visit. RESULTS: Thirty-one
      patients (18 women [58.1%], 13 men [41.9%]; mean [SD] age, 58.5 [10.5] years)
      were enrolled. At weeks 4 and 8 of combination therapy, mean systolic BP (SBP)
      and diastolic BP (DBP) were significantly decreased (P<0.01) (at week 8, by 22.0
      mm Hg and 12.5 mm Hg, respectively). The mean BP-lowering effect did not differ
      significantly between the 3 AIIAs tested. Pulse pressure also decreased
      significantly at week 8, by 9.6 mm Hg (P<0.01). The responder rate (ie, the
      percentage of patients with DBP <90 mm Hg or a decrease in DBP >=10 mm Hg) was
      72.0% at week 8. Three patients experienced a total of 4 adverse events: mild or
      severe flushing, mild headache, and mild palpitation. All of these symptoms
      resolved after nilvadipine treatment was discontinued. CONCLUSIONS: Nilvadipine
      in combination with an AIIA showed good antihypertensive efficacy and was well
      tolerated in the hypertensive patients in this study. This combination also
      significantly decreased pulse pressure, suggesting that this combination therapy
      also may have a beneficial effect in elderly patients with isolated systolic
      hypertension.

PMID- 25053861
TI  - Study of the Reynolds Number Effect on the Process of Instability Transition Into
      the Turbulent Stage.
AB  - The results of the experimental study of the Reynolds number effect on the
      process of the Rayleigh-Taylor (R-T) instability transition into the turbulent
      stage are presented. The experimental liquid layer was accelerated by compressed
      gas. Solid particles were scattered on the layer free surface to specify the
      initial perturbations in some experiments. The process was recorded with the use
      of a high-speed motion picture camera. The following results were obtained in
      experiments: (1) Long-wave perturbation is developed at the interface at the
      Reynolds numbers Re < 104. If such perturbation growth is limited by a hard wall,
      the jet directed in gas is developed. If there is no such limitation, this
      perturbation is resolved into the short-wave ones with time, and their growth
      results in gas-liquid mixing. (2) Short-wave perturbations specified at the
      interface significantly reduce the Reynolds number Re for instability to pass
      into the turbulent mixing stage.

PMID- 25053862
TI  - The state of irreversible electroporation in interventional oncology.
AB  - A new ablation modality, irreversible electroporation (IRE), has been of
      increasing interest in interventional radiology. Its nonthermal mechanism of
      action of killing tumor cells allows physicians the ability to ablate tumors in
      areas previously contraindicated for thermal ablation. This article reviews the
      current published clinical outcomes, imaging follow-up, and the current knowledge
      gaps in the procedure for patients treated with IRE. 

PMID- 25053863
TI  - Thermal ablation of stage I non-small cell lung carcinoma.
AB  - Ablation options for the treatment of localized non-small cell lung carcinoma
      (NSCLC) include radiofrequency ablation, microwave ablation, and cryotherapy.
      Irreversible electroporation is a novel ablation method with the potential of
      application to lung tumors in risky locations. This review article describes the
      established and novel ablation techniques used in the treatment of localized
      NSCLC, including mechanism of action, indications, potential complications,
      clinical outcomes, postablation surveillance, and use in combination with other
      therapies. 

PMID- 25053864
TI  - Laparoscopic-assisted ablation of hepatic tumors: a review.
AB  - Thermal ablation of hepatic tumors has been an evolving field over the last two
      decades. It is used in the treatment of both primary and metastatic neoplasms,
      and with evolutions in the technology, there has been an increasing interest in
      treating lesions where hepatic resection is not an option. Laparoscopic or
      minimally invasive surgical procedures have also advanced during this same time
      period, and the interface of these tools has been associated with the genesis of
      a new approach for treating hepatic lesions which are located in difficult to
      reach locations or found immediately adjacent to other intra-abdominal organs.
      This review summarizes the published literature focusing on the treatment of
      primary and metastatic neoplasms located in the liver, including a review of
      outcomes. 

PMID- 25053865
TI  - Bone and soft tissue ablation.
AB  - Bone and soft tissue tumor ablation has reached widespread acceptance in the
      locoregional treatment of various benign and malignant musculoskeletal (MSK)
      lesions. Many principles of ablation learned elsewhere in the body are easily
      adapted to the MSK system, particularly the various technical aspects of
      probe/antenna design, tumoricidal effects, selection of image guidance, and
      methods to reduce complications. Despite the common use of thermal and chemical
      ablation procedures in bone and soft tissues, there are few large clinical series
      that show longitudinal benefit and cost-effectiveness compared with conventional
      methods, namely, surgery, external beam radiation, and chemotherapy. Percutaneous
      radiofrequency ablation of osteoid osteomas has been evaluated the most and is
      considered a first-line treatment choice for many lesions. Palliation of painful
      metastatic bone disease with thermal ablation is considered safe and has been
      shown to reduce pain and analgesic use while improving quality of life for cancer
      patients. Procedure-related complications are rare and are typically easily
      managed. Similar to all interventional procedures, bone and soft tissue lesions
      require an integrated approach to disease management to determine the optimum
      type of and timing for ablation techniques within the context of the patient care
      plan. 

PMID- 25053866
TI  - Technical and practical considerations for device selection in locoregional
      ablative therapy.
AB  - Percutaneous ablation therapy is an essential component of contemporary
      interventional oncologic therapy of primary and secondary malignancies. The
      growing armamentarium of available ablation technologies calls for thorough
      understanding of the different ablation modalities to optimize device selection
      in individual clinical settings. The goal of the current article is to provide
      direction on ablative device selection by reviewing device mechanisms of action,
      advantages and disadvantages, and practical considerations in real-life case
      scenarios. 

PMID- 25053867
TI  - The Biomimetic Shark Skin Optimization Design Method for Improving Lubrication
      Effect of Engineering Surface.
AB  - Nature has long been an important source of inspiration for mankind to develop
      artificial ways to mimic the remarkable properties of biological systems. In this
      work, a new method was explored to fabricate a biomimetic engineering surface
      comprising both the shark-skin, the shark body denticle, and rib morphology. It
      can help reduce water resistance and the friction contact area as well as
      accommodate lubricant. The lubrication theory model was established to predict
      the effect of geometric parameters of a biomimetic surface on tribological
      performance. The model has been proved to be feasible to predict tribological
      performance by the experimental results. The model was then used to investigate
      the effect of the grid textured surface on frictional performance of different
      geometries. The investigation was aimed at providing a rule for deriving the
      design parameters of a biomimetic surface with good lubrication characteristics.
      Results suggest that: (i) the increase in depression width ratio [Formula: see
      text] decreases its corresponding coefficient of friction, and (ii) the small
      coefficient of friction is achievable when [Formula: see text] is beyond 0.45.
      Superposition of depth ratio Gamma and angle's couple under the condition of
      [Formula: see text] < 0.45 affects the value of friction coefficient. It shows
      the decrease in angle decreases with the increase in dimension depth [Formula:
      see text].

PMID- 25053868
TI  - The Effect of Wear on the Performance of a Rotary Lip Seal.
AB  - Theoretical analysis, combined with experimental verification, is used to study
      the effect of wear on the performance of a rotary lip seal as characterized by
      the pumping rate and friction torque. The performance of a rotary lip seal is
      determined by the sealing lip surface microscopic characteristics and contact
      characteristics at the sealing zone. The variation of the contact characteristics
      with wear has been established based on the variation of the sealing lip profiles
      measured by using a trilinear coordinate measuring instrument. The impression
      method is used to copy the lip surface microtopography at different wear times
      and then an optical interferometer is used to measure the impression surface
      microtopography to obtain the variation of roughness with wear. The variations of
      the roughness, contact characteristics, and approximate contact temperature with
      wear are inserted into a mixed lubrication model to obtain the variations of the
      pumping rate and friction torque. A comparison of the simulated results with
      those from experimental measurement verifies the validity of the theoretical
      analysis.

PMID- 25053870
TI  - Application of Time-Delay Absorber to Suppress Vibration of a Dynamical System to
      Tuned Excitation.
AB  - In this work, we present a comprehensive investigation of the time delay absorber
      effects on the control of a dynamical system represented by a cantilever beam
      subjected to tuned excitation forces. Cantilever beam is one of the most widely
      used system in too many engineering applications, such as mechanical and civil
      engineering. The main aim of this work is to control the vibration of the beam at
      simultaneous internal and combined resonance condition, as it is the worst
      resonance case. Control is conducted via time delay absorber to suppress chaotic
      vibrations. Time delays often appear in many control systems in the state, in the
      control input, or in the measurements. Time delay commonly exists in various
      engineering, biological, and economical systems because of the finite speed of
      the information processing. It is a source of performance degradation and
      instability. Multiple time scale perturbation method is applied to obtain a first
      order approximation for the nonlinear differential equations describing the
      system behavior. The different resonance cases are reported and studied
      numerically. The stability of the steady-state solution at the selected worst
      resonance case is investigated applying Runge-Kutta fourth order method and
      frequency response equations via Matlab 7.0 and Maple11. Time delay absorber is
      effective, but within a specified range of time delay. It is the critical factor
      in selecting such absorber. Time delay absorber is better than the ordinary one
      as from the effectiveness point of view. The effects of the different absorber
      parameters on the system behavior and stability are studied numerically. A
      comparison with the available published work showed a close agreement with some
      previously published work.

PMID- 25053869
TI  - Enhanced apoptosis of monocytes from complication-free juvenile-onset diabetes
      mellitus type 1 may be ameliorated by TNF-alpha inhibitors.
AB  - Diabetes mellitus type 1 is associated with an enhanced apoptosis of different
      cells and tissues, accelerating occurrence of diabetic microvascular
      complications. The aim of our study was to determine spontaneous apoptotic
      potential of the monocyte subsets in juvenile-onset complication-free diabetes
      mellitus type 1 and to compare them with the corresponding values of the healthy.
      Moreover, we wanted to assess effects of TNF-R1 blocking agents and those of
      general TNF-alpha blocker (Infliximab) on spontaneous apoptosis of monocytes.
      Sixty randomly selected DM1 patients (14.5 +/- 3.2 years) and 30 healthy (13.5 +/
      2.8 years) volunteers were enrolled in the study. Our results indicate that
      three monocyte subsets are distinguishable in the groups of young diabetic
      patients and the healthy, similarly to in the blood of adults. DM1 patients were
      characterized by higher values of apoptotic monocytes than the healthy. The
      manipulation with drugs inhibiting TNF-R1 expression diminished the pool of
      CD16(+) apoptotic monocytes. Infliximab reduced the apoptotic CD16(-) cells. In
      conclusion, diabetes mellitus type 1 is associated with greater apoptosis of
      three monocyte subsets which may contribute to the development of microvascular
      complications. TNF-alpha modifiers appear to ameliorate monocyte apoptosis. They
      may be useful for controlling excessive monocyte apoptosis in diabetic patients. 

PMID- 25053871
TI  - Kinetic Shapes: Analysis, Verification, and Applications.
AB  - A circular shape placed on an incline will roll; similarly, an irregularly shaped
      object, such as the Archimedean spiral, will roll on a flat surface when a force
      is applied to its axle. This rolling is dependent on the specific shape and the
      applied force (magnitude and location). In this paper, we derive formulas that
      define the behavior of irregular 2D and 3D shapes on a flat plane when a weight
      is applied to the shape's axle. These kinetic shape (KS) formulas also define and
      predict shapes that exert given ground reaction forces when a known weight is
      applied at the axle rotation point. Three 2D KS design examples are physically
      verified statically with good correlation to predicted values. Motion simulations
      of unrestrained 2D KS yielded expected results in shape dynamics and self
      stabilization. We also put forth practical application ideas and research for 2D
      and 3D KS such as in robotics and gait rehabilitation.

PMID- 25053872
TI  - Mutation survey of candidate genes in 40 Chinese patients with congenital ectopia
      lentis.
AB  - PURPOSE: To identify the spectrum and frequency of five candidate genes in
      Chinese patients with congenital ectopia lentis (EL). METHODS: Forty consecutive
      and unrelated congenital probands with EL were collected and underwent ocular,
      skeletal, and cardiovascular examinations. Sanger sequencing was used to analyze
      all of the coding and adjacent regions of five candidate genes: FBN1, ADAMTS10,
      ADAMTSL4, TGFBR2, and CBS. Mutation analysis was performed to evaluate the
      pathogenic variants and to identify the cause of congenital EL. RESULTS: The FBN1
      gene screen revealed 25 pathogenic variants in 34 of the 40 families with
      congenital EL, including three novel (c.1955G>T, c.2222delA, and c.4381T>C) and
      22 known mutations. The ADAMTSL10 gene screen revealed a compound heterozygous
      variant (c.1586G>A and c.2485T>A) in a family with Weill-Marchesani syndrome
      (WMS). In the remaining five probands, no pathogenic variant was detected in any
      of the five screened genes. CONCLUSIONS: In this study, we identified three novel
      and 22 known mutations in FBN1 in 34 of 40 EL families. The results expand the
      mutation spectrum of the FBN1 gene and suggest that FBN1 mutations may be the
      major cause of congenital EL in Chinese patients.

PMID- 25053873
TI  - An updated meta-analysis: apolipoprotein E genotypes and risk of primary open
      angle glaucoma.
AB  - PURPOSE: To study the association of apolipoprotein E (APOE) polymorphisms and
      primary open-angle glaucoma (POAG). METHODS: After a systematic literature
      search, all relevant studies evaluating the association between APOE
      polymorphisms and POAG were included. All statistical tests were calculated with
      Stata 11.0. RESULTS: Twelve independent studies on the APOE gene (1,971 cases,
      1,756 controls) and POAG were included. A significant association between the
      APOE gene and POAG was found in the genetic model of epsilon4/epsilon4 versus
      epsilon3/epsilon3 (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.12
      3.88, p = 0.02). However, no association was detected in the models of
      epsilon2/epsilon2 versus epsilon3/epsilon3, epsilon2/epsilon3 versus
      epsilon3/epsilon3, epsilon2/epsilon4 versus epsilon3/epsilon3, epsilon3/epsilon4
      versus epsilon3/epsilon3, allele epsilon2 versus allele epsilon3, and allele
      epsilon4 versus allele epsilon3. Subgroup analyses showed that a statistically
      significant association between the APOE gene and the risk of POAG existed in the
      genetic model of epsilon4/epsilon4 versus epsilon3/epsilon3 in Asians (OR = 3.55,
      95% CI = 1.06-11.87, p = 0.04). No association was identified between the APOE
      gene and the risk of POAG in Caucasians. CONCLUSIONS: The present meta-analysis
      indicated that the epsilon4/epsilon4 genotype is associated with increased risk
      of POAG in Asians.

PMID- 25053874
TI  - Genome-wide DNA methylation profiles according to Chlamydophila psittaci
      infection and the response to doxycycline treatment in ocular adnexal lymphoma.
AB  - PURPOSE: To compare genome-wide DNA methylation profiles according to
      Chlamydophila psittaci (Cp) infection status and the response to doxycycline
      treatment in Korean patients with ocular adnexal extranodal marginal zone B-cell
      lymphoma (EMZL). METHODS: Twelve ocular adnexal EMZL cases were classified into
      two groups (six Cp-positive cases and six Cp-negative cases). Among the 12 cases,
      eight were treated with doxycycline as first-line therapy, and they were divided
      into two groups according to their response to the treatment (four doxy
      responders and four doxy-nonresponders). The differences in the DNA methylation
      states of 27,578 methylation sites in 14,000 genes were evaluated using Illumina
      bead assay technology. We also validated the top-ranking differentially
      methylated genes (DMGs) with bisulfite direct sequencing or pyrosequencing.
      RESULTS: The Infinium methylation chip assay revealed 180 DMGs in the Cp-positive
      group (74 hypermethylated genes and 106 hypomethylated genes) compared to the Cp
      negative group. Among the 180 DMGs, DUSP22, which had two significantly
      hypomethylated loci, was validated, and the correlation was significant for one
      CpG site (Spearman coefficient=0.6478, p=0.0262). Regarding the response to
      doxycycline treatment, a total of 778 DMGs were revealed (389 hypermethylated
      genes and 336 hypomethylated genes in the doxy-responder group). In a subsequent
      replication study for representative hypomethylated (IRAK1) and hypermethylated
      (CXCL6) genes, the correlation between the bead chip analysis and pyrosequencing
      was significant (Spearman coefficient=0.8961 and 0.7619, respectively, p<0.05).
      CONCLUSIONS: Ocular adnexal EMZL showed distinct methylation patterns according
      to Cp infection and the response to doxycycline treatment in this genome-wide
      methylation study. Among the candidate genes, DUSP22 has a methylation status
      that was likely attributable to Cp infection. Our data also suggest that the
      methylation statuses of IRAK1 and CXCL6 may reflect the response to doxycycline
      treatment.

PMID- 25053875
TI  - MiRNA-221 negatively regulated downstream p27Kip1 gene expression involvement in
      pterygium pathogenesis.
AB  - PURPOSE: MiRNAs are small noncoding RNAs that have been implicated in tumor
      development. They regulate target gene expression either by mRNA degradation or
      by translation repression. Activation of beta-catenin has been linked to
      pterygium progression. Here, we hypothesize that beta-catenin-associated miRNA,
      miRNA-221, and downstream p27Kip1 gene expression are correlated with the
      pathogenesis of pterygium. METHODS: We collected 120 pterygial and 120 normal
      conjunctival samples for this study. Immunohistochemistry and real-time reverse
      transcription (RT)-PCR were performed to determine beta-catenin protein
      localization, miR-221, and p27Kip1 gene expression. Pterygium cell line (PECs)
      cell models were used to confirm the effect of beta-catenin, miR-221, and p27Kip1
      gene in the proliferation of pterygium cells. RESULTS: Seventy-two (60.0%)
      pterygial specimens showed high miR-221 expression levels, which was
      significantly higher than the control groups (13 of 120, 10.8%, p<0.0001). MiR
      221 expression was significantly higher in beta-catenin-nuclear/cytoplasmic
      positive groups than in beta-catenin membrane-positive and negative groups
      (p=0.001). We also found that p27Kip1 gene expression in pterygium was negatively
      correlated with miR-221 expression (p=0.002). In the clinical association, miR
      221 expression was significantly higher in the fleshy and intermediate groups
      than in the atrophic group (p=0.007). The association of miR-221, p27Kip1 and
      proliferation of pterygium were also confirmed in the PECs model. CONCLUSIONS:
      Our study demonstrated that activation of beta-catenin in pterygium may interact
      with miR-221, resulting in p27Kip1 gene downregulation that influences pterygium
      pathogenesis.

PMID- 25053876
TI  - Stability and Transport of Graphene Oxide Nanoparticles in Groundwater and
      Surface Water.
AB  - The effects of groundwater and surface water constituents (i.e., natural organic
      matter [NOM] and the presence of a complex assortment of ions) on graphene oxide
      nanoparticles (GONPs) were investigated to provide additional insight into the
      factors contributing to fate and the mechanisms involved in their transport in
      soil, groundwater, and surface water environments. The stability and transport of
      GONPs was investigated using dynamic light scattering, electrokinetic
      characterization, and packed bed column experiments. Stability results showed
      that the hydrodynamic diameter of the GONPs at a similar ionic strength (2.1+/
      1.1 mM) was 10 times greater in groundwater environments compared with surface
      water and NaCl and MgCl2 suspensions. Transport results confirmed that in
      groundwater, GONPs are less stable and are more likely to be removed during
      transport in porous media. In surface water and MgCl2 and NaCl suspensions, the
      relative recovery was 94%+/-3% indicating that GONPs will be very mobile in
      surface waters. Additional experiments were carried out in monovalent (KCl) and
      divalent (CaCl2) salts across an environmentally relevant concentration range
      (0.1-10 mg/L) of NOM using Suwannee River humic acid. Overall, the transport and
      stability of GONPs was increased in the presence of NOM. This study confirms that
      planar "carbonaceous-oxide" materials follow traditional theory for stability and
      transport, both due to their response to ionic strength, valence, and NOM
      presence and is the first to look at GONP transport across a wide range of
      representative conditions found in surface and groundwater environments.

PMID- 25053877
TI  - Genotoxicity and Cytotoxicity of Cadmium Sulfide Nanomaterials to Mice:
      Comparison Between Nanorods and Nanodots.
AB  - Cadmium sulfide (CdS) nanomaterials (such as CdS nanodots or nanorods) are widely
      used in optical, electronic, and biological applications. Large-scale production
      and use of these materials will likely result in accidental and incidental
      releases, which raise concerns about their potential environmental and human
      health impacts. Most studies on toxicity of Cd-containing nanomaterials have
      focused on nanodots, and the relative toxicity of Cd-containing nanorods is not
      well understood. Here, we compared genotoxicity and cytotoxicity of CdS nanorods
      (30-50 nm diameter, 500-1100 nm length) and cubic CdS nanodots (3-5 nm) in mice
      by examining total cadmium accumulation in organs, acute toxicity, DNA damage,
      spermatozoon viability and abnormality, kidney and liver damage, and oxidative
      stress. Compared with (smaller) nanodots, nanorods resulted in relatively low
      bioaccumulation, acute toxicity, and damage to spermatozoa and the tested organs.
      Differences in toxicity between CdS nanodots and nanorods could not be fully
      explained by differences in their metal ion (Cd2+) release patterns, based on
      control tests with mice gavaged with dissolved CdCl2 at equivalent
      concentrations. This underscores that toxicity of metallic nanomaterials could
      not be solely predicted based either on their elemental composition or on the
      amount of ions released before receptor intake. Particle morphology (including
      size) may also need to be considered.

PMID- 25053878
TI  - Influence of Water Hardness on Silver Ion and Silver Nanoparticle Fate and
      Toxicity Toward Nitrosomonas europaea.
AB  - This study investigated the influence of water hardness (Mg2+ and Ca2+) on the
      fate and toxicity of 20 nm citrate silver nanoparticles (AgNPs) and Ag+ toward
      Nitrosomonas europaea, a model ammonia-oxidizing bacterium. Nitrification
      inhibition of N. europaea by 1 ppm AgNPs and 0.5 ppm Ag+ was reduced from 80% and
      83%, respectively, in the absence of Mg2+ to 2% and 33%, respectively, in the
      presence of 730 MUM Mg2+. Introduction of Mg2+ resulted in the rapid aggregation
      of the AgNP suspensions and reduced the 3 h Ag+ dissolution rates from 30%, in
      the absence of Mg2+, to 9%, in the presence of 730 MUM Mg2+. Reduced AgNP
      dissolution rates resulted in decreased concentrations of silver that were found
      adsorbed to N. europaea cells. Increasing AgNP concentrations in the presence of
      Mg2+ increased the observed inhibition of nitrification, but was always less than
      what was observed in the absence of Mg2+. The presence of Mg2+ also reduced the
      adsorption of Ag+ to cells, possibly due to multiple mechanisms, including a
      reduction in the negative surface charge of the N. europaea membrane and a
      competition between Mg2+ and Ag+ for membrane binding sites and transport into
      the cells. Ca2+ demonstrated similar protection mechanisms, as Ag+ toxicity was
      reduced and AgNP suspensions aggregated and decreased their dissolution rates.
      These results indicate that the toxicity of Ag+ and AgNPs to nitrifying bacteria
      in wastewater treatment would be less pronounced in systems with hard water.

PMID- 25053879
TI  - Nanostructured Graphene-Titanium Dioxide Composites Synthesized by a Single-Step
      Aerosol Process for Photoreduction of Carbon Dioxide.
AB  - Photocatalytic reduction of carbon dioxide (CO2) to hydrocarbons by using
      nanostructured materials activated by solar energy is a promising approach to
      recycling CO2 as a fuel feedstock. CO2 photoreduction, however, suffers from low
      efficiency mainly due to the inherent drawback of fast electron-hole
      recombination in photocatalysts. This work reports the synthesis of
      nanostructured composites of titania (TiO2) nanoparticles (NPs) encapsulated by
      reduced graphene oxide (rGO) nanosheets via an aerosol approach. The role of
      synthesis temperature and TiO2/GO ratio in CO2 photoreduction was investigated.
      As-prepared nanocomposites demonstrated enhanced CO2 conversion performance as
      compared with that of pristine TiO2 NPs due to the strong electron trapping
      capability of the rGO nanosheets.

PMID- 25053880
TI  - Dynamical Structure of a Traditional Amazonian Social Network.
AB  - Reciprocity is a vital feature of social networks, but relatively little is known
      about its temporal structure or the mechanisms underlying its persistence in real
      world behavior. In pursuit of these two questions, we study the stationary and
      dynamical signals of reciprocity in a network of manioc beer (Spanish: chicha;
      Tsimane': shocdye') drinking events in a Tsimane' village in lowland Bolivia. At
      the stationary level, our analysis reveals that social exchange within the
      community is heterogeneously patterned according to kinship and spatial
      proximity. A positive relationship between the frequencies at which two families
      host each other, controlling for kinship and proximity, provides evidence for
      stationary reciprocity. Our analysis of the dynamical structure of this network
      presents a novel method for the study of conditional, or non-stationary,
      reciprocity effects. We find evidence that short-timescale reciprocity (within
      three days) is present among non- and distant-kin pairs; conversely, we find that
      levels of cooperation among close kin can be accounted for on the stationary
      hypothesis alone.

PMID- 25053881
TI  - Life-threatening asthma attack during prolonged fingolimod treatment: case
      report.
AB  - BACKGROUND: Fingolimod (FTY) mediates bronchoconstriction by interacting with
      sphingosine-1-phosphate receptors. The majority of the reported adverse
      respiratory events occur during the first weeks of treatment. CASE PRESENTATION:
      A 49-year-old woman developed a life-threatening asthma attack after 6 months of
      continuous FTY treatment. The adverse event required prolonged hospitalization,
      and the patient recovered without sequelae after FTY interruption. A history of
      previous airway hyperreactivity and a concurrent viral respiratory infection
      possibly acted as predisposing factors. CONCLUSION: This first description of a
      severe, life-threatening asthma attack during prolonged FTY treatment suggests
      the need for long-term clinical surveillance, especially in patients with known
      predisposing factors.

PMID- 25053882
TI  - Biomarkers of acute myocardial infarction in the elderly: troponin and beyond.
AB  - In the broadest context, biological markers, or biomarkers, are molecules that
      characterize a biological system or process. In the setting of cardiovascular
      disease, a number of biomarkers have become an integral part of diagnostic and
      risk stratification strategies. In this review, we will discuss classic and
      emerging biomarkers of cardiovascular disease and the role of these biomarkers in
      the diagnosis and prognosis of elderly patients presenting with acute myocardial
      infarction. 

PMID- 25053883
TI  - Risk scores and geriatric profile: can they really help us in anticoagulation
      decision making among older patients suffering from atrial fibrillation?
AB  - OBJECTIVES: Anticoagulation for the prevention of cardio-embolism is most
      frequently indicated but largely underused in frail older patients with atrial
      fibrillation (AF). This study aimed at identifying characteristics associated
      with anticoagulation underuse. METHODS: A cross-sectional study of consecutive
      geriatric patients aged >=75 years, with AF and clear anticoagulation indication
      (CHADS2 [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and
      prior Stroke or transient ischemic attack] >=2) upon hospital admission. All
      patients benefited from a comprehensive geriatric assessment. Their risks of
      stroke and bleeding were predicted using CHADS2 and HEMORR2HAGES (Hepatic or
      renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet
      count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic
      factors, Excessive fall risk, and Stroke) scores, respectively. RESULTS:
      Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with
      AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%).
      No geriatric characteristic was found to be associated with anticoagulation
      underuse. Conversely, anticoagulation underuse was markedly increased in the
      patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3
      [3.8; 7.5]). Other independent predictors of anticoagulation underuse were
      ethanol abuse (OR: 4.0 [1.4; 13.3]) and age >=90 years (OR: 2.0 [1.2; 3.4]).
      Anticoagulation underuse was not inferior in patients with a lower bleeding risk
      and/or a higher stroke risk and underuse was surprisingly not inferior either in
      the AF patients who had previously had a stroke. CONCLUSION: Half of this
      geriatric population did not receive any anticoagulation despite a clear
      indication, regardless of their individual bleeding or stroke risks. Aspirin use
      is the main characteristic associated with anticoagulation underuse.

PMID- 25053884
TI  - Characterization of airway inflammation in patients with COPD using fractional
      exhaled nitric oxide levels: a pilot study.
AB  - OBJECTIVE: To characterize fractional exhaled nitric oxide (FeNO) levels that may
      be indicative of Th2-mediated airway inflammation in patients with chronic
      obstructive pulmonary disease (COPD). METHODS: This single-visit, outpatient
      study was conducted in 200 patients aged 40 years and older with COPD. All
      patients underwent spirometry and FeNO testing. COPD severity was classified
      according to the Global initiative for chronic Obstructive Lung Disease (GOLD)
      2010 guidelines. RESULTS: Patients who participated in the study had a mean age
      of 63.9 +/- 11.3 years and a mean smoking history of 46 +/- 29 pack years.
      Patients had a mean forced expiratory volume in 1 second % predicted of 53.9% +/-
      22.1%. The percentage of patients classified with COPD severity Stage I, II, III,
      and IV was 13%, 40%, 39%, and 8%, respectively. In addition, according to current
      procedural terminology codes, 32% of patients were classified as mixed
      COPD/asthma, 26% as COPD/emphysema, and 42% as all other codes. The mean FeNO
      level for all patients was 15.3 +/- 17.2 parts per billion (ppb). Overall, 89% of
      patients had a FeNO <25 ppb, 8% had a FeNO 25-50 ppb, and 3% had a FeNO >50 ppb.
      The percentages of patients with FeNO in the intermediate or high ranges of FeNO
      were greatest among patients with mixed COPD/asthma (intermediate, 11.5%; high,
      6.6%) compared with COPD/emphysema (intermediate, 8%; high, 0) and all other
      codes (intermediate, 6.3%; high, 1.3%). CONCLUSION: Increases in FeNO were
      identified in a subset of patients with COPD, particularly in those previously
      diagnosed with both COPD and asthma. Since FeNO is useful for identifying
      patients with airway inflammation who will have a beneficial response to
      treatment with an inhaled corticosteroid, these data may have important
      implications for the management of COPD patients.

PMID- 25053885
TI  - Clinical significance and association of RUNX3 hypermethylation frequency with
      colorectal cancer: a meta-analysis.
AB  - BACKGROUND: The RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a
      sequence-specific transcription factor family and is closely involved in a
      variety of cellular processes including development, differentiation,
      participation in the regulation of p53-dependent DNA damage response and/or
      tumorigenesis. Emerging evidence indicates that RUNX3 is a candidate tumor
      suppressor in several types of human tumors including colorectal cancer (CRC).
      However, the correlation of RUNX3 inactivation with CRC remains unclear. In the
      study reported here, we conducted a systematic review and meta-analysis to
      quantitatively evaluate the effects of RUNX3 hypermethylation/expression on the
      incidence of CRC. METHODS: A detailed search of the literature was made using
      Medline((r)) and Web of Science for related research publications written in
      English. The methodological quality of the studies was also evaluated. The data
      were extracted and assessed by two reviewers independently. Analyses of the
      pooled data were performed. Odds ratios (ORs) and hazard ratios were calculated
      and summarized, respectively. RESULTS: A final analysis of 1,427 CRC patients
      from eleven eligible studies was performed. We observed that RUNX3
      hypermethylation was significantly higher in CRC than in normal colorectal
      mucosa. The pooled OR from six studies comprising 289 CRC and 188 normal
      colorectal mucosa was OR =0.07 (confidence interval [CI] =0.03-0.18, P<0.00001).
      Aberrant RUNX3 hypermethylation/expression was significantly higher in advanced
      CRC than in early staged CRC (OR =0.54, CI =0.41-0.71, P<0.0001). Aberrant RUNX3
      hypermethylation/expression was also significantly higher in microsatellite
      instability (MSI)-positive CRC than in MSI-negative CRC (OR =0.44, CI =0.3-0.66,
      P<0.0001). In addition, CRC patients with RUNX3 hypermethylation or lacking RUNX3
      protein expression had a lower survival rate than those without RUNX3
      hypermethylation or those who did not express RUNX3 protein. CONCLUSION: The
      results of this meta-analysis suggest that RUNX3 hypermethylation is associated
      with an increased risk of CRC, increased risk of progression of CRC, and a poorer
      CRC survival rate. RUNX3 hypermethylation, which induces the inactivation of
      RUNX3 gene, plays an important role in colorectal carcinogenesis, high levels of
      MSI, as well as CRC progression and development.

PMID- 25053886
TI  - Salivary expression of soluble HER2 in breast cancer patients with positive and
      negative HER2 status.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      salivary concentration of the soluble fragment of the HER2 (human epidermal
      growth factor receptor) protein and its status in mammary tissues. METHODS: This
      case-control study was done in 27 breast cancer patients with no visible
      metastatic disease treated at the gynecology service, Maternity Souissi Hospital,
      Rabat, Morocco. Two groups were selected, ie, patients with positive and negative
      HER2 status in mammary tissue. The salivary HER2 protein concentration was
      assessed by enzyme-linked immunosorbent assay. The salivary HER2 concentration
      was compared between the HER2-positive and HER2-negative groups using the Mann
      Whitney U test. A P-value <0.05 was considered to be statistically significant.
      RESULTS: No statistically significant difference in salivary HER2 protein
      expression was found between the case and control groups. There was also no
      significant difference in clinical characteristics according to positive and
      negative HER2 status (P>0.05), except for the progesterone hormone receptor which
      was statistically significant in both the case and control groups (P=0.047).
      CONCLUSION: According to our data, salivary expression of the HER2 receptor may
      not be a reliable alternative to tissue assessment.

PMID- 25053887
TI  - Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid
      cancer.
AB  - Recent Phase III data presented at the American Society of Clinical Oncology
      (ASCO) 2013 annual conference by Brose et al led to the US Food and Drug
      Administration (FDA) approval of sorafenib for the treatment of well
      differentiated radioactive iodine-resistant metastatic thyroid cancer. This is
      the second drug in 40 years to be FDA approved for this indication. Recent
      reviews and a meta-analysis reveal a modest ability to induce a partial remission
      but substantial ability to halt disease progression. Given the significant
      activating mutations present in thyroid cancer, many of which are inhibited by
      sorafenib, the next logical approach may be to combine targeted rational
      therapies if permitted by collective toxicity profiles. This systematic review
      aims to summarize the recent Phase II/III data leading to the FDA approval of
      sorafenib for radioactive iodine therapy differentiated thyroid cancer and
      highlights recent novel combination therapy trials. 

PMID- 25053888
TI  - Impact of therapeutic drug monitoring of antiretroviral drugs in routine clinical
      management of patients infected with human immunodeficiency virus and related
      health care costs: a real-life study in a large cohort of patients.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced morbidity
      and mortality in patients infected with human immunodeficiency virus (HIV).
      Studies have documented high interindividual variability in the pharmacokinetics
      of antiretroviral drugs, which may impair the success of HAART if not managed
      properly. Therapeutic drug monitoring (TDM) is a useful diagnostic tool that
      helps clinicians to optimize drug doses so that drug concentrations associated
      with the highest therapeutic efficacy are obtained with a reduced risk of
      concentration-dependent adverse effects. The aim of this study was to assess
      whether use of TDM improves clinical outcomes and cost of illness. METHODS: A
      retrospective cohort study was conducted at L Sacco University Hospital in Milan,
      Italy, in HIV-infected patients aged >=18 years with at least one prescription of
      antiretroviral drugs for which TDM was applied. The inclusion period was from
      January 2010 to December 2011, with a follow-up period of up to 12 months.
      Laboratory and administrative databases were analyzed and matched with each
      other. RESULTS: The cohort consisted of 5,347 patients (3,861 males and 1,486
      females) of mean age 43.9+/-12.5 years. We found that TDM had been used in 143 of
      these patients, among whom adherence with therapy was significantly higher than
      among those in whom TDM had not been used (94% versus 78%). In TDM-controlled
      patients, the mean length of HIV-related hospitalization stay and mean cost of
      hospitalization were significantly reduced with respect to those observed in the
      group in which TDM had not been used (7.21 days versus 29.47 days and ?293 versus
      ?688, respectively). CONCLUSION: Inclusion of TDM as part of routine clinical
      optimization of drug dosing in HIV-infected patients is associated with higher
      adherence to therapy, reduced length of hospitalization stay, and reduced cost of
      illness.

PMID- 25053889
TI  - Endoscopic removal of foreign bodies from the upper gastrointestinal tract: 5
      year experience.
AB  - BACKGROUND: Foreign bodies (FBs) in the upper gastrointestinal tract are produced
      chiefly by accidental swallowing but rarely produce symptoms. Removal of FBs is
      not an infrequent challenge for upper gastrointestinal endoscopy. The aim of this
      study is to elicit our experience in a 5-year period in dealing with FBs in the
      upper gastrointestinal tract using upper endoscopy. METHODS: This retrospective
      study was conducted at Zagazig University Hospitals, Egypt, over a 5-year period.
      We reviewed all patients' files with full notations on age, sex, type of FB and
      its anatomical location, treatments, and outcomes (complications, success rates,
      and mortalities). Patients with incomplete files and those with FBs not
      identified at the endoscopic examination were excluded. RESULTS: A total of 45
      patients were identified. Their ages ranged from 6 months to 102 years. Slight
      male predominance was noticed (53.3%). The most frequent presentation was a
      history of FB ingestion without any associated manifestations (44.4%). Coins were
      the most commonly encountered FBs (14/45). Esophagus was the most common site of
      trapping (27/45). The overall success rate was 95.6% (43/45). Upper endoscopy
      successfully resolved the problem by either FB removal (41/43) or dislodgment of
      the impacted fleshy meat to the stomach (2/43). Two cases were referred for
      surgical removal. The rate of complications was 6.7%. Furthermore, no mortalities
      due to FB ingestion or removal had been reported throughout the study.
      CONCLUSION: Our experience with FB removal emphasizes its importance and ease
      when performed by experienced hands, at well-equipped endoscopy units, and under
      conscious sedation in most cases, with high success rates and minor
      complications.

PMID- 25053890
TI  - Optimal management of complications associated with achondroplasia.
AB  - Achondroplasia is the most common form of skeletal dysplasia, resulting in
      disproportionate short stature, and affects over 250,000 people worldwide.
      Individuals with achondroplasia demonstrate a number of well-recognized
      anatomical features that impact on growth and development, with a complex array
      of medical issues that are best managed through a multidisciplinary team
      approach. The complexity of this presentation, whereby individual impairments may
      impact upon multiple activity and participation areas, requires consideration and
      discussion under a broad framework to gain a more thorough understanding of the
      experience of this condition for individuals with achondroplasia. This paper
      examines the general literature and research evidence on the medical and health
      aspects of individuals with achondroplasia and presents a pictorial model of
      achondroplasia based on The International Classification of Functioning,
      Disability, and Health (ICF). An expanded model of the ICF will be used to review
      and present the current literature pertaining to the musculoskeletal,
      neurological, cardiorespiratory, and ear, nose, and throat impairments and
      complications across the lifespan, with discussion on the impact of these
      impairments upon activity and participation performance. Further research is
      required to fully identify factors influencing participation and to help develop
      strategies to address these factors. 

PMID- 25053891
TI  - Identification of trisomy 18, trisomy 13, and Down syndrome from maternal plasma.
AB  - Current prenatal diagnosis for fetal aneuploidies (including trisomy 21 [T21])
      generally relies on an initial biochemical serum-based noninvasive prenatal
      testing (NIPT) after which women who are deemed to be at high risk are offered an
      invasive confirmatory test (amniocentesis or chorionic villi sampling for a fetal
      karyotype), which is associated with a risk of fetal miscarriage. Recently,
      genomics-based NIPT (gNIPT) was proposed for the analysis of fetal genomic DNA
      circulating in maternal blood. The diffusion of this technology in routine
      prenatal care could be a major breakthrough in prenatal diagnosis, since initial
      research studies suggest that this novel approach could be very effective and
      could reduce substantially the number of invasive procedures. However, the
      limitations of gNIPT may be underappreciated. In this review, we examine
      currently published literature on gNIPT to highlight advantages and limitations.
      At this time, the performance of gNIPT is relatively well-documented only in high
      risk pregnancies for T21 and trisomy 18. This additional screening test may be an
      option for women classified as high-risk of aneuploidy who wish to avoid invasive
      diagnostic tests, but it is crucial that providers carefully counsel patients
      about the test's advantages and limitations. The gNIPT is currently not
      recommended as a first-tier prenatal screening test for T21. Since gNIPT is not
      considered as a diagnostic test, a positive gNIPT result should always be
      confirmed by an invasive test, such as amniocentesis or chorionic villus
      sampling. Validation studies are needed to optimally introduce this technology
      into the existing routine workflow of prenatal care. 

PMID- 25053893
TI  - Accelerated atherosclerosis after renal transplantation: an unsuspected cause of
      uncontrolled hypertension.

PMID- 25053892
TI  - Disease-modifying genes and monogenic disorders: experience in cystic fibrosis.
AB  - The mechanisms responsible for the determination of phenotypes are still not well
      understood; however, it has become apparent that modifier genes must play a
      considerable role in the phenotypic heterogeneity of Mendelian disorders.
      Significant advances in genetic technologies and molecular medicine allow huge
      amounts of information to be generated from individual samples within a
      reasonable time frame. This review focuses on the role of modifier genes using
      the example of cystic fibrosis, the most common lethal autosomal recessive
      disorder in the white population, and discusses the advantages and limitations of
      candidate gene approaches versus genome-wide association studies. Moreover, the
      implications of modifier gene research for other monogenic disorders, as well as
      its significance for diagnostic, prognostic, and therapeutic approaches are
      summarized. Increasing insight into modifying mechanisms opens up new
      perspectives, dispelling the idea of genetic disorders being caused by one single
      gene. 

PMID- 25053894
TI  - Empirical comparison of four baseline covariate adjustment methods in analysis of
      continuous outcomes in randomized controlled trials.
AB  - BACKGROUND: Although seemingly straightforward, the statistical comparison of a
      continuous variable in a randomized controlled trial that has both a pre- and
      posttreatment score presents an interesting challenge for trialists. We present
      here empirical application of four statistical methods (posttreatment scores with
      analysis of variance, analysis of covariance, change in scores, and percent
      change in scores), using data from a randomized controlled trial of postoperative
      pain in patients following total joint arthroplasty (the Morphine COnsumption in
      Joint Replacement Patients, With and Without GaBapentin Treatment, a RandomIzed
      ControlLEd Study [MOBILE] trials). METHODS: Analysis of covariance (ANCOVA) was
      used to adjust for baseline measures and to provide an unbiased estimate of the
      mean group difference of the 1-year postoperative knee flexion scores in knee
      arthroplasty patients. Robustness tests were done by comparing ANCOVA with three
      comparative methods: the posttreatment scores, change in scores, and percentage
      change from baseline. RESULTS: All four methods showed similar direction of
      effect; however, ANCOVA (-3.9; 95% confidence interval [CI]: -9.5, 1.6; P=0.15)
      and the posttreatment score (-4.3; 95% CI: -9.8, 1.2; P=0.12) method provided the
      highest precision of estimate compared with the change score (-3.0; 95% CI: -9.9,
      3.8; P=0.38) and percent change (-0.019; 95% CI: -0.087, 0.050; P=0.58).
      CONCLUSION: ANCOVA, through both simulation and empirical studies, provides the
      best statistical estimation for analyzing continuous outcomes requiring covariate
      adjustment. Our empirical findings support the use of ANCOVA as an optimal method
      in both design and analysis of trials with a continuous primary outcome.

PMID- 25053895
TI  - Fundal height growth curve patterns of pregnant women with term low birth weight
      infants.
AB  - PURPOSE: To investigate the patterns of fundal height (FH) growth curve in
      pregnant women with term low birth weight (LBW) infants compared with the
      standard FH growth curve for Thai women. SUBJECTS AND METHODS: A retrospective
      study was conducted at the four governmental general hospitals in the northern
      part of Thailand between 2009 and 2011. All data were obtained from antenatal
      records and labor registry. Serial FH measurements in centimeters of 75 pregnant
      women with term LBW infants were plotted against the standard FH growth curve for
      Thai women throughout pregnancy. RESULTS: SIX PATTERNS OF THE FH GROWTH CURVE
      WERE SUMMARIZED: pattern I: FH below or around the tenth percentile throughout
      pregnancy (n=17, 22.7%); pattern II: FH below normal in early pregnancy, caught
      up with normal, then decelerated or stagnant (n=19, 25.3%); pattern III: FH
      normal in early pregnancy, then decelerated or stagnant (n=17, 22.7%); pattern
      IV: FH normal in early pregnancy, decelerated or stagnant, then caught up to
      normal (n=6, 8.0%); pattern V: FH normal throughout pregnancy except for the last
      visit (n=6, 8.0%); and pattern VI: FH normal throughout pregnancy (n=10, 13.3%).
      CONCLUSION: Patterns I-V may be used to recognize women who are likely to deliver
      term LBW infants from early pregnancy, during pregnancy, and on the day of
      admission for labor. Ultrasound evaluation is still recommended in cases with
      known risk factors that might be undetectable by FH, or in cases where FH
      measurement may be inaccurate.

PMID- 25053897
TI  - Deficiency areas in decision making in undergraduate medical students.
AB  - BACKGROUND: In family medicine, decisions can be difficult due to the early
      presentation of often poorly developed symptoms or the presentation of
      undifferentiated conditions that require competencies unique to family medicine,
      such as; primary care management, specific problem-solving skills, and a
      comprehensive and holistic approach to be taught to medical students. PURPOSE:
      The aim of this study was to assess the decision-making process covering all
      theoretical aspects of family practice consultation and to recognize possible
      areas of deficiency in undergraduate medical students. MATERIALS AND METHODS:
      This was a cross-sectional, observational study performed at the Medical School
      of the University of Maribor in Slovenia. The study population consisted of 159
      fourth-year medical students attending a family medicine class. The main outcome
      measure was the scores of the students' written reports on solving the virtual
      clinical case. An assessment tool consisted of ten items that could be graded on
      a 5-point Likert scale. RESULTS: The final sample consisted of 147 (92.5%)
      student reports. There were 95 (64.6%) female students in the sample. The mean
      total score on the assessment scale was 35.1+/-7.0 points of a maximum 50 points.
      Students scored higher in the initial assessment items and lower in the patient
      education/involvement items. Female students scored significantly higher in terms
      of total assessment score and in terms of initial assessment and patient
      education/involvement. CONCLUSION: Undergraduate medical education should devote
      more time to teaching a comprehensive approach to consultation, especially
      modification of the health behavior of patients and opportunistic health
      promotion to patients. Possible sex differences in students' performance should
      be further evaluated.

PMID- 25053898
TI  - Readout-segmented echo-planar imaging in diffusion-weighted mr imaging in breast
      cancer: comparison with single-shot echo-planar imaging in image quality.
AB  - OBJECTIVE: The purpose of this study was to compare the image quality of standard
      single-shot echo-planar imaging (ss-EPI) and that of readout-segmented EPI (rs
      EPI) in patients with breast cancer. MATERIALS AND METHODS: Seventy-one patients
      with 74 breast cancers underwent both ss-EPI and rs-EPI. For qualitative
      comparison of image quality, three readers independently assessed the two sets of
      diffusion-weighted (DW) images. To evaluate geometric distortion, a comparison
      was made between lesion lengths derived from contrast enhanced MR (CE-MR) images
      and those obtained from the corresponding DW images. For assessment of image
      parameters, signal-to-noise ratio (SNR), lesion contrast, and contrast-to-noise
      ratio (CNR) were calculated. RESULTS: The rs-EPI was superior to ss-EPI in most
      criteria regarding the qualitative image quality. Anatomical structure
      distinction, delineation of the lesion, ghosting artifact, and overall image
      quality were significantly better in rs-EPI. Regarding the geometric distortion,
      lesion length on ss-EPI was significantly different from that of CE-MR, whereas
      there were no significant differences between CE-MR and rs-EPI. The rs-EPI was
      superior to ss-EPI in SNR and CNR. CONCLUSION: Readout-segmented EPI is superior
      to ss-EPI in the aspect of image quality in DW MR imaging of the breast.

PMID- 25053900
TI  - Extra-mammary findings detected on breast magnetic resonance imaging: a pictorial
      essay.
AB  - Magnetic resonance imaging (MRI) of the breast is used for various indications.
      Contrary to computed tomography as a staging tool, breast MRI focuses on the
      breast parenchyma and axilla. In spite of narrow field of view, many structures
      such as the anterior portion of the lungs, mediastinum, bony structures and the
      liver are included which should not be neglected because the abnormalities
      detected on the above structures may influence the staging and provide a clue to
      systemic metastasis, which results in the change of treatment strategy. The
      purpose of this pictorial essay was to review the unexpected extra-mammary
      findings seen on the preoperative breast MRI. 

PMID- 25053899
TI  - Trastuzumab-conjugated liposome-coated fluorescent magnetic nanoparticles to
      target breast cancer.
AB  - OBJECTIVE: To synthesize mesoporous silica-core-shell magnetic nanoparticles
      (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their
      stability, allow them to be used in any buffer solution, and to produce
      trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in
      vitro for the targeting of breast cancer. MATERIALS AND METHODS: The
      physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of
      size, morphological features, and in vitro safety. The multimodal imaging
      properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed
      with both in vitro fluorescence and MR imaging. The specific targeting ability of
      trastuzumab (Her2/neu antibody, Herceptin(r))-conjugated Lipo[MNP@m-SiO2] for
      Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR
      imaging. RESULTS: We obtained uniformly-sized and evenly distributed Lipo[MNP@m
      SiO2] that demonstrated biological stability, while not disrupting cell
      viability. Her2/neu-positive breast cancer cell targeting by trastuzumab
      conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging.
      CONCLUSION: Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool
      for targeted drug delivery in Her2/neu-positive breast cancer.

PMID- 25053901
TI  - Effects of dual-energy CT with non-linear blending on abdominal CT angiography.
AB  - OBJECTIVE: To determine whether non-linear blending technique for arterial-phase
      dual-energy abdominal CT angiography (CTA) could improve image quality compared
      to the linear blending technique and conventional 120 kVp imaging. MATERIALS AND
      METHODS: This study included 118 patients who had accepted dual-energy abdominal
      CTA in the arterial phase. They were assigned to Sn140/80 kVp protocol (protocol
      A, n = 40) if body mass index (BMI) < 25 or Sn140/100 kVp protocol (protocol B, n
      = 41) if BMI >= 25. Non-linear blending images and linear blending images with a
      weighting factor of 0.5 in each protocol were generated and compared with the
      conventional 120 kVp images (protocol C, n = 37). The abdominal vascular
      enhancements, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio
      (CNR) and radiation dose were assessed. Statistical analysis was performed using
      one-way analysis of variance test, independent t test, Mann-Whitney U test, and
      Kruskal-Wallis test. RESULTS: Mean vascular attenuation, CNR, SNR and subjective
      image quality score for the non-linear blending images in each protocol were all
      higher compared to the corresponding linear blending images and 120 kVp images (p
      values ranging from < 0.001 to 0.007) except for when compared to non-linear
      blending images for protocol B and 120 kVp images in CNR and SNR. No significant
      differences were found in image noise among the three kinds of images and the
      same kind of images in different protocols, but the lowest radiation dose was
      shown in protocol A. CONCLUSION: Non-linear blending technique of dual-energy CT
      can improve the image quality of arterial-phase abdominal CTA, especially with
      the Sn140/80 kVp scanning.

PMID- 25053902
TI  - Clinical and radiologic review of uncommon cause of profound iron deficiency
      anemia: median arcuate ligament syndrome.
AB  - Median arcuate ligament syndrome is an anatomic and clinical entity characterized
      by dynamic compression of the proximal celiac artery by the median arcuate
      ligament, which leads to postprandial epigastric pain, vomiting, and weight loss.
      These symptoms are usually nonspecific and are easily misdiagnosed as functional
      dyspepsia, peptic ulcer disease, or gastropathy. In this report, we presented a
      72-year-old male patient with celiac artery compression syndrome causing
      recurrent abdominal pain associated with gastric ulcer and iron deficiency
      anemia. This association is relatively uncommon and therefore not well
      determined. In addition, we reported the CT angiography findings and three
      dimensional reconstructions of this rare case. 

PMID- 25053903
TI  - Pulmonary bone cement embolism: CT angiographic evaluation with material
      decomposition using gemstone spectral imaging.
AB  - We report a case of pulmonary bone cement embolism in a female who presented with
      dyspnea following multiple sessions of vertebroplasty. She underwent spectral CT
      pulmonary angiography and the diagnosis was made based on enhanced visualization
      of radiopaque cement material in the pulmonary arteries and a corresponding
      decrease in the parenchymal iodine content. Here, we describe the CT angiography
      findings of bone cement embolism with special emphasis on the potential benefits
      of spectral imaging, providing additional information on the material
      composition. 

PMID- 25053904
TI  - Serial micro-CT assessment of the therapeutic effects of rosiglitazone in a
      bleomycin-induced lung fibrosis mouse model.
AB  - OBJECTIVE: The aim of this study was to assess the therapeutic effects of
      rosiglitazone with serial micro-CT findings before and after rosiglitazone
      administration in a lung fibrosis mouse model induced with bleomycin. MATERIALS
      AND METHODS: We instilled the bleomycin solution directly into the trachea in
      twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice
      were closely observed for 3 weeks and then all mice were scanned using micro-CT
      without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days
      21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with
      rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the
      rosiglitazone treatment completion. We assessed the abnormal CT findings (ground
      glass attenuation, consolidation, bronchiectasis, reticular opacity, and
      honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed
      ranked test. The micro-CT findings were correlated with the histopathologic
      results. RESULTS: One out of nine (11.1%) mice improved completely. In terms of
      consolidation, all mice (100%) showed marked decrease from 3.1 +/- 1.4 at 3 weeks
      to 0.9 +/- 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6,
      66.7%), mild reticular opacity (n = 7, 77.8%) and mild honeycomb patterns (n = 3,
      33.3%) appeared. CONCLUSION: A serial micro-CT enables the evaluation of drug
      effects in a lung fibrosis mouse model.

PMID- 25053905
TI  - Contrast-induced nephropathy in patients undergoing intravenous contrast-enhanced
      computed tomography in Korea: a multi-institutional study in 101487 patients.
AB  - OBJECTIVE: To evaluate the prevalence of known risk factors for contrast-induced
      nephropathy (CIN) and their association with the actual occurrence of CIN in
      patients undergoing intravenous contrast-enhanced computed tomography (CECT) in
      Korea. MATERIALS AND METHODS: Patients who underwent CECT in 2008 were identified
      in the electronic medical records of 16 tertiary hospitals of Korea. Data on
      demographics, comorbidities, prescriptions and laboratory test results of
      patients were collected following a standard data extraction protocol. The
      baseline renal function was assessed using the estimated glomerular filtration
      rate (eGFR). We identified the prevalence of risk factors along the eGFR strata
      and evaluated their influence on the incidence of CIN, defined as a 0.5 mg/dL or
      25% increase in serum creatinine after CECT. RESULTS: Of 432425 CECT examinations
      in 272136 patients, 140838 examinations in 101487 patients met the eligibility
      criteria for analysis. The mean age of the participants was 57.9 +/- 15.5 years;
      25.1% of the patients were older than 70 years. The prevalence of diabetes
      mellitus was 11.9%, of hypertension 13.7%, of gout 0.55% and of heart failure was
      1.7%. Preventive measures were used in 40238 CECT examinations (28.6%). The
      prevalence of risk factors and use of preventive measures increased as the renal
      function became worse. A CIN was occurred after 3103 (2.2%) CECT examinations,
      revealing a significant association with decreased eGFR, diabetes mellitus, and
      congestive heart failure after adjustment. CONCLUSION: Risk factors for CIN are
      prevalent among the patients undergoing CECT. Preventive measures were seemingly
      underutilized and a system is needed to improve preventive care.

PMID- 25053906
TI  - Transcatheter arterial chemoembolization for infiltrative hepatocellular
      carcinoma: clinical safety and efficacy and factors influencing patient survival.
AB  - OBJECTIVE: To evaluate the safety and efficacy of transcatheter arterial
      chemoembolization (TACE) in patients with infiltrative hepatocellular carcinoma
      (HCC) and to identify the prognostic factors associated with patient survival.
      MATERIALS AND METHODS: Fifty two patients who underwent TACE for infiltrative HCC
      were evaluated between 2007 and 2010. The maximum diameter of the tumors ranged
      from 7 cm to 22 cm (median 15 cm). Of 46 infiltrative HCC patients with portal
      vein tumor thrombosis, 32 patients received adjuvant radiation therapy for portal
      vein tumor thrombosis after TACE. RESULTS: The tumor response by European
      Association for the Study of the Liver criteria was partial in 18%, stable in
      47%, and progressive in 35% of the patients. The median survival time was 5.7
      months (Kaplan-Meier analysis). The survival rates were 48% at six months, 25% at
      one year, and 12% at two years. In the multivariable Cox regression analysis,
      Child-Pugh class (p = 0.02), adjuvant radiotherapy (p = 0.003) and tumor response
      after TACE (p = 0.004) were significant factors associated with patient survival.
      Major complications occurred in nine patients. The major complication rate was
      significantly higher in patients with Child-Pugh B than in patients with Child
      Pugh A (p = 0.049, chi(2) test). CONCLUSION: Transcatheter arterial
      chemoembolization can be a safe treatment option in infiltrative HCC patients
      with Child Pugh class A. Child Pugh class A, radiotherapy for portal vein tumor
      thrombosis after TACE and tumor response are good prognostic factors for an
      increased survival after TACE in patients with infiltrative HCCs.

PMID- 25053907
TI  - Safety and efficacy of transarterial nephrectomy as an alternative to surgical
      nephrectomy.
AB  - OBJECTIVE: To evaluate the safety and efficacy of transarterial nephrectomy,
      i.e., complete renal artery embolization, as an alternative to surgical
      nephrectomy. MATERIALS AND METHODS: This retrospective study included 11 patients
      who underwent transarterial nephrectomy due to a high risk of surgical
      nephrectomy or their refusal to undergo surgery during the period from April 2002
      to February 2013. Medical records and radiographic images were reviewed
      retrospectively to collect information regarding underlying etiologies, clinical
      presentations and embolization outcomes. RESULTS: The underlying etiologies for
      transarterial nephrectomy included recurrent hematuria (chronic transplant
      rejection [n = 3], arteriovenous malformation or fistula [n = 3], angiomyolipoma
      [n = 1], or end-stage renal disease [n = 1]), inoperable renal or ureteral injury
      (n = 2), and ectopic kidney with urinary incontinence (n = 1). The technical
      success rate was 100%, while clinical success was achieved in eight patients
      (72.7%). Subsequent surgical nephrectomy was required for three patients due to
      an incomplete nephrectomy effect (n = 2) or necrotic pyelonephritis (n = 1).
      Procedure-related complications were post-infarction syndrome in one patient and
      necrotic pyelonephritis in another patient. Of four patients with follow-up CT,
      four showed renal atrophy and two showed partial renal enhancement. No patient
      developed a procedure-related hypertension. CONCLUSION: Transarterial nephrectomy
      may be a safe and effective alternative to surgical nephrectomy in patients with
      high operative risks.

PMID- 25053908
TI  - Fluoroscopy-guided endovenous sclerotherapy using a microcatheter prior to
      endovenous laser ablation: comparison between liquid and foam sclerotherapy for
      varicose tributaries.
AB  - OBJECTIVE: To compare the efficacy and adverse effects of endovenous foam
      sclerotherapy (EFS) and liquid sclerotherapy (ELS) using a microcatheter for the
      treatment of varicose tributaries. MATERIALS AND METHODS: From December 2007 to
      January 2009, patients with venous reflux in the saphenous vein were enrolled.
      The foam or liquid sclerosant was injected through a microcatheter just before
      endovenous laser ablation (EVLA). Patients were evaluated for the technical
      success, clinical success, and procedure-related complications during the
      procedure and follow-up visits. RESULTS: A total of 94 limbs were included: 48
      limbs (great saphenous vein [GSV], 35; small saphenous vein [SSV], 13) were
      managed using EFS and EVLA (foam group; FG), and 46 limbs (GSV, 37; SSV, 9) were
      treated by ELS and EVLA (liquid group; LG). Varicose tributaries demonstrated
      complete sclerosis in 92.7% with FG and in 71.8% with LG (p = 0.014). Bruising
      (78.7% in FG vs. 73.2% in LG, p > 0.05), pain or tenderness (75.6% in FG vs.
      51.2% in LG, p = 0.0237) were noted. Hyperpigmentation (51.2% in FG vs. 46.2% in
      LG, p > 0.05) was found. CONCLUSION: Endovenous foam sclerotherapy using a
      microcatheter is more effective than ELS for eliminating remnant varicose
      tributaries prior to EVLA. However, EFS is more commonly associated with local
      complications such as pain or tenderness than ELS. Furthermore, both techniques
      seem to prolong the duration of hyperpigmentation along with higher costs.

PMID- 25053909
TI  - Percutaneous radiologic gastrostomy using the one-anchor technique in patients
      after partial gastrectomy.
AB  - OBJECTIVE: The purpose of our study was to assess the feasibility of performing
      percutaneous radiologic gastrostomy (PRG) in patients who had undergone partial
      gastrectomy and to evaluate factors associated with technical success. MATERIALS
      AND METHODS: Nineteen patients after partial gastrectomy, who were referred for
      PRG between April 2006 and April 2012, were retrospectively analyzed. The remnant
      stomach was punctured using a 21-gauge Chiba-needle. A single anchor was used for
      the gastropexy and a 12-Fr or 14-Fr gastrostomy tube was inserted. Data were
      collected regarding the technical success, procedure time, and presence of any
      complications. Univariable analyses were performed to determine the factors
      related to the technical success. RESULTS: Percutaneous radiologic gastrostomy
      was technically successful in 10 patients (53%), while a failed attempt and
      failure without an attempt were observed in 5 (26%) and 4 (21%) patients,
      respectively. Percutaneous radiologic jejunostomy was successfully performed in 9
      patients who experienced technical failure. In the 10 successful PRG cases, the
      mean procedure time was 6.35 minutes. Major complications occurred in 2 patients,
      tube passage through the liver and pneumoperitonum in one and severe hemorrhage
      in the other. The technical success rate was higher in patients with Billroth I
      gastrectomy (100%, 6/6) than in patients with Billroth II gastrectomy (31%, 4/13)
      (p = 0.011). CONCLUSION: Percutaneous radiologic gastrostomy can be successfully
      performed using the one-anchor technique in approximately half of the patients
      after partial gastrectomy.

PMID- 25053910
TI  - Incidence and risk factors of infectious complications related to implantable
      venous-access ports.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and risk
      factors of infections associated with implantable venous access ports (IVAPs).
      MATERIALS AND METHODS: From August 2003 through November 2011, 1747 IVAPs were
      placed in our interventional radiology suite. One hundred forty four IVAPs were
      inserted in patients with hematologic malignancy and 1603 IVAPs in patients with
      solid tumors. Among them, 40 ports (23 women and 17 men; mean age, 57.1 years;
      range, 13-83) were removed to treat port-related infections. We evaluated the
      incidence of port-related infection, patient characteristics, bacteriologic data,
      and patient progress. Univariable analyses (t test, chi-square test, and Fisher's
      exact test) and multiple logistic regression analyses were used to determine the
      risk factors for IVAP related infection. RESULTS: Overall, 40 (2.3%) of 1747
      ports were removed for symptoms of infection with an incidence rate of 0.067
      events/1000 catheter-days. According to the univariable study, the incidences of
      infection were seemingly higher in the patients who received the procedure during
      inpatient treatment (p = 0.016), the patients with hematologic malignancy (p =
      0.041), and the patients receiving palliative chemotherapy (p = 0.022). From the
      multiple binary logistic regression, the adjusted odds ratios of infection in
      patients with hematologic malignancies and those receiving palliative
      chemotherapy were 7.769 (p = 0.001) and 4.863 (p = 0.003), respectively.
      Microorganisms were isolated from 26 (65%) blood samples, and two of the most
      causative organisms were found to be Staphylococcus (n = 10) and Candida species
      (n = 7). CONCLUSION: The underlying hematologic malignancy and the state of
      receiving palliative chemotherapy were the independent risk factors of IVAP
      related infection.

PMID- 25053911
TI  - Visual MRI grading system to evaluate atrophy of the supraspinatus muscle.
AB  - OBJECTIVE: To investigate the interobserver reproducibility and diagnostic
      feasibility of a visual grading system for assessing atrophy of the supraspinatus
      muscle on magnetic resonance imaging (MRI). MATERIALS AND METHODS: Three
      independent radiologists retrospectively evaluated the occupying ratio of the
      supraspinatus muscle in the supraspinatus fossa on 192 shoulder MRI examinations
      in 188 patients using a 3-point visual grading system (1, >= 60%; 2, 30-59%; 3, <
      30%) on oblique sagittal T1-weighted images. The inter-reader agreement and the
      agreement with the reference standard (3-point grades according to absolute
      occupying ratio values quantitatively measured by directly contouring the muscles
      on MRI) were analyzed using weighted kappa. The visual grading was applied by a
      single reader to a group of 100 consecutive patients who had undergone rotator
      cuff repair to retrospectively determine the association between the visual
      grades at preoperative state and postsurgical occurrences of retear. RESULTS: The
      inter-reader weighted kappa value for the visual grading was 0.74 when averaged
      across three reader pairs (0.70-0.77 for individual reader pairs). The weighted
      kappa value between the visual grading and the reference standard ranged from
      0.75 to 0.83. There was a significant difference in retear rates of the rotator
      cuff between the 3 visual grades of supraspinatus muscle atrophy on MRI in
      univariable analysis (p < 0.001), but not in multivariable analysis (p = 0.026).
      CONCLUSION: The 3-point visual grading system may be a feasible method to assess
      the severity of supraspinatus muscle atrophy on MRI and assist in the clinical
      management of patients with rotator cuff tear.

PMID- 25053912
TI  - Anatomy, variants, and pathologies of the superior glenohumeral ligament:
      magnetic resonance imaging with three-dimensional volumetric interpolated breath
      hold examination sequence and conventional magnetic resonance arthrography.
AB  - The purpose of this review was to demonstrate magnetic resonance (MR)
      arthrography findings of anatomy, variants, and pathologic conditions of the
      superior glenohumeral ligament (SGHL). This review also demonstrates the
      applicability of a new MR arthrography sequence in the anterosuperior portion of
      the glenohumeral joint. The SGHL is a very important anatomical structure in the
      rotator interval that is responsible for stabilizing the long head of the biceps
      tendon. Therefore, a torn SGHL can result in pain and instability. Observation of
      the SGHL is difficult when using conventional MR imaging, because the ligament
      may be poorly visualized. Shoulder MR arthrography is the most accurately
      established imaging technique for identifying pathologies of the SGHL and
      associated structures. The use of three dimensional (3D) volumetric interpolated
      breath-hold examination (VIBE) sequences produces thinner image slices and
      enables a higher in-plane resolution than conventional MR arthrography sequences.
      Therefore, shoulder MR arthrography using 3D VIBE sequences may contribute to
      evaluating of the smaller intraarticular structures such as the SGHL. 

PMID- 25053913
TI  - Altered activity and functional connectivity of superior temporal gyri in anxiety
      disorders: a functional magnetic resonance imaging study.
AB  - OBJECTIVE: The prior functional MRI studies have demonstrated significantly
      abnormal activity in the bilateral superior temporal gyrus (STG) of anxiety
      patients. The purpose of the current investigation was to determine whether the
      abnormal activity in these regions was related to a loss of functional
      connectivity between these regions. MATERIALS AND METHODS: Ten healthy controls
      and 10 anxiety patients underwent noninvasive fMRI while actively listening to
      emotionally neutral words alternated by silence (Task 1) or threat-related words
      (Task 2). The participants were instructed to silently make a judgment of each
      word's valence (i.e., unpleasant, pleasant, or neutral). A coherence analysis was
      applied to the functional MRI data to examine the functional connectivity between
      the left and the right STG, which was selected as the primary region of interest
      on the basis of our prior results. RESULTS: The data demonstrated that the
      anxiety patients exhibited significantly increased activation in the bilateral
      STG than the normal controls. The functional connectivity analysis indicated that
      the patient group showed significantly decreased degree of connectivity between
      the bilateral STG during processing Task 2 compared to Task 1 (t = 2.588, p =
      0.029). In addition, a significantly decreased connectivity was also observed in
      the patient group compared to the control group during processing Task 2 (t =
      2.810, p = 0.012). CONCLUSION: Anxiety patients may exhibit increased activity of
      the STG but decreased functional connectivity between the left and right STG,
      which may reflect the underlying neural abnormality of anxiety disorder, and this
      will provide new insights into this disease.

PMID- 25053914
TI  - Hot-clot artifacts in the lung parenchyma on F-18 fluorodeoxyglucose positron
      emission tomography/CT due to faulty injection techniques: two case reports.
AB  - F-18-fluorodeoxyglucose (FDG) positron emission tomography/CT is an important
      whole-body imaging tool in the oncology and widely utilized to stage and restage
      various malignancies. The findings of significant focal accumulation of FDG in
      the lung parenchyma in the absence of corresponding CT abnormalities are related
      to the lung microembolism and known as hot-clot artifacts. Herein we present two
      cases with focal FDG uptake in the lung parenchyma with no structural lesions on
      the CT scan and discuss the possible mechanisms. 

PMID- 25053915
TI  - Happle-Tinschert syndrome: report of a case with hemimegalencephaly.
AB  - Happle-Tinschert syndrome is a disorder causing unilateral segmentally arranged
      basaloid follicular hamartomas of the skin associated with ipsilateral osseous,
      dental and cerebral abnormalities including tumors. Although a case with
      hemimegalencephaly was previously described, this is the first report of Happle
      Tinschert syndrome with discrepant short left leg, ipsilateral skin lesions,
      hemimegalencephaly and frontal polymicrogyria. 

PMID- 25053916
TI  - Re: hemangiopericytoma of the greater omentum: a potential imaging pitfall and
      cause of repeatedly unsuccessful angiographic embolization.

PMID- 25053917
TI  - Re: communication between the cystic lesions of the liver and biliary tree: how
      can we evaluate efficiently and safely?

PMID- 25053918
TI  - Re: hepatocolic fistula: a potential complication following radiofrequency
      ablation of liver lesions in patients previously pancreaticoduodenectomized or
      cholecystectomized.

PMID- 25053919
TI  - mPing: The bursting transposon.
AB  - Though transposable elements (TEs) have been considered as an efficient source of
      evolution, it has never been possible to test this hypothesis because most of TE
      insertions had occurred millions of years ago, or because currently active TEs
      have very few copies in a host genome. However, mPing, the first active DNA
      transposon in rice, was revealed to hold a key to answer this question. mPing has
      attained high copy numbers and still retained very high activity in a traditional
      rice strain, which enabled direct observation of behavior and impact of a
      bursting TE. A comprehensive analysis of mPing insertion sites has revealed it
      avoids exons but prefers promoter regions and thus moderately affects
      transcription of neighboring genes. Some of the mPing insertions have introduced
      possibly useful expression profile to adjacent genes that indicated TE's
      potential in de novo formation of gene regulatory network. 

PMID- 25053920
TI  - Predictors of emergency room visits or acute hospital admissions prior to death
      among hospice palliative care clients in Ontario: a retrospective cohort study.
AB  - BACKGROUND: Hospice palliative care (HPC) is a philosophy of care that aims to
      relieve suffering and improve the quality of life for clients with life
      threatening illnesses or end of life issues. The goals of HPC are not only to
      ameliorate clients' symptoms but also to reduce unneeded or unwanted medical
      interventions such as emergency room visits or hospitalizations (ERVH). Hospitals
      are considered a setting ill-prepared for end of life issues; therefore, use of
      such acute care services has to be considered an indicator of poor quality end of
      life care. This study examines predictors of ERVH prior to death among HPC home
      care clients. METHODS: A retrospective cohort study of a sample of 764 HPC home
      care clients who received services from a community care access centre (CCAC) in
      southern Ontario, Canada. All clients were assessed using the Resident Assessment
      Instrument for Palliative Care (interRAI PC) as part of normal clinical practice
      between April 2008 and July 2010. The Andersen-Newman framework for health
      service utilization was used as a conceptual model for the basis of this study.
      Logistic regression and Cox regression analyses were carried out to identify
      predictors of ERVH. RESULTS: Half of the HPC clients had at least one or more
      ERVH (n = 399, 52.2%). Wish to die at home (OR = 0.54) and advanced care
      directives (OR = 0.39) were protective against ERVH. Unstable health (OR = 0.70)
      was also associated with reduced probability, while infections such as prior
      urinary tract infections (OR = 2.54) increased the likelihood of ERVH. Clients
      with increased use of formal services had reduced probability of ERVH (OR =
      0.55). CONCLUSIONS: Findings of this study suggest that predisposing
      characteristics are nearly as important as need variables in determining ERVH
      among HPC clients, which challenges the assumption that need variables are the
      most important determinants of ERVH. Ongoing assessment of HPC clients is
      essential in reducing ERVH, as reassessments at specified intervals will allow
      care and service plans to be adjusted with clients' changing health needs and end
      of life preferences.

PMID- 25053921
TI  - Factors that act as facilitators and barriers to nurse leaders' participation in
      health policy development.
AB  - BACKGROUND: Health policies impact on nursing profession and health care. Nurses'
      involvement in health policy development ensures that health care is safe, of a
      high quality, accessible and affordable. Numerous factors influence nurse
      leaders' ability to be politically active in influencing health policy
      development. These factors can be facilitators or barriers to their
      participation. There is scant research evidence from Eastern African region that
      draws attention to this topic. This paper reports part of the larger study. The
      objectives reported in this paper were those aimed to: build consensus on factors
      that act as facilitators and barriers to nurse leaders' participation in health
      policy development in Kenya, Uganda and Tanzania. METHODS: A DELPHI SURVEY WAS
      APPLIED WHICH INCLUDED: expert panelists, iterative rounds, statistical analysis,
      and consensus building. The expert panelists were purposively selected and
      included national nurse leaders in leadership positions in East Africa. Data
      collection was done, in three iterative rounds, and utilized a questionnaire with
      open and closed ended questions. 78 expert panelists were invited to participate
      in the study; the response rate was 47% of these 64.8% participated in the second
      round and of those 100% participated in the third round. Data analysis was done
      by examining the data for the most commonly occurring categories for the open
      ended questions and descriptive statistics for structured questions. RESULTS: The
      findings of the study indicate that both facilitators and barriers exist. The
      former include: being involved in health policy development, having knowledge and
      skills, enhancing the image of nursing and enabling structures and processes. The
      latter include: lack of involvement, negative image of nursing and structures and
      processes which exclude them. CONCLUSION: There is a window of opportunity to
      enhance national nurse leaders' participation in health policy development. Nurse
      leaders have a key role in mentoring, supporting and developing future nurse
      policy makers.

PMID- 25053922
TI  - Heat shock protein 70 down-regulates the production of toll-like receptor-induced
      pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock
      element-binding factor-dependent mechanism.
AB  - BACKGROUND: Heat shock protein 70 (Hsp70) is an intracellular chaperone protein
      with regulatory and cytoprotective functions. Hsp70 can also be found in the
      extracellular milieu, as a result of active secretion or passive release from
      damaged cells. The role of extracellular Hsp70 is not fully understood. Some
      studies report that it activates monocytes, macrophages and dendritic cells
      through innate immune receptors (such as Toll-like receptors, TLRs), while others
      report that Hsp70 is a negative regulator of the inflammatory response. In order
      to address this apparent inconsistency, in this study we evaluated the response
      of human monocytes to a highly purified recombinant Hsp70. METHODS: Human
      peripheral blood monocytes were stimulated with Hsp70, alone or in combination
      with TLR agonists. Cytokines were quantified in culture supernatants, their mRNAs
      were measured by RT-PCR, and the binding of transcription factors was evaluated
      by electrophoretic mobility shift assay (EMSA). Kruskal-Wallis test or one-way or
      two-way ANOVA were used to analyze the data. RESULTS: The addition of Hsp70 to
      TLR-activated monocytes down-regulated TNF-alpha as well as IL-6 levels. This
      effect was independent of a physical interaction between Hsp70 and TLR agonists;
      instead it resulted of changes at the TNF-alpha gene expression level. The
      decrease in TNF-alpha expression correlated with the binding of HSF-1 (heat shock
      transcription factor 1, a transcription factor activated in response to Hsp70)
      and CHBF (constitutive HSE-binding factor) to the TNF-alpha gene promoter.
      CONCLUSION: Extracellular Hsp70 negatively regulates the production of pro
      inflammatory cytokines of monocytes exposed to TLR agonists and contributes to
      dampen the inflammatory response.

PMID- 25053923
TI  - A survey of steroid-related osteoporosis diagnosis, prevention and treatment
      practices of pediatric rheumatologists in North America.
AB  - BACKGROUND: The purpose of our study is to assess practices of North American
      pediatric rheumatologists regarding monitoring, prevention, and treatment of low
      bone mineral density (BMD) in children on long-term glucocorticoid treatment.
      Long-term glucocorticoid therapy is associated with accelerated bone loss.
      Children with JIA and lupus have low baseline BMD and incident vertebral
      fractures commonly occur in these groups of patients even after a relatively
      short period of time being on systemic glucocorticoids. There are no established
      guidelines for identification, prevention, and treatment of glucocorticoid
      induced bone loss in children. METHODS: A cross-sectional online survey was
      conducted with 199 physicians who were listed in the ACR database as practicing
      pediatric rheumatology in North America. RESULTS: 86 physicians (43%) responded;
      87% were board-certified in pediatric rheumatology. 95% used dual energy X-ray
      absorptiometry as their primary modality for assessing BMD. 79% "rarely" or
      "never" obtained a baseline BMD measurement prior to initiation of glucocorticoid
      therapy. 42% of respondents followed BMD annually. 93% "frequently" or "always"
      prescribed calcium for patients on long-term corticosteroid therapy; 81%
      "frequently" or "always" prescribed vitamin D. In patients diagnosed with
      osteoporosis, 35%-50 % of the practitioners "sometimes", "frequently" or "always"
      prescribed bisphosphonates. Bisphosphonates are prescribed at similar rates for
      male and female patients, and slightly more frequently for pubertal than for pre
      pubertal patients. 96% of respondents "rarely" or "never" prescribed calcitonin
      for patients on long-term glucocorticoid therapy; 92% "rarely" or "never"
      prescribe this medication for patients with known osteopenia or osteoporosis.
      CONCLUSIONS: Utilization of DXA in children on long-term corticosteroid therapy
      varies greatly among North American pediatric rheumatologists. Most respondents
      do not screen for low BMD on a regular basis despite acknowledging the risks of
      bone loss in this population. Broad consensus appears to be present among
      practitioners favoring the prescription of calcium and vitamin D for patients
      receiving long-term corticosteroid therapy. Relatively few respondents
      consistently recommend bisphosphonate therapy, even for patients with known low
      bone density; calcitonin is rarely used. These data underscore the need for
      studies to acquire specific data on bone loss, and its prevention and treatment
      in young patients on long-term glucocorticoid therapy.

PMID- 25053924
TI  - A cross-sectional electromyography assessment in linear scleroderma patients.
AB  - BACKGROUND: Muscle atrophy and asymmetric extremity growth is a common feature of
      linear scleroderma (LS). Extra-cutaneous features are also common and primary
      neurologic involvement, with sympathetic dysfunction, may have a pathogenic role
      in subcutaneous and muscle atrophy. The aim was investigate nerve conduction and
      muscle involvement by electromyography in pediatric patients with LS. METHODS: We
      conducted a retrospective review of LS pediatric patients who had regular follow
      up at a single pediatric center from 1997-2013. We selected participants if they
      had consistently good follow up and enrolled consecutive patients in the study.
      We examined LS photos as well as clinical, serological and imaging findings.
      Electromyograms (EMG) were performed with bilateral symmetric technique, using
      surface and needle electrodes, comparing the affected side with the contralateral
      side. Abnormal muscle activity was categorized as a myopathic or neurogenic
      pattern. RESULTS: Nine LS subjects were selected for EMG, 2 with Parry
      Romberg/Hemifacial Atrophy Syndrome, 7 linear scleroderma of an extremity and 2
      with mixed forms (linear and morphea). Electromyogram analysis indicated that all
      but one had asymmetric myopathic pattern in muscles underlying the linear
      streaks. Motor and sensory nerve conduction was also evaluated in upper and lower
      limbs and one presented a neurogenic pattern. Masticatory muscle testing showed a
      myopathic pattern in the atrophic face of 2 cases with head and face involvement.
      CONCLUSION: In our small series of LS patients, we found a surprising amount of
      muscle dysfunction by EMG. The muscle involvement may be possibly related to a
      secondary peripheral nerve involvement due to LS inflammation and fibrosis.
      Further collaborative studies to confirm these findings are needed.

PMID- 25053925
TI  - A randomised trial of pre-exercise meal composition on performance and muscle
      damage in well-trained basketball players.
AB  - BACKGROUND: Attenuating muscle damage is important to subsequent sports
      performance. It is possible that pre-exercise protein intake could influence
      markers of muscle damage and benefit performance, however, published research
      provides conflicting results. At present no study has investigated protein and
      carbohydrate (PRO/CHO) co-ingestion solely pre-exercise, nor prior to basketball
      specific exercise. The purpose of this study was to answer the research question;
      would pre-exercise protein intake enhance performance or attenuate muscle damage
      during a basketball simulation test? METHODS: Ten well-trained male basketball
      players consumed either carbohydrate (1 g . kg(-1) body mass) with protein (1 g .
      kg(-1) body mass), or carbohydrate alone (2 g . kg(-1) body mass) in a randomised
      cross- over design, 90 minutes before completing an 87-minute exercise protocol.
      RESULTS: The rise in creatine kinase (CK) from baseline to post-exercise was
      attenuated following PRO/CHO (56 +/- 13U . L(-1)) compared to carbohydrate (100
      +/- 10 U . L(-1)), (p = 0.018). Blood glucose was also higher during and post
      exercise following PRO/CHO (p < 0.050), as was free throw shooting accuracy in
      the fourth quarter (p = 0.027). Nausea during (p = 0.007) and post-(p = 0.039)
      exercise increased following PRO/CHO, as did cortisol post-exercise (p = 0.038).
      CONCLUSIONS: Results suggest that in well-trained basketball players, pre
      exercise PRO/CHO may attenuate the rise in CK, indicative of a decrease in muscle
      damage during exercise. However, unfamiliarity with the protein amount provided
      may have increased nausea during exercise, and this may have limited the ability
      to see an improvement in more performance measures.

PMID- 25053926
TI  - Fuzzy Logic Based Controller for a Grid-Connected Solid Oxide Fuel Cell Power
      Plant.
AB  - This paper describes a mathematical model of a solid oxide fuel cell (SOFC) power
      plant integrated in a multimachine power system. The utilization factor of a fuel
      stack maintains steady state by tuning the fuel valve in the fuel processor at a
      rate proportional to a current drawn from the fuel stack. A suitable fuzzy logic
      control is used for the overall system, its objective being controlling the
      current drawn by the power conditioning unit and meet a desirable output power
      demand. The proposed control scheme is verified through computer simulations.

PMID- 25053927
TI  - Farewell to prof. Dr. Dr. Walter sibrowski.

PMID- 25053928
TI  - Hemovigilance.

PMID- 25053929
TI  - Role of Riboflavin- and UV Light-Treated Plasma in Prevention of Transfusion
      Related Acute Lung Injury.
AB  - INTRODUCTION: Risk reduction strategies for transfusion-related acute lung injury
      (TRALI) include the preferential use of male donors to provide fresh frozen
      plasma (FFP). Implementing this measure based on FFP quarantine program is a very
      complex process. To improve FFP inventory management and the availability of FFP
      from male donors, the Mirasol Pathogen Reduction Technology((r)) (PRT) system for
      FFP using riboflavin and UV light was adopted in our region in 2012. METHODS: The
      percentage of male/female FFP units issued and TRALI cases in patients receiving
      FFP in the period before implementing riboflavin and UV light (2010-2011) was
      compared with the period post implementation of riboflavin and UV light (2012
      2013). RESULTS: In 2010 and 2011, there was one FFP transfusion-related TRALI
      case reported per year, when the proportion of male/female FFP distributed to the
      hospitals was 60/40. During 2012 and 2013, there have been no FFP transfusion
      related TRALI cases, when the proportion of male/female FFP distributed to the
      hospitals was around 97/3. Mirasol PRT allows quick availability (24 h from
      collection) compared to quarantined FFP (>=3 months from collection). CONCLUSION:
      Thanks to its readiness, simplicity and feasibility, riboflavin- and UV light
      treated FFP implementation can facilitate the preferential use of FFP from male
      donors as a TRALI prevention strategy.

PMID- 25053930
TI  - Transfusion efficacy of apheresis platelet concentrates irradiated at the day of
      transfusion is significantly superior compared to platelets irradiated in
      advance.
AB  - BACKGROUND: Gamma irradiation is currently the standard care to avoid transfusion
      associated graft-versus-host disease. Guidelines on gamma irradiation of blood
      components state that platelets (PLTs) can be irradiated at any stage in their 5
      day storage and can thereafter be stored up to their normal shelf life of 5 days
      after collection. In this study, we explored whether the timing of irradiation
      has an effect on transfusion efficacy of apheresis PLT concentrates (APCs).
      METHODS: Based on the 1-hour percent PLT recovery (PPR1h), transfusion efficacy
      of 1,000 eligible APCs transfused to 144 children were evaluated retrospectively.
      PPR1h was compared in transfused APCs irradiated at the day of transfusion and
      APCs irradiated in advance. RESULTS: In univariate analysis, transfusion efficacy
      of APCs irradiated in advance was significantly lower than that of APCs
      irradiated at the day of transfusion (mean PPR1h 27.7 vs. 35.0%; p = 0.007). This
      was confirmed in multivariate analysis (p = 0.030). Compared to non-irradiated
      APCs, transfusion efficacy of APCs irradiated at the day of transfusion was not
      significantly inferior (mean difference -2.8%; 95% CI -6.1 to 0.5%; p = 0.092),
      but APCs irradiated in advance were clearly less efficient (mean difference 
      8.1%; 95% CI -12.2 to -4.0%; p < 0.001). CONCLUSION: Our data strongly support
      that APCs should not be irradiated in advance, 1.e., >=24 h before transfusion.

PMID- 25053931
TI  - A Simple Guideline Reduces the Need for Red Blood Cell Transfusions in Swiss
      Hospitals: A Prospective, Multicentre, Before-and-After Study in Elective Hip and
      Knee Replacement.
AB  - INTRODUCTION: Optimising the use of blood has become a core task of transfusion
      medicine. Because no general guidelines are available in Switzerland, we analysed
      the effects of the introduction of a guideline on red blood cell (RBC)
      transfusion for elective orthopaedic surgery. METHODS: Prospective, multicentre,
      before-and-after study comparing the use of RBCs in adult elective hip or knee
      replacement before and after the implementation of a guideline in 10 Swiss
      hospitals, developed together with all participants. RESULTS: We included 2,134
      patients, 1,238 in 7 months before, 896 in 6 months after intervention. 57 (34 or
      2.7% before, 23 or 2.6% after) were lost before follow-up visit. The mean number
      of transfused RBC units decreased from 0.5 to 0.4 per patient (0.1, 95% CI 0.08
      0.2; p = 0.014), the proportion of transfused patients from 20.9% to 16.9% (4%,
      95% C.I. 0.7-7.4%; p = 0.02), and the pre-transfusion haemoglobin from 82.6 to
      78.2 g/l (4.4 g/l, 95% C. I. 2.15-6.62 g/l, p < 0.001). We did not observe any
      statistically significant changes in in-hospital mortality (0.4% vs. 0%) and
      morbidity (4.1% vs. 4.0%), median hospital length of stay (9 vs. 9 days), follow
      up mortality (0.4% vs. 0.2%) and follow-up morbidity (6.9% vs. 6.0%).
      CONCLUSIONS: The introduction of a simple transfusion guideline reduces and
      standardises the use of RBCs by decreasing the haemoglobin transfusion trigger,
      without negative effects on the patient outcome. Local support, training, and
      monitoring of the effects are requirements for programmes optimising the use of
      blood.

PMID- 25053932
TI  - Hemostatic function and transfusion efficacy of apheresis platelet concentrates
      treated with gamma irradiation in use for thrombocytopenic patients.
AB  - BACKGROUND: During the transfusion of blood components, the transfer of
      allogeneic donor white blood cells (WBCs) can mediate transfusion-associated
      graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood
      products to gamma irradiation is currently the standard of care. The aim of our
      study was to evaluate and compare hemostatic function, transfusion efficacy, and
      safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and
      of conventional non-irradiated PCs in patients with chemotherapy-induced
      thrombocytopenia. METHODS: 20 double-dose single-donor leukoreduced PCs were
      split in two identical units; one was gamma-irradiated with 25 Gy (study arm A)
      and the other remains non-irradiated (study arm B). Both units were stored under
      equal conditions. Hematologic patients were randomly assigned to receive gamma
      irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated
      by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1
      and 24 h post transfusion. TEG profiles were measured, noting the time to
      initiate clotting (R), the angle of clot formation (alpha), and the maximum
      amplitude (clot strength (MA)). Whole blood samples were collected from these
      thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and
      corrected count increments (CCIs) with assessments of transfusion efficacy. Time
      to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and
      adverse events (AEs), were analyzed. RESULTS: No differences could be found in
      hemostatic function parameters (MA, R, and alpha) between study arms A and B (all
      p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No
      differences between study arms A and B were observed for mean (+/- standard
      deviation (SD)) 1-hour CCI (12.83 +/- 6.33 vs. 11.59 +/- 5.97) and 24-hour CCI
      (6.56 +/- 4.10 vs. 5.76 +/- 4.05). Mean 1-hour CI and 24-hour CI were not
      significantly different in both study arms (p = 0.254 and p = 0.242
      respectively). Median time to the next PC transfusion after study PC was not
      significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No
      differences could be found in transfusion requirement of red blood cells (p =
      0.744) between both study arms. There were also no regarding bleeding, adverse
      events, and acute transfusion reaction(s). CONCLUSIONS: This study confirms
      safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic
      function, transfusion efficacy, bleeding, and safety of single-donor apheresis
      PCs treated with gamma irradiation versus untreated control PCs are comparable.

PMID- 25053933
TI  - Storage-induced damage to red blood cell mechanical properties can be only
      partially reversed by rejuvenation.
AB  - BACKGROUND: The storage of red blood cells (RBC) is associated with impairment of
      their properties that can induce a circulatory risk to recipients. In a preceding
      study (2009), we reported that post-storage rejuvenation (RJ) of stored RBC (St
      RBC) efficiently reduced the storage-induced RBC/endothelial cell interaction,
      while only partially reversing the level of intracellular Ca(2+), reactive oxygen
      species, and surface phosphatidylserine. In the present study, we examined the RJ
      effectiveness in repairing St-RBC mechanical properties. METHODS: RBC, stored in
      CPDA-1 without pre-storage leukoreduction, were subjected to post-storage RJ, and
      the deformability, osmotic fragility (OF), and mechanical fragility (MF) of the
      rejuvenated St-RBC (St-RBCRj) were compared to those of untreated St-RBC and of
      freshly-collected RBC (F-RBC). RESULTS: 5-week storage considerably increased OF
      and MF, and reduced the deformability of St-RBC. All alterations were only
      partially (40-70%) reversed by RJ, depending on the extent of the damage: the
      greater the damage, the lesser the relative effect of RJ. CONCLUSION: The
      findings of the present and preceding studies suggest that different St-RBC
      properties are differentially reversed by RJ, implying that some of the changes
      occur during storage and are irreversible.

PMID- 25053934
TI  - Development, manufacturing and characterization of a highly purified, liquid
      immunoglobulin g preparation from human plasma.
AB  - BACKGROUND: The use of plasma-derived immunoglobulin G (IgG) is increasing, and
      the number of diseases, including immunodeficiencies, neurological diseases and
      autoimmune conditions, treated with intravenous IgG (IVIG) is expanding.
      Consequently, there is a great need for high-yield production processes for
      plasma-derived IgG. The aim of this work was to develop a high-yield process
      leading to a highly purified, liquid, ready-to-use IgG for intravenous use.
      METHODS: Plasma from healthy, voluntary, non-remunerated donors was fractionated
      by ethanol precipitation. IgG was extracted from fraction II + III using a
      phosphate/acetate buffer, pH 4, and purified by chromatography. RESULTS:
      Precipitation with 6% polyethylene glycol at pH 7 removed high molecular-weight
      contaminating proteins, aggregates and contaminating viruses. Ion exchange
      chromatography at pH 5.7 on serially connected anion and cation exchange columns
      allowed for elution of IgG from the cation exchange column in good yield and high
      purity. Further safety was achieved by solvent/detergent treatment and repeated
      ion exchange chromatography. The product consisted of essentially only IgG
      monomers and dimers, and had a high purity with very low levels of IgM and IgA.
      CONCLUSION: A process providing highly purified IVIG in good yield was developed.

PMID- 25053936
TI  - Assessment of Impact of Training in Improving Knowledge of Blood Transfusion
      among Clinicians.
AB  - BACKGROUND: Blood is a precious resource that needs to be prescribed, handled,
      stored and transfused as per guidelines to ensure recipient safety. The present
      study aims to assess the basic knowledge of clinicians pertaining to safe
      transfusion practice, impart relevant training, and assess the impact of such
      training programs. METHODS: A total of 25 fresh bachelor of medicine and bachelor
      of surgery graduates were enrolled for the study. The participants were given a
      pre-assessment questionnaire related to the entire transfusion chain followed by
      interactive training of the participants and post-training re-assessment.
      RESULTS: The mean score in the pre-training assessment was 51% while in the post
      training assessment the mean score was 85.4%; the difference was statistically
      significant. There were significant differences in knowledge pertaining to
      storage temperature, shelf life of red cells and platelets, alternate group
      choice for fresh frozen plasma, and documentation of transfusion reaction. The
      participants had inadequate knowledge pertaining to cross-match procedure and
      management of transfusion reactions. CONCLUSION: The study assessed the knowledge
      and awareness of clinicians regarding blood transfusion practice. Mandatory
      training and inclusion of transfusion medicine as a subject at undergraduate
      level can help in improving transfusion practice and ensuring recipient safety.

PMID- 25053937
TI  - Visual context due to speech-reading suppresses the auditory response to acoustic
      interruptions in speech.
AB  - Speech reading enhances auditory perception in noise. One means by which this
      perceptual facilitation comes about is through information from visual networks
      reinforcing the encoding of the congruent speech signal by ignoring interfering
      acoustic signals. We tested this hypothesis neurophysiologically by acquiring EEG
      while individuals listened to words with a fixed portion of each word replaced by
      white noise. Congruent (meaningful) or incongruent (reversed frames) mouth
      movements accompanied the words. Individuals judged whether they heard the words
      as continuous (illusion) or interrupted (illusion failure) through the noise. We
      hypothesized that congruent, as opposed to incongruent, mouth movements should
      further enhance illusory perception by suppressing the auditory cortex's response
      to interruption onsets and offsets. Indeed, we found that the N1 auditory evoked
      potential (AEP) to noise onsets and offsets was reduced when individuals
      experienced the illusion during congruent, but not incongruent, audiovisual
      streams. This N1 inhibitory effect was most prominent at noise offsets,
      suggesting that visual influences on auditory perception are instigated to a
      greater extent during noisy periods. These findings suggest that visual context
      due to speech-reading disengages (inhibits) neural processes associated with
      interfering sounds (e.g., noisy interruptions) during speech perception. 

PMID- 25053938
TI  - High-intensity focused ultrasound treatment for advanced pancreatic cancer.
AB  - Pancreatic cancer is under high mortality but has few effective treatment
      modalities. High-intensity focused ultrasound (HIFU) is becoming an emerging
      approach of noninvasively ablating solid tumor in clinics. A variety of solid
      tumors have been tried on thousands of patients in the last fifteen years with
      great success. The principle, mechanism, and clinical outcome of HIFU were
      introduced first. All 3022 clinical cases of HIFU treatment for the advanced
      pancreatic cancer alone or in combination with chemotherapy or radiotherapy in
      241 published papers were reviewed and summarized for its efficacy, pain relief,
      clinical benefit rate, survival, Karnofsky performance scale (KPS) score, changes
      in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of
      outcome, and associated complications. Immune response induced by HIFU ablation
      may become an effective way of cancer treatment. Comments for a better outcome
      and current challenges of HIFU technology are also covered. 

PMID- 25053935
TI  - Physiology of iron metabolism.
AB  - A revolution occurred during the last decade in the comprehension of the
      physiology as well as in the physiopathology of iron metabolism. The purpose of
      this review is to summarize the recent knowledge that has accumulated, allowing a
      better comprehension of the mechanisms implicated in iron homeostasis. Iron
      metabolism is very fine tuned. The free molecule is very toxic; therefore,
      complex regulatory mechanisms have been developed in mammalian to insure adequate
      intestinal absorption, transportation, utilization, and elimination. 'Ironomics'
      certainly will be the future of the understanding of genes as well as of the
      protein-protein interactions involved in iron metabolism. 

PMID- 25053939
TI  - A gastrointestinal electrical stimulation system based on transcutaneous power
      transmission technology.
AB  - Electrical stimulation has been suggested as a possible treatment for various
      functional gastrointestinal disorders (FGID). This paper presents a
      transcutaneous power supplied implantable electrical stimulation system. This
      technology solves the problem of supplying extended power to an implanted
      electrical stimulator. After implantation, the stimulation parameters can be
      reprogrammed by the external controller and then transmitted to the implanted
      stimulator. This would enable parametric studies to investigate the efficacy of
      various stimulation parameters in promoting gastrointestinal contractions. A
      pressure detector in the internal stimulator can provide real-time feedback about
      variations in the gastrointestinal tract. An optimal stimulation protocol leading
      to cecal contractions has been proposed: stimulation bursts of 3 ms pulse width,
      10 V amplitude, 40 Hz frequency, and 20 s duration. The animal experiment
      demonstrated the functionality of the system and validated the effects of
      different stimulation parameters on cecal contractions. 

PMID- 25053940
TI  - Imaging in gastroenterology.

PMID- 25053941
TI  - HIV Risk Perception, Sexual Behavior, and HIV Prevalence among Men-Who-Have-Sex
      with-Men at a Community-Based Voluntary Counseling and Testing Center in Kuala
      Lumpur, Malaysia.
AB  - We describe the HIV risk perception, sexual behavior, and HIV prevalence among
      423 men-who-have-sex-with-men (MSM) clients who received voluntary counseling and
      testing (VCT) services at a community-based center in Kuala Lumpur, Malaysia. The
      mean age was 29 years old. One hundred one (23.9%) clients rated themselves as
      low risk, 118 (27.9%) as medium risk, 36 (8.5%) as high risk, and 168 (39.7%)
      were unsure of their risk. Twenty-four (9.4%) clients tested HIV positive (4 (4%)
      low risk, 9 (7.6%) medium risk, 11 (30.6%) high risk, and 13 (7.7%) unsure risk).
      We found a positive correlation between risk perception and HIV infection in this
      study. Clients with high HIV risk perception have 17x the odds of testing HIV
      positive compared to low risk clients. High HIV risk perception was significantly
      associated with multiple sex partners, multiple types of sex partners, alcohol
      use before intercourse, unprotected sex beyond 6 months, and inconsistent condom
      use during anal sex compared to low risk clients. There were no statistically
      significant differences between medium risk and unsure risk clients compared to
      low risk clients. Strategies should be targeted towards change in sexual
      practices among those who are perceived to be at high risk. 

PMID- 25053942
TI  - Prevalence of amiodarone-induced thyrotoxicosis and associated risk factors in
      Japanese patients.
AB  - Amiodarone is a widely used agent for life-threatening arrhythmias. Although
      amiodarone-induced thyrotoxicosis (AIT) is a major adverse effect that can cause
      recurrence of arrhythmias and exacerbation of heart failure, risk factors for AIT
      among amiodarone-treated Japanese patients have not been elucidated. Here, we
      investigated the prevalence and predictive factors for AIT. The study subjects
      were 225 patients treated with amiodarone between 2008 and 2012, who were
      euthyroid before amiodarone therapy. All patients with AIT were diagnosed by
      measurement of thyroid hormones and ultrasonography. Among the 225 subjects, 13
      patients (5.8%) developed AIT and all the patients were classified as Type 2 AIT.
      Baseline features of patients with AIT were not different from those who did not
      develop AIT, except for age (AIT, 55.1 +/- 13.8, non-AIT, 68.1 +/- 12.0 years, P
      < 0.001). Multivariate analyses using the Cox proportional hazard model
      identified age as the sole determinant of AIT (hazard ratio: 0.927, 95%
      confidence interval: 0.891-0.964). Receiver operating characteristic curve
      analysis identified age of 63.5 years as the cutoff value for AIT with
      sensitivity of 70.3% and specificity of 69.2%. In summary, this study showed that
      the prevalence of AIT is 5.8% in Japanese patients treated with amiodarone and
      that young age is a risk factor for AIT. 

PMID- 25053943
TI  - Vitamin d binding protein and vitamin d levels.

PMID- 25053944
TI  - The effect of renal dysfunction on circulating sclerostin level in patients with
      type 2 diabetes.
AB  - Objective. Sclerostin is a Wnt inhibitor produced specifically by osteocytes.
      However, it is not currently clear whether renal dysfunction has an effect on
      circulating sclerostin level in patients with type 2 diabetes. The aim of the
      study was to evaluate this relationship. Design and Patients. We conducted a
      cross-sectional observational study of 302 type 2 diabetic patients with or
      without chronic kidney disease. Serum sclerostin level was analyzed by ELISA, and
      renal function was assessed by estimated glomerular filtration rate (eGFR) using
      chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Results.
      There was a strong correlation between sclerostin level with renal function
      presented as serum creatinine (r = 0.745, P < 0.001) and eGFR (r = -0.590, P <
      0.001). Serum sclerostin level was significantly higher in patients with CKD-G3
      stage than those with CKD-G1/2 stages after adjusting for age, sex, and BMI (P =
      0.011). Patients with CKD-G4/5 stages had dramatically increased level of
      circulating sclerostin. Multiple regression analyses found that age, sex, and
      eGFR were independent determining factors for circulating sclerostin level.
      Conclusion. Our data showed that serum sclerostin levels start to increase in
      diabetic patients with CKD-G3 stage. Further studies are needed to establish the
      potential role of elevated sclerostin in diabetic patients with CKD. 

PMID- 25053946
TI  - Common periodontal diseases of children and adolescents.
AB  - Background. Since 2000, studies, experiments, and clinical observations revealed
      high prevalence of periodontal diseases among children and adolescents.
      Therefore, this paper was designed to provide an update for dental practitioners
      on epidemiology, microbiology, pathology, prevention, diagnosis, and treatment of
      periodontal diseases in children and adolescents. Methods. This paper reviews the
      current literature concerning periodontal diseases in pediatric dentistry. It
      includes MEDLINE database search using key terms: "periodontal diseases in
      children," "Periodontal diseasesin adolescents," "periodontal diseases risk
      factors," "microbiology of periodontal diseases," "classification of periodontal
      diseases," "epidemiology of periodontal diseases," and "treatment of periodontal
      diseases." Articles were evaluated by title and/or abstract and relevance to
      pediatric dentistry. Sixty-five citations were selected by this method and by the
      references within the chosen articles. A review of the comprehensive textbooks on
      pediatric dentistry and periodontology was done. Some recommendations were based
      on the opinions of experienced researchers and clinicians, when data were
      inconclusive. 

PMID- 25053948
TI  - Microbiologic Spectrum and Antibiotic Susceptibility Pattern among Patients with
      Urinary and Respiratory Tract Infection.
AB  - Aim. To demonstrate the prevalence of isolated organisms in urinary/respiratory
      tract infections and their antibiotic susceptibilities in a tertiary care center.
      Methods and Material. Between January 2008 and January 2010, patients referring
      to the clinic of cardiology or those admitted to the cardiac wards were enrolled
      in this cross-sectional descriptive study. Urine and sputum sampling was done for
      all the patients and the specimens underwent microbiologic examination and, in
      case of isolation of microorganism, antibiotic disk diffusion test was performed.
      Results. Escherichia coli (E. coli) was the most prevalent isolated organism in
      hospital and community-acquired UTIs and was highly resistant to cephalothin in
      all the samples followed by cotrimoxazole, and ceftriaxone. It revealed high
      sensitivity to imipenem, amikacin, and nitrofurantoin. Acinetobacter constituted
      the most prevalent organism isolated from respiratory secretions and represented
      the highest resistance to ceftriaxone and the greatest sensitivity to imipenem.
      Conclusions. E. coli and Acinetobacter remain the most common uropathogenic and
      respiratory organisms, respectively. However, their increasing resistance to wide
      spectrum imipenem, meropenem, and vancomycin is a major concern. 

PMID- 25053947
TI  - Synthesis, Characterization, and Osteoblastic Cell Culture of Poly(L-co-D,L
      lactide-co-trimethylene carbonate) Scaffolds.
AB  - Lactide-based polymers have been widely investigated as materials for tissue
      engineering. However, characteristics such as low flexibility and elongation tend
      to limit particular applications, although these can be enhanced by adding
      plasticizers such as trimethylene carbonate (TMC) to the polymer chain of the
      copolymer poly(L-lactide-co-D,L-lactide) (PLDLA). The aim of this work was to
      synthesize and characterize a terpolymer of L-lactide, D,L-lactide, and TMC. The
      polymers were synthesized from 30% TMC by bulk polymerization and resulted in an
      average molar mass >10(5) g/mol. Thermal investigation of PLDLA-TMC showed a
      decrease in the glass transition and onset temperatures compared to PLDLA. PLDLA
      TMC scaffolds stimulated the proliferation and normal phenotypic manifestations
      of cultured osteoblasts. These results show that it was possible to produce a
      terpolymer from L-lactide, D,L-lactide, and TMC. Scaffolds of this terpolymer had
      important characteristics that could be useful for applications in bone tissue
      engineering. 

PMID- 25053949
TI  - Regional pericarditis or an alternate diagnosis?

PMID- 25053950
TI  - Superior mesenteric artery syndrome in a patient with cerebral palsy.
AB  - Superior mesenteric artery syndrome involves compression of the third part of the
      duodenum due to narrowing of the area between the aorta and the superior
      mesenteric artery (SMA). We will describe the case of a 34-year-old with cerebral
      palsy who presented with abdominal pain, nausea, vomiting, and weight loss and
      was diagnosed with SMA syndrome via CT-imaging. With failure of conservative
      measures, our patient underwent a duodenojejunostomy after which improvement in
      her weight as well as relief of her abdominal symptoms was noted. Given the
      rarity of this syndrome, physicians need to keep a high index of suspicion in
      order to prevent the damaging consequences. 

PMID- 25053951
TI  - Prevention of physicians' suicide.
AB  - Suicide rate in physicians has been reported to be higher than general population
      or other academics. Previous studies found that 85-90% of people who commit
      suicide had been suffering from some type of psychiatric disorder. Suicide
      prevention is the key element in lowering the numbers of physicians who destroy
      themselves and end their lives each year. It is needed to provide some
      educational programs to increase physicians' awareness of warning signs of
      suicidal ideation such as observable signs of serious depression. According to
      previous studies, some specialties such as psychiatry, anesthesiology, and
      dentistry are at higher risk for physicians' suicide. Hence, it is important to
      select candidates in these fields carefully as a primary prevention program. 

PMID- 25053952
TI  - The efficacy of group metacognitive therapy on self-esteem and mental health of
      patients suffering from major depressive disorder.
AB  - OBJECTIVE: The present research aims to analyze the efficacy of group
      metacognitive therapy (MCT) on self-esteem and mental Health of those who suffer
      from major depressive disorder. METHODS: The research was a randomized clinical
      controlled trial, using pretest and posttest with 2 months of follow-up. Twenty
      two patients with major depressive disorder based on DSM-IV-TR criteria were
      selected through available sampling from patients of two psychiatric hospitals of
      Mashhad, Iran, in 2011. They were allocated randomly into two groups of trial (n
      = 11) and control (n = 11). Citalopram and sertraline were prescribed as
      antidepressant to both groups. The experimental group also attended nine 90
      minute sessions of MCT (a 5-week program). Eysenck self-esteem scale (ESES) and
      Mental Health Checklist (MHC) were used in pretest, posttest, and follow-up as
      the study instrument. The data were analyzed by analysis of covariance (ANCOVA)
      using SPSS. RESULTS: ANCOVA revealed that the patients receiving group MCT had
      significantly increased (p < 0.001) self-esteem in posttest, which remained
      significant in the follow up (p < 0.001). Moreover, mental health scores had
      increased in the MCT group (posttest, p < 0.001; follow up, p < 0.001).
      CONCLUSION: Group MCT has beneficial therapeutic roles in improving the self
      steam and recuperation of mental health in MDD patients.

PMID- 25053954
TI  - Evaluating the cognition, behavior, and social profile of an adolescent with
      learning disabilities and assessing the effectiveness of an individualized
      educational program.
AB  - OBJECTIVE: The present study seeks to outline a holistic assessment method that
      was used in understanding problems experienced by an adolescent boy and in
      designing and implementing an individualized educational program. METHODS: An
      adolescent child referred for concerns in learning was screened for learning
      disability using standardized inventories and test batteries. The Connors Parent
      and Teacher Rating Scales (short forms), Wechsler's Intelligence Scale for
      Children (WISC), the Vineland Social Maturity Scale (VSMS), and the Kinetic
      Family Drawing (KFD) test were used to assess the behavior, cognition, and social
      profile of the child. An individualized educational program was designed and this
      intervention was provided for 6 months by using parents as co-therapists.
      Participant and parent interview schedules were used in identifying underlying
      issues of concern. The child was reassessed 6 months after the intervention was
      provided. RESULTS: Findings on the Connors Parent Rating Scale revealed scores
      that were greater than the 50(th) percentile on the domains of inattention and
      cognitive problems. On the Connors Teacher Rating Scale, we observed scores
      greater than the 50(th) percentile on the hyperactivity, cognitive problems, and
      the inattention domains. The WISC revealed that the child had a "Dull Normal"
      Intellectual functioning and there was also a deficit of 2 years on the social
      skills as tested by the Vineland Social Maturity Scale (VSMS). The Kinetic Family
      Drawing Test revealed negative emotions within the child. Post intervention, we
      noticed a remarkable improvement in the scores across all domains of behavior,
      social, and cognitive functioning. CONCLUSION: Designing an individualized
      education program that is tailored to the specific needs of the child and using
      parents as co-therapists proved to be an effective intervention.

PMID- 25053953
TI  - Bio-psycho-socio-demographic and Obstetric Predictors of Postpartum Depression in
      Pregnancy: A prospective Cohort Study.
AB  - OBJECTIVE: There are various attempts to confirm variables that could predict
      postpartum depression in advance. This study determined antenatal risk factors
      for postpartum depression in women at risk of developing this disorder. METHODS:
      A prospective cohort study was conducted with 2279 eligible women who attended at
      Mazandaran province' primary health centers from 32-42 weeks of pregnancy to
      eighth postpartum weeks. The women were screened for symptoms of depression using
      the Iranian version of Edinburgh Postnatal Depression Scale. An Edinburgh
      Postnatal Depression Scale score of > 12 indicated possible postpartum
      depression. Univariate and multiple logistic regression models were used for data
      analysis. RESULTS: A total of 2083women during 32-42 weeks of gestation
      participated in this study and were followed up to 8-week postpartum. Four
      hundred and three (19.4%) mothers yielded scores above the threshold of 12.
      Depression and general health state in pregnancy based on Edinburgh Postnatal
      Depression Scale (OR = 1.35, CI = 1.3-1.4) and General Health Questionnaire-28
      (OR = 1.03, CI = 1.01-1.04), respectively were significant independent antenatal
      risk factors of depression symptoms at 8-week postpartum. Mothers who lived in
      nuclear families (OR = 1.38, CI = 1.04-1.84), whose husbands had lower
      educational status (OR = 0.95, CI = 0.91-0.99), and with delayed prenatal care
      (OR = 1.01, CI = 1.001-1.03) were more susceptible to postpartum depression.
      CONCLUSION: A comprehensive antenatal assessment focused on psychiatric problems,
      environmental and obstetric factors would benefit pregnant women in the
      prevention of postpartum depression.

PMID- 25053955
TI  - Study of attitudes and practice of physicians regarding consultation-liaison
      psychiatry in teaching hospitals of mazandaran, iran.
AB  - OBJECTIVE: Consultation-liaison (CL) psychiatry interfaces between psychiatry and
      other medical disciplines to promote integrated care of patients. The purpose of
      this study is evaluation of attitudes and practice of Mazandaran University of
      Medical Sciences physicians of teaching hospitals regarding CL psychiatry.
      METHODS: In this descriptive study, all of the general practitioners, specialist
      and subspecialist physicians and assistants working in teaching hospitals of
      Mazandaran University of Medical Sciences were requested to fill in a
      questionnaire which was designed based on previous studies and observations to
      assess their attitudes and practice. Data were analysed by SPSS-16 software,
      using chi square. RESULTS: One hundred and forty nine (62.6%) physicians had very
      positive attitudes and 89 cases (37.4%) had positive attitudes; 234 physicians
      (98.3%) had acceptable practice, and 4 cases (1.7%) had unacceptable practice.
      There were no significant differences between physicians with positive and very
      positive attitudes and between physicians with acceptable and unacceptable
      practice regarding gender, age, education, specialty and place of work
      (hospital). The most common reasons of physicians for not requesting psychiatric
      consultation were lack of time, forgetfulness, lack of access to psychiatrist,
      and lack of belief in the need for psychiatric consultation respectively.
      CONCLUSION: The findings of this study indicate the successful psychiatric
      educations and psychiatrists practice in formation of positive attitudes and
      acceptable practice regarding CL Psychiatry in these university hospitals. No
      significant differences between different specialties and work place hospitals
      indicate that they are similarly affected.

PMID- 25053956
TI  - The Relationship between Marital and Sexual Satisfaction among Married Women
      Employees at Golestan University of Medical Sciences, Iran.
AB  - OBJECTIVE: There are various elements affecting the healthy family such as
      marital satisfaction. Various factors such as sexual satisfaction have an
      important impact on satisfaction of marital relationship. The present study aimed
      to determine the association of marital satisfaction with sexual satisfaction
      among sexually active employee women. METHODS: This analytical descriptive study
      was carried on 140 married women employed at educational and medical centers of
      Golestan University of Medical Sciences. Questionnaires for data collection
      included Enrich Marital Satisfaction Questionnaire and self-constructed
      questionnaire (demographic characteristic and sexual satisfaction). Data were
      analyzed using descriptive statistics, chi(2) and Spearman statistical test.
      Statistical significant level was set as 0.05. RESULTS: The findings showed that
      in marital satisfaction scale, the majority of the participants (63.6%) were very
      satisfied and none of them were very unsatisfied. In sexual satisfaction scale,
      most of the participants (56.4%) expressed extremely satisfaction rate and only
      0.7% were not satisfied with their sexual relationship. Marital satisfaction was
      significantly associated with sexual satisfaction (p <= 0.001). So with the
      increase of sexual satisfaction, there was an increase in marital satisfaction
      accordingly. The findings indicated that there was a significant association
      between sexual satisfaction and age (p = 0.086). Level of education was
      associated significantly with the marital satisfaction (p = 0.038). The effects
      of sexual satisfaction on marital satisfaction were moderated by number of
      children and the level of education. CONCLUSION: The findings have implications
      for improving of couples' marital satisfaction by highlighting the need for
      awareness of sexual quality. According to the findings, it seems that development
      of educational programs and pre-marriage counseling is necessary. Continuous
      education would be helpful after marriage in addressing couples' unique
      transitional needs in marital life.

PMID- 25053957
TI  - Protective Factors Enhancing Prosocial Behavior and Preventing Internalizing and
      Externalizing Symptoms among Adolescents Living in Forster Care Homes.
AB  - OBJECTIVE: Based on Problem Based Theory, this study investigated a broad array
      of putative protective factors associated with psychopathological symptoms and
      prosodical behaviour. METHODS: Participants were 140 orphan adolescent girls and
      boys living in foster care homes in Tehran, chosen with convenience sampling
      procedures. Using a cross-sectional design this study examined the individual and
      interactive properties of protective factors in this high-risk population.
      RESULTS: Findings with theoretically derived multi-item subscales indicated a
      high degree of association specificity based on type of psychopathology and
      depending on gender. RESULTS with the whole sample indicated that theoretically
      derived individual protective factor scales associations were obtained mainly for
      conduct problems and emotional symptoms, and with girls only. CONCLUSION: The
      present study provides introductory information on the identification of
      protective factors that can be utilized in educational, interventional and
      preventive public health programs for this high-risk population. One innovative
      contribution of the present research is to provide an introductory validation of
      a theory-based model of adolescent protection and resilience, for which there is
      ample empirical support, in a high-risk population of Iranian adolescents living
      in foster homes centers in a metropolitan urban setting.

PMID- 25053958
TI  - Efficacy of life skills training on subjective well-being of students: a report
      from rafsanjan, iran.
AB  - OBJECTIVE: The aim was to investigate the efficacy of life skills training on
      subjective well-being (SWB) among high school females. METHODS: The population
      study comprised all female high school of Rafsanjan, Iran, in 2008-2009. Thirty
      students with the lowest scores according to the Molavi's SWB questionnaire were
      considered eligible. At the next stage, the required sample of 30 students were
      selected randomly and divided into two groups of experimental (15 subjects) and
      control (15 subjects). Then, life skills training sessions were started for the
      experimental group (eight sessions in a 4-week period). Control group did not
      receive any intervention. The method of data processing at a descriptive level
      was through using central tendency indicators, dispersion, frequency, and
      percentage. Student's t-test was used for analysis of independent variables.
      RESULTS: The greatest R(2) (0.48) was observed for SWB. The R(2) coefficients for
      neurosis, stress-depression, vitality, and life determination were 0.27, 0.15,
      0.20, and 0.09, respectively. CONCLUSION: Life skills training showed the
      greatest effect regarding SWB of the students.

PMID- 25053959
TI  - Comparison of Behavioral and Sexual Problems between Intellectually Disabled and
      Normal Adolescent Boys during Puberty in Yazd, Iran.
AB  - OBJECTIVE: To compare sexual and behavioral puberty problems between
      intellectually disabled (ID) and normal boys in Yazd, Iran. METHODS: In the
      present study, 65 intellectually disabled and 65 normal boys were included. The
      Child Behavior Check List (CBCL) was used to investigate behavioral problems. In
      order to study sexual problems, a questionnaire that was designed by the
      researchers was applie. RESULTS: Anxiety, depression, social problems, attention
      problems, aggressiveness, and sexual problems were more frequent in
      intellectually disabled boys than in normal boys. On the other hand, regarding
      somatic complaints, withdrawal, thought problems, internalizing, delinquent
      behavior, and externalizing there was no difference between the two groups.
      CONCLUSION: Behavioral and sexual problems are more common in adolescent boys
      with intellectual disability (ID) than in normal boys during the puberty period.
      Therefore, puberty is an important period for intellectually disabled boys and
      their families; this should be taken into consideration by psychologists and
      clinicians.

PMID- 25053960
TI  - Prevalence of Addiction to the Internet, Computer Games, DVD, and Video and Its
      Relationship to Anxiety and Depression in a Sample of Iranian High School
      Students.
AB  - OBJECTIVE: The objective of this study was to assess the prevalence of addiction
      to the Internet, computer games, DVD, and video and its relationship to anxiety
      and depression in a sample of Iranian high school students. METHODS: In this
      cross-sectional study 1020 high school students (males and females) were selected
      randomly from different areas of Shiraz city in southern Iran. They were
      interviewed according to the Diagnostic and Statistical Manual of Mental
      Disorders, 4(th) ed (DSM-IV) criteria. RESULTS: About 50% of the students were
      females, 277 students (27.2%) were studying in the first year of high school, 242
      (23.7%) were in the second year, and others in the third year. The prevalence of
      anxiety was significantly higher in females than in males (p < 0.05). The
      prevalence of anxiety was lower among students of the third year (p < 0.05). The
      prevalence of depression was significantly higher in students with lower economic
      status defined as family monthly income. Internet dependence was seen only in 5
      students. The prevalence of anxiety was significantly higher in the students who
      used internet for chatting, amusement, and reading news (p < 0.05). The
      prevalence of anxiety was significantly higher in students who were DVD or video
      CD dependents (p < 0.05). The students who used especial drugs or had especial
      diseases had higher rates of depression and anxiety (p < 0.05). CONCLUSION:
      Internet addiction may cause depression and anxiety in high school students. It
      seems necessary to develop an Internet addiction prevention program for
      adolescents taking into account the psychological factors such as depression and
      Internet use habits.

PMID- 25053961
TI  - Drug Abuse among University Students of Rafsanjan, Iran.
AB  - OBJECTIVE: The present study aimed to determine the frequency of drug abused in a
      sample of university students in Rafsanjan, Iran. METHODS: In this cross
      sectional study, 1,260 students volunteered (311 males and 949 females) with mean
      age of 21.35 years. Data were collected by a self-administrated questionnaire
      regarding drugs abuse and demographic information. RESULTS: Benzodiazepines were
      the most common abused drugs which were reported in 94 students (7.4%). Other
      agents studied were cigarette and tobacco (159, cases 12.6%), alcoholic drinks
      (60 cases, 4.7%), and opiates (42 cases, 3.3%). Forty-three students (3.4%) had
      used methylphenidate in the last 6 months. Of this, 39 (90.6%) experienced
      insomnia. All students who abused methylphenidate indicated that the reason for
      this behavior was to raise alertness and conscious levels. CONCLUSION: The
      pattern of drug abuse among the students here seems similar to other reports from
      Iranian universities.

PMID- 25053962
TI  - Familial characteristics of street children in tehran, iran.
AB  - OBJECTIVE: The phenomenon of street children is one of the most important
      concerns facing global community. Identifying risk factors in such children could
      lead to crucial investigations to find their essential needs by intervention
      programs. The present study examined the family profile of street children in
      Tehran, Iran. METHODS: The sample consisted of 576 street children who were
      evaluated by 15 examiners. Using multi-stage sampling, twenty-seven different
      areas of Tehran were divided into 5 clusters and the children were selected
      randomly from each cluster. The two questionnaires applied included a demographic
      questionnaire and a questionnaire about high-risk behaviors such as substance
      use, alcohol consumption, cigarette smoking, etc. RESULTS: There was a
      statistical significant association between the length of work time and two
      variables: sex and economic status of family (p < 0.05). Incarceration history of
      street children who had lost both their parents and their parents had been
      divorced was significantly higher than others (p < 0.05). CONCLUSION: The street
      children's lifestyle is a risk factor for affecting them to variety types of
      socio-mental problems. Statistical significant association between parental
      divorces or the loss of both parents with a history of conviction mentions the
      important role of parents in transmitting moral and social values to children.

PMID- 25053963
TI  - Preoperative anxiety in candidates for heart surgery.
AB  - OBJECTIVE: The goal of this study was to evaluate preoperative anxiety and its
      predisposing factors in a group of adult patients who were candidate for any kind
      of heart surgery. METHODS: We evaluated preoperative anxiety in 300 patients
      undergoing heart surgery whose ages ranged between 18-65 years. Relationship of
      probable demographic factors like gender, educational level, marital status,
      number of children, family support, opium addiction, occupational status, and
      left ventricular ejection fraction (LVEF) with anxiety level of the patients were
      evaluated. To determine anxiety, the State-Trait Anxiety Inventory (STAI) was
      completed by the subjects. RESULTS: Descriptive anxiety levels showed that mean
      of state and trait anxiety of our studied patients were in moderate scaling.
      Correlation between state and trait anxiety was more prominent in females (r =
      0.80) than in males (r = 0.70) (p < 0.001). Distribution of males and females was
      significantly different (p = 0.048). All the patients had significantly different
      underlying diseases (p = 0.018), opioid addiction (yes/no) was significantly
      different in all of the patients (p < 0.001), while family support (yes/no) was
      not significantly different in all of the patients (p = 0.453). There were
      significant differences between mean of preoperative anxiety at different LVEF
      values of any EF level (p < 0.001, F = 6.47); those who had LVEF of more than 50%
      had significantly lower mean anxiety scores. CONCLUSION: Preoperative psychiatric
      consultation should be focused more on women and patients with higher EF.
      Moreover, physical activity strength may be effective on reducing preoperative
      anxiety.

PMID- 25053964
TI  - Farsi version of social skills rating system-secondary student form: cultural
      adaptation, reliability and construct validity.
AB  - OBJECTIVE: Assessment of social skills is a necessary requirement to develop and
      evaluate the effectiveness of cognitive and behavioral interventions. This paper
      reports the cultural adaptation and psychometric properties of the Farsi version
      of the social skills rating system-secondary students form (SSRS-SS)
      questionnaire (Gresham and Elliot, 1990), in a normative sample of secondary
      school students. METHODS: A two-phase design was used that phase 1 consisted of
      the linguistic adaptation and in phase 2, using cross-sectional sample survey
      data, the construct validity and reliability of the Farsi version of the SSRS-SS
      were examined in a sample of 724 adolescents aged from 13 to 19 years. RESULTS:
      Content validity index was excellent, and the floor/ceiling effects were low.
      After deleting five of the original SSRS-SS items, the findings gave support for
      the item convergent and divergent validity. Factor analysis revealed four
      subscales. RESULTS showed good internal consistency (0.89) and temporal stability
      (0.91) for the total scale score. CONCLUSION: Findings demonstrated support for
      the use of the 27-item Farsi version in the school setting. Directions for future
      research regarding the applicability of the scale in other settings and
      populations of adolescents are discussed.

PMID- 25053965
TI  - Self-immolation Among Medical Practitioners and Medical Students: More Evidence
      is Needed from Developing Countries.

PMID- 25053966
TI  - Antihyperglycemic and Anti-Inflammatory Effects of Standardized Curcuma
      xanthorrhiza Roxb. Extract and Its Active Compound Xanthorrhizol in High-Fat Diet
      Induced Obese Mice.
AB  - Xanthorrhizol, a natural compound isolated from Curcuma xanthorrhiza Roxb. (Java
      turmeric), has been reported to possess antioxidant and anticancer properties;
      however, its effects on metabolic disorders remain unknown. The aim of the
      present study was to evaluate the effects of xanthorrhizol (XAN) and C.
      xanthorrhiza extract (CXE) with standardized XAN on hyperglycemia and
      inflammatory markers in high-fat diet- (HFD-) induced obese mice. Treatment with
      XAN (10 or 25 mg/kg/day) or CXE (50 or 100 mg/kg/day) significantly decreased
      fasting and postprandial blood glucose levels in HFD-induced obese mice. XAN and
      CXE treatments also lowered insulin, glucose, free fatty acid (FFA), and
      triglyceride (TG) levels in serum. Epididymal fat pad and adipocyte size were
      decreased by high doses of XAN (26.6% and 20.1%) and CXE (25.8% and 22.5%),
      respectively. XAN and CXE treatment also suppressed the development of fatty
      liver by decreasing liver fat accumulation. Moreover, XAN and CXE significantly
      inhibited production of inflammatory cytokines, such as tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and C
      reactive protein (CRP) in adipose tissue (27.8-82.7%), liver (43.9-84.7%), and
      muscle (65.2-92.5%). Overall, these results suggest that XAN and CXE, with their
      antihyperglycemic and anti-inflammatory activities, might be used as potent
      antidiabetic agents for the treatment of type 2 diabetes. 

PMID- 25053967
TI  - No evidence for assortative mating within a willow warbler migratory divide.
AB  - INTRODUCTION: In contact zones, genetic mixing of two taxa can be restricted by
      prezygotic (e.g. assortative mating) or postzygotic (lower fitness of hybrid
      offspring) barriers, or a combination of the two. A hybrid zone between two
      willow warbler subspecies (Phylloscopus trochilus trochilus, P. t. acredula) with
      distinctive migratory strategies occurs in central Sweden. These subspecies
      exhibit differences in migratory direction and distance, resulting in
      geographically distinct wintering areas in Africa. The subspecies may have
      diverged from a common refuge after the last ice age, and neutral genetic markers
      are homogeneous across their range. By contrast, several phenotypic traits and
      genetic markers of two chromosomal regions previously identified show steep
      clines across the divide. The evolutionary forces that maintain this migratory
      divide remain unknown. Here we use plumage colour, morphology, genetic markers
      and feather stable nitrogen-isotopes (delta (15)N) to assess if assortative
      mating between migratory phenotypes could be acting as a possible mechanism for
      keeping the two forms genetically separate and maintaining the migratory divide.
      We colour-ringed a willow warbler breeding population in the central part of the
      hybrid zone and observed the breeding population to assess phenotypic and
      genotypic traits of social pairs. RESULTS: Our data suggest that wintering area
      and genetic ancestry had an effect on male arrival time to the breeding grounds
      which could contribute to assortment. However, evidence for assortative mating
      could not be detected based on a comparison of plumage colour, morphology and
      delta (15)N between social mates. CONCLUSION: This finding was strengthened by
      analyses of subspecies-specific genetic markers, which allowed us to identify the
      presence of a large proportion of potential hybrids and backcrosses at the study
      site. Our results supported the hypothesis that pre-mating isolation in willow
      warblers is weak, resulting in extensive hybridisation across the migratory
      divide.

PMID- 25053969
TI  - Protocol: a simple method for extracting next-generation sequencing quality
      genomic DNA from recalcitrant plant species.
AB  - Next-generation sequencing technologies rely on high quality DNA that is suitable
      for library preparation followed by sequencing. Some plant species store large
      amounts of phenolics and polysaccharides within their leaf tissue making genomic
      DNA extraction difficult. While many DNA extraction methods exist that contend
      with the presence of phenolics and polysaccharides, these methods rely on long
      incubations, multiple precipitations or commercially available kits to produce
      high molecular weight and contaminant-free DNA. In this protocol, we describe
      simple modifications to the established CTAB- based extraction method that allows
      for reliable isolation of high molecular weight genomic DNA from difficult to
      isolate plant species Corymbia (a eucalypt) and Coffea (coffee). The simplified
      protocol does not require multiple clean up steps or commercial based kits, and
      the isolated DNA passed stringent quality control standards for whole genome
      sequencing on Illumina HiSeq and TruSeq sequencing platforms. 

PMID- 25053968
TI  - Antidepressant treatment response is modulated by genetic and environmental
      factors and their interactions.
AB  - Although there is a wide variety of antidepressants with different mechanisms of
      action available, the efficacy of treatment is not satisfactory. Genetic factors
      are presumed to play a role in differences in medication response; however,
      available evidence is controversial. Even genome-wide association studies failed
      to identify genes or regions which would consequently influence treatment
      response. We conducted a literature review in order to uncover possible
      mechanisms concealing the direct effects of genetic variants, focusing mainly on
      reports from large-scale studies including STAR*D or GENDEP. We observed that
      inclusion of environmental factors, gene-environment and gene-gene interactions
      in the model improves the probability of identifying genetic modulator effects of
      antidepressant response. It could be difficult to determine which allele of a
      polymorphism is the risk factor for poor treatment outcome because depending on
      the acting environmental factors different alleles could be advantageous to
      improve treatment response. Moreover, genetic variants tend to show better
      association with certain intermediate phenotypes linked to depression because
      these are more objective and detectable than traditional treatment outcomes.
      Thus, detailed modeling of environmental factors and their interactions with
      different genetic pathways could significantly improve our understanding of
      antidepressant efficacy. In addition, the complexity of depression itself demands
      a more comprehensive analysis of symptom trajectories if we are to extract useful
      information which could be used in the personalization of antidepressant
      treatment. 

PMID- 25053970
TI  - Rapid fluorescent reporter quantification by leaf disc analysis and its
      application in plant-virus studies.
AB  - BACKGROUND: Fluorescent proteins are extraordinary tools for biology studies due
      to their versatility; they are used extensively to improve comprehension of plant
      microbe interactions. The viral infection process can easily be tracked and
      imaged in a plant with fluorescent protein-tagged viruses. In plants, fluorescent
      protein genes are among the most commonly used reporters in transient RNA
      silencing and heterologous protein expression assays. Fluorescence intensity is
      used to quantify fluorescent protein accumulation by image analysis or
      spectroscopy of protein extracts; however, these methods might not be suitable
      for medium- to large-scale comparisons. RESULTS: We report that laser scanners,
      used routinely in proteomic studies, are suitable for quantitative imaging of
      plant leaves that express different fluorescent protein pairs. We developed a
      microtiter plate fluorescence spectroscopy method for direct quantitative
      comparison of fluorescent protein accumulation in intact leaf discs. We used this
      technique to measure a fluorescent reporter in a transient RNA silencing
      suppression assay, and also to monitor early amplification dynamics of a
      fluorescent protein-labeled potyvirus. CONCLUSIONS: Laser scanners allow dual
      color fluorescence imaging of leaf samples, which might not be acquired in
      standard stereomicroscope devices. Fluorescence microtiter plate analysis of
      intact leaf discs can be used for rapid, accurate quantitative comparison of
      fluorescent protein accumulation.

PMID- 25053971
TI  - Not assessing the efficiency of multiple sequence alignment programs.
AB  - One can search for messages in the digits of pi or a Kazakhstan telephone book,
      but there may be hidden messages closer to home. A recent publication in this
      journal purportedly compared a set of multiple sequence alignment programs. The
      real purpose of the article may have been to remind readers how to present
      scientific data. 

PMID- 25053972
TI  - Invasive cervical cancers from women living in the United States or Botswana:
      differences in human papillomavirus type distribution.
AB  - BACKGROUND: Cervical cancer is the primary cause of cancer-related deaths in
      women living in Botswana. METHODS: Paraffin-embedded blocks of formalin-fixed
      invasive cervical cancer specimens were identified from women living in the U.S.
      (n = 50) or Botswana (n = 171) from which DNA was extracted. Thin-section PCR was
      performed on each sample for HPV types and HIV. Comparisons were made between HPV
      types and groups of types identified in cancers. RESULTS: HPV DNA was identified
      in 92.0% of specimens from the U.S. containing amplifiable human DNA, and 79.5%
      of specimens from Botswana. HPV 16 was detected in 40 of 46 HPV-positive
      specimens (87.0%) from the U.S. vs. 58 of 136 (42.7%) from Botswana (p < 0.001).
      In contrast, non-HPV 16/18 types, all A9 species (HPV16, 31, 33, 35, 52, and 58),
      non-HPV 16 A9 (HPV 31, 33, 35, 52, and 58), HPV 18, all A7 types (18, 39, 45, 59,
      and 68) types were detected significantly more often in specimens from Botswana.
      The prevalence of non-HPV 18 A7 types did not differ significantly between the
      two groups. For specimens from Botswana, 31.6% contained PCR-amplifiable HIV
      sequences, compared to 3.9% in U.S. specimens. Stratifying the samples from
      Botswana by HIV status, HPV 31 was detected significantly more often in HIV
      positive specimens. Other HPV types and groups of types were not significantly
      different between HIV-positive and HIV-negative specimens from Botswana.
      CONCLUSION: This study demonstrates that there may be important HPV type
      differences in invasive cervical cancers occurring in women living in the United
      States or Botswana. Factors in addition to HIV may be driving these differences.

PMID- 25053973
TI  - A dedicated database system for handling multi-level data in systems biology.
AB  - BACKGROUND: Advances in high-throughput technologies have enabled extensive
      generation of multi-level omics data. These data are crucial for systems biology
      research, though they are complex, heterogeneous, highly dynamic, incomplete and
      distributed among public databases. This leads to difficulties in data
      accessibility and often results in errors when data are merged and integrated
      from varied resources. Therefore, integration and management of systems
      biological data remain very challenging. METHODS: To overcome this, we designed
      and developed a dedicated database system that can serve and solve the vital
      issues in data management and hereby facilitate data integration, modeling and
      analysis in systems biology within a sole database. In addition, a yeast data
      repository was implemented as an integrated database environment which is
      operated by the database system. Two applications were implemented to demonstrate
      extensibility and utilization of the system. Both illustrate how the user can
      access the database via the web query function and implemented scripts. These
      scripts are specific for two sample cases: 1) Detecting the pheromone pathway in
      protein interaction networks; and 2) Finding metabolic reactions regulated by
      Snf1 kinase. RESULTS AND CONCLUSION: In this study we present the design of
      database system which offers an extensible environment to efficiently capture the
      majority of biological entities and relations encountered in systems biology.
      Critical functions and control processes were designed and implemented to ensure
      consistent, efficient, secure and reliable transactions. The two sample cases on
      the yeast integrated data clearly demonstrate the value of a sole database
      environment for systems biology research.

PMID- 25053974
TI  - Description of a large measles epidemic in Democratic Republic of Congo, 2010
      2013.
AB  - BACKGROUND: Although measles mortality has declined dramatically in Sub-Saharan
      Africa, measles remains a major public health problem in countries like the
      Democratic Republic of Congo (DRC). Here, we describe the large measles epidemic
      that occurred in the Democratic Republic of Congo between 2010 and 2013 using
      data from the national surveillance system as well as vaccine coverage surveys to
      provide a snapshot of the epidemiology of measles in DRC. METHODS: Standardized
      national surveillance data were used to describe measles cases from 2010 to 2013.
      Attack rates and case fatality ratios were calculated and the temporal and
      spatial evolution of the epidemic described. Data on laboratory confirmation and
      vaccination coverage surveys as a part of routine program monitoring are also
      presented. FINDINGS: Between week 1 of 2010 and week 45 of 2013, a total of
      294,455 cases and 5,045 deaths were reported. The cumulative attack rate (AR) was
      0.4%. The Case Fatality Ratio (CFR) was 1.7% among cases reported in health
      structures through national surveillance. A total of 186,178 cases (63%) were
      under 5 years old, representing an estimated AR of 1.4% in this age group.
      Following the first mass vaccination campaigns, weekly reported cases decreased
      by 21.5%. Results of post-vaccination campaign coverage surveys indicated sub
      optimal (under 95%) vaccination coverage among children surveyed. CONCLUSIONS:
      The data reported here highlight the need to seek additional means to reinforce
      routine immunization as well as ensure the timely implementation of Supplementary
      Immunization Activities to prevent large and repeated measles epidemics in DRC.
      Although reactive campaigns were conducted in response to the epidemic,
      strategies to ensure that children are vaccinated in the routine system remains
      the foundation of measles control.

PMID- 25053975
TI  - Attitudes towards people with mental illness among psychiatrists, psychiatric
      nurses, involved family members and the general population in a large city in
      Guangzhou, China.
AB  - PURPOSE: Stigma towards people with mental illness is believed to be widespread
      in low and middle income countries. METHODS: This study assessed the attitudes
      towards people with mental illness among psychiatrists, psychiatric nurses,
      involved family members of patients in a psychiatric facility and the general
      public using a standard 43-item survey (N = 535). Exploratory factor analysis
      identified four distinctive attitudes which were then compared using Analysis of
      Covariance (ANCOVA) among the four groups, all with ties to the largest
      psychiatric facility in Guangzhou, China, adjusting for sociodemographic
      differences. RESULTS: Four uncorrelated factors expressed preferences for 1)
      community-based treatment, social integration and a biopsychosocial model of
      causation, 2) direct personal relationships with people with mental illness, 3) a
      lack of fear and positive views of personal interactions with people with mental
      illness, 4) disbelief in superstitious explanations of mental illness.
      Statistically significant differences favored community-based treatment and
      biopsychosocial causation (factor 1) among professional groups (psychiatrists and
      nurses) as compared with family members and the general public (p < 0.001); while
      family members, unexpectedly, showed far weaker personal preferences for direct
      personal relationships with people with mental illness than all three other
      groups (p < 0.001). CONCLUSION: Both psychiatrists and nurses showed greater
      support for social integration and biopsychosocial understandings of mental
      illness than the lay public, most likely because of their training and
      experience, while family members showed the least positive attitudes towards
      direct personal relationships with people with mental illness. These findings
      suggest support for a more extensive, formal system of care that gives family
      members some distance from the problems of their relatives and support in their
      care.

PMID- 25053976
TI  - A rapid appraisal of access to and utilisation of psychotropic medicines in
      Bihar, India.
AB  - BACKGROUND: A major aspect of providing mental healthcare is access to and use of
      psychotropic medications. Bihar is a state in northeast India with limited mental
      healthcare provision; consequently access to and utilisation of psychotropic
      medications are likely to be limited. However, to date there has been no research
      assessing the situation. This study therefore aims to analyse the psychotropic
      medications management cycle (selection, procurement, distribution and use), and
      identify the barriers to access and utilisation, and their underlying causes.
      METHOD: A rapid appraisal method was used in which primary and secondary data
      sources were collected and analysed. Semi-structured interviews were conducted
      with twenty-two stakeholders and twenty-one service users from the government,
      non-governmental organisation (NGO) and private sectors. The qualitative data
      collected was analysed using a comparative thematic approach. The research was
      supported by the NGOs BasicNeeds and Nav Bharat Jagriti Kendra. RESULTS:
      Availability, distance and cost were the main barriers to access and utilisation.
      At the medical college hospital level a lack of supply appears to be due to a
      discrepancy between orders made by the hospital and medications supplied by the
      manufacturers. At the primary health centre and district hospital level the main
      barrier is a cycle between lack of demand for treatments for mental illness by
      doctors and patients. CONCLUSION: Further investigation and monitoring is
      necessary to ensure the availability of psychotropic medications at the medical
      college hospital level. In addition, implementation of the District Mental Health
      Programme is likely to address the access and utilisation barriers due to its
      potential to break the current cycle of lack of demand.

PMID- 25053978
TI  - Multiscale Modeling of Flow Induced Thrombogenicity With Dissipative Particle
      Dynamics and Molecular Dynamics.

PMID- 25053977
TI  - Lineage-specific regulation of imprinted X inactivation in extraembryonic
      endoderm stem cells.
AB  - BACKGROUND: Silencing of the paternal X chromosome (Xp), a phenomenon known as
      imprinted X-chromosome inactivation (I-XCI), characterises, amongst mouse
      extraembryonic lineages, the primitive endoderm and the extraembryonic endoderm
      (XEN) stem cells derived from it. RESULTS: Using a combination of chromatin
      immunoprecipitation characterisation of histone modifications and single-cell
      expression studies, we show that whilst the Xp in XEN cells, like the inactive X
      chromosome in other cell types, globally accumulates the repressive histone mark
      H3K27me3, a large number of Xp genes locally lack H3K27me3 and escape from I-XCI.
      In most cases this escape is specific to the XEN cell lineage. Importantly, the
      degree of escape and the genes concerned remain unchanged upon XEN conversion
      into visceral endoderm, suggesting stringent control of I-XCI in XEN derivatives.
      Surprisingly, chemical inhibition of EZH2, a member of the Polycomb repressive
      complex 2 (PRC2), and subsequent loss of H3K27me3 on the Xp, do not drastically
      perturb the pattern of silencing of Xp genes in XEN cells. CONCLUSIONS: The
      observations that we report here suggest that the maintenance of gene expression
      profiles of the inactive Xp in XEN cells involves a tissue-specific mechanism
      that acts partly independently of PRC2 catalytic activity.

PMID- 25053979
TI  - The role of topical antifungal therapy for onychomycosis and the emergence of
      newer agents.
AB  - Onychomycosis is a common infection of the nail unit that is usually caused by a
      dermatophyte (tinea unguium) and most frequently affects toenails in adults. In
      most cases, onychomycosis is associated with limited treatment options that are
      effective in achieving complete clearance in many cases. In addition, recurrence
      rates are high in the subset of treated patients who have been effectively
      cleared, usually with an oral antifungal agent. There has been a conspicuous
      absence of medical therapies approved in the United States since the introduction
      of topical ciclopirox (8% nail lacquer), with no new effective agents introduced
      for more than 10 years. Fortunately, newer agents and formulations have been
      under formal development. While patients might prefer a topical therapy, efficacy
      with ciclopirox 8% nail lacquer, the only available agent until the very recent
      approval of efinaconazole 10% solution, has been disappointing. The poor
      therapeutic outcomes achieved with ciclopirox 8% nail lacquer were not unexpected
      as the cure rates achieved in the clinical trials were unimpressive, despite
      concomitant nail debridement, which was an integral part of the pivotal trials
      with ciclopirox 8% nail lacquer. Efinaconazole 10% solution and tavaborole 5%
      solution are new topical antifungals specifically developed for the treatment of
      dermatophyte onychomycosis. In Phase 3 clinical trials, both newer agents were
      applied once daily for 48 weeks without concomitant nail debridement. Mycologic
      cure rates with efinaconazole 10% solution are markedly superior to what was
      achieved with ciclopirox 8% nail lacquer. To add, they appear to be nearly
      comparable to those achieved with oral itraconazole in pivotal clinical trials.
      However, it is important to remember that direct comparisons between different
      studies are not conclusive, are not generally considered to be scientifically
      sound, and may not be entirely accurate due to differences in study design and
      other factors. Well-designed and properly powered head-to-head studies are needed
      in order to draw definitive conclusions about efficacy comparisons between
      therapies, at least based on academic and regulatory standards. Although
      tavaborole 5% solution is in an earlier phase of development for onychomycosis,
      treatment success rates reported thus far for both efinaconazole 10% solution and
      tavaborole 5% solution are superior to ciclopirox 8% nail lacquer. As a result, a
      new era of onychomycosis appears to be upon us that incorporates topical therapy
      more effectively than in the past. Not only may these newer topical agents
      provide viable monotherapy alternatives to oral therapy for onychomycosis,
      topical therapy for onychomycosis that is effective, well tolerated, and easy to
      use may also find a role in combination therapy, and/or as continued therapy
      after initial clearance to reduce recurrence or re-infection. 

PMID- 25053980
TI  - Racial differences in clinical characteristics, perceptions and behaviors, and
      psychosocial impact of adult female acne.
AB  - OBJECTIVE: Limited data are available on racial differences in clinical
      characteristics and burden in adult female acne. The objective was to describe
      racial differences in clinical characteristics, psychosocial impact, perceptions,
      behaviors, and treatment satisfaction in facial adult female acne. DESIGN: Cross
      sectional, web-based survey. SETTING: Diverse sample of United States women.
      PARTICIPANTS: Women between the ages of 25 and 45 years with facial acne (>=25
      visible lesions). MEASUREMENTS: Outcomes included sociodemographic
      characteristics, psychosocial impacts, perceptions, behaviors, and treatment
      satisfaction. Racial differences were evaluated using descriptive statistics and
      t-test/chi-square analyses. RESULTS: 208 females participated (mean age 35+/-6
      years); 51.4 percent were White/Caucasian and 48.6 percent were non
      White/Caucasian women [Black/African American (n=51); Hispanic/Latina (n=23);
      Asian (n=16); Other (n=ll)]. Age of acne onset (mean 14.8+/-5 vs. 17.0+/-8 years,
      p<0.05) and acne concern occurred earlier (16.6+/-7 vs. 19.3+/-9 years, p<0.05)
      in White/Caucasian than non-White/Caucasian subjects. Facial acne primarily
      presented on chin (28.0%) and cheeks (30.8%) for White/Caucasian women versus
      cheeks (58.4%) for non-White/Caucasian women. Non-White/Caucasian women
      experienced more postinflammatory hyperpigmentation than White/Caucasian women
      (p<0.0001). Facial acne negatively affected quality of life (QoL) in both groups,
      and most participants (>70%) reported some depression/anxiety symptoms. More
      White/Caucasian than non-White/Caucasian women were troubled by facial acne
      (88.8% vs. 76.2%, p<0.05). Lesion clearance was most important to White/Caucasian
      women (57.9 vs. non-White/Caucasian 31.7%, p<0.001); non-White/Caucasian females
      focused on postinflammatory hyperpigmentation clearance (41.6% vs. Caucasian
      8.4%, p<0.0001). CONCLUSION: RESULTS highlight racial differences in participant
      reported clinical characteristics, attitudes, behaviors, and treatment
      satisfaction. These findings may inform clinicians about racial differences in
      facial adult female acne and guide treatment recommendations toward improving
      care.

PMID- 25053981
TI  - Retapamulin 1% Ointment and Clobetasol Propionate 0.05% Foam is More Efficacious
      than Vehicle Ointment and Clobetasol 0.05% Propionate Foam in the Treatment of
      Hand/Foot Dermatitis: A Single Center, Randomized, Double-blind Study.
AB  - BACKGROUND: Staphylococcus aureus has been implicated in the pathogenesis of
      adult hand/foot dermatitis. OBJECTIVE: The authors hypothesized that retapamulin
      1% ointment and clobetasol propionate 0.05% foam would decrease disease severity
      in subjects with hand/foot dermatitis and provide a higher clearance of
      Staphylococcus aureus colonization, when compared to vehicle (placebo) ointment
      and clobetasol propionate 0.05% foam. METHODS: Adult subjects with moderate to
      very severe hand/foot dermatitis had twice-daily topical application of
      clobetasol propionate 0.05% foam to hands/feet for 14 days and were randomized to
      apply either retapamulin 1% ointment or vehicle ointment twice daily to
      hands/feet and nares for five days. RESULTS: Seventy-three percent of subjects in
      the retapamulin/clobetasol group were clear/almost clear at Day 15 compared to 47
      percent of subjects in the vehicle/clobetasol group (p-value of 0.04). The
      percentage of subjects who had both negative skin and nares cultures and were
      clear/almost clear was also statistically significant in favor of the
      retapamulin/clobetasol group at Day 15 (p-value of 0.05). LIMITATIONS: Sample
      size, study population. CONCLUSION: At Day 15, retapamulin 1% ointment with
      clobetasol propionate 0.05% foam was more efficacious than vehicle ointment and
      clobetasol propionate 0.05% foam for disease improvement and Staphylococcus
      aureus clearance in adult subjects with hand/foot dermatitis.

PMID- 25053982
TI  - Beta blockers: an innovation in the treatment of infantile hemangiomas.
AB  - Infantile hemangiomas are benign vascular tumors seen in 4.5 percent of neonates
      and infants. While most infantile hemangiomas can be managed with active
      nonintervention, a subset of patients will require more aggressive management.
      Here the authors review the use of beta-blockers in the treatment of infantile
      hemangiomas, including oral, topical, and multimodal treatment options. They
      discuss the latest data on propranolol, including criteria for patient selection,
      dosing recommendations, and appropriate monitoring for side effects and efficacy.
      Lastly, they review indications for topical timolol treatment and the potential
      benefits of concomitant laser therapy. 

PMID- 25053983
TI  - Diet and dermatology: the role of dietary intervention in skin disease.
AB  - For decades, it was thought that many common dermatological conditions had no
      relationship to diet. Studies from recent years, however, have made it clear that
      diet may influence outcome. In this review, the authors focus on conditions for
      which the role of diet has traditionally been an underappreciated aspect of
      therapy. In some cases, dietary interventions may influence the course of the
      skin disease, as in acne. In others, dietary change may serve as one aspect of
      prevention, such as in skin cancer and aging of the skin. In others,
      dermatological disease may be linked to systemic disease, and dietary changes may
      affect health outcomes, as in psoriasis. Lastly, systemic medications prescribed
      for dermatological disease, such as steroids, are known to raise the risk of
      other diseases, and dietary change may reduce this risk. 

PMID- 25053984
TI  - Chromatin-mediated microtubule nucleation in Drosophila syncytial embryos.
AB  - Upon entry into mitosis, many microtubules are nucleated that coordinately
      integrate into a stable, yet dynamic, mitotic spindle apparatus. In a recent
      publication, we examined microtubule-generating pathways within a single model
      system, the Drosophila syncytial embryo. We found that, following
      depolymerisation of metaphase spindle microtubules by cold treatment, spindles
      regenerate predominantly from microtubules nucleated within the vicinity of
      chromatin. We also showed this chromatin-mediated microtubule nucleation is
      mediated by the Drosophila homolog of a vertebrate spindle assembly factor (SAF),
      HURP and is dependent on the conserved microtubule amplifying protein complex,
      Augmin. Here, we expand our investigation into Drosophila SAFs, providing
      evidence that, in vitro, both D-HURP and D-TPX2 are able to bind to and stabilize
      microtubules. We show that GFP-D-HURP purified from embryos interacts with
      Importin-beta and Augmin and, consistent with this, demonstrate that the
      underlying basis of chromatin-mediated microtubule nucleation in Drosophila
      syncytial embryos is dependent on Ran-GTP. 

PMID- 25053985
TI  - The role of F-actin in modulating Clathrin-mediated endocytosis: Lessons from
      neurons in health and neuropsychiatric disorder.
AB  - Clathrin-mediated endocytosis is one of several mechanisms for retrieving
      transmembrane proteins from the cell surface. This key mechanism is highly
      conserved in evolution and is found in any eukaryotic cell from yeast to mammals.
      Studies from several model organisms have revealed that filamentous actin (F
      actin) plays multiple distinct roles in shaping Clathrin-mediated endocytosis.
      Yet, despite the identification of numerous molecules at the interface between
      endocytic machinery and the cytoskeleton, our mechanistic understanding of how F
      actin regulates endocytosis remains limited. Key insights come from neurons where
      vesicular release and internalization are critical to pre- and postsynaptic
      function. Recent evidence from human genetics puts postsynaptic organization,
      glutamate receptor trafficking, and F-actin remodeling in the spotlight as
      candidate mechanisms underlying neuropsychiatric disorders. Here I review recent
      findings that connect the F-actin cytoskeleton mechanistically to Clathrin
      mediated endocytosis in the central nervous system, and discuss their potential
      involvement in conferring risk for neuropsychiatric disorder. 

PMID- 25053986
TI  - Role of YY1 in the pathogenesis of prostate cancer and correlation with
      bioinformatic data sets of gene expression.
AB  - Current treatments of various cancers include chemotherapy, radiation, surgery,
      immunotherapy, and combinations. However, there is a need to develop novel
      diagnostic and therapeutic treatments for unresponsive patients. These may be
      achieved by the identification of novel diagnostic and prognostic biomarkers
      which will help in the stratification of patients' initial responses to
      particular treatments and circumvent resistance, relapses, metastasis, and death.
      We have been investigating human prostate cancer as a model tumor. We have
      identified Yin Yang 1 (YY1), a dysregulated transcription factor, whose
      overexpression correlated with tumor progression as well as in the regulation of
      drug resistance and the development of EMT. YY1 expression is upregulated in
      human prostate cancer cell lines and tissues. We postulated that YY1 may be a
      potential biomarker in prostate cancer for patients' stratification as well as a
      novel target for therapeutic intervention. We used Bioinformatic gene RNA array
      datasets for the expression of YY1 in prostate tumor tissues as compared to
      normal tissues. Interestingly, variations on the expression levels of YY1 mRNA in
      prostate cancer were reported by different investigators. This mini review
      summarizes the current reported studies and Bioinformatic analyses on the role of
      YY1 in the pathogenesis of prostate cancer. 

PMID- 25053987
TI  - Hax-1 is required for Rac1-Cortactin interaction and ovarian carcinoma cell
      migration.
AB  - Hax-1 is a multifunctional protein, which is involved in diverse cellular
      signaling pathways including tumor cell survival and migration. We have shown
      previously that cell migration stimulated by the oncogenic G protein, G13,
      requires Hax-1 for the formation of a functional complex involving Galpha13,
      Rac1, and cortactin. However, the role of Hax-1 in cancer cell migration or its
      role in Rac1-cortactin complex formation, which is known to be required for such
      migration remains to be characterized. Results focused on resolving the role of
      Hax-1 in ovarian cancer pathophysiology indicate that Hax-1 is overexpressed in
      ovarian cancer cells and the silencing of Hax-1 inhibits lysophosphatidic acid
      (LPA)- or fetal bovine serum-stimulated migration of these cells. In addition,
      silencing of Hax-1 greatly reduces Rac1-cortactin interaction and their
      colocalization in SKOV3 cells. Mapping the structural domains of Hax-1 indicates
      that it interacts with cortactin via domains spanning amino acids 1 to 56 (Hax
      D1) and amino acids 113 to 168 (Hax-D3). Much weaker interaction with cortactin
      was also observed with the region of Hax-1 spanning amino acids 169 - 224 (Hax
      D4). Similar mapping of Hax-1 domains involved in Rac1 interaction indicates that
      it associates with Rac1 via two primary domains spanning amino acids 57 to 112
      (Hax-D2) and 169 to 224 (Hax-D4). Furthermore, expression of either of these
      domains inhibits LPA-mediated migration of SKOV3 cells, possibly through their
      ability to exert competitive inhibition on endogenous Hax-1-Rac1 and/or Hax-1
      cortactin interaction. More significantly, expression of Hax-D4 drastically
      reduces Rac1-cortactin colocalization in SKOV3 cells along with an attenuation of
      LPA-stimulated migration. Thus our results presented here describe for the first
      time that Hax-1 interaction is required for the association between Rac1 and
      cortactin and that these multiple interactions are required for the LPA
      stimulated migration of SKOV3 ovarian cancer cells. 

PMID- 25053988
TI  - Hexokinase II inhibitor, 3-BrPA induced autophagy by stimulating ROS formation in
      human breast cancer cells.
AB  - Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in
      cancer cells. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, has been proposed
      as a specific antitumor agent. Autophagy is a process that regulates the balance
      between protein synthesis and protein degradation. Autophagy in mammalian systems
      occurs under basal conditions and can be stimulated by stresses, including
      starvation, oxidative stress. Therefore, we hypothesized that 3-BrPA could induce
      autophagy. In the present study, we explored the mechanism of 3-BrPA and its
      combined action with chloroquine. Our results demonstrate that in MDA-MB-435 and
      in MDA-MB-231 cells, 3-BrPA induces autophagy, which can be inhibited by
      chloroquine. Furthermore, the combined treatment synergistically decreased the
      number of viable cells. Interestingly, the combined treatment triggered apoptosis
      in MDA-MB-435 cells, while it induced necroptosis in MDA-MB-231 cells. ROS
      mediated cell death when 3-BrPA and CQ were co-administered. Finally, CQ enhanced
      the anticancer efficacy of 3-BrPA in vivo. Collectively, our results show that 3
      BrPA triggers autophagy, increasing breast cancer cell resistance to 3-BrPA
      treatment and that CQ enhanced 3-BrPA-induced cell death in breast cancer cells
      by stimulating ROS formation. Thus, inhibition of autophagy may be an innovative
      strategy for adjuvant chemotherapy of breast cancer.human skeletal muscle.
      Efficient Mirk depletion in SU86.86 pancreatic cancer cells by an inducible shRNA
      decreased expression of eight antioxidant genes. Thus both cancer cells and
      differentiated myotubes utilize Mirk kinase to relieve oxidative stress. 

PMID- 25053989
TI  - Amphiregulin and PTEN evoke a multimodal mechanism of acquired resistance to PI3K
      inhibition.
AB  - Phosphoinositide-3 kinase (PI3K) signaling pathway alterations occur broadly in
      cancer and PI3K is a promising therapeutic target. Here, we investigated acquired
      resistance to GDC-0941, a PI3K inhibitor in clinical trials. Colorectal cancer
      (CRC) cells made to be resistant to GDC-0941 were discovered to secrete
      amphiregulin, which resulted in increased EGFR/MAPK signaling. Moreover,
      prolonged PI3K pathway inhibition in cultured cells over a period of months led
      to a secondary loss of PTEN in 40% of the CRC lines with acquired resistance to
      PI3K inhibition. In the absence of PI3K inhibitor, these PTEN-null PI3K inhibitor
      resistant clones had elevated PI3K pathway signaling and decreased sensitivity to
      MAPK pathway inhibitors. Importantly, PTEN loss was not able to induce resistance
      to PI3K inhibitors in the absence of amphiregulin, indicating a multimodal
      mechanism of acquired resistance. The combination of PI3K and MAPK pathway
      inhibitors overcame acquired resistance in vitro and in vivo. 

PMID- 25053990
TI  - Internal ribosome entry site of bFGF is the target of thalidomide for IMiDs
      development in multiple myeloma.
AB  - Although new analogues of immunomodulatory drugs (IMiDs) are being developed for
      MM, the molecular mechanism of these drugs remains unclear. In the current study,
      we used MM cell lines as a model to investigate the molecular mechanism of
      thalidomide and to compare its potency with IMiDs such as pomalidomide. We
      determined that thalidomide did not inhibit cell proliferation of RPMI8226 and
      U266 MM cells, whereas pomalidomide showed a significant inhibitory effect on
      these two MM cell lines. Interestingly, we further demonstrated that although
      thalidomide down-regulated bFGF translation through the inhibition of IRES even
      at 0.1 MUg/ml, pomalidomide did not have a similar affect bFGF levels. A colony
      formation assay demonstrated that thalidomide and the bFGF knock-down clones
      caused a significant reduction in the clonogenic ability of MM cells, and
      treatment with exogenous bFGF can recover the clonogenic ability of thalidomide
      treated cells and knock-down clones, but not that of pomalidomide-treated cells.
      This implies that thalidomide, but not pomalidomide, targets the IRES of FGF-2.
      In conclusion, our results highlight a non-cytotoxic anticancer drug target for
      thalidomide, the IRES of bFGF, and provide the mechanistic rationale for
      developing IMiDs as anti-cancer therapeutics in MM patients, with improved
      potency and fewer side effects. 

PMID- 25053991
TI  - Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative
      regulation of STEAP1 by post-transcriptional and post-translational mechanisms.
AB  - STEAP1 gene is overexpressed in several kinds of tumors, particularly in prostate
      cancer. Besides STEAP1, there is another related gene, STEAP1B, which may encode
      two different transcripts. Although several studies have been pointing STEAP1 as
      a putative immunotherapeutic target and biomarker, the mechanisms underlying its
      regulation are not fully understood. In silico analysis allowed us to show that
      STEAP1 and STEAP1B share high homology, but with slight differences at structural
      level. Experiments with prostate cells showed that STEAP1B2 is overexpressed in
      cancer cells. Regarding STEAP1 regulation, it is demonstrated that the stability
      of mRNA and protein is higher in LNCaP than in PNT1A cells. Of note, serum
      triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability,
      e.g., increasing it in PNT1A and decreasing in LNCaP. These results suggest that
      STEAP1 may be regulated by post-transcriptional and post-translational
      modifications (PTM), which may differ between non-neoplastic and neoplastic
      cells. These PTM are supported through in silico analysis, where several
      modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked
      beta-N-acetylglucosamine, may occur in STEAP1 protein. In conclusion, these data
      indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be
      involved in regulation of STEAP1 expression in prostate cells. 

PMID- 25053992
TI  - Effects of a novel cyclic RGD peptidomimetic on cell proliferation, migration and
      angiogenic activity in human endothelial cells.
AB  - BACKGROUND: Cyclic RGD peptidomimetics containing a bifunctional diketopiperazine
      scaffold are a novel class of high-affinity ligands for the integrins alphaVbeta3
      and alphaVbeta5. Since integrins are a promising target for the modulation of
      normal and pathological angiogenesis, the present study aimed at characterizing
      the ability of the RGD peptidomimetic cyclo[DKP-RGD] 1 proliferation, migration
      and network formation in human umbilical vein endothelial cells (HUVEC). METHODS:
      Cell viability was assessed by flow cytometry and annexin V (ANX)/propidium
      iodide (PI) staining. Cell proliferation was evaluated by the ELISA measurement
      of bromodeoxyuridine (BrdU) incorporation. Network formation by HUVEC cultured in
      Matrigel-coated plates was evaluated by optical microscopy and image analysis.
      Integrin subunit mRNA expression was assessed by real time-PCR and Akt
      phosphorylation by western blot analysis. RESULTS: Cyclo[DKP-RGD] 1 does not
      affect cell viability and proliferation either in resting conditions or in the
      presence of the pro-angiogenic growth factors VEGF, EGF, FGF, and IGF-I. Addition
      of cyclo[DKP-RGD] 1 however significantly decreased network formation induced by
      pro-angiogenic growth factors or by IL-8. Cyclo[DKP-RGD] 1 did not affect mRNA
      levels of alphaV, beta3 or beta5 integrin subunits, however it significantly
      reduced the phosphorylation of Akt. CONCLUSIONS: Cyclo[DKP-RGD] 1 can be a
      potential modulator of angiogenesis induced by different growth factors, possibly
      devoid of the adverse effects of cytotoxic RGD peptidomimetic analogues.

PMID- 25053993
TI  - Flow-regulated lymphatic vasculature development and signaling.
AB  - The role of blood flow in regulating signaling pathways and gene expression in
      the blood vasculature is well known. Recent studies have identified equally
      important roles of flow-mediated signaling in the lymphatic circulation including
      control of lymphatic vascular growth, remodeling, regeneration and maintenance of
      the lymphatic fate. In this review, we summarize these advances focusing on the
      role of fluid dynamics in control of lymphatic vasculature formation. 

PMID- 24795809
TI  - Case Report: retained gutta-percha as a cause for persistent maxillary sinusitis
      and pain.
AB  - Dental sources of infection can produce acute and chronic maxillary sinusitis. In
      some cases, the source of the infection may be related to the presence of
      endodontic materials in the oral cavity. In this article, we report a case of
      retained gutta-percha in the maxillary sinus resulting in chronic sinusitis. 

PMID- 25053995
TI  - Low coverage sequencing of two Asian elephant (Elephas maximus) genomes.
AB  - BACKGROUND: There are three species of elephant that exist, the Asian elephant
      (Elephas maximus) and two species of African elephant (Loxodonta africana and
      Loxodonta cyclotis). The populations of all three species are dwindling, and are
      under threat due to factors, such as habitat destruction and ivory hunting. The
      species differ in many respects, including in their morphology and response to
      disease. The availability of elephant genome sequence data from all three
      elephant species will complement studies of behaviour, genetic diversity,
      evolution and disease resistance. FINDINGS: We present low-coverage Illumina
      sequence data from two Asian elephants, representing approximately 5X and 2.5X
      coverage respectively. Both raw and aligned data are available, using the African
      elephant (L. africana) genome as a reference. CONCLUSIONS: The data presented
      here are an important addition to the available genetic and genomic information
      on Asian and African elephants.

PMID- 25053996
TI  - Comparison of cognitive and UHDRS measures in monitoring disease progression in
      Huntington's disease: a 12-month longitudinal study.
AB  - Progressive cognitive decline is a feature of Huntington's disease (HD), an
      inherited neurodegenerative movement disorder. Comprehensive neuropsychological
      testing is the 'gold standard' to establish cognitive status but is often
      impractical in time-constrained clinics. The study evaluated the utility of brief
      cognitive tests (MMSE and MoCA), UHDRS measures and a comprehensive
      neuropsychological tests battery in monitoring short-term disease progression in
      HD. Twenty-two manifest HD patients and 22 matched controls were assessed at
      baseline and 12-month. A linear mixed-effect model showed that although the HD
      group had minimal change in overall global cognition after 12 months, they did
      show a significant decline relative to the control group. The controls exhibited
      a practice effect in most of the cognitive domain scores over time. Cognitive
      decline at 12-month in HD was found in the executive function domain but the
      effect of this on global cognitive score was masked by the improvement in their
      language domain score. The varying practice effects by cognitive domain with
      repeated testing indicates the importance of comparing HD patients to control
      group in research trials and that cognitive progression over 12 months in HD
      should not be judged by changes in global cognitive score. The three brief
      cognitive tests effectively described cognition of HD patients on cross-sectional
      analysis. The UHDRS cognitive component, which focuses on testing executive
      function and had low variance over time, is a more reliable brief substitute for
      comprehensive neuropsychological testing than MMSE and MoCA in monitoring
      cognitive changes in HD patients after 12 months. 

PMID- 25053997
TI  - The liver transcriptome of two full-sibling Songliao black pigs with extreme
      differences in backfat thickness.
AB  - BACKGROUND: Fatness traits in animals are important for their growth, meat
      quality, reproductive performance, and immunity. The liver is the principal organ
      of the regulation of lipid metabolism, and this study used massive parallelized
      high-throughput sequencing technologies to determine the porcine liver tissue
      transcriptome architecture of two full-sibling Songliao black pigs harboring
      extremely different phenotypes of backfat thickness. RESULTS: The total number of
      reads produced for each sample was in the region of 53 million, and 8,226 novel
      transcripts were detected. Approximately 92 genes were differentially regulated
      in the liver tissue, while 31 spliced transcripts and 33 primary transcripts
      showed significantly differential expression between pigs with higher and lower
      backfat thickness. Genes that were differentially expressed were involved in the
      metabolism of various substances, small molecule biochemistry, and molecular
      transport. CONCLUSIONS: Genes involved in the regulation of lipids could play an
      important role in lipid and fatty acid metabolism in the liver. These results
      could help us understand how liver metabolism affects the backfat thickness of
      pigs.

PMID- 25053998
TI  - Characterization of the vaginal microbiota of healthy Canadian women through the
      menstrual cycle.
AB  - BACKGROUND: The vaginal microbial community plays a vital role in maintaining
      women's health. Understanding the precise bacterial composition is challenging
      because of the diverse and difficult-to-culture nature of many bacterial
      constituents, necessitating culture-independent methodology. During a natural
      menstrual cycle, physiological changes could have an impact on bacterial growth,
      colonization, and community structure. The objective of this study was to assess
      the stability of the vaginal microbiome of healthy Canadian women throughout a
      menstrual cycle by using cpn60-based microbiota analysis. Vaginal swabs from 27
      naturally cycling reproductive-age women were collected weekly through a single
      menstrual cycle. Polymerase chain reaction (PCR) was performed to amplify the
      universal target region of the cpn60 gene and generate amplicons representative
      of the microbial community. Amplicons were pyrosequenced, assembled into
      operational taxonomic units, and analyzed. Samples were also assayed for total
      16S rRNA gene content and Gardnerella vaginalis by quantitative PCR and screened
      for the presence of Mollicutes by using family and genus-specific PCR. RESULTS:
      Overall, the vaginal microbiome of most women remained relatively stable
      throughout the menstrual cycle, with little variation in diversity and only
      modest fluctuations in species richness. Microbiomes between women were more
      different than were those collected consecutively from individual women.
      Clustering of microbial profiles revealed the expected groupings dominated by
      Lactobacillus crispatus, Lactobacillus iners, and Lactobacillus jensenii.
      Interestingly, two additional clusters were dominated by either Bifidobacterium
      breve or a heterogeneous mixture of nonlactobacilli. Direct G. vaginalis
      quantification correlated strongly with its pyrosequencing-read abundance, and
      Mollicutes, including Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma
      urealyticum, were detected in most samples. CONCLUSIONS: Our cpn60-based
      investigation of the vaginal microbiome demonstrated that in healthy women most
      vaginal microbiomes remained stable through their menstrual cycle. Of interest in
      these findings was the presence of Bifidobacteriales beyond just Gardnerella
      species. Bifidobacteriales are frequently underrepresented in 16S rRNA gene-based
      studies, and their detection by cpn60-based investigation suggests that their
      significance in the vaginal community may be underappreciated.

PMID- 25053999
TI  - Neuroprotection of microRNA in neurological disorders (Review).
AB  - MicroRNAs (miRNAs) are small, endogenous, non-coding RNA molecules that function
      as post-transcriptional regulators of gene expression by imperfect base-pairing
      with the 3'-untranslated regions of their target mRNAs. Altered expression of
      numerous miRNAs has been shown to be extensively involved in the pathogenesis of
      various diseases and cancers. Additionally, the specific expression of miRNAs in
      the nervous system has indicated that miRNAs are critical for the occurrence and
      development of neurological diseases. Increasing evidence has shown that specific
      miRNAs target the expression of particular proteins that are significant in the
      disease pathogenesis. Therefore, miRNA-mediated regulation may be important in
      the occurrence and development of neurological diseases and may function as a
      novel biomarker and tool for clinical therapy. In the present study, the
      significance of miRNAs is reviewed in a number of neurological disorders and the
      possibility of their use in therapeutic interventions is evaluated.

PMID- 25054000
TI  - Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus.
AB  - Cytoglobin (Cygb), a novel oxygen-binding protein, is expressed in the majority
      of tissues and has been proposed to function in nitric oxide (NO) metabolism in
      the vasculature and to have cytoprotective properties. However, the overall
      functions of Cygb remain elusive. Cygb is also expressed in a subpopulation of
      brain neurons. Recently, it has been shown that stress upregulates Cygb
      expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)
      positive neurons, an enzyme that produces NO, co-express Cygb. However, there are
      more neurons expressing Cygb than nNOS, thus a large number of Cygb neurons
      remain uncharacterized by the neurochemical content. The aim of the present study
      was to provide an additional and more detailed neurochemical phenotype of Cygb
      expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to
      the abundance of Cygb, as well as this limbic structure being an important target
      in a number of neurodegenerative diseases. Using triple immunohistochemistry, it
      was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive
      neurons co-express Cygb and to a large extent, these neuron populations are
      distinct from the population of Cygb neurons co-expressing nNOS. Furthermore, it
      was shown that the majority of neurons expressing somastostatin and vasoactive
      intestinal peptide also co-express Cygb and nNOS. Detailed information regarding
      the neurochemical phenotype of Cygb neurons in the hippocampus can be a valuable
      tool in determining the function of Cygb in the brain.

PMID- 25054001
TI  - Effect of natural flavonoids, stilbenes and caffeic acid oligomers on protein
      glycation.
AB  - The aim of the present study was to identify the inhibitory activity of natural
      flavonoids, stilbenes and caffeic acid oligomers on protein glycation.
      Antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl radical
      scavenging activity. The production of 3-deoxyglucosone (3-DG) and advanced
      glycation end products (AGEs) by glycation reactions were determined by high
      performance liquid chromatography and fluorescence, respectively. Certain
      flavonoids, stilbenes and caffeic acid oligomers prevented AGE production and the
      IC50 values of the compounds were compared. These examined compounds are assumed
      to suppress AGE generation by inhibiting the increase in 3-DG production through
      a specific unknown mechanism in the early phase of the Maillard reaction, by
      inhibiting the generation of active oxygen in the later phase and by suppressing
      the progression of the reaction. Regular, daily consumption of these compounds in
      the form of a food or extract is expected to aid in the prevention or inhibition
      of non-enzymatic amino acid glycation in the living body, which is possibly
      associated with aging, diabetic complications, arteriosclerotic diseases and
      Alzheimer's disease, and they may also be effective agents in cosmetics promoting
      anti-aging.

PMID- 25054002
TI  - Triglyceride is strongly associated with nonalcoholic fatty liver disease among
      markers of hyperlipidemia and diabetes.
AB  - The aim of the present study was to reveal the metabolic disorders most commonly
      associated with nonalcoholic fatty liver disease (NAFLD). Triglyceride (TG), high
      density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL),
      blood glucose (BG) and hemoglobin A1c (HbA1c) were analyzed. NAFLD was diagnosed
      using abdominal ultrasound (US), and TG, HDL, LDL, BG and HbA1c were immediately
      collected on the same day and subjected to multivariate regression analysis.
      Stepwise analysis was performed to select the variables that were closely
      associated with NAFLD. The patients who were positive for the hepatitis B antigen
      and hepatitis C antibody were excluded from the study. Additionally, the patients
      who were prescribed prednisolone or methotrexate were excluded from the study as
      these agents may cause NAFLD or liver toxicity. The study included 168 and 125
      patients with and without NAFLD, respectively. TG, BG and HbA1c were strongly
      correlated with NAFLD. Among these parameters, TG was the strongest predictor of
      NAFLD (chi2=9.89, P=0.0017). TG was the parameter that was most strongly
      associated with NAFLD. In conclusion, elevated TG was a marker of NAFLD.

PMID- 25054003
TI  - Association of interleukin-6 (-174 G/C) polymorphism with the prostate cancer
      risk: A meta-analysis.
AB  - : The aim of the present study was to determine whether the interleukin-6 (IL-6)
      (-174 G/C) gene polymorphism correlates with prostate cancer. A meta-analysis
      based on former studies was conducted and the results suggest that there was no
      significant association between IL-6 (-174 G/C) polymorphism and the prostate
      cancer risk. However, a recent study published in January 2014 showed that the GG
      genotype may be associated with an increased risk of prostate cancer in Caucasian
      subjects, whereas the CC genotype was associated with an increased risk in the
      African-American subjects, which was inconsistent with former studies. Databases,
      including PubMed, Embase, Web of Science, the Cochrane Library, Chinese
      Biomedical Literature Database and Wanfang database, were searched between
      January 1994 and March 2014 to determine the eligible IL-6 (-174 G/C)
      polymorphism studies and the susceptibility of the prostate cancer risk. A total
      of 11 studies with 10,745 cases and 13,473 controls fulfilled the inclusion
      criteria subsequent to assessment by two investigators. The pooled odds ratio
      (OR) with 95% confidence interval (95% CI) was calculated to examine the
      associations, and subgroup analyses were performed according to the ethnicity.
      Overall, no significant association was found between the IL-6 (-174 G/C)
      polymorphism and prostate cancer risk, whereas the subgroup analysis suggested
      that the association between the IL-6 (-174 G/C) polymorphism and prostate cancer
      was slightly significant under the homozygote (CC vs. GG: OR, 3.43; 95% CI, 1.01
      11.71; P=0.049) and recessive models (CC vs. GG/GC: OR, 3.51; 95% CI, 1.04-11.82;
      P=0.042) in African-American patients. However, no significant association was
      found in the Caucasian, Asian or mixed populations under the five genetic models
      by stratifying studies for ethnicity. In conclusion, the present study suggested
      that there was no significant association between the IL-6 (-174 G/C)
      polymorphism and prostate cancer risk in Caucasian and Asian patients, whereas
      the CC genotype may be associated with an increased risk in the African-American
      patients.

PMID- 25054004
TI  - Cell culture of human gingival fibroblasts, oral cancer cells and mesothelioma
      cells with serum-free media, STK1 and STK2.
AB  - The majority of cells are cultured with Dulbecco's modified Eagle's medium (DMEM)
      or RPMI supplemented with fetal bovine serum (FBS), which contains numerous
      factors, including cytokines, nutrients and unknown growth factors. These factors
      may affect cell growth, apoptosis and differentiation. The serum-free medium,
      STK2, has been previously reported as suitable for the cell culture of human
      mesenchymal stem cells. However, how STK1 or STK2 affect the cell proliferation
      of normal and cancer cells remains unknown. The present study examined the growth
      of the human gingival fibroblast (HGF-1) cell-line and the HSC-3, CA9-22 and MSTO
      cancer cell-lines, cultured with STK1 and STK2. STK1 increased the cell
      proliferation of HGF-1 compared to DMEM by assessment with the 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H
      tetrazolium (MTS) assay, whereas STK1 and STK2 markedly inhibited the cell
      proliferation of HSC-3 and MSTO. The cell proliferation rate of CA9-22 cultured
      with STK1 or STK2 for 96 h was ~2-fold higher than the rate for 24 h culture. The
      shape of the HSC-3 cells was also found to have changed to round when cultured
      with STK2. These results indicate that STK1 increased the cell proliferation of
      HGF-1 compared to DMEM, whereas the proliferation of HSC-3 and MSTO was inhibited
      by STK1 and STK2. Thus, STK1 and STK2 had different affects on the cell growth of
      HGF-1, CA9-22, HSC-3 and MSTO.

PMID- 25054005
TI  - Rat injury model of docetaxel extravasation.
AB  - Docetaxel is a novel type of chemotherapy drug that actively treats a number of
      malignant tumors. The aim of the present study was to explore the severity and
      natural course of tissue damage induced by docetaxel extravasation and to confirm
      the vesicant potential of docetaxel. Rats were selected for the establishment of
      the ulcer model. Different volumes and concentrations were explored to induce the
      skin ulcer and to confirm the optimum rational injection model. The natural
      course of tissue injury and pathological changes produced by docetaxel
      extravasation were observed by comparing to vinorelbine extravasation. A 0.4 ml
      volume and a 6 mg/ml concentration were the optimum rational injection model for
      the induction of the skin ulcer. The docetaxel extravasation induced local tissue
      necrosis, followed by granuloma formation and hyperpigmentation or scar
      formation. The severity of the injury depended on the concentration of the
      extravasation used in the rat model. The injury occurred on the first day
      following extravasation and lasted 4-6 weeks. The damage from docetaxel was
      weaker than vinorelbine in association with the depth and extension of necrosis.
      In conclusion, docetaxel extravasation can induce tissue necrosis. However, the
      severity of necrosis was weaker than that of vinorelbine. Docetaxel has
      superficial vesicant properties.

PMID- 25054006
TI  - Promoter region methylation and loss of protein expression of PTEN and
      significance in cervical cancer.
AB  - The genetic basis underlying cervical tumorigenesis and progression are largely
      unknown. Phosphatase and tensin homologue (PTEN) is a tumor suppressor gene, and
      genetic changes of PTEN occurs in various types of cancer suggesting that the
      inactivation of PTEN may play an important role in the pathogenesis of a variety
      of human malignancies. In the present study, 102 cervical cancer specimens were
      examined for the expression of the PTEN gene and promoter methylation using
      methylation-specific-polymerase chain reaction and immunohistochemistry. The PTEN
      gene mutation was also assessed using PCR single-strand conformational
      polymorphism. We examined the correlation between PTEN expression and its
      associated methylation status and the clinical characteristics of cervical
      cancer. The results showed that there was one case of an A to G point mutation on
      exon 9 of the PTEN gene in the cervical cancer tissues. This mutation caused the
      change of aspartic acid to glycine, and the rate of mutation was 1%. The PTEN
      gene methylation rate of cervical cancer was 62% (63/102) and the rate was
      associated with the International Federation of Gynecology and Obstetrics stage,
      cell differentiation, tumor size and lymph node metastasis (P<0.05). The positive
      rate of PTEN expression was 49% (50/102) in cervical carcinoma and the PTEN
      expression between stage I-II and III-IV [60 (27/45) vs. 40% (23/57)] was
      statistically significant (P<0.01). The PTEN gene expression between the
      metastasis and no lymph node metastasis groups [26 (10/38) vs. 63% (40/64)] was
      significantly different (P<0.01). The PTEN gene promoter methylation and its
      protein expression had a significant correlation (P=0.042). These results suggest
      that hypermethylation can inactivate the transcription of PTEN and reduce its
      protein expression. Downregulated PTEN expression is involved in the
      pathogenesis, invasion and metastasis of cervical cancer, possibly by regulating
      the balance between apoptosis and proliferation. Therefore, the PTEN expression
      may be a good marker for the prognosis of cervical cancer.

PMID- 25054007
TI  - Comparison of in vitro and in vivo phototoxicity tests with S-(-)-10,11
      dihydroxyfarnesic acid methyl ester produced by Beauveria bassiana KACC46831.
AB  - Beauveria bassiana is a fungi that is well-known for demonstrating a resistance
      to environmental change. To confirm whether S-(-)-10,11-dihydroxyfarnesic acid
      methyl ester (DHFAME) produced by Beauveria bassiana KACC46831 causes
      phototoxicity when used for cosmetic purposes due to its anti-tyrosinase
      activity, we conducted in vitro and in vivo phototoxicity tests. There were no
      significant changes or damage observed in the compound-treated group with regards
      to skin phototoxicity, while 8-methoxypsoralen, which served as a positive
      control, induced toxic effects. The in vitro 3T3 neutral red uptake assay, an
      alternative assessment, was used for further confirmation of the phototoxicity.
      The results showed that DHFAME did not exhibit phototoxicity at the designated
      concentrations, with or without UV irradiation in the 3T3 cells. These results
      indicated that the methyl ester produced by Beauveria bassiana KACC46831 does not
      induce phototoxicity in the skin. Therefore, the results of the present study
      indicate that DHFAME shows potential for use as a cosmetic ingredient that does
      not cause skin phototoxicity.

PMID- 25054008
TI  - Microarray comparison of the gene expression profiles in the adult vs. embryonic
      day 14 rat liver.
AB  - The aim of the present study was to identify the differentially-expressed genes
      of embryonic day 14 (ED 14) rat liver in comparison to adult rat liver, which may
      provide specific information for the investigation of the hepatogenesis
      mechanism. The gene expression profiles of ED 14 and adult rat livers were
      investigated using microarray analysis (the Illumina RatRef-12 Expression
      BeadChip). Quantitative polymerase chain reaction (qPCR) analyses were conducted
      to confirm the gene expression. There were 787 genes upregulated in the embryonic
      liver. Based on the gene ontology classification system, which was analyzed by
      the database for annotation, visualization and integrated discovery software, a
      number of the upregulated genes were categorized into the distinct and
      differentially-expressed functional groups, including metabolism pathway, cell
      cycle, transcription, signal transduction, purine metabolism, cell structure,
      transportation and apoptosis. qPCR analyses confirmed the gene expression. Eleven
      upregulated genes were found in the ED 14 rat liver, which may provide specific
      information for the understanding of the molecular mechanisms that control
      hepatogenesis. These overexpressed genes are potential markers for identifying
      hepatic progenitor cells.

PMID- 25054009
TI  - Anti-inflammatory effects of ozonated water in an experimental mouse model.
AB  - Previous studies have suggested that ozonated water is safe and possesses
      antibacterial effects for treatment of experimental peritonitis rats. In this
      study, we evaluated the anti-inflammatory effects of ozonated water that was
      intraperitoneally injected into an experimental inflammatory mouse model. The
      concentrations of dissolved ozone decreased constantly and lineally, while the
      half-life of dissolved ozone was 36.8+/-2.7 min (27 degrees C). The 10-ppm
      ozonated water was injected intraperitoneally into mice with lipopolysaccharide
      (LPS)-induced acute inflammation. The results showed that the intraperitoneal
      injection of ozonated water decreased the levels of tumor necrosis factor-alpha
      (TNF-alpha) and increased the activity of superoxide dismutase (SOD). The results
      suggest that ozonated water has anti-inflammatory properties and is a potential
      therapeutic option for acute inflammation.

PMID- 25054010
TI  - Antioxidant activities and polyphenol content of Morus alba leaf extracts
      collected from varying regions.
AB  - Morus alba leaf (MAL), also known as Mori folium when used as a herbal medicine,
      has traditionally been used in Chinese medicine to treat diabetes, protect the
      liver and lower blood pressure. In the present study, MAL was collected from
      various regions in Korea and the antioxidant activity, total polyphenol contents
      and main flavonoid contents was investigated. MAL were collected from various
      areas in Korea and extracted with methanol. The total polyphenol contents were
      evaluated based on the Folin-Ciocalteu method using a spectrophotometer. The
      antioxidant activities were determined by a 2,2-diphenyl-1-picrylhydrazyl radical
      scavenging assay method. The identification and quantification of three main
      polyphenol constituents was performed using high-performance liquid
      chromatography/diode array detection analysis. The total polyphenol contents of
      the MAL extracts varied between 23.2 and 55.4 mg gallic acid equivalent/g. The
      radical scavenging activity (SC50) of the MAL extracts ranged between 584 and 139
      MUg/ml. Three flavonol compounds (rutin, isoquercitrin and astragalin) were
      identified as main polyphenol constituents. These contents varied from 0.68-12.7,
      0.69-9.86 and 0.05-3.55 mg/g, respectively. The average of the total was 9.52
      mg/g, which was similar to that of commercial MAL extracts (10.58 mg/g). Among
      the three flavonol compounds, isoquercitrin showed the highest content (5.68
      mg/g) followed by rutin (3.1 mg/g) and astragalin (2.4 mg/g). In the present
      study, the radical scavenging activity, polyphenol content and flavonol content
      of MAL were significantly different according to growing area. These three
      flavonol compounds were identified as main constituents of MAL in this study, and
      are known to have various biological activities, as well as strong antioxidant
      activities. Therefore, the sum of these three flavonol compounds was indicated as
      a good marker for the quality control of Mori folium.

PMID- 25054011
TI  - Fat mass and obesity-associated gene rs11642015 polymorphism is significantly
      associated with prediabetes and type 2 diabetes subsequent to adjustment for body
      mass index.
AB  - The association of the fat mass and obesity-associated gene (FTO) rs11642015
      polymorphism with prediabetes, type 2 diabetes and obesity in certain populations
      has not been previously reported. A population-based study was conducted that
      included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main
      outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary
      logistic regression was performed to estimate the association of FTO rs11642015
      with the risk of prediabetes, type 2 diabetes and obesity following adjustment
      for the corresponding confounders. A meta-analysis was also conducted to evaluate
      the association between FTO rs11642015 and obesity. FTO rs11642015 was
      significantly associated with prediabetes in the whole sample under the additive
      model [odds ratio (OR), 1.50; 95% confidence interval (CI), 1.17-1.93; P=0.002],
      particularly in females. The polymorphism remained consistently significant
      following adjustment for age and body mass index (BMI), showing an increased
      prediabetes risk with an additive effect (OR, 1.55; 95% CI, 1.19-2.01; P=0.001).
      In addition, a significant association was found for rs11642015 with prediabetes
      and type 2 diabetes under the dominant model. However, under the stringent
      Bonferroni's correction there was no evidence of positive associations for FTO
      rs11642015 with obesity in the whole sample, females or males. Findings of the
      meta-analysis showed that FTO rs11642015 was not predisposed to obesity. In
      conclusion, the T allele of FTO rs11642015 is positively associated with an
      increased risk of prediabetes, even after adjustment for age and BMI,
      particularly in females. Subjects carrying the CT + TT genotype are predisposed
      to prediabetes and type 2 diabetes. Therefore, results of the population-based
      study and follow-up meta-analysis suggested that FTO rs11642015 is not
      significantly associated with susceptibility to obesity.

PMID- 25054012
TI  - Effects of lycium barbarum polysaccharides on neuropeptide Y and heat-shock
      protein 70 expression in rats exposed to heat.
AB  - The purpose of the present study was to investigate the effects of high ambient
      temperature on the neuropeptide Y (NPY) mRNA level in the hypothalamus, the
      plasma concentration of corticotropin-releasing hormone (CRH), cortisol (Cor),
      heat-shock protein 70 (HSP70) and epinephrine (EPI), and the intervention of
      lycium barbarum polysaccharides (LBPs) in rats. Compared to the control (CN)
      group, the plasma levels of CRH, Cor, HSP70 and EPI were markedly increased, and
      the level of NPY mRNA was downregulated in the high ambient temperature (HT)
      group. By contrast, rats in the HT + LBP (HTL) group had: i) a significantly
      enhanced expression of HSP70 compared to the HT and CN groups; ii) clearly
      increased plasma levels of CRH, Cor and EPI compared to the CN group; and iii) a
      markedly upregulated expression of NPY mRNA compared to the HT group. Thus, the
      results showed that high-temperature environments may damage the body, and LBPs
      have a potentially protective function by increasing the expression of HSP70 and
      NPY.

PMID- 25054013
TI  - Comparative analysis of serum proteomes: Identification of proteins associated
      with sciatica due to lumbar intervertebral disc herniation.
AB  - Lumbar intervertebral disc herniation (LDH) is one of the most common orthopedic
      conditions that can cause lower back pain and sciatica. However, the pathogenesis
      of LDH is poorly understood. The aim of the present study was to use proteomic
      analysis of blood samples to establish whether there are serum proteins
      associated with LDH, which may be useful in elucidating LDH pathogenesis. The
      ultimate aim was to develop a simple technique for the diagnosis of LDH based on
      the blood samples of patients with sciatica. The study used comparative analysis
      of serum proteomes associated with sciatica due to LDH. A total of 30 LDH
      patients with sciatica, receiving treatment between August and December 2007,
      were selected as the experimental group (or LDH group). A total of 2 ml of blood
      was obtained from each of the 30 patients in the LDH group and from 30 healthy
      volunteers, who constituted the control group. Two-dimensional electrophoresis of
      the blood samples was conducted, distinct protein spots were identified by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and
      proteins associated with LDH were detected. An enzyme-linked immunosorbent assay
      (ELISA) was developed to screen for the LDH proteins and was tested on the sera
      of a second test and control group that included 10 patients with LDH and 10
      healthy subjects, respectively. Based on signal intensity, the expression levels
      of 6 proteins on the dielectrophoretogram were found to be significantly
      associated with LDH. The identities of the LDH proteins were upregulated
      apolipoprotein-L1 (APO-L1) and two types of serum albumin precursors, and
      downregulated apolipoprotein M (APO-M), tetranectin (TN) and immunoglobulin light
      chain (IGL). Further ELISA experiments confirmed that there were increased serum
      levels of 4 out of the 6 proteins in patients with sciatica due to LDH, which was
      statistically different compared to the healthy subjects. In conclusion, these
      results suggest that serum APO-L1, TN, APO-M and IGL may serve as LDH biomarkers.

PMID- 25054014
TI  - Methylenetetrahydrofolate reductase C677T gene polymorphism and essential
      hypertension: A meta-analysis of 10,415 subjects.
AB  - The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism has been
      suggested to be associated with the risk of essential hypertension (EH), however,
      results remain inconclusive. To investigate this association, the present meta
      analysis of 27 studies including 5,418 cases and 4,997 controls was performed.
      The pooled odds ratio (OR) and its corresponding 95% confidence interval were
      calculated using the random-effects model. A significant association between the
      MTHFR C677T gene polymorphism and EH was found under the allelic (OR, 1.32; 95%
      CI, 1.20-1.45; P=0.000), dominant (OR, 1.39; 95% CI, 1.25-1.55; P=0.000),
      recessive (OR, 1.38; 95% CI, 1.18-1.62; P=0.000), homozygote (OR, 1.59; 95% CI,
      1.32-1.92; P=0.000), and heterozygote (OR, 1.32; 95% CI, 1.20-1.45; P=0.000)
      genetic models. A strong association was also revealed in subgroups, including
      Asian, Caucasian and Chinese. The Japanese subgroup did not show any significant
      association under all models. Meta-regression analyses suggested that the study
      design was a potential source of heterogeneity, whereas the subgroup analysis
      additionally indicated that the population origin may also be an explanation.
      Another subgroup analysis revealed that hospital-based studies have a stronger
      association than population-based studies, however, the former suffered a greater
      heterogeneity. Funnel plot and Egger's test manifested no evidence of publication
      bias. In conclusion, the present study supports the evidence for the association
      between the MTHFR C677T gene polymorphism and EH in the whole population, as well
      as in subgroups, such as Asian, Caucasian and Chinese. The carriers of the 677T
      allele are susceptible to EH.

PMID- 25054015
TI  - Catabolite control protein A is an important regulator of metabolism in
      Streptococcus suis type 2.
AB  - Streptococcus suis (S. suis) type 2 is an extremely important Gram-positive
      bacterial pathogen that can cause human or swine endocarditis, meningitis,
      bronchopneumonia, arthritis and sepsis. Catabolite control protein A (CcpA) is a
      major transcriptional regulator in S. suis type 2 that functions in catabolite
      control, specifically during growth on glucose or galactose. The regulation of
      central metabolism can affect the virulence of bacteria. In the present study, a
      metabolomics approach was used along with principal components analysis (PCA) and
      partial least-squares-discriminant analysis (PLS-DA) models and 37 metabolites
      were found that differed substantially between native S. suis and a mutant
      lacking CcpA. These results showed that CcpA is an important protein in S. suis
      type 2 for studying bacterial protein function.

PMID- 25054016
TI  - Association of NQO1 and TNF polymorphisms with Parkinson's disease: A meta
      analysis of 15 genetic association studies.
AB  - Parkinson's disease (PD) is a neurodegenerative movement d'isorder that affects
      ~2% of the population aged >=65 years. NAD(P)H-quinone oxidoreductase 1 (NQO1)
      and tumor necrosis factor-alpha (TNF-alpha) are two important factors in the
      generation of oxidative stress in PD. The aim of the present study was to assess
      the association of NQO1 and tumor necrosis factor (TNF) polymorphisms with PD. A
      meta-analysis was performed that included data from 15 studies comprising 2,858
      patients and 2,907 healthy controls. The results showed that TNF-1031 (rs1799964)
      was significantly associated with PD in the recessive [P=0.0005; odds ratio (OR),
      3.19; 95% confidence interval (CI), 1.66-6.13] and additive models (P=0.0006; OR,
      3.15; 95% CI, 1.63-3.51). However, there was no significant association in NQO1
      C609T (rs1800566) and TNF-308 (rs1800629) with PD. To the best of our knowledge,
      the present study is the first meta-analysis of NQO1 and TNF polymorphisms with
      PD demonstrating that TNF-1031 polymorphism may be a risk factor for PD under
      either the recessive or additive models. However, the meta-analyses did not
      support the involvement of NQO1 C609T and TNF-308 in the risk of PD.

PMID- 25054017
TI  - Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk.
AB  - Murine double minute 2 (MDM2) is a negative regulator of p53. A single-nucleotide
      polymorphism (SNP) (rs2279744: c.309T>G) in the promoter region of the MDM2 gene
      has been shown to result in higher levels of MDM2 RNA and protein. Regarding the
      contribution of c.309T>G in the MDM2 gene to the lung cancer risk, previous
      studies are conflicting. In order to evaluate the association between c.309T>G
      and the lung cancer risk, a case-control study was performed. The MDM2 genotypes
      were determined in 762 lung cancer patients and in 700 cancer-free control
      subjects using the Smart Amplification Process. Statistical adjustment was
      performed for gender, age and pack-years of smoking. The distributions of
      c.309T>G (T/T, T/G, G/G) were 20.1, 49.7, 30.2% in the case group and 21.7, 47.9,
      30.4% in the healthy-control group. There were no overall associations between
      the MDM2 genotypes and the risk of lung cancer [T/G genotype: Adjusted odds ratio
      (AOR), 1.30; 95% confidence interval (CI), 0.88-1.93; and G/G genotype: AOR,
      1.18; 95% CI, 0.78-1.80]. The subgroup analysis of gender, histology, smoking
      status and epidermal growth factor receptor mutation status also indicated that
      there was no association with lung cancer. Additionally, the genotypes did not
      have an effect on the age at the time of diagnosis of lung cancer (P=0.25). In
      conclusion, the G allele frequency in the lung cancer cases was 0.551, which was
      similar to other studies. The results of the present study suggest that the
      c.309T>G is not significantly associated with lung cancer.

PMID- 25054018
TI  - Expression of vimentin filaments in canine malignant mammary gland tumors: A
      simulation of clinicopathological features of human breast cancer.
AB  - Canine malignant mammary gland tumors (CMMGTs) are the most common malignancies
      observed in females. Several biological similarities have been reported between
      CMMGTs and human breast cancer (HBC). The present study aimed to assess the
      correlation of vimentin filaments overexpression, as part of the process of
      epithelial-mesenchymal transition (EMT) and the clinicopathological
      characteristics in CMMGTs. The clinicopathological characteristics of 42 CMMGTs
      were collected. Paraffin-embedded blocks underwent immunohistochemistry staining,
      which was performed using vimentin (to assess the evolution of the EMT process),
      Ki-67 (for evaluation of tumor proliferation) and cluster of differentiation 34
      (CD34) (for evaluation of angiogenesis) antibodies. The tumor stage, grade,
      vascular invasion, margin status, rate of expression of the vimentin filaments,
      microvessel density-CD34 and proliferation rate data were obtained. Finally, the
      association between the expression of the vimentin filaments and those parameters
      was resolved statistically. A significant association was shown between the
      overexpression of the vimentin filaments and tumor size (r=0.71, P=0.03), tumor
      grade (r=0.80, P=0.021), angiogenesis (r=0.57, P=0.043), proliferation
      coefficient (r=0.06, P=0.001) and vascular invasion (r=0.76, P=0.043). Vimentin
      overexpression did not statistically correlate with the tumor stage or the margin
      status. Similar to the findings of the present study, certain recent studies have
      indicated that vimentin filament expression in HBC and CMMGTs is associated with
      the severity of cancer. Thus, spontaneous canine mammary tumor models appear to
      be an appropriate animal model for breast cancer research, and the results of the
      present study could aid to reinforce the association.

PMID- 25054019
TI  - Meta-analyses of 10 polymorphisms associated with the risk of schizophrenia.
AB  - Schizophrenia (SCZ) is a severe complex psychiatric disorder that generates
      problems for the associated family and society and causes disability with regards
      to work for patients. The aim of the present study was to assess the contribution
      of 10 genetic polymorphisms to SCZ susceptibility. Meta-analyses were conducted
      using the data without a limitation for time or language. A total of 27 studies
      with 7 genes and 10 polymorphisms were selected for the meta-analyses. Two
      polymorphisms were found to be significantly associated with SCZ. SNAP25
      rs3746544 was shown to increase the SCZ risk by 18% [P=0.01; odds ratio (OR),
      1.18; 95% confidence interval (CI), 1.05-1.34] and GRIK3 rs6691840 was found to
      increase the risk by 30% (P=0.008; OR, 1.30; 95% CI, 1.07-1.58). Significant
      results were found under the dominant (P=0.001; OR, 1.36; 95% CI, 1.13-1.65) and
      additive (P=0.02; OR, 1.45; 95% CI, 1.06-1.98) model for the SNAP25 rs3746544
      polymorphism and under the additive model for the GRIK3 rs6691840 polymorphism
      (P=0.03; OR, 1.73; 95% CI, 1.04-2.85). There were no significant results observed
      for the other eight polymorphisms, which were CCKAR rs1800857, CHRNA7 rs904952,
      CHRNA7 rs6494223, CHRNA7 rs2337506, DBH Ins>Del, FEZ1 rs559668, FEZ1 rs597570 and
      GCLM rs2301022. In conclusion, the present meta-analyses indicated that the
      SNAP25 rs3746544 and GRIK3 rs6691840 polymorphisms were risk factors of SCZ,
      which may provide valuable information for the clinical diagnosis of SCZ.

PMID- 25054020
TI  - Comparison of the serum fibrin-fibrinogen degradation products with cytokeratin
      19 fragment as biomarkers in patients with lung cancer.
AB  - Lung cancer is one of the main causes of cancer-related mortality. The
      identification of early diagnostic biomarkers improved outcomes for lung cancer
      patients. Serum fibrin-fibrinogen degradation products (FDP) levels are elevated
      in numerous malignancies due to hemostatic alterations. The serum FDP levels were
      compared to the levels of cytokeratin 19 fragment antigen (CYFRA 21-1), another
      well-established biomarker. The serum samples from 193 lung cancer patients, 84
      healthy controls and 106 patients with benign respiratory diseases were obtained.
      The serum FDP level was measured using the DR-70 immunoassay and the CYFRA 21-1
      level was measured by electrochemiluminescence using the Roche Analytics E170.
      Receiver operating characteristics curves were used to assess the predictive
      sensitivity and specificity. The mean serum FDP level in lung cancer patients
      (35.01+/-229.02 MUg/ml) was significantly higher compared to the 190 non
      cancerous subjects (0.60+/-0.75 MUg/ml; P=0.039). The mean serum CYFRA 21-1 level
      in lung cancer patients (4.50+/-6.67 ng/ml) was also significantly higher
      compared to the non-cancerous subjects (1.40+/-0.83 ng/ml; P<0.05). FDP exhibited
      clinical sensitivity and specificity of 86 and 75%, respectively, at an optimal
      cut-off at 0.67 MUg/ml. CYFRA 21-1 exhibited clinical sensitivity and specificity
      of 77 and 74%, respectively, at a cut-off of 1.65 ng/ml. The serum FDP area under
      the curve (0.87) was slightly higher compared to CYFRA 21-1 (0.83). Therefore, it
      is apparent that serum FDP is comparable to CYFRA 21-1 as a lung cancer biomarker
      and can be used for clinical practice.

PMID- 25054021
TI  - Investigation of toxin gene diversity and antimicrobial resistance of Clostridium
      difficile strains.
AB  - The incidence of Clostridium difficile infection (CDI) has been previously
      reported in a number of studies. However, data collected from the Chinese
      population is limited. In the present study, the diversity of the toxin genes,
      tcdA and tcdB, of 57 Clostridium difficile (C. difficile) isolates from a Chinese
      population were investigated by polymerase chain reaction (PCR) (38 A+B+, 14 A-B+
      and 5 A-B-). Quantitative PCR was used to check the expression of these two genes
      and it was found that the genes were not expressed by all the strains. The
      absence of tcdA or tcdB expression in certain strains could be due to the lower
      expression of tcdD and the higher expression of tcdC, which are positive and
      negative regulators for these two toxin genes, respectively. In addition, the
      antimicrobial susceptibilities of 57 isolates were investigated. Therefore, these
      data would aid in the future prevention of CDI outbreaks and improve the
      understanding of the infection.

PMID- 25054022
TI  - Association of CYP11B2 polymorphisms with metabolic syndrome patients.
AB  - Aldosterone synthase is a key enzyme in aldosterone production. Polymorphisms of
      the aldosterone synthase gene, CYP11B2, have been suggested to be involved in the
      pathogenesis of diabetes mellitus (DM), hypertension and cardiovascular diseases.
      In the light of these findings, we hypothesized that CYP11B2 genetic
      polymorphisms play a role in metabolic syndrome (MetS). Therefore, we
      investigated the associations of three CYP11B2 polymorphisms [-344T>C, K173R and
      intron 2 conversion (IC)] with Korean MetS patients. In total, 640 subjects
      comprising 320 cases and 320 control individuals) were included in the present
      study. Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) techniques were used to assess CYP11B2 polymorphisms. The CYP11B2 -344T>C,
      K173R and IC polymorphisms did not exhibit a significant difference in the
      genotype and allele frequencies between the MetS and control groups. However, the
      -344T>C polymorphism in males and haplotypes comprising the three polymorphisms
      were associated with susceptibility to MetS. Thus, the pattern of haplotype
      associations was gender-specific. Based on these results, the -344T>C
      polymorphism in males and haplotypes of the CYP11B2 gene potentially affect MetS
      susceptibility. These findings remain to be confirmed in various ethnic
      populations with a larger sample size.

PMID- 25054023
TI  - Protective effect of trehalose-loaded liposomes against UVB-induced photodamage
      in human keratinocytes.
AB  - Trehalose, a naturally occurring non-reducing disaccharide, is known to act as a
      major protein stabilizer that can reduce ultraviolet B (UVB)-induced corneal
      damage when topically applied to the eye. However, due to the low skin
      permeability of trehalose, which makes the development of topical formulations
      difficult, its use as a skin photoprotective agent has been limited. Previous
      findings demonstrated that liposomes may significantly improve the intracellular
      delivery of trehalose. Therefore, the present study aimed to assess the
      protective effects of trehalose-loaded liposomes against UVB-induced photodamage
      using the immortalized human keratinocyte cell line, HaCaT. The effects were also
      compared to those of the common skin photoprotective compounds, including L
      carnosine, L-(+)-ergothioneine, L-ascorbic acid and DL-alpha-tocopherol. The
      levels of cyclobutane pyrimidine dimers, 8-hydroxy-2'-deoxyguanosine and protein
      carbonylation in HaCaT cells were used as biological markers of UVB-induced
      damage. Compared to other compounds, trehalose-loaded liposomes showed the
      highest efficacy in reducing the levels of the three markers following UVB
      irradiation of HaCaT cells (all P<0.001 when compared to each of the four other
      photoprotective compounds). Therefore, these findings indicate that there may be
      a clinical application for trehalose-loaded liposomes, and further studies should
      be performed to assess the potential usefulness in skin photoprotection and the
      prevention of non-melanoma skin cancer.

PMID- 25054024
TI  - Inhibition of COX-2 and PGE2 in LPS-stimulated RAW264.7 cells by lonimacranthoide
      VI, a chlorogenic acid ester saponin.
AB  - Lonimacranthoide VI, first isolated from the flower buds of Lonicera
      macranthoides in our previous study, is a rare chlorogenic acid ester acylated at
      C-23 of hederagenin. In the present study, the anti-inflammatory effects of
      lonimacranthoide VI were studied. Lipopolysaccharides (LPS) induced an
      inflammatory response through the production of prostaglandin E2 (PGE2), and
      these levels were reduced when lonimacranthoide VI was pre-administered.
      Additionally, the mechanism of the anti-inflammatory effects of lonimacranthoide
      VI was investigated by measuring cyclooxygenase (COX) activity and mRNA
      expression. The results showed that lonimacranthoide VI inhibited mRNA expression
      and in vitro activity of COX-2 in a dose-dependent manner, whereas only the
      higher lonimacranthoide VI concentration possibly reduced COX-1 expression and in
      vitro activity. Taken together, these results indicate that lonimacranthoide VI
      is an important anti-inflammatory constituent of Lonicera macranthoides and that
      the anti-inflammatory effect is attributed to the inhibition of PGE2 production
      through COX activity and mRNA expression.

PMID- 25054025
TI  - Transthyretin as a potential biomarker for the differential diagnosis between
      lung cancer and lung infection.
AB  - Satisfactory biomarkers for screening and early diagnosis of lung cancer remain
      scarce and require further investigation. The aim of the present study was to
      examine the changes of the biochemical and protein composition in the serum and
      pleural effusion from lung cancer and lung infection (bacterial pneumonia)
      patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia
      and 42 healthy controls were enrolled in the study. The serum levels of
      cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients
      were higher than that of the lung infection patients (P<0.05). The levels of TTR
      were higher, whereas the activity of adenosine deaminase (ADA) was lower in the
      pleural effusion from the lung cancer patients compared to the lung infection
      patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung
      cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and
      Cysgly-TTR were observed in the serum of the lung cancer and lung infection
      patients. A significant increase was found in the proportion of Cysgly-TTR in the
      pleural effusion from the patients with lung cancer. The data indicated that a
      combination of pleural effusion/serum TTR ratios and modified TTR may be
      beneficial for the differential diagnosis between lung cancer and lung infection.

PMID- 25054027
TI  - Advances in intravesical therapy for the treatment of non-muscle invasive bladder
      cancer (Review).
AB  - The knowledge of tumor biology and the biomechanical properties of the urothelium
      have led to significant advances in the development of intravesical therapy for
      the treatment of non-muscle invasive bladder cancer (NMIBC). Targeted therapy
      improves the efficacy and decreases the side effects of antineoplastic agents.
      Nanoparticles that target antitumor agents to the urothelial cells have allowed
      for improved delivery of these agents to tumor cells. Gene therapy is another
      strategy that has allowed for a targeted induction of an antitumor response.
      Finally, engineering of the bacillus Calmette-Guerin (BCG) vaccine aimed to
      minimize the potential side effects associated with this treatment. These novel
      approaches hold promise for decreasing the rate of progression and recurrence of
      NMIBC.

PMID- 25054026
TI  - Candidate biomarkers for cervical cancer treatment: Potential for clinical
      practice (Review).
AB  - Cervical cancer ranks high among the causes of female cancer mortalities and is
      an important disease in developing and developed countries. Current diagnosis of
      cervical cancer depends on colposcopy, pathological diagnosis and preoperative
      diagnosis using methods, including magnetic resonance imaging and computed
      tomography. Advanced cervical cancer has a poor prognosis. The tumor marker
      squamous cell carcinoma is conventionally used for screening, but recent studies
      have revealed the mechanisms of carcinogenesis and the factors associated with a
      poor prognosis in cervical cancer. These include epigenetic biomarkers, with the
      methylation level of the checkpoint with forkhead and ring finger gene being
      potentially useful for predicting the malignancy of cervical cancer and
      sensitivity to treatment with paclitaxel. The extent of methylation of the Werner
      DNA helicase gene is also useful for determining sensitivity to an anticancer
      agent, CPT-11. In addition to epigenetic changes, the expression levels of
      hypoxia-inducible factor 1alpha subunit, epidermal growth factor receptor and
      cyclooxygenase-2 have been reported as possible biomarkers in cervical cancer.
      Novel prognostic factors, including angiogenic factors, fragile histidine triad,
      thymidylate synthase, glucose-related protein 58 and mucin antigens, have also
      been described, and hemoglobin and platelets may also be significant prognostic
      biomarkers. Utilization of these biomarkers may facilitate personalized treatment
      and improved outcomes in cervical cancer.

PMID- 25054028
TI  - Autophagy: A potential target for thyroid cancer therapy (Review).
AB  - The sharply increasing incidence of thyroid cancer has attracted considerable
      attention over the last few years. The combination of surgery, radioiodine
      ablation and thyroid-stimulating hormone suppression is usually efficient for the
      majority of thyroid tumors. However, advanced thyroid cancer that is recurrent,
      metastatic and 131I-refractory, or medullary thyroid cancer, pose a therapeutic
      challenge. Autophagy is a process that metabolizes damaged cytoplasmic organelles
      and long-lived proteins in order to recycle cellular materials and maintain
      homeostasis. It has been confirmed that autophagy plays a dual role during cancer
      development, progression and treatment, mainly depending on the type and stage of
      the tumor. Autophagy modulation has become a potential therapeutic target for
      diverse diseases. The mechanism of thyroid tumorigenesis and cancer progression
      was largely demonstrated to be correlated with the dysregulation of the
      Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated
      kinase and the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin
      pathways, as well as with abnormal epigenetic modifications. Those mechanisms are
      associated with autophagy regulation and may be beneficial for the treatment of
      advanced thyroid cancer. However, the number of available studies on the role of
      autophagy in thyroid cancer development, progression and treatment outcome, is
      currently limited. The aim of this review was to elaborate on the relevant
      knowledge and future prospectives of autophagy in the treatment of thyroid
      cancer.

PMID- 25054029
TI  - Parametric contrast-enhanced ultrasound as an early predictor of radiation-based
      therapeutic response for lymph node metastases of nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a common type of cancer in South East Asia with
      peculiar epidemiology, pathology, clinical behavior and response to treatment
      characteristics. To the best of our knowledge, this is the first study to
      investigate the use of a contrast-enhanced ultrasound (CEUS) as a predictor for
      the therapeutic response in lymph node metastases of NPC patients treated with
      radiation-based therapy. Sixty-seven NPC patients with lymph node metastases
      underwent the lymph nodes CEUS examination twice; pre- and in-treatment (at the
      5th fraction radiotherapy), respectively. The CEUS parameters were acquired
      through Qontrast_4.0 software and mainly included peak intensity (PI) and time to
      peak (TTP). The response assessment at the lymph nodes revealed a complete
      response (CR) in 48 patients and partial response (PR) in 19 patients. There was
      a significant difference in pre-treatment PI (PIpre) between the patients who
      showed CR or PR, but the predicted sensitivity and specificity of PIpre was low.
      The mean in-treatment PI (PIin) value of the lymph nodes that achieved a CR was
      34.24+/-3.78%, which was significantly higher than the PIin value for PR, 25.62+/
      2.30% (P<0.001). Furthermore, the PIratio, a PI-quotient, was calculated by
      dividing the PIin by the corresponding PIpre. The higher PIratio was also
      observed in CR lymph nodes (0.81+/-0.01 vs. 0.66+/-0.01; P=0.001), and the mean
      change in PI (PIDelta; PIDelta = PIpre-PIin) was smaller in the patients with CR
      nodes compared to the patients with PR nodes (7.79+/-3.28 vs. 13.77+/-1.90%;
      P=0.000). No difference was observed in TTPpre or TTPin between the CR or PR
      lymph nodes patients. A receiver operating characteristic curve was constructed
      to assess the accuracy of the parameters for the prediction of the therapeutic
      responses. The sensitivity and specificity of PIin in predicting the therapeutic
      response was 94.3 and 88.2%, and the corresponding figures of the PIratio were
      92.5 and 83.8%, respectively. The CEUS parameters during the early course of
      radiation-based therapy, PIin and PIratio, are associated with the therapeutic
      response of NPC lymph node metastases, with a high predicted sensitivity and
      specificity, thus yielding the conceivable predictors with the potential to
      individualize treatment.

PMID- 25054030
TI  - Observational study of patients with gastroenteropancreatic and bronchial
      neuroendocrine tumors in Argentina: Results from the large database of a
      multidisciplinary group clinical multicenter study.
AB  - Neuroendocrine tumors (NET) include a spectrum of malignancies arising from
      neuroendocrine cells throughout the body. The objective of this clinical
      investigation of retrospectively and prospectively collected data was to describe
      the prevalence, demographic data, clinical symptoms and methods of diagnosis of
      NET and the treatment and long-term follow-up of patients with NET. Data were
      provided by the participating centers and assessed for consistency by internal
      reviewers. All the cases were centrally evaluated (when necessary) by the
      pathologists in our group. The tissue samples were reviewed by hematoxylin and
      eosin and immunohistochemical staining techniques to confirm the diagnosis of
      NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP
      NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically
      defined according to the World Health Organization (WHO) and European
      Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP
      NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal
      bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non
      functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%)
      and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0%
      atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis
      at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel
      (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%),
      esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological
      subtypes based on the WHO classification were well-differentiated NET (20.1%),
      well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated
      neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent
      surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year
      survival rates were 65.1% (95% confidence interval, 58.0-71.4%) in GEP-NET and
      100.0% in typical carcinoid of the lung. This observational, non-interventional,
      longitudinal study aimed to accumulate relevant information regarding the
      epidemiology, clinical presentation and current practices in the treatment of NET
      patients in Argentina, providing insight into regional differences and patterns
      of care in this heterogeneous disease.

PMID- 25054031
TI  - Prognostic value of peripheral and local forkhead box P3+ regulatory T cells in
      patients with non-small-cell lung cancer.
AB  - Several types of immunosuppressive mechanisms in cancer patients have been
      reported to date. Regulatory T cells (Tregs), which express the master control
      transcription factor forkhead box P3 (FoxP3), are considered to play a major role
      in hampering antitumor immune response. However, the clinical significance of
      Tregs in patients with lung cancer has not been fully elucidated. The aim of this
      study was to investigate the clinical significance of Tregs in the peripheral
      blood and in resected cancer tissue specimens. We analyzed peripheral blood
      mononuclear cells (PBMCs) collected prior to surgery and resected specimens
      obtained from 67 patients with non-small-cell lung cancer (NSCLC). Peripheral
      Tregs (pTregs) were detected as CD4+ and FoxP3+ cells by flow cytometry.
      Immunohistochemical staining for CD4, CD8 and FoxP3 expression was also performed
      quantitatively by analyzing three randomly selected fields from central regions
      (cCD4, cCD8 and cFoxP3) and interstitial regions of the tumors (iCD4, iCD8 and
      iFoxP3). The associations between the expression frequencies in selected cells
      and clinicopathological parameters were statistically analyzed. The frequency of
      pTregs was found to be significantly higher in patients with pleural invasion
      (P=0.0049), vessel invasion (P=0.0009), lymphatic vessel invasion (P=0.0053) and
      recurrent disease (P=0.0112). Patients with T1 exhibited a significantly higher
      frequency of cCD4 (P=0.0199) and cCD8 (P=0.0058), although cFoxP3 expression was
      not significant (P=0.0935). Patients with low levels of cFoxP3/iFoxP3 exhibited a
      significantly higher frequency of pTregs (P=0.0338) and patients with a high
      frequency of pTregs exhibited significantly poorer recurrence-free survival
      (P=0.0071). The multivariate analysis identified pTreg frequency as an
      independent prognostic factor (P=0.0458). Although the pathological analysis
      remains controversial, the frequency of pTregs in NSCLC patients may be a useful
      prognostic biomarker.

PMID- 25054032
TI  - Thalidomide plus chemotherapy exhibit enhanced efficacy in the clinical treatment
      of T-cell non-Hodgkin's lymphoma: A prospective study of 46 cases.
AB  - The treatment of T-cell non-Hodgkin's lymphoma (T-NHL) remains challenging. There
      is currently no standard regimen for the treatment of T-NHL in the first- or
      second-line setting. Thalidomide was previously shown to exert antitumor effects
      through inhibiting angiogenesis, promoting apoptosis and immunomodulatory
      activity. However, all the previous studies on the treatment of lymphoma with
      thalidomide included patient samples of limited size. In the present study, 46
      cases of eligible T-NHL patients were randomized into i) the control group
      (conventional combined chemotherapy, n=22) and ii) the thalidomide group
      (thalidomide plus combined chemotherapy, n=24). The median dose of thalidomide
      was 200 mg (range, 150-400 mg) every night, without reported severe side effects.
      The clinical response to treatment was as follows: Complete response (CR) in 12
      cases, partial response (PR) in 7, stable disease (SD) in 1 and progressive
      disease (PD) in 4 cases in the thalidomide group; and CR in 8 cases, PR in 6, SD
      in 3 and PD in 5 cases in the control group. The CR rate was 50.0 and 36.4% in
      the thalidomide and the control groups, respectively (P<0.05). The median
      progression-free and overall survival were 12 and undefined months, respectively,
      in the thalidomide group and 6 and 17 months, respectively, in the control group.
      The toxicity profile was considered acceptable in both groups. Our results
      indicated that thalidomide plus combined chemotherapy may exhibit enhanced
      efficacy in the clinical treatment of T-NHL. In addition, this type of treatment
      may reduce the frequency of adverse gastrointestinal reactions and help alleviate
      fear of chemotherapy. Therefore, thalidomide plus combined chemotherapy may be a
      viable option for the clinical treatment of T-NHL.

PMID- 25054033
TI  - Health resource utilisation associated with skeletal-related events in European
      patients with lung cancer: Alpha subgroup analysis from a prospective
      multinational study.
AB  - Bone complications or skeletal-related events (SREs), typically defined as
      radiation to bone, pathological fractures, surgery to bone and spinal cord
      compression, occur frequently in patients with bone metastases. As the survival
      of patients with advanced lung cancer improves, preventing SREs is becoming
      increasingly clinically relevant. The aim of this analysis was to assess the
      impact of SREs on health resource utilisation (HRU) in European lung cancer
      patients with bone metastasis. This multinational, observational study included
      patients who had at least one SRE in the 97 days prior to enrolment, a life
      expectancy of >=6 months and an Eastern Cooperative Oncology Group performance
      status of 0-2. Data on HRU were retrospectively collected for up to 97 days prior
      to enrolment with a planned prospective follow-up for up to 18-21 months. The HRU
      measures included the number and length of inpatient hospitalisations and the
      number of outpatient visits and procedures. The investigators determined whether
      each HRU was attributable to a SRE. In total, 135 patients with lung cancer,
      enrolled at centres in Germany, Italy, Spain and the United Kingdom, contributed
      214 SREs to this analysis. The median length [quartile (Q)1, Q3] of follow-up
      ranged from 1.5 (0.7, 3.3) to 5.6 (2.0, 8.2) months across the countries.
      Overall, 41% of the SREs required an inpatient stay, with a median (Q1, Q3)
      duration of 19.0 (6.0, 28.0) days. Spinal cord compression and surgery to bone
      were the SRE types most frequently requiring inpatient stays. Radiation to bone
      was associated with the largest number of outpatient visits and procedures. All
      the SREs resulting from bone metastases in patients with lung cancer contribute
      considerably to HRU and efforts to minimise the incidence of bone complications
      in these patients through appropriate treatments may help reduce this burden.

PMID- 25054034
TI  - Zinc finger protein 185 is a liver metastasis-associated factor in colon cancer
      patients.
AB  - LIM domain proteins are involved in several fundamental biological processes,
      including cell lineage specification, cytoskeleton organization and organ
      development. Zinc finger protein 185 (ZNF185) is one of the LIM domain proteins
      considered to be involved in the regulation of cellular differentiation and/or
      proliferation. However, the detailed functions and properties of ZNF185 in the
      multistep process of cancer biology have not yet been elucidated. In this study,
      we analyzed the association between ZNF185 and the clinicopathological
      characteristics of colon cancer, such as patient age and gender, histological
      type, lymphatic and venous involvement, T and N status, liver metastasis and
      stage. ZNF185 protein expression was immunohistochemically analyzed and ZNF185
      was detected in the cancer cells of 78 of the 87 colon cancer patients. The
      correlation between ZNF185 and histological type was significant (P=0.010, G
      test). ZNF185 expression was also significantly correlated with liver metastasis
      (P=0.030, G-test). A multivariate analysis using the Cox proportional hazards
      model was performed among cause-specific survival rate, ZNF185 expression and
      clinicopathological characteristics. Histological type, liver metastasis and
      ZNF185 expression were found to be independent prognostic indicators (P=0.028,
      P<0.0001 and P=0.036, respectively). Therefore, ZNF185 expression was found to be
      an independent indicator of liver metastasis and prognosis in patients with colon
      cancer.

PMID- 25054035
TI  - Assessment of DDR2, BRAF, EGFR and KRAS mutations as therapeutic targets in non
      adenocarcinoma lung cancer patients.
AB  - Molecular-targeted therapy has not been established in non-adenocarcinoma lung
      cancer (non-AdLC), as no targets that affect the clinical efficacy of molecular
      targeted drugs have yet been identified. In this study, we investigated the
      frequency of genetic variations in discoidin domain receptor 2 (DDR2), v-raf
      murine sarcoma viral oncogene homolog B1 (BRAF), epidermal growth factor receptor
      (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in non
      AdLC patients, in order to evaluate the possibility of genetic mutations in these
      genes being used as therapeutic targets for the treatment of patients with non
      AdLC. For this purpose, we enrolled 150 non-AdLC patients who had undergone
      surgery at the Gunma University Hospital between December, 2003 and December,
      2012. Genetic mutations in the EGFR, KRAS, DDR2 and BRAF genes were detected by a
      sequencing method or probe assay using DNA derived from cancer tissues. No
      somatic mutations in DDR2 or BRAF were detected in non-AdLC patients. Conversely,
      genetic mutations in EGFR exon 19 were found in 3 squamous cell carcinoma (SCC)
      and 3 adenosquamous carcinoma patients, whereas KRAS codon 12 mutations were also
      found in 3 SCC patients and 1 large-cell neuroendocrine carcinoma patient. EGFR
      and KRAS mutations were mutually exclusive. This study indicated that, although
      DDR2 and BRAF mutations may only rarely be used as therapeutic targets, EGFR and
      KRAS mutations may represent candidate therapeutic targets, at least in the non
      AdLC patients investigated.

PMID- 25054036
TI  - Docetaxel, cisplatin and 5-fluorouracil adjuvant chemotherapy following three
      field lymph node dissection for stage II/III N1, 2 esophageal cancer.
AB  - To determine the efficacy of postoperative adjuvant chemotherapy with docetaxel +
      cisplatin + 5-fluorouracil (DCF) in lymph node metastasis-positive esophageal
      cancer, we retrospectively analyzed 139 patients with stage II/III (non-T4)
      esophageal cancer with lymph node metastasis (1-6 nodes), who did not receive
      preoperative treatment and underwent three-field lymph node dissection in the
      Juntendo University Hospital between December, 2004 and December, 2009. The
      tumors were histologically diagnossed as squamous cell carcinoma. The patients
      were divided into two groups, a surgery alone group (S group, 88 patients) and a
      group that received postoperative DCF therapy (DCF group, 51 patients). The
      disease-free and overall survival were compared between the groups and a
      multivariate analysis of prognostic factors was performed. The same analysis was
      performed for cases classified as N1 and N2, according to the TNM classification.
      There were no significant differences between the S and DCF groups regarding
      clinicopathological factors other than intramural metastasis and main tumor
      location. The presence of intramural metastasis, blood vessel invasion and the
      number of lymph nodes were identified as prognostic factors. The 5-year disease
      free and overall survival were 55.8 and 57.3%, respectively, in the S group and
      52.8 and 63.0%, respectively, in the DCF group. These differences were not
      considered to be statistically significant (P=0.789 and 0.479 for disease-free
      and overall survival, respectively). Although there were no significant
      differences in disease-free and overall survival between the S and DCF groups in
      N1 cases, both disease-free and overall survival were found to be better in the
      DCF group (54.2 and 61.4%, respectively) compared to the S group (29.6 and 28.8%,
      respectively) in N2 cases (P=0.029 and 0.020 for disease-free and overall
      survival, respectively). Therefore, postoperative adjuvant chemotherapy with DCF
      was shown to improve disease-free and overall survival in moderate lymph node
      metastasis-positive cases (N2), suggesting that the DCF regimen may be effective
      as postoperative adjuvant chemotherapy for patients with lymph node metastasis
      from esophageal cancer.

PMID- 25054037
TI  - Investigation of neurotrophic tyrosine kinase receptor 1 fusions and neurotrophic
      tyrosine kinase receptor family expression in non-small-cell lung cancer and
      sensitivity to AZD7451 in vitro.
AB  - Advances in the molecular segmentation of lung cancer has raised the possibility
      that neurotrophic tyrosine kinase receptor (NTRK) 1 fusions and NTRK1-3
      expression may be promising molecular targets for future therapeutic
      interventions. We investigated the antitumor effects of a selective pan-NTRK
      inhibitor, AZD7451, by evaluating its antiproliferative effects on the KM12 cell
      line (a colorectal cancer cell line harboring a tropomyosin-NTRK1 fusion) and the
      H460 and H810 cell lines [large-cell neuroendocrine carcinoma (LCNEC) cell lines
      expressing NTRK2]. Relative quantitative polymerase chain reaction (qPCR) was
      performed to measure the mRNA levels of the NTRK1-3 tyrosine kinase domain using
      cDNA extracted from KM12, H460 and H810 cells. The cultures were grown in 6-well
      plates at a density of 1.0*106 cell/well and treated with AZD7451 at different
      doses (1, 2.5, 4, 5, 7.5 and 10 nM) using dimethyl sulfoxide as a control.
      Following a 24-h incubation, the number of surviving cells was measured using a
      hemocytometer. Furthermore, we performed western blotting of the high-affinity
      nerve growth factor receptor (TRKA) and NTRK2 (TRKB) proteins and monitored the
      effects on the downstream signaling pathways Akt and ERK in these cell lines
      following treatment with AZD7451 (KM12 and H460: 0, 1 and 5 nM; H810: 0 and 5
      nM). Immunohistochemical analyses of the surgically resected samples were also
      performed, using anti-NTRK1,2 antibodies. We performed reverse-transcription PCR
      and direct sequencing to investigate NTRK fusions in 268 patients; however, were
      unable to confirm the presence of NTRK fusions in this cohort. Further
      immunohistochemical analyses of the primary patient samples demonstrated that
      none of 61 tumors had NTRK1 overexpression and 7 of 39 samples exhibited NTRK2
      expression, including 1 LCNEC sample. The qPCR results from the KM12 cell line
      revealed an apparent increase and overexpression of NTRK1 mRNA levels, while H460
      cells exhibited a modest increase and the H810 cell line showed no apparent
      increase in the expression of any NTRK1-3 isoforms. There were no increases in
      the NTRK2 mRNA levels in any of the three cell lines, although KM12 and H460
      cells exhibited low levels of NTRK2 expression. In vitro growth and proliferation
      of the KM12 cell line harboring the NTRK1-fusion was found to be potently
      inhibited by AZD7451 at a concentration of 2 nM. The proliferation of H460 cells
      was also found to be inhibited at a concentration of 5 nM, while there was no
      apparent inhibitory effect of AZD7451 on the growth or proliferation of H810
      cells. Western blotting of KM12 cells treated with AZD7451 also revealed a potent
      inhibition of TRKA phosphorylation following AZD7451 treatment. Analysis of H460
      cells confirmed the expression and inhibition of phosphorylation of NTRK2,
      whereas there was little to no expression of TRKA/B in H810 cells. Subsequent in
      vitro analysis of cell lines treated with the pan-TRK inhibitor AZD7451 suggested
      that the proliferation of KM12 and H460 cells was significantly inhibited by
      AZD7451, while H810 cells expressing low levels of wild-type NTRK1-3 were not
      inhibited. Based on these results, there is potential for a NTRK-dependent
      proliferation driver in a subpopulation of lung cancer patients with NTRK
      expression. In addition, pharmacological inhibition with a NTRK inhibitor, such
      as AZD7451, in cells harboring NTRK1 fusions, may be associated with beneficial
      antitumor effects.

PMID- 25054038
TI  - Surrogate endpoints for overall survival in advanced non-small-cell lung cancer
      patients with mutations of the epidermal growth factor receptor gene.
AB  - Subsequent therapies confound the ability to discern the effect of first-line
      chemotherapy on overall survival (OS). We investigated whether progression-free
      survival (PFS), post-progression survival (PPS) and tumor response were valid
      surrogate endpoints for OS following first-line chemotherapy in individual
      patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive
      epidermal growth factor receptor gene mutations. We retrospectively analyzed 35
      patients with advanced NSCLC treated with first-line gefitinib. The associations
      of PFS, PPS and tumor response with OS were analyzed. PPS was found to be
      strongly correlated with OS, unlike PFS and tumor shrinkage. The factors
      significantly associated with PPS were performance status (PS) after first-line
      treatment, best response to second-line treatment and number of regimens used
      after disease progression. PPS may be a surrogate for OS in this patient
      population and further therapy after disease progression following first-line
      chemotherapy may significantly affect OS. However, a larger study is required to
      validate these results.

PMID- 25054039
TI  - Clinical usefulness of testing for UDP glucuronosyltransferase 1 family,
      polypeptide A1 polymorphism prior to the inititation of irinotecan-based
      chemotherapy.
AB  - An association between UDP glucuronosyltransferase 1 family, polypeptide A1
      (UGT1A1) polymorphisms and irinotecan-induced neutropenia has been previously
      reported. In this study, we assessed the clinical usefulness of testing for
      UGT1A1 polymorphisms prior to the initiation of irinotecan-based chemotherapy, as
      this remains a controversial subject. A total of 136 lung cancer patients who
      were treated with a combination of nedaplatin and irinotecan as initial
      chemotherapy were assessed. Following exclusion of patients exhibiting low UGT1A1
      enzyme activity, 70 patients were treated after UGT1A1 polymorphism testing (test
      group) and 66 patients were treated without UGT1A1 polymorphism testing (non-test
      group). We retrospectively analyzed and compared the adverse events between the
      test and the non-test groups and observed no reduction in hematological or non
      hematological toxicities in the test group compared to that in the non-test
      group. Of the 9 patients with grade 4 or 5 non-hematological toxicity, 6 patients
      had febrile neutropenia (FN). All the patients with FN were aged >70 years. The
      incidence of adverse events was significantly higher among patients aged >70
      years compared to that among younger patients. In conclusion, in patients treated
      with nedaplatin and irinotecan combination chemotherapy, UGT1A1 polymorphism
      testing prior to the initiation of chemotherapy did not reduce the incidence of
      adverse events. Therefore, UGT1A1 polymorphism testing alone may not be
      sufficient to predict the occurrence of severe adverse events and it may be more
      important to effectively manage adverse events, particularly in elderly patients.

PMID- 25054040
TI  - Cyclooxygenase-2 inhibitors for non-small-cell lung cancer: A phase II trial and
      literature review.
AB  - Several preclinical and clinical studies have demonstrated that cyclooxygenase-2
      (COX-2) inhibitors are efficient for the treatment of non-small-cell lung cancer
      (NSCLC). However, two recent phase III clinical trials using COX-2 inhibitors in
      combination with platinum-based chemotherapy failed to demonstrate a survival
      benefit. Thus, validation and discussion regarding the usefulness of COX-2
      inhibitors for patients with NSCLC are required. We conducted a prospective trial
      using COX-2 inhibitors for the treatment of 50 NSCLC patients accrued between
      April, 2005 and July, 2006. Patients with untreated advanced NSCLC received oral
      meloxicam (150 mg daily), carboplatin (area under the curve = 5 mg/ml * min on
      day 1) and docetaxel (60 mg/m2 on day 1) every 3 weeks. The primary endpoint was
      response rate. The response and disease control rates were 36.0 and 76.0%,
      respectively. The time-to-progression (TTP) and overall survival (OS) were 5.7
      months [95% confidence interval (CI): 4.6-6.7] and 13.7 months (95% CI: 11.4
      15.9), respectively. The 1-year survival ratio was 56.0%. Grade 3 neuropathy was
      observed in only 1 patient. We performed tumor immunohistochemistry for COX-2 and
      p27 and investigated the correlation between their expression and clinical
      outcome. COX-2 expression in the tumor tended to correlate with a higher response
      rate (50.0% in the high- and 18.2% in the low-COX-2 group; P=0.092). Based on our
      results and previous reports, various trial designs, such as the prospective use
      of COX-2 inhibitors only for patients with COX-2-positive NSCLC, including the
      exploratory analysis of biomarkers associated with the COX-2 pathway, may be
      worth further consideration.

PMID- 25054041
TI  - Expression of human epidermal growth factor receptor 2 in primary and paired
      parenchymal recurrent and/or metastatic sites of gastric cancer.
AB  - Human epidermal growth factor receptor 2 (HER2) status has been evaluated at the
      primary site of gastric cancer when planning trastuzumab therapy against
      recurrent or metastatic lesions, since tissue sampling is uncommon in recurrent
      or metastatic lesions. This study retrospectively investigated the concordance of
      HER2 expression between primary and metastatic/recurrent lesions in order to
      confirm sensitivity to trastuzumab. The subjects comprised 37 patients with
      gastric adenocarcinoma who underwent tissue biopsy or surgical resection of the
      primary sites and 49 paired synchronous or metachronous metastatic sites
      (excluding lymph nodes) at the Fukuoka University Hospital between January, 1998
      and September, 2012. All the samples were evaluated for HER2 status at the
      invasive front by immunohistochemistry (IHC). The HER2 positivity rate of the
      primary sites was ~16% and the concordance ratio of the IHC results between
      primary and paired metastatic sites was ~97%. No discordant cases regarding HER2
      status were found among metachronous interventions for metastatic lesions. Only
      one patient exhibited conversion from a HER2-negative status in all the portions
      of the primary site to a positive status in a metastatic site. In conclusion, a
      high concordance ratio for HER2 status was observed between primary and paired
      metastatic lesions. Thus, employing trastuzumab therapy against metastatic or
      recurrent gastric cancer based on the HER2 status of the primary lesion appears
      to be an acceptable approach.

PMID- 25054042
TI  - Prognostic role of lemur tyrosine kinase 3 in postoperative gastric cancer.
AB  - The treatment of gastric cancer has been unsatisfactory thus far; therefore,
      novel targets and treatment strategies are urgently required. Lemur tyrosine
      kinase (LMTK)3 is an estrogen receptor-alpha (ERalpha) modulator with a central
      role in endocrine resistance in breast cancer. Moreover, the expression and
      polymorphisms of LMTK3 are correlated with the prognosis of breast cancer
      patients. Since estrogen receptor (ER) is also expressed and plays a role in
      gastric cancer, we herein investigated the expression of the LMTK3 protein in 83
      gastric cancer patients by tissue microarray and analyzed the correlation between
      LMTK3 expression and the prognosis of gastric cancer. Our results demonstrated
      that LMTK3 was more frequently expressed in gastric cancer tissues compared to
      non-cancerous mucosa (79.5 vs. 45.8%, respectively; P=0.000). The LMTK3
      expression was significantly correlated with the depth of invasion (P=0.002) and
      disease stage (P=0.035). The Kaplan-Meier analysis revealed that the
      postoperative survival of the LMTK3-negative group was superior to that of the
      LMTK3-positive group (P=0.043). Moreover, the multivariate analysis identified
      LMTK3 expression as an independent prognostic factor for patients with gastric
      cancer (P=0.019). These findings suggested that the expression of LMTK3 may be a
      negative prognostic factor in patients with gastric cancer. Moreover, targeting
      LMTK3 is a potential strategy for the treatment of gastric cancer, although the
      biological functions of LMTK3 in gastric cancer require further investigation.

PMID- 25054043
TI  - The value of 18F-fluorodeoxyglucose positron emission tomography combined with
      computed tomography in the detection and characterization of soft tissue
      metastasis.
AB  - Metastatic tumours presenting as soft tissue metastasis (STM) are relatively
      rare. STM represents metastasis to the muscle and subcutaneous tissues. The
      majority of the currently available clinical or radiological data on STM consist
      of isolated case reports or reviews. The aim of this study was to report the
      manifestations, origin and distribution of STM detected by 18F-fluorodeoxyglucose
      (FDG) positron emission tomography (PET)/computed tomography (CT) and to assess
      the value of 18F-FDG PET/CT in the characterisation of STM. We reviewed 17 cases
      of patients with STM who underwent 18F-FDG PET/CT scanning. The imaging and
      clinical data of these patients were retrospectively analysed. This method is
      very sensitive in the detection of STM and provides ample information for
      clinical tumour staging. PET is more sensitive compared to CT in detecting
      lesions in muscle, before the density and morphology of the soft tissues are
      altered, providing a clear view within the soft tissue. Due to the limitations in
      resolution, PET is less sensitive compared to CT in detecting lesions in the
      subcutaneous tissues. The aim of this study was to improve our knowledge of 18F
      FDG PET/CT findings in the diagnosis of STM and determine its value in the
      staging of malignant tumours.

PMID- 25054044
TI  - High expression of peroxiredoxin 4 affects the survival time of colorectal cancer
      patients, but is not an independent unfavorable prognostic factor.
AB  - Peroxiredoxin 4 (Prx4) has a number of important biological functions, such as
      efficient antioxidant capacity and promotion of cell proliferation and
      differentiation. The purpose of this study was to investigate the expression and
      significance of Prx4 in human colorectal cancer (CRC). Quantitative polymerase
      chain reaction (qPCR) was performed to detect Prx4 in 8 freshly frozen specimens
      of CRC and their adjacent normal tissues. In addition, immunohistochemical
      analysis was performed to detect Prx4 in 59 specimens of CRC and 26 of adjacent
      normal tissues. The immunohistochemical and qPCR results demonstrated that the
      expressions of the Prx4 gene and protein were higher in CRC compared to those in
      the adjacent normal tissues. The expression intensity of the Prx4 protein was
      correlated with depth of invasion (P=0.001), lymph node metastasis (P=0.006) and
      Dukes' classification (P=0.004) in CRC. The Kaplan-Meier survival curves revealed
      that high Prx4 expression was correlated with short survival time. However, the
      Cox proportional hazards regression analysis did not identify Prx4 as an
      independent prognostic marker for CRC (P>0.05). These results suggested that Prx4
      may be associated with carcinogenesis and the development of CRC and it may be a
      prognostic marker for postoperative CRC patients.

PMID- 25054046
TI  - Magnetic resonance imaging shrinkage patterns following neoadjuvant chemotherapy
      for breast carcinomas with an emphasis on the radiopathological correlations.
AB  - Preoperative neoadjuvant chemotherapy (NAC) is considered to be the standard
      treatment for locally-advanced breast carcinomas. Obtaining precise information
      regarding the tumor extent and distribution by imaging modalities to assess the
      success of breast-conserving surgery following NAC is extremely important.
      Analysis of the detailed radiopathological correlation of magnetic resonance
      imaging (MRI) following NAC has not been reported previously. The MRI and
      histopathological shrinkage patterns of residual breast carcinomas in 27
      consecutive cases were analyzed following NAC and classified into five
      categories: Types I and II (concentric shrinkage with and without surrounding
      lesions, respectively); type III (shrinkage with residual multinodular lesions);
      type IV (diffuse contrast enhancement in whole quadrant); and non-visualization.
      The present study clearly demonstrated that the most common MRI shrinkage pattern
      was type I (11 cases), followed by type II and non-visualization, and the most
      common histopathological shrinkage pattern was type II (11 cases), followed by
      type III (8 cases). The concordance rate between MRI and pathological patterns
      was 48% and the worst concordance MRI pattern was type I. MRI is considered to be
      a useful method for evaluation of the residual carcinoma following NAC. However,
      the concordance rate was low in the MRI pattern I cases and tiny foci of residual
      carcinoma were present in half of the non-visualization cases, as shown by MRI.
      Therefore, the tumor extent must be completely resected for patients who undergo
      NAC, and postoperative radiation may be important for preventing local recurrence
      of breast carcinoma.

PMID- 25054045
TI  - Conditioning with treosulfan and fludarabine for patients with refractory or
      relapsed non-Hodgkin lymphoma.
AB  - The treatment of refractory or relapsed non-Hodgkin lymphoma (NHL) remains
      challenging. In this retrospective study, 88 patients with refractory or relapsed
      NHL received treosulfan and fludarabine as a reduced-intensity conditioning for
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). Of the 88
      intensely pre-treated patients, 73 experienced a relapse, with 18 of the 88
      patients experiencing an early relapse (ER; <6 months from the last
      chemotherapy). At the time of allo-HSCT, 26 patients were in complete remission
      (CR) and 43 in partial remission (PR), 12 patients had progressive disease (PD)
      and 7 had stable disease (SD). A total of 47 patients received an autologous
      graft followed by allo-HSCT. Following allo-HSCT, 69 of the 88 patients were in
      CR and 7 were in PR, resulting in an overall response rate of 86.4% (76/88). A
      total of 33 patients achieved a CR from PR, as did 6 patients from PD and 5 from
      SD. Of the 88 patients, 43 (49%) were alive at the end of the follow-up period.
      The patients who directly underwent allo-HSCT without prior auto-HSCT exhibited a
      better disease-free survival (DFS; P=0.038) with a tendency (P=0.077) for a
      better overall survival (OS). The patients with ER exhibited a probability of OS
      of 0.35+/-0.12 after 3 and 7 years. Chronic graft-versus-host disease (cGvHD)
      exerted a positive effect on OS and DFS (for limited cGvHD vs. no cGvHD, P=0.002
      and 0.004, respectively). In conclusion, allogeneic stem cell transplantation
      following conditioning with treosufan and fludarabine constitutes a viable
      therapeutic option for patients with refractory or relapsed NHL and should be
      considered early during the course of salvage treatment.

PMID- 25054047
TI  - A risk score model for the metastasis of level Ib lymph node based on the
      clinicopathological features of nasopharyngeal carcinoma in a large sample.
AB  - The aim of the present study was to develop a metastatic risk score model of neck
      level Ib lymph nodes in primary nasopharyngeal carcinoma (NPC) to guide the level
      Ib radiotherapy. There were a total of 1,557 patients enrolled in the study, and
      of these patients, 1,145 were included in the training set. Univariate chi2
      analysis and multivariate logistic regression analyses were used to screen the
      independent risk factors to construct the risk score model. A total of 85
      patients in the validating set underwent a pathology biopsy of level Ib lymph
      nodes to test the model. The remaining 327 patients from the prognostic-research
      set were used to evaluate the prognostic impact of level Ib irradiation in high-
      and low-risk groups. The independent risk factors in the model were carotid
      sheath involvement, the maximal diameter of the neck lymph nodes (>=20 mm) and
      the involvement of the level II/III/IV lymph nodes. The involvement of level IV
      was assigned score 2 and the other risk factors were assigned score 1. According
      to the total scores, the patients were divided into the low- (total score, 0-1;
      level Ib metastasis rate, 0.5%) and high-risk groups (total score, 2-4; level Ib
      metastasis rate, 8.5%). In the validating set, the metastatic rate of level Ib in
      43 low-risk patients was 0%, and the rate was 31.0% (13/42) in 42 high-risk
      patients. In the prognostic-research set, the prognosis of 137 low-risk patients
      was not affected by level Ib irradiation. However, level Ib unirradiation was an
      independent prognostic factor for the locoregional recurrence in 190 high-risk
      patients. According to the data, the novel score model could help assess the
      metastatic risk of level Ib in primary NPC, and the radiotherapy on level Ib may
      impact the locoregional recurrence in high-risk patients.

PMID- 25054048
TI  - 18F-FDG-PET/CT predicts the distribution of microsatellite lesions in
      hepatocellular carcinoma.
AB  - This study was conducted to investigate whether fluorine-18 fluorodeoxyglucose
      positron emission tomography/computed tomography (18F-FDG PET/CT) is useful for
      predicting the distance of intrahepatic metastases and microvascular invasion
      from the main tumor and the pattern of postoperative recurrence. A total of 89
      consecutive patients who underwent 18F-FDG PET/CT prior to liver resection for
      hepatocellular carcinoma (HCC) between April, 2006 and December, 2011 were
      enrolled in this study. The distance between the microsatellite lesion and the
      main nodule (microsatellite distance) was analyzed and measured pathologically.
      The correlation between maximal standardized uptake values (SUVmax) and
      microsatellite distance was analyzed and the independent risk factors for
      microsatellite distance >1 cm were assessed. The postoperative recurrence
      patterns were divided into no recurrence, intrahepatic recurrence and
      extrahepatic recurrence. SUVmax and the distribution of microsatellite lesions
      were compared among these groups. The postoperative recurrence patterns were also
      analyzed according to the SUVmax and the microsatellite lesion pattern. SUVmax
      was found to be significantly correlated with the distance from the
      microsatellite lesion to the main nodule (r=0.57, P<0.0001). On the multivariate
      analysis of microsatellite distance >1 cm, the only significant factor was SUVmax
      [P=0.002; hazard ratio=1.60; 95% confidence interval (CI): 1.23-2.26]. The
      optimal cutoff value of SUVmax for microsatellite distance >1 cm was 8.8. The
      mean SUVmax and the microsatellite distance were highest in patients with
      postoperative extrahepatic metastases (8.6 and 9,160 MUm, respectively). In
      conclusion, the SUVmax of 18F-FDG PET/CT reflects microsatellite distance and the
      patterns of postoperative recurrence in HCC. Therefore, 18F-FDG PET/CT may be a
      useful imaging modality for determining the resection margin and the treatment
      protocol for HCC.

PMID- 25054049
TI  - A meta-analysis of randomized controlled trials comparing early and late
      concurrent thoracic radiotherapy with etoposide and cisplatin/carboplatin
      chemotherapy for limited-disease small-cell lung cancer.
AB  - The aim of the present study was to determine the optimal time for concurrent
      thoracic radiotherapy (TRT) with etoposide and cisplatin/carboplatin (EP/EC)
      chemotherapy for the treatment of limited-disease small-cell lung cancer (LD
      SCLC). Randomized controlled trials comparing early and late concurrent TRT with
      EP/EC chemotherapy for the treatment of patients with LD SCLC were identified
      through searching databases such as MEDLINE, the Cochrane Central Register of
      Controlled Trials and Embase. Early thoracic radiotherapy (ERT) was defined as
      initiating irradiation within 30 days after chemotherapy initiation. A total of 3
      eligible randomized controlled trials were identified. No significant differences
      in the objective response rate were detected between early and late concurrent
      TRT [risk ratio (RR)=1.01; 95% confidence interval (CI): 0.86-1.18; P=0.90].
      Similar results were observed in the 1-, 2-, 3- and 5-year survival rates between
      early and late concurrent TRT (RR=1.06, 95% CI: 0.88-1.27, P=0.56; RR=1.15, 95%
      CI: 0.77-1.71, P=0.49; RR=0.90, 95% CI: 0.66-1.22, P=0.49; and RR=1.18, 95% CI:
      0.64-2.16, P=0.60, respectively). The total incidence of grade 3-4 adverse
      events, including anemia, leukopenia, neutropenia, thrombocytopenia, nausea and
      vomiting, infection, esophageal toxicity, pulmonary toxicity, alopecia and
      hemorrhage with early concurrent TRT was significantly higher compared to that
      with late concurrent TRT (RR=1.21, 95% CI: 1.03-1.43, P=0.02). Thus, the results
      of our study indicated that the prognosis of LD SCLC treated with late concurrent
      TRT and EP/EC chemotherapy is similar to that with early concurrent TRT, although
      the incidence of grade 3-4 adverse events was lower in LD SCLC patients treated
      with late concurrent TRT combined with EP/EC chemotherapy.

PMID- 25054050
TI  - Osteosarcoma with metastasis at initial diagnosis: Current outcomes and
      prognostic factors in the context of a comprehensive cancer center.
AB  - The aim of this study was to report the outcomes and prognostic factors for a
      cohort of patients with osteosarcoma who presented with metastasis at initial
      diagnosis. Data of consecutive patients with osteosarcoma and metastatic disease
      at initial presentation, who were treated and followed up at a single
      institution, were retrospectively reviewed. The effect of potential factors on
      overall survival (OS) was analyzed through univariate and multivariate analysis.
      Between January, 2000 and March, 2013, a total of 135 patients with osteosarcoma,
      of whom 21 (16.0%) had distant metastasis at initial presentation, were diagnosed
      and treated at our center and were included in this analysis. The patients were
      treated with a strategy that integrates multi-agent chemotherapy and resection of
      all sites of gross disease whenever feasible. The 5-year OS and event-free
      survival (EFS) were 23.0% and 11.0%, respectively. The factors associated with
      inferior OS in the univariate analysis included the osteoblastic variant,
      extrapulmonary metastasis and failure to achieve complete remission. In the
      multivariate analysis, the osteoblastic variant [hazard ratio (HR)=4.83, 95%
      confidence interval (CI): 1.16-20.0, P=0.038] and extrapulmonary metastasis
      (HR=5.0, 95% CI: 1.40-17.94, P=0.018) were the only independent prognostic
      factors. The current outcomes of patients with osteosarcoma and metastasis at
      initial diagnosis remained poor. The osteoblastic subtype and extrapulmonary
      metastatic sites predicted poor survival in our series. To the best of our
      knowledge, this is the first report of the correlation between the histological
      subtype and survival for patients with metastatic disease at initial
      presentation; therefore, confirmation in future studies is required.

PMID- 25054051
TI  - Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in
      colorectal cancer patients.
AB  - Bmi1 is overexpressed in gastrointestinal cancers, including colorectal cancer
      (CRC); however, its role as a non-invasive biomarker in CRC has not been
      established. The aim of this study was to compare the plasma Bmi1 mRNA levels
      prior to and following curative resection of the primary tumor in CRC patients
      and to determine their association with the clinicopathological parameters. The
      plasma Bmi1 mRNA level was measured by quantitative polymerase chain reaction and
      expressed as cycle threshold value. There was no significant difference between
      the overall pre- and postoperative plasma Bmi1 mRNA level (31.73+/-2.63 vs.
      31.93+/-2.88, respectively; P=0.614) in 45 CRC patients. However, when grouped
      into non-metastatic and metastatic CRC patients, the postoperative Bmi1
      transcript level was found to be significantly lower compared to the preoperative
      level in patients with non-metastatic CRC (32.13+/-2.677 31.44+/-2.764,
      respectively; P=0.041), whereas there was a trend towards a higher postoperative
      Bmi1 transcript level compared to the preoperative level in the metastatic
      counterpart (30.85+/-3.916 vs. 33.27+/-0.718, respectively; P=0.164).
      Furthermore, when the patients were categorized into two groups according to
      their plasma Bmi1 postoperative vs. preoperative level status, we observed that
      patients without a reduction in the postoperative plasma Bmi1 mRNA levels
      exhibited a significantly higher rate of distant metastasis following primary
      resection (P=0.017) and a significantly worse prognosis regarding disease-free
      survival (P=0.016) when compared to the reduced postoperative plasma Bmi1 level
      counterparts. In conclusion, plasma Bmi1 mRNA levels may serve as a non-invasive
      biomarker for monitoring occult metastasis and predicting the development of
      distant metastasis.

PMID- 25054052
TI  - Characterization of lymph node metastasis and its clinical significance in the
      surgical treatment of gastric cancer.
AB  - This study aimed to characterize lymph node metastasis and determine its clinical
      significance in the surgical treatment of gastric cancer. The medical charts of
      920 gastric cancer patients who underwent radical surgical resection between
      March, 2010 and March, 2013, were retrospectively reviewed and statistically
      analyzed. Lymphatic metastasis was observed in 69.6% of the patients (640/920).
      The frequency of lymph node metastasis in patients with early-stage gastric
      cancer was 21.4% (18/84). Lymph node metastasis was observed in all the patients
      with stage IIIC-IV gastric cancer. The incidence of lymph node metastasis was
      higher among patients with tumors >7 cm in size. The most frequently affected
      lymph nodes in patients with proximal, central and distal gastric cancer were
      station no. 1 (34.2%), no. 3 (33.8%) and no. 6 (34.3%) lymph nodes, respectively.
      The frequency of lymph node metastasis in patients with Borrmann type IV cancer
      was significantly higher compared to that in patients with other Borrmann type
      cancers. Our study further demonstrated that lymphatic metastasis is closely
      correlated with TNM stage, location, depth of invasion and size of gastric
      tumors. Therefore, we recommend that a sufficient number of lymph nodes be
      examined from each patient to determine the extent of lymph node dissection based
      on Borrmann type, location, size, depth of invasion and histology of the cancer.

PMID- 25054053
TI  - XELIRI regimen plus continuous treatment with bevacizumab is well-tolerated and
      effective in metastatic colorectal cancer patients in a second-line setting
      involving the sequential administration of XELOX and XELIRI.
AB  - The aim of the present study was to present a retrospective review of 42
      metastatic colorectal cancer (mCRC) patients treated using the XELIRI regimen as
      second-line chemotherapy during the period between 2010 and 2012. Patients were
      treated with capecitabine, 1,600 (>=65 years) or 2,000 mg/m2 (<65 years), on days
      1-15, 200 mg/m2 irinotecan (CPT-11) on day 1, with or without 7.5 mg/kg
      bevacizumab on day 1 and every 21 days. A total of 21 patients underwent XELIRI
      and 21 underwent XELIRI plus bevacizumab treatment. Fifteen patients received
      continuous administration of bevacizumab in the first- and second-line settings
      [bevacizumab beyond progression (BBP)+], whereas 27 patients did not receive the
      treatment (BBP-). Forty patients (95.2%), including all the patients in the BBP+
      group, received sequentially administered XELOX and XELIRI regimens from the
      first- to the second-line setting. The disease control rate (DCR), progression
      free survival (PFS), overall survival (OS) and adverse events were compared
      between the BBP- and BBP+ groups. The median relative dose intensity was similar
      (93.9% for capecitabine and 96.3% for CPT-11 in the BBP- group vs. 94.8% for
      capecitabine and 91.5% for CPT-11 in the BBP+ group). The DCR was 25.9% in the
      BBP- and 66.6% in the BBP+ groups (P=0.020). The median PFS was 3.5 months in the
      BBP- and 7.2 months in the BBP+ groups (P=0.028). The BBP+ group exhibited a
      higher median OS time compared to the BBP- group (12.5 months in the BBP- group
      vs. not reached in the BBP+ group; P=0.0267). The most common grade 3/4 adverse
      event (n>=20) was hypertension observed in the BBP+ group [three patients (20%)]:
      these three patients were well-controlled with a single antihypertensive drug.
      Treatment with sequentially administered XELOX and XELIRI regimens did not
      aggravate adverse events in the 40 patients. The results showed that the XELIRI
      regimen, involving continuous treatment with bevacizumab, was well-tolerated and
      effective as a second-line chemotherapy and sequentially administering XELOX and
      XELIRI was feasible and manageable for patients with mCRC.

PMID- 25054054
TI  - Mesohepatectomy for the treatment of patients with centrally located
      hepatocellular carcinoma.
AB  - Mesohepatectomy is considered a feasible option for patients with centrally
      located hepatocellular carcinoma (HCC). However, mesohepatectomy is a technically
      demanding and less frequently used procedure. In this study, we summarized the
      surgical experience and evaluated the clinical outcomes of mesohepatectomy in 24
      patients with centrally located HCC. Of these patients, 9 were treated with
      hepatectomy of Couinaud's segments IV, V and VIII with concurrent
      cholecystectomy; 8 underwent resection of segments IVb, V and VIII, including 7
      patients who also received a cholecystectomy; 4 underwent hepatectomy of segments
      IVa, V and VIII; and 3 patients were treated with hepatectomy of segments I, IV,
      V and VIII, with concurrent cholecystectomy. The Pringle maneuver was used on 17
      patients during hepatectomy. Total hepatic vascular exclusion (HVE) was performed
      on 3 patients and HVE was not used on 4 patients. The average mesohepatectomy
      operative time was 238 min and the average intraoperative blood loss was 480 ml
      (200-2,200 ml). There was no intraoperative mortality and the postoperative
      morbidity rate was 25% (6/24). The 1- and 3-year overall survival rates were 76
      and 46%, respectively. Therefore, mesohepatectomy is a safe and effective
      surgical procedure for the treatment of centrally located HCC and HVE during
      mesohepatectomy for centrally located HCC is crucial to the success of the
      operation and postoperative patient recovery.

PMID- 25054055
TI  - Stereotactic body radiotherapy combined with transarterial chemoembolization for
      huge (>=10 cm) hepatocellular carcinomas: A clinical study.
AB  - This study was conducted to evaluate the safety and efficacy of stereotactic body
      radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) for huge
      (>=10 cm) hepatocellular carcinomas (HCCs). Between May, 2006 and December, 2012,
      72 patients with huge HCCs were treated by SBRT following incomplete TACE. The
      median total dose of 35.6 Gy was delivered over 12-14 days with a fractional dose
      of 2.6-3.0 Gy and 6 fractions per week. The patients were classified into those
      with tumor encapsulation (group A, n=33) and those without tumor encapsulation
      (group B, n=39). The clinical outcomes of tumor response, overall cumulative
      survival and toxicities/complications were retrospectively analyzed. Among the 72
      patients, CR, PR, SD and PD were achieved in 6 (8.3%), 51 (70.8%), 9 (12.5%) and
      6 patients (8.3%), respectively, within a median follow-up of 18 months. The
      objective response rate was 79.1%. The overall cumulative 1-, 3- and 5-year
      survival rates and the median survival time were 38, 12 and 3% and 12.2 months,
      respectively. In group A, the overall cumulative 1-, 3- and 5-year survival rates
      were 56, 21 and 6%, respectively, with a median survival of 19 months; in group
      B, the overall cumulative 1-, 3- and 5-year survival rates were 23, 4 and 0%,
      respectively, with a median survival of 10.8 months (P=0.023). The treatment was
      well tolerated, with no severe radiation-induced liver disease and no reported >
      grade 3 toxicity. Tumor encapsulation was found to be a significant prognostic
      factor for survival. In conclusion, the combination of SBRT and TACE was shown to
      be a safe and effective treatment option for patients with unresectable huge HCC.

PMID- 25054056
TI  - Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer
      patients.
AB  - Triple-negative breast cancer (TNBC) is characterised by lack of estrogen
      receptor (ER), progesterone receptor (PR) and human epidermal growth factor
      receptor (HER)2/neu gene amplification. TNBC patients typically present at a
      younger age, with a larger average tumor size, higher grade and higher rates of
      lymph node positivity compared to patients with ER/PR-positive tumors.
      Cyclooxygenase (COX)-2 regulates the production of prostaglandins and is
      overexpressed in a variety of solid tumors. In breast cancer, the overexpression
      of COX-2 is associated with indicators of poor prognosis, such as lymph node
      metastasis, poor differentiation and large tumor size. Since both TNBC status and
      COX-2 overexpression are known poor prognostic markers in primary breast cancer,
      we hypothesized that the COX-2 protein is overexpressed in the primary tumors of
      TNBC patients. The purpose of this study was to determine whether there exists an
      association between TNBC status and COX-2 protein overexpression in primary
      breast cancer. We prospectively evaluated COX-2 expression levels in primary
      tumor samples obtained from 125 patients with stage I-III breast cancer treated
      between February, 2005 and October, 2007. Information on clinicopathological
      factors was obtained from a prospective database. Baseline tumor characteristics
      and patient demographics were compared between TNBC and non-TNBC patients using
      the Chi-square and Fisher's exact tests. In total, 60.8% of the patients were
      classified as having ER-positive tumors, 51.2% were PR-positive, 14.4% had HER
      2/neu amplification and 28.0% were classified as TNBC. COX-2 overexpression was
      found in 33.0% of the patients. TNBC was associated with COX-2 overexpression
      (P=0.009), PR expression (P=0.048) and high tumor grade (P=0.001). After
      adjusting for age, menopausal status, body mass index (BMI), lymph node status
      and neoadjuvant chemotherapy (NACT), TNBC was an independent predictor of COX-2
      overexpression (P=0.01). In conclusion, the association between TNBC and COX-2
      overexpression in operable breast cancer supports further investigation into COX
      2-targeted therapy for patients with TNBC.

PMID- 25054057
TI  - Usefulness of ultra-sensitive prostate-specific antigen following radical
      prostatectomy.
AB  - This study aimed to evaluate the usefulness of ultra-sensitive prostate-specific
      antigen (PSA) following radical prostatectomy (RP). Between September, 2003 and
      March, 2009, a total of 311 prostate cancer patients underwent antegrade RP;
      following the exclusion of 111 patients due to prior hormonal therapy, 200
      patients were finally included in this study. The results of the multivariate
      analysis identified RP Gleason score, extraprostatic extension, lymph node
      metastasis and PSA nadir as significant predictors of biochemical failure
      (P=0.0116, 0.0216, 0.0178 and <0.0001, respectively) and PSA nadir <0.008 ng/ml
      exhibited the highest hazard ratio (HR) [HR=26.34; 95% confidence interval (CI):
      7.34-104.69]. After a median follow-up period of 52.2 months, the biochemical
      failure-free rate in the PSA nadir <0.008 and >=0.008 ng/ml groups was 94.3 and
      58.8%, respectively, with a statistically significant difference according to the
      log-rank test (P<0.001). In the multivariate analysis, statistically significant
      differences were observed only in pathological nodel stage within the PSA nadir
      <0.008 ng/ml group (P=0.0107). For this reason, postoperative follow-up using
      ultra-sensitive PSA is considered to be of value, since the use of high
      sensitivity PSA to confirm a reduction to below postoperative measurement
      threshold value (PSA nadir <0.008 ng/ml) may avert administering unnecessary
      additional treatment, regardless of pathological reccurrence factors.

PMID- 25054058
TI  - Indirect comparisons of efficacy and safety between seven newer targeted agents
      for metastatic renal cell carcinoma: A network meta-analysis of randomised
      clinical trials.
AB  - This network meta-analysis aimed to compare the clinical efficacy and safety
      among 7 newer targeted agents for the treatment of metastatic renal cell
      carcinoma (mRCC). All randomised clinical trials (RCTs) of targeted therapeutic
      drugs for mRCC were included. The study selection, data extraction and quality
      assessment were performed independently by two reviewers. The analysis evaluated
      efficacy outcomes [improvement in the median progression-free survival (PFS)] and
      safety outcomes (number of withdrawals due to adverse events). The network
      analysis included direct and indirect analyses. The quality of the selected
      studies was assessed using the Grading of Recommendations, Assessment,
      Development and Evaluations (GRADE) method. We identified 7 articles eligible for
      inclusion in the study. The direct comparison of the targeted agents indicated
      better efficacy in terms of longer PFS, but worse safety (more withdrawals due to
      adverse events). The indirect analysis demonstrated that axitinib was
      significantly more effective compared to panzopanib; sunitinib was superior to
      sorafenib and temsirolimus regarding efficacy outcome, without any statistically
      significant difference in the safety outcome. The results of the quality
      assessment indicated moderate scores using the GRADE method. In conclusion, the
      result of this network analysis suggested that sunitinib and axitinib may be more
      clinically efficient and axitinib is associated with a lower risk of adverse
      events compared to sorafenib, pazopanib and temsirolimus.

PMID- 25054059
TI  - Treatment-interval associated effect of irradiation on locoregionally-relapsed
      ovarian cancer.
AB  - Recurrent ovarian cancer following chemotherapy is usually incurable,
      particularly when the tumor acquires a drug resistance. The present study aimed
      to define the effect of irradiation on locoregional recurrences and the impact of
      the factors on the efficacy. The study retrospectively reviewed the clinical
      records of 61 patients with epithelial ovarian cancer who received irradiation
      following repeated chemotherapy between 1997 and 2006. A positive-irradiation
      response was designated as complete response, partial response, minor response or
      no change (NC). Due to the possible synergistic effect of chemotherapy and
      irradiation, and the cross-resistance to chemotherapeutic drugs and radiation,
      the focus was on the treatment break between chemotherapy and radiation, and
      patients were classified into 3 categories: Category I, <=1 month; II, 1-6
      months; and III, >6 months. The effect of irradiation was analyzed in association
      with histology, treatment break, recurrent site, irradiation dose and
      chemosensitivity. The post-irradiation survival time was analyzed by the
      irradiation response and treatment category. The median biological-effective dose
      was 60.0 Gy (range, 15.6-72.0 Gy). The sites irradiated included nodal recurrence
      (36), abdominal (six) and pelvic cavity (five cases). Histologically, serous
      adenocarcinoma was the most common type of the disease (23 cases) compared to
      mucinous (four), endometrioid (three), and clear-cell types (six cases). The
      median survival times were 4.5 months in the radiation responders (13 cases) and
      15.3 months in the non-responders (37) (P=0.004). The positive-irradiation
      response was significantly associated with the treatment break (P=0.026) and
      chemosensitivity (P=0.007). In conclusion, irradiation for recurrent ovarian
      cancer produced an improved survival benefit when applied to chemoresponsive,
      locoregional-recurrent tumors immediately following chemotherapy.

PMID- 25054060
TI  - Quality of life in patients with esophageal cancer receiving definitive
      chemoradiotherapy or esophagectomy.
AB  - The aim of the present study was to assess the variation in the quality of life
      (QOL) of patients with esophageal cancer receiving definitive chemoradiotherapy
      or esophagectomy, and to explore the main factors that affects QOL. A total of
      102 patients with esophageal cancer receiving definitive chemoradiotherapy or
      esophagectomy were assessed using a QOL questionnaire, and a numeric score was
      calculated in each conceptual area and compared with reference data by a
      statistical method. With regards to the impacts on the QOL, the chemoradiotherapy
      had less of an impact compared with esophagectomy. The QOL declined following the
      two treatments, but was restored in a specific period of time. In the present
      study, the main factors that affected the QOL of patients included physical
      function, fatigue and pain. Definitive chemoradiotherapy is therefore superior to
      esophagectomy with regard to its effect on the QOL. The two treatments had an
      effect on the QOL of patients, but this effect was temporary and was resumed
      after a period of time.

PMID- 25054061
TI  - Metastatic bone tumors: Analysis of factors affecting prognosis and efficacy of
      CT and 18F-FDG PET-CT in identifying primary lesions.
AB  - We analyzed the prognostic factors in patients with metastatic bone tumors and
      evaluated the efficacy of different modalities in identifying the primary
      lesions. A total of 145 patients with bone metastases who attended the
      orthopaedic outpatient clinic were included in this study. The most frequent site
      of bone metastases was the spine. The primary tumor type was differently
      distributed between patients with a known primary tumor at the first visit and
      those with an unknown primary lesion. The number of breast cancer cases was
      statistically significantly lower in the primary-unknown group. However, the
      number of myeloma cases was significantly higher in the primary-unknown group.
      Survival was significantly lower in the skeletal-related events (SREs) compared
      to that in the non-SREs group. Furthermore, survival was significantly worse in
      patients with a performance status (PS) of >=2 compared to those with a PS of <=1
      and neurological complications occurred statistically more often in the group
      with worse PS (>=2). Survival rates were significantly lower in the non-spinal
      compared to those in the spinal metastatic group. Since the majority of breast
      cancer patients presented with metastasis in the spine, a breast cancer origin
      was a positive prognostic factor in patients with spinal metastases. Although
      there were no significant differences between computed tomography (CT) and 18F
      fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)-CT in
      detecting primary lesions, CT may be the first choice due to its feasibility. In
      conclusion, lung cancer, SREs and worse PS were adverse prognostic factors for
      patients with bone metastasis. In addition, CT scans may be more useful for
      determining the primary lesion of a bone metastasis compared to 18F-FDG PET-CT in
      a timelier manner.

PMID- 25054062
TI  - Nuclear artifacts in gastric endoscopic submucosal dissection specimens: A
      clinicopathological study.
AB  - To delineate the characteristics of nuclear artifacts associated with endoscopic
      submucosal dissection (ESD), we examined 97 gastric ESD specimens from 79
      patients. In 69 of the specimens (71%), multinucleated figures and/or atypical
      mitotic-like figures, including tripolar-like and bizarre spindles, were found in
      the peripheral portions close to the marking areas. These nuclear figures were
      mostly recognizable as artifacts, but were infrequently (13 specimens)
      accompanied by other nuclear alterations and/or architectural abnormalities,
      mimicking dysplasia. However, in the deep cut sections, the dysplastic
      characteristics tended to disappear and coagulative or degenerative findings
      became more prominent. These nuclear artifacts were not found in 69 age- and
      gender-matched control gastrectomy specimens without ESD. Multinucleated
      artifacts were associated with the size of the ESD specimens (P=0.003), frequency
      of marking (P<0.001) and a history of 'previous' marking 1-6 days prior to ESD
      (P<0.001); however, they were not associated with age, ESD procedure time, or
      'fresh' marking on the day of the ESD. Atypical mitosis-like characteristics were
      associated with a history of 'fresh' (P=0.007) as well as 'previous' (P=0.002)
      marking, but not with other variables. Dysplasia-like artifacts were associated
      with older age only (P=0.031). Follow-up data of all the patients with nuclear
      artifacts showed no aggressive behavior. Therefore, we concluded that these
      nuclear changes were ESD-related artifacts. Particularly in older patients, these
      changes may simulate dysplasia and must be distinguished from true dysplasia or
      neoplasia.

PMID- 25054063
TI  - The histone deacetylase inhibitor, LBH589, promotes the systemic cytokine and
      effector responses of adoptively transferred CD8+ T cells.
AB  - BACKGROUND: Histone deacetylase (HDAC) inhibitors are a class of agents that have
      potent antitumor activity with a reported ability to upregulate MHC and
      costimulatory molecule expression. We hypothesized that epigenetic
      pharmacological immunomodulation could sensitize tumors to immune mediated cell
      death with an adoptive T cell therapy. METHODS: The pan-HDAC inhibitor, LBH589,
      was combined with gp100 specific T cell immunotherapy in an in vivo B16 melanoma
      model and in an in vivo non-tumor bearing model. Tumor regression, tumor specific
      T cell function and phenotype, and serum cytokine levels were evaluated. RESULTS:
      Addition of LBH589 to an adoptive cell transfer therapy significantly decreased
      tumor burden while sustaining systemic pro-inflammatory levels. Furthermore,
      LBH589 was able to enhance gp100 specific T cell survival and significantly
      decrease T regulatory cell populations systemically and intratumorally. Even in
      the absence of tumor, LBH589 was able to enhance the proliferation, retention,
      and polyfunctional status of tumor specific T cells, suggesting its effects were
      T cell specific. In addition, LBH589 induced significantly higher levels of the
      IL-2 receptor (CD25) and the co-stimulatory molecule OX-40 in T cells.
      CONCLUSION: These results demonstrate that immunomodulation of adoptively
      transferred T cells by LBH589 provides a novel mechanism to increase in vivo
      antitumor efficacy of effector CD8 T cells.

PMID- 25054064
TI  - The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement
      of chemo-radiation therapy against murine glioblastoma.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is an enzyme with immune
      suppressive properties that is commonly exploited by tumors to evade immune
      destruction. Anti-tumor T cell responses can be initiated in solid tumors, but
      are immediately suppressed by compensatory upregulation of immunological
      checkpoints, including IDO. In addition to these known effects on the adaptive
      immune system, we previously showed widespread, T cell-dependent complement
      deposition during allogeneic fetal rejection upon maternal treatment with IDO
      blockade. We hypothesized that IDO protects glioblastoma from the full effects of
      chemo-radiation therapy by preventing vascular activation and complement
      dependent tumor destruction. METHODS: To test this hypothesis, we utilized a
      syngeneic orthotopic glioblastoma model in which GL261 glioblastoma tumor cells
      were stereotactically implanted into the right frontal lobes of syngeneic mice.
      These mice were treated with IDO-blocking drugs in combination with chemotherapy
      and radiation therapy. RESULTS: Pharmacologic inhibition of IDO synergized with
      chemo-radiation therapy to prolong survival in mice bearing intracranial
      glioblastoma tumors. We now show that pharmacologic or genetic inhibition of IDO
      allowed chemo-radiation to trigger widespread complement deposition at sites of
      tumor growth. Chemotherapy treatment alone resulted in collections of
      perivascular leukocytes within tumors, but no complement deposition. Adding IDO
      blockade led to upregulation of VCAM-1 on vascular endothelium within the tumor
      microenvironment, and further adding radiation in the presence of IDO-blockade
      led to widespread deposition of complement. Mice genetically deficient in
      complement component C3 lost all of the synergistic effects of IDO-blockade on
      chemo-radiation-induced survival. CONCLUSIONS: Together these findings identify a
      novel mechanistic link between IDO and complement, and implicate complement as a
      major downstream effector mechanism for the beneficial effect of IDO-blockade
      after chemo-radiation therapy. We speculate that this represents a fundamental
      pathway by which the tumor regulates intratumoral vascular activation and
      protects itself from immune-mediated tumor destruction.

PMID- 25054065
TI  - Aortic Stiffness Is Related to the Ischemic Brain Injury Biomarker N-Methyl-D
      aspartate Receptor Antibody Levels in Aortic Valve Replacement.
AB  - Background. Aortic stiffness changes the flow pattern of circulating blood
      causing microvascular damage to different end-organ tissues, such as brain cells.
      The relationship between aortic stiffness measured by pulse wave velocity (PWV)
      and serum ischemic brain injury biomarker N-methyl-D-aspartate receptor antibody
      (NR2Ab) levels in aortic valve replacement has not been assessed. Methods.
      Patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS) had
      their PWV and NR2Ab serum levels measured preoperatively. We analyzed PWV and
      NR2Ab in two ways: (1) as continuous variables using the actual value and (2) as
      dichotomous variables (PWV-norm and PWV-high groups) and (NR2Ab-low and NR2Ab
      high groups). Results. Fifty-six patients (71 +/- 8.4 years) were included in
      this study. The NR2Ab level (ng/mL) was significantly higher in the PWV-high
      group (n = 21) than in PWV-norm group (n = 35; median 1.8 +/- 1.2 versus 1.2 +/-
      0.7, resp., P = 0.003). NR2Ab level was positively associated with PWV and
      negatively associated with male gender. Multiple regression revealed PWV
      independently related to NR2Ab level, and PWV cut-off was associated with a 7.23
      times increase in the likelihood of having high NR2Ab (>1.8 ng/mL). Conclusion.
      Higher PWV in patients with surgical aortic stenosis is associated with higher
      levels of the ischemic brain biomarker NR2Ab. 

PMID- 25054066
TI  - Identification of potential herbal inhibitor of acetylcholinesterase associated
      Alzheimer's disorders using molecular docking and molecular dynamics simulation.
AB  - Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD
      associated disorders and are the only class of approved drugs by the Food and
      Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the
      target for many Alzheimer's dementia drugs which block the function of AChE but
      have some side effects. Therefore, in this paper, an attempt was made to
      elucidate cholinesterase inhibition potential of secondary metabolite from
      Cannabis plant which has negligible or no side effect. Molecular docking of 500
      herbal compounds, against AChE, was performed using Autodock 4.2 as per the
      standard protocols. Molecular dynamics simulations have also been carried out to
      check stability of binding complex in water for 1000 ps. Our molecular docking
      and simulation have predicted high binding affinity of secondary metabolite
      (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest
      that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of
      AChE, all of which fall under active site/subsite or binding pocket, might be
      critical for the inhibitory activity of AChE. This approach might be helpful to
      understand the selectivity of the given drug molecule in the treatment of
      Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6
      as a valuable small ligand molecule in treatment and prevention of AD associated
      disorders and further in vitro and in vivo investigations may prove its
      therapeutic potential. 

PMID- 25054067
TI  - Prevalence of Multiple Antibiotic Resistant Infections in Diabetic versus
      Nondiabetic Wounds.
AB  - Diabetes mellitus (DM) affects 23.6 million people in the USA and approximately
      20-25% of diabetic patients will develop foot ulceration during the course of
      their disease. Up to a quarter of these patients will develop infections that
      will necessitate amputation. Although many studies report that the rates of
      antibiotic resistant infections have increased dramatically in the DM population
      over the last decade, to our knowledge there have been no reports directly
      comparing the rates of antibiotic resistant infections in DM versus non-DM
      wounds. We performed a retrospective study comparing the wound infections of 41
      DM patients to those of 74 non-DM patients to test the hypothesis that infections
      with multidrug resistant organisms (MDRO) were more prevalent in the DM
      population. We found that 63.4% of DM and 50% of non-DM patients had MDRO
      infections, which was not statistically different. However, 61% of the DM
      patients had Pseudomonas infections compared to only 18.9% of non-DM patients.
      Furthermore, DM patients had significantly more coinfections with both
      Pseudomonas and Staphylococcus aureus. Though our initial hypothesis was
      incorrect, we demonstrated a significant correlation between Pseudomonas and
      Pseudomonas/S. aureus coinfections within DM wounds. 

PMID- 25054068
TI  - Expanding prevertebral soft tissue swelling subsequent to a motor vehicle
      collision.
AB  - Cervical acceleration/deceleration or whiplash injuries are a common cause of
      cervical spine trauma. Cervical acceleration/deceleration can result in vertebral
      fractures, subluxations, and ligamentous and other soft tissue injuries. Severe
      injuries are often evidenced by increased prevertebral swelling on lateral X-ray.
      Assessment of the prevertebral space on lateral cervical spine films is an
      essential component for identifying potential traumatic neck injuries. We
      describe a case in which an 84-year-old man on coumadin presented to the
      emergency department after a low-impact motor vehicle crash. The patient
      initially complained of neck and shoulder pain which subsequently progressed to
      hoarseness, dysphagia, and dyspnea. Imaging studies revealed significant
      prevertebral tissue swelling with anterior compression of his airway that
      required airway stabilization via awake fiber-optic intubation and reversal of
      his anticoagulation therapy. 

PMID- 25054069
TI  - A case report of typhoidal acute acalculous cholecystitis.
AB  - Introduction. Acalculous cholecystitis in the setting of typhoid fever in adults
      is an infrequent clinical encounter, reported sparsely in the literature. In this
      case report we review the presentation and management of enteric fever involving
      the biliary system and consider the literature surrounding this topic. The aim of
      this case report is to alert clinicians to the potential diagnosis of
      extraintestinal complications in the setting of typhoid fever in the returned
      traveller, requiring surgical intervention. Presentation of Case. We report the
      case of a 23-year-old woman with acalculous cholecystitis secondary to Salmonella
      Typhi. Discussion. There is scarce evidence surrounding the optimal treatment and
      prognosis of typhoidal acalculous cholecystitis. In the current case, surgical
      invention was favoured due to failure of medical management. Conclusion. Clinical
      judgement dictated surgical intervention in this case of typhoidal acute
      acalculous cholecystitis, and cholecystectomy was safely performed. 

PMID- 25054070
TI  - Severe Hypocalcemia due to Denosumab in Metastatic Prostate Cancer.
AB  - Denosumab is a monoclonal antibody used for prevention of skeletal-related events
      (SREs) in patients with bone metastases from solid tumors. Hypocalcemia is a rare
      and dangerous side effect of the drug Denosumab. We present a case of a patient
      with metastatic prostate cancer who developed severe hypocalcemia after the
      administration of the drug. The patient's vitamin D levels were low when checked
      after administration of the drug, which likely predisposed him to the development
      of hypocalcemia. He was placed on high doses of oral and intravenous (IV) calcium
      and vitamin D without any appreciable response in the serum calcium level. His
      ionized calcium remained below 0.71 mmol/L despite very high doses of oral and IV
      calcium supplements. During the hospital course, he developed hydronephrosis from
      the spread of a tumor and did not want to undergo percutaneous nephrostomy tube
      placement; therefore, it was decided to dialyse him for acute renal failure and
      to correct his hypocalcemia. Checking calcium and vitamin D levels prior to the
      administration of Denosumab is vital in preventing hypocalcemia. If hypocalcemia
      is severe and not responsive to high doses of vitamin D, oral and IV calcium,
      then hemodialysis with a high calcium bath can correct this electrolyte
      abnormality. 

PMID- 25054071
TI  - Management of Gamma-Butyrolactone Dependence with Assisted Self-Administration of
      GBL.
AB  - Gamma-hydroxybutyric acid (GHB) and its liquid precursor gamma-butyrolactone
      (GBL) have become increasingly popular beyond the clubbing culture resulting in
      daily consumption and dependence in the broader population. This case report
      illustrates the challenges of managing GHB-withdrawal and a possibly superior
      future approach of its management by titration and tapering of the addictive
      agent. 

PMID- 25054072
TI  - Spontaneous resolution of subretinal hemorrhage secondary to choroidal osteoma
      unassociated with choroidal neovascularization.
AB  - Choroidal osteoma is a rare benign intraocular tumor composed of calcification
      throughout the choroid. Various treatment modalities are available according to
      location of the tumor and the cause of the visual distortion. We report herein a
      30-year-old male who was referred to our hospital with acute blurred vision as a
      result of the subretinal hemorrhage from choroidal osteoma. We ruled out the
      presence of CNV and observation was preferred and we prevented unnecessary
      treatment attempts as spontaneous recovery is the easiest and safest way. 

PMID- 25054073
TI  - Trevor's Disease: A Literature Review regarding Classification, Treatment, and
      Prognosis apropos of a Case.
AB  - Background. Dysplasia epiphysealis hemimelica (DEH) is rare and its main
      characteristic is osteochondromas of the epiphysis of long bones. Methods. We
      report a case of DEH of the ankle in an 8-year-old boy that was resected in 2005.
      Additionally we collect all the reported cases of DEH. The literature is reviewed
      regarding the treatment, prognosis, long term function, and patterns and areas
      affected by DEH. Results. In our case no complications were noted and our patient
      remains asymptomatic. Reviewing the literature we found that 73 authors have
      reported 144 cases from 1926 to 2013. We propose and describe a new
      classification that correlates with prognosis. According to our classification
      DEH is classified as types 1 with single lower limb involvement, 2 with multiple
      lower limb, 3 with single upper limb, 4 with multiple upper limb, 5 with upper
      and lower limb, and 6 with spine. Conclusions. All single lesions should be
      followed up and if indicated a whole body nuclear bone scan can be useful in
      identifying the existence of multiple affected joints. Type 1 lesions have better
      prognosis than 2 and have less chances of developing OA even if not resected.
      Resection, even if partial, can be a successful treatment for DEH. 

PMID- 25054075
TI  - Rapid discrimination of the geographical origins of an oolong tea (anxi
      tieguanyin) by near-infrared spectroscopy and partial least squares discriminant
      analysis.
AB  - This paper focuses on a rapid and nondestructive way to discriminate the
      geographical origin of Anxi-Tieguanyin tea by near-infrared (NIR) spectroscopy
      and chemometrics. 450 representative samples were collected from Anxi County, the
      original producing area of Tieguanyin tea, and another 120 Tieguanyin samples
      with similar appearance were collected from unprotected producing areas in China.
      All these samples were measured by NIR. The Stahel-Donoho estimates (SDE)
      outlyingness diagnosis was used to remove the outliers. Partial least squares
      discriminant analysis (PLSDA) was performed to develop a classification model and
      predict the authenticity of unknown objects. To improve the sensitivity and
      specificity of classification, the raw data was preprocessed to reduce unwanted
      spectral variations by standard normal variate (SNV) transformation, taking
      second-order derivatives (D2) spectra, and smoothing. As the best model, the
      sensitivity and specificity reached 0.931 and 1.000 with SNV spectra. Combination
      of NIR spectrometry and statistical model selection can provide an effective and
      rapid method to discriminate the geographical producing area of Anxi-Tieguanyin. 

PMID- 25054074
TI  - Limited Applicability of GW9662 to Elucidate PPARgamma-Mediated Fatty Acid
      Effects in Primary Human T-Helper Cells.
AB  - Synthetic antagonists of the nuclear receptor PPARgamma such as GW9662 are widely
      used to elucidate receptor-mediated ligand effects. In addition and complementary
      to recent work, we examined whether GW9662 is suitable to serve for mechanistic
      investigation in T-helper cells. Human peripheral blood mononuclear cells (PBMC)
      were preincubated with increasing concentrations of GW9662 (0, 0.4, 2, and 10
      MUmol/L) 30 min before adding the c9,t11-isomer of conjugated linoleic acid
      (c9,t11-CLA) as representative of PPARgamma-activating fatty acids with
      immunomodulatory properties. Corresponding cultures were incubated with GW9662 in
      the absence of the fatty acid. After 19 h, cells were mitogen stimulated for
      further 5 h. Subsequently, intracellular IL-2 was measured in CD3(+)CD4(+)
      lymphocytes by means of flow cytometry. 100 MUmol/L c9,t11-CLA reduced the number
      of T-helper cells expressing IL-2 by 68%. GW9662 failed to abrogate this fatty
      acid effect, likely due to the fact that the compound exerted an own inhibitory
      effect on IL-2 production. Moreover, GW9662 dose-dependently induced cell death
      in human leukocytes. These results suggest that application of GW9662 is not
      conducive in this experimental setting. 

PMID- 25054076
TI  - Patent foramen ovale and closure technique with the amplatzer occluder.
AB  - Proof that percutaneous closure of the patent foramen ovale (PFO) is superior to
      medical treatment is still incomplete. Paradoxical embolism is a rare event
      occurring over decades rather than years. None of the 4 randomized trials
      published carried enough patients or was followed up for long enough to reach
      superiority endpoints. All data, however, point to a benefit of PFO closure. Free
      wall erosion (exceedingly rare) and triggering of atrial fibrillation (in about
      1% of patients) are the only noteworthy complications. They are outweighed by the
      supposedly prevented events of paradoxical embolisms, such as stroke, transient
      ischemic attacks, myocardial infarctions, or other systemic embolisms. Medical
      treatment with perhaps the exception of lifelong oral anticoagulation provides
      less protection. During a 10-year follow-up of a comparative study the annual
      mortality was significantly lower in the patients with PFO closure (0.4%) than in
      those with medical treatment (1.1%, P < 0.03). PFO closure can be accomplished in
      less than 1 hour with immediate resumption of physical activity. It represents
      thus a kind of mechanical vaccination. 

PMID- 25054078
TI  - Staphylococcus aureus: Screening for Nasal Carriers in a Community Setting with
      Special Reference to MRSA.
AB  - Introduction. Emergence of MRSA infections among previously healthy persons in
      community settings (without exposure to health care facilities) has been noted
      recently. MRSA infections are now classified as health care-associated MRSA (HA
      MRSA) and community-associated MRSA (CA-MRSA) infections. Its colonization is an
      important risk factor for subsequent MRSA infection. Aims and Objectives. The aim
      was to screen patients and health care workers for staphylococcal carriage,
      identify risk factors for MRSA colonization, and determine the sensitivity
      pattern. Materials and Methods. A total of 200 subjects were screened for nasal
      carriage after obtaining verbal consent. These were both healthy subjects
      attending various outpatient departments and health care workers. Specimens were
      collected from the anterior nares using premoistened sterile cotton swabs and
      inoculated onto blood agar and mannitol salt agar and incubated at 37 degrees C
      for 24-48 h. Results. Staphylococcus aureus colonisation was found to be 12% (n =
      24). MRSA was identified in 5% (n = 10) which represents 41.66% of SA. A total of
      10 strains of MRSA were isolated from 200 subjects, giving an overall positivity
      rate of 5%. Discussion. Staphylococcal colonization was found to be 12% (MRSA
      5%). Fluoroquinolone resistance was remarkable whereas all strains were sensitive
      to vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin. 

PMID- 25054079
TI  - Caffeine's Attenuation of Cocaine-Induced Dopamine Release by Inhibition of
      Adenosine.
AB  - Background: It is well known that the reinforcing properties of cocaine addiction
      are caused by the sharp increase of dopamine (DA) in the reward areas of the
      brain. However, other mechanisms have been speculated to contribute to the
      increase. Adenosine is one system that is associated with the sleep-wake cycle
      and is most important in regulating neuronal activity. Thus, more and more
      evidence is pointing to its involvement in regulating DA release. The current
      study set out to examine the role of adenosine in cocaine-induced DA release.
      Methods: Increasing doses of cocaine, caffeine, and their combination, as well
      as, 8-cyclopentyltheophylline (CPT), an adenosine A1 antagonist (alone and in
      combination with cocaine) were used to denote a response curve. A novel
      biosensor, the BRODERICK PROBE(r) was implanted in the nucleus accumbens to image
      the drug-induced surge of DA release in vivo, in the freely moving animal in real
      time. Results: Combinations of cocaine and caffeine were observed to block the
      increased release of DA moderately after administration of the low dose (2.5
      mg/kg cocaine and 12.5 mg/kg caffeine) and dramatically after administration of
      the high dose (10 mg/kg cocaine and 50 mg/kg caffeine), suggesting
      neuroprotection. Similarly, CPT and cocaine showed a decreased DA surge when
      administered in combination. Thus, the low and high dose of a nonselective
      adenosine antagonist, caffeine, and a moderate dose of a selective adenosine
      antagonist, CPT, protected against the cocaine-induced DA release. Conclusions:
      These results show a significant interaction between adenosine and DA release and
      suggest therapeutic options for cocaine addiction and disorders associated with
      DA dysfunction.

PMID- 25054077
TI  - Utilizing cytokines to function-enable human NK cells for the immunotherapy of
      cancer.
AB  - Natural killer (NK) cells are innate lymphoid cells important for host defense
      against pathogens and mediate antitumor immunity. Cytokine receptors transduce
      important signals that regulate proliferation, survival, activation status, and
      trigger effector functions. Here, we review the roles of major cytokines that
      regulate human NK cell development, survival, and function, including IL-2, IL
      12, IL-15, IL-18, and IL-21, and their translation to the clinic as immunotherapy
      agents. We highlight a recent development in NK cell biology, the identification
      of innate NK cell memory, and focus on cytokine-induced memory-like (CIML) NK
      cells that result from a brief, combined activation with IL-12, IL-15, and IL-18.
      This activation results in long lived NK cells that exhibit enhanced
      functionality when they encounter a secondary stimulation and provides a new
      approach to enable NK cells for enhanced responsiveness to infection and cancer.
      An improved understanding of the cellular and molecular aspects of cytokine
      cytokine receptor signals has led to a resurgence of interest in the clinical use
      of cytokines that sustain and/or activate NK cell antitumor potential. In the
      future, such strategies will be combined with negative regulatory signal blockade
      and enhanced recognition to comprehensively enhance NK cells for immunotherapy. 

PMID- 25054080
TI  - Subjective State, Blood Pressure, and Behavioral Control Changes Produced by an
      "Energy Shot"
AB  - Background: Energy drinks and energy shots are popular consumer beverages that
      are advertised to increase feelings of alertness. Typically, these products
      include high levels of caffeine, a mild psychostimulant drug. The scientific
      evidence demonstrating the specific benefits of energy products to users in terms
      of subjective state and objective performance is surprisingly lacking. Moreover,
      there are rising health concerns associated with the use of these products.
      Therefore, the purpose of this study was to investigate the acute effects of a
      popular energy shot (5-Hour Energy(r)) on subjective and objective measures that
      were assessed hourly for 6 hours following consumption. Methods: Participants
      (n=14) completed a three-session study where they received the energy shot, a
      placebo control, and no drink. Following dose administration, participants
      completed subjective Profile of Mood States ratings hourly for 6 hours.
      Participants also repeatedly completed a behavioral control task (the cued go/no
      go task) and provided blood pressure and pulse rate readings at each hour.
      Results: Consumption of the energy shot did improve subjective state, as measured
      by increased ratings of vigor and decreased ratings of fatigue. However, the
      energy shot did not alter objective performance, which worsened over time.
      Importantly, the energy shot elevated both systolic and diastolic blood pressure.
      Conclusions: Consumption of one energy shot may only result in modest benefits to
      subjective state. Individuals with preexisting hypertension or other medical
      conditions should be cautious about using these new consumer products.

PMID- 25054081
TI  - Burgeoning evidence indicates that microRNAs were initially formed from
      transposable element sequences.
AB  - MicroRNAs (miRNAs) constitute a recently discovered class of noncoding RNAs that
      play key roles in the regulation of gene expression. Despite being only ~20
      nucleotides in length, these highly versatile molecules have been shown to play
      pivotal roles in development, basic cellular metabolism, apoptosis, and disease.
      While over 24,000 miRNAs have been characterized since they were first isolated
      in mammals in 2001, the functions of the majority of these miRNAs remain largely
      undescribed. That said, many now suggest that characterization of the
      relationships between miRNAs and transposable elements (TEs) can help elucidate
      miRNA functionality. Strikingly, over 20 publications have now reported the
      initial formation of thousands of miRNA loci from TE sequences. In this review we
      chronicle the findings of these reports, discuss the evolution of the field along
      with future directions, and examine how this information can be used to ascertain
      insights into miRNA transcriptional regulation and how it can be exploited to
      facilitate miRNA target prediction.

PMID- 25054082
TI  - Expression and detection of LINE-1 ORF-encoded proteins.
AB  - LINE-1 (L1) elements are endogenous retrotransposons active in mammalian genomes.
      The L1 RNA is bicistronic, encoding two non-overlapping open reading frames, ORF1
      and ORF2, whose protein products (ORF1p and ORF2p) bind the L1 RNA to form a
      ribonucleoprotein (RNP) complex that is presumed to be a critical
      retrotransposition intermediate. However, ORF2p is expressed at a significantly
      lower level than ORF1p; these differences are thought to be controlled at the
      level of translation, due to a low frequency ribosome reinitiation mechanism
      controlling ORF2 expression. As a result, while ORF1p is readily detectable,
      ORF2p has previously been very challenging to detect in vitro and in vivo. To
      address this, we recently tested several epitope tags fused to the N- or C
      termini of the ORF proteins in an effort to enable robust detection and affinity
      purification from native (L1RP) and synthetic (ORFeus-Hs) L1 constructs. An
      analysis of tagged RNPs from both L1RP and ORFeus-Hs showed similar host-cell
      derived protein interactors. Our observations also revealed that the tag
      sequences affected the retrotransposition competency of native and synthetic L1s
      differently although they encode identical ORF proteins. Unexpectedly, we
      observed apparently stochastic expression of ORF2p within seemingly homogenous L1
      expressing cell populations.

PMID- 25054083
TI  - The taming of the shrew: Regulation of a catalytically active domesticated
      transposase.
AB  - Transposons are mobile genetic elements that can be harmful for the host when
      mobilized. However, they are also genomic reservoirs for novel genes that can be
      evolutionarily beneficial. There are many examples of domesticated transposases,
      which play important roles in the hosts. In most cases domesticated transposases
      have lost their endonuclease activities and the hosts utilize their DNA-binding
      properties. However, some other domesticated transposases perform endonuclease
      activities for host biological processes. Because such a catalytically active
      transposase is potentially harmful for the integrity of the host genome, its
      activity should be tightly regulated. The catalytically active domesticated
      piggyBac transposase Tpb2p catalyzes programmed DNA elimination in the ciliate
      Tetrahymena. Here, we discuss the regulatory mechanism that prevents unintended
      DNA cleavage by Tpb2p and compare it to another well-studied catalytically active
      domesticated transposase, the RAG recombinase in V(D)J recombination. The
      regulatory mechanisms involve the temporarily regulated expression of the
      transposases, the target sequence preference of the endonuclease, and the
      recruitment of the transposases to locally restricted chromatin environments.

PMID- 25054084
TI  - An intronic open reading frame was released from one of group II introns in the
      mitochondrial genome of the haptophyte Chrysochromulina sp. NIES-1333.
AB  - Mitochondrial (mt) genome sequences, which often bear introns, have been sampled
      from phylogenetically diverse eukaryotes. Thus, we can anticipate novel insights
      into intron evolution from previously unstudied mt genomes. We here investigated
      the origins and evolution of three introns in the mt genome of the haptophyte
      Chrysochromulina sp. NIES-1333, which was sequenced completely in this study. All
      the three introns were characterized as group II, on the basis of predicted
      secondary structure, and the conserved sequence motifs at the 5' and 3' termini.
      Our comparative studies on diverse mt genomes prompt us to propose that the
      Chrysochromulina mt genome laterally acquired the introns from mt genomes in
      distantly related eukaryotes. Many group II introns harbor intronic open reading
      frames for the proteins (intron-encoded proteins or IEPs), which likely
      facilitate the splicing of their host introns. However, we propose that a "free
      standing," IEP-like protein, which is not encoded within any introns in the
      Chrysochromulina mt genome, is involved in the splicing of the first cox1 intron
      that lacks any open reading frames.

PMID- 25054086
TI  - Nobel Prize for Cellular Logistics!

PMID- 25054085
TI  - Harnessing mobile genetic elements to explore gene regulation.
AB  - Sequences that regulate expression of a gene in cis but are located at large
      distances along the DNA from the gene, as found with most developmentally
      regulated genes in higher vertebrates, are difficult to identify if those
      sequences are not conserved across species. Mutating suspected gene-regulatory
      sequences to alter expression then becomes a hit-or-miss affair. The relaxed
      specificity of transposon insertions offers an opportunity to develop alternate
      strategies, to scan in an unbiased manner, pieces of chromosomal DNA cloned in
      BACs for transcription enhancing elements. This article illustrates how
      insertions of Tn10 with enhancer-traps into BAC DNA containing the gene, and its
      germ-line expression in zebrafish, have identified distal regulatory elements
      functionally. Transposition of Tn10 first introduces the enhancer-trap with a
      loxP site randomly into BAC DNA. Cre-recombination between the inserted loxP and
      the loxP endogenous to a BAC-end positions the enhancer-trap to the newly created
      truncated end of BAC DNA. The procedure generates a library of integration-ready
      enhancer-trap BACs with progressive truncations from an end in a single
      experiment. Individual enhancer-trap BACs from the library can be evaluated
      functionally in zebrafish or mice. Furthermore, the ability to readily alter
      sequences in a small transposon plasmid containing a regulatory domain of the
      gene allows re-introduction of altered parts of a BAC back into itself. It serves
      as a useful strategy to functionally dissect multiple discontinuous regulatory
      domains of a gene quickly. These methodologies have been successfully used in
      identifying novel regulatory domains of the Amyloid Precursor Protein (appb) gene
      in zebrafish, and provided important clues for regulation of the gene in humans.

PMID- 25054087
TI  - Anticancer Tc9 cells: Long-lived tumor-killing T cells for adoptive therapy.
AB  - IL-9-producing cytotoxic T (Tc9) cells represent a unique CD8+ T-cell subset.
      These long-lived immune cells possess the capacity to acquire effector function
      and home to tumor tissues after adoptive transfer. IL-9 is indispensable for Tc9
      mediated superior antitumor response. These findings are highly significant and
      crucial to achieve advances in T cell-based adoptive therapies.

PMID- 25054088
TI  - Myeloid-derived suppressor cells link inflammation to cancer.
AB  - Our recent work has provided the first evidence that MDSCs promote chronic
      colonic inflammation and colitis-associated carcinogenesis. Our findings not only
      reveal a novel function of MDSCs in connecting inflammation to cancer, but also
      provide a rationale for developing effective therapeutic strategies to subvert
      inflammation- and tumor-induced immunosuppression.

PMID- 25054089
TI  - The hedgehog's trick for escaping immunosurveillance: The molecular mechanisms
      driving myeloid-derived suppressor cell recruitment in hedgehog signaling
      dependent tumors.
AB  - Myeloid-derived suppressor cells (MDSCs) are an important means by which tumor
      cells evade immunosurveillance. Here, we set out to determine how MDSCs are
      recruited to tumors in genetically engineered mouse cancer models. Expression of
      oncogenic and constitutively active SmoM2, a key hedgehog-signaling regulatory
      protein, revealed that MDSC recruitment to the tumor microenvironment is mediated
      by the CCL2/CCR2 axis in a TGFbeta dependent fashion.

PMID- 25054090
TI  - SHP-1 and IL-1alpha conspire to provoke neutrophilic dermatoses.
AB  - Neutrophilic dermatoses are a spectrum of autoinflammatory skin disorders that
      are characterized by extensive infiltration of neutrophils into the epidermis and
      dermis. The underlining biological pathways that are responsible for this
      heterogeneous group of cutaneous diseases have remained elusive. However, recent
      work from our laboratory and other groups has shown that missense mutations in
      Ptpn6, which encodes for the non-receptor protein tyrosine phosphatase Src
      homology region 2 (SH2) domain-containing phosphatase-1 (SHP-1), results in a
      skin disease with many of the major histopathological and clinical features that
      encompass neutrophilic dermatoses in humans. In particular, we found that loss-of
      function mutation in Ptpn6 results in unremitting footpad swelling, suppurative
      inflammation, and neutrophilia. Dysregulated wound healing responses were
      discovered to contribute to chronic inflammatory skin disease in SHP-1 defective
      mice and genetic abrogation of interleukin-1 receptor (IL-1R) protected mice from
      cutaneous inflammation, suggesting that IL-1-mediated events potentiate disease.
      Surprisingly, inflammasome activation and IL-1beta-mediated events were
      dispensable for Ptpn6(spin) -mediated footpad disease. Instead, RIP1-mediated
      regulation of IL-1alpha was identified to be the major driver of inflammation and
      tissue damage. 

PMID- 25054091
TI  - Roberts syndrome: A deficit in acetylated cohesin leads to nucleolar dysfunction.
AB  - All living organisms must go through cycles of replicating their genetic
      information and then dividing the copies between two new cells. This cyclical
      process, in cells from bacteria and human alike, requires a protein complex known
      as cohesin. Cohesin is a structural maintenance of chromosomes (SMC) complex.
      While bacteria have one form of this complex, yeast have several SMC complexes,
      and humans have at least a dozen cohesin complexes alone. Therefore the ancient
      structure and function of SMC complexes has been both conserved and specialized
      over the course of evolution. These complexes play roles in replication, repair,
      organization, and segregation of the genome. Mutations in the genes that encode
      cohesin and its regulatory factors are associated with developmental disorders
      such as Roberts syndrome, Cornelia de Lange syndrome, and cancer. In this review,
      we focus on how acetylation of cohesin contributes to its function. In Roberts
      syndrome, the lack of cohesin acetylation contributes to nucleolar defects and
      translational inhibition. An understanding of basic SMC complex function will be
      essential to unraveling the molecular etiology of human diseases associated with
      defective SMC function. 

PMID- 25054092
TI  - SETX sumoylation: A link between DNA damage and RNA surveillance disrupted in
      AOA2.
AB  - Senataxin (SETX) is a putative RNA:DNA helicase that is mutated in two distinct
      juvenile neurological disorders, AOA2 and ALS4. SETX is involved in the response
      to oxidative stress and is suggested to resolve R loops formed at transcription
      termination sites or at sites of collisions between the transcription and
      replication machineries. R loops are hybrids between RNA and DNA that are
      believed to lead to DNA damage and genomic instability. We discovered that Rrp45,
      a core component of the exosome, is a SETX-interacting protein and that the
      interaction depends on modification of SETX by sumoylation. Importantly, we
      showed that AOA2 but not ALS4 mutations prevented both SETX sumoylation and the
      Rrp45 interaction. We also found that upon replication stress induction, SETX and
      Rrp45 co-localize in nuclear foci that constitute sites of R-loop formation
      generated by transcription and replication machinery collisions. We suggest that
      SETX links transcription, DNA damage and RNA surveillance, and discuss here how
      this link can be relevant to AOA2 disease. 

PMID- 25054093
TI  - A Drosophila screen identifies neurofibromatosis-1 genetic modifiers involved in
      systemic and synaptic growth.
AB  - Neurofibromatosis type 1 (NF1) is caused by loss of a negative regulator of Ras
      oncoproteins. Unknown genetic modifiers have been implicated in NF1's
      characteristic variability. Drosophila melanogaster dNf1 phenotypes include
      cognitive deficits and reduced growth, both of which resemble human symptoms. We
      recently reported results of a screen for dominant modifiers of dNf1 growth.
      Suppressors include the dAlk tyrosine kinase and its activating ligand, two other
      genes involved in Ras/ERK signal transduction, the synaptic scaffold Dap160 and
      the CCKLR-17D1 drosulfakinin receptor. Additional modifiers include several genes
      involved in cAMP/PKA signaling. Providing mechanistic insights, dAlk, jeb, and
      CCKLR-17D1 also suppress a dNf1 synaptic overgrowth defect, and increasing
      cAMP/PKA signaling in the neuroendocrine ring gland rescued the dNf1 growth
      deficiency. Finally, among the several suppressors identified in our screen, we
      specifically implicate ALK as a potential therapeutic target by showing that NF1
      regulated ALK/RAS/ERK signaling is conserved in human cells. 

PMID- 25054094
TI  - Using antisense technology to develop a novel therapy for alpha-1 antitrypsin
      deficient (AATD) liver disease and to model AATD lung disease.
AB  - Alpha-1 antitrypsin (AAT) is a serum protease inhibitor that belongs to the
      serpin superfamily. Mutations in AAT are associated with alpha-1 antitrypsin
      deficiency (AATD), a rare genetic disease with two distinct manifestations: AATD
      lung disease and AATD liver disease. AATD lung disease is caused by loss-of
      function of AAT and can be treated with plasma-derived AAT. AATD liver disease is
      due to the aggregation and retention of mutant AAT protein in the liver; the only
      treatment available for AATD liver disease is liver transplantation. Here we
      demonstrate that antisense oligonucleotides (ASOs) targeting human AAT
      efficiently reduce levels of both short and long human AAT transcript in vitro
      and in transgenic mice, providing a novel therapy for AATD liver disease. In
      addition, ASO-mediated depletion of mouse AAT may offer a useful animal model for
      the investigation of AATD lung disease. 

PMID- 25054095
TI  - The challenge in translating basic research discoveries to treatment of
      Huntington disease.
AB  - Huntington disease is a rare neurodegenerative disease resulting from insertion
      and/or expansion of a polyglutamine repeats close to the N-terminal of the
      huntingtin protein. Although unequivocal genetic tests have been available for
      about 20 years, current pharmacological treatments do not prevent or slow down
      disease progression. Recent basic research identified potential novel drug
      targets for the treatment of Huntington disease. However, there are clear
      challenges in translating these discoveries into treatment strategies for these
      patients. The following is a brief discussion of these challenges using our
      recent experience as an example. 

PMID- 25054096
TI  - Epistatic interactions between Chd7 and Fgf8 during cerebellar development:
      Implications for CHARGE syndrome.
AB  - CHARGE syndrome is a rare, autosomal dominant condition caused by mutations in
      the CHD7 gene. Although central nervous system defects have been reported, the
      detailed description and analysis of these anomalies in CHARGE syndrome patients
      lag far behind the description of other, more easily observed defects. We
      recently described cerebellar abnormalities in CHARGE syndrome patients and used
      mouse models to identify the underlying causes. Our studies identified altered
      expression of the homeobox genes Otx2 and Gbx2 in the developing neural tube of
      Chd7(-/-) embryos. Furthermore, we showed that the expression of Fgf8 is
      sensitive to Chd7 gene dosage and demonstrated an epistatic relationship between
      these genes during cerebellar vermis development. These findings provided, for
      the first time, an example of cerebellar vermis hypoplasia in a human syndrome
      that can be linked to deregulated FGF signaling. I discuss some of these
      observations and their implications for CHARGE syndrome. 

PMID- 25054097
TI  - Pulling complexes out of complex diseases: Spinocerebellar Ataxia 7.
AB  - Spinocerebellar ataxia 7 (SCA7) is an incurable disease caused by expansion of
      CAG trinucleotide sequences within the Ataxin-7 gene. This elongated CAG tract
      results in an Ataxin-7 protein bearing an expanded polyglutamine (PolyQ) repeat.
      SCA7 disease is characterized by progressive neural and retinal degeneration
      leading to ataxia and blindness. Evidence gathered from investigating SCA7 and
      other PolyQ diseases strongly suggest that misregulation of gene expression
      contributes to neurodegeneration. In fact, Ataxin-7 is a subunit of the essential
      Spt-Ada-Gcn5-Acetltransferase (SAGA) chromatin modifying complex that regulates
      expression of a large number of genes. Here we discuss recent insights into
      Ataxin-7 function and, considering these findings, propose a model for how
      polyglutamine expansion of Ataxin-7 may affect Ataxin-7 function to alter
      chromatin modifications and gene expression. 

PMID- 25054098
TI  - Sarcomatoid malignant mesothelioma presenting with intramedullary spinal cord
      metastasis: a case report and literature review.
AB  - Study Design Case report. Objective Malignant mesothelioma (MM) is an uncommon
      tumor of the pleural epithelium with a predilection for local spread into
      adjacent tissues. The sarcomatoid type accounts for ~10% of MM cases and is
      associated with poorer survival than the epithelioid, desmoplastic, and biphasic
      types. MM commonly presents with involvement of the vertebral body or epidural
      space. However, intradural spinal extension of MM is extremely rare. Only eight
      cases of intradural spinal extension have been reported. We report this rare case
      and discuss the clinical manifestations of intradural spinal extension of MM with
      literature review. Methods This report describes the case of a 62-year-old man
      with Brown-Sequard syndrome and radiculopathy of the left C5 nerve root detected
      during treatment for pleural sarcomatoid MM. Magnetic resonance imaging (MRI)
      showed an intramedullary lesion at the C3 level and a small nodule at the left C5
      nerve root with cervical canal stenosis. Results The patient underwent surgery,
      and intramedullary metastasis of sarcomatoid MM was diagnosed. Subsequently,
      radiotherapy was administered, resulting in temporary improvement of the
      patient's condition. Thereafter, his condition gradually deteriorated, and follow
      up MRI showed a more extensive residual C3 intramedullary lesion. Thus, a second
      surgery was performed after chemotherapy, but the patient died 5 months after the
      initial diagnosis. Conclusion We present this rare case, and emphasize
      intramedullary spinal cord metastasis of MM as differential diagnosis in primary
      cord lesion. 

PMID- 25054099
TI  - Kinetic magnetic resonance imaging of the cervical spine: a review of the
      literature.
AB  - Study Design Literature review. Objective The purpose of this study is to compile
      and review the body of literature related to kinetic magnetic resonance imaging
      (kMRI) of the cervical spine. Methods A review of literature related to kMRI was
      performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses) guidelines. Results We included 16 prospective and retrospective
      studies of symptomatic and asymptomatic patients who underwent kMRI of the
      cervical spine. Conclusions Data suggest that kMRI is able to provide meaningful
      information regarding changes in the cervical spine in both normal and pathologic
      segments. A prospective study comparing magnetic resonance imaging and kMRI is
      needed to confirm clinically utility of this technology. 

PMID- 25054100
TI  - Incorporating the Spine Instability Neoplastic Score into a Treatment Strategy
      for Spinal Metastasis: LMNOP.
AB  - Study Design Review. Objective To describe a decision framework that incorporates
      key factors to be considered for optimal treatment of spinal metastasis and
      highlight how this system incorporates the Spinal Instability Neoplastic Score
      (SINS). Methods We describe how treatment options for spinal metastasis have
      broadened in recent years with advancements in stereotactic radiosurgery,
      vertebral augmentation, and other minimally invasive techniques. We discuss
      classification-based approaches to the treatment of spinal metastasis versus
      principles-based approaches and argue that the latter may be more appropriate for
      optimal patient informed consent. Case examples are provided. Results Scoring
      systems at best produce an estimate of life expectancy but fall short in
      incorporating all of the relevant factors that determine which treatment(s) may
      be indicated. We advocate a principle-based decision framework called LMNOP that
      considers: (L) location of disease with respect to the anterior and/or posterior
      columns of the spine and number of spinal levels involved (contiguous or non
      contiguous); (M) mechanical instability as graded by SINS; (N) neurology
      (symptomatic epidural spinal cord compression); (O) oncology (histopathologic
      diagnosis), particularly with respect to radiosensitivity; and (P) patient
      fitness, patient wishes, prognosis (which is mostly dependent on tumor type), and
      response to prior therapy. Conclusions LMNOP is the first systematic approach to
      spinal metastasis that incorporates SINS. It is easy to remember, it addresses
      clinical factors not directly addressed by other systems, and it is adaptable to
      changes in technology. 

PMID- 25054101
TI  - Correction: Cross-country differences in the association between diabetes and
      disability.

PMID- 25054102
TI  - Prevalence, components and associated demographic and lifestyle factors of the
      metabolic syndrome in type 2 diabetes mellitus.
AB  - BACKGROUND: Adults with the metabolic syndrome (MetS) are twice as likely to die
      from and three times as likely to have a heart attack or stroke compared with
      people without the syndrome. About 70-80% of type 2 diabetes mellitus (type 2 DM)
      patients are diagnosed with the MetS. Investigating the occurrence of the MetS in
      type 2 DM patients is critical for cardiovascular disease prevention. We
      evaluated the prevalence and components of the MetS and its associated clinical
      and demographic factors in a Ghanaian adult population with DM 2. METHODS: This
      cross-sectional study was conducted among 200 previously diagnosed type 2 DM
      patients receiving care from an outpatient clinic of the Tamale Teaching
      Hospital, Ghana. Anthropometric measurements of waist circumference (cm), weight
      (Kg) and height (m) were measured appropriately. Clinical data were obtained from
      the personal health record files of the participants. MetS was defined according
      to the International Diabetes Federation criteria. RESULTS: The prevalence of
      MetS was 24.0% (n=48). The prevalence was higher in women (27.3%, n= 42) compared
      to men (13.0%, n=6). The commonest occurring components of the MetS included
      abdominal obesity (77.0%) and elevated FPG (77.0%) denoting uncontrolled
      diabetes. The prevalence of elevated BP was found to be 44.0%(n=88) and was
      higher in men (56.5%) than in women (40.3%). Factors that were found to be
      associated to the MetS were being overweight/obese (Crude OR = 2.9, 95% CI = 1.43
      - 5.90, p=0.004), ever tried to lose weight (Crude OR = 2.5, 95% CI = 1.24 -
      4.94, p=0.015) and having diabetes for over 5 years (Crude OR = 11.3, 95% CI =
      5.26 - 24.08, p<0.001). Other factors that were associated to the MetS were
      current smokers (Crude OR = 6.8, 95% CI = 1.21- 38.49, p=0.030) and alcohol
      drinkers (Crude OR = 3.1, 95% CI = 1.23 - 7.65, p=0.018). CONCLUSION: A
      comparatively low prevalence of the MetS was found. More females than males had
      the MetS. Uncontrolled diabetes and abdominal obesity were prevalent. The factors
      identified by our univariate logistic regression model were not significant
      predictors of the MetS in our multivariate model.

PMID- 25054103
TI  - Platycosides from the Roots of Platycodon grandiflorum and Their Health Benefits.
AB  - The extracts and pure saponins from the roots of Platycodon grandiflorum (PG) are
      reported to have a wide range of health benefits. Platycosides (saponins) from
      the roots of PG are characterized by a structure containing a triterpenoid
      aglycone and two sugar chains. Saponins are of commercial significance, and their
      applications are increasing with increasing evidence of their health benefits.
      The biological effects of saponins include cytotoxic effects against cancer
      cells, neuroprotective activity, antiviral activity, and cholesterol lowering
      effects. Saponins with commercial value range from crude plant extracts, which
      can be used for their foaming properties, to high purity saponins such as
      platycodin D, which can be used for its health applications (e.g., as a vaccine
      adjuvant). This review reveals that platycosides have many health benefits and
      have the potential to be used as a remedy against many of the major health
      hazards (e.g., cancer, obesity, alzheimer's) faced by populations around the
      world. Methods of platycoside purification and analysis are also covered in this
      review. 

PMID- 25054104
TI  - Ameliorating Effect of Mycoleptodonoides aitchisonii on High-fat Diet-induced
      Obese Mice.
AB  - The present study investigated the anti-obesity effects of Mycoleptodonoides
      aitchisonii (MA) in mice fed a high-fat (HF) diet. Two groups were fed either a
      normal control diet or an HF (45% kcal fat) diet for 12 weeks and three groups
      were fed an HF diet supplemented with powdered MA (MAP, 1%, 3%, and 5%) for 12
      weeks. The anti-obesity effects of MAP supplementation on body weight, fat mass
      development, and lipid-related markers were assessed. Consumption of an HF diet
      resulted in increased body weight, serum lipids, relative adipose tissues weight,
      and liver fat accumulation. However, administration of MAP significantly
      decreased body weight gain, food intake, food efficiency ratio, hepatic
      cholesterol level, and adipose tissue weight in a dose-dependent manner. In
      addition, treatment with MAP significantly reduced the occurrence of fatty liver
      deposits and steatosis, and inhibited an HF diet-induced increase in adipocyte
      size. These results suggest that dietary supplementation with MAP exerts anti
      obesity effects and indicate that MAP could be used as a functional food to
      control obesity. 

PMID- 25054105
TI  - Antioxidant effects of cranberry powder in lipopolysaccharide treated
      hypercholesterolemic rats.
AB  - This study was conducted to investigate the effects of cranberry power on
      antioxidant defense system in rats fed an atherogenic diet and injected with
      lipopolysaccharide (LPS). Sprague-Dawley rats were divided into the following 5
      groups: normal diet+saline (NS), atherogenic diet+saline (AS), atherogenic
      diet+LPS (AL), atherogenic diet with 5% cranberry powder+LPS (AL-C5), and
      atherogenic diet with 10% cranberry powder+LPS (AL-C10). Total antioxidant status
      measured by ferric reducing ability of plasma (FRAP) was significantly reduced by
      LPS injection (24%) and was restored by the cranberry powder treatment (P<0.05).
      In addition, the mean level of plasma total phenolics was significantly decreased
      by LPS injection (P<0.05) and tended to be increased when cranberry powder was
      incorporated in to the diet. Activity of serum superoxide dismutase (SOD) tended
      to be lowered by LPS injection and declined further in cranberry powder fortified
      groups. Overall results indicate that dietary cranberry powder may provide
      appropriate antioxidants to counter the diminished antioxidant status induced by
      exposing hypercholesterolemic rats to LPS. 

PMID- 25054106
TI  - Antioxidant and Anti-inflammatory Effects of Yam (Dioscorea batatas Decne.) on
      Azoxymethane-induced Colonic Aberrant Crypt Foci in F344 Rats.
AB  - Yam (Dioscorea batatas Decne.) has long been used as a health food and oriental
      folk medicine because of its nutritional fortification, tonic, anti-diarrheal,
      anti-inflammatory, antitussive, and expectorant effects. Reactive oxygen species
      (ROS), which are known to be implicated in a range of diseases, may be important
      progenitors of carcinogenesis. The aim of this study was to investigate the
      modulatory effect of yam on antioxidant status and inflammatory conditions during
      azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We measured
      the formation of aberrant crypt foci (ACF), hemolysate antioxidant enzyme
      activities, colonic mucosal antioxidant enzyme gene expression, and colonic
      mucosal inflammatory mediator gene expression. The feeding of yam prior to
      carcinogenesis significantly inhibited AOM-induced colonic ACF formation. In yam
      administered rats, erythrocyte levels of glutathione, glutathione peroxidase
      (GPx), and catalase were increased and colonic mucosal gene expression of Cu/Zn
      superoxide dismutase (SOD), Mn-SOD, and GPx were up-regulated compared to the AOM
      group. Colonic mucosal gene expression of inflammatory mediators (i.e., nuclear
      factor kappaB, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis
      factor alpha, and interleukin-1beta) was suppressed by the yam-supplemented diet.
      These results suggest that yam could be very useful for the prevention of colon
      cancer, as they enhance the antioxidant defense system and modulate inflammatory
      mediators. 

PMID- 25054107
TI  - Antioxidant and Anti-inflammatory Activities of Broccoli Florets in LPS
      stimulated RAW 264.7 Cells.
AB  - Broccoli (Brassica oleracea var. italia) florets were extracted with 80% methanol
      and the extract was sequentially fractionated with n-hexane, ethyl acetate, n
      butanol, and distilled water. The extract and the fractions were evaluated for
      total phenolic content, sulforaphane content, antioxidant activity, and anti
      inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The
      total phenolic content and sulforaphane content of the ethyl acetate fraction
      (EF) were 35.5 mg gallic acid equivalents/g and 620.2 MUg/g, respectively. These
      values were higher than those of the 80% methanol extract and organic solvent
      fractions. The oxygen radical absorbance capacity of the EF [1,588.7 MUM Trolox
      equivalents (TE)/mg] was 11-fold higher than that of the distilled water fraction
      (143.7 MUM TE/mg). The EF inhibited nitric oxide release from LPS-stimulated RAW
      264.7 cells in a dose-dependent manner and inhibited IkappaB-alpha degradation
      and nuclear factor-kappaB activation in LPS-stimulated RAW 264.7 cells. In
      conclusion, the EF of broccoli florets exerted potent antioxidant and anti
      inflammatory effects. 

PMID- 25054108
TI  - Characteristics and in vitro Anti-diabetic Properties of the Korean Rice Wine,
      Makgeolli Fermented with Laminaria japonica.
AB  - New in vitro anti-diabetes makgeolli was produced from rice by adding various
      quantities of Laminaria japonica, and the fermentation characteristics of the L.
      japonica makgeolli during the fermentation process were investigated. The
      contents of alcohol and reducing sugar, and viable count of yeast, of L. japonica
      makgeolli were not significantly changed when the proportion of L. japonica was
      increased. The total acid content decreased with an increase in L. japonica
      concentration; the pH and total bacterial cell count increased in proportion with
      the increase in L. japonica concentration. The L. japonica makgeolli contents of
      free sugars, such as fructose, glucose, and sucrose, and of organic acids, such
      as acetic acid, citric acid, succinic acid, and lactic acid, were altered during
      fermentation and showed various patterns. The effects of the quantity of L.
      japonica added on the acceptability and anti-diabetes activities of L. japonica
      makgeolli were also investigated. In a sensory evaluation, L. japonica makgeolli
      brewed by adding 2.5 or 5% L. japonica to the mash showed the best overall
      acceptability; the 12.5% L. japonica sample was least favored due to its seaweed
      flavor. L. japonica addition did not increase the peroxynitrite-scavenging
      activity of makgeolli. L. japonica makgeolli showed potent anti-diabetes
      activity, particularly that containing >7.5% L. japonica. Therefore, L. japonica
      makgeolli may represent a new functional makgeolli with anti-diabetes properties.

PMID- 25054109
TI  - Comparison of the effects of blending and juicing on the phytochemicals contents
      and antioxidant capacity of typical korean kernel fruit juices.
AB  - Four Korean kernel fruit (apple, pear, persimmon, and mandarin orange) juices
      were obtained by household processing techniques (i.e., blending, juicing). Whole
      and flesh fractions of each fruit were extracted by a blender or a juicer and
      then examined for phytochemical content (i.e., organic acids, polyphenol
      compounds). The antioxidant capacity of each juice was determined by ferric
      reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      assays. Results revealed that juices that had been prepared by blending whole
      fruits had stronger antioxidant activities and contained larger amounts of
      phenolic compounds than juices that had been prepared by juicing the flesh
      fraction of the fruit. However, the concentration of ascorbic acid in apple,
      pear, and mandarin orange juices was significantly (P<0.05) higher in juice that
      had been processed by juicing, rather than blending. The juices with the highest
      ascorbic acid (233.9 mg/serving), total polyphenols (862.3 mg gallic acid
      equivalents/serving), and flavonoids (295.1 mg quercetin equivalents/serving)
      concentrations were blended persimmon juice, blended mandarin orange juice, and
      juiced apple juice, respectively. These results indicate that juice extraction
      techniques significantly (P<0.05) influences the phytochemical levels and
      antioxidant capacity of fruit juices. 

PMID- 25054110
TI  - Effect of partial replacement of wheat flour with high quality cassava flour on
      the chemical composition, antioxidant activity, sensory quality, and microbial
      quality of bread.
AB  - IN THE CURRENT STUDY, WHEAT FLOUR WAS MIXED WITH HIGH QUALITY CASSAVA FLOUR
      (HQCF) IN SEVERAL RATIOS: 90:10, 80:20, 70:30, and 60:40, and used to prepare
      10%, 20%, 30%, and 40% National Root Crops Research Institute (NRCRI) cassava
      bread, respectively. 100% wheat bread was prepared as a control (100% wheat
      bread). Five bread samples were prepared per group. Antioxidant assays [i.e., 2,2
      diphenyl- 1-picrylhydrazyl radical (DPPH) scavenging assay, reducing power assay]
      revealed that the bread samples had considerable antioxidant capacities.
      Substitution of wheat flour with HQCF at various concentrations resulted in dose
      dependent decreases in the mineral and protein contents of the resulting bread
      samples. The crude fiber content of the bread samples was minimal, while the
      carbohydrate content of the bread samples ranged from 43.86% to 48.64%. A 20%
      substitution of wheat flour with HQCF yielded bread samples with a general
      acceptability that was comparable to that of 100% wheat bread. The mean bacteria
      counts of the bread samples ranged from 2.0*10(3) CFU/mL to 1.4*10(4) CFU/mL,
      while the fungal counts ranged from 0 CFU/mL to 3*10(3) CFU/mL. There was a
      positive correlation between the DPPH antioxidant activities and the reducing
      powers of the bread samples (R(2)=0.871) and a positive correlation between the
      DPPH antioxidant activities and the flavonoid contents of the bread samples
      (R(2)=0.487). The higher microbial load of the NRCRI cassava bread samples
      indicates that these bread samples may have a shorter shelf life than the 100%
      wheat bread. The significant positive correlation between total flavonoid content
      and reducing power (R(2)=0.750) suggests that the flavonoids present in the
      lipophilic fractions of the bread samples could be responsible for the reductive
      capacities of the bread samples. 

PMID- 25054111
TI  - The Effect of Extrusion Conditions on Water-extractable Arabinoxylans from Corn
      Fiber.
AB  - The effect of feed moisture contents (30%, 40%, and 50%) and screw speed (200
      rpm, 250 rpm, and 300 rpm) on the corn fiber gum (CFG) yield and soluble
      arabinoxylans (SAX) content of destarched corn fiber was investigated. The CFG
      yields and SAX contents of extruded, destarched corn fiber were higher than that
      of destarched corn fiber. In extruded, destarched corn fiber, increased screw
      speed and decreased feed moisture contents resulted in a higher SAX contents. The
      maximum yields of CFG obtained from extruded, destarched corn fiber were 79.1+/
      19.0 g/kg (30% feed moisture content) and 82.3+/-11.30 g/kg (300 rpm screw
      speed). The highest SAX content was also observed at a screw speed of 300 rpm.
      The results of the present study show that water extraction and extrusion
      combined have the potential to increase CFG and SAX yields from corn fiber. 

PMID- 25054112
TI  - Lack of reversibility for NOACs.

PMID- 25054113
TI  - Response to 'Lack of reversibility for NOACs'.

PMID- 25054114
TI  - The expanding role of lipoprotein apheresis in the treatment of raised
      lipoprotein(a) in ischaemic heart disease and refractory angina.
AB  - It is increasingly recognised that lipoprotein(a) [Lp(a)], an inherited,
      genetically-determined form of LDL-cholesterol, is an independent cardiovascular
      risk factor and predictor of adverse cardiovascular outcomes. Lp(a) is felt to
      increase cardiovascular risk via its pro-thrombotic effect and by enhancing
      intimal lipoprotein deposition. Lipoprotein apheresis is currently the most
      effective treatment for raised Lp(a). There is a growing body of evidence
      suggesting that aggressively lowering raised Lp(a) may improve cardiovascular and
      clinical outcomes, although much more research is required in this field. Angina
      which is refractory to conventional medical therapy and revascularisation, is
      extremely challenging to manage. Treatment options for such patients remain very
      limited. We describe the case of a patient with refractory angina and raised
      lipoprotein(a) in whom aggressive reduction of Lp(a) with lipoprotein apheresis
      successfully ameliorated the progression of coronary stenosis and provided
      effective and durable relief of angina symptoms. In our centre, we are currently
      conducting a prospective, randomised controlled cross-over study of patients with
      refractory angina and raised Lp(a), randomised to undergoing lipoprotein
      apheresis or 'sham' apheresis with assessment of myocardial perfusion, carotid
      atherosclerosis, endothelial vascular function, thrombogenesis, oxidised
      phospholipids and their antibodies, exercise capacity, angina symptoms and
      quality of life at the beginning and end of treatment. 

PMID- 25054115
TI  - Coronary heart disease in Indian Asians.
AB  - The Indian Asian population accounts for a fifth of all global deaths from
      coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled
      since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying
      the increased CHD mortality among Indian Asians remain unknown. Although
      conventional cardiovascular risk factors contribute to CHD in Indian Asians as in
      other populations, these do not account for their increased risk. Type-2
      diabetes, insulin resistance and related metabolic disturbances are more
      prevalent amongst Indian Asians than Europeans, and have been proposed as major
      determinants of higher CHD risk among Indian Asians. However, this view is not
      supported by prospective data. Genome-wide association studies have not
      identified differences in allele frequencies or effect sizes in known loci to
      explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms
      underlying higher CHD risk amongst Indian Asians presents a major obstacle to
      reducing the burden of CHD in this population. Systems biology approaches such as
      genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased
      approach for discovery of novel biomarkers and disease pathways underlying CHD.
      Incorporation of these 'omic' approaches in prospective Indian Asian cohorts such
      as the London Life Sciences Population Study (LOLIPOP) provide an exciting
      opportunity for the identification of new risk factors underlying CHD in this
      high risk population. 

PMID- 25054117
TI  - TASTE: To aspirate, or not to aspirate, remains a question.

PMID- 25054118
TI  - HEAT-PPCI: A clear and welcome win for heparin.
AB  - The use of bivalirudin during primary percutaneous coronary intervention (PPCI)
      is perceived to be associated with less bleeding compared to unfractionated
      heparin (UFH). However, evidence supporting this observation is confounded by the
      frequent co-administration of glycoprotein IIb/IIIa inhibitors in the UFH arm in
      the majority of previous large trials. The "How Effective Are Antithrombotic
      Therapies in Primary PCI (HEAT-PPCI)" trial was conducted to test the efficacy
      and safety of UFH vesrus bivalirudin in patients undergoing PPCI when GP IIb/IIIa
      inhibitors are used selectively. 

PMID- 25054119
TI  - STAMPEDE: Bariatric surgery gains more evidence based support.
AB  - Diabetes mellitus (DM) and obesity are associated with significant morbidity and
      mortality. Recent large-scale trials of intensive medical management for obesity
      and diabetes have been disappointing. Observational studies and small-scale
      trials of bariatric surgery on DM patients have shown promising results. The
      effects of sleeve gastrectomy and gastric bypass in a larger cohort of patients
      with DM and obesity was tested in the STAMPEDE trial over a 3-year follow-up. 

PMID- 25054116
TI  - Improved understanding of the pathophysiology of atrial fibrillation through the
      lens of discrete pathological pathways.
AB  - Atrial fibrillation (AF) is a common disorder with a complex and incompletely
      understood pathophysiology. Genetic approaches to understanding the
      pathophysiology of AF have led to the identification of several biological
      pathways important in the pathogenesis of the arrhythmia. These include pathways
      important for cardiac development, generation and propagation of atrial
      electrical impulses, and atrial remodeling and fibrosis. While common and rare
      genetic variants in these pathways are associated with increased susceptibility
      to AF, they differ substantially among patients with lone versus typical AF.
      Furthermore, how these pathways converge to a final common clinical phenotype of
      AF is unclear and might also vary among different patient populations. Here, we
      review the contemporary knowledge of AF pathogenesis and discuss how derangement
      in cardiac development, ion channel dysfunction, and promotion of atrial fibrosis
      may contribute to this common and important clinical disorder. 

PMID- 25054121
TI  - Editors' page.

PMID- 25054120
TI  - The wide spectrum of aortic root dilatation after the Ross operation.

PMID- 25054123
TI  - TAVI: New trials and registries offer further welcome evidence - U.S. CoreValve,
      CHOICE, and GARY.
AB  - The introduction of transcatheter aortic valve implantation (TAVI) has resulted
      in a paradigm shift in the treatment of patients with severe aortic stenosis.
      Data from the recent U.S CoreValve Trial suggest, for the first time, that TAVI
      is associated with a significantly higher rate of survival at one year compared
      to surgical aortic valve replacement (SAVR) in the treatment of high-risk
      patients affected by severe aortic stenosis. The present review discusses this
      study and the current evidence about TAVI, for the treatment of severe aortic
      stenosis, from major trials and real world registries. 

PMID- 25054124
TI  - RE-ALIGN: First trial of novel oral anticoagulant in patients with mechanical
      heart valves - The search continues.

PMID- 25054125
TI  - Aneurysm of the right sinus of Valsalva and the membranous septum: Haemodynamic
      and clinical characterization.

PMID- 25054126
TI  - SYMPLICITY HTN 3: The death knell for renal denervation in hypertension?
AB  - Resistant hypertension is, by definition, a challenge to most physicians treating
      hypertension. Renal sympathetic denervation has shown promising early results in
      treating this condition. The SYMPLICITY HTN-3 is the most recent trial to report
      the effects of this technique on resistant hypertension. This review discusses
      this study and its surprising neutral results before ending with an overview of
      key lessons learned. 

PMID- 25054122
TI  - The living aortic valve: From molecules to function.
AB  - The aortic valve lies in a unique hemodynamic environment, one characterized by a
      range of stresses (shear stress, bending forces, loading forces and strain) that
      vary in intensity and direction throughout the cardiac cycle. Yet, despite its
      changing environment, the aortic valve opens and closes over 100,000 times a day
      and, in the majority of human beings, will function normally over a lifespan of
      70-90 years. Until relatively recently heart valves were considered passive
      structures that play no active role in the functioning of a valve, or in the
      maintenance of its integrity and durability. However, through clinical experience
      and basic research the aortic valve can now be characterized as a living, dynamic
      organ with the capacity to adapt to its complex mechanical and biomechanical
      environment through active and passive communication between its constituent
      parts. The clinical relevance of a living valve substitute in patients requiring
      aortic valve replacement has been confirmed. This highlights the importance of
      using tissue engineering to develop heart valve substitutes containing living
      cells which have the ability to assume the complex functioning of the native
      valve. 

PMID- 25054127
TI  - Coronary artery systolic "milking" and "bridging" in Takotsubo syndrome:
      substrate or an epiphenomenon?

PMID- 25054128
TI  - Response to: Coronary artery systolic "milking" and "bridging" in Takotsubo
      syndrome: substrate or an epiphenomenon?

PMID- 25054129
TI  - Challenges for nerve repair using chitosan-siloxane hybrid porous scaffolds.
AB  - The treatment of peripheral nerve injuries remains one of the greatest challenges
      of neurosurgery, as functional recover is rarely satisfactory in these patients.
      Recently, biodegradable nerve guides have shown great potential for enhancing
      nerve regeneration. A major advantage of these nerve guides is that no foreign
      material remains after the device has fulfilled its task, which spares a second
      surgical intervention. Recently, we studied peripheral nerve regeneration using
      chitosan-gamma-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid
      membranes. In our studies, these porous membranes significantly improved nerve
      fiber regeneration and functional recovery in rat models of axonotmetic and
      neurotmetic sciatic nerve injuries. In particular, the number of regenerated
      myelinated nerve fibers and myelin thickness were significantly higher in rat
      treated with chitosan porous hybrid membranes, whether or not they were used in
      combination with mesenchymal stem cells isolated from the Wharton's jelly of the
      umbilical cord. In this review, we describe our findings on the use of chitosan
      GPTMS hybrids for nerve regeneration. 

PMID- 25054130
TI  - Molecular mechanisms of curcumin on diabetes-induced endothelial dysfunctions:
      Txnip, ICAM-1, and NOX2 expressions.
AB  - We aim to investigate the effects of curcumin on preventing diabetes-induced
      vascular inflammation in association with its actions on Txnip, ICAM-1, and NOX2
      enzyme expressions. Male Wistar rats were divided into four groups: control
      (CON), diabetic (DM; streptozotocin (STZ), i.v. 55 mg/kg BW), control-treated
      with curcumin (CONCUR; 300 mg/kg BW), and diabetes treated with curcumin (DMCUR;
      300 mg/kg BW). 12th week after STZ injection, iris blood perfusion, leukocyte
      adhesion, Txnip, p47phox, and malondialdehyde (MDA) levels were determined by
      using laser Doppler, intravital fluorescent confocal microscopy, Western Blot
      analysis, and TBAR assay, respectively. The iris blood perfusion of DM and DMCUR
      was decreased significantly compared to CON and CONCUR (P < 0.001). Plasma
      glucose and HbA1c of DM and DMCUR were increased significantly compared to CON
      and CONCUR (P < 0.001). Leukocyte adhesion, ICAM-1, p47phox expression, and MDA
      levels in DM were increased significantly compared to CON, CONCUR, and DMCUR (P <
      0.05). Txnip expression in DM and DMCUR was significantly higher than CON and
      CONCUR (P < 0.05). From Pearson's analysis, the correlation between the plasma
      MDA level and the endothelial functions was significant. It suggested that
      curcumin could ameliorate diabetic vascular inflammation by decreasing ROS
      overproduction, reducing leukocyte-endothelium interaction, and inhibiting ICAM-1
      and NOX2 expression.

PMID- 25054131
TI  - Rank-based miRNA signatures for early cancer detection.
AB  - We describe a new signature definition and analysis method to be used as
      biomarker for early cancer detection. Our new approach is based on the
      construction of a reference map of transcriptional signatures of both healthy and
      cancer affected individuals using circulating miRNA from a large number of
      subjects. Once such a map is available, the diagnosis for a new patient can be
      performed by observing the relative position on the map of his/her
      transcriptional signature. To demonstrate its efficacy for this specific
      application we report the results of the application of our method to published
      datasets of circulating miRNA, and we quantify its performance compared to
      current state-of-the-art methods. A number of additional features make this
      method an ideal candidate for large-scale use, for example, as a mass screening
      tool for early cancer detection or for at-home diagnostics. Specifically, our
      method is minimally invasive (because it works well with circulating miRNA), it
      is robust with respect to lab-to-lab protocol variability and batch effects (it
      requires that only the relative ranking of expression value of miRNA in a profile
      be accurate not their absolute values), and it is scalable to a large number of
      subjects. Finally we discuss the need for HPC capability in a widespread
      application of our or similar methods. 

PMID- 25054132
TI  - Low density lipoprotein-containing circulating immune complexes: role in
      atherosclerosis and diagnostic value.
AB  - It has been suggested that low density lipoprotein-containing circulating immune
      complexes (LDL-CIC) play a role in atherogenesis and are involved in the
      formation of early atherosclerotic lesion. These complexes, as well as anti-LDL
      autoantibodies, have been found in the blood and in the atherosclerotic lesions
      of patients with different cardiovascular diseases, as well as in the blood of
      animals with experimental atherosclerosis. It can be suggested that the presence
      of anti-LDL antibodies in the blood is a result of immune response induced by
      lipoprotein modification. LDL-CIC differs from native LDL in many aspects. It has
      much lower sialic acid content, smaller diameter, and higher density and is more
      electronegative than native LDL. Fraction of LDL-CICs is fundamental to the serum
      atherogenicity manifested at the cellular level. LDL-CIC, unlike native LDL, is
      able to induce intracellular accumulation of neutral lipids, especially
      esterified cholesterol, in cells cultured from uninvolved human aortic intima and
      in macrophage cultures. After removal of LDL-CIC, the CHD patient's sera lose
      their atherogenic properties. Titer of LDL-CIC in blood serum significantly
      correlates with progression of atherosclerosis in human in vivo and has the
      highest diagnostic value among other measured serum lipid parameters. Elevated
      CIC-cholesterol might well be a possible risk factor of coronary atherosclerosis.

PMID- 25054133
TI  - Poststroke neuropsychiatric symptoms: relationships with IL-17 and oxidative
      stress.
AB  - Stroke variably activates interleukin- (IL-) 17 expression, reduces regulatory T
      cells, and induces oxidative stress, which may support neurodegeneration.
      Ischemic stroke patients were screened for depressive symptoms (Center for
      Epidemiological Studies Depression (CES-D)) and cognitive status (Mini Mental
      State Examination). Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN
      ] gamma), anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH), a
      measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age
      71.8 +/- 14.4 years, 36% female), 19 had depressive symptoms (CES-D >= 16), which
      was associated with poorer cognitive status (F 1,46 = 8.44, P = 0.006). IL-17
      concentrations did not differ between subjects with and without depressive
      symptoms (F 1,46 = 8.44, P = 0.572); however, IL-17 was associated with poorer
      cognitive status in subjects with depressive symptoms (F 1,46 = 9.29, P = 0.004).
      In those subjects with depressive symptoms, IL-17 was associated with higher LPH
      (rho = 0.518, P = 0.023) and lower IL-10 (rho = -0.484, P = 0.036), but not in
      those without. In conclusion, poststroke depressive symptoms may be associated
      with cognitive vulnerability to IL-17 related pathways, involving an imbalance
      between proinflammatory and anti-inflammatory activity and increased oxidative
      stress. 

PMID- 25054134
TI  - Synthesis and evaluation of novel pyrroles and pyrrolopyrimidines as anti
      hyperglycemic agents.
AB  - A series of pyrrole and pyrrolopyrimidine derivatives were examined for their in
      vivo antihyperglycemic activity. Compounds Ia-c,e, and IVg showed promising
      antihyperglycemic activity equivalent to a well-known standard antihyperglycemic
      drug, Glimepiride (Amaryl, 4 mg/kg). In this paper, we examine and discuss the
      structure-activity relationships and antihyperglycemic activity of these
      compounds.

PMID- 25054135
TI  - Preliminary evaluation of probiotic properties of Lactobacillus strains isolated
      from Sardinian dairy products.
AB  - Twenty-three Lactobacillus strains of dairy origin were evaluated for some
      functional properties relevant to their use as probiotics. A preliminary
      subtractive screening based on the abilities to inhibit the growth of microbial
      pathogens and hydrolyze conjugated bile salts was applied, and six strains were
      selected for further characterization including survival under gastrointestinal
      environmental conditions, adhesion to gut epithelial tissue, enzymatic activity,
      and some safety properties. All selected strains maintained elevated cell numbers
      under conditions simulating passage through the human gastrointestinal tract,
      well comparable to the values obtained for the probiotic strain Lactobacillus
      rhamnosus GG, and were able to adhere to Caco-2 cells to various extents (from 3
      to 20%). All strains exhibited high aminopeptidase, and absent or very low
      proteolytic and strong beta-galactosidase activities; none was found to be
      haemolytic or to produce biogenic amines and all were susceptible to
      tetracycline, chloramphenicol, erythromycin, ampicillin, and
      amoxicillin/clavulanic acid. Our results indicate that the Lactobacillus strains
      analyzed could be considered appropriate probiotic candidates, due to resistance
      to GIT simulated conditions, antimicrobial activity, adhesion to Caco-2 cell
      line, and absence of undesirable properties. They could be used as adjunct
      cultures for contributing to the quality and health related functional properties
      of dairy products. 

PMID- 25054136
TI  - Allele frequency of ABO blood group antigen and the risk of esophageal cancer.
AB  - BACKGROUND: ABO blood group and risk of squamous cell carcinoma of esophagus have
      been reported by many studies, but there is no discipline that had provided
      association with the genotype and gene frequency by population statics. METHODS:
      We conducted a case-control study on 480 patients with squamous cell carcinoma of
      the esophagus and 480 noncancer patients. ABO blood group was determined by
      presence of antigen with the help of monoclonal antibody. Chi-square test and
      odds ratio (OR) with 95% confidence intervals (CIs) were calculated by
      statistical methods, and gene frequencies were calculated by Hardy-Weinberg
      model. RESULTS: We observed significant associations between ABO genotype and
      squamous cell carcinoma of esophagus. OR (95% CIs) was 1.69 (1.31-2.19) for
      presence of B antigen allele relative to its absence (P < 0.0001); in female
      subgroup OR (95% CIs) observed at 1.84 (1.27-2.65) was statistically significant
      (P = 0.001). SCC of esophagus shows significant difference in comparison to
      general population; blood group B is found to be higher in incidence (P =
      0.0001). Increased risk of cancer was observed with absence of Rh antigen (P =
      0.0001). Relatively increased gene frequency of q[B] allele is observed more
      significantly in female cancer patients (P = 0.003). CONCLUSION: Statistically
      significant association between squamous cell carcinoma of the esophagus and ABO
      and Rh genotype is identified by this study. Sex and anatomical site of cancer
      also present with statistically significant relative association. However, larger
      randomised trials are required to establish the hypothesis.

PMID- 25054137
TI  - Regional anesthesia for postoperative pain control.

PMID- 25054139
TI  - In vitro antimicrobial and antiprotozoal activities, phytochemical screening and
      heavy metals toxicity of different parts of Ballota nigra.
AB  - The study was done to assess the phytochemicals (flavonoids, terpenoids,
      saponins, tannin, alkaloids, and phenol) in different parts (root, stem, and
      leaves) of Ballota nigra and correlated it to inhibition of microbes (bacteria
      and fungi), protozoan (Leishmania), and heavy metals toxicity evaluation. In root
      and stem flavonoids, terpenes and phenols were present in ethanol, chloroform,
      and ethyl acetate soluble fraction; these were found to be the most active
      inhibiting fractions against all the tested strains of bacteria, fungi, and
      leishmania. While in leaves flavonoids, terpenes, and phenols were present in
      ethanol, chloroform, and n-butanol fractions which were the most active fractions
      against both types of microbes and protozoan (leishmania) in in vitro study.
      Ethanol and chloroform fractions show maximum inhibition against Escherichia coli
      (17 mm). The phytochemical and biological screenings were correlated with the
      presence of heavy metals in selected plant Ballota nigra. Cr was found above
      permissible value (above 1.5 mg/kg) in all parts of the plant. Ni was above WHO
      limit in B. nigra root and leaves (3.35 +/- 1.20 mg/kg and 5.09 +/- 0.47 mg/kg,
      respectively). Fe was above permissible value in all parts of B. nigra (above 20
      mg/kg). Cd was above permissible value in all parts of the plant (above 0.3
      mg/kg). Pb was above WHO limit (above 2 mg/kg) in all parts of Ballota nigra.

PMID- 25054138
TI  - Investigation of estrogen receptor (ESR1) for breast cancer from traditional
      Chinese medicine.
AB  - Recently, an important topic of breast cancer had been published in 2013. In this
      report, estrogen receptor (ESR1) had defined the relation of hormone-cause breast
      cancer. The screening of traditional Chinese medicine (TCM) database has found
      the molecular compounds by simulating molecular docking and molecular dynamics to
      regulate ESR1. S-Allylmercaptocysteine and 5-hydroxy-L-tryptophan are selected
      according to the highest docking score than that of other TCM compounds and
      Raloxifene (control). The simulation from molecular dynamics is helpful in
      analyzing and detecting the protein-ligand interactions. After a comparing the
      control and the Apo form, then based on the docking poses, hydrophobic
      interactions, hydrogen bond and structure variations, this research postulates
      that S-allylmercaptocysteine may be more appropriate than other compounds for
      protein-ligand interaction. 

PMID- 25054140
TI  - Differential response of oyster shell powder on enzyme profile and nutritional
      value of oyster mushroom Pleurotus florida PF05.
AB  - Oyster mushroom Pleurotus florida was cultivated on different combinations of
      wheat straw (WS) as basal substrate and oyster shell powder (OSP) supplement. The
      OSP supplementation considerably responded to different cultivation phases. The
      mycelium grew fast and showed rapid growth rate (8.91 mmd(-1)) in WS + OSP (97 +
      3) combination while WS + OSP (92 + 8) showed maximum laccase (3.133 U/g) and Mn
      peroxidase (MnP) activities (0.091 U/g). The climax level of laccase (5.433 U/g)
      and MnP (0.097 U/g) was recorded during fruit body initiation in WS + OSP (97 +
      3) and WS + OSP (98 + 2) combinations, respectively. The WS + OSP (97 + 3)
      combination represented the best condition for mushroom cultivation and produced
      the highest biological efficiency (147%). In addition, protein and lipid contents
      in fruit bodies were slightly improved in response to OSP. The carbohydrate was
      significantly increased by raising concentration of OSP. The highest values of
      protein, carbohydrate, and lipid noted were 31.3 MUg/g, 0.0639 (g/g), and 0.373
      (g/g) correspondingly. Conclusively it was evident that lower concentrations of
      OSP acted positively and relatively to higher concentrations and improved
      nutritional content which may suitably be used to enhance both yield and
      nutritional values of mushroom.

PMID- 25054141
TI  - Helicobacter pylori is not eradicated after triple therapy: a nested PCR based
      study.
AB  - Detection of Helicobacter pylori after triple therapy is usually carried out by
      either rapid urease test (RUT), urea breath test (UBT), histology, bacterial
      isolation, and single round PCR or serological tests. In this study, antral
      biopsy specimens from 25 patients were tested for H. pylori by RUT, culture,
      histology, and nested PCR in their antral biopsy specimens before and after
      treatment. Three genes, namely, heat shock protein (hsp60), phosphoglucosamine
      mutase (ureC), and flagellar export ATP synthase (fliI) of H. pylori were
      targeted. Of the 25 antral biopsy specimens, the RUT, culture, histology, and
      nested PCR positivity dropped from 81.8% to 12%, 31% to 0%, 100 to 84%, and 100%
      to 92%, respectively, before and after therapy. Further, hsp60 specific amplicons
      from 23 out of 25 patients gave identical restriction pattern, while 6 fliI and 1
      ureC specific amplicon produced different restriction pattern. Furthermore,
      variations in fliI gene sequences in H. pylori after treatment were also
      confirmed by sequencing and compared in silico. Nested PCR based detection of H.
      pylori is more sensitive method to detect H. pylori after therapy than culture,
      RUT, and histology. Further, this study suggests that H. pylori is not eradicated
      completely after triple therapy. 

PMID- 25054142
TI  - A novel missense mutation in oncostatin M receptor beta causing primary localized
      cutaneous amyloidosis.
AB  - Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused
      by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has
      been mapped earlier to pathogenic missense mutations in the OSMR gene, which
      encodes the oncostatin M receptor beta subunit (OSMRbeta). OSMRbeta is
      interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M
      and interleukin-31, which both have biologic roles in inflammation and
      keratinocyte cell proliferation, differentiation, and apoptosis. Here, we
      identified a new OSMR mutation in a Kurdish family for the first time. Blood
      samples were taken from all the affected individuals in the family. DNA
      extraction was performed using salting out technique. Primers were designed for
      intron flanking individual exons of OSMR gene which were subjected to direct
      sequencing after PCR amplification for each sample. Sequencing showed a C/T
      substitution at position 613 in the proband. This mutation results in an L613S
      (leucine 613 to serine) amino acid change. The identified mutation was observed
      in all affected family members but not in 100 ethnically matched healthy
      controls. Elucidating the molecular basis of familial PLCA provides new insight
      into mechanisms of itch in human skin and may lead to new therapeutic targets for
      pruritus. 

PMID- 25054143
TI  - Increased oxidative damage associated with unfavorable cytogenetic subgroups in
      chronic lymphocytic leukemia.
AB  - Oxidative stress contributes to genomic instability in chronic lymphocytic
      leukemia (CLL), but its relationship with the acquisition of specific chromosomal
      abnormalities is unknown. We recruited 55 untreated CLL patients and assessed 8
      oxo-2'-deoxyguanosine (8-oxo-dG), glutathione, and malondialdehyde (MDA) levels,
      and we compared them among the cytogenetic subgroups established using
      fluorescence in situ hybridization (FISH). Significant increases in 8-oxo-dG
      and/or MDA were observed in patients with unfavorable cytogenetic aberrations
      (17p and 11q deletions) compared to the 13q deletion group. TP53 deletion
      patients exhibited a diminished DNA repair efficiency. Finally, cases with normal
      FISH also showed enhanced 8-oxo-dG, which could result in adverse outcomes. 

PMID- 25054144
TI  - Evaluation of corneal deformation analyzed with Scheimpflug based device in
      healthy eyes and diseased ones.
AB  - This study was designed to evaluate the correlation between corneal biomechanical
      and morphological data in healthy eyes, eyes that underwent myopic
      photorefractive keratectomy (PRK), keratoconus affected eyes, and keratoconus
      affected eyes that underwent corneal collagen crosslinking (CCC). Complete
      clinical eye examination of all eyes was followed by tomographic (Pentacam,
      Oculus, Wetzlar, Germany) and biomechanical (Corvis ST, Oculus, Wetzlar, Germany)
      evaluation. Differences among Corvis ST (CST) parameters in the different groups
      have been performed. Linear regression between central corneal thickness (CCT),
      intraocular pressure (IOP), and anterior corneal curvature measured with Sim'K
      (KM), versus corneal deformation parameters measured with Corvis ST in the
      different groups, has been run using SPSS software version 18.0. We evaluated 64
      healthy eyes of 64 patients with a mean refractive error of -0.65 +/- 1.68 D
      (measured as spherical equivalent), 17 eyes of 17 patients that underwent myopic
      PRK for a mean refractive defect of -4.91 +/- 2.05 D (measured as spherical
      equivalent), 16 eyes of 16 patients affected by keratconus (stage 2-3 of Amsler
      Classification), and 13 eyes of 13 patients affected by keratoconus that
      underwent CCC. Our data suggest that corneal curvature would have a greater
      influence on corneal deformation than CCT; in fact KM values are more strongly
      associated with more CST parameters both about corneal change in shape and both
      about the corneal ability to come back at original shape.

PMID- 25054145
TI  - Bone marrow-derived mesenchymal cell differentiation toward myogenic lineages:
      facts and perspectives.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs) are valuable platforms for
      new therapies based on regenerative medicine. BM-MSCs era is coming of age since
      the potential of these cells is increasingly demonstrated. In fact, these cells
      give origin to osteoblasts, chondroblasts, and adipocyte precursors in vitro, and
      they can also differentiate versus other mesodermal cell types like skeletal
      muscle precursors and cardiomyocytes. In our short review, we focus on the more
      recent manipulations of BM-MSCs toward skeletal and heart muscle differentiation,
      a growing field of obvious relevance considering the toll of muscle disease
      (i.e., muscular dystrophies), the heavier toll of heart disease in developed
      countries, and the still not completely understood mechanisms of muscle
      differentiation and repair. 

PMID- 25054146
TI  - Homozygous inactivating mutation in NANOS3 in two sisters with primary ovarian
      insufficiency.
AB  - Despite the increasing understanding of female reproduction, the molecular
      diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA
      binding protein NANOS3 poses as an interesting candidate gene for POI since
      members of the Nanos family have an evolutionarily conserved function in germ
      cell development and maintenance by repressing apoptosis. We performed mutational
      analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated
      POI, presenting with primary or secondary amenorrhea, and in ethnically-matched
      control women. A homozygous p.Glu120Lys mutation in NANOS3 was identified in two
      sisters with primary amenorrhea. The substituted amino acid is located within the
      second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico
      molecular modelling suggests destabilization of protein-RNA interaction. In vitro
      analyses of apoptosis through flow cytometry and confocal microscopy show that
      NANOS3 capacity to prevent apoptosis was impaired by this mutation. The
      identification of an inactivating missense mutation in NANOS3 suggests a
      mechanism for POI involving increased primordial germ cells (PGCs) apoptosis
      during embryonic cell migration and highlights the importance of NANOS proteins
      in human ovarian biology. 

PMID- 25054147
TI  - Affective dependence and aggression: an exploratory study.
AB  - INTRODUCTION: Emotionally dependent subjects may engage in controlling,
      restrictive, and aggressive behaviours, which limit their partner's autonomy. The
      underlying causes of such behaviours are not solely based on levels of
      aggression, but act as a mean of maintaining the subject's own sense of self
      worth, identity, and general functioning. OBJECTIVE: The aim of the paper is to
      explore the correlation between affective dependency and reactive/proactive
      aggression and to evaluate individual differences as predisposing factors for
      aggressive behaviour and emotional dependency. METHODS: The Spouse-Specific
      Dependency Scale (SSDS) and the Reactive Proactive Questionnaire (RPQ) were
      administered to a sample of 3375 subjects. RESULTS: In the whole sample, a
      positive correlation between emotional dependency and proactive aggression was
      identified. Differences with regard to sex, age group, and geographical
      distribution were evidenced for the scores of the different scales. CONCLUSION: A
      fundamental distinction between reactive and proactive aggression was observed,
      anchoring proactive aggression more strictly to emotional dependency.
      Sociocultural and demographical variables, together with the previous structuring
      of attachment styles, help to determine the scope, frequency, and intensity of
      the demands made to the partner, as well as to feed the fears of loss,
      abandonment, or betrayal.

PMID- 25054148
TI  - Hypoxia in diabetic kidneys.
AB  - Diabetic nephropathy (DN) is now a leading cause of end-stage renal disease. In
      addition, DN accounts for the increased mortality in type 1 and type 2 diabetes,
      and then patients without DN achieve long-term survival compatible with general
      population. Hypoxia represents an early event in the development and progression
      of DN, and hypoxia-inducible factor- (HIF-) 1 mediates the metabolic responses to
      renal hypoxia. Diabetes induces the "fraternal twins" of hypoxia, that is,
      pseudohypoxia and hypoxia. The kidneys are susceptible to hyperoxia because they
      accept 20% of the cardiac output. Therefore, the kidneys have specific
      vasculature to avoid hyperoxia, that is, AV oxygen shunting. The NAD-dependent
      histone deacetylases (HDACs) sirtuins are seven mammalian proteins, SIRTs 1-7,
      which are known to modulate longevity and metabolism. Recent studies demonstrated
      that some isoforms of sirtuins inhibit the activation of HIF by deacetylation or
      noncatalyzing effects. The kidneys, which have a vascular system that protects
      them against hyperoxia, unfortunately experience extraordinary hypernutrition
      today. Then, an unexpected overload of glucose augments the oxygen consumption,
      which ironically results in hypoxia. This review highlights the primary role of
      HIF in diabetic kidneys for the metabolic adaptation to diabetes-induced hypoxia.

PMID- 25054149
TI  - Biological assessment of a calcium silicate incorporated hydroxyapatite-gelatin
      nanocomposite: a comparison to decellularized bone matrix.
AB  - Our laboratory utilized biomimicry to develop a synthetic bone scaffold based on
      hydroxyapatite-gelatin-calcium silicate (HGCS). Here, we evaluated the potential
      of HGCS scaffold in bone formation in vivo using the rat calvarial critical-sized
      defect (CSD). Twelve Sprague-Dawley rats were randomized to four groups: control
      (defect only), decellularized bone matrix (DECBM), and HGCS with and without
      multipotent adult progenitor cells (MAPCs). DECBM was prepared by removing all
      the cells using SDS and NH4OH. After 12 weeks, the CSD specimens were harvested
      to evaluate radiographical, histological, and histomorphometrical outcomes. The
      in vitro osteogenic effects of the materials were studied by focal adhesion, MTS,
      and alizarin red. Micro-CT analysis indicated that the DECBM and the HGCS
      scaffold groups developed greater radiopaque areas than the other groups. Bone
      regeneration, assessed using histological analysis and fluorochrome labeling, was
      the highest in the HGCS scaffold seeded with MAPCs. The DECBM group showed
      limited osteoinductivity, causing a gap between the implant and host tissue. The
      group grafted with HGCS+MAPCs resulting in twice as much new bone formation seems
      to indicate a role for effective bone regeneration. In conclusion, the novel HGCS
      scaffold could improve bone regeneration and is a promising carrier for stem cell
      mediated bone regeneration.

PMID- 25054150
TI  - High-level antimicrobial efficacy of representative Mediterranean natural plant
      extracts against oral microorganisms.
AB  - Nature is an unexplored reservoir of novel phytopharmaceuticals. Since biofilm
      related oral diseases often correlate with antibiotic resistance, plant-derived
      antimicrobial agents could enhance existing treatment options. Therefore, the
      rationale of the present report was to examine the antimicrobial impact of
      Mediterranean natural extracts on oral microorganisms. Five different extracts
      from Olea europaea, mastic gum, and Inula viscosa were tested against ten
      bacteria and one Candida albicans strain. The extraction protocols were conducted
      according to established experimental procedures. Two antimicrobial assays--the
      minimum inhibitory concentration (MIC) assay and the minimum bactericidal
      concentration (MBC) assay--were applied. The screened extracts were found to be
      active against each of the tested microorganisms. O. europaea presented MIC and
      MBC ranges of 0.07-10.00 mg mL(-1) and 0.60-10.00 mg mL(-1), respectively. The
      mean MBC values for mastic gum and I. viscosa were 0.07-10.00 mg mL(-1) and 0.15
      10.00 mg mL(-1), respectively. Extracts were less effective against C. albicans
      and exerted bactericidal effects at a concentration range of 0.07-5.00 mg mL(-1)
      on strict anaerobic bacteria (Porphyromonas gingivalis, Prevotella intermedia,
      Fusobacterium nucleatum, and Parvimonas micra). Ethyl acetate I. viscosa extract
      and total mastic extract showed considerable antimicrobial activity against oral
      microorganisms and could therefore be considered as alternative natural anti
      infectious agents.

PMID- 25054151
TI  - Value of histopathologic examination of uterine products after first-trimester
      miscarriage.
AB  - The main rationale of routine histopathologic examination of products after first
      trimester miscarriages is to detect an ectopic pregnancy or a molar pregnancy,
      which require further management. An alternative approach is to examine the
      products only when there is a definite indication. As there is no agreement, we
      aimed to study whether routine histopathological examination of tissues obtained
      after first-trimester miscarriage is of any clinical value in our populations.
      Medical records of all (558) patients with a diagnosis of first-trimester
      miscarriage over 4 years (2007-2010) at King Abdulaziz University Hospital,
      Jeddah, Saudi Arabia, were reviewed. Histopathologic examination confirmed
      products of conception in 537 (96.2%) patients, no products of conception in 17
      (3%) patients, molar pregnancy in 2 (0.4%) patients, and decidual tissues without
      chorionic villi (Arias-Stella reaction) in 2 (0.4%) patients. After clinical
      correlation, only one unsuspected partial molar pregnancy was diagnosed by
      histopathology examination. Conclusion is that it does not appear reasonable to
      perform histopathological examination routinely after all first-trimester
      miscarriages in our studied population. We recommend that histopathological
      examination be performed in select instances: when the diagnosis is uncertain,
      when fewer tissues have been obtained during surgery, when unexpected pathology
      was seen, when ultrasound suggests a molar pregnancy, or when patients are
      considered at high risk for trophoblastic disease. 

PMID- 25054152
TI  - CELLCOUNTER: novel open-source software for counting cell migration and invasion
      in vitro.
AB  - Transwell Boyden chamber based migration/invasion assay is a simple and
      extensively used approach for the characterization of cell motility in vitro.
      Cell motility is quantified by counting the number of cells that pass through the
      filter membrane. The counting is usually performed manually, which is laborious
      and error prone. We have therefore developed CELLCOUNTER, an application that is
      capable of recognizing and counting the total number of cells through an
      intuitive graphical user interface. The counting can be performed in batch, and
      the counting results can be visualized and further curated manually. CELLCOUNTER
      will be helpful in streamlining the experimental process and improving the
      reliability of the data acquisition. 

PMID- 25054153
TI  - Dissecting the role of bone marrow stromal cells on bone metastases.
AB  - Tumor-induced bone disease is a dynamic process that involves interactions with
      many cell types. Once metastatic cancer cells reach the bone, they are in contact
      with many different cell types that are present in the cell-rich bone marrow.
      These cells include the immune cells, myeloid cells, fibroblasts, osteoblasts,
      osteoclasts, and mesenchymal stem cells. Each of these cell populations can
      influence the behavior or gene expression of both the tumor cells and the bone
      microenvironment. Additionally, the tumor itself can alter the behavior of these
      bone marrow cells which further alters both the microenvironment and the tumor
      cells. While many groups focus on studying these interactions, much remains
      unknown. A better understanding of the interactions between the tumor cells and
      the bone microenvironment will improve our knowledge on how tumors establish in
      bone and may lead to improvements in diagnosing and treating bone metastases.
      This review details our current knowledge on the interactions between tumor cells
      that reside in bone and their microenvironment. 

PMID- 25054154
TI  - Integrating in silico prediction methods, molecular docking, and molecular
      dynamics simulation to predict the impact of ALK missense mutations in structural
      perspective.
AB  - Over the past decade, advancements in next generation sequencing technology have
      placed personalized genomic medicine upon horizon. Understanding the likelihood
      of disease causing mutations in complex diseases as pathogenic or neutral remains
      as a major task and even impossible in the structural context because of its time
      consuming and expensive experiments. Among the various diseases causing
      mutations, single nucleotide polymorphisms (SNPs) play a vital role in defining
      individual's susceptibility to disease and drug response. Understanding the
      genotype-phenotype relationship through SNPs is the first and most important step
      in drug research and development. Detailed understanding of the effect of SNPs on
      patient drug response is a key factor in the establishment of personalized
      medicine. In this paper, we represent a computational pipeline in anaplastic
      lymphoma kinase (ALK) for SNP-centred study by the application of in silico
      prediction methods, molecular docking, and molecular dynamics simulation
      approaches. Combination of computational methods provides a way in understanding
      the impact of deleterious mutations in altering the protein drug targets and
      eventually leading to variable patient's drug response. We hope this rapid and
      cost effective pipeline will also serve as a bridge to connect the clinicians and
      in silico resources in tailoring treatments to the patients' specific genotype. 

PMID- 25054155
TI  - Trichinella spiralis excretory-secretory products protect against polymicrobial
      sepsis by suppressing MyD88 via mannose receptor.
AB  - Trichinella spiralis (T. spiralis) or its excretory-secretory products (TsES)
      protect hosts from autoimmune diseases, which depend on inducing host T helper
      (Th) 2 immune response and inhibiting inflammatory factors. Sepsis is a systemic
      inflammatory response syndrome (SIRS) evoked by infection. Little is known about
      the effects of helminths or their excretory-secretory products on sepsis. Here,
      we investigated the effects of TsES in a mice model of polymicrobial sepsis. TsES
      improved survival, reduced organ injury, and enhanced bacterial clearance in
      septic mice. To investigate the molecular mechanism, macrophages from septic
      patients or the control group were incubated with TsES. TsES reduced sepsis
      inducing inflammatory cytokines mediated by Toll-like receptors (TLR) in vitro by
      suppressing TLR adaptor-transducer myeloid differentiation factor 88 (MyD88) and
      nuclear factor- (NF-)-kappaB. Furthermore, TsES upregulated mannose receptor (MR)
      expression during sepsis. MR blocking attenuated the effects of TsES on MyD88 and
      NF-kappaB expression. In vivo, MR RNAi reduced the survival rate of septic mice
      treated with TsES, suggesting that TsES-mediated protection against polymicrobial
      sepsis is dependent on MR. Thus, TsES administration might be a potential
      therapeutic strategy for treating sepsis.

PMID- 25054156
TI  - Muscle-type specific autophosphorylation of CaMKII isoforms after paced
      contractions.
AB  - We explored to what extent isoforms of the regulator of excitation-contraction
      and excitation-transcription coupling, calcium/calmodulin protein kinase II
      (CaMKII) contribute to the specificity of myocellular calcium sensing between
      muscle types and whether concentration transients in its autophosphorylation can
      be simulated. CaMKII autophosphorylation at Thr287 was assessed in three muscle
      compartments of the rat after slow or fast motor unit-type stimulation and was
      compared against a computational model (CaMuZclE) coupling myocellular calcium
      dynamics with CaMKII Thr287 phosphorylation. Qualitative differences existed
      between fast- (gastrocnemius medialis) and slow-type muscle (soleus) for the
      expression pattern of CaMKII isoforms. Phospho-Thr287 content of deltaA CaMKII,
      associated with nuclear functions, demonstrated a transient and compartment
      specific increase after excitation, which contrasted to the delayed
      autophosphorylation of the sarcoplasmic reticulum-associated betaM CaMKII. In
      soleus muscle, excitation-induced deltaA CaMKII autophosphorylation demonstrated
      frequency dependence (P = 0.02). In the glycolytic compartment of gastrocnemius
      medialis, CaMKII autophosphorylation after excitation was blunted. In silico
      assessment emphasized the importance of mitochondrial calcium buffer capacity for
      excitation-induced CaMKII autophosphorylation but did not predict its isoform
      specificity. The findings expose that CaMKII autophosphorylation with paced
      contractions is regulated in an isoform and muscle type-specific fashion and
      highlight properties emerging for phenotype-specific regulation of CaMKII. 

PMID- 25054158
TI  - Dose-response-relationship between number of laser burns and IOP reduction in
      cyclophotocoagulation: an animal study.
AB  - PURPOSE: The relationship between number of laser burns of cyclophotocoagulation
      (CPC) and intraocular pressure (IOP) reduction is unknown. This animal model was
      established to reveal a possible dose-response-relationship between the number of
      applied laser burns and the IOP lowering effect. METHODS: 30 chinchilla bastard
      rabbits were divided into 5 groups and treated with either 1, 5, 10, 20, or 30
      CPC burns, respectively. IOP was followed up for 1 week. IOP reduction of a
      single 30-burn treatment was compared with a fractionated treatment (three
      sessions; one week in between; 10 burns/session). RESULTS: IOP reduction
      increases nonlinearly with the number of CPC burns (max. -6.1 +/- 1.4 mmHg).
      Fractionated treatment shows similar IOP reduction with less complications and
      more constant results compared to single session treatment. CONCLUSIONS: The
      study reveals a complex relationship between IOP reduction and the number of CPC
      burns. Fractionated CPC gives comparable IOP reduction at a higher degree of
      safety.

PMID- 25054157
TI  - Stem cell transplantation for muscular dystrophy: the challenge of immune
      response.
AB  - Treating muscle disorders poses several challenges to the rapidly evolving field
      of regenerative medicine. Considerable progress has been made in isolating,
      characterizing, and expanding myogenic stem cells and, although we are now
      envisaging strategies to generate very large numbers of transplantable cells
      (e.g., by differentiating induced pluripotent stem cells), limitations directly
      linked to the interaction between transplanted cells and the host will continue
      to hamper a successful outcome. Among these limitations, host inflammatory and
      immune responses challenge the critical phases after cell delivery, including
      engraftment, migration, and differentiation. Therefore, it is key to study the
      mechanisms and dynamics that impair the efficacy of cell transplants in order to
      develop strategies that can ultimately improve the outcome of allogeneic and
      autologous stem cell therapies, in particular for severe disease such as muscular
      dystrophies. In this review we provide an overview of the main players and issues
      involved in this process and discuss potential approaches that might be
      beneficial for future regenerative therapies of skeletal muscle. 

PMID- 25054159
TI  - Cardiomyopathy in offspring of pregestational diabetic mouse pregnancy.
AB  - PURPOSE: To investigate cardiomyopathy in offspring in a mouse model of
      pregestational type 1 diabetic pregnancy. METHODS: Pregestational diabetes was
      induced with STZ administration in female C57BL6/J mice that were subsequently
      mated with healthy C57BL6/J males. Offspring were sacrificed at embryonic day
      18.5 and 6-week adolescent and 12-week adult stages. The size and number of
      cardiomyocyte nuclei and also the extent of collagen deposition within the hearts
      of diabetic and control offspring were assessed following cardiac tissue staining
      with either haematoxylin and eosin or Picrosirius red and subsequently quantified
      using automated digital image analysis. RESULTS: Offspring from diabetic mice at
      embryonic day 18.5 had a significantly higher number of cardiomyocyte nuclei
      present compared to controls. These nuclei were also significantly smaller than
      controls. Collagen deposition was shown to be significantly increased in the
      hearts of diabetic offspring at the same age. No significant differences were
      found between the groups at 6 and 12 weeks. CONCLUSIONS: Our results from
      offspring of type 1 diabetic mice show increased myocardial collagen deposition
      in late gestation and have increased myocardial nuclear counts (hyperplasia) as
      opposed to increased myocardial nuclear size (hypertrophy) in late gestation.
      These changes normalize postpartum after removal from the maternal intrauterine
      environment.

PMID- 25054160
TI  - The effect of chromium picolinate supplementation on the pancreas and
      macroangiopathy in type II diabetes mellitus rats.
AB  - PURPOSE: The aim was to explore the effect of the chromium picolinate (CrPic)
      administration on the pancreas and macroangiopathy of type II diabetes mellitus
      rats. METHODS: The type II diabetes mellitus (T2DM) rat model was induced by low
      dose streptozotocin (STZ). The rats were randomly divided into 5 groups (ten rats
      in each group). After supplementing CrPic for 15 weeks, the histopathological
      examination was performed by hematoxylin-eosin (HE) staining. Serum insulin and
      NO level were determined by radioimmunoassay and colorimetry, respectively. Serum
      glycosylated hemoglobin (HbA1C), adiponectin (APN), advanced glycation end
      products (AGES), and apelin were measured by ELISA. Real-time reverse
      transcription polymerase chain reaction (RT-PCR) was applied for detecting the
      mRNA expression of APN and apelin. RESULTS: After CrPic treatment, compared with
      the T2DM control group (group 2), pancreas sections stained with HE showed the
      completed pancreatic cells structure and no inflammatory infiltration in groups 4
      and 5. In addition, the levels of serum NO and insulin were significantly
      increased and the serum levels of HbA1C, AGES, APN, and apelin were significantly
      decreased in groups 4 and 5 compared with group 2. The mRNA expression of APN and
      apelin in groups 4 and 5 was also recovered to the normal level. CONCLUSION:
      CrPic can recover the function of Beta-cells and alleviate macroangiopathy in STZ
      induced T2DM rats.

PMID- 25054162
TI  - First- and second-order full-differential in edge analysis of images.
AB  - Two concepts of first- and second-order differential of images are presented to
      deal with the changes of pixels. These are the basic ideas in mathematics. We
      propose and reformulate them with a uniform definition framework. Based on our
      observation and analysis with the difference, we propose an algorithm to detect
      the edge from image. Experiments on Corel5K and PASCAL VOC 2007 are done to show
      the difference between the first order and the second order. After comparison
      with Canny operator and the proposed first-order differential, the main result is
      that the second-order differential has the better performance in analysis of
      changes of the context of images with good selection of control parameter. 

PMID- 25054161
TI  - Role of lysosomes in silica-induced inflammasome activation and inflammation in
      absence of MARCO.
AB  - MARCO is the predominant scavenger receptor for recognition and binding of silica
      particles by alveolar macrophages (AM). Previously, it was shown that mice null
      for MARCO have a greater inflammatory response to silica, but the mechanism was
      not described. The aim of this study was to determine the relationship between
      MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome
      activation and release of the proinflammatory cytokine, IL-1beta, to a greater
      extent in MARCO(-/-) AM compared to wild type (WT) AM. Furthermore, in MARCO(-/-)
      AM there was greater cathepsin B release from phagolysosomes, Caspase-1
      activation, and acid sphingomyelinase activity compared to WT AM, supporting the
      critical role played by lysosomal membrane permeabilization (LMP) in triggering
      silica-induced inflammation. The difference in sensitivity to LMP appears to be
      in cholesterol recycling since increasing cholesterol in AM by treatment with
      U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking
      MARCO were less able to sequester cholesterol following silica treatment. Taken
      together, these results demonstrate that MARCO contributes to normal cholesterol
      uptake in macrophages; therefore, in the absence of MARCO, macrophages are more
      susceptible to a greater inflammatory response by particulates known to cause
      NLRP3 inflammasome activation and the effect is due to increased LMP. 

PMID- 25054163
TI  - Smart HVAC control in IoT: energy consumption minimization with user comfort
      constraints.
AB  - Smart grid is one of the main applications of the Internet of Things (IoT)
      paradigm. Within this context, this paper addresses the efficient energy
      consumption management of heating, ventilation, and air conditioning (HVAC)
      systems in smart grids with variable energy price. To that end, first, we propose
      an energy scheduling method that minimizes the energy consumption cost for a
      particular time interval, taking into account the energy price and a set of
      comfort constraints, that is, a range of temperatures according to user's
      preferences for a given room. Then, we propose an energy scheduler where the user
      may select to relax the temperature constraints to save more energy. Moreover,
      thanks to the IoT paradigm, the user may interact remotely with the HVAC control
      system. In particular, the user may decide remotely the temperature of comfort,
      while the temperature and energy consumption information is sent through Internet
      and displayed at the end user's device. The proposed algorithms have been
      implemented in a real testbed, highlighting the potential gains that can be
      achieved in terms of both energy and cost. 

PMID- 25054164
TI  - Balteatide: a novel antimicrobial decapeptide from the skin secretion of the
      purple-sided leaf frog, Phyllomedusa baltea.
AB  - The skin secretions of Neotropical phyllomedusine leaf frogs have proven to be a
      rich source of biologically active peptides, including antimicrobials. The major
      families of antimicrobial peptides (AMPs) reported are the dermaseptins and
      phylloseptins and the minor families are the dermatoxins, phylloxins, plasticins,
      distinctins, and medusins. Here, we report a novel AMP of 10 amino acid residues
      (LRPAILVRIKamide), named balteatide, from the skin secretion of wild Peruvian
      purple-sided leaf frogs, Phyllomedusa baltea. Balteatide was found to exhibit a
      90% sequence identity with sauvatide, a potent myotropic peptide from the skin
      secretion of Phyllomedusa sauvagei. However, despite both peptides exhibiting
      only a single amino acid difference (I/T at position 9), sauvatide is devoid of
      antimicrobial activity and balteatide is devoid of myotropic activity. Balteatide
      was found to have differential activity against the Gram-positive bacterium,
      Staphylococcus aureus; the Gram-negative bacterium, Escherichia coli; and the
      yeast, Candida albicans, and unusual for phyllomedusine frog skin AMPs, was most
      potent (MIC 32 mg/L) against the yeast. Balteatide was also devoid of haemolytic
      activity up to concentrations of 512 mg/L. Phyllomedusine frog skin secretions
      thus continue to provide novel AMPs, some of which may provide templates for the
      rational design of new classes of anti-infective therapeutics. 

PMID- 25054165
TI  - Health risks faced by Turkish agricultural workers.
AB  - BACKGROUND: Individuals who make a living through agriculture and animal
      husbandry are faced with a variety of physical and psychological health risks. In
      many international studies, it has been shown that these risks can result in
      disease. The purpose of this study is to summarize the health risks faced by
      Turkish agricultural workers. MATERIALS AND METHODS: This study used a nonrandom,
      convenience sample. The biopsychosocial health statuses of 177 farmers from 11
      central villages in Kars, Turkey, were examined. RESULTS: It was determined that
      the depression rate among the study group was 62.1%, the rate of physical health
      problems was 52.0%, and the rate of social isolation was 53.7%. There was a
      statistically significant difference between the depression scale scores and
      lower education levels, having >= three children, and physical health problems,
      as well as the physical condition of the farmers' homes. There was a significant
      difference between poor physical health and older age, lower education levels,
      having >= three children, and social isolation. CONCLUSIONS: In providing data
      based evidence, it is believed that this study will contribute considerably to
      understanding the causality of health problems in this population and in planning
      the development of public health and veterinary services based on regional needs.

PMID- 25054166
TI  - Induction of resistance mediated by an attenuated strain of Valsa mali var. mali
      using pathogen-apple callus interaction system.
AB  - To study the induced resistance in apple against Valsa mali var. mali (Vmm), a
      Vmm-apple callus interaction system was developed to evaluate the induced
      resistance of an attenuated Vmm strain LXS081501 against further infection by a
      virulent Vmm strain LXS080601. The infection index was up to 97.32 for apple
      calli inoculated with LXS080601 alone at 15 days after inoculation whereas it was
      only 41.84 for calli pretreated with LXS081501 followed by LXS080601 inoculation.
      In addition, the maximum levels of free proline, soluble sugar, and protein in
      calli treated with LXS081501 plus LXS080601 were 2.14 to 3.47 times higher than
      controls and 1.42 to 1.75 times higher than LXS080601 treatment. The activities
      of defense-related enzymes such as phenylalanine ammonia lyase (PAL), polyphenol
      oxidase (PPO), peroxidase (POD), and catalase (CAT) as well as beta-1,3-glucanase
      and chitinase in apple calli inoculated with LXS080601 alone or LXS081501 plus
      LXS080601 increased significantly 24 hai and peaked from 48 to 120 hpi. However,
      in the latter treatment, the maximum enzyme activities were much higher and the
      activities always maintained much higher levels than control during the
      experimental period. These results suggested the roles of osmotic adjustment
      substances and defense-related enzymes in induced resistance. 

PMID- 25054167
TI  - The reproducibility of indoor air pollution (IAP) measurement: a test case for
      the measurement of key air pollutants from the pan frying of fish samples.
AB  - To assess the robustness of various indoor air quality (IAQ) indices, we explored
      the possible role of reproducibility-induced variability in the measurements of
      different pollutants under similar sampling and emissions conditions. Polluted
      indoor conditions were generated by pan frying fish samples in a closed room. A
      total of 11 experiments were carried out to measure a list of key variables
      commonly used to represent indoor air pollution (IAP) indicators such as
      particulate matter (PM: PM1, PM2.5, PM10, and TSP) and a set of individual
      volatile organic compounds (VOCs) with some odor markers. The cooking activity
      conducted as part of our experiments was successful to consistently generate
      significant pollution levels (mean PM10: 7110 MUg m(-3) and mean total VOC
      (TVOC): 1400 MUg m(-3), resp.). Then, relative standard error (RSE) was computed
      to assess the reproducibility between different IAP paramters measured across the
      repeated experiments. If the results were evaluated by an arbitrary criterion of
      10%, the patterns were divided into two data groups (e.g., <10% for benzene and
      some aldehydes and >10% for the remainders). Most noticeably, TVOC had the most
      repeatable results with a reproducibility (RSE) value of 3.2% (n = 11). 

PMID- 25054168
TI  - Recent development in partial differential equations and their applications.

PMID- 25054169
TI  - Path planning method for UUV homing and docking in movement disorders
      environment.
AB  - Path planning method for unmanned underwater vehicles (UUV) homing and docking in
      movement disorders environment is proposed in this paper. Firstly, cost function
      is proposed for path planning. Then, a novel particle swarm optimization (NPSO)
      is proposed and applied to find the waypoint with minimum value of cost function.
      Then, a strategy for UUV enters into the mother vessel with a fixed angle being
      proposed. Finally, the test function is introduced to analyze the performance of
      NPSO and compare with basic particle swarm optimization (BPSO), inertia weight
      particle swarm optimization (LWPSO, EPSO), and time-varying acceleration
      coefficient (TVAC). It has turned out that, for unimodal functions, NPSO
      performed better searching accuracy and stability than other algorithms, and, for
      multimodal functions, the performance of NPSO is similar to TVAC. Then, the
      simulation of UUV path planning is presented, and it showed that, with the
      strategy proposed in this paper, UUV can dodge obstacles and threats, and search
      for the efficiency path. 

PMID- 25054171
TI  - Real-time hand gesture recognition using finger segmentation.
AB  - Hand gesture recognition is very significant for human-computer interaction. In
      this work, we present a novel real-time method for hand gesture recognition. In
      our framework, the hand region is extracted from the background with the
      background subtraction method. Then, the palm and fingers are segmented so as to
      detect and recognize the fingers. Finally, a rule classifier is applied to
      predict the labels of hand gestures. The experiments on the data set of 1300
      images show that our method performs well and is highly efficient. Moreover, our
      method shows better performance than a state-of-art method on another data set of
      hand gestures. 

PMID- 25054170
TI  - A quantitative method for the characterization of lytic metastases of the bone
      from radiographic images.
AB  - The aim of our study was to assess the diagnostic usefulness of the gray level
      parameters to distinguish osteolytic lesions using radiological images. Materials
      and Methods. A retrospective study was carried out. A total of 76 skeletal
      radiographs of osteolytic metastases and 67 radiographs of multiple myeloma were
      used. The cases were classified into nonflat (MM1 and OL1) and flat bones (MM2
      and OL2). These radiological images were analyzed by using a computerized method.
      The parameters calculated were mean, standard deviation, and coefficient of
      variation (MGL, SDGL, and CVGL) based on gray level histogram analysis of a
      region-of-interest. Diagnostic utility was quantified by measurement of
      parameters on osteolytic metastases and multiple myeloma, yielding quantification
      of area under the receiver operating characteristic (ROC) curve (AUC). Results.
      Flat bone groups (MM2 and OL2) showed significant differences in mean values of
      MGL (P = 0.048) and SDGL (P = 0.003). Their corresponding values of AUC were
      0.758 for MGL and 0.883 for SDGL in flat bones. In nonflat bones these gray level
      parameters do not show diagnostic ability. Conclusion. The gray level parameters
      MGL and SDGL show a good discriminatory diagnostic ability to distinguish between
      multiple myeloma and lytic metastases in flat bones. 

PMID- 25054172
TI  - Numerical analysis of modeling based on improved Elman neural network.
AB  - A modeling based on the improved Elman neural network (IENN) is proposed to
      analyze the nonlinear circuits with the memory effect. The hidden layer neurons
      are activated by a group of Chebyshev orthogonal basis functions instead of
      sigmoid functions in this model. The error curves of the sum of squared error
      (SSE) varying with the number of hidden neurons and the iteration step are
      studied to determine the number of the hidden layer neurons. Simulation results
      of the half-bridge class-D power amplifier (CDPA) with two-tone signal and
      broadband signals as input have shown that the proposed behavioral modeling can
      reconstruct the system of CDPAs accurately and depict the memory effect of CDPAs
      well. Compared with Volterra-Laguerre (VL) model, Chebyshev neural network (CNN)
      model, and basic Elman neural network (BENN) model, the proposed model has better
      performance. 

PMID- 25054173
TI  - Impact of heat and mass transfer during the transport of nitrogen in coal porous
      media on coal mine fires.
AB  - The application of liquid nitrogen injection is an important technique in the
      field of coal mine fire prevention. However, the mechanism of heat and mass
      transfer of cryogenic nitrogen in the goaf porous medium has not been well
      accessed. Hence, the implementation of fire prevention engineering of liquid
      nitrogen roughly relied on an empirical view. According to the research gap in
      this respect, an experimental study on the heat and mass transfer of liquid
      nitrogen in coal porous media was proposed. Overall, the main mechanism of liquid
      nitrogen fire prevention technology in the coal mine is the creation of an inert
      and cryogenic atmosphere. Cryogenic nitrogen gas vapor cloud, heavier than the
      air, would cause the phenomenon of "gravity settling" in porous media firstly.
      The cryogen could be applicable to diverse types of fires, both in the openings
      and in the enclosures. Implementation of liquid nitrogen open-injection technique
      in Yangchangwan colliery achieved the goals of fire prevention and air-cooling.
      Meanwhile, this study can also provide an essential reference for the research on
      heat and mass transfer in porous media in the field of thermal physics and
      engineering. 

PMID- 25054174
TI  - A grey NGM(1,1, k) self-memory coupling prediction model for energy consumption
      prediction.
AB  - Energy consumption prediction is an important issue for governments, energy
      sector investors, and other related corporations. Although there are several
      prediction techniques, selection of the most appropriate technique is of vital
      importance. As for the approximate nonhomogeneous exponential data sequence often
      emerging in the energy system, a novel grey NGM(1,1, k) self-memory coupling
      prediction model is put forward in order to promote the predictive performance.
      It achieves organic integration of the self-memory principle of dynamic system
      and grey NGM(1,1, k) model. The traditional grey model's weakness as being
      sensitive to initial value can be overcome by the self-memory principle. In this
      study, total energy, coal, and electricity consumption of China is adopted for
      demonstration by using the proposed coupling prediction technique. The results
      show the superiority of NGM(1,1, k) self-memory coupling prediction model when
      compared with the results from the literature. Its excellent prediction
      performance lies in that the proposed coupling model can take full advantage of
      the systematic multitime historical data and catch the stochastic fluctuation
      tendency. This work also makes a significant contribution to the enrichment of
      grey prediction theory and the extension of its application span. 

PMID- 25054175
TI  - Motivators for physical activity among ambulatory nursing home older residents.
AB  - The purpose of this study was to explore self-identified motivators for regular
      physical activity among ambulatory nursing home older residents. A qualitative
      exploratory design was adopted. Purposive sampling was performed to recruit 18
      older residents from two nursing homes in Taiwan. The interview transcripts were
      analyzed by qualitative content analysis. Five motivators of physical activity
      emerged from the result of analysis: eagerness for returning home, fear of
      becoming totally dependent, improving mood state, filling empty time, and
      previously cultivated habit. Research on physical activity from the perspectives
      of nursing home older residents has been limited. An empirically grounded
      understanding from this study could provide clues for promoting and supporting
      lifelong engagement in physical activity among older residents. The motivators
      reported in this study should be considered when designing physical activity
      programs. These motivators can be used to encourage, guide, and provide feedback
      to support older residents in maintaining physical activity. 

PMID- 25054176
TI  - Numerical investigation of galloping instabilities in Z-shaped profiles.
AB  - Aeroelastic effects are relatively common in the design of modern civil
      constructions such as office blocks, airport terminal buildings, and factories.
      Typical flexible structures exposed to the action of wind are shading devices,
      normally slats or louvers. A typical cross-section for such elements is a Z
      shaped profile, made out of a central web and two-side wings. Galloping
      instabilities are often determined in practice using the Glauert-Den Hartog
      criterion. This criterion relies on accurate predictions of the dependence of the
      aerodynamic force coefficients with the angle of attack. The results of a
      parametric analysis based on a numerical analysis and performed on different Z
      shaped louvers to determine translational galloping instability regions are
      presented in this paper. These numerical analysis results have been validated
      with a parametric analysis of Z-shaped profiles based on static wind tunnel
      tests. In order to perform this validation, the DLR TAU Code, which is a standard
      code within the European aeronautical industry, has been used. This study
      highlights the focus on the numerical prediction of the effect of galloping,
      which is shown in a visible way, through stability maps. Comparisons between
      numerical and experimental data are presented with respect to various meshes and
      turbulence models. 

PMID- 25054177
TI  - Production and purification of a novel xanthan lyase from a xanthan-degrading
      Microbacterium sp. strain XT11.
AB  - A xanthan lyase was produced and purified from the culture supernatant of an
      excellent xanthan-modifying strain Microbacterium sp. XT11. Xanthan lyase was
      induced by xanthan but was inhibited by its structural monomer glucose. Its
      production by strain XT11 is much higher than that by all other reported strains.
      The purified xanthan lyase has a molecular mass of 110 kDa and a specific
      activity of 28.2 U/mg that was much higher than that of both Paenibacillus and
      Bacillus lyases. It was specific on the pyruvated mannosyl residue in the intact
      xanthan molecule, but about 50% lyase activity remained when xanthan was
      partially depyruvated. Xanthan lyase was optimally active at pH 6.0-6.5 and 40
      degrees C and alkali-tolerant at a high pH value of 11.0. The metal ions
      including K(+), Ca(2+), Na(+), Mg(2+), Mn(2+), and Li(+) strongly stimulated
      xanthan lyase activity but ions Zn(2+) and Cu(2+) were its inhibitor. Xanthan
      lyase should be a novel enzyme different from the other xanthan lyases ever
      reported. 

PMID- 25054178
TI  - Silicon application increases drought tolerance of kentucky bluegrass by
      improving plant water relations and morphophysiological functions.
AB  - Drought stress encumbers the growth of turfgrass principally by disrupting the
      plant-water relations and physiological functions. The present study was carried
      out to appraise the role of silicon (Si) in improving the drought tolerance in
      Kentucky bluegrass (Poa pratensis L.). Drought stress and four levels (0, 200,
      400, and 800 mg L(-1)) of Si (Na2SiO3.9H2O) were imposed after 2 months old
      plants cultured under glasshouse conditions. Drought stress was found to decrease
      the photosynthesis, transpiration rate, stomatal conductance, leaf water content,
      relative growth rate, water use efficiency, and turf quality, but to increase in
      the root/shoot and leaf carbon/nitrogen ratio. Such physiological interferences,
      disturbances in plant water relations, and visually noticeable growth reductions
      in Kentucky bluegrass were significantly alleviated by the addition of Si after
      drought stress. For example, Si application at 400 mg L(-1) significantly
      increased the net photosynthesis by 44%, leaf water contents by 33%, leaf green
      color by 42%, and turf quality by 44% after 20 days of drought stress. Si
      application proved beneficial in improving the performance of Kentucky bluegrass
      in the present study suggesting that manipulation of endogenous Si through
      genetic or biotechnological means may result in the development of drought
      resistance in grasses. 

PMID- 25054179
TI  - Facile preparation of carbon microcapsules containing phase-change material with
      enhanced thermal properties.
AB  - This study describes the hydrothermal synthesis of a novel carbon/palmitic acid
      (PA) microencapsulated phase change material (MEPCM). The field emission scanning
      electron microscopy (FESEM) and high resolution transmission electron microscopy
      (HRTEM) images confirm that spherical capsules of uniform size were formed with a
      mean diameter of 6.42 MUm. The melting and freezing temperature were found to be
      slightly lower than those of pure PA with little undercooling. The composite
      retained 75% of the latent heat of pure PA. Thermal stability of the MEPCM was
      found to be better than that of pure PA. The thermal conductivity of MEPCM was
      increased by as much as 41% at 30 degrees C. Due to its good thermal properties
      and chemical and mechanical stability, the carbon/PA MEPCM displays a good
      potential for thermal energy storage systems. 

PMID- 25054180
TI  - Growth and comprehensive quality index of tomato under rain shelters in response
      to different irrigation and drainage treatments.
AB  - The effects of two levels of irrigation water (100%, 60%) and buried underground
      pipe depths (0.8 m, 0.6 m) under rain shelters' conditions on yield and some
      quality parameters of tomato were investigated. A fully randomized factorial
      experiment was conducted between April and August in 2011 and 2012 at Hohai
      University. It was found that drainage treatments enhanced biomass production,
      whereas soil desiccation led to biomass reduction. At 60 cm buried underground
      pipe depths, the drought treatments increased the mean root weight and root-shoot
      ratio by 14% and 39%, respectively. The main effects of drainage treatments on
      the fruit quality were increases in total soluble solids (TSS), soluble sugar
      (SS), and vitamin C (VC) compared to the control. In addition, drainage
      treatments increased the average yield by 13% and 9%, respectively, in both
      years. The drought treatments did not significantly alter fruit yield, although
      mean single fruit weight was slightly reduced. Instead, these treatments tend to
      have great potential to improve fruit quality (TSS, SS, and VC) to variable
      extents. In both years, the drought treatment at 60 cm buried underground pipe
      depths proved to possess the highest comprehensive quality index based on
      Principal Component Analysis. 

PMID- 25054181
TI  - An emergency packet forwarding scheme for V2V communication networks.
AB  - This paper proposes an effective warning message forwarding scheme for
      cooperative collision avoidance. In an emergency situation, an emergency
      detecting vehicle warns the neighbor vehicles via an emergency warning message.
      Since the transmission range is limited, the warning message is broadcast in a
      multihop manner. Broadcast packets lead two challenges to forward the warning
      message in the vehicular network: redundancy of warning messages and competition
      with nonemergency transmissions. In this paper, we study and address the two
      major challenges to achieve low latency in delivery of the warning message. To
      reduce the intervehicle latency and end-to-end latency, which cause chain
      collisions, we propose a two-way intelligent broadcasting method with an
      adaptable distance-dependent backoff algorithm. Considering locations of
      vehicles, the proposed algorithm controls the broadcast of a warning message to
      reduce redundant EWM messages and adaptively chooses the contention window to
      compete with nonemergency transmission. Via simulations, we show that our
      proposed algorithm reduces the probability of rear-end crashes by 70% compared to
      previous algorithms by reducing the intervehicle delay. We also show that the end
      to-end propagation delay of the warning message is reduced by 55%. 

PMID- 25054182
TI  - Optimization of large-scale culture conditions for the production of cordycepin
      with Cordyceps militaris by liquid static culture.
AB  - Cordycepin is one of the most important bioactive compounds produced by species
      of Cordyceps sensu lato, but it is hard to produce large amounts of this
      substance in industrial production. In this work, single factor design, Plackett
      Burman design, and central composite design were employed to establish the key
      factors and identify optimal culture conditions which improved cordycepin
      production. Using these culture conditions, a maximum production of cordycepin
      was 2008.48 mg/L for 700 mL working volume in the 1000 mL glass jars and total
      content of cordycepin reached 1405.94 mg/bottle. This method provides an
      effective way for increasing the cordycepin production at a large scale. The
      strategies used in this study could have a wide application in other fermentation
      processes. 

PMID- 25054184
TI  - Optimal battery sizing in photovoltaic based distributed generation using
      enhanced opposition-based firefly algorithm for voltage rise mitigation.
AB  - This paper presents the application of enhanced opposition-based firefly
      algorithm in obtaining the optimal battery energy storage systems (BESS) sizing
      in photovoltaic generation integrated radial distribution network in order to
      mitigate the voltage rise problem. Initially, the performance of the original
      firefly algorithm is enhanced by utilizing the opposition-based learning and
      introducing inertia weight. After evaluating the performance of the enhanced
      opposition-based firefly algorithm (EOFA) with fifteen benchmark functions, it is
      then adopted to determine the optimal size for BESS. Two optimization processes
      are conducted where the first optimization aims to obtain the optimal battery
      output power on hourly basis and the second optimization aims to obtain the
      optimal BESS capacity by considering the state of charge constraint of BESS. The
      effectiveness of the proposed method is validated by applying the algorithm to
      the 69-bus distribution system and by comparing the performance of EOFA with
      conventional firefly algorithm and gravitational search algorithm. Results show
      that EOFA has the best performance comparatively in terms of mitigating the
      voltage rise problem. 

PMID- 25054183
TI  - Recent advances in heterogeneous photocatalytic decolorization of synthetic dyes.
AB  - During the process and operation of the dyes, the wastes produced were commonly
      found to contain organic and inorganic impurities leading to risks in the
      ecosystem and biodiversity with the resultant impact on the environment. Improper
      effluent disposal in aqueous ecosystems leads to reduction of sunlight
      penetration which in turn diminishes photosynthetic activity, resulting in acute
      toxic effects on the aquatic flora/fauna and dissolved oxygen concentration.
      Recently, photodegradation of various synthetic dyes has been studied in terms of
      their absorbance and the reduction of oxygen content by changes in the
      concentration of the dye. The advantages that make photocatalytic techniques
      superior to traditional methods are the ability to remove contaminates in the
      range of ppb, no generation of polycyclic compounds, higher speed, and lower
      cost. Semiconductor metal oxides, typically TiO2, ZnO, SnO, NiO, Cu2O, Fe3O4, and
      also CdS have been utilized as photocatalyst for their nontoxic nature, high
      photosensitivity, wide band gap and high stability. Various process parameters
      like photocatalyst dose, pH and initial dye concentrations have been varied and
      highlighted. Research focused on surface modification of semiconductors and mixed
      oxide semiconductors by doping them with noble metals (Pt, Pd, Au, and Ag) and
      organic matter (C, N, Cl, and F) showed enhanced dye degradation compared to
      corresponding native semiconductors. This paper reviews recent advances in
      heterogeneous photocatalytic decolorization for the removal of synthetic dyes
      from water and wastewater. Thus, the main core highlighted in this paper is the
      critical selection of semiconductors for photocatalysis based on the chemical,
      physical, and selective nature of the poisoning dyes. 

PMID- 25054185
TI  - QuadraPure-supported palladium nanocatalysts for microwave-promoted Suzuki cross
      coupling reaction under aerobic condition.
AB  - Cross-linked resin-captured palladium (XL-QPPd) was readily prepared by simple
      physical adsorption onto the high loading QuadraPure macroporous resin and a
      subsequent reduction process. To enhance the mechanical stability, entrapped
      palladium nanocatalysts were cross-linked with succinyl chloride. Both
      transmission electron microscopy images and X-ray diffraction analysis revealed
      that the palladium nanoparticles were well dispersed with diameters ranging in 4
      10 nm. The catalyst performed good catalytic activity in microwave-promoted
      Suzuki cross-coupling reactions in water under aerobic condition with mild
      condition by using various aryl halides and phenylboronic acid. In addition, the
      catalyst showed an excellent recyclability without significant loss of catalytic
      activity. 

PMID- 25054186
TI  - Rockburst disaster prediction of isolated coal pillar by electromagnetic
      radiation based on frictional effect.
AB  - Based on the understanding that charges generated during coal cracking are due to
      coal particle friction, a microstructure model was developed by considering four
      different variation laws of friction coefficient. Firstly, the frictional energy
      release of coal sample during uniaxial compressive tests was investigated and
      discussed. Then electromagnetic radiation method was used to predict the
      potential rockburst disaster in isolated coal pillar mining face, Muchengjian
      Colliery. The results indicate that the friction coefficient of coal particles
      decreases linearly with the increase of axial loading force. In predicting the
      strain-type rockburst, the high stress state of coal must be closely monitored.
      Field monitoring shows that electromagnetic radiation signal became abnormal
      before the occurrence of rockburst during isolated coal pillar mining.
      Furthermore, rockburst tends to occur at the early and ending stages of isolated
      coal pillar extraction. Mine-site investigation shows the occurrence zone of
      rockburst is consistent with the prediction, proving the reliability of the
      electromagnetic radiation method to predict strain-type rockburst disaster. 

PMID- 25054187
TI  - Modelling and laboratory studies on the adhesion fatigue performance for thin
      film asphalt and aggregate system.
AB  - Adhesion between asphalt and aggregate plays an important role in the performance
      of asphalt mixtures. A low-frequency adhesion fatigue test was proposed in this
      paper to study the effect of environment on the asphalt-aggregate adhesion
      system. The stress-based fatigue model had been utilized to describe the fatigue
      behavior of thin-film asphalt and aggregate system. The factors influencing the
      adhesion fatigue performance were also investigated. Experiment results show that
      asphalt has more important effect on the adhesion performance comparing with
      aggregate. Basalt, which is regarded as hydrophobic aggregates with low silica
      content, has better adhesion performance to asphalt binder when compared with
      granite. The effects of aging on the adhesion fatigue performance are different
      for PG64-22 and rubber asphalt. Long-term aging is found to reduce the adhesion
      fatigue lives for rubber asphalt and aggregate system, while the effect of long
      term aging for aggregate and PG64-22 binder system is positive. Generally the
      increased stress amplitude and test temperature could induce greater damage and
      lead to less fatigue lives for adhesion test system. 

PMID- 25054188
TI  - Enhancing business intelligence by means of suggestive reviews.
AB  - Appropriate identification and classification of online reviews to satisfy the
      needs of current and potential users pose a critical challenge for the business
      environment. This paper focuses on a specific kind of reviews: the suggestive
      type. Suggestions have a significant influence on both consumers' choices and
      designers' understanding and, hence, they are key for tasks such as brand
      positioning and social media marketing. The proposed approach consists of three
      main steps: (1) classify comparative and suggestive sentences; (2) categorize
      suggestive sentences into different types, either explicit or implicit locutions;
      (3) perform sentiment analysis on the classified reviews. A range of supervised
      machine learning approaches and feature sets are evaluated to tackle the problem
      of suggestive opinion mining. Experimental results for all three tasks are
      obtained on a dataset of mobile phone reviews and demonstrate that extending a
      bag-of-words representation with suggestive and comparative patterns is ideal for
      distinguishing suggestive sentences. In particular, it is observed that
      classifying suggestive sentences into implicit and explicit locutions works best
      when using a mixed sequential rule feature representation. Sentiment analysis
      achieves maximum performance when employing additional preprocessing in the form
      of negation handling and target masking, combined with sentiment lexicons. 

PMID- 25054189
TI  - miR-16-1 promotes the aberrant alpha-synuclein accumulation in parkinson disease
      via targeting heat shock protein 70.
AB  - There is striking evidence that heat shock protein 70 (Hsp70) negatively
      regulates alpha-synuclein aggregation, which plays a significant role in the
      formation and progression of Parkinson disease (PD). However, how the Hsp70 in
      neurons fails to prevent or even reverse alpha-synuclein aggregation and toxicity
      in PD still remains to be determined. In the present study, we constructed an
      alpha-synuclein-overexpressed human neuroblastoma cell line, SH-SY5Y-Syn, in
      which the blockage of Hsp70 promoted alpha-synuclein aggregation. And we also
      found that miR-16-1 downregulated Hsp70 and promoted alpha-synuclein aggregation
      in the SH-SY5Y-Syn cells. This study revealed a novel regulatory mechanism of
      Hsp70 expression, which might contribute to the PD development. 

PMID- 25054190
TI  - Managing distrust-induced risk with deposit in supply chain contract decisions.
AB  - This paper studies the trust issue in a two-echelon supply chain information
      sharing process. In a supply chain, the retailer reports the forecasted demand to
      the supplier. Traditionally, the supplier's trust in the retailer's reported
      information is based on the retailer's reputation. However, this paper considers
      that trust is random and is also affected by the reputation and the demand gap.
      The supplier and retailer have been shown to have different evaluations regarding
      the degree of trust. Furthermore, distrust is inherently linked to perceived
      risk. To mitigate perceived risk, a two-stage decision process with an unpayback
      deposit contract is proposed. At the first stage, the supplier and the retailer
      negotiate the deposit contract. At the second stage, a Stackelberg game is used
      to determine the retailer's reported demand and the supplier's production
      quantity. We show that the deposits from the retailer's and supplier's
      perspectives are different. When the retailer's reported demand is equal to the
      supplier's forecasted demand, the retailer's evaluation of the deposit is more
      than that of supplier's. When the retailer's reported demand is equal to the
      retailer's forecasted demand, the deposit from the retailer's perspective is at
      the lowest level. 

PMID- 25054191
TI  - Reply to Gao et al: Racial composition does not explain increasing class gaps in
      obesity.

PMID- 25054192
TI  - Reply to Namboodiri and Hussain Shuler: Analysis of scaling of neuronal
      activities in medial prefrontal cortex during interval timing.

PMID- 25054193
TI  - Cortical adaptation staging system: a new and simple staging for result
      evaluation of functioning free-muscle transplantation for facial reanimation.
AB  - BACKGROUND: Movement-associated cortical reorganization occurs in patients after
      functioning free-muscle transplantation (FFMT), which is reinnervated by
      different neurotizers. Aiming to evaluate the process of recovery of the
      reinnervated muscle, we defined the cortical reorganization into 5 stages. This
      staging system has been applied during the past 25 years at our center with great
      convenience and accessibility. METHODS: A standardized evaluation method for
      assessing the recovery after FFMT to reanimate the paralyzed face with at least a
      1-year follow-up was applied. The evaluation included the following 5 stages: no
      movement, dependent movement, independent movement, and spontaneous movement with
      and without involuntary movement. Reliability of this technique was assessed by 3
      examiners, who each evaluated the smiles of 30 unilateral facial paralysis
      patients 4 times, creating 360 sets of measurements. RESULTS: The intraclass
      correlation coefficients for interrater and intrarater reliability exceeded
      0.929, which is considered excellent and reliable. CONCLUSIONS: Chuang's Cortical
      Adaptation Staging System is simple, quick,and accurate in evaluating patients
      after FFMT reanimation of the paralyzed face with no additional tools.

PMID- 25054194
TI  - Ultrastructural characteristics of 5BrdU labeling retention cells including stem
      cells of regenerating feathers in chicken.
AB  - Feathers regenerate from stem cells localized in a region of the follicle
      indicated as the bulge of the collar. Stem cells are slow cycling cells and some
      of these cells can be identified after labeling experiments using 5-bromo
      deoxyuridine to detect label retaining cells (5BrdU LRCs). The present electron
      microscopic analysis of 5BrdU LRCs has described the ultrastructural
      characteristics of small cells present in the bulge region of the follicle in
      regenerating feathers of chickens that include stem cells. Labeled feather stem
      cells are smaller than 10 lm in average diameter, possess large nuclei with high
      nuclear/cytoplasmic ratio, and contain evenly distributed ribosomes, sparse
      bundles of intermediate filaments, scarce or no endoplasmic reticulum, and few
      mitochondria. The nuclei are mainly euchromatic with a variable amount of
      heterochromatin clumps and the nucleoli show developed granular and fibrillar
      components. These features indicate that feather stem cells are transcriptionally
      active cells for ribosomal and proteins synthesis. The cell surface of feather
      stem cells often shows small and irregular folds resembling microvilli in contact
      with the surrounding cells. The latter characteristics may be related to the
      exchange of molecules and/or with the migration of stem cells among other
      epithelial cells of the collar epithelium.

PMID- 25054195
TI  - President's page.  What a year!

PMID- 25054196
TI  - Chance identification of synchronous hairy cell leukemia and plasma cell myeloma
      in a potential HSC donor.

PMID- 25054197
TI  - Bodies of evidence? Lymphoglandular bodies in aspirate smears of bone marrow
      involved by aggressive large B-cell lymphoma.

PMID- 25054198
TI  - 6-hydroxy-3-succinoylpyridine hydroxylase catalyzes a central step of nicotine
      degradation in Agrobacterium tumefaciens S33.
AB  - Nicotine is a main alkaloid in tobacco and is also the primary toxic compound in
      tobacco wastes. It can be degraded by bacteria via either pyridine pathway or
      pyrrolidine pathway. Previously, a fused pathway of the pyridine pathway and the
      pyrrolidine pathway was proposed for nicotine degradation by Agrobacterium
      tumefaciens S33, in which 6-hydroxy-3-succinoylpyridine (HSP) is a key
      intermediate connecting the two pathways. We report here the purification and
      properties of an NADH-dependent HSP hydroxylase from A. tumefaciens S33. The 90
      kDa homodimeric flavoprotein catalyzed the oxidative decarboxylation of HSP to
      2,5-dihydroxypyridine (2,5-DHP) in the presence of NADH and FAD at pH 8.0 at a
      specific rate of about 18.8 +/- 1.85 umol min-1 mg protein-1. Its gene was
      identified by searching the N-terminal amino acid residues of the purified
      protein against the genome draft of the bacterium. It encodes a protein composed
      of 391 amino acids with 62% identity to HSP hydroxylase (HspB) from Pseudomonas
      putida S16, which degrades nicotine via the pyrrolidine pathway. Considering the
      application potential of 2,5-DHP in agriculture and medicine, we developed a
      route to transform HSP into 2,5-DHP with recombinant HSP hydroxylase and an NADH
      regenerating system (formate, NAD+ and formate dehydrogenase), via which around
      0.53 +/- 0.03 mM 2,5-DHP was produced from 0.76 +/- 0.01 mM HSP with a molar
      conversion as 69.7%. This study presents the biochemical properties of the key
      enzyme HSP hydroxylase which is involved in the fused nicotine degradation
      pathway of the pyridine and pyrrolidine pathways and a new green route to
      biochemically synthesize functionalized 2,5-DHP.

PMID- 25054199
TI  - Can occupancy-abundance models be used to monitor wolf abundance?
AB  - Estimating the abundance of wild carnivores is of foremost importance for
      conservation and management. However, given their elusive habits, direct
      observations of these animals are difficult to obtain, so abundance is more
      commonly estimated from sign surveys or radio-marked individuals. These methods
      can be costly and difficult, particularly in large areas with heavy forest cover.
      As an alternative, recent research has suggested that wolf abundance can be
      estimated from occupancy-abundance curves derived from "virtual" surveys of
      simulated wolf track networks. Although potentially more cost-effective, the
      utility of this approach hinges on its robustness to violations of its
      assumptions. We assessed the sensitivity of the occupancy-abundance approach to
      four assumptions: variation in wolf movement rates, changes in pack cohesion,
      presence of lone wolves, and size of survey units. Our simulations showed that
      occupancy rates and wolf pack abundances were biased high if track surveys were
      conducted when wolves made long compared to short movements, wolf packs were
      moving as multiple hunting units as opposed to a cohesive pack, and lone wolves
      were moving throughout the surveyed landscape. We also found that larger survey
      units (400 and 576 km2) were more robust to changes in these factors than smaller
      survey units (36 and 144 km2). However, occupancy rates derived from large survey
      units rapidly reached an asymptote at 100% occupancy, suggesting that these large
      units are inappropriate for areas with moderate to high wolf densities (>15
      wolves/1,000 km2). Virtually-derived occupancy-abundance relationships can be a
      useful method for monitoring wolves and other elusive wildlife if applied within
      certain constraints, in particular biological knowledge of the surveyed species
      needs to be incorporated into the design of the occupancy surveys. Further, we
      suggest that the applicability of this method could be extended by directly
      incorporating some of its assumptions into the modelling framework. 

PMID- 25054200
TI  - Mining TCGA data using Boolean implications.
AB  - Boolean implications (if-then rules) provide a conceptually simple, uniform and
      highly scalable way to find associations between pairs of random variables. In
      this paper, we propose to use Boolean implications to find relationships between
      variables of different data types (mutation, copy number alteration, DNA
      methylation and gene expression) from the glioblastoma (GBM) and ovarian serous
      cystadenoma (OV) data sets from The Cancer Genome Atlas (TCGA). We find hundreds
      of thousands of Boolean implications from these data sets. A direct comparison of
      the relationships found by Boolean implications and those found by commonly used
      methods for mining associations show that existing methods would miss
      relationships found by Boolean implications. Furthermore, many relationships
      exposed by Boolean implications reflect important aspects of cancer biology.
      Examples of our findings include cis relationships between copy number
      alteration, DNA methylation and expression of genes, a new hierarchy of mutations
      and recurrent copy number alterations, loss-of-heterozygosity of well-known tumor
      suppressors, and the hypermethylation phenotype associated with IDH1 mutations in
      GBM. The Boolean implication results used in the paper can be accessed at
      http://crookneck.stanford.edu/microarray/TCGANetworks/. 

PMID- 25054201
TI  - Progressively increased M50 responses to repeated sounds in autism spectrum
      disorder with auditory hypersensitivity: a magnetoencephalographic study.
AB  - The aim of this study was to investigate the differential time-course responses
      of the auditory cortex to repeated auditory stimuli in children with autism
      spectrum disorder (ASD) showing auditory hypersensitivity. Auditory-evoked field
      values were obtained from 21 boys with ASD (12 with and 9 without auditory
      hypersensitivity) and 15 age-matched typically developing controls. M50 dipole
      moments were significantly increased during the time-course study only in the ASD
      with auditory hypersensitivity compared with those for the other two groups. The
      boys having ASD with auditory hypersensitivity also showed more prolonged
      response duration than those in the other two groups. The response duration was
      significantly related to the severity of auditory hypersensitivity. We propose
      that auditory hypersensitivity is associated with decreased inhibitory
      processing, possibly resulting from an abnormal sensory gating system or
      dysfunction of inhibitory interneurons. 

PMID- 25054203
TI  - Temporal and contextual consistency of leadership in homing pigeon flocks.
AB  - Organized flight of homing pigeons (Columba livia) was previously shown to rely
      on simple leadership rules between flock mates, yet the stability of this social
      structuring over time and across different contexts remains unclear. We
      quantified the repeatability of leadership-based flock structures within a flight
      and across multiple flights conducted with the same animals. We compared two
      contexts of flock composition: flocks of birds of the same age and flight
      experience; and, flocks of birds of different ages and flight experience. All
      flocks displayed consistent leadership-based structures over time, showing that
      individuals have stable roles in the navigational decisions of the flock.
      However, flocks of balanced age and flight experience exhibited reduced
      leadership stability, indicating that these factors promote flock structuring.
      Our study empirically demonstrates that leadership and followership are
      consistent behaviours in homing pigeon flocks, but such consistency is affected
      by the heterogeneity of individual flight experiences and/or age. Similar
      evidence from other species suggests leadership as an important mechanism for
      coordinated motion in small groups of animals with strong social bonds. 

PMID- 25054204
TI  - Cleavage of Histone 3 by Cathepsin D in the involuting mammary gland.
AB  - The post-lactational regression of mammary gland is a complex multi-step process
      designed to conserve the biological function of the gland for next pregnancy.
      This developmental stage is a biological intrigue with great relevance to breast
      cancer research, and thus has been the subject of intensive scrutiny.
      Multipronged studies (microarray, proteomics profiling, animal knock-out models)
      have provided a repertoire of genes critical to involution. However, the caveat
      of these approaches remains in their failure to reveal post-translational
      modification(s), an emerging and critical aspect of gene regulation in
      developmental processes and mammary gland remodeling. The massive surge in the
      lysosomal enzymes concurrent with the onset of involution has been known for
      decades, and considered essential for "clearance" purposes. However, functional
      significance of these enzymes in diverse biological processes distinct from their
      proteolytic activity is just emerging. Studies from our laboratory had indicated
      specific post-translational modifications of the aspartyl endopeptidase Cathepsin
      D (CatD) at distinct stages mammary gland development. This study addresses the
      biological significance of these modifications in the involution process, and
      reveals that post-translational modifications drive CatD into the nucleus to
      cleave Histone 3. The cleavage of Histone 3 has been associated with cellular
      differentiation and could be critical instigator of involution process. From
      functional perspective, deregulated expression and increased secretion of CatD
      are associated with aggressive and metastatic phenotype of breast cancer. Thus
      unraveling CatD's physiological functions in mammary gland development will
      bridge the present gap in understanding its pro-tumorigenic/metastatic functions,
      and assist in the generation of tailored therapeutic approaches.

PMID- 25054206
TI  - Cytotoxicity and comparative binding mechanism of piperine with human serum
      albumin and alpha-1-acid glycoprotein.
AB  - Human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP) (acute phase
      protein) are the plasma proteins in blood system which transports many drugs. To
      understand the pharmacological importance of piperine molecule, here, we studied
      the anti-inflammatory activity of piperine on mouse macrophages (RAW 264.7) cell
      lines, which reveals that piperine caused an increase in inhibition growth of
      inflammated macrophages. Further, the fluorescence maximum quenching of proteins
      were observed upon binding of piperine to HSA and AGP through a static quenching
      mechanism. The binding constants obtained from fluorescence emission were found
      to be K(piperine) = 5.7 +/- .2 * 10(5) M(-1) and K(piperine) = 9.3+/- .25 * 10(4)
      M(-1) which correspond to the free energy of -7.8 and -6.71 kcal M(-1)at 25 
      degrees C for HSA and AGP, respectively. Further, circular dichrosim studies
      revealed that there is a marginal change in the secondary structural content of
      HSA due to partial destabilization of HSA-piperine complexes. Consequently,
      inference drawn from the site-specific markers (phenylbutazone, site I marker)
      studies to identify the binding site of HSA noticed that piperine binds at site I
      (IIA), which was further authenticated by molecular docking and molecular dynamic
      (MD) studies. The binding constants and free energy corresponding to experimental
      and computational analysis suggest that there are hydrophobic and hydrophilic
      interactions when piperine binds to HSA. Additionally, the MD studies have showed
      that HSA-piperine complex reaches equilibration state at around 3 ns, which prove
      that the HSA-piperine complex is stable in nature.

PMID- 25054205
TI  - HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women
      participating in a microbicide trial in Southern Africa are primarily directed
      toward gp120 and gp140 specificities.
AB  - BACKGROUND: Many participants in microbicide trials remain uninfected despite
      ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV
      specific immune responses in such women is important, since these responses may
      contribute to protection and could provide insight for the rational design of HIV
      1 vaccines. METHODS AND FINDINGS: We first conducted a pilot study to compare
      three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges)
      for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG
      antibodies from HIV-1-positive women reacted broadly across the full panel of
      eight HIV-1 envelope (Env) antigens tested, whereas IgA antibodies only reacted
      to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative
      women. The three sampling devices yielded equal HIV-1-specific antibody titers,
      as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs
      archived from 57 HIV seronegative women who participated in a microbicide
      efficacy trial in Southern Africa (HPTN 035). We detected vaginal IgA antibodies
      directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another
      three women, but did not detect Env-specific IgG antibodies in any women.
      CONCLUSION: Vaginal secretions of HIV-1 infected women contained IgG reactivity
      to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env
      binding antibodies in the vaginal secretions of HIV-1 uninfected women
      participating in the microbicide trial were restricted to the IgA subtype and
      were mostly directed at HIV-1 gp120/gp140.

PMID- 25054208
TI  - Modulating notochordal differentiation of human induced pluripotent stem cells
      using natural nucleus pulposus tissue matrix.
AB  - Human induced pluripotent stem cells (hiPSCs) can differentiate into notochordal
      cell (NC)-like cells when cultured in the presence of natural porcine nucleus
      pulposus (NP) tissue matrix. The method promises massive production of high
      quality, functional cells to treat degenerative intervertebral discs (IVDs).
      Based on our previous work, we further examined the effect of cell-NP matrix
      contact and culture medium on the differentiation, and further assessed the
      functional differentiation ability of the generated NC-like. The study showed
      that direct contact between hiPSCs and NP matrix can promote the differentiation
      yield, whilst both the contact and non-contact cultures can generate functional
      NC-like cells. The generated NC-like cells are highly homogenous regarding the
      expression of notochordal marker genes. A culture medium containing a cocktail of
      growth factors (FGF, EGF, VEGF and IGF-1) also supported the notochordal
      differentiation in the presence of NP matrix. The NC-like cells showed excellent
      functional differentiation ability to generate NP-like tissue which was rich in
      aggrecan and collagen type II; and particularly, the proteoglycan to collagen
      content ratio was as high as 12.5-17.5 which represents a phenotype close to NP
      rather than hyaline cartilage. Collectively, the present study confirmed the
      effectiveness and flexibility of using natural NP tissue matrix to direct
      notochordal differentiation of hiPSCs, and the potential of using the generated
      NC-like cells for treating IVD degeneration. 

PMID- 25054209
TI  - A proto-architecture for innate directionally selective visual maps.
AB  - Self-organizing artificial neural networks are a popular tool for studying visual
      system development, in particular the cortical feature maps present in real
      systems that represent properties such as ocular dominance (OD), orientation
      selectivity (OR) and direction selectivity (DS). They are also potentially useful
      in artificial systems, for example robotics, where the ability to extract and
      learn features from the environment in an unsupervised way is important. In this
      computational study we explore a DS map that is already latent in a simple
      artificial network. This latent selectivity arises purely from the cortical
      architecture without any explicit coding for DS and prior to any self-organising
      process facilitated by spontaneous activity or training. We find DS maps with
      local patchy regions that exhibit features similar to maps derived experimentally
      and from previous modeling studies. We explore the consequences of changes to the
      afferent and lateral connectivity to establish the key features of this proto
      architecture that support DS. 

PMID- 25054211
TI  - Designed synthesis of large-pore crystalline polyimide covalent organic
      frameworks.
AB  - Covalent organic frameworks (COFs) are an emerging class of porous crystalline
      polymers with a wide variety of applications. They are currently synthesized
      through only a few chemical reactions, limiting the access and exploitation of
      new structures and properties. Here we report that the imidization reaction can
      be used to prepare a series of polyimide (PI) COFs with pore size as large as 42
      * 53 A(2), which is among the largest reported to date, and surface area as high
      as 2,346 m(2) g(-1), which exceeds that of all amorphous porous PIs and is among
      the highest reported for two-dimensional COFs. These PI COFs are thermally stable
      up to 530  degrees C. We also assemble a large dye molecule into a COF that shows
      sensitive temperature-dependent luminescent properties. 

PMID- 25054212
TI  - Deep enteroscopy with standard endoscopes using a novel through-the-scope
      balloon.
AB  - BACKGROUND AND STUDY AIMS: A new on-demand enteroscopy (ODE) device has been
      designed to allow deep enteroscopy using a standard adult colonoscope with the
      aid of a novel through-the-scope balloon. The aims of the current study were to
      establish the feasibility, efficacy, and safety of ODE in performing anterograde
      and retrograde enteroscopy. PATIENTS AND METHODS: A retrospective, single-center
      study of 28 consecutive deep ODE procedures (11 anterograde and 17 retrograde)
      was performed. Diagnostic yield, therapeutic yield, technical success, procedure
      time, depth of maximal insertion (DMI), time to DMI, and adverse events were
      recorded. RESULTS: The mean diagnostic and therapeutic yields were 45 % and 36 %
      for anterograde enteroscopy and 59 % and 47 % for retrograde enteroscopy,
      respectively. Technical success was achieved in 100 %. For anterograde
      enteroscopy, the mean total procedure time was 24 minutes, with a mean DMI of 1.2
      m. For retrograde enteroscopy, the mean total procedure time was 31 minutes, with
      a mean DMI of 1.1 m. No adverse events were recorded. CONCLUSION: Deep
      enteroscopy using a novel through-the-scope balloon and standard endoscope
      appeared to be feasible and safe, with rapid procedures times.

PMID- 25054213
TI  - Peganumine A, a beta-carboline dimer with a new octacyclic scaffold from Peganum
      harmala.
AB  - Peganumine A (1), a new dimeric beta-carboline alkaloid characterized by a unique
      3,9-diazatetracyclo[6.5.2.0(1,9).0(3,8)]pentadec-2-one scaffold, was isolated
      from the seeds of Peganum harmala. The structure including the absolute
      configuration was determined by spectroscopic data, X-ray crystallography, ECD
      calculation, and CD exciton chirality approaches. Compound 1 showed moderate
      cytotoxic activity against MCF-7, PC-3, and HepG2 cells and selective effects on
      HL-60 cells with an IC50 value of 5.8 MUM. 

PMID- 25054214
TI  - Unusual presentation of visceral leishmaniasis in an HIV-infected patient.

PMID- 25054215
TI  - Anti-hyperglycaemic effect of Phragmenthera austroarabica A.G.Mill. & J.A.Nyberg
      extract in streptozotocin-induced diabetes in rats.
AB  - This study was undertaken to investigate the hypoglycaemic activity of
      Phragmenthera austroarabica A.G.Mill. & J.A.Nyberg extract and evaluate its
      possible antioxidant and anti-hyperlipidaemic effect in type 2 diabetic animal
      model. Type 2 diabetes was induced by a high-fat diet followed by injection with
      streptozotocin. Diabetic adult male Wistar rats were allocated into three groups
      and treated with pioglitazone HCl (PIO) or the extract of P. austroarabica
      A.G.Mill. & J.A.Nyberg (250 or 500 mg/kg b.wt.). In addition, a normal control
      group and a diabetic control group were used for comparison. Blood glucose,
      insulin resistance, oxidative stress parameter, antioxidant markers and serum
      lipids were evaluated. The extract of P. austroarabica A.G.Mill. & J.A.Nyberg
      exhibited a significant hypoglycaemia associated with antioxidant and anti
      hyperlipidaemic effects in diabetic rats. The antioxidant activities are
      responsible, at least partly, for the improvements that have been noticed in
      hyperglycaemia and insulin resistance of diabetic rats. The extract revealed no
      symptoms of toxicity. It is concluded that this plant might be considered as an
      excellent candidate for future study on diabetes mellitus. 

PMID- 25054216
TI  - Diazepam and fluoxetine decrease the stress response in zebrafish.
AB  - The presence of pharmaceutical products in the aquatic environment has been
      reported in several studies. However, the impact of these drugs on living
      organisms is still uncharacterized. Here, we investigated the effects of acute
      exposure to either diazepam or fluoxetine on the stress response in Danio rerio.
      We showed that diazepam and fluoxetine inhibited the stress axis in zebrafish.
      Intermediate concentrations of diazepam suppressed the stress response as
      measured by cortisol levels, whereas fluoxetine inhibited cortisol increase at
      concentrations similar to those found in the environment. These data suggest that
      the presence of psychoactive drugs in aquatic ecosystems could cause
      neuroendocrine dysfunction in fish. 

PMID- 25054217
TI  - Self-drying: a gecko's innate ability to remove water from wet toe pads.
AB  - When the adhesive toe pads of geckos become wet, they become ineffective in
      enabling geckos to stick to substrates. This result is puzzling given that many
      species of gecko are endemic to tropical environments where water covered
      surfaces are ubiquitous. We hypothesized that geckos can recover adhesive
      capabilities following exposure of their toe pads to water by walking on a dry
      surface, similar to the active self-cleaning of dirt particles. We measured the
      time it took to recover maximum shear adhesion after toe pads had become wet in
      two groups, those that were allowed to actively walk and those that were not.
      Keeping in mind the importance of substrate wettability to adhesion on wet
      surfaces, we also tested geckos on hydrophilic glass and an intermediately
      wetting substrate (polymethylmethacrylate; PMMA). We found that time to maximum
      shear adhesion recovery did not differ in the walking groups based on substrate
      wettability (22.7+/-5.1 min on glass and 15.4+/-0.3 min on PMMA) but did have a
      significant effect in the non-walking groups (54.3+/-3.9 min on glass and 27.8+/
      2.5 min on PMMA). Overall, we found that by actively walking, geckos were able to
      self-dry their wet toe pads and regain maximum shear adhesion significantly
      faster than those that did not walk. Our results highlight a unexpected property
      of the gecko adhesive system, the ability to actively self-dry and recover
      adhesive performance after being rendered dysfunctional by water. 

PMID- 25054221
TI  - Preventing postoperative pneumonia.

PMID- 25054218
TI  - White matter tract damage in the behavioral variant of frontotemporal and
      corticobasal dementia syndromes.
AB  - The phenotypes of the behavioral variant of frontotemporal dementia and the
      corticobasal syndrome present considerable clinical and anatomical overlap. The
      respective patterns of white matter damage in these syndromes have not been
      directly contrasted. Beyond cortical involvement, damage to white matter pathways
      may critically contribute to both common and specific symptoms in both
      conditions. Here we assessed patients with the behavioral variant of
      frontotemporal dementia and corticobasal syndrome with whole-brain diffusion
      tensor imaging to identify the white matter networks underlying these
      pathologies. Twenty patients with the behavioral variant of frontotemporal
      dementia, 19 with corticobasal syndrome, and 15 healthy controls were enrolled in
      the study. Differences in tract integrity between (i) patients and controls, and
      (ii) patients with the corticobasal syndrome and the behavioral variant of
      frontotemporal dementia were assessed with whole brain tract-based spatial
      statistics and analyses of regions of interest. Behavioral variant of
      frontotemporal dementia and the corticobasal syndrome shared a pattern of
      bilaterally decreased white matter integrity in the anterior commissure, genu and
      body of the corpus callosum, corona radiata and in the long intrahemispheric
      association pathways. Patients with the behavioral variant of frontotemporal
      dementia showed greater damage to the uncinate fasciculus, genu of corpus
      callosum and forceps minor. In contrast, corticobasal syndrome patients had
      greater damage to the midbody of the corpus callosum and perirolandic corona
      radiata. Whereas several compact white matter pathways were damaged in both the
      behavioral variant of frontotemporal dementia and corticobasal syndrome, the
      distribution and degree of white matter damage differed between them. These
      findings concur with the distinctive clinical manifestations of these conditions
      and may improve the in vivo neuroanatomical and diagnostic characterization of
      these disorders. 

PMID- 25054222
TI  - Field emission with ultralow turn on voltage from metal decorated carbon
      nanotubes.
AB  - A simple and scalable method of decorating 3D-carbon nanotube (CNT) forest with
      metal particles has been developed. The results observed in aluminum (Al)
      decorated CNTs and copper (Cu) decorated CNTs on silicon (Si) and Inconel are
      compared with undecorated samples. A significant improvement in the field
      emission characteristics of the cold cathode was observed with ultralow turn on
      voltage (Eto ~ 0.1 V/MUm) due to decoration of CNTs with metal nanoparticles.
      Contact resistance between the CNTs and the substrate has also been reduced to a
      large extent, allowing us to get stable emission for longer duration without any
      current degradation, thereby providing a possibility of their use in vacuum
      microelectronic devices. 

PMID- 25054223
TI  - Genes involved in the osteoarthritis process identified through genome wide
      expression analysis in articular cartilage; the RAAK study.
AB  - OBJECTIVE: Identify gene expression profiles associated with OA processes in
      articular cartilage and determine pathways changing during the disease process.
      METHODS: Genome wide gene expression was determined in paired samples of OA
      affected and preserved cartilage of the same joint using microarray analysis for
      33 patients of the RAAK study. Results were replicated in independent samples by
      RT-qPCR and immunohistochemistry. Profiles were analyzed with the online analysis
      tools DAVID and STRING to identify enrichment for specific pathways and protein
      protein interactions. RESULTS: Among the 1717 genes that were significantly
      differently expressed between OA affected and preserved cartilage we found
      significant enrichment for genes involved in skeletal development (e.g. TNFRSF11B
      and FRZB). Also several inflammatory genes such as CD55, PTGES and TNFAIP6,
      previously identified in within-joint analyses as well as in analyses comparing
      preserved cartilage from OA affected joints versus healthy cartilage were among
      the top genes. Of note was the high up-regulation of NGF in OA cartilage. RT-qPCR
      confirmed differential expression for 18 out of 19 genes with expression changes
      of 2-fold or higher, and immunohistochemistry of selected genes showed a
      concordant change in protein expression. Most of these changes associated with OA
      severity (Mankin score) but were independent of joint-site or sex. CONCLUSION: We
      provide further insights into the ongoing OA pathophysiological processes in
      cartilage, in particular into differences in macroscopically intact cartilage
      compared to OA affected cartilage, which seem relatively consistent and
      independent of sex or joint. We advocate that development of treatment could
      benefit by focusing on these similarities in gene expression changes and/or
      pathways.

PMID- 25054225
TI  - Defining and dividing the greater Caribbean: insights from the biogeography of
      shorefishes.
AB  - The Greater Caribbean biogeographic region is the high-diversity heart of the
      Tropical West Atlantic, one of four global centers of tropical marine
      biodiversity. The traditional view of the Greater Caribbean is that it is limited
      to the Caribbean, West Indies, southwest Gulf of Mexico and tip of Florida, and
      that, due to its faunal homogeneity, lacks major provincial subdivisions. In this
      scenario the northern 2/3 of the Gulf of Mexico and southeastern USA represent a
      separate temperate, "Carolinian" biogeographic region. We completed a
      comprehensive re-assessment of the biogeography of the Greater Caribbean by
      comparing the distributions of 1,559 shorefish species within 45 sections of
      shelf waters of the Greater Caribbean and adjacent areas. This analysis shows
      that that the Greater Caribbean occupies a much larger area than usually thought,
      extending south to at least Guyana, and north to encompass the entire Carolinian
      area. Rather than being homogenous, the Greater Caribbean is divided into three
      major provinces, each with a distinctive, primarily tropical fauna: (1) a
      central, tropical province comprising the West Indies, Bermuda and Central
      America; (2) a southern, upwelling-affected province spanning the entire
      continental shelf of northern South America; and (iii) a northern, subtropical
      province that includes all of the Gulf of Mexico, Florida and southeastern USA.
      This three-province pattern holds for both reef- and soft bottom fishes,
      indicating a general response by demersal fishes to major variation in provincial
      shelf environments. Such environmental differences include latitudinal variation
      in sea temperature, availability of major habitats (coral reefs, soft bottom
      shorelines, and mangroves), and nutrient additions from upwelling areas and large
      rivers. The three-province arrangement of the Greater Caribbean broadly resembles
      and has a similar environmental basis to the provincial arrangement of its sister
      biogeographic region, the Tropical Eastern Pacific. 

PMID- 25054224
TI  - Single administration of p2TA (AB103), a CD28 antagonist peptide, prevents
      inflammatory and thrombotic reactions and protects against gastrointestinal
      injury in total-body irradiated mice.
AB  - The goal of this study was to elucidate the action of the CD28 mimetic peptide
      p2TA (AB103) that attenuates an excessive inflammatory response in mitigating
      radiation-induced inflammatory injuries. BALB/c and A/J mice were divided into
      four groups: Control (C), Peptide (P; 5 mg/kg of p2TA peptide), Radiation (R;
      total body irradiation with 8 Gy gamma-rays), and Radiation + Peptide (RP;
      irradiation followed by p2TA peptide 24 h later). Gastrointestinal tissue damage
      was evaluated by analysis of jejunum histopathology and immunohistochemistry for
      cell proliferation (Cyclin D1) and inflammation (COX-2) markers, as well as the
      presence of macrophages (F4/80). Pro-inflammatory cytokines IL-6 and KC as well
      as fibrinogen were quantified in plasma samples obtained from the same mice. Our
      results demonstrated that administration of p2TA peptide significantly reduced
      the irradiation-induced increase of IL-6 and fibrinogen in plasma 7 days after
      exposure. Seven days after total body irradiation with 8 Gy of gamma rays numbers
      of intestinal crypt cells were reduced and villi were shorter in irradiated
      animals compared to the controls. The p2TA peptide delivery 24 h after
      irradiation led to improved morphology of villi and crypts, increased Cyclin D1
      expression, decreased COX-2 staining and decreased numbers of macrophages in
      small intestine of irradiated mice. Our study suggests that attenuation of CD28
      signaling is a promising therapeutic approach for mitigation of radiation-induced
      tissue injury. 

PMID- 25054226
TI  - 2-Butanol and butanone production in Saccharomyces cerevisiae through combination
      of a B12 dependent dehydratase and a secondary alcohol dehydrogenase using a TEV
      based expression system.
AB  - 2-Butanol and its chemical precursor butanone (methyl ethyl ketone--MEK) are
      chemicals with potential uses as biofuels and biocommodity chemicals. In order to
      produce 2-butanol, we have demonstrated the utility of using a TEV-protease based
      expression system to achieve equimolar expression of the individual subunits of
      the two protein complexes involved in the B12-dependent dehydratase step (from
      the pdu-operon of Lactobacillus reuteri), which catalyze the conversion of meso
      2,3-butanediol to butanone. We have furthermore identified a NADH dependent
      secondary alcohol dehydrogenase (Sadh from Gordonia sp.) able to catalyze the
      subsequent conversion of butanone to 2-butanol. A final concentration of 4+/-0.2
      mg/L 2-butanol and 2+/-0.1 mg/L of butanone was found. A key factor for the
      production of 2-butanol was the availability of NADH, which was achieved by
      growing cells lacking the GPD1 and GPD2 isogenes under anaerobic conditions.

PMID- 25054227
TI  - Characterization of the bacterial communities of life stages of free living lone
      star ticks (Amblyomma americanum).
AB  - The lone star tick (Amblyomma americanum) is an abundant and aggressive biter of
      humans, domestic animals, and wildlife in the southeastern-central USA and an
      important vector of several known and suspected zoonotic bacterial pathogens.
      However, the biological drivers of bacterial community variation in this tick are
      still poorly defined. Knowing the community context in which tick-borne bacterial
      pathogens exist and evolve is required to fully understand the ecology and
      immunobiology of the ticks and to design effective public health and veterinary
      interventions. We performed a metagenomic survey of the bacterial communities of
      questing A. americanum and tested 131 individuals (66 nymphs, 24 males, and 41
      females) from five sites in three states. Pyrosequencing was performed with
      barcoded eubacterial primers targeting variable 16S rRNA gene regions 5-3. The
      bacterial communities were dominated by Rickettsia (likely R. amblyommii) and an
      obligate Coxiella symbiont, together accounting for 6.7-100% of sequences per
      tick. DNAs from Midichloria, Borrelia, Wolbachia, Ehrlichia, Pseudomonas, or
      unidentified Bacillales, Enterobacteriaceae, or Rhizobiales groups were also
      detected frequently. Wolbachia and Midichloria significantly co-occurred in
      Georgia (p<0.00001), but not in other states. The significance of the Midichloria
      Wolbachia co-occurrence is unknown. Among ticks collected in Georgia, nymphs
      differed from adults in both the composition (p = 0.002) and structure (p =
      0.002) of their bacterial communities. Adults differed only in their community
      structure (p = 0.002) with males containing more Rickettsia and females
      containing more Coxiella. Comparisons among adult ticks collected in New York and
      North Carolina supported the findings from the Georgia collection despite
      differences in geography, collection date, and sample handling, implying that the
      differences detected are consistent attributes. The data also suggest that some
      members of the bacterial community change during the tick life cycle and that
      some sex-specific attributes may be detectable in nymphs. 

PMID- 25054228
TI  - Aberrant expression of interleukin-1beta and inflammasome activation in human
      malignant gliomas.
AB  - OBJECTIVE: Glioblastoma is the most frequent and malignant form of primary brain
      tumor with grave prognosis. Mounting evidence supports that chronic inflammation
      (such as chronic overactivation of IL-1 system) is a crucial event in
      carcinogenesis and tumor progression. IL-1 also is an important cytokine with
      species-dependent regulations and roles in CNS cell activation. While much
      attention is paid to specific anti-tumor immunity, little is known about the role
      of chronic inflammation/innate immunity in glioma pathogenesis. In this study, we
      examined whether human astrocytic cells (including malignant gliomas) can produce
      IL-1 and its role in glioma progression. METHODS: We used a combination of cell
      culture, real-time PCR, ELISA, western blot, immunocytochemistry, siRNA and
      plasmid transfection, micro-RNA analysis, angiogenesis (tube formation) assay,
      and neurotoxicity assay. RESULTS: Glioblastoma cells produced large quantities of
      IL-1 when activated, resembling macrophages/microglia. The activation signal was
      provided by IL-1 but not the pathogenic components LPS or poly IC. Glioblastoma
      cells were highly sensitive to IL-1 stimulation, suggesting its relevance in
      vivo. In human astrocytes, IL-1beta mRNA was not translated to protein. Plasmid
      transfection also failed to produce IL-1 protein, suggesting active repression.
      Suppression of microRNAs that can target IL-1alpha/beta did not induce IL-1
      protein. Glioblastoma IL-1beta processing occurred by the NLRP3 inflammasome, and
      ATP and nigericin increased IL-1beta processing by upregulating NLRP3 expression,
      similar to macrophages. RNAi of annexin A2, a protein strongly implicated in
      glioma progression, prevented IL-1 induction, demonstrating its new role in
      innate immune activation. IL-1 also activated Stat3, a transcription factor
      crucial in glioma progression. IL-1 activated glioblastoma-conditioned media
      enhanced angiogenesis and neurotoxicity. CONCLUSIONS: Our results demonstrate
      unique, species-dependent immune activation mechanisms involving human astrocytes
      and astrogliomas. Specifically, the ability to produce IL-1 by glioblastoma cells
      may confer them a mesenchymal phenotype including increased migratory capacity,
      unique gene signature and proinflammatory signaling.

PMID- 25054229
TI  - Inhibitory action of benzo[alpha]pyrene on hepatic lipoprotein receptors in vitro
      and on liver lipid homeostasis in mice.
AB  - BACKGROUND: Dyslipidemia associated with obesity often manifests as increased
      plasma LDL and triglyceride-rich lipoprotein levels suggesting changes in hepatic
      lipoprotein receptor status. Persistent organic pollutants have been recently
      postulated to contribute to the obesity etiology by increasing adipogenesis, but
      little information is available on their potential effect on hepatic lipoprotein
      metabolism. OBJECTIVE: The objective of this study was to investigate the effect
      of the common environmental pollutant, benzo[alpha]pyrene (B[alpha]P) on two
      lipoprotein receptors, the LDL-receptor and the lipolysis-stimulated lipoprotein
      receptor (LSR) as well as the ATP-binding cassette transporter A1 (ABCA1) using
      cell and animal models. RESULTS: LSR, LDL-receptor as well as ABCA1 protein
      levels were significantly decreased by 26-48% in Hepa1-6 cells incubated (<2 h)
      in the presence of B[alpha]P (<=1 uM). Real-time PCR analysis and lactacystin
      studies revealed that this effect was due primarily to increased proteasome, and
      not lysosomal-mediated degradation rather than decreased transcription.
      Furthermore, ligand blots revealed that lipoproteins exposed to 1 or 5 uM
      B[alpha]P displayed markedly decreased (42-86%) binding to LSR or LDL-receptor.
      B[alpha]P-treated (0.5 mg/kg/48 h, i.p. 15 days) C57BL/6J mice displayed higher
      weight gain, associated with significant increases in plasma cholesterol,
      triglycerides, and liver cholesterol content, and decreased hepatic LDL-receptor
      and ABCA1 levels. Furthermore, correlational analysis revealed that B[alpha]P
      abolished the positive association observed in control mice between the LSR and
      LDL-receptor. Interestingly, levels of other proteins involved in liver
      cholesterol metabolism, ATP-binding cassette transporter G1 and scavenger
      receptor-BI, were decreased, while those of acyl-CoA:cholesterol acyltransferase
      1 and 2 were increased in B[alpha]P-treated mice. CONCLUSIONS: B[alpha]P
      demonstrates inhibitory action on LSR and LDL-R, as well as ABCA1, which we
      propose leads to modified lipid status in B[alpha]P-treated mice, thus providing
      new insight into mechanisms underlying the involvement of pollutants in the
      disruption of lipid homeostasis, potentially contributing to dyslipidemia
      associated with obesity.

PMID- 25054230
TI  - Cystic fibrosis and AA amyloidosis: a survey in the French cystic fibrosis
      network.
AB  - INTRODUCTION: To define the characteristics of CF patients developing AA
      amyloidosis. METHODS: A 30-year retrospective survey conducted within the
      national French CF network to identify cases of CF associated with AA
      amyloidosis. RESULTS: Nine cases of AA amyloidosis were identified (CF prevalence
      in France is approximately 6000 patients) and sufficient data were collected in
      six. The clinical presentation was renal disease in four cases, a compressive
      goiter in one case, and epigastric pain in one case. Organ involvement included
      kidney disease in all cases (proteinuria, with a median age at onset of 24 years,
      4 cases with nephrotic syndrome, 5 with renal failure); gastrointestinal (4 cases
      with duodenal ulcer); thyroid (2 cases); and hepatobiliary system (3 cases). The
      median age at diagnosis of CF was 6.5 years. Five patients had pancreatic
      insufficiency. All patients had chronic respiratory infections requiring
      intravenous antibiotics several times a year. Five patients have died, at a
      median age of 29 years and a median duration of 6 years after the onset of
      proteinuria. CONCLUSION: AA amyloidosis is a rare but morbid complication of CF.
      Renal involvement is predominant.

PMID- 25054231
TI  - Enhancement of arsenic trioxide-mediated changes in human induced pluripotent
      stem cells (IPS).
AB  - Induced pluripotent stem cells (IPS) are an artificially derived type of
      pluripotent stem cell, showing many of the same characteristics as natural
      pluripotent stem cells. IPS are a hopeful therapeutic model; however there is a
      critical need to determine their response to environmental toxins. Effects of
      arsenic on cells have been studied extensively; however, its effect on IPS is yet
      to be elucidated. Arsenic trioxide (ATO) has been shown to inhibit cell
      proliferation, induce apoptosis and genotoxicity in many cells. Based on ATOs
      action in other cells, we hypothesize that it will induce alterations in
      morphology, inhibit cell viability and induce a genotoxic effect on IPS. Cells
      were treated for 24 hours with ATO (0-9 ug/mL). Cell morphology, viability and
      DNA damage were documented. Results indicated sufficient changes in morphology of
      cell colonies mainly in cell ability to maintain grouping and ability to remain
      adherent. Cell viability decreased in a dose dependent manner. There were
      significant increases in tail length and moment as well as destruction of intact
      DNA as concentration increased. Exposure to ATO resulted in a reproducible dose
      dependent sequence of events marked by changes in morphology, decrease of cell
      viability, and induction of genotoxicity in IPS. 

PMID- 25054233
TI  - A perturbative renormalization group approach to driven quantum systems.
AB  - We use a perturbative momentum shell renormalization group (RG) approach to study
      the properties of a driven quantum system at zero temperature. To illustrate the
      technique, we consider a bosonic phi(4) theory with an arbitrary time dependent
      interaction parameter lambda(t) = lambda f(omega0t), where omega0 is the drive
      frequency and we derive the RG equations for the system using a Keldysh
      diagrammatic technique. We show that the scaling of omega0 is analogous to that
      of temperature for a system in thermal equilibrium and its presence provides a
      cutoff scale for the RG flow. We analyze the resultant RG equations, derive an
      analytical condition for such a drive to take the system out of the gaussian
      regime, and show that the onset of the non-gaussian regime occurs concomitantly
      with the appearance of non-perturbative mode coupling terms in the effective
      action of the system. We supplement the above-mentioned results by obtaining them
      from equations of motion of the bosons and discuss their significance for systems
      near critical points described by time-dependent Landau-Ginzburg theories.

PMID- 25054234
TI  - Competitive assembly to increase the performance of the DNA/carbon-nanomaterial
      based sensing platform.
AB  - Increasing the rate of target binding on the surface and enhancing the
      fluorescence signal restoration efficiency are critical to the desirable
      biomedical application of carbon nanomaterials, for example, single-walled carbon
      nanotubes (SWNTs). We describe here a strategy to increase the target binding
      rate and enhance the fluorescence signal restoration efficiency on the DNA
      functionalized SWNT surface using a short complementary DNA (scDNA) strand. The
      scDNA causes up to a 2.5-fold increase in association rate and 4-fold increase in
      fluorescence signal restoration by its competitive assembly on the
      nanostructure's surface and inducing a conformational change that extends the DNA
      away from the surface, making it more available to bind target nucleic acids. The
      scDNA-induced enhancement of binding kinetics and fluorescence signal restoration
      efficiency is a general phenomenon that occurred with all sequences and surfaces
      investigated. Through this competitive assembly strategy of scDNA, performance
      improvement of the carbon-nanomaterial-based biosensing platform for both in
      vitro detection and live cell imaging can be reached. 

PMID- 25054235
TI  - Azulene methacrylate polymers: synthesis, electronic properties, and solar cell
      fabrication.
AB  - We report the synthesis of novel azulene-substituted methacrylate polymers by
      free radical polymerization, in which the azulene moieties represent hydrophobic
      dipoles strung pendant to the polymer backbone and impart unique electronic
      properties to the polymers. Tunable optoelectronic properties were realized by
      adjusting the azulene density, ranging from homopolymers (having one azulene
      group per repeat unit) to copolymers in which the azulene density was diluted
      with other pendant groups. Treating these polymers with organic acids revealed
      optical and excitonic behavior that depended critically on the azulene density
      along the polymer chain. Copolymers of azulene with zwitterionic methacrylates
      proved useful as cathode modification layers in bulk-heterojunction solar cells,
      where the relative azulene content affected the device metrics and the power
      conversion efficiency reached 7.9%. 

PMID- 25054232
TI  - Bisphenol-A: epigenetic reprogramming and effects on reproduction and behavior.
AB  - Bisphenol A (BPA) is a synthetic compound used in the production of many
      polycarbonate plastics and epoxy resins. It is one of the most widely produced
      chemicals in the world today and is found in most canned goods, plastics, and
      even household dust. Exposure to BPA is almost universal: most people have
      measurable amounts of BPA in both urine and serum. BPA is similar in structure to
      estradiol and can bind to multiple targets both inside and outside the nucleus,
      in effect acting as an endocrine disruptor. Research on BPA exposure has
      accelerated in the past decade with findings suggesting that perinatal exposure
      to BPA can negatively impact both male and female reproduction, create
      alterations in behavior, and act as a carcinogen. BPA can have both short term
      and long term effects with the latter typically occurring through epigenetic
      mechanisms such as DNA methylation. This review will draw on both human and
      animal studies in an attempt to synthesize the literature and examine the effects
      of BPA exposure on reproduction, behavior, and carcinogenesis with a focus on the
      potential epigenetic mechanisms by which it acts. 

PMID- 25054236
TI  - Probing the site-dependent Kondo response of nanostructured graphene with organic
      molecules.
AB  - TCNQ molecules are used as a sensitive probe for the Kondo response of the
      electron gas of a nanostructured graphene grown on Ru(0001) presenting a moire
      pattern. All adsorbed molecules acquired an extra electron by charge transfer
      from the substrate, but only those adsorbed in the FCC-Top areas of the moire
      show magnetic moment and Kondo resonance in the STS spectra. DFT calculations
      trace back this behavior to the existence of a surface resonance in the low areas
      of the graphene moire, whose density distribution strongly depends on the
      stacking sequence of the moire area and effectively quenches the magnetic moment
      for HCP-Top sites. 

PMID- 25054238
TI  - Cooperation for a competitive position: The impact of hospital cooperation
      behavior on organizational performance.
AB  - BACKGROUND: Several public policy initiatives, particularly those involving
      managed care, aim to enhance cooperation between partners in the health care
      sector because it is expected that such cooperation will reduce costs and
      generate additional revenue. However, empirical evidence regarding the effects of
      cooperation on hospital performance is scarce, particularly with respect to
      creating a comprehensive measure of cooperation behavior. PURPOSE: The aim of
      this study is to investigate the impact of hospital cooperation behavior on
      organizational performance. We differentiate between horizontal and vertical
      cooperation using two alternative measures-cooperation depth and cooperation
      breadth-and include the interaction effects between both cooperation directions.
      METHODOLOGY: Data are derived from a survey of German hospitals and combined with
      objective performance information from annual financial statements. Generalized
      linear regression models are used. FINDINGS: The study findings provide insight
      into the nature of hospitals' cooperation behavior. In particular, we show that
      there are negative synergies between horizontal administrative cooperation
      behavior and vertical cooperation behavior. Whereas the depth and breadth of
      horizontal administrative cooperation positively affect financial performance
      (when there is no vertical cooperation), vertical cooperation positively affects
      financial performance (when there is no horizontal administrative cooperation)
      only when cooperation is broad (rather than deep). PRACTICAL IMPLICATIONS:
      Horizontal cooperation is generally more effective than vertical cooperation at
      improving financial performance. Hospital managers should consider the negative
      interaction effect when making decisions about whether to recommend a cooperative
      relationship in a horizontal or vertical direction. In addition, managers should
      be aware of the limited financial benefit of cooperation behavior.

PMID- 25054237
TI  - Synthesis, crystal structure and biological activity of 2-hydroxyethylammonium
      salt of p-aminobenzoic acid.
AB  - p-Aminobenzoic acid (pABA) plays important roles in a wide variety of metabolic
      processes. Herein we report the synthesis, theoretical calculations,
      crystallographic investigation, and in vitro determination of the biological
      activity and phytotoxicity of the pABA salt, 2-hydroxyethylammonium p
      aminobenzoate (HEA-pABA). The ability of neutral and anionic forms of pABA to
      interact with TIR1 pocket was investigated by calculation of molecular
      electrostatic potential maps on the accessible surface area, docking experiments,
      Molecular Dynamics and Quantum Mechanics/Molecular Mechanics calculations. The
      docking study of the folate precursor pABA, its anionic form and natural auxin
      (indole-3-acetic acid, IAA) with the auxin receptor TIR1 revealed a similar
      binding mode in the active site. The phytotoxic evaluation of HEA-pABA, pABA and
      2-hydroxyethylamine (HEA) was performed on the model plant Arabidopsis thaliana
      ecotype Col 0 at five different concentrations. HEA-pABA and pABA acted as
      potential auxin-like regulators of root development in Arabidopsis thaliana (0.1
      and 0.2 mM) and displayed an agravitropic root response at high concentration (2
      mM). This study suggests that HEA-pABA and pABA might be considered as potential
      new regulators of plant growth. 

PMID- 25054239
TI  - Conserved residues of the human mitochondrial holocytochrome c synthase mediate
      interactions with heme.
AB  - C-type cytochromes are distinguished by the covalent attachment of a heme
      cofactor, a modification that is typically required for its subsequent folding,
      stability, and function. Heme attachment takes place in the mitochondrial
      intermembrane space and, in most eukaryotes, is mediated by holocytochrome c
      synthase (HCCS). HCCS is the primary component of the eukaryotic cytochrome c
      biogenesis pathway, known as System III. The catalytic function of HCCS depends
      on its ability to coordinate interactions between its substrates: heme and
      cytochrome c. Recent advancements in the recombinant expression and purification
      of HCCS have facilitated comprehensive analyses of the roles of conserved
      residues in HCCS, as demonstrated in this study. Previously, we proposed a four
      step model describing HCCS-mediated cytochrome c assembly, identifying a
      conserved histidine residue (His154) as an axial ligand to the heme iron. In this
      study, we performed a systematic mutational analysis of 17 conserved residues in
      HCCS, and we provide evidence that the enzyme contains two heme-binding domains.
      Our data indicate that heme contacts mediated by residues within these domains
      modulate the dynamics of heme binding and contribute to the stability of the HCCS
      heme-cytochrome c steady state ternary complex. While some residues are essential
      for initial heme binding (step 1), others impact the subsequent release of the
      holocytochrome c product (step 4). Certain HCCS mutants that were defective in
      heme binding were corrected for function by exogenous aminolevulinic acid (ALA,
      the precursor to heme). This chemical "correction" supports the proposed role of
      heme binding for the corresponding residues. 

PMID- 25054240
TI  - Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.
AB  - WNT signaling mediates various physiological and pathological processes. We
      previously showed that WNT10A is a novel angio/stromagenic factor involved in
      such processes as tumor growth, wound healing and tissue fibrosis. In this study,
      we investigated the role of WNT10A in promoting the fibrosis that is central to
      the pathology of acute interstitial nephritis (AIN). We initially asked whether
      there is an association between kidney function (estimated glomerular filtration
      rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with
      AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR
      than WNT10A-negative patients. However, changes in kidney function were not
      related to the level of expression of other WNT family members. Furthermore,
      there was positive correlation between WNT10A and alpha-SMA expression. We next
      investigated the involvement of WNT10A in kidney fibrosis processes using COS1
      cells, a kidney fibroblast cell line. WNT10A overexpression increased the level
      of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A
      overexpression renders cells resistant to apoptosis induced by hydrogen peroxide
      and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate
      with kidney dysfunction in AIN.

PMID- 25054243
TI  - Robotic, intraperitoneal harvest of the rectus abdominis muscle.
AB  - BACKGROUND: The rectus abdominis muscle is a workhorse for free and pedicled
      muscle coverage. Traditional harvest violates the anterior rectus sheath and
      requires an abdominal incision. Robotic harvest can be reliably and efficiently
      performed using three ports and no additional incisions. METHODS: Ten robotic
      rectus muscle harvests were performed at three institutions as free flaps for
      extremity coverage and pedicled flaps for minimally invasive pelvic surgery
      requiring soft-tissue reconstruction. Three contralateral ports and an
      intraperitoneal approach were used in each harvest. Demographic information,
      operative variables, and outcomes were recorded. RESULTS: All cases were
      completed robotically by three surgeons at three different institutions. Four
      muscles were harvested as free flaps for lower extremity and six muscles were
      used as pedicled flaps, three for abdominopelvic defect reconstruction and two
      for protection of visceral repair following salvage prostatectomy or anterior
      pelvic exenteration. Average robotic setup time was 15 minutes. Average robotic
      harvest time was 45 minutes. Two 8-mm ports and one 12-mm port were used in each
      case. One patient developed a grade I decubitus ulcer during an extended
      operation. There were no other complications. All muscles were completely viable
      following harvest. There were no conversions to open technique, and no hernias or
      bulges were noted. CONCLUSIONS: Robotic rectus muscle harvest is safe, efficient,
      and reproducible. The anterior rectus sheath can be left completely intact,
      eliminating incisional morbidity. The cumulative incisional length can be less
      than 2 inches even for extensive, multiservice pelvic procedures. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 25054242
TI  - Perceptions of the risks and benefits of upper limb transplantation among
      individuals with upper limb amputations.
AB  - BACKGROUND: Upper limb transplantation is a life-enhancing rather than life
      saving procedure. Little research has investigated how individuals with upper
      limb amputations perceive the benefits and risks of this complex procedure. To
      address this knowledge gap, the authors conducted qualitative research with
      individuals with upper limb amputations to understand their perspectives.
      METHODS: Twenty-two individuals with upper limb amputations (age range, 24 to 73
      years) participated in a focus group (n=5) or semistructured interview (n=17)
      about the benefits and risks of upper limb transplantation. Data were analyzed by
      means of constant comparative methods and a two-phase analysis process. RESULTS:
      Participants identified enhanced functional performance and improved appearance
      as the greatest potential benefits. Over half of participants indicated that
      function was a more important consideration than appearance. Enhanced function
      performance was a relative concept strongly influenced by individual
      expectations, which varied widely. Increased sensation, psychological well-being,
      and social acceptability were also described as potential benefits. Identified
      risks included health risks and the demands of transplantation and recovery,
      decreased functional performance, and uncertainty over outcomes from upper limb
      transplantation as an experimental procedure. Participants also expressed
      concerns regarding the psychological impact of negative outcomes and adverse
      events. CONCLUSIONS: Participants had a large variation in their perceived
      importance of the many risks and benefits of upper limb transplantation. These
      findings elucidate how potential upper limb transplantation candidates evaluate
      the benefits and risks of the procedure. The findings can also inform important
      issues to address and outcomes to assess in the pretransplant and posttransplant
      settings.

PMID- 25054244
TI  - Normobaric hyperoxygenation enhances initial survival, regeneration, and final
      retention in fat grafting.
AB  - BACKGROUND: Fat grafting is a promising modality for soft-tissue
      augmentation/reconstruction. However, grafted fat tissue is not initially
      perfused and relies on plasmatic diffusion from the recipient bed until
      revascularization occurs. The authors evaluated the therapeutic effects of
      normobaric hyperoxygenation for enhancing fat graft retention. METHODS: Aspirated
      human fat tissue was cultured under tissue hypoxia (1% oxygen), normoxia (6%),
      and hyperoxia (20%) levels, and evaluated for adipocyte viability. Inguinal fat
      pads were autografted under mouse scalps (n=36), and mice were housed in either
      20% (control) or 60% (normobaric hyperoxygenation) atmospheric oxygen for the
      first 3 days, and then returned to normoxia. Samples harvested at 0, 1, 2, 4, 8,
      and 12 weeks were analyzed immunohistochemically for adipocyte viability and
      regeneration. RESULTS: Organ culture adipocytes died more quickly under lower
      oxygen tensions; thus, hyperoxygenation of recipient tissues may delay adipocyte
      death after fat grafting. Autografted mouse adipose tissue underwent dynamic
      remodeling, from ischemic degeneration to partial regeneration, over 12 weeks.
      Normobaric hyperoxygenation grafted samples showed significantly larger survival
      zones and engraftment scores (calculated using sample weight and adipocyte
      viability) at 1 and 12 weeks, respectively, than control samples. In addition,
      adipocyte regeneration (number of perilipin-positive preadipocytes), which peaked
      at 4 weeks, was significantly increased in normobaric hyperoxygenation samples.
      CONCLUSION: The normobaric hyperoxygenation protocol using 60% oxygen can be
      safely applied to enhance adipocyte survival, regeneration, and final engraftment
      after fat grafting.

PMID- 25054245
TI  - Lessons learned from the American College of Surgeons National Surgical Quality
      Improvement Program Database: has centralized data collection improved immediate
      breast reconstruction outcomes and safety?
AB  - BACKGROUND: The American College of Surgeons National Surgical Quality
      Improvement Program database was implemented to longitudinally track surgical 30
      day surgical outcomes and complications. The authors analyze the program-reported
      outcomes for immediate breast reconstruction from 2007 to 2011, to assess whether
      longitudinal data collection has improved national outcomes and to highlight
      areas in need of continued improvement. METHODS: The authors reviewed the
      database from 2007 to 2011 and identified encounters for immediate breast
      reconstruction using Current Procedural Terminology codes for prosthetic and
      autologous reconstruction. Demographics and comorbidities were tabulated for all
      patients. Postoperative complications analyzed included surgical-site infection,
      wound dehiscence, implant or flap loss, pulmonary embolism, and respiratory
      infections. RESULTS: A total of 15,978 patients underwent mastectomy and
      immediate reconstruction. Fewer smokers underwent immediate reconstruction over
      time (p=0.126), whereas more obese patients (p=0.001) and American Society of
      Anesthesiologists class 3 and 4 patients (p<0.001) underwent surgery. An overall
      increase in superficial surgical-site infection was noted, from 1.7 percent to
      2.3 percent (p=0.214). Wound dehiscence (p=0.036) increased over time, whereas
      implant loss (p=0.015) and flap loss (p=0.012) decreased over time. Mean
      operative times increased over the analyzed years, as did all complications for
      prosthetic and autologous reconstruction. CONCLUSIONS: The American College of
      Surgeons National Surgical Quality Improvement Program data set has shown an
      increase in complications for immediate breast reconstruction over time, because
      of a longitudinally higher number of comorbid patients and longer operative
      times. This knowledge allows plastic surgeons the unique opportunity to improve
      patient selection criteria and efficiency. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 25054246
TI  - Outcome of osseointegrated dental implants in double-barrel and vertically
      distracted fibula osteoseptocutaneous free flaps for segmental mandibular defect
      reconstruction.
AB  - BACKGROUND: Osseointegrated dental implants in double-barrel, or single-barrel
      and then vertically distracted, fibula osteoseptocutaneous free flaps can achieve
      segmental mandibular reconstruction, dental rehabilitation, and premorbid facial
      height. However, it remains unknown which configuration provides better
      osseointegration outcomes. METHODS: Between 2003 and 2009, all patients who
      underwent segmental mandibular defect reconstruction using vertical distraction
      osteogenesis of single-barrel fibula with secondary osseointegration (group A, 10
      patients and 35 osseointegrated dental implants) or double-barrel fibula with
      primary osseointegration (group B, 13 patients and 36 osseointegrated dental
      implants) were evaluated prospectively for crown-implant ratios, mesial/distal
      marginal bone losses, and complications. In group B, 18 osseointegrated dental
      implants were surrounded by palatal mucosal grafts; the other retained fibula
      skin paddles. RESULTS: Palatal mucosal grafts in group B improved mesial
      (p<0.001) and distal (p<0.001) marginal bone losses. Mesial marginal bone loss of
      group B with palatal mucosal grafts was better than that of group A (p<0.05),
      despite higher crown-implant ratios in group A (p<0.01). Mesial (p<0.01) and
      distal (p<0.05) marginal bone losses of group A were better than that of group B
      osseointegrated dental implants without palatal mucosal grafts. Complications in
      group A were common and complex, unlike group B. All patients completed dental
      rehabilitation. CONCLUSIONS: Osseointegration was adequate to complete dental
      rehabilitation in group B without palatal mucosal grafts, but was significantly
      better in group A, and significantly best in group B with palatal mucosal grafts.
      Given the complexity and frequency of complications in group A, the authors
      recommend the double-barrel configuration with osseointegrated dental implants
      for segmental mandibular defect reconstruction. Palatal mucosal grafts have a
      definite advantage. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 25054247
TI  - Surgical treatment of head and neck port-wine stains by means of a staged zonal
      approach.
AB  - BACKGROUND: The majority of patients with capillary malformations (port-wine
      stains) develop soft-tissue and bony hypertrophy leading to gross facial
      asymmetry and functional deficits in vision, breathing, speech, and feeding. The
      authors describe and illustrate a surgical approach for the treatment of these
      malformations with restoration of facial symmetry and contour based on facial
      subunits. METHODS: The authors conducted a retrospective case series of patients
      from 2004 to 2011 presenting for primary evaluation and treatment to a tertiary
      referral center specializing in vascular anomalies. The medical records and
      photographs of patients with facial capillary malformations and soft-tissue
      hypertrophy were reviewed. RESULTS: Of the 160 patients who presented with the
      diagnosis of facial capillary malformation/port-wine stain, 96 (60 percent) had
      soft-tissue hypertrophy in one or more dermatomes resulting in facial asymmetry.
      Only 4.4 percent of patients had solely V1 involvement, 38.8 percent had V2
      involvement, and 15.6 percent had V3 involvement. The technique and incisions
      used for each facial zone are described in detail. In all cases, incisions were
      placed along existing boundaries of facial subunits. Serial pulsed-dye laser
      treatments were also performed. CONCLUSIONS: Sixty percent of patients with
      facial capillary malformation experience soft-tissue hypertrophy with or without
      bony remodeling, and surgical correction is required. The authors describe a
      staged surgical treatment for these patients based on a subunit and zonal
      approach to the face. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25054248
TI  - Tip extension suture: a new tool tailored for Asian rhinoplasty.
AB  - BACKGROUND: Recent changes in the release and rebuilding of the tripod structure
      during Asian rhinoplasty have allowed for additional lengthening and rotation of
      the nasal tip. To rebuild the nasal tip framework, we used the tip extension
      suture technique alone or in combination with other procedures. A retrospective,
      longitudinal study was conducted to evaluate the safety and efficacy of the tip
      extension suture technique for use in Asian rhinoplasty. METHODS: From May of
      2008 to December of 2011, 283 Asian patients underwent the tip extension suture
      technique and were postoperatively monitored for 6 months or longer. The tip
      extension suture surgical technique involves advancing the lateral crus, which is
      fully released from the pyriform margin-supported hinge areas, and fixing it to
      the caudal septum. The patients' medical charts and serial photographs were
      analyzed to assess outcome stability, complications (pinched deformity, skin
      necrosis, airway problems, or nasal valve collapse), patient satisfaction, and
      the need for revision surgery. RESULTS: This technique allowed most patients to
      retain an altered nasal tip shape during the follow-up period. The nasal tip was
      incompletely corrected in 14 patients (4.9 percent), and surgical revision owing
      to development of pinched deformities was required in eight patients (2.8
      percent). Ultimately, 92 percent of the patients were satisfied with their
      outcomes. Complications, such as circulation or airway problems, did not occur.
      CONCLUSION: This study describes and recommends a new tip extension suture
      procedure for rebuilding the released nasal tip framework during Asian
      rhinoplasty, with fewer aesthetic and functional complications. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25054249
TI  - Non-communicable disease surveillance and population surveys.

PMID- 25054250
TI  - Adolescent drivers in Brazil: prevalence and associated factors estimated from
      the National Adolescent School-based Health Survey (PeNSE 2012).
AB  - INTRODUCTION: There is evidence that adolescent drivers can represent risks to
      themselves, to passengers and to society in general. OBJECTIVE: To estimate the
      prevalence of history of driving among adolescent students (under the age of 18)
      and associated factors, in Brazil, in 2012. METHODS: This study analyzed data
      from the National Adolescent School-based Health Survey (PeNSE), held in 2012.
      The prevalence of history (at least once in the past 30 days) of driving
      motorized vehicles (cars, motorcycles or boats) by students aged less than 18
      years old, as well as crude and adjusted odds ratios (OR) related to frequent
      driving (four or more times in the past 30 days) as the outcome, were estimated.
      RESULTS: Among the 106,621 interviewed students, 27.0% (95%CI 22.9 - 31.5)
      reported having driven a motorized vehicle, and 12.9% (95%CI 10.0 - 16.5)
      reported being a frequent driver (four or more times). Factors associated with
      frequent driving were: older age, male, mothers with higher schooling, living in
      a household with fewer members, living in the North and Northeast regions, living
      with someone who has a motorcycle or a car, when their school is not located in a
      state-capital, drinking alcohol and not wearing a seatbelt. CONCLUSION: The
      higher prevalence of history of driving among adolescent students in Brazil and
      the identified associated factors might help authorities to prioritize policies
      and to reinforce the adherence to traffic legislation among specific groups.

PMID- 25054251
TI  - Labor in early life, vulnerability for health in Brazilian schoolchildren:
      National Adolescent School-based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: This study describes exposure labor among Brazilian 9th grade students
      from public and private schools and investigates socio-demographic
      characteristics, behaviors, violent situations and psychosocial factors
      associated with labor among adolescents. METHODS: The present study included
      108,984 students from the National Adolescent School-based Health Survey carried
      out in 2012. Variables were grouped into sociodemographic characteristics,
      behavioral factors, violent situations and psychosocial aspects. Associations
      between labor and several health risk variables were identified by multiple
      logistic regression analysis, after adjustment for sex and age. RESULTS:
      Approximately 13% of the students reported having a job: 17.4% of them were male.
      The chance of working was lower between females and individuals whose fathers'
      have incomplete superior education. Students who worked had greater chances to
      smoke (OR = 2.26; 95%CI 2.04 - 2.51), drink alcohol, use illicit drugs (OR =
      2.63; 95%CI 2.29 - 3.02), drive motorized vehicles (OR = 2.15; 95%CI 2.03 2.27),
      have sexual intercourse (OR = 2.10; 95%CI 1.99 - 2.24), suffer physical violence
      (OR = 1.57; 95%CI 1.46 1.68), engage in fights (OR = 1.65; 95%CI 1.55 - 1.76),
      feel lonely (OR = 1.26; 95%CI 1.17 - 1.36) and report sleeping problems (OR =
      1.46; 95%CI 1.34 - 1.60). They also have lower chances of having close friends
      (OR = 0.78; 95%CI 0.68 - 0.90). CONCLUSION: The prevalence of labor among
      students is high. Socioeconomical disadvantages increase the chances of early
      working. Early working is also associated to health damaging behavior, violent
      situations, sleeping problems, and social isolation. Adolescents who study and
      work experiment expositions that may affect distinct health dimensions and
      perpetuate disadvantages over lifetime.

PMID- 25054252
TI  - Lifetime use of illicit drugs and associated factors among Brazilian
      schoolchildren, National Adolescent School-based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: This study aimed at describing the prevalence of illicit drug use
      among 9th grade students in the morning period of public and private schools in
      Brazil, and assessing associated factors. METHOD: The Brazilian survey PeNSE
      (National Adolescent School-based Health Survey) 2012 evaluated a representative
      sample of 9th grade students in the morning period, in Brazil and its five
      regions. The use of illicit drugs at least once in life was assessed for the most
      commonly used drugs, such as marijuana, cocaine, crack, solvent-based glue,
      general ether-based inhalants, ecstasy and oxy. Data were subjected to
      descriptive analysis, and Pearson's chi2 test and logistic regression was used in
      the multivariate analysis. RESULTS: The use of illicit drugs at least once in
      life was reported by 7.3% (95%CI 5.3 - 9.4) of the respondents. Logistic
      regression was used for multivariate analysis and the evidences suggest that
      illicit drug use is associated to social conditions of greater consumption power,
      the use of alcohol and tobacco, behaviors related to socialization, such as
      having friends or sexual activity, and also the perception of loneliness, loose
      contact between school and parents and experiences of abuse in the family
      environment. The outcome was inversely associated with close contact with parents
      and parental supervision. CONCLUSION: In addition to the association with the
      processes of socialization and consumption, the influence of family and school is
      expressed in a particularly protective manner in different records of direct
      supervision and care.

PMID- 25054253
TI  - Psychoactive substance use, family context and mental health among Brazilian
      adolescents, National Adolescent School-based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: To evaluate the association between the consumption of psychoactive
      substances (tobacco, alcohol and illicit drugs) and demographic variables, mental
      health and family context among school-aged children. METHODS: The National
      Adolescent School-based Health Survey was held with a national sample of 109,104
      students. Data regarding demographic variables, family background and mental
      health were collected. Logistic regression was used to evaluate the associations
      of interest. RESULTS: Multivariate analyses showed that alcohol consumption was
      higher among girls, drug experimentation was more frequent among boys and that
      there was no difference between sexes for smoking. Being younger and mulatto were
      negatively associated with the use of tobacco, alcohol and illicit drugs. Also
      negatively associated with such risk behaviors were characteristics of the family
      context represented by: living with parents, having meals together and parental
      supervision (when parents know what the child does in their free time). Moreover,
      characteristics of mental health such as loneliness and insomnia were positively
      associated with use of tobacco, alcohol and illicit drugs. Not having friends was
      positively associated with use of tobacco and illicit drugs and negatively
      associated with alcohol use. CONCLUSIONS: The study shows the protective effect
      of family supervision in the use of tobacco, alcohol and drugs and, on the
      contrary, the increasing use of substances according to aspects of mental health,
      such as loneliness, insomnia and the fact of not having friends. The study's
      findings may support actions from health and education professionals, as well as
      from the government and families in order to prevent the use of these substances
      by adolescents.

PMID- 25054254
TI  - Experimentation and use of cigarette and other tobacco products among adolescents
      in the Brazilian state capitals (PeNSE 2012).
AB  - INTRODUCTION: Nicotine dependence establishes itself more rapidly among
      adolescents than among adults. Tobacco occupies the fourth place in the rank of
      main risk factors for non-communicable diseases in the continent. Studies reveal
      that other forms of tobacco use have increased among adolescents. METHODS: Were
      included the 9th grade students from the 26 State Capitals and the Federal
      District. who were participants of the National Adolescent School-based Health
      Survey (PeNSE), in 2012. Factors independently associated with experimentation
      and regular use of cigarettes were investigated by means of multinomial logistic
      regression, using as reference "never tried a cigarette". The use of other
      tobacco products included cigar, pipe, narghile and others. RESULTS: Of the in
      the 61,037 participants in the 26 Brazilian capitals and the Federal District,
      22.7% (95%CI 21.7 - 23.5) had experimented cigarettes, 6.1% (95%CI 5.6 - 6.6) are
      regular smokers and 7.1% (95%CI 6.5 - 7.7) had used other tobacco products, with
      half of them also being regular smokers. The chances of experimenting and being a
      regular smoker increased with age and according to the frequency of weekly
      exposure to other smokers. These chances were also higher among students who
      worked, who lived in monoparental families or without their parents, and those
      who felt that their parents would not mind if they smoked. CONCLUSION: Results
      reinforce the association between social disadvantages and experimenting and
      regular smoking. In addition, the use of other tobacco products is worthy of
      attention and may lead to regular smoking.

PMID- 25054255
TI  - Trend of the risk and protective factors of chronic diseases in adolescents,
      National Adolescent School-based Health Survey (PeNSE 2009 e 2012).
AB  - OBJECTIVE: To compare the prevalence of major risk and protection factors for
      chronic non-communicable diseases in school-aged children in Brazilian capitals
      surveyed in the National Adolescent School-based Health Survey in its two
      editions, 2009 and 2012. METHODS: The frequencies, with Confidence Interval of
      95%, of the following demographic variables were compared: food intake, body
      image, physical activity, smoking, alcohol and other drugs. Prevalence was
      compared in the two editions of the survey. RESULTS: The proportion of students
      who attend two physical education classes a week was maintained at 49% between
      2009 and 2012, increasing in public schools from 50.6% (95%CI 49.8 - 51.4) to
      52.5% (95%CI 49.2 - 55.7), and decreasing in private schools. There was no change
      in the proportion of students who watch two hours or more of television daily,
      about 80%. As for body image, there was no change between the two editions, and
      about 60% considered themselves being of normal weight. There was a reduction in
      the percentage of adolescents who experienced cigarettes, from 24.2% (95%CI 23.6 
      24.8) to 22.3% (95%CI 21.4 - 23.2), and the prevalence of smoking was maintained
      at about 6% (there was no statistical difference between 2009 and 2012). The
      consumption of beans, fruits, sweets and soft drinks also decreased. Frequency of
      drug experimentation was of 8.7% (95%CI 8.3 - 9.1) in 2009, and 9.6% (95%CI 9.0 -
      10.3) in 2012, with no difference between confidence intervals, and the frequency
      of alcohol experimentation was maintained at about 70%; the percentage of use in
      the past 30 days was also maintained at around 27%. CONCLUSION: In the Brazilian
      capitals, the vast majority of prevalence of risk factors were kept stable in the
      two editions of the National Survey of School. These data generate evidence to
      guide the implementation of public policies to minimize the exposure of
      adolescents to risk factors.

PMID- 25054256
TI  - Bullying in Brazilian school children: analysis of the National Adolescent School
      based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: To describe the victimization and bullying practice in Brazilian
      school children, according to data from the National Adolescent School-based
      Health Survey and to compare the surveys from 2009 and 2012. METHODS: This is a
      cross-sectional study with univariate and multivariate analyzes of the following
      variables: to have been treated badly by colleagues, to have been bullied and to
      have bullied other children. The following independent variables were analyzed:
      age, sex, race/color, type of school, maternal education. Prevalence rates were
      compared between the editions of 2009 and 2012 of the survey. RESULTS: Of all the
      adolescents analyzed, 27.5% have not been treated well by peers at school, with
      greater frequency among boys (OR = 1.50), at the age of 15 years (OR = 1.29) and
      16 (OR = 1.41), public school students (OR = 2.08), black (OR = 1.18) and whose
      mothers had less education; 7.2% reported having been bullied, with a greater
      chance in younger students (13 years old), male (OR = 1.26), black (OR = 1.15)
      and indigenous (OR = 1.16) and whose mothers had less education; 20.8% reported
      to have bullied other children, with a greater chance for older students, at the
      age of 14 (OR = 1.08) and 15 years (OR = 1.18), male (OR = 1.87), black (OR =
      1.14) and yellow (OR = 1.15), children of mothers with higher education, private
      school students. There was an increase of bullying in the Brazilian capitals,
      from 5.4 to 6.8%, between 2009 and 2012. DISCUSSION: The occurrence of bullying
      reveals that the Brazilian school context is also becoming a space of
      reproduction of violence, in which it is crucial to act intersectorally and to
      articulate social protection networks, aiming to face this issue.

PMID- 25054257
TI  - Prevalence of asthma symptoms among adolescents in Brazil: National Adolescent
      School-based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: This study aims to describe the prevalence rates of asthma symptoms in
      Brazil, its Regions and State capitals, according to data from the National
      Adolescent School-based Health Survey, 2012. Furthermore, it aims to compare the
      prevalence of asthma in the capitals evaluated by PeNSE 2012 with previous
      results of the International Study of Asthma and Allergies in Childhood (ISAAC).
      METHODS: Cross sectional study of 9th grade students at public and private
      schools of all Brazilian states and the Federal District (Brasilia). A self
      reported questionnaire containing items from the ISAAC was applied in order to
      identify the presence of asthma symptoms. RESULTS: The results of PeNSE indicate
      a high prevalence of asthma symptoms (23.2%) and of reports of a previous medical
      diagnosis of asthma (12.4%). Of the five state capitals in which the PeNSE
      results were compared to the ISAAC, Sao Paulo, Curitiba and Porto Alegre
      presented an increase in the prevalence of asthma symptoms. In Salvador, there
      was a reduction. CONCLUSION: Brazil is among the countries with the highest
      prevalence of asthma in the world, and the prevalence is still growing.

PMID- 25054258
TI  - Sexual behavior among Brazilian adolescents, National Adolescent School-based
      Health Survey (PeNSE 2012).
AB  - OBJECTIVE: This study describes the sexual behavior among students who
      participated in the National Adolescent School-based Health Survey (PeNSE) 2012
      and investigates whether social inequalities, the use of psychoactive substances
      and the dissemination of information on sexual and reproductive health in school
      are associated with differences in behavior. METHODOLOGY: The response variable
      was the sexual behavior described in three categories (never had sexual
      intercourse, had protected sexual intercourse, had unprotected sexual
      intercourse). The explanatory variables were grouped into socio- demographic
      characteristics, substance use and information on sexual and reproductive health
      in school. Variables associated with the conduct and unprotected sex were
      identified through multinomial logistic regression, using "never had sexual
      intercourse" as a reference. RESULTS: Over nearly a quarter of the adolescents
      have had sexual intercourse in life, being more frequent among boys. About 25%
      did not use a condom in the last intercourse. Low maternal education and work
      increased the chance of risky sexual behavior. Any chance of protected and
      unprotected sex increased with the number of psychoactive substances used. Among
      those who don't receive guidance on the prevention of pregnancy in school, the
      chance to have sexual intercourse increased, with the largest magnitude for
      unprotected sex (OR = 1.41 and OR = 1.87 ). CONCLUSION: The information on
      preventing pregnancy and STD/AIDS need to be disseminated before the 9th grade.
      Social inequalities negatively affect risky sexual behavior. Substance use is
      strongly associated with unprotected sex. Information on the prevention of
      pregnancy and STD/AIDS need to be disseminated early.

PMID- 25054259
TI  - Bullying and associated factors among Brazilian adolescents: analysis of the
      National Adolescent School-based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: To estimate the prevalence of bullying from the victim's perspective
      in Brazilian school children and to analyze its association with individual and
      family context variables. METHODS: An analysis of the data on 109,104
      adolescents, obtained by the National Adolescent School-based Health Survey, held
      in schools in 2012, was carried out. An association model between bullying and
      explanatory variables was tested in different contexts: sociodemographic, risk
      behaviors, mental health and family context. Univariate and multivariate analyzes
      were performed, calculating the Odds Ratio and confidence intervals. RESULTS: The
      prevalence of bullying found in this study was of 7.2% (95%CI 6.6 - 7.8). A
      higher chance of bullying was found among male students (OR = 1.58; 95%CI 1.51 -
      1.66), with an inverse relation between age and bullying, with the magnitude of
      risk among adolescents younger than 13 years of age being higher when compared to
      those with 16 years of age or more. Of individual risk behaviors, only being a
      smoker remained in the final model (OR = 1.11; 95%CI 1.01 - 1.23). Mental health
      variables associated with bullying were: feeling lonely (OR = 2.66; 95%CI 2.52 -
      2.81), insomnia (OR = 1.92; 95%CI 1.80 - 2.05), not having friends (OR = 1.71;
      95%CI 1.54 - 1.89), and, in the family context, those who skip class without
      telling their parents (OR = 1.13; 95%CI 1,07 - 1,19) and those who suffer
      physical abuse by family members (OR = 2.03; 95%CI 1.91 - 2.146). CONCLUSION:
      Bullying was associated to male students, younger, of black color, smokers, with
      mental health vulnerabilities and victims of domestic violence. This suggests the
      need for a holistic approach from education and health professionals, parents and
      the community in seeking measures for the prevention of bullying.

PMID- 25054260
TI  - Body image and extreme attitudes toward weight in Brazilian schoolchildren (PeNSE
      2012).
AB  - INTRODUCTION: Adolescence is a period characterized by changes such as
      accelerated physical growth and sexual development. Besides having to deal with
      these changes, adolescents are faced with beauty standards and extreme
      valorization of physical appearance. OBJECTIVE: This article aims to describe
      body image and the practice of extreme attitudes regarding weight in Brazilian
      students. METHODS: Data from the National Survey of School Health (PeNSE) 2012
      were used in this study. PeNSE 2012 has a representative sample of students in
      the 9th grade of elementary school in public and private schools across the
      country. A self-administered questionnaire on body image, practice of extreme
      measures in relation to weight and sociodemographic data was used. Body image and
      the practice of extreme attitudes were described for the total sample and
      according to gender. Poisson regression analyzes were used to identify
      differences in the practices of extreme attitudes between the different types of
      body image. RESULTS: More than 38% of the adolescents did not consider their body
      image as normal. Over 15% of the students referred to carry out extreme weight
      control practices, combining practices to loose and gain weight. Adolescents who
      considered themselves fat presented frequency of extreme practices for weight
      loss 92% higher than that shown by individuals who considered themselves normal.
      Similarly, adolescents who considered themselves thin presented frequency of
      extreme attitudes to gain weight (9.7%) higher than that shown by students who
      considered themselves normal (5.6%). CONCLUSIONS: The high frequency of extreme
      weight control practices among Brazilian adolescents is alarming and should be
      subject of measures in health and education fields.

PMID- 25054261
TI  - Situations of violence experienced by students in the state capitals and the
      Federal District: results from the National Adolescent School-based Health Survey
      (PeNSE 2012).
AB  - OBJECTIVE: To describe violent events experienced by school-aged adolescents in
      school, around the school and in the family context, and to compare the results
      of the National Adolescent School-based Health Survey of 2009 and 2012. METHODS:
      Indicators related to violence involving teenagers were analyzed. The prevalence
      rates and confidence intervals of 95% were calculated for events of interest
      according to gender and type of school (public or private) and regions. RESULTS:
      Prevalence rates were: insecurity in the route between home-school (9.1%),
      insecurity in school (8.0%), physical assault in the last 12 months (18.2%),
      engaging in fights in the last 12 months (20.7%), fighting with a cold weapon
      (8.3%), fighting with firearms (6.9%), physical assault by a family member
      (11.6%) and having been seriously injured in the last 12 months (10.3%). The
      situations of violence were more prevalent among male students from public
      schools. The comparison with the 2009 survey showed increased prevalence in all
      the variables studied. CONCLUSION: Teenagers are exposed to different forms of
      violence, and the data from the National Survey of School Health can support the
      planning of preventive actions.

PMID- 25054262
TI  - Sexual behavior of school-aged adolescents in the city of Goiania, Goias.
AB  - OBJECTIVE: To investigate the characteristics of sexual behavior in school-aged
      adolescents and possible differences regarding sex and type of school. METHODS:
      Cross-sectional study using data from the National Adolescent School-based Health
      Survey (PeNSE) 2009, carried out by the Brazilian Ministry of Health, in
      partnership with the Brazilian Institute of Geography and Statistics (IBGE). The
      sample consisted of 3,099 9th graders living in Goiania, State of Goias, Brazil,
      mostly aged between 13 to 15 years old, who answered a self-applicable
      questionnaire on risk and protective health factors. The Rao-Scott test was used
      in the statistical analysis, considering the complex sample design. RESULTS: The
      prevalence of sexual intercourse was of 26.5% (95%CI 23.8 - 29.4) at least once
      in life and of 18.5% (95%CI 16.5 - 20.8) in the last year. Both behaviors were
      more frequent among male students and among those attending public schools. Most
      of the respondents had their first intercourse at the age of 13 or younger, with
      up to 3 partners. They had also used a pregnancy prevention method in the last
      intercourse, and received guidance on prevention at school. The age of the first
      intercourse was earlier and the number of partners was higher among male
      students. More females and those attending public schools reported having
      received information on pregnancy prevention. Guidance on STD/AIDS was also more
      frequent in public schools. CONCLUSION: Results showed a need for health
      education measures involving education and health professionals, as well as
      parents, to reduce the discrepancies found regarding sex and type of school.

PMID- 25054263
TI  - Factors associated with injuries in adolescents, from the National Adolescent
      School-based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: To estimate the prevalence of injuries among teenagers and to examine
      the associated risk factors, such as sociodemographic characteristics, risk
      behaviors, family ties and other factors. METHOD: The prevalence of the outcome
      (injury) was estimated with a 95%confidence interval. In order to verify factors
      associated with the injury, a bivariate analysis was made with estimated odds
      ratio (OR) and its respective confidence intervals. Then, a multivariate analysis
      was carried out, only with variables whose descriptive level was equal to or
      lower than 5% (p < 0.05) remaining in the model. RESULTS: The study of injury in
      adolescents, based on the data from the National Adolescent School-based Health
      Survey (PeNSE), pointed out that 10.3% of the teenagers suffered severe injuries
      in the past 12 months, such as cuts or perforations, broken bones or dislocated
      joints. The following variables remained independently associated with "suffering
      severe injuries": being a male teenager; black, mulatto or indigenous race/color
      and working. Factors related to family ties are significant when the relations
      are fragile amongst members: adolescents that are injured the most are the ones
      who suffer most aggressions at home, who skip classes without notifying their
      parents, those who do not live with their parents and have low family control.
      The most relevant aspects of mental health are insomnia and loneliness. The
      factors associated to the exposure to situations of violence that remained in the
      model were: insecurity in school and in the route home-school; getting a ride
      with someone inebriated; drinking and driving motorized vehicles; not wearing the
      seatbelt; not wearing a helmet and being bullied. Among the factors of individual
      behavior, the following can be emphasized: use of alcohol, cigarettes, trying
      illicit drugs and early sexual intercourse. CONCLUSION: The analysis of the
      determinants for suffering injuries in childhood and adolescence shows the
      complex relationship between associated factors, which points to the need for
      action towards several aspects to reduce social inequalities, strengthen family
      ties and prevent violent contexts and individual risk factors.

PMID- 25054264
TI  - Alcohol consumption among Brazilian Adolescents according to the National
      Adolescent School-based Health Survey (PeNSE 2012).
AB  - OBJECTIVE: To describe the prevalence of alcohol consumption among Brazilian
      students and identify the sociodemographic factors associated alcohol consumption
      in the last 30 days. METHODS: Cross-sectional study with a cluster sample of
      109,104 9th grade students in Brazilian public and private schools in 2012. The
      prevalence and 95% confidence intervals of the indicators of alcohol consumption
      were analyzed. RESULTS: Of the students analyzed, 50.3% (95%CI 49.0 - 51.6)
      experimented one dose of alcoholic beverages or more. The consumption of alcohol
      in the last 30 days was 26.1% (95%CI 24.5 - 27.7), and there was no difference in
      prevalence between students from public and private schools. Drunkenness episodes
      were reported by 21.8% (95%CI 21.1 - 22.5) of the students. The perception of
      students about the negative reaction of their family if they came home drunk
      occurred in 89,7% (95%CI 89,6 - 89,9) of cases, and 10% (95%CI 8.9 - 11.1) of
      them reported having problems with their families or friends because they had
      been drinking. Among adolescents aged less than 14 years old, the first alcoholic
      drink intake was predominantly at 12 to 13 years old. The most common way to get
      a drink was at parties, with friends, buying in them in supermarkets, stores or
      bars and at home. The consumption of alcohol in the last 30 days was less
      frequent among boys, increasing with age. CONCLUSION: The study demonstrates the
      extension of alcohol as a problem, making it important to advance in measures
      such as the improvement of protective legislation for children and adolescents
      and stricter enforcement in alcohol sales.

PMID- 25054265
TI  - Prevalence of self-reported arterial hypertension in Brazilian capitals in 2011
      and analysis of its trends in the period between 2006 and 2011.
AB  - OBJECTIVE: To describe the prevalence of self-reported arterial hypertension in
      the adult population in the Brazilian state capitals and Federal District in
      2011, and analyze the trend from 2006 to 2011. METHODS: A time series study was
      conducted with data from the monitoring system by telephone survey (Vigitel) in
      the period between 2006 and 2011. Approximately 54,000 individuals were assessed
      per year in the locations studied. A polynomial regression model was used for
      trend analysis according to gender, age, education and region of the country.
      RESULTS: The prevalence of hypertension was 22.7% in 2011, higher in women
      (25.4%; 95%CI 24.2 - 26.5) than in men (19.5%; 95%CI 18.4 - 20.7). In the period
      between 2006 and 2011, the lower frequency of hypertension was observed in 2006
      (21.5%), and the higher in 2009 (24.4%), with no statistically significant
      difference in the period. CONCLUSION: There was no significant sex-specific
      trend, maintaining the higher frequency among women. The prevalence of
      hypertension increased progressively with age and was higher among adults with
      lower education (0 - 8 years of study). The South was the only region that showed
      a statistically significant increasing trend for the years between 2006 and 2011
      (15% per year).

PMID- 25054266
TI  - Analysis of care given to patients with hypertension in Belo Horizonte, according
      to telephone survey.
AB  - OBJECTIVE: To examine the care given to patients with hypertension in the
      Brazilian public and private health services in the population of Belo Horizonte,
      Minas Gerais. METHODS: Telephone interviews were conducted in a sample of
      hypertensive adults in the year 2009, in Belo Horizonte (n = 100). We compared
      the care provided to hypertensive users of the Unified Health System (SUS) and of
      the Supplementary Health (SS), using the chi2 test or Fisher's exact test. The
      prevalence ratio was calculated by the Poisson regression model, adjusted for the
      variables age, education and skin color. RESULTS: In the descriptive analysis,
      hypertensive users of private health plans had a higher frequency of physician
      referral and greater blood pressure control. Unified Health System users were the
      ones who participated in health promotion groups the most. The acquisition of
      antihypertensive medications by beneficiaries of private health insurance was
      more frequent in private pharmacies, and in Health Centers among users of the
      Unified Health System. The differences disappeared when adjusting the variables
      for age, race and education. There was no difference regarding the guidance
      received for a change of habits, or regarding the incorporation of these healthy
      practices promotion by hypertensive patients. CONCLUSION: A healthier diet, the
      practice of physical activity, and the non-use of alcohol and tobacco have been
      incorporated by hypertensive patients, whether owning private health insurance or
      not. Promotion practices, proper use of medication a clinical follow-up are
      important for the control of blood pressure levels.

PMID- 25054267
TI  - Comparison of risk and protective factors for chronic diseases in the population
      with and without health insurance in the Brazilian capitals, 2011.
AB  - INTRODUCTION: The article compares the risk and protective factors for Non
      communicable Diseases (NCD), referred morbidity and access to preventive
      examinations in the population with and without health insurance in all Brazilian
      State capitals. METHODS: The study population consists of adults (>= 18 years
      old) living in households with landlines in 26 Brazilian State capitals and the
      Federal District. Estimates of selected variables are presented according to
      possession of health plans ("Yes" or "No") and sex. A post-stratification was
      performed according to age, gender and education in both populations, and
      prevalence ratios were calculated, adjusted for age and sex between people with
      and without health insurance for the risk and protective factors for NCDs.
      RESULTS: A total of 54,099 people at the age of 18 or older were evaluated, 47.4%
      of them were beneficiaries of health plans. The coverage of health insurance
      tends to increase with age and level of education. Compared to non-beneficiaries
      of health plans, beneficiaries were more likely to have protective factors, such
      as healthy eating, physical activity, coverage tests, such as mammography and Pap
      test, and lower prevalence of risk factors such as smoking, physical inactivity,
      poor health assessment and hypertension. Alcohol abuse, consumption of
      excessively fat meats, overweight, obesity and diabetes were not associated with
      the variable possession of health insurance. When controlled by education,
      individuals who have health insurance generally have better indicators.
      CONCLUSION: This information is important to establish measures for reducing
      differences among people with and without health insurance.

PMID- 25054268
TI  - Utilization of public and private health services by the population of Belo
      Horizonte.
AB  - OBJECTIVE: To analyze the differences in health services utilization by users of
      Brazilian Unified Health System (SUS) and beneficiaries of Supplemental Health
      (SH). METHODS: A total of 288 adult subjects, residing in Belo Horizonte, who
      participated in the VIGITEL telephone survey in 2009, composed the sample, whose
      variables were analyzed according to the classification as users of SUS or
      beneficiaries of SH. Prevalence Ratios (PR), adjusted for sex, age and schooling,
      were calculated to evaluate differences between groups. RESULTS: Need and demand
      for health services were similar between groups, and users of SUS were less
      successful in obtaining service (PR = 0.78; p = 0.027). Most participants in both
      groups evaluated the health care received as very good/good without significant
      differences (72.1% for SUS, 84.0% for SH; p > 0.05). CONCLUSION: Although there
      are differences in the utilization of health services in Belo Horizonte, the
      service obtained is well rated by both users of SUS and health plans.

PMID- 25054269
TI  - Trends in prevalence of overweight and obesity in adults in 26 Brazilian state
      capitals and the Federal District from 2006 to 2012.
AB  - OBJECTIVE: To describe the annual evolution of the prevalence of overweight and
      obesity in the adult population of the 26 Brazilian state capitals and the
      Federal District from 2006 to 2012. METHODS: Annual interviews (around 54,000 per
      year) from VIGITEL (Surveillance System of Risk and Protective Factors for
      Chronic Non-Communicable Diseases through Telephone Interviews) were used. Self
      reported weight and height were used to estimate body mass index and nutritional
      status. Prevalence estimates of overweight and obesity are presented according to
      gender, age and schooling and to each city. Linear regression model was used to
      evaluate the time trend of prevalence. RESULTS: Prevalence of overweight in
      adults in the 27 cities monitored by VIGITEL increased from 43.2% (2006) to 51.0%
      (2012), with an annual increase rate of 1.37%. Prevalence of obesity increased
      from 11.6% to 17.4%, with an annual increase rate of 0.89%. The study showed a
      statistically significant increase in the prevalence of overweight in all cities,
      and for both genders, all age groups and all levels of schooling. Similar trends
      were also verified for obesity. CONCLUSIONS: If the trends verified from 2006 to
      2012 are maintained, in ten years, around two-thirds of the adults in Brazilian
      state capitals will be overweight, and a quarter will be obese. This perspective
      requests urgent response from government and intersectoral actions to combat the
      obesogenic environment.

PMID- 25054270
TI  - Fibroblast growth factor-inducible 14 regulates cell growth and multidrug
      resistance of small-cell lung cancer through the nuclear factor-kappaB pathway.
AB  - Fibroblast growth factor-inducible 14 (Fn14) has been reported to play an
      oncogene role in many types of cancer. However, its biological functions in small
      cell lung cancer (SCLC) remain unknown. The aim of this study is to investigate
      the roles of Fn14 in the cell growth and chemoresistance of SCLC and its possible
      molecular mechanism. Expression of Fn14 was examined in 51 cases of SCLC tissues
      by immunohistochemistry. Overexpression or knockdown of Fn14 was carried out in
      SCLC multidrug-resistant cell lines (H69AR and H446AR) and the parental cell
      lines (H69 and H446) to assess its influence on cell growth and chemoresistance.
      The results showed that Fn14 was expressed in 50.98% (26/51) of SCLC.
      Overexpression of Fn14 was associated with the poor pathologic stage of SCLC (P <
      0.05 by the Fisher's exact test) and the shorter survival time (by the Kaplan
      Meier method). Enforced expression of Fn14 in H69 and H446 cells promoted cell
      growth and enhanced multidrug resistance by decreasing cell apoptosis and
      increasing G2-phase cell accumulation. Inhibition of Fn14 expression using Fn14
      shRNA in H69AR and H446AR cells inhibited cell growth and sensitized cancer cells
      to chemotherapeutic drugs by increasing drug-induced cell apoptosis accompanied
      by G1, S phase arrest. Furthermore, elevated expression of Fn14 in H69 and H446
      cells can lead to increased expression of Bcl-xl and activity of nuclear factor
      kappaB (NF-kappaB). Similar results were observed by Fn14 knockdown H69AR and
      H446AR cells. Bcl-xl expression regulated by Fn14 was dependent on NF-kappaB
      activation. Our results suggest that Fn14 modulates cell growth and drug
      resistance by upregulating Bcl-xl expression through the NF-kappaB pathway. All
      findings provide insight into the Fn14 signaling mechanism and Fn14 may be a
      potentially novel target for interfering with cancer growth and chemoresistance
      in SCLC.

PMID- 25054271
TI  - Novel approaches to drug discovery for the treatment of type 2 diabetes.
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a chronic, complex and
      multifactorial metabolic disorder, which has become a serious global health
      problem. The side effects of known drugs and the deficiency of long-term safety
      data, in addition to the already determined adverse effects for the current
      preclinical drugs against T2DM, have largely called upon the urgent exploration
      of novel therapeutic and preventative strategies against this disease. AREAS
      COVERED: The authors highlight the potential approaches for anti-T2DM drug
      discovery by focusing on: the restoration of pancreatic beta-cell mass, the
      promotion of insulin secretion, the regulation of oxidative stress and
      endoplasmic reticulum (ER) stress and the modulation of autophagy. EXPERT
      OPINION: T2DM is based on the gradual development of insulin resistance and beta
      cell dysfunction. Thus, the restoration of beta-cell function is considered as
      one of the promising therapeutic strategies against T2DM. The stress factors,
      such as oxidative stress, ER stress and autophagy, play potent roles in the
      regulation of beta-cell apoptosis, insulin secretion and sensitivity in the
      development of T2DM involving complicated cross-talks. Based on multiplex stress
      involved regulatory networks, more and more novel potential targets have been
      discovered and the multi-targeted drug leads are expected to help develop more
      effective clinical agents for the treatment of T2DM.

PMID- 25054272
TI  - A case of gonococcal necrotising fasciitis.
AB  - This case report details the progress of a patient with severe disseminated
      gonococcal infection with associated necrotising fasciitis. His admission was
      punctuated by multiple surgical debridements and a prolonged intensive care stay
      due to multiple organ failure. An extended course of azithromycin-based
      antimicrobial therapy achieved a cure and the patient was eventually discharged
      home after 8 weeks. To our knowledge this is the first such case of
      histologically and microbiologically confirmed gonococcal necrotising fasciitis. 

PMID- 25054273
TI  - Generation of neutralizing monoclonal antibodies against a conformational epitope
      of human adenovirus type 7 (HAdv-7) incorporated in capsid encoded in a HAdv-3
      based vector.
AB  - The generation of monoclonal antibodies (MAbs) by epitope-based immunization is
      difficult because the immunogenicity of simple peptides is poor and T cells must
      be potently stimulated and immunological memory elicited. A strategy in which
      antigen is incorporated into the adenoviral capsid protein has been used
      previously to develop antibody responses against several vaccine targets and may
      offer a solution to this problem. In this study, we used a similar strategy to
      develop HAdv-7-neutralizing MAbs using rAdMHE3 virions into which hexon
      hypervariable region 5 (HVR5) of adenovirus type 7 (HAdv-7) was incorporated. The
      epitope mutant rAdMHE3 was generated by replacing HVR5 of Ad3EGFP, a recombinant
      HAdv-3-based vector expressing enhanced green fluorescence protein, with HVR5 of
      HAdv-7. We immunized BALB/c mice with rAdMHE3 virions and produced 22 different
      MAbs against them, four of which showed neutralizing activity against HAdv-7 in
      vitro. Using an indirect enzyme-linked immunosorbent assay (ELISA) analysis and
      an antibody-binding-competition ELISA with Ad3EGFP, HAdv-7, and a series of
      chimeric adenoviral particles containing epitope mutants, we demonstrated that
      the four MAbs recognize the neutralization site within HVR5 of the HAdv-7 virion.
      Using an immunoblotting analysis and ELISA with HAdv-7, recombinant peptides, and
      a synthetic peptide, we also showed that the neutralizing epitope within HVR5 of
      the HAdv-7 virion is a conformational epitope. These findings suggest that it is
      feasible to use a strategy in which antigen is incorporated into the adenoviral
      capsid protein to generate neutralizing MAbs. This strategy may also be useful
      for developing therapeutic neutralizing MAbs and designing recombinant vector
      vaccines against HAdv-7, and in structural analysis of adenoviruses.

PMID- 25054275
TI  - Cu(II)-ion-catalyzed solvolysis of N,N-bis(2-picolyl)ureas in alcohol solvents:
      evidence for cleavage involving nucleophilic addition and strong assistance of
      bis(2-picolyl)amine leaving group departure.
AB  - The kinetics and products for solvolysis of N-p-nitrophenyl-N',N'-bis(pyridin-2
      ylmethyl) urea (7a), N-methyl-N-p-nitrophenyl-N',N'-bis(pyridin-2-yl methyl) urea
      (7b), and N-phenyl-N',N'-bis(pyridin-2-yl-methyl) urea (DPPU) (7c) promoted by
      Cu(II) ion in methanol and ethanol were studied under (s)(s)pH-controlled
      conditions at 25  degrees C. Methanolysis and ethanolysis of these substrates
      proceeds rapidly at a 1:1 ratio of substrate:metal ion, the half-times for
      decomposition of the Cu(II):7a complexes being ~150 min in methanol and 15 min in
      ethanol. In all cases, the reaction products are the Cu(II) complex of bis(2
      picolyl)amine and the O-methyl or O-ethyl carbamate of the parent aniline,
      signifying that the point of cleavage is the bis(2-picolyl)-N-C=O bond. Reactions
      of the Cu(II):7b complexes in each solvent proceed about 3-5 times slower than
      their respective Cu(II):7a complexes, excluding an elimination mechanism that
      proceeds through an isocyanate which subsequently adds alcohol to give the
      observed products. The reactions also proceed in other solvents, with the order
      of reactivity ethanol > methanol >1-propanol >2-propanol > acetonitrile (with
      0.2% methanol) > water spanning a range of 150-fold. The mechanism of the
      reactions is discussed, and the reactivity and mode of cleavage are compared with
      that of the M(II)-promoted ethanolytic cleavage of a mono-2-picolyl derivative, N
      p-nitrophenyl-N'-(pyridin-2-yl-methyl) urea (4a), which had previously been shown
      to cleave at the aniline N-C=O bond. The large estimated acceleration of the rate
      of attack of ethoxide on 7b of at least 2 * 1016 provided by associating Cu(II)
      with the departing group in this urea is discussed in terms of a trifunctional
      role for the metal ion involving Lewis acid activation of the substrate,
      intramolecular delivery of a Cu(II)-coordinated ethoxide, and metal-ion-assisted
      leaving group departure.

PMID- 25054274
TI  - Immunomodulatory effects of high-protein diet with resveratrol supplementation on
      radiation-induced acute-phase inflammation in rats.
AB  - We hypothesized that a high-protein diet and/or resveratrol supplementation will
      improve acute inflammatory responses in rats after receiving experimental
      abdominal radiation treatment (ART). Based on our previous study, the period of
      10 days after ART was used as an acute inflammation model. Rats were exposed to a
      radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein
      diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At
      day 10 after ART, we measured profiles of lipids, proteins, and immune cells in
      blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and
      regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant
      disturbances of lipid profiles by increasing triglyceride (TG) and low-density
      lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein
      cholesterol. The proinflammatroy cytokine levels were also increased by ART. All
      the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of
      TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts
      were increased. In addition, the HP and [HP+RES] diets decreased the
      concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets
      decreased regulatory T cells compared with those of the control diet in ART
      group. Further, the HP diet led to a significant recovery of white blood cell
      counts, as well as increased percentages of lymphocyte and decreased percentages
      of neutrophils. In summary, RES appeared to be significantly effective in
      minimizing radiation-induced damage to lipid metabolism and immune responses. Our
      study also demonstrated the importance of dietary protein intake in recovering
      from acute inflammation by radiation.

PMID- 25054276
TI  - Differentiation of human umbilical cord mesenchymal stem cells into prostate-like
      epithelial cells in vivo.
AB  - Although human umbilical cord mesenchymal stem cells (hUC-MSCs) have been
      identified as a new source of MSCs for potential application in regenerative
      medicine, their full potential of differentiation has not been determined. In
      particular, whether they have the capability to differentiate into epithelial
      cells of endodermal origin such as the prostate epithelial cells is unknown. Here
      we report that when hUC-MSCs were combined with rat urogenital sinus stromal
      cells (rUGSSs) and transplanted into the renal capsule in vivo, they could
      differentiate into prostate epithelial-like cells that could be verified by
      prostate epithelial cell-specific markers including the prostate specific
      antigen. The prostatic glandular structures formed in vivo displayed similar
      cellular architecture with lumens and branching features as seen for a normal
      prostate. In addition, the human origin of the hUC-MSCs was confirmed by
      immunocytochemistry for human nuclear antigen. These findings together indicate
      that hUC-MSCs have the capability to differentiate into epithelial-like cells
      that are normally derived from the endoderm, implicating their potential
      applications in tissue repair and regeneration of many endoderm-derived internal
      organs. 

PMID- 25054277
TI  - Prevalence of amyotrophic lateral sclerosis - United States, 2010-2011.
AB  - PROBLEM/CONDITION: Amyotrophic lateral sclerosis (ALS), commonly known as Lou
      Gehrig's disease, is a progressive and fatal neuromuscular disease for which no
      cure has been identified. Although ALS has no known definitive cause, familial
      ALS (a hereditary form) occurs in 5%-10% of cases. Many hypotheses have been
      formulated about what causes ALS, including chemical exposures, occupational
      exposure, military service, infectious agents, nutritional intake, physical
      activity, and trauma. Worldwide, ALS affects white males aged >60 years more
      often than any other group. In the United States, ALS surveillance is necessary
      to estimate the incidence and prevalence of ALS and collect data on risk factors.
      ALS is not a nationally notifiable condition in the United States (i.e., it is
      not a reportable condition in all jurisdictions), and individual state reporting
      requirements differ, with Massachusetts being the only state that mandates
      reporting. PERIOD COVERED: October 19, 2010-December 31, 2011. DESCRIPTION OF
      SYSTEM: In 2009, the federal Agency for Toxic Substances and Disease Registry
      (ATSDR) implemented the National ALS Registry to collect and analyze data
      regarding persons with ALS in the United States. The main goals of the Registry,
      as defined by the 2008 ALS Registry Act, are to describe the incidence and
      prevalence of ALS better, examine risk factors such as environmental and
      occupational exposures, and characterize the demographics of those living with
      ALS. The Registry uses a two-pronged approach to identify all cases of ALS. The
      first approach uses four existing national administrative databases (maintained
      by Medicare, Medicaid, the Veterans Health Administration, and the Veterans
      Benefits Administration) to identify prevalence of ALS. The second approach uses
      a secure web portal (http://www.cdc.gov/als) that was launched to the public on
      October 19, 2010, to identify cases not included in the four national
      administrative databases and to collect risk-factor data on known ALS cases. ALS
      patients who have registered via the web portal can complete brief risk-factor
      surveys online that are intended to attain a better understanding of ALS (e.g.,
      genetics and environmental and occupational exposures) and help determine disease
      progression. RESULTS: During October 19, 2010-December 31, 2011, a total of
      12,187 persons meeting the surveillance case definition of definite ALS were
      identified by the Registry, for a prevalence of 3.9 cases of ALS per 100,000
      persons in the U.S. general population. Incidence cannot be measured because the
      date of diagnosis was not noted in all patient records. Overall, ALS was more
      common among white males, non-Hispanics, and persons aged 60-69 years. The age
      groups with the lowest number of persons with ALS were age 18-39 years and age
      >80 years. Males had a higher prevalence rate of ALS than females overall and
      across all data sources. INTERPRETATION: This is the first (and to date the only)
      effort to estimate the national prevalence of ALS in the United States. Using the
      combined approach of the national databases and the web-based portal enables
      researchers to estimate ALS prevalence more accurately. Registry findings for the
      prevalence of ALS are consistent with findings from long-established ALS
      registries in Europe and from smaller-scale epidemiologic studies conducted
      previously in the United States. Although incidence cannot be measured with
      Registry data at this time, incidence is being measured in smaller geographic
      areas that have participated in ATSDR's State and Metropolitan Area ALS
      surveillance projects. PUBLIC HEALTH ACTIONS: Data collected by the National ALS
      Registry are being used to better describe the prevalence of ALS in the United
      States and to help facilitate research. The combined approach of using national
      administrative databases and a self-enrollment web portal to collect data is
      novel and potentially could be used for other non-notifiable diseases such as
      Parkinson's disease or multiple sclerosis. ATSDR is working closely with ALS
      advocacy and support groups, researchers, health-care professionals, and others
      to promote the National ALS Registry in order to capture all cases of ALS. To
      further enhance and strengthen the Registry, ATSDR is 1) adding new modules to
      the portal to examine other potential risk factors, 2) launching a feasibility
      study for a novel ALS biorepository (available at
      http://wwwn.cdc.gov/als/ALSBioRegistry.aspx) linked to the Registry that would
      potentially provide biologic specimens from patient enrollees to help researchers
      learn more about disease etiology, 3) engaging in surveillance activities in
      selected states and large metropolitan areas to help test the completeness of the
      Registry as well as calculating incidence in these areas, and 4) using the
      Registry to recruit patient enrollees for new clinical trials and epidemiologic
      studies. Additional information about the National ALS Registry is available at
      http://www.cdc.gov/als or by calling toll-free at 1-877-442-9719.

PMID- 25054278
TI  - Case series of laser-assisted treatment of excessive gingival display: an
      alternative treatment.
AB  - OBJECTIVE: The objective of this study was to investigate the stable and
      significant outcomes of laser-assisted lip repositioning technique for the
      treatment of excessive gingival display. BACKGROUND DATA: "Gummy smile" is a
      major concern for a large number of patients visiting the dentist. The
      hyperactivity of the upper lip is one of the main causes of a gummy smile, and
      several techniques have been proposed for its treatment. METHODS: Ten patients
      with excessive gingival display were treated with laser-assisted lip
      repositioning technique. The technique is composed of removing a strip of mucosa
      by laser incisions from the maxillary buccal vestibule, and coronal repositioning
      of the new mucosal margin. The clinical dimensions of gingival display were
      measured from the left, right posterior, and anterior sides at baseline, 6 and 12
      months postoperatively. Subjects completed surveys to evaluate satisfaction with
      outcomes. Clinical and patient-centered parameters [visual analog scale for pain
      and aesthetics (VAS)] were measured at 7 days and again at 12 months after the
      surgery. RESULTS: The baseline anterior gingival display of 4.3+/-1.8 mm
      significantly decreased to 1.1+/-1.0 mm at 6 months (p<0.0001) and was maintained
      at 12 months (1.2+/-1.5 mm). The baseline left, right gingival display (4.9+/-2.2
      mm; 5.0+/-1.4 mm) significantly decreased (1.2+/-1.4 mm; 1.3+/-1.1 mm) at 12
      months (p<0.0001). Patients were satisfied with their smile after surgery and
      would likely choose to undergo the procedure again. CONCLUSIONS: The treatment of
      gummy smile with laser-assisted lip repositioning successfully reduced the
      preoperative gingival display without postoperative complications, in all cases.

PMID- 25054279
TI  - Platelet-rich plasma and skeletal muscle healing: a molecular analysis of the
      early phases of the regeneration process in an experimental animal model.
AB  - Platelet-rich plasma (PRP) has received increasing interest in applied medicine,
      being widely used in clinical practice with the aim of stimulating tissue
      healing. Despite the reported clinical success, there is still a lack of
      knowledge when considering the biological mechanisms at the base of the activity
      of PRP during the process of muscle healing. The aim of the present study was to
      verify whether the local delivery of PRP modulates specific molecular events
      involved in the early stages of the muscle regeneration process. The right flexor
      sublimis muscle of anesthetized Wistar rats was mechanically injured and either
      treated with PRP or received no treatment. At day 2 and 5 after surgery, the
      animals were sacrificed and the muscle samples evaluated at molecular levels. PRP
      treatment increased significantly the mRNA level of the pro-inflammatory
      cytokines IL-1beta, and TGF-beta1. This phenomenon induced an increased
      expression at mRNA and/or protein levels of several myogenic regulatory factors
      such as MyoD1, Myf5 and Pax7, as well as the muscular isoform of insulin-like
      growth factor1 (IGF-1Eb). No effect was detected with respect to VEGF-A
      expression. In addition, PRP application modulated the expression of miR-133a
      together with its known target serum response factor (SRF); increased the
      phosphorylation of alphaB-cristallin, with a significant improvement in several
      apoptotic parameters (NF-kappaB-p65 and caspase 3), indexes of augmented cell
      survival. The results of the present study indicates that the effect of PRP in
      skeletal muscle injury repair is due both to the modulation of the molecular
      mediators of the inflammatory and myogenic pathways, and to the control of
      secondary pathways such as those regulated by myomiRNAs and heat shock proteins,
      which contribute to proper and effective tissue regeneration.

PMID- 25054280
TI  - Suicide and the 2008 economic recession: who is most at risk? Trends in suicide
      rates in England and Wales 2001-2011.
AB  - The negative impacts of previous economic recessions on suicide rates have
      largely been attributed to rapid rises in unemployment in the context of
      inadequate social and work protection programmes. We have investigated trends in
      indicators of the 2008 economic recession and trends in suicide rates in England
      and Wales in men and women of working age (16-64 years old) for the period 2001
      2011, before, during and after the economic recession, our aim was to identify
      demographic groups whose suicide rates were most affected. We found no clear
      evidence of an association between trends in female suicide rates and indicators
      of economic recession. Evidence of a halt in the previous downward trend in
      suicide rates occurred for men aged 16-34 years in 2006 (95% CI Quarter 3 (Q3)
      2004, Q3 2007 for 16-24 year olds & Q1 2005, Q4 2006 for 25-34 year olds), whilst
      suicide rates in 35-44 year old men reversed from a downward to upward trend in
      early 2010 (95% CI Q4 2008, Q2 2011). For the younger men (16-34 years) this
      change preceded the sharp increases in redundancy and unemployment rates of early
      2008 and lagged behind rising trends in house repossessions and bankruptcy that
      began around 2003. An exception were the 35-44 year old men for whom a change in
      suicide rate trends from downwards to upwards coincided with peaks in
      redundancies, unemployment and rises in long-term unemployment. Suicide rates
      across the decade rose monotonically in men aged 45-64 years. Male suicide in the
      most-to-medium deprived areas showed evidence of decreasing rates across the
      decade, whilst in the least-deprived areas suicide rates were fairly static but
      remained much lower than those in the most-deprived areas. There were small post
      recession increases in the proportion of suicides in men in higher
      management/professional, small employer/self-employed occupations and fulltime
      education. A halt in the downward trend in suicide rates amongst men aged 16-34
      years, may have begun before the 2008 economic recession whilst for men aged 35
      44 years old increased suicide rates mirrored recession related unemployment.
      This evidence suggests indicators of economic strain other than unemployment and
      redundancies, such as personal debt and house repossessions may contribute to
      increased suicide rates in younger-age men whilst for men aged 35-44 years old
      job loss and long-term unemployment is a key risk factor. 

PMID- 25054281
TI  - Linking governance mechanisms to health outcomes: a review of the literature in
      low- and middle-income countries.
AB  - We conducted a synthesis of peer-reviewed literature to shed light on links
      between governance mechanisms and health outcomes in low- and middle-income
      countries. Our review yielded 30 studies, highlighting four key governance
      mechanisms by which governance may influence health outcomes in these settings:
      Health system decentralization that enables responsiveness to local needs and
      values; health policymaking that aligns and empowers diverse stakeholders;
      enhanced community engagement; and strengthened social capital. Most, but not
      all, studies found a positive association between governance and health.
      Additionally, the nature of the association between governance mechanisms and
      health differed across studies. In some studies (N = 9), the governance effect
      was direct and positive, while in others (N = 5), the effect was indirect or
      modified by contextual factors. In still other studies (N = 4), governance was
      found to have a moderating effect, indicating that governance mechanisms
      influenced other system processes or structures that improved health. The
      remaining studies reported mixed findings about the association between
      governance and health (N = 6), no association between governance and health (N =
      4), or had inconclusive results (N = 2). Further exploration is needed to fully
      understand the relationship between governance and health and to inform the
      design and delivery of evidence-based, effective governance interventions around
      the world. 

PMID- 25054282
TI  - Association of lifetime intellectual enrichment with cognitive decline in the
      older population.
AB  - IMPORTANCE: Intellectual lifestyle enrichment throughout life is increasingly
      viewed as a protective strategy against commonly observed cognitive decline in
      the older population. OBJECTIVES: To investigate the association of lifetime
      intellectual enrichment with baseline cognitive performance and rate of cognitive
      decline in an older population without dementia and to estimate the years of
      protection provided against cognitive impairment by these factors. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective analysis of individuals enrolled from
      October 1, 2004, and in 2008 and 2009 in the Mayo Clinic Study of Aging, a
      longitudinal, population-based study of cognitive aging in Olmsted County,
      Minnesota. We studied 1995 individuals without dementia (1718 cognitively normal
      individuals and 277 individuals with mild cognitive impairment) who completed
      intellectual lifestyle enrichment measures at baseline and underwent at least 1
      follow-up visit. MAIN OUTCOMES AND MEASURES: We studied the effect of lifetime
      intellectual enrichment by separating the variables into 2 nonoverlapping
      principal components: education/occupation score and mid/late-life cognitive
      activity based on self-report questionnaires. A global cognitive z score served
      as the summary cognition measure. Linear mixed-effects models were used to
      investigate the associations of demographic and intellectual enrichment measures
      with global cognitive z score trajectories. RESULTS: Baseline cognitive
      performance was lower in older individuals; individuals with lower
      education/occupation score, lower mid/late-life cognitive activity, and APOE
      genotype; and men (P < .001). The interaction between the 2 intellectual
      enrichment measures was significant (P < .03) such that the beneficial effect of
      mid/late-life cognitive activity on baseline cognitive performance was reduced
      with increasing education/occupation score. Only baseline age, mid/late-life
      cognitive activity, and APOE4 genotype were significantly associated with
      longitudinal change in cognitive performance from baseline (P < .05). For APOE4
      carriers with high lifetime intellectual enrichment (75th percentile of
      education/occupation score and midlife to late-life cognitive activity), the
      onset of cognitive impairment was approximately 8.7 years later compared with low
      lifetime intellectual enrichment (25th percentile of education/occupation score
      and mid/late-life cognitive activity). CONCLUSIONS AND RELEVANCE: Higher
      education/occupation scores were associated with higher levels of cognition.
      Higher levels of mid/late-life cognitive activity were also associated with
      higher levels of cognition, but the slope of this association slightly increased
      over time. Lifetime intellectual enrichment might delay the onset of cognitive
      impairment and be used as a successful preventive intervention to reduce the
      impending dementia epidemic.

PMID- 25054284
TI  - A model for the prediction of droplet size in Pickering emulsions stabilized by
      oppositely charged particles.
AB  - Colloidal particles irreversibly adsorb at fluid-fluid interfaces stabilizing
      what are commonly called "Pickering" emulsions and foams. A simple geometrical
      model, the limited coalescence model, was earlier proposed to estimate droplet
      sizes in emulsions. This model assumes that all of the particles are effective in
      stabilization. The model predicts that the average emulsion drop size scales
      inversely with the total number of particles, confirmed qualitatively with
      experimental data on Pickering emulsions. In recent years, there has been an
      increasing interest in synthesizing emulsions with oppositely charged particles
      (OCPs). In our experimental study, we observed that the drop size varies
      nonmonotonically with the number ratio of oppositely charged colloids, even when
      a fixed total number concentration of colloids is used, showing a minimum. We
      develop a mathematical model to predict this dependence of drop size on number
      ratio in such a mixed particle system. The proposed model is based on the
      hypothesis that oppositely charged colloids form stable clusters due to the
      strong electrostatic attraction between them and that these clusters are the
      effective stabilizing agents. The proposed model is a two-parameter model,
      parameters being the ratio of effective charge of OCPs (denoted as k) and the
      size of the aggregate containing X particles formed due to aggregation of OCPs.
      Because the size of aggregates formed during emulsification is not directly
      measurable, we use suitable values of parameters k and X to best match the
      experimental observations. The model predictions are in qualitative agreement
      with experimentally observed nonmonotonic variation of droplet sizes. Using
      experiments and theory, we present a physical insight into the formation of OCP
      stabilized Pickering emulsions. Our model upgrades the existing Wiley's limited
      coalescence model as applied to emulsions containing a binary mixture of
      oppositely charged particles. 

PMID- 25054283
TI  - Transplantation of induced pluripotent stem cells improves functional recovery in
      Huntington's disease rat model.
AB  - The purpose of this study was to determine the functional recovery of the
      transplanted induced pluripotent stem cells in a rat model of Huntington's
      disease with use of 18F-FDG microPET/CT imaging. METHODS: In a quinolinic acid
      induced rat model of striatal degeneration, induced pluripotent stem cells were
      transplanted into the ipsilateral lateral ventricle ten days after the quinolinic
      acid injection. The response to the treatment was evaluated by serial 18F-FDG
      PET/CT scans and Morris water maze test. Histological analyses and Western
      blotting were performed six weeks after stem cell transplantation. RESULTS: After
      induced pluripotent stem cells transplantation, higher 18F-FDG accumulation in
      the injured striatum was observed during the 4 to 6-weeks period compared with
      the quinolinic acid-injected group, suggesting the metabolic recovery of injured
      striatum. The induced pluripotent stem cells transplantation improved learning
      and memory function (and striatal atrophy) of the rat in six week in the
      comparison with the quinolinic acid-treated controls. In addition,
      immunohistochemical analysis demonstrated that transplanted stem cells survived
      and migrated into the lesioned area in striatum, and most of the stem cells
      expressed protein markers of neurons and glial cells. CONCLUSION: Our findings
      show that induced pluripotent stem cells can survive, differentiate to functional
      neurons and improve partial striatal function and metabolism after implantation
      in a rat Huntington's disease model.

PMID- 25054285
TI  - Combinatorial roles of heparan sulfate proteoglycans and heparan sulfates in
      Caenorhabditis elegans neural development.
AB  - Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and
      adult physiology of all metazoan organisms. Most of the known molecular
      interactions of HSPGs are attributed to the structurally highly complex heparan
      sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan)
      contains HS modifications that differ from another HSPG (such as glypican) has
      remained largely unresolved. Here, a neural model in C. elegans is used to
      demonstrate for the first time the relationship between specific HSPGs and HS
      modifications in a defined biological process in vivo. HSPGs are critical for the
      migration of hermaphrodite specific neurons (HSNs) as genetic elimination of
      multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic
      elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the
      migrating neuron and in the matrix, act in parallel to support neuron migration.
      Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6,
      function in a linear signaling pathway and glypican/lon-2 and HS 2-O
      sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1
      and hst-6. These results suggest core protein specific HS modifications that are
      critical for HSN migration. In C. elegans, the core protein specificity of
      distinct HS modifications may be in part regulated at the level of tissue
      specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic
      analysis reveals that there is a delicate balance of HS modifications and
      eliminating one HS modifying enzyme in a compromised genetic background leads to
      significant changes in the overall phenotype. These findings are of importance
      with the view of HS as a critical regulator of cell signaling in normal
      development and disease. 

PMID- 25054286
TI  - Ecological shifts in Mediterranean coralligenous assemblages related to gorgonian
      forest loss.
AB  - Mediterranean gorgonian forests are threatened by several human activities and
      are affected by climatic anomalies that have led to mass mortality events in
      recent decades. The ecological role of these habitats and the possible
      consequence of their loss are poorly understood. Effects of gorgonians on the
      recruitment of epibenthic organisms were investigated by manipulating presence of
      gorgonians on experimental panels at 24 m depth, for Eunicella cavolinii, and at
      40 m depth, for Paramuricea clavata, at two sites: Tavolara Island (Tyrrhenian
      Sea) and Portofino Promontory (Ligurian Sea). After 4 months, the most abundant
      taxa on the panels were encrusting green algae, erect red algae and crustose
      coralline algae at 24 m depth and encrusting brown algae and erect red algae at
      40 m depth. Assemblages on the panels were significantly affected by the presence
      of the gorgonians, although effects varied across sites and between gorgonian
      species. Species diversity and evenness were lower on panels with gorgonian
      branches. Growth of erect algae and recruitment of serpulid polychaetes were also
      affected by the presence of the gorgonians, primarily at Tavolara. Crustose
      coralline algae and erect sponges were more abundant on E. cavolinii panels at 24
      m depth, while encrusting bryozoans were more abundant on P. clavata panels at 40
      m depth. Effects of gorgonians on recruited assemblages could be due to
      microscale modification of hydrodynamics and sediment deposition rate, or by a
      shading effect reducing light intensity. Gorgonians may also intercept settling
      propagules, compete for food with the filter-feeders and/or for space by
      producing allelochemicals. Presence of gorgonians mainly limits the growth of
      erect algae and enhances the abundance of encrusting algae and sessile
      invertebrates. Therefore, the gorgonian disappearances may cause a shift from
      assemblages characterised by crustose coralline algae to filamentous algae
      assemblages, decreasing complexity and resilience of coralligenous
      bioconstructions. 

PMID- 25054288
TI  - Impaired perception of facial motion in autism spectrum disorder.
AB  - Facial motion is a special type of biological motion that transmits cues for
      socio-emotional communication and enables the discrimination of properties such
      as gender and identity. We used animated average faces to examine the ability of
      adults with autism spectrum disorders (ASD) to perceive facial motion.
      Participants completed increasingly difficult tasks involving the discrimination
      of (1) sequences of facial motion, (2) the identity of individuals based on their
      facial motion and (3) the gender of individuals. Stimuli were presented in both
      upright and upside-down orientations to test for the difference in inversion
      effects often found when comparing ASD with controls in face perception. The ASD
      group's performance was impaired relative to the control group in all three tasks
      and unlike the control group, the individuals with ASD failed to show an
      inversion effect. These results point to a deficit in facial biological motion
      processing in people with autism, which we suggest is linked to deficits in lower
      level motion processing we have previously reported. 

PMID- 25054291
TI  - Biomarkers usher in era of personalized care for malignant glioma patients.

PMID- 25054289
TI  - Mitochondria-targeted catalase reverts the neurotoxicity of hSOD1G93A astrocytes
      without extending the survival of ALS-linked mutant hSOD1 mice.
AB  - Dominant mutations in the Cu/Zn-superoxide dismutase (SOD1) cause familial forms
      of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the
      progressive loss of motor neurons. The molecular mechanism underlying the toxic
      gain-of-function of mutant hSOD1s remains uncertain. Several lines of evidence
      suggest that toxicity to motor neurons requires damage to non-neuronal cells. In
      line with this observation, primary astrocytes isolated from mutant hSOD1 over
      expressing rodents induce motor neuron death in co-culture. Mitochondrial
      alterations have been documented in both neuronal and glial cells from ALS
      patients as well as in ALS-animal models. In addition, mitochondrial dysfunction
      and increased oxidative stress have been linked to the toxicity of mutant hSOD1
      in astrocytes and neurons. In mutant SOD1-linked ALS, mitochondrial alterations
      may be partially due to the increased association of mutant SOD1 with the outer
      membrane and intermembrane space of the mitochondria, where it can affect several
      critical aspects of mitochondrial function. We have previously shown that
      decreasing glutathione levels, which is crucial for peroxide detoxification in
      the mitochondria, significantly accelerates motor neuron death in hSOD1G93A mice.
      Here we employed a catalase targeted to the mitochondria to investigate the
      effect of increased mitochondrial peroxide detoxification capacity in models of
      mutant hSOD1-mediated motor neuron death. The over-expression of mitochondria
      targeted catalase improved mitochondrial antioxidant defenses and mitochondrial
      function in hSOD1G93A astrocyte cultures. It also reverted the toxicity of
      hSOD1G93A-expressing astrocytes towards co-cultured motor neurons, however ALS
      animals did not develop the disease later or survive longer. Hence, while
      increased oxidative stress and mitochondrial dysfunction have been extensively
      documented in ALS, these results suggest that preventing peroxide-mediated
      mitochondrial damage alone is not sufficient to delay the disease.

PMID- 25054292
TI  - Metabolism and glioma therapy.

PMID- 25054293
TI  - Chemoprotection in glioblastoma therapy: reality or a dream?

PMID- 25054296
TI  - Ask the Experts: How best to treat recurrent glioma.

PMID- 25054297
TI  - Interview: Improving outcome for brain tumor patients.

PMID- 25054298
TI  - Brain metastases as a cause of malignant cerebrospinal fluid ascites: case report
      and review of the literature.
AB  - The development of cerebrospinal fluid ascites after a ventriculo-peritoneal
      shunt operation is an extremely rare complication. There have been only sporadic
      case reports and small series reviews published in regards to this condition.
      They are usually found in the context of primary brain tumors, usually affecting
      the pediatric population. We present an unusual case of a patient with known
      metastatic breast carcinoma to the brain who develops malignant cerebrospinal
      fluid ascites after a ventriculo-peritoneal shunt insertion. This is the first
      known adult case of a metastatic breast primary to the brain causing tumor
      dissemination via a ventriculo-peritoneal shunt.

PMID- 25054299
TI  - Supportive follow-up in patients treated with radical intent for high-grade
      glioma.
AB  - Ongoing supportive follow-up for patients with malignant glioma lacks good
      evidence to define and guide practice, and certain approaches have previously
      been criticized. In the UK, it commonly involves routine hospital visits with
      imaging to monitor treatment effects and detect disease progression. AIMS:
      Through use of an observational study evaluate and compare oncologist-led follow
      up with a multidisciplinary group follow-up method from the perspective of
      patients and caregivers. MATERIALS & METHODS: A total of 40 patients, and 32 of
      their caregivers, were recruited 3 months after completing radical radiotherapy
      treatment. Face-to-face interviews conducted at home with patients gathered
      information about access to and experiences of follow-up services. Standardized
      questionnaires measured patients' quality of life and unmet care needs, and
      caregivers' psychological wellbeing. Assessment was repeated three times over a 6
      month period. RESULTS: Inevitable attrition left 26/40 patients and 19/32
      caregivers with complete data. Most (65%) patients' quality of life improved or
      was maintained over the study period. However, psychological support for patients
      and caregivers was suboptimal, notably 56% of caregivers had probable psychiatric
      morbidity. Though few significant differences were found between the two follow
      up methods, multidisciplinary follow-up provided better continuity of care and
      more efficient test result provision. CONCLUSION: Innovative interventions are
      required to ameliorate psychological distress in patients and caregivers.

PMID- 25054300
TI  - State of the art and perspectives in the treatment of glioblastoma.
AB  - Glioblastoma is the most common malignant primary brain tumor. Cures are rare and
      median survival varies from several to 22 months. Standard treatment for good
      performance patients consists of maximal safe surgical resection followed by
      radiotherapy with concurrent temozolomide (TMZ) chemotherapy and six cycles of
      postradiotherapy TMZ. At recurrence, treatment options include repeat surgery
      (with or without Gliadel wafer placement), reirradiation or systemic therapy.
      Most patients with good performance status are treated with cytotoxic
      chemotherapy or targeted biologic therapy following or in lieu of repeat surgery.
      Cytotoxic chemotherapy options include nitrosoureas, rechallenge with TMZ,
      platins, phophoramides and topoisomerase inhibitors, although efficacy is
      limited. Despite the intense effort of developing biologic agents that target
      angiogenesis and growth and proliferative pathways, bevacizumab is the only agent
      that has shown efficacy in clinical trials. It was awarded accelerated approval
      in the USA after demonstrating an impressive radiographic response in two open
      label, prospective Phase II studies. Two randomized, Phase III trials of upfront
      bevacizumab have completed and may demonstrate survival benefit; however, results
      are pending at this time. Given the limited treatment options at tumor
      recurrence, consideration for enrollment on a clinical trial is encouraged.

PMID- 25054301
TI  - Awake craniotomy for supratentorial gliomas: why, when and how?
AB  - Awake craniotomy has become an increasingly utilized procedure in the treatment
      of supratentorial intra-axial tumors. The popularity of this procedure is
      partially attributable to improvements in intraoperative technology and
      anesthetic techniques. The application of awake craniotomy to the field of neuro
      oncology has decreased iatrogenic postoperative neurological deficits, allowed
      for safe maximal tumor resection and improved healthcare resource stewardship by
      permitting early patient discharge. In this article, we review recent evidence
      for the utility of awake craniotomy in the resection of gliomas and describe the
      senior author's experience in performing this procedure. Furthermore, we explore
      innovative applications of awake craniotomy to outpatient tumor resections and
      the conduct of neurosurgery in resource-poor settings. We conclude that awake
      craniotomy is an effective and versatile neurosurgical procedure with expanding
      applications in neuro-oncology.

PMID- 25054302
TI  - The potential of PARP inhibitors in neuro-oncology.
AB  - DNA damaging agents have an integral role in the treatment of brain tumors.
      Recent advances in our understanding of how cancer cells repair DNA damage have
      made it possible to consider modification of the DNA damage response as a way in
      which resistance to radiotherapy and chemotherapy might be overcome. PARP
      inhibitors are potent but nontoxic drugs that inhibit repair of DNA single-strand
      breaks and increase the cytotoxic effects of radiotherapy and alkylating
      chemotherapy agents, including temozolomide. PARP inhibitors have potential
      applications in neuro-oncology because there is increasing evidence that their
      radio- and chemo-sensitizing effects are tumor specific. This review explores the
      mechanisms of action of PARP inhibitors and describes their putative mechanisms
      of radio- and chemo-sensitization in the context of CNS oncology. The authors go
      on to review their development in recent clinical trials, with a focus on
      glioblastoma.

PMID- 25054303
TI  - Shaping the glioma immune microenvironment through tryptophan metabolism.
AB  - The metabolism of the essential amino acid tryptophan is a key microenvironmental
      factor shaping the immunobiology of many tumor types. The current concept
      suggests that in the tumor microenvironment, tryptophan is metabolized by
      specialized dioxygenases, chiefly indoleamine-2,3-dioxygenase (IDO), which is
      expressed by tumor cells and antigen-presenting cells. High IDO activity leads to
      the depletion of tryptophan from the local microenvironment, while immediate
      tryptophan metabolites, particularly kynurenine, accumulate to high micromolar
      levels. Both the depletion of tryptophan and the accumulation of kynurenine lead
      to profound suppression of T-cell responses. Orally active IDO inhibitors are
      currently being explored in clinical trials for their efficacy in enhancing
      antitumor immune responses. Recent evidence points at alternative routes of
      tryptophan catabolism via tryptophan-2,3-dioxygenase, which is particularly
      expressed in malignant gliomas resulting in the production of high amounts of
      kynurenine. Tryptophan-2,3-dioxygenase-derived kynurenine in turn leads to the
      promotion of glioma growth and invasiveness and the suppression of antitumor
      immune responses by binding to the aryl hydrocarbon receptor expressed in glioma
      cells and glioma-infiltrating T cells. These new data open up novel therapeutic
      approaches to alleviate glioma-mediated immunosuppression. This review summarizes
      the current view on the relevance of tryptophan metabolism as an important
      immunosuppressive, proinvasive and growth-promoting metabolic pathway in
      malignant glioma.

PMID- 25054304
TI  - Comparison of between-training-sessions recovery strategies for world-class BMX
      pilots.
AB  - PURPOSE: To assess the impact of between-training-sessions recovery strategies
      (passive [PAS], active [ACT], cold-water immersion [CWI], and ingestion of a
      recovery drink [NUTR]) on maximal cycling performance, perceptions of delayed
      onset muscle soreness (DOMS), and fatigue in world-class BMX riders. METHODS:
      Eleven elite BMX athletes, members of the French national team (top country in
      the 2011 international ranking, 4 medals at the 2012 World Championships, top
      European country), participated in the study, which involved standardized
      training periods. Athletes performed 3 maximal-sprint power tests: the first day
      of the week before the training session and before and after training on the
      third day of the week (D3). The recovery strategy was randomly assigned to each
      participant on day 2 immediately after the last training period of the day.
      Perceptions of DOMS and general fatigue were recorded on D3. RESULTS: After
      training on D3, the decrease in maximal-sprint power (Pmax) was significantly
      greater for PAS than with CWI (P=.02) and NUTR (P=.018). Similar results were
      found with ACT (vs CWI P=.044, and vs NUTR P=.042). Self-reported DOMS and
      fatigue were significantly greater after PAS than after other strategies.
      CONCLUSIONS: For elite BMX riders, between training days, nutritional and/or CWI
      recovery strategies appear to be best for reducing muscle fatigue and increasing
      the capacity to withstand the training schedule.

PMID- 25054305
TI  - Discontinuity of human presence at Atapuerca during the early Middle Pleistocene:
      a matter of ecological competition?
AB  - Increasing evidence suggests that the European human settlement is older than 1.2
      Ma. However, there is a fierce debate about the continuity or discontinuity of
      the early human settlement of Europe. In particular, evidence of human presence
      in the interval 0.7-0.5 Ma is scarce in comparison with evidence for the previous
      and later periods. Here, we present a case study in which the environmental
      conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period
      without evidence of human presence, are compared with the conditions in the
      previous period, for which a relatively intense human occupation is documented.
      With this objective in mind, the available resources for a human population and
      the intensity of competition between secondary consumers during the two periods
      are compared using a mathematical model. The Gran Dolina site TD8 level, dated to
      0.7-0.6 Ma, is taken as representative of the period during which Atapuerca was
      apparently not occupied by humans. Conditions at TD8 are compared with those of
      the previous period, represented by the TD6-2 level, which has yielded abundant
      evidence of intense human occupation. The results show that survival
      opportunities for a hypothetical human population were lower at TD8 than they
      were at TD6-2. Increased resource competition between secondary consumers arises
      as a possible explanation for the absence of human occupation at Atapuerca in the
      early Middle Pleistocene. 

PMID- 25054306
TI  - Total synthesis of putative montamine and a proposed structural reassignment.
AB  - The natural product montamine was originally assigned as a homodimer of
      moschamine linked by a N-N' bond at the serotonin side-chain. A total synthesis
      of the reported structure has shown this to be incorrect. Analysis of the
      spectroscopic data suggests that the dimerization site has been incorrectly
      assigned, and montamine is likely to be a 4,4'-bismoschamine natural product
      previously described in the literature. 

PMID- 25054308
TI  - Are insulin analogues detemir or glulisine used preferentially in
      overweight/obese subjects? A German multicentre analysis of 38560 type 2 diabetic
      patients from the DPV registry.
AB  - OBJECTIVE: Several studies suggest benefits of insulin analogues detemir or
      glulisine in overweight and obese patients with type 2 diabetes. The present
      multicentre study therefore examines, whether these insulin analogues are used
      more frequently in patients with increased body mass index. METHODS: Data of 38
      560 adult type 2 diabetic patients using insulin analogues, from 150 centres in
      Germany, registered in a standardized, prospective, computer-based documentation
      program (DPV), were included. Patients were classified into body mass index
      categories according to World Health Organization. Analysis was stratified by 3
      time periods. To adjust for confounding effects, multivariable logistic
      regression models were created. RESULTS: Detemir was preferentially used in
      overweight (OR 1.36, 95%-CI 1.20-1.53) and obese patients (OR 2.06, 95%-CI 1.84
      2.31) compared to normal-weight patients. These effects remained significant
      after adjusting for sex, age, new/old federal state of Germany, size of centre,
      treatment in university clinic and clinic/specialized private practice. Models
      were additionally adjusted for time period and interaction of BMI category with
      age or sex. For glulisine, a minor effect was present when comparing obese to
      normal-weight patients (OR 1.26, 95%-CI 1.06-1.50). After adjustment, this
      finding was no longer significant. Stratified by obesity grade, class III obese
      patients more frequently used detemir or glulisine compared to class I obese
      patients. Comparing time periods, odds ratios did not differ, neither for detemir
      nor for glulisine. CONCLUSION:  Detemir is used more often in overweight and
      obese patients compared to normal-weight patients. For glulisine, the
      relationship is less pronounced.

PMID- 25054309
TI  - Serum adiponectin and progranulin levels are associated with gallstone disease.
AB  - BACKGROUND/AIM: Aberrant adipokine serum concentrations are associated with a
      variety of obesity-related diseases. This study was designed to investigate the
      putative role of the adipokines adiponectin, chemerin, progranulin, vaspin,
      fibroblast growth factor 21 (FGF21) and adipocyte fatty acid binding protein
      (AFABP) in gallstone disease. METHODS: Serum levels of adiponectin, chemerin,
      progranulin, vaspin, FGF21 and AFABP of 189 gallstone patients and 833 healthy
      controls were measured by enzyme-linked immunosorbent assays. RESULTS: Increased
      adiponectin levels were nominally associated with lower gallstone risk in women
      (p=0.036, odds ratio (OR) 0.47, 95% confidence interval (CI) [0.23; 0.95]).
      Furthermore progranulin serum concentrations in men were significantly elevated
      in gallstone carriers in comparison to controls (p=0.012, OR 6.1, 95% CI [1.5;
      24.9]). Serum levels of chemerin, vaspin, FGF21 and AFABP did not differ between
      controls and subjects with gallstones. CONCLUSION: Our data further support a
      protective effect of adiponectin on gallstone risk and suggest a role of
      progranulin in the pathophysiology of cholelithiasis. Nevertheless, longitudinal
      data and functional analyses would be required to assess the pathogenetic link
      between gallstone formation and adipokine serum levels.

PMID- 25054310
TI  - Safety results from OCAPI: a European Observational Cohort Study of insulin
      glulisine-treated children aged 6-12 years with type 1 diabetes.
AB  - OBJECTIVE: Data on the safety of insulin glulisine for type 1 diabetes are
      limited in paediatric populations. The European post-marketing Observational
      prospective Cohort study of children with type 1 diabetes treated with
      APIDRA((r)) (OCAPI) study evaluated the safety of insulin glulisine in children
      aged 6-12 years in real-life clinical practice, with a particular focus on the 6
      8 years age group. RESEARCH DESIGN AND METHODS: OCAPI was an international,
      multicentre, observational, non-interventional, prospective cohort study, in
      which 94 participants with type 1 diabetes (6-8 years age group: n=31; 9-12 years
      age group: n=63) received insulin glulisine for 6 months under normal, local
      conditions. The primary objective was the incidence of severe hypoglycaemia in
      all participants. RESULTS: Overall incidence of severe hypoglycaemia was 6.6
      events per 100 persons/year (7.2 and 6.3 events per 100 persons/year in the 6-8
      and 9-12 years age groups, respectively). 12 participants (all aged 9-12 years)
      experienced transient injection-site reactions. No systematic hypersensitivity
      reactions were reported. Only 1 participant (9-12 years age group) experienced a
      serious class-effect risk possibly related to insulin glulisine (severe
      hypoglycaemia requiring an Emergency Department visit). Glycated haemoglobin
      levels did not change markedly throughout the study, and were inversely
      proportional to the risk of hypoglycaemia. CONCLUSIONS: Insulin glulisine has a
      good safety profile in children with type 1 diabetes aged 6-12 years, with
      generally low rates of severe hypoglycaemia and few adverse reactions. These
      results are encouraging for its use in paediatric populations.

PMID- 25054311
TI  - The effect of metformin on androgen production in diabetic women with non-classic
      congenital adrenal hyperplasia.
AB  - Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common
      genetic disorders, is often associated with the clinical features of
      hyperandrogenism. This study included 19 women with recently diagnosed and
      previously untreated type 2 diabetes, 8 of whom suffered from NC-CAH, treated
      with metformin (2.55-3.0 g daily). Glucose homeostasis markers, plasma lipids, as
      well as plasma levels of 17-hydroxyprogesterone, androgens and gonadotropins were
      assessed at baseline and after 6 months of therapy. In both groups of patients,
      metformin reduced fasting plasma glucose, insulin resistance, triglycerides and
      glycated hemoglobin. Moreover, in patients with NC-CAH, but not in women with
      normal adrenal function, metformin decreased plasma levels of 17
      hydroxyprogesterone, total and free testosterone, androstenedione and
      dehydroepiandrosterone sulphate. The obtained results suggest that metformin
      partially normalizes androgen production in symptomatic patients with NC-CAH. 

PMID- 25054312
TI  - The effects of hypokalaemia on the hormone exocytosis in adenohypophysis and
      prolactinoma cell culture model systems.
AB  - The extracellular ion milieu determines the exocytosis mechanism that is coupled
      to spontaneous electrical activity. The K(+) ion plays crucial role in this
      mechanism: as the potassium current is associated with membrane hyperpolarization
      and hormone release through protein cascade activation. The primary aim of this
      study was to investigate the response mechanisms of normal adenohypophysis and
      adenohypophyseal prolactinoma cell populations at different extracellular K(+)
      levels with an otherwise isoionic milieu of all other essential ions. We focused
      on prolactin (PRL) and adrenocorticotrophic hormone (ACTH) release.In our
      experimental study, female Wistar rats (n=20) were treated with estrone-acetate
      (150 MUg/kg b.w./week) for 6 months to induce prolactinomas in the
      adenohypophysis. Primary, monolayer cell cultures were prepared by enzymatic and
      mechanical digestion. PRL and ACTH hormone presence was measured by
      radioimmunoassay or immuno-chemiluminescence assay. Immunocytochemistry was used
      to assess the apoptotic cells.Differences between the effects of hypokalaemia on
      normal adenohypophysis cultures and prolactinoma cell populations were
      investigated. Significant alteration (p<0.001, n=10) in hormone exocytosis was
      detected in K(+) treated adenohypophyseal and prolactinoma cell cultures compared
      to untreated groups. Immunocyto-chemistry showed that Bcl-2 expression was
      reduced under hypokalaemic conditions.The decrease in hormone exocytosis was
      tightly correlated to the extracellular K(+) in both cell types, leading to the
      conclusion that external K(+) may be the major factor for the inhibition of
      hormone release. The significant increase in hormone content in supernatant media
      suggests that hypokalaemia may play important role in apoptosis. 

PMID- 25054313
TI  - Sandbox University: estimating influence of institutional action.
AB  - The approach presented in this article represents a generalizable and adaptable
      methodology for identifying complex interactions in educational systems and for
      investigating how manipulation of these systems may affect educational outcomes
      of interest. Multilayer Minimum Spanning Tree and Monte-Carlo methods are used. A
      virtual Sandbox University is created in order to facilitate effective
      identification of successful and stable initiatives within higher education,
      which can affect students' credits and student retention - something that has
      been lacking up until now. The results highlight the importance of teacher
      feedback and teacher-student rapport, which is congruent with current educational
      findings, illustrating the methodology's potential to provide a new basis for
      further empirical studies of issues in higher education from a complex systems
      perspective. 

PMID- 25054315
TI  - Prospective study of colorectal enhanced recovery after surgery in a community
      hospital.
AB  - IMPORTANCE: Enhanced recovery after surgery (ERAS) colorectal programs have shown
      to be successful at reducing length of stay in many international and academic
      centers; however, their efficacy in a community hospital setting remains unclear.
      OBJECTIVE: To determine if favorable results could be reproduced in a community
      hospital setting using our ERAS program, which was developed using core ERAS
      guidelines with the goal of accelerated recovery while also addressing other
      important outcomes affecting patient experience and safety. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective study of ERAS program, a multidisciplinary effort
      involving anesthesia, preadmission staff, nursing, and surgery staff at a
      community hospital. The program was initiated in 2010 and was in full practice by
      2011. We assessed practice patterns and patient outcomes for all elective colon
      and rectal resection cases performed in 2009 (prior to ERAS implementation),
      2011, and 2012. MAIN OUTCOMES AND MEASURES: Laparoscopic approach, narcotic use,
      length of stay, 30-day readmission, ileus (defined as reinsertion of nasogastric
      tube), and intra-abdominal infection and association between colorectal cancer
      (CRC) diagnosis and these outcomes. RESULTS: From 2009 to 2012, the use of
      laparoscopy increased from 57.4% to 88.8% (P < .001). Length of stay decreased
      significantly (6.7 days vs 3.7 days, P < .001), without an increase in 30-day
      readmission rate (17.6% vs 12.5%, P = .49). Use of patient-controlled narcotic
      analgesia and duration of use decreased (63.2% of patients vs 15%, P < .001; 67.8
      hours vs 47.1 hours, P = .02). Ileus rate decreased from 13.2% to 2.5% (P = .02).
      Intra-abdominal infection decreased from 7.4% to 2.5% (P = .24). When comparing
      laparoscopic cases alone, similar results were observed. Following regression
      analysis, there were no statistically significant differences between CRC
      diagnosis and LOS, 30-day readmission rates, ileus, and intra-abdominal infection
      (all P's > .05). Length of stay reductions resulted in an estimated cost savings
      of $3202 per patient (2011) and $4803 per patient (2012). CONCLUSIONS AND
      RELEVANCE: Implementation of this patient care-directed enhanced recovery program
      is feasible in a community hospital setting, and it is associated with decreased
      LOS without increased readmission or morbidity, as well as significant decreases
      in narcotic use and cost. Improved outcomes are independent of the laparoscopic
      approach and CRC diagnosis.

PMID- 25054314
TI  - Kinetic Interpretation of the Importance of OATP1B3 and MRP2 in Docetaxel-Induced
      Hematopoietic Toxicity.
AB  - Neutropenia is a lethal dose-limiting toxicity of docetaxel. Our previous report
      indicated that the prevalence of severe docetaxel-induced neutropenia is
      significantly associated with genetic polymorphisms in solute carrier organic
      anion transporter 1B3 (SLCO1B3) (encoding organic anion-transporting polypeptide
      1B3 (OATP1B3)) and ATP-binding cassette subfamily C2 (ABCC2) (encoding multidrug
      resistant-associated protein 2 (MRP2)). Therefore, we investigated their
      significance in docetaxel-induced neutropenia. In vitro experiments suggested
      their possible involvement in the hepatic uptake of docetaxel and its efflux from
      bone marrow cells. To further characterize a quantitative impact of OATP1B3 and
      MRP2 on neutropenia, we used an in silico simulation of the neutrophil count in
      docetaxel-treated subjects with functional changes in OATP1B3 and MRP2 in a
      pharmacokinetic/pharmacodynamic model. The clinically reported odds ratios for
      docetaxel-induced neutropenia risk were explained by the decreased function of
      OATP1B3 and MRP2 to 41 and 32%, respectively. These results suggest that reduced
      activities of OATP1B3 and MRP2 associated with systemic exposure and local
      accumulation in bone marrow cells, respectively, account for the docetaxel
      induced neutropenia observed clinically. 

PMID- 25054316
TI  - Nanoparticles in drug delivery: mechanism of action, formulation and clinical
      application towards reduction in drug-associated nephrotoxicity.
AB  - INTRODUCTION: Over the past few decades, nanoparticles (NPs) have gained
      immeasurable interest in the field of drug delivery. Various NP formulations have
      been disseminated in drug development in an attempt to increase efficacy, safety
      and tolerability of incorporated drugs. In this context, NP formulations that
      increase solubility, control release, and/or affect the in vivo disposition of
      drugs, were developed to improve the pharmacokinetic and pharmacodynamic
      properties of encapsulated drugs. AREAS COVERED: In this article, important
      properties related to NP function such as particle size, surface charge and shape
      are disseminated. Also, the current understanding of how NP characteristics
      affect particle uptake and targeted delivery is elucidated. Selected NP systems
      currently used in delivery of drugs in biological systems and their production
      methods are discussed as well. Emphasis is placed on current NP formulations that
      are shown to reduce drug-induced adverse renal complications. EXPERT OPINION:
      Formulation designs utilizing NP-encapsulated drugs offer alternative
      pharmacotherapy options with improved safety profiles for current and emerging
      drugs. NPs have been shown to increase the therapeutic index of several entrapped
      drugs mostly by decreasing drug localization and side effects on organs. Recent
      studies on NP-encapsulated chemotherapeutic and antibiotic medications show
      enhanced therapeutic outcomes by altering drug degradation, increasing systemic
      circulation and/or enhancing cell specific targeting. They may also reduce the
      distribution of encapsulated drugs into the kidneys and attenuate drug-associated
      adverse renal complications. The usefulness of NP formulation in reducing the
      nephrotoxicity of nonsteroidal anti-inflammatory drugs is an under explored
      territory that deserves more attention.

PMID- 25054317
TI  - Anisotropic magnetic behavior of single crystalline CeTiGe3 and CeVGe3.
AB  - We have grown the single crystals of iso-structural CeTiGe3 and CeVGe3 compounds
      by using Ce-Ge eutectic as flux. Using the techniques of magnetization,
      electrical resistivity and heat capacity, our data on single crystals reveal
      pronounced magnetic anisotropies in these compounds with hexagonal symmetry. The
      c-axis is the easy axis of magnetization in CeTiGe3 which orders
      ferromagnetically at 14 K, and a gap in the magnon excitation spectra of ~ 28 K
      is inferred from both electrical resistivity and heat capacity. The electrical
      resistivity of CeTiGe3 shows anisotropic Kondo behavior and the heat capacity
      indicates the existence of the first excited crystal electric field split doublet
      lying at about ~ 50 K. The nature of magnetic ordering changes to
      antiferromagnetic in CeVGe3, which undergoes a magnetic transition at TN ~ 6 K
      with the a - b plane as the easy plane of magnetization. Below TN, the electrical
      resistivity of CeVGe3 along the c axis shows an upturn due to the opening of a
      gap. The 4f contribution to the resistivity rho4f establishes that CeVGe3, like
      the Ti analog, is also a Kondo lattice compound. The present work on single
      crystals further advances our understanding of these materials based on
      polycrystalline samples which have been studied earlier in the literature.

PMID- 25054318
TI  - Identifying the subfamilies of voltage-gated potassium channels using feature
      selection technique.
AB  - Voltage-gated K+ channel (VKC) plays important roles in biology procession,
      especially in nervous system. Different subfamilies of VKCs have different
      biological functions. Thus, knowing VKCs' subfamilies has become a meaningful job
      because it can guide the direction for the disease diagnosis and drug design.
      However, the traditional wet-experimental methods were costly and time-consuming.
      It is highly desirable to develop an effective and powerful computational tool
      for identifying different subfamilies of VKCs. In this study, a predictor, called
      iVKC-OTC, has been developed by incorporating the optimized tripeptide
      composition (OTC) generated by feature selection technique into the general form
      of pseudo-amino acid composition to identify six subfamilies of VKCs. One of the
      remarkable advantages of introducing the optimized tripeptide composition is
      being able to avoid the notorious dimension disaster or over fitting problems in
      statistical predictions. It was observed on a benchmark dataset, by using a
      jackknife test, that the overall accuracy achieved by iVKC-OTC reaches to 96.77%
      in identifying the six subfamilies of VKCs, indicating that the new predictor is
      promising or at least may become a complementary tool to the existing methods in
      this area. It has not escaped our notice that the optimized tripeptide
      composition can also be used to investigate other protein classification
      problems. 

PMID- 25054319
TI  - Molecular method for sex identification of half-smooth tongue sole (Cynoglossus
      semilaevis) using a novel sex-linked microsatellite marker.
AB  - Half-smooth tongue sole (Cynoglossus semilaevis) is one of the most important
      flatfish species for aquaculture in China. To produce a monosex population, we
      attempted to develop a marker-assisted sex control technique in this sexually
      size dimorphic fish. In this study, we identified a co-dominant sex-linked marker
      (i.e., CyseSLM) by screening genomic microsatellites and further developed a
      novel molecular method for sex identification in the tongue sole. CyseSLM has a
      sequence similarity of 73%-75% with stickleback, medaka, Fugu and Tetraodon. At
      this locus, two alleles (i.e., A244 and A234) were amplified from 119 tongue sole
      individuals with primer pairs CyseSLM-F1 and CyseSLM-R. Allele A244 was present
      in all individuals, while allele A234 (female-associated allele, FAA) was mostly
      present in females with exceptions in four male individuals. Compared with the
      sequence of A244, A234 has a 10-bp deletion and 28 SNPs. A specific primer
      (CyseSLM-F2) was then designed based on the A234 sequence, which amplified a 204
      bp fragment in all females and four males with primer CyseSLM-R. A time-efficient
      multiplex PCR program was developed using primers CyseSLM-F2, CyseSLM-R and the
      newly designed primer CyseSLM-F3. The multiplex PCR products with co-dominant
      pattern could be detected by agarose gel electrophoresis, which accurately
      identified the genetic sex of the tongue sole. Therefore, we have developed a
      rapid and reliable method for sex identification in tongue sole with a newly
      identified sex-linked microsatellite marker. 

PMID- 25054320
TI  - Astragalus membranaceus inhibits peritoneal fibrosis via monocyte chemoattractant
      protein (MCP)-1 and the transforming growth factor-beta1 (TGF-beta1) pathway in
      rats submitted to peritoneal dialysis.
AB  - Inflammation and transforming growth factor-beta1 (TGF-beta1) contribute to the
      development of peritoneal fibrosis (PF), which is associated with peritoneal
      dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and
      anti-fibrotic effects in many diseases. The goal of this study was to determine
      the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of
      PD was induced using standard PD fluid, and PF was verified by HE and Masson's
      staining, as well as through the expression of fibroblast surface protein (FSP)
      and collagen III. The expression levels of monocyte chemoattractant protein (MCP)
      1, F4/80 (macrophage/monocyte marker in rat), TGF-beta1 and the downstream
      proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without
      Astragalus was evaluated using immunohistochemistry analysis. Overall
      correlations between MCP-1 and TGF-beta1 staining were analyzed using both the
      Spearman and Pearson methods. The results showed that Astragalus could inhibit
      the recruitment and activation of monocytes/macrophages, thereby reducing the
      production of TGF-beta1 in the dialyzed peritoneal membrane. PF was also
      significantly decreased following treatment with Astragalus. MCP-1 expression had
      a strong positive correlation with TGF-beta1 sensitivity, suggesting that the
      anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-beta1
      pathway. Our results indicate that Astragalus could be a useful agent against PD
      induced PF. 

PMID- 25054322
TI  - Improved fibroblast functionalities by microporous pattern fabricated by
      microelectromechanical systems.
AB  - Fibroblasts, which play an important role in biological seal formation and
      maintenance, determine the long-term success of percutaneous implants. In this
      study, well-defined microporous structures with micropore diameters of 10-60 um
      were fabricated by microelectromechanical systems and their influence on the
      fibroblast functionalities was observed. The results show that the microporous
      structures with micropore diameters of 10-60 um did not influence the initial
      adherent fibroblast number; however, those with diameters of 40 and 50 um
      improved the spread, actin stress fiber organization, proliferation and
      fibronectin secretion of the fibroblasts. The microporous structures with
      micropore diameters of 40-50 um may be promising for application in the
      percutaneous part of an implant. 

PMID- 25054321
TI  - Molecular and cellular mechanisms of sperm-oocyte interactions opinions relative
      to in vitro fertilization (IVF).
AB  - One of the biggest prerequisites for pregnancy is the fertilization step, where a
      human haploid spermatozoon interacts and penetrates one haploid oocyte in order
      to produce the diploid zygote. Although fertilization is defined by the presence
      of two pronuclei and the extraction of the second polar body the process itself
      requires preparation of both gametes for fertilization to take place at a
      specific time. These preparations include a number of consecutive biochemical and
      molecular events with the help of specific molecules and with the consequential
      interaction between the two gametes. These events take place at three different
      levels and in a precise order, where the moving spermatozoon penetrates (a) the
      outer vestments of the oocyte, known as the cumulus cell layer; (b) the zona
      pellucida (ZP); where exocytosis of the acrosome contents take place and (c)
      direct interaction of the spermatozoon with the plasma membrane of the oocyte,
      which involves a firm adhesion of the head of the spermatozoon with the oocyte
      plasma membrane that culminates with the fusion of both sperm and oocyte
      membranes (Part I). After the above interactions, a cascade of molecular signal
      transductions is initiated which results in oocyte activation. Soon after the
      entry of the first spermatozoon into the oocyte and oocyte activation, the
      oocyte's coat (the ZP) and the oocyte's plasma membrane seem to change quickly in
      order to initiate a fast block to a second spermatozoon (Part II). Sometimes, two
      spermatozoa fuse with one oocyte, an incidence of 1%-2%, resulting in polyploid
      fetuses that account for up to 10%-20% of spontaneously aborted human
      conceptuses. The present review aims to focus on the first part of the human
      sperm and oocyte interactions, emphasizing the latest molecular and cellular
      mechanisms controlling this process. 

PMID- 25054323
TI  - Arginine enhances osteoblastogenesis and inhibits adipogenesis through the
      regulation of Wnt and NFATc signaling in human mesenchymal stem cells.
AB  - Arginine, an alpha-amino acid, has been reported to exert beneficial effects that
      ameliorate health problems and prevent excessive fat deposition. In this study,
      we investigated whether the activation of cell signaling by arginine can induce
      osteogenic differentiation and modulate excessive adipogenic differentiation in
      human mesenchymal stem cells (MSCs). Arginine potently induced the expression of
      type Ialpha1 collagen, osteocalcin, and ALP in a dose-dependent manner without
      causing cytotoxicity. Arginine significantly increased the mRNA expression of the
      osteogenic transcription factors runt-related transcription factor 2 (Runx2),
      DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by
      decreasing adipocyte formation and triglyceride (TG) content in MSCs and
      inhibiting the mRNA expression of the adipogenic transcription factors peroxisome
      proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer-binding protein
      alpha (C/EBPalpha), and fatty acid binding protein 4 (Fabp4). This effect was
      associated with increased expression of Wnt5a, and nuclear factor of activated T
      cells (NFATc), and was abrogated by antagonists of Wnt and NFATc, which indicated
      a role of Wnt and NFATc signaling in the switch from adipogenesis to
      osteoblastogenesis induced by arginine. In conclusion, this is the first report
      of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte
      formation through involving Wnt5a and NFATc signaling pathway. 

PMID- 25054324
TI  - The challenge of living on: psychopathology and its mediating influence on the
      readjustment of former child soldiers.
AB  - Current civil wars are characterized by the increasing involvement of civilian
      populations and the systematic employment of child soldiers. An example of such
      wars was the conflict in Northern Uganda, where the war-affected population is
      still challenged by the reintegration of formerly abducted children and youths. A
      cross-sectional, population-based survey, using a multistage cluster sampling
      approach of 1,113 Northern Ugandans aged between 12 and 25 in camps for
      internally displaced persons and locally validated instruments was conducted to
      assess symptoms and diagnoses of Posttraumatic Stress Disorder (PTSD) and
      probable Depression in war-affected, as well as formerly abducted individuals.
      Further objectives were to determine predictors of psychopathology and to relate
      indicators of maladjustment (i.e., impairments in daily and community
      functioning, somatic complaints, suicidality, aggressiveness and discrimination)
      to abduction, level of exposure to violence and psychopathology. 43% of the
      sample reported abduction by the rebel army. Exposure to violence among this
      group was higher than for non-abducted youths (t = 28.05; p<.001). PTSD point
      prevalence rates were 25% among former child soldiers and 7% among the comparison
      group. High suicidal ideation was present in 16% and 6% respectively. A higher
      amount of experienced and witnessed event-types (beta = . 32. p<.001), loss of
      first-degree relatives (beta = .13. p<.001) and the number of event-types
      involving forced perpetration (beta = .23. p<.001) were identified as risk
      factors of PTSD symptoms in former child soldiers. The associations between
      abductee-status and indicators of maladjustment were fully mediated by level of
      trauma exposure and psychopathology. Results show that child soldiering and its
      psychological sequelae affect a substantial proportion of children and youths.
      After release or flight, their readjustment depends at least partly on their
      level of mental traumatization. 

PMID- 25054325
TI  - The role of habitat complexity in community development is mediated by resource
      availability.
AB  - Habitat complexity strongly affects the structure and dynamics of ecological
      communities, with increased complexity often leading to greater species diversity
      and abundance. However, habitat complexity changes as communities develop, and
      some species alter their environment to themselves provide habitat for other
      species. Most experimental studies manipulate basal substrate complexity, and
      while the importance of complexity likely changes during community development,
      few studies have examined the temporal dynamics of this variable. We used two
      experiments to quantify the importance of basal substrate complexity to sessile
      marine invertebrate community development through space and time. First, we
      compared effects of substrate complexity at 70 sites across ten estuaries. Sites
      differed in recruitment and community development rates, and after three months
      provided spatial variation in community development stage. Second, we tested for
      effects of substrate complexity at multiple times at a single site. In both
      experiments, complexity affected marine sessile invertebrate community
      composition in the early stages of community development when resource
      availability was high. Effects of complexity diminished through time as the
      amount of available space (the primary limiting resource) declined. Our work
      suggests the presence of a bare-space threshold, at which structural complexity
      of the basal substrate is overwhelmed by secondary biotic complexity. This
      threshold will be met at different times depending on local recruitment and
      growth rates and is likely to vary with productivity gradients. 

PMID- 25054326
TI  - The effects of urban warming on herbivore abundance and street tree condition.
AB  - Trees are essential to urban habitats because they provide services that benefit
      the environment and improve human health. Unfortunately, urban trees often have
      more herbivorous insect pests than rural trees but the mechanisms and
      consequences of these infestations are not well documented. Here, we examine how
      temperature affects the abundance of a scale insect, Melanaspis tenebricosa
      (Comstock) (Hemiptera: Diaspididae), on one of the most commonly planted street
      trees in the eastern U.S. Next, we examine how both pest abundance and
      temperature are associated with water stress, growth, and condition of 26 urban
      street trees. Although trees in the warmest urban sites grew the most, they were
      more water stressed and in worse condition than trees in cooler sites. Our
      analyses indicate that visible declines in tree condition were best explained by
      scale-insect infestation rather than temperature. To test the broader relevance
      of these results, we extend our analysis to a database of more than 2700 Raleigh,
      US street trees. Plotting these trees on a Landsat thermal image of Raleigh, we
      found that warmer sites had over 70% more trees in poor condition than those in
      cooler sites. Our results support previous studies linking warmer urban habitats
      to greater pest abundance and extend this association to show its effect on
      street tree condition. Our results suggest that street tree condition and
      ecosystem services may decline as urban expansion and global warming exacerbate
      the urban heat island effect. Although our non-probability sampling method limits
      our scope of inference, our results present a gloomy outlook for urban forests
      and emphasize the need for management tools. Existing urban tree inventories and
      thermal maps could be used to identify species that would be most suitable for
      urban conditions. 

PMID- 25054327
TI  - Cellular localization and associations of the major lipolytic proteins in human
      skeletal muscle at rest and during exercise.
AB  - Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol
      and is increased during energy stress such as exercise. Adipose triglyceride
      lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin
      (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle
      lipolysis. Hence, we hypothesized that non-genomic regulation such as cellular
      localization and the interaction of these key proteins modulate muscle lipolysis
      during exercise. PLIN5, ATGL and CGI-58 were highly (>60%) colocated with Oil Red
      O (ORO) stained lipid droplets. PLIN5 was significantly colocated with ATGL,
      mitochondria and CGI-58, indicating a close association between the key lipolytic
      effectors in resting skeletal muscle. The colocation of the lipolytic proteins,
      their independent association with ORO and the PLIN5/ORO colocation were not
      altered after 60 min of moderate intensity exercise. Further experiments in
      cultured human myocytes showed that PLIN5 colocation with ORO or mitochondria is
      unaffected by pharmacological activation of lipolytic pathways. Together, these
      data suggest that the major lipolytic proteins are highly expressed at the lipid
      droplet and colocate in resting skeletal muscle, that their localization and
      interactions appear to remain unchanged during prolonged exercise, and,
      accordingly, that other post-translational mechanisms are likely regulators of
      skeletal muscle lipolysis.

PMID- 25054328
TI  - A 'terror of tyrannosaurs': the first trackways of tyrannosaurids and evidence of
      gregariousness and pathology in Tyrannosauridae.
AB  - The skeletal record of tyrannosaurids is well-documented, whereas their footprint
      record is surprisingly sparse. There are only a few isolated footprints
      attributed to tyrannosaurids and, hitherto, no reported trackways. We report the
      world's first trackways attributable to tyrannosaurids, and describe a new
      ichnotaxon attributable to tyrannosaurids. These trackways are from the Upper
      Cretaceous (Campanian - Maastrichtian) of northeastern British Columbia, Canada.
      One trackway consists of three tridactyl footprints, and two adjacent trackways
      consist of two footprints each. All three trackways show animals bearing
      southeast within an 8.5 meter-wide corridor. Similarities in depth and
      preservation of the tyrannosaurid tracks indicate that these three trackways were
      made by track-makers walking concurrently in the same direction. These trackways
      add significantly to previous osteology-based hypotheses of locomotion and
      behavior in Tyrannosauridae by providing ichnologic support for gregariousness in
      tyrannosaurids, and the first record of the walking gait of tyrannosaurids.

PMID- 25054329
TI  - The southern megalopolis: using the past to predict the future of urban sprawl in
      the Southeast U.S.
AB  - The future health of ecosystems is arguably as dependent on urban sprawl as it is
      on human-caused climatic warming. Urban sprawl strongly impacts the urban
      ecosystems it creates and the natural and agro-ecosystems that it displaces and
      fragments. Here, we project urban sprawl changes for the next 50 years for the
      fast-growing Southeast U.S. Previous studies have focused on modeling population
      density, but the urban extent is arguably as important as population density per
      se in terms of its ecological and conservation impacts. We develop simulations
      using the SLEUTH urban growth model that complement population-driven models but
      focus on spatial pattern and extent. To better capture the reach of low-density
      suburban development, we extend the capabilities of SLEUTH by incorporating
      street-network information. Our simulations point to a future in which the extent
      of urbanization in the Southeast is projected to increase by 101% to 192%. Our
      results highlight areas where ecosystem fragmentation is likely, and serve as a
      benchmark to explore the challenging tradeoffs between ecosystem health, economic
      growth and cultural desires. 

PMID- 25054330
TI  - Lineage-specific regulation of epigenetic modifier genes in human liver and
      brain.
AB  - Despite an abundance of studies on chromatin states and dynamics, there is an
      astonishing dearth of information on the expression of genes responsible for
      regulating histone and DNA modifications. We used here a set of 156 defined
      epigenetic modifier genes (EMG) and profiled their expression pattern in cells of
      different lineages. As reference value, expression data from human embryonic stem
      cells (hESC) were used. Hepatocyte-like cells were generated from hESC, and their
      EMG expression was compared to primary human liver cells. In parallel, we
      generated postmitotic human neurons (Lu d6), and compared their relative EMG
      expression to human cortex (Ctx). Clustering analysis of all cell types showed
      that neuronal lineage samples grouped together (94 similarly regulated EMG), as
      did liver cells (61 similarly-regulated), while the two lineages were clearly
      distinct. The general classification was followed by detailed comparison of the
      major EMG groups; genes that were higher expressed in differentiated cells than
      in hESC included the acetyltransferase KAT2B and the methyltransferase SETD7.
      Neuro-specific EMGs were the histone deacetylases HDAC5 and HDAC7, and the
      arginine-methyltransferase PRMT8. Comparison of young (Lu d6) and more aged (Ctx)
      neuronal samples suggested a maturation-dependent switch in the expression of
      functionally homologous proteins. For instance, the ratio of the histone H3 K27
      methyltransfereases, EZH1 to EZH2, was high in Ctx and low in Lu d6. The same was
      observed for the polycomb repressive complex 1 (PRC1) subunits CBX7 and CBX8. A
      large proportion of EMGs in differentiated cells was very differently expressed
      than in hESC, and absolute levels were significantly higher in neuronal samples
      than in hepatic cells. Thus, there seem to be distinct qualitative and
      quantitative differences in EMG expression between cell lineages. 

PMID- 25054331
TI  - Transcriptome analysis of the mud crab (Scylla paramamosain) by 454 deep
      sequencing: assembly, annotation, and marker discovery.
AB  - In this study, we reported the characterization of the first transcriptome of the
      mud crab (Scylla paramamosain). Pooled cDNAs of four tissue types from twelve
      wild individuals were sequenced using the Roche 454 FLX platform. Analysis
      performed included de novo assembly of transcriptome sequences, functional
      annotation, and molecular marker discovery. A total of 1,314,101 high quality
      reads with an average length of 411 bp were generated by 454 sequencing on a
      mixed cDNA library. De novo assembly of these 1,314,101 reads produced 76,778
      contigs (consisting of 818,154 reads) with 5.4-fold average sequencing coverage.
      The remaining 495,947 reads were singletons. A total of 78,268 unigenes were
      identified based on sequence similarity with known proteins (E<=0.00001) in
      UniProt and non-redundant protein databases. Meanwhile, 44,433 sequences were
      identified (E<=0.00001) using a BLASTN search against the NCBI nucleotide
      database. Gene Ontology (GO) analysis indicated that biosynthetic process, cell
      part, and ion binding were the most abundant terms in biological process,
      cellular component, and molecular function categories, respectively. Kyoto
      Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed that 4,878
      unigenes distributed in 281 different pathways. In addition, 19,011
      microsatellites and 37,063 potential single nucleotide polymorphisms were
      detected from the transcriptome of S. paramamosain. Finally, thirty polymorphic
      microsatellite markers were developed and used to assess genetic diversity of a
      wild population of S. paramamosain. So far, existing sequence resources for S.
      paramamosain are extremely limited. The present study provides a characterization
      of transcriptome from multiple tissues and individuals, as well as an assessment
      of genetic diversity of a wild population. These sequence resources will
      facilitate the investigation of population genetic diversity, the development of
      genetic maps, and the conduct of molecular marker-assisted breeding in S.
      paramamosain and related crab species. 

PMID- 25054332
TI  - Vibrio cholerae utilizes direct sRNA regulation in expression of a biofilm matrix
      protein.
AB  - Vibrio cholerae biofilms contain exopolysaccharide and three matrix proteins
      RbmA, RbmC and Bap1. While much is known about exopolysaccharide regulation,
      little is known about the mechanisms by which the matrix protein components of
      biofilms are regulated. VrrA is a conserved, 140-nt sRNA of V. cholerae, whose
      expression is controlled by sigma factor sigmaE. In this study, we demonstrate
      that VrrA negatively regulates rbmC translation by pairing to the 5' untranslated
      region of the rbmC transcript and that this regulation is not stringently
      dependent on the RNA chaperone protein Hfq. These results point to VrrA as a
      molecular link between the sigmaE-regulon and biofilm formation in V. cholerae.
      In addition, VrrA represents the first example of direct regulation of sRNA on
      biofilm matrix component, by-passing global master regulators. 

PMID- 25054336
TI  - Colonic phenotype of the ileum in Crohn's disease: a prospective study before and
      after ileocolonic resection.
AB  - BACKGROUND: Colonic metaplasia has been described in pouchitis. In a prospective
      study, we investigated whether colonic phenotype may develop in Crohn's disease
      (CD) ileum. The expression of sulfomucins (colonic mucin), sialomucins, and CD10
      (small intestine mucin and phenotype) was evaluated before and after ileocolonic
      resection for CD. METHODS: From February 2007 to March 2010, 22 patients with CD
      undergoing surgery were enrolled. Clinical (Crohn's Disease Activity Index >150)
      and endoscopic recurrence (Rutgeerts score >=1) rates were assessed at 6 and 12
      months. Ileal samples were taken at surgery (T0), at 6 (T1), and 12 months (T2)
      for histology, histochemistry (High Iron Diamine-Alcian Blue), and
      immunohistochemistry (anti-CD10). RESULTS: In 22 patients, recurrence was
      assessed at 6 and 12 months (clinical recurrence 9% and 18%; endoscopic
      recurrence 73% and 77%). In all 22 patients, ileal samples were taken at 6 and 12
      months (involved area in patients with recurrence). In 19 of 22 (86.3%) patients,
      the involved ileum was also studied at surgery. At T0, T1, and T2, the expression
      of sialomucins and CD10 (small intestine mucin and phenotype) was comparable and
      higher (P < 0.0001) than the expression of sulfomucins (colonic mucin) (mean
      [range], T0:82 [35-100] versus 75 [0-100] versus 16 [0-50]; T1:96 [60-100] versus
      94.7 [50-100] versus 3.89 [0-40]; T2:93.3 [60-100] versus 88.1 [25-100] versus
      6.6 [0-40]). The expression of small-intestine mucin and phenotype was higher at
      T1 (P = 0.025) versus T0 (P = 0.026). Differently, the expression of colonic
      mucin was lower at T1 versus T0 (P = 0.027). CONCLUSIONS: In CD, the ileum
      involved by severe/established lesions develops a "metaplastic" colonic mucosa
      phenotype. Differently, CD ileum with no lesions or with early recurrence
      maintains the "native" small intestine type mucin secretion and phenotype.

PMID- 25054335
TI  - Electrophysiological and structural remodeling in heart failure modulate
      arrhythmogenesis. 2D simulation study.
AB  - BACKGROUND: Heart failure is operationally defined as the inability of the heart
      to maintain blood flow to meet the needs of the body and it is the final common
      pathway of various cardiac pathologies. Electrophysiological remodeling,
      intercellular uncoupling and a pro-fibrotic response have been identified as
      major arrhythmogenic factors in heart failure. OBJECTIVE: In this study we
      investigate vulnerability to reentry under heart failure conditions by
      incorporating established electrophysiological and anatomical remodeling using
      computer simulations. METHODS: The electrical activity of human transmural
      ventricular tissue (5 cm * 5 cm) was simulated using the human ventricular action
      potential model Grandi et al. under control and heart failure conditions. The
      MacCannell et al. model was used to model fibroblast electrical activity, and
      their electrotonic interactions with myocytes. Selected degrees of diffuse
      fibrosis and variations in intercellular coupling were considered and the
      vulnerable window (VW) for reentry was evaluated following cross-field
      stimulation. RESULTS: No reentry was observed in normal conditions or in the
      presence of HF ionic remodeling. However, defined amount of fibrosis and/or
      cellular uncoupling were sufficient to elicit reentrant activity. Under
      conditions where reentry was generated, HF electrophysiological remodeling did
      not alter the width of the VW. However, intermediate fibrosis and cellular
      uncoupling significantly widened the VW. In addition, biphasic behavior was
      observed, as very high fibrotic content or very low tissue conductivity hampered
      the development of reentry. Detailed phase analysis of reentry dynamics revealed
      an increase of phase singularities with progressive fibrotic components.
      CONCLUSION: Structural remodeling is a key factor in the genesis of vulnerability
      to reentry. A range of intermediate levels of fibrosis and intercellular
      uncoupling can combine to favor reentrant activity.

PMID- 25054337
TI  - The impact of moderate-to-severe Crohn's Disease on employees' salary growth.
AB  - BACKGROUND: Moderate-to-severe Crohn's Disease (CD) has been shown to reduce
      daily activities; however, little is known of the impact on employees' salary
      growth. METHODS: Employment and health care benefit data were extracted from the
      OptumHealth Reporting and Insights database, aggregating data from 23 self
      insured U.S. companies with approximately 2.5 million covered beneficiaries.
      Employees diagnosed with moderate-to-severe CD (i.e., >=1 prescription fill for
      systemic corticosteroids, immunosuppressive drugs, methotrexate or cyclosporine,
      or biologic agents within 6 months after the first observed CD diagnosis) between
      January 1999 and December 2006 were retrospectively matched with controls without
      CD based on year of birth, sex, industry, and geographic region. Employees'
      salaries and salary growth rates were estimated and compared between cohorts.
      Both descriptive comparison and multivariate regression analyses controlling for
      baseline characteristics and differences in comorbidities were performed.
      RESULTS: A total of 918 employees with moderate-to-severe CD were matched to 2154
      CD-free controls. The 2 cohorts did not differ in their annual salary in the
      first year of observation. However, regression analyses revealed that the 2
      groups had significantly different adjusted annualized salary growth rates (0.69%
      versus 1.01%, P < 0.001), and employees with CD had a 31% lower salary increase
      rate than controls. A total income loss of $3195 per person was estimated for
      employees with CD compared with their CD-free peers over a cumulative 5 years
      after the first calendar year. CONCLUSIONS: In the United States, employees with
      moderate-to-severe CD had a substantially lower salary growth rate than their
      peers without CD, suggesting an impaired career progression.

PMID- 25054338
TI  - Magnetic resonance enterography in the evaluation of Crohn's disease: a primer
      for the gastroenterologist.
AB  - The assessment of disease location, severity, and complications is critical in
      guiding the choice of Crohn's disease therapy. Cross-sectional imaging studies
      have therefore had a paramount role in accurately staging Crohn's disease.
      Traditionally, computed tomography was the test of choice in confirming/excluding
      strictures, fistulae, and abscesses. Magnetic resonance imaging is now replacing
      computed tomography because it eliminates radiation risks. This review provides a
      primer for the gastroenterologist on magnetic resonance enterography in Crohn's
      disease.

PMID- 25054339
TI  - Research on psychiatric disorders targets inflammation.

PMID- 25054340
TI  - Towards a network of locally managed marine areas (LMMAs) in the Western Indian
      Ocean.
AB  - In the Western Indian Ocean (WIO), local communities are increasingly assuming
      responsibility for inshore marine resources either on their own or through
      collaborative management arrangements with governments or non-state actors. In
      this paper, we trace the evolution and expansion of community management in the
      WIO and present the first ever inventory and assessment of the region's locally
      managed marine areas (LMMAs). We compare the key attributes of these areas to
      those under government stewardship and assess their relative contributions to
      progress towards the Convention on Biodiversity (CBD) target of 10% of marine and
      coastal ecological regions to be effectively conserved by 2020. We also explore
      the legal frameworks that underpin locally managed marine initiatives in Kenya,
      Madagascar, Mozambique and Tanzania to assess the potential for future expansion.
      A principal finding is that whilst LMMAs protect more than 11,000 square
      kilometres of marine resource in the WIO, they are hampered by underdeveloped
      local and national legal structures and enforcement mechanisms. In our
      recommendations to improve local management, we suggest establishing a network of
      LMMA practitioners in the WIO region to share experiences and best practice. 

PMID- 25054341
TI  - Raised middle-finger: electrocortical correlates of social conditioning with
      nonverbal affective gestures.
AB  - Humans form impressions of others by associating persons (faces) with negative or
      positive social outcomes. This learning process has been referred to as social
      conditioning. In everyday life, affective nonverbal gestures may constitute
      important social signals cueing threat or safety, which therefore may support
      aforementioned learning processes. In conventional aversive conditioning, studies
      using electroencephalography to investigate visuocortical processing of visual
      stimuli paired with danger cues such as aversive noise have demonstrated
      facilitated processing and enhanced sensory gain in visual cortex. The present
      study aimed at extending this line of research to the field of social
      conditioning by pairing neutral face stimuli with affective nonverbal gestures.
      To this end, electro-cortical processing of faces serving as different
      conditioned stimuli was investigated in a differential social conditioning
      paradigm. Behavioral ratings and visually evoked steady-state potentials (ssVEP)
      were recorded in twenty healthy human participants, who underwent a differential
      conditioning procedure in which three neutral faces were paired with pictures of
      negative (raised middle finger), neutral (pointing), or positive (thumbs-up)
      gestures. As expected, faces associated with the aversive hand gesture (raised
      middle finger) elicited larger ssVEP amplitudes during conditioning. Moreover,
      theses faces were rated as to be more arousing and unpleasant. These results
      suggest that cortical engagement in response to faces aversively conditioned with
      nonverbal gestures is facilitated in order to establish persistent vigilance for
      social threat-related cues. This form of social conditioning allows to establish
      a predictive relationship between social stimuli and motivationally relevant
      outcomes. 

PMID- 25054342
TI  - The cation diffusion facilitator protein EmfA of Rhizobium etli belongs to a
      novel subfamily of Mn(2+)/Fe(2+) transporters conserved in alpha-proteobacteria.
AB  - Manganese (Mn(2+)) plays a key role in important cellular functions such as
      oxidative stress response and bacterial virulence. The mechanisms of Mn(2+)
      homeostasis are not fully understood, there are few data regarding the functional
      and taxonomic diversity of Mn(2+) exporters. Our recent phylogeny of the cation
      diffusion facilitator (CDF) family of transporters classified the bacterial
      Mn(2+)-CDF transporters characterized to date, Streptococcus pneumoniae MntE and
      Deinococcus radiodurans DR1236, into two monophyletic groups. DR1236 was shown to
      belong to the highly-diverse metal specificity clade VI, together with TtCzrB, a
      Zn(2+)/Cd(2+) transporter from Thermus thermophilus, the Fe(2+) transporter
      Sll1263 from Synechocystis sp and eight uncharacterized homologs whose potential
      Mn(2+)/Zn(2+)/Cd(2+)/Fe(2+) specificities could not be accurately inferred
      because only eleven proteins were grouped in this clade. A new phylogeny inferred
      from the alignment of 197 clade VI homologs revealed three novel subfamilies of
      uncharacterized proteins. Remarkably, one of them contained 91 uncharacterized
      alpha-proteobacteria transporters (46% of the protein data set) grouped into a
      single subfamily. The Mn(2+)/Fe(2+) specificity of this subfamily was proposed
      through the functional characterization of the Rhizobium etli RHE_CH03072 gene.
      This gene was upregulated by Mn(2+), Zn(2+), Cd(2+) and Fe(2+) but conferred only
      Mn(2+) resistance to R. etli. The expression of the RHE_CH03072 gene in an E.
      coli mntP/zitB/zntA mutant did not relieve either Zn(2+) or Mn(2+) stress but
      slightly increased its Fe(2+) resistance. These results indicate that the
      RHE_CH03072 gene, now designated as emfA, encodes for a bacterial Mn(2+)/Fe(2+)
      resistance CDF protein, having orthologs in more than 60 alpha-proteobacterial
      species. 

PMID- 25054343
TI  - Comparative potential of juvenile and adult human articular chondrocytes for
      cartilage tissue formation in three-dimensional biomimetic hydrogels.
AB  - Regeneration of human articular cartilage is inherently limited and extensive
      efforts have focused on engineering the cartilage tissue. Various cellular
      sources have been studied for cartilage tissue engineering including adult
      chondrocytes, and embryonic or adult stem cells. Juvenile chondrocytes (from
      donors below 13 years of age) have recently been reported to be a promising cell
      source for cartilage regeneration. Previous studies have compared the potential
      of adult and juvenile chondrocytes or adult and osteoarthritic (OA) chondrocytes.
      To comprehensively characterize the comparative potential of young, old, and
      diseased chondrocytes, here we examined cartilage formation by juvenile, adult,
      and OA chondrocytes in three-dimensional (3D) biomimetic hydrogels composed of
      poly(ethylene glycol) and chondroitin sulfate. All three human articular
      chondrocytes were encapsulated in the 3D biomimetic hydrogels and cultured for 3
      or 6 weeks to allow maturation and extracellular matrix formation. Outcomes were
      analyzed using quantitative gene expression, immunofluorescence staining,
      biochemical assays, and mechanical testing. After 3 and 6 weeks, juvenile
      chondrocytes showed a greater upregulation of chondrogenic gene expression than
      adult chondrocytes, while OA chondrocytes showed a downregulation. Aggrecan and
      type II collagen deposition and glycosaminoglycan accumulation were high for
      juvenile and adult chondrocytes but not for OA chondrocytes. Similar trend was
      observed in the compressive moduli of the cartilage constructs generated by the
      three different chondrocytes. In conclusion, the juvenile, adult and OA
      chondrocytes showed differential responses in the 3D biomimetic hydrogels. The 3D
      culture model described here may also provide a useful tool to further study the
      molecular differences among chondrocytes from different stages, which can help
      elucidate the mechanisms for age-related decline in the intrinsic capacity for
      cartilage repair. 

PMID- 25054345
TI  - Reply: To PMID 23719402.

PMID- 25054344
TI  - Bone marrow mesenchymal stem cells enhance bone formation in orthodontically
      expanded maxillae in rats.
AB  - OBJECTIVE: To transplant bone marrow-derived mesenchymal stem cells (MSCs) into
      the interpremaxillary suture after rapid maxillary expansion with the aim of
      increasing new bone formation in the suture. MATERIALS AND METHODS: Nineteen male
      Wistar rats were divided into two groups (control, n  =  9; experimental, n  = 
      10). Both groups were subjected to expansion for 5 days, and 50 cN of force was
      applied to the maxillary incisors with a helical spring. Pkh67(+) (green
      fluorescent dye)-labeled MSCs were applied to the interpremaxillary suture after
      force application into the interpremaxillary suture of rats. Bone formation in
      the sutural area was histomorphometrically evaluated, including the amount of new
      bone formation (um(2)), number of osteoblasts, number of osteoclasts, and number
      of vessels. Mann-Whitney U-test was used for statistical evaluation at the P <
      .05 level. RESULTS: After 10 days of retention, Pkh67(+) can be detected in
      suture mostly in the injection site under fluorescence microscope.
      Histomorphometric analysis revealed that a single local injection of MSCs into
      the midpalatal suture increased the new bone formation in the suture by
      increasing the number of osteoblasts and new vessel formation, compared with
      controls injected with phosphate-buffered saline. CONCLUSIONS: This preclinical
      study might provide foundations for the underlying potential clinical use of MSCs
      after maxillary expansion. Given the fact that MSCs are currently in use in
      clinical trials, this approach might be a feasible treatment strategy to
      accelerate new bone tissue formation in midpalatal suture and to shorten the
      treatment period for patients undergoing maxillary expansion reinforcement.

PMID- 25054346
TI  - Reply: To PMID 23881225.

PMID- 25054347
TI  - The effects of scapular mobilization in patients with subacromial impingement
      syndrome: a randomized, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To determine the effects of scapular mobilization on function, pain,
      range of motion, and satisfaction in patients with subacromial impingement
      syndrome (SAIS). DESIGN: Randomized, double-blind, placebo-controlled clinical
      trial. SETTING: University hospital clinics in Turkey. PARTICIPANTS: 66
      participants (mean +/- SD age 52.06 +/- 3.71 y) with SAIS. INTERVENTIONS:
      Participants were randomized into 3 groups: scapular mobilization, sham scapular
      mobilization, and supervised exercise. Before the interventions transcutaneous
      electrical stimulation and hot pack were applied to all groups. Total
      intervention duration for all groups was 3 wk with a total of 9 treatment
      sessions. MAIN OUTCOME MEASURES: Shoulder function and pain intensity were
      primary outcome measures; range of motion and participant satisfaction were
      secondary outcome measures. Shoulder function was assessed with the short form of
      the Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH). A visual
      analog scale was used to evaluate pain severity. Active range of motion was
      measured with a universal goniometer. A 7-point Likert scale was used to evaluate
      satisfaction. Outcome measurements were performed at baseline, before visits 5
      and 10, 4 wk after visit 9, and 8 wk after visit 9. RESULTS: There was no group
      difference for DASH score (P = .75), pain at rest (P = .41), pain with activity
      (P = .45), pain at night (P = .74), and shoulder flexion (P = .65), external
      rotation (P = .63), and internal rotation (P = .19). There was a significant
      increase in shoulder motion and function and a significant decrease in pain
      across time when all groups were combined (P < .001). The level of satisfaction
      was not significantly different for any of the questions about participant
      satisfaction between all groups (P > .05). CONCLUSION: There was not a
      significant advantage of scapular mobilization for shoulder function, pain, range
      of motion, and satisfaction compared with sham or supervised-exercise groups in
      patients with SAIS.

PMID- 25054348
TI  - MTHFR C677T predisposes to POAG but not to PACG in a North Indian population: a
      case control study.
AB  - Hyperhomocysteinemia induced by the C677T genetic variant in MTHFR
      (methylenetetrahydrofolate reductase) has been implicated in neuronal cell death
      of retinal ganglion cells (RGC), which is a characteristic feature of glaucoma.
      However, association of MTHFR C677T with glaucoma has been controversial because
      of inconsistent results across association studies. Association between MTHFR
      C677T and glaucoma has not been reported in Indian population. Therefore, with a
      focus on neurodegenerative death of RGC in glaucoma, the current study aimed to
      investigate association of MTHFR C677T with Primary Open Angle Glaucoma (POAG)
      and Primary Angle Closure Glaucoma (PACG) in a North Indian population. A total
      of 404 participants (231 patients and 173 controls) were included in this study.
      Genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length
      Polymorphism. A few random samples were also tested by direct sequencing.
      Genotypic and allelic distributions of the POAG and PACG cohorts were compared to
      that of controls by chi-square test and odds ratios were reported with 95%
      confidence intervals. Genotypic and allelic distributions between POAG cases and
      controls were significantly different (p = 0.03 and p = 0.01 respectively).
      Unlike POAG, we did not find significant difference in the genotypic and allelic
      distributions of C677T between PACG cases and controls (p>0.05). We also observed
      a higher proportion of TT associated POAG in females than that in males. However,
      this is a preliminary indication of gender specific risk of C677T that needs to
      be replicated in a larger cohort of males and females. The present investigation
      on MTHFR C677T and glaucoma reveals that the TT genotype and T allele of this
      polymorphism are significant risk factors for POAG but not for PACG in North
      Indian population. Ours is the first report demonstrating association of MTHFR
      C677T with POAG but not PACG in individuals from North India.

PMID- 25054350
TI  - Is there effective systemic therapy for recurrent surgery- and radiation
      refractory meningioma?

PMID- 25054353
TI  - Ask the experts: Maintaining neurological function in brain tumor resection.

PMID- 25054354
TI  - Interview: Current state of brain and spine radiosurgery and future applications.

PMID- 25054356
TI  - Conference scene: Neuro-oncology insights from European Society of Medical
      Oncology 2012.
AB  - European Society of Medical Oncology (ESMO), the annual conference of the ESMO,
      has become one of the leading oncological meetings worldwide. This year's ESMO
      was held in Vienna, Austria, from 28 September to 2 October, attracted more than
      16,000 attendees from around the world and was dedicated to the implementation of
      personalized medicine in all oncologic subdisciplines, including neuro-oncology. 

PMID- 25054357
TI  - Fluorescence-guided surgery for brain tumors.
AB  - 5-aminolevulinic acid-induced protoporphyrin IX fluorescence was authorized in
      the EU for visualization of tumor tissue during surgery for WHO grade III and IV
      gliomas in 2007. It facilitates tumor identification and doubles the number of
      gross total resections that can be achieved in these tumors. The growing
      acceptance of fluorescence-guided surgery in malignant gliomas brings forward a
      substantial yield of data on many types of intracranial lesions. The following
      review summarizes the main findings of these publications and illustrates the
      limitations, caveats and future perspectives of 5-aminolevulinic acid-induced
      fluorescence in malignant glioma as well as in other brain neoplasms.

PMID- 25054358
TI  - Current advances in understanding and managing secondary brain metastasis.
AB  - Metastatic brain tumors are the number one cause of intracranial neoplasms in
      adults and are associated with higher morbidity and mortality. The frequency of
      metastatic brain tumors is increasing because of improved survival in cancer
      patients. The molecular mechanism of brain metastasis is complex and not
      completely known. Vasogenic edema produced by tumor-derived VEGF is responsible
      for clinical symptoms. Dexamethasone remains the mainstay of medical management
      with not completely known mechanisms of action. Surgery and radiation are the
      main treatment modalities for metastatic brain tumors. Systemic chemotherapy has
      a very limited role in treatment of these tumors. Leptomeningeal metastasis is
      associated with extremely poor outcome.

PMID- 25054359
TI  - Strategies for overcoming the blood-brain barrier for the treatment of brain
      metastases.
AB  - The era of targeted therapy for cancer has been punctuated by some resounding
      successes, but with few exceptions, metastases to the brain remain frustratingly
      difficult to treat. It is increasingly apparent that old concerns regarding the
      ability of therapeutic agents to penetrate the blood-brain barrier have not been
      brushed aside by high-affinity small-molecule kinase inhibitors and monoclonal
      antibodies. Indeed, illustrative trends, such as the increasing incidence of
      brain metastases from HER2(+) breast cancer since the advent of trastuzumab
      therapy, have helped to solidify the concept of the CNS as a sanctuary site for
      cancer. With 200,000 patients diagnosed with brain metastases in the USA each
      year, the therapeutic challenge posed by the blood-brain barrier continues to be
      a big problem.

PMID- 25054360
TI  - Management of vestibular schwannoma: focus on vertigo.
AB  - This article reviews published literature on vertigo and a 'sense of imbalance'
      affecting patients who are treated with radiosurgery (RS) for vestibular
      schwannoma. This is a relatively understudied complaint, along with tinnitus, in
      this patient population, despite its significant impact on quality of life. It is
      also a symptom that is most inconsistently impacted by either RS or surgery. This
      article aims to highlight the importance of this symptom in patients managed for
      vestibular schwannoma primarily with RS to encourage a more systematic study of
      vertigo as an outcome measure and to help elucidate its potential etiology.

PMID- 25054362
TI  - Do patients with personality disorders respond differentially to
      electroconvulsive therapy? A review of the literature and consideration of
      conceptual issues.
AB  - Personality disorders are common among depressed patients. While there is
      considerable research demonstrating that such patients may respond less optimally
      to antidepressant medications, there is a relative dearth of research on the
      outcomes of depressed personality-disordered patients treated with
      electroconvulsive therapy (ECT). In this review, the author summarizes the
      available reports and concludes that there is reasonably robust evidence that
      patients with borderline personality disorder experience lesser antidepressant
      responses to ECT acutely and probably higher post-ECT relapse rates than
      depressed patients with other or no personality disorders. Some of the complex
      issues involved in selecting and treating such patients are discussed, and
      recommendations are provided for clinical practice and future research. 

PMID- 25054363
TI  - Combined ketamine/transcranial magnetic stimulation treatment of severe
      depression in bipolar I disorder.

PMID- 25054364
TI  - Electroconvulsive therapy service provision at Zomba Mental Hospital, Malawi.

PMID- 25054365
TI  - Using electron paramagnetic resonance to map N@C60 during high throughput
      processing.
AB  - The endohedral fullerene molecule, N@C60, is a candidate for molecular spin
      qubits (quantum bits) and spin probes owing to its exceptional electron spin
      properties. Advancements in the processing of N@C60 are key to obtaining samples
      of high purity on a reasonable timescale. We investigate enrichment by high
      throughput processing (flow rate of 18 L h(-1) and operating pressure of 1.5-2
      MPa) using high performance liquid chromatography (HPLC) as a means of scaling
      N@C60 production. We use detection by electron paramagnetic resonance (EPR)
      spectroscopy to map N@C60 during processing, and through the reconstruction of
      the peak position in the chromatogram, we are able to determine the retention
      time and relative purity of N@C60 without the need for its isolation. Based on
      this, we establish a procedure for time-efficient, high throughput processing to
      isolate N@C60 in high purity. 

PMID- 25054366
TI  - Positive psychology, utilitarianism and the pursuit of happiness.

PMID- 25054367
TI  - An investigation of the relationship between therapist characteristics and
      alliance in group therapy for individuals with treatment-resistant auditory
      hallucinations.
AB  - BACKGROUND: Alliance is a well-studied construct; however, little research has
      investigated predictors of alliance in a group context. AIMS: This study
      investigates the relationship between therapist characteristics and group
      alliance in 65 individuals with schizophrenia receiving outpatient group therapy
      for treatment-resistant auditory hallucinations. METHODS: Raters coded 120
      sessions of cognitive behavioral therapy or supportive therapy for therapist
      warmth and friendliness, therapist exploration and negative therapist attitude.
      Alliance was assessed at week six. RESULTS: Higher average levels of therapist
      warmth and friendliness and lower average levels of negative therapist attitude
      in sessions one to five were associated with stronger alliance at week six at the
      trend level (p < 0.10). Therapist exploration did not predict alliance at week
      six. Higher negative therapist attitude at treatment engagement was associated
      with higher post-treatment symptom scores. CONCLUSIONS: Our results suggest that
      therapist attributes but not therapist techniques are associated with client's
      perceptions of alliance and that negative therapist behaviors are associated with
      higher symptom levels at post-treatment. Implications for clinical practice are
      discussed.

PMID- 25054368
TI  - Financial motivation to work among people with psychiatric disorders.
AB  - BACKGROUND: Supported employment is an effective intervention for people with
      serious mental illnesses (SMI) but is underutilized. Clients' desire to work
      might be heightened by programs that provide counseling about managing one's
      funds, since money management helps people become more aware of the advantages of
      having money. AIM: To analyze the thoughts of recently homeless or hospitalized
      persons with SMI concerning their personal finances and employment. METHODS: We
      interviewed 49 people with SMI about their finances, reviewed transcripts and
      analyzed their baseline characteristics. RESULTS: Twenty of the 49 participants
      spontaneously expressed a desire to work in order to earn more money. Those who
      expressed a desire to work managed their money significantly better than those
      who did not. CONCLUSION: Discussion of finances, such as that fostered by money
      management programs, may promote engagement in vocational rehabilitation and
      working for pay.

PMID- 25054369
TI  - A systematic review of ethnic variations in hospital admission and compulsory
      detention in first-episode psychosis.
AB  - BACKGROUND: Marked ethnic variations in incidence, pathways to care and outcomes
      have been demonstrated in psychosis. Less research has focused specifically on
      first-episode psychosis (FEP), particularly adverse contacts such as compulsory
      detention and hospitalization. This is despite international initiatives to
      promote equity of care and active early intervention. AIM: Systematically review
      current evidence for ethnic variations in rates of compulsory admission and
      hospitalization in FEP. METHODS: Relevant articles published before December 2012
      were identified from PubMed, PSYCInfo, and CINAHL together with manual searching
      of reference lists. Studies providing quantitative data on compulsory detention
      rates and/or hospitalization, comparing ethnic groups in FEP, were included and
      quality rated by independent raters. RESULTS: All included studies (n = 7)
      provided data on compulsory detention while fewer (n = 3) focused on admission
      rates. Three studies reported increased detention in Black and minority ethnic
      groups, while one reported more hospitalization in White patients. Only two
      studies covered early intervention services (EIS). CONCLUSIONS: There is a
      paucity of high quality, well powered studies addressing this important issue,
      especially in EIS settings. In order to best inform and evaluate fast-developing
      services, it will be essential to combine large methodologically robust studies
      with qualitative analysis of patient, carer, and staff experiences.

PMID- 25054373
TI  - Cervical screening uptake and abnormalities among women attending sexual health
      clinics for HIV care.
AB  - The aim of this study was to describe cervical screening uptake and assess
      correlates of screen-detected abnormalities in women attending sexual health
      services for HIV care. Of 156 women, 115 had documentation of a Pap test at least
      once in 3 years and 9.6% had an annual Pap test performed. Pap abnormalities were
      associated with younger age, being born in Sub-Saharan Africa, more recent
      arrival in Australia, lower CD4 count, detectable viral load, shorter time on
      antiretroviral therapy and more recent HIV diagnosis. Women accessing sexual
      health services for HIV care, especially those from culturally and linguistically
      diverse backgrounds, appear to be substantially under-screened and efforts to
      optimise screening are needed. 

PMID- 25054374
TI  - Fertility preservation program before ovarotoxic oncostatic treatments: role of
      the psychological support in managing emotional aspects.
AB  - Fertility preservation programs (FPPs) based on oocyte or ovarian tissue
      cryostorage may be offered to women facing oncostatic treatments at risk of
      precocious ovarian insufficiency. The way in which FPPs are presented to patients
      affects their decision to join them. We studied herein 48 young women to whom a
      FPP was proposed, aiming at clarifying the emotional aspects involved. A
      psychologist attended the consultations in which the FPP was offered to patients;
      at the end of the talk, a questionnaire was administered and a semi-structured
      interview was carried out. Finally, the STAI test was administered to measure
      trait (TAI) and state (SAI) anxiety, both immediately after consultation, and
      later on, when patients returned home. We observed that the possibility to join a
      FPP implied important emotional aspects, and that the presence of a psychologist
      was helpful to integrate technical information and emotions as well as to reduce
      trait and state anxiety levels. Our study suggests that the presence of a
      psychologist during the meeting in which a FPP is offered improves communication
      between doctors and patients, and helps these women to get a full awareness
      before choosing to join the FPP.

PMID- 25054376
TI  - Lifestyle and healthy aging.

PMID- 25054375
TI  - Antioxidant effect of the active metabolites of tibolone.
AB  - Certain steroidal compounds have an antioxidant effect in humans. Our aim was to
      test whether the synthetic steroid tibolone and its metabolites are also able to
      display such a property. For this, granulocytes from healthy men and women were
      incubated for two hours with different concentrations (10(-7), 10(-8), 10(-9 )M)
      of either estradiol, tibolone, 3alpha-hydroxytibolone, 3beta-hydroxytibolone,
      Delta(4)-tibolone, 3alpha-sulfated-tibolone, 3alpha-17beta-disulfated-tibolone,
      3beta-sulfated-tibolone or 3beta-17beta-disulfated-tibolone. Superoxide anion
      generation of neutrophils was measured by photometry. Results of different
      steroids were given as percentages of their controls. A more simple superoxide
      generating system, the xanthine-xanthine oxidase reaction was also tested. We
      found that granulocyte superoxide production did not differ from the control
      using 10(-9 )M of steroids. Using 10(-8 )M concentration: estradiol (80.9 +/-
      2.5%); 3beta-sulfated-tibolone (83.3 +/- 4.7%); 3beta-17beta-disulfated-tibolone
      (81.0 +/- 4.2%) caused a significant decrease in superoxide production, compared
      to the control. In addition at 10(-7 )M, 3beta-hydroxytibolone and 3alpha
      sulfated-tibolone also showed antioxidant effects. In the xanthine-xanthine
      oxidase system estradiol (67.4 +/- 1.0%), 3alpha-sulfated-tibolone (85.8 +/-
      5.3%), 3alpha-17beta-disulfated-tibolone (71.9 +/- 2.5%), 3beta-sulfated-tibolone
      (73.9 +/- 5.0%), and 3beta-17beta-disulfated-tibolone (65.8 +/- 3.4%) caused a
      significant decrease in superoxide production. Conclusively, although tibolone
      itself did not show significant antioxidant capacity, most of its active
      metabolites have antioxidant effects.

PMID- 25054377
TI  - Polystyrene templated porous titania wells for quantum dot heterojunction solar
      cells.
AB  - Polystyrene spheres are used to template TiO2 with a single layer of 300 nm wells
      which are infilled with PbS quantum dots to form a heterojunction solar cell. The
      porous well device has an efficiency of 5.7% while the simple planar junction is
      limited to 3.2%. Using a combination of optical absorption and photocurrent
      transient decay measurement we determined that the performance enhancement comes
      from a combination of enhanced optical absorption and increased carrier lifetime.

PMID- 25054378
TI  - Immunomagnetic separation combined with inductively coupled plasma mass
      spectrometry for the detection of tumor cells using gold nanoparticle labeling.
AB  - This work reports an efficient, specific, and sensitive immunoassay protocol for
      detection of tumor cells by using inductively coupled plasma mass spectrometry
      (ICP-MS) with two probes. Magnetic nanobeads modified with anti-CD3 were used as
      capture probes for efficient and fast magnetic separation of Jurkat T cells from
      a mixture of cells, and gold nanoparticles (Au NPs) conjugated with anti-CD2 were
      used as detection probes for ICP-MS measurement. The capture and detection probes
      target the Jurkat T cells with high affinity and specificity, while they do not
      target other CD2/CD3-negative cells such as 97L cells and A549 cells. On the
      basis of these results, we proposed a new immunoassay for specific detection of
      Jurkat T cells. The conditions for this immunoassay were carefully optimized,
      including the incubation time and temperature, the concentration of the labeling
      probe, and the elution conditions. Under the optimized conditions, the linear
      range of 300-30,000 and the limit of detection of 86 Jurkat T cells were
      obtained, and the relative standard deviation for seven replicate detection of
      Jurkat T cells was 5.2% (3000 Jurkat T cells). This method has numerous
      advantages, including ease of preparation, low sample consumption, and high
      sensitivity and selectivity. Importantly, the methodology could be extended to
      the simultaneous detection of other cells based on their cellular biomarkers.

PMID- 25054379
TI  - The impact of meeting donor management goals on the number of organs transplanted
      per expanded criteria donor: a prospective study from the UNOS Region 5 Donor
      Management Goals Workgroup.
AB  - IMPORTANCE: The shortage of organs available for transplant has led to the use of
      expanded criteria donors (ECDs) to extend the donor pool. These donors are older
      and have more comorbidities and efforts to optimize the quality of their organs
      are needed. OBJECTIVE: To determine the impact of meeting a standardized set of
      critical care end points, or donor management goals (DMGs), on the number of
      organs transplanted per donor in ECDs. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective interventional study from February 2010 to July 2013 of all ECDs
      managed by the 8 organ procurement organizations in the southwestern United
      States (United Network for Organ Sharing Region 5). INTERVENTIONS: Implementation
      of 9 DMGs as a checklist to guide the management of every ECD. The DMGs
      represented normal cardiovascular, pulmonary, renal, and endocrine end points.
      Meeting the DMG bundle was defined a priori as achieving any 7 of the 9 end
      points and was recorded at the time of referral to the organ procurement
      organization, at the time of authorization for donation, 12 to 18 hours later,
      and prior to organ recovery. MAIN OUTCOMES AND MEASURES: The primary outcome
      measure was 3 or more organs transplanted per donor and binary logistic
      regression was used to identify independent predictors with P < .05. RESULTS:
      There were 671 ECDs with a mean (SD) number of 2.1 (1.3) organs transplanted per
      donor. Ten percent of the ECDs had met the DMG bundle at referral, 15% at the
      time of authorization, 33% at 12 to 18 hours, and 45% prior to recovery. Forty
      three percent had 3 or more organs transplanted per donor. Independent predictors
      of 3 or more organs transplanted per donor were older age (odds ratio [OR] = 0.95
      per year [95% CI, 0.93-0.97]), increased creatinine level (OR = 0.73 per mg/dL
      [95% CI, 0.63-0.85]), DMGs met prior to organ recovery (OR = 1.90 [95% CI, 1.35
      2.68]), and a change in the number of DMGs achieved from referral to organ
      recovery (OR = 1.11 per additional DMG [95% CI, 1.00-1.23]). CONCLUSIONS AND
      RELEVANCE: Meeting DMGs prior to organ recovery with ECDs is associated with
      achieving 3 or more organs transplanted per donor. An increase in the number of
      critical care end points achieved throughout the care of a potential donor by
      both donor hospital and organ procurement organization is also associated with an
      increase in organ yield.

PMID- 25054380
TI  - Niche partitioning in sympatric Gorilla and Pan from Cameroon: implications for
      life history strategies and for reconstructing the evolution of hominin life
      history.
AB  - Factors influencing the hominoid life histories are poorly understood, and little
      is known about how ecological conditions modulate the pace of their development.
      Yet our limited understanding of these interactions underpins life history
      interpretations in extinct hominins. Here we determined the synchronisation of
      dental mineralization/eruption with brain size in a 20th century museum
      collection of sympatric Gorilla gorilla and Pan troglodytes from Central
      Cameroon. Using delta13C and delta15N of individuals' hair, we assessed whether
      and how differences in diet and habitat use may have impacted on ape development.
      The results show that, overall, gorilla hair delta13C and delta15N values are
      more variable than those of chimpanzees, and that gorillas are consistently lower
      in delta13C and delta15N compared to chimpanzees. Within a restricted,
      isotopically-constrained area, gorilla brain development appears delayed relative
      to dental mineralization/eruption [or dental development is accelerated relative
      to brains]: only about 87.8% of adult brain size is attained by the time first
      permanent molars come into occlusion, whereas it is 92.3% in chimpanzees. Even
      when M1s are already in full functional occlusion, gorilla brains lag behind
      those of chimpanzee (91% versus 96.4%), relative to tooth development. Both
      bootstrap analyses and stable isotope results confirm that these results are
      unlikely due to sampling error. Rather, delta15N values imply that gorillas are
      not fully weaned (physiologically mature) until well after M1 are in full
      functional occlusion. In chimpanzees the transition from infant to adult feeding
      appears (a) more gradual and (b) earlier relative to somatic development. Taken
      together, the findings are consistent with life history theory that predicts
      delayed development when non-density dependent mortality is low, i.e. in closed
      habitats, and with the "risk aversion" hypothesis for frugivorous species as a
      means to avert starvation. Furthermore, the results highlight the complexity and
      plasticity of hominoid/hominin development. 

PMID- 25054381
TI  - Cervical and shoulder postural assessment of adolescents between 15 and 17 years
      old and association with upper quadrant pain.
AB  - BACKGROUND: There is sparse literature that provides evidence of cervical and
      shoulder postural alignment of 15 to 17-year-old adolescents and that analyzes
      sex differences. OBJECTIVES: To characterize the postural alignment of the head
      and shoulder in the sagittal plane of 15 to 17-year-old Portuguese adolescents in
      natural erect standing and explore the relationships between three postural
      angles and presence of neck and shoulder pain. METHOD: This cross-sectional study
      was conducted in two secondary schools in Portugal. 275 adolescent students (153
      females and 122 males) aged 15 to 17 were evaluated. Sagittal head, cervical, and
      shoulder angles were measured with photogrammetry and PAS software. The American
      Shoulder and Elbow Surgeons Shoulder Assessment (ASES) was used to assess
      shoulder pain, whereas neck pain was self-reported with a single question.
      RESULTS: Mean values of sagittal head, cervical, and shoulder angles were 17.2+/
      5.7, 47.4+/-5.2, and 51.4+/-8.5o, respectively. 68% of the participants revealed
      protraction of the head, whereas 58% of them had protraction of the shoulder. The
      boys showed a significantly higher mean cervical angle, and adolescents with neck
      pain revealed lower mean cervical angle than adolescents without neck pain. 53%
      of the girls self-reported regular neck pain, contrasting with 19% of the boys.
      CONCLUSIONS: This data shows that forward head and protracted shoulder are common
      postural disorders in adolescents, especially in girls. Neck pain is prevalent in
      adolescents, especially girls, and it is associated with forward head posture.

PMID- 25054382
TI  - Gait profile score and movement analysis profile in patients with Parkinson's
      disease during concurrent cognitive load.
AB  - BACKGROUND: Gait disorders are common in individuals with Parkinson's Disease
      (PD) and the concurrent performance of motor and cognitive tasks can have marked
      effects on gait. The Gait Profile Score (GPS) and the Movement Analysis Profile
      (MAP) were developed in order to summarize the data of kinematics and facilitate
      understanding of the results of gait analysis. OBJECTIVE: To investigate the
      effectiveness of the GPS and MAP in the quantification of changes in gait during
      a concurrent cognitive load while walking in adults with and without PD. METHOD:
      Fourteen patients with idiopathic PD and nine healthy subjects participated in
      the study. All subjects performed single and dual walking tasks. The GPS/MAP was
      computed from three-dimensional gait analysis data. RESULTS: Differences were
      found between tasks for GPS (P<0.05) and Gait Variable Score (GVS) (pelvic
      rotation, knee flexion-extension and ankle dorsiflexion-plantarflexion) (P<0.05)
      in the PD group. An interaction between task and group was observed for GPS
      (P<0.01) for the right side (Cohen's -d=0.99), left side (Cohen's -d=0.91), and
      overall (Cohen's -d=0.88). No interaction was observed only for hip internal
      external rotation and foot internal-external progression GVS variables in the PD
      group. CONCLUSIONS: The results showed gait impairment during the dual task and
      suggest that GPS/MAP may be used to evaluate the effects of concurrent cognitive
      load while walking in patients with PD.

PMID- 25054383
TI  - Relationship between static postural control and the level of functional
      abilities in children with cerebral palsy.
AB  - BACKGROUND: Postural control deficits can impair functional performance in
      children with cerebral palsy (CP) in daily living activities. OBJECTIVE: To
      verify the relationship between standing static postural control and the
      functional ability level in children with CP. METHOD: The postural control of 10
      children with CP (gross motor function levels I and II) was evaluated during
      static standing on a force platform for 30 seconds. The analyzed variables were
      the anteroposterior (AP) and mediolateral (ML) displacement of the center of
      pressure (CoP) and the area and velocity of the CoP oscillation. The functional
      abilities were evaluated using the mean Pediatric Evaluation of Disability
      Inventory (PEDI) scores, which evaluated self-care, mobility and social function
      in the domains of functional abilities and caregiver assistance. RESULTS:
      Spearman's correlation test found a relationship between postural control and
      functional abilities. The results showed a strong negative correlation between
      the variables of ML displacement of CoP, the area and velocity of the CoP
      oscillation and the PEDI scores in the self-care and caregiver assistance
      domains. Additionally, a moderate negative correlation was found between the area
      of the CoP oscillation and the mobility scores in the caregiver assistance
      domain. We used a significance level of 5% (p <0.05). CONCLUSIONS: We observed
      that children with cerebral palsy with high CoP oscillation values had lower
      caregiver assistance scores for activities of daily living (ADL) and consequently
      higher levels of caregiver dependence. These results demonstrate the
      repercussions of impairments to the body structure and function in terms of the
      activity levels of children with CP such that postural control impairments in
      these children lead to higher requirements for caregiver assistance.

PMID- 25054384
TI  - Content validation of a clinical assessment instrument for stair ascent and
      descent in individuals with hemiparesis.
AB  - BACKGROUND: Among the current instruments used to assess stair ambulation, none
      were observed that specifically evaluated the quality of movement or
      biomechanical strategies adopted by stroke patients. OBJECTIVE: To evaluate the
      content validity of a clinical instrument designed to identify the qualitative
      and kinematic characteristics and strategies adopted by stroke patients during
      stair ascent and descent. METHOD: The first developed version, which comprised 80
      items, had its content evaluated by an expert panel, which was composed of 9 well
      known national and international professionals who are involved in stroke
      rehabilitation. The content validity index (CVI) and modified Kappa coefficients
      were employed for the statistical analyses. The items that demonstrated a
      CVI>=0.80 and Kappa>=0.75 were considered valid. RESULTS: The content validation
      was performed in three stages. The final version of the instrument consisted of
      38 items, which were divided into descriptive (8 items), a General
      Characteristics Domain (16 items) and adopted strategies (14 items) during stair
      ascent and descent. The total scores ranged from zero to 70 and zero to 74 for
      ascent and descent, respectively. Lower scores corresponded with better
      performance. CONCLUSION: Despite the satisfactory results obtained during the
      process of content validation, other psychometric properties of the instrument
      are necessary and must be evaluated.

PMID- 25054385
TI  - Prevalence of musculoskeletal symptoms in hospital nurse technicians and licensed
      practical nurses: associations with demographic factors.
AB  - OBJECTIVE: This cross-sectional study aimed at analyzing: 1. the main
      musculoskeletal symptoms (MSS) presented by hospital nursing workers and; 2.
      personal, occupational, and health factors related to MSS among them. METHOD: Two
      questionnaires were filled in by 245 nurse technicians (NTs) and licensed
      practical nurses (LPNs) (response rate 95%) associated with direct patient care
      sectors from a hospital. These questionnaires were: the standardized version of
      the Nordic Musculoskeletal Questionnaire (NMQ) and one including questions on 15
      demographic independent variables potentially related to outcomes from the NMQ.
      Univariate analyses and binary logistic regression analyses were performed to
      identify which variables would explain the occurrence of MSS in different body
      regions. RESULTS: The low back (57%), shoulder (52%), and neck (48%) were
      identified as the most affected regions. The logistic regression analysis showed
      that low back symptoms in the last 12 months were significantly associated with
      LPN activities (OR=2.36; CI=1.24-4.5) and previous sick leave due to MSS
      (OR=5.97; CI=1.2-29.1). Smoking was significantly associated with symptoms in the
      low back (OR=2.77; CI=1.13-6.8) and thoracic spine (OR=2.37; CI=1.04-5.40).
      Physical exercise showed a protective effect on the cervical spine (OR=0.42;
      CI=0.23-0.77). Previous sick leave was significantly associated with pain in the
      knees (OR=4.24; CI=1.33-13.5) and in the upper limbs (OR=5.36; CI=1.07-26.7).
      CONCLUSIONS: The nursing workers who were evaluated presented a high prevalence
      of MSS. Previous history of sick leave was strongly associated with the presence
      of symptoms in various body regions. These results indicate the need for
      preventive programs in the hospital environment in order to control more severe
      MSS in nursing professionals.

PMID- 25054386
TI  - On the fourth Diadema species (Diadema-sp) from Japan.
AB  - Four long-spined sea urchin species in the genus Diadema are known to occur
      around the Japanese Archipelago. Three species (D. savignyi, D. setosum, and D.
      paucispinum) are widely distributed in the Indo-Pacific Ocean. The fourth species
      was detected by DNA analysis among samples originally collected as D. savignyi or
      D. setosum in Japan and the Marshall Islands and tentatively designated as
      Diadema-sp, remaining an undescribed species. We analyzed nucleotide sequences of
      the cytochrome oxidase I (COI) gene in the "D. savignyi-like" samples, and found
      all 17 individuals collected in the mainland of Japan (Sagami Bay and Kyushu) to
      be Diadema-sp, but all nine in the Ryukyu Archipelago (Okinawa and Ishigaki
      Islands) to be D. savignyi, with large nucleotide sequence difference between
      them (11.0%+/-1.7 SE). Diadema-sp and D. savignyi shared Y-shaped blue lines of
      iridophores along the interambulacrals, but individuals of Diadema-sp typically
      exhibited a conspicuous white streak at the fork of the Y-shaped blue iridophore
      lines, while this feature was absent in D. savignyi. Also, the central axis of
      the Y-shaped blue lines of iridophores was approximately twice as long as the V
      component in D. savignyi whereas it was of similar length in Diadema-sp. Two
      parallel lines were observed to constitute the central axis of the Y-shaped blue
      lines in both species, but these were considerably narrower in Diadema-sp.
      Despite marked morphological and genetic differences, it appears that Diadema-sp
      has been mis-identified as D. savignyi for more than half a century.

PMID- 25054387
TI  - Transforaminal versus parasagittal interlaminar epidural steroid injection in low
      back pain with radicular pain: a randomized, double-blind, active-control trial.
AB  - BACKGROUND: Epidural injections are the most common minimally invasive
      intervention used to manage low back pain with lumbosacral radicular pain. It can
      be delivered through either transforaminal (TF), interlaminar, or caudal
      approaches. The TF approach is considered more efficacious than the interlaminar
      approach probably because of ventral epidural spread. However, catastrophic
      complications reported with the TF approach have raised concerns regarding its
      use. These concerns regarding the safety of the TF approach lead to the search
      for a technically better route with lesser complications with drug delivery into
      the ventral epidural space. The parasagittal interlaminar (PIL) route is reported
      to have good ventral epidural spread. However, there is a paucity of literature
      comparing the effectiveness of PIL with TF. OBJECTIVES: To compare effectiveness
      of PIL and TF epidural injections for managing low back pain with lumbosacral
      radicular pain. STUDY DESIGN: Randomized, double-blind, active-control study.
      SETTING: Interventional pain management clinic in a tertiary care center in
      India. METHODS: Sixty-two patients were randomized to receive fluoroscopically
      guided epidural injection of methylprednisolone (80 mg) either through the PIL (n
      = 32) or TF (n = 30) approach. Patients were evaluated for effective pain relief
      (>= 50% from baseline) by 0 - 100 visual analogue scale (VAS) and functional
      improvement by Modified Oswestry Disability Questionnaire (MODQ) at 2 weeks, 1,
      2, 3, 6, 9, and 12 months. Patients who failed to respond to the treatment or
      when the patient's response deteriorated received additional injection of same
      injectate, dose, and approach. Only if the pain returns should there be a maximum
      of 3 injections. Other outcome measures were overall VAS and MODQ, number of
      injections, and presence of ventral and perineural spread. RESULTS: Effective
      pain relief (>= 50% pain relief from baseline on VAS) was observed in 76% (90% CI
      60.6 - 88.5%) of patients in the TF group and 78% (90% CI 62.8 - 89.3%) of
      patients in the PIL (P = 1.00) group at 3 months. The pain relief survival period
      was comparable in both groups (P = 0.98). Significant reduction in VAS and
      improvement in MODQ were observed at all time points post-intervention compared
      to baseline (P < 0.001) in both groups. On average, patients in the PIL group
      received 1.84 and patients in the TF group received 1.92 procedures annually. The
      majority received injection at L4-L5 intervertebral level (24 in TF and 23 in
      PIL). Ventral epidural spread was comparable in both groups (PIL - 91.6% and TF -
      89.6%). No major complications were encountered in either group; however, initial
      intravascular spread of contrast was observed in 3 patients in the TF group.
      LIMITATIONS: Limitations included lack of documentation of adjuvant analgesic
      drug therapy and procedures performed by a single experienced interventionalist.
      CONCLUSIONS: Epidural injection delivered through the PIL approach is equivalent
      in achieving effective pain relief and functional improvement to the TF approach
      for the management of low back pain with lumbosacral radicular pain. The PIL
      approach can be considered a suitable alternative to the TF approach for its
      equivalent effectiveness, probable better safety profile, and technical ease.
      TRIAL REGISTRATION: CTRI/2012/08/002938.

PMID- 25054388
TI  - Fluoroscopically guided infiltration of the cervical nerve root: an indirect
      approach through the ipsilateral facet joint.
AB  - Transforaminal infiltrations in the cervical spine are governed by a higher rate
      of vascular puncture than in the lumbar spine. The purpose of our study is to
      assess the safety and efficacy of percutaneous, fluoroscopically guided nerve
      root infiltrations in cases of cervical radiculopathy. An indirect postero
      lateral approach was performed through the ipsilateral facet joint. During the
      last 2 years, 25 patients experiencing cervical radiculopathy underwent
      percutaneous, fluoroscopically guided nerve root infiltrations by means of an
      indirect postero-lateral approach through the ipsilateral facet joint. The intra
      articular position of the needle (22-gauge spinal needle) was fluoroscopically
      verified after injection of a small amount of contrast medium which also verified
      dispersion of the contrast medium periradicularly and in the epidural space. Then
      a mixture of long-acting glucocorticosteroid diluted in normal saline (1.5/1 mL)
      was injected intra-articularly. A questionnaire with a Numeric Visual Scale (NVS)
      scale helped assess pain relief, life quality, and mobility improvement. A mean
      of 2.3 sessions was performed in the patients of our study. In the vast majority
      of our patients 19/25 (76%), the second infiltration was performed within 7-10
      days of the first one. Comparing the pain scores prior (mean value 8.80 +/- 1.080
      NVS units) and after (mean value 1.84 +/- 1.405 NVS units), there was a mean
      decrease of 6.96 +/- 1.695 NVS units [median value 7 NVS units (P < 0.001) in
      terms of pain reduction, effect upon mobility, and life quality. There were no
      clinically significant complications noted in our study. Fluoroscopically guided
      transforaminal infiltrations through the ipsilateral facet joint seem to be a
      feasible, efficacious, and safe approach for the treatment of patients with
      cervical radiculopathy. This approach facilitates needle placement and minimizes
      risk of complications.

PMID- 25054389
TI  - Adverse events associated with fluoroscopically guided zygapophyseal joint
      injections.
AB  - BACKGROUND: In spite of the widespread performance of intra-articular
      zygapophyseal joint (IAZJ) injections, we know of no systematic analysis to date
      that examines the risks and types of adverse events when IAZJ injections are
      performed. OBJECTIVE: To describe the type, incidence, and factors contributing
      to adverse events associated with fluoroscopically guided IAZJ injections. STUDY
      DESIGN: A retrospective, cohort study of English-speaking adults aged 18 - 90
      years who underwent fluoroscopically guided IAZJ injections between March 8,
      2004, and April 19, 2007. Following IAZJ injections, 3 senior researchers
      recorded the presence and type of adverse events. The relationship of adverse
      events with age, gender, fluoroscopy time, vital signs, and trainee presence was
      analyzed with Fisher's exact or Wilcoxon rank sum 2-sided tests. Frequency of
      immediate (during or immediately after the procedure) or delayed (within 24 - 72
      hours following the procedure) adverse events. SETTING: Tertiary, academic,
      outpatient physical medicine and rehabilitation interventional spine clinic.
      RESULTS: One hundred ninety-one patients (111 men) underwent 239 procedures. The
      mean and standard deviation (SD) of subject age was 56.4 (16.6) years ranging
      from 20 to 89. The mean and SD of pre-procedure 11-point Visual Analog Pain Scale
      was 5.5 (2.2) ranging from 0 to 10, and for post-procedure was 2.6 (2.6) ranging
      from 0 to 10. Trainees were involved in 52.3% of procedures. Reported immediate
      adverse events were vasovagal reaction (3.8%, n = 9) and steroid clogged needle
      (0.4%, n = 1). Follow-up data were available for 185/239 procedures (77.4%).
      There were 35 adverse events reported at mean follow-up interval of 1.8 days, of
      which the most frequent were injection site soreness (6.0%, n = 11), pain
      exacerbation (4.3%, n = 8), sleeplessness (2.2%, n = 4), and transient headache
      (1.6%, n = 3). Patient gender, age, trainee involvement, pre-procedural pain
      score, systolic or diastolic blood pressure, pulse, hemoglobin saturation as
      measured by pulse oximetry, volume of corticosteroid injected, and duration of
      fluoroscopy were not found to have a significant effect on immediate or delayed
      adverse events. LIMITATIONS: This study is limited by a 24- to 72-hour follow-up
      window, which may have also been too small to capture more delayed complications,
      and a sample size too small to accurately define the incidence of rare
      complications. CONCLUSION: Fluoroscopically guided IAZJ injections have minimal
      adverse effects. The most common immediate adverse event was vasovagal reaction
      and most common delayed adverse event was injection site soreness.

PMID- 25054390
TI  - Effect of thoracic epidural analgesia on pro-inflammatory cytokines in patients
      subjected to protective lung ventilation during Ivor Lewis esophagectomy.
AB  - BACKGROUND: Thoracic epidural analgesia (TEA) has a well-known effect on
      neurohormonal response. Attenuation of stress response by post-operative epidural
      analgesia has shown beneficial effects such as lower pain scores and less
      immunological alterations. OBJECTIVES: Investigation of the combined effects of
      TEA and protective lung ventilation on pro-inflammatory cytokines and patients'
      outcome after Ivor Lewis esophagectomy. STUDY DESIGN: A randomized controlled
      study. SETTING: Academic medical center. METHODS: Thirty patients of the American
      Society of Anesthesiologists (ASA) I and II were randomly allocated into 2
      groups: G1 (n = 15) patients received general anesthesia and were mechanically
      ventilated with 9 mL/kg during 2 lung ventilations, reduced to 5 mL/kg and 5cm
      H2O positive end expiratory pressure (PEEP) during one lung ventilation (OLV) or
      GII) (n = 15) patients received TEA and the same general anesthesia and
      mechanical ventilation used in G1. Assessment parameters included hemodynamics,
      pain severity, total analgesic consumption, and measurement of interleukins (IL)
      (IL-6 and IL-8) at baseline time after anesthetic induction (TBaseline,); at the
      end of the abdominal stage of the operation (TAbdo,); 15 minutes after initiation
      and at the end of OLV (TOLV 15) and (TOLV End) respectively; one and 20 hours
      after the end of the surgical procedure (TPostop1 and TPostop20), respectively,
      and patient's outcome also recorded. RESULTS: There was a significant reduction
      in mean arterial blood pressure (MAP) and pulse rate in GII during the
      intraoperative period, at Tabdo, TOLV15, and TOLV End (P < 0.05). The mean of
      systolic blood pressure (SBP) values were significantly lower in GII over all 3
      post-operative days (P = 0.001), and the mean diastolic blood pressure (DBP)
      showed a significant reduction in GII for 16 hours post-operatively (P = 0.001).
      The mean of heart rate values showed a significant reduction in GII over all 3
      post-operative days in comparison to GI (P = 0.001). The mean resting and dynamic
      VAS scores were significantly reduced in GII at all time periods studied in
      comparison to G1 (P = 0.001). The daily PCA morphine consumption was markedly
      decreased in GII compared to GI in the first 3 days post-operatively (P = 0.001).
      There were significant reductions in blood level of IL-6 and IL-8 in GII compared
      to G1 over the entire study period (P < 0.05). There were no significant
      differences in post-operative adverse effects between the 2 groups (P > 0.05).
      The duration of stay in PACU was significantly decreased in GII (10 +/- 2 days)
      compared to GI (15 +/- 3 days) (P = 0.001). LIMITATIONS: This study is limited by
      its sample size. CONCLUSION: Our study concluded that TEA reduced the systemic
      pro-inflammatory response and provided optimal post-operative pain relief.
      Although there were no significant differences in adverse events, there was a
      trend towards improved outcome. Further clinical studies with larger numbers of
      patients are required.

PMID- 25054391
TI  - Treatment of metastatic spinal lesions with a navigational bipolar radiofrequency
      ablation device: a multicenter retrospective study.
AB  - BACKGROUND: Spinal metastatic lesions are a common occurrence among oncology
      patients and contribute to significant morbidity. Treatment options have been
      limited in their effectiveness and scope to this point. OBJECTIVE: This study
      aims to report the safety and efficacy of radiofrequency ablation (RFA) of
      malignant spinal lesions using a novel RFA bipolar tumor ablation system which
      includes a navigational electrode containing 2 active thermocouples. STUDY
      DESIGN: IRB approved multicenter retrospective review of patients receiving RFA
      as a treatment of metastatic osseous lesions between March 2012 and March 2013.
      SETTING: This study consists of patients from 5 large academic centers. METHOD:
      One hundred twenty-eight metastatic lesions were identified in 92 patients who
      underwent a total of 96 procedures. Cement augmentation was performed when the
      vertebral body was at risk or had a pathological fracture. Visual analogue scale
      (VAS) scores were obtained preoperatively as well as postoperatively at the one
      week, one month, and 6 month time points. Interval change in the patients' pain
      medications was recorded. Postoperative imaging was used to assess tumor burden
      at the treated level when available. RESULTS: RFA was technically successful in
      all of the lesions without complication or thermal injury. Our study demonstrated
      significant (P < 0.01) decreases in the VAS scores at one week, one month, and 6
      months postoperatively. In our largest center, 54% of our patients experienced a
      decrease and 30% had no change in their pain medications postoperatively. Sixty
      two percent of the spinal lesions in this largest institution were located in the
      posterior vertebral body. Post-ablation imaging confirmed size of ablation zones
      consistent with that measured by the thermocouples. LIMITATIONS: The main
      limitations of this study are the heterogeneous patient population, data set, and
      potential confounding variable of concurrent cement augmentation. CONCLUSION: The
      STAR System is an RFA device that was safely and effectively used in the
      treatment of spine metastatic osseous lesions. This new device allows RFA
      treatment of previously untreatable lesions with resultant reduction in pain that
      was not controlled by systemic or radiation therapy.

PMID- 25054392
TI  - Tapentadol prolonged release for managing moderate to severe, chronic malignant
      tumor-related pain.
AB  - BACKGROUND: Tapentadol prolonged release (PR) is effective and well tolerated for
      chronic osteoarthritis, low back, and diabetic peripheral neuropathic pain.
      OBJECTIVES: To evaluate the efficacy and tolerability of tapentadol PR compared
      with placebo and morphine controlled release (CR) for managing moderate to severe
      chronic malignant tumor-related pain. STUDY DESIGN: Randomized-withdrawal,
      parallel group, active- and placebo-controlled, double-blind phase 3 study
      (NCT00472303). SETTING: Primary, secondary, and tertiary care settings in 16
      countries. METHODS: Eligible patients (pain intensity >= 5 [11-point numerical
      rating scale] on prior analgesics) were randomized (2:1) and titrated to their
      optimal dose of tapentadol PR (100-250 mg bid) or morphine sulfate CR (40-100 mg
      bid) over 2 weeks. Morphine sulfate immediate release 10 mg was permitted as
      needed for rescue medication (no maximum dose). Patients who completed titration
      and, during the last 3 days of titration, had mean pain intensity < 5 (based on
      twice-daily ratings) and mean rescue medication use = 20 mg/day continued into a
      4-week maintenance period; patients who received morphine CR during titration
      continued taking morphine CR, and those who received tapentadol PR were re
      randomized (1:1) to tapentadol PR or placebo bid. Response during maintenance
      (primary efficacy endpoint) was defined as having: (1) completed the maintenance
      period, (2) a mean pain intensity < 5 during maintenance, and (3) used an average
      of = 20 mg/day of rescue medication during maintenance. Response at the end of
      titration was defined similarly, with pain intensity and rescue medication
      averages based on the last 3 days of titration. RESULTS: Of 622 patients
      screened, 496 were randomized, treated during titration, and evaluable for
      safety; 327 were re-randomized, treated during maintenance, and evaluable for
      safety; and 325 were evaluable for efficacy. The adjusted responder rate estimate
      during maintenance (logistic regression adjusting for treatment group, pooled
      center, and pain intensity at start of maintenance) was significantly higher with
      tapentadol PR (64.3%) than with placebo (47.1%; odds ratio (OR), 2.02 [95%
      confidence interval (CI), 1.12 - 3.65]; P = 0.02). Based on responder rates at
      the end of titration, tapentadol PR (76.0% [174/229]) was non-inferior to
      morphine CR (83.0% [83/100]). The lower limit of the 95% CI for the between
      groups difference (-15.5%) was within the pre-specified 20% non-inferiority
      margin. During titration, incidences of treatment-emergent adverse events (TEAEs)
      were 50.0% (169/338) with tapentadol PR and 63.9% (101/158) with morphine CR;
      incidences of nausea, vomiting, and dry mouth were lower with tapentadol PR than
      with morphine CR. During maintenance, incidences of TEAEs were 56.3% (63/112),
      62.3% (66/106), and 62.4% (68/109) with placebo, tapentadol PR, and morphine CR,
      respectively. LIMITATIONS: Statistical comparisons between tapentadol PR and
      morphine CR were limited to descriptive statistics during the maintenance period
      because of the pre-selection of responders to tapentadol PR or morphine CR during
      titration. CONCLUSIONS: Results obtained during maintenance indicate that
      tapentadol PR (100-250 mg bid) is effective compared with placebo for managing
      moderate to severe chronic malignant tumor-related pain. Based on results
      obtained during titration, tapentadol PR provides comparable efficacy to that of
      morphine sulfate CR (40-100 mg bid), but is associated with better
      gastrointestinal tolerability.

PMID- 25054393
TI  - Effects of movement and postural positions in spinal cord stimulation in the new
      rechargeable systems.
AB  - BACKGROUND: Despite recent developments in implantable neurostimulation devices,
      the adjustment of stimulation levels to the patient's postural changes has
      remained a problem so far. OBJECTIVE: This study was conducted with the newest
      rechargeable devices, in order to compare its results with the ones published
      from conventional systems. STUDY DESIGN: It is a prospective study. SETTING: In
      46 patients implanted with rechargeable constant current stimulation systems we
      measured impedance, stimulation thresholds, therapeutic range, as well patients'
      satisfaction and sensation in 7 different body postures. RESULTS: Data analysis
      was performed in 46 patients, whose most frequent pathologies were failed back
      surgery syndrome (FBSS) and complex regional pain syndrome (CRPS). The lowest
      amplitude needed to reach the different thresholds was always scored in the
      supine decubitus position, with no significant changes in the therapeutic range
      and impedance. For all stimulation thresholds, there is always a difference
      between the supine position and all other postures. No statistically significant
      differences with regard to patients' satisfaction and sensation were found for
      the different postures. LIMITATIONS: Sample sample size. CONCLUSION: The findings
      of the present work are similar to those described in previous publications that
      showed the relationship between postural changes and several stimulation
      thresholds and pulse energy. The posture which requires lower energy - and whose
      corresponding therapeutic range (TR) is narrower--is supine decubitus.

PMID- 25054394
TI  - Increased thermal pain sensitivity in animals exposed to chronic high dose
      Vicodin but not pure hydrocodone.
AB  - Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one
      of the most prescribed drugs on the market today. Opioids have demonstrated the
      ability to paradoxically cause increased pain sensitivity to users in a phenomena
      called opioid-induced hyperalgesia (OIH). While selected opioids have been shown
      to produce OIH symptoms in an animal model, hydrocodone and the combination drug
      Vicodin have yet to be studied. The purpose of this study was to explore the
      effect of exposure to chronic high dose Vicodin or its components on the
      sensitivity to both thermal and mechanical pain. Animals were randomly divided
      into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and
      administered the drug daily for 120 days. Rats were subsequently tested for
      thermal and mechanical sensitivity. The rats in the Vicodin group displayed a
      significant decrease in withdrawal time to thermal pain. The rats receiving
      acetaminophen, hydrocodone, and vehicle showed no statistically significant
      hypersensitivity in thermal testing. None of the groups demonstrated
      statistically significant hypersensitivity to mechanical testing. The data
      suggests Vicodin produces signs of OIH in a rodent model. However, increased pain
      sensitivity was only noted in the thermal pathway and the hypersensitivity was
      only seen with the opioid combination drug, not the opioid alone. The results of
      this study both support the results of previous rodent opioid studies while
      generating further questions about the specific properties of Vicodin that
      contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic
      pain necessitates further research looking into this paradoxical pain response.

PMID- 25054395
TI  - KIMS, CEDIA, and HS-CEDIA immunoassays are inadequately sensitive for detection
      of benzodiazepines in urine from patients treated for chronic pain.
AB  - BACKGROUND: Patients treated for chronic pain may frequently undergo urine drug
      testing to monitor medication compliance and detect undisclosed prescribed or
      illicit drug use. Due to the increasing use and abuse of benzodiazepines, this
      class of medications is often included in drug screening panels. However,
      immunoassay-based methods lack the requisite sensitivity for detecting
      benzodiazepine use in this population primarily due to their poor cross
      reactivity with several major urinary benzodiazepine metabolites. A High
      Sensitivity Cloned Enzyme Donor Immunoassay (HS-CEDIA), in which beta
      glucuronidase is added to the reagent, has been shown to perform better than
      traditional assays, but its performance in patients treated for chronic pain is
      not well characterized. OBJECTIVES: To determine the diagnostic accuracy of HS
      CEDIA, as compared to the Cloned Enzyme Donor Immunoassay (CEDIA) and Kinetic
      Interaction of Microparticles in Solution (KIMS) screening immunoassays and
      liquid chromatography-tandem mass spectrometry (LC-MS/MS), for monitoring
      benzodiazepine use in patients treated for chronic pain. STUDY DESIGN: A study of
      the diagnostic accuracy of urine benzodiazepine immunoassays. SETTING: The study
      was conducted at an academic tertiary care hospital with a clinical laboratory
      that performs urine drug testing for monitoring medication compliance in pain
      management. METHODS: A total of 299 urine specimens from patients treated for
      chronic pain were screened for the presence of benzodiazepines using the HS
      CEDIA, CEDIA, and KIMS assays. The sensitivity and specificity of the screening
      assays were determined using the LC-MS/MS results as the reference method.
      RESULTS: Of the 299 urine specimens tested, 141 (47%) confirmed positive for one
      or more of the benzodiazepines/metabolites by LC-MS/MS. All 3 screens were 100%
      specific with no false-positive results. The CEDIA and KIMS sensitivities were
      55% (78/141) and 47% (66/141), respectively. Despite the relatively higher
      sensitivity of the HS-CEDIA screening assay (78%; 110/141), primarily due to
      increased detection of lorazepam, it still missed 22% (31/141) of benzodiazepine
      positive urines. The KIMS, CEDIA, and HS-CEDIA assays yielded accuracies of 75%,
      79%, and 90%, respectively, in comparison with LC-MS/MS. LIMITATIONS: This study
      was limited by its single-site location and the modest size of the urine samples
      utilized. CONCLUSIONS: While the HS-CEDIA provides higher sensitivity than the
      KIMS and CEDIA assays, it still missed an unacceptably high percentage of
      benzodiazepine-positive samples from patients treated for chronic pain. LC-MS/MS
      quantification with enzymatic sample pretreatment offers superior sensitivity and
      specificity for monitoring benzodiazepines in patients treated for chronic pain.

PMID- 25054396
TI  - Zohydro approval by food and drug administration: controversial or frightening?
AB  - The actions and regulations of the Food and Drug Administration (FDA) are crucial
      to the entire population of the U.S., specifically the public who take a
      multitude of drugs and providers who prescribe drugs and devices. Further, the
      FDA is relevant to investors, specifically in regards to biotech and
      pharmaceutical companies involved in developing new drugs. The FDA has been
      criticized for a lack of independence on the one hand and excessive regulatory
      and expanding authority without evidence and consistency of the actions on the
      other hand. The FDA approved a single-entity, long-acting, hydrocodone product
      (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation
      of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against
      the approval of Zohydro. Subsequent to the approval, multiple consumer safety
      organizations, health care agencies, addiction treatment providers, professional
      organizations, and other groups on the frontline of the opioid addiction epidemic
      have expressed concern. In addition, the US Congress and various state attorneys
      general raised serious concerns about the approval of Zohydro, which is highly
      addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro
      contend that it is necessary and essential to manage chronic pain and improve
      functional status with no additional risk. Over the past 15 years, prescriptions
      for opioids have skyrocketed with the United States consuming more than 84% of
      the global oxycodone and more than 99% of the hydrocodone supply. The sharp
      increase in opioid prescribing has led to parallel increases in opioid addiction
      and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies
      assessing the trends of medical use and misuse of opioid analgesics from 2000 to
      2011 have concluded that the present trend of the continued increase in the
      medical use of opioid analgesics appears to contribute to increasing misuse,
      resulting in multiple health consequences, despite numerous regulations enforced
      by multiple organizations. The approval of Zohydro and its defense from the FDA
      were based on a misunderstanding of the prevalence of chronic severe disabling
      pain. Based on inaccurate data from the Institute of Medicine, in part caused by
      conflicts of interest, 100 million persons have been described to suffer from
      severe pain - the correct number is 22.6 million. This manuscript analyzes 3
      important principles of drug approval and utilization based on safety, efficacy,
      and medical necessity. Based on the limited literature that the authors were able
      to review including that which was submitted to the FDA by the manufacturers, it
      appears the safety, efficacy, and medical necessity were not demonstrated. In
      fact, the study submitted to the FDA showed a 50% pain improvement in only 48% of
      the patients in the treatment group and 21% of the patients in the placebo group
      at 85 day follow-up. This is a statistically significant result but its clinical
      relevance is unknown. The FDA approval decision occurring against the backdrop of
      the advisory panel recommendation is concerning and may result in serious
      consequences in the future.

PMID- 25054397
TI  - Epidural steroid warning controversy still dogging FDA.
AB  - On April 23, 2014, the Food and Drug Administration (FDA) issued a letter of
      warning that injection of corticosteroids into the epidural space of the spine
      may result in rare, but serious adverse events, including "loss of vision,
      stroke, paralysis, and death." The advisory also advocated that patients should
      discuss the benefits and risks of epidural corticosteroid injections with their
      health care professionals, along with the benefits and risks associated with
      other possible treatments. In addition, the FDA stated that the effectiveness and
      safety of the corticosteroids for epidural use have not been established, and the
      FDA has not approved corticosteroids for such use. To raise awareness of the
      risks of epidural corticosteroid injections in the medical community, the FDA's
      Safe Use Initiative convened a panel of experts including pain management experts
      to help define the techniques for such injections with the aim of reducing
      preventable harm. The panel was unable to reach an agreement on 20 proposed items
      related to technical aspects of performing epidural injections. Subsequently, the
      FDA issued the above referenced warning and a notice that a panel will be
      convened in November 2014. This review assesses the inaccuracies of the warning
      and critically analyzes the available literature. The literature has been
      assessed in reference to alternate techniques and an understanding of the risk
      factors when performing transforaminal epidural injections in the cervical,
      thoracic, and lumbar regions, ultimately resulting in improved safety. The
      results of this review show the efficacy of epidural injections, with or without
      steroids, in a multitude of spinal ailments utilizing caudal, cervical, thoracic,
      and lumbar interlaminar approaches as well as lumbar transforaminal epidural
      injections . The evidence also shows the superiority of steroids in managing
      lumbar disc herniation utilizing caudal and lumbar interlaminar approaches
      without any significant difference as compared to transforaminal approaches,
      either with local anesthetic alone or local anesthetic and steroids combined. In
      conclusion, the authors request that the FDA modify the warning based on the
      evidence. 

PMID- 25054398
TI  - Randomized trial of epidural injections for spinal stenosis published in the New
      England Journal of Medicine: further confusion without clarification.
AB  - Randomized controlled trials are considered the hallmark of evidence-based
      medicine. This conveys the idea that up-to-date evidence applied consistently in
      clinical practice, in combination with clinicians' individual expertise and
      patients own preference/expectations are enjoined to achieve the best possible
      outcome. Since its inception in 1990s, evidence-based medicine has evolved in
      conjunction with numerous changes in the healthcare environment. However, the
      benefits of evidence-based medicine have not materialized for spinal pain
      including surgical interventions. Consequently, the debate continues on the
      efficacy and medical necessity of multiple interventions provided in managing
      spinal pain. Friedly et al published a randomized controlled trial of epidural
      glucocorticoid injections for spinal stenosis in the July 2014 edition of the
      highly prestigious New England Journal of Medicine. This was accompanied by an
      editorial from Andersson. This manuscript provided significant sensationalism for
      the media and confusion for the spine community. This randomized trial of
      epidural glucocorticoid injections for spinal stenosis and accompanying editorial
      concluded that epidural injections of glucocorticoids plus lidocaine offered
      minimal or no short-term benefit as compared with epidural injections of
      lidocaine alone, with the editorial emphasizing proceeding directly to surgical
      intervention. In addition media statements by the authors also emphasized the
      idea that exercise or surgery might be better options for patients suffereing
      from narrowing of the spinal canal. The interventional pain management community
      believes that there are severe limitations to this study, manuscript, and
      accompanying editorial. The design, inclusion criteria, outcomes assessment,
      analysis of data and interpretation, and conclusions of this trial point to the
      fact that this highly sophisticated and much publicized randomized trial may not
      be appropriate and lead to misinformation. The design of the trial was
      inappropriate with failure to include existing randomized trials, with inclusion
      criteria that did not incorporate conservative management,or caudal epidural
      injections. Simultaneously, acute pain patients were included, multilevel
      stenosis and various other factors were not identified. The interventions
      included lumbar interlaminar and transforaminal epidural injections with highly
      variable volumes of medication being injected per patient. Outcomes assessment
      was not optimal with assessment of the patients at 3 and 6 weeks for a procedure
      which provides on average 3 weeks of relief and utilizing an instrument which is
      more appropriately utilized in acute and subacute low back pain. Analysis of the
      data was hampered by inadequate subgroup analysis leading to inappropriate
      interpretation. Based on the available data epidural local anesthetic with
      steroids was clearly superior at 3 weeks and potentially at 6 weeks. Further,
      both treatments were effective considering the baseline to 3 week and 6 week
      assessment, appropriate subgroup analysis seems to have yielded significant
      superiority for interlaminar epidural injections compared to transforaminal
      epidural injections with local anesthetic with or without steroids specifically
      with proportion of patients achieving greater than 50% improvement at 3 and 6
      week levels. This critical assessment shows that this study suffers from a
      challenging design, was premised on the exclusion of available high-quality
      literature, and had inadequate duration of follow-up for an interventional
      technique with poor assessment criteria and reporting. Finally the analysis and
      interpretation of data has led to inaccurate and inappropriate conclusions which
      we do not believe is based on scientific evidence. 

PMID- 25054399
TI  - Transforaminal epidural injections in chronic lumbar disc herniation: a
      randomized, double-blind, active-control trial.
AB  - BACKGROUND: The estimated prevalence of lumbar radiculopathy has been described
      as 9.8 per 1,000 cases of low back pain. There are various surgical and
      nonsurgical modalities for treating lumbar disc herniation or radicular pain,
      including epidural injections. Epidural injection administration routes include
      transforaminal, interlaminar, and caudal approaches. The transforaminal approach
      requires the smallest volume to reach the primary site of pathology. Systematic
      reviews have yielded highly variable results, but a recent systematic review
      showed no significant difference among the 3 approaches. STUDY DESIGN: A
      randomized, controlled, double blind, active control trial. SETTING: An
      interventional pain management practice, a private specialty referral center in
      the United States. OBJECTIVES: To assess the effectiveness of transforaminal
      epidural injections of local anesthetic with or without steroids in managing
      chronic low back and lower extremity pain in patients with disc herniation and
      radiculitis. METHODS: One hundred twenty patients were randomly assigned to 2
      groups: Group I received 1.5 mL of 1% preservative-free lidocaine, followed by
      0.5 mL of sodium chloride solution. Group II received 1% lidocaine, followed by 3
      mg, or 0.5 mL of betamethasone. The sodium chloride solution and betamethasone
      were either clear liquids or were provided in opaque-covered syringes. OUTCOMES
      ASSESSMENT: The primary outcome measure was significant improvement (at least
      50%) measured by the average Numeric Rating Scale (NRS) and the Oswestry
      Disability Index 2.0 (ODI). Secondary outcome measures were employment status and
      opioid intake. RESULTS: At 2 years there was significant improvement in all
      participants in 65% who received local anesthetic alone and 57% who received
      local anesthetic and steroid. When separated into non-responsive and responsive
      categories based on initial relief of at least 3 weeks with 2 procedures,
      significant improvement (at least 50% improvement in pain and function) was seen
      in 80% in the local anesthetic group and 73% in the local anesthetic with steroid
      group. LIMITATIONS: Presumed limitations of this evaluation include the lack of a
      placebo group. CONCLUSION: Transforaminal epidural injections of local anesthetic
      with or without steroids might be an effective therapy for patients with disc
      herniation or radiculitis. The present evidence illustrates the lack of
      superiority of steroids compared with local anesthetic at 2-year follow-up.

PMID- 25054400
TI  - Opioid tolerance--a predictor of increased length of stay and higher readmission
      rates.
AB  - The increasing use of opioids to manage pain in the United States over the last
      decade has resulted in a subset of our population developing opioid tolerance.
      While the management of opioid tolerant patients during acute episodes of care is
      well known to be a challenge amongst health care providers, there is little in
      the literature that has studied opioid tolerance as a predictor of outcomes. We
      conducted a review on all admissions to Massachusetts General Hospital over a
      period of 6 months, from January 2013 to June 2013, and identified opioid
      tolerant patients at admission using the FDA definition of opioid tolerance. To
      compare risk adjusted groups, we placed opioid tolerant patients and control
      patients into groups determined by expected length of stay of less than 2 days, 2
      to 5 days, 5 to 10 days, and greater than 10 days. Opioid tolerant patients were
      then compared to the control for outcomes measures including observed length of
      stay and readmission rates. Our results show that all opioid tolerant patients
      have a significantly longer length of stay and a greater 30 day all cause
      readmission rate than the control group (P < 0.01). This trend was found in the
      first 3 risk adjusted groups, but not in the fourth group where expected length
      of stay was greater than 10 days. The opioid tolerant population is at risk given
      the poorer outcomes and higher health care costs associated with their care. It
      is imperative that we identify opportunities for improvement and delineate
      specific pathways for the care of these patients. 

PMID- 25054401
TI  - Transforaminal versus interlaminar approaches to epidural steroid injections: a
      systematic review of comparative studies for lumbosacral radicular pain.
AB  - BACKGROUND: The superiority of transforaminal epidural steroid injections (TFESI)
      vs. interlaminar epidural steroid injections (ILESI) for treating unilateral
      lumbosacral radicular pain (LSRP) is unproven. OBJECTIVE: To assess studies
      comparing TFESI to ILESI for unilateral LSRP for pain relief and functional
      improvement. STUDY DESIGN: Systematic review of comparative studies. METHODS: A
      systematic literature search was conducted using the Cochrane Central Register of
      Controlled Trials, PubMed, and Scopus databases for trials reported in English.
      Studies meeting the Cochrane Review criteria for randomized trials and the AHCQ
      criteria for observational studies were included. Evidence was graded using the
      USPSTF classification. RESULTS: Five (prospective) and 3 (retrospective) studies
      were included assessing 506 patients. Statistical analysis was calculated only
      utilizing the 5 prospective studies and consisted of 249 patients with an average
      of 3.2 months follow-up. In the short-term (2 weeks), there was a 15% difference
      favoring TFESI vs. ILESI for pain relief. There was no efficacy difference at one
      or 6 months. Combined pain improvements in all 5 prospective studies revealed <
      20% difference between TFESI and ILESI (54.1% vs. 42.7%). There was slightly
      better functional improvement in ILESI groups (56.4%) vs. TFESI groups (49.4%) at
      2 weeks. Combined data showed slight differences (TFESI 40.1% and ILESI 44.8%).
      LIMITATIONS: The limitations of this systematic review include the relative
      paucity of comparative studies. CONCLUSIONS: The findings show that both TFESI
      and ILESI are effective in reducing pain and improving functional scores in
      unilateral LSRP. In the treatment of pain, TFESI demonstrated non-clinically
      significant superiority to ILESI only at the 2-week follow-up. Based on 2
      studies, ILESI demonstrated non-clinically significant superiority to TFESI in
      functional improvement.

PMID- 25054402
TI  - Human umbilical cord mesenchymal stem cell transplantation for the treatment of
      chronic discogenic low back pain.
AB  - BACKGROUND: Chronic low back pain is one of the major causes of disability and
      thus has a major socioeconomic impact. Intervertebral disc degeneration is the
      main cause of chronic low back pain. Treatment for chronic discogenic low back
      pain has traditionally been limited to either conservative management or surgical
      fusion. If conservative treatment fails, then surgical fusion is commonly
      considered. Current treatments are limited to treat the symptoms and not the
      underlying biologic alterations of the disc. OBJECTIVE: Human umbilical cord
      tissue-derived mesenchymal stem cells (HUC-MSCs) contain stem cells and possess
      the ability to regenerate degenerative discs. Based on the results of previous in
      vitro and animal experiments, we conducted a preliminary study to test the
      feasibility and safety and to obtain an early indication for the therapeutic
      value of HUC-MSC transplantation in patients with chronic discogenic low back
      pain. STUDY DESIGN: This is the first study involving treatment of chronic low
      back pain using HUC-MSC transplantation. SETTING: The study was performed at a
      spine center in China. METHODS: Two patients with chronic discogenic low back
      pain were treated with HUC-MSC transplantation. An 11-point visual analog scale
      (VAS, 0-10) and Oswestry Disability Index (ODI, 0-100) were used to assess the
      back pain symptoms and the lumbar function, respectively. RESULTS: After
      transplantation, the pain and function improved immediately in the 2 patients.
      The VAS and ODI scores decreased obviously during a 2-year follow-up period.
      LIMITATIONS: The shortcoming of this study is that it is a preliminary study with
      only 2 patients. CONCLUSION: The clinical outcomes indicated that HUC-MSC
      transplantation is a favorable alternative method for the treatment of chronic
      discogenic low back pain.

PMID- 25054403
TI  - Neuromodulation of the great auricular nerve for persistent post-traumatic
      headache.
AB  - Headache is the most frequent reason for referral to an outpatient neurology and
      pain physician practice, with post-traumatic headache (PTH) accounting for
      approximately 4% of all symptomatic headaches. Headache following trauma has been
      reported for centuries. In this unique case report we will discuss the clinical
      course and successful headache treatment of a 57-year-old man diagnosed with
      PTHs. He suffered from chronic, intractable headaches resistant to
      multidisciplinary medical management for 4 years. A trial of electrical
      neuromodulation of the C2-C3 branches within the great auricular nerve (GAN)
      distribution was proposed as a potential long-term treatment for his chronic,
      intractable headaches after having several prior headache attacks successfully
      aborted with ultrasound-guided GAN blocks. Six months after permanent peripheral
      neurostimulator implantation, the patient reported a greater than 90% reduction
      in headache frequency, and was able to wean off all his previous prophylactic and
      abortive headache medications, with the exception of over-the-counter ibuprofen
      as needed. Subcutaneous electrode application over the branches of C2-C3-namely
      greater, lesser, and the least occipital nerves-for the treatment of chronic,
      intractable headache is not a new concept within pain medicine literature.
      However, subcutaneous electrode application, specifically over the GAN, is
      unique. The following case report chronicles the novel application of ultrasound
      guided peripheral nerve stimulation of the GAN as an effective and safe long-term
      treatment for chronic, intractable primary headache. The positive outcome
      chronicled in this case presentation suggests that peripheral nerve stimulation
      of the GAN should be considered for highly select cases. To our knowledge, this
      is the first such case report describing GAN as a target for the management of
      PTH in the literature. 

PMID- 25054404
TI  - High cervical epidural neurostimulation for post-traumatic headache management.
AB  - Headache following head injuries has been reported for centuries. The majority of
      post-traumatic headache (PTH) patients will report resolution of their complaints
      within a few months from the time of the initial injury. PTHs can contribute to
      disability, lost productivity, and health care costs. In this article we discuss
      a 40-year-old male with a history of motor vehicle accident and basal skull
      fracture. The patient had no headache history prior to the accident. He presented
      with more than 3 years persistent daily headache. The patient described constant
      throbbing and stabbing quality headaches predominantly on the left hemicranium
      with constant facial pain. He denies having aura, nausea, or vomiting, but
      reported occasional neck tightness. An extensive workup was carried out under the
      direction of the patient's primary neurologist. Secondary to persistent
      intractable pain, the patient was referred to the pain clinic for further
      evaluation. As his headaches were resistant to all trialed strategies, we decided
      to turn our therapeutic focus toward electrical neuromodulation along with
      continuing multimodal medications and multidisciplinary approach. During 7 days
      of high cervical dorsal column electrical nerve stimulation trial, he reported
      almost 90% pain reduction and significant improvement on his quality of life. On
      12 months follow-up after he underwent a permanent implant of high cervical
      dorsal column electrical nerve stimulation, he reported the same level of pain
      reduction along with 100% satisfaction rate. To the best of our knowledge, there
      have been no publications to date concerning the application of high cervical
      nerve stimulation for PTH. 

PMID- 25054405
TI  - Androgen deficiency in long-term intrathecal opioid administration.
AB  - BACKGROUND: Intrathecal drug delivery of opioids is an efficient and effective
      treatment option for pain management in the chronic nonmalignant pain population.
      As with all treatments, in addition to the benefits, risks and side effects
      exist. One such risk in intrathecal opioids is opioid-induced androgen
      deficiency. OBJECTIVE: This study evaluates opioid-induced androgen deficiency in
      long-term intrathecal opioid administration in chronic nonmalignant pain. STUDY
      DESIGN: Case series. Sixteen consecutive patients with intrathecal drug delivery
      with opioids were screened for androgen deficiency. SETTING: Academic university
      based pain management center. METHOD: All the subjects were seen in a 2 month
      period, during a scheduled maintenance refill visit. Eight consecutive men and
      eight consecutive women receiving intrathecal drug delivery therapy for non
      malignant chronic pain were ordered blood work and asked to complete a
      questionnaire. Patient and patient-related data were also collected. RESULTS: Ten
      of the 16 (62.5%) patients were found to have androgen deficiency, 4 of 8 men
      based on free testosterone levels and 6 of 8 women based on DHEA levels. In men,
      erectile dysfunction correlated with endocrine dysfunction (P = 0.02) while
      depressive symptoms correlated in women (P = .03). Overall, 2 of the 16 patients
      had hydromorphone as the opioid in the intrathecal system. Both patients had
      normal endocrine functions. Both patients with hydromorphone were men and the use
      of hydromorphone showed an insignificant trend (P = 0.06). Three of the 4 men
      with normal endocrine functions had in addition to an opioid, bupivacaine, in the
      intrathecal system. The presence of bupivicaine in men was significant (P =
      0.02). No women had bupivicaine while one of the 8 women had clonidine in
      addition to the opioid. Presence of another substance in addition to the opioid
      showed an insignificant trend (P = 0.08). LIMITATIONS: Study limitations include
      the small sample size and case series nature. Additionally the symptoms data was
      solely based on subjective patient reports. CONCLUSIONS: Androgen deficiency is
      common in patients treated with intrathecal opioids for chronic nonmalignant
      pain. Patients experience numerous and wide ranging symptoms. Erectile
      dysfunction may be more suggestive for androgen deficiency in men while
      complaints of depressed mood may be correlative in women. Additionally, combining
      bupivicaine with the intrathecal opioid may provide a protective role.

PMID- 25054406
TI  - The Food and Drug Administration's recent action on April 23, 2014 failed to
      appropriately address safety concerns about epidural steroid use.

PMID- 25054407
TI  - Serratus anterior plane block for multiple rib fractures.

PMID- 25054408
TI  - Ultrasound imaging for the upper limb nerves in CRPS: a patient with electrical
      injury.

PMID- 25054409
TI  - Agroinfiltration by cytokinin-producing Agrobacterium sp. strain GV3101 primes
      defense responses in Nicotiana tabacum.
AB  - Transient infiltrations in tobacco are commonly used in plant studies, but the
      host response to different disarmed Agrobacterium strains is not fully
      understood. The present study shows that pretreatment with disarmed Agrobacterium
      tumefaciens GV3101 primes the defense response to subsequent infection by
      Pseudomonas syringae in Nicotiana tabacum. The presence of a trans-zeatin
      synthase (tzs) gene in strain GV3101 may be partly responsible for the priming
      response, as the tzs-deficient Agrobacterium sp. strain LBA4404 only weakly
      imparts such responses. Besides inducing the expression of defense-related genes
      like PR-1 and NHL10, GV3101 pretreatment increased the expression of tobacco
      mitogen-activated protein kinase (MAPK) pathway genes like MEK2, WIPK (wound
      induced protein kinase), and SIPK (salicylic acid-induced protein kinase).
      Furthermore, the GV3101 strain showed a stronger effect than the LBA4404 strain
      in activating phosphorylation of the tobacco MAPK, WIPK and SIPK, which
      presumably prime the plant immune machinery. Lower doses of exogenously applied
      cytokinins increased the activation of MAPK, while higher doses decreased the
      activation, suggesting a balanced level of cytokinins is required to generate
      defense response in planta. The current study serves as a cautionary warning for
      plant researchers over the choice of Agrobacterium strains and their possible
      consequences on subsequent pathogen-related studies.

PMID- 25054410
TI  - Rh(III)-catalyzed intramolecular redox-neutral or oxidative cyclization of
      alkynes: short, efficient synthesis of 3,4-fused indole skeletons.
AB  - A Rh(III)-catalyzed intramolecular redox-neutral or oxidative annulation of a
      tethered alkyne has been developed to efficiently construct 3,4-fused indoles via
      a C-H activation pathway. The advantages of this process are (1) ready
      availability of annulation precursors; (2) broad substrate scope; (3) complete
      regioselectivity; (4) simple and mild reaction conditions; and (5) no need for an
      external oxidant or to employ molecular oxygen as the stoichiometric terminal
      oxidant. 

PMID- 25054411
TI  - Phase diagram study of a dimerized spin-S zig-zag ladder.
AB  - The phase diagram of a frustrated spin-S zig-zag ladder is studied through
      different numerical and analytical methods. We show that for arbitrary S, there
      is a family of Hamiltonians for which a fully-dimerized state is an exact ground
      state, being the Majumdar-Ghosh point for a particular member of the family. We
      show that the system presents a transition between a dimerized phase to a Neel
      like phase for S = 1/2, and spiral phases can appear for large S. The phase
      diagram is characterized by means of a generalization of the usual mean field
      approximation. The novelty in the present implementation is to consider the
      strongest coupled sites as the unit cell. The gap and the excitation spectrum is
      analyzed through the random phase approximation. Also, a perturbative treatment
      to obtain the critical points is discussed. Comparisons of the results with
      numerical methods like the Density Matrix Renormalization Group are also
      presented.

PMID- 25054412
TI  - Discussing the undiscussable with the powerful: why and how faculty must learn to
      counteract organizational silence.
AB  - Dialogue is essential for transforming institutions into learning organizations,
      yet many well-known characteristics of academic health centers (AHCs) interfere
      with open discussion. Rigid hierarchies, intense competition for resources, and
      the power of peer review in advancement processes all hamper difficult
      conversations, thereby contributing to organizational silence, and at great cost
      to the institution. Information necessary for critical decisions is not shared,
      individuals and the organization do not learn from mistakes, and diverse
      perspectives from those with less power are not entertained, or worse, are
      suppressed. When leaders become more skilled at inviting multiple perspectives
      and faculty more adept at broaching difficult conversations with those in power,
      differences are more effectively addressed and conflicts resolved. In this
      article, the authors frame why this skill is an essential competency for faculty
      and leaders alike and provide the following recommendations to institutions for
      increasing capacity in this area: (1) develop leaders to counteract
      organizational silence, (2) develop faculty members' skills in raising difficult
      issues with those in positions of power, and (3) train mentors to coach others in
      raising difficult conversations. The vitality of AHCs requires that faculty and
      institutional leaders develop relational communication skills and partner in
      learning through challenging conversations. 

PMID- 25054413
TI  - Medical interpreters: improvements to address access, equity, and quality of care
      for limited-English-proficient patients.
AB  - Limited-English-proficient (LEP) patients in the United States experience a
      variety of health care disparities associated with language barriers, including
      reduced clinical encounter time and substandard medical treatment compared with
      their English-speaking counterparts. In most current U.S. health care settings,
      interpretation services are provided by personnel ranging from employed
      professional interpreters to untrained, ad hoc interpreters such as friends,
      family, or medical staff. Studies have demonstrated that untrained individuals
      commit many interpretation errors that may critically compromise patient safety
      and ultimately prove to be life-threatening. Despite documented risks, the U.S.
      health care system lacks a required standardized certification for medical
      interpreters. The authors propose that the standardization of medical interpreter
      training and certification would substantially reduce the barriers to equitable
      care experienced by LEP patients in the U.S. health care system, including the
      occurrence of preventable clinical errors. Recent efforts of the U.S. federal
      court system are cited as a successful and realistic example of how these goals
      may be achieved. As guided by the evolution of the federal court interpreting
      certification program, subsequent research will be required to demonstrate the
      improvements and challenges that would result from national certification
      standards and policy for medical interpreters. Research should examine cost
      effectiveness and ensure that certified interpreting services are appropriately
      used by health care practitioners. Ongoing commitment is required from lawmakers,
      health care providers, and researchers to remove barriers to care and to demand
      that equity remain a consistent goal of our health care system.

PMID- 25054414
TI  - Graduate medical education's new focus on resident engagement in quality and
      safety: will it transform the culture of teaching hospitals?
AB  - The Accreditation Council for Graduate Medical Education recently announced its
      Clinical Learning Environment Review (CLER) program, which is designed to
      catalyze and promote the engagement of physician trainees in health care quality
      and patient safety activities that are essential to the delivery of high-quality
      patient care in U.S. teaching hospitals. In this Commentary, the authors argue
      that a strong organizational culture in quality improvement and patient safety is
      a necessary foundation for resident engagement in these areas. They describe
      residents' influence via their social networks on the behaviors and attitudes of
      peers and other health care providers and highlight this as a powerful driver for
      culture change in teaching hospitals. They also consider some of the potential
      unintended consequences of the CLER program and offer strategies to avoid them.
      The authors suggest that the CLER program provides an opportunity for health care
      and graduate medical education leaders to closely examine organizational quality
      and safety culture and the degree to which their residents are integrated in
      these efforts. They highlight the importance of developing collaborative
      interprofessional strategies to reach common goals to improve patient care. By
      sharpening the focus on patient safety, supervision, professionalism, patient
      care transitions, and the overall quality of health care delivery in the clinical
      learning environment during residents' formative training years, the hope is that
      the CLER program will inspire a new generation of physicians who possess and
      value these skills.

PMID- 25054415
TI  - Assessing medical students' and residents' perceptions of the learning
      environment: exploring validity evidence for the interpretation of scores from
      existing tools.
AB  - PURPOSE: Although most agree that supportive learning environments (LEs) are
      essential for effective medical education, an accurate assessment of LE quality
      has been challenging for educators and administrators. Two previous reviews
      assessed LE tools used in the health professions; however, both have
      shortcomings. The primary goal of this systematic review was to explore the
      validity evidence for the interpretation of scores from LE tools. METHOD: The
      authors searched ERIC, PsycINFO, and PubMed for peer-reviewed studies that
      provided quantitative data on medical students' and/or residents' perceptions of
      the LE published through 2012 in the United States and internationally. They also
      searched SCOPUS and the reference lists of included studies for subsequent
      publications that assessed the LE tools. From each study, the authors extracted
      descriptive, sample, and validity evidence (content, response process, internal
      structure, relationship to other variables) information. They calculated a total
      validity evidence score for each tool. RESULTS: The authors identified 15 tools
      that assessed the LE in medical school and 13 that did so in residency. The
      majority of studies (17; 61%) provided some form of content validity evidence.
      Studies were less likely to provide evidence of internal structure, response
      process, and relationship to other variables. CONCLUSIONS: Given the limited
      validity evidence for scores from existing LE tools, new tools may be needed to
      assess medical students' and residents' perceptions of the LE. Any new tools
      would need robust validity evidence testing and sampling across multiple
      institutions with trainees at multiple levels to establish their utility.

PMID- 25054416
TI  - Behind bars: the compelling case for academic health centers partnering with
      correctional facilities.
AB  - Academic health centers (AHCs), particularly those that are publicly funded
      institutions, have as their mission the treatment of disadvantaged populations,
      the training of the next generation of clinicians, and the development and
      dissemination of new knowledge to reduce the burden of disease and improve the
      health of individuals and populations. Incarcerated populations have the most
      prevalent and acute disease burden and health disparities in the United States,
      even in comparison with inner-city populations. Yet, only a small proportion of
      AHCs have reached out to incarcerated populations to fulfill their mission. Those
      AHCs that have partnered with correctional facilities have overcome concerns
      about the value and popularity of "training behind bars"; the cost, liability,
      and pragmatics of caring for a medically complicated population; and the
      viability of correctional health research and extramural research funding. They
      have done so to great benefit to patients, students, and faculty. Partnering with
      correctional facilities to provide health care offers opportunities for AHCs to
      fulfill their core missions of clinical service, education, and research, while
      also enhancing their financial stability, to the benefit of all. In this
      Commentary, the authors discuss, based on their experiences, these concerns, how
      existing partnerships have overcome them, and the benefits of such relationships
      to both AHCs and correctional facilities. 

PMID- 25054417
TI  - Can we learn civility? Reflections on the challenge of changing culture.
AB  - Academic medicine shares the handicap of many hierarchical organizations in that
      it is difficult for those lower in the hierarchy to speak up when doing so
      requires challenging their chronologic and administrative elders. Elsewhere in
      this issue, Dankoski and colleagues offer specific recommendations for combating
      this "organizational silence," including training and mentorship for junior
      faculty. In this related Commentary, the authors cite their lack of success with
      isolated initiatives to address the problem of organizational silence in their
      own institution. They suggest that nothing short of a comprehensive, visible,
      high-priority organizational commitment to culture change is likely to be
      effective in facilitating respectful and candid communication up and down the
      academic hierarchy. Until the culture of academic medicine affirms that broad
      input is vital, learners and junior faculty are unlikely to feel safe in
      expressing concerns, providing feedback, reporting mistreatment or unprofessional
      behaviors, and offering suggestions for improvement. 

PMID- 25054418
TI  - "Medical education is the ugly duckling of the medical world" and other
      challenges to medical educators' identity construction: a qualitative study.
AB  - PURPOSE: The authors first aimed to ascertain how the Academy of Medical
      Educators (AoME) could develop and support early career medical educators. They
      expanded their study to explore the challenges to defining medical education as a
      discipline because of a lack of collective identity among educators. METHOD: In
      2010, the authors and members of the AoME Early Careers Working Group conducted
      focus groups with early career medical educators (clinicians and scientists) and
      interviews with senior medical educators in the United Kingdom. All focus groups
      and interviews were audio recorded and transcribed verbatim. The authors used an
      interpretative phenomenological analysis to explore how medical educators
      described events or phenomena in their careers. They inductively identified
      overarching theoretical perspectives to understand observed phenomena drawing on
      social identity theories. RESULTS: The authors conducted nine focus groups with
      34 participants in total and six interviews. Participants identified fundamental
      challenges to their identity as a medical educator; they understood their medical
      education role to be secondary to their primary role as clinician or scientist.
      Participants noted that they had not developed an emotional attachment to medical
      education. Their relationship with the field remained at an operational level,
      revolving around roles and responsibilities. CONCLUSIONS: Medical educators'
      social cohesion is threatened by their sense that educators are poor relations
      compared with scientists and clinicians. While medical educators' identities may
      be in crisis, they also are changing, a change needed for medical education,
      medical education research, the practice of medicine, and ultimately patient
      care.

PMID- 25054419
TI  - Connecting resident education to patient outcomes: the evolution of a quality
      improvement curriculum in an internal medicine residency.
AB  - As part of the Accreditation Council for Graduate Medical Education's Next
      Accreditation System, residency programs must connect resident-physician
      education to improved patient care outcomes. Residency training programs,
      however, face multiple obstacles in doing so. Results from residency quality
      improvement (QI) curricula tend to show improvement in simple process-based
      measures but not in more complex outcomes of care such as diabetes or blood
      pressure control. In this article, the authors describe the evolution of their QI
      educational program for internal medicine residents at the University of
      Cincinnati Medical Center within the structure of a novel training model called
      the Ambulatory Long Block. They discuss a resident-run project that led to
      reduced rates of patients with uncontrolled diabetes as an example of improvement
      in outcome measures. Despite favorable results from that particular resident
      group, the successful intervention did not spread practice-wide. Using this
      example, they detail the phases of evolution and lessons learned from their
      curriculum from 2006 to 2014 within a framework of previously published general
      principles for successful QI education, including those of exemplary care and
      learning sites. Successful programs require leadership, faculty expertise and
      mentorship, data management, learner buy-in, and patient engagement. Their
      experience will hopefully be of help to others as they attempt to simultaneously
      improve care and education. Further research and innovation are needed in this
      area, including optimizing strategies for strengthening resident-driven projects
      through partnership with nursing, allied health, and longitudinally engaged
      faculty members. 

PMID- 25054420
TI  - What aspects of letters of recommendation predict performance in medical school?
      Findings from one institution.
AB  - PURPOSE: To study medical students' letters of recommendation (LORs) from their
      applications to medical school to determine whether these predicted medical
      school performance, because many researchers have questioned LORs' predictive
      validity. METHOD: A retrospective cohort study of three consecutive graduating
      classes (2007-2009) at the Uniformed Services University of the Health Sciences
      was performed. In each class, the 27 students who had been elected into the Alpha
      Omega Alpha (AOA) Honor Medical Society were defined as top graduates, and the 27
      students with the lowest cumulative grade point average (GPA) were designated as
      "bottom of the class" graduates. For each student, the first three LORs (if
      available) in the application packet were independently coded by two blinded
      investigators using a comprehensive list of 76 characteristics. Each
      characteristic was compared with graduation status (top or bottom of the class),
      and those with statistical significance related to graduation status were
      inserted into a logistic regression model, with undergraduate GPA and Medical
      College Admission Test score included as control variables. RESULTS: Four hundred
      thirty-seven LORs were included. Of 76 LOR characteristics, 7 were associated
      with graduation status (P <= .05), and 3 remained significant in the regression
      model. Being rated as "the best" among peers and having an employer or supervisor
      as the LOR author were associated with induction into AOA, whereas having
      nonpositive comments was associated with bottom of the class students.
      CONCLUSIONS: LORs have limited value to admission committees, as very few LOR
      characteristics predict how students perform during medical school.

PMID- 25054421
TI  - A community-engaged cardiovascular health disparities research training
      curriculum: implementation and preliminary outcomes.
AB  - To overcome cardiovascular disease (CVD) disparities impacting high-risk
      populations, it is critical to train researchers and leaders in conducting
      community-engaged CVD disparities research. The authors summarize the key
      elements, implementation, and preliminary outcomes of the CVD Disparities
      Fellowship and Summer Internship Programs at the Johns Hopkins University Schools
      of Medicine, Nursing, and Bloomberg School of Public Health. In 2010, program
      faculty and coordinators established a transdisciplinary CVD disparities training
      and career development fellowship program for scientific investigators who desire
      to conduct community-engaged clinical and translational disparities research. The
      program was developed to enhance mentorship support and research training for
      faculty, postdoctoral fellows, and predoctoral students interested in conducting
      CVD disparities research. A CVD Disparities Summer Internship Program for
      undergraduate and preprofessional students was also created to provide a broad
      experience in public health and health disparities in Baltimore, Maryland, with a
      focus on CVD. Since 2010, 39 predoctoral, postdoctoral, and faculty fellows have
      completed the program. Participating fellows have published disparities-related
      research and given presentations both nationally and internationally. Five
      research grant awards have been received by faculty fellows. Eight
      undergraduates, one postbaccalaureate, and two medical professional students
      representing seven universities have participated in the summer undergraduate
      internship. Over half of the undergraduate students are applying to or have been
      accepted into medical or graduate school. The tailored CVD health disparities
      training curriculum has been successful at equipping varying levels of trainees
      (from undergraduate students to faculty) with clinical research and public health
      expertise to conducting community-engaged CVD disparities research.

PMID- 25054422
TI  - The influence of labor market changes on first-time medical school applicant
      pools.
AB  - PURPOSE: To explore whether the number and composition of first-time applicants
      to U.S. MD-granting medical schools, which have fluctuated over the past 30
      years, are related to changes in labor market strength, specifically the
      unemployment rate and wages. METHOD: The authors merged time series data from
      1980 through 2010 (inclusive) from five sources and used multivariate time series
      models to determine whether changes in labor market strength (and several other
      macro-level factors) were related to the number of the medical school applicants
      as reported by the American Medical College Application Service. Analyses were
      replicated across specific sex and race/ethnicity applicant pools. RESULTS: Two
      results surfaced in the analyses. First, the strength of the labor market was not
      influential in explaining changes in applicant pool sizes for all applicants, but
      was strongly influential in explaining changes for black and Hispanic males.
      Increases of $1,000 in prevailing median wages produced a 1.6% decrease in the
      white male applicant pool, while 1% increases in the unemployment rate were
      associated with 4.5% and 3.1% increases in, respectively, the black and Hispanic
      male applicant pools. Second, labor market strength was a more important
      determinant in applications from males than in applications from females.
      CONCLUSIONS: Although stakeholders cannot directly influence the overall economic
      market, they can plan and prepare for fewer applications from males, especially
      those who are black and Hispanic, when the labor market is strong.

PMID- 25054423
TI  - Reframing medical education to support professional identity formation.
AB  - Teaching medical professionalism is a fundamental component of medical education.
      The objective is to ensure that students understand the nature of professionalism
      and its obligations and internalize the value system of the medical profession.
      The recent emergence of interest in the medical literature on professional
      identity formation gives reason to reexamine this objective. The unstated aim of
      teaching professionalism has been to ensure the development of practitioners who
      possess a professional identity. The teaching of medical professionalism
      therefore represents a means to an end.The principles of identity formation that
      have been articulated in educational psychology and other fields have recently
      been used to examine the process through which physicians acquire their
      professional identities. Socialization-with its complex networks of social
      interaction, role models and mentors, experiential learning, and explicit and
      tacit knowledge acquisition-influences each learner, causing them to gradually
      "think, act, and feel like a physician."The authors propose that a principal goal
      of medical education be the development of a professional identity and that
      educational strategies be developed to support this new objective. The explicit
      teaching of professionalism and emphasis on professional behaviors will remain
      important. However, expanding knowledge of identity formation in medicine and of
      socialization in the medical environment should lend greater logic and clarity to
      the educational activities devoted to ensuring that the medical practitioners of
      the future will possess and demonstrate the qualities of the "good physician."

PMID- 25054424
TI  - Why some plant species are rare.
AB  - Biodiversity, including plant species diversity, is threatened worldwide as a
      result of anthropogenic pressures such as an increase of pollutants and climate
      change. Rare species in particular are on the verge of becoming extinct. It is
      still unclear as to why some plant species are rare and others are not. Are they
      rare due to: intrinsic reasons, dispersal capacity, the effects of management or
      abiotic circumstances? Habitat preference of rare plant species may play an
      important role in determining why some species are rare. Based on an extensive
      data set of soil parameters we investigated if rarity is due to a narrow habitat
      preference for abiotic soil parameters. For 23 different abiotic soil parameters,
      of which the most influential were groundwater-table, soil-pH and nutrient
      contents, we estimated species responses for common and rare species. Based on
      the responses per species we calculated the range of occurrence, the range
      between the 5 and 95 percentile of the response curve giving the habitat
      preference. Subsequently, we calculated the average response range for common and
      rare species. In addition, we designed a new graphic in order to provide a better
      means for presentation of the results. The habitat preferences of rare species
      for abiotic soil conditions are significantly narrower than for common species.
      Twenty of the twenty-three abiotic parameters showed on average significantly
      narrower habitat preferences for rare species than for common species; none of
      the abiotic parameters showed on average a narrower habitat preference for common
      species. The results have major implications for the conservation of rare plant
      species; accordingly management and nature development should be focussed on the
      maintenance and creation of a broad range of environmental conditions, so that
      the requirements of rare species are met. The conservation of (abiotic) gradients
      within ecosystems is particularly important for preserving rare species. 

PMID- 25054425
TI  - Thermally activated delayed fluorescence (TADF) and enhancing photoluminescence
      quantum yields of [Cu(I)(diimine)(diphosphine)](+) complexes-photophysical,
      structural, and computational studies.
AB  - The complexes [Cu(I)(POP)(dmbpy)][BF4] (1) and [Cu(I)(POP)(tmbpy)][BF4] (2)
      (dmbpy = 4,4'-dimethyl-2,2'-bipyridyl; tmbpy = 4,4',6,6'-tetramethyl-2,2'
      bipyridyl; POP = bis[2-(diphenylphosphino)-phenyl]ether) have been studied in a
      wide temperature range by steady-state and time-resolved emission spectroscopy in
      fluid solution, frozen solution, and as solid powders. Emission quantum yields of
      up to 74% were observed for 2 in a rigid matrix (powder), substantially higher
      than for 1 of around 9% under the same conditions. Importantly, it was found that
      the emission of 2 at ambient temperature represents a thermally activated delayed
      fluorescence (TADF) which renders the compound to be a good candidate for singlet
      harvesting in OLEDs. The role of steric constraints within the complexes, in
      particular their influences on the emission quantum yields, were investigated by
      hybrid-DFT calculations for the excited triplet state of 1 and 2 while
      manipulating the torsion angle between the bipyridyl and POP ligands. Both
      complexes showed similar flexibility within a +/-10 degrees  range of the torsion
      angle; however, 2 appeared limited to this range, whereas 1 could be further
      twisted with little energy demand. It is concluded that a restricted flexibility
      leads to a reduction of nonradiative deactivation and thus an increase of
      emission quantum yield. 

PMID- 25054426
TI  - Finite element analysis of masticatory stress on neoformed bone tissue after
      distraction osteogenesis and low-level laser therapy: a pilot study.
AB  - OBJECTIVE: This study aimed to understand the action of masticatory forces on an
      implant virtually introduced into the sheep mandible after distraction
      osteogenesis and low-level laser therapy (LLLT) by using finite element analysis.
      BACKGROUND DATA: Distraction osteogenesis as an alternative for bone
      reconstruction that may be used in the treatment of deformities. METHODS: Four
      ewes underwent distraction osteogenis to elongate the left mandibular body by 15
      m, and three of them underwent LLLT with the purpose of improving bone
      properties. After death, animals were scanned by computed tomography and their
      mandibles were tridimensionally reconstructed by computer programs. The physical
      properties related to hardness and modulus of elasticity of each animal were
      obtained from the dissected mandibles, and data were transferred to Femap
      software for finite element analysis. RESULTS: Animals exposed and not exposed to
      LLLT irradiation showed remarkably similar values for superficial hardness and
      modulus of elasticity, without statistically significant difference (p>0.05),
      between the values observed for the cortical bone and the cancellous bone among
      the groups. The neoformed mandible, after a brief period for bone healing, was
      able to promote stability for implant placement and proper distribution of
      masticatory forces. CONCLUSIONS: An implant introduced virtually into the site of
      bone neoformation did not suffer any micromotions relevant to osteointegration.
      Furthermore, finite element analysis showed that the neoformed portion of the
      mandible was able to absorb and distribute masticatory forces throughout its
      structure, even after a brief period for bone maturation.

PMID- 25054427
TI  - Railway embankments as new habitat for pollinators in an agricultural landscape.
AB  - Pollinating insect populations, essential for maintaining wild plant diversity
      and agricultural productivity, rely on (semi)natural habitats. An increasing
      human population is encroaching upon and deteriorating pollinator habitats. Thus
      the population persistence of pollinating insects and their associated ecosystem
      services may depend upon on man-made novel habitats; however, their importance
      for ecosystem services is barely understood. We tested if man-made infrastructure
      (railway embankments) in an agricultural landscape establishes novel habitats
      that support large populations of pollinators (bees, butterflies, hoverflies)
      when compared to typical habitats for these insects, i.e., semi-natural
      grasslands. We also identified key environmental factors affecting the species
      richness and abundance of pollinators on embankments. Species richness and
      abundance of bees and butterflies were higher for railway embankments than for
      grasslands. The occurrence of bare (non-vegetated) ground on embankments
      positively affected bee species richness and abundance, but negatively affected
      butterfly populations. Species richness and abundance of butterflies positively
      depended on species richness of native plants on embankments, whereas bee species
      richness was positively affected by species richness of non-native flowering
      plants. The density of shrubs on embankments negatively affected the number of
      bee species and their abundance. Bee and hoverfly species richness were
      positively related to wood cover in a landscape surrounding embankments. This is
      the first study showing that railway embankments constitute valuable habitat for
      the conservation of pollinators in farmland. Specific conservation strategies
      involving embankments should focus on preventing habitat deterioration due to
      encroachment of dense shrubs and maintaining grassland vegetation with patches of
      bare ground. 

PMID- 25054428
TI  - Poly(NaSS) functionalization modulates the conformation of fibronectin and
      collagen type I to enhance osteoblastic cell attachment onto Ti6Al4V.
AB  - Functionalization of surfaces with poly(sodium styrenesulfonate) (poly(NaSS)) has
      recently been found to enhance osteointegration of implantable materials. Radical
      polymerization of poly(NaSS) on titanium (Ti)-based substrates has been used to
      improve their long-term performance by preventing fibrosis and consequently
      implant loosening. However, the influence of the sulfonate groups on the early
      cell behavior and the associated molecular phenomena remains to be understood. In
      this work, we used quartz crystal microbalance with dissipation (QCM-D) to
      elucidate the role of poly(NaSS) in enhancing osteoblastic cell attachment. This
      was measured by following the cell attachment using the MC3T3-E1 cell line, on
      fetal bovine serum (FBS) preadsorbed surfaces and on substrates adsorbed with a
      series of relevant proteins, bovine serum albumin (BSA), fibronectin (Fn), and
      collagen type I (Col I). Comparison of the performance of poly(NaSS) with other
      clinically important substrates such as Ti alloy Ti6Al4V, gold, and poly(desamino
      tyrosyl-tyrosine ethyl ester carbonate) (poly(DTEc)) indicates poly(NaSS) to be a
      superior substrate for MC3T3-E1 cells attachment. This attachment was found to be
      integrin mediated in the presence of Fn and Col I. Antibodies specific to the RGD
      peptide and the N- and C-terminal HB-binding domains reacted more intensively
      with Fn adsorbed on poly(NaSS). Fn adapts a conformation favorable to RGD
      mediated cell attachment when adsorbed onto poly(NaSS). 

PMID- 25054429
TI  - Bacteria hold their breath upon surface contact as shown in a strain of
      Escherichia coli, using dispersed surfaces and flow cytometry analysis.
AB  - Bacteria are ubiquitously distributed throughout our planet, mainly in the form
      of adherent communities in which cells exhibit specific traits. The mechanisms
      underpinning the physiological shift in surface-attached bacteria are complex,
      multifactorial and still partially unclear. Here we address the question of the
      existence of early surface sensing through implementation of a functional
      response to initial surface contact. For this purpose, we developed a new
      experimental approach enabling simultaneous monitoring of free-floating,
      aggregated and adherent cells via the use of dispersed surfaces as adhesive
      substrates and flow cytometry analysis. With this system, we analyzed, in
      parallel, the constitutively expressed GFP content of the cells and production of
      a respiration probe--a fluorescent reduced tetrazolium ion. In an Escherichia
      coli strain constitutively expressing curli, a major E. coli adhesin, we found
      that single cell surface contact induced a decrease in the cell respiration level
      compared to free-floating single cells present in the same sample. Moreover, we
      show here that cell surface contact with an artificial surface and with another
      cell caused reduction in respiration. We confirm the existence of a bacterial
      cell "sense of touch" ensuring early signalling of surface contact formation
      through respiration down modulation.

PMID- 25054430
TI  - Differentiating drug-induced multichannel block on the electrocardiogram:
      randomized study of dofetilide, quinidine, ranolazine, and verapamil.
AB  - Block of the hERG potassium channel and prolongation of the QT interval are
      predictors of drug-induced torsade de pointes. However, drugs that block the hERG
      potassium channel may also block other channels that mitigate torsade risk. We
      hypothesized that the electrocardiogram can differentiate the effects of
      multichannel drug block by separate analysis of early repolarization (global J
      Tpeak) and late repolarization (global Tpeak-Tend). In this prospective
      randomized controlled clinical trial, 22 subjects received a pure hERG potassium
      channel blocker (dofetilide) and three drugs that block hERG and either calcium
      or late sodium currents (quinidine, ranolazine, and verapamil). The results show
      that hERG potassium channel block equally prolongs early and late repolarization,
      whereas additional inward current block (calcium or late sodium) preferentially
      shortens early repolarization. Characterization of multichannel drug effects on
      human cardiac repolarization is possible and may improve the utility of the
      electrocardiogram in the assessment of drug-related cardiac electrophysiology. 

PMID- 25054432
TI  - Stereodefined acyclic trisubstituted metal enolates towards the asymmetric
      formation of quaternary carbon stereocentres.
AB  - Reactions that involve metal enolate species are amongst the most versatile
      carbon-carbon bond forming processes available to synthetic chemists. Enolate
      species are involved in a multitude of powerful applications in asymmetric
      organic synthesis, but the generation of fully substituted enolates in a
      geometrically defined form is not easily achieved especially in acyclic systems.
      In this Feature Article we focus on the most prominent examples reported in the
      literature describing the formation of highly diastereo- and enantiomerically
      enriched quaternary stereocentres in acyclic molecules derived from stereodefined
      non-cyclic trisubstituted metal enolates. 

PMID- 25054431
TI  - Inflammation-related genetic variants predict toxicity following definitive
      radiotherapy for lung cancer.
AB  - Definitive radiotherapy improves locoregional control and survival in inoperable
      non-small cell lung cancer patients. However, radiation-induced toxicities
      (pneumonitis/esophagitis) are common dose-limiting inflammatory conditions. We
      therefore conducted a pathway-based analysis to identify inflammation-related
      single-nucleotide polymorphisms associated with radiation-induced pneumonitis or
      esophagitis. A total of 11,930 single-nucleotide polymorphisms were genotyped in
      201 stage I-III non-small cell lung cancer patients treated with definitive
      radiotherapy. Validation was performed in an additional 220 non-small cell lung
      cancer cases. After validation, 19 single-nucleotide polymorphisms remained
      significant. A polygenic risk score was generated to summarize the effect from
      validated single-nucleotide polymorphisms. Significant improvements in
      discriminative ability were observed when the polygenic risk score was added into
      the clinical/epidemiological variable-based model. We then used 277
      lymphoblastoid cell lines to assess radiation sensitivity and expression
      quantitative trait loci (eQTL) relationships of the identified single-nucleotide
      polymorphisms. Three genes (PRKCE, DDX58, and TNFSF7) were associated with
      radiation sensitivity. We concluded that inflammation-related genetic variants
      could contribute to the development of radiation-induced toxicities. 

PMID- 25054433
TI  - SELDI-TOF-MS proteomic profiling of serum, urine, and amniotic fluid in neural
      tube defects.
AB  - Neural tube defects (NTDs) are common birth defects, whose specific biomarkers
      are needed. The purpose of this pilot study is to determine whether protein
      profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS.
      ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78
      urine samples and 76 amniotic fluid samples. The validity of classification tree
      was then challenged with a blind test set including another 20 NTD-mothers and 18
      controls in serum samples, and another 19 NTD-mothers and 17 controls in urine
      samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples.
      Eight proteins detected in serum samples were up-regulated and four proteins were
      down-regulated in the NTD group. Four proteins detected in urine samples were up
      regulated and one protein was down-regulated in the NTD group. Six proteins
      detected in amniotic fluid samples were up-regulated and one protein was down
      regulated in the NTD group. The classification tree for serum samples separated
      NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity
      of 97% in the training set, and achieving a sensitivity of 90% and a specificity
      of 97% and a positive predictive value of 95% in the test set. The classification
      tree for urine samples separated NTDs from controls, achieving a sensitivity of
      95% and a specificity of 94% in the training set, and achieving a sensitivity of
      89% and a specificity of 82% and a positive predictive value of 85% in the test
      set. The classification tree for amniotic fluid samples separated NTDs from
      controls, achieving a sensitivity of 93% and a specificity of 89% in the training
      set, and achieving a sensitivity of 90% and a specificity of 88% and a positive
      predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an
      additional method for NTDs pregnancies detection. 

PMID- 25054434
TI  - Nanoscale integration of two-dimensional materials by lateral heteroepitaxy.
AB  - Materials integration in heterostructures with novel properties different from
      those of the constituents has become one of the most powerful concepts of modern
      materials science. Two-dimensional (2D) crystals represent a new class of
      materials from which such engineered structures can be envisioned. Calculations
      have predicted emergent properties in 2D heterostructures with nanoscale feature
      sizes, but methods for their controlled fabrication have been lacking. Here, we
      use sequential graphene and boron nitride growth on Ru(0001) to show that lateral
      heteroepitaxy, the joining of 2D materials by preferential incorporation of
      different atomic species into exposed 1D edges during chemical vapor deposition
      on a metal substrate, can be used for the bottom-up synthesis of 2D
      heterostructures with characteristic dimensions on the nanoscale. Our results
      suggest that on a proper substrate, this method lends itself to building
      nanoheterostructures from a wide range of 2D materials. 

PMID- 25054435
TI  - Abnormal Sensitivity to Glucagon and Related Peptides in Primary Adrenal
      Cushing's Syndrome.
AB  - Illegitimate G-protein coupled receptors are known to control cortisol secretion
      in adrenal adenomas and bilateral macronodular adrenal hyperplasias (BMAHs)
      causing Cushing's syndrome. In the present study, we have evaluated the role of
      glucagon in the regulation of cortisol secretion in 13 patients with BMAH or
      adrenocortical adenoma causing subclinical or overt Cushing's syndrome. Injection
      of glucagon provoked an increase in plasma cortisol in 2 patients. After surgery,
      immunohistochemical studies showed the presence of glucagon receptor-like
      immunoreactivity in clusters of spongiocytic cells in adrenal tissues from
      patients who were sensitive in vivo to glucagon. We also observed an in vitro
      cortisol response to vasoactive intestinal peptide from an adenoma, which was
      insensitive to glucagon and pituitary adenylate cyclase-activating peptide.
      Altogether, our data show that ectopic glucagon receptors are expressed in some
      adrenal cortisol-producing benign lesions. Our results also indicate that
      circulating glucagon may influence cortisol release under fasting conditions. 

PMID- 25054436
TI  - Efficacy and safety of colesevelam in combination with pioglitazone in patients
      with type 2 diabetes mellitus.
AB  - Colesevelam improves glycemic control in patients with type 2 diabetes when added
      to existing metformin-, sulfonylurea-, or insulin-based regimens. We evaluated
      colesevelam's effects in subjects on stable pioglitazone-based therapy. This 24
      week multicenter, double-blind, randomized, placebo-controlled study enrolled
      adults with type 2 diabetes who had suboptimal glycemic control [HbA1c >= 58
      mmol/mol (7.5%) and <= 80 mmol/mol (9.5%)] on pioglitazone (30 or 45 mg) with or
      without 1-2 other oral antidiabetes medications. Subjects were randomized to
      colesevelam 3.8 g/day (n = 280) or placebo (n = 282) added to existing
      pioglitazone-based therapy. Primary efficacy variable was mean change in HbA1c
      from baseline to Week 24. Secondary variables included safety and tolerability,
      fasting plasma glucose changes, glycemic responses, and lipid profile. Tertiary
      variables included lipid particle profile changes by nuclear magnetic resonance.
      Colesevelam decreased HbA1c [least-squares mean treatment difference, - 3.5
      mmol/mol (- 0.32%); p < 0.001] and fasting plasma glucose (- 14.7 mg/dl; p<0.001)
      vs. placebo at Week 24. More subjects receiving colesevelam vs. placebo achieved
      HbA1c reduction >= 7.7 mmol/mol (0.7%) (40% vs. 25%; p<0.001) or HbA1c < 53
      mmol/mol (7.0%) (21% vs. 13%; p = 0.012). Colesevelam also decreased total
      cholesterol (mean treatment difference, - 6.5%), LDL-cholesterol (- 16.4%), non
      HDL-cholesterol (- 9.8%), apolipoprotein B (- 8.8%), and total LDL particle
      concentration, and increased apolipoprotein A1 (+3.4%) and triglycerides (median
      treatment difference, + 11.3%) vs. placebo (all p < 0.001). There were no serious
      drug-related adverse events, and the majority of adverse events were mild or
      moderate. In subjects with type 2 diabetes inadequately controlled with
      pioglitazone-based therapy, add-on colesevelam therapy improved glycemic control
      and lipid parameters and was well tolerated. ClinicalTrials.gov identifier:
      NCT00789750.

PMID- 25054437
TI  - Real-time monitoring of GPCR/cAMP signalling by FRET and single-molecule
      microscopy.
AB  - G-protein-coupled receptors (GPCRs), located on the surface of virtually every
      cell in our organism, mediate the effects of many hormones and neurotransmitters.
      Although GPCRs have been extensively studied for more than 4 decades using
      pharmacological and biochemical methods, the recent introduction of optical
      methods such as fluorescence resonance energy transfer (FRET) and single-molecule
      microscopy is fostering novel and important discoveries in the field. Here, we
      review the use of such optical methods, focusing on some recent examples of their
      application to important and still unresolved questions concerning the spatial
      organisation and dynamics of GPCR signalling. 

PMID- 25054438
TI  - 13th Annual Meeting of the Safety Pharmacology Society: focus on novel
      technologies and safety pharmacology frontiers.
AB  - INTRODUCTION: The 13th Annual Meeting of the Safety Pharmacology (SP) Society
      discussed novel therapeutic areas, recent regulatory developments, emerging
      biology technologies and non-pharmaceutical dairy products that may need SP
      evaluations for ensuring their human safety. AREAS COVERED: The meeting honored
      Willem Einthoven, the father of electrocardiography. The Comprehensive in vitro
      Proarrhythmia Assay (CiPA) is an under-discussion proposal for replacing the
      International Conference on Hamonization (ICH) S7B guideline strategy. Drugs
      targeting epigenetic mechanisms (e.g., histone deacetylase inhibitors) have the
      potential to produce proarrhythmic safety liabilities by dysregulating the
      synthesis of cardiac ion channel proteins as well as the intracellular machinery,
      moving them to sarcolemmal residence. Novel frontiers of regulatory SP
      investigations are functional food and probiotic (microorganisms) preparations.
      EXPERT OPINION: The CiPA initiative is a unique opportunity for concerned
      stakeholders to drive SP into the adoption of 21st century safety assessment
      platforms, which, for discovering and mitigating mechanisms conferring safety
      risks to drugs, apply chiefly in silico and in vitro rather than traditional in
      vivo pharmacodynamics assays. The SP evaluation of functional foods and
      probiotics needs the development of product-tailored investigational approaches.

PMID- 25054439
TI  - Realized volatility and absolute return volatility: a comparison indicating
      market risk.
AB  - Measuring volatility in financial markets is a primary challenge in the theory
      and practice of risk management and is essential when developing investment
      strategies. Although the vast literature on the topic describes many different
      models, two nonparametric measurements have emerged and received wide use over
      the past decade: realized volatility and absolute return volatility. The former
      is strongly favored in the financial sector and the latter by econophysicists. We
      examine the memory and clustering features of these two methods and find that
      both enable strong predictions. We compare the two in detail and find that
      although realized volatility has a better short-term effect that allows
      predictions of near-future market behavior, absolute return volatility is easier
      to calculate and, as a risk indicator, has approximately the same sensitivity as
      realized volatility. Our detailed empirical analysis yields valuable guidelines
      for both researchers and market participants because it provides a significantly
      clearer comparison of the strengths and weaknesses of the two methods. 

PMID- 25054440
TI  - Road traffic deaths and injuries are under-reported in Ethiopia: a capture
      recapture method.
AB  - In low and middle income countries road traffic injuries are commonly under
      reported. This problem is significantly higher among those less severely injured
      road users. The objective of this study was to determine the incidence and the
      level of ascertainment of road traffic injuries and deaths by traffic police and
      hospital registry. In this study two-sample capture-recapture method was applied
      using data from traffic police and hospital injury surveillance, through June
      2012 to May 2013. The study was conducted on one of the busiest highways in
      Ethiopia, the Addis Ababa - Hawassa highway. Primary data were collected by
      accident investigators and hospital emergency nurses using a structured
      checklist. Four matching variables; name of the victim, sex, place and time of
      the accidents was used to get the matched cases. During the study period the
      police independently reported 224 deaths and 446 injuries/billion vehicle
      kilometer while hospitals reported 123 deaths and 1,046 injuries/billion vehicle
      kilometer. Both sources in common captured 73 deaths and 248 injuries/billion
      vehicle kilometer. Taking the two data sources into consideration, the capture
      recapture model estimated the incidence of deaths and injuries ranged 368-390 and
      1,869-1,895 per billion vehicle kilometer, respectively. The police source
      captured 57.4%-60.9% of deaths and 23.5%-23.9% of injuries while the hospital
      sources captured 31.5%-33.4% of deaths and 55.2%-56% of injuries. Deaths and
      injuries among females, younger age victims, cyclists/motorcyclists and
      pedestrians were under-reported by traffic police. In conclusion neither of the
      two sources independently provided accurate coverage of road traffic incident
      related deaths and injuries. Strengthening both systems is necessary to obtain
      accurate information on road accidents and human causalities.

PMID- 25054441
TI  - Mycobacterium mucogenicum infection following dacryocystorhinostomy and Crawford
      tube placement.
AB  - IMPORTANCE: Nontuberculous mycobacterial infections of the skin can be seen in
      cases of immunosuppression and/or traumatic implantation of contaminated objects.
      Surgical settings with appropriate sterilization techniques have been immune to
      these types of infections. We report a case of nosocomially derived infection
      from a sterile procedure. OBSERVATIONS: A woman in her 70s presented with a
      facial lesion after an ophthalmologic procedure that was discovered to be a
      nontuberculous mycobacterial infection. It was successfully treated with oral
      antibiotics. CONCLUSIONS AND RELEVANCE: Nontuberculous mycobacterial infections
      should be considered in the differential diagnosis of new lesions arising after
      invasive procedures, even in immunocompetent patients in seemingly sterile
      settings.

PMID- 25054442
TI  - A combinatorial approach to biophysically characterise chemokine-glycan binding
      affinities for drug development.
AB  - Chemokine binding to glycosaminoglycans (GAGs) is recognised to be an important
      step in inflammation and other pathological disorders like tumor growth and
      metastasis. Although different ways and strategies to interfere with these
      interactions are being pursued, no major breakthrough in the development of
      glycan-targeting drugs has been reported so far. We have engineered CXCL8 towards
      a dominant-negative form of this chemokine (dnCXCL8) which was shown to be highly
      active in various inflammatory animal models due to its inability to
      bind/activate the cognate CXCL8 GPC receptors on neutrophils in combination with
      its significantly increased GAG-binding affinity [1]. For the development of GAG
      targeting chemokine-based biopharmaceuticals, we have established a repertoire of
      methods which allow the quantification of protein-GAG interactions. Isothermal
      fluorescence titration (IFT), surface plasmon resonance (SPR), isothermal
      titration calorimetry (ITC), and a novel ELISA-like competition assay (ELICO)
      have been used to determine Kd and IC50 values for CXCL8 and dnCXCL8 interacting
      with heparin and heparan sulfate (HS), the proto-typical members of the GAG
      family. Although the different methods gave different absolute affinities for the
      four protein-ligand pairs, the relative increase in GAG-binding affinity of
      dnCXCL8 compared to the wild type chemokine was found by all methods. In
      combination, these biophysical methods allow to discriminate between unspecific
      and specific protein-GAG interactions. 

PMID- 25054443
TI  - Effects of Echium plantagineum L. bee pollen on basophil degranulation:
      relationship with metabolic profile.
AB  - This study aimed to evaluate the anti-allergic potential of Echium plantagineum
      L. bee pollen and to characterize its primary metabolites. The activity of E.
      plantagineum hydromethanolic extract, devoid of alkaloids, was tested against
      beta-hexosaminidase release in rat basophilic leukemic cells (RBL-2H3). Two
      different stimuli were used: calcium ionophore A23187 and IgE/antigen.
      Lipoxygenase inhibitory activity was evaluated in a cell-free system using
      soybean lipoxygenase. Additionally, the extract was analysed by HPLC-UV for
      organic acids and by GC-IT/MS for fatty acids. In RBL-2H3 cells stimulated either
      with calcium ionophore or IgE/antigen, the hydromethanolic extract significantly
      decreased beta-hexosaminidase release until the concentration of 2.08 mg/mL,
      without compromising cellular viability. No effect was found on lipoxygenase.
      Concerning extract composition, eight organic acids and five fatty acids were
      determined for the first time. Malonic acid (80%) and alpha-linolenic acid (27%)
      were the main compounds in each class. Overall, this study shows promising
      results, substantiating for the first time the utility of intake of E.
      plantagineum bee pollen to prevent allergy and ameliorate allergy symptoms,
      although a potentiation of an allergic response can occur, depending on the dose
      used. 

PMID- 25054444
TI  - A systematic review of the botanical, phytochemical and pharmacological profile
      of Dracaena cochinchinensis, a plant source of the ethnomedicine "dragon's
      blood".
AB  - "Dragon's blood" is the name given to a deep red resin obtained from a variety of
      plant sources. The resin extracted from stems of Dracaena cochinchinensis is one
      such source of "dragon's blood". It has a reputation for facilitating blood
      circulation and dispersing blood stasis. In traditional Chinese medicine, this
      resinous medicine is commonly prescribed to invigorate blood circulation for the
      treatment of traumatic injuries, blood stasis and pain. Modern pharmacological
      studies have found that this resinous medicine has anti-bacterial, anti
      spasmodic, anti-inflammatory, analgesic, anti-diabetic, and anti-tumor
      activities, while it is also known to enhance immune function, promote skin
      repair, stop bleeding and enhance blood circulation. Various compounds have been
      isolated from the plant, including loureirin A, loureirin B, loureirin C,
      cochinchinenin, socotrin-4'-ol, 4',7-dihydroxyflavan, 4-methylcholest-7-ene-3-ol,
      ethylparaben, resveratrol, and hydroxyphenol. The present review summarizes
      current knowledge concerning the botany, phytochemistry, pharmacological effects,
      toxicology studies and clinical applications of this resinous medicine as derived
      from D. cochinchinenesis. 

PMID- 25054446
TI  - Cervical cancer incidence in ontario women: differing sociodemographic gradients
      by morphologic type (adenocarcinoma versus squamous cell).
AB  - OBJECTIVE: Identify patterns in cervical cancer incidence in Ontario according to
      neighborhood sociodemographic characteristics over time and by morphologic type.
      METHODS: Incident cases of cervical cancer diagnosed from 1991 to 2009 were
      obtained from the Ontario Cancer Registry. Population data and data on
      neighborhood sociodemographic characteristics were obtained from the Canadian
      Census. Age-standardized incidence rates (ASIR) and rate ratios (RRs) with 95%
      confidence intervals (CIs) were calculated for each sociodemographic
      characteristic, stratified by morphologic type (squamous cell carcinoma and
      adenocarcinoma) and time period of diagnosis. RESULTS: Incidence was 51% higher
      in the poorest neighborhoods compared with the richest (RR, 1.51; 95% CI, 1.42
      1.61) and 7% higher in rural areas compared with urban (RR, 1.07; 95% CI, 1.01
      1.13). Incidence of squamous cell carcinoma was significantly higher in the
      poorest neighborhoods compared with the richest (RR, 1.74; 95% CI, 1.61-1.88), a
      trend observed for all time periods, and in rural areas compared with urban (RR,
      1.10; 95% CI, 1.02-1.18). For adenocarcinoma, ASIRs in the earlier time period
      (1991-1998) were higher in the poorest neighborhoods compared with richest (RR,
      1.26; 95% CI, 1.01-1.57), whereas for the more recent time period (1999-2009),
      ASIRs were lower for women living in the poorest neighborhoods compared with the
      richest (RR, 0.82; 95% CI, 0.68-0.99). CONCLUSIONS: This study identified
      significantly higher incidence of cervical cancer in low-income neighborhoods in
      Ontario. The association was especially pronounced for squamous cell carcinoma
      and varied by time period for adenocarcinoma. Improvements to screening and
      prevention efforts against oncogenic human papillomavirus strains would increase
      the detection of cervical cancer, adenocarcinoma especially, and may further
      reduce cervical cancer incidence.

PMID- 25054445
TI  - Effect of treatment delay on survival in patients with cervical cancer: a
      historical cohort study.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of treatment
      delay on prognosis in patients with cervical cancer. METHODS: The study group of
      this historic cohort study comprised 321 patients newly diagnosed with cervical
      cancer between 1999 and 2010. Time from diagnosis to treatment was analyzed both
      as a continuous variable and as a categorical variable in 3 groups that differed
      in waiting time between diagnosis and treatment initiation: 30 days or less
      (group 1, n = 134), 30 to 45 days (group 2, n = 86), and more than 45 days (group
      3, n = 101). Associations between waiting time group, patients' characteristics,
      and disease outcome were investigated using t tests, analyses of variance and Cox
      regression analyses, Kaplan-Meier survival analysis, and log-rank (Mantel-Cox)
      tests. RESULTS: Time from diagnosis to treatment initiation, when analyzed as a
      continuous variable, was not a significant factor in survival. There were no
      between-group differences in age, smoking rate, marital status, gravidity,
      parity, tumor histology, or lymph node involvement. Early-stage disease and small
      tumor diameter were diagnosed most frequently in group 3. However, there was no
      significant between-group difference in 3-year survival rates (74.6%, 82.2%, and
      80.8% in groups 1, 2, and 3, respectively; P = 0.38). On multivariate analysis,
      only stage, histology, and lymph node involvement were significant prognostic
      factors for survival. Before starting treatment, 28 patients underwent ovarian
      preservation procedures. CONCLUSIONS: Longer waiting time from diagnosis to
      treatment was not associated with worse survival. Our findings imply that if
      patients desire fertility or ovarian preservation procedures before starting
      treatment, it is acceptable to allow time for them.

PMID- 25054447
TI  - The role of HE4 in ovarian cancer follow-up: a review.
AB  - OBJECTIVE: The aim of this review was to analyze the state of the art about HE4
      and follow-up in patients treated for ovarian cancer. METHODS: A literature
      search was conducted in the MEDLINE database using the key words "HE4" and
      "ovarian cancer" and "recurrence" or "relapse" or "follow up." RESULTS: Seven of
      28 clinical studies were selected. Four studies were prospective, and all of them
      were based on a small number of patients (8-73 women). A failure of HE4 levels to
      normalize at completion of standard therapy may indicate a poor prognosis, thus
      suggesting the need of a closer follow-up. Moreover, HE4 showed better
      sensibility and specificity in the diagnosis of ovarian cancer recurrence with
      respect to CA-125, being also an earlier indicator of the relapse with a lead
      time of 5 to 8 months. HE4 showed a better performance in this setting if
      performed in association with other markers (CA-125, CA-72.4). HE4 seems to be an
      independent predictive factor for the surgical outcome at secondary cytoreductive
      surgery and to maintain its prognostic role even after the recurrence.
      CONCLUSIONS: These preliminary data start to suggest a superiority of HE4 over CA
      125 in the detection of ovarian cancer recurrence. Moreover, the prognostic role
      of HE4 could help clinicians to personalize the follow-up program, whereas its
      predictive role could be useful to plan the treatment of the relapse. The role of
      HE4 in ovarian cancer follow-up deserves to be further investigated in
      prospective randomized multicentric studies.

PMID- 25054448
TI  - Laparoscopic and open abdominal staging for early-stage ovarian cancer: our
      experience, systematic review, and meta-analysis of comparative studies.
AB  - OBJECTIVES: The aim of this study was to analyze perioperative and long-term
      survival outcomes after either laparoscopic or open abdominal staging for
      apparent early-stage ovarian cancer. METHODS: Data of consecutive women with
      early-stage ovarian cancer undergoing comprehensive laparoscopic staging between
      2003 and 2010 were matched with a historical cohort of patients undergoing open
      surgery. Five-year survival outcomes were analyzed using the Kaplan-Meier method.
      In addition, a systematic review of the literature and meta-analysis of
      comparative studies was performed RESULTS: A total of 35 women undergoing staging
      via laparoscopy were compared with a cohort of 32 patients undergoing open
      surgery. Baseline characteristics were similar between groups. Spillage occurred
      in 6 and 4 patients in laparoscopic and open group, respectively (P = 0.59).
      Patients undergoing laparoscopy experienced longer operative time (P < 0.001),
      shorter hospital stay (P = 0.03), and lower postoperative complication rate (3%
      vs 28%; P = 0.005) than patients undergoing staging via open surgery. The median
      (range) follow-up period was 64 (37-106) and 100 (61-278) months for case and
      control, respectively (P < 0.001). Five-year disease-free survival (P = 0.12, log
      rank test) and overall survival (P = 0.26, log-rank test) were not influenced by
      surgical approach. Pooled analyses of the literature results corroborate our
      results suggesting an improvement of perioperative results in the laparoscopic
      group in comparison with the open abdominal one. In comparison with open surgery,
      laparoscopy did not influenced spillage (odds ratio [OR], 0.78; 95% confidence
      interval [CI], 0.35-1.73) and upstaging rate (OR, 0.7; 95% CI, 0.38-1.27). No
      between-group differences in survival were observed (OR, 0.5; 95% CI, 0.21-1.21).
      CONCLUSIONS: Laparoscopy upholds open surgery in long-term oncologic control,
      reducing morbidity.

PMID- 25054450
TI  - Is minimal invasive surgery for primary and secondary debulking of
      ovarian/peritoneal/fallopian tube cancer going too far?

PMID- 25054449
TI  - Web-based recruiting for a survey on knowledge and awareness of cervical cancer
      prevention among young women living in Kanagawa prefecture, Japan.
AB  - OBJECTIVES: Cervical cancer (CC) incidence and mortality among young women have
      been increasing in Japan. To develop effective measures to combat this, we
      assessed the feasibility of using a social networking site (SNS) to recruit a
      representative sample of young women to conduct a knowledge and attitude study
      about CC prevention via an internet-based questionnaire. METHODS: From July 2012
      to March 2013, advertising banners targeting women aged 16 to 35 years in
      Kanagawa Prefecture were placed on Facebook in a similar manner as an Australian
      (AUS) study conducted in 16- to 25-year-olds in 2010 and on a homepage to
      advertise our CC advocacy activities. Eligible participants were emailed
      instructions for accessing our secure Web site where they completed an online
      survey including demographics, awareness, and knowledge of human papillomavirus
      (HPV) and CC. Data for the study population were compared with the general
      Japanese population and the AUS study. RESULTS: Among 394 women who expressed
      interest, 243 (62%) completed the survey, with 52% completing it via Facebook.
      Women aged 26 to 35 years, living in Yokohama City, with an education beyond high
      school, were overrepresented. Participants had high awareness and knowledge of
      HPV and CC, comparable with the AUS study participants. However, the self
      reported HPV vaccination rate (22% among participants aged 16-25 years) and the
      recognition rate of the link between smoking and CC (31%) were significantly
      lower than in the AUS study (58% and 43%, respectively) (P < 0.05). Significant
      predictors of high knowledge scores about HPV included awareness of HPV vaccine
      (P < 0.001) and self-reported HPV vaccination (P < 0.05). CONCLUSIONS: The SNS
      and homepage are efficient methods to recruit young women into health surveys,
      which can effectively be performed online. A nationwide survey using SNSs would
      be an appropriate next step to better understand the current lack of uptake of
      the national HPV vaccine program by young women in Japan.

PMID- 25054451
TI  - The role of metallothionein-3 in streptozotocin-induced beta-islet cell death and
      diabetes in mice.
AB  - Metallothionein-3 (Mt3), a zinc (Zn)-regulatory protein mainly expressed in the
      central nervous system, may contribute to oxidative cell death. In the present
      study, we examined the possible role of Mt3 in streptozotocin (STZ)-induced islet
      cell death and consequent hyperglycemia. Quantitative real-time polymerase chain
      reaction (RT-PCR) confirmed that islet cells expressed Mt3 mRNA. In all cases,
      wild-type (WT) mice injected with STZ exhibited hyperglycemia 7-21 days later. In
      stark contrast, all Mt3-null mice remained normoglycemic following STZ injection.
      STZ treatment increased free Zn levels in islet cells and induced their death in
      WT mice, but failed to do so in Mt3-null mice. Consistent with this, cultured Mt3
      null islet cells exhibited striking resistance to STZ toxicity. Notably, PDE3a
      (phosphodiesterase 3A) was downregulated in islets of Mt3-null mice compared to
      those of WT mice, and was not induced by STZ treatment. Moreover, the PDE3
      inhibitor cilostazol reduced islet cell death, likely by increasing cAMP levels,
      further supporting a role for PDE3 in STZ-induced islet cell death. Collectively,
      these results demonstrate that Mt3 may act through PDE3a to play a key role in Zn
      dyshomeostasis and cell death in STZ-treated islets. 

PMID- 25054452
TI  - Variable effects of 12 weeks of omega-3 supplementation on resting skeletal
      muscle metabolism.
AB  - Omega-3 supplementation has been purported to improve the function of several
      organs in the body, including reports of increased resting metabolic rate (RMR)
      and reliance on fat oxidation. However, the potential for omega-3s to modulate
      human skeletal muscle metabolism has received little attention. This study
      examined the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) supplementation on whole-body RMR and the content of proteins involved in
      fat metabolism in human skeletal muscle. Recreationally active males supplemented
      with 3.0 g/day of EPA and DHA (n = 21) or olive oil (n = 9) for 12 weeks. Resting
      muscle biopsies were sampled in a subset of 10 subjects before (pre) and after
      (post) omega-3 supplementation. RMR significantly increased (5.3%, p = 0.040)
      following omega-3 supplementation (Pre, 1.33 +/-0.05; Post, 1.40 +/-0.04
      kcal/min) with variable individual responses. When normalizing for body mass,
      this effect was lost (5.2%, p = 0.058). Omega-3s did not affect whole-body fat
      oxidation, and olive oil did not alter any parameter assessed. Omega-3
      supplementation did not affect whole muscle, sarcolemmal, or mitochondrial
      FAT/CD36, FABPpm, FATP1 or FATP4 contents or mitochondrial electron chain and PDH
      proteins, but did increase the long form of UCP3 by 11%. In conclusion,
      supplementation with a high dose of omega-3s for 12 weeks increased RMR in a
      small and variable manner in a group of healthy young men. Omega-3
      supplementation also had no effect on several proteins involved in skeletal
      muscle fat metabolism and did not cause mitochondrial biogenesis. 

PMID- 25054453
TI  - First principle chemical kinetics in zeolites: the methanol-to-olefin process as
      a case study.
AB  - To optimally design next generation catalysts a thorough understanding of the
      chemical phenomena at the molecular scale is a prerequisite. Apart from
      qualitative knowledge on the reaction mechanism, it is also essential to be able
      to predict accurate rate constants. Molecular modeling has become a ubiquitous
      tool within the field of heterogeneous catalysis. Herein, we review current
      computational procedures to determine chemical kinetics from first principles,
      thus by using no experimental input and by modeling the catalyst and reacting
      species at the molecular level. Therefore, we use the methanol-to-olefin (MTO)
      process as a case study to illustrate the various theoretical concepts. This
      process is a showcase example where rational design of the catalyst was for a
      long time performed on the basis of trial and error, due to insufficient
      knowledge of the mechanism. For theoreticians the MTO process is particularly
      challenging as the catalyst has an inherent supramolecular nature, for which not
      only the Bronsted acidic site is important but also organic species, trapped in
      the zeolite pores, must be essentially present during active catalyst operation.
      All these aspects give rise to specific challenges for theoretical modeling. It
      is shown that present computational techniques have matured to a level where
      accurate enthalpy barriers and rate constants can be predicted for reactions
      occurring at a single active site. The comparison with experimental data such as
      apparent kinetic data for well-defined elementary reactions has become feasible
      as current computational techniques also allow predicting adsorption enthalpies
      with reasonable accuracy. Real catalysts are truly heterogeneous in a space- and
      time-like manner. Future theory developments should focus on extending our view
      towards phenomena occurring at longer length and time scales and integrating
      information from various scales towards a unified understanding of the catalyst.
      Within this respect molecular dynamics methods complemented with additional
      techniques to simulate rare events are now gradually making their entrance within
      zeolite catalysis. Recent applications have already given a flavor of the benefit
      of such techniques to simulate chemical reactions in complex molecular
      environments. 

PMID- 25054456
TI  - X-linked juvenile retinoschisis in a consanguineous family: phenotypic
      variability and report of a homozygous female patient.
AB  - PURPOSE: To describe the phenotypic variability in a consanguineous family with
      genetically confirmed X-linked retinoschisis. METHODS: Five patients, including
      one homozygous female, were characterized by clinical examination, optical
      coherence tomography, fundus autofluorescence, mapping of macular pigment optical
      density, electroretinography, and DNA testing. RESULTS: The 36-year-old male
      index patient showed a ring of enhanced autofluorescence and outer retinal
      atrophy on optical coherence tomography. Electroretinography testing revealed a
      reduced a/b ratio. His mother presented with a central atrophic retina with
      markedly reduced autofluorescence signal and a surrounding ring of enhanced
      autofluorescence. The 40-year-old brother of the index patient and his 2 sons
      showed characteristic signs for X-linked retinoschisis, including retinal schisis
      and a reduced a/b ratio. Genetic testing revealed a c.293C>A mutation in the RS1
      gene in all affected family members while the mother of the index patient was
      homozygous for this mutation. CONCLUSION: X-linked retinoschisis can present with
      a wide phenotypic variability. Here, detailed family history and genetic testing
      established the diagnosis of X-linked retinoschisis despite striking differences
      in phenotypic presentation in affected subjects, homozygosity of one affected
      female, and seemingly dominant inheritance in three subsequent generations
      because of multiple consanguinity.

PMID- 25054455
TI  - Integrative "omic" analysis of experimental bacteremia identifies a metabolic
      signature that distinguishes human sepsis from systemic inflammatory response
      syndromes.
AB  - RATIONALE: Sepsis is a leading cause of morbidity and mortality. Currently, early
      diagnosis and the progression of the disease are difficult to make. The
      integration of metabolomic and transcriptomic data in a primate model of sepsis
      may provide a novel molecular signature of clinical sepsis. OBJECTIVES: To
      develop a biomarker panel to characterize sepsis in primates and ascertain its
      relevance to early diagnosis and progression of human sepsis. METHODS:
      Intravenous inoculation of Macaca fascicularis with Escherichia coli produced
      mild to severe sepsis, lung injury, and death. Plasma samples were obtained
      before and after 1, 3, and 5 days of E. coli challenge and at the time of
      killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An
      integrative analysis of the metabolomic and transcriptomic datasets was performed
      to identify a panel of sepsis biomarkers. MEASUREMENTS AND MAIN RESULTS: The
      extent of E. coli invasion, respiratory distress, lethargy, and mortality was
      dependent on the bacterial dose. Metabolomic and transcriptomic changes
      characterized severe infections and death, and indicated impaired mitochondrial,
      peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and
      plasma metabolome suggested impaired fatty acid catabolism regulated by
      peroxisome-proliferator activated receptor signaling. A representative four
      metabolite model effectively diagnosed sepsis in primates (area under the curve,
      0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82).
      CONCLUSIONS: A model of sepsis based on reciprocal metabolomic and transcriptomic
      data was developed in primates and validated in two human patient cohorts. It is
      anticipated that the identified parameters will facilitate early diagnosis and
      management of sepsis.

PMID- 25054457
TI  - Three cost-utility analyses of screening for intracranial hemorrhage in neonates
      with hemophilia.
AB  - BACKGROUND: Intracranial hemorrhage (ICH) in the newborn period is a potential
      cause of serious morbidity and mortality in individuals with hemophilia. The
      incidence of ICH is estimated to be 2% to 4%; however, depending on the mode of
      delivery, it may be considerably higher. Considering the varying sensitivities
      and costs of various imaging modalities, there remains controversy surrounding
      universal cranial imaging. Cost-utility analysis is the ideal tool to display the
      consequences of a decision made. METHODS: We constructed a decision tree to
      evaluate the direct and indirect costs, possible outcomes, and probabilities of
      ICH in neonates with hemophilia. We created 3 decision analysis models to
      evaluate the cost-utility of different screening modalities for ICH: ultrasound,
      computed tomography, and magnetic resonance imaging. Within each model, 3
      different strategies were compared: screen all neonates; screen only neonates
      born by instrumented delivery; and not screen any neonates. A societal
      perspective was used for all models. The base case models were later reanalyzed
      in sensitivity analysis to account for uncertainties. RESULTS: Total costs for
      screening all neonates, screening only neonates born by instrumented delivery,
      and not screening any neonates were $9501, $9297, and $9347, respectively, for
      US, and $9761, $9351, and $9353, respectively, for CT. Screening instrumented
      deliveries using MRI had an incremental cost-effectiveness ratio of $12,440.
      CONCLUSIONS: Screening newborns born by an instrumented delivery appears to be
      the most cost-effective strategy irrespective of the imaging modality. Subsequent
      studies will require a longer time frame to factor in possible late effects of
      radiation, anesthesia, and the high cost of factor replacement and hospital
      admission.

PMID- 25054458
TI  - Effects of 6-week sling-based training of the external-rotator muscles on the
      shoulder profile in elite female high school handball players.
AB  - CONTEXT: In women's handball, the large numbers of throws and passes make the
      shoulder region vulnerable to overuse injuries. Repetitive throwing motions
      generate imbalance between shoulder internal- and external-rotator muscles. It
      has not yet been established whether sling-based training can improve shoulder
      external-rotator muscle strength. OBJECTIVE: This study investigated the
      effectiveness of a 6-wk strengthening program in improving shoulder functional
      profile in elite female high school handball players. DESIGN: Crossover study.
      SETTING: National elite handball training center. PARTICIPANTS: 25 elite female
      high school handball players. INTERVENTIONS: The program, completed twice per
      week for 6 wk, included sling-based strengthening exercises using a suspension
      trainer for external rotation with scapular retraction and scapular retraction
      alone. MAIN OUTCOMES: Maximal shoulder external- and internal-rotation strength,
      shoulder external- and internal-rotation range of motion (ROM), and maximal
      throwing velocity were assessed preintervention and postintervention for dominant
      and nondominant sides. RESULTS: After sling training, external- and internal
      rotation strength increased significantly for both sides (P <= .001, and P =
      .004, respectively), with the result that there was no significant change in
      external- and internal-rotation strength ratios for either the dominant or the
      nondominant shoulder. No significant differences were observed for external
      rotation ROM, while internal-rotation ROM decreased moderately, in particular in
      the dominant shoulder (P = .005). Maximal throwing velocity remained constant for
      the dominant arm, whereas a significant increase was found for the nondominant
      arm (P = .017). CONCLUSIONS: This 6-wk strengthening program was effective in
      improving shoulder external-rotator muscle strength but resulted in a decrease in
      the ROM in shoulder internal rotation, while throwing velocity remained stable.
      Adding a stretching program to this type of sling-based training program might
      help avoid potential detrimental effects on shoulder ROM.

PMID- 25054459
TI  - Is low and slow the way to go? Metronomic therapy in the treatment of pediatric
      brain tumors.

PMID- 25054462
TI  - Ependymoma: current treatment options and a look to the future.

PMID- 25054463
TI  - IFN-alpha for recurrent surgery- and radiation-refractory high-grade meningioma:
      a retrospective case series.
AB  - AIM: Limited literature is available regarding the treatment of recurrent surgery
      and radiation-refractory meningioma, and it primarily examines the treatment of
      low-grade (WHO grade 1) meningioma. Data regarding systemic therapy for recurrent
      high-grade meningioma are sparse. A retrospective case series of patients with
      recurrent WHO grade 2/3 meningioma treated with IFN-alpha following progression
      after surgery, radiotherapy and hydroxyurea was carried out, with the primary
      study objective of overall response rate, and median and 6-month progression-free
      survival (PFS). PATIENTS & METHODS: 35 patients (28 women and 17 men; median age
      63 years; range: 36-86 years) with recurrent high-grade meningioma (WHO grade 2
      [n = 22] or 3 [n = 13]) were treated with IFN-alpha (10 million units/m(2))
      subcutaneously every 2 days; one cycle was operationally defined as 4 weeks of
      IFN-alpha. Patients had progressed radiographically after prior therapy with
      surgery (35 out of 35), radiotherapy (35 out of 35; external-beam radiotherapy:
      35 out of 35; and stereotactic radiotherapy: 34 out of 35) and hydroxyurea
      chemotherapy (35 out of 35). One patient was also treated with a somatostatin
      analog before initiating IFN-alpha treatment. RESULTS: Patients received one to
      13 cycles (median: three) of IFN-alpha with moderate toxicity (100% of patients
      manifested grades 1-3 toxicity, of which only 20% were grade 3). There were no
      radiographic responses, 63% of patients had stable disease and 37% manifested
      progressive disease at first evaluation. PFS was 17% at 6 months (95% CI: 0.07
      0.31; median PFS: 12 weeks; 95% CI: 8-20 weeks; range: 4-52 weeks). Following
      progression on IFN-alpha, the majority of patients (60%) were subsequently
      treated on an alternative therapy. CONCLUSION: In this large retrospective
      series, IFN-alpha was moderately toxic, but appeared to have limited activity in
      patients with recurrent high-grade meningiomas.

PMID- 25054464
TI  - Retrospective analysis of the effects of steroid therapy and antidiabetic
      medication on survival in diabetic glioblastoma patients.
AB  - AIMS: Type 2 diabetes mellitus (DM2) affects 10% of the population, but little is
      known about how DM2 and antidiabetic medication impact glioblastoma (GBM)
      patients. PATIENTS & METHODS: We retrospectively reviewed GBM patients with DM2
      seen at a single institution from 1998 to 2010. RESULTS: Of 988 GBMs, 124 (12.6%)
      were affected by DM2. Thirty-four developed DM2 after steroid use and 89 had pre
      existing DM2. Median overall survival among diabetic GBMs was 10 months compared
      with 13 months among nondiabetics. Only 15% of diabetic patients achieved
      sustained steroid taper. Sixty-seven (54%) were managed with a single
      antidiabetic medication and, within this monotherapy group, Karnofsky Performance
      Score, resection status, steroid dependency and metformin use were the most
      important predictors of survival on multivariate analysis. CONCLUSION: The
      prevalence of DM2 among GBMs is similar to that of the general population. A more
      aggressive approach to steroid tapering and the choice of antidiabetic drug may
      improve survival within this patient population.

PMID- 25054465
TI  - Multidisciplinary management of pediatric intracranial ependymoma.
AB  - Pediatric intracranial ependymoma is a rare disease representing approximately 7%
      of brain tumors in children aged 15 years or younger. Due to the relative rarity
      of these tumors, a clear standard therapy has been difficult to establish. The
      mainstay of treatment is surgical resection and the majority of data demonstrate
      improved outcome with gross total resection. The standard of care also includes
      postoperative radiation therapy for most patients with grade II and III tumors.
      Chemotherapy has been used in many capacities in this disease; however, its
      optimal role is yet to be defined. Current controversies such as treatment with
      surgery alone in completely resected tumors, use of chemotherapy for subtotally
      resected tumors and use of adjuvant postradiation chemotherapy are incorporated
      into the design of the current Children's Oncology Group clinical trial.

PMID- 25054466
TI  - Stereotactic body radiotherapy: a new paradigm in the management of spinal
      metastases.
AB  - Spine stereotactic body radiotherapy is based on delivering high biologically
      effective doses to spinal metastases, with the intent to maximize both tumor and
      pain control. The purpose of this review is to outline the technical details of
      spine stereotactic body radiotherapy, contrast clinical outcomes to low
      biologically effective dose conventional palliative radiotherapy, discuss the
      role of surgery in the era of spine stereotactic body radiotherapy, and summarize
      the major serious adverse events that patients would otherwise not be at risk of
      with conventional radiotherapy.

PMID- 25054469
TI  - A study of phenylalanine side-chain dynamics in surface-adsorbed peptides using
      solid-state deuterium NMR and rotamer library statistics.
AB  - Extracellular matrix proteins adsorbed onto mineral surfaces exist in a unique
      environment where the structure and dynamics of the protein can be altered
      profoundly. To further elucidate how the mineral surface impacts molecular
      properties, we perform a comparative study of the dynamics of nonpolar side
      chains within the mineral-recognition domain of the biomineralization protein
      salivary statherin adsorbed onto its native hydroxyapatite (HAP) mineral surface
      versus the dynamics displayed by the native protein in the hydrated solid state.
      Specifically, the dynamics of phenylalanine side chains (viz., F7 and F14)
      located in the surface-adsorbed 15-amino acid HAP-recognition fragment (SN15:
      DpSpSEEKFLRRIGRFG) are studied using deuterium magic angle spinning ((2)H MAS)
      line shape and spin-lattice relaxation measurements. (2)H NMR MAS spectra and T1
      relaxation times obtained from the deuterated phenylalanine side chains in free
      and HAP-adsorbed SN15 are fitted to models where the side chains are assumed to
      exchange between rotameric states and where the exchange rates and a priori
      rotameric state populations are varied iteratively. In condensed proteins,
      phenylalanine side-chain dynamics are dominated by 180 degrees  flips of the
      phenyl ring, i.e., the "pi flip". However, for both F7 and F14, the number of
      exchanging side-chain rotameric states increases in the HAP-bound complex
      relative to the unbound solid sample, indicating that increased dynamic freedom
      accompanies introduction of the protein into the biofilm state. The observed
      rotameric exchange dynamics in the HAP-bound complex are on the order of 5-6 *
      10(6) s(-1), as determined from the deuterium MAS line shapes. The dynamics in
      the HAP-bound complex are also shown to have some solution-like behavioral
      characteristics, with some interesting deviations from rotameric library
      statistics. 

PMID- 25054467
TI  - Targeting core (mutated) pathways of high-grade gliomas: challenges of intrinsic
      resistance and drug efflux.
AB  - High-grade gliomas are the most common type of primary brain tumor and are among
      the most lethal types of human cancer. Most patients with a high-grade glioma
      have glioblastoma multiforme (GBM), the most malignant glioma subtype that is
      associated with a very aggressive disease course and short overall survival.
      Standard treatment of newly diagnosed GBM involves surgery followed by
      chemoradiation with temozolomide. However, despite this extensive treatment the
      mean overall survival is still only 14.6 months and more effective treatments are
      urgently needed. Although different types of GBMs are indistinguishable by
      histopathology, novel molecular pathological techniques allow discrimination
      between the four main GBM subtypes. Targeting the aberrations in the molecular
      pathways underlying these subtypes is a promising strategy to improve therapy. In
      this article, we will discuss the potential avenues and pitfalls of molecularly
      targeted therapies for the treatment of GBM.

PMID- 25054470
TI  - Effect of hydroxyethyl starch on postoperative kidney function in patients having
      noncardiac surgery.
AB  - BACKGROUND: Whether intraoperative use of hydroxyethyl starch impairs kidney
      function remains unknown. The authors thus tested the primary hypothesis that
      Hextend promotes renal injury in surgical patients. Secondarily, the authors
      evaluated the dose-outcome relationship, in-hospital and 90-day mortality, and
      whether the relationship between colloid use and acute kidney injury (AKI)
      depends on baseline risk for AKI. METHODS: The authors evaluated the data of
      44,176 adults without preexisting kidney failure who had inpatient noncardiac
      surgery from 2005 to 2012. Patients given a combination of colloid and
      crystalloid were propensity matched on morphometric, and baseline characteristics
      to patients given only crystalloid. The primary analysis was a proportional odds
      logistic regression with AKI as an ordinal outcome based on the Acute Kidney
      Injury Network classification. RESULTS: The authors matched 14,680 patients
      receiving colloids with 14,680 patients receiving noncolloids for a total of
      29,360 patients. After controlling for potential confounding variables, the odds
      of developing a more serious level of AKI with Hextend was 21% (6 to 38%) greater
      than with crystalloid only (P = 0.001). AKI risk increased as a function of
      colloid volume (P < 0.001). In contrast, the relationship between colloid use and
      AKI did not differ on baseline AKI risk (P = 0.84). There was no association
      between colloid use and risk of in-hospital (P = 0.81) or 90-day (P = 0.02)
      mortality. CONCLUSION: Dose-dependent renal toxicity associated with Hextend in
      patients having noncardiac surgery is consistent with randomized trials in
      critical care patients.

PMID- 25054471
TI  - Preparation of biofunctionalized quantum dots using microfluidic chips for
      bioimaging.
AB  - Biofunctionalized quantum dots (QDs), especially protein-coated QDs, are known to
      be useful targeted fluorescent labels for cellular and deep-tissue imaging. These
      nanoparticles can also serve as efficient energy donors in fluorescence resonance
      energy transfer (FRET) binding assays for the multiplexed sensing of tumor
      markers. However, current preparation processes for protein-functionalized QDs
      are laborious and require multiple synthesis steps (e.g. preparing them in high
      temperature, making them dispersible in water, and functionalizing them with
      surface ligands) to obtain a high quality and quantity of QD formulations,
      significantly impeding the progress of employing QDs for clinical diagnostics use
      such as a QD-based immunohistofluorescence assay. Herein, we demonstrate a one
      step synthesis approach for preparing protein-functionalized QDs using a
      microfluidic (MF) chip setup. Using bovine serum albumin (BSA) molecules as the
      surface ligand model, we first studied and optimized the MF reaction synthesis
      parameters (e.g. reaction temperature, and channel width and length) for making
      protein-functionalized QDs using COMSOL simulation modeling, followed by
      experimental verification. Moreover, in comparison with the BSA-functionalized
      QDs synthesized using the conventional bench-top method, BSA-QDs prepared using
      the MF approach exhibit a significantly higher protein-functionalization
      efficiency, photostability and colloidal stability. The proposed one-step MF
      synthesis approach provides a rapid, cost effective, and a small-scale production
      of nanocrystals platform for developing new QD formulations in applications
      ranging from cell labeling to biomolecular sensing. Most importantly, this
      approach will considerably reduce the amount of chemical waste generated during
      the trial-and-error stage of developing and perfecting the desired physical and
      optical properties of new QD materials. 

PMID- 25054472
TI  - Poly(N-cyanoethylethyleneimine): a new nanoscale template for biomimetic
      silicification.
AB  - Poly(N-cyanoethylethyleneimine) (PCEI) obtained by Michael addition of linear
      poly(ethyleneimine) (LPEI) with acrylonitrile provided novel nanocrystalline
      entities which could serve as catalytic templates affording nanosheet-based
      structured silica under mild conditions. 

PMID- 25054473
TI  - Biomedical Ph.D. students enrolled in two elite universities in the United
      kingdom and the United States report adopting multiple learning relationships.
AB  - OBJECTIVE: The ability to form multiple learning relationships is a key element
      of the doctoral learning environment in the biomedical sciences. Of these
      relationships, that between student and supervisor has long been viewed as key.
      There are, however, limited data to describe the student perspective on what
      makes this relationship valuable. In the present study, we discuss the findings
      of semi-structured interviews with biomedical Ph.D. students from the United
      Kingdom and the United States to: i) determine if the learning relationships
      identified in an Australian biomedical Ph.D. cohort are also important in a
      larger international student cohort; and ii) improve our understanding of student
      perceptions of value in their supervisory relationships. STUDY DESIGN: 32
      students from two research intensive universities, one in the United Kingdom (n =
      17), and one in the United States (n = 15) were recruited to participate in a
      semi-structured interview. Verbatim transcripts were transcribed, validated and
      analysed using a Miles and Huberman method for thematic analysis. RESULTS:
      Students reported that relationships with other Ph.D. students, post-doctoral
      scientists and supervisors were all essential to their learning. Effective
      supervisory relationships were perceived as the primary source of high-level
      project guidance, intellectual support and confidence. Relationships with fellow
      students were viewed as essential for the provision of empathetic emotional
      support. Technical learning was facilitated, almost exclusively, by relationships
      with postdoctoral staff. CONCLUSIONS: These data make two important contributions
      to the scholarship of doctoral education in the biomedical sciences. Firstly,
      they provide further evidence for the importance of multiple learning
      relationships in the biomedical doctorate. Secondly, they clarify the form of a
      'valued' supervisory relationship from a student perspective. We conclude that
      biomedical doctoral programs should be designed to contain a minimum level of
      formalised structure to promote the development of multiple learning
      relationships that are perceived as key to student learning.

PMID- 25054474
TI  - Postgraduate nursing student knowledge, attitudes, skills, and confidence in
      appropriately referencing academic work.
AB  - Preventing plagiarism is an ongoing issue for higher education institutions.
      Although plagiarism has been traditionally seen as cheating, it is increasingly
      thought to be the result of poor referencing, with students reporting
      difficulties citing and referencing bibliographic sources. This study examined
      the academic knowledge, attitude, skills, and confidence of students in a school
      of nursing to understand poor referencing. A cross-sectional quantitative and
      qualitative survey was distributed to postgraduate (N = 1,000) certificate,
      diploma, and master's students. Quantitative data gathered demographics, cultural
      and linguistic background, and use of technology. Thematic analysis discovered
      patterns and themes. Results showed participants understood requirements for
      referencing; half indicated poor referencing was due to difficulty referencing
      Internet sources or losing track of sources, and many lacked confidence in key
      referencing tasks. Despite this, 50% did not make use of referencing resources.
      Overall, these data suggest incorrect referencing is rarely intentional and
      predominantly caused by skills deficit.

PMID- 25054475
TI  - Influence of international service-learning on nursing student self-efficacy
      toward cultural competence.
AB  - One method of gaining knowledge, skills, and experience with different cultures
      for nurses and nursing students is through an international immersion program of
      training in language, culture, and community nursing. This article presents a
      qualitative and quantitative research study of the influence of a 2-week service
      learning medical experience of a nursing student group who traveled abroad to
      Belize, Central America.

PMID- 25054476
TI  - Improving communication in distance-accessible advanced practice nursing courses
      via instructor presence.
AB  - By using principles of instructor presence, faculty of distance-accessible
      nursing courses can foster a climate of learning that supports student
      achievement and provides role modeling for communication. Faculty used principles
      of instructional design, facilitation of student discourse, and clear direct
      instruction to improve the learning experiences of approximately 300 graduate
      nursing students taking part in a health assessment course. Specific suggestions
      for faculty that take place before and throughout the semester are offered.

PMID- 25054477
TI  - Reattendance and chlamydia retesting rates at 12 months among young people
      attending Australian general practice clinics 2007-10: a longitudinal study.
AB  - Background Clinical guidelines commonly recommend annual chlamydia (Chlamydia
      trachomatis) testing in young people. General practice (GP) clinics can play an
      important role in annual testing, as a high proportion of young people attend
      these clinics annually; however, little is known about the timing of attendance
      and testing in this setting. METHODS: The Australian Collaboration for
      Coordinated Enhanced Sentinel Surveillance of Sexually Transmitted Infections and
      Blood-Borne Viruses system extracted consultation and pathology data on 16-29
      year-olds attending 25 GP clinics in 2007-10. We calculated the proportion of
      individuals with an initial negative test that reattended at 12 months (+/-3
      months) and retested at 12 months (+/-3 months). Individuals with an initial
      positive test were excluded, as guidelines recommend retesting at 3 months.
      RESULTS: Among 3852 individuals who had an initial negative test, 2201 (57.1%)
      reattended at ~12 months; reattendance was higher among females (60.8%) than
      males (44.1%; P<0.001) and higher among 16-19-year-olds (64.2%) than 25-29-year
      olds (50.8%; P<0.001). Of 2201 individuals who reattended at 12 months, 377 had a
      chlamydia test (retesting rate of 9.8%); retesting was higher among females
      (10.8%) than males (6.1%; P<0.01) and higher among 16-19-year-olds (13.3%) than
      25-29-year-olds (7.5%; P<0.001). CONCLUSION: Although over half of young people
      reattended their GP clinic ~1 year after a negative chlamydia baseline test, only
      9.8% were retested at this visit. Strategies are needed to promote regular
      attendance and testing to both patients and clinicians.

PMID- 25054478
TI  - A stress responsive gene of Fortunella crassifolia FcSISP functions in salt
      stress resistance.
AB  - Exploration of genes functioning in salt tolerance is crucial for generating
      transgenic plants with enhanced salt tolerance. In this study, we report the
      isolation and functional characterization of a stress-responsive gene FcSISP from
      Meiwa kumquat (Fortunella crassifolia). FcSISP encodes a putative protein of 47
      amino acids, with a calculated molecular mass of 4.94 kDa and theoretical
      isoelectric point of 3.76, and was localized in the nucleus. Transcript levels of
      FcSISP were induced by dehydration, cold, salt and bacterium causing citrus
      canker, and hormones (salicylic acid and abscisic acid), with the greatest
      induction under salt treatment. Overexpression of FcSISP in tobacco (Nicotiana
      nudicaulis) conferred enhanced salt tolerance. The transgenic lines accumulated
      lower Na(+) contents, leading to reduced Na/K ratio, but accumulated more proline
      than the wild type (WT). Steady state mRNA levels of genes involved in Na(+)
      exchange (three SOS genes and three NHX genes) and proline synthesis (P5CS and
      P5CR) were higher in the transgenic lines in comparison with WT. Moreover,
      overexpression of FcSISP in trifoliate orange [Poncirus trifoliata (L.) Raf.], a
      widely-used and salt-sensitive citrus rootstock, led to elevated salt tolerance.
      Taken together, the data demonstrate that FcSISP plays a positive role in salt
      tolerance and that it holds a great potential for engineering salt tolerance in
      crops. 

PMID- 25054479
TI  - Focus on pMDI and VHC; past, present, future!

PMID- 25054480
TI  - In vitro characterization of the OptiChamber Diamond valved holding chamber.
AB  - BACKGROUND: Use of a valved holding chamber (VHC) in conjunction with a
      pressurized metered dose inhaler (pMDI) can reduce issues relating to poor
      actuation-inhalation coordination and potentially improve the lung deposition of
      aerosol, compared with use of a pMDI alone. However, the performance of a VHC is
      influenced by different device-related factors, including the size and shape of
      the VHC and the material it is manufactured from (conventional versus
      antistatic). This study aimed to provide an in vitro characterization of an
      antistatic VHC, the OptiChamber Diamond VHC, comparing the aerodynamic particle
      size distribution of aerosol delivered via this VHC with results from a second
      antistatic VHC and a conventional VHC. METHODS: The pMDI drug formulations
      (albuterol, suspension; beclomethasone dipropionate, solution) were connected to
      a Next Generation Impactor, either directly (pMDI alone tests) or via a VHC (VHC
      tests). The pMDIs were actuated (*10 per product pair) and tested at extraction
      flow rates of 15 L/min and 30 L/min, without any time delay between actuation and
      inhalation. Dose delivery using the two pMDI drug formulations was compared, and
      is presented with reference to key aerodynamic particle size parameters. RESULTS:
      Compared with tests on pMDIs alone, use of a VHC increased the dose of aerosol
      within the respirable range, particularly at a 15 L/min flow rate. Between-VHC
      comparisons indicated that the two antistatic VHCs were equivalent. Delivery of
      albuterol appeared to be influenced by the VHC used, but beclomethasone
      dipropionate seemed unaffected. CONCLUSIONS: The two antistatic VHCs were
      equivalent for both pMDI brands. Aerosol delivered from the antistatic VHCs at 15
      L/min had a higher proportion of fine particles compared with the conventional
      VHC.

PMID- 25054481
TI  - The evolution of spacers and valved holding chambers.
AB  - Spacers and valved holding chambers (VHCs) are pressurized metered dose inhaler
      (pMDI) accessory devices, designed to overcome problems that patients commonly
      experience when administering aerosol via a pMDI. Spacers were developed in
      direct response to patient-related issues with pMDI technique, particularly, poor
      coordination between actuation and inhalation, and local side-effects arising
      from oropharyngeal deposition. Current clinical guidelines indicate the need for
      widespread prescription and use of spacers, but, despite their apparent ubiquity,
      the devices themselves are, unfortunately, all too commonly "disused" by
      patients. An understanding of the background from which spacers developed, and
      the key factors influencing the optimization of the spacer and the later VHC, is
      crucial to developing an appreciation of the potential of these devices, both
      contemporary and future, for improving the delivery of pressurized aerosols to
      patients. This review, informed by a full patent search and an extensive
      scientific literature review, takes into account the clinical and laboratory
      evidence, commercial developments, and the sometimes serendipitous details of
      scientific anecdotes to form a comprehensive perspective on the evolution of
      spacers, from their origins, in the early days of the pMDI, up to the present
      day.

PMID- 25054482
TI  - An instrumented valved holding chamber with facemask to measure application
      forces and flow in young asthmatic children.
AB  - BACKGROUND: Pressurized metered dose inhalers (pMDIs), combined with a valved
      holding chamber (VHC) and facemask, are often used for young asthmatic children.
      When using a VHC with facemask, a tight seal between the facemask and the
      patient's face is crucial for efficient pulmonary aerosol delivery. Realistic
      parameters for in vitro bench testing are not well known. A custom instrumented
      OptiChamber Diamond VHC, known as the Facemask Datalogger, was developed to
      measure the real-time application of force and the air flow through the VHC and
      facemask. METHODS: Thirty asthmatic children aged 1-4 years from the Kinderhaven
      outpatient clinic, who were prescribed a pMDI/VHC with facemask for regular use,
      were included in the study. Using the Facemask Datalogger, the parent applied the
      facemask to the face of the child during normal tidal breathing, and force and
      flow were recorded. This was repeated three times. A video of the procedure was
      made and scored on cooperation (scale of 1-5). RESULTS: Mean application force
      was 4 N (+/- 1.5) equal to 411 g (+/- 156) when expressed as a weight equivalent;
      intrasubject variability in application force was 23% (+/- 23); intersubject
      variability in application force was 39%; time needed to empty the VHC was 4.5
      sec (+/- 2.9); breaths needed to empty the VHC were 2.9 (+/- 1.1); and mean
      cooperation score was 4.3 (+/- 0.8). Age was correlated with time (r=-0.49;
      p=0.006) and breaths needed to empty the VHC (r=-0.75; p<0.001), and observer
      cooperation score (r=0.65; p<0.001). CONCLUSIONS: The Facemask Datalogger is
      useful for measuring application force and air flow in vivo. Mean application
      force was lower than assumed in other studies. Older children emptied the VHC
      faster, with fewer breaths and better cooperation. The data from this study can
      be used in the future development and testing of new facemasks and VHCs.

PMID- 25054483
TI  - Lung deposition of 99mTc-radiolabeled albuterol delivered through a pressurized
      metered dose inhaler and spacer with facemask or mouthpiece in children with
      asthma.
AB  - BACKGROUND: Research on the use of a pressurized metered dose inhaler (pMDI) with
      spacer (pMDI/spacer) in children has indicated oral inhalation via the spacer
      mouthpiece is more efficient than the combination of oral and nasal inhalation
      that occurs when a pMDI/spacer is used with a facemask. Changes in pMDI
      formulations and developments in spacer and facemask designs have highlighted the
      need for new comparative studies of spacer use, particularly focusing on the age
      at which children can be taught to transition from use of a pMDI/spacer with
      facemask to use of the spacer mouthpiece. METHODS: Twelve children aged 3-5 years
      (7 males) with stable asthma were recruited. Of these, 10 children (6 males)
      completed both arms of the study. A transmission scan of each compliant subject
      was taken using a 37 MBq (99m)Tc flood source. Actuations (2-3) of a (99m)Tc
      radiolabeled albuterol pMDI were administered through an antistatic spacer
      (OptiChamber Diamond) via either a facemask (medium LiteTouch facemask), or the
      spacer mouthpiece. The subject's inhalation pattern was simultaneously recorded
      using a pMDI Datalogger, and narrative data relating to tolerance and compliance
      were documented. Anterior and posterior planar scintigraphic scans were taken
      immediately after aerosol administration. RESULTS: Mean (SD) lung deposition (%
      total dose) was 18.1 (9.1)% with the facemask and 22.5 (7.9)% with the spacer
      mouthpiece (p>0.05). Peripheral lung deposition (expressed as peripheral:central
      (P:C) ratio) was higher in 7 out of 10 children with the facemask compared with
      the spacer mouthpiece: 1.3 (0.26) vs. 1.2 (0.35); (p=0.11). Head and neck
      deposition was higher with use of the facemask compared with the spacer
      mouthpiece: 19.7 (10.6)% vs. 10.8 (5.3)% (p=0.011). CONCLUSIONS: Lung deposition
      achieved using the spacer with facemask was higher than previously reported, with
      a difference of only 4.4% of total dose measured compared to the deposition with
      mouthpiece. This may be due to a combination of factors including pMDI
      formulation, and use of an antistatic spacer with a flexible, well-fitting
      facemask.

PMID- 25054484
TI  - Low-temperature sputtered nickel oxide compact thin film as effective electron
      blocking layer for mesoscopic NiO/CH3NH3PbI3 perovskite heterojunction solar
      cells.
AB  - We introduce the use of low temperature sputtered NiOx thin film, which
      substitutes the PEDOT-PSS and solution-processed NiOx as an effective electron
      blocking layer for mesoscopic NiO/CH3NH3PbI3 perovskite solar cells. The
      influences of film thickness and oxygen doping on the photovoltaic performances
      are scrutinized. The cell efficiency has been improved from 9.51 to 10.7% for
      devices using NiOx fabricated under pure argon atmosphere. With adequate doping
      under 10% oxygen flow ratio, we achieved power conversion efficiency of 11.6%.
      The procedure is large area scalable and has the advantage for cost-effective
      perovskite-based photovoltaics. 

PMID- 25054485
TI  - Multicolor imaging of cancer cells with fluorophore-tagged aptamers for single
      cell typing.
AB  - The discrimination of the type of cancer cells remains challenging due to the
      subtle differences in their expression of membrane receptors. In this work, we
      developed a multicolor cell imaging method for distinguishing the type of cancer
      cells with fluorophore-tagged aptamers. We found that the interaction between
      aptamers and cancer cells was affected by both of the sequence of aptamers and
      the labeled dyes. As the co-ownership of biomarkers for different cancer cell
      lines, the fluorophore-tagged aptamers interacted with different cancer cell
      lines in different degree, resulting in a distinct color to discriminate the type
      of cancer cells at single cell level. Taking advantage of the cross-reactive
      ability of the fluorophore-tagged aptamers, we could not only distinguish the
      cancerous cells quickly from large quantities of noncancerous cells, but also
      identify the type of the cancerous cells. This work has potential application for
      cancer diagnostic and therapy in the future. 

PMID- 25054486
TI  - Long-term results of a postoperative pneumonia prevention program for the
      inpatient surgical ward.
AB  - IMPORTANCE: Pneumonia is the third most common complication in postoperative
      patients and is associated with significant morbidity and high cost of care.
      Prevention has focused primarily on mechanically ventilated patients. This study
      outlines the results of the longest-running postoperative pneumonia prevention
      program for nonmechanically ventilated patients, to our knowledge. OBJECTIVE: To
      present long-term results (2008-2012) of a standardized postoperative ward
      acquired pneumonia prevention program introduced in 2007 on the surgical ward of
      our hospital and compare our postintervention pneumonia rates with those captured
      in the American College of Surgeons National Surgical Quality Improvement Program
      (ACS-NSQIP). We also estimate the cost savings attributable to the pneumonia
      prevention program. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study
      at a university-affiliated Veterans Affairs hospital of all noncardiac surgical
      patients with ward-acquired postoperative pneumonia. INTERVENTION: A previously
      described standardized postoperative pneumonia prevention program for patients on
      the surgical ward. MAIN OUTCOME AND MEASURE: Ward-acquired postoperative
      pneumonia. RESULTS: Between 2008 and 2012, there were 18 cases of postoperative
      pneumonia among 4099 at-risk patients hospitalized on the surgical ward, yielding
      a case rate of 0.44%. This represents a 43.6% decrease from our preintervention
      rate (0.78%) (P = .01). The pneumonia rates in all years were lower than the
      preintervention rate (0.25%, 0.50%, 0.58%, 0.68%, and 0.13% in 2008-2012,
      respectively). The overall pneumonia rate in ACS-NSQIP was 2.56% (14,033 cases of
      pneumonia among 547,571 at-risk patients), which is 582% higher than the
      postintervention rate at our ward. Using a national average of $46,400 in
      attributable health care cost of postoperative pneumonia and a benchmark of a
      43.6% decrease in pneumonia rate achieved at our facility over the 5-year study
      period, a similar percentage of decrease in pneumonia occurrence at ACS-NSQIP
      hospitals would represent approximately 6118 prevented pneumonia cases and a cost
      savings of more than $280 million. CONCLUSIONS AND RELEVANCE: The standardized
      pneumonia prevention program achieved substantial and sustained reduction in
      postoperative pneumonia incidence on our surgical ward; its wider adoption could
      improve postoperative outcomes and reduce overall health care costs.

PMID- 25054487
TI  - Rhipicephalus (Boophilus) microplus resistant to acaricides and ivermectin in
      cattle farms of Mexico.
AB  - Ticks and the diseases they transmit cause great economic losses to livestock in
      tropical countries. Non-chemical control alternatives include the use of
      resistant cattle breeds, biological control and vaccines. However, the most
      widely used method is the application of different chemical classes of acaricides
      and macrocyclic lactones. Populations of the cattle tick, Rhipicephalus
      (Boophilus) microplus, resistant to organophosphates (OP), synthetic pyrethroids
      (SP), amitraz and fipronil have been reported in Mexico. Macrocyclic lactones are
      the most sold antiparasitic drug in the Mexican veterinary market. Ivermectin
      resistant populations of R. (B.) microplus have been reported in Brazil, Uruguay
      and especially in Mexico (Veracruz and Yucatan). Although ivermectin resistance
      levels in R. (B.) microplus from Mexico were generally low in most cases, some
      field populations of R. (B.) microplus exhibited high levels of ivermectin
      resistance. The CHPAT population showed a resistance ratio of 10.23 and 79.6 at
      lethal concentration of 50% and 99%, respectively. Many field populations of R.
      (B.) microplus are resistant to multiple classes of antiparasitic drugs,
      including organophosphates (chlorpyrifos, coumaphos and diazinon), pyrethroids
      (flumethrin, deltamethrin and cypermethrin), amitraz and ivermectin. This paper
      reports the current status of the resistance of R. (B.) microplus to acaricides,
      especially ivermectin, in Mexican cattle. 

PMID- 25054488
TI  - Parasitological and immunological diagnoses from feces of captive-bred snakes at
      Vital Brazil Institute.
AB  - Fecal samples from 56 snakes at the Vital Brazil Institute, in the city of
      Niteroi, Rio de Janeiro, were tested using the sedimentation and flotation
      techniques to investigate the evolutionary forms of parasites such as helminths
      and protozoa, and using enzyme immunoassay techniques to detect antigens of
      Cryptosporidium sp. and Giardia sp. Among the animals tested, 80.3% were positive
      for parasites. Out of these, there were 16 Bothrops jararaca, 16 B. jararacussu
      and 13 Crotalus durissus. The prevalence of parasitic nematodes was 41.1%, and
      nematodes were found in all three snake species. Among these, the most frequent
      finding was eggs of Kalicephalus sp., which were diagnosed in 25% of the snakes.
      The positivity for protozoa detected using parasite concentration techniques was
      75%, including oocysts of Caryospora sp. in 75%, cysts with morphology similar to
      Giardia sp. 3.6%, amoeboid cysts in 41.1% and unsporulated coccidia oocysts in
      8.9%. Immunoassays for Cryptosporidium sp. antigens produced positive findings in
      60.7%. Pseudoparasites were detected in 64.3%. These results show that there is a
      need to improve the sanitary handling of captive-bred snakes, and also for the
      animal house that supplies rodents to feed them. The results also highlight that
      diagnostic tests should be performed periodically on stool specimens from captive
      bred snakes. 

PMID- 25054489
TI  - Risk factors for anthelmintic resistance development in cattle gastrointestinal
      nematodes in Argentina.
AB  - Risk factors for anthelmintic resistance (AR) on bovine ranches were studied.
      Data were derived from a survey made to 50 ranch owners, who had conducted a
      faecal egg-count-reduction test. The questionnaire contained descriptors of
      bovine ranch management and nematode control. A case-control design study was
      undertaken and AR cases were present in 26 herds. Associations between the binary
      outcome variable (AR versus not AR) and risk factors recorded in the
      questionnaire were evaluated. Variables associated with the presence of AR at P<
      0.15 and/or odds ratio (OR) > 2 were subjected to a multivariable logistic
      regression model. The main effects contributing to general AR (avermectin AVM
      and/or benzimidazole) in the final model were total number of annual treatments
      (OR 7.68; 95% CI 2.4 to 28.3) and use of more than 75% of AVM in the past (OR=
      18.6; 95% CI 1.3 to 97.3), whereas for AVM resistance alone were total number of
      AVM annual treatments (OR= 11.5; 95% CI 2.9 to 45.5) and number of AVM Nov-Jan
      treatments (OR= 5.8; 95% CI 1.71 to 47.9). The results showed that treatment
      frequency, date of treatment and frequency of treatment in the past with a single
      drug were the main risk factors involved in AR development. 

PMID- 25054490
TI  - Lectin, hemolysin and protease inhibitors in seed fractions with ovicidal
      activity against Haemonchus contortus.
AB  - Bioactive molecules of plant species are promising alternatives for the chemical
      control of gastrointestinal nematodes in ruminants. Extracts of native and exotic
      seed species from Brazil's semi-arid region were tested in vitro in an egg hatch
      assay and the bioactivity of their proteins was investigated. Each seed species
      was subjected to three extractions with three types of solvents. All the seeds
      showed ovicidal activity, which varied according to the solvents. Higher ovicidal
      activity was found in the molecule fractions of low molecular weight (<12 kDa)
      for Albizia lebbeck, Ipomoea asarifolia, Jatropha curcas, Libidibia ferrea,
      Moringa oleifera and Ricinus communis (P<0.05, Bonferroni test). The two
      fractions of Crotalaria spectabilis showed the same ovicidal activity (P>0.05,
      Bonferroni test). Hemagglutinating activity was detected in the fractions of C.
      spectabilis and M. oleifera fractions, hemolysin activity in the A. lebbeck and
      M. oleifera fractions, serine protease inhibitory activity in the A. lebbeck, I.
      asarifolia, J. curcas, M. oleifera and R. communis fractions, cysteine protease
      inhibitor activity in the M. oleifera fraction, and no protein activity in the L.
      ferrea fraction. The results of this work reveal new plant species with a
      potential for use in controlling nematode parasites in goats, thus opening a new
      field of research involving plant protein molecules with ovicidal properties. 

PMID- 25054491
TI  - Parasitism by Sphincterodiplostomum musculosum (Digenea, Diplostomidae)
      metacercariae in the eyes of Steindachnerina insculpta (Characiformes,
      Curimatidae).
AB  - New occurrences and effects of parasitism by metacercariae in fish eyes have
      recently been discussed in many studies. The aim of the present study was to
      evaluate the infection levels of the eye flukes Sphincterodiplostomum musculosum
      Dubois, 1936 (metacercariae) in Steindachnerina insculpta (Fernadez-Yepez, 1948)
      from three ecosystems under the influence of the Jurumirim reservoir
      (Paranapanema, Taquari and Veados Rivers). A total of 174 fish specimens were
      sampled between April 2011 and April 2012. There were high levels of infection by
      S. musculosum metacercariae in the eyes of S. insculpta from all the sampled
      ecosystems, thus presenting broad geographical distribution. The histological
      analyses revealed that the metacercariae were apparently lodged behind the
      retina. The smaller fish from the Taquari River were less parasitized by
      metacercariae than the adults. This pattern can be explained by the cumulative
      effect of parasitism, as demonstrated by the positive correlation between the
      abundance of metacercariae and fish body size. 

PMID- 25054492
TI  - Reassessment of the potential economic impact of cattle parasites in Brazil.
AB  - The profitability of livestock activities can be diminished significantly by the
      effects of parasites. Economic losses caused by cattle parasites in Brazil were
      estimated on an annual basis, considering the total number of animals at risk and
      the potential detrimental effects of parasitism on cattle productivity. Estimates
      in U.S. dollars (USD) were based on reported yield losses among untreated animals
      and reflected some of the effects of parasitic diseases. Relevant parasites that
      affect cattle productivity in Brazil, and their economic impact in USD billions
      include: gastrointestinal nematodes - $7.11; cattle tick (Rhipicephalus
      (Boophilus) microplus) - $3.24; horn fly (Haematobia irritans) - $2.56; cattle
      grub (Dermatobia hominis) - $0.38; New World screwworm fly (Cochliomyia
      hominivorax) - $0.34; and stable fly (Stomoxys calcitrans) - $0.34. The combined
      annual economic loss due to internal and external parasites of cattle in Brazil
      considered here was estimated to be at least USD 13.96 billion. These findings
      are discussed in the context of methodologies and research that are required in
      order to improve the accuracy of these economic impact assessments. This
      information needs to be taken into consideration when developing sustainable
      policies for mitigating the impact of parasitism on the profitability of
      Brazilian cattle producers. 

PMID- 25054493
TI  - Haematological and parasitological assessment of silver catfish Rhamdia quelen
      farmed in Southern Brazil.
AB  - This study evaluated for two years the haematological parameters and the
      occurrence of gill parasites in silver catfish Rhamdia quelen, farmed in the
      state of Santa Catarina, southern Brazil. Between March 2010 and January 2012, a
      total of 137 fish were caught in a fish farm to compare the haematological and
      parasitological analysis, during hot and cold seasons. Simultaneously, water
      quality parameters were measured in the pond to analyze the relationship between
      environmental conditions and haematology and parasitism. During the hot season,
      there was an increase in water temperature, electrical conductivity and ammonia
      followed by a decrease in dissolved oxygen, pH, transparency and alkalinity. Two
      species of Monogenea were observed in the gills, Aphanoblastella mastigatus
      (Dactylogyridae) and Scleroductus sp. (Gyrodactylidae). Additionally, during this
      season, there was a significant increase (p<0.05) in the mean intensity of
      infection by Monogenea, as well as total leukocytes number, thrombocytes and
      lymphocytes, and a reduction in monocytes. The changes might be caused by
      parasitism and/or environmental variations between seasons. 

PMID- 25054494
TI  - Streblidae (Diptera) on bats (Chiroptera) in an area of Atlantic Forest, state of
      Rio de Janeiro.
AB  - Because of the few records of Streblidae on bats, despite extensive study on
      these mammals in the state of Rio de Janeiro, a survey was carried out in an area
      of Atlantic Forest, in the municipality of Nova Iguacu, known as the Tingua
      region. Thirteen species were added to the list of Streblidae in the state of Rio
      de Janeiro, of which two were new records for Brazil. Thirty-one species have now
      been reported this state. 

PMID- 25054495
TI  - Ectoparasites of Nile tilapia (Oreochromis niloticus) in cage farming in a
      hydroelectric reservoir in Brazil.
AB  - For this study, we performed a parasitological analysis of cage-cultured Nile
      tilapia (Oreochromis niloticus) from the Agua Vermelha Reservoir, Southeastern
      Brazil, and verified relationships with limnological data, seasonality, and fish
      growth phase. From March 2010 to March 2011, sixty-three specimens of O.
      niloticus in three growth phases (i.e., initial, intermediate, and final) were
      collected. All fish specimens were infested with at least one ectoparasite
      species (prevalence = 100%). Five species of protozoans (Trichodina compacta,
      Trichodina magna, Ichthyophthirius multifiliis, Piscinoodinium pillulare, and
      Epistylis sp.) and five species of monogenoids (Cichlidogyrus halli,
      Cichlidogyrus thurstonae, Cichlidogyrus sp. 1, Scutogyrus longicornis, and
      Gyrodactylus sp.) were observed. The abundance of Trichodina spp. and the
      prevalence of Epistylis sp. were higher in the dry season, and the prevalence of
      C. halli was higher in the rainy season. For the majority of ectoparasites found
      in this study, fish in the intermediate and final phases had higher parasitism
      rates than those in the initial phase. The data presented may help fish farmers
      to understand the parasite dynamics of the fish species studied in cage-farming
      systems. 

PMID- 25054496
TI  - Comparative evaluation of several methods for Canine Visceral Leishmaniasis
      diagnosis.
AB  - The aim of the present study was to evaluate the serological methods using ELISA
      with recombinant-rK39 (ELISA-rK-39) and soluble extract-SE (ELISA-SE) antigens,
      the indirect fluorescence antibody test (IFAT) in comparison to an
      immunochromatography rapid diagnostic test (RDT-rK39) and with a direct
      parasitological exam (PA) for Canine Visceral Leishmaniasis (CVL) diagnosis. The
      results showed that 89% (60/67) of the dogs were positive for at least one
      serological diagnostic test. ELISA-SE was the test that detected anti-Leishmania
      antibodies in the serum of the highest number of dogs (71.6%) followed by ELISA
      rK39 (65.7%), IFAT (65.7%) and RDT-rK39 (55.2%). PA detected the lowest numbers
      (40.3%) of positive dogs. In relation to the total of examined dogs, the Kappa
      indexes (p <= 0.05) showed a good agreement between ELISA-SE and IFAT (88.1%; k =
      0.7237), and it was also observed in the comparison of RDT-rK39 with ELISA-SE
      (83.6%, k= 0.6561), IFAT (83.5%, k= 0.6605) and PA (85.0%, k= 0.7074). A bad
      agreement was detected in any association of ELISA-rk39 with the other tests in
      either symptomatic or asymptomatic animals. ELISA as well as RDT using
      recombinant antigenic protein (rK39) were the methods that detected the lowest
      prevalence rates (33.3%) of CVL in asymptomatic dogs. In conclusion, only one
      test does not adequately identify dogs with CVL and it is necessary the
      association of two or more diagnostic tests. Because of the good agreement
      indexes of RDT-rK39 when evaluated with ELISA-SE, IFAT and PA it was suggested as
      a complementary method to be used in association with either ELISA-SE or IFAT,
      particularly in the symptomatic dogs. Furthermore, new studies are recommended in
      order to improve the sensitivity of tests mainly for asymptomatic dogs. 

PMID- 25054497
TI  - Assessment and partial purification of serine protease inhibitors from
      Rhipicephalus (Boophilus) annulatus larvae.
AB  - Ticks are rich sources of serine protease inhibitors, particularly those that
      prevent blood clotting and inflammatory responses during blood feeding. The tick
      Rhipicephalus (Boophlus) annulatus is an important ectoparasite of cattle. The
      aims of this study were to characterize and purify the serine protease inhibitors
      present in R. (B.) annulatus larval extract. The inhibitors were characterized by
      means of one and two-dimensional reverse zymography, and purified using affinity
      chromatography on a trypsin-Sepharose column. The analysis on one and two
      dimensional reverse zymography of the larval extract showed trypsin inhibitory
      activity at between 13 and 40 kDa. Through non-reducing SDS-PAGE and reverse
      zymography for proteins purified by trypsin-Sepharose affinity chromatography,
      some protein bands with molecular weights between 13 and 34 kDa were detected.
      Western blotting showed that five protein bands at 48, 70, 110, 130 and 250 kDa
      reacted positively with immune serum, whereas there was no positive reaction in
      the range of 13-40 kDa. Serine protease inhibitors from R. (B.) annulatus have
      anti-trypsin activity similar to inhibitors belonging to several other hard tick
      species, thus suggesting that these proteins may be useful as targets in anti
      tick vaccines. 

PMID- 25054498
TI  - Antifungal activity of Stenotrophomonas maltophilia in Stomoxys calcitrans
      larvae.
AB  - The microbiota present in Stomoxys calcitrans larvae may assist their survival in
      contaminated environments through production of inhibitory substances.
      Bacteriological identification methods, the polymerase chain reaction (PCR) and
      scanning electron microscopy (SEM) were used to detect a bacterium naturally
      present in mucus and macerated S. calcitrans larvae. The antifungal activity was
      determined based on the results from disk diffusion tests on an artificial solid
      medium. The bacterium was identified as Stenotrophomonas maltophilia and
      presented antifungal activity against Beauveria bassiana sensu lato isolates CG
      138, CG 228 and ESALQ 986. This result suggests that the larval microbiota is a
      factor that can compromise the use of B. bassiana s.l. fungus for biological
      control of S. calcitrans larvae. 

PMID- 25054499
TI  - Occurrence of immature forms of culicids (Insecta: Diptera) in the northeastern
      region of Brazil.
AB  - The Culicidae family is represented by approximately 3,610 species, among which
      many are involved in transmission of pathogens and parasites, thus presenting
      great medical-veterinary importance. In Brazil, the state of Pernambuco is
      considered an endemic area for many diseases vectored by mosquitoes, such as
      human and canine filariasis, caused by Wuchereria bancrofti and Dirofilaria
      immitis, respectively. The aim of this study was to evaluate the occurrence of
      immature forms of culicids, over an one-year period, in a specific area of
      northeastern region of Brazil. Culicids larvae were collected from traps located
      on the ground and in treetops, between october 2012 and september 2013. Ten
      different species of culicids were identified. The greatest number of larvae were
      collected in september 2013 and the lowest number in december 2012. Stegomyia
      (Stegomyia) albopicta (46.45%; 5,908/12,718), Culex (Culex) maxi (35.56%;
      4,523/12,718) and Limatus durhamii (12.58%; 1,600/12,718) were the most frequent
      species. The human and animal populations living in the study area are exposed to
      culicids and transmission agents throughout the year, especially after the rains.
      Therefore, control and prevention measures against culicids must be adopted in
      the study area. 

PMID- 25054500
TI  - Post-mortem hemoparasite detection in free-living Brazilian brown brocket deer
      (Mazama gouazoubira, Fischer 1814).
AB  - Tick-borne infections can result in serious health problems for wild ruminants,
      and some of these infectious agents can be considered zoonosis. The aim of the
      present study was the post-mortem detection of hemoparasites in free-living
      Mazama gouazoubira from Minas Gerais state, Brazil. The deer samples consisted of
      free-living M. gouazoubira (n = 9) individuals that died after capture. Necropsy
      examinations of the carcasses were performed to search for macroscopic
      alterations. Organ samples were collected for subsequent imprint slides, and
      nested PCR assays were performed to detect hemoparasite species. Imprint slide
      assays from four deer showed erythrocytes infected with Piroplasmida small
      trophozoites, and A. marginale corpuscles were observed in erythrocytes from two
      animals. A. marginale and trophozoite co-infections occurred in two deer. A
      nested PCR analysis of the organs showed that six of the nine samples were
      positive for Theileria sp., five were positive for A. phagocytophilum and three
      were positive for A. marginale, with co-infection occurring in four deer. The
      results of the present study demonstrate that post-mortem diagnostics using
      imprint slides and molecular assays are an effective method for detecting
      hemoparasites in organs. 

PMID- 25054501
TI  - Parasite community of Pagrus pagrus (Sparidae) from Rio de Janeiro, Brazil:
      evidence of temporal stability.
AB  - One hundred specimens of Pagrus pagrus were necropsied for parasitological study
      between January and February 2012. These data were compared with data from 90
      specimens that had been examined in the year 2000. The fish were collected from
      Cabo Frio (21-23  degrees  S, 41-45  degrees  W), in the state of Rio de Janeiro,
      Brazil. In the current study a total of 19 parasite species were collected.
      Sixteen of these were collected in the samples of both 2012 and 2000, thus
      totaling 25 parasite species in the two studies. All the results were similar to
      those of the previous study with regard to: dominance of anisakid nematode
      larvae; correlation between abundance of parasites and host body size; absence of
      correlations between the size of parasite infrapopulations and host sex; and
      scarcity of interspecific associations. The only difference between the studies
      was in the abundance values for Anisakidae, which could be correlated with the
      seasonal factor of the collection period, which was concentrated in the summer.
      This is also the period of the South Atlantic Central Water (SACW) phenomenon,
      during which there is greater host reproductive activity. Therefore, significant
      stability of the metazoan community structure of P. pagrus was shown. 

PMID- 25054502
TI  - Histopathologic aspects in Plagioscion squamosissimus (HECKEL, 1940) induced by
      Neoechinorhynchus veropesoi, metacestodes and anisakidae juveniles.
AB  - Plagioscion squamosissimus (Heckel 1840), a fish endemic to the Amazon Basin and
      commonly known as the "silver croaker", plays an important role in the ecology
      and economy of Para State, Brazil. Knowledge of host-parasite relationships is
      important to understanding the role of parasites in the control of natural host
      populations. This work describes histopathological aspects caused by several
      common intestinal parasites found during a helminthological survey of fish in
      northern Brazil. We observed a high prevalence of helminth infection, especially
      by J3 nematode juveniles of the family Anisakidae and metacestodes of the family
      Protocephalidae (both with 100% prevalence). An external capsule surrounded each
      juvenile with numerous juveniles inside sac-like structures formed of connective
      tissue. Inflammation was observed to be caused by infection of metacestodes,
      reaching the intestinal muscularis mucosa. Neoechinorhynchus veropesoi (38%
      prevalence) was found in the small intestine of P. squamosissimus, invading the
      mucosa, submucosa, and internal muscularis of the intestine causing intense
      inflammation. Histopathology of host-parasite relationships in fish has been
      rare, and the pathology of parasites in P. squamosissimus is described herein. 

PMID- 25054503
TI  - Molecular detection of hemotrophic mycoplasmas among domiciled and free-roaming
      cats in Campo Grande, state of Mato Grosso do Sul, Brazil.
AB  - Hemoplasmas are bacteria living in feline red blood cells. Feline hemoplasmosis
      is frequently associated with old male cats that have access to the streets. This
      study aimed to detect the presence of hemoplasma speciess in domiciled and free
      roaming cats in Campo Grande, state of Mato Grosso do Sul (MS), Brazil, using
      molecular techniques. Between January 2013 and April 2013, EDTA-whole blood
      samples were collected from 151 domestic cats (65 free-roaming and 86 domiciled
      cats). Samples were subjected to PCR assays targeting hemoplasmas 16S rRNA,
      followed by sequencing, BLAST analysis and phylogenetic analysis. Results show an
      occurrence of 36.4% for hemoplasmas. Twenty-three cats (15.2%) were positive for
      'Candidatus Mycoplasma haemominutum', 17 (11.2%) for M. haemofelis and 15 (9.9%)
      for 'Candidatus M. turicensis', from PCR. Coinfection by two or three hemoplasmas
      was found in 25 cats (16.6%). No statistically significant difference between
      genders or between lifestyles was observed for the presence of hemoplasmas among
      the cats. Results show different hemoplasma species are present in cat population
      (Campo Grande, MS, Brazil). It is suggested that a differential diagnosis for
      feline hemoplasmosis should be made when cats show nonspecific clinical signs of
      disease with systemic manifestation. 

PMID- 25054504
TI  - Humoral response and evolution of Echinococcus infection in experimentally
      infected sheep.
AB  - There is little information on the humoral response of sheep experimentally
      infected with Echinococcus granulosus. Thus, the objective of this study was to
      evaluate this response and measure its evolution. Doses of 10, 100, 1000 and
      10000 E. granulosus eggs were prepared and inoculated via intraruminal puncture.
      Blood samples were obtained before inoculation and every 48 h after inoculation,
      until they became seropositive. Thereafter, they were taken monthly for the first
      year and then every three months until 1700 days of observation had been
      completed. An ELISA test, with total hydatid fluid antigen, was used for
      immunodiagnosis. The average optical density of the 12 inoculated sheep was found
      to be above the mean cutoff value 10 days after inoculation, went on increasing
      until 180 days after inoculation and remained above the cutoff level until the
      end of the observation period. This confirms that the antibody response of sheep
      to E. granulosus infection occurs before production of hydatid fluid and that
      activation, mobilization and establishment of oncospheres in the tissues
      generates a persistent response from the host's immune system. 

PMID- 25054505
TI  - Parasites of the mutton snapper Lutjanus analis (Perciformes: Lutjanidae) in
      Alagoas, Brazil.
AB  - A parasitological survey was carried out on a sample of sixty mutton snappers
      (Lutjanus analis) that were caught on the coast of Alagoas, northeastern Brazil.
      The parasite diversity and infection levels were low. The ectoparasite Rocinela
      signata Schioedte & Meinert, 1879 (Isopoda: Aegidae), and larvae of two
      endoparasites, Trypanorhyncha gen. sp. and Hysterothylacium sp. (Nematoda:
      Anisakidae), were detected. The significance of these parasites is discussed in
      the context of their transmission pathways and potential impact. 

PMID- 25054506
TI  - Efficacy and safety of topical eprinomectin to control Myocoptes musculinus
      infestation in mice.
AB  - Myocoptes musculinus is the most common fur mite identified among laboratory
      mice; infested mice, in addition to dermatological signs, may also be prone to
      secondary infections, affecting the outcome of a research trial. This trial was
      conducted in order to assess the safety and efficacy of a single topical
      administration of eprinomectin (5mg/kg BW) in a naturally infested laboratory
      mice colony. A safety trial was conducted on 20 uninfested pregnant females
      assigned to two groups, receiving eprinomectin and mineral oil, respectively. The
      mice were examined daily for signs of illness or toxicity; nests were
      individually weighted at 21 and 28 days postpartum. No acute toxicity was
      observed, all treated females gave full term delivery and number and mean weight
      of newborns ranged in the physiological values. To evaluate the efficacy, 20
      naturally infested non-pregnant females were divided into two groups, treated as
      in the safety trial. Animals were observed daily for 15 min until 21 days post
      treatment (DPT) and a "pruritus index" (PI: scratching and gnawing
      acts/mouse/min) was calculated. Pelage examination was performed on DPT 7, 14, 21
      and 50. The "PI" was significantly lower in the treated group and mites were
      eradicated from all infested animals. A single topical administration of
      eprinomectin at a (high) dosage of 5mg/kg BW was safe and effective to control M.
      musculinus in mice. 

PMID- 25054507
TI  - First record of Neobenedenia "melleni"-like species (Monogenea: Capsalidae) in
      Goliath grouper Epinephelus itajara in Brazil.
AB  - Neobenedenia melleni (MacCallum, 1927) (Monogenea) is a pathogen widely spread in
      marine teleost cultures around the world. The present paper recorded this
      parasite species in the Goliath grouper Epinephelus itajara for the first time
      Brazil. The use of freshwater bath for parasite control was successful for the
      Goliath grouper. 

PMID- 25054508
TI  - Detailed morphological description of Habronema clarki Foster & Chitwood, 1937, a
      nematode parasite of capybaras Hydrochoerus hydrochaeris (Linnaeus, 1766) in
      Brazil.
AB  - The genus Habronema has four valid species, of which only two are properly known.
      The present study aimed to describe in detail the morphology of Habronema clarki
      through optical and scanning electron microscopy analyses. Our results showed
      that the labial morphology of this parasite is closer to H. muscae than to H.
      microstoma. Even so, the characteristic pseudolabia and the slightly convex
      border of the dorsal and ventral lips are sufficient to distinguish these
      nematodes. Additional morphological data are presented, thus contributing to the
      knowledge on this little known nematode. In addition, this study provides new
      locality records for this species. 

PMID- 25054509
TI  - Occurrences of anti-Toxoplasma gondii and anti-Neospora caninum antibodies in
      Barbary sheep at Curitiba zoo, southern Brazil.
AB  - Barbary sheep (Ammotragus lervia) have the potential to act as hosts of important
      infectious diseases, particularly zoonoses. Blood samples from 17 Barbary sheep
      at the Curitiba zoo were collected to evaluate occurrences of anti-Toxoplasma
      gondii and anti-Neospora caninum antibodies, tested using the indirect
      immunofluorescence antibody test (IFAT). Anti-T. gondii and anti-N. caninum
      antibodies were detected in 4/17 (23.5%) and 4/17 (23.5%) samples, respectively.
      The present study has shown that Barbary sheep at Curitiba zoo were exposed to T.
      gondii and N. caninum and therefore may act as intermediate hosts, spreading
      toxoplasmosis and neosporosis within and between species in shared areas. 

PMID- 25054510
TI  - First records of chewing lice (Phthiraptera: Menoponidae) in Pacific migratory
      shorebirds wintering in Ecuador.
AB  - Chewing lice were collected from small shorebirds (Charadriformes: Scolopacidae)
      overwintering in foraging grounds of coastal Ecuador. On 27 occasions at least
      one louse (3.7%) was collected from six host species. Based on external
      morphological characters, at least two species of chewing lice could be
      preliminary identified (family: Menoponidae), including Actornithophilus umbrinus
      (Burmeister, 1842) and Austromenopon sp. A. umbrinus was found in the Western
      Sandpiper (Calidris mauri), Least Sandpiper (C. minutilla), Stilt Sandpiper (C.
      himantopus), Semipalmated Plover (Charadrius semipalmatus) and Wilson's phalarope
      (Phalaropus tricolor), while Austromenopon sp. is presumably the first record
      collected from the Surfbird (Aphriza virgata). These findings indicate that the
      distribution of these chewing lice species covers at least the regions around the
      equator (latitude 0 degrees ) until the Arctic in the north, but probably also
      includes the entire winter distribution area of the host species. This is the
      first study of chewing lice from Ecuador's mainland coast and more research is
      required to understand the host-parasite ecology and ectoparasitic infection in
      shorebirds stopping over the region. 

PMID- 25054511
TI  - Free-living ixodid ticks in an urban Atlantic Forest fragment, state of Rio de
      Janeiro, Brazil.
AB  - As a consequence of the importance of ticks in forests in protected areas, was
      conducted survey of species of free-living ticks in the Natural Park Municipal
      Curio, state of Rio de Janeiro, Brazil. Monthly samples were taken by dragging
      method, dry ice traps and visual search in two transects. Adults and nymphs of
      Amblyomma cajennense (n= 147), Amblyomma brasiliense (n= 4) and Amblyomma parvum
      (n= 1) were collected. This is the first occurrence of A. parvum in the state. No
      correlation was found between the abundance of stages of A. cajennense and
      rainfall, temperature and relative humidity. The highest abundances of adults
      were in the months of January and May, and nymphs in September and October. The
      low diversity of parasites on Curio Park can be attributed to the proximity of
      households with pets, which would also explain the higher abundance of A.
      cajennense that is commonly found in areas impacted by anthropogenic pressure. 

PMID- 25054512
TI  - Detection of Leishmania infantum in Lutzomyia longipalpis captured in Campo
      Grande, MS.
AB  - Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania
      (Ross, 1903) and is the focus of considerable attention in human and veterinary
      medicine. In the city of Campo Grande, MS, the causative agent of visceral
      leishmaniasis is Leishmania infantum (= L. chagasi) primary vector, comprising
      approximately 92.9% of the local sandfly population, is Lutzomyia longipalpis.
      The aim of this work was to compare real-time PCR with PCR as a tool for the
      detection of the kinetoplast DNA (kDNA) of L. infantum in sandflies. Sandflies of
      this species were caught, and a total of 38 samples with 1-4 individuals in each
      sample were obtained; these were distributed across 13 districts and divided
      between seven urban areas of the city of Campo Grande, MS. Three positive samples
      were found by PCR and, when using real-time PCR, this was able to detect the
      presence of this agent in 6 of the 13 districts sampled, which were all located
      on the outskirts of the city, where indicates the greater enzootic potential of
      these regions, as they are closer to natural forest reserves. We conclude that
      real-time PCR can be used for epidemiological studies of L. infantum. 

PMID- 25054513
TI  - New record of Pelecitus sp. (Nematoda, Onchocercidae) as a parasite of Athene
      cunicularia (Strigiformes, Strigidae) in southeastern Brazil.
AB  - The aim of this study was to report the burrowing owl Athene cunicularia as a new
      host for the filarid nematode Pelecitus sp. in southeastern Brazil for the first
      time, as well as reporting the occurrence of this nematode species in the body
      cavity, near the cervical air sac and lung region. This study contributes towards
      knowledge of parasitism in Brazilian wild birds and an anatomical region of the
      host as an infection site for Pelecitus sp. 

PMID- 25054514
TI  - Rhipicephalus sanguineus sensu lato (Ixodidae) in synantropic rodents in Rio
      Grande do Sul, Brazil.
AB  - Rhipicephalus sanguineus, the brown dog tick, is responsible for maintaining and
      transmitting various pathogens, both in animals and human beings, and it is of
      great sanitary importance. This communication reports the first occurrence of
      Rhipicephalus sanguineus sensu lato parasitizing Rattus norvegicus in the state
      of Rio Grande do Sul, Brazil, and it is also the first record of this tick
      species parasitizing Rattus rattus in Brazil. The rodents were captured from the
      port area, located in the city of Pelotas, Rio Grande do Sul, Brazil. We
      collected 6 larvae of this tick species from 2 male R. rattus individuals, and 3
      larvae from 2 female R. norvegicus individuals; parasitized specimens of both
      rodent species were captured from different sites within the experimental area.
      This record broadens the number of Rhipicephalus sanguineus sensu lato hosts in
      urban areas, indicating the need for continued monitoring on population density
      for both R. sanguineus and synanthropic rodents. 

PMID- 25054515
TI  - Eimeria infections in goats in Southern Portugal.
AB  - Coccidiosis caused by Eimeria species is a major form of intestinal infection
      affecting intensively and semi-intensively reared goats. The province of Alentejo
      is the main goat-producing area in Portugal. Therefore, all 15 Serpentina goat
      farms in Alentejo were analyzed regarding the occurrence and diversity of Eimeria
      species. Fecal samples obtained from 144 animals (52.1% dairy goats, 47.9% pre
      pubertal goats) were examined using the modified McMaster technique to determine
      the number of oocysts per gram of feces. Eimeria spp. oocysts were present in
      98.61% of the fecal samples and, overall, nine different Eimeria species were
      identified. The most prevalent species were E. ninakohlyakimovae (88%) and E.
      arloingi (85%), followed by E. alijevi (63%) and E. caprovina (63%). The average
      number of oocysts shed was significantly lower in dairy goats than in pre-adult
      animals. Astonishingly, no clinical signs of coccidiosis were observed in any of
      the animals examined, even though they were shedding high numbers of oocysts and
      were infected with highly pathogenic species. Thus, implementation of routine
      diagnostic investigation of the occurrence and diversity of caprine Eimeria
      species may be a useful tool for determination and better understanding of their
      potential economic impact on goat herds in southern Portugal. 

PMID- 25054517
TI  - Importance of rigorous in vitro evaluation of prospective cell binding aptamers.
AB  - Hitherto, several aptamers have been selected against cell surface molecules. The
      use of these aptamers for in vivo applications requires the prior in-depth in
      vitro evaluation of cell specific binding. Here, we demonstrate the in vitro
      tests, which are imperatively necessary to evaluate aptamers prior to in vivo
      applications. Exemplarily, the target binding of a chemically synthesized model
      aptamer containing phosphorothioate linkages was tested after the induction of
      the target protein expression on the cell surface by using flow cytometry.
      Furthermore, different cell types were used to compare the binding of the
      aptamer. Different single stranded DNA oligonucleotides were selected as negative
      controls to evaluate sequence specific binding of the aptamer to the cells. In
      further experiments, the aptamer binding to the target cells was determined in a
      mixture containing human plasma and peripheral blood cells to simulate the
      binding of the aptamer to target cells in human whole blood. In this study, we
      demonstrated the compelling necessity of the in vitro binding tests with the
      selected aptamers using target and non-target cells, the use of appropriate
      nonsense aptamers to validate the sequence specific binding of aptamers, and the
      evaluation of target binding in human plasma containing blood proteins and cells.
      Thus, we recommend the use of described methods to validate the target specific
      binding of newly selected aptamers prior to in vivo applications. 

PMID- 25054516
TI  - Evidence of Borrelia in wild and domestic mammals from the state of Minas Gerais,
      Brazil.
AB  - The main of the study was to evaluate the presence of Borrelia burgdorferi
      infection in domestic and wild vertebrates and ectoparasites in endemic areas
      from the state of Minas Gerais, Brazil. A total of 445 serum samples were
      examined by ELISA, which used the Borrelia burgdorferi strain G39/40 U.S. source
      and 3,821 tick samples were tested by polymerase chain reaction (PCR). B.
      burgdorferi antibodies were found in 30 serum samples (6.74%); three in
      marsupials (7.69%), three in rodents (2.80%), nine in dogs (6.25%), and 15 in
      horses (9.68%). Nested-PCR performed in DNA samples obtained from collected ticks
      demonstrated negative results. Although attempts to amplify B. burgdorferi DNA
      from ticks had been not successful, the presence of seroreactive vertebrates
      suggests the possibility the Borrelia species circulating in these regions.
      Further research is required to provide information on the presence of Borrelia
      in Brazilian territory and its association with Baggio-Yoshinari syndrome. 

PMID- 25054519
TI  - Palladium-catalyzed gamma-selective arylation of zincated Boc-allylamines.
AB  - The regio- and diastereoselective arylation of Boc-protected allylamines was
      performed via a one-pot lithiation/transmetalation to zinc/cross-coupling
      sequence, through an appropriate choice of a phosphine ligand. A variety of gamma
      arylated products were obtained in moderate to good yield, and the products could
      be directly transformed into valuable gamma-arylamines and beta-aryl aldehydes. 

PMID- 25054518
TI  - Toxicological and pharmacokinetic properties of QPI-1007, a chemically modified
      synthetic siRNA targeting caspase 2 mRNA, following intravitreal injection.
AB  - We report the toxicological and pharmacokinetic properties of the synthetic,
      small interfering RNA (siRNA), QPI-1007, following intravitreal administration.
      QPI-1007 is a chemically modified siRNA designed to act via the RNA interference
      (RNAi) pathway to temporarily inhibit expression of the caspase 2 protein and is
      being developed as a neuroprotectant for the treatment of nonarteritic anterior
      ischemic optic neuropathy and other optic neuropathies such as glaucoma that
      result in the death of retinal ganglion cells. The half-life of QPI-1007 in the
      vitreous and retina/choroid in the Dutch Belted rabbit was about 2 days, and
      there was no sign of accumulation after repeated administrations at either 2- or
      4-week dosing intervals in the rabbit. QPI-1007 was well tolerated in Dutch
      Belted rabbits following single or repeated intravitreal administrations of up to
      11 doses over 9 months. Test-article-related effects were limited to the eyes,
      with minimal to mild vitreal cellular infiltration being the major finding, which
      was reversible. In repeated-dose studies, a modest reduction in B-wave amplitude
      obtained by electroretinography was observed in animals treated with the highest
      dose level tested (3 mg, which is equivalent to a 12 mg/eye human dose) that was
      not considered to be clinically meaningful. Administration in the rat of either a
      single bolus intravenous (i.v.) injection of 100 mg/kg or daily bolus i.v.
      injections of 75 mg/kg/day for 28 days failed to elicit any macroscopic or
      microscopic changes, suggesting a low risk for systemic toxicity. QPI-1007 was
      negative in three genetic toxicity studies. Overall, the nonclinical studies
      support the further development of QPI-1007.

PMID- 25054521
TI  - Highly cited articles in Physics in Medicine and Biology.

PMID- 25054522
TI  - Management of acute hyperglycemic emergencies: focus on diabetic ketoacidosis.

PMID- 25054524
TI  - Atrial fibrillation in the elderly: management strategies to achieve performance
      measures.

PMID- 25054525
TI  - Evaluation of the use of a stabilization device to improve the quality of care in
      patients with peripherally inserted central catheters.
AB  - OBJECTIVES: This project evaluated the implementation of use of the StatLock
      stabilization device (Bard Access Systems, Inc, Salt Lake City, Utah) for
      peripherally inserted central catheters (PICCs) in pediatric cardiology patients.
      The aim was to implement the use of the StatLock device and evaluate its effects
      on the following 4 outcomes: incidence of dislodgement, infection, catheter dwell
      time, and the number of catheter replacements. The primary goal was to determine
      whether the StatLock device offered advantages over tape and sutures. METHODS: A
      quality improvement design was used to evaluate whether the use of the StatLock
      stabilization device for PICC securement on 30 pediatric cardiology patients
      decreased the number of PICC complications compared with 30 historical comparison
      patients. RESULTS: The comparison group had a significantly higher number of
      catheter dislodgements (n = 16; 59.3%) than the StatLock group (n = 8; 30.8%; P =
      .035). The comparison group did not have a significantly higher number of
      catheter replacements (n = 16; 59.3%) than the StatLock group (n = 10; 34.5%; P =
      .10). No significant differences were found in the rate of infection or in the
      catheter dwell time between the 2 groups (StatLock group, mean +/- SD = 33.13 +/-
      22.71 days; comparison group, mean +/- SD = 28.10 +/- 24.83 days; P > .20).
      CONCLUSIONS: Use of the StatLock device resulted in better outcomes when compared
      with the use of sutures, and it provided a more effective way to stabilize and
      secure PICCs.

PMID- 25054526
TI  - Hyperglycemia after cardiac surgery: improving a quality measure.
AB  - BACKGROUND: The Surgical Care Improvement Project #4 (SCIP#4) performance measure
      is used to evaluate achievement of target blood glucose control after cardiac
      surgery. OBJECTIVES: The purpose of this study was to identify patient
      characteristics and outcomes in patients undergoing cardiac surgery who met the
      SCIP#4 performance measure versus those who did not. METHODS: A retrospective
      case-control design was used. RESULTS: Preoperative hemoglobin A1C (HbA1C) level
      and history of diabetes were 2 major risk factors for failing to meet the SCIP#4
      measure. A trend toward a longer length of stay was observed, mortality was 3
      times more prevalent, and renal failure was 4 times more frequent in patients who
      did not meet the SCIP#4 quality measure. CONCLUSIONS: Not meeting the SCIP#4
      measure is associated with adverse outcomes. History of diabetes and preoperative
      HbAIC level should be considered when evaluating strategies for managing
      postsurgical hyperglycemia.

PMID- 25054527
TI  - Differential diagnoses for select critical care symptoms.

PMID- 25054528
TI  - Differential diagnosis: correctly putting the pieces of the puzzle together.
AB  - Each day, we generate hypotheses about our environment-our perceptions of people,
      our expectations of events, and our interpretation of images. These hypotheses
      provide a framework by which we interpret our experiences. The same is true for
      differential diagnosis by which health care practitioners develop hypotheses or
      diagnoses from a set of cues provided during an encounter with a patient. For
      clinicians to be successful at differential diagnosis, they must use a
      multidimensional and complex process involving nonanalytic and analytic cognitive
      processes and metacognition-thinking about thinking. Our conclusions, however,
      can lead to errors in diagnosis. Many of these errors are due to errors in
      cognition. The purpose of this article is to discuss this complex process,
      identify common errors in cognition, and offer strategies to prevent these common
      errors in differential diagnosis.

PMID- 25054529
TI  - Fever in acute and critical care: a diagnostic approach.
AB  - Determining the underlying cause of a fever can be a daunting task. Multiple
      reasons have been found for a patient to have a fever, but the use of an
      organized approach will assist clinicians in reaching a correct diagnosis. The
      first step in this process is a complete assessment, including a thorough
      physical assessment and an evaluation of the history of present illness as well
      as a detailed review of all the patient's medications. Infection should always be
      a primary consideration for the cause of a fever. Evaluating each body system can
      match symptoms with a possible cause for fever, and proper testing and imaging
      can be pursued. Noninfectious causes of fever need to be included in the
      differential diagnostic process. This article provides an analytic approach to
      fever in adult patients in the acute and critical care environment.

PMID- 25054531
TI  - Acute nontraumatic weakness: overview of central nervous system differential
      diagnosis.
AB  - Depending on the causative agent, the differential diagnosis for acute
      nontraumatic weakness presentation can range from life threatening to trivial.
      Practitioners' comfort and experience with the rapid identification and
      evaluation of presenting neurological deficits vary widely. Given this fact and
      the reality that neurological presentation of weakness is common, the potential
      for missed diagnosis increases. To enhance knowledge of potentially life
      threatening or morbidity-inducing complications, this article provides a
      systematic framework for physical and diagnostic evaluation of the most common
      differentials for acute causes of nontraumatic weakness.

PMID- 25054532
TI  - Abdominal pain: an approach to a challenging diagnosis.
AB  - Acute abdominal pain represents the cardinal symptom of a large number of intra
      abdominal pathologies. Because of multiple organ systems, varied pathology from
      life threatening to benign, and differences in presentation related to sex and
      age, identifying a final diagnosis is a challenge. The clinician's goal for
      patients with acute abdominal pain is to rapidly identify whether the underlying
      cause requires an urgent or immediate surgical intervention. By developing a
      systematic approach to evaluating patients with abdominal pain, clinicians can
      generate a differential diagnosis to ensure appropriate treatment and improved
      patient outcomes. The purpose of this article is to provide clinicians with a
      framework for evaluating the complaint of acute abdominal pain and recognizing
      patients who require expedited evaluation. 

PMID- 25054533
TI  - Chest pain: a time for concern?
AB  - When a patient complains of chest pain, the first priority is to establish
      whether the situation is life threatening. Life-threatening differential
      diagnoses that clinicians must consider include acute coronary syndrome, cardiac
      tamponade, pulmonary embolus, aortic dissection, and tension pneumothorax.
      Nonthreatening causes of chest pain that should be considered include spontaneous
      pneumothorax, pleural effusion, pneumonia, valvular diseases, gastric reflux, and
      costochondritis. The challenge for clinicians is not to be limited by
      "satisfaction of search" and fail to consider important differential diagnoses.
      The challenge, however, can be met by developing a systematic method to assess
      chest pain that will lead to the appropriate diagnosis and appropriate treatment
      plan.

PMID- 25054534
TI  - The challenge of diagnosing dyspnea.
AB  - Dyspnea is a subjective and nonspecific symptom, yet very distressing for those
      who experience it. Acute onset dyspnea and exacerbation of chronic dyspnea from
      heart or lung disease significantly add to the number of emergency department
      visits and inpatient admissions. Although dyspnea may appear to be a simple
      condition to evaluate and manage, it is actually complex in description and
      quality. As such, dyspnea is the first symptom of many diseases. The onset of
      dyspnea can be due to a new acute disease, the exacerbation of an existing
      chronic illness, or a new disease compounding a chronic illness. Finding the
      cause of dyspnea is generally more difficult than it originally may appear.
      Therefore, the purpose of this article is to discuss the differential diagnoses
      associated with dyspnea.

PMID- 25054535
TI  - Budgeting nursing time to support unit-based clinical inquiry.

PMID- 25054536
TI  - Influence of calcium abnormalities on the ECG.

PMID- 25054537
TI  - TMSCl-mediated synthesis of alpha,beta-unsaturated amides via C-C bond cleavage
      and C-N bond formation of propargyl alcohols with trimethylsilyl azide.
AB  - A new method with high efficiency for the synthesis of alpha,beta-unsaturated
      amides from the easily prepared propargyl alcohols and TMSN3 using TMSCl as an
      acid promoter is developed. A wide variety of alpha,beta-unsaturated amides were
      produced in moderate to excellent yields. Mechanistic studies indicate that this
      transformation involves TMSCl-mediated allenylazide intermediate formation, C-C
      bond cleavage, and C-N bond formation. Significantly, this reaction shows good
      functional group compatibility and high regioselectivity, with a relatively short
      reaction time and inexpensive reagents. 

PMID- 25054538
TI  - A change in the editorial office: farewell from Catherine M. Bollard.

PMID- 25054540
TI  - Modelling fire frequency in a Cerrado savanna protected area.
AB  - Covering almost a quarter of Brazil, the Cerrado is the world's most biologically
      rich tropical savanna. Fire is an integral part of the Cerrado but current land
      use and agricultural practices have been changing fire regimes, with undesirable
      consequences for the preservation of biodiversity. In this study, fire frequency
      and fire return intervals were modelled over a 12-year time series (1997-2008)
      for the Jalapao State Park, a protected area in the north of the Cerrado, based
      on burned area maps derived from Landsat imagery. Burned areas were classified
      using object based image analysis. Fire data were modelled with the discrete
      lognormal model and the estimated parameters were used to calculate fire
      interval, fire survival and hazard of burning distributions, for seven major land
      cover types. Over the study period, an area equivalent to four times the size of
      Jalapao State Park burned and the mean annual area burned was 34%. Median fire
      intervals were generally short, ranging from three to six years. Shrub savannas
      had the shortest fire intervals, and dense woodlands the longest. Because fires
      in the Cerrado are strongly responsive to fuel age in the first three to four
      years following a fire, early dry season patch mosaic burning may be used to
      reduce the extent of area burned and the severity of fire effects. 

PMID- 25054539
TI  - Disproportionate contribution of right middle lobe to emphysema and gas trapping
      on computed tomography.
AB  - RATIONALE: Given that the diagnosis of chronic obstructive pulmonary disease
      (COPD) relies on demonstrating airflow limitation by spirometry, which is known
      to be poorly sensitive to early disease, and to regional differences in
      emphysema, we sought to evaluate individual lobar contributions to global
      spirometric measures. METHODS: Subjects with COPD were compared with smokers
      without airflow obstruction, and non-smokers. Emphysema (% low attenuation area,
      LAAinsp<-950 HU, at end-inspiration) and gas trapping (%LAAexp<-856 HU at end
      expiration) on CT were quantified using density mask analyses for the whole lung
      and for individual lobes, and distribution across lobes and strength of
      correlation with spirometry were compared. RESULTS: The right middle lobe had the
      highest %LAAinsp<-950 HU in smokers and controls, and the highest %LAAexp<-856 HU
      in all three groups. While RML contributed to emphysema and gas trapping
      disproportionately to its relatively small size, it also showed the least
      correlation with spirometry. There was no change in correlation of whole lung CT
      metrics with spirometry when the middle lobe was excluded from analyses.
      Similarly, RML had the highest %LAAexp<-856 HU while having the least correlation
      with spirometry. CONCLUSIONS: Because of the right middle lobe's disproportionate
      contribution to CT-based emphysema measurements, and low contribution to
      spirometry, longitudinal studies of emphysema progression may benefit from
      independent analysis of the middle lobe in whole lung quantitative CT
      assessments. Our findings may also have implications for heterogeneity
      assessments and target lobe selection for lung volume reduction. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00608764.

PMID- 25054541
TI  - On the validity of using increases in 5-year survival rates to measure success in
      the fight against cancer.
AB  - BACKGROUND: The 5-year survival rate of cancer patients is the most commonly used
      statistic to reflect improvements in the war against cancer. This idea, however,
      was refuted based on an analysis showing that changes in 5-year survival over
      time bear no relationship with changes in cancer mortality. METHODS: Here we show
      that progress in the fight against cancer can be evaluated by analyzing the
      association between 5-year survival rates and mortality rates normalized by the
      incidence (mortality over incidence, MOI). Changes in mortality rates are caused
      by improved clinical management as well as changing incidence rates, and since
      the latter can mask the effects of the former, it can also mask the correlation
      between survival and mortality rates. However, MOI is a more robust quantity and
      reflects improvements in cancer outcomes by overcoming the masking effect of
      changing incidence rates. Using population-based statistics for the US and the
      European Nordic countries, we determined the association of changes in 5-year
      survival rates and MOI. RESULTS: We observed a strong correlation between changes
      in 5-year survival rates of cancer patients and changes in the MOI for all the
      countries tested. This finding demonstrates that there is no reason to assume
      that the improvements in 5-year survival rates are artificial. We obtained
      consistent results when examining the subset of cancer types whose incidence did
      not increase, suggesting that over-diagnosis does not obscure the results.
      CONCLUSIONS: We have demonstrated, via the negative correlation between changes
      in 5-year survival rates and changes in MOI, that increases in 5-year survival
      rates reflect real improvements over time made in the clinical management of
      cancer. Furthermore, we found that increases in 5-year survival rates are not
      predominantly artificial byproducts of lead-time bias, as implied in the
      literature. The survival measure alone can therefore be used for a rough
      approximation of the amount of progress in the clinical management of cancer, but
      should ideally be used with other measures.

PMID- 25054543
TI  - The energy-down-shift effect of Cd(0.5)Zn(0.5)S-ZnS core-shell quantum dots on
      power-conversion-efficiency enhancement in silicon solar cells.
AB  - We found that Cd0.5Zn0.5S-ZnS core (4.2 nm in diameter)-shell (1.2 nm in
      thickness) quantum dots (QDs) demonstrated a typical energy-down-shift (2.76-4.96
      -> 2.81 eV), which absorb ultra-violet (UV) light (250-450 nm in wavelength) and
      emit blue visible light (~442 nm in wavelength). They showed the quantum yield of
      ~80% and their coating on the SiNX film textured p-type silicon solar-cells
      enhanced the external-quantum-efficiency (EQE) of ~30% at 300-450 nm in
      wavelength, thereby enhancing the short-circuit-current-density (JSC) of ~2.23 mA
      cm(-2) and the power-conversion-efficiency (PCE) of ~1.08% (relatively ~6.04%
      increase compared with the reference without QDs for p-type silicon solar-cells).
      In particular, the PCE peaked at a specific coating thickness of the Cd0.5Zn0.5S
      ZnS core-shell QD layer; i.e., the 1.08% PCE enhancement at the 8.8 nm thick QD
      layer. 

PMID- 25054542
TI  - Direct interrogation of DNA content distribution in nanoparticles by a novel
      microfluidics-based single-particle analysis.
AB  - Nonviral gene delivery holds great promise not just as a safer alternative to
      viral vectors in traditional gene therapy applications, but also for regenerative
      medicine, induction of pluripotency in somatic cells, and RNA interference for
      gene silencing. Although it continues to be an active area of research, there
      remain many challenges to the rational design of vectors. Among these, the
      inability to characterize the composition of nanoparticles and its distribution
      has made it difficult to probe the mechanism of gene transfection process, since
      differences in the nanoparticle-mediated transfection exist even when the same
      vector is used. There is a lack of sensitive methods that allow for full
      characterization of DNA content in single nanoparticles and its distribution
      among particles in the same preparation. Here we report a novel spectroscopic
      approach that is capable of interrogating nanoparticles on a particle-by-particle
      basis. Using PEI/DNA and PEI-g-PEG/DNA nanoparticles as examples, we have shown
      that the distribution of DNA content among these nanoparticles was relatively
      narrow, with the average numbers of DNA of 4.8 and 6.7 per particle,
      respectively, in PEI/DNA and PEI-g-PEG/DNA nanoparticles. This analysis enables a
      more accurate description of DNA content in polycation/DNA nanoparticles. It
      paves the way toward comparative assessments of various types of gene carriers
      and provides insights into bridging the efficiency gap between viral and nonviral
      vehicles. 

PMID- 25054544
TI  - High performance asymmetrical push-pull small molecules end-capped with
      cyanophenyl for solution-processed solar cells.
AB  - Two novel asymmetrical push-pull small molecules have been synthesized
      successfully, consisting of triphenylamine and diketopyrrolopyrrole as a
      fundamental dipolar D-pi-A structure with ethynylbenzene as the pi-bridge.
      TPATDPPCN end-capped with cyanophenyl exhibits a low optical band gap of 1.65 eV,
      and an impressive PCE of 5.94% has been achieved. 

PMID- 25054545
TI  - [A new flexible endoscopy-system for the transoral resection of head and neck
      tumors].
AB  - INTRODUCTION: Within the last years transoral robotic surgery (TORS) with
      endoscopic visualization and surgery has gained importance in the resection of
      head and neck tumors and is an alternative to transoral laser microsurgery. The
      further development of transoral endoscopic systems should enhance the surgical
      options and reduce the surgery related morbidity. Thus, we evaluated a new
      flexible endoscopy system in cadaver -dissections. METHODS: In March 2014 we
      performed all standard procedures of transoral tumor surgery in the oropharynx,
      hypopharynx and larynx in 3 fresh cadaveric specimens using the Medrobotics
      Flex((r)) System. In a prospective study we analyzed exposure, -visualization,
      accessibility and resectability of the respective -anatomic regions. RESULTS: All
      relevant anatomic structures of the pharynx and supraglottic region could be well
      exposed, visualized and accessed. Tonsillectomies and resections of the soft
      palate as well as the base of tongue could be performed easily. Supraglottic
      resections were possible with a good visualization. The piriform sinus could be
      exposed, and controlled tissue resections were possible-. The vocal cords were
      accessible and cordectomies could be performed. CONCLUSION: By combining a robot
      assisted flexible endoscope with flexible instruments the Flex system facilitates
      the visualization and accessibility of all relevant anatomic structures of
      pharynx and larynx. It is a promising system which now has to be further
      evaluated in clinical trials.

PMID- 25054546
TI  - Prevalence and determinants of adult under-nutrition in Botswana.
AB  - BACKGROUND: To estimate the prevalence and determinants of adult under-nutrition
      in Botswana. METHODS: A cross-sectional survey was conducted where a nationally
      representative sample of people aged 20 to 49 years was used for the analysis.
      The outcome measure of under-nutrition was measured as BMI<18.5 kg/m2. RESULTS:
      Of the total sample, 19.5% of males and 10.1% of females were underweight
      (BMI<18.5 kg/m2). The wealth index showed that 30.9% of the adult population with
      low a BMI belongs to the poorest 20% of the households while only 9.6% comprised
      of the richest 20% of the households. Results from logistic regression analysis
      indicated that both adult men and women who had no education and belonged to the
      low socioeconomic group had a statistically significant association with low BMI.
      Among the female adult population, being young and not having watched TV at least
      once a week were significantly associated with low BMI. For the male adult
      population, being unmarried was significantly associated with low BMI.
      CONCLUSIONS: Programme interventions aimed at improving the nutritional status of
      adults can use these findings to make appropriate policy, to establish baselines
      and study nutritional changes over time and its covariates.

PMID- 25054547
TI  - Characterization of a novel BCHE "silent" allele: point mutation (p.Val204Asp)
      causes loss of activity and prolonged apnea with suxamethonium.
AB  - Butyrylcholinesterase deficiency is characterized by prolonged apnea after the
      use of muscle relaxants (suxamethonium or mivacurium) in patients who have
      mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular
      block after administration of suxamethonium leading to the discovery of a novel
      BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and
      molecular dynamics were undertaken to understand how this mutation disrupts the
      catalytic triad and determines a "silent" phenotype. Low activity of patient
      plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine,
      and values of dibucaine and fluoride numbers fit with heterozygous atypical
      silent genotype. Electrophoretic analysis of plasma BChE of the proband and his
      mother showed that patient has a reduced amount of tetrameric enzyme in plasma
      and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin
      conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly
      p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate.
      Both catalytic parameters Km = 265 uM for BTC, two times higher than that of the
      atypical enzyme, and a low Vmax are consistent with the absence of activity
      against suxamethonium. Molecular dynamic (MD) simulations showed that the overall
      effect of the mutation p.Val204Asp is disruption of hydrogen bonding between
      Gln223 and Glu441, leading Ser198 and His438 to move away from each other with
      subsequent disruption of the catalytic triad functionality regardless of the type
      of substrate. MD also showed that the enzyme volume is increased, suggesting a
      pre-denaturation state. This fits with the reduced concentration of
      p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non
      detectable fast moving-bands on electrophoresis gels. 

PMID- 25054548
TI  - Overview photography and short-term mole monitoring in patients taking a BRAF
      inhibitor.

PMID- 25054549
TI  - Voluntary climate change mitigation actions of young adults: a classification of
      mitigators through latent class analysis.
AB  - Encouraging individuals to take action is important for the overall success of
      climate change mitigation. Campaigns promoting climate change mitigation could
      address particular groups of the population on the basis of what kind of
      mitigation actions the group is already taking. To increase the knowledge of such
      groups performing similar mitigation actions we conducted a population-based
      cross-sectional study in Finland. The study population comprised 1623 young
      adults who returned a self-administered questionnaire (response rate 64%). Our
      aims were to identify groups of people engaged in similar climate change
      mitigation actions and to study the gender differences in the grouping. We also
      determined if socio-demographic characteristics can predict group membership. We
      performed latent class analysis using 14 mitigation actions as manifest
      variables. Three classes were identified among men: the Inactive (26%), the Semi
      active (63%) and the Active (11%) and two classes among women: the Semi-active
      (72%) and the Active (28%). The Active among both genders were likely to have
      mitigated climate change through several actions, such as recycling, using
      environmentally friendly products, preferring public transport, and conserving
      energy. The Semi-Active had most probably recycled and preferred public transport
      because of climate change. The Inactive, a class identified among men only, had
      very probably done nothing to mitigate climate change. Among males, being single
      or divorced predicted little involvement in climate change mitigation. Among
      females, those without tertiary degree and those with annual income ?>=16801 were
      less involved in climate change mitigation. Our results illustrate to what extent
      young adults are engaged in climate change mitigation, which factors predict
      little involvement in mitigation and give insight to which segments of the public
      could be the audiences of targeted mitigation campaigns. 

PMID- 25054552
TI  - Breastfeeding trends in Cambodia, and the increased use of breast-milk substitute
      why is it a danger?
AB  - A cross-sectional analysis of the Cambodia Demographic Health Surveys from 2000,
      2005 and 2010 was conducted to observe the national trends in infant and young
      child feeding practices. The results showed that rates of exclusive breastfeeding
      among infants aged 0-5.9 months have increased substantially since 2000,
      concurrent with an increase in the rates of early initiation of breastfeeding and
      a reduction in the giving of pre-lacteal feeds. However, the proportion of
      infants being fed with breast-milk substitutes (BMS) during 0-5.9 months doubled
      in 5 years (3.4% to 7.0%) from 2000 to 2005, but then did not increase from 2005,
      likely due to extensive public health campaigns on exclusive breastfeeding. BMS
      use increased among children aged 6-23.9 months from 2000 to 2010 (4.8% to 9.3%).
      26.1% of women delivering in a private clinic provided their child with breast
      milk substitute at 0-5.9 months, which is five times more than women delivering
      in the public sector (5.1%), and the greatest increase in bottle use happened
      among the urban poor (5.8% to 21.7%). These findings are discussed with reference
      to the increased supply and marketing of BMS that is occurring in Cambodia. 

PMID- 25054550
TI  - Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy
      school-aged children and throughout adulthood? Evidence from clinical trials.
AB  - Long-chain (LC) omega-3 PUFA derived from marine sources may play an important
      role in cognitive performance throughout all life stages. Docosahexaenoic acid
      (DHA), the dominant omega-3 in the brain, is a major component of neuronal cell
      membranes and affects various neurological pathways and processess. Despite its
      critical role in brain function, human's capacity to synthesize DHA de novo is
      limited and its consumption through the diet is important. However, many
      individuals do not or rarely consume seafood. The aim of this review is to
      critically evaluate the current evidence from randomised controlled trials (RCT)
      in healthy school-aged children, younger and older adults to determine whether
      consumption of LC omega-3 PUFA improves cognitive performance and to make
      recommendations for future research. Current evidence suggests that consumption
      of LC omega-3 PUFA, particularly DHA, may enhance cognitive performance relating
      to learning, cognitive development, memory and speed of performing cognitive
      tasks. Those who habitually consume diets low in DHA, children with low literacy
      ability and malnourished and older adults with age-related cognitive decline and
      mild cognitive impairment seem to benefit most. However, study design limitations
      in many RCTs hamper firm conclusions. The measurement of a uniform biomarker,
      e.g., % DHA in red blood cells, is essential to establish baseline DHA-status, to
      determine targets for cognitive performance and to facilitate dosage
      recommendations. It is recommended that future studies be at least 16 weeks in
      duration, account for potential interaction effects of gender, age and
      apolipoprotein E genotype, include vegan/vegetarian populations, include measures
      of speed of cognitive performance and include brain imaging technologies as
      supportive information on working mechanisms of LC omega-3 PUFA. 

PMID- 25054554
TI  - Heritability and evolutionary potential in thermal tolerance traits in the
      invasive Mediterranean cryptic species of Bemisia tabaci (Hemiptera:
      Aleyrodidae).
AB  - With advancing global climate change, the analysis of thermal tolerance and
      evolutionary potential is important in explaining the ecological adaptation and
      changes in the distribution of invasive species. To reveal the variation of heat
      resistance and evolutionary potential in the invasive Mediterranean cryptic
      species of Bemisia tabaci, we selected two Chinese populations-one from Harbin, N
      China, and one from Turpan, S China-that experience substantial heat and cold
      stress and conducted knockdown tests under static high- and low-temperature
      conditions. ANOVAs indicated significant effects of populations and sex on heat
      knockdown time and chill coma recovery time. The narrow-sense heritability (h2)
      estimates of heat tolerance based on a parental half-sibling breeding design
      ranged from 0.47 +/- 0.03 to 0.51 +/- 0.06, and the estimates of cold tolerance
      varied from 0.33 +/- 0.07 to 0.36 +/- 0.06. Additive genetic variances were
      significantly different from zero for both heat and cold tolerance. These results
      suggest that invasive B. tabaci Mediterranean cryptic species possesses a strong
      ability to respond to thermal selection and develops rapid resistance to climate
      change.

PMID- 25054553
TI  - Caffeine ingestion after rapid weight loss in judo athletes reduces perceived
      effort and increases plasma lactate concentration without improving performance.
AB  - The objective of this study was to examine the effect of caffeine on judo
      performance, perceived exertion, and plasma lactate response when ingested during
      recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5
      day rapid weight loss procedure to reduce their body weight by ~5%. After weigh
      in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour
      of this "loading period", subjects ingested a capsule containing either caffeine
      (6 mg.kg-1) or placebo. One hour later, participants performed three bouts of a
      judo fitness test with 5-min recovery periods. Perceived exertion and plasma
      lactate were measured before and immediately after each test bout. Body weight
      was reduced in both caffeine and placebo conditions after the weight loss period
      (-3.9% +/- 1.6% and -4.0% +/- 2.3% from control, respectively, p < 0.05). At
      three hours after weigh-in, body weight had increased with both treatments but
      remained below the control (-3.0% +/- 1.3% and -2.7% +/- 2.2%). There were no
      significant differences in the number of throws between the control, caffeine or
      placebo groups. However, plasma lactate was systemically higher and perceived
      exertion lower in the subjects who ingested caffeine compared to either the
      control or placebo subjects (p < 0.05). In conclusion, caffeine did not improve
      performance during the judo fitness test after a 5-day weight loss period, but
      reduced perceived exertion and increased plasma lactate. 

PMID- 25054555
TI  - Parental evaluation of processes of care in relation to the child, parent and
      family characteristics.
AB  - The Measure of Processes of Care (MPOC) is a questionnaire for parents used to
      evaluate the behaviours of healthcare providers. We applied its 20-item version
      (MPOC-20) to explore the associations between parental evaluation of processes of
      care and child, parent and family characteristics in Slovenia. A novelty of our
      approach was the emphasis on the role of a key person. Parents of 235 children
      who were admitted as inpatients or outpatients of six institutions (hospitals and
      health centres) because of chronic illness or disability participated in the
      study. Parents were asked to fill in a general questionnaire on several
      characteristics of the child, child's health problems, the family and the therapy
      programmes, and MPOC-20. Univariate associations of the five MPOC-20 scale scores
      with child, parent and family characteristics were tested first. Multiple linear
      regression was used for modelling scale scores in relation to child, parent and
      family characteristics. The analyses singled out availability of a key person as
      the factor most consistently and unequivocally influencing parental satisfaction.
      We also found a general positive effect of male sex of the child on the MPOC-20
      scores. Neither the present age of children nor age at the onset of health
      problems was found to be associated with MPOC-20 scores. We found no notable
      association of the number of health problems with the MPOC-20 scores, but
      observed clear differences when comparing parental satisfaction with processes of
      care between different participating institutions. 

PMID- 25054559
TI  - Jet-cooled laser-induced fluorescence spectroscopy of cyclohexoxy: rotational and
      fine structure of molecules in nearly degenerate electronic States.
AB  - The rotational structure of the previously observed B(2)A' <- X(2)A" and B(2)A' <
      A(2)A' laser-induced fluorescence spectra of jet-cooled cyclohexoxy radical (c
      C6H11O) [ Zu, L.; Liu, J.; Tarczay, G.; Dupre, P; Miller, T. A. Jet-cooled laser
      spectroscopy of the cyclohexoxy radical. J. Chem. Phys. 2004 , 120 , 10579 ] has
      been analyzed and simulated using a spectroscopic model that includes the
      coupling between the nearly degenerate X and A states separated by DeltaE. The
      rotational and fine structure of these two states is reproduced by a 2-fold model
      using one set of molecular constants including rotational constants, spin
      rotation constants (epsilon's), the Coriolis constant (Azetat), the quenched spin
      orbit constant (azetaed), and the vibronic energy separation between the two
      states (DeltaE0). The energy level structure of both states can also be
      reproduced using an isolated-state asymmetric top model with rotational constants
      and effective spin-rotation constants (epsilon's) and without involving Coriolis
      and spin-orbit constants. However, the spin-orbit interaction introduces
      transitions that have no intensity using the isolated-state model but appear in
      the observed spectra. The line intensities are well simulated using the 2-fold
      model with an out-of-plane (b-) transition dipole moment for the B <- X
      transitions and in-plane (a and c) transition dipole moment for the B <- A
      transitions, requiring the symmetry for the X (A) state to be A" (A'), which is
      consistent with a previous determination and opposite to that of isopropoxy, the
      smallest secondary alkoxy radical. The experimentally determined A-X separation
      and the energy level ordering of these two states with different (A' and A")
      symmetries are consistent with quantum chemical calculations. The 2-fold model
      also enables the independent determination of the two contributions to the A-X
      separation: the relativistic spin-orbit interaction (magnetic effect) and the
      nonrelativistic vibronic separation between the lowest vibrational energy levels
      of these two states due to both electrostatic interaction (Coulombic effect) and
      difference in zero-point energies (kinetic effect). 

PMID- 25054561
TI  - Illuminating surface atoms in nanoclusters by differential X-ray absorption
      spectroscopy.
AB  - We use differential extended X-ray absorption fine structure (Delta-EXAFS) to
      monitor the Ar-induced surface restructuring of silica-supported Pd nanoclusters
      (1 nm diameter) at 77 K. Delta-EXAFS analysis shows 9 +/- 2 nearest-neighbor Pd
      Pd bonds expand by 0.104 +/- 0.005 A as a result of Ar adsorption. Atomistic
      molecular dynamics simulations provide evidence for a model in which Ar drives
      restructuring of under-coordinated Pd atoms, leading to an increased Pd-Pd bond
      length of surface Pd atoms with no change in overall nearest-neighbor Pd-Pd
      coordination number. Based on observations from the atomistic simulations, it is
      likely that under-coordinated atoms are trapped in metastable states at 77 K and
      Ar provides the kinetic energy needed to overcome the barrier for surface
      restructuring. Together, experiment and theory highlight the ability of Delta
      EXAFS to probe surface atoms of Pd nanoclusters. 

PMID- 25054560
TI  - PGE2 promotes apoptosis induced by cytokine deprivation through EP3 receptor and
      induces Bim in mouse mast cells.
AB  - Increased mast cell numbers are observed at sites of allergic inflammation and
      restoration of normal mast cell numbers is critical to the resolution of these
      responses. Early studies showed that cytokines protect mast cells from apoptosis,
      suggesting a simple model in which diminished cytokine levels during resolution
      leads to cell death. The report that prostaglandins can contribute both to
      recruitment and to the resolution of inflammation together with the demonstration
      that mast cells express all four PGE2 receptors raises the question of whether a
      single PGE2 receptor mediates the ability of PGE2 to regulate mast cell survival
      and apoptosis. We report here that PGE2 through the EP3 receptor promotes cell
      death of mast cells initiated by cytokine withdrawal. Furthermore, the ability of
      PGE2 to limit reconstitution of tissues with cultured mast cells is lost in cell
      lacking the EP3 receptor. Apoptosis is accompanied by higher dissipation of
      mitochondrial potential (DeltaPsim), increased caspase-3 activation, chromatin
      condensation, and low molecular weight DNA cleavage. PGE2 augmented cell death is
      dependent on an increase in intracellular calcium release, calmodulin dependent
      kinase II and MAPK activation. Synergy between the EP3 pathway and the intrinsic
      mitochondrial apoptotic pathway results in increased Bim expression and higher
      sensitivity of mast cells to cytokine deprivation. This supports a model in which
      PGE2 can contribute to the resolution of inflammation in part by augmenting the
      removal of inflammatory cells in this case, mast cells. 

PMID- 25054563
TI  - Myocardial effects of IMVAMUNE.

PMID- 25054564
TI  - Smallpox vaccines and eczema.

PMID- 25054562
TI  - Huntingtin is critical both pre- and postsynaptically for long-term learning
      related synaptic plasticity in Aplysia.
AB  - Patients with Huntington's disease exhibit memory and cognitive deficits many
      years before manifesting motor disturbances. Similarly, several studies have
      shown that deficits in long-term synaptic plasticity, a cellular basis of memory
      formation and storage, occur well before motor disturbances in the hippocampus of
      the transgenic mouse models of Huntington's disease. The autosomal dominant
      inheritance pattern of Huntington's disease suggests the importance of the mutant
      protein, huntingtin, in pathogenesis of Huntington's disease, but wild type
      huntingtin also has been shown to be important for neuronal functions such as
      axonal transport. Yet, the role of wild type huntingtin in long-term synaptic
      plasticity has not been investigated in detail. We identified a huntingtin
      homolog in the marine snail Aplysia, and find that similar to the expression
      pattern in mammalian brain, huntingtin is widely expressed in neurons and glial
      cells. Importantly the expression of mRNAs of huntingtin is upregulated by
      repeated applications of serotonin, a modulatory transmitter released during
      learning in Aplysia. Furthermore, we find that huntingtin expression levels are
      critical, not only in presynaptic sensory neurons, but also in the postsynaptic
      motor neurons for serotonin-induced long-term facilitation at the sensory-to
      motor neuron synapse of the Aplysia gill-withdrawal reflex. These results suggest
      a key role for huntingtin in long-term memory storage. 

PMID- 25054567
TI  - Robotic surgery for colorectal cancer: systematic review of the literature.
AB  - INTRODUCTION: Surgical practice has been changed since the introduction of
      robotic techniques and robotic colorectal surgery is an emerging field.
      Innovative robotic technologies have helped surgeons overcome many technical
      difficulties of conventional laparoscopic surgery. Herein, we review the clinical
      studies regarding the application of surgical robots in resections for colorectal
      cancer. METHODS: A systematic review of the literature was conducted for articles
      published up to September 9, 2012, using the MEDLINE database. The keywords that
      were used in various combinations were: "surgical robotics," "robotic surgery,"
      "computer-assisted surgery," "colectomy," "sigmoid resection," "sigmoidectomy,"
      and "rectal resection." RESULTS: Fifty-nine articles reporting on robot-assisted
      resections of colon and/or rectum were identified and 41 studies were finally
      included in the analysis. A total of 1635 colorectal procedures were performed:
      254 right colectomies, 185 left colectomies/sigmoid resections, 969 anterior
      resections, 182 abdominoperineal or intersphincteric resections, 34 colectomies
      (without being specified as right or left), and 11 total/subtotal colectomies. In
      general, blood loss, conversion rates, and complications were low but the
      operative time was longer than the open procedures, whereas the duration of
      hospitalization was shorter. The number of harvested lymph nodes was also quite
      satisfactory. CONCLUSIONS: Robotic colorectal operations provide favorable
      results, with acceptable operative times and low conversion rates and morbidity.
      Surgical robots may provide additional benefits treating challenging pathologies,
      such as rectal cancer. Further clinical studies and long-term follow-up are
      required to better evaluate the outcomes of robotic colorectal surgery.

PMID- 25054566
TI  - Is previous respiratory disease a risk factor for lung cancer?
AB  - RATIONALE: Previous respiratory diseases have been associated with increased risk
      of lung cancer. Respiratory conditions often co-occur and few studies have
      investigated multiple conditions simultaneously. OBJECTIVES: Investigate lung
      cancer risk associated with chronic bronchitis, emphysema, tuberculosis,
      pneumonia, and asthma. METHODS: The SYNERGY project pooled information on
      previous respiratory diseases from 12,739 case subjects and 14,945 control
      subjects from 7 case-control studies conducted in Europe and Canada. Multivariate
      logistic regression models were used to investigate the relationship between
      individual diseases adjusting for co-occurring conditions, and patterns of
      respiratory disease diagnoses and lung cancer. Analyses were stratified by sex,
      and adjusted for age, center, ever-employed in a high-risk occupation, education,
      smoking status, cigarette pack-years, and time since quitting smoking.
      MEASUREMENTS AND MAIN RESULTS: Chronic bronchitis and emphysema were positively
      associated with lung cancer, after accounting for other respiratory diseases and
      smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20
      1.48 and OR, 1.50; 95% CI, 1.21-1.87, respectively). A positive relationship was
      observed between lung cancer and pneumonia diagnosed 2 years or less before lung
      cancer (OR, 3.31; 95% CI, 2.33-4.70 for men), but not longer. Co-occurrence of
      chronic bronchitis and emphysema and/or pneumonia had a stronger positive
      association with lung cancer than chronic bronchitis "only." Asthma had an
      inverse association with lung cancer, the association being stronger with an
      asthma diagnosis 5 years or more before lung cancer compared with shorter.
      CONCLUSIONS: Findings from this large international case-control consortium
      indicate that after accounting for co-occurring respiratory diseases, chronic
      bronchitis and emphysema continue to have a positive association with lung
      cancer.

PMID- 25054568
TI  - Laparoscopic Roux-en-Y gastric bypass for type 2 diabetes mellitus in nonobese
      Chinese patients.
AB  - BACKGROUND: Although bariatric surgery performed for morbid obesity has been
      shown to significantly improve type 2 diabetes mellitus (T2DM), data on its
      effectiveness to improve T2DM in nonobese patients are scarce. The present pilot
      study evaluated the clinical effects of laparoscopic Roux-en-Y gastric bypass
      surgery (LRYGB) in Chinese T2DM patients with body mass index (BMI) <=27.5 kg/m.
      MATERIALS AND METHODS: A total of 68 consecutive patients with uncontrolled T2DM
      underwent LRYGB from May 2010 to March 2012. All patients were subjected to
      follow-up controls with anthropometric and metabolic indices at 1, 3, 6, and 12
      months after surgery. Glycemic control was evaluated. RESULTS: One year after the
      surgery, LRYGB resulted in 69.4%+/-52.2% excess weight loss percentage (%EWL),
      remission of T2DM in 80.9% of all the patients. In the group of T2DM patients
      with BMI<=27.5 kg/m (n=28), 9 (32.1%) cases showed T2DM remission, 10 (35.7%)
      showed glycemic control, 7 (25%) showed improvement, and 2 (7.1%) were unchanged.
      The change in BMI, waist circumference, and the plasma levels of FPG, HbA1C,
      triglycerides, HDL-C, and insulin were statistically significance at 1 year (P<0.
      05). There was no perioperative mortality, but 6 (8.8%) patients experienced
      complications. CONCLUSIONS: LRYGB resulted in significant weight loss and
      remission of T2DM in Chinese patients. Despite a lower response rate of surgery
      treatment compared with obese patients, T2DM patients with BMI<=27.5 kg/m still
      exhibited improvement and remission of T2DM. Diabetic patients should consider
      bariatric surgery, especially if traditional pharmacotherapy has not been
      effective. Longer follow-up is required for better evaluation.

PMID- 25054569
TI  - Laparoscopic versus open gastric wedge resection for primary gastrointestinal
      tumors: clinical outcomes and health care costs analysis.
AB  - The study aimed to compare laparoscopic wedge resection (LWR) versus open-wedge
      resections (OWR) for primary gastrointestinal stromal tumors (GISTs) of the
      stomach. Twenty-five patients who underwent LWR were matched by tumor size and
      location with 25 patients who underwent OWR. GISTs close to the pylorus or the
      esophagogastric junction, incidental, and metastatic GISTs were excluded.
      Demographic, clinical, and histologic variables did not differ between groups.
      Estimated blood loss, time to flatus, and duration of hospitalization were
      significantly lower in the LWR group. Overall, 6 patients developed minor
      postoperative complications that were medically treated. Mortality was nil. No
      group difference was observed for the incidence of diseases during the follow-up
      (average, 46.8 mo). The OWR procedure had significantly higher costs (+34%) than
      the LWR. Both techniques appear safe and oncologically feasible. However,
      laparoscopy is associated with faster recovery and shorter hospital stay, which
      reflect advantages in terms of contracted costs for the health care system.

PMID- 25054571
TI  - Electromyography Activation Levels of the 3 Gluteus Medius Subdivisions During
      Manual Strength Testing.
AB  - STUDY DESIGN: Cross-sectional. CONTEXT: Gluteus medius (GM) muscle dysfunction is
      associated with overuse injury. The GM is functionally composed of 3 separate
      subdivisions: anterior, middle, and posterior. Clinical assessment of the GM
      subdivisions is relevant to detect strength and activation deficits and guide
      specific rehabilitation programs. However, the optimal positions for assessing
      the strength and activation of these subdivisions are unknown. OBJECTIVE: The
      first aim was to establish which strength-testing positions produce the highest
      surface electromyography (sEMG) activation levels of the individual GM
      subdivisions. The second aim was to evaluate differences in sEMG activation
      levels between the tested and contralateral (stabilizing) leg. METHOD: Twenty
      healthy physically active male subjects participated in this study. Muscle
      activity using sEMG was recorded for the GM subdivisions in 8 different strength
      testing positions and analyzed using repeated-measures analysis of variance.
      RESULTS: Significant differences between testing positions for all 3 GM
      subdivisions were found. There were significant differences between the tested
      and the contralateral anterior and middle GM subdivisions (P < .01). The
      posterior GM subdivision showed no significant difference (P = .154). CONCLUSION:
      Side-lying in neutral and side-lying with hip internal rotation are the 2
      positions recommended to evaluate GM function and guide specific GM
      rehabilitation.

PMID- 25054572
TI  - Sex-related differences in explosive actions during late childhood.
AB  - The purpose of this study was to examine sex-related differences in explosive
      actions during late childhood, while accounting for body size and maturity, and
      determine the predictive model responsible for performance. Sixty-eight boys
      (11.0 +/- 1.1 years) and 45 girls (11.3 +/- 0.9 years) performed a vertical and
      horizontal jump, 30-m sprint, and change of direction (COD) time trial. After
      allometric analysis, a common sex scaling factor of body mass was used for
      vertical (b = 1.02) and horizontal (b = 0.97) power. No significant sex
      difference in relative leg power was found before and after controlling for
      maturity status. Gender differences in 10 m, the Zigzag section, and flying 10 m
      of the COD task were found significant once adjusted for maturity (p <= 0.05).
      However, boys performed better than girls in 20- and 30-m sprint and the COD time
      trial regardless of maturity status (p <= 0.05). Reduced endomorphy in boys was
      the best predictor of explosive actions (R = 7-22%), whereas female performance
      was best explained by mass and maturity status (R = 15-19%). Jump power-specific
      allometric scaling factors need to be determined to account for body size. A
      training emphasis on sprinting and COD at a younger age in girls compared with
      boys is recommended because of their earlier onset of puberty and reduced natural
      ability in these tasks. Somatotype, age, maturity, and body mass should be
      monitored during the development of youth athletes to better understand explosive
      performance.

PMID- 25054573
TI  - Accelerometer and GPS-derived running loads and injury risk in elite Australian
      footballers.
AB  - The purpose of this study was to investigate the relationship between overall
      physical workload (global positioning systems [GPS]/accelerometer) measures and
      injury risk in elite Australian football players (n = 46) during a season.
      Workload data and (intrinsic) injury incidence were monitored across preseason
      and in-season (18 matches) phases. Multiple regression was used to compare
      cumulative (1-, 2-, 3-, and 4-weekly loads) and absolute change (from previous-to
      current week) in workloads between injured and uninjured players for all
      GPS/accelerometer-derived variables: total distance, V1 distance (total distance
      above individual's aerobic threshold speed), sprint distance, force load,
      velocity load, and relative velocity change. Odds ratios (ORs) were calculated to
      determine the relative injury risk. Cumulative loads showed the strongest
      relationship with greater intrinsic injury risk. During preseason, 3-weekly
      distance (OR = 5.489, p = 0.008) and 3-weekly sprint distance (OR = 3.667, p =
      0.074) were most indicative of greater injury risk. During in-season, 3-weekly
      force load (OR = 2.530, p = 0.031) and 4-weekly relative velocity change (OR =
      2.244, p = 0.035) were associated with greater injury risk. No differences in
      injury risk between years of Australian Football League system experience and
      GPS/accelerometer data were seen. From an injury risk (prevention) perspective,
      these findings support consideration of several GPS/accelerometer running load
      variables in Australian football players. In particular, cumulative weekly loads
      should be closely monitored, with 3-weekly loads most indicative of a greater
      injury risk across both seasonal phases.

PMID- 25054574
TI  - An integrated approach to identifying clinically relevant targets in pediatric
      gliomas.

PMID- 25054575
TI  - Future clinical potential of oncolytic virotherapy for pediatric CNS tumors.

PMID- 25054578
TI  - Vaccine-based immunotherapy for glioblastoma.
AB  - Glioblastoma remains the most lethal human brain tumor, despite the advent of
      multimodal treatment approaches. Because immune tolerance plays an important role
      in tumor progression, adding immunotherapy has become an attractive and
      innovative treatment approach for these aggressive tumors. Several early-phase
      clinical trials have demonstrated that vaccine-based immunotherapies, including
      dendritic cell therapy, peptide-based vaccines and vaccines containing autologous
      tumor lysates, are feasible and well tolerated. These trials have revealed
      promising trends in overall survival and progression-free survival for patients
      with glioblastoma, and have paved the way for ongoing randomized controlled
      trials.

PMID- 25054579
TI  - Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical
      investigation and patient management.
AB  - Oligodendrogliomas are heterogeneous tumors with a variable response to
      treatment. This clinical variability underlines the urgent need for markers that
      can reliably aid diagnosis and guide clinical decision-making. Long-term follow
      up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed
      anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a
      predictive marker of response to procarbazine, lomustine and vincristine
      chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter
      hypermethylation has been strongly associated with glioma CpG island
      hypermethylation phenotype (G-CIMP+) status, this has been suggested as an
      epiphenomenon of genome-wide methylation, conferring a more favorable prognosis.
      Molecular profiling of these tumors has identified several other markers with
      potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require
      further validation before they can be implemented as clinical decision-making
      tools. Additionally, recent data on the clinical significance of intrinsic glioma
      subtyping appears promising. Indeed, existing evidence suggests that
      comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are
      superior to single molecular markers. Clearly, with evolving treatment strategies
      and in the era of individualized therapy, broader omics-based molecular
      evaluations are required to improve outcome prediction and to identify patients
      who will benefit from specific treatment strategies.

PMID- 25054583
TI  - Strongly coupled Pd nanotetrahedron/tungsten oxide nanosheet hybrids with
      enhanced catalytic activity and stability as oxygen reduction electrocatalysts.
AB  - The design and synthesis of highly active oxygen reduction reaction (ORR)
      catalysts with strong durability at low cost is extremely desirable but still
      remains a significant challenge. Here we develop an efficient strategy that
      utilizes organopalladium(I) complexes containing palladium-palladium bonds as
      precursors for the synthesis of strongly coupled Pd tetrahedron-tungsten oxide
      nanosheet hybrids (Pd/W18O49) to improve the electrocatalytic activity and
      stability of Pd nanocrystals. The hybrid materials are synthesized by direct
      nucleation, growth, and anchoring of Pd tetrahedral nanocrystals on the in situ
      synthesized W18O49 nanosheets. Compared to supportless Pd nanocrystals and
      W18O49, their hybrids exhibited not only surprisingly high activity but also
      superior stability to Pt for the ORR in alkaline solutions. X-ray photoelectron
      spectroscopy, high-resolution transmission electron microscopy, and
      electrochemical analyses indicated that the enhanced electrocatalytic activity
      and durability are associated with the increased number and improved catalytic
      activity of active sites, which is induced by the strong interaction between the
      Pd tetrahedrons and W18O49 nanosheet supports. The present study provides a novel
      strategy for synthesizing hybrid catalysts with strong chemical attachment and
      electrical coupling between nanocatalysts and supports. The strategy is expected
      to open up exciting opportunities for developing a novel class of metal-support
      hybrid nanoelectrocatalysts with improved ORR activity and durability for both
      fuel cells and metal-air batteries. 

PMID- 25054580
TI  - Targeting of histone deacetylases in brain tumors.
AB  - Histone deacetylase inhibitors (HDACis) have fascinated researchers in almost all
      fields of oncology for many years owing to their pleiotropic effects on nearly
      every aspect of cancer biology. Since the approval of the first HDACi vorinostat
      for the treatment of cutaneous T-cell leukemia in 2006, more than a hundred
      clinical trials have been initiated with a HDACi as a single agent or in
      combination therapy. Although a number of epigenetic and nonepigenetic molecular
      mechanisms of action have been proposed, biomarkers for response prediction and
      patient selection are still lacking. One of the inherent problems in the field of
      HDACis is their 'reverse' history of drug development: these compounds reached
      clinical application at an early stage, before the biology of their targets,
      HDAC1-11, was sufficiently understood. This review summarizes the current
      knowledge on the human family of HDACs as drug targets in pediatric and adult
      brain tumors, the efficacy and molecular action of HDACis in preclinical models,
      as well as the current status of the clinical development of these compounds in
      the field of neuro-oncology.

PMID- 25054581
TI  - Medulloblastoma: recurrence and metastasis.
AB  - Medulloblastoma is the most common malignant brain tumor of childhood. Although
      there is now long-term survival or cure for the majority of children, the
      survivors bear a significant burden of complications due, at least in part, to
      the intense therapies given to ensure eradication of the tumor. Significant
      efforts have been made over the years to be able to distinguish between patients
      who do and do not need intensive therapies. This review summarizes the history
      and current state of clinical risk stratification, pathologic diagnosis and
      genetics. Recent developments in correlation between genetics and pathology,
      genome-wide association studies and the biology of medulloblastoma metastasis are
      discussed in detail. The current state of clinical treatment trials are reviewed
      and placed into the perspective of potential novel therapies in the near term.

PMID- 25054584
TI  - Gastric sonography in the severely obese surgical patient: a feasibility study.
AB  - BACKGROUND: Gastric ultrasonography allows qualitative and quantitative
      assessment of gastric contents and volume in nonobese subjects. In this study, we
      sought to determine the feasibility of gastric ultrasound in severely obese
      patients (body mass index [BMI] >=35 kg/m). We defined feasibility as the ability
      to identify a full cross section of the gastric antrum in at least 80% of
      subjects when imaged in the right lateral decubitus position. METHODS: This was a
      prospective cohort study on fasted surgical patients with BMI >35 kg/m. The
      primary outcome measure was the feasibility of gastric sonography. Secondary
      outcomes included the distribution of antral grade following an existing 3-point
      grading system. In addition, the antral cross-sectional area (CSA) and gastric
      volumes in this cohort were compared with historical data from a published study
      in nonobese individuals. Time to image capture, antral wall thickness, and depth
      of the antrum are also reported. RESULTS: Sixty patients (BMI range 35.1-68.7)
      were studied. The antrum was identified in 95% of subjects in the right lateral
      decubitus (95% CI, 0.86-0.99) and 90% of subjects in the supine position.
      Definition of antral grade (0-2) was possible in 88.3% (95% CI, 0.77-0.95) of
      cases. As expected, antral grade correlated with antral CSA and gastric volumes
      (P < 0.0001). When compared with historical data, our results suggest that
      severely obese patients have a larger baseline CSA and gastric volume than
      nonobese patients (P < 0.001) but a similar gastric volume per unit of weight (P
      = 0.141). CONCLUSIONS: Gastric ultrasound assessment is feasible in fasted
      severely obese subjects. Our data also suggest that obese individuals present
      larger antral size and gastric volume than their nonobese counterparts.

PMID- 25054585
TI  - In situ ATR and DRIFTS studies of the nature of adsorbed CO2 on
      tetraethylenepentamine films.
AB  - CO2 adsorption/desorption onto/from tetraethylenepentamine (TEPA) films of 4, 10,
      and 20 MUm thicknesses were studied by in situ attenuated total reflectance (ATR)
      and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS)
      techniques under transient conditions. Molar absorption coefficients for adsorbed
      CO2 were used to determine the CO2 capture capacities and amine efficiencies
      (CO2/N) of the films in the DRIFTS system. Adsorption of CO2 onto surface and
      bulk NH2 groups of the 4 MUm film produced weakly adsorbed CO2, which can be
      desorbed at 50  degrees C by reducing the CO2 partial pressure. These weakly
      adsorbed CO2 exhibit low ammonium ion intensities and could be in the form of
      ammonium-carbamate ion pairs and zwitterions. Increasing the film thickness
      enhanced the surface amine-amine interactions, resulting in strongly adsorbed ion
      pairs and zwitterions associated with NH and NH2 groups of neighboring amines.
      These adsorbed species may form an interconnected surface network, which slowed
      CO2 gas diffusion into and diminished access of the bulk amine groups (or amine
      efficiency) of the 20 MUm film by a minimum of 65%. Desorption of strongly
      adsorbed CO2 comprising the surface network could occur via dissociation of
      NH3(+)/NH2(+)...NH2/NH ionic hydrogen bonds beginning from 60 to 80  degrees C,
      followed by decomposition of NHCOO(-)/NCOO(-) at 100  degrees C. These results
      suggest that faster CO2 diffusion and adsorption/desorption kinetics could be
      achieved by thinner layers of liquid or immobilized amines.

PMID- 25054586
TI  - Airways resistance in bronchial challenge testing.
AB  - INTRODUCTION: Measurement of airways resistance is an alternative to spirometry
      to assess airflow obstruction. This can be measured by the interrupter technique
      (RInt) using a handheld device. We wished to know how RInt compared to forced
      expiratory volume in 1 s (FEV1) during a histamine challenge test. METHODS:
      Twenty-nine (13 male) patients, aged 48.9 (SD 15.3) years, referred for a
      histamine challenge test, were enrolled. Patients had measurement of RInt then
      FEV1 after administration of saline and following doubling concentrations of
      histamine from 0.06 to 8 mg/ml. Extrapolation of the log dose-response curve was
      undertaken to calculate the concentration (provocation concentration, PC) causing
      an increase airways resistance of 20, 40, 60, 80, 100, 120, 140 and 160% (RInt
      PC1.2 to RInt PC2.6) and a reduction in FEV1 by 20% (FEV1 PC20). The number of
      patients with a negative challenge (i.e. PC>8 mg/ml histamine) was calculated for
      FEV1 and each change in airway resistance. Patients assessed their procedure
      provoked symptoms of breathlessness, dizziness and tiredness on a visual analogue
      scale. RESULTS: Geometric (SD) PC20 for FEV1 was 1.87 (0.5) mg/ml with 11
      patients having a negative challenge. A RInt PC20 had the best agreement with
      FEV1 PC20 [Kappa 0.39 (p=0.024)]. There is a significant negative correlation
      between RInt and FEV1 (r=-0.94). The respective mean (SD) breathlessness,
      dizziness and tiredness scores for RInt were 26 (4) mm, 18 (3) mm, 22 (4) mm and
      for spirometry were 40 (4) mm, 27 (5) mm, 31 (5) mm. There was a significant
      (p<0.05) difference for breathlessness. CONCLUSION: RInt was tolerated better
      than spirometry. A doubling of airways resistance had the best agreement with
      PC20 FEV1.

PMID- 25054587
TI  - Urban adults' perceptions of factors influencing asthma control.
AB  - OBJECTIVE: To identify urban adults' perceptions of facilitators and barriers to
      asthma control, including the role of self-care, medications, environmental
      trigger remediation, and primary care. METHODS: Semi-structured open-ended
      qualitative interviews were conducted. Audio recordings were transcribed verbatim
      and entered into NVivo 10.0 (QSR International Pty Ltd, Doncaster, Victoria,
      Australia) for coding, analysis, and integration with demographic and asthma
      control data. RESULTS were analyzed by the level of asthma control. A modified
      grounded theory approach was used in the analysis. RESULTS: Thirty-five adults
      with persistent asthma (94% Black; 71% female; 71% with uncontrolled asthma) from
      the five West Philadelphia zip codes with the highest asthma burden participated.
      Generally, all participants understood the roles of inhaled corticosteroid (ICS)
      and short-acting beta-2 agonist (SABA) therapies in asthma self-care although
      they attributed systemic side effects to topical ICS administration. Compared
      with participants with controlled asthma, uncontrolled participants reported
      overusing SABAs, underusing ICS, rejecting medical and trigger remediation
      advice, having more negative experiences with primary care providers, and
      preferring more unconventional strategies to prevent or manage asthma symptoms.
      CONCLUSIONS: Personal health beliefs about control can undermine adherence to
      medical and environmental remediation advice and likely contributes to high rates
      of uncontrolled asthma in this population. Clinicians need to know whether, and
      to what degree, these health beliefs can be modified. It is likely that new
      models of care, such as patient-centered shared decision-making approaches, and
      new partners, such as community health workers, may be required to modify these
      beliefs. This would be an important first step to enhance asthma control in
      vulnerable populations.

PMID- 25054588
TI  - Ultrasensitive electrochemical detection of microRNA based on an arched probe
      mediated isothermal exponential amplification.
AB  - In this work, a simple and label-free electrochemical biosensor is developed for
      microRNA (miRNA) detection on the basis of an arched probe mediated isothermal
      exponential amplification reaction (EXPAR). The arched probe assembled on the
      electrode surface consists of two strands that are partially complementary to
      each other at both ends. The target can hybridize with the complementary sequence
      of the arched structure, leading to the cleavage of the probe. The strand fixed
      on the surface of the electrode self-assembles, in the presence of hemin, to G
      quadruplex unit, yielding electrochemical signals. The other strand liberated
      into the solution triggers the EXPAR to recycle and regenerate targets. This
      method exhibits ultrahigh sensitivity toward miRNA with detection limits of 5.36
      fM and a detection range of 3 orders of magnitude. The biosensor is capable of
      discriminating a single-nucleotide difference between concomitant miRNA and
      performs well in analyzing crude extractions from cancer cell lines. 

PMID- 25054589
TI  - Improving survival from intentional mass casualty incidents: the need for a
      national curriculum.

PMID- 25054591
TI  - ScienceDirect: the indexation which RBR lacked.

PMID- 25054590
TI  - Sensory neurons do not induce motor neuron loss in a human stem cell model of
      spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to
      paralysis and early death due to reduced SMN protein. It is unclear why there is
      such a profound motor neuron loss, but recent evidence from fly and mouse studies
      indicate that cells comprising the whole sensory-motor circuit may contribute to
      motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells
      derived from SMA patients to test whether sensory neurons directly contribute to
      motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem
      cells and found no difference in neuron generation or survival, although there
      was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA
      induced pluripotent stem cell derived sensory neurons with control induced
      pluripotent stem cell derived motor neurons, we found no significant reduction in
      motor neuron number or glutamate transporter boutons on motor neuron cell bodies
      or neurites. We conclude that SMA sensory neurons do not overtly contribute to
      motor neuron loss in this human stem cell system. 

PMID- 25054592
TI  - Inequality in the distribution of rheumatologists in Brazil: correlation with
      local of medical residency, Gross Domestic Product and Human Development Index.
AB  - OBJECTIVE: To assess the distribution of rheumatologists in Brazil and their
      correlation with Medical Residency specialization offer, Gross Domestic Product
      (Gdp) And Municipal Human Development Index (HDI-M) of units of the federation
      (UFs). METHODS: Query to various official databases, data summarization by
      techniques for descriptive statistics and cross-referenced information. For
      correlation analysis, we used the Spearman correlation coefficient (r). RESULTS:
      There were 1229 rheumatologists regularly registered in the country. The Northern
      region had only 3.6% of the total (n = 44), while the Southeast had 42.2% (n =
      519). The State capitals, added to the five largest municipalities in each UF,
      concentrated 75.8% of these specialists (n = 931). In total, 49.9% of
      rheumatologists offered treatment at SUS. A general ratio of 157,809 inhabitants
      per rheumatologist in Brazil was determined, but with wide variation among UFs
      with respect to this ratio. In the years 2000-2012, there were 593 Rheumatology
      Residency graduated physicians in Brazil. We observed a positive correlation
      among number of rheumatologists compared with GDP (r = 0.94), HDI-M of the State
      capitals (r = 0.77) and number of Rheumatology Residency graduated physicians (r
      = 0.79) in UFs. CONCLUSIONS: We noted a strong concentration of rheumatologists
      in State capitals and larger municipalities, with noticeable inequalities also
      between UFs and country regions. The distribution of these professionals
      accompanied GDP, HDI-M of the State capital and number of Rheumatology Residency
      graduated physicians, suggesting that factors related to income opportunities and
      human development and the place of speciality training may influence the
      geographical fixation of rheumatologists.

PMID- 25054593
TI  - Otorhinolaryngological findings in a group of patients with rheumatic diseases.
AB  - INTRODUCTION: Otorhinolaryngological manifestations of rheumatologic diseases
      represent a great challenge not only to the generalistphysician but also to the
      ENT doctor andrheumatologist. They often represent early manifestations of an
      autoimmune disorder which requires prompt and aggressive immunosuppressive
      treatment. Auditory, nasal, laryngeal and eye symptoms can be the first
      manifestation of rheumatic diseases and their proper assessment helps the doctor
      to identify signs of disease activity. The objective of this study is to identify
      the ENT manifestations in patients with rheumatic diseases in a high complexity
      hospital, regarding facilitating an early diagnosis and treatment. METHODS: We
      performed clinical and complete otorhinolaryngological evaluations in patients
      selected from the outpatient rheumatology in a standardized manner by the use of
      a standardized form filling during the secondhalf of 2010. RESULTS: In the study
      group, systemic lupus erythematosus (SLE) patients had predominantly laryngeal
      manifestations, while patients with Sjogren's syndrome showed a higher prevalence
      of otologic manifestations. Changes in audiometric tests were found in 53% of
      Wegener's granulomatosis (WG) patients, 80% of relapsing polychondritis (RP), 33%
      of systemic lupus erythematosus (SLE) and 50% of Churg-Strauss syndrome (SCS).
      Regarding nasal alterations, these were found so prevalent in all conditions,
      especially Churg-Strauss syndrome. DISCUSSION AND CONCLUSION: This study
      demonstrated that most patients treated in our hospital has the ENT signs and
      symptoms commonly associated in previous studies on rheumatic diseases, but
      further studies with a larger number of patients must be made to establish such
      relations.

PMID- 25054594
TI  - Randomized controlled trial of a therapeutic intervention group in patients with
      fibromyalgia syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of a weekly interdisciplinary program (WIP)
      consisted of educational activities, physical therapy, stretching, ergonomics,
      posture guidance combined with cognitive behavioral strategies and approaches to
      psychosocial and occupational factors in order to determine whether this
      intervention would be effective to short and medium-term improvement of symptoms
      in these patients. METHODS: This was a single-center study, randomized single
      blind controlled trial with a sample test group (T), with a diagnosis of FMS (n =
      12), and a control group (C) subjected to Pain Clinic referral (n = 15). The
      instruments used at two different times were the Fibromyalgia Impact
      Questionnaire (FIQ), Visual Analogue Scale (VAS) and Post-Sleep Protocol (PSI).
      To assess quality of life, we used the SF-12. RESULTS: In samples, both groups
      were predominantly female, mean age of 42.5 +/- 9.8 years, 43% married, average
      schooling of 8.3 +/- 4.5 years. It was reported a mean of 4.2 years pain and an
      average of two years for the diagnosis of SFM from the group T. There was
      statistical difference between the groups in terms of efficacy post intervention
      WIP, in almost all outcome measures. CONCLUSION: It was found that weekly
      interdisciplinary program (WIP) has contributed to improving the quality of life
      of patients with fibromyalgia.

PMID- 25054595
TI  - Construction of a manual of work processes and techniques from Centro de
      Dispensacao de Medicamentos de Alto Custo (CEDMAC), Hospital de Clinicas,
      Unicamp.
AB  - The Centers for High Cost Medication (Centros de Medicacao de Alto Custo,
      CEDMAC), Health Department, Sao Paulo were instituted by project in partnership
      with the Clinical Hospital of the Faculty of Medicine, USP, sponsored by the
      Foundation for Research Support of the State of Sao Paulo (Fundacao de Amparo a
      Pesquisa do Estado de Sao Paulo, FAPESP) aimed at the formation of a statewide
      network for comprehensive care of patients referred for use of immunobiological
      agents in rheumatological diseases. The CEDMAC of Hospital de Clinicas,
      Universidade Estadual de Campinas (HC-Unicamp), implemented by the Division of
      Rheumatology, Faculty of Medical Sciences, identified the need for
      standardization of the multidisciplinary team conducts, in face of the
      specificity of care conducts, verifying the importance of describing, in manual
      format, their operational and technical processes. The aim of this study is to
      present the methodology applied to the elaboration of the CEDMAC/HC-Unicamp
      Manual as an institutional tool, with the aim of offering the best assistance and
      administrative quality. In the methodology for preparing the manuals at HC
      Unicamp since 2008, the premise was to obtain a document that is participatory,
      multidisciplinary, focused on work processes integrated with institutional rules,
      with objective and didactic descriptions, in a standardized format and with
      electronic dissemination. The CEDMAC/HC-Unicamp Manual was elaborated in 10
      months, with involvement of the entire multidisciplinary team, with 19 chapters
      on work processes and techniques, in addition to those concerning the
      organizational structure and its annexes. Published in the electronic portal of
      HC Manuals in July 2012 as an e-Book (ISBN 978-85-63274-17-5), the manual has
      been a valuable instrument in guiding professionals in healthcare, teaching and
      research activities. 

PMID- 25054596
TI  - Evaluation of respiratory impairment in patients with systemic lupus
      erythematosus with the six-minute walk test.
AB  - OBJECTIVE: Evaluate SLE stable patients, without overt respiratory compromise, by
      means of 6MWT. CASUISTIC AND METHODS: Forty-five stable SLE patients were
      enrolled. The ATS/ERS protocol for 6MWT, was used and two parameters with cut-off
      points were chosen. RESULTS: Forty-two patients were women. The mean age was 39
      +/- 11.4 years; mean duration of disease, 121 +/- 93.1 months; mean value of MRC,
      2 +/- 0; mean FVC, 85.9 +/- 34.2%; mean FEV1, 67.5 +/- 21.6%; mean MIP, 82 +/-
      58.4%; mean MEP, 78 +/- 37.3%; mean heart rate at rest, 75 +/- 12.8 bpm; mean
      respiratory rate at rest, 19 +/- 5.3 bpm; mean 6MWD, 478 +/- 82 m; mean SpO2 at
      rest was 98 +/- 0.8%; mean fall in SpO2, 4 +/- 6 points. When the study
      population was divided according to the 400-m walk distance cut-off value, the
      heart rate immediately before the test was significant lower in those
      participants who walked less than 400 m (p = 0.0043), just like the value of Borg
      scale (p = 0.0036); according to the presence of saturation >= 4, heart rate at
      the end of the test was significantly higher in those participants who were
      showing desaturation (p = 0.0170); MEP (p = 0.0282) and 6MWD (p = 0.0291) were
      significantly lower, and MIP showed a tendency towards being smaller (p =
      0.0504). FVC < normal inferior limit was significantly associated with the group
      with desaturation (p = 0.0274). CONCLUSION: Compared to 6MWD, desaturation was
      better suited to find the patients with the most compromised indexes in
      respiratory function tests.

PMID- 25054597
TI  - Analysis of the association of fatigue with clinical and psychological variables
      in a series of 371 Brazilian patients with rheumatoid arthritis.
AB  - OBJECTIVES: Fatigue is a highly subjective and extremely common symptom in
      patients with rheumatoid arthritis although it is difficult to characterize and
      define. The aim of this study was to assess fatigue in a cohort of Brazilian
      patients, and to analyze the relationship between fatigue and disease-specific
      variables. METHODS: 371 Brazilian patients diagnosed with rheumatoid arthritis
      according to the 1987 American College of Rheumatology classification criteria
      were prospectively investigated. Demographic, clinical and laboratorial data were
      obtained from hospitals records. The number of painful joints, bone mass index,
      disease duration, quality of life, functional capacity, anxiety and depression
      were recorded. Fatigue was evaluated using the subscale of Fatigue Assessment of
      Chronic Illness Therapy (FACIT-FATIGUE scale). RESULTS: The median fatigue score
      was 42.0 (10.0), negatively correlated with functional capacity (-0.507; P <
      0.001), anxiety and depression (-0.542 and -0.545; P < 0.001 respectively), and
      predominantly with physical domain of Short Form 36-item quality of life
      questionnaire (SF-36P: 0.584; P < 0.001). The scores were not associated with the
      erythrocyte sedimentation rate (-0.118; P < 0.05), C-reactive protein (-0.089; P
      < 0.05), disease activity (-0.250; P < 0.001) or the number of painful joints (
      0.135; P < 0.01). Confidence interval of 95% was applied for all measures.
      CONCLUSIONS: In this series of Brazilian patients with rheumatoid arthritis, we
      suggest a new significance for fatigue complains as an independent parameter not
      related with number of painful joints, disease or inflammatory activity scores.
      Psychological and functional impairments appear to be more related to fatigue.
      Additional studies and inclusion of standard measures for monitoring fatigue
      complains are required.

PMID- 25054598
TI  - Evaluation of postural control and quality of life in elderly women with knee
      osteoarthritis.
AB  - OBJECTIVE: To assess the balance in dynamic tasks and in the quality of life in
      elderly women with and without knee osteoarthritis. METHODS: Elderly women were
      divided into Group 1 (n = 12), consisting of participants with bilateral knee
      osteoarthritis (Kellgreen-Lawrence grade 1 and 2), and Group 2 (n = 12),
      consisting of controls. A force plate (EMG System do Brazil) was used to assess
      postural sway in dynamic tasks, whereas the quality of life was assessed by using
      the WHOQOL-Bref questionnaire. RESULTS: Student's t-test showed no statistical
      difference during sitting down and standing up from the chair (p > 0.05).
      However, stair ascent revealed difference in displacement speed (p < 0.05),
      whereas stair descent showed differences in both displacement speed and amplitude
      (p < 0.05). In the questionnaire, Group 1 showed values lower than those in the
      control group regarding physical domain (p < 0.05). CONCLUSION: Elderly women
      with knee osteoarthritis seemed to have more difficulty on stair descent task and
      had perception of worst physical domain. These findings were observed in OA
      group, even in the early stages of the disease, which shows the importance of
      even earlier interventions.

PMID- 25054599
TI  - Pre-operative anesthetic assessment of patients with rheumatoid arthritis.
AB  - The management and surgical interventions of problems directly or indirectly
      arising from rheumatoid arthritis vary drastically. Anesthesiologists and
      rheumatologists should be aware of the peculiarities of the anesthetic
      preoperative assessment of these patients, including the assessment of possible
      disorders of the airways, in addition to the intra-operative management and
      analysis of relevant pharmacological parameters. It is critical that the
      anesthetist is familiar with the peculiarities of the disease and the specific
      characteristics of drugs used in its treatment: thus, he/she will be able to plan
      the best possible anesthetic technique for the surgery in question, offering
      safety and comfort to his/her patient. It is up to the rheumatologist to know the
      procedure to which the patient will be submitted to and be aware of the most
      appropriate anesthetic technique in each case. This will allow a better
      interaction between the rheumatologist and the anesthesiologist in the pre
      anesthetic evaluation, through the sharing of relevant information on the
      articular and systemic involvement by the disease that might interfere with
      preoperative and intraoperative management. Furthermore, the information on the
      pre-anesthetic assessment and the choice of anesthetic technique will enable the
      rheumatologist to clarify any doubts that his/her patient and family may have, as
      well as to guide them as to whether or not the medications in use should be
      maintained, and eventually about the need for a supplemental dose of
      corticosteroid. The objective of this review is to acquaint the rheumatologist
      with key concepts related to the anesthetic preoperative assessment of patients
      diagnosed with RA, mainly including general notions that dictate the choice of
      the anesthetic technique. 

PMID- 25054600
TI  - Rituximab for rheumatoid arthrits treatment: a systematic review.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease
      characterized by systemic joint inflammation that often leads to significant
      disability. Several effective anti-TNF agents have been used, but some patients
      have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody
      indicated in such cases. METHODS: We conducted a systematic review to access
      efficacy and safety of rituximab in patients with active RA which have or have
      not been treated with anti-TNF agents before, and to relate outcome with RF and
      anti-CCP serology. We searched major electronics databases, grey literature and
      searched for references manually. We used Review Manager(r)5.1 for meta-analysis.
      RESULTS: We included six RCTs comparing rituximab 1000 mg with placebo.
      Methotrexate was used by both groups. Treatment with rituximab was more effective
      in naive and in anti-TNF treatment failure patients - ACR20/50/70 and EULAR
      response. We observed lower changes in Total Genant-modified Sharp score, erosion
      score and joint narrowing scores in the rituximab group, and SF-36, FACIT-T and
      HAQ-DI scores were also better in this group. There were no differences between
      groups regarding safety outcomes, with exception of acute injection reactions,
      which were more common on rituximab group. More RF/anti-CCP seropositive patients
      achieved ACR20 than RF/anti-CP negative patients in rituximab group. CONCLUSION:
      Available data support the use of rituximab for the treatment of RA, as it is an
      effective and safe option for naive and anti-TNF treatment failure patients. RF
      and anti-CCP seam to influence treatment results, but this inference needs
      further research.

PMID- 25054601
TI  - IgA nephropathy and polymyositis: a rare association.
AB  - Polymyositis is a systemic and idiopathic inflammatory myopathy that, besides
      muscle manifestation, may occur with respiratory involvement, gastrointestinal
      tract and rarely renal involvement. In this latter, there are only two cases of
      IgA nephropathy, but both in dermatomyositis. On the other hand, we reported, for
      the first time, a case of IgA nephropathy in polymyositis. 

PMID- 25054602
TI  - Spondyloptosis in athlete.
AB  - The adolescent athletes are at greater risk of low back pain and structural spine
      injuries. Spondylolysis is responsible for the majority of back pain cases in
      young athletes, rarely occurring in adults. We report a case of a 13-year-old
      judo female athlete, who came to our service with 5 months of progressive low
      back pain during training which was initially attributed to mechanical causes,
      without any further investigation by imaging methods. At admission, the patient
      had lumbar deformity, antalgic posture and bilaterally positive unipodalic lumbar
      hyperextension maneuver. After a research which showed spondyloptosis, the
      patient underwent surgery. In this article, we discuss, based on this case
      report, the diagnostic approach to low back pain in young athletes, since the
      complaint of chronic back pain can be a marker of a structural lesion that may be
      permanent and bring irreversible functional loss. 

PMID- 25054603
TI  - First report of mild Brazilian spotted fever associated to arthritis.
AB  - We describe the first Brazilian case of mild Rickettsiosis, complicated by knee
      monoarthritis, in young adult bitten by a tick on his left leg in Camburi zone,
      located in Sao Sebastiao municipality, southern coastal region of the State of
      Sao Paulo, in the Atlantic rainforest region, Brazil. The patient developed
      inoculation eschar at the tick bite site associated with enlarged lymph nodes in
      the left groin, fever, polyarthralgia, headache and macular rash. Twenty days
      after tick bite episode, he displayed monoarthritis in his right knee. The
      diagnosis of mild Rickettsiosis was established by sequential immunological
      analysis in serum and synovial fluid, using the indirect immunofluorescence (IF)
      assay for antibodies reactive with Rickettsia parkeri and Rickettsia rickettsii.
      The mild Rickettsiosis is an emerging zoonosis, that must be investigated by
      physicians, including rheumatologists, in patients that present macular rash,
      fever and eventually arthritis, after visiting the southern coastal Atlantic
      rainforest region in Brazil. 

PMID- 25054605
TI  - When anti-TNF fails, anti-IL12-23 is an alternate option in psoriasis and
      psoriatic arthritis.
AB  - Patients with psoriasis and psoriatic arthritis respond to anti-TNF therapy, but
      not all patients maintain effective response, and some do not respond. In this
      article, we demonstrate the role of a new pathogenetic pathway to some extent TNF
      independent in these patients. Anti-IL12-23 is a new and alternate mode of
      therapy for patients with recalcitrant response to anti-TNF. 

PMID- 25054604
TI  - Patients with systemic lupus erythematosus and secondary antiphospholipid
      syndrome have decreased numbers of circulating CD4+CD25+Foxp3+ Treg and CD3-CD19+
      B cells.
AB  - INTRODUCTION: CD4+CD25+Foxp3+ regulatory T (Treg) cell depletion has been
      reported in systemic lupus erythematosus (SLE) and, recently, in primary
      antiphospholipid syndrome (APS); the issue has not been studied in SLE patients
      with secondary APS (SLE/APS) so far. OBJECTIVE: To quantify total lymphocytes,
      Treg cells, CD3+CD19- T cells and CD3-CD19+ B cells in SLE/APS patients and
      healthy controls. METHODS: Cell subtypes underwent immunophenotyping using
      specific monoclonal antibodies (anti-CD3 CY5, anti-CD4 FITC, anti-CD25, anti
      Foxp3, anti-CD19 PE) and flow cytometry. RESULTS: Twenty-five patients with
      SLE/APS (mean age 43.5 years, 96% females, 96% caucasians, mean duration of
      disease 9.87 years, mean SLEDAI 10 +/- 5.77) and 25 age and sex-matched controls
      entered the study. It was realized that the numbers of Treg and CD3- CD19+ B
      cells were significantly lower in SLE/APS patients than in controls (all p <
      0.05).Treg and CD3-CD19+ B cells remained numerically low after controlling
      (ANCOVA) for percentage of total lymphocytes (p < 0.05). Decreasing levels of
      circulating Treg and CD3-CD19+ B cells correlated to higher scores of lupus
      activity (rs = -0.75, p < 0.0001; rs = -0.46, p = 0.021, respectively). Number of
      Treg cells and CD3-CD19+ B lymphocytes did not significantly differ in users or
      nonusers of chloroquine, azathioprine and corticosteroids (all p > 0.05).
      CONCLUSIONS: In this preliminary study, patients with SLE and secondary APS
      showed depletion of Treg and CD3-CD19+ B cells; decreasing numbers of both
      subtypes correlated to a higher SLEDAI. Treg cells depletion might contribute to
      the autoimmune lesion seen in patients with SLE/APS. The reduced number of CD3
      CD19+ B cells seen in these patients deserves more studies in order to get
      further elucidation.

PMID- 25054606
TI  - Articular ultrasonography: interobserver reliability in rheumatoid arthritis.
AB  - INTRODUCTION: Ultrasonography (US) has a recent use in Rheumatology, and the
      reliability of the method in rheumatoid arthritis (RA) patients has yet to be
      clarified. OBJECTIVE: To test, in a RA survey, the reproducibility of
      musculoskeletal US performed by rheumatologists with one-year training through re
      analysis by a Rheumatologist experienced in the method. PATIENTS AND METHODS:
      This cross-sectional study included consecutive RA patients from our tertiary
      center. US exam was performed in metacarpophalangeal joints, proximal
      interphalangeal joints, and wrists. Presence of synovitis, power Doppler (PD)
      signal, bone erosions, and cartilage changes comprised the US parameters
      evaluated. A kappa value in-between 0.20 and 0.40 was considered fair; in-between
      0.41 and 0.60 was moderate; in-between 0.61 and 0.80 was good; and above 0.81 was
      excellent. RESULTS: We analyzed 1,380 joints of 60 RA patients (78% females, 78%
      caucasoids). Mean age was 58 +/- 11.56 years, mean disease duration was 9.98 +/-
      7.79 years, mean DAS28 was 3.82 +/- 1.53, and mean HAQ was 0.91 +/- 0.67. Kappa
      agreement for synovitis ranged from 0.30 to 0.70; for PD signal, from 0.53 to
      absolute agreement; for erosions, from 0.70 to 0.97; for cartilage changes, from
      0.28 to 0.63. CONCLUSION: Although good, moderate and excellent interobserver
      agreement were obtained for erosions and PD, concordance for synovitis and
      cartilage changes were less impressive in our patients with active RA. Further
      studies on standardization of scanning technique are necessary to improve
      musculoskeletal US reproducibility.

PMID- 25054607
TI  - Retraction. Anti-citrullinated peptide antibodies and rheumatoid factor in
      Sudanese patients with Leishmania donovani infection.

PMID- 25054609
TI  - Health reform and changes in health insurance coverage in 2014.

PMID- 25054610
TI  - Highly enantioselective hydrogenation of steric hindrance enones catalyzed by Ru
      complexes with chiral diamine and achiral phosphane.
AB  - An asymmetric hydrogenation of sterically hindered beta,beta-disubstituted enones
      has been well-established by using a ruthenium complex composed of an achiral
      diphosphane and a chiral diamine as catalyst, wherein the carbonyl group was
      selectively hydrogenated to give a wide range of chiral allylic alcohols with
      high levels of enantioselectivity and complete chemoselectivity. 

PMID- 25054611
TI  - Minimizing the 1/r(2) perturbation for ideal fluence detectors in small source
      gamma-irradiation fields.
AB  - A technique for analyzing the effect of the geometrical shape of a source or a
      detector, using a quadrupole expansion, is described herein. It is shown that
      this method may be exploited to predict, optimize the geometry of a source, or a
      measurement device, and nearly eliminate, the departure from the 1/r(2) fall-off
      characteristic due to irradiation from small sources. We have investigated
      several simple shapes that have a vanishing Q2 quadrupole moment: a right
      circular cylinder with a diameter to depth ratio of ?[2], a cone with a radius to
      height ratio of unity, and an oblate ellipsoid with a diameter to depth ratio of
      ?[3/2]. These ideal shapes produce optimally small departures in a 1/r(2) field,
      nearly mimicking a point-like detector. We have also found a rotationally
      symmetric shape, intermediate to the other three, that has additionally, a
      vanishing Q4, the hexadecapole moment. This geometry further improves the 1/r(2)
      perturbation characteristics and has an additional free parameter that may be
      adjusted to model the ideal cylinder, cone or oblate spheroid.

PMID- 25054612
TI  - In vitro antioxidant capacity of tea of Echinodorus grandiforus, "leather hat,"
      in Wistar rat liver.
AB  - Oxidative stress has been considered as one of the factors responsible for
      hepatic diseases, which sometimes require new ways of treatment. The present
      study aimed to evaluate the in vitro antioxidant capacity of the tea of
      Echinodorus grandiforus ("leather hat" plant) in rat liver. Different
      preparations of tea were evaluated for phenolic composition, antioxidant activity
      by DPPH assay and ability to inhibit lipid peroxidation induced by copper
      sulfate. The antioxidant activity was assessed in liver tissue treated with
      sodium azide in the presence or absence of tea by assays for lipid peroxidation
      (TBARS), protein oxidation (carbonyl) and the antioxidant enzymes catalase (CAT)
      and superoxide dismutase (SOD). The results show that different preparations of
      tea are important sources of polyphenols and contain theobromine, catechin and
      vitexin. Furthermore, the results indicate that this tea exhibits an antioxidant
      activity by its ability to scavenge DPPH radical. Different preparations of tea
      prevented damage to lipids and proteins induced by sodium azide, as well as
      assisting in restoring CAT and SOD activities. Thus, it can be seen that E.
      grandiforus tea had antioxidant activity in serum and liver being able to prevent
      oxidative damages generated by sodium azide. 

PMID- 25054614
TI  - Indentation and self-healing mechanisms of a self-assembled monolayer--a combined
      experimental and modeling study.
AB  - A combination of in situ vibrational sum-frequency generation (SFG) spectroscopy
      and molecular-dynamics (MD) simulations has allowed us to study the effects of
      indentation of self-assembled octadecylphosphonic acid (ODPA) monolayers on alpha
      Al2O3(0001). Stress-induced changes in the vibrational signatures of C-H
      stretching vibrations in SFG spectra and the results of MD simulations provide
      clear evidence for an increase in gauche-defect density in the monolayer as a
      response to indentation. A stress-dependent analysis indicates that the defect
      density reaches saturation at approximately 155 MPa. After stress is released,
      the MD simulations show an almost instantaneous healing of pressure-induced
      defects in good agreement with experimental results. The lateral extent of the
      contact areas was studied with colocalized SFG spectroscopy and compared to
      theoretical predictions for pressure gradients from Hertzian contact theory. SFG
      experiments reveal a gradual increase in gauche-defect density with pressure
      before saturation close to the contact center. Furthermore, our MD simulations
      show a spatial anisotropy of pressure-induced effects within ODPA domains:
      molecules tilted in the direction of the pressure gradient increase in tilt angle
      while those on the opposite side form gauche-defects. 

PMID- 25054615
TI  - One-pot synthesis of 1,4-disubstituted pyrazoles from arylglycines via copper
      catalyzed sydnone-alkyne cycloaddition reaction.
AB  - A robust method for constructing 1,4-pyrazoles from arylglycines was developed
      using the copper-catalyzed sydnone-alkyne cycloaddition reaction. The procedure
      offers a straightforward and general route to the pyrazole heterocycle through a
      three-step one-pot procedure. 

PMID- 25054616
TI  - Characterization by Deep Sequencing of Prunus virus T, a Novel Tepovirus
      Infecting Prunus Species.
AB  - Double-stranded RNAs purified from a cherry tree collected in Italy and a plum
      tree collected in Azerbaijan were submitted to deep sequencing. Contigs showing
      weak but significant identity with various members of the family Betaflexiviridae
      were reconstructed. Sequence comparisons led to the conclusion that the viral
      isolates identified in the analyzed Prunus plants belong to the same viral
      species. Their genome organization is similar to that of some members of the
      family Betaflexiviridae, with three overlapping open reading frames (RNA
      polymerase, movement protein, and capsid protein). Phylogenetic analyses of the
      deduced encoded proteins showed a clustering with the sole member of the genus
      Tepovirus, Potato virus T (PVT). Given these results, the name Prunus virus T
      (PrVT) is proposed for the new virus. It should be considered as a new member of
      the genus Tepovirus, even if the level of nucleotide identity with PVT is
      borderline with the genus demarcation criteria for the family Betaflexiviridae. A
      reverse-transcription polymerase chain reaction detection assay was developed and
      allowed the identification of two other PrVT isolates and an estimate of 1%
      prevalence in the large Prunus collection screened. Due to the mixed infection
      status of all hosts identified to date, it was not possible to correlate the
      presence of PrVT with specific symptoms.

PMID- 25054617
TI  - Evaluation of a Diverse, Worldwide Collection of Wild, Cultivated, and Landrace
      Pepper (Capsicum annuum) for Resistance to Phytophthora Fruit Rot, Genetic
      Diversity, and Population Structure.
AB  - Pepper is the third most important solanaceous crop in the United States and
      fourth most important worldwide. To identify sources of resistance for commercial
      breeding, 170 pepper genotypes from five continents and 45 countries were
      evaluated for Phytophthora fruit rot resistance using two isolates of
      Phytophthora capsici. Genetic diversity and population structure were assessed on
      a subset of 157 genotypes using 23 polymorphic simple sequence repeats. Partial
      resistance and isolate-specific interactions were identified in the population at
      both 3 and 5 days postinoculation (dpi). Plant introductions (PIs) 640833 and
      566811 were the most resistant lines evaluated at 5 dpi to isolates 12889 and
      OP97, with mean lesion areas less than Criollo de Morelos. Genetic diversity was
      moderate (0.44) in the population. The program STRUCTURE inferred four genetic
      clusters with moderate to very great differentiation among clusters. Most lines
      evaluated were susceptible or moderately susceptible at 5 dpi, and no lines
      evaluated were completely resistant to Phytophthora fruit rot. Significant
      population structure was detected when pepper varieties were grouped by
      predefined categories of disease resistance, continent, and country of origin.
      Moderately resistant or resistant PIs to both isolates of P. capsici at 5 dpi
      were in genetic clusters one and two.

PMID- 25054618
TI  - (44)Sc: an attractive isotope for peptide-based PET imaging.
AB  - The overexpression of integrin alphavbeta3 has been linked to tumor
      aggressiveness and metastasis in several cancer types. Because of its high
      affinity, peptides containing the arginine-glycine-aspartic acid (RGD) motif have
      been proven valuable vectors for noninvasive imaging of integrin alphavbeta3
      expression and for targeted radionuclide therapy. In this study, we aim to
      develop a (44)Sc-labeled RGD-based peptide for in vivo positron emission
      tomography (PET) imaging of integrin alphavbeta3 expression in a preclinical
      cancer model. High quality (44)Sc (t1/2, 3.97 h; beta(+) branching ratio, 94.3%)
      was produced inexpensively in a cyclotron, via proton irradiation of natural Ca
      metal targets, and separated by extraction chromatography. A dimeric cyclic-RGD
      peptide, (cRGD)2, was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA) and radiolabeled with (44)Sc in high yield (>90%) and
      specific activity (7.4 MBq/nmol). Serial PET imaging of mice bearing U87MG tumor
      xenografts showed elevated (44)Sc-DOTA-(cRGD)2 uptake in the tumor tissue of 3.93
      +/- 1.19, 3.07 +/- 1.17, and 3.00 +/- 1.25 %ID/g at 0.5, 2, and 4 h
      postinjection, respectively (n = 3), which were validated by ex vivo
      biodistribution experiments. The integrin alphavbeta3 specificity of the tracer
      was corroborated, both in vitro and in vivo, by competitive cell binding and
      receptor blocking assays. These results parallel previously reported studies
      showing similar tumor targeting and pharmacokinetic profiles for dimeric cRGD
      peptides labeled with (64)Cu or (68)Ga. Our findings, together with the
      advantageous radionuclidic properties of (44)Sc, capitalize on the relevance of
      this isotope as an attractive alternative isotope to more established radiometals
      for small molecule-based PET imaging, and as imaging surrogate of (47)Sc in
      theranostic applications. 

PMID- 25054621
TI  - Proper surface termination for luminescent near-surface NV centers in diamond.
AB  - By accurate quantum mechanical simulations, we show that typical diamond surfaces
      possess image states with sub-bandgap energies, and compromise the photostability
      of NV centers placed within a few nm of the surface. This occurs due to the
      mixture of the NV-related gap states and the surface image states, which is a
      novel and distinct process from the well-established band bending effect. We also
      find that certain types of coverages on the diamond surface may lead to blinking
      or bleaching due to the presence of acceptor surface states. We identify a
      combination of surface terminators that is perfect for NV-center based nanoscale
      sensing. 

PMID- 25054620
TI  - Melanocytic galectin-3 is associated with tyrosinase-related protein-1 and
      pigment biosynthesis.
AB  - Galectin-3 is a family member of the carbohydrate-binding proteins widely
      expressed by many cell types and exhibits multiple cellular functions. We
      demonstrate that melanocytes express galectin-3, which is predominantly localized
      to the cell body peripherally along the Golgi zone. Downregulation of galectin-3
      in human melanocytes using short hairpin RNA technology resulted in the reduction
      of both melanin synthesis and expression/activity of tyrosinase-related protein-1
      (Tyrp-1). In the cell body, galectin-3 colocalizes with melanosome-destined
      cargo, specifically tyrosinase and Tyrp-1. We studied melanocytes cultured from
      patients with forms of Hermansky-Pudlak syndrome (HPS) containing defects in
      trafficking steps governed by biogenesis of lysosome-related organelle complex-2
      (BLOC-2) (HPS-5), BLOC-3 (HPS-1), and adaptin-3 (HPS-2). We found that galectin-3
      expression mimicked the defective expression of the tyrosinase cargo in dendrites
      of HPS-5 melanocytes, but it was not altered in HPS-1 or HPS-2 melanocytes. In
      addition, galectin-3 colocalized predominantly with the HPS-5 component of BLOC-2
      in normal human melanocytes. These data indicate that galectin-3 is a regulatory
      component in melanin synthesis affecting the expression of Tyrp-1. 

PMID- 25054622
TI  - The synthesis of organic charge transfer hetero-microtubules by crack welding.
AB  - The strain-induced cracks in organic microtubules composed of an organic charge
      transfer (CT) complex of 1,2,4,5-tetracyanobenzene (TCNB) and naphthalene were
      selectively welded via the formation of secondary CT complexes; this process, in
      turn, led to the formation of organic hetero-microtubules consisting of multiple
      segments of two organic CT complexes. 

PMID- 25054624
TI  - A role of disordered domains in regulating protein oligomerization and stability.
AB  - Intrinsically disordered proteins (IDPs) or regions (IDRs) in proteins hold many
      functions but their biological roles are still not fully understood. Here we
      describe a new role of such regions. Using the HIV-1 Rev protein, we show that
      disordered domains have a role in maintaining the correct oligomeric state and
      the thermodynamic stability of proteins. 

PMID- 25054623
TI  - Coevolutionary immune system dynamics driving pathogen speciation.
AB  - We introduce and analyze a within-host dynamical model of the coevolution between
      rapidly mutating pathogens and the adaptive immune response. Pathogen mutation
      and a homeostatic constraint on lymphocytes both play a role in allowing the
      development of chronic infection, rather than quick pathogen clearance. The
      dynamics of these chronic infections display emergent structure, including
      branching patterns corresponding to asexual pathogen speciation, which is
      fundamentally driven by the coevolutionary interaction. Over time, continued
      branching creates an increasingly fragile immune system, and leads to the
      eventual catastrophic loss of immune control. 

PMID- 25054625
TI  - Prediction of antidepressant response to venlafaxine by a combination of early
      response assessment and therapeutic drug monitoring.
AB  - INTRODUCTION: Early assessment of a therapeutic response is a central goal in
      antidepressant treatment. The present study examined the potential for
      therapeutic drug monitoring and symptom rating to predict venlafaxine treatment
      efficacy (measured by overall patient response and remission). METHODS: 88
      patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum
      concentrations of venlafaxine (VEN) and its active metabolite O
      desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric
      ratings were measured for up to 6 weeks by independent study raters. RESULTS: An
      early improvement was significantly more common in venlafaxine responders than
      non-responders (chi(2); p=0.007). While ODV serum levels were significantly
      higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV
      and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early
      response combined with an ODV serum level above the median of 222 ng/mL were
      significantly more likely to achieve full response (binary logistic model;
      p<0.01). Sensitivity (84% for early response) and specificity (81% for
      combination of early response and therapeutic drug monitoring) were sufficient to
      qualify as a reasonable screening instrument. CONCLUSION: Our results indicate
      that early improvement and ODV serum concentration are predictive of therapeutic
      outcome and can thus be used to guide use of the antidepressant venlafaxine.

PMID- 25054626
TI  - Production and evaluation of recombinant granule antigen protein GRA7 for
      serodiagnosis of Toxoplasma gondii infection in cattle.
AB  - The precise detection of Toxoplasma gondii infection in cattle has important
      public health significance. In the present study, recombinant granule antigen
      protein GRA7 was evaluated as a potential diagnostic marker for T. gondii
      infection in cattle by an indirect enzyme-linked immunosorbent assay (ELISA)
      using the reference serum samples determined by immunofluorescence assay and
      Western blotting, showing that GRA7-ELISA has a sensitivity of 96.4%, and a
      specificity of 98.6%. The detection results by GRA7- and Toxoplasma lysate
      antigen-based ELISAs were compared, indicating that no significant difference
      (p>0.05) and perfect agreement (kappa=0.74) was observed between the two tests.
      Receiver operating characteristic analysis showed a relative sensitivity and
      specificity of 100% and 97.3% at the cut-off value of 0.3 for GRA7-ELISA. These
      data demonstrate that GRA7 is a promising serodiagnostic marker for T. gondii
      infection in cattle.

PMID- 25054627
TI  - Identifying keystone species in the human gut microbiome from metagenomic
      timeseries using sparse linear regression.
AB  - Human associated microbial communities exert tremendous influence over human
      health and disease. With modern metagenomic sequencing methods it is now possible
      to follow the relative abundance of microbes in a community over time. These
      microbial communities exhibit rich ecological dynamics and an important goal of
      microbial ecology is to infer the ecological interactions between species
      directly from sequence data. Any algorithm for inferring ecological interactions
      must overcome three major obstacles: 1) a correlation between the abundances of
      two species does not imply that those species are interacting, 2) the sum
      constraint on the relative abundances obtained from metagenomic studies makes it
      difficult to infer the parameters in timeseries models, and 3) errors due to
      experimental uncertainty, or mis-assignment of sequencing reads into operational
      taxonomic units, bias inferences of species interactions due to a statistical
      problem called "errors-in-variables". Here we introduce an approach, Learning
      Interactions from MIcrobial Time Series (LIMITS), that overcomes these obstacles.
      LIMITS uses sparse linear regression with boostrap aggregation to infer a
      discrete-time Lotka-Volterra model for microbial dynamics. We tested LIMITS on
      synthetic data and showed that it could reliably infer the topology of the inter
      species ecological interactions. We then used LIMITS to characterize the species
      interactions in the gut microbiomes of two individuals and found that the
      interaction networks varied significantly between individuals. Furthermore, we
      found that the interaction networks of the two individuals are dominated by
      distinct "keystone species", Bacteroides fragilis and Bacteroided stercosis, that
      have a disproportionate influence on the structure of the gut microbiome even
      though they are only found in moderate abundance. Based on our results, we
      hypothesize that the abundances of certain keystone species may be responsible
      for individuality in the human gut microbiome. 

PMID- 25054628
TI  - The spectrum of major seed storage genes and proteins in oats (Avena sativa).
AB  - BACKGROUND: The oat seed storage proteins are mainly composed of two classes: the
      globulins and avenins. Among the major cereals, the globulins are the major seed
      protein class in rice and oats, and along with the higher protein content of oats
      is the basis for the relative higher nutrition content in oats compared to the
      other cereals. The second major class of oat seed proteins is the avenins; also
      classified as prolamins - seed proteins high in proline and glutamine amino
      acids. The prolamins are associated with celiac disease, an autoimmune disorder
      of the gastrointestinal tract. In spite of their importance, neither the oat
      globulins nor the avenins have been completely analyzed and described for any
      single germplasm. RESULTS: Using available EST resources for a single hexaploid
      oat cultivar, the spectrum of avenin and globulin sequences are described for the
      gene coding regions and the derived protein sequences. The nine unique avenin
      sequences are suggested to be divided into 3-4 distinct subclasses distributed in
      the hexaploid genome. The globulins from the same germplasm include 24 distinct
      sequences. Variation in globulin size results mainly from a glutamine-rich
      domain, similar to as in the avenins, and to variation in the C-terminal sequence
      domain. Two globulin genes have premature stop codons that shorten the resulting
      polypeptides by 9 and 17 amino acids, and eight of the globulin sequences form a
      branch of the globulins not previously reported. CONCLUSIONS: A more complete
      description of the major oat seed proteins should allow a more thorough analysis
      of their contributions to those oat seed characteristics related to nutritional
      value, evolutionary history, and celiac disease association.

PMID- 25054629
TI  - An oral phosphodiesterase inhibitor (apremilast) for inflammatory rosacea in
      adults: a pilot study.

PMID- 25054631
TI  - Bio-inspired micro-fluidic angular-rate sensor for vestibular prostheses.
AB  - This paper presents an alternative approach for angular-rate sensing based on the
      way that the natural vestibular semicircular canals operate, whereby the inertial
      mass of a fluid is used to deform a sensing structure upon rotation. The
      presented gyro has been fabricated in a commercially available MEMS process,
      which allows for microfluidic channels to be implemented in etched glass layers,
      which sandwich a bulk-micromachined silicon substrate, containing the sensing
      structures. Measured results obtained from a proof-of-concept device indicate an
      angular rate sensitivity of less than 1  degrees /s, which is similar to that of
      the natural vestibular system. By avoiding the use of a continually-excited
      vibrating mass, as is practiced in today's state-of-the-art gyroscopes, an ultra
      low power consumption of 300 MUW is obtained, thus making it suitable for
      implantation. 

PMID- 25054632
TI  - A large response range reflectometric urea biosensor made from silica-gel
      nanoparticles.
AB  - A new silica-gel nanospheres (SiO2NPs) composition was formulated, followed by
      biochemical surface functionalization to examine its potential in urea biosensor
      development. The SiO2NPs were basically synthesized based on sol-gel chemistry
      using a modified Stober method. The SiO2NPs surfaces were modified with amine (
      NH2) functional groups for urease immobilization in the presence of glutaric acid
      (GA) cross-linker. The chromoionophore pH-sensitive dye ETH 5294 was physically
      adsorbed on the functionalized SiO2NPs as pH transducer. The immobilized urease
      determined urea concentration reflectometrically based on the colour change of
      the immobilized chromoionophore as a result of the enzymatic hydrolysis of urea.
      The pH changes on the biosensor due to the catalytic enzyme reaction of
      immobilized urease were found to correlate with the urea concentrations over a
      linear response range of 50-500 mM (R2 = 0.96) with a detection limit of 10 mM
      urea. The biosensor response time was 9 min with reproducibility of less than 10%
      relative standard deviation (RSD). This optical urea biosensor did not show
      interferences by Na+, K+, Mg2+ and NH4+ ions. The biosensor performance has been
      validated using urine samples in comparison with a non-enzymatic method based on
      the use of p-dimethylaminobenzaldehyde (DMAB) reagent and demonstrated a good
      correlation between the two different methods (R2 = 0.996 and regression slope of
      1.0307). The SiO2NPs-based reflectometric urea biosensor showed improved dynamic
      linear response range when compared to other nanoparticle-based optical urea
      biosensors. 

PMID- 25054633
TI  - Small infrared target detection by region-adaptive clutter rejection for sea
      based infrared search and track.
AB  - This paper presents a region-adaptive clutter rejection method for small target
      detection in sea-based infrared search and track. In the real world, clutter
      normally generates many false detections that impede the deployment of such
      detection systems. Incoming targets (missiles, boats, etc.) can be located in the
      sky, horizon and sea regions, which have different types of clutters, such as
      clouds, a horizontal line and sea-glint. The characteristics of regional clutter
      were analyzed after the geometrical analysis-based region segmentation. The false
      detections caused by cloud clutter were removed by the spatial attribute-based
      classification. Those by the horizontal line were removed using the heterogeneous
      background removal filter. False alarms by sun-glint were rejected using the
      temporal consistency filter, which is the most difficult part. The experimental
      results of the various cluttered background sequences show that the proposed
      region adaptive clutter rejection method produces fewer false alarms than that of
      the mean subtraction filter (MSF) with an acceptable degradation detection rate. 

PMID- 25054634
TI  - Lasting treatment effects in a postmarketing surveillance study of prolonged
      release melatonin.
AB  - Surveillance studies are useful to evaluate how a new medicinal product performs
      in everyday treatment and how the patient who takes it feels and functions,
      thereby determining the benefit/risk ratio of the drug under real-life
      conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe
      for the management of primary insomnia patients age 55 years or older suffering
      from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine
      receptor agonists), there are concerns about rebound insomnia and/or withdrawal
      symptoms. We report data from a postmarketing surveillance study in Germany on
      the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia
      during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In
      total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7
      years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the
      mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad)
      improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The
      improvements persisted over the post-treatment observation period. Rebound
      insomnia, defined as a one-point deterioration in sleep quality below baseline
      values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of
      the patients (77%) who used traditional hypnotics before PRM treatment had
      stopped using them and only 5.6% of naive patients started such drugs after PRM
      discontinuation. PRM was well tolerated during treatment and the most frequently
      reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness
      and headache (five patients each, <1%). There were no serious adverse events and
      no adverse events were reported after discontinuation. The persisting treatment
      effect and very low rebound rate suggest a beneficial role of sleep-wake cycle
      stabilization with PRM in the treatment of insomnia. 

PMID- 25054635
TI  - Indigenous knowledge and science unite to reveal spatial and temporal dimensions
      of distributional shift in wildlife of conservation concern.
AB  - Range shifts among wildlife can occur rapidly and impose cascading ecological,
      economic, and cultural consequences. However, occurrence data used to define
      distributional limits derived from scientific approaches are often outdated for
      wide ranging and elusive species, especially in remote environments. Accordingly,
      our aim was to amalgamate indigenous and western scientific evidence of grizzly
      bear (Ursus arctos horribilis) records and detail a potential range shift on the
      central coast of British Columbia, Canada. In addition, we test the hypothesis
      that data from each method yield similar results, as well as illustrate the
      complementary nature of this coupled approach. Combining information from
      traditional and local ecological knowledge (TEK/LEK) interviews with remote
      camera, genetic, and hunting data revealed that grizzly bears are now present on
      10 islands outside their current management boundary. LEK interview data
      suggested this expansion has accelerated over the last 10 years. Both approaches
      provided complementary details and primarily affirmed one another: all islands
      with scientific evidence for occupation had consistent TEK/LEK evidence.
      Moreover, our complementary methods approach enabled a more spatially and
      temporally detailed account than either method would have afforded alone. In many
      cases, knowledge already held by local indigenous people could provide timely and
      inexpensive data about changing ecological processes. However, verifying the
      accuracy of scientific and experiential knowledge by pairing sources at the same
      spatial scale allows for increased confidence and detail. A similarly coupled
      approach may be useful across taxa in many regions. 

PMID- 25054636
TI  - A meta-analysis of experiments linking incubation conditions with subsequent leg
      weakness in broiler chickens.
AB  - A series of incubation and broiler growth studies were conducted using one strain
      of broiler chicken (fast feathering dam line) observing incubation effects on
      femoral bone ash % at hatch and the ability of the bird to remain standing at 6
      weeks of age (Latency-To-Lie). Egg shell temperatures during incubation were
      consistently recorded. Parsimonious models were developed across eight studies
      using stepwise multiple linear regression of egg shell temperatures over 3-day
      periods and both bone ash at hatch and Latency-To-Lie. A model for bone ash at
      hatch explained 70% of the variation in this factor and revealed an association
      with lower egg shell temperatures during days 4-6 and 13-15 and higher egg shell
      temperatures during days 16-18 of incubation. Bone ash at hatch and subsequent
      Latency-To-Lie were positively correlated (r = 0.57, P<0.05). A model described
      66% of the variation Latency-To-Lie showing significant association of the
      interaction of femoral ash at hatch and lower average egg shell temperatures over
      the first 15 days of incubation. Lower egg shell temperature in the early to mid
      incubation process (days 1-15) and higher egg shell temperatures at a later stage
      (days 16-18) will both tend to delay the hatch time of incubating eggs.
      Incubation profiles that resulted in later hatching chicks produced birds which
      could remain standing for a longer time at 6 weeks of age. This supports a
      contention that the effects of incubation observed in many studies may in fact
      relate more to earlier hatching and longer sojourn of the hatched chick in the
      final stage incubator. The implication of these outcomes are that the optimum egg
      shell temperature during incubation for broiler leg strength development may be
      lower than that regarded as ideal (37.8 degrees C) for maximum hatchability and
      chick growth. 

PMID- 25054637
TI  - Au@Ag core/shell nanoparticles as colorimetric probes for cyanide sensing.
AB  - We synthesize Au@Ag core/shell nanoparticles (NPs) using a Au NP assisted Tollens
      reaction. The as-synthesized NPs are used for the colorimetric cyanide sensing
      with a detection limit of 0.4 MUM. The bimetallic NPs are immobilized into
      agarose gels as portable "test strips". 

PMID- 25054638
TI  - Methane activation by laser-ablated Th atoms: matrix infrared spectra and
      theoretical investigations of CH3-Th-H and CH2?ThH2.
AB  - Methane activation by laser-ablated Th atoms on the triplet potential energy
      surface produces the methylthorium hydride, CH3-Th-H, that converts smoothly by
      alpha-H transfer to CH2-ThH2, which relaxes in the matrix to the more stable
      singlet methylidene, CH2?ThH2. This first actinide methylidene was characterized
      from argon matrix infrared spectra and B3LYP calculations in our laboratory. We
      now report neon matrix investigations, which include the methylthorium hydride
      and the Th-D stretching modes of CD2?ThD2 that are blue-shifted in neon from
      under the intense CD4 precursor absorption, and reactions with CH2D2 that give
      rise to the CHD?ThHD modifications and their alpha-H and alpha-D transfer
      counterparts CD2?ThH2 and CH2?ThD2. New intrinsic reaction coordinate
      calculations show that this reaction proceeds smoothly on the triplet potential
      energy surface. 

PMID- 25054640
TI  - Spatial abilities and aging: a meta-analysis.
AB  - BACKGROUND/STUDY CONTEXT: Age-related effects in performance on spatial tasks
      have been well documented, with results suggesting a negative effect on
      performance in older samples. Although meta-analyses have been conducted
      examining performance on specific spatial tasks, it appears that data
      incorporating a variety of tasks have not yet been integrated into a single meta
      analyses. METHODS: The present study examined age-related effects on spatial
      abilities in a multilevel meta-analysis of 137 effect sizes, drawn from 80
      samples dated between 1958 and 2011. In addition to sample characteristics
      (education, year of publication, and age range), procedural factors (spatial
      ability category, spatial task, dependent variable, task setting, and medium of
      administration) were also considered. The standardized mean difference (Cohen's
      d) was used as the effect size measure in meta-analytic calculations. RESULTS:
      RESULTS revealed a large (mean d = 1.01) age-related decrease in spatial
      performance on psychometric tests. Specifically, older adults (mean age range =
      63-79.5 years) performed worse on psychometric tests than younger adults (mean
      age range = 17-28.6 years). Interestingly, this age effect was unaffected by
      factors such as specific test, test category (mental rotation, spatial
      perception, or spatial visualization), timing conditions, and group or individual
      administration. However, measures of response time produced significantly larger
      effects of age than measures of accuracy on spatial performance. CONCLUSION: The
      present analysis demonstrates a clear pattern of negative age effects in spatial
      ability across the literature. Although these effects are unaffected by the
      specific spatial component under investigation or testing conditions, speed of
      processing was shown to be an important factor in spatial performance. The need
      to report more thoroughly on characteristics of young and old participants in
      future studies is also emphasized.

PMID- 25054639
TI  - T-cells null for the MED23 subunit of mediator express decreased levels of KLF2
      and inefficiently populate the peripheral lymphoid organs.
AB  - MED23, a subunit of the Mediator coactivator complex, is important for the
      expression of a subset of MAPK/ERK pathway-responsive genes, the constituents of
      which vary between cell types for reasons that are not completely clear. MAPK/ERK
      pathway-dependent processes are essential for T-cell development and function,
      but whether MED23 has a role in this context is unknown. We generated Med23
      conditional knockout mice and induced Med23 deletion in early T-cell development
      using the lineage specific Lck-Cre transgene. While the total cell number and
      distribution of cell populations in the thymuses of Med23flox/flox;Lck-Cre mice
      were essentially normal, MED23 null T-cells failed to efficiently populate the
      peripheral lymphoid organs. MED23 null thymocytes displayed decreased expression
      of the MAPK/ERK-responsive genes Egr1, Egr2, as well as of the membrane
      glycoprotein Cd52 (CAMPATH-1). MED23 null CD4 single-positive thymocytes also
      showed decreased expression of KLF2 (LKLF), a T-cell master regulatory
      transcription factor. Indeed, similarities between the phenotypes of mice lacking
      MED23 or KLF2 in T-cells suggest that KLF2 deficiency in MED23 null T-cells is
      one of their key defects. Mechanistic experiments using MED23 null MEFs further
      suggest that MED23 is required for full activity of the MAPK-responsive
      transcription factor MEF2, which has previously been shown to mediate Klf2
      expression. In summary, our data indicate that MED23 has critical roles in
      enabling T-cells to populate the peripheral lymphoid organs, possibly by
      potentiating MEF2-dependent expression of the T-cell transcription factor KLF2. 

PMID- 25054641
TI  - What will they think? The relationship between self-presentational concerns and
      balance and mobility outcomes in older women.
AB  - BACKGROUND/STUDY CONTEXT: Indirect evidence suggests that concerns over the
      impressions made on others (self-presentational concerns) may be associated with
      balance-related outcomes in older adults, but no empirical evidence exists to
      support this speculation. The present study examined the relationship between
      self-presentational concerns (social anxiety, social physique anxiety, and self
      presentational efficacy) and functional mobility, accounting for age, balance
      confidence, falls, and muscle strength. METHODS: Healthy women (60 years or
      older; N = 187) completed measures of self-presentational concerns, balance
      confidence, and fall history, and performed the timed up and go (TUG) test and a
      test of leg strength. Bivariate correlations were conducted. A hierarchical
      regression predicted TUG duration from the three self-presentational concerns,
      controlling for age, balance confidence, falls, and muscle strength to examine
      the unique variance in TUG duration explained by self-presentational concerns.
      RESULTS: Self-presentational efficacy was a significant predictor of TUG duration
      over and above that of age, balance confidence, falls, and muscle strength. The
      results also showed significant correlations between social anxiety and self
      presentational efficacy and TUG duration, between all three self-presentational
      concerns and balance confidence, and between social physique anxiety and self
      presentational efficacy and falls. CONCLUSIONS: Research is needed to examine the
      causal relationship between these outcomes. Investigating self-presentational
      concerns in older women may provide novel ways to impact balance-related outcomes
      in this population. Practical implications for clinicians are discussed, as the
      social and physical environment may influence self-presentational concerns in
      this population and subsequently impact assessment and treatment outcomes.

PMID- 25054642
TI  - Sentence comprehension in older adults: evidence for risky processing strategies.
AB  - BACKGROUND/STUDY CONTEXT: Previous research has suggested that older adults
      compensate for age-related declines in sentence comprehension ability by reading
      more slowly. The purpose of this study was to investigate the hypothesis that
      older adults adopt a riskier strategy than younger adults, in which they rely on
      expectations based on probabilistic cues. METHODS: Older and younger adults read
      late closure sentences in a self-paced reading task (e.g., "When the waiter
      served the woman the food was still too hot."). The subordinate verbs varied in
      whether or not they occurred in ditransitive constructions (served vs. kissed).
      RESULTS: Older adults showed less evidence of processing disruptions at the
      ambiguous noun phrase (the food) than younger adults. At the main verb, the older
      and younger adults showed evidence of processing disruption in the same
      conditions, but the processing disruptions were greater in older adults.
      CONCLUSION: The results are interpreted as support for the hypothesis that older
      adults adopt "risky" strategies during sentence comprehension.

PMID- 25054643
TI  - To what extent does the existence of functional relations in a learning setting
      change the pattern of differences between younger and older adults' performances?
AB  - BACKGROUND/STUDY CONTEXT: The study directly compared the learning performance of
      younger and older participants in two situations, one in which they had the
      possibility of detecting functional relations in the learning setting, and one in
      which they did not. Functional relations were defined as functional
      correspondences that could be established between abstract properties extracted
      from the sets of stimulus items and an abstract property extracted from the set
      of response items. METHODS: A total of 112 adults (18-90 years old) had to learn
      to predict the values of a numerical variable (the criterion) on the basis of two
      words (a plant and an animal) as cues. Five plants and five animals were graded
      according to size. The plant * animal design was orthogonal. The values of the
      criterion were obtained using an additive, linear scheme under the functional
      relations condition, and using random associations under the zero relations
      condition. RESULTS: The hypothesis was well supported by the data. In the absence
      of functional relations, the difference between younger and older participants'
      performances was shown to be practically as great as it could be in the
      experimental situation that was chosen. When functional relations were present,
      age differences were significantly reduced, to the extent that the performance of
      the older participants was almost as good as that achieved by the younger group.
      CONCLUSION: The existence of functional relations in a learning setting
      considerably changes the pattern of differences between younger and older adults'
      performance. In both the absence and the presence of functional relations, older
      and younger participants spontaneously approached the learning task in a
      functional spirit, and conceived a priori the cues and the criterion as directly
      related. Future studies should examine the way in which participants approach
      learning tasks, and the characteristics of the tasks that determine participants'
      spontaneous learning attitudes.

PMID- 25054644
TI  - Age and time effects on implicit and explicit learning.
AB  - BACKGROUND/STUDY CONTEXT: It has been proposed that effects of aging are more
      pronounced for explicit than for implicit motor learning. The authors evaluated
      this claim by comparing the efficacy of explicit and implicit learning of a
      movement sequence in young and older adults, and by testing the resilience
      against fatigue and secondary tasking after learning. It was also examined
      whether explicit learning in older adults can be promoted by alleviating time
      constraints during learning. METHODS: The alternating serial reaction time task
      (ASRTT) was used. Experiment 1 compared the benefits of receiving full
      instructions about the stimulus sequence relative to receiving no instructions in
      young (20-25 years) and older (50-65 years) adults during retention and during
      transfer to fatigue and secondary task conditions. Experiment 2 alleviated time
      constraints during the initial bouts of practice with full instructions. RESULTS:
      Experiment 1 indicated that the older adults learned on the ASRTT and achieved
      similar performance as young adults when no instructions were given. In contrast
      to the young adults, learning was not superior in older adults who received full
      instructions compared with those who did not. Experiment 2 indicated that
      alleviating time constraints allowed some of the older adults to gain from
      instruction but only under relatively low time constraints, but there was no
      retention with rigorous time constraints. CONCLUSION: Explicit learning, but not
      implicit learning, declines in older adults. This is partly due to older adults
      difficulties to apply explicit knowledge. Less rigorous time constraints can help
      to ameliorate some of these difficulties and may induce levels of explicit
      learning in older adults that will result in superior performance compared with
      implicit learning. Implicit learning did occur under time constraints that
      prevented explicit learning.

PMID- 25054645
TI  - Effects of silicon-limitation on growth and morphology of Triparma laevis NIES
      2565 (Parmales, Heterokontophyta).
AB  - The order Parmales (Heterokontophyta) is a group of small-sized unicellular
      marine phytoplankton, which is distributed widely from tropical to polar waters.
      The cells of Parmales are surrounded by a distinctive cell wall, which consists
      of several siliceous plates fitting edge to edge. Phylogenetic and morphological
      analyses suggest that Parmales is one of the key organisms for elucidating the
      evolutionary origin of Bacillariophyceae (diatoms), the most successful
      heterokontophyta. The effects of silicon-limitation on growth and morphogenesis
      of plates were studied using a strain of Triparma laevis NIES-2565, which was
      cultured for the first time in artificial sea water. The cells of T. laevis were
      surrounded by eight plates when grown with sufficient silicon. However, plate
      formation became incomplete when cells were cultured in a medium containing low
      silicate (ca. <10 uM). Cells finally lost almost all plates in a medium
      containing silicate concentrations lower than ca. 1 uM. However, silicon
      limitation did not affect growth rate; cells continued to divide without changing
      their growth rate, even after all plates were lost. Loss of plates was
      reversible; when cells without plates were transferred to a medium containing
      sufficient silicate, regeneration of shield and ventral plates was followed by
      the formation of girdle and triradiate plates. The results indicate that the
      response to silicon-limitation of T. laevis is different from that of diatoms,
      where cell division becomes inhibited under such conditions.

PMID- 25054646
TI  - Combined prevention for persons who inject drugs in the HIV epidemic in a
      transitional country: the case of Tallinn, Estonia.
AB  - The study was undertaken to assess the potential effectiveness of combined HIV
      prevention on the very high seroprevalence epidemic among persons who inject
      drugs (PWID) in Tallinn, Estonia, a transitional country. Data from community
      based cross-sectional (respondent-driven sampling) surveys of PWID in 2005, 2007,
      2009, and 2011 were used together with mathematical modeling of injection
      associated HIV acquisition to estimate changes in injection-related HIV incidence
      during these periods. Utilization of one, two, or three of the interventions
      available in the community (needle and syringes exchange program, antiretroviral
      treatment [ART], HIV testing, opioid substitution treatment) was reported by
      42.5%, 30.5%, and 11.5% of HIV+ and 34.7%, 36.4%, and 5.7% of HIV- PWIDs,
      respectively, in 2011. The modeling results suggest that the combination of
      needle/syringe programs and provision of ART to PWID in Tallinn substantially
      reduced the incidence of HIV infection in this population, from an estimated
      20.7/100 person-years in 2005 to 7.5/100 person-years in 2011. In conclusion,
      combined prevention targeting HIV acquisition and transmission-related risks
      among PWID in Tallinn has paralleled the downturn of the HIV epidemic in this
      population.

PMID- 25054647
TI  - Pigment epithelium-derived factor mediates impaired lung vascular development in
      neonatal hyperoxia.
AB  - Bronchopulmonary dysplasia is a chronic lung disease of preterm infants
      characterized by arrested microvascularization and alveolarization. Studies show
      the importance of proangiogenic factors for alveolarization, but the importance
      of antiangiogenic factors is unknown. We proposed that hyperoxia increases the
      potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs,
      inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-)
      mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from
      Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared
      with RA-exposed lungs (P < 0.05). In situ hybridization and immunofluorescence
      identified PEDF production primarily in alveolar epithelium. Hyperoxia reduced
      alveolarization in WT mice (P < 0.05) but not in PEDF(-/-) mice. WT hyperoxic
      mice had fewer platelet endothelial cell adhesion molecule (PECAM)-positive cells
      per alveolus (1.4 +/- 0.4) than RA-exposed mice (4.3 +/- 0.3; P < 0.05); this
      reduction was absent in hyperoxic PEDF(-/-) mice. The interactive regulation of
      lung microvascularization by vascular endothelial growth factor and PEDF was
      studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line.
      Vascular endothelial growth factor stimulation of proliferation, migration, and
      capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to
      conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in
      0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2
      cells cultured in RA (hyperoxia CM, 51 +/- 10% of RA CM, P < 0.05), an effect
      abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis
      and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely
      results from an altered balance between pro- and antiangiogenic factors. 

PMID- 25054649
TI  - The influence of kyphosis correction surgery on pulmonary function and thoracic
      volume.
AB  - STUDY DESIGN: A clinical study. OBJECTIVE: To measure the changes in pulmonary
      function and thoracic volume associated with surgical correction of kyphotic
      deformities. SUMMARY OF BACKGROUND DATA: No prior study has focused on the
      pulmonary function and thoracic cavity volume before and after corrective surgery
      for kyphosis. METHODS: Thirty-four patients with kyphosis underwent posterior
      deformity correction with instrumented fusion. Preoperative and postoperative
      pulmonary function was measured, and pulmonary function grade was evaluated as
      mild, significant, or severe. The change in preoperative to postoperative
      pulmonary function was analyzed, using 6 comparative subgroupings of patients on
      the basis of age, severity of kyphosis, location of kyphosis apex, length of
      follow-up time after surgery, degree of kyphosis correction, and number of
      segments fused. A second group of 19 patients also underwent posterior surgical
      correction of kyphosis, which had thoracic volume measured preoperatively and
      postoperatively with computed tomographic scanning. RESULTS: All of the pulmonary
      impairments were found to be restrictive. After surgery, most of the patients had
      improvement of the pulmonary function. Before surgery, the pulmonary function
      differences were found to be significant based on both severity of preoperative
      kyphosis (<60 degrees  vs. >60 degrees ) and location of the kyphosis apex (above
      T10 vs. below T10). Younger patients (younger than 35 yr) were more likely to
      exhibit statistically significant improvements in pulmonary function after
      surgery. However, thoracic volume was not significantly related to pulmonary
      function parameters. After surgery, average thoracic volume had no significant
      change. CONCLUSION: The major pulmonary impairment caused by kyphosis was found
      to be restrictive. Patients with kyphosis angle of 60 degrees  or greater or with
      kyphosis apex above T10 had more severe pulmonary dysfunction. Patients' age was
      significantly related to change in pulmonary function after surgery. However, the
      average thoracic volume had no significant change after surgery. LEVEL OF
      EVIDENCE: 3.

PMID- 25054648
TI  - A randomized clinical trial comparing extensible and inextensible lumbosacral
      orthoses and standard care alone in the management of lower back pain.
AB  - STUDY DESIGN: Single blinded, randomized clinical trial for the evaluation of
      lumbosacral orthoses (LSOs) in the management of lower back pain (LBP).
      OBJECTIVE: To evaluate the effects of two types of LSOs on self-rated disability
      in patients with LBP. SUMMARY OF BACKGROUND DATA: LSOs are commonly used for the
      management of LBP, but their effectiveness may vary because of design. An
      inextensible LSO (iLSO) reduces trunk motion and increases trunk stiffness,
      whereas an extensible LSO (eLSO) does not. METHODS: A total of 98 participants
      with LBP were randomized to 3 groups: (1) standard care (SC) group, which
      included medication and physical therapy (n = 29), (2) SC with eLSO (eLSO group)
      (n = 32), and (3) SC with iLSO (iLSO group) (n = 37). Outcome measures were
      evaluated before and after 2 weeks of treatment: modified Oswestry Disability
      Index (ODI), Patient Specific Activity Scale, pain ratings, and Fear Avoidance
      Beliefs Questionnaire. RESULTS: There were no statistically significant
      differences between groups at baseline. Compared with the SC alone, iLSO group
      showed greater improvement on the ODI scores (P = 0.01) but not the eLSO group.
      The ODI scores improved by a mean of 2.4 (95% confidence interval [CI], 2.2-7.1),
      8.1 (95% CI, 2.8-13.4), and 14.0 (95% CI, 8.2-19.8) points for SC, eLSO, and iLSO
      groups, respectively. Individuals wearing the iLSO had 4.7 times higher odds of
      achieving 50% or greater improvement in the ODI scores than those assigned to SC
      (95% CI, 1.2-18.5, P = 0.03). Both the eLSO and iLSO groups had a greater
      improvement in the Patient Specific Activity Scale scores than the SC group (P =
      .05 and P = 0.01, respectively), but the change did not meet the minimal
      clinically important difference. Pain ratings improved for all 3 groups, with no
      statistical difference between them. Finally, no significant differences across
      groups were found for the Fear Avoidance Beliefs Questionnaire. CONCLUSION: An
      iLSO led to greater improvement in ODI scores than SC and an eLSO. We surmise
      that the likely mechanism responsible for this difference in outcome was the
      added trunk stiffness and motion restriction by the iLSO. LEVEL OF EVIDENCE: 2.

PMID- 25054650
TI  - Impact of smoking on complication and pseudarthrosis rates after single- and 2
      level posterolateral fusion of the lumbar spine.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To study the impact of smoking
      status on postoperative complications and pseudarthrosis in adult patients
      undergoing posterolateral fusion (PLF) of the lumbar spine. SUMMARY OF BACKGROUND
      DATA: Results of studies analyzing the impact of smoking on complication and
      pseudarthrosis rates after spine surgery are conflicting. METHODS: A
      retrospective medical record review was performed to identify all adult patients
      who underwent single- and 2-level instrumented PLF without interbody devices for
      degenerative spine disease in a 21-year period at a single institution. Patients
      were divided into smokers and nonsmokers. The main outcome variables were
      development of at least one postoperative complication and development of
      pseudarthrosis. RESULTS: A total of 281 patients underwent single- or 2-level PLF
      in the 21-year period. Of these, 231 (82.21%) patients were nonsmokers and 50
      (17.9%) were smokers. For patients undergoing single-level PLF, complication
      rates in nonsmokers (3.57%) versus smokers (7.69%) were not significantly
      different (P = 0.353); pseudarthrosis in nonsmokers occurred in 9.82% of cases
      compared with 7.69% in the smokers group (P = 0.738). Nonsmokers undergoing 2
      level PLF had complication rates of 6.72%, compared with 4.17% in smokers (P =
      0.638), but pseudarthrosis rates were significantly higher in the smokers group
      than in the nonsmokers group (29.17% vs. 10.92%; P = 0.019). Patients were
      followed up for an average of 53.5 months. CONCLUSION: The findings in this study
      suggest that smoking has a significant impact on pseudarthrosis rates after 2
      level PLF of the lumbar spine, but not necessarily on single-level PLF. LEVEL OF
      EVIDENCE: 4.

PMID- 25054651
TI  - Biomechanical evaluation of the suture anchors used in open-door laminoplasty: a
      cadaveric study.
AB  - STUDY DESIGN: A cadaveric study. OBJECTIVE: To determine whether the use of
      suture anchors is warranted in cervical laminoplasty. SUMMARY OF BACKGROUND DATA:
      The use of suture anchors to stabilize elevated laminae has been popularized in
      laminoplasty. However, the validity of using suture anchors in laminoplasty has
      not been determined. METHODS: Six intact fresh frozen cadavers were used. Open
      door laminoplasty with a hinge on the cadaver's left side was performed on levels
      C3-C7. Elevated laminae were stabilized by suture anchors equipped with strain
      gauges, which were placed on C3, C5, and C7 left lateral masses. After surgery,
      the cervical spine was manually loaded passively, and the mechanical loads on
      each suture anchor during each motion were measured. Finally, the incision was
      opened again, and the failure loads of the suture anchors were also measured.
      RESULTS: After cervical loading, all elevated laminae were confirmed to be intact
      without dislodgement or failure of the suture anchors. The loads during left
      rotation and left bending were significantly higher than those during the
      respective motion to the right at all levels, except in rotation at C3. The loads
      on the C5 anchors in flexion and left rotation and on the C7 anchors in extension
      were relatively high. The maximum load obtained in the present study was 14.9 N,
      which was one order of magnitude lower than the mean failure load of the suture
      anchors (131.7 N). CONCLUSION: Biomechanical laterality was demonstrated,
      reflecting the asymmetrical nature of open-door laminoplasty. The maximum load on
      the suture anchors was much lower than the failure load and was consistent with
      the stability of the suture anchors encountered in clinical cases. This may
      support the validity of using suture anchors in laminoplasty, although the loads
      during active motion may be higher than our results. LEVEL OF EVIDENCE: N/A.

PMID- 25054652
TI  - Results of revision surgery after pedicle subtraction osteotomy for fixed
      sagittal imbalance with pseudarthrosis at the prior osteotomy site or elsewhere:
      minimum 5 years post-revision.
AB  - STUDY DESIGN: Retrospective review of pedicle subtraction osteotomy (PSO) cases.
      OBJECTIVE: To report our results, radiographic and clinical outcomes at a minimum
      5 years following revision surgery for pseudarthrosis after a PSO. SUMMARY OF
      BACKGROUND DATA: To our knowledge, there is no report on the results of revision
      surgery for pseudarthrosis after a PSO. METHODS: Eighteen consecutive patients
      with pseudarthrosis after PSO (16 females/2 males; average age at surgery, 49.8
      yr) treated with revision surgery at one institution were analyzed (average
      follow-up, 6.5 yr; range, 5-12 yr). Radiographic and clinical outcomes analysis
      was performed. RESULTS: Sagittal vertical axis (SVA) and lumbar lordosis (LL)
      improved significantly after revision surgery (SVA, P = 0.000; LL, P = 0.024) and
      were maintained until ultimate post-revision follow-up (SVA, P = 0.170; LL, P =
      0.729). Proximal junctional angle (P = 0.828), thoracic kyphosis (P = 0.828), and
      PSO angle (P = 0.717) achieved by the primary surgery were also maintained until
      ultimate post-revision. We increased the number of rods and/or changed them to
      6.35-mm diameter in all patients. There were significant improvements post
      revision in Oswestry Disability Index (45 vs. 37.9, P = 0.041) and Scoliosis
      Research Society pain subscale (2.6 vs. 3.1, P = 0.047) but not in Scoliosis
      Research Society total score or other subscales. Pelvic incidence greater than 60
      degrees  demonstrated a trend toward poorer Oswestry Disability Index and
      Scoliosis Research Society scores (P > 0.05), but there were no significant
      differences between SVA greater or less than 11 cm. CONCLUSION: Revision surgery
      for pseudarthrosis after PSO can provide acceptable radiographic and clinical
      outcomes at a minimum 5 years post-revision. Successful surgical outcomes may be
      achieved by using an increased number or size of implants and ample bone graft
      for complete fusion after revision surgery. LEVEL OF EVIDENCE: 4.

PMID- 25054653
TI  - Comprehensive analysis of three-dimensional activity cliffs formed by kinase
      inhibitors with different binding modes and cliff mapping of structural
      analogues.
AB  - Kinases are among the structurally most extensively characterized therapeutic
      targets. For many kinases, X-ray structures of inhibitor complexes are publicly
      available. We have identified all three-dimensional activity cliffs (3D-cliffs)
      formed by kinase inhibitors. More than 1300 X-ray structures of unique kinase
      inhibitor complexes and associated activity data were analyzed. On the basis of
      binding mode comparison and 3D similarity calculations, 105 3D-cliffs were
      detected for type I, type II, or type III inhibitors of 13 different kinases.
      Many of these activity cliffs revealed clear interaction differences between
      highly and weakly potent inhibitors. More than 200 structural analogues of 3D
      cliff compounds were identified whose structure-activity relationships (SARs) can
      be further explored in three dimensions on the basis of the corresponding 3D
      cliffs. In addition to SAR exploration, 3D-cliffs provide useful interaction
      hypotheses for structure-based design. The kinase inhibitor and activity cliff
      information is made freely available as a part of our study. 

PMID- 25054655
TI  - Biodegradable material for the absorption of organic compounds and nanoparticles.
AB  - Contaminants in water streams, in the form of oily/organic phases or
      nanoparticles, affect a large variety of activities, from laboratory practice up
      to environmental systems. To date, a large number of materials for the absorption
      and retention of these pollutants have been developed. Such materials, however,
      rarely conjugate high oil uptake, nanoparticle sequestration, biodegradability,
      and cost effectiveness simultaneously. In this work, we exploited the structural
      properties of dermal collagen networks and simple chemical manipulations to
      fabricate an original material that proved effective in separating water from
      organic and nanoparticulated contaminants. Our material is reusable,
      biodegradable, safe, and cost-effective and shows a high absorptive capacity of a
      large variety of organic compounds; it is also able to capture metallic
      nanoparticles. These features allow our material to effectively separate water
      from oily/nanoparticulate phases, thus making it an appropriate absorber for
      chemical processes and environmental protection. 

PMID- 25054656
TI  - Survival analysis, long-term outcomes, and percentage of recovery up to 8 years
      post-infection among the Houston West Nile virus cohort.
AB  - In 2012, we witnessed a resurgence of West Nile virus (WNV) in the United States,
      with the largest outbreak of human cases reported since 2003. WNV is now endemic
      and will continue to produce epidemics over time, therefore defining the long
      term consequences of WNV infection is critical. Over a period of eight years, we
      prospectively followed a cohort of 157 WNV-infected subjects in the Houston
      metropolitan area to observe recovery over time and define the long-term clinical
      outcomes. We used survival analysis techniques to determine percentage of
      recovery over time and the effects of demographic and co-morbid conditions on
      recovery. We found that 40% of study participants continued to experience
      symptoms related to their WNV infection up to 8 years later. Having a clinical
      presentation of encephalitis and being over age 50 were significantly associated
      with prolonged or poor recovery over time. Since the health and economic impact
      as a result of prolonged recovery, continued morbidity, and related disability is
      likely substantial in those infected with WNV, future research should be aimed at
      developing effective vaccines to prevent illness and novel therapeutics to
      minimize morbidity, mortality, and long-term complications from infection. 

PMID- 25054657
TI  - The prevalence of anxiety and depression in Chinese asthma patients.
AB  - It is well documented that the psychiatric disorders are common in Asthma
      patients in China while the studies on the relationship between asthma control
      and psychological disorder are comparatively rare. We therefore performed a cross
      sectional study on asthmatic outpatients in one Chinese tertiary center to
      investigate the correlation among asthma, anxiety and depression. Demographic
      data, anxiety and depression scores, the level of asthma control were collected
      in 261 patients. All patients were evaluated with Asthma Control Test (ACT), Self
      Rating Anxiety Scale (SAS) and Self-rating depression scale (SDS) questionnaires.
      A multivariate analysis was performed to investigate the relationship between
      asthma control and psychological disorder. The result showed that 31 asthma
      patients had anxiety symptom while thirty-five asthma patients had depression.
      One hundred and ninety-two asthma patients were well controlled and 69 patients
      were not. The study found a negative correlation between ACT and SAS(r = -0.231,
      p<0.001) as well as ACT and SDS(r = -0.23, p<0.001) and depression (OR: 12.295,
      95%CI: [5.374-28.128], p<0.001) were both independently associated with poor
      asthma control. We concluded that Asthma control is greatly affected by
      psychological disorder in Chinese patients.

PMID- 25054658
TI  - Reliability of clinician scoring of the functional movement screen to assess
      movement patterns.
AB  - Clinical Scenario: Injuries are inevitable in the physically active population.
      As a part of preventive medicine, health care professionals often seek clinical
      tools that can be used in real time to identify factors that may predispose
      individuals to these injuries. The Functional Movement Screen (FMS), a clinical
      tool consisting of 7 individual tasks, has been reported as useful in identifying
      individuals in various populations that may be susceptible to musculoskeletal
      injuries. If factors that may predispose physically active individuals to injury
      could be identified before participation, clinicians may be able to develop a
      training plan based on FMS scores, which could potentially decrease the
      likelihood of injury and overall time missed from physical activities. However,
      in order for a screening tool to be used clinically, it must demonstrate
      acceptable reliability. Focused Clinical Question: Are clinicians reliable at
      scoring the FMS, in real time, to assess movement patterns of physically active
      individuals? 

PMID- 25054659
TI  - Oncolytic virotherapy for gliomas: steps toward the future.

PMID- 25054660
TI  - Magnetic resonance spectroscopic imaging in the era of pseudoprogression and
      pseudoresponse in glioblastoma patient management.

PMID- 25054664
TI  - Bevacizumab for acute neurologic deterioration in patients with glioblastoma.
AB  - AIM: Glioblastoma causes neurologic dysfunction owing to the tumor's location and
      peritumoral edema. Bevacizumab improves symptoms and steroid dependence, and may
      rescue glioblastoma patients hospitalized for acute neurologic dysfunction,
      allowing them to return home for outpatient treatment. MATERIALS & METHODS: We
      carried out a retrospective review of glioblastoma patients with severe
      neurologic dysfunction who received bevacizumab as inpatients. RESULTS: Nine
      patients (median age: 51 years; median Karnofsky Performance Status [KPS]: 40%)
      received one dose of bevacizumab while admitted for neurologic deterioration.
      Seven patients were treated at recurrence, two at diagnosis. Six patients
      clinically improved and continued outpatient treatment, while five
      decreased/discontinued dexamethasone. CONCLUSION: Single bevacizumab treatment
      administered to naive hospitalized patients with glioblastoma improves function
      and quality of life through avoidance of prolonged hospitalization and
      rehabilitation admissions, and decreased dexamethasone administration.

PMID- 25054665
TI  - What is the most appropriate clinical target volume for glioblastoma?
AB  - Glioblastoma is one of the most common primary brain tumors in adults and the
      prognosis is very poor. The standard treatment is gross total resection and
      postoperative radiotherapy with concurrent and adjuvant chemotherapy with
      temozolomide. Given its propensity to spread to areas of brain parenchyma
      surrounding the gross tumor volume (GTV), a generous margin is typically created
      around the GTV. Peritumoral edema is frequently included in the GTV, especially
      in the USA. The margin of expansion from GTV to clinical target volume also
      varies widely among different institutions. There is a lack of consensus as to
      what constitutes the most appropriate clinical target volume for glioblastoma.

PMID- 25054666
TI  - Role of stereotactic body radiotherapy in spinal metastasis and subsequent
      fracture risk: identifying and treating the at-risk patient.
AB  - The treatment of spinal metastasis has considerably improved with the advent of
      stereotactic body radiotherapy. Technological advances have enabled the precise
      delivery of high-dose radiation that may supplant surgery and standard
      fractionation postoperative radiation as a treatment for spinal metastasis
      without cord compression. Unfortunately, the higher biologically equivalent doses
      conferred by stereotactic body radiotherapy can also result in radiation
      toxicity, notably myelitis and vertebral body fracture. These are toxicities that
      the radiation oncologist must be able to anticipate, mitigate and manage.
      Although myelitis can be prevented largely by instituting dose constraints, it is
      less clear what the fracture risk of a structurally compromised vertebra is, and
      what should be done in terms of stabilization and dosimetry to mitigate this
      risk. This review answers these questions by defining the appropriate patient for
      stereotactic body radiotherapy, and what dose, fractionation and spinal
      stabilization should be used for potentially unstable spines.

PMID- 25054667
TI  - Strategies to accelerate diagnosis of primary brain tumors at the primary
      secondary care interface in children and adults.
AB  - This article presents a shared view from practitioners with special interests in
      diagnosing and managing primary brain tumors in both primary and secondary care,
      in adult and pediatric disciplines; it examines the complexity of identifying
      whether it would be of benefit and feasible to try to identify those with brain
      tumors earlier, how this could be achieved and what evidence exists to justify
      such an approach. The experience of the HeadSmart Campaign in childhood brain
      tumor, using awareness as a method for driving service change, is used to
      illustrate how diagnostic practice can be changed across the primary and
      secondary care interface. This article highlights the importance of focusing upon
      the needs of patients with primary brain tumors as they represent a significant
      set of life-threatening and disabling diseases with significant implications for
      cancer and palliative services.

PMID- 25054670
TI  - Women living with HIV and healthcare reform.

PMID- 25054669
TI  - Evidence for distinct electron transfer processes in terminal oxidases from
      different origin by means of protein film voltammetry.
AB  - Cytochrome aa3 from Paracoccus denitrificans and cytochrome ba3 from Thermus
      thermophilus, two distinct members of the heme-copper oxidase superfamily, were
      immobilized on electrodes modified with gold nanoparticles. This procedure
      allowed us to achieve direct electron transfer between the enzyme and the gold
      nanoparticles and to obtain evidence for different electrocatalytic properties of
      the two enzymes. The pH dependence and thermostability reveal that the enzymes
      are highly adapted to their native environments. These results suggest that
      evolution resulted in different solutions to the common problem of electron
      transfer to oxygen. 

PMID- 25054671
TI  - Short- and long-term outcome in elderly patients after out-of-hospital cardiac
      arrest: a cohort study.
AB  - OBJECTIVE: Determinants of outcome and long-term survival are unknown in elderly
      patients successfully resuscitated after out-of-hospital cardiac arrest. Our aim
      was to identify factors associated with short- and long-term neurologic outcome
      in such patients. DESIGN: Retrospective cohort study. SETTING: Tertiary hospital
      in Paris, France. PATIENTS: Patients aged over 75 admitted in our ICU after an
      out-of-hospital cardiac arrest between 2000 and 2009. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Two hundred twenty-five patients were included in
      the study. Fifty-seven patients (25.3%) had a good neurologic outcome at ICU
      discharge (Cerebral Performance Category 1-2). By multivariate logistic
      regression analysis, factors associated with good short-term outcome were time
      from collapse to cardiopulmonary resuscitation less than or equal to 3 minutes
      (odds ratio = 4.06; 95% CI, 1.49-11.09, p = 0.006) and blood lactate level less
      than or equal to 5.1 mmol/L (odds ratio = 3.30; 95% CI, 1.05-10.39, p = 0.04),
      but age less than or equal to 79.5 years and use of induced hypothermia were not.
      Long-term survivors were assessed for cognitive and functional status (using
      Cerebral Performance Category and Overall Performance Category scales), and their
      survival was compared with a large community-based cohort of participants over 75
      years. The 1-year survival of ICU survivors (mean follow-up, 28.4 mo) was 69.3%
      (95% CI, 55.8-79.5) as compared with 95.3% (95% CI, 93.3-97.3) in the control
      community-based cohort (p< 0.001), resulting in a standardized mortality ratio of
      3.49 (95% CI, 2.42-4.85). By multivariate Cox proportional hazard model, factors
      associated with long-term survival were initial shockable rhythm (hazard ratio =
      1.41; 95% CI, 1.01-1.96; p = 0.04), epinephrine cumulate dose less than or equal
      to 3 mg (hazard ratio = 1.48; 95% CI, 1.06-2.08; p = 0.02), and blood lactate
      level less than or equal to 5.1 mmol/L (hazard ratio = 2.11; 95% CI, 1.5-2.96; p
      < 0.001). When available at end of follow-up, 91% and 74% of the patients were
      classified Cerebral Performance Category 1 and Overall Performance Category 1,
      respectively. CONCLUSIONS: Neurologic outcome in successfully resuscitated
      elderly patients depends on cardiac arrest characteristics rather than age. Short
      term survival is 25% with acceptable long-term outcome among survivors.

PMID- 25054672
TI  - Long-term (10-year) mortality of younger previously healthy patients with severe
      sepsis/septic shock is worse than that of patients with nonseptic critical
      illness and of the general population.
AB  - OBJECTIVES: Long-term (1- to 10-year) outcomes after severe sepsis in previously
      healthy persons are unknown. We aimed to determine the 1- to 10-year mortality
      rates of previously healthy patients with severe sepsis and compare these to
      mortality rates of patients with nonseptic critical illness and the general
      population. DESIGN: A prospective cohort study of 2,289 patients from one mixed
      medical-surgical ICU and one cardiovascular surgery ICU. Age- and gender
      comparable general British Columbia population was used as comparison. Patients
      were followed from the date of admission to the ICU to January 31, 2013.
      Provincial vital statistics were used to determine the patients' date of death.
      For the general population comparison, expected survival was obtained from life
      tables of the population of British Columbia, Canada. SETTING: A quaternary-level
      provincial referral hospital in Vancouver, British Columbia, Canada. PATIENTS:
      Two thousand two hundred eighty-nine patients from one mixed medical-surgical ICU
      and one cardiovascular surgery ICU. Age- and gender-comparable general British
      Columbia population was used for comparison. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Patients with severe sepsis without comorbidities had higher
      mortality from 1 to 10 years than general British Columbia population (p < 0.01).
      Younger patients with severe sepsis (< 60 yr) had the worst 1- to 5-year and 5-
      to 10-year mortality (hazard ratio [95% CI], 17.8 [13.4-24.8] and 6.0 [4-9])
      compared with the general population. Patients with severe sepsis had
      significantly poorer 1- to 10-year mortality rates (30.5%) compared with patients
      with nonseptic critical illness (22.1%) and patients who have undergone
      cardiovascular surgery (15.9%). Patients with sepsis had higher mortality rates
      from 1-5 years and 5-10 years than the general British Columbia population
      (hazard ratio [95% CI], 4.5 [2.2-9.1] and 2.2 [0.9-14.7]). CONCLUSIONS:
      Previously healthy patients suffering an episode of severe sepsis have increased
      long-term mortality compared with patients with nonseptic critical illness and a
      general population.

PMID- 25054673
TI  - Error in intensive care: psychological repercussions and defense mechanisms among
      health professionals.
AB  - OBJECTIVE: To identify the psychological repercussions of an error on
      professionals in intensive care and to understand their evolution. To identify
      the psychological defense mechanisms used by professionals to cope with error.
      DESIGN: Qualitative study with clinical interviews. We transcribed recordings and
      analysed the data using an interpretative phenomenological analysis. SETTING: Two
      ICUs in the teaching hospitals of Besancon and Dijon (France). SUBJECTS: Fourteen
      professionals in intensive care (20 physicians and 20 nurses). INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: We conducted 40 individual semistructured
      interviews. The participants were invited to speak about the experience of error
      in ICU. The interviews were transcribed and analyzed thematically by three
      experts. In the month following the error, the professionals described feelings
      of guilt (53.8%) and shame (42.5%). These feelings were associated with anxiety
      states with rumination (37.5%) and fear for the patient (23%); a loss of
      confidence (32.5%); an inability to verbalize one's error (22.5%); questioning
      oneself at a professional level (20%); and anger toward the team (15%). In the
      long term, the error remains fixed in memory for many of the subjects (80%); on
      one hand, for 72.5%, it was associated with an increase in vigilance and
      verifications in their professional practice, and on the other hand, for three
      professionals, it was associated with a loss of confidence. Finally, three
      professionals felt guilt which still persisted at the time of the interview. We
      also observed different defense mechanisms implemented by the professional to
      fight against the emotional load inherent in the error: verbalization (70%),
      developing skills and knowledge (43%), rejecting responsibility (32.5%), and
      avoidance (23%). We also observed a minimization (60%) of the error during the
      interviews. CONCLUSIONS: It is important to take into account the psychological
      experience of error and the defense mechanisms developed following an error
      because they appear to determine the professional's capacity to acknowledge and
      disclose his/her error and to learn from it.

PMID- 25054674
TI  - Global prospective epidemiologic and surveillance study of ventilator-associated
      pneumonia due to Pseudomonas aeruginosa.
AB  - OBJECTIVE: To estimate the prevalence of ventilator-associated pneumonia caused
      by Pseudomonas aeruginosa in patients at risk for ventilator-associated pneumonia
      and to describe risk factors for P. aeruginosa ventilator-associated pneumonia.
      DESIGN: Prospective, observational study. SETTING: ICUs at 56 sites in 11
      countries across four regions: the United States (n = 502 patients), Europe (n =
      495), Latin America (n = 500), and Asia Pacific (n = 376). PATIENTS: Adults
      intubated and mechanically ventilated for 48 hours to 7 days, inclusive.
      INTERVENTIONS: None (local standard of care). MEASUREMENTS AND MAIN RESULTS:
      Ventilator-associated pneumonia prevalence as defined by local investigators were
      15.6% (293/1,873) globally, 13.5% in the United States, 19.4% in Europe, 13.8% in
      Latin America, and 16.0% in Asia Pacific (p = 0.04). Corresponding P. aeruginosa
      ventilator-associated pneumonia prevalences were 4.1%, 3.4%, 4.8%, 4.6%, and 3.2%
      (p = 0.49). Of 50 patients with P. aeruginosa ventilator-associated pneumonia who
      underwent surveillance testing, 19 (38%) had prior P. aeruginosa colonization and
      31 (62%) did not (odds ratio, 7.99; 95% CI, 4.31-14.71). Of predefined risk
      factors for multidrug resistance (hereafter, risk factors), the most frequent in
      all patients were antimicrobial therapy within 90 days (51.9% of enrolled
      patients) and current hospitalization of more than or equal to 5 days (45.3%).
      None of these risk factors were significantly associated with P. aeruginosa
      ventilator-associated pneumonia by multivariate logistic regression. Risk factors
      associated with prior P. aeruginosa colonization were antimicrobial therapy
      within 90 days (odds ratio, 0.46; 95% CI, 0.29-0.73) and high proportion of
      antibiotic resistance in the community or hospital unit (odds ratio, 1.79; 95%
      CI, 1.14-2.82). CONCLUSIONS: Our findings suggest that ventilator-associated
      pneumonia remains a common ICU infection and that P. aeruginosa is one of the
      most common causative pathogens. The odds of developing P. aeruginosa ventilator
      associated pneumonia were eight times higher in patients with prior P. aeruginosa
      colonization than in uncolonized patients, which in turn was associated with
      local resistance.

PMID- 25054675
TI  - Economic evaluation of decompressive craniectomy versus barbiturate coma for
      refractory intracranial hypertension following traumatic brain injury.
AB  - OBJECTIVES: Decompressive craniectomy and barbiturate coma are often used as
      second-tier strategies when intracranial hypertension following severe traumatic
      brain injury is refractory to first-line treatments. Uncertainty surrounds the
      decision to choose either treatment option. We investigated which strategy is
      more economically attractive in this context. DESIGN: We performed a cost-utility
      analysis. A Markov Monte Carlo microsimulation model with a life-long time
      horizon was created to compare quality-adjusted survival and cost of the two
      treatment strategies, from the perspective of healthcare payer. Model parameters
      were estimated from the literature. Two-dimensional simulation was used to
      incorporate parameter uncertainty into the model. Value of information analysis
      was conducted to identify major drivers of decision uncertainty and focus future
      research. SETTING: Trauma centers in the United States. SUBJECTS: Base case was a
      population of patients (mean age = 25 yr) who developed refractory intracranial
      hypertension following traumatic brain injury. INTERVENTIONS: We compared two
      treatment strategies: decompressive craniectomy and barbiturate coma.
      MEASUREMENTS AND MAIN RESULTS: Decompressive craniectomy was associated with an
      average gain of 1.5 quality-adjusted life years relative to barbiturate coma,
      with an incremental cost-effectiveness ratio of $9,565/quality-adjusted life year
      gained. Decompressive craniectomy resulted in a greater quality-adjusted life
      expectancy 86% of the time and was more cost-effective than barbiturate coma in
      78% of cases if our willingness-to-pay threshold is $50,000/quality-adjusted life
      year and 82% of cases at a threshold of $100,000/quality-adjusted life year. At
      older age, decompressive craniectomy continued to increase survival but at higher
      cost (incremental cost-effectiveness ratio = $197,906/quality-adjusted life year
      at mean age = 85 yr). CONCLUSIONS: Based on available evidence, decompressive
      craniectomy for the treatment of refractory intracranial hypertension following
      traumatic brain injury provides better value in terms of costs and health gains
      than barbiturate coma. However, decompressive craniectomy might be less
      economically attractive for older patients. Further research, particularly on
      natural history of severe traumatic brain injury patients, is needed to make more
      informed treatment decisions.

PMID- 25054677
TI  - Infant body composition in the PEA POD(r) era: what have we learned and where do
      we go from here?
AB  - The availability of clinically feasible infant body composition assessment can
      inform current questions regarding the developmental origins of chronic disease.
      A strategic approach will facilitate more rapid advancement in knowledge. The
      objective of this study was to summarize published evidence and ongoing research
      activity in infant body composition using the PEA POD(r) infant body composition
      system. All published studies using the PEA POD(r) were identified and grouped
      according to study population and question. All centers with PEA POD(r) units
      were invited to participate in an online survey regarding past, current and
      future PEA POD(r) use, and results were analyzed using descriptive statistics.
      The resulting information was used to identify gaps or limitations in existing
      knowledge, thus highlighting potential research priorities. Twenty-seven
      published articles were identified and grouped into six research themes. Although
      the number of infants studied is significant in some areas, interpretation of
      data is limited by methodological differences. Survey responses were received
      from 16 of ~60 centers. Research themes echoed those identified from the
      published literature. Controlling for or reporting potential confounding
      variables is essential for understanding infant body composition data.
      Measurement of health outcome variables would be helpful in identifying
      associations. 

PMID- 25054676
TI  - Placental transport in response to altered maternal nutrition.
AB  - The mechanisms linking maternal nutrition to fetal growth and programming of
      adult disease remain to be fully established. We review data on changes in
      placental transport in response to altered maternal nutrition, including
      compromized utero-placental blood flow. In human intrauterine growth restriction
      and in most animal models involving maternal undernutrition or restricted
      placental blood flow, the activity of placental transporters, in particular for
      amino acids, is decreased in late pregnancy. The effect of maternal overnutrition
      on placental transport remains largely unexplored. However, some, but not all,
      studies in women with diabetes giving birth to large babies indicate an
      upregulation of placental transporters for amino acids, glucose and fatty acids.
      These data support the concept that the placenta responds to maternal nutritional
      cues by altering placental function to match fetal growth to the ability of the
      maternal supply line to allocate resources to the fetus. On the other hand, some
      findings in humans and mice suggest that placental transporters are regulated in
      response to fetal demand signals. These observations are consistent with the idea
      that fetal signals regulate placental function to compensate for changes in
      nutrient availability. We propose that the placenta integrates maternal and fetal
      nutritional cues with information from intrinsic nutrient sensors. Together,
      these signals regulate placental growth and nutrient transport to balance fetal
      demand with the ability of the mother to support pregnancy. Thus, the placenta
      plays a critical role in modulating maternal-fetal resource allocation, thereby
      affecting fetal growth and the long-term health of the offspring. 

PMID- 25054679
TI  - Placental expression of the obesity-associated gene FTO is reduced by fetal
      growth restriction but not by macrosomia in rats and humans.
AB  - Genetic variants in the FTO (fat mass- and obesity-associated) gene have the
      highest association of all obesity-associated genes. Its placental expression was
      shown to relate to birth weight, suggesting that it may participate in the
      control of fetal weight gain. To gain more insight into the implication of FTO in
      fetal growth, we measured its placental expression in samples including extremes
      of abnormal fetal growth, such as after intrauterine growth restriction (IUGR) or
      macrosomia in both rats and humans. In rats, fetal growth was modulated by
      maternal nutritional modifications. In humans, placental villi were collected
      from pathological pregnancies (i.e. with IUGR or fetal macrosomia). Placental FTO
      mRNA expression was reduced by IUGR but was not significantly affected by
      macrosomia in either rats or humans. Our data suggest that placental FTO may
      participate in interactions between the in utero environment and the control of
      fetal growth under IUGR conditions by modulating epigenetic processes. 

PMID- 25054678
TI  - Prematurity and programming: contribution of neonatal Intensive Care Unit
      interventions.
AB  - Contemporary clinical practice for the care of the prematurely born babies has
      markedly improved their rates of survival so that most of these babies are
      expected to grow up to live a healthy functional life. Since the clinical follow
      up is of short duration (years), only limited data are available to relate non
      communicable diseases in adult life to events and interventions in the neonatal
      period. The major events that could have a programming effect include: (1)
      intrauterine growth restriction; (2) interruption of pregnancy with change in
      redox and reactive oxygen species (ROS) injury; (3) nutritional and
      pharmacological protocols for clinical care; and (4) nutritional care in the
      first 2 years resulting in accelerated weight gain. The available data are
      discussed in the context of perturbations in one carbon (methyl transfer)
      metabolism and its possible programming effects. Although direct evidence for
      genomic methylation is not available, clinical and experimental data on impact of
      redox and ROS, of low protein intake, excess methionine load and vitamin A, on
      methyl transfers are reviewed. The consequences of antenatal and postnatal
      administration of glucocorticoids are presented. Analysis of the correlates of
      insulin sensitivity at older age, suggests that premature birth is the major
      contributor, and is compounded by gain in weight during infancy. We speculate
      that premature interruption of pregnancy and neonatal interventions by affecting
      one carbon metabolism may cause programming effects on the immature baby. These
      can be additive to the effects of intrauterine environment (growth restriction)
      and are compounded by accelerated growth in early infancy. 

PMID- 25054680
TI  - Birth weight predicts both proteinuria and overweight/obesity in a rural
      population of Aboriginal and non-Aboriginal Canadians.
AB  - The risk for many chronic diseases appears to be mediated in part by birth
      weight. Among Aboriginal Canadians, the prevalence of end-stage renal disease and
      cardiovascular disease risk is disproportionately high, largely because of
      elevated diabetes prevalence. The relationships between birth weight (and other
      potential risk factors) and diabetes, hypertension, proteinuria and
      overweight/obesity were explored in 1439 rural Albertans (Canada), of whom 67.3%
      were Aboriginal. At voluntary outreach screening programs, demographic and
      clinical data were measured and recalled birth weights recorded. Statistical
      modeling using logistic regression was used to evaluate the relationships. In the
      final adjusted models, associations remained for low birth weight and proteinuria
      [odds ratio (OR) 2.36; 95% CI 1.24-4.49], as well as for high birth weight and
      overweight/obesity (OR 1.58; 95% CI 1.00-2.53). These findings emphasize the need
      to strive for healthy pregnancies, with appropriate weight gains in these and
      other disadvantaged populations around the world. 

PMID- 25054681
TI  - Effects of glucocorticoid treatment given in early or late gestation on growth
      and development in sheep.
AB  - Antenatal corticosteroids are used to augment fetal lung maturity in human
      pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal
      hyperplasia of the fetus in early pregnancy. We previously reported effects of
      synthetic corticosteroids given to sheep in early or late gestation on pregnancy
      length and fetal cortisol levels and glucocorticoids alter plasma insulin-like
      growth factor (IGF) and insulin-like growth factor binding protein (IGFBP)
      concentrations in late pregnancy and reduce fetal weight. The effects of
      administering DEX in early pregnancy on fetal organ weights and betamethasone
      (BET) given in late gestation on weights of fetal brain regions or organ
      development have not been reported. We hypothesized that BET or DEX
      administration at either stage of pregnancy would have deleterious effects on
      fetal development and associated hormones. In early pregnancy, DEX was
      administered as four injections at 12-hourly intervals over 48 h commencing at 40
      42 days of gestation (dG). There was no consistent effect on fetal weight, or
      individual fetal organ weights, except in females at 7 months postnatal age. When
      BET was administered at 104, 111 and 118 dG, the previously reported reduction in
      total fetal weight was associated with significant reductions in weights of fetal
      brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and
      triiodothyronine were also reduced at different times in fetal and postnatal
      life. We conclude that at the amounts given, the sheep fetus is sensitive to
      maternal administration of synthetic glucocorticoid in late gestation, with
      effects on growth and metabolic hormones that may persist into postnatal life. 

PMID- 25054682
TI  - Polymorphisms in genes within the IGF-axis influence antenatal and postnatal
      growth.
AB  - Two pregnancy cohorts were used to investigate the association between single
      nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor
      (IGF)-axis and antenatal and postnatal growth from birth to adolescence.
      Longitudinal analyses were conducted in the Raine pregnancy cohort (n = 1162)
      using repeated measures of fetal head circumference (HC), abdominal circumference
      (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of
      postnatal height and weight (1-17 years). Replications of significant
      associations up to birth were undertaken in the Generation R Study (n = 2642). Of
      the SNPs within the IGF-axis genes, 40% (n = 58) were associated with measures of
      antenatal growth (P ? 0.05). The majority of these SNPs were in receptors; IGF-1R
      (23%; n = 34) and IGF-2R (13%; n = 9). Fifteen SNPs were associated with
      antenatal growth (either AC or HC or FL) in Raine (P ? 0.005): five of which
      remained significant after adjusting for multiple testing. Four of these
      replicated in Generation R. Associations were identified between 38% (n = 55) of
      the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n = 31) and 9%
      in IGF-2R (n = 13). Twenty-six SNPs were significantly associated with both
      antenatal and postnatal growth; 17 with discordant effects and nine with
      concordant effects. Genetic variants in the IGF-axis appear to play a significant
      role in antenatal and postnatal growth. Further replication and new analytic
      methods are required in order to better understand this key metabolic pathway
      integrating biologic knowledge about the interaction between IGF-axis components.

PMID- 25054683
TI  - Early origins of longevity: prenatal exposures to food shortage among early Utah
      pioneers.
AB  - Undernutrition during critical or sensitive prenatal periods may 'program' the
      fetus for increased chronic disease and mortality in later life. Using birth
      cohorts that were or were not exposed to severe food shortage in Utah in the mid
      19th century, this study examines how in utero exposure to undernutrition is
      associated with mortality after age 50. The Utah Population Database is used to
      identify 1392 prenatally exposed individuals and 29,022 individuals from
      subsequent, unexposed birth cohorts. Gompertz hazards with parametric frailty
      show that males born between April and June of the famine period (and hence
      exposed during critical periods in utero during the winter months) have higher
      mortality risks compared with post-famine cohorts. Alternative Cox non
      proportional hazard models suggest that females born during the same period have
      higher initial mortality risks (starting at age 50) that decline over time
      creating a mortality crossover with unexposed women at approximately age 70, a
      result not found for men. An ancillary sibling analysis that uses shared frailty
      survival models to compare individuals with prenatal exposure to undernutrition
      to their younger (post-famine) same-sex siblings finds no significant differences
      in adult mortality for males but the pattern for females support the findings
      from the previous analysis. Although findings are sensitive to model choice, this
      study presents evidence that is consistent with an association between
      undernutrition in utero and adult mortality, shows that effects may be sensitive
      to the duration and gestational period of exposure, and illustrates the
      differential exposure effects between genders. 

PMID- 25054685
TI  - Street drug use during pregnancy: potential programming effects on preschool
      wheeze.
AB  - Street drug use during pregnancy is detrimental to fetal development. Although
      the prevalence of wheeze is high in offspring of substance-abusing mothers,
      nothing is known about the role of street drug use during pregnancy in its
      development. We investigated the impact of maternal street drug use and distress
      during pregnancy on the development of wheeze and allergy in preschool children.
      Questionnaire data were accessed from the Community Perinatal Care trial of 791
      mother-child pairs in Calgary, Alberta. Using logistic regression, the
      association between maternal substance use and distress during pregnancy, and
      wheeze and allergy at age 3 years was determined in boys and girls. After
      adjusting for alcohol use during pregnancy, pre- and postnatal tobacco use,
      preterm birth, duration of exclusive breastfeeding, daycare attendance and
      maternal socioeconomic status, maternal street drug use during pregnancy [odds
      ratio (OR): 5.02, 95% confidence interval (CI): 1.30-19.4] and severe maternal
      distress during pregnancy (OR: 5.79, 95% CI: 1.25-26.8) were associated with
      wheeze in girls. In boys, an independent association was found between severe
      distress during pregnancy (OR: 3.85, 95% CI: 1.11-13.3) and allergies, but there
      was no association with maternal street drug use. In conclusion, we found an
      association between maternal street drug use and wheeze in preschool girls that
      could not be accounted for by maternal distress, smoking or alcohol use during
      pregnancy. Prenatal programming effects of street drugs may explain this
      association. 

PMID- 25054684
TI  - Exposures in early life: associations with DNA promoter methylation in breast
      tumors.
AB  - There is evidence that epigenetic changes occur early in breast carcinogenesis.
      We hypothesized that early-life exposures associated with breast cancer would be
      associated with epigenetic alterations in breast tumors. In particular, we
      examined DNA methylation patterns in breast tumors in association with several
      early-life exposures in a population-based case-control study. Promoter
      methylation of E-cadherin, p16 and RAR-beta2 genes was assessed in archived tumor
      blocks from 803 cases with real-time methylation-specific PCR. Unconditional
      logistic regression was used for case-case comparisons of those with and without
      promoter methylation. We found no differences in the prevalence of DNA
      methylation of the individual genes by age at menarche, age at first live birth
      and weight at age 20. In case-case comparisons of premenopausal breast cancer,
      lower birth weight was associated with increased likelihood of E-cadherin
      promoter methylation (OR = 2.79, 95% CI, 1.15-6.82, for ?2.5 v. 2.6-2.9 kg);
      higher adult height with RAR-beta2 methylation (OR = 3.34, 95% CI, 1.19-9.39, for
      ?1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75,
      95% CI, 1.14-6.62). Among postmenopausal breast cancers, birth order was
      associated with increased likelihood of p16 promoter methylation. Being other
      than first in the birth order was inversely associated with likelihood of ?1 of
      the three genes being methylated for premenopausal breast cancers, but positively
      associated with methylation in postmenopausal women. These results suggest that
      there may be alterations in methylation associated with early-life exposures that
      persist into adulthood and affect breast cancer risk. 

PMID- 25054686
TI  - Non-antibiotic agent ginsenoside 20(S)-Rh2 enhanced the antibacterial effects of
      ciprofloxacin in vitro and in vivo as a potential NorA inhibitor.
AB  - The aim of this study is to explore the potential enhancing effect of ginsenoside
      20(S)-Rh2 (Rh2) towards ciprofloxacin (CIP) against Staphylococcus aureus (S.
      aureus) infection in vitro and in vivo, and analyze the possible mechanisms
      through NorA inhibition from a target cellular pharmacokinetic view. In
      combination with non-toxic dosage of Rh2, the susceptibilities of S. aureus
      strains to CIP were significantly augmented, and the antibacterial kinetics of
      CIP in the S. aureus strains were markedly promoted. This enhancing effect of Rh2
      towards CIP was also observed in S. aureus infected peritonitis mice, with
      elevated survival rate and reduced bacteria counts in blood. However, Rh2 did not
      influence the plasma concentrations of CIP. Further analysis indicated that Rh2
      significantly promoted the accumulations of CIP in S. aureus, and inhibited the
      NorA mediated efflux of pyronin Y. The expressions of NorA gene on S. aureus were
      positively correlated with the enhancing effect of Rh2 with CIP. This is the
      first report of the enhancing effect of Rh2 with CIP for S. aureus infection in
      vitro and in vivo, of which it is probably that Rh2 inhibited NorA-mediated
      efflux and promoted the accumulation of CIP in the bacteria. 

PMID- 25054687
TI  - Photoluminescent graphene nanoparticles for cancer phototherapy and imaging.
AB  - Graphene-based nanomaterials are of great interest in a wide range of
      applications in electronics, the environment, and energy as well as in biomedical
      and bioengineering. Their unique properties make them generally applicable as
      prognostic, diagnostic, and therapeutic agents in cancer. In this work, we
      focused on photodynamic and photothermal therapeutic properties of our previously
      synthesized carboxylated photoluminescent graphene nanodots (cGdots). The cGdots
      are ~5 nm in diameter and excited at 655 nm. Our findings reveal that, upon laser
      irradiation by near-infrared (wavelength 670 nm) sensitizer, electrons of the
      cGdots starts to vibrate and form electron clouds, thereby generating sufficient
      heat (>50  degrees C) to kill the cancer cells by thermal ablation. The
      generation of singlet oxygen also occurs due to irradiation, thus acting
      similarly to pheophorbide-A, a well-known photodynamic therapeutic agent. The
      cGdots kills MDA-MB231 cancer cells (more than 70%) through both photodynamic and
      photothermal effects. The cGdots were equally effective in the in vivo model of
      MDA-MB231 xenografted tumor-bearing mice also as observed for 21 days. The cGdot
      was intravenously injected, and the tumor was irradiated by laser, resulting in
      final volume of tumor was ~70% smaller than that of saline-treated tumor. It
      indicates that the growth rate of cGdot-treated tumor was slower compared to
      saline-treated tumor. The synthesized cGdots could enable visualization of tumor
      tissue in mice, thereby illustrating their use as optical imaging agents for
      detecting cancer noninvasively in deep tissue/organ. Collectively, our findings
      reveal that multimodal cGdots can be used for phototherapy, through photothermal
      or photodynamic effects, and for noninvasive optical imaging of deep tissues and
      tumors simultaneously. 

PMID- 25054688
TI  - Flavonol content, oil%, and fatty acid composition variability in seeds of
      Teramnus labialis and T. uncinatus accessions with nutraceutical potential.
AB  - Teramnus labialis and T. uncinatus are both underutilized legume species.
      Teramnus labialis is used as food in India while T. uncinatus has potential use
      in pasture mixes. Photoperiod-sensitive Teramnus accessions were grown in the
      greenhouse from 2010 to 2011 and evaluated for flavonol content, oil%, and fatty
      acid compositions. Significant variations for seed numbers produced, flavonol
      content, oil%, and fatty acid compositions were detected. Seed numbers ranged
      from 16 to 3,792 in both species. Teramnus accessions produced more quercetin
      (ranging from 0.615 to 2.228 mg/g) in their seeds than the other flavonols.
      However kaempferol and isorhamnetin content ranged from 0 to 0.066 and 0 to 0.086
      mg/g (dry seed weight basis), respectively among all accessions. Oil% ranged from
      2.65 to 5.64% and more oleic, linoleic, and linolenic acids ranging from 6.69 to
      25.97, 31.82 to 41.44, and 17.7 to 32.66%, respectively, were produced among all
      Teramnus accessions. The seeds from all Teramnus accessions also produced the
      least saturated fatty acid compositions (ranging from 0.08 to 15.36%). Several
      significant correlations were also detected for these traits among the
      accessions. Quercetin showed highly significant positive correlations with
      kaempferol (r = 0.59, p < .0001), oil% (r = 0.58, p < .0001), and oleic acid (r =
      0.31, p < .001). Quercetin also showed a significant negative correlation with
      linoleic acid (r = -0.49, p < .0001). These correlations are important because
      useful breeding procedures could be conducted on improving flavonol, oil%, and
      fatty acid compositions in Teramnus labialis and T. uncinatus accessions.

PMID- 25054689
TI  - Design of ratiometric emission probe with visible light excitation for
      determination of Ca2+ in living cells.
AB  - An organic salt as a fluorescent probe based on intramolecular charge transfer
      for Ca(2+) determination is developed. Ca(2+) can be detected by ratiometric
      emission at 490 and 594 nm with an excitation wavelength of 405 nm. This probe is
      highly selective for Ca(2+) over other divalent metal cations and displays a
      large Stokes shift of 189 nm that can avoid interference of the excitation light
      beam and autofluorescence of biological samples. The dissociation constant for
      Ca(2+) is 2.25 +/- 0.47 MUM and pertinent to Ca(2+) detection in cellular resting
      and dynamic states. The probe demonstrates its application in monitoring Ca(2+)
      in living cells under confocal microscopic imaging. 

PMID- 25054690
TI  - Disparities in adverse childhood experiences among individuals with a history of
      military service.
AB  - IMPORTANCE: Adverse childhood experiences (ACEs) are associated with several
      adulthood health problems, such as self-directed violence. For some individuals,
      enlistment in the military may be an instrumental act to escape adverse household
      environments; however, to our knowledge prevalence of ACEs among persons with a
      history of military service has not been documented in the United States using
      population-based data. OBJECTIVE: To compare the prevalence of ACEs among
      individuals with and without a history of military service. DESIGN, SETTING, AND
      PARTICIPANTS: Data are from the 2010 Behavioral Risk Factor Surveillance System.
      Computer-assisted telephone interviews were conducted with population-based
      samples of noninstitutionalized US adults from January 1 through December 31,
      2010. Analyses were limited to respondents who received the ACE module (n =
      60,598). Participants were categorized by history of military service and whether
      a respondent was 18 years of age in 1973. MAIN OUTCOMES AND MEASURES: History of
      military service was defined by active duty service, veteran status, or training
      for the Reserves or National Guard. The ACE inventory assessed 11 negative
      experiences before the age of 18 years. Weighted chi2 tests and multiple logistic
      regression analyses were used to examine differences in ACEs by history of
      military service, era of service, and sex. RESULTS: Those with military
      experience had greater odds of any difference in prevalence of ACEs. In the all
      volunteer era, men with military service had a higher prevalence of ACEs in all
      11 categories than men without military service. Notably, in the all-volunteer
      era, men with military service had twice the odds of reporting forced sex before
      the age of 18 years (odds ratio, 2.19; 95% CI, 1.34-3.57) compared with men
      without military service. In the draft era, the only difference among men was
      household drug use, in which men with a history of military service had a
      significantly lower prevalence than men without a history of military service
      (2.1% vs. 3.3%; P = .003). Fewer differences were observed among women in the all
      volunteer and draft eras. CONCLUSIONS AND RELEVANCE: Differences in ACEs by era
      and sex lend preliminary support that enlistment may serve as an escape from
      adversity for some individuals, at least among men. Further research is needed to
      understand how best to support service members and veterans who may have
      experienced ACEs.

PMID- 25054691
TI  - Reactivity and aromaticity of nucleobases are sensitive toward external electric
      field.
AB  - Reactivity and aromaticity of DNA and RNA bases toward an external electric field
      are analyzed using density functional theory (DFT) and density functional
      reactivity theory (DFRT). Reactivity of the nucleobases is measured in terms of
      the DFT-based reactivity descriptor, such as energy of the HOMO, global hardness,
      electrophilicity, etc. and is observed to be sensitive toward the strength as
      well as direction of the applied external electric field. In addition, the
      reactivity pattern follows the maximum hardness and minimum electrophilicity
      principles. Further, aromaticity of the species is observed to be effected by the
      presence of an external electric field. 

PMID- 25054692
TI  - Nursing in search of quality and resolution of Primary Care Health.

PMID- 25054693
TI  - [Instrument for evaluating the actions of leprosy control in Primary Care].
AB  - The study aimed to construct and validate an instrument to assess the leprosy
      actions control in primary care from the perspective of community health agents
      (CHA). This is a methodological study to validate instruments, based on the
      Classical Test Theory. The instrument was administered to 380 CHA of three
      municipalities in the state of Minas Gerais, in the period from July to December
      2012. In the stage of face and content validity 17 items of the instrument were
      reduced. The factor analysis extracted eight factors that accounted for a
      percentage of 35.7% of the total variance. The principal components analysis
      allowed the elimination of eight items that showed no adaptation to the factors
      defined. The overall Cronbach alpha for the 57 items was 0.858. We conclude that
      the instrument is valid to evaluate the performance of primary care in leprosy
      control in the experience of ACS. 

PMID- 25054694
TI  - [Contributions of health education groups to the knowledge of people with
      hypertension].
AB  - This study investigated how the health knowledge is constructed by individuals
      with hypertension, accompanied by a team of family health. This is a qualitative
      descriptive study, conducted with nine individuals whose data were collected
      through semi-structured interviews and observation. The data was analyzed through
      thematic analysis. The construction of knowledge in health is influenced by many
      elements in the everyday life of the subjects. The dialogue and interaction with
      others are elements of greatest impact to build such knowledge. Thus, the health
      education group was pointed out as a relevant activity, both due to the
      explanations presented by the professionals, as well as the Exchange of knowledge
      and experiences with the other participants. It is concluded that although living
      the same pedagogical activities, the repercussions of the health education
      actions will take effect and will be noticed differently by the subjects. 

PMID- 25054695
TI  - [Association between prenatal care and neonatal deaths, 2000-2009, Londrina-PR].
AB  - The study aimed to analyze the prenatal care for mothers of infants who died in
      the neonatal period, in Londrina-PR, through a quantitative retrospective cohort
      study, between 2000 and 2009. Almost all women held the prenatal care (91.4 %),
      with 55.1 % up to six consultations. In ten years, the low number of visits (<=
      6) predominated. There was a statistically significant relationship between the
      number of prenatal visits and maternal sociodemographic variables (p < 0.004) and
      characteristics of the labor and the newborn (p < 0.001). The surgical delivery
      was predominant among women with >= 7 queries (71.3 %). Among women with <= 6
      prenatal visits, 65.9 % of births occurred before 32 weeks of gestation, 79.8 %
      of the newborns had Apgar scores <= 6 at 1 minute and 51.7 % weight <= 1000
      grams. Most deaths occurred in the early neonatal period (72.6 %). We highlight
      the necessity of qualitative and integrative prenatal care in this city,
      considering beyond biological conditions but also maternal socio-economic
      conditions in order to reduce neonatal deaths. 

PMID- 25054696
TI  - [Representations of the midwife in the perspective of the pregnant woman].
AB  - This study aimed to identify the social representations of the nurse specialist
      in maternal health and obstetrical care under the gaze of the pregnant woman
      using a qualitative study of 50 pregnant women in three municipalities of the
      Northwest Portugal, which carry out their antenatal care in the health center of
      their residence area. Data were collected through semi-structured interviews
      between February and July 2007 and analyzed based on content analysis. The
      results showed that the nurse midwife is faced as a friend, guide and support in
      helping to experience the whole process inherent in the birth. This research can
      be a contribution for the improvement of the quality of care provided during
      pregnancy. 

PMID- 25054697
TI  - [Abuse of alcohol and drugs and violence against women: experience reports].
AB  - This study aimed to analyze the interface between the abuse of alcohol and other
      drugs by companions and the experience of women who has denounced violence
      situations. It is a qualitative research guided by the thematic content analysis,
      with interviews conducted in March and April 2010, with thirteen women who
      underwent the record of violence in a Police Station for Women and Police
      Emergency Department of a city in the interior of Rio Grande do Sul, Brazil. It
      was observed that, in a world surrounded by fights, humiliation, aggression,
      submission and suffering, the companion's abuse of alcohol and drugs enhanced the
      violence experienced by the interviewed women. Besides seeking to qualify the
      mental health care of women in the context of violence, since this condition
      substantially affects their health, as well as all other dimensions, it appears
      to be essential to articulate attention to women in situations of violence with
      actions of prevention of alcohol and / or other drugs by their companions. 

PMID- 25054698
TI  - [Prevalence of alcoholism in the profile of disability retirement among employees
      of a federal university].
AB  - This study aimed to describe the causes of morbidity among servers retired for
      disability in a federal university; identify the socio-demographic and
      occupational profile of the retired for disability in general and for alcoholism;
      and make an association between these causes. This was a retrospective cross
      sectional descriptive study; the population consisted of all servers retired for
      disability registered at the university. The total disability retirees was of 553
      servers, especially in cases of retirement for psychiatric disorders (35.6%) as
      the leading cause of disability, and alcoholism led to the retirement of 9% of
      retirees. It was concluded that the highest percentage of disability retirement
      was composed of workers concentrated in the university hospital.

PMID- 25054699
TI  - [Sociodemographic profile of smokers admitted to the psychiatric ward of a
      general hospital].
AB  - From the interest of health professionals in tobacco control, stood out its high
      frequency in psychiatric population. This paper aimed to identify the socio
      demographic profile of psychiatric patients who are also smokers, comparing with
      former smokers and non smokers. Exploratory survey, conducted from August 2010 to
      February 2012, involving psychiatric patients hospitalized in a general hospital,
      through interviews using a structured questionnaire. Out of the 433 persons
      hospitalized, 270 took part of this study; 83.7% are carriers of severe mental
      disorders; 35.6% are smokers, 14.1% former smokers and 50.4% non smokers. Higher
      proportion of smokers was found among male, 30-49 years old, junior high
      schooling, rural area, separated/divorced, without occupation, income and
      religion practice. This profile is similar to smokers of other groups of
      population. There was difference in the profile of psychiatric patients according
      to smoking. This knowledge may help nurse to plan interventions, according the
      needs and possibilities of the subjects. 

PMID- 25054700
TI  - [Reasons attributed by professionals of an Intensive Care Unit for the absence at
      work].
AB  - This is an exploratory, descriptive study, with a qualitative approach, which
      aimed to identify the reasons attributed by nursing professionals for the
      absences at work; and to describe the alternatives proposed for the reduction of
      the absences in a teaching hospital. It was carried out in a Federal Public
      Hospital with 29 professionals from the Intensive Care Unit, the unit with the
      greater number of absences at work in 2008. Data were collected through focus
      groups and submitted to thematic content analysis. It was evidenced, as reasons
      for the occurrence of absenteeism, the influence of the physical environment,
      management and interpersonal skills. It was highlighted, as alternatives for the
      reduction of absences at work, the participatory management, team work, service
      organization and therapeutic support. It was concluded that the absenteeism
      involves subjective issues with multiple dimensions, which cannot be clarified
      only through quantitative perspective. 

PMID- 25054701
TI  - [Risk factors for cardiovascular diseases among nursing professionals: strategies
      for health promotion].
AB  - The objectives of this study are to identify modifiable and non-modifiable risk
      factors to cardiovascular diseases present in professional nursing and to
      describe strategies for health promotion to control and prevent these factors. It
      is a documentary and quantitative study, conducted with 165 professional nursing
      records of a public hospital in Fortaleza-CE. The analysis was made using
      descriptive statistics, with data presented in charts and tables. As a result it
      was found risk factors such as family history of arterial hypertension (72.9%),
      sedentary people (64.9%), overweight (56.4%), and high waist circumference
      (49.7%), among others. Regarding health promotion strategies, it can be
      mentioned: educational guidance, referrals and follow-up clinical data. It is
      believed in the need for special attention to such professionals, since they
      experience a stressful profession, facing problems such as job dissatisfaction,
      lack of financial recognition and some occupational diseases, which may impair
      their quality of life and hinder self-care.

PMID- 25054702
TI  - [Embracement and anxiety symptoms in patients before cardiac surgery].
AB  - This is a randomized clinical trial, aimed to compare the frequency and intensity
      of symptoms of anxiety in patients of preoperative cardiac surgery who received
      empathic behavior from nurse or family or those who received no specific type of
      empathic behavior. The sample consisted of 66 patients in preoperative of cardiac
      surgery, which were divided in three groups: empathic behavior by nurses, without
      specific empathic behavior and by family. Anxiety was assessed at two points in
      time: before and after the intervention. The instrument used was developed and
      validated by Suriano, comprising 19 defining characteristics of the nursing
      diagnosis anxiety. It was observed that the reduction of anxiety symptoms was
      higher in the group receiving empathic behavior of relatives when compared to the
      other two groups. The results suggested that encouraging the participation of
      family members can contribute to the reduction of anxiety symptoms in patients in
      preoperative cardiac surgery. 

PMID- 25054703
TI  - [Perceptions of family members of patients with cancer on musical encounters
      during the antineoplastic treatment].
AB  - Current research is a qualitative phenomenological analysis, structured on
      Heidegger's existential analysis, whose aim was the perception of cancer
      patients' relatives who live with subjects with cancer and with anticancer
      treatment, about the musical encounters. Five subjects living at the clinic run
      by the Maringa Female Network against Cancer participated at eight musical
      encounters during January and February 2011. The meeting mediated by the music
      can provide the relatives with a moment of existential introspection which lead
      them to a transcendental experience in coping with their existential condition.
      It inspired the expression of subjectivity and the revealing of their existential
      / spiritual needs. Within the context of cancer palliative care, the encounters
      may broaden the integration and humanization possibilities of nursing care to the
      family, providing comfort, reflection and motivation in the wake of emergent
      adversities within the clinic's temporal term.

PMID- 25054704
TI  - [Biopsychosocial determinants of the labor inclusion process of the person with a
      stoma].
AB  - This study focused the social determinants of people with an ostomy that
      facilitate and / or hamper their work inclusion. The objectives were to identify
      and analyze the difficulties and facilities for people with an ostomy for work
      inclusion. Descriptive exploratory, qualitative research, carried out with 20
      stomized through semi-structured interviews, using the Thematic Content Analysis.
      The results revealed that the main difficulties of ostomy to step into the
      working environment were the loss of sphincter control, social isolation and lack
      of opportunities suitable to your health condition new jobs. The main
      facilitators were the creation of adapted toilets and flexible schedules. We
      conclude that the biopsychosocial changes caused by the presence of the stoma may
      hinder inclusion in the work of ostomy patients, however, with social support can
      be created flexible terms that help them in their return to work activities. 

PMID- 25054705
TI  - [Modes of subjectivity production of nurses for decision making].
AB  - This study aimed to analyze the nurse's ways of production of subjectivity in
      decision-making processes that involve nursing care. We adopted qualitative
      research design. The investigative scenario was a philanthropic hospital in the
      State of Rio Grande do Sul. The study participants were twelve nurses working in
      this institution. For data collection, it was used the technique of focus group,
      with three focal meetings conducted in December 2011. From discussions among
      nurses, it was found that the nurse's ways of production of subjectivity
      oscillate between two extremes: a relationship of alienation and oppression,
      resulting in a self-protection, redundancy and domination behavior, or an
      expression and creation ratio, resulting in proactive behavior of nurses. Nurse's
      ways of production of subjectivity can condition and define behaviors that
      prevail in the decision making in care practice. 

PMID- 25054706
TI  - [Nursing diagnoses in patients undergoing prostatectomy: identification of the
      significance of its components].
AB  - Cross-sectional study conducted in a university hospital located in the Brazil's
      northeastern with 50 patients in the prostatectomy immediate postoperative. The
      study aimed to identify the defining characteristics and related/ risk factors
      that are associated with nursing diagnoses present in patients undergoing to
      prostatectomy. Nine nursing diagnoses that are statistically associated with
      related/ risk factors and defining characteristics were identified. We conclude
      that the considerable number of identified associations between nursing diagnoses
      and their elements shows that professionals, especially those in the urology
      clinic, should be prepared for the various care needs of this clientele. 

PMID- 25054707
TI  - [Applicability of ICNP(r) based on the theory of modeling and role-modeling].
AB  - This study aimed to analyze the proposal of educational plan organized through
      the Nursing Process, using the International Classification for Nursing Practice
      (ICNP(r)), based on the Theory of Modeling and Role Modeling, to one group of
      women in Maracanau-CE, Brazil. A case study was carried out in an educational
      group of women. A qualitative approach conducted the data production guided by
      the Creative and Sensitive Method. Two main diagnoses emerged from the needs
      presented by the group: compromised health and adequate knowledge, as well as
      formulation of results and nursing interventions. This study indicates the
      possibility of Nursing Process supported by INCP(r) and educational activities
      based on the Theory of Modeling and Role Modeling. 

PMID- 25054708
TI  - [Concept analysis of the nursing outcome Mobility in patients with stroke].
AB  - This study aimed a concept analysis of the nursing outcome Mobility in patients
      with stroke. A literature review was conducted, through the online access to
      databases: Scopus, Pubmed, CINAHL, Cochrane, and Lilacs, using the descriptors:
      mobility, stroke, nursing and their synonyms in Portuguese and Spanish. 1.521
      articles were identified, resulting in 49, after careful selection. Noteworthy
      are the articles published in Canada (26.7%), on 2001 (95.9%), by
      physiotherapists (34.6%), and in rehabilitation units (61.5%). The attributes
      identified for Mobility were: walking, standing, sitting, put the leg side to
      side, turn around, start and stop walking, stair climbing, motor function, and
      motor skill transfer. A model case and a contrary case were built, and
      identified, as antecedents: postural control and balance; and, as consequents:
      performs tasks inside and outside the house and wanders without difficulty. It
      was concluded that the concepts of Mobility found in this study need to be
      validated with experts in the field and in clinical practice.

PMID- 25054709
TI  - [Depressive symptoms in the elderly: comparison of residents in condominium
      specific for elderly and in the community].
AB  - This study aimed to compare the symptoms of depression among elderly living in a
      Condo for elderly and in the community. A quantitative study was conducted with
      210 elderly in the city of Maringa-PR. Data were collected between November 2011
      and February 2012, using the instrument BOAS, and subjected to statistical
      analysis. Among the subjects studied, 23.3% had depression, with an odds ratio of
      greater occurrence for residents of the Condominium. Despite the range of
      activities the organization of this housing type, it was observed that the
      elderly with depression are precisely those which by itself does not participate
      in the activities. It is therefore important that professionals identify early
      these elderly, to develop strategies to strengthen the bond in order to prevent
      the evolution of the situation and to contribute to the promotion of mental
      health and quality of life.

PMID- 25054710
TI  - [Evaluation of the computerized system of continuing education in nursing].
AB  - This study aimed to evaluate the data in the Computer System of Continuing
      Education in Nursing (SIEC), from the perspective of nurse specialists. In this
      exploratory study, seven experts attributed relevance / priority to the data set,
      through a questionnaire. The SIEC data set was evaluated with 70% of opinions,
      which confirms the user's satisfaction with respect to the content of the system,
      according to the Brazilian standard ISO / IEC 14598-1. Professional categories,
      institution and scientific production, data of technical visiting and
      professional skills of the teaching activity category, and the assessment report
      of the student category assessment were scored with borderline percentage of 71%
      (n=5). It was concluded that the SIEC data set is relevant / priority for
      Continuing Education Service, constituting a minimum data set required for this
      service. 

PMID- 25054711
TI  - [Nursing contribution in health decision making].
AB  - Decision making in health is a frequent situation, although potentially
      difficult, depending on patient/user characteristics and the context or the
      situation of health. This causes decisional conflicts in patients/users. The
      present study proposes to analyze the decision making process in health,
      conceptually, and nurses' contributions to understand and confront the
      phenomenon. The Ottawa the Model of Decisions Making in Health, proposed by
      Annette O'Connor, arises as a useful tool that enables nurses to carry out
      effective interventions with persons who face decision problems. Patients/users
      can assume a more active participation in the decisions on their own health.

PMID- 25054712
TI  - [Driving modes of the interview in phenomenological research: experience report].
AB  - This paper aimed to report the experience of driving modes of an interview on
      data production in phenomenological research. The proposed study is an experience
      report of a phenomenological investigation in which the researchers present their
      experience with children, considering the interview as an existential encounter.
      It describes ways of conducting the interview in its ontic and ontological
      dimensions. The ontic dimension refers to the facts related to the interview,
      presented in the researcher, in the researched subject and in the environment;
      both in its planning and its development. The ontological dimension is based on
      empathy and intersubjectivity. The interview enables the access to meaningful
      structures to comprehend the being, as a way of building investigative/assistance
      possibilities that enable to reveal the being of the human.

PMID- 25054714
TI  - One-pot stepwise approach to beta-enaminoketoesters through "masked" 1,3-aza
      dipoles.
AB  - t-BuOK-mediated rearrangement of 1,3-ketoesters with 2-(azidomethyl) aromatics in
      a two-step, one-pot telescoped sequence affords beta-enaminoketoesters in
      moderate to good yields. A novel pathway is proposed in which the umpolung of the
      azide is achieved from electrophilicity to nucleophilicity via deprotonation and
      undergoes nucleophilic attack onto the 1,3-ketoester. 

PMID- 25054715
TI  - Don't learn on me--are teaching hospitals patient-centered?

PMID- 25054716
TI  - Inhibition of the mTORC pathway in the antiphospholipid syndrome.
AB  - BACKGROUND: Although thrombosis is considered the cardinal feature of the
      antiphospholipid syndrome, chronic vascular lesions are common, particularly in
      patients with life-threatening complications. In patients who require
      transplantation, vascular lesions often recur. The molecular pathways involved in
      the vasculopathy of the antiphospholipid syndrome are unknown, and adequate
      therapies are lacking. METHODS: We used double immunostaining to evaluate pathway
      activation in the mammalian target of rapamycin complex (mTORC) and the nature of
      cell proliferation in the vessels of patients with primary or secondary
      antiphospholipid syndrome nephropathy. We also evaluated autopsy specimens from
      persons who had catastrophic antiphospholipid syndrome. The molecular pathways
      through which antiphospholipid antibodies modulate the mTORC pathway were
      evaluated in vitro, and potential pharmacologic inhibitors were also tested in
      vitro. Finally, we studied the effect of sirolimus in kidney-transplant
      recipients with the antiphospholipid syndrome. RESULTS: The vascular endothelium
      of proliferating intrarenal vessels from patients with antiphospholipid syndrome
      nephropathy showed indications of activation of the mTORC pathway. In cultured
      vascular endothelial cells, IgG antibodies from patients with the
      antiphospholipid syndrome stimulated mTORC through the phosphatidylinositol 3
      kinase (PI3K)-AKT pathway. Patients with antiphospholipid syndrome nephropathy
      who required transplantation and were receiving sirolimus had no recurrence of
      vascular lesions and had decreased vascular proliferation on biopsy as compared
      with patients with antiphospholipid antibodies who were not receiving sirolimus.
      Among 10 patients treated with sirolimus, 7 (70%) had a functioning renal
      allograft 144 months after transplantation versus 3 of 27 untreated patients
      (11%). Activation of mTORC was also found in the vessels of autopsy specimens
      from patients with catastrophic antiphospholipid syndrome. CONCLUSIONS: Our
      results suggest that the mTORC pathway is involved in the vascular lesions
      associated with the antiphospholipid syndrome. (Funded by INSERM and others.).

PMID- 25054718
TI  - Clinical practice. Care of the asplenic patient.

PMID- 25054717
TI  - HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry.
AB  - BACKGROUND: Hematopoietic stem-cell transplantation (HSCT) is a potentially
      lifesaving therapy for several blood cancers and other diseases. For patients
      without a suitable related HLA-matched donor, unrelated-donor registries of adult
      volunteers and banked umbilical cord-blood units, such as the Be the Match
      Registry operated by the National Marrow Donor Program (NMDP), provide potential
      sources of donors. Our goal in the present study was to measure the likelihood of
      finding a suitable donor in the U.S. registry. METHODS: Using human HLA data from
      the NMDP donor and cord-blood-unit registry, we built population-based genetic
      models for 21 U.S. racial and ethnic groups to predict the likelihood of
      identifying a suitable donor (either an adult donor or a cord-blood unit) for
      patients in each group. The models incorporated the degree of HLA matching, adult
      donor availability (i.e., ability to donate), and cord-blood-unit cell dose.
      RESULTS: Our models indicated that most candidates for HSCT will have a suitable
      (HLA-matched or minimally mismatched) adult donor. However, many patients will
      not have an optimal adult donor--that is, a donor who is matched at high
      resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an
      optimal donor varies among racial and ethnic groups, with the highest probability
      among whites of European descent, at 75%, and the lowest probability among blacks
      of South or Central American descent, at 16%. Likelihoods for other groups are
      intermediate. Few patients will have an optimal cord-blood unit--that is, one
      matched at the antigen level at HLA-A and HLA-B and matched at high resolution at
      HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are
      available for almost all patients younger than 20 years of age and for more than
      80% of patients 20 years of age or older, regardless of racial and ethnic
      background. CONCLUSIONS: Most patients likely to benefit from HSCT will have a
      donor. Public investment in donor recruitment and cord-blood banks has expanded
      access to HSCT. (Funded by the Office of Naval Research, Department of the Navy,
      and the Health Resources and Services Administration, Department of Health and
      Human Services.).

PMID- 25054719
TI  - Images in clinical medicine. Dahl's sign.

PMID- 25054720
TI  - Case records of the Massachusetts General Hospital. Case 23-2014. A 41-year-old
      man with fevers, rash, pancytopenia, and abnormal liver function.

PMID- 25054721
TI  - The mTORC pathway in the antiphospholipid syndrome.

PMID- 25054722
TI  - FDA regulation of mobile health technologies.

PMID- 25054723
TI  - Parallels between cancer and infectious disease.

PMID- 25054724
TI  - Protocol-based care for early septic shock.

PMID- 25054725
TI  - Protocol-based care for early septic shock.

PMID- 25054726
TI  - Protocol-based care for early septic shock.

PMID- 25054727
TI  - Protocol-based care for early septic shock.

PMID- 25054728
TI  - Protocol-based care for early septic shock.

PMID- 25054729
TI  - Case 9-2014: A woman with increasing dyspnea.

PMID- 25054730
TI  - Case 9-2014: A woman with increasing dyspnea.

PMID- 25054731
TI  - Case 9-2014: A woman with increasing dyspnea.

PMID- 25054732
TI  - A randomized trial of robot-assisted laparoscopic radical cystectomy.

PMID- 25054734
TI  - Clinical decisions. Starting statins--polling results.

PMID- 25054733
TI  - Images in clinical medicine. Internal carotid artery in the middle ear.

PMID- 25054735
TI  - 3D reconstruction of scintillation light emission from proton pencil beams using
      limited viewing angles-a simulation study.
AB  - An accurate and high-resolution quality assurance (QA) method for proton
      radiotherapy beams is necessary to ensure correct dose delivery to the target.
      Detectors based on a large volume of liquid scintillator have shown great promise
      in providing fast and high-resolution measurements of proton treatment fields.
      However, previous work with these detectors has been limited to two-dimensional
      measurements, and the quantitative measurement of dose distributions was lacking.
      The purpose of the current study is to assess the feasibility of reconstructing
      three-dimensional (3D) scintillation light distributions of spot scanning proton
      beams using a scintillation system. The proposed system consists of a tank of
      liquid scintillator imaged by charge-coupled device cameras at three orthogonal
      viewing angles. Because of the limited number of viewing angles, we developed a
      profile-based technique to obtain an initial estimate that can improve the
      quality of the 3D reconstruction. We found that our proposed scintillator system
      and profile-based technique can reconstruct a single energy proton beam in 3D
      with a gamma passing rate (3%/3 mm local) of 100.0%. For a single energy layer of
      an intensity modulated proton therapy prostate treatment plan, the proposed
      method can reconstruct the 3D light distribution with a gamma pass rate (3%/3 mm
      local) of 99.7%. In addition, we also found that the proposed method is effective
      in detecting errors in the treatment plan, indicating that it can be a very
      useful tool for 3D proton beam QA. 

PMID- 25054736
TI  - Sex differences in cardiovascular health: does sexism influence women's health?
AB  - This commentary provides a brief overview of theory and research that supports
      the idea that sexism may be related to the disproportionate negative
      cardiovascular health outcomes in women. It describes sexism as a stressor and
      outlines its association with a variety of health outcomes as evidence for why
      sex disparities should be examined within the context of pervasive inequities. To
      date, population-based studies have not explicitly examined the relationship
      between sexism and cardiovascular disease, but smaller studies have yielded
      fairly consistent results. It is suggested that future research should aim to
      examine the influence of 2 types of sexism (ie, hostile and benevolent) and that
      daily or within-day designs be used to assess cognitive, behavioral and
      physiological responses to everyday sexist experiences.

PMID- 25054737
TI  - Decreased interleukin 35 and CD4+EBI3+ T cells in patients with active systemic
      lupus erythematosus.
AB  - BACKGROUND: Interleukin 35 (IL-35) is likely to contribute to the development of
      autoimmune diseases, as the Epstein-Barr virus-induced gene protein 3 (EBI3) is
      the specificity subunit of IL-35. Nevertheless, until recently, no studies have
      evaluated its role in systemic lupus erythematosus (SLE) in humans. The objective
      of this study was to investigate the serum IL-35 level and the percentage of
      CD4EBI3 T cells in the peripheral blood of patients with SLE and explore the
      roles of double-positive T cells and IL-35 in the pathogenesis of SLE and the
      effects of glucocorticoid on these roles. METHODS: Fifty-five hospitalized
      patients with SLE were recruited, and 20 volunteers were enrolled as healthy
      controls. Serum IL-35 levels were measured by enzyme-linked immunosorbent assay,
      and the percentage of CD4EBI3 T cells was analyzed by flow cytometry. RESULTS:
      The serum IL-35 level and the percentage of CD4EBI3 T cells were significantly
      decreased in patients with active SLE compared with healthy controls and patients
      with inactive SLE. The serum IL-35 level and the percentage of CD4EBI3 T cells
      were negatively correlated with the SLE disease activity index. The percentages
      of CD4EBI3 T cells and serum IL-35 levels in 10 untreated patients with active
      SLE were increased at days l, 3, and 7 after the treatment with
      methylprednisolone (0.8 mg.kg.d) compared with the percentages before the
      treatment. CONCLUSIONS: These results demonstrate that abnormalities in IL-35 and
      CD4EBI3 T cells may play important roles in the pathogenesis of SLE; the
      percentage of double-positive T cells and the level of IL-35 are parameters for
      the evaluation of SLE activity and severity.

PMID- 25054738
TI  - Drug abuse and the simplest neurotransmitter.
AB  - Neurotransmitter vesicles are known to concentrate hydrogen ions (or protons),
      the simplest ion, and to release them during neurotransmission. Furthermore,
      receptors highly sensitive to protons, acid-sensing ion channels (ASICs), were
      previously localized on the opposite side of the synaptic cleft on dendritic
      spines. Now, recent experiments provide some of the strongest support to date
      that protons function as a neurotransmitter in mice, crossing synapses onto
      medium spiny neurons of the nucleus accumbens (NAc), activating ASICs, and
      ultimately suppressing drug abuse-related behaviors. 

PMID- 25054739
TI  - Cutaneous tuberculosis: diagnosis, histopathology and treatment - part II.
AB  - The evolution in the knowledge of tuberculosis' physiopathology allowed not only
      a better understanding of the immunological factors involved in the disease
      process, but also the development of new laboratory tests, as well as the
      establishment of a histological classification that reflects the host's ability
      to contain the infectious agent. At the same time, the increasing bacilli
      resistance led to alterations in the basic tuberculosis treatment scheme in 2009.
      This article critically examines laboratory and histological investigations,
      treatment regimens for tuberculosis and possible adverse reactions to the most
      frequently used drugs. 

PMID- 25054740
TI  - Evaluation of cases of pemphigus vulgaris and pemphigus foliaceus from a
      reference service in Para state, Brazil.
AB  - BACKGROUND: Pemphigusis a bullous, rare and chronic autoimmune disease. There are
      two major forms of pemphigus: vulgaris and foliaceus. Epidemiological data and
      clinical outcome in patients diagnosed in the Brazilian Amazon states are still
      rare. OBJECTIVES: To study the occurrence of the disease during the study period
      and analyze the epidemiological profile of patients, the most common subtype of
      pemphigus, and the clinical evolution of patients. METHODS: Retrospective
      analysis of medical records of hospitalized patients with pemphigus foliaceus and
      pemphigus vulgaris in the period from 2003 to 2010 in Dermatology Service of
      Hospital Fundacao Santa Casa de Misericordia do Para, Belem, Northern Brazil.
      RESULTS: We found a total of 20 cases of pemphigus during the study period, 8 of
      which were of foliaceus pemphigus and 12 of vulgaris pemphigus. Pemphigus
      foliaceus had the predominance of male patients (75%), showed satisfactory
      clinical evolution, and was characterized by absence of pediatric cases.
      Pemphigus vulgaris affected more women (66.7%), showed mean hospital stay of 1 to
      3 months (50%), and there were three cases of death (25%). The prescribed
      immunosuppressive drugs included prednisone with or without combination of
      azathioprine and/or dapsone. Sepsis was associated with 100% of the deaths.
      CONCLUSIONS: The occurrence of the disease is rare, there are no familiar/endemic
      outbreaks in the sample. Evolution is usually favorable, but secondary infection
      is associated with worse prognosis. The choice of best drugs to treat pemphigus
      remains controversial.

PMID- 25054741
TI  - Invasive head and neck cutaneous squamous cell carcinoma: clinical and
      histopathological characteristics, frequency of local recurrence and metastasis.
AB  - BACKGROUND: squamous cell carcinoma is the second most common type of skin
      malignancy and may evolve to regional lymph node and distant metastases.
      OBJECTIVE: The objective of this study was to evaluate patients with head and
      neck cutaneous squamous cell carcinoma to identify its clinical and
      histopathological characteristics, as well as the frequency of local recurrence
      and metastasis. METHODS: A retrospective cohort of patients with head and neck
      cutaneous squamous cell carcinoma. INCLUSION CRITERIA: histopathological
      confirmation, follow-up for longer than one year after diagnosis. EXCLUSION
      CRITERIA: immunosuppression; lip and oral cavity squamous cell carcinoma; and non
      surgical resection of the lesion. We evaluated demographic, clinical and
      anatomopathologic findings and explored their associations. RESULTS: Sixty-one
      patients with 79 tumors and followed by 4.8+/-3.0 years were selected. The
      average age was 67.1 years, and 63% of tumors had up to two centimeters. Seven
      tumors (8.9%) recurred and two of them had positive margins. Recurrence was
      associated with higher Broders' grade (p<0.01). Two patients (3.3%) had regional
      lymph node metastases. There were no distant metastases. Seventy tumors were
      considered to be usual tumors (89.7%), and 68 (87.2%) were classified as Broders'
      grade 1 and 2. Additionally, 64.1% of tumors had a depth of invasion below four
      millimeters. Thirteen tumors (16.7%) had positive histological margins.
      CONCLUSIONS: Most patients had good prognosis in the first year of follow-up,
      confirming that head and neck cutaneous squamous cell carcinoma has a better
      prognosis than squamous cell carcinoma of other regions such as mucosa, oral
      cavity, and internal organs.

PMID- 25054743
TI  - Dissatisfaction and acne vulgaris in male adolescents and associated factors.
AB  - BACKGROUND: Acne vulgaris has high prevalence, disturbing quality of life during
      adolescence. OBJECTIVES: To measure dissastifaction and acne in 18-year-old male
      individuals and its associated factors. METHODS: A questionnaire was applied by
      trained interviewers to all boys during selection for the military service.
      Dissatisfaction and acne was evaluated using a self-administered face scale.
      Facial, prestrernal and dorsal acne were evaluated separately. RESULTS: A total
      of 2,200 adolescents, aged 18 years, were interviewed. Among these, 1,678 had
      acne on the face and 974 (54.05%) showed some degree of dissatisfaction.
      Regarding the impact of acne located on the chest, 326 out of 686 adolescents
      (47.52%) reported dissatisfaction. For acne located on the back, 568 out of 1,103
      affected individuals (51.50%) showed dissatisfaction. Facial / dorsal acne and
      dissatisfaction were statistically associated with lower income, lower education
      levels and with non-whites. Presternal acne and dissatisfaction were
      statistically asssociated with lower income and lower education levels.
      CONCLUSION: This population-based study found a high prevalence of acne on the
      face, back and chest, with high rates of dissatisfaction.

PMID- 25054742
TI  - Efficacy of gabapentin in the improvement of pruritus and quality of life of
      patients with notalgia paresthetica.
AB  - BACKGROUND: notalgia paresthetica is a subdiagnosed sensory neuropathy presenting
      as a condition of intense itching and hyperchromic macule on the back that
      interferes with daily habits. OBJECTIVES: To determine the efficacy of treatment
      of notalgia paresthetica using oral gabapentin, assessing the degree of
      improvement in itching and influence on quality of life. Moreover, to evaluate
      the signs and symptoms associated with notalgia paresthetica. METHODS: We
      conducted an experimental, non-randomized, parallel, non-blinded study including
      20 patients with clinical and histopathological diagnosis of notalgia
      paresthetica. After application of the visual analogue scale of pain adapted for
      pruritus and of the questionnaire of dermatology life quality index (DLQI), ten
      patients with visual analogue scale > 5 were given treatment with gabapentin at
      the dose of 300 mg/day for four weeks. The other ten were treated with topical
      capsaicin 0.025% daily for four weeks. After the treatment period, patients
      answered again the scale of itching. RESULTS: The use of gabapentin was
      responsible for a significant improvement in pruritus (p=0.0020). Besides itching
      and hyperchromic stain on the back, patients reported paresthesia and back pain.
      It was observed that the main factor in the worsening of the rash is heat.
      CONCLUSION: Gabapentin is a good option for the treatment of severe itching
      caused by nostalgia paresthetica.

PMID- 25054744
TI  - Onychomycosis: clinical, mycological and in vitro susceptibility testing of
      isolates of Trichophyton rubrum.
AB  - BACKGROUND: Onychomycosis or nail fungal infection is the most common nail
      disease. Despite the wide range of studies on this condition, it remains
      difficult to establish the correct diagnosis and effective treatment. OBJECTIVES:
      To evaluate the efficacy of classical laboratory methods for the diagnosis of
      onychomycosis, and the in vitro susceptibility of the its main etiological agent
      to antifungals used in routine. METHODS: Nail samples of 100 patients with
      clinically suspected feet onychomycosis were collected to confirm the diagnosis
      by direct mycological examination and fungal culture. In vitro antifungal
      susceptibility testing was performed against strains of the main dermatophyte
      isolated by microdilution, according to the standardized protocol (M38-A2 - CLSI)
      RESULTS: Clinical diagnosis of onychomycosis was confirmed by laboratory analysis
      in 59% of patients. Of these, 54.2% were positive only in direct mycological
      examination, 44.1% in direct mycological examination and culture, and one case
      (1.7%) was positive only in culture, resulting in weak agreement between these
      tests (Kappa = 0.385; p <0.001) High minimum inhibitory concentration values of
      fluconazole and itraconazole were observed in 66.7% and 25.0% of isolates of T.
      rubrum tested. Additionally, high MIC values of terbinafine and ciclopirox was
      detected in only one isolate, and this was one of the strains in which in vitro
      activity of itraconazole and fluconazole has not been proven. CONCLUSIONS: Poor
      agreement was observed between direct mycological examination and culture for the
      diagnosis of onychomycosis, with direct mycological examination being
      significantly more sensitive. Except for fluconazole, the other three antifungals
      tested showed good in vitro activity against clinical isolates of T. rubrum.

PMID- 25054745
TI  - Sports-related dermatoses among road runners in Southern Brazil.
AB  - BACKGROUND: Road running is a growing sport. OBJECTIVES: To determine the
      prevalence of sports-related dermatoses among road runners. METHODS: Cross
      sectional study of 76 road runners. Assessment was performed by means of a
      questionnaire, interview, and clinical examination. The chi-square and linear
      trend tests were used for analysis. RESULTS: Most athletes were men (61%), aged
      38+/-11 years, who ran mid- or long-distance courses (60.5%) for 45 to 60 minutes
      (79%), for a total of 25-64 km (42.1% ) or more than 65 km (18.4%) per week. The
      most prevalent injuries were blisters (50%), chafing (42.1%), calluses (34.2%),
      onychomadesis (31.5%), tinea pedis (18.4%), onychocryptosis (14.5%), and
      cheilitis simplex (14.5%). Among athletes running >64 km weekly, several
      conditions were significantly more frequent: calluses (p<0.04), jogger's nipple
      (p<0.004), cheilitis simplex (p<0.05), and tinea pedis (p<0.004). There was a
      significant association between the weekly running distance and the probability
      of skin lesions. Of the athletes in our sample, 57% trained before 10 a.m., 86%
      wore clothing and accessories for sun protection, 62% wore sunscreen, and 19.7%
      experienced sunburn. Traumatic and environmental dermatoses are common in
      practitioners of this outdoor sport, and are influenced by the weekly running
      distance. CONCLUSION: In this group of athletes, rashes, blisters, sunburn, and
      nail disorders were recurrent complaints regardless of running distance.
      Calluses, athlete's foot, chapped lips, and jogger's nipple predominated in
      individuals who ran longer routes.

PMID- 25054746
TI  - Quality of life and self-esteem in patients submitted to surgical treatment of
      skin carcinomas: long-term results.
AB  - BACKGROUND: Cancer is a multifactorial disease and skin carcinomas are the most
      common type of cancer. Assessing quality of life and self-esteem outcomes in skin
      cancer patients is important because these are indicators of the results of the
      treatment, translating how patients face their lives and their personal
      relationships. OBJECTIVE: To assess the late impact of the surgical treatment of
      head and/or neck skin carcinomas on quality of life and self-esteem of the
      patients. METHODS: Fifty patients with head or neck skin carcinomas were
      enrolled. Their age ranged between 30 and 75 years, 27 were men and 23 were
      women. Patients were assessed with regard to quality of life and self-esteem,
      preoperatively and five years postoperatively. Validated instruments were used:
      the MOS 36-item Short-form Health Survey (SF-36) and the Rosenberg Self
      esteem/EPM-UNIFESP Scale. The Wilcoxon signed-rank test was used for the
      statistical analysis. RESULTS: Twenty-two patients completed the five-year follow
      up, 54.5% women and 45.5% men. Compared to the preoperative assessment, patients
      had an improvement in mental health (p=0.011) and in self-esteem (p=0.002). There
      was no statistical difference with regard to the other domains of the SF-36.
      CONCLUSION: Patients submitted to surgical treatment of skin carcinoma improved
      mental health and self-esteem in the late postsurgical testing.

PMID- 25054747
TI  - Translation, cultural adaptation, and validation of the American Skindex-29
      quality of life index.
AB  - BACKGROUND: Measuring the quality of life measure of patients with dermatologic
      diseases is an important concern. The instruments to evaluate it are commonly
      originally written in English and need to be translated and validated to be used
      in different cultures. OBJECTIVE: The purpose of this paper is to translate and
      validate the Skindex-29 questionnaire to Brazilian Portuguese to be used in our
      country as a quality of life assessment instrument in dermatologic patients.
      METHODS: The first step was the translation from English to Brazilian Portuguese
      and the back-translation by two native speakers. The translated version was then
      used for the second step, when three questionnaires were applied to 75 patients
      (43 of whom were classified as lightly affected and 32 as heavily affected by
      their dermatologic conditions): an identification questionnaire, the translated
      version of Skindex-29, and the Brazilian Portuguese version of Dermatologic Life
      Quality Index (DLQI). Additionally, the generic questionnaire Short Form 36 (SF
      36) was applied to 41 of these patients. The last step to evaluate
      reproducibility was repeating the Skindex-29 questionnaire by the same researcher
      one week later in 44 patients. RESULTS: Reliability was observed in global
      Skindex-29 scale (alpha=0.934), and its domains emotions (alpha=0.926), symptoms
      (alpha=0,702), and psycosocial functioning (alpha=0.860). The reproducibility
      showed high intraclass correlations. High intra class correlations was observed,
      thus validating reliability. CONCLUSIONS: The Skindex-29 quality of life
      questionnaire was properly translated and validated to Brazilian Portuguese.

PMID- 25054748
TI  - Sample size: how many participants do I need in my research?
AB  - The importance of estimating sample sizes is rarely understood by researchers,
      when planning a study. This paper aims to highlight the centrality of sample size
      estimations in health research. Examples that help in understanding the basic
      concepts involved in their calculation are presented. The scenarios covered are
      based more on the epidemiological reasoning and less on mathematical formulae.
      Proper calculation of the number of participants in a study diminishes the
      likelihood of errors, which are often associated with adverse consequences in
      terms of economic, ethical and health aspects. 

PMID- 25054750
TI  - Prevalence of self-medication for skin diseases: a systematic review.
AB  - Self-medication is the selection and use of drugs without medical prescription,
      to treat diseases or for symptomatic relief. This article is a systematic review
      on self-medication in skin diseases. A search was conducted on Virtual Health
      Library and PubMed databases using predetermined descriptors. Two researchers
      performed the article selection process independently, with the degree of inter
      observer agreement measured by the kappa index. The prevalence of self-medication
      ranged from 6.0 to 45.0%. Topical corticosteroids were the most commonly used
      therapeutic strategies for self-medication, as found in the reviewed articles.
      This study revealed that published data on self-medication in dermatology are
      scarce, although the findings showed that it was a common practice. 

PMID- 25054749
TI  - Effects of low-power light therapy on wound healing: LASER x LED.
AB  - Several studies demonstrate the benefits of low-power light therapy on wound
      healing. However, the use of LED as a therapeutic resource remains controversial.
      There are questions regarding the equality or not of biological effects promoted
      by LED and LASER. One objective of this review was to determine the biological
      effects that support the use of LED on wound healing. Another objective was to
      identify LED's parameters for the treatment of wounds. The biological effects and
      parameters of LED will be compared to those of LASER. Literature was obtained
      from online databases such as Medline, PubMed, Science Direct and Scielo. The
      search was restricted to studies published in English and Portuguese from 1992 to
      2012. Sixty-eight studies in vitro and in animals were analyzed. LED and LASER
      promote similar biological effects, such as decrease of inflammatory cells,
      increased fibroblast proliferation, stimulation of angiogenesis, granulation
      tissue formation and increased synthesis of collagen. The irradiation parameters
      are also similar between LED and LASER. The biological effects are dependent on
      irradiation parameters, mainly wavelength and dose. This review elucidates the
      importance of defining parameters for the use of light devices. 

PMID- 25054751
TI  - Oral chronic graft-versus-host disease: analysis of dendritic cells
      subpopulations.
AB  - The graft-versus-host disease is the major cause of morbidity and mortality in
      patients who have undergone hematopoietic stem cell transplantation. Aiming at
      contributing to the understanding of the role of myeloid and plasmacytoid
      dendritic cells, and natural killer cells in chronic graft-versus-host disease,
      we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia
      who had undergone allogenic hematopoietic stem cell transplantation. Half of
      these patients developed oral chronic graft-versus-host disease. Microscopic
      sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti
      CD56. We calculated the number of immunostained cells in the corium per square
      millimeter and applied the Mann-Whitney test. Results showed a statistically
      significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural
      killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host
      disease. CD123 immunostaining showed no statistical difference between groups. It
      was concluded that myeloid dendritic cells and natural killer cells participate
      in the development of oral chronic graft-versus-host disease. 

PMID- 25054752
TI  - Application of platelet-rich plasma in the treatment of chronic skin ulcer - case
      report.
AB  - The platelet-rich plasma (PRP) has proved promising regarding its applicability
      in dermatology, especially in the healing of chronic ulcers. The autologous
      platelet-rich plasma is obtained by centrifuging the blood, so that the
      components are separated by density gradient. The final product is a gel rich in
      growth factors that act in tissue repair by activating fibroblasts and inducing
      extracellular matrix remodeling. 

PMID- 25054753
TI  - Chronic mucocutaneous candidiasis: a case with exuberant cutaneous horns in
      nipples.
AB  - Chronic mucocutaneous candidiasis is a rare disorder characterized by persistent
      and recurrent infections by Candida due to changes in cellular immunity and may
      be associated with autoimmune endocrine disorders. It is refractory to the usual
      antifungal treatments, which merely control it with imidazole derivatives. This
      reports the case of a 50-year-old female patient who referred vaginal discharge
      associated with vulvar ulcerated lesions and whitish plaques on oral and genital
      mucous membranes of onset in adolescence besides cutaneous horns in nipples. The
      clinical picture, family history, culture and anatomopathological studies were
      consistent with chronic infection by candida. Treatment with systemic antifungals
      obtained partial response of lesions characterizing a clinical picture of Chronic
      Mucocutaneous Candidiasis. 

PMID- 25054754
TI  - Ectopic cutaneous schistosomiasis - case report.
AB  - Schistosomiasis is best known in its visceral form but it can attack the skin,
      its ectopic cutaneous manifestation being rare and clinically difficult to
      diagnose. It is characterized by isolated or coalescent papules, erythematous,
      pruritic or asymptomatic, with zosteriform distribution, often located on the
      trunk. The authors report a case of a 28-year-old female patient with lesions on
      the abdomen, with positive stool results for Schistosoma and absence of active
      symptoms of visceral disease. The case reveals rare exuberant cutaneous
      manifestation and the importance of the diagnosis of this entity in patients from
      endemic regions. 

PMID- 25054755
TI  - Phaeohyphomycosis of the ungual apparatus - case report.
AB  - Phaeohyphomycosis is a disease caused by dematiaceous fungi with a worldwide
      geographic distribution and broad spectrum. It is most commonly found in adult
      individuals of both genders and all races. We report the case of a 57-year-old
      woman with phaeohyphomycosis in the ungual apparatus. 

PMID- 25054756
TI  - The use of ustekinumab in a patient with severe psoriasis and positive HBV
      serology.
AB  - Psoriasis is a chronic inflammatory, immune-mediated disease that affects 1% to
      2% of the world's population. Immunobiological medications are prescribed for
      certain patients with severe forms of psoriasis, however, these drugs increase
      the risk of reactivation of viral diseases such as hepatitis B. We report the
      case of a patient with severe psoriasis with positive serology for the Hepatitis
      B virus, who received ustekinumab (a human monoclonal antibody against
      interleukin 12 and 23). In this patient, the use of ustekinumab did not
      reactivate the Hepatitis B virus. Given the high prevalence of chronic viral
      infections in patients who are candidates for biologic therapy, as well as the
      potential for reactivate chronic viral illness, randomized controlled studies are
      needed to assess the risks and benefits of such therapy in these populations. 

PMID- 25054757
TI  - Poikilodermatous changes on the forearms of a woman practicing aroma-therapy:
      extracervical poikiloderma of Civatte?
AB  - We report the case of a 48-year-old, Caucasian female who presented with slowly
      progressing asymptomatic poikilodermatous changes of the extensor aspects of the
      forearms. She also had typical Poikiloderma of Civatte on the V of the neck and
      erythemato-telangiectatic rosacea of the central face. The patient had been
      practicing aroma-therapy for many years. Histologic examination revealed findings
      consistent with PC. Patch-testing revealed positive reactions to Fragrance mix
      and Nickel sulphate. Based on clinical and histological findings, a diagnosis of
      extracervical PC was suggested. PC with extra-cervical or extra-facial
      involvement is rare. In addition, this case supports the theory that contact
      sensitization to fragrances may contribute to the development of PC. 

PMID- 25054758
TI  - Pseudo-acne fulminans associated with oral isotretinoin.
AB  - Acne fulminans is a rare and serious condition characterized by the sudden onset
      of nodular and ulcerative acne lesions associated with systemic symptoms. It has
      been recognized a subset of patients with a sudden worsening of acne, often
      during treatment with oral isotretinoin, but without the strong presence of
      systemic involvement. Recognized by some authors as "pseudo-acne fulminans" or "
      acne fulminans sine fulminans," we report a case with these features in order to
      draw attention to the recognition and early management of this manifestation. 

PMID- 25054759
TI  - Musculoskeletal and cutaneous sarcoidosis: exuberant case report.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown cause. The
      osteoarticular involvement in sarcoidosis is rare and is often associated with
      cutaneous and long-standing chronic multisystem disease. More common in black
      women, osseous sarcoidosis is difficult to diagnose, with an incidence of 3 to
      13%. The most characteristic radiological clinical picture evidences rounded,
      well-defined cysts, with no periosteal reaction and without peripheral sclerosis.
      The small bones of hands and feet are the most frequently involved sites. This
      report aims to demonstrate a rare case of osteoarticular sarcoidosis with
      characteristic clinical presentation, and highlight the importance of detecting
      osteoarticular involvement in this pathology. 

PMID- 25054760
TI  - Dermoscopy as an auxiliary tool for the diagnosis of furuncular myiasis.
AB  - Furuncular myiasis occurs after larvae penetrate on the skin. The disease is
      characterized by the presence of a nodule with a central hole through which there
      is serosanguinous exudate drainage. The authors present a case of furuncular
      myiasis by Dermatobia hominis in which late diagnosis made it necessary to have
      the orifice margins surgically enlarged in order to extract the larva. They also
      emphasize that dermoscopy is a useful auxiliary tool in this diagnosis. 

PMID- 25054761
TI  - Polypoid melanoma and superficial spreading melanoma different subtypes in the
      same lesion.
AB  - Melanoma is a malignant melanocytic neoplasm with high mortality rate, and
      steadily and universally increasing incidence rates. Polypoid melanoma is
      considered an exophytic variant of the nodular subtype. The incidence of polypoid
      melanoma is extremely variable, most likely because of the different criteria
      used for its characterization. We presented a rare case of polypoid melanoma and
      superficial spreading melanoma in the same lesion. 

PMID- 25054762
TI  - Cutaneous New World Leishmaniasis on a Port-wine stain birthmark.
AB  - We present an interesting case report of two sarcoid-like lesions on a port-wine
      stain (PWS) birthmark in a Brazilian patient which on investigation proved to be
      cutaneous leishmaniasis. 

PMID- 25054763
TI  - Case for diagnosis.
AB  - Idiopathic Atrophoderma of Pasini and Pierini (IAPP) is a rare, exclusively
      cutaneous disease. It is more frequent in females, with incidence peak in the
      second and third decades of life. The etiopathogenesis remains unknown. IAPP most
      commonly affects the back, abdomen and proximal regions of the limbs. Lesions may
      be rounded, oval or circular; single or multiple. The evolution is variable and
      the course is initially progressive. Collagen changes such as atrophy, thinning,
      condensation and sclerosis may be observed in the papillary dermis. This paper
      describes a case of Idiopathic Atrophoderma of Pasini and Pierini with
      histopathologic findings. 

PMID- 25054764
TI  - Case for diagnosis.
AB  - We report the case of a 81-year-old female patient who had a two-year history of
      violet-colored erythematous tumors on both legs. Histopathological and
      immunohistochemical examinations confirmed the diagnosis of primary cutaneous
      large B-cell lymphoma, leg type. This rare, cutaneous lymphoma affects
      predominantly elderly females. Clinically, patients present with tumoral lesions
      on one or both legs (worst prognosis). Diagnosis is based on clinical,
      histopathological and immunohistochemical findings. The strong expression of
      BCL2, BCL6, MUM-1 and CD20, and the positivity for Ki67 antigen confirm the
      diagnosis. R-CHOP chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin,
      vincristine and prednisone) is the most widely accepted treatment. 

PMID- 25054765
TI  - Case for diagnosis.
AB  - Intravascular papillary endothelial hyperplasia is a benign vascular lesion
      caused by proliferation of endothelium. It is reactive to thrombotic or
      inflammatory stimuli in the vessel wall.We report the case of a 14-yearold male
      patient with a violet-colored erythematous tumoral lesion of progressive growth
      in the occipital region. The diagnosis of intravascular papillary endothelial
      hyperplasia (IPEH) was confirmed by clinical and histopathological findings.
      Total lesion exeresis was performed with no recurrence up to date. IPEH presents
      clinical importance due to its clinical and histological resemblance to
      angiosarcoma. In order to differentiate it from angiosarcoma, distinguishing
      features of the benign disease should be considered, such as lack of cellular
      atypia and rare mitotic activity.Prognosis is good. 

PMID- 25054766
TI  - Syndrome in question.
AB  - Rendu-Osler-Weber Syndrome also known as Hereditary Hemorrhagic Telangiectasia is
      a rare systemic fibrovascular dysplasia, with dominant autosomal inheritance. It
      is characterized by recurrent epistaxis, mucocutaneous telangiectasia, visceral
      arteriovenous malformation and positive family history. There may be hematologic,
      neurologic, dermatologic and gastrointestinal complications. Therapy is
      supportive and aimed at preventing complications. In this article we report a
      case of Rendu-Osler-Weber in a 64 year-old man, with history of mucocutaneous
      telangiectasia since the third decade of life, recurrent epistaxis, positive
      family history and vascular ectasia in the gastrointestinal tract. 

PMID- 25054767
TI  - Epidermal curettage technique (ECT) for tissue harvest from the donor area for
      melanocyte autologous grafting in cases of vitiligo.
AB  - Vitiligo is a dermatosis requiring complex treatment. In clinically stable cases,
      melanocyte autologous grafting has shown good results, using different
      methodologies for obtaining the donor area: dermatomes, punches, blisters.
      However, these techniques are complex and require specific instruments. This
      study presents a simple technique for melanocyte harvest that has been performed
      in our service for more than ten years and includes epidermal curettage of the
      donor area, grafting of the obtained material, which was homogenized with saline
      or hyaluronic acid, on the achromic area, and the application of a semipermeable
      dressing that is removed 1 week later. 

PMID- 25054768
TI  - Trichostasis spinulosa of the scalp mimicking Alopecia areata black dots.
AB  - Alopecia areata is a common autoimmune disorder that leads to nonscarring hair
      loss. Black dots, also called comedo-like cadaver hairs, can be found in almost
      50% of alopecia areata patients and indicate disease activity. Trichostasis
      spinulosa is a follicular disorder resulting from the retention of numerous hairs
      surrounded by a keratinous sheath in dilated follicles. Trichostasis spinulosa is
      a relatively common but underdiagnosed disorder of hair follicles. Here, we
      describe a man with alopecia areata of the eyebrows, androgenetic alopecia and
      trichostasis spinulosa at the vertex and show how dermoscopy can be useful in
      distinguishing black dots from Trichostasis spinulosa lesions. 

PMID- 25054769
TI  - Porphyria cutanea tarda and Sjogren's syndrome.
AB  - Porphyria cutanea tarda is prevalent in connective tissue disease, common in
      systemic lupus erythematosus. However, the co-existence of primary sjogren's
      syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic
      challenges. We report a case of porphyria cutanea tarda associated with primary
      sjogren's syndrome. 

PMID- 25054771
TI  - Gold(I)-catalyzed synthesis of optically active 1,4-oxazepan-7-ones.
AB  - Optically active seven-membered lactones, dimethyleneoxazepanones, were readily
      prepared in good yields from chiral beta-(N-propargylic)amino-alpha-methylene
      carboxylic acid tert-butyl esters in the presence of catalytic amounts of
      Ph3PAuCl and Cu(OTf)2. A smooth 7-exo-dig cyclization was observed. 

PMID- 25054773
TI  - How do students improve their value-based learning with task experience?
AB  - When learning items that vary in reward, students improve their scores (i.e.,
      earned reward) with task experience. In four experiments, we examined whether
      such improvements arise from better selective encoding of items that would earn
      more (vs. less) reward. Participants studied and recalled words across multiple
      study-test trials. On each trial, 12 words were slated with different values
      (typically from 1 to 12), and participants earned the point value assigned to a
      given word if it was correctly recalled. In all experiments, participants earned
      more points across the first two trials. In Experiment 1, participants either
      self-paced their study or had experimenter-paced study and in Experiment 2, some
      participants were penalised for each second spent during study. Improvements in
      points earned were related to increases in overall recall but not to selective
      encoding. In Experiment 3, some participants were given value-emphasised
      instructions, yet they did not demonstrate selective encoding. In Experiment 4,
      we used a larger range of point values, but selective encoding still did not
      account for the improvement in point scores across lists. These results suggest
      that metacognitively-driven selective encoding is not necessary to observe
      improvements in value-based learning. 

PMID- 25054772
TI  - The structure of RdDddP from Roseobacter denitrificans reveals that DMSP lyases
      in the DddP-family are metalloenzymes.
AB  - Marine microbes degrade dimethylsulfoniopropionate (DMSP), which is produced in
      large quantities by marine algae and plants, with DMSP lyases into acrylate and
      the gas dimethyl sulfide (DMS). Approximately 10% of the DMS vents from the sea
      into the atmosphere and this emission returns sulfur, which arrives in the sea
      through rivers and runoff, back to terrestrial systems via clouds and rain.
      Despite their key role in this sulfur cycle DMSP lyases are poorly understood at
      the molecular level. Here we report the first X-ray crystal structure of the
      putative DMSP lyase RdDddP from Roseobacter denitrificans, which belongs to the
      abundant DddP family. This structure, determined to 2.15 A resolution, shows that
      RdDddP is a homodimeric metalloprotein with a binuclear center of two metal ions
      located 2.7 A apart in the active site of the enzyme. Consistent with the
      crystallographic data, inductively coupled plasma mass spectrometry (ICP-MS) and
      total reflection X-ray fluorescence (TRXF) revealed the bound metal species to be
      primarily iron. A 3D structure guided analysis of environmental DddP lyase
      sequences elucidated the critical residues for metal binding are invariant,
      suggesting all proteins in the DddP family are metalloenzymes.

PMID- 25054774
TI  - MicroPET imaging of CD13 expression using a (64)Cu-labeled dimeric NGR peptide
      based on sarcophagine cage.
AB  - CD13 receptor as a tumor vasculature biomarker has attracted great attention in
      cancer research. Through phage display screening, NGR-containing peptides have
      been characterized as specific ligands binding to CD13 receptor. In this study, a
      (64)Cu-labeled dimeric NGR peptide based on sarcophagine cage was synthesized and
      evaluated for micropositron emission tomography (PET) imaging of CD13 expression
      in vivo. Macrocyclic chelating agent (sarcophagine cage) was conjugated with two
      azide moieties, followed by mixing with an alkyne-containing NGR peptide to
      rapidly provide the Sar-NGR2 peptide by click chemistry. Radiolabeling of Sar
      NGR2 with (64)Cu was achieved in >90% decay-corrected yield with radiochemical
      purity of >99%. The cell uptake study showed that (64)Cu-Sar-NGR2 binds to CD13
      positive HT-1080 cells, but not to CD13-negative MCF-7 cells. MicroPET imaging
      results revealed that (64)Cu-Sar-NGR2 exhibits good tumor uptake in CD13-positive
      HT-1080 xenografts and significantly lower tumor uptake in CD13-negative MCF-7
      xenografts. The CD13-specific binding of (64)Cu-Sar-NGR2 was further verified by
      significant reduction of tumor uptake in HT-1080 tumor xenografts with
      coinjection of a nonradiolabeled NGR peptide. The biodistribution results
      demonstrated good tumor/muscle ratio (8.28 +/- 0.37) of (64)Cu-Sar-NGR2 at 24 h
      pi in HT-1080 tumor xenografts, which is in agreement with the quantitative
      analysis of microPET imaging. In conclusion, sarcophagine cage has been
      successfully applied to the construction of a (64)Cu-labeled dimeric NGR
      containing peptide. In vitro and in vivo studies demonstrated that (64)Cu-Sar
      NGR2 is a promising PET probe for imaging CD13 expression in living mice. 

PMID- 25054776
TI  - The role of adenosine receptors A2A and A2B signaling in renal fibrosis.
AB  - Renal fibrosis, the key histopathological lesion in the development and
      progression of chronic kidney disease (CKD), has been the focus of much research
      in recent decades. The growing burden of CKD in both developed and developing
      nations highlights a need for novel therapies to halt the progression of renal
      disease. Insights into the pathogenesis of renal fibrosis and the key cellular
      and molecular mediators have been critical in the process of identifying
      potential targets of therapy. Adenosine signaling is an innate biological
      autocrine and paracrine cellular signaling pathway involving several key
      mediators: ectonucleotidases, adenosine, and adenosine receptors. Short-term
      activation of the adenosine A2A and A2B receptors decreases inflammation, which
      precedes renal fibrosis. However, in conditions of persistent, excessive
      adenosine exposure, such as in patients born with adenosine deaminase (ADA)
      deficiency, adenosine signaling via A2B receptor promotes renal fibrosis, as seen
      in chronic inflammation. This review will describe the increasingly recognized
      complex role of adenosine signaling in the development of renal fibrosis. We will
      speculate how the knowledge gained may be employed in the search for more
      effective therapies based on these complex signaling pathways. 

PMID- 25054775
TI  - A multicenter randomized trial indicates initial prednisolone treatment for
      childhood nephrotic syndrome for two months is not inferior to six-month
      treatment.
AB  - In this multicenter, open-label, randomized controlled trial, we determined
      whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was
      inferior or not to 6-month therapy despite significantly less steroid exposure.
      The primary end point was time from start of initial treatment to start of
      frequently relapsing nephrotic syndrome. The pre-specified non-inferiority margin
      was a hazard ratio of 1.3 with one-sided significance of 5%. We randomly assigned
      255 children with an initial episode of steroid-sensitive nephrotic syndrome to
      either 2 - or 6-month treatment of which 246 were eligible for final analysis.
      The total prednisolone exposure counted both initial and relapse prednisolone
      treatment administered over 24 months. Median follow-up in months was 36.7 in the
      2-month and 38.2 in the 6-month treatment group. Time to frequent relaps was
      similar in both groups; however, the median was reached only in the 6-month group
      (799 days). The hazard ratio was 0.86 (90% confidence interval, 0.64-1.16) and
      met the non-inferior margin. Time to first relapse was also similar in both
      groups: median day 242 (2-month) and 243 (6-month). Frequency and severity of
      adverse events were similar in both groups. Most adverse events were transient
      and occurred during initial or relapse therapy. Thus, 2 months of initial
      prednisolone therapy for steroid-sensitive nephrotic syndrome, despite less
      prednisolone exposure, is not inferior to 6 months of initial therapy in terms of
      time to onset of frequently relapsing nephrotic syndrome. 

PMID- 25054777
TI  - APOL1 associations with nephropathy, atherosclerosis, and all-cause mortality in
      African Americans with type 2 diabetes.
AB  - Albuminuria and reduced estimated glomerular filtration rate (eGFR) associate
      with two apolipoprotein L1 gene (APOL1) variants in nondiabetic African Americans
      (AAs). Whether APOL1 associates with subclinical atherosclerosis and survival
      remains unclear. To determine this, 717 African American-Diabetes Heart Study
      participants underwent computed tomography to determine coronary artery-, carotid
      artery-, and aorta-calcified atherosclerotic plaque mass scores in addition to
      the urine albumin:creatinine ratio (UACR), eGFR, and C-reactive protein (CRP).
      Associations between mass scores and APOL1 were assessed adjusting for age,
      gender, African ancestry, body mass index (BMI), hemoglobin A1c, smoking,
      hypertension, use of statins and angiotensin-converting enzyme inhibitors,
      albuminuria, and eGFR. Participants were 58.9% female with mean age 56.5 years,
      eGFR 89.5 ml/min per 1.73 m(2), UACR 169.6 mg/g, and coronary artery-, carotid
      artery-, and aorta-calcified plaque mass scores of 610, 171, and 5378,
      respectively. In fully adjusted models, APOL1 risk variants were significantly
      associated with lower levels of carotid artery-calcified plaque (beta=-0.42, s.e.
      0.18; dominant model) and marginally lower coronary artery plaque (beta=-0.36,
      s.e. 0.21; dominant model), but not with aorta-calcified plaque, CRP, UACR, or
      eGFR. By the end of a mean follow-up of 5.0 years, 89 participants had died.
      APOL1 nephropathy risk variants were significantly associated with improved
      survival (hazard ratio 0.67 for one copy; 0.44 for two copies). Thus, APOL1
      nephropathy variants associate with lower levels of subclinical atherosclerosis
      and reduced risk of death in AAs with type 2 diabetes mellitus. 

PMID- 25054779
TI  - Towards intelligent bioreactor systems: triggering the release and mixing of
      compounds based on DNA-functionalized hybrid hydrogel.
AB  - We have designed and synthesized an intelligent mesoporous silica nanoparticle
      DNA hydrogel bioreactor system that can be controlled by external stimuli. The
      system allowed the simultaneous incorporation of multiple components, and the
      separation between the components can be destroyed by a structural change of the
      DNA to initiate a reaction. 

PMID- 25054778
TI  - A closer look at rituximab induction on HLA antibody rebound following HLA
      incompatible kidney transplantation.
AB  - Rituximab has been used to increase the efficacy of desensitization protocols for
      human leukocyte antigen (HLA)-incompatible kidney transplantation; however,
      controlled comparisons have not been reported. Here we examined 256 post
      transplant HLA antibody levels in 25 recipients desensitized with and 25 without
      rituximab induction, to determine the impact of B-cell depletion. We found
      significantly less HLA antibody rebound in the rituximab-treated patients (7% of
      donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control
      cohort desensitized and transplanted without rituximab (32% DSAs and 55% non
      DSAs). The magnitude of the increase was significantly larger among patients who
      did not receive rituximab. Interestingly, in rituximab-treated patients, of the
      39 HLA antibodies that increased post transplant, 34 were specific for HLA
      mismatches present in previous allografts or pregnancies, implying limited
      efficacy in memory B-cell depletion. Compared with controls, rituximab-treated
      patients had a significantly greater mean reduction in DSA (-2505 vs. -292 mean
      fluorescence intensity), but a similar rate of DSA persistence (52% in rituximab
      treated-and 40% in non-treated recipients). Thus, rituximab induction in HLA
      incompatible recipients reduced the incidence and magnitude of HLA antibody
      rebound, but did not affect DSA elimination, antibody-mediated rejection, or 5
      year allograft survival when compared with recipients desensitized and
      transplanted without rituximab. 

PMID- 25054780
TI  - Nanoscale morphological and chemical changes of high voltage lithium-manganese
      rich NMC composite cathodes with cycling.
AB  - Understanding the evolution of chemical composition and morphology of battery
      materials during electrochemical cycling is fundamental to extending battery
      cycle life and ensuring safety. This is particularly true for the much debated
      high energy density (high voltage) lithium-manganese rich cathode material of
      composition Li(1 + x)M(1 - x)O2 (M = Mn, Co, Ni). In this study we combine full
      field transmission X-ray microscopy (TXM) with X-ray absorption near edge
      structure (XANES) to spatially resolve changes in chemical phase, oxidation
      state, and morphology within a high voltage cathode having nominal composition
      Li1.2Mn0.525Ni0.175Co0.1O2. Nanoscale microscopy with chemical/elemental
      sensitivity provides direct quantitative visualization of the cathode, and
      insights into failure. Single-pixel (~ 30 nm) TXM XANES revealed changes in Mn
      chemistry with cycling, possibly to a spinel conformation and likely including
      some Mn(II), starting at the particle surface and proceeding inward.
      Morphological analysis of the particles revealed, with high resolution and
      statistical sampling, that the majority of particles adopted nonspherical shapes
      after 200 cycles. Multiple-energy tomography showed a more homogeneous
      association of transition metals in the pristine particle, which segregate
      significantly with cycling. Depletion of transition metals at the cathode surface
      occurs after just one cycle, likely driven by electrochemical reactions at the
      surface.

PMID- 25054781
TI  - Prevalence, distribution, and diversity of Escherichia coli, Staphylococcus
      aureus, and Salmonella in kiwifruit orchards and processing plants.
AB  - The aim of the study was to investigate the prevalence, distribution, and
      diversity of three foodborne bacteria in kiwifruit orchards and processing
      plants. Fourteen kiwifruit orchards and two processing plants in Shaanxi province
      were visited for sampling in 2012. Fruit samples and environmental samples in
      orchards and plants were taken for isolation of Escherichia coli, Staphylococcus
      aureus, and Salmonella. All isolates were characterized by antimicrobial
      susceptibility testing and detection of virulence genes. Selected isolates were
      further examined by pulsed-field gel electrophoresis (PFGE) analysis. In total,
      160 E. coli isolates and 14 S. aureus isolates were recovered from 407 samples
      from orchards and plants, while no Salmonella was recovered. E. coli isolates
      displayed resistance most frequently to streptomycin (65.6%), and S. aureus
      isolates displayed resistance most frequently to erythromycin (21.4%). Three E.
      coli isolates (1.9%) were positive for stx2 and two S. aureus isolates (14.3%)
      were positive for both seb and seh. Seventy-seven E. coli isolates and 14 S.
      aureus isolates were analyzed by PFGE. PFGE results showed that both E. coli and
      S. aureus isolates were diverse, and blades for slicing during the processing
      could be an important contamination source. This study could provide useful
      information for kiwifruit growers and industry to establish proper management
      practices that help minimize the chance of microbial contamination from farm to
      table.

PMID- 25054782
TI  - Development of trichodysplasia spinulosa: case report of a patient with Gorlin
      syndrome treated with vismodegib.

PMID- 25054783
TI  - Binding modes of two scorpion toxins to the voltage-gated potassium channel kv1.3
      revealed from molecular dynamics.
AB  - Molecular dynamics (MD) simulations are used to examine the binding modes of two
      scorpion toxins, margatoxin (MgTx) and hongotoxin (HgTx), to the voltage gated K+
      channel, Kv1.3. Using steered MD simulations, we insert either Lys28 or Lys35 of
      the toxins into the selectivity filter of the channel. The MgTx-Kv1.3 complex is
      stable when the side chain of Lys35 from the toxin occludes the channel filter,
      suggesting that Lys35 is the pore-blocking residue for Kv1.3. In this complex,
      Lys28 of the toxin forms one additional salt bridge with Asp449 just outside the
      filter of the channel. On the other hand, HgTx forms a stable complex with Kv1.3
      when the side chain of Lys28 but not Lys35 protrudes into the filter of the
      channel. A survey of all the possible favorable binding modes of HgTx-Kv1.3 is
      carried out by rotating the toxin at 3 degrees  intervals around the channel axis
      while the position of HgTx-Lys28 relative to the filter is maintained. We
      identify two possible favorable binding modes: HgTx-Arg24 can interact with
      either Asp433 or Glu420 on the vestibular wall of the channel. The dissociation
      constants calculated from the two binding modes of HgTx-Kv1.3 differ by
      approximately 20 fold, suggesting that the two modes are of similar energetics. 

PMID- 25054784
TI  - The combined repetitive oligopeptides of clostridium difficile toxin A counteract
      premature cleavage of the glucosyl-transferase domain by stabilizing protein
      conformation.
AB  - Toxin A (TcdA) and B (TcdB) from Clostridium difficile enter host cells by
      receptor-mediated endocytosis. A prerequisite for proper toxin action is the
      intracellular release of the glucosyltransferase domain by an inherent cysteine
      protease, which is allosterically activated by inositol hexaphosphate (IP6). We
      found that in in vitro assays, the C-terminally-truncated TcdA1-1065 was more
      efficient at IP6-induced cleavage compared with full-length TcdA. We hypothesized
      that the C-terminally-located combined repetitive oligopeptides (CROPs) interact
      with the N-terminal part of the toxin, thereby preventing autoproteolysis.
      Glutathione-S-transferase (GST) pull-down assays and microscale thermophoresis
      confirmed binding between the CROPs and the glucosyltransferase (TcdA1-542) or
      intermediate (TcdA1102-1847) domain of TcdA, respectively. This interaction
      between the N- and C-terminus was not found for TcdB. Functional assays revealed
      that TcdB was more susceptible to inactivation by extracellular IP6-induced
      cleavage. In vitro autoprocessing and inactivation of TcdA, however,
      significantly increased, either by acidification of the surrounding milieu or
      following exchange of its CROP domain by the homologous CROP domain of TcdB.
      Thus, TcdA CROPs contribute to the stabilization and protection of toxin
      conformation in addition to function as the main receptor binding domain. 

PMID- 25054786
TI  - Two tattoos.

PMID- 25054787
TI  - Clinical doctorates for PAs: future trend...or unneeded expense?

PMID- 25054788
TI  - What caused this dark spot on the patient's back?

PMID- 25054790
TI  - A 59-year-old man with acute onset of paralysis.
AB  - Botulism is a neuroparalytic illness resulting from the action of a potent toxin
      produced by the organism Clostridium botulinum. It can present with a classic
      triad of clear mentation, bulbar palsy and symmetric descending paralysis.
      Treatment is symptomatic and includes a botulinum antitoxin. 

PMID- 25054791
TI  - Congenital heart disease: transitioning from pediatric to adult cardiology care.
AB  - Medical and surgical advances are prolonging the lives of children with
      congenital heart disease (CHD), who are now living into adulthood. Physician
      assistants are well-positioned to play an integral role in supporting the
      transition of patients with CHD from pediatric to adult medical care, thereby
      reducing patients' risk of adverse outcomes. 

PMID- 25054792
TI  - Forecasting the effect of physician assistants in a pediatric ED.
AB  - BACKGROUND: Most pediatric ED visits are for nonemergent problems. Physician
      assistants are well trained to manage these patients; however, their effect on
      patient flow in a pediatric ED is unknown. OBJECTIVES: To compare the effect on
      key pediatric ED efficiency indicators of extending physician coverage versus
      adding PAs with equivalent incremental costs. METHODS: We used discrete event
      simulation modeling to compare the effect of additional physician coverage versus
      adding PAs on wait time, length of stay (LOS), and patients leaving without being
      seen. RESULTS: Simulation of extended physician coverage reduced wait times, LOS,
      and rates of leaving without being seen across acuity levels. Adding PAs reduced
      wait times and LOS for high-acuity visits, and slightly increased the LOS for low
      acuity visits. CONCLUSIONS: With restricted autonomy, PAs mainly benefitted the
      high-acuity patients. Increasing the level of PA autonomy was critical in
      broadening the effect of PAs to all acuity levels.

PMID- 25054793
TI  - Generalized anxiety disorder.

PMID- 25054794
TI  - Staying up to date with the JNC 8 hypertension guideline.
AB  - The recently released JNC 8 guideline on hypertension management is a major
      departure from previous JNC guidelines in methodology, focus, and content. This
      article reviews the design and content of the new guideline as well as its
      similarities and differences from JNC 7 and other recently published hypertension
      guidelines. 

PMID- 25054796
TI  - Abdominal pain after a motor vehicle accident.

PMID- 25054797
TI  - Selling yourself in primary care.

PMID- 25054798
TI  - Earliest cranio-encephalic trauma from the Levantine Middle Palaeolithic: 3D
      reappraisal of the Qafzeh 11 skull, consequences of pediatric brain damage on
      individual life condition and social care.
AB  - The Qafzeh site (Lower Galilee, Israel) has yielded the largest Levantine hominin
      collection from Middle Palaeolithic layers which were dated to circa 90-100 kyrs
      BP or to marine isotope stage 5b-c. Within the hominin sample, Qafzeh 11, circa
      12-13 yrs old at death, presents a skull lesion previously attributed to a healed
      trauma. Three dimensional imaging methods allowed us to better explore this
      lesion which appeared as being a frontal bone depressed fracture, associated with
      brain damage. Furthermore the endocranial volume, smaller than expected for
      dental age, supports the hypothesis of a growth delay due to traumatic brain
      injury. This trauma did not affect the typical human brain morphology pattern of
      the right frontal and left occipital petalia. It is highly probable that this
      young individual suffered from personality and neurological troubles directly
      related to focal cerebral damage. Interestingly this young individual benefited
      of a unique funerary practice among the south-western Asian burials dated to
      Middle Palaeolithic. 

PMID- 25054799
TI  - SSCC TD: a serial and simultaneous configural-cue compound stimuli representation
      for temporal difference learning.
AB  - This paper presents a novel representational framework for the Temporal
      Difference (TD) model of learning, which allows the computation of configural
      stimuli--cumulative compounds of stimuli that generate perceptual emergents known
      as configural cues. This Simultaneous and Serial Configural-cue Compound Stimuli
      Temporal Difference model (SSCC TD) can model both simultaneous and serial
      stimulus compounds, as well as compounds including the experimental context. This
      modification significantly broadens the range of phenomena which the TD paradigm
      can explain, and allows it to predict phenomena which traditional TD solutions
      cannot, particularly effects that depend on compound stimuli functioning as a
      whole, such as pattern learning and serial structural discriminations, and
      context-related effects.

PMID- 25054800
TI  - Jealousy in dogs.
AB  - It is commonly assumed that jealousy is unique to humans, partially because of
      the complex cognitions often involved in this emotion. However, from a functional
      perspective, one might expect that an emotion that evolved to protect social
      bonds from interlopers might exist in other social species, particularly one as
      cognitively sophisticated as the dog. The current experiment adapted a paradigm
      from human infant studies to examine jealousy in domestic dogs. We found that
      dogs exhibited significantly more jealous behaviors (e.g., snapping, getting
      between the owner and object, pushing/touching the object/owner) when their
      owners displayed affectionate behaviors towards what appeared to be another dog
      as compared to nonsocial objects. These results lend support to the hypothesis
      that jealousy has some "primordial" form that exists in human infants and in at
      least one other social species besides humans. 

PMID- 25054801
TI  - Nucleophilic or electrophilic interactions of C2 with HX systems (X = F, Cl, Br).
AB  - Highly correlated ab initio wave functions within the MRCI approach are used in a
      comparative study of the interactions between C2 and the three hydrogen halides
      HX (X = F, Cl, Br). Test calculations are also presented using the UCCSD(T)-F12
      approach. The asymptotic regions are investigated for different relative
      orientations of the two moieties. It is shown that the three systems C2 + HX are
      bound, for intermolecular distances close to 3 A, through nucleophilic
      interactions between C2 and HX for approaches perpendicular to the C-C axis, with
      decreasing interaction energies from HF to HBr. For HX approaching C2 along its
      axis, the interactions, governed by the electrophilic character of C2 are
      decreasing from HBr to HF. Even though the reactions toward the molecular systems
      HCCX or CCHX are exothermic, activation barriers (0.58 eV and more) are
      calculated at short distances, preventing the direct reactions toward the
      corresponding tetra-atomic systems. 

PMID- 25054802
TI  - The metagenomic telescope.
AB  - Next generation sequencing technologies led to the discovery of numerous new
      microbe species in diverse environmental samples. Some of the new species contain
      genes never encountered before. Some of these genes encode proteins with novel
      functions, and some of these genes encode proteins that perform some well-known
      function in a novel way. A tool, named the Metagenomic Telescope, is described
      here that applies artificial intelligence methods, and seems to be capable of
      identifying new protein functions even in the well-studied model organisms. As a
      proof-of-principle demonstration of the Metagenomic Telescope, we considered DNA
      repair enzymes in the present work. First we identified proteins in DNA repair in
      well-known organisms (i.e., proteins in base excision repair, nucleotide excision
      repair, mismatch repair and DNA break repair); next we applied multiple
      alignments and then built hidden Markov profiles for each protein separately,
      across well-researched organisms; next, using public depositories of metagenomes,
      originating from extreme environments, we identified DNA repair genes in the
      samples. While the phylogenetic classification of the metagenomic samples are not
      typically available, we hypothesized that some very special DNA repair strategies
      need to be applied in bacteria and Archaea living in those extreme circumstances.
      It is a difficult task to evaluate the results obtained from mostly unknown
      species; therefore we applied again the hidden Markov profiling: for the
      identified DNA repair genes in the extreme metagenomes, we prepared new hidden
      Markov profiles (for each genes separately, subsequent to a cluster analysis);
      and we searched for similarities to those profiles in model organisms. We have
      found well known DNA repair proteins, numerous proteins with unknown functions,
      and also proteins with known, but different functions in the model organisms. 

PMID- 25054804
TI  - An evaluation of the validity of the animal models of Kawasaki disease
      vasculopathy.

PMID- 25054803
TI  - Medusa: a novel gene drive system for confined suppression of insect populations.
AB  - Gene drive systems provide novel opportunities for insect population suppression
      by driving genes that confer a fitness cost into pest or disease vector
      populations; however regulatory issues arise when genes are capable of spreading
      across international borders. Gene drive systems displaying threshold properties
      provide a solution since they can be confined to local populations and eliminated
      through dilution with wild-types. We propose a novel, threshold-dependent gene
      drive system, Medusa, capable of inducing a local and reversible population
      crash. Medusa consists of four components--two on the X chromosome, and two on
      the Y chromosome. A maternally-expressed, X-linked toxin and a zygotically
      expressed, Y-linked antidote results in suppression of the female population and
      selection for the presence of the transgene-bearing Y because only male offspring
      of Medusa-bearing females are protected from the effects of the toxin. At the
      same time, the combination of a zygotically-expressed, Y-linked toxin and a
      zygotically-expressed, X-linked antidote selects for the transgene-bearing X in
      the presence of the transgene-bearing Y. Together these chromosomes create a
      balanced lethal system that spreads while selecting against females when present
      above a certain threshold frequency. Simple population dynamic models show that
      an all-male release of Medusa males, carried out over six generations, is
      expected to induce a population crash within 12 generations for modest release
      sizes on the order of the wild population size. Re-invasion of non-transgenic
      insects into a suppressed population can result in a population rebound; however
      this can be prevented through regular releases of modest numbers of Medusa males.
      Finally, we outline how Medusa could be engineered with currently available
      molecular tools.

PMID- 25054805
TI  - Final opportunity to rehabilitate an urban river as a water source for Mexico
      City.
AB  - The aim of this study was to evaluate the amount and quality of water in the
      Magdalena-Eslava river system and to propose alternatives for sustainable water
      use. The system is the last urban river in the vicinity of Mexico City that
      supplies surface water to the urban area. Historical flow data were analyzed
      (1973-2010), along with the physicochemical and bacteriological attributes,
      documenting the evolution of these variables over the course of five years (2008
      2012) in both dry and rainy seasons. The analyses show that the flow regime has
      been significantly altered. The physicochemical variables show significant
      differences between the natural area, where the river originates, and the urban
      area, where the river receives untreated wastewater. Nutrient and conductivity
      concentrations in the river were equivalent to domestic wastewater. Fecal
      pollution indicators and various pathogens were present in elevated densities,
      demonstrating a threat to the population living near the river. Estimates of the
      value of the water lost as a result of mixing clean and contaminated water are
      presented. This urban river should be rehabilitated as a sustainability practice,
      and if possible, these efforts should be replicated in other areas. Because of
      the public health issues and in view of the population exposure where the river
      flows through the city, the river should be improved aesthetically and should be
      treated to allow its ecosystem services to recover. This river represents an
      iconic case for Mexico City because it connects the natural and urban areas in a
      socio-ecological system that can potentially provide clean water for human
      consumption. Contaminated water could be treated and reused for irrigation in one
      of the green areas of the city. Wastewater treatment plants and the operation of
      the existing purification plants are urgent priorities that could lead to better,
      more sustainable water use practices in Mexico City. 

PMID- 25054806
TI  - Estimating species richness and modelling habitat preferences of tropical forest
      mammals from camera trap data.
AB  - Medium-to-large mammals within tropical forests represent a rich and functionally
      diversified component of this biome; however, they continue to be threatened by
      hunting and habitat loss. Assessing these communities implies studying species'
      richness and composition, and determining a state variable of species abundance
      in order to infer changes in species distribution and habitat associations. The
      Tropical Ecology, Assessment and Monitoring (TEAM) network fills a chronic gap in
      standardized data collection by implementing a systematic monitoring framework of
      biodiversity, including mammal communities, across several sites. In this study,
      we used TEAM camera trap data collected in the Udzungwa Mountains of Tanzania, an
      area of exceptional importance for mammal diversity, to propose an example of a
      baseline assessment of species' occupancy. We used 60 camera trap locations and
      cumulated 1,818 camera days in 2009. Sampling yielded 10,647 images of 26 species
      of mammals. We estimated that a minimum of 32 species are in fact present,
      matching available knowledge from other sources. Estimated species richness at
      camera sites did not vary with a suite of habitat covariates derived from remote
      sensing, however the detection probability varied with functional guilds, with
      herbivores being more detectable than other guilds. Species-specific occupancy
      modelling revealed novel ecological knowledge for the 11 most detected species,
      highlighting patterns such as 'montane forest dwellers', e.g. the endemic Sanje
      mangabey (Cercocebus sanjei), and 'lowland forest dwellers', e.g. suni antelope
      (Neotragus moschatus). Our results show that the analysis of camera trap data
      with account for imperfect detection can provide a solid ecological assessment of
      mammal communities that can be systematically replicated across sites.

PMID- 25054808
TI  - The "moral career" of perinatally HIV-infected children: revisiting Goffman's
      concept.
AB  - HIV-infected children usually live in vulnerable situations, experiencing
      discrimination and stigma commonly felt by other people living with HIV/AIDS. The
      present study aims to analyse primary socialisation of HIV-infected children and
      adolescents recruited from a public health service in Rio de Janeiro (Brazil) as
      a social process that shapes a new generation of stigmatised and vulnerable
      persons. Research was informed by an interactionist perspective, focusing on key
      aspects of HIV-infected children and adolescents life histories under the
      conceptual frame of Erving Goffman's theories regarding "moral careers". Goffman
      defines the making of a moral career as the process through which a person learns
      that she/he possesses a particular attribute, which may lead her/him to be
      discredited by members of the surrounding society. We have identified aspects of
      life histories of HIV-vertically infected children and adolescents for each
      aspect of "moral career" as described by Goffman, relating them to as family
      structure, the experience of living HIV within the family, and the position and
      family role of a given subject. The patterns of "moral career" proposed by
      Goffman in 1963 were useful in identifying components of HIV-related stigma among
      children and adolescents. These include gender and social disadvantages,
      difficulty in coping with a child with a potentially severe disease, orphanhood,
      abandonment, adoption and disclosure of one's HIV serostatus. Primary
      socialisation of HIV-infected children and adolescents is a key piece of the
      complex HIV/AIDS-labelling process that could be targeted by interventions aiming
      to decrease stigma and marginalisation. Health care workers and stakeholders
      should be committed to ensuring education and guaranteeing the legal rights of
      this specific population, including the continuous provision of quality health
      care, full access to school and support to full disclosure of HIV diagnosis.

PMID- 25054807
TI  - Interaction with epithelial cells modifies airway macrophage response to ozone.
AB  - The initial innate immune response to ozone (O3) in the lung is orchestrated by
      structural cells, such as epithelial cells, and resident immune cells, such as
      airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to
      investigate how epithelial cell-derived signals affect Mac response to O3. Macs
      from the bronchoalveolar lavage (BAL) of healthy volunteers were cocultured with
      the human bronchial epithelial (16HBE) or alveolar (A549) epithelial cell lines.
      Cocultures, Mac monocultures, and epithelial cell monocultures were exposed to O3
      or air, and Mac immunophenotype, phagocytosis, and cytotoxicity were assessed.
      Quantities of hyaluronic acid (HA) and IL-8 were compared across cultures and in
      BAL fluid from healthy volunteers exposed to O3 or air for in vivo confirmation.
      We show that Macs in coculture had increased markers of alternative activation,
      enhanced cytotoxicity, and reduced phagocytosis compared with Macs in monoculture
      that differed based on coculture with A549 or 16HBE. Production of HA by
      epithelial cell monocultures was not affected by O3, but quantities of HA in the
      in vitro coculture and BAL fluid from volunteers exposed in vivo were increased
      with O3 exposure, indicating that O3 exposure impairs Mac regulation of HA.
      Together, we show epithelial cell-Mac coculture models that have many
      similarities to the in vivo responses to O3, and demonstrate that epithelial cell
      derived signals are important determinants of Mac immunophenotype and response to
      O3. 

PMID- 25054809
TI  - Retroperitoneoscopic donor nephrectomy with multiple renal arteries does not
      affect graft survival and ureteral complications.
AB  - BACKGROUND: Outcomes of retroperitoneoscopic procurement of living kidneys with
      multiple renal arteries (MRA) in the recipients are largely unknown. Our aim is
      to access the effect of kidney allografts with MRA on donor and recipient
      outcomes after pure retroperitoneoscopic live donor nephrectomy (RPLDN). METHODS:
      From July 2001 to August 2010, 533 patients underwent live donor kidney
      transplants with allografts procured by RPLDN at our center. Of these 533
      transplants, 406, 105, and 22 patients had one, two, and three renal arteries,
      respectively. We compared the retrospectively collected clinical data of each
      donor with MRA and the recipient using those with single renal artery as
      controls. RESULTS: Significant differences were found among the one-renal artery
      and three-renal artery groups regarding operative time, estimated blood loss,
      warm and cold ischemic time, and incidence of slow graft function (SGF). However,
      there was no significant difference regarding patient and graft survival among
      the three groups. Major complications, such as open conversion, bleeding, and
      blood transfusion, were not found in patients with MRA. Five ureteral
      complications occurred. Of these, there was one patient with MRA. In univariate
      analysis, MRA patients had a risk factor of developing SGF (P=0.005) but not
      ureteral complications following RPLDN. CONCLUSION: Kidneys with MRA after RPLDN
      increase the risk of SGF in recipients. However, they provide similar outcomes as
      to long-term graft survival and complications compared with those of single renal
      artery. Renal artery multiplicity should not be a contraindication for live
      kidney donation and may not increase the risk of ureteral complications.

PMID- 25054810
TI  - Determining the muscle voluntary activation characteristics in children: a
      methodological challenge. Commentary on "Child-adult differences in muscle
      activation--a review".

PMID- 25054811
TI  - Synthesis of P1'-functionalized macrocyclic transition-state mimicking HIV-1
      protease inhibitors encompassing a tertiary alcohol.
AB  - Seven novel tertiary alcohol containing linear HIV-1 protease inhibitors (PIs),
      decorated at the para position of the benzyl group in the P1' side with
      (hetero)aromatic moieties, were synthesized and biologically evaluated. To study
      the inhibition and antiviral activity effect of P1-P3 macrocyclization, 14- and
      15-membered macrocyclic PIs were prepared by ring-closing metathesis of the
      corresponding linear PIs. The macrocycles were more active than the linear
      precursors and compound 10f, with a 2-thiazolyl group in the P1' position, was
      the most potent PI of this new series (Ki 2.2 nM, EC50 0.2 MUM). Co-crystallized
      complexes of both linear and macrocyclic PIs with the HIV-1 protease enzyme were
      prepared and analyzed. 

PMID- 25054812
TI  - Integrin-targeted zwitterionic polymeric nanoparticles with acid-induced
      disassembly property for enhanced drug accumulation and release in tumor.
AB  - Reasonably structural design of nanoparticles (NPs) to combine functions of
      prolonged systemic circulation, enhanced tumor targeting and specific
      intracellular drug release is crucial for antitumor drug delivery. Combining
      advantages of Arg-Gly-Asp (RGD) for active tumor targeting, zwitterionic
      polycarboxybetaine methacrylate (PCB) for prolonged systemic circulation, poly(2
      (diisopropylamino) ethyl methacrylate) (PDPA) for acid-triggered intracellular
      release, novel RGD-PCB-b-PDPA (RGD-PCD) block copolymers were prepared via
      reversible addition-fragmentation chain transfer (RAFT) polymerization and
      followed by functionalization with RGD. Doxorubicine (DOX) was encapsulated
      within the RGD-PCD NPs as model medicine (RGD-PCD/DOX NPs). With ultra pH
      sensitivity of PDPA, the drug release was restrained at pH 7.4 for only 24%
      within 36 h, which was increased to 60% at pH 6.0 within 24 h, and released more
      rapidly at pH 5.0 for 100% within 5 h, indicating that the RGD-PCD/DOX NPs were
      able to turn drug release "off" at neutral pH (e.g., systemic circulation)
      whereas "on" under acidic conditions (e.g., inside endo/lysosomes). Furthermore,
      the results of fluorescence microscopy and flow cytometry analysis demonstrated
      improved internalization of RGD-PCD/DOX NPs in HepG2 cells via integrin-mediated
      endocytosis with rapid DOX release intracellularly. Consequently, the RGD-PCD/DOX
      NPs showed considerable cytotoxicity against HepG2 and HeLa cells in comparison
      with free DOX. Importantly, the RGD-PCD/DOX NPs exhibited little protein
      adsorption property with excellent serum stability, which led to prolonged
      systemic circulation and enhanced tumor accumulation in tumor-bearing nude mice.
      Therefore, this multifunctional RGD-PCD NPs, which represented the flexible
      design approach, showed great potential for the development of novel nanocarriers
      in tumor-targeted drug delivery. 

PMID- 25054813
TI  - Cancer stem cells: moving past the controversy.

PMID- 25054814
TI  - The unfolded protein response in glioblastomas: passing the stress test.

PMID- 25054815
TI  - First-line bevacizumab for glioblastoma: what do recent Trail results mean for
      future treatment?

PMID- 25054816
TI  - What is the best way to evaluate clinical target volume for radiotherapy of brain
      tumors?

PMID- 25054819
TI  - Molecular neuro-oncology: a forward-looking perspective.
AB  - Professor Wolfgang Wick speaks to Tess O'Neill, Head of Commissioning: Wolfgang
      Wick is the Chairman of the Department of Neuro-Oncology, Hertie Professor of
      Neuro-Oncology and Director at the National Tumor Center at the University of
      Heidelberg, Germany. He is conducting multicenter Phase III randomized trials for
      the Neuro-Oncology Working Group of the German Cancer Society, the European
      Organisation for Research and Treatment of Cancer as well as a number of
      multicenter trials with the pharmaceutical industry. He is a steering committee
      member of the Neuro-Oncology Working Group and the European Association for Neuro
      oncology as well as chairman of the European Organisation for Research and
      Treatment of Cancer Brain Tumor Group. His main scientific interests include
      migration and invasion of glioma cells, biomarkers and radiosensitization.

PMID- 25054820
TI  - Molecular prognostic factors in glioblastoma: state of the art and future
      challenges.
AB  - Gliomas account for the majority of primary tumors of the CNS, of which
      glioblastoma (GBM) is the most common and malignant, and for which survival is
      very poor. Despite significant inter- and intra-tumor heterogeneity, all patients
      are treated with a standardized therapeutic approach. While some clinical
      features of GBM patients have already been established as classic prognostic
      factors (e.g., patient age at diagnosis and Karnofsky performance status), one of
      the most important research fields in neuro-oncology today is the identification
      of novel molecular determinants of patient survival and tumor response to
      therapy. Here, we aim to review and discuss some of the most relevant and novel
      prognostic biomarkers in adult and pediatric GBM patients that may aid in
      stratifying subgroups of GBMs and rationalizing treatment decisions.

PMID- 25054821
TI  - Emerging methods for disease monitoring in malignant gliomas.
AB  - MRI remains the backbone of measuring disease burden and treatment response in
      individuals with malignant gliomas. Traditional radiographic approaches, however,
      are largely limited to depicting anatomic changes and are not a direct measure of
      disease burden. For example, contrast enhancement is related to blood-brain
      barrier integrity rather than actual tumor size. Without accurate measures of
      disease, common clinical dilemmas include 'pseudo-progression' (e.g., after
      chemoradiation) or 'pseudo-response' (e.g., with steroid treatment and
      antiangiogenic agents), which can lead to delays in therapy, premature
      discontinuation of successful treatments and to unnecessary surgical procedures.
      This overview focuses on novel, minimally invasive approaches in the area of
      imaging and blood-based biomarkers that aim to more accurately determine disease
      status and response to treatment in malignant brain tumors.

PMID- 25054822
TI  - Aggressive behavior and anaplasia in pleomorphic xanthoastrocytoma: a plea for a
      revision of the current WHO classification.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm that commonly
      affects children and young adults, and presents with seizures. PXA is typically
      supratentorial with a predilection to the temporal lobe, and often involves the
      cortex and the meninges. PXAs have a favorable prognosis with a 10-year survival
      probability of >70%, and are WHO grade II neoplasms. Recent observations and
      studies demonstrate that PXAs are clinically, histologically and genetically
      distinct. Some PXAs recur and exhibit aggressive clinical behavior. In such
      cases, certain histological and clinical factors could account for the aggressive
      behavior. However, the histological features that predict adverse outcome are
      poorly defined. In the current WHO classification of CNS tumors, there is no
      option for a high-grade PXA, even if the tumor had numerous recurrences and poor
      outcome. In this review, we focus on aggressive clinical behavior and anaplasia
      in PXA, and discuss how our current experience suggests modifications in the
      current WHO classification. We also review recent discoveries on the molecular
      characteristics of PXA that could help us better understand their biological
      behavior.

PMID- 25054823
TI  - Pharmacological interventions to treat or prevent neurocognitive decline after
      brain radiation.
AB  - After surgery, radiation is the most effective treatment for the majority of
      brain tumors in both children and adults. Although improvements in radiotherapy
      delivery and targeting have resulted in reduction in neurologic morbidity,
      radiotherapy is still associated with acute and late toxicities that are
      dependent on a variety of treatment- and patient-specific variables. Variables of
      treatment include radiation dose, fractionation, volume, technique, photons or
      protons, and concomitant or adjuvant chemotherapy. Patient- and tumor-specific
      variables include tumor type, location and patient age. Side effects of treatment
      are also variable and can range from mild fatigue to significant memory
      difficulties and even death. This review will focus on the hypothesized
      mechanisms of cognitive dysfunction after radiation therapy and will discuss
      possible intervention strategies including behavioral and pharmacological
      prevention and treatment.

PMID- 25054825
TI  - The ratchet effect: dramatic and sustained changes in health care utilization
      following admission to hospital with chronic disease.
AB  - OBJECTIVE: To describe the previously unexamined association between admissions
      to hospital with chronic disease and changes in all-cause health service
      utilization over time. RESEARCH DESIGN: A cohort study examining the population
      of Western Australia with hospitalizations for chronic disease from 2002 to 2010.
      A "rolling" clearance period is used to define "cardinal events," that is, a
      disease-specific diagnosis upon hospital admission, where such an event has not
      occurred in the previous 2 years. Changes in the rate of cardinal events
      associated with diagnoses of heart failure, type 2 diabetes, chronic obstructive
      pulmonary disease, cataract with diabetes, asthma, and dialysis are examined.
      Health service utilization (defined as inpatient days or emergency department
      presentations) 6 years preceding and 4 years following such events is presented.
      RESULTS: Cardinal events make up 40%-60% of all chronic disease admissions. A
      previously undescribed ratchet effect following cardinal events specifically
      associated with type 2 diabetes, heart failure, and chronic obstructive pulmonary
      disease is observed. This involves a 2- to 3-fold increase in inpatient days and
      emergency department presentations that are sustained for at least 4 years.
      CONCLUSIONS: Cardinal events represent an important reference point to understand
      the impact of chronic disease on health service utilization. Events that herald
      such a marked transition in health service demand have not been previously
      described.

PMID- 25054826
TI  - The origin and disposition of Medicare observation stays.
AB  - BACKGROUND: Growing use of hospital observation care continues unabated despite
      growing concerns from Medicare beneficiaries, patient advocacy groups, providers,
      and policy makers. Unlike inpatient stays, outpatient observation stays are
      subject to 20% coinsurance and do not count toward the 3-day stay required for
      Medicare coverage of skilled nursing facility (SNF) care. Despite the policy
      relevance, we know little about where patients originate or their discharge
      disposition following observation stays, making it difficult to understand the
      scope of unintended consequences for beneficiaries, particularly those needing
      postacute care in a SNF. OBJECTIVE: To determine Medicare beneficiaries' location
      immediately preceding and following an observation stay. RESEARCH DESIGN: We
      linked 100% Medicare Inpatient and Outpatient claims data with the Minimum Data
      Set for nursing home resident assessments. We then flagged observation stays and
      conducted a descriptive claims-based analysis of where beneficiaries were
      immediately before and after their observation stay. RESULTS: Most patients came
      from (92%) and were discharged to (90%) the community. Of >1 million total
      observation stays in 2009, just 7537 (0.75%) were at risk for high out-of-pocket
      expenses related to postobservation SNF care. Beneficiaries with longer
      observation stays were more likely to be discharged to SNF. CONCLUSIONS: With few
      at risk for being denied Medicare SNF coverage due to observation care, high out
      of-pocket costs resulting from Medicare outpatient coinsurance requirements for
      observation stays seem to be of greater concern than limitations on Medicare
      coverage of postacute care. However, future research should explore how
      observation stay policy might decrease appropriate SNF use.

PMID- 25054827
TI  - Enhancing magnetic resonance imaging with contrast agents for ultra-high field
      strengths.
AB  - Contrast agents are diagnostic tools that often complement magnetic resonance
      imaging. At ultra-high field strengths (>=7 T), magnetic resonance imaging is
      capable of generating desirable high signal-to-noise ratios, but clinically
      available contrast agents are less effective at ultra-high field strengths
      relative to lower fields. This gap in effectiveness demands the development of
      contrast agents for ultra-high field strengths. In this minireview, we summarize
      contrast agents reported during the last three years that focused on ultra-high
      field strengths. 

PMID- 25054828
TI  - PIK3CA gene mutations and overexpression: implications for prognostic biomarker
      and therapeutic target in Chinese esophageal squamous cell carcinoma.
AB  - AIMS: To evaluate PIK3CA gene mutations and PIK3CA expression status in Chinese
      esophageal squamous cell carcinoma (ESCC) patients, and their correlation with
      clinicopathological characteristics and clinical outcomes. METHODS: Direct
      sequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA in
      406 Chinese ESCC patients. PIK3CA expression was evaluated using
      immunohistochemistry analysis. The associations of PIK3CA gene mutations and
      PIK3CA expression with clinicopathological characteristics and clinical outcome
      were examined. RESULTS: Thirty somatic point mutations (30/406, 7.4%) were
      identified in exon 9 whereas no mutations were detected in exon 20. PIK3CA
      mutations were not correlated with clinicopathological characteristics or
      clinical outcomes. However in the ESCC patients with family cancer history,
      PIK3CA mutations were independently correlated with worse overall survival
      (multivariate hazard ratio (HR) = 10.493, 95% CI: 2.432-45.267, P = 0.002).
      Compared to normal esophageal tissue, PIK3CA was significantly overexpressed in
      cancer tissue (P<0.001). PIK3CA overexpression was independently associated with
      higher risk of local recurrence (multivariate HR  = 1.435, 95% CI: 1.040-1.979, P
      = 0.028). In female ESCC patients, PIK3CA overexpression was independently
      correlated with worse overall survival (multivariate HR  = 2.341, 95% CI: 1.073
      5.108, P = 0.033). CONCLUSIONS: Our results suggest PIK3CA gene mutation and
      overexpression could act as biomarkers for individualized molecular targeted
      therapy for Chinese ESCC patients.

PMID- 25054829
TI  - Spatial and temporal occurrence of blue whales off the U.S. West Coast, with
      implications for management.
AB  - Mortality and injuries caused by ship strikes in U.S. waters are a cause of
      concern for the endangered population of blue whales (Balaenoptera musculus)
      occupying the eastern North Pacific. We sought to determine which areas along the
      U.S. West Coast are most important to blue whales and whether those areas change
      inter-annually. Argos-monitored satellite tags were attached to 171 blue whales
      off California during summer/early fall from 1993 to 2008. We analyzed portions
      of the tracks that occurred within U.S. Exclusive Economic Zone waters and
      defined the 'home range' (HR) and 'core areas' (CAU) as the 90% and 50% fixed
      kernel density distributions, respectively, for each whale. We used the number of
      overlapping individual HRs and CAUs to identify areas of highest use. Individual
      HR and CAU sizes varied dramatically, but without significant inter-annual
      variation despite covering years with El Nino and La Nina conditions. Observed
      within-year differences in HR size may represent different foraging strategies
      for individuals. The main areas of HR and CAU overlap among whales were near
      highly productive, strong upwelling centers that were crossed by commercial
      shipping lanes. Tagged whales generally departed U.S. Exclusive Economic Zone
      waters from mid-October to mid-November, with high variability among individuals.
      One 504-d track allowed HR and CAU comparisons for the same individual across two
      years, showing similar seasonal timing, and strong site fidelity. Our analysis
      showed how satellite-tagged blue whales seasonally used waters off the U.S. West
      Coast, including high-risk areas. We suggest possible modifications to existing
      shipping lanes to reduce the likelihood of collisions with vessels.

PMID- 25054830
TI  - The ethical framing of personalized medicine.
AB  - PURPOSE OF REVIEW: Personalized medicine encompasses the use of biological
      information such as genomics to provide tailored interventions for patients. The
      review explores the ethical, legal, and social issues that have emerged with
      personalized medicine and must be considered because of the complex nature of
      providing individualized care within a clinical setting. RECENT FINDINGS: Recent
      studies found that the use of personalized medicine presents challenges in
      multiple areas: biobanking and informed consent, confidentiality, genetic
      discrimination, return of results, access to treatment, clinical translation,
      direct-to-consumer genetic testing, emerging duties, and knowledge mobilization.
      SUMMARY: Although personalized medicine provides benefits in treating patients in
      a manner that is more suited to their genetic profile, there are challenges that
      must be discussed to ensure the protection and fair treatment of individuals. The
      issues concerning personalized medicine are widespread, and range from individual
      privacy to the stratification and discrimination of sub-populations based on
      ethnicity. These issues have considerable impact on the individual and society. A
      thorough exploration of these ethical issues may identify novel challenges as
      well as potential avenues for resolution.

PMID- 25054831
TI  - Topical immunomodulators in the management of allergic eye diseases.
AB  - PURPOSE OF REVIEW: Allergic eye diseases comprise a spectrum of diseases, with
      each condition being characterized by a complex immunopathology. The more severe
      and chronic conditions, such as vernal keratoconjunctivitis and atopic
      keratoconjunctivitis, involve predominantly mast cells and eosinophils, while
      also being associated with a preponderance of T cells. Treatment with topical
      antihistamines or mast cell stabilizers is often unsatisfactory, and therapy
      depends on topical corticosteroids. Corticosteroids have significant side-effects
      with long-term use; therefore, they appear to be more appropriate for short-term
      pulse therapy. Immunomodulatory agents can also be used to inhibit T-cell
      activation and show encouraging results among patients with severe allergic eye
      conditions. The present review is an attempt to present a coherent picture of the
      recent investigations of topical immunomodulatory agents' therapy in severe
      allergic eye diseases, especially cyclosporine A and tacrolimus, and their
      mechanisms of action. RECENT FINDINGS: Immunomodulatory agents are commonly
      indicated for the treatment of severe and prolonged allergic conjunctivitis. This
      article reviews the recent studies of these drugs and the development of
      immunomodulatory treatments for severe allergic eye diseases. SUMMARY:
      Cyclosporine A and tacrolimus are currently available for the treatment of severe
      allergic conjunctivitis. These agents have led to improved therapeutic results
      for patients with severe and chronic allergic eye diseases.

PMID- 25054832
TI  - New findings in allergic contact dermatitis.
AB  - PURPOSE OF REVIEW: Contact allergies are complex diseases and an important
      challenge for public health. The purpose of this review is to discuss new
      developments in the field, including epidemiology and molecular mechanisms of
      contact allergy. RECENT FINDINGS: Understanding how contact allergens promote
      allergic reactions is important for preventing the disease. According to the
      latest knowledge, contact allergens are sensed by toll-like receptors and the
      inflammasome, and possibly the activation of these pathways is a trait shared by
      all sensitizing compounds. Allergies to nickel, fragrances and preservatives are
      still frequent, despite regulations aimed at reducing the exposure to potential
      allergens. Significant numbers of people are exposed, likely due to insufficient
      protection. Further, replacement of known sensitizers by new potential allergens,
      and new products and habits, lead to new exposures, and new cases of contact
      allergies are continuously being reported. The proposed European Union
      legislation to label patch test materials as drugs is unnecessary and harmful for
      treatment of patients with dermatitis. SUMMARY: The immune response to contact
      allergens is complex. Research effort is underway to elucidate the various
      mechanisms and to single out potential allergens and their potency. Legislation
      has to focus on protection of consumers and workers, and adapt as our
      understanding of allergic contact dermatitis progresses.

PMID- 25054833
TI  - Immobilization of hydrophilic low molecular-weight molecules in nanoparticles of
      chitosan/poly(sodium 4-styrenesulfonate) assisted by aromatic-aromatic
      interactions.
AB  - The immobilization of the hydrophilic low molecular-weight cationic molecules
      rhodamine 6G, methylene blue, and citidine in nanoparticles composed of two
      opposite charged polyelectrolytes, poly(sodium 4-styrenesulfonate) and chitosan,
      is studied, and the results correlated with their physicochemical properties.
      Nanoparticles containing both polyelectrolytes have been synthesized showing
      hydrodynamic diameters of around 200 nm and tunable zeta potential. It was found
      that the strength of binding of the cationic molecules to the polyanion bearing
      charged aromatic groups poly(sodium 4-styrenesulfonate) by means of short-range
      aromatic-aromatic interactions increases with their hydrophobicity and
      polarizability, as seen by (1)H NMR and UV-vis spectroscopies, and diafiltration.
      Consequently, association efficiencies of 45, 21, and 12% have been found for the
      three molecules, respectively, revealing the different ability of the molecules
      to be immobilized in the nanoparticles. These results provide a proof of concept
      on a new strategy of immobilization of hydrophilic low molecular-weight molecules
      based on aromatic-aromatic interactions between polyelectrolytes and their
      aromatic counterions. 

PMID- 25054834
TI  - How often do they have sex? A comparative analysis of the population structure of
      seven eukaryotic microbial pathogens.
AB  - The model of predominant clonal evolution (PCE) proposed for micropathogens does
      not state that genetic exchange is totally absent, but rather, that it is too
      rare to break the prevalent PCE pattern. However, the actual impact of this
      "residual" genetic exchange should be evaluated. Multilocus Sequence Typing
      (MLST) is an excellent tool to explore the problem. Here, we compared online
      available MLST datasets for seven eukaryotic microbial pathogens: Trypanosoma
      cruzi, the Fusarium solani complex, Aspergillus fumigatus, Blastocystis subtype
      3, the Leishmania donovani complex, Candida albicans and Candida glabrata. We
      first analyzed phylogenetic relationships among genotypes within each dataset.
      Then, we examined different measures of branch support and incongruence among
      loci as signs of genetic structure and levels of past recombination. The analyses
      allow us to identify three types of genetic structure. The first was
      characterized by trees with well-supported branches and low levels of
      incongruence suggesting well-structured populations and PCE. This was the case
      for the T. cruzi and F. solani datasets. The second genetic structure,
      represented by Blastocystis spp., A. fumigatus and the L. donovani complex
      datasets, showed trees with weakly-supported branches but low levels of
      incongruence among loci, whereby genetic structuration was not clearly defined by
      MLST. Finally, trees showing weakly-supported branches and high levels of
      incongruence among loci were observed for Candida species, suggesting that
      genetic exchange has a higher evolutionary impact in these mainly clonal yeast
      species. Furthermore, simulations showed that MLST may fail to show right
      clustering in population datasets even in the absence of genetic exchange. In
      conclusion, these results make it possible to infer variable impacts of genetic
      exchange in populations of predominantly clonal micro-pathogens. Moreover, our
      results reveal different problems of MLST to determine the genetic structure in
      these organisms that should be considered.

PMID- 25054835
TI  - Biochar impacts soil microbial community composition and nitrogen cycling in an
      acidic soil planted with rape.
AB  - Biochar has been suggested to improve acidic soils and to mitigate greenhouse gas
      emissions. However, little has been done on the role of biochar in ameliorating
      acidified soils induced by overuse of nitrogen fertilizers. In this study, we
      designed a pot trial with an acidic soil (pH 4.48) in a greenhouse to study the
      interconnections between microbial community, soil chemical property changes, and
      N2O emissions after biochar application. The results showed that biochar
      increased plant growth, soil pH, total carbon, total nitrogen, C/N ratio, and
      soil cation exchange capacity. The results of high-throughput sequencing showed
      that biochar application increased alpha-diversity significantly and changed the
      relative abundances of some microbes that are related with carbon and nitrogen
      cycling at the family level. Biochar amendment stimulated both nitrification and
      denitrification processes, while reducing N2O emissions overall. Results of
      redundancy analysis indicated biochar could shift the soil microbial community by
      changing soil chemical properties, which modulate N-cycling processes and soil
      N2O emissions. The significantly increased nosZ transcription suggests that
      biochar decreased soil N2O emissions by enhancing its further reduction to N2. 

PMID- 25054837
TI  - The Cambridge Face Memory Test for Children (CFMT-C): a new tool for measuring
      face recognition skills in childhood.
AB  - Face recognition ability follows a lengthy developmental course, not reaching
      maturity until well into adulthood. Valid and reliable assessments of face
      recognition memory ability are necessary to examine patterns of ability and
      disability in face processing, yet there is a dearth of such assessments for
      children. We modified a well-known test of face memory in adults, the Cambridge
      Face Memory Test (Duchaine & Nakayama, 2006, Neuropsychologia, 44, 576-585), to
      make it developmentally appropriate for children. To establish its utility, we
      administered either the upright or inverted versions of the computerised
      Cambridge Face Memory Test - Children (CFMT-C) to 401 children aged between 5 and
      12 years. Our results show that the CFMT-C is sufficiently sensitive to
      demonstrate age-related gains in the recognition of unfamiliar upright and
      inverted faces, does not suffer from ceiling or floor effects, generates robust
      inversion effects, and is capable of detecting difficulties in face memory in
      children diagnosed with autism. Together, these findings indicate that the CFMT-C
      constitutes a new valid assessment tool for children's face recognition skills.

PMID- 25054836
TI  - Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized
      clinical trial.
AB  - IMPORTANCE: Select cases of intractable obsessive-compulsive disorder (OCD) have
      undergone neurosurgical ablation for more than half a century. However, to our
      knowledge, there have been no randomized clinical trials of such procedures for
      the treatment of any psychiatric disorder. OBJECTIVE: To determine the efficacy
      and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable
      OCD. DESIGN, SETTING, AND PARTICIPANTS: In a double-blind, placebo-controlled,
      randomized clinical trial, 16 patients with intractable OCD were randomized to
      active (n = 8) or sham (n = 8) GVC. Blinding was maintained for 12 months. After
      unblinding, sham-group patients were offered active GVC. INTERVENTIONS: Patients
      randomized to active GVC had 2 distinct isocenters on each side irradiated at the
      ventral border of the anterior limb of the internal capsule. The patients
      randomized to sham GVC received simulated radiosurgery using the same equipment.
      MAIN OUTCOMES AND MEASURES: Scores on the Yale-Brown Obsessive-Compulsive Scale
      (Y-BOCS) and the Clinical Global Impression-Improvement (CGI-I) Scale. Response
      was defined as a 35% or greater reduction in Y-BOCS severity and "improved" or
      "much improved" CGI-I ratings. RESULTS: Three of 8 patients randomized to active
      treatment responded at 12 months, while none of the 8 sham-GVC patients responded
      (absolute risk reduction, 0.375; 95% CI, 0.04-0.71). At 12 months, OCD symptom
      improvement was significantly higher in the active-GVC group than in the sham
      group (Y-BOCS, P = .046; Dimensional Y-BOCS, P = .01). At 54 months, 2 additional
      patients in the active group had become responders. Of the 4 sham-GVC patients
      who later received active GVC, 2 responded by post-GVC month 12. The most serious
      adverse event was an asymptomatic radiation-induced cyst in 1 patient.
      CONCLUSIONS AND RELEVANCE: Gamma ventral capsulotomy benefitted patients with
      otherwise intractable OCD and thus appears to be an alternative to deep-brain
      stimulation in selected cases. Given the risks inherent in any psychiatric
      neurosurgery, such procedures should be conducted at specialized centers. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01004302.

PMID- 25054838
TI  - Identification of hematomas in mild traumatic brain injury using an index of
      quantitative brain electrical activity.
AB  - Rapid identification of traumatic intracranial hematomas following closed head
      injury represents a significant health care need because of the potentially life
      threatening risk they present. This study demonstrates the clinical utility of an
      index of brain electrical activity used to identify intracranial hematomas in
      traumatic brain injury (TBI) presenting to the emergency department (ED). Brain
      electrical activity was recorded from a limited montage located on the forehead
      of 394 closed head injured patients who were referred for CT scans as part of
      their standard ED assessment. A total of 116 of these patients were found to be
      CT positive (CT+), of which 46 patients with traumatic intracranial hematomas
      (CT+) were identified for study. A total of 278 patients were found to be CT
      negative (CT-) and were used as controls. CT scans were subjected to quantitative
      measurements of volume of blood and distance of bleed from recording electrodes
      by blinded independent experts, implementing a validated method for hematoma
      measurement. Using an algorithm based on brain electrical activity developed on a
      large independent cohort of TBI patients and controls (TBI-Index), patients were
      classified as either positive or negative for structural brain injury.
      Sensitivity to hematomas was found to be 95.7% (95% CI = 85.2, 99.5), specificity
      was 43.9% (95% CI = 38.0, 49.9). There was no significant relationship between
      the TBI-Index and distance of the bleed from recording sites (F = 0.044, p =
      0.833), or volume of blood measured F = 0.179, p = 0.674). Results of this study
      are a validation and extension of previously published retrospective findings in
      an independent population, and provide evidence that a TBI-Index for structural
      brain injury is a highly sensitive measure for the detection of potentially life
      threatening traumatic intracranial hematomas, and could contribute to the rapid,
      quantitative evaluation and treatment of such patients.

PMID- 25054840
TI  - Optimum feeding and growth in preterm neonates.
AB  - Approximately 10% of all babies worldwide are born preterm, and preterm birth is
      the leading cause of perinatal mortality in developed countries. Although preterm
      birth is associated with adverse short- and long-term health outcomes, it is not
      yet clear whether this relationship is causal. Rather, there is evidence that
      reduced foetal growth, preterm birth and the long-term health effects of both of
      these may all arise from a suboptimal intrauterine environment. Further, most
      infants born preterm also experience suboptimal postnatal growth, with potential
      adverse effects on long-term health and development. A number of interventions
      are used widely in the neonatal period to optimise postnatal growth and
      development. These commonly include supplementation with macronutrients and/or
      micronutrients, all of which have potential short-term risks and benefits for the
      preterm infant, whereas the long-term health consequences are largely unknown.
      Importantly, more rapid postnatal growth trajectory (and the interventions
      required to achieve this) may result in improved neurological outcomes at the
      expense of increased cardiovascular risk in later life. 

PMID- 25054839
TI  - Asymmetric synthesis of spiro[isoxazolin-3,3'-oxindoles] via the catalytic 1,3
      dipolar cycloaddition reaction of nitrile oxides.
AB  - A highly enantioselective 1,3-dipolar cycloaddition of nitrile oxides with 3
      arylidene-oxindoles was realized by a chiral N,N'-dioxide-nickel(II) complex
      catalyst under mild reaction conditions. A series of spiro-isoxazoline-oxindole
      derivatives were obtained in moderate yields (up to 65%) with good
      regioselectivities (up to 99:1), excellent enantioselectivities (up to 99% ee),
      and exclusive diastereoselectivity as well. 

PMID- 25054841
TI  - Disproportionate early fetal growth predicts postnatal thymic size in humans.
AB  - Prenatal events can affect neonatal thymus size and adult immune function. The
      causal insults are unknown, although fetal nutrient restriction is suspected. We
      used ultrasound at three time points during pregnancy (14, 19 and 30 weeks) to
      measure the growth of six fetal dimensions in rural Bangladeshi women
      participating in the Maternal and Infant Nutrition Interventions, Matlab study.
      Postnatal ultrasound was used to calculate thymic index (TI) at birth, 2, 6 and
      12 m. Of the 3267 women recruited, 2861 participated by providing data at least
      at one fetal biometry and one TI time point. Patterns of fetal growth were
      summarized using principal components calculated from fetal dimension z-scores.
      Random effects regression, controlling for infant size and season of measurement
      were used to relate these patterns to TI. We found that smaller leg length
      relative to head circumference, characteristic of head-sparing growth
      restriction, was predictive of lower TI. This association was significant at all
      time points but strongest in earlier pregnancy. Each standard deviation increase
      in leg-head proportion was associated with an increase in TI of ~5%. We conclude
      that growth patterns typical of poor fetal nutrition are associated with poor
      thymic development. The greater strength of this association in the first
      trimester is consistent with a period of vulnerability during the early ontogeny
      of the thymus and suggests that preventative intervention would need to be given
      in early pregnancy. 

PMID- 25054842
TI  - Association of perinatal factors and school performance in primary school Chilean
      children.
AB  - The associations between school performance and cognitive abilities with birth
      characteristics have mostly been studied without taking into consideration the
      effects of gestational age (GA). Our aim was to study the association between
      prenatal growth and cognitive function in term-born Chilean school children. A
      cohort of over 200,000 term-born fourth graders who took the regular national
      test for school performance was studied. Outcome parameters were language and
      mathematics test scores in relation to prenatal growth. A total of 256,040
      subjects took the test and 220,940 were included in the final study sample.
      Prenatal growth was modestly, but significantly, associated with school
      performance. Adjusted beta coefficients for 1 cm increase in birth length were
      1.28 and 0.77 for mathematics and language, respectively; the corresponding
      values for 100 g increase in birth weight were 0.59 and 0.34, respectively.
      Increased GA was associated with lower test scores. Adjusted beta coefficients
      for the birth measurements generally had a lower strength of association than
      those of socio-economic factors. However, the confounders most strongly
      associated with educational achievements were socio-economic factors, known to be
      associated with birth size. Lower socio-economic status is known to negatively
      influence both prenatal growth and cognitive function, supporting the overall
      importance of prenatal growth in relation to cognitive outcomes. 

PMID- 25054843
TI  - Mechanism of programmed obesity: altered central insulin sensitivity in growth
      restricted juvenile female rats.
AB  - Intrauterine growth-restricted (IUGR) offspring are at increased risk of adult
      obesity, as a result of changes in energy balance mechanisms. We hypothesized
      that impairment of hypothalamic insulin signaling contributes to hyperphagia in
      IUGR offspring. Study pregnant dams were 50% food restricted from days 10 to 21
      to create IUGR newborns. At 5 weeks of age, food intake was measured following
      intracerebroventricular (icv) injection of vehicle or insulin (10 mU) in control
      and IUGR pups. At 6 weeks of age, with pups in fed or fasted (48 h) states, pups
      received icv vehicle or insulin after which they were decapitated, and
      hypothalamic arcuate (ARC) nucleus dissected for RNA and protein expression. IUGR
      rats consumed more food than controls under basal conditions, consistent with
      upregulated ARC phospho AMP-activated protein kinase (pAMPK) and neuropeptide Y
      (NPY). Insulin acutely reduced food intake in both control and IUGR rats.
      Consistent with anorexigenic stimulation, central insulin decreased AMP-activated
      protein kinase and NPY mRNA expression and increased proopiomelanocortin mRNA
      expression and pAkt, with significantly reduced responses in IUGR as compared
      with controls. Despite feeding, IUGR offspring exhibit a persistent state of
      orexigenic stimulation in the ARC nucleus and relative resistance to the
      anorexigenic effects of icv insulin. These results suggest that impaired insulin
      signaling contributes to hyperphagia and obesity in IUGR offspring. 

PMID- 25054844
TI  - Reduced apoptosis in term placentas from gestational diabetic pregnancies.
AB  - Gestational diabetic mellitus (GDM) pregnancies have an increased risk of
      macrosomic infants and large placental mass, though the mechanisms explaining
      each of these is uncertain. We sought to evaluate the contribution of apoptosis
      to placental size and the expression of glucose transporters (SLC2A) in GDM
      pregnancies. Maternal age and pre-pregnancy body weight were documented. Newborn
      weights were recorded after delivery. Placentas 37-40-week gestation from control
      patients (no pregnancy complication) (n = 5), or with GDM (n = 5) were weighed
      immediately after delivery. Villous samples (4 mm diameter) were collected and
      divided into specimens; one was fixed in 4% paraformaldehyde for immunostaining
      using terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling
      (TUNEL) and activated caspase-3. The other specimen was snap frozen in liquid
      nitrogen and stored at -80 degrees C for active caspase-3, poly(ADP-ribose)
      polymerase (PARP), SLC2A1 and SLC2A3 gene expression analysis. Our results showed
      that maternal age and pre-pregnancy body weight were significantly higher in the
      GDM group when compared with those from the controls (P < 0.05). The mean
      neonatal birth weight and placenta weight were significantly higher in the GDM
      group compared with that from the controls (P < 0.05). The apoptotic index of
      placentas (0.05 +/- 0.01 v. 0.17 +/- 0.04, P < 0.04), active caspase-3
      polypeptide fragments and PARP protein were significantly decreased in GDM
      placentas as compared with controls. Further, the level of placental SLC2A1
      protein expression was ~3-fold higher in GDM placentas. Our results suggest that
      reduced apoptosis in GDM placentas may contribute to increased placental tissue,
      which together with enhanced SLC2A1 expression, could play a role in fetal
      macrosomia. 

PMID- 25054845
TI  - Effects of protocol step length on biomechanical measures in swimming.
AB  - BACKGROUND: The assessment of energetic and mechanical parameters in swimming
      often requires the use of an intermittent incremental protocol, whose step
      lengths are corner stones for the efficiency of the evaluation procedures.
      PURPOSE: To analyze changes in swimming kinematics and interlimb coordination
      behavior in 3 variants, with different step lengths, of an intermittent
      incremental protocol. METHODS: Twenty-two male swimmers performed n*di variants
      of an intermittent and incremental protocol (n<=7; d1=200 m, d2=300 m, and d3=400
      m). Swimmers were videotaped in the sagittal plane for 2-dimensional kinematical
      analysis using a dual-media setup. Video images were digitized with a motion
      capture system. Parameters that were assessed included the stroke kinematics, the
      segmental and anatomical landmark kinematics, and interlimb coordination.
      Movement efficiency was also estimated. RESULTS: There were no significant
      variations in any of the selected variables according to the step lengths. A high
      to very high relationship was observed between step lengths. The bias was much
      reduced and the 95%CI fairly tight. CONCLUSIONS: Since there were no meaningful
      differences between the 3 protocol variants, the 1 with shortest step length (ie,
      200 m) should be adopted for logistical reasons.

PMID- 25054847
TI  - Plasma Abeta but not tau is related to brain PiB retention in early Alzheimer's
      disease.
AB  - Recent advances in biomarkers provide the possibility of early or preclinical
      diagnosis of Alzheimer's pathology. Currently, decreased levels of Abeta-42 and
      increased levels of tau proteins in cerebral spinal fluid are considered reliable
      biomarkers of Alzheimer's disease (AD); however, little evidence exists for the
      use of amyloid and tau protein levels in the plasma as useful biomarkers. We
      investigated the potential use of plasma biomarkers to diagnose AD and explored
      their relationships with brain Abeta deposition in amyloid imaging. We used an
      immunomagnetic reduction assay to measure the plasma levels of Abeta40, Abeta42,
      and tau proteins in 20 older control participants and 25 participants who had
      either mild cognitive impairment due to AD or early AD dementia. All participants
      received (11)C-labeled Pittsburgh compound B PET scans. The sensitivity of the
      plasma tau level at the cutoff value of 28.27 pg/mL was 92%, and the specificity
      was 100%; the sensitivity of the Abeta42/40 ratio at the cutoff value of 0.3693
      was 84%, and the specificity was 100%. Regression analyses of the effects of
      plasma protein levels on brain amyloid retention, as determined by standard
      uptake value ratios in either side of the frontal, parietal, and temporal lobes
      and the precuneus, are predicted only by ratios of plasma Abeta42/40 (R(2) 0.326
      0.449, all p < 0.001) but not by plasma tau levels. Plasma Abeta in terms of
      Abeta42/40 might provide an indirect estimation of Abeta deposition in the brain.

PMID- 25054848
TI  - Cu(I)-catalyzed macrocyclic Sonogashira-type cross-coupling.
AB  - A macrocyclic Cu-catalyzed Sonogashira-type cross-coupling reaction has been
      developed that employs an operationally simple CuCl/phen/Cs2CO3 catalyst system.
      Macrocyclizations can be performed at relatively high concentrations without the
      need for slow addition techniques and form macrocycles with various ring sizes
      and functional groups. The optimized protocol was employed in the synthesis of
      (S)-zearalane, demonstrating applicability toward the synthesis of a macrocycle
      with known biological activity. 

PMID- 25054849
TI  - Daily functioning profile of children with attention deficit hyperactive
      disorder: A pilot study using an ecological assessment.
AB  - Children with attention-deficit hyperactivity disorder (ADHD) often present with
      activities of daily living (ADL) performance deficits. This study aimed to
      compare the performance characteristics of children with ADHD to those of
      controls based on the Do-Eat assessment tool, and to establish the tool's
      validity. Participants were 23 children with ADHD and 24 matched controls, aged 6
      9 years. In addition to the Do-Eat, the Children Activity Scale-Parent (ChAS-P)
      and the Behavioral Rating Inventory of Executive Function (BRIEF) were used to
      measure sensorimotor abilities and executive function (EF). Significant
      differences were found in the Do-Eat scores between children with ADHD and
      controls. Significant moderate correlations were found between the Do-Eat
      sensorimotor scores, the ChAS-P and the BRIEF scores in the ADHD group.
      Significant correlations were found between performance on the Do-Eat and the
      ChAS-P questionnaire scores, verifying the tool's ecological validity. A single
      discriminant function described primarily by four Do-Eat variables, correctly
      classified 95.5% of the study participants into their respective study groups,
      establishing the tool's predictive validity within this population. These
      preliminary findings indicate that the Do-Eat may serve as a reliable and valid
      tool that provides insight into the daily functioning characteristics of children
      with ADHD. However, further research on larger samples is indicated. 

PMID- 25054850
TI  - Assessing science.

PMID- 25054851
TI  - Science budget: funding by numbers.

PMID- 25054852
TI  - Research metrics: calling science to account.

PMID- 25054853
TI  - Research assessment: the limits of excellence.

PMID- 25054854
TI  - Perspective: on the verge of a new ERA.

PMID- 25054855
TI  - Research impact: income for outcome.

PMID- 25054856
TI  - Perspective: powering up citations.

PMID- 25054857
TI  - Perspective: if not funding then teaching.

PMID- 25054858
TI  - Q&A Jane Harding: individual approach.

PMID- 25054859
TI  - Quantification of iopamidol multi-site chemical exchange properties for
      ratiometric chemical exchange saturation transfer (CEST) imaging of pH.
AB  - pH-sensitive chemical exchange saturation transfer (CEST) MRI holds great promise
      for in vivo applications. However, the CEST effect depends on not only exchange
      rate and hence pH, but also on the contrast agent concentration, which must be
      determined independently for pH quantification. Ratiometric CEST MRI normalizes
      the concentration effect by comparing CEST measurements of multiple labile
      protons to simplify pH determination. Iopamidol, a commonly used x-ray contrast
      agent, has been explored as a ratiometric CEST agent for imaging pH. However,
      iopamidol CEST properties have not been solved, determination of which is
      important for optimization and quantification of iopamidol pH imaging. Our study
      numerically solved iopamidol multi-site pH-dependent chemical exchange
      properties. We found that iopamidol CEST MRI is suitable for measuring pH between
      6 and 7.5 despite that T1 and T2 measurements varied substantially with pH and
      concentration. The pH MRI precision decreased with pH and concentration. The
      standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and
      20 mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH
      above 7. Moreover, we determined base-catalyzed chemical exchange for 2
      hydrooxypropanamido (ksw = 1.2*10(pH-4.1)) and amide (ksw = 1.2*10(pH-4.6))
      protons that are statistically different from each other (P < 0.01, ANCOVA),
      understanding of which should help guide in vivo translation of iopamidol pH
      imaging. 

PMID- 25054860
TI  - Sex differences in first-admission psychiatric inpatients with and without a
      comorbid substance use disorder.
AB  - OBJECTIVES: We assessed sex differences in a sample of first-admission
      psychiatric inpatients with and without comorbid substance use disorder (SUD) to
      identify possible risk factors and targets for sex-tailored treatment
      interventions. METHODS: A retrospective study of first admissions to the
      University Psychiatry Ward, "Maggiore della Carita" Hospital, Novara, Italy,
      between 2003 and 2012 was accomplished. The clinical charts of patients with (N =
      362) and without comorbid SUD (N = 1111) were reviewed. RESULTS: Differences in
      employment, educational, and marital statuses were found between male and female
      psychiatric patients with and without comorbid SUD. Having a degree was a
      protective factor for males, whereas it was a risk factor for females. Being
      divorced and having family problems were both risk factors for comorbidity in
      females. Regarding the diagnosis, results overlapped in males and females, and
      both affective and other disorders were risk factors for a comorbid SUD.
      CONCLUSIONS: A significant difference between male and female psychiatric
      patients with a comorbid SUD was the males' overall poorer psychosocial
      functioning. Marital status and family problems were risk factors for comorbid
      SUD in females. Both males and females showed various pathways of access to and
      choices of substances and, eventually, experienced different impacts on their
      lives. Hospitalization might help to set up a targeted intervention for patients
      with comorbidity, while accounting for sex differences. With respect to males, a
      treatment approach focused on the substance alone might help improve their
      functioning; females might have a greater benefit from a treatment approach
      focused on distress, family problems, and relational issues.

PMID- 25054861
TI  - Genetic diversity of human enterovirus 68 strains isolated in Kenya using the
      hypervariable 3'-end of VP1 gene.
AB  - Reports of increasing worldwide circulation of human enterovirus-68 (EV68) are
      well documented. Despite health concerns posed by resurgence of these viruses,
      little is known about EV68 strains circulating in Kenya. In this study, we
      characterized 13 EV68 strains isolated in Kenya between 2008 and 2011 based on
      the Hypervariable 3'-end of the VP1 gene. Viral RNA was extracted from the
      isolates and partial VP1 gene amplified by RT-PCR, followed by nucleotide
      sequencing. Alignment of deduced amino acid sequences revealed substitutions in
      Kenyan EV68 isolates absent in the prototype reference strain (Fermon). The
      majority of these changes were present in the BC and DE-loop regions, which are
      associated with viral antigenicity and virulence. The Kenyan strains exhibited
      high sequence homology with respect to those from other countries. Natural
      selection analysis based on the VP1 region showed that the Kenyan EV68 isolates
      were under purifying selection. Phylogenetic analysis revealed that majority
      (84.6%) of the Kenyan strains belonged to clade A, while a minority belonged to
      clades B and C. Overall, our results illustrate that although EV68 strains
      isolated in Kenya were genetically and antigenically divergent from the prototype
      strain (Fermon), they were closely related to those circulating in other
      countries, suggesting worldwide transmissibility. Further, the presence of shared
      mutations by Kenyan EV68 strains and those isolated in other countries, indicates
      evolution in the VP1 region may be contributing to increased worldwide detection
      of the viruses. This is the first study to document circulation of EV68 in Kenya.

PMID- 25054862
TI  - The potential of mycelium and culture broth of Lignosus rhinocerotis as
      substitutes for the naturally occurring sclerotium with regard to antioxidant
      capacity, cytotoxic effect, and low-molecular-weight chemical constituents.
AB  - Previous studies on the nutritional and nutraceutical properties of Lignosus
      rhinocerotis focused mainly on the sclerotium; however, the supply of wild
      sclerotium is limited. In this investigation, the antioxidant capacity and
      cytotoxic effect of L. rhinocerotis cultured under different conditions of liquid
      fermentation (shaken and static) were compared to the sclerotium produced by
      solid-substrate fermentation. Aqueous methanol extracts of the mycelium (LR-MH,
      LR-MT) and culture broth (LR-BH, LR-BT) demonstrated either higher or comparable
      antioxidant capacities to the sclerotium extract (LR-SC) based on their radical
      scavenging abilities, reducing properties, metal chelating activities, and
      inhibitory effects on lipid peroxidation. All extracts exerted low cytotoxicity
      (IC50>200 ug/ml, 72 h) against selected mammalian cell lines. Several low
      molecular-weight compounds, including sugars, fatty acids, methyl esters,
      sterols, amides, amino acids, phenolics, and triterpenoids, were identified using
      GC-MS and UHPLC-ESI-MS/MS. The presence of proteins (<40 kDa) in the extracts was
      confirmed by SDS-PAGE and SELDI-TOF-MS. Principal component analysis revealed
      that the chemical profiles of the mycelial extracts under shaken and static
      conditions were distinct from those of the sclerotium. Results from bioactivity
      evaluation and chemical profiling showed that L. rhinocerotis from liquid
      fermentation merits consideration as an alternative source of functional
      ingredients and potential substitute for the sclerotium. 

PMID- 25054863
TI  - Mixed fortunes: ancient expansion and recent decline in population size of a
      subtropical montane primate, the Arunachal macaque Macaca munzala.
AB  - Quaternary glacial oscillations are known to have caused population size
      fluctuations in many temperate species. Species from subtropical and tropical
      regions are, however, considerably less studied, despite representing most of the
      biodiversity hotspots in the world including many highly threatened by
      anthropogenic activities such as hunting. These regions, consequently, pose a
      significant knowledge gap in terms of how their fauna have typically responded to
      past climatic changes. We studied an endangered primate, the Arunachal macaque
      Macaca munzala, from the subtropical southern edge of the Tibetan plateau, a part
      of the Eastern Himalaya biodiversity hotspot, also known to be highly threatened
      due to rampant hunting. We employed a 534 bp-long mitochondrial DNA sequence and
      22 autosomal microsatellite loci to investigate the factors that have potentially
      shaped the demographic history of the species. Analysing the genetic data with
      traditional statistical methods and advance Bayesian inferential approaches, we
      demonstrate a limited effect of past glacial fluctuations on the demographic
      history of the species before the last glacial maximum, approximately 20,000
      years ago. This was, however, immediately followed by a significant population
      expansion possibly due to warmer climatic conditions, approximately 15,000 years
      ago. These changes may thus represent an apparent balance between that displayed
      by the relatively climatically stable tropics and those of the more severe,
      temperate environments of the past. This study also draws attention to the
      possibility that a cold-tolerant species like the Arunachal macaque, which could
      withstand historical climate fluctuations and grow once the climate became
      conducive, may actually be extremely vulnerable to anthropogenic exploitation, as
      is perhaps indicated by its Holocene ca. 30-fold population decline,
      approximately 3,500 years ago. Our study thus provides a quantitative appraisal
      of these demographically important events, emphasising the ability to potentially
      infer the occurrence of two separate historical events from contemporary genetic
      data. 

PMID- 25054864
TI  - Strategic focus on 3R principles reveals major reductions in the use of animals
      in pharmaceutical toxicity testing.
AB  - The principles of the 3Rs, Replacement, Reduction and Refinement, are being
      increasingly incorporated into legislations, guidelines and practice of animal
      experiments in order to safeguard animal welfare. In the present study we have
      studied the systematic application of 3R principles to toxicological research in
      the pharmaceutical industry, with particular focus on achieving reductions in
      animal numbers used in regulatory and investigatory in vivo studies. The work
      also details major factors influencing these reductions including the conception
      of ideas, cross-departmental working and acceptance into the work process. Data
      from 36 reduction projects were collected retrospectively from work between 2006
      and 2010. Substantial reduction in animal use was achieved by different
      strategies, including improved study design, method development and project
      coordination. Major animal savings were shown in both regulatory and
      investigative safety studies. If a similar (i.e. 53%) reduction had been achieved
      simultaneously within the twelve largest pharmaceutical companies, the equivalent
      reduction world-wide would be about 150,000 rats annually. The results point at
      the importance of a strong 3R culture, with scientific engagement, collaboration
      and a responsive management being vital components. A strong commitment in
      leadership for the 3R is recommended to be translated into cross-department and
      inter-profession involvement in projects for innovation, validation and
      implementation. Synergies between all the three Rs are observed and conclude that
      in silico-, in vitro- and in vivo-methods all hold the potential for applying the
      reduction R and should be consequently coordinated at a strategic level. 

PMID- 25054865
TI  - Real-time visualization of diffusion-controlled nanowire growth in solution.
AB  - This Letter shows that copper nanowires grow through the diffusion-controlled
      reduction of dihydroxycopper(I), Cu(OH)2(-). A combination of potentiostatic
      coulometry, UV-visible spectroscopy, and thermodynamic calculations was used to
      determine the species adding to growing Cu nanowires is Cu(OH)2(-). Cyclic
      voltammetry was then used to measure the diffusion coefficient of Cu(OH)2(-) in
      the reaction solution. Given the diameter of a Cu nanowire and the diffusion
      coefficient of Cu(OH)2(-), we calculated the dependence of the diffusion-limited
      growth rate on the concentration of copper ions to be 26 nm s(-1) mM(-1).
      Independent measurements of the nanowire growth rate with dark-field optical
      microscopy yielded 24 nm s(-1) mM(-1) for the growth rate dependence on the
      concentration of copper. Dependence of the nanowire growth rate on temperature
      yielded a low activation energy of 11.5 kJ mol(-1), consistent with diffusion
      limited growth. 

PMID- 25054866
TI  - Jet-cooled laser-induced fluorescence spectroscopy of isopropoxy radical:
      vibronic analysis of B-X and B-A band systems.
AB  - Recently we published [ Liu et al. J. Chem. Phys. 2013 , 139 , 154312 ] an
      analysis of the rotational structure of the B-X origin band spectrum of
      isopropoxy, which confirmed that the double methyl substitution of methoxy to
      yield the isopropoxy radical only slightly lifted the degeneracy of the former's
      X(2)E state. Additionally the spectral results provided considerable insight into
      the relativistic and nonrelativistic contributions to the experimental splitting
      between the components of the (2)E state. However, left unexplained was how the
      Jahn-Teller (JT) vibronic coupling terms within methoxy's (2)E state manifest
      themselves as pseudo-Jahn-Teller (pJT) vibronic coupling between the A(2)A" and
      X(2)A' levels of isopropoxy. To cast additional light on this subject we have
      obtained new isopropoxy spectra and assigned a number of weak, "forbidden"
      vibronic transitions in the B-X spectrum using new electronic structure
      calculations and rotational contour analyses. The mechanisms that provide the
      nonzero probability for these transitions shed considerable information on pJT,
      spin-orbit, and Coriolis coupling between the A and X states. We also report a
      novel mechanism caused by pJT coupling that yields excitation probability to the
      B state dependent upon the permanent dipole moments in the B and A or X states.
      By combining a new B-A and the earlier B-X rotational analyses we determine a
      much improved value for the experimental A-X separation. 

PMID- 25054867
TI  - Ceragenin mediated selectivity of antimicrobial silver nanoparticles.
AB  - The understanding that common broad-spectrum antimicrobials disrupt natural
      microbial flora important in acquiring nutrients and preventing infection has
      resulted in a paradigm shift favoring more selective antimicrobials. This work
      explores silver nanoparticles conjugated with ceragenin, or cationic
      antimicrobials (CSA-SNPs), as a potential Gram-positive selective antimicrobial.
      Herein, CSA-SNPs are characterized using transmission electron microscopy (TEM),
      dynamic light scattering (DLS), zeta potential, and high-performance liquid
      chromatography-electrospray time-of-flight mass spectrometry (HPLC-ESI-TOF-MS).
      The antimicrobial properties are determined through minimum inhibitory
      concentration/minimum bactericidal concentration (MIC/MBC) and time-kill studies.
      Spatial selectivity of the conjugate nanoparticle was evaluated using confocal
      imaging, MATLAB statistical analysis, and video monitored interactions between
      bacteria and CSA-SNPs via laser trapping techniques. Cytotoxicity was also
      determined by live/dead staining and flow cytometry. Average particle size, as
      determined through TEM analysis, and hydrodynamic diameter, as determined via
      DLS, are 63.5 +/- 38.8 and 102.23 +/- 2.3 nm, respectively. The zeta potential of
      the SNP before and after CSA attachment is -18.23 and -8.34 mV, respectively.
      MIC/MBC data suggest that CSA-SNPs are 8 times more effective against
      Staphylococcus aureus than SNPs alone. Furthermore, MATLAB analysis of confocal
      imaging found that 70% of CSA-SNPs are within 2 MUm of S. aureus, whereas this
      percentage falls to below 40% with respect to Escherichia coli. These results are
      bolstered further by laser trapping experiments demonstrating selective adherence
      of CSA-SNPs conjugates with bacterial strains. Cytotoxicity studies of CSA-SNPs
      against 3T3 fibroblasts indicate 50% cell viability at 50 ppm. 

PMID- 25054868
TI  - Self-confidence for emergency intervention: adaptation and cultural validation of
      the Self-confidence Scale in nursing students.
AB  - OBJECTIVE: develop the cultural adaptation and validation of a Portuguese version
      of the Self-confidence Scale. METHOD: descriptive and exploratory methodological
      research for the adaptation and validation of a measuring instrument. The
      translation, synthesis, back-translation, revision, pretest and semantic
      evaluation phases were accomplished. The evaluation involving 178 students from a
      Teaching Diploma Program in Nursing. The ethical principles were complied with.
      RESULTS: the internal consistency analysis of the scale reveals good Alpha
      coefficients (0.92 for the global scale and superior to 0.83 for the different
      dimensions). The factor analysis presents a three-factor solution with rational
      meaning. CONCLUSION: The scale is easy to answer and understand. Based on the
      obtained results, it can be affirmed that the scale reveals good psychometric
      properties, with great potential to be used in future research.

PMID- 25054869
TI  - The principle of integrality of care in the political-pedagogical projects of
      nursing programs.
AB  - OBJECTIVE: to identify the political-pedagogical projects of the undergraduate
      nursing programs in Santa Catarina, Brazil according to the guidelines of the
      Ministries of Health and Education, considering the education of professionals
      under the principle of integrality. METHOD: documentary study with a qualitative
      approach. Nine projects were analyzed. RESULTS: the colleges from the Southern
      region of Brazil are gradually incorporating the theoretical framework of the
      Brazilian health system and curricular guidelines, which includes the principle
      of integrality of care, into their political-pedagogical projects of
      undergraduate nursing programs. Some institutions strictly follow the curricular
      guidelines, while others make their own interpretation. CONCLUSION: most teaching
      institutions do not provide pedagogical support to students.

PMID- 25054870
TI  - Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic
      doses on the fertility of female Wistar rats.
AB  - PURPOSE: To evaluate the effects of exposure of enoxaparin and unfractionated
      heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of
      pregnant healthy Wistar rats. METHODS: Enoxaparin and UFH were administered in
      prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2
      mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of
      live and dead foetuses was quantified. The uterine horns were dissected and the
      presence of early and late reabsorptions (abortions) was determined. A p<0.05 was
      considered statistically significant. RESULTS: We did not observe statistically
      significant differences between groups when comparing the average weight of the
      foetuses and placentas, rate of female VS males, rates of pre-implantation loss
      (RPL), rates of efficiency implantation (REI), rates of post-implantation loss
      (RPIL) and rates of foetal viability (RFV). CONCLUSIONS: There was no significant
      effect on fertility with the use of anticoagulant drugs in pregnant healthy
      Wistar rats.

PMID- 25054871
TI  - Experimental model of Achilles tendon injury in rats.
AB  - PURPOSE: To describe an effective experimental model to study the Achilles tendon
      healing. METHODS: Forty male Rattus norvegicus albinus, Wistar lineage adult male
      weighing 250 to 300g were used for this experiment and thirty were surgically
      submitted to bilateral partial transverse section of the Achilles tendon. The
      right tendon was treated with radio waves (RF) whereas the left tendon served as
      control. On the third postoperative day, the rats were divided into four
      experimental groups consisting of ten rats each which were treated with monopolar
      RF adjusted to 650 kHz and 2w, for two minutes twice a week and a group of normal
      animals without any intervention, until they were sacrificed on the 7th, 14th and
      28th days, respectively. Tendons were weighed and collagen quantification was
      evaluated by hydroxyprolin content. RESULTS: Significant reduction in collagen
      content on day 7, 14 and 28 was related to control experiment to normal tendon (7
      days, p<0.01; 14 e 28 days, p<0.05). CONCLUSION: The experimental model has been
      effective and available to be used to study Achilles tendon healing.

PMID- 25054872
TI  - Potential chemoprotective effects of green propolis, L-lysine and celecoxib on
      bone marrow cells and peripheral blood lymphocytes of Wistar rats subjected to
      bladder chemical carcinogenesis.
AB  - PURPOSE: To evaluate the genotoxicity of propolis and L-lysine, as well as their
      effects on the possible cellular damage in erythroblasts (bone marrow) and
      leukocytes (peripheral blood) caused by the carcinogen BBN (n - butyl - n {4 -
      hydroxybutyl} nitrosamine) in rats subjected to bladder carcinogenesis and
      treated with green propolis and L-lysine. METHODS: One hundred and twenty five
      rats were distributed into the following groups: I, IIA, IIB, III, K, L M N, X,
      XI, XII and XIII. Groups I to X received BBN in drinking water for 14 weeks
      (wks). Group I was treated with intragastric (ig) propolis at 150 mg/kg body
      weight, for 44 wks, beginning 30 days before start of BBN. Groups IIA and III
      were treated with propolis (150 mg/kg), for 40 wks, subcutaneous (sc) and ig,
      respectively, beginning simultaneously with BBN. On the 32nd wk, the animals of
      groups L, M and N were treated ig with L-lysine (300 mg/kg), celecoxib (30 mg/kg)
      and propolis (300 mg/kg), respectively, up to the 40th wk. The groups that
      received only BBN (IIB and K) were treated with water, sc and orally,
      respectively, for 40 wks. Groups XI, XII and XIII received respectively propolis
      (150 mg/kg), L-lysine (150 mg/kg) and water ig for 40 wks. After 40 wks, the
      surviving animals were anesthetized and subjected to femoral bone marrow
      aspiration and blood collection from the aorta, for CA and MNT, respectively, for
      investigation of genotoxicity. RESULTS: Groups IIB and K, which received only BBN
      and water, showed the greatest DNA damage in peripheral leukocytes (CA) and
      largest number of micronuclei in bone marrow erythrocytes (MNT) in relation to
      all other groups that received BBN and lysine and/or propolis (p<0.001).
      CONCLUSIONS: Both propolis and L-lysine are effective in protecting against
      genotoxicity, as well not being genotoxic themselves toward the cells evaluated,
      at the doses and times administered and according to the two tests utilized.

PMID- 25054873
TI  - Applicability of crystalline cellulose membrane in the treatment of skin wounds
      induced in Wistar rats.
AB  - PURPOSE: To evaluate the healing of skin wounds induced experimentally in rats
      using a crystalline cellulose membrane (Veloderm(r)). METHODS: Thirty-two rats
      were divided into two groups: control group (CG) wounds treated with a solution
      of 0.9% sodium chloride and Veloderm(r) group (VG) wounds treated with a
      crystalline cellulose membrane. The rats were evaluated at different times over
      twenty-six days. RESULTS: Weight loss was observed in the animals from both
      groups in the early stages, with greater weight in the VG animals at the end.
      Times of predominant hypothermia, pink color of the wound in both groups over all
      time points, increased granulation tissue in the CG animals, the presence of
      slight oozing from the wound and feature in the VG animals, more serous exudation
      of the bloody feature, greater wound contraction and pain in the CG animals and
      an absence of pain and earlier complete wound healing in the VG rats were also
      observed. CONCLUSION: The crystalline cellulose membrane is effective in the
      treatment of wounds in rats, easy to use, protects and maintains the humidity of
      the wound, decreases pain, eases the visualization and control of the evolution
      of the lesion.

PMID- 25054874
TI  - Effects of maternal ischemic preconditioning in the colon of newborn rats
      submitted to hypoxia-reoxygenation insult.
AB  - PURPOSE: To evaluate the effects of maternal remote ischemic preconditioning
      (IPCr) in the colonic mucosa of newborn rats subjected to hypoxia and
      reoxygenation. METHODS: Newborn Wistar rats were divided into three groups.
      Control Group (CG), Hypoxia and Reoxygenation Group (HRG) and Remote Ischemic
      Preconditioning Group (IPCrG). Hypoxia and reoxygenation was performed 2x per
      day, with an interval of 6 hours, on the 1st, 2nd and 3rd days of life, with 10
      minutes of CO2 at 100%, followed by 10 minutes O2 at 100%(HRG/IPCrG). The
      maternal IPCr was performed 24 hours before delivery by applying a rubber band
      tourniquet to the left hind limb (IPCrG). Segments of the colon underwent
      histological (HE) and immunohistochemical analysis for caspase-3 and COX - 2.
      RESULTS: The histological findings showed no intestinal mucosal damage in the CG
      group and severe lesions in HRG that was attenuated in the IPCrG (p<0.05). The
      expression of the apoptotic cells was lower in the HRG group than in the CG and
      IPCrG. The COX-2 expression was intense in HRG and attenuated in the IPCrG
      (p<0.05). CONCLUSIONS: Maternal IPCr protected the colonic mucosa of newborn rats
      subjected to hypoxia and reoxygenation, reducing the morphological alterations
      and inflammatory response. It ameliorates the occurrence of apoptosis, keeping
      the physiological process of renewal and regeneration in the epithelial lining of
      the colonic mucosa.

PMID- 25054875
TI  - Heparin modulates the expression of genes encoding pro and anti-apoptotic
      proteins in endothelial cells exposed to intestinal ischemia and reperfusion in
      rats.
AB  - PURPOSE: To investigate if expression of genes encoding pro and anti-apoptotic
      proteins in the rat enteric endothelial cells stimulated by intestinal ischemia
      followed by reperfusion (IR) can be modified by treatment with heparin (HP).
      METHODS: Eighteen adult Wistar rats were divided in three groups: sham group
      submitted to laparotomy only (SG), ischemia followed by reperfusion group (IRG);
      ischemia followed by reperfusion plus pretreatment with HP 100 mg.kg-1 (IRG+HP).
      Ischemia was performed by clamping of the superior mesenteric artery. After 60
      min of ischemia, metal clamps were removed for reperfusion for 120 min. Gene
      expression of encoding pro (Casp1, Casp6, Casp3, Cflar, Fas and Pgl) and anti
      apoptotic (Bcl2, Bcl2l1 and Naip2) proteins in rat enteric endothelial cells was
      evaluated by PCR microarray method. RESULTS: Compared to rat endothelial cells of
      SG, the expression of pro-apoptotic genes was up-regulated in IRG while anti
      apoptotic genes were down-regulated. In contrast, the expression of anti
      apoptotic genes in IRG+HP was up-regulated while pro-apoptotic genes was down
      regulated compared to SG. CONCLUSION: The attenuation by heparin of intestinal
      ischemia-reperfusion previously demonstrated in rodents could be related with
      ability of this drug to stimulate and reduce gene expression of encoding anti and
      pro-apoptotic proteins, respectively.

PMID- 25054876
TI  - Protective effects of abdominal electroacupuncture on oxidative stress and
      inflammation due to testis torsion/detorsion in rats.
AB  - PURPOSE: To evaluate the effects of acupuncture (Ac) and electroacupuncture (EAc)
      on oxidative stress and inflammation in testis torsion/detorsion (T/D) model in
      rats. METHODS: Thirty male Wistar rats were randomized into five groups. G1 Group
      (Sham) served as control. The remaining groups were submitted to spermatic cord
      torsion (720 degrees ) for 3 hours, followed by detorsion and reperfusion for 4
      hours. Before detorsion G3, G4 and G5 rats were treated with Ac, EAc 2Hz and EAc
      10 Hz, respectively, applied to acupoint Gulai (S-29) bilaterally under
      anesthesia for 5 minutes. Next, the testes were detorsioned and reperfused for 4
      hours. Afterwards, blood samples and the right testis were collected for
      biochemical assays: reduced Glutathione (GSH), Malonaldehyde (MDA),
      Myeloperoxidase (MPO). RESULTS: EAc stimulation (2 and 10 Hz) promoted
      significant increase in concentrations of GSH in plasma and testis of G4-G5 rats,
      compared with G1. There was significant increase of tissue MDA in groups G4-G5
      and plasma MDA in all groups, compared with G1. There was a significant reduction
      in MPO activity in groups G4-G5 compared with G1. CONCLUSION: Electroacupuncture
      stimulation (2 and 10 Hz) attenuates oxidative stress and inflammatory response
      in rats subjected to testicular torsion/detorsion.

PMID- 25054877
TI  - Urethral dysfunction due to alloxan-induced diabetes. Urodynamic and
      morphological evaluation.
AB  - PURPOSE: To evaluate the effect of short and long term alloxan-induced diabetes
      on bladder and urethral function of female rats, and also describing its
      correlated morphological alterations. METHODS: Thirty five female rats were
      divided into three groups: G1 (n=9), control group; G2 (n=17), six weeks alloxan
      induced diabetic rats; G3 (n=9), 20 weeks alloxan-induced diabetic rats.
      Functional evaluation was performed by cystometry and simultaneous measurements
      of the urethral pressure during bladder filling and voiding. Morphological
      evaluation was also performed with measurement of bladder and urethral fibrosis
      and collagen content and thickness of lamina propria and smooth muscle layers.
      RESULTS: The peak bladder pressures and contraction amplitudes were decreased in
      100% and 47% of the G3 and G2 groups respectively, when compared to control.
      Bladder overactivity was observed in 53% of the G2 group. CONCLUSION: Alloxan
      induced diabetes urethropathty in female rat was associated to bladder
      morphological alterations as higher thicknesses of it lamina propria, detrusor
      and adventicea.

PMID- 25054878
TI  - Effects of continuous rate infusion of butorphanol in isoflurane-anesthetized
      calves.
AB  - PURPOSE: To assess the hemodynamic changes and bispectral index (BIS) following
      administration of a continuous rate infusion (CRI) of butorphanol in isoflurane
      anesthetized calves. METHODS: Eight calves weighing 110 +/- 12 kg were included
      in the study. Anesthesia was induced with 5% isoflurane in O2 delivered via face
      mask and maintained with end-tidal concentration of 1.4%. IPPV was set to a peak
      inspiratory airway pressure of 15 cmH2O and respiratory rate of six breaths
      minute-1. Forty minutes after the start of anesthetic maintenance, 0.1 mg kg
      1butorphanol was administered intravenously, followed by a CRI of 20 ug kg-1
      minute-1. Hemodynamic variables and BIS were recorded before butorphanol
      administration (T0), and at 10, 20, 40 and 80 minutes following the CRI.
      Anesthesia was discontinued after the last recording and the calves were allowed
      to recover. The time to sternal recumbency (SRE) and standing (ST) were
      evaluated. RESULTS: There were no significant differences between the moments in
      all hemodynamic variables and BIS. The time to SRE and ST was 9 +/- 5 and 14 +/-
      7 minutes, respectively. CONCLUSION: The continuous rate infusion did not produce
      clinically relevant changes in hemodynamic or bispectral index values compared to
      baseline in mechanically ventilated and unstimulated calves anesthetized at 1.4%
      isoflurane.

PMID- 25054879
TI  - Effects caused by the spinal administration of ketamine S (+) 5% with no
      preservatives, using a single puncture, and located on the spinal cord and
      meninges in rabbits.
AB  - PURPOSE: To evaluate the effect of ketamine S (+) 5% with no preservatives and
      administered as a subarachnoid single puncture on the spinal cord and meninges of
      rabbits. METHODS: Twenty young adult female rabbits, each weighing 3500-5000 g
      and having a spine length between 34 and 38 cm, were divided by lot into two
      groups (G): 0.9% saline in G1 and ketamine S (+) 5% in G2, by volume of 5 MUg per
      cm column (0.18 mL). After intravenous anaesthesia with ketamine and xylazine,
      the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a
      random solution was injected. The animals remained in captivity for 21 days under
      medical observation and were sacrificed by decapitation. The lumbosacral spinal
      cord portion was removed for immunohistochemistry to assess the glial fibrillary
      acidic protein (GFAP), and histology was assessed using hematoxylin and eosin
      (HE) stain. RESULTS: No histological lesions were found in the nervous tissue
      (roots and cord) or meninges in either group. CONCLUSION: The ketamine S (+) 5%
      unpreserved triggered no neurological or histological lesions in the spinal cord
      or meninges of rabbits.

PMID- 25054880
TI  - String theory--the physics of string-bending and other electric guitar
      techniques.
AB  - Electric guitar playing is ubiquitous in practically all modern music genres. In
      the hands of an experienced player, electric guitars can sound as expressive and
      distinct as a human voice. Unlike other more quantised instruments where pitch is
      a discrete function, guitarists can incorporate micro-tonality and, as a result,
      vibrato and sting-bending are idiosyncratic hallmarks of a player. Similarly, a
      wide variety of techniques unique to the electric guitar have emerged. While the
      mechano-acoustics of stringed instruments and vibrating strings are well studied,
      there has been comparatively little work dedicated to the underlying physics of
      unique electric guitar techniques and strings, nor the mechanical factors
      influencing vibrato, string-bending, fretting force and whammy-bar dynamics. In
      this work, models for these processes are derived and the implications for guitar
      and string design discussed. The string-bending model is experimentally validated
      using a variety of strings and vibrato dynamics are simulated. The implications
      of these findings on the configuration and design of guitars is also discussed. 

PMID- 25054881
TI  - Multiple E-boxes in the distal promoter of the rat pyruvate carboxylase gene
      function as a glucose-responsive element.
AB  - Pyruvate carboxylase (PC) is an anaplerotic enzyme that regulates glucose-induced
      insulin secretion in pancreatic islets. Dysregulation of its expression is
      associated with type 2 diabetes. Herein we describe the molecular mechanism
      underlying the glucose-mediated transcriptional regulation of the PC gene.
      Incubation of the rat insulin cell line INS-1 832/13 with glucose resulted in a 2
      fold increase in PC mRNA expression. Transient transfections of the rat PC
      promoter-luciferase reporter construct in the above cell line combined with
      mutational analysis indicated that the rat PC gene promoter contains the glucose
      responsive element (GRE), comprising three canonical E-boxes (E1, E3 and E4) and
      one E-box-like element (E2) clustering between nucleotides -546 and -399,
      upstream of the transcription start site. Mutation of any of these E-boxes
      resulted in a marked reduction of glucose-mediated transcriptional induction of
      the reporter gene. Electrophoretic mobility shift assays revealed that the
      upstream stimulatory factors 1 and 2 (USF1 and USF2) bind to E1, the Specificity
      Protein-1 (Sp1) binds to E2, USF2 and the carbohydrate responsive element binding
      protein (ChREBP) binds to E4, while unknown factors binds to E3. High glucose
      promotes the recruitment of Sp1 to E2 and, USF2 and ChREBP to E4. Silencing the
      expression of Sp1, USF2 and ChREBP by their respective siRNAs in INS-1 832/13
      cells blunted glucose-induced expression of endogenous PC. We conclude that the
      glucose-mediated transcriptional activation of the rat PC gene is regulated by at
      least these three transcription factors. 

PMID- 25054882
TI  - Dendritic morphology of caudal periaqueductal gray projecting retinal ganglion
      cells in Mongolian gerbil (Meriones unguiculatus).
AB  - In this study we investigated the morphological features of the caudal
      periaqueductal gray (cPAG)-projecting retinal ganglion cells (RGCs) in Mongolian
      gerbils using retrograde labeling, in vitro intracellular injection, confocal
      microscopy and three-dimensional reconstruction approaches. cPAG-projecting RGCs
      exhibit small somata (10-17 um) and irregular dendritic fields (201-298 um).
      Sizes of somata and dendritic fields do not show obvious variation at different
      distance from the optic disk (eccentricity). Dendrites are moderately branched.
      Morphological analysis (n = 23) reveals that cPAG-projecting RGCs ramified in
      sublamina a and b in the inner plexiform layer. These cells exhibit different
      stratification patterns based on the thickness of dendritic bands in sublaminas a
      and b: majority of analyzed cells (16 out of 23) have two bands of arborizations
      share similar thickness. The rest of analyzed cells (7 out of 23) exhibit thinner
      band in sublamina a than in sublamina b. Together, the present study suggests
      that cPAG of Mongolian gerbil could receive direct retinal inputs from two types
      of bistratified RGCs. Furthermore, a small subset of melanopsin-expressing RGCs
      (total 41 in 6 animals) is shown to innervate the rostral PAG (rPAG). Functional
      characteristics of these non-visual center projecting RGCs remain to be
      determined.

PMID- 25054884
TI  - Resistance analyses of integrase strand transfer inhibitors within phase 3
      clinical trials of treatment-naive patients.
AB  - The integrase (IN) strand transfer inhibitors (INSTIs), raltegravir (RAL),
      elvitegravir (EVG) and dolutegravir (DTG), comprise the newest drug class
      approved for the treatment of HIV-1 infection, which joins the existing classes
      of reverse transcriptase, protease and binding/entry inhibitors. The efficacy of
      first-line regimens has attained remarkably high levels, reaching undetectable
      viral loads in 90% of patients by Week 48; however, there remain patients who
      require a change in regimen due to adverse events, virologic failure with
      emergent resistance or other issues of patient management. Large, randomized
      clinical trials conducted in antiretroviral treatment-naive individuals are
      required for drug approval in this population in the US, EU and other countries,
      with the primary endpoint for virologic success at Week 48. However, there are
      differences in the definition of virologic failure and the evaluation of drug
      resistance among the trials. This review focuses on the methodology and
      tabulation of resistance to INSTIs in phase 3 clinical trials of first-line
      regimens and discusses case studies of resistance. 

PMID- 25054883
TI  - Membranous replication factories induced by plus-strand RNA viruses.
AB  - In this review, we summarize the current knowledge about the membranous
      replication factories of members of plus-strand (+) RNA viruses. We discuss
      primarily the architecture of these complex membrane rearrangements, because this
      topic emerged in the last few years as electron tomography has become more widely
      available. A general denominator is that two "morphotypes" of membrane
      alterations can be found that are exemplified by flaviviruses and hepaciviruses:
      membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and
      double membrane vesicles, representing extrusions also originating from the ER,
      respectively. We hypothesize that either morphotype might reflect common pathways
      and principles that are used by these viruses to form their membranous
      replication compartments. 

PMID- 25054886
TI  - Diarrheal outbreak caused by atypical enteropathogenic Escherichia coli O157:H45
      in South Korea.
AB  - Background: In May 2013, an outbreak of gastroenteritis occurred in a high school
      in Incheon, South Korea. We investigated the outbreak in order to identify the
      pathogen and mode of transmission. MATERIALS AND METHODS: A case-control study
      was performed using standardized questionnaires with a case definition of illness
      with diarrhea. Stool samples, environmental samples, and samples from preserved
      food items were collected to test pathogens. Pulsed-field gel electrophoresis
      (PFGE) was performed on the outbreak-related Escherichia coli strains. RESULTS:
      Thirty-three people (attack rate: 2.5%) met the case definition, and the pattern
      of the epidemic curve suggested a point-source outbreak. The common symptoms of
      cases were diarrhea (100.0%), abdominal pain (75.8%), chills (45.5%), and nausea
      (39.4%). Cases were found to be 8.26 times more likely to have eaten spicy fish
      soup with cod (95% confidence interval: 1.05-65.01). Consumption of egg soup with
      spring onions or braised eggs with razor clam flesh was significantly associated
      with illness. Atypical enteropathogenic E. coli O157:H45 was isolated from
      samples of 9 cases (27.3%) and tuna bibimbap. PFGE patterns of all tested
      isolates of O157 serotype were indistinguishable. CONCLUSIONS: This outbreak was
      caused by atypical enteropathogenic E. coli O157:H45 and the food vehicle was
      suspected to be tuna bibimbap. The statistical analysis was not in concordance
      with the microbiologic tests, probably owing to low pathogenicity of atypical
      enteropathogenic E. coli O157. This is the first report of an outbreak caused by
      atypical enteropathogenic E. coli O157.

PMID- 25054885
TI  - Full-length genome analyses of two new simian immunodeficiency virus (SIV)
      strains from mustached monkeys (C. Cephus) in Gabon illustrate a complex
      evolutionary history among the SIVmus/mon/gsn lineage.
AB  - The Simian Immunodeficiency Virus (SIV) mus/mon/gsn lineage is a descendant of
      one of the precursor viruses to the HIV-1/SIVcpz/gor viral lineage. SIVmus and
      SIVgsn were sequenced from mustached and greater spot nosed monkeys in Cameroon
      and SIVmon from mona monkeys in Cameroon and Nigeria. In order to further
      document the genetic diversity of SIVmus, we analyzed two full-length genomes of
      new strains identified in Gabon. The whole genomes obtained showed the expected
      reading frames for gag, pol, vif, vpr, tat, rev, env, nef, and also for a vpu
      gene. Analyses showed that the Gabonese SIVmus strains were closely related and
      formed a monophyletic clade within the SIVmus/mon/gsn lineage. Nonetheless,
      within this lineage, the position of both new SIVmus differed according to the
      gene analyzed. In pol and nef gene, phylogenetic topologies suggested different
      evolutions for each of the two new SIVmus strains whereas in the other nucleic
      fragments studied, their positions fluctuated between SIVmon, SIVmus-1, and
      SIVgsn. In addition, in C1 domain of env, we identified an insertion of seven
      amino acids characteristic for the SIVmus/mon/gsn and HIV-1/SIVcpz/SIVgor
      lineages. Our results show a high genetic diversity of SIVmus in mustached
      monkeys and suggest cross-species transmission events and recombination within
      SIVmus/mon/gsn lineage. Additionally, in Central Africa, hunters continue to be
      exposed to these simian viruses, and this represents a potential threat to
      humans. 

PMID- 25054887
TI  - A unilateral orbital mass.

PMID- 25054889
TI  - Photochromism of the natural dye 7,4'-dihydroxy-5-methoxyflavylium
      (dracoflavylium) in the presence of (2-hydroxypropyl)-beta-cyclodextrin.
AB  - A photochromic system based on dracoflavylium, a natural pigment extracted from
      Dragon's blood, a resin appearing in the injury parts of the tree Dracaena draco,
      is studied in water. The photochromism arises from the irradiation of the trans
      chalcone, giving a mixture of flavylium cation/quinoidal base as a photoproduct
      via cis-chalcone and hemiketal. The performance of the photochromic system can be
      improved in the presence of (2-hydroxypropyl)-beta-cyclodextrin. A mathematical
      model to account for the details of the kinetics and thermodynamics of the system
      was deduced. The model is general for all the host-guest systems involving the
      flavylium network of chemical reactions with 1 : 1 stoichiometric association. 

PMID- 25054888
TI  - Facilitating behavioral learning and habit change in voice therapy--theoretic
      premises and practical strategies.
AB  - A typical goal of voice therapy is a behavioral change in the patient's everyday
      speech. The SLP's plan for voice therapy should therefore optimally include
      strategies for automatization. The aim of the present study was to identify and
      describe factors that promote behavioral learning and habit change in voice
      behavior and have the potential to affect patient compliance and thus therapy
      outcome. Research literature from the areas of motor and behavioral learning,
      habit formation, and habit change was consulted. Also, specific elements from
      personal experience of clinical voice therapy are described and discussed from a
      learning theory perspective. Nine factors that seem to be relevant to facilitate
      behavioral learning and habit change in voice therapy are presented, together
      with related practical strategies and theoretical underpinnings. These are: 1)
      Cue-altering; 2) Attention exercises; 3) Repetition; 4) Cognitive activation; 5)
      Negative practice; 6) Inhibition through interruption; 7) Decomposing complex
      behavior; 8) The 'each time-every time' principle; and 9) Successive
      implementation of automaticity. 

PMID- 25054890
TI  - The influence of ethnicity on the outcomes of violence in pregnancy.
AB  - AIM: To investigate the influence of ethnicity on immediate and long-term (five
      years post-partum) foetal, maternal and injury-related outcomes. METHODS: A
      retrospective, population-based study analysing maternal discharge records linked
      to birth/death certificates for women aged 25 years and under. Discharge records
      were grouped according to ethnicity (Maori and non-Maori) and as follows: (1) a
      pregnancy-related hospital admission, but no associated or subsequent assault
      recorded (pregnant only); (2) an assault-related hospital admission event after
      the pregnancy, but within five years of the index pregnancy (assault after
      pregnancy); and (3) an assault recorded within the same hospital admission event
      as the pregnancy (assault during pregnancy). Generalised linear models for the
      binomial family were conducted to explore increased risk ratios of pregnancy
      related and subsequent injury outcomes depending on ethnicity and group
      assignment. RESULTS: Compared with the pregnancy-only group, rate ratios (RRs)
      for maternal and foetal outcomes were higher in the assault after pregnancy group
      and the assault during pregnancy group. For injury outcomes in the five years
      after the injury event, RRs for the assault after pregnancy group exceeded both
      the pregnancy-only and the assault during pregnancy groups. RRs for non-Maori
      women assaulted after pregnancy were higher for injury hospitalisations, fracture
      and intracranial injury than those for Maori women. CONCLUSION: Given that Maori
      women experience a higher prevalence of severe intimate partner violence and more
      difficulties accessing health care, we suggest that the findings highlight
      potential problems for health care access for Maori women experiencing violence.

PMID- 25054891
TI  - Bevacizumab therapy for glioblastoma: a passionate discussion.

PMID- 25054892
TI  - How efficient are autophagy inhibitors as treatment for glioblastoma?

PMID- 25054893
TI  - Which therapeutic approach is feasible for elderly people with glioblastoma?

PMID- 25054896
TI  - Brain cancer translational research from an academic perspective.
AB  - Dr Gregory Riggins speaks to Simi Thankaraj, Assistant Commisioning Editor:
      Gregory J Riggins is the recipient of the Irving J Sherman MD Research
      Professorship in Neurosurgery and the Director of the Division of Neurosurgery
      Research. He received his MD and PhD degrees from Emory University (GA, USA)
      where he graduated from the Medical Scientist Training Program. After graduation,
      he then trained as a postdoctoral fellow with Bert Vogelstein and Ken Kinzler at
      the Johns Hopkins University (MD, USA) in the Department of Oncology. Now a
      Professor of Neurosurgery and Oncology, and Genetic Medicine at Johns Hopkins,
      the main goal of his research is to develop and evaluate new brain tumor
      therapies. A major component of this research is identifying new small molecules.

PMID- 25054897
TI  - Injecting hope into brain cancer treatment: is immunotherapy the way forward?
AB  - Pierre-Yves Dietrich is a Full Professor of Medicine at the University of Geneva
      (Geneva, Switzerland) and Director of the Centre of Oncology in the Geneva
      University Hospital (Geneva, Switzerland). Since the early 1990s, his clinical
      and research activities have focused on the interplay between cancer and the
      immune system. He founded the Laboratory of Tumor Immunology in the Geneva
      University Hospital in 1994 and investigated mouse brain tumor models as well as
      human gliomas to firmly establish the existence of antiglioma immunity, a concept
      that was being debated at the time owing to the special immune status of the
      brain. Dietrich then embarked upon translating these conceptual advances into
      glioma immunotherapy. This challenge involved identifying novel targets on the
      surface of glioma cells in vivo, an essential step in designing an efficacious
      vaccine. Thanks to a fruitful collaboration with Immatics (Tubingen, Germany), a
      spin-off from the University of Tubingen (Germany), this work led to the
      identification of ten novel glioma-associated antigens with high expression on
      tumor cells and faint or absent expression on normal tissues, an indispensable
      feature to avoid autoimmunity. This crucial advance allowed the initiation of
      clinical trials of peptide vaccination in patients with gliomas as well as the
      development of T-cell therapy.

PMID- 25054898
TI  - Medulloblastoma treatment in a child on dialysis.
AB  - Managing patients who suffer from both cancer and end-stage renal disease is
      challenging because there is a paucity of data, especially for children. There
      are no published reports of adjuvant chemotherapy for medulloblastoma being used
      in children on dialysis. In this article we describe the case of an Italian 5
      year-old boy on hemodialysis for chronic renal failure who presented with a
      desmoplastic medulloblastoma with extensive nodularity and nuclear beta-catenin
      expression. The patient was treated with craniospinal irradiation after complete
      surgical resection, followed by six cycles of cyclophosphamide and vincristine.
      Vincristine was administered at the usual dosage for children with normal kidney
      function, cyclophosphamide was delivered after dialysis and over the course of
      the following day, starting with 50% of the commonly used dosage. This is the
      first case report of chemotherapy given during hemodialysis in a child with
      medulloblastoma. This treatment proved easy to administer despite the child's
      kidney disease and it maintained disease remission with no additional toxicity.

PMID- 25054899
TI  - Symptom management and quality of life in glioma patients.
AB  - Symptoms of fatigue, cognitive deficits, depression and changes in personality
      and behavior are frequently reported in patients with glioma. These symptoms have
      a large impact on the everyday life of patients and their partners and can
      contribute to a decrease in quality of life. While guidelines are available for
      managing most of these symptoms, these guidelines are often not suitable for the
      brain tumor patient population, as this population has very specific problems and
      needs. Obtaining more evidence on the effectiveness of existing and new
      interventions targeting fatigue, cognitive deficits, depression, and changes in
      personality and behavior in this population is advised. Screening combined with
      adequate referral to supportive care professionals has the potential to decrease
      the disease burden of glioma patients and their partners.

PMID- 25054900
TI  - The fine structure of ependymomas.
AB  - Electron microscopy is a useful diagnostic technique in order to confirm or
      establish a definitive diagnosis in brain tumors that may have an atypical
      histological pattern, which requires a concrete diagnosis. In ependymomas,
      electron microscopy reveals morphological characters that have a pathognomonic
      diagnostic value, therefore allowing a definitive diagnosis. The main fine
      structural criteria of ependymomas consist of the numerous microvilli and cilia,
      which are incorporated in the cell body or extended freely in the intracellular
      space; the centriole or blepharoplast, which is located in the basis of the
      cilia; the large number of the fragmented microtubules in the perikaryon and the
      cellular processes (any small cellular projection into the neutrophil or
      intracellular space); the junctional apparatus between the cells, such as zonula
      adherens, zonula occludens and puncta adherentia; the basement membrane-like
      structure, seen in papillary ependymomas and ependymomas of the filum terminale;
      and the elongated cells in the loose intracellular space, commonly seen in
      myxopapillary ependymomas.

PMID- 25054901
TI  - Brain metastases in non-small-cell lung cancer: better outcomes through current
      therapies and utilization of molecularly targeted approaches.
AB  - Non-small-cell lung cancer (NSCLC) patients experience a high incidence of brain
      metastases, de novo and recurrent. We review the mechanisms of brain metastases
      and promising NSCLC molecular markers to delineate potential future therapeutic
      targets. Discussed are the current and previously utilized roles of surgery,
      radiation (both therapeutic and prophylactic), and systemic therapies in the
      treatment of NSCLC brain metastases. Future directions for treatment of NSCLC
      brain metastases will conclude our review.

PMID- 25054903
TI  - Maximal sprint speed in boys of increasing maturity.
AB  - The purpose of this study was to examine the natural development of the
      mechanical features of sprint performance in relation to maturation within a
      large cohort of boys. Three hundred and thirty-six boys (11-15 years) were
      analyzed for sprint performance and maturation. Maximal speed, stride length
      (SL), stride frequency (SF), flight time (FT) and contact time (CT) were assessed
      during a 30m sprint. Five maturation groups (G1-5) were established based on age
      from peak height velocity (PHV) where G1=>2.5years pre-PHV, G2 = 2.49-1.5years
      pre-PHV, G3 = 1.49-0.5years pre-PHV, G4 = 0.49years pre- to 0.5years post-PHV and
      G5 = 0.51-1.5years post-PHV. There was no difference in maximal speed between G1,
      G2 and G3 but those in G4 and G5 were significantly faster (p < .05) than G1-3.
      Significant increases (p < .05) in SL were observed between groups with advancing
      maturation, except G4 and G5 (p > .05). SF decreased while CT increased (both p <
      .05) between G1, G2 and G3, but no further significant changes (p > .05) were
      observed for either variable between G3, G4 and G5. While G1-3 increased their
      SL, concomitant decreases in SF and increases in CT prevented them from improving
      maximal speed. Maximal sprint speed appears to develop around and post-PHV as SF
      and CT begin to stabilize, with increases in maximal sprint speed in maturing
      boys being underpinned by increasing SL. 

PMID- 25054902
TI  - Modern cerebrospinal fluid analyses for the diagnosis of diffuse large B-cell
      lymphoma of the CNS.
AB  - CNS lymphomas represent rare and aggressive variants of extranodal non-Hodgkin's
      lymphomas, which may present with diverse neurological symptoms and are often
      diagnostically challenging. Primary CNS lymphomas develop within the CNS and
      characteristically involve the brain, leptomeninges, eyes and, in rare cases,
      spinal cord. Secondary CNS lymphomas are characterized by expansion of systemic
      lymphomas to the CNS. Multimodal investigation of cerebrospinal fluid (CSF)
      comprises an important component of the diagnostic work-up for patients with
      suspected CNS lymphomas. Cytopathological examination of the CSF is still
      regarded as the 'gold standard' for the diagnosis of leptomeningeal malignant
      disease. However, cytopathology has only a low sensitivity in detecting
      leptomeningeal lymphoma involvement. Modern technologies including proteochemical
      and immunophenotypic studies by flow cytometry, and molecular genetic analyses of
      CSF may increase sensitivity and specificity, therefore, facilitating the
      diagnosis of CNS lymphomas. This review gives an overview and discussion of the
      current aspects of CSF analyses in CNS lymphomas.

PMID- 25054905
TI  - Malignant transformation of a 5-mm gallbladder polyp over 2 years: a case report
      and review of current literature.
AB  - Gallbladder polyps (GBPs) are incidentally seen in 4% to 7% of adults on
      abdominal ultrasounds. Most GBPs are benign cholesterol polyps, adenomyomatosis,
      or inflammatory polyps. Currently, cholecystectomy is widely accepted as
      appropriate care for polyps 10 mm or larger as they present a higher risk for
      malignancy. However, the management of small polyps smaller than 10 mm has
      continued to be a dilemma to clinicians and radiologists. Many authors support a
      nonoperative approach with imaging follow-up for polyps smaller than 10 mm, as
      most have been shown to be benign. However, small polyps do have the potential to
      be neoplastic adenomas and become malignant. In this report, we will describe a
      case of a tiny GBP that subsequently developed into a 20-mm carcinoma over a
      period of 2 years. 

PMID- 25054904
TI  - Separating fusion from rivalry.
AB  - Visual fusion is the process in which differing but compatible binocular
      information is transformed into a unified percept. Even though this is at the
      basis of binocular vision, the underlying neural processes are, as yet, poorly
      understood. In our study we therefore aimed to investigate neural correlates of
      visual fusion. To this end, we presented binocularly compatible, fusible (BF),
      and incompatible, rivaling (BR) stimuli, as well as an intermediate stimulus type
      containing both binocularly fusible and monocular, incompatible elements (BFR).
      Comparing BFR stimuli with BF and BR stimuli, respectively, we were able to
      disentangle brain responses associated with either visual fusion or rivalry. By
      means of functional magnetic resonance imaging, we measured brain responses to
      these stimulus classes in the visual cortex, and investigated them in detail at
      various retinal eccentricities. Compared with BF stimuli, the response to BFR
      stimuli was elevated in visual cortical areas V1 and V2, but not in V3 and V4 -
      implying that the response to monocular stimulus features decreased from V1 to
      V4. Compared to BR stimuli, the response to BFR stimuli decreased with increasing
      eccentricity, specifically within V3 and V4. Taken together, it seems that
      although the processing of exclusively monocular information decreases from V1 to
      V4, the processing of binocularly fused information increases from earlier to
      later visual areas. Our findings suggest the presence of an inhibitory neural
      mechanism which, depending on the presence of fusion, acts differently on the
      processing of monocular information.

PMID- 25054906
TI  - Emphysematous cholecystitis.

PMID- 25054907
TI  - The coagulopathy of cancer.
AB  - PURPOSE OF REVIEW: To provide an updated overview of the complex coagulopathy
      associated with malignancy, together with the advances in our knowledge of the
      interactions of cancer with the hemostatic system. Also, to offer an update of
      the recent progresses in the risk assessment, prevention, and treatment of
      thrombohemorrhagic complications in cancer patients. RECENT FINDINGS: Mechanisms
      underlying the hemostatic derangement caused by cancer include many prothrombotic
      properties of tumor tissues. Of extreme interest are the most recent findings
      that the regulation of tumor cell hemostatic protein expression is driven by
      oncogenes, the tumor-derived tissue factor-positive microparticles are an
      important player in thrombosis, and the changes in the tumor microenvironment in
      the presence of tissue factor affect 'dormant' cells to shift to a malignant
      phenotype.On the clinical side, risk assessment models, based on clinical and
      biological risk factors, are becoming very attractive to identify categories of
      cancer patients at different thrombotic risk. Unsuspected pulmonary embolism,
      incidentally discovered, is also opening an intensive area of research. Finally,
      new updates of the guidelines to help clinicians in the management of venous
      thromboembolism in cancer patient have been recently released. SUMMARY: The
      coagulopathy of cancer is complex. Thrombotic and bleeding complications
      significantly contribute to morbidity and mortality in this disease. The accrued
      knowledge of the underlying mechanisms is helping establish more accurate and
      appropriate interventions for the management of the thrombotic risk in these
      patients.

PMID- 25054909
TI  - Understanding platelets in malaria infection.
AB  - PURPOSE OF REVIEW: Platelets are most identified as the cellular mediator of
      thrombosis. It is becoming increasingly evident that platelets also have
      complicated roles in vascular inflammatory and infectious diseases. Platelets
      have been linked to initiating or accelerating the pathogenesis of diverse
      pathologies, such as atherosclerosis acute and chronic transplant rejection,
      arthritis, influenza, and malaria infection. Platelets may also have protective
      roles in killing microbes, such as bacteria. Malaria kills over 500,000 people
      per year, so understanding the multifaceted roles for platelets in malaria
      infection is of critical importance. RECENT FINDINGS: Recent literature has on
      the surface made the role of platelets in malaria infection somewhat confusing,
      with seemingly contradictory studies indicating a protective role for platelets
      in malaria infection by direct parasite killing, although others have indicated
      that platelets have an adverse proinflammatory role. However, what can appear to
      be mechanistic discrepancies are likely best explained through a better
      understanding and appreciation of platelet immune functions, especially in the
      context of the disease outcome or model systems used. SUMMARY: In this review, we
      will first briefly highlight platelet immune cell functions. We will then discuss
      how platelet immune and inflammatory functions may affect responses to malaria
      infection in a disease outcome and animal model context.

PMID- 25054908
TI  - Global assays of hemostasis.
AB  - PURPOSE OF REVIEW: There exists an imbalance between our understanding of the
      physiology of the blood coagulation process and the translation of this
      understanding into useful assays for clinical application. As technology
      advances, the capabilities for merging the two areas have become more attainable.
      Global assays have advanced our understanding of the dynamics of the blood
      coagulation process beyond end point assays and are at the forefront of
      implementation in the clinic. RECENT FINDINGS: We will review recent advances in
      the main global assays with a focus on thrombin generation that have potential
      for clinical utility. These assays include direct (thrombogram, whole blood,
      purified systems) and indirect empirical measures of thrombin generation
      (thromboelastography) and mechanism-based computational models that use plasma
      composition data from individuals to generate thrombin generation profiles.
      SUMMARY: Empirical thrombin generation assays (direct and indirect) and
      computational modeling of thrombin generation have greatly advanced our
      understanding of the hemostatic balance. Implementation of these types of assays
      and visualization approaches in the clinic will potentially provide a basis for
      the development of individualized patient care. Advances in both empirical and
      computational global assays have made the goal of predicting precrisis changes in
      an individual's hemostatic state one step closer.

PMID- 25054911
TI  - Detection of counterfeit electronic components through ambient mass spectrometry
      and chemometrics.
AB  - In the last several years, illicit electronic components have been discovered in
      the inventories of several distributors and even installed in commercial and
      military products. Illicit or counterfeit electronic components include a broad
      category of devices that can range from the correct unit with a more recent date
      code to lower-specification or non-working systems with altered names,
      manufacturers and date codes. Current methodologies for identification of
      counterfeit electronics rely on visual microscopy by expert users and, while
      effective, are very time-consuming. Here, a plasma-based ambient
      desorption/ionization source, the flowing atmospheric pressure afterglow (FAPA)
      is used to generate a mass-spectral fingerprint from the surface of a variety of
      discrete electronic integrated circuits (ICs). Chemometric methods, specifically
      principal component analysis (PCA) and the bootstrapped error-adjusted single
      sample technique (BEAST), are used successfully to differentiate between genuine
      and counterfeit ICs. In addition, chemical and physical surface-removal
      techniques are explored and suggest which surface-altering techniques were
      utilized by counterfeiters. 

PMID- 25054910
TI  - Zebrafish as a model system for the study of hemostasis and thrombosis.
AB  - PURPOSE OF REVIEW: Although the zebrafish has been established as a research tool
      over the past two to three decades, in hematology it has primarily been used to
      investigate areas distinct from coagulation. The advantages of this vertebrate
      model include high fecundity, rapid and external development, and conservation of
      virtually all clotting factors in the zebrafish genomic sequence. Here, we
      summarize the growing application of this technology to the study of hemostasis
      and thrombosis. RECENT FINDINGS: Loss of function studies have demonstrated
      conservation of function for a number of zebrafish coagulation factors. These
      include positive and negative regulators of coagulation, as well as key
      components of the thrombus itself, such as von Willebrand factor, fibrinogen, and
      thrombocytes. Such analyses have also been leveraged to aid in the understanding
      of human variation and disease, as well as to perform in-vivo structure/function
      experiments. SUMMARY: The zebrafish is an organism that lends itself to a number
      of unique and powerful approaches not possible in mammals. This review
      demonstrates that there is a high degree of genetic and functional conservation
      of coagulation, portending future insights into hemostasis and thrombosis through
      the use of this model.

PMID- 25054912
TI  - Role of microRNA-150 and glycoprotein nonmetastatic melanoma protein B in
      angiogenesis during hyperoxia-induced neonatal lung injury.
AB  - Glycoprotein nonmetastatic melanoma protein B (GPNMB), a transmembrane protein,
      has been reported to have an important role in tissue repair and angiogenesis.
      Recently, we have demonstrated that hyperoxia exposure down-regulates microRNA
      (miR)-150 expression and concurrent induction of its target gene, GPNMB, in
      neonatal rat lungs. This study aimed to test the hypothesis that soluble GPNMB
      (sGPNMB) promotes angiogenesis in the hyperoxic neonatal lungs. Wild-type (WT) or
      miR-150 knockout (KO) neonates, exposed to 95% O2 for 3, 6, and 10 days, were
      evaluated for lung phenotypes, GPNMB protein expression in the lungs, and sGPNMB
      levels in the bronchoalveolar lavage. Angiogenic effects of sGPNMB were examined
      both in vitro and in vivo. After a 6-day exposure, similar analyses were
      performed in WT and miR-150 KO neonates during recovery at 7, 14, and 21 days.
      miR-150 KO neonates displayed an increased capillary network, decreased
      inflammation, and less alveolar damage compared with WT neonates after hyperoxia
      exposure. The early induction of GPNMB and sGPNMB were found in miR-150 KO
      neonates. The recombinant GPNMB, which contained a soluble portion of GPNMB,
      promoted endothelial tube formation in vitro and enhanced angiogenesis in vivo.
      The increased capillaries in the hyperoxic lungs of miR-150 KO neonates appeared
      dysmorphic. They were abnormally enlarged in size and occasionally laid at
      subepithelial regions in the alveoli. However, the lung architecture returned to
      normal during recovery, suggesting that abnormal vascularity during hyperoxia
      does not affect postnatal lung development. GPNMB plays an important role in
      angiogenesis during hyperoxia injury. Treatment with GPNMB may offer a novel
      therapeutic approach in reducing pathologic complications in bronchopulmonary
      dysplasia. 

PMID- 25054913
TI  - Effects of emotion regulation difficulties on the tonic and phasic cardiac
      autonomic response.
AB  - BACKGROUND: Emotion regulation theory aims to explain the interactions between
      individuals and the environment. In this context, Emotion Regulation Difficulties
      (ERD) disrupt the physiological component of emotions through the autonomic
      nervous system and are involved in several psychopathological states. OBJECTIVE:
      We were interested in comparing the influence of a film-elicited emotion
      procedure on the autonomic nervous system activity of two groups with different
      levels of emotion regulation difficulties. METHODS: A total of 63 women
      (undergraduate students) ranging from 18 to 27 (20.7 +/- 1.99) years old were
      included. Using the upper and lower quartile of a questionnaire assessing the
      daily difficulties in regulating emotions, two groups, one with low (LERD) and
      one with high (HERD) levels of emotion regulation difficulties, were constituted
      and studied during a film-elicited emotion procedure. Cardiac vagal activity (HF
      HRV) was analyzed during three periods: baseline, film-elicited emotion, and
      recovery. RESULTS: The cardiovascular results showed a decrease in HF-HRV from
      baseline to elicitation for both groups. Then, from elicitation to recovery, HF
      HRV increased for the LERD group, whereas a low HF-HRV level persisted for the
      HERD group. CONCLUSIONS: The HERD group exhibited inappropriate cardiac vagal
      recovery after a negative emotion elicitation had ended. Cardiac vagal tone took
      longer to return to its initial state in the HERD group than in the LERD group.
      Prolonged cardiac vagal suppression might constitute an early marker of emotion
      regulation difficulties leading to lower cardiac vagal tone.

PMID- 25054914
TI  - Wide impairment of cerebral serotoninergic activity but inter-individual
      heterogeneity in bulimia nervosa patients: a pilot [(18)F]MPPF/PET study.
AB  - OBJECTIVES: Bulimia nervosa (BN) is associated with abnormalities of
      serotoninergic system. Functional or ligand specific brain imaging studies
      revealed abnormalities in non-overlapping regions. [(18)F]MPPF (4-(2
      methoxyphenyl)-1-[2-(N-2-pyridinyl)-p-fluorobenzamido]-ethylpiperazine) is a
      selective 5-HT1A receptor antagonist with a serotonin-like affinity, capable to
      assess changes of brain serotoninergic activity in BN patients. METHODS:
      [(18)F]MPPF cerebral binding potential (BPND) was measured by positron emission
      tomography scan in nine purging-type BN patients and eleven age-matched controls.
      Voxel-based statistical parametric mapping (SPM) analyses were performed to
      assess BPND differences between the two groups and between each BN patient and
      controls group. RESULTS: Mean [(18)F]MPPF BPND was overall increased in BN
      patients. SPM analysis with revealed symmetrical large clusters of increased
      [(18)F]MPPF binding in insula, temporo-parietal cortex, prefrontal cortex, in
      limbic, paralimbic cortex and raphe nuclei. SPM individual analysis indicated
      significant heterogeneity of [(18)F]MPPF mapping within BN group, including cases
      with isolated up to widespread increased binding. [(18)F]MPPF BPND did not
      covariate with depression or eating behaviour-related scores. CONCLUSIONS: Large
      clusters of increased [(18)F]MPPF binding in severe BN overlap previous results,
      separately described within fMRI or PET studies. The relationship between the
      inter-individual [(18)F]MPPF binding heterogeneity and serotoninergic modulators
      efficacy in these patients remains to be assessed.

PMID- 25054915
TI  - Features and management of pyrexia with combined dabrafenib and trametinib in
      metastatic melanoma.
AB  - The combination of dabrafenib and trametinib (CombiDT) is an effective treatment
      for BRAF-mutant metastatic melanoma; however, over 70% of patients develop drug
      related pyrexia, and little is known about this toxicity. We sought to examine
      the features and management of CombiDT pyrexia. The association between pyrexia
      and patient demographics, disease characteristics and outcome variables was
      assessed in patients treated with CombiDT at a single institution. The
      clinicopathological features of pyrexic events were analysed. Fourteen of 32
      (44%) patients developed pyrexia (temperature>=38.5 degrees C). Pyrexia was
      recurrent in 11/14 (79%). The median time to pyrexia was 38 days. Pyrexia was not
      associated with age, sex nor disease burden, and did not correlate with RECIST
      response, progression-free nor overall survival. Paracetamol, NSAIDs and/or dose
      reduction (DR) were ineffective secondary prophylaxis for pyrexia, whereas
      corticosteroids were effective in all patients (n=8), including two with multiple
      previous pyrexic events despite several DRs. In patients with previous DRs who
      commenced steroids (n=3), CombiDT doses were re-escalated without pyrexia.
      Pyrexia is a frequent and recurrent toxicity with CombiDT, with no predictive
      clinical characteristics. Pyrexia does not correlate with clinical outcome.
      Neither DR nor antipyretics are effective secondary prophylaxis, whereas
      corticosteroids are effective, prevent DR and enable re-escalation of CombiDT
      dosing.

PMID- 25054916
TI  - A tri-component conservation strategy reveals highly confident microRNA-mRNA
      interactions and evolution of microRNA regulatory networks.
AB  - MicroRNAs are small non-coding RNAs that can regulate expressions of their target
      genes at the post-transcriptional level. In this study, we propose a tri
      component strategy that combines the conservation of microRNAs, homology of mRNA
      coding regions, and conserved microRNA binding sites in the 3' untranslated
      regions to discover conserved microRNA-mRNA interactions. To validate the
      performance of our conservation strategy, we collected the experimentally
      validated microRNA-mRNA interactions from three databases as the golden standard.
      We found that the proposed strategy can improve the performance of existing
      target prediction algorithms by approximately 2-4 fold. In addition, we
      demonstrated that the proposed strategy could efficiently retain highly confident
      interactions from the intersection results of the existing algorithms and filter
      out the possible false positive predictions in the union one. Furthermore, this
      strategy can facilitate our ability to trace the homologues in different species
      that are targeted by the same miRNA family because it combines these three
      features to identify the conserved miRNA-mRNA interactions during evolution.
      Through an extensive application of the proposed conservation strategy to a study
      of the miR-1/206 regulatory network, we demonstrate that the target mRNA
      recruiting process could be associated with expansion of miRNA family during its
      evolution. We also uncovered the functional evolution of the miR-1/206 regulatory
      network. In this network, the early targeted genes tend to participate in more
      general and development-related functions. In summary, the conservation strategy
      is capable of helping to highlight the highly confident miRNA-mRNA interactions
      and can be further applied to reveal the evolutionary features of miRNA
      regulatory network and functions. 

PMID- 25054917
TI  - Mechanisms of photostability in kynurenines: a joint electronic-structure and
      dynamics study.
AB  - Kynurenines are UV filters found in the human ocular lens which protect the
      retina from radiation damage. We report on ab initio investigations of the
      photochemistry of the cis and trans conformers of kynurenine and of an
      intramolecularly hydrogen-bonded conformer of 3-hydroxykynurenine O-beta-D
      glucoside. We have explored the excited-state reaction paths for several
      radiationless excited-state deactivation processes in kynurenines. We show that
      electron-driven proton-transfer processes mediated by an excited state of charge
      transfer character exhibit negligible barriers and that the relevant potential
      energy profiles are lower in energy than the lowest absorbing pipi* state. In
      these proton-transfer processes, a proton moves from one of the amino groups of
      kynurenine to the keto group. We also report on nonadiabatic trajectory-surface
      hopping molecular-dynamics simulations for photoexcited kynurenine. These
      simulations show that the cis and trans conformers of kynurenine deactivate on a
      femtosecond-to-picosecond time scale preferably via electron-driven proton
      transfer from one of the amino groups to the keto group. Cis kynurenine
      deactivates via a ring-N-H...O?C proton-transfer process. Trans kynurenine tends
      to undergo trans -> cis isomerization before deactivating via the same process.
      These results suggest that the deactivation process involving the ring-amino
      group in the cis conformer of kynurenine is the most efficient excited-state
      deactivation process in kynurenines. The joint electronic-structure calculations
      and dynamics simulations provide a new level of mechanistic insight into the
      efficient UV-filtering capacity of kynurenines.

PMID- 25054918
TI  - Microfluidic surface-enhanced Raman scattering sensor with monolithically
      integrated nanoporous gold disk arrays for rapid and label-free biomolecular
      detection.
AB  - We present a microfluidic surface-enhanced Raman scattering (SERS) sensor for
      rapid and label-free biomolecular detection. Our sensor design mitigates a common
      limiting factor in microfluidic SERS sensors that utilize integrated
      nanostructures: low-efficiency transport of biomolecules to nanostructured
      surface which adversely impacts sensitivity. Our strategy is to increase the
      total usable nanostructured surface area, which provides more adsorption sites
      for biomolecules. Specifically, a nanoporous gold disk (NPGD) array, a highly
      effective SERS substrate, has been monolithically integrated inside a
      microfluidic chip. Individual NPGD is known to feature an order of magnitude
      larger surface area than its projected disk area. The increased surface area
      arises from nanoscale pores and ligaments three-dimensionally distributed in the
      NPGD, which manifest themselves as high-density SERS hot-spots. High-density NPGD
      arrays further guarantee large coverage of these hot-spots on the microchannel
      floor. The sensor performance has been demonstrated using Rhodamine 6G to
      quantify spatial uniformity and determine the shortest detection time. Next, the
      sensor is applied to detect two biomolecules, dopamine and urea, with
      unprecedented detection limit and speed compared to other existing microfluidic
      SERS sensors. The sensor holds great promise in point-of-care applications for
      various biomolecular detections.

PMID- 25054921
TI  - Sequence, structural and expression divergence of duplicate genes in the bovine
      genome.
AB  - Gene duplication is a widespread phenomenon in genome evolution, and it has been
      proposed to serve as an engine of evolutionary innovation. In the present study,
      we performed the first comprehensive analysis of duplicate genes in the bovine
      genome. A total of 3131 putative duplicated gene pairs were identified, including
      712 cattle-specific duplicate gene pairs unevenly distributed across the genome,
      which are significantly enriched for specific biological functions including
      immunity, growth, digestion, reproduction, embryonic development, inflammatory
      response, and defense response to bacterium. Around 97.1% (87.8%) of (cattle
      specific) duplicate gene pairs were found to have distinct exon-intron
      structures. Analysis of gene expression by RNA-Seq and sequence divergence
      (synonymous or non-synonymous) revealed that expression divergence is correlated
      with sequence divergence, as has been previously observed in other species. This
      analysis also led to the identification of a subset of cattle-specific duplicate
      gene pairs exhibiting very high expression divergence. Interestingly, further
      investigation revealed a significant relationship between structural and
      expression divergence while controlling for the effect of synonymous sequence
      divergence. Together these results provide further insight into duplicate gene
      sequence and expression divergence in cattle, and their potential contributions
      to phenotypic divergence. 

PMID- 25054920
TI  - Rho GTPases in collective cell migration.
AB  - The family of Rho GTPases are intracellular signal transducers that link cell
      surface signals to multiple intracellular responses. They are best known for
      their role in regulating actin dynamics required for cell migration, but in
      addition control cell-cell adhesion, polarization, vesicle trafficking, and the
      cell cycle. The roles of Rho GTPases in single mesenchymal cell migration are
      well established and rely on Cdc42- and Rac-dependent cell protrusion of a
      leading edge, coupled to Rho-dependent contractility required to move the cell
      body forward. In cells migrating collectively, cell-cell junctions are
      maintained, and migrating leader cells are mechanically coupled to, and
      coordinate, migration with follower cells. Recent evidence suggests that Rho
      GTPases provide multifunctional input to collective cell polarization, cell-cell
      interaction, and migration. Here, we discuss the role of Rho GTPases in
      initiating and maintaining front-rear, apical-basal cell polarization,
      mechanotransduction, and cell-cell junction stability between leader and follower
      cells, and how these roles are integrated in collective migration. Thereby,
      spatiotemporal fine-tuning of Rho GTPases within the same cell and among cells in
      the cell group are crucial in controlling potentially conflicting, divergent cell
      adhesion and cytoskeletal functions to achieve supracellular coordination and
      mechanocoupling. 

PMID- 25054924
TI  - Reproducibility.

PMID- 25054922
TI  - Epigenetic alterations in the brain associated with HIV-1 infection and
      methamphetamine dependence.
AB  - HIV involvement of the CNS continues to be a significant problem despite
      successful use of combination antiretroviral therapy (cART). Drugs of abuse can
      act in concert with HIV proteins to damage glia and neurons, worsening the
      neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive
      psychostimulant drug, abuse of which has reached epidemic proportions and is
      associated with high-risk sexual behavior, increased HIV transmission, and
      development of drug resistance. HIV infection and METH dependence can have
      synergistic pathological effects, with preferential involvement of frontostriatal
      circuits. At the molecular level, epigenetic alterations have been reported for
      both HIV-1 infection and drug abuse, but the neuropathological pathways triggered
      by their combined effects are less known. We investigated epigenetic changes in
      the brain associated with HIV and METH. We analyzed postmortem frontal cortex
      tissue from 27 HIV seropositive individuals, 13 of which had a history of METH
      dependence, in comparison to 14 cases who never used METH. We detected changes in
      the expression of DNMT1, at mRNA and protein levels, that resulted in the
      increase of global DNA methylation. Genome-wide profiling of DNA methylation in a
      subset of cases, showed differential methylation on genes related to
      neurodegeneration; dopamine metabolism and transport; and oxidative
      phosphorylation. We provide evidence for the synergy of HIV and METH dependence
      on the patterns of DNA methylation on the host brain, which results in a
      distinctive landscape for the comorbid condition. Importantly, we identified new
      epigenetic targets that might aid in understanding the aggravated
      neurodegenerative, cognitive, motor and behavioral symptoms observed in persons
      living with HIV and addictions. 

PMID- 25054931
TI  - Self-assembly: phases full of fullerenes.

PMID- 25054923
TI  - Periaortic brown adipose tissue as a major determinant of [18F]
      fluorodeoxyglucose vascular uptake in atherosclerosis-prone, apoE-/- mice.
AB  - BACKGROUND: [18F]-fluorodeoxyglucose (FDG) has been suggested for the clinical
      and experimental imaging of inflammatory atherosclerotic lesions. Significant FDG
      uptake in brown adipose tissue (BAT) has been observed both in humans and mice.
      The objective of the present study was to investigate the influence of periaortic
      BAT on apolipoprotein E-deficient (apoE-/-) mouse atherosclerotic lesion imaging
      with FDG. METHODS: ApoE-/- mice (36 +/- 2 weeks-old) were injected with FDG (12
      +/- 2 MBq). Control animals (Group A, n = 7) were injected conscious and kept
      awake at room temperature (24 degrees C) throughout the accumulation period. In
      order to minimize tracer activity in periaortic BAT, Group B (n = 7) and C (n =
      6) animals were injected under anaesthesia at 37 degrees C and Group C animals
      were additionally pre-treated with propranolol. PET/CT acquisitions were
      performed prior to animal euthanasia and ex vivo analysis of FDG biodistribution.
      RESULTS: Autoradiographic imaging indicated higher FDG uptake in atherosclerotic
      lesions than in the normal aortic wall (all groups, P<0.05) and the blood (all
      groups, P<0.01) which correlated with macrophage infiltration (R = 0.47;
      P<0.001). However, periaortic BAT uptake was either significantly higher (Group
      A, P<0.05) or similar (Group B and C, P = NS) to that observed in atherosclerotic
      lesions and was shown to correlate with in vivo quantified aortic FDG activity.
      CONCLUSION: Periaortic BAT FDG uptake was identified as a confounding factor
      while using FDG for the non-invasive imaging of mouse atherosclerotic lesions.

PMID- 25054932
TI  - Asymmetric catalysis: a radical revolution in synthesis.

PMID- 25054933
TI  - C-H activation: the road less travelled to amination.

PMID- 25054934
TI  - Fluorescence microscopy: strategic blinking.

PMID- 25054935
TI  - Mimicking nature with synthetic macromolecules capable of recognition.
AB  - Nature has, through billions of years of evolution, assembled a multitude of
      polymeric macromolecules capable of exquisite molecular recognition. This
      functionality arises from the precise control exerted over their biosynthesis
      that results in key residues being anchored in the appropriate positions to
      interact with target substrates. Developing 'wholly synthetic' macromolecular
      analogues that can mimic this behaviour presents a considerable challenge to
      chemists, who lack the 'biological machinery' used in nature to assemble polymers
      with such precision. In addressing this challenge, familiar chemical concepts,
      such as combinatorial methods and supramolecular interactions, have been adapted
      for application in the macromolecular arena. Working from a limited set of
      residues, synthetic macromolecules have been produced that display surprisingly
      high binding affinities towards target proteins, even possessing useful in vivo
      activities. These observations are all the more surprising when one considers the
      heterogeneity inherent within these synthetic macromolecular receptors, and
      provoke intriguing questions regarding our assumptions about the design of
      receptors. 

PMID- 25054936
TI  - Discovery and introduction of a (3,18)-connected net as an ideal blueprint for
      the design of metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) are a promising class of porous materials because
      it is possible to mutually control their porous structure, composition and
      functionality. However, it is still a challenge to predict the network topology
      of such framework materials prior to their synthesis. Here we use a new rare
      earth (RE) nonanuclear carboxylate-based cluster as an 18-connected molecular
      building block to form a gea-MOF (gea-MOF-1) based on a (3,18)-connected net. We
      then utilized this gea net as a blueprint to design and assemble another MOF (gea
      MOF-2). In gea-MOF-2, the 18-connected RE clusters are replaced by metal-organic
      polyhedra, peripherally functionalized so as to have the same connectivity as the
      RE clusters. These metal-organic polyhedra act as supermolecular building blocks
      when they form gea-MOF-2. The discovery of a (3,18)-connected MOF followed by
      deliberate transposition of its topology to a predesigned second MOF with a
      different chemical system validates the prospective rational design of MOFs. 

PMID- 25054937
TI  - A spontaneously blinking fluorophore based on intramolecular spirocyclization for
      live-cell super-resolution imaging.
AB  - Single-molecule localization microscopy is used to construct super-resolution
      images, but generally requires prior intense laser irradiation and in some cases
      additives, such as thiols, to induce on-off switching of fluorophores. These
      requirements limit the potential applications of this methodology. Here, we
      report a first-in-class spontaneously blinking fluorophore based on an
      intramolecular spirocyclization reaction. Optimization of the intramolecular
      nucleophile and rhodamine-based fluorophore (electrophile) provide a suitable
      lifetime for the fluorescent open form, and equilibrium between the open form and
      the non-fluorescent closed form. We show that this spontaneously blinking
      fluorophore is suitable for single-molecule localization microscopy imaging deep
      inside cells and for tracking the motion of structures in living cells. We
      further demonstrate the advantages of this fluorophore over existing
      methodologies by applying it to nuclear pore structures located far above the
      coverslip with a spinning-disk confocal microscope and for repetitive time-lapse
      super-resolution imaging of microtubules in live cells for up to 1 h.

PMID- 25054938
TI  - Directed assembly of optoelectronically active alkyl-pi-conjugated molecules by
      adding n-alkanes or pi-conjugated species.
AB  - Supramolecular assembly can yield ordered structures by taking advantage of the
      cumulative effect of multiple non-covalent interactions between adjacent
      molecules. The thermodynamic origin of many self-assembled structures in water is
      the balance between the hydrophilic and hydrophobic segments of the molecule.
      Here, we show that this approach can be generalized to use solvophobic and
      solvophilic segments of fully hydrophobic alkylated fullerene molecules. Addition
      of n-alkanes results in their assembly--due to the antipathy of C60 towards n
      alkanes--into micelles and hexagonally packed gel-fibres containing insulated C60
      nanowires. The addition of pristine C60 instead directs the assembly into
      lamellar mesophases by increasing the proportion of pi-conjugated material in the
      mixture. The assembled structures contain a large fraction of optoelectronically
      active material and exhibit comparably high photoconductivities. This method is
      shown to be applicable to several alkyl-pi-conjugated molecules, and can be used
      to construct organized functional materials with pi-conjugated sections.

PMID- 25054939
TI  - Direct observation of the collapse of the delocalized excess electron in water.
AB  - It is generally assumed that the hydrated electron occupies a quasi-spherical
      cavity surrounded by only a few water molecules in its equilibrated state.
      However, in the very moment of its generation, before water has had time to
      respond to the extra charge, it is expected to be significantly larger in size.
      According to a particle-in-a-box picture, the frequency of its absorption
      spectrum is a sensitive measure of the initial size of the electronic
      wavefunction. Here, using transient terahertz spectroscopy, we show that the
      excess electron initially absorbs in the far-infrared at a frequency for which
      accompanying ab initio molecular dynamics simulations estimate an initial
      delocalization length of ~ 40 A. The electron subsequently shrinks due to
      solvation and thereby leaves the terahertz observation window very quickly,
      within ~ 200 fs.

PMID- 25054940
TI  - An organic thiyl radical catalyst for enantioselective cyclization.
AB  - A diverse array of chiral organocatalysts have been developed that rely on acid
      base interactions to promote enantioselective ionic reactions via the movement of
      electron pairs. The stereocontrol of radical reactions using organocatalysts is
      an alternative approach, and several studies have shown that synthetically useful
      reactivity can result by controlling the movement of single electrons. However,
      in these studies, it is still an acid-based organocatalyst which forms a closed
      shell intermediate with substrate prior to the radical reaction and imparts
      chiral information, and use of a chiral organic radical directly as catalyst has
      only rarely been explored. Here, we report the design of an organic thiyl radical
      catalyst with a carefully designed chiral pocket constructed around a chiral
      thiol precatalyst. The resulting catalyst was used to effect highly diastereo-
      and enantioselective C-C bond-forming radical cyclizations. 

PMID- 25054941
TI  - Vibronic coherence in oxygenic photosynthesis.
AB  - Photosynthesis powers life on our planet. The basic photosynthetic architecture
      consists of antenna complexes that harvest solar energy and reaction centres that
      convert the energy into stable separated charge. In oxygenic photosynthesis, the
      initial charge separation occurs in the photosystem II reaction centre, the only
      known natural enzyme that uses solar energy to split water. Both energy transfer
      and charge separation in photosynthesis are rapid events with high quantum
      efficiencies. In recent nonlinear spectroscopic experiments, long-lived
      coherences have been observed in photosynthetic antenna complexes, and
      theoretical work suggests that they reflect underlying electronic-vibrational
      resonances, which may play a functional role in enhancing energy transfer. Here,
      we report the observation of coherent dynamics persisting on a picosecond
      timescale at 77 K in the photosystem II reaction centre using two-dimensional
      electronic spectroscopy. Supporting simulations suggest that the coherences are
      of a mixed electronic-vibrational (vibronic) nature and may enhance the rate of
      charge separation in oxygenic photosynthesis.

PMID- 25054942
TI  - Controlling epithelial sodium channels with light using photoswitchable
      amilorides.
AB  - Amiloride is a widely used diuretic that blocks epithelial sodium channels
      (ENaCs). These heterotrimeric transmembrane proteins, assembled from beta, gamma
      and alpha or delta subunits, effectively control water transport across epithelia
      and sodium influx into non-epithelial cells. The functional role of
      deltabetagammaENaC in various organs, including the human brain, is still poorly
      understood and no pharmacological tools are available for the functional
      differentiation between alpha- and delta-containing ENaCs. Here we report several
      photoswitchable versions of amiloride. One compound, termed PA1, enables the
      optical control of ENaC channels, in particular the deltabetagamma isoform, by
      switching between blue and green light, or by turning on and off blue light. PA1
      was used to modify functionally deltabetagammaENaC in amphibian and mammalian
      cells. We also show that PA1 can be used to differentiate between
      deltabetagammaENaC and alphabetagammaENaC in a model for the human lung
      epithelium. 

PMID- 25054943
TI  - The direct anti-Markovnikov addition of mineral acids to styrenes.
AB  - The direct anti-Markovnikov addition of strong Bronsted acids to alkenes remains
      an unsolved problem in synthetic chemistry. Here, we report an efficient organic
      photoredox catalyst system for the addition of HCl, HF and also phosphoric and
      sulfonic acids to alkenes, with complete regioselectivity. These transformations
      were developed using a photoredox catalyst in conjunction with a redox-active
      hydrogen atom donor. The nucleophile counterion plays a critical role by ensuring
      high reactivity, with 2,6-lutidinium salts typically furnishing the best results.
      The nature of the redox-active hydrogen atom donor is also consequential, with 4
      methoxythiophenol providing the best reactivity when 2,6-lutidinium salts are
      used. A novel acridinium sensitizer provides enhanced reactivity within several
      of the more challenging reaction manifolds. This Article demonstrates how
      nucleophilic addition reactions mediated by photoredox catalysis can change the
      way electrophilic and homofugal precursors are constructed. 

PMID- 25054944
TI  - Observation of an all-boron fullerene.
AB  - After the discovery of fullerene-C60, it took almost two decades for the
      possibility of boron-based fullerene structures to be considered. So far, there
      has been no experimental evidence for these nanostructures, in spite of the
      progress made in theoretical investigations of their structure and bonding. Here
      we report the observation, by photoelectron spectroscopy, of an all-boron
      fullerene-like cage cluster at B40(-) with an extremely low electron-binding
      energy. Theoretical calculations show that this arises from a cage structure with
      a large energy gap, but that a quasi-planar isomer of B40(-) with two adjacent
      hexagonal holes is slightly more stable than the fullerene structure. In
      contrast, for neutral B40 the fullerene-like cage is calculated to be the most
      stable structure. The surface of the all-boron fullerene, bonded uniformly via
      delocalized sigma and pi bonds, is not perfectly smooth and exhibits unusual
      heptagonal faces, in contrast to C60 fullerene. 

PMID- 25054945
TI  - Mass-selected nanoparticles of PtxY as model catalysts for oxygen
      electroreduction.
AB  - Low-temperature fuel cells are limited by the oxygen reduction reaction, and
      their widespread implementation in automotive vehicles is hindered by the cost of
      platinum, currently the best-known catalyst for reducing oxygen in terms of both
      activity and stability. One solution is to decrease the amount of platinum
      required, for example by alloying, but without detrimentally affecting its
      properties. The alloy PtxY is known to be active and stable, but its synthesis in
      nanoparticulate form has proved challenging, which limits its further study.
      Herein we demonstrate the synthesis, characterization and catalyst testing of
      model PtxY nanoparticles prepared through the gas-aggregation technique. The
      catalysts reported here are highly active, with a mass activity of up to 3.05 A
      mgPt(-1) at 0.9 V versus a reversible hydrogen electrode. Using a variety of
      characterization techniques, we show that the enhanced activity of PtxY over
      elemental platinum results exclusively from a compressive strain exerted on the
      platinum surface atoms by the alloy core.

PMID- 25054946
TI  - Cooperative activation of cyclobutanones and olefins leads to bridged ring
      systems by a catalytic [4 + 2] coupling.
AB  - Bridged ring systems are widely found in natural products, and successful
      syntheses of them frequently feature intramolecular Diels-Alder reactions. These
      reactions are subclassified as either type I or type II depending on how the
      diene motif is tethered to the rest of the substrate (type I are tethered at the
      1-position of the diene and type II at the 2-position). Although the type I
      reaction has been used with great success, the molecular scaffolds accessible by
      the type II reactions are limited by the strain inherent in the formation of an
      sp(2) carbon at a bridgehead position. Here, we describe a complementary approach
      that provides access to these structures through the C-C activation of
      cyclobutanones and their coupling with olefins. Various alkenes have been coupled
      with cyclobutanones to provide a range of bridged skeletons. The ketone group of
      the products serves as a convenient handle for downstream functionalization. 

PMID- 25054948
TI  - Made by molybdenum.

PMID- 25054949
TI  - Bisphosphonate therapy for osteogenesis imperfecta.
AB  - BACKGROUND: Osteogenesis imperfecta is caused by a genetic defect resulting in an
      abnormal type I collagen bone matrix which typically results in multiple
      fractures with little or no trauma. Bisphosphonates are used in an attempt to
      increase bone mineral density and reduce these fractures in people with
      osteogenesis imperfecta. OBJECTIVES: To assess the effectiveness and safety of
      bisphosphonates in increasing bone mineral density, reducing fractures and
      improving clinical function in people with osteogenesis imperfecta. SEARCH
      METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Inborn Errors of Metabolism Trials Register which comprises references identified
      from comprehensive electronic database searches, handsearches of journals and
      conference proceedings. We additionally searched PubMed and major conference
      proceedings.Date of the most recent search: 07 April 2014. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials comparing bisphosphonates to
      placebo, no treatment, or comparator interventions in all types of osteogenesis
      imperfecta. DATA COLLECTION AND ANALYSIS: Two authors independently extracted
      data and assessed the risk of bias of the included trials. MAIN RESULTS: Fourteen
      trials (819 participants) were included. Overall, the trials were mainly at a low
      risk of bias, although selective reporting was an issue in several of the trials.
      Data for oral bisphosphonates versus placebo could not be aggregated; a
      statistically significant difference favouring oral bisphosphonates in fracture
      risk reduction and number of fractures was noted in two trials. No differences
      were reported in the remaining three trials which commented on fracture
      incidence. Five trials reported data for spine bone mineral density; all found
      statistically significant increased lumbar spine density z scores for at least
      one time point studied. For intravenous bisphosphonates versus placebo,
      aggregated data from two trials showed no statistically significant difference
      for the number of participants with at least one fracture, risk ratio 0.56 (95%
      confidence interval 0.30 to 1.06). In the remaining trial no statistically
      significant difference was noted in fracture incidence. For spine bone mineral
      density, no statistically significant difference was noted in the aggregated data
      from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43).
      In the remaining trial a statistically significant difference in mean per cent
      change in spine bone mineral density z score favoured intravenous bisphosphonates
      at six and 12 months. Data describing growth, bone pain, and functional outcomes
      after oral or intravenous bisphosphonate therapy, or both, as compared to placebo
      were incomplete among all studies, but do not show consistent improvements in
      these outcomes. Two studies compared different doses of bisphosphonates. No
      differences were found between doses when bone mineral density, fractures, and
      height or length z score were assessed. One study compared oral versus
      intravenous bisphosphonates and found no differences in primary outcomes. Two
      studies compared the intravenous bisphosphonates zoledronic acid and pamidronate.
      There were no significant differences in primary outcome. However, the studies
      were at odds as to the relative benefit of zoledronic acid over pamidronate for
      lumbosacral bone mineral density at 12 months. AUTHORS' CONCLUSIONS:
      Bisphophonates are commonly prescribed to individuals with osteogenesis
      imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous
      bisphosphonates increase bone mineral density in children and adults with this
      condition. These were not shown to be different in their ability to increase bone
      mineral density. It is unclear whether oral or intravenous bisphosphonate
      treatment consistently decreases fractures, though multiple studies report this
      independently and no studies report an increased fracture rate with treatment.
      The studies included here do not show bisphosphonates conclusively improve
      clinical status (reduce pain; improve growth and functional mobility) in people
      with osteogenesis imperfecta. Given their current widespread and expected
      continued use, the optimal method, duration of therapy and long-term safety of
      bisphosphonate therapy require further investigation. In addition, attention
      should be given to long-term fracture reduction and improvement in quality of
      life indicators.

PMID- 25054950
TI  - Statins for children with familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia is one of the most common inherited
      metabolic diseases; the average worldwide prevalence of heterozygous familial
      hypercholesterolemia is at least 1 in 500. Diagnosis of familial
      hypercholesterolemia in children is based on highly elevated low-density
      lipoprotein (LDL) cholesterol level or DNA-based analysis, or both. Coronary
      atherosclerosis has been detected in men with heterozygous familial
      hypercholesterolemia as young as 17 years old and in women with heterozygous
      familial hypercholesterolemia at 25 years old. Since the clinical complications
      of atherosclerosis occur prematurely, especially in men, lifelong hypolipidemic
      measures, started in childhood, are needed to reduce the risk of cardiovascular
      disease. In children with familial hypercholesterolemia, diet is as yet the
      cornerstone of treatment. Anion exchange resins, such as cholestyramine and
      colestipol, have also been found to be effective, but are poorly tolerated. Since
      the 1990s statin studies have been carried out among children with familial
      hypercholesterolemia (aged 7 to 17 years). Statins greatly reduced their serum
      LDL cholesterol levels. Even though statins seem to be safe and well-tolerated in
      children, their long-term safety in this age group is not firmly established.
      OBJECTIVES: To assess the effectiveness and safety of statins in children with
      familial hypercholesterolemia. SEARCH METHODS: Relevant studies were identified
      from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of
      most recent search: 14 October 2013. SELECTION CRITERIA: Randomized and
      controlled clinical studies including participants up to 18 years old, comparing
      a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed studies for inclusion and extracted data. MAIN RESULTS: We
      found 21 potentially eligible studies, of which we included eight randomized
      placebo-controlled studies (1074 participants). In general, the intervention and
      follow-up time was short (median 24 weeks; range from six weeks to two years).
      Statins reduced the mean LDL cholesterol concentration at all time points. Serum
      aspartate and alanine aminotransferase, as well as creatinine kinase
      concentrations, did not differ between treated and placebo groups at any time
      point. The risks of myopathy and clinical adverse events were very low and also
      similar in both groups. In one study simvastatin was shown to improve flow
      mediated dilatation of the brachial artery, and in another study treatment with
      pravastatin for two years induced a significant regression in carotid intima
      media thickness. AUTHORS' CONCLUSIONS: Statin treatment is an efficient lipid
      lowering therapy in children with familial hypercholesterolemia. No significant
      safety issues were identified. Statin treatment seems to be safe in the short
      term, but long-term safety is unknown. Children treated with statins should be
      carefully monitored and followed up by their pediatricians or physicians into
      adulthood. Large long-term randomized controlled trials are needed to establish
      the long-term safety issues of statins.

PMID- 25054951
TI  - [Evolution of peripartal hysterectomy at our department - five years
      evaluations].
AB  - The purpose of this study was to determine the frequency, indications,
      complications and risk factors associated with peripartum hysterectomy carried
      out at our clinical department between 1st January 2008 and 31th December 2012.
      Peripartum hysterectomy was defined as a hysterectomy performed less than 48
      hours after delivery. Clinical characteristic and obstetric histories were
      retrospectively reviewed between 5 years. There were 20 emergency peripartum
      hysterectomies among 13 660 deliveries at our department. The overall rate of
      peripartum hysterectomy was 1,46 per 1000 deliveries. The primary indications for
      hysterectomy were uncontrolled bleeding caused by uterine hypotony (45%),
      followed by placenta praevia (25%). Other indications were placental abruption
      (15%), pelvic endometriosis (5%), placenta increta (5%) and uterus myomatosus (5
      %). The incidence of peripartum hysterectomy increased 2-fold in cases of
      placental patology, and 17-fold in cases of uterine hypotony. Overall, 95% of
      hysterectomy patients required transfusions.

PMID- 25054953
TI  - Sclerosis tuberosa and pregnancy.
AB  - OBJECTIVE: To perform a review of Tuberous sclerosis complex and its
      complications during the pregnancy from up to date scientific literature. DESIGN:
      Complex systematic review of the literature. SETTING: 2nd Department of
      Obstetrics and Gynaecology, University Hospital Bratislava, Comenius University,
      Bratislava, Slovak Republic. METHODS: Complex analysis of the syndrome,
      systematic search of MEDLINE and Slovak Medical Library. The reason to create a
      complex review of this syndrome was our clinical experience with one of the most
      acute lifethreatening condition of this syndrome - acute retroperitoneal
      haemorrhage in the pregnancy. CONCLUSION: Tuberous sclerosis can cause a rare,
      but potentially lifethreatening complications, especially during the pregnancy.
      These should be carefully dispesarized and in complicated cases acute radical
      management should be considered.

PMID- 25054952
TI  - [Hormonal replacement therapy by patientsafter treatment for gynecological
      cancer].
AB  - OBJECTIVE: The most of gynecological cancers are diagnosed in postmenopausal
      period. There are, however, part of the premenopausal women which occurs to
      develop vegetative problems after medical procedures. The aim of the study is to
      provide an overview of the current status and views on hormone replacement
      therapy in women after treatment for gynecologic malignancy. SUBJECT: Systematic
      review. METHODS: Current literature review. CONCLUSION: The available literature
      sources don't show that hormone replacement therapy for premenopausal women
      worsens the prognosis of the underlying disease after treatment of gynecological
      cancer. The limiting factor in most of the works are small groups of patients and
      the low stage of disease at enrollment (especially for endometrial cancer). Even
      though no study has shown worsening prognosis or shorter disease free interval.
      However, it is necessary to proceed individually for each patient with an
      evaluation of the current status and potential benefits that this treatment can
      get.

PMID- 25054954
TI  - [Thrombotic microangiopathy in pregnancy complicated by acute hemorrhagic
      necrotic pancreatitis during early puerperium].
AB  - OBJECTIVE: Authors in the article describe a case of a patient with thrombotic
      thrombocytopenic purpurain 37 weeks gestation complicated by acute severe
      hemorrhagic-necrotic pancreatitis during the early puerperium. DESIGN: Case
      report. SETTING: Ist Department of gynaecology and obstetrics of the Comenius
      University Bratislava. CASE-REPORT: 33-years-old patient in the 37 weeks
      gestation was admitted to our department with the signs of HELLP syndrome
      (hemolysis, elevated liver enzymes, low platelets). Due to the worsening clinical
      status, we have performed caesarean section. After the transient stabilization of
      the patient's clinical status, the hemolysis with severe thrombocytopenia
      reappeared. Based on the clinical signs of abdominal pain and computer
      tomography, the diagnosis of acute hemorrhagic-necrotic pancreatitis was set. The
      primary diagnosis was thrombotic thrombocytopenic purpura. Therefore, therapeutic
      plasma exchange was performed with consequent improvement of the patients
      clinical state. Normalization of the platelet count was achieved after 4.plasma
      exchanges. Consequently 5 plasma exchanges were performed. However, one month
      later, the disease relapsed. Therapeutic plasma exchanges were needed again (4x),
      with anti CD 20 administration. This therapy had good clinical outcome, without
      the need for further plasma exchanges. CONCLUSION: Thrombotic thrombocytopenic
      purpura is highly lethal disease. Early diagnosis, treatment, and
      multidisciplinary approach are essential.

PMID- 25054955
TI  - [Prenatal diagnosis of skeletal dysplasia in first trimester of pregnancy X
      linked dominant chondrodysplasia punctata].
AB  - Case report describes successful prenatal diagnosis of skeletal dysplasia in the
      first trimester of pregnancy in a female patient affected with X-linked dominat
      chondrodysplasia punctata (CDPX2). Her first pregnancy was terminated in the
      second trimester due to skeletal dysplasia of the foetus. The diagnosis in the
      following pregnancy was finished in the first trimester - before the end of the
      13th gestational week. The diagnosis was established on the basis of
      ultrasonographic (US) examination and mutation analysis of the EBP gene in the
      material of chorionic villus sampling (CVS).

PMID- 25054956
TI  - [The INKA Program - "tailor-made" obstetric analgesia].
AB  - SETTING: Department of Obsterics and Gynecology 1st Faculty of Medicine, Charles
      University and General Faculty Hospital in Prague. OBJECTIVE: Predicting both the
      course of childbirth and the intensity of pain felt during childbirth is
      difficult, especially with first-time mothers. Some women tolerate birthing pains
      well, others require effective pain relief. Sometimes simple methods are enough,
      such as the presence of a partner, a relaxing atmosphere, massages, or walking,
      while other times the services of a birthing assistant or physician or even an
      anaesthesiologist are required. Choosing the right approach or methods should
      always be dependent on the actual situation and the individual choices and
      preferences of the mother. In line with this, the INKA Program was initiated in
      the Czech Republic in 2013. The name is an acronym derived from the Czech words
      for informed (as in the expectant mother), choice (of services), quality (of
      services offered) and analysis (of the system of care offered). The aim of this
      program is to distribute information about current possibilities for decreasing
      the pain of childbirth to the widest possible population of expectant mothers.
      The information must be objective and clearly explain the benefits and risks of
      each analgesic method, and must not encourage or discourage any particular
      method. As part of this program, a brochure titled "Birth doesnt have to be that
      painful" was distributed at the end of 2013, to inform the lay public about all
      available methods of analgesia for childbirth in the Czech Republic. The contents
      of the brochure were approved by the Czech Gynecological and Obstetrical Society
      and the Czech Society of Anaesthesiology and Intensive Care Medicine. The INKA
      program encourages the personnel of birthing centres to arrange the most
      individual approaches possible for the needs of each expectant mother. Even women
      that originally had negative attitudes toward obstetric analgesics should have
      the opportunity for adequate and effective help at any time, if the birth does
      not proceed according to their original expectations.

PMID- 25054957
TI  - [Why do we still hesitate to accept the new international criteria for the
      diagnosis of gestational diabetes mellitus? The current screening is non-uniform
      and does not correspond with evidence-based medicine].
AB  - Gestational diabetes mellitus (GDM) is the most common internal complication in
      pregnancy and similarly as the frequency of Type 2 diabetes rises in general
      population so does the frequency of GDM. The causes include unhealthy life style,
      growing incidence of overweight and obesity as well as older age of pregnant
      women. Older data reported the frequency of GDM in 3-4% of all pregnancies in the
      Czech Republic, whereas nowadays its frequency with using the same diagnostic
      criteria is more than two times higher. If we include the measurement of glycemia
      in 1 hour of oGTT, the frequency of GDM reaches more than 20%. In case we accept
      the new recommendation of the International Association for Diabetes in Pregnancy
      Study Groups (IADPSG), it is expected that the frequency of GDM will be even
      higher. IADPSG recommendation resulted from HAPO study (Hyperglycemia and Adverse
      Pregnancy Outcomes), a large international observational study on the
      relationship between mild hyperglycemia and pregnancy outcomes. Adoption of these
      new criteria is intensively discussed among experts all over the world. WHO
      adopted the IADPSG criteria in 2013. The Czech Diabetes Society committee adopted
      them in April 2014. Any official statement about the new criteria has not yet
      been issued by the Czech Gynecology and Obstetrics Society. This article analyzes
      the old and the new diagnostic criteria, summarizes the most common arguments in
      favor and against the IADPSG thresholds and tries to open the discussion about
      this important topic.

PMID- 25054958
TI  - [The alarming incidence of gestational diabetes mellitus using currently used and
      new international diagnostic criteria].
AB  - OBJECTIVE: The aim of our study was to analyze the results of oral glucose
      tolerant test (oGTT) of pregnant woman with currently used Czech criteria for
      diagnosis of GDM, to find out the prevalence of GDM if the measurement of
      glycemia in 1 hour of oGTT is included and to compare the prevalence of GDM using
      the new IADPSG (International Association of Diabetes and Pregnancy Study Groups)
      criteria versus the currently used Czech criteria. DESIGN: Retrospective
      analysis. SETTINGS: Department of Obstetrics and Gynecology of the First Faculty
      of Medicine and General Teaching Hospital, Prague. METHODS: Data from the
      standard 75g 2-hour oral glucose tolerance test (oGTT) of 2567 pregnant females
      were analyzed using the currently recommended Czech cut-off values for plasma
      glucose at baseline and at2 hours of oGTT (5.6 and 7.7 mmol/l) and at baseline, 1
      and2 hours oGTT (5.6, 8.9 and 7.7 mmol/l). The frequency of GDM using the Czech
      criteria was compared with the frequency of GDM using the novel IADPSG criteria
      (5.1, 10.0 and 8.5 mmol/l). Statistical analysis was done using the software GNU
      PSPP Statistical Analysis Software version 0.8.0-g0ad9f6. RESULTS: When using the
      current Czech criteria (at baseline and 2 hours of oGTT) GDM was diagnosed in 362
      (14.11%) females. Inclusion of glycemia at 1 hour of oGTT increased the frequency
      of GDM to 571 (22.26%) females (p<0.00). With the novel IADPSG criteria GDM was
      diagnosed in 818 (31.89%) females (p=0.038). 503 females i.e. 19.61% and 394
      females i.e. 15.36% (when glycemia at 1 h of oGTT included) respectively met the
      IADPSG but not the Czech criteria and thus were not treated for GDM. In contrast,
      47 (1.83%) resp. 147 (5.73%) of tested women who met the Czech but not the IADPSG
      criteria received unnecessary diabetes treatment. CONCLUSION: The frequency of
      GDM is higher with the novel IADPSG criteria when compared with the currently
      used Czech recommendation. Switching to IADPSG criteria might help unravel
      hitherto unidentified cases of GDM and thus improve outcomes for females with GDM
      and their offsprings.

PMID- 25054959
TI  - [HELLP syndrome complicated by liver rupture - case report].
AB  - OBJECTIVE: A case of HELLP syndrome complicated by liver rupture in the 36th week
      of pregnancy. DESIGNS: A case report. SETTING: Department of Obstetrics and
      Gynaecology, FN Olomouc. CASE REPORT: The authors report a case of 31 years old
      female patient who came to the hospital at 36th week of pregnancy with epigastric
      pain lasting about 14 days. The problems became worse in the last 10 hours. At
      admission, the patient was pale with repeatedly unmeasurable blood pressure, and
      she had lower limbs oedema. There was performed the caesarian section, during the
      operation the liver rupture was found. Both, patient and her baby, was saved
      thanks to the concerted interdisciplinary team work. CONCLUSION: One of the most
      serious complications of HELLP syndrome is liver rupture. It occurs in 3.8% of
      HELLP syndrome cases. The solution of this complication is to perform an acute
      operation. The operation is based on liver suture with application of deep
      mattress suture, applying hemostatic materials, liver compression by Mikulicz's
      tamponade or ligation of liver artery. There is also possibility to use
      omentoplasty. If there is necessity of liver resection for necrotic focus, the
      argon coagulative laser is used preferably.

PMID- 25054960
TI  - [Importance of outpatient ultrasonografically guided transvaginal
      hydrolaparoscopy in the decision algorithm of care for the infertile couple.The
      results of the Centre for Assisted Reproduction Gennet Liberec 2012--2013].
AB  - OBJECTIVE: Evaluation of the benefits of outpatient ultrasonografically guided
      transvaginal hydrolaparoscopy (UTHL) in the decision algorithm of care for the
      infertile couple. DESIGN: A retrospective study. METHODS: Impact results of UTHL
      on the management of sterility treatment at 532 IVF center clients in the period
      between 1. 8. 2012 and 31. 12. 2013. RESULTS: Physiological result was found in
      46 cases (8.64%). Absolute tubal factor was confirmedat 56 cases (10.52%) - it
      means fluid absence in CD, relative tubal factor in 208 cases (39.09%),
      endometriosis in 159 cases (29.88%), adhesions in the abdominal cavity in 188
      cases (35.33%), synechia of the cervix and/or in the uterine cavity in 35 cases
      (6.57%), polyp of cervix and/or in the uterine cavity in 38 cases (7.14%),
      hydrosalpinx in 31 cases (5.82%) , uterine anomalies in 17 cases (3.19%), myoma
      in 12 cases (2.25%) and tubal cysts at 5 cases (0.9%). 11 woman (2.06%) had
      adhesiones in places of punction in case we did not continue the operation.
      Complications have occurred in a total of 3 cases, one perforation of the uterine
      cavity and two women needed ATB therapy for infection (parametritis). One of them
      was admitted for one day observation. CONCLUSION: Minimally invasive procedure at
      one day surgery enables comprehensive diagnosis and individualizing of
      therapeutic procedure in the treatment of infertility without delay and at with
      high degree of safety for the client.

PMID- 25054961
TI  - [Diagnostic algorithm in pregnancies of uncertain viability or unknown location -
      a review of the latest recommendations].
AB  - Based on current knowledge the criteria for diagnosing nonviability in early
      intrauterine pregnancy and diagnostic algorithm in pregnancies of unknown
      location have changed. For either an intrauterine pregnancy of uncertain
      viability or a pregnancy of unknown location, the consequences of false positive
      diagnosis of nonviability or false negative diagnosis of ectopic pregnancy may be
      dire: harming of a potentially normal intrauterine pregnancy or a life
      threatening rupture from tubal pregnancy. This review aims to present the most
      important results of current studies on this topic with their recommendations and
      to improve patient care reducing the risk of inadvertent harm to potentially
      normal pregnancies.

PMID- 25054962
TI  - [Myo-inositol in the treatment of polycystic ovary syndrome].
AB  - OBJECTIVE: Presentation of a comprehensive body of knowledge on the role of
      insulin sensitizer myo-inositol in the treatment of polycystic ovary syndrome
      (PCOS). DESIGN: Review article. SETTING: Institute for the Care of Mother and
      Child, Prague. METHOD: An overview of publishing data. RESULTS AND CONCLUSION:
      Polycystic ovary syndrome is the most common cause of ovarian dysfunction and
      anovulatory infertility in women. The insulin resistance occurs very frequently
      as a part of PCOS. This paper reviews the literature documenting the
      effectiveness of insulin sensitizer myo-inositol in the treatment of ovarian
      dysfunction, symptoms of hyperandrogenism and wide complex of symptoms of
      metabolic syndrome. Six randomized controlled trials provides evidence of a
      positive effect of myo-inositol to normalize ovarian function, improve laboratory
      and clinical manifestations of hyperandrogenism and insulin resistance. The myo
      inositol treatment has been demonstrated as a safe method of PCOS management.

PMID- 25054963
TI  - Therapeutic effect of folate-targeted and PEGylated phytosomes loaded with a
      mitomycin C-soybean phosphatidyhlcholine complex.
AB  - A mitomycin C (MMC)-soybean phosphatidyhlcholine complex loaded in phytosomes was
      previously reported for the purpose of developing a MMC drug delivery system
      (Mol. Pharmaceutics 2013, 10, 90-101), but this approach was limited by rapid
      elimination from the body and lack of target specificity. In this article, to
      overcome these limitations, MMC-soybean phosphatidyhlcholine complex-loaded
      phytosomes (MMC-loaded phytosomes) as drug carriers were surface-functionalized
      with folate-PEG (FA-PEG) to achieve reduced toxicity and a superior MMC-mediated
      therapeutic effect. For this purpose, FA was conjugated to DSPE-PEG-NH2, and the
      resultant DSPE-PEG-FA was introduced into the lipid moiety of the phytosomes via
      a postinsertion technique. The prepared FA-PEG-functionalized MMC-loaded
      phytosomes (FA-PEG-MMC-loaded phytosomes) have a particle size of 201.9 +/- 2.4
      nm, a PDI of 0.143 +/- 0.010, a zeta potential of -27.50 +/- 1.67 mV, a spherical
      shape, and sustained drug release. The remarkable features of FA-PEG-MMC-loaded
      phytosomes included increased cellular uptake in HeLa cells and higher
      accumulation in H22 tumor-bearing mice over that of the PEG-MMC-loaded
      phytosomes. Furthermore, FA-PEG-MMC-loaded phytosomes were associated with
      enhanced cytotoxic activity in vitro and an improved antitumor effect in vivo
      compared to that resulting from free MMC injection. These results suggest that FA
      PEG-MMC-loaded phytosomes may be useful drug delivery systems for widening the
      therapeutic window of MMC in clinical trials. 

PMID- 25054965
TI  - Relationship between lower-limb muscle strength and functional independence among
      elderly people according to frailty criteria: a cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: Muscle strength and functional independence are considered
      to be determinants of frailty levels among elderly people. The aim here was to
      compare lower-limb muscle strength (LLMS) with functional independence in
      relation to sex, age and number of frailty criteria, and to ascertain the
      influence of these variables on elderly outpatients' independence. DESIGN AND
      SETTING: Quantitative cross-sectional study, in a tertiary hospital. METHODS: The
      study was conducted on 150 elderly outpatients of both sexes who were in a
      cognitive condition allowing oral communication, between October 2005 and October
      2007. The following instruments were used: five-times sit-to-stand test (FTSST),
      Functional Independence Measurement (FIM) and Lawton's Instrumental Activities of
      Daily Living Scale (IADL). Descriptive, comparative, multivariate, univariate and
      Cronbach alpha analyses were performed. RESULTS: The mean time taken in the FTSST
      was 21.7 seconds; the mean score for FIM was 82.2 and for IADL was 21.2; 44.7% of
      the subjects presented 1-2 frailty criteria and 55.3% > 3 criteria. There was a
      significant association between LLMS and functional independence in relation to
      the number of frailty criteria, without homogeneity regarding sex and age.
      Functional independence showed significant influence from sex and LLMS.
      CONCLUSION: Elderly individuals with 1 or 2 frailty criteria presented greater
      independence in all FTSST scores. The subjects with higher LLMS presented better
      functional independence.

PMID- 25054964
TI  - Two structurally different dienelactone hydrolases (TfdEI and TfdEII) from
      Cupriavidus necator JMP134 plasmid pJP4 catalyse cis- and trans-dienelactones
      with similar efficiency.
AB  - In this study, dienelactone hydrolases (TfdEI and TfdEII) located on plasmid pJP4
      of Cupriavidus necator JMP134 were cloned, purified, characterized and three
      dimensional structures were predicted. tfdEI and tfdEII genes were cloned into
      pET21b vector and expressed in E. coli BL21(DE3). The enzymes were purified by
      applying ultra-membrane filtration, anion-exchange QFF and gel-filtration
      columns. The enzyme activity was determined by using cis-dienelactone. The three
      dimensional structure of enzymes was predicted using SWISS-MODEL workspace and
      the biophysical properties were determined on ExPASy server. Both TfdEI and
      TfdEII (Mr 25 kDa) exhibited optimum activity at 37 degrees C and pH 7.0. The
      enzymes retained approximately 50% of their activity after 1 h of incubation at
      50 degrees C and showed high stability against denaturing agents. The TfdEI and
      TfdEII hydrolysed cis-dienelactone at a rate of 0.258 and 0.182 uMs(-1), with a
      Km value of 87 uM and 305 uM, respectively. Also, TfdEI and TfdEII hydrolysed
      trans-dienelactone at a rate of 0.053 uMs(-1) and 0.0766 uMs(-1), with a Km value
      of 84 uM and 178 uM, respectively. The TfdEI and TfdEII kcat/Km ratios were 0.12
      uM(-1) s(-1) and 0.13 uM(-1) s(-1) and 0.216 uM(-1) s(-1) and 0.094 uM(-1) s(-1)
      for for cis- and trans-dienelactone, respectively. The kcat/Km ratios for cis
      dienelactone show that both enzymes catalyse the reaction with same efficiency
      even though Km value differs significantly. This is the first report to
      characterize and compare reaction kinetics of purified TfdEI and TfdEII from
      Cupriavidus necator JMP134 and may be helpful for further exploration of their
      catalytic mechanisms.

PMID- 25054966
TI  - Nebivolol reduces central blood pressure in stage I hypertensive patients:
      experimental single cohort study.
AB  - CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP) has grown
      substantially over recent years because evidence has shown that central BP is
      more relevant to cardiovascular outcomes than peripheral BP. Thus, different
      classes of antihypertensive drugs have different effects on central BP despite
      similar reductions in brachial BP. The aim of this study was to investigate the
      effect of nebivolol, a beta-blocker with vasodilator properties, on the
      biochemical and hemodynamic parameters of hypertensive patients. DESIGN AND
      SETTING: Experimental single cohort study conducted in the outpatient clinic of a
      university hospital. METHODS: Twenty-six patients were recruited. All of them
      underwent biochemical and hemodynamic evaluation (BP, heart rate (HR), central BP
      and augmentation index) before and after 3 months of using nebivolol. RESULTS:
      88.5% of the patients were male; their mean age was 49.7 +/- 9.3 years and most
      of them were overweight (29.6 +/- 3.1 kg/m2) with large abdominal waist (102.1 +/
      7.2 cm). There were significant decreases in peripheral systolic BP (P =
      0.0020), diastolic BP (P = 0.0049), HR (P < 0.0001) and central BP (129.9 +/-
      12.3 versus 122.3 +/- 10.3 mmHg; P = 0.0083) after treatment, in comparison with
      the baseline values. There was no statistical difference in the augmentation
      index or in the biochemical parameters, from before to after the treatment.
      CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of
      central BP in stage I hypertensive patients, in addition to reductions in
      brachial systolic and diastolic BP.

PMID- 25054967
TI  - Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema
      attacks: prospective experimental single-cohort study.
AB  - CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE) with C1 inhibitor deficiency
      manifests as recurrent episodes of edema involving the skin, upper respiratory
      tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here
      was to evaluate the response to therapy for these attacks using icatibant, an
      inhibitor of the bradykinin receptor, which was recently introduced into Brazil.
      DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy
      and safety of icatibant for HAE patients. METHODS: Patients with a confirmed HAE
      diagnosis were enrolled according to symptoms and regardless of the time since
      onset of the attack. Icatibant was administered in accordance with the protocol
      that has been approved in Brazil. Symptom severity was assessed continuously and
      adverse events were monitored. RESULTS: 24 attacks in 20 HAE patients were
      treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms
      were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway
      obstruction (10/24). The time taken until onset of relief was: 5-10 minutes
      (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and
      2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged
      from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites.
      Mild to moderate erythema and/or feelings of burning were reported by 15/24
      patients, itching by 3 and no adverse effects in 6. CONCLUSION: HAE type I
      patients who received icatibant responded promptly; most achieved improved
      symptom severity within 30 minutes. Local adverse events occurred in 75% of the
      patients.

PMID- 25054968
TI  - Relationship between birth weight and overweight/obesity among students in
      Florianopolis, Santa Catarina, Brazil: a retrospective cohort study.
AB  - CONTEXT AND OBJECTIVE: Being born heavier than 4 kg is associated with current
      overweight and obesity over the long term. The objective here was to ascertain
      whether birth weight was related to overweight or obese status, among 7 to 14
      year-old schoolchildren, taking into consideration the possible interactions
      between socioeconomic factors and other biological variables. DESIGN AND SETTING:
      Retrospective cohort study on a probabilistic sample of 2,696 children and
      adolescents living in Florianopolis, Santa Catarina, Brazil. METHODS: The
      following data were collected: anthropometric (student's weight, height and age;
      and parents' weight and height), socioeconomic (family income, number of people
      in house and parental schooling level), birth weight and gestational age.
      Overweight and obesity were classified using percentiles of body mass index and
      triceps and subscapular skinfolds. The outcome variables were overweight and
      obesity and the main explanatory variables were birth weight and birth weight
      according to gestational age. The control variables were the parents' nutritional
      status, their schooling level and the per capita family income. Poisson
      multivariate regressions were carried out. RESULTS: Higher prevalence of high
      birth weight was observed among overweight male adolescents (PR = 1.14; 95% CI =
      1.02-1.27; P = 0.03), but this was not observed among obese male adolescents. Low
      birth weight and being born small for gestational age were also not associated
      with the outcomes. Among overweight and obese children, birth weight was not
      significantly different from that of normal-weight children. CONCLUSION: No
      significant association between birth weight and obesity was observed. However,
      there was a weak but significant association between high birth weight and
      overweight, among male adolescents.

PMID- 25054969
TI  - Audiometric thresholds and auditory processing in children with early
      malnutrition: a retrospective cohort study.
AB  - CONTEXT AND OBJECTIVE: Malnutrition is one of the causes of changes in cell
      metabolism. The inner ear has few energy reserves and high metabolism. The aim of
      this study was to analyze whether malnutrition at an early age is related to
      impairment of auditory processing abilities and hearing abnormalities. DESIGN AND
      SETTING: Retrospective cohort study conducted in a tertiary public hospital.
      METHODS: 45 children participated, divided as follows: G1, children diagnosed
      with malnutrition in their first two years of life; G2, children without history
      of malnutrition but with learning difficulties; G3, children without history of
      malnutrition and without learning difficulties. Tympanometry, pure-tone
      audiometry and the Staggered Spondaic Word (SSW) test (auditory processing) were
      performed. Statistical inferences were made using the Kruskal-Wallis test (alpha
      = 5%) and the test of equality of proportions between two samples (alpha = 1.7%).
      RESULTS: None of the 45 children participating in this study presented hearing
      deficiencies. However, at six of the eight frequencies analyzed, the children in
      G1 presented hearing thresholds lower than those of the other groups. In the
      auditory processing evaluation test, it was observed that 100% of the children in
      G1 presented abnormal auditory processing and that G1 and G2 had similar
      proportions of abnormalities (P-values: G1/G2 = 0.1; G1/G3 > 0.001; G2/G3 =
      0.008). CONCLUSIONS: Malnutrition at an early age caused lowering of the hearing
      levels, although this impairment could not be considered to be a hearing
      deficiency. Every child in this group presented abnormalities in auditory
      processing abilities.

PMID- 25054970
TI  - Role of dystrophin in airway smooth muscle phenotype, contraction and lung
      function.
AB  - Dystrophin links the transmembrane dystrophin-glycoprotein complex to the actin
      cytoskeleton. We have shown that dystrophin-glycoprotein complex subunits are
      markers for airway smooth muscle phenotype maturation and together with caveolin
      1, play an important role in calcium homeostasis. We tested if dystrophin affects
      phenotype maturation, tracheal contraction and lung physiology. We used
      dystrophin deficient Golden Retriever dogs (GRMD) and mdx mice vs healthy control
      animals in our approach. We found significant reduction of contractile protein
      markers: smooth muscle myosin heavy chain (smMHC) and calponin and reduced Ca2+
      response to contractile agonist in dystrophin deficient cells.
      Immunocytochemistry revealed reduced stress fibers and number of smMHC positive
      cells in dystrophin-deficient cells, when compared to control. Immunoblot
      analysis of Akt1, GSK3beta and mTOR phosphorylation further revealed that
      downstream PI3K signaling, which is essential for phenotype maturation, was
      suppressed in dystrophin deficient cell cultures. Tracheal rings from mdx mice
      showed significant reduction in the isometric contraction to methacholine (MCh)
      when compared to genetic control BL10ScSnJ mice (wild-type). In vivo lung
      function studies using a small animal ventilator revealed a significant reduction
      in peak airway resistance induced by maximum concentrations of inhaled MCh in mdx
      mice, while there was no change in other lung function parameters. These data
      show that the lack of dystrophin is associated with a concomitant suppression of
      ASM cell phenotype maturation in vitro, ASM contraction ex vivo and lung function
      in vivo, indicating that a linkage between the DGC and the actin cytoskeleton via
      dystrophin is a determinant of the phenotype and functional properties of ASM. 

PMID- 25054972
TI  - Employment among patients with multiple sclerosis-a population study.
AB  - OBJECTIVE: To investigate demographic and clinical factors associated with
      employment in MS. METHODS: The study included 213 (89.9%) of all MS patients in
      Sogn and Fjordane County, Western Norway at December 31st 2010. The patients
      underwent clinical evaluation, structured interviews and completed self-reported
      questionnaires. Demographic and clinical factors were compared between patients
      being employed versus patients being unemployed and according to disease course
      of MS. Logistic regression analysis was used to identify factors independently
      associated with current employment. RESULTS: After a mean disease duration of
      almost 19 years, 45% of the population was currently full-time or part- time
      employed. Patients with relapsing -remitting MS (RRMS) had higher employment rate
      than patients with secondary (SPMS) and primary progressive (PPMS). Higher
      educated MS patients with lower age at onset, shorter disease duration, less
      severe disability and less fatigue were most likely to be employed. CONCLUSIONS:
      Nearly half of all MS patients were still employed after almost two decades of
      having MS. Lower age at onset, shorter disease duration, higher education, less
      fatigue and less disability were independently associated with current
      employment. These key clinical and demographic factors are important to
      understand the reasons to work ability in MS. The findings highlight the need for
      environmental adjustments at the workplace to accommodate individual 's needs in
      order to improve working ability among MS patients.

PMID- 25054973
TI  - Association between serum malondialdehyde levels and mortality in patients with
      severe brain trauma injury.
AB  - There is a hyperoxidative state in patients with trauma brain injury (TBI).
      Malondialdehyde (MDA) is an end-product formed during oxidative stress,
      concretely lipid peroxidation. In small studies (highest sample size 50
      patients), higher levels of MDA have been found in nonsurviving than surviving
      patients with TBI. An association between serum MDA levels and mortality in
      patients with TBI, however, has not been reported. Thus, the objective of this
      prospective, observational, multicenter study, performed in six Spanish intensive
      care units, was to determine whether MDA serum levels are associated with early
      mortality in a large series of patients with severe TBI. Serum MDA levels were
      measured in 100 patients with severe TBI on day 1 and in 75 healthy controls. The
      end-point of the study was 30-day mortality. We found higher serum MDA levels in
      patients with severe TBI than in healthy controls (p < 0.001). Nonsurviving
      patients with TBI (n = 27) showed higher serum MDA levels (p < 0.001) than
      survivors (n = 73). Logistic regression analysis showed that serum MDA levels
      were associated with 30-day mortality (odds ratio [OR] = 4.662; 95% confidence
      interval [CI] = 1.466-14.824; p = 0.01), controlling for Glasgow Coma Score, age,
      and computed tomography findings. Survival analysis showed that patients with
      serum MDA levels higher than 1.96 nmol/mL presented increased 30-day mortality
      than patients with lower levels (hazard ratio = 3.5; 95% CI = 1.43-8.47; p <
      0.001). Thus, the most relevant new finding of our study, the largest to date on
      serum MDA levels in patients with severe TBI, was an association between serum
      MDA levels and early mortality.

PMID- 25054974
TI  - The Global Burden of Disease 2010 update: keeping mental health in the spotlight.

PMID- 25054975
TI  - The global burden of disease studies: tracking the progress of a moving train.

PMID- 25054971
TI  - The influence of Pleistocene climatic changes and ocean currents on the
      phylogeography of the southern African barnacle, Tetraclita serrata (Thoracica;
      Cirripedia).
AB  - The evolutionary effects of glacial periods are poorly understood for Southern
      Hemisphere marine intertidal species, particularly obligatory sessile organisms.
      We examined this by assessing the phylogeographic patterns of the southern
      African volcano barnacle, Tetraclita serrata, a dominant species on rocky
      intertidal shores. Restricted gene flow in some geographical areas was
      hypothesized based on oceanic circulation patterns and known biogeographic
      regions. Barnacle population genetic structure was investigated using the
      mitochondrial cytochrome oxidase subunit 1 (COI) region for 410 individuals
      sampled from 20 localities spanning the South African coast. The mtDNA data were
      augmented by generating nuclear internal transcribed spacer 1 (ITS1) sequences
      from a subset of samples. Phylogenetic and population genetic analyses of
      mitochondrial DNA data reveal two distinct clades with mostly sympatric
      distributions, whereas nuclear analyses reveal only a single lineage. Shallow,
      but significant structure (0.0041-0.0065, P<0.01) was detected for the mtDNA data
      set, with the south-west African region identified as harbouring the highest
      levels of genetic diversity. Gene flow analyses on the mtDNA data show that
      individuals sampled in south-western localities experience gene flow primarily in
      the direction of the Benguela Current, while south and eastern localities
      experience bi-directional gene flow, suggesting an influence of both the inshore
      currents and the offshore Agulhas Current in the larval distribution of T.
      serrata. The mtDNA haplotype network, Bayesian Skyline Plots, mismatch
      distributions and time since expansion indicate that T. serrata population
      numbers were not severely affected by the Last Glacial Maximum (LGM), unlike
      other southern African marine species. The processes resulting in the two
      morphologically cryptic mtDNA lineages may be the result of a recent historical
      allopatric event followed by secondary contact or could reflect selective
      pressures due to differing environmental conditions. 

PMID- 25054976
TI  - Electrodeposition of thick palladium coatings from a palladium(II)-containing
      ionic liquid.
AB  - The first palladium-containing Liquid Metal Salts (LMS) are presented and shown
      to be suitable electrolytes for the electrodeposition of palladium. The
      homoleptic LMS of formula [Pd(MeIm)4][Tf2N]2 or [Pd(EtIm)4][Tf2N]2 (MeIm = N
      methylimidazole, EtIm = N-ethylimidazole) have higher melting points than the
      heteroleptic [Pd(MeIm)2(EtIm)2][Tf2N]2, which is proved to be the most promising
      electrolyte. The deposition reaction in these LMS was found to be irreversible
      but smooth and dense palladium layers can be deposited that are crack-free up to
      a thickness of 10 microns. 

PMID- 25054977
TI  - Potential impact of point-of-care INR testing on intravenous thrombolysis.

PMID- 25054978
TI  - Is point-of-care accurate for indicating thrombolysis in anticoagulated patients
      on oral anticoagulation treatments?
AB  - The use of oral anticoagulation treatment (OAT) in patients with an international
      normalized ratio (INR) higher than 1.7 is a contraindication to thrombolysis in
      acute ischemic stroke. The aim of the present study is to compare the use of
      point-of-care (POC) coagulometers to the standard coagulation analysis (SCA)
      procedure of the INR as a decision-making test for use with patients taking OAT.
      METHOD: Eighty patients on chronic OAT underwent a POC and an SCA during a
      regular outpatient evaluation. RESULTS: When comparing the abilities of the POC
      test and the SCA test to identify adequate levels for thrombolysis (<=1.7), the
      POC had a sensitivity of 96.6% (95%CI 88.4-99.1) and a specificity of 60.0%
      (95%CI 38.6-78). POC overestimated INR levels by 0.51 points compared to the SCA
      test. CONCLUSION: POC has a high sensitivity compared to the SCA test for the
      identification of patients within the cut-off point for thrombolysis.

PMID- 25054979
TI  - Coping strategies and mood profiles in patients with multiple sclerosis.
AB  - OBJECTIVE: The aim of the present study was to investigate the coping strategies,
      mood characteristics and the association between these aspects in patients
      diagnosed with multiple sclerosis and healthy subjects. METHOD: Fifty consecutive
      patients who were diagnosed with multiple sclerosis according to McDonald
      criteria and thirty-one healthy subjects were included in the study. In addition
      to the sociodemographic form, Expanded Disability Status Scale (EDSS), Coping
      Orientation for Problem Experiences Scale (COPE), and Profile of Mood States
      (POMS) tests were applied to the participants. RESULTS: Non-functional coping
      strategies were significantly higher in the secondary-progressive type (p<=0.05).
      Depression-dejection, fatigue-inertia and total POMS scores were significantly
      higher in the secondary-progressive type (p<=0.05). CONCLUSION: The results of
      our study demonstrate the importance of rehabilitation programs that encourage
      exercise among patients with multiple sclerosis to increase vigor-activity
      levels.

PMID- 25054980
TI  - Neurological complications after H1N1 influenza vaccination: magnetic resonance
      imaging findings.
AB  - OBJECTIVE: To report 4 different neurological complications of H1N1 virus
      vaccination. METHOD: Four patients (9, 16, 37 and 69 years of age) had
      neurological symptoms (intracranial hypertension, ataxia, left peripheral facial
      palsy of abrupt onset, altered mental status, myelitis) starting 4-15 days after
      H1N1 vaccination. MRI was obtained during the acute period. RESULTS: One patient
      with high T2 signal in the cerebellum interpreted as acute cerebellitis; another,
      with left facial palsy, showed contrast enhancement within both internal auditory
      canals was present, however it was more important in the right side; one patient
      showed gyriform hyperintensities on FLAIR with sulcal effacement in the right
      fronto-parietal region; and the last one showed findings compatible with thoracic
      myelitis. CONCLUSION: H1N1 vaccination can result in important neurological
      complications probably secondary to post-vaccination inflammation. MRI detected
      abnormalities in all patients.

PMID- 25054982
TI  - Cerebrospinal fluid can be used for HIV genotyping when it fails in blood.
AB  - Blood plasma specimens are the clinical standard for HIV-1 pol gene genotyping
      from viral populations; however, it is not always successful, often from low
      viral loads or the presence of polymerase chain reaction (PCR) inhibitors.
      Objective To describe the successful of HIV-1 genotyping in two samples of
      cerebrospinal fluid (CSF), after genotype procedures failed from blood. Method
      Two HIV-infected patients enrolled in a neurocognitive research study were
      evaluated when standard HIV-1 genotyping failed from blood plasma samples.
      Genotyping was performed using the commercial system TRUGENE HIV-1 Genotyping Kit
      and the OpenGene DNA Sequencing System (Siemens Healthcare Diagnostics,
      Tarrytown, NY, USA). Results CSF genotyping was performed via the same commercial
      platform and was successful in both cases. Conclusion This report demonstrates
      that CSF could be used as an alternate clinical specimen for HIV-1 genotyping
      when it fails from blood.

PMID- 25054983
TI  - Small calcified lesions suggestive of neurocysticercosis are associated with
      mesial temporal sclerosis.
AB  - Recent studies have suggested a possible relationship between temporal lobe
      epilepsy with mesial temporal sclerosis (MTS) and neurocysticercosis (NC). We
      performed a case-control study to evaluate the association of NC and MTS. METHOD:
      We randomly selected patients with different epilepsy types, including: MTS,
      primary generalized epilepsy (PGE) and focal symptomatic epilepsy (FSE). Patients
      underwent a structured interview, followed by head computed tomography (CT). A
      neuroradiologist evaluated the scan for presence of calcified lesions suggestive
      of NC. CT results were matched with patients' data. RESULTS: More patients in the
      MTS group displayed calcified lesions suggestive of NC than patients in the other
      groups (p=0.002). On multivariate analysis, MTS was found to be an independent
      predictor of one or more calcified NC lesions (p=0.033). CONCLUSION: After
      controlling for confounding factors, we found an independent association between
      NC calcified lesions and MTS.

PMID- 25054981
TI  - Portable lactate analyzer for measuring lactate in cerebrospinal fluid (CSF) and
      plasma - method-comparison evaluations.
AB  - Increased plasma lactate levels can indicate the presence of metabolic disorders
      in HIV infected individuals. OBJECTIVE: To determine whether a portable analyzer
      is valid for measuring cerebrospinal fluid (CSF) and plasma lactate levels in HIV
      infected individuals. METHOD: CSF and plasma were collected from 178 subjects.
      Samples tested by the Accutrend portable analyzer were compared to those tested
      by a reference device (SYNCHRON LX 20). RESULTS: The portable analyzer had in
      plasma sensitivity of 0.95 and specificity 0.87. For CSF the specificity was
      0.95; the sensitivity 0.33; the negative predictive value was 95% and the
      positive predictive value 33%. CONCLUSIONS: These findings support the validity
      of the portable analyzer in measuring lactate concentrations in CSF that fall
      within the normal range. The relatively poor positive predictive value indicates
      that a result above the reference range may represent a "false positive test",
      and should be confirmed by the reference device before concluding abnormality.

PMID- 25054984
TI  - Neurodevelopment of small-for-gestational age infants: behavioral aspects in
      first year.
AB  - The purpose of this study was to compare the behavior of full-term small-for
      gestational age (SGA) with full-term appropriate-for gestational age (AGA)
      infants in the first year of life. We prospectively evaluated 68 infants in the
      2nd month, 67 in the 6th month and 69 in the 12th month. The Bayley Scales of
      Infant Development-II were used, with emphasis on the Behavior Rating Scale
      (BRS). The groups were similar concerning the item "interest in test materials
      and stimuli"; there was a trend toward differences in the items "negative
      affect", "hypersensitivity to test materials" and "adaptation to change in test
      materials". The mean of Raw Score was significantly lower for the SGA group in
      the items "predominant state", "liability of state of arousal", "positive
      affect", "soothability when upset", "energy", "exploration of objects and
      surroundings", "orientation toward examiner". A lower BRS score was associated
      with the SGA group in the 2nd month. 

PMID- 25054985
TI  - Endoscopic third ventriculostomy has no higher costs than ventriculoperitoneal
      shunt.
AB  - OBJECTIVE: To evaluate the cost of endoscopic third ventriculostomy (ETV)
      compared to ventriculoperitoneal shunt (VPS) in the treatment of hydrocephalus in
      children. METHOD: We studied 103 children with hydrocephalus, 52 of which were
      treated with ETV and 51 with VPS in a prospective cohort. Treatment costs were
      compared within the first year after surgery, including subsequent surgery or
      hospitalization. RESULTS: Twenty (38.4%) of the 52 children treated with VPS
      needed another procedure due to shunt failure, compared to 11 (21.5%) of 51
      children in the ETV group. The average costs per patient in the group treated
      with ETV was USD$ 2,177,66+/-517.73 compared to USD$ 2,890.68+/-2,835.02 for the
      VPS group. CONCLUSIONS: In this series there was no significant difference in
      costs between the ETV and VPS groups.

PMID- 25054986
TI  - Foramen magnum meningiomas: surgical treatment in a single public institution in
      a developing country.
AB  - OBJECTIVE: To analyze the clinical outcome of patients with foramen magnum (FM)
      meningiomas. METHOD: Thirteen patients (11 Feminine / 2 Masculine with FM
      meningiomas operated on through lateral suboccipital approach were studied.
      Clinical outcome were analyzed using survival (SC) and recurrence-free survival
      curves (RFSC). RESULTS: All tumors were World Health Organization grade I. Total,
      subtotal and partial resections were acchieved in 69.2%, 23.1% and 7.7%,
      respectively, and SC was better for males and RFSC for females. Tumor location,
      extent of resection and involvement of vertebral artery/lower cranial nerves did
      not influence SC and RFSC. Recurrence rate was 7.7%. Operative mortality was 0.
      Main complications were transient (38.5%) and permanent (7.7%) lower cranial
      nerve deficits, cerebrospinal fluid fistula (30.8%), and transient and permanent
      respiratory difficulties in 7.7% each. CONCLUSIONS: FM meningiomas can be
      adequately treated in public hospitals in developing countries if a
      multidisciplinary team is available for managing postoperative lower cranial
      nerve deficits.

PMID- 25054987
TI  - From exercise intolerance to functional improvement: the second wind phenomenon
      in the identification of McArdle disease.
AB  - McArdle disease is the most common of the glycogen storage diseases. Onset of
      symptoms is usually in childhood with muscle pain and restricted exercise
      capacity. Signs and symptoms are often ignored in children or put down to
      'growing pains' and thus diagnosis is often delayed. Misdiagnosis is not uncommon
      because several other conditions such as muscular dystrophy and muscle
      channelopathies can manifest with similar symptoms. A simple exercise test
      performed in the clinic can however help to identify patients by revealing the
      second wind phenomenon which is pathognomonic of the condition. Here a patient is
      reported illustrating the value of using a simple 12 minute walk test. 

PMID- 25054988
TI  - Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric
      disorders: a systematic review.
AB  - We reviewed trigeminal nerve stimulation (TNS) and transcutaneous vagus nerve
      stimulation (tVNS). All techniques have shown preliminary promising results,
      although the results are mixed. METHOD: We performed a systematic review of the
      Medline and Embase databases, with no constraint to dates, through June 2013. The
      keywords were [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3)
      trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve
      stimulation] and (6) mental disorders. RESULTS: We included four preclinical and
      clinical five studies on TNS. All clinical data were based on open-label studies
      with small samples, which diminished the external validity of the results, thus
      reflecting the modest impact of TNS in current clinical practice. Of the tVNS
      clinical trials, three assessed physiological features in healthy volunteers, and
      one examined patients with epilepsy. CONCLUSION: TNS and tVNS improve treatment
      of particular neuropsychiatric disorders such as depression.

PMID- 25054989
TI  - Histiocytosis: a review focusing on neuroimaging findings.
AB  - OBJECTIVE: Histiocytosis is a systemic disease that usually affects the central
      nervous system. The aim of this study is to discuss the neuroimaging
      characteristics of Langerhans cell histiocytosis (LCH), the most common of these
      diseases; and the non-Langerhans cells histiocytosis (NLCH), which includes
      entities such as hemophagocytic syndrome, Erdheim-Chester and Rosai-Dorfman
      diseases. METHOD: Literature review and illustrative cases with pathologic
      confirmation. RESULTS: In LCH, the most common findings are 1) osseous lesions in
      the craniofacial bones and/or skull base; 2) intracranial, extra-axial changes;
      3) intra-axial parenchymal changes (white and gray matter); 4) atrophy. Among the
      NLCH, diagnosis usually requires correlation with clinical and laboratory
      criteria. The spectrum of presentation includes intraparenchymal involvement,
      meningeal lesions, orbits and paranasal sinus involvement. CONCLUSION: It is
      important the recognition of the most common imaging patterns, in order to
      include LCH and NLCH in the differential diagnosis, whenever pertinent.

PMID- 25054990
TI  - Evolution of the concept of dystonia.
AB  - The term dystonia was proposed by Hermann Oppenheim in 1911, but reports of
      cervical dystonia are finding since the Roman Empire. The differentiation of the
      dystonia between a neurological and a psychiatric disease turned a lot. Sometimes
      was proposed, further, the exclusion of the dystonia as a different phenomenon
      among the movement disorders. The hypothesis of emotional etiology of the
      dystonias increase in the decade of 1960 and the conclusion of the etiology of
      dystonia only happened in the decades of 1970 and 1980 with a series of works of
      Charles David Marsden. These researches defined dystonia as a movement disorder
      caused by lesion in the basal ganglia. In February of 1984, a committee of
      members of Scientific Advisory Board of the Dystonia Medical Research Foundation
      developed the definition for dystonia accepts until 2013 when an international
      committee developed the new concept. 

PMID- 25054991
TI  - Jean-Baptiste Charcot, the French Antarctic expedition and scurvy.
AB  - During the second expedition to the South Pole, Commander Jean-Baptiste Charcot
      and some members of the crew of "Pourquoi Pas?" developed symptoms suggestive of
      scurvy. The clinical picture was totally reversed after dietary changes. 

PMID- 25054992
TI  - The development of the dementia concept in 19th century.
AB  - The dementia concept has been reformulated through its history and the 19th
      century was remarkable in the construction of this concept as we understand it
      today. Like other syndromes, much of the history of the dementia concept comes
      from the attempt to separate it from other nosological conditions, giving it a
      unique identity. The fundamental elements for the arising of the dementia modern
      concept were: a) correlation of the observed syndrome with organic-cerebral
      lesions; b) understanding of the irreversibility of the dementia evolution; c)
      its relation with human ageing; and d) the choice of the cognitive dysfunction as
      a clinical marker of the dementia concept. 

PMID- 25054993
TI  - How long does it take for putting on sneakers? An obsessive-compulsive ritual.

PMID- 25054994
TI  - Overlapping MRI findings in progressive supranuclear palsy - corticobasal
      syndrome.

PMID- 25054995
TI  - Reversible cerebral vasoconstriction syndrome associated with putaminal
      hemorrhage.

PMID- 25054996
TI  - Bright tongue sign: a diagnostic marker for amyotrophic lateral sclerosis.

PMID- 25054997
TI  - Parkinsonism as a neuropsychiatric presentation in CNS gnathosomiasis: its
      prevalence.

PMID- 25054998
TI  - Poliomyelitis: a new old disease. What is the value of continuing education
      programs for health professionals?

PMID- 25055000
TI  - Insights into the composition and sources of rural, urban and roadside
      carbonaceous PM10.
AB  - Insights into the nature and sources of the urban and roadside increments in
      carbonaceous PM10 are gained from bulk chemical analyses on daily filter samples
      collected at a roadside, urban background and rural site in Edinburgh, UK (not
      all sampling contemporaneous). The concentrations of PM10 water-soluble organic
      matter (WSOM) at the three sites were similar, and (where measured concurrently)
      strongly correlated, indicating a uniform background source, in contrast to the
      black carbon component (quantified by filter optical reflectance) whose average
      concentrations at urban background and roadside were, respectively, about 3 and 7
      times greater than at the rural site, indicating local urban sources. BC was not
      a major component of PM10 but was a major component of the urban and roadside
      PM10 increments (~50% and ~60% respectively). The roadside WSOM had greater
      hydrophobicity than the urban background WSOM. UV-vis spectra indicated increased
      prevalence of unsaturated bonds and conjugation in urban background WSOM in
      winter compared with summer. This is consistent with both summertime
      photochemical production of particle OM and maritime primary aliphatic WSOM.
      Raman microscopy of a small subset of samples indicated carbon functionality
      ranged between diesel-like material and more complex humic-like material. Results
      overall indicate the presence of a background functionalized carbonaceous
      material, with local BC sources superimposed. 

PMID- 25055001
TI  - Repeated High-Intensity-Effort Activity in Elite and Semielite Rugby League Match
      Play.
AB  - PURPOSE: No study has investigated the frequency and nature of repeated high
      intensity-effort (RHIE) bouts across elite and semielite rugby league
      competitions. This study examined RHIE activity in rugby league match play across
      playing standards. PARTICIPANTS: 36 elite and 64 semielite rugby league players.
      METHODS: Global positioning system analysis was completed during 17 elite and 14
      semielite matches. RESULTS: The most commonly occurring RHIE bouts involved 2
      efforts (2-RHIE) for both elite and semielite players. Only small differences
      were found in 2-RHIE activity between elite and semielite match play (effect size
      [ES] >= 0.31 +/- 0.15, >= 88%, likely). RHIE bouts were more likely to involve
      contact as the number of efforts in a bout increased (ES >=0.40 +/- 0.15, 100%,
      almost certainly). Semielite players performed a greater proportion of 2-contact
      effort RHIE bouts than their elite counterparts (68.2% vs 60.6%, ES 0.33 +/-
      0.15, 92%, likely), while elite players performed a greater proportion of 3
      effort bouts (26.9% vs 21.1%, ES 0.31 +/- 0.15, 88%, likely). Elite players also
      had a shorter recovery (1.00-3.99 vs >=4.00 min) between RHIE bouts (ES >= 1.60
      +/- 0.71, >= 94%, likely). CONCLUSION: These findings highlight the RHIE demands
      of elite and semielite rugby league match play. Elite players are more likely to
      perform RHIE bouts consisting of 3 efforts and to have a shorter recovery time
      between bouts. Exposing players to these RHIE demands in training is likely to
      improve their ability to tolerate the most demanding passages of match play.

PMID- 25055002
TI  - Molecular volumes of DOPC and DOPS in mixed bilayers of multilamellar vesicles.
AB  - The mixtures of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl
      sn-glycero-3-phospho-l-serine (DOPS) in bilayers of multilamellar vesicles were
      studied by method of densitometry. In the range of DOPS molar fraction 0-100%,
      specific volumes of mixtures of lipids coincide with theoretical values in the
      case of ideal mixing of lipids. The coefficient of thermal volume expansivity was
      evaluated for different DOPS molar fractions; it has values in the range (71.1
      73.6) * 10(-5) K(-1). Molecular volumes for pure DOPC and DOPS were evaluated for
      temperature range 15-45  degrees C. At 30  degrees C, molecular volumes are 1304
      A(3) and 1254 A(3) for DOPC and DOPS, respectively. The estimated volume of head
      group of DOPS at 30  degrees C is 275 A(3). Time-dependent density scans revealed
      that the dispersion of DOPC vesicle sedimentation during measurements induces an
      observed increasing density of dispersion in agreement with recently published
      observations. The presence of charged DOPS in vesicles prevents them from
      sedimentation and values of density are stable over a prolonged time. 

PMID- 25055003
TI  - Suspected adrenal insufficiency in critically ill burned patients: etomidate
      induced or critical illness-related corticosteroid insufficiency?-A review of the
      literature.
AB  - Adrenal insufficiency (AI), whether etomidate-induced or secondary to critical
      illness-related corticosteroid insufficiency (CIRCI), is a common and under
      appreciated problem in the intensive care unit intensive care unit (ICU).
      However, AI is often difficult to identify and diagnose in the critically ill.
      The pathophysiology and ideal management of etomidate-induced AI and CIRCI,
      especially in burn patients, is unknown. Many studies, however, have examined the
      prevalence of and risk factors for developing AI in critically ill populations as
      well as the effect of AI on morbidity and mortality. Observing a seemingly
      increased number of patients with suspected AI in our burn ICU, we sought to
      evaluate and summarize the current literature relating to adrenal insufficiency
      in the critically ill. We performed an electronic literature search on the PubMed
      and Ovid Medline databases using the key words "etomidate," "adrenal
      insufficiency," "CIRCI," and "burn injury." Relevant studies from the current
      burn and ICU era were selected to be included in this review of the literature.
      Among the critically ill, burn patients are at increased risk for developing
      adrenal insufficiency and the risk is greatest for elderly patients with large
      burns and inhalation injury. Both CIRCI and etomidate-induced AI are associated
      with high morbidity and mortality, therefore avoiding preventable causes of AI,
      such as choosing alternatives to etomidate for rapid sequence intubation (RSI) in
      the severely burn injured patient should be encouraged. Further research is
      indicated to investigate the biological relationship between AI and associated
      morbidity and mortality, whether etomidate-induced or secondary to critical
      illness; as well as how best to identify and diagnose patients with suspected
      adrenal insufficiency in the burn intensive care unit. 

PMID- 25055004
TI  - Outcomes of outpatient management of pediatric burns.
AB  - The literature surrounding pediatric burns has focused on inpatient management.
      The goal of this study is to characterize the population of burned children
      treated as outpatients and assess outcomes validating this method of burn care. A
      retrospective review of 953 patients treated the burn clinic and burn unit of a
      tertiary care center. Patient age, burn etiology, burn characteristics, burn
      mechanism, and referral pattern were recorded. The type of wound care and
      incidence of outcomes including subsequent hospital admission, infection,
      scarring, and surgery served as the primary outcome data. Eight hundred and
      thirty children were treated as outpatients with a mean time of 1.8 days for the
      evaluation of burn injury in our clinic. Scalds accounted for 53% of the burn
      mechanism, with burns to the hand/wrist being the most frequent area involved.
      The mean percentage of TBSA was 1.4% for the outpatient cohort and 8% for the
      inpatient cohort. Burns in the outpatient cohort healed with a mean time of 13.4
      days. In the outpatient cohort, nine (1%) patients had subsequent admissions and
      three (0.4%) patients had concern for infection. Eight patients from the
      outpatient cohort were treated with excision and grafting. The vast majority of
      pediatric burns are small, although they may often involve more critical areas
      such as the face and hand. Outpatient wound care is an effective treatment
      strategy which results in low rates of complications and should become the
      standard of care for children with appropriate burn size and home support. 

PMID- 25055005
TI  - Peripherally inserted central line catheter infections in burn patients.
AB  - Peripherally inserted central line catheter (PICC) use has increased in burn
      patients. While the risks of central line associated blood stream infections
      (CLABSI) in burn patients have been well studied, the risks of PICC infections
      have yet to be fully elucidated. A retrospective chart review was performed of
      all burn patients with a PICC admitted to our regional burn center from 2006 to
      2008. Information collected included: age, total body surface area (TBSA) burn
      injury, length of hospital stay, duration of PICC line insertion, hospital day of
      PICC line insertion, and development of infections. All mean values are presented
      as the mean +/- standard error. A total of 56 patients received a PICC during
      this time period. Eight patients developed PICC infections with an overall rate
      of 11.7/1000 catheter days. Burn patient CLABSI for the same time period was
      12.9/1000 catheter days. Duration of PICC did not differ between infected and
      noninfected patients (13.3 +/- 6 vs. 12.1 +/- 9.6 days). Patients with PICC
      infections had a higher percentage of TBSA (42.7 +/- 3.2 vs. 20.6 +/- 2.4*),
      longer length of admission (72.4 +/- 6 vs. 35 +/- 3.2*), and later hospital day
      of PICC insertion (48 +/- 4.6 vs. 17.1 +/- 2.5*). On linear regression analysis,
      PICC infection was significantly associated with TBSA (B = 22.1*), length of
      admission (B = 37.4*), and hospital day of PICC insertion (B = 30.3*). On
      multivariate analysis, TBSA (Odds ratio [OR] = 1.05*), length of admission (OR =
      1.04*), and hospital day of PICC insertion (OR = 1.05*) all independently
      increased the risk of developing a PICC infection. Patients with severe burn
      injury, long hospital admissions, and later hospital day of PICC insertions are
      at higher risk of developing PICC infections. This data suggests that protocols
      should be developed about routine PICC changes in this high-risk burn population.

PMID- 25055006
TI  - Are visceral proteins valid markers for nutritional status in the burn intensive
      care unit?
AB  - The aim of this study was to determine whether visceral protein levels increase
      under positive nitrogen balance during times of decrease in acute-phase reactant
      levels in patients with burn injury. This was a post hoc analysis of a
      prospective, interventional study approved by the local institutional review
      board. A total of 10 subjects between the ages of 18 and 72 with >= 20% total
      body surface area burn were enrolled over a 14-month period. Data were collected
      for five subjects (average age of 28 +/- 8 years and total body surface area burn
      of 69 +/- 15%) who met the inclusion criteria. Changes in visceral protein levels
      were examined along with nitrogen balance and acute-phase reactants when the
      subjects were on enteral nutrition, and the proteins were not examined during
      times of acute kidney injury. Descriptive statistics were performed, and linear
      regression was used to analyze the association of visceral proteins and nitrogen
      balance during times that acute-phase reactant levels were decreasing. The
      subjects received an average of 3044 +/- 1613 kcal/day (39 +/- 20 kcal/kg),
      meeting 72% of caloric goals and achieving positive nitrogen balance during 68%
      of the 40 weekly measurements, with 174 +/- 85 g of protein intake per day (2.2
      +/- 1.1 g/kg). There was a weak relationship between nitrogen balance and changes
      in visceral protein levels during times that the acute-phase reactant levels were
      decreasing (P > .05). Visceral proteins were found to be poor markers of
      nutritional status. This study is unique because the subjects were able to
      achieve positive nitrogen balance despite severe burns.

PMID- 25055007
TI  - Line of duty firefighter fatalities: an evolving trend over time.
AB  - Between 1990 and 2012, 2775 firefighters were killed in the line of duty.
      Myocardial infarction (MI) was responsible for approximately 40% of these
      mortalities, followed by mechanical trauma, asphyxiation, and burns. Protective
      gear, safety awareness, medical care, and the age of the workforce have evolved
      since 1990, possibly affecting the nature of mortality during this 22-year time
      period. The purpose of this study is to determine whether the causes of
      firefighter mortality have changed over time to allow a targeted focus in
      prevention efforts. The U.S. Fire Administration fatality database was queried
      for all-cause on-duty mortality between 1990 to 2000 and 2002 to 2012. The year
      2001 was excluded due to inability to eliminate the 347 deaths that occurred on
      September 11. Data collected included age range at the time of fatality (exact
      age not included in report), type of duty (on-scene fire, responding, training,
      and returning), incident type (structure fire, motor vehicle crash, etc), and
      nature of fatality (MI, trauma, asphyxiation, cerebrovascular accident [CVA], and
      burns). Data were compared between the two time periods with a chi test. Between
      1990 and 2000, 1140 firefighters sustained a fatal injury while on duty, and 1174
      were killed during 2002 to 2012. MI has increased from 43% to 46.5% of deaths (P
      = .012) between the 2 decades. CVA has increased from 1.6% to 3.7% of deaths (P =
      .002). Asphyxiation has decreased from 12.1% to 7.9% (P = .003) and burns have
      decreased from 7.7% to 3.9% (P = .0004). Electrocution is down from 1.8% to 0.5%
      (P = .004). Death from trauma was unchanged (27.8 to 29.6%, P = .12). The
      percentage of fatalities of firefighters over age 40 years has increased from 52%
      to 65% (P = .0001). Fatality by sex was constant at 3% female. Fatalities during
      training have increased from 7.3% to 11.2% of deaths (P = .00001). The nature of
      firefighter mortality has evolved over time. In the current decade, line-of-duty
      mortality is more likely to occur during training. Mortality from burns,
      asphyxiation, and electrocution has decreased; but death from MI and CVA has
      increased, particularly in older firefighters. Outreach and education should be
      targeted toward vehicle safety, welfare during training, and cardiovascular
      disease prevention in the firefighter population.

PMID- 25055008
TI  - Targeting burn prevention in Ukraine: evaluation of base knowledge in burn
      prevention and first aid treatment.
AB  - Burn prevention has been identified by the World Health Organization (WHO) as a
      topic in need of further investigation and education throughout the world, with
      an increased need in low-income countries. It has been noted that implementing
      educational programs for prevention in high income countries has aided in
      lowering the rate of burn injuries. The purpose of this study is to evaluate the
      current education level of knowledge of prevention and first aid treatment of
      scald burns. A prevention campaign will target these educational needs as a part
      of an outreach program to improve burn care in Ukraine. The research team
      evaluated the current health structure in Ukraine and how it could benefit from
      the increased knowledge of burn prevention and first aid. A test was designed to
      assess the baseline level of knowledge with regard to first aid and scald
      prevention in parents, pregnant woman, and healthcare and daycare providers. A
      total of 14,456 tests were sent to pediatric clinics, obstetrician clinics, and
      daycare facilities to test respondents. A total of 6,120 completed tests were
      returned. Doctors presented with the highest level of knowledge averaging 77.0%
      on prevention and 67.5% on first aid while daycare workers presented the largest
      gap in knowledge at 65.0% in prevention and 54.3% in first aid. Interest in
      further educational materials was reported by 92% of respondents. The results of
      this study clearly show a lack of knowledge in first aid and prevention of scald
      burn injury in all the populations tested.

PMID- 25055009
TI  - Modifications to the Aesop's Fable paradigm change New Caledonian crow
      performances.
AB  - While humans are able to understand much about causality, it is unclear to what
      extent non-human animals can do the same. The Aesop's Fable paradigm requires an
      animal to drop stones into a water-filled tube to bring a floating food reward
      within reach. Rook, Eurasian jay, and New Caledonian crow performances are
      similar to those of children under seven years of age when solving this task.
      However, we know very little about the cognition underpinning these birds'
      performances. Here, we address several limitations of previous Aesop's Fable
      studies to gain insight into the causal cognition of New Caledonian crows. Our
      results provide the first evidence that any non-human animal can solve the U-tube
      task and can discriminate between water-filled tubes of different volumes.
      However, our results do not provide support for the hypothesis that these crows
      can infer the presence of a hidden causal mechanism. They also call into question
      previous object-discrimination performances. The methodologies outlined here
      should allow for more powerful comparisons between humans and other animal
      species and thus help us to determine which aspects of causal cognition are
      distinct to humans.

PMID- 25055010
TI  - WHO Western Pacific Regional Action Plan for the Prevention and Control of NCDs
      (2014-2020).
AB  - This is an excerpt of the "Western Pacific Regional Action Plan for the
      Prevention and Control of Noncommunicable Diseases (2014-2020)" (RAP NCD) which
      has been endorsed by the Member States of the Western Pacific Region of World
      Health Organization (WHO) in October 2013. The Regional plan is fully harmonized
      with the Global Action Plan for the Prevention and Control of Noncommunicable
      Diseases (2013-2020). The regional plan calls for a systematic approach to NCD
      prevention and control. The plan provides a road map and a menu of very cost
      effective interventions for all Member States and other stakeholders, to take
      coordinated and coherent action at all levels to attain the nine voluntary global
      target by 2025. The original version of RAP NCD is downloadable from the website
      (http://www.wpro.who.int/noncommunicable_diseases/ WHO_NCD_RAP.pdf?ua=1). In
      addition, there are NCD tools in the WHO homepage (http://www.who.int/nmh/ncd
      tools/en/). 

PMID- 25055011
TI  - mTOR: a new therapeutic target for pediatric low-grade glioma?

PMID- 25055012
TI  - Prioritizing uncharacterized genes in the search for glioma biomarkers.

PMID- 25055013
TI  - Tumor blood volume: a prognostic biomarker for anaplastic astrocytomas?

PMID- 25055016
TI  - A selected review of abstracts from the 4th Quadrennial Meeting of the World
      Federation of Neuro-Oncology.
AB  - The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology (WFNO), San
      Francisco, CA, USA, 21-24 November 2013 The 4th Quadrennial Meeting of the World
      Federation of Neuro-Oncology (WFNO) was the largest neuro-oncology meeting that
      meets once every 4 years and brings together clinicians and scientists from all
      parts of the world whose focus is on new brain cancer clinical trials and
      research primarily pertaining to gliomas. The WFNO 2013 meeting included 1
      education day, 2.5 days of presentation, 13 sunrise sessions, one town hall
      meeting, one mini-symposium, 130 oral presentations and 900 abstracts. This short
      meeting review highlights select adult clinical abstracts presented at WFNO 2013
      that will only in part encompass the contents of a large and multifaceted
      meeting. 

PMID- 25055017
TI  - Nanocarrier-based therapies for CNS tumors.
AB  - Current chemotherapeutic strategies for tumors of the CNS are largely
      ineffective. This is due, in part, to the lack of robust drug delivery systems.
      The blood-brain barrier hinders the passage of systemically delivered
      therapeutics, and the brain extracellular matrix limits the distribution and
      longevity of locally delivered agents. Drug-loaded nanocarriers represent a
      promising strategy to overcome these barriers. Due to their small size and
      versatile design, nanocarriers can be finely tuned to address specific drug
      delivery challenges. Here, we review the major advances in development of
      nanocarrier-based therapeutics for tumors of the CNS, with an emphasis on
      polymeric nanoparticles.

PMID- 25055018
TI  - Molecular and genetic pathways in gliomas: the future of personalized
      therapeutics.
AB  - In the last few decades, we have seen significant advances in brain imaging,
      which have resulted in more detailed anatomic and functional localization of
      gliomas in relation to the eloquent cortex, as well as improvements in
      microsurgical techniques and enhanced delivery of adjuvant stereotactic
      radiation. While these advancements have led to a relatively modest improvement
      in clinical outcomes for patients with malignant gliomas, much more work remains
      to be done. As with other types of cancer, we are now rapidly moving past the era
      of histopathology dictating treatment for brain tumors and into the realm of
      molecular diagnostics and associated targeted therapies, specifically based on
      the genomic architecture of individual gliomas. In this review, we discuss the
      current era of molecular glioma characterization and how these profiles will
      allow for individualized, patient-specific targeted treatments.

PMID- 25055019
TI  - Update on management of vertebral column tumors.
AB  - Treatment options for metastatic and primary spinal tumors have expanded in
      recent years, in part due to the advances made in stereotactic radiosurgery. For
      metastatic spinal tumors, our institution utilizes the neurologic, oncologic,
      mechanical, and systemic (NOMS) decision framework, which provides a treatment
      paradigm based on the neurologic, oncologic, mechanical and systemic status of
      the patient. Radiosurgery as a supplement to surgical decompression has allowed
      for less-invasive surgical procedures carrying minimal morbidity while still
      providing effective local tumor control. Although wide en bloc excision has
      traditionally been the goal for the treatment of high-grade primary spine tumors,
      recent studies have shown promise for radiosurgery in providing control in tumors
      such as chordomas and high-grade sarcomas. Despite advances in radiosurgery,
      there continues to be limitations in providing effective conformational doses
      with minimal toxicity to critical structures. One of the ways to circumvent this
      and supplement external beam radiation is through the use of brachytherapy
      delivered by radioactive plaque or seeds.

PMID- 25055020
TI  - Proton therapy for the treatment of children with CNS malignancies.
AB  - Proton therapy is a novel technique for treating pediatric malignancies. As a
      tool to reduce normal-tissue dose, it has the potential to decrease late
      toxicity. Although proton therapy has been used for over five decades, most
      pediatric dosimetry studies and clinical series have been published over the last
      10 years. The purpose of this article is to review the physical, radiobiological
      and economic rationales for proton therapy in pediatric CNS malignancies, and
      provide an overview of the current challenges and future direction of research
      and utilization of this approach.

PMID- 25055022
TI  - Effectiveness of calcium hypochlorite on viral and bacterial contamination of
      alfalfa seeds.
AB  - Alfalfa sprouts have been involved in numerous foodborne outbreaks, which has
      increased the awareness for seed and sprout safety. This study compared the
      effectiveness of calcium hypochlorite (Ca(OCl)2) on the inactivation of bacteria
      and viruses on alfalfa seeds and in the presence of a simulated organic load.
      Alfalfa seeds were inoculated with human norovirus (huNoV) genogroup II (GII),
      murine norovirus (MNV), Tulane virus (TV), Escherichia coli O104:H4, and
      Salmonella enterica serovar Agona. Seeds were treated with Ca(OCl)2 (2000 ppm or
      20,000 ppm with the average of free chlorine 1388 +/- 117 mg/L and 11,472 +/-
      1500 mg/L, respectively, pH adjusted to 7.00). The reduction of huNoV genomic
      copies indicated that huNoV was relatively resistant to Ca(OCl)2 regardless of
      concentrations. Significant reductions were observed in the order of TV <
      Salmonella Agona < MNV < E. coli O104:H4 at 20,000 ppm Ca(OCl)2. A similar trend
      was found at 2000 ppm Ca(OCl)2 in the order of TV, Salmonella Agona, MNV < E.
      coli O104:H4. Ca(OCl)2 at 20,000 ppm was more effective than 2000 ppm for all the
      organisms tested. This trend was also observed in samples containing an
      artificial organic material load. Ca(OCl)2 activity on virus inactivation
      decreased as the organic load increased. Reduction was greater in fetal bovine
      serum-containing samples compared to alfalfa seeds, indicating a close
      relationship between the organisms and alfalfa seeds. Ca(OCl)2 could not
      completely inactivate bacteria or viruses inoculated on seeds, and high levels of
      E. coli O104:H4 and Salmonella Agona were present on sprouts from sanitized seed
      samples following a 7-day germination period.

PMID- 25055021
TI  - Treatment of glioblastoma in elderly patients.
AB  - Although glioblastoma occurs mostly in elderly patients, there is a paucity of
      trials addressing patients older than 70 years of age. Age, by itself,
      constitutes an unfavorable prognostic factor, which is probably due to
      unpropitious genetic features, but also due to iatrogenic defeatism. However,
      many retrospective studies report a survival benefit achieved by aggressive
      surgical resection seeking gross total removal of contrast-enhancing tumor
      according to preoperative MRI. Combined radiochemotherapy with concomitant and
      adjuvant temozolomide has not been investigated in prospective trials. Numerous
      retrospective studies and a meta-analysis suggest benefit from combined
      treatment. Prospective randomized trials only evaluated either temozolomide or
      radiotherapy. Single-treatment hypofractionated radiotherapy performed superior
      to conventional fractionation. In patients with methylated MGMT promoter, first
      line dose-dense temozolomide facilitates prolonged survival. However, there is no
      comparison with combined radiochemotherapy as the standard-of-care in adult
      patients. Comorbidity is more frequent in elderly patients, but does not
      correlate with preterm termination of temozolomide treatment. This review article
      compiles data proposing a straightforward glioblastoma treatment, irrespective of
      age.

PMID- 25055023
TI  - Coming to terms with the concept of moving species threatened by climate change -
      a systematic review of the terminology and definitions.
AB  - Intentional moving of species threatened by climate change is actively being
      discussed as a conservation approach. The debate, empirical studies, and policy
      development, however, are impeded by an inconsistent articulation of the idea.
      The discrepancy is demonstrated by the varying use of terms, such as assisted
      migration, assisted colonisation, or managed relocation, and their multiple
      definitions. Since this conservation approach is novel, and may for instance lead
      to legislative changes, it is important to aim for terminological consistency.
      The objective of this study is to analyse the suitability of terms and
      definitions used when discussing the moving of organisms as a response to climate
      change. An extensive literature search and review of the material (868 scientific
      publications) was conducted for finding hitherto used terms (N = 40) and
      definitions (N = 75), and these were analysed for their suitability. Based on the
      findings, it is argued that an appropriate term for a conservation approach
      relating to aiding the movement of organisms harmed by climate change is assisted
      migration defined as follows: Assisted migration means safeguarding biological
      diversity through the translocation of representatives of a species or population
      harmed by climate change to an area outside the indigenous range of that unit
      where it would be predicted to move as climate changes, were it not for
      anthropogenic dispersal barriers or lack of time. The differences between
      assisted migration and other conservation translocations are also discussed. A
      wide adoption of the clear and distinctive term and definition provided would
      allow more focused research on the topic and enable consistent implementation as
      practitioners could have the same understanding of the concept.

PMID- 25055024
TI  - The mechanism of proton translocation in respiratory complex I from molecular
      dynamics.
AB  - Respiratory complex I, the biggest enzyme of respiratory chain, plays a key role
      in energy production by the mitochondrial respiratory chain and has been
      implicated in many human neurodegenerative diseases. Recently, the crystal
      structure of respiratory complex I is reported. We perform 50 ns molecular
      dynamics simulations on the membrane domain of respiratory complex I under two
      hypothetical states (oxidized state and reduced state). We find that the density
      of water molecules in the trans-membrane domain under reduced state is bigger
      than that under oxidized state. The connecting elements (helix HL and beta
      hairpins-helix element) fluctuate stronger under reduced state than that under
      oxidized state, causing more internal water molecules and facilitating the proton
      conduction. The conformational changes of helix HL and the crucial charged
      residue Glu in TM5 play key roles in the mechanism of proton translocation. Our
      results illustrate the dynamic behavior and the potential mechanism of
      respiratory complex I, which provides the structural basis for drug design of
      respiratory complex I.

PMID- 25055025
TI  - Integrative analysis of ocular complications in atherosclerosis unveils pathway
      convergence and crosstalk.
AB  - Atherosclerosis is a life-threatening disease and a major cause of mortalities
      worldwide. While many of the atherosclerotic sequelae are reflected as
      microvascular effects in the eye, the molecular mechanisms of their development
      is not yet known. In this study, we employed a systems biology approach to unveil
      the most significant events and key molecular mediators of ophthalmic sequelae
      caused by atherosclerosis. Literature mining was used to identify the proteins
      involved in both atherosclerosis and ophthalmic diseases. A protein-protein
      interaction (PPI) network was prepared using the literature-mined seed nodes.
      Network topological analysis was carried out using Cytoscape, while network nodes
      were annotated using database for annotation, visualization and integrated
      discovery in order to identify the most enriched pathways and processes. Network
      analysis revealed that mitogen-activated protein kinase 1 (MAPK1) and protein
      kinase C occur with highest betweenness centrality, degree and closeness
      centrality, thus reflecting their functional importance to the network. Our
      analysis shows that atherosclerosis-associated ophthalmic complications are
      caused by the convergence of neurotrophin signaling pathways, multiple immune
      response pathways and focal adhesion pathway on the MAPK signaling pathway. The
      PPI network shares features with vasoregression, a process underlying multiple
      vascular eye diseases. Our study presents a first clear and composite picture of
      the components and crosstalk of the main pathways of atherosclerosis-induced
      ocular diseases. The hub bottleneck nodes highlight the presence of molecules
      important for mediating the ophthalmic complications of atherosclerosis and
      contain five established drug targets for future therapeutic modulation efforts. 

PMID- 25055026
TI  - Effective interaction studies for inhibition of DNA ligase protein from
      Staphylococcus aureus.
AB  - Staphylococcus aureus has been recognized as an important human pathogen for more
      than 100 years. It is among the most important causative agent of human
      infections in the twenty-first century. DNA ligase is the main protein
      responsible for the replication of S. aureus. In order to control the replication
      mechanism, DNA ligase is a successive drug target, hence we have chosen this
      protein for this study. We performed virtual screening using ZINC database for
      identification of potent inhibitor against DNA ligase. Based on the scoring
      methods, we have selected best five compounds from the ZINC database. In order to
      improve the accuracy, selected compounds were subjected into Quantum Polarized
      Ligand Docking (QPLD) docking, for which the results showed high docking score,
      compared to glide docking score. QPLD is more accurate as it includes charges in
      the scoring function, which was not available in the glide docking. Binding
      energy calculation results also indicated that selected compounds have good
      binding capacity with the target protein. In addition, these compounds on
      screening have good absorption, distribution, metabolism, excretion and toxicity
      property. In this study, we identified few compounds that particularly work
      against DNA ligase protein, having better interaction phenomenon and it would
      help further the experimental analysis. 

PMID- 25055027
TI  - Improving physical activity in daycare interventions.
AB  - BACKGROUND: The aim of the study was to objectively determine whether the
      Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) program
      improved physical activity levels during the school day. METHODS: The study
      compared the physical activity levels of subjects from 26 daycare centers,
      randomized into treatment (N=13) and control (N=13) groups. The subjects were 3
      to 5 year olds (N=209, 104 males and 105 females; age [years]=3.85+/-0.8 [mean+/
      standard deviation]), and accelerometry was used to determine the subjects'
      physical activity levels. Accelerometers were attached to each subject for 2 days
      before and immediately after a 6-month intervention. Height, mass, and waist were
      also measured. RESULTS: Regression analyses indicated that the treatment group
      demonstrated significant increases in moderate and vigorous physical activity, as
      compared to the control group (F(1, 207)=6.3, p<0.05, Cohen's d=0.30; F(1,
      207)=4.7, p<0.05, Cohen's d=0.25, respectively). The treatment group also showed
      significant increases in total physical activity (F(1, 218)=12.4; p<0.05) from
      pre- to post-test with significant increases in moderate and vigorous intensity
      physical activity (F(1, 218)=18.6, p<0.05; F(1, 218)=23.3, p<0.05, respectively).
      Regression analyses revealed significant increases in height for both groups from
      pre- to post-tests, but no differences were noted between groups. CONCLUSIONS:
      Implementation of the NAP SACC program in treatment daycare facilities resulted
      in significant increases in objectively measured physical activity levels,
      compared to the control group, demonstrating physical activity improvement in the
      treatment daycare centers.

PMID- 25055028
TI  - Base-catalyzed domino cyclization of acetylenes with ketones to functionalized
      cyclopentenes.
AB  - Acetylene reacts with methylaryl(hetaryl)ketones in the presence of 6.5 mol % KOH
      in DMSO to give diastereoselectively in single operationally functionalized
      cyclopentenes. This domino cyclization involving two molecules of acetylene and
      two molecules of ketone proceeds with the formation of four C-C bonds. The
      complementary assembly of the cyclopentenes with similar functionalities from
      acetylenes and 1,5-diketones has been developed. 

PMID- 25055029
TI  - In vitro synergistic activity of colistin and ceftazidime or ciprofloxacin
      against multidrug-resistant clinical strains of Pseudomonas aeruginosa.
AB  - Infections caused by multidrug resistant (MDR) Pseudomonas aeruginosa are
      difficult to treat. Antibiotic development is dwindling in recent years. In order
      to develop new alternate therapies antimicrobial activity of different antibiotic
      combinations are being studied in vitro and in vivo. Sub-inhibitory
      concentrations of colistin were tested in combination with ceftazidime or
      ciprofloxacin by the checkerboard method against 25 MDR strains of P. aeruginosa.
      Synergy was observed for ceftazidime or ciprofloxacin antibiotic combinations
      with colistin among 73.3% of MDR3 (R(AMK, GEN, TOB) R(CAZ) R(CIP)) strains and
      100% of MDR4 (R(AMK, GEN, TOB) R(CAZ) R(CIP) R(TZP)) strains. 6.6% strains of
      MDR3 and 14.3% strains of MDR5 (R(AMK, GEN, TOB) R(CAZ) R(CIP) R(TZP) R(IPM))
      phenotypes were inhibited by colistin and ceftazidime alone and 6.6% strains of
      MDR3 phenotypes were inhibited by colistin and ciprofloxacin alone. For the
      remaining strains, though synergy was not observed, significant reduction in
      minimum inhibitory concentration was evident. The results of this study are
      significant as sub-inhibitory concentrations of colistin have an advantage of
      reducing in vivo toxicity. These findings need further evaluation for clinical
      use.

PMID- 25055030
TI  - Evolution of wurtzite ZnO films on Cubic MgO (001) substrates: a structural,
      optical, and electronic investigation of the misfit structures.
AB  - We investigated the interface between hexagonal ZnO films and cubic MgO (001)
      substrates, fabricated via molecular beam epitaxy. X-ray diffraction and
      (scanning) transmission electron microscopy revealed that growth follows the
      single [0001] direction when the temperature of the substrate is above 200 
      degrees C, while when the substrate temperature is below 150  degrees C, growth
      initially is along [0001] and then mainly changes to [0-332] variants beyond a
      thickness of ~10 nm. Interestingly, a double-domain feature with a rotational
      angle of 30 degrees  appears during growth along [0001] regardless of the
      temperature, experimentally demonstrating the theoretical predictions for the
      occurrence of double rotational domains in such a heteroepitaxy [Grundmann et
      al., Phys. Rev. Lett. 105, 146102 (2010)]. We also found that the optical
      properties of the ZnO film are influenced greatly by the mutation of growth
      directions, stimulated by the bond-length modulations, as we determined from X
      ray absorption spectra at Zn K edge. These results also showed the evolution of
      the 4p(xy) and 4p(z) states in the conduction band with the rise in the
      temperature for growth. We consider that our findings may well promote the
      applications of ZnO in advanced optoelectronics for which its integration with
      other materials of different phases is desirable.

PMID- 25055031
TI  - Whey versus soy protein diets and renal status in rats.
AB  - Different dietary protein sources can promote different renal statuses. We
      examined the effects of whey protein (WP) and soy protein (SP) intake on plasma,
      urinary, and morphological renal parameters in rats. One hundred and twenty
      Wistar rats were randomly distributed into 2 experimental groups fed with either
      WP or SP diets over 12 weeks. These diets were based on commercial WP or SP
      isolates. The urinary calcium content was higher in the WP diet compared to the
      SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The
      urinary pH was more acidic in the WP diet group compared to the SP diet group
      (P<.001); however, no differences were observed between the groups for any of the
      renal morphological parameters analyzed (all, P>.05) or other plasma renal
      markers such as albumin or urea concentrations. The increase of acid and urinary
      calcium and the lower urinary citrate level observed in the WP diet group could
      increase the incidence of nephrolithiasis compared to the SP diet group. Despite
      the WP showed poorer acid-base profile, no significant morphological renal
      changes were observed. These results suggest that the use of SP instead of WP
      appears to promote a more alkaline plasma and urinary profile, with their
      consequent renal advantages.

PMID- 25055033
TI  - [Paraneoplastic syndromes and rheumatic diseases].
AB  - Paraneoplastic syndromes, which are discussed in this paper, are a heterogeneous
      group of disorders associated with cancer, but not directly caused by the
      physical effects of the primary tumor or its metastases. May precede the
      appearance of the malignant process, occur simultaneously or disclose in the
      course of cancer. Paraneoplastic syndromes may be caused directly by toxins
      produced by tumor cells, occur in the course of hypersensitivity reactions, or be
      the result of release of intracellular antigens. Due to the often similar
      systemic symptoms it is very important to evaluate the association of rheumatic
      diseases and cancer. Most paraneoplastic rheumatologic syndroms are difficult
      distinguishable from idiopathic rheumatologic disorders. The most common
      paraneoplastic syndromes include rheumatoid arthritis (RA)-like syndrome
      arthritis, inflammatory myopathies, hypertrophic osteoarthropathy, vasculitis and
      Raynaud's phenomenon. 

PMID- 25055032
TI  - Proteomic characterization of acyclovir-induced nephrotoxicity in a mouse model.
AB  - Acyclovir (ACV) is an effective and widely used antiviral agent. However, its
      clinical application is limited by severe nephrotoxicity. We assessed ACV-induced
      nephrotoxicity and identified the differentially expressed proteins using mass
      spectrometry-based proteomic analysis. In total, 30 ICR mice were
      intraperitoneally administrated ACV (150 or 600 mg/kg per day) for 9 days. After
      administration of ACV, levels of serum creatinine and urea nitrogen increased
      significantly. In addition, mouse kidneys exhibited histopathological changes and
      reduced expression levels of vascular endothelial growth factor (VEGF) and its
      receptor VEGFR2. In the proteomic analysis, more than 1,000 proteins were
      separated by two-dimensional polyacrylamide gel electrophoresis, and a total of
      20 proteins were up- or down-regulated in the ACV group compared with the saline
      group. Among these, six proteins (MHC class II antigen, glyoxalase 1,
      peroxiredoxin 1, alphaB-crystallin, fibroblast growth factor receptor 1-IIIb, and
      cytochrome c oxidase subunit Vb) were identified in association with ACV-induced
      nephrotoxicity. These findings were confirmed by Western blotting analysis. The
      differential expression levels of alpha-BC, Prx1, Glo I and CcO Vb suggest that
      oxidative damage and mitochondrial injury may be involved in ACV-induced
      nephrotoxicity. Furthermore, VEGF and FGF may play a role in tissue repair and
      the restoration process following ACV nephrotoxicity. 

PMID- 25055034
TI  - [Tc1-mediated contact sensitivity reaction, its mechanism and regulation].
AB  - The contact hypersensitivity reaction (CHS) to haptens is a classic example of
      cell-mediated immune response. In the effector phase, two stages can be
      distinguished: an early component, that appears only 2 hours after subsequent
      contact with the hapten, and the late component that develops approximately 24
      hours later which is mediated by TCRalphabeta+ cells. The effector lymphocytes
      may be CD4+ T helper 1 (Th1) cells or CD8+ T cytotoxic 1 (Tc1) cells, which
      depends on the employed hapten and/or mice strain. NKT lymphocytes play the
      crucial role in the CHS initiation, by supporting B1 cells in the antigen
      specific IgM antibodies production. The development of an early component is
      essential for the recruitment of T effector (Teff) cells to the side of hapten
      deposition and for the complete expansion of inflammatory reaction. The CHS
      reaction is under T regulatory (Treg) cells control, both in the induction phase
      as well as in the effector phase. A new view of a negative regulation of the Tc1
      mediated CHS response is based on the suppression induced by epicutaneous (EC)
      application of protein antigen. The DNP-BSA skin application, on a gauze patch,
      leads to a state of immunosuppression. This maneuver results in rising the
      population of Treg cells with TCRalphabeta+CD4+CD25+Foxp3+ phenotype. The
      mechanism of suppression requires direct contact between Treg cells and Teff
      cells and the participation of CTLA-4 molecule is also necessary. The described
      method of evoking immune tolerance via EC immunization may contribute to
      elaborate a new method of allergic contact dermatitis therapy. This is because of
      its effectiveness, ease of induction and non-invasive protein antigen
      application. 

PMID- 25055035
TI  - [Biosimilars in rheumatology and other fields of medicine].
AB  - Biosimilars are follow-up versions of innovative medicines with proved high
      similarity to the reference product. There may be some minor differences in
      clinically inactive components of a molecule which can be clinically significant,
      but they do not substantially affect the high resemblance to the original drug in
      their safety and potency. Introduction of the biosimilars brings hope to reduce
      the cost of treatment, so their availability will increase further as the
      expiration of patents on biotechnologically produced drugs will follow, which is
      currently taking place. There are new biosimilar drugs being introduced recently;
      these are monoclonal antibodies. They are much more structurally complicated
      compared to the first biotech drugs such as insulin, and their production
      processes are much more complex. Biosimilars as the end products of such
      sophisticated technology are affected by many variables. It is not possible to
      create "biogenerics," but only biosimilar drugs. Therefore, despite their
      similarities to the reference molecules, biosimilars are too different to forego
      clinical trials. Clinical trials of biosimilars need to be much broader than for
      generics, but they are limited compared to the reference biologicals' testing.
      Placebo controlled clinical trials are not required before registering a new
      biosimilar. Immunogenicity is a major source of concern related to biosimilars,
      although there may be the same problem with the original drugs. 

PMID- 25055036
TI  - [Base excision repair in Alzheimer's disease].
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease in people
      over 65 years of age. Estimates indicate that about 200 thousand Pole suffer from
      AD while in the world about 30 million people. Forecasts show that in developed
      countries the number of people with neurodegenerative diseases by 2025 will
      increase by several hundred percent compared to 1980. Results of carried out
      tests suggest several causes of this disease, in which an important role is
      played by age, genetic and environmental factors. An important role is played by
      oxidizing agents. They damage the genetic material and reduce activity of enzymes
      responsible for the repair of this damage contributing to the development of
      neurodegenerative diseases including AD. In this paper we discuss the
      relationship between the activity level of the main system removing oxidative DNA
      damage, named base excision repair (BER), which recognizes and repairs damaged
      DNA bases, as well as the key proteins involved in this type of DNA repair and
      AD. We also describe the important role of genetic polymorphism in genes encoding
      BER proteins, modulating the activity of this type of repair. This indicates the
      possibility to increase the knowledge of the AD mechanism based on the BER
      system, which may contribute to the identification of molecular markers of this
      disease in the future. 

PMID- 25055037
TI  - FGF21 expression and release in muscle cells: involvement of MyoD and regulation
      by mitochondria-driven signalling.
AB  - Although the liver is generally considered the main site of production of FGF21
      (fibroblast growth factor-21), high FGF21 levels have been found to be associated
      with neuromuscular mitochondrial genetic diseases, and there are indications that
      the muscle may be a relevant site of FGF21 production under conditions of
      muscular mitochondrial stress. In the present study, we found that expression and
      release of FGF21 was associated with myogenic differentiation, and we identified
      MyoD as a major controller of FGF21 gene transcription. Mimicking mitochondrial
      dysfunction using respiratory chain/oxidative phosphorylation inhibitors resulted
      in enhanced expression and release of FGF21 by muscle cells. The increased
      production of reactive oxygen species, subsequent induction of p38 MAPK (mitogen
      activated protein kinase) and activation of an ATF2 (activating transcription
      factor 2)-binding site at the proximal promoter region of the FGF21 gene was
      found to be a major mechanism linking mitochondrial dysfunction with enhanced
      FGF21 gene transcription in myogenic cells. The myogenic factor MyoD was required
      for the induction of FGF21 gene transcription by mitochondrial dysfunction, thus
      explaining the preferential response of muscle cells to mitochondrial dysfunction
      induced FGF21 expression and secretion. FGF21 release by muscle cells in response
      to mitochondrial alterations may represent a physiological mechanism by which the
      sensing of internal energetic status by muscles results in the release of FGF21
      to favour systemic metabolic adaptations. 

PMID- 25055039
TI  - The cost-effectiveness of different feeding patterns combined with prompt
      treatments for preventing mother-to-child HIV transmission in South Africa:
      estimates from simulation modeling.
AB  - OBJECTIVES: Based on the important changes in South Africa since 2009 and the
      Antiretroviral Treatment Guideline 2013 recommendations, we explored the cost
      effectiveness of different strategy combinations according to the South African
      HIV-infected mothers' prompt treatments and different feeding patterns. STUDY
      DESIGN: A decision analytic model was applied to simulate cohorts of 10,000 HIV
      infected pregnant women to compare the cost-effectiveness of two different HIV
      strategy combinations: (1) Women were tested and treated promptly at any time
      during pregnancy (Promptly treated cohort). (2) Women did not get testing or
      treatment until after delivery and appropriate standard treatments were offered
      as a remedy (Remedy cohort). Replacement feeding or exclusive breastfeeding was
      assigned in both strategies. Outcome measures included the number of infant HIV
      cases averted, the cost per infant HIV case averted, and the cost per life year
      (LY) saved from the interventions. One-way and multivariate sensitivity analyses
      were performed to estimate the uncertainty ranges of all outcomes. RESULTS: The
      remedy strategy does not particularly cost-effective. Compared with the untreated
      baseline cohort which leads to 1127 infected infants, 698 (61.93%) and 110
      (9.76%) of pediatric HIV cases are averted in the promptly treated cohort and
      remedy cohort respectively, with incremental cost-effectiveness of $68.51 and
      $118.33 per LY, respectively. With or without the antenatal testing and
      treatments, breastfeeding is less cost-effective ($193.26 per LY) than
      replacement feeding ($134.88 per LY), without considering the impact of
      willingness to pay. CONCLUSION: Compared with the prompt treatments, remedy in
      labor or during the postnatal period is less cost-effective. Antenatal HIV
      testing and prompt treatments and avoiding breastfeeding are the best strategies.
      Although encouraging mothers to practice replacement feeding in South Africa is
      far from easy and the advantages of breastfeeding can not be ignored, we still
      suggest choosing replacement feeding as far as possible.

PMID- 25055040
TI  - Protein distributions from a stochastic model of the lac operon of E. coli with
      DNA looping: analytical solution and comparison with experiments.
AB  - Although noisy gene expression is widely accepted, its mechanisms are subjects of
      debate, stimulated largely by single-molecule experiments. This work is concerned
      with one such study, in which Choi et al., 2008, obtained real-time data and
      distributions of Lac permease in E. coli. They observed small and large protein
      bursts in strains with and without auxiliary operators. They also estimated the
      size and frequency of these bursts, but these were based on a stochastic model of
      a constitutive promoter. Here, we formulate and solve a stochastic model
      accounting for the existence of auxiliary operators and DNA loops. We find that
      DNA loop formation is so fast that small bursts are averaged out, making it
      impossible to extract their size and frequency from the data. In contrast, we can
      extract not only the size and frequency of the large bursts, but also the
      fraction of proteins derived from them. Finally, the proteins follow not the
      negative binomial distribution, but a mixture of two distributions, which reflect
      the existence of proteins derived from small and large bursts. 

PMID- 25055041
TI  - A pruritic, reticulated bullous eruption in a healthy young man.

PMID- 25055042
TI  - Mechanics of graphyne crumpling.
AB  - The recent capability of synthesizing large-scale crumpled graphene-related 2D
      materials has motivated intensive efforts to boost its promising applications in
      electronics, energy storage, composites and biomedicine. As deformation of
      graphene-related 2D materials can strongly affect their properties and the
      performance of graphene-based devices and materials, it is highly desirable to
      attain subtle control of reversible wrinkling and crumpling of graphene.
      Graphyne, a 2D lattice of sp(2)- and sp(1)-hybridized carbons similar to
      graphene, has remained unexplored with respect to its crumpling behavior. Here we
      employ molecular dynamics simulation to explore the behavior of graphynes under
      geometric confinement across various temperatures, sizes, and crumpling rates and
      compare them to graphene under the same conditions, with a focus on the
      mechanical stabilizing mechanisms and properties of the crumpled structures. The
      lower density of graphynes creates less deformation-induced bending energy than
      graphene; as such the graphynes exhibit a markedly increased propensity for
      stable crumpling. It is also shown that the crumpled 2D carbon materials
      demonstrate the hardness and bulk modulus of an equivalent magnitude with
      crumpled graphene, with the most important behavior-determining factor being the
      number of linking sp(1)-hybridized carbons in the material. Our results show that
      irrespective of the initial geometry and crumpling rate, the final structures
      present intriguing and useful properties which can be incorporated into crumpled
      graphene structures. 

PMID- 25055043
TI  - Advances in the understanding and behavioural management of sexual dysfunctions.
AB  - PURPOSE OF REVIEW: Sexual medicine is a branch often neglected by professionals
      from different specialties associated with it. However, research in this field
      has picked up in recent years, owing to recently renewed interest in upholding
      the sexual rights of the population in general and lesbian, gay, bisexual and
      transgender groups in particular. The recently released Diagnostic and
      statistical manual of mental disorders, fifth edition, by the American
      Psychiatric Association in May 2013 has stirred up the supporters and critics (of
      Diagnostic and statistical manual of mental disorders, fifth edition) alike.
      RECENT FINDINGS: Diagnostic and statistical manual of mental disorders, fifth
      edition, has updated diagnostic criteria for some of the sexual disorders to
      improve understanding and diagnostic validity. Certain sexual dysfunctions have
      been regrouped and sexual response cycle-based classification has been partially
      withdrawn. Research in the area of behavioral management of sexual dysfunctions
      has given some novel concepts, particularly for women. SUMMARY: Although
      improvements in behavioral management (of sexual dysfunctions) and
      classification/diagnostic criteria in Diagnostic and statistical manual of mental
      disorders, fifth edition, is a step forward in the field of sexual medicine, we
      need to further improve our understanding in many of the lacunae, still bearing
      on the field of sexual medicine, lest we may fall at the first hurdle.

PMID- 25055044
TI  - Snail-regulated MiR-375 inhibits migration and invasion of gastric cancer cells
      by targeting JAK2.
AB  - MicroRNAs (miRNAs) have been reported to play a critical role in cancer invasion
      and metastasis. Our previous study showed that miR-375 frequently downregulated
      in gastric cancer suppresses cell proliferation by targeting Janus kinase 2
      (JAK2). Here, we further found that the expression level of miR-375 is
      significantly decreased in metastatic gastric cancer tissues compared with the
      non-metastasis controls. Ectopic expression of miR-375 inhibits the migration and
      invasion of gastric cancer cells partially by targeting JAK2. Furthermore, miR
      375 expression is negatively regulated by the metastasis associated transcription
      factor Snail, which directly binds to the putative promoter of miR-375. Moreover,
      overexpression of Snail can partially reverse the inhibition of gastric cancer
      cell migration caused by miR-375. Taken together, these data suggest that miR-375
      may be negatively regulated by Snail and involved in gastric cancer cell
      migration and invasion potentially by targeting JAK2. 

PMID- 25055045
TI  - Ultrastructure of human tracheal smooth muscle from subjects with asthma and
      nonasthmatic subjects. Standardized methods for comparison.
AB  - A characteristic feature of asthma is exaggerated airway narrowing, termed airway
      hyper-responsiveness (AHR) due to contraction of airway smooth muscle (ASM).
      Although smooth muscle (SM)-specific asthma susceptibility genes have been
      identified, it is not known whether asthmatic ASM is phenotypically different
      from nonasthmatic ASM in terms of subcellular structure or mechanical function.
      The present study is the first to systematically quantify, using electron
      microscopy, the ultrastructure of tracheal SM from subjects with asthma and
      nonasthmatic subjects. Methodological details concerning tissue sample
      preparation, ultrastructural quantification, and normalization of isometric force
      by appropriate morphometric parameters are described. We reasoned that genetic
      and/or acquired differences in the ultrastructure of asthmatic ASM could be
      associated with functional changes. We recently reported that asthmatic ASM is
      better able to maintain and recover active force generation after length
      oscillations simulating deep inspirations. The present study was designed to seek
      structural evidence to account for this observation. Contrary to our hypotheses,
      no significant qualitative or quantitative differences were found in the
      subcellular structure of asthmatic versus nonasthmatic tracheal SM. Specifically,
      there were no differences in average SM cell cross-sectional area; fraction of
      the cell area occupied by nonfilamentous area; amounts of mitochondria, dense
      bodies, and dense plaques; myosin and actin filament densities; basal lamina
      thickness; and the number of microtubules. These results indicate that functional
      differences in ASM do not necessarily translate into observable structural
      changes. 

PMID- 25055046
TI  - Voice disorders in mucosal leishmaniasis.
AB  - INTRODUCTION: Leishmaniasis is considered as one of the six most important
      infectious diseases because of its high detection coefficient and ability to
      produce deformities. In most cases, mucosal leishmaniasis (ML) occurs as a
      consequence of cutaneous leishmaniasis. If left untreated, mucosal lesions can
      leave sequelae, interfering in the swallowing, breathing, voice and speech
      processes and requiring rehabilitation. OBJECTIVE: To describe the anatomical
      characteristics and voice quality of ML patients. MATERIALS AND METHODS: A
      descriptive transversal study was conducted in a cohort of ML patients treated at
      the Laboratory for Leishmaniasis Surveillance of the Evandro Chagas National
      Institute of Infectious Diseases-Fiocruz, between 2010 and 2013. The patients
      were submitted to otorhinolaryngologic clinical examination by endoscopy of the
      upper airways and digestive tract and to speech-language assessment through
      directed anamnesis, auditory perception, phonation times and vocal acoustic
      analysis. The variables of interest were epidemiologic (sex and age) and clinic
      (lesion location, associated symptoms and voice quality. RESULTS: 26 patients
      under ML treatment and monitored by speech therapists were studied. 21 (81%) were
      male and five (19%) female, with ages ranging from 15 to 78 years (54.5+15.0
      years). The lesions were distributed in the following structures 88.5% nasal,
      38.5% oral, 34.6% pharyngeal and 19.2% laryngeal, with some patients presenting
      lesions in more than one anatomic site. The main complaint was nasal obstruction
      (73.1%), followed by dysphonia (38.5%), odynophagia (30.8%) and dysphagia
      (26.9%). 23 patients (84.6%) presented voice quality perturbations. Dysphonia was
      significantly associated to lesions in the larynx, pharynx and oral cavity.
      CONCLUSION: We observed that vocal quality perturbations are frequent in patients
      with mucosal leishmaniasis, even without laryngeal lesions; they are probably
      associated to disorders of some resonance structures (larynx, pharynx and nasal
      and oral cavities) or even to compensation mechanisms caused by the presence of
      lesions in the upper airways and digestive tract.

PMID- 25055048
TI  - Statin therapy in women.
AB  - The 2013 American College of Cardiology/American Heart Association guidelines on
      the treatment of cholesterol recommend therapy for patients with (1) known
      cardiovascular disease (CVD); (2) low-density lipoprotein cholesterol (LDL-C) of
      190 mg/dL or higher; (3) type 1 or type 2 diabetes mellitus and LDL-C between 70
      mg/dL and 189 mg/dL (for ages 40-75); and 4) LDL-C between 70 mg/dL and 189 mg/dL
      and an estimated 10-year cardiovascular risk >=7.5% (for ages 40-75), using their
      new risk calculator. Although statin therapy is indicated for women at elevated
      risk of CVD, safety concerns related to glucose elevations and myalgias may
      outweigh benefits for women at low absolute risk of CVD.

PMID- 25055047
TI  - Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G.
AB  - TCAP encoded telethonin is a 19 kDa protein, which plays an important role in
      anchoring titin in Z disc of the sarcomere, and is known to cause LGMD2G, a rare
      muscle disorder characterised by proximal and distal lower limb weakness, calf
      hypertrophy and loss of ambulation. A total of 300 individuals with ARLGMD were
      recruited for this study. Among these we identified 8 clinically well
      characterised LGMD2G cases from 7 unrelated Dravidian families. Clinical
      examination revealed predominantly proximo-distal form of weakness, scapular
      winging, muscle atrophy, calf hypertrophy and foot drop, immunoblot showed either
      complete absence or severe reduction of telethonin. Genetic analysis revealed a
      novel nonsense homozygous mutation c.32C>A, p.(Ser11*) in three patients of a
      consanguineous family and an 8 bp homozygous duplication c.26_33dupAGGTGTCG,
      p.(Arg12fs31*) in another patient. Both mutations possibly lead to truncated
      protein or nonsense mediated decay. We could not find any functionally
      significant TCAP mutation in the remaining 6 samples, except for two other
      polymorphisms, c.453A>C, p.( = ) and c.-178G>T, which were found in cases and
      controls. This is the first report from India to demonstrate TCAP association
      with LGMD2G.

PMID- 25055050
TI  - Endocrine disruption screening by protein and gene expression of vitellogenin in
      freshly isolated and cryopreserved rainbow trout hepatocytes.
AB  - Xenobiotics may activate the estrogen receptor, resulting in alteration of normal
      endocrine functions in animals and humans. Consequently, this necessitates
      development of assay end points capable of identifying estrogenic xenobiotics. In
      the present study, we screened the potential estrogenicity of chemicals via their
      ability to induce vitellogenin (VTG) expression in cultured primary hepatocytes
      from male trout. A routine method for VTG detection measures the secretion of the
      protein by enzyme-linked immunosorbent assay (ELISA) in freshly isolated trout
      hepatocytes. However, this lengthy (6 days) culturing procedure requires that
      hepatocyte isolation is performed each time the assay is run. We optimized this
      methodology by investigating the utility of cryopreserved hepatocytes, shortening
      the incubation time, performing a quantitative real-time PCR (qPCR) method for
      VTG quantification, and verifying the model system with reference chemicals
      17beta-estradiol, estrone, diethylstilbestrol, hexestrol, genistein, and a
      negative control, corticosterone. To test the performance of both freshly
      isolated and cryopreserved hepatocytes, mRNA was collected from hepatocytes
      following 24 h treatment for VTG gene expression analysis, whereas cell culture
      media was collected for a VTG ELISA 96 h post-treatment. EC50 values were
      obtained for each reference chemical except for corticosterone, which exhibited
      no induction of VTG gene or protein level. Our results show linear concordance
      between ELISA and qPCR detection methods. Although there was approximately 50%
      reduction in VTG inducibility following cryopreservation, linear concordance of
      EC50 values was found between freshly isolated and cryopreserved hepatocytes,
      indicating that cryopreservation does not alter the functional assessment of
      estrogen receptor activation and therefore VTG expression. These studies
      demonstrate that qPCR is a sensitive and specific method for detecting VTG gene
      expression that can be used together with cryopreserved trout hepatocytes for
      screening estrogenic chemicals, resulting in a reduction of the time required to
      perform the assay and enabling greater access to the model system through the
      approach of cryopreservation. 

PMID- 25055049
TI  - Metal-ion effects on the polarization of metal-bound water and infrared
      vibrational modes of the coordinated metal center of Mycobacterium tuberculosis
      pyrazinamidase via quantum mechanical calculations.
AB  - Mycobacterium tuberculosis pyrazinamidase (PZAse) is a key enzyme to activate the
      pro-drug pyrazinamide (PZA). PZAse is a metalloenzyme that coordinates in vitro
      different divalent metal cofactors in the metal coordination site (MCS). Several
      metals including Co(2+), Mn(2+), and Zn(2+) are able to reactivate the metal
      depleted PZAse in vitro. We use quantum mechanical calculations to investigate
      the Zn(2+), Fe(2+), and Mn(2+) metal cofactor effects on the local MCS structure,
      metal-ligand or metal-residue binding energy, and charge distribution. Results
      suggest that the major metal-dependent changes occur in the metal-ligand binding
      energy and charge distribution. Zn(2+) shows the highest binding energy to the
      ligands (residues). In addition, Zn(2+) and Mn(2+) within the PZAse MCS highly
      polarize the O-H bond of coordinated water molecules in comparison with Fe(2+).
      This suggests that the coordination of Zn(2+) or Mn(2+) to the PZAse protein
      facilitates the deprotonation of coordinated water to generate a nucleophile for
      catalysis as in carboxypeptidase A. Because metal ion binding is relevant to
      enzymatic reaction, identification of the metal binding event is important. The
      infrared vibrational mode shift of the C?Nepsilon (His) bond from the M.
      tuberculosis MCS is the best IR probe to metal complexation. 

PMID- 25055051
TI  - Interrogation of allelic chromatin states in human cells by high-density ChIP
      genotyping.
AB  - Allele-specific (AS) assessment of chromatin has the potential to elucidate
      specific cis-regulatory mechanisms, which are predicted to underlie the majority
      of the known genetic associations to complex disease. However, development of
      chromatin landscapes at allelic resolution has been challenging since sites of
      variable signal strength require substantial read depths not commonly applied in
      sequencing based approaches. In this study, we addressed this by performing
      parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high
      density Illumina genotyping arrays. Allele-specificity for the histone
      modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed
      using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS
      ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq
      sites. We observed characteristic patterns of allelic-imbalance for each histone
      modification around allele-specifically expressed transcripts. Notably, we found
      H3K4me1 to be significantly anti-correlated with allelic expression (AE) at
      transcription start sites, indicating H3K4me1 allelic imbalance as a marker of
      AE. We also found that allelic chromatin domains exhibit population and cell-type
      specificity as well as heritability within trios. Finally, we observed that a
      subset of allelic chromatin domains is regulated by DNase I-sensitive
      quantitative trait loci and that these domains are significantly enriched for
      genome-wide association studies hits, with autoimmune disease associated SNPs
      specifically enriched in lymphoblasts. This study provides the first genome-wide
      maps of allelic-imbalance for five histone marks. Our results provide new
      insights into the role of chromatin in cis-regulation and highlight the need for
      high-depth sequencing in ChIP-seq studies along with the need to improve allele
      specificity of ChIP-enrichment. 

PMID- 25055052
TI  - Accumulation and molecular regulation of anthocyanin in purple tumorous stem
      mustard (Brassica juncea var. tumida Tsen et Lee).
AB  - Tumorous stem mustard (Brassica juncea var. tumida Tsen et Lee) is an
      economically and nutritionally important dietary vegetable in Asian countries.
      Purple tumorous stem mustard contains inflated tumorous stem and abundant
      anthocyanin accumulation in leaves. Here, 20 anthocyanins were separated and
      identified from the purple tumorous stem mustard by high-performance liquid
      chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS).
      In order to investigate the regulatory anthocyanin production in purple tumorous
      stem mustard, the expression of anthocyanin biosynthetic and regulatory genes in
      leaves from purple and green cultivars were examined. Regulatory gene BjTT8 and
      all biosynthetic genes were dramatically upregulated in the purple variety.
      Moreover, the transcript level of BjTT8 and all structural genes, except BjPAL,
      were all significantly higher in light-treated sprouts than in the dark. These
      results indicate that transcriptional activation of BjTT8 is associated with
      upregulation of most anthocyanin biosynthetic genes, to produce anthocyanins in
      purple tumorous stem mustard. 

PMID- 25055054
TI  - Modeling of simultaneous anaerobic methane and ammonium oxidation in a membrane
      biofilm reactor.
AB  - Nitrogen removal by using the synergy of denitrifying anaerobic methane oxidation
      (DAMO) and anaerobic ammonium oxidation (Anammox) microorganisms in a membrane
      biofilm reactor (MBfR) has previously been demonstrated experimentally. In this
      work, a mathematical model is developed to describe the simultaneous anaerobic
      methane and ammonium oxidation by DAMO and Anammox microorganisms in an MBfR for
      the first time. In this model, DAMO archaea convert nitrate, both externally fed
      and/or produced by Anammox, to nitrite, with methane as the electron donor.
      Anammox and DAMO bacteria jointly remove the nitrite fed/produced, with ammonium
      and methane as the electron donor, respectively. The model is successfully
      calibrated and validated using the long-term (over 400 days) dynamic experimental
      data from the MBfR, as well as two independent batch tests at different
      operational stages of the MBfR. The model satisfactorily describes the methane
      oxidation and nitrogen conversion data from the system. Modeling results show the
      concentration gradients of methane and nitrogen would cause stratification of the
      biofilm, where Anammox bacteria mainly grow in the biofilm layer close to the
      bulk liquid and DAMO organisms attach close to the membrane surface. The low
      surface methane loadings result in a low fraction of DAMO microorganisms, but the
      high surface methane loadings would lead to overgrowth of DAMO bacteria, which
      would compete with Anammox for nitrite and decrease the fraction of Anammox
      bacteria. The results suggest an optimal methane supply under the given condition
      should be applied not only to benefit the nitrogen removal but also to avoid
      potential methane emissions. 

PMID- 25055053
TI  - A variational eigenvalue solver on a photonic quantum processor.
AB  - Quantum computers promise to efficiently solve important problems that are
      intractable on a conventional computer. For quantum systems, where the physical
      dimension grows exponentially, finding the eigenvalues of certain operators is
      one such intractable problem and remains a fundamental challenge. The quantum
      phase estimation algorithm efficiently finds the eigenvalue of a given
      eigenvector but requires fully coherent evolution. Here we present an alternative
      approach that greatly reduces the requirements for coherent evolution and combine
      this method with a new approach to state preparation based on ansatze and
      classical optimization. We implement the algorithm by combining a highly
      reconfigurable photonic quantum processor with a conventional computer. We
      experimentally demonstrate the feasibility of this approach with an example from
      quantum chemistry--calculating the ground-state molecular energy for He-H(+). The
      proposed approach drastically reduces the coherence time requirements, enhancing
      the potential of quantum resources available today and in the near future.

PMID- 25055055
TI  - Time-resolved measurements of the optical properties of fibrous media using the
      anisotropic diffusion equation.
AB  - Transmittance and reflectance from spruce wood and bovine ligamentum nuchae as
      two different fibrous media are examined by time-of-flight spectroscopy for
      varying source detector separations and several orientations of the fibers in the
      sample. The anisotropic diffusion theory is used to obtain the absorption
      coefficient and the diffusion coefficients parallel and perpendicular to the
      fibers. The results are compared to those obtained with the isotropic diffusion
      theory. It is shown that for increasing source detector separations, the
      retrieved optical properties change as expected from Monte Carlo simulations
      performed in a previous study. This confirms that the anisotropic diffusion
      theory yields useful results for certain experimental conditions.

PMID- 25055056
TI  - Label-free immunodetection of the cancer biomarker CA125 using high-Deltan liquid
      crystals.
AB  - A label-free and array-based optical liquid-crystal (LC) immunodetection
      technique for the detection of CA125 antigen, a protein biomarker most frequently
      used for ovarian cancer detection, was demonstrated with a nematic LC with larger
      birefringence (Deltan) to promote sensitivity in detecting biomolecules. The LC
      based immunodetection offers an alternative and sensitive approach for the
      detection of biomarker proteins, with the potential of replacing conventional
      immunoassays used in biochemical studies and clinical laboratories.

PMID- 25055057
TI  - Effect of olfactory stimulation by fresh rose flowers on autonomic nervous
      activity.
AB  - OBJECTIVE: To clarify the effect of olfactory stimulation by fresh rose flowers,
      which exude a strong fragrance, on heart rate variability. SETTINGS: A chamber
      with an artificial climate maintained at 25 degrees C with 50% relative humidity
      and 230 lux illumination at the Center for Environment, Health, and Field
      Sciences, Chiba University, Japan. PARTICIPANTS: Nineteen female university and
      graduate students (mean age, 21.6+/-1.5 years; age range, 19.0-26.0 years).
      INTERVENTIONS: Fresh rose flowers as an olfactory stimulant, with air as a
      control. OUTCOME MEASURES: Heart rate variability and subjective evaluations. The
      power levels of the high-frequency (HF) (0.15-0.40 Hz) and low-frequency (LF)
      (0.04-0.15 Hz) components of heart rate variability were calculated by the
      maximum-entropy method. The HF power was considered to reflect parasympathetic
      nervous activity. The LF/HF power ratio was determined to reflect the sympathetic
      nervous activity. A modified semantic differential method was used to perform
      subjective evaluations. RESULTS: Fresh rose flowers induced (1) a significant
      increase in parasympathetic nervous activities and (2) an increase in
      "comfortable" and "natural" feelings. CONCLUSION: The findings indicated that
      olfactory stimulation by fresh rose flowers induced physiological and
      psychological relaxation.

PMID- 25055058
TI  - Deep anterior lamellar keratoplasty versus penetrating keratoplasty for treating
      keratoconus.
AB  - BACKGROUND: Keratoconus is an ectatic (weakening) disease of the cornea, which is
      the clear surface at the front of the eye. Approximately 10% to 15% of patients
      diagnosed with keratoconus require corneal transplantation. This may be full
      thickness (penetrating) or partial-thickness (lamellar). OBJECTIVES: To compare
      visual outcomes after deep anterior lamellar keratoplasty (DALK) and penetrating
      keratoplasty for keratoconus, and to compare additional outcomes relating to
      factors which may contribute to poor visual outcomes (e.g. astigmatism, graft
      rejection and failure). SEARCH METHODS: We searched a number of electronic
      databases including CENTRAL, PubMed and EMBASE without using any date or language
      restrictions. We last searched the electronic databases on 31 October 2013. We
      also handsearched the proceedings of several international ophthalmic
      conferences. SELECTION CRITERIA: We included all randomised controlled trials
      (RCTs) comparing the outcomes of DALK and penetrating keratoplasty in the
      treatment of keratoconus. DATA COLLECTION AND ANALYSIS: Two authors assessed
      trial quality and extracted data independently. For dichotomous data (graft
      failure, rejection, achievement of functional vision) results were expressed as
      odds ratios (ORs) and 95% confidence intervals (CIs). For continuous data
      (postoperative best corrected visual acuity (BCVA), uncorrected visual acuity
      (UCVA), keratometric astigmatism and spherical equivalent) results were expressed
      as mean differences (MDs) and 95% CIs. MAIN RESULTS: We identified two completed
      studies, with a total of 111 participants (n = 30 and n = 81), both conducted in
      Iran, that met our inclusion criteria. Participants had moderate to severe
      keratoconus pre-operatively and were randomly allocated to receive either DALK or
      penetrating keratoplasty. Only one eye of each participant was treated as part of
      the trials. The smaller study had 12 month follow-up data for all participants.
      For the larger study, four DALK surgeries had to be abandoned due to technical
      failure and visual and refractive outcomes were not measured in these
      participants. Follow-up length for the remaining 77 participants ranged from 6.8
      to 36.4 months, with all 77 followed for at least three months post-suture
      removal. Details of the randomisation procedure were unavailable for the smaller
      study and so sensitivity analyses were conducted to determine if the results from
      this study had affected the overall results of the review.Neither of the included
      studies reported a difference between groups on any of the measures of post-graft
      visual achievement, keratometric astigmatism or spherical equivalent. A single
      case of graft failure in a penetrating keratoplasty was reported. No
      postoperative graft failures were reported in the DALK group of either
      study.Instances of graft rejection were reported in both groups, in both studies.
      The majority of these cases were successfully treated with steroids. The data,
      which related to all cases in each study - given that the four cases that did not
      go ahead as planned had already technically failed without presence of rejection 
      showed that rejection was less likely to occur in DALK (odds ratio (OR): 0.33,
      95% confidence interval (CI) 0.14 to 0.81, GRADE rating: moderate).Results of the
      sensitivity analysis indicated that inclusion of the Razmju 2011 study did not
      bias the results with regards to rejection episodes. While sensitivity analysis
      showed altered results with regards to failure rates, the data available from the
      Javadi 2010 study alone had a very wide 95% CI, suggesting an imprecise estimate.
      Therefore, even after removal of the Razmju 2011 data, it is still difficult to
      draw conclusions regarding superiority of one technique over another with regards
      to graft failure.DALK was unable to be completed as planned in four cases and in
      a further three cases, complications during dissection required further
      intervention. Other adverse events, of varying severity, were reported in both
      intervention groups with similar frequency. For both types of surgery, these
      included postoperative astigmatism, steroid induced ocular hypertension and
      persistent epithelial defects. In recipients of DALK, one participant had
      interface neovascularisation (a proliferation of blood vessels where the host and
      donor cornea come together) and one had wrinkling of Descemet's membrane, the
      basement membrane separating the corneal stroma from the corneal endothelium. In
      the penetrating keratoplasty groups, one participant required graft resuturing
      and one had an atonic pupil, a condition in which the pupil dilates and is non
      reactive.Overall, the quality of the evidence was rated as very low to moderate,
      with methodological limitations, incomplete data analysis and imprecision of
      findings, as well as high risk of bias in several areas for both studies.
      AUTHORS' CONCLUSIONS: We found no evidence to support a difference in outcomes
      with regards to BCVA at three months post-graft or at any of the other time
      points analysed (GRADE rating: very low). We also found no evidence of a
      difference in outcomes with regards to graft survival, final UCVA or keratometric
      outcomes. We found some evidence that rejection is more likely to occur following
      penetrating keratoplasty than DALK (GRADE rating: moderate). The small number of
      studies included in the review and methodological issues relating to the two,
      mean that the overall quality of the evidence in this review is low. There is
      currently insufficient evidence to determine which technique may offer better
      overall outcomes - final visual acuity and time to attain this, keratometric
      stabilisation, risk of rejection or failure, or both, and risk of other adverse
      events - for patients with keratoconus. Large randomised trials comparing the
      outcomes of penetrating keratoplasty and DALK in the treatment of keratoconus are
      needed.

PMID- 25055059
TI  - Evidence for an exclusive association of matrix metalloproteinase-9 with
      dysfunctional high-density lipoprotein: a novel finding.
AB  - OBJECTIVE: High-density lipoprotein is a heterogeneous class of lipoprotein with
      diverse antiatherogenic functions. However, these antiatherogenic properties of
      HDL can be compromised in atherosclerotic conditions. We have recently identified
      dysfunctionality in HDL even among healthy subjects, during systemic
      inflammation. This study was carried out with the objective of examining whether
      dysfunctional HDL is associated with pro-inflammatory proteins other than the
      acute phase proteins as reported earlier. METHODS: Serum HDL was isolated by
      three different methods-density gradient ultracentrifugation, PEG precipitation
      and electroelution. The antioxidant property of HDL was assessed as change in
      oxidation of LDL based on Dichloro-dihydro-fluorescein diacetate assay. HDL was
      subjected to gelatin zymography and western blot for assessment of MMP 9
      activity. RESULTS: Dysfunctional HDL did not prevent the auto-oxidation of LDL.
      On the contrary the oxidation was enhanced. The zymogram data indicated enhanced
      MMP-9 activity selectively in dysfunctional HDL, irrespective of HDL isolation
      methods. This was confirmed by western blot of HDL probed with antibody specific
      to MMP 9. We also observed that dysfunctional HDL induced inflammatory response
      in monocyte/macrophages as evidenced by enhanced TNF-alpha and decreased IL-10
      production. Further, invitro incubation of functional HDL with MMP-9 provided
      direct evidence for the association of MMP-9 with HDL and the role of MMP-9 in
      HDL dysfunction. CONCLUSION: A remarkable finding in the present study is the
      previously unrecognized association of MMP-9 with dysfunctional HDL and its
      proinflammatory property, indicating a novel molecular connection that can
      enhance the risk of cardiovascular disease in subjects with dysfunctional HDL.

PMID- 25055060
TI  - Eosinophils count and periprocedural myocardial infarction in patients undergoing
      percutaneous coronary interventions.
AB  - BACKGROUND: Eosinophils have been involved in a wide spectrum of pro-inflammatory
      and pro-thrombotic conditions, with the development of cardiovascular
      complications in a significant proportion of hypereosinophilic patients. However,
      no study has so far evaluated the impact of eosinophils levels on periprocedural
      myocardial infarction (PMI) in patients undergoing non-urgent percutaneous
      coronary interventions (PCI), that was, then, aim of current study. METHODS: In a
      consecutive cohort of patients, myonecrosis biomarkers were dosed at intervals
      from 6 to 48 h after PCI. Periprocedural myonecrosis was defined as troponin I
      increase by 3 times the ULN or by 50% of an elevated baseline value, whereas PMI
      as CKMB increase by 3 times the ULN or 50% of baseline. RESULTS: Our population
      is represented by 1543 patients who were divided according to tertiles of
      absolute eosinophils count (AEC <= 0.1; 0.1-0.2; >0.2 * 10^3/ml). Higher AEC was
      related to male gender (p = 0.002), arterial hypertension (p = 0.02), diabetes (p
      = 0.001), previous coronary revascularization (p = 0.003 for PCI, p = 0.03 for
      CABG), treatment with ARBs, beta-blockers, diuretics and ASA (p < 0.001), statins
      (p = 0.02), calcium antagonists (p = 0.05), glycosylated hemoglobin (p < 0001),
      creatinine levels (p = 0.001) and platelet count (p = 0.01), while inversely with
      acute presentation (p < 0.001), glycemia (p = 0.03), HDL-cholesterol and C
      reactive protein (p = 0.02). AEC related with multivessel coronary artery disease
      (p = 0.05), lesion length (p = 0.01), drug eluting stents implantation (p =
      0.001) and use of kissing balloon technique (p = 0.05), while inversely to
      intracoronary thrombus (p < 0.001) and thrombectomy (p = 0.04). AEC did not
      influence the occurrence of PMI (p = 0.06, adjusted OR [95% CI] = 1.06 [0.86
      1.31], p = 0.57) or myonecrosis (p = 0.15, adjusted OR [95% CI] = 1.06 [0.88
      1.27], p = 0.53). Results were confirmed at subgroup analysis in higher-risk
      subsets of patients. CONCLUSION: In patients undergoing non-urgent PCI,
      eosinophils levels are not associated with the occurrence of periprocedural
      myocardial infarction or myonecrosis.

PMID- 25055061
TI  - Evaluation of biocompatibility of the AC8 peptide and its potential use as a drug
      carrier.
AB  - Peptide-based nanoparticles have emerged as promising drug delivery systems for
      targeted cancer therapy. Yet, the biocompatibility of these nanoparticles has not
      been elucidated. Here, the in vitro biocompatibility and toxicity and in vivo
      immunocompatibility and bioactivity of the self/coassembling peptide AC8 in its
      nanoparticle form are evaluated. AC8 showed minimal hemolytic activity (5%) and
      did not cause aggregation of red blood cells. The in vitro assay revealed that
      AC8 did not activate the complement system via the classical or alternative
      pathway but did activate the lectin pathway to a small extent. However, AC8
      showed no C3a and C5a anaphylotoxin activation suggesting that complement
      activation did not proceed to the later, inflammatory, stages. The in vivo immune
      response assay showed that administration of AC8 to BALB/c mice had no effect on
      the weight of immune organs or body weight of mice at doses less than 0.1 mg/kg.
      This peptide also did not have any effect on the expression of CD3+ T-cells and
      natural killer (NK) cells, the ratio of CD4+/CD8+ T-cell, and the proliferation
      of B-cells. These results suggest that AC8 can be a potential carrier candidate
      for drug delivery. 

PMID- 25055062
TI  - Oriented aggregation of lepidocrocite and impact on surface charge development.
AB  - The impact of lepidocrocite (gamma-FeOOH) nanoparticle aggregation on mineral
      surface charge development was resolved in aqueous solutions of NaCl and NaClO4.
      Synthetic rod-like particles exhibiting charged edge (100) and neutrally/low
      charged (010) faces self-aggregated in salt-free solutions. Aggregation was
      notably imaged by high-resolution transmission electron microscopy, and inferred
      by decreases in N2(g)-B.E.T. specific surface area from 94 m(2)/g to 77 m(2)/g
      after 12 months, and to 66 m(2)/g after 33 months storage. Potential determining
      (H(+), OH(-)) ions loadings in the 4-11 pH range were unchanged only if the
      particles remained aggregated in NaCl but only if they were disaggregated in
      NaClO4. These differences, alongside molecular simulations and experimental ion
      loadings resolved in other studies from our group, point to important controls on
      background electrolyte ion identity on the aggregation and charge development in
      lepidocrocite. These results may apply further to other mineral surfaces of
      comparable surface (hydr)oxo populations. 

PMID- 25055063
TI  - Clinical research training.

PMID- 25055064
TI  - Spatial distribution of deaths due to Alzheimer's disease in the state of Sao
      Paulo, Brazil.
AB  - CONTEXT AND OBJECTIVE: Alzheimer's disease is a common cause of dementia and
      identifying possible spatial patterns of mortality due to this disease may enable
      preventive actions. The objective of this study was to identify spatial
      distribution patterns of mortality due to Alzheimer's disease in the state of Sao
      Paulo. DESIGN AND SETTING: Ecological and exploratory study conducted in all
      municipalities in the state of Sao Paulo. METHODS: Data on Alzheimer's disease
      mortality in the state of Sao Paulo between 2004 and 2009 were obtained from
      DATASUS (the Department of Informatics in the Brazilian Ministry of Health).
      Death rates per 100,000 inhabitants were then calculated and spatial analysis was
      performed by constructing a death rate map, global Moran index and local Moran
      index, which were used to obtain the Moran map. The kernel technique was also
      applied. The Terra View 4.0.0 software was used. RESULTS: 13,030 deaths due to
      Alzheimer were reported in the state of Sao Paulo (rate of 5.33 deaths/100,000
      inhabitants). Sao Jose do Rio Preto, Ribeirao Preto, Bauru and Aracatuba had
      higher rates. The Moran index was I = 0.085 (P < 0.002). The Moran map identified
      42 municipalities that merit intervention and the kernel estimator identified a
      high density of deaths in the northwestern region of the state. CONCLUSION:
      Higher densities of deaths due to Alzheimer were concentrated more to the north
      and northwest of the state of Sao Paulo. It was possible to identify
      municipalities that have priority for interventions to reduce the death rates due
      to this disease.

PMID- 25055065
TI  - Clinical and laboratorial features of spontaneous bacterial peritonitis in
      southern Brazil.
AB  - CONTEXT AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a severe
      complication that occurs in 8-27% of hospitalized patients with liver cirrhosis
      and ascites, with high mortality rates. This study aimed to identify the clinical
      characteristics associated with SBP. DESIGN AND SETTING: Cross-sectional study,
      conducted in a public university. METHODS: The study consecutively included
      individuals with liver cirrhosis and ascites between September 2009 and March
      2012. Forty-five patients were included: mean age 53.2 +/- 12.3 years, 82.2%
      male, 73.8% Caucasian, mean Model of End-stage Liver Disease (MELD) score of 19.5
      +/- 7.2, and 33.3% with SBP. The subjects were divided into two groups: SBP and
      controls. RESULTS: Comparison between individuals with SBP and controls showed
      that those with SBP had lower mean prothrombin activity time (36.1 +/- 16.0%
      versus 47.1 +/- 17.2%; P = 0.044) and lower median serum-ascites albumin gradient
      (SAAG) (1.2 versus 1.7, P = 0.045). There was a tendency towards higher mean MELD
      in the SBP group, not significant (22.2 +/- 7.6 versus 17.9 +/- 6.7; P = 0.067).
      There was a strong positive correlation between the neutrophil count in ascitic
      fluid and serum leukocyte count (r = 0.501; P = 0.001) and a negative correlation
      between the neutrophil count in ascitic fluid with prothrombin activity time (r =
      -0.385; P = 0.011). CONCLUSION: A few characteristics are associated with the
      presence of SBP, especially liver dysfunction, SAAG and peripheral leukocytosis.

PMID- 25055066
TI  - Continuing education on child development for primary healthcare professionals: a
      prospective before-and-after study.
AB  - CONTEXT AND OBJECTIVE: Children's developmental disorders are often identified
      late by healthcare professionals working in primary care. The aim of this study
      was to assess the impact of a continuing education program on child development,
      on the knowledge and practices of these professionals. DESIGN AND SETTING:
      Prospective single-cohort study (before-and-after study), conducted in the city
      of Belem, Para , Brazil. METHODS: Two hundred and twenty-one professionals
      working in primary healthcare (82.2%) participated in a continuing education
      program on child development and were assessed before and after implementation of
      the program through tests on their knowledge of child development, consisting of
      19 questions for physicians and 14 for nurses, and questionnaires on their
      professional practices. RESULTS: One to three years after the program, the mean
      number of correct answers in the tests had increased from 11.5 to 14.3 among
      physicians in the Healthy Family Program (Programa Familia Saudavel, PFS); 13.0
      to 14.3 among physicians in Municipal Health Units (Unidades Municipais de Saude,
      UMS); 8.3 to 10.0 among PFS nurses; and 7.8 to 9.4 among UMS nurses. In
      interviews with mothers attended by these professionals before the program, only
      21.7% reported that they were asked about their children's development, 24.7%
      reported that the professional asked about or observed their children's
      development and 11.1% received advice on how to stimulate them. After the
      program, these percentages increased to 34.5%, 54.2% and 30.3%, respectively.
      CONCLUSIONS: Professionals who participated in the program showed improved
      performance regarding child development knowledge and practices.

PMID- 25055067
TI  - Incidence of postoperative dyspepsia is not associated with prophylactic use of
      drugs.
AB  - CONTEXT AND OBJECTIVE: Preoperative fasting guidelines do not recommend H2
      receptor antagonists or proton pump inhibitors. This study investigated
      prophylactic use of gastric protection and the incidence of dyspeptic symptoms in
      the immediate postoperative period. DESIGN AND SETTING: Non-randomized
      observational investigation in a post-anesthesia care unit. METHODS: American
      Society of Anesthesiologists risk classification ASAP1 and ASAP2 patients over 18
      years of age were evaluated to identify dyspeptic symptoms during post-anesthesia
      care for up to 48 hours, after receiving or not receiving prophylactic gastric
      protection during anesthesia. History of dyspeptic symptoms and previous use of
      such medications were exclusion criteria. The odds ratio for incidence of
      dyspeptic symptoms with use of these medications was obtained. RESULTS: This
      investigation studied 188 patients: 71% women; 50.5% ASAP1 patients. Most
      patients received general anesthesia (68%). Gastric protection was widely used (n
      = 164; 87.2%), comprising omeprazole (n = 126; 76.8%) or ranitidine (n = 38;
      23.2%). Only a few patients did not receive any prophylaxis (n = 24; 12.8%).
      During the observation, 24 patients (12.8%) reported some dyspeptic symptoms but
      without any relationship with prophylaxis (relative risk, RR = 0.56; 95%
      confidence interval, CI: 0.23-1.35; P = 0.17; number needed to treat, NNT = 11).
      Omeprazole, compared with ranitidine, did not reduce the chance of having
      symptoms (RR = 0.65; 95% CI: 0.27-1.60; P = 0.26; NNT = 19). CONCLUSION: This
      study suggests that prophylactic use of proton pump inhibitors or H2 receptor
      antagonists was routine for asymptomatic patients and was not associated with
      postoperative protection against dyspeptic symptoms.

PMID- 25055069
TI  - Perineal trauma after vaginal delivery in healthy pregnant women.
AB  - CONTEXT AND OBJECTIVE: Despite all the medical care provided during delivery
      labor, perineal injury is still prevalent and may lead to diverse pelvic floor
      disorders. The aim here was to investigate the prevalence of obstetric and anal
      sphincter injuries (OASIS) in healthy pregnant women after vaginal delivery.
      DESIGN AND SETTING: Cross-sectional study involving 3,034 patients with
      singletons in a secondary hospital for low-risk cases. METHODS: A standardized
      questionnaire was prepared and applied to medical files that had been completely
      filled out (classification of the Royal College of Obstetricians and
      Gynecologists, RCOG) in order to identify OASIS and analyze risk factors
      associated with mild and severe perineal lacerations. RESULTS: The women's mean
      age was 25 years; more than half (54.4%) were primiparae. Almost 38% of the
      participants had perineal lacerations; these were severe in 0.9% of the cases.
      Previous vaginal delivery (odds ratio, OR: 1.64 [1.33-2.04]) and forceps delivery
      (OR: 2.04 [1.39-2.97]) were risk factors associated with mild perineal injuries
      (1st and 2nd OASIS classifications). Only remaining standing for prolonged
      periods during professional activity (OR: 2.85 [1.34-6.09]) was associated with
      severe perineal injuries. CONCLUSION: The prevalence of severe perineal injuries
      was concordant with data in the literature. The variable of standing position was
      considered to be a risk factor for severe perineal injury and should be further
      investigated.

PMID- 25055068
TI  - Cluster analysis to identify elderly people's profiles: a healthcare strategy
      based on frailty characteristics.
AB  - CONTEXT AND OBJECTIVES: The new social panorama resulting from aging of the
      Brazilian population is leading to significant transformations within healthcare.
      Through the cluster analysis strategy, it was sought to describe the specific
      care demands of the elderly population, using frailty components. DESIGN AND
      SETTING: Cross-sectional study based on reviewing medical records, conducted in
      the geriatric outpatient clinic, Hospital de Clinicas, Universidade Estadual de
      Campinas (Unicamp). METHODS: Ninety-eight elderly users of this clinic were
      evaluated using cluster analysis and instruments for assessing their overall
      geriatric status and frailty characteristics. RESULTS: The variables that most
      strongly influenced the formation of clusters were age, functional capacities,
      cognitive capacity, presence of comorbidities and number of medications used.
      Three main groups of elderly people could be identified: one with good cognitive
      and functional performance but with high prevalence of comorbidities (mean age
      77.9 years, cognitive impairment in 28.6% and mean of 7.4 comorbidities); a
      second with more advanced age, greater cognitive impairment and greater
      dependence (mean age 88.5 years old, cognitive impairment in 84.6% and mean of
      7.1 comorbidities); and a third younger group with poor cognitive performance and
      greater number of comorbidities but functionally independent (mean age 78.5 years
      old, cognitive impairment in 89.6% and mean of 7.4 comorbidities). CONCLUSION:
      These data characterize the profile of this population and can be used as the
      basis for developing efficient strategies aimed at diminishing functional
      dependence, poor self-rated health and impaired quality of life.

PMID- 25055070
TI  - Systemic lupus erythematosus activity and beta two microglobulin levels.
AB  - CONTEXT AND OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune
      disease with a cyclical clinical course. Evaluation of the clinical activity of
      this disease is important for choosing the correct treatment. The objective of
      this study was to analyze the value of beta-2 microglobulin (beta2M) serum levels
      in determining SLE clinical activity. DESIGN AND SETTING: Cross-sectional
      analytical study conducted at the rheumatology outpatient clinic of a private
      university hospital. METHODS: 129 SLE patients were studied regarding disease
      activity using SLEDAI (SLE Disease Activity Index) and cumulative damage using
      SLICC ACR (SLE International Collaborating Clinics/American College of
      Rheumatology Damage Index for SLE). At the same time, the beta2M serum level, ESR
      (erythrocyte sedimentation rate), anti-dsDNA (anti-double-stranded DNA) and C3
      and C4 complement fractions were determined. RESULTS: beta2M levels correlated
      positively with SLEDAI (P = 0.02) and ESR (P = 0.0009) and negatively with C3 (P
      = 0.007). Patients who were positive for anti-dsDNA had higher beta2M serum
      levels (P = 0.009). CONCLUSION: beta2M levels are elevated in SLE patients with
      active disease.

PMID- 25055071
TI  - Rational use of blood calcium determinations.
AB  - CONTEXT AND OBJECTIVE: This study was motivated by the recent excessive increase
      in requests for blood calcium determinations and laboratory tests in general, in
      the Hospital das Clinicas complex of Faculdade de Medicina, Universidade de Sao
      Paulo (HCFMUSP). Its aim was to suggest rules for the determination of total and
      ionized calcium in our intensive care units, emergency department, wards and
      outpatient services, thus contributing towards improving the quality of medical
      care and achieving more appropriate use of human and financial resources. DESIGN
      AND SETTING: Critical analysis on clinical and laboratory data and the pertinent
      scientific literature, conducted by the study group for rational clinical
      laboratory use, which is part of the Central Laboratory Division, HCFMUSP.
      METHODS: The study group reviewed scientific publications, statistics and
      clinical and laboratory data concerning requests for total and ionized calcium
      determinations in the settings of intensive care units, emergency department,
      wards and outpatient services. RESULTS: From this critical analysis, clinical
      decision flow diagrams aimed at providing guidance for ordering these tests were
      constructed. CONCLUSIONS: Use of the proposed flow diagrams may help to limit the
      numbers of inappropriate requests for ionized and total calcium determinations,
      with consequent reductions in the number of tests, risks to patients and
      unnecessary costs.

PMID- 25055072
TI  - Rare cavernous hemangioma of adrenal gland: case report.
AB  - CONTEXT: Cavernous hemangiomas of the adrenal gland are rare benign neoplastic
      tumors. The clinical presentation of adrenal hemangiomas is usually vague, and
      they are often discovered incidentally through imaging examination s performed
      for other reasons. CASE REPORT: We report the case of a non-functional adrenal
      hemangioma found incidentally in a 37-year-old man with a one-year history of
      headache and hypertension. A right adrenal mass was detected by means of magnetic
      resonance imaging. Physical examination and all laboratory values were
      unremarkable. The patient underwent laparoscopic right adrenal gland resection.
      Histopathological evaluation confirmed adrenal cavernous hemangioma. CONCLUSIONS:
      Most occurrences of cavernous hemangiomas of the adrenal gland are non-functional
      and often discovered incidentally. Although rare, these unusual benign adrenal
      masses should form part of the differential diagnosis of adrenal neoplasms. The
      proper treatment for adrenal cavernous hemangioma is surgical removal.

PMID- 25055073
TI  - Cytogenetic profile of patients with Down syndrome in southern Brazil.

PMID- 25055074
TI  - Vaccines for preventing herpes zoster in older adults.

PMID- 25055075
TI  - Neuraminidase inhibitors for preventing and treating influenza in healthy adults
      and children.

PMID- 25055076
TI  - Effect of a transtheoretical model-based stage-matched exercise intervention on
      exercise behavior and angina in patients with coronary heart disease: a
      randomized controlled trial: Retraction.

PMID- 25055078
TI  - Clinical Effects and Implications of Cardiac Rehabilitation for Implantable
      Cardioverter Defibrillator Patients: A Mixed-Methods Approach Embedding Data From
      the Copenhagen Outpatient ProgrammE-Implantable Cardioverter Defibrillator
      Randomized Clinical Trial With Qualitative Data.
AB  - BACKGROUND: The Copenhagen Outpatient ProgrammE-Implantable Cardioverter
      Defibrillator trial was a randomized clinical trial that compared a complex
      rehabilitation intervention including exercise training and psychoeducational
      interventions with usual care. A significant difference between rehabilitation
      and usual care was found in physical capacity and general and mental health.
      However, the clinical effect sizes of these findings were not investigated, and
      the findings from the quantitative and qualitative analyses were not triangulated
      to address the issue of whether the qualitative results could help explain the
      quantitative results and bring forward additional information. OBJECTIVES: The
      objectives are to (a) determine the clinical effect sizes of the primary outcomes
      and (b) triangulate the quantitative and qualitative findings. METHODS: A total
      of 196 patients with first-time implantable cardioverter defibrillator
      implantation were randomized (1:1) to comprehensive cardiac rehabilitation (12
      weeks of exercise training and 1 year of psychoeducational follow-up) versus
      treatment as usual. Two primary outcomes, perceived health (Short Form-36) and
      peak oxygen uptake, were used. Cohen d was calculated. Qualitative interviews
      were conducted with 10 patients representing the rehabilitation group.
      Triangulation was carried out by integrating the findings from the quantitative
      and qualitative results in light of each other. RESULTS: Clinically meaningful
      effects were found between groups in peak oxygen uptake, general health, and
      mental health in favor of the rehabilitation group. Within groups, we found
      medium/high effect sizes on the mental component score in the rehabilitation
      group over time and only a small effect in the usual care group. The mechanisms
      of these effects were further explained by the qualitative findings. Patients
      with better physical health learned how to interpret body signals and adjust
      exercise behavior and experienced increased physical capacity. Those with better
      mental health received support that assisted them to cope with the possibility of
      shock and death and regain trust in their bodies. CONCLUSION: The program has a
      clinical effect and is perceived as beneficial through supportive coping.

PMID- 25055079
TI  - Jiri Prochaska (1749-1820): part 1: a significant Czech anatomist, physiologist
      and neuroscientist of the eighteenth century.
AB  - Jiri (George) Prochaska (1749-1820), a Czech anatomist, physiologist, and
      neuroscientist of the eighteenth century, ranks among the major figures of Czech
      and European cultural history. The works of Jiri Prochaska, due to historical
      circumstances, were published mostly in Latin and only some in German. However,
      given that only one treatise was partially translated into English, the results
      of his extensive research activities are currently unavailable to the
      international scientific community. The achievements of Jiri Prochaska
      undoubtedly belong to the major intellectual heritage of European science and
      certainly deserve attention as such, although his research reflected the time in
      which he lived and therefore has been reevaluated by later researchers.
      Undoubtedly, it is our duty not only to remember the work and legacy of Jiri
      Prochaska, which significantly influenced the development of our knowledge, but
      also to try to critically assess his contribution in terms of today. This article
      surveys the important biographical events of Jiri Prochaska's life, taking into
      account the significance of his research. 

PMID- 25055077
TI  - Cognitive Function in Heart Failure Is Associated With Nonsomatic Symptoms of
      Depression But Not Somatic Symptoms.
AB  - BACKGROUND: Patients with heart failure (HF) have high rates of cognitive
      impairment and depressive symptoms. Depressive symptoms have been associated with
      greater cognitive impairments in HF; however, it is not known whether particular
      clusters of depressive symptoms are more detrimental to cognition than others.
      OBJECTIVE: The aim of this study was to identify whether somatic and/or
      nonsomatic depressive symptom clusters were associated with cognitive function in
      persons with HF. METHODS: Participants were 326 HF patients (40.5% women, 26.7%
      non-white race-ethnicity, aged 68.6 +/- 9.7 years). Depressive symptoms were
      measured using a depression questionnaire commonly used in medical populations:
      the Patient Health Questionnaire-9. Somatic and nonsomatic subscale scores were
      created using previous factor analytic results. A neuropsychological battery
      tested attention, executive function, and memory. Composites were created using
      averages of age-adjusted scaled scores. Regressions adjusting for demographic and
      clinical factors were conducted. RESULTS: Regressions revealed that Patient
      Health Questionnaire-9 total was associated with attention (beta = -.14, P =
      .008) and executive function (beta = -.17, P = .001). When analyzed separately,
      the nonsomatic subscale, but not the somatic symptoms subscale (P values >=
      .092), was associated with attention scores (beta = -.15, P = .004) and memory
      (beta = -.11, P = .044). Both nonsomatic (beta = -.18, P < .001) and somatic
      (beta = -.11, P = .048) symptoms were related to executive function. When
      included together, only the nonsomatic symptom cluster was associated with
      attention (beta = -.15, P = .020) and executive function (beta = -.19, P = .003).
      CONCLUSIONS: Greater overall depressive symptom severity was associated with
      poorer performance on multiple cognitive domains, an effect driven primarily by
      the nonsomatic symptoms of depression. CLINICAL IMPLICATIONS: These findings
      suggest that screening explicitly for nonsomatic depressive symptoms may be
      warranted and that the mechanisms underlying the depression-cognitive function
      relationship in HF are not solely related to sleep or appetite disturbance. Thus,
      interventions that target patients' somatic symptoms only (eg, poor appetite or
      fatigue) may not yield maximum cognitive benefit compared with a comprehensive
      treatment that targets depressed mood, anhedonia, and other nonsomatic symptoms.

PMID- 25055080
TI  - The effect of iron and fat in a diet containing green tea extract (Camellia
      sinensis) on the antioxidant capacity of some organs and the mRNA expression of
      specific genes in mice.
AB  - The hypothesis that iron and fat in the diet may affect green tea extract (GTE)
      bioactivity, in particular antioxidant capacity and gene expression, was proposed
      and tested in mice. Thirty mice were randomly assigned to have for 37 days free
      access to standard or high-fat diets with or without GTE and ferrous lactate.
      Mice were euthanized and specific organs were removed. Total antioxidant capacity
      (TAC) was measured using the ferric reducing antioxidant power (FRAP) and oxygen
      radical absorbance capacity assays. Polymerase chain reaction was performed on
      liver and heart mRNA extracts. The FRAP assay showed that GTE from the standard
      diet did not affect plasma TAC but increased TAC of heart, aorta, and duodenum.
      GTE from diets enriched with iron resulted to lower TAC of liver and heart than
      diets with GTE alone. GTE from the fatty diet did not have any effect on TAC
      compared with fatty control diet, but increased TAC in heart and aorta compared
      with standard control diet. An effect on expression of the mapk-1 and NF-kB genes
      in heart was observed in the presence of GTE. These results suggest that GTE may
      exhibit bioactivity in some organs affected by dietary fat and iron. The findings
      of this study contribute to the elucidation of the role of dietary components on
      tea bioactivity.

PMID- 25055081
TI  - Inland water microcrustacean assemblages in an altitudinal gradient in Aysen
      region (46 degrees  S, Patagonia Chile).
AB  - The Chilean Patagonia has numerous kinds of inland water ecosystems such as
      lakes, ponds, wetlands and rivers that have been poorly studied due to access
      difficulties. This study was carried out in Aysen region, in southern Chile, and
      it included different kinds of water bodies such as rivers, streams, ponds,
      lagoons and lakes distributed along an altitudinal gradient at 46 degrees  S. It
      was found a low species number, essentially cladocerans, copepods and amphipods.
      A null model was applied in order to determine the existence of regulator factors
      of species associations, and the results revealed that they are not random. The
      patterns would be influenced by geographical and limnological characteristics of
      the studied sites. Our results would agree with regional studies on habitat
      heterogeneity such as in Torres del Paine National Park and other zones in Tierra
      del Fuego island. 

PMID- 25055082
TI  - The orchid-bee faunas (Hymenoptera: Apidae) of "Reserva Ecologica Michelin",
      "RPPN Serra Bonita" and one Atlantic Forest remnant in the state of Bahia,
      Brazil, with new geographic records.
AB  - The orchid bee faunas of two private natural preserves, 'Reserva Particular do
      Patrimonio Natural da Serra Bonita' (RSB) and 'Reserva Ecologica Michelin' (REM),
      and a forest fragment inside the campus of the 'Universidade Estadual de Santa
      Cruz', were surveyed for the first time. All three areas constitute Atlantic
      Forest remnants in the southern portion of the state of Bahia, Brazil. A total of
      1,782 males belonging to 32 species were actively collected with insect nets
      during 90 hours of field work from November, 2009, to January, 2012. Euglossa
      cyanochlora Moure, 1996-one of the rarest orchid bee species-was found at RSB and
      REM, the latter representing the northernmost record for this species. Euglossa
      cognata, Moure, 1970 was found at RSB, the northernmost record for this species
      in the Atlantic Forest and the only recent record for this species at the
      northern border of Jequitinhonha river. 

PMID- 25055083
TI  - Effects of Cylindrospermopsis raciborskii strains (Woloszynska, 1912) Senayya &
      Subba Raju on the mobility of Daphnia laevis (Cladocera, Daphniidae).
AB  - Cylindrospermopsis raciborskii is a cyanobacterium distributed worldwide that is
      known to produce cyanotoxins. Some of the Brazilian strains can produce
      saxitoxins (STXs), which are classified as neurotoxins and can paralyze
      cladocerans .Daphnia laevis is a cladoceran with a wide distribution in the
      Americas and has been studied as a possible test-organism in toxicity bioassays.
      The present work tested the acute effect on D laevis mobility when fed a
      saxitoxin-producing (STX and neoSTX) C. raciborskii strain, CYRF-01, and compared
      the results with the effects of a non-toxic strain (NPCS-1). Neonates (6-24 hours
      after birth) were exposed to concentrations of C. raciborskii varying from 102 to
      106 cells.mL-1 of each strain for up to three hours. The cladocerans were then
      transferred to a medium without toxic filaments for 24 hours. Only the organisms
      exposed to the STX-producing strain showed signs of the immobilization of
      swimming movements, confirming the effects of the toxins. There was a linear
      correlation between the time required to induce stopping the swimming movement,
      with a shorter time to needed to induce immobilization at a higher the
      concentration; this correlation was inverse to the time required to recover the
      swimming movements (longer at higher concentrations, p < 0.1). D. laevis is a
      tropical and subtropical species with great potential for use in toxicity tests
      for the detection of STXs, despite being native to and found in a great array of
      freshwater bodies. This is the first assay testing STX-producing and non
      producing C. raciborskii strains on D. laevis, species that are both found in
      Brazilian ecosystems. 

PMID- 25055084
TI  - Frugivory and seed dispersal by birds in Cereus jamacaru DC. ssp. jamacaru
      (Cactaceae) in the Caatinga of Northeastern Brazil.
AB  - Studies of the dispersal modes of plants aid our understanding of the dynamics of
      resource and its availability for dispersal agents. The present work sought to
      characterize the fruiting patterns of the native Caatinga (dryland) cactus Cereus
      jamacaru, identify its principal dispersers, and evaluate the effects of seed
      passage through digestive tract of dispersers on its germination. Cereus jamacaru
      present an annual fruiting pattern and fruiting peaks occurred during June/2009
      and February/2010. A total of 135 visits by nine species of resident Caatinga
      bird species were recorded. The most frequent visiting bird species were Paroaria
      dominicana and Euphonia chlorotica. Length of bird visits varied from 15 seconds
      to 4 minutes and seeds removed by birds travelled 10.6 +/- 11.2 m until
      dispersers make the first landing perch, in some cases more than 40 meters away.
      Germination tests show birds had a high quantity of viable seeds of C. jamacaru
      in its feces. Seeds that passed through the digestive tract of birds showed a
      similar germinability of the seeds of the control group. However, the seeds
      dispersed by birds showed lowest mean germination time related to the control
      group seeds. This study highlights the potential role of birds as seed dispersers
      of C. jamacaru, swallowing the whole seeds and defecating intact seeds,
      accelerating the germination process and transporting seeds away from the mother
      plant. 

PMID- 25055085
TI  - Ecological interpretations of the leaf anatomy of amphibious species of
      Aeschynomene L. (Leguminosae - Papilionoideae).
AB  - We present the leaf anatomy of seven amphibious species of Aeschynomene L.
      (Papilionoideae, Leguminosae), interpreting their structures and ecological
      functions, and also, providing information on which their taxonomy can be based,
      especially of morphologically similar species. We evaluated Aeschynomene
      americana, A. ciliata, A. evenia, A. denticulata, A. fluminensis, A. rudis and A.
      sensitiva. The anatomy corroborates the separation of the series Americanae,
      Fluminenses, Indicae and Sensitivae, with the shape of the petiole, types of
      trichomes and quantity of vascular units in the petiole as main characteristics
      to delimit the species. The petiole shape varies from cylindric in A. americana,
      A. sensitiva and A. fluminensis, to triangular in A. evenia and quadrangular in
      A. rudis, A. denticulata and A. ciliata. We observed four types of trichomes:
      hydathode trichome, long conic trichome, short conic trichome and bulb-based
      trichome. The hydathode trichome was the most common, except for A. americana and
      A. fluminensis. Species with higher affinity with water share similar adaptive
      characteristics, including hydathode trichomes described for the first time for
      the genus. This article adds unseen descriptions for the genus and on the
      adaptation factors of the amphibious species. 

PMID- 25055086
TI  - Distribution, management and diversity of yam local varieties in Brazil: a study
      on Dioscorea alata L.
AB  - Widely spread in the tropics, yams were introduced into Brazil during the
      colonial period and are currently grown throughout the country. Despite its
      importance as a pharmacological and food source, there is a lack of studies
      describing how and where this tuber is grown in Brazil. The aim of this study was
      to provide an overview of the cultivation and distribution of Dioscorea alata in
      different Brazilian regions. A total of 63 farmers were visited in different
      municipalities and communities in four regions in the country: South, Southeast,
      Northeast and Midwest. Semi-structured interviews were conducted to collect socio
      economic, use, management and diversity data for this crop. The majority of
      interviewers were men, married, with children, using retirement benefits and
      agriculture as income and family labour as the main support in the yam
      cultivation. A wide distribution of this species was found, with the occurrence
      of D. alata in the four sampled regions. A variety of vernacular names for this
      species was collected, differing according to the region where it is cultivated.
      Most farmers cultivate yams in fields, however an increased usage of home gardens
      for the cultivation of this tuber was found. Also, most farmers cultivate yams in
      association with other crops in areas of different sizes and slash and burn
      practices, although mostly disappearing, are still being used by many farmers.
      The results of this study provide more concrete data on the distribution and
      diversity of this important crop. 

PMID- 25055087
TI  - Pollination syndromes in a Caatinga plant community in northeastern Brazil:
      seasonal availability of floral resources in different plant growth habits.
AB  - To describe plant phenological patterns and correlate functioning for the
      quantity and quality of resources available for the pollinator, it is crucial to
      understand the temporal dynamics of biological communities. In this way, the
      pollination syndromes of 46 species with different growth habits (trees, shrubs,
      herbs, and vines) were examined in an area of Caatinga vegetation, northeastern
      Brazil (7 degrees  28' 45" S and 36 degrees  54' 18" W), during two years.
      Flowering was monitored monthly in all the species, over two years (from January
      2003 to December 2004). Pollination syndromes were characterised based on floral
      traits such as size, colour, morphology, symmetry, floral resources, as well as
      on direct visual observation of floral visitors on focal plants and published
      information. We observed differences among the plant growth habits with respect
      to floral traits, types of resources offered, and floral syndromes. The flowering
      periods of the species varied among floral syndrome groups. The majority of the
      melittophilous species flowered during the rainy season in the two study years,
      while the species of the other pollination syndroms flowered at the end of the
      dry season. An asynchrony of flowering was noted among the chiropterophilous
      species, while the phalenophilous group concentrated during the rainy season. The
      overall availability of floral resources was different during the rainy and the
      dry seasons, and also it varied among plants with different growth habits. The
      availability of oil-flowers coincided with the period of low nectar availability.
      We observed a relationship between the temporal distribution of the pollination
      syndromes and the availability of floral resources among each growth habits in
      this tropical ecosystem. Resource allocation in seasonal environments, such as
      the Caatinga, can function as a strategy for maintaining pollinators,
      facilitating therefore the reproductive success of plant species. The
      availability of floral resources during all the year, specially in seasonal
      environments such as the Caatinga, may function as a strategy to maintain
      pollinator populations ensuring the reproductive success of the plants. 

PMID- 25055088
TI  - The climatic rhythm and blooms of cyanobacteria in a tropical reservoir in Sao
      Paulo, Brazil.
AB  - The present study sought to develop a methodology to analyse water quality based
      on the concepts and methods of climate and climatology. Accordingly, we attempted
      to relate hydro- and limnometeorological techniques and methodologies to a
      rhythmic analysis technique developed within the context of the Brazilian
      geographical climatology. Our goal was to assess and analyse cyanobacterial
      blooms, the main index of water quality for the reservoirs of the "Alto Tiete"
      Basin and, consequently, the Metropolitan Region of Sao Paulo, an area of high
      environmental complexity due to its high degree of development and high
      population density. The meteorological data used were collected by the Institute
      of Astronomy, Geophysics and Atmospheric Sciences at the University of Sao Paulo
      meteorological station, and the limnological data were collected through the
      Hydrological Monitoring System implemented by SABESP in the Billings and
      Guarapiranga Reservoirs and the laboratory of the same entity. The rhythmic and
      integrated analysis showed that the process of cyanobacterial blooms is dependent
      on a combination of meteorological factors as temperature and wind intensity that
      may disrupt the stability of the reservoir, providing the conditions necessary
      for the development of cyanobacteria during the stabilisation process. The pace
      of the Atlantic Polar Front Entrance during the winter in Sao Paulo is a limiting
      factor for the growth of cyanobacteria because of their high frequency, thus
      maintaining the balance of the reservoir throughout this period. The weather
      types those could cause a instability in the water column were: Cold Front
      entrance (66.67%), conflict between masses (22.22%) and the Tropical Instability
      Line (11.11%). The possibility for prevention and forecasting periods advise when
      these reservoirs should not be used, mainly with regard to recreational
      activities. 

PMID- 25055089
TI  - Aquatic insect community structure under the influence of small dams in a stream
      of the Mogi-Guacu river basin, state of Sao Paulo.
AB  - The fragmentation of lotic systems caused by construction of dams has modified
      many aquatic communities. The objective of this study was to analyse changes in
      the aquatic insect community structure by discontinuity of habitat created by
      dams along the Ribeirao das Anhumas, a sub-basin of the Mogi-Guacu River (state
      of Sao Paulo, Brazil). Entomofauna collection was carried out in 10 segments
      upstream and downstream of five dams along the longitudinal profile of the
      stream, with a quick sampling method using a D net (mesh 250 mm) with 2 minutes
      of sampling effort. The insects were sorted and identified to the lowest possible
      taxonomic level and analysed by the Shannon diversity index, beta diversity,
      richness estimated by rarefaction curves and relative participation of functional
      feeding groups. The results showed a slight reduction in diversity in the
      downstream segments, as well as along the longitudinal profile of the stream.
      However, there were no significant differences in abundance and richness between
      the upstream and downstream segments, indicating that the dams did not influence
      these variables. Differences were observed in the functional feeding groups along
      the longitudinal profile. Predator and gatherer insects were dominant in all
      segments analysed. The feeding group of shredders was more abundant in the
      segment DSIII with the participation of Marilia Muller (Odontoceridae -
      Trichoptera), although we observed a decrease of shredders and scrapers with the
      decrease of the canopy cover reducing values of beta diversity in the continuum
      of Ribeirao das Anhumas. This result demonstrated the importance of the
      conservation of the riparian vegetation in order to maintain the integrity of the
      stream. 

PMID- 25055090
TI  - Are ant assemblages of Brazilian veredas characterised by location or habitat
      type?
AB  - Wetland areas in the Brazilian Cerrado, known as "veredas", represent ecosystems
      formed on sandy soils with high concentrations of peat, and are responsible for
      the recharge of aquiferous reservoirs. They are currently under threat by various
      human activities, most notably the clearing of vegetation for Eucalyptus
      plantations. Despite their ecological importance and high conservation value,
      little is known about the actual effects of human disturbance on the animal
      community. To assess how habitat within different veredas, and plantations
      surrounding them affect ant assemblages, we selected four independent vereda
      locations, two being impacted by Eucalyptus monoculture (one younger and one
      mature plantation) and two controls, where the wetland was surrounded by cerrado
      vegetation. Ant sampling was conducted in May 2010 (dry season) using three
      complementary methods, namely baits, pitfall traps, and hand collection, in the
      wetland and in the surrounding habitats. A total of 7,575 ants were sampled,
      belonging to seven subfamilies, 32 genera and 124 species. Ant species richness
      and abundance did not differ between vereda locations, but did between the
      habitats. When impacted by the monoculture, ant species richness and abundance
      decreased in wetlands, but were less affected in the cerrado habitat. Ant species
      composition differed between the three habitats and between vereda locations.
      Eucalyptus plantations had an ant species composition defined by high dominance
      of Pheidole sp. and Solenopsis invicta, while natural habitats were defined by
      Camponotus and Crematogaster species. Atta sexdens was strictly confined to
      native habitats of non-impacted "veredas". Eucalyptus monocultures require high
      quantities of water in the early stages, which may have caused a decrease in
      groundwater level in the wetland, allowing hypogeic ants such as Labidus
      praedator to colonise this habitat. 

PMID- 25055091
TI  - Implication of anaerobic and aerobic decomposition of Eichhornia azurea (Sw.)
      Kunth. on the carbon cycling in a subtropical reservoir.
AB  - This study aimed at describing kinetic aspects of aerobic and anaerobic
      mineralization of Eicchornia azurea. The samples of aquatic macrophyte and water
      were collected in the Monjolinho Reservoir (22 degrees  00' S and 47 degrees  54'
      W). To determine the leachate potential, dried plant fragments were added to
      reservoir water, with sampling lasting for 4 months, where the particulate and
      dissolved organic carbon concentrations were measured. The kinetics of mass loss
      was obtained with 10 mineralization chambers for both aerobic and anaerobic
      conditions, with the plant fragments and reservoir water. Two additional chambers
      were used to monitor the volume of gases produced from anaerobic mineralization,
      with bioassays to determine oxygen uptake. The results were fitted to a first
      order kinetic model, from which 27.21% of detritus corresponded to labile/soluble
      fractions and 72.62% to the refractory fractions. The decay rates for the global
      mass losses of the labile/soluble components were 2.07 day-1. DOC mineralization
      was not verified for either condition. Under aerobic condition, the mass loss
      constant rate (0.0029 day-1) for the refractory fractions was 2.4 the value for
      the anaerobic one. Under anaerobic condition, the gases formation occurred in
      three phases. Based on these results, in the Monjolinho Reservoir, the
      decomposition of E. azurea that undergo within the water column and in upper
      layers of sediment is a faster process, favoring the mineralization. In contrast,
      in the lower layers of sediment the diagenetic processes (i.e. humus production
      and accumulation of organic matter) are favored. 

PMID- 25055092
TI  - Temporal change in species and functional plant traits in the moist grassland on
      the Sete Cidades National Park, Piaui, Brazil.
AB  - The present study investigated the dynamic on a short-time scale in the
      vegetation in moist grassland of the Sete Cidades National Park, Piaui. Herb
      subshrub layer samples was carried out in July 2007, 2009 and 2011. Changes in
      structural, floristic and functional traits in the community were assessed by
      species richness, diversity and similarity indices between those periods, as well
      as by hierarchical classification and ordination. Cluster and Principal Component
      Analyses identified functional groups according to 23 species trait state. To
      distinguish the contribution of space and time configuration in the community
      structure, we used the variance partition technique. The functional groups of
      chamaephytes and therophytes II were associated with wetter sites, while the
      groups of non-tussock hemicriptophytes I, tussock hemicriptophytes (FG4), and
      geophytes (FG5) were associated to the drier ones. We found a non-accelerated
      dynamics, at least on a short-time scale, represented by some descriptors in the
      community, such as the close similarity between the inventories and ordering of
      sampling transects in moist grassland. Therefore, besides considering the
      partition of the temporal niche as a mechanism for the co-existence of species,
      the heterogeneity of space dictated by environmental filters seems to determine
      the stability of the this grassland communities over time. 

PMID- 25055093
TI  - Wildlife trade in Brazil: a closer look at wild pets welfare issues.
AB  - Wild animals have been kept as pets for centuries, in Brazil companionship is one
      of the main reasons why wild species are legally bred and traded. This paper is
      an attempt to call the attention for problems concerning the welfare of wild pets
      involved in the trading system in Brazil. Some issues presented are: a) the
      significant increase in the number of wildlife breeders and traders and the
      difficulties faced by of the Brazilian government in controlling this activity;
      b) the main welfare issues faced by breeders and owners of wild pets; and c) the
      destination of wild pets no longer wanted. Finally, some recommendations are made
      having the welfare of the animals as a priority. 

PMID- 25055094
TI  - Annelida (Oligochaeta and Aphanoneura) from the Natural Reserve of Isla Martin
      Garcia (upper Rio de la Plata estuary, Argentina): biodiversity and response to
      environmental variables.
AB  - The Island of Martin Garcia--located in the Upper Rio de la Plata, to the south
      of the Uruguay River--is an outcropping of the crystalline basement. Fourteen
      sampling sites were selected, five along the littoral section of the island and
      nine in inland ponds. Four major environmental variables were measured: water
      temperature, dissolved oxygen, electrical conductivity, and pH. A total of 34
      species of Oligochaeta and Aphanoneura were found, 30 belonging to Naididae plus
      one species each of the Narapidae, Lumbricidae, Enchytraeidae, and
      Aeolosomatidae. The thirteen most frequent species were: A. leydigi (30%), N.
      bonettoi (13%), L. hoffmeisteri (11%), N. variabilis (10%), S. trivandrana
      (6.5%), A. pigueti (5.6%), D. sawayai (4.5%), D. digitata (3.5%), C. diastrophus
      (2.7%), A. costatus (2.5%), P. longiseta (2.0%), Enchytraeidae (1.5%), and A. p.
      paraguayensis (1.4%). UPGMA clustering of species based on their occurrence in
      different ecological conditions revealed two main species groups. Canonic
      correspondence analysis (CCA) was conducted with the 15 most frequent and
      abundant species in the 9 sampling sites and the 4 environmental variables.
      Results from the CCA revealed that the order of fluctuation of the environmental
      variables during the sampling period was, from the greatest to the least:
      dissolved oxygen, conductivity, pH, and water temperature. Approximately 97.6% of
      the correlations between species and environmental variables were expressed on
      axis 1 of the ordination diagram. Species richness correlated with the four
      environmental variables in the following order, from the weakest to the
      strongest: water temperature, pH, electrical conductivity, and dissolved oxygen.

PMID- 25055095
TI  - Cetacean records along a coastal-offshore gradient in the Vitoria-Trindade Chain,
      western South Atlantic Ocean.
AB  - Oceanic waters are difficult to assess, and there are many gaps in knowledge
      regarding cetacean occurrence. To fill some of these gaps, this article provides
      important cetacean records obtained in the winter of 2010 during a dedicated
      expedition to collect visual and acoustic information in the Vitoria-Trindade
      seamounts. We observed 19 groups of cetaceans along a 1300-km search trajectory,
      with six species being identified: the humpback whale (Megaptera novaeangliae, N
      = 9 groups), the fin whale (Balaenoptera physalus, N = 1), the Antarctic minke
      whale (Balaenoptera bonaerensis, N = 1), the rough-toothed dolphin (Steno
      bredanensis, N = 1), the bottlenose dolphin (Tursiops truncatus, N = 2), and the
      killer whale (Orcinus orca, N = 1). Most humpback whale groups (N = 7; 78%) were
      observed in the Vitoria-Trindade seamounts, especially the mounts close to the
      Abrolhos Bank. Only one lone humpback whale was observed near Trindade Island
      after a search effort encompassing more than 520 km. From a total of 28 acoustic
      stations, humpback whale songs were only detected near the seamounts close to the
      Abrolhos Bank, where most groups of this species were visually detected
      (including a competitive group and groups with calves). The presence of humpback
      whales at the Trindade Island and surroundings is most likely occasional, with
      few sightings and low density. Finally, we observed a significant number of
      humpback whales along the seamounts close to the Abrolhos Bank, which may
      function as a breeding habitat for this species. We also added important records
      regarding the occurrence of cetaceans in these mounts and in the Western South
      Atlantic, including the endangered fin whale. 

PMID- 25055096
TI  - Influence of fish farming in net cages on phytoplankton structure: a case study
      in a subtropical Brazilian reservoir.
AB  - This study investigated the enrichment influence due to fish farming in net cages
      on the phytoplankton composition, density and diversity in two arms of a
      subtropical reservoir (Salto Caxias, Parana). There were no statistically
      significant differences in the phytoplankton composition and diversity, as well
      as for concentrations of nutrients among the handled treatment. The density
      values were higher during the summer. Richness and Shannon diversity values were
      low during the study period. The equitability values were high during the winter
      and low in the summer. Variations of phytoplankton community and nutrients were
      mainly influenced by seasonality. The absence of significant differences between
      the treatments was probably due to the small number of net cages and fish used,
      as well as to the hydrodynamics of the studied environments, which are influenced
      by upstream rivers inflows. 

PMID- 25055097
TI  - A comparative study of resource allocation in Pteridium in different Brazilian
      ecosystems and its relationship with European studies.
AB  - Pteridium is a cosmopolitan genus that acts as an invasive species in many parts
      of the world. Most research on this genus has occurred in Europe, and there is a
      lack of data on it from South America, in spite of causing considerable
      conservation problems. We compared the biomass allocation of P. esculentum subsp.
      arachnoideum in two ecosystems in Brazil - Atlantic forest and Brazilian savanna.
      We measured the biomass of fronds, rhizomes and above-ground litter. We also
      compared the density, length and biomass of fronds from this Brazilian study with
      similar data of P. esculentum subsp. arachnoideum derived from Venezuela and P.
      aquilinum from Europe. P. esculentum subsp. arachnoideum showed a wide response
      range. We found a negative relationship between frond and necromass, indicating a
      negative feedback effect, while a positive relationship was observed between
      frond and rhizome biomass. The continental comparison of relationships showed
      that Pteridium responds in a different way in both Brazil and Europe, and that in
      Brazil fronds tend to be longer and heavier, presumably as a result of the
      continuous growing season in South America while is shortened in Europe by frost.
      The paper shows the ability of Pteridium to adapt to different ecosystems. 

PMID- 25055098
TI  - Seasonal variation of biotic and abiotic parameters in parallel neotropical
      fishponds.
AB  - The present study was carried out to evaluate the phytoplankton community and
      water quality in four parallel fishponds (FP1 to FP4) during one year. Some
      abiotic parameters of water column and phytoplankton was sampled in four sites,
      one in each fishpond. Similarity analysis showed that FP2 fishpond was markedly
      different for the others ponds with regard to phytoplankton community.
      Conductivity, orthophosphate, temperature, TSS and hardness parameters were
      significantly different (p<0.05) between fishponds and all limnological
      parameters were significantly different (p<0.01) among period (months). Organic
      matter and phosphorus of the sediment were significantly different (p<0.01) only
      among fishponds. In current study Chlorophyceae and Bacillariophyceae occurred in
      most months. Cyanobacteria density in April and May was higher in all fishponds,
      at FP3 represented 71.4% in April and FP1 represented 78.7% in May of total
      reported, with chlorophyll-a content lower than 41 mg.L-1. The physical and
      chemical parameters of fishponds water constituted relations between the
      parameters and algae occurrence. The present study however, indicated that
      Cyanobacteria was more frequent in the fishponds after the fish grow-out period
      (April), and the water quality should be monitored more frequently in this
      period, due to the high total phosphorus, orthophosphate and chlorophyll-a
      contents. 

PMID- 25055099
TI  - Implications of water hardness in ecotoxicological assessments for water quality
      regulatory purposes: a case study with the aquatic snail Biomphalaria glabrata
      (Say, 1818).
AB  - Water hardness is a property depending on the presence of alkaline earth metals,
      mainly calcium and magnesium. Among the strategies for water quality monitoring,
      ecotoxicological assays are performed to minimize impacts and classify water
      bodies. For these laboratory evaluations parameters are previously defined in the
      guidelines, including water hardness for both cultivation and testing medium. The
      present work was performed to evaluate the effects of different levels of water
      hardness on the survival and reproduction of the freshwater snail Biomphalaria
      glabrata and discuss the influence of natural water hardness on the results of
      ecotoxicological tests with these environmental samples. Comparing the groups it
      was possible to observe that those maintained in waters with least hardness had
      lower reproductive success, while the groups maintained in highest hardness
      showed better reproduction. These data show that waters with low hardness make
      the reproduction of the snail B. glabrata unfeasible, and this reveal a problem
      for ecotoxicity assays using natural water samples. 

PMID- 25055100
TI  - Structure of the testate amoebae community in different habitats in a neotropical
      floodplain.
AB  - This study evaluated the differences in composition, abundance and morphology of
      testate amoebae among different habitats of the same aquatic environment
      (plankton, aquatic macrophyte and sediment) in the Upper Parana River floodplain.
      Triplicate samplings were undertaken monthly at each habitat from April 2007 to
      March 2008. The structure of the community of testate amoebae was different among
      the habitats. The species typical for each habitat, according to Indval, were
      classified by their shell morphology. Arcella species together with Difflugia
      gramen and Difflugia pseudogramem were more abundant for plankton. Trinema and
      Phryganella stood out by their abundance and frequency in aquatic macrophytes.
      Centropyxis was an indicator of sediment. The results indicated a higher
      frequency of hemispherical and spherical shells in plankton and spherical and
      elongated shells in aquatic macrophytes. In the sediment, there was a high
      frequency of elongated species. Our results support the hypothesis that the
      community of testate amoebae has different structures among the habitats,
      refuting the idea that the organization of this community in plankton is guided
      by random events like the resuspension of organisms from the sediment and their
      displacement from marginal vegetation. 

PMID- 25055101
TI  - New record of Akashiwo sanguinea (Dinophyta) in the tropical estuarine waters of
      Northeastern Brazil (Western Atlantic).
AB  - This study reports the occurrence and the effect of the environmental factors on
      the spatial and temporal distribution of the dinoflagellate Akashiwo sanguinea
      (Hirasaka) Hansen & Moestrup in estuarine waters of northeastern Brazil. Samples
      were collected at seven stations from March 2007 to February 2008 during high
      tide and low tide, using Van Dorn bottles. The samples were immediately fixed
      with Lugol and analyzed with the Utermohl method. Water samples were also
      collected for the identification of the hydrological characteristics of the area.
      Akashiwo sanguinea occurred throughout the annual cycle and at all sampling sites
      with densities ranging between 5 and 410 x 103 cells.L-1. The highest densities
      were recorded at low tide, especially during the months of the rainy season
      (July: 210 x 103 cells.L-1; August: 410 x 103 cells.L-1). Density values were
      within the normal range and blooms were not detected. Despite being common in the
      area, the species showed preference for sites with high concentrations of
      orthophosphate and total dissolved phosphorus and with salinity in the mesohaline
      regime. 

PMID- 25055102
TI  - Diet and helminths of Enyalius brasiliensis (Lacertilia, Iguania, Leiosauridae)
      in an Atlantic Rainforest remnant in southeastern Brazil.
AB  - Our study aimed to add information about the diet and endoparasites of Enyalius
      brasiliensis from an Atlantic Rainforest remnant in the state of Rio de Janeiro,
      southeastern Brazil. Regarding diet, E. brasiliensis consumed arthropods, with
      caterpillars and beetles being the most important preys. Regarding helminth
      parasites, overall prevalence was low (9.5%), with 238 nematodes of the genus
      Physaloptera found in the stomach of one specimen and one nematode of the genus
      Rhabdias inside the lung of another. Our results corroborate the observations of
      previous studies that indicate that lizards of the genus Enyalius tend to feed
      mainly on relatively large-bodied arthropods and to harbour depauperate
      endoparasite fauna. 

PMID- 25055103
TI  - Biological aspects of Tiracola grandirena (Herrich-Schaffer, 1868) (Lepidoptera:
      Noctuidae): a polyphagous armyworm.
AB  - We studied the biology of Tiracola grandirena (Herrich-Schaffer, 1868)
      (Lepidoptera: Noctuidae: Hadeninae) at 25 +/- 1  degrees C, 70 +/- 10% RH and 14
      hours of photo phase. Three experiments, using 150 larvae each, were conducted
      for the larval stage. In the first, used to assess the duration and survival of
      all stages, insects were reared individually and fed an artificial diet (Grenee).
      In the second, individuals were also reared separately, but were fed leaves of 10
      plants from different families. In the third, the larvae were not individualised,
      the food plants were rotated such as to provide three plant species every 48
      hours. In the first experiment, the viability of the eggs, larvae, pupae and
      prepupae was 91.9, 94.7, 32.49 and 43.5%, respectively. The average duration of
      the egg, larvae, prepupae, pupae and adult were 6.0, 25.3, 25.7, 21.4 and 12.7
      days, respectively. The prolonged prepupal period indicates that T. grandirena
      can develop larval (prepupal) diapause. The results of the experiments with
      different host plants showed that T. grandirena is polyphagous at species,
      population and individual level. 

PMID- 25055104
TI  - Cytogenetics analyses among populations of the fish Iheringichtys labrosus
      (Kroyer, 1874) (Siluriformes, Pimelodidae). Karyotype analysis, C- banding and
      AgRONs distribution.
AB  - Karyotypic data on Iheringichthys labrosus from several populations of Parana
      River/Argentina are presented. The diploid number was 2n=56 and the karyotype
      consisted of 42m/sm + 14st/a (NF= 98). The AgNORs were observed in telomeres of
      the long arm of a st/a chromosome pair. These sites were also positive after C
      banding. Heterochromatin was observed in the telomeric position in some
      chromosomal pairs and can be found in one or both metacentric chromosome arms.
      The obtained results were compared with those reported for different populations
      from Brazilian rivers and the similarity among them was evident. However,
      discordant chromosome formulae and karyotype features between samples should be
      carefully taken because, in some cases, they seem to be more technical artifacts
      than real differences. 

PMID- 25055105
TI  - Baseline micronuclei and nuclear abnormalities frequencies in native fishes from
      the Parana River (Argentina).
AB  - This work aims to establish baseline frequencies of micronuclei (MN) and nuclear
      abnormalities (NA) in native fish species collected in situ from the Parana
      River. For this purpose, the micronucleus test was applied in peripheral blood
      erythrocytes from specimens obtained from samplings collected at two localities
      (Posadas and Candelaria, Misiones, Argentina) during the period 2007-2010. The
      results were statistically analyzed using the Kruskal Wallis test. Data from nine
      fish species were obtained, among which Steindachnerina brevipinna
      (Characiformes) revealed the highest baseline frequency of MN and NA, showing
      statistically significant differences with regard to the other analyzed species.
      These results are the first report of baseline MN and NA frequencies for native
      fish species studied and could be useful for future comparisons with data of
      fishes belonging to other environments. 

PMID- 25055106
TI  - Non-destructive equations to estimate the leaf area of Styrax pohlii and Styrax
      ferrugineus.
AB  - We developed linear equations to predict the leaf area (LA) of the species Styrax
      pohlii and Styrax ferrugineus using the width (W) and length (L) leaf dimensions.
      For both species the linear regression (Y=alpha+bX) using LA as a dependent
      variable vs. W * L as an independent variable was more efficient than linear
      regressions using L, W, L2 and W2 as independent variables. Therefore, the LA of
      S. pohlii can be estimated with the equation LA=0.582+0.683WL, while the LA of S.
      ferrugineus follows the equation LA=-0.666+0.704WL. 

PMID- 25055107
TI  - Yield per recruit of the peacock bass Cichla monoculus (Spix and Agassiz, 1831)
      caught in Lago Grande at Manacapuru (Amazonas - Brazil).
AB  - We evaluated the stock of peacock bass Cichla monoculus caught by a small-scale
      fishing fleet in Lago Grande at Manacapuru. The database was constructed by
      monthly samplings of 200 fish between February 2007 and January 2008. We measured
      the total length (cm) and total weight (gr) of each fish. We employed previously
      estimated growth parameters to run a yield per recruit model and analyse
      scenarios changing the values of the age of the first catch (Tc), natural
      mortality (M), and fishing mortality (F). Our model indicated an occurrence of
      overfishing because the fishing effort applied to catch peacock in Lago Grande at
      Manacapuru is greater than that associated with the maximum sustainable yield. In
      addition, the actual size of the first catch is almost half of the estimated
      value. Although there are difficulties in enforcing a minimum size of the catch,
      our results show that an increase in the size of the first catch to at least 25
      cm would be a good strategy for management of this fishery. 

PMID- 25055108
TI  - Sex ratio and parental investment in Trypoxylon (Trypargilum) agamemnon Richards
      (Hymenoptera, Crabronidae).
AB  - The life history and sex ratio data of the solitary wasp Trypoxylon agamemnon
      nesting in trap-nests in southern Brazil was recorded from January 2002 to
      December 2007. Its sex ratio is strongly female-biased, being bivoltine or
      multivoltine with until three generations per year. It has two alternative life
      histories (diapause and direct development) and overlapping generations. In
      addition to the conflict of interest between the sexes, it is possible that local
      mate competition occurs between males and may cause a greater investment in the
      production of females. 

PMID- 25055109
TI  - Proposed method for agglutinating antibody titer analysis and its use as
      indicator of acquired immunity in pacu, Piaractus mesopotamicus.
AB  - Antibody can be assessed by agglutinating antibody titer which is a quantitative
      measure of circulating antibodies in serum from fish previously immunized. The
      antibody evaluation has been performed with different fish species, and is
      considered a reliable method that can be applied to confirm several hypothesis
      regarding acquired immunity, even in conjunction with precise methods to describe
      immune mechanisms. In order to provide appropriate analytical methods for future
      studies on the specific immune system of native fish, the present study
      standardized on assay to measure the serum agglutinating antibody titer produced
      after immunization with inactivated A. hydrophila and levamisole administration
      in pacu. It was possible to determine the agglutinating antibodies titer in a
      satisfactorily way in pacu immunized with inactive A. hydrophila, and the highest
      titers were observed on fish fed with levamisole. 

PMID- 25055110
TI  - Evaluation of hollocelulase production by Lentinula edodes (Berk.) Pegler during
      the submerged fermentation growth using RSM.
AB  - The cellulase proteins have a great importance in the enzymatic hydrolysis of
      woody biomass. Despite of costs being a major concern, it has been a stimulus to
      study basidiomycetes biochemical properties which degrade lignocellulosic
      material and have prompted the processes' study for obtaining cellulolytic
      enzymes in fungi. The objective of this research was to evaluate the effects of
      the initial nitrogen content on (ammonium sulfate) and on sugar cane bagasse,
      which hereby, acts as an inducer of hydrolytic enzymes to produce cellulases and
      xylanases, using three Lentinula edodes (Berk.) Pegler strains as a
      transformation agent. A factorial design with 22 replications in the central
      point was conducted, varying concentrations of ammonium sulfate and sugar cane
      bagasse. The submerged cultures carried out in synthetic culture medium and
      incubated at 25 degrees C for 7 days on an orbital shaker at 150 rpm. The total
      protein and cellulase activity as endoglucanase, exoglucanase and beta
      glucosidase and the xylanase was also determined. The results showed that the
      production of hydrolytic enzymes was stimulated by the presence of high
      concentrations of sugar cane bagasse (30g/L), characterizing it as an inducer due
      to the demonstrated proportional relationship. Thus, ammonium sulfate acted as a
      reducing agent in the synthesis of enzymes, being the low concentrations (0.1g/L)
      indicated for the enzyme production system under study. Among the studied
      strains, the EF52 showed higher activity for xylanase, endoglucanases, beta
      glucosidase and also protein. 

PMID- 25055111
TI  - Description of Karyotype of Kerodon acrobata, an endemic rodent in Brazilian
      Cerrado.
AB  - Kerodon acrobata is a caviidae rodent endemic from Brazilian Cerrado. It was
      described only in 1997 and the data about it is very scarce. The aim of this work
      was to characterize the karyotype of K. acrobata. Giemsa staining, nucleolar
      organizer region (NOR) banding, C-positive heterochromatin banding and DAPI
      fluorescence were used in N metaphases of a specimen collected in Asa Branca
      Farm, in Aurora do Tocantins municipality, Tocantins state, Brazil. K. acrobata
      showed the same diploid number, fundamental number and chromosome morphology as
      Kerodon rupestris. But its NOR location and heterochromatin distribution patterns
      indicated a unique cytogenetic profile when compared to its sister species,
      emphasizing the evolutionary uniqueness of this relatively new and unknown
      species. This record also extends the distribution of this species northward. 

PMID- 25055112
TI  - New records of amphoroid diatoms (Bacillariophyceae) from Cachoeira River,
      Northeast Brazil.
AB  - Amphoroid taxa have been revised in recent decades. Many species formerly
      assigned to Amphora have been transferred to other recently proposed genera, as
      Seminavis (Naviculaceae) and Halamphora (Catenulaceae). In Brazil, there are few
      studies focused on amphoroid taxonomy. This study presents a taxonomic
      investigation of five uncommon amphoroid taxa from Brazilian diatom flora:
      Seminavis pusilla, S. strigosa, Amphora ectorii, Halamphora ghanensis and
      Halamphora sp. Seminavis strigosa is identical in valve morphology and
      morphometrical data to Amphora twenteana, and its synonymy is proposed. Seminavis
      pusilla, poorly found in Brazilian waters, has expanded its distribution.
      Halamphora ghanensis is a new record to American continent while Amphora ectorii
      are new to Brazilian aquatic systems. Halamphora sp. has distinct ultrastructural
      features in relation to similar species and is probably new for science. 

PMID- 25055113
TI  - First report of Phanerotoma bennetti Muesebeck (Hymenoptera, Braconidae,
      Cheloninae) parasitizing Hypsipyla grandella (Zeller) and Hypsipyla ferrealis
      Hampson (Lepidoptera, Pyralidae) in crabwood in Brazil.

PMID- 25055115
TI  - Barnacle larvae exploring surfaces with variable hydrophilicity: influence of
      morphology and adhesion of "footprint" proteins by AFM.
AB  - Interaction forces of adhesive proteins employed by cyprid larvae of Amphibalanus
      amphitrite for temporary attachment during surface exploration in marine fouling
      were studied by AFM force spectroscopy using chemically modified, reactive
      colloidal probes. The proteins were covalently attached to the surfaces of the
      probes by incubation in the protein deposits (footprints) left behind at the
      surface by the cyprids. This covalent coupling enabled robust and reproducible
      probing of adhesion of the attachment proteins to model surfaces with variable
      hydrophilicity. Three model monolayer surfaces were designed and prepared that
      exhibited different wettabilities derived from variations in the monolayer
      chemical composition. The morphology and size of cyprid protein deposits was
      imaged by AFM. The deposits showed larger area of spreading on more hydrophobic
      surfaces, whereas the overall volume of the secreted proteins exhibited no
      significant variation. Notable difference in adhesion forces was found among the
      surfaces by force spectroscopy, with substantially higher values measured on the
      hydrophobic surface (21 +/- 2 nN) than that measured on the more hydrophilic
      surface (7.2 +/- 1 nN). The same surfaces were also tested in laboratory essays.
      Rather surprisingly, no significant differences were found in values of
      fractional cyprid settlement among the surfaces studied, indicating that
      variations of surface wettability and adhesion strength of settlement proteins
      may be insufficient to explain settlement trends. 

PMID- 25055116
TI  - Repetitive thought dimensions, psychological well-being, and perceived growth in
      older adults: a multilevel, prospective study.
AB  - BACKGROUND AND OBJECTIVES: Forms of repetitive thought (RT) such as worry are
      clearly related to states such as anxiety and depression. However, the presence
      of other forms such as reminiscing suggests that RT could also relate to
      eudaimonic well-being (EWB). Furthermore, a largely overlooked characteristic,
      total tendency to engage in RT, may associate with a particular kind of EWB,
      namely, perceived growth (PG). DESIGN: Older adults (N=150) were interviewed semi
      annually for up to 10 waves. METHODS: Participants completed a battery of RT
      measures at baseline and annual assessments of psychological well-being (PWB) and
      PG. Multilevel models tested the prospective, between-person relationships
      between baseline RT and future PWB and PG. RESULTS: RT qualities prospectively
      predicted both PWB and PG: more positive valence best predicted PWB whereas more
      negative valence and more total RT best predicted PG. Furthermore, RT qualities
      largely accounted for a negative between-person relationship between PWB and PG.
      CONCLUSIONS: Different qualities of RT promoted different kinds of EWB, and a
      negative association between different kinds of EWB could be attributed to their
      different RT antecedents.

PMID- 25055117
TI  - Targeting MET Amplification as a New Oncogenic Driver.
AB  - Certain genetically defined cancers are dependent on a single overactive oncogene
      for their proliferation and survival, a phenomenon known as "oncogene addiction".
      A new generation of drugs that selectively target such "driver oncogenes"
      manifests a clinical efficacy greater than that of conventional chemotherapy in
      appropriate genetically defined patients. MET is a proto-oncogene that encodes a
      receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a
      subset of advanced cancers as result of various genetic alterations including
      gene amplification, polysomy, and gene mutation. Our preclinical studies have
      shown that inhibition of MET signaling either with the small-molecule MET
      inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in
      marked antitumor effects in cancer cell lines with MET amplification both in
      vitro and in vivo. Furthermore, patients with non-small cell lung cancer or
      gastric cancer positive for MET amplification have shown a pronounced clinical
      response to crizotinib. Accumulating preclinical and clinical evidence thus
      suggests that MET amplification is an "oncogenic driver" and therefore a valid
      target for treatment. However, the prevalence of MET amplification has not been
      fully determined, possibly in part because of the difficulty in evaluating gene
      amplification. In this review, we provide a rationale for targeting this genetic
      alteration in cancer therapy. 

PMID- 25055118
TI  - The chronic lymphocytic leukemia clone disrupts the bone marrow microenvironment.
AB  - The systematic localization of chronic lymphocytic leukemia (CLL) B-cells in the
      bone marrow (BM), together with the ex vivo protective effect of stromal cells on
      their spontaneous apoptosis, both indicate a specific role of the BM
      microenvironment. In vivo, the impact of CLL cells on mesenchymal stromal cells
      (MSCs) remains a source of debate. Here, we quantified and expanded colony
      forming unit-fibroblasts (CFU-Fs) from CLL-BM under standard conditions, analyzed
      the expression of selected genes, and studied secretion profiles. We observed
      failing of CLL-BM cultures in standard conditions (45.5% vs. <0.1%), and even
      after adding basic fibroblast growth factor (bFGF), there were fewer CFU-F than
      from normal BM (1.3 vs. 40/10(6) cells respectively; P<0.01). Furthermore, their
      polygonal aspect and low proliferative capacity, together with the expression of
      384 selected genes and a secreted set of molecules related to senescence
      associated secretory phenotype indicated a state of senescence, further confirmed
      by the higher proportion of senescence-associated beta-galactosidase (SA-betaGAL)
      positive cells and p16INK4a overexpression. In our hands, hypoxic conditions (5%
      O2) did not rescue CFU-Fs. Given the role of MSC in BM tissue organization, we
      studied hematons that are generally considered to be elementary BM units. These
      structures were rare or had even disappeared completely. When hematons were
      present, we systematically observed nodular B-CLL cell invasion only. These data
      confirm that the B-CLL clone has a marked impact on MSC and disrupts BM
      organization in vivo, raising new questions about in vivo pathophysiology. 

PMID- 25055119
TI  - How can we identify and communicate the ecological value of deep-sea ecosystem
      services?
AB  - Submarine canyons are considered biodiversity hotspots which have been identified
      for their important roles in connecting the deep sea with shallower waters. To
      date, a huge gap exists between the high importance that scientists associate
      with deep-sea ecosystem services and the communication of this knowledge to
      decision makers and to the wider public, who remain largely ignorant of the
      importance of these services. The connectivity and complexity of marine
      ecosystems makes knowledge transfer very challenging, and new communication tools
      are necessary to increase understanding of ecological values beyond the science
      community. We show how the Ecosystem Principles Approach, a method that explains
      the importance of ocean processes via easily understandable ecological
      principles, might overcome this challenge for deep-sea ecosystem services.
      Scientists were asked to help develop a list of clear and concise ecosystem
      principles for the functioning of submarine canyons through a Delphi process to
      facilitate future transfers of ecological knowledge. These ecosystem principles
      describe ecosystem processes, link such processes to ecosystem services, and
      provide spatial and temporal information on the connectivity between deep and
      shallow waters. They also elucidate unique characteristics of submarine canyons.
      Our Ecosystem Principles Approach was successful in integrating ecological
      information into the ecosystem services assessment process. It therefore has a
      high potential to be the next step towards a wider implementation of ecological
      values in marine planning. We believe that successful communication of ecological
      knowledge is the key to a wider public support for ocean conservation, and that
      this endeavour has to be driven by scientists in their own interest as major deep
      sea stakeholders. 

PMID- 25055120
TI  - [3 + 3]-cycloaddition reactions of alpha-acidic isocyanides with 1,3-dipolar
      azomethine imines.
AB  - alpha-Acidic isocyanides are versatile reagents in organic synthesis, especially
      for the synthesis of five-membered heterocycles via [3 + 2]-cycloaddition
      reactions with activated multiple bonds. In this communication, the first [3 + 3]
      cross-cycloaddition of alpha-acidic isocyanides with 1,3-dipolar azomethine
      imines to generate a series of 1,2,4-triazine derivatives with significant
      regiochemical control under mild catalytic reaction conditions is described. This
      new strategy shows that alpha-acidic isocyanides can also be taken as potent
      reagents for the synthesis of six-membered heterocycles through [3 + 3]-cross
      cycloaddition reactions with 1,3-dipoles. 

PMID- 25055121
TI  - Genomic landscape of glioblastoma and the potential clinical utility.

PMID- 25055122
TI  - Can miRNA-based real-time PCR be used to classify medulloblastomas?

PMID- 25055123
TI  - PDK1: a new therapeutic target for glioblastoma?

PMID- 25055127
TI  - Magnetic resonance spectroscopy and beyond for pediatric brain tumors.

PMID- 25055124
TI  - Measuring the pons: a non-invasive biomarker for pediatric diffuse intrinsic
      pontine glioma.

PMID- 25055128
TI  - Postoperative stereotactic radiosurgery for resected brain metastasis.
AB  - Despite therapeutic advances in management, the prognosis of patients with brain
      metastasis remains dismal. Treatment options include surgical resection, whole
      brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). Patients who
      undergo surgical resection typically receive WBRT as adjuvant therapy. However,
      several studies have demonstrated an association between WBRT and neurotoxicity.
      Thus, clinicians are increasingly delaying WBRT in favor of postoperative use of
      SRS. In this review, we will discuss the current literature exploring the
      efficacy and toxicity of postoperative SRS in the treatment of patients with
      resected brain metastasis.

PMID- 25055129
TI  - The diagnosis and treatment of brain metastases in EGFR mutant lung cancer.
AB  - The epidemiology of non-small-cell lung cancer (NSCLC) has changed with a new
      pattern of disease emerging - a form of adenocarcinoma in mostly younger female
      patients, who are never or light smokers and more frequently in East Asian
      populations. Description of EGF receptor (EGFR) mutations has allowed new
      management strategies to evolve. Oral targeted therapies have broadened the
      treatment options in the advanced setting with the potential for periods of long
      term response. The brain is a common site of metastases with EGFR mutated lung
      cancer typically displaying asymptomatic, small volume, multiple lesions that
      respond to treatment. We explore the role of local and system therapies for brain
      metastases in this disease including the role of EGFR inhibitors.

PMID- 25055130
TI  - Prophylactic cranial irradiation: recent outcomes and innovations.
AB  - Brain metastases represent a frequent problem in several malignancies. They can
      shorten survival while causing significant morbidity and impairment in the
      patient's quality of life. Prophylactic cranial irradiation (PCI) has become an
      integral part of the standard of care in small cell lung cancer (SCLC), yet its
      role in other malignancies remains the subject of significant discussion. Its
      role has been extensively investigated in non-small cell lung cancer and less so
      for breast cancer and other malignancies. Improvements in medical care as well as
      in whole brain radiotherapy (WBRT) techniques may improve the risk-benefit ratio
      of this therapy so as to expand its role in cancer care. The use of memantine in
      WBRT patients as well as the use of hippocampal avoidance techniques are of
      particular interest in this effort. Herein, we review the history of PCI, its
      current use, and areas of investigation in the application of PCI.

PMID- 25055131
TI  - Treating glioblastoma patients with poor performance status: where do we go from
      here?
AB  - Approximately one third of all glioblastoma patients exhibit an impaired
      functional status in the perioperative setting. Their optimal management is
      difficult to define. The only available prospective study in poor performance
      status (PS) patients has been performed in elderly patients (>= 70 years). In
      this population, treatment with temozolomide was shown to be safe and to be
      associated with a clinically significant improvement of PS in one third of
      patients. In young patients (<70 years), daily clinical experience and
      retrospective data show that some patients can benefit from temozolomide
      radiochemotherapy, abbreviated radiation courses, upfront chemotherapy or early
      use of bevacizumab. However, prospective studies are needed to correctly evaluate
      these strategies, namely their impact on functional status and quality of life.

PMID- 25055132
TI  - Rapid weight loss alters muscular performance and perceived exertion as well as
      postural control in elite wrestlers.
AB  - AIM: The aim was to assess the effects of rapid decline of body mass on postural
      control, muscular performance and rating perceived exertion in elite free style
      wrestlers. METHODS: Ten high-level wrestlers (age: 19.3 +/- 2.5 years, height:
      175.7 +/- 4.9 cm, body mass before dieting: 77.16 +/- 11.94 kg) are included in
      the present study. Diet was monitored for all the athletes. Athropometric
      measurements and a variety of functional tests such as isometric hand grip
      strength (IHG) and isometric back strength (IBS) with dynamometers, dynamic
      postural control (DPC) with star excursion balance test, and rating of perceived
      exertion (RPE) to a standard exercise of knee pushups, were performed before and
      after diet completion. RESULTS: The diet was based on food restriction and
      dehydration. Body mass, lean body mass and body water significantly decreased
      (P<0.001; P<0.004, P<0.001 respectively). There was no significant decrease in
      fat mass (P<0.061). Furthermore, IHG and IBS significantly decreased (P<0.001).
      DPC significantly altered with the left supporting leg in two positions of the
      right leg (posteromedial, P<0.038; posterior, P<0.012). At last, RPE
      significantly increased (P<0.001). CONCLUSION: Previous studies showed that the
      rapid decline of body mass affects health and muscular and energetic performance
      while the present study highlights that it also alters perceived exertion and
      dynamic postural control.

PMID- 25055133
TI  - A new approach to the analysis of antibiotic resistance data from hospitals.
AB  - We aimed to develop a new approach to the analysis of antimicrobial resistance
      data from the hospitals, which allows simultaneous analysis of both individual-
      and population-level determinants of bacterial resistance. This was a
      retrospective cohort study that included adult patients who stayed in the
      hospital >2 days. We analyzed data using shared frailty Cox models and tested our
      approach using a priori hypotheses based on biology and epidemiology of
      antibiotic resistance. For gram-negative bacteria, the use of the major selecting
      antibiotic by an individual was the main risk factor for acquiring resistant
      species. Hazard ratios (HRs) were strikingly high for ceftazidime-resistant
      Enterobacter species (HR=11.17; 95% confidence interval [CI]: 5.67-22.02),
      ciprofloxacin-resistant Pseudomonas aeruginosa (HR=4.41; 95% CI: 2.14-9.08), and
      imipenem-resistant P. aeruginosa (HR=7.92; 95% CI: 4.35-14.43). Ward-level use
      was significant for vancomycin-resistant enterococci (VRE) (HR=1.40; 95% CI: 1.07
      1.83) and for imipenem-resistant P. aeruginosa (HR=1.40; 95% CI: 1.08-1.83).
      Previous incidence of infection in the same ward increased the risk of acquiring
      methicillin-resistant Staphylococcus aureus (HR=1.22; 95% CI: 1.15-1.30) and VRE
      (HR=1.53; 95% CI: 1.38-1.70). Our results were consistent with our hypotheses and
      showed that combining population- and individual-level data is crucial for the
      exploration of antimicrobial resistance development. 

PMID- 25055135
TI  - The specificity of Av3 sea anemone toxin for arthropods is determined at linker
      DI/SS2-S6 in the pore module of target sodium channels.
AB  - Av3 is a peptide neurotoxin from the sea anemone Anemonia viridis that shows
      specificity for arthropod voltage-gated sodium channels (Navs). Interestingly,
      Av3 competes with a scorpion alpha-toxin on binding to insect Navs and similarly
      inhibits the inactivation process, and thus has been classified as 'receptor site
      3 toxin', although the two peptides are structurally unrelated. This raises
      questions as to commonalities and differences in the way both toxins interact
      with Navs. Recently, site-3 was partly resolved for scorpion alpha-toxins
      highlighting S1-S2 and S3-S4 external linkers at the DIV voltage-sensor module
      and the juxtaposed external linkers at the DI pore module. To uncover channel
      determinants involved in Av3 specificity for arthropods, the toxin was examined
      on channel chimaeras constructed with the external linkers of the mammalian brain
      Nav1.2a, which is insensitive to Av3, in the background of the Drosophila DmNav1.
      This approach highlighted the role of linker DI/SS2-S6, adjacent to the channel
      pore, in determining Av3 specificity. Point mutagenesis at DI/SS2-S6 accompanied
      by functional assays highlighted Trp404 and His405 as a putative point of Av3
      interaction with DmNav1. His405 conservation in arthropod Navs compared with
      tyrosine in vertebrate Navs may represent an ancient substitution that explains
      the contemporary selectivity of Av3. Trp404 and His405 localization near the
      membrane surface and the hydrophobic bioactive surface of Av3 suggest that the
      toxin possibly binds at a cleft by DI/S6. A partial overlap in receptor site-3 of
      both toxins nearby DI/S6 may explain their binding competition capabilities. 

PMID- 25055136
TI  - Potential protective effect of L-cysteine against the toxicity of acrylamide and
      furan in exposed Xenopus laevis embryos: an interaction study.
AB  - The embryo toxicities of two food-processing-induced toxic compounds, acrylamide
      and furan, with and without added L-cysteine were examined individually and in
      mixtures using the frog embryo teratogenesis assay-Xenopus (FETAX). The following
      measures of developmental toxicity were used: (a) 96 h LC50, the median
      concentration causing 50% embryo lethality; (b) 96 h EC50, the median
      concentration causing 50% malformations of the surviving embryos; and (c)
      teratogenic index (96 h LC50/96 h EC50), an estimate of teratogenic risk.
      Calculations of toxic units (TU) were used to assess possible antagonism,
      synergism, or response addition of several mixtures. The evaluated compounds
      demonstrated counterintuitive effects. Furan had lower than expected toxicity in
      Xenopus embryos and, unlike acrylamide, does not seem to be teratogenic. However,
      the short duration of the tests may not show the full effects of furan if it is
      truly primarily genotoxic and carcinogenic. L-Cysteine showed unexpected
      properties in the delay of hatching of the embryos. The results from the
      interaction studies between combination of two or three components (acrylamide
      plus L-cysteine; furan plus L-cysteine; acrylamide plus furan; acrylamide plus
      furan and L-cysteine) show that furan and acrylamide seem to have less than
      response addition at 1:1 toxic unit ratio in lethality. Acrylamide and L-cysteine
      show severe antagonism even at low 19 acrylamide/1 L-cysteine TU ratios. Data
      from the mixture of acrylamide, furan, and L-cysteine show a slight antagonism,
      less than would have been expected from binary mixture exposures. Bioalkylation
      mechanisms and their prevention are discussed. There is a need to study the
      toxicological properties of mixtures of acrylamide and furan concurrently formed
      in heat-processed food.

PMID- 25055137
TI  - High frequency and clinical prognostic value of MYD88 L265P mutation in primary
      cutaneous diffuse large B-cell lymphoma, leg-type.
AB  - IMPORTANCE: The activating mutation of MYD88 L265P is a frequent feature of
      primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT), reported
      in up to 69% of the cases. Whether patients with MYD88 mutation display specific
      clinical and evolutive features has not been evaluated. OBJECTIVE: To identify
      the clinical characteristics associated with MYD88 mutation, confirm its high
      prevalence, and evaluate its effect on prognosis in patients with PCLBCL-LT.
      DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter study was
      conducted using the medical records of patients from dermatology departments
      belonging to the French Study Group for Cutaneous Lymphomas. Sixty-one patients
      with a diagnosis of PCLBCL-LT made between 1988 and 2010 who were available for
      molecular study were included. Of these, 58 patients displaying interpretable
      results constituted the study group. Median follow-up was 33 months, and 39
      patients (67%) were monitored until death. MAIN OUTCOMES AND MEASURES: Clinical
      features (age, sex, number of skin lesions, tumor stage, and location as leg vs
      elsewhere), MYD88 mutation (allele-specific TaqMan polymerase chain reaction
      assay), treatment regimen, and outcome were recorded. Baseline characteristics
      and outcome were compared according to the status of MYD88. RESULTS: The median
      age of the patients was 79 years, and 59% were female. Skin lesions were located
      on the leg in 76% of the cases. Thirty-four of 58 patients (59%) harbored the
      MYD88 L265P mutation. Patients had similar clinical characteristics at
      presentation regardless of their MYD88 status, except that those harboring the
      MYD88 mutation were older (P = .006) and had more frequent involvement of the leg
      (P = .008). Patients harboring the MYD88 mutation had 3- and 5-year-specific
      survival rates of 65.7% and 60.2% vs 85.4% and 71.7% in patients with the wild
      type allele. The MYD88 mutation was significantly associated with shorter disease
      specific survival in univariate (P = .03) and multivariate (odds ratio, 3.01; 95%
      CI, 1.03-8.78; P = .04) analysis. There was no significant difference between the
      groups in their treatment regimens. Considering overall survival, in univariate
      (P = .002) and multivariate (odds ratio, 2.94; 95% CI, 1.18-7.30; P = .02)
      analysis, MYD88 L265P mutation was an independent adverse prognostic factor.
      CONCLUSIONS AND RELEVANCE: This study confirms the high prevalence of MYD88 L265P
      mutation in PCLBCL-LT and shows its association with shorter survival. The
      clinical effect of MYD88 mutation activating the nuclear factor-kappaB pathway
      supports the use of targeted therapies at the time of relapse after conventional
      therapies.

PMID- 25055134
TI  - Addressing prediabetes in childhood obesity treatment programs: support from
      research and current practice.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) and prediabetes have increased in
      prevalence among overweight and obese children, with significant implications for
      long-term health. There is little published evidence on the best approaches to
      care of prediabetes among overweight youth or the current practices used across
      pediatric weight management programs. METHODS: This article reviews the
      literature and summarizes current practices for screening, diagnosis, and
      treatment of prediabetes at childhood obesity treatment centers. Findings
      regarding current practice were based on responses to an online survey from 28
      pediatric weight management programs at 25 children's hospitals in 2012. Based on
      the literature reviewed, and empiric data, consensus support statements on
      prediabetes care and T2DM prevention were developed among representatives of
      these 25 children's hospitals' obesity clinics. RESULTS: The evidence reviewed
      demonstrates that current T2DM and prediabetes diagnostic parameters are derived
      from adult-based studies with little understanding of clinical outcomes among
      youth. Very limited evidence exists on preventing progression of prediabetes.
      Some evidence suggests that a significant proportion of obese youth with
      prediabetes will revert to normoglycemia without pharmacological management.
      Evidence supports lifestyle modification for children with prediabetes, but
      further study of specific lifestyle changes and pharmacological treatments is
      needed. CONCLUSION: Evidence to guide management of prediabetes in children is
      limited. Current practice patterns of pediatric weight management programs show
      areas of variability in practice, reflecting the limited evidence base. More
      research is needed to guide clinical care for overweight youth with prediabetes.

PMID- 25055138
TI  - Long-term survival in patients undergoing percutaneous interventions with or
      without intracoronary pressure wire guidance or intracoronary ultrasonographic
      imaging: a large cohort study.
AB  - IMPORTANCE: Intracoronary pressure wire-derived measurements of fractional flow
      reserve (FFR) and intravascular ultrasonography (IVUS) provide functional and
      anatomical information that can be used to guide coronary stent implantation.
      Although these devices are widely used and recommended by guidelines, limited
      data exist about their effect on clinical end points. OBJECTIVE: To determine the
      effect on long-term survival of using FFR and IVUS during percutaneous coronary
      intervention (PCI). DESIGN AND SETTING: Cohort study based on the pan-London
      (United Kingdom) PCI registry. In total, 64,232 patients are included in this
      registry covering the London, England, area. PARTICIPANTS: All patients (n =
      41,688) who underwent elective or urgent PCI in National Health Service hospitals
      in London between January 1, 2004, and July 31, 2011, were included. Patients
      with ST-segment elevation myocardial infarction (n = 11,370) were excluded.
      INTERVENTIONS: Patients underwent PCI guided by angiography (visual lesion
      assessment) alone, PCI guided by FFR, or IVUS-guided PCI. MAIN OUTCOMES AND
      MEASURES: The primary end point was all-cause mortality at a median of 3.3 years.
      RESULTS: Fractional flow reserve was used in 2767 patients (6.6%) and IVUS was
      used in 1831 patients (4.4%). No difference in mortality was observed between
      patients who underwent angiography-guided PCI compared with patients who
      underwent FFR-guided PCI (hazard ratio, 0.88; 95% CI, 0.67-1.16; P = .37).
      Patients who underwent IVUS had a slightly higher adjusted mortality (hazard
      ratio, 1.39; 95% CI, 1.09-1.78; P = .009) compared with patients who underwent
      angiography-guided PCI. However, this difference was no longer statistically
      significant in a propensity score-based analysis (hazard ratio, 1.33; 95% CI,
      0.85-2.09; P = .25). The mean (SD) number of implanted stents was lower in the
      FFR group (1.1 [1.2] stents) compared with the IVUS group (1.6 [1.3]) and the
      angiography-guided group (1.7 [1.1]) (P < .001). CONCLUSIONS AND RELEVANCE: In
      this large observational study, FFR-guided PCI and IVUS-guided PCI were not
      associated with improved long-term survival compared with standard angiography
      guided PCI. The use of FFR was associated with the implantation of fewer stents.

PMID- 25055139
TI  - LPS-induced dental pulp inflammation increases expression of ionotropic
      purinergic receptors in rat trigeminal ganglion.
AB  - Severe toothache can be caused by dental pulp inflammation. The ionotropic
      purinergic receptor family (P2X) is reported to mediate nociception in primary
      afferent neurons. This study aims to investigate the involvement of P2X receptors
      in the sensitization of the trigeminal ganglion (TG) caused by dental pulp
      inflammation. Lipopolysaccharides were unilaterally applied to the pulp of the
      upper molar of the rat to induce dental pulp inflammation. Increased expression
      of c-fos, a marker of neuronal activity, was induced in V1-V2 division,
      indicating the activation of TG neurons. The expressions of P2X2, P2X3, and P2X5
      were also increased in the V1-V2 division of TG, primarily in small-sized and
      medium-sized neurons. Markers of glutamatergic afferents, VGluT1, and GABAergic
      afferents, GAD67, were induced by lipopolysaccharides and coexpressed with P2X in
      small-sized TG neurons. The present findings suggest that the P2X2, P2X3, and
      P2X5 receptors are upregulated as part of the sensitization produced by dental
      pulp inflammation.

PMID- 25055140
TI  - Epigenetic upregulation of Cdk5 in the dorsal horn contributes to neuropathic
      pain in rats.
AB  - Numerous reports have shown that cyclin-dependent kinase 5 (Cdk5), a proline
      directed serine/threonine kinase, critically contributes to the induction and
      maintenance of chronic pain induced by peripheral inflammation and nerve injury.
      Recent evidence has also suggested the critical role of an epigenetic mechanism
      in the setting of chronic pain. The present study aims to elucidate the cyclic
      AMP response element-binding protein (CREB)-mediated upregulation of Cdk5 and its
      functional significance in rats with neuropathic pain induced by chronic
      constriction injury (CCI) in the sciatic nerve. Significantly increased
      expression of Cdk5 was observed in the dorsal horn of rats with CCI, and
      intrathecal delivery of Cdk5 inhibitor roscovitine significantly attenuated the
      mechanical allodynia in these rats. Phosphorylation of CREB and its occupancy in
      the Cdk5 promoter region was also increased in the dorsal horn, which led to
      increased histone H4 acetylation in the Cdk5 promoter region and the upregulated
      transcription of Cdk5. Inhibition of CREB activity attenuated the upregulation of
      Cdk5 and alleviated the mechanical allodynia in rats with CCI. These results
      demonstrated a CREB-mediated epigenetic upregulation of Cdk5 in the dorsal horn,
      which critically contributed to the maintenance of painful behavior in the rats
      with neuropathic pain. 

PMID- 25055141
TI  - Primate area V1: largest response gain for receptive fields in the straight-ahead
      direction.
AB  - Although neuronal responses in behaving monkeys are typically studied while the
      monkey fixates straight ahead, it is known that eye position modulates responses
      of visual neurons. The modulation has been found to enhance neuronal responses
      when the receptive field is placed in the straight-ahead position for neurons
      receiving input from the peripheral but not the central retina. We studied the
      effect of eye position on the responses of V1 complex cells receiving input from
      the central retina (1.1-5.7 degrees  eccentricity) while minimizing the effect of
      fixational eye movements. Contrast response functions were obtained separately
      with drifting light and dark bars. Data were fit with the Naka-Rushton equation:
      r(c)=Rmax*c/(c+c50)+s, where r(c) is mean spike rate at contrast c, Rmax is the
      maximum response, c50 is the contrast that elicits half of Rmax, and s is the
      spontaneous activity. Contrast sensitivity as measured by c50 was not affected by
      eye position. For dark bars, there was a statistically significant decline in the
      normalized Rmax with increasing deviation from straight ahead. Data for bright
      bars showed a similar trend with a less rapid decline. Our results indicate that
      neurons representing the central retina show a bias for the straight-ahead
      position resulting from modulation of the response gain without an accompanying
      modulation of contrast sensitivity. The modulation is especially obvious for dark
      stimuli, which might be useful for directing attention to hazardous situations
      such as dark holes or shadows concealing important objects (Supplement 1: Video
      Abstract, Supplemental digital content 1, http://links.lww.com/WNR/A295). 

PMID- 25055142
TI  - Intensity-dependent effects of transcranial pulsed current stimulation on
      interhemispheric connectivity: a high-resolution qEEG, sham-controlled study.
AB  - Defining optimal parameters for stimulation is a critical step in the development
      of noninvasive neuromodulation techniques. Transcranial pulsed current
      stimulation (tPCS) is emerging as another option in the field of neuromodulation;
      however, little is known about its mechanistic effects on electrical brain
      activity and how it can modulate its oscillatory patterns. The aim of this study
      was to identify the current intensity needed to exert an effect on quantitative
      electroencephalogram (qEEG) measurements. Forty healthy volunteers were
      randomized to receive a single session of sham or active stimulation at 0.2, 1,
      or 2 mA current intensity with a random frequency with an oscillatory pulsed
      range between 1 and 5 Hz. We conducted an exploratory frequency domain analysis
      to detect changes in absolute power for theta, alpha, and beta frequency bands
      and also interhemispheric coherence for alpha, theta, and four different sub
      bands. Cognitive and nonspecific adverse effects were also recorded. Our results
      showed that both 1 and 2 mA can modulate interhemispheric coherence at the fronto
      temporal areas for the theta band as compared with sham, while 2 mA also
      increased the low-beta and high-beta interhemispheric coherence at the same
      anatomical location. There were no group differences for adverse effects and
      participants could not guess correctly whether they received active versus sham
      stimulation. On the basis of our results, we conclude that tPCS is associated
      with an intensity-dependent facilitatory effect on interhemispheric connectivity.
      These results can guide future tPCS applications and will define its role as a
      neuromodulatory technique in the field.

PMID- 25055143
TI  - Effect of local application of an antibody against brain-derived neurotrophic
      factor on neuroma formation after transection of the inferior alveolar nerve in
      the rat.
AB  - This study aimed to examine the contributions of brain-derived neurotrophic
      factor (BDNF) at the injury site toward neuroma formation and nerve regeneration
      after inferior alveolar nerve transection. Histological analysis confirmed
      neuroma formation at 2 weeks after complete transection of the inferior alveolar
      nerve. A local administration of an antibody to BDNF inhibited connective tissue
      proliferation at the injury site and promoted nerve fiber integrity. Fluorogold
      labeling showed a significantly higher number of labeled cells in the trigeminal
      ganglion in the anti-BDNF-treated group compared with the vehicle control group.
      In-situ hybridization histochemistry showed intense signals for tropomyosin
      receptor kinase B mRNA in the area of the injury site containing fibrous or
      granular tissue in the anti-BDNF-treated group. In contrast, these signals were
      close to the detection limit in the area of the perineurium in intact nerve
      trunks, indicating that the signals were expressed by fibroblasts within the
      connective tissue. These findings suggest that antagonization of endogenous BDNF
      induced by nerve injury reduces neuroma formation, without inhibiting damaged
      axon regeneration.

PMID- 25055144
TI  - Evaluation of microbial contamination of corneal transplants: one-year report
      from a French regional eye bank.
AB  - PURPOSE: The aim of this study was to report the rate of corneal transplant
      microbial contamination in a single major eye bank and to identify the
      contributive factors. METHODS: The contamination rate of 1156 organ-cultured
      corneas harvested in 2010 in a single eye bank (EFS Bourgogne Franche-Comte,
      Besancon, France) was studied together with the following factors: age, sex,
      tissue-recovery method (single or multiorgan donors), death-to-excision time,
      excision-to-reception time, cause of death, positive serology, and endothelial
      cell count. Student t test for quantitative data was used for statistical
      comparisons between groups. Qualitative data were assessed using the chi test.
      RESULTS: The contamination rate was 5.5%. Most contaminations were of bacterial
      origin (77.9%), with Staphylococcus species (62.3%) being predominant. Fungal
      contaminations (19.1%) were dominated by Candida species (76.9%). Death resulting
      from cancer was related to a higher risk of corneal contamination (P < 0.001).
      The other factors were not related to an increased risk of contamination.
      CONCLUSIONS: The rate of microbiological contamination of corneal transplants
      remains low. However, special caution should be exercised with grafts collected
      from patients dying from cancer. To minimize this risk, further studies on the
      antibacterial effect of the conservation media should be conducted in the context
      of increased bacterial resistance.

PMID- 25055145
TI  - One-year clinical study on efficacy of corneal cross-linking in Indian children
      with progressive keratoconus.
AB  - PURPOSE: The aim of this study was to assess the efficacy of corneal collagen
      cross-linking (CXL) with riboflavin using ultraviolet-A light in children with
      progressive keratoconus. METHODS: Thirty-five eyes of 24 children with
      progressive keratoconus aged between 9 and 16 years were included in this
      retrospective study. Ocular examination included the best-corrected visual acuity
      (BCVA), dilated refraction, slit-lamp exam, and corneal topography (Orbscan II)
      at 6 and 12 months. All children were treated with riboflavin with ultraviolet-A
      light under topical anesthesia and all completed 1-year follow-up. RESULTS: The
      mean age of the children was 13.65 years (range, 9-16 years). Follow-up was for a
      period of 1 year. The mean of preoperative keratometry (Kmax) was 55.11 +/- 5.34
      diopters (D), whereas the mean of postoperative Kmax was reduced to 53.87 +/-
      4.99 D. The mean preoperative pachymetry was 412.31 +/- 36.54 MUm, which changed
      to 361.31 +/- 58.04 MUm postoperatively. At 1 year, improvement in the BCVA was
      noted in 18 (51.42%) eyes, stabilization in 12 (34.28%), and worsening in 5
      (14.28%) eyes. Overall, the BCVA improved by 1 line, which was statistically
      significant (P = 0.0368) at the end of 1 year. There was a reduction in both
      cylindrical and spherical equivalent, of which, the latter was not statistically
      significant (P = 0.77), whereas the former was of weak statistical significance
      (P = 0.061). No complications were reported. CONCLUSIONS: CXL with riboflavin is
      an effective procedure for children with progressive keratoconus. The results
      show stabilization, improvement, or both in keratoconus in terms of BCVA and
      corneal curvature after CXL in most children.

PMID- 25055147
TI  - Lattice corneal dystrophy type 1: an epithelial or stromal entity?
AB  - PURPOSE: To evaluate the question whether lattice corneal dystrophy type 1 (LCD1)
      is of epithelial or stromal origin. METHODS: The landmark of advanced LCD1 shows
      central superficial haze and paracentral stromal lattice lines. In 16 eyes of 8
      affected individuals of 2 families, a penetrating keratoplasty was performed. The
      follow-up was 8 to 16 years after penetrating keratoplasty. Slit-lamp
      documentation of the patients was evaluated in direct and indirect illumination
      with dilated pupil to assess the horizontal and vertical pattern of new deposits
      on the corneal graft. Three affected patients of 2 families are demonstrated in
      detail. A DNA analysis was performed. RESULTS: Gene identification revealed a
      transforming growth factor beta-induced (TGFBI) Leu509Pro mutation in the first
      family, and a TGFBI Arg124Cys mutation in the second family. The demonstrated 5
      corneal grafts of the 3 LCD1-patients showed diffuse opacities of distinct
      severity, beginning 3 to 4 years postoperatively, that were often combined with
      corneal erosions and consecutive pain. In none of our patients, we were able to
      detect any signs of lattice formation in the form of gray lines that run
      obliquely from the surface to the midstroma in direct illumination. In
      retroillumination, no lattice opacity units in the form of translucent and
      refractile lines were visible on the graft. CONCLUSIONS: The TGFBI gene, that is
      responsible for LCD1, is expressed above all by the corneal epithelial cells but
      also by the keratocytes. We interpret the superficial diffuse LCD1 recurrences on
      the graft as the product of the epithelial cells, whereas the nonoccurrence of
      lattice lines as long as 18 years after keratoplasty, an indirect sign that the
      lattice lines are the product of the keratocytes. Thus, LCD1 seems to represent
      an epithelial-stromal entity, because both epithelial cells and keratocytes are
      involved.

PMID- 25055146
TI  - Association between transient interface fluid on intraoperative OCT and textural
      interface opacity after DSAEK surgery in the PIONEER study.
AB  - PURPOSE: The aim of this study was to examine the association between transient
      interface fluid (TIF) and textural interface opacity (TIO) after Descemet
      stripping automated endothelial keratoplasty (DSAEK) surgery using intraoperative
      optical coherence tomography (iOCT) in the PIONEER (Prospective Intraoperative
      and Perioperative Ophthalmic ImagiNg with Optical CoherEncE TomogRaphy) study.
      METHODS: All consecutive eyes that underwent DSAEK between October 2011 and
      September 2013 from the PIONEER intraoperative and perioperative OCT study were
      included. iOCT images were captured after lenticule apposition with complete air
      fill and after air-fluid exchange. Postoperative day 1 OCT images were obtained.
      Outcome variables included the presence of TIO at the graft-host junction and the
      presence of intraoperative and postoperative interface fluid on OCT. RESULTS:
      Seventy-six eyes from 69 patients who underwent DSAEK with iOCT were included.
      The mean age of the patients was 71 years (range 31-90). The 2 most common
      indications for surgery were Fuchs dystrophy (63%) and pseudophakic bullous
      keratopathy (24%). In 18 of 76 (23.7%) eyes, TIF was visible on iOCT post air
      fluid exchange. Of these eyes, 14 developed TIO. TIO was observed in 18 of 76
      (23.7%) eyes. TIF on iOCT was associated with a significantly higher rate of
      postoperative TIO (odds ratio = 47.25; P < 0.0001). Sixteen of the 18 eyes that
      had TIF on iOCT had had resolution on the postoperative day 1 OCT. There was no
      significant difference in the mean graft thickness between eyes with TIF on iOCT
      and those without (P = 0.58). CONCLUSIONS: Eyes with TIF on iOCT are more likely
      to develop TIO in the postoperative period. It is believed that the process of
      gap closure results in TIO, possibly secondary to precipitated solutes, retained
      viscoelastic, or lamellar irregularities caused by delayed adhesion or uneven
      matching of lamellar fibrils.

PMID- 25055148
TI  - Objective assessment of squamous metaplasia of conjunctival epithelial cells as
      associated with soft contact lens wear versus non-lens wearers.
AB  - PURPOSE: To objectively assess the morphology of superficial conjunctival surface
      cells showing squamous metaplasia as seen in contact lens wearers. METHODS:
      Impression cytology samples were taken from interpalpebral bulbar conjunctiva
      from 23 young adult white European women with an average of 6 years of successful
      daily soft contact lens wear and 23 non-contact-lens-wearing women of the same
      age. Cell images were graded, and cell and nuclear dimensions and areas were
      measured by planimetry. RESULTS: The contact lens wearers had a mean squamous
      metaplasia grade (Nelson) of 2.74 versus 0.35 for the non-lens wearers, with the
      cell longest dimension (LONG) being 54.4 +/- 5.6 MUm versus 22.4 +/- 2.9 MUm,
      respectively (P < 0.001). Similar differences were found for the cell shortest
      dimension (SHORT) and cell area values (P < 0.001). The cell nuclei in the
      contact lens wearers, based on measures of cell nuclear length (NUCLONG), were
      12.7 +/- 1.7 MUm versus 10.0 +/- 1.1 MUm (P < 0.001) with no evidence of pyknotic
      (shrunken) nuclei. The nucleo-cytoplasmic ratios had mean values of 3.603 versus
      1.282 for the cytoplasm-to-nucleus length (CYT/NUC length) ratio, and 0.075 and
      0.319 for the NU/CYT length ratio for contact lens wearers and non-wearers,
      respectively. CONCLUSIONS: As squamous metaplasia develops, at least in long-term
      soft contact lens wearers, the conjunctival surface cells become considerably
      enlarged, but the nuclear size of these cells also increases, rather than showing
      signs of pyknosis.

PMID- 25055149
TI  - Impact of intraoperative topical hydroxypropyl methylcellulose 2% versus sodium
      hyaluronate 1.2% on corneal reepithelialization after intentional epithelial
      debridement during vitrectomy.
AB  - PURPOSE: The aim of this study was to assess the impact of the intraoperative use
      of topical hydroxypropyl methylcellulose (HPMC) 2% versus sodium hyaluronate 1.2%
      on corneal reepithelialization time and final corneal status after intentional
      epithelial debridement during vitrectomy for proliferative vitreoretinopathy.
      METHODS: Forty eyes of 40 patients were included in the study, divided into 2
      groups of 20 eyes. HPMC 2% and sodium hyaluronate 1.2% were used as corneal
      protectors in the first and second group, respectively. Patients' charts were
      reviewed to determine any differences between the HPMC 2% and sodium hyaluronate
      1.2% groups in relation to the preoperative, intraoperative, and postoperative
      factors that could impact postoperative corneal reepithelialization.
      Postoperative reepithelialization time and final corneal status were recorded.
      RESULTS: No significant between-group differences in preoperative,
      intraoperative, and postoperative factors were found. Reepithelialization time
      was significantly shorter in the sodium hyaluronate 1.2% group than in the HPMC
      2% group, although reepithelialization was eventually achieved in every patient
      in both groups. Corneal sequelae were significantly more frequent in the HPMC 2%
      group than in the sodium hyaluronate 1.2% group. CONCLUSIONS: The choice of the
      ophthalmic viscosurgical device for intraoperative corneal protection may
      significantly influence the postoperative corneal status after complicated
      retinal detachment.

PMID- 25055150
TI  - Intrastromal antifungal injection with secondary lamellar interface infusion for
      late-onset infectious keratitis after DSAEK.
AB  - PURPOSE: The aim of this study was to report the successful medical management of
      2 cases of late-onset endothelial keratoplasty-related stromal interface
      infections. METHODS: All cases of endothelial keratoplasty-related infections
      treated with intrastromal antifungal injections were compiled. The following
      information was collected: demographic data, surgical indications, donor rim
      cultures, donor mate outcomes, clinical course, diagnostic tests, and clinical
      outcome. RESULTS: Two cases of interface fungal keratitis diagnosed on clinical
      appearance and confocal microscopy were identified. Both patients refused to
      undergo further surgery and failed systemic and/or topical therapy. Each received
      3 to 4 intrastromal injections, with secondary infusion into the graft-host
      interface, which resulted in the complete involution of their interface
      opacities. CONCLUSIONS: Intrastromal antifungal injection may be an effective
      alternative to surgical intervention in late-onset fungal Descemet stripping
      endothelial keratoplasty interface keratitis. Early treatment may preserve graft
      viability and result in a good visual outcome without the need for either
      penetrating keratoplasty or potential pathogen exposure to the anterior chamber.

PMID- 25055151
TI  - Boston type 1 keratoprosthesis for chemical and thermal injury.
AB  - PURPOSE: To evaluate the outcome of the Boston type 1 keratoprosthesis (Kpro-1)
      in eyes with failed interventions for chemical and thermal injury. METHODS: A
      retrospective review was performed of every eye with chemical or thermal injury
      that was treated with a Kpro-1 at a tertiary eye care center between January 1,
      2008 and July 1, 2013. The main outcome measures were visual outcome, prosthesis
      retention, and postoperative complications. RESULTS: Nine eyes met the inclusion
      criteria, including 7 eyes with alkali burns, 1 eye with an acid burn, and 1 eye
      with a thermal burn. After a mean follow-up of 40.7 months (range, 29-60 months),
      the median best-corrected visual acuity was 20/60 (range, 20/15 to no light
      perception). One eye was >=20/20, 3 eyes were >=20/40, and 6 eyes were >=20/70.
      The initial Kpro-1 prosthesis was retained in 7 (77.7%) eyes and successfully
      replaced in the other 2 eyes. One or more serious complications occurred in 6
      (66.7%) eyes. These included 2 cases of sterile corneal ulceration with
      prosthesis extrusion, 2 cases of microbial keratitis (1 bacterial and 1 fungal),
      2 cases of bacterial endophthalmitis, and 2 cases of retinal detachments. These
      complications contributed to visual outcomes of hand motions in 2 eyes and no
      light perception in 1 eye. CONCLUSIONS: The Boston Kpro-1 is associated with
      highly satisfactory visual outcomes and prosthesis retention in most cases of
      severe chemical or thermal injury. Serious complications are common and may
      compromise the final outcome.

PMID- 25055152
TI  - Additive Effect of preservative-free sodium hyaluronate 0.1% in treatment of dry
      eye syndrome with diquafosol 3% eye drops.
AB  - PURPOSE: The aim of this study was to evaluate the treatment effect of diquafosol
      3% with preservative-free sodium hyaluronate 0.1% eye drops in dry eye syndrome.
      METHODS: In total, 150 patients with dry eye syndrome were divided randomly into
      3 groups. Group 1 (50 patients) was treated 4 times daily with preserved sodium
      hyaluronate 0.1%, group 2 (50 patients) was treated 4 times daily with diquafosol
      3%, and group 3 (50 patients) was treated 4 times daily with diquafosol 3% and
      preservative-free sodium hyaluronate 0.1% eye drops for 3 months. Ocular surface
      disease index (OSDI) score, tear film break-up time, Schirmer I test, corneal
      fluorescein staining, and impression cytology were evaluated. RESULTS: There were
      significant improvements in the OSDI score, tear film break-up time, Schirmer I
      score, fluorescein and Rose Bengal staining, goblet cell density, and impression
      cytological findings in groups 2 and 3 compared with those for group 1 in
      patients with dry eye syndrome at 1, 2, and 3 months (P < 0.05). There were
      statistically significant improvements in the OSDI score (-8.48 +/- 0.97, -5.69
      +/- 0.78; P = 0.02), fluorescein (-1.43 +/- 0.21, -1.02 +/- 0.18; P = 0.03), and
      Rose Bengal staining (-1.12 +/- 0.26, -0.75 +/- 0.12; P = 0.03), goblet cell
      density (89.65 +/- 14.39, 70.36 +/- 16.75; P = 0.03), and impression cytological
      findings (-0.53 +/- 0.12, -0.34 +/- 0.90; P = 0.01) in group 3 compared with
      those in group 2 at 3 months. CONCLUSIONS: Treatment with diquafosol 3% with
      preservative-free sodium hyaluronate 0.1% was more effective than diquafosol 3%
      monotherapy or treatment with preserved sodium hyaluronate 0.1% in dry eye
      syndrome. Preservative-free sodium hyaluronate 0.1% eye drops can increase the
      effect of diquafosol 3% in dry eye syndrome.

PMID- 25055153
TI  - A small amount of dietary carbohydrate can promote the HFD-induced insulin
      resistance to a maximal level.
AB  - Both dietary fat and carbohydrates (Carbs) may play important roles in the
      development of insulin resistance. The main goal of this study was to further
      define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice
      were fed normal chow diet (CD) or HFD containing 0.1-25.5% carbs for 5 weeks,
      followed by evaluations of calorie consumption, body weight and fat gains,
      insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative
      stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the
      HFD-induced insulin resistance was determined in mice. The role of fat in insulin
      resistance was also examined in cultured cells. HFD with little carbs (0.1%)
      induced severe insulin resistance. Addition of 5% carbs to HFD dramatically
      elevated insulin resistance and 10% carbs in HFD was sufficient to induce a
      maximal level of insulin resistance. HFD with little carbs induced ectopic fat
      accumulation and oxidative stress in liver and skeletal muscle and addition of
      carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD
      increased hepatic expression of key gluconeogenic genes and the increase was most
      dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis
      prevented the HFD-induced insulin resistance. In cultured cells, development of
      insulin resistance induced by a pathological level of insulin was prevented in
      the absence of fat. Together, fat is essential for development of insulin
      resistance and dietary carb is not necessary for HFD-induced insulin resistance
      due to the presence of hepatic gluconeogenesis but a very small amount of it can
      promote HFD-induced insulin resistance to a maximal level. 

PMID- 25055154
TI  - Dose-toxicity relationship of gadoxetate disodium and transient severe
      respiratory motion artifact.
AB  - OBJECTIVE: The purpose of this article is to determine whether there is a dose
      toxicity relationship between gadoxetate disodium and transient severe
      respiratory motion artifact. MATERIALS AND METHODS: Gadoxetate disodium-enhanced
      MRI studies (559 studies of 559 patients) using a fixed 20-mL (2 mL/s; n = 112)
      or 10-mL (1-2 mL/s; n = 447) volume at two health systems were included (dose
      range, 0.05-0.42 mL/kg; mean, 0.15 mL/kg; above-label dosing, 479 [86%]). Each
      dynamic phase was assigned a respiratory motion score from 1 (none) to 5
      (nondiagnostic). Examinations with an unenhanced score of 1-2, arterial score of
      4-5, and venous or late-dynamic scores of 1-3 were labeled as transient severe
      respiratory motion artifact. Stepwise multivariate logistic regression was
      performed. RESULTS: The overall incidence of transient severe respiratory motion
      artifact was 12% (67/559; site 1, 15% [35/232]; site 2, 9.8% [32/327]). The
      administered volume of contrast material had a statistically significant effect
      (20 mL, 20% [22/112] vs 10 mL, 10%, [45/447]; multivariate p = 0.01; odds ratio,
      2.1 [20 vs 10 mL]; 95% CI, 1.2-3.7). There was no dose-toxicity relationship for
      dose-by-weight (p = 0.61 [multivariate]) or above-label dosing (p = 0.88
      [univariate]; 13% [10/80] rate for at- or below-label dosing vs 12% [57/479] rate
      for above-label dosing). Chronic obstructive pulmonary disease was the only non
      dose-related predictor in the multivariate model (p < 0.0001; OR, 5.1 [95% CI,
      2.5-11.5]; 39% [12/31] vs 10% [55/528]). CONCLUSION: Gadoxetate disodium
      associated transient severe respiratory motion artifact is significantly more
      common after 20-mL administration (2 mL/s) and occurs significantly more often in
      patients with chronic obstructive pulmonary disease. The volume-related effect
      suggests a nonallergiclike mechanism.

PMID- 25055155
TI  - Survival and functional outcomes after hip fracture among nursing home residents.
AB  - IMPORTANCE: Little is known regarding outcomes after hip fracture among long-term
      nursing home residents. OBJECTIVE: To describe patterns and predictors of
      mortality and functional decline in activities of daily living (ADLs) among
      nursing home residents after hip fracture. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective cohort study of 60,111 Medicare beneficiaries residing in nursing
      homes who were hospitalized with hip fractures between July 1, 2005, and June 30,
      2009. MAIN OUTCOMES AND MEASURES: Data sources included Medicare claims and the
      Nursing Home Minimum Data Set. Main outcomes included death from any cause at 180
      days after fracture and a composite outcome of death or new total dependence in
      locomotion at the latest available assessment within 180 days. Additional
      analyses described within-residents changes in function in 7 ADLs before and
      after fracture. RESULTS: Of 60,111 patients, 21,766 (36.2%) died by 180 days
      after fracture; among patients not totally dependent in locomotion at baseline,
      53.5% died or developed new total dependence within 180 days. Within individual
      patients, function declined substantially after fracture across all ADL domains
      assessed. In adjusted analyses, the greatest decreases in survival after fracture
      occurred with age older than 90 years (vs <=75 years: hazard ratio [HR], 2.17;
      95% CI, 2.09-2.26 [P < .001]), nonoperative fracture management (vs internal
      fixation: HR for death, 2.08; 95% CI, 2.01-2.15 [P < .001]), and advanced
      comorbidity (Charlson score of >=5 vs 0: HR, 1.66; 95% CI, 1.58-1.73 [P < .001]).
      The combined risk of death or new total dependence in locomotion within 180 days
      was greatest among patients with very severe cognitive impairment (vs intact
      cognition: relative risk [RR], 1.66; 95% CI, 1.56-1.77 [P < .001]), patients
      receiving nonoperative management (vs internal fixation: RR, 1.48; 95% CI, 1.45
      1.51 [P < .001]), and patients older than 90 years (vs <=75 years: RR, 1.42; 95%
      CI, 1.37-1.46 [P < .001]). CONCLUSIONS AND RELEVANCE: Survival and functional
      outcomes are poor after hip fracture among nursing home residents, particularly
      for patients receiving nonoperative management, the oldest old, and patients with
      multiple comorbidities and advanced cognitive impairment. Care planning should
      incorporate appropriate prognostic information related to outcomes in this
      population.

PMID- 25055157
TI  - Fecal source tracking in water by next-generation sequencing technologies using
      host-specific Escherichia coli genetic markers.
AB  - High levels of fecal bacteria are a concern for the aquatic environment, and
      identifying sources of those bacteria is important for mitigating fecal pollution
      and preventing waterborne disease. Escherichia coli has been used as an indicator
      of fecal pollution, however less success has been achieved using this organism
      for library-independent microbial source tracking. In this study, using next
      generation sequencing technology we sequenced the whole genomes of 22 E. coli
      isolates from known sources (9 from humans, 2 from cows, 6 from pigs, and 5 from
      chickens) and identified candidate host-specific genomic regions. Specificity
      testing on the candidate regions was performed using 30 E. coli isolates from
      each source. Finally, we identified 4 human-, 2 cow-, 3 pig-, and 4 chicken
      specific genetic markers useful for source tracking. We also found that a
      combination of multiplex PCR and dual index sequencing is effective for detecting
      multiple genetic markers in multiple isolates at one time. This technique was
      applied to investigating identified genetic markers in 549 E. coli isolates
      obtained from the Yamato River, Japan. Results indicate that humans constitute a
      major source of water contamination in the river. However, further work must
      include isolates obtained from geographically diverse animal hosts to make this
      method more reliable. 

PMID- 25055158
TI  - Chemical composition and antifungal activity of supercritical extract and
      essential oil of Tanacetum vulgare growing wild in Lithuania.
AB  - This article reports the results concerning the qualitative and quantitative
      composition of the volatile oil obtained from the aerial parts of Tanacetum
      vulgare, collected in Lithuania, by supercritical fluid extraction (SFE) with CO2
      at 90 bar and 40  degrees C and by hydrodistillation (HD). GC-MS and GC-FID
      analysis revealed that the oils mainly consisted of 1,8-cineole, trans-thujone,
      cis-chrysanthenol, borneol and myrtenol. Oils obtained by HD displayed, with
      respect to the SFE volatile oil, a higher amount of hydrocarbon monoterpenes. The
      hydrodistilled oil was particularly active against dermatophyte strains and
      Cryptococcus neoformans, with MIC values in the range of 0.16-0.64 MUL/mL. The
      oil revealed a significant inhibitory effect on germ tube formation in Candida
      albicans at sub-inhibitory concentrations. At the concentration of 1/16 MIC, the
      inhibition of filamentation was more than 80% in comparison to untreated control
      cells.

PMID- 25055156
TI  - MiRiad Roles for MicroRNAs in Cardiac Development and Regeneration.
AB  - Cardiac development is an exquisitely regulated process that is sensitive to
      perturbations in transcriptional activity and gene dosage. Accordingly,
      congenital heart abnormalities are prevalent worldwide, and are estimated to
      occur in approximately 1% of live births. Recently, small non-coding RNAs, known
      as microRNAs, have emerged as critical components of the cardiogenic regulatory
      network, and have been shown to play numerous roles in the growth,
      differentiation, and morphogenesis of the developing heart. Moreover, the
      importance of miRNA function in cardiac development has facilitated the
      identification of prospective therapeutic targets for patients with congenital
      and acquired cardiac diseases. Here, we discuss findings attesting to the
      critical role of miRNAs in cardiogenesis and cardiac regeneration, and present
      evidence regarding the therapeutic potential of miRNAs for cardiovascular
      diseases. 

PMID- 25055159
TI  - Jiri Prochaska (1749-1820): Part 2: "De structura nervorum"--studies on a
      structure of the nervous system.
AB  - The treatise "De structura nervorum" by Jiri Prochaska was published in 1779 and
      is remarkable not only for its anatomical and histological findings but also for
      its historical introduction, which contains a detailed bibliographical review of
      the contemporary knowledge of the structure of the nervous tissue. Unfortunately,
      the treatise has never been translated from the Latin language, but it deserves
      further analysis as a historical document about the level of neuroscience
      research conducted by a famous Czech scholar. The present article includes a
      historical overview of the contemporary knowledge of the structure of the nervous
      tissue up to the late eighteenth century from the perspective of today, a
      translation of selected chapters from Prochaska's treatise (a historical
      introduction about the medieval knowledge of the structure of the nervous tissue
      and an interpretation of his neurohistological observations), and an analysis of
      Jiri Prochaska's results in light of current knowledge. 

PMID- 25055160
TI  - Pickering emulsions: what are the main parameters determining the emulsion type
      and interfacial properties?
AB  - We synthesized surface-active lipophilic core-hydrophilic shell latex particles,
      and we probed their efficiency as emulsion stabilizers. The relative weight
      percentage of the shell, RS/P, was varied to trigger the balance between
      lipophilicity and hydrophilicity of the particles. Particle wettability could
      concomitantly be tuned by the pH of the aqueous phase determining the surface
      charge. Emulsions covering a wide range of RS/P and pH values were fabricated,
      and their type, oil-in-water (O/W) or water-in-oil (W/O), and kinetic stability
      were systematically assessed. By adapting the particle gel trapping technique to
      pH-variable systems and by exploiting the limited coalescence process, we were
      able to determine the proportion of oil/water interfacial area, C, covered by the
      particles as well as their contact angle, theta. All of these data were gathered
      into a single generic diagram showing good correlation between the emulsion type
      and the particle contact angle (O/W for theta < 90 degrees  and W/O for theta >
      90 degrees ) in agreement with the empirical Finkle rule. Interestingly, no
      stable emulsion could be obtained when the wettability was nearly balanced and a
      "bipolar"-like behavior was observed, with the particles adopting two different
      contact angles whose average value was close to 90 degrees . For particles such
      that theta < 90 degrees , O/W emulsions were obtained, and, depending on the pH
      of the continuous phase, the same type of particles and the same emulsification
      process led to emulsions characterized either by large drops densely covered by
      the particles or by small droplets that were weakly covered. The two metastable
      states were also accessible to emulsions stabilized by particles of variable
      origins and morphologies, thus proving the generality of our findings. 

PMID- 25055161
TI  - Pharmacokinetics of an injectable modified-release 2-hydroxyflutamide formulation
      in the human prostate gland using a semiphysiologically based biopharmaceutical
      model.
AB  - The local distribution of 2-hydroxyflutamide (2-HOF) in prostate tissue after a
      single intraprostatic injection of a novel parenteral modified-release (MR)
      formulation in patients with localized prostate cancer was estimated using a
      semiphysiologically based biopharmaceutical model. Plasma concentration-time
      profiles for 2-HOF were acquired from a phase II study in 24 patients and the
      dissolution of the MR formulation was investigated in vitro. Human physiological
      values and the specific physicochemical properties of 2-HOF were obtained from
      the literature or calculated via established algorithms. A compartmental modeling
      approach was adopted for tissue and blood in the prostate gland, where the
      compartments were modeled as a series of concentric spherical shells contouring
      the centrally positioned depot formulation. Discrete fluid connections between
      the blood compartments were described by the representative flow of blood,
      whereas the mass transport of drug from tissue to tissue and tissue to blood was
      described by a one-dimensional diffusion approximation. An empirical dissolution
      approach was adopted for the release of 2-HOF from the formulation. The model
      adequately described the plasma concentration-time profiles of 2-HOF. Predictive
      simulations indicated that the local tissue concentration of 2-HOF within a
      distance of 5 mm from the depot formulation was approximately 40 times higher
      than that of unbound 2-HOF in plasma. The simulations also indicated that
      spreading the formulation throughout the prostate gland would expose more of the
      gland and increase the overall release rate of 2-HOF from the given dose. The
      increased release rate would initially increase the tissue and plasma
      concentrations but would also reduce the terminal half-life of 2-HOF in plasma.
      Finally, an in vitro-in vivo correlation of the release of 2-HOF from the
      parenteral MR formulation was established. This study shows that intraprostatic 2
      HOF concentrations are significantly higher than systemic plasma concentrations
      and that increased distribution of 2-HOF throughout the gland, using strategic
      imaging-guided administration, is possible. This novel parenteral MR formulation,
      thus, facilitates good pharmacological effect while minimizing the risk of side
      effects. 

PMID- 25055162
TI  - Chemical stabilization and improved thermal resilience of molecular arrangements:
      possible formation of a surface network of bonds by multiple pulse atomic layer
      deposition.
AB  - In this work, we make use of an atomic layer deposition (ALD) surface reaction
      based on trimethyl-aluminum (TMA) and water to modify O-H terminated self
      assembled layers of octadecylphosphonic acid (OPA). The structural modifications
      were investigated by X-ray reflectivity, X-ray diffraction, and atomic force
      microscopy. We observed a significant improvement in the thermal stability of ALD
      modified molecules, with the existence of a supramolecular packing structure up
      to 500  degrees C. Following the experimental observations, density functional
      theory (DFT) calculations indicate the possibility of formation of a covalent
      network with aluminum atoms connecting OPA molecules at terrace surfaces.
      Chemical stability is also achieved on top of such a composite surface,
      inhibiting further ALD oxide deposition. On the other hand, in the terrace edges,
      where the covalent array is discontinued, the chemical conditions allow for oxide
      growth. Analysis of the DFT results on band structure and density of states of
      modified OPA molecules suggests that besides the observed thermal resilience, the
      dielectric character of OPA layers is preserved. This new ALD-modified OPA
      composite is potentially suitable for applications such as dielectric layers in
      organic devices, where better thermal performance is required. 

PMID- 25055163
TI  - Computed tomography radiation dosimetry: from the indicators to the indications.
AB  - The technological advances in computed tomography (CT) scanners and their
      continuously increased use have raised concern about the patient-induced risks
      from the CT procedures. In the present review, all available dose metrics used in
      CT dosimetry are described, evaluated, and compared. The various models and
      methodologies currently existing for the estimation of the effective dose and, by
      extension, the carcinogenesis probability as well as the way that this is derived
      from dose descriptors are also considered. 

PMID- 25055164
TI  - Strange magnetic multipoles and neutron diffraction by an iridate perovskite
      (Sr2IrO4).
AB  - A theoretical investigation of a plausible construct for electronic structure in
      iridate perovskites demonstrates the existence of magnetic multipoles hitherto
      not identified. The strange multipoles, which are parity-even, time-odd and even
      rank tensors, are absent from the so-called j(eff) = 1/2 model. We prove that the
      strange multipoles contribute to magnetic neutron diffraction, and we estimate
      their contribution to intensities of Bragg spots for Sr(2)IrO(4). The construct
      encompasses the j(eff) = 1/2 model, and it is consistent with the known magnetic
      structure, ordered magnetic moment, and published resonant x-ray Bragg
      diffraction data. Over and above time-odd quadrupoles and hexadecapoles, whose
      contribution changes neutron Bragg intensities by an order of magnitude,
      according to our estimates, are relatively small triakontadipoles recently
      proposed as the primary magnetic order-parameter of Sr(2)IrO(4).

PMID- 25055166
TI  - Efficacy of anti-fungal but not anti-bacterial prophylaxis in intensive primary
      AML therapy: a real-world, retrospective comparative single-centre study.
AB  - QUESTIONS UNDER STUDY: The optimal strategy of anti-infectious prophylaxis in
      patients with acute leukaemia undergoing intensive chemotherapy remains a matter
      of debate. We assessed the impact of primary prophylaxis with posaconazole and
      levofloxacin on the incidence of invasive fungal infections (IFI) and
      bacteraemia. METHODS: A retrospective single-centre study including two groups of
      adult patients with AML receiving intensive chemotherapy. Group one without anti
      infective prophylaxis (September 2008 - February 2010), and group two with anti
      infective prophyalaxis (March 2010 - April 2011). The primary end-point was IFI
      according to the EORTC/MSG 2008 definitions and bacteraemia. RESULTS: Baseline
      characteristics were similar in the non-prophylaxis (n = 43 patients; 99
      chemotherapy cycles) and the prophylaxis (n = 45; 104 chemotherapy cycles) group.
      IFI were significantly reduced in the prophylaxis group (55.3% vs. 88.9%; p =
      0.0032) and there was a trend of the projected IFI-free survival at 100 days to
      be increased (50.1% vs. 25%; p = 0.0526). One-hundred day overall survival (84.4%
      and 88.4%, p = 0.35) and 2-year overall survival (64.4% and 58.1%; p = 0.64) were
      unaffected. No difference in the occurrence of bacteraemia was observed (32.3%
      vs. 34.6%; p = 0.8). A total of two (3.6%) patients in the non-prophylaxis and
      three (6.7%) in the prophylaxis group died due to IFI, and two (3.6%) in the non
      prophylaxis and none in the prophylaxis group patients had to stop leukaemia
      treatment due to IFI. CONCLUSIONS: The anti-infective prophylaxis with
      posaconazole and levofloxacin resulted in a significant reduction of 'possible'
      IFI with a number-needed to treat to prevent one IFI of only 3 but did not result
      in a reduction of the incidence of bacteraemia.

PMID- 25055167
TI  - Screened coulomb hybrid DFT investigation of band gap and optical absorption
      predictions of CuVO3, CuNbO3 and Cu5Ta11O30 materials.
AB  - We present a joint theoretical and experimental investigation of the
      optoelectronic properties of CuVO3, CuNbO3 and Cu5Ta11O30 materials for potential
      photocatalytic and solar cell applications. In addition to the experimental
      results obtained by powder X-ray diffraction and UV-Vis spectroscopy of the
      materials synthesized under flowing N2 gas at atmospheric pressure via solid
      state reactions, the electronic structure and the UV-Vis optical absorption
      coefficient of these compounds are predicted with high accuracy using advanced
      first-principles quantum methods based on DFT (including the perturbation theory
      approach DFPT) within the screened coulomb hybrid HSE06 exchange-correlation
      formalism. The calculated density of states are found to be in agreement with the
      UV-Vis diffuse reflectance spectra, predicting a small indirect band gap of 1.4
      eV for CuVO3, a direct band gap of 2.6 eV for CuNbO3, and an indirect (direct)
      band gap of 2.1 (2.6) eV for Cu5Ta11O30. It is confirmed that the Cu(I)-based
      multi-metal oxides possess a strong contribution of filled Cu(I) states in the
      valence band and of empty d(0) metal states in the conduction band.
      Interestingly, CuVO3 with its predicted small indirect band gap of 1.4 eV shows
      the highest absorption coefficient in the visible range with a broad absorption
      edge extending to 886 nm. This novel result offers a great opportunity for this
      material to be an excellent candidate for solar cell applications.

PMID- 25055165
TI  - Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with
      systemic lupus erythematosus.
AB  - We evaluated the concentrations of 25-hydroxyvitamin D [25(OH)D] in children and
      adolescents with juvenile systemic lupus erythematosus (JSLE) and associated them
      with disease duration and activity, use of medication (chloroquine and
      glucocorticoids), vitamin D intake, calcium and alkaline phosphatase levels, and
      bone mineral density. Thirty patients with JSLE were evaluated and compared to 30
      healthy individuals, who were age and gender matched. Assessment was performed of
      clinical status, disease activity, anthropometry, laboratory markers, and bone
      mineral density. The 30 patients included 25 (83.3%) females and 16 (53.3%)
      Caucasians, with a mean age of 13.7 years. The mean age at diagnosis was 10.5
      years and mean disease duration was 3.4 years. Mean levels of calcium, albumin,
      and alkaline phosphatase were significantly lower in patients with JSLE compared
      with controls (P<0.001, P=0.006, and P<0.001, respectively). Twenty-nine patients
      (97%) and 23 controls (77%) had 25(OH)D concentrations lower than 32 ng/mL, with
      significant differences between them (P<0.001). Fifteen patients (50%) had
      vitamin D levels <20 ng/mL and 14 had vitamin D levels between 20 and 32 ng/mL.
      However, these values were not associated with greater disease activity, higher
      levels of parathormone, medication intake, or bone mineral density. Vitamin D
      concentrations were similar with regard to ethnic group, body mass index, height
      for age, and pubertal stage. Significantly more frequently than in controls, we
      observed insufficient serum concentrations of 25(OH)D in patients with JSLE;
      however, we did not observe any association with disease activity, higher levels
      of parathormone, lower levels of alkaline phosphatase, use of medications, or
      bone mineral density alterations. 

PMID- 25055168
TI  - Platinum-RNA modifications following drug treatment in S. cerevisiae identified
      by click chemistry and enzymatic mapping.
AB  - With the importance of RNA-based regulatory pathways, the potential for targeting
      noncoding and coding RNAs by small molecule therapeutics is of great interest.
      Platinum(II) complexes including cisplatin (cis-diamminedichloroplatinum(II)) are
      widely prescribed anticancer compounds that form stable adducts on nucleic acids.
      In tumors, DNA damage from Pt(II) initiates apoptotic signaling, but this
      activity is not necessary for cytotoxicity (e.g., Yu et al., 2008), suggesting
      accumulation and consequences of Pt(II) lesions on non-DNA targets. We previously
      reported an azide-functionalized compound, picazoplatin, designed for post
      treatment click labeling that enables detection of Pt complexes (White et al.,
      2013). Here, we report in-gel fluorescent detection of Pt-bound rRNA and tRNA
      extracted from picazoplatin-treated S. cerevisiae and labeled using Cu-free click
      chemistry. These data provide the first evidence that cellular tRNA is a platinum
      drug substrate. We assess Pt(II) binding sites within rRNA from cisplatin-treated
      S. cerevisiae, in regions where damage is linked to significant downstream
      consequences including the sarcin-ricin loop (SRL) Helix 95. Pt-RNA adducts occur
      on the nucleotide substrates of ribosome-inactivating proteins, as well as on the
      bulged-G motif critical for elongation factor recognition of the loop. At
      therapeutically relevant concentrations, Pt(II) also binds robustly within
      conserved cation-binding pockets in Domains V and VI rRNA at the peptidyl
      transferase center. Taken together, these results demonstrate a convenient click
      chemistry methodology that can be applied to identify other metal or covalent
      modification-based drug targets and suggest a ribotoxic mechanism for cisplatin
      cytotoxicity. 

PMID- 25055169
TI  - Cannabis use and transition to psychosis in people at ultra-high risk.
AB  - BACKGROUND: Cannabis use is associated with an increased risk of developing a
      psychotic disorder but the temporal relationship between cannabis use and onset
      of illness is unclear. The objective of this study was to assess prospectively
      the influence of cannabis use on transition to psychosis in people at ultra-high
      risk (UHR) for the disorder. METHOD: Lifetime and continued cannabis use was
      assessed in a consecutively ascertained sample of 182 people (104 male, 78
      female) at UHR for psychosis. Individuals were then followed clinically for 2
      years to determine their clinical outcomes. RESULTS: Lifetime cannabis use was
      reported by 134 individuals (73.6%). However, most of these individuals had
      stopped using cannabis before clinical presentation (n=98, 73.1%), usually
      because of adverse effects. Among lifetime users, frequent use, early-onset use
      and continued use after presentation were all associated with an increase in
      transition to psychosis. Transition to psychosis was highest among those who
      started using cannabis before the age of 15 years and went on to use frequently
      (frequent early-onset use: 25%; infrequent or late-onset use: 5%; chi(2)1=10.971,
      p=0.001). However, within the whole sample, cannabis users were no more likely to
      develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no
      use: 18.8%; chi(2)1=1.061, p=0.303). CONCLUSIONS: In people at UHR for psychosis,
      lifetime cannabis use was common but not related to outcome. Among cannabis
      users, frequent use, early-onset use and continued use after clinical
      presentation were associated with transition to psychosis.

PMID- 25055170
TI  - Prognosis of schizophrenia in persons with and without a history of cannabis use.
AB  - BACKGROUND: The aim of the study was to determinate whether schizophrenia
      patients with a history of cannabis use have a different prognosis, with regards
      to readmission and hospital duration, compared with those without a history of
      cannabis use. METHOD: The present investigation was a cohort study of 50,087
      Swedish men with data on cannabis use at the ages of 18-20 years. A total of 357
      cases of schizophrenia were identified from in-patient care and followed up from
      1973 to 2007. RESULTS: Schizophrenia patients with a history of cannabis use had
      a higher median duration of first hospital episode (59 days v. 30 days). Patients
      with a history of cannabis use had a higher median rate of readmission (10 times
      v. four times). Also, total number of hospital days was higher in patients with a
      history of cannabis use compared with those without (547 days v. 184 days).
      Patients with a history of cannabis use had an increased odds of having more than
      20 hospital readmissions compared with non-users [3.1, 95% confidence interval
      (CI) 1.3-7.3] as well as an increased odds of hospital admission lasting more
      than 2 years (2.4, 95% CI 1.1-7.4) after controlling for diagnosis of personality
      disorders, family socio-economic position, IQ score, civil status, place of
      residence, risky use of alcohol and use of other drugs. Patients with a history
      of cannabis use were less likely to have paranoid schizophrenia compared with
      never users (8% v. 17%) in the first admission. CONCLUSIONS: Schizophrenia
      patients with a history of cannabis use had a significantly higher burden of
      lifetime in-patient care than non-cannabis users. Not only does cannabis increase
      the risk of schizophrenia, but also our findings indicate that the course and
      prognosis of schizophrenia may be more severe than schizophrenia cases in
      general.

PMID- 25055172
TI  - The causal nature of the association between neighborhood deprivation and drug
      abuse: a prospective national Swedish co-relative control study.
AB  - BACKGROUND: Risk for drug abuse (DA) is strongly associated with neighborhood
      social deprivation (SD). However, the causal nature of this relationship is
      unclear. METHOD: Three Swedish population-based cohorts were followed up over 5
      years for incident registration of DA in medical, legal or pharmacy records. In
      each cohort, we examined the SD-DA association, controlling carefully for
      individual socio-economic status (SES) with multiple measures, in the entire
      sample and among pairs of first cousins, paternal and maternal half-siblings,
      full siblings and monozygotic (MZ) twins discordant for SD exposure. The number
      of informative relative pairs ranged from 6366 to 166,208. RESULTS: In all
      cohorts, SD was prospectively related to risk for incident DA. In relative pairs
      discordant for SD exposure, the SD-DA association was similar to that seen in the
      entire population in cousins, half-siblings, full siblings and MZ twins.
      Eliminating subjects who were residentially unstable or had DA in the first two
      follow-up years did not alter this pattern. When divided by age, in the youngest
      groups, the SD-DA association was weaker in siblings than in the entire
      population. CONCLUSIONS: Across three cohorts, controlling for individual SES and
      confounding familial factors, SD prospectively predicted risk for incident DA
      registration. These results support the hypothesis that the SD-DA association is
      in part causal and unlikely to result entirely from personal attributes, which
      both increase risk for DA and cause selection into high SD environments. At least
      part of the SD-DA association arises because exposure to SD causes an increased
      risk of DA.

PMID- 25055171
TI  - Smoking cessation is associated with lower rates of mood/anxiety and alcohol use
      disorders.
AB  - BACKGROUND: The psychological outcomes that accompany smoking cessation are not
      yet conclusive but positive outcomes could help to persuade quitting. METHOD: We
      used data from the longitudinal National Epidemiological Study of Alcohol and
      Related Conditions. Logistic regression was used to examine associations between
      cigarette smoking reduction and Wave 2 status of addiction/mental health disorder
      among daily smokers at Wave 1, stratified by status of the diagnosis of interest
      at Wave 1. We adjusted for differences in baseline covariates between smokers
      with different levels of smoking reduction between Wave 1 and Wave 2 using
      propensity score regression adjustment. RESULTS: After adjusting for propensity
      scores and other mental health/addiction co-morbidities at Wave 2, among daily
      smokers who had current or lifetime history diagnosis of the outcome of interest
      at Wave 1, quitting by Wave 2 predicted a decreased risk of mood/anxiety disorder
      [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.4-0.9] and alcohol
      disorder (aOR 0.7, 95% CI 0.5-0.99) at Wave 2. Among daily smokers with no
      lifetime history diagnosis of the outcome of interest at Wave 1, quitting smoking
      by Wave 2 predicted a decreased risk of drug use disorder at Wave 2 (aOR 0.3, 95%
      CI 0.1-0.9). CONCLUSIONS: There is no support in our data for the concern that
      smoking cessation would result in smokers' increased risk of some mental
      disorders. To the contrary, our data suggest that smoking cessation is associated
      with risk reduction for mood/anxiety or alcohol use disorder, even among smokers
      who have had a pre-existing disorder.

PMID- 25055174
TI  - A symptom profile of depression among Asian Americans: is there evidence for
      differential item functioning of depressive symptoms?
AB  - BACKGROUND: Theoretical and clinical publications suggest the existence of
      cultural differences in the expression and experience of depression. Measurement
      non-equivalence remains a potential methodological explanation for the lower
      prevalence of depression among Asian Americans compared to European Americans.
      METHOD: This study compared DSM-IV depressive symptoms among Asian Americans and
      European Americans using secondary data analysis of the Collaborative Psychiatric
      Epidemiology Surveys (CPES). The Composite International Diagnostic Interview
      (CIDI) was used for the assessment of depressive symptoms. Of the entire sample,
      310 Asian Americans and 1974 European Americans reported depressive symptoms and
      were included in the analyses. Measurement variance was examined with an item
      response theory differential item functioning (IRT DIF) analysis. RESULTS: chi2
      analyses indicated that, compared to Asian Americans, European American
      participants more frequently endorsed affective symptoms such as 'feeling
      depressed', 'feeling discouraged' and 'cried more often'. The IRT analysis
      detected DIF for four out of the 15 depression symptom items. At equal levels of
      depression, Asian Americans endorsed feeling worthless and appetite changes more
      easily than European Americans, and European Americans endorsed feeling nervous
      and crying more often than Asian Americans. CONCLUSIONS: Asian Americans did not
      seem to over-report somatic symptoms; however, European Americans seemed to
      report more affective symptoms than Asian Americans. The results suggest that
      there was measurement variance in a few of the depression items.

PMID- 25055173
TI  - Common versus psychopathology-specific risk factors for psychotic experiences and
      depression during adolescence.
AB  - BACKGROUND: An argument often used to support the view that psychotic experiences
      (PEs) in general population samples are a valid phenotype for studying the
      aetiology of schizophrenia is that risk factors for schizophrenia show similar
      patterns of association with PEs. However, PEs often co-occur with depression,
      and no study has explicitly tested whether risk factors for schizophrenia are
      shared between PEs and depression, or are psychopathology specific, while jointly
      modelling both outcomes. METHOD: We used data from 7030 subjects from a birth
      cohort study. Depression and PEs at age 18 years were assessed using self-report
      questionnaires and semi-structured interviews. We compared the extent to which
      risk factors for schizophrenia across sociodemographic, familial,
      neurodevelopmental, stress-adversity, emotional-behavioural and substance use
      domains showed different associations with PEs and depression within bivariate
      models that allowed for their correlation. RESULTS: Most of the exposures
      examined were associated, to a similar degree, with an increased risk of both
      outcomes. However, whereas female sex and family history of depression showed
      some discrimination as potential risk factors for depression and PEs, with
      stronger associations in the former, markers of abnormal neurodevelopment showed
      stronger associations with PEs. CONCLUSIONS: The argument that PEs are valid
      markers for studying the aetiology of schizophrenia, made simply on the basis
      that they share risk factors in common, is not well supported. PEs seem to be a
      weak index of genetic and environmental risk for schizophrenia; however, studies
      disentangling aetiological pathways to PEs from those impacting upon co-morbid
      psychopathology might provide important insights into the aetiology of psychotic
      disorders.

PMID- 25055176
TI  - Personality change associated with chronic diseases: pooled analysis of four
      prospective cohort studies.
AB  - BACKGROUND: Common chronic conditions, such as heart disease and cancer, are
      associated with increased psychological distress, functional limitations and
      shortened life expectancy, but whether these diseases alter aspects of
      personality remains unclear. METHOD: To examine whether the onset of heart
      disease, stroke, diabetes, cancer, hypertension, arthritis and respiratory
      disease is associated with subsequent changes in personality traits of the five
      factor model, we pooled data from the Health and Retirement Study, the Midlife in
      the United States Survey, and the graduate and sibling samples of the Wisconsin
      Longitudinal Study for an individual-participant meta-analysis (total n=17,493;
      mean age at baseline 55.8 years). RESULTS: After adjustment for age, we observed
      consistent decreases in extraversion [-0.25 T-scores per one disease; 95%
      confidence interval (CI) -0.40 to -0.10], emotional stability (-0.40, 95% CI 
      0.61 to -0.19), conscientiousness (-0.44, 95% CI -0.57 to -0.30) and openness to
      experience (-0.25, 95% CI -0.37 to -0.13) but not in agreeableness (-0.05, 95% CI
      -0.19 to 0.08) after the onset of chronic diseases. The onset of each additional
      chronic disease accelerated the average age-related personality change by 2.5
      years in decreasing extraversion, 5.5 years in decreasing conscientiousness, and
      1.6 years in decreasing openness to experience, and attenuated the increasing
      levels of emotional stability by 1.9 years. Co-morbid conditions were associated
      with larger changes than single diseases, suggesting a dose-response association
      between morbidity and personality change. CONCLUSIONS: These results support the
      hypothesis that chronic diseases influence personality development in adulthood.

PMID- 25055177
TI  - Depressive symptoms and body mass index: co-morbidity and direction of
      association in a British birth cohort followed over 50 years.
AB  - BACKGROUND: An unhealthy body mass index (BMI) has been associated with
      depression but the direction of association is uncertain. Our aim was to estimate
      the co-morbidity and direction of association between BMI and depressive symptoms
      at several ages, from childhood to mid-adulthood. METHOD: The data were from
      18,558 individuals born in 1 week in March 1958, in England, Scotland and Wales,
      with follow-up at ages 7, 11, 16, 23, 33, 42, 45 and 50 years. Depression
      (scores>or=90th percentile) was identified from child/adolescent (teacher
      questionnaires) and adult (self-complete questionnaires and clinical interview)
      measures. BMI (kg/m2) measured in child/adolescence and adulthood was classified
      as underweight, normal, overweight or obese. RESULTS: In cross-sectional
      analyses, obesity and underweight (not overweight) from 11 to 45 years were
      associated respectively with 1.3-2.1 and 1.5-2.3 times the risk of depression
      compared with normal weight. Using the time-lagged generalized estimating
      equation (GEE) approach, we tested (a) whether underweight or obesity at prior
      ages (7 to 45 years) predicted subsequent risk of depression (11 to 50 years),
      adjusting for baseline depression; and (b) whether depression at prior ages (7 to
      42 years) predicted subsequent risk of underweight or obesity (11 to 45 years),
      adjusting for baseline BMI. In longitudinal analyses, underweight predicted
      subsequent depression in both sexes [odds ratio (OR) 1.25, 95% confidence
      interval (CI) 1.11-1.40] and depression predicted subsequent underweight in males
      only (OR 1.84, 95% CI 1.52-2.23). Obesity predicted subsequent depressive
      symptoms in females only (OR 1.34, 95% CI 1.14-1.56), but depression did not
      predict obesity. CONCLUSIONS: Clinicians should consider screening routinely for
      depression patients with unhealthy BMI, namely underweight and obesity, and vice
      versa.

PMID- 25055175
TI  - Sociodemographic and career history predictors of suicide mortality in the United
      States Army 2004-2009.
AB  - BACKGROUND: The US Army suicide rate has increased sharply in recent years.
      Identifying significant predictors of Army suicides in Army and Department of
      Defense (DoD) administrative records might help focus prevention efforts and
      guide intervention content. Previous studies of administrative data, although
      documenting significant predictors, were based on limited samples and models. A
      career history perspective is used here to develop more textured models. METHOD:
      The analysis was carried out as part of the Historical Administrative Data Study
      (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army
      STARRS). De-identified data were combined across numerous Army and DoD
      administrative data systems for all Regular Army soldiers on active duty in 2004
      2009. Multivariate associations of sociodemographics and Army career variables
      with suicide were examined in subgroups defined by time in service, rank and
      deployment history. RESULTS: Several novel results were found that could have
      intervention implications. The most notable of these were significantly elevated
      suicide rates (69.6-80.0 suicides per 100 000 person-years compared with 18.5
      suicides per 100 000 person-years in the total Army) among enlisted soldiers
      deployed either during their first year of service or with less than expected
      (based on time in service) junior enlisted rank; a substantially greater rise in
      suicide among women than men during deployment; and a protective effect of
      marriage against suicide only during deployment. CONCLUSIONS: A career history
      approach produces several actionable insights missed in less textured analyses of
      administrative data predictors. Expansion of analyses to a richer set of
      predictors might help refine understanding of intervention implications.

PMID- 25055178
TI  - Cortisol awakening response in patients with anorexia nervosa or bulimia nervosa:
      relationships to sensitivity to reward and sensitivity to punishment.
AB  - BACKGROUND: Sensitivity to punishment (SP) and sensitivity to reward (SR) are
      personality characteristics that may have relevance for the pathophysiology of
      eating disorders (EDs). Moreover, personality characteristics are known to
      modulate the activity of the hypothalamus-pituitary-adrenal (HPA) axis, which is
      the main component of the endogenous stress response system. As stress has been
      implicated in the aetiology and the maintenance of EDs, we aimed to study the HPA
      axis activity in relation to SP and SR, as conceptualized by Gray's reinforcement
      sensitivity theory (RST), in patients with anorexia nervosa (AN) or bulimia
      nervosa (BN). METHOD: Twenty-five women with AN, 23 women with BN and 19 healthy
      women volunteered for the study. HPA axis activity was assessed by measurement of
      the salivary cortisol awakening response (CAR). The subjects' SP and SR were
      measured by the behavioural inhibition system (BIS)/behavioural approach system
      (BAS) scales. RESULTS: The CAR was significantly enhanced in AN patients, but not
      in BN patients, compared to healthy women. The CAR correlated significantly with
      BAS measures, negatively in healthy controls and positively in binge-purging AN
      patients and BN women. SP, measured by the BIS scale, was higher in patients than
      in controls. CONCLUSIONS: These findings confirm the occurrence of an enhanced
      activity of the HPA axis in symptomatic AN, but not in symptomatic BN, and show
      for the first time that the CAR is associated with SR, as conceptualized by the
      RST, negatively in healthy subjects but positively in binge-purging ED patients.

PMID- 25055180
TI  - Highly regioselective nickel-catalyzed cross-coupling of N-tosylaziridines and
      alkylzinc reagents.
AB  - Herein, we report the first ligand-controlled, nickel-catalyzed cross-coupling of
      aliphatic N-tosylaziridines with aliphatic organozinc reagents. The reaction
      protocol displays complete regioselectivity for reaction at the less hindered C-N
      bond, and the products are furnished in good to excellent yield for a broad
      selection of substrates. Moreover, we have developed an air-stable nickel(II)
      chloride/ligand precatalyst that can be handled and stored outside a glovebox. In
      addition to increasing the activity of this catalyst system, this also greatly
      improves the practicality of this reaction, as the use of the very air-sensitive
      Ni(cod)2 is avoided. Finally, mechanistic investigations, including deuterium
      labeling studies, show that the reaction proceeds with overall inversion of
      configuration at the terminal position of the aziridine by way of aziridine ring
      opening by Ni (inversion), transmetalation (retention), and reductive elimination
      (retention). 

PMID- 25055181
TI  - Physical origins and suppression of Ag dissolution in GeS(x)-based ECM cells.
AB  - Electrochemical metallisation (ECM) memory cells potentially suffer from limited
      memory retention time, which slows down the future commercialisation of this type
      of data memory. In this work, we investigate Ag/GeSx/Pt redox-based resistive
      memory cells (ReRAM) with and without an additional Ta barrier layer by time-of
      flight secondary ion mass spectrometry (ToF-SIMS), X-ray absorption spectroscopy
      (XAS) and synchrotron high-energy X-ray diffractometry (XRD) to investigate the
      physical mechanism behind the shift and/or loss of OFF data retention. Electrical
      measurements demonstrate the effectiveness and high potential of the diffusion
      barrier layer in practical applications. 

PMID- 25055179
TI  - Action-value comparisons in the dorsolateral prefrontal cortex control choice
      between goal-directed actions.
AB  - It is generally assumed that choice between different actions reflects the
      difference between their action values yet little direct evidence confirming this
      assumption has been reported. Here we assess whether the brain calculates the
      absolute difference between action values or their relative advantage, that is,
      the probability that one action is better than the other alternatives. We use a
      two-armed bandit task during functional magnetic resonance imaging and modelled
      responses to determine both the size of the difference between action values (D)
      and the probability that one action value is better (P). The results show
      haemodynamic signals corresponding to P in right dorsolateral prefrontal cortex
      (dlPFC) together with evidence that these signals modulate motor cortex activity
      in an action-specific manner. We find no significant activity related to D. These
      findings demonstrate that a distinct neuronal population mediates action-value
      comparisons, and reveals how these comparisons are implemented to mediate value
      based decision-making. 

PMID- 25055182
TI  - Visfatin derived from ascites promotes ovarian cancer cell migration through
      Rho/ROCK signaling-mediated actin polymerization.
AB  - Ovarian cancer is characterized by a rapid intraperitoneal spread combination
      with ascites accumulation. However, the exact mechanisms for ovarian cancer
      intraperitoneal dissemination remain unknown. Visfatin has recently been
      established as a novel adipokine and its serum level is increased in various
      cancers. Here, we identified that the elevated level of visfatin in ascites was
      associated with ovarian cancer intraperitoneal dissemination. Using the transwell
      cell migration assay and the wound-healing assay, we found that ascites-derived
      visfatin could promote migration of Caov-3 cells. Meanwhile, visfatin could
      induce the aggregation of actin stress fibers and the formation of lamellipodia
      and filopodia in Caov-3 cells, concomitant with a shift of G-actin to F-actin.
      Inhibition of actin polymerization with cytochalasin D obviously abolished the
      effects of visfatin on the migration of Caov-3 cells. Further results showed that
      visfatin triggered Rho activation and its downstream cofilin phosphorylation in a
      time-dependent manner, which led to actin polymerization. More importantly,
      visfatin-induced Caov-3 cell migration was effectively blocked by C3 exoenzyme
      and Y27632, Rho, and ROCK inhibitor, respectively. Thus, our study showed that
      ascites-derived visfatin promoted migration of ovarian cancer cells through
      Rho/ROCK signaling-mediated actin polymerization, which was required for ovarian
      cancer intraperitoneal dissemination. These findings offered a novel molecular
      mechanism responsible for ovarian cancer intraperitoneal dissemination, which
      might be a potential target for ovarian cancer management. 

PMID- 25055183
TI  - Pharmacological evidence of alpha2-adrenergic receptors in the hypotensive effect
      of Platonia insignis mart.
AB  - Platonia insignis Mart. (Clusiaceae) is a medicinal plant from the Brazilian
      Amazon region. The present study evaluated the biological potential of the
      ethanol extract (Pi-EtOH) and ethyl acetate fraction (Pi-EtOAc) of the P.
      insignis fruit shells on the cardiovascular system of rats. Pi-EtOH or Pi-EtOAc
      (12.5, 25, and 50 mg/kg) was administered intravenously in normotensive rats (260
      300 g), and the mean arterial pressure and the heart rate were monitored. The Pi
      EtOH induced hypotension (-11.56+/-0.89, -7.43+/-0.85, and -17.56+/-1.97 mmHg)
      followed by bradycardia in two highest doses (-8.89+/-3.62 and -15.79+/-1.83
      beats/min) and Pi-EtOAc, at the same doses, induced hypotension (-11.2+/-1.03, 
      14.48+/-1.13, -29.89+/-2.67 mmHg) more intensively, followed by tachycardia at
      the dose 12.5 and 25 mg/kg (15.64+/-2.06, 19.31+/-1.92 beats/min) and bradycardia
      at a dose of 50 mg/kg (-9.98+/-7.33 beats/min). The hypotensive response from Pi
      EtOAc was not attenuated when used in the pretreatment with L-NAME, verapamil,
      propranolol, and hexamethonium. However, when using yohimbine, the hypotensive
      effect was inhibited (-4.42+/-1.28 (P<.05), -3.29+/-0.99 (P<.05), 2.06+/-1.18
      mmHg (P<.05); Student's t-test). Hence, the Pi-EtOAc seems to act similarly to
      the alpha2-adrenergic agonist in this hypotensive effect.

PMID- 25055184
TI  - Progress toward prevention of transfusion-transmitted hepatitis B and hepatitis C
      infection--sub-Saharan Africa, 2000-2011.
AB  - Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are major
      causes of morbidity and mortality globally, primarily because of sequelae of
      chronic liver disease including cirrhosis and hepatocellular carcinoma. The risks
      for HBV and HCV transmission via blood transfusions have been described
      previously and are believed to be higher in countries in sub-Saharan Africa.
      Reducing the risk for transfusion-transmitted human immunodeficiency virus (HIV),
      HBV, and HCV infection is a priority for international aid organizations, such as
      the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund to
      Combat HIV/AIDS, Malaria, and Tuberculosis, and the World Health Organization
      (WHO). Over the last decade, PEPFAR and the Global Fund have supported blood
      safety programs in many sub-Saharan African countries with heavy burdens of HIV
      and acquired immunodeficiency syndrome (AIDS), hepatitis, malaria, and maternal
      mortality. This report summarizes HBV- and HCV-related surveillance data reported
      by the blood transfusion services of WHO member states to WHO's Global Database
      on Blood Safety (GDBS) (4). It also evaluates the performance of blood safety
      programs in screening for HBV and HCV in 38 sub-Saharan Africa countries.
      Selected GDBS indicators were compared for the years 2000 and 2004 (referred to
      as the 2000/2004 period) and 2010 and 2011 (referred to as the 2010/2011 period).
      From 2000/2004 to 2010/2011, the median of the annual number of units donated per
      country increased, the number of countries screening at least 95% of blood
      donations for HBV and HCV increased, and the median of the national prevalence of
      HBV and HCV marker-reactive blood donations decreased. These findings suggest
      that during the past decade, more blood has been donated and screened for HBV and
      HCV, resulting in a safer blood supply. Investments in blood safety should be
      continued to further increase the availability and safety of blood products in
      sub-Saharan Africa.

PMID- 25055185
TI  - Human papillomavirus vaccination coverage among adolescents, 2007-2013, and
      postlicensure vaccine safety monitoring, 2006-2014--United States.
AB  - Since mid-2006, a licensed human papillomavirus (HPV) vaccine has been available
      and recommended by the Advisory Committee on Immunization Practices (ACIP) for
      routine vaccination of adolescent girls at ages 11 or 12 years. Two vaccines that
      protect against HPV infection are currently available in the United States. Both
      the quadrivalent (HPV4) and bivalent (HPV2) vaccines protect against HPV types 16
      and 18, which cause 70% of cervical cancers; HPV4 also protects against HPV types
      6 and 11, which cause 90% of genital warts. In 2011, the ACIP also recommended
      HPV4 for the routine vaccination of adolescent boys at ages 11 or 12 years. HPV
      vaccines can be safely co-administered with other routinely recommended vaccines,
      and ACIP recommends administration of all age-appropriate vaccines during a
      single visit. To assess progress with HPV vaccination coverage among adolescents
      aged 13-17 years, characterize adherence with recommendations for HPV vaccination
      by the 13th birthday, and describe HPV vaccine adverse reports received
      postlicensure, CDC analyzed data from the 2007-2013 National Immunization Survey
      Teen (NIS-Teen) and national postlicensure vaccine safety data among females and
      males. Vaccination coverage with >=1 dose of any HPV vaccine increased
      significantly from 53.8% (2012) to 57.3% (2013) among adolescent girls and from
      20.8% (2012) to 34.6% (2013) among adolescent boys. Receipt of >=1 dose of HPV
      among girls by age 13 years increased with each birth cohort; however, missed
      vaccination opportunities were common. Had HPV vaccine been administered to
      adolescent girls born in 2000 during health care visits when they received
      another vaccine, vaccination coverage for >=1 dose by age 13 years for this
      cohort could have reached 91.3%. Postlicensure monitoring data continue to
      indicate that HPV4 is safe. Improving practice patterns so that clinicians use
      every opportunity to recommend HPV vaccines and address questions from parents
      can help realize reductions in vaccine-preventable infections and cancers caused
      by HPV.

PMID- 25055186
TI  - National, regional, state, and selected local area vaccination coverage among
      adolescents aged 13-17 years--United States, 2013.
AB  - The Advisory Committee on Immunization Practices (ACIP) recommends that
      adolescents routinely receive 1 dose of tetanus toxoid, reduced diphtheria
      toxoid, and acellular pertussis (Tdap) vaccine, 2 doses of meningococcal
      conjugate (MenACWY) vaccine, and 3 doses of human papillomavirus (HPV) vaccine.*
      ACIP also recommends administration of "catch-up"? vaccinations, such as measles,
      mumps, and rubella (MMR), hepatitis B, and varicella, and, for all persons aged
      >=6 months, an annual influenza vaccination. ACIP recommends administration of
      all age-appropriate vaccines during a single visit. To assess vaccination
      coverage among adolescents aged 13-17 years, CDC analyzed data from the 2013
      National Immunization Survey-Teen (NIS-Teen).S This report summarizes the results
      of that analysis, which show that from 2012 to 2013, coverage increased for each
      of the vaccines routinely recommended for adolescents: from 84.6% to 86.0% for
      >=1 Tdap dose; from 74.0% to 77.8% for >=1 MenACWY dose; from 53.8% to 57.3% for
      >=1 HPV dose among females, and from 20.8% to 34.6% for >=1 HPV dose among males.
      Coverage varied by state and local jurisdictions and by U.S. Department of Health
      and Human Services (HHS) region. Healthy People 2020 vaccination targets for
      adolescents aged 13-15 years were reached in 42 states for >=1 Tdap dose, 18 for
      >=1 MenACWY dose, and 11 for >=2 varicella doses. No state met the target for >=3
      HPV doses.  Use of patient reminder and recall systems, immunization information
      systems, coverage assessment and feedback to clinicians, clinician reminders,
      standing orders, and other interventions can help make use of every health care
      visit to ensure that adolescents are fully protected from vaccine-preventable
      infections and cancers (5), especially when such interventions are coupled with
      clinicians' vaccination recommendations. 

PMID- 25055187
TI  - WHO global rotavirus surveillance network: a strategic review of the first 5
      years, 2008-2012.
AB  - Since 2008, the World Health Organization (WHO) has coordinated the Global
      Rotavirus Surveillance Network, a network of sentinel surveillance hospitals and
      laboratories that report to ministries of health (MoHs) and WHO clinical features
      and rotavirus testing data for children aged <5 years hospitalized with acute
      gastroenteritis. In 2013, WHO conducted a strategic review to assess surveillance
      network performance, provide recommendations for strengthening the network, and
      assess the network's utility as a platform for other vaccine-preventable disease
      surveillance. The strategic review team determined that during 2011 and 2012, a
      total of 79 sites in 37 countries met reporting and testing inclusion criteria
      for data analysis. Of the 37 countries with sites meeting inclusion criteria, 13
      (35%) had introduced rotavirus vaccine nationwide. All 79 sites included in the
      analysis were meeting 2008 network objectives of documenting presence of disease
      and describing disease epidemiology, and all countries were using the rotavirus
      surveillance data for vaccine introduction decisions, disease burden estimates,
      and advocacy; countries were in the process of assessing the use of this
      surveillance platform for other vaccine-preventable diseases. However, the review
      also indicated that the network would benefit from enhanced management,
      standardized data formats, linkage of clinical data with laboratory data, and
      additional resources to support network functions. In November 2013, WHO's
      Strategic Advisory Group of Experts on Immunization (SAGE) endorsed the findings
      and recommendations made by the review team and noted potential opportunities for
      using the network as a platform for other vaccine-preventable disease
      surveillance. WHO will work to implement the recommendations to improve the
      network's functions and to provide higher quality surveillance data for use in
      decisions related to vaccine introduction and vaccination program sustainability.

PMID- 25055188
TI  - Nutritional status of women and child refugees from Syria-Jordan, April-May 2014.
AB  - As a result of civil war, an estimated 2.8 million refugees have fled Syria and
      reside in neighboring countries, mainly Lebanon, Turkey, Jordan, and Iraq. The
      largest Syrian refugee camp in the region is Zaatari camp in Jordan, with
      approximately 79,000 refugees; another estimated 500,000 Syrian refugees live in
      Jordanian cities, towns, and villages, mostly in the capital (Amman) and in four
      northern governorates (Irbid, Mafraq, Jarash, and Zarqa). Although all registered
      refugees in Jordan receive food vouchers from the World Food Programme (WFP) and
      vulnerable refugees receive cash assistance from the United Nations High
      Commissioner for Refugees (UNHCR) and nongovernmental organizations, the
      nutritional status of some refugees might be compromised because of dislocation,
      lack of income, and limited access to nutritious foods. To assess the nutritional
      status of Syrian refugees, UNHCR, WFP, the United Nations Children's Fund
      (UNICEF), Medair International (a nongovernmental organization), and CDC, in
      collaboration with the United Nations Population Fund and the World Health
      Organization (WHO), conducted cross-sectional, population-representative cluster
      surveys in Zaatari camp and among refugees residing in the host community. The
      surveys were conducted during April-May 2014 with the principal objective of
      assessing nutritional status of refugee children aged 6-59 months and nonpregnant
      women of reproductive age (15-49 years). Preliminary findings indicated a high
      prevalence of anemia in Zaatari camp among both children and women (48.4% and
      44.8%, respectively). Nutrition policies aimed at ensuring optimal child and
      maternal micronutrient status and addressing the underlying risk factors for
      anemia are likely to result in improved health outcomes and a reduction in
      anemia. 

PMID- 25055189
TI  - Mathematical modeling of HIV dynamics after antiretroviral therapy initiation: a
      clinical research study.

PMID- 25055190
TI  - Inter- and intraspecies transfer of a Clostridium difficile conjugative
      transposon conferring resistance to MLSB.
AB  - Resistance to the macrolide-lincosamide-streptogramin B group of antibiotics in
      Clostridium difficile is generally due to erm(B) genes. Tn6194, a conjugative
      transposon initially detected in PCR-ribotype 027 isolates, is an erm(B)
      containing element also detected in other relevant C. difficile PCR-ribotypes. In
      this study, the genome of a C. difficile PCR-ribotype 001 strain was sequenced,
      and an element with two nucleotidic changes compared to Tn6194 was detected. This
      element was transferred by filter mating assays to recipient strains of C.
      difficile belonging to PCR-ribotype 009 and 027 and to a recipient strain of
      Enterococcus faecalis. Transconjugants were characterized by Southern blotting
      and genome sequencing, and integration sites in all transconjugants were
      identified. The element integrated the genome of C. difficile at different sites
      and the genome of E. faecalis at a unique site. This study is the first molecular
      characterization of an erm(B)-containing conjugative transposon in C. difficile
      and provides additional evidence of the antibiotic resistance transmission risk
      among pathogenic bacteria occupying the same human intestinal niche. 

PMID- 25055191
TI  - Reaching low density lipoprotein cholesterol targets.
AB  - Cardiovascular disease is a major health problem and within the leading causes of
      death worldwide. Low-density lipoprotein cholesterol (LDL-C) is strongly
      associated with the development and progression of cardiovascular disease and is
      among the main targets of lipid lowering therapy. Despite the various lipid
      lowering agents for the management of hyperlipidemia, a significant number of
      patients do not reach their LDL-C target goals. Data from studies in various
      world regions identify an often poor achievement of LDL-C goals, especially in
      high risk patient groups. The causes of this suboptimal management of
      hyperlipidemia are multifactorial and measures should be taken in order to
      identify and address these shortcomings in dyslipidemia therapy.

PMID- 25055192
TI  - Continuous recycling of homogeneous Pd/Cu catalysts for cross-coupling reactions.
AB  - Given the importance of homogeneous catalysts recycling in organic chemistry, we
      have developed a unique microfluidic loop system for automated continuous
      recirculation of a soluble polymer supported metal catalyst for novel isocyanide
      cross-coupling reactions under thermomorphic multicomponent solvent (TMS)
      conditions. Our system provides an innovative approach for the chemical library
      synthesis of quinazolinone derivatives as well as an important intermediate of
      Merck's LTD4 antagonist "Singulair" with efficient continuous homogeneous
      catalyst recycling. 

PMID- 25055193
TI  - Derivation of mesenchymal stromal cells from canine induced pluripotent stem
      cells by inhibition of the TGFbeta/activin signaling pathway.
AB  - In this study we have generated canine mesenchymal stromal cells (MSCs), also
      known as mesenchymal stem cells, from canine induced pluripotent stem cells
      (ciPSCs) by small-molecule inhibition of the transforming growth factor beta
      (TGFbeta)/activin signaling pathway. These ciPSC-derived MSCs (ciPSC-MSCs)
      express the MSC markers CD73, CD90, CD105, STRO1, cPDGFRbeta and cKDR, in
      addition to the pluripotency factors OCT4, NANOG and REX1. ciPSC-MSCs lack
      immunostaining for H3K27me3, suggesting that they possess two active X
      chromosomes. ciPSC-MSCs are highly proliferative and undergo robust
      differentiation along the osteo-, chondro- and adipogenic pathways, but do not
      form teratoma-like tissues in vitro. Of further significance for the
      translational potential of ciPSC-MSCs, we show that these cells can be
      encapsulated and maintained within injectable hydrogel matrices that, when
      functionalized with bound pentosan polysulfate, dramatically enhance
      chondrogenesis and inhibit osteogenesis. The ability to efficiently derive large
      numbers of highly proliferative canine MSCs from ciPSCs that can be incorporated
      into injectable, functionalized hydrogels that enhance their differentiation
      along a desired lineage constitutes an important milestone towards developing an
      effective MSC-based therapy for osteoarthritis in dogs, but equally provides a
      model system for assessing the efficacy and safety of analogous approaches for
      treating human degenerative joint diseases. 

PMID- 25055194
TI  - Association of pain and itch with depth of invasion and inflammatory cell
      constitution in skin cancer: results of a large clinicopathologic study.
AB  - IMPORTANCE: This study highlights a simple bedside evaluation of itch and pain
      for suspicious skin lesions. OBJECTIVE: To examine the correlation of pain and
      itch with histologic features of skin cancers. DESIGN, SETTING, AND PARTICIPANTS:
      This large, prospective, clinicopathologic study enrolled patients who filled out
      questionnaires that assessed itch and pain intensity of their skin tumors at the
      time of excision. Study participants were from the patient population presenting
      to the Department of Dermatology surgical unit at Wake Forest University Baptist
      Medical Center from July 1, 2010, through March 31, 2011. Study participants
      included 268 patients, representing 339 histopathologically confirmed cutaneous
      neoplasms. The following skin cancer subtypes were represented in this analysis:
      166 basal cell carcinomas, 146 squamous cell carcinomas, and 27 melanomas. MAIN
      OUTCOMES AND MEASURES: Itch and pain associated with skin cancer at the time of
      excision ranked on an 11-point (score range, 0-10) numerical visual analog scale
      and histopathologic analysis for each neoplasm (assessment of the amount and type
      of inflammation, ulceration, perineural invasion, and depth of invasion).
      RESULTS: The prevalence of itch and pain across all skin cancers was 36.9% and
      28.2%, respectively. However, these symptoms were mostly absent in melanomas.
      Pain intensity was significantly associated with the degree of inflammation (mild
      or none vs moderate or marked; P < .001), presence of neutrophils in the
      inflammatory infiltrate (predominantly mononuclear vs mixed or neutrophilic; P =
      .003), presence of eosinophils (present vs absent; P = .007), ulceration (yes vs
      no; P = .003), perineural invasion (yes vs no; P < .001), depth of invasion (P =
      .001), and largest diameter length of skin lesion (P < .003). Itch intensity was
      significantly associated with the degree of inflammation (mild or none vs
      moderate or marked; P = .001) and the presence of eosinophils (present vs absent;
      P = .02). CONCLUSIONS AND RELEVANCE: These findings support the theory that itch
      emanates from the upper layers of the skin, whereas pain is associated with
      deeper processes. This study also reports that a simple bedside assessment for
      the presence and intensity of pain or itch is an easily implementable tool for
      physicians evaluating suspicious skin lesions.

PMID- 25055195
TI  - A single nucleotide polymorphism in the corticotropin receptor gene is associated
      with a blunted cortisol response during pediatric critical illness.
AB  - OBJECTIVES: The cortisol response during critical illness varies widely among
      patients. Our objective was to examine single nucleotide polymorphisms in
      candidate genes regulating cortisol synthesis, metabolism, and activity to
      determine if genetic differences were associated with variability in the cortisol
      response among critically ill children. DESIGN: This was a prospective
      observational study employing tag single nucleotide polymorphism methodology to
      examine genetic contributions to the variability of the cortisol response in
      critical illness. Thirty-one candidate genes and 31 ancestry markers were
      examined. SETTING: Patients were enrolled from seven pediatric critical care
      units that constitute the Eunice Kennedy Shriver Collaborative Pediatric Critical
      Care Research Network. SUBJECTS: Critically ill children (n = 92), age 40 weeks
      gestation to 18 years old, were enrolled. INTERVENTIONS: Blood samples were
      obtained from all patients for serum cortisol measurements and DNA isolation.
      Demographic and illness severity data were collected. MEASUREMENTS AND MAIN
      RESULTS: Single nucleotide polymorphisms were tested for association with serum
      free cortisol concentrations in context of higher illness severity as quantified
      by Pediatric Risk of Mortality III score greater than 7. A single nucleotide
      polymorphism (rs1941088) in the MC2R gene was strongly associated (p = 0.0005)
      with a low free cortisol response to critical illness. Patients with the AA
      genotype were over seven times more likely to have a low free cortisol response
      to critical illness than those with a GG genotype. Patients with the GA genotype
      exhibited an intermediate free cortisol response to critical illness.
      CONCLUSIONS: The A allele at rs1941088 in the MC2R gene, which encodes the
      adrenocorticotropic hormone (corticotropin, ACTH) receptor, is associated with a
      low cortisol response in critically ill children. These data provide evidence for
      a genetic basis for a portion of the variability in cortisol production during
      critical illness. Independent replication of these findings will be important and
      could facilitate development of personalized treatment for patients with a low
      cortisol response to severe illness.

PMID- 25055196
TI  - Intracellular delivery of antisense peptide nucleic acid by fluorescent
      mesoporous silica nanoparticles.
AB  - In order to overcome poor cell permeability of antisense peptide nucleic acid
      (PNA), a fluorescent mesoporous silica nanoparticle (MSNP) carrier was developed
      to successfully deliver antisense PNA into cancer cells for effective silence of
      B-cell lymphoma 2 (Bcl-2) protein expression in vitro. First, fluorescent MSNP
      functionalized with disulfide bond bridged groups was fabricated and
      characterized. Antisense and negative control PNAs were synthesized and further
      conjugated with fluorescent dye cyanine 5. Then, the PNAs were covalently
      connected with fluorescent MSNP via amidation between amino group of PNAs and
      carboxylic acid group on the MSNP surface. High intracellular concentration of
      glutathione serves as a natural reducing agent, which could cleave the disulfide
      bond to trigger the PNA release in vitro. Confocal laser scanning microscopy
      studies prove that PNA conjugated MSNP was endocytosed by HeLa cancer cells, and
      redox-controlled intracellular release of antisense PNA from fluorescent MSNP was
      successfully achieved. Finally, effective silencing of the Bcl-2 protein
      expression induced by the delivered antisense PNA into HeLa cells was confirmed
      by Western blot assay. 

PMID- 25055197
TI  - Implementation of the patient-centered medical home in the Veterans Health
      Administration: associations with patient satisfaction, quality of care, staff
      burnout, and hospital and emergency department use.
AB  - IMPORTANCE: In 2010, the Veterans Health Administration (VHA) began implementing
      the patient-centered medical home (PCMH) model. The Patient Aligned Care Team
      (PACT) initiative aims to improve health outcomes through team-based care,
      improved access, and care management. To track progress and evaluate outcomes at
      all VHA primary care clinics, we developed and validated a method to assess PCMH
      implementation. OBJECTIVES: To create an index that measures the extent of PCMH
      implementation, describe variation in implementation, and examine the association
      between the implementation index and key outcomes. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted an observational study using data on more than 5.6
      million veterans who received care at 913 VHA hospital-based and community-based
      primary care clinics and 5404 primary care staff from (1) VHA clinical and
      administrative databases, (2) a national patient survey administered to a
      weighted random sample of veterans who received outpatient care from June 1 to
      December 31, 2012, and (3) a survey of all VHA primary care staff in June 2012.
      Composite scores were constructed for 8 core domains of PACT: access, continuity,
      care coordination, comprehensiveness, self-management support, patient-centered
      care and communication, shared decision making, and team-based care. MAIN
      OUTCOMES AND MEASURES: Patient satisfaction, rates of hospitalization and
      emergency department use, quality of care, and staff burnout. RESULTS: Fifty
      three items were included in the PACT Implementation Progress Index (Pi2).
      Compared with the 87 clinics in the lowest decile of the Pi2, the 77 sites in the
      top decile exhibited significantly higher patient satisfaction (9.33 vs 7.53; P <
      .001), higher performance on 41 of 48 measures of clinical quality, lower staff
      burnout (Maslach Burnout Inventory emotional exhaustion subscale, 2.29 vs 2.80; P
      = .02), lower hospitalization rates for ambulatory care-sensitive conditions
      (4.42 vs 3.68 quarterly admissions for veterans 65 years or older per 1000
      patients; P < .001), and lower emergency department use (188 vs 245 visits per
      1000 patients; P < .001). CONCLUSIONS AND RELEVANCE: The extent of PCMH
      implementation, as measured by the Pi2, was highly associated with important
      outcomes for both patients and providers. This measure will be used to track the
      effectiveness of implementing PACT over time and to elucidate the correlates of
      desired health outcomes.

PMID- 25055198
TI  - Inflammatory hepatocellular adenomas can mimic focal nodular hyperplasia on
      gadoxetic acid-enhanced MRI.
AB  - OBJECTIVE: Inflammatory hepatocellular adenoma (HCA) is a recently categorized
      entity of hepatocellular neoplasms. We investigated whether gadoxetic acid
      enhanced MRI can distinguish inflammatory HCA from focal nodular hyperplasia
      (FNH). MATERIALS AND METHODS: From January 1, 2009, through January 1, 2013,
      gadoxetic acid-enhanced MRI examinations from two institutions were reviewed for
      HCA, with specific histologic features of inflammatory HCA. Biopsy and resection
      slides were reviewed, and immunohistochemistry for glutamine synthetase was
      performed in a subset to confirm the initial diagnosis. RESULTS: A total of 10
      possible cases of inflammatory HCA were identified in the pathology database. On
      the basis of glutamine synthetase staining performed for this study, three cases
      were rediagnosed as FNH and thus were excluded from the study. Therefore, a total
      of seven patients with inflammatory HCA were identified. On gadoxetic acid
      enhanced MRI, four of these patients had classic features of FNH (group A, FNH
      mimics), and three had imaging features suggestive of HCA (group B, typical
      inflammatory HCA). Imaging features that were considered diagnostic of FNH
      included isointense or minimal T2 hyperintensity, arterial enhancement, and
      diffuse hyperintensity on hepatobiliary phase. Three of the four patients with
      FNH mimics had slides available for pathologic rereview, and the diagnosis of
      inflammatory HCA was supported by glutamine synthetase immunohistochemistry
      findings. The pathology reports of the remaining four cases were rereviewed and
      were also found to have features consistent with inflammatory HCA. CONCLUSION:
      Inflammatory HCA can mimic FNH on MRI, including hepatobiliary phase
      hyperintensity. Moreover, conventional pathology using histopathology alone may
      lead to misclassification of inflammatory HCA.

PMID- 25055200
TI  - An efficient estimator of the mutation parameter and analysis of polymorphism
      from the 1000 genomes project.
AB  - The mutation parameter theta is fundamental and ubiquitous in the analysis of
      population samples of DNA sequences. This paper presents a new highly efficient
      estimator of theta by utilizing the phylogenetic information among distinct
      alleles in a sample of DNA sequences. The new estimator, called Allelic BLUE, is
      derived from a generalized linear model about the mutations in the allelic
      genealogy. This estimator is not only highly accurate, but also computational
      efficient, which makes it particularly useful for estimating theta for large
      samples, as well as for a large number of cases, such as the situation of
      analyzing sequence data from a large genome project, such as the 1000 Genomes
      Project. Simulation shows that Allelic BLUE is nearly unbiased, with variance
      nearly as small as the minimum achievable variance, and in many situations, it
      can be hundreds- or thousands-fold more efficient than a previous method, which
      was already quite efficient compared to other approaches. One useful feature of
      the new estimator is its applicability to collections of distinct alleles without
      detailed frequencies. The utility of the new estimator is demonstrated by
      analyzing the pattern of theta in the data from the 1000 Genomes Project. 

PMID- 25055199
TI  - From genotype to functional phenotype: unraveling the metabolomic features of
      colorectal cancer.
AB  - Much effort in recent years has been expended in defining the genomic and
      epigenetic alterations that characterize colorectal adenocarcinoma and its
      subtypes. However, little is known about the functional ramifications related to
      various subtypes. Metabolomics, the study of small molecule intermediates in
      disease, provides a snapshot of the functional phenotype of colorectal cancer.
      Data, thus far, have characterized some of the metabolic perturbations that
      accompany colorectal cancer. However, further studies will be required to
      identify biologically meaningful metabolic subsets, including those corresponding
      to specific genetic aberrations. Moreover, further studies are necessary to
      distinguish changes due to tumor and the host response to tumor. 

PMID- 25055201
TI  - The challenges of genome analysis in the health care setting.
AB  - Genome sequencing is now a sufficiently mature and affordable technology for
      clinical use. Its application promises not only to transform clinicians'
      diagnostic and predictive ability, but also to improve preventative therapies,
      surveillance regimes, and tailor patient treatment to an individual's genetic
      make-up. However, as with any technological advance, there are associated fresh
      challenges. While some of the ethical, legal and social aspects resulting from
      the generation of data from genome sequencing are generic, several nuances are
      unique. Since the UK government recently announced plans to sequence the genomes
      of 100,000 Health Service patients, and similar initiatives are being considered
      elsewhere, a discussion of these nuances is timely and needs to go hand in hand
      with formulation of guidelines and public engagement activities around
      implementation of sequencing in clinical practice. 

PMID- 25055203
TI  - Functional gene-set analysis does not support a major role for synaptic function
      in attention deficit/hyperactivity disorder (ADHD).
AB  - Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common
      childhood-onset neuropsychiatric disorders. Despite high heritability estimates,
      genome-wide association studies (GWAS) have failed to find significant genetic
      associations, likely due to the polygenic character of ADHD. Nevertheless,
      genetic studies suggested the involvement of several processes important for
      synaptic function. Therefore, we applied a functional gene-set analysis to
      formally test whether synaptic functions are associated with ADHD. Gene-set
      analysis tests the joint effect of multiple genetic variants in groups of
      functionally related genes. This method provides increased statistical power
      compared to conventional GWAS. We used data from the Psychiatric Genomics
      Consortium including 896 ADHD cases and 2455 controls, and 2064 parent-affected
      offspring trios, providing sufficient statistical power to detect gene sets
      representing a genotype relative risk of at least 1.17. Although all synaptic
      genes together showed a significant association with ADHD, this association was
      not stronger than that of randomly generated gene sets matched for same number of
      genes. Further analyses showed no association of specific synaptic function
      categories with ADHD after correction for multiple testing. Given current sample
      size and gene sets based on current knowledge of genes related to synaptic
      function, our results do not support a major role for common genetic variants in
      synaptic genes in the etiology of ADHD. 

PMID- 25055202
TI  - Genes and genetic testing in hereditary ataxias.
AB  - Ataxia is a neurological cerebellar disorder characterized by loss of
      coordination during muscle movements affecting walking, vision, and speech.
      Genetic ataxias are very heterogeneous, with causative variants reported in over
      50 genes, which can be inherited in classical dominant, recessive, X-linked, or
      mitochondrial fashion. A common mechanism of dominant ataxias is repeat
      expansions, where increasing lengths of repeated DNA sequences result in non
      functional proteins that accumulate in the body causing disease. Greater
      understanding of all ataxia genes has helped identify several different pathways,
      such as DNA repair, ubiquitination, and ion transport, which can be used to help
      further identify new genes and potential treatments. Testing for the most common
      mutations in these genes is now clinically routine to help with prognosis and
      treatment decisions, but next generation sequencing will revolutionize how
      genetic testing will be done. Despite the large number of known ataxia causing
      genes, however, many individuals with ataxia are unable to obtain a genetic
      diagnosis, suggesting that more genes need to be discovered. Utilization of next
      generation sequencing technologies, expression studies, and increased knowledge
      of ataxia pathways will aid in the identification of new ataxia genes. 

PMID- 25055204
TI  - Microbial source tracking in a coastal California watershed reveals canines as
      controllable sources of fecal contamination.
AB  - Elevated levels of fecal indicator bacteria (FIB), including Escherichia coli and
      enterococci, trigger coastal beach advisories and signal public health risks.
      Solving FIB pollution in suburban coastal watersheds is challenging, as there are
      many potential sources. The Arroyo Burro watershed in Santa Barbara, CA is an
      example, with its popular, but chronically FIB-contaminated beach. To address, a
      microbial source tracking study was performed. Surface waters were sampled over 2
      years, FIB were quantified, and DNA was analyzed for host-associated fecal
      markers. Surf zone FIB were only elevated when the coastal lagoon was
      discharging. Among the fecal sources into the lagoon, including upstream human
      sources and coastal birds, canines were the most important. Canine sources
      included input via upstream creek water, which decreased after creek-side
      residences were educated about proper pet waste disposal, and direct inputs to
      the lagoon and surf zone, where dog waste could have been tidally exchanged with
      the lagoon. Based on this study, canine waste can be an influential, yet
      controllable, fecal source to suburban coastal beaches. 

PMID- 25055205
TI  - Rotenone isolated from Pachyrhizus erosus displays cytotoxicity and genotoxicity
      in K562 cells.
AB  - Pachyrhizus erosus (Fabaceae) is a herb commonly known as 'yam bean', which has
      been cultivated in Mexico since pre-Columbian times for its edible tubers. The
      seeds are also known for their acaricidal and insecticidal properties due to
      rotenone and other isoflavonoid contents. Rotenone has exhibited cytotoxic
      activity against several human tumour cell lines; however, its mechanism of
      action is still not fully understood. In this study, we determined the
      cytotoxicity of rotenone isolated from P. erosus seeds on K562 human leukaemia
      cells. Rotenone exhibited significant cytotoxic activity (IC50 = 13.05 MUM), as
      determined by the MTT assay. Three other isolated isoflavonoids were not
      cytotoxic. Rotenone genotoxicity was detected using the comet assay. Rotenone
      induced cell death, and caspase-3 activation as indicated by TUNEL assay, and
      immunocytofluorescence. Plasmid nicking assay indicated that rotenone does not
      interact directly with DNA.

PMID- 25055206
TI  - Treatment of hiccup by vagal maneuvers.
AB  - A multitude of nonpharmacological interventions to terminate hiccup belong to the
      public-domain hiccup "mythology" or have been described in the medical literature
      as case reports. While usually effective in terminating bouts of acute hiccup,
      they are mostly ineffective in cases of hiccupping that have been present for an
      extended period. The common denominator of most of these therapeutic maneuvers
      (some also used to terminate paroxysmal supraventricular tachycardia) is their
      ability to directly or indirectly increase efferent vagal activity. Among the
      best known "vagal maneuvers" are the oculo-cardiac reflex (Dagnini-Aschner), the
      carotid sinus massage, the Valsalva maneuver, stimulation of the ear/auditory
      canal, ice ingestion, and induction of emesis. This short report provides an
      overview on hiccups and attempts to identify the lesser known personalities who
      pioneered its treatment by vagal maneuvers. The recent introduction of electrical
      vagus nerve stimulation for therapy-resistant hiccup is the ultimate compliment
      to these pioneers.

PMID- 25055207
TI  - Characterization of protein serotonylation via bioorthogonal labeling and
      enrichment.
AB  - Protein serotonylation is a transglutaminase-mediated phenomenon whose biological
      mechanism of protein serotonylation is not yet fully understood, as the complete
      profiling of serotonylation targets in a proteome remains a critical challenge to
      date. Utilizing an alkyne-functionalized serotonin derivative bioorthogonally
      coupled to a cleavable linker, we developed a method to selectively enrich
      serotonylated proteins in a complex sample. With online nanoflow liquid
      chromatography and LTQ-Orbitrap Velos hybrid mass spectrometer detection, we
      identified 46 proteins with 50 serotonylation sites at their glutamine residues.
      Mass spectrometric analysis also generated direct residue-level evidence of
      various biological processes such as transglutaminase-chaperon interactions as
      well as actin assembly. An enrichment workflow utilizing click chemistry and on
      bead digestion allowed us to achieve site-specific identification of protein
      serotonylation by mass spectrometry, and results obtained hereby also provided a
      great foundation in the elucidation of the true roles of protein serotonylation
      in biological systems. 

PMID- 25055209
TI  - Neural Network Analysis of Different Segmentation Strategies of Nerve Fiber Layer
      Assessment for Glaucoma Diagnosis.
AB  - PURPOSE: To compare the diagnostic performance of different segmentations of the
      nerve fiber layer (NFL) thickness measurements using an artificial neural network
      and to define the optimal number of sectors with best diagnostic ability for
      glaucoma diagnosis. METHODS: A total of 117 glaucoma patients and 123 normal
      subjects were included in the study. NFL thickness measurements were performed
      using the Spectralis-OCT (Heidelberg Engineering) to obtain the NFL thickness
      average; measurements from 2 semicircles, 4 quadrants, and 6, 8, 12, 16, 24, 32,
      and 64 sectors; and 768 uniformly divided locations around the peripapillary NFL.
      An artificial neural network evaluation was performed to compare the influence of
      sector analysis on the diagnostic performance of optical coherence tomography.
      Receiver operating characteristic curves were used to compare the diagnostic
      ability of the different segmentation analyses. RESULTS: The 6 sectors divided by
      the horizontal division of the nasal and temporal quadrants were better than the
      6 sectors divided by the vertical line through the superior and inferior
      quadrants [areas under curve, 0.778; 95% confidence interval (CI), 0.720-0.829
      and 0.814; 95% CI, 0.759-0.861, respectively]. In the case of quadrants, clock
      quadrants (area under curve 0.770; 95% CI, 0.712-0.822) were better than the ISNT
      (inferior-superior-nasal-temporal) quadrants (area under curve, 0.770; 95% CI,
      0.712-0.822; P=0.003). The first segmentation strategy that improved the
      diagnostic value of 4 ISNT quadrants was the 12-sector analysis (area under
      curve, 0.845; 95% CI, 0.793-0.889; P=0.001). CONCLUSIONS: The 2 best candidate
      strategies for the OCT report were the 12-sector analysis and the 4 planimetric
      quadrant (alternatively, the 4 clock quadrants) analysis.

PMID- 25055208
TI  - The impact of central corneal thickness on the risk for glaucoma in a large
      multiethnic population.
AB  - PURPOSE: To investigate the relationship between central corneal thickness (CCT)
      and demographics, and determine whether CCT may be a substantial mediator of the
      relationships between glaucoma and its demographic risk factors. METHODS: This
      cross-sectional study included patients in the Kaiser Permanente Northern
      California health plan from January 1, 2007 to December 31, 2011 who were 40
      years and older and had a documented CCT measurement (N=81,082). Those with any
      cornea-related diagnoses or a history of corneal refractive surgery were
      excluded. Demographic characteristics, including age, sex, and race/ethnicity, as
      well as clinical information including glaucoma-related diagnosis, diabetic
      status, CCT, and intraocular pressure were gathered from the electronic medical
      record. RESULTS: Multivariate linear regression analysis indicated that female
      sex, increased age, and black race were significantly associated with thinner
      corneas. A subgroup analysis among Asians revealed that Chinese, Japanese, and
      Koreans had corneas 6 to 13 um thicker than South and Southeast Asians,
      Filipinos, and Pacific Islanders for each diagnosis (P<0.001). In our population,
      24.5% (N=19878) had some form of open-angle glaucoma; 21.9% (N=17,779) did not
      have any glaucoma-related diagnosis. Variation in CCT accounted for only 6.68%
      [95% confidence interval (CI), 6.14%-7.24%] of the increased risk of open-angle
      glaucoma seen with increasing age, but explained as much as 29.4% (95% CI, 27.0%
      32.6%) of the increased risk of glaucoma seen among blacks, and 29.5% (95% CI,
      23.5%-37.0%) of the increased risk of glaucoma seen among Hispanics. CONCLUSIONS:
      CCT seems to explain a substantial portion of the increased risk of glaucoma seen
      among blacks and Hispanics.

PMID- 25055210
TI  - The relationship between sociodemographic factors and persistence with topical
      glaucoma medications.
AB  - PURPOSE: To investigate the relationship between sociodemographic factors and
      nonpersistence with topical glaucoma medication. DESIGN: This was a
      retrospective, observational cohort study. PATIENTS AND METHODS: We invited
      glaucoma patients on medical therapy from a general ophthalmology practice to
      complete a standardized questionnaire between November 2011 and April 2012.
      Nonpersistence was defined as having >= 1 gaps (>= 14 d without medication) in
      therapy over the last year. Patients' pharmacy records, dating back 1 year from
      study enrollment, were used to determine the total number of gaps and the
      cumulative number of days off therapy in the last year. Prevalence ratios (PR)
      and 95% confidence intervals (CI) were used to assess the relationship between
      sociodemographic factors and nonpersistence. The relationships between
      sociodemographic factors and the median number of gaps, as well as the median
      number of days off, were also assessed. RESULTS: Sixty-one patients were included
      for analysis. The mean age was 72 years; 61% were male patients and 71% were on
      one medication for glaucoma. Fifty-four percent of patients (n=33) were
      nonpersistent with glaucoma medications over the 1 year study period. Median
      numbers of gaps and days off therapy were 1 and 11, respectively. Patients
      reporting below average income were twice as likely to be nonpersistent
      (prevalence ratio, 2.02; 95% confidence interval, 1.37-2.96; P<0.01). Below
      average income also trended toward a greater median number of days off therapy
      (P=0.07). CONCLUSIONS: Below average socioeconomic status may negatively impact
      persistence with topical glaucoma medications, potentially threatening long-term
      visual outcomes.

PMID- 25055211
TI  - Postiridotomy ultrasound biomicroscopy features in the fellow eye of Chinese
      patients with acute primary angle-closure and chronic primary angle-closure
      glaucoma.
AB  - PURPOSE: To compare the features of postiridotomy ultrasound biomicroscopy (UBM)
      in Chinese patients with acute primary angle-closure (aPAC) and with chronic
      primary angle-closure (cPAC) glaucoma. PATIENTS AND METHODS: Consecutive cases
      were classified into acute and chronic groups. The acute group included 77
      patients with unilateral aPAC. The chronic group included 57 patients with
      unilateral advanced cPAC glaucoma. In both the groups, the patients' fellow eye
      underwent a laser iridotomy and was studied. The main outcome measures included
      qualitative UBM parameters such as a plateau iris, anterior iris insertion, and
      an anteriorly rotated ciliary process and quantitative UBM parameters such as
      central anterior chamber depth (ACD), basal iris thickness (IT500), and scleral
      ciliary process angle (SCPA). RESULTS: For the qualitative parameters, more eyes
      in the chronic group had a plateau iris (P=0.046), an anterior iris insertion
      (P=0.222), and an anteriorly rotated ciliary process (P=0.090) than those in the
      acute group. For the quantitative parameters, the eyes in the chronic group had a
      deeper ACD (P<0.001), thicker IT500 (P<0.001), and smaller SCPA (P<0.001) than
      those in the acute group. CONCLUSIONS: The UBM features of Chinese patients with
      cPAC include a more plateaued iris, a thicker basal iris, and a smaller SCPA,
      whereas patients with aPAC may have a shallower ACD. For Chinese patients, a
      nonpupillary block component may play a more important role in asymptomatic cPAC
      than in aPAC.

PMID- 25055212
TI  - Prevalence of angle closure in siblings of patients with primary angle-closure
      glaucoma.
AB  - PURPOSE: To determine the frequency of angle closure in siblings of patients with
      primary angle-closure glaucoma (PACG). METHODS: In this cross-sectional
      observational study, siblings of consecutive patients with PACG underwent a
      comprehensive ophthalmologic examination, including slit-lamp biomicroscopy,
      measurement of intraocular pressure, stereoscopic optic nerve head examination,
      and dynamic gonioscopy. Ultrasonic pachymetry was obtained in all subjects;
      peripapillary retinal nerve fiber layer thickness measurement by optical
      coherence tomography and standard achromatic perimetry were performed in subjects
      with angle closure, categorized as primary angle-closure suspect (PACS), primary
      angle closure (PAC), and PACG, or any suspicion of glaucoma in the presence of
      open angles. RESULTS: Overall, 95 siblings from 47 families with at least 1
      subject affected with PACG participated in the evaluations; 55 (57.9%)
      individuals were categorized within the spectrum of angle closure, including 34
      (35.8%) subjects with PACS, 7 (7.4%)individuals with PAC, and 14 (14.7%) cases of
      PACG. Nine (9.5%) individuals with open angles demonstrated other abnormal
      features, these included 3 (3.2%) subjects with suspicious discs, 5 (5.3%) cases
      of primary open-angle glaucoma, and 1 patient (1.1%) with normal-tension
      glaucoma. The remaining 31 individuals (32.6%) had no evidence of glaucoma.
      CONCLUSIONS: Our findings indicate familial segregation of angle closure.
      Siblings of PACG patients are at high risk for the condition, such that two
      thirds of them demonstrate clinical findings related to glaucoma. These
      observations suggest a hereditary basis for angle closure; therefore, siblings of
      patients affected with angle closure should undergo targeted screening for
      glaucoma.

PMID- 25055214
TI  - Influence of a new software version of the RTVue-100 optical coherence tomograph
      on ganglion cell complex segmentation in various forms of age-related macular
      degeneration.
AB  - PURPOSE: Previously, we have shown that age-related macular degeneration (AMD)
      influences glaucoma classification with the ganglion cell complex (GCC)
      parameters of the RTVue-100 optical coherence tomograph (RTVue-OCT) in
      nonglaucomatous eyes. Now, we reevaluated the influence of AMD on GCC image
      segmentation and classification for glaucoma on the same eyes, using a new
      version of the software. METHODS: GCC images of nonglaucomatous eyes [30 healthy,
      19 with early/intermediate AMD, 16 with subfoveal choroidal neovascularization
      (CNV), and 19 after intravitreal antiangiogenic treatment of CNV, CNV-anti-VEGF]
      were reanalyzed with software versions 6.3 (the currently available version) and
      6.12 (a version not yet commercially released). RESULTS: Global loss volume (GLV)
      was significantly reduced with version 6.12 in all groups (P<=0.0416).
      Segmentation errors were seen in 2 versus 0 of the normal eyes (P=0.500), 8
      versus 0 of the early/intermediate AMD eyes (P=0.0312), 16 versus 6 of the CNV
      eyes (P=0.0080), and 18 versus 3 of the CNV-anti-VEGF eyes (P=0.0004) with
      software versions 6.3 and 6.12, respectively. For focal loss volume the
      distribution of the classification results differed significantly between the
      software versions in the CNV and CNV-anti-VEGF groups (P=0.0312 and 0.0160,
      respectively). For both groups more eyes were classified as "within normal
      limits," and less as "outside normal limits" with software version 6.12 than with
      version 6.3. CONCLUSIONS: For nonglaucomatous AMD eyes the frequency of GCC
      segmentation errors was significantly reduced, GLV was significantly lower (more
      normal), and the classification for glaucoma was more correct with software
      version 6.12 than with version 6.3.

PMID- 25055213
TI  - Reduction of conjunctival fibrosis after trabeculectomy using topical alpha
      lipoic acid in rabbit eyes.
AB  - PURPOSE: To evaluate the efficacy of alpha-lipoic acid (ALA) in reducing scarring
      after trabeculectomy. MATERIALS AND METHODS: Eighteen adult New Zealand white
      rabbits underwent trabeculectomy. During trabeculectomy, thin sponges were placed
      between the sclera and Tenon's capsule for 3 minutes, saline solution, mitomycin
      C (MMC) and ALA was applied to the control group (CG) (n=6 eyes), MMC group
      (MMCG) (n=6 eyes), and ALA group (ALAG) (n=6 eyes), respectively. After surgery,
      topical saline and ALA was applied for 28 days to the control and ALAGs,
      respectively. Filtrating bleb patency was evaluated by using 0.1% trepan blue.
      Hematoxylin and eosin and Masson trichrome staining for toxicity, total
      cellularity, and collagen organization; alpha-smooth muscle actin
      immunohistochemistry staining performed for myofibroblast phenotype
      identification. RESULTS: Clinical evaluation showed that all 6 blebs (100%) of
      the CG had failed, whereas there were only 2 failures (33%) in the ALAG and no
      failures in the MMCG on day 28. Histologic evaluation showed significantly lower
      inflammatory cell infiltration in the ALAGs and CGs than the MMCG. Toxicity
      change was more significant in the MMCG than the control and ALAGs. Collagen was
      better organized in the ALAG than control and MMCGs. In immunohistochemistry
      evaluation, ALA significantly reduced the population of cells expressing alpha
      smooth muscle action. CONCLUSIONS: AlphaLA prevents and/or reduces fibrosis by
      inhibition of inflammation pathways, revascularization, and accumulation of
      extracellular matrix. It can be used as an agent for delaying tissue regeneration
      and for providing a more functional-permanent fistula.

PMID- 25055215
TI  - Intraocular pressure curves of untreated glaucoma suspects and glaucoma patients
      in sitting and lateral decubitus positions using the goldmann applanation
      tonometer.
AB  - PURPOSE: Evaluation of data obtained during diurnal intraocular pressure (IOP)
      measurements by means of the Goldmann Applanation tonometer in sitting and
      lateral decubitus positions. PATIENTS AND METHODS: Retrospective cohort study of
      41 consecutive untreated subjects (82 eyes) with ocular hypertension or
      suspicious discs. The IOP was measured by Goldmann Applanation tonometer in
      sitting position at 9 AM, 12 AM, 3 PM, and 6 PM; and in right lateral decubitus
      position around 12:15 PM. RESULTS: In the right eye (RE) mean peak IOP was
      22.19+/-4.68 mm Hg. In the left eye (LE) peak mean IOP was 22.19+/-3.8 mm Hg. In
      91.5% of the eyes, the IOP increased in the lateral decubitus position. The
      average change in the RE was an increment of 4.22+/-2.67 mm Hg (P<0.001) and in
      the LE an increment of 3.51+/-3.11 (P<0.001). This increment was significantly
      higher in the dependent eye (i.e., lower eye) (P=0.049). Sixty-seven percent of
      eyes had a positional elevation of IOP between 2 and 5 mm Hg and 23.2% of eyes
      had IOP elevation between 6 and 12 mm Hg. In the great majority of the eyes
      (80.5% RE and 78% LE) the lateral decubitus IOP was greater than maximal diurnal
      sitting IOP. CONCLUSIONS: The IOP in the lateral decubitus position was
      significantly higher than the mean maximal diurnal sitting IOP. Over 20% of the
      patients had an IOP increase of >=6 mm Hg when lying down. Timely identification
      of patients with excessive postural elevation of IOP could affect their
      management and prevent visual fields loss.

PMID- 25055216
TI  - Long range ordered magnetic and atomic structures of the quasicrystal approximant
      in the Tb-Au-Si system.
AB  - The atomic and magnetic structure of the 1/1 Tb(14)Au(70)Si(16) quasicrystal
      approximant has been solved by combining x-ray and neutron diffraction data. The
      atomic structure is classified as a Tsai-type 1/1 approximant with certain
      structural deviations from the prototype structures; there are additional atomic
      positions in the so-called cubic interstices as well as in the cluster centers.
      The magnetic property and neutron diffraction measurements indicate the magnetic
      structure to be ferrimagnetic-like below 9 K in contrast to the related
      Gd(14)Au(70)Si(16) structure that is reported to be purely ferromagnetic.

PMID- 25055217
TI  - Study of the nanoscale morphology of polythiophene fibrils and a fullerene
      derivative.
AB  - Nanoscale blending of electron-donor and electron-acceptor materials in solution
      processed bulk heterojunction organic photovoltaic devices is crucial for
      achieving high power conversion efficiency. We used a classic blend of poly(3
      hexylthiophene)/phenyl-C61-butyric acid methyl ester (P3HT/PCBM) as a model to
      observe the nanoscale morphology of the P3HT fibrils and PCBM nanoclusters in the
      mixture. Energy-filtered transmission electron microscopy (EFTEM) clearly
      revealed a nanoscopic phase separation. Randomly connected and/or nonconnected
      P3HT fibrous networks and PCBM domains, revealed by 2-dimensional micrographs,
      were observed by collecting electron energy loss spectra in the range of 19-30
      eV. From EFTEM images, the average length and the diameter of P3HT fibrils were
      found to be approximately 70 +/- 5 and 15 +/- 2 nm, respectively. Combining the
      EFTEM, selected area electron diffraction, and X-ray diffraction results, the
      number and spacing of the ordered chains in P3HT fibrils were determined. There
      were 18 +/- 3 repeating units of P3HT perpendicular to the fibril, ~184 layers of
      pi-pi stacking along the fibril, and ~9 layers of interchain stacking within the
      fibril. These conclusive observations provide insight into the number of
      molecules found in one instance of ordered-plane stacking. This information is
      useful for the calculation of charge transport in semicrystalline polymers. Using
      cross-section samples prepared with a focused ion beam technique, the vertical
      morphology of each phase was analyzed. By collecting 30 eV energy loss images,
      the phase separation in the P3HT/PCBM system was distinguishable. A higher P3HT
      concentration was observed at the top of the cell, near Al contact, which could
      possibly cause loss of carriers and recombination due to a mismatch in the P3HT
      and Al energy bands. 

PMID- 25055220
TI  - Mouthwashes for the control of supragingival biofilm and gingivitis in
      orthodontic patients: evidence-based recommendations for clinicians.
AB  - Properly performed daily mechanical biofilm control is the most important
      prevention strategy for periodontal diseases. However, proper mechanical biofilm
      control is not performed effectively by the majority of the population, mainly
      due to lack of motivation and of manual dexterity. Local biofilm retention
      factors may aggravate home oral hygiene quality. For this reason, patients
      wearing fixed orthodontic appliances comprise a group that may benefit from the
      daily use of mouthwashes. The purpose of this review was to perform a systematic
      search in the literature on antiseptics used to control supragingival biofilm and
      gingivitis in orthodontic patients. Six studies investigating the effect of
      chlorhexidine and 5 studies evaluating the effect of the daily use of antiseptics
      were found. Chlorhexidine showed better results in reducing plaque and
      gingivitis. However, because of its adverse effects after continuous use, it
      should not be indicated for long-term periods. Among the agents considered for
      daily use, the fixed combination of essential oils was the only one evaluated in
      a clinical trial, in which a comparative group presented a statistically
      significant clinical impact. There is no direct evidence supporting the
      indication of antiseptic agents for orthodontic patients other than chlorhexidine
      and essential oils. It can be concluded that, for patients undergoing orthodontic
      treatment, chlorhexidine should be considered for treating acute gingival
      inflammation, whereas essential oils should be indicated for long-term daily use
      in controlling supragingival biofilm.

PMID- 25055224
TI  - Isostructural synthesis of porous metal-organic nanotubes.
AB  - Employment of semirigid double-hinged di-1,2,4-triazoles has led to the synthesis
      of an isostructural series of metal-organic nanotubes (MONTs). The ditriazole
      ligands adopt a syn conformation between rigid metal chains while an appropriate
      anion choice provides a "capping" of the metal ions, leading to MONT formation.
      This approach of utilizing a variety of both semirigid ligands and metals is the
      first general methodology to prepare this class of 1D nanomaterial. The local
      geometry at the metal center depends on the metal ion employed, with Cu(I)
      centers adopting a tetrahedral geometry, Ag(I) centers adopting a seesaw
      geometry, and Cu(II) centers adopting a square-pyramidal geometry upon MONT
      synthesis. The pore size of the MONTs is adjusted by changing the central portion
      of the double-hinged ligand, allowing for a predictable method to control the
      pore width of the MONT. The adsorption properties of MONTs as a function of pore
      size revealed selective uptake of CO2 and CH4, with copper MONTs exhibiting the
      highest uptake. In the case of the silver MONTs, an increase in pore width
      improves both gas uptake and selectivity. 

PMID- 25055225
TI  - Thermal transitions in hydrated layer-by-layer assemblies observed using
      electrochemical impedance spectroscopy.
AB  - Layer-by-layer (LbL) assemblies have been of great interest due to their
      versatile functionality and ease of fabrication, but their response to
      temperature is not completely understood. It has been recently shown that
      hydrated LbL assemblies of poly(diallyldimethylammonium chloride) (PDAC) and
      poly(styrene sulfonate) (PSS) under go a thermal transition much like a "glass
      melt" transition. This thermal transition is of great interest because many LbL
      applications are found in water. Here, we report upon the nature of this thermal
      transition as probed using electrochemical impedance spectroscopy (EIS) as a
      function of assembly salt concentration, film thickness, and outermost layer. EIS
      reveals that the transition is signified by a structural rearrangement of virtual
      pores, resulting in increased conductivity and decreased surface coverage of the
      electrode. Two separate thermal transitions are obtained from changes in the film
      resistance (Ttr,Rf) and the charge transfer resistance (Ttr,Rct). Only Ttr,Rct is
      strongly dependent on film thickness, salt concentration, and outermost layer,
      for which values ranging from 50 to 64  degrees C were observed. As the assembly
      salt concentration increases from 0.5 M to 1.0 M NaCl, Ttr,Rct increases by about
      10  degrees C. Below 20 layers, deviations of Ttr,Rct with respect to outermost
      layer appear, in which PSS-capped LbL films tend to show elevated Ttr,Rct values.
      These results suggest that extrinsic charge compensation plays a large role in
      the value of Ttr,Rct in which a large degree of extrinsic charge compensation
      drives Ttr,Rct towards higher values. On the other hand, Ttr,Rf is largely
      unaffected by assembly parameters, and closer in value to prior reports via
      calorimetry and quartz crystal microbalance with dissipation. 

PMID- 25055226
TI  - Spacer geometry and particle deposition in spiral wound membrane feed channels.
AB  - Deposition of microspheres mimicking bacterial cells was studied experimentally
      and with a numerical model in feed spacer membrane channels, as used in spiral
      wound nanofiltration (NF) and reverse osmosis (RO) membrane systems. In-situ
      microscopic observations in membrane fouling simulators revealed formation of
      specific particle deposition patterns for different diamond and ladder feed
      spacer orientations. A three-dimensional numerical model combining fluid flow
      with a Lagrangian approach for particle trajectory calculations could describe
      very well the in-situ observations on particle deposition in flow cells. Feed
      spacer geometry, positioning and cross-flow velocity sensitively influenced the
      particle transport and deposition patterns. The deposition patterns were not
      influenced by permeate production. This combined experimental-modeling approach
      could be used for feed spacer geometry optimization studies for reduced
      (bio)fouling. 

PMID- 25055227
TI  - Orthogonal control of antibacterial activity with light.
AB  - Selection of a single bacterial strain out of a mixture of microorganisms is of
      crucial importance in healthcare and microbiology research. Novel approaches that
      can externally control bacterial selection are a valuable addition to the
      microbiology toolbox. In this proof-of-concept, two complementary antibiotics are
      protected with photocleavable groups that can be orthogonally addressed with
      different wavelengths of light. This allows for the light-triggered selection of
      a single bacterial strain out of a mixture of multiple strains, by choosing the
      right wavelength. Further improvement toward additional orthogonally addressable
      antibiotics might ultimately lead to a novel methodology for bacterial selection
      in complex populations. 

PMID- 25055228
TI  - Reconstruction of the temporomandibular joint after surgical ablation of a
      multiply recurrent ameloblastoma: a case report.
AB  - Reconstruction of large mandibular defects, whether involving the
      temporomandibular joint (TMJ) or not, has historically been achieved with
      autogenous grafts, such as free costochondral grafts and vascularized bone
      grafts. Ensuring intact, functioning microcirculation is critical for graft
      survival in the face of postoperative radiation therapy secondary to malignant
      tumour ablation. However, in the case of benign tumours, such as ameloblastomas,
      postoperative radiation therapy is not required, thus increasing the options for
      reconstruction. Alloplastic components coupled with nonvascularized bone grafts
      have been used successfully to restore mandibular form, function and esthetics
      after extensive mandibular resection. In this article, we describe a case of a
      multiply recurrent ameloblastoma treated by left hemimandibulectomy and immediate
      reconstruction with a custom-fabricated alloplastic system in combination with an
      anterior iliac crest bone graft. The result was a high degree of mandibular
      function and facial cosmesis, minimal donor-site morbidity, and nearly immediate
      return to function. 

PMID- 25055229
TI  - Severe unilateral cross-bite secondary to tumour of the mandibular condyle.

PMID- 25055230
TI  - Managing patients with gingival graft failure or loss.

PMID- 25055231
TI  - Detection and prevention of oral cancer: are screening methods effective?

PMID- 25055232
TI  - Optimizing patient safety: can we learn from the airline industry?

PMID- 25055233
TI  - Silorane adhesive system: a case report.
AB  - Silorane-based composite resin requires a specific adhesive system: a 2-step self
      etching adhesive. Clinical protocols are well established and are based on the
      principles of adhesion to mineralized dental tissues. In this paper, we present a
      clinical application of the silorane adhesive system in a class-II restoration
      using silorane-based composite resin. 

PMID- 25055234
TI  - Uncertainty remains about effectiveness of antibiotic prophylaxis for bacterial
      endocarditis.

PMID- 25055235
TI  - Incidence of dental caries among susceptible community-dwelling older adults
      using fluoride toothpaste: 2-year follow-up study.
AB  - OBJECTIVES: To explore reasons for the underuse of dental services covered by a
      government-funded program in Alberta. METHODS: In 2011, a survey questionnaire
      was sent to 4000 randomly selected clients of the Alberta Child Health Benefit
      and the Alberta Adult Health Benefit programs. Only respondents with children
      were included in the analysis. Reasons were explored among those who indicated
      that their children did not receive any dental services in the year before the
      survey. Difficulties faced by those who reported receiving at least 1 dental
      service were also noted. RESULTS: Among 795 respondents, 597 had at least 1
      child. A total of 1303 children aged 1-19 years (mean age 11.79 years, standard
      deviation 4.2) were included in the analysis. Of these children, 443 (34.0%) had
      not received any covered dental services; the most common reason (50.7%) was no
      perceived need (interpreted from the replies "my child was too young" or "had no
      dental problems") followed by perceived insufficient coverage (38.6%). The most
      common challenge reported by dental care users was also insufficient coverage
      (44.9%). About 57% of parents were aware that annual fluoride application was
      covered by the program; however, only 34.3% of their children received fluoride
      and 14.2% had sealants. CONCLUSIONS: Low-income families underuse available
      dental benefits for children. Perceived need seems to be the primary determinant
      of use. Parental awareness about the coverage does not seem to promote the use of
      preventive measures for young children.

PMID- 25055236
TI  - The importance of the initial comprehensive dental examination.
AB  - New diagnostic technology that improves patient care is becoming more common in
      dental practices at both the generalist and specialist levels. However, new
      diagnostic tests may be ordered prematurely or given more importance than
      warranted, resulting in misdiagnoses or delay of appropriate treatment. In this
      report, we describe a case in which several oral health care professionals failed
      to diagnose persistent facial pain correctly, in part because of failure to
      conduct a comprehensive dental examination and over-reliance on new technology.
      During 13 months of persistent mandibular pain, various diagnoses and treatments,
      the patient did not have a comprehensive dental examination-an examination that
      would have revealed periradicular periodontitis in tooth 25 causing the referred
      mandibular pain. This case demonstrates the importance and value of the initial
      comprehensive history and clinical examination, followed by conventional imaging
      to arrive at an accurate diagnosis and treatment plan. 

PMID- 25055237
TI  - Screening for oral potentially malignant epithelial lesions and squamous cell
      carcinoma: a discussion of benefit and risk.

PMID- 25055238
TI  - Barriers to utilization of dental services for children among low-income families
      in Alberta.
AB  - OBJECTIVES: To explore reasons for underutilization of dental services covered by
      a governmental funded program in Alberta. METHODS: A survey questionnaire was
      sent to 4,000 randomly selected clients of Alberta Health Benefit program. Only
      respondents with children were included in the analysis. Reasons were explored
      among those who indicated that their children did not receive any dental services
      in the year prior to the survey (non-users). Difficulties faced by those who
      reported receiving at least one dental service (users) were also collected.
      RESULTS: Among 795 returned surveys, 597 had at least one child. A total of 1,303
      children aged 1 to 19 years (mean age = 11.79 years, SD = 4.2) were included in
      the analysis. Of the 1,303 children, 443 (34%) did not receive any covered dental
      services (non-users); the most common reason (50.7%) was 'no perceived need'
      labeled for the replies 'my child was too young or had no dental problems'
      followed by perceived insufficient coverage (38.6%). The most common challenge
      reported by the dental care users was also insufficient coverage (44.9%). About
      57% of parents were aware of the covered yearly fluoride application; however,
      only 34.3% of their children received fluoride and 14.2% had sealants.
      CONCLUSIONS: Low-income families underutilized available dental benefits for
      children. Perceived need seemed to be the primary determinant of utilization.
      Parental awareness about the coverage did not seem to promote the utilization of
      preventive measures for young children.

PMID- 25055239
TI  - Effects of income and dental insurance coverage on need for dental care in
      Canada.
AB  - OBJECTIVE: To estimate the strength of the associations among income, dental
      insurance coverage and need for dental care (both urgent and nonurgent) in
      Canada. METHODS: Multinomial logistic models were fit to data from the 2009
      Canadian Health Measures Survey to test unadjusted associations among household
      income, dental insurance coverage and the need for urgent and nonurgent dental
      care. Adjusted associations, controlling for socio-demographic variables (age,
      sex, immigration status, education and province of residence) and oral health
      habits (brushing, flossing and visits to the dentist) were also evaluated.
      RESULTS: In the unadjusted model, need for treatment was lower among people with
      dental insurance than among those without insurance coverage (for urgent
      treatment: odds ratio [OR] 0.76, 95% confidence interval [CI] 0.66-0.89; for
      nonurgent treatment: OR 0.59, 95% CI 0.50-0.70). In addition, there was an income
      gradient, whereby people with higher income had less need for dental treatment
      (for urgent treatment: OR 0.99, 95% CI 0.99-1.00; for nonurgent treatment: OR
      0.99, 95% CI 0.98-0.99). Controlling for socio-demographic and oral health
      variables decreased the magnitude of the association between dental insurance
      coverage and need for treatment (for urgent treatment: OR 0.80, 95% CI 0.68-0.95;
      for nonurgent treatment: OR 0.76, 95% CI 0.63-0.92). An interaction term between
      dental coverage and income was significant in relation to the need for nonurgent
      treatment: among lower-income individuals, having insurance slightly decreased
      the odds of needing nonurgent treatment, with this decrease in odds becoming
      greater for middle-income earners and even greater for high-income earners.
      CONCLUSION: Income-related inequality in need for dental care exists even in the
      presence of dental insurance coverage and good dental hygiene habits. These
      findings highlight the need for increased access to dental care for low-income
      populations and families living in poverty.

PMID- 25055240
TI  - 6-Perfluoroalkylated phenanthridines via radical perfluoroalkylation of
      isonitriles.
AB  - A simple and efficient approach to 6-perfluoroalkylated phenanthridines starting
      with readily prepared isonitriles and commercially available cheap perfluoroalkyl
      iodides as perfluoroalkyl radical precursors is described. Various 6
      perfluoroalkylated phenanthridines are obtained in moderate to excellent yields.
      The sequence comprises a perfluoroalkylation with concomitant arene formation. 

PMID- 25055241
TI  - Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal
      transition by reducing GSK-3 activity.
AB  - Cytotoxin-associated gene A (CagA) is an oncoprotein and a major virulence factor
      of H. pylori. CagA is delivered into gastric epithelial cells via a type IV
      secretion system and causes cellular transformation. The loss of epithelial
      adhesion that accompanies the epithelial-mesenchymal transition (EMT) is a
      hallmark of gastric cancer. Although CagA is a causal factor in gastric cancer,
      the link between CagA and the associated EMT has not been elucidated. Here, we
      show that CagA induces the EMT by stabilizing Snail, a transcriptional repressor
      of E-cadherin expression. Mechanistically we show that CagA binds GSK-3 in a
      manner similar to Axin and causes it to shift to an insoluble fraction, resulting
      in reduced GSK-3 activity. We also find that the level of Snail protein is
      increased in H. pylori infected epithelium in clinical samples. These results
      suggest that H. pylori CagA acts as a pathogenic scaffold protein that induces a
      Snail-mediated EMT via the depletion of GSK-3. 

PMID- 25055242
TI  - Electrochemical flow-based solution-solid growth of the Cu2O nanorod array:
      potential application to lithium ion batteries.
AB  - The catalyzed solution-liquid-solid (SLS) growth has been well developed to
      synthesize semiconductor nanowires with controlled diameters. The SLS growth
      occurs in the longitudinal direction of nanowires, due to the directional
      anisotropy driven by the metal catalysts where chemical precursors are
      introduced. In the present study, we report a selective, template-free, and
      environmentally-friendly electrochemical flow-based solution-solid
      (electrochemical flow-SS) growth of the Cu2O nanorod array. The anisotropy for
      directional growth without any catalysts is generated by the electrical field in
      a flowing electrolyte of ultra-dilute CuSO4. The filamentary anisotropy
      originates from electric field enhancement on pyramidal nanocrystals in the
      electrolyte of low ionic conductivity (13 MUS cm(-1)). The Cu2O and Cu nanorods
      are able to be selectively synthesized by controlling the electrolyte pH and
      oxygen dissolution into the electrolyte. The synthesized Cu2O nanorod array shows
      excellent electrochemical properties as an anode material for lithium-ion
      batteries; the specific capacities increase from 323 to 1206 mA h g(-1) during
      500 cycles. The capacity enhancement is due to the phase transformation from Cu2O
      to CuO, nano-restructuring of nanorods into fragmented nanoparticles, and the
      progressive generation of an electroactive polymeric gel-like layer on the
      surface of the nanoparticles. The electrochemical flow-SS growth of Cu2O nanorods
      is expected to contribute to further development of other functional nanorods. 

PMID- 25055243
TI  - Measuring uniocular fields of rotation: modified Goldmann perimetry versus Aimark
      perimetry.
AB  - AIM: The quantification of ocular rotation in clinical practice is important,
      with a number of methods of assessment. However, there is little consensus on
      which method is most reliable and a lack of comparative data for these methods.
      The aim of this study was to directly compare the modified Goldmann and Aimark
      methods in subjects with full ocular motility. METHODS: This was a prospective
      cross sectional study to compare the extent of uniocular fields of rotation
      measured by the Aimark and the modified Goldmann perimeters. The inclusion
      criteria were full ocular motility and unaided logMAR visions of 0.2 or better in
      each eye. The results for the four cardinal positions of gaze (right, left, up
      and down gaze) were analysed and comparisons made with Bland Altman analysis.
      RESULTS: 108 subjects were recruited. The mean ocular rotations for abduction,
      elevation, adduction and depression were 69.9 degrees +/-12.8 degrees ; 57.8
      degrees +/-12.6 degrees ; 61.6 degrees +/-10.1 degrees  and 68.6 degrees +/-10.5
      degrees  respectively for the Aimark and 54.4 degrees +/-8.6 degrees ; 47.3
      degrees +/-8.3 degrees ; 53.3 degrees +/-8.6 degrees  and 59.5 degrees +/-9.1
      degrees  respectively for the modified Goldmann. The Aimark recorded higher
      ocular rotations for all positions of gaze in comparison to the modified
      Goldmann. The Aimark method tested twelve axes per eye and the modified Goldmann
      tested 8 axes per eye. However the Aimark was quicker per axis (RE: 11.7+/-4.9
      seconds; LE: 11.5+/-5 seconds) in comparison to the modified Goldmann (RE: 13.4+/
      10.6 seconds; LE: 13.1+/-10.6 seconds). CONCLUSION: The results between the two
      tests are not interchangeable. The Aimark method measures greater ocular
      rotations with a supra-threshold compared to the Goldmann measures with a foveal
      threshold fixation target.

PMID- 25055245
TI  - Flavonoid detection in hydroethanolic extract of Pouteria torta (Sapotaceae)
      leaves by HPLC-DAD and the determination of its mutagenic activity.
AB  - It is well known that phytotherapy has grown in popularity in recent years.
      Because a drug cannot be administered without ensuring its effectiveness and
      safety, the standardization and regulation of phytotherapeutic drugs are required
      by the global market and governmental authorities. This article describes a
      simple and reliable high-performance liquid chromatography-diode array detection
      analysis method for the simultaneous detection of myricetin-3-O-beta-D
      galactopyranoside, myricetin-3-O-alpha-L-arabinopyranoside, and myricetin-3-O
      alpha-L-rhaminopyranoside present in the hydroethanolic extract (ethanol/H2O,
      7:3, v/v) of Pouteria torta. The mutagenic activity of the extract was evaluated
      on Salmonella typhimurium and by an in vivo micronucleus test on the peripheral
      blood cells of Swiss mice. The linearity, sensitivity, selectivity,
      repeatability, accuracy, and precision of the assay were evaluated. The
      analytical curves were linear and exhibited good repeatability (with a deviation
      of less than 5%) and demonstrated good recovery (within the 83-107% range). The
      results demonstrate that the hydroethanolic extract exhibited a mutagenic
      activity in both assays, suggesting caution in the use of this plant in folk
      medicine.

PMID- 25055246
TI  - Taming HIV-related inflammation with physical activity: a matter of timing.
AB  - Many sets of data indicate that HIV-infected individuals maintain a low level of
      chronic immune activation and inflammation even in the presence of effective
      antiretroviral therapy (ART). This residual immune activation seems to be
      associated with accelerated aging and an increased incidence of non-AIDS-defining
      illnesses. Several published studies suggest that physical activity is a
      beneficial nonpharmacological intervention to reduce chronic inflammation.
      However, currently available data on the potential benefits of regular physical
      exercises for HIV-infected individuals are limited. Nonetheless, increasing
      evidence suggests that the introduction of regular physical exercise in the
      clinical management of HIV-infected individuals may have a significant positive
      impact in reducing some of the long-term complications of both infection and ART.
      Based on a comprehensive review of the existing data, we propose that regular
      physical exercise should be further studied as a potential antiinflammatory,
      nonpharmacological approach to be used to treat HIV residual disease and non-AIDS
      defining illnesses in ART-treated HIV-infected individuals.

PMID- 25055247
TI  - Flow cytometric analysis of the physical and protein-binding characteristics of
      solid drug nanoparticle suspensions.
AB  - AIM: Oral and intramuscular sustained-release antiretroviral solid drug
      nanoparticles (SDNs) are in development but there is limited understanding of
      whether nanoparticles or dissolved drug predominate systemically. MATERIALS &
      METHODS: A flow cytometric method was developed to analyze SDNs in biological
      fluids such as plasma, including the putative formation of a protein corona.
      RESULTS: SDNs were found to be stable in plasma and could be observed using the
      techniques developed here. In addition, transferrin, fibrinogen and albumin were
      found to be associated with SDNs upon incubation. CONCLUSION: This methodology
      has enabled us to determine protein interactions of SDNs in solution without the
      requirement of separation from the matrix. This will enable further studies of
      their biological fate.

PMID- 25055248
TI  - Emotion-related personality traits and peer social standing: unique and
      interactive effects in cyberbullying behaviors.
AB  - This study investigated the unique and interactive effects of emotion-related
      personality traits (i.e., callousness and uncaring traits) and peer social
      standing (i.e., social preference and perceived popularity) on cyberbullying
      behaviors in preadolescents. A total of 529 preadolescents (247 boys, 46.69%)
      were recruited from an Italian middle school (Mage=12 years and 7 months; SD=1
      year and 2 months). The participants primarily consisted of Italian children
      (91.12%). A series of binary logistic regression analyses parted by gender were
      conducted to examine the main and interactive effects of self-reported emotion
      related variables and peer-reported social standing in the prediction of self
      reported cyberbullying behaviors, while controlling for cyber victimization and
      grade effects. In girls, an uncaring disposition was directly associated with
      cyberbullying behaviors, whereas in boys this association only emerged for those
      with low perceived popularity. Our results indicated that, in developing
      anti(cyber)bullying programs, school researchers and practitioners should jointly
      consider individual and contextual factors.

PMID- 25055249
TI  - A novel locally operated master-slave robot system for single-incision
      laparoscopic surgery.
AB  - PURPOSE: Single-incision laparoscopic surgery (SILS) provides more cosmetic
      benefits than conventional laparoscopic surgery but presents operational
      difficulties. To overcome this technical problem, we have developed a locally
      operated master-slave robot system that provides operability and a visual field
      similar to conventional laparoscopic surgery. MATERIAL AND METHODS: A surgeon
      grasps the master device with the left hand, which is placed above the abdominal
      wall, and holds a normal instrument with the right hand. A laparoscope, a slave
      robot, and the right-sided instrument are inserted through one incision. The
      slave robot is bent in the body cavity and its length, pose, and tip angle are
      changed by manipulating the master device; thus the surgeon has almost the same
      operability as with normal laparoscopic surgery. To evaluate our proposed system,
      we conducted a basic task and an ex vivo experiment. RESULTS: In basic task
      experiments, the average object-passing task time was 9.50 sec (SILS cross),
      22.25 sec (SILS parallel), and 7.23 sec (proposed SILS). The average number of
      instrument collisions was 3.67 (SILS cross), 14 (SILS parallel), and 0.33
      (proposed SILS). In the ex vivo experiment, we confirmed the applicability of our
      system for single-port laparoscopic cholecystectomy. CONCLUSION: We demonstrated
      that our proposed robot system is useful for single-incision laparoscopic
      surgery.

PMID- 25055250
TI  - An in-vitro study on corn-shaped balloon-enhanced thrombolysis.
AB  - BACKGROUND: Glossy balloons were used to enhance deep vein thrombolysis. However,
      thrombi tend to yield in the balloon dilatation due to their smooth surface. It
      may be preferable to enhance thrombolysis by using balloons with a rough surface,
      instead of balloons with a smooth surface. MATERIAL AND METHODS: Four rabbits
      were used for the experiment and 60 blood clot samples were obtained, and the
      samples were randomly separated into one control group and four balloon
      solubilised groups. Urokinase solution (5000 U/ml) was used as the thrombolytic
      drug. The balloon-solubilised groups were enhanced respectively by 1 atm and 2
      atm pressurised glossy balloons, and 1 atm and 2 atm pressurised corn-shaped
      balloons. Thrombolysis rates and residual rates for different granularities of
      blood clots were calculated for comparasion. RESULTS: Thrombolysis rates of the
      groups using corn-shaped balloons were higher than those of the groups using
      glossy balloons (p = 0.003 and p = 0.002). Residual rates of Phi >= 3.7 mm blood
      clots for the groups using corn-shaped balloons were lower than those for the
      groups using glossy balloons (p < 0.001 and p < 0.001). CONCLUSION: Balloons
      could be used to enhance thrombolysis; under the same balloon dilatation
      pressure, thrombolysis rates when using corn-shaped balloons are better than
      those when using glossy balloons.

PMID- 25055251
TI  - Donor management does make a difference.

PMID- 25055252
TI  - Reviewer assistance: our support efforts must continue!

PMID- 25055253
TI  - Radiologic features of injuries from the Boston Marathon bombing at three
      hospitals.
AB  - OBJECTIVE: The aim of this study is to describe the radiologic imaging findings
      of primary, secondary, tertiary, and quaternary blast injuries in patients
      injured in the Boston Marathon bombing on April 15, 2013. MATERIALS AND METHODS:
      A total of 43 patients presenting to three acute care hospitals and undergoing
      radiologic investigation within 7 hours of the time of the bombing on April 15,
      2013, were included in this study. The radiographic and CT features of these
      patients were evaluated for imaging findings consistent with primary, secondary,
      tertiary, and quaternary blast injury. RESULTS: There were no pulmonary or
      gastrointestinal manifestations of the primary blast wave on imaging. Secondary
      blast injuries identified on imaging included a total of 189 shrapnel fragments
      identified in 32 of the 43 patients. The shrapnel was identified most often in
      the soft tissues of the leg (36.5%), thigh (31.2%), and pelvis (13.2%). Imaging
      identified 125 ball bearings, 10 nails, one screw, 44 metal fragments, and nine
      other (gravel, glass, etc.) foreign bodies. CONCLUSION: Injuries from the Boston
      Marathon bombing were predominantly from the secondary blast wave and resulted in
      traumatic injuries predominantly of the lower extremities. The most common
      shrapnel found on radiologic evaluation was the ball bearing.

PMID- 25055254
TI  - Spinal cord injuries with normal postmortem CT findings: a pitfall of virtual
      autopsy for detecting traumatic death.
AB  - OBJECTIVE: The purpose of this study was to assess the incidence of spinal cord
      injuries without radiographic abnormalities (SCIWORA) on postmortem MDCT studies
      and to characterize this entity in detail. MATERIALS AND METHODS: Data from
      consecutive autopsies from October 2009 through December 2012 were searched,
      yielding 30 cases of cervical spinal cord injuries. Two board-certified
      radiologists interpreted postmortem MDCT images acquired before autopsy. Cases
      with normal findings were defined as SCIWORA. RESULTS: Postmortem MDCT images in
      6 of 30 cases (20%; 95% CI, 8-39%) met SCIWORA criteria. In all these cases,
      traumatic death was not apparent before CT, the highest injury level was below
      C3, and fractures were not identified at autopsy. All subjects had occult disk
      injuries and perivertebral hemorrhage. Potentially fatal CT-detectable injuries
      to other parts of the body were not seen in five of six SCIWORA cases.
      CONCLUSION: A substantial proportion of fatal spinal cord injuries are without
      radiographic abnormalities at CT. Forensic radiologists and other interpreters of
      postmortem MDCT images must be aware of this entity to avoid excluding spinal
      cord injuries solely on the basis of postmortem MDCT findings. Special care is
      necessary in cases of unknown circumstances of death without abnormal CT
      findings. MRI may be used for further examination in the future, but until then,
      MDCT cannot replace autopsy for detecting SCIWORA.

PMID- 25055255
TI  - (18)F-FDG PET/CT of adrenal lesions.
AB  - OBJECTIVE: The purpose of this review is to describe FDG uptake characteristics
      of adrenal lesions, which can show increased FDG uptake on PET/CT. CONCLUSION:
      Both benign and malignant adrenal lesions can show increased FDG uptake.
      Knowledge of the uptake characteristics of these lesions is helpful for
      increasing diagnostic accuracy and expanding the differential diagnosis for
      adrenal lesions.

PMID- 25055257
TI  - PET/CT with (124)I-cG250: great potential and some open questions.
AB  - OBJECTIVE: A novel PET radiotracer, (124)I-cG250, is currently under clinical
      investigation to distinguish clear cell renal cell carcinoma from other benign
      and malignant renal masses. In this article, we will make suggestions on the data
      needed to maximize the use of this radiotracer. CONCLUSION: Although the
      published data are promising, further data are needed to assess the potential
      usefulness of this agent when dealing with indeterminate renal masses.

PMID- 25055256
TI  - Molecular targeted alpha-particle therapy for oncologic applications.
AB  - OBJECTIVE: A significant challenge facing traditional cancer therapies is their
      propensity to significantly harm normal tissue. The recent clinical success of
      targeting therapies by attaching them to antibodies that are specific to tumor
      restricted biomarkers marks a new era of cancer treatments. CONCLUSION: In this
      article, we highlight the recent developments in alpha-particle therapy that have
      enabled investigators to exploit this highly potent form of therapy by targeting
      tumor-restricted molecular biomarkers.

PMID- 25055258
TI  - Molecular imaging in oncology: (18)F-sodium fluoride PET imaging of osseous
      metastatic disease.
AB  - OBJECTIVE: This literature review details the history, pharmacokinetics, and
      utility of (18)F-sodium fluoride (Na(18)F) PET/CT in detecting osseous metastases
      compared with the current standard of care, technetium-99m methylene
      diphosphonate ((99m)Tc-MDP) bone scintigraphy. Additional discussion highlights
      solutions to impediments for broader implementation of this modality and insight
      into the complementary roles of (18)F-FDG PET/CT and Na(18)F PET/CT in oncology
      imaging, including preliminary data for combined Na(18)F and FDG PET/CT.
      CONCLUSION: Na(18)F PET/CT is the most comprehensive imaging modality for the
      evaluation of osseous metastatic disease. Although further data acquisition is
      necessary to expand cost-benefit analyses of this imaging agent, emerging data
      reinforce its diagnostic advantage, suggest methods to mitigate impediments to
      broader utilization of Na(18)F PET/CT, and introduce a potentially viable
      technique for single-session combined Na(18)F and FDG PET/CT staging of soft
      tissue and osseous disease.

PMID- 25055259
TI  - Journal Club: Diagnostic value of (18)F-FDG PET/CT and MRI in predicting the
      clinicopathologic subtypes of invasive breast cancer.
AB  - OBJECTIVE: The purpose of this study was to assess the diagnostic value of (18)F
      FDG PET/CT and MRI in predicting the clinicopathologic subtypes of breast cancer.
      MATERIALS AND METHODS: The cases of 89 patients with mass-type invasive breast
      cancer who underwent FDG PET/CT and MRI before therapy were retrospectively
      analyzed. Eight imaging variables-maximum standardized uptake value (SUVmax),
      apparent diffusion coefficient, size, shape, margin, intratumoral enhancement,
      dynamic kinetics, and high intratumoral signal intensity on T2-weighted images
      were compared with results for the pathologic markers Ki-67 antibody, estrogen
      receptor (ER), progesterone receptor (PR), and ERBB2 (formerly HER2 or HER2/neu).
      The diagnostic performance of the imaging variables for sub-typing was evaluated,
      and the predictors of the subtypes were elucidated. RESULTS: Higher SUVmax was
      significantly associated with a high Ki-67 index (p < 0.0001), ER-negative status
      (p = 0.0001), and PR-negative status (p = 0.047). Significant correlation was
      also found between size and ER status (p = 0.002) and between shape and PR status
      (p = 0.044). The AUC exceeded 0.7 only in identification of the luminal A sub
      type by application of cutoff values for SUVmax (AUC, 0.751). When smaller tumors
      were excluded, AUC increased (AUC, 0.803 for tumors > 16 mm). Multivariate
      analysis showed that SUVmax was the sole independent predictor of luminal A
      subtype (odds ratio per SD, 0.291; p < 0.0001). SUVmax was significantly lower
      for luminal A (4.4 +/- 2.2) than non-luminal A (8.1 +/- 4.4; p < 0.0001) tumors.
      A cutoff value of 5.4 yielded 79% sensitivity and 68% specificity for prediction
      that a tumor was the luminal A subtype. CONCLUSION: FDG PET/CT findings may
      contribute to differentiation of the luminal A and non-luminal A subtypes of
      invasive breast cancer.

PMID- 25055260
TI  - Initial radiographic features as outcome predictor of adult respiratory syncytial
      virus respiratory tract infection.
AB  - OBJECTIVE: The purposes of this study were to evaluate the chest radiographic
      features of adult patients hospitalized for respiratory syncytial virus
      respiratory tract infections and to assess whether initial chest radiographic
      findings help predict clinical outcome. MATERIALS AND METHODS: All adult patients
      hospitalized from January 2009 to December 2011 with laboratory-confirmed
      respiratory syncytial virus infection were included in the study. Patient
      clinical data and admission chest radiographs were retrospectively reviewed.
      Adverse outcomes included need for supplemental oxygen, need for assisted
      ventilation, and death. RESULTS: Of 285 patients (mean age, 74 +/- 16 years)
      included, 199 (69.8%) had abnormal chest radiographic findings: 49.5% (141/285)
      had acute changes, and 47.7% (136/285) had chronic changes. Consolidation (68/141
      [48.2%]) and ground-glass opacity (57/141 [40.4%]) were the predominant types of
      acute changes and were most common in unilateral single-lower-zone involvement.
      Consolidation, ground-glass opacity, and chronic changes occurred with
      significantly higher frequency in patients with adverse outcomes. The presence of
      acute (odds ratio, 3.6) and chronic (odds ratio, 2.2) changes were independent
      risk factors for mortality. CONCLUSIONS: A large proportion of adult patients
      hospitalized with respiratory syncytial virus respiratory tract infection had
      changes on initial chest radiographs. Consolidation or ground-glass opacity in a
      unilateral single-lower-zone distribution were the most common findings. The
      presence of acute and chronic radiographic lung changes was associated with
      adverse outcomes.

PMID- 25055261
TI  - Quantification of lung perfusion blood volume with dual-energy CT: assessment of
      the severity of acute pulmonary thromboembolism.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of
      quantification of lung perfused blood volume (PBV) with dual-energy CT (DECT) for
      assessment of the severity of acute pulmonary thromboembolism (PTE). MATERIALS
      AND METHODS: We retrospectively analyzed the records of 72 patients with PTE and
      168 without PTE who underwent DECT. The PTE patients were divided into high-,
      intermediate-, and low-risk groups based on clinical symptoms and right
      ventricular dysfunction. Correlations between quantification of whole-lung PBV
      and clinical severity were evaluated. Also evaluated was the relation between
      quantification of whole-lung PBV and right-to-left ventricular diameter ratio on
      CT images, which was used as an indicator of right ventricular dysfunction.
      RESULTS: In the PTE and control groups, the whole-lung PBVs were 27.6 +/- 7.9 and
      29.9 +/- 6.8 HU with a significant difference between them (p < 0.0281). In the
      high-, intermediate-, and low-risk PTE groups, the whole-lung PBVs were 16.0 +/-
      2.9, 21.0 +/- 4.2, and 31.4 +/- 5.8 HU with a significant difference between them
      (p < 0.05). There was no significant difference in whole-lung PBV between the
      control group and the low-risk PTE group, but there was a significant difference
      between the control group and the other two PTE groups. In PTE patients, whole
      lung PBV had negative correlation with right-to-left ventricular diameter ratio
      (R = -0.567, p < 0.001). CONCLUSION: Quantification of lung PBV with DECT is
      useful for assessment of the clinical severity of PTE and can be used as an
      indicator of right ventricular dysfunction.

PMID- 25055262
TI  - Potential for radiation dose savings in abdominal and chest CT using automatic
      tube voltage selection in combination with automatic tube current modulation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the simultaneous use of
      automatic tube current modulation (ATCM) and automatic tube voltage selection
      (ATVS) for abdominal and chest CT examinations regarding radiation dose reduction
      and image quality. MATERIALS AND METHODS: We enrolled 617 patients who all
      underwent contrast-enhanced chest or abdominal CT and divided them into two
      groups. In group A, 317 patients who underwent CT with only ATCM and a fixed body
      mass index-adjusted tube voltage (120 kV or 100 kV) were enrolled. In group B,
      both ATCM and ATVS were used. Image attenuation and noise were measured in
      different anatomic regions. RESULTS: The mean contrast-to-noise ratio and the
      signal-to-noise ratio of abdomen and chest CT was higher in group B compared with
      group A (p < 0.0001). In total, the effective radiation doses for abdomen and
      chest CT examinations were significantly reduced in group B by 18% compared with
      group A (p < 0.0001). When only examining those who benefited from the ATVS tool,
      a dose reduction of 35% for chest CT and 42% for abdomen CT could be achieved (p
      < 0.0001 for each). CONCLUSION: The simultaneous use of ATVS and ATCM enables
      significant radiation dose reduction in abdominal and thoracic contrast-enhanced
      CT examinations compared with the use of ATCM alone.

PMID- 25055263
TI  - Comparison of MRI pulse sequences for prediction of size of hepatocellular
      carcinoma at explant evaluation.
AB  - OBJECTIVE: The purpose of this study was to retrospectively compare the size of
      hepatocellular carcinoma (HCC) on images obtained using different MRI pulse
      sequences with the tumor size determined at pathologic evaluation of liver
      explant specimens. MATERIALS AND METHODS: Ninety-two patients with HCC who
      underwent contrast-enhanced liver MRI within 90 days before liver transplant were
      included. A single pathologist measured the dominant HCC in each case. In
      different sessions, two abdominal radiologists (readers 1 and 2) aware only of
      the location of the dominant HCC independently measured lesion size on images
      obtained using the following sequences: T2-weighted imaging; b-500 diffusion
      weighted imaging; and arterial, portal venous, and equilibrium phases of contrast
      enhancement. Size measurements on MR images were compared with explant
      measurements by use of Pearson correlation coefficients, paired t tests, and
      Bland-Altman plots. RESULTS: Correlation with pathologic findings was highest for
      reader 1 for portal venous (r = 0.890) and equilibrium (r = 0.828) phase images
      and for reader 2 for arterial, portal venous, and equilibrium phase images (r =
      0.842-0.860). Absolute error relative to pathologic size was lowest for reader 1
      using portal venous (4.3 mm) and for reader 2 using portal venous and arterial
      phase images (both 4.7 mm). Systematic error for both readers was lowest with
      portal venous and equilibrium phase images (reader 1, systematic under
      measurement of 0.5 mm in both sequences; reader 2, systematic over-measurement of
      0.1 mm with portal venous phase images and systematic under-measurement of 1.1 mm
      with equilibrium phase images). Sequences in which reader 1 made systematic over
      measurements were diffusion-weighted images, arterial phase images, and T2
      weighted images (by 3.5, 2.9, and 1.6 mm). Reader 2 made systematic over
      measurements using arterial phase and T2-weighted images (by 1.5 and 0.4 mm).
      CONCLUSION: The data suggest the arterial phase may be suboptimal for measuring
      HCC at MRI. Portal venous phase acquisition warrants further investigation as a
      potential standard approach for such measurements.

PMID- 25055264
TI  - Imaging and clinicopathologic features of esophageal gastrointestinal stromal
      tumors.
AB  - OBJECTIVE: The purpose of this article is to describe the imaging and
      clinicopathologic characteristics of esophageal gastrointestinal stromal tumors
      (GISTs) and to emphasize the features that differentiate esophageal GISTs from
      esophageal leiomyomas. MATERIALS AND METHODS: A pathology database search
      identified all surgically resected or biopsied esophageal GISTs, esophageal
      leiomyomas, and esophageal leiomyosarcomas from 1994 to 2012. Esophageal GISTs
      were included only if imaging studies (including CT, fluoroscopic, or (18)F-FDG
      PET/CT scans) and clinical data were available. RESULTS: Nineteen esophageal
      mesenchymal tumors were identified, including eight esophageal GISTs (42%), 10
      esophageal leiomyomas (53%), and one esophageal leiomyosarcoma (5%). Four
      patients (50%) with esophageal GIST had symptoms, including dysphagia in three
      (38%), cough in one (13%), and chest pain in one (13%). One esophageal GIST
      appeared on barium study as a smooth submucosal mass. All esophageal GISTs
      appeared on CT as well-marginated predominantly distal lesions, isoattenuating to
      muscle, that moderately enhanced after IV contrast agent administration. Compared
      with esophageal leiomyomas, esophageal GISTs tended to be more distal, larger,
      and more heterogeneous and showed greater IV enhancement on CT. All esophageal
      GISTs showed marked avidity (mean maximum standardized uptake value, 16) on PET
      scans. All esophageal GISTs were positive for c-KIT (a cell-surface transmembrane
      tyrosine kinase also known as CD117) and CD34. On histopathology, six esophageal
      GISTs (75%) were of the spindle pattern and two (25%) were of a mixed spindle and
      epithelioid pattern. Five esophageal GISTs had exon 11 mutations (with imatinib
      sensitivity). Clinical outcome correlated with treatment strategy (resection plus
      adjuvant therapy or resection alone) rather than risk stratification. CONCLUSION:
      Esophageal GISTs are unusual but clinically important mesenchymal neoplasms.
      Although esophageal GISTs and esophageal leiomyomas had overlapping imaging
      features, esophageal GISTs tended to be more distal, larger, more heterogeneous,
      and more enhancing on CT and were markedly FDG avid on PET. Given their malignant
      potential, esophageal GISTs should be included in the differential diagnosis of
      intramural esophageal neoplasms.

PMID- 25055265
TI  - Nonneoplastic, benign, and malignant splenic diseases: cross-sectional imaging
      findings and rare disease entities.
AB  - OBJECTIVE: Splenic lesions are commonly encountered and are often incidental in
      nature. Benign splenic vascular neoplasms include hemangioma, hamartoma,
      lymphangioma, extra-medullary hematopoiesis (EMH), and sclerosing angiomatoid
      nodular transformation (SANT). Uncommonly encountered entities of the spleen
      include focal EMH, focal myeloma, angiomyolipoma, and SANT. Primary splenic
      angiosarcoma is the most common malignant nonhematolymphoid malignancy of the
      spleen. Lymphoma, myeloma, and metastases are the other malignant entities
      involving the spleen. The clinical presentation, key imaging findings, and
      associations of benign, neoplastic, and malignant diseases that can involve the
      spleen will be discussed. CONCLUSION: Radiologists can use multimodality imaging
      to diagnose entities involving the spleen by recognizing key imaging features and
      considering patient characteristics. However, biopsy may be warranted for
      definitive diagnosis when imaging findings are nonspecific.

PMID- 25055266
TI  - Postoperative imaging of phalloplasties and their complications.
AB  - OBJECTIVE: In this article, we summarize the common phalloplasty indications,
      surgical techniques, and relevant anatomy. We review the appropriate imaging
      techniques used in postoperative evaluation of the neophallus and illustrate the
      postoperative appearance and complications associated with phalloplasty.
      CONCLUSION: Phalloplasty is an infrequently encountered yet complex procedure
      requiring careful postoperative imaging assessment. Modern microsurgical
      techniques have made free flaps the reference standard in phalloplasty, and the
      radiologist must be aware of the expected postoperative appearance and
      complications to appropriately manage these patients.

PMID- 25055267
TI  - Adrenal Incidentaloma triage with single-source (fast-kilovoltage switch) dual
      energy CT.
AB  - OBJECTIVE: The purpose of this article is to evaluate single-source dual-energy
      CT (DECT) for distinguishing benign and indeterminate adrenal nodules, with
      attention to the effects of phase of IV contrast enhancement. MATERIALS AND
      METHODS: A retrospective review revealed 273 contrast-enhanced abdominal DECT
      examinations from November 2009 through March 2012. Fifty adrenal nodules 0.8 cm
      or larger were identified in 41 patients (22 women and 19 men; average age, 66
      years; age range, 36-88 years). CT postprocessing and measurements were
      independently performed by two radiologists (readers 1 and 2) for each nodule, as
      follows: attenuation (in Hounsfield units) on true unenhanced images; contrast
      enhanced attenuation (in Hounsfield units) on monochromatic spectral images at
      40, 75, and 140 keV; and contrast-enhanced material density (in milligrams per
      milliliter) on virtual unenhanced images. Nodules were classified as benign (< 10
      HU) and indeterminate (>= 10 HU) according to true unenhanced images. RESULTS:
      Interreader agreement regarding benign and indeterminate nodules was high (kappa
      = 0.92; 95% CI, 0.8-1.0). At 140 keV, the attenuation of benign nodules was
      significantly lower (reader 1, 7.0 +/- 12.5 HU; reader 2, 7.8 +/- 9.2 HU) than
      that of indeterminate nodules (reader 1, 15.7 +/- 20.5 HU [p = 0.004]; reader 2,
      17.5 +/- 13.4 HU [p < 0.0001]). On virtual unenhanced images, benign nodules had
      significantly lower material density (reader 1, 992.4 +/- 9.9 mg/mL; reader 2,
      992.7 +/- 9.6 mg/mL) than did indeterminate nodules (reader 1, 1001.1 +/- 20.5
      mg/mL [p = 0.038]; reader 2, 1007.6 +/- 13.4 mg/mL [p < 0.0001]). CONCLUSION:
      DECT tools can mathematically subtract iodine or minimize its effects in high
      energy reconstructions, approximating unenhanced imaging and potentially reducing
      the need for additional studies to triage adrenal nodules detected on contrast
      enhanced DECT examinations.

PMID- 25055268
TI  - Model-based iterative reconstruction versus adaptive statistical iterative
      reconstruction in low-dose abdominal CT for urolithiasis.
AB  - OBJECTIVE: The purpose of this study was to determine whether there is added
      benefit to model-based iterative reconstruction as compared with adaptive
      statistical iterative reconstruction on low-dose abdominal CT in the clinical
      context of known or suspected urolithiasis. MATERIALS AND METHODS: Fifty-three
      consecutive patients (35 men, 18 women; mean [SD] age, 52.3 +/- 16.6 years)
      underwent unenhanced low-dose abdominal CT for detection or follow-up of urinary
      tract stones. Ureteral definition was evaluated subjectively by two blinded
      readers who scored it from 1 (excellent definition) to 4 (not distinguishable)
      and objectively by calculating contrast-to-noise ratio (CNR) for soft tissue and
      fat on a standard 40% adaptive statistical iterative reconstruction and on the
      corresponding model-based iterative reconstruction series. The position, maximal
      density, and diameter on the axial plane of stones were also evaluated on both
      series. RESULTS: There was an almost perfect agreement (kappa = 0.872) between
      readers for subjective evaluation of ureteral definition. The ureteral definition
      was significantly better for the model-based iterative reconstruction series
      (mean [SD] score, 1.998 +/- 0.839) compared with adaptive statistical iterative
      reconstruction (mean score, 2.536 +/- 0.799) (p < 0.0001). Mean CNR was
      significantly better on the model-based iterative reconstruction (17.82 +/- 4.84)
      compared with adaptive statistical iterative reconstruction (6.066 +/- 1.985) (p
      < 0.0001). Sixty-nine stones were found in total. Their maximal density measured
      from model-based iterative reconstruction was significantly higher (754.4 +/-
      376.5 HU) than that measured from adaptive statistical iterative reconstruction
      (559.4 +/- 352.4 HU) (p < 0.0001). Size of stones was overevaluated on model
      based iterative reconstruction (mean diameter, 4.91 +/- 2.61 mm) compared with
      adaptive statistical iterative reconstruction (4.52 +/- 2.63 mm) (p < 0.0001).
      CONCLUSION: Model-based iterative reconstruction of low-dose abdominal CT can
      offer significantly better ureteral definition than adaptive statistical
      iterative reconstruction, and its systematic use could thus be recommended.
      However, it has the tendency to systematically overevaluate the stones' densities
      and sizes.

PMID- 25055269
TI  - Preoperative assessment of prostate cancer using prebiopsy MRI.
AB  - OBJECTIVE: The purpose of this article is to retrospectively evaluate the impact
      of prebiopsy MRI on preoperative assessment of prostate cancer. MATERIALS AND
      METHODS: Between January 2005 and June 2012, 89 patients (mean age, 64 years;
      range, 50-77 years) underwent prebiopsy MRI, transrectal ultrasound-guided
      biopsy, and prostatectomy for adenocarcinoma. On MR images, prostate cancer was
      diagnosed if T2-weighted images, diffusion-weighted images, and dynamic contrast
      enhanced images were all positive. Preoperative cancers were classified as low,
      intermediate, high, and very high risk using prostate-specific antigen (PSA)
      level, biopsy Gleason score, or MRI tumor stage. Postoperative cancers were
      classified as low, intermediate, high, and very high risk using PSA level,
      prostatectomy Gleason score, and prostatectomy tumor stage. Interrater agreement
      using weighted kappa values was used to compare the paired data. RESULTS:
      Preoperative cancers assessed by PSA level alone and postoperative cancers were
      concordant in 24.7% (22/89) and discordant in 75.3% (67/89) of cases, with poor
      agreement (weighted kappa, 0.13; 95% CI, 0.05-0.21). Preoperative cancers
      assessed by biopsy Gleason score alone and postoperative cancers were concordant
      in 40.4% (36/89) and discordant in 59.6% (53/89) of cases, with fair agreement
      (weighted kappa, 0.22; 95% CI, 0.09-0.36). Preoperative cancers assessed by MRI
      tumor stage alone and postoperative cancers were concordant in 74.2% (66/89) and
      discordant in 25.8% (23/89) of cases, with moderate agreement (weighted kappa,
      0.54; 95% CI, 0.38-0.71). CONCLUSION: Prebiopsy MRI may provide better
      information on preoperative assessment of prostate cancer than PSA level and
      biopsy Gleason score.

PMID- 25055270
TI  - Bladder malignancies on CT: the underrated role of CT in diagnosis.
AB  - OBJECTIVE: The purpose of this article is to review the utility of CT in
      diagnosing bladder malignancies, CT protocol options that may improve the
      conspicuity of bladder tumors, suggestive imaging features, and potential mimics.
      CONCLUSION: Although evaluation of the bladder has traditionally been considered
      purely the realm of cystoscopy, many bladder tumors can be identified with CT.
      However, diagnosis requires optimization of CT technique and close attention to a
      number of potentially subtle findings.

PMID- 25055271
TI  - Radiology utilization in the emergency department: trends of the past 2 decades.
AB  - OBJECTIVE: The objective of our study was to assess radiology utilization trends
      for emergency department (ED) patients from 1993 through 2012. MATERIALS AND
      METHODS: For this retrospective study, we reviewed radiology utilization at a 793
      bed quaternary care academic medical center from January 1, 1993, through
      December 31, 2012, during which time the number of ED patient visits increased
      from approximately 48,000 to 61,000, and determined the number of imaging studies
      by modality (radiography, sonography, CT, MRI, other) and associated relative
      value units (RVUs). We used linear regression to assess for trends in the number
      of imaging RVUs and imaging accession numbers, our primary and secondary
      outcomes, respectively. RESULTS: The total RVUs attributable to ED imaging per
      1000 ED visits increased 208% from 1993 to 2007 (p < 0.0001) and then decreased
      24.7% by 2012 (p = 0.0019). The total number of imaging accession numbers per
      1000 ED visits increased 47.8% from 1993 until 2005 (p = 0.0003) and then
      decreased 26.9% by 2012 (p < 0.0001). CT RVUs per 1000 ED visits increased 493%
      until 2007 (p < 0.0001) and then decreased 33.4% (p < 0.0001), and MRI RVUs
      increased 2475% until 2008 (p < 0.0001) and then decreased 20.6% (p < 0.0032).
      Sonography RVUs increased 75.7% over the study period (p < 0.0001), whereas
      radiography RVUs decreased 28.1% (p = 0.0009). CONCLUSION: After a period of
      substantial increase from 1993 to 2007, volume-adjusted ED imaging RVUs declined
      from 2007 through 2012, largely because of the decreasing use of CT and MRI.
      Additional studies are needed to determine the causes of this decline, which may
      include quality improvement activities, advocacy for appropriateness by
      leadership, concerns regarding radiation exposure and cost, and health
      information technology interventions.

PMID- 25055273
TI  - Disparities in imaging utilization for acute ischemic stroke based on patient
      insurance status.
AB  - OBJECTIVE: Previous studies have shown socioeconomic disparities in imaging
      utilization for both acute and chronic diseases. We studied a nationwide database
      to determine whether insurance-based disparities exist in the utilization of
      imaging for acute ischemic stroke. MATERIALS AND METHODS: Inpatients with a
      primary diagnosis of acute ischemic stroke from November 2005 through December
      2011 were identified from the Perspective database. Patients were stratified into
      four groups according to insurance status as follows: uninsured, Medicaid,
      Medicare, and private insurance. Utilization rates of head CT, perfusion CT, head
      MRI, noninvasive head angiography (including head CT angiography [CTA] and head
      MR angiography [MRA]), noninvasive neck angiography (including neck CTA and neck
      MRA), carotid ultrasound, and echocardiography were compared using a chi-square
      test. A multivariable logistic regression model adjusting for potential
      confounding variables was fit to determine the association between insurance
      status and imaging utilization. RESULTS: A total of 210,212 patients were
      included in this study: 10,396 patients (5.0%) were uninsured, 14,243 patients
      (6.8%) had Medicaid, 153,209 patients (72.9%) had Medicare, and 32,364 patients
      (15.4%) had private insurance. Even after we had controlled for confounding
      variables, significant disparities existed in imaging utilization. Compared with
      patients with private insurance, uninsured patients had significantly lower odds
      of noninvasive head angiography (odds ratio [OR] = 0.78, 95% CI = 0.74-0.81, p <
      0.0001), neck angiography (OR = 0.79, 95% CI = 0.76-0.83, p < 0.0001), and head
      MRI (OR = 0.77, 95% CI = 0.74-0.81, p < 0.0001). The same was true for Medicaid
      and Medicare patients. CONCLUSION: Disparities exist in the utilization of
      noninvasive head and neck imaging, MRI, and echocardiography for patients with
      acute ischemic stroke based on patient insurance status. More research is needed
      to understand these disparities.

PMID- 25055272
TI  - MRI-guided focused ultrasound surgery for uterine fibroid treatment: a cost
      effectiveness analysis.
AB  - OBJECTIVE. The purpose of this article is to evaluate the cost effectiveness of a
      treatment strategy for symptomatic uterine fibroids that uses MRI-guided focused
      ultrasound as a first-line therapy relative to uterine artery embolization (UAE)
      or hysterectomy. MATERIALS AND METHODS. We developed a decision-analytic model to
      compare the cost effectiveness of three first-line treatment strategies: MRI
      guided focused ultrasound, UAE, and hysterectomy. Treatment-specific short- and
      long-term utilities, lifetime costs, and quality-adjusted life years (QALYs) were
      incorporated, allowing us to conduct an incremental cost-effectiveness analysis,
      using a societal willingness-to-pay (WTP) threshold of $50,000/QALY to designate
      a strategy as cost effective. Sensitivity analyses were subsequently performed on
      all key parameters. RESULTS. In the base-case analysis, UAE as a first-line
      treatment of symptomatic fibroids was the most effective and expensive strategy
      (22.75 QALYs; $22,968), followed by MRI-guided focused ultrasound (22.73 QALYs;
      $20,252) and hysterectomy (22.54 QALYs; $11,253). MRI-guided focused ultrasound
      was cost effective relative to hysterectomy, with an associated incremental cost
      effectiveness ratio (ICER) of $47,891/QALY. The ICER of UAE relative to MRI
      guided focused ultrasound was $234,565/QALY, exceeding the WTP threshold of
      $50,000/QALY, therefore rendering MRI-guided focused ultrasound also cost
      effective relative to UAE. In sensitivity analyses, results were robust to
      changes in most parameters but were sensitive to changes in probabilities of
      recurrence, symptom relief, and quality-of-life measures. CONCLUSION. First-line
      treatment of eligible women with MRI-guided focused ultra-sound is a cost
      effective noninvasive strategy. For those not eligible for MRI-guided focused
      ultra-sound, UAE remains a cost-effective option. These recommendations integrate
      both the short- and long-term decrements in quality of life associated with the
      specific treatment modalities. 

PMID- 25055274
TI  - Variability of MDCT dose due to technologist performance: impact of
      posteroanterior versus anteroposterior localizer image and table height with use
      of automated tube current modulation.
AB  - OBJECTIVE: The purpose of this study was to determine MDCT dose variability due
      to technologist variability in performing CT studies. MATERIALS AND METHODS:
      Fifty consecutive adult patients who underwent two portal venous phase CT
      examinations of the abdomen and pelvis on the same 64-MDCT scanner between
      January and December 2011 were retrospectively identified. Tube voltage (kVp),
      tube current (mA), use of automated tube current modulation (ATCM), dose-length
      product (DLP), volume CT dose index (CTDIvol), table height, whether the
      localizer image was obtained using the posteroanterior or the anteroposterior
      technique, arm position, and number of overscanned slices were recorded. RESULTS:
      For a given patient, the total examination DLP difference comparing the two MDCT
      studies ranged from 0.1% to 238.0%. For the same patient, total examination DLP
      was always higher when the localizer image was obtained with the posteroanterior
      compared with the anteroposterior technique. When table position was closer to
      the x-ray source, patients appeared magnified in the posteroanterior localizer
      image (8-29%; average, 14%) and higher tube currents were selected with ATCM.
      Localizer technique, table height, arm position, number of overscanned slices,
      and technologist were all significant predictors of dose. CONCLUSION: Patient off
      centering closer to the x-ray source resulted in patient magnification in the
      posteroanterior localizer image, leading to higher tube currents with ATCM and
      increased DLP. Differences in technologist, arm position, and overscanning also
      resulted in dose variability.

PMID- 25055275
TI  - The effect of image processing on the detection of cancers in digital
      mammography.
AB  - OBJECTIVE. The objective of our study was to investigate the effect of image
      processing on the detection of cancers in digital mammography images. MATERIALS
      AND METHODS. Two hundred seventy pairs of breast images (both breasts, one view)
      were collected from eight systems using Hologic amorphous selenium detectors: 80
      image pairs showed breasts containing subtle malignant masses; 30 image pairs,
      biopsy-proven benign lesions; 80 image pairs, simulated calcification clusters;
      and 80 image pairs, no cancer (normal). The 270 image pairs were processed with
      three types of image processing: standard (full enhancement), low contrast
      (intermediate enhancement), and pseudo-film-screen (no enhancement). Seven
      experienced observers inspected the images, locating and rating regions they
      suspected to be cancer for likelihood of malignancy. The results were analyzed
      using a jackknife-alternative free-response receiver operating characteristic
      (JAFROC) analysis. RESULTS. The detection of calcification clusters was
      significantly affected by the type of image processing: The JAFROC figure of
      merit (FOM) decreased from 0.65 with standard image processing to 0.63 with low
      contrast image processing (p = 0.04) and from 0.65 with standard image processing
      to 0.61 with film-screen image processing (p = 0.0005). The detection of
      noncalcification cancers was not significantly different among the image
      processing types investigated (p > 0.40). CONCLUSION. These results suggest that
      image processing has a significant impact on the detection of calcification
      clusters in digital mammography. For the three image-processing versions and the
      system investigated, standard image processing was optimal for the detection of
      calcification clusters. The effect on cancer detection should be considered when
      selecting the type of image processing in the future. 

PMID- 25055276
TI  - Imaging current spine hardware: part 1, cervical spine and fracture fixation.
AB  - OBJECTIVE: The goals of this article are to review the indications for use, the
      materials, and the designs of hardware more commonly used in the cervical spine;
      to discuss alternatives for each of the different types of hardware; to review
      normal postoperative imaging findings; to describe the appropriateness of
      different imaging modalities for postoperative evaluation; and to illustrate
      examples of hardware complications. This article will also review vertebral body
      fracture fixation. CONCLUSION: Stabilization and fusion of the spine with
      intervertebral disk replacement, artificial ligaments, spinous process
      distraction devices, plate-and-rod systems, dynamic posterior fusion devices, and
      implants composed of new types of material are increasingly more common in the
      contemporary surgical practice. These spinal hardware devices will be seen more
      often in radiology practice. Successful postoperative radiologic evaluation of
      spinal hardware necessitates an understanding of the fundamental design of the
      hardware, the physiologic objective of the hardware, normal and abnormal
      postoperative imaging appearances, and complications unique to the hardware.

PMID- 25055277
TI  - MRI findings of rotator cuff myotendinous junction injury.
AB  - OBJECTIVE: The purpose of this article is to describe the MRI features of rotator
      cuff myotendinous junction injuries. MATERIALS AND METHODS: We retrospectively
      identified MRI cases with myotendinous junction injury of the rotator cuff
      muscles and reviewed clinical, imaging, and surgical records. MR images were
      reviewed independently by two musculoskeletal radiologists to grade myotendinous
      junction injuries (strain, partial tear, or complete tear) and to assess for
      concurrent tendon tears (partial or full thickness) and bone changes (fracture or
      contusion). RESULTS: The final study group comprised 16 subjects. The mean age
      was 38 years, with a majority of men (56%). The left shoulder was affected in 56%
      of subjects, with the dominant upper limb affected in 50%. The mean time between
      symptoms and MRI was 19 days. Subjects reported heavy lifting (19%), landing on
      the arm after a fall (19%), or prior shoulder therapeutic injection (25%).
      Myotendinous junction injuries affected the infraspinatus muscle (50%), followed
      by the supraspinatus (31%), subscapularis (25%), and teres minor (19%) muscles.
      About one fifth of subjects presented with more than one muscle affected, and 94%
      did not present with tears of the corresponding tendons. Most myotendinous
      junction injuries were strains (80%), followed by partial tears (20%). No
      complete tears were identified. There was no correlation between myotendinous
      junction injury and the presence of bone changes or the presence of tendon tears
      (p > 0.05). CONCLUSION: Rotator cuff myotendinous junction injuries affect mostly
      the infra-spinatus and supraspinatus muscles, usually in a strain pattern and
      without tear of the corresponding tendon attachment.

PMID- 25055278
TI  - The clinical correlation of a new practical MRI method for grading cervical
      neural foraminal stenosis based on oblique sagittal images.
AB  - OBJECTIVE: The purpose of this study was to determine whether each grade in a new
      system suggested by Park et al. (Park system) to assess cervical neural foraminal
      stenosis validly correlates with the associated clinical findings and to evaluate
      the interobserver agreement in grading between two MRI readers. MATERIALS AND
      METHODS: We evaluated 166 patients (98 men and 68 women; mean age, 46 years) at
      our institution who underwent oblique sagittal MRI of the cervical spine. Using
      the new Park grading system, two radiologists evaluated the MRI findings for the
      presence and grade of cervical neural foraminal stenosis at the most narrow
      point. A neurosurgeon assessed the associated clinical manifestations. A positive
      neurologic manifestation of the cervical neural foraminal stenosis was defined as
      more than one positive neurologic clinical manifestation combined with more than
      one positive neurologic sign. Interobserver agreements between the two
      radiologists were analyzed using kappa statistics. Correlation coefficients (R)
      to assess the relationship between the grade and neurologic manifestations were
      calculated with nonparametric correlation analysis (Spearman correlation). The
      relationship between the assigned grade and the clinical manifestations was
      analyzed several ways: vertebrae level (C4-5, C5-6, or C6-7) and by age group (<
      46 years and >= 46 years). RESULTS: Among patients who were evaluated by each
      reader to be grade 0, only 19 (17%) and 20 patients (18%) showed positive
      neurologic manifestations, respectively, with most patients showing negative
      neurologic manifestations. Among the patients who were grade 2 and 3, one reader
      found all patients and the second reader found all but one patient (100% and 93%,
      respectively) to have positive neurologic manifestations. According to the
      correlation coefficients, each Park grade was moderately correlated with the
      associated neurologic manifestations, such that higher grades were associated
      with more severe clinical manifestations. If we consider grade 2 or 3 MRI
      findings positive for identifying positive neurologic manifestations, the
      sensitivities and specificities were 39.7% and 99.0% (reader 1) and 39.7% and
      99.0% (reader 2), respectively. CONCLUSION: The Park system, based on oblique
      sagittal MRI sections, provides a reliable and reproducible assessment of the
      severity of cervical neural foraminal stenosis. According to the Park system,
      grades 2 and 3 are associated with positive neurologic manifestations, and the
      Park system successfully predicts positive neurologic manifestations at these
      grades.

PMID- 25055279
TI  - Diagnostic utility of MRI and MR arthrography for detection of ligamentum teres
      tears: a retrospective analysis of 187 patients with hip pain.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic utility of MRI
      and MR arthrography for ligamentum teres tears in patients with hip pain.
      MATERIALS AND METHODS: This is a retrospective study involving 187 patients who
      underwent MRI or MR arthrography for hip pain. This study included 103 male and
      84 female patients with average age of 39 years. Three experienced
      musculoskeletal radiologists reviewed the MRI and MR arthrography studies to
      assess the ligamentum teres tears. The criteria for diagnosing normal or abnormal
      (i.e., ligament), partial or degenerative or complete tear of ligamentum teres
      were defined on the basis of several imaging characteristics. The MRI and MR
      arthrography results were correlated with arthroscopy, which served as the
      reference standard. Statistical analysis was performed to calculate the
      diagnostic yield, diagnostic accuracy, and diagnostic performance of MRI and MR
      arthrography in detecting partial or degenerative and complete ligamentum teres
      tears. Overall comparative performance of MRI and MR arthrography was assessed
      using Kruskal-Wallis test. RESULTS: For partial ligamentum teres tears, MRI
      showed lower sensitivity, specificity, and positive predictive value (0.41, 0.75,
      and 0.32, respectively) as compared to MR arthrography (0.83, 0.93, and 0.76,
      respectively), whereas the negative predictive value of MRI (0.82) was comparable
      to that of MR arthrography (0.95). No statistically significant difference (p <
      0.05) could be identified between MRI and MR arthrography for diagnosing complete
      ligamentum teres tears. CONCLUSION: Hip MRI is equally suited for diagnosis of
      complete ligamentum teres tears when compared with MR arthrography. By contrast,
      for partial or degenerative ligamentum teres tears, MR arthrography offers the
      advantage of better arthroscopic correlation.

PMID- 25055280
TI  - Prevalence of persistent falcine sinus as an incidental finding in the pediatric
      population.
AB  - OBJECTIVE: Persistence of the embryologic falcine sinus can be a congenital or
      acquired phenomenon related to a defect of the straight sinus. Previous studies
      have stated that it is rare for the falcine sinus to persist without an
      additional abnormality of the brain such as a vein of Galen malformation or
      venous sinus thrombosis. The purpose of this article is to show that persistent
      falcine sinus is not an uncommon isolated finding in the pediatric population.
      MATERIALS AND METHODS: We performed a retrospective review of pediatric brain
      MRIs to identify patients with a persistent falcine sinus and subsequently
      recorded whether there were findings in addition to the straight sinus defect.
      RESULTS: Thirty-one patients were identified as having a persistent falcine
      sinus, five of whom had no other congenital or acquired abnormality of the brain
      other than a defect in the straight sinus. CONCLUSION: Our data support the
      hypothesis that persistent falcine sinus is not an uncommon isolated finding in
      the pediatric population.

PMID- 25055281
TI  - Endovascular treatment of superior mesenteric artery pseudoaneurysms using
      covered stents in six patients.
AB  - OBJECTIVE: The objective of our study was to evaluate our experience with the use
      of endovascular treatments for superior mesenteric artery (SMA) pseudoaneurysms
      using covered stents. MATERIALS AND METHODS: Between 2002 and 2011, six patients
      (mean age, 41.7 years; range, 23-65 years) with SMA pseudoaneurysms were treated
      percutaneously with the placement of covered stents at our institution. The
      causes of SMA pseudoaneurysms were penetrating trauma (n = 2), blunt trauma (n =
      1), and previous surgical procedures (n = 3). The mean diameter of the SMA
      pseudoaneurysms was 16 mm (range, 4-24 mm). Technical success and clinical
      success were retrospectively analyzed. RESULTS: Immediate technical success,
      defined as exclusion of the pseudoaneurysm and lack of active extravasation, was
      achieved in all six patients. Secondary balloon angioplasty was needed in one
      patient with residual narrowing. There was a small dissection of the proximal SMA
      necessitating placement of a second bare stent across the dissection. A second
      covered stent (Fluency stent, 8 mm) was placed in the same patient because of
      recurrent bleeding due to a type II endoleak 5 days after the first covered stent
      had been placed. This patient had no subsequent episodes of bleeding or bowel
      ischemia. Follow-up CT in the remaining five patients (mean, 21 months; range, 1
      58 months) confirmed stent patency and preserved distal arterial flow to the
      bowel without episodes of bleeding or bowel ischemia during follow-up (mean, 27
      months; range, 11-58 months). CONCLUSION: Percutaneous endovascular treatment
      using a covered stent may be a safe and feasible tool for SMA pseudoaneurysms.

PMID- 25055282
TI  - Accelerated balloon-occluded retrograde transvenous obliteration without
      indwelling balloon occlusion for gastric varices with small gastrorenal shunts
      using a terminal gelfoam plug.
AB  - OBJECTIVE: We performed balloon-occluded retrograde transvenous obliteration in
      three consecutive patients with small gastric varices without indwelling balloon
      catheter occlusion. Foam of 3% sodium tetradecyl sulfate mixed with iodized oil
      and room air was injected retrograde through the gastrorenal shunt, followed by a
      thick absorbable gelatin sponge (Gelfoam, Pfizer) plug under only 10-minute
      balloon occlusion. CONCLUSION: Because complete obliteration of gastric varices
      was achieved in all patients without any complications, our technique is
      considered to be safe and effective for small gastric varices.

PMID- 25055283
TI  - Current status of imaging-guided percutaneous ablation of breast cancer.
AB  - OBJECTIVE: The purpose of this article is to briefly describe the various
      techniques used for percutaneous ablation of breast cancer, their preliminary
      results, and their limitations. The techniques include thermotherapy
      (radiofrequency ablation, laser irradiation, microwave irradiation, and
      insonation with high-intensity focused ultrasound waves), cryotherapy, and
      irreversible electroporation. CONCLUSION: The techniques used for percutaneous
      ablation of breast cancer raise many questions and issues that must be addressed
      before percutaneous ablation can be adopted for the treatment of early breast
      cancer.

PMID- 25055284
TI  - Dense breasts: a review of reporting legislation and available supplemental
      screening options.
AB  - OBJECTIVE: The objectives of this article are to discuss the Mammography Quality
      Standards Act (MQSA) and what it means for patients, define breast density and
      explain how it is measured, review the new state-based legislation regarding the
      reporting of dense breast tissue directly to patients and the possibility of an
      adjunct screening examination, describe possible supplemental screening options
      and the advantages and disadvantages of each, and outline the current
      shortcomings and unanswered questions regarding new legislation. CONCLUSION:
      Breast density is now established as an independent risk factor for developing
      breast cancer irrespective of other known risk factors. Women with breast density
      in the upper quartile have an associated four to five times greater risk of
      developing breast cancer relative to women with breast density in the lower
      quartile. Many states have enacted or proposed legislation requiring
      mammographers to report to patients directly if they have dense breast tissue and
      recommend discussing the possibility of a supplemental screening examination with
      their physicians. However, there is currently no consensus as to whether a
      supplemental screening examination should be pursued or which modality to use.
      Possible supplemental screening modalities include ultrasound, MRI, digital
      breast tomosynthesis, and molecular breast imaging. The U.S. Food and Drug
      Administration recently approved an automated breast ultrasound system for
      screening whole-breast ultrasound in patients with dense breasts. However, many
      questions are still unanswered including the impact on morbidity and mortality,
      cost-effectiveness, and insurance coverage.

PMID- 25055285
TI  - Clinical evaluation of a mobile digital specimen radiography system for
      intraoperative specimen verification.
AB  - OBJECTIVE: Use of mobile digital specimen radiography systems expedites
      intraoperative verification of excised breast specimens. The purpose of this
      study was to evaluate the performance of a such a system for verifying targets.
      MATERIALS AND METHODS: A retrospective review included 100 consecutive pairs of
      breast specimen radiographs. Specimens were imaged in the operating room with a
      mobile digital specimen radiography system and then with a conventional digital
      mammography system in the radiology department. Two expert reviewers
      independently scored each image for image quality on a 3-point scale and
      confidence in target visualization on a 5-point scale. A target was considered
      confidently verified only if both reviewers declared the target to be confidently
      detected. RESULTS: The 100 specimens contained a total of 174 targets, including
      85 clips (49%), 53 calcifications (30%), 35 masses (20%), and one architectural
      distortion (1%). Although a significantly higher percentage of mobile digital
      specimen radiographs were considered poor quality by at least one reviewer (25%)
      compared with conventional digital mammograms (1%), 169 targets (97%), were
      confidently verified with mobile specimen radiography; 172 targets (98%) were
      verified with conventional digital mammography. Three faint masses were not
      confidently verified with mobile specimen radiography, and conventional digital
      mammography was needed for confirmation. One faint mass and one architectural
      distortion were not confidently verified with either method. CONCLUSION: Mobile
      digital specimen radiography allows high diagnostic confidence for verification
      of target excision in breast specimens across target types, despite lower image
      quality. Substituting this modality for conventional digital mammography can
      eliminate delays associated with specimen transport, potentially decreasing
      surgical duration and increasing operating room throughput.

PMID- 25055287
TI  - Basic CT parameters.

PMID- 25055288
TI  - Anterior mediastinal masses.

PMID- 25055289
TI  - FDG volumetric parameters and survival outcomes after definitive
      chemoradiotherapy in patients with recurrent head and neck squamous cell
      carcinoma.
AB  - OBJECTIVE: The purpose of this study was to establish the predictive value of
      (18)F-FDG parameters for overall survival in biopsy-proven recurrent head and
      neck squamous cell cancer (HNSCC) patients after definitive chemoradiotherapy.
      MATERIALS AND METHODS: We conducted a retrospective study including 34 patients
      with HNSCC who had biopsy-proven recurrence between April 2004 and March 2012 and
      underwent FDG PET/CT at our institution at the time of recurrence. Maximum
      standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume
      (MTV), and total lesion glycolysis (TLG) were measured. The primary outcome
      measure was overall survival. ROC analysis, univariate and multivariate Cox
      regression models, and Kaplan-Meir survival curves were performed. RESULTS: In
      univariate analyses, human papillomavirus (HPV) status (p = 0.04), primary site
      recurrence of MTV (p = 0.03), metastasis of MTV (p = 0.02), metastasis of TLG (p
      = 0.02), total MTV (p = 0.002), and total TLG (p = 0.04) were significantly
      associated with overall survival outcome. Total MTV remained as significant
      independent prognostic factor when adjusted for all other covariates except for
      primary site recurrence SUVmax and SUVpeak and lymph node SUVmax and SUVpeak.
      There was a significant difference in time to survival between patients with
      total MTV above and below the 50th percentile (Mantel-Cox log-rank test, p = 0.05
      and Gehan-Breslow-Wilcoxon test, p = 0.03) and the optimum threshold of 16.8 mL
      (Mantel-Cox log-rank test, p = 0.01 and Gehan-Breslow-Wilcoxon test, p = 0.01;
      hazard ratio [HR], 0.25). CONCLUSION: FDG PET/CT-based total MTV and clinical HPV
      status may be significant prognostic markers for overall survival of patients
      with recurrent HNSCC after definitive chemoradiotherapy.

PMID- 25055290
TI  - FDG PET/CT in the management of nasopharyngeal carcinoma.
AB  - OBJECTIVE: FDG PET/CT has a growing role in the diagnosis and management of
      nasopharyngeal carcinoma (NPC). FDG PET has greater efficacy for N and M staging
      than other modalities, which enables the treating oncologists to select the
      appropriate mode of treatment. FDG PET/CT helps in radiation therapy planning,
      provides valuable prognostic information, and is useful in the assessment of
      therapy response and in follow-up to detect recurrences. CONCLUSION: FDG PET/CT
      is a valuable imaging test in the management of NPC.

PMID- 25055291
TI  - Use of high-resolution volumetric MR spectroscopic imaging in assessing treatment
      response of glioblastoma to an HDAC inhibitor.
AB  - OBJECTIVE: Improved predictive imaging would enable personalization and
      adjustment of treatment, which are critical for patients with glioblastomain whom
      therapy is likely to fail. This article describes the use of MR spectroscopic
      imaging (MRSI) to predict early clinical and behavioral response to a therapy and
      an effort to develop high-resolution, volumetric MRSI to improve its clinical
      application. CONCLUSION: MRSI may enable quantitative analysis of brain tumor
      response, offering a precise tool for monitoring of patients in clinical trials.

PMID- 25055292
TI  - Low-normal lung volume correlates with pulmonary hypertension in fibrotic
      idiopathic interstitial pneumonia: computer-aided 3D quantitative analysis of
      chest CT.
AB  - OBJECTIVE: We investigated whether the lung volume determined on CT, especially
      the volume of the normal lung, is correlated with mean pulmonary artery pressure
      (PAP) in patients with chronic fibrosing idiopathic interstitial pneumonia (IIP).
      MATERIALS AND METHODS: The subjects were 40 patients with IIP who underwent right
      heart catheterization (RHC) and chest CT. Thirty-three patients (82.5%) were
      smokers or former smokers. Using a computer-aided system, the lungs in the 3D CT
      images were automatically categorized pixel-by-pixel with gaussian
      histogramnormalized correlations, and the relative volume of each lesion to the
      CT lung volume was calculated as "normal(%)," "ground-glass opacities(%),"
      "consolidation(%)," "emphysema(%)," and "fibrosis(%)." The relationship between
      each "volume(%)" and pulmonary hypertension was evaluated using logistic
      regression analysis. ROC curves were constructed to assess the predictive value
      of these CT-based volumes in the identification of pulmonary hypertension.
      RESULTS: Sixteen patients had pulmonary hypertension at rest (mean PAP > 25 mm Hg
      on RHC). Emphysema constituted more than 10% of the CT lung volume in 13
      patients. On multivariate analysis of each volume(%), normal(%) was significant
      for detecting pulmonary hypertension (odds ratio, 0.92; 95% CI, 0.86-0.96; p =
      0.02). On ROC analysis, the AUC of normal(%) was 0.849 (0.731-0.967). CONCLUSION:
      The relative CT volume of any single lesion was of limited value in predicting
      pulmonary hypertension in patients with pulmonary fibrosis and emphysema. In
      these patients, normal(%), measured by a 3D computer-aided system, was correlated
      with pulmonary hypertension measured by RHC.

PMID- 25055293
TI  - Renal remodeling after abdominal radiation therapy: parenchymal and functional
      changes.
AB  - OBJECTIVE: The purpose of this study was to quantify changes in renal length,
      volume, and function over time after upper abdominal radiation therapy. MATERIALS
      AND METHODS: Imaging and clinical data were retrospectively reviewed for 27
      adults with abdominal radiation therapy between 2001 and 2012. All had two
      kidneys, radiation exposure to one kidney, and survival of at least 1 year after
      therapy. Mean prescribed dose was 52 +/- 9 Gy to extrarenal targets. Length and
      volume of exposed and unexposed kidneys were measured on CT scans before
      treatment (baseline) and at intervals 0-3, 3-6, 6-12, 12-24, 24-36, and more than
      36 months after completion of radiotherapy. Serum creatinine was correlated at
      each interval. Mixed-models ANOVA was used to test renal length and volume, serum
      creatinine, and time against multiple models to assess for temporal effects;
      specific time intervals were compared in pairwise manner. RESULTS: Mean follow-up
      duration was 35 months (range, 5-94 months). Exposed kidney length and volume
      progressively decreased from baseline throughout follow-up, with mean loss of 23%
      (p < 0.001) and 47% (p < 0.001), respectively. Slight increase in unexposed
      kidney length was not significant. Mean serum creatinine increased from 0.86 +/-
      0.18 mg/dL at baseline to 1.12 +/- 0.27 mg/dL at 12-24 months (p < 0.001), then
      stabilized. CONCLUSION: Kidneys exposed to radiation during therapy of adjacent
      malignancies exhibited continuous progressive atrophy for the entire follow-up
      period, nearly 8 years. Volume changes were twice as great as length changes.
      Renal function also declined. To accurately interpret follow-up studies in cancer
      survivors, radiologists should be aware of the potential for progressive renal
      atrophy, even many years after radiation therapy.

PMID- 25055294
TI  - Comparison between arthroscopic findings and 1.5-T and 3-T MRI of oblique coronal
      and sagittal planes of the knee for evaluation of selective bundle injury of the
      anterior cruciate ligament.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic usefulness of
      combining oblique sagittal and oblique coronal MRI views of the anterior cruciate
      ligament (ACL) with traditional orthogonal views for the evaluation of selective
      bundle ACL injury and to evaluate whether there is a statistical difference in
      diagnostic ability between 1.5-T and 3-T MRI. MATERIALS AND METHODS: This
      retrospective study included 114 patients who underwent knee MRI (46 on 1.5 T and
      68 on 3 T) and arthroscopy at our institution. Two radiologists evaluated
      orthogonal views and ACL views on 1.5-T and 3-T MRI in variable combinations.
      They diagnosed ACL views as normal, entire ligament tear, anteromedial bundle
      tear, or posterolateral bundle tear. The surgeon then confirmed tears in the
      anteromedial or posterolateral bundle of the ACL arthroscopically if a selective
      bundle tear did exist. The arthroscopically confirmed diagnoses were used as the
      reference standard. The values were statistically analyzed. RESULTS: Sixty-seven
      percent of patients showed an ACL tear on arthroscopy, and 33% had a selective
      bundle tear; of these, 75% were anteromedial bundle tears and 25% were
      posterolateral bundle tears. On 1.5-T MRI, specificities of each view and
      combined views were the same (80%). The sensitivities and accuracies of the
      combined views were higher than the individual views; differences between
      individual views ranged from 4% to 15%. Reader 1 saw statistically significant
      differences between the oblique coronal and combined views. Although the
      performances of reader 2 showed similar results, the p values exceeded the
      critical value of statistical significance (0.063). On 3-T MRI, differences in
      specificities between the orthogonal and combined views and between the
      orthogonal and oblique coronal views were statistically significant (p, 0.016 and
      0.008 for readers 1 and 2, respectively). There were no significant differences
      in the diagnostic performance of 1.5-T and 3-T MRI. CONCLUSION: The oblique
      coronal view and the combination of the orthogonal view and both additional ACL
      views provide better diagnostic information with an improvement in specificity on
      3-T MRI compared with orthogonal views alone in the diagnosis of selective-bundle
      tears. Although diagnostic performance was not improved with the addition of the
      oblique views over orthogonal views on 1.5-T imaging, diagnostic performance was
      improved on 3-T MRI. Accuracies for individual imaging planes were not
      significantly different when comparing 1.5-T and 3-T MRI.

PMID- 25055295
TI  - Superolateral hoffa fat-pad edema and patellofemoral maltracking: predictive
      modeling.
AB  - OBJECTIVE: Superolateral Hoffa fat-pad edema is a frequent finding with patellar
      maltracking and may precede clinically significant chondrosis. The purpose of
      this study was to clarify which patellofemoral measurements are most highly
      associated and to develop a prediction rule to guide clinical decision making.
      MATERIALS AND METHODS: Twenty-three patellofemoral measurements were performed on
      71 knees retrospectively identified as having superolateral Hoffa fat-pad edema
      at MRI (Hoffa group) and on 45 normal knees (normal group). Univariate analysis
      was performed to examine the association between these measurements and Hoffa fat
      pad edema. Classification and regression tree analysis with 10-fold cross
      validation was used to generate a prediction model. RESULTS: For 16 of the 23
      patellofemoral measurements, there was a statistically significant difference (p
      < 0.05) between the Hoffa and normal groups. Classification and regression tree
      analysis identified a prediction model in which a patient is placed into the
      Hoffa group if one of three conditions is met: lateral patellar displacement
      greater than -3.6 mm and Insall-Salvati ratio greater than 0.99; lateral patellar
      displacement of -3.6 mm or less and Insall-Salvati ratio greater than 1.23; or
      lateral patellar displacement of -3.6 mm or less, Insall-Salvati ratio of 1.23 or
      less, and lateral trochlear inclination of 16.5 degrees  or less. In fitting of
      the original sample, this model had 91.6% sensitivity and 88.9% specificity for
      identifying the Hoffa group. When 10-fold cross validation was applied, the
      estimated generalizable sensitivity and specificity were 85.9% and 75.6%.
      CONCLUSION: Superolateral Hoffa fat-pad is strongly associated with a number of
      measures of patellar maltracking. A prediction model based on these measurements
      is accurate for differentiating knees with superolateral Hoffa fat-pad edema from
      normal knees.

PMID- 25055296
TI  - Ultrasound-guided fine-needle aspiration biopsy of internal mammary nodes:
      technique and preliminary results in breast cancer patients.
AB  - OBJECTIVE: The objective of our study was to describe our technique and
      preliminary results of ultrasound-guided fine-needle aspiration (FNA) of
      indeterminate internal mammary (IM) lymph nodes in patients with a history of
      breast cancer. CONCLUSION: Ultrasound-guided FNA of IM nodes is feasible and is
      particularly useful in the staging of breast cancer.

PMID- 25055297
TI  - Primary neuroendocrine carcinoma of the breast: clinical, imaging, and histologic
      features.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical, imaging, and
      histopathologic findings of primary neuroendocrine carcinoma of the breast.
      MATERIALS AND METHODS: A pathology database was searched for the records of
      patients with a histopathologic diagnosis of primary neuroendocrine carcinoma of
      the breast who had undergone mammography, sonography, or MRI between 1984 and
      2011. The imaging studies of eligible patients were retrospectively reviewed
      according to the BI-RADS lexicon, and clinical presentation and histopathologic
      characteristics were documented. Imaging characteristics were compared with
      historical controls of invasive mammary carcinoma. RESULTS: Eighty-seven patients
      (84 women, three men; mean age, 62.9 years; range, 28-89 years) were included in
      the study. The mean tumor size was 3.1 cm (range, 0.6-11 cm). Sixty-five of 84
      (77.4%) cancers were estrogen and progesterone receptor positive and ERBB2
      negative. A palpable mass (55.8%) was a common clinical manifestation. A high
      density, round or oval, or lobular mass with nonspiculated margins on mammograms
      and an irregular (65.4%), hypoechoic (78.4%) mass, with indistinct margins
      (43.5%), no or enhanced posterior acoustic features (77.9%) on sonograms were
      common findings. MRI revealed an irregular mass (83.3%), irregular margins
      (63.6%), and washout kinetics (85.7%). Neuroendocrine carcinoma presented more
      frequently as masses on mammograms. Calcifications were infrequent compared with
      their occurrence in invasive mammary cancer. CONCLUSION: Primary neuroendocrine
      carcinoma of the breast has mammographic features that differ from those of
      invasive mammary carcinoma. A round, oval, or lobular mass with nonspiculated
      margins, positive estrogen and progesterone receptor results, and negative ERBB2
      results should raise suspicion of primary neuroendocrine carcinoma.

PMID- 25055298
TI  - Medicolegal-malpractice and ethical issues in radiology. Fees for expert
      witnesses.

PMID- 25055299
TI  - SPR Child Abuse Committee Response regarding classic metaphyseal lesion.

PMID- 25055300
TI  - Reply: SPR Child Abuse Committee response regarding classic metaphyseal lesion.

PMID- 25055301
TI  - pH-induced conformational change of IscU at low pH correlates with
      protonation/deprotonation of two conserved histidine residues.
AB  - IscU, the scaffold protein for the major iron-sulfur cluster biosynthesis pathway
      in microorganisms and mitochondria (ISC pathway), plays important roles in the
      formation of [2Fe-2S] and [4Fe-4S] clusters and their delivery to acceptor apo
      proteins. Our laboratory has shown that IscU populates two distinct, functionally
      relevant conformational states, a more structured state (S) and a more dynamic
      state (D), that differ by cis/trans isomerizations about two peptidyl-prolyl
      peptide bonds [Kim, J. H., Tonelli, M., and Markley, J. L. (2012) Proc. Natl.
      Acad. Sci. U.S.A., 109, 454-459. Dai Z., Tonelli, M., and Markley, J. L. (2012)
      Biochemistry, 51, 9595-9602. Cai, K., Frederick, R. O., Kim, J. H., Reinen, N.
      M., Tonelli, M., and Markley, J. L. (2013) J. Biol. Chem., 288, 28755-28770].
      Here, we report our findings on the pH dependence of the D ? S equilibrium for
      Escherichia coli IscU in which the D-state is stabilized at low and high pH
      values. We show that the lower limb of the pH dependence curve results from
      differences in the pKa values of two conserved histidine residues (His10 and
      His105) in the two states. The net proton affinity of His10 is about 50 times
      higher and that of His105 is 13 times higher in the D-state than in the S-state.
      The origin of the high limb of the D ? S pH dependence remains to be determined.
      These results show that changes in proton inventory need to be taken into account
      in the steps in iron-sulfur cluster assembly and transfer that involve
      transitions of IscU between its S- and D-states. 

PMID- 25055302
TI  - Ru[(bpy)2(dppz)]2+ and Rh[(bpy)2(chrysi)]3+ targeting double strand DNA: the
      shape of the intercalating ligand tunes the free energy landscape of
      deintercalation.
AB  - Octahedral metal complexes can bind to double strand (ds) DNA either by
      intercalation or by insertion, this latter mechanism being observed in the case
      of mismatched base pairs (bps). In this work we modeled the process of
      deintercalation from the major groove for Delta-Ru[(bpy)2(dppz)](2+) (1) and
      Delta-Rh[(bpy)2(chrysi)](3+) (2), prototypical examples of metallo-intercalators
      and metallo-insertors, respectively. By using advanced sampling techniques, we
      show that the two complexes have comparable deintercalation barriers and that in
      both systems the main cost of deintercalation is due to disruption of pi-pi
      stacking interactions between the intercalating moiety and the bps flanking the
      binding site. A striking difference between dppz and chrysi is found in their
      intercalation modes, being their longest axes, respectively, perpendicular and
      parallel to the P-P direction between opposite DNA strands. This leads the two
      ligands to deintercalate from the DNA through different mechanisms. Compound 1
      goes through the formation of a metastable short-lived intermediate, with an
      overall free energy barrier of ~14.5 kcal/mol, in line with experimental
      findings. Due to the length of the dppz intercalating moiety, an extended plateau
      appears in the free energy landscape at ~3 kcal/mol above the most stable
      minimum. Compound 2 must cross a similar barrier (~15.5 kcal/mol), but does not
      form intermediates along the deintercalation path, and the deintercalation
      profile is steeper than that found for 1. Thus, the shape of the intercalating
      moiety affects the deintercalation mechanism of these inorganic molecules. This
      work is a first step to rationalize from a computational perspective the factors
      tuning the preferential binding mode of inorganic molecules (such as diagnostic
      probes, therapeutic agents, or regulators of DNA expression) to ds DNA.

PMID- 25055303
TI  - Terahertz spectra of biotin based on first principle, molecular mechanical, and
      hybrid simulations.
AB  - Terahertz (THz) absorption of biotin was simulated using the first principle and
      the density functional theory (DFT) both in the harmonic approximation and with
      corrections for the anharmonicity. Anharmonicity corrections were calculated
      using two different approaches. First, the perturbation theory-based first
      principle calculations were performed to include third- and fourth-order
      anharmonicity corrections in atomic displacements to harmonic vibrational states.
      Second, the atom-centered density matrix propagation molecular dynamics model
      that provides a good energy conservation was used to calculate the atomic
      trajectories, velocities, and a dipole moment time history of biotin at low and
      room temperatures. Predicted low-THz lines agree well with the experimental
      spectra. The influence of the polyethylene (PE) matrix embedment on the THz
      spectra of biotin at the nanoscale was studied using the developed hybrid
      DFT/molecular mechanical approach. While PE is almost transparent at THz
      frequencies, additional low-THz lines are predicted in the biotin/PE system,
      which reflects a dynamic interaction between biotin and a surrounding PE cavity. 

PMID- 25055304
TI  - Terahertz time-domain spectroscopy of human blood.
AB  - In the continuing development of terahertz technology to enable the determination
      of tissue pathologies in real-time during surgical procedures, it is important to
      distinguish the measured terahertz signal from biomaterials and fluids, such as
      blood, which may mask the signal from tissues of interest. In this paper, we
      present the frequency-dependent absorption coefficients, refractive indices, and
      Debye relaxation times of whole blood, red blood cells, plasma, and a thrombus. 

PMID- 25055305
TI  - Temperature-dependent terahertz imaging of excised oral malignant melanoma.
AB  - We imaged a single case of oral malignant melanoma using terahertz (THz)
      reflection imaging at room temperature (20  degrees C) and below freezing (-20 
      degrees C). A malignant nodule beneath the oral tissue surface was visualized
      using 2-D and B-scan THz imaging techniques. The THz images were well correlated
      with the histological findings. The nodule was found to have lower water content
      than that of normal cells, and this water effect may have influenced the THz
      refractive index and absorption coefficient at 20  degrees C. The THz
      spectroscopic image of the frozen tissue at -20  degrees C showed better contrast
      because of the lack of liquid water; this implies that there are significant
      structural differences between malignant oral melanoma cells and normal mucosal
      cells. The better contrast in the frozen tissue images was due to the greater
      penetration of THz radiation into the sample. This temperature-dependent THz
      imaging approach demonstrated the feasibility of accurate imaging of the oral
      tumor tissue. 

PMID- 25055307
TI  - Observation of hydrofluoric acid burns on osseous tissues by means of terahertz
      spectroscopic imaging.
AB  - Terahertz technologies have gained great amount of attention for biomedical
      imaging and tissue analysis. In this study, we utilize terahertz imaging to study
      the effects of hydrofluoric acid on both compact bone tissue and cartilage. We
      compare the differences observed in the exposure for formalin fixed and raw,
      dried, tissue as well as those resulting from a change in hydrofluoric (HF)
      concentration. Measurements are performed with THz-TDS, and a variety of
      spectroscopic-based image reconstruction techniques are utilized to develop
      contrast in the features of interest. 

PMID- 25055306
TI  - Development and testing of a single frequency terahertz imaging system for breast
      cancer detection.
AB  - The ability to discern malignant from benign tissue in excised human breast
      specimens in Breast Conservation Surgery (BCS) was evaluated using single
      frequency terahertz radiation. Terahertz (THz) images of the specimens in
      reflection mode were obtained by employing a gas laser source and mechanical
      scanning. The images were correlated with optical histological micrographs of the
      same specimens, and a mean discrimination of 73% was found for five out of six
      samples using Receiver Operating Characteristic (ROC) analysis. The system design
      and characterization is discussed in detail. The initial results are encouraging
      but further development of the technology and clinical evaluation is needed to
      evaluate its feasibility in the clinical environment. 

PMID- 25055308
TI  - Adaptive compressed sensing for the fast terahertz reflection tomography.
AB  - In this paper, an adaptive compressed sensing is proposed in order to enhance the
      performance of fast tetrahertz reflection tomography. The proposed method first
      acquires data at random measurement points in the spatial domain, and estimates
      the regions in each tomographic image where much degradation is expected. Then,
      it allocates additional measurement points to those regions, so that more data
      are acquired adaptively at the regions prone to degradation, thereby improving
      the quality of the reconstructed tomographic images. The proposed method was
      applied to the T-ray reflection tomography system, and the image quality
      enhancement by the proposed method, compared to the conventional method, was
      verified for the same number of measurement points. 

PMID- 25055309
TI  - Conceiving THz endometrial ablation: feasibility, requirements and technical
      challenges.
AB  - Shallow-ablation of endometrial lining using microwaves has been traditionally
      indicated as a minimally invasive treatment option for dysfunctional uterine
      bleeding (DUB). Known as microwave endometrial ablation (MEA), relevant procedure
      is used as an alternative to hysterectomy considering its safety, simplicity and
      effectiveness. In lieu of the prevailing MEA techniques, it is attempted in this
      study to foresee the possibility of conceiving an alternative and a newer option
      on endometrial ablation using mm-wave/THz frequencies. Commensurate with this
      motivated impetus, objectively considered are merits and design issues of using
      electromagnetic (EM) spectrum of mm-wave/THz region toward optimal conversion of
      EM energy into a thermal ablative source so that, the basal layer of endometrium
      can be effectively destroyed in surgical contexts as necessary. Hence, the
      feasibility of designing appropriate TEA applicators for controlled and safe
      procedures so as to ablate just the unwanted tissues within a localized zone of
      energy field is addressed. Lastly, a quantitative analysis on the interaction of
      THz EM-energy versus the lossy dielectric characteristics of endometrial medium
      is indicated to model the underlying (THz-energy)-to-(thermal energy)
      transduction. Relevant prospects of conceiving TEA and the associated pros and
      cons are identified specific to the prospects of feasibility, requirement
      considerations and technical challenges. 

PMID- 25055310
TI  - Automatic evaluation of the 30-s chair stand test using inertial/magnetic-based
      technology in an older prefrail population.
AB  - The aim of this study was to evaluate the inertial measures of the 30-s chair
      stand test using modern body-fixed motion sensors. Polynomial data fitting was
      used to correct the drift effect in the position estimation. Thereafter, the
      three most important test cycles phases ("impulse," "stand up," and "sit down")
      were characterized and automatically analyzed. Automated test control is
      provided, making it possible for researchers without engineering knowledge to run
      the test. A collection of meaningful data based on kinematic variables is
      selected for further research. The proposed methodology for data analysis is a
      feasible tool for use in clinical settings. This method may not only improve
      rehabilitation therapies but also identify people at risk for falls more
      accurately than simply evaluating the number of cycles. 

PMID- 25055311
TI  - Collection and analysis of a Parkinson speech dataset with multiple types of
      sound recordings.
AB  - There has been an increased interest in speech pattern analysis applications of
      Parkinsonism for building predictive telediagnosis and telemonitoring models. For
      this purpose, we have collected a wide variety of voice samples, including
      sustained vowels, words, and sentences compiled from a set of speaking exercises
      for people with Parkinson's disease. There are two main issues in learning from
      such a dataset that consists of multiple speech recordings per subject: 1) How
      predictive these various types, e.g., sustained vowels versus words, of voice
      samples are in Parkinson's disease (PD) diagnosis? 2) How well the central
      tendency and dispersion metrics serve as representatives of all sample recordings
      of a subject? In this paper, investigating our Parkinson dataset using well-known
      machine learning tools, as reported in the literature, sustained vowels are found
      to carry more PD-discriminative information. We have also found that rather than
      using each voice recording of each subject as an independent data sample,
      representing the samples of a subject with central tendency and dispersion
      metrics improves generalization of the predictive model. 

PMID- 25055312
TI  - A large-scale clinical validation of an integrated monitoring system in the
      emergency department.
AB  - We consider an integrated patient monitoring system, combining electronic patient
      records with high-rate acquisition of patient physiological data. There remain
      many challenges in increasing the robustness of "e-health" applications to a
      level at which they are clinically useful, particularly in the use of automated
      algorithms used to detect and cope with artifact in data contained within the
      electronic patient record, and in analyzing and communicating the resultant data
      for reporting to clinicians. There is a consequential "plague of pilots," in
      which engineering prototype systems do not enter into clinical use. This paper
      describes an approach in which, for the first time, the Emergency Department (ED)
      of a major research hospital has adopted such systems for use during a large
      clinical trial. We describe the disadvantages of existing evaluation metrics when
      applied to such large trials, and propose a solution suitable for large-scale
      validation. We demonstrate that machine learning technologies embedded within
      healthcare information systems can provide clinical benefit, with the potential
      to improve patient outcomes in the busy environment of a major ED and other high
      dependence areas of patient care. 

PMID- 25055313
TI  - Investigating the disagreement between clinicians' ratings of patients in ICUs.
AB  - We present a Bayesian analysis of ordinal annotations made by clinicians of
      patients in intensive care. In particular, we investigate the different ways in
      which clinicians can disagree and how their disagreement is reduced once they
      take part in a recently proposed procedure (INSIGHT) that aims at improving
      consistency. The model combines a nonparametric function (loosely interpretable
      as the health of the patient) with clinician-specific generative procedures for
      producing the observed ordinal values. Our analysis provides valuable details of
      the rating behavior of the individual clinicians and shows that the INSIGHT
      procedure is particularly effective at removing (some) clinician-specific
      inconsistencies and biases. 

PMID- 25055314
TI  - Semantic similarity measures in the biomedical domain by leveraging a web search
      engine.
AB  - Various researches in web related semantic similarity measures have been
      deployed. However, measuring semantic similarity between two terms remains a
      challenging task. The traditional ontology-based methodologies have a limitation
      that both concepts must be resided in the same ontology tree(s). Unfortunately,
      in practice, the assumption is not always applicable. On the other hand, if the
      corpus is sufficiently adequate, the corpus-based methodologies can overcome the
      limitation. Now, the web is a continuous and enormous growth corpus. Therefore, a
      method of estimating semantic similarity is proposed via exploiting the page
      counts of two biomedical concepts returned by Google AJAX web search engine. The
      features are extracted as the co-occurrence patterns of two given terms P and Q,
      by querying P, Q, as well as P AND Q, and the web search hit counts of the
      defined lexico-syntactic patterns. These similarity scores of different patterns
      are evaluated, by adapting support vector machines for classification, to
      leverage the robustness of semantic similarity measures. Experimental results
      validating against two datasets: dataset 1 provided by A. Hliaoutakis; dataset 2
      provided by T. Pedersen, are presented and discussed. In dataset 1, the proposed
      approach achieves the best correlation coefficient (0.802) under SNOMED-CT. In
      dataset 2, the proposed method obtains the best correlation coefficient (SNOMED
      CT: 0.705; MeSH: 0.723) with physician scores comparing with measures of other
      methods. However, the correlation coefficients (SNOMED-CT: 0.496; MeSH: 0.539)
      with coder scores received opposite outcomes. In conclusion, the semantic
      similarity findings of the proposed method are close to those of physicians'
      ratings. Furthermore, the study provides a cornerstone investigation for
      extracting fully relevant information from digitizing, free-text medical records
      in the National Taiwan University Hospital database. 

PMID- 25055315
TI  - A robust algorithm for segmenting and tracking clustered cells in time-lapse
      fluorescent microscopy.
AB  - We present herein a robust algorithm for cell tracking in a sequence of time
      lapse 2-D fluorescent microscopy images. Tracking is performed automatically via
      a multiphase active contours algorithm adapted to the segmentation of clustered
      nuclei with obscure boundaries. An ellipse fitting method is applied to avoid
      problems typically associated with clustered, overlapping, or dying cells, and to
      obtain more accurate segmentation and tracking results. We provide quantitative
      validation of results obtained with this new algorithm by comparing them to the
      results obtained from the established CellProfiler, MTrack2 (plugin for Fiji),
      and LSetCellTracker software. 

PMID- 25055316
TI  - Information theory-based automatic multimodal transfer function design.
AB  - In this paper, we present a new framework for multimodal volume visualization
      that combines several information-theoretic strategies to define both colors and
      opacities of the multimodal transfer function. To the best of our knowledge, this
      is the first fully automatic scheme to visualize multimodal data. To define the
      fused color, we set an information channel between two registered input datasets,
      and afterward, we compute the informativeness associated with the respective
      intensity bins. This informativeness is used to weight the color contribution
      from both initial 1-D transfer functions. To obtain the opacity, we apply an
      optimization process that minimizes the informational divergence between the
      visibility distribution captured by a set of viewpoints and a target distribution
      proposed by the user. This distribution is defined either from the dataset
      features, from manually set importances, or from both. Other problems related to
      the multimodal visualization, such as the computation of the fused gradient and
      the histogram binning, have also been solved using new information-theoretic
      strategies. The quality and performance of our approach are evaluated on
      different datasets. 

PMID- 25055317
TI  - Utility of a nonlinear joint dynamical framework to model a pair of coupled
      cardiovascular signals.
AB  - We have recently proposed a correlated model to provide a Gaussian mixture
      representation of the cardiovascular signals, with promising results in
      identifying rhythm disturbances. The approach provides a transformation of the
      data into a set of integrable Gaussians distributed over time. Looking into the
      model from a new joint modeling perspective, it is capable of assembling a
      filtered estimation, and can be used to derive temporal information of the
      waveforms. In this paper, we present a step-by-step derivation of the joint model
      putting correlation assumptions together to conclude a minimal joint description
      for a pair of ECG-ABP signals. We then probe novel applications of this model,
      including Kalman filter based denoising and fiducial point detection. In
      particular, we use the joint model for denoising and employ the denoised signals
      for pulse transit time (PTT) estimation. We analyzed more than 70 h of data from
      76 patients from the MIMIC database to illustrate the accuracy of the algorithm.
      We have found that this method can be effectively used for robust joint ECG-ABP
      noise suppression, with mean signal-to-noise ratio (SNR) improvement up to 23.2
      (12.0) dB and weighted diagnostic distortion measures as low as 2.1 (3.3)% for
      artificial (real) noises, respectively. In addition, we have estimated the error
      distributions for QT interval, systolic and diastolic blood pressure before and
      after filtering to demonstrate the maximal preservation of morphological features
      (DeltaQT: mean +/- std = 2.2 +/- 6.1 ms; DeltaSBP: mean +/- std = 2.3 +/- 1.9
      mmHg; DeltaDBP: mean +/- std = 1.9 +/- 1.4 mmHg). Finally, we have been able to
      present a systematic approach for robust PTT estimation (r = 0.98, p <; 0.001,
      mean +/- std of error = -0.26 +/- 2.93 ms). These findings may have important
      implications for reliable monitoring and estimation of clinically important
      features in clinical settings. In conclusion, the proposed framework opens the
      door to the possibility of deploying a hybrid system that integrates these
      algorithmic approaches for index estimation and filtering scenarios with high
      output SNRs and low distortion. 

PMID- 25055318
TI  - Random copolyesters containing perylene bisimide: flexible films and fluorescent
      fibers.
AB  - Random copolyesters of poly(l-lactic acid) (PLLA) and [poly(1,4
      cyclohexylenedimethylene-1,4- cyclohexanedicarboxylate)] (PCCD) incorporating
      varying mol ratios of perylene bisimide (PBI) were developed via a high
      temperature solution-blending approach. PCCD incorporating PBI was developed by
      melt polycondenzation followed by a polyester-polyester transesterification
      reaction between PCCD-PBI and PLLA. The polymers exhibited good solubility in
      common organic solvents and formed free-standing films, which showed bright red
      emission upon irradiation with ultraviolet radiation. A solid state fluorescence
      quantum yield of 10% was observed for this PBI based polyester, which was much
      higher than that reported in literature for PBI based polymers in the solid state
      (<1%). Strong red fluorescent nanofibers of these polymers were successfully
      constructed by electrospinning technique. A random copolyester incorporating
      donor based on oligo(p-pheneylenevinylene) (OPV) and PBI as acceptor chromophore
      was also synthesized and fluorescence microscopy images of the electrospun fibers
      of this polymer exhibited blue, green and red emission upon excitation at
      different wavelengths. The high temperature solution blending approach involving
      a high molecular weight polymer and a suitably functionalized pi conjugated
      molecule described here is a unique method by which 1D nanostructures of a wide
      range of pi-conjugated chromophores could be fabricated having strong
      fluorescence, with the scope of application in nanoscale optoelectronics,
      biological devices, as well as sensing. 

PMID- 25055319
TI  - Editor's note.

PMID- 25055320
TI  - From measuring the rural to the rural made to measure: social representations in
      perspective.
AB  - The founding myth of rural sociology established an opposition between
      countryside and cities, classifying these notions as separate spatial and social
      realities. In the last two decades, an idyllic and divinized image of the rural
      has been constructed, especially in countries from the European Union. What
      reasons have conspired to foster this new appreciation of the rural? Is there a
      mutually accepted, recurring meaning between the way this new discourse about the
      rural is created in Europe and in other countries? This study aims to explore
      some of the contradictions associated with what the authors call the emergence of
      a rural "made to measure" in a context marked by post-productivism and the
      increasing weight of post-materialist values, taking social representations of
      the rural as the focus of the analysis. 

PMID- 25055321
TI  - From application to implication in medical anthropology: political, historical
      and narrative interpretations of the world of sickness and health.
AB  - This article reviews some of the current writing on medical anthropology, and is
      guided by political orientation/implication in the choice of its study targets,
      its analysis and its construction of solutions for the problems investigated.
      Starting from the narratives of anthropologists, it goes on to show the
      historical and socio-political bases characteristic of the subject in their
      countries of origin or migration. Within a general overview of the three
      principal contemporary trends - critical medical anthropology, the anthropology
      of suffering and the anthropology of biopower - the focus is on theoretical and
      thematic choices to meet the demand for "politicization" of the anthropological
      debate in the field of health, on the basis of which an "implied" medical
      anthropology is advocated. 

PMID- 25055322
TI  - [Body, disability, and stigma in the origins of the field of adapted sport in the
      city of Buenos Aires, 1950-1961: a mere interiorization of a devalued identity?].
AB  - Although adapted sport is considered the main integrator of people with
      disabilities, Disability Studies argues that it reinforces the oppression
      suffered by this group. However, these positions do not historically reconstruct
      the ethos constructed in sport. In order to contribute to this discussion, I
      analyze here the ways of thinking about and experiencing disability that were
      constructed in the origins of the field of adapted sport, in the city of Buenos
      Aires, from 1950 to 1961. Thus, I begin by analyzing the content of publications
      of the first clubs for people with disabilities and in-depth interviews with
      protagonists of the origins of adapted sport and local physiatry. 

PMID- 25055323
TI  - [Potential and limits of evolutionary explanations of culture: a diachronic
      approach].
AB  - The aim of this article is to present some proposals concerning how broadly
      Darwinism can be applied to the realm of culture. Particular attention is paid to
      the models here called diachronic, which suggest the existence of patterns of
      cultural change over time according to the theory of natural selection. By means
      of a broader epistemological analysis, the relationship between an evolutionary
      explanation and a historical explanation is considered with a view to tracing the
      common features of the models in question and bringing to light their relative
      theoretical cogency and structural limitations. Finally, and more speculatively,
      potential areas for future research are indicated. 

PMID- 25055324
TI  - [The construction of cancer as an object of scientific study and sanitary problem
      in Argentina: discourses, experimental practices and institutional initiatives,
      1903-1922].
AB  - This article analyzes the construction of cancer as a sanitary problem and an
      object of scientific inquiry in Argentina in the first two decades of the
      twentieth century. It considers the acquisition and circulation of foreign
      knowledge on the subject, the context in which the first experimental
      developments arose, the institutional initiatives promoted by the medical
      profession and the way in which state authorities and civil society were enlisted
      to further these initiatives. There is a detailed examination of the process of
      creating the Instituto de Medicina Experimental, a center wholly devoted to the
      study and treatment of cancer, which was inaugurated in 1922, symbolically ending
      the first phase of constructing cancer as a problem in the country. 

PMID- 25055325
TI  - [Sociotechnical healthcare networks for acupuncture: a case study on the basic
      training of medical students].
AB  - This is a qualitative study on the sociotechnical networks that underlie the
      University of Sao Paulo School of Medicine's Acupuncture League. The actor
      network methodology, developed by Bruno Latour in studies on scientific
      productivity, is used. Consisting of field observations, semistructured
      interviews and a document analysis, the study presents relevant findings, with
      emphasis on understanding acupuncture as a therapeutic strategy effective in
      healthcare, modulating the use of drugs. It also identifies the need for
      regulation of the teaching and practice of acupuncture and recognition of other
      healthcare professionals as colleagues in the practice of this therapeutic
      method. 

PMID- 25055326
TI  - Disease and cure in Mozambican health service reports from the end of the
      nineteenth century.
AB  - In the late nineteenth century, health service reports constituted a repository
      of information on the main diseases in Mozambique and the impacts of their
      frequency, as well as on the procedures and methods used to fight disease within
      a regional framework whose description indicates a broad knowledge of the
      characteristics and potentials of the various districts and of the living
      conditions of the people. The objective of this article is to highlight that
      these reports constitute a privileged source not only for the study of the
      process of cementing Portuguese colonial rule in Mozambique, but also for the
      study of tropical medicine from a perspective that takes into account the
      specific conditions of the region, and which provides historical information on
      the analysis of the problems related to disease and cure. 

PMID- 25055327
TI  - The Botanic Mission to Mozambique (1942-1948): contributions to knowledge of the
      medicinal flora of Mozambique.
AB  - This article reviews the historical and scientific findings of the Botanic
      Mission to Mozambique (1942-1948) under the Tropical Botanic Garden of the
      Instituto de Investigacao Cientifica Tropical, in Lisbon, highlighting the
      collectors' field notes with the aim of identifying the traditional medicinal
      uses of Mozambican flora. Having collated information on 71 taxa (70 species and
      one genus), the medicinal usage of 34 species presumably not yet reported in
      Mozambique was identified, including five whose therapeutic use still had not yet
      been described in the African continent. Overall, 58 uses presumably not yet
      reported in Mozambique were recorded. 

PMID- 25055328
TI  - [Biomedical health care in Angola and in the Companhia de Diamantes de Angola,
      circa 1910-1970].
AB  - The scope of this paper is to analyze the provision of biomedical care in Angola
      during the activities of the Companhia de Diamantes de Angola. A comparative
      analysis of public health policies and practices of various colonial actors, such
      as the health services of the Company, its state counterpart and other colonial
      companies, will reveal differences in investment in health, namely in health
      facilities, personnel and treatment. This survey as well as the living conditions
      highlight the idiosyncratic and central nature of the health services of the
      Company in terms of morbidity and mortality in Angola, and the importance of
      these representations for a caregiving empire. 

PMID- 25055329
TI  - [Medical discourse and eating habits in the Hospital Real de Mocambique in the
      early nineteenth century].
AB  - Based on studies and archive documents, this work investigates the way European
      medical practice that interrelated diet and health in the early nineteenth
      century was transported to Africa, specifically Mozambique. The development of
      European theories about the preventive and therapeutic role of diet is examined,
      highlighting the conceptions of humoral theory and its reconfiguration by the
      science of the Enlightenment. The Mozambican hospital is described, taking into
      account the categories of patients cared for and prevailing diseases in the
      region. Focus is given to the changes introduced to hospital food to bring it
      closer to European habits. These changes are analyzed in the light of
      developments in European medical discourse about the body and foodstuffs,
      reconstructed by physiology and chemistry. 

PMID- 25055330
TI  - [The role of tropical medicine in the dissertations of the Porto school of
      medicine, 1875-1923].
AB  - Since 1827 the Escola Medico-Cirurgica of Porto published hundreds of inaugural
      dissertations dedicated to a broad range of subjects of medical nature. Bearing
      in mind the prevalence of the Lisbon school in the elaboration of its own
      scientific knowledge in the field of tropical medicine, the contribution of the
      Porto establishment may well be considered residual in comparative terms.
      However, between 1875 and 1923, there are documentary sources that address
      tropical diseases, particularly malaria. This work purports to show the
      contributions made by the Escola Medico-Cirurgica of Porto to a theme which
      initially did not arouse specific interest of northern Portuguese physicians,
      duly analyzing and defining the scientific output in the field of tropical
      medicine. 

PMID- 25055331
TI  - Public health and tropical modernity: the combat against sleeping sickness in
      Portuguese Guinea, 1945-1974.
AB  - Until the establishment of the "Commission for the study of and combat against
      sleeping sickness" (Missao de estudo e combate a doenca do sono) in 1945,
      underfunded and understaffed health services had not been a priority for the
      colonial administration in Portuguese Guinea. The Commission not only implemented
      endemic disease control in the territory under the auspices of metropolitan
      institutions, but also provided preventive public healthcare to the local
      population. Its relative success in reducing the negative impact of Human African
      Trypanosomiasis turned the colony into an apparent model of tropical modernity.
      In the process, the local evolution of the disease was marginalized, despite the
      tacit but contested recognition by some health professionals of the role of
      popular healthcare. 

PMID- 25055332
TI  - The historiographical approach taken in the nineteenth and twentieth centuries to
      the work of Jesuit doctors and apothecaries in the a Plata region in the
      eighteenth century.
AB  - The positions of Pedro Arata, Moises Santiago Bertoni, Carlos Leonhardt and
      Guillermo Furlong in the debate about the role of the Society of Jesus in the
      introduction and development of science in the La Plata region are investigated.
      Written between 1890 and the late 1950s, these authors' works not only analyze
      the medical, pharmaceutical and botanical knowledge of the Jesuit missionaries in
      the 1600s and 1700s, but also evaluate their contribution to scientific thinking
      in the countries colonized by Spain and Portugal. Their positions foretaste the
      historiographical debate about the reactionary nature of the Jesuit order and
      reflections about the contribution made by indigenous knowledge of American
      pharmacopeia to the knowledge the missionaries took to the continents where they
      were active. 

PMID- 25055333
TI  - [Epidemics in the news in Portugal: cholera, plague, typhus, influenza and
      smallpox, 1854-1918].
AB  - In severe health crisis like those of 1854-1856, 1899 and 1918, especially in
      Porto, where cholera morbus, the bubonic plague, typhus fever, pneumonic
      influenza and smallpox killed high percentages of the population, the images of
      the epidemics in the press enable us to identify the scientific knowledge in a
      country considered peripheral, but which had studies and personnel specialized at
      the most advanced levels for the time. A database of 6,700 news items and
      announcements reveals the medical and pharmaceutical knowledge of the second half
      of the nineteenth and early twentieth centuries, the way it was transmitted and
      disclosed to the public and the solutions offered by the health authorities.
      Hygiene was consistently highlighted in the news and announcements. 

PMID- 25055334
TI  - [Porto and the construction of the modern city: the case of Hospital Geral de
      Santo Antonio in the eighteenth and nineteenth centuries].
AB  - During a period of demographic and urban growth of the city of Porto, the need
      arose for a new hospital. The Santa Casa da Misericordia of Porto, in charge of
      erecting the new health facility, appointed the British architect John Carr to
      design the project. By means of the analysis of a set of archival sources and
      sundry literature on the topic, we examine the criteria chosen for the design and
      construction of Hospital Geral de Santo Antonio and if it fulfilled expectations,
      becoming a special space in the city. This article opens up a perspective on the
      study of the development of the city and the creation of this health facility,
      contributing to the historical trajectory of hospital architecture. 

PMID- 25055335
TI  - [The assistance of the Portuguese Colony of Brazil, 1918-1973].
AB  - This article seeks to redeem the historical memory of a health institution in
      Portugal which reconfigured itself and adapted to the social and medical needs
      and concerns during the twentieth century. The trajectory of this institution
      contributes to the history of Portuguese medicine and to the history of the
      philanthropy of the Portuguese colony resident in Brazil and the so called
      "Brazilians" that returned to Portugal, whose remittances provided the means to
      set up a benchmark health institution in the twenty-first century. The
      methodology was based on archival research in Portugal (Coimbra, Bissaya Barreto
      Foundation) and in Brazil (Rio de Janeiro, Real Gabinete Portugues de Leitura)
      and the cross-checking of these primary sources with due historical and social
      contextualization. 

PMID- 25055336
TI  - [Democracy and conflict in pluralist contexts: an interview with Chantal Mouffe].
AB  - Chantal Mouffe, along with Argentinian political theorist Ernesto Laclau (1935
      2014), laid down the bases of discourse theory in 1985. She later developed her
      work by exploring in more detail how discourse theory formulations influence the
      analysis of contemporary democracies. Approaching conflict as a product of the
      encounter with difference, Mouffe sees it as an indelible part of the
      constitution of social relationships. In this encounter with the author, we seek
      to reflect upon certain themes and problematics that are central to her work, and
      upon the implications of her theory for the field of contemporary education. 

PMID- 25055342
TI  - Design, synthesis and 3D-QSAR studies of new diphenylamine containing 1,2,4
      triazoles as potential antitubercular agents.
AB  - A new series of new diphenylamine containing 1,2,4-triazoles were synthesized
      from 4-arylideneamino-5-[2-(2,6-dichlorophenylamino) benzyl]-2H-1,2,4-triazole
      3(4H)-thiones 3a-f. The synthesized compounds were screened for in-vitro
      antimycobacterial and antibacterial activities. The synthesized compounds 4a, 4e
      and 4d have shown potential activity against Mycobacterium tuberculosis H37Rv
      strain with MIC of 0.2, 1.6 and 3.125 MUM respectively. To investigate the SAR of
      diphenylamine containing 1,2,4-triazole derivatives in more details, CoMFA (q(2)
      0.432, r(2)-0.902) and CoMSIA (q(2)-0.511, r(2)-0.953) models on M. tuberculosis
      H37Rv were established. The generated 3D-QSAR models are externally validated and
      have shown significant statistical results, and these models can be used for
      further rational design of novel diphenylamine containing 1,2,4-triazoles as
      potent antitubercular agents.

PMID- 25055343
TI  - Synthesised geriatric assessment in the Emergency Department setting: is it NEAT?
AB  - OBJECTIVE: To assess the time taken to complete a Synthesised Geriatric
      Assessment (SGA) in an Emergency Department (ED) and to determine what secondary
      patient characteristics affect results. METHODS: A convenience sample of 25
      patients aged over 65 from an Australian single-centre ED was used for this pilot
      study. Primary outcome measures included the overall time taken as well as the
      times for individual screening instruments. Data regarding patient
      characteristics were taken as secondary outcome measures to assess impact on
      times. For each of the screening instruments, the mean, median, interquartile
      range and the 90th percentile for the test duration was calculated. Linear
      regression was used to evaluate univariate associations between times and patient
      characteristics. P-values<0.05 were considered as statistically significant.
      RESULTS: Time required for completion of the SGA by 90% of the study population
      was 20 min and 40s. This represents approximately 8.6% of new 4-h ED targets.
      Secondary characteristics that affected the time taken for screening included
      patients from non-English-speaking backgrounds (P<0.05). CONCLUSIONS: Use of the
      SGA for intra-ED geriatric risk stratification is feasible and practical in the
      time-critical National Emergency Access Target (NEAT) environment. The relatively
      short amount of time used for screening this vulnerable demographic has
      implications for interdisciplinary management and potentially represents an
      efficient intervention to reduce future re-presentations and overcrowding in
      Australian EDs. Future high-quality trials are required to assess the clinical
      benefit of the SGA.

PMID- 25055344
TI  - Palladium(0)-catalyzed intramolecular decarboxylative allylation of ortho
      nitrobenzoic esters.
AB  - A Pd/Ag bimetallic system has been developed for the decarboxylative allylation
      of ortho-nitrobenzoic esters in an intramolecular fashion. In contrast to the
      typical sp(2)-sp(3) cross-coupling approach which requires air and moisture
      sensitive preformed organometallic reagents, we provide an alternative route to
      the synthesis of ortho-allyl nitroarenes from the corresponding ortho
      nitrobenzoic acid derivatives. The reaction proceeds through a mechanistically
      distinct decarboxylative metalation pathway. A cooperative reactivity of
      palladium and silver is crucial for the reaction outcome. 

PMID- 25055346
TI  - Height and drinking status in relation to risk of anemia in rural adult healthy
      Japanese men: the Nagasaki Islands study.
AB  - BACKGROUND: Several studies have reported that height is inversely associated
      with risk of cardiovascular disease but positively associated with cancer risk.
      On the other hand, evidence has been accumulating that anemia reflects poor
      health and increased vulnerability to poor outcomes in older persons. Moreover,
      alcohol consumption has also been reported to be associated with mortality.
      However, no studies have reported on a possible association between height and
      risk of anemia in relation to drinking status. METHODS: We conducted a cross
      sectional study of 1287 men aged 40-89 years undergoing general health check-ups.
      RESULTS: Independent from classic cardiovascular risk factors, we found a
      significant inverse association between height and anemia for non-drinkers and a
      J-shaped association for drinkers. The multivariable odds ratio (ORs) of an
      increment of 1 SD (standard deviation) in height (6.68 cm) for anemia for non
      drinkers was 0.59 (0.45-0.77). For drinkers, with the second quartile of height
      (Q2) as the reference group, the multivariable OR of anemia was 2.68(0.90-7.96)
      (p = 0.075) for the lowest height quartile (Q1), 2.73(0.92-8.08) for the third
      quartile (Q3) and 4.82(1.65-14.10) for the highest quartile (Q4) (p = 0.004).
      CONCLUSION: Height was found to be associated with anemia for rural Japanese men
      and drinking status is likely to affect those associations.

PMID- 25055345
TI  - An infectious bat-derived chimeric influenza virus harbouring the entry machinery
      of an influenza A virus.
AB  - In 2012, the complete genomic sequence of a new and potentially harmful influenza
      A-like virus from bats (H17N10) was identified. However, infectious influenza
      virus was neither isolated from infected bats nor reconstituted, impeding further
      characterization of this virus. Here we show the generation of an infectious
      chimeric virus containing six out of the eight bat virus genes, with the
      remaining two genes encoding the haemagglutinin and neuraminidase proteins of a
      prototypic influenza A virus. This engineered virus replicates well in a broad
      range of mammalian cell cultures, human primary airway epithelial cells and mice,
      but poorly in avian cells and chicken embryos without further adaptation.
      Importantly, the bat chimeric virus is unable to reassort with other influenza A
      viruses. Although our data do not exclude the possibility of zoonotic
      transmission of bat influenza viruses into the human population, they indicate
      that multiple barriers exist that makes this an unlikely event. 

PMID- 25055347
TI  - Impact of orange juice consumption on bone health of the U.S. population in the
      national health and nutrition examination survey 2003-2006.
AB  - Orange juice (OJ) fortified with calcium (Ca) and vitamin D has turned OJ into a
      readily available source of these nutrients for children and adults. However, the
      impact of OJ consumption on Ca and vitamin D adequacy and bone health has not
      been documented. The aim of this study was the evaluation of the contribution of
      100% OJ consumption to dietary and serum Ca and vitamin D status, and bone health
      parameters in the U.S. population aged 4 years and older (n=13,971) using the
      National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2005
      2006. Food consumption data were coded to produce micronutrient intake values
      using the USDA Food and Nutrient Database for Dietary Studies 3.0. Serum
      concentrations of bone-related micronutrients and biomarkers, bone mineral
      density (BMD), and bone mineral content (BMC) were measured. Analysis of data was
      conducted using SAS software 9.2 and SUDAAN. OJ consumers showed higher intakes
      of bone-related micronutrients, compared with nonconsumers (P<.05). In addition,
      OJ consumers had higher serum Ca levels in adults (P<.01) and had a lower odds
      ratio for serum 25-hydroxyvitamin D3 <20 ng/mL in children (P<.05). OJ
      consumption was positively associated with femur BMD in children (P<.05) and with
      femur BMC in both children and adults (P<.05). In conclusion, OJ may be
      recommended as an effective dietary means of improving the status of Ca and
      vitamin D, acid-base balance, and of promoting bone health in children and
      adults.

PMID- 25055348
TI  - Cognitive impairment in chronic kidney disease.

PMID- 25055349
TI  - Star fruit as a cause of acute kidney injury: a case report.

PMID- 25055350
TI  - Histological assessment of pre-implantation allograft biopsies: does it matters?

PMID- 25055351
TI  - Uremic serum inhibits in vitro expression of chemokine SDF-1: impact of uremic
      toxicity on endothelial injury.
AB  - INTRODUCTION: Endothelial dysfunction is important in the pathogenesis of
      cardiovascular disease (CVD) related to chronic kidney disease (CKD). Stromal
      cell-derived factor-1 (SDF-1) is a chemokine which mobilizes endothelial
      progenitor cells (EPC) and together with interleukin-8 (IL-8) may be used as
      markers of tissue injury and repair. OBJECTIVE: This study investigated in vivo
      and in vitro the effect of uremic media on SDF-1 and IL-8 expression. METHODS:
      Systemic inflammation was assessed by C-reactive protein (CRP) and interleukin-6
      (IL-6). IL-8 and SDF-1 were measured as markers of endothelial dysfunction and
      tissue repair, respectively, by ELISA. In vitro studies were performed on human
      umbilical vein endothelial cells (HUVEC) exposed to healthy or uremic media.
      RESULTS: The study included 26 hemodialysis (HD) patients (17 +/- 3 months on
      dialysis, 52 +/- 2 years, 38% men and 11% diabetic). Serum concentrations of CRP,
      IL-6, SDF-1 and IL-8 were 4.9 +/- 4.8 mg/ml, 6.7 +/- 8.1 pg/ml, 2625.9 +/- 1288.6
      pg/ml and 128.2 +/- 206.2 pg/ml, respectively. There was a positive correlation
      between CRP and IL-6 (rho = 0.57, p < 0.005) and between SDF-1 and IL-8 (rho =
      0.45, p < 0.05). In vitro results showed that after 6 hours treatment, SDF-1
      expression by HUVEC treated with uremic media is lower compared to cells treated
      with healthy media (p < 0.05). After 12 hours of treatment there was an increase
      in IL-8 when HUVECs were exposed to uremic media (p < 0.005). CONCLUSION: We
      suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of
      damage and subsequent vascular activation in uremia.

PMID- 25055352
TI  - Effect of vitamin D3 overdose and calcium supplementation in experimental
      nephrolithiasis model.
AB  - INTRODUCTION: There is little information in the literature relating
      supplementary oral usage of vitamin D and calcium to the development of kidney
      stones. OBJECTIVE: To evaluate the effect of high dose, 200 IU of vitamin D3 (V)
      with calcium supplementation (Ca). METHODS: Experimental model consists of
      insertion of pellets into the bladder of rats. V was administered for 30 days
      with or without Ca. The rats were divided in 6 groups: 1. Sham, 2. Pellets
      control; 3. V control; 4. Pellets + V; 5. Pellets + Ca and 6. Pellets + Ca + V.
      RESULTS: 50% and 17% decreases bladder stones formation in groups 5 and 6, p <
      0.005 comparing with the group 2 were observed. There was no hypercalcemia or
      hypercalciuria in all groups. We observed a significant decrease in calciuria in
      group 6 (p = 0.03). CONCLUSION: The administration of the V associated with Ca
      significantly decreased the formation of stones and caused a significant
      reduction in urinary calcium, suggesting a protection in the lithogenic
      pathophysiology.

PMID- 25055353
TI  - Standardization of renal function evaluation in Wistar rats (Rattus norvegicus)
      from the Federal University of Juiz de Fora's colony.
AB  - INTRODUCTION: There is great interest in the use of animal models in the study of
      renal pathophysiology requires standardization of parameters. OBJECTIVE:
      Standardize assessment of renal function in rats from in the Center for
      Reproductive Biology of Federal University of Juiz de Fora's colony. METHODS:
      Thirty Wistar rats were used and performed measurements of creatinine (serum and
      urine), serum urea and proteinuria. Were evaluated: the urine collection interval
      in metabolic cages (24 hours or 12 hours), the need for 12-hour fast, the need of
      urine and serum deproteinization for creatinine measurement, need of serum
      deproteinization in animals with acute kidney injury to a spectrophotometer and
      ELISA, and the comparison of 24-hour proteinuria (PT 24 hours) with the
      protein/creatinine ratio (rP/C). Means were compared by the Student's t test,
      Pearson correlation, Bland-Altman plot for agreement and linear regression model
      to estimate PT 24 hours from rP/C. RESULTS: The 24 hours urine output was greater
      than 12 hours, interfering with the creatinine clearance calculation. In the
      fasting group showed less water intake and lower urinary creatinine. There was
      great variability for the deproteinized whey and readings performed in the two
      devices were similar. There was a strong correlation between PT 24 hours and rP/C
      and the equation was generated: PT 24 hours = (8.6113 x rP/C) + 1.0869.
      CONCLUSION: Was standardized: 24-hour urine collection without fasting. The
      deproteinization showed no benefit. The measurements were performed with
      spectrophotometer reliability. It generated a practical formula for estimating PT
      24 hours through rP/C.

PMID- 25055354
TI  - Effect of standard and neutral-pH peritoneal dialysis solutions upon fibroblasts
      proliferation.
AB  - INTRODUCTION: Continuous exposition of the peritoneal membrane to conventional
      dialysis solutions is an important risk factor for inducing structural and
      functional alterations. OBJECTIVE: To compare in vitro mouse fibroblast NIH-3T3
      cell viability after exposition to a neutral pH dialysis solution in comparison
      to cells exposed to a standard solution. METHODS: Experimental study to compare
      the effects of a conventional standard or a neutral-pH, low-glucose degradation
      products peritoneal dialysis solution on the viability of exposed fibroblasts in
      cell culture. Both solutions were tested in all the commercially available
      glucose concentrations. Cell viability was evaluated with tetrazolium salt
      colorimetric assay. RESULTS: Fibroblast viability was significantly superior in
      the neutral pH solution in comparison to control, in all three glucose
      concentrations (Optical density in nm-means +/- SD: 1.5% 0.295 +/- 0.047 vs.
      0.372 +/- 0.042, p < 0.001; 2.3% 0.270 +/- 0.036 vs. 0.337 +/- 0.051, p < 0.001;
      4.25% 0.284 +/- 0.037 vs. 0.332 +/- 0.032, p < 0.001; control vs. neutral pH
      respectively, Student t Test). There was no significant difference in cell
      viability between the three concentrations of glucose when standard solution was
      used (ANOVA p = 0.218), although cell viability was higher after exposition to
      neutral pH peritoneal dialysis fluid at 1.5% in comparison to 2.3 and 4.25%
      glucose concentrations (ANOVA p = 0.008: Bonferroni 1.5% vs. 2.3% p = 0.033, 1.5%
      vs. 4.25% p = 0.014, 2.3% vs. 4.25% p = 1.00). CONCLUSION: Cell viability was
      better in neutral pH dialysis solution, especially in the lower glucose
      concentration. A more physiological pH and lower glucose degradation products may
      be responsible for such results.

PMID- 25055355
TI  - Depressed cardiac autonomic modulation in patients with chronic kidney disease.
AB  - INTRODUCTION: A dysfunctional autonomic nervous system (ANS) has also been
      recognized as an important mechanism contributing to the poor outcome in CKD
      patients, with several studies reporting a reduction in heart rate variability
      (HRV). OBJECTIVE: Evaluate the sympathovagal balance in patients with chronic
      kidney disease on conservative treatment. METHODS: In a cross-sectional study,
      patients with CKD stages 3, 4 and 5 not yet on dialysis (CKD group) and age
      matched healthy subjects (CON group) underwent continuous heart rate recording
      during two twenty-minute periods in the supine position (pre-inclined), followed
      by passive postural inclination at 70 degrees  (inclined period). Power spectral
      analysis of the heart rate variability was used to assess the normalized low
      frequency (LFnu), indicative of sympathetic activity, and the normalized high
      frequency (HFnu), indicative of parasympathetic activity. The LFnu/HFnu ratio
      represented sympathovagal balance. RESULTS: After tilting, CKD patients had lower
      sympathetic activity, higher parasympathetic activity, and lower sympathovagal
      balance than patients in the CON group. Compared to patients in stage 3, patients
      in stage 5 had a lower LFnu/HFnu ratio, suggesting a more pronounced impairment
      of sympathovagal balance as the disease progresses. CONCLUSION: CKD patients not
      yet on dialysis have reduced HRV, indicating cardiac autonomic dysfunction early
      in the course of CKD.

PMID- 25055356
TI  - Cognitive capacity in individuals with chronic kidney disease: relation to
      demographic and clinical characteristics.
AB  - INTRODUCTION: The life expectancy of individuals with Chronic Kidney Disease
      (CKD) on hemodialysis has increased, however, with over years in treatment, there
      is impairment of cognitive function that affect adherence to therapy and
      dialysis. OBJECTIVE: To evaluate the cognitive ability of individuals on
      hemodialysis through the Mini Mental State Examination (MMSE) and the relation to
      sociodemographic and clinical characteristics of these individuals. METHODS: We
      obtained demographic and clinical information of 75 individuals. To assess memory
      and cognition MMSE was applied, which was analyzed according to the different
      cutoff points proposed in the literature. After classifying the participants
      according to proposal of different studies, the causes of CKD and
      sociodemographic characteristics, individuals were divided into groups with and
      without cognitive impairment in an attempt to identify differences between them.
      RESULTS: Most participants were men with a mean age of 59.2 years. The mean MMSE
      score was 24.16 points and there was no difference (p < 0.05) in MMSE results
      between the different causes of CKD. MMSE scores were correlated (p < 0.05)
      positively with years of schooling and income and inversely with age. According
      to the different cutoff points, six to 34 participants showed cognitive
      impairment and memory, and only three of these were classified with cognitive
      impairment for all cutoff points evaluated. CONCLUSION: The average MMSE score
      declined with increasing age and increased with years of schooling and income per
      capita. No relationships were found to justify the harmful effects of dialysis
      process on cognition and memory.

PMID- 25055357
TI  - Left ventricular mass and cardiothoracic index in patients with chronic renal
      disease on hemodialysis.
AB  - INTRODUCTION: Left ventricular hypertrophy (LVH) is an independent predictor of
      cardiovascular risk in patients with chronic renal disease (CRD) on hemodialysis
      (HD). OBJECTIVE: To show the usefulness of chest radiography in the diagnosis of
      LVH in CRD patients on HD. METHODS: Cross-sectional study including 100 patients
      (58 men and 42 women), mean age 46.2 +/- 14.0 years, with CRD of all causes, for
      at least six months on HD. Were obtained echocardiogram and chest x-rays of
      patients, always up to one hour after the end of HD sessions. RESULTS: LVH was
      detected in 83 patients (83%), of whom 56 (67.4%) had the concentric pattern and
      27 (32.6%) with eccentric pattern of LVH. Cardiomegaly - defined by
      cardiothoracic index (CTI) > 0.5 - was present in 61 patients (61%). The
      following were the sensitivity, specificity and accuracy, respectively, for the
      variable ICT: 66.2%, 70.5% and 68.0%. The Pearson correlation between ICT and
      index of left ventricular mass (LVMI) was 0.552 (p < 0.05) and positive
      likelihood ratio of 2.2. CONCLUSION: Chest radiography is a safe and useful as a
      diagnostic tool of LVH in CKD patients on HD.

PMID- 25055358
TI  - Cross-cultural adaptation to Portuguese of tools for assessing the nutritional
      status of patients on dialysis.
AB  - INTRODUCTION: The 7 point subjective global assessment (7p-SGA) and the
      malnutrition inflammation score (MIS) are tools commonly applied for the
      assessment of nutritional status in dialyzed patients. Both were developed in
      English and require translation to Portuguese to be applied in Brazil. The cross
      cultural equivalence process ensures semantic and measurement equivalence of a
      translated tool. OBJECTIVE: To perform the cross-cultural adaptation to
      Portuguese of the 7p-SGA and MIS. METHODS: Semantic equivalence was performed by
      the back-translation method and by assessing the degree of similarity between the
      original instrument and that back-translated from Portuguese to English (Back
      translation). The assessment of the equivalence measurement was made by
      evaluating the intern reliability (Cronbach's alpha) and interobserver
      reliability (two observers). One-hundred and one elderly patients on hemodialysis
      (HD) were included. RESULTS: Both instruments showed a high degree of semantic
      similarity with results close to the maximum value (7p-SGA 96.8 +/- 7.8 and MIS
      99.6 +/- 1.4). The intern consistency showed a Cronbach's alpha value for 7p-SGA
      of 0.72 and of 0.53 for MIS. The interobserver reproducibility of 7p-SGA was
      moderate (intraclass coefficient [ICC] = 0.74 [95% CI: 0.58; 0.84]), while for
      MIS was strong (ICC = 0.88 [95% CI: 0.81; 0.93]). CONCLUSION: The 7p-SGA and MIS
      translated into Portuguese can be applied for assessing the nutritional status of
      elderly patients on HD. Studies testing the applicability of these instruments in
      adult patients on HD and in peritoneal dialysis should yet be performed.

PMID- 25055359
TI  - Histopathological analysis of pre-implantation donor kidney biopsies: association
      with graft survival and function in one year post-transplantation.
AB  - INTRODUCTION: Pre-implantation kidney biopsy is a decision-making tool when
      considering the use of grafts from deceased donors with expanded criteria,
      implanting one or two kidneys and comparing this to post-transplantation
      biopsies. The role of histopathological alterations in kidney compartments as a
      prognostic factor in graft survival and function has had conflicting results.
      OBJECTIVE: This study evaluated the prevalence of chronic alterations in pre
      implant biopsies of kidney grafts and the association of findings with graft
      function and survival in one year post-transplant. METHODS: 110 biopsies were
      analyzed between 2006 and 2009 at Santa Casa de Porto Alegre, including live
      donors, ideal deceased donors and those with expanded criteria. The score was
      computed according to criteria suggested by Remuzzi. The glomerular filtration
      rate (GFR) was calculated using the abbreviated MDRD formula. RESULTS: No
      statistical difference was found in the survival of donors stratified according
      to Remuzzi criteria. The GFR was significantly associated with the total scores
      in the groups with mild and moderate alterations, and in the kidney compartments
      alone, by univariate analysis. The multivariate model found an association with
      the presence of arteriosclerosis, glomerulosclerosis, acute rejection and delayed
      graft function. CONCLUSION: Pre-transplant chronic kidney alterations did not
      influence the post-transplantation one-year graft survival, but arteriosclerosis
      and glomerulosclerosis is predictive of a worse GFR. Delayed graft function and
      acute rejection are independent prognostic factors.

PMID- 25055360
TI  - The 600 kidney transplants performed at the Botucatu Medical School Hospital -
      UNESP: changes over.
AB  - INTRODUCTION: A progressive improvement in kidney transplant outcomes has been
      achieved over the last decades. OBJECTIVE: To determine the degree to which this
      has occurred in our center, we conducted an outcome analysis of our kidney
      transplant program during three different time periods, especially focusing on
      patient and graft survival. METHODS: The 600 kidney transplants performed at
      Botucatu Medical School/UNESP up to December 2011 were examined. Three different
      time periods were chosen to correspond with major shifts in immunosuppressant
      usage: Era 1 (1987-2000), cyclosporine and azathioprine usage (n = 180); Era 2
      (2001-2006), cyclosporine and mycophenolate mofetil usage (n = 120); and Era 3
      (2007-2011), tacrolimus and mycophenolate (n = 300). RESULTS: Compared with the
      first era, mean recipient age, diabetes prevalence, and the number of living
      donor transplantations (60%) were increased in the third era. Induction therapy
      was used in 75% of the cases in Era 3, 46.6% in Era 2, and in 3.9% in Era 1 (p <
      0.0001). The mean number of transplants/year rose from 14 in Era 1 to 75 in Era
      3. Overall survival according to donor type was similar to that reported in the
      literature. Five-year graft survival following deceased donor transplantation
      progressively increased from 13.1% (Era 1) to 81.9% (Era 3). CONCLUSION:
      Significant differences were observed over time. The percentage of living donors
      decreased as that of deceased donors increased. Survival after deceased donor
      transplants was greatest in Era 3, probably due to the improved experience of the
      medical team, and to the use of tacrolimus and mycophenolate mofetil combination
      with induction.

PMID- 25055361
TI  - Mineral and bone disorder and vascular calcification in patients with chronic
      kidney disease.
AB  - Vascular calcifications has been associated with bone and mineral disorders. The
      alterations in the serum level of calcium concentrations and phosphate are
      importants factors implicated in the arterial calcification in chronic kidney
      disease. The pathogenesis of vascular calcification is a complex mechanism and
      not completely clear, being able to correspond to an active process of cellular
      transformation and heterotopic ossification. Beyond the hypercalcemia and
      hyperphosphatemia, they are involved in this process changes in the metabolism of
      inhibitors and promoters of calcification such as fetuin A, osteopontin,
      osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified
      arterial injury are available several complementary methods, a method of estimate
      of the cardiovascular risk based on plain radiographs of the lumbar column and
      another method based on simple x-rays of the pelvis and hands. Below, we will
      present a review approching the link between vascular calcifications and mineral
      disorders. 

PMID- 25055362
TI  - Hemolytic-Uremic Syndrome in childhood.
AB  - There is a group of diseases that may manifest with thrombotic microangiopathy
      and present clinical overlap. Among these we emphasize the thrombotic
      thrombocytopenic purpura and Hemolytic Uremic Syndrome, and the latter can occur
      by the action of toxins, systemic diseases, overactivation of the alternative
      complement system pathway, which can occur due to changes in regulatory proteins
      (atypical HUS) and finally, idiopathic. You must carry out a series of tests to
      differentiate them. aHUS is a diagnosis of exclusion of other causes of MAT. The
      treatment of aHUS with plasma therapy, results in most cases with good shortterm
      response, especially hematological; however, it is a progressive and devastating
      disease and can lead to death and terminal chronic renal disease. Treatment with
      plasma displays great recurrence of long-term disease and renal insufficiency.
      Eculizumab, a monoclonal antibody anti-C5, has been associated with hematological
      remission, benefits on renal function and no need of plasma therapy.

PMID- 25055363
TI  - The quest for a better understanding of chronic kidney disease complications: an
      update on uremic toxins.
AB  - Chronic kidney disease is characterized by a progressive reduction of glomerular
      filtration rate and/or the appearance of proteinuria, and subsequently the
      progressive retention of organic waste compounds called uremic toxins (UT). Over
      the last decades, a large number of such compounds have been identified and their
      effects on organs and tissues, especially the cardiovascular system, has been
      demonstrated. In this review, we present the current classification of UT, as
      proposed by the EUTox Group, and the effects of some of the probably most
      important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para
      cresyl sulfate. We provide an overview on therapeutic approaches aimed to
      increase their extracorporeal removal via convective and/or adsorptive strategies
      and to lower their intestinal production/ absorption via dietetic and
      pharmacological interventions. The recognition that multiple toxins contribute to
      the uremia supports the need for new therapeutic targets, with a potentially
      positive impact on CKD progression and survival.

PMID- 25055364
TI  - Applicability of subjective global assessment and malnutrition inflammation score
      in the assessment of nutritional status on chronic kidney disease.
AB  - Up to now, there is no single method that provides complete and unambiguous
      assessment of the nutritional status in chronic kidney disease (CKD). Therefore,
      it has been recommended the use of many nutritional markers. The subjective
      global assessment (SGA) contains questions regarding the clinical history and
      physical examination. Subsequently, other versions of the SGA were developed. The
      malnutrition inflammation score (MIS) was also developed from the original
      version of the SGA and consists of 70% of the items common to SGA in addition to
      objective questions. Since many modifications were proposed in the original form
      of SGA, the use of these questionnaires in CKD patients has increased
      substantially in clinical practice. Therefore, this paper aims to review the
      applicability of the SGA and MIS when applied to assess the nutritional status of
      CKD patients.

PMID- 25055365
TI  - Cognitive alterations in chronic kidney disease: an update.
AB  - Impairment of cognitive functions occurs frequently in chronic kidney disease
      (CKD). The conditions most associated with this decline are depression, delirium,
      mild cognitive impairment and dementia. The mechanisms involved have not been
      established yet, but some factors, as neuronal damage by uremic toxins,
      cerebrovascular ischemic lesions, oxidative stress, chronic inflammation, anemia,
      hyperhomocysteinemia, the endothelial dysfunction may play a critical role. The
      neuropsychological performance improves with the initiation of dialysis, although
      some cognitive dysfunctions remain even after treatment, especially in the areas
      of attention, cognitive flexibility, memory and learning. Kidney transplantation
      may improve and even reverse some cognitive deficits detected in the dialysis
      period, despite some compromise in verbal memory and executive functions remain
      after transplantation. The diagnosis of cognitive decline in patients with CKD
      may have an important impact on the management and prognosis. This paper presents
      an update on the decline of cognitive function in patients with CKD.

PMID- 25055366
TI  - [Star fruit as a cause of acute kidney injury].
AB  - The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It
      is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent
      studies show that the toxicity of the fruit differs between the patients and may
      be explained by single biological responses, age, and the intake quantity of the
      neurotoxin in each fruit in addition to glomerular filtration rate given by each
      patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent
      and may lead to the deposition of crystals of calcium oxalate intratubular, as
      well as by direct injury to the renal tubular epithelium, leading to apoptosis of
      the same. We report the case of a patient who after ingestion of the juice and
      fresh fruit, developed acute renal failure requiring dialysis, evolving with
      favourable outcome and recovery of renal function. 

PMID- 25055367
TI  - Report of four cases of Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome is rare. Although its diagnosis depends on cardinal
      clinical manifestations which appear in childhood, we report four cases of Bardet
      Biedl syndrome lately diagnosed in a dialysis center. Three cases were diagnosed
      in end-stage renal disease patients when they started maintenance hemodialysis,
      and one case was diagnosed through screening among hemodialysis patients'
      relatives. Although pediatricians have more opportunity to diagnose the syndrome,
      nephrologists are important during the treatment, since renal failure is the main
      cause of death among Bardet-Biedl syndrome patients. Moreover, late diagnosis of
      the syndrome among patients with end-stage renal disease can help to detect new
      cases through the screening among hemodialysis patients' relatives. 

PMID- 25055368
TI  - A cloud-based approach for interoperable electronic health records (EHRs).
AB  - We present a cloud-based approach for the design of interoperable electronic
      health record (EHR) systems. Cloud computing environments provide several
      benefits to all the stakeholders in the healthcare ecosystem (patients,
      providers, payers, etc.). Lack of data interoperability standards and solutions
      has been a major obstacle in the exchange of healthcare data between different
      stakeholders. We propose an EHR system - cloud health information systems
      technology architecture (CHISTAR) that achieves semantic interoperability through
      the use of a generic design methodology which uses a reference model that defines
      a general purpose set of data structures and an archetype model that defines the
      clinical data attributes. CHISTAR application components are designed using the
      cloud component model approach that comprises of loosely coupled components that
      communicate asynchronously. In this paper, we describe the high-level design of
      CHISTAR and the approaches for semantic interoperability, data integration, and
      security. 

PMID- 25055369
TI  - Source selection for real-time user intent recognition toward volitional control
      of artificial legs.
AB  - Various types of data sources have been used to recognize user intent for
      volitional control of powered artificial legs. However, there is still a debate
      on what exact data sources are necessary for accurately and responsively
      recognizing the user's intended tasks. Motivated by this widely interested
      question, in this study we aimed to 1) investigate the usefulness of different
      data sources commonly suggested for user intent recognition and 2) determine an
      informative set of data sources for volitional control of prosthetic legs. The
      studied data sources included eight surface electromyography (EMG) signals from
      the residual thigh muscles of transfemoral (TF) amputees, ground reaction
      forces/moments from a prosthetic pylon, and kinematic measurements from the
      residual thigh and prosthetic knee. We then ranked and included data sources
      based on the usefulness for user intent recognition and selected a reduced number
      of data sources that ensured accurate recognition of the user's intended task by
      using three source selection algorithms. The results showed that EMG signals and
      ground reaction forces/moments were more informative than prosthesis kinematics.
      Nine to eleven of all the initial data sources were sufficient to maintain 95%
      accuracy for recognizing the studied seven tasks without missing additional task
      transitions in real time. The selected data sources produced consistent system
      performance across two experimental days for four recruited TF amputee subjects,
      indicating the potential robustness of the selected data sources. Finally, based
      on the study results, we suggested a protocol for determining the informative
      data sources and sensor configurations for future development of volitional
      control of powered artificial legs. 

PMID- 25055370
TI  - A learning scheme for reach to grasp movements: on EMG-based interfaces using
      task specific motion decoding models.
AB  - A learning scheme based on random forests is used to discriminate between
      different reach to grasp movements in 3-D space, based on the myoelectric
      activity of human muscles of the upper-arm and the forearm. Task specificity for
      motion decoding is introduced in two different levels: Subspace to move toward
      and object to be grasped. The discrimination between the different reach to grasp
      strategies is accomplished with machine learning techniques for classification.
      The classification decision is then used in order to trigger an EMG-based task
      specific motion decoding model. Task specific models manage to outperform
      "general" models providing better estimation accuracy. Thus, the proposed scheme
      takes advantage of a framework incorporating both a classifier and a regressor
      that cooperate advantageously in order to split the task space. The proposed
      learning scheme can be easily used to a series of EMG-based interfaces that must
      operate in real time, providing data-driven capabilities for multiclass problems,
      that occur in everyday life complex environments. 

PMID- 25055371
TI  - Rotated Hough filtering for automatically distinguishing the collagen bundles in
      the most superficial layer of articular cartilage.
AB  - The structure of the collagen matrix in the most superficial layer of articular
      cartilage (AC) is particularly critical to the wear and tensile resistance of AC.
      Disruption of the collagen network leads to rapid wear of the articular surface,
      which is a major contributory factor of osteoarthritis. Interwoven fiber bundles
      have been observed in the most superficial layer of healthy AC under confocal
      microscopy, but gradually disappear with age and pathological change of AC. The
      image analysis techniques developed in this paper aimed to provide a quantitative
      description of the relationship between the presence of the fiber bundles in the
      lamina splendens and health status of AC. The result of this quantitative study
      confirmed the existence of fiber bundles in healthy AC, and the accuracy of the
      identified fiber bundles was up to 90%. With the development of confocal
      arthroscopy for imaging microstructure of AC without biopsy, the image analysis
      technique can aid to efficiently assess the physiological status of AC for
      orthopedic clinics. 

PMID- 25055372
TI  - Correlation modeling for compression of computed tomography images.
AB  - Computed tomography (CT) is a noninvasive medical test obtained via a series of X
      ray exposures resulting in 3-D images that aid medical diagnosis. Previous
      approaches for coding such 3-D images propose to employ multicomponent transforms
      to exploit correlation among CT slices, but these approaches do not always
      improve coding performance with respect to a simpler slice-by-slice coding
      approach. In this paper, we propose a novel analysis which accurately predicts
      when the use of a multicomponent transform is profitable. This analysis models
      the correlation coefficient r based on image acquisition parameters readily
      available at acquisition time. Extensive experimental results from multiple image
      sensors suggest that multicomponent transforms are appropriate for images with
      correlation coefficient r in excess of 0.87. 

PMID- 25055373
TI  - Segmentation of the thoracic aorta in noncontrast cardiac CT images.
AB  - Studies have shown that aortic calcification is associated with cardiovascular
      disease. In this study, a method for localization, centerline extraction, and
      segmentation of the thoracic aorta in noncontrast cardiac-computed tomography
      (CT) images, toward the detection of aortic calcification, is presented. The
      localization of the right coronary artery ostium slice is formulated as a
      regression problem whose input variables are obtained from simple intensity
      features computed from a pyramid representation of the slice. The localization,
      centerline extraction, and segmentation of the aorta are formulated as optimal
      path detection problems. Dynamic programming is applied in the Hough space for
      localizing key center points in the aorta which guide the centerline tracing
      using a fast marching-based minimal path extraction framework. The input volume
      is then resampled into a stack of 2-D cross-sectional planes orthogonal to the
      obtained centerline. Dynamic programming is again applied for the segmentation of
      the aorta in each slice of the resampled volume. The obtained segmentation is
      finally mapped back to its original volume space. The performance of the proposed
      method was assessed on cardiac noncontrast CT scans and promising results were
      obtained. 

PMID- 25055374
TI  - Lesion area detection using source image correlation coefficient for CT perfusion
      imaging.
AB  - Computer tomography (CT) perfusion imaging is widely used to calculate brain
      hemodynamic quantities such as cerebral blood flow, cerebral blood volume, and
      mean transit time that aid the diagnosis of acute stroke. Since perfusion source
      images contain more information than hemodynamic maps, good utilization of the
      source images can lead to better understanding than the hemodynamic maps alone.
      Correlation-coefficient tests are used in our approach to measure the similarity
      between healthy tissue time-concentration curves and unknown curves. This
      information is then used to differentiate penumbra and dead tissues from healthy
      tissues. The goal of the segmentation is to fully utilize information in the
      perfusion source images. Our method directly identifies suspected abnormal areas
      from perfusion source images and then delivers a suggested segmentation of
      healthy, penumbra, and dead tissue. This approach is designed to handle CT
      perfusion images, but it can also be used to detect lesion areas in magnetic
      resonance perfusion images. 

PMID- 25055375
TI  - Quantitative assessment of fetal well-being through CTG recordings: a new
      parameter based on phase-rectified signal average.
AB  - Since the 1980s, cardiotocography (CTG) has been the most diffused technique to
      monitor fetal well-being during pregnancy. CTG consists of the simultaneous
      recording of fetal heart rate (FHR) signal and uterine contractions and its
      interpretation is usually performed through visual inspection by trained
      obstetric personnel. To reduce inter- and intraobserver variabilities and to
      improve the efficacy of prenatal diagnosis, new quantitative parameters,
      extracted from the CTG digitized signals, have been proposed as additional tools
      in the clinical diagnosis process. In this paper, a new parameter computed on FHR
      time series and based on the phase-rectified signal average curve (PRSA) is
      introduced. It is defined as acceleration phase-rectified slope (APRS) or
      deceleration phase-rectified slope (DPRS) depending on the slope sign of the PRSA
      curve. The new PRSA parameter was applied to FHR time series of 61 healthy and 61
      intrauterine growth restricted (IUGR) fetuses during CTG nonstress tests.
      Performance of APRS and DPRS was compared with 1) the results provided by other
      parameters extracted from the PRSA curve itself but already existing in the
      literature, and 2) other clinical indices provided by computerized
      cardiotocographic systems. APRS and DPRS indices performed better than any other
      parameter in this study in the distinction between healthy and IUGR fetuses. Our
      results suggest this new index might reliably contribute to the quality of early
      fetal diagnosis. 

PMID- 25055376
TI  - Evolution-based hierarchical feature fusion for ultrasonic liver tissue
      characterization.
AB  - This paper presents an evolution-based hierarchical feature fusion system that
      selects the dominant features among multiple feature vectors for ultrasonic liver
      tissue characterization. After extracting the spatial gray-level dependence
      matrices, multiresolution fractal feature vectors and multiresolution energy
      feature vectors, the system utilizes evolution-based algorithms to select
      features. In each feature space, features are selected independently to compile a
      feature subset. As the features of different feature vectors contain
      complementary information, a feature fusion process is used to combine the
      subsets generated from different vectors. Features are then selected from the
      fused feature vector to form a fused feature subset. The selected features are
      used to classify ultrasonic images of liver tissue into three classes: hepatoma,
      cirrhosis, and normal liver. Experiment results show that the classification
      accuracy of the fused feature subset is superior to that derived by using
      individual feature subsets. Moreover, the findings demonstrate that the proposed
      algorithm is capable of selecting discriminative features among multiple feature
      vectors to facilitate the early detection of hepatoma and cirrhosis via
      ultrasonic liver imaging. 

PMID- 25055377
TI  - Optimization of chemical fungicide combinations targeting the maize fungal
      pathogen, Bipolaris maydis: a systematic quantitative approach.
AB  - To control the southern corn leaf blight, a severe disease of maize around the
      world, a combination of fungicides is often more potent than using individual
      fungicides. However, the number of possible combinations increases exponentially
      with the increase of the number of fungicides combined and their concentrations.
      It is thus extremely challenging to identify effective fungicide combinations by
      trial and error from all possible combinations. In this paper, a systematic
      approach based on a support vector machine, a machine learning algorithm, is
      proposed to searching for the optimal combinations using only a limited number of
      measurements. The constructed model also incorporates information related to the
      inhibition rate (IR) and the cost of each composing fungicide into the
      optimization process. With this method, we show that only around 130 measurements
      on a coarse grid of concentrations out of thousands of possible experiments are
      sufficient to reconstruct the response model and to obtain the optimal fungicide
      combinations. Experimental results demonstrate that the optimized combinations
      can achieve an IR greater than 90%, while the required concentrations and the
      cost of individual fungicides are dramatically reduced. We anticipate that this
      method should be equally effective in the search for optimal combinations of
      multiple compounds in other diseases.

PMID- 25055378
TI  - Electromagnetic thermotherapy for deep organ ablation by using a needle array
      under a synchronized-coil system.
AB  - Thermal ablation by using electromagnetic thermotherapy (EMT) has been a
      promising cancer modality in recent years. It has relatively few side effects and
      has therefore been extensively investigated for a variety of medical applications
      in internal medicine and surgery. The EMT system applies a high-frequency
      alternating electromagnetic field to heat up the needles which are inserted into
      the target tumor to cause tumor ablation. In this study, a new synchronized-coil
      EMT system was demonstrated, which was equipped with two synchronized coils and
      magnetic field generators to provide a long-range, penetrated electromagnetic
      field to effectively heat up the needles. The heating effect of the needles at
      the center of the two coils was first explored. The newly designed two-section
      needle array combined with the synchronized-coil EMT system was thus demonstrated
      in the in vitro and in vivo animal experiments. Experimental data showed that the
      developed system is promising for minimally invasive surgery since it might
      provide superior performance for thermotherapy in cancer treatment. 

PMID- 25055379
TI  - Biological channel modeling and implantable UWB antenna design for neural
      recording systems.
AB  - Ultrawideband (UWB) short-range communication systems have proved to be valuable
      in medical technology, particularly for implanted devices, due to their low-power
      consumption, low cost, small size, and high data rates. Neural activity
      monitoring in the brain requires high data rate (800 kb/s per neural sensor), and
      we target a system supporting a large number of sensors, in particular, aggregate
      transmission above 430 Mb/s (~512 sensors). Knowledge of channel behavior is
      required to determine the maximum allowable power to 1) respect ANSI guidelines
      for avoiding tissue damage, and 2) respect FCC guidelines on unlicensed
      transmissions. We utilize a realistic model of the biological channel to inform
      the design of antennas for the implanted transmitter and the external receiver
      under these requirements. Antennas placement is examined under two scenarios
      having contrasting power constraints. Performance of the system within the
      biological tissues is examined via simulation and experiment. Our miniaturized
      antennas, 12 mm *12 mm, need worst-case receiver sensitivities of -38 and -30.5
      dBm for the first and second scenarios, respectively. These sensitivities allow
      us to successfully detect signals transmitted through tissues in the 3.1-10.6-GHz
      UWB band. 

PMID- 25055380
TI  - Diffuse optical tomography enhanced by clustered sparsity for functional brain
      imaging.
AB  - Diffuse optical tomography (DOT) is a noninvasive technique which measures
      hemodynamic changes in the tissue with near infrared light, which has been
      increasingly used to study brain functions. Due to the nature of light
      propagation in the tissue, the reconstruction problem is severely ill-posed. For
      linearized DOT problems, sparsity regularization has achieved promising results
      over conventional Tikhonov regularization in recent experimental research. As
      extensions to standard sparsity, it is widely known that structured sparsity
      based methods are often superior in terms of reconstruction accuracy, when the
      data follows some structures. In this paper, we exploit the structured sparsity
      of diffuse optical images. Based on the functional specialization of the brain,
      it is observed that the in vivo absorption changes caused by a specific brain
      function would be clustered in certain region(s) and not randomly distributed.
      Thus, a new algorithm is proposed for this clustered sparsity reconstruction
      (CSR). Results of numerical simulations and phantom experiments have demonstrated
      the superiority of the proposed method over the state-of-the-art methods. An
      example from human in vivo measurements further confirmed the advantages of the
      proposed CSR method. 

PMID- 25055381
TI  - Attenuation correction synthesis for hybrid PET-MR scanners: application to brain
      studies.
AB  - Attenuation correction is an essential requirement for quantification of positron
      emission tomography (PET) data. In PET/CT acquisition systems, attenuation maps
      are derived from computed tomography (CT) images. However, in hybrid PET/MR
      scanners, magnetic resonance imaging (MRI) images do not directly provide a
      patient-specific attenuation map. The aim of the proposed work is to improve
      attenuation correction for PET/MR scanners by generating synthetic CTs and
      attenuation maps. The synthetic images are generated through a multi-atlas
      information propagation scheme, locally matching the MRI-derived patient's
      morphology to a database of MRI/CT pairs, using a local image similarity measure.
      Results show significant improvements in CT synthesis and PET reconstruction
      accuracy when compared to a segmentation method using an ultrashort-echo-time MRI
      sequence and to a simplified atlas-based method. 

PMID- 25055382
TI  - Reducing multiplexing artifacts in multi-pinhole SPECT with a stacked silicon
      germanium system: a simulation study.
AB  - In pinhole single photon emission computed tomography (SPECT), multi-pinhole
      collimators can increase sensitivity but may lead to projection overlap, or
      multiplexing, which can cause image artifacts. In this work, we explore whether a
      stacked-detector configuration with a germanium and a silicon detector, used with
      123I (27-32, 159 keV), where little multiplexing occurs in the Si projections,
      can reduce image artifacts caused by highly-multiplexed Ge projections.
      Simulations are first used to determine a reconstruction method that combines the
      Si and Ge projections to maximize image quality. Next, simulations of different
      pinhole configurations (varying projection multiplexing) in conjunction with
      digital phantoms are used to examine whether additional Si projections mitigate
      artifacts from the multiplexing in the Ge projections. Reconstructed images using
      both Si and Ge data are compared to those using Ge data alone. Normalized mean
      square error and normalized standard deviation provide a quantitative evaluation
      of reconstructed images' error and noise, respectively, and are used to evaluate
      the impact of the additional nonmultiplexed data on image quality. For a
      qualitative comparison, the differential point response function is used to
      examine multiplexing artifacts. Results show that in cases of highly-multiplexed
      Ge projections, the addition of low-multiplexed Si projections helps to reduce
      image artifacts both quantitatively and qualitatively.

PMID- 25055383
TI  - Real-time segmentation and recognition of surgical tasks in cataract surgery
      videos.
AB  - In ophthalmology, it is now common practice to record every surgical procedure
      and to archive the resulting videos for documentation purposes. In this paper, we
      present a solution to automatically segment and categorize surgical tasks in real
      time during the surgery, using the video recording. The goal would be to
      communicate information to the surgeon in due time, such as recommendations to
      the less experienced surgeons. The proposed solution relies on the content-based
      video retrieval paradigm: it reuses previously archived videos to automatically
      analyze the current surgery, by analogy reasoning. Each video is segmented, in
      real-time, into an alternating sequence of idle phases, during which no
      clinically-relevant motions are visible, and action phases. As soon as an idle
      phase is detected, the previous action phase is categorized and the next action
      phase is predicted. A conditional random field is used for categorization and
      prediction. The proposed system was applied to the automatic segmentation and
      categorization of cataract surgery tasks. A dataset of 186 surgeries, performed
      by ten different surgeons, was manually annotated: ten possibly overlapping
      surgical tasks were delimited in each surgery. Using the content of action phases
      and the duration of idle phases as sources of evidence, an average recognition
      performance of Az = 0.832 +/- 0.070 was achieved.

PMID- 25055384
TI  - Effect of anatomical variability on electric field characteristics of
      electroconvulsive therapy and magnetic seizure therapy: a parametric modeling
      study.
AB  - Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are
      conventionally applied with a fixed stimulus current amplitude, which may result
      in differences in the neural stimulation strength and focality across patients
      due to interindividual anatomical variability. The objective of this study is to
      quantify the effect of head anatomical variability associated with age, sex, and
      individual differences on the induced electric field characteristics in ECT and
      MST. Six stimulation modalities were modeled including bilateral and right
      unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST
      with circular, cap, and double-cone coils. The electric field was computed using
      the finite element method in a parameterized spherical head model representing
      the variability in the general population. Head tissue layer thicknesses and
      conductivities were varied to examine the impact of interindividual anatomical
      differences on the stimulation strength, depth, and focality. Skull conductivity
      most strongly affects the ECT electric field, whereas the MST electric field is
      independent of tissue conductivity variation in this model but is markedly
      affected by differences in head diameter. Focal ECT electrode configurations such
      as FEAST is more sensitive to anatomical variability than that of less focal
      paradigms such as BL ECT. In MST, anatomical variability has stronger influence
      on the electric field of the cap and circular coils compared to the double-cone
      coil, possibly due to the more superficial field of the former. The variability
      of the ECT and MST electric fields due to anatomical differences should be
      considered in the interpretation of existing studies and in efforts to improve
      dosing approaches for better control of stimulation strength and focality across
      patients, such as individualization of the current amplitude. The conventional
      approach to individualizing dosage by titrating the number of pulses cannot
      compensate for differences in the spatial extent of stimulation that result from
      anatomical variability. 

PMID- 25055385
TI  - Computer-Aided Prostate Cancer Diagnosis From Digitized Histopathology: A Review
      on Texture-Based Systems.
AB  - Prostate cancer (PCa) is currently diagnosed by microscopic evaluation of biopsy
      samples. Since tissue assessment heavily relies on the pathologists level of
      expertise and interpretation criteria, it is still a subjective process with high
      intra- and interobserver variabilities. Computer-aided diagnosis (CAD) may have a
      major impact on detection and grading of PCa by reducing the pathologists reading
      time, and increasing the accuracy and reproducibility of diagnosis outcomes.
      However, the complexity of the prostatic tissue and the large volumes of data
      generated by biopsy procedures make the development of CAD systems for PCa a
      challenging task. The problem of automated diagnosis of prostatic carcinoma from
      histopathology has received a lot of attention. As a result, a number of CAD
      systems, have been proposed for quantitative image analysis and classification.
      This review aims at providing a detailed description of selected literature in
      the field of CAD of PCa, emphasizing the role of texture analysis methods in
      tissue description. It includes a review of image analysis tools for image
      preprocessing, feature extraction, classification, and validation techniques used
      in PCa detection and grading, as well as future directions in pursuit of better
      texture-based CAD systems. 

PMID- 25055386
TI  - Optimization of a multilayer neural network by using minimal redundancy maximal
      relevance-partial mutual information clustering with least square regression.
AB  - In this paper, an optimized multilayer feed-forward network (MLFN) is developed
      to construct a soft sensor for controlling naphtha dry point. To overcome the two
      main flaws in the structure and weight of MLFNs, which are trained by a back
      propagation learning algorithm, minimal redundancy maximal relevance-partial
      mutual information clustering (mPMIc) integrated with least square regression
      (LSR) is proposed to optimize the MLFN. The mPMIc can determine the location of
      hidden layer nodes using information in the hidden and output layers, as well as
      remove redundant hidden layer nodes. These selected nodes are highly related to
      output data, but are minimally correlated with other hidden layer nodes. The
      weights between the selected hidden layer nodes and output layer are then updated
      through LSR. When the redundant nodes from the hidden layer are removed, the
      ideal MLFN structure can be obtained according to the test error results. In
      actual applications, the naphtha dry point must be controlled accurately because
      it strongly affects the production yield and the stability of subsequent
      operational processes. The mPMIc-LSR MLFN with a simple network size performs
      better than other improved MLFN variants and existing efficient models. 

PMID- 25055387
TI  - Separating arterial and venous-related components of photoplethysmographic
      signals for accurate extraction of oxygen saturation and respiratory rate.
AB  - We propose an algorithm for separating arterial and venous-related signals using
      second-order statistics of red and infrared signals in a blind source separation
      technique. The separated arterial signal is used to compute accurate arterial
      oxygen saturation. We have also introduced an algorithm for extracting the
      respiratory pattern from the extracted venous-related signal. In addition to real
      time monitoring, respiratory rate is also extracted. Our experimental results
      from multiple subjects show that the proposed separation technique is extremely
      useful for extracting accurate arterial oxygen saturation and respiratory rate.
      Specifically, the breathing rate is extracted with average root mean square
      deviation of 1.89 and average mean difference of -0.69. 

PMID- 25055388
TI  - Dependence Independence Measure for Posterior and Anterior EMG Sensors Used in
      Simple and Complex Finger Flexion Movements: Evaluation Using SDICA.
AB  - Identification of simple and complex finger flexion movements using surface
      electromyography (sEMG) and a muscle activation strategy is necessary to control
      human-computer interfaces such as prosthesis and orthoses. In order to identify
      these movements, sEMG sensors are placed on both anterior and posterior muscle
      compartments of the forearm. In general, the accuracy of myoelectric
      classification depends on several factors, which include number of sensors,
      features extraction methods, and classification algorithms. Myoelectric
      classification using a minimum number of sensors and optimal electrode
      configuration is always a challenging task. Sometimes, using several sensors
      including high density electrodes will not guarantee high classification
      accuracy. In this research, we investigated the dependence and independence
      nature of anterior and posterior muscles during simple and complex finger flexion
      movements. The outcome of this research shows that posterior parts of the hand
      muscles are dependent and hence responsible for most of simple finger flexion. On
      the other hand, this study shows that anterior muscles are responsible for most
      complex finger flexion. This also indicates that simple finger flexion can be
      identified using sEMG sensors connected only on anterior muscles (making
      posterior placement either independent or redundant), and vice versa is true for
      complex actions which can be easily identified using sEMG sensors on posterior
      muscles. The result of this study is beneficial for optimal electrode
      configuration and design of prosthetics and other related devices using a minimum
      number of sensors. 

PMID- 25055389
TI  - Evolutionary path control strategy for solving many-objective optimization
      problem.
AB  - The number of objectives in many-objective optimization problems (MaOPs) is
      typically high and evolutionary algorithms face severe difficulties in solving
      such problems. In this paper, we propose a new scalable evolutionary algorithm,
      called evolutionary path control strategy (EPCS), for solving MaOPs. The central
      component of our algorithm is the use of a reference vector that helps
      simultaneously minimizing all the objectives of an MaOP. In doing so, EPCS
      employs a new fitness assignment strategy for survival selection. This strategy
      consists of two procedures and our algorithm applies them sequentially. It
      encourages a population of solutions to follow a certain path reaching toward the
      Pareto optimal front. The essence of our strategy is that it reduces the number
      of nondominated solutions to increase selection pressure in evolution.
      Furthermore, unlike previous work, EPCS is able to apply the classical Pareto
      dominance relation with the new fitness assignment strategy. Our algorithm has
      been tested extensively on several scalable test problems, namely five DTLZ
      problems with 5 to 40 objectives and six WFG problems with 2 to 13 objectives.
      Furthermore, the algorithm has been tested on six CEC09 problems having 2 or 3
      objectives. The experimental results show that EPCS is capable of finding better
      solutions compared to other existing algorithms for problems with an increasing
      number of objectives. 

PMID- 25055390
TI  - Adaptive ranking mutation operator based differential evolution for constrained
      optimization.
AB  - Differential evolution (DE) is a powerful evolutionary algorithm (EA) for
      numerical optimization. Combining with the constraint-handling techniques,
      recently, DE has been successfully used for the constrained optimization problems
      (COPs). In this paper, we propose the adaptive ranking mutation operator (ARMOR)
      for DE when solving the COPs. The ARMOR is expected to make DE converge faster
      and achieve feasible solutions faster. In ARMOR, the solutions are adaptively
      ranked according to the situation of the current population. More specifically,
      the population is classified into three situations, i.e., infeasible situation,
      semi-feasible situation, and feasible situation. In the infeasible situation, the
      solutions are ranked only based on their constraint violations; in the semi
      feasible situation, they are ranked according to the transformed fitness; while
      in the feasible situation, the objective function value is used to assign ranks
      to different solutions. In addition, the selection probability of each solution
      is calculated differently in different situations. The ARMOR is simple, and it
      can be easily combined with most of constrained DE (CDE) variants. As
      illustrations, we integrate our approach into three representative CDE variants
      to evaluate its performance. The 24 benchmark functions presented in CEC 2006 and
      18 benchmark functions presented in CEC 2010 are chosen as the test suite.
      Experimental results verify our expectation that the ARMOR is able to accelerate
      the original CDE variants in the majority of test cases. Additionally, ARMOR
      based CDE is able to provide highly competitive results compared with other state
      of-the-art EAs. 

PMID- 25055391
TI  - Extension of expiration date for temporary pilot program setting the time and
      place for a hearing before an administrative law judge. Final rule.
AB  - We are extending for one year our pilot program that authorizes the agency to set
      the time and place for a hearing before an administrative law judge (ALJ).
      Extending the pilot program continues our commitment to improve the efficiency of
      our hearing process and provide accurate, high-quality decisions for claimants.
      The current pilot program will expire on August 9, 2014. In this final rule, we
      are extending the expiration date to August 10, 2015. We are making no other
      substantive changes.

PMID- 25055392
TI  - Is summer heat putting you at risk? Dehydration, heart disease, and medications
      may lead to heat exhaustion and falls.

PMID- 25055393
TI  - Final priority; Rehabilitation Training: Rehabilitation Long-Term Training
      program--rehabilitation specialty areas. Final priority.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a priority under the Rehabilitation Training: Rehabilitation Long-Term
      Training program. The Assistant Secretary may use this priority for competitions
      in fiscal year (FY) 2014 and later years in order to fund any of the
      rehabilitation specialty areas listed in this notice. The specific rehabilitation
      specialty areas to be funded in a given year will be listed in a notice inviting
      applications. This priority is designed to ensure that the Department funds high
      quality rehabilitation programs in the following nine rehabilitation specialty
      areas of national need: Rehabilitation Administration (84.129C); Rehabilitation
      Technology (84.129E); Vocational Evaluation and Work Adjustment (84.129F);
      Rehabilitation of Individuals Who Are Mentally Ill (84.129H); Rehabilitation
      Psychology (84.129J); Rehabilitation of Individuals Who are Blind or Have Vision
      Impairments (84.129P); Rehabilitation of Individuals Who are Deaf or Hard of
      Hearing (84.129Q); Job Development and Job Placement Services (84.129R); and
      Comprehensive System of Personnel Development (84.129W). These programs must meet
      rigorous standards in order to provide rehabilitation professionals the training
      and qualifications necessary to meet the current challenges facing State
      vocational rehabilitation (VR) agencies and related agencies and assist
      individuals with disabilities in achieving high-quality employment outcomes.

PMID- 25055394
TI  - Tobacco cessation in India: a priority health intervention.

PMID- 25055395
TI  - New HPV16 viral biomarkers to understand the progression  of cervical lesions
      towards cancer.

PMID- 25055396
TI  - Authors' response.

PMID- 25055397
TI  - Compliance deadline for new HIPAA rules.

PMID- 25055398
TI  - Health care reform: frequently asked questions.

PMID- 25055399
TI  - Dental treatment of the pregnant patient: literature review and guidelines for
      the practicing clinician.
AB  - The purpose of this review article is to assist the practicing clinician by
      categorizing and packaging useful clinical information into a format that will
      assist with the treatment of pregnant patients. Our goal is to offer the
      scientific foundations that lead to current practice guidelines, specifically
      those that are of particular relevance to today's dental professional.

PMID- 25055400
TI  - 8.5 tips for Dental Safety Checklists.

PMID- 25055401
TI  - Diagnostic discussion. Pemphigus vulgaris (PV).

PMID- 25055402
TI  - Management of the anxious dental patient.

PMID- 25055403
TI  - Five factors to dramatically improve the patient experience.

PMID- 25055404
TI  - Your team's personal appearance: why you need a formal, documented office policy
      regarding the way your team looks.

PMID- 25055405
TI  - Weighing up the risks and benefits of androgen deprivation therapy.

PMID- 25055406
TI  - Improving the detection and treatment of schizophrenia.
AB  - Schizophrenia is a debilitating, often chronic, psychotic disorder with early
      onset and a lifetime prevalence of 7.2/1,000. The longer the period without
      treatment, the worse the outcome. In the UK, the mean duration of untreated
      psychosis is one to two years. The new NICE guidelines for schizophrenia
      recommend that all patients who are distressed and have a decline in social
      functioning accompanied by psychotic symptoms or behaviour suggesting psychosis
      should be comprehensively assessed by a specialist mental health service.
      Antipsychotic medication remains the cornerstone of treatment in schizophrenia
      for the acute and the stabilisation-maintenance phase. The NICE guidelines
      recommend the use of psychological, social, occupational and educational
      interventions early in treatment. Mortality rates in schizophrenia are high and
      the majority of premature deaths are accounted for by physical illnesses. These
      include cardiovascular disease, diabetes mellitus, COPD, certain cancers and
      infectious diseases e.g. HIV, hepatitis C, and tuberculosis. Primary care has a
      significant role to play in monitoring mental state and physical health.
      Monitoring mental state is crucial. When relapse is threatened because of poor
      response to treatment, non-adherence to medication, intolerable side effects from
      medication, comorbid substance misuse, or if risk to self or others is suspected,
      GPs should refer the patient to the mental health team. GPs should provide a
      comprehensive health check yearly or more often if there is an indication.

PMID- 25055407
TI  - Diagnosis and management of miscarriage.
AB  - Miscarriage is defined as a pregnancy failure occurring before the completion of
      24 weeks of gestation. Around 10 to 15% of all pregnancies end in early
      spontaneous first trimester miscarriage. Advancing maternal and paternal age are
      known to be associated with increasing chance of miscarriage. Other risk factors
      include being underweight or overweight, smoking and high alcohol consumption.
      Traditional practice classified miscarriage according to the history and findings
      on speculum examination but transvaginal ultrasound scan should now be considered
      the standard test to assess viability of the pregnancy. Assessment of the amount
      of vaginal bleeding experienced is best made in the context of time taken to
      saturate a sanitary pad. Changing a pad soaked with blood and clots more than
      once an hour is an indication of heavy bleeding that requires immediate referral.
      Following confirmation of a viable intrauterine pregnancy, symptoms may resolve.
      If the symptoms worsen, or persist beyond 14 days, a repeat referral should be
      made to the early pregnancy unit for further assessment. If a pregnancy is 12
      weeks' gestation and the woman is rhesus negative, she will require anti-D
      prophylaxis if there are symptoms of bleeding. Expectant management is the first
      line approach, and is encouraged for 7-14 days after diagnosis of miscarriage.
      Most women will miscarry spontaneously during this time and will need no further
      treatment. It is not appropriate if there are risk factors for haemorrhage, or if
      the woman is at increased risk from the effects of haemorrhage. Medical
      management of miscarriage can be offered using misoprostol. Surgical management
      may be chosen by a woman if she has had a previous adverse or traumatic
      experience associated with pregnancy.

PMID- 25055408
TI  - Pigmented lesions.

PMID- 25055409
TI  - X-rays for severe menstrual pain and excessive bleeding. 1914.

PMID- 25055410
TI  - Education is not the filling of a pail but the lighting of a fire.

PMID- 25055412
TI  - CMS responds to stage 2 worries with extra year to meet criteria.

PMID- 25055411
TI  - The hidden cliffs in Obamacare.

PMID- 25055413
TI  - Excessive drug costs could invite price caps: AHIP's Ignagni.

PMID- 25055414
TI  - Complex problems haunt VA.

PMID- 25055415
TI  - Working out wellness.

PMID- 25055416
TI  - Connecting food to healing. Hospitals shift to serving meat raised without
      antibiotics.

PMID- 25055417
TI  - Beyond the theatrics of the VA scandal.

PMID- 25055418
TI  - Don't squander progress on access to care.

PMID- 25055419
TI  - Tracking bug's spread galvanizes staff.

PMID- 25055420
TI  - Promoting research to improve care in the real world.

PMID- 25055421
TI  - [This edition of the journal is dedicated exclusively to hospital archives].

PMID- 25055422
TI  - [Foreword].

PMID- 25055423
TI  - [Evolution of methods for hospital archives management and conservation].

PMID- 25055424
TI  - [Medical and hospital archives, a legacy to value. Practice of the archiving unit
      of Paris' Assistance Public-hospitals].

PMID- 25055425
TI  - [Archives in hospitals and medical domains in France: a network in construction
      ].

PMID- 25055426
TI  - [Municipal archives... those of Chalon-sur-Saone's Hospital. Path of these
      documents issued from public health services and became exceptional municipal
      archives with time].

PMID- 25055428
TI  - [Hospital Archives's future: recommendations of ANAP].

PMID- 25055427
TI  - [Collecting hospital staff's memory. The example of Civil Hospices of Beaune].

PMID- 25055429
TI  - [Hospital archives: state of the art].

PMID- 25055430
TI  - [Origin of the concept of hospital public service].

PMID- 25055431
TI  - [Politics of Civil Hospices of Lyon's legacy development, from two recent
      examples ].

PMID- 25055432
TI  - Developing a blueprint for quality.

PMID- 25055433
TI  - Implementing system updates for CROWNWeb.

PMID- 25055434
TI  - Community-based hospital systems. Managing the costs of a dialysis program in the
      affordable health care system.

PMID- 25055435
TI  - Recipe for a successful PD program needs the right ingredients.

PMID- 25055436
TI  - Urgent-start PD: moving the therapy forward.
AB  - With a continual effort to reduce the number of incident patients starting with a
      central venous catheter, and renewed interest in encouraging home therarpy,
      urgent-start peritoneal dialysis can make a difference.

PMID- 25055437
TI  - Symptom targeted intervention webinar trainings: feedback from participants.
AB  - Professional trainings through the use of webinar format are widely used, but
      participant feedback is seldom studied. In the spring of 2013, 83 nephrology
      social workers participated in weekly webinar trainings to learn how to implement
      Symptom Targeted Intervention (STI) into their clinical practice. At the end of
      the project, participants were asked to complete an online questionnaire to
      provide feedback on the perceived value and effectiveness of the trainings. Sixty
      eight participants completed the questionnaire. The results indicate that social
      workers found the webinar trainings to be very useful and wanted the trainings to
      continue beyond the project. Based on participant feedback, clinical training and
      case presentation through the use of ongoing webinars is a useful education
      modality for nephrology professionals, but more research is indicated to evaluate
      how best to utilize webinars to maximize learning.

PMID- 25055438
TI  - [Violence against disabled persons].

PMID- 25055439
TI  - [Nursing care in an international exchange].

PMID- 25055440
TI  - [Fears are selling well or: do we need more reliability in brain death
      diagnosis?].

PMID- 25055441
TI  - [Violence as a nursing phenomenon].

PMID- 25055442
TI  - [Increased monitoring and documentation requirements in apparently healthy
      newborn infants with prenatal risk anamnesis].

PMID- 25055443
TI  - [Werner Schell honored with the Federal Cross of Merit].

PMID- 25055445
TI  - [Inquiry].

PMID- 25055446
TI  - [3 rules for better allergy protection - experts provide nutrition
      recommendations for mother and baby].

PMID- 25055447
TI  - ["Please no breast feeding religion"].

PMID- 25055448
TI  - ["Please no breast feeding religion"].

PMID- 25055449
TI  - [The required scope of nursing documentation from the legal liability
      perspective].

PMID- 25055450
TI  - [Understanding pain - animated film for children with chronic pain celebrates its
      world premiere].

PMID- 25055451
TI  - [Osteoporosis: risk factors and prevention].
AB  - Osteoporosis is a chronic disease with an increasing prevalence due to the ageing
      of the population. The consequences of this disease are not negligible because of
      the morbidity and mortality associated with it. Osteoporotic fractures are often
      the cause of loss of independence in the elderly, requiring considerable
      resources in terms of health services. Osteoporosis can be prevented effectively,
      but remains underestimated. Thanks to his frequent contacts with the public, the
      pharmacist can play an important role by informing about the disease and raising
      awareness for the prevention of it.

PMID- 25055452
TI  - [Osteoporosis: treatment and pharmaceutical care].
AB  - Osteoporosis is a chronic disease with an increasing prevalence due to the ageing
      of the population. The consequences of this disease are not negligible because of
      the morbidity and mortality associated with it. Osteoporotic fractures are often
      the cause of loss of independence in the elderly, requiring considerable
      resources in terms of health services. Osteoporosis can be prevented and treated.
      However, it remains underestimated, underdiagnosed and undertreated. Thanks to
      his frequent contact with the public, the pharmacist can play an important role
      at multiple levels: supporting patients in treatment, by providing information on
      the disease, its treatment, proper use of medication, adherence and persistence,
      as well as raising awareness for the prevention of osteoporosis and identifying
      patients at risk.

PMID- 25055453
TI  - [Improving the quality of compounded medicines through self-assessment: proof of
      concept].
AB  - A systematic quality control of compounded medicines, and an associated guidance
      of community pharmacists, was identified as a complementary opportunity to
      improve and guarantee the quality of compounded medicines. Before implementing
      this on a national scale, a pilot project was organized. Fifty pharmacies
      prepared the same formula and had it checked regarding labelling, preparation
      reports and analytical parameters. This proof of concept demonstrated that the
      organisation of quality control of compounded medicines by the professional body
      itself is feasible. Such audits fit well in de quality assurance systems in place
      in community pharmacy, where any corrective measures are properly documented and
      implemented. This form of self-regulation has a preventive character for
      detecting defects and contributes to improving the quality of the preparations
      and thus to the patient safety.

PMID- 25055454
TI  - [Major drug related problems leading to hospital admission in the elderly].
AB  - Drug related problems represent an important problem in geriatric patients, and
      contribute to hospitalization in 15 to 30% of the admissions. In most cases this
      concerns adverse drug reactions (normal dose and overdose) but also drug therapy
      failures (e.g. undertreatment) are common. The main pharmacological classes
      involved are cardiovascular drugs and drugs for the central nervous system. Drug
      related problems can be prevented by regular medication review to decide if all
      drugs have to be continued, and to check for adverse drug reactions. Clinical
      pharmacists in hospitals can detect drug related problems (over-, under- and
      misuse using a systematic approach) and recommend changes to improve
      pharmacotherapy. The community pharmacist can help by elaborating drug schemes,
      by screening for medication interactions, and by resolving practical problems.

PMID- 25055455
TI  - Anthranoid-containing medicines and food supplements on the Belgian market: a
      comparative study.
AB  - Medicines and food supplements containing anthranoid herbal drug preparations
      were verified on identity of the herbal substance, content of total
      hydroxyanthracene glycosides and microbiological quality. All examined medicines
      complied with the fixed requirements whereas all food supplements deviated from 1
      or more of the criteria. The food supplements showed a large variability in
      quality and content.

PMID- 25055456
TI  - [Lixisenatide (Lyxumia), subcutaneous].

PMID- 25055457
TI  - Team training takes off as providers prepare for coordinated care.

PMID- 25055458
TI  - Some insurers proposing hefty hikes in premiums.

PMID- 25055459
TI  - Debt levels up due to low rates, looser conditions.

PMID- 25055460
TI  - Kindred bid for Gentiva may signal budding post-acute consolidation.

PMID- 25055461
TI  - Rural hospitals get creative in staffing for IT needs.

PMID- 25055462
TI  - Statins on trial. Pfizer faces clot of lawsuits that claim Lipitor caused women's
      diabetes.

PMID- 25055463
TI  - The biggest boulder on the road to value.

PMID- 25055464
TI  - Dysfunction offers opportunity.

PMID- 25055465
TI  - Teamwork key to reducing lab-results errors.

PMID- 25055466
TI  - ACA is focus of HFMA gathering.

PMID- 25055467
TI  - Merger helps Baylor Scott & White get where it wants to be.

PMID- 25055468
TI  - [Musculoskeletal pain affects every other patient in Switzerland].

PMID- 25055469
TI  - [Medicine and pain: history of a relationship].
AB  - The vagueness surrounding the terms "suffering" and "pain" invites us to reflect
      upon the relationships between a physiological fact and a constitutive dimension
      of the human experience. History shows a constant medical preoccupation facing
      pain as a clinical symptom, endowed with a rich terminology, many ways of
      relieving pain and speculations on its diagnostic value. In the contemporary era,
      pain is revealed as a proper scientific object. This development accompanies an
      evolution of medical practices on pain that, far from representing continuous
      progress, adopts rather uneven and sometimes surprising outlines. As a whole,
      medicine is characterised by an important ambivalence when confronting pain,
      valuating it as an useful auxiliary or on the contrary denying the painful
      experience.

PMID- 25055470
TI  - [Implication of cognitive control capacity in pain experience].
AB  - Chronic pain is often associated with several symptoms in various areas such as
      depression, irritability, attentional difficulties, or interpersonal distress.
      Evidence suggests that these comorbidities may be explained by a limited capacity
      of individuals to exert cognitive control on thoughts, emotions, or behaviors. A
      decrease of this capacity of control could contribute to the development and
      maintenance of chronic pain and its associated symptoms. Benefits of the
      cognitive-behavioral therapy in the treatment of chronic pain may be explained by
      learning efficient and less costly pain coping strategies in terms of cognitive
      control capacity.

PMID- 25055471
TI  - [Tratment of pain--the point of view of the rheumatologist].
AB  - From the point of view of the rheumatologist, the treatment of pain should be
      adjusted individually in accordance with medical principles based on the facts
      related to the relevant pathologies. This treatment includes conservative
      (medicinal and non-medicinal), interventional and surgical methods. The treatment
      does not just depend on the diagnosis, but also on the particular functional
      disability based on the ICF (International Classification of Functioning) and the
      level of polymorbidity. As rheumatology patients often have comorbidity, the
      choice of painkillers (NSAIDs, analgesics, opioids etc), immunosuppressants and
      physical therapy methods (physiotherapy, ergotherapy, etc) may be limited.

PMID- 25055472
TI  - [Use of NSAIDs in traumatology].
AB  - In traumatology, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used,
      due to their efficacy in controlling pain and safety profile. Nonetheless,
      experimental and retrospective studies about the use of NSAIDs in traumatology
      raise the question about a possible negative influence on bone remodeling through
      inhibition of prostaglandin synthesis. The results from these studies must be
      interpreted with caution, as bone repair can be influenced by several parameters.
      When used in the case of sprains or tendinitis, unwanted side effects of NSAIDs
      seem to be limited; on the other hand, benefits in terms of antalgic effect are
      less clear. We have conducted a review of the literature aimed to suggest
      practical solutions for the use of NSAIDs in traumatology.

PMID- 25055473
TI  - [Acute analgesia: implementation of a dedicated protocol in an emergency
      department].
AB  - Acute pain relief is an ongoing challenge for both nurses and emergency
      physicians. Its management remains suboptimal or delayed, despite the existence
      of valid recommendations. The complexity of the emergency department and the
      diversity of encountered situations justify a tailored approach, taking into
      account the patient's clinical characteristics and needs. Such an approach must,
      under safety conditions assign sufficient autonomy to care providers in order to
      achieve pain relief. The benefits of an optimal analgesia are numerous. They
      include a greater patient satisfaction, a reduced length of stay, and a rapid
      return to mobility. This article highlights the key elements of acute pain
      management in the emergency department of the Geneva University Hospitals.

PMID- 25055474
TI  - [Childrens' pain, a complex entity to be explored].
AB  - From unrecognized babies' pain, to new discoveries made on early emotional memory
      and sensory capacities, chronic pain in childhood remains a complex field still
      to be explored. Besides, the discovery of early fetal sensorial receptions is an
      opening to new understanding of the origin of psychological chronic pain from
      early childhood to adolescence. From the silent babies suffering of emotional
      regulation disorder to adolescents' chronic recurrent pains, a common point is
      the expression of a psychic disease through the body. Different therapeutic
      actions are described, because without treatment chronic or recurrent pains may
      lead to a real risk of intellectual, affective and drive impoverishment for the
      suffering child.

PMID- 25055475
TI  - [Ischemic stroke: the cardiac workup].
AB  - The cardiac workup of stroke often includes a 24 hours Holter and an
      echocardiography looking for cardiac sources of emboli (atrial fibrillation (AF),
      intracardiac thrombus, mitral stenosis, recent myocardial infarction,
      endocarditis, dilated cardiomyopathy...) which would lead to a change of
      treatment (secondary prevention) aiming at decreasing the risk of recurrence. In
      case of a stroke with AF, the secondary prevention strategy is well defined
      (anticoagulants). It is less clear for the other causes. The diagnostic yield of
      these examinations is limited and there is a lack of consensus in their utility.
      This systematic review tries to sum up current guidelines. It appears that these
      examinations should rather be targeted than performed systematically.

PMID- 25055476
TI  - [The obesity paradox].
AB  - In general population, cardiovascular (CV) mortality increases in parallel with
      obesity severity, determined by body mass index (BMI). However in cohorts of
      patients with coronary diseases or heart failure a decrease of the global
      mortality has been observed in patients aged more than 65 years old with moderate
      obesity (BMI = 30-35) compared to normal weight people (BMI = 20-25) and morbid
      obese (BMI > 35). This "obesity paradox" could result from the selection of obese
      people with healthy metabolic profile and way of life. BMI does not allow to
      distinguish lean body mass from fat mass and therefore to evaluate abdominal
      obesity which is associated with metabolic syndrome and CV risk.

PMID- 25055477
TI  - [Interdisciplinary care for a patient suffering from Diogenes syndrome].
AB  - Interdisciplinarity is the combined care of a patient by two or more healthcare
      professionals. Taking into account the contribution of the different healthcare
      partners improves patient follow-up, quality of the care and use of resources.
      General practitioner (GP) becomes the pivot of a combined interdisciplinary
      ambulatory care allowing a prolonged staying at home and avoiding the
      multiplication of care offers. This paper, by the clinical description of a
      patient suffering from Diogenes Syndrome, allows a cross of the care between the
      GP, home nurse and pharmacist. It deals with follow-up questions, acceptance,
      objectives of treatment, communication between healthcare partners and "false
      notes" in the follow-up.

PMID- 25055478
TI  - [French research on human embryo: lots of noise for next to nothing?].

PMID- 25055479
TI  - [Who does what?].

PMID- 25055480
TI  - [Deep venous thrombosis in upper limbs: a new algorithm?].

PMID- 25055481
TI  - [The affair "Crispr-Cas9" or genetically enhanced humanity].

PMID- 25055482
TI  - [A moderate alcohol consumption decreases the risk of rheumatoid polyarthritis].

PMID- 25055483
TI  - [Parkinson, what's new? L-Dopa, The Lancet answers].

PMID- 25055484
TI  - [Adolescents, the courage of frank speech].

PMID- 25055485
TI  - [Procalcitonin as a predictor of bacteremia in postoperative cardiosurgery
      patients].
AB  - PURPOSE OF THE STUDY: To define diagnostics ability of procalcitonin (PCT) test
      for prediction of bacteremia of different etiology in cardio-surgical patients.
      MATERIALS AND METHODS: 10158 pairs of blood examples from cardio-surgical
      patients in early postoperative period were studied from 2007 to 2012. Results of
      PCT test were compared with blood cultures. The data is presented as absolute
      values and proportions. Furthermore a mean and standard error of the mean is
      presented. Differences in compared groups with p < 0.05 are considered
      statistically significant. RESULTS: In average a bacteremia occurred on a 6th day
      of postoperative period. Frequency of the positive blood cultures was 20.7%. 972
      cases of bacteremia (46.2%) was caused by Gram-positive cocci, 702 cases (33.3%)
      by Gram-negative bacteria and 338 (16.1%) by yeast-like fungi. Mixt-cultures were
      defined in 93 cases (4.4%). Monocultural bacteremia was analyzed only (n = 2012).
      Average level of PCT was higher (statistically significant) in cases with blood
      cultures than in cases without it (14.35 +/- 0.91 ng per ml vs. 7.35 +/- 0.26 ng
      per ml, p = 0). The highest PCT was fixed in cases of bacteremia caused by Gram
      negative bacteria (26.03 +/- 2.13 ng per ml). There was no significant difference
      between bacteremia due to enterobacteria and non-fermenting agents (30.56 +/-
      4.05 ng per ml u 22.79 +/- 0.21 ng per ml, p = 0.07). Statistically significant
      differences according to the average PCT were defined between bacteremia caused
      by Gram-negative bacteria (26.03 +/- 2.13 ng per ml), Gram-positive cocci (7.24
      +/- 0.88 ng per ml, p = 0), Candida species (9.02 +/- 1.84 ng per ml, p = 0), and
      cases of contamination (9.92 +/- 2.79 ng per ml, p = 0). Average PCT was not
      significantly different in cases of bacteremia due to coagulase-negative
      staphylococci (5.94 +/- 0.87 ng per ml), S. aureus (4.04 +/- 0.9 ng per ml),
      enterococci (15.72 +/- 3.52 ng per ml), Candida species (9.02 +/- 1.84 ng per
      ml), in cases of contamination (9.92 +/- 2.79 ng per ml) and in cases of the
      negative blood cultures (7.35 +/- 0.26 ng per ml). According to ROC-analysis the
      optimal cut-off point for PCT as a predictor of Gram-negative bacteremia was 2.47
      ng per ml, AUC 0.7 (95% DI 0.68-0.72). Index of sensitivity was 64%. CONCLUSIONS:
      PCT level in blood plasma of patients with bacteremia higher (statistically
      significant) than in patients with negative blood cultures. Gram-negative
      infection is more likely in cases when PCT higher than 2.47 ng per ml.

PMID- 25055486
TI  - [Risk factors of postoperative meningitis in patients with chiasm-sellar tumors].
AB  - Postoperative intracranial infectious complications are one of the most topical
      problems of neurosurgical intensive care due to theirs significant capability to
      impair outcomes of the main disease. PURPOSE OF THE STUDY: To define the risk
      factors of postoperative meningitis in patients with chiasm-sellar tumors.
      RESEARCH OBJECTIVES: 1. to define the effect of somatic and intracranial risk
      factors on occurrence of postoperative meningitis in patients after
      transsphenoidal and transcranial approaches to the tumor. 2. To define the effect
      of postoperative meningitis on outcomes of treatment in patients after
      transsphenoidal and transcranial approaches to the tumor. MATERIALS AND METHODS:
      Somatic and intracranial risk factors of occurrence of postoperative meningitis
      (pneumonia, urinary tract infection, sepsis, intra-abdominal hypertension, the
      presence of external ventricular and lumbar drainage, monitoring of intracranial
      pressure, cerebrospinal fluid, and reoperation) were fixed every day. The study
      was conducted in the ICU of the Burdenko from October, 2010 to July, 2012. The 34
      patients (19 males, 15 females) were included in the study (average age 47.5
      years). The patients were divided into two groups; 17 patients each group. The
      group-1 included patients after transcranial approach to the tumor and the group
      2 included patients after transsphenoidal approach. RESULTS: In the group-1 a
      meningitis occurred in 3 patients (17.6% +/- 9.2%, DI [-0.4 - 35.6]). In the
      group-2 a meningitis occurred in 7 patients (41.2% +/- 11.9) DI 95% [17.8 -
      64.4]. Accumulation of cerebrospinal fluid under the skin flap authentically
      increased a risk of a meningitis occurrence in patients after transcranial
      approach to the tumor (p = 0.031). There was no defined statistical significance
      of other risk factors. But there was defined a trend of the increasing of
      meningitis occurrence in patients after transsphenoidal approach in case of
      lumbar drainage or reoperation. Duration of mechanical ventilation and ICU stay
      in patients with meningitis was authentically longer than in patients without
      meningitis in both groups. In the group-2 the duration of mechanical ventilation
      and ICU stay was significantly shorter than in the group-1. CONCLUSIONS:
      Meningitis is not a typical complication of postoperative period in patients with
      transcranial approach to the tumor. After transsphenoidal approach a meningitis
      occurrence is likely in case of postoperative liquorrhea, lumbar drainage or
      reoperation. Subcutaneous accumulation of cerebrospinal fluid is a single defined
      statistically significant risk factor of meningitis. Postoperative meningitis
      impairs a condition of patients with chiasm-sellar tumors, increases the duration
      of mechanical ventilation and impairs treatment outcomes.

PMID- 25055487
TI  - [Changes in lipid and carbohydrate metabolism in patients with severe sepsis of
      different etiology].
AB  - Different origin (heterogeneity) of sepsis is a key stone in many discussions
      regarding options for the course and outcome, despite the general rules of
      development of the pathogenic mechanisms. PURPOSE OF THE STUDY: To compare data
      of systemic inflammation (CRP, PCT, IL-8, IL-6, IL-4, TNF-alpha) and markers of
      endothelial dysfunction (NO, lactate, D-dimers), also lipid (cholesterol,
      triglycerides, HDL, LDL, VLDL) and carbohydrate metabolism between the two groups
      of patients with severe intra-abdominal infection (n = 109) and severe sepsis of
      other etiologies (n = 53). RESULTS: We found out a significant difference between
      the groups in serum levels of the CRP, IL-4 and cholesterol at all stages of the
      study. During severe abdominal sepsis was accompanied by a significantly higher
      level of cholesterol, LDL and VLDL, as well as higher values of glycaemia.
      Patients with sepsis other etiology showed a lighter and more dynamic course of
      the disease was significantly lower 28-day mortality.

PMID- 25055488
TI  - [Significance of static pressure-volume loop for differential diagnostics and
      optimization of respiratory support in parenchimal respiratory failure].
AB  - PURPOSE OF THE STUDY: To determine significance of static pressure-volume loop
      (PV loop) for differential diagnostics of parenchymal respiratory failure,
      setting of positive end-expiratory pressure (PEEP) and recruit ability of the
      lung. MATERIALS AND METHODS: 76 patients (52 males) with parenchymal respiratory
      failure were included in the study (oxygenation index (PaO2/ FiO2) < 250 torr
      infiltrates on chest X-ray or CT-scan of the lungs, no data on left ventricular
      failure). We plot static PV loop by low flow technique in range of 0 to 40 mbar,
      fixing lower inflection point (LIP), linear compliance (Clin), upper inflection
      point (UIP), expiratory inflection point (EIP), compliance of linear deflation
      limb (C defl), hysteresis (Hyst) and volume of PEEP-induced recruitment of the
      lung (V(peep)). Then we plot another static PV loop with sustained inflation of
      40 mbar for 30 seconds, fixing changes in lung volume at 40 mbar. After 10
      minutes of sustained inflation we measured changes of oxygenation index. For 69
      patient we performed lung CT-scan and defined diffuse (acute respiratory distress
      syndrome) or local lung injury (pneumonia, atelectasis). RESULTS: LIP value can
      differentiate diffuse and local lung injury. LIP more than 10 mbar corresponds to
      diffuse lung injury on CT scan (sensitivity 76%, specificity 85%, AUROC 0.81).
      LIP cannot predict PEEP-induced alveolar recruitment and changes of PaO2/FiO2
      after sustained inflation maneuver (p > 0.05). Empirically set PEEP (by maximum
      PaO2/FiO2) was much higher than LIP (p < 0.0001), but LIP correlates with
      empirically set PEEP in diffuse lung injury (rho = 0.642, p = 0.003). Clin cannot
      differentiate diffuse from local lung injury (p > 0.05), but predicts PEEP
      induced alveolar recruitment during static PV loop plotting (rho = 0.493, p <
      0.0001). We did not find any statistically significant values of UIP and EIP for
      differential diagnosis, setting of PEEP or recruit ability of the lung.
      Hysteresis value (defined as volume difference at 20 mbar between deflation and
      inflation limbs) cannot predict influence of PEEP setting and sustained inflation
      maneuver on PaO2/FiO2 changes and recruit ability of the lung (p > 0.05). After
      static PV loop plotting combined with sustained inflation maneuver recruited
      volume of the lungs was 350 (250-450) ml. We didn't find significant differences
      between recruit ability of the diffuse and locally injured lungs (p > 0.05).
      Recruitment volume has no correlations with all points and segments of static PV
      loop. CONCLUSIONS: Static PV loop has limited prognostic value for differential
      diagnostics of diffuse or local lung injury and brings potential harm for setting
      PEEP according to LIP. LIP more than 10 mbar can predict diffuse lung injury.
      Clin can predict volume of PEEP-induced recruitment. In diffuse lung injury LIP
      correlates with empirically set PEEP.

PMID- 25055489
TI  - [Trends in world science and practice of pain treatment].
AB  - In recent days there are two main conceptions of the treatment of strong pain.
      The first conception is a system multimodal analgesia and the second is a
      multidisciplinary therapy including invasive techniques (local nervous blockades,
      neuroaxial blockades, neurostimulating or drug therapy with implanted systems
      etc.), physical, manual, and psychological effecting on peripheral and central
      nervous system. A physician (anaesthesiologist, oncologist, neurologist etc.)
      treats the pain according to interests of a patient. Multidisciplinary pain
      treatment, which is recommended by the American Pain Association, requires the
      use of special equipment for effecting on nervous system of the patient and
      contains conflict of interests of managers, medical workers, equipment providing
      companies and other parts of the multidisciplinary process. Therefore there is a
      risk that commercial benefit can get a main role in the process of pain
      treatment, but not interests of the patient. The "industrial" approach in the
      pain treatment is connected with many negative outcomes such as a minimizing of
      the role of pain science, increasing of complications risks due to invasive
      techniques of the pain relief etc. Therefore an objective analysis of pain
      treatment outcomes is needed Helsinki Declaration of a patient safety in surgery
      approved by European Society of Anaesthesiology in June, 2010 requires an
      accounting system of critical incidents, complications and assessment of outcomes
      in perioperative anaesthesiological practice. The same study is very actual for
      Russia especially to compare a safety of the system multimodal
      anaesthesia/analgesia and epidural blockades in major surgery.

PMID- 25055490
TI  - [Assessment of pain relief in patients receiving different variants of multimodal
      analgesia after major gynecological surgery].
AB  - The major gynecology surgery generally results in severe postoperative pain.
      Currently multimodal analgesia concept is widely used for the aim of
      postoperative pain relief optimization. According to this theory it is worth
      using the medication with different mechanism in order to increase analgesia
      qualify, decrease analgesic consumption and avoid adverse reaction. Unfortunately
      the surveys recently conducted have been pointed out the postoperative analgesia
      quality is still insufficient despite of using the concept mentioned above. One
      way to solve the problem is appearing in daily practice nefopam--centrally acting
      non-opioid analgesic that inhibits reuptake of serotonin, norepinephrine, and
      dopamine and also mitigates glutamatergic neurotransmission. In this trial we
      tried to assess the postoperative daily used analgesia quality and potency of
      preemptive multimodal analgesia model consisted of nefopam, ketoprofen,
      paracetamol and morphine.

PMID- 25055491
TI  - [Comparison of dexmedetomidine and propofol for short-term sedation in early
      postoperative period after cardiac surgery].
AB  - PURPOSE OF THE STUDY: To compare the efficacy of Dexmedetomidine and Propofol for
      short-term controlled sedation and analgesia in the early postoperative period
      after cardiac surgery. METHODS: We performed open randomized prospective
      comparative study in 55 cardiovascular surgery patients. In the early
      postoperative period 28 patients received infusion of Dexmedetomidine (0.2-0.7
      microg/kg per hour) while 27 patients--Propofol (0.3-2(system text of symbol)).
      Analgesia was carried out with Ketoprofen 100 mg/12h and additional 20 mg of
      Trimeperidine in case of pain intensity > or = 3 points (5-level verbal pain
      score). Sedation and agitation level (RASS scale), speed of awakening (Aldrete
      score), duration of mechanical ventilation and stay in the ICU, need for
      additional opioid injections, type and frequency of side effects were evaluated.
      RESULTS: We didn't find any significant differences in the duration of mechanical
      ventilation or rate of awakening after the end of infusion between the groups.
      Dexmedetomidine in the majority of cases resulted in mild or moderate sedation,
      Propofol--in deeper level of sedation. Retrograde amnesia was reached
      significantly more often (p < 0.05) in Dexmetomedine group. The daily dose of
      Trimeperidine in Propofol group was significantly higher (8 mg and 18 mg on
      average, p = 0.02). Differences in side effects between the groups were noted-
      bradycardia (Dexmetomedine--10 (39%), Propofol--3 (11%), p = 0.004) arterial
      hypotension (Dexmetomedine--9 (32%), Propofol--15 (59%), p = 0.002) and general
      malaise (Dexmetomedine--2 (7%), Propofol--6 (24%), p = 0.001). The length of stay
      in the ICU in Dexmetomedine group was significantly lower (1,1 days vs 2,6 days
      respectively, p = 0.006). CONCLUSIONS: To compare with Propofol Dexmetomedine
      induces less sedation level and more often provides retrograde amnesia with the
      same duration of mechanical ventilation and awakening rate. Dexmetomedine
      provides its own analgesic effect and shortens the length of patient's stay in
      ICU. Bradycardia was noted more frequently in Dexmedetomidine while arterial
      hypotension, general malaise and delirium--in Propofol group.

PMID- 25055492
TI  - [Role of migraine history in the development of postoperative nausea and vomiting
      in patients undergoing general and combined general-epidural anesthesia].
AB  - PURPOSE OF THE STUDY: To assess the role of migraine history in the development
      of postoperative nausea and vomiting (PONV) in patients undergoing general and
      combined general-epidural anaesthesia. MATERIALS AND METHODS: 127 women with
      oncogynecological pathology were randomized into 3 groups according to
      anaesthesia method. Patients of the group C (comparative group; n = 43; 18 with
      migraine) received general anaesthesia. Patients of the Group CA (n = 40; 19 with
      migraine) received combined general-epidural anaesthesia. Patients of the group D
      (n = 44; 19 with migraine) received general anaesthesia with adding of
      Droperidolum. All patients received standard prophylactics of PONV- Ondansetronum
      8 mg and dexamethasone 8 mg intravenous. RESULTS: In the group C a PONV occurred
      in 15 of 43 women (34.9%). PONV occurred in 6 of 18 women with migraine (33.3%)
      and in 9 of 25 women without migraine (36%). In the group CA a PONV occurred in
      10 of 40 women (25%). PONV occurred in 8 of 19 women with migraine (42.1%) and in
      2 of 21 women without migraine (9.5%; p = 0.036 in comparison with group C). In
      the group D a PONV occurred in 8 of 44 women (18.2%). PONV occurred in 1 of 19
      women with migraine (5.3% p = 0.03 in comparison with group C and p = 0.008 with
      group CA) and in 7 of 25 women without migraine (28%; there was no significant
      difference with groups C and CA). CONCLUSIONS: Migraine history is a significant
      risk factor of PONV. Epidural component of anaesthesia does not effect on
      frequency of PONV in women with migraine, but Droperidolum use allows increasing
      the frequency of PONV.

PMID- 25055493
TI  - [Features of maxillary and mandibular nerves imaging during stem regional
      blockades. From paresthesia to 3D-CT guidance].
AB  - There are difficulties in procedure of regional block of 2 and 3 brunches of the
      trigeminal nerve despite availability of many different methods of nerves
      imaging. The difficulties are connected with complex anatomy structure.
      Neurostimulation not always effective and as a rule, is accompanied with wrong
      interpretation of movement response on stimulation. The changing of the tactics
      on paraesthesia search improves the situation. The use of new methods of nerves
      imaging (3D-CT) also allows decreasing the frequency of fails during procedure of
      regional block of the brunches of the trigeminal nerve.

PMID- 25055494
TI  - [Application of exogenous surfactant and recruitment maneuver in newborns with
      respiratory distress-syndrome].
AB  - Respiratory distress-syndrome (RDS) in newborns is a one of the most frequent
      critical conditions of neonatal period requires the use of invasive methods of
      respiratory support. PURPOSE OF THE STUDY: To define an efficiency of complex
      application of exogenous surfactant and recruitment maneuver in newborns with
      RDS. MATERIALS AND METHODS: 30 newborns with RDS and progressive hypoxemia were
      included in the study. Average mass of body was 1575 grams. In 11 newborns RDS
      was accompanied severe hypoxemia and required the application of recruitment
      maneuver and exogenous surfactant administration. RESULTS: Application of
      recruitment maneuver with exogenous surfactant administration allow to improve
      gas exchange and blood oxygenation in newborns with RDS (PaO2 54 vs 39 mmHg; SpO2
      95 vs 90% and blood pH 7.34 vs 7.28). Application of recruitment maneuver with
      exogenous surfactant administration decrease number of complications and improve
      outcomes.

PMID- 25055495
TI  - [Comparative data about cryosupernatant and fresh frozen plasma use in treatment
      of disseminated intravascular coagulation in patients with generalized
      peritonitis].
AB  - PURPOSE OF THE STUDY: To compare the complex treatment of peritonitis with
      cryosupernatant and with fresh frozen plasma. MATERIALS AND METHODS: Outcomes of
      treatment were studied in 88 patients receiving cryosupernatant and in 112
      receiving fresh frozen plasma. RESULTS: Cryosupernatant application provides
      better dynamics of hemostasis, decreases a risk of thrombosis and mortality and
      improves outcomes of treatment. CONCLUSIONS: Cryosupernatant can be used instead
      of fresh frozen plasma in complex treatment of disseminated intravascular
      coagulation in patients with generalized peritonitis.

PMID- 25055496
TI  - [Causes and pathogenesis of hypocoagulation in reconstructive maxillofacial
      surgery].
AB  - Anaesthesia for reconstructive maxillofacial surgery can be accompanied with a
      significant hypocoagulation and blood loss. Possible causes of a hypocoagulation
      are dilution coagulopathy and disseminated intravascular coagulation.
      Coagulograms analysis showed that all patients have disturbances of blood
      clotting system. The main cause of a hypocoagulation is a disseminated
      intravascular coagulation.

PMID- 25055497
TI  - [Prophylaxis of blood loss and allogenic blood transfusion with fibrinolysis
      inhibitors produced in Russian Federation in patients undergoing cardiac
      surgery].
AB  - Significant bleeding during cardiac surgery, enough to cause re-exploration
      and/or blood transfusion, increases morbidity and mortality. Bleeding after
      cardiopulmonary bypass is related to multiple factors: endothelial dysfunction,
      thrombocytopenia, dilution coagulopathy. Hyperfibrinolysis is one of the
      important contributors to increased bleeding. To compare the effect of aprotinin
      with the effect of lysine analogues (aminomethylbenzoic acid and epsilon
      aminocaproic acid) examined 63 patients were divided into three equal groups
      depending on the product used for the prevention of activation of fibrinolysis.
      Data from rotational thromboelastometry measurements (Rotem Gamma Pentapharm,
      Germany), blood loss and transfusion were collected. The results confirm that
      used in the study antifibrinolytics: the lysine analogues aminomethylbenzoic acid
      and epsilon aminocaproic acid prevent hyperfibrinolysis after cardiopulmonary
      bypass as well as aprotinin.

PMID- 25055498
TI  - [Pulmonary artery catheterization in patients with blood diseases].
AB  - PURPOSE OF THE STUDY: To analyze complications of the pulmonary artery
      catheterization in patients with blood diseases. MATERIALS AND METHODS: 93 cases
      of pulmonary artery catheterization in patients with blood diseases were included
      in the retrospective study. RESULTS: Indications for pulmonary artery
      catheterization were septic shock (78.5%) and acute respiratory failure (21.5%).
      In 31 cases (33.3%) pulmonary artery catheterization was performed in conditions
      of agranulocytosis and in 81 cases (87%) in conditions of thrombocytopenia
      (platelets median 43 x 109 per liter minimal 7 x 109, maximal 150 x 109 per
      liter). Patients received transfusions of platelets in case of thrombocytopenia
      less than 30 x 109 per liter. Early complications of pulmonary artery
      catheterization occurred in 5 patients with thrombocytopenia (5.4%), the
      complications was connected with bleeding (hematoma, bleeding from place of
      puncture, lung bleeding) and mechanical (arterial puncture, pneumothorax,
      hemothorax). Number of attempts of the central vein catheterization was risk
      factor the complications. The frequency of catheter-associated sepsis was 5.89
      cases each 1000 catheter-days and the frequency of infections of the soft tissues
      was 9.78 cases each 1000 catheter-days. Catheter-associated infection
      complications occurred in cases of catheter use over 5 days. Catheter-associated
      sepsis occurred in 2 of 3 patients with agranulocytosis. Other complications
      included intermittent arrhythmias during catheter moving in the heart chambers
      (58), catheter balloon rupture (4), and thrombosis of catheter lumen (3).
      CONCLUSIONS: Pulmonary artery catheterization can be used in patients with blood
      diseases and first of all in cases of septic shock and acute respiratory failure.
      Alternative less invasive methods of monitoring should be used in patients with
      agranulocytosis.

PMID- 25055499
TI  - [Review of defects of anaesthesia and intensive care (based on fee of forensic
      medical examinations)].
AB  - The article deals with extremely topical problem of the patient safety in
      anaesthesiology and intensive care. The medical aid complications and defects
      issue in anaesthesiologist practice is not only specifically medical, but also
      social significant. The analysis of frequency and nature of defects in
      anaesthesiology and intensive care was conducted. It was based on 280 forensic
      medical examinations with anaesthesiologist as an expert. The acquired data
      showed that treatment defects were found in 63.7% of cases. Special attention was
      paid to airway management defects. Results helped to determine at which stage and
      procedure the critical incidents had occurred, as well as their frequency and
      causes. Considering the discovered causes of defects in anaesthesiology and
      intensive care, measures aimed at preventing complications and increasing the
      anaesthesiology and intensive care quality were proposed.

PMID- 25055500
TI  - [Intensive care and anaesthesia for blood loss in obstetrics. Clinical guidelines
      were approved by the Presidium of the Federation of Anaesthesiologists and
      Reanimatologists of Russia on 15/09/13 in Krasnoyarsk. Sectional commission in
      "Anesthesiology and Reanimatology" of the Ministry of Health of the Russian
      Federation approved the guidelines for submission to the Ministry of Health of
      the Russian Federation on 11/15/13].

PMID- 25055501
TI  - [Girgolav Semyon Semyonovich (1881-1957)].

PMID- 25055502
TI  - [Risk stratification in selective surgery of abdominal aortic aneurysm].
AB  - A retrospective analysis of data of 188 patients, who underwent a selective
      surgery for abdominal aortic aneurism showed, that all the patients had a cardiac
      pathology. Ischemic heart disease and arterial hypertension had 175 (93.0%) and
      177 (94.1%) of patients, respectively. Chronic nonspecific lung disease was noted
      in 65.4% patients and kidney disease--in 48.9%. Different complications developed
      in early postoperative period in 47 (25%) patients, that resulted in fatal
      outcome in 20(10,6%). The most frequent complication was an acute renal
      insufficiency, which led to fatal outcome in 40% patients. Myocardial infarction
      and pneumonia took the second place in the structure of postoperative
      complications, one half of the fatal cases was due to these. Retrospective risk
      stratification assessment of the development of early postoperative complications
      and lethality was made by Glasgow Aneurysm Score (GAS) and angiosurgical model
      scale V-POSSUM. It was stated, that score was up to 84 according to GAS scale and
      up to 28 (V-POSSUM). That fact is the evidence of high risk of the operation. On
      the basis of ROC curves building, the conclusion was made about greater
      predictive ability of V-POSSUM scoring system.

PMID- 25055503
TI  - [Acute pain syndrome and levels of peripheral blood saturation after various
      thoracic surgical approaches].
AB  - The traumatic effect of surgical approaches was determined by the intensity and
      duration of pain syndrome and by the degree of lung ventilation disturbances
      after thoracic surgery. An acute pain syndrome was considered by visual analog
      pain scale and a blood saturation level for the first 5 days after operation.
      There were 3 groups, each group consisted of 31 patients. All patients were after
      thoracotomies, thoracoscopies, rethoracoscopies. Maximal intensity of pain
      appeared to be after thoracotomies and its degree has been reducing since the
      first till fifth day (from 8.1 +/- 1.7 to 4.2 +/- 0.9 points). The pain syndrome
      was reliably less after thoracoscopy (from 5.9 +/- 1.6 to 3.5 +/- 1.4 points).
      Minimal pain was noted after revideothoracoscopies with the dynamics from 4.0 +/-
      2.4 to 2.7 +/- 1.2 points. The rate of blood saturation was more reduced after
      thoracotomy for the first two days till 92.9 +/- 4.6% and the saturation level
      became equal on the third day in all groups. Obtained data objectively confirmed
      the considerably less injury in the case of endoscopic thoracic approaches in
      comparison with open intervention.

PMID- 25055504
TI  - [To the question of reasonability of lung biopsy in primary spontaneous
      pneumothorax].
AB  - A biopsy of lung tissues was a conventional diagnostic method for detection of
      disseminated processes in the lung, which weren't diagnosed on preoperative
      stage. It was used during surgical anti-relapse treatment of spontaneous
      pneumothorax (SP). A retrospective analysis of the results of lung parenchyma
      biopsy was made in 143 patients, who have been operated for SP. Basic entry
      criteria of the research were: the age younger than 40 years old, a presence of
      one episode of spontaneous pneumothorax, an absence of complaints for respiratory
      organs before the development of the first episode of spontaneous pneumothorax.
      The biopsy with following pathomorphological investigation allowed a formulation
      of exact variant of disseminated processes, which gave the reason for the
      development of spontaneous pneumothorax in 9 (6%) patients out of 143. The
      presence of disseminated processes in the lung was detected with multispiral CT
      in all these patients on preoperative stage. The study of biopsy material found
      out the presence of emphysema of different degree of manifestation or fibrosis
      sites in the rest of the patients. An analysis of presented materials allowed the
      conclusion, that a performance of biopsy was indicated in the case of suspicion
      for lung disseminated processes in patients with SP. The biopsy with the
      following histological study didn't explain the reason of the development of
      emphysematous and fibrous changes in lung parenchyma in all other cases. At the
      same time, it didn't give the option for pathogenetic treatment and it wasn't
      possible to predict the following pathogenesis.

PMID- 25055505
TI  - [Thoracic endometriosis--the rare pathology in thoracic surgery].
AB  - Thoracic hematogenic endometriosis is a rare pathology. A clinical course hasn't
      pathognomic symptoms, because of it, the diagnosis is established due to
      histological study. The article presented two cases of female patients, who were
      suffering from thoracic endometriosis. They were hospitalized to the department
      of thoracic surgery of Municipal multifield hospital No 2 in Saint-Petersburg.
      The first patient had a posterior mediastinum tumor with asymptomatic disease
      course. The second patient was with recurrent catamenial pneumothorax.

PMID- 25055506
TI  - [Possibilities of surgery optimization for esophageal carcinoma in age-related
      aspect].
AB  - The article presents an experience of treatment of 180 patients with esophageal
      carcinoma. A resection of the esophagus with the gastric graft plasty was
      performed using original methods in 163 patients. There were 74 patients at a
      mature age and 89 patients at an elderly and senile age. The method of Doppler
      echocardiography was applied for the assessment of cardiovascular and respiratory
      systems. Results of surgery correlated with both groups. It allowed the
      recommendation of more wide application of surgical aids in elderly age group.
      Postoperative lethality consisted of 4.1% for mature patients and 10.1% for the
      patients at the elderly and senile age.

PMID- 25055507
TI  - [Prevention of side effects and complications after operation for partial ileal
      bypass].
AB  - Side effects and complications of the application of partial ileal bypass used
      for dislipidemia were analyzed in 162 patients with atherosclerosis. It was
      shown, that the partial ileal bypass operation could lead to the development of
      series of undesirable side effects such as diarrhea, hypovitaminosis B12, off
      state intestine enteritis. The application of modification of partial ileal
      bypass such as formation of ileo-ileoanastomosis 5-6 cm long near ileocecal valve
      with the maintenance of its functions disposed the diarrhea and minimized the
      risk of the development of hypovitaminosis B12 after operation. It is possible to
      prevent the development of enteritis of off-state loop of the small intestine by
      using microanastomosis between off-state and functioning iliac intestine. The
      partial ileal bypass operation didn't influence on body weight, wouldn't increase
      the risk of stone formation in the gallbladder and kidneys. The risk of the
      development of hypovitaminosis B12 is minimal after operation.

PMID- 25055508
TI  - [Hepatolithiasis].
AB  - The authors present an analysis of treatment results in 14 patients with
      hepatolithiasis. An influence of chronic opisthorchosis invasion on the frequency
      was determined. Hepatolithiasis was detected in 8 (0.14%) out of 5757 patients,
      who underwent the operation for cholelithiasis and its complications. The disease
      was found out in 6 (0.31%) patients out of 1965, who had cholelithiasis and
      accompanying chronic opisthorchosis. It was 2,2 times more frequent due to
      proliferative sclerotic changes of biliary system. The trasdermal teanshepatic
      cholangiography was contraindicated for opisthorchiasis injuries, because of the
      danger of subcapsular cholangioectates damage. The endoscopic retrograde
      cholangiopancreatography and the endopapillosphincterotomy were complicated due
      to extensive structures of the large duodenal papilla and distal section of the
      general bile duct. The patients were treated by using the cholecystectomy,
      extraction of stones from ducts, reconstruction of liver passage.
      Choledochoduodenostomy was performed with compulsory external drainage for ducts
      sanation from infections and helminthes in the case of the opisthorchiasis.
      Interportal infusions were carried out. The surgical, conservative and endoscopic
      treatment was required for multiple colangiolithiasis. The lethality consisted of
      7.1%.

PMID- 25055509
TI  - [Results of dynamic assessment of melatonin receptor expression in lymphocytes in
      patients with acute mild and severe pancreatitis].
AB  - The authors present results of the investigation of melatonin receptors
      expression in lymphocytes in dynamics in 102 patients with acute pancreatitis of
      mild and severe form and in 50 volunteers. A correlated analysis was made between
      obtained results of laboratory and instrumental researches and clinical course of
      acute pancreatitis. The decrease of MT1 receptors expression was noted on 25% in
      patients with acute pancreatitis. The decline of MT2 receptors expression was
      observed on 40% of patients with acute severe pancreatitis and in a case of acute
      mild pancreatitis--on 15.5%, respectively. Values of MT1 and MT2 expression were
      equal between healthy volunteers. The decline of MT2 expression was a prognostic
      unfavourable sign. Obtained results of dynamic expression assessment of MT
      receptors were presented as MT2/MT1 indices. Given index didn't change during
      disease, because of this, the index could be used as a prognostic development
      marker of destructive form of acute pancreatitis at the moment of patient's
      admission to hospital. Mean values of MT2/MT1 were determined for the purpose of
      universalization of used method (1.13 +/- 0.09 for mild form and 0.81 +/- 0.09
      for severe form of acute pancreatitis, respectively).

PMID- 25055510
TI  - [Intraoperative photon therapy in combination with mapping of motoric cerebral
      cortex in surgery of metastatic tumours of functionally significant zones of the
      large hemispheres of the brain].
AB  - Intraoperative radiation photon therapy (IORT) is a current effective technique
      based on the radiation exposure of extirpated tumor bed. This method is used in
      neurosurgery as a part of combined treatment of intracranial malignancies. The
      article presents the technique, an analysis of surgical treatment of 10 patients
      with cerebral metastases form of the lung and breast cancer, located in
      functionally important zones of the brain or nearby. IORT was performed using
      Carl Zeiss Intrabeam PRS 500(tm) system in combination with preoperative image
      guided transcranial motor cortex mapping carried on Nextim NBS. There weren't
      observed the intraoperative or postoperative complications.

PMID- 25055511
TI  - [Surgical correction of circulatory disturbance of the vertebral artery in trauma
      and degenerative diseases].
AB  - The article presents the results of examination and surgery of 185 patients with
      degenerative diseases as well as with a cervical spine trauma. The circulatory
      disturbance of the vertebral artery took place in all patients. A different
      degree of changes was observed in color duplex scanning. There were minor
      circulatory disturbances, course deformations (angular, C, S, V-shaped twists)
      and dissection of the vertebral artery. Color duplex scanning allowed estimating
      of local and system hemodynamic significance of extravasal influences. The
      strategy of treatment and volume of surgical interference were defined by the
      degree of circulatory disturbance in the vertebral artery.

PMID- 25055512
TI  - [Differentiated treatment of isolated traumatic injury of frontal lobes of the
      brain].
AB  - An analysis of treatment results was made in 83 patients with traumatic
      parenchymatous injuries of frontal lobes of the brain. Surgical interventions
      were performed in 31 patients and the conservative therapy was carried out in 52
      patients. Regular neurological examinations were completed for all the patients.
      The data of neurovisual methods were estimated. A strategy of treatment of
      frontal lobes injury depends on not only from the traumatic substratum volume,
      but at the same time, it is formed by clinical neurologic constellations and
      instrumental data in traumatic injury of frontal lobes of the brain. Risk factors
      of unfavorable effect of traumatic parenchymatous injury of frontal lobes of the
      brain were reflected in the initially low GCS score, a neurologic deficit
      progression with contusion haemorrhagic foci in the frontal lobe (volume greater
      than 25 cm3), a midline shift on 6 mm or more and signs of base cistern
      compression and presence of mass-effect, according to CT scan data. The developed
      algorithm could improve the results of treatment and makes better the quality of
      life of the patients with traumatic parenchymatous injuries of frontal lobes of
      the brain.

PMID- 25055513
TI  - [Features of clinical course of primary peritonitis in children].
AB  - The article presents an analysis of the features of primary peritonitis in
      children. Medical reports of 182 patients with primary and appendicular
      peritonitis were analyzed. It was significant, that the sick girls aged 4-7 years
      often had the primary peritonitis after acute inflammatory processes, which took
      place a month earlier. Chronic infection foci were noted in these patients. The
      age-specific features of maturation of the immune and reproductive systems
      predisposed the disease.

PMID- 25055514
TI  - [Long-term results of organo-safe operation in obstructive ureterohydronephrosis
      of terminal stage].
AB  - A comparative analysis of efficacy of two methods was the purpose of the
      research. Politano-Leadbetter technique was applied in 41 cases and nipple way
      was used in 13 cases. The investigation included 45 patients aged from 2 months
      till 17 years with congenital obstructive ureterohydronephrosis of terminal stage
      (the pathology was diagnosed from both sides in 15 children). A follow-up period
      was from 1 till 6 years. Recurrent intervention was required in 31 cases. An
      analysis of overall results allowed determining the outcome as positive in 26
      cases after Politano-Leadbetter operation. There were a vesicoureteral reflux in
      6 cases and signs of obstruction appeared in 9 cases. The application of nipple
      operation had positive results in 9 cases, at the same time, the complication
      such as vesicoureteral reflux was noted in 2 cases, the signs of obstruction were
      in 2 cases. The authors prefer using the nipple method of reimplantation in spite
      of identical results of two different methods.

PMID- 25055515
TI  - [Coronary collateral circulation in infarction-related artery in patients with
      acute myocardial infarction with rise and without rise of ST segment].
AB  - The authors analyzed a condition of coronary collateral circulation in infarction
      related artery in patients with acute myocardial infarction with rise and without
      rise of ST segment. The assessment of collateral circulation was made by coronary
      angiography using Rentop scale. Results of the research showed, that collateral
      circulation wasn't visualized by angiography in the first hours after acute
      myocardial infarction with the rise of ST segment. Apparently, this circulation
      didn't significantly assisted in maintenance of vital capacity of the myocardium
      in the pool of infarction-related occlusive coronary artery. Visualization of
      collateral circulation was noted in majority of patients with acute myocardial
      infarction without the rise of ST segment. Collateral flow was an important
      alternative source of blood supply of the heart in patients without rise of ST
      segment in the period of critical reduction of the antegrade blood flow.

PMID- 25055516
TI  - [Immediate results of surgical correction of combined pathology of the aortic
      valve and coronary arteries].
AB  - The authors analyzed an experience of surgical treatment in patients with aortic
      valve failure and ischemic heart disease. All patients have been operated in
      clinic of hospital surgery No 2 of State Pavlov Medical University. The work
      presented basic approaches to the management and strategy choice of the treatment
      of these patients. On the basis of given research, the authors suggested to
      perform a reconstruction of aortic valve by using original method in combination
      with coronary bypass surgery, which allowed avoiding a prosthetic-patient
      inadequacy. At the same time, it could improve an intracardiac haemodynamics and
      postoperative course.

PMID- 25055517
TI  - [Ultrasonic dissection and coagulation by attachment ("Harmonic Focus" in
      anatomic resection of the lung].
AB  - The authors aimed to evaluate the efficacy of application of ultrasound
      dissection technology and coagulation by using "Harmonic Focus" (HF) instrument,
      while performing anatomical resection of the lung in open thoracic surgery. The
      method was carried out in serial 20 patients with lung cancer, whom the lung
      anatomical resection was performed. A long attachment (17 cm) with curved
      branches was applied. There were 11 lobectomies and 9 pneumoectomies. The
      application of HF allowed the dissection of pleural adhesions, pulmonary
      ligament, a separation of roots of the lung elements, lymphatic nodes of roots of
      the lung and mediastinum, in spite of being very close to vessels. A fatty tissue
      of the mediastinum was removed quickly and practically without blood. The HF
      considerably accelerated the process of vessel treatment, especially, while
      performing the lobectomy. At the same time, the attempts of application of HF
      instrument for separation of interlobal fissure resulted in not quite
      satisfactory aerostasis and hemostasis. The duration of the lobectomy was 127 +/-
      35 minutes at the average and in the case of pneumoectomy, it consisted of 120 +/
      45 minutes. An intraoperative hemorrhage was 300 +/- 145 ml. A quantity of
      exudates was 440 +/- 280 ml by drainage on the first day. The pleural cavity
      drainage was used during 3 +/- 1 days. The HF instrument, which was applied for
      ultrasonic dissection and coagulation, was characterized by multifunctionality
      and simplicity of usage. It was recommended for a wide application in the
      thoracic surgery for performing the anatomical lung resections by thoracotomy
      method.

PMID- 25055518
TI  - [An application of low-invasive access in ultrasound-guided surgery of liquid
      formation of the abdominal cavity and retroperitoneal space].
AB  - The article presents a low-invasive method in the intraoperative ultrasound
      guided surgery. The method had several steps: an access (2-3 cm) was made to a
      liquid formation with the following aspiration of contents, a necrotic detritus
      was removed through the wound tract using simultaneous ultrasound examination of
      efficacy of emptying the cavity with drainage. This means allowed the performance
      of single-stage sanitization and drainage of cavity formations, which contained
      the liquid and dense necrotic tissues in the lumen. The method was effective,
      technically workable in any surgical hospital. At the same time, it was
      economically reasonable, because there wasn't need to buy an additional
      equipment. The application of the means considerably shortened a hospital stay
      and the lethality was reduced.

PMID- 25055519
TI  - [Efficacy of percutaneous trepan-biopsy in diagnostics of focal pancreatic
      lesions].

PMID- 25055520
TI  - [Priority of endovideosurgery in treatment of diffuse purulent peritonitis with
      subcompensated polyorgan dysfunction].
AB  - An analysis of treatment results was made in 474 patients with a diffuse purulent
      peritonitis. It was shown, that a dynamics of indices of computer
      phonoenterography (preservation and aggravation of disturbed intestinal motility
      pattern) and gas-liquid chromatography (the invariable or increased level of
      acetic, propionic, butyric acid in blood and exudate) significantly supported an
      evidence objectification to staged sanitization of the abdominal cavity.
      Recurrent peritoneal lavage was performed in a case of polyorgan dysfunction
      evidence in the stage of subcompensation in 36, 7 patients. It could be carried
      out by endovideosurgical method in 82.2% of medical supervisions. The lethality
      consisted of 4.9% in a case of the application of staged laparoscopic
      sanitization of the abdominal cavity in complex treatment of patients with
      diffuse purulent peritonitis.

PMID- 25055521
TI  - [The case of repeated operation for severe chronic constipation].

PMID- 25055522
TI  - [Management of medical care for the victims of road accidents in traumatology
      centers of Saint-Petersburg].
AB  - The number of road accidents, fatal outcomes and victims exceeded in 1.5 times in
      Saint-Petersburg in comparison with Moscow. At the average, 600 victims were
      treated in each of 6 first-level traumatology centers every year. The quantity of
      patients, who were admitted to 3 second-level traumatology centers, numbered 10
      times less. About 300 people entered to others hospitals. The lethality consisted
      of 15%, 20% and 37%, respectively. There are a lot of matters, that should be
      discussed, such as an importance of better treatment financing of multitrauma by
      using compulsory medical insurance system, an optimization of pre-admission
      treatment and a necessity of patient delivery by mobile medical team using the
      anaesthesiology and resuscitation.

PMID- 25055523
TI  - [Uglovsky readings (2nd Russian theoretical and practical conference with
      international participation "innovation in surgery" devoted to commemorating the
      109th anniversary of birthday of the academician F. G. Uglov, on 4 October, 2013,
      Saint-Petersburg)].

PMID- 25055524
TI  - [To the question of establishment history of thyroid gland surgery in Russia].

PMID- 25055525
TI  - [Professor Eskender Gafurovich Topuzov (to his 75th birthday)].

PMID- 25055526
TI  - [Results of surgical treatment of generalized emphysema of the lungs].
AB  - An analysis of examination and treatment results was made in 123 patients with
      generalized emphysema of the lungs and respiratory failure of II-III degree. The
      patients were divided into two groups according to the age: younger than 40 years
      old (group A - 9 patients),40 years old and older (group B - 114). A surgical
      reduction of lung volume was performed to correct the respiratory failure in 69
      patients. The rate of postoperative complications consisted of 14.7% in group A
      and it was 42.2% in group B.

PMID- 25055527
TI  - [Stenting of the oesophagus and oesophageal anastomoses in the case of neoplastic
      stenosis].
AB  - The authors aimed to optimize the strategy and technology of regeneration of
      oesophagus patency and oesophageal anastomosis in a case of tumor stenosis.
      Results of endoscopic correction of neoplastic stenosis of the oesophagus were
      studied in 244 patients, the cases of oesophagocolic anastomosis--in 12 patients
      and outcomes of oesophagogastric--in 8, respectively. A protection of self
      expandable stents is an effective method of regeneration of enteral feeding in
      patients with manifested dysphagia, which is specified by the growth of malignant
      tumor of the oesophagus or oesophageal anastomosis. A possibility of formation of
      broncho-esophageal communications limits the usage of silicone tubular and steel
      self-expandable stents with partial coating of a funnel by special indications: a
      disposition of proximal border of tumor stenosis less than 3 cm from esophageal-
      pharyngeal passage--for the first; a necessity of fast recovery of oesophagus
      patency in rigid stenosis and an impossible single-stage dilatation of
      constriction zone--for the second. An optimal device for oesophagus and
      anastomosis protection is a fiber-nitinol self-expandable stent with coating. The
      stents with antireflux valve should be used in the case of oesophagogastric
      passage lesions.

PMID- 25055528
TI  - [Ways of indication rise for operation in elderly and senile aged patients with
      stomach cancer].
AB  - An article presents an analysis of treatment of 113 patients (aged from 60 to 91
      years old) with stomach cancer. On this basis, an algorithm of examination of
      given age group was developed. Preoperative diagnostics wasn't directed only to
      an establishment of prevalence, a stage of main process. At the same time, it was
      aimed to determination and correction of accompanying somatic pathology, which
      required an application of multidisciplinary approach. An echocardiography was
      used for a functional condition assessment of cardiovascular and respiratory
      systems. The strategy allowed the indication rise for operation up to 96.5% in
      given group of patients.

PMID- 25055530
TI  - [Choice of surgical method of treatment of cholelithiasis].
AB  - This article presents results of surgical treatment of 2963 patients with
      cholelithiasis. The majority of them (71.8%) had an elective surgery, though
      28.2% of patients underwent an emergency operation. A comparative assessment of
      obligate treatment criteria was made in 2 groups. A first group consisted of 803
      patients and it was before introduction of Roman selection criteria used for
      surgical treatment of patients. A second group included 2963 patients in the
      period after introduction of selection criteria. Preoperative planning of surgery
      with evaluation of technical complexity of all stages of intervention with
      prognosis for possible complications should be the base of reasonable choice of
      surgical method of treatment of cholelithiasis and safety protection of surgery.
      The study completed and results obtained allowed decrease of the rate of
      postoperative complications to 1.4% and lethality--to 0.3%, respectively.

PMID- 25055529
TI  - [Efficacy of the use of remnant stomach in esophagoplasty].
AB  - In the period from 2001 till 2010 there were 117 extirpations of the oesophagus
      with single-stage plasty of the stomach in 94 patients and plasty of the large
      intestine--in 23 cases. Gastric resections were performed earlier in 50 (42.7%)
      patients, though gastrectomy took place in 39 (78%) patients. The accumulated
      experience allowed making an assessment of immediate and long-term results of
      esophagoplasty to patients, who had earlier the gastric resection. The
      incompetence of oesophagogastric anastomosis was noted in 2 times more frequent
      and the formation of stenosis of given anastomosis in 3 times more often. I order
      to improve the results of esophagoplasty, the method of serousmyotomy was applied
      in the cases of remnant stomach.

PMID- 25055531
TI  - [Endobiliary stenting with laparoscopic assistance--hybrid technology in
      complicated clinical situation].
AB  - The authors suggest an original method of endobiliary stenting with laparoscopic
      assistance for reduction of obstructive jaundice in patients with non-operative
      tumors of hepatopancreaduodenal zone in the case of impossibility of performance
      of percutaneous or endoscopic decompression of the bile ducts. A recanalization
      of tumor stricture was carried out with the aid of laparoscopic assistance. A
      self-expandable metal stent with polymeric covering was implanted in the bile
      ducts. The proposed method was applied in 5 cases. An adequate decompression of
      the bile ducts was noted in all cases. The patient's condition was good after
      surgery. There weren't any cases of serious complications or hospital lethality.

PMID- 25055532
TI  - [Effect of combined and local cytokine- and ozone therapy on the indices of lipid
      peroxidation, endogenous intoxication and ferroproteins in diffuse peritonitis].
AB  - The article analyzes the results of effect of combined and local cytokine- and
      ozone therapy on the indices of lipid peroxidation, endogenous intoxication and
      ferroproteins in 111 patients with diffuse peritonitis. It was shown, that
      combined sequential local and systemic cytokine and ozone therapy allows
      correcting the expression of endogenous intoxication and lipid peroxidation in
      diffuse peritonitis. This method suppresses an inflammation in the abdominal
      cavity. At the same time, it accelerates the elimination of intestine atony and
      thereby potentiates the possibilities of traditional methods of treatment.

PMID- 25055533
TI  - [Low-invasive surgery of diffuse peritonitis complicated by abdominal sepsis].
AB  - On the experience of treatment of 45 patients the efficacy of the programmed
      control sanation laparoscopy of the abdominal cavity was proved in postoperative
      period. This method had an advantage in comparison with open approach.
      Postoperative complications decreased from 50% to 28.8% (p < 0.05), the length of
      hospital stay and fatal outcomes reduced from 15.1% to 11.1% (p < 0.05). It was
      established by cardiointervalography, that laparoscopic methods of sanation
      reduced the degree of trauma during the intervention and prevented the adaptation
      mechanisms from tension and suppression of reserve compensatory possibilities of
      patient's organism.

PMID- 25055534
TI  - [Influence of immobilized forms of sodium hypochlorite on the immediate and long
      term results of treatment of the patients with diffuse peritonitis].
AB  - An analysis of complex examination and results of treatment was made in 290
      patients with diffuse peritonitis. The patients were divided into two groups
      according to way of sanation of the abdominal cavity. The sanation with 0.03%
      aqueous solution of sodium hypochlorite was used for the first group of 155
      patients. The immobilized forms of sodium hypochlorite in carboxymethyl cellulose
      gel were applied in the second group. The rate of postoperative complications was
      decreased on 15.4%, the lethality--on 8.2% in the case of application of the
      immobilized forms of sodium hypochlorite. The developed technology allowed
      increasing of physical component of life quality of the patients in 1.3 times,
      though it didn't influence on psychical component.

PMID- 25055535
TI  - [Results of surgical treatment of oral cavity cancer T1-2N0M0].
AB  - The article shows the results of treatment of 20 patients (aged from 46 to 85
      years old) with early oral cavity squamous cell carcinoma at the period from
      April 2009 to January 2011. The surgery included the resection of primary tumor
      and neck dissection in all the patients. The primary tumor was removed by mouth
      access in 10 patients and combined method was used in 10 cases. The selective
      neck dissection was carried out in 22 cases. The oral cavity wounds were closed
      primarily by local flaps in 10 patients, some small residual defects were left
      open in 3 cases. The reconstructions with remote skin-muscular infrahyoid flap
      were performed in 7 patients. The free revascularized radial skin-fascia flap was
      used in 3 cases. A follow-up period was from 24 to 44 months. The primary local
      regional control consisted of 85% in given group of patients. The rate of
      recurrence of the second primary metachronous tumor was 15%. Tumors were located
      in the oral cavity. Overall 3-year survival was 90% (18 out of 20 patients).

PMID- 25055536
TI  - [Immunological features of children with primary peritonitis].
AB  - An immunological research of the patients and control group with primary
      peritonitis was made. The main indices of immune response were in the range of
      age rates. However, the immune signs of foci of chronic inflammation were
      revealed in patients after operation. The consequences of disease (an abdominal
      cavity effusion) were eliminated during surgical interventions, but not the cause
      of the inflammation. Children with the primary peritonitis should be examined for
      detection of infection foci.

PMID- 25055537
TI  - [X-ray-morphological peculiarities of the long bones and reconstraction of their
      structure after elimination of knee joint deformation in children with
      hematogenous osteomyelitis consequences].
AB  - Roentgeno-morphological peculiarities of the bones forming the knee joint were
      studied in 47 patients with knee deformation caused by hematogenous osteomyelitis
      before and after treatment by the method of transosseous osteosynthesis. The
      stages of reconstruction of distraction regenerate were observed by radiography
      and computed tomography methods.

PMID- 25055538
TI  - [Modern methods of low-invasive treatment of the stricture and damage of the
      pancreatic duct, pancreatolithiasis].
AB  - The authors analyzed the experience of diagnostics and treatment of 49 patients.
      It was shown, that low-invasive methods of treatment (the endoscopic
      lithoextraction, stenting, surgical drainage) should be the priority means in
      treatment of pancreatolithiasis, strictures and cases of the pancreatic duct
      damage. The lethality consisted of 2.04% in these interventions.

PMID- 25055539
TI  - [The operative cystoscope with joystick control mechanism of flexible tools
      inserted into the urinary bladder and the ureter].
AB  - The authors developed an operative cystoscope with joystick control mechanism of
      ureter catheters and other flexible tools. This construction allowed control of
      flexible tools inserted into the bladder and the ureter in various directions,
      thus providing a necessary observation of the operative field at endoscopic
      operations on the bladder and ureter. This was one of the factors, which
      determined the operation success.

PMID- 25055540
TI  - [Rupture of myocardium with cardiac tamponade in nonpenetrating wound of the
      breast from traumatic weapon].

PMID- 25055541
TI  - [Surgical treatment of patients with combination of typical carcinoid and active
      tuberculosis of the lungs].

PMID- 25055542
TI  - [Rare observation of giant trichobezoar of the stomach, duodenum and jejunum].

PMID- 25055543
TI  - [Immature teratoma of the thyroid glands in 10 months old child].

PMID- 25055544
TI  - [Russian classification edition of complications in surgery].

PMID- 25055545
TI  - [Possibilities of transfusion therapy in surgical practice].
AB  - The up-to-date possibilities of transfusion therapy are presented in the article.
      The authors analyzed their own experience and made a review of literature. The
      study considers the mechanisms of treatment, immunological and infectious risks,
      indications and contraindications for application of transfusion therapy in
      surgical practice.

PMID- 25055546
TI  - [Clinical-epidemiological aspects of gastric and duodenum ulcer].
AB  - An analysis of reporting and statistical data showed the considerable changes in
      clinical-epidemiological indices of gastric and duodenum ulcer at the period from
      1998 to 2012. The prevalence of the disease and the number of primary patients
      decreased in 2-3 times. The reduction of the rate of perforations and ulcerous
      bleeding had been observed. However, the authors noted, that a tendency of
      frequency of occurrence increased and efficacy indices reduced in the last years.
      The rate of postoperative lethality raised in the cases of perforated ulcer. On
      this basis, the authors recommend to reconsider the existing opinion about
      further extension of out-patient treatment of patients with given pathology.

PMID- 25055547
TI  - [Professor Vadim Alekseevich Kornilov (1937-1993)--one of founders of the theory
      of vascular trauma].

PMID- 25055548
TI  - [Conference "Treatment of surgical and cancer patients in Saint-Petersburg"
      (19.11.2013, Saint-Petersburg)].

PMID- 25055549
TI  - [Cancerous pleurisy: the modern view on this problem].

PMID- 25055550
TI  - [Percutaneous puncture and endoscopic interventions in treatment of complicated
      chronic pancreatitis].

PMID- 25055551
TI  - [Fournier's gangrene--the actual aspects of old disease in the light of modern
      conceptions of pathogenesis].

PMID- 25055552
TI  - [Professor Mikhail Vasilievich Grinyov (commemorating the 85th anniversary of his
      birthday)].

PMID- 25055553
TI  - [Molecular biological characteristics of cancer].
AB  - The review presents the main and additional features that distinguish tumor cells
      from normal tissue cells. They include sustained proliferative signaling, evasion
      from growth suppressors, resisting cell death, enabling replicative immortality,
      angiogenesis induction, and invasion and metastasis activation. Basis for the
      formation of these features is provided by tumor genome instability. Tumors are
      complex tissues that consist of different cell types interacting with each other
      as well as with normal cells. An important characteristic of tumor cells is the
      ability to interact with the tumor microenvironment and the formation of tumor
      stroma.

PMID- 25055554
TI  - [Concomitant use of intravenous ozone therapy and small doses of direct current
      in the integrated treatment of patient with sterile pancreatonecrosis].
AB  - AIM: To estimate effectiveness of concomitant use of direct current in a small
      doses and intravenous ozone therapy in the integrated treatment of patients with
      sterile pancreatonecrosis. PATIENTS AND METHODS: 89 (39 women and 50 men, average
      age 48,2 +/- 3,6 years) Patient medical records, received a treatment for sterile
      pancreatonecrosis in surgery departments of Aktobe oblast were analyzed. In the
      period of 1997-2013, diagnosis of sterile pancreatonecrosis and its complication
      was found out on the basis of historical study, physical examination, clinical
      laboratory findings, ultrasound investigation and computerized tomography. All
      patients passed through complex basic conservative therapy and main group
      received also intravenous ozone therapy and small doses (20-25mkA) of direct
      current. RESULTS: Usage of small doses of direct current and intravenous ozone
      therapy in the integrated treatment of patients with sterile pancreatonecrosis
      helped on more rapid general well-being mend of patients. CONCLUSIONS: registered
      drop of transition frequency of sterile pancreatonecrosis into infected forms in
      3 times, reduction of patients period of stay at hospital in 1,6 times and
      mortality rates--in 1,3 times.

PMID- 25055555
TI  - [Urodynamic abnormalities in the kidneys of pancreonecrosis].
AB  - This paper presents experience in monitoring renal ultrasound data in patients
      with pancreatonecrosis from 20 to 60 years. It is also present two clinical cases
      of renal urodynamics in destructive forms of acute pancreatitis. Edematous form
      of acute pancreatitis and pancreatic cause violations not only secretion but also
      excretory function of the nephros. In patients with pancreatic necrosis
      accompanied by the formation of zones of limited fluid in the retroperitoneal
      space including retroperitoneal phlegmon may occur ureteral compression which is
      accompanied by appearance of urodynamic disorders in the nephros of varying
      severity. Ultrasound monitoring of renal care for patients with edematous form of
      acute pancreatitis, pancreatic necrosis helps to diagnose renal urodynamic
      disorders which allows timely corrected in the early stages of treatment
      activities in these patients and improve outcomes.

PMID- 25055556
TI  - [System analysis of metabolic profile of blood in patients with thermal trauma].
AB  - AIM: To make multiparametric analysis of blood metabolic profile in early period
      of burn disease. MATERIALS AND METHODS: We tested blood samples of 15 healthy
      adults (control group) and 60 patients with thermal trauma (main group--II-4IIIA,
      B degree of burn, more then 15 bsp). Parameters of lipid metabolism, level of
      glucose, lactate, malonic dialdehyde and some enzymes in blood plasma and
      erythrocytes were estimated. RESULTS: In early period of burn disease we fixed
      the clear metabolic disorders, including tissues hypoxia, activation of plasma
      transaminases and oxidoreductases, inhibition of detoxication system, induction
      of oxidative stress. Connection of metabolic changes, associated with burn
      disease, was registered. It supported by numerous correlations between studied
      parameters, formed from first day after trauma. CONCLUSIONS: Our data expand the
      knowledge about mating metabolic changes of catalytic activity of blood enzymes,
      forming in early period of burn disease (system metabolic disadaptation), and
      diagnostic value of some blood biochemical parameters in estimation of burned
      patient metabolism.

PMID- 25055557
TI  - [Adaptative resources of the main regulatory systems in patients with
      hypertension under the highland conditions].
AB  - AIM: To study characteristics of hemodynamics, spectral analysis of heart rate
      variability (HRV) and their association with the total blood concentration of
      stable metabolites of nitric oxide (nitrites and nitrates) in patients with
      hypertension living in highlands. PATIENTS AND METHODS: 110 natives of the
      highlands of Elbrus region were examined. All of them were divided into 2 groups-
      with 2d stage of hypertension (n = 50) and conditionally healthy (n = 60. All the
      participants were performed routine examination under the conditions of hospitals
      and out-patient clinics. Moreover they were performed ECG, rhythm-cardiography,
      echo-CG evaluation of the blood pressure, renal and thyroid ultrasound and eye
      ground examination. The assessment of HRV was made. RESULTS: In the group of
      patients with hypertension there was decrease in the total power of HRV - TP, low
      frequency range--VLF, LF and high frequency range HF. The main characteristics of
      the central and intracardiac hemodynamics were significantly higher in patients
      with hypertension in decreasing of nitric oxide production. CONCLUSIONS: Reverse
      reliable correlations were established between low frequency values of HRV,
      morpho-functional characteristics of the left ventricle and blood concentration
      of nitric oxide in patients with hypertension.

PMID- 25055558
TI  - [Correlation between concentration of pathological cytokines and erythropoietin
      in patients with chronic heart failure with anemic syndrome].
AB  - AIM: To study correlation between concentration of pathological cytokines and
      erythropoietin inpatients with chronic heart failure anemic syndrome and also to
      prove importance of this communication for need of appointment erythropoietin
      excitants. PATIENTS AND METHODS: 94 patients with chronic heart failure of New
      York Heart Association (NYHA) class III-IV a left ventricular ejection fraction
      of 40% or less withanemia w ere idied in inveslain (58 males, 36 females). Anemia
      was detected when hemoglobin (b) was less than 120 g/l in males and less than in
      females. 46 patients received traditional treatment of CHF (I group) and 48
      patients were treated additionally with erythropoietin (EPO) (II group).
      Percutaneous EPO 50 IU monthly to patients without iron deficiency for a period
      of 6 months. Echocardiography parameters, plasma NT and pro-BNP, cytokines, EPO,
      feritin and 6-minute walking test were assessed at baseline and after treatment.
      RESULT: in patients with CHF and anemia in II group erythropoietin treatment
      increased Hb levels by 22.4% (p < 0.05) and erythropoietin serum levels by 29.3
      +/- 14.3 IU/ml (p < 0.001). Increased erythropoietin level was associated with
      decrease of cytokines levels: IL 1 by 36.6% (p < 0.001), IL 6 by 54.3% (p <
      0.05), TNF alpha by 48.3% (p < 0.05) compared with patients in I group. In
      erythropoietin-treated patients there is a significant increase of LVEF by 19.04%
      (p < 0.05) compared with patients from I group. A greater 6-minute distance
      walked on exercise testing increased by 76.6% (p < 0.05) after treatment with
      erythropoieitin. CONCLUSIONS: Correction of anemia in patients with chronic heart
      failure with percutaneous erythropoietin injections 50 IU monthly for 6 month
      period to improve erythropoietin deficit and cytokines aggression and associated
      anemia, symptoms and quaity of life.

PMID- 25055559
TI  - [Prolactin and serotonin].
AB  - An overview of the results of studies on prolactin (PRL) is given. The molecular
      and genetic characteristics of PRL and its receptor (PRLR) are presented. The
      PRLR polymorphism in patients with tumors of the breast is described. Synthesized
      analogues of human PRL inhibited its peripheral effects. The vegetative nervous
      system modulate PRL secretion. PRL is a risk factor for breast and prostate
      cancer. The signaling mechanisms of PRL and its possible clinical use in therapy
      of breast cancer are characterized.

PMID- 25055560
TI  - [Change of cardiac ino- and chronotropic functions in stressed animals with
      blockade of different NO-synthases].
AB  - AIM: To investigate the effect of long-term immobilization-painful stress on ino-
      and chronotropic functions of the heart with inhibition of various NO-synthases.
      MATERIALS AND METHODS: 30 female albino rats were taken. Blockers of NO-system
      were: aminoguanidine (50 mg/kg), (50 mg/kg) and NG-nitro-L-arginine methyl ester
      (10 mg/kg). Stress was modeled by suspending the animals for cervical dorsal skin
      fold for 24 hours. The functional reserves of the heart were studied using
      adrenoreactivity and isometric load tests. RESULTS: experiments showed that
      painful stress leads to a decrease of cardiac ino- and chronotropic functions
      which is observed in the reduction of increment dp/dt+, dp/dt-, LVP and HR during
      load tests in comparison to control group of intact animals. Selective blockade
      of nNOS with 7-Nitroindazole causes even greater decrease an increment indices of
      myocardial contractility and LVP in stressed animals during load tests. The most
      pronounced inhibition of inotropic function of the stressed animal's heart
      observed in the non-selective inhibition of NO-synthases by L-NAME.
      Administration of aminoguanidine to animals (inducible NOS blocker) before and
      after stress causes an increase of inotropic reserve of the heart, resulting in
      increased increment of myocardial contractility and relaxation findings, left
      ventricular pressure and heart rate during load tests, CONCLUSIONS: NO-ergic
      system plays a significant role in limiting of the negative stress effects on the
      contractile function of the heart.

PMID- 25055561
TI  - [Heart rate variability in untrained young men under different power loading
      modes].
AB  - AIM: To study features of variability of a rhythm of heart at unexercised young
      men under the influence of power loadings in the conditions of appication of
      certain training modes in the course of long occupations by athleticism. PATIENTS
      AND METHODS: 40 young men participated in ispections at the age of 19-20 years,
      not having contraindications for occupations with burdenings. Research of
      indicators training loading of both groups used by representatives in the course
      of occupations conducted a method of definition of an index of training loading
      in athleticism. For determination of values of indicators of the statistical and
      spectral analysis of a rhythm of Polar RS800CX cardiomonitor was used. Control of
      studied indicators at rest and after power loading carried out for 3months of
      occupations by athleticism with an interval in 1 month. RESULTS: Use in the
      course of occupations by athleticism of power loadings with large volume of work
      and low intensity considerably increases activity of the central mechanisms of
      neurohumoral regulation of a rhythm of heart due to decrease in panasympathetic
      activation of autonomous nervous system on sinusovy knot of heart, than loading
      of high intensity with a small volume of work. CONCLUSIONS: The result of long
      term adaptation to occupations by athleticism, in the conditions of different
      modes of loading, is characterized by existence of an ekonomization of
      functioning of cardiovascular system of the unexercised contingent.

PMID- 25055562
TI  - [Modern medical problems of microcirculation and hypoxic syndrome].
AB  - In this paper long known problems of microcirculation are shown, which were
      solved only during the last 40 years. They are concerned with the velocity and
      character of the capillary blood flow, the regulation of the capillary blood
      flow, the role of various vessels in the oxygen transport, the role of leukocytes
      in physiology and pathology of the capillary blood flow, with the special
      features of the function of lungs in supplying the whole organism with oxygen and
      with bioenergetic laws in the development of an organism adaptation to hypoxia.
      Here we considered a number of the most important medical problems of
      microcirculation and hypoxic syndrome. A relatively new factor in the capillary
      circulation is the fact that in the brain and heart capillaries there are sites
      with pO2 close to zero. They show that the capillary circulation has no central
      nervous regulation of the blood flow. The blood flow in these organs obeys only
      occasional oscillations. The new fact is that Krogh's rule about metabolism and
      oxygen exchange occurring only in the capillaries is abandoned. It is shown that
      almost 30% of consumed oxygen is delivered to the brain via arterioles, which
      changes our relation to the capillary circulation as a unique mechanism of the
      tissue supply with oxygen. The new fact is also the mass adhesion of leukocytes
      to the walls of microvessels, which results in the occlusion of the vessels
      followed by the development of the heart and brain ischemia. It was shown for the
      first time that contrary to previous ideas the alveoli in the lungs are supplied
      with blood from a powerful network of large microvessels from 20 to 50 microm in
      diameter rather than from thin arterioles. They make possible the passage of 6
      121 of the blood in the norm and during stressed muscle activity--up to 18-231 of
      blood per minute. The principle is substantiated that during hypoxia only normal
      supply of an organism with oxygen may result in a complete adaptation of an
      organism to the deficit of oxygen.

PMID- 25055563
TI  - [Food sensitization in children with Opisthorchis felineus invasion].
AB  - AIM: To determine the mechanism of food sensitization in children with chronic
      Opisthorchis felineus invasion. PATIENTS AND METHODS: During the epidemiological
      study the groups of patients (7-10 years) with chronic opisthorchiasis (n = 237)
      and children without chronic opisthorchiasis (n = 496) were formed. The
      investigation included interviewing of parents/guardians, measurement of total
      IgE, specific IgE to food allergens and component-resolved diagnostic, real-time
      PCR in stool samples. RESULTS: The chronic opisthorchiasis invasion in children
      is associated with reduced risk of food sensitization, compared with non-infected
      group (9.7 vs 16.94%, OR = 0.53; 95% CI 0.31-0.88; p = 0.01). Opisthorchiasis of
      high intensity negatively correlated with increased level of specific IgE to food
      allergens in serum (OR = 0.46; 95% CI 0.24-0.91; p = 0.023). The association
      between level of total IgE and intensity of opisthorchiasis combinated with food
      sensitization was found. The sensitization to allergens class I (cyp c1, cor a11,
      gal d2, pru p3) is more prevalent in patients with opisthorchiasis, in uninfected
      children the sensitization to bet v1-homologues (mal d1, pru p1, cor a1, ara h8)
      is most common. CONCLUSIONS: The epidemiological data on the effect of the
      Opisthorchis felineus invasion on mechanisms of food sensitization in children
      were obtained.

PMID- 25055564
TI  - [A new class of phenomena identified during the analysis of neural network of
      multidimensional data from patients with inflammatory lung diseases].
AB  - AIM: To apply the neural network analysis method of multi-data of patients with
      community-acquired pneumonia (CAP) to recognize the variability of their
      diagnoses and discovery of new analytical capabilities of NSA based on new
      methodological approaches of the meeting. MATERIALS AND METHODS: In this paper,
      we applied a new approach of neural network analysis of multivariate data,
      obtained based on clinical, laboratory and instrumental tests in 60 patients
      older than 65 years at various stages of the treatment of community-acquired
      pneumonia. Anthropometric data were used together with the results of
      immunological and immunochemical studies of blood serum of patients with
      community-acquired pneumonia who were in the acute phase of the disease. RESULTS:
      A new approach analysis of these data revealed the presence of characteristic
      groups of the biomarkers, which consist from a combination of a small number of
      the signs that are necessary and sufficient in the aggregate for accurate
      classification of diagnoses for patients. CONCLUSIONS: The presence of these
      symptoms characteristic series shows that we have discovered a new class of
      phenomena. These phenomena manifest themselves in the hidden relationships
      between the signs which included in these groups and are reflect features of the
      flow processes in the pathogenesis of inflammatory diseases of the lungs in
      different diagnostic areas. Their study can be an important and interesting in
      terms of understanding the many aspects of this disease.

PMID- 25055565
TI  - [Influence of prodigiozan-dependent comuton on the resistance of liver
      mitochondria against damage by protonofor].
AB  - An effector of tissue stress of hepatocytes, prodigiozan-dependent comuton (PDC),
      provokes deenergiezation of liver mitochondria, preloaded by Ca2+ ions. In this
      case a decrease of membrane potential (MP) and Ca2+ efflux by cyclosporine A
      sensitive mechanism of megapore is observed. If megapore is blocked by
      cyclosporin A, protonofor FCCP provoked decrease of MP and Ca2+ efflux by
      cyclosporin A-insensitive mechanism. It is shown that PDC increases resistance of
      mitochondria to mentioned protonofor action by inhibition of both these effects.
      An inhibitory action of PDC is realized by K+ and NADH-dependent mechanism. The
      effector of hepatocyte tissue stress, prodigiozan-dependent comuton (PDC), evokes
      deenergizing liver mitochondria preloaded with Ca2+, both membrane potential (MP)
      decrease and Ca2+ release in according to cyclosporine A-sensitive mechanism of
      megapore being observed. If megapore is blocked by cyclosporin A, protonophore
      FCCP reduces of MP and Ca2+ release in according to cyclosporin A-insensitive
      mechanism. PDC is shown to increase the resistance of mitochondria against
      protonophore action mentioned above by means of inhibition of both these effects.
      Inhibitory action of PDC is realized due to both K+ and NADH-dependent mechanism.
      Protective effect takes place only in intact mitochondria of these cells providig
      (on condition that) its megapore mechanism is not activated. Moreover, the
      results obtained are evidence of PDC can function as protector due to
      intensification of energy generation in damaged.

PMID- 25055566
TI  - [Comparative study of pharmacokinetics of ofloxacin in a free and niosomal forms
      in experiments on white mice when administered per os].
AB  - AIM: To study features of pharmacokinetics of ofloxacin as a part of anion
      PEGylated niosomes on a basis of sorbitan monostearate (Span 60) to experimental
      white mice per os. MATERIALS AND METHODS: Ofloxacin was entrapped in niosomes
      consisting of Span 60, cholesterol, PEG 4000 and dicetylphosphate. Sizes of
      niosomes estimated by means of probe microscopy. Efficiency of inclusion of an
      antibiotic in niosomes defined after removal of free drug by a centrifugation.
      The analysis of the quantitative contents of ofloxacin in samples carried out a
      method of a high performance liquid chromatography. RESULTS: We studied the main
      pharmacokinetic parameters of ofloxacin when used free and niosomal forms of
      antibiotic to experimental white mice per os. It is shown that use of oral
      niosomal forms leads to decrease of maximal concentration in serum and increase
      of ofloxacin half-life by 7,4 times in average compared to the free form. It is
      determined that bioavailability of ofloxacin in the niosomal form is 154%
      relative to the free form of the antibiotic. CONCLUSIONS: Niosomal
      microcontainers are perspective technology of encapsulation and the directe
      transport of antibacterial preparations through biological barriers. Using of
      niosomal formulation of ofloxacin is able to afford to increase considerably
      efficiency of treatment in comparison with a free form and significantly decrease
      negative effects of antibiotic therapy.

PMID- 25055567
TI  - [Regulation of melanogenesis in the dyschromia of skin].
AB  - AIM: To examine the role of immune, biochemical and hormonal factors in the
      regulation of melanogenesis in patients with chromatopathy. PATIENTS AND METHODS:
      We observed 226 patients with various forms dyschromia skin. Age of the patients
      was in the range of 16 to 55 years. The frequency of females (n = 157) prevailed
      over the male sex (n = 69) 2,3 times. The disease duration ranged from 3 weeks to
      12 years. For the study of melanogenesis in vitiligo, nevi and melasma were
      studied parameters of the immune, endocrine and lipid peroxidation--antioxidant
      system. RESULTS: Melanocytes are responsible for the change in concentration a
      chromatophorotropic hormone and adrenocorticotropic hormone (ACTH) decrease or
      increase melanogenesis. Activation process is also associated with UFOs.
      Comparison of the level of system components lipid peroxidation (LPO)-
      antioxidant system (AOS) suppressor (CD8 +) lymphocyte activity vitiligo patients
      showed that the most pronounced suppressive effect was observed in patients with
      high levels of lipid peroxidation. At the same time, patients with
      hyperpigmentation found a significant negative relationship with CD4+. It should
      be noted a negative relationship CD16(+)-lymphocytes with indicators pituitary-
      adrenal axis in patients Dyschromias (r = -0,318 vitiligo, r = -0,512, r = 
      0,4578--in nevi and melasma, respectively). CONCLUSIONS: The results showed that
      vitiliginozny process, especially actively expressed, proceeds with the
      intensification of lipid peroxidation processes, changes in the state of AOS and
      immunity. With the increased level of hyperpigmentation CD95(+)-cells led to a
      weakening of apoptosis and cause increase in the number of melanocytes. When
      there is insufficient apoptosis hyperpigmentation, hypopigmentation and when-
      excessive apoptosis. To find mechanisms regulating skin pigmentation necessary to
      determine a-chromatophorotropic hormone, adrenocorticotropic hormone and neutral
      endopeptidase.

PMID- 25055568
TI  - [Features of the sleep pattern during pregnancy].
AB  - AIM: To evaluate the qualitative characteristics of a sleep in pregnant women in
      the 3rd term of the physiological pregnancy by a questionnaire survey. MATERIALS
      AND METHODS: We have demonstrated questionnaire survey data of 400 pregnant women
      (mean age 27.5 +/- 8.2 years) in the 3rd term of pregnancy. Questioning conducted
      using the scale PSQI (PITTSBURGH SLEEP QUALITY INDEX--Pittsburgh Sleep Quality
      Assessment Questionnaire), EPWORTH SLEEPINESS SCALE (sleepiness questionnaire
      Epfort's) and screening questionnaire to identify obstructive sleep apnea.
      RESULTS: We have determined that 78% of pregnant women to complain about sleep
      disorders, namely obstructive sleep disordered breathing, insomnia, "restless
      legs" syndrome, and combinations thereof. The frequency of sleep disorders
      increases as pregnancy progresses. Obstructive sleep disordered breathing
      increases with 10.12% in the 1st term to 31.7% in the 3rd term, insomnia--from
      14.3% in the 1st term to 37.6% in the 3rd term. In pregnancy increases of sleep
      latency (from 14.3 to 44.9 minutes), and reduced the duration of a sleep (from
      8.7 to 7.8 hours). CONCLUSIONS: high frequency of sleep disorders in pregnancy
      requires early pathogenetic prevention of pathological conditions, both in the
      mother and in the fetus.

PMID- 25055569
TI  - [It is still painful!].

PMID- 25055570
TI  - [Nurses are a vital resource for health care].

PMID- 25055571
TI  - [Community involvement, the great national cause of 2014].

PMID- 25055572
TI  - [Standards and risks of peripherally inserted central catheters].

PMID- 25055573
TI  - [Advanced practice nurses unite].

PMID- 25055575
TI  - [Reinforcing hospital security protocols].

PMID- 25055574
TI  - [Vaccination obligations of nursing students].

PMID- 25055576
TI  - [Deprivation of liberty analyzed by the Controller General].

PMID- 25055577
TI  - [Reduction of nursing staff influences patient survival].

PMID- 25055578
TI  - [Sharing quality practices at the European level].

PMID- 25055579
TI  - [Patient rights].

PMID- 25055580
TI  - [Seven million annual deaths in the world are due to air pollution].

PMID- 25055581
TI  - [Encouraging the business of autonomy].

PMID- 25055582
TI  - [Ebola vigilance].

PMID- 25055583
TI  - [Eleven nursing projects rewarded by the Any d'Avray prize].

PMID- 25055584
TI  - [When pain cannot be expressed].
AB  - How pain is felt is a personal and private fact which is almost impossible to
      measure, which eludes any attempt to grasp and describe it and any desire to
      convey to another person its intensity and its nature. The challenge is to
      understand the pain, to assess it and manage it.

PMID- 25055585
TI  - [A mental health multidisciplinary team for pain and somatic care].
AB  - Patients suffering from mental illness or pervasive developmental disorders often
      resist examination and treatment. The Regional pain and somatic care in mental
      health centre of the Etampes public health institute (EPS) uses gas and air when
      carrying out nursing procedures. The nurses support patients with compassion,
      attentive to any nonverbal indication of pain.

PMID- 25055586
TI  - [Pain and coma].
AB  - Pain is a complex notion which caregivers must be able to decipher. Its aspects
      vary depending on the patient's condition. In cases of verbal communication
      disorders, the subjectivity of the caregiver is enlisted. How should pain be
      assessed in situations of coma and how should it be treated?

PMID- 25055587
TI  - [Pain and the patient care team in intensive care].
AB  - Pain is an indicator of the quality of care, especially in intensive care. It
      gives rise to a questioning of practices. It requires formalised measures and
      standardised methods as well as a common language within the teams. The
      assessment and management of pain is multidisciplinary and responsibility is
      shared.

PMID- 25055588
TI  - [Pain, the elderly and verbal communication disorders].
AB  - The prevalence of pain increases with age and multiple pathologies. Care
      procedures and movement are often triggers: dressings, injections, perfusions,
      washing, changes, transfers, walking, meals, etc. Which tools should be used when
      speech is lacking? What are the challenges in geriatrics for the patient and the
      caregivers? How should we orient our observations or behavioural disorders in
      terms of pain, anxiety or dementia?

PMID- 25055589
TI  - [A pain assessment tool for patients with multiple disabilities].
AB  - In Hendaye hospital, a tool is used to study the expression of pain of multiply
      disabled people. The pain assessment scale for multiply disabled adolescents or
      adults (EDAAP) allows caregivers to detect situations of pain without the need
      for a medical presence.

PMID- 25055590
TI  - [Kidney transplant coordinator, a collaborative nursing practice].
AB  - A transplant nurse coordinator presents her missions, notably with living donors
      wishing to give their kidney to a relative or close friend. This therapeutic
      solution requires a specific medical and legal procedure before the transplant,
      at the heart of which the kidney transplant nurse coordinator plays an essential
      role.

PMID- 25055591
TI  - [Clinical examination of respiratory function].
AB  - The physical pulmonary examination consists of four stages: inspection,
      palpation, percussion and auscultation. Rarely used in current practice by French
      nurses, it is nevertheless an important part of the clinical examination of the
      respiratory function.

PMID- 25055592
TI  - [Medical transport, an essential element of infection control].
AB  - To reinforce hospital hygiene, Sartene general hospital uses tools for passing on
      information when patients are transferred by medical transport. These three
      communication sheets specify notably the type of extra precautions put in place
      to ensure that the staff in each department is correctly informed and can respect
      them.

PMID- 25055593
TI  - [The patient-centered approach, a humanistic pathway for care].
AB  - In Canada, hospitals focused on accounting and administration tend to neglect the
      notion of service. In order to improve the quality of service provided to the
      clientele and staff a change of philosophy is required. The customer-centric
      approach, developed by American companies such as Disney, could benefit the nurse
      patient relationship and relations between staff.

PMID- 25055594
TI  - [Nursing care of victims of sexual violence].
AB  - Sexual violence is a deeply dehumanising experience. The forensic consultation
      with victims of sexual violence requires particular attention from caregivers so
      that it is not experienced as another assault. It requires considerable
      investment and availability. Quality care is a critical issue for the follow-up.
      The participation of the nurse in every stage of the care process is reassuring
      for the victim.

PMID- 25055595
TI  - [Discovering the mortuary during training].
AB  - The mortuary in Tenon hospital in Paris regularly receives trainee nurses and
      nursing auxiliaries. They discover the place, the practice of washing and
      preparing the deceased's body and learn how to support the families. The visit is
      an opportunity to face death and put any prejudices to one side.

PMID- 25055597
TI  - [Nursing care of an acute emotional crisis].

PMID- 25055596
TI  - [Drug therapy for type 2 diabetes].

PMID- 25055598
TI  - Emergency care for a patient with coronary heart disease.
AB  - Mr and Mrs Murphy, on holiday in France, are spending a few days in Paris before
      visiting the Chateaux of the Loire. Their holiday takes a frightening turn when
      Mr Murphy suffers a heart attack.

PMID- 25055599
TI  - [A six month international educational exchange].

PMID- 25055600
TI  - [Protected bronchoscopic sampling ].

PMID- 25055601
TI  - Delivering Better Oral Health 2014--what's new in the third edition?

PMID- 25055602
TI  - The extent of food advertising to children on Greek television: focus on foods
      potentially detrimental to oral health.
AB  - OBJECTIVES: To investigate the extent and nature of food advertising to children
      on Greek television, focusing on the adverts for foods with potential harmful
      effects on oral health, and to examine the persuasive marketing techniques used
      to promote food products. METHODS: Advertisements broadcast on six TV-channels
      during children's peak viewing times on two weekdays and two weekend days in the
      period May-June 2010 were recorded (166.7 hours). Each advertisement was coded
      according to: date, day, length, type of program in which the ad appeared, type
      of product advertised and promotional technique used. Food advertisements were
      subdivided according to their sugar and/or acid content as potentially harmful or
      non-harmful to teeth. RESULTS: Food advertisements had an average frequency of
      8.0 per hour during children's peak viewing times with highest frequency (11.4
      per hour) on weekends during child-focused programs. Of all advertisements, 1330
      (26.7%) were for foods, and 595 (44.7%) of these deemed to be potentially harmful
      to teeth. The most commonly advertised food product during children's programs
      was confectionery, 80 (27.7%). Of food advertisements, 199 (15.0%) used at least
      one of the promotional techniques likely to appeal to children. Advertisements
      for foods potentially harmful for teeth were more likely to be shown during child
      focused programs (OR 2.92, 95% CI 2.04-4.16) and to promise a free gift with
      purchase (OR 35.43, 95% CI 10.83-115.88). CONCLUSION: Children in Greece are
      exposed to a large volume of advertisements for unhealthy foods and drinks, which
      intensively use persuasive techniques proved to affect children's food
      preferences and consumption. Our study provides evidence that could support
      advocacy and interventions for the regulation of food advertising.

PMID- 25055604
TI  - Preventing caries in young children of immigrant Bangladeshi families in New
      York: perspectives of mothers and paediatricians.
AB  - OBJECTIVE: Childhood caries is common in South Asian immigrant families. Few
      children visit a dentist by 12 months, as recommended by current guidelines. The
      paediatric visit has important potential for linking children to preventive care.
      The aim of this study was to understand the barriers and facilitators to caries
      prevention for young children of immigrant Bangladeshi families in New York.
      Qualitative data were collected as a preliminary step in the development of an
      oral health counselling intervention for South Asian children. BASIC DESIGN:
      Qualitative interviews on child feeding and oral health prevention were conducted
      with Bangladeshi mothers. Qualitative interviews were conducted with
      paediatricians regarding their experiences with providing care. The data were
      analysed using standard qualitative approaches. SETTING: Paediatric practices
      serving low income Bangladeshi immigrants in New York City. PARTICIPANTS: 26
      mothers of children aged 6-24 months receiving services in five paediatric
      settings and 15 paediatricians providing care in these settings. RESULTS: Both
      mothers and their paediatricians described risky feeding practices, communication
      problems and a lack of compliance. Oral health for young children was a low
      priority for some mothers. Most, however, were concerned about childhood caries
      but lacked skills or resources to decrease caries risk. CONCLUSIONS: Results
      support our plan to develop an empowerment-based counselling intervention to
      address caries risk in children. Paediatric dentists should be aware of the
      barriers to caries prevention in this group.

PMID- 25055603
TI  - Parental views on delivering preventive advice to children referred for treatment
      of dental caries under general anaesthesia: a qualitative investigation.
AB  - OBJECTIVES: To: 1, Explore opinions of parents of children undergoing caries
      treatment under general anaesthesia (GA) regarding delivery of oral health
      advice; 2, Discover current oral health practices and beliefs; 3, Inform further
      research and action. METHODS: Qualitative study using semi-structured interviews
      and thematic data analysis, sampling parents of children aged 3-10 years
      undergoing GA tooth extraction due to dental caries. RESULTS: Twenty nine parents
      were interviewed (mean age 38.9 years, range 28-50, sd 6.4). The mean age of
      their children was seven years (range 3-10, sd 2.1). All children required
      deciduous tooth extractions (5.1 teeth on average). Those that also required
      permanent tooth extractions had on average 2.1 permanent teeth extracted. Many
      parents knew the importance of oral hygiene and sugar limitation, describing it
      as 'general knowledge' and 'common sense'. However, few understood that fruit
      juice is potentially cariogenic. Parenting challenges seemed to restrict their
      ability to control the child's diet and establish oral hygiene. Many reported not
      previously receiving oral health advice and reported never having fluoride
      varnish applied. There were requests for more caries prevention information and
      advice via the internet, schools or video games. CONCLUSION: Parental oral health
      knowledge, parenting skills, and previous advice received seem to all be issues
      related to the oral health of those children. Providing advice, especially in
      respect to fruit juice cariogenicity and the benefits of fluoride application
      through a child-friendly website, including a video game, as well as the use of
      school programmes might be an acceptable approach.

PMID- 25055605
TI  - Predicting geographically distributed adult dental decay in the greater Auckland
      region of New Zealand.
AB  - OBJECTIVE: To model the geographic distribution of current (and treated) dental
      decay on a high-resolution geographic basis for the Auckland region of New
      Zealand. BASIC RESEARCH DESIGN: The application of matrix-based mathematics to
      modelling adult dental disease-based on known population risk profiles to provide
      a detailed map of the dental caries distribution for the greater Auckland region.
      RESULTS: Of the 29 million teeth in adults in the region some 1.2 million (4%)
      are suffering decay whilst 7.2 million (25%) have previously suffered decay and
      are now restored. CONCLUSIONS: The model provides a high-resolution picture of
      where the disease burden lies geographically and presents to health planners a
      method for developing future service plans.

PMID- 25055606
TI  - Dentists' perspectives on caries-related treatment decisions.
AB  - OBJECTIVE: To assess the impact of patient risk status on Colombian dentists'
      caries related treatment decisions for early to intermediate caries lesions
      (ICDAS code 2 to 4). METHODS: A web-based questionnaire assessed dentists' views
      on the management of early/intermediate lesions. The questionnaire included
      questions on demographic characteristics, five clinical scenarios with randomised
      levels of caries risk, and two questions on different clinical and radiographic
      sets of images with different thresholds of caries. RESULTS: Questionnaires were
      completed by 439 dentists. For the two scenarios describing occlusal lesions
      ICDAS code 2, dentists chose to provide a preventive option in 63% and 60% of the
      cases. For the approximal lesion ICDAS code 2, 81% of the dentists chose to
      restore. The main findings of the binary logistic regression analysis for the
      clinical scenarios suggest that for the ICDAS code 2 occlusal lesions, the odds
      of a high caries risk patient having restorations is higher than for a low caries
      risk patient. For the questions describing different clinical thresholds of
      caries, most dentists would restore at ICDAS code 2 (55%) and for the question
      showing different radiographic thresholds images, 65% of dentists would intervene
      operatively at the inner half of enamel. No significant differences with respect
      to risk were found for these questions with the logistic regression. CONCLUSION:
      The results of this study indicate that Colombian dentists have not yet fully
      adopted non-invasive treatment for early caries lesions.

PMID- 25055607
TI  - Determinants and trends in dental expenditures in the adult US population:
      Medical Expenditure Panel Survey 1996-2006.
AB  - OBJECTIVES: To estimate dental expenditures in 2006, to analyse dental
      expenditures by potential explanatory factors for 2006 and to explore trends in
      dental expenditures from 1996-2006. METHODS: Medical Expenditure Panel Survey
      (MEPS) data were used. T-tests and analysis of variance were used to test for
      significance. Multivariable linear regression analysis was conducted to identify
      independent predictors of dental expenditures. The trend analysis was conducted
      for the 11-year period, 1996-2006, on adults aged 25 years and older.
      Expenditures were inflation adjusted to 2006 dollars using the annual average
      Consumer Price Index. Data were analysed using the MEPS query tool and SASv9.2.
      RESULTS: In the 2006 MEPS sample, 8,001 adults had dental expenditures and when
      weighted represented about 93 million non-institutionalised adult US civilians.
      The mean dental expenditures for this weighted sample were $611 (sd 1,309),
      median $233 (inter-quartile range 466). As expected, in 2006, dental expenditures
      increased with age. Those adults who reported their self-perceived health status
      as 'excellent' were observed to have lowest dental expenditures in this category.
      After adjusting for other variables in the multivariable linear regression
      analysis of dental expenditures, age, race/ethnicity, income, geographic
      location, perceived health status and dental insurance coverage remained
      significant. CONCLUSION: Dental expenditures for 2006 were $611 (mean) and $233
      (median). The time-trend showed substantial but non-uniform annual changes in
      real dental expenditures between 1996 and 2006.

PMID- 25055608
TI  - The caries experience of 5-year-old children in Scotland, Wales and England in
      2011-2012: reports of cross-sectional surveys using BASCD criteria.
AB  - OBJECTIVE: This paper collates differences in methods and trends in caries
      prevalence in surveys of the oral health of young children undertaken in
      Scotland, Wales and England in 2011-12. For Wales and England this was the second
      survey carried out since changes were required in consent arrangements. METHOD:
      In compliance with BASCD criteria representative samples were drawn within the
      geographies of primary care organisations across the UK, and within Local
      Authorities across England and Wales. Consent was sought in two ways; via opt-in
      parental consent in England and Wales and opt-out parental consent in Scotland.
      Children aged five were examined in England and those aged 5 to 6 were examined
      in Wales and Scotland. Examinations were conducted in schools by trained and
      calibrated examiners and caries was diagnosed at the dentinal threshold using
      visual criteria. RESULTS: In Scotland there is a continuing decline in caries
      prevalence in young school children. Comparison with the previous survey using
      positive consent in England and Wales shows a decline in caries in both England
      and Wales although decay levels remain higher in more deprived areas. CONCLUSION:
      International comparisons assist in interpreting data and trends even if there
      are some differences in approach. A trend line is more useful than a single data
      point for monitoring of oral health. This second survey using positive parental
      consent in England and Wales has enabled trend analysis for the first time since
      the consent arrangements changed.

PMID- 25055609
TI  - What are the most accurate predictors of caries in children aged 5 years in the
      UK?
AB  - OBJECTIVE: To find the most accurate indicators of the distribution of dental
      caries in 5-year-olds in the city of Sheffield, UK, using a conceptual framework
      based on the social determinants of health. METHOD: A list of structural and
      intermediary indicators was compiled based on the Commission on the Social
      Determinants of Health's (CSDH) conceptual framework. To quantify these
      indicators, existing data on dental caries were obtained from the NHS Dental
      Epidemiology Programme, while data on social position, education, employment,
      income, material circumstances, social cohesion, psychosocial factors and
      individual behaviours were obtained from the Public Health Intelligence Team at
      Sheffield City Council. These data were mapped onto a simplified framework of the
      social determinants of dental caries. Regression analysis was conducted on this
      simplified framework to determine the amount of variance each indicator
      contributed to the distribution of dental caries at neighbourhood level. RESULTS:
      The total score for the 2010 Index of Multiple Deprivation contributed a
      significant amount of variance (60.4%) compared to the combined variance of the
      other 13 indicators (70.5%). CONCLUSION: The total IMD score has the potential to
      be used as an indicator for the targeting of oral health improvement programmes
      where survey data are not available. A large prospective study is required in the
      UK to investigate the full range of factors in the CSDH model to develop a new
      index which might better predict dental caries experience than IMD.

PMID- 25055610
TI  - Bruxism and health related quality of life in southern Italy's prison inmates.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of self-assessed
      bruxism, the level of Health Related Quality of Life (HRQoL) and their
      relationship in a group of male inmates. BASIC RESEARCH DESIGN, SETTING: The
      present study was cross-sectional, its setting was two penal institutions in
      Italy. PARTICIPANTS: A sample of 280 male prisoners (mean age 39.7 years). Due to
      the very small number of female prisoners, it was not possible to study both
      genders. INTERVENTIONS AND MAIN OUTCOME MEASURES: Subjects were administered a
      questionnaire with items investigating demographic data, self-assessed bruxism
      and HRQoL using EuroQoL EQ-5D instrument. RESULTS: Bruxism was present in 29.7%
      of inmates. Results for EQ-5D (in brackets are data for the general population
      age and gender matched) were: EQ-index 1.3 (0.8), EQ-VAS 62 (80). Percentage
      reporting a problem for each dimension: Mobility (MO): 7.5 (9.6), Self Care (SC):
      6.1 (4.3), Usual Activities (UA): 17.9 (10.1), Pain/discomfort (PD): 43.9 (40.8),
      Anxiety/depression (AD): 54.6 (31.9). There was a strong correlation between
      bruxism and EQ-index, showing concordance and dependence and, as expected,
      discordance and dependence between bruxism and EQ-VAS. CONCLUSION: Bruxism
      prevalence is higher and HRQoL is worse in the prison population than in the
      general population; the presence of bruxism is correlated with lower HRQoL
      levels, and correlation is stronger for subjects at first prison experience and
      for higher education levels, thus suggesting higher effect of stress on these
      subjects.

PMID- 25055611
TI  - Oral health inequalities in Italian schoolchildren--a cross-sectional evaluation.
AB  - OBJECTIVE: To evaluate which of the following indicators of socio-economic status
      (SES) has the strongest association with dental caries status in a 6-year-old
      population: the educational level of each parent (individual-level); the mean
      price of housing/m2 in the area where the family resides; or the mean per capita
      income in the area where the family lives (area-level). MATERIAL AND METHODS:
      Dental caries was recorded in 2,040 schoolchildren (42.5% boys, 57.5% girls)
      using decayed/missed/filled surface index (d3 level) in primary dentition.
      Parents filled in a standardised questionnaire regarding nationality, level of
      education, frequency of dental check-up and perception of child's oral health and
      child's oral hygiene habits. RESULTS: At the individual-level of SES, mothers'
      educational level was associated with their children's caries severity (chi2(9) =
      147.51 p < 0.01): as educational level rose the proportion of children with high
      numbers of carious lesions fell. The two income indicators (area-level SES) were
      not associated. A multinomial logistic regression model was run for caries risk
      factors. Caries severity was used as dependent variable and the model was
      stratified by mothers' educational level. Mothers' perception of child's oral
      health was the only covariate that was always associated in every caries severity
      strata and for each level of mothers' education. CONCLUSIONS: The present study
      shows that mothers' educational level is a useful individual SES indicator for
      caries in Italian children living in a low-income population.

PMID- 25055612
TI  - Preparation, technology pay offwhen Middle East virus arrives in the heartland.

PMID- 25055613
TI  - Medicare ACO architect Gilfillan aims to transform care at CHE Trinity.

PMID- 25055614
TI  - System chiefs displace government officials at top of 50 most influential
      physician executives and leaders list.

PMID- 25055615
TI  - Hospitals eye docs for CEO roles as focus on quality and value grows.

PMID- 25055616
TI  - Promising but unproven. Hospitals face tough calls on acquiring pricey,
      experimental devices.

PMID- 25055617
TI  - Romneycare's results and the return of 'death panels'.

PMID- 25055618
TI  - Healthcare affordability is our obligation.

PMID- 25055619
TI  - Novant Health Forsyth rethinks feeding-tube use for dementia patients.

PMID- 25055620
TI  - Helping medical groups become high-performing systems of care.

PMID- 25055621
TI  - Surveillance of Charadriiformes in northern Australia shows species variations in
      exposure to avian influenza virus and suggests negligible virus prevalence.
AB  - The virologic surveillance of 4248 Charadriiformes since 1992 primarily from
      coastal northwest Australia did not detect any evidence of avian influenza virus
      (AIV) excretion (test prevalence = 0%; 95% confidence interval [CI]: 0%-0.09%).
      Past exposure to AIV was evident from serologic testing using nucleoprotein (NP)
      competitive-ELISA (c-ELISA) with an overall seroprevalence of 8.8% (95% CI: 8%
      9.7%). The c-ELISA seroprevalence of family Scolopacidae and genus Numenius was
      significantly higher when compared with other families and genera, respectively.
      Exposure risk profiles, based on c-ELISA seroprevalence, were compiled for 40
      species with the following species having significantly higher values when
      compared with the combined value of all other species: eastern curlew (Numenius
      madagascariensis), whimbrel (Numenius phaeopus), ruddy turnstone (Arenaria
      interpres), grey plover (Pluvialis squatarola), little curlew (Numenius minutus),
      red knot (Calidris canutus), sharp-tailed sandpiper (Calidris acuminata), and red
      necked stint (Calidris ruficollis). From hemagglutination inhibition (HI)
      testing, the more prevalent HI reactions were against H2, H5, H6, and H9
      subtypes, with no reactions against subtypes H11, H14, H15, and H16. Serologic
      testing using c-ELISA provided species risk profiles for optimizing a
      surveillance strategy for AIV in diverse populations of wild birds. The paucity
      of knowledge about the role of waders in the ecology of AIV and the overall very
      low to negligible virus prevalence reported globally, and in this study, suggests
      that waders are spillover hosts in shared ecosystems with a lesser role than
      previously considered.

PMID- 25055622
TI  - Retrospective study of turkey viral hepatitis in California turkey flocks, 2000
      2012.
AB  - Turkey viral hepatitis (TVH) is a disease characterized by an inflammation of the
      liver, and occasionally of the pancreas, of turkeys. Little is known about the
      occurrence of TVH in turkey flocks; thus, the aim of the present article is to
      summarize retrospectively 76 cases of TVH diagnosed at the California Animal
      Health and Food Safety System (CAHFS), University of California, Davis, in the
      years 2000 through 2012. Flocks diagnosed with TVH were between 7 and 61 days
      old, with an average age of 29.4 days and a median age of 28 days. In the
      majority of cases, increased mortality was reported. In 55 cases, gross lesions
      were present in the liver; the most common lesions were a few to numerous pale
      white foci in 35 cases. In livers of 74 cases, histologic lesions were observed.
      Multifocal necrosis with inflammation was observed in livers of 42 cases,
      inflammation but no necrosis in 22 cases, and necrosis without inflammation in 8
      cases. In 17 cases, pale white foci were found in the pancreas; in 4 cases,
      larger areas of the organ were pale. In 33 cases, histologic changes were
      observed in the pancreas. Necrosis with inflammation was observed in the pancreas
      of 17 cases, necrosis without inflammation in 7 cases, and inflammation without
      necrosis in 9 cases. No Salmonella was isolated from any of the livers cultured.
      Transmission electron microscopy of liver and pancreas demonstrated viral
      particles between 23 and 25 nm in two cases. Concurrent diseases were mostly
      poult enteritis (65 cases), but also respiratory diseases and colibacillosis. TVH
      occurred more often in turkeys during winter months. In conclusion, TVH was
      observedon a regular basis in California turkey flocks during the last 12 yr.

PMID- 25055623
TI  - S1 of distinct IBV population expressed from recombinant adenovirus confers
      protection against challenge.
AB  - Protective properties of three distinct infectious bronchitis virus (IBV) Ark
      Delmarva poultry industry (ArkDPI) S1 proteins encoded from replication-defective
      recombinant adenovirus vectors were investigated. Using a suboptimal dose of each
      recombinant virus, we demonstrated that IBV S1 amino acid sequences showing > or
      = 95.8% amino acid identity to the S1 of the challenge strain differed in their
      ability at conferring protection. Indeed, the S1 sequence of the IBV population
      previously designated C4 (AdIBVS1.C4), which protected the most poorly, differs
      from the S1 sequence of population C2 (AdIBVS1.C2), which provided the highest
      protection, only at amino acid position 56. The fact that a change in one amino
      acid in this region significantly altered the induction of a protective immune
      response against this protein provides evidence that the first portion of S1
      displays relevant immunoprotective epitopes. Use of an optimal dose of AdIBVS1.C2
      effectively protected chickens from clinical signs and significantly reduced
      viral load after IBV Ark virulent challenge. Moreover, increased numbers of both
      IgA and IgG IBV-specific antibody secreting lymphocytes were detected in the
      spleen after challenge. The increased response detected for both IgA and IgG
      lymphocytes after challenge might be explained by vaccine-induced B memory cells.
      The fact that a single vaccination with Ad/IBVS1.C2 provides protection against
      IBV challenge is promising, because Ad-vectored vaccines can be mass delivered by
      in ovo inoculation using automated in ovo injectors.

PMID- 25055624
TI  - A sensitive, reproducible, and economic real-time reverse transcription PCR
      detecting avian metapneumovirus subtypes A and B.
AB  - Use of real-time PCR is increasing in the diagnosis of infectious disease due to
      its sensitivity, specificity, and speed of detection. These characteristics make
      it particularly suited for the diagnosis of viral infections, like avian
      metapneumovirus (AMPV), for which effective control benefits from continuously
      updated knowledge of the epidemiological situation. Other real-time reverse
      transcription (RT)-PCRs have been published based on highly specific fluorescent
      dye-labeled probes, but they have high initial cost, complex validation, and a
      marked susceptibility to the genetic variability of their target sequence. With
      this in mind, we developed and validated a SYBR Green I-based quantitative RT-PCR
      for the detection of the two most prevalent AMPV subtypes (i.e., subtypes A and
      B). The assay demonstrated an analytical sensitivity comparable with that of a
      previously published real-time RT-PCR and the ability to detect RNA equivalent to
      approximately 0.5 infectious doses for both A and B subtypes. The high efficiency
      and linearity between viral titer and crossing point displayed for both subtypes
      make it suited for viral quantification. Optimization of reaction conditions and
      the implementation of melting curve analysis guaranteed the high specificity of
      the assay. The stable melting temperature difference between the two subtypes
      indicated the possibility of subtyping through melting temperature analysis.
      These characteristics make our assay a sensitive, specific, and rapid tool,
      enabling contemporaneous detection, quantification, and discrimination of AMPV
      subtype A and B.

PMID- 25055625
TI  - Ulcerative dermatitis and valvular endocarditis associated with Staphylococcus
      aureus in a hyacinth macaw (Anadorhynchus hyacinthinus).
AB  - An 18-yr-old male hyacinth macaw (Anadorhynchus hyacinthinus) was found dead in
      his aviary with no preexisting signs. The bird had a chronic history of feather
      damaging behavior, with severe ulcerative dermatitis. Pathologic findings
      revealed a vegetative valvular endocarditis, myocarditis, septicemia, chronic
      severe glomerulonephritis, and thyroid dysplasia. Staphylococcus aureus was
      isolated from the valve, the liver, and the skin. Repeated trauma and low-rate
      bacteriemia may have contributed to the development of endocarditis.
      Translocation of S. aureus skin infection in the bloodstream may lead to subacute
      endocarditis in humans and such mechanism is suspected in this case. This case
      suggests that endocarditis associated with S. aureus septicemia is a potential
      complication of feather damaging behavior. This case also reports a systemic
      complication of ulcerative dermatitis secondary to feather damaging behavior.
      Endocarditis has been poorly reported in psittacine species, and such medical
      complication of feather damaging behavior has never been reported to our
      knowledge. Furthermore, S. aureus is a bacteria of public health concern and
      should be integrated into the differential when pet parrots with dermatitis are
      in proximity to owners.

PMID- 25055626
TI  - Hematologic and plasma biochemistry reference intervals of healthy adult barn
      owls (Tyto alba).
AB  - Hematologic and plasma biochemistry parameters of barn owls (Tyto alba) were
      studied in collaboration by the Exotic Division of the Faculty of Veterinary
      Science of the Szent Istvan University and the Eotvos Lorand University, both in
      Budapest, Hungary. Blood samples were taken from a total of 42 adult barn owls
      kept in zoos and bird repatriation stations. The following quantitative and
      qualitative hematologic values were determined: packed cell volume, 46.2 +/- 4%;
      hemoglobin concentration, 107 +/- 15 g/L; red blood cell count, 3.2 +/- 0.4 x
      10(12)/L; white blood cell count, 13.7 +/- 2.7 x 10(9)/L; heterophils, 56.5 +/-
      11.5% (7.8 +/- 2 x 10(9)/L); lymphocytes, 40.3 +/- 10.9% (5.5 +/- 1.9 x 10(9)/L);
      monocytes, 1.8 +/- 2.1% (0.3 +/- 0.3 x 10(9)/ L); eosinophils, 1 +/- 1% (0.1 +/-
      0.1 x 10(9)/L); and basophils, 0.6 +/- 0.5% (0.1 +/- 0.1 x 10(9)/L). The
      following plasma biochemistry values also were determined: aspartate
      aminotransferase, 272 +/- 43 U/L; L-gamma-glutamyltransferase, 9.5 +/- 4.7 U/L;
      lipase, 31.7 +/- 11.1 U/L; creatine kinase, 2228 +/- 578 U/L; lactate
      dehydrogenase, 1702 +/- 475 U/L; alkaline phosphatase, 358 +/- 197 U/L; amylase,
      563 +/- 114 U/L; glutamate dehydrogenase, 7.5 +/- 2.5 U/L; total protein, 30.6 +/
      5.3 g/L; uric acid, 428 +/- 102 micromol/L; and bile acids, 43 +/- 18
      micromol/L. These results provide reliable reference values for the clinical
      interpretation of hematologic and plasma biochemistry results for the species.

PMID- 25055627
TI  - Detection and differentiation of CVI988 (Rispens vaccine) from other serotype 1
      Marek's disease viruses.
AB  - The serotype 1 Marek's disease virus (MDV) is the causative agent for Marek's
      disease (MD), a lymphoproliferative disease of chickens of great concern to the
      poultry industry. CVI988 (Rispens vaccine), an attenuated serotype 1 MDV, is
      currently the most efficacious commercially available vaccine for preventing MD.
      However, it is difficult to detect and differentiate CVI988 when other serotype 1
      MDVs are present. To facilitate the detection of CVI988, we developed two sets of
      primers for a mismatch amplification mutation assay (MAMA) PCR that targeted the
      single nulceotide polymorphism associated with the H19 epitope of the
      phosphorylated protein 38 gene. The PCR was very specific. One primer set
      (oncogenic primers) amplified DNA from 15 different serotype 1 MDVs except
      CVI988. The other primer set (CVI988 primers) amplified DNA from CVI988 but not
      from any of the other 15 serotype 1 MDVs. A real-time PCR assay was developed
      using MAMA primers, and specificity and sensitivity was evaluated in vitro and in
      vivo. Mixtures of plasmids (CVI988 plasmid and oncogenic plasmid) at various
      concentrations were used to evaluate the sensitivity/specificity of MAMA primers
      in vitro. Both primer setswere able to amplify as little as one copy of their
      respective plasmid. Oncogenic primers were highly specific and only amplified
      CVI988 plasmid when the concentration of oncogenic plasmid was very low (1 X
      10(1)) and CVI988 plasmid was very high (1 X 10(6)). Specificity of CVI988
      primers was not as high because they could amplify oncogenic plasmids when the
      concentration of CVI988 plasmid was 1 x 10(3) and the concentration of oncogenic
      1 x 10(2). Validation of MAMA primers in in vivo samples demonstrated that
      oncogenic primers can be used for both early diagnosis of MD in feather pulp (FP)
      samples collected at 3 wk of age and confirmation of MD diagnosis in tumors.
      CVI988 primers could be used to monitor CVI988 vaccination in samples with a low
      load of oncogenic MDV DNA (latently infected samples or negative) but not in
      samples with a high load of oncogenic MDV DNA (tumors). Our results suggest that
      monitoring CVI988 vaccination in FP samples collected at 1 wk of age ensures the
      specificity of the CVI988 primers.

PMID- 25055628
TI  - A chicken embryo lethality assay for pathogenic Enterococcus cecorum.
AB  - Pathogenic strains of Enterococcus cecorum cause outbreaks of arthritis and
      osteomyelitis in chickens worldwide. Enterococcal spondylitis (ES) is a specific
      manifestation of E. cecorum-associated disease of broilers and broiler breeders
      characterized by increased flock mortality, resulting from unresolved infection
      of the free thoracic vertebra by pathogenic E. cecorum. A study of 22 ES
      outbreaks in the southeast United States revealed that pathogenic E. cecorum
      strains isolated from spinal lesions were genetically clonal. Here, we compare
      the virulence of previously genotyped pathogenic strains (n = 8) isolated from
      spinal lesions and nonpathogenic strains (n = 9) isolated from ceca of unaffected
      birds in a chicken embryo lethality model. Strains were inoculated into the
      allantoic cavity of 12-day-old broiler and specific-pathogen-free (SPF) layer
      embryos; embryo survival was determined by candling eggs daily for 4 days.
      Significantly decreased survival occurred in both broiler and SPF embryos
      inoculated with pathogenic genotype strains compared with embryos inoculated with
      nonpathogenic genotype strains (broiler embryos, 23% vs. 60%; SPF embryos, 9% vs.
      61%). Embryos infected with pathogenic strains were unable to control infection
      and consistently showed gross changes typical of sepsis, including hemorrhage and
      edema. After 48 hr, similar changes were not observed in embryos infected with
      nonpathogenic strains. This embryo lethality assay provides a useful tool for
      understanding the genetic basis of E. cecorum virulence.

PMID- 25055629
TI  - Inactivation of infectious bursal disease and Newcastle disease viruses at
      temperatures below 0 C using chemical disinfectants.
AB  - This study evaluated the effectiveness of bleach, Surface Decontamination Foam
      (SDF), and Virkon in inactivating infectious bursal disease virus (IBDV) and
      Newcastle disease virus (NDV) at temperatures below 0 C. To simulate the
      influence of organic load on the effectiveness of disinfectants, as would be
      encountered in disinfecting farm vehicles and equipment, the viruses were
      suspended in preparations containing light or heavy levels of organic matter. A
      small volume of the viral suspension was applied to the upper surface of
      stainless steel carrier disks and these were then air dried. The dried virus
      inoculum was covered with disinfectant to which propylene glycol had been added
      to prevent freezing. The disks were incubated at various temperatures for periods
      up to 24 hr. With NDV, at -10 C all three disinfectants in both organic
      preparations achieved a 5 log 10 reduction within 5 min. Results with SDF were
      similar at -25 and -10 C. To achieve comparable reduction with Virkon and bleach
      at -25 C, contact periods up to 2 or 24 hr, respectively, were required. With
      IBDV, to achieve a 5 log 10 to reduction by treatment with Virkon or SDF at -20
      C, contact periods of 2 or 24 hr, respectively, were required in both organic
      preparations. It was concluded that at temperatures as low as -20 to -25 C, SDF
      was the most effective disinfectant for killing NDV and Virkon was most effective
      for killing IBDV. The finding that a contact period of up to 2 hr was required to
      kill IBDV, whereas NDV was killed within 5 min, attests to the greater stability
      of the former virus.

PMID- 25055630
TI  - West Nile virus and non-West Nile virus mortality and coinfection of American
      crows (Corvus brachyrhynchos) in California.
AB  - American crows are acutely sensitive to West Nile virus (WNV) infection, and crow
      mortality has been used in WNV surveillance to monitor enzootic transmission.
      However, non-WNV sources of mortality could reduce the reliability of crow death
      as a surveillance tool. Here, using a combination of histopathologic,
      toxicologic, virologic, and molecular techniques we describe causes of mortality
      in 67 American crows (Corvus brachyrhynchos) that were collected from a
      population in the Sacramento Valley of California in 2012 and 2013. Evidence of
      infectious disease was detected in 70% (47/67) of carcasses. The majority of
      deaths were linked to a suite of non-WNV viral, bacterial, and fungal infections
      (39%; 23/59 cases), WNV (36%; 24/67 cases), and an acute toxic event (25%; 15/59
      cases). Coinfections were detected in 20% (12/59) of birds and frequently were
      associated with WNV and poxviral dermatitis. Inferences about WNV activity based
      on crow mortality should be supported by laboratory confirmation because crow
      mortality frequently can be caused by other infectious diseases or toxic events.

PMID- 25055631
TI  - Marek's disease virus-induced transient cecal tonsil atrophy.
AB  - Marek's disease (MD) is a lymphoproliferative disease of domestic chickens that
      is caused by a highly cell-associated oncogenic alpha-herpesvirus, Marek's
      disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a
      latent infection within CD4+ T cells. MD is characterized by bursal and thymic
      atrophy and rapid onset of T cell lymphomas that infiltrate lymphoid tissues,
      visceral organs, and peripheral nerves with severe clinical symptoms that include
      transient paralysis, anemia, weight loss, and neurologic disorders. The cecal
      tonsils (CT) are considered the largest lymphoid aggregates of avian gut
      associated lymphoid tissue (GALT). Along with Peyer's patches, CT elicits
      protective immune responses against bacterial and viral pathogens in the
      intestinal tract of avian species. In this study we investigated the effect of
      MDV infection on CT structural changes and cytokine gene expression in two MD
      susceptible and resistant chicken lines. The histopathologic analysis revealed
      that MDV causes the loss of germinal follicular centers within the CT of the
      resistant line while inducing a severe, near-total lymphoid depletion in the
      susceptible line during cytolytic infection. The lymphoid depletion, however,
      recovered approximately 2 wk postinfection but the loss of germinal centers
      persisted during the latent phase of infection in both lines. The atrophy of this
      important GALT was transient and there were no visible differences between the CT
      of the infected and control birds of either line by 21 days postinfection. Of the
      genes tested, IFN-beta and IFN-gamma were up regulated in the CT of both infected
      lines during lytic infection. The expression levels of both genes were much
      higher in the susceptible line than in the resistant line. A similar pattern of
      expression was observed for IL-6, IL-10, IL-13, and iNOS. IL-12 was up regulated
      in the CT of birds of the susceptible line during all three phases of infection.
      An over expression of IL-18 was also observed in CT of the susceptible line
      during lytic and latent phases of infection. IL-8 was the only cytokine expressed
      at higher levels in the CT of the resistant line during the lytic and
      reactivation phases of infection. The histopathologic observations and gene
      expression profiling are further discussed.

PMID- 25055632
TI  - Susceptibility of avian pathogenic Escherichia coli from laying hens in Belgium
      to antibiotics and disinfectants and integron prevalence.
AB  - Avian pathogenic Escherichia coli (APEC) causes huge annual losses in the poultry
      industry worldwide. Multiresistance against antibiotics of APEC strains is
      increasingly seen in broilers, although much is still unknown about strains from
      laying hens where use of antibiotics is limited. Disinfection can reduce the
      infection burden. However, little is known about the presence of resistance
      against these products. Ninety-seven APEC strains were isolated from Belgian
      laying hens. The resistance to different classes of antibiotics was determined as
      well as the minimum inhibitory concentrations (MIC; agar and broth dilution) and
      minimum bactericidal concentrations (MBC) of five disinfectants most often used
      in the poultry industry (formaldehyde, glutaraldehyde, glyoxal, hydrogen
      peroxide, and a quaternary ammonium compound). The presence of integrons was
      determined by PCR Resistance to ampicillin (35.1%), nalidixic acid (38.1%),
      sulfonamides (SULFA, 41.2%), and tetracycline (TET, 53.6%) was high but
      resistance to other tested antibiotics was low. Nevertheless, two extended
      spectrum beta-lactamase producers were found. The MIC of the disinfectants for
      the APEC strains showed a Gaussian distribution, indicating that there was no
      acquired resistance. MBCs were similar to MICs via the broth dilution method,
      showing the bactericidal effect of the disinfectants. Twenty-one strains (21.6%)
      were found positive for class 1 integrons and a positive association between
      integron presence and resistance to trimethoprim, SULFA, and TET was found. No
      association could be found between integron presence and phylogenetic group
      affiliation. Susceptibility of APEC strains from laying hens to antibiotics is,
      in general, very high. Phenotypic resistance to commonly used disinfectants could
      not be found, indicating that the current use of disinfectants in the laying hen
      industry did not select for resistance.

PMID- 25055633
TI  - Immunoglobulin A as an early humoral responder after mucosal avian coronavirus
      vaccination.
AB  - Infectious bronchitis virus (IBV) is a highly contagious coronavirus prevalent in
      all countries with an extensive poultry industry and continues to cause economic
      losses. IBV strains of the Ark serotype are highly prevalent in the Southeastern
      United States despite extensive vaccination. One explanation for this observation
      is the high genetic variability of IBV. In addition, IBV Ark-type vaccines may
      induce suboptimal mucosal immune responses, contributing to the prevalence and
      persistence of the Ark serotype. To test this hypothesis, chickens were ocularly
      vaccinated with a commercially available live attenuated IBV Ark-Delmarva Poultry
      Industry vaccine strain and both mucosal and systemic antibody responses were
      measured. The highest immunoglobulin A (IgA) spot-forming cell (SFC) response was
      observed in the Harderian glands (HG) and to a lesser extent in the spleen and
      conjunctiva-associated lymphoid tissues, while a limited IgG SFC response was
      observed in either the mucosal or systemic immune compartment. Interestingly, the
      peak IgA SFC response occurred 2 days earlier in spleen than in the head
      associated lymphoid tissues despite ocular vaccination. Furthermore, IgA IBV
      specific antibody levels significantly increased over controls 3 days earlier in
      tears and 4 days earlier in plasma than did IgG antibodies. IgA antibody levels
      were higher than IgG antibody levels throughout the primary response in tears and
      were similar in magnitude in plasma. In addition, a very early increase in IgA
      antibodies on day 3 postvaccination was observed in tears; such a response was
      not observed in plasma. This early increase is consistent with a mucosal T
      independent IgA response to IBV. In the secondary response the IBV antibody
      levels significantly increased over controls starting on day 1 after boosting,
      and the IgG antibody levels were higher than the IgA antibody levels in both
      tears and plasma. In summary, ocular vaccination induced higher IgA antibodies in
      the primary IBV response, while the memory response is dominated by IgG
      antibodies. Thus, lower mucosal IgA antibody levels are observed upon secondary
      exposure to IBV, which may contribute to vulnerability of host epithelial cells
      to infection by IBV and persistence of the Ark serotype.

PMID- 25055634
TI  - Correlation between Marek's disease virus pathotype and replication.
AB  - Marek's disease (MD) virus (MDV) is an alphaherpesvirus that causes MD, a
      lymphoproliferative disease in chickens. Pathotyping has become an increasingly
      important assay for monitoring shifts in virulence of field strains; however, it
      is time-consuming and expensive, and alternatives are needed to provide fast
      answers in the face of current outbreaks. The purpose of this study was to
      determine whether differences in virus replication between pathotypes that have
      been reported using a small number of virulent (v) and very virulent plus (vv+)
      MDV strains could be confirmed with a large collection of MD viruses. Based on
      pilot study data, bursa, brain, and lung samples were collected at 9 and 11 days
      postinoculation (dpi) from birds challenged with 1 of 15 MDV strains. The
      correlation between virus replication and virulence was confirmed between vMDV
      strains and higher virulent strains, but in most cases, there was no significant
      difference between very virulent (vv) and vv+MDV groups. At both 9 and 11 dpi,
      chickens infected with vv and vv+MDV had significantly lower body weights and
      relative thymus and bursa weights compared with chickens challenged with vMDV.
      However, similar to virus quantity, there was no significant difference between
      weights in birds challenged with vv or vv+MDV. The significant differences
      observed in maternal antibody negative (ab-) chickens were not significant in
      maternal antibody positive (ab+) chickens, demonstrating the requirement of ab-
      birds for this type of comparison. These data do not support the use of virus
      replication or organ weights as an alternative to pathotyping for discrimination
      between all three virulent MDV pathotypes but may be useful for determining a
      virus replication threshold to choose which field strains meet a minimum
      virulence to be pathotyped by traditional methods.

PMID- 25055635
TI  - Genotyping, pathogenicity, and immunogenicity of Avibacterium paragallinarum
      serovar B-1 isolates from the Americas.
AB  - The bacterium Avibacterium paragallinarum is the etiologic agent of infectious
      coryza of chickens. Among the nine Kume serovars currently recognized in this
      bacterium, serovar B-1 is a common serovar in the Americas. In the current study,
      serovar B-1 isolates from Ecuador (seven isolates), Mexico (seven isolates) and
      Panama (two isolates) were genotyped. In addition one Panamanian, one Ecuadorian,
      and two Mexican isolates were used in a vaccination-challenge trial in which the
      vaccine was based on the 2671 serovar B-1 reference strain. Genotyping by
      enterobacterial repetitive intergenic consensus-based PCR (ERIC-PCR) resulted in
      ten distinguishable ERIC patterns for the 16 isolates and the two reference
      strains of Av. paragallinarum included in the study. No ERIC patterns were shared
      among isolates of the three different countries. In the vaccination-challenge
      trial, one isolate from Panama showed a significantly lower virulence than did
      the three other isolates. In terms of cross-protection, chickens vaccinated with
      reference strain 2671 and challenged with an Ecuadorian strain showed 40%
      protection, a significantly lower protection than the homologous protection
      level. The other three field isolates gave a similar protection level to the
      homologous challenge.

PMID- 25055636
TI  - A clinical survey of common avian infectious diseases in China.
AB  - Multiple common avian infectious diseases (CAIDs), namely, avian infectious
      diseases excluding highly pathogenic avian influenza and Newcastle disease, such
      as avian salmonellosis and coccidiosis, cause huge economic loss in poultry
      production and are of great significance in public health. However, they are
      usually not covered in the systems for reporting of animal diseases.
      Consequently, the distribution of CAIDs is not clear in many countries. Here, we
      report a clinical survey of CAIDs in China based on clinical diagnosis of eight
      veterinary clinics in 2011 and 2012. This survey provided the distribution data
      of viral, bacterial, and parasitic CAIDs in different types of avian flocks,
      seasons, and regions, data that are of great value in the research, prevention,
      and control of poultry diseases. This survey suggested that avian colibacillosis,
      infectious serositis in ducks caused by Riemerella anatipestifer, avian
      salmonellosis, fowl cholera, avian mycoplasmosis, avian aspergillosis,
      coccidiosis, low pathogenic avian influenza, infectious bronchitis, infectious
      bursal disease, and infectious laryngotracheitis are likely to be prevalent in
      the poultry in China.

PMID- 25055637
TI  - Campylobacter spp. and birds of prey.
AB  - A total of 170 birds of prey admitted to two Wildlife Rescue and Rehabilitation
      Centers of Italy were examined. Birds were divided by diurnal (n = 15) and
      nocturnal (n = 7) species, sampled by cloacal swabs, and examined for
      Campylobacter spp. by cultural and molecular methods. Campylobacter spp. were
      isolated in 43 out of the 170 (25.3%) birds of prey examined. Among these, 43/43
      (100%) were identified as Campylobacter jejuni and 10/43 (23.3%) were identified
      as Campylobacter coli recovered from mixed infections. Diurnal birds of prey
      showed a significantly higher prevalence value (P = 0.0006) for Campylobacter
      spp. than did nocturnal birds of prey.

PMID- 25055638
TI  - Seroprevalence of paramyxoviruses in synanthropic and semi-free-range birds.
AB  - Avian paramyxoviruses (APMVs) are classified into nine different serotypes (APMV
      1-9). Virulent strains of APMV-1 are already well characterized as the etiologic
      agent of Newcastle disease (ND), an important disease in poultry that is
      potentially capable of infecting all orders of avian species. However, very
      little is known about the other eight serotypes, the majority of which can cause
      disease in domestic birds. The role of synanthropic and semi-free-range birds as
      reservoirs of avian paramyxoviruses is not well understood and the main objective
      of this work was to evaluate the seroprevalence of APMV 1-9 in these kind of
      birds. A total of 296 sera, oropharyngeal swabs, and cloacal enemas were
      collected from semi-free-range birds belonging to four different species: feral
      pigeons (Columba livia var. domestica), hybrid ducks (Anas sp.), domestic geese
      (Anser anser domesticus), and white storks (Ciconia ciconia). Antibodies against
      NDV were found in 56.3% of domestic geese, 42.9% of feral pigeons, and 30.4% of
      hybrid ducks. Antibodies for other APMVs (-3, -4, -6, -7, -8, -9) were also
      found. Seven positive individuals were positive to real-time RT-PCR detection,
      all of them feral pigeons captured in 2006 and 2007. The results obtained
      reinforce the idea that semi-free-range birds may be good sentinels for the
      detection of NDV and other avian paramyxoviruses.

PMID- 25055639
TI  - Characterization and phylogenetic analysis of a highly pathogenic avian influenza
      H5N1 virus isolated from diseased ostriches (Struthio camelus) in the Kingdom of
      Saudi Arabia.
AB  - During 2007, two outbreaks of avian influenza virus (AIV) in backyard and
      commercial ostrich flocks were first reported in the Kingdom of Saudi Arabia
      (KSA). The infected ostriches suffered from depression, anorexia, and diarrhea
      and some exhibited sudden death. A rapid AIV-group antigen detection and real
      time reverse-transcription PCR (rtRT-PCR) were initially performed on cloacal and
      tracheal swabs collected from diseased birds. Pools from positive-tested swabs
      for each flock were utilized for virus isolation in specific-pathogen-free
      embryonating chicken eggs. H5N1 AIV was identified in the harvested allantoic
      fluids by hemagglutination followed by hemagglutination inhibition and rtRT-PCR.
      The viruses responsible for these two outbreaks were sequenced and characterized
      as HPAIV H5N1 (A/ostrich/Saudi Arabia/6732-3/2007 and A/ostrich/Saudi Arabia/3489
      73VIR08/ 2007) from backyard and commercial flocks, respectively. Phylogenetic
      analysis of both isolates revealed that the two viruses belong to clade 2.2
      sublineage II and cluster with the HPAIV H5N1 isolated from falcons and turkeys
      during 2007 in KSA.

PMID- 25055640
TI  - Investigating turkey enteric coronavirus circulating in the Southeastern United
      States and Arkansas during 2012 and 2013.
AB  - Periodic monitoring of poultry flocks in the United States via molecular
      diagnostic methods has revealed a number of potential enteric viral pathogens in
      continuous circulation in turkeys and chickens. Recently turkey integrators in
      the Southeastern United States and Arkansas experienced an outbreak of moderate
      to severe enteritis associated with turkey enteric coronavirus (TCoV), and
      numerous enteric samples collected from turkey flocks in these areas tested
      positive for TCoV via real-time reverse-transcriptase PCR (RRT-PCR). This report
      details the subsequent sequence and phylogenetic analysis of the TCoV spike
      glycoprotein and the comparison of outbreak-associated isolates to sequences in
      the public database. TCoVs investigated during the present outbreak grouped
      geographically based upon state of origin, and the RRT-PCR assay was a good
      indicator of subsequent seroconversion by TCoV-positive turkey flocks.

PMID- 25055641
TI  - Acute septicemia caused by Streptococcus gallolyticus subsp. pasteurianus in
      turkey poults.
AB  - Streptococcus gallolyticus, previously known as Streptococcus bovis biotypes I
      and II/2, is a well-known cause of sepsis and meningitis in humans and birds. The
      present case report describes an outbreak of fatal septicemia associated with S.
      gallolyticus subsp. pasteurianus (S. bovis biotype II/2) in 11 turkey flocks in
      Pennsylvania between 2010 and 2013. Affected poults were 2-3 wk of age. Major
      clinical observation was sudden increase in mortality among turkey poults without
      any premonitory clinical signs. Postmortem examination findings revealed acute
      septicemia with lesions such as fibrinous pericarditis, meningitis, splenic
      multifocal fibrinoid necrosis, hepatitis, osteochondritis, myositis, and
      airsacculitis. Gram-positive cocci were isolated from several organs by routine
      bacterial culture. Biotyping identified bacteria as streptococci, whereas 16S
      ribosomal RNA gene sequencing identified them as S. gallolyticus subsp.
      pasteurianus. Antibiotic susceptibility profiles revealed that all the strains
      isolated were sensitive to penicillin and erythromycin with different sensitivity
      profiles for other antibacterial agents tested. The present study reports the
      first confirmed case of acute septicemia in turkey poults caused by S.
      gallolyticus subsp. pasteurianus.

PMID- 25055643
TI  - Monoclonal hyperglobulinemia in lymphosarcoma in a cockatiel (Nymphicus
      hollandicus) and a blue and gold macaw (Ara ararauna).
AB  - A 15-yr-old cockatiel (Nymphicus hollandicus) presented with decreased activity
      and appetite. A presumptive diagnosis of lymphoproliferative disease was made
      because of a monoclonal band observed on plasma protein electrophoresis. The
      owner declined further diagnostics or treatment, and the bird died 2 yr later. In
      a second case, a 4-yr-old blue and gold macaw (Ara ararauna) presented with
      lethargy and anorexia. Despite supportive treatment, the bird died 7 days later.
      Blood studies also demonstrated a monoclonal band on plasma protein
      electrophoresis. The histologic review of tissues from both birds found extensive
      neoplastic lymphoplasmocytic cells in the liver and supported a diagnosis of
      lymphosarcoma.

PMID- 25055642
TI  - First isolation of Mycoplasma iowae in grey partridge flocks.
AB  - Mycoplasma iowae, an occasional pathogen of turkeys, was isolated for the first
      time from captive grey partridges (Perdix perdix). Clinical signs including
      respiratory and intestinal disorder were seen in birds of all ages but mainly in
      those kept housed during rearing. Mortality rates averaged over 20% during the
      year. Treatment with antibiotics and antiparasitic drugs produced only a
      transient improvement in condition. The gross pathology findings included poor
      body growth, lack of development of the breast muscles, abnormalities in the keel
      development, and bone fragility. Some birds showed infraorbital sinusitis with
      serous or fibrinous exudates and catarrhal tracheitis, while others presented
      serofibrinous airsacculitis and splenomegaly. Laboratory investigations revealed
      pure cultures of M. iowae in the gut as well as sinus and air sacs. While other
      organisms such as coccidia, Trichomonas, Escherichia coli, Clostridium
      perfringens, and Aspergillus spp. were detected, the similarity of the disease
      with that seen in turkeys infected with M. iowae strongly suggests that this
      mycoplasma may be the primary pathogen here. The presence of M. iowae in game
      birds commonly released into the wild could have serious implications
      particularly in areas where industrial poultry farms are concentrated.

PMID- 25055644
TI  - Amputation of polymelia in a layer chicken.
AB  - Polymelia was rarely recorded in birds; therefore, this report records the
      clinical and radiographic findings in a case of polymelia in a 7-mo-old layer
      Fayoumi chicken and the outcome of its amputation. The hen had two pericloacal
      extra limbs located caudal to the normal ones in an inverted position. The extra
      limbs were immovable and loosely attached to the underlying tissues. The
      supernumerary limbs had normal skin with ill-developed feathers. The extra limbs
      were fused proximally and crossed distally. Plain radiographic examination showed
      unequal numbers of bones and digits in both extra limbs. The right extra limb had
      a femur and tarsometatarsus while the left extra one had femur, tibiotarsus, and
      tarsometatarsus bones. The extra limbs appeared smaller than the normal ones and
      had neither muscles nor tendons. Amputation of the extra limbs under local
      infiltration analgesia was easy, safe, and curative.

PMID- 25055645
TI  - Fatal Ichthyocotylurus erraticus infestation in Inca terns (Larosterna inca) in a
      zoological collection.
AB  - In a breeding group of Inca terns (Larosterna inca), 14 birds died without
      antemortem signs of illness. Other than a poor body condition and a bloody
      cloaca, no symptoms were observed. Gross necropsy revealed severe segmental
      hemorrhagic enteritis with intralesional trematodes in most birds.
      Histopathologic examination revealed infiltration of lymphocytes, plasma cells,
      and granulocytes in the lamina propria of the duodenum and cross-sections of
      trematodes in the lumen. The parasites were identified as Ichthyocotylurus
      erraticus, a trematode of fish-eating birds. The cause of the infestation most
      likely was the feeding of unfrozen fresh fish. We describe the first case of a
      lethal I. erraticus infestation in Inca terns.

PMID- 25055646
TI  - An outbreak of blindness due to retinopathy in nine flocks of guinea fowl.
AB  - Blindness was observed in 10- to 14-day-old guinea fowl. The incidence ranged
      from 25% to 80% in nine flocks within a total population of 110,000 guinea fowls.
      Clinical signs of blindness in birds included aimless wandering, failure to find
      feed and water, lateral recumbency, loss of weight, and increased mortality. The
      birds lacked papillary reflexes to light, and there were no gross lesions in the
      eyes. Histologically there was degeneration and disorganization of photoreceptors
      in the retina. The guinea fowl came from three different breeder sources but all
      of the birds were given the same feed. The condition was not observed in the
      subsequent flocks that came from the same breeder sources but that were given
      different feed. Based on these observations, toxicity of an unknown ingredient in
      the feed is suspected as the cause of blindness in the guinea fowl.

PMID- 25055647
TI  - [Emission factors and PM chemical composition study of biomass burning in the
      Yangtze River Delta region].
AB  - The emission characteristics of five typical crops, including wheat straw, rice
      straw, oil rape straw, soybean straw and fuel wood, were investigated to explore
      the gas and particulates emission of typical biomass burning in Yangzi-River
      Delta area. The straws were tested both by burning in stove and by burning in the
      farm with a self-developed measurement system as open burning sources. Both gas
      and fine particle pollutants were measured in this study as well as the chemical
      composition of fine particles. The results showed that the average emission
      factors of CO, NO, and PM2,5 in open farm burning were 28.7 g.kg -1, 1.2 g.kg-1
      and 2.65 g kg-1 , respectively. Due to insufficient burning in the low oxygen
      level environment, the emission factors of stove burning were higher than those
      of open farm burning, which were 81.9 g kg-1, 2. 1 g.kg -1 and 8.5 gkg -1 ,
      respectively. Oil rape straw had the highest emission factors in all tested
      straws samples. Carbonaceous matter, including organic carbon(OC) and element
      carbon(EC) , was the foremost component of PM2, 5from biomass burning. The
      average mass fractions of OC and EC were (38.92 +/- 13.93)% and (5.66 +/-1.54)%
      by open farm burning and (26.37 +/- 10. 14)% and (18.97 +/- 10.76)% by stove
      burning. Water soluble ions such as Cl-and K+ had a large contribution. The
      average mass fractions of CI- and K+ were (13.27 +/-6. 82)% and (12.41 +/- 3.02)%
      by open farm burning, and were (16.25 +/- 9.34)% and (13.62 +/- 7.91)% by stove
      burning. The K +/OC values of particles from wheat straw, rice straw, oil rape
      straw and soybean straw by open farm burning were 0. 30, 0. 52, 0. 49 and 0. 15,
      respectively, which can be used to evaluate the influence on the regional air
      quality in YRD area from biomass burning and provide direct evidence for source
      apportionment.

PMID- 25055648
TI  - [Size distributions and source apportionment of soluble ions in aerosol in
      Nanjing].
AB  - To explore the seasonal variation and source apportionment of soluble ions in
      PM10, PM2.1 and PM1.1, the aerosol mass. concentration and soluble ion
      concentration were investigated during a one-year observation in the urban
      district and north suburb. As the results showed, (1)The concentrations of PM10,
      PM2.1, PM1.1 were in the order of winter > spring > autumn > summer. In spring,
      summer and autumn, the concentrations of PM10, PM2.1, PM1.1 in the north suburb
      were higher than in the urban, while the situation, was opposite in winter. (2)
      SO(2-)(4), NO(-)(3), Ca2+, NH(+)(4), Cl-, K+, Na+, F-, NO;, Mg2+ were measured,
      and their total concentration in PM10 was 46 microg.m -3 in urban sites and 39.6
      microg m in north suburbs. Mass fraction percentage o f water soluble ion in
      PM2.1-10, PM1 1-2.1, PM1.1 in the urban district increased from 20.4% to 49.5%
      and 56% , and the value in the north suburb increased from 18.3% to 37. 9% and
      42.5%. (3) Major ions, SO(2-)(4), NO(-)(3) , NH(+)(4) , second components and
      Ca2+ , had significant seasonal variation. In the urban district, the highest
      concentrations were observed in winter, and the lowest in summer, while in the.
      north suburb, the highest concentrations were observed in spring, and the lowest
      in summer. The seasonal changing climate in Nanjing and different anthropogenic
      influences with land surface in urban-suburb may be the major factors for the
      ions' seasonal variation. (4) NH(+)(4) , SO(2-)(4) , NO(-)(3) came from secondary
      chemical reactions of NH3, SO2, NO,, and these precursors mostly came from
      automobile exhaust in Summer while equally came from automobile exhaust and
      fossil fuel in winter. Cl- came from biomass burning in Winter . while
      transported from sea salt with Na+ in Summer. Ca2+ and Mg2+ came from ground dust
      and construction dust. K+, F- , NO(-)(2) may come from biomass burning and
      industrial emissions.

PMID- 25055649
TI  - [Characteristics of particulate matters and its chemical compositions during the
      dust episodes in Shanghai in spring, 2011].
AB  - A continuous air quality observation was conducted in the urban area of Shanghai
      from April 28 to May 18 in 2011. The mass concentration of particle matters and
      main chemical compositions of fine particle were measured and analyzed. The mass
      concentrations of PM10 and PM2.5 during the dust episode were much higher than
      those in non-dust episode, with the maximum daily mass concentrations of PM10 and
      PM2.5 reaching 787.2 microg.gm-3 and 139.5 microgm(-3) , respectively. The
      average PM2.5 /PM10 ratio was (32.9 +/-14. 6)% (15. 6% -85.1% ). The total water
      soluble inorganic ions(TWSII ) contributed (27.2 +/- 19. 2)% (4. 8% -80. 8% ) of
      total PM2.5, and the secondary water soluble ions (SNA) , including SO(2-)4 , NO
      (3) and NH(+)(4) , were (76.9 +/- 13.9)% (41.9%-94.2%) in TWSIl. The
      concentrations of TWSII and SNA in PM2.5 during dust days became lower than those
      in non-dust days while the trend of the ratio of Ca2+ to PM2.5, increased. The
      mean OC/EC value in non-dust days was higher than that in the heavy dust
      pollution episode, but lower than that in weak dust days. In addition, mineral
      rich particle in dust period had an acid-buffer effect, making particle alkaline
      in dust days stronger. In non-dust days, SO(2-)(4) and NO(-)(3) mainly existed in
      the form of NH4HSO4, (NH4)SO4, and NH4NO3, and combined with other mineral ions
      during dust days.

PMID- 25055650
TI  - [Numerical modeling analysis of secondary organic aerosol (SOA) combined with the
      ground-based measurements in the Pearl River Delta region].
AB  - Two simulations were conducted with different secondary organic aerosol (SOA)
      methods-VBS (volatile basis set) approach and SORGAM (secondary organic aerosol
      model) , which have been coupled in the WRF/Chem (weather research and
      forecasting model with chemistry) model. Ground-based observation data from 18th
      to 25th November 2008 were used to examine the model performance of SOA in the
      Pearl River Delta(PRD)region. The results showed that VBS approach could better
      reproduce the temporal variation and magnitude of SOA compared with SORGAM, and
      the mean absolute deviation and correlation coefficient between the observed and
      the simulated data using VBS approach were -4.88 microg m-3 and 0.91,
      respectively, while they were -5.32 microg.m-3 and 0. 18 with SORGAM. This is
      mainly because the VBS approach considers SOA precursors with a wider volatility
      range and the process of chemical aging in SOA formation. Spatiotemporal
      distribution of SOA in the PRD from the VBS simulation was also analyzed. The
      results indicated that the SOA has a significant diurnal variation, and the
      maximal SOA concentration occurred at noon and in the early afternoon. Because of
      the transport and the considerable spatial distribution of O3 , the SOA
      concentrations were different in different PRD cities, and the highest
      concentration of SOA was observed in the downwind area, including Zhongshan,
      Zhuhai and Jiangmen.

PMID- 25055651
TI  - [Observation of a photochemical event in Jiaxing during summer 2013].
AB  - To investigate the variation characteristics and causes of a high-level ozone
      pollution event during Aug. 5-11, 2013 in Jiaxing, the pollution gases (O3, NO2,
      NO, CO, SO2), atmospheric particles (PM10, PM2.5), and meteorological elements
      were observed in this study. The results indicated that the O3 concentration on
      the pollution days was 2. 4 times higher than that on normal days, with an
      exceeding rate of over 29.0% and up to 45. 8% on Aug. 9. This event was induced
      by the combined influences of intensive photochemical reaction at high
      temperature and in static stability weather condition with low humidity and wind
      speed. The diurnal variation of O3 showed a unimodal distribution on pollution
      and normal days, with the highest value at around 14:00. In the generation stage,
      the growth rates of O3 were 50.3 and 21.6 microg.(m3. h)-1 on pollution and
      normal days, respectively; in the extinction stage, the decrease rates of O3 were
      16.8 and 23.4 microg (m3.h)-1. The concentrations of NO, NO2, and CO on pollution
      days were 1. 1, 1.5, and 1.5 times higher than those on normal days, which
      provided favorable conditions for photochemical reaction. The concentrations of
      PM2.5, PM10, and the ratio of PM2.5 /PM10 on pollution days were 2.5, 2.3, and
      1.1 times higher than those on normal days, indicating that the photochemical
      reaction is more conducive to the formation of fine particles.

PMID- 25055652
TI  - [Spatial and temporal variations of near surface atmospheric CO2 with mobile
      measurements in fall and spring in Xiamen, China].
AB  - The study on the spatial distribution of near surface air pollutants carbon
      dioxide (CO2) and particulate matters (PM) is essential for understanding the
      pollution characteristics with mobile measurements. Near surface concentrations
      of CO2, PM and meteorological parameters were measured in Xiamen city, China
      along the route passing through different functional areas using the mobile
      laboratory during different time periods of the day [09:00- 12: 00, 13 :00- 16 :
      00, 22 : 00-01 : 00 (local time) ] in spring (April) and fall (November), 2013.
      Carbon dioxide, PM and meteorological parameters data were analyzed for the
      spatial distribution of CO2 in different functional areas and the relationship of
      CO2, and PM2.5. During the study period, the measurements started at the northern
      part of the city, across the suburban area and ended at about 60 km in the
      southern Xiamen. The spatial distribution of CO2 along the road showed a high CO2
      level in the central area of the city and low values in the outlying areas.
      Different CO2 concentrations were observed at different functional areas because
      of the differences in emissions from traffic and industry, the emission and
      absorption by vegetation, and meteorological conditions. The concentrations of
      CO, at different areas fell into the following order: areas with heavy traffic
      (477.33 micromol.mol-1 +/- 6. 11 micromol.mol-1 ) > commercial residential area
      (454. 95 micromol.mol-1 +/- 5.45 micromol.mol-1 ) > the naturalscenic spot
      (441.01 micromol.mol-1 +/- 6.24 micromol.mol-1 ) >cultivated land (436.79
      micromol.mol-1 +/- 1.87 micromol.mol-1 ) > mountain woodlands (434.06
      micromol.mol-1 +/-0.31 micromol.mol-1 ). The average CO, concentration in spring
      2013 was measured to be 452.04 micromol mol -1 +/- 20.24 micro.mol. mol-1 with
      the maximum value of 533.10 micromol.mol-1 at the heavy traffic area in downtown
      Jiahe on April 12, 2013 and the minimum value of 413.25 micromol.mol-1 on April
      10, 2013 at the mountain woodland, which is about 23 km away from the downtown
      area. The mountain woodland is surrounded by a reservoir and woods and regarded
      as the background area. The average CO2 concentration in fall 2013 was determined
      to be 451.80 micromol.mol-1 +/-21.56 micromol.mol-1 with the maximum value of
      526.45 micromol.mol-1 at a heavy traffic area of Xiahe road in downtown, on
      November 19, 2013 and the minimum value of 415.01 p.mol.mol-' at the mountain
      woodland on November 10, 2013. This phenomenon was called "CO2 dome" by Idso in
      1998. In addition, the CO2 concentrations tended to be the highest at night
      (22:00-01:00) and the lowest in afternoon (13:00-16:00). During overcast days,
      the CO, concentrations were generally higher than those on clear days. At
      different functional areas, differences between nighttime (22:00-01:00) and
      daytime (09:00-12:00 and 13:00-16:00) ranged from -0. 66-29.48 micromol.mol-1 in
      spring and from -4.01 micromol.mol-1-33.69 micromol.mol-1 in fall. The CO2
      concentrations at the urban and the suburban areas were also different in spring
      and autumn and at different time of the day. The CO2 concentration was in
      significant correlation with PM2.5 (R =0.73, P < 0. 01) indicating the important
      impact of traffic pollution on the ambient CO2 concentration.

PMID- 25055653
TI  - [Isotope compositions of elemental carbon in the smoke and ash from crop straw
      combustion].
AB  - Six genotypes of straws for rice, maize and wheat, respectively, were combusted
      under flaming and smoldering conditions, and the isotope compositions for
      elemental carbon ( EC) in the straw smoke and ash were investigated with an
      isotopic mass spectrometer. The results showed that the mean delta 13C values for
      EC in the flaming and smoldering smoke of rice straw were - 28. 3 per thousand
      and - 28.7 per thousand, with depletions of 2.7 per thousand and 3. 0 per
      thousand relative to that of total carbon (TC) in the straw, respectively. The
      mean delta 13C values for EC in the flaming and smoldering smoke of wheat straw
      were -28.5 per thousand and - 28. 0 per thousand, with a depletion of 0. 1 per
      thousand and enrichment of 0. 4 per thousand comparing to TC in the straw,
      respectively. The average values in two types of maize straw smoke were -17.2 per
      thousand and - 13. 6 per thousand,with a depletion of 3.4 per thousand and an
      enrichment of 0. 2 per thousand relative to TC in the straw, respectively. The
      mean delta 13C ratios for EC in the flaming and smoldering ash of rice straw were
      -27. 5 per thousand and -27. 3 per thousand, with depletions of 1.8 per thousand
      and 1. 6 per thousand comparing with TC in the straw, respectively. In the
      flaming and smoldering ash of wheat straw, the mean ratios were -27.4 per
      thousand and -26.0 per thousand, with enrichments of 0. 9 per thousand and 2. 4
      per thousand relative to TC in the straw, respectively. In the two types of ash
      for maize straw, the average delta13 C values for EC were - 15. 0 per thousand
      and - 14. 8 per thousand,which were 1. 2 per thousand and 1.0 per thousand
      lighter than those of the straw TC. In general, evident isotope fractionations
      occur between EC in both smoke and ash and TC in the corresponding straws,
      especially for rice and maize straws. The isotopic ratios may be useful in
      identifying and estimating the contribution of EC from straw combustion to
      ambient aerosol.

PMID- 25055654
TI  - [Development of a chemical ionization time-of-flight mass spectrometer for
      continuous measurements of atmospheric hydroxyl radical].
AB  - A home-made chemical ionization time-of-flight mass spectrometer (TOFMS) has been
      developed for continuous measurements of atmospheric hydroxyl radical. Based on
      the atmospheric pressure chemical ionization technique, an ionization source with
      orthogonal dual tube structure was adopted in the instrument, which minimized the
      interference between the reagent gas ionization and the titration reaction. A
      63Ni radioactive source was fixed inside one of the orthogonal tubes to generate
      reactant ion of NO(-)(3) from HNO3 vapor. Hydroxyl radical was first titrated by
      excess SO2 to form equivalent concentrations of H2SO4 in the other orthogonal
      tube, and then reacted with NO(-)(3) ions in the chemical ionization chamber,
      leading to HSO(-)(4) formation. The concentration of atmospheric hydroxyl radical
      can be directly calculated by measuring the intensities of the HSOj product ions
      and the NO(-)(3) reactant ions. The analytical capability of the instrument was
      demonstrated by measuring hydroxyl radical in laboratory air, and the
      concentration of the hydroxyl radical in the investigated air was calculated to
      be 1.6 x 106 molecules*cm ', based on 5 seconds integration. The results have
      shown that the instrument is competent for in situ continuous measurements of
      atmospheric trace radical.

PMID- 25055655
TI  - [Residual levels of acetochlor in source water and drinking water of China's
      major cities].
AB  - The concentration levels of acetochlor were investigated in source water and
      drinking water from 36 major cities in China by solid phase extraction (SPE)
      combined with gas chromatography - mass spectrometry (GC-MS). Acetochlor
      detection rate was 66.9% in all the 145 source water samples collected with an
      average concentration of 33.9 ng L-1. The average removal rate of acetochlor was
      limited through the drinking water treatment process. The detection concentration
      of the northeast region was the highest. The concentrations of acetochlor
      detected in lake were higher than those in river and groundwater as source water.
      The detection rate and concentration of Liaohe river watershed and the coastal
      watershed were the highest.

PMID- 25055656
TI  - [Vertical distribution of water quality and its influence on underwater light
      field in Lake Chaohu].
AB  - There are few reports on the vertical distribution of water quality and its
      influence on underwater light field. In our study, we analyzed the vertical
      distribution of water quality based on the in situ data in Lake Chaohu, and
      studied their influence on diffuse attenuation coefficients of downwelling
      irradiance Kd via Hydrolight simulation. It was indicated that the suspended
      matter and colored dissolved organic matter (CDOM) were relatively vertical
      uniform in Lake Chaohu; excluding algae scums at the surface, the vertical
      profiles of chlorophyll-a conformed to Gaussian distribution; the complex Kd in
      vertical was affected by chlorophyll-a and inorganic suspended matter. The
      analysis on vertical distributions of water quality and its influence on Kd could
      be the basis for further studying the influence of algae vertical heterogeneity
      on underwater light field in Case II waters.

PMID- 25055657
TI  - [Correlation between aquatic plant diversity and water environment in the typical
      sites of Hangzhou section of the Beijing-Hangzhou Grand Canal].
AB  - Community characteristics of aquatic plant are important indicators for water
      quality. In order to understand the distribution characteristics of aquatic
      plants in aquatic ecosystem of the Beijing-Hangzhou Grand Canal ( Hangzhou
      section) , and to analyze the relationship between water quality and plant
      community, an investigation of the aquatic plants in five typical sites was made
      in this study. Species composition, biological diversity, quantity distribution
      and dominant species of aquatic plants in five sites were studied for ecological
      changes. Physicochemical factors such as temperature, pH value, transparency,
      dissolved oxygen and main elements of living were also analyzed. Based on the
      results, the distribution of phytoplankton diversity and environment factor
      correlations by multivariate statistical analysis were discussed. The trophic
      levels of these sites were assessed by using related biological standards.
      Results indicated that the diversity of aquatic plant mainly depends on the
      diversity of phytoplankton in the typical sites of the Beijing-Hangzhou Grand
      Canal. We observed and identified 35 genus algae, including advantage community
      of Hyalodiscus Ehrenberg and Melosira Agardh, which belonged to Bacillariophyta.
      According to the impact on the phytoplankton diversity and distribution, factors
      such as dissolved oxygen, transparency, water temperature, etc. had an obvious
      influence on the distribution of phytoplankton in the existing 6 environmental
      factors, while the influence of pH value was the highest. In terms of water
      quality eutrophication, site Tangxi Bridge and Maiyu Bridge showed a relatively
      lighter pollution, while site Yiqiao Bridge, Gujia Bridge and Gongchen Bridge
      showed a higher pollution, and the pollution of site Yiqiao Bridge was the most
      serious.

PMID- 25055658
TI  - [Nitrogen and phosphate pollution characteristics and eutrophication evaluation
      for typical urban landscape waters in Hefei City].
AB  - To understand the water environment regimes of the city-circling water system in
      Hefei City, six typical landscape waters were chosen to investigate pollution
      characteristics of nitrogen and phosphate and evaluate water eutrophication level
      according to the monitoring data of water physicochemical characteristics and
      chlorophyll content from September 2012 to July 2013. Study results showed that
      (1) the six waters mentioned above have been seriously polluted by nitrogen and
      phosphorus loadings, with the monthly mean values of total nitrogen (TN) and
      total phosphorus (TP) concentrations far exceeding the universally accepted
      threshold values of water eutrophication; (2) the nitrogen contents in the waters
      of Nanfeihe River, Heichiba and Yuhuatang scenic spots exhibited a markedly
      monthly variation, and both TP and PO(3-)(4)-P in Nanfeihe River showed a
      fluctuated characteristic with high concentrations while presenting a significant
      upward trend in Yuhuatang scenic spot; (3) the average values of TN/TP ratios for
      Yuhuatang and Heichiba scenic spots were 104.7 and 158.3, respectively, and the
      ratios for Baohe Park, Yinhe Park, Xiaoyaojin Park, and city segment of Nanfeihe
      River were 16.8, 18.7, 6.4 and 16.8, respectively, indicating that the scenic
      waters of Yuhuatang and Heichiba were phosphate-limited whereas Xiaoyaojin Park
      was nitrogen-limited; (4) all the six scenic waters were, in general, subsumed
      under just two broad categories, namely Hechiba scenic spot and Nanfeihe River,
      which were seriously polluted, and clustered together, and the others fall into
      the second class; and (5) water eutrophication appraisal result indicated that
      the six waters were all in the state of eutrophication, and could be arranged in
      the order of eutrophication level, Yinhe Park > Heichiba scenic spot > city
      segment of Nanfeihe River > Xiaoyaojin Park > Yuhuatang scenic spot > Baohe Park.

PMID- 25055659
TI  - [Distribution of nitrogen and phosphorus in the sediments and estimation of the
      nutrients fluxes in Longjinghu Lake, Chongqing City, during the initial
      impoundment period].
AB  - Sediment cores from a newly formed urban lake (Longjinghu Lake in China's
      Chongqing City) were selected to study the vertical distribution characteristics
      of both nitrogen and phosphorus from the overlying water to porewater, and then
      fluxes of ammonia (NH4+ -N) and orthophosphate (PO(3-)(4)-P) from different areas
      of the lake were calculated using a one-dimensional transport-reaction model
      based on the Fick's First Law. The results showed that the mean ammonia
      concentrations in porewater of surface layers (0-5 cm) was 6. 13 mg-L-1 +/-3.07
      mg.L-1 , higher by a factor of 10 compared with that in the overlying water.
      While orthophosphate contents tended to increase downwards, reaching a peak in
      surface sediment porewater, and then decreased in downcore, with a mean
      concentration of 2. 01 mg.L-1 +/- 1.05 mg L-1. Based on the porewater diffusion
      model, ammonia were released from sediments to overlying water, which indicated
      potential internal nutrient releasing risk. Although the flux of ammonia in the
      "initial lake area" was higher than that in the "newly submerged area", the
      annual load contribution from the "newly submerged area" was 85% (3.95 t.a-1).
      Similar to ammonia, orthophosphate was also released from sediments to overlying
      water in the "initial lake area", with the highest fluxes in the former
      Longjinghu Lake and Longjingou Lake Reservoir, reaching 7. 89 mg. ( m2 d)-1 and
      6. 13 mg ( m2 .d)-1, respectively. However, in a portion of the "newly submerged
      area", orthophosphate in the overlying water was transported to the sediments,
      resulting in negative fluxes ranging from - 1.93 to -2.78 mg (m2 d) -1. The
      annual load of orthophosphate from the whole sediments was 0. 357 t.a-1, with 72%
      contributed by the "newly submerged area".

PMID- 25055660
TI  - [Pollution characteristics and health risk assessment of organochlorine
      pesticides (OCPs) in the water of Lake Qiandao and its major input rivers].
AB  - Organochlorine pesticides (OCPs) were quantitatively determined by GC in several
      surface water samples collected in July 2011 and November 2011 from Lake Qiandao
      (Xin'an River Reservoir) and its major input rivers. Then the component
      characteristics and source apportionment of HCHs and DDTs were confirmed, and the
      health risk assessment was evaluated. The results showed that 8 OCPs were found
      to be in trace amount, and p,p'-DDT, a-HCH and p,p'-DDE were the highest
      frequently detected OCPs. The concentrations of total OCPs in surface water of
      the studied Lake ranged from 1.9 to 7.6 ng-L-1 , which were at lower pollution
      level, and 1.2-212 ng.L-1 in the samples from its three major input rivers. The
      spatial distribution of OCPs in the water of lake was varying, and Xin'an River,
      the mainstream of the lake, was the main input source of OCPs. Also, different
      contamination patterns among sampling seasons were found, the concentrations of
      OCPs in surface water collected in wet period were higher than those in dry
      season, which display the characteristics of nonpoint source pollution. According
      to the ratio of feature components, the OCPs in surface water from the Lake
      Qiandao originated largely from long distance transmission or degradation of
      technical HCHs, while additional sources of DDTs existed in the region. In
      addition, human health risk assessment of ingestion through the drinking water
      and skin contact absorption was performed using EPA recommends methods, the
      carcinogenic and non-carcinogenic risks caused by OCPs were 0. 06 x 10(-7)-23. 2
      x 10(-7) and 3.43 x 10(-5) -6.01 x 10(-3), respectively. According to the
      acceptable risk level, the carcinogenic and non-carcinogenic risks of the
      chemicals investigated can be considered negligible in water body of Lake
      Qiandao.

PMID- 25055661
TI  - [Distribution of potential pathogenic bacteria in the Jiulong River Watershed].
AB  - Recently, the human activities including economic growth and urbanization posed
      serious environmental health risks to the Jiulong River Watershed (JRW). In order
      to gain a full understanding of the distribution of potential pathogenic bacteria
      (PPB) in this area, we used 16S rRNA amplicon pyrosequencing technology to
      investigate planktonic and benthic bacterial community in two main tributaries
      (North River, NR, and West River, WR) of the Jiulong River (JR). At the genus
      level, a total of 68 genera of PPB were identified in JR, which accounted for 6.
      1% of total gene sequences. Clostridium, Mycobacterium and Sphingomonas were
      three most dominant genera, which accounted for 54. 5% , 5.9% and 5. 6% of the
      total gene sequences respectively, and occurred in all samples. At the species
      level, a total of 48 species of PPB were identified in JR, which accounted for
      0.76% of total gene sequences. Afipia felis, Mycobacterium asiaticum, Clostridium
      baratii, Brucella melitensis and Delftia tsuruhatensis were the five most
      dominant species, and accounted for 48.9% , 20.3% , 8% , 2.7% and 1.7% ,
      respectively. Statistical analysis indicated that the number of taxa (species or
      genera) of PPB in JR water samples were significantly more than those from JR
      sediment samples. Moreover, WR water samples harbored the most abundant and
      diverse of PPB, suggesting that WR water might have a high potential risk for
      pathogen contamination. In addition, statistical analysis indicated that the
      diversity and abundance of PPB (species or genera) are significantly positively
      correlated with nutrient (nitrogen and phosphorus) concentrations, suggesting
      that human activities in the JRW such as sewage discharge from livestock and
      wastewater treatment facilities play important roles on affecting the
      distribution of PPB in JR. Therefore, in order to protect the public health, more
      efforts are needed to prevent water contamination, and conduct the real-time
      monitoring of PPB in JR.

PMID- 25055662
TI  - [Influence of the river-lake relation change on the distribution of heavy metal
      and ecological risk assessment in the surface sediment of Poyang Lake].
AB  - Effects of river (Yangtze River)-lake (Poyang Lake) relation on the distribution
      and potential ecological risk of Cu, Pb, Zn, Cr and Cd were investigated in
      surface sediment of Poyang Lake under different waterregimens. The results
      indicated: (1) the sediments of Poyang Lake were polluted by various
      concentrations of heavy metals mainly originated from particulates of Yangtze
      River, and Cu and Pb were the main pollution factors. The pollution level of
      determined heavy metals followed the order of Cu > Pb > Zn > Cr >Cd. The
      concentration ranges of Cu, Pb, Zn, Cr and Cd in the sediment of Poyang Lake were
      13.1-108.1 mg.kg-1 , 37-119.1 mg.kg-1, 29.9-129.9 mgkg-1, 13.3-98.6 mgkg-1 and 0.
      19-2.77 mg.kg-1 during the wet period, and 3.05-69.7 mg.kg-1, 27.5-105 mgkg-1,
      18.8-95.4 mg.kg-1, 7.34-70 mg.kg- and 0.033-0.406 mg.kg-1 during the dry period
      respectively. The region with the highest heavy metal concentrations was located
      in water input area of the " Five River" and water output area of " Hukou" ;
      (2)The regions with high risk of heavy metals in sediment were mainly located in
      the area of the trail of "Five Rivers" during the wet period; while during the
      dry period, the area with high risk of heavy metals in sediment enlarged, which
      was not only limited in the area of the trail of "Five Rivers", but also enlarged
      northwards. The potential ecological risk of "Hukou" was relatively high,
      however, the potential ecological risk of the sediment in the whole lake during
      the dry period was lower than that during the wet period. (3) With the change of
      river-lake relation, water level rose, the maintaining time was shortened during
      the wet period, the dry season appeared ahead of schedule, the transformation
      course of Poyang Lake from "Lake morphology" to " River morphology" increased,
      and the typical river properties were enhanced, which resulted in the decreased
      potential ecological risk of heavy metals in sediment of the whole lake, however,
      the area of high risk-region was enlarged northwards.

PMID- 25055663
TI  - [Spatiotemporal variation characteristics of heavy metals pollution in the water,
      soil and sediments environment of the Lean River-Poyang Lake Wetland].
AB  - Overlying water, sediments, surface soils in the typical wetland areas of Lean
      River and Poyang Lake which were rich in non-ferrous metal mineral resources on
      both sides of the river, were chosen for monitoring heavy metals including
      copper, lead and cadmium of base flow in average season, flood season, and dry
      season in 2012. Statistical analysis methods were coupled to characterize the
      spatiotemporal variation of heavy metals pollution and identify the main sources.
      The results indicated that the concentrations of copper were the highest in all
      samples of each sampling sites in the Lean River-Poyang Lake wetland. And the
      content values of copper, lead and cadmium in different samples of different
      sampling sites also showed that the content values of copper were higher than
      those of lead, and the content values of lead were also higher than those of
      cadmium. The results also showed that the heavy metals pollution of copper, lead
      and cadmium in flood season was the heaviest whereas the heavy metals pollution
      in dry season was comparatively light. The results of the contents of the three
      kinds of heavy metals elements in different sampling sites of the watersheds of
      lean River showed that the contents of copper in the samples from the upstream
      sampling sites of Lean River were higher than those of other samples from other
      sites. And the contents of lead in the samples from the downstream sampling sites
      of Lean River were higher than those of other samples from other sampling sites.
      The contents of cadmium in the samples from the midstream sampling sites of Lean
      River were higher than those of other samples from other sites. The first
      principal component representing copper pollution explained 36. 99% of the total
      variance of water quality. The second principal component concerning representing
      lead pollution explained 30. 12% of the total variance. The correlation analysis
      results showed that there were significant positive correlations among the
      contents of copper in sediments and the contents of copper in overlying water.
      And there was also significant positive correlation between the contents of
      copper in sediments and the contents of copper in the surface soils. And the
      correlation analysis showed that there were significant positive correlations
      among the contents of cadmium in sediments and the contents of cadmium in surface
      soils. The above results reflected that the copper pollution or cadmium sources
      of water, soil and sediments were consistent, which were mainly from heavy metal
      acidic waste of mining emissions. The correlations between other components were
      not very obvious, which reflected the sources of pollutants were different.

PMID- 25055664
TI  - [Dissolved organic matter (DOM) dynamics in karst aquifer systems].
AB  - Dissolved organic matter (DOM) and nutrients have a unique way of producing,
      decomposing and storing in southwest karst water systems. To understand the
      biogeochemical cycle of DOM in karst aquifer systems, we investigated the
      behavioral changes of DOM fluorescence components in Zhaidi karst river system.
      Two humic-like components (C1 and C2), and one autochthonous tyrosine-like
      component (C4) were identified using the parallel factor analysis (PARAFAC)
      model. Compared with the traditional physical and chemical indicators, spatial
      heterogeneity of DOM was more obvious, which can reflect the subtle changes in
      groundwater system. Traditional indicators mainly reflect the regional
      characteristics of karst river system, while DOM fluorescence components reflect
      the attribute gaps of sampling types.

PMID- 25055665
TI  - [Sensitivity analysis of AnnAGNPS model's hydrology and water quality parameters
      based on the perturbation analysis method].
AB  - Sensitivity analysis of hydrology and water quality parameters has a great
      significance for integrated model's construction and application. Based on
      AnnAGNPS model's mechanism, terrain, hydrology and meteorology, field management,
      soil and other four major categories of 31 parameters were selected for the
      sensitivity analysis in Zhongtian river watershed which is a typical small
      watershed of hilly region in the Taihu Lake, and then used the perturbation
      method to evaluate the sensitivity of the parameters to the model's simulation
      results. The results showed that: in the 11 terrain parameters, LS was sensitive
      to all the model results, RMN, RS and RVC were generally sensitive and less
      sensitive to the output of sediment but insensitive to the remaining results. For
      hydrometeorological parameters, CN was more sensitive to runoff and sediment and
      relatively sensitive for the rest results. In field management, fertilizer and
      vegetation parameters, CCC, CRM and RR were less sensitive to sediment and
      particulate pollutants, the six fertilizer parameters (FR, FD, FID, FOD, FIP,
      FOP) were particularly sensitive for nitrogen and phosphorus nutrients. For soil
      parameters, K is quite sensitive to all the results except the runoff, the four
      parameters of the soil's nitrogen and phosphorus ratio (SONR, SINR, SOPR, SIPR)
      were less sensitive to the corresponding results. The simulation and verification
      results of runoff in Zhongtian watershed show a good accuracy with the deviation
      less than 10% during 2005- 2010. Research results have a direct reference value
      on AnnAGNPS model's parameter selection and calibration adjustment. The runoff
      simulation results of the study area also proved that the sensitivity analysis
      was practicable to the parameter's adjustment and showed the adaptability to the
      hydrology simulation in the Taihu Lake basin's hilly region and provide reference
      for the model's promotion in China.

PMID- 25055666
TI  - [Movement characteristics of Cyanobacteria under stress of water-lifting
      aeration].
AB  - In order to study the impact of algae control mixing technology on the
      distribution characteristics and movement of Cyanobacteria, the floating and
      subsiding velocity of Cyanobacteria in Taihu Lake was measured under different
      conditions such as different illuminance, temperature and pressure. The
      Cyanobacteria showed strong propensity of floating under the illuminance from
      1500 1x to 6000 1x. The Cyanobacteria particle with floating velocity of more
      than 0.8 cm.min-1 accounted for 58% under the illuminance of 1 500 1x. The
      floating velocity slowed down when the illuminance was lower than 1 500 1x or
      higher than 6 000 1x. In the temperature range of 8 to 25 Celsius degree, the
      Cyanobacteria floated and the floating velocity increased with temperature. The
      Cyanobacteria floated under the pressure of 0- 0. 1 MPa and the floating velocity
      slowed down as the pressure increased. Most Cyanobacteria were suspended in the
      water when the pressure reached 0. 2-0. 3 MPa and only a small part of the
      Cyanobacteria floated or settled. When the pressure reached 0. 4-0. 6 MPa, the
      Cyanobacteria notably settled and the subsiding velocity increased with the
      increase of pressure. The Cyanobacteria particles with subsiding velocity of more
      than 1.0 cm.min-1 accounted for 52.5% when the pressure was 0. 6 MPa. Gas
      vesicles bursted when the gas vesicles of the Cyanobacteria could not bear the
      external pressure. The buoyancy of the Cyanobacteria diminished until the
      floating force became smaller than its weight, causing the particles of the
      Cyanobacteria to settle. Under normal atmospheric pressure, the particle diameter
      was positively correlated to the floating velocity, while negatively correlated
      to the density. Under high pressure, the particle diameter was positively
      correlated to the subsiding velocity and the density.

PMID- 25055667
TI  - [Influence of light wavelength and intensity on the reduction of divalent mercury
      in aquatic system].
AB  - Laboratory experiments were conducted to investigate the photo-reduction of
      HgCI2, under various light wavelengths and intensities. The whole process was
      tracked by changing Hg0 concentrations in argon and Hg0 flux was calculated for
      qualitative and quantitative analysis; the rate order was determined by both
      differential and integral methods. The principal results indicated: Higher
      mercury emission flux was observed under shorter light wavelength and stronger
      intensity, which shows the important role of photoenergy in the reaction. The
      degree of mercury reduction was determined by radiation wavelength and intensity,
      and it was also influenced by solution volume and the flow rate of carrier gas.
      Under different light conditions, Hg0 concentrations in argon all increased at
      the beginning and decreased after a specific time period, since the main
      reactions in rising period were the photo-reduction of Hg2+ and the emission of
      Hg0 while the reaction in decreasing period was the emission of Hg0 only. The
      rate order under visible light was the first order while it was the second order
      under UVA and UVB, which attributes to the fact that coordination complex has
      certain light absorption band, which is related with the available light
      wavelength provided by experimental lamps.

PMID- 25055668
TI  - [Dynamic effects of commonly co-existing anions on the removal of selenite from
      groundwater by nanoscale zero-valent iron].
AB  - Batch experiments are used to research selenite removal from groundwater by
      nanoscale zero-valent iron (nZVI) , and dynamic effects of commonly co-existing
      anions on the removal of selenite are also investigated. The results showed that
      under anoxic conditions,when nZVI dose was 0.1 g.L-1 , the concentration of Se(
      IV)/sodium chloride was 100 micromol.L-1/0. 01 mol L-1 , pH = 7.0, T = 25 degrees
      C +/- 1 degrees C, auto-adding 1 mmol.L -1 CO(2-)(3) or SO(2-)(4) , 5 mg. L -1
      humic acid (HA), the removals of Se( IV ) were obviously inhibited. The weak
      effect on the removal of Se( IV) was observed when added 0. 5 mmol L- Ca2+ or Mg2
      ,while concentrations of Ca2+ and Mg2+ were 3 mmol L-1 and 3 mmol L-1
      respectively, removal efficiency of Se( IV) were evidently decreased. Without
      coexisting ions, Se( IV) were totally removed in 20 min, while with co-existing
      ions, removal efficiency of Se( NV) were achieved 100% in 30 min. Bivalent iron
      tended to stationary with the remove of Se( WV) in reaction processes. ORP
      rapidly decreased from positive to negative in the process of reaction, which
      illustrated the process of remove Se( IV) by nZVI was the reduction reaction.

PMID- 25055669
TI  - [BiOBr promoted the photocatalytic degradation of beta-cypermethrin under visible
      light].
AB  - As a visible light photocatalyst, bismuth oxide bromide (BiOBr) was used to
      catalyze the degradation of beta-cypermethrin (beta-CP). The photocatalytic
      degradation of beta-CP was studied with gas chromatography. The effects of pH and
      catalyst dose on the photocatalytic degradation efficiency were discussed. The
      oxidization and mineralization of beta-CP were detected by chemical oxygen demand
      (COD) analyzer. The results showed that beta-CP could be effectively degraded
      under visible light irradiation using BiOBr as the catalyst. At given
      experimental conditions, the degradation rate of beta-CP reached 94. 68% after 10
      h and the COD removal rate reached 67. 99% after 36 h. With the increase of
      catalyst dose and pH value, the degradation rate was improved. The photocatalytic
      oxidation species was determined by peroxidase method and terephthalic acid
      fluorescence method. These results suggested that the photocatalytic degradation
      process mainly referred to hydroxyl radical ( OH) mechanism.

PMID- 25055670
TI  - [Adsorption of methylene blue from aqueous solution onto magnetic Fe3O4/ graphene
      oxide nanoparticles].
AB  - A simple ultrasound-assisted co-precipitation method was developed to prepare
      magnetic Fe3O4/graphene oxide (Fe3O4/ GO) nanoparticles. The characterization
      with transmission electron microscope (TEM) indicated that the products possessed
      small particle size. The hysteresis loop of the dried Fe3O4/GO nanoparticles
      demonstrated that the sample had typical features of superparamagnetic material.
      Batch adsorption studies were carried out to investigate the effects of the
      initial pH of the solution, the dosage of adsorbent, the contact time and
      temperature on the adsorption of methylene blue. The results indicated that the
      composites prepared could be used over a broad pH range (pH 6-9). The adsorption
      process was very fast within the first 25 min and the equilibrium was reached at
      180 min. The adsorption equilibrium and kinetics data fitted well with the
      Langmuir isotherm model and the pseudo-second-order kinetic model. The adsorption
      process was a spontaneous and endothermic process in nature. The composite
      exhibited fairly high adsorption capacity (196.5 mg.g-1) of methylene blue at 313
      K. In addition, the magnetic composite could be effectively and simply separated
      by using an external magnetic field, and then regenerated by hydrogen peroxide
      and recycled for further use. The results indicated that the adsorbent had a
      potential in the application of the dye wastewater treatment.

PMID- 25055671
TI  - [Selection of electrochemical anodic materials for PFOA degradation and its
      mechanism].
AB  - Perfluorooctanoate (PFOA) is environmentally stable and endocrine-disrupting. It
      was resistant to conventional biodegradation and advanced oxidation processes.
      Electrochemical oxidation method was adopted to degrade PFOA. The anodes,
      including BDD, Pt, Ti, Ti/RuO2, Ti/RuO2-IrO2, Ti/In2O3, Ti/SnO2-Sb2O5,-IrO2,
      Ti/SnO2-Sb2O5,-RhO2, Ti/SnO2-Sb2O5, Ti/ SnO2-Sb2O5,-CeO2 and Ti/SnO2-Sb2O5-Bi2O3,
      were selected as the candidate materials. The oxygen evolution potential (OEP)
      were determined by linear sweep voltammetry (LSV). The degradation ratios and the
      defluorination ratios were used to evaluate the oxidation ability of anodic
      materials. Ultrasonic electrochemical oxidation indirectly demonstrated that
      direct electron transfer was the initial step for PFOA decomposition. The anodes
      of Ti/SnO,-Sb20 ,-Bi2,03, Ti/SnO-Sb ,O,-CeO,, Ti/SnO2-Sb20, and BDD effectively
      degraded PFOA, and the decomposition ratios were 89. 8% , 89. 8% , 93. 3% and 98.
      0% , respectively. The removal ratios of PFOA on Ti/ SnO2-Sb2O5,-RhO2, Ti/SnO2
      Sb2O5-IrO2, and Ti/In2O3 anodes were low, and the values were 2. 1%, 2.3% , 12.
      5% and 3.1%, respectively. However, Ti, Ti/RuO2 and Ti/RuO2-IrO2, had no effect
      on PFOA. PFOA molecule transferred electrons to the anode, decarboxylated, and
      followed the CF2, unzipping cycle. The intermediate products detected were C6F13
      COO- , C5F11COO-, C4F9COO- and C3F7,COO-.

PMID- 25055672
TI  - [Occurrence and fate of typical antibiotics in a wastewater treatment plant in
      Southwest China].
AB  - The occurrence and fate of ten antibiotics were investigated in a municipal
      wastewater treatment plant in Southwest China. Antibiotics were identified and
      quantified using high performance liquid chromatography/tandem mass spectrometry
      after solid-phase extraction. The results showed that 10 antibiotics were present
      in wastewater, in concentrations ranging from ng L -1 to microg L-1. All of the
      target antibiotics were also detected in sludge with concentrations ranging from
      (0.92 +/-0.18) to (466.76 +/-77.46) ng.g-1, with azithromycin having the highest
      concentration (466.76 ng.g-1 dry weight). Mass balance analysis showed that
      biotransformation/ biodegradation was the main removal mechanism for the selected
      antibiotics, and sorption onto sludge was a relevant removal pathway for
      quinolone antibiotics, and azithromycin, which accounted for 9. 35% to 26. 96% of
      the initial loadings.

PMID- 25055673
TI  - [Effects and mechanism on removing organics and reduction of membrane fouling
      using granular macro-porous anion exchange resin in drinking water treatment].
AB  - A granular macro-porous anion exchange resin combined with coagulation was used
      as pretreatment of microfiltration membrane, and their effects and mechanism on
      removing organics and reduction of membrane fouling were evaluated. The results
      showed that resin could be effective in removing organics with medium and small
      molecular weight ( Mr) but ineffective in removing organics with large Mr, while
      couagulation could significantly remove organics with large Mr, with a limited
      removal for organics with medium and small Mr. Using resin alone as pretreatment
      could be effective in removal of organics but limited in reduction of membrane
      fouling. With combination of coagulation and resin as pretreatment of
      microfiltration, not only organics could be removed effectively, but also
      membrane fouling could be reduced.

PMID- 25055674
TI  - [Research on treatment of high salt wastewater by the graphite and activated
      carbon fiber composite electrodes].
AB  - High salinity wastewater is one of the difficulties in the field of wastewater
      treatment. As a new desalination technology, electrosorption technology has many
      advantages. This paper studied a new type of carbon-based electrodes, the
      graphite and activated carbon fiber composite electrodes. And the influencing
      factors of electrosorption and its desalination effect were investigated. The
      electrosorption device had optimal desalination effect when the voltage was 1. 6
      V, the retention time was 60 min and the plate spacing was 1 cm. The graphite and
      activated carbon fiber composite electrodes were used to treat the black liquor
      of refined cotton and sodium copper chlorophyll wastewater to investigate its
      desalination effect. When the electrodes were used to treat the black liquor of
      refined cotton after acid treatment, the removal rate of conductivity and COD
      reached 58. 8% and 75. 6% respectively when 8 pairs of electrodes were used. And
      when the electrode was used to treat the sodium copper chlorophyll wastewater,
      the removal rate of conductivity and COD reached higher than 50. 0% and 13. 5%
      respectively when 6-8 pairs of electrodes were used.

PMID- 25055675
TI  - [Preparation and application of the quinonyl chloromethylation polystyrene in
      biological treatment of wastewater].
AB  - The technology of non-water-soluble mediator anaerobic biological catalysis has
      attracted more and more attention in the field of environment technology. In this
      study, five kinds of quinonly compounds were grafted on the chloromethylation
      polystyrene macromolecular carrier by Friedel-Crafts reaction. Reaction factors
      of temperature and molar ratio for the 1,4-naphthoquinone grafting carrier were
      optimized, and the optimal temperature was 78 degreesC while the optimal molar
      ratio of 1, 4-naphthoquinone and chloromethylation polystyrene was 2: 1. Fourier
      infrared spectrum analysis confirmed that the quinone groups were successfully
      grafted on the macromolecular backbone chloromethylation polystyrene. Catalysis
      using the five kinds of quinonly materials as non-water-soluble redox mediators
      enhanced the biological denitrification rate and the decoloration of azo dyes,
      meanwhile these materials showed good reusability in the biodegradation of azo
      dye. This study developed a new method for the preparation of quinonly materials
      and revealed a new field in the technology of mediator catalysis.

PMID- 25055676
TI  - [Enhanced electro-catalytic oxidation of dye wastewater with FePMo12 adopted
      catalyst].
AB  - Electrochemical oxidation degradation of azo dyes has become a widely used method
      in recent years. Iron phosphomolybdate (FePMo12) was synthesized with
      molybdophosphoric acid and ferric salt. Morphology and microstructure of catalyst
      were chararerized by IR spectrometry and X-ray diffraction. The heteropolyanion
      showed a Keggin structure. Electrochemical oxidation of acid red 3R was
      investigated in the presence of FePMo12 supported on modified 4A molecular sieve
      (4A) as packing materials in the reactor. The results showed that the optimal
      technological conditions for decolorization of acid red 3R simulated wastewater
      were as follows: active component load 3% , electrolytic voltage 22 V, initial pH
      4, air-flow 0.08 m3 h- ', electrode span 3.0 cm. Under the opnrrizd conditions,
      the decolorization efficiency, COD and TOC removal efficiencies reached 75.3% ,
      65.4% and 46.0% after 90 min, respectively. With the addition of NaCI to the dyes
      solution during electrolysis, the decolorization efficiency increased, while the
      effect of Na2SO4 on the degradation was negative. The efficiency of degradation
      and mineralization of the acid red 3R were estimated based on the absorbance
      measurements by UV-vis. It shows that the conjugated structure of dye was
      destroyed primarily.

PMID- 25055677
TI  - [Formation and characterization of aerobic granules in a pilot-scale reactor for
      real wastewater treatment].
AB  - Microbial granules were successfully developed in a pilot-scale sequencing batch
      reactor (SBR) for the treatment of real municipal wastewater. The aerobic
      granules developed had good settleability with a settling velocity of > 21 mh-1.
      The mature granular sludge was capable of simultaneous removal of chemical oxygen
      demand (COD), nitrogen (N) and phosphorus (P). With the cycle of 3 h, the
      effluent COD, ammonium nitrogen (NH+4 -N) and total nitrogen (TN) concentrations
      were <50 mg L-1, <5. 0 mg L-1, and <15 mgL-1, respectively. The removal
      efficiency for TN and total phosphorus (TP) was about 50%. Examinations by
      confocallaser scanning microscopy (CLSM) showed that extracellular polymeric
      substances (EPS) were uniformly distributed throughout the granules, forming the
      granule structure matrix. X-ray diffraction (XRD) analysis indicated the presence
      of SiO2 and other metal oxides inside aerobic granules, implying that minerals in
      real wastewater might function as the seed in the initial stage of aerobic
      granulation.

PMID- 25055678
TI  - [Research on cultivation of aerobic granular sludge and its characteristics in
      sequencing fed batch reactor].
AB  - Aerobic granular sludge was cultivated in the sequencing fed batch reactor, and
      granules' characteristic and reactor's performance to the pollutants were
      studied. The SFBR was operated under the conditions as: inoculated with activated
      sludge former self-cultivated, fed with simulated wastewater, and continuous
      feed/intermittent discharge and alternately anaerobic/aerobic operation mode. The
      results showed that through gradually decreasing the settling time, aerobic
      granular sludge was successfully cultivated in 28 days, which was yellow,
      irregular shape, and small particle size (the average particle size was 0.56 mm).
      Under normal circumstances, the SVI stayed under 70 mLg-1. EPS (as MLVSS) reached
      the maximum 373.24 mg.g-1 on the 59 d, which increased about 2.5 times over the
      inoculums. However, EPS decreased sharply during the later period due to the
      disintegration of aerobic granular sludge. MLSS was always below 3 000 mg L -1
      during the middle and later periods in the reactor. During the 63 days'
      operation, the removal rate of COD by the reactor maintained at about 90% except
      the abnormal circumstances, and the effluent COD was less than 100 mg.L-1. TIN
      and ammonia nitrogen's removal efficiency by the reactor fluctuated greatly, and
      the removal rates were 44.45% -94. 72% and 43. 87% -93. 13% respectively. The
      removal rate of TP was between 44. 50% -97. 40% , which could remain above 60%
      under normal circumstances. Limited to the automatic control level, AGS was
      disadvantage in the competition with filamentous bacteria that overgrew easily
      during the long time aerobic starvation period at night, which eventually led to
      the collapse of AGS.

PMID- 25055679
TI  - [Effect of different volume loading of aerobic/anaerobic zone on nitrogen and
      phosphorus removal by biofilm and granular sludge coupling process].
AB  - The effect of different aerobic/anaerobic zone volume loading on nitrogen and
      phosphorus removal by biological film and granular coupling process was
      investigated using a self-designed Biofilm/Granular sludge coupling reactor.
      Three operating modes were conducted in the experiment. In operating mode I ,the
      volume of aerobic zone was 9. 66 L, and the volume of anaerobic zone was 15. 34
      L. In operating mode II , the volume of aerobic zone was 12. 56 L, and the volume
      of anaerobic zone was 12. 44 L. In operating mode III , the volume of aerobic
      zone was 15.42 L, and the volume of anaerobic zone was 9.58 L. Three operating
      modes expressed different volume loading of the reactor because of different
      aerobic/anaerobic zone. The results showed that the performance of ammonia
      nitrogen and phosphorus removal was a bit poor in operating mode I , the effluent
      nitrate nitrogen was higher in operating mode III compared with other modes,
      which brought the total nitrogen removal efficiency lower. The operating mode II
      was optimal for nitrogen and phosphorus removal. In operating mode II , the
      ammonia nitrogen removal efficiency was about 80. 63% , the volume loading rate
      of nitrogen removal was about 150. 27 g(m3 d)-1, and the COD removal efficiency
      was higher than 83.24%; the amounts of phosphorus release and uptake under
      anaerobic conditions were 7. 23 mg L-1 and 11. 93 mg L-1.

PMID- 25055680
TI  - [Adsorption of Cu2+ by xanthate-functionalized waste sludge].
AB  - Waste sludge from waste water treatment plants was treated with the carbon
      disulfide in alkaline medium to prepare xanth, aiming to explore an efficient way
      to recycle waste sludge. Fourier transform infrared spectroscopy (FTIR) was
      applied to characterize the sludge. Batch experiments were conducted to
      investigate the adsorption property of Cu2+ as well as effecting factors
      including pH and initial concentration of Cu2+ . Results show that the chemical
      modification introduces sulfur groups successfully and the adsorption capacity of
      xanthate-functionalized sludge increases by 20.6%- 46. 9% comparing to the
      pristine waste sludge. The Cu2+ removal efficiency of xanthate-functionalized
      sludge reaches 96.7% when the initial concentration of Cu2+ is 25 mgL-1. The
      adsorption process can attain equilibrium within 3 hours and kinetics is found to
      be best-fit the Pseudo-second-order equation. The process is jointly controlled
      by film diffusion and intraparticle diffusion. Both Langmuir model and Freundlich
      model can describe the adsorption, process well. The maximum adsorption capacity
      given by the Langmuir model is 142.92 mgg-1 at 25 degree C (pH = 5). Adsorption
      capacity increases with pH value (1-5) and initial Cu2+ concentration. The
      xanthate-functionalized sludge can be used as high performance adsorbents to
      recycle waste resources.

PMID- 25055681
TI  - [Mechanisms of copper uptake by submerged plant Hydrilla verticillata ( L. F. )
      royle and Myriophyllum spicatum L].
AB  - Cultivation experiments, including short-term copper uptake kinetics, uptake
      kinetics of Cu by different subcellular fractions and efflux of Cu, were carried
      out to investigate mechanisms of copper uptake by two species of submerged
      macrophyte, Hydrilla verticillata (L. f. ) Royle and Myriophyllum spicatum L. The
      results showed that: (1) Both H. verticillata and M. spicatum showed high influx
      rates for copper ions with no statistically significant differences [ Vmax (DW)
      is 2 micromol. (g min) - 1] ; (2) Both leaf and stem Cu concentrations of two
      strains of plants showed sharp increase with the external medium, and the
      equilibrium was reached for about 12 h after being exposed to solution with 2
      micromol L-1 Cu. Leaves of these two plants accumulated much higher
      concentrations of Cu than stems. Furthermore, Cu in leaves concentrated
      predominantly in cell walls ( > 60% ) , followed by soluble and organell
      fractions; (3) Copper accumulated in cell wall of H. verticillata leaf was
      considerably higher than that of M. spicatum, and Cu concentrated in
      intracellular fractions of leaves showed no statistically significant difference
      between these two plants. Moreover, ability of Cu accumulation and efflux by H.
      verticillata was higher than that by M. spicatum.

PMID- 25055682
TI  - [Properties of maize stalk biochar produced under different pyrolysis
      temperatures and its sorption capability to naphthalene].
AB  - Biochar was made from maize stalk under three different temperatures of 300, 500
      and 700 degreeC. The elemental composition of biochar was measured by elemental
      analyzer. Scanning electron microscope (SEM) was used to measure the surface
      morphology. Sorption of naphthalene to biochar was researched by batch sorption
      experiments. Results showed that, with the increase of temperature, C content
      increased from 66. 79% to 76. 30% , H and O contents decreased from 4.92% and 19.
      25% to 3. 18% and 9.53%, respectively; H/C, O/C, (O + N)/C, aromaticity and
      hydrophobicity increased, and polarity decreased. SEM results showed that maize
      stalk biochar was platy particles, and its roughness of surface increased with
      increasing temperature. The sorption of naphthalene on biochar followed the
      Lagergren pseudo-second order dynamic sorption model. Initial sorption rate and
      equilibrium sorption capacity increased as preparation temperatures increased at
      the same initial concentration of naphthalene. The isotherm sorption behavior can
      be described by the Freundlich model, which indicated that, as pyrolysis
      temperature increased, the sorption capacity of biochar increased, and
      nonlinearity increased first and then decreased. Biochar derived from maize stalk
      had distinct features when compared with other feedstocks, and its elemental
      composition, surface features and sorption behaviors were significantly
      influenced by pyrolysis temperature.

PMID- 25055683
TI  - [Beijing common green tree leaves' accumulation capacity for heavy metals].
AB  - Seasonal variation of heavy metal contents in leaves and their relationships with
      soil heavy metal pollution levels were studied through measuring and analyzing
      the leaves of the common tree species in Beijing and soil heavy metal contents,
      to detect heavy metal accumulation ability of plant leaves. The results showed
      that: (1) the contents of Cu, Pb, Zn in plant leaves first decreased and then
      increased, again declined with changing the seasons (from spring to winter). Cr
      concentration showed the trend of first increase and then decrease from spring to
      winter, and the highest in the autumn; the accumulation capacities of Cu for
      Babylonica and Japonica were higher in the spring, summer and autumn, while
      Tabuliformis was in winter; the higher accumulation capacities for Cr, Pb were
      Japonica and Platycladus, and in winter were Platycladus and Bungeana; the higher
      accumulation capacities for Zn were Babylonica and Bungeana, while Platycladus in
      winter; (2) the pollution degree of four kinds of heavy metals (Cu, Cr, Pb, Zn)
      from downtown to suburbs showed that: Jingshan (C =2.48, C is contamination
      factor) > Olympic (C = 1.27) > Songshan (C = 1.20) > Shuiguan (C = 1. 18); (3)
      the heavy metals concentration of same plant leaves in the water of the Great
      Wall changed larger, but those in the other three areas showed that: Jingshan >
      Olympic > Songshan; the ability of same species leaf to absorb different sorts of
      heavy metals showed that: Zn >Cu >Pb >Cr; the difference between Zn content and
      Cr content was significant (P <0.01); (4) the relationship between heavy metal
      content in plant leaves and soil heavy metal pollution levels presented a
      quadratic polynomial relation; the significant correlation was found between
      other three heavy metal contents of plant samples and soil samples, but they were
      not the case for the Cu, and the correlation coefficients were above 0. 9.

PMID- 25055684
TI  - [Assessment of heavy metal contamination by moss-bag method and road-dust method
      for Taizhou urban area].
AB  - The aims of this study were to examine the contents and distribution character of
      heavy metals in urban areas of Taizhou, Jiangsu Province. Contents of 8 kinds of
      metals, including As, Cd, Cr, Cu, Mn, Ph, V and Zn, in the moss-bags and road
      dusts were determined, and the method of potential ecological risk index was used
      to assess the heavy metal contamination. The results indicated that the current
      situation of heavy metal contamination was serious in Taizhou, and the ecological
      risks of heavy metals were high. The mean concentrations of Cd, Zn, Pb in the air
      near the ground were 8.41 , 6.94 and 5. 85 times higher than the soil background
      values, respectively; and the mean concentrations of Zn, Cd, Pb, and Cu in the
      road dusts were 22. 63, 6. 58, 5. 13 and 4. 45 times higher than the soil
      background values, respectively. The results of potential ecological risk index
      showed that Cd was the main ecological risk factor both in the air near the
      ground and the road soils, its contribution rates in ecological risks accounted
      for 92.43% in the air near the ground and 72. 46% in the road soils. The Pearson
      correlation coefficients of heavy metals showed that there was a significant
      correlation among the heavy metals in the air near the ground, which implied the
      sources of pollution in the air were fewer than those of the road dust. Analysis
      indicated that traffic emission was the major anthropogenic source and the key
      influencing factor for heavy metal contamination of Taizhou, and that the
      potential ecological risk of bus stations were the highest.

PMID- 25055685
TI  - [Effect of grazing on the temperature sensitivity of soil respiration in Hulunber
      meadow steppe].
AB  - Grazing is one of the major human activities which lead to disturbance on
      grassland ecosystem. Quantifying the effect of grazing on the temperature
      sensitivity of soil respiration ( Q10 ) is essential for accurate assessment of
      carbon budget in grassland ecosystem. This study was conducted on the grazing
      gradients experiment platform in Hulunber meadow steppe. Soil respiration was
      measured by a dynamic closed chamber method (equipped with Li 6400-09, Lincoln,
      NE, USA) during the growing season in 2011. The results showed that soil
      respiration had significant seasonal variation and the maximum occurred in July,
      which was mainly dominated by temperature. The order of average soil respiration
      during the period from May to September in different treatments was G1 > GO > G2
      > G3 > G4 > G5. Comparing with non-grazing treatment, Q10 under heavy grazing
      conditions (0. 92 Au hm-2) was reduced by about 10% , and was increased a little
      under light grazing conditions (0. 23 Au hm-2). There was a significant negative
      correlation between Q15 and grazing intensities (r = 0. 944, P <0. 05) . Grazing
      could decrease the temperature sensitivity of soil respiration to different
      degrees. The Q10 under different grazing gradients had positive linear regression
      relationships with aboveground biomass, belowground biomass, soil organic carbon
      and soil moisture. They could explain 71.0%-85.2% variations of Q10. It was
      suggested that the variation of Q10 was mainly determined by the change of biotic
      and environmental factors due to grazing.

PMID- 25055686
TI  - [Variation characteristic in soil respiration of apple orchard and its biotic and
      abiotic influencing factors].
AB  - To evaluate the orchard variability of soil respiration and the response of soil
      respiration to its influencing factors is helpful for a deep understanding about
      the effects of converting cropland to apple orchard. A field experiment was
      conducted in the Changwu State Key Agro-Ecological Station. Soil respiration,
      soil temperature, soil moisture and roots biomasses were periodically measured in
      a mature apple orchard during 2011 and 2012. Soil respiration decreased as the
      distance from the trunk increased. The cumulative soil respiration in the 0.5 m
      distance from the trunk was 20% and 31% higher than that in the 2 m-distance from
      the trunk, respectively in 2011 and 2012. The temperature sensitivity of soil
      respiration (Q10) was relatively lower in the 2 m-distance than that in the 0. 5
      m-distance in both years. Soil temperature and soil moisture were slightly higher
      in the 2 m-distance, but there was no significant difference between the 2 m
      distance and the 0. 5 m-distance. Soil respiration and soil temperature showed a
      significant exponential relationship, but there was no positive correlation
      between soil moisture and soil respiration. Soil temperature changes can explain
      seasonal variation of soil respiration well, but it could not explain its spatial
      variability. Root density was an important factor for the spatial variability of
      soil respiration and Q15. Variation of soil respiration coefficient was 23% -31%.
      Therefore, the distance from the trunk should be considered when estimating
      orchards soil respiration.

PMID- 25055687
TI  - [Influencing factors of mercury emission flux from forest soil at Tieshanping,
      Chongqing].
AB  - To study the effect of environmental influencing factors on soil mercury
      emissions, intact surface soil samples (0 to 5 cm) were collected from a Masson
      pine forest in Tieshanping, Choningng to conduct controlled experiments, and soil
      mercury emission flux was measured by dynamic flux chambers under different
      conditions. The results showed that the mercury emission significantly increased
      with the enhancement of solar radiation, air temperature, and soil water content.
      The mercury emissions in sunlight were 3 to 9 times higher than those in shade,
      but the latter condition should be more similar to the actual condition in the
      field. The mercury emission flux was significantly higher in summer than in
      spring and autumn, and was the lowest in winter. Higher in air temperature, soil
      water content had a stronger effect on soil mercury emission. Removal of
      litterfall significantly decreased soil mercury emission, mainly because the
      mercury content of litterfall was higher than that in mineral soil layer. In
      addition, soil mercury emission had an obvious trend of decay during a day,
      indicating that relatively low mercury content in forest soil might be a limiting
      factor of mercury emission. The mercury emission flux in the daytime measured in
      this study was( 14.3 +/- 19.6) ng. (m2 .h) -1 in summer, (3.50 +/-5. 36)ng- (m2
      h)-1 in spring and autumn, and (1.48 +/-3. 27)ng- (m2 h)-1 in winter. The steady
      state results above might therefore be overestimation of the actual emission in
      the field.

PMID- 25055688
TI  - [Characteristics of arsenic content in the livestock farms' surrounding
      environment in Shanghai suburbs].
AB  - In the suburbs of Shanghai, selected five large farms and surface water, feed,
      soil and vegetable samples were collected, and then total and inorganic arsenic
      were detected to survey the current arsenic level of the livestock farms in
      Shanghai suburban, as well as the usage situation of organic arsenic as feed
      additives. The results showed that the total arsenic content in water samples
      ranged from 0. 00 microgL-1 to 23.00 microg L-1 , below the first standard of
      surface water quality (50 microg L-1 ) ; total arsenic in feed was among 0.40
      12.13 mgkg-1 , in which inorganic arsenic was 10.0% -80.0% ; total arsenic in
      spot-checking feed samples was 0. 16-21.39 mg kg-1 and inorganic arsenic was 0.
      003-10. 67 mgkg-1 , and samples exceeding the limits of arsenic in feed accounted
      for 16. 7% ; total arsenic content in soils ranged from 8.08-18.50 mgkg-1 , in
      which 22. 2% samples were higher than the first standard of soil environmental
      quality, and inorganic arsenic accounted for 44. 2% -78. 9% of total arsenic;
      vegetables' total arsenic was 0. 003-0. 093 mg kg-1, not higher than the maximal
      residue limit of 0. 50 mg kg -1 on the current national standard; there were some
      differences in different parts of the same species vegetables on arsenic content:
      arsenic content in roots were higher than that in the aboveground part, and the
      bioconcentration factors showed a significantly positive correlation with the
      arsenic content in vegetables and a negative correlation with the arsenic content
      in rhizosphere.

PMID- 25055689
TI  - [Input and distribution of rice photosynthesized carbon in the tillering stage
      under different nitrogen application following continuous 13C labeling].
AB  - The input of rice-photosynthesized carbon (C) into soil plays an important role
      in soil C cycling. A 13C-labelled microcosm experiment was carried out to
      quantify the input of photosynthesized C into soil C pools in a rice-soil system
      during the tillering stage. Growing rice (Oryza sativa L. ) was continuously fed
      with 13C-labeled CO, ( C-CO, ) in a closed chamber without nitrogen (NO), or at
      different rates of N supply (N10,N20, N30, N40 or N60). The results showed that
      there were significant differences in rice shoot (1.58 g plot-1 to 4.35 g plot-1)
      and root (1.05 g plot-1 to 2.44 g plot-1 ) biomass among the N treatments after
      labeling for 18 days. The amounts of 13C in shoots and roots ranged from 44.0 g
      plot-1 to 157.6 g.plot-1 and 8.3 g.plot-1 to 49.4 g.plot-1, respectively, and
      generally followed the order of N60 > N40 > N20 > N10 > NO. The contents of rice
      planted 13C-SOC, 13C-DOC and 13C-MBC in soil carbon pool were much higher than
      those of CK (without rice and N supply). The amount of 13C-SOC ranged from 11.1 g
      plot - to 23.7 gplot-1 , depending on the rate of N addition, accounting for
      10.2% -18. 1% of the net assimilation. The amounts of 13C-DOC and 13C-MBC ranged
      from 4. 82-14.51 microg kg-1 and 526. 1-1 478.8 microg kg-1 , both depending on
      the N application rate. In addition, at 18-day of labeling, the 13C-SOC, 13C-DOC
      and 13C-MBC concentration was positively correlated with the rice biomass.
      Therefore, our results suggest that paddy soils can probably sequester more C
      from the atmosphere if more photosynthesized C enters the soils and N application
      can stimulate C rhizodeposition during the tillering stage.

PMID- 25055690
TI  - [Simulation study on the effect of salinity on the adsorption behavior of mercury
      in wastewater-irrigated area].
AB  - This study was designed to pinpoint the impact of salinity ( NaCl and Na2SO4,
      added at salinity levels of 0-5%, respectively) on the adsorption behavior of
      mercury in wastewater-irrigated areas of Tianjin City by batch and kinetic
      experiments. The results showed that, the Langmuir isotherm and the Elovich
      equation can well fitted batch and kinetic experimental data, respectively. As
      NaCI spiked in soil, Hg( II) adsorption capacity and strength had marked
      decreases, from 868.64 mgkg-1 and 1. 32 at control to 357.48 mgkg-1 and 0.63 at
      5% salinity level of NaCI, respectively. As Na2SO4 spiked in soil, Hg(II)
      adsorption capacity (parameter qm in Langmuir isotherm) and strength (parameter k
      in Langmuir isotherm) changed slightly, from 868.64 mg kg-1 and 1.32 at control
      to 739.44 mg.kg-1 and 1. 18 at 5% salinity level of Na2 SO4, respectively.
      Kinetic data showed that, Hg( II) adsorption rate (parameter b in Elovich
      equation) in soil was not influenced by Na2SO, addition. However, the addition of
      NaC1 had a great effect on mercury adsorption rate. Hg(II ) adsorption capacity
      as a function of CI- or SO(2-)(4) content in soil could be simulated by the
      natural logarithm model, while Hg( II ) adsorption rate as a function of CI-
      content in soil could be simulated by the linear model. The study manifested that
      NaCI can significantly increase migration of Hg( II ) in the soil irrigated with
      wastewater, which may enhance Hg( II) bioavailability in the soil and cause a
      hazard to surface water. Especially, it will be harmful to human body through the
      food chain.

PMID- 25055691
TI  - [Leaching behavior of Pb, Cd and Zn from soil stabilized by lime stabilized
      sludge].
AB  - Stabilization of Pb, Cd and Zn spiked soil by using lime-stabilized sewage
      sludge( LSS) as amendment was investigated in this study, and the effectiveness
      was evaluated by using leaching tests ( TCLP, SPLP and de-ionized water) and
      modified BCR sequential extraction procedure. The results of TCLP indicated that
      the concentrations of heavy metals in TCLP leachate reduced significantly with
      the increase of the mass percentage of the LSS and the leaching reduction rates
      were as high as 99. 54% for Zn, 99. 60% for Pb, 99. 85% for Cd at 40% of LSS
      addition. When evaluated by SPLP and de-ionized water leaching method, the
      concentrations of Zn and Pb in leachate decreased obviously at 10% and 20% of LSS
      additions, but subsequently increased at 30% and 40% because of redissolution of
      Zn and Pb at strong base condition. After pH value of LLS-stabilized soil was
      adjusted by ferrous sulfate and phosphoric acid for recovering soil plantation
      function, the pH value of the soil decreased effectively, in the meantime
      promoting the stabilization effectiveness of Pb and Zn. The BCR test revealed
      that compared with the spiked soil exchangeable proportion of Zn, Pb, Cd in the
      soil and the soils adjusted by ferrous sulfate obviously declined, which implied
      the migration for Pb, Cd and Zn of contaminated soil could be confined. This
      study results show that municipal LSS can be reused in the stabilization of heavy
      metal contaminated soils and physical and chemical properties of LLS-stabilized
      soil are improved for plantation.

PMID- 25055692
TI  - [Levels and distribution of short chain chlorinated paraffins in seafood from
      Dalian, China].
AB  - Seafood samples were collected from Dalian, China to study the accumulation and
      distribution characteristics of short chain chlorinated paraffins (SCCPs) by
      GC/ECNI-LRMS. Sum of SCCPs (dry weight) were in the range of 77-8 250 ng.g-1,
      with the lowest value in Scapharca subcrenata and highest concentration in
      Neptunea cumingi. The concentrations of sum of SCCPs (dry weight) in fish,
      shrimp/crab and shellfish were in the ranges of 100-3 510, 394-5 440, and 77-8
      250 ng.g-1 , respectively. Overall, the C10 and C11 homologues were the most
      predominant carbon groups of SCCPs in seafood from this area,and a relatively
      higher proportion of C12-13 was observed in seafood with higher concentrations of
      sum of SCCPs . With regard to chlorine content, Cl1,, CI8 and CI6 were the major
      groups. Significant correlations were found among concentrations of different
      SCCP homologues (except C1, vs. Cl10 ) , which indicated that they might share
      the same sources and/or have similar accumulation, migration and transformation
      processes.

PMID- 25055693
TI  - [Application of biotic ligand model for the acute toxicity of copper to Daphnia
      magna in water of Liaohe River and Taihu Lake].
AB  - The acute toxicity (48 h-LC50 ) of copper to Daphnia magna predicted by the
      biotic ligand model (BLM) was compared with the 48 h-LC50 measured in water
      samples from Liaohe River and Taihu Lake at four specific sites in wet and dry
      seasons. The results showed that 48 h-LC50 values predicted by BLM were 232.75
      411.49 microgL-1 and 48 h-LC50 values measured in the water samples were 134. 55
      350. 00 microg L-1 in three sites of Hongmiaozi of Liaohe River, Pingtaishan and
      Tuoshan of Taihu Lake, which had a better consistency. While for Tongjiangkou of
      Liaohe River, there was a difference between the BLM predictions and the measured
      values in wet and dry seasons. According to the predictions and the experimental
      results, water effect ratios (WERs) were in the range of 2. 18-5.79 and 1.88
      11.15 which all were higher than 1. The acute toxicity of Cu of all sites in dry
      season was greater than those in wet season, which might be that Cu complexation
      with dissolved organic matter (DOC) reduced the toxicity of Cu.

PMID- 25055694
TI  - [Phytotoxicity of copper oxide nanoparticles to metabolic activity in the roots
      of rice].
AB  - To study the toxicity of copper oxide nanoparticles (CuO NPs) on plant growth,
      the physiological and biochemical activities of rice (Oryza sativa L. ) seedlings
      were detected under different kinds of treatments (CuO NPs suspension, CuO BPs
      suspension and CuSO4 .5H2O solution), using distilled water (d H20) culture as
      contrast. The results showed that the response of rice roots to four treatments
      was very different. After treated with CuO NPs suspension, the rice roots were
      seriously damaged, the root activity obviously decreased, the MDA and H202
      content rose, and the activity of SOD and POD apparently increased. The effect of
      different treatments on rice roots followed the order of CuO NPs > CuSO4 .5H2O2 >
      CuO BPs > d H2O. The results demonstrated that CuO NPs had a serious effect on
      the root growth of rice, the toxicity of nanoparticles on rice root was not only
      caused by the release of Cu ion, the particles also played an important role, and
      that oxidative damage might be one of the main toxic mechanisms of copper oxide
      nanoparticles.

PMID- 25055695
TI  - [Enhancing effect of Tween 80 on degradation of triphenyltin by Bacillus
      thuringiensis].
AB  - So far, the information regarding enhanced degradation and biodegradation
      mechanisms of TPhT, an endocrine disruptor, is severely limited. Whether
      dearylation during TPhT degradation occurs successively or synchronously is not
      revealed clearly. To deal with these problems, this study focused on the
      biodegradation of TPhT and its metabolites by Bacillus thuringiensis through the
      acceleration of Tween 80. The results showed that Tween 80 obviously increased
      the TPhT solubility. After degradation by cells in the presence of 80 mg L-1
      Tween 80 for 2 d, the residual TPhT at 1 mg L-1 initially was decreased to 48.4%.
      During the biodegradation process, Tween 80 significantly reduced intracellular
      Na+, NH+4: and Mg2+ release, and increased extracellular Cl- , PO(3-)4 and K+
      utilization. Metabolites analysis revealed that phenyltin biodegradation
      initially proceeded by cleaving the aromatic ring, not by splitting the covalent
      bonds between the benzene rings and tin atom. Ring-cleavage reactions in the
      benzenes of TPhT occurred individually and synchronously, producing diphenyltin,
      monophenyltin and tin accordingly.

PMID- 25055696
TI  - [Long-term performance of microbial fuel cell using manure as substrate].
AB  - Long-term performance is of primary concern when considering the commercialized
      use of an microbial fuel cell(MFC). The long-term stability of MFC was studied
      using dairy manure as substrate over a testing time of 171 d. The results showed
      that the MFC could efficiently recover electricity from dairy manure during the
      long-time run, and the average power density was 6. 77 Wm-3 +/- 2. 11 W m-3. On
      day 70, the polarization curve was measured, the open circuit voltage, internal
      resistance and maximum power density of MFC were 0. 874 V, 22. 1 omega and 14. 1
      W.m -3, respectively. The 30-day TCOD removal decreased with increasing test
      time, and the CE during the 121-150 d period reached 17.5% +/-3.3%. Phylogenetic
      analyses revealed that the dominant microbial communities in anodic biofilm were
      Proteobacteria (45%) , Bacteroidetes (22%) , Firmicutes (17% ) and Actinobacteria
      (11% ). At genera level, the bacteria with electricity production and (or)
      cellulose degradation ability, such as Clostridium and Cellulomonas were the
      abundant taxa.

PMID- 25055697
TI  - [Influence of goethite on anaerobic fermentation of organic fraction of municipal
      solid waste (OFMSW)].
AB  - Effects of goethite on the anaerobic fermentation process of organic fraction of
      municipal solid wastes, including the biogas production and characteristics of
      leachate, were investigated in the anaerobic digesters constructed by PVC. The
      results showed that the addition of goethite promoted hydrolysis and acidogenesis
      efficiency of solid wastes and gas production rate. The total gas volume was
      163.4 L,which increased by 20% compared to the blank. The intermediate products
      of Fe2+ , NH+4 -N, NO-3 -N, COD and organic acids in the leachate were analyzed.
      Results showed that the addition of goethite reduced the system ORP to - 124 mV
      which could improve the activity of the anaerobic microorganism. Addition of
      goethite could also promote the utilization of organic acids which decreased the
      inhibition effects of organic acids on the anaerobic microorganism.

PMID- 25055698
TI  - [Pollutants produced in municipal refuse container during transfer process].
AB  - The generation and variation of the secondary pollutants in containers during
      seasons of a year were investigated in a municipal refuse transfer station of
      Shanghai. The results showed that the primary odors, the concentration of H2S was
      in a range of 0.3-10.3 mg.m-3, CH4 was in a range of 0.02% -2.97% and NH3 was in
      a range of 0.7-4.5 mg m-3, and their concentrations all reached the peak in the
      summer. The pH of the leachate was in a range of 5.4-6. 3, COD was 41 633-84 060
      mgL- 1, and BOD, was 18 116-34 130 mg.L , the concentration of pollutants were
      all higher in winter than that in summer. The ammonia concentration of leachate
      was in a range of 537-1222 mg.L'', while the TP fluctuated acutely in a range of
      17.98-296 mg L-1, exhibiting the relationship with seasonal variation. Extreme
      temperatures especially the high temperature in summer significantly affected air
      pollution producing, which indicated that containers should be kept against high
      temperature exposure and long residence time in order to prevent flammable gases
      and other pollutants generated largely.

PMID- 25055699
TI  - [Selective catalytic oxidation of H2S over supported Fe catalysts on CeO2
      intercalated laponite clay].
AB  - A series of Fe/CeO2-intercalated clay catalysts were synthesized successfully,
      the physicochemical properties of the catalysts were characterized by XRD, BET,
      XRF, TG, FT-IR, O2-TPD, H2-TPR and XPS methods. The catalytic performances for
      selective catalytic oxidation of H2S were further investigated, all catalysts
      exhibited high catalytic activities. Among them 5% Fe/Ce-Lap presented the best
      activity at 180 degreeC and the maximum sulfur yield was up to 96% due to the
      interaction between iron and cerium, which improved the redox ability of Fe3+ .
      Moreover, the strong oxygen adsorption capacity and the well dispersion of iron
      species improved the catalytic performance efficiently.

PMID- 25055700
TI  - [Preparation by different methods and characterization of desulfurization mixed
      oxides derived from hydrotalcites].
AB  - Hydrotalcite-based MgAl mixed oxides were synthesized by urea hydrolysis and
      constant-pH coprecipitation methods, and characterized by means of X-ray
      diffraction (XRD) , thermal gravity analysis-differential thermal gravity (TG
      DTG) , scanning electron microscope (SEM), N2-adsorption/desorption and CO2
      temperature programmed desorption (CO2-TPD), and their adsorption performances
      for SO2 were also tested. It was found that MgAl mixed oxides prepared by
      coprecipitation method would facilitate the catalyst to maintain a high specific
      area (148. 1 m2.g-1) and more basic sites, which resulted in higher SO2
      adsorption capacity and velocity. The SO2 adsorption capacity of the mixed oxides
      prepared by urea hydrolysis and constant-pH coprecipitation methods were 0.55 g.g
      1and 0. 79 gg-1 respectively at 700 degreeC.

PMID- 25055701
TI  - [Sampling methods for PM2.5 from stationary sources: a review].
AB  - The new China national ambient air quality standard has been published in 2012
      and will be implemented in 2016. To meet the requirements in this new standard,
      monitoring and controlling PM2,,5 emission from stationary sources are very
      important. However, so far there is no national standard method on sampling PM2.5
      from stationary sources. Different sampling methods for PM2.5 from stationary
      sources and relevant international standards were reviewed in this study. It
      includes the methods for PM2.5 sampling in flue gas and the methods for PM2.5
      sampling after dilution. Both advantages and disadvantages of these sampling
      methods were discussed. For environmental management, the method for PM2.5
      sampling in flue gas such as impactor and virtual impactor was suggested as a
      standard to determine filterable PM2.5. To evaluate environmental and health
      effects of PM2.5 from stationary sources, standard dilution method for sampling
      of total PM2.5 should be established.

PMID- 25055703
TI  - Introduction. Medical case histories as genre: new approaches.

PMID- 25055702
TI  - [A research overview of methanogens].
AB  - Methane is the second most important greenhouse gas in the atmosphere with a
      concentration (rate by volume) of 1.7 x 10(-6). Approximately 75% of methane in
      atmosphere comes from the activity of methanogens in the worldwide. The
      methanogens are anaerobic archaebacteria, according to 16S rRNA and other
      biochemical taxonomy. The methanogens can use compounds such as acetic acid,
      hydrogen and CO2 athylamine as substrates for methane production. The biochemical
      metabolisms of methanogens are greatly affected by natural environment where they
      live in. This paper will present a general situation of methanogens in term of
      history, morphology, taxonomy, metabolisms and ecology.

PMID- 25055704
TI  - The medical case narrative: distant reading of an epistemic genre.

PMID- 25055705
TI  - Telling cases: writing against genre in medicine and literature.

PMID- 25055706
TI  - K. P. Moritz's case poetics: aesthetic autonomy reconsidered.

PMID- 25055708
TI  - "Let me die in your house": cardiac distress and sympathy in nineteenth-century
      British medicine.

PMID- 25055707
TI  - Urban observation and sentiment in James Parkinson's Essay on the Shaking Palsy
      (1817).

PMID- 25055709
TI  - Representing chronic disorders of consciousness: the problem of voice in
      Allende's Paula.

PMID- 25055710
TI  - "If they smile he will flourish": mothers, doctors, and nineteenth-century
      children's literature.

PMID- 25055711
TI  - "The game is the double game": medical discourse in Tennessee Williams's the Loss
      of a Teardrop Diamond.

PMID- 25055712
TI  - "The intimate language of friendship with men": same-sex attraction in the Civil
      War fiction of S. Weir Mitchell.

PMID- 25055713
TI  - Descriptive analysis of longitudinal endoscopy for exercise-induced pulmonary
      haemorrhage in Thoroughbred racehorses training and racing at the Hong Kong
      Jockey Club.
AB  - REASONS FOR PERFORMING STUDY: Exercise-induced pulmonary haemorrhage (EIPH) is
      reported as a performance limiting condition in racehorses, yet few longitudinal
      studies characterising EIPH have been reported. OBJECTIVES: To characterise EIPH
      during training and racing in the absence of prophylactic medication with
      furosemide among horses imported to Hong Kong during 2007-2012. STUDY DESIGN:
      Retrospective descriptive study of clinical endoscopy, EIPH status, and racing
      records. METHODS: Thoroughbred geldings (n = 822) imported from New Zealand
      between 2007 and 2012 were retrospectively assigned to 4 groups: diagnosed with
      EIPH via endoscopy (EIPH+), graded using recognised criteria; observed with
      epistaxis (Epistaxis); free of EIPH on endoscopy (EIPH-); and those in which no
      endoscopy was performed. RESULTS: The majority of horses (89%) were subjected to
      endoscopy once or more (median 15, interquartile range 3-18). Of those undergoing
      endoscopy, 55% of horses were diagnosed EIPH+ which varied in severity. Few (4%)
      experienced epistaxis. EIPH+ was diagnosed most frequently (63%) after racing.
      There was no significant difference in the proportion of EIPH+ and EIPH- horses
      that raced. Racing career longevity was longest for EIPH+ horses. The number of
      starts in Hong Kong for EIPH+ horses was not significantly different to EIPH-
      horses. [Correction added on 9 January 2015, after first online publication: The
      term 'lifetime starts' has been changed to 'starts in Hong Kong' in the preceding
      sentence.] Days to retirement were longer for EIPH+ horses. Horses with mild
      EIPH+ (grade <3) were more likely to be retired for other causes whereas severe
      grades (>=3) were more likely to be retired for EIPH. CONCLUSIONS: Exercise
      induced pulmonary haemorrhage is common and varies in severity between
      individuals and between episodes in the same individual. There is no difference
      in racing career longevity between EIPH+ and EIPH- horses trained and raced
      without furosemide. See also correspondences by PS Morley and KW Hinchcliff; AD
      Richards; and S. Preston and C. M. Riggs.

PMID- 25055714
TI  - Tracing anthropogenic thallium in soil using stable isotope compositions.
AB  - Thallium stable isotope data are used in this study, for the first time, to
      apportion Tl contamination in soils. In the late 1970s, a cement plant near
      Lengerich, Germany, emitted cement kiln dust (CKD) with high Tl contents, due to
      cocombustion of Tl-enriched pyrite roasting waste. Locally contaminated soil
      profiles were obtained down to 1 m depth and the samples are in accord with a
      binary mixing relationship in a diagram of Tl isotope compositions (expressed as
      epsilon(205)Tl, the deviation of the (205)Tl/(203)Tl ratio of a sample from the
      NIST SRM 997 Tl isotope standard in parts per 10(4)) versus 1/[Tl]. The inferred
      mixing endmembers are the geogenic background, as defined by isotopically light
      soils at depth (epsilon(205)Tl ~ -4), and the Tl emissions, which produce Tl
      enriched topsoils with epsilon(205)Tl as high as +/-0. The latter interpretation
      is supported by analyses of the CKD, which is also characterized by
      epsilon(205)Tl ~ +/- 0, and the same epsilon(205)Tl value was found for a pyrite
      from the deposit that produced the cocombusted pyrite roasting waste. Additional
      measurements for samples from a locality in China, with outcrops of Tl sulfide
      mineralization and associated high natural Tl backgrounds, reveal significant
      isotope fractionation between soils (epsilon(205)Tl ~ +0.4) and locally grown
      green cabbage (epsilon(205)Tl between -2.5 and -5.4). This demonstrates that
      biological isotope fractionation cannot explain the isotopically heavy Tl in the
      Lengerich topsoils and the latter are therefore clearly due to anthropogenic Tl
      emissions from cement processing. Our results thus establish that isotopic data
      can reinforce receptor modeling for the toxic trace metal Tl. 

PMID- 25055715
TI  - Practice patterns in the management of patients with differentiated thyroid
      cancer in Ontario Canada 2000-2008.
AB  - BACKGROUND: The extent of treatment for differentiated thyroid cancer remains
      controversial. The objective of this study was to describe the variations in
      practice prior to diagnosis and for the first year after diagnosis, including the
      investigations, the extent of surgery and the use of RAI 131, for all patients
      with thyroid cancer (TC) treated Jan 1 2000 to Dec 2008 across Ontario Canada.
      METHOD: Population-based study of all patients who had a therapeutic surgical
      procedure for TC based on the data holdings of the Institute of Clinical
      Investigative Sciences (ICES) linking the Ontario Cancer Registry to the Ontario
      Health Insurance Plan and to the Canadian Institutes of Health Information. The
      analysis includes comparisons between health care utilization/geographic regions
      and between treating specialties. The study population was 12957 patients.
      RESULTS: There was a 112% increase in case detection over 9 years. Overall the
      initial (index) surgery was less-than-total thyroidectomy (LTT) in 37.6% and
      63.4% of the patients who had total thyroidectomy (TT) as an index surgery went
      on to adjuvant RAI, however there was wide variation in all aspects of patient
      care across the province, between Local Health Networks and between surgical
      specialties. CONCLUSION: In Ontario, there was wide variation for most aspects of
      the management of TC and, as the incidence of TC is increasing at least 7% per
      year in females, these data provide a foundation for future discussions, the
      provision of health care services and research.

PMID- 25055717
TI  - Observation "services" and observation "care"--one word can mean a world of
      difference.

PMID- 25055716
TI  - Assessing the impact of a school-based latrine cleaning and handwashing program
      on pupil absence in Nyanza Province, Kenya: a cluster-randomized trial.
AB  - OBJECTIVES: Improving school water, sanitation and hygiene (WASH) conditions
      reduces pupil absence and illness. However, these benefits may depend on the
      conditions of the latrines and availability of consumables. We sought to
      determine whether a low-cost, policy-relevant, environmental-level latrine
      cleaning intervention could improve latrine cleanliness, increase its use and
      reduce absenteeism. METHODS: In a three-arm, cluster-randomized trial we assessed
      absence via periodical roll-call among 17 564 pupils in 60 schools that had
      previously received WASH improvements as part of the SWASH+ project. Latrine
      conditions and use were also assessed using structured observation. Latrine
      cleanliness increased significantly during the post-intervention period among
      schools receiving the latrine cleaning package compared to controls, as did
      handwashing with soap. We found no difference in latrine use and absence across
      arms. CONCLUSIONS: The additive impact of cleaning may not have been strong
      enough to impact absence above and beyond reductions attributable to the original
      WASH infrastructure improvements and basic hygiene education the schools
      previously received. Improving latrine conditions is important for the dignity
      and well-being of pupils, and investments and strategies are necessary to ensure
      that school toilets are clean and pupil-friendly.

PMID- 25055718
TI  - Effects of atmospheric pollutants (CO, O3, SO2) on the allergenicity of Betula
      pendula, Ostrya carpinifolia, and Carpinus betulus pollen.
AB  - Pollen of Betula pendula, Ostrya carpinifolia, and Carpinus betulus was exposed
      in vitro to relatively low levels of the air pollutants, namely carbon monoxide,
      ozone, and sulfur dioxide. The allergenicity of the exposed pollen was compared
      with that of non-exposed pollen samples to assess if air pollution exposition
      affects the allergenicity potential of pollen. The immunodetection assays
      indicated higher IgE recognition by all sera of allergic patients to the pollen
      protein extracts in all exposed samples in comparison to the non-exposed samples.
      These results show that the pollen exposition to low pollutants' levels induces
      increased allergic reaction to sensitized individuals. 

PMID- 25055720
TI  - Paclitaxel-coated balloons in refractory nonanastomostic airway stenosis
      following lung transplantation.
AB  - Airway stenosis represents the commonest airway complication following lung
      transplantation, affecting between 7% and 18% of patients. Existing treatment
      options offer limited efficacy and can cause additional patient morbidity.
      Paclitaxel-coated balloons (PCB) have proved effective in managing
      postinterventional coronary artery re-stenosis. In a first-in-man study, we
      evaluated similar PCBs in refractory nonanastomotic airway stenosis in 12
      patients. Following a single application, luminal patency was maintained in 50%
      at 270 days. No significant peri-interventional or early postinterventional
      complications occurred. Given these encouraging initial findings, further studies
      appear warranted.

PMID- 25055719
TI  - Predicting health preference in chronic spinal cord injury.
AB  - CONTEXT/OBJECTIVE: Health preference values relate to a person's state of well
      being, and is a single metric anchored at 0 (death) and 1 (perfect health).
      Health preference plays a key role in health economics and health policy,
      particularly in interpreting the results of cost-effectiveness studies, and
      supports the allocation of healthcare resources. The current study used elements
      of the International Classification of Functioning, Disability and Health (ICF)
      framework to predict health preference in persons with spinal cord injury (SCI).
      METHODS: Data were collected by telephone survey on (1) demographics, (2)
      impairment (etiology, neurological level of injury, and ASIA impairment scale),
      (3) secondary health conditions (SHCs) using the SCI-Secondary Conditions Scale
      Modified, (4) functional abilities using the Spinal Cord Independence Measure
      (SCIM), and (5) health preference using the Health Utilities Index-Mark III (HUI
      Mark III) among adults with chronic SCI. Variables were categorized according to
      ICF headings and hierarchical regression analyses were used to predict HUI-Mark
      III scores. RESULTS: Adults with chronic traumatic or non-traumatic SCI (N = 357)
      reported a mean health preference score of 0.27 (+/-0.27). In predicting health
      preference, our model accounted for 55.1% of the variance with "body functions
      and structure", and "activity and participation", significantly contributing to
      the model (P < 0.0001). In particular, older age, being employed, and having
      higher SCIM scores were positively associated with health preference. Conversely,
      a higher SHC impact score was associated with poorer health preference.
      CONCLUSIONS: Variables representative of "activity and participation" largely
      influence health preference among persons with chronic SCI, which may be amenable
      to intervention. These findings could be applied to advocate for health promotion
      and employment support programs to maximize well-being in persons aging with
      chronic SCI in the community.

PMID- 25055721
TI  - Clinical and pathological correlates of severity classifications in trigger
      fingers based on computer-aided image analysis.
AB  - BACKGROUND: The treatment of trigger finger so far has heavily relied on
      clinicians' evaluations for the severity of patients' symptoms and the
      functionality of affected fingers. However, there is still a lack of pathological
      evidence supporting the criteria of clinical evaluations. This study's aim was to
      correlate clinical classification and pathological changes for trigger finger
      based on the tissue abnormality observed from microscopic images. METHODS: Tissue
      samples were acquired, and microscopic images were randomly selected and then
      graded by three pathologists and two physicians, respectively. Moreover, the
      acquired images were automatically analyzed to derive two quantitative
      parameters, the size ratio of the abnormal tissue region and the number ratio of
      the abnormal nuclei, which can reflect tissue abnormality caused by trigger
      finger. A self-developed image analysis system was used to avoid human
      subjectivity during the quantification process. Finally, correlations between the
      quantitative image parameters, pathological grading, and clinical severity
      classification were assessed. RESULTS: One-way ANOVA tests revealed significant
      correlations between the image quantification and pathological grading as well as
      between the image quantification and clinical severity classification. The
      Cohen's kappa coefficient test also depicted good consistency between
      pathological grading and clinical severity classification. CONCLUSIONS: The
      criteria of clinical classification were found to be highly associated with the
      pathological changes of affected tissues. The correlations serve as explicit
      evidence supporting clinicians in making a treatment strategy of trigger finger.
      In addition, our proposed computer-aided image analysis system was considered to
      be a promising and objective approach to determining trigger finger severity at
      the microscopic level.

PMID- 25055722
TI  - A national audit of maternity services in England.

PMID- 25055723
TI  - CO2-switchable multi-compartment micelles with segregated corona.
AB  - CO2-switchable multi-compartment micelles (MCMs) with a segregated corona formed
      by a purpose-designed ABC triblock copolymer are reported. They can be switched
      "on" and "off" when sequentially treated with CO2 and N2, due to the protonation
      deprotonation of the tertiary amine groups along the polymer skeleton. 

PMID- 25055724
TI  - Clinical significance of interleukin-22 in multiple myeloma.
AB  - OBJECTIVE: Interleukin-22 (IL-22) is a cytokine participating in many aspects of
      inflammation. Multiple myeloma (MM) is a malignant disease of plasma cells with
      characteristic immune deregulation. We estimated serum levels of IL-22 in MM
      patients, both in activity and remission, in order to apprehend its possible
      participation in MM biology. METHODS: We measured serum levels of IL-22 along
      with beta-2 microglobulin (B2M), paraprotein, and interleukin-1beta (IL-1beta),
      as well as degree of bone marrow infiltration, in 51 patients with active MM and
      in 22 of them in remission. RESULTS: We found that IL-22 was higher in active MM
      patients, compared to both controls and patients in remission, and also in
      patients in remission compared to controls. Moreover, IL-22 was increasing in
      parallel with the disease stage and also correlated with B2M, IL1-beta, and
      degree of infiltration. DISCUSSION: We suggest that the elevated levels of IL-22
      in active MM patients, in parallel with disease activity, and in positive
      correlation with IL-1beta, may represent the inflammatory element of the disease.
      This increased occurrence of IL-22 may enhance myeloma proliferation and growth,
      and moreover, may participate in the mechanisms of immune deregulation.

PMID- 25055725
TI  - The antioxidant system of sterlet seminal fluid in testes and Wolffian ducts.
AB  - Oxidative stress is a possible source of spermatozoa function deterioration.
      Seminal fluid (SF) protects spermatozoa against reactive oxygen species (ROS)
      attack during development in testes and transit through the reproductive tract.
      Spermatozoa curvilinear velocity and percent of motile cells as well as changes
      in thiobarbituric acid-reactive substance (TBARS) content, superoxide dismutase,
      and catalase activity, and uric acid concentration in SF were evaluated in
      sterlet sperm collected from testes 24 h after hormone induction of spermiation
      and from Wolffian ducts at 12, 24, 36, and 60 h after hormone injection (HI).
      While testicular spermatozoa motility was not initiated in activating medium,
      Wolffian duct sperm showed low motility at 12 h, significant increase at 24 and
      36 h, and decrease at 60 h. Testicular SF was characterized by the highest level
      of TBARS and activity of studied enzymes compared with SF from Wolffian duct
      sperm at 24 h post-HI. In fluid from Wolffian duct sperm, a significant increase
      in TBARS content was shown at 36-60 h post-HI. In contrast to testicular SF, in
      SF from Wolffian duct sperm, this increase was not counterbalanced by changes in
      the studied variables of antioxidant system. This may be the source of the
      observed decrease in spermatozoa motility parameters 60 h post-HI. The results
      may confirm a dual role of ROS in fish sperm physiology. The data with respect to
      decrease in sturgeon spermatozoa motility parameters at 60 h post-HI should be
      taken into account in artificial sturgeon propagation.

PMID- 25055726
TI  - Characterization and ontogenetic development of digestive enzymes in Pacific
      bluefin tuna Thunnus orientalis larvae.
AB  - The major digestive enzymes in Pacific bluefin tuna Thunnus orientalis larvae
      were characterized, and the physiological characteristics of the enzymes during
      early ontogeny were clarified using biochemical and molecular approaches. The
      maximum activity of trypsin (Try), chymotrypsin (Ct) and amylase (Amy) was
      observed at pH 6-11, 8-11 and 6-9, respectively. Maximum activity of Try, Ct and
      Amy occurred at 50  degrees C, that of lipase (Lip) was at 60  degrees C and that
      of pepsin (Pep) was at 40-50  degrees C. These pH and thermal profiles were
      similar to those for other fish species but differed from those previously
      reported for adult bluefin tuna. Enzyme activity for all enzymes assayed was
      found to decrease at high temperatures (Try, Ct, Amy and Pep: 50  degrees C; Lip:
      40  degrees C), which is similar to findings for other fish species with one
      marked exception-increased Try activity was observed at 40  degrees C. Lip
      activity appeared to be dependent on bile salts under our assay conditions,
      resulting in a significant increase in activity in the presence of bile salts.
      Ontogenetic changes in pancreatic digestive enzymes showed similar gene
      expression patterns to those of other fish species, whereas marked temporal
      increases in enzyme activities were observed at 10-12 days post hatching (dph),
      coinciding with previously reported timing of the development of the pyloric
      caeca in bluefin tuna larvae. However, complete development of digestive function
      was indicated by the high pep gene expression from 19 dph, which contradicts the
      profile of Pep activity and previously reported development timing of the gastric
      gland. These findings contribute to the general knowledge of bluefin tuna larval
      digestive system development.

PMID- 25055727
TI  - Self-enhanced catalytic activities of functionalized graphene sheets in the
      combustion of nitromethane: molecular dynamic simulations by molecular reactive
      force field.
AB  - Functionalized graphene sheet (FGS) is a promising additive that enhances
      fuel/propellant combustion, and the determination of its mechanism has attracted
      much interest. In the present study, a series of molecular dynamic simulations
      based on a reactive force field (ReaxFF) are performed to explore the catalytic
      activity (CA) of FGS in the thermal decay of nitromethane (NM, CH3NO2). FGSs and
      pristine graphene sheets (GSs) are oxidized in hot NM liquid to increase their
      functionalities and subsequently show self-enhanced CAs during the decay. The CAs
      result from the interatomic exchanges between the functional groups on the sheets
      and the NM liquid, i.e., mainly between H and O atoms. CA is dependent on the
      density of NM, functionalities of sheets, and temperature. The GSs and FGSs that
      originally exhibit different functionalities tend to possess similar
      functionalities and consequently similar CAs as temperature increases. Other
      carbon materials and their oxides can accelerate combustion of other
      fuels/propellants similar to NM, provided that they can be dispersed and their
      key reaction steps in combustion are similar to NM. 

PMID- 25055728
TI  - A prospective study of the association of patient expectations with changes in
      health-related quality of life outcomes, following total joint replacement.
AB  - BACKGROUND: Patient expectations regarding surgery may be related to outcomes in
      total joint replacement (TJR). The aim of this study was to determine the
      association of patient expectations with health related quality of life (HRQoL)
      outcomes measured by Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) and Short Form 12 (SF-12) and satisfaction with current symptoms
      measured on a 4-point Likert scale, one year after surgery, adjusting for Body
      Mass Index (BMI), age, gender, joint, education, previous intervention and
      baseline scores. METHODS: Consecutive patients preparing for TJR of the knee or
      hip due to primary osteoarthritis (OA) in 15 hospitals in Spain were recruited
      for the study. Patients completed questionnaires before surgery and 12 months
      afterwards: five questions about expectations before surgery; an item to measure
      satisfaction; two HRQoL instruments-WOMAC and SF-12; as well as questions about
      sociodemographic information. To determine the association of patient
      expectations at baseline, with changes in HRQoL 12 months after surgery and with
      satisfaction, general linear models and logistic regression analysis were
      performed. RESULTS: A total of 892 patients took part in the study. Patients who
      had higher pain relief or ability to walk expectations improved more in HRQoL at
      12 months. Moreover, patients with high daily activity expectations were more
      satisfied. CONCLUSIONS: Patients with higher baseline expectations for TJR,
      improved more in HRQoL at one year and had more likelihood to be satisfied than
      patients with lower expectations, adjusted for BMI, age, gender, joint,
      education, previous intervention and HRQoL baseline scores.

PMID- 25055729
TI  - Influence of flavonoid-rich fruit and vegetable intake on diabetic retinopathy
      and diabetes-related biomarkers.
AB  - OBJECTIVE: (1) Determine the relationship between dietary flavonoid-rich fruit
      and vegetable consumption on diabetes-related biomarkers (e.g., HgbA1c) and
      diabetic retinopathy. METHODS: Data from 381 participants with diabetes from the
      NHANES 2003-2006 were analyzed. Blood samples were taken to measure C-reactive
      protein (CRP), HgbA1C, and fasting glucose and insulin. Diabetic retinopathy was
      assessed from a retinal imaging exam. A high-flavonoid fruit and vegetable
      consumption (HFVC) index variable was created from a food frequency questionnaire
      (FFQ). RESULTS: After adjustments, greater HFVC was associated (p<0.05) with
      lower levels of CRP (beta=-0.005), HgbA1C (beta=-0.005) and glucose (beta=-0.59),
      with greater HFVC reducing the odds of having diabetic retinopathy by 30%.
      CONCLUSION: Adults with diabetes consuming more flavonoid-rich fruits and
      vegetables had lower degrees of inflammation, better glycemic control, and
      reduced odds of diabetic retinopathy.

PMID- 25055730
TI  - Tocotrienol modulates crucial lipid metabolism-related genes in differentiated
      3T3-L1 preadipocytes.
AB  - Obesity and other lipid metabolism-related diseases have become more prevalent in
      recent years due to drastic lifestyle changes and dietary patterns. Unsaturated
      vitamin E, tocotrienol (T3), represents one of the most fascinating naturally
      occurring compounds that has the potential to influence a broad range of
      mechanisms underlying abnormal lipid metabolism processes. However, its efficacy
      and mechanism have been uncertain due to scarcity of data concerning the effect
      of T3 on lipid metabolism. In this study, we report a series of fascinating
      experimental findings on how T3 affects lipid metabolism in differentiated 3T3-L1
      preadipocytes. Treatment with T3 (25 MUM), especially delta and gamma isomers,
      inhibited the accumulation of triglyceride and lipid droplets in differentiated
      3T3-L1 cells. This manifestation was supported by mRNA and protein expression of
      crucial lipid metabolism-related genes. The present study provides a novel set of
      data pertaining to the possibility of T3 as an anti-metabolic disorder agent. 

PMID- 25055731
TI  - Conservative management and female gender are associated with increased cancer
      specific death in patients with isolated primary urothelial carcinoma in situ.
AB  - Our goal was to investigate the effect of patient and disease characteristics on
      the probability of cancer-specific death (CSD) in cases of isolated urothelial
      carcinoma in situ (CIS). We performed a retrospective analysis of patients
      diagnosed with isolated CIS between 1990 and 2010 identified from the
      Surveillance, Epidemiology, and End Results (SEER) database. Competing risk
      analysis using Cox proportional hazard model was used to examine the probability
      of CSD controlling for possible covariates. Overall (n = 1432), patients were
      mainly male (75%), mean age at diagnosis was 71 years, median survival 47 months,
      and 65% of the patients had CIS in their upper urinary tract. Caucasians were the
      predominant race (90%). CIS was the cause of death in 87/1432(6%) of the total
      cohort; 69/1239 (6%) of patients who underwent surgery, and 18/193 (9%) of the
      patients who were managed conservatively (CM). On multivariate analysis, CM
      [hazard ration (HR) = 2.019, CI: 1.189-3.429, P = 0.009] and female gender (HR =
      1.690, CI: 1.041-2.741, P = 0.033) were associated with CSD, while age, site,
      race and year of diagnosis were non-significant predictors. Female gender and
      conservative management were positively associated with CSD. Multi-institutional
      collaboration is needed to validate markers for poor prognosis in cases of
      isolated CIS.

PMID- 25055732
TI  - Molecular modeling, synthesis and biological evaluation of N-heteroaryl compounds
      as reverse transcriptase inhibitors against HIV-1.
AB  - Different N-heteroaryl compounds bearing pyrimidine and benzimidazole moieties
      have been designed in silico using Discovery studio 2.5 software, synthesized and
      evaluated for their inhibitory activity as reverse transcriptase inhibitors
      against HIV-1 replication using laboratory adapted strains HIV-1IIIB (X4, subtype
      B) and HIV-1Ada5 (R5, subtype B), and the primary isolates HIV-1UG070 (X4,
      subtype D) and HIV-1VB59 (R5, subtype C). Cell-based assay showed that compounds
      were active at 1.394 MUm concentrations (Selectivity Index: 1.29-38.39). The
      studies on structure-activity relationship clearly suggested anti-HIV activity of
      pyrimidine and benzimidazole derivatives and these findings were consistent with
      the in vitro cell-based experimental data. The results of molecular modeling and
      docking confirmed that all compounds assumed a butterfly-like conformation and
      showed H-bond, 'pi-pi' and 'pi-+' and hydrophobic interactions within flexible
      non-nucleoside inhibitor binding pocket of HIV-1 reverse transcriptase, similar
      to known non-nucleoside reverse transcriptase inhibitors, such as nevirapine. In
      view of the results obtained, it can be said that the chemical skeletons of N, N'
      bis-(pyridin-2-yl)-succinamide (14 and 15) and 1, 4-bis-benzoimidazol-1-yl-butane
      1, 4-dione (16 and 17) may be used for developing potent inhibitors of HIV-1
      replication, with suitable structure/pharmacophore modifications.

PMID- 25055733
TI  - A psychometric comparison of two carer quality of life questionnaires in
      Huntington's disease: implications for neurodegenerative disorders - a response
      to: Hagell and Smith (2013) Journal of Huntington's Disease 2(3) 315-322.

PMID- 25055734
TI  - Why psychometrics is important - a response to: Aubeeluck, Buchanan & Stupple
      (2013) Journal of Huntington's Disease 2(4) 453-454.

PMID- 25055738
TI  - A nanospherical ordered mesoporous Lewis acid polymer for the direct
      glycosylation of unprotected and unactivated sugars in water.
AB  - The design of robust solid catalysts which can selectively synthesize highly
      functionalized carbohydrate derivatives from unprotected and unactivated simple
      sugars in water is an outstanding challenge. Herein we describe the preparation
      of a novel nanospherical ordered mesoporous Lewis acid polymer (Sc(OTf)2-NSMP) by
      functionalizing the mesoporous phenol-formaldehyde polymer framework with
      scandium triflate groups. In the C-glycosylation reaction between D-glucose and
      dimedone with the Sc(OTf)2-NSMP catalyst, the conversion was 99% and the yield of
      xanthone-C-glucoside reached 92% after 2 days, which exceeded the previous best
      results. It was shown that other xanthone glycosides can be obtained from various
      sugars with moderate to good yields. Furthermore, the catalyst can be easily
      recovered and reused at least seven times without loss of catalytic activity.

PMID- 25055737
TI  - Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid
      in platelet aggregation in acute myocardial infarction.
AB  - The aggregation of platelets on the plaque rupture site on the coronary artery is
      reported to cause both acute coronary syndromes (ACS) and acute myocardial
      infarction (AMI). While the inhibition of platelet aggregation by acetyl
      salicylic acid was reported to produce beneficial effects in ACS, it failed to do
      in AMI. The concentration of a stress induced protein (dermcidin isoform-2) was
      much higher in AMI than that in ACS. Incubation of normal platelet rich plasma
      (PRP) with dermcidin showed one high affinity (Kd = 40 nM) and one low affinity
      binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4 MUM
      dermcidin, the platelets became resistant to the inhibitory effect of aspirin
      similar to that in the case of AMI. Incubation of PRP from AMI with dermcidin
      antibody restored the sensitivity of the platelets to the aspirin effect.
      Incubation of AMI PRP pretreated with 15 MUM aspirin, a stimulator of the NO
      synthesis, resulted in the increased production of NO in the platelets that
      removed the bound dermcidin by 40% from the high affinity binding sites of AMI
      platelets. When the same AMI PRP was retreated with 10 MUM aspirin, the
      aggregation of platelets was completely inhibited by NO synthesis.

PMID- 25055739
TI  - Human RAD23 homolog A is required for the nuclear translocation of apoptosis
      inducing factor during induction of cell death.
AB  - BACKGROUND INFORMATION: During the initiation of cell death, mitochondrial
      protein, apoptosis-inducing factor (AIF), is transported to the nucleus. The
      mechanism of AIF nuclear translocation, however, is not clear. After protein
      synthesis, the AIF is originally targetted to the mitochondria, and the nuclear
      targetting is a secondary event. Therefore, we hypothesised that the nuclear
      translocation of AIF could be achieved by a novel pathway. RESULTS: By using
      yeast two-hybrid assay, we identified the human UV excision repair protein RAD23
      homolog A (hHR23A) interacts with AIF and their interaction was confirmed by co
      immunoprecipitation and fluorescence resonance energy transfer microscopy.
      Silencing the RAD23A gene expression inhibits the nuclear transportation of AIF
      and increases cisplatin resistance. Silencing the karyopherin alpha 2 (KPNA2)
      gene expression, however, did not affect the nuclear import of AIF. Moreover, 2,4
      dinitrophenol inhibits staurosporine-induced nuclear translocation of AIF and
      increases cisplatin resistance. CONCLUSIONS: These results suggest that hHR23A is
      required for the nuclear translocation of AIF during induction of cell death, and
      this process is energy dependent, but independent of karyopherins.

PMID- 25055740
TI  - Emission enhancement of a coplanar pi-conjugated gelator without any auxiliary
      substituents.
AB  - A linear coplanar carbazole-based benzoxazole derivative without any auxiliary
      moieties could gelatinize organic solvents, and exhibited emission enhancement
      owing to the J-aggregate formation. 

PMID- 25055741
TI  - Massive human rivaroxaban overdose.

PMID- 25055742
TI  - GrabBlur--a framework to facilitate the secure exchange of whole-exome and 
      genome SNV data using VCF files.
AB  - BACKGROUND: Next Generation Sequencing (NGS) of whole exomes or genomes is
      increasingly being used in human genetic research and diagnostics. Sharing NGS
      data with third parties can help physicians and researchers to identify causative
      or predisposing mutations for a specific sample of interest more efficiently. In
      many cases, however, the exchange of such data may collide with data privacy
      regulations. GrabBlur is a newly developed tool to aggregate and share NGS
      derived single nucleotide variant (SNV) data in a public database, keeping
      individual samples unidentifiable. In contrast to other currently existing SNV
      databases, GrabBlur includes phenotypic information and contact details of the
      submitter of a given database entry. By means of GrabBlur human geneticists can
      securely and easily share SNV data from resequencing projects. GrabBlur can ease
      the interpretation of SNV data by offering basic annotations, genotype
      frequencies and in particular phenotypic information - given that this
      information was shared - for the SNV of interest. TOOL DESCRIPTION: GrabBlur
      facilitates the combination of phenotypic and NGS data (VCF files) via a local
      interface or command line operations. Data submissions may include HPO (Human
      Phenotype Ontology) terms, other trait descriptions, NGS technology information
      and the identity of the submitter. Most of this information is optional and its
      provision at the discretion of the submitter. Upon initial intake, GrabBlur
      merges and aggregates all sample-specific data. If a certain SNV is rare, the
      sample-specific information is replaced with the submitter identity. Generally,
      all data in GrabBlur are highly aggregated so that they can be shared with others
      while ensuring maximum privacy. Thus, it is impossible to reconstruct complete
      exomes or genomes from the database or to re-identify single individuals. After
      the individual information has been sufficiently "blurred", the data can be
      uploaded into a publicly accessible domain where aggregated genotypes are
      provided alongside phenotypic information. A web interface allows querying the
      database and the extraction of gene-wise SNV information. If an interesting SNV
      is found, the interrogator can get in contact with the submitter to exchange
      further information on the carrier and clarify, for example, whether the latter's
      phenotype matches with phenotype of their own patient.

PMID- 25055743
TI  - Novel non-parametric models to estimate evolutionary rates and divergence times
      from heterochronous sequence data.
AB  - BACKGROUND: Early methods for estimating divergence times from gene sequence data
      relied on the assumption of a molecular clock. More sophisticated methods were
      created to model rate variation and used auto-correlation of rates, local clocks,
      or the so called "uncorrelated relaxed clock" where substitution rates are
      assumed to be drawn from a parametric distribution. In the case of Bayesian
      inference methods the impact of the prior on branching times is not clearly
      understood, and if the amount of data is limited the posterior could be strongly
      influenced by the prior. RESULTS: We develop a maximum likelihood method--Physher
      -that uses local or discrete clocks to estimate evolutionary rates and divergence
      times from heterochronous sequence data. Using two empirical data sets we show
      that our discrete clock estimates are similar to those obtained by other methods,
      and that Physher outperformed some methods in the estimation of the root age of
      an influenza virus data set. A simulation analysis suggests that Physher can
      outperform a Bayesian method when the real topology contains two long branches
      below the root node, even when evolution is strongly clock-like. CONCLUSIONS:
      These results suggest it is advisable to use a variety of methods to estimate
      evolutionary rates and divergence times from heterochronous sequence data.
      Physher and the associated data sets used here are available online at
      http://code.google.com/p/physher/.

PMID- 25055744
TI  - Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human
      osteoblasts.
AB  - OBJECTIVE: This study aimed to check the effect of zoledronic acid (ZA) at
      subtoxic dose on human osteoblasts (HOs) in terms of cell viability, apoptosis
      occurrence, and differentiation induction. ZA belongs to the family of
      bisphosphonates (BPs), largely used in the clinical practice for the treatment of
      bone diseases, often associated with jaw osteonecrosis onset. Their
      pharmacological action consists in the direct block of the osteoclast-mediated
      bone resorption along with indirect action on osteoblasts. MATERIALS AND METHODS:
      HOs were treated choosing the highest limit concentration (10(-5) M) which does
      not induce toxic effects. Live/dead staining, flow cytometry, mitochondrial
      membrane potential assay, osteocalcin western blotting, gp38 RT-PCR, collagen
      type I, PGE2, and IL-6 ELISA assays were performed. RESULTS: Similar viability
      level between control and ZA-treated samples is found along with no significant
      increase of apoptotic and necrotic cells in ZA-treated sample. To establish if an
      early apoptotic pathway was triggered, Bax expression and mitochondrial membrane
      potential were evaluated finding a higher protein expression in control sample
      and a good integrity of mitochondrial membrane in both experimental points. Type
      I collagen secretion and alkaline phosphatase (ALP) activity appear increased in
      ZA-treated sample, osteocalcin expression level is reduced in ZA-treated cells,
      whereas no modifications of gp38 mRNA level are evidenced. No statistical
      differences are identified in PGE2 secretion level whereas IL-6 secretion is
      lower in ZA-treated HOs with respect to control ones. CONCLUSIONS: These results
      highlight that ZA, delaying the osteoblastic differentiation process versus the
      osteocytic lineage, strengthens its pharmacological activity enhancing bone
      density. CLINICAL RELEVANCE: The knowledge of ZA effects on osteoblasts at
      subtoxic dose allows to improve therapeutic protocols in order to strengthen drug
      pharmacological activity through a combined action on both osteoclastic and
      osteoblastic cells.

PMID- 25055745
TI  - Quality of postoperative pain management after midfacial fracture repair--an
      outcome-oriented study.
AB  - OBJECTIVES: There is a lack of literature regarding the procedure-specific
      quality of acute postoperative pain management after midfacial fracture repair.
      The purpose of the presented prospective clinical study was to evaluate
      postoperative pain management after surgical repair of midfacial fractures.
      MATERIALS AND METHODS: Eighty-five adults were evaluated on the first
      postoperative day following midfacial repair using the questionnaire of the
      Quality Improvement in Postoperative Pain Management (QUIPS) project. The main
      outcome measures were patients' characteristics and clinical- and patient
      reported outcome parameters. RESULTS: Overall, pain on the first postoperative
      day was moderate. A significant correlation between process and outcome
      parameters could be shown. Duration of surgery above the calculated median was
      significantly associated with higher maximum pain intensity (p = 0.017). Patients
      requiring opioids in the recovery room presented significantly higher pain on
      activity (p = 0.029) and maximum pain (p = 0.035). Sleeping impairment (p =
      0.001) and mood disturbance (p = 0.008) were significantly more prevalent in
      patients undergoing repair of a centrolateral midfacial fracture. CONCLUSIONS:
      QUIPS is a simple and qualified tool to evaluate the procedure specific quality
      of acute postoperative pain management. Pain on the first postoperative day
      following midfacial fracture repair seems overall to be moderate. Nearly a third
      of the patients showed inadequate postoperative pain management. To prevent
      inadequate postoperative pain management, it is necessary to establish a
      continued procedure-specific outcome measurement.

PMID- 25055746
TI  - Mechanical loading influences the effects of bisphosphonates on human periodontal
      ligament fibroblasts.
AB  - OBJECTIVES: There is increasing evidence that bisphosphonates affect orthodontic
      tooth movement. The object of the study was to investigate the changes produced
      by tensile strain on human periodontal ligament fibroblasts (HPdLFs) treated with
      clodronate or zoledronate. MATERIALS AND METHODS: HPdLF were cultured with 5 and
      50 MUM clodronate or zoledronate for 48 h and applied to tensile strain (TS) (5
      and 10 %) for 12 h in vitro. Viability was verified by MTT assay and apoptosis
      rate via caspase 3/7 assay. Gene expression of receptor activator of nuclear
      factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) was investigated using
      real-time PCR. OPG was also analyzed by ELISA and RANKL by immunocytochemical
      staining. RESULTS: Zoledronate (50 MUM) reduced the viability of HPdLF (76 vs 100
      %) and combined with 5 % TS to 53 %. TS of 10 % and clodronate reduced viability
      to 79 % with increased caspase 3/7 activity. Clodronate (5 MUM) led to a slight
      increase of OPG gene expression, zoledronate (5 MUM) to a slight decrease.
      Combined with 5 % TS, both increased OPG gene expression (2-3-fold) and OPG
      synthesis. Zoledronate increased gene expression of RANKL (4-fold). Combined with
      5 % of TS, this increase was abolished. TS of 10 % in combination amplified
      increase of RANKL ending up with a 9-fold gene expression by clodronate and high
      RANKL protein synthesis. CONCLUSIONS: This study shows for the first time that
      mechanical loading alters the effects of bisphosphonates on viability, apoptosis
      rate, and OPG/RANKL system of HPdLF dependent on the applied strength. Low forces
      and bisphosphonates increase factors for bone apposition, whereas high forces
      combined with bisphosphonates stimulate osteoclastogenesis. CLINICAL RELEVANCE:
      Mechanical loading of periodontal ligament with high strengths should be avoided
      during bisphosphonate therapy.

PMID- 25055747
TI  - Reliability of recordings of subgingival calculus detected using an ultrasonic
      device.
AB  - OBJECTIVES: To assess the intra-examiner reliability of recordings of subgingival
      calculus detected using an ultrasonic device, and to investigate the influence of
      subject-, tooth- and site-level factors on the reliability of these subgingival
      calculus recordings. MATERIALS AND METHODS: On two occasions, within a 1-week
      interval, 147 adult periodontitis patients received a full-mouth clinical
      periodontal examination by a single trained examiner. Duplicate subgingival
      calculus recordings, in six sites per tooth, were obtained using an ultrasonic
      device for calculus detection and removal. RESULTS: Agreement was observed in 65
      % of the 22,584 duplicate subgingival calculus recordings, ranging 45 % to 83 %
      according to subject. Using hierarchical modeling, disagreements in the
      subgingival calculus duplicate recordings were more likely in all other sites
      than the mid-buccal, and in sites harboring supragingival calculus. Disagreements
      were less likely in sites with PD >=  4 mm and with furcation involvement  >= 
      degree 2. Bleeding on probing or suppuration did not influence the reliability of
      subgingival calculus. At the subject-level, disagreements were less likely in
      patients presenting with the highest and lowest extent categories of the
      covariate subgingival calculus. CONCLUSIONS AND CLINICAL RELEVANCE: The
      reliability of subgingival calculus recordings using the ultrasound technology is
      reasonable. The results of the present study suggest that the reliability of
      subgingival calculus recordings is not influenced by the presence of
      inflammation. Moreover, subgingival calculus can be more reliably detected using
      the ultrasound device at sites with higher need for periodontal therapy, i.e.,
      sites presenting with deep pockets and premolars and molars with furcation
      involvement.

PMID- 25055748
TI  - Design of stereoelectronically promoted super lewis acids and unprecedented
      chemistry of their complexes.
AB  - A new family of stereoelectronically promoted aluminum and scandium super Lewis
      acids is introduced on the basis of state-of-the-art computations. Structures of
      these molecules are designed to minimize resonance electron donation to central
      metal atoms in the Lewis acids. Acidity of these species is evaluated on the
      basis of their fluoride-ion affinities relative to the antimony pentafluoride
      reference system. It is demonstrated that introduced changes in the
      stereochemistry of the designed ligands increase acidity considerably relative to
      Al and Sc complexes with analogous monodentate ligands. The high stability of
      fluoride complexes of these species makes them ideal candidates to be used as
      weakly coordinating anions in combination with highly reactive cations instead of
      conventional Lewis acid-fluoride complexes. Further, the interaction of all
      designed molecules with methane is investigated. All studied acids form stable
      pentavalent-carbon complexes with methane. In addition, interactions of the
      strongest acid of this family with very weak bases, namely, H2, N2, carbon
      oxides, and noble gases were investigated; it is demonstrated that this compound
      can form considerably stable complexes with the aforementioned molecules. To the
      best of our knowledge, carbonyl and nitrogen complexes of this species are the
      first hypothetical four-coordinated carbonyl and nitrogen complexes of aluminum.
      The nature of bonding in these systems is studied in detail by various bonding
      analysis approaches.

PMID- 25055749
TI  - Lean mass, muscle strength and gene expression in community dwelling older men:
      findings from the Hertfordshire Sarcopenia Study (HSS).
AB  - Sarcopenia is associated with adverse health outcomes. This study investigated
      whether skeletal muscle gene expression was associated with lean mass and grip
      strength in community-dwelling older men. Utilising a cross-sectional study
      design, lean muscle mass and grip strength were measured in 88 men aged 68-76
      years. Expression profiles of 44 genes implicated in the cellular regulation of
      skeletal muscle were determined. Serum was analysed for circulating cytokines TNF
      (tumour necrosis factor), IL-6 (interleukin 6, IFNG (interferon gamma), IL1R1
      (interleukin-1 receptor-1). Relationships between skeletal muscle gene
      expression, circulating cytokines, lean mass and grip strength were examined.
      Participant groups with higher and lower values of lean muscle mass (n = 18) and
      strength (n = 20) were used in the analysis of gene expression fold change.
      Expression of VDR (vitamin D receptor) [fold change (FC) 0.52, standard error for
      fold change (SE) +/- 0.08, p = 0.01] and IFNG mRNA (FC 0.31; SE +/- 0.19, p =
      0.01) were lower in those with higher lean mass. Expression of IL-6 (FC 0.43; SE
      +/- 0.13, p = 0.02), TNF (FC 0.52; SE +/- 0.10, p = 0.02), IL1R1 (FC 0.63; SE +/-
      0.09, p = 0.04) and MSTN (myostatin) (FC 0.64; SE +/- 0.11, p = 0.04) were lower
      in those with higher grip strength. No other significant changes were observed.
      Significant negative correlations between serum IL-6 (R = -0.29, p = 0.005), TNF
      (R = -0.24, p = 0.017) and grip strength were demonstrated. This novel skeletal
      muscle gene expression study carried out within a well-characterized
      epidemiological birth cohort has demonstrated that lower expression of VDR and
      IFNG is associated with higher lean mass, and lower expression of IL-6, TNF,
      IL1R1 and myostatin is associated with higher grip strength. These findings are
      consistent with a role of proinflammatory factors in mediating lower muscle
      strength in community-dwelling older men.

PMID- 25055751
TI  - Complete primary treatment failure of adalimumab in a patient with
      photoaggravated psoriasis.

PMID- 25055750
TI  - Complexities of short-term mobility for sex work and migration among sex workers:
      violence and sexual risks, barriers to care, and enhanced social and economic
      opportunities.
AB  - Despite research on the health and safety of mobile and migrant populations in
      the formal and informal sectors globally, limited information is available
      regarding the working conditions, health, and safety of sex workers who engage in
      short-term mobility and migration. The objective of this study was to
      longitudinally examine work environment, health, and safety experiences linked to
      short-term mobility/migration (i.e., worked or lived in another city, province,
      or country) among sex workers in Vancouver, Canada, over a 2.5-year study period
      (2010-2012). We examined longitudinal correlates of short-term mobility/migration
      (i.e., worked or lived in another city, province, or country over the 3-year
      follow-up period) among 646 street and off-street sex workers in a longitudinal
      community-based study (AESHA). Of 646 sex workers, 10.84 % (n = 70) worked or
      lived in another city, province, or country during the study. In a multivariate
      generalized estimating equations (GEE) model, short-term mobility/migration was
      independently correlated with older age (adjusted odds ratio (AOR) 0.95, 95 %
      confidence interval (CI) 0.92-0.98), soliciting clients in indoor (in-call)
      establishments (AOR 2.25, 95 % CI 1.27-3.96), intimate partner condom refusal
      (AOR 3.00, 1.02-8.84), and barriers to health care (AOR 1.77, 95 % CI 1.08-2.89).
      In a second multivariate GEE model, short-term mobility for sex work (i.e.,
      worked in another city, province, or country) was correlated with client
      physical/sexual violence (AOR 1.92, 95 % CI 1.02-3.61). In this study,
      mobile/migrant sex workers were more likely to be younger, work in indoor sex
      work establishments, and earn higher income, suggesting that short-term mobility
      for sex work and migration increase social and economic opportunities. However,
      mobility and migration also correlated with reduced control over sexual
      negotiation with intimate partners and reduced health care access, and mobility
      for sex work was associated with enhanced workplace sexual/physical violence,
      suggesting that mobility/migration may confer risks through less control over
      work environment and isolation from health services. Structural and community-led
      interventions, including policy support to allow for more formal organizing of
      sex work collectives and access to workplace safety standards, remain critical to
      supporting health, safety, and access to care for mobile and migrant sex workers.

PMID- 25055753
TI  - Direct anisotropic growth of CdS nanocrystals in thermotropic liquid crystal
      templates for heterojunction optoelectronics.
AB  - The direct growth of CdS nanocrystals in functional solid-state thermotropic
      liquid crystal (LC) small molecules and a conjugated LC polymer by in situ
      thermal decomposition of a single-source cadmium xanthate precursor to fabricate
      LC/CdS hybrid nanocomposites is described. The influence of thermal annealing
      temperature of the LC/CdS precursors upon the nanomorphology, photophysics, and
      optoelectronic properties of the LC/CdS nanocomposites is systematically studied.
      Steady-state PL and ultrafast emission dynamics studies show that the charge
      transfer rates are strongly dependent on the thermal annealing temperature.
      Notably, annealing at liquid-crystal state temperature promotes a more organized
      nanomorphology of the LC/CdS nanocomposites with improved photophysics and
      optoelectronic properties. The results confirm that thermotropic LCs can be ideal
      candidates as organization templates for the control of organic/inorganic hybrid
      nanocomposites at the nanoscale level. The results also demonstrate that in situ
      growth of semiconducting nanocrystals in thermotropic LCs is a versatile route to
      hybrid organic/inorganic nanocomposites and optoelectronic devices. 

PMID- 25055754
TI  - Uni- and bipolar hemiarthroplasty with a modern cemented femoral component
      provides elderly patients with displaced femoral neck fractures with equal
      functional outcome and survivorship at medium-term follow-up.
AB  - INTRODUCTION: The choice between unipolar and bipolar hemiarthroplasty for
      treatment of displaced intracapsular femoral neck fractures in elderly patients
      still remains controversial. Our objective was to compare series of elderly
      individuals with a displaced femoral neck fracture treated with either a
      cemented, modular unipolar or bipolar prosthesis with the same femoral component.
      MATERIALS AND METHODS: A prospective, randomized controlled trial of 175
      displaced intracapsular femoral neck fractures in patients over 65 years was
      randomly allocated to unipolar (88) and to bipolar (87) hemiarthroplasty group.
      The primary end point was implant survival. Secondary end points included
      difference in ambulatory ability and mortality. Follow-up evaluations were
      performed at 2 months, at 1, 3 and 5 years. Implant and patient survival were
      followed until 2/2012. Survival analyses were performed using Kaplan-Meier curves
      with log-rank test. Data were analyzed using Chi-square test and Student's t
      test. RESULTS: Unipolar hemiarthroplasty group had a significantly higher
      dislocation rate when compared with bipolar hemiarthroplasty group. This did not
      translate into difference in revision rates at 8 years. Prosthetic survival ship
      was 0.98 (95% Cl 0.94-1.00) in the unipolar group and 0.97 (95% Cl 0.93-1.00) in
      the bipolar group. There were no statistically significant differences in
      ambulatory ability, possibility to return home mortality or early radiological
      acetabular erosion. There were significantly more one-time dislocations in the
      unipolar group, but there was no difference in incidence of revisions due to
      recurrent dislocations. The overall mortality rate was 6% at 30 days, 9% at 90
      days, 16% at 12 months, and 53% at 5 years. There was no difference in mortality
      between the groups. CONCLUSIONS: Unipolar hemiarthroplasty group had a
      significantly higher dislocation rate when compared with bipolar hemiarthroplasty
      group. However, both provide elderly patients with equal ambulatory ability and
      low revision rate at medium-term follow-up.

PMID- 25055755
TI  - Effects of menarcheal age on the anterior cruciate ligament injury risk factors
      during single-legged drop landing in female artistic elite gymnasts.
AB  - INTRODUCTION: Although numerous studies have demonstrated the relationship
      between maturation and lower extremity biomechanics during landing in team sport
      athletes, we are presently uninformed of any research that examined the single
      legged drop landing biomechanics of gymnasts. The purpose of this study is to
      investigate the effects of the menarcheal age on the lower extremity biomechanics
      during a single-legged drop landing in female artistic elite gymnasts. MATERIALS
      AND METHODS: Twenty-two female artistic elite gymnasts, between 9 and 36 years of
      age, participated in this study. The participants were divided into two groups
      pre- (n = 11) and post- (n = 11) menarche and asked to perform a single-legged
      drop landing on top of a 30 cm platform and land on a force plate. The
      statistical analysis consisted of the multivariate analysis with the level of
      significance set at p < 0.05. RESULTS: The post-menarche group showed a decrease
      in their maximum knee flexion angle and increase in their maximum knee abduction
      angle, maximum internal tibial rotation angle, maximum knee abduction moment, and
      hamstring-quadriceps muscle activity ratio compared with the pre-menarche group
      during the single-legged drop landing. CONCLUSIONS: The post-menarche group
      showed an increased noncontact anterior cruciate ligament injury risk, due to
      their greater knee loads, compared with the pre-menarche group.

PMID- 25055756
TI  - Arthroscopic pubic symphysis debridement and adductor enthesis repair in athletes
      with athletic pubalgia: technical note and video illustration.
AB  - We elaborately describe our novel arthroscopic technique of the symphysis pubis
      in athletes with osteitis pubis and concomitant adductor enthesopathy who fail to
      conservative treatment modalities. The symphysis pubis is debrided
      arthroscopically and the degenerated origin of adductor tendon (enthesis) is
      excised and reattached. With our surgical procedure the stability of the
      symphysis pubis is successfully preserved and the adductor longus enthesopathy
      simultaneously addressed in the same setting. 

PMID- 25055757
TI  - Effect of supraglottic and super-supraglottic swallows on tongue pressure
      production against hard palate.
AB  - The objectives of this study were to evaluate the state of tongue pressure
      production during supraglottic swallow (SS) and super-supraglottic swallow (SSS)
      performed by healthy adults, and to investigate the effects of these swallowing
      maneuvers on the oral stage of swallowing. The participants were 19 healthy
      individuals. Tongue pressure against the hard palate during swallowing was
      measured using a tongue pressure sensor sheet system with five pressure-sensitive
      points. The tasks comprised swallowing 5 mL of water by normal wet swallow, SS,
      and SSS, and the parameters for analysis were the duration, the maximal
      magnitude, and the integrated value of tongue pressure during swallowing. The
      duration of tongue pressure was significantly longer at the anterior-median part
      of the hard palate during both SS and SSS than with normal wet swallow. The
      maximal magnitude increased significantly only at the posterior part of the hard
      palate during SS, but at all points during SSS. The integrated value increased
      significantly only at the posterior-median part of the hard palate during SS, but
      at all points except the mid-median part of the hard palate during SSS. The
      maximal magnitude and integrated value were also significantly higher at the
      anterior-median and posterior circumferential parts during SSS than during SS.
      These results show that these two swallowing maneuvers, which are known primarily
      as techniques to protect the airway, also function to strengthen the tongue
      pressure produced by the contact between the tongue and the hard palate during
      swallowing and this effect is more pronounced during SSS.

PMID- 25055758
TI  - Dry eye disease is associated with deterioration of mental health in male
      Japanese university staff.
AB  - Dry eye disease (DED) is defined as a multifactorial disease of the tears and
      ocular surface that results in symptoms of discomfort, visual disturbance, and
      tear-film instability, with potential damage to the ocular surface. It is thought
      to be associated with reduced quality of life (QOL). The aim of the present study
      was to investigate the effects of DED on health-related QOL in Japanese
      university sedentary office workers who are daily users of visual display
      terminal. In this study, 163 university staff (99 male and 64 female), aged 23-69
      years, served as study subjects. Subjects were asked to answer the following
      three questions. (1) How often do your eyes feel dry? (2) How often do your eyes
      feel irritated? (3) Have you ever been diagnosed by a clinician as having dry eye
      syndrome? Sixty-eight subjects who answered "constantly," "often", or "sometimes"
      to both questions 1 and 2 were classified as the DED Group, and the remaining 95
      were defined as the Non-DED Group. QOL was assessed by the SF-36 questionnaire,
      which consisted of 36 items to produce three summary scores, namely, mental,
      physical, and role/social component summary scores. For males, the DED Group had
      significantly lower scores than the Non-DED Group for mental component summary
      (MCS) (P = 0.005). In multiple regression analysis, MCS scores were adversely
      related to DED in males (P = 0.015). DED was associated with worsened QOL. DED
      should be regarded as a factor that can lead to deterioration of mental health.

PMID- 25055759
TI  - Hydrogen transport in non-ideal crystalline materials.
AB  - Hydrogen-transport behaviour under (non-)isothermal conditions is discussed. An
      extended modelling approach based on the effective diffusion coefficient is
      outlined for arbitrary temperature programmes, defect properties and hydrogen
      loading pressures. The influence of mathematical terms, such as the trap
      equilibrium reaction or microstructural changes, is critically discussed and
      examples of thermal desorption spectra and isothermal diffusion behaviour are
      given. 

PMID- 25055760
TI  - Keeping it in the family: intergenerational transmission of violence in Cebu,
      Philippines.
AB  - While witnessing violence between parents is one of the most consistent
      correlates of experiencing intimate partner violence (IPV) in later life, little
      research exists in developing countries on the effects of witnessing
      interparental IPV on young adults' involvement with family violence. This study
      examines the relation between witnessing interparental IPV and young adults'
      subsequent use and experience with family intimidation and physical abuse (FIPA)
      in Cebu, Philippines. Using data from the Cebu Longitudinal Health and Nutrition
      Survey, recent use and experience of FIPA among 21-22 year old young adults was
      assessed through self-reports from the 2005 survey, and childhood witnessing of
      interparental IPV assessed from the 2002 survey. Multinomial logistic regression
      was used to examine the effect of witnessing interparental IPV on young adults'
      use and experience of FIPA. Among all young adults, witnessing paternal
      perpetration of IPV predicted using FIPA, and witnessing maternal perpetration
      predicted experiencing FIPA. Among young adult females only, witnessing
      reciprocal IPV between parents predicted experiencing FIPA. Witnessing paternal
      perpetration of IPV among young adult males, maternal perpetration among young
      adult females, and reciprocal interparental IPV among all young adults predicted
      young adults both using and experiencing FIPA. Violence prevention efforts should
      reach all family members through family centered interventions. School based
      curricula, which largely focus on intimate partner and peer violence, should
      recognize adolescents' use and experience of violence with family members, and
      design modules accordingly. Further research on gender differences in family
      violence is recommended.

PMID- 25055761
TI  - Factors associated with safe delivery service utilization among women in Sheka
      zone, southwest Ethiopia.
AB  - Attempts to predict pregnancy and childbirth complications before they occur have
      not been successful. Provision of safe delivery service for all births is
      considered to be a critical intervention for ensuring safe motherhood. Hence the
      aim of the study was to assess factors associated with safe delivery service
      utilization among women in Sheka Zone South West Ethiopia. A community based
      comparative cross sectional survey was conducted among 554 women in Sheka Zone
      from February to March 2008. Data were collected through structured pre-tested
      questionnaire and entered into Epinfo version 3.3. Analyses were done with SPSS
      version 13 computer software with which bivariate and multiple logistic
      regressions were carried out. Mothers who completed at least secondary school
      were more likely to give birth at health facility than those uneducated (AOR =
      3.26, 95 % CI 1.51-7.06). Women with birth order above four were less likely to
      give birth in a health facility than those with first order births (AOR = 0.21,
      95 %CI 0.10-0.43). Women who had encountered problems in their immediate birth
      and received prenatal care were more likely to give birth at health facilities
      AOR = 33.78 95 % CI 16.44-69.39) and (AOR = 2.55, 95 % CI 1.05-6.21)
      respectively. Factors associated with safe delivery service utilization are
      related to the women's socioeconomic status and obstetric experiences.
      Consequently promotion of maternal education, prenatal care utilization,
      information education and communication on obstetric risks and general health
      service expansion are needed to ensure safe delivery service. 

PMID- 25055762
TI  - A collection of open source applications for mass spectrometry data mining.
AB  - We present several bioinformatics applications for the identification and
      quantification of phosphoproteome components by MS. These applications include a
      front-end graphical user interface that combines several Thermo RAW formats to
      MASCOTTM Generic Format extractors (EasierMgf), two graphical user interfaces for
      search engines OMSSA and SEQUEST (OmssaGui and SequestGui), and three
      applications, one for the management of databases in FASTA format (FastaTools),
      another for the integration of search results from up to three search engines
      (Integrator), and another one for the visualization of mass spectra and their
      corresponding database search results (JsonVisor). These applications were
      developed to solve some of the common problems found in proteomic and
      phosphoproteomic data analysis and were integrated in the workflow for data
      processing and feeding on our LymPHOS database. Applications were designed
      modularly and can be used standalone. These tools are written in Perl and Python
      programming languages and are supported on Windows platforms. They are all
      released under an Open Source Software license and can be freely downloaded from
      our software repository hosted at GoogleCode.

PMID- 25055763
TI  - In situ distributed diagnostics of flowable electrode systems: resolving spatial
      and temporal limitations.
AB  - In this study, we have developed an in situ distributed diagnostics tool to
      investigate spatial and temporal effects in electrochemical systems based on
      flowable electrodes. Specifically, an experimental approach was developed that
      enables spatially-resolved voltage measurements to be obtained in situ, in real
      time. To extract additional data from these distributed measurements, an
      experimentally-parameterized equivalent circuit model with a new 'flow capacitor'
      circuit element was developed to predict the distributions of various system
      parameters during operation. As a case study, this approach was applied to
      investigate the behavior of the suspension electrodes used in an electrochemical
      flow capacitor under flowing and static conditions. The volumetric capacitance is
      reduced from 15.6 F ml(-1) to 1.1 F ml(-1) under flowing conditions. Results
      indicate that the majority of the charging in suspension electrodes occurs within
      ~750 MUm of the current collectors during flow, which gives rise to significant
      state-of-charge gradients across the cell, as well as underutilization of the
      available active material. The underlying cause of this observation is attributed
      to the relatively high electrical resistance of the slurry coupled with a
      stratified charging regime and insufficient residence time. The observations
      highlight the need to develop more conductive slurries and to design cells with
      reduced charge transport lengths. 

PMID- 25055764
TI  - Care-related pain in hospitalized patients: severity and patient perception of
      management.
AB  - BACKGROUND: Hospitalized patients commonly undergo painful procedures, but little
      is known about care-related pain (CRP) in the overall population of inpatients.
      We conducted a cross-sectional 1-day survey to assess the prevalence and
      characteristics of CRP and its management in all units of a university hospital
      in Paris and determined the factors linked to severe CRP. METHODS: All patients
      who were able to communicate and were hospitalized for at least 24 h but not in a
      day-care or neonatal unit were included. RESULTS: From 938 patients who completed
      the questionnaire, 554 patients reported pain within the previous 24 h, for a 59%
      prevalence of pain, and 540 (58%) had experienced CRP in the previous 15 days
      (51% males; mean [SD] age 54 [18] years). Of 907 procedures, 330 (37%) resulted
      in severe pain. The most-often reported painful procedures were vascular
      punctures and patient mobilization. Severe CRP was associated with long
      hospitalization; non-vascular invasive punctures, catheterization, mobilization
      or radiological examination; or pain during the previous 24 h due to surgery or
      treatment. Only half of the patients declared that they had received information
      regarding the painful procedure. Treatment for pain was proposed and delivered in
      less than one quarter of cases. CONCLUSIONS: Our results of a survey of pain
      management in hospitalized patients relate to a wide variety of medical
      conditions and procedures. Health-care workers should be more systematic in
      managing CRP, and attention should be paid to patients at greatest risk of severe
      CRP.

PMID- 25055765
TI  - Syndemic factors associated with HIV risk for gay and bisexual men: comparing
      latent class and latent factor modeling.
AB  - Syndemics theory has been proposed as a framework for understanding the role of
      multiple risk factors driving the HIV epidemic among gay and bisexual men.
      Previous studies have examined five syndemic indicators (polydrug use,
      depression, childhood sexual abuse, sexual compulsivity, and intimate partner
      violence). Many of these studies have utilized sum scores, the total number of
      syndemic factors endorsed, to quantify syndemic stress. This approach assumes a
      unidimensional latent factor and equivalence of factor loadings. It also
      overlooks the possibility that patterns, or classes, of syndemic factor
      endorsement may be present. The current study utilized survey data from 669 gay
      and bisexual men to test assumptions of unidimensionality and factor loading
      equivalence and to examine the utility of identifying latent classes of syndemic
      stress. Analysis supported operationalizing syndemics as a unidimensional latent
      factor. Assumptions of loading equality were not supported. Meaningful profiles
      of syndemic stress were not evident in latent class analysis results. 

PMID- 25055767
TI  - Error-prone PCR and effective generation of gene variant libraries for directed
      evolution.
AB  - Any single-enzyme directed evolution strategy has two fundamental requirements:
      the need to efficiently introduce variation into a gene of interest and the need
      to create an effective library from those variants. Generation of a maximally
      diverse gene library is particularly important when employing nontargeted
      mutagenesis strategies such as error-prone PCR (epPCR), which seek to explore
      very large areas of sequence space. Here we present comprehensive protocols and
      tips for using epPCR to generate gene variants that exhibit a relatively balanced
      spectrum of mutations and for capturing as much diversity as possible through
      effective cloning of those variants. The detailed library preparation methods
      that we describe are generally applicable to any directed evolution strategy that
      uses restriction enzymes to clone gene variants into an expression plasmid. 

PMID- 25055766
TI  - Effect of directly observed antiretroviral therapy compared to self-administered
      antiretroviral therapy on adherence and virological outcomes among HIV-infected
      prisoners: a randomized controlled pilot study.
AB  - The effect of directly observed therapy (DOT) versus self-administered therapy
      (SAT) on antiretroviral (ART) adherence and virological outcomes in prison has
      never been assessed in a randomized, controlled trial. Prisoners were randomized
      to receive ART by DOT or SAT. The primary outcome was medication adherence
      [percent of ART doses measured by the medication event monitoring system (MEMS)
      and pill counts] at the end of 24 weeks. The changes in the plasma viral loads
      from baseline and proportion of participants virological suppressed (<400
      copies/mL) at the end of 24 weeks were assessed. Sixty-six percent (90/136) of
      eligible prisoners declined participation. Participants in the DOT arm (n = 20)
      had higher viral loads than participants in the SAT (n = 23) arm (p = 0.23).
      Participants, with complete data at 24 weeks, were analyzed as randomized. There
      were no significant differences in median ART adherence between the DOT (n = 16,
      99% MEMS [IQR 93.9, 100], 97.1 % pill count [IQR 95.1, 99.3]) and SAT (n = 21,
      98.3 % MEMS [IQR 96.0, 100], 98.5 % pill count [95.8, 100]) arms (p = 0.82 MEMS,
      p = 0.40 Pill Count) at 24 weeks. Participants in the DOT arm had a greater
      reduction in viral load of approximately -1 log 10 copies/mL [IQR -1.75, -0.05]
      compared to -0.05 [IQR -0.45, 0.51] in the SAT arm (p value = 0.02) at 24 weeks.
      The proportion of participants achieving virological suppression in the DOT vs
      SAT arms was not statistically different at 24 weeks (53 % vs 32 %, p = 0.21).
      These findings suggest that DOT ART programs in prison settings may not offer any
      additional benefit on adherence than SAT programs.

PMID- 25055768
TI  - Error-prone rolling circle amplification greatly simplifies random mutagenesis.
AB  - We describe a simple and easy protocol to introduce random mutations into plasmid
      DNA: error-prone rolling circle amplification. A template plasmid is amplified
      via rolling circle amplification with decreased fidelity in the presence of MnCl2
      and is used to transform a host strain resulting in a mutant library with several
      random point mutations per kilobase through the entire plasmid. The primary
      advantage of this method is its simplicity. This protocol does not require the
      design of specific primers or thermal cycling. The reaction mixture can be used
      for direct transformation of a host strain. This method allows rapid preparation
      of randomly mutated plasmid libraries, enabling wider application of random
      mutagenesis. 

PMID- 25055769
TI  - Random mutagenesis by error-prone pol plasmid replication in Escherichia coli.
AB  - Directed evolution is an approach that mimics natural evolution in the laboratory
      with the goal of modifying existing enzymatic activities or of generating new
      ones. The identification of mutants with desired properties involves the
      generation of genetic diversity coupled with a functional selection or screen.
      Genetic diversity can be generated using PCR or using in vivo methods such as
      chemical mutagenesis or error-prone replication of the desired sequence in a
      mutator strain. In vivo mutagenesis methods facilitate iterative selection
      because they do not require cloning, but generally produce a low mutation density
      with mutations not restricted to specific genes or areas within a gene. For this
      reason, this approach is typically used to generate new biochemical properties
      when large numbers of mutants can be screened or selected. Here we describe
      protocols for an advanced in vivo mutagenesis method that is based on error-prone
      replication of a ColE1 plasmid bearing the gene of interest. Compared to other in
      vivo mutagenesis methods, this plasmid-targeted approach allows increased
      mutation loads and facilitates iterative selection approaches. We also describe
      the mutation spectrum for this mutagenesis methodology in detail, and, using
      cycle 3 GFP as a target for mutagenesis, we illustrate the phenotypic diversity
      that can be generated using our method. In sum, error-prone Pol I replication is
      a mutagenesis method that is ideally suited for the evolution of new biochemical
      activities when a functional selection is available. 

PMID- 25055770
TI  - The Sequence Saturation Mutagenesis (SeSaM) method.
AB  - Sequence Saturation Mutagenesis (SeSaM) is a random mutagenesis method developed
      to overcome the limitations of existing error-prone PCR (epPCR) protocols. SeSaM
      is advantageous with respect to (1) elimination of mutagenic "hot spots", (2)
      increase in frequency of subsequent nucleotide substitutions, (3) control over
      the mutational bias through the utilization of universal base analogs, and,
      consequently, (4) the prospect of generating transversion-enriched mutant
      libraries. These advanced features lead to chemically diverse mutant libraries on
      the protein level, essentially making SeSaM a complementary technology to
      transition biased epPCR mutagenesis methods. 

PMID- 25055771
TI  - Generation of effective libraries by neutral drift.
AB  - Neutral drift is a recently developed experimental technique used to identify
      superior starting points for protein engineering. Neutral drift explores
      accessible sequence space by repeated rounds of mutagenesis and selection to
      maintain wild-type function. Mutations that are largely neutral for the native
      function accumulate, and those that are highly detrimental are purged, yielding a
      library of high diversity and quality. This technique is useful in situations
      where laboratory evolution is at a dead end, i.e., when the enzyme activity
      intended for evolution proves recalcitrant to improvements or is too low to be
      detected. 

PMID- 25055772
TI  - Site-saturation mutagenesis by overlap extension PCR.
AB  - Site-saturation mutagenesis is a proven strategy for generating high-quality
      variant gene libraries of a defined size. Variation is introduced via
      incorporation of degenerate base combinations at specific codon locations, giving
      rise to a precise series of amino acid substitutions in the encoded protein. Here
      we describe a simple and efficient overlap PCR protocol for the introduction of
      degenerate bases at either single or multiple codon locations. The resulting
      libraries can then be directly screened for improved protein function as either
      an independent directed evolution study or an adjunct to random mutagenesis
      strategies (such as error-prone PCR) that are, in isolation, unlikely to access
      the full repertoire of possible amino acid substitutions at any given position. 

PMID- 25055773
TI  - Iterative saturation mutagenesis: a powerful approach to engineer proteins by
      systematically simulating Darwinian evolution.
AB  - Iterative saturation mutagenesis (ISM) is a widely applicable and powerful
      strategy for the efficient directed evolution of enzymes. First, one or more
      amino acid positions from the chosen enzyme are assigned to multi-residue sites
      (i.e., groups of amino acids or "multisites"). Then, the residues in each
      multisite are mutated with a user-defined randomization scheme to all canonical
      amino acids or a reduced amino acid alphabet. Subsequently, the genes of chosen
      variants (usually the best but not necessarily) are used as templates for
      saturation mutagenesis at other multisites, and the process is repeated until the
      desired degree of biocatalyst improvement has been achieved. Addressing
      multisites iteratively results in a so-called ISM scheme or tree with various
      upward branches or pathways. The systematic character of ISM simulates in vitro
      the natural process of Darwinian evolution: variation (library creation),
      selection (library screening), and amplification (template chosen for the next
      round of randomization). However, the main feature of ISM that distinguishes it
      from other directed evolution methods is the systematic probing of a defined
      segment of the protein sequence space, as it has been shown that ISM is much more
      efficient in terms of biocatalyst optimization than random methods such as error
      prone PCR. In addition, ISM trees have also shed light on the emergence of
      epistasis, thereby rationally improving the strategies for evolving better
      enzymes. ISM was developed to improve catalytic properties such as rate,
      substrate scope, stereo- and regioselectivity using the Combinatorial Active-site
      Saturation Test (CAST), as well as chemical and thermal stability employing the B
      Factor Iterative Test (B-FIT). However, ISM can also be invoked to manipulate
      such protein properties as binding affinity among other possibilities, including
      protein-protein interactions. Herein, we provide general guidelines for ISM,
      using CAST as the case study in the quest to enhance the activity and
      regioselectivity of the monooxygenase P450BM3 toward testosterone. 

PMID- 25055774
TI  - Generating targeted libraries by the combinatorial incorporation of synthetic
      oligonucleotides during gene shuffling (ISOR).
AB  - Protein engineering by directed evolution relies on the use of libraries enriched
      with beneficial variants. Such libraries should explore large mutational
      diversities while avoiding high loads of deleterious mutations. Here we describe
      a simple protocol for incorporating synthetic oligonucleotides that encode
      designed, site-specific mutations by assembly PCR. This protocol enables a
      researcher to "hedge the bets," namely, to explore a large number of potentially
      beneficial mutations in a combinatorial manner such that individual library
      variants carry a limited number of mutations. 

PMID- 25055775
TI  - OmniChange: simultaneous site saturation of up to five codons.
AB  - Multi-site-saturation mutagenesis allows altering of "localizable" properties
      such as activity and selectivity and enables the discovery of cooperative amino
      acid substitutions which are unlikely to be discovered by saturating single
      codons individually or iteratively. The herein presented method "OmniChange" does
      not require any DNA modifying enzyme (e.g., endonucleases or ligases), and
      diverse mutant libraries with up to five simultaneously saturated positions are
      generated in a robust and technically simple manner in four steps. The key
      feature of the OmniChange method is a highly efficient chemical cleavage of
      phosphorothiolated nucleotides by ethanol-iodine to generate 12-nucleotide-long
      5' overhangs in double-stranded DNA. The generated vector and inserts can be
      hybridized in a one-pot assembly leading to fully functional mutagenic plasmids,
      and the employed E. coli host can easily ligate up to 10 DNA nicks without any
      further enzymatic treatment. OmniChange is furthermore a reliable and general
      tool for multi-DNA fragment assembly which is DNA sequence independent. 

PMID- 25055776
TI  - Random insertional-deletional strand exchange mutagenesis (RAISE): a simple
      method for generating random insertion and deletion mutations.
AB  - Although proteins can be artificially improved by random insertion and deletion
      mutagenesis methods, these procedures are technically difficult. Here we describe
      a simple method called random insertional-deletional strand exchange mutagenesis
      (RAISE). This method is based on gene shuffling and can be used to introduce a
      wide variety of insertions, deletions, and substitutions. RAISE involves three
      steps: DNA fragmentation, attachment of a random short sequence, and
      reconstruction. This yields unique mutants and can be a powerful technique for
      protein engineering. 

PMID- 25055777
TI  - Transposon-based approaches for generating novel molecular diversity during
      directed evolution.
AB  - This chapter introduces a set of transposon-based methods that were developed to
      sample trinucleotide deletion, trinucleotide replacement, and domain insertion.
      Each approach has a common initial step that utilizes an engineered version of
      the Mu transposon called MuDel. The inherent low sequence specificity of MuDel
      results in its random insertion into target DNA during in vitro transposition.
      Removal of the transposon using a type IIS restriction endonuclease generates
      blunt-end random breaks at a frequency of one per target gene and the concomitant
      loss of 3 bp. Self-ligation or insertion of another DNA cassette results in the
      sampling of trinucleotide deletion or trinucleotide substitution/domain
      insertion, respectively. 

PMID- 25055778
TI  - Restriction enzyme-mediated DNA family shuffling.
AB  - DNA shuffling is an established recombinatorial method that was originally
      developed to increase the speed of directed evolution experiments beyond what
      could be accomplished using error-prone PCR alone. To achieve this, mutated
      copies of a protein-coding sequence are fragmented with DNase I and the fragments
      are then reassembled in a PCR without primers. The fragments anneal where there
      is sufficient sequence identity, resulting in full-length variants of the
      original gene that have inherited mutations from multiple templates. Subsequent
      studies demonstrated that directed evolution could be further accelerated by
      shuffling similar native protein-coding sequences from the same gene family,
      rather than mutated variants of a single gene. Generally at least 65-75 % global
      identity between parental sequences is required in DNA family shuffling, with
      recombination mostly occurring at sites with at least five consecutive
      nucleotides of local identity. Since DNA shuffling was originally developed, many
      variations on the method have been published. In particular, the use of
      restriction enzymes in the fragmentation step allows for greater customization of
      fragment lengths than DNase I digestion and avoids the risk that parental
      sequences may be over-digested into unusable very small fragments. Restriction
      enzyme-mediated fragmentation also reduces the occurrence of undigested parental
      sequences that would otherwise reduce the number of unique variants in the
      resulting library. In the current chapter, we provide a brief overview of the
      alternative methods currently available for DNA shuffling as well as a protocol
      presented here that improves on several previous implementations of restriction
      enzyme-mediated DNA family shuffling, in particular with regard to purification
      of DNA fragments for reassembly. 

PMID- 25055779
TI  - Assembly of Designed Oligonucleotides: a useful tool in synthetic biology for
      creating high-quality combinatorial DNA libraries.
AB  - The method dubbed Assembly of Designed Oligonucleotides (ADO) is a powerful tool
      in synthetic biology to create combinatorial DNA libraries for gene, protein,
      metabolic, and genome engineering. In directed evolution of proteins, ADO
      benefits from using reduced amino acid alphabets for saturation mutagenesis
      and/or DNA shuffling, but all 20 canonical amino acids can be also used as
      building blocks. ADO is performed in a two-step reaction. The first involves a
      primer-free, polymerase cycling assembly or overlap extension PCR step using
      carefully designed overlapping oligonucleotides. The second step is a PCR
      amplification using the outer primers, resulting in a high-quality and bias-free
      double-stranded DNA library that can be assembled with other gene fragments
      and/or cloned into a suitable plasmid subsequently. The protocol can be performed
      in a few hours. In theory, neither the length of the DNA library nor the number
      of DNA changes has any limits. Furthermore, with the costs of synthetic DNA
      dropping every year, after an initial investment is made in the oligonucleotides,
      these can be exchanged for alternative ones with different sequences at any point
      in the process, fully exploiting the potential of creating highly diverse
      combinatorial libraries. In the example chosen here, we show the construction of
      a high-quality combinatorial ADO library targeting sixteen different codons
      simultaneously with nonredundant degenerate codons encoding various reduced
      alphabets of four amino acids along the heme region of the monooxygenase P450
      BM3. 

PMID- 25055780
TI  - One-pot Simple methodology for CAssette Randomization and Recombination for
      focused directed evolution (OSCARR).
AB  - The OSCARR methodology (One-pot Simple methodology for CAssette Randomization and
      Recombination) bridges the gap between site-directed mutagenesis and full
      randomization by making use of carefully designed mutagenic cassettes and an
      optimized one-pot megaprimer PCR. The method is especially suited to construct
      libraries of up to ten randomized codons for focused directed evolution, exhibits
      up to 97 % efficiency in the amplification of mutated over wild-type products,
      and is sufficiently versatile to allow mutagenesis and recombination of several
      cassettes within the same gene. 

PMID- 25055781
TI  - USER friendly DNA recombination (USERec): gene library construction requiring
      minimal sequence homology.
AB  - USER friendly DNA recombination (USERec) is based on near homology-independent
      recombination of DNA fragments (~40-400 bp) that are efficiently reassembled into
      full-length genes, proven for up to ten fragments. USERec requires a minimal
      crossover sequence (a 5'-AN(4-8)T-3' motif) of the fragments that can be
      implemented wherever structural or functional comparisons suggest a fragment
      boundary. The greatly reduced sequence constraints of this method facilitate
      directional assembly of gene fragments for applications such as exon or domain
      shuffling, loop grafting, reassembly of natural modular biosynthetic assembly
      lines, and rearrangement of structurally (but not sequence) homologous proteins.

PMID- 25055782
TI  - ITCHY: Incremental Truncation for the Creation of Hybrid enzYmes.
AB  - Incremental Truncation for the Creation of Hybrid enzYmes (ITCHY) is a directed
      evolution technique for randomly recombining two genes. The chief advantage of
      ITCHY is that there is no requirement for the two genes to share any sequence
      similarity. This distinguishes ITCHY from directed evolution methods that are
      based on homologous recombination, such as DNA shuffling. In ITCHY, Escherichia
      coli exonuclease III is used to incrementally truncate one of the parental genes
      from its 3' end and the other from its 5' end. Ligation of the randomly truncated
      gene fragments yields a combinatorial library of chimeras. In this chapter, we
      provide detailed protocols for constructing libraries using both the user
      friendly thio-ITCHY method and also time-dependent incremental truncation. We
      illustrate the protocols with the data that we obtained when we recombined two
      alcohol dehydrogenase genes that only share 47 % sequence identity. 

PMID- 25055783
TI  - Generating random circular permutation libraries.
AB  - Protein engineering by random circular permutation is an effective tool for
      tailoring protein topology with potential functional benefits including improved
      catalytic activity. This method involves covalently connecting the native protein
      termini with a peptide linker and cleaving a peptide bond elsewhere in the
      polypeptide sequence. Termini relocation can impact protein ternary and
      quaternary structure and translate into functional enhancements due to changes in
      protein conformation and flexibility. As the effects of new termini in specific
      protein locations are difficult to predict, the preparation of a library
      constituting all possible permutation sites is an effective search strategy for
      identifying variants with novel properties. 

PMID- 25055784
TI  - Probabilistic methods in directed evolution: library size, mutation rate, and
      diversity.
AB  - Directed evolution has emerged as an important tool for engineering proteins with
      improved or novel properties. Because of their inherent reliance on randomness,
      directed evolution protocols are amenable to probabilistic modeling and analysis.
      This chapter summarizes and reviews in a nonmathematical way some of the
      probabilistic works related to directed evolution, with particular focus on three
      of the most widely used methods: saturation mutagenesis, error-prone PCR, and in
      vitro recombination. The ultimate aim is to provide the reader with practical
      information to guide the planning and design of directed evolution studies.
      Importantly, the applications and locations of freely available computational
      resources to assist with this process are described in detail. 

PMID- 25055785
TI  - The Mutagenesis Assistant Program.
AB  - Mutagenesis Assistant Program (MAP) is a web-based statistical tool to develop
      directed evolution strategies by investigating the consequences at the amino acid
      level of the mutational biases of random mutagenesis methods on any given gene.
      The latest development of the program, the MAP(2.0)3D server, correlates the
      generated amino acid substitution patterns of a specific random mutagenesis
      method to the sequence and structural information of the target protein. The
      combined information can be used to select an experimental strategy that improves
      the chances of obtaining functionally efficient and/or stable enzyme variants.
      Hence, the MAP(2.0)3D server facilitates the "in silico" prescreening of the
      target gene by predicting the amino acid diversity generated in a random
      mutagenesis library. Here, we describe the features of MAP(2.0)3D server by
      analyzing, as an example, the cytochrome P450BM3 monooxygenase (CYP102A1). The
      MAP(2.0)3D server is available publicly at http://map.jacobs
      university.de/map3d.html.

PMID- 25055786
TI  - Computational tools for designing smart libraries.
AB  - Traditional directed evolution experiments are often time-, labor- and cost
      intensive because they involve repeated rounds of random mutagenesis and the
      selection or screening of large mutant libraries. The efficiency of directed
      evolution experiments can be significantly improved by targeting mutagenesis to a
      limited number of hot-spot positions and/or selecting a limited set of
      substitutions. The design of such "smart" libraries can be greatly facilitated by
      in silico analyses and predictions. Here we provide an overview of computational
      tools applicable for (a) the identification of hot-spots for engineering enzyme
      properties, and (b) the evaluation of predicted hot-spots and selection of
      suitable amino acids for substitutions. The selected tools do not require any
      specific expertise and can easily be implemented by the wider scientific
      community. 

PMID- 25055787
TI  - Computational tools for directed evolution: a comparison of prospective and
      retrospective strategies.
AB  - Directed evolution methods have proved to be highly effective in the design of
      novel proteins and in the generation of large libraries of diverse sequences.
      However, searching through the vast number of mutants produced during such
      experiments in order to find the best represents a daunting and difficult task.
      In recent years, a number of computational tools have been developed to provide
      guidance during this exploratory process. It can, however, be unclear as to which
      tool or tools best complement the chosen library design strategy. In this review,
      we describe and critically evaluate some of the more notable tools in this area,
      discussing the rationale behind each, the requirements for their implementation,
      and potential issues faced when using them. Some examples of their application in
      an experimental setting are also provided. The tools have been classified based
      on contrasting strategies as to how they function: prospective tools SCHEMA and
      OPTCOMB use extant sequence and structural data to predict optimal locations for
      crossover sites, whereas retrospective tools ProSAR and ASRA use property data
      from the mutant library to predict beneficial mutations and features. From our
      evaluation, we suggest that each tool can play a role in the design process;
      however this is largely dictated by the data available and the desired
      experimental strategy for the project. 

PMID- 25055788
TI  - Designing libraries of chimeric proteins using SCHEMA recombination and RASPP.
AB  - SCHEMA is a method for designing libraries of novel proteins by recombination of
      homologous sequences. The goal is to maximize the number of folded proteins while
      simultaneously generating significant sequence diversity. Here, we use the RASPP
      algorithm to identify optimal SCHEMA designs for shuffling contiguous elements of
      sequence. To exemplify the method, SCHEMA is used to recombine five fungal
      cellobiohydrolases (CBH1s) to produce a library of more than 390,000 novel CBH1
      sequences. 

PMID- 25055789
TI  - Noncontiguous SCHEMA protein recombination.
AB  - SCHEMA is a method of designing protein recombination libraries that contain a
      large fraction of functional proteins with a high degree of mutational diversity.
      In the previous chapter, we illustrated the method for designing libraries by
      swapping contiguous sequence elements. Here, we introduce the NCR ("noncontiguous
      recombination") algorithm to identify optimal designs for swapping elements that
      are contiguous in the 3-D structure but not necessarily in the primary sequence.
      To exemplify the method, NCR is used to recombine three fungal cellobiohydrolases
      (CBH1s) to produce a library containing more than 500,000 novel chimeric
      sequences. 

PMID- 25055790
TI  - Engineering proteins by reconstructing evolutionary adaptive paths.
AB  - Reconstructing evolutionary adaptive paths (REAP) is a low-throughput technique
      used to design protein libraries that can be assayed for specific properties such
      as catalytic function or thermostability. This approach takes advantage of
      natural selection by using theoretical ancestral proteins as the foundation for
      library variants. REAP gives rise to smaller libraries but with a higher ratio of
      viable proteins than other high-throughput techniques. REAP uses analyses of
      ancestral sequences and signatures of functional divergence to modify extant
      protein sequences. This allows the experimenter to statistically evaluate which
      amino acid mutations in which sites within the protein are most likely to produce
      functional proteins having varied phenotypes. 

PMID- 25055791
TI  - Cost-effectiveness of asenapine in the treatment of patients with bipolar I
      disorder with mixed episodes in an Italian context.
AB  - INTRODUCTION: Bipolar disorder is a chronic disease characterized by periods of
      mania or hypomania, depression, or a combination of both (mixed state). Because
      bipolar disorder is one of the leading causes of disability, it represents an
      important economic burden on society. Asenapine (ASE) is a new second-generation
      antipsychotic developed and approved for the treatment of manic or mixed episodes
      associated with bipolar disorder. The objective of the present study was to
      assess the cost-effectiveness of ASE compared to olanzapine (OLA) in the
      treatment of patients experiencing mixed episodes associated with bipolar I
      disorder in the context of the Italian National Health Service (NHS). METHODS: A
      pharmacoeconomic model was developed to simulate the management of Italian
      bipolar I patients with mixed episodes over a 5-year time horizon by combining
      clinical parameters with resource utilization. An expert panel of Italian
      psychiatrists and health economists was responsible for adapting a UK model to
      the Italian context. The primary outcome measure of the economic evaluation was
      the incremental cost effectiveness ratio, where effectiveness is measured in
      terms of quality adjusted life-years gained. Scenario analyses, sensitivity
      analyses, and a probabilistic sensitivity analysis were performed to test the
      robustness of the model. RESULTS: This pharmacoeconomic model showed that ASE
      resulted to be dominant over OLA; in fact, ASE was associated with lower direct
      costs (derived largely by the savings from hospitalizations avoided) and also
      generated a better quality of life. Results were robust to changes in key
      parameters; both scenario analyses and sensitivity analyses demonstrated model
      reliability. CONCLUSIONS: Results from this study suggest that the management of
      bipolar I patients with mixed episodes using ASE as alternative to OLA can lead
      to cost saving for the Italian NHS and improve patients quality of life.

PMID- 25055792
TI  - A review on schizophrenia and relapse--a quest for user-friendly 
      psychopharmacotherapy.
AB  - OBJECTIVE: Schizophrenia in general is notoriously associated with relapses
      rendering the illness progressive to worse outcomes, a concept of which is
      compatible with neurotoxicity. Therefore, relapse prevention is of utmost
      clinical relevance. METHODS: In this review, we aim to put relapse into clinical
      context in the realm of natural history of, or heterogeneity in, schizophrenia
      and summarize risk factors of relapse. We discuss how to effectively 'define'
      relapse in schizophrenia and recent meta-analytic studies on this topic to
      highlight the importance of continuous antipsychotic treatment. RESULTS: The
      following issues emerged: 'How low maintenance antipsychotic dosage could be?',
      'How extended dosing could be?', 'Who could be successfully withdrawn from
      antipsychotics?' and 'How relapse could be defined in the first place?' The
      question in particular is how better to deliver antipsychotics at the lowest
      possible, whereby dose and dosing interval are relevant. While ongoing
      antipsychotic treatment is the rule, recent works are pointing to a possibility
      of lower dosage in the maintenance phase of the illness. CONCLUSIONS: Bearing in
      mind that suboptimal adherence and withdrawal from antipsychotics are an
      established and unequivocal risk factor for relapse, further investigations are
      certainly needed to explore user-friendly manner of psychopharmacotherapy to
      prevent relapse in schizophrenia.

PMID- 25055793
TI  - The significance of autophagy in colorectal cancer   pathogenesis and
      implications for therapy.
AB  - Colorectal cancer (CRC) is one of the most common cancers in developed countries
      with poor survival outcome in advanced stages of the disease due to its
      resistance to chemotherapy and other forms of treatment. New and alternative
      approaches are needed to overcome the tumour cells' capacity for survival and to
      drive the tumour towards cell death. Autophagy is a mechanism involved in the
      elimination of damaged cellular components through lysosomal degradation and is
      capable of inducing programmed cell death. The process has recently gained much
      interest in understanding the pathogenesis of CRC and its potential for treatment
      of the disease due to its role in host protection and anticancer activity. This
      review describes and illustrates the fundamental mechanisms of autophagy, its
      importance as a prognostic marker and the current approaches to harness its
      protective and anticancer activity in CRC therapy.

PMID- 25055794
TI  - Expression analysis of rice pathogenesis-related proteins involved in stress
      response and endophytic colonization properties of gfp-tagged Bacillus subtilis
      CB-R05.
AB  - Bacillus subtilis CB-R05, possessing antagonistic effects against several fungal
      pathogens, is a diazotrophic plant growth-promoting bacteria marked with the
      green fluorescent protein (gfp) gene. To confirm the expression level of the
      pathogenesis-related (PR) proteins in rice inoculated with CB-R05, the
      expressions of four pathogenesis-related (PR) proteins (PR2, PR6, PR15, and PR16)
      were examined in the rice leaves treated with wounding stress over a time period.
      The PR proteins were generally more strongly expressed in the rice leaves
      inoculated with CB-R05 compared with the untreated control. The marked gfp-tagged
      B. subtilis CB-R05 strain was inoculated onto the rice seedlings under axenic
      conditions. Under the confocal laser scanning microscope (CLSM), the gfp-tagged
      CB-R05 bacterial cells were observed to penetrate the rhizoplane, especially in
      the elongation and differentiation zones of the rice roots, and colonize the root
      intracellularly. The bacteria, 24 h after the gfp-tagged CB-R05 inoculation, were
      seen to penetrate into the cell wall, cortex, xylem, and concentrate mainly in
      the vascular bundle. Numerous bacteria were observed within the intercellular
      spaces, root cortical cells, and xylem vessels. Over time, these bacteria
      dispersed to the lateral root junctions and propagated slowly from the roots to
      the stems and leaves. The B. subtilis CB-R05 population in the rice root
      rhizosphere was also monitored. These results show a very widespread colonization
      of the B. subtilis CB-R05 in the rice rhizosphere. Further attempts are under way
      to investigate the competition between the CB-R05 bacteria and the fungal
      pathogen in vivo.

PMID- 25055795
TI  - Recovery of algal oil from marine green macro-algae Enteromorpha intestinalis by
      acidic-hydrothermal process.
AB  - In this study, the recovery of algal oil from Enteromorpha intestinalis based on
      an acidic-hydrothermal reaction was investigated. Overall, the algal oil yield
      after the acidic-hydrothermal reaction was increased under the conditions of high
      reaction temperature, high catalyst concentration, and long reaction time within
      the tested ranges. Significantly, catalyst concentration, compared with reaction
      temperature and time, less affected algal oil recovery. The optimal acidic
      hydrothermal reaction conditions for production of algal oil from E. intestinalis
      were as follows-200  degrees C reaction temperature, 2.92 % catalyst
      concentration, 54 min reaction time. Under these conditions, an 18.6 % algal oil
      yield was obtained. By increasing the combined severity factor, the algae oil
      recovery yield linearly increased.

PMID- 25055796
TI  - Diagnosing malaria infected cells at the single cell level using focal plane
      array Fourier transform infrared imaging spectroscopy.
AB  - New methods are needed to rapidly identify malaria parasites in blood smears. The
      coupling of a Focal Plane Array (FPA) infrared microscope system to a synchrotron
      light source at IRENI enables rapid molecular imaging at high spatial resolution.
      The technique, in combination with hyper-spectral processing, enables imaging and
      diagnosis of early stage malaria parasites at the single cell level in a blood
      smear. The method relies on the detection of distinct lipid signatures associated
      with the different stages of the malaria parasite and utilises resonant Mie
      extended multiplicative scatter correction to pre-process the spectra followed by
      full bandwidth image deconvolution to resolve the single cells. This work
      demonstrates the potential of focal plane technology to diagnose single cells in
      a blood smear. Brighter laboratory based infrared sources, optical refinements
      and higher sensitive detectors will soon see the emergence of focal plane array
      imaging in the clinical environment. 

PMID- 25055797
TI  - A patient diagnosed with BRAF-mutated non-small cell lung cancer and hairy cell
      leukemia: at last, which entity is really carrying the BRAF mutation?

PMID- 25055798
TI  - Emergency internal carotid artery stenting with platelet glycoprotein IIbIIIa
      antagonist coverage in a patient with essential thrombocytosis.

PMID- 25055799
TI  - UGT1A1 *6 polymorphism predicts outcome in elderly patients with relapsed or
      refractory diffuse large B-cell lymphoma treated with carboplatin, dexamethasone,
      etoposide and irinotecan.
AB  - The uridine diphosphate glucuronosyltransferase (UGT) gene 1A1*6 polymorphism,
      which affects irinotecan metabolism, has been associated with improved survival
      in lymphoma patients treated with of carboplatin, dexamethasone, etoposide and
      irinotecan (CDE-11). This study assessed the efficacy of CDE-11 relative to the
      UGT1A1*6 polymorphism in 27 elderly patients with relapsed or refractory diffuse
      large B-cell lymphoma who were ineligible for high-dose chemotherapy plus
      autologous stem cell transplantation. The 2-year survival rate after initial CDE
      11 treatment was significantly higher in patients with than without UGT1A1*6 (57%
      vs. 5%). The most common grade 4 adverse event in patients with the UGT1A1*6
      genotypes was neutropenia (88.9%), but there were no gastrointestinal adverse
      events or treatment-related deaths. Disease progression was the most frequent
      cause of death. CDE-11 was well tolerated and provided clinical benefit to
      elderly patients with relapsed or refractory diffuse large B-cell lymphoma. The
      response to CDE-11 likely correlated with UGT1A1*6 polymorphisms, but further
      prospective studies are warranted to optimize irinotecan-based chemotherapies
      relative to UGT1A1 polymorphism. 

PMID- 25055800
TI  - Signaling pathway genes for blood pressure, folate and cholesterol levels among
      hypertensives: an epistasis analysis.
AB  - Irregular atrial pressure, defective folate and cholesterol metabolism contribute
      to the pathogenesis of hypertension. However, little is known about the combined
      roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE)
      and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism
      and homeostasis. The objective of this study is to investigate the association of
      the MTHFR 677 C>T and 1298A>C, ACE insertion-deletion (I/D) and ApoE genetic
      polymorphisms with hypertension and to further explore the epistasis interactions
      that are involved in these mechanisms. A total of 594 subjects, including 348
      normotensive and 246 hypertensive ischemic stroke subjects were recruited. The
      MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the
      epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms
      demonstrated significant associations with susceptibility to hypertension in
      multiple logistic regression models, multifactor dimensionality reduction and a
      classification and regression tree. In addition, the logistic regression model
      demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and
      MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis
      study indicated significant association between the ApoE and MTHFR polymorphisms
      and hypertension. 

PMID- 25055801
TI  - Molecular surface of JZTX-V (beta-Theraphotoxin-Cj2a) interacting with voltage
      gated sodium channel subtype NaV1.4.
AB  - Voltage-gated sodium channels (VGSCs; NaV1.1-NaV1.9) have been proven to be
      critical in controlling the function of excitable cells, and human genetic
      evidence shows that aberrant function of these channels causes channelopathies,
      including epilepsy, arrhythmia, paralytic myotonia, and pain. The effects of
      peptide toxins, especially those isolated from spider venom, have shed light on
      the structure-function relationship of these channels. However, most of these
      toxins have not been analyzed in detail. In particular, the bioactive faces of
      these toxins have not been determined. Jingzhaotoxin (JZTX)-V (also known as beta
      theraphotoxin-Cj2a) is a 29-amino acid peptide toxin isolated from the venom of
      the spider Chilobrachys jingzhao. JZTX-V adopts an inhibitory cysteine knot (ICK)
      motif and has an inhibitory effect on voltage-gated sodium and potassium
      channels. Previous experiments have shown that JZTX-V has an inhibitory effect on
      TTX-S and TTX-R sodium currents on rat DRG cells with IC50 values of 27.6 and
      30.2 nM, respectively, and is able to shift the activation and inactivation
      curves to the depolarizing and the hyperpolarizing direction, respectively. Here,
      we show that JZTX-V has a much stronger inhibitory effect on NaV1.4, the isoform
      of voltage-gated sodium channels predominantly expressed in skeletal muscle
      cells, with an IC50 value of 5.12 nM, compared with IC50 values of 61.7-2700 nM
      for other heterologously expressed NaV1 subtypes. Furthermore, we investigated
      the bioactive surface of JZTX-V by alanine-scanning the effect of toxin on NaV1.4
      and demonstrate that the bioactive face of JZTX-V is composed of three
      hydrophobic (W5, M6, and W7) and two cationic (R20 and K22) residues. Our results
      establish that, consistent with previous assumptions, JZTX-V is a Janus-faced
      toxin which may be a useful tool for the further investigation of the structure
      and function of sodium channels. 

PMID- 25055803
TI  - Niacin fails to reduce vascular events in large randomised trial.

PMID- 25055802
TI  - Regulation of cry gene expression in Bacillus thuringiensis.
AB  - Bacillus thuringiensis differs from the closely related Bacillus cereus group
      species by its ability to produce crystalline inclusions. The production of these
      crystals mainly results from the expression of the cry genes, from the stability
      of their transcripts and from the synthesis, accumulation and crystallization of
      large amounts of insecticidal Cry proteins. This process normally coincides with
      sporulation and is regulated by various factors operating at the transcriptional,
      post-transcriptional, metabolic and post-translational levels. 

PMID- 25055804
TI  - Short-term changes of intraocular pressure after cervical interlaminar epidural
      injection: a pilot study.
AB  - BACKGROUND: Cervical epidural injection (CEI) is widely performed on patients
      with intervertebral disc herniation. The aim of the present study was to
      investigate the short-term effects of CEI on non-invasive intraocular pressure
      (IOP) measurements in subjects with normal eyes. METHODS: This prospective study
      enrolled 15 patients who were undergoing CEI at the C5/6 level with an
      interlaminar approach in the left lateral decubitus position. IOP was measured in
      both eyes by a rebound tonometer (Icare-PRO, Icare Finland Oy, Helsinki,
      Finland). A total volume of 14 ml (4 ml non-ionic contrast, a mixture of 0.2%
      lidocaine 1 ml and normal saline 4 ml for irrigation and a mixture of normal
      saline 4.5 ml with non-particulate betamethasone 2 mg) was injected with 1.0 ml
      s(-1). IOP was measured 5 min after the lateral decubitus position (T0,
      baseline), immediately after CEI (T1), and 1 min intervals for 5 min (T2-T6).
      RESULTS: The values of left and right baseline IOP (T0) were 18.9 (2.0) and 15.6
      (2.6) mm Hg, respectively. IOP of left and right eyes at T1 [26.6 (4.2) and 21.2
      (2.5) mm Hg, respectively] and T2 [26.2 (4.5) and 21.0 (2.8) mm Hg, respectively]
      were significantly higher compared with T0. These values immediately decreased at
      T3 and returned to baseline levels within 5 min after CEI. CONCLUSIONS: CEI
      resulted in an elevation of IOP of both eyes. However, the effects were transient
      only lasting a few minutes.

PMID- 25055805
TI  - Formal synthesis of (+)-3-epi-eupomatilone-6 and the 3,5-bis-epimer.
AB  - The formal synthesis of (+)-3-epi-eupomatilone-6 () and the 3,5-bis-epimer () has
      been accomplished. The key synthetic strategy involved the stereoselective
      construction of (3R,4S,5R)- and (3R,4S,5S)-trisubstituted gamma-butyrolactones
      and from (2R,3R)-2,3-dimethyl-4-pentenoic acid derivative , which was readily
      obtained via stereoselective conjugate addition of vinylmagnesium chloride to a
      chiral alpha,beta-unsaturated N-acyl oxazolidinone (Evans' auxiliary) followed by
      alpha-methylation. 

PMID- 25055806
TI  - A proposal for calculating the no-observed-adverse-effect level (NOAEL) for
      organic compounds responsible for liver toxicity based on their physicochemical
      properties.
AB  - OBJECTIVES: Both environmental and occupational exposure limits are based on the
      no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level
      (LOAEL) or benchmark dose (BMD) deriving from epidemiological and experimental
      studies. The aim of this study is to investigate to what extent the NOAEL values
      for organic compounds responsible for liver toxicity calculated based on their
      physicochemical properties could be used for calculating occupational exposure
      limits. MATERIAL AND METHODS: The distribution coefficients from air to the liver
      (log K(liver)) were calculated according to the Abraham solvation equation. NOAEL
      and LOAEL values for early effects in the liver were obtained from the literature
      data. The descriptors for Abraham's equation were found for 59 compounds, which
      were divided into 2 groups: "non-reactive" (alcohols, ketones, esters, ethers,
      aromatic and aliphatic hydrocarbons, amides) and "possibly reactive" (aldehydes,
      allyl compounds, amines, benzyl halides, halogenated hydrocarbons, acrylates).
      RESULTS: The correlation coefficients between log-log K and log NOAEL for non
      reactive and reactive compounds amounted to r = -0.8123 and r = -0.8045,
      respectively, and were statistically significant. It appears that the Abraham
      equation could be used to predict the NOAEL values for compounds lacking
      information concerning their liver toxicity. CONCLUSIONS: In view of the tendency
      to limit animal testing procedures, the method proposed in this paper can improve
      the practice of setting exposure guidelines for the unstudied compounds.

PMID- 25055807
TI  - [Development and future position of the Academy of German Urologists].
AB  - In order to do justice to the complex requirements of vocational training in
      urology, last year the Academy made great progress in further development. During
      the 65(th) annual congress of the Deutsche Gesellschaft fur Urologie (DGU, German
      Society of Urology) a multitude of Academy forums and Academy expert courses were
      offered again by the working groups. The Academy now provides four academy
      sections. After foundation of the junior academy and the team academy, the
      additional groups of patient academy and knowledge academy were also created. 

PMID- 25055808
TI  - [The demographic development in Germany : challenge and chances for urology].
AB  - Urology is affected by the demographic development in Germany more than any other
      medical discipline. Despite a relatively stable total population, by the year
      2040 there will be an absolute and relevant increase in urological diseases
      caused only by the demographic development in the population. This is
      particularly true for the increase in oncological treatment just in the field of
      the discipline of urology. Even now the current numbers for tumor development in
      Germany (RKI 2014) in the urological oncology segment of all tumor diseases show
      an increasing trend with more than 23 %. This significant increase in performance
      is in contrast to the age development of the specialists in this discipline. In
      total but especially due to the significantly over-aged specialist medical
      profession in urology, this leads to a substantial bottleneck of specialists in
      the discipline of urology. This deficiency of personnel resources in urology is
      aggravated by the requirements of Generation Y for a well-adjusted work-life
      balance and the associated feminization of the medical profession. This requires
      intelligent strategies for. 

PMID- 25055809
TI  - Dissociable cortico-striatal connectivity abnormalities in major depression in
      response to monetary gains and penalties.
AB  - BACKGROUND: Individuals with major depressive disorder (MDD) are characterized by
      maladaptive responses to both positive and negative outcomes, which have been
      linked to localized abnormal activations in cortical and striatal brain regions.
      However, the exact neural circuitry implicated in such abnormalities remains
      largely unexplored. METHOD: In this study 26 unmedicated adults with MDD and 29
      matched healthy controls (HCs) completed a monetary incentive delay task during
      functional magnetic resonance imaging (fMRI). Psychophysiological interaction
      (PPI) analyses probed group differences in connectivity separately in response to
      positive and negative outcomes (i.e. monetary gains and penalties). RESULTS:
      Relative to HCs, MDD subjects displayed decreased connectivity between the
      caudate and dorsal anterior cingulate cortex (dACC) in response to monetary
      gains, yet increased connectivity between the caudate and a different, more
      rostral, dACC subregion in response to monetary penalties. Moreover, exploratory
      analyses of 14 MDD patients who completed a 12-week, double-blind, placebo
      controlled clinical trial after the baseline fMRI scans indicated that a more
      normative pattern of cortico-striatal connectivity pre-treatment was associated
      with greater improvement in symptoms 12 weeks later. CONCLUSIONS: These results
      identify the caudate as a region with dissociable incentive-dependent dACC
      connectivity abnormalities in MDD, and provide initial evidence that cortico
      striatal circuitry may play a role in MDD treatment response. Given the role of
      cortico-striatal circuitry in encoding action-outcome contingencies, such
      dysregulated connectivity may relate to the prominent disruptions in goal
      directed behavior that characterize MDD.

PMID- 25055811
TI  - Ethical considerations in design of a study to evaluate a US Food and Drug
      Administration-approved indication: antivenom versus placebo for copperhead
      envenomation.
AB  - BACKGROUND: In 2000, the US Food and Drug Administration approved CroFab((r))
      Crotalidae Polyvalent Immune Fab, ovine (FabAV), which had received orphan drug
      designation, for use in patients with minimal to moderate North American
      crotaline envenomations including copperhead snakes. As existing evidence on the
      effectiveness of FabAV for this indication is limited, wide practice variation in
      its use exists. In order to provide more definitive clinical evidence as to the
      role of this treatment, a new randomized, placebo-controlled trial of FabAV
      specifically for copperhead bites was initiated. PURPOSE: In light of the
      existing US Food and Drug Administration approval, ethical considerations of
      participation in this trial have been raised. We discuss the ethical principles
      pertinent to this randomized, placebo-controlled trial with placebo arm. We apply
      an accepted framework for ethical research to this trial. Due to the evidence gap
      in the literature, wide-ranging treatment recommendations by medical experts, and
      broad practice variation, clinical equipoise exists in the treatment of
      copperhead envenomation with FabAV. The impact of this clinical equipoise on the
      value and scientific validity of the trial is discussed. The trial's risk-benefit
      ratio is also considered. Potential risks to the patients are minimized as the
      protocol includes a plan for rescue therapy in the event that patients progress
      to severe envenomation symptoms. Overall, risks are further minimized by the
      inclusion of an interim analysis with stopping rules based on demonstrated
      efficacy should the therapy clearly prove to be beneficial. CONCLUSION: Although
      a post-marketing clinical study of this nature is unusual for an approved
      indication, this trial adheres to all ethical preconditions found in existing
      guidelines for clinical research involving human subjects.

PMID- 25055810
TI  - Definitions and potential health benefits of the Mediterranean diet: views from
      experts around the world.
AB  - The Mediterranean diet has been linked to a number of health benefits, including
      reduced mortality risk and lower incidence of cardiovascular disease. Definitions
      of the Mediterranean diet vary across some settings, and scores are increasingly
      being employed to define Mediterranean diet adherence in epidemiological studies.
      Some components of the Mediterranean diet overlap with other healthy dietary
      patterns, whereas other aspects are unique to the Mediterranean diet. In this
      forum article, we asked clinicians and researchers with an interest in the effect
      of diet on health to describe what constitutes a Mediterranean diet in different
      geographical settings, and how we can study the health benefits of this dietary
      pattern. 

PMID- 25055812
TI  - Site-specific predictors of successful recruitment to a perinatal clinical trial.
AB  - BACKGROUND: With large collaborations needed to reach sample size requirements
      for relatively rare events, a major challenge for multi-centre clinical trials is
      efficiency of recruitment at individual sites. We used data from an
      international, multi-centre, randomised trial of preterm prelabour rupture of
      membranes to assess any impact on recruitment following the introduction of a new
      Clinical Trial Agreement and to identify site-specific predictors of recruitment
      to the trial for the purpose of targeting future recruitment sites and
      strategies. METHODS: The outcome measure was recruitment rate per 10,000 births,
      and according to this, an average recruitment rate was determined. Factors that
      were considered potentially predictive of recruitment above the average rate were
      classified according to three broad themes: 'ethics and regulatory requirements',
      'characteristics of site investigators' and the 'research culture' at the
      collaborating site. Data were analysed using contingency tables and logistic
      regression modelling. RESULTS: At 31 January 2009, following the introduction of
      the Clinical Trial Agreement, 39 centres had obtained ethics approval to commence
      recruitment, and 38 centres had enrolled at least one woman. Time to first
      recruit ranged from 25 days to 584 days. Recruitment rates ranged from 0.18 to
      6.0 per 10,000 births (mean 1.71/10,000 births) per month. Factors most
      associated with above-average recruitment rate were the following: implementation
      of a clearly defined 'system' of recruitment, engagement of other staff, time
      from ethics approval to first recruit and provision of a dedicated trial
      coordinator. CONCLUSION: A delay of greater than 3 months in approval of the new
      Clinical Trial Agreement had an effect which extended into the third year of the
      trial. Characteristics that were indicative of the presence of a 'system' were
      the best predictors of recruitment. It may be more effective to limit recruitment
      sites and focus resources on those sites where investigators are engaged with
      trial processes and have adequate resources and structures to support them.

PMID- 25055813
TI  - Hybrid coronary revascularization: the future of coronary artery bypass surgery
      or an unfulfilled promise?

PMID- 25055814
TI  - Practice patterns and clinical outcomes after hybrid coronary revascularization
      in the United States: an analysis from the society of thoracic surgeons adult
      cardiac database.
AB  - BACKGROUND: Hybrid coronary revascularization (HCR) involves a combination of
      surgical and percutaneous techniques, which in selected patients may present an
      alternative to conventional coronary artery bypass grafting (CABG). METHODS AND
      RESULTS: Patients were included who underwent HCR (staged/concurrent) or isolated
      CABG in the Society of Thoracic Surgeons Adult Cardiac Surgery Database (July
      2011 to March 2013). HCR represented 0.48% (n=950; staged=809, concurrent=141) of
      the total CABG volume (n=198,622) during the study period, and was performed in
      one-third of participating centers (n=361). Patients who underwent HCR had higher
      cardiovascular risk profiles in comparison with patients undergoing CABG. In
      comparison with CABG, median sternotomy (98.5% for CABG, 61.1% for staged HCR,
      and 52.5% for concurrent HCR), direct vision harvesting (98.9%, 66.0%, and 68.1%)
      and cardiopulmonary bypass (83.4%, 45%, and 36.9%) were less frequently used for
      staged and concurrent HCR, whereas robotic assistance (0.7%, 33.0%, and 30.5%)
      was more common. After adjustment, no differences were observed for the composite
      of in-hospital mortality and major morbidity (odds ratio, 0.93; 95% confidence
      interval, 0.75-1.16; P=0.53 for staged HCR, and odds ratio, 0.94; 95% confidence
      interval, 0.56-1.56; P=0.80 for concurrent HCR in comparison with CABG). There
      was no statistically significant association between operative mortality and
      either treatment group (odds ratio, 0.74; 95% confidence interval, 0.42-1.30;
      P=0.29 for staged HCR, and odds ratio, 2.26; 95% confidence interval, 0.99-5.17;
      P=0.053 for concurrent HCR in comparison with CABG). CONCLUSION: HCR, either as a
      staged or concurrent procedure, is performed in one-third of US hospitals and is
      reserved for a highly selected patient population. Although HCR may appear to be
      an equally safe alternative for CABG surgery, further randomized study is
      warranted.

PMID- 25055815
TI  - Too much of a good thing: resource provisioning alters infectious disease
      dynamics in wildlife.
AB  - Provisioning of abundant food resources in human-altered landscapes can have
      profound effects on wildlife ecology, with important implications for pathogen
      transmission. While empirical studies have quantified the effects of provisioning
      on host behaviour and immunology, the net interactive effect of these components
      on host-pathogen dynamics is unknown. We use simple compartmental models to
      investigate how provisioning-induced changes to host demography, contact
      behaviour and immune defence influence pathogen invasion and persistence. We show
      that pathogen invasion success and equilibrium prevalence depend critically on
      how provisioning affects host immune defence and that moderate levels of
      provisioning can lead to drastically different outcomes of pathogen extinction or
      maximizing prevalence. These results highlight the need for further empirical
      studies to fully understand how provisioning affects pathogen transmission in
      urbanized environments. 

PMID- 25055816
TI  - Ungulate saliva inhibits a grass-endophyte mutualism.
AB  - Fungal endophytes modify plant-herbivore interactions by producing toxic
      alkaloids that deter herbivory. However, studies have neglected the direct
      effects herbivores may have on endophytes. Antifungal properties and signalling
      effectors in herbivore saliva suggest that evolutionary pressures may select for
      animals that mitigate the effects of endophyte-produced alkaloids. Here, we
      tested whether saliva of moose (Alces alces) and European reindeer (Rangifer
      tarandus) reduced hyphal elongation and production of ergot alkaloids by the
      foliar endophyte Epichloe festucae associated with the globally distributed red
      fescue Festuca rubra. Both moose and reindeer saliva reduced the growth of
      isolated endophyte hyphae when compared with a treatment of distilled water.
      Induction of the highly toxic alkaloid ergovaline was also inhibited in plants
      from the core of F. rubra's distribution when treated with moose saliva following
      simulated grazing. In genotypes from the southern limit of the species'
      distribution, ergovaline was constitutively expressed, as predicted where growth
      is environmentally limited. Our results now present the first evidence, to our
      knowledge, that ungulate saliva can combat plant defences produced by a grass
      endophyte mutualism. 

PMID- 25055817
TI  - Heroes in endocrinology: Nobel Prizes.
AB  - The Nobel Prize in Physiology or Medicine was first awarded in 1901. Since then,
      the Nobel Prizes in Physiology or Medicine, Chemistry and Physics have been
      awarded to at least 33 distinguished researchers who were directly or indirectly
      involved in research into the field of endocrinology. This paper reflects on the
      life histories, careers and achievements of 11 of them: Frederick G Banting,
      Roger Guillemin, Philip S Hench, Bernardo A Houssay, Edward C Kendall, E Theodor
      Kocher, John J R Macleod, Tadeus Reichstein, Andrew V Schally, Earl W Sutherland,
      Jr and Rosalyn Yalow. All were eminent scientists, distinguished lecturers and
      winners of many prizes and awards. 

PMID- 25055818
TI  - Systemic effects of intratympanic dexamethasone therapy.
AB  - OBJECTIVE: The study aimed to assess the possible systemic effects of
      intratympanic dexamethasone (IT-Dex) on the hypothalamic-pituitary-adrenal (HPA)
      axis, inflammation, and bone metabolism. DESIGN: A prospective cohort study
      including 30 adult patients of a tertiary referral ENT clinic treated with 9.6 mg
      IT-Dex over a period of 10 days was carried out. METHODS: Effects on plasma and
      salivary cortisol concentrations (basal and after low-dose (1 MUg) ACTH
      stimulation), peripheral white blood cell count, and biomarkers for bone turnover
      were measured before (day 0) and after IT-Dex (day 16). Additional measurements
      for bone turnover were performed 5 months after therapy. Clinical information and
      medication with possible dexamethasone interaction were recorded. RESULTS: IT-Dex
      was well tolerated, and no effect was detected on the HPA axis (stimulated plasma
      and salivary cortisol concentration on day 0: 758+/-184 and 44.5+/-22.0 nmol/l;
      day 16: 718+/-154 and 39.8+/-12.4 nmol/l; P=0.58 and 0.24 respectively).
      Concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP)
      did not differ after dexamethasone (OC on days 0 and 16 respectively: 24.1+/-10.5
      and 23.6+/-8.8 MUg/l; BSAP on day 0, 16, and after 5 months respectively: 11.5+/
      4.2, 10.3+/-3.4, and 12.6+/-5.06 MUg/l); similarly, there was no difference in
      the peripheral white blood cell count (5.7*10(12)/l and 6.1*10(12)/l on days 0
      and 16 respectively). CONCLUSIONS: IT-Dex therapy did not interfere with
      endogenous cortisol secretion or bone metabolism.

PMID- 25055819
TI  - Seizure reduction in a low-grade glioma: more than a beneficial side effect of
      temozolomide.
AB  - BACKGROUND: Seizures are a common symptom in patients with low-grade glioma
      (LGG), negatively influencing quality of life, if uncontrolled. Besides
      antiepileptic drugs, antitumour treatment might contribute to a reduction in
      seizure frequency. The aim of this study was to determine the effect of
      temozolomide (TMZ) chemotherapy on seizure frequency, to identify factors
      associated with post-treatment seizure reduction and to analyse the prognostic
      value of seizure reduction for survival. METHODS: We retrospectively reviewed
      adult patients with supratentorial LGG and epilepsy who received chemotherapy
      with TMZ as initial treatment or for progressive disease in two hospitals (VUmc
      Amsterdam; MCH The Hague) between 2002 and 2012. RESULTS: We identified 104
      patients with LGG with epilepsy who had received TMZ. Uncontrolled epilepsy in
      the 3 months preceding chemotherapy was present in 66 of 104 (63.5%) patients. A
      >= 50% reduction in seizure frequency after 6 months occurred in 29 of 66 (43.9%)
      patients. Focal symptoms at presentation (OR 6.55; 95% CI 1.45 to 32.77; p =
      0.015) appeared to be positively associated with seizure reduction. Seizure
      reduction was an independent prognostic factor for progression-free survival (HR
      0.32; 95% CI 0.15 to 0.66; p = 0.002) and overall survival (HR 0.33; 95% CI 0.14
      to 0.79; p = 0.013), along with a histological diagnosis of oligodendroglioma (HR
      0.38; 95% CI 0.17 to 0.86; p = 0.021). Objective responses on MRI were similar
      for patients with and without seizure reduction. CONCLUSIONS: TMZ may contribute
      to an important reduction in seizure frequency in patients with LGG. Seizure
      reduction following TMZ treatment has prognostic significance and may serve as an
      important clinical outcome measure in patients with LGG.

PMID- 25055821
TI  - Effect of electroacupuncture versus prucalopride for severe chronic constipation:
      protocol of a multi-centre, non-inferiority, randomised controlled trial.
AB  - BACKGROUND: Acupuncture is safe and may be effective for severe chronic
      constipation. The World Gastroenterology Organisation recommends prucalopride for
      patients for whom previous laxative use failed to provide satisfactory relief.
      METHODS/DESIGN: In this prospective, multi-centre, randomised controlled trial,
      five hundred sixty patients with severe chronic constipation (two or less
      spontaneous complete bowel movements per week) from 14 centres will be randomised
      to receive either electroacupuncture or prucalopride. Participants in the
      electroacupuncture group will receive electroacupuncture for eight weeks, while
      participants in the control group will take prucalopride (2 mg once daily) for 32
      weeks. The primary outcome measure is the proportion of patients having >= 3
      spontaneous, complete bowel movements per week, averaged over week three to
      eight. The secondary outcome measures include eight items, including the
      proportion of patients having >= 3 spontaneous, complete bowel movements per week
      averaged over week 9-32, the proportion of patients with one or more increases in
      spontaneous, complete bowel movements per week from baseline, mean Bristol Stool
      Scale, etc. Statistical analysis will include the CMH test, nonparametric tests
      and t tests. DISCUSSION: We aimed to compare the effect of electroacupuncture
      versus prucalopride for severe chronic constipation. The limitation of this study
      is that participants and acupuncturists will not be blinded. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT 02047045.

PMID- 25055822
TI  - Visualization of nucleotide substitutions in the (micro)transcriptome.
AB  - BACKGROUND: RNA-related applications of the next-generation sequencing (NGS)
      technologies require context-specific interpretations: e.g., sequence mismatches
      may indicate sites of RNA editing, or uneven read coverage often points to mature
      form of microRNA. Existing visualization tools traditionally show RNA molecules
      in two dimensions, with their base pairing and the resulting secondary structure.
      However, it is not straightforward to combine a linear NGS data display with the
      2-D RNA depictions. RESULTS: We present a novel approach for interactive
      representation of nucleotide substitutions and modifications in the transcribed
      genome. With the focus on RNA secondary structure in the context of NGS data, it
      provides intuitive visualization of genomic environment, sequence reads,
      nucleotide polymorphisms and editing events integrated with the structural and
      functional elements of both coding and non-coding RNA molecules. Using our
      approach we present and discuss examples and general trends of polymorphisms and
      editing in the context of the secondary structure of microRNAs. As expected, most
      of the substitutions comprised A to G and C to T events, consistent with typical
      RNA editing patterns. However, we did not observe prevalence of editing in double
      stranded regions of the microRNA stem-loop. We describe novel prominent editing
      event candidates, observed across several small RNA libraries of Drosophila
      melanogaster. CONCLUSIONS: In contrast to the existing general tools for NGS data
      visualization, the power of our approach is not only in the display of read
      alignments and their counts, but the integration of RNA secondary structure,
      sequencing depth, and rates/patterns of editing or other modifications. It
      provides a comprehensive picture, important for large-scale studies and detailed
      analyses, helping to gain insight into the intricate relationships between
      different events in RNA biogenesis.

PMID- 25055823
TI  - Cerebral salt-wasting syndrome due to hemorrhagic brain infarction: a case
      report.
AB  - INTRODUCTION: Cerebral salt-wasting syndrome is a condition featuring
      hyponatremia and dehydration caused by head injury, operation on the brain,
      subarachnoid hemorrhage, brain tumor and so on. However, there are a few reports
      of cerebral salt-wasting syndrome caused by cerebral infarction. We describe a
      patient with cerebral infarction who developed cerebral salt-wasting syndrome in
      the course of hemorrhagic transformation. CASE PRESENTATION: A 79-year-old
      Japanese woman with hypertension and arrhythmia was admitted to our hospital for
      mild consciousness disturbance, conjugate deviation to right, left unilateral
      spatial neglect and left hemiparesis. Magnetic resonance imaging revealed a broad
      ischemic change in right middle cerebral arterial territory. She was diagnosed as
      cardiogenic cerebral embolism because atrial fibrillation was detected on
      electrocardiogram on admission. She showed hyponatremia accompanied by polyuria
      complicated at the same time with the development of hemorrhagic transformation
      on day 14 after admission. Based on her hypovolemic hyponatremia, she was
      evaluated as not having syndrome of inappropriate secretion of antidiuretic
      hormone but cerebral salt-wasting syndrome. She fortunately recovered with proper
      fluid replacement and electrolyte management. CONCLUSIONS: This is a rare case of
      cerebral infarction and cerebral salt-wasting syndrome in the course of
      hemorrhagic transformation. It may be difficult to distinguish cerebral salt
      wasting syndrome from syndrome of inappropriate antidiuretic hormone, however, an
      accurate assessment is needed to reveal the diagnosis of cerebral salt-wasting
      syndrome because the recommended fluid management is opposite in the two
      conditions.

PMID- 25055824
TI  - Epidermal growth factor-induced proliferation of collecting duct cells from Oak
      Ridge polycystic kidney mice involves activation of Na+/H+ exchanger.
AB  - Epidermal growth factor (EGF) is linked to the pathogenesis of polycystic kidney
      disease (PKD). We explored signaling pathways activated by EGF in orpk cilia (-)
      collecting duct cell line derived from a mouse model of PKD (hypomorph of the
      Tg737/Ift88 gene) with severely stunted cilia, and in a control orpk cilia (+)
      cell line with normal cilia. RT-PCR demonstrated mRNAs for EGF receptor subunits
      ErbB1, ErbB2, ErbB3, ErbB4, and mRNAs for Na(+)/H(+) exchangers (NHE), NHE-1, NHE
      2, NHE-3, NHE-4, and NHE-5 in both cell lines. EGF stimulated proton efflux in
      both cell lines. This effect was significantly attenuated by MIA, 5-(n-methyl-N
      isobutyl) amiloride, a selective inhibitor of NHE-1 and NHE-2, and orpk cilia (-)
      cells were more sensitive to MIA than control cells (P < 0.01). EGF significantly
      induced extracellular signal-regulated kinase (ERK) phosphorylation in both cilia
      (+) and cilia (-) cells (63.3 and 123.6%, respectively), but the effect was more
      pronounced in orpk cilia (-) cells (P < 0.01). MIA significantly attenuated EGF
      induced ERK phosphorylation only in orpk cilia (-) cells (P < 0.01). EGF
      increased proliferation of orpk cilia (+) cells and orpk cilia (-) cells,
      respectively, and MIA at 1-5 MUM attenuated EGF-induced proliferation in orpk
      cilia (-) cells without affecting proliferation of orpk cilia (+) cells. EGF
      induced proliferation of both cell lines was significantly decreased by the EGFR
      tyrosine kinase inhibitor AG1478 and MEK inhibitor PD98059. These results suggest
      that EGF exerts mitogenic effects in the orpk cilia (-) cells via activation of
      growth-associated amiloride-sensitive NHEs and ERK. 

PMID- 25055825
TI  - Platelet-derived growth factor receptor-alpha-positive cells and not smooth
      muscle cells mediate purinergic hyperpolarization in murine colonic muscles.
AB  - Enteric inhibitory neurotransmission is an important feature of the neural
      regulation of gastrointestinal motility. Purinergic neurotransmission, via P2Y1
      receptors, mediates one phase of inhibitory neural control. For decades, ATP has
      been assumed to be the purinergic neurotransmitter and smooth muscle cells (SMCs)
      have been considered the primary targets for inhibitory neurotransmission. Recent
      experiments have cast doubt on both of these assumptions and suggested that
      another cell type, platelet-derived growth factor receptor-alpha-positive
      (PDGFRalpha(+)) cells, is the target for purinergic neurotransmission. We
      compared responses of PDGFRalpha(+) cells and SMCs to several purine compounds to
      determine if these cells responded in a manner consistent with enteric inhibitory
      neurotransmission. ATP hyperpolarized PDGFRalpha(+) cells but depolarized SMCs.
      Only part of the ATP response in PDGFRalpha(+) cells was blocked by MRS 2500, a
      P2Y1 antagonist. ADP, MRS 2365, beta-NAD, and adenosine 5-diphosphate-ribose,
      P2Y1 agonists, hyperpolarized PDGFRalpha(+) cells, and these responses were
      blocked by MRS 2500. Adenosine 5-diphosphate-ribose was more potent in eliciting
      hyperpolarization responses than beta-NAD. P2Y1 agonists failed to elicit
      responses in SMCs. Small hyperpolarization responses were elicited in SMCs by a
      small-conductance Ca(2+)-activated K(+) channel agonist, cyclohexyl-[2-(3,5
      dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, consistent with the low
      expression and current density of small-conductance Ca(2+)-activated K(+)
      channels in these cells. Large-amplitude hyperpolarization responses, elicited in
      PDGFRalpha(+) cells, but not SMCs, by P2Y1 agonists are consistent with the
      generation of inhibitory junction potentials in intact muscles in response to
      purinergic neurotransmission. The responses of PDGFRalpha(+) cells and SMCs to
      purines suggest that SMCs are unlikely targets for purinergic neurotransmission
      in colonic muscles. 

PMID- 25055826
TI  - Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat
      brain and vasculature.
AB  - Mammals have circadian variation in blood pressure, heart rate, vascular tone,
      thrombotic tendency, and cerebral blood flow (CBF). These changes may be in part
      orchestrated by circadian variation in clock gene expression within cells
      comprising the vasculature that modulate blood flow (e.g., fibroblasts, cerebral
      vascular smooth muscle cells, astrocytes, and endothelial cells). However, the
      downstream mechanisms that underlie circadian changes in blood flow are unknown.
      Cytochrome P450 epoxygenases (Cyp4x1 and Cyp2c11) are expressed in the brain and
      vasculature and metabolize arachidonic acid (AA) to form epoxyeicosatrienoic
      acids (EETs). EETs are released from astrocytes, neurons, and vascular
      endothelial cells and act as potent vasodilators, increasing blood flow. EETs
      released in response to increases in neural activity evoke a corresponding
      increase in blood flow known as the functional hyperemic response. We examine the
      hypothesis that Cyp2c11 and Cyp4x1 expression and EETs production vary in a
      circadian manner in the rat brain and cerebral vasculature. RT-PCR revealed
      circadian/diurnal expression of clock and clock-controlled genes as well as
      Cyp4x1 and Cyp2c11, within the rat hippocampus, middle cerebral artery, inferior
      vena cava, hippocampal astrocytes and rat brain microvascular endothelial cells.
      Astrocyte and endothelial cell culture experiments revealed rhythmic variation in
      Cyp4x1 and Cyp2c11 gene and protein expression with a 12-h period and parallel
      rhythmic production of EETs. Our data suggest there is circadian regulation of
      Cyp4x1 and Cyp2c11 gene expression. Such rhythmic EETs production may contribute
      to circadian changes in blood flow and alter risk of adverse cardiovascular
      events throughout the day. 

PMID- 25055828
TI  - Suppression of inflammatory responses of human gingival fibroblasts by gingipains
      from Porphyromonas gingivalis.
AB  - The interaction between human gingival fibroblasts (HGFs) and Porphyromonas
      gingivalis plays an important role in the development and progression of
      periodontitis. Porphyromonas gingivalis possesses several virulence factors,
      including cysteine proteases, the arginine-specific (Rgp) and lysine-specific
      (Kgp) gingipains. Studying the mechanisms that P. gingivalis, and its derived
      virulence, use to propagate and interact with host cells will increase the
      understanding of the development and progression of periodontitis. In this study,
      we aimed to elucidate how P. gingivalis influences the inflammatory events in
      HGFs regarding transforming growth factor-beta1 (TGF-beta1 ), CXCL8, secretory
      leucocyte protease inhibitor (SLPI), c-Jun and indoleamine 2,3-dioxygenase (IDO).
      HGFs were inoculated for 6 and 24 h with the wild-type strains ATCC 33277 and
      W50, two gingipain-mutants of W50 and heat-killed ATCC 33277. The P. gingivalis
      regulated CXCL8 and TGF-beta1 in HGFs, and the kgp mutant gave significantly
      higher immune response with increased CXCL8 (P < 0.001) and low levels of TGF
      beta1 . We show that HGFs express and secrete SLPI, which was significantly
      suppressed by P. gingivalis (P < 0.05). This suggests that by antagonizing SLPI,
      P. gingivalis contributes to the tissue destruction associated with
      periodontitis. Furthermore, we found that P. gingivalis inhibits the expression
      of the antimicrobial IDO, as well as upregulating c-Jun (P < 0.05). In
      conclusion, P. gingivalis both triggers and suppresses the immune response in
      HGFs. Consequently, we suggest that the pathogenic effects of P. gingivalis, and
      especially the activity of the gingipains on the inflammatory and immune response
      of HGFs, are crucial in periodontitis.

PMID- 25055829
TI  - Dabigatran: how the drug company withheld important analyses.

PMID- 25055830
TI  - The trouble with dabigatran.

PMID- 25055831
TI  - Concerns over data in key dabigatran trial.

PMID- 25055832
TI  - Route-dependent switch between hierarchical and egalitarian strategies in pigeon
      flocks.
AB  - The mechanisms that underlie fascinating inter-individual interactions among
      animal groups have attracted increasing attention from biologists, physicists,
      and system scientists. There are two well-known types of interaction patterns:
      hierarchical and egalitarian. In the former type, individuals follow their
      leaders, whereas they follow their neighbors in the latter. Using high-resolution
      spatiotemporal data derived from the free flights of a flock of pigeons, we show
      that pigeon flocks actually adopt a mode that switches between the two
      aforementioned strategies. To determine its flight direction, each pigeon tends
      to follow the average of its neighbors while moving along a smooth trajectory,
      whereas it switches to follow its leaders when sudden turns or zigzags occur. By
      contrast, when deciding how fast to fly, each pigeon synthesizes the average
      velocity of its neighbors. This switching mechanism is promising for possible
      industrial applications in multi-robot system coordination, unmanned vehicle
      formation control, and other areas. 

PMID- 25055833
TI  - Dynamic parent-of-origin effects on small interfering RNA expression in the
      developing maize endosperm.
AB  - BACKGROUND: In angiosperms, the endosperm plays a crucial placenta-like role in
      that not only is it necessary for nurturing the embryo, but also regulating
      embryogenesis through complicated genetic and epigenetic interactions with other
      seed compartments and is the primary tissue in which genomic imprinting occurs.
      RESULTS: We observed a gradual increase of paternal siRNA expression in the early
      stages of kernels and an expected 2:1 maternal to paternal ratio in 7-DAP
      endosperm via sequencing of small interfering RNA (siRNA) transcriptomes in
      developing kernels (0, 3 and 5 days after pollination (DAP)) and endosperms (7,
      10 and 15 DAP) from the maize B73 and Mo17 reciprocal crosses. Additionally, 460
      imprinted siRNA loci were identified in the endosperm, with the majority
      (456/460, 99.1%) being maternally expressed at 10 DAP. Moreover, 13 out of 29
      imprinted genes harbored imprinted siRNA loci within their 2-kb flanking regions,
      a significant higher frequency than expected based on simulation analysis.
      Additionally, gene ontology terms of "response to auxin stimulus", "response to
      brassinosteroid stimulus" and "regulation of gene expression" were enriched with
      genes harboring 10-DAP specific siRNAs, whereas those of "nutrient reservoir
      activity", "protein localization to vacuole" and "secondary metabolite
      biosynthetic process" were enriched with genes harboring 15-DAP specific siRNAs.
      CONCLUSIONS: A subset of siRNAs subjected to imprinted expression pattern in
      maize developing endosperm, and they are likely correlated with certain imprinted
      gene expression. Additionally, siRNAs might influence nutrient uptake and
      allocation processes during maize endosperm development.

PMID- 25055834
TI  - Oral anticoagulation with rivaroxaban during pregnancy: a case report.

PMID- 25055835
TI  - Predicting the performance of motor imagery in stroke patients: multivariate
      pattern analysis of functional MRI data.
AB  - BACKGROUND: In a brain-computer interface for stroke rehabilitation, motor
      imagery is a preferred means for providing a gateway to an effector action or
      behavior. However, stroke patients often exhibit failure to comply with motor
      imagery, and therefore their motor imagery performance is highly variable.
      OBJECTIVE: We sought to identify motor cortical areas responsible for motor
      imagery performance in stroke patients, specifically by using a multivariate
      pattern analysis of functional magnetic resonance imaging data. METHODS: We
      adopted an imaginary finger tapping task in which motor imagery performance could
      be monitored for 12 chronic stroke patients with subcortical infarcts and 12 age-
      and sex-matched healthy controls. We identified the typical activation pattern
      elicited for motor imagery in healthy controls, as computed over the voxels
      within each searchlight in the motor cortex. Then we measured the similarity of
      each individual's activation pattern to the typical activation pattern. RESULTS:
      In terms of activation levels, the stroke patients showed no activation in the
      ipsilesional primary motor cortex (M1); in terms of activation patterns, they
      showed lower similarity to the typical activation pattern in the area than the
      healthy controls. Furthermore, the stroke patients were better able to perform
      motor imagery if their activation patterns in the bilateral supplementary motor
      areas and ipsilesional M1 were close to the typical activation pattern.
      CONCLUSIONS: These findings suggest functional roles of the motor cortical areas
      for compliance with motor imagery in stroke, which can be applied to the
      implementation of motor imagery-based brain-computer interface for stroke
      rehabilitation.

PMID- 25055836
TI  - Rehabilitative training promotes rapid motor recovery but delayed motor map
      reorganization in a rat cortical ischemic infarct model.
AB  - BACKGROUND: In preclinical stroke models, improvement in motor performance is
      associated with reorganization of cortical motor maps. However, the temporal
      relationship between performance gains and map plasticity is not clear.
      OBJECTIVE: This study was designed to assess the effects of rehabilitative
      training on the temporal dynamics of behavioral and neurophysiological endpoints
      in a rat model of focal cortical infarct. METHODS: Eight days after an ischemic
      infarct in primary motor cortex, adult rats received either rehabilitative
      training or were allowed to recover spontaneously. Motor performance and movement
      quality of the paretic forelimb was assessed on a skilled reach task.
      Intracortical microstimulation mapping procedures were conducted to assess the
      topography of spared forelimb representations either at the end of training (post
      lesion day 18) or at the end of a 3-week follow-up period (post-lesion day 38).
      RESULTS: Rats receiving rehabilitative training demonstrated more rapid
      improvement in motor performance and movement quality during the training period
      that persisted through the follow-up period. Motor maps in both groups were
      unusually small on post-lesion day 18. On post-lesion day 38, forelimb motor maps
      in the rehabilitative training group were significantly enlarged compared with
      the no-rehab group, and within the range of normal maps. CONCLUSIONS: Postinfarct
      rehabilitative training rapidly improves motor performance and movement quality
      after an ischemic infarct in motor cortex. However, training-induced motor
      improvements are not reflected in spared motor maps until substantially later,
      suggesting that early motor training after stroke can help shape the evolving
      poststroke neural network.

PMID- 25055837
TI  - GABA levels are decreased after stroke and GABA changes during rehabilitation
      correlate with motor improvement.
AB  - BACKGROUND AND OBJECTIVE: gamma-Aminobutyric acid (GABA) is the dominant
      inhibitory neurotransmitter in the brain and is important in motor learning. We
      aimed to measure GABA content in primary motor cortex poststroke (using GABA
      edited magnetic resonance spectroscopy [MRS]) and in relation to motor recovery
      during 2 weeks of constraint-induced movement therapy (CIMT). METHODS: Twenty-one
      patients (3-12 months poststroke) and 20 healthy subjects were recruited.
      Magnetic resonance imaging structural T1 and GABA-edited MRS were performed at
      baseline and after CIMT, and once in healthy subjects. GABA:creatine (GABA:Cr)
      ratio was measured by GABA-edited MRS. Motor function was measured using Wolf
      Motor Function Test (WMFT). RESULTS: Baseline comparison between stroke patients
      (n = 19) and healthy subjects showed a significantly lower GABA:Cr ratio in
      stroke patients (P < .001) even after correcting for gray matter content in the
      voxel (P < .01) and when expressing GABA relative to N-acetylaspartic acid (NAA;
      P = .03). After 2 weeks of CIMT patients improved significantly on WMFT, but no
      consistent change across the group was observed for the GABA:Cr ratio (n = 17).
      However, the extent of improvement on WMFT correlated significantly with the
      magnitude of GABA:Cr changes (P < .01), with decreases in GABA:Cr ratio being
      associated with better improvements in motor function. CONCLUSIONS: In patients 3
      to 12 months poststroke, GABA levels are lower in the primary motor cortex than
      in healthy subjects. The observed association between GABA and recovery warrants
      further studies on the potential use of GABA MRS as a biomarker in poststroke
      recovery.

PMID- 25055838
TI  - Unilateral and bilateral upper-limb training interventions after stroke have
      similar effects on bimanual coupling strength.
AB  - BACKGROUND: Bilateral training in poststroke upper-limb rehabilitation is based
      on the premise that simultaneous movements of the nonparetic upper limb
      facilitate performance and recovery of paretic upper-limb function through neural
      coupling effects. OBJECTIVE: To determine whether the degree of coupling between
      both hands is higher after bilateral than after unilateral training and control
      treatment. METHODS: In a single-blinded randomized controlled trial, we
      investigated rhythmic interlimb coordination after unilateral (mCIMT) and
      bilateral (mBATRAC) upper-limb training and a dose-matched control treatment
      (DMCT) in 60 patients suffering from stroke. To this end, we used a series of
      tasks to discern intended and unintended coupling effects between the hands. In
      addition, we investigated the control over the paretic hand as reflected by
      movement harmonicity and amplitude. All tasks were performed before and after a 6
      week intervention period and at follow-up 6 weeks later. RESULTS: There were no
      significant between-group differences in change scores from baseline to
      postintervention and from postintervention to follow-up with regard to interlimb
      coupling. However, the mBATRAC group showed greater movement harmonicity and
      larger amplitudes with the paretic hand after training than the mCIMT and DMCT
      groups. CONCLUSIONS: The degree of coupling between both hands was not
      significantly higher after bilateral than after unilateral training and control
      treatment. Although improvements in movement harmonicity and amplitude following
      mBATRAC may indicate a beneficial influence of the interlimb coupling, those
      effects were more likely due to the particular type of limb movements employed
      during this training protocol.

PMID- 25055839
TI  - Sensor-based technology in the study of motor skills in infants at risk for ASD.
AB  - Motor impairments seems to play an important role in neurodevelopmental disorders
      such as autism spectrum disorders (ASD). Early detection of motor abnormalities
      during first years of life, may give important information regarding whether a
      child may receive a later diagnosis of Autism: for this reason an objective
      assessment of motor performance is crucial. While there are several technological
      solutions suitable to this end, they often require highly structured
      environments. In this work we propose the use of a magneto-inertial platform to
      study early motor performance between 12-36 months of age suitable to be used in
      non-structured environment.

PMID- 25055840
TI  - The role of N-acetylcysteine in the management of acute and chronic pulmonary
      complications of sulfur mustard: a literature review.
AB  - CONTEXT: Sulfur mustard exposure, as the most widely used chemical weapon, can
      lead to acute and long-term pulmonary complications via various pathways, such as
      triggering an imbalance between the oxidant and antioxidant system. Currently,
      there is no validated antidote, chemoprophylaxis and curative modality for
      pulmonary toxicities secondary to sulfur mustard exposure. OBJECTIVE: The aim of
      this literature review is to collect available experimental and clinical data on
      the efficacy of N-acetylcysteine (NAC), as a prominent antioxidant agent, in the
      prevention and/or treatment of sulfur mustard-induced acute and chronic pulmonary
      toxicities. METHODS: A literature search was performed by the relevant keywords
      like "N-acetyl cysteine", "Sulfur mustard" and "Lung injury" in databases such as
      Scopus, Medline, Embase and ISI Web of Knowledge. No time limitation was
      considered. Nineteen articles were selected for review. RESULTS: A number of in
      vitro and experimental studies concluded that oral, intravenous, intraperitoneal
      and intra-tracheal administration of NAC is effective in the management of sulfur
      mustard-induced acute lung injury, in a time-dependent manner, via direct
      scavenging, inhibition of oxidative stress, inflammatory responses and apoptosis.
      In addition, oral NAC alone (1200 or 1800 mg/day for 4 months) or at a dose 600
      mg/day for 6 months in combination with clarithromycin (500 mg/day) have led to
      improvements of clinical and paraclinical pulmonary parameters of patients with
      bronchiolitis obliterans due to sulfur mustard, through undetermined mechanisms.
      CONCLUSION: Despite limitations of relevant experimental and clinical studies,
      NAC can be considered as a candidate agent for prevention and/or treatment of
      sulfur mustard-induced acute lung injuries, as well as its long-term pulmonary
      toxicities, especially bronchiolitis obliterans.

PMID- 25055841
TI  - Respiratory tract lung geometry and dosimetry model for male Sprague-Dawley rats.
AB  - While inhalation toxicological studies of various compounds have been conducted
      using a number of different strains of rats, mechanistic dosimetry models have
      only had tracheobronchial (TB) structural data for Long-Evans rats, detailed
      morphometric data on the alveolar region of Sprague-Dawley rats and limited
      alveolar data on other strains. Based upon CT imaging data for two male Sprague
      Dawley rats, a 15-generation, symmetric typical path model was developed for the
      TB region. Literature data for the alveolar region of Sprague-Dawley rats were
      analyzed to develop an eight-generation model, and the two regions were joined to
      provide a complete lower respiratory tract model for Sprague-Dawley rats. The
      resulting lung model was used to examine particle deposition in Sprague-Dawley
      rats and to compare these results with predicted deposition in Long-Evans rats.
      Relationships of various physiologic variables and lung volumes were either
      developed in this study or extracted from the literature to provide the necessary
      input data for examining particle deposition. While the lengths, diameters and
      branching angles of the TB airways differed between the two Sprague-Dawley rats,
      the predicted deposition patterns in the three major respiratory tract regions
      were very similar. Between Sprague-Dawley and Long-Evans rats, significant
      differences in TB and alveolar predicted deposition fractions were observed over
      a wide range of particle sizes, with TB deposition fractions being up to 3- to 4
      fold greater in Sprague-Dawley rats and alveolar deposition being significantly
      greater in Long-Evans rats. Thus, strain-specific lung geometry models should be
      used for particle deposition calculations and interspecies dose comparisons.

PMID- 25055842
TI  - Design of an environmentally controlled rotating chamber for bioaerosol aging
      studies.
AB  - A chamber was designed and built to study the long-term effects of environmental
      conditions on air-borne microorganisms. The system consists of a 55.5-L
      cylindrical chamber, which can rotate at variable speeds on its axis. The chamber
      is placed within an insulated temperature controlled enclosure which can be
      either cooled or heated with piezoelectric units. A germicidal light located at
      the chamber center irradiates at a 360 degrees  angle. Access ports are located
      on the stationary sections on both ends of the chamber. Relative humidity (RH) is
      controlled by passing the aerosol through meshed tubes surrounded by desiccant.
      Validation assay indicates that the interior temperature is stable with less than
      0.5  degrees C in variation when set between 18 and 30  degrees C with the UV
      light having no effect of temperature during operation. RH levels set at 20%, 50%
      and 80% varied by 2.2%, 3.3% and 3.3%, respectively, over a 14-h period. The
      remaining fraction of particles after 18 h of suspension was 8.8% at 1 rotation
      per minute (rpm) and 2.6% at 0 rpm with the mass median aerodynamic diameter
      (MMAD) changing from 1.21 +/- 0.04 um to 1.30 +/- 0.02 um at 1 rpm and from 1.21
      +/- 0.04 um to 0.91 +/- 0.01 um at 0 rpm within the same time period. This
      chamber can be used to increase the time of particle suspension in an aerosol
      cloud and control the temperature, RH and UV exposure; the design facilitates
      stationary sampling to be performed while the chamber is rotating.

PMID- 25055843
TI  - Derivation of PM10 size-selected human equivalent concentrations of inhaled
      nickel based on cancer and non-cancer effects on the respiratory tract.
AB  - Abstract Nickel (Ni) in ambient air is predominantly present in the form of
      oxides and sulfates, with the distribution of Ni mass between the fine (particle
      aerodynamic diameter < 2.5 um; PM2.5) and coarser (2.5-10 um) size-selected
      aerosol fractions of PM10 dependent on the aerosol's origin. When deriving a long
      term health protective reference concentration for Ni in ambient air, the
      respiratory toxicity and carcinogenicity effects of the predominant Ni compounds
      in ambient air must be considered. Dosimetric adjustments to account for
      differences in aerosol particle size and respiratory tract deposition and/or
      clearance among rats, workers, and the general public were applied to
      experimentally- and epidemiologically-determined points of departure (PODs) such
      as no(low)-effect concentrations, for both cancer and non-cancer respiratory
      effects. This approach resulted in the derivation of threshold-based PM10 size
      selected equivalent concentrations (modified PODs) of 0.5 ug Ni/m(3) based on
      workers' cancer effects and 9-11 ug Ni/m(3) based on rodent respiratory toxicity
      effects. Sources of uncertainty in exposure extrapolations are described. These
      are not reference concentrations; rather the derived PM10 size-selected modified
      PODs can be used as the starting point for the calculation of ambient air
      reference concentrations for Ni. The described approach is equally applicable to
      other particulates. 

PMID- 25055844
TI  - Don't Come Late to the Party: Step Up and Lead.
AB  - Abstract  

PMID- 25055845
TI  - Safety climate and use of personal protective equipment and safety medical
      devices among home care and hospice nurses.
AB  - Use of personal protective equipment (PPE) and safety medical devices is mandated
      for healthcare workers to reduce the risk of infection with human
      immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus
      (HCV) from exposure to patients' blood. Research has shown that a strong safety
      climate may promote increased use of PPE. Therefore, the objective of this study
      was to examine the association between safety climate and use of PPE among
      homecare/hospice nurses in North Carolina. To this end, a mail survey was
      conducted in 2006. The response rate, adjusted on the assumption that the
      proportion of eligible nurses from among those who did not return the
      questionnaire or could not be contacted was similar to the proportion among those
      who did return the questionnaire, was 69% (n=833 eligibles). The percentage of
      nurses who used the specified PPE was two to three times greater among nurses who
      had a strong safety climate. Safety climate was only weakly associated with using
      safety devices. These results suggest that improving safety climate may be a
      powerful tool for increasing use of PPE. 

PMID- 25055846
TI  - Development of a high slip-resistant footwear outsole using a hybrid rubber
      surface pattern.
AB  - The present study examined whether a new footwear outsole with tread blocks and a
      hybrid rubber surface pattern, composed of rough and smooth surfaces, could
      increase slip resistance and reduce the risk of fall while walking on a wet floor
      surface. A drag test was performed to measure static and dynamic coefficient of
      friction (SCOF and DCOF, respectively) values for the footwear with the hybrid
      rubber surface pattern outsole and two types of commercially available boots that
      are conventionally used in food factories and restaurant kitchens with respect to
      a stainless steel floor covered with glycerol solution. Gait trials were
      conducted with 14 participants who wore the footwear on the wet stainless steel
      floor. The drag test results indicated that the hybrid rubber surface pattern
      sole exhibited higher SCOF (>=0.44) and DCOF (>=0.39) values than the soles of
      the comparative footwear (p<0.001). Because of such high SCOF and DCOF values,
      the slip frequency (p<0.01), slip distance (p<0.001), and slip velocity (p<0.001)
      for the footwear with the hybrid rubber surface pattern outsole were
      significantly lower than those for the comparative footwear, which resulted in no
      falls during trials. 

PMID- 25055847
TI  - Effects of computer-based stress management training on psychological well-being
      and work performance in japanese employees: a cluster randomized controlled
      trial.
AB  - This study evaluated the effectiveness of a computer-based stress management
      training (SMT) program in improving employees' psychological well-being and work
      performance. A total of 12 work units (N=263) were randomly assigned to either an
      intervention group (8 work units, n=142) or to a wait-list control group (4 work
      units, n=121). All participants were requested to answer online questionnaires
      assessing psychological well-being as a primary outcome, and coping style, social
      support, and knowledge about stress management as secondary outcomes at baseline
      (T0), immediately after the intervention (T1), and 2 months after the
      intervention (T2). The group * time interaction was tested using a mixed-model
      repeated measures ANOVA. Results showed a group * time interaction for "knowledge
      about stress management" in the entire sample. Among participants who had more
      than 3 d of training, a significant group * time interaction was observed for
      "problem-solving" and "avoidance and suppression" as well as "knowledge about
      stress management." Our computer-based stress management program was effective
      for improving knowledge about stress management. It was also effective for
      improving coping skills in instances where participants had enough time (at least
      3 d) to complete all sessions. 

PMID- 25055848
TI  - Socioeconomic and gender inequalities in job dissatisfaction among Japanese civil
      servants: the roles of work, family and personality characteristics.
AB  - This study examines (1) whether there are employment grade and gender differences
      in job dissatisfaction and (2) whether work, family, and personality
      characteristics explain grade and gender differences in job dissatisfaction. The
      participants were 3,812 civil servants, aged 20-65, working at a local government
      in Japan. In both males and females, low control, low social support, work-to
      family conflict, type A behaviour pattern and negative affectivity were
      significantly associated with job dissatisfaction. In females, high demands, long
      work hours and being unmarried were also associated with job dissatisfaction.
      Among males, in comparison with the highest grade employees, the age-adjusted
      odds ratio (OR) for job dissatisfaction in the lowest grade employees was 1.90
      (95% CI: 1.40-2.59). The grade differences reduced to 1.08 (0.76-1.54) after
      adjustment for work, family and personality characteristics. Among females,
      similar grade differences were observed, although the differences were not
      statistically significant. In comparison with males, the age-adjusted OR in
      females for job dissatisfaction was 1.32 (1.14-1.52). This gender difference was
      reduced to 0.95 (0.79-1.14) following adjustment for the other factors. The
      majority of employees belong to low to middle grades, and female employees have
      increased. Reducing grade and gender differences in work and family
      characteristics is needed. 

PMID- 25055849
TI  - The "ABCs of AD": A pilot test of an online educational module to increase use of
      the autonomic dysreflexia clinical practice guidelines among paramedic and nurse
      trainees.
AB  - CONTEXT/OBJECTIVE: Despite availability of clinical practice guidelines (CPGs),
      gaps in autonomic dysreflexia (AD) knowledge and practice persist. A free, online
      educational module, the "ABCs of AD", was developed to improve knowledge of the
      AD-CPGs among emergency healthcare personnel. We examine short-term changes in
      paramedic and nurse trainees' knowledge of, and social cognitions towards using,
      the AD-CPGs following module completion. DESIGN: Pre-post. METHODS: Thirty-four
      paramedic and nurse trainees from two training programs in Canada completed
      measures immediately before and after viewing the online "ABCs of AD" module.
      OUTCOME MEASURES: AD knowledge test; Theory of Planned Behavior social cognition
      questionnaire; module feedback survey. RESULTS: Paired samples t-tests revealed
      significant increases in participants' AD knowledge test scores (M +/- SDpre =
      9.00 +/- 2.46, M +/- SDpost = 12.03 +/- 4.07, P < 0.001; d = 0.84). Prior to
      viewing the module, participants reported positive social cognitions for using
      the AD-CPGs (all Ms >= 4.84 out of 7). From pre- to post-module, no significant
      changes were seen in participants' social cognitions for using the AD-CPGs.
      Participants' average module viewing time was 36.73 +/- 24.17 minutes (range 8-90
      minutes). There was a decline in viewing from the first to the last module
      sections, with only half of participants viewing all six sections. CONCLUSION:
      Knowledge alone is insufficient for clinical behavior change; as such, social
      cognitive determinants of behavior should be explicitly targeted in future
      iterations of the module to increase the likelihood of increased use of the AD
      CPGs. To engage viewers across all module sections, the "ABCs of AD" module
      should include supplementary learning strategies, such as interactive quizzes and
      peer-to-peer interaction.

PMID- 25055850
TI  - Oxidative skeletal rearrangement of 1,1'-binaphthalene-2,2'-diamines (BINAMs) via
      C-C bond cleavage and nitrogen migration: a versatile synthesis of U-shaped
      azaacenes.
AB  - An oxidative skeletal rearrangement of 1,1'-binaphthalene-2,2'-diamines (BINAMs)
      that involves the cleavage of a strong C-C single bond of the binaphthalene unit
      and the nitrogen migration has been discovered. The unprecedented rearrangement
      enables access to a series of U-shaped azaacenes otherwise difficult to prepare
      in a selective manner by classical methods. Moreover, physicochemical properties
      of the unique azaacenes have been comprehensively investigated. 

PMID- 25055851
TI  - Weight loss herbal intervention therapy (W-LHIT) a non-appetite suppressing
      natural product controls weight and lowers cholesterol and glucose levels in a
      murine model.
AB  - BACKGROUND: The prevalence of obesity is increasing in industrialized countries.
      Obesity increases the risk of coronary artery disease, stroke, cancer,
      hypertension, and type-2 diabetes. Unfortunately, conventional obesity drug
      treatment is often associated with adverse effects. The objective of this study
      was to evaluate a novel natural formula, Weight loss herbal intervention therapy
      (W-LHIT), developed from traditional Chinese medicine, for weight control in a
      high-fat-diet (HFD) induced obesity murine model. METHODS: Two sets of
      experiments were performed. In experiment 1, 14-week-old C57BL/6 J male mice were
      fed with HFD for 21 days and then separated into 3 weight-matched groups. One
      group continued on the HFD as obese-controls. Two groups were switched from HFD
      to normal fat level diet (NFD) and sham or W-LHIT treated. In experiment 2, 25
      week-old obese mice, following 2 weeks acclimatization, received either W-LHIT or
      sham treatment while maintained on HFD. In both sets of experiments, NFD fed, age
      matched normal weight mice served as normal controls. Body weight and food intake
      were recorded. Epididymal fat pad weight, serum glucose and cholesterol levels,
      as well as PPARgamma and FABP4 gene expression in epididymal fat tissue were
      analyzed at the end of the experiment. RESULTS: In experiment 1, W-LHIT treated
      obese mice lost body weight 12.2 +/- 3.8% whereas sham treated mice lost 5.5 +/-
      2.8% by day 10 after switching from the HFD to the NFD, without reduction of chow
      consumption. In experiment 2, W-LHIT treated obese mice maintained on the HFD had
      significantly lower body weight (8 fold less) than the sham treated mice. W-LHIT
      treatment also reduced epididymal fat pad weight, blood cholesterol and glucose
      levels versus sham treated mice without reduced chow consumption. In addition,
      significantly increased PPARgamma (peroxisome proliferator activated receptor
      gamma) and FABP4 (fatty acid binding protein 4) gene expression were found in
      epdidymal fat tissues. Liver and kidney function and hematology testing results
      of W-LHIT treated mice were within the normal range. CONCLUSIONS: W-LHIT
      significantly and safely reduced body weight, normalized glucose and cholesterol
      levels in obese mice, without suppression of appetite, and increased adipocyte
      PPARgamma and FABP4 gene expression.

PMID- 25055852
TI  - Primary and submovement control of aiming in C6 tetraplegics following posterior
      deltoid transfer.
AB  - BACKGROUND: Upper limb motor control in fast, goal-directed aiming is altered in
      tetraplegics following posterior-deltoid musculotendinous transfer. Specifically,
      movements have similar end-point accuracy but longer duration and lower peak
      velocity than those of age-matched, neurotypical controls. Here, we examine in
      detail the interplay between primary movement and submovement phases in five C6
      tetraplegic and five control participants. METHODS: Aiming movements were
      performed in two directions (20 cm away or toward), with or without vision.
      Trials that contained a submovement phase (i.e., discontinuity in velocity,
      acceleration or jerk) were identified. Discrete kinematic variables were then
      extracted on the primary and submovements phases. RESULTS: The presence of
      submovements did not differ between the tetraplegic (68%) and control (57%)
      groups, and almost all submovements resulted from acceleration and jerk
      discontinuities. Tetraplegics tended to make a smaller amplitude primary
      movement, which had lower peak velocity and greater spatial variability at peak
      velocity. This was followed by a larger amplitude and longer duration secondary
      submovement. Peak velocity of primary movement was not related to submovement
      incidence. Together, the primary and submovement phases of both groups were
      equally effective in reducing end-point error. CONCLUSIONS: C6 tetraplegic
      participants exhibit some subtle differences in measures of motor behaviour
      compared to control participants, but importantly feedforward and feedback
      processes work effectively in combination to achieve accurate goal-directed
      aiming.

PMID- 25055854
TI  - Retraction: Measuring Si-C60 chemical forces via single molecule spectroscopy.

PMID- 25055855
TI  - Time-specific microRNA changes during spinal motoneuron degeneration in adult
      rats following unilateral brachial plexus root avulsion: ipsilateral vs.
      contralateral changes.
AB  - BACKGROUND: Spinal root avulsion induces multiple pathophysiological events
      consisting of altered levels of specific genes and proteins related to
      inflammation, apoptosis, and oxidative stress, which collectively result in the
      death of the affected motoneurons. Recent studies have demonstrated that the gene
      changes involved in spinal cord injury can be regulated by microRNAs, which are a
      class of short non-coding RNA molecules that repress target mRNAs post
      transcriptionally. With consideration for the time course of the avulsion-induced
      gene expression patterns within dying motoneurons, we employed microarray
      analysis to determine whether and how microRNAs are involved in the changes of
      gene expression induced by pathophysiological events in spinal cord motoneurons.
      RESULTS: The expression of a total of 3,361 miRNAs in the spinal cord of adult
      rats was identified. Unilateral root-avulsion resulted in significant alterations
      in miRNA expression. In the ipsilateral half compared to the contralateral half
      of the spinal cord, on the 3rd day after the injury, 55 miRNAs were upregulated,
      and 24 were downregulated, and on the 14th day after the injury, 36 miRNAs were
      upregulated, and 23 were downregulated. The upregulation of miR-146b-5p and miR
      31a-3p and the downregulation of miR-324-3p and miR-484 were observed. Eleven of
      the miRNAs, including miR-21-5p, demonstrated a sustained increase; however, only
      miR-466c-3p presented a sustained decrease 3 and 14 days after the injury. More
      interestingly, 4 of the miRNAs, including miR-18a, were upregulated on the 3rd
      day but were downregulated on the 14th day after injury.Some of these miRNAs
      target inflammatory-response genes in the early stage of injury, and others
      target neurotransmitter transport genes in the intermediate stages of injury. The
      altered miRNA expression pattern suggests that the MAPK and calcium signaling
      pathways are consistently involved in the injury response. CONCLUSIONS: This
      analysis may facilitate the understanding of the time-specific altered expression
      of a large set of microRNAs in the spinal cord after brachial root avulsion.

PMID- 25055857
TI  - Editorial: The current state of the nation in evaluating the neonatal brain: Who?
      Why? How?

PMID- 25055858
TI  - Conventional (continuous) EEG monitoring in the NICU.
AB  - Conventional EEG is being used more frequently in NICUs in the U.S. with the
      advent of therapeutic hypothermia and the growth of neurocritical care
      intensivists & units. Historical applications have included assessing
      encephalopathy, seizure evaluation and prognosis. Past reluctance or limitation
      of the use in the NICU are receding with the digitization of EEG recordings and
      increasing interest in the neonatal brain. Continuous EEG monitoring is expanding
      the potential for its application as a brain monitoring tool to stratify initial
      injury severity, monitor seizure response to treatment, and detect sentinel
      neurologic events in the NICU, in addition to guiding neurotherapeutic options.
      The progression of the EEG background after an acute insult can also increase its
      prognostic specificity and provide another immediate marker of NICU neurologic
      outcome. The future of EEG monitoring in the NICU holds many possibilities and
      may greatly advance the new field of neuroprotection in the NICU. 

PMID- 25055859
TI  - Amplitude-integrated EEG and the newborn infant.
AB  - There is emerging recognition of the need for continuous long term electrographic
      monitoring of the encephalopathic neonate. While full-montage EEG with video
      remains the gold standard for monitoring, it is limited in application due to the
      complexity of lead application and specialized interpretation of results.
      Amplitude integrated EEG (aEEG) is derived from limited channels (usually C3-P3,
      C4-P4) and is filtered, rectified and time-compressed to serve as a bedside
      electrographic trend monitor. Its simple application and interpretation has
      resulted in increasing use in neonatal units across the world. Validation studies
      with full montage EEG have shown reliable results in interpretation of EEG
      background and electrographic seizures, especially when used with the
      simultaneously displayed raw EEG trace. Several aEEG monitors are commercially
      available and seizure algorithms are being developed for use on these monitors.
      These aEEG monitors, complement conventional EEG and offer a significant advance
      in the feasibility of long term electrographic monitoring of the encephalopathic
      neonate. 

PMID- 25055860
TI  - Cranial ultrasound - optimizing utility in the NICU.
AB  - Cranial ultrasonography (cUS) is a reliable tool to detect the most frequently
      occurring congenital and acquired brain abnormalities in full-term and preterm
      neonates. Appropriate equipment, including a dedicated ultrasound machine and
      appropriately sized transducers with special settings for cUS of the newborn
      brain, and ample experience of the ultrasonographist are required to obtain
      optimal image quality. When, in addition, supplemental acoustic windows are used
      whenever indicated and cUS imaging is performed from admission throughout the
      neonatal period, the majority of the lesions will be diagnosed with information
      on timing and evolution of brain injury and on ongoing brain maturation. For
      exact determination of site and extent of lesions, for detection of lesions that
      (largely or partially) remain beyond the scope of cUS and for depiction of
      myelination, a single, well timed MRI examination is invaluable in many high risk
      neonates. However, as cUS enables bedside, serial imaging it should be used as
      the primary brain imaging modality in high risk neonates. 

PMID- 25055856
TI  - Coat as a dagger: the use of capsid proteins to perforate membranes during non
      enveloped DNA viruses trafficking.
AB  - To get access to the replication site, small non-enveloped DNA viruses have to
      cross the cell membrane using a limited number of capsid proteins, which also
      protect the viral genome in the extracellular environment. Most of DNA viruses
      have to reach the nucleus to replicate. The capsid proteins involved in
      transmembrane penetration are exposed or released during endosomal trafficking of
      the virus. Subsequently, the conserved domains of capsid proteins interact with
      cellular membranes and ensure their efficient permeabilization. This review
      summarizes our current knowledge concerning the role of capsid proteins of small
      non-enveloped DNA viruses in intracellular membrane perturbation in the early
      stages of infection. 

PMID- 25055861
TI  - Magnetic resonance imaging in the encephalopathic term newborn.
AB  - Neonatal encephalopathy is a neurological emergency with heterogeneous etiologies
      and several management challenges. Neonatal encephalopathy of hypoxic-ischemic
      origin is associated with high rate of neonatal morbidity and mortality, and the
      long-term neurodevelopmental outcome of survivors with moderate to severe
      encephalopathy is poor. Magnetic resonance imaging now provides new insights on
      the diagnosis and prognosis of this condition. Typical patterns of brain injury
      have been recognized and in contemporary cohorts of newborns these patterns
      reflect different risk factors and clinical presentation, as well as specific
      patterns of neurodevelopmental outcome. Magnetic resonance spectroscopy,
      diffusion-weighted imaging, and diffusion tensor imaging are advanced MR
      techniques that are increasingly used in the assessment of encephalopathic
      newborns, providing innovative perspectives on neonatal brain metabolism,
      microstructure, and connectivity. These techniques have been particularly helpful
      in elucidating the unique time course of neonatal brain injury and in providing
      quantitative biomarkers for prognostication. To better refine the prognostic
      value of these new imaging tools, standardization of protocols, imaging
      modalities and scan timing are needed across centers. It is hoped that these
      techniques will permit earlier identification of newborns at risk of
      neurodevelopmental impairment and complement ongoing trials of emerging therapies
      such as hypothermia and novel pharmacological agents with neuroprotective
      properties. 

PMID- 25055862
TI  - Magnetic resonance spectroscopy biomarkers in term perinatal asphyxial
      encephalopathy: from neuropathological correlates to future clinical
      applications.
AB  - Neonatal brain injury remains a devastating condition, with poor outcomes despite
      the institution of an effective neuroprotective strategy of therapeutic
      hypothermia. There is an urgent need to develop additional neuroprotective
      strategies and to tailor our clinical predictive ability for families and their
      infants. Such goals could be more readily achieved if reliable early clinical
      indicators or biomarkers existed. This review will explore the relation between
      magnetic resonance (MR) imaging biomarkers and the degree of brain pathology
      observed in our translational piglet model of perinatal asphyxia. We also suggest
      biomarker relevance at a cellular level. The review will describe the development
      needed to optimize and simplify the use of biomarkers to speed up future trials
      of neuroprotection. 

PMID- 25055863
TI  - Magnetic resonance imaging of the preterm infant brain.
AB  - Despite improvements in neonatal care, survivors of preterm birth are still at a
      significantly increased risk of developing life-long neurological difficulties
      including cerebral palsy and cognitive difficulties. Cranial ultrasound is
      routinely used in neonatal practice, but has a low sensitivity for identifying
      later neurodevelopmental difficulties. Magnetic Resonance Imaging (MRI) can be
      used to identify intracranial abnormalities with greater diagnostic accuracy in
      preterm infants, and theoretically might improve the planning and targeting of
      long-term neurodevelopmental care; reducing parental stress and unplanned
      healthcare utilisation; and ultimately may improve healthcare cost effectiveness.
      Furthermore, MR imaging offers the advantage of allowing the quantitative
      assessment of the integrity, growth and function of intracranial structures,
      thereby providing the means to develop sensitive biomarkers which may be
      predictive of later neurological impairment. However further work is needed to
      define the accuracy and value of diagnosis by MR and the techniques's precise
      role in care pathways for preterm infants. 

PMID- 25055864
TI  - Advanced magnetic resonance imaging techniques in the preterm brain: methods and
      applications.
AB  - Brain development and brain injury in preterm infants are areas of active
      research. Magnetic resonance imaging (MRI), a non-invasive tool applicable to
      both animal models and human infants, provides a wealth of information on this
      process by bridging the gap between histology (available from animal studies) and
      developmental outcome (available from clinical studies). Moreover, MRI also
      offers information regarding diagnosis and prognosis in the clinical setting.
      Recent advances in MR methods - diffusion tensor imaging, volumetric
      segmentation, surface based analysis, functional MRI, and quantitative metrics -
      further increase the sophistication of information available regarding both brain
      structure and function. In this review, we discuss the basics of these newer
      methods as well as their application to the study of premature infants. 

PMID- 25055865
TI  - Neurobehavioral evaluation in the preterm and term infant.
AB  - Neurobehavioral examinations of babies, both term and preterm, have been used in
      neonatology for many decades. However, with the advent of new technologies and,
      perhaps more "scientific" ways of assessing high risk infants, it seems that
      neurobehavioral examinations may have become somewhat redundant in some
      nurseries. Yet these examinations remain an important part of clinical practice.
      They help to increase our understanding of an infant's behavior, including their
      strengths and vulnerabilities, thus enabling us to adjust our care and parent
      education accordingly. These examinations also assist us to identify those most
      at risk of developmental disabilities, enabling further assessment and
      intervention to be considered as early as possible. Whilst it remains a challenge
      to try and quantify neonatal neurobehavior, there are numerous tools available
      that can greatly assist us. This review did not find a tool that served all
      populations and all assessment purposes. Consequently, the clinician or
      researcher needs to choose the appropriate assessment depending on matters such
      as the infant's gestation and the assessment's goal and training requirements.
      Further research is needed to develop neurobehavioral assessment tools,
      particularly for extremely preterm infants, which are easily accessible in the
      clinical setting and can be used from birth. 

PMID- 25055866
TI  - Near infrared optical technologies to illuminate the status of the neonatal
      brain.
AB  - The neurodevelopmental outcome of at-risk infants in the neonatal intensive care
      unit (NICU) is concerning despite steady improvement in the survival rate of
      these infants. Our current management is often complicated by delayed realization
      of cerebral deficits due to late manifestation and lack of effective screening
      tools and neuroimaging/monitoring techniques that are suitable for sick neonates
      at the bedside. Near infrared specstrocopy (NIRS) is a noninvasive, safe, and
      portable technique providing a wide range of cerebral hemodynamic contrasts for
      evaluating the brain. The current state of NIRS technology can be devided into
      three generations. The first generation represents conventional trend monitoring
      oximeters that are currently the most widely used in the clinical settings, while
      the second generation focuses on improving the quantitive accuracy of NIRS
      measurements by advanced optical techniques. The emergence of diffuse optical
      imaging (DOI) represents a third generation which opens up more potential
      clinical applications by providing regional comparisons of brain oximetry and
      functions either at rest or in response to interventions. Successful integration
      of NIRS/DOI into the clinical setting requires matching the different
      capabilities of each instrument to specific clinical goals. 

PMID- 25055868
TI  - Genome-wide association study of electrocardiographic parameters identifies a new
      association for PR interval and confirms previously reported associations.
AB  - Previous reports have described several associations of PR, QRS, QT and heart
      rate with genomic variations by genome-wide association studies (GWASs). In the
      present study, we examined the association of ~2.5 million SNPs from 2994
      Japanese healthy volunteers obtained from the JPDSC database with
      electrocardiographic parameters. We confirmed associations of PR interval, QRS
      duration and QT interval in individuals of Japanese ancestry with 11 of the 45
      SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among
      individuals of European, African and Asian (Indian and Korean) ancestries. Those
      results indicate that many of the electrocardiographic associations with genes
      are shared by different ethnic groups including Japanese. Possible novel
      associations found in this study were validated by Korean data. As a result, we
      identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium
      calcium exchanger) (P = 7.595 * 10(-6)) with PR interval in Japanese individuals,
      and replication testing among Koreans confirmed the association of the same SNP
      with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets
      demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms
      (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 *
      10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory
      role of sodium-calcium exchanger in automaticity and conduction in sinoatrial
      node, atrium and atrioventricular node. Our findings support a functional role of
      sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as
      suggested by genetically modified mouse models. 

PMID- 25055867
TI  - SMN regulates axonal local translation via miR-183/mTOR pathway.
AB  - Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a
      neurodegenerative disorder leading to motor neuron dysfunction and loss. However,
      the molecular mechanisms by which SMN regulates neuronal dysfunction are not
      fully understood. Here, we report that reduced SMN protein level alters miRNA
      expression and distribution in neurons. In particular, miR-183 levels are
      increased in neurites of SMN-deficient neurons. We demonstrate that miR-183
      regulates translation of mTor via direct binding to its 3' UTR. Interestingly,
      local axonal translation of mTor is reduced in SMN-deficient neurons, and this
      can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression
      in the spinal cord of an SMA mouse model prolongs survival and improves motor
      function of Smn-mutant mice. Together, these observations suggest that axonal
      miRNAs and the mTOR pathway are previously unidentified molecular mechanisms
      contributing to SMA pathology. 

PMID- 25055869
TI  - Polycomb group complexes are recruited to reactivated FMR1 alleles in Fragile X
      syndrome in response to FMR1 transcription.
AB  - The FMR1 gene is subject to repeat mediated-gene silencing when the CGG-repeat
      tract in the 5' UTR exceeds 200 repeat units. This results in Fragile X syndrome,
      the most common heritable cause of intellectual disability and a major cause of
      autism spectrum disorders. The mechanism of gene silencing is not fully
      understood, and efforts to reverse this gene silencing have had limited success.
      Here, we show that the level of trimethylation of histone H3 on lysine 27, a
      hallmark of the activity of EZH2, a component of repressive Polycomb Group (PcG)
      complexes like PRC2, is increased on reactivation of the silenced allele by
      either the DNA demethylating agent 5-azadeoxycytidine or the SIRT1 inhibitor
      splitomicin. The level of H3K27me3 increases and decreases in parallel with the
      FMR1 mRNA level. Furthermore, reducing the levels of the FMR1 mRNA reduces the
      accumulation of H3K27me3. This suggests a model for FMR1 gene silencing in which
      the FMR1 mRNA generated from the reactivated allele acts in cis to repress its
      own transcription via the recruitment of PcG complexes to the FMR1 locus. 

PMID- 25055870
TI  - De novo CNVs in bipolar affective disorder and schizophrenia.
AB  - An increased rate of de novo copy number variants (CNVs) has been found in
      schizophrenia (SZ), autism and developmental delay. An increased rate has also
      been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we
      aimed to replicate these findings and compare de novo CNVs between SZ and BD. We
      used Illumina microarrays to genotype 368 BD probands, 76 SZ probands and all
      their parents. Copy number variants were called by PennCNV and filtered for
      frequency (<1%) and size (>10 kb). Putative de novo CNVs were validated with the
      z-score algorithm, manual inspection of log R ratios (LRR) and qPCR probes. We
      found 15 de novo CNVs in BD (4.1% rate) and 6 in SZ (7.9% rate). Combining
      results with previous studies and using a cut-off of >100 kb, the rate of de novo
      CNVs in BD was intermediate between controls and SZ: 1.5% in controls, 2.2% in BD
      and 4.3% in SZ. Only the differences between SZ and BD and SZ and controls were
      significant. The median size of de novo CNVs in BD (448 kb) was also intermediate
      between SZ (613 kb) and controls (338 kb), but only the comparison between SZ and
      controls was significant. Only one de novo CNV in BD was in a confirmed SZ locus
      (16p11.2). Sporadic or early onset cases were not more likely to have de novo
      CNVs. We conclude that de novo CNVs play a smaller role in BD compared with SZ.
      Patients with a positive family history can also harbour de novo mutations. 

PMID- 25055871
TI  - ZBTB42 mutation defines a novel lethal congenital contracture syndrome (LCCS6).
AB  - Lethal congenital contracture syndrome (LCCS) is a lethal autosomal recessive
      form of arthrogryposis multiplex congenita (AMC). LCCS is genetically
      heterogeneous with mutations in five genes identified to date, all with a role in
      the innervation or contractile apparatus of skeletal muscles. In a consanguineous
      Saudi family with multiple stillbirths presenting with LCCS, we excluded linkage
      to all known LCCS loci and combined autozygome analysis and whole-exome
      sequencing to identify a novel homozygous variant in ZBTB42, which had been shown
      to be enriched in skeletal muscles, especially at the neuromuscular junction.
      Knockdown experiments of zbtb42 in zebrafish consistently resulted in grossly
      abnormal skeletal muscle development and myofibrillar disorganization at the
      microscopic level. This severe muscular phenotype is successfully rescued with
      overexpression of the human wild-type ZBTB42 gene, but not with the mutant form
      of ZBTB42 that models the human missense change. Our data assign a novel muscular
      developmental phenotype to ZBTB42 in vertebrates and establish a new LCCS6 type
      caused by ZBTB42 mutation. 

PMID- 25055872
TI  - The co-chaperone and reductase ERdj5 facilitates rod opsin biogenesis and quality
      control.
AB  - Mutations in rhodopsin, the light-sensitive protein of rod cells, are the most
      common cause of autosomal dominant retinitis pigmentosa (ADRP). Many rod opsin
      mutations, such as P23H, lead to misfolding of rod opsin with detrimental effects
      on photoreceptor function and viability. Misfolded P23H rod opsin and other
      mutations in the intradiscal domain are characterized by the formation of an
      incorrect disulphide bond between C185 and C187, as opposed to the correct and
      highly conserved C110-C187 disulphide bond. Therefore, we tested the hypothesis
      that incorrect disulphide bond formation might be a factor that affects the
      biogenesis of rod opsin by studying wild-type (WT) or P23H rod opsin in
      combination with amino acid substitutions that prevent the formation of incorrect
      disulphide bonds involving C185. These mutants had altered traffic dynamics,
      suggesting a requirement for regulation of disulphide bond formation/reduction
      during rod opsin biogenesis. Here, we show that the BiP co-chaperone and
      reductase protein ERdj5 (DNAJC10) regulates this process. ERdj5 overexpression
      promoted the degradation, improved the endoplasmic reticulum mobility and
      prevented the aggregation of P23H rod opsin. ERdj5 reduction by shRNA delayed rod
      opsin degradation and promoted aggregation. The reductase and co-chaperone
      activity of ERdj5 were both required for these effects on P23H rod opsin.
      Furthermore, mutations in these functional domains acted as dominant negatives
      that affected WT rod opsin biogenesis. Collectively, these data identify ERdj5 as
      a member of the proteostasis network that regulates rod opsin biogenesis and
      supports a role for disulphide bond formation/reduction in rod opsin biogenesis
      and disease. 

PMID- 25055873
TI  - Renaturing membrane proteins in the lipid cubic phase, a nanoporous membrane
      mimetic.
AB  - Membrane proteins play vital roles in the life of the cell and are important
      therapeutic targets. Producing them in large quantities, pure and fully
      functional is a major challenge. Many promising projects end when intractable
      aggregates or precipitates form. Here we show how such unfolded aggregates can be
      solubilized and the solution mixed with lipid to spontaneously self-assemble a
      bicontinuous cubic mesophase into the bilayer of which the protein, in a
      confined, chaperonin-like environment, reconstitutes with 100% efficiency. The
      test protein, diacylglycerol kinase, reconstituted in the bilayer of the
      mesophase, was then crystallized in situ by the in meso or lipid cubic phase
      method providing an X-ray structure to a resolution of 2.55 A. This highly
      efficient, inexpensive, simple and rapid approach should find application
      wherever properly folded, membrane reconstituted and functional proteins are
      required where the starting material is a denatured aggregate. 

PMID- 25055874
TI  - Y(IO3)3 as a novel photocatalyst: synthesis, characterization, and highly
      efficient photocatalytic activity.
AB  - Nonbonding layer-structured Y(IO3)3 was successfully prepared by a simple
      hydrothermal route and investigated as a novel photocatalyst for the first time.
      Its crystal structure was characterized by X-ray diffraction, high-resolution
      transmission electron microscopy, and scanning electron microscopy. The optical
      absorption edge and band gap of Y(IO3)3 have been determined by UV-vis diffuse
      reflectance spectra. Theoretical calculations of the electronic structure of
      Y(IO3)3 confirmed its direct optical transition property near the absorption edge
      region, and the orbital components of the conduction band and valence band (VB)
      were also analyzed. The photocatalytic performance of Y(IO3)3 was evaluated by
      photooxidative decomposition of rhodamine B under ultraviolet light irradiation.
      It demonstrated that Y(IO3)3 exhibits highly efficient photocatalytic activity,
      which is much better than those of commercial TiO2 (P25) and important UV
      photocatalysts BiOCl and BiIO4. The origin of the excellent photocatalytic
      performance of Y(IO3)3 was investigated by electron spin resonance and
      terephthalic acid photoluminescence techniques. The results revealed that the
      highly strong photooxidation ability that resulted from its very positive VB
      position should be responsible for the excellent photocatalytic performance. 

PMID- 25055875
TI  - MicroRNA-204, a direct negative regulator of ezrin gene expression, inhibits
      glioma cell migration and invasion.
AB  - Ezrin is overexpressed in a variety of neoplastic cells and involved in the later
      stages of tumor progression and metastasis. Ezrin expression can be regulated at
      both the transcriptional and post-transcriptional levels. We used a combination
      of bioinformatics and experimental techniques to demonstrate that the miR-204 is
      a direct negative regulator of ezrin. Overexpression of miR-204 mimics decreased
      the activity of a luciferase reporter containing the ezrin 3' UTR and led to
      repression of ezrin protein. In contrast, ectopic expression of miR-204 inhibitor
      elevated ezrin expression. We also show that miR-204 is down-regulated in a panel
      of glioma tissues and in high invasive glioma cell lines we examined. Moreover,
      miR-204 mimics significantly reduced glioma cell migration and invasion, while
      miR-204 inhibitor generated the opposite results. Finally, overexpression of miR
      204 and knockdown of ezrin reduced glioma cell invasion, and these effects could
      be rescued by re-expression of ezrin. These findings reveal that miR-204 could be
      partly due to its inhibitory effects on glioma cell migration and invasion
      through regulating ezrin expression.

PMID- 25055876
TI  - Prevalence of the Helicobacter pylori babA2 gene and correlation with the degree
      of gastritis in infected Slovenian children.
AB  - The aims of our study were to determine the prevalence of the babA2 gene within
      Helicobacter pylori strains circulating in the Slovenian pediatric population, to
      further clarify its significance in causing inflammation of gastric mucosa in
      children and to verify whether cagA, vacA, iceA and babA genes work independently
      or synergistically in causing gastritis. A total of 163 H. pylori isolates
      obtained from the same number of children were tested for the presence of cagA,
      vacA and iceA genes using previously established methods, while the babA2 gene
      was determined using novel polymerase chain reaction assay targeting a 139-bp
      fragment of the central region of babA2. The babA2 gene was detected in 47.9% of
      H. pylori samples. The presence of the babA2 gene was strongly associated with
      cagA, vacA s1 and vacA m1 genotype. The babA2 status correlated positively with
      bacterial density score, activity of inflammation and chronic inflammation of
      gastric mucosa. No significant correlation was found between the babA2 status and
      the presence of atrophy or intestinal metaplasia. In addition, the activity of
      gastric inflammation and density score were significantly associated with the
      coexpression of the cagA, vacA s1, vacA m1 and babA2 genes. The study, which
      included the largest number of pediatric H. pylori samples to date, confirmed
      that babA2 gene plays an important role in the pathogenesis of H. pylori
      gastritis in children. Furthermore, our results suggest that babA2, cagA and vacA
      s1 and m1 gene products may work synergistically in worsening the inflammation of
      gastric mucosa.

PMID- 25055877
TI  - Benign neoplasm of the heart increases the risk of first ischemic stroke: a
      population-based cohort study.
AB  - OBJECTIVE: The study aims to investigate the incidence of first ischemic stroke
      in patients with benign cardiac tumors who did or did not undergo operations.
      METHODS: We used the National Health Insurance Research Database of Taiwan to
      conduct the research. The exposure cohort comprised 587 adult patients with
      benign cardiac tumors. Each patient was randomly frequency matched by age, index
      month, and index year with 10 participants from the general population who
      exhibited no history of benign cardiac tumors before the index date (control
      group). Cox's proportion hazard regression analyses were conducted to determine
      the relation between benign cardiac tumors and the risk of ischemic stroke.
      RESULTS: Based on clinical diagnoses, the prevalence of benign cardiac tumors was
      0.004%. Patients with benign cardiac tumors exhibited an increased risk of first
      ischemic stroke [adjusted hazard ratio: 1.77; (95% confidence interval, 1.20
      2.63)], particularly at young ages (adjusted hazard ratio: 22.9, 95% confidence
      interval: 4.17-126.0). We observed no significant difference in the risk of
      ischemic stroke between men with and without benign cardiac tumors (adjusted
      hazard ratio: 1.29, 95% confidence interval: 0.63-2.63). Among patients with
      benign cardiac tumors, the adjusted hazard ratio of first ischemic stroke was
      0.48 (95% confidence interval: 0.23-1.04) in the operation group compared with
      the nonoperation group. CONCLUSION: Younger patients (<50 years) with benign
      cardiac tumors exhibit an increased risk of first ischemic stroke.

PMID- 25055878
TI  - Pulmonary tuberculosis increases the risk of pulmonary thromboembolism: a
      nationwide population-based cohort study.

PMID- 25055879
TI  - Evidence-based mapping of design heterogeneity prior to meta-analysis: a
      systematic review and evidence synthesis.
AB  - BACKGROUND: Assessment of design heterogeneity conducted prior to meta-analysis
      is infrequently reported; it is often presented post hoc to explain statistical
      heterogeneity. However, design heterogeneity determines the mix of included
      studies and how they are analyzed in a meta-analysis, which in turn can
      importantly influence the results. The goal of this work is to introduce ways to
      improve the assessment and reporting of design heterogeneity prior to statistical
      summarization of epidemiologic studies. METHODS: In this paper, we use an
      assessment of sugar-sweetened beverages (SSB) and type 2 diabetes (T2D) as an
      example to show how a technique called 'evidence mapping' can be used to organize
      studies and evaluate design heterogeneity prior to meta-analysis.. Employing a
      systematic and reproducible approach, we evaluated the following elements across
      11 selected cohort studies: variation in definitions of SSB, T2D, and co
      variables, design features and population characteristics associated with
      specific definitions of SSB, and diversity in modeling strategies. RESULTS:
      Evidence mapping strategies effectively organized complex data and clearly
      depicted design heterogeneity. For example, across 11 studies of SSB and T2D, 7
      measured diet only once (with 7 to 16 years of disease follow-up), 5 included
      primarily low SSB consumers, and 3 defined the study variable (SSB) as
      consumption of either sugar or artificially-sweetened beverages. This exercise
      also identified diversity in analysis strategies, such as adjustment for 11 to 17
      co-variables and a large degree of fluctuation in SSB-T2D risk estimates
      depending on variables selected for multivariable models (2 to 95% change in the
      risk estimate from the age-adjusted model). CONCLUSIONS: Meta-analysis seeks to
      understand heterogeneity in addition to computing a summary risk estimate. This
      strategy effectively documents design heterogeneity, thus improving the practice
      of meta-analysis by aiding in: 1) protocol and analysis planning, 2) transparent
      reporting of differences in study designs, and 3) interpretation of pooled
      estimates. We recommend expanding the practice of meta-analysis reporting to
      include a table that summarizes design heterogeneity. This would provide readers
      with more evidence to interpret the summary risk estimates.

PMID- 25055880
TI  - Unilateral bicep curl hemodynamics: Low-pressure continuous vs high-pressure
      intermittent blood flow restriction.
AB  - Light-load exercise training with blood flow restriction (BFR) increases muscle
      strength and size. However, the hemodynamics of BFR exercise appear elevated
      compared with non-BFR exercise. This questions the suitability of BFR in
      special/clinical populations. Nevertheless, hemodynamics of standard prescription
      protocols for BFR and traditional heavy-load exercise have not been compared. We
      investigated the hemodynamics of two common BFR exercise methods and two
      traditional resistance exercises. Twelve young males completed four unilateral
      elbow flexion exercise trials in a balanced, randomized crossover design: (a)
      heavy load [HL; 80% one-repetition maximum (1-RM)]; (b) light load (LL; 20% 1
      RM); and two other light-load trials with BFR applied (c) continuously at 80%
      resting systolic blood pressure (BFR-C) or (d) intermittently at 130% resting
      systolic blood pressure (BFR-I). Hemodynamics were measured at baseline, during
      exercise, and for 60-min post-exercise. Exercising heart rate, blood pressure,
      cardiac output, and rate-pressure product were significantly greater for HL and
      BFR-I compared with LL. The magnitude of hemodynamic stress for BFR-C was between
      that of HL and LL. These data show reduced hemodynamics for continuous low
      pressure BFR exercise compared with intermittent high-pressure BFR in young
      healthy populations. BFR remains a potentially viable method to improve muscle
      mass and strength in special/clinical populations. 

PMID- 25055883
TI  - De novo sequencing, assembly, and analysis of the Taxodium 'Zhongshansa' roots
      and shoots transcriptome in response to short-term waterlogging.
AB  - BACKGROUND: Taxodium is renowned for its strong tolerance to waterlogging stress,
      thus it has great ecological and economic potential. However, the scant genomic
      resources in genus Taxodium have greatly hindered further exploration of its
      underlying flood-tolerance mechanism. Taxodium 'Zhongshansa' is an interspecies
      hybrid of T. distichum and T. mucronatum, and has been widely planted in
      southeastern China. To understand the genetic basis of its flood tolerance, we
      analyzed the transcriptomes of Taxodium 'Zhongshansa' roots and shoots in
      response to short-term waterlogging. RESULTS: RNA-seq was used to analyze genome
      wide transcriptome changes of Taxodium 'Zhongshansa 406' clone root and shoot
      treated with 1 h of soil-waterlogging stress. After de novo assembly, 108,692
      unigenes were achieved, and 70,260 (64.64%) of them were annotated. There were
      2090 differentially expressed genes (DEGs) found in roots and 394 in shoots, with
      174 shared by both of them, indicating that the aerial parts were also affected.
      Under waterlogging stress, the primary reaction of hypoxic-treated root was to
      activate the antioxidative defense system to prevent cells experiencing reactive
      oxygen species (ROS) poisoning. As respiration was inhibited and ATP decreased,
      another quick coping mechanism was repressing the energy-consuming biosynthetic
      processes through the whole plant. The glycolysis and fermentation pathway was
      activated to maintain ATP production in the hypoxic root. Constantly, the demand
      for carbohydrates increased, and carbohydrate metabolism were accumulated in the
      root as well as the shoot, possibly indicating that systemic communications
      between waterlogged and non-waterlogged tissues facilated survival. Amino acid
      metabolism was also greatly influenced, with down-regulation of genes involvedin
      serine degradation and up-regulation of aspartic acid degradation. Additionally,
      a non-symbiotic hemoglobin class 1 gene was up-regulated, which may also help the
      ATP production. Moreover, the gene expression pattern of 5 unigenes involving in
      the glycolysis pathway revealed by qRT-PCR confirmed the RNA-Seq data.
      CONCLUSIONS: We conclude that ROS detoxification and energy maintenance were the
      primary coping mechanisms of 'Zhongshansa' in surviving oxygen deficiency, which
      may be responsible for its remarkable waterlogging tolerance. Our study not only
      provided the first large-scale assessment of genomic resources of Taxodium but
      also guidelines for probing the molecular mechanism underlying 'Zhongshansa'
      waterlogging tolerance.

PMID- 25055884
TI  - Role of nuclear Lamin A/C in cardiomyocyte functions.
AB  - Lamin A/C is a structural protein of the nuclear envelope (NE) and cardiac
      involvement in Lamin A/C mutations was one of the first phenotypes to be reported
      in humans, suggesting a crucial role of this protein in the cardiomyocytes
      function. Mutations in LMNA gene cause a class of pathologies generically named
      'Lamanopathies' mainly involving heart and skeletal muscles. Moreover, the well
      known disease called Hutchinson-Gilford Progeria Syndrome due to extensive
      mutations in LMNA gene, in addition to the systemic phenotype of premature aging,
      is characterised by the death of patients at around 13 typically for a heart
      attack or stroke, suggesting again the heart as the main site sensitive to Lamin
      A/C disfunction. Indeed, the identification of the roles of the Lamin A/C in
      cardiomyocytes function is a key area of exploration. One of the primary
      biological roles recently conferred to Lamin A/C is to affect contractile cells
      lineage determination and senescence. Then, in differentiated adult
      cardiomyocytes both the 'structural' and 'gene expression hypothesis' could
      explain the role of Lamin A in the function of cardiomyocytes. In fact, recent
      advances in the field propose that the structural weakness/stiffness of the NE,
      regulated by Lamin A/C amount in NE, can 'consequently' alter gene expression.

PMID- 25055881
TI  - The cell envelope proteome of Aggregatibacter actinomycetemcomitans.
AB  - The cell envelope of gram-negative bacteria serves a critical role in maintenance
      of cellular homeostasis, resistance to external stress, and host-pathogen
      interactions. Envelope protein composition is influenced by the physiological and
      environmental demands placed on the bacterium. In this study, we report a
      comprehensive compilation of cell envelope proteins from the periodontal and
      systemic pathogen Aggregatibacter actinomycetemcomitans VT1169, an afimbriated
      serotype b strain. The urea-extracted membrane proteins were identified by mass
      spectrometry-based shotgun proteomics. The membrane proteome, isolated from
      actively growing bacteria under normal laboratory conditions, included 648
      proteins representing 27% of the predicted open reading frames in the genome.
      Bioinformatic analyses were used to annotate and predict the cellular location
      and function of the proteins. Surface adhesins, porins, lipoproteins, numerous
      influx and efflux pumps, multiple sugar, amino acid and iron transporters, and
      components of the type I, II and V secretion systems were identified. Periplasmic
      space and cytoplasmic proteins with chaperone function were also identified. A
      total of 107 proteins with unknown function were associated with the cell
      envelope. Orthologs of a subset of these uncharacterized proteins are present in
      other bacterial genomes, whereas others are found exclusively in A.
      actinomycetemcomitans. This knowledge will contribute to elucidating the role of
      cell envelope proteins in bacterial growth and survival in the oral cavity.

PMID- 25055885
TI  - Barriers to evidence-based treatment for children with attention
      deficit/hyperactivity disorder.
AB  - A number of evidence-based treatments are available for attention
      deficit/hyperactivity disorder (ADHD), including pharmacological, psychosocial,
      or a combination of the two treatments. For a significant number of children
      diagnosed with ADHD, however, these treatments are not utilized or adhered to for
      the recommended time period. Given that adherence to treatment regimens is
      necessary for reducing the symptoms of ADHD, it is crucial to develop a
      comprehensive understanding of why adherence rates are so low. The current review
      examines the literature to date that has directly explored utilization and
      adherence issues related to the treatment of ADHD in order to identify the key
      barriers to treatment. This review focused on four main factors that could
      account for the poor rates of treatment utilization and adherence: personal
      characteristics (socio-demographic characteristics and diagnostic issues),
      structural barriers, barriers related to the perception of ADHD, and barriers
      related to perceptions of treatment for ADHD. This review included 63 papers and
      covered a variety of barriers to treatment that have been found in research to
      have an impact on treatment adherence. Based on this review, we conclude that
      there are complex and interactive relationships among a variety of factors that
      influence treatment utilization and adherence. Four main gaps in the literature
      were identified: (1) there is limited information about barriers to psychosocial
      interventions, compared to pharmacological interventions; (2) there is a limited
      variety of research methodology being utilized; (3) treatment barrier knowledge
      is mostly from parents' perspectives; and (4) treatment utilization and treatment
      adherence are often studied jointly. Information from this review can help
      practitioners to identify potential barriers to their clients being adherent to
      treatment recommendations. 

PMID- 25055886
TI  - Physical impairments and quality of life of colorectal cancer survivors: a case
      control study.
AB  - The aim of the study is to determine the physical performance, quality of life
      and fatigue in colorectal cancer survivors compared with healthy controls. Twenty
      three colorectal cancer survivors and 22 matched controls were recruited for this
      case-control study. Fitness level (muscle trunk flexor endurance test, 6-min walk
      test, chair sit and reach test and flamingo test) was assessed in both groups.
      Participants completed the European Organization of Research and Treatment of
      Cancer, the Quality of Life Questionnaire (QLQ-C30), the Piper Fatigue Scale
      (PFS) and the International Fitness Scale (IFIS). Significant differences between
      groups were found for all fitness parameters (P < 0.05). In addition, the anova
      revealed significant differences in all of the IFIS scores (P < 0.001), PFS (P <
      0.01) and functioning scores of the QLQ-C30 (P < 0.05) between colorectal cancer
      survivors and the control group. The Mann-Whitney U-test showed a significant
      increase in symptom scores such as fatigue, dyspnoea and diarrhoea in the cancer
      survivors (P < 0.05). This study shows the existence of perceived and objective
      deterioration of health-related fitness level, presence of moderate cancer
      fatigue and reduced perceived quality of life in colorectal cancer survivors
      compared with healthy controls. 

PMID- 25055887
TI  - Ploidy-dependent survival of progeny arising from crosses between natural
      allotriploid Cobitis females and diploid C. taenia males (Pisces, Cobitidae).
AB  - Crosses between 21 triploid hybrid Cobitis females and 19 C. taenia (2n = 48)
      males led to viable progeny; whereas no embryonic development was observed in
      crosses with tetraploid males (4n = 98). The ploidy status of 491 progenies
      randomly selected with flow cytometry (316) or chromosome analysis (175) revealed
      an average of 55.2 % triploids and 44.8 % tetraploids, but the ratio of 3n versus
      4n fish did change during development. In the first 2 days after hatching,
      approximately 65.1 % of tetraploid larvae were observed. Their number decreased
      significantly to 30.8 and 6.2 % on average during 2-5 and 10-15 months of life,
      respectively. The karyotype of tetraploid progeny (4n = 98) included 3n = 74
      chromosomes of the parental female and n = 24 of C. taenia male. The number of
      tetraploid progeny indicated indirectly that about 66 % of eggs from 3n females
      were fertilized with C. taenia. The rest of the eggs developed clonally via
      gynogenesis or hemiclonally via hybridogenesis into triploids of the same
      karyotype structure as parental females. We have documented for the first time
      that (at least under experimental conditions) tetraploids are commonly formed,
      but are less viable than triploids, and a ratio similar to what is found under
      natural conditions is finally attained. The current explanation concerning the
      ploidy and karyotype structure of the progeny confirms that the eggs of 3n
      Cobitis females are not only capable of maintaining all chromosomes but are also
      capable of incorporating the sperm genome, thus creating the potential to produce
      tetraploids. 

PMID- 25055888
TI  - Use of phytoestrogens and effects perceived by postmenopausal women: result of a
      questionnaire-based survey.
AB  - BACKGROUND: Use of food supplements-containing phytoestrogens among
      postmenopausal women is rapidly increasing. Although phytoestrogens are often
      perceived as safe, evidence for overall positive risk-benefit profile is still
      inconclusive. The chance to buy them by user's initiative does not facilitate
      surveys on their prevalence and pattern of use. The aim of this study was to
      describe the pattern of use and self-reported positive and negative perceptions
      of phytoestrogens in post-menopausa. METHODS: A questionnaire was administered to
      women who were buying food supplements containing phytoestrogens in 22 pharmacies
      located in the Bologna area (400,000 inhabitants). Questionnaire was structured
      into 3 sections: (a) socio-demographic information, (b) pattern of use, (c)
      positive and negative perceptions. RESULTS: Data on 190 peri- and post-menopausal
      women (aged 38-77) were collected. Women stated to use phytoestrogens to reduce
      hot flushes (79%), insomnia (15%), mood disturbances (14%) and prevent
      osteoporosis (15%). The majority (59%) took phytoestrogens routinely, whereas 28%
      in 3-month cycles. Among positive perceptions between short- and long-term users,
      a not negligible difference was reported for relief of hot-flushes (68% in short
      term vs. 81% in long-term users; p = 0.04). Negative perceptions were reported
      more frequently in the long-term group, and this difference was statistically
      significant for edema (6% in short-term vs. 17% in long-term users; p = 0.04),
      but not for other effects: e.g., swelling sensation (10% vs. 21%; p = 0.09),
      somnolence (7% vs. 10% p = 0.62), fatigue (4% vs.11% p = 0.15). CONCLUSIONS: In
      the Bologna area, the pattern of use of phytoestrogens for menopausal symptoms is
      heterogeneous, and women overall find these substances to be beneficial,
      especially for relief of hot-flushes. Other positive perceptions decreased with
      long-term use. Negative perceptions, especially estrogen-like effects, seem to be
      infrequent and increase with long-term therapy. Physicians should pay attention
      to effects perceived by post-menopausal women and routinely monitor the use of
      phytoestrogens, in order to recognize possible adverse effects and actual
      benefits.

PMID- 25055889
TI  - Surgical transgastric debridement of walled off pancreatic necrosis: an option
      for patients with necrotizing pancreatitis.
AB  - BACKGROUND: Transgastric debridement of walled off pancreatic necrosis (WOPN) is
      a surgical treatment option for patients requiring pancreatic debridement for
      necrotizing pancreatitis. The reported experience with surgical transgastric
      pancreatic debridement is limited, however, the lower incidence of postoperative
      pancreatic fistulae with this procedure compared to other options warrants
      further evaluation of this technique. METHOD: Retrospective chart review.
      RESULTS: Twenty-two patients underwent transgastric debridement with a
      cystogastrostomy for clinically symptomatic WOPN from January 1, 2005 to July 31,
      2013. Eight cases were performed laparoscopically and 14 were performed by an
      open approach. The mean patient age was 50.9 (50.9 +/- 14.5) and the median
      American Society of Anesthesiologist score was 3. The most common etiology for
      pancreatitis was gallstones and the median time from attack of pancreatitis to
      definitive surgical management was 60 days (range 22-300 days). Median operative
      time was 182 min (range 85-327 min) with 100 cc (range 20-500 cc) of blood loss.
      In seven patients the necrosis was infected and in 15 patients the necrosis was
      sterile as determined by the intraoperative culture of the necrotic material. The
      overall significant morbidity (Clavien type 3 or greater) was 13.6 % and the
      mortality was 0 %. The incidence of postoperative pancreatic fistula was 0 %. 20
      patients (90 %) were symptom free during a median follow-up of 12 months.
      CONCLUSION: In selected patients with clinically symptomatic WOPN, surgical
      transgastric pancreatic debridement appears to be a safe procedure with a low
      morbidity and mortality. The low incidence of postoperative pancreatic fistulae
      warrants further evaluation.

PMID- 25055890
TI  - Laparoscopic left hepatectomy with tumor thrombectomy in patients with
      hepatocellular carcinoma concomitant with advanced portal vein tumor thrombus.
AB  - BACKGROUND: Although laparoscopic hepato-biliary-pancreatic surgery has been
      widely adopted, use of laparoscopic resection for hepatocellular carcinoma (HCC)
      with advanced portal vein tumor thrombus (PVTT) is uncommon because of the
      complications involved. METHODS: From June 2010 through November 2013, 200
      laparoscopic hepatectomies were performed. We report the short-term outcome of
      laparoscopic hepatectomy for HCC with advanced PVTT in 3 patients. Video
      presentation is a demonstration of the operative procedures employed in Case 3.
      In this case, the left hepatic artery and left hepatic duct were divided before
      tumor thrombectomy, and the bifurcation of the portal vein was clearly visible.
      RESULTS: Three female patients with HCC concomitant with PVTT in the portal trunk
      or the opposite branch underwent laparoscopic left hepatectomy with tumor
      thrombectomy using a laparoscopy-assisted technique (1 patient) or pure
      laparoscopic technique (2 patients). The median operative time was 592 min
      (range, 555-891 min), and median estimated blood loss was 1182 ml (range, minimal
      amount-4800 ml). The median length of hospital stay was 19 days (range, 9-22
      days), and there was no postoperative mortality. In Case 1, recurrent tumors
      developed in the residual lobe after curative resection, and the patient died 10
      months after the surgery despite treatment with sorafenib and transcatheter
      arterial chemoembolization. In Case 2, the patient survived for 10 months after
      curative resection without tumor recurrence. In Case 3, the patient was treated
      with sorafenib 1 month after palliative resection; she survived for 4
      postoperative months, during which decreased tumor marker levels were observed.
      CONCLUSIONS: Laparoscopic hepatectomy for HCC with advanced PVTT is a safe and
      feasible procedure in selected patients, when performed by surgeons with
      expertise in hepatic surgery and minimally invasive techniques. Although these
      patients cannot be cured by surgery alone, early adjuvant therapy followed by
      laparoscopic surgery might contribute to a good outcome.

PMID- 25055891
TI  - Esophagogastric junction distensibility measurements during Heller myotomy and
      POEM for achalasia predict postoperative symptomatic outcomes.
AB  - BACKGROUND: The functional lumen imaging probe (FLIP) is a novel diagnostic tool
      that can be used to measure esophagogastric junction (EGJ) distensibility. In
      this study, we performed intraoperative FLIP measurements during laparoscopic
      Heller myotomy (LHM) and peroral esophageal myotomy (POEM) for treatment of
      achalasia and evaluated the relationship between EGJ distensibility and
      postoperative symptoms. METHODS: Distensibility index (DI) (defined as the
      minimum cross-sectional area at the EGJ divided by distensive pressure) was
      measured with FLIP at two time points during LHM and POEM: (1) at baseline after
      induction of anesthesia, and (2) after operation completion. RESULTS:
      Measurements were performed in 20 patients undergoing LHM and 36 undergoing POEM.
      Both operations resulted in an increase in DI, although this increase was larger
      with POEM (7 +/- 3.1 vs. 5.1 +/- 3.4 mm(2)/mmHg, p < .05). The two patients (both
      LHM) with the smallest increases in DI (1 and 1.6 mm(2)/mmHg) both had persistent
      symptoms postoperatively and, overall, LHM patients with larger increases in DI
      had lower postoperative Eckardt scores. In the POEM group, there was no
      correlation between change in DI and symptoms; however, all POEM patients
      experienced an increase in DI of >3 mm(2)/mmHg. When all patients were divided
      into thirds based on final DI, none in the lowest DI group (<6 mm(2)/mmHg) had
      symptoms suggestive of reflux (i.e., GerdQ score >7), as compared with 20 % in
      the middle third (6-9 mm(2)/mmHg) and 36 % in the highest third (>9 mm(2)/mmHg).
      Patients within an "ideal" final DI range (4.5-8.5 mm(2)/mmHg) had optimal
      symptomatic outcomes (i.e., Eckardt <= 1 and GerdQ <= 7) in 88 % of cases,
      compared with 47 % in those with a final DI above or below that range (p < .05).
      CONCLUSIONS: Intraoperative EGJ distensibility measurements with FLIP were
      predictive of postoperative symptomatic outcomes. These results provide initial
      evidence that FLIP has the potential to act as a useful calibration tool during
      operations for achalasia.

PMID- 25055892
TI  - Assessment and reduction of diaphragmatic tension during hiatal hernia repair.
AB  - BACKGROUND: During hiatal hernia repair there are two vectors of tension: axial
      and radial. An optimal repair minimizes the tension along these vectors. Radial
      tension is not easily recognized. There are no simple maneuvers like measuring
      length that facilitate assessment of radial tension. The aims of this project
      were to: (1) establish a simple intraoperative method to evaluate baseline
      tension of the diaphragmatic hiatal muscle closure; and, (2) assess if tension is
      reduced by relaxing maneuvers and if so, to what degree. METHODS: Diaphragmatic
      characteristics and tension were assessed during hiatal hernia repair with a
      tension gage. We compared tension measured after hiatal dissection and after
      relaxing maneuvers were performed. RESULTS: Sixty-four patients (29 M:35F)
      underwent laparoscopic hiatal hernia repair. Baseline hiatal width was 2.84 cm
      and tension 13.6 dag. There was a positive correlation between hiatal width and
      tension (r = 0.55) but the strength of association was low (r (2) = 0.31). Four
      different hiatal shapes (slit, teardrop, "D", and oval) were identified and
      appear to influence tension and the need for relaxing incision. Tension was
      reduced by 35.8 % after a left pleurotomy (12 patients); by 46.2 % after a right
      crural relaxing incision (15 patients); and by 56.1 % if both maneuvers were
      performed (6 patients). CONCLUSIONS: Tension on the diaphragmatic hiatus can be
      measured with a novel device. There was a limited correlation with width of the
      hiatal opening. Relaxing maneuvers such as a left pleurotomy or a right crural
      relaxing incision reduced tension. Longer term follow-up will determine whether
      outcomes are improved by quantifying and reducing radial tension.

PMID- 25055893
TI  - Few comments on "laparoscopic splenectomy: perioperative management, surgical
      technique, and results".

PMID- 25055894
TI  - The influence of tai chi and yoga on balance and falls in a residential care
      setting: a randomised controlled trial.
AB  - Abstract Falls amongst older people is a global public health concern. Whilst
      falling is not a typical feature of ageing, older people are more likely to fall.
      Fall injuries amongst older people are a leading cause of death and disability.
      Many older people do not do regular exercise so that they lose muscle tone,
      strength, and flexibility which affect balance and predispose them to falls. The
      management of falls in residential care settings is a major concern with
      strategies for prevention and monitoring a focus in this setting. Yoga and tai
      chi have shown potential to improve balance and prevent falls in older adults.
      They also have potential to improve pain and quality of life. The aim of this
      study was to determine the feasibility of conducting a 3-arm RCT with frail older
      people in a residential care setting to test the hypothesis that a 14 week
      modified tai chi or yoga program is more effective than usual care activity in
      improving balance function, quality of life, pain experience and in reducing
      number of falls. There were no statistically significant differences between the
      three groups in the occurrence of falls. Yoga demonstrated a slight decrease in
      fall incidence; quality of life improved for the tai chi group. Only the yoga
      group experienced a reduction in average pain scores though not statistically
      significant. The findings of the study suggest it is possible to safely implement
      modified yoga and tai chi in a residential care setting and evaluate this using
      RCT design. They show positive changes to balance, pain and quality of life and a
      high level of interest through attendance amongst the older participants. The
      results support offering tai chi and yoga to older people who are frail and
      dependent with physical and cognitive limitations.

PMID- 25055896
TI  - Full-length characterization of transcribed genomic regions.
AB  - In the last years, an enormous progress has been made in the identification of
      genomic sequences. Given that genomic sequences can have various functions (e.g.,
      structural organization, gene regulation, transcriptional start, and protein
      coding), molecular characterization is essential for progressing from the initial
      identification of genomic sequences to the delineation of a specific biological
      mechanism. Mapping of transcribed sequences is the initial step in functional
      characterization of genomic sequences. Northern blot analysis allows for a direct
      and detailed characterization of transcribed sequences, like size and splicing
      variants, and provides a relative comparison of transcript abundance between
      different cellular conditions. This method includes separation of total cellular
      RNA by size via gel electrophoresis, RNA transfer to a membrane, and RNA
      hybridization with a complementary labeled genomic probe. 

PMID- 25055895
TI  - Negative colposcopy reduces precancer risk after low-grade cytology.

PMID- 25055897
TI  - Rapid mapping of RNA 3' and 5' ends.
AB  - In recent years, an enormous progress has been made in applied genomics leading
      to identification and isolation of novel cDNAs. However, most attempts result in
      the acquisition of transcribed sequences that represent only a part of the mRNA's
      complete sequence. Rapid Amplification of cDNA Ends (RACE) is a technique used in
      molecular biology to obtain the full length sequence of an RNA transcript found
      within a cell. Since the first report of this technique, many significant
      improvements have been made on the basic approach. This chapter describes the
      most recent update of the relatively simple and versatile classic RACE protocol. 

PMID- 25055898
TI  - Single nucleotide mapping of RNA 5' and 3' ends.
AB  - Nuclease protection assay is a sensitive method for detection, quantitation, and
      mapping of a specific RNA in an extremely heterogeneous mixture of RNAs, such as
      total cellular RNA. The assay is based on a small volume solution hybridization
      of a single-stranded synthetic antisense and labeled RNA probe to a RNA sample.
      Thus, it is much more efficient than the common immobilized hybridization on a
      membrane, such as in northern-blot analysis. After solution hybridization,
      different nucleases are used to remove any remaining single-stranded nucleotides
      within the probe and sample RNA by digestion. Then, the remaining probe-target
      hybrids are purified and separated on a denaturing polyacrylamide gel. Using a
      radioactive labeled probe, the protected probe can be visualized by direct
      autoradiography and the copy number can be calculated based on the specific
      radioactivity of the RNA probe and the length of protected fragment. Because of
      its high sensitivity and resolution, nuclease protection assay is the most
      effective procedure for mapping internal and external boundaries in mRNA compared
      to other RNA detection methods such as RT-PCR. 

PMID- 25055899
TI  - Analysis of RNA secondary structure.
AB  - RNA has different levels of structural organization. The primary structure is the
      linear order of the nucleotide monomers, the RNA sequence. During transcription
      process, the partially synthesized RNA is folded by base-pairing and
      thermodynamic intramolecular or intermolecular interactions. This results in a
      dynamic spreading of a secondary structure along the length of the transcribed
      section of the RNA. The analysis of both primary or secondary structures requires
      the RNA end-labeling either at its 5' end using a kinase reaction with [gamma
      32P]ATP, or at its 3' end using an RNA ligation reaction with [32P]pCp. End
      labeled RNAs are then gradually breakdown using hydrolysing chemicals or a
      variety of enzymes targeting specific RNA sequences and secondary structure. The
      most commonly used enzymes are RNase A, T1, and V1. The partial digestion of the
      RNA reveals a mix of truncated RNA fragments of different lengths, called RNA
      ladder. The products are then separates through a high resolution gel system and
      subjected to autoradiographic analysis. Each visible fragment is labeled at one
      end, but comprises an enzyme specific sequence at the other end. Final comparison
      of the detected RNA ladders reveals a hypothetical model of the secondary RNA
      structure under assay conditions. 

PMID- 25055900
TI  - Tertiary structure mapping of the pri-miRNA miR-17~92.
AB  - The understanding of RNA in regulating gene expression has exploded over the past
      15 years. MicroRNAs (miRNAs) have vastly expanded the role of RNA in gene
      regulation beyond spliceosomal, ribosomal, and messenger RNAs. Approximately one
      half of miRNAs are polycistronic, where two or more miRNAs are encoded on a
      single pri-miRNA transcript, termed a miRNA cluster. The six miRNAs of the miR
      17~92 cluster are contained within a ~800 nucleotide region within intron 3 of
      the cl13orf25 ~7 kb pri-miRNA transcript. We recently reported on the tertiary
      structured domain of miR-17~92 and its role in modulating miRNA biogenesis. The
      key finding was that the cluster structure explained the differential processing
      of the miRNA hairpins by Drosha. This work demonstrated the need to consider pri
      miRNA tertiary structure in miRNA biogenesis. Since biochemical structure probing
      is typically performed on relatively short RNAs (<=200 nucleotides), we had to
      adapt these methodologies for application on large RNAs (~800 nucleotide miR
      17~92 pri-miRNA). We present here our adaptation of a protection footprinting
      method using ribonucleases to probe the structure of the ~800 nucleotide miR
      17~92 pri-miRNA. We outline the technical difficulties involved in probing large
      RNAs and data visualization using denaturing polyacrylamide gel electrophoresis
      and how we adapted the existing approaches to probe large RNAs. The methodology
      outlined here is generally applicable to large RNAs including long noncoding RNAs
      (lncRNA). 

PMID- 25055901
TI  - In situ hybridization detection of miRNA using LNATM oligonucleotides.
AB  - MicroRNAs are a family of small noncoding ribonucleic acids involved in
      regulation of gene activity. They have been implicated in both normal cellular
      pathways related to proliferation, differentiation, and apoptosis and
      pathological processes leading to disease. It is believed that better
      understanding of their structure and function will shed more light on a number of
      cellular functions while at the same time providing the basis for development of
      novel therapeutic applications. That is why identification and quantification of
      miRNAs are of great scientific interest. Several techniques have been developed
      which allow accurate, fast, and easy detection of these RNA species. This chapter
      focuses on in situ hybridization (ISH), a method which combines identification of
      miRNAs with histochemistry (ICH). We describe in detail a protocol for ISH in
      formalin-fixed paraffin-embedded tissue with the help of synthetic nonradioactive
      LNA oligonucleotide probes. 

PMID- 25055902
TI  - Quantification of miRNAs by a simple and specific qPCR method.
AB  - MicroRNAs (miRNAs) are powerful regulators of gene expression at
      posttranscriptional level and play important roles in many biological processes
      and in disease. The rapid pace of the emerging field of miRNAs has opened new
      avenues for development of techniques to quantitatively determine miRNA
      expression levels in different systems. In this chapter we describe a PCR method
      for quantification of miRNAs based on a single reverse transcription reaction for
      all miRNAs combined with real-time PCR with two miRNA-specific DNA primers. This
      method quantifies synthetic templates over eight orders of magnitude and
      successfully discriminates miRNAs that differ by one single nucleotide. Due to
      the usage of DNA primers this method allows higher amplification efficiencies
      than a similar method based on locked nucleic acid-spiked primers. The high
      efficiency translates into higher sensitivity and precision in miRNA
      quantification. Furthermore, the method is easy to perform with common laboratory
      reagents, which allows miRNA quantification at low cost.

PMID- 25055903
TI  - RNA isolation for small RNA Next-Generation Sequencing from acellular biofluids.
AB  - There are a number of considerations when choosing protocols both upstream and
      downstream of Next-Generation Sequencing experiments. On the front end,
      purification methods, additives, and residuum can often inhibit the sensitive
      chemistries by which sequencing-by-synthesis is performed. On the back end, data
      handling, analysis software packages, and pipelines can also impact sequencing
      outcomes. The current chapter will describe stepwise how acellular biofluid
      samples are prepared for small RNA sequencing. With regard to purification
      methods, we found that small RNA yield can be improved considerably by following
      the total RNA isolation protocol included with Ambion's mirVana PARIS Kit but
      modifying the organic extraction step. Specifically, after transferring the upper
      aqueous phase to a fresh tube, water is added to the residual material
      (interphase and lower organic layer) and again phase-separated. In contrast, all
      the protocols provided with the commercially available kits at the time of this
      chapter publication require only one organic extraction. This simple yet, as it
      turns out, quite useful modification allows access to previously inaccessible
      material. Potential benefits from these changes are a more comprehensive sample
      profiling of small RNA, as well as wider access to small volume samples, such as
      is typically available for acellular biofluids, which now can be prepared for
      small RNA sequencing on the Illumina platform.

PMID- 25055904
TI  - Sequencing small RNA: introduction and data analysis fundamentals.
AB  - Small RNAs are important transcriptional regulators within cells. With the advent
      of powerful Next Generation Sequencing platforms, sequencing small RNAs seems to
      be an obvious choice to understand their expression and its downstream effect.
      Additionally, sequencing provides an opportunity to identify novel and
      polymorphic miRNA. However, the biggest challenge is the appropriate data
      analysis pipeline, which is still in phase of active development by various
      academic groups. This chapter describes basic and advanced steps for small RNA
      sequencing analysis including quality control, small RNA alignment and
      quantification, differential expression analysis, novel small RNA identification,
      target prediction, and downstream analysis. We also provide a list of various
      resources for small RNA analysis. 

PMID- 25055905
TI  - Measuring expression levels of small regulatory RNA molecules from body fluids
      and formalin-fixed, paraffin-embedded samples.
AB  - MicroRNAs are involved in the regulation of various pathophysiological processes
      such as immune regulation and cancer. Next-generation sequencing methods enable
      us to monitor their presence in various types of samples but we need flexible
      methods for validating datasets generated by high-throughput methods. Here we
      describe the detailed protocols to be used with our MiRNA Primer Design Tool
      assay design system. The presented methods allow the flexible design of the
      oligonucleotides needed for the RT-qPCR detection of any variant of small
      regulatory RNA molecules from virtually any species. This method can be used to
      measure miRNA levels from formalin-fixed, paraffin-embedded (FFPE) samples and
      various body fluids. As an example, we show the results of the hsa-miR-515-3p,
      hsa-miR-325, and hsa-miR-155 quantification using a specific UPL probe (Universal
      Probe Library) and a stem-loop RT-qPCR assay. The small nucleolar RNA RNU43 is
      used as endogenous control for normalization of the results. Urine from healthy
      pregnant women and FFPE samples from patients diagnosed with colorectal cancer
      and treated with antibody-based anti-EGFR monotherapy were used as samples.

PMID- 25055906
TI  - MicroRNA profiling in plasma or serum using quantitative RT-PCR.
AB  - MicroRNAs (miRNAs) are important cellular modulators that regulate gene
      expression at the posttranscriptional level. Circulating miRNAs present in human
      plasma or serum have recently become an emerging field in biomedical research,
      mostly due to its potential applications in the diagnosis and prognosis of
      several diseases. Although miRNA profiling in biofluids holds great promise,
      there are several challenges to overcome. Here, we present an experimental
      procedure for profiling miRNA in plasma or serum with high sensitivity and
      specificity using qRT-PCR. This method is also suitable for studying miRNAs in
      other body fluids or clinical samples that also contain low amounts of RNA. 

PMID- 25055907
TI  - MicroRNA profiling of exosomes isolated from biofluids and conditioned media.
AB  - Exosomes are membrane-bound 50-100 nm vesicles released from many cell types
      including normal and tumorous tissues. Exosomes transport mainly miRNAs, mRNAs,
      enzymes, cytokines, etc. from the cells of origin to the neighbor cells mediating
      the communication between them. The content of exosomes can be explored using RNA
      profiling after their isolation from medium conditioned by cultured cells or from
      other biofluids. This chapter includes detailed discussion on isolation,
      characterization, and miRNA profiling of exosomes. First, exosomes are isolated
      by filtration and ultracentrifugation, and then characterized using
      immunoblotting and transmission electron microscope. Finally, we used low density
      arrays to profile exosomal miRNA.

PMID- 25055908
TI  - Isolation of urinary exosomes for RNA biomarker discovery using a simple, fast,
      and highly scalable method.
AB  - Urinary exosomes are nanovesicles (40-100 nm) of endocytic origin that are
      secreted into the urine when a multivesicular body fuses with the membrane of
      cells from all nephron segments. Interest in urinary exosomes intensified after
      the discovery that they contain not only protein and mRNA but also microRNA
      (miRNA) markers of renal dysfunction and structural injury. Currently, the most
      widely used protocol for the isolation of urinary exosomes is based on
      ultracentrifugation, a method that is time consuming, requires expensive
      equipment, and has low scalability, which limits its applicability in the
      clinical practice. In this chapter, a simple, fast, and highly scalable step-by
      step method for isolation of urinary exosomes is described. This method starts
      with a 10-min centrifugation of 10 ml urine, then the supernatant is saved (SN1),
      and the pellet is treated with dithiothreitol and heat to release and recover
      those exosomes entrapped by polymeric Tamm-Horsfall protein. The treated pellet
      is then resuspended and centrifuged, and the supernatant obtained (SN2) is
      combined with the first supernatant, SN1. Next, 3.3 ml of ExoQuick-TC, a
      commercial exosome precipitation reagent, is added to the total supernatant (SN1
      + SN2), mixed well, and saved for at least 12 h at 4  degrees C. Finally, a
      pellet of exosomes is obtained after a 30-min centrifugation of the
      supernatant/ExoQuick-TC mix. We previously compared this method with five others
      used to isolate urinary exosomes and found that this is the simplest, fastest,
      and most effective alternative to ultracentrifugation-based protocols if the goal
      of the study is RNA profiling. A method for isolation and quantification of
      miRNAs and mRNAs from urinary exosomes is also described here. In addition, we
      provide a step-by-step description of exosomal miRNA profiling using universal
      reverse transcription and SYBR qPCR.

PMID- 25055909
TI  - Identification of actively translated mRNAs.
AB  - Ribosomes are large protein-RNA complexes involved in translation of mRNA
      nucleotide sequences into proteins. Multiple ribosomes, polyribosomes
      (polysomes), bind to a single mRNA in order to initiate translation and protein
      synthesis. In order to distinguish actively translated RNAs, total polysomes can
      be isolated from cell lysates and purified by centrifugation through sucrose
      density gradients. The polysome fraction represents all actively translated
      cellular RNAs that can be specifically detected using common RNA detection
      assays, e.g., RT-PCR. The quantity of the target RNA in polysomes fraction
      indicates its translation state. This chapter provides a protocol for the
      isolation and fractionation of polysomes from mammalian cell lines. 

PMID- 25055910
TI  - Mapping of internal ribosome entry sites (IRES).
AB  - The dicistronic luciferase reporter gene system is the most common method to
      isolate and characterize internal ribosome entry sites (IRES). It is based on the
      expression of a dicistronic RNA comprising two independent reporter genes in 3'
      and 5'cistrons, and the putative IRES inserted into intercistronic region. The
      most convenient aspect of using Renilla and firefly luciferase genes is that both
      gene products can be detected in a single assay using Dual-Luciferase((r))
      Reporter Assay System from Promega. The Renilla luciferase coding sequence is
      often inserted into the 5'cistron and serves as internal control. It is
      translated cap dependently, as it is close to the cap structure at the 5' end.
      The 3'cistron located far downstream to the cap structure can only be translated
      by a cap-independent mechanism when the intercistronic sequence is capable of
      ribosome binding and re-initiation of translation. Expression level of the
      3'cistron is usually normalized to the expression of 5'cistron to estimate the
      relative IRES activity of intercistronic sequences. 

PMID- 25055911
TI  - Mapping of protein binding RNA elements.
AB  - The RNA electrophoretic mobility shift assay is a very versatile method to study
      a broad spectrum of RNA-protein interactions. The technique is based on the
      separation of protein RNA mixtures through a native acrylamide gel. Compared to
      unbound RNA, RNA-protein complexes migrate slower through the gel resulting in a
      mass shift. The RNA EMSA can be used to identify unknown RNA-protein complexes,
      to map the RNA binding site of single proteins or determine the specificity of
      RNA-protein complexes using specific antibodies resulting in retarded migration
      through the gel. 

PMID- 25055912
TI  - Purification of RNA-binding proteins.
AB  - The majority of regulatory RNA sequences exert their function through interaction
      with proteins. Therefore, the identification of RNA-binding proteins is the key
      step in understanding the role of many RNA motifs. Here, we describe a
      straightforward method to identify RNA-binding proteins. In this approach, RNAs
      are immobilized on beads and incubated with protein lysates. After removing
      unbound fraction of proteins, the bound proteins are eluted by successive
      increasing of salt concentration. The lower the salt concentration, the lower is
      the binding affinity of a protein to the RNA. According to this principle, each
      elution fraction can contain a number of proteins which bind with similar
      affinity to the RNA. After gel electrophoretic separation and staining, each
      single protein band can be identified, isolated, and analyzed by mass
      spectrometry. 

PMID- 25055913
TI  - De novo approach to classify protein-coding and noncoding transcripts based on
      sequence composition.
AB  - Each day, more and more transcripts are being discovered along the genome
      (especially in poorly annotated species) thanks to the rapid progress of high
      throughput technology such as RNA sequencing. However, this situation unravels
      the challenge of how to classify the newly identified transcripts into protein
      coding or noncoding. Here, we describe a de novo approach named coding-noncoding
      index (CNCI), a powerful signature tool by profiling adjoining nucleotide
      triplets (ANT) to effectively distinguish between protein-coding and noncoding
      sequences independently of known annotations. The main advantage of CNCI is its
      ability to accurately classify transcripts assembled from whole-transcriptome
      sequencing data in a cross-species manner, which allowed it to be used for all
      vertebrates and invertebrates based on the training data of well-annotated
      species (such as human and Arabidopsis). In this chapter, we illustrate the CNCI
      method in detail through an example of RNA-sequencing data generated from six
      biological replicates of six mouse tissues. CNCI software is available at
      http://www.bioinfo.org/software/cnci.

PMID- 25055914
TI  - Computational methods to predict long noncoding RNA functions based on co
      expression network.
AB  - Although long noncoding RNAs (lncRNAs) have been recognized in recent years to
      constitute a significant portion of mammalian transcriptome, and the functional
      impact of several lncRNAs has been characterized by a few studies, yet it is
      still difficult to large-scale ascertain their functions from lab experiment or
      structure prediction. To address this deficit, we have developed a computational
      pipeline to large-scale annotate the functions of lncRNA based on coding
      noncoding gene co-expression network. In this network, a node (circle) represents
      the protein-coding gene or lncRNA, and an edge (connecting line between nodes)
      indicates that the two genes are co-expressed (the correlation coefficients of
      connected genes reached the defined cutoff). In this chapter, we show how to use
      an lncRNA functional annotation pipeline to construct a co-expression network
      based on gene expression profiles in prostate cancer and how to further predict
      lncRNA functions using model-based and hub-based sub-networks. 

PMID- 25055915
TI  - MicroRNA biogenesis: dicing assay.
AB  - RNA-induced silencing complex is the cytoplasmic effector machine of the microRNA
      (miRNA) pathway and contains a single-stranded miRNA guiding it to its target
      mRNAs. The biogenesis of mature miRNAs is a regulatory process achieved by
      complex machinery composed of few protein components, among which the
      ribonuclease III Dicer plays a central role. Dicer is essential for miRNA
      maturation and catalyzes one of the rate-limiting steps of miRNA production. In
      this chapter, we describe a protocol to study the catalytic activity of Dicer in
      cell extracts by measuring their ability to process precursor RNA (pre-miRNAs)
      into functional mature miRNAs. Impairment of the miRNA biogenesis machinery due
      to loss-of-function mutations in effectors of the pathway such as Dicer has been
      demonstrated before. Dicing assay can be used in cancer to assess Dicer enzymatic
      activity compared with healthy controls. Therefore, this experimental approach is
      likely to be useful to researchers investigating the main steps of miRNA
      biogenesis and function in human health and diseases. 

PMID- 25055916
TI  - Faster experimental validation of microRNA targets using cold fusion cloning and
      a dual firefly-Renilla luciferase reporter assay.
AB  - Different target prediction algorithms have been developed to provide a list of
      candidate target genes for a given animal microRNAs (miRNAs). However, these
      computational approaches provide both false-positive and false-negative
      predictions. Therefore, the target genes of a specific miRNA identified in silico
      should be experimentally validated. In this chapter, we describe a step-by-step
      protocol for the experimental validation of a direct miRNA target using a faster
      Dual Firefly-Renilla Luciferase Reporter Assay. We describe how to construct
      reporter plasmids using the simple, fast, and highly efficient cold fusion
      cloning technology, which does not require ligase, phosphatase, or restriction
      enzymes. In addition, we provide a protocol for co-transfection of reporter
      plasmids with either miRNA mimics or miRNA inhibitors in human embryonic kidney
      293 (HEK293) cells, as well as a description on how to measure Firefly and
      Renilla luciferase activity using the Dual-Glo Luciferase Assay kit. As an
      example of the use of this technology, we will validate glucose-6-phosphate
      dehydrogenase (G6PD) as a direct target of miR-1207-5p. 

PMID- 25055917
TI  - Experimental validation of predicted mammalian microRNAs of mirtron origin.
AB  - MicroRNAs (miRNAs) are ~22 nucleotide-long noncoding RNAs influencing many
      cellular processes by their regulatory functions on gene expression. MiRNAs of
      mirtron origin represent the most prominent group of the alternatively processed
      miRNAs. They reside in short introns, which are essentially equivalent to the
      precursor form of the given miRNA. Consequently, their maturation is independent
      of the Drosha/DGCR8 complex, while depends on the mechanism of mRNA splicing. The
      number of predicted human mirtron sequences increases as a consequence of the
      growing deep sequencing data and refined bioinformatics tools. However,
      experimental validations of particular sequences are also essential. In this
      chapter, we intend to provide detailed protocols for the investigation of
      predicted mirtron sequences. First, we use the Sleeping Beauty transposon-based
      gene-delivery system for the development of cell lines stably overexpressing
      mirtrons. The processing of functional mature miRNAs is then detected by a
      luciferase assay using a very strict "triple control" system. In addition, bona
      fide mirtron features are confirmed by demonstrating splicing dependency through
      splice site mutations, while Drosha/DGCR8 independency is assessed in DGCR8
      deficient cell line. Finally, the presence of mirtron-derived mature miRNAs is
      detected by quantitative real-time PCR. 

PMID- 25055918
TI  - A guide for miRNA target prediction and analysis using web-based applications.
AB  - MiRNAs are small noncoding RNAs which act by binding to the 3'UTR of mRNA
      transcripts to exert a negative regulatory effect. The miRNA binding to its
      target follows rules based on the base complementarity of the seed sequence (2-9
      first nucleotides of the miRNA sequence). Several algorithms have been developed
      to predict miRNA binding to genomic targets and its physiological consequences.
      This chapter will describe several practical aspects for the use of miRNA target
      prediction algorithms taking advantage of their web interfaces as well as how to
      produce integrative results in a graphical manner. 

PMID- 25055919
TI  - Tapping microRNA regulation networks through integrated analysis of microRNA-mRNA
      high-throughput profiles.
AB  - Understanding the biological relevance and context of microRNA (miRNA) regulation
      of target mRNAs is difficult to ascertain because an individual miRNA aids
      simultaneously in the regulation of hundreds of mRNAs in a cell. With the
      increasing availability of large public datasets that profile both mRNA and miRNA
      expression levels from the same samples, it is possible to apply robust
      statistical methods to identify global negative correlations in miRNA and target
      mRNA expression. Using a dataset from The Cancer Genome Atlas as a case study, we
      show how to use linear regression analysis followed by permutation-based false
      discovery rate to assign high statistical power to pair-wise negative
      correlations of miRNA and mRNA expression. Used in conjunction with available
      prediction tools or other target databases, a high confidence dataset of global
      miRNA-mRNA interactions can be generated. We also describe further methods to
      prioritize identified interactions by integrating with mutation, copy number
      variation, methylation, or survival data to support observations and provide
      context. Finally, we discuss methods to experimentally validate selected novel
      targets. 

PMID- 25055920
TI  - miRWalk database for miRNA-target interactions.
AB  - miRWalk (http://mirwalk.uni-hd.de/) is a publicly available comprehensive
      resource, hosting the predicted as well as the experimentally validated microRNA
      (miRNA)-target interaction pairs. This database allows obtaining the possible
      miRNA-binding site predictions within the complete sequence of all known genes of
      three genomes (human, mouse, and rat). Moreover, it also integrates many novel
      features such as a comparative platform of miRNA-binding sites resulting from ten
      different prediction datasets, a holistic view of genetic networks of miRNA-gene
      pathway, and miRNA-gene-Online Mendelian Inheritance in Man disorder
      interactions, and unique experimentally validated information (e.g., cell lines,
      diseases, miRNA processing proteins). In this chapter, we describe a schematic
      workflow on how one can access the stored information from miRWalk and
      subsequently summarize its applications. 

PMID- 25055921
TI  - A schematic workflow for collecting information about the interaction between
      copy number variants and microRNAs using existing resources.
AB  - MicroRNAs (miRNAs) and copy number variations (CNVs) are two extensively studied
      genomic components in the field of modern biology-as they have been found to be
      associated with many disorders such as cancer, Alzheimer, pancreatitis, HIV
      susceptibility, beta-thalassemia, and glomerulonephritis. Several studies
      suggested that an alteration in CNV-miRNA interaction could result in some human
      diseases such as cancer. Therefore, the possible miRNA-binding site information
      within the CNV genes opens new avenues in understanding such disorders. In this
      chapter, we present a schematic approach for collecting the information on CNV
      miRNA interactions using miRWalk and TargetScan databases. 

PMID- 25055922
TI  - SYBR(r) Green and TaqMan(r) quantitative PCR arrays: expression profile of genes
      relevant to a pathway or a disease state.
AB  - Quantitative PCR arrays are the most reliable and accurate tool for analyzing the
      expression of a focused panel of genes relevant to a pathway or a disease state.
      PCR arrays allow gene expression analysis with the sensitivity, dynamic range,
      and specificity of a real-time PCR as well as the multi-gene profiling capability
      of a microarray. Differences among real-time PCR kits used in PCR arrays are
      largely restricted to the DNA polymerases and the detection methods used. In this
      chapter, we provide a step-by-step protocol for the two detection methods most
      commonly used in PCR arrays, known as SYBR((r)) Green and TaqMan((r)), which are
      based on two different approaches to detect PCR products. While SYBR((r)) Green
      uses a binding dye that intercalates nonspecifically into double-stranded DNA,
      the TaqMan((r)) approach relies on a fluorogenic oligonucleotide probe that binds
      only the DNA sequence between the two PCR primers. Therefore, only specific PCR
      product can generate a fluorescent signal in TaqMan((r)) PCR. Here we also
      provide a comparison of the SYBR((r)) Green and TaqMan((r)) approaches and
      highlight their advantages and disadvantages to help the user to choose the best
      platform. 

PMID- 25055923
TI  - Comprehensive meta-analysis of microRNA expression using a robust rank
      aggregation approach.
AB  - Differential microRNA (miRNA) expression profiling by high-throughput methods has
      generated a vast amount of information about the complex role of these small
      regulatory molecules in a broad spectrum of human diseases. However, the results
      of such studies are often inconsistent, mostly due to the lack of cross-platform
      standardization, ongoing discovery of novel miRNAs, and small sample size.
      Therefore, a critical and systematic analysis of all available information is
      essential for successful identification of the most relevant miRNAs. Meta
      analysis approach allows integrating the results from several independent studies
      in order to achieve greater statistical power and estimate the variability
      between the studies. Here we describe as an example the use of a robust rank
      aggregation (RRA) method for identification of miRNA meta-signature in lung
      cancer. This method analyzes prioritized gene lists and finds commonly
      overlapping genes, which are ranked consistently better than expected by chance.
      An RRA approach not only helps to prioritize the putative targets for further
      experimental studies but also highlights the challenges related with the
      development of miRNA-based tests and emphasizes the need for rigorous evaluation
      of the results before proceeding to clinical trials. 

PMID- 25055924
TI  - An RT distribution analysis of relatedness proportion effects in lexical decision
      and semantic categorization reveals different mechanisms.
AB  - The magnitude of the semantic priming effect is known to increase as the
      proportion of related prime-target pairs in an experiment increases. This
      relatedness proportion (RP) effect was studied in a lexical decision task at a
      short prime-target stimulus onset asynchrony (240 ms), which is widely assumed to
      preclude strategic prospective usage of the prime. The analysis of the reaction
      time (RT) distribution suggested that the observed RP effect reflected a
      modulation of a retrospective semantic matching process. The pattern of the RP
      effect on the RT distribution found here is contrasted to that reported in De Wit
      and Kinoshita's (2014) semantic categorization study, and it is concluded that
      the RP effect is driven by different underlying mechanisms in lexical decision
      and semantic categorization. 

PMID- 25055925
TI  - Age-related decrease of the phosphorus content in the ligamentum capitis femoris
      of monkeys.
AB  - To elucidate compositional changes of the ligament with aging, the authors
      investigated age-related changes of elements in the ligamentum capitis femoris
      (LCF) of monkeys with a wide range of ages by direct chemical analysis. Used
      rhesus and Japanese monkeys consisted of 9 males and 22 females, ranging in age
      from newborn to 31 years (average age = 10.4 +/- 10.9 years). After incineration
      with nitric acid and perchloric acid, element contents were determined by
      inductively coupled plasma-atomic emission spectrometry. It was found that the P
      content decreased significantly in the LCFs of monkeys with aging, but other six
      element contents, Ca, S, Mg, Zn, Fe, and Na, did not change significantly with
      aging. Assuming that the P content indicated the active cell density and the S
      content indicated the protein amount, an age-related change of the mass ratio of
      P/S was examined in the LCFs. The mass ratio of P/S decreased significantly in
      the LCFs in childhood. Regarding the relationships among elements, significant
      direct correlations were found among the Ca, P, S, and Mg contents in the LCFs.
      It was suggested that the active cell density of the connective tissue cells
      might decrease significantly in the LCF in childhood.

PMID- 25055926
TI  - Effects of resistance exercise on iron absorption and balance in iron-deficient
      rats.
AB  - We have previously reported that resistance exercise improved the iron status in
      iron-deficient rats. The current study investigated the mechanisms underlying
      this exercise-related effect. Male 4-week-old rats were divided into a group
      sacrificed at the start (week 0) (n = 7), a group maintained sedentary for 6
      weeks (S) or a group that performed exercise for 6 weeks (E), and all rats in the
      latter groups were fed an iron-deficient diet (12 mg iron/kg) for 6 weeks. The
      rats in the E group performed climbing exercise (5 min * 6 sets/day, 3
      days/week). Compared to the week 0 rats, the rats in the S and E groups showed
      lower tissue iron content, and the hematocrit, hemoglobin, plasma iron, and
      transferrin saturation values were all low. However, the tissue iron content and
      blood iron status parameters, and the whole body iron content measured using the
      whole body homogenates of the rats, did not differ between the S group and the E
      group. The messenger RNA (mRNA) expression levels of hepcidin, duodenal
      cytochrome b, divalent metal transporter 1, and ferroportin 1 did not differ
      between the S group and the E group. The apparent absorption of iron was
      significantly lower in the E group than in the S group. Therefore, it was
      concluded that resistance exercise decreases iron absorption, whereas the whole
      body iron content is not affected, and an increase in iron recycling in the body
      seems to be responsible for this effect.

PMID- 25055927
TI  - Roles of horseradish peroxidase in response to terbium stress.
AB  - The pollution of the environment by rare earth elements (REEs) causes deleterious
      effects on plants. Peroxidase plays important roles in plant response to various
      environmental stresses. Here, to further understand the overall roles of
      peroxidase in response to REE stress, the effects of the REE terbium ion (Tb(3+))
      on the peroxidase activity and H2O2 and lignin contents in the leaves and roots
      of horseradish during different growth stages were simultaneously investigated.
      The results showed that after 24 and 48 h of Tb(3+) treatment, the peroxidase
      activity in horseradish leaves decreased, while the H2O2 and lignin contents
      increased. After a long-term (8 and 16 days) treatment with Tb(3+), these effects
      were also observed in the roots. The analysis of the changes in peroxidase
      activity and H2O2 and lignin contents revealed that peroxidase plays important
      roles in not only reactive oxygen species scavenging but also cell wall
      lignification in horseradish under Tb(3+) stress. These roles were closely
      related to the dose of Tb(3+), duration of stress, and growth stages of
      horseradish.

PMID- 25055928
TI  - Enhanced antiviral treatment efficacy and uptake in preventing the rising burden
      of hepatitis C-related liver disease and costs in Australia.
AB  - BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is an important
      cause of advanced liver disease and liver-related deaths in Australia. Our aim
      was to describe the burden of HCV infection and consider treatment strategies to
      reduce HCV-related morbidity and mortality. METHODS: Baseline model parameters
      were based upon literature review and expert consensus with a focus on Australian
      data. Three treatment scenarios based on anticipated introduction of improved
      direct-acting antiviral regimens were considered to reduce HCV disease burden.
      Scenario 1 evaluated the impact of increased treatment efficacy alone (to 80-90%
      by 2016). Scenario 2 evaluated increased efficacy and increased treatment uptake
      (2550 to 13,500 by 2018) without treatment restriction, while Scenario 3
      considered the same increases with treatment limited to >= F3 during 2015-2017.
      RESULTS: In 2013, there were an estimated 233,490 people with chronic HCV
      infection: 13,850 with cirrhosis, 590 with hepatocellular carcinoma (HCC) and 530
      liver-related deaths. If the current HCV treatment setting is unchanged,
      threefold increases in the number of people with cirrhosis, HCC, and liver
      disease deaths will be seen by 2030. Scenario 1 resulted in modest impacts on
      disease burden (4% decrease in HCC, decompensated cirrhosis, and liver deaths)
      and costs. Scenario 3 had the greatest impact on disease burden (approximately
      50% decrease in HCC, decompensated cirrhosis, and liver deaths) and costs, while
      Scenario 2 had slightly lesser impact. CONCLUSIONS: Considerable increases in the
      burden of HCV-related advanced liver disease and its complications will be seen
      in Australia under current treatment levels and outcomes. Introduction of
      improved direct-acting antiviral regimens with enhanced efficacy at current
      treatment levels will lead to limited impacts on this disease burden. A
      combination of increased treatment efficacy and greater uptake is required to
      achieve major reductions in advanced liver disease and related costs.

PMID- 25055929
TI  - Should we be "quarantining" students for Objective Structured Clinical
      Examinations (OSCEs)?

PMID- 25055930
TI  - Children and adults both see 'pirates' in 'parties': letter-position effects for
      developing readers and skilled adult readers.
AB  - Developing readers often make anagrammatical errors (e.g. misreading pirates as
      parties), suggesting they use letter position flexibly during word recognition.
      However, while it is widely assumed that the occurrence of these errors decreases
      with increases in reading skill, empirical evidence to support this distinction
      is lacking. Accordingly, we compared the performance of developing child readers
      (aged 8-10 years) against the end-state performance of skilled adult readers in a
      timed naming task, employing anagrams used previously in this area of research.
      Moreover, to explore the use of letter position by developing readers and skilled
      adult readers more fully, we used anagrams which, to form another word, required
      letter transpositions over only interior letter positions, or both interior and
      exterior letter positions. The patterns of effects across these two anagram types
      for the two groups of readers were very similar. In particular, both groups
      showed similarly slowed response times (and developing readers increased errors)
      for anagrams requiring only interior letter transpositions but not for anagrams
      that required exterior letter transpositions. This similarity in the naming
      performance of developing readers and skilled adult readers suggests that the end
      state skilled use of letter position is established earlier during reading
      development than is widely assumed.

PMID- 25055931
TI  - An atresia cervix removal, lower uterine segment substitute for cervix and
      uterovaginal anastomosis: a case report and literature review.
AB  - PURPOSE: The management of cervical dysgenesis is still a big challenge, mostly
      due to the complexity of the malformation and the difficulty to conserve the
      patient's fertility during the surgery. The objective of this article is to
      report a new successful approach for treating cervical dysgenesis as well as
      conserving patients' fertility. MATERIALS AND METHODS: We presented a case of a
      22-year-old girl with vaginal agenesis and cervical dysgenesis, who after an
      initial failure at reconstructive surgery was successfully treated by removing a
      cord-like cervix and a central muscular cylinder of her lower uterine segment and
      lining the channel with peritoneum as the reconstructed cervix. RESULTS: The
      patient has had normal menstruation without dysmenorrhea for one and a half years
      since the surgery. CONCLUSIONS: Several steps should be followed in managing
      patients with congenital cervical atresia: (1) a sufficient imaging evaluation
      before operation is necessary; (2) a falling-off-proof cervical catheter such as
      a mushroom catheter (also referred to as pezzers self-retaining catheter), and a
      proper vaginoplasty are key to a successful cervical canalization; (3) smooth
      grafted tissues such as peritoneum can be used to line the cervical canal to
      avoid adhesions.

PMID- 25055932
TI  - Association of calcitonin receptor gene polymorphism with bone mineral density in
      postmenopausal Chinese women: a meta-analysis.
AB  - BACKGROUND: The relationship between Calcitonin receptor (CTR) gene polymorphism
      C1377T and bone mineral density (BMD) in postmenopausal women has been studied to
      some degree in Western countries, but the reports remain inconclusive and have
      not been generalized to other populations. PURPOSE: To evaluate the association
      of CTR gene polymorphism C1377T with BMD in the Han Chinese population. METHODS:
      We searched for all published articles indexed in MEDLINE (1950-2014), EMBASE
      (1974-2014), China National Knowledge Infrastructure (CNKI, 1994-2014), and the
      Wanfang Database, using the key words "polymorphism," "CTR," "osteoporosis," and
      "bone density." The data were extracted independently by two reviewers. The
      heterogeneity between studies was determined using the Chi-square-based Q test.
      Potential publication bias was estimated using a funnel plot and Egger's linear
      regression test. Odds ratios and 95 % confidence intervals (CI) were used to
      evaluate the results. RESULTS: Six eligible studies were selected for the meta
      analysis. Our analysis suggested that the C1377T polymorphism of the CTR gene was
      associated with BMD at the lumbar spine (95 % CI -0.57 to -0.05; P = 0.02), but
      not associated with BMD at the femoral neck (95 % CI -0.27 to 0.24; P = 0.90) in
      the postmenopausal Han Chinese population. CONCLUSION: The C1377T polymorphism in
      the CTR gene is associated with BMD at the lumbar spine in a postmenopausal Han
      Chinese population and the CTR gene may become a useful genetic marker for
      predicting the risk of developing osteoporosis in postmenopausal Chinese women.

PMID- 25055933
TI  - Comparison of efficacy and safety of sublingual misoprostol with intracervical
      dinoprostone gel for cervical ripening in prelabour rupture of membranes after 34
      weeks of gestation.
AB  - PURPOSE: To compare the efficacy and safety of sublingual misoprostol with
      intracervical dinoprostone gel for cervical ripening in prelabour rupture of
      membrane after 34 weeks of gestation. METHODS: One eighty-eight women having >34
      weeks of gestation with PROM, singleton viable fetus and no prior caesarean
      section were randomized to sublingual misoprostol (50 MUg every 4 h and maximum
      of 3 doses) and intracervical dinoprostone (0.5 mg every 2 h and maximum of 2
      doses). Oxytocin augmentation was commenced in those with a satisfactory Bishop
      score, inadequate contractions and who did not go into spontaneous active labour.
      Primary outcome measures were induction-delivery interval and the number of women
      that went into spontaneous labour without oxytocin augmentation. RESULTS: There
      was a significant reduction in induction to delivery interval in sublingual
      misoprostol group compared to intracervical dinoprostone (8.3 +/- 3.6 h vs 12.2
      +/- 6.6 h; p = 0.000). There was a significant reduction in duration of rupture
      of membrane to delivery interval (p = 0.015), 1st stage of labour (p = 0.000) in
      sublingual misoprostol group as compared to the intravaginal dinoprostone group.
      There was no difference observed in spontaneous vaginal delivery between the
      groups (0.919). Oxytocin requirement was significantly higher in the dinoprostone
      group p = 0.006). There were more maternal adverse effects of sublingual
      misoprostol (p = 0.026). However, maternal and neonatal safety profiles were
      comparable. CONCLUSIONS: Sublingual misoprostol and intracervical dinoprostone at
      the dose studied are equally efficacious in achieving spontaneous vaginal
      delivery, reduction in induction-delivery interval and in reducing the need for
      oxytocin, in women after 34 weeks gestation with rupture of membranes.

PMID- 25055934
TI  - Determining the mechanisms of lapatinib-induced diarrhoea using a rat model.
AB  - INTRODUCTION: Diarrhoea caused by treatment with receptor tyrosine kinase
      inhibitors (TKI) targeting Epidermal Growth Factor Receptors (EGFR) is an
      important clinical toxicity in oncology that remains poorly understood. This
      study aimed to identify histological and molecular changes within the intestine
      following lapatinib to elucidate mechanisms of diarrhoea related to treatment
      with this dual EGFR TKI. METHODS AND MATERIALS: Male albino Wistar rats were
      orally gavaged lapatinib at 100, 240 or 500 mg/kg daily for 4 weeks and assessed
      for indicators of gastrointestinal injury at the end of each week. Lapatinib in
      combination with weekly paclitaxel (9 mg/kg i.p.) was also assessed for
      cumulative injury. At each time point, blood was collected for biochemical
      analysis. Sections or jejunum and colon were also collected and underwent
      immunohistochemistry and RT-PCR to detect markers of EGFR pathway signalling, and
      morphometric analysis to assess changes in mucosal architecture. RESULTS:
      Lapatinib (with or without paclitaxel co-treatment) caused dose-dependent changes
      in crypt length, mitotic rate and goblet cell morphology. Jejunal crypt
      expression of EGFR and ErbB2 were decreased, whilst no changes in Erk1/2 were
      observed. Markers of apoptosis (caspase-3) and proliferation (Ki-67) were only
      significantly altered in rats treated with both lapatinib and paclitaxel.
      CONCLUSIONS: In our novel rat model of lapatinib-induced diarrhoea we have shown
      that changes in small intestinal morphometry and expression of EGFR are
      associated with diarrhoea. Further research is required to test intervention
      agents for the prevention of diarrhoea.

PMID- 25055935
TI  - Risk and outcomes of chemotherapy-induced diarrhea (CID) among patients with
      colorectal cancer receiving multi-cycle chemotherapy.
AB  - BACKGROUND: Diarrhea is a common toxicity of chemotherapy, but the practice of
      reporting only severe grades (>= 3) in clinical trials results in misleading
      conclusions of significance. Epidemiology remains poorly described, and effects
      of multi-cycle regimens have not been investigated. To better understand the
      risks, symptom burden and consequences of CID, we studied patients receiving
      chemotherapy for colorectal cancer (CRC). METHODS: One hundred and fourteen
      patients receiving FOLFOX (95 patients, 530 cycles), FOLFOX + monoclonal
      antibodies (10 patients, 49 cycles) or FOLFIRI (9 patients, 50 cycles) were
      enrolled. CID was identified from diaries at baseline and daily during up to 8
      chemotherapy cycles using supplemental questions on the Oral Mucositis Daily
      Questionnaire, a valid tool for collecting patient-reported outcomes of regimen
      related mucosal injury. Patients scored CID severity from 0 "none" to 10 "worst
      possible," and quantity from "little" to "severe" on a 5-point scale. Quality of
      life was measured using the FACT-G, and fatigue using the FACIT fatigue scale.
      RESULTS: CID occurred in 89% of patients on FOLFIRI, 50% on FOLFOX + monoclonal
      antibodies and 56% on FOLFOX alone. The risk of a first episode was highest
      during Cycle 1 (35 %) and dropped to <10% during Cycles 3-5. Patients with CID
      reported poorer quality of life scores than those without CID (77.1 vs 80.7).
      CONCLUSIONS: Diarrhea occurs more commonly than typically appreciated during
      chemotherapy for CRC. Risk is highest during first exposure, suggesting variable
      susceptibility. Identification of this high-risk subgroup for prophylaxis could
      improve the quality of life.

PMID- 25055936
TI  - Liposomal anthracycline chemotherapy and the risk of second malignancies in
      patients with Kaposi's sarcoma (KS).
AB  - PURPOSE: People living with HIV (PLWH) are at increased risk of cancer, both non
      AIDS- and AIDS-defining malignancies (NADM and ADM). Systemic chemotherapy also
      predisposes to secondary cancers. The potential contribution of systemic
      liposomal anthracycline chemotherapy (SLAC) to the development of second cancers
      in PLWH is unknown. METHODS: Since 1998, we have treated 495 PLWH and Kaposi's
      sarcoma (KS) with a stage-stratified approach including 163 who received SLAC as
      first-line treatment for KS. Subsequent ADM and NADM diagnosed in this population
      were recorded. RESULTS: More patients who received SLAC had T1 stage disease (p <
      0.0001) and lower CD4 cell counts (p < 0.0001) in line with the stage-stratified
      treatment, but there were no significant differences in age (p = 0.29), gender (p
      = 0.18), prior AIDS-defining illness (p = 0.45), plasma HIV viral load (p =
      0.15), or HHV8 viral load (p = 0.39) between the two groups. During a median
      follow-up of 4.6 years (maximum 15 years) from KS diagnosis, 28 patients
      developed a second cancer (5 ADM and 23 NADM). The 5-year cumulative risk of
      second cancer is 5.8 % (95 % CI 3.0-8.6 %), and there is no significant
      difference in the rate between those treated with SLAC and those not (log rank p
      = 0.19). Most patients (n = 131) were treated with daunoxome (liposomal
      daunorubicin) chemotherapy, and there was no significant correlation between risk
      of second cancer and cumulative dose of daunoxome (p = 0.23). CONCLUSION:
      Although the risk of second cancer after a diagnosis of KS in PLWH is high,
      systemic liposomal anthracycline chemotherapy does not appear to increase the
      risk.

PMID- 25055937
TI  - Pharmacogenetics of adjuvant breast cancer treatment with cyclophosphamide,
      epirubicin and 5-fluorouracil.
AB  - PURPOSE: Most adjuvant breast cancer treatment regimens include the combination
      of an anthracycline (epirubicin or doxorubicin) and the alkylating agent
      cyclophosphamide. This study sought to investigate the influence of
      pharmacogenetics on the pharmacokinetics and metabolism of these agents. METHODS:
      Blood samples were taken from patients treated with cyclophosphamide (n = 51) and
      epirubicin (n = 35), with or without 5-fluorouracil (5-FU). The pharmacokinetics
      and metabolism of the three drugs were investigated, together with
      pharmacogenetic investigations for cyclophosphamide and epirubicin.
      Cyclophosphamide and its metabolites and also epirubicin and epirubicinol were
      measured in plasma. DNA was extracted from whole blood and genotyping performed
      using RT-PCR. RESULTS: Patients with at least one variant CYP2C19*17 allele had a
      longer CP half-life (p = 0.007), as did homozygous variants for the CYP2B6*6
      allele. There was no significant effect of GSTP1, CYP2B6*2, CYP2B6*5 or CYP2C19*2
      on any pharmacokinetic parameter of CP. An NQO2 exonic SNP was associated with a
      higher exposure to epirubicinol relative to epirubicin (p = 0.011). Other
      polymorphic variants of NQO1, carbonyl reductase, UGT enzymes and transporters
      had no influence on epirubicin or its metabolite. CONCLUSION: Overall,
      pharmacogenetic factors had only a minor influence on cyclophosphamide or
      anthracycline-based adjuvant therapy of breast cancer.

PMID- 25055939
TI  - Erratum.

PMID- 25055938
TI  - Tamoxifen plus tegafur-uracil (TUFT) versus tamoxifen plus Adriamycin
      (doxorubicin) and cyclophosphamide (ACT) as adjuvant therapy to treat node
      positive premenopausal breast cancer (PreMBC): results of Japan Clinical Oncology
      Group Study 9404.
AB  - PURPOSE: A prospective randomized clinical trial was conducted to evaluate the
      efficacy of tamoxifen plus doxorubicin and cyclophosphamide compared to tamoxifen
      plus tegafur-uracil as an adjuvant therapy to treat node-positive premenopausal
      breast cancer (PreMBC). METHODS: Eligibility criteria included pathologically
      node-positive (n = 1-9) preMBC with curative resection, in stages I-IIIA.
      Patients were randomized to receive either tamoxifen 20 mg/day plus tegafur
      uracil 400 mg/day (TU) for 2 years or six courses of a 28-day cycle of
      doxorubicin 40 mg/m(2) plus cyclophosphamide 500 mg/m(2) on day 1 along with
      tamoxifen (ACT) given for 2 years as adjuvant therapy. Primary endpoint was
      overall survival (OS), and secondary endpoint was recurrence-free survival (RFS).
      RESULTS: In total, 169 patients were recruited (TU arm 87, ACT arm 82) between
      October 1994 and September 1999. The HR for OS was 0.76 (95 % CI 0.35, 1.66, log
      rank p = 0.49) and that for RFS was 0.77 (95 % CI 0.44, 1.36, log-rank p = 0.37),
      with ACT resulting in a better HR. The 5-year OS was 79.7 % for patients in the
      TU arm and 83 % for those in the ACT arm. The 5-year RFS was 66.1 % for patients
      in the TU arm and 70.6 % for those in the ACT arm. A higher proportion of
      patients in the ACT arm experienced grade 3 leucopenia (0 % in the TU arm, 4 % in
      the ACT arm). CONCLUSIONS: There were no significant differences in the efficacy
      of TU and ACT as adjuvant therapy.

PMID- 25055940
TI  - Defining viral species: making taxonomy useful.
AB  - Virus taxonomy at present is best characterized as a categorization of
      convenience, without a firm basis in the principles of evolutionary biology.
      Specifically, virus species definitions appear to depend more on tradition and
      popular opinion among virologists than on firm, quantitative biological evidence.
      I suggest a series of changes to underlying species concepts that would shift the
      field from one that simply files viruses away in taxonomic boxes to one that can
      learn important biological lessons from its taxonomy. 

PMID- 25055941
TI  - Extreme early-life anxiety is associated with an evolutionarily conserved
      reduction in the strength of intrinsic functional connectivity between the
      dorsolateral prefrontal cortex and the central nucleus of the amygdala.

PMID- 25055943
TI  - Scan parameters and the diffusion emphasis effect in diffusion-weighted imaging
      using a motion-probing gradient preparation pulse.
AB  - Diffusion-sensitized driven equilibrium preparation (DSDE) is a gradient echo
      (GRE) diffusion-weighted imaging (DWI) sequence that employs a motion-probing
      gradient (MPG) preparation pulse and phase cycling. In DSDE, several scan
      parameters of the MPG preparation pulse and the GRE sequence affect diffusion
      sensitivity. Our investigation of the relationship between these scan parameters
      and the diffusion emphasis effect revealed the importance of "prep.TE" in the MPG
      preparation pulse and "TFE shot interval" in the gradient echo sequence.
      Appropriate choice of these parameters allows DSDE to provide a similar DWI to
      that of conventional single-shot SEEPI DWI. We therefore concluded DSDE to be a
      useful DWI method.

PMID- 25055944
TI  - Radiation dose evaluation in 3D rotation angiography and cone-beam computed
      tomography with a flat panel detector.
AB  - The aim of this study was to evaluate radiation dose in patients undergoing three
      dimensional rotation angiography (3DRA) and cone-beam computed tomography (CBCT)
      using a flat panel detector (FPD). Radiation doses were measured for angiography
      equipment using small silicon-photodiode dosimeters that were implanted in
      various positions in tissues and organs within an anthropomorphic phantom of a
      standard Japanese adult male. Output signals from the dosimeters were read out on
      a computer, from which organ and effective doses were calculated according to
      guidelines published in International Commission on Radiological Protection
      Publication 103. Lens doses and effective doses obtained in this study were 1.6
      mGy and 0.13 mSv for 3DRA, 20 mGy and 1.7 mSv for CBCT (normal mode). 3DRA
      provided substantial lens doses and effective dose reduction, which were 8% of
      the doses in CBCT (normal mode).

PMID- 25055945
TI  - Investigation of measurement accuracy of factors used for detective quantum
      efficiency measurement in digital radiography.
AB  - In the detective quantum efficiency (DQE) evaluation of detectors for digital
      radiography (DR) systems, physical image quality indices such as modulation
      transfer function (MTF) and normalized noise power spectrum (NNPS) need to be
      accurately measured to obtain highly accurate DQE evaluations. However, there is
      a risk of errors in these measurements. In this study, we focused on error
      factors that should be considered in measurements using clinical DR systems. We
      compared the incident photon numbers indicated in IEC 62220-1 with those
      estimated using a Monte Carlo simulation based on X-ray energy spectra measured
      employing four DR systems. For NNPS, influences of X-ray intensity non
      uniformity, tube voltage and aluminum purity were investigated. The effects of
      geometric magnifications on MTF accuracy were also examined using a tungsten edge
      plate at distances of 50, 100 and 150 mm from the detector surface at a source
      image receptor distance of 2000 mm. The photon numbers in IEC 62220-1 coincided
      with our estimates of values, with error rates below 2.5%. Tube voltage errors of
      approximately +/-5 kV caused NNPS errors of within 1.0%. The X-ray intensity non
      uniformity caused NNPS errors of up to 2.0% at the anode side. Aluminum purity
      did not affect the measurement accuracy. The maximum MTF reductions caused by
      geometric magnifications were 3.67% for 1.0-mm X-ray focus and 1.83% for 0.6-mm X
      ray focus.

PMID- 25055946
TI  - Optimization of reconstruction parameters using a multi-focus fan beam collimator
      in myocardial perfusion single photon emission computed tomography study.
AB  - PURPOSE: The aim of this study was to optimize the reconstruction parameters for
      ordered subset conjugate gradient minimization (OSCGM) reconstruction using a
      multifocus fan beam collimator in myocardial perfusion single photon emission
      computed tomography (SPECT). METHOD: We attempted to validate the following
      performance of OSCGM reconstruction parameters (iteration and subset). SPECT
      images were acquired using a dual-head gamma camera with IQ mode acquisition
      systems from a RH-2 cardiac phantom containing a 99m-Tc solution. The performance
      was evaluated using reconstruction parameters (product of subset and iteration:
      SI) with image contrast, LV volume [using quantitative perfusion SPECT (QPS)],
      root mean square uncertainty (RMSU), and normalized mean squared error (NMSE).
      RESULTS: The best results (contrast, uniformity, LV volume, and NMSE) were found
      for SI: 30. LV volume indicated the true volume for subset: 1 and iteration: 30,
      and LV volume was underestimated by 10% for iteration >20, and subset >1.
      CONCLUSION: The results of this myocardial perfusion SPECT study suggest the
      optimal OSCGM reconstruction parameter to be subset: 1 and iteration: 30 using a
      multifocus fan beam collimator.

PMID- 25055947
TI  - Visualization of the foramen intervertebral nerve root of cervical spine with 3.0
      tesla magnetic resonance imaging: a comparison of three-dimensional acquisition
      techniques.
AB  - Identification of the compression factor in cervical disc herniation and cervical
      spondylotic radioculopathy is often problematic when using two-dimensional
      magnetic resonance imaging (MRI). This prompted us to compare and examined three
      dimensional sequences, coherent oscillatory state acquisition for the
      manipulation of image contrast (COSMIC), fast imaging employing steady state
      acquisition (FIESTA) and T2 star weighted MR angiography (SWAN) with 3.0-Tesla
      (T) MRI to visualize the foramen intervertebral nerve root for the cervical
      spine. Fat-suppressed COSMIC (FS-COSMIC) sequence gave the highest signal
      intensity ratio (1.85 +/- 0.06) of the nerve root and vertebral arch. A
      significant difference in signal intensity ratio of the nerve root was found
      between FS-COSMIC and FIESTA sequences. No significant difference was found
      between the FS-COSMIC and FIESTA sequences in the cerebrospinal fluid and the
      spinal cord. The FS-COSMIC sequence proved to be the most suitable sequence for
      intra and extra dura matter.

PMID- 25055948
TI  - Experience of low volume split-dose bowel preparation for computed tomography
      colonography.
AB  - We propose a new preparation method for the computed tomography colonography
      (CTC). This method consists of giving a small volume (400 ml) of cleansing
      solution on the day before the examination and the same volume of solution on the
      day of the examination [low volume split-dose (LVSD) method]. Using this method,
      we compared the volume of residual fluid in the colon, the CT value of the
      residual fluid, and the quality of stool tagging with those for patients
      undergoing the conventional bowel preparation method. Polyp detectability of the
      CTC using this method and the acceptability of the preparation were also
      investigated. The volume of residual fluid in the colon with this method was
      smaller than that with the conventional method. The CT value of the residual
      fluid with this method was higher than that with the conventional method. Visual
      assessment of the quality of stool tagging with this method gave similar results
      to those obtained using the conventional method. The sensitivities were 95% for 5
      10 mm polyps and 100% for polyps larger than 10 mm. The PPVs were 91% for 5-10 mm
      polyps and 100% for polyps larger than 10 mm. These results appear to be as good
      as in previous reports. In the questionnaires, about 80% of the answers were
      favorable regarding the volume and the taste of laxative. We conclude that LVSD
      bowel preparation method for CTC maintains polyp detectability and is better
      tolerated.

PMID- 25055949
TI  - Photon mass energy transfer coefficients for elements z=1 to 92 and 48 additional
      substances of dosimetric interest.
AB  - Photon mass energy transfer coefficient is an essential factor when converting
      photon energy fluence into kinetic energy released per unit mass (kerma).
      Although mass attenuation coefficient and mass energy absorption coefficients can
      be looked up in databases, the mass energy transfer coefficient values are still
      controversial. In this paper, the photon mass energy transfer coefficients for
      elements Z=1-92 were calculated based on cross-sectional data for each photon
      interaction type. Mass energy transfer coefficients for 48 compounds and/or
      mixtures of dosimetric interest were calculated from coefficient data for
      elements using Bragg's additivity rule. We additionally developed software that
      can search these coefficient data for any element or substance of dosimetric
      interest. The database and software created in this paper should prove useful for
      radiation measurements and/or dose calculations.

PMID- 25055950
TI  - Changes in X-ray computed tomography imaging technology and JSRT journal papers
      from conventional computed tomography to volume computed tomography, toward
      further development-.

PMID- 25055951
TI  - 2. Monte Carlo method and simulation.

PMID- 25055952
TI  - 4. Clinical application 2: iterative image reconstruction for x-ray computed
      tomography.

PMID- 25055954
TI  - Introduction of the economical evaluation's department and its activities at
      JIRA.

PMID- 25055953
TI  - 1. Diseases of the brain 1: cerebrovascular diseases.

PMID- 25055955
TI  - Current status of series on radiological technology.

PMID- 25055956
TI  - Photophysical properties of an unusual bichromophoric species constructed from a
      cyclometalated Pt(II) chromophore and a blue Bodipy-acetylacetonate species.
AB  - A Bodipy species bearing an acetyl-acetonate (acac) group, , has been prepared
      from a blue absorbing borondipyrromethene core bearing gallate substituted
      paraffin chains. Compound chelates a Pt(ii) center having an orthometalated 2
      phenyl-pyridine anion (ppy) as an additional ligand, giving rise to a new
      bichromophoric Pt(ii)-Bodipy species, . The absorption spectra, redox behavior
      and photophysical properties of , and of the neutral Pt(ii) compound , containing
      ppy and an acac derivative as ligands, have been studied. Compounds and are used
      as models for the Bodipy-based and the metal-based subunits of , respectively.
      The (3)LC emission of is fully quenched in , whereas the Bodipy fluorescence is
      only weakly reduced in compared to , indicating weak interaction between the
      subunits. Two different charge-separated (CS) states have a role in the
      intercomponent excited state decays of . Notably, whereas in all the previously
      investigated bichromophoric metal(polypyridine)-Bodipy compounds, the light
      absorbed by the metal-based unit leads to population of the lowest-energy triplet
      Bodipy-based level, in it contributes with high efficiency (>99%) to the Bodipy
      fluorescence. An efficient and formally forbidden (3)LC to (1)Bodipy energy
      transfer occurring by Forster mechanism is, unprecedently, the dominant (3)LC
      decay process in . 

PMID- 25055957
TI  - Antimicrobial stewardship in residential aged care facilities: need and readiness
      assessment.
AB  - BACKGROUND: Information about the feasibility, barriers and facilitators of
      antimicrobial stewardship (AMS) in residential aged care facilities (RACFs) has
      been scant. Exploring the prevailing perceptions and attitudes of key healthcare
      providers towards antibiotic prescribing behaviour, antibiotic resistance and AMS
      in the RACF setting is imperative to guide AMS interventions. METHODS: Semi
      structured interviews and focus groups were conducted with key RACF healthcare
      providers until saturation of themes occurred. Participants were recruited using
      purposive and snowball sampling. The framework approach was applied for data
      analysis. RESULTS: A total of 40 nurses, 15 general practitioners (GPs) and 6
      pharmacists from 12 RACFs were recruited. Five major themes emerged; perceptions
      of current antibiotic prescribing behaviour, perceptions of antibiotic
      resistance, attitude towards and understanding of AMS, perceived barriers to and
      facilitators of AMS implementation, and feasible AMS interventions. A higher
      proportion of GPs and pharmacists compared with nurses felt there was over
      prescribing of antibiotics in the RACF setting. Antibiotic resistance was
      generally perceived as an issue for infection control rather than impacting
      clinical decisions. All key stakeholders were supportive of AMS implementation in
      RACFs; however, they recognized barriers related to workload and logistical
      issues. A range of practical AMS interventions were identified, with nursing
      based education, aged-care specific antibiotic guidelines and regular antibiotic
      surveillance deemed most useful and feasible. CONCLUSIONS: Areas of antibiotic
      over-prescribing have been identified from different healthcare providers'
      perspectives. However, concern about the clinical impact of antibiotic resistance
      was generally lacking. Importantly, information gathered about feasibility,
      barriers and facilitators of various AMS interventions will provide important
      insights to guide development of AMS programs in the RACF setting.

PMID- 25055958
TI  - Treatment-related mortality with aflibercept in cancer patients.

PMID- 25055959
TI  - Appraisal of the dopaminergic and noradrenergic innervation of the submucosal
      plexus in PD.
AB  - BACKGROUND: The principal components of the enteric nervous system (ENS) are two
      neuronal networks, the myenteric and submucosal plexus (SMP), which are primarily
      involved in the regulation of gastrointestinal (GI) motility and secretion,
      respectively. These two plexus are made up of intrinsic neurons receiving input
      from the extrinsic sympathetic and parasympathetic innervation of the gut. Both
      the intrinsic and extrinsic innervations of the gut are affected by Lewy
      pathology in Parkinson's disease (PD). A recent autopsy survey indicated that
      there was no global or dopaminergic loss in the myenteric plexus in PD but the
      SMP was not examined. OBJECTIVE: The aim of the present work was to compare the
      relative abundance of dopaminergic and noradrenergic neurons in colonic biopsies
      between PD patients and control individuals. METHODS: Colonic biopsies were taken
      during the course of a colonoscopy in 35 PD patients and 10 control subjects.
      Density of dopaminergic neurons and expression of the dopaminergic and
      noradrenergic markers were analyzed by tyrosine hydroxylase (TH)
      immunofluorescence and Western blot using anti-dopamine transporter (DAT) and
      anti-dopamine beta-hydroxylase (DBH), respectively. RESULTS: No significant
      differences were observed in the density of dopaminergic neurons and in the
      expression levels of dopaminergic and noradrenergic markers in colonic biopsies
      from PD patients as compared to controls. CONCLUSION: Our results indicate that
      there is no evidence of dopaminergic and noradrenergic neuronal loss in the SMP
      in PD, thereby suggesting that neuropathology in submucosal neurons is unlikely
      to be a causative factor for GI dysfunction in PD.

PMID- 25055960
TI  - Using ecological whole body kinematics to evaluate effects of medication
      adjustment in Parkinson disease.
AB  - BACKGROUND: Functional motor impairments including mobility are major reasons for
      clinical intervention and medication adjustment in symptomatic therapy for
      Parkinson's disease (PD). Outcome measures used to assess the impact of
      medication are mostly based on patients' memory or diaries which, considering the
      gaps between visits, are neither objective nor very reliable. OBJECTIVE:
      Investigating the feasibility of using movement features extracted from
      ecological whole-body kinematics recordings to measure the quantitative and
      qualitative changes in multiple aspects of mobility after medication changes in
      PD. METHODS: Eleven patients with PD (PwPD) performed mobility tasks in their own
      home, wearing a full body wireless inertial sensing based motion capture system.
      Three scripted walking tasks (walking, fast walking, and walk turns) were
      examined at baseline and two weeks after medication changes. Clinical scales,
      including investigator-rated clinical global impression of improvement (CGI-I),
      were collected at both visits. RESULTS: Out of 59 recorded body joint variables,
      five were identified as pertinent. Changes were represented in vector space as a
      plot of mean versus peak amplitude. Regression analysis was used to predict
      clinical improvement or worsening based on these vector features. The predictors
      were able to explain (>98.5% of variance) patients' clinical global impression of
      improvement, thus correctly predicting 5 cases of improvement and 2 cases of
      worsening. CONCLUSIONS: This study provided a method of extracting clinically
      meaningful reports from ecological kinematic data showing changes after drug
      adjustments. The results are presented using a novel concept called change space
      that may be more understandable for clinical staff.

PMID- 25055961
TI  - Potency of individual bile acids to regulate bile acid synthesis and transport
      genes in primary human hepatocyte cultures.
AB  - Bile acids (BAs) are known to regulate their own homeostasis, but the potency of
      individual bile acids is not known. This study examined the effects of cholic
      acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid
      (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport
      genes in human primary hepatocyte cultures. Hepatocytes were treated with the
      individual BAs at 10, 30, and 100MUM for 48 h, and RNA was extracted for real
      time PCR analysis. For the classic pathway of BA synthesis, BAs except for UDCA
      markedly suppressed CYP7A1 (70-95%), the rate-limiting enzyme of bile acid
      synthesis, but only moderately (35%) down-regulated CYP8B1 at a high
      concentration of 100MUM. BAs had minimal effects on mRNA of two enzymes of the
      alternative pathway of BA synthesis, namely CYP27A1 and CYP7B1. BAs increased the
      two major target genes of the farnesoid X receptor (FXR), namely the small
      heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth
      factor 19 (FGF19) over 100-fold. The BA uptake transporter Na(+)-taurocholate co
      transporting polypeptide was unaffected, whereas the efflux transporter bile salt
      export pump was increased 15-fold and OSTalpha/beta were increased 10-100-fold by
      BAs. The expression of the organic anion transporting polypeptide 1B3 (OATP1B3;
      sixfold), ATP-binding cassette (ABC) transporter G5 (ABCG5; sixfold), multidrug
      associated protein-2 (MRP2; twofold), and MRP3 (threefold) were also increased,
      albeit to lesser degrees. In general, CDCA was the most potent and effective BA
      in regulating these genes important for BA homeostasis, whereas DCA and CA were
      intermediate, LCA the least, and UDCA ineffective. 

PMID- 25055962
TI  - Simvastatin and dipentyl phthalate lower ex vivo testicular testosterone
      production and exhibit additive effects on testicular testosterone and gene
      expression via distinct mechanistic pathways in the fetal rat.
AB  - Sex differentiation of the male reproductive tract in mammals is driven, in part,
      by fetal androgen production. In utero, some phthalate esters (PEs) alter fetal
      Leydig cell differentiation, reducing the expression of several genes associated
      with steroid synthesis/transport, and consequently, lowering fetal androgen and
      Insl3 hormone levels. Simvastatin (SMV) is a cholesterol-lowering drug that
      directly inhibits HMG-CoA reductase. SMV may also disrupt steroid biosynthesis,
      but through a different mode of action (MOA) than the PEs. As cholesterol is a
      precursor of steroid hormone biosynthesis, we hypothesized that in utero exposure
      to SMV during the critical period of sex differentiation would lower fetal
      testicular testosterone (T) production without affecting genes involved in
      cholesterol and androgen synthesis and transport. Secondly, we hypothesized that
      a mixture of SMV and a PE, which may have different MOAs, would reduce
      testosterone levels in an additive manner. Pregnant Sprague Dawley rats were
      dosed orally with SMV, dipentyl phthalate (DPeP), or SMV plus DPeP from
      gestational days 14-18, and fetuses were evaluated on GD18. On GD18, SMV lowered
      fetal T production and serum triglycerides, low density lipoprotein, high density
      lipoprotein, and total cholesterol levels, and downregulated two genes in the
      fetal testis that were different from those altered by PEs. When SMV and DPeP
      were administered as a mixture, fetal T production was significantly reduced in
      an additive manner, thus demonstrating that a mixture of chemicals can induce
      additive effects on fetal T production even though they display different MOAs. 

PMID- 25055963
TI  - Examining the protective role of ErbB2 modulation in human-induced pluripotent
      stem cell-derived cardiomyocytes.
AB  - Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being
      used as an in vitro model system in cardiac biology and in drug discovery (e.g.,
      cardiotoxicity testing). Qualification of these cells for use in mechanistic
      investigations will require detailed evaluations of cardiomyocyte signaling
      pathways and cellular responses. ErbB signaling and the ligand neuregulin play
      critical roles in survival and functional integrity of cardiac myocytes. As such,
      we sought to characterize the expression and activity of the ErbB family of
      receptors. Antibody microarray analysis performed on cell lysates derived from
      maturing hiPSC-CMs detected expression of ~570 signaling proteins. EGFR/ErbB1,
      HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor
      receptor family were confirmed by Western blot. Activation of ErbB signaling by
      neuregulin-1beta (NRG, a natural ligand for ErbB4) and its modulation by
      trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule
      ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation
      of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using
      nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA
      silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of
      ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated
      doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real
      time cellular impedance analysis and ATP measurement. Collectively, these results
      support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and
      support the value of using these cells in early assessments of cardiotoxicity or
      efficacy. 

PMID- 25055965
TI  - Asn-Trp dipeptides improve the oxidative stress and learning dysfunctions in D
      galactose-induced BALB/c mice.
AB  - The oral administration of Asn-Trp (NW) or carnosine (beta-alanyl-L-histidine)
      dipeptides to D-galactose (Gal)-induced BALB/c mice was used to evaluate
      antioxidant activities in vivo. D-Galactose (Gal) was subcutaneously injected
      into the dorsal necks of mice daily for eight weeks to induce oxidative stress
      (Gal group). From the beginning of the fifth week, groups of NW10, NW40 (10 or 40
      mg NW kg(-1)) or carnosine40 (40 mg carnosine kg(-1)) were administered orally
      concurrent Gal injection until the end of studies. It was found that the
      malondialdehyde (MDA) contents in these intervention groups were much lower than
      the Gal group. The mice in the NW40 group showed significant improvements
      compared to the Gal group in a reference memory task and probe trial test
      evaluated by Morris water maze. Mice in the intervention groups showed higher GSH
      levels and oxygen radical antioxidant capacity activities and lower MDA levels in
      the brain or liver tissues compared to the Gal group. The levels of advanced
      glycation end-products, including N(epsilon)-(carboxymethyl)lysine (CML) and
      argpyrimidine, in the brain tissues of the NW40 interventions are significantly
      lower compared to the Gal group. These results suggest that NW may be useful in
      developing functional foods for antioxidant and anti-aging purposes.

PMID- 25055964
TI  - Toxicogenomic analysis reveals profibrogenic effects of trichloroethylene in
      autoimmune-mediated cholangitis in mice.
AB  - Epidemiological studies suggest that exposure to environmental chemicals
      increases the risk of developing autoimmune liver disease. However, the identity
      of specific chemical perpetrators and the mechanisms whereby environmental
      chemicals modify liver disease is unclear. Previous studies link exposure to
      trichloroethylene (TCE) with the development of autoimmune liver disease and
      exacerbation of autoimmunity in lupus-prone MRL mice. In this study, we utilized
      NOD.c3c4 mice, which spontaneously develop autoimmune cholangitis bearing
      resemblance to some features of primary biliary cirrhosis. Nine-week-old female
      NOD.c3c4 mice were given TCE (0.5 mg/ml) or its vehicle (1% Cremophor-EL) in
      drinking water for 4 weeks. TCE had little effect on clinical chemistry, biliary
      cyst formation, or hepatic CD3+ T-cell accumulation. Hepatic microarray profiling
      revealed a dramatic suppression of early growth response 1 (EGR1) mRNA in livers
      of TCE-treated mice, which was verified by qPCR and immunohistochemical staining.
      Consistent with a reported link between reduced EGR1 expression and liver
      fibrosis, TCE increased hepatic type I collagen (COL1A1) mRNA and protein levels
      in livers of NOD.c3c4 mice. In contrast, TCE did not increase COL1A1 expression
      in NOD.ShiLtJ mice, which do not develop autoimmune cholangitis. These results
      suggest that in the context of concurrent autoimmune liver disease with a genetic
      basis, modification of hepatic gene expression by TCE may increase profibrogenic
      signaling in the liver. Moreover, these studies suggest that NOD.c3c4 mice may be
      a novel model to study gene-environment interactions critical for the development
      of autoimmune liver disease. 

PMID- 25055966
TI  - Donor kidneys with miliary papillary renal cell neoplasia: the role of the
      pathologist in determining suitability for transplantation.
AB  - BACKGROUND: Kidneys with single or multiple tumors, provided that they have
      histological features recognized as being associated with low risk of recurrence,
      are considered suitable for transplantation. It is known that kidneys with
      multiple primary renal tumors show poor renal function and that function
      dramatically declines when tumors have a miliary configuration. Despite this, no
      guidelines are in place to differentiate between multifocal tumors and those that
      are miliary in nature. CASE REPORT: We report a case in which initial examination
      revealed papillary renal cell neoplasia in deceased donor kidneys, which were
      later confirmed on histological and genetic testing to be multiple and miliary in
      distribution. Gross examination showed closely opposed neoplasms, and on
      histological examination these were found to be papillary renal cell carcinomas
      and renal papillary adenomas. This ultimately led to the decision that both
      kidneys were unsuitable for transplantation. CONCLUSIONS: At present there are no
      recommendations as to how tumor-bearing donor kidneys should be handled in order
      to determine if miliary neoplasia is present. From our case it is apparent that,
      in addition to obvious tumor nodules, at least 3 samples of cortex should be
      examined. This case highlights the important role of the pathologist in assessing
      donor kidneys with evidence of neoplasia.

PMID- 25055968
TI  - Transatlantic comparative health policy analyses: introduction.

PMID- 25055967
TI  - Deep sequencing extends the diversity of human papillomaviruses in human skin.
AB  - Most viruses in human skin are known to be human papillomaviruses (HPVs).
      Previous sequencing of skin samples has identified 273 different cutaneous HPV
      types, including 47 previously unknown types. In the present study, we wished to
      extend prior studies using deeper sequencing. This deeper sequencing without
      prior PCR of a pool of 142 whole genome amplified skin lesions identified 23
      known HPV types, 3 novel putative HPV types and 4 non-HPV viruses. The complete
      sequence was obtained for one of the known putative types and almost the complete
      sequence was obtained for one of the novel putative types. In addition,
      sequencing of amplimers from HPV consensus PCR of 326 skin lesions detected 385
      different HPV types, including 226 previously unknown putative types. In
      conclusion, metagenomic deep sequencing of human skin samples identified no less
      than 396 different HPV types in human skin, out of which 229 putative HPV types
      were previously unknown. 

PMID- 25055969
TI  - Structural and functional stability of cellulase in aqueous-biamphiphilic ionic
      liquid surfactant solution.
AB  - In order to explore the potential of a biamphiphilic ionic liquid surfactant as
      an enzyme stabilizer in detergents, we have investigated the structural and
      functional stability of cellulase upon interaction with 3-methyl-1
      octylimidazolium dodecylsulfate, [C8mim][C12OSO3], in aqueous medium at pH 4.8.
      Adsorption and binding isotherms determined from tensiometry and isothermal
      titration calorimetry indicated that [C8mim][C12OSO3] interacts with cellulase
      distinctly at the three critical concentrations, viz., aggregation, C1,
      saturation, C2, and vesicular, C3. Fluorescence (at lambdaex = 280 nm), far UV
      circular dichroism spectra, and dynamic light scattering results have shown that
      [C8mim][C12OSO3] alters the tertiary and secondary structure of cellulase with a
      slight initial unfolding in the monomeric regime (up to C1), refolding in the
      aggregation regime (up to C2), and unfolding in the shared aggregation regimes
      (below C3) and stabilizes the altered conformation in the post-vesicular regime
      with an overall variation of hydrodynamic diameter from 4.12 to 7.19 nm. A
      dinitrosalicylic acid sugar assay test showed excellent functional stability of
      cellulase with an activity of >=1 unit/mg in all the concentration regimes. A
      very good surface activity (J. Phys. Chem. B 2012, 116, 14363) complied by the
      present results vindicates the candidature of [C8mim][C12OSO3] as a potential
      alternative of mixed micelles or nonionic surfactants for cellulase stabilization
      in detergent industries. 

PMID- 25055970
TI  - Efficient asymmetric synthesis of 1-cyano-tetrahydroisoquinolines from lipase
      dual activity and opposite enantioselectivities in alpha-Aminonitrile resolution.
AB  - Dual promiscuous racemization/amidation activities of lipases leading to
      efficient dynamic kinetic resolution protocols of racemic alpha-aminonitrile
      compounds are described. alpha-Amidonitrile products of high enantiomeric purity
      could be formed in high yields. Several lipases from different sources were shown
      to exhibit the dual catalytic activities, where opposite enantioselectivities
      could be recorded for certain substrates. 

PMID- 25055971
TI  - A novel experimental design method to optimize hydrophilic matrix formulations
      with drug release profiles and mechanical properties.
AB  - To investigate the effects of hydrophilic polymers on the matrix system, an
      experimental design method was developed to integrate response surface
      methodology and the time series modeling. Moreover, the relationships among
      polymers on the matrix system were studied with the evaluation of physical
      properties including water uptake, mass loss, diffusion, and gelling index. A
      mixture simplex lattice design was proposed while considering eight input control
      factors: Polyethylene glycol 6000 (x1 ), polyethylene oxide (PEO) N-10 (x2 ), PEO
      301 (x3 ), PEO coagulant (x4 ), PEO 303 (x5 ), hydroxypropyl methylcellulose
      (HPMC) 100SR (x6 ), HPMC 4000SR (x7 ), and HPMC 10(5) SR (x8 ). With the
      modeling, optimal formulations were obtained depending on the four types of
      targets. The optimal formulations showed the four significant factors (x1 , x2 ,
      x3 , and x8 ) and other four input factors (x4 , x5 , x6 , and x7 ) were not
      significant based on drug release profiles. Moreover, the optimization results
      were analyzed with estimated values, targets values, absolute biases, and
      relative biases based on observed times for the drug release rates with four
      different targets. The result showed that optimal solutions and target values had
      consistent patterns with small biases. On the basis of the physical properties of
      the optimal solutions, the type and ratio of the hydrophilic polymer and the
      relationships between polymers significantly influenced the physical properties
      of the system and drug release. This experimental design method is very useful in
      formulating a matrix system with optimal drug release. Moreover, it can
      distinctly confirm the relationships between excipients and the effects on the
      system with extensive and intensive evaluations.

PMID- 25055972
TI  - Dynamics of methanol in ionic liquids: validity of the Stokes-Einstein and Stokes
      Einstein-Debye relations.
AB  - The validity of Stokes-Einstein (SE) and Stokes-Einstein-Debye (SED) relations
      for methanol in the physical environment of the ionic liquid (IL) 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide is studied by means of
      nuclear magnetic resonance (NMR) relaxation time experiments, viscosity
      measurements and molecular dynamics (MD) simulations. The reorientational
      correlation times of the hydroxyl groups of pure methanol and of methanol in the
      IL/methanol mixtures were determined. For that purpose an approach for estimating
      NMR deuteron quadrupole coupling constants, presented by Wendt and Farrar (Mol.
      Phys. 1998, 95, 1077-1081), was confirmed. The self-diffusion coefficients of
      methanol were taken from the MD simulations. The viscosities of all systems were
      then measured and the SE and SED relations validated. For pure methanol both
      relations are valid, whereas they become increasingly invalid with increasing IL
      concentration, as indicated by effective volumes and radii that are too low. The
      deviation from the SE and SED relations could be related to dynamical
      heterogeneities described by the non-Gaussian parameter alpha(t) obtained from MD
      simulations. For pure methanol, alpha(t) is close to zero in accord with the
      validity of both relations. With increasing IL concentration the dynamical
      heterogeneities of methanol increase strongly. The times t* at the maximum of
      alpha(t) increase linearly with the relative number of methanol monomers in the
      mixtures. Thus, the dynamical heterogeneities are largest for single methanol
      molecules fully embedded in the IL environment. In their own environment methanol
      molecules are highly mobile, whereas in the IL-rich region the mobility is
      strongly reduced leading to the non-validity of SE and SED relations.

PMID- 25055973
TI  - Phosphaketenes as building blocks for the synthesis of triphospha heterocycles.
AB  - Unsaturated phosphorus compounds, such as phosphaalkenes and phosphaalkynes, show
      a versatile reactivity in cycloadditions. Although phosphaketenes (R-P=C=O) have
      been known for three decades, their chemistry has remained limited. Herein, we
      show that heteroatom-substituted phosphaketenes, R(3) E-P=C=O (E=Si, Sn), are
      building blocks for silyl- and stannyl-substituted five-membered heterocycles
      containing three phosphorous atoms. The structure of the heterocyclic anion
      depends on the nature of the tetrel atom involved. Although the silyl analogue
      [P(3)C(2) (OSiR(3))(2)](-) is an aromatic 1,2,4-triphospholide, the stannyl
      compound [P(CO)(2) (PSnR(3))(2)](-) is a 1,2,4-triphosphacyclopenta-3,5-dionate
      with a delocalized OCPCO fragment. Because of their anionic character, these
      compounds can easily be used as building blocks, for example, in the preparation
      of a silyl-functionalized hexaphosphaferrocene or the parent 1,2,4
      triphosphacyclopenta-3,5-dionate [P(CO)(2) (PH)(2)](-). NMR spectroscopic
      investigations and computations have shown that the heterocycle-formation
      reactions presented herein are remarkably complex.

PMID- 25055975
TI  - Genome-wide association analysis to identify SNP markers affecting teat numbers
      in an F2 intercross population between Landrace and Korean native pigs.
AB  - Most reproductive traits have low heritability and are greatly affected by
      environmental factors. Teat number and litter size are traits related to the
      reproduction ability of pigs. To identify quantitative trait loci (QTLs) for teat
      number traits, a genome-wide association study (GWAS) was conducted using an F2
      intercross between Landrace and Korean native pigs. Genotype analysis was
      performed using the porcine SNP 60 K beadchip. The GWAS was performed using a
      mixed-effects model and linear regression approach. When a genome-wide threshold
      was determined using the Bonferroni method (P = 1.61 * 10(-6)), 38 single
      nucleotide polymorphism (SNP) markers in pig chromosome 7 (SSC7) were
      significantly associated with three teat number traits (total teat number, left
      teat number, and right teat number). Among these, SNPs in 5 genes (HDDC3,
      LOC100156276, LOC100155863, ANPEP, SCAMP2) were selected for further study based
      primarily on their statistical significance. A significant association was
      detected in SCAMP2 g.25280 G>A for total teat number (P = 2.0 * 10(-12)), HDDC3
      g.1319 G>A SNP for left teat number (P = 2.3 * 10(-7)), and SCAMP2 g.14198 G>A
      for right teat number (P = 4.7 * 10(-12)). These results provide valuable
      information about the selective breeding for desirable teat numbers in pigs. 

PMID- 25055974
TI  - Genome sequence of the model sulfate reducer Desulfovibrio gigas: a comparative
      analysis within the Desulfovibrio genus.
AB  - Desulfovibrio gigas is a model organism of sulfate-reducing bacteria of which
      energy metabolism and stress response have been extensively studied. The complete
      genomic context of this organism was however, not yet available. The sequencing
      of the D. gigas genome provides insights into the integrated network of energy
      conserving complexes and structures present in this bacterium. Comparison with
      genomes of other Desulfovibrio spp. reveals the presence of two different
      CRISPR/Cas systems in D. gigas. Phylogenetic analysis using conserved protein
      sequences (encoded by rpoB and gyrB) indicates two main groups of Desulfovibrio
      spp, being D. gigas more closely related to D. vulgaris and D. desulfuricans
      strains. Gene duplications were found such as those encoding fumarate reductase,
      formate dehydrogenase, and superoxide dismutase. Complexes not yet described
      within Desulfovibrio genus were identified: Mnh complex, a v-type ATP-synthase as
      well as genes encoding the MinCDE system that could be responsible for the larger
      size of D. gigas when compared to other members of the genus. A low number of
      hydrogenases and the absence of the codh/acs and pfl genes, both present in D.
      vulgaris strains, indicate that intermediate cycling mechanisms may contribute
      substantially less to the energy gain in D. gigas compared to other Desulfovibrio
      spp. This might be compensated by the presence of other unique genomic
      arrangements of complexes such as the Rnf and the Hdr/Flox, or by the presence of
      NAD(P)H related complexes, like the Nuo, NfnAB or Mnh. 

PMID- 25055976
TI  - Gender differences in the expression of genes involved during cardiac development
      in offspring from dams on high fat diet.
AB  - Previously we have demonstrated that maternal high fat diet (HF) during pregnancy
      increase cardiovascular risk in the offspring, and pharmacological intervention
      using statins in late pregnancy reduced these risk factors. However the effects
      of maternal HF-feeding and statin treatment during pregnancy on development of
      heart remain unknown. Hence we measured expression of genes involved in cell
      cycle progression (cyclin G1), ventricular remodelling brain natriuretic peptide
      (BNP), and environmental stress response small proline-rich protein 1A (SPRR 1A)
      in the offspring left ventricle (LV) from dams on HF with or without statin
      treatment. Female C57 mice were fed a HF diet (45% kcal fat) 4 weeks prior to
      conception, during pregnancy and lactation. From the second half of the pregnancy
      and throughout lactation, half of the pregnant females on HF diet were given a
      water-soluble statin (Pravastatin) in their drinking water (HF + S). At weaning
      offspring were fed HF diet to adulthood (generating dam/offspring dietary groups
      HF/HF and HF + S/HF). These groups were compared with offspring from dams fed
      standard chow (C 21% kcal fat) and fed C diet from weaning (C/C). LV mRNA levels
      for cyclin G1, BNP and SPRR 1A were measured by RT-PCR. Heart weights and BP in
      HF/HF offspring were higher versus C/C group. Maternal Pravastatin treatment
      reduced BP and heart weights in HF + S/HF female offspring to levels found in C/C
      group. LV cyclin G1 mRNA levels were lower in HF/HF versus both C/C and HF + S/HF
      offspring. BNP mRNA levels were elevated in HF/HF females but lower in males
      versus C/C. BNP gene expression in HF + S/HF offspring was similar to HF/HF. SPRR
      1A mRNA levels were similar in all treatment groups. Statins given to HF-fed
      pregnant dams reduced cardiovascular risk in adult offspring, and this is
      accompanied by changes in expression of genes involved in adaptive remodelling in
      the offspring LV and that there is a gender difference.

PMID- 25055977
TI  - Effect of nitrogen and temperature on the transcription of an ACAT gene in
      Isochrysis galbana.
AB  - Thiolases are functionally divided into two groups: 3-ketoacyl-CoA thiolase and
      acetoacetyl-CoA thiolase (ACAT). Acetoacetyl-CoA thiolase plays a key role in the
      mevalonate pathway. In this study, a novel gene, IgACAT, which encodes ACAT was
      cloned from Isochrysis galbana and characterized. The cDNA of IgACAT was 1551 bp
      in length, consisting of an open reading frame of 1173 bp, a 5' untranslated
      region of 69 bp and a 3' untranslated region of 309 bp. The deduced amino acid
      sequence of IgACAT was 390 amino acid residues in length with a predicted
      molecular weight of 53.59 kDa and an isoelectric point of pH 9.04. The
      triterpenes content and the expression of IgACAT under nitrogen and temperature
      stress were analyzed. When I. galbana was treated with excessive nitrogen and at
      35  degrees C, respectively, both the triterpenes content and the abundance of
      IgACAT gene transcript increased. Our findings will facilitate the regulation of
      gene expression and genetic modification of the triterpenes synthesis pathway of
      I. galbana. 

PMID- 25055978
TI  - Thioredoxin/thioredoxin reductase system involvement in cerebellar granule cell
      apoptosis.
AB  - The involvement of thioredoxin/thioredoxin reductase system has been investigated
      in cerebellar granule cells (CGCs), a cellular system in which neurons are
      induced in apoptosis by the physiological stimulus of lowering extracellular
      potassium. Clarifying the sequence of events that occur during apoptosis is a
      critical issue as it can lead to the identification of those key events that, if
      blocked, can slow down or reverse the death process. The results reported in this
      work show that TrxR is involved in the early phase of CGC apoptosis with an
      increase in activity that coincides with the increased expression of the TrxR1
      isoform and guarantees the maintenance of adequate level of Trx in its reduced,
      active form. However, in late apoptosis, when about 50 % of cells are dead,
      partial proteolysis of TrxR1 by calpain occurs and the reduction of TrxR1 mRNA,
      together with the overall decrease in TrxR activity, contribute to increase the
      levels of the oxidized form of Trx. When the reduced form of Trx is externally
      added to apoptotic cultures, a significant reduction in cell death is achieved
      confirming that a well-functioning thioredoxin/thioredoxin reductase system is
      required for survival of CGCs. 

PMID- 25055979
TI  - Self-assembled isoporous block copolymer membranes with tuned pore sizes.
AB  - The combination of nonsolvent-induced phase separation and the self-assembly of
      block copolymers can lead to asymmetric membranes with a thin highly ordered
      isoporous skin layer. The effective pore size of such membranes is usually larger
      than 15 nm. We reduced the pore size of these membranes by electroless gold
      deposition. We demonstrate that the pore sizes can be controlled precisely
      between 3 and 20 nm leading to a tunable sharp size discrimination in filtration
      processes. Besides fractionation of nanoparticles and biomaterials, controlled
      drug delivery is an attractive potential application. 

PMID- 25055981
TI  - Singly modified amikacin and tobramycin derivatives show increased rRNA A-site
      binding and higher potency against resistant bacteria.
AB  - Semisynthetic derivatives of the clinically useful aminoglycosides tobramycin and
      amikacin were prepared by selectively modifying their 6'' positions with a
      variety of hydrogen bond donors and acceptors. Their binding to the rRNA A-site
      was probed using an in vitro FRET-based assay, and their antibacterial activities
      against several resistant strains (e.g., Pseudomonas aeruginosa, Klebsiella
      pneumonia, MRSA) were quantified by determining minimum inhibitory concentrations
      (MICs). The most potent derivatives were evaluated for their eukaryotic
      cytotoxicity. Most analogues displayed higher affinity for the bacterial A-site
      than the parent compounds. Although most tobramycin analogues exhibited no
      improvement in antibacterial activity, several amikacin analogues showed potent
      and broad-spectrum antibacterial activity against resistant bacteria. Derivatives
      tested for eukaryotic cytotoxicity exhibited minimal toxicity, similar to the
      parent compounds. 

PMID- 25055982
TI  - Sleep as a predictive factor for the onset and resolution of multi-site pain: a 5
      year prospective study.
AB  - BACKGROUND: Disturbed sleep and pain often co-exist and the relationship between
      the two conditions is complex and likely reciprocal. This 5-year prospective
      study examines whether disturbed sleep can predict the onset of multi-site pain,
      and whether non-disturbed sleep can predict the resolution of multi-site pain.
      METHODS: The cohort (n = 1599) was stratified by the number of self-reported pain
      sites: no pain, pain from 1-2 sites and multi-site pain (>=3 pain sites). Sleep
      was categorized by self-reported sleep disturbance: sleep A (best sleep), sleep B
      and sleep C (worst sleep). In the no-pain and pain-from-1-2 sites strata, the
      association between sleep (A, B and C) and multi-site pain 5 years later was
      analysed. Further, the prognostic value of sleep for the resolution of multi-site
      pain at follow-up was calculated for the stratum with multi-site pain at
      baseline. In the analyses, gender, age, body mass index, smoking, physical
      activity and work-related exposures were treated as potential confounders.
      RESULTS: For individuals with no pain at baseline, a significantly higher odds
      ratio for multi-site pain 5 years later was seen for the tertile reporting worst
      sleep [odds ratio (OR) 4.55; 95% confidence interval (CI) 1.28-16.12]. Non
      disturbed (or less disturbed) sleep had a significant effect when predicting the
      resolution of multi-site pain (to no pain) (OR 3.96; 95% CI 1.69-9.31).
      CONCLUSION: In conclusion, sleep could be relevant for predicting both the onset
      and the resolution of multi-site pain. It seems to be a significant factor to
      include in research on multi-site pain and when conducting or evaluating
      intervention programmes for pain.

PMID- 25055983
TI  - Consensus recommendations for using the Multiplate((r)) for platelet function
      monitoring before cardiac surgery.
AB  - Patients requiring urgent cardiac surgery are usually already taking antiplatelet
      drugs including aspirin and a P2Y12 ADP receptor antagonist (e.g., clopidogrel,
      prasugrel or ticagrelor). This presents clinicians with the challenge of
      balancing the risk of thrombotic complications, if antiplatelet drugs are stopped
      before surgery, with the problems of excessive bleeding when surgery is performed
      in the absence of adequate platelet function. Preoperative platelet function
      monitoring is able to identify when patients have recovered platelet function.
      The Multiplate((r)) (multiple electrode impedance platelet aggregometer) is a
      point of care device that enables monitoring of platelet function. The authors
      offer recommendations based on real-world, collective experience in the use of
      platelet function monitoring. These cover the use of the Multiplate((r)) analyser
      to predict the need for platelet transfusion in the perioperative period and the
      individualized waiting period after cessation of P2Y12 ADP receptor antagonists
      before cardiac surgery. 

PMID- 25055980
TI  - The effects of aging on insight into illness in schizophrenia: a review.
AB  - OBJECTIVES: Impaired insight into illness is a prevalent feature of
      schizophrenia, which negatively influences treatment adherence and clinical
      outcomes. Little is known about the effects of aging on insight impairment. We
      aimed to review the available research literature on the effects of aging on
      insight into illness in schizophrenia, in relation to positive, negative, and
      cognitive symptoms. Ultimately, we propose a trajectory of insight in
      schizophrenia across the lifespan. METHOD: A systematic Medline(r) literature
      search was conducted, searching for English language studies describing the
      relationship of insight into illness in schizophrenia with aging. RESULTS: We
      identified 62 studies. Insight impairment is associated with illness severity,
      premorbid intellectual function (i.e. IQ), executive function, and memory.
      Insight impairment improves modestly during midlife, worsening again in late
      life. It tends to fluctuate with each episode of psychosis, likely in relation to
      worsening positive symptoms that improve with antipsychotic treatment. The
      relationship between insight impairment and cognitive dysfunction appears to
      attenuate with age, while the relationship with lower premorbid intellectual
      function is preserved. The association between impaired insight and negative
      symptoms is unclear. CONCLUSIONS: The available literature suggests that the
      course of insight impairment follows a U-shaped curve, where insight impairment
      is severe during the first episode of psychosis, modestly improves over midlife,
      and declines again in late life. Future studies are required to investigate the
      trajectory of insight into illness and its core domains across the lifespan from
      prodromal phase to late life.

PMID- 25055984
TI  - Knowledge-fused differential dependency network models for detecting significant
      rewiring in biological networks.
AB  - BACKGROUND: Modeling biological networks serves as both a major goal and an
      effective tool of systems biology in studying mechanisms that orchestrate the
      activities of gene products in cells. Biological networks are context-specific
      and dynamic in nature. To systematically characterize the selectively activated
      regulatory components and mechanisms, modeling tools must be able to effectively
      distinguish significant rewiring from random background fluctuations. While
      differential networks cannot be constructed by existing knowledge alone, novel
      incorporation of prior knowledge into data-driven approaches can improve the
      robustness and biological relevance of network inference. However, the major
      unresolved roadblocks include: big solution space but a small sample size; highly
      complex networks; imperfect prior knowledge; missing significance assessment; and
      heuristic structural parameter learning. RESULTS: To address these challenges, we
      formulated the inference of differential dependency networks that incorporate
      both conditional data and prior knowledge as a convex optimization problem, and
      developed an efficient learning algorithm to jointly infer the conserved
      biological network and the significant rewiring across different conditions. We
      used a novel sampling scheme to estimate the expected error rate due to "random"
      knowledge. Based on that scheme, we developed a strategy that fully exploits the
      benefit of this data-knowledge integrated approach. We demonstrated and validated
      the principle and performance of our method using synthetic datasets. We then
      applied our method to yeast cell line and breast cancer microarray data and
      obtained biologically plausible results. The open-source R software package and
      the experimental data are freely available at
      http://www.cbil.ece.vt.edu/software.htm. CONCLUSIONS: Experiments on both
      synthetic and real data demonstrate the effectiveness of the knowledge-fused
      differential dependency network in revealing the statistically significant
      rewiring in biological networks. The method efficiently leverages data-driven
      evidence and existing biological knowledge while remaining robust to the false
      positive edges in the prior knowledge. The identified network rewiring events are
      supported by previous studies in the literature and also provide new mechanistic
      insight into the biological systems. We expect the knowledge-fused differential
      dependency network analysis, together with the open-source R package, to be an
      important and useful bioinformatics tool in biological network analyses.

PMID- 25055985
TI  - Epidermal gene expression and ethnic pigmentation variations among individuals of
      Asian, European and African ancestry.
AB  - Differences in visible skin pigmentation give rise to the wide variation of skin
      colours seen in racial/ethnic populations. Skin pigmentation is important not
      only from cosmetic and psychological points of view, but more importantly because
      of its implications for the risk of all types of skin cancers, on photoaging,
      etc. Despite differences in those parameters in Caucasian and Asian skin types,
      they are remarkably similar in their production and distribution of melanins, and
      the mechanism(s) underlying their different characteristics have remained
      obscure. In this study, we used microarray analysis of skin suction blisters to
      investigate molecular differences underlying the determination of pigmentation in
      various skin types, and we used immunohistochemistry to validate the expression
      patterns of several interesting targets that were identified. Intriguingly,
      Caucasian and Asian skins had highly similar gene expression patterns that
      differed significantly from the pattern of African skin. The results of this
      study suggest the dynamic interactions of different types of cells in human skin
      that regulate its pigmentation, reveal that the known pigmentation genes have a
      limited contribution and uncover a new array of genes, including NINL and S100A4,
      that might be involved in that regulation. 

PMID- 25055986
TI  - Metabolome variations in the Porphyromonas gingivalis vimA mutant during hydrogen
      peroxide-induced oxidative stress.
AB  - The adaptability and survival of Porphyromonas gingivalis in the oxidative
      microenvironment of the periodontal pocket are indispensable for survival and
      virulence, and are modulated by multiple systems. Among the various genes
      involved in P. gingivalis oxidative stress resistance, vimA gene is a part of the
      6.15-kb locus. To elucidate the role of a P. gingivalis vimA-defective mutant in
      oxidative stress resistance, we used a global approach to assess the
      transcriptional profile, to study the unique metabolome variations affecting
      survival and virulence in an environment typical of the periodontal pocket. A
      multilayered protection strategy against oxidative stress was noted in P.
      gingivalis FLL92 with upregulation of detoxifying genes. The duration of
      oxidative stress was shown to differentially modulate transcription with 94 (87%)
      genes upregulated twofold during 10 min and 55 (83.3%) in 15 min. Most of the
      upregulated genes (55%), fell in the hypothetical/unknown/unassigned functional
      class. Metabolome variation showed reduction in fumarate and formaldehyde, hence
      resorting to alternative energy generation and maintenance of a reduced metabolic
      state. There was upregulation of transposases, genes encoding for the metal ion
      binding protein transport and secretion system.

PMID- 25055987
TI  - Early economic evaluation of emerging health technologies: protocol of a
      systematic review.
AB  - BACKGROUND: The concept of early health technology assessment, discussed well
      over a decade, has now been collaboratively implemented by industry, government,
      and academia to select and expedite the development of emerging technologies that
      may address the needs of patients and health systems. Early economic evaluation
      is essential to assess the value of emerging technologies, but empirical data to
      inform the current practice of early evaluation is limited. We propose a
      systematic review of early economic evaluation studies in order to better
      understand the current practice. METHODS/DESIGN: This protocol describes a
      systematic review of economic evaluation studies of regulated health technologies
      in which the evaluation is conducted prior to regulatory approval and when the
      technology effectiveness is not well established. Included studies must report an
      economic evaluation, defined as the comparative analysis of alternatives with
      respect to their associated costs and health consequences, and must evaluate some
      regulated health technology such as pharmaceuticals, biologics, high-risk medical
      devices, or biomarkers. We will conduct the literature search on multiple
      databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination
      Databases, and EconLit. Additional citations will be identified via scanning
      reference lists and author searching. We suspect that many early economic
      evaluation studies are unpublished, especially those conducted for internal use
      only. Additionally, we use a chain-referral sampling approach to identify authors
      of unpublished studies who work in technology discovery and development, starting
      out with our contact lists and authors who published relevant studies. Citation
      screening and full-text review will be conducted by pairs of reviewers.
      Abstracted data will include those related to the decision context and decision
      problem of the early evaluation, evaluation methods (e.g., data sources, methods,
      and assumptions used to identify, measure, and value the likely effectiveness and
      the costs and consequences of the new technology, handling of uncertainty), and
      whether the study results adequately address the main study question or
      objective. Data will be summarized overall and stratified by publication status.
      DISCUSSION: This study is timely to inform early economic evaluation practice,
      given the international trend in early health technology assessment initiatives.

PMID- 25055989
TI  - Cessation of antithrombotic therapy before surgery: weighing thrombosis and
      bleeding risks.

PMID- 25055988
TI  - Female sex as a risk factor for thromboembolism and death in patients with
      incident atrial fibrillation. The prospective Danish Diet, Cancer and Health
      study.
AB  - Several studies have demonstrated sex differences in risk of thromboembolism and
      death among patients with atrial fibrillation, but it is unclear to what extent
      these associations relate to actual physiological differences. To date, no study
      has investigated sex differences with concomitant control for lifestyle related
      factors known to influence stroke risk. We used data from the Danish Diet, Cancer
      and Health study, including 57,053 participants (52% female) aged 50-64 years.
      The study population for this study included the 2,895 patients (36% female) with
      incident atrial fibrillation after inclusion. Data were linked to outcomes
      identified using nationwide registries. Risk of thromboembolism and death
      according to female sex were analysed using Cox proportional hazards models.
      After a median follow-up of 5.0 years, 137 men and 62 women suffered a
      thromboembolic event, and 349 men and 151 women died. In a crude analysis, female
      sex was associated with a non-significant lower risk of thromboembolism (hazard
      ratio [HR] 0.82, 95% confidence interval [CI] 0.61-1.11). Adjustment for
      differences in antithrombotic therapy, relevant comorbidities and lifestyle did
      not change this association (HR 0.77, 95% CI 0.55-1.13). In the final model,
      female sex was associated with a lower risk of death (HR 0.65, 95% CI 0.51-0.84).
      The associations were similar in a sensitivity analysis of women not taking
      hormone replacement therapy, and the effect of hormone replacement therapy use
      within females was non-significant for both endpoints of thromboembolism and
      death. In conclusion, in a relatively young population of patients with atrial
      fibrillation, female sex was associated with a lower risk of thromboembolism and
      death. 

PMID- 25055990
TI  - Preoperative statin therapy and infectious complications in cardiac surgery.
AB  - AIM: To assess whether preoperative statin therapy is associated with the risk of
      postoperative infection in patients undergoing cardiac surgery. METHODS: 520
      patients undergoing cardiac surgery in 2010 were retrospectively examined. Data
      regarding statin and antibiotic use prior to and after surgery were available
      from the hospital pharmacy information system. Cultures and clinical data of
      patients on postoperative antibiotics other than standard prophylactic therapy
      were studied to identify postoperative infections up to 30 days from day of
      surgery. RESULTS: 370 (71.2 %) patients were on preoperative statin therapy.
      Overall, 82 patients (15.8 %) suffered from postoperative infection of which 11
      were surgical site infections. In multivariable regression analysis, statin
      therapy was associated with a reduced risk of postoperative infection (adjusted
      odds ratio: 0.329, 95 %: CI 0.19-0.57; P < 0.001). CONCLUSIONS: Preoperative
      statin use was associated with a considerable reduced risk of postoperative
      infections following cardiac surgery. Randomised controlled trials are required
      to clarify the role of statin therapy in the prevention of postoperative
      infections.

PMID- 25055991
TI  - Proximal tubule morphology in rats with renal congestion: a study involving the
      in vivo cryotechnique.
AB  - The present study aimed to examine the changes induced in proximal tubules by
      renal congestion using the in vivo cryotechnique (IVCT). Twelve male Wistar rats
      were divided into four equal groups: group 1 (the control); groups 2 and 3, which
      were subjected to 2 and 5 min of congestion, respectively; and group 4, which was
      subjected to 5 min of congestion followed by 10 min of recirculation. Under
      anesthesia, renal congestion was induced in the bilateral kidneys by ligating the
      inferior vena cava just above the branching renal veins. The left kidneys, which
      were subjected to the IVCT, were then compared with the right kidneys, which
      underwent a conventional fixation method. Among the left kidneys, the proximal
      tubules in group 1 consisted of cuboidal cells and had open lumina. In the
      congestive groups, the diameters of the proximal tubules were increased, and
      their lumina were obstructed by swollen cells and ischemia-associated cell
      debris. In group 4, the proximal tubules were still dilated, as seen in the
      congestive groups; however, the swollen cells had recovered their cuboidal form,
      and the cell debris had disappeared from the tubules' lumina. The present study
      demonstrated the in vivo morphology of proximal tubules in living rats subjected
      to congestion, which was unclear using conventional fixation methods. 

PMID- 25055992
TI  - Ultrastructural immunolocalization of laminin 332 (laminin 5) at dento-gingival
      interface in Macaca fuscata monkey.
AB  - Although laminin 332 (laminin 5), an extracellular matrix molecule involved in
      cell adhesion and migration, has been localized at the interface between the
      tooth enamel and junctional epithelium, its ultrastructural localization remains
      to be fully clarified. The purpose of the present study was to investigate the
      ultrastructural distribution of laminin 332 at the dento-gingival interface in
      Japanese monkey (Macaca fuscata) using pre- and post-embedding immunoelectron
      microscopy. Pre-embedding immunoelectron microscopy revealed a broad band of
      internal basal lamina together with supplementary lamina densa, and both showed
      immunolabeling for laminin 332. Immunoreaction products for laminin 332 were
      observed in the rough-surfaced endoplasmic reticulum of the junctional epithelial
      cells close to the tooth enamel. Post-embedding immunoelectron microscopy
      revealed an increase in the number of immunogold particles toward the coronal
      portion, resulting in a large accumulation of particles on the basal lamina,
      preferentially on the lamina densa. Concomitantly the dental cuticle at the dento
      gingival interface was sporadically, but specifically, immunogold-labeled with
      anti-laminin 332 antibody. These data suggest that junctional epithelium actively
      produces laminin 332, and that the products accumulate at the dento-gingival
      interface during cell migration coronally towards the gingival sulcus. 

PMID- 25055993
TI  - Sex-dependent activity of de novo methyltransferase 3 (Tudnmt3) in the two
      spotted mite, Tetranychus urticae Koch.
AB  - DNA methylation is an epigenetic mechanism for regulating developmental and other
      important processes in eukaryotes. Several components of the DNA methylation
      machinery have been identified, such as DNA methyltransferases. However, little
      is known about DNA methyltransferases in chelicerates, which is the second
      largest arthropod group. Epigenetics are expected to have a crucial role in the
      metabolism and development of this group. Here, we investigated the role of DNA
      methyltransferase 3 in the development of Tetranychus urticae Koch. In silico
      analyses clearly showed that this enzyme possesses the necessary conserved motifs
      for the catalytic activity of de novo methylation of DNA. Real-time PCR revealed
      that T. urticae de novo methyltransferase 3 (Tudnmt3) is expressed ubiquitously
      and throughout the life cycle of the two-spotted spider mite. However, the
      pattern of Tudnmt3 expression was sex-dependent during the adult stage. Whole in
      situ hybridization provided supportive evidence that Tudnmt3 is linked to the
      differentiation of the gonads in adult females and males. Methylation-sensitive
      amplification polymorphism analyses of 119 loci showed that the status of DNA
      methylation is partially different between adult females and males, raising the
      possibility that this sex-dependent DNA methylation pattern is mediated by
      different methylation activity of Tudnmt3. 

PMID- 25055994
TI  - Design of the standardizing care to improve outcomes in pediatric end stage renal
      disease collaborative.
AB  - The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease
      (SCOPE) Collaborative is a North American multi-center quality transformation
      effort whose primary aim is to minimize exit-site infection and peritonitis rates
      among pediatric chronic peritoneal dialysis patients. The project, developed by
      the quality improvement faculty and staff at the Children's Hospital
      Association's Quality Transformation Network (QTN) and content experts in
      pediatric nephrology and pediatric infectious diseases, is modeled after the
      QTN's highly successful Pediatric Intensive Care Unit and Hematology-Oncology
      central line-associated blood-stream infection (CLABSI) Collaboratives. Like the
      Association's other QTN efforts, the SCOPE Collaborative is part of a broader
      effort to assist pediatric nephrology teams in learning about and using quality
      improvement methods to develop and implement evidence-based practices. In
      addition, the design of this project allows for targeted research that builds on
      high-quality, ongoing data collection. Finally, the project, while focused on
      reducing peritoneal dialysis catheter-associated infections, will also serve as a
      model for future pediatric nephrology projects that could further improve the
      quality of care provided to children with end stage renal disease. 

PMID- 25055995
TI  - The in vitro effects of sodium salicylate on von Willebrand factor and C-reactive
      protein production by endothelial cells.
AB  - OBJECTIVE: The role of inflammatory and endothelial dysfunction markers in the
      atherogenic process has been well recognized. The data have made both C-reactive
      protein (CRP) and von Willebrand factor (vWF) promising targets for the
      cardiovascular disease research and drug development. Inhibition of CRP and vWF
      synthesis, therefore, might be a potential therapeutic strategy. METHODS: The
      effect of sodium salicylate on vWF production by human umbilical vein endothelial
      cells (HUVECs) using enzyme-linked immunosorbent Assays (ELISA) and real-time PCR
      was examined. In addition, small interfering RNA (siRNA) against NF-kappaB was
      used to investigate the existence of a role for this signaling pathway. RESULTS:
      Our findings demonstrated that sodium salicylate decreased vWF, but not CRP
      production at both mRNA and protein levels significantly and this might not occur
      via nuclear transcription factor (NF-kappaB) inhibition. CONCLUSION: Our results
      indicated a further rationalization of the effects of sodium salicylate on
      atherothrombotic events by attenuation of vWF production.

PMID- 25055996
TI  - Aqueous extract of post-fermented tea reverts the hepatic steatosis of
      hyperlipidemia rat by regulating the lipogenic genes expression and hepatic fatty
      acid composition.
AB  - BACKGROUND: Post-fermented tea has been used for the prevention of metabolic
      syndrome in Western China. Present study reports the biochemical mechanism of
      lipid-lowering effects of Jing-wei fu tea (JWFT), a variety of post-fermented tea
      on high-fat diet-induced hyperglycemia and obesity in rats. METHODS: Aqueous
      extract of JWFT was prepared by putting them in boiling water, and then
      concentrated under reduced pressure. The major compounds of JWFT were determined
      by high performance liquid chromatography (HPLC). High-fat diet fed rats were
      orally administered different doses of JWFT aqueous extract (0.5, 1.0 and 2.0
      g/kg) for four weeks. At the end of this experiment, hepatic lipids, serum leptin
      and lipids levels were determined using enzyme-linked immunosorbent assay
      (ELISA). The hepatic fatty acid composition was analyzed using gas chromatography
      mass (GC-MS). The relative expression of lipids metabolism genes was analyzed
      using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The
      results showed that JWFT inhibited the increase in the body weight, abdominal
      adipose weight, serum lipids and hepatic lipids, and decreased serum leptin
      levels of high-fat diet fed rats. JWFT normalized hepatic fatty acid composition
      of hyperlipidemia rats by up-regulating hepatic acetyl-CoA carboxylase (ACC),
      stearoyl-CoA desaturase 1 (SCD1) and fatty acid synthase (FAS) gene expression,
      and down-regulating carnitine palmitoyl transferase-1 (CPT1). Furthermore, the
      results showed that JWFT inhibited the absorption of lipids. CONCLUSION: JWFT
      could mitigate the obesity-induced hepatic steatosis by regulating hepatic
      lipogenesis and lipolysis.

PMID- 25055997
TI  - Evaluation of a primary care-based post-discharge phone call program: keeping the
      primary care practice at the center of post-hospitalization care transition.
AB  - BACKGROUND: The post-hospitalization period is a precarious time for patients.
      Post-discharge nurse telephone call programs aiming to prevent unnecessary
      readmissions have had mixed results. OBJECTIVE: Describe a primary-care based
      program to identify and address problems arising after hospital discharge.
      DESIGN: A quality improvement program embedding registered nurses in a primary
      care practice to call patients within 72 h of hospital discharge and route
      problems within the practice for real-time resolution. PARTICIPANTS: Adult
      patients with a primary care provider in the general internal medicine practice
      at the University of California San Francisco who were discharged home from the
      Medicine service. MAIN MEASURES: Patients reached directly by phone had a 'full
      scripted encounter;' those reached only by voice-mail had a 'message-scripted
      encounter;' those not reached despite multiple attempts had a 'missed encounter.'
      Among patients with full-scripted encounters, we identified and cataloged
      problems arising after hospital discharge and measured the proportion of calls in
      which a problem was uncovered. For the different encounter types, we compared
      follow-up appointment attendance and 30-day readmission rates. KEY RESULTS: Of
      790 eligible discharges, 486 had a full-scripted, 229 a message-scripted and 75 a
      missed encounter. Among the 486 full-scripted encounters, nurses uncovered at
      least one problem in 371 (76 %) discharges, 25 % of which (n = 94) included new
      symptoms, and 47 % (n = 173) included medication issues. Discharges with full
      scripted and message-scripted encounters were associated with higher follow-up
      appointment attendance rates compared with those with missed encounters (60.1 %,
      58.5 %, 38.5 % respectively p = 0.004). There was no significant difference in 30
      day readmission rates (12.8 %, 14.8 %, 14.7 %; p = 0.72). CONCLUSIONS: Our
      results suggest that centering a post-discharge phone call program within the
      primary care practice improves post-hospital care by identifying clinical and
      care-coordination problems early. With the new Medicare transitional care
      payment, such programs could become an important, self-sustaining part of the
      patient-centered medical home.

PMID- 25055998
TI  - Role of licochalcone A on thymic stromal lymphopoietin expression: implications
      for asthma.
AB  - Asthma is a common chronic inflammatory disease characterized by the infiltration
      and accumulation of memory-like Th2 cells and eosinophils. Viral infection has
      emerged as the most common cause of severe episodes of asthma. For the treatment
      of bronchial asthma, the root of liquorice (Glycyrrhiza glabra) has been used as
      a traditional medicine in the East and West. Licochalcone A is the predominant,
      characteristic chalcone in liquorice root. To determine whether licochalcone A
      possesses an anti-inflammatory effect, we tested its effect on the expression and
      production of thymic stromal lymphopoietin (TSLP) in BEAS 2B cells and primary
      bronchial epithelial cells. We found that polyinosinic-polycytidylic acid (poly
      IC)-induced TSLP expression was suppressed by treatment with licochalcone A in a
      dose- and time-dependent manner. We also found that poly-IC-induced mRNA
      expression of other proinflammatory mediators such as MCP-1, RANTES, and IL-8 was
      suppressed by licochalcone A. Furthermore, licochalcone A suppressed poly-IC
      induced nuclear factor kappa B (NF-kappaB) nuclear translocation and DNA-binding
      activity by suppressing the Ikappabeta kinase (IKK) activity but not by direct
      phosphorylation of p65 at serine 276. Collectively, our findings suggest that
      licochalcone A suppresses poly-IC-induced TSLP expression and production by
      inhibiting the IKK/NF-kappaB signaling pathway, which might be involved in the
      pathogenesis of virus-exacerbated asthma. Further elucidation of the mechanisms
      underlying these observations can help develop therapeutic strategies for virally
      induced asthma. 

PMID- 25055999
TI  - Costs of production loss and primary health care interventions for return-to-work
      of sick-listed workers in Sweden.
AB  - PURPOSE: The aim of this study was to investigate, from the perspective of
      society, the costs of sick leave and rehabilitation of recently sick-listed
      workers with musculoskeletal disorders (MSD) or mental disorders (MD). METHODS:
      In a prospective cohort study, 812 sick-listed workers with MSD (518) or MD (294)
      were included. Data on consumption of health care and production loss were
      collected over six months from an administrative casebook system of the health
      care provider. Production loss was estimated based on the number of sick-leave
      days. Societal costs were based on the human capital approach. RESULTS: The mean
      costs of production loss per person were EUR 5978 (MSD) and EUR 6381 (MD). Health
      care interventions accounted for 9.3% (MSD) and 8.2% (MD) of the costs of
      production loss. Corresponding figures for rehabilitation activities were 3.7%
      (MSD) and 3.1% (MD). Health care interventions were received by about 95% in both
      diagnostic groups. For nearly half of the cohort, no rehabilitation intervention
      at all was provided. CONCLUSIONS: Costs associated with sick leave were dominated
      by production loss. Resources invested in rehabilitation were small. By
      increasing investment in early rehabilitation, costs to society and the
      individual might be reduced. IMPLICATIONS FOR REHABILITATION: Resources invested
      in rehabilitation for sick-listed with musculoskeletal and mental disorders in
      Sweden are very small in comparison with the costs of production loss. For policy
      makers, there may be much to gain through investments into improved
      rehabilitation processes for return to work. Health care professionals need to
      develop rehabilitative activities aiming for return to work, rather than symptoms
      treatment only.

PMID- 25056000
TI  - Discriminatory laws threaten effective response to HIV/AIDS, conference hears.

PMID- 25056001
TI  - Incidence and remission of urinary incontinence at midlife: a cohort study.
AB  - OBJECTIVE: Urinary incontinence (UI) is often considered to be an age-related
      disease that develops gradually as women grow older. Much remains to be learnt
      about factors that promote its incidence or its remission. Our objective was to
      assess its incidence and risk factors. DESIGN: Longitudinal cohort study.
      SETTING: French GAZEL cohort. POPULATION: A cohort of 4127 middle-aged women
      (aged 47-52 years at baseline) over an 18-year period (1990-2008). METHODS: UI
      was defined as 'difficulty retaining urine'. The question was asked at baseline
      and repeated every 3 years over an 18-year period. Two groups (UI incidence and
      remission) were analysed according to status at baseline (continent or
      incontinent). A multivariable analysis (Cox model) was used to estimate the risk
      factors for UI incidence and remission. MAIN OUTCOME MEASURES: Annual incidence
      and remission rates and risk factors for UI incidence and remission. RESULTS: The
      annual incidence and remission rates for UI were 3.3% and 6.2%, respectively.
      High educational level (hazard ratio [HR] = 1.28; 95% confidence interval [95%
      CI] = 1.05-1.55), parity, i.e. at least one baby versus no baby (HR = 1.64; 95%
      CI = 1.19-2.27), menopause (HR = 5.44; 95% CI = 4.47-6.63), weight gain, i.e. for
      each kilogram change in weight (HR = 1.00; 95% CI = 1.00-1.02), onset of
      depressive symptoms (HR = 1.31; 95% CI = 1.09-1.57) and impairment in health
      related quality of life incidence (social isolation dimension [HR = 1.29; 95% CI
      = 1.04-1.60] and energy dimension [HR = 1.41; 95% CI = 1.17-1.70]) were
      associated with an increased probability of UI. The factors associated with
      persistent UI were age (HR = 0.58; 95% CI = 0.55-0.61), weight gain (HR = 0.99;
      95% CI = 0.98-0.99) and transition to menopausal status (HR = 1.54; 95% CI = 1.19
      1.99). CONCLUSIONS: Our study suggests that, in our population of middle-aged
      women, age, menopause, weight gain, onset of depression and impaired health
      related quality of life may promote UI.

PMID- 25056002
TI  - Exploitation of yield stability in barley.
AB  - KEY MESSAGE: Analyses of registration trials of winter barley suggested that
      yield and yield stability can be enhanced by developing hybrid instead of line
      varieties. Yield stability is central to cope with the expected increased
      frequency of extreme weather conditions. The objectives of our study were to (1)
      examine the dimensioning of field trials needed to precisely portray yield
      stability of individual winter barley (Hordeum vulgare L.) genotypes, (2) compare
      grain yield performance and yield stability of two-rowed lines with those of six
      rowed lines and hybrids, and (3) investigate the association of various agronomic
      traits with yield stability. Static and dynamic yield stability as well as grain
      yield performance was determined in five series of 3-year registration trials of
      winter barley in Germany. Each series included 4 or 5 six-rowed hybrids, 40-46
      six-rowed inbred lines, as well as 42-49 two-rowed inbred lines. The genotypes
      were evaluated in 10-45 environments, i.e. year-by-location combinations. We
      found that precise assessment of yield stability of individual genotypes requires
      phenotyping in at least 40 test environments. Therefore, selection for yield
      stability is not usually feasible since the required number of test environments
      exceeds the common capacity of barley breeding programs. Also, indirect
      improvement of yield stability by means of agronomic traits seemed not possible
      since there was no constant association of any agronomic trait with yield
      stability. We found that compared with line varieties, hybrids showed on average
      higher grain yield performance combined with high dynamic yield stability. In
      conclusion, breeding hybrid instead of line varieties may be a promising way to
      develop high yielding and yield stable varieties.

PMID- 25056003
TI  - Comparative analysis of the radish genome based on a conserved ortholog set (COS)
      of Brassica.
AB  - KEY MESSAGE: This manuscript provides a Brassica conserved ortholog set (COS)
      that can be used as diagnostic cross-species markers as well as tools for genetic
      mapping and genome comparison of the Brassicaceae. A conserved ortholog set (COS)
      is a collection of genes that are conserved in both sequence and copy number
      between closely related genomes. COS is a useful resource for developing gene
      based markers and is suitable for comparative genome mapping. We developed a COS
      for Brassica based on proteome comparisons of Arabidopsis thaliana, B. rapa, and
      B. oleracea to establish a basis for comparative genome analysis of crop species
      in the Brassicaceae. A total of 1,194 conserved orthologous single-copy genes
      were identified from the genomes based on whole-genome BLASTP analysis. Gene
      ontology analysis showed that most of them encoded proteins with unknown function
      and chloroplast-related genes were enriched. In addition, 152 Brassica COS primer
      sets were applied to 16 crop and wild species of the Brassicaceae and 57.9-92.8 %
      of them were successfully amplified across the species representing that a
      Brassica COS can be used as diagnostic cross-species markers of diverse Brassica
      species. We constructed a genetic map of Raphanus sativus by analyzing the
      segregation of 322 COS genes in an F2 population (93 individuals) of Korean
      cultivars (WK10039 * WK10024). Comparative genome analysis based on the COS genes
      showed conserved genome structures between R. sativus and B. rapa with lineage
      specific rearrangement and fractionation of triplicated subgenome blocks
      indicating close evolutionary relationship and differentiation of the genomes.
      The Brassica COS developed in this study will play an important role in genetic,
      genomic, and breeding studies of crop Brassicaceae species.

PMID- 25056004
TI  - The effect of exercise-induced arousal on chosen tempi for familiar melodies.
AB  - Many previous studies have shown that arousal affects time perception, suggesting
      a direct influence of arousal on the speed of the pacemaker of the internal
      clock. However, it is unknown whether arousal influences the mental
      representation of tempo (speed) for highly familiar and complex stimuli, such as
      well-known melodies, that have long-term representations in memory. Previous
      research suggests that mental representations of the tempo of familiar melodies
      are stable over time; the aim of the present study was to investigate whether
      these representations can be systematically altered via an increase in
      physiological arousal. Participants adjusted the tempo of 14 familiar melodies in
      real time until they found a tempo that matched their internal representation of
      the appropriate tempo for that piece. The task was carried out before and after a
      physiologically arousing (exercise) or nonarousing (anagrams) manipulation.
      Participants completed this task both while hearing the melodies aloud and while
      imagining them. Chosen tempi increased significantly following exercise-induced
      arousal, regardless of whether a melody was heard aloud or imagined. These
      findings suggest that a change in internal clock speed affects temporal judgments
      even for highly familiar and complex stimuli such as music.

PMID- 25056005
TI  - Banana or fruit? Detection and recognition across categorical levels in RSVP.
AB  - Pictured objects and scenes can be understood in a brief glimpse, but there is a
      debate about whether they are first encoded at the basic level (e.g., banana), as
      proposed by Rosch et al. (1976, Cognitive Psychology) , or at a superordinate
      level (e.g., fruit). The level at which we first categorize an object matters in
      everyday situations because it determines whether we approach, avoid, or ignore
      the object. In the present study, we limited stimulus duration in order to
      explore the earliest level of object understanding. Target objects were presented
      among five other pictures using RSVP at 80, 53, 27, or 13 ms/picture. On each
      trial, participants viewed or heard 1 of 28 superordinate names or a
      corresponding basic-level name of the target. The name appeared before or after
      the picture sequence. Detection (as d') improved as duration increased but was
      significantly above chance in all conditions and for all durations. When the name
      was given before the sequence, d' was higher for the basic than for the
      superordinate name, showing that specific advance information facilitated visual
      encoding. In the name-after group, performance on the two category levels did not
      differ significantly; this suggests that encoding had occurred at the basic level
      during presentation, allowing the superordinate category to be inferred. We
      interpret the results as being consistent with the claim that the basic level is
      usually the entry level for object perception.

PMID- 25056006
TI  - Saccade target selection in Chinese reading.
AB  - In Chinese reading, there are no spaces to mark the word boundaries, so Chinese
      readers cannot target their saccades to the center of a word. In this study, we
      investigated how Chinese readers decide where to move their eyes during reading.
      To do so, we introduced a variant of the boundary paradigm in which only the
      target stimulus remained on the screen, displayed at the saccade landing site,
      after the participant's eyes crossed an invisible boundary. We found that when
      the saccade target was a word, reaction times in a lexical decision task were
      shorter when the saccade landing position was closer to the end of that word.
      These results are consistent with the predictions of a processing-based strategy
      to determine where to move the eyes. Specifically, this hypothesis assumes that
      Chinese readers estimate how much information is processed in parafoveal vision
      and saccade to a location that will carry novel information. 

PMID- 25056007
TI  - Is Hashimoto's thyroiditis a risk factor for medullary thyroid carcinoma? Our
      experience and a literature review.
AB  - The etiology of medullary thyroid carcinoma remains unknown. The aim of this
      study was to determine whether there is a significant association between
      medullary thyroid carcinoma and Hashimoto's thyroiditis in the histopathologic
      material of thyroidectomized patients. Retrospective cross-sectional study. In
      this study, we reviewed the medical records of all patients who underwent total
      thyroidectomy for different thyroid-related complaints between January 2000 and
      January 2012 at Jordan University Hospital-Amman, Jordan. To highlight relevant
      previously published studies addressing this topic, a literature search was
      conducted for English language studies reporting "medullary thyroid carcinoma" or
      "C-cell hyperplasia" in patients with Hashimoto's thyroiditis. Of the 863
      patients with a mean age of 47.2 +/- 12.3 years who underwent total thyroidectomy
      during the study period, 78 (9.04 %) were diagnosed with Hashimoto's thyroiditis,
      and 15 (1.74 %) had medullary thyroid carcinoma, 3 (20 %) of whom had coexistent
      Hashimoto's thyroiditis. A total of 683 (79.1 %) patients had benign thyroid
      disease, 67 (9.8 %) of whom had Hashimoto's thyroiditis. The difference between
      these rates was not statistically significant (p = 0.19). When examined by
      gender, 9 females had medullary thyroid carcinoma, 3 (33.3 %) of whom had
      coexistent Hashimoto's thyroiditis; by contrast, of 560 females with benign
      thyroid disease, 62 (11.1 %) had Hashimoto's thyroiditis (p = 0.04). Although
      this study population represents a small and single-institution experience, our
      results suggest that there might be an association between Hashimoto's
      thyroiditis and medullary thyroid carcinoma only in female patients who undergo
      total thyroidectomy.

PMID- 25056008
TI  - Genetic Testing and Neuroimaging for Youth at Risk for Mental Illness: Trading
      off Benefit and Risk.
AB  - BACKGROUND: According to the World Health Organization, mental illness is one of
      the leading causes of disability worldwide. The first onset of mental illness
      usually occurs during childhood or adolescence, with nearly 12 million diagnosed
      cases in the United States alone. Neuroimaging and genetic testing have been
      invaluable in research on behavioral, affective, and attentional disorders,
      particularly with their potential predictive capabilities, and ability to improve
      diagnosis and to decrease the associated burdens of disease. The present study
      focused specifically the perspectives of mental health providers on the role of
      neuroimaging and genetic testing in clinical practice with children and
      adolescents. METHODS: We interviewed 38 psychiatrists, psychologists, and allied
      mental health professionals who work primarily with youth about their receptivity
      toward either the use of neuroimaging or genetic testing. Interviews probed the
      role they foresee for these modalities for prediction, diagnosis, treatment
      planning, and the benefits and risks they anticipate. RESULTS: Practitioners
      anticipated three major benefits associated with clinical introduction of imaging
      and genetic testing in the mental health care for youth: (1) improved
      understanding of the brain and mental illness, (2) more accurate diagnosis than
      available through conventional clinical examination, and (3) legitimization of
      treatment plans. They also perceived three major risks: (1) misuse or
      misinterpretation of the imaging or genetic data, (2) potential adverse impacts
      on employment and insurance as adolescents reach adulthood, and (3) infringements
      on self-esteem or self-motivation. LIMITATIONS: The nature of the interview
      questions focused on the future of neuroimaging and genetic testing testing
      research in the context of clinical neuroscience. Therefore, the responses from
      interview participants are based on anticipated rather than actual experience.
      CONCLUSIONS: Continued expansion of brain imaging and genetic testing into
      clinical care will require a delicate balance of brain biology and respect for
      autonomy in the still-evolving cognitive and affective world of young
      individuals.

PMID- 25056009
TI  - NHS must tackle racial discrimination against staff and patients, report says.

PMID- 25056010
TI  - Koebner's phenomenon induced vitiligo following Nd:YAG laser epilation treatment
      in a woman with a past history of a Sutton nevus.

PMID- 25056011
TI  - Treatment of neurocysticercosis.

PMID- 25056012
TI  - Molecular surveillance for artemisinin resistance in Africa.

PMID- 25056013
TI  - Challenges to global pandemic mortality estimation.

PMID- 25056014
TI  - Bayes' 250-year-old legacy for infectious diseases.

PMID- 25056015
TI  - Infections related to totally implantable venous-access ports.

PMID- 25056016
TI  - Infections related to totally implantable venous-access ports.

PMID- 25056017
TI  - Increase in sexually transmitted infections during Europride 2013 in Marseille,
      France.

PMID- 25056018
TI  - Low-dose primaquine for falciparum malaria.

PMID- 25056019
TI  - HEV-associated cryoglobulinaemia and extrahepatic manifestations of hepatitis E.

PMID- 25056020
TI  - Acute unilateral cerebellitis, Epstein-Barr virus, and HIV.

PMID- 25056021
TI  - Orbital complications in children: differential diagnosis of a challenging
      disease.
AB  - Orbital swelling in children presents diagnostic and therapeutic challenges. Most
      are associated with acute sinusitis with complicating factors possibly including:
      amaurosis, meningitis, intracranial abscess or even cavernous sinus thrombosis.
      However not all acute orbital swelling is associated with acute sinusitis. A
      careful evaluation is critical prior to initiating therapy. Clinical records of
      49 children (27 girls, 22 boys, with an average age of 11.8 years) were
      retrospectively reviewed. Historical data evaluated included all available
      information from parents and previous treating physicians. All patients underwent
      intensive pediatric, ophthalmologic, and otorhinolaryngologic examinations.
      Computed tomography (CT scans) were additionally performed in 40 % of children.
      The results of any examinations were also evaluated. Eighteen of the 49 patients
      had an orbital complication due to acute sinusitis. All 18 had elevated body
      temperature, C-Reactive Protein (CRP) values and white blood cell counts.
      Endoscopy of the nose revealed pus in the middle meatus in each case. According
      to Chandlers' classification, ten children presented with a preseptal, and eight
      children had a postseptal orbital cellulitis. All patients were admitted to the
      hospital and treated with intravenous antibiotics. CT scans further demonstrated
      signs of subperiostal abscess in four children. Functional endoscopic sinus
      surgery (FESS) was required in six children, including all patients with
      subperiostal abscess. Twenty children experienced orbital swelling unrelated to
      acute sinusitis, i.e. atheroma, inflammed insect stings, dental related abscess,
      conjunctivitis, and Herpes simplex associated superinfection. In three children,
      acute orbital swelling was caused by an orbital tumor. Orbital complications of
      an acute sinusitis occur often in the pediatric patient group, and most of these
      patients can be treated conservative with intravenous antibiotics. Indications
      for FESS include failure to improve or worsening of clinical symptoms during 24 h
      of therapy, signs for subperiostal abscess in CT scan, and/or vision loss.
      Patients with infectous orbital complications had fever, elevated CRP and white
      blood cell counts. This symptom complex is key in making the correct diagnosis.
      Interestingly, 61 % of patients in this study demonstrated non-sinusitis related
      diseases leading to acute orbital swelling, which also required prompt
      recognition and appropriate therapy.

PMID- 25056025
TI  - The wrong kind of carbon cut.

PMID- 25056023
TI  - Developing a standardised tool for assessing personal statements.

PMID- 25056022
TI  - Effects of two amino acid substitutions in the capsid proteins on the interaction
      of two cell-adapted PanAsia-1 strains of foot-and-mouth disease virus serotype O
      with heparan sulfate receptor.
AB  - BACKGROUND: Some cell-adapted strains of foot-and-mouth disease virus (FMDV) can
      utilize heparan sulfate (HS) as a receptor to facilitate viral infection in
      cultured cells. A number of independent sites on the capsid that might be
      involved in FMDV-HS interaction have been studied. However, the previously
      reported residues do not adequately explain HS-dependent infection of two cell
      adapted PanAsia-1 strains (O/Tibet/CHA/6/99tc and O/Fujian/CHA/9/99tc) of FMDV
      serotype O. To identify the molecular determinant(s) for the interaction of
      O/Tibet/CHA/6/99tc and O/Fujian/CHA/9/99tc with HS receptor, several chimeric
      viruses and site-directed mutants were generated by using an infectious cDNA of a
      non-HS-utilizing rescued virus (Cathay topotype) as the genomic backbone.
      Phenotypic properties of these viruses were determined by plaque assays and virus
      adsorption and penetration assays in cultured cells. RESULTS: Only two of the
      rescued viruses encoding VP0 of O/Tibet/CHA/6/99tc or VP1 of O/Fujian/CHA/9/99tc
      formed plaques on wild-type Chinese hamster ovary (WT-CHO; HS+) cells, but not on
      HS-negative pgsD-677 cells. The formation of plaques by these two chimeric
      viruses on WT-CHO cells could be abolished by the introduction of single amino
      acid mutations Gln-2080 -> Leu in VP2 of O/Tibet/CHA/6/99tc and Lys-1083 -> Glu
      in VP1 of O/Fujian/CHA/9/99tc, respectively. Nonetheless, the introduced mutation
      Leu-2080 -> Gln in VP2 of O/Fujian/CHA/9/99tc for the construction of expectant
      recombinant plasmid led to non-infectious progeny virus in baby hamster kidney 21
      (BHK-21) cells, and the site-directed mutant encoding Glu-1083 -> Lys in VP1 of
      O/Tibet/CHA/6/99tc did not acquire the ability to produce plaques on WT-CHO
      cells. Significant differences in the inhibition of the infectivity of four HS
      utilizing viruses by heparin and RGD-containing peptide were observed in BHK-21
      cells. Interestingly, the chimeric virus encoding VP0 of O/Fujian/CHA/9/99tc, and
      the site-directed mutant encoding Gln-2080 -> Leu in VP2 of O/Tibet/CHA/6/99tc
      could bind to HS, but there was no expression of the 3A protein of these two
      viruses in WT-CHO cells. CONCLUSION: The results suggest that the cooperation of
      certain specific amino acid residues in the capsid proteins of these two cell
      adapted PanAsia-1 strains is essential for viral infectivity, the heparin
      affinity and the capability on FMDV-HS interaction.

PMID- 25056026
TI  - Fusion furore.

PMID- 25056027
TI  - A fate sealed.

PMID- 25056028
TI  - Chile needs better science governance and support.

PMID- 25056040
TI  - Delegates mourn MH17 passengers.

PMID- 25056041
TI  - Anger as Australia dumps carbon tax.

PMID- 25056042
TI  - Gene-hunt gain for mental health.

PMID- 25056043
TI  - China plans super collider.

PMID- 25056044
TI  - Mars slow to yield its secrets.

PMID- 25056045
TI  - Plasma physics: the fusion upstarts.

PMID- 25056046
TI  - Science and politics: Hello, Governor.

PMID- 25056051
TI  - BRAIN initiative: brain secrets cheap at twice the price.

PMID- 25056047
TI  - Medical research: treat ageing.

PMID- 25056052
TI  - Environment: China's land creation project stands firm.

PMID- 25056054
TI  - Data storage: overcome hurdles to global databases.

PMID- 25056055
TI  - Weed control: tactics to stamp out herbicide resistance.

PMID- 25056056
TI  - Schizophrenia: genesis of a complex disease.

PMID- 25056057
TI  - Earth science: rain on the parade.

PMID- 25056058
TI  - Population biology: fur seals signal their own decline.

PMID- 25056060
TI  - Solid-state physics: siphoning spins.

PMID- 25056062
TI  - Spin-transfer torque generated by a topological insulator.
AB  - Magnetic devices are a leading contender for the implementation of memory and
      logic technologies that are non-volatile, that can scale to high density and high
      speed, and that do not wear out. However, widespread application of magnetic
      memory and logic devices will require the development of efficient mechanisms for
      reorienting their magnetization using the least possible current and power. There
      has been considerable recent progress in this effort; in particular, it has been
      discovered that spin-orbit interactions in heavy-metal/ferromagnet bilayers can
      produce strong current-driven torques on the magnetic layer, via the spin Hall
      effect in the heavy metal or the Rashba-Edelstein effect in the ferromagnet. In
      the search for materials to provide even more efficient spin-orbit-induced
      torques, some proposals have suggested topological insulators, which possess a
      surface state in which the effects of spin-orbit coupling are maximal in the
      sense that an electron's spin orientation is fixed relative to its propagation
      direction. Here we report experiments showing that charge current flowing in
      plane in a thin film of the topological insulator bismuth selenide (Bi2Se3) at
      room temperature can indeed exert a strong spin-transfer torque on an adjacent
      ferromagnetic permalloy (Ni81Fe19) thin film, with a direction consistent with
      that expected from the topological surface state. We find that the strength of
      the torque per unit charge current density in Bi2Se3 is greater than for any
      source of spin-transfer torque measured so far, even for non-ideal topological
      insulator films in which the surface states coexist with bulk conduction. Our
      data suggest that topological insulators could enable very efficient electrical
      manipulation of magnetic materials at room temperature, for memory and logic
      applications. 

PMID- 25056063
TI  - Zircons reveal magma fluxes in the Earth's crust.
AB  - Magma fluxes regulate the planetary thermal budget, the growth of continents and
      the frequency and magnitude of volcanic eruptions, and play a part in the genesis
      and size of magmatic ore deposits. However, because a large fraction of the magma
      produced on the Earth does not erupt at the surface, determinations of magma
      fluxes are rare and this compromises our ability to establish a link between
      global heat transfer and large-scale geological processes. Here we show that age
      distributions of zircons, a mineral often present in crustal magmatic rocks, in
      combination with thermal modelling, provide an accurate means of retrieving magma
      fluxes. The characteristics of zircon age populations vary significantly and
      systematically as a function of the flux and total volume of magma accumulated in
      the Earth's crust. Our approach produces results that are consistent with
      independent determinations of magma fluxes and volumes of magmatic systems.
      Analysis of existing age population data sets using our method suggests that
      porphyry-type deposits, plutons and large eruptions each require magma input over
      different timescales at different characteristic average fluxes. We anticipate
      that more extensive and complete magma flux data sets will serve to clarify the
      control that the global heat flux exerts on the frequency of geological events
      such as volcanic eruptions, and to determine the main factors controlling the
      distribution of resources on our planet. 

PMID- 25056064
TI  - Climate change selects for heterozygosity in a declining fur seal population.
AB  - Global environmental change is expected to alter selection pressures in many
      biological systems, but the long-term molecular and life history data required to
      quantify changes in selection are rare. An unusual opportunity is afforded by
      three decades of individual-based data collected from a declining population of
      Antarctic fur seals in the South Atlantic. Here, climate change has reduced prey
      availability and caused a significant decline in seal birth weight. However, the
      mean age and size of females recruiting into the breeding population are
      increasing. We show that such females have significantly higher heterozygosity (a
      measure of within-individual genetic variation) than their non-recruiting
      siblings and their own mothers. Thus, breeding female heterozygosity has
      increased by 8.5% per generation over the last two decades. Nonetheless, as
      heterozygosity is not inherited from mothers to daughters, substantial
      heterozygote advantage is not transmitted from one generation to the next and the
      decreasing viability of homozygous individuals causes the population to decline.
      Our results provide compelling evidence that selection due to climate change is
      intensifying, with far-reaching consequences for demography as well as phenotypic
      and genetic variation. 

PMID- 25056065
TI  - Cell communication: stop the microbial chatter.

PMID- 25056067
TI  - Universality of core promoter elements?

PMID- 25056068
TI  - Application of surface-linked liposomal antigens to the development of vaccines
      that induce both humoral and cellular immunity.
AB  - The first characteristic identified in surface-linked liposomal antigens was the
      ability to induce antigen-specific, IgE-selective unresponsiveness. These results
      remained consistent even when different coupling procedures were employed for
      antigens with liposomes or for liposomes with different lipid components. The
      potential usefulness of surface-linked liposomal antigens for application to
      vaccine development was further investigated. During this investigation, a
      significant difference was observed in the recognition of liposomal antigens by
      antigen-presenting cells between liposomes with different lipid components, and
      this difference correlated closely with the adjuvant activity of liposomes. In
      addition to this "quantitative" difference between liposomes with differential
      lipid components, a "qualitative" difference (i.e., a differential ability to
      induce cross-presentation) was observed between liposomes with different lipid
      components. Therefore, by utilizing the ability to induce cross-presentation,
      surface-linked liposomal antigens might be used to develop virus vaccines that
      would induce cytotoxic T lymphocyte (CTL) responses. We have successfully
      developed a liposome vaccine that is capable of inducing CTL responses against
      internal antigens of influenza viruses and thus removing virus-infected cells in
      the host. This CTL-based liposomal vaccine might be applicable to the development
      of vaccines against influenza and other viruses that frequently undergo changes
      in their surface antigenic molecules. 

PMID- 25056069
TI  - Spanish flu, Asian flu, Hong Kong flu, and seasonal influenza in Japan under
      social and demographic influence: review and analysis using the two-population
      model.
AB  - When cumulative numbers of patients (X) and deaths (Y) associated with an
      influenza epidemic are plotted using the log-log scale, the plots fall on an
      ascending straight line generally expressed as logY = k(logX - logN0). For the
      2009 H1N1 influenza pandemic, the slope k was ~0.6 for Mexico and ~2 for other
      countries. The two-population model was proposed to explain this phenomenon
      (Yoshikura H. Jpn J Infect Dis. 2012;65:279-88; Yoshikura H. Jpn J Infect Dis.
      2009;62:411-2; and Yoshikura H. Jpn J Infect Dis. 2009;62:482-4). The current
      article reviews and analyzes previous influenza epidemics in Japan to examine
      whether the two-population model is applicable to them. The slope k was found to
      be ~2 for the Spanish flu during 1918-1920 and the Asian flu during 1957-1958,
      and ~1 for the Hong Kong flu and seasonal influenza prior to 1960-1961; however,
      k was ~0.6 for seasonal influenza after 1960-1961. This transition of the slope k
      of seasonal influenza plots from ~1 to ~0.6 corresponded to the shift in
      influenza mortality toward the older age groups and a drastic reduction in infant
      mortality rates due to improvements in the standard of living during the 1950s
      and 1960s. All the above observations could be well explained by reconstitution
      of the influenza epidemic based on the two-population model. 

PMID- 25056070
TI  - Genetic classification of Listeria monocytogenes serotype 4b strains, including
      epidemic clones, isolated from retail meat in the Tokyo metropolitan area.
AB  - A food-borne pathogen, Listeria monocytogenes serotype 4b, has been frequently
      isolated from patients with listeriosis, and numerous outbreaks of listeriosis
      are associated with this serotype. In the present study, we performed subtyping
      of L. monocytogenes serotype 4b strains on the basis of genetic analyses. Thirty
      four isolates of serotype 4b were classified into 8 genotypes, namely genotypes
      12, 15, 16, 17, 18, 23, 24, and 25, on the basis of the sequence for the partial
      iap gene. Genetic analyses revealed that genotype 16 and genotypes 24 and 25
      belong to epidemic clone I (ECI) and ECII, respectively, which have been
      frequently associated with listeriosis outbreaks in the United States and Europe.
      The genotype isolated most frequently from retail meats in the Tokyo metropolitan
      area was genotype 12 (52%), followed by genotype 16 (29%), which belongs to ECI.
      We suggest that ECI is a common subtype of L. monocytogenes in retail meat in the
      area under investigation. On the other hand, ECII isolates were confirmed to be
      present in retail meat in Japan but were rare. 

PMID- 25056071
TI  - Analysis of bacterial pathogens causing acute diarrhea on the basis of sentinel
      surveillance in Shanghai, China, 2006-2011.
AB  - Acute diarrhea is the most common infectious disease worldwide and its causes
      vary from one region to another. We aimed to analyze the spectrum and
      epidemiological characteristics of pathogens from 22,386 outpatients with acute
      diarrhea on the basis of surveillance data from Shanghai, China, during 2006
      2011. The following 8 pathogens were isolated and identified using standard
      methods: Salmonella, Shigella, Vibrio cholerae, V. parahaemolyticus,
      enteropathogenic Escherichia coli, enterotoxigenic E. coli, enteroinvasive E.
      coli, and enterohemorrhagic E. coli. In total, 2,234 strains of pathogens were
      obtained and the overall isolation rate of these 8 pathogens gradually decreased
      from 17.1% in 2006 to 7.4% in 2011. V. parahaemolyticus was the most frequently
      identified pathogen, followed by Shigella and Salmonella. The isolation rate of
      V. parahaemolyticus notably varied by season, whereas Salmonella and Shigella
      infections showed little seasonal variation. Age-related variation was also
      observed. V. parahaemolyticus infection occurred more often in patients aged 20
      40 years. S. enterica serovar Enteritidis and S. flexneri were the most common
      serotypes of Salmonella and Shigella, respectively. The descending trend observed
      in the isolation rate of pathogens from the current surveillance suggests an
      urgent requirement or improvement. 

PMID- 25056072
TI  - High incidence of community-acquired pneumonia among rapidly aging population in
      Japan: a prospective hospital-based surveillance.
AB  - The age-group-specific incidence and etiological patterns of community-acquired
      pneumonia (CAP) have not been fully established in Japan. A 2-year prospective
      surveillance was conducted in Kochi city, Western Japan. All CAP patients aged
      >=15 years who visited a community-based hospital were enrolled in the study.
      Clinical samples were examined by conventional bacterial culture and urinary
      antigen tests, and 6 bacterial pathogens and 16 respiratory viruses were
      identified from sputum samples by multiplex polymerase chain reaction assays. The
      age-group-specific incidence of CAP was estimated using a population-based data
      set of the total number of outpatients in the whole city. Ninety of the 131
      enrolled patients, 68.7% were positive for respiratory pathogens. Streptococcus
      pneumoniae was the leading bacterial pathogen identified (28.2%). Respiratory
      viruses were identified in 36 patients (27.5%), and human entero-rhinovirus was
      the most common (13.3%) among them. The estimated overall incidence of adult CAP
      in Kochi was 9.6 per 1,000 person-years (PY); the estimated age group-specific
      incidence was 3.4, 10.7, and 42.9 per 1,000 PY for those aged 15-64, 65-74, and
      >=75 years, respectively. The high incidence of CAP in these rural city of Japan,
      probably reflects the substantial aged population. S. pneumoniae and respiratory
      viruses play important roles in CAP in all age groups. 

PMID- 25056061
TI  - Biological insights from 108 schizophrenia-associated genetic loci.
AB  - Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a
      large number of alleles, including common alleles of small effect that might be
      detected by genome-wide association studies. Here we report a multi-stage
      schizophrenia genome-wide association study of up to 36,989 cases and 113,075
      controls. We identify 128 independent associations spanning 108 conservatively
      defined loci that meet genome-wide significance, 83 of which have not been
      previously reported. Associations were enriched among genes expressed in brain,
      providing biological plausibility for the findings. Many findings have the
      potential to provide entirely new insights into aetiology, but associations at
      DRD2 and several genes involved in glutamatergic neurotransmission highlight
      molecules of known and potential therapeutic relevance to schizophrenia, and are
      consistent with leading pathophysiological hypotheses. Independent of genes
      expressed in brain, associations were enriched among genes expressed in tissues
      that have important roles in immunity, providing support for the speculated link
      between the immune system and schizophrenia. 

PMID- 25056073
TI  - Bath water contamination with Legionella and nontuberculous mycobacteria in 24
      hour home baths, hot springs, and public bathhouses of Nagano Prefecture, Japan.
AB  - Bath water samples were collected from 116 hot springs, 197 public bathhouses,
      and 38 24-hour home baths in Nagano Prefecture, Japan, during the period of April
      2009 to November 2011, for determining the presence and extent of contamination
      with Legionella and nontuberculous mycobacteria. Cultures positive for Legionella
      were observed in 123 of the 3,314 bath water samples examined. The distribution
      and abundance of Legionella and/or combined contamination with Legionella and
      nontuberculous mycobacteria were investigated to clarify the contamination
      levels. The abundance of Legionella was demonstrated to correlate considerably
      with the levels of combined contamination with Legionella and nontuberculous
      mycobacteria. Legionella spp. were obtained from 61% of the water samples from 24
      hour home baths, but only from 3% of the samples from public bathhouses and hot
      springs. This is despite the fact that a few outbreaks of Legionnaires' disease
      in Nagano Prefecture as well as other regions of Japan have been traced to bath
      water contamination. The comparatively higher rate of contamination of the 24
      hour home baths is a matter of concern. It is therefore advisable to routinely
      implement good maintenance of the water basins, particularly of the 24-hour home
      baths. 

PMID- 25056074
TI  - A novel complex recombinant form of type 48-related human adenovirus species D
      isolated in Japan.
AB  - Recently, new genotypes of human adenoviruses (HAdVs) have been reported and many
      of them have been found to be recombinant forms of different known types of HAdV
      species D (HAdV-D). The objective of this study was to document the evolutionary
      features of a novel isolate (HAdV_Chiba_E086/2012) obtained from the eye swab of
      a patient with conjunctivitis in Japan. Viral DNA was extracted from the isolate
      to sequence the whole genome by the Sanger method and aligned with available
      genome sequences of HAdV-Ds. The phylogenetic trees of the nucleotide sequences
      of the penton base, hexon, and fiber genes and the E3 region showed that
      HAdV_Chiba_E086/2012 is closest to HAdV genotype 65 (HAdV-GT65), HAdV-48, HAdV
      GT60 and HAdV-22 at 98%, 99%, 95% and 98% identity, respectively, suggesting that
      this isolate is a novel recombinant form to be designated as P65H48F60. Further
      phylogenetic and recombination analyses of the genome alignment of the new
      isolate implied that nested recombination events involving HAdV-GT59, GT65, 48,
      GT60, 22, and some ancestral lineages or their close relatives have shaped its
      genome. These results showed that HAdV_Chiba_E086/2012 is the first HAdV-48
      related HAdV found in Japan, which has the most complicated evolutionary history
      among the known HAdVs so far. 

PMID- 25056075
TI  - Antibiotic susceptibility of Neisseria gonorrhoeae isolates from Guangzhou,
      China, during 2002-2011.
AB  - Antibiotic susceptibility of Neisseria gonorrhoeae in Guangzhou during 2002-2011
      showed that resistance to penicillin and ciprofloxacin was high, while
      ceftriaxone remained effective although there was a trend towards reduced
      sensitivity. 

PMID- 25056076
TI  - Varicella infection complicated by marked thrombocytopenia.
AB  - We report a rare case of adult varicella complicated by marked thrombocytopenia.
      A 49-year-old woman presented with fever and rash for 3 days. Blood examination
      revealed marked thrombocytopenia (2.7 * 10(4)/MUL). Varicella infection was
      diagnosed after elevated levels of varicella zoster virus IgM and IgG antibodies
      were observed 2 weeks later. In this case, thrombocytopenia was due to varicella
      infection, and the mechanism was estimated to be non-immunological. Because
      varicella infection complicated by thrombocytopenia may result in fatal bleeding,
      thrombocytopenia in patients with varicella warrants close attention. 

PMID- 25056077
TI  - Evaluation of clinical and laboratory findings of pediatric and adult patients
      with oropharyngeal tularemia in Turkey: a combination of surgical drainage and
      antibiotic therapy increases treatment success.
AB  - We analyzed the clinical and laboratory findings of both pediatric and adult
      patients with oropharyngeal tularemia. We also compared the therapeutic outcomes
      of patients who underwent surgical drainage of lymph nodes early or late during
      antibiotic therapy. A total of 68 patients with oropharyngeal tularemia,
      including 26 children and 42 adults, were enrolled in this study. The average
      duration between symptom onset and hospital admission was 20.8 days (4-60 days)
      in the pediatric group and 32.6 days (4-90 days) in the adult group (P = 0.009).
      The most frequently observed clinical symptoms were sore throat (100% and 100%),
      fever (96.2% and 90.5%), tonsillitis (69.2% and 78.6%), and rash (15.4% and
      11.9%) in the pediatric and adult groups, respectively. However, the frequencies
      of erythema, tenderness, and fluctuant of enlarged lymph nodes were significantly
      higher in the adult group than in the pediatric group (P = 0.005, P = 0.029, and
      P = 0.041, respectively). Treatment failure was observed in 2 (7.7%) pediatric
      patients and 4 (9.5%) adult patients, for a total of 6 (8.8%) treatment failures
      in the study group. Similar clinical findings and treatment outcomes were
      observed in both groups. We concluded that a combination of surgical drainage and
      antibiotic therapy increases treatment success for patients diagnosed with
      oropharyngeal tularemia. 

PMID- 25056078
TI  - The first measles outbreak caused by imported genotype D9 measles virus in
      Shandong Province, China, 2013.
AB  - This study represents a measles outbreak caused by the genotype D9 measles virus
      (MeV), which was imported by Burmese individuals. Urine and throat swab specimens
      were collected from suspected measles cases. Viruses were isolated, and a 634-bp
      target fragment of the N gene was amplified by reverse transcription-PCR and
      sequenced. Phylogenetic results indicated that the 6 isolates belonged to
      genotype D9 MeV. Through appropriate prevention and control measures, the
      transmission of genotype D9 MeV was interrupted. Genotype D9 MeV was isolated for
      the first time in Shandong and was imported by Burmese individuals. 

PMID- 25056079
TI  - The occurrence of severe rotavirus gastroenteritis in children under 3 years of
      age before and after the introduction of rotavirus vaccine: a prospective
      observational study in three pediatric clinics in Shibata City, Niigata
      Prefecture, Japan.
AB  - The occurrence of severe rotavirus gastroenteritis (RVGE) in children under 3
      years of age before and after the introduction of rotavirus vaccine was
      prospectively surveyed in three pediatric clinics in Shibata City, Niigata
      Prefecture, Japan, during the 2011 and 2012 RVGE epidemic seasons. In this
      observational study, a significantly lower occurrence of severe RVGE among severe
      gastroenteritis cases was observed in 2012. The incidence rate of severe RVGE
      among outpatients in 2012 was significantly lower than that in 2011. Despite the
      significant reduction in severe RVGE, the results must be interpreted with
      caution because the surveillance period is short and requires extension to
      conclude whether the reduction in the incidence of severe RVGE is a direct effect
      of rotavirus vaccination. Therefore, we will continue the survey to evaluate the
      impact of vaccination. 

PMID- 25056080
TI  - Stability of JC virus DNA in cerebrospinal fluid specimens preserved with
      guanidine lysis buffer for quantitative PCR testing.
AB  - Quantitative PCR testing for JC virus (JCV) DNA in the cerebrospinal fluid (CSF)
      is one of the diagnostic standards for progressive multifocal leukoencephalopathy
      (PML). The present study was conducted to examine its reliability using CSF
      specimens that had been preserved with guanidine lysis buffers in commercial
      nucleic acid extraction kits under different conditions. When CSFs were mixed
      with guanidine buffers, JCV DNA levels were not statistically reduced even after
      storage for 1 month at room temperature or for 3 months at -80C, compared with
      the control samples. In addition, the JCV DNA level was not decreased in a
      mixture of CSF and guanidine thiocyanate buffer incubated for 3 days at 56C.
      These data suggest that CSF specimens mixed with commercial guanidine buffers can
      be stored without refrigeration, more safely handled, and directly subjected to
      JCV DNA testing for PML. 

PMID- 25056081
TI  - Recent progress toward measles elimination in Hokkaido, Japan, during 2011-2012.
AB  - Laboratory diagnoses for measles were performed in a total of 97 cases in
      Hokkaido, Japan, during 2011-2012. Two patients were confirmed to be positive for
      measles virus (MV), both of whom lived in the Iburi district of Hokkaido.
      Molecular analysis of the nucleotide sequences of the nucleoprotein (N) gene
      revealed that these 2 strains had high homology with each other and belonged to
      the genotype D8. The onset interval of these cases and epidemiological data
      suggested that MV transmission had occurred between them and then terminated.
      Phylogenetic analysis of the N gene revealed that the strains identified in
      Hokkaido were classified into a cluster that contained many genotype D8 strains
      that were detected within a large area of Japan. Eventually, 9 cases were
      officially reported as measles. However, other than the abovementioned 2 cases,
      no genetic information regarding MV was obtained. In future, further active
      surveillance combined with the genetic investigation should be required in all
      suspected measles cases to verify the elimination status. 

PMID- 25056082
TI  - Antimicrobial resistance among Campylobacter isolates obtained from retail
      chicken meat and offal products in Japan.
AB  - A rapid increase in antimicrobial resistance in Campylobacter has been posing a
      serious concern for human health. In this study, we aimed to demonstrate the
      overall trend in antimicrobial resistance among Campylobacter isolates obtained
      from chicken meat and offal products collected from a wide geographic area
      throughout Japan. Resistance to Enrofloxacin was most frequently observed, with
      significantly higher rate of resistance among isolates obtained from offal
      (55.6%) than from meat (27.3%) samples (p = 0.05). These results highlight need
      for a better understanding of the characteristics of Campylobacter isolates
      obtained from chicken meat and offal products. 

PMID- 25056083
TI  - Outbreak of human metapneumovirus infection in a severe motor-and-intellectual
      disabilities ward in Japan.

PMID- 25056084
TI  - A foodborne outbreak of group A streptococcal infection in Fukuoka Prefecture,
      Japan.

PMID- 25056085
TI  - Genotyping of mumps virus strains detected in Kobe City from 1991 to 2012.

PMID- 25056086
TI  - An outbreak of acute respiratory infections due to human respiratory syncytial
      virus in a nursing home for the elderly in Ibaraki, Japan, 2014.

PMID- 25056087
TI  - Ovarian responsiveness in women receiving fertility treatment after methotrexate
      for ectopic pregnancy: a systematic review and meta-analysis.
AB  - STUDY QUESTION: Does previous methotrexate (MTX) treatment for ectopic pregnancy
      (EP) have an effect on ovarian response in women receiving fertility treatment?
      SUMMARY ANSWER: MTX treatment for EP does not seem to affect subsequent fertility
      treatment. WHAT IS KNOWN ALREADY: MTX is commonly used to treat EPs that are
      diagnosed early. Previous studies have reported conflicting results about its
      effect on subsequent fertility treatments. STUDY DESIGN, SIZE, DURATION: This
      systematic review and meta-analysis included a total of 329 patients who had
      participated in 7 observational studies. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: A search of the MEDLINE, EMBASE and PUBMED databases was conducted to
      identify studies about fertility treatments after MTX treatment for EP, published
      in English or French up to December 2013. Studies were eligible for inclusion
      only if they compared indicators of ovarian responsiveness during ART in the
      cycles before and after an injection of MTX for EP. The primary outcome measure
      was the number of oocytes retrieved. Secondary outcomes included the basal serum
      FSH level, duration of stimulation, total gonadotrophin dose and serum E2 level
      on the day of hCG triggering. MAIN RESULTS AND THE ROLE OF CHANCE: The mean
      number of oocytes retrieved during the cycles before and after the MTX treatment
      did not differ significantly (P = 0.4). The comparisons before and after MTX
      treatment of the basal plasma FSH level, the duration of stimulation, the total
      gonadotrophin dose used for stimulation and the estradiol level on the day
      ovulation was triggered did not find any significant differences. LIMITATIONS,
      REASONS FOR CAUTION: The literature on this topic is sparse, with few studies and
      even fewer of high methodological quality. WIDER IMPLICATIONS OF THE FINDINGS:
      These results indicate that MTX to treat EP in infertile patients does not have
      any negative effect on their subsequent fertility treatment, but further studies
      should be performed before this result can be considered definitive. STUDY
      FUNDING/COMPETING INTERESTS: This work received support from the Department of
      Gynecology and Obstetrics, La Conception Hospital, Marseille, France. The authors
      have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

PMID- 25056088
TI  - Anti-Mullerian hormone: correlation with testosterone and oligo- or amenorrhoea
      in female adolescence in a population-based cohort study.
AB  - STUDY QUESTIONS: Can serum anti-Mullerian hormone (AMH) levels measured in female
      adolescents predict polycystic ovary syndrome (PCOS)-associated features in
      adolescence and early adulthood? SUMMARY ANSWER: AMH levels associated well with
      PCOS-associated features (such as testosterone levels and oligoamenorrhoea) in
      adolescence, but was not an ideal marker to predict PCOS-associated features in
      early adulthood. WHAT IS KNOWN ALREADY: Several studies have reported that there
      is a strong correlation between antral follicle count and serum AMH levels and
      that women with PCOS/PCO have significantly higher serum AMH levels than women
      with normal ovaries. Other studies have reported an association between AMH serum
      levels and hyperandrogenism in adolescence, but none has prospectively assessed
      AMH as a risk predictor for developing features of PCOS during adulthood. STUDY
      DESIGN, SIZE, DURATION: A subset of 400 girls was selected from the prospective
      population-based Northern Finland Birth Cohort 1986 (n = 4567 at age 16 and n =
      4503 at age 26). The population has been followed from 1986 to the present.
      PARTICIPANTS/MATERIAL, SETTING, METHODS: At age 16, 400 girls (100 from each
      testosterone quartile: 50 with oligo- or amenorrhoea and 50 with a normal
      menstrual cycle) were selected at random from the cohort for AMH measurement.
      Metabolic parameters were also assessed at age 16 in all participants. Postal
      questionnaires enquired about oligo- or amenorrhoea, hirsutism, contraceptive use
      and reproductive health at ages 16 and 26. MAIN RESULTS AND ROLE OF CHANCE: There
      was a significant correlation between AMH and testosterone at age 16 (r = 0.36, P
      < 0.001). AMH levels at age 16 were significantly higher among girls with oligo-
      or amenorrhoea compared with girls with normal menstrual cycles (35.9 pmol/l [95%
      CI: 33.2;38.6] versus 27.7 pmol/l [95% CI: 25.0;30.4], P < 0.001). AMH at age 16
      was higher in girls who developed hirsutism at age 26 compared with the non
      hirsute group (31.4 pmol/l [95% CI 27.1;36.5] versus 25.8 pmol/l [95% CI
      23.3;28.6], P = 0.036). AMH at age 16 was also higher in women with PCOS at age
      26 compared with the non-PCOS subjects (38.1 pmol/l [95% CI 29.1;48.4] versus
      30.2 pmol/l [95% CI 27.9;32.4], P = 0.044). The sensitivity and specificity of
      the AMH (cut-off 22.5 pmol/l) for predicting PCOS at age 26 was 85.7 and 37.5%,
      respectively. The addition of testosterone did not significantly improve the
      accuracy of the test. There was no significant correlation between AMH levels and
      metabolic indices at age 16. IMPLICATIONS, REASONS FOR CAUTION: AMH is related to
      oligo- or amenorrhoea in adolescence, but it is not a good marker for metabolic
      factors. The relatively low rate of participation in the questionnaire at age 26
      may also have affected the results. AMH was measured in a subset of the whole
      cohort. AMH measurement is lacking international standardization and therefore
      the concentrations and cut-off points are method dependent. WIDER IMPLICATIONS
      FOR THE FINDINGS: Using a high enough cut-off value of AMH to predict which
      adolescents are likely to develop PCOS in adulthood could help to manage the
      condition from an early age due to a good sensitivity. However, because of its
      low specificity, it is not an ideal diagnostic marker, and its routine use in
      clinical practice cannot, at present, be recommended. STUDY FUNDINGS AND
      COMPETING INTERESTS: The study was funded by a grant from Wellcome Trust
      (089549/Z/09/Z) to H.L., S.F. and M.-R.J. Study funding was also received from
      Oulu University Hospital Research Funds, Sigrid Juselius Foundation and the
      Academy of Finland. None of the authors have any competing interest to declare.

PMID- 25056089
TI  - Molecular characterization of a Chinese family carrying a novel C4329A mutation
      in mitochondrial tRNAIle and tRNAGln genes.
AB  - BACKGROUND: Hypertension is a very common cardiovascular disease influenced by
      multiple genetic and environmental factors. More recently, there are some studies
      showed that mutations in mitochondrial DNA have been involved in its
      pathogenesis. In this study we did further investigations on this relationship.
      METHODS: Epidemiological research found a Han Chinese family with probable
      maternally transmitted hypertension. Sequence analysis of the whole mitochondrial
      DNA was detected from all the family members. And evaluations of the clinical,
      genetic and molecular characterization were also performed. RESULTS: Matrilineal
      relatives within the family exhibited varying degrees of hypertension with an
      onset age of 48-55 years. Sequence analysis of this pedigree showed a novel
      homoplasmic 4329C > G mutation located at the 3' end of the tRNAIle and tRNAGln
      genes that was absent from 366 Chinese controls. The cytosine (C) at 4329
      position was very important in the structural formation and stabilization of
      functional tRNAs, which was highly conserved in mitochondria of various organisms
      and also contributed to the high fidelity of the acceptor arm. Cells carrying
      this mutation were also shown to harbor mitochondrial dysfunctions. CONCLUSIONS:
      The C4329G point mutation in tRNAIle and tRNAGln was involved in the pathogenesis
      of hypertension, perhaps in association with other modifying factors.

PMID- 25056090
TI  - Imatinib intermediate as a two in one dual channel sensor for the recognition of
      Cu2+ and I- ions in aqueous media and its practical applications.
AB  - An imatinib intermediate, 6-methyl-N-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3
      diaminepyridopyrimidotoluidine (PPT-1), was developed for the colorimetric
      sensing of Cu(2+) ions in aqueous solution. With Cu(2+), the receptor PPT-1
      showed a highly selective naked-eye detectable color change from colorless to red
      over the seventy other tested cations. The colorimetric sensing ability of PPT-1
      was successfully utilized in the preparation of test strips and supported silica
      for the real samples analysis to detect Cu(2+) ions from 100% aqueous
      environment. Moreover, the iodide-sensing ability of receptor PPT-1 was explored
      among the ten examined anions. 

PMID- 25056092
TI  - Root length, biomass, tissue chemistry and mycorrhizal colonization following 14
      years of CO2 enrichment and 6 years of N fertilization in a warm temperate
      forest.
AB  - Root systems serve important roles in carbon (C) storage and resource acquisition
      required for the increased photosynthesis expected in CO2-enriched atmospheres.
      For these reasons, understanding the changes in size, distribution and tissue
      chemistry of roots is central to predicting the ability of forests to capture
      anthropogenic CO2. We sampled 8000 cm(3) soil monoliths in a pine forest exposed
      to 14 years of free-air-CO2-enrichment and 6 years of nitrogen (N) fertilization
      to determine changes in root length, biomass, tissue C : N and mycorrhizal
      colonization. CO2 fumigation led to greater root length (98%) in unfertilized
      plots, but root biomass increases under elevated CO2 were only found for roots <1
      mm in diameter in unfertilized plots (59%). Neither fine root [C] nor [N] was
      significantly affected by increased CO2. There was significantly less root
      biomass in N-fertilized plots (19%), but fine root [N] and [C] both increased
      under N fertilization (29 and 2%, respectively). Mycorrhizal root tip biomass
      responded positively to CO2 fumigation in unfertilized plots, but was unaffected
      by CO2 under N fertilization. Changes in fine root [N] and [C] call for further
      study of the effects of N fertilization on fine root function. Here, we show that
      the stimulation of pine roots by elevated CO2 persisted after 14 years of
      fumigation, and that trees did not rely exclusively on increased mycorrhizal
      associations to acquire greater amounts of required N in CO2-enriched plots.
      Stimulation of root systems by CO2 enrichment was seen primarily for fine root
      length rather than biomass. This observation indicates that studies measuring
      only biomass might overlook shifts in root systems that better reflect treatment
      effects on the potential for soil resource uptake. These results suggest an
      increase in fine root exploration as a primary means for acquiring additional
      soil resources under elevated CO2. 

PMID- 25056094
TI  - Reply: To PMID 23460730.

PMID- 25056093
TI  - Toxic effects of chronic mercury exposure on the retinal nerve fiber layer and
      macular and choroidal thickness in industrial mercury battery workers.
AB  - BACKGROUND: The aim of this study was to evaluate the toxic effects of mercury on
      retinal nerve fiber layer thickness (RNFLT), macular thickness (MT), and
      choroidal thickness (CT) by using spectral-domain optical coherence tomography
      (SD-OCT) in battery industry workers who had been chronically exposed to mercury.
      MATERIAL/METHODS: Battery factory workers (n=31) and healthy non-factory employee
      controls (n=15) participated in the study. Participants were divided into 3
      groups: Group 1 (n=15) was factory workers who had worked for more than 5 years
      in a mercury battery factory; Group 2 (n=16) was factory worker who had worked
      for less than 5 years in a mercury battery factory; and Group 3 (n=15) was
      healthy non-employees. Systemic symptoms were recorded. Ophthalmic examination
      included best-corrected visual acuity test, color vision test, full
      ophthalmologic examination, and SD-OCT of the RNLF, macula, and choroid. To
      determine mercury exposure, venous blood samples were collected and mercury
      levels were assessed. RESULTS: In our study group the most common systemic
      symptoms were insomnia (67.7%) and fatigue (67.7%). There were no significant
      differences between Group 1 and Group 2, but there were significant differences
      between Group 3 and both Group 1 and Group 2 in best-corrected visual acuity
      values (1=2<3), color vision scores, blood mercury levels, and duration (mean +/
      SD, range) of mercury exposure(1>2>3). OCT values of RNFLTs, MTs, and CTs of all
      3 groups were statistically different from each another (1<2<3). CONCLUSIONS: SD
      OCT can be useful for evaluating the toxic effects of chronic exposure to
      mercury.

PMID- 25056095
TI  - The statistics used in a paper on orthodontic treatment need.

PMID- 25056096
TI  - Homology and heterology of cephalometric landmarks: methodological consequences.

PMID- 25056097
TI  - How detectable is predation in stage-structured populations? Insights from a
      simulation-testing analysis.
AB  - The potential of predation to structure marine food webs is widely acknowledged.
      However, available tools to detect the regulation of prey population dynamics by
      predation are limited, partly because available population data often aggregate a
      population's age structure into a single biomass or abundance metric.
      Additionally, many food webs are relatively complex, with prey species subject to
      different assemblages of predators throughout their ontogeny. The goal of this
      study was to evaluate the extent to which stage-structured predation could be
      reliably detected from time series of total biomass of predators and prey. We
      simulated age-structured populations of four mid-trophic-level fish species with
      distinct life-history traits, exposed them to variable predation at different
      life stages and fit production models to resulting population biomass to
      determine how reliably the effects of predators could be detected. Predation
      targeting early life history and juvenile life stages generally led to larger
      fluctuations in annual production and was therefore more detectable. However,
      ecologically realistic levels of observation error and environmental
      stochasticity masked most predator signals. The addition of predation at a second
      life stage sharply decreased the ability to detect the effect of each predator.
      We conclude that the absence of detectable species interactions from biomass time
      series may be partly due to the interactive effects of environmental variability
      and complex food web linkages and life histories. We also note that predation
      signals are most robust for predator-prey systems where predators primarily act
      on mortality of submature life-history stages. Simulation testing can be applied
      widely to evaluate the statistical power of analyses to detect predation effects.

PMID- 25056098
TI  - Feasibility of automated slope III and Scond analysis in children.
AB  - BACKGROUND: Multiple breath washout (MBW) derived Scond is an established index
      of ventilation inhomogeneity. Time-consuming post hoc calculations of the
      expirogram's slope of alveolar phase III (SIII) and the lack of available
      software hampered widespread application of Scond. METHODS: Seventy-two school
      aged children (45 with cystic fibrosis; CF) performed 3 nitrogen MBW. We tested a
      new automated algorithm for Scond analysis (Scondauto ) which comprised breath
      selection for SIII detection, calculation and reporting of test quality. We
      compared Scondauto to (i) standard Scond analysis (Scondmanual ) with manual
      breath selection and to (ii) pragmatic Scond analysis including all breaths
      (Scondall ). Primary outcomes were success rate and agreement between different
      Scond protocols, and Scond fitting quality (linear regression R(2) ). RESULTS:
      Average Scondauto (0.06 for CF and 0.01 for controls) was not different from
      Scondmanual (0.06 for CF and 0.01 for controls) and showed comparable fitting
      quality (R(2) 0.53 for CF and 0.13 for controls vs. R(2) 0.54 for CF and 0.13 for
      controls). Scondall was similar in CF and controls but with inferior fitting
      quality compared to Scondauto and Scondmanual . CONCLUSIONS: Automated Scond
      calculation is feasible and produces robust results comparable to the standard
      manual way of Scond calculation. This algorithm provides a valid, fast and
      objective tool for regular use, even in children.

PMID- 25056099
TI  - Clinical utility and cost-effectiveness of CT-angiography in the diagnosis of
      nontraumatic subarachnoid hemorrhage.
AB  - INTRODUCTION: CT-angiography gains an increasing role in the initial diagnosis of
      patients with nontraumatic subarachnoid hemorrhage (SAH). However, the
      implementation of CT-angiography does not always exclude the necessity of
      conventional angiography. Our objective was to determine the practical utility
      and cost-effectiveness of CT-angiography. METHODS: All patients with nontraumatic
      subarachnoid hemorrhage admitted to our university hospital after implementation
      of CT-angiography between June 1, 2011 and June 30, 2012 were retrospectively
      analyzed in regard to factors of treatment flow, radiation exposure, harms of
      contrast medium loading, and diagnostic costs. A control group of the same size
      was assembled from previously admitted SAH patients, who did not undergo
      pretreatment CT-angiography. Furthermore, cost-effectiveness analysis was
      performed. RESULTS: The final analysis consisted of 93 patients in each group. Of
      93 patients with pretreatment CT-angiography, 74 had to undergo conventional
      angiography for diagnostic and/or therapeutic purposes. CT-angiography had
      significant impact on the reduction of collective effective radiation dose by
      4.419 mSv per person (p = 0.0002) and was not associated with additional harms.
      Despite the significantly earlier detection of aneurysms with CT-angiography (p <
      0.0001), there were no significant differences in the timing of aneurysm repair
      and duration of ICU and general hospital stay. There was an increase of
      diagnostic costs-the cost-effectiveness analysis showed, however, that benefits
      of CT-angiography in respect to radiation exposure and risk of conventional
      angiography-related complications justify the additional costs of CT-angiography.
      CONCLUSIONS: Although the implementation of CT-angiography in SAH diagnosis
      cannot completely replace conventional angiography, it can be approved in regard
      to radiation hygiene and cost-effectiveness.

PMID- 25056100
TI  - The usefulness of diffusion-weighted/fluid-attenuated inversion recovery imaging
      in the diagnostics and timing of lacunar and nonlacunar stroke.
AB  - INTRODUCTION: The DWI/FLAIR mismatch is a potential radiological marker for the
      timing of stroke onset. The aim of the study was to assess if the DWI/FLAIR
      mismatch can help to identify patients with both lacunar and nonlacunar acute
      ischemic stroke within 4.5 h of onset. METHODS: A retrospective study was
      performed in which the authors analysed data from 86 ischemic lacunar and
      nonlacunar stroke patients with a known time of symptom onset, imaged within the
      first 24 h from stroke onset (36 patients <4.5 h, 14 patients 4.5-6 h, 15
      patients 6-12 h, and 21 patients 12-24 h). Patients underwent the admission CT
      and MR scan. The presence of lesions was assessed in correlation with the
      duration of the stroke. RESULTS: The time from stroke onset to neuroimaging was
      significantly shorter in patients with an ischemic lesion visible only in the DWI
      (mean 2.78 h, n = 24) as compared to patients with signs of ischemia also in
      other modalities (mean 8.6 h, n = 62) (p = 0.0001, Kruskal-Wallis ANOVA). The
      DWI/FLAIR mismatch was characterised by a global sensitivity of 58%, specificity
      94%, PPV 87.5%, and NPV 76% in identifying patients in the 4.5 h thrombolysis
      time window. For lacunar strokes (n = 20), these parameters were as follows:
      sensitivity 50%, specificity 92.8%, PPV 75 %, and NPV 81.2%. CONCLUSIONS: The
      presence of acute ischemic lesions only in DWI can help to identify both lacunar
      and nonlacunar stroke patients who are in the 4.5 h time window for intravenous
      thrombolysis with high specificity.

PMID- 25056101
TI  - Review article: adherence to Rome criteria in therapeutic trials in functional
      dyspepsia.
AB  - BACKGROUND: The Rome criteria are currently required by health authorities for
      the inclusion of patients affected by functional dyspepsia in therapeutic trials.
      However, the degree of adherence to these criteria has not been formally
      verified. AIM: To review adherence to the Rome criteria for inclusion criteria,
      outcome measures and endpoints in therapeutic trials on functional dyspepsia and
      the potential impact on the conclusions that can be drawn from these studies.
      METHODS: A total of 1818 articles were screened. Fifty-eight trials claiming to
      include adults affected by functional dyspepsia as defined by the Rome criteria
      published as full articles in English between 2000 and 2013 were considered.
      RESULTS: Lack of full adherence to the Rome criteria of inclusion criteria was
      found in 54% of the studies, due to inclusion of patients with symptoms not
      reported in the Rome criteria or definitions of dyspeptic symptom that varied
      from those proposed by the Rome criteria. Ninety-five per cent of clinical trials
      adopted therapeutic outcome measures that were not adherent to the Rome criteria,
      using questionnaires that did not include all dyspeptic symptoms or including
      symptoms other than those proposed by the Rome criteria. CONCLUSIONS: Stringent
      criteria have not been adopted for inclusion criteria and outcome measures in the
      vast majority of published studies on functional dyspepsia that claim to have
      been carried out according to the Rome criteria. Appropriate questionnaires
      should be developed to promote adherence to internationally accepted definitions
      of the syndrome in future studies.

PMID- 25056102
TI  - Effects of oil on aqueous foams: electrical conductivity of foamed emulsions.
AB  - Three-phase foams containing dispersed oils (also called foamed emulsion) are
      usually encountered in such areas as enhanced oil recovery, food foams, and in
      foams containing antifoams. The presence of oil causes these complex fluids to
      exhibit extraordinary properties in contrast to aqueous foams. We experimentally
      investigated, for the first time, the conductive properties of the foamed
      emulsions and found that the electrical conductivity increases monotonically with
      the volumetric liquid fraction, presenting a linear relationship. Combined with
      the analysis on the foaming capacity and microstructure of this complex fluid,
      the conductive mechanism is revealed. In these foamed emulsions, the whole
      conductive network is comprised of two levels of structural hierarchy, which
      displays a different mechanism from those of the conventional aqueous foams. The
      lamella of emulsions is taken as primary electrical channel, whereas the
      secondary electrical channel occurs in the lamella between two bubbles. This
      conductive behaviour is attributed to the microstructure properties of the foamed
      emulsions. We believe that such findings are potentially important for a better
      understanding of the fundamentals of these tri-phase dispersion systems. 

PMID- 25056103
TI  - The excretion of NaCl and KCl loads in mosquitoes. 1. Control data.
AB  - The handling of Na(+) and K(+) loads was investigated in isolated Malpighian
      tubules and in whole mosquitoes of Aedes aegypti. Isolated Malpighian tubules
      bathed in Na(+)-rich Ringer solution secreted Na(+)-rich fluid, and tubules
      bathed in K(+)-rich Ringer solution secreted K(+)-rich fluid. Upon Na(+) loading
      the hemolymph, the mosquito removed 77% the injected Na(+) within the next 30
      min. The rapid onset and magnitude of this diuresis and the excretion of more
      Na(+) than can be accounted for by tubular secretion in vitro is consistent with
      the release of the calcitonin-like diuretic hormone in the mosquito to remove the
      Na(+) load from the hemolymph. Downstream, K(+) was reabsorbed with water in the
      hindgut, which concentrated Na(+) in excreted urine hyperosmotic to the
      hemolymph. Upon K(+) loading the hemolymph, the mosquito took 2 h to remove 100%
      of the injected K(+) from the hemolymph. The excretion of K(+)-rich isosmotic
      urine was limited to clearing the injected K(+) from the hemolymph with a minimum
      of Cl(-) and water. As a result, 43.3% of the injected Cl(-) and 48.1% of the
      injected water were conserved. The cation retained in the hemolymph with Cl(-)
      was probably N-methyl-d-glucamine, which replaced Na(+) in the hemolymph
      injection of the K(+) load. Since the tubular secretion of K(+) accounts for the
      removal of the K(+) load from the hemolymph, the reabsorption of K(+), Na(+), Cl(
      ), and water must be inhibited in the hindgut. The agents mediating this
      inhibition are unknown.

PMID- 25056104
TI  - Two-week normobaric intermittent hypoxia exposures enhance oxyhemoglobin
      equilibrium and cardiac responses during hypoxemia.
AB  - Intermittent hypoxia (IH) is extensively applied to challenge cardiovascular and
      respiratory function, and to induce physiological acclimatization. The purpose of
      this study was to test the hypothesis that oxyhemoglobin equilibrium and
      tachycardiac responses during hypoxemia were enhanced after 14-day IH exposures.
      Normobaric-poikilocapnic hypoxia was induced with inhalation of 10% O2 for 5-6
      min interspersed with 4 min recovery on eight nonsmokers. Heart rate (HR),
      arterial O2 saturation (SaO 2), and end-tidal O2 (PetO 2) were continuously
      monitored during cyclic normoxia and hypoxia. These variables were compared
      during the first and fifth hypoxic bouts between day 1 and day 14. There was a
      rightward shift in the oxyhemoglobin equilibrium response following 14-day IH
      exposures, as indicated by the greater PetO 2 (an index of arterial Po2) at 50%
      of SaO 2 on day 14 compared with day 1 [33.9 +/- 1.5 vs. 28.2 +/- 1.3 mmHg (P =
      0.005) during the first hypoxic bout and 39.4 +/- 2.4 vs. 31.4 +/- 1.5 mmHg (P =
      0.006) during the fifth hypoxic bout] and by the augmented gains of DeltaSaO
      2/DeltaPetO 2 (i.e., deoxygenation) during PetO 2 from 65 to 40 mmHg in the first
      (1.12 +/- 0.08 vs. 0.80 +/- 0.02%/mmHg, P = 0.001) and the fifth (1.76 +/- 0.31
      vs. 1.05 +/- 0.06%/mmHg, P = 0.024) hypoxic bouts. Repetitive IH exposures
      attenuated (P = 0.049) the tachycardiac response to hypoxia while significantly
      enhancing normoxic R-R interval variability in low-frequency and high-frequency
      spectra without changes in arterial blood pressure at rest or during hypoxia. We
      conclude that 14-day IH exposures enhance arterial O2 delivery and improve vagal
      control of HR during hypoxic hypoxemia. 

PMID- 25056105
TI  - In vitro assessment of mouse fetal abdominal aortic vascular function.
AB  - Fetal growth restriction (FGR) affects 3-8% of human pregnancies. Mouse models
      have provided important etiological data on FGR; they permit the assessment of
      treatment strategies on the physiological function of both mother and her
      developing offspring. Our study aimed to 1) develop a method to assess vascular
      function in fetal mice and 2) as a proof of principle ascertain whether a high
      dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected
      fetal vascular reactivity. We developed a wire myography methodology for
      evaluation of fetal vascular function in vitro using the placenta-specific
      insulin-like growth factor II (Igf2) knockout mouse (P0; a model of FGR).
      Vascular function was determined in abdominal aortas isolated from P0 and wild
      type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams
      received SC 0.8 mg/ml via drinking water from E12.5; data were compared with
      water-only controls. Using wire myography, we found that fetal aortic rings
      exhibited significant agonist-induced contraction, and endothelium-dependent and
      endothelium-independent relaxation. Sex-specific alterations in reactivity were
      noted in both strains. Maternal treatment with SC significantly attenuated
      endothelium-dependent and endothelium-independent relaxation of fetal aortic
      rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents.
      Study of these vessels in mouse genetic models of pregnancy complications may 1)
      help to delineate early signs of abnormal vascular reactivity and 2) inform
      whether treatments given to the mother during pregnancy may impact upon fetal
      vascular function. 

PMID- 25056107
TI  - Abstracts from the ICBM 2014 Meeting, August 14-17, 2014, Brainerd, Minnesota.

PMID- 25056108
TI  - Pidilizumab in the treatment of diffuse large B-cell lymphoma.
AB  - INTRODUCTION: The programmed death-1 (PD-1) immune checkpoint pathway is an
      emerging target in the treatment of hematologic malignancies. Pidilizumab is an
      mAb that binds to PD-1 and is a safe and well-tolerated therapy. Recent data have
      shown clinical activity utilizing this strategy in diffuse large B-cell lymphoma
      (DLBCL). AREAS COVERED: The role of PD-1 expression in hematologic malignancies
      is explored. Recent clinical trials including the results of a Phase I trial in
      hematologic malignancies and a Phase II trial of pidilizumab following autologous
      hematopoietic stem-cell transplant (AHSCT) are reviewed. EXPERT OPINION: We
      review data that suggest that PD-1 is a promising target in the treatment and
      management of DLBCL. Changes in immune subsets following administration of
      pidilizumab are felt to represent on-target responses. The improvement in
      progression-free survival (PFS) following AHSCT supports a response to therapy.
      Importantly, the improvement in PFS for patients with positive FDG-PET/CT
      following AHSCT indicating residual disease further supports direct activity of
      pidilizumab in DLBCL.

PMID- 25056109
TI  - The effect of pain on involuntary and voluntary capture of attention.
AB  - BACKGROUND: There is converging evidence for the notion that pain affects a broad
      range of attentional domains. This study investigated the influence of pain on
      the involuntary capture of attention as indexed by the P3a component in the event
      related potential derived from the electroencephalogram. METHODS: Participants
      performed in an auditory oddball task in a pain-free and a pain condition during
      which they submerged a hand in cold water. Novel, infrequent and unexpected
      auditory stimuli were presented randomly in a series of frequent standard and
      infrequent target tones. P3a and P3b amplitudes were observed to novel,
      unexpected and target-related stimuli, respectively. RESULTS: Both
      electrophysiological components were characterized by reduced amplitudes in the
      pain compared with the pain-free condition. Hit rate and reaction time to target
      stimuli did not differ between the two conditions presumably because the
      experimental task was not difficult enough to exceed attentional capacities under
      pain conditions. CONCLUSIONS: These results indicate that voluntary attention
      serving the maintenance and control of ongoing information processing (reflected
      by the P3b amplitude) is impaired by pain. In addition, the involuntary capture
      of attention and orientation to novel, unexpected information (measured by the
      P3a) is also impaired by pain. Thus, neurophysiological measures examined in this
      study support the theoretical positions proposing that pain can reduce
      attentional processing capacity. These findings have potentially important
      implications at the theoretical level for our understanding of the interplay of
      pain and cognition, and at the therapeutic level for the clinical treatment of
      individuals experiencing ongoing pain.

PMID- 25056106
TI  - Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule
      Kir channel modulator VU573 and its inactive analog VU342.
AB  - The effect of two small molecules VU342 and VU573 on renal functions in the
      yellow fever mosquito Aedes aegypti was investigated in vitro and in vivo. In
      isolated Malpighian tubules, VU342 (10 MUM) had no effect on the transepithelial
      secretion of Na(+), K(+), Cl(-), and water. In contrast, 10 MUM VU573 first
      stimulated and then inhibited the transepithelial secretion of fluid when the
      tubules were bathed in Na(+)-rich or K(+)-rich Ringer solution. The early
      stimulation was blocked by bumetanide, suggesting the transient stimulation of Na
      K-2Cl cotransport, and the late inhibition of fluid secretion was consistent with
      the known block of AeKir1, an Aedes inward rectifier K(+) channel, by VU573.
      VU342 and VU573 at a hemolymph concentration of about 11 MUM had no effect on the
      diuresis triggered by hemolymph Na(+) or K(+) loads. VU342 at a hemolymph
      concentration of 420 MUM had no effect on the diuresis elicited by hemolymph
      Na(+) or K(+) loads. In contrast, the same concentration of VU573 significantly
      diminished the Na(+) diuresis by inhibiting the urinary excretion of Na(+), Cl(
      ), and water. In K(+)-loaded mosquitoes, 420 MUM VU573 significantly diminished
      the K(+) diuresis by inhibiting the urinary excretion of K(+), Na(+), Cl(-), and
      water. We conclude that 1) the effects of VU573 observed in isolated Malpighian
      tubules are overwhelmed in vivo by the diuresis triggered with the coinjection of
      Na(+) and K(+) loads, and 2) at a hemolymph concentration of 420 MUM VU573
      affects Kir channels systemically, including those that might be involved in the
      release of diuretic hormones.

PMID- 25056110
TI  - Structural and functional features of Crl proteins and identification of
      conserved surface residues required for interaction with the RpoS/sigmaS subunit
      of RNA polymerase.
AB  - In many gamma-proteobacteria, the RpoS/sigmaS sigma factor associates with the
      core RNAP (RNA polymerase) to modify global gene transcription in stationary
      phase and under stress conditions. The small regulatory protein Crl stimulates
      the association of sigmaS with the core RNAP in Escherichia coli and Salmonella
      enterica serovar Typhimurium, through direct and specific interaction with
      sigmaS. The structural determinants of Crl involved in sigmaS binding are
      unknown. In the present paper we report the X-ray crystal structure of the
      Proteus mirabilis Crl protein (CrlPM) and a structural model for Salmonella
      Typhimurium Crl (CrlSTM). Using a combination of in vivo and in vitro assays, we
      demonstrated that CrlSTM and CrlPM are structurally similar and perform the same
      biological function. In the Crl structure, a cavity enclosed by flexible arms
      contains two patches of conserved and exposed residues required for sigmaS
      binding. Among these, charged residues that are likely to be involved in
      electrostatic interactions driving Crl-sigmaS complex formation were identified.
      CrlSTM and CrlPM interact with domain 2 of sigmaS with the same binding
      properties as with full-length sigmaS. These results suggest that Crl family
      members share a common mechanism of sigmaS binding in which the flexible arms of
      Crl might play a dynamic role. 

PMID- 25056112
TI  - ZSM-5 zeolite nanosheets with improved catalytic activity synthesized using a new
      class of structure-directing agents.
AB  - A new series of multiquaternary ammonium structure-directing agents, based on 1,4
      diazabicyclo[2.2.2]octane, was prepared. ZSM-5 zeolites with nanosheet morphology
      (10 nm crystal thickness) were synthesized under hydrothermal conditions using
      multiquaternary ammonium surfactants as the zeolite structure-generating agents.
      Both wide-angle and small-angle diffraction patterns were obtained using only a
      suitable structure-directing agent under a specific zeolite synthesis
      composition. A mechanism of zeolite formation is proposed based on the results
      obtained from various physicochemical characterizations. ZSM-5 materials were
      investigated in catalytic reactions requiring medium to strong acidity, which are
      important for the synthesis of a wide range of industrially important fine and
      specialty chemicals. The catalytic activity of ZSM-5 materials was compared with
      that of the conventional ZSM-5 and amorphous mesoporous aluminosilicate Al-MCM
      41. The synthesis strategy of the present investigation using the new series of
      structure-directing agents could be extended for the synthesis of other related
      zeolites or other porous materials in the future. Zeolite with a structural
      feature as small as the size of a unit cell (5-10 nm) with hierarchically ordered
      porous structure would be very promising for catalysis. 

PMID- 25056111
TI  - Reprogramming ovarian and breast cancer cells into non-cancerous cells by low
      dose metformin or SN-38 through FOXO3 activation.
AB  - Cancer is a leading cause of death worldwide. Because the cytotoxic effects of
      conventional chemotherapies often harm normal tissue cells along with cancer
      cells, conventional chemotherapies cause many unwanted or intolerable side
      effects. Thus, there is an unmet medical need to establish a paradigm of
      chemotherapy-induced differentiation of cancer cells with tolerable side effects.
      Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in
      ovarian and breast cancer cells and suppresses their tumor growth in vivo. Low
      dose metformin or SN-38 increases FOXO3 nuclear localization as well as the
      amount of DNA damage markers and downregulates the expression of a cancer
      stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c
      Myc, in these cancer cells. This treatment also inhibits spheroid body-formation
      in 3-dimensional culture. In contrast, silencing FOXO3 diminishes all these
      cellular events when ovarian/breast cancer cells are treated with the mentioned
      drugs. These results suggest that low-dose metformin or SN-38 may reprogram these
      cancer cells into non-cancerous cells in a FOXO3-dependent manner, and may allow
      patients to overcome these cancers with minimal side effects. 

PMID- 25056113
TI  - Development of a small molecule probe capable of discriminating cysteine,
      homocysteine, and glutathione with three distinct turn-on fluorescent outputs.
AB  - The simultaneous discrimination of Cys, Hcy, and GSH by a single probe is still
      an unmet challenge. The design and synthesis of a small molecule probe MeO-BODIPY
      Cl (BODIPY=boron dipyrromethene) is presented, which can allow Cys, Hcy, and GSH
      to be simultaneously discriminated on the basis of three distinct fluorescence
      turn-on responses. The probe reacts with these thiols to form sulfenyl
      substituted BODIPY, which is followed by intramolecular displacement to yield
      amino-substituted BODIPY. The kinetic rate of the intramolecular displacement
      reaction determines the observed different sensing behavior. Therefore, the probe
      responds to Cys, Hcy, and GSH with fluorescence turn-on colors of yellow, yellow
      and red, and red, respectively. With this promising feature in hand, the probe
      was successfully used in imaging of Cys, Hcy and GSH in living cells. 

PMID- 25056114
TI  - Conjugation to albumin-binding molecule tags as a strategy to improve both
      efficacy and pharmacokinetic properties of the complement inhibitor compstatin.
AB  - The compstatin family of complement inhibitors has shown promise in various
      immuno-inflammatory disorders. Although recent analogues show beneficial
      pharmacokinetics, further extension of the plasma half-life is expected to
      benefit systemic application of these peptidic inhibitors. We therefore
      synthesized conjugates of compstatin analogues and albumin-binding molecules
      (ABM) to increase circulatory residence. Equilibrium dialysis in complement
      depleted serum showed a marked increase in plasma protein binding from <8 % to
      >99 % for a resulting chimera (ABM2-Cp20). Further analysis confirmed interaction
      with albumin from different species, primarily via site II. Importantly, ABM2
      Cp20 bound 20-fold stronger to its target protein C3b (KD =150 pM) than the
      parent peptide. Kinetic and in silico analysis suggested that ABM2 occupies a
      secondary site on C3b and improves the dissociation rate via additional contacts.
      Addition of an ABM modifier thereby not only improved plasma protein binding but
      also produced the most potent compstatin analogue to date with potential
      implications for the treatment of systemic complement-related diseases. 

PMID- 25056115
TI  - PACAP is essential for the adaptive thermogenic response of brown adipose tissue
      to cold exposure.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely
      distributed neuropeptide that acts as a neurotransmitter, neuromodulator,
      neurotropic factor, neuroprotectant, secretagogue, and neurohormone. Owing to its
      pleiotropic biological actions, knockout of Pacap (Adcyap1) has been shown to
      induce several abnormalities in mice such as impaired thermoregulation. However,
      the underlying physiological and molecular mechanisms remain unclear. A previous
      report has shown that cold-exposed Pacap null mice cannot supply appropriate
      levels of norepinephrine (NE) to brown adipocytes. Therefore, we hypothesized
      that exogenous NE would rescue the impaired thermogenic response of Pacap null
      mice during cold exposure. We compared the adaptive thermogenic capacity of
      Pacap(-/-) to Pacap(+/+) mice in response to NE when housed at room temperature
      (24  degrees C) and after a 3.5-week cold exposure (4  degrees C). Biochemical
      parameters, expression of thermogenic genes, and morphological properties of
      brown adipose tissue (BAT) and white adipose tissue (WAT) were also
      characterized. Results showed that there was a significant effect of temperature,
      but no effect of genotype, on the resting metabolic rate in conscious,
      unrestrained mice. However, the normal cold-induced increase in the basal
      metabolic rate and NE-induced increase in thermogenesis were severely blunted in
      cold-exposed Pacap(-/-) mice. These changes were associated with altered
      substrate utilization, reduced beta3-adrenergic receptor (beta3-Ar (Adrb3)) and
      hormone-sensitive lipase (Hsl (Lipe)) gene expression, and increased fibroblast
      growth factor 2 (Fgf2) gene expression in BAT. Interestingly, Pacap(-/-) mice had
      depleted WAT depots, associated with upregulated uncoupling protein 1 expression
      in inguinal WATs. These results suggest that the impairment of adaptive
      thermogenesis in Pacap null mice cannot be rescued by exogenous NE perhaps in
      part due to decreased beta3-Ar-mediated BAT activation. 

PMID- 25056116
TI  - Low-dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent
      osteopenic mice.
AB  - Intermittent administration of parathyroid hormone (PTH) 1-34 at a standard dose
      has been shown to induce anabolic effects in bone. However, whether low-dose PTH
      promotes bone formation during senescence is unknown. To address this issue, we
      determined the effects of low-dose PTH and analysed the underlying mechanisms in
      prematurely senescent mice that display osteopenia. Treatment of 9-week-old Samp6
      mice for 6 weeks with PTH at a standard dose (100 MUg/kg per day) increased
      vertebral and femoral bone mass and improved bone microarchitecture as a result
      of increased bone-forming surfaces and mineral apposition rate (MAR). At a
      tenfold lower dose (10 MUg/kg per day), PTH increased axial bone volume and
      trabecular thickness, as detected by bone histomorphometry but not by micro
      computed tomography analysis. This anabolic effect resulted from increased
      osteoblast activity, as reflected by increased serum N-terminal propeptide of
      type 1 procollagen (P1NP) levels and MAR, with unchanged bone-forming surface or
      osteoblast surface. Mechanistically, low-dose PTH increased the expression of
      osteoblast markers in bone marrow stromal cells and mature osteoblasts, which was
      associated with increased expression of the Wnt effector Wisp1. Moreover, low
      dose PTH decreased the expression of the Mef2c transcription factor, resulting in
      decreased Sost expression in osteoblasts/osteocytes. These results indicate that
      PTH at a low dose is effective at promoting bone formation and increased bone
      volume in senescent osteopenic mice through increased osteoblast activity and
      modulation of specific Wnt effectors, which raises the potential therapeutic use
      of intermittent PTH at low dose to increase bone forming activity and bone mass
      in skeletal senescence. 

PMID- 25056117
TI  - Metabolic phenotyping guidelines: assessing glucose homeostasis in rodent models.
AB  - The pathophysiology of diabetes as a disease is characterised by an inability to
      maintain normal glucose homeostasis. In type 1 diabetes, this is due to
      autoimmune destruction of the pancreatic beta-cells and subsequent lack of
      insulin production, and in type 2 diabetes it is due to a combination of both
      insulin resistance and an inability of the beta-cells to compensate adequately
      with increased insulin release. Animal models, in particular genetically modified
      mice, are increasingly being used to elucidate the mechanisms underlying both
      type 1 and type 2 diabetes, and as such the ability to study glucose homeostasis
      in vivo has become an essential tool. Several techniques exist for measuring
      different aspects of glucose tolerance and each of these methods has distinct
      advantages and disadvantages. Thus the appropriate methodology may vary from
      study to study depending on the desired end-points, the animal model, and other
      practical considerations. This review outlines the most commonly used techniques
      for assessing glucose tolerance in rodents and details the factors that should be
      taken into account in their use. Representative scenarios illustrating some of
      the practical considerations of designing in vivo experiments for the measurement
      of glucose homeostasis are also discussed. 

PMID- 25056118
TI  - 20 years of leptin: role of leptin in human reproductive disorders.
AB  - Leptin, as a key hormone in energy homeostasis, regulates neuroendocrine
      function, including reproduction. It has a permissive role in the initiation of
      puberty and maintenance of the hypothalamic-pituitary-gonadal axis. This is
      notable in patients with either congenital or acquired leptin deficiency from a
      state of chronic energy insufficiency. Hypothalamic amenorrhea is the best
      studied, with clinical trials confirming a causative role of leptin in
      hypogonadotropic hypogonadism. Implications of leptin deficiency have also
      emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other
      end of the spectrum, hyperleptinemia may play a role in hypogonadism associated
      with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these
      conditions of energy excess, mechanisms of reproductive dysfunction include
      central leptin resistance as well as direct effects at the gonadal level. Thus,
      reproductive dysfunction due to energy imbalance at both ends can be linked to
      leptin. 

PMID- 25056119
TI  - The RAC1 P29S hotspot mutation in melanoma confers resistance to pharmacological
      inhibition of RAF.
AB  - Following mutations in BRAF and NRAS, the RAC1 c.85C>T single-nucleotide variant
      (SNV) encoding P29S amino acid change represents the next most frequently
      observed protein-coding hotspot mutation in melanoma. However, the biologic and
      clinical significance of the RAC1 P29S somatic mutation in approximately 4% to 9%
      of patients remains unclear. Here, we demonstrate that melanoma cell lines
      possessing the RAC1 hotspot variant are resistant to RAF inhibitors (vemurafenib
      and dabrafenib). Enforced expression of RAC1 P29S in sensitive BRAF-mutant
      melanoma cell lines confers resistance manifested by increased viability,
      decreased apoptosis, and enhanced tumor growth in vivo upon treatment with RAF
      inhibitors. Conversely, RNAi-mediated silencing of endogenous RAC1 P29S in a
      melanoma cell line with a co-occurring BRAF V600 mutation increased sensitivity
      to vemurafenib and dabrafenib. Our results suggest RAC1 P29S status may offer a
      predictive biomarker for RAF inhibitor resistance in melanoma patients, where it
      should be evaluated clinically.

PMID- 25056120
TI  - Runx2 is a novel regulator of mammary epithelial cell fate in development and
      breast cancer.
AB  - Regulators of differentiated cell fate can offer targets for managing cancer
      development and progression. Here, we identify Runx2 as a new regulator of
      epithelial cell fate in mammary gland development and breast cancer. Runx2 is
      expressed in the epithelium of pregnant mice in a strict temporally and
      hormonally regulated manner. During pregnancy, Runx2 genetic deletion impaired
      alveolar differentiation in a manner that disrupted alveolar progenitor cell
      populations. Conversely, exogenous transgenic expression of Runx2 in mammary
      epithelial cells blocked milk production, suggesting that the decrease in
      endogenous Runx2 observed late in pregnancy is necessary for full
      differentiation. In addition, overexpression of Runx2 drove epithelial-to
      mesenchymal transition-like changes in normal mammary epithelial cells, whereas
      Runx2 deletion in basal breast cancer cells inhibited cellular phenotypes
      associated with tumorigenesis. Notably, loss of Runx2 expression increased tumor
      latency and enhanced overall survival in a mouse model of breast cancer, with
      Runx2-deficient tumors exhibiting reduced cell proliferation. Together, our
      results establish a previously unreported function for Runx2 in breast cancer
      that may offer a novel generalized route for therapeutic interventions. Cancer
      Res; 74(18); 5277-86. (c)2014 AACR. 

PMID- 25056121
TI  - Ubiquitin-like protein FAT10 promotes the invasion and metastasis of
      hepatocellular carcinoma by modifying beta-catenin degradation.
AB  - The ubiquitin-like protein FAT10 and the homeobox protein HOXB9 each promote
      metastatic progression in hepatocellular carcinoma (HCC). In this study, we
      investigated the clinicopathologic significance of FAT10 and HOXB9 in HCC and
      investigated a mechanistic role for FAT10 in HOXB9-mediated invasiveness and
      metastasis. Relative to adjacent normal tissues, FAT10 and HOXB9 were markedly
      overexpressed in HCC, where a positive correlation in their expression and
      associated malignant characteristics were found. RNAi-mediated silencing of FAT10
      decreased HOXB9 expression and inhibited HCC invasion and metastasis in vitro and
      in vivo. The effects of FAT10 silencing were reversed by HOXB9 overexpression,
      whereas RNAi-mediated silencing of HOXB9 decreased HCC invasion and metastasis
      driven by FAT10 overexpression. Mechanistically, FAT10 regulated HOXB9 expression
      by modulating the beta-catenin/TCF4 pathway, directly binding to beta-catenin and
      preventing its ubiquitination and degradation. Together, our results identified a
      novel HCC regulatory circuit involving FAT10, beta-catenin/TCF4, and HOXB9, the
      dysfunction of which drives invasive and metastatic character in HCC. Cancer Res;
      74(18); 5287-300. (c)2014 AACR. 

PMID- 25056122
TI  - RB family tumor suppressor activity may not relate to active silencing of E2F
      target genes.
AB  - The retinoblastoma protein pRB and its two homologs p130 and p107 form the family
      of pocket proteins and play a major role in cell-cycle regulation and suppression
      of human and mouse tumorigenesis. Pocket proteins regulate the activity of E2F
      transcription factors during G1-S transition. Two mechanisms have been described:
      (i) pocket protein binding blocks the transactivation domain of activator E2Fs,
      inhibiting E2F-dependent transcription and (ii) E2F-bound pocket proteins can
      recruit chromatin remodeling proteins containing an LxCxE motif (x encoding any
      amino acid), resulting in active repression of E2F target genes. To investigate
      the importance of pRB's LxCxE-interacting motif in cell-cycle control and tumor
      suppression, we generated mouse embryonic fibroblasts and mice expressing a
      mutant pRB protein carrying an asparagine for phenylalanine substitution at
      position 750, abrogating LxCxE binding. Because p130 may compensate for loss of
      pRB, we studied pRB(N750F) activity in the presence and absence of p130. The pRB
      LxCxE interaction was not required for cell-cycle arrest upon mitogen deprivation
      and cell-cell contact, but did contribute to RAS(V12)- and radiation-induced cell
      cycle arrest. Remarkably, the pRB-LxCxE interaction was not required for
      suppression of in vitro and in vivo transformation, even in the absence of p130.
      These results indicate that pRB's tumor suppressor activity is not effectuated by
      active silencing of E2F target genes, but rather by regulation of activator E2Fs
      or another unidentified mechanism. Furthermore, the in vitro response of pocket
      protein-perturbed cells to mitogen deprivation and cell-cell contact seems a
      better predictor of tumor development than the response to ectopic RAS(V12)
      expression. Cancer Res; 74(18); 5266-76. (c)2014 AACR. 

PMID- 25056124
TI  - The International Journal of Neuropsychopharmacology. Effects of opiates.
      Editorial.

PMID- 25056123
TI  - Evidence supporting the existence of a NUPR1-like family of helix-loop-helix
      chromatin proteins related to, yet distinct from, AT hook-containing HMG
      proteins.
AB  - NUPR1, a small chromatin protein, plays a critical role in cancer development,
      progression, and resistance to therapy. Here, using a combination of structural
      bioinformatics and molecular modeling methods, we report several novel findings
      that enhance our understanding of the biochemical function of this protein. We
      find that NUPR1 has been conserved throughout evolution, and over time it has
      undergone duplications and transpositions to form other transcriptional
      regulators. Using threading, homology-based molecular modeling, molecular
      mechanics calculations, and molecular dynamics simulations, we generated
      structural models for four of these proteins: NUPR1a, NUPR1b, NUPR2, and the NUPR
      like domain of GTF2-I. Comparative analyses of these models combined with
      extensive linear motif identification reveal that these four proteins, though
      similar in their propensities for folding, differ in size, surface changes, and
      sites amenable for posttranslational modification. Lastly, taking NUPR1a as the
      paradigm for this family, we built models of a NUPR-DNA complex. Additional
      structural comparisons revealed that NUPR1 defines a new family of small-groove
      binding proteins that share structural features with, yet are distinct from,
      helix-loop-helix AT-hook-containing HMG proteins. These models and inferences
      should lead to a better understanding of the function of this group of chromatin
      proteins, which play a critical role in the development of human malignant
      diseases. 

PMID- 25056125
TI  - Response of laying hens to feeding low-protein amino acid-supplemented diets
      under high ambient temperature: performance, egg quality, leukocyte profile,
      blood lipids, and excreta pH.
AB  - An experiment was conducted to determine whether, by using a low-protein amino
      acid-supplemented diet, the health status, stress response, and excreta quality
      could be improved without affecting the productive performance of heat-stressed
      laying hens. The requirements for egg production, egg mass, and feed conversion
      ratio were also estimated using second-order equations and broken-line
      regression. A total of 150 Lohmann Selected Leghorn (LSL-Lite) hens were divided
      randomly into five groups of 30 with five replicates of six hens. The hens were
      raised for an 8-week period (52 to 60 weeks) in wire cages situated in high
      ambient temperature in an open-sided housing system. The five experimental diets
      (ME; 2,720 kcal/kg) varied according to five crude protein (CP) levels: normal-CP
      diet (control, 16.5 % CP) and low-CP diets containing 15.0, 13.5, 12.0, or 10.5 %
      CP. All experimental diets were supplemented with crystalline amino acids at the
      levels sufficient to meet their requirements. The results showed that under high
      temperature conditions, all productive performance and egg quality parameters in
      the birds fed with 15.0, 13.5, and 12.0 % CP diets were similar to those of birds
      fed with control diet (16.5 % CP), whereas feeding 10.5 % CP diet significantly
      decreased egg production and egg mass. Estimations of requirements were of 13.93
      and 12.77 % CP for egg production, 14.62 and 13.22 % CP for egg mass, and 12.93
      and 12.26 % CP for feed conversion ratio using quadratic and broken-line models,
      respectively. Egg yolk color index, blood triglyceride level, and excreta acidity
      were also significantly higher in birds fed with 12.0 and 10.5 % CP diets
      compared with those of control birds. The heterophil to lymphocyte ratio, as a
      stress indicator, was significantly decreased by 15.0, 13.5, and 12 % CP diets.
      On the basis of our findings, reducing dietary CP from 16.5 to 12.0 % and
      supplementing the diets with the essential amino acids showed merit for improving
      the stress response and excreta quality while maintaining acceptable production
      performance from laying hens under high ambient temperature conditions.

PMID- 25056126
TI  - Meteorological variables affect fertility rate after intrauterine artificial
      insemination in sheep in a seasonal-dependent manner: a 7-year study.
AB  - A total number of 48,088 artificial inseminations (AIs) have been controlled
      during seven consecutive years in 79 dairy sheep Spanish farms (41 degrees  N).
      Mean, maximum and minimum ambient temperatures (Ts), temperature amplitude (TA),
      mean relative humidity (RH), mean solar radiation (SR) and total rainfall of each
      insemination day and 15 days later were recorded. Temperature-humidity index
      (THI) and effective temperature (ET) have been calculated. A binary logistic
      regression model to estimate the risk of not getting pregnant compared to getting
      pregnant, through the odds ratio (OR), was performed. Successful winter
      inseminations were carried out under higher SR (P < 0.01) and summer
      inseminations under lower SR values (P < 0.05). Successful inseminations during
      the summer were performed under significantly lower maximum T (P < 0.01), while
      winter inseminations resulted in pregnancy when they were carried out under
      higher maximum (P < 0.05) and minimum Ts (P < 0.01). Up to five meteorological
      variables presented OR >1 (maximum T, ET and rainfall on AI day, and ET and
      rainfall on day 15), and two variables presented OR <1 (SR on AI day and maximum
      T on day 15). However, the effect of meteorological factors affected fertility in
      opposite ways, so T becomes a protective or risk factor on fertility depending on
      season. In conclusion, the percentage of pregnancy after AI in sheep is
      significantly affected by meteorological variables in a seasonal-dependent
      manner, so the parameters such as temperature reverse their effects in the hot or
      cold seasons. A forecast of the meteorological conditions could be a useful tool
      when AI dates are being scheduled.

PMID- 25056127
TI  - Effects of climate change on the economic output of the Longjing-43 tea tree,
      1972-2013.
AB  - Based on phenological and economic output models established and meteorological
      data from 1972 to 2013, changes in the phenology, frost risk, and economic output
      of the Longjing-43 tea tree in the Yuezhou Longjing tea production area of China
      were evaluated. As the local climate has changed, the beginning dates of tea bud
      and leaf plucking of this cultivar in all five counties studied has advanced
      significantly by -1.28 to -0.88 days/decade, with no significant change in the
      risk of frost. The main tea-producing stages in the tea production cycle include
      the plucking periods for superfine, grade 1, and grade 2 buds and leaves. Among
      the five bud and leaf grades, the economic output of the plucking periods for
      superfine and grade 1 decreased significantly, that for grade 2 showed no
      significant change, and those for grades 3 and 4 increased significantly. The
      economic output of large-area tea plantations employing an average of 45 workers
      per hectare and producing superfine to grade 2 buds and leaves were significantly
      reduced by 6,745-8,829 yuan/decade/ha, depending on the county. Those tea farmers
      who planted tea trees on their own small land holdings and produced superfine to
      grade 4 tea buds and leaves themselves experienced no significant decline in
      economic output.

PMID- 25056128
TI  - Acinetobacter junii as an aetiological agent of corneal ulcer.
AB  - Rods of the Acinetobacter genus are present mainly in the external environment
      (e.g. water, soil) and in animals, while in humans they may comprise
      physiological flora. The main pathogenic species is Acinetobacter baumannii
      complex, which constitutes a common cause of nosocomial infections, particularly
      in patients with underlying diseases and risk factors (e.g. prior broad-spectrum
      antibiotic therapy, malignancy, central venous catheter, mechanical ventilation);
      however, infections of the eye caused by strains of Acinetobacter spp. are very
      rare. We report a unique case of community-acquired corneal ulcer caused by
      Acinetobacter non-baumannii (possibly A. junii), in a patient with no risk
      factors identified. The case highlights the need for obtaining a sample from the
      cornea for bacteriological culture in the case of suspected ophthalmic infection
      as identification of the pathogen, and assessment of its susceptibility profile
      enables proper antibiotic therapy, improves the outcome and may constitute an
      eyesight-saving management. 

PMID- 25056129
TI  - Minimum spread of the new Swedish variant of Chlamydia trachomatis and
      distribution of C. trachomatis ompA genotypes in three geographically distant
      areas of Spain, 2011-2012.
AB  - PURPOSE: The aim of this study was to determine the presence of the new Swedish
      Chlamydia trachomatis (C. trachomatis) variant (nvCT) and the distribution of C.
      trachomatis ompA genotypes in three geographically distant regions of Spain.
      METHODS: The genotypes of strains causing 624 episodes of infection (January 2011
      September 2012) were studied using a nested PCR that amplifies a fragment of the
      ompA gene, followed by sequencing. To detect nvCT, a real-time PCR was used that
      amplifies a fragment of the cryptic plasmid with a 377 base pair deletion, which
      identifies the nvCT. RESULTS AND CONCLUSION: The ompA genotype was identified in
      565 (90.5%) episodes. Eleven genotypes were detected, of which nine were found in
      all three regions. Only one nvCT strain was detected (0.4%), despite the
      predominance of genotype E (41%). Other frequent genotypes were genotypes D
      (19%), F (13%), G (11 %), and J (7%). Genotype L2b, causing lymphogranuloma
      venereum, was detected in men who have sex with men (MSM) in all three regions.
      Genotypes E and F were more frequent in women and heterosexual men, and genotypes
      D, G, J and L2b in MSM. In men, the main factor causing differences in the
      distribution of C. trachomatis was sexual behavior (MSM versus heterosexual men),
      while the distribution of C. trachomatis genotypes was similar in women and
      heterosexual men.

PMID- 25056130
TI  - Cell-penetrating, dimeric alpha-helical peptides: nanomolar inhibitors of HIV-1
      transcription.
AB  - We constructed dimeric alpha-helical peptide bundles based on leucine (L) and
      lysine (K) residues for both efficient cell penetration and inhibition of the Tat
      TAR interaction. The LK dimers can penetrate nearly quantitatively into
      eukaryotic cells and effectively inhibit the elongation of the TAR transcript at
      low nanomolar concentrations. The effective inhibition of HIV-1 replication
      strongly suggests that the LK dimer has strong potential as an anti-HIV-1 drug. 

PMID- 25056132
TI  - Population study of disease burden, management, and treatment of bipolar disorder
      in Sweden: a retrospective observational registry study.
AB  - OBJECTIVES: The aim of the study was to describe temporal changes in bipolar
      disorder during 20 years within the Swedish population and to investigate
      clinical and socioeconomic characteristics, drug treatment, and mortality among
      patients with bipolar disorder. METHODS: We conducted a retrospective, nationwide
      registry study (the Swedish Population Register) that included all patients
      diagnosed with bipolar disorder (1991-2010) and linked individual data from the
      Swedish National Patient Register, the National Prescribed Drug Register, and the
      Population Register (NCT01455961). A cross-sectional cohort analysis was
      performed for years 2006 versus 2009. Data were analyzed using descriptive
      statistics. RESULTS: During the study period, the annual incidence of diagnosed
      bipolar disorder increased 3.5-fold, and patients were diagnosed at a younger
      age. Mortality among patients with bipolar disorder was twice that of the general
      population. Compared to an age-standardized population, 30% fewer patients with
      bipolar disorder were available for work. Among the 40% employed, 64% reported
      sick leave (46% >100 days/year). Despite similar education levels, disposable
      income was lower compared to the general population. The most commonly preceding
      psychiatric diagnoses were depressive or anxiety disorders. Comparing the data
      for 2006 and 2009 demonstrated similar somatic comorbidity burdens and
      socioeconomic levels. There was also a decrease in dispensed antipsychotic
      medications and lithium, while antiepileptic prescriptions increased slightly.
      Antidepressant dispenses remained virtually unchanged. CONCLUSIONS: In Sweden,
      the incidence and prevalence of diagnosed bipolar disorder have increased during
      the last 20 years. Compared to the general population, these patients had similar
      education levels, lower employment levels, less disposable income, more sick
      leave, and twice the mortality. A trend towards earlier diagnosis, more use of
      antidepressants, and less use of lithium was seen.

PMID- 25056131
TI  - Positive Affect Processing and Joint Attention in Infants at High Risk for
      Autism: An Exploratory Study.
AB  - Few behavioral indices of risk for autism spectrum disorders (ASD) are present
      before 12 months, and potential biomarkers remain largely unexamined. This
      prospective study of infant siblings of children with ASD (n = 16) and low-risk
      comparison infants (n = 15) examined group differences in event-related
      potentials (ERPs) indexing processing of facial positive affect (N290/P400, Nc)
      at 9 months and their relation to joint attention at 15 months. Group differences
      were most pronounced for subtle facial expressions, in that the low-risk group
      exhibited relatively longer processing (P400 latency) and greater attention
      resource allocation (Nc amplitude). Exploratory analyses found associations
      between ERP responses and later joint attention, suggesting that attention to
      positive affect cues may support the development of other social competencies.

PMID- 25056134
TI  - Skin and glucocorticoids: effects of local skin glucocorticoid impairment on skin
      homeostasis.
AB  - The role of skin as a de novo source of glucocorticoids and the importance of
      cutaneous glucocorticoidogenesis as a homeostatic mechanism in human skin is
      highlighted by Slominski et al. in a recently published issue. Impairment of
      glucocorticoidogenesis through noxious stimuli, such as UVB, can explain
      pathophysiology of skin diseases (e.g. rosacea). In addition to keratinocytes,
      melanocytes and fibroblasts, cutaneous adnexes also play a significant role as
      targets and sources of glucocorticoids, because they express most of the enzymes
      required for steroidogenesis. Glucocorticoids are also involved in the
      pathogenesis of acne lesions, affecting sebum production in vivo and in vitro.
      Certain steroidogenic enzymes, such as 11beta-hydroxysteroid dehydrogenase, are
      upregulated in acne lesions. On this background, the paper by Slominski et al.
      provides further insights into dermatoendocrinology, with emphasis on the
      importance of an impairment of the skin's own hypothalamic-pituitary-adrenal-like
      axis in the pathophysiology of several skin diseases. 

PMID- 25056133
TI  - Cytotoxicity of Eupatorium cannabinum L. ethanolic extract against colon cancer
      cells and interactions with Bisphenol A and Doxorubicin.
AB  - BACKGROUND: Eupatorium cannabinum L. has long been utilized in traditional
      medicine, however no information is available regarding cellular effects of full
      extracts. Here we assessed the effects of E. cannabinum ethanolic extract (EcEE)
      on the colon cancer line HT29. Potential interactions with bisphenol A (BPA) a
      synthetic phenolic compound to which humans are generally exposed and a commonly
      used chemotherapeutic agent, doxorubicin (DOX) were also evaluated. METHODS: HT29
      cells were exposed to different concentrations (0.5 to 50 MUg/ml) of EcEE alone
      or in combination with BPA or DOX. Cell viability was analyzed through resazurin
      assay. Gene transcription levels for NCL, FOS, p21, AURKA and bcl-xl were
      determined through qRT-PCR. Cytological analysis included evaluation of nuclear
      and mitotic anomalies after DAPI staining, immunodetection of histone H3 lysine 9
      acetylation (H3K9ac) and assessment of DNA damage by TUNEL assay. RESULTS: Severe
      loss of HT29 cell viability was detected for 50 MUg/ml EcEE immediately after 24
      h exposure whereas the lower concentrations assayed (0.5, 5 and 25 MUg/ml)
      resulted in significant viability decreases after 96 h. Exposure to 25 MUg/ml
      EcEE for 48 h resulted in irreversible cell damage leading to a drastic decrease
      in cell viability after 72 h recovery in EcEE-free medium. 48 h 25 MUg/ml EcEE
      treatment also induced alteration of colony morphology, H3K9 hyperacetylation,
      transcriptional up regulation of p21 and down regulation of NCL, FOS and AURKA,
      indicating reduced proliferation capacity. This treatment also resulted in
      drastic mitotic and nuclear disruption accompanied by up-regulation of bcl-xl,
      limited TUNEL labeling and nuclear size increase, suggestive of a non-apoptocic
      cell death pathway. EcEE/BPA co-exposure increased mitotic anomalies particularly
      for the lowest EcEE concentration, although without major effects on viability.
      Conversely, EcEE/DOX co-exposure decreased cell viability in relation to DOX for
      all EcEE concentrations, without affecting the DOX-induced cell cycle arrest.
      CONCLUSIONS: EcEE has cytotoxic activity on HT29 cancer cells leading to mitotic
      disruption and non-apoptotic cell death without severe induction of DNA damage.
      Interaction experiments showed that EcEE can increase BPA aneugenic effects and
      EcEE synergistic effects with DOX supporting a potential use as adjuvant in
      chemotherapeutic approaches.

PMID- 25056135
TI  - New biomarkers for the prediction of spontaneous preterm labour in symptomatic
      pregnant women: a comparison with fetal fibronectin.
AB  - OBJECTIVE: To identify cervicovaginal fluid (CVF) biomarkers predictive of
      spontaneous preterm birth in women with symptoms of preterm labour. DESIGN:
      Retrospective cohort study. SETTING: Melbourne, Australia. POPULATION: Women with
      a singleton pregnancy admitted to the Emergency Department between 22 and 36
      weeks of gestation presenting with symptoms of preterm labour. METHODS: Two
      dimensional electrophoresis was used to analyse the CVF proteome. Validation of
      putative biomarkers was performed using enzyme-linked immunosorbent assay (ELISA)
      in an independent cohort. Optimal concentration thresholds of putative biomarkers
      were determined and the predictive efficacy for preterm birth was compared with
      that of fetal fibronectin. MAIN OUTCOME MEASURES: Prediction of spontaneous
      preterm labour within 7 days. RESULTS: Differentially expressed proteins were
      identified by proteomic analysis in women presenting with 'threatened' preterm
      labour without cervical change who subsequently delivered preterm (n = 12 women).
      ELISA validation using an independent cohort (n = 129 women) found albumin and
      vitamin D-binding protein (VDBP) to be significantly altered between women who
      subsequently experienced preterm birth and those who delivered at term.
      Prediction of preterm delivery within 7 days using a dual biomarker model
      (albumin/VDBP) provided 66.7% sensitivity, 100% specificity, 100% positive
      predictive value (PPV) and 96.7% negative predictive value (NPV), compared with
      fetal fibronectin yielding 66.7, 87.9, 36.4 and 96.2%, respectively (n = 64).
      Using the maximum number of screened samples, the predictive utility of
      albumin/VDBP yielded a sensitivity of 77.8%, specificity and PPV of 100% and NPV
      of 98.0% (n = 109). CONCLUSIONS: The dual biomarker model of albumin/VDBP is more
      efficacious than fetal fibronectin in predicting spontaneous preterm delivery in
      symptomatic women within 7 days. A clinical diagnostic trial is required to test
      this model on a larger population to confirm these findings and to further refine
      the predictive values.

PMID- 25056136
TI  - Courts issue conflicting decisions on US health exchange subsidies.

PMID- 25056137
TI  - Bilateral failure of cerebral autoregulation is related to unfavorable outcome
      after subarachnoid hemorrhage.
AB  - BACKROUND: The extent of hemodynamic disturbances following subarachnoid
      hemorrhage (SAH) varies. We aim to determine the prognostic implications of
      unilateral and bilateral autoregulatory failure on delayed cerebral ischemia
      (DCI) and outcome. METHODS: Ninety-eight patients with aneurysmal SAH were
      recruited. Autoregulation was assessed using systolic flow index-Sxa.
      Interhemispheric difference in autoregulation was calculated to assess the
      spatial distribution and symmetry of autoregulatory changes. Assessment of
      interhemispheric difference in autoregulation in combination with overall
      autoregulation was used to measure the extent of autoregulatory impairment.
      Patients were dichotomized by the presence of DCI and 3-month mRS. RESULTS:
      Higher flow velocity and worse autoregulation (p < 0.0000001, 95 % CI 10.7-21.3
      and p = 0.00001, 95 % CI 0.03-0.07 for difference in FV and Sxa, respectively)
      were found ipsilateral to the ischemic hemisphere or location of aneurysm (if no
      ischemia detected). DCI group had a higher interhemispheric difference of
      autoregulation than non-DCI group (p = 0.035, 95 % CI 0.003-0.08). 16/18 patients
      with unfavorable outcome vs. 17/72 with favorable outcome had overall poor
      autoregulation with low interhemispheric differences (p = 0.0013, chi (2)).
      Unilateral autoregulatory failure was seen on a median day 3, bilateral on day 4,
      and vasospasm was detected on day 6. CONCLUSIONS: Unilateral autoregulation
      failure was seen in patients who developed DCI (worse ipsilateral to the ischemic
      hemisphere). Bilateral autoregulation failure was seen more frequently in
      patients with unfavorable outcome. Analysis of the temporal profile showed
      unilateral dysautoregulation as the primary event predisposing to DCI, which in
      selected cases led to bilateral failure and unfavorable outcomes.

PMID- 25056138
TI  - Timing and intensity of exercise for glucose control.

PMID- 25056139
TI  - Quality of uncomplicated malaria case management in Ghana among insured and
      uninsured patients.
AB  - INTRODUCTION: The National Health Insurance Act, 2003 (Act 650) established the
      National Health Insurance Scheme (NHIS) in Ghana with the aim of increasing
      access to health care and improving the quality of basic health care services for
      all citizens. The main objective is to assess the effect of health insurance on
      the quality of case management for patients with uncomplicated malaria,
      ascertaining any significant differences in treatment between insured and non
      insured patients. METHOD: A structured questionnaire was used to collect data
      from 523 respondents diagnosed with malaria and prescribed malaria drugs from
      public and private health facilities in 3 districts across Ghana's three
      ecological zones. Collected information included initial examinations performed
      on patients (temperature, weight, age, blood pressure and pulse); observations of
      malaria symptoms by trained staff, laboratory tests conducted and type of drugs
      prescribed. Insurance status of patients, age, gender, education level and
      occupation were asked in the interviews. RESULTS: Of the 523 patients
      interviewed, only 40 (8%) were uninsured. Routine recording of the patients' age,
      weight, and temperature was high in all the facilities. In general, assessments
      needed to identify suspected malaria were low in all the facilities with hot
      body/fever and headache ranking the highest and convulsion ranking the lowest.
      Parasitological assessments in all the facilities were also very low. All
      patients interviewed were prescribed ACTs which is in adherence to the drug of
      choice for malaria treatment in Ghana. However, there were no significant
      differences in the quality of malaria treatment given to the uninsured and
      insured patients. CONCLUSION: Adherence to the standard protocol of malaria
      treatment is low. This is especially the case for parasitological confirmation of
      all suspected malaria patients before treatment with an antimalarial as currently
      recommended for the effective management of malaria in the country. The results
      show that about 16 percent of total sample were parasitologically tested.
      Effective management of the disease demands proper diagnosis and treatment and
      therefore facilities need to be adequately supplied with RDTs or be equipped with
      well functioning laboratories to provide adequate testing.

PMID- 25056140
TI  - Mass treatment with statins.

PMID- 25056141
TI  - Ferroelectric tunnel junctions for information storage and processing.
AB  - Computer memory that is non-volatile and therefore able to retain its information
      even when switched off enables computers that do not need to be booted up. One of
      the technologies for such applications is ferroelectric random access memories,
      where information is stored as ferroelectric polarization. To miniaturize such
      devices to the size of a few nanometres, ferroelectric tunnel junctions have seen
      considerable interest. There, the electric polarization determines the electrical
      resistance of these thin films, switching the current on and off. With control
      over other parameters such as magnetism also being possible, ferroelectric tunnel
      junctions represent a promising and flexible device design. 

PMID- 25056142
TI  - Transmission electron microscopy enables the reconstruction of the catenane and
      ring forms of CS2 hydrolase.
AB  - Transmission electron microscopic studies on CS2 hydrolase provide direct
      evidence for the existence of the hexadecameric catenane and octameric ring
      topologies. Reconstructions of both protein assemblies are in good agreement with
      crystallographic analyses of the catenane and ring forms of CS2 hydrolase. 

PMID- 25056144
TI  - Translational possibility of [18 F]Mefway to image serotonin 1A receptors in
      humans: Comparison with [18 F]FCWAY in rodents.
AB  - PURPOSE: To compare the cerebral uptake and binding potential of [18 F]FCWAY and
      [18 F]Mefway in the rodent to assess their potential for imaging serotonin 1A (5
      HT1A ) receptors. MATERIALS AND METHODS: In vitro liver microsomal studies were
      performed to evaluate the degree of defluorination. Dynamic positron emission
      tomography (PET) studies were then conducted for 2 h with or without an anti
      defluorination agent. The regions of interest were the hippocampus and frontal
      cortex (5-HT1A target regions) and the cerebellum (5-HT1A nontarget region). The
      in vivo kinetics of the radioligands were compared based on the brain uptake
      values and target-to-nontarget ratio. We also performed a comparison of binding
      potential (BPND ) as a steady-state binding parameter. Finally, binding
      affinities to 5-HT1A receptors were assessed in Chinese hamster ovary cells (CHO
      K1) cells expressing human recombinant 5-HT1A receptors. RESULTS: The
      radiochemical yield of [18 F]Mefway was slightly higher than that of [18 F]FCWAY
      (19 vs. 15%). With regard to metabolic stability against defluorination, both
      compounds exhibited similar stability in rat liver microsomes, but [18 F]Mefway
      displayed higher stability in the human microsome (defluorination ratio at 30
      min: 32 vs. 29 in rat liver microsomes, 31 vs. 64 in human liver microsomes for
      [18 F]Mefway and [18 F]FCWAY, respectively). There were no significant
      differences in brain uptake, the target-to-nontarget ratios, and the BPND (at
      hippocampus, peak brain uptakes: 6.9 vs. 8.5, target-to-nontarget ratios: 6.9 vs.
      8.5, BPND : 5.2 vs. 6.2 for [18 F]Mefway and [18 F]FCWAY). The binding affinity
      of [18 F]Mefway was considerably higher than that of [18 F]FCWAY (IC50 : 1.5 nM
      vs. 2.2 nM). CONCLUSION: [18 F]Mefway exhibits favorable characteristics compared
      to [18 F]FCWAY in rodents, and may be a promising radioligand for use in human
      subjects. Synapse 68:595-603, 2014. (c) 2014 Wiley Periodicals, Inc.

PMID- 25056143
TI  - Candidaemia observed at a university hospital in Milan (northern Italy) and
      review of published studies from 2010 to 2014.
AB  - BACKGROUND: Candida species represent the fourth leading cause of nosocomial
      bloodstream infections (BSI) worldwide. However, candidaemia rates and species
      involved vary geographically. OBJECTIVES: To evaluate the epidemiological
      pattern, risk factors for mortality and antifungal therapy of Candida BSI over a
      5-year period (2008-2012) in a university hospital in northern Italy together
      with a review of the recent literature concerning candidaemia. METHODS: A
      retrospective cohort study cross-linked with microbiology database was performed.
      RESULTS: A total of 89 Candida BSI were identified in 42 males (47 %) and 47
      females (52.8 %). The median age was 69 years (interquartile range 55-78) with
      61.8 % of patients being older than 65 years. Considering all hospitalized
      patients, the overall incidence rate of candidaemia increased significantly from
      2008 to 2012 (from 0.4 to 1.68 episodes per 10,000 patient/days) (p = 0.0001)
      with a mean linear increase in 5 new cases per year. Candida albicans was the
      predominant species isolated (64 %) followed by C. glabrata (19.1 %). The latter
      species was observed with significantly higher frequency in Internal Medicine and
      Intensive Care Units (ICU). In-hospital crude mortality was 41.6 %. CONCLUSIONS:
      Candidaemia is an increasing BSI in our university hospital, in accordance with
      that observed in northern Italy, and it is still associated with high in-hospital
      crude mortality.

PMID- 25056145
TI  - A checklist designed to aid consistency and reproducibility of GRADE assessments:
      development and pilot validation.
AB  - BACKGROUND: The grading of recommendation, assessment, development and evaluation
      (GRADE) approach is widely implemented in health technology assessment and
      guideline development organisations throughout the world. GRADE provides a
      transparent approach to reaching judgements about the quality of evidence on the
      effects of a health care intervention, but is complex and therefore challenging
      to apply in a consistent manner. METHODS: We developed a checklist to guide the
      researcher to extract the data required to make a GRADE assessment. We applied
      the checklist to 29 meta-analyses of randomised controlled trials on the
      effectiveness of health care interventions. Two reviewers used the checklist for
      each paper and used these data to rate the quality of evidence for a particular
      outcome. RESULTS: For most (70%) checklist items, there was good agreement
      between reviewers. The main problems were for items relating to indirectness
      where considerable judgement is required. CONCLUSIONS: There was consistent
      agreement between reviewers on most items in the checklist. The use of this
      checklist may be an aid to improving the consistency and reproducibility of GRADE
      assessments, particularly for inexperienced users or in rapid reviews without the
      resources to conduct assessments by two researchers independently.

PMID- 25056146
TI  - A new Division of Ecoimmunology and Disease Ecology.
AB  - The Division of Ecoimmunology and Disease Ecology (hereafter, DEDE) was founded
      in January 2014, and its bylaws approved in May of that year, to encourage the
      growth of research addressing the mechanistic aspects of host-parasite
      interactions. The purpose of DEDE is to facilitate communication, research, and
      data-sharing among scientists and promote mentoring and training of students and
      early career investigators, excellence of research, and the fundamentals of
      societal business. Here, we review briefly the history of the field, and the
      history of the discipline with SICB. 

PMID- 25056147
TI  - A chemical strategy for the cell-based detection of HDAC activity.
AB  - A strategy for activity-based enzyme detection using a novel enamide-based
      chemical strategy is described. Enzymatic cleavage of an amide bond results in
      the formation of an aldehyde. The interaction of this aldehyde with proteins
      increases retention in cells that express the enzyme. Proof of concept for this
      enamide-based strategy is demonstrated by detecting histone deacetylase (HDAC)
      activity in HeLa cells. The modular design of this strategy makes it amenable to
      in vitro and in vivo detection.

PMID- 25056148
TI  - The role of computed tomography in the assessment of dental disease in 66 guinea
      pigs.
AB  - Sixty-six guinea pigs with dental disease were presented to the University of
      Veterinary Medicine, Vienna, Austria, from 2006 to 2010. Almost all patients had
      a history of eating difficulties (95 per cent) and underwent clinical and oral
      examination as well as CT of the head. Findings on extra- and intraoral
      examination were asymmetric elongation (n=28) and symmetric bridging (n=24) of
      cheek teeth, obliquely worn incisors (n=17), palpable lower jaw swellings (n=13),
      exophthalmos (n=10) and incisor macrodontia (n=6). Eighty per cent of guinea pigs
      with exophthalmos showed ipsilateral periapical disease of the maxillary cheek
      teeth on CT. Ninety-two per cent of patients with palpable lower jaw swellings
      showed corresponding dental pathologies on CT. Periapical disease of incisors
      (n=11) and cheek teeth (n=32) were the most common findings on CT. All abnormally
      large incisors were found on oral examination and CT, but macrodontia of cheek
      teeth could only be visualised by CT. Deviation of the lower jaw evaluated in
      awake animals by visual inspection appeared to correlate with cheek teeth
      abnormalities. Results emphasise the importance of diagnostic imaging, in
      particular CT, in guinea pigs with dental disease in order to localise lesions
      and underlying aetiologies.

PMID- 25056150
TI  - What medical students need: Virtual patients or real patients?

PMID- 25056149
TI  - East-West differences in perception of brain death. Review of history, current
      understandings, and directions for future research.
AB  - The concept of brain death as equivalent to cardiopulmonary death was initially
      conceived following developments in neuroscience, critical care, and transplant
      technology. It is now a routine part of medicine in Western countries, including
      the United States. In contrast, Eastern countries have been reluctant to
      incorporate brain death into legislation and medical practice. Several countries,
      most notably China, still lack laws recognizing brain death and national medical
      standards for making the diagnosis. The perception is that Asians are less likely
      to approve of brain death or organ transplant from brain dead donors. Cultural
      and religious traditions have been referenced to explain this apparent
      difference. In the West, the status of the brain as home to the soul in
      Enlightenment philosophy, combined with pragmatism and utilitarianism, supports
      the concept of brain death. In the East, the integration of body with spirit and
      nature in Buddhist and folk beliefs, along with the Confucian social structure
      that builds upon interpersonal relationships, argues against brain death.
      However, it is unclear whether these reasoning strategies are explicitly used
      when families and medical providers are faced with acknowledging brain death.
      Their decisions are more likely to involve a prioritization of values and a
      rationalization of intuitive responses. Why and whether there might be
      differences between East and West in the acceptance of the brain death concept
      requires further empirical testing, which would help inform policy-making and
      facilitate communication between providers and patients from different cultural
      and ethnic backgrounds. 

PMID- 25056151
TI  - Physical therapy treatment in patients suffering from cervicogenic somatic
      tinnitus: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Tinnitus occurs in a large part of the general population with
      prevalences ranging from 10% to 15% in an adult population. One subtype is
      cervicogenic somatic tinnitus, arising from cervical spine dysfunctions,
      justifying cervical spine assessment and treatment. This study aims to
      investigate the effect of a standardized physical therapy treatment, directed to
      the cervical spine, on tinnitus. Additionally, a second aim is to identify a
      subgroup within the tinnitus population that benefits from physical therapy
      treatment. METHODS AND DESIGN: This study is designed as a randomized controlled
      trial with delayed treatment design. Patients with severe subjective tinnitus
      (Tinnitus Functional Index (TFI) between 25 and 90 points), in combination with
      neck complaints (Neck Bournemouth Questionnaire (NBQ) >14 points) will be
      recruited from the University Hospital of Antwerp. Patients suffering from
      tinnitus with clear otological etiologies, severe depression, traumatic cervical
      spine injury, tumors, cervical spine surgery, or conditions in which physical
      therapy is contra-indicated, will be excluded.After screening for eligibility,
      baseline data such as TFI, NBQ, and a set of cervical biomechanical and
      sensorimotor tests will be collected. Patients are randomized in an immediate
      therapy group and in a group with a delayed start of therapy by 6 weeks. Patients
      will receive physical therapy with a maximum of 12 sessions of 30 min for a 6
      week program. Data from the TFI and NBQ will be collected at baseline (week 0),
      at the start of therapy (weeks 0 or 6), at the end of therapy (weeks 6 or 12), 6
      weeks after therapy (weeks 12 or 18), and 3 months after therapy (weeks 18 or
      24). Secondary outcome measures will be collected at baseline and 6 weeks after
      the therapy (weeks 12 or 18), as the maximal therapy effect on the cervical spine
      dysfunctions is expected at that moment. DISCUSSION: This study is the first to
      investigate the effect of a standardized physical therapy treatment protocol on
      somatic tinnitus with a prospective comparative delayed design and with blinded
      evaluator for baseline, end of therapy, and 6 and 12 weeks after therapy. TRIAL
      REGISTRATION: 12 September 2013, ClinicalTrials.gov: NCT02016313.

PMID- 25056154
TI  - Sulfur gradient-distributed CNF composite: a self-inhibiting cathode for binder
      free lithium-sulfur batteries.
AB  - A self-inhibiting, gradient sulfur structure was designed and developed by the
      synthesis of a carbon nanofiber-sulphur composite via sulfur vapor deposition
      method for use as a binder-free sulfur cathode, exhibiting high sulfur loading
      (2.6 mg cm(-2)) and high sulfur content (65%) with a stable capacity of >700 mA h
      g(-1). 

PMID- 25056156
TI  - Ten-year advances in immunopathology of glomerulonephritis: translated into
      patients' care or lost in translation?

PMID- 25056155
TI  - The immunopathology of ANCA-associated vasculitis.
AB  - The small-vessel vasculitides are a group of disorders characterised by variable
      patterns of small blood vessel inflammation producing a markedly heterogeneous
      clinical phenotype. While any vessel in any organ may be involved, distinct but
      often overlapping sets of clinical features have allowed the description of three
      subtypes associated with the presence of circulating anti-neutrophil cytoplasmic
      antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known
      as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic
      granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss
      syndrome). Together, these conditions are called the ANCA-associated
      vasculitidies (AAV). Both formal nomenclature and classification criteria for the
      syndromes have changed repeatedly since their description over 100 years ago and
      may conceivably do so again following recent reports showing distinct genetic
      associations of patients with detectable ANCA of distinct specificities. ANCA are
      not only useful in classifying the syndromes but substantial evidence implicates
      them in driving disease pathogenesis although the mechanism by which they develop
      and tolerance is broken remains controversial. Advances in our understanding of
      the pathogenesis of the syndromes have been accompanied by some progress in
      treatment, although much remains to be done to improve the chronic morbidity
      associated with the immunosuppression required for disease control. 

PMID- 25056157
TI  - CHI3L1 polymorphisms associate with asthma in a Taiwanese population.
AB  - BACKGROUND: A genome-wide association study uncovered Chitinase 3 like 1 (CHI3L1)
      as a candidate gene for asthma susceptibility. CHI3L1, which encodes the YKL-40
      protein, is associated with asthma in Western European and American populations
      and with atopy in a Korean population. However, asthma-associated polymorphisms
      remain unknown for a Taiwanese population. METHODS: We enrolled 628 adult
      asthmatic patients and 1:1 age-sex matched community-based controls in southern
      Taiwan and performed a combined effect sizes analysis to test if CHI3L1
      polymorphisms were related to genetic risks for asthma in the Asian population.
      Ten tagSNP polymorphisms for the CHI3L1 gene were selected from the HapMap
      database and genotyped using a TaqMan allelic discrimination assay. RESULTS:
      Adjusted odds ratios of the CHI3L1 rs1538372 CC genotype (aOR = 1.97, 95% CI:
      1.23-3.14) and the rs10399931 GG genotype (aOR = 1.77, 95% CI: 1.13-2.77) were
      significantly associated with asthma in the Taiwanese populations. Predictive
      values of forced expiratory volume in the first second of the forced vital
      capacity (12.37%, P = 0.03) and of forced vital capacity (12.10%, P = 0.036)
      decreased in conjunction with an increase in YKL-40 levels among CHI3L1 rs1538372
      CC carriers; these values were 16.1% (P = 0.004) and 14.5% (P = 0.011),
      respectively, among CHI3L1 rs10399931 GG carriers. Furthermore, steroid use by
      asthma patients did not affect serum YKL-40 levels, but both polymorphisms had
      significant effects on YKL-40 levels in asthma patients who used steroids.
      CONCLUSIONS: Our findings suggest that the CHI3L1 polymorphisms rs1538372 and
      rs10399931 can be used as genetic markers for predicting asthma risk in the
      Taiwanese population.

PMID- 25056158
TI  - Short-term heart rate variability in a population-based sample of 10-year-old
      children.
AB  - Heart rate variability (HRV) is a non-invasive quantitative marker of cardiac
      autonomic function derived from continuous electrocardiogram (ECG) recordings.
      Normative HRV values and development factors have not been established in
      pediatric populations. The objective was to derive referent time- and frequency
      domain HRV values for a population-based sample of children. Children aged 9-11
      years (N = 1,036) participated in the Quebec Longitudinal Study of Child
      Development cohort cardiovascular health screening. Registered nurses measured
      anthropometrics (height, weight) and children wore an ambulatory Holter monitor
      to continuously record an ECG signal. HRV variables included time (SDNN, pNN50,
      RMSSD, SDANN) and frequency (HF, LF, LF/HF ratio) domain variables. Normative HRV
      values, stratified by age, sex, and heart rate, are presented. Greater heart rate
      (beta avg  = -0.60, R avg (2)  = 0.39), pubertal maturation (beta avg = -0.11, R
      avg (2)  = 0.01), later ECG recording times (beta avg = -0.19, R avg (2)  =
      0.07), and higher diastolic blood pressure (beta avg = -0.11, R avg (2)  = 0.01)
      were significantly associated with reduced HRV in 10-year-old children. The
      normative HRV values permit clinicians to monitor, describe, and establish
      pediatric nosologies in primary care and research settings, which may improve
      treatment of diseases associated with HRV in children. By better understanding
      existing values, the practical applicability of HRV among clinicians will be
      enhanced. Lastly, developmental (e.g., puberty) and procedural (e.g., recording
      time) factors were identified that will improve recording procedures and
      interpretation of results. 

PMID- 25056160
TI  - Annual variation of dietary deoxynivalenol exposure during years of different
      Fusarium prevalence: a pilot biomonitoring study.
AB  - Dietary exposure to deoxynivalenol (DON) has been reported previously in the UK,
      but levels were low and most individuals are well protected by the maximum
      permitted levels in food set by the European Commission. However, no information
      is available on annual fluctuation in dietary DON exposure. We hypothesised that
      dietary DON exposure may vary when individuals consume cereals derived from
      harvests with low (2011) and high (2012) Fusarium prevalence. In this pilot
      study, spot urine samples were collected in years 1 and 2 from 15 volunteers
      following their habitual diet. Urinary DON was analysed by LC-MS/MS to estimate
      24-h DON excretion and daily dietary DON intake. DON was detectable in all urine
      samples with an average excretion of 10.08 +/- 9.13 ug/24-h urine in year 1 which
      significantly (p = 0.005) increased to 24.84 +/- 13.83 ug/24-h urine in year 2.
      This resulted from an estimated dietary intake of 195.94 +/- 166.44 ng DON kg(-1)
      BW in year 1 and 518.64 +/- 292.49 ng DON kg(-1) BW in year 2. Based on these
      estimates, the tolerable daily intake for DON was exceeded in 13% of occasions in
      year 2 and none in year 1. This pilot study is based on estimates of DON intake
      derived from urinary DON excretion. Results suggest that DON exposure varies
      annually and that current maximum levels might not sufficiently protect consumers
      during years of high Fusarium prevalence.

PMID- 25056159
TI  - LTR retroelements are intrinsic components of transcriptional networks in frogs.
AB  - BACKGROUND: LTR retroelements (LTR REs) constitute a major group of transposable
      elements widely distributed in eukaryotic genomes. Through their own mechanism of
      retrotranscription LTR REs enrich the genomic landscape by providing genetic
      variability, thus contributing to genome structure and organization. Nonetheless,
      transcriptomic activity of LTR REs still remains an obscure domain within cell,
      developmental, and organism biology. RESULTS: Here we present a first comparative
      analysis of LTR REs for anuran amphibians based on a full depth coverage
      transcriptome of the European pool frog, Pelophylax lessonae, the genome of the
      African clawed frog, Silurana tropicalis (release v7.1), and additional
      transcriptomes of S. tropicalis and Cyclorana alboguttata. We identified over
      1000 copies of LTR REs from all four families (Bel/Pao, Ty1/Copia, Ty3/Gypsy,
      Retroviridae) in the genome of S. tropicalis and discovered transcripts of
      several of these elements in all RNA-seq datasets analyzed. Elements of the
      Ty3/Gypsy family were most active, especially Amn-san elements, which accounted
      for approximately 0.27% of the genome in Silurana. Some elements exhibited tissue
      specific expression patterns, for example Hydra1.1 and MuERV-like elements in
      Pelophylax. In S. tropicalis considerable transcription of LTR REs was observed
      during embryogenesis as soon as the embryonic genome became activated, i.e. at
      midblastula transition. In the course of embryonic development the spectrum of
      transcribed LTR REs changed; during gastrulation and neurulation MuERV-like and
      SnRV like retroviruses were abundantly transcribed while during organogenesis
      transcripts of the XEN1 retroviruses became much more active. CONCLUSIONS: The
      differential expression of LTR REs during embryogenesis in concert with their
      tissue-specificity and the protein domains they encode are evidence for the
      functional roles these elements play as integrative parts of complex regulatory
      networks. Our results support the meanwhile widely accepted concept that
      retroelements are not simple "junk DNA" or "harmful genomic parasites" but
      essential components of the transcriptomic machinery in vertebrates.

PMID- 25056161
TI  - Dabigatran, rivaroxaban and apixaban for extended venous thromboembolism
      treatment: network meta-analysis.
AB  - AIM: Many new oral anticoagulants (NOACs; dabigatran, rivaroxaban, and apixaban)
      are currently available to treat thromboembolic disease. There are no head-to
      head trials comparing these agents. To assess the efficacy and safety of NOACs
      for prevention of recurrent venous thromboembolism (VTE), we performed a network
      meta-analysis. METHODS: Medline, Embase, and the Cochrane-controlled trial
      register were searched, without language restriction, to identify trials. Studies
      were evaluated according to a priori inclusion criteria and appraised using
      established internal validity criteria. Adjusted indirect comparisons between
      agents were performed using well-established methods. RESULTS: Three trials
      meeting inclusion criteria were identified. Direct comparison between apixaban
      2.5 mg twice daily (BID) versus apixaban 5 mg BID showed no difference for any
      outcome. Clinically relevant non-major bleeding occurred less with both apixaban
      2.5 mg BID (OR 0.23, 95% CI 0.08-0.62, P=0.004) and apixaban 5 mg BID [OR 0.31,
      95% CI 0.11-0.82, P=0.019] compared to rivaroxaban 20 mg daily. Apixaban 2.5 mg
      BID showed less clinically relevant non-major bleeding than dabigatran 150 mg BID
      [OR 0.4, 95% CI 0.16-0.9, P=0.04], but not apixaban 5 mg BID. There were no
      differences between rivaroxaban 20 mg daily and dabigatran 150 mg BID. No
      differences in risk for recurrent VTE, major bleeding, or mortality were observed
      for any comparison between any pair of NOACs. CONCLUSION: There were no
      significant differences in risk for recurrent VTE, major bleeding, or all-cause
      mortality between the NOACs. However, apixaban 2.5 mg BID was associated with
      less clinically significant non-major bleeding than either rivaroxaban 20 mg
      daily or dabigatran 150 mg BID.

PMID- 25056162
TI  - The influence of carotid endarterectomy on cerebral blood flow in significant
      carotid stenosis-perfusion computed tomography study.
AB  - AIM: Carotid endarterectomy (CEA) is well recognized procedure in the treatment
      of patients with significant symptomatic internal carotid artery (ICA) stenosis.
      Operation reconstitutes physiologic blood flow in the ICA. The influence of CEA
      on cerebral perfusion (CP) is not well established. Some data suggest increased
      CP after stenosis correction however evidence in post-endarterectomy patients is
      scarce. Our aim was to investigate the influence of CEA in patients with
      symptomatic carotid stenosis on CP parameters by means of perfusion computed
      tomography (PCT). METHODS: Thirty-four patients with symptomatic severe carotid
      stenosis qualified for CEA were included. The baseline PCT of the brain according
      to standardized protocol was performed within 3 weeks prior to surgical
      procedure. The follow-up PCT was performed between 30-60th day postop. The
      following perfusion parameters were analyzed: cerebral blood flow (CBF), cerebral
      blood volume (CBV), peak enhancement intensity (PEI) and time to peak (TTP). Pre-
      and postoperative average values of these parameters were compared. RESULTS: No
      death/stroke occurred in the investigated group. Mean preoperative total CBF was
      66.2 mL/100 g/min and was not dependent on the degree of the carotid stenosis or
      the presence of contralateral carotid artery stenosis. Mean postoperative total
      CBF was significantly lower (61.8 mL/100g/min, P<0.05). No significant changes in
      PEI, TTP and CBV were observed CONCLUSION: PCT of the brain reveals that CEA in
      patients with symptomatic carotid stenosis decreased total CBF especially in the
      contralateral hemisphere.

PMID- 25056163
TI  - Association of serum homocysteine levels with the severity and calcification of
      coronary atherosclerotic plaques detected by coronary CT angiography.
AB  - AIM: In this study, we aim to evaluate the association of risk factors including
      homocysteine (Hcy) with the severity and burden of coronary atherosclerotic
      plaques detected by computed tomography angiography (CTA). METHODS: Six hundred
      fifty-nine subjects who underwent CTA for the assessment of coronary artery
      disease (CAD) were studied. All the subjects enrolled had no clinical
      cardiovascular disease symptoms. Logistic regression showed apart from age,
      hypertension, smoking, triglyceride, low-density lipoprotein (LDL) cholesterol,
      and total bilirubin, Hcy was an independently risk factor of the severity of
      coronary disease. And Hcy was also found an independent predictor for the
      presence of calcified plaque. When the participants were divided into 4 groups
      according to serum Hcy quartiles (Q1-Q4 groups), both the percentage of patients
      with >50% stenosis and the percentage of patients with calcified plaque were
      higher in Q4 compared to other groups. The OR of Hcy (>15 umol/L) for >50%
      stenosis was 2.212 (95% CI=1.119 to 4.375, P=0.022) and the OR for Hcy (>15
      umol/L) for calcification was 1.668 (95% CI=1.030 to 2.699, P=0.037)
      respectively. CONCLUSION: Our study shows Hcy is independently associated with
      both the severity and calcified plaque detected by CTA. Hcy may provide
      additional information about CAD in the subjects without clinical symptoms.

PMID- 25056164
TI  - Risk factors of venous thrombosis in patients with ankle fractures.
AB  - AIM: Deep vein thrombosis (DVT) is a major complication that can occur after
      injuries. our aim was to explore the incidence and risk factors of venous
      thromboembolism in patients with ankle fractures. METHODS: Consecutive patients
      with an isolated fracture of the ankle presenting at our centre between Sept 2004
      and May 2012 were studied. They were investigated for venous thrombosis by
      Doppler sonography (DUS) before surgery. Univariate and multivariate logistic
      regressions analyses were performed to identify the incidence and risk factors
      for venous thromboembolism. RESULTS: A total of 2347 patients were studied in the
      research. Of these, only 119 patients suffered from DVT. The multivariable
      analyses showed that diabetes, less activity and the time from injury were the
      key risk factors for thrombosis. CONCLUSION: In patients with ankle fracture, the
      risk of thrombosis was low and it may not need warrant routine
      thromboprophylaxis. However, most cases had no significant symptoms, is necessary
      to grasp the indications for high risk patients to reduce the incidence rate of
      venous thrombosis.

PMID- 25056165
TI  - Consensus Document on Intermittent Claudication from the Central European
      Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the
      Mediterranean League of Angiology and Vascular Surgery, and the North Africa and
      Middle East Chapter of International Union of Angiology.
AB  - This paper is the review of the Consensus Document on Intermittent Claudication
      of the Central European Vascular Forum (CEVF), published in 2008, and and shared
      with the North Africa and Middle East Chapter of International Union of Angiology
      and the Mediterranean League of Angiology and Vascular Surgery. The Document
      presents suggestions for general practitioners and vascular specialists for more
      precise and appropriate management of PAD, particularly of intermittent
      claudication, and underlines the investigations that should be required by GPs
      and what the GP should expect from the vascular specialist (angiologist, vascular
      surgeon). The idea of the Faculty is to produce a short document, which is an
      easy reference in daily clinical practice, both for the GPs and vascular
      specialists. 

PMID- 25056166
TI  - Comparison of passive and active biomechanical properties of human cervical and
      leg veins.
AB  - AIM: The aim of this study was to evaluate and compare passive and active
      biomechanical properties of human superficial veins exposed in vivo to different
      orthostatic stresses. METHODS: Superficial veins from jugular and saphenous
      regions were studied (11 segments each). Digitalized pressure-diameter curves
      were recorded in Krebs-Ringer solution, and after administration of 10-5M
      norepinephrine and 10-5M acetylcholine. Calcium-free solution was used to
      determine passive biomechanical properties. Similar tissue samples were collected
      for histochemistry. Resorcin-fuchsin stainings and immuno-histochemistry for
      smooth muscle actin were used. RESULTS: The outer radius of the relaxed samples
      was identical. Leg vein walls were thicker in Krebs-Ringer solution (110 +/- 11
      vs. 84 +/- 7 um at 30 mmHg). Isobaric wall stress was significantly higher in
      cervical veins. The significant differences in incremental distensibilities and
      elastic moduli were dependent on pressure level and smooth muscle tone.
      Spontaneous tone and norepinephrine induced contractions were significantly
      higher in leg veins (at 30 mmHg 18.3 +/- 4.1 vs. 5.6 +/- 1.8% and 37.6 +/- 4.5
      vs. 11.2 +/- 4.3 %, respectively). Endothelial dilation was larger in cervical
      vein segments (3.8 +/- 0.9% vs. 1.8 +/- 0.5%). Resorcin-fuchsin and smooth muscle
      actin staining structures were more abundant in leg veins. CONCLUSION: Comparing
      active and passive biomechanical properties of human veins affected chronically
      by different orthostatic loading, we found several quantitative differences that
      reflect the physiological adaptation mechanisms to long-term gravitational
      stress.

PMID- 25056167
TI  - Acceptance, compliance and effects of compression stockings on venous functional
      symptoms and quality of life of Italian pregnant women.
AB  - AIM: The rates of pregnant women with functional symptoms of venous insufficiency
      who accepted or refused to wear therapeutic compression stockings were evaluated
      and compared in relation to their clinical evolution and their compliance levels.
      METHODS: The observational study was conducted in pregnant women between 4 and 28
      weeks of amenorrhea presenting a CEAP C0S to C3S venous disease. Therapeutic
      compression stockings (BSN medical, UltraSheer Maternity stockings, 15-20 mmHg)
      were offered to pregnant women satisfying the inclusion criteria during routine
      check visits, and both groups of patients (those who accepted as well as those
      who refused) were followed up until the end of the pregnancy. The clinical
      profiles of both groups and the evolution of the venous insufficiency were
      monitored and compared. The women were requested to indicate pain and further
      quality of life parameter by means of a specific questionnaire (CIVIQ). RESULTS:
      Ninety-eight women were included in the study and followed up; 30.6% (N.=30) of
      the women refused to wear compression stockings (Wr), 69.4% accepted 10.6% were
      not compliant to a daily wear (Wanc) and 58.8% wore them every day (Wac). Leg
      pain was more prominent in case of the Wac group (49.5 +/- 21.3) than in case of
      the Wanc (42.1 +/- 20.4) and Wr groups (36.6 +/- 18). Their global quality also
      decreased (48.8 +/- 15.7 vs. 43.6 +/- 16.1 and 36.6 +/- 15.6). Regular use of
      compression stockings led to decrease of pain (Wac -17 +/- 10.1 vs. Wanc -10.3 +/
      10.5 vs. Wr -4.2 +/- 9.8 [P < 0.0001]) and enhanced total quality of life (Wac
      13.5 +/- 9.6 vs. Wanc 10.7 +/- 11.3 vs. Wr -3.3 +/- 9.4 [P < 0.0001). Similar
      results were observed on the CIVIQ subscale (pain, psychological, social,
      physical impact of legs' pain on women quality of life). CONCLUSION: In daily
      practice, more than two third of the pregnant women accepted to wear compression
      stockings. The use of compression stockings reduced the legs pain and increased
      the quality of life of pregnant women.

PMID- 25056168
TI  - The value of extended preoperative thromboprophylaxis with dalteparin in patients
      with ovarian cancer qualified to surgical treatment.
AB  - AIM: Ovarian cancer (OC) is associated with a high risk of venous thromboembolism
      (VTE) in both, pre- and postoperative period. The aim of the study was to analyse
      the efficacy and the safety of an early prophylaxis with dalteparin in patients
      with OC qualified to surgery. METHODS: The prospective, non-randomized study was
      performed in the group of OC patients qualified to surgical treatment. The study
      group (SG) consisted of 37 patients with OC in whom thromboprophylaxis was
      started at the moment of qualification to the surgery (mean 16,1 days +/- 11,32
      SD before procedure). The control group (CG) consisted of 61 patients with OC
      qualified to surgery in whom thromboprophylaxis was started 12 hour before
      surgical treatment. The duration of postoperative prophylaxis was 4 weeks in both
      groups. Dalteparin 5000 U/day was used in both groups. The primary end points
      were occurrence of VTE and major bleeding. The patients underwent color Doppler
      US and D-dimer (DD) assessment at the moment of qualification for surgery, 1 day
      before and 7, 14, 28 days and 3 months after procedure. RESULTS: The total
      duration of thromboprophylaxis was 45.3 +/- 10.7 days in SG and 27.9 +/- 3.7 days
      in CG (P < 0.0001). The deep venous thrombosis rate was 2,7% in SG and 16.4% in
      CG (P = 0.042). Neither pulmonary embolism, nor major bleeding were observed.
      Median preoperative DD concentration in all patients was 1700 ng/ml and was
      significantly higher in patients who developed postoperative DVT when compared to
      those who did not, 2556.8 and 1691.0 ng/mL respectively (P = 0.0009). CONCLUSION:
      Prolonged preoperative thromboprophylaxis with dalteparin in patients with
      ovarian cancer qualified to the surgical treatment is safe, decreases the risk of
      thromboembolic complications. To determine indication, dosage and timing of such
      thromboprophylaxis in this group of patients further studies are required.

PMID- 25056169
TI  - Serum levels for midkine, a heparin-binding growth factor, inversely correlate
      with angiotensin and endothelin receptor autoantibody titers in patients with
      macroangiopathy.
AB  - AIM: Peripheral artery disease results in impaired blood flow to the extremities,
      most often as a consequence of atherosclerotic disease. The hallmark of
      atherosclerosis is chronic inflammation in the vessel wall. The renin-angiotensin
      and endothelin systems are considered important pathophysiological effectors.
      Midkine, a multifunctional cytokine, fulfils different roles in inflammation and
      promotion of neoangiogenesis. The aim of this study was to assess whether
      circulating midkine serum levels in patients with peripheral artery disease
      correlate with established atherosclerosis risk factors, as well as titers of
      functional autoantibodies directed against receptors of the renin-angiotensin and
      endothelin system. METHODS: Clinical data, laboratory values and serum samples
      from 118 patients operated on for severe peripheral artery disease, and from 100
      healthy blood donors were collected. Serum samples were analysed for midkine
      concentrations as well as autoantibody titers against angiotensin II type 1 and
      endothelin-1 type A receptors. RESULTS: Midkine values were significantly higher
      in the study population than in healthy controls (P<0.001). Circulating midkine
      levels did not correlate with neither of the traditional risk factors age, sex,
      obesity, smoking, hypertension, high cholesterol levels, or diabetes mellitus. An
      unexpected inverse correlation was found with the autoantibodies against
      angiotensin II type 1 receptor (P<0.05) and endothelin-1 type A receptor
      (P<0.01). CONCLUSION: The high levels of midkine in severe peripheral artery
      disease patients introduce this cytokine as a possible novel effector in the
      advanced atherosclerotic process. These results also suggest a functional link
      between vascular receptor autoantibody formation and down-regulated midkine serum
      levels, that may be relevant in the pathogenesis of clinically relevant
      peripheral artery occlusive disease.

PMID- 25056170
TI  - Comparison of reported symptoms to those produced by treadmill testing in
      patients with claudication suspected of arterial origin.
AB  - AIM: We aimed at comparing lower limb symptoms reported by history to those
      observed during a standard treadmill test. METHODS: We retrospectively studied
      symptomatic patients referred over a three years period for suspected arterial
      claudication and used the Edinburgh claudication questionnaire before exercise
      and symptoms observed on a treadmill. We confronted, right and left, proximal
      (lower-back thigh or buttocks) and distal (leg or foot) lower-limb symptoms
      before and during treadmill exercise. Results are reported as mean +/- standard
      deviation for percentage and 95% confidence interval and Kappa statistics are
      performed. RESULTS: Of 795 patients with claudication, aged 63 +/- 12 years,
      treadmill test resulted in 715 reporting lower-limb symptoms on treadmill.
      Cohen's Kappa for the site-specific analysis of symptoms by history vs. symptoms
      on treadmill was 0.509 +/- 0.21 (P < 0.01), showing a moderate agreement.
      Nevertheless, symptoms on treadmill reproduced, at least partly, symptoms by
      history in 675 (84.9% 95CI: 82.3-87.2) of patients, although symptoms on
      treadmill were strictly of the same localizations as symptoms by history in only
      378 (47.6% 95CI: 44.1-51.0) of all studied patients. Last, 279 patients (35.1% of
      all patients) reported non limb symptoms on treadmill. CONCLUSION: Although on a
      site by site basis the concordance of symptoms by history to symptoms by
      treadmill is moderate, most patients reproduced their usual symptoms on
      treadmill. Age does not seem to impair the concordance. Last, beyond the sole
      measurement of maximal walking capacity, treadmill frequently unmasks non-limb
      limiting symptoms that may require clinical attention.

PMID- 25056171
TI  - Endovascular repair of postoperative vascular graft related complications after
      aorto-iliac surgery.
AB  - AIM: Para-anastomotic aneurysms, leakage due to anastomotic failure, aorto- and
      arterioenteric fistulas are some of the serious complications after aorto-iliac
      surgical reconstructions. Treatment of these complications is challenging and is
      either done by open surgery or by endovascular therapy. The mortality and
      morbidity is higher compared to the initial treatment. We present twelve patients
      with these complications which were treated by an endovascular approach. METHODS:
      From January 2008 through January 2013 our radiological records were searched for
      cases with post surgical vascular complications treated with endovascular
      intervention. These comprised of anastomotic pseudoaneurysm, suture leakage and
      arterial enteric fistulas. Patients with limb occlusions were not included in
      this study. RESULTS: Twelve patients with graft related complications treated
      with endovascular intervention were recorded. There were four women and eight men
      with a mean age 75,3 years (range 48-80). At the time of diagnosis, 9 patients
      (75%) had symptoms and three (25%) was incidentally discovered. Six patients had
      leakage due to suture failure. All infective parameters were within normal
      limits. Four patients presented with anastomotic pseudoaneurysms without leak, of
      which three had proximal anastomotic pseudoaneurysms and one had distal iliac
      anastomotic pseudoaneurysm. Implanted stent graft were Endurant (Medtronic)
      bifurcated endoprostheses in three patients and Excluder (Gore) prosthesis in a
      two cases. Tubular Medtronic endoprosthesis was implanted in one case and in two
      cases aortic cuff was used. Fluency periphery stent grafts were used in four
      cases. There was a 100% technical success. Intervention related early mortality
      was 8%. One patient with pseudoaneurysm died 28 months after endovascular
      treatment because of cardiac infarct and one patient with previously infected
      arterio-enteric fistula and advanced malignancy died 7 months after second
      endovascular treatment. Overall the mortality was 25%. There was no procedure
      related morbidity or complications during hospitalization and follow-up of mean
      12, 3 months (range 1-36 months) in the other 9 patients. There were no
      complications like endoleaks or limb occlusions. CONCLUSION: Endovascular
      treatment of vascular graft related postsurgical complications is a valuable
      therapeutic option followed by lower mortality and morbidity rates compared with
      re-operation. Short and midterm follow-up is without severe complications and if
      it occurs most of them can be treated by endovascular means again.

PMID- 25056172
TI  - Link between automated coronary calcium volumes from intravascular ultrasound to
      automated carotid IMT from B-mode ultrasound in coronary artery disease
      population.
AB  - AIM: Establishing relationship between coronary calcium volumes from
      Intravascular Ultrasound (IVUS) and automated carotid intima-media thickness
      (cIMT) helps in understanding the genetic nature of atherosclerosis disease. In
      this research, we have quantified the detected calcium from IVUS video frames and
      associated a relationship between coronary calcium volumes computed and automated
      cIMT from B-mode ultrasound. METHODS: Coronary calcium volume is computed from
      IVUS and auto cIMTs are computed using B-mode ultrasound. An automated computer
      based application is developed and tested on 100 patient volumes (an average of
      2549 frames per volume) to calculate lesion area and normalized coronary calcium
      volume. We use an integrated approach for volume computation which is based on
      lesion area per frame. We have measured the normalized volume from the calcium
      detected video frames using proposed integration method. The cIMT of 100 carotids
      were measured with novel and dedicated automated software analysis (AtheroEdgeTM
      from AtheroPointTM LLC, Roseville, CA, USA). RESULTS: The computer-based coronary
      calcium volume (from IVUS) showed a correlation coefficient with respect to cIMT
      for left and right carotids as 9.1% and 13.9%, respectively. CONCLUSION: Coronary
      calcium volume computed from IVUS and auto cIMT are moderately correlated. The
      association between auto cIMT (right side) vs. computer-based coronary calcium
      volume (IVUS) is stronger than the association between auto cIMT (left side) vs.
      computer-based coronary calcium volume.

PMID- 25056173
TI  - Do heterozygous factor V Leiden and prothrombin G20210A mutations have different
      impact on the type and location of venous thromboembolism?

PMID- 25056174
TI  - Commentary: finding the middle bowl: goldilocks' lessons on professional
      competencies in pediatric psychology.

PMID- 25056175
TI  - Near-infrared spectroscopic study of frontopolar activation during face-to-face
      conversation in major depressive disorder and bipolar disorder.
AB  - Major depressive disorder (MDD) and bipolar disorder (BD) patients show speech
      characteristics that vary greatly according to mood state. In a previous study,
      we found impaired temporal and right inferior frontal gyrus (IFG) activation in
      schizophrenia during face-to-face conversation; no study had, however, previously
      investigated mood disorders during face-to-face conversation. Here, we
      investigated frontal and temporal lobe activation during conversation in patients
      with MDD and BD. Frontal and temporal lobe activation was measured using near
      infrared spectroscopy (NIRS) in 29 patients with MDD, 31 patients with BD, and 31
      normal controls (NC). We compared continuous activation and rapid change of
      activation with talk/listen phase changes during the conversation and analyzed
      the correlation between these indices and clinical variables. Both the MDD and BD
      groups showed decreased continuous activation in the left dorsolateral prefrontal
      (DLPFC) and left frontopolar cortices (FPCs); they also showed decreased rapid
      change in bilateral FPC activation. In the MDD group, the rapid change of
      activation was positively correlated with Global Assessment of Functioning (GAF)
      scores. In the BD group, continuous activation was negatively correlated with age
      of onset. These results indicate that frontal activation during conversation
      decreases in both MDD and BD. However, both continuous activation and rapid
      change may reflect the pathophysiological character of MDD and BD; in particular,
      the reduced amount of rapid change in the right FPC may be related to impaired
      adaptive ability in MDD. 

PMID- 25056176
TI  - Muscle and bone effects of androgen deprivation therapy: current and emerging
      therapies.
AB  - Prostate cancer and treatment with androgen deprivation therapy (ADT) affect
      significant numbers of the male population. Endocrine effects of ADT are a
      critical consideration in balancing the benefits and risks of treatment on long
      term survival and quality of life. This review highlights the latest advances in
      androgen manipulation in prostate cancer with an emphasis on the effects of ADT
      on muscle and bone, which universally affects the health and well-being of men
      undergoing ADT for prostate cancer. Muscle mass declines with ADT; however, the
      evidence that this correlates with a decrease in muscle strength or a decrease in
      physical performance is discordant. Cortical bone decay also occurs in
      association with an increase in fracture risk, hence optimization of
      musculoskeletal health in men undergoing ADT is crucial. The role of exercise,
      and current and emerging anabolic therapies for muscle as well as various new
      strategies to prevent loss of bone mass in men undergoing ADT are discussed.
      Future well-designed, prospective, controlled studies are required to elucidate
      the effects of ADT on physical performance, which are currently lacking, and
      larger randomized controlled trials are required to test the efficacy of medical
      therapies and exercise interventions to target proven deficits and to ensure
      safety in men with prostate cancer. 

PMID- 25056177
TI  - The kinome associated with estrogen receptor-positive status in human breast
      cancer.
AB  - Estrogen receptor alpha (ERalpha) regulates and is regulated by kinases involved
      in several functions associated with the hallmarks of cancer. The following
      literature review strongly suggests that distinct kinomes exist for ERalpha
      positive and -negative human breast cancers. Importantly, consistent with the
      known heterogeneity of ERalpha-positive cancers, different subgroups exist, which
      can be defined by different kinome signatures, which in turn are correlated with
      clinical outcome. Strong evidence supports the interplay of kinase networks,
      suggesting that targeting a single node may not be sufficient to inhibit the
      network. Therefore, identifying the important hubs/nodes associated with each
      clinically relevant kinome in ER+ tumors could offer the ability to implement the
      best therapy options at diagnosis, either endocrine therapy alone or together
      with other targeted therapies, for improved overall outcome. 

PMID- 25056178
TI  - Outcome reliability in non-ambulatory boys/men with Duchenne muscular dystrophy.
AB  - INTRODUCTION: Therapeutic trials in Duchenne muscular dystrophy (DMD) often
      exclude non-ambulatory individuals. Here we establish optimal and reliable
      assessments in a multicenter trial. METHODS: Non-ambulatory boys/men with DMD (N
      = 91; 16.7 +/- 4.5 years of age) were assessed by trained clinical evaluators.
      Feasibility (percentage completing task) and reliability [intraclass correlation
      coefficients (ICCs) between morning and afternoon tests] were measured. RESULTS:
      Forced vital capacity (FVC), assessed in all subjects, showed a mean of 47.8 +/-
      22% predicted (ICC 0.98). Brooke Upper Extremity Functional Rating (Brooke) and
      Egen Klassifikation (EK) scales in 100% of subjects showed ICCs ranging from 0.93
      to 0.99. Manual muscle testing, range of motion, 9-hole peg test, and Jebsen
      Taylor Hand Function Test (JHFT) demonstrated varied feasibility (99% to 70%),
      with ICCs ranging from 0.99 to 0.64. We found beneficial effects of different
      forms of corticosteroids for the Brooke scale, percent predicted FVC, and hand
      and finger strength. CONCLUSIONS: Reliable assessment of non-ambulatory boys/men
      with DMD is possible. Clinical trials will have to consider corticosteroid use.

PMID- 25056179
TI  - Flavobacterium psychrophilum vaccine development: a difficult task.
AB  - Bacterial cold water disease (BCWD) is a globally distributed freshwater fish
      disease caused by the Gram-negative bacterium Flavobacterium psychrophilum. It is
      a particularly devastating infection in fry salmonids and may lead to high levels
      of mortality. In spite of its economic impact on fish farms, neither the biology
      of the bacterium nor the bacterium-host interactions are well understood. This
      review provides a synopsis of the major problems related to critical remaining
      questions about research into the use of vaccines against F. psychrophilum and
      the development of a commercial vaccine against this disease. Studies using sera
      from convalescent rainbow trout have shown the antigenic properties of different
      proteins such as OmpH, OmpA and FspA, as well as low and high molecular mass
      lipopolysaccharide of F. psychrophilum, which are potential candidates for
      subunit vaccines. Inactivated F. psychrophilum bacterins have been successfully
      tested as vaccines under laboratory conditions by both immersion and
      intraperitoneal routes. However, the efficacy and the practical usefulness of
      these preparations still have to be proved. The use of attenuated and wild-type
      strains to immunize fish showed that these systems offer high levels of
      protection. Nevertheless, their application clashes with the regulations for
      environmental protection in many countries. In conclusion, protective vaccines
      against BCWD are theoretically possible, but substantial efforts still have to be
      made in order to permit the development of a commercial vaccine. 

PMID- 25056180
TI  - SnipViz: a compact and lightweight web site widget for display and dissemination
      of multiple versions of gene and protein sequences.
AB  - BACKGROUND: As high throughput sequencing continues to grow more commonplace, the
      need to disseminate the resulting data via web applications continues to grow.
      Particularly, there is a need to disseminate multiple versions of related gene
      and protein sequences simultaneously--whether they represent alleles present in a
      single species, variations of the same gene among different strains, or homologs
      among separate species. Often this is accomplished by displaying all versions of
      the sequence at once in a manner that is not intuitive or space-efficient and
      does not facilitate human understanding of the data. Web-based applications
      needing to disseminate multiple versions of sequences would benefit from a drop
      in module designed to effectively disseminate these data. FINDINGS: SnipViz is a
      client-side software tool designed to disseminate multiple versions of related
      gene and protein sequences on web sites. SnipViz has a space-efficient,
      interactive, and dynamic interface for navigating, analyzing and visualizing
      sequence data. It is written using standard World Wide Web technologies (HTML,
      Javascript, and CSS) and is compatible with most web browsers. SnipViz is
      designed as a modular client-side web component and may be incorporated into
      virtually any web site and be implemented without any programming. CONCLUSIONS:
      SnipViz is a drop-in client-side module for web sites designed to efficiently
      visualize and disseminate gene and protein sequences. SnipViz is open source and
      is freely available at https://github.com/yeastrc/snipviz.

PMID- 25056182
TI  - The discovery and development of new potential antioxidant agents for the
      treatment of neurodegenerative diseases.
AB  - INTRODUCTION: Several neurodegenerative disorders (NDs) including Alzheimer's and
      Huntington's diseases have had associations with the oxidative process and free
      radical damage. Consequently, in past decades, several natural and synthetic
      antioxidants have been assessed as therapeutic agents but have shown limitations
      in bioavailability, metabolic susceptibility and permeability to the blood brain
      barrier. Given these issues, medicinal chemists are hard at work to
      modify/improve the chemical structures of these antioxidants, thereby improving
      their efficacy. AREAS COVERED: In this review, the authors critically analyze
      several biological mechanisms involved in the generation of free radicals.
      Additionally, they analyze free radicals' role in the generation of oxidative
      stress and in the progression of many NDs. Further, the authors review a
      collection of natural and synthetic antioxidants, their role as free radical
      scavengers along with their mechanisms of action and their potential for
      preventing neurodegenerative diseases. EXPERT OPINION: So far, preclinical
      studies on several antioxidants have shown promise for treating NDs, despite
      their limitations. The authors do highlight the lack of the adequate animal
      models for preclinical assessment and this does hinder further progression into
      clinical trials. Further studies are necessary to fully investigate the potential
      of these antioxidants as ND therapeutic options.

PMID- 25056183
TI  - Johns Hopkins Health System agrees to pay $190m to women filmed by doctor during
      pelvic exams.

PMID- 25056181
TI  - Evaluation of the anti-Listeria potentials of some plant-derived triterpenes.
AB  - BACKGROUND: Listeriosis is a fatal disease caused by pathogenic Listeria bacteria
      and it is most prevalent in immune-compromised individuals. The increase in
      numbers of immune-compromised individuals against a background of Listeria
      antibiotic resistance, limits listeriosis treatment options. This therefore calls
      for research into substitute treatments, of which, medicinal plants derived
      compounds offer a viable alternative. METHODS: The broth microdilution assay was
      used to determine the minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) of three plant triterpenes namely 3beta
      hydroxylanosta-9,24-dien-21-oic acid, methyl-3beta-hydroxylanosta-9,24-dien-21
      oate and 3beta-acetylursolic acid, against Listeria monocytogenes, Listeria
      ivanovii and Listeria grayi species. The chequerboard method was used to assess
      the interactions between the triterpenes and conventional antibiotics:
      ampicillin, neomycin, gentamicin and penicillin G. The lactate dehydrogenase
      membrane damage method was used to assess the triterpenes' membrane damaging
      potentials against the Listeria bacteria. RESULTS: The triterpenes' MIC values
      were found to range from 0.185 to 1.67 mg/ml while, the MBC determination assay
      results revealed that the test triterpenes were bacteriostatic against the
      Listeria bacteria. The interactions involving 3beta-hydroxylanosta-9,24-dien-21
      oic acid were mainly additive with ampicillin and synergistic with neomycin,
      gentamicin and penicillin G. The interactions involving methyl-3beta
      hydroxylanosta-9,24-dien-21-oate were mainly antagonistic with ampicillin,
      indifferent with neomycin, ranging from synergistic to indifference with
      gentamicin and synergistic with penicillin G. The interactions involving 3beta
      acetylursolic acid were mainly indifferent with ampicillin, synergistic with
      neomycin and gentamicin while ranging between synergistic and additive with
      penicillin G. The low levels of cytosolic lactate dehydrogenase released from the
      cells treated with 4* MIC concentration of the triterpenes in comparison to that
      of cells treated with 3% Triton X-100 proved that membrane damage was not the
      mode of action of the triterpenes. CONCLUSION: This study therefore shows the
      potential that these plant triterpenes have in listeriosis chemotherapy
      especially as shown by the favourable interactions they had with penicillin G,
      one of the antibiotics of choice in listeriosis treatment.

PMID- 25056184
TI  - Central adiposity after breast cancer diagnosis is related to mortality in the
      Health, Eating, Activity, and Lifestyle study.
AB  - We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after
      breast cancer diagnosis are associated with all-cause or breast cancer-specific
      mortality and explored potential biological pathways mediating these
      relationships. Our analysis included 621 women diagnosed with local or regional
      breast cancer who participated in the Health, Eating, Activity, and Lifestyle
      study. At 30 (+/-4) months postdiagnosis, trained staff measured participants'
      waist and hip circumferences and obtained fasting serum samples for biomarker
      assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and
      binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated
      multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over
      ~9.5 years of follow-up. After adjustment for measured body mass index,
      treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis
      physical activity, WC was positively associated with all-cause mortality
      (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast
      cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 %
      CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1:
      2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95
      % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score
      and C-reactive protein, risk estimates were attenuated and not statistically
      significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and
      WHR were associated with all-cause mortality. Insulin resistance and inflammation
      may mediate the effects of central adiposity on mortality among breast cancer
      patients. 

PMID- 25056185
TI  - Ghrelin and des-acyl ghrelin inhibit aromatase expression and activity in human
      adipose stromal cells: suppression of cAMP as a possible mechanism.
AB  - Aromatase converts androgens into estrogens and its expression within adipose
      stromal cells (ASCs) is believed to be the major driver of estrogen-dependent
      cancers in older women. Ghrelin is a gut-hormone that is involved in the
      regulation of appetite and known to bind to and activate the cognate ghrelin
      receptor, GHSR1a. The unacylated form of ghrelin, des-acyl ghrelin, binds weakly
      to GHSR1a but has been shown to play an important role in regulating a number of
      physiological processes. The aim of this study was to determine the effect of
      ghrelin and des-acyl ghrelin on aromatase in primary human ASCs. Primary human
      ASCs were isolated from adipose tissue of women undergoing cosmetic surgery. Real
      time PCR and tritiated water-release assays were performed to examine the effect
      of treatment on aromatase transcript expression and aromatase activity,
      respectively. Treatments included ghrelin, des-acyl ghrelin, obestatin, and
      capromorelin (GHSR1a agonist). GHSR1a protein expression was assessed by Western
      blot and effects of treatment on Ca(2+) and cAMP second messenger systems were
      examined using the Flexstation assay and the Lance Ultra cAMP kit, respectively.
      Results demonstrate that pM concentrations of ghrelin and des-acyl ghrelin
      inhibit aromatase transcript expression and activity in ASCs under basal
      conditions and in PGE2-stimulated cells. Moreover, the effects of ghrelin and des
      acyl ghrelin are mediated via effects on aromatase promoter PII-specific
      transcripts. Neither the GHSR1a-specific agonist capromorelin nor obestatin had
      any effect on aromatase transcript expression or activity. Moreover, GHSR1a
      protein was undetectable by Western blot and neither ghrelin nor capromorelin
      elicited a calcium response in ASCs. Finally, ghrelin caused a significant
      decrease in basal and forskolin-stimulated cAMP in ASC. These findings suggest
      that ghrelin acts at alternate receptors in ASCs by decreasing intracellular cAMP
      levels. Ghrelin mimetics may be useful in the treatment of estrogen-dependent
      breast cancer. 

PMID- 25056186
TI  - Reasons for emergency room use among U.S. children: National Health Interview
      Survey, 2012.
AB  - KEY FINDINGS: Data from the National Health Interview Survey, 2012. In 2012,
      children with Medicaid coverage were more likely than uninsured children and
      those with private coverage to have visited the emergency room (ER) at least once
      in the past year. About 75% of children's most recent visits to an ER in the past
      12 months took place at night or on a weekend, regardless of health insurance
      coverage status. The seriousness of the medical problem was less likely to be the
      reason that children with Medicaid visited the ER at their most recent visit
      compared with children with private insurance. Among children whose most recent
      visit to the ER was for reasons other than the seriousness of the medical
      problem, the majority visited the ER because the doctor's office was not open.
      Emergency rooms (ERs) are intended to provide care for acute and life-threatening
      medical conditions for people of all ages, but use is highest among older adults
      and young children (1). In 2012, 18% of children aged 0-17 years visited the ER
      at least once in the past year (2). Rising health care costs make it important to
      understand the reasons that families with children seek ER care, rather than less
      expensive office-based or outpatient care (3). Families visiting the ER at night
      or on weekends may have different characteristics or reasons for using the ER
      than those who visit during the day (4). Previous research among adults found
      that the majority visited the ER because "only a hospital could help," or the
      "doctor's office [was] not open" (5). This report provides comparable statistics
      on reasons for children's ER use.

PMID- 25056187
TI  - Structure and photoluminescence properties of a rare-earth free red-emitting
      Mn(2+)-activated KMgBO3.
AB  - In this combined X-ray diffraction and photoluminescence study, the coordination
      environment of Mn(2+) and the photoluminescence of single Mn(2+) doped KMgBO3
      phosphors were studied. Mn(2+) occupies Mg(2+) sites, which were coordinated by
      six O(2-). The strong absorption of KMgBO3:Mn(2+) was ascribed to the strong
      relaxation of spin and parity forbidden d-d transitions of Mn(2+). The emission
      bands were centered at 636 nm, regardless of the excitation wavelength and Mn(2+)
      doping concentration. Mn(2+) activated KMgBO3 could be efficiently excited with
      the excitation of Mn(2+) d-d transitions in the wavelength range of 300-475 nm.
      The red-shift of Mn(2+) emission was because of the strong crystal field
      environment of Mn(2+) afforded by KMgBO3. The potential applications of the
      phosphors have been pointed out based on their absorption spectra, excitation and
      emission spectra, thermal quenching properties, and decay properties. 

PMID- 25056188
TI  - Label-free electrochemiluminescent enantioselective sensor for distinguishing
      between chiral metallosupramolecular complexes.
AB  - Chiral molecular recognition of DNA is important for rational drug design and for
      developing structural probes of DNA conformation. Developing a convenient and
      inexpensive assay for sensitive and selective identification of DNA-specific
      binding compounds with rapid, easy manipulation is in ever-increasing demand.
      Here, we present a "turn-on" and label-free electrochemiluminescent (ECL)
      biosensor for distinguishing chiral metallosupramolecular complexes based on DNA
      three-way junction formation selectively induced by the analyte. The fabricated
      ECL sensor shows excellent performance in the chiral discrimination of two
      enantiomers with an enantioselective recognition ratio of up to 4.4. More
      importantly, as a "turn-on" detection system, the ECL chiral sensor does not
      suffer from false positives and limited signal range of "signal-off" systems.
      Therefore, this concept may provide a new insight into the design of efficient
      sensors for distinguishing chiral molecules and for investigating the
      interactions between DNA and small molecules. 

PMID- 25056190
TI  - The effect of the type of pain on the accuracy of memory of pain and affect.
AB  - BACKGROUND: Memory of chronic, acute and experimental pain may be inaccurate, but
      the research findings are inconsistent. The main aim of the study was to compare
      the memory of three types of pain and their associated affect. METHODS: A total
      of 140 women, who gave birth by vaginal delivery or Caesarean section, or
      underwent gynaecological surgery, participated in the study. Before childbirth or
      surgery, the women rated their anxiety about the pain they would experience.
      Between 24 and 48 h after childbirth or surgery, they rated the intensity and
      unpleasantness of the pain, and their positive and negative affect. Either 3 or 6
      months later, the participants recalled the pain and affect they had felt.
      RESULTS: The study found that the type of pain had an effect on memory of pain
      and affect. Surgery led to an overestimation of all but one of the recalled
      variables. Participants who gave birth by Caesarean section were the most
      accurate at recalling pain and affect. Memories of pain and affect were most
      variable in participants who gave birth by vaginal delivery. The three groups of
      participants differed in terms of the predictors of recalled pain intensity and
      unpleasantness, and the proportion of variance predicted by the same independent
      variables. CONCLUSIONS: The results of the current study suggest that memory of
      pain and affect is influenced by the meaning and affective value of the pain
      experience. This may help us to understand why the previous research on the
      memory of pain were so diverse.

PMID- 25056191
TI  - Tissue transglutaminase on trophoblast cells as a possible target of
      autoantibodies contributing to pregnancy complications in celiac patients.
AB  - PROBLEM: Women with celiac disease (CD) are often affected by atypical
      presentations of the disease associated with reproductive disorders as a main
      extra-digestive complaint. Here, we analyzed if autoantibodies against tissue
      transglutaminase (tTG) in sera from CD patients with reproductive disorders could
      display direct effects through their interaction with tTG expressed on
      trophoblast cells and phagocytes inducing tissue damage and interfering in the
      clearance of trophoblast apoptotic bodies. METHOD OF STUDY: Sera from CD women
      with reproductive disorders were obtained, and their ability to induce apoptosis
      of Swan-71 (cytotrophoblast cell line) and to modulate the wound-healing and
      phagocytes process was tested. RESULTS: Swan-71 cells expressed tTG and CD sera
      displayed a significant decrease in trophoblast cell migration and a delay in
      injury healing on trophoblast cells, compared with those observed with control
      sera. Moreover, CD sera significantly reduced trophoblast cell proliferation and
      increased apoptosis levels in comparison with those observed in the control sera.
      Finally, autoantibodies against tTG interfere in the clearance of trophoblast
      apoptotic bodies through a mechanism involving MFG-E8 (milk fat globulin-EGF
      factor 8)-tTG binding. CONCLUSION: The anti-tTG antibodies might contribute to
      trophoblast damage and disrupt the phagocytosis process of apoptotic bodies that
      could promote a pro-inflammatory microenvironment.

PMID- 25056192
TI  - Revealing the active intermediates in the oxidation of formic acid on Au and
      Pt(111).
AB  - The mechanisms of formic acid (HCOOH) oxidation on Au(111) under gas-phase and
      electrochemical conditions was studied by using density functional theory and
      then compared with the analogous processes on Pt(111). Our results demonstrate
      that a mechanism involving a single intermediate molecule is preferred on both Au
      and Pt(111). Furthermore, under gas-phase conditions, HCOOH oxidation proceeds
      through the same mechanism (formate pathway) on Au and Pt(111), whereas under
      electrochemical conditions, it can take place through significantly different
      mechanisms (formate and/or direct pathways), depending on the applied electrode
      potential. Our calculations help to rationalize conflicting experimental
      explanations and are crucial for understanding the mechanism of this fundamental
      (electro-)catalytic process. 

PMID- 25056193
TI  - Redefining the DNA-binding domain of human XPA.
AB  - Xeroderma pigmentosum complementation group A (XPA) protein plays a critical role
      in the repair of DNA damage via the nucleotide excision repair (NER) pathway. XPA
      serves as a scaffold for NER, interacting with several other NER proteins as well
      as the DNA substrate. The critical importance of XPA is underscored by its
      association with the most severe clinical phenotypes of the genetic disorder
      Xeroderma pigmentosum. Many of these disease-associated mutations map to the
      XPA(98-219) DNA-binding domain (DBD) first reported ~20 years ago. Although
      multiple solution NMR structures of XPA(98-219) have been determined, the
      molecular basis for the interaction of this domain with DNA is only poorly
      characterized. In this report, we demonstrate using a fluorescence anisotropy DNA
      binding assay that the previously reported XPA DBD binds DNA with substantially
      weaker affinity than the full-length protein. In-depth analysis of the XPA
      sequence suggested that the original DBD construct lacks critical basic charge
      and helical elements at its C-terminus. Generation and analysis of a series of C
      terminal extensions beyond residue 219 yielded a stable, soluble human XPA(98
      239) construct that binds to a Y-shaped ssDNA-dsDNA junction and other substrates
      with the same affinity as the full-length protein. Two-dimensional (15)N-(1)H NMR
      suggested XPA(98-239) contains the same globular core as XPA98-219 and likely
      undergoes a conformational change upon binding DNA. Together, our results
      demonstrate that the XPA DBD should be redefined and that XPA(98-239) is a
      suitable model to examine the DNA binding activity of human XPA.

PMID- 25056194
TI  - Long latency trigemino-cervical reflex in patients with cervical dystonia.
AB  - Trigemino-cervical reflex (TCR) is elicited by stimulation of face using various
      modalities. TCR reflects the interaction between trigeminal system and cervical
      motoneurons. Such a specific interaction is assumed to play role in development
      of cervical dystonia (CD) through superior colliculus. In this study, we aimed to
      investigate alterations of the functional relationship between those structures
      in CD and in a subgroup with dystonic tremor. A total of consecutive 23 patients
      with primary CD (7 men, 16 women) and 16 age and sex matched control subjects (7
      men, 9 women) were included in this study. TCR was obtained after percutaneous
      electrical stimulation (with duration of 0.5 ms) of infraorbital branch of
      trigeminal nerve while recording over splenius capitis and sternocleidomastoid
      muscles. Presence and onset latencies of TCR did not differ significantly between
      patients with CD and controls, and same pattern of muscle activation occurred in
      both groups. Responses of patient group seemed to have higher amplitudes and to
      be more persistent. There were no significant side-to-side differences of TCR
      probability, latency, amplitude or duration with respect to the side of head
      deviation in CD. Increased amplitudes and durations of responses probably reflect
      increased excitability of the reflex circuit. We suggest that similar latencies
      and response pattern in comparison to healthy individuals decrease the
      possibility of structural disturbance. TCR is probably under bilateral basal
      ganglia and dopaminergic control. Alterations of trigemino-cervical pathway are
      more extensive and are not solely due to local changes of brainstem interneurons.

PMID- 25056195
TI  - Approaching a brainstem high-grade glioma (HGG) with the assistance of 5
      aminolevulinic acid (5-ALA) technology: a new strategy for an old surgical
      challenge.

PMID- 25056196
TI  - Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited.
AB  - High dose pyridoxine is neurotoxic. Previous case reports were sparse and little
      is known about the clinical and electrodiagnostic findings. Three patients with
      pyridoxine-induced sensory ataxic neuropathy were studied and a review of the
      involved literature was performed. Three patients, aged 80, 83 and 83 years old,
      presented with sensory ataxia for 3-8 months. Examination showed signs of
      polyneuropathy and sensory ataxia. Six hundred milligrams of pyridoxine was
      consumed each day for 3-10 years, in the form of vitamin B1-6-12 combination
      tablet. Investigations for other causes of neuropathy were unremarkable. Blood
      levels of vitamin B6 were markedly elevated at 104.6, 81.4 and 66.9 times of
      upper normal limits. Electrodiagnostic tests showed symmetric axonal sensory
      polyneuropathy in two patients. Two years after vitamin discontinuation, all
      patients showed no significant improvement in the neuropathy and gait. In
      conclusion, consumption of high dose pyridoxine can cause sensory neuronopathy
      and axonal sensorimotor polyneuropathy, leading to sensory ataxia which may not
      be reversible.

PMID- 25056197
TI  - An in situ synthesis of mesoporous SBA-16/hydroxyapatite for ciprofloxacin
      release: in vitro stability and cytocompatibility studies.
AB  - The present work developed a biomaterial (HA/SBA-16) based on the growth of
      calcium phosphate (HA) particles within an organized silica structure (SBA-16) to
      evaluate its application as a drug delivery system. The samples were charged with
      ciprofloxacin as a model drug and in vitro release assays were carried out. The
      samples were characterized by elemental analysis (CHN), Fourier transform
      infrared spectroscopy, nitrogen adsorption, scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), small angle X-ray scattering (SAXS) and X
      ray diffraction. The results obtained by TEM, SEM and SAXS reveal a well-defined
      cubic arrangement of a uniform spherical mesoporous structure, an intrinsic
      characteristic of these materials, which indicated that SBA-16 and HA/SBA-16
      could potentially encapsulate bioactive molecules by means of ordered mesopores.
      It was found that both surface interaction and pore volume affect the rate and
      amount of ciprofloxacin released from the mesoporous materials. In vitro assays
      were performed to evaluate the adhesion, viability, and growth behavior of human
      adipose tissue-derived stem cells (hADSC) on SBA-16 and HA/SBA-16 nanocomposites
      to verify their potential as a scaffold for application in bone-tissue
      engineering using MTT assay and alkaline phosphatase activity tests. The results
      showed that the materials are promising systems for bone repair, providing a good
      environment for the adhesion and proliferation of rat mesenchymal stem cells and
      hADSC in vitro. 

PMID- 25056198
TI  - Reduced fibroblast adhesion and proliferation on plasma-modified titanium
      surfaces.
AB  - Soft tissue complications are clinically relevant problems after osteosynthesis
      of fractures. The goal is to develop a method for reduction of fibroblast
      adhesion and proliferation on titanium implant surfaces by plasma polymerisation
      of the organo-silicon monomer hexamethyldisiloxane (HMDSO). HMDSO was deposited
      under continuous wave conditions in excess oxygen (ppHMDSO surface) and selected
      samples were further modified with an additional oxygen plasma (ppHMDSO + O2
      surface). Surface characterization was performed by scanning electron microscopy,
      profilometry, water contact angle measurements, infrared reflection absorption
      spectroscopy and X-ray photoelectron spectroscopy. In our experimental setup the
      mechanical properties, roughness and topography of the titanium were preserved,
      while surface chemistry was drastically changed. Fibroblast proliferation was
      assessed by alamarBlue assay, cell morphology by confocal microscopy
      visualization of eGFP-transducted fibroblasts, and cell viability by Annexine
      V/propidium iodide assay. Both modified surfaces, non-activated hydrophobic
      ppHMDSO and activated hydrophilic ppHMDSO + O2 were able to dramatically reduce
      fibroblast colonization and proliferation compared to standard titanium. However,
      this effect was more strongly pronounced on the hydrophobic ppHMDSO surface,
      which caused reduced cell adhesion and prevented proliferation of fibroblasts.
      The results demonstrate that plasma modifications of titanium using HMDSO are
      valuable candidates for future developments in anti-adhesive and anti
      proliferative coatings for titanium fracture implants.

PMID- 25056199
TI  - Three-dimensional culture in a microgravity bioreactor improves the engraftment
      efficiency of hepatic tissue constructs in mice.
AB  - Tissue-engineered liver using primary hepatocytes has been considered a valuable
      new therapeutic modality as an alternative to whole organ liver transplantation
      for different liver diseases. The development of clinically feasible liver tissue
      engineering approaches, however, has been hampered by the poor engraftment
      efficiency of hepatocytes. We developed a three-dimensional (3D) culture system
      using a microgravity bioreactor (MB), biodegradable scaffolds and growth-factor
      reduced Matrigel to construct a tissue-engineered liver for transplantation into
      the peritoneal cavity of non-obese diabetic severe combined immunodeficient mice.
      The number of viable cells in the hepatic tissue constructs was stably maintained
      in the 3D MB culture system. Hematoxylin-eosin staining and zonula occludens-1
      expression revealed that neonatal mouse liver cells were reorganized to form
      tissue-like structures during MB culture. Significantly upregulated hepatic
      functions (albumin secretion, urea production and cytochrome P450 activity) were
      observed in the MB culture group. Post-transplantation analysis indicated that
      the engraftment efficiency of the hepatic tissue constructs prepared in MB
      cultures was higher than that of those prepared in the static cultures. Higher
      level of hepatic function in the implants was confirmed by the expression of
      albumin. These findings suggest that 3D MB culture systems may offer an improved
      method for creating tissue-engineered liver because of the higher engraftment
      efficiency and the reduction of the initial cell function loss. 

PMID- 25056200
TI  - Multilayered implantation using acellular dermal matrix into nude mice.
AB  - Soft tissue augmentation using acellular dermal matrix has gained popularity to
      overcome the shortcomings of autogenous and alloplastic materials. Sometimes it
      needs multilayered stacking to obtain enough volume. In this study, we
      investigated the efficacy of multilayered implantation using acellular dermal
      matrix (MatriDerm((r))) for soft tissue augmentation. MatriDerm was implanted
      subdermally on each side of the dorsum of nude mice (n = 20), stacked two layers
      thick in the control group and three layers thick in the experimental group.
      Alterations of thickness, degree of angiogenesis, and collagen and elastin fiber
      syntheses were observed over 40 days. Three-layered implantation with MatriDerm
      maintained its volume similarly as in two-layered implantation, although the
      thickness decreased after 30 days in both groups. At the early stage of
      implantation, angiogenesis and collagen and elastin fiber syntheses occurred
      fluently on the central portion, which is the farthest away from the surface in
      contact with the host tissue. Collagen and elastin fibers became more
      concentrated over time, and the original structure of MatriDerm could not be
      maintained due to being replaced with newly formed collagen and elastin fibers 40
      days after implantation. Multilayered implantation with MatriDerm is considered
      appropriate for tissue ingrowth and can be used as a substitute for soft tissue
      augmentation. 

PMID- 25056201
TI  - Advanced medical students' experiences and views on professionalism at Kuwait
      University.
AB  - BACKGROUND: Professionalism is a core competency in the medical profession
      worldwide. Numerous studies investigate how this competency is taught and
      learned. However, there are few reports on the students' views and experiences
      with professionalism especially in the Arab world. Our aim was to explore the
      experiences and views of Kuwait final-year medical students on professionalism.
      METHODS: This was a questionnaire study of final-year medical students at Kuwait
      University (n = 95). Open- and close-ended questions were used to determine the
      students' experiences and views on: definition, teaching, learning, and
      assessment of professionalism. RESULTS: Eighty-five of the students completed the
      questionnaire (89.5%). A total of 252 attributes defining professionalism were
      listed by our respondents. The majority (98.0%) of these attributes were
      categorized under the CanMEDS theme describing professionalism as commitment to
      patients, profession, and society through ethical practice. The most helpful
      methods in learning about professionalism for the students were contact with
      positive role models, patients and families, and with their own families,
      relatives and peers. The students' rating of the quality and quantity of teaching
      professionalism in the institution was quite variable. Despite this, 68.2% of the
      students felt very or somewhat comfortable explaining the meaning of medical
      professionalism to junior medical students. Almost half of the students felt that
      their education had always or sometimes helped them deal with professionally
      challenging situations. Majority (77.6%) of the students thought that their
      academic assessments should include assessment of professionalism and should be
      used as a selection criterion in their future academic careers (62.3%). Most of
      the students discussed and sought advice regarding professionally-challenging
      situations from their fellow medical students and colleagues. Seventy-five
      (88.2%) students did not know which organizational body in the institution deals
      with matters pertaining to medical professionalism. CONCLUSION: This study
      highlights the influence of the curriculum, the hidden curriculum, and culture on
      medical students' perception of professionalism. Medical educators should take in
      account such influences when teaching and assessing professionalism. Future
      research should aim at creating a framework of competencies that addresses
      professionalism in a context suitable for the Arabian culture.

PMID- 25056202
TI  - Detection of abnormal circumflex artery from the right coronary sinus in a
      patient scheduled for root aneurysm repair.

PMID- 25056203
TI  - ROR1 expression correlated with poor clinical outcome in human ovarian cancer.
AB  - The receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is a transmembrane
      protein belongs to receptor tyrosine kinase (RTK) family. This study aimed to
      examine the expression of ROR1 in human ovarian cancer and investigate the
      relationship between its expression and the prognosis of ovarian cancer patients.
      In this present study, one-step quantitative reverse transcription-polymerase
      chain reaction (15 ovarian cancer samples of high FIGO stage, 15 ovarian cancer
      samples of low FIGO stage and nine normal ovary tissue samples) and
      immunohistochemistry by tissue microarrays (100 ovarian cancer samples and 50
      normal ovary samples) were performed to characterize expression of the ROR1 gene
      in ovarian cancer. Kaplan-Meier survival and Cox regression analyses were
      executed to evaluate the prognosis of ovarian cancer. The results of qPCR and IHC
      analysis showed that the expression of ROR1 in ovarian cancer was significantly
      higher than that in normal ovary tissues (all p < 0.05). Survival analysis showed
      that ROR1 protein expression was one of the independent prognostic factors for
      disease-free survival and overall survival (both p < 0.05). The data suggest that
      ROR1 expression is correlated with malignant attributes of ovarian cancer and it
      may serve as a novel prognostic marker in ovarian cancer. 

PMID- 25056204
TI  - Tuning hydrogen storage in lithium-functionalized BC2N sheets by doping with
      boron and carbon.
AB  - First-principles calculations are used to explore the strong binding of lithium
      to boron- and carbon-doped BC2N monolayers (BC2NBC and BC2NCN, respectively)
      without the formation of lithium clusters. In comparison to BC2N and BC2NCB,
      lithium-decorated BC2NBC and BC2NCN systems possess stronger s-p and p-p
      hybridization and, hence, the binding energy is higher. Lithium becomes partially
      positively charged by donating electron density to the more electronegative atoms
      of the sheet. Attractive van der Waals interactions are responsible for binding
      hydrogen molecules around the lithium atoms. Each lithium atom can adsorb three
      hydrogen molecules on both sides of the sheet, with an average hydrogen binding
      energy of approximately 0.2 eV, which is in the range required for practical
      applications. The BC2NBC-Li and BC2NCN-Li complexes can serve as high-capacity
      hydrogen-storage media with gravimetric hydrogen capacities of 9.88 and 9.94 wt
      %, respectively.

PMID- 25056205
TI  - Aromatase inhibitors associated musculoskeletal disorders and bone fractures in
      postmenopausal breast cancer patients: a result from Chinese population.
AB  - As the prognosis of early breast cancer patients improves, the long-term safety
      of aromatase inhibitors (AIs) is increasingly important. In the present study, we
      retrospectively investigated the incidences of musculoskeletal disorders (MSDs)
      and bone fractures in a cohort of Chinese postmenopausal patients with breast
      cancer. Data of postmenopausal patients with breast cancer were collected. Among
      which, 70 patients received AIs therapy (median follow-up of 32.5 months), 52
      patients received tamoxifen (TAM), and 89 patients received no endocrine therapy
      (NE). Baseline characteristics, incidence of MSDs and bone fractures were
      analyzed and compared. When compared with NE group (40.4 %, 36/89), more patients
      in AIs group developed MSDs (72.9 %, 51/70, adjusted odds ratio (AOR) = 3.30, 95
      % confidence interval (CI) = 1.59-6.88, P = 0.001). But no difference was found
      between TAM group (36.5 %, 19/52, AOR = 0.70, 95 % CI = 0.32-1.52, P = 0.372) and
      NE group. About 39.7 months after initial AIs therapy, nine patients in AI group
      developed bone fractures in different sites, and the bone fracture rate was
      significantly increased (12.9 %, 9/70, adjusted hazard ratio (AHR) = 20.08, 95 %
      CI = 1.72-234.08, P = 0.017) in comparison with NE group (1.1 %, 1/89). Moreover,
      the bone fracture rate of TAM group was not different from NE group (1.9 %, 1/52,
      AHR = 2.64, 95 % CI = 0.14-48.73, P = 0.513). AIs therapy may induce increased
      rates of MSDs and bone fractures in Chinese population of postmenopausal breast
      cancer patients, whereas TAM therapy did not help reduce the incidences of MSDs
      and bone fractures.

PMID- 25056206
TI  - Preoperative imatinib facilitates complete resection of locally advanced primary
      GIST by a less invasive procedure.
AB  - Complete resection is the most effective therapy for gastrointestinal stromal
      tumors (GISTs). Complete resection of locally advanced primary GIST by less
      invasive procedure is usually difficult at initial diagnosis. Imatinib has been
      successful in treating locally advanced and metastatic GIST and this report
      shares the experiences in preoperative use of imatinib for patients with locally
      advanced primary GISTs. The procedure of treatment and completeness of resection
      were retrospectively accessed for locally advanced primary GIST. Disease-free
      survival (DFS) and overall survival (OS) after resection were analyzed. Thirteen
      patients were treated with imatinib preoperatively. All patients received
      surgical resection after a median imatinib treatment of 7 months when most tumors
      shrunk. All patients achieved R0 resection without tumor rupture. Two patients
      received an en-bloc multivisceral resection for the invasion of surrounding
      organs and 3 patients underwent Mile's operation for a low rectal tumor. Eleven
      patients were disease-free. Median DFS or OS had not been reached, while 1- and 3
      year DFS were estimated to be 92.3 and 76.9 %, respectively. 1- and 3-year OS
      were both estimated to be 100 %. Preoperative use of imatinib is useful in
      locally advanced primary GIST by downsizing the tumor in most patients and
      facilitating complete resection through less invasive procedures without tumor
      rupture.

PMID- 25056207
TI  - 'You shall not pass!': quantifying barrier permeability and proximity avoidance
      by animals.
AB  - Impediments to animal movement are ubiquitous and vary widely in both scale and
      permeability. It is essential to understand how impediments alter ecological
      dynamics via their influence on animal behavioural strategies governing space use
      and, for anthropogenic features such as roads and fences, how to mitigate these
      effects to effectively manage species and landscapes. Here, we focused primarily
      on barriers to movement, which we define as features that cannot be
      circumnavigated but may be crossed. Responses to barriers will be influenced by
      the movement capabilities of the animal, its proximity to the barriers, and
      habitat preference. We developed a mechanistic modelling framework for
      simultaneously quantifying the permeability and proximity effects of barriers on
      habitat preference and movement. We used simulations based on our model to
      demonstrate how parameters on movement, habitat preference and barrier
      permeability can be estimated statistically. We then applied the model to a case
      study of road effects on wild mountain reindeer summer movements. This framework
      provided unbiased and precise parameter estimates across a range of strengths of
      preferences and barrier permeabilities. The quality of permeability estimates,
      however, was correlated with the number of times the barrier is crossed and the
      number of locations in proximity to barriers. In the case study we found that
      reindeer avoided areas near roads and that roads are semi-permeable barriers to
      movement. There was strong avoidance of roads extending up to c. 1 km for four of
      five animals, and having to cross roads reduced the probability of movement by
      68.6% (range 3.5-99.5%). Human infrastructure has embedded within it the idea of
      networks: nodes connected by linear features such as roads, rail tracks,
      pipelines, fences and cables, many of which divide the landscape and limit animal
      movement. The unintended but potentially profound consequences of infrastructure
      on animals remain poorly understood. The rigorous framework for simultaneously
      quantifying movement, habitat preference and barrier permeability developed here
      begins to address this knowledge gap. 

PMID- 25056208
TI  - Rationale and design of the research project of the South Florida Center for the
      Reduction of Cancer Health Disparities (SUCCESS): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: In the United States certain minority groups, such as racial/ethnic
      immigrant women, are less likely than non-Hispanic White women to be screened for
      cervical cancer. Barriers to such care include health insurance, cost, knowledge,
      attitudes, health literacy, and cultural norms and practices. Among the most
      promising approaches to increase screening in these groups are patient navigators
      that can link women to sources of appropriate care. Another recent promising
      approach is using human papilloma virus (HPV) self-sampling. In this manuscript,
      we describe our National Cancer Institute-sponsored study testing such approaches
      among immigrant minority women. DESIGN: The South Florida Center for the
      Reduction of Cancer Health Disparities (SUCCESS) is conducting a three-arm
      randomized trial among Hispanic, Haitian, and African American women in Miami
      Dade County. Community health workers (CHW) based in each of three communities
      are recruiting 200 women at each site (600 total). Eligibility criteria include
      women aged 30-65 years who have not had a Pap smear test in the last 3 years.
      Prior to randomization, all women undergo a standardized structured interview.
      Women randomized to public health outreach, Group 1, receive culturally tailored
      educational materials. Women in Group 2 receive an individualized comprehensive
      cervical cancer CHW-led education session followed by patient navigation to
      obtain the Pap smear test at community-based facilities. Women in Group 3 have
      the option of navigation to a Pap smear test or performing HPV self-sampling. The
      primary outcome is self-report of completed screening through a Pap smear test or
      HPV self-sampling within 6 months after enrollment. DISCUSSION: SUCCESS is one of
      the first trials testing HPV self-sampling as a screening strategy among
      underserved minority women. If successful, HPV self-sampling may be an important
      option in community outreach programs aimed at reducing disparities in cervical
      cancer. TRIAL REGISTRATION: Clinical Trials.gov # NCT02121548, registered April
      21, 2014.

PMID- 25056209
TI  - Synthesis of isocoumarins through three-component couplings of arynes, terminal
      alkynes, and carbon dioxide catalyzed by an NHC-copper complex.
AB  - A copper-catalyzed multicomponent coupling reaction between in situ generated
      ortho-arynes, terminal alkynes, and carbon dioxide was developed to access
      isocoumarins in moderate to good yields. The key to this CO2-incorporating
      reaction was the use of a versatile N-heterocyclic carbene/copper complex that
      was able to catalyze multiple transformations within the three-component
      reaction.

PMID- 25056210
TI  - Myelination, oligodendrocytes, and serious mental illness.
AB  - Historically, the human brain has been conceptually segregated from the periphery
      and further dichotomized into gray matter (GM) and white matter (WM) based on the
      whitish appearance of the exceptionally high lipid content of the myelin sheaths
      encasing neuronal axons. These simplistic dichotomies were unfortunately extended
      to conceptually segregate neurons from glia, cognition from behavior, and have
      been codified in the separation of clinical and scientific fields into medicine,
      psychiatry, neurology, pathology, etc. The discrete classifications have helped
      obscure the importance of continual dynamic communication between all brain cell
      types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2)
      cells) as well as between brain and periphery through multiple signaling systems.
      The signaling systems range from neurotransmitters to insulin, angiotensin, and
      multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help
      integrate metabolism, inflammation, and myelination processes and orchestrate the
      development, plasticity, maintenance, and repair that continually optimize
      function of neural networks. A more comprehensive, evolution-based, systems
      biology approach that integrates brain, body, and environmental interactions may
      ultimately prove more fruitful in elucidating the complexities of human brain
      function. The historic focus on neurons/GM is rebalanced herein by highlighting
      the importance of a systems-level understanding of the interdependent age-related
      shifts in both central and peripheral homeostatic mechanisms that can lead to
      remarkably prevalent and devastating neuropsychiatric diseases. Herein we
      highlight the role of glia, especially the most recently evolved oligodendrocytes
      and the myelin they produce, in achieving and maintaining optimal brain function.
      The human brain undergoes exceptionally protracted and pervasive myelination
      (even throughout its GM) and can thus achieve and maintain the rapid conduction
      and synchronous timing of neural networks on which optimal function depends. The
      continuum of increasing myelin vulnerability resulting from the human brain's
      protracted myelination underlies underappreciated communalities between different
      disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and
      bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD).
      These shared vulnerabilities also expose significant yet underexplored
      opportunities for novel treatment and prevention approaches that have the
      potential to considerably reduce the tremendous burden of neuropsychiatric
      disease.

PMID- 25056211
TI  - The structure and mechanics of Moso bamboo material.
AB  - Although bamboo has been used structurally for millennia, there is currently
      increasing interest in the development of renewable and sustainable structural
      bamboo products (SBPs). These SBPs are analogous to wood products such as
      plywood, oriented strand board and glue-laminated wood. In this study, the
      properties of natural Moso bamboo (Phyllostachys pubescens) are investigated to
      further enable the processing and design of SBPs. The radial and longitudinal
      density gradients in bamboo give rise to variations in the mechanical properties.
      Here, we measure the flexural properties of Moso bamboo in the axial direction,
      along with the compressive strengths in the axial and transverse directions.
      Based on the microstructural variations (observed with scanning electron
      microscopy) and extrapolated solid cell wall properties of bamboo, we develop
      models, which describe the experimental results well. Compared to common North
      American construction woods loaded along the axial direction, Moso bamboo is
      approximately as stiff and substantially stronger, in both flexure and
      compression but denser. This work contributes to critical knowledge surrounding
      the microstructure and mechanical properties of bamboo, which are vital to the
      engineering and design of sustainable SBPs. 

PMID- 25056212
TI  - Ultrasonic emissions reveal individual cavitation bubbles in water-stressed wood.
AB  - Under drought conditions, the xylem of trees that conducts ascending sap produces
      ultrasonic emissions whose exact origin is not clear. We introduce a new method
      to record simultaneously both acoustic events and optical observation of the
      xylem conduits within slices of wood that were embedded in a transparent material
      setting a hydric stress. In this article, we resolved the rapid development of
      all cavitation bubbles and demonstrated that each ultrasound emission was linked
      to the nucleation of one single bubble, whose acoustic energy is an increasing
      function of the size of the conduit where nucleation occurred and also of the
      hydric stress. We modelled these observations by the fact that water columns in
      conduits store elastic energy and release it into acoustic waves when they are
      broken by cavitation bubbles. Water columns are thus elastic, and not rigid,
      'wires of water' set under tension by hydric stresses. Cavitation bubbles are at
      the origin of an embolism, whose development was followed in our experiments.
      Such an embolism of sap circulation can result in a fatal condition for living
      trees. These findings provide new insights for the non-destructive monitoring of
      embolisms within trees, and suggest a new approach to study porous media under
      hydric stress. 

PMID- 25056213
TI  - Optimal orientation in flows: providing a benchmark for animal movement
      strategies.
AB  - Animal movements in air and water can be strongly affected by experienced flow.
      While various flow-orientation strategies have been proposed and observed, their
      performance in variable flow conditions remains unclear. We apply control theory
      to establish a benchmark for time-minimizing (optimal) orientation. We then
      define optimal orientation for movement in steady flow patterns and, using
      dynamic wind data, for short-distance mass movements of thrushes (Turdus sp.) and
      6000 km non-stop migratory flights by great snipes, Gallinago media. Relative to
      the optimal benchmark, we assess the efficiency (travel speed) and reliability
      (success rate) of three generic orientation strategies: full compensation for
      lateral drift, vector orientation (single-heading movement) and goal orientation
      (continually heading towards the goal). Optimal orientation is characterized by
      detours to regions of high flow support, especially when flow speeds approach and
      exceed the animal's self-propelled speed. In strong predictable flow (short
      distance thrush flights), vector orientation adjusted to flow on departure is
      nearly optimal, whereas for unpredictable flow (inter-continental snipe flights),
      only goal orientation was near-optimally reliable and efficient. Optimal
      orientation provides a benchmark for assessing efficiency of responses to complex
      flow conditions, thereby offering insight into adaptive flow-orientation across
      taxa in the light of flow strength, predictability and navigation capacity. 

PMID- 25056214
TI  - Geomagnetic imprinting predicts spatio-temporal variation in homing migration of
      pink and sockeye salmon.
AB  - Animals navigate using a variety of sensory cues, but how each is weighted during
      different phases of movement (e.g. dispersal, foraging, homing) is controversial.
      Here, we examine the geomagnetic and olfactory imprinting hypotheses of natal
      homing with datasets that recorded variation in the migratory routes of sockeye
      (Oncorhynchus nerka) and pink (Oncorhynchus gorbuscha) salmon returning from the
      Pacific Ocean to the Fraser River, British Columbia. Drift of the magnetic field
      (i.e. geomagnetic imprinting) uniquely accounted for 23.2% and 44.0% of the
      variation in migration routes for sockeye and pink salmon, respectively. Ocean
      circulation (i.e. olfactory imprinting) predicted 6.1% and 0.1% of the variation
      in sockeye and pink migration routes, respectively. Sea surface temperature (a
      variable influencing salmon distribution but not navigation, directly) accounted
      for 13.0% of the variation in sockeye migration but was unrelated to pink
      migration. These findings suggest that geomagnetic navigation plays an important
      role in long-distance homing in salmon and that consideration of navigation
      mechanisms can aid in the management of migratory fishes by better predicting
      movement patterns. Finally, given the diversity of animals that use the Earth's
      magnetic field for navigation, geomagnetic drift may provide a unifying
      explanation for spatio-temporal variation in the movement patterns of many
      species. 

PMID- 25056215
TI  - Walking in circles: a modelling approach.
AB  - Blindfolded or disoriented people have the tendency to walk in circles rather
      than on a straight line even if they wanted to. Here, we use a minimalistic
      walking model to examine this phenomenon. The bipedal spring-loaded inverted
      pendulum exhibits asymptotically stable gaits with centre of mass (CoM) dynamics
      and ground reaction forces similar to human walking in the sagittal plane. We
      extend this model into three dimensions, and show that stable walking patterns
      persist if the leg is aligned with respect to the body (here: CoM velocity)
      instead of a world reference frame. Further, we demonstrate that asymmetric leg
      configurations, which are common in humans, will typically lead to walking in
      circles. The diameter of these circles depends strongly on parameter
      configuration, but is in line with empirical data from human walkers. Simulation
      results suggest that walking radius and especially direction of rotation are
      highly dependent on leg configuration and walking velocity, which explains
      inconsistent veering behaviour in repeated trials in human data. Finally, we
      discuss the relation between findings in the model and implications for human
      walking. 

PMID- 25056216
TI  - Geckoprinting: assembly of microelectronic devices on unconventional surfaces by
      transfer printing with isolated gecko setal arrays.
AB  - Developing electronics in unconventional forms provides opportunities to expand
      the use of electronics in diverse applications including bio-integrated or
      implanted electronics. One of the key challenges lies in integrating
      semiconductor microdevices onto unconventional substrates without glue, high
      pressure or temperature that may cause damage to microdevices, substrates or
      interfaces. This paper describes a solution based on natural gecko setal arrays
      that switch adhesion mechanically on and off, enabling pick and place
      manipulation of thin microscale semiconductor materials onto diverse surfaces
      including plants and insects whose surfaces are usually rough and irregular. A
      demonstration of functional 'geckoprinted' microelectronic devices provides a
      proof of concept of our results in practical applications. 

PMID- 25056217
TI  - To react or not to react? Intrinsic stochasticity of human control in virtual
      stick balancing.
AB  - Understanding how humans control unstable systems is central to many research
      problems, with applications ranging from quiet standing to aircraft landing.
      Increasingly, much evidence appears in favour of event-driven control hypothesis:
      human operators only start actively controlling the system when the discrepancy
      between the current and desired system states becomes large enough. The event
      driven models based on the concept of threshold can explain many features of the
      experimentally observed dynamics. However, much still remains unclear about the
      dynamics of human-controlled systems, which likely indicates that humans use more
      intricate control mechanisms. This paper argues that control activation in humans
      may be not threshold-driven, but instead intrinsically stochastic, noise-driven.
      Specifically, we suggest that control activation stems from stochastic interplay
      between the operator's need to keep the controlled system near the goal state, on
      the one hand, and the tendency to postpone interrupting the system dynamics, on
      the other hand. We propose a model capturing this interplay and show that it
      matches the experimental data on human balancing of virtual overdamped stick. Our
      results illuminate that the noise-driven activation mechanism plays a crucial
      role at least in the considered task, and, hypothetically, in a broad range of
      human-controlled processes. 

PMID- 25056219
TI  - Macrophage migration inhibitory factor (MIF) in the stratum corneum: a marker of
      the local severity of atopic dermatitis.
AB  - Different biomarkers are used to evaluate the severity of atopic dermatitis (AD);
      however, it remains difficult to determine the severity of localized skin
      lesions. MIF plays an essential role in the pathophysiology of skin inflammation.
      To establish whether the MIF level in the stratum corneum (SC) serves as a marker
      of the severity of AD lesions, we examined the SC MIF (scMIF) levels in AD
      patients. The SC of the cheek, neck and upper arm skin was collected using tape
      stripping, and the scMIF levels were measured. Consequently, the scMIF levels
      were found to be significantly higher in the involved skin lesions than the
      uninvolved areas within the same patient. Moreover, the scMIF levels were
      significantly correlated with the severity of local skin lesions. These findings
      suggest that the scMIF level can be used as an effective marker for evaluating
      the local severity of AD. 

PMID- 25056220
TI  - Do medical students really need lecture handouts?

PMID- 25056221
TI  - Collective motion of cells: from experiments to models.
AB  - Swarming or collective motion of living entities is one of the most common and
      spectacular manifestations of living systems that have been extensively studied
      in recent years. A number of general principles have been established. The
      interactions at the level of cells are quite different from those among
      individual animals, therefore the study of collective motion of cells is likely
      to reveal some specific important features which we plan to overview in this
      paper. In addition to presenting the most appealing results from the quickly
      growing related literature we also deliver a critical discussion of the emerging
      picture and summarize our present understanding of collective motion at the
      cellular level. Collective motion of cells plays an essential role in a number of
      experimental and real-life situations. In most cases the coordinated motion is a
      helpful aspect of the given phenomenon and results in making a related process
      more efficient (e.g., embryogenesis or wound healing), while in the case of tumor
      cell invasion it appears to speed up the progression of the disease. In these
      mechanisms cells both have to be motile and adhere to one another, the adherence
      feature being the most specific to this sort of collective behavior. One of the
      central aims of this review is to present the related experimental observations
      and treat them in light of a few basic computational models so as to make an
      interpretation of the phenomena at a quantitative level as well. 

PMID- 25056222
TI  - Mechanisms involved in kinin-induced glioma cells proliferation: the role of
      ERK1/2 and PI3K/Akt pathways.
AB  - Gliomas are the most common malignant brain tumors in adults. Bradykinin (BK)
      displays an important role in cancer, although the exact role of kinin receptors
      in the glioma biology remains unclear. This study investigated the role of kinin
      B1 and B2 receptors (B1R and B2R) on cell proliferation in human glioblastoma
      cell lineages. The mRNA expression of B1R and B2R was verified by RT-qPCR,
      whereas the effects of kinin agonists (des-Arg(9)-BK and BK) were analyzed by
      cell counting, MTT assay and annexin-V/PI determination. The PI3K/Akt and ERK1/2
      signaling activation was assessed by flow cytometry. Our results demonstrated
      that both human glioblastoma cell lines U-138MG and U-251MG express functional
      B1R and B2R. The proliferative effects induced by the incubation of des-Arg(9)-BK
      and BK are likely related to the activation of PI3K/Akt and ERK 1/2 pathways.
      Moreover, the pre-incubation of the selective PI3Kgamma blocker AS252424 markedly
      prevented kinin-induced AKT phosphorylation. Noteworthy, the selective B1R and
      B2R antagonists SSR240612 and HOE-140 were able to induce cell death of either
      lineages, with mixed apoptosis/necrosis characteristics. Taken together, the
      present results show that activation of B1R and B2R might contribute to
      glioblastoma progression in vitro. Furthermore, PI3K/Akt and ERK 1/2 signaling
      may be a target for adjuvant treatment of glioblastoma with a possible impact on
      tumor proliferation. 

PMID- 25056223
TI  - Post-discharge suicides of inpatients with bipolar disorder in Finland.
AB  - OBJECTIVES: Suicide risk in psychiatric inpatients is known to be remarkably high
      after discharge. However, temporal patterns and risk factors among patients with
      bipolar disorder remain obscure. We investigated post-discharge temporal patterns
      of hazard and risk factors by type of illness phase among patients with bipolar
      disorder. METHODS: Based on national registers, all discharges of patients with
      bipolar disorder from a psychiatric ward in Finland in 1987-2003 (n = 52,747)
      were identified, and each patient was followed up to post-index discharge or to
      suicide (n = 466). For discharges occurring in 1995-2003 (n = 35,946), factors
      modifying hazard of suicide during the first 120 days (n = 129) were
      investigated. RESULTS: The temporal pattern of suicide risk depended on the type
      of illness phase, being highest but steeply declining after discharge with
      depression; less high and declining in mixed states; lower and relatively stable
      after mania. In Cox models, for post-discharge suicides (n = 65) after
      hospitalizations for bipolar depression (n = 9,635), the hazard ratio was 8.05 (p
      = 0.001) after hospitalization with a suicide attempt and 3.63 (p < 0.001) for
      male patients, but 0.186 (p = 0.001) for patients taking lithium. Suicides after
      mania (n = 28) or mixed episodes (n = 20) were predicted by male sex and
      preceding suicide attempts, respectively. CONCLUSIONS: Among inpatients with
      bipolar disorder, suicide risk is high and related strongly to the time elapsed
      from discharge after hospitalizations for depressive episodes, and less strongly
      after hospitalizations for mixed episodes. Intra-episodic suicide attempts and
      male sex powerfully predict suicide risk. Lower suicide rate after
      hospitalizations for depression among patients prescribed lithium is consistent
      with a preventive effect.

PMID- 25056224
TI  - Fingertip dermatitis: occupational acrylate cross reaction.

PMID- 25056225
TI  - Dietary habits and prevalence of allergic rhinitis in 6 to 7-year-old
      schoolchildren in Turkey.
AB  - BACKGROUND: The prevalence of allergic rhinitis and other allergies has risen
      worldwide. Dietary habits are considered to be among the potential risk factors.
      The aim of this study was to evaluate the prevalence of allergic rhinitis and its
      relationship with dietary habits and other risk factors among 6 to 7-year-old
      Turkish schoolchildren. METHODS: In this cross-sectional study, a total of 11483
      children aged 6-7 years were surveyed. The prevalence of symptoms of allergic
      rhinitis was assessed using the ISAAC protocol. Dietary information was collected
      using a food frequency questionnaire. RESULTS: Of them, 9875 (50.7% M 49.3% F)
      questionnaires were appropriately completed. The prevalence rates of lifetime
      rhinitis, current rhinitis, current rhinoconjunctivitis and physician-diagnosed
      allergic rhinitis, were 44.3%, 29.2%, 8.5% and 8.1%, respectively. Consumption of
      rice, and cereals >=3 times per week showed protective effect on physician
      diagnosed allergic rhinitis (aOR = 0.53, 95% CI = 0.32-0.87 and aOR = 0.58, 95%
      CI = 0.36-0.92). Eating pasta, and chocolates >=3 times per week showed
      protective effect on current rhinoconjunctivitis (aOR = 0.45, 95% CI = 0.25-0.79
      and aOR = 0.50, 95% CI = 0.29-0.86). Eating lollipops, candies and animal fats
      >=3 times per week was positively associated with current rhinoconjunctivitis
      (aOR = 1.47, 95% CI = 1.00-2.17 and aOR = 2.25, 95% CI = 1.11-4.56). Protective
      effect of the Mediterranean diet was not significant. CONCLUSIONS: Frequent
      consumption of cereals, rice, pasta and chocolates may have beneficial effect on
      symptoms of rhinoconjunctivitis. Although dietary habits may affect the
      prevalence of symptoms of current rhinoconjunctivitis, the Mediterranean diet
      alone may not be protective against rhinoconjunctivitis.

PMID- 25056226
TI  - Effects of bifidobacterial supplementation to pregnant women and infants in the
      prevention of allergy development in infants and on fecal microbiota.
AB  - BACKGROUND: Probiotic administration may be a useful method for preventing
      allergies in infants; however, there have been controversial results about the
      efficacy. We investigated the effects of bifidobacterial supplementation on the
      risk of developing allergic diseases in the Japanese population. METHODS: In an
      open trial, we gave Bifidobacterium breve M-16V and Bifidobacterium longum BB536
      prenatally to 130 mothers beginning 1 month prior to delivery and postnatally to
      their infants for 6 months. Another 36 mother-infant pairs served as controls and
      did not receive the bifidobacterial supplementation. Development of allergic
      symptoms in the infants was assessed at 4, 10 and 18 months of age. Fecal samples
      were collected from the mothers and infants. RESULTS: The risk of developing
      eczema/atopic dermatitis (AD) during the first 18 months of life was
      significantly reduced in infants in the probiotic group (OR: 0.231 [95% CI: 0.084
      0.628] and 0.304 [0.105-0.892] at 10 and 18 months of age, respectively).
      Pyrosequencing analyses indicated an altered composition of the fecal microbiota
      at 4 months for infants who developed eczema/AD at 4 and 10 months of age. The
      proportion of Proteobacteria was significantly lower (P = 0.007) in mothers at
      the time of delivery who received the supplementation when compared with the
      control group and was positively correlated (r = 0.283, P = 0.024) with that of
      infants at 4 months of age. No adverse effects were related to the use of
      probiotics. CONCLUSIONS: These data suggest that the prenatal and postnatal
      supplementation of bifidobacteria is effective in primary preventing allergic
      diseases. Some limited changes in the composition of fecal microbiota by the
      bifidobacterial supplementation were observed.

PMID- 25056227
TI  - Efficacy and safety of fluticasone furoate nasal spray in Japanese children with
      perennial allergic rhinitis: a multicentre, randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Fluticasone furoate nasal spray (FFNS) is a glucocorticoid developed
      for the treatment of allergic rhinitis (AR). This is the first randomized
      clinical trial to assess the efficacy and safety of FFNS in Japanese children
      with perennial AR (PAR). METHODS: In this multicentre, randomized, double-blind,
      placebo-controlled, parallel-group, phase III study, 261 children aged 6 to <15
      years were treated with FFNS 55MUg, once daily or placebo for two weeks. Nasal
      and ocular symptoms were rated by parents/guardians/patients in the patient daily
      diary. The primary endpoint was the mean change from baseline in the three total
      nasal symptom score (3TNSS). In addition, rhinoscopic findings were rated by the
      investigators as an efficacy measure. As a safety measure, adverse events and
      clinical chemistry and hematology were evaluated. RESULTS: Mean change from
      baseline over the entire treatment period in 3TNSS was greater in the FFNS 55MUg
      group compared with placebo, and the difference was statistically significant (p
      < 0.001). Significant improvements in rhinoscopic findings of swelling of
      inferior turbinate mucosa and quantity of nasal discharge were also observed. The
      total ocular symptom score (TOSS) was reduced significantly in the FFNS 55MUg
      group, compared with placebo, in the second week in a subgroup of patients with
      baseline TOSS > 0. The incidence of adverse events was similar between FFNS
      55MUg(18%) and placebo (19%). CONCLUSIONS: Two-week treatment with FFNS 55MUg,
      once daily is effective and tolerable in Japanese children aged 6 to <15 years
      with PAR.

PMID- 25056228
TI  - Cellular responses to Staphylococcus aureus alpha-toxin in chronic rhinosinusitis
      with nasal polyps.
AB  - BACKGROUND: In contrast to Staphylococcus aureus-derived superantigenic
      exotoxins, the role of non-superantigenic exotoxins in the pathogenesis of
      eosinophilic airway diseases remains obscure. We sought to characterize S. aureus
      alpha-toxin-induced cellular responses in chronic rhinosinusitis with nasal
      polyps (CRSwNP). METHODS: Dispersed nasal polyp cells and uncinate tissue cells
      were prepared from patients with CRS with and without nasal polyps, respectively.
      Cells were incubated with various concentrations of alpha-toxin or staphylococcal
      enterotoxin B and then the levels of IL-5, IL-13, IFN-gamma, IL-17A, and IL-10 in
      the cell supernatants were determined. The pathophysiological significance of
      alpha-toxin-induced cytokine production was also determined including
      radiological severity of rhinosinusitis, tissue and blood eosinophilia, serum
      total IgE level, and 1-s forced expiratory volume/forced vital capacity ratio
      (FEV1/FVC). RESULTS: Nasal polyp cells produced substantial amounts of IL-5, IL
      13, IFN-gamma, IL-17A, and IL-10 in response to alpha-toxin. Cytokine production
      was higher in nasal polyp cells than in uncinate tissue cells. The potency of
      alpha-toxin in stimulating IL-5, IL-13, and IL-10 production was comparable to
      that of enterotoxin. Alpha-toxin-induced IFN-gamma, IL-17A, and IL-10 production
      significantly and negatively correlated with the degree of eosinophil
      infiltration into nasal polyps. Conversely, alpha-toxin-induced IFN-gamma and IL
      10 production significantly and positively correlated with FEV1/FVC. IL-10
      production was significantly lower in asthmatic patients compared to non
      asthmatics CONCLUSIONS: S. aureus-derived alpha-toxin can provoke cellular
      responses in nasal polyps. These responses, especially failure to synthesize IL
      10, may play a role in the pathophysiology of CRSwNP.

PMID- 25056229
TI  - Factors impacting same-day cancellation of outpatient pediatric magnetic
      resonance imaging under anesthesia.
AB  - BACKGROUND: Studies of elective surgical procedures indicate that cancellation is
      common and preventable. Little is known about cancellation of anesthesia
      supported elective diagnostic imaging. OBJECTIVE: To describe the reasons for
      same-day cancellation of MRI studies performed under sedation or anesthesia and
      identify patient characteristics associated with cancellations. MATERIALS AND
      METHODS: This case-control study was carried out in a university-affiliated
      tertiary care children's hospital. Cases were defined as elective outpatient MRI
      studies booked under anesthesia that were cancelled after the patient had arrived
      in the radiology department in 2009. Matched controls were identified by
      selecting the same day and time 1 week before or after the cancelled case. Main
      outcome measures included demographics, MRI study characteristics, and social and
      medical factors. RESULTS: There were 111 outpatient anesthesia-supported MRI
      studies cancelled on the same day as the assessment (cancellation rate: 4.5%), of
      which 74.6% were related to family and patient factors, while 22% were related to
      system factors. Cancelled cases involved patients who lived in lower median
      income quintile neighborhoods compared to controls (2 vs. 3; P = 0.0007; odds
      ratio [OR] 3.81; 95% confidence interval [CI] 1.18-12.34). Those who traveled a
      greater median distance (in kilometers) were less likely to be cancelled (18.8
      vs. 27.1, P = 0.0035). Although cancelled patients had a lower mean number of
      total medical services (2.5 vs. 3.0; P = 0.03; OR = 0.78; 95% CI 0.62-0.98),
      current medical factors (past 12 months) did not impact cancellations.
      CONCLUSION: Same-day cancellations of anesthesia-supported MRI studies are not
      uncommon, and the main predictor of cancellation seems to be socioeconomic rather
      than medical.

PMID- 25056230
TI  - Implementation of a competency check-off in diagnostic fluoroscopy for radiology
      trainees: impact on reducing radiation for three common fluoroscopic exams in
      children.
AB  - BACKGROUND: Fluoroscopy is an important tool for diagnosis in the pediatric
      population, but it carries the risk of radiation exposure. Because radiology
      resident education and experience in the use of fluoroscopy equipment in children
      vary, we implemented an intervention to standardize fluoroscopy training.
      OBJECTIVE: The purpose of this study is to determine the impact of implementing a
      fluoroscopy competency check-off for radiology resident trainees aimed at
      decreasing radiation exposure in three common pediatric fluoroscopic studies.
      MATERIALS AND METHODS: A fluoroscopy competency check-off form was developed for
      radiology resident trainees performing pediatric procedures. Techniques used to
      limit radiation exposure for common pediatric radiologic studies were reviewed as
      part of the check-off process. Pediatric radiologists supervised each trainee
      until they demonstrated competence to independently perform three specified
      procedures. Radiation dose was recorded for the three procedures, upper GI (UGI),
      voiding cystourethrogram (VCUG) and oropharyngeal (OPM) exams, over 6 months
      preceding and 6 months following implementation of the competency check-off. The
      mean cumulative dose for each procedure was compared before and after
      implementation of competency check-off using a Kruskal-Wallis test. RESULTS:
      During the 12-month study period doses from 909 fluoroscopic procedures were
      recorded. In the 6 months preceding competency check-off implementation,
      procedures were performed by 24 radiology resident trainees including 171 UGI,
      176 VCUG and 171 OPM exams. In the 6 months following competency check-off, 23
      trainees performed 114 UGI, 145 VCUG and 132 OPM exams. After competency check
      off implementation, a statistically significant reduction in average radiation
      dose was found for all three studies (P < 0.001). Median cumulative doses (mGy)
      were decreased by 33%, 36% and 13% for UGIs, VCUGs and OPMs, respectively.
      CONCLUSION: Implementation of a competency check-off for radiology resident
      trainees can reduce average radiation doses in pediatric patients undergoing
      three common fluoroscopic studies.

PMID- 25056231
TI  - Stereoselective skin anti-photoaging properties of ginsenoside Rg3 in UV-B
      irradiated keratinocytes.
AB  - Ginsenosides are major bioactive constituents that are responsible for the
      diverse pharmacological activities of ginseng. This work aimed to assess the skin
      anti-photoaging activities of the two stereoisomeric forms of ginsenoside Rg3,
      20(S)-Rg3 and 20(R)-Rg3. When the two Rg3 stereoisomers were added to cultured
      human keratinocyte HaCaT cells prior to irradiation with 70 mJ/cm(2) UV-B, 20(S)
      Rg3, but not 20(R)-Rg3, decreased the UV-B-induced intracellular reactive oxygen
      species (ROS) levels in a concentration-dependent manner, as detected by both
      fluorometric and confocal microscopic analyses. Likewise, 20(S)-Rg3, but not
      20(R)-Rg3, decreased the UV-B-induced ROS levels in human dermal fibroblast
      cells. Both stereoisomers were unable to modulate the nitric oxide levels in
      HaCaT cells under UV-B irradiation, and induced no cytotoxicity in cultured
      keratinocytes and fibroblasts. 20(S)-Rg3 suppressed the UV-B-induced matrix
      metalloproteinase (MMP)-2 activities in HaCaT cells. Taken together, these
      results indicate that 20(S)-Rg3 possesses both ROS-scavenging and MMP-2
      inhibitory activities, while 20(R)-Rg3 possesses neither activity. These findings
      imply that ginsenoside Rg3 stereoselectively demonstrates skin anti-photoaging
      activities.

PMID- 25056232
TI  - Hydroxysafflor yellow a attenuates small airway remodeling in a rat model of
      chronic obstructive pulmonary disease.
AB  - Our previous studies found that hydroxysafflor yellow A (HSYA), an active
      ingredient in Carthamus tinctorius L., has anti-inflammatory and anti-fibrosis
      properties. In this study, we investigated the effect of HSYA on small airway
      remodeling (SAR) in a chronic obstructive pulmonary disease (COPD) rat model
      induced by cigarette smoke and lipopolysaccharide (LPS). SAR is a common lesion
      in COPD characterized by thickening of the airway wall, mainly by subepithelial
      fibrosis. In this study the thickness of the small airway was determined by total
      wall area/basement membrane perimeter (WAt/Pbm). Collagen deposition of the small
      airway was assessed by Masson's trichrome staining. HSYA significantly attenuated
      the thickening and collagen deposition of the small airway and inhibited
      transforming growth factor beta1 (TGF-beta1) mRNA and protein expression in COPD
      rat. In addition, HSYA inhibited the phosphorylation of p38 mitogen-activated
      protein kinases (MAPK) in the lung tissue of rat. HSYA can attenuate
      experimentally induced airway remodeling and this attenuation may be attributed
      to suppression of TGF-beta1 expression. 

PMID- 25056233
TI  - Single-anastomosis gastric bypass (SAGB): appraisal of clinical evidence.
AB  - Single-anastomosis (mini-) gastric bypass (SAGB) was proposed by Dr. Robert
      Rutledge. Criticism and prejudice against this procedure was raised by surgeons
      who preferred a more difficult procedure, laparoscopic Roux-en-Y gastric bypass
      (RYGB). Increasing data indicates the procedure is an effective and durable
      bariatric procedure. SAGB has lower operation risks compared to RYGB. The weight
      loss is better after SAGB because of a greater malabsorptive component than RYGB,
      but SAGB had a higher incidence of micronutrient deficiencies. Randomized
      controlled trial and long-term data demonstrate that SAGB can be regarded as a
      simpler and safer alternative to RYGB. We propose this procedure to be renamed
      "single-anastomosis gastric bypass (SAGB)" because the key feature of SAGB is the
      "single anastomosis" compared with the two anastomoses of RYGB.

PMID- 25056234
TI  - Discharge disposition after bariatric surgery.
AB  - Weight loss continues for extended time post-bariatric surgery; thus, discharge
      destination is an important factor to consider when examining outcomes of
      surgery. The Agency for Healthcare Research and Quality State Inpatient Database
      was utilized to identify patients with bariatric surgery and to determine factors
      associated with and predictive of home discharge. Patients that were discharged
      home had shorter length of stays, lower total hospital costs, fewer chronic
      conditions, and lower readmission rates. Factors predictive of discharge were
      identified. Being discharged home could be associated with characteristics vital
      to patient's long-term weight loss. It is imperative to focus on factors
      predictive of home discharge in order to reap the most beneficial outcomes of
      surgery. 

PMID- 25056235
TI  - The long and narrow gastric pouch for laparoscopic Roux-en-Y gastric bypass.

PMID- 25056237
TI  - The multilevel determinants of workers' mental health: results from the SALVEO
      study.
AB  - PURPOSE: This study examined the contribution of work, non-work and individual
      factors on workers' symptoms of psychological distress, depression and emotional
      exhaustion based on the multilevel determinants of workers' mental health model.
      METHODS: Data from the SALVEO Study were collected in 2009-2012 from a sample of
      1,954 employees nested in 63 workplaces in the province of Quebec (Canada).
      Multilevel regression models were used to analyse the data. RESULTS: Altogether,
      variables explain 32.2 % of psychological distress, 48.4 % of depression and 48.8
      % of emotional exhaustion. Mental health outcomes varied slightly between
      workplaces and skill utilisation, physical and psychological demands, abusive
      supervision, interpersonal conflicts and job insecurity are related to the
      outcomes. Living in couple, having young children at home, family-to-work
      conflict, work-to-family conflict, strained marital and parental relations, and
      social support outside the workplace associated with the outcomes. Most of the
      individual characteristics also correlated with the three outcomes. Importantly,
      non-work and individual factors modulated the number and type of work factors
      related to the three outcomes. CONCLUSION: The results of this study suggest
      expanding perspectives on occupational mental health that fully recognise the
      complexity of workers' mental health determinants.

PMID- 25056238
TI  - Morbidity profile of first-degree relatives of probands with schizophrenia: a
      comparison with mood disorder and healthy control.
AB  - PURPOSE: There is a paucity of data on heritability of psychotic disorders in
      Africa. The study aimed to investigate morbid risk of schizophrenia and mood
      disorder among first-degree relatives of schizophrenia probands, compared with
      mood disorder and healthy controls. METHODS: The study examined 330 first-degree
      relatives of probands with schizophrenia (n = 50), 350 first-degree relatives of
      probands with mood disorder (n = 50) and 387 first-degree relatives of healthy
      control (n = 50). The Schedules for Clinical Assessment in Neuropsychiatry, SCAN
      was used to ascertain diagnosis in ill subjects. To each subject, a socio
      demographic questionnaire was administered. Family history was obtained using the
      Family History Schedule. Morbid risk estimates were calculated using the Weinberg
      shorter method. RESULTS: There was a significant difference between the mean age
      of relatives of schizophrenia probands compared to mood disorder (p = 0.01, 95 %
      CI 1.34-9.61) and healthy control (p < 0.01, 95 % CI 1.53-9.84). There were also
      significant differences between the number of children of schizophrenia probands
      and the number of children of normal control (p < 0.01, 95 % CI -2.0 to -3.9), as
      well as the number of deceased first-degree relatives of schizophrenia probands
      compared to normal control (p = 0.04, 95 % CI 0.01-0.94). Finally, there was a
      significant difference between the number of first-degree relatives of
      schizophrenia probands compared to the number of first-degree relatives of
      healthy control who were below the age of risk for schizophrenia (p = 0.01, 95 %
      CI -0.12 to -1.27). Morbid risks of 4.38 and 0.39 were obtained for schizophrenia
      among first-degree relatives of probands with schizophrenia and mood disorder,
      while first-degree relatives of probands with schizophrenia, mood disorder and
      healthy control had morbid risks for mood disorder of 0.42, 3.82 and 0.35,
      respectively. CONCLUSION: The study revealed excess mortality among first-degree
      relatives of schizophrenia patients. First-degree relatives of probands with
      schizophrenia and mood disorder also had higher morbid risks for these psychotic
      conditions than healthy control with some measure of overlap between the two
      diagnostic categories.

PMID- 25056236
TI  - Perceived risk of relapse and role of medication: comparison between patients
      with psychosis and their caregivers.
AB  - PURPOSE: Studies have suggested that appraisal of relapse risk and knowledge of
      medications in relapse prevention may shape one's reactions towards an illness
      and treatment, and influence the illness outcome. The aim of this study is to
      explore patients' and caregivers' knowledge of medications, perceived chances of
      relapse and its predictors, as well as their relations with medication adherence.
      METHODS: Eighty patient-caregiver dyads participated in the study. Their
      knowledge about psychosis, specific knowledge about medications and course of
      illness of their own and their relatives, medication adherence and symptomatology
      of patients were assessed. Differences in knowledge between patients and
      caregivers were compared. The link between adherence with perceived relapse risk
      and consequences of stopping medication were explored. Multinomial regression
      analyses were performed to examine predictors of perceived relapse risk. RESULTS:
      More patients underestimated their chance of relapse and were unaware that
      stopping medication may lead to relapse. The lack of understanding about the
      effect of stopping medication of both caregivers and patients was related to poor
      medication adherence of patients. Patients perceived of having higher chance of
      relapse had more severe positive symptoms. Positive symptoms of patients and
      greater knowledge about psychosis of caregivers were related to higher
      caregivers' perceived relapse risk of their relative. CONCLUSIONS: This study
      explored the views of patients and their caregivers on the perceived risk of
      relapse and role of medication in preventing relapse, and the potential
      significance. Specific interventions addressing these areas should be considered
      in developing relapse prevention programs.

PMID- 25056239
TI  - What about doctors? The impact of medical errors.
AB  - Medical error is a distressing event to the patient and the health care
      providers. The impact of such events has been well studied on patients but poorly
      on health professionals. These events are still considered as a taboo in the
      medical culture and hence missed as great learning opportunities. They have
      negative impact on doctors' emotional wellbeing, general quality of life, and
      their professional practice and conduct. Medical errors and adverse events also
      affect the quality and cost of the health service. Health service administrations
      should provide healthcare professionals involved in such events with professional
      support and counselling services, and should consider and treat them as second
      victims. 

PMID- 25056240
TI  - Comparison of manual and suction pump aspiration techniques for performing
      bronchoalveolar lavage in 18 dogs with respiratory tract disease.
AB  - BACKGROUND: Different aspiration techniques to retrieve bronchoalveolar lavage
      fluid (BALF) affect sample quality in healthy dogs. Studies evaluating these
      techniques in dogs with respiratory disease are lacking. OBJECTIVES: To compare
      sample quality of BALF acquired by manual aspiration (MA) and suction pump
      aspiration (SPA). ANIMALS: Eighteen client-owned dogs with respiratory disease.
      METHODS: Randomized, blinded prospective clinical trial. Manual aspiration was
      performed with a 35-mL syringe attached directly to the bronchoscope biopsy
      channel and SPA was performed with a maximum of 50 mmHg negative pressure applied
      to the bronchoscope suction valve using the suction trap connection. Both
      aspiration techniques were performed in each dog on contralateral lung lobes,
      utilizing 2 mL/kg lavage volumes per site. Samples of BALF were analyzed by
      percentage of retrieved infusate, total nucleated cell count (TNCC), differential
      cell count, semiquantitative assessment of slide quality, and diagnosis score.
      Data were compared by paired Student's t-test, Wilcoxon signed-rank test, chi
      squared test, and ANOVA. Cohen's kappa coefficient was used to assess agreement.
      RESULTS: The percentage of retrieved BALF (P = .001) was significantly higher for
      SPA than MA. Substantial agreement was found between cytologic classification of
      BALF obtained with MA and SPA (kappa = 0.615). There was no significant
      difference in rate of definitive diagnosis achieved with cytologic assessment
      between techniques (P = .78). CONCLUSIONS AND CLINICAL IMPORTANCE: Suction pump
      aspiration, compared to MA, improved BALF retrieval, but did not significantly
      affect the rate of diagnostic success of bronchoalveolar lavage (BAL) in dogs
      with pulmonary disease.

PMID- 25056241
TI  - A retrospective study of prognostic factors in patients with interstitial
      pneumonia receiving long-term oxygen therapy.
AB  - PURPOSE: We retrospectively analyzed patients with clinically diagnosed
      interstitial pneumonia to investigate the factors which contribute to the
      difference in prognosis from the initiation of long-term oxygen therapy (LTOT)
      among subtypes. METHODS: Seventy-six patients with clinically diagnosed
      idiopathic interstitial pneumonia (IIP; n = 49) or interstitial pneumonia
      associated with collagen vascular disease (CVD-IP; n = 27) in whom LTOT was
      initiated in our facility from January 1999 to December 2012 were analyzed.
      RESULTS: Patients with CVD-IP had significantly longer survival time from the
      initiation of LTOT than those with IIP with the median survival of 51.7 months
      versus 18.8 months, respectively. The 1-year survival rate was 92.4% for patients
      with CVD-IP versus 76.5% for those with IIP, and 2-year survival was 88.6 versus
      36.0%, respectively. The patterns classified with high-resolution computed
      tomography (HRCT) were not associated with prognosis. The association between
      pulmonary hypertension and prognosis was unclear. In results of the multivariate
      Cox analysis which included factors demonstrating p < 0.1 in the univariate Cox
      analysis, male gender, low body mass index, and the absence of collagen vascular
      disease (CVD) were significantly associated with poor prognosis. CONCLUSIONS:
      After the initiation of LTOT, patients with IIP had poor prognosis regardless of
      the patterns classified with HRCT, while those with CVD-IP survived longer. Male
      gender, low body mass index, and the absence of CVD were the independent negative
      prognostic factors in patients with interstitial pneumonia receiving LTOT.

PMID- 25056242
TI  - Loss of a 1.6 Mb chromosome in Pyricularia oryzae harboring two alleles of AvrPik
      leads to acquisition of virulence to rice cultivars containing resistance alleles
      at the Pik locus.
AB  - A small and extra chromosome of 1.6 Mb was previously identified in a Pyricularia
      oryzae strain, 84R-62B. To understand a role of the 1.6 Mb chromosome in the
      pathogenic changeability of P. oryzae, we performed experiments designed to
      characterize the 1.6 Mb chromosome in the present study. A gene family encoding
      secreted protein Pex31s in P. oryzae consists of five homologs, Pex31-A to -E.
      Among them, Pex31-A and -D are known to be recognized by Pik-m and Pik/Pik-m/Pik
      p, respectively. In the present study, we identified Pex31-A and -D in the genome
      of 84R-62B. Segregation analyses using an F1 population between 84R-62B and
      another rice blast strain, Y93-245c-2, revealed a strong linkage between the two
      homologs and the 1.6 Mb chromosome of 84R-62B. A CHEF-Southern analysis revealed
      an association between the 1.6 Mb chromosome and the homologs, indicating that
      both homologs are located on the 1.6 Mb chromosome of 84R-62B. The loss of the
      1.6 Mb chromosome was observed in subcultures of a F1 progeny, F1-327. These
      subcultures concomitantly acquired virulence on Pik, Pik-m, and Pik-p. The
      present study is the first report showing that loss of a small and extra
      chromosome leads to pathogenic mutation of P. oryzae and may provide a new
      insight into the mechanisms generating pathogenic variation of this fungus.

PMID- 25056243
TI  - Helicobacter pylori infection and dementia: can actual data reinforce the
      hypothesis of a causal association?
AB  - Helicobacter pylori (H. pylori) is involved in the development of several
      gastroduodenal diseases. Since the latest decade, several studies have reported
      on the link between chronic H. pylori infection and a variety of extragastric
      manifestations, including dementia. To identify the publications on the
      association between H. pylori and dementia, a MEDLINE search was conducted.
      Although case-control studies reported controversial data, a recent longitudinal
      population-based cohort study found that after 20 years of follow-up, 28.9% of H.
      pylori-positive versus 21.1% of H. pylori-negative subjects developed dementia.
      After correction for confounding factors, the infection was significantly
      associated with higher risk of developing dementia (P=0.04). Moreover, in another
      study evaluating the effect of H. pylori eradication on the progression of
      dementia in Alzheimer's disease patients with peptic ulcer, the cure of the
      bacterium was associated with a decreased risk of dementia progression compared
      to persistent infection. To date, defining H. pylori as a target for prevention
      or treatment of dementia remains a topic with much controversy but of essence, as
      any relationship would reduce, due to the cost-effectiveness of the therapy, a
      burden on the National Health Care budget. The need for extensive studies with
      appropriate epidemiological and clinical approaches is crucial to investigate a
      potential causal relationship. 

PMID- 25056244
TI  - Relationships between osteoprotegerin, receptor activator of the nuclear factor
      kB ligand and serum levels and carotid intima-media thickness in patients with
      type 2 diabetes mellitus.
AB  - AIM: The aim of this paper was to investigate the association of circulating
      osteoprotegerin (OPG) and receptor activator of the nuclear factor kB ligand
      (RANKL) levels with carotid intima-media thickness (CIMT) in type 2 diabetes
      mellitus (T2DM). METHODS: We performed a cross-sectional community-based study
      including 40 T2DM postmenopausal women and 40 healthy controls. CIMT was measured
      by B-mode ultrasound. Serum OPG and RANKL were measured by solid-phase enzyme
      linked immunosorbent assay (ELISA). RESULTS: Serum OPG levels were higher in T2DM
      than in controls (median 2.9 vs 2.0 pmol/liter; P<0.001), significantly
      associated with CIMT in T2DM (P<0.001). RANKL levels were lower in T2DM than in
      controls (median 0.45 vs 0.60 pmol/liter; P<0.0001), however no association was
      found with CIMT. Serum OPG levels were associated with cross-sectional measure of
      CIMT in T2DM. CONCLUSION: The data would support the role of an increased
      OPG/RANKL ratio as a possible marker of progression of vascular dysfunction in
      diabetes.

PMID- 25056245
TI  - Combined oral contraceptives: health benefits beyond contraception.
AB  - It has been recognized for over 50 years that combined oral contraceptives (COCs)
      are also capable of offering health benefits beyond contraception through the
      treatment and prevention of several gynaecological and medical disorders. During
      the last years a constant attention was given to the adverse effects of COCs,
      whereas their non-contraceptive benefits were underestimated. To date, most women
      are still unaware of the therapeutic uses of hormonal contraceptives, while on
      the contrary there is an extensive and constantly increasing of these non
      contraceptive health benefits. This review summarizes the conditions of special
      interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism
      (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts,
      endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone
      mineral density, benign breast disease and endometrial/ovarian and colorectal
      cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis,
      menstrual migraine and in perimenopause have also been treated for more
      comprehensive information. Using COCs specifically for non-contraceptive
      indications is still outside the product licence in the majority of cases. We
      strongly believe that these aspects are not of minor relevance and they deserve a
      special consideration by health providers and by the mass media, which have the
      main responsibility in the diffusion of scientific information. Thus, counseling
      and education are necessary to help women make well-informed health-care
      decisions and it is also crucial to increase awareness among general
      practitioners and gynaecologists. 

PMID- 25056246
TI  - Catalysis by metal-organic frameworks in water.
AB  - Metal-organic frameworks (MOFs) having a large surface area and porosity as well
      as a high density of transition metals are increasingly used as heterogeneous
      catalysts for organic reactions. However, one of the main limitations of various
      MOFs has been their lack of structural stability that led to an assumption that
      MOFs are unstable materials, particularly in water or polar solvents. However,
      since a few years ago the hydrothermal stability of several MOFs such as MIL
      101(Cr), MIL-53(Al) and ZIF-8 has been demonstrated and, hence, they can be used
      as solid catalysts in the aqueous phase. The present review is aimed at showing
      that there are a sufficiently large number of reports proving that certain MOFs
      can be used as reusable catalysts in water as the solvent. The use of water as
      the solvent has considerable advantages from the environmental point of view and
      affordability. Water can be the solvent of choice for hydrolytic processes, but
      MOFs have been reported as catalysts in water even for esterifications and C-C
      couplings. Considering that the synthesis of new MOFs is an active area of
      research and the flexibility in the selection of transition metals and organic
      linkers, these materials can be prepared with the required
      hydrophilicity/hydrophobicity to adapt specifically for catalysis in aqueous
      phase. 

PMID- 25056247
TI  - Molecular dynamics simulations of ion solvation by flexible-boundary QM/MM: on
      the-fly partial charge transfer between QM and MM subsystems.
AB  - The flexible-boundary (FB) quantum mechanical/molecular mechanical (QM/MM) scheme
      accounts for partial charge transfer between the QM and MM subsystems. Previous
      calculations have demonstrated excellent performance of FB-QM/MM in geometry
      optimizations. This article reports an implementation to extend FB-QM/MM to
      molecular dynamics simulations. To prevent atoms from getting unreasonably close,
      which can lead to polarization catastrophe, empirical correcting functions are
      introduced to provide additive penalty energies for the involved atom pairs and
      to improve the descriptions of the repulsive exchange forces in FB-QM/MM
      calculations. Test calculations are carried out for chloride, lithium, sodium,
      and ammonium ions solvated in water. Comparisons with conventional QM/MM
      calculations suggest that the FB treatment provides reasonably good results for
      the charge distributions of the atoms in the QM subsystems and for the solvation
      shell structural properties, albeit smaller QM subsystems have been used in the
      FB-QM/MM dynamics simulations.

PMID- 25056248
TI  - Spectrum of phenotypic anomalies in four families with deletion of the SHOX
      enhancer region.
AB  - BACKGROUND: SHOX alterations have been reported in 67% of patients affected by
      Leri-Weill dyschondrosteosis (LWD), with a larger prevalence of gene deletions
      than point mutations. It has been recently demonstrated that these deletions can
      involve the SHOX enhancer region, rather that the coding region, with variable
      phenotype of the affected patients.Here, we report a SHOX gene analysis carried
      out by MLPA in 14 LWD patients from 4 families with variable phenotype. CASE
      PRESENTATION: All patients presented a SHOX enhancer deletion. In particular, a
      patient with a severe bilateral Madelung deformity without short stature showed a
      homozygous alteration identical to the recently described 47.5 kb PAR1 deletion.
      Moreover, we identified, for the first time, in three related patients with a
      severe bilateral Madelung deformity, a smaller deletion than the 47.5 kb PAR1
      deletion encompassing the same enhancer region (ECR1/CNE7). CONCLUSIONS: Data
      reported in this study provide new information about the spectrum of phenotypic
      alterations showed by LWD patients with different deletions of the SHOX enhancer
      region.

PMID- 25056249
TI  - Phase II drugs that are currently in development for the treatment of cachexia.
AB  - INTRODUCTION: Cachexia is a syndrome presenting with progressive unintentional
      weight loss and wasting and weakness of skeletal muscle. Cachexia is prevalent in
      cancer and in chronic diseases including chronic obstructive pulmonary disease
      (COPD). AREAS COVERED: The authors searched trial registers for current Phase II
      clinical trials on cachexia. Twelve studies were found with 11 compounds,
      including the anti-inflammatory drugs thalidomide, OHR/AVR118, celecoxib, VT-122,
      omega-3 supplements, and anabolic agents such as ghrelin analogues, MT-102,
      BYM338 and ruxolotinib. The authors note that one of the studies related to COPD
      while the others were related to different cancers. Herein, the authors describe
      the mechanisms of action and their Phase II study design. EXPERT OPINION: The
      compounds under study affect several pathways involved in cachexia by modulating
      inflammatory activity, anabolic potential, digestion and direct interaction with
      the muscle. Due to the multifactorial aspects of cachexia syndrome, combinations
      of these new drugs with nutritional intervention is probably the most promising
      approach. Furthermore, future studies should include interventions in pre
      cachetic patients, as this stage might be more responsive to treatment. Future
      studies will benefit from well-defined end points and improved measures of
      cachexia, providing new insight into the disease. This insight, in combination
      with the elucidation of cachexia's underlying mechanism, will yield new treatment
      strategies in the near future.

PMID- 25056250
TI  - Investigation of antibacterial effect of Cadmium Oxide nanoparticles on
      Staphylococcus Aureus bacteria.
AB  - BACKGROUND: Inorganic antibacterial factors provide high bacterial resistance and
      thermal stability. Inorganic nanomaterial consists of modern formulation,
      biological, chemical, and physical properties produced on the basis of their
      function and influenced by their nano scales, the reason for which they have
      become very popular. The antibacterial effect of Cadmium Oxide Nanoparticles on
      Staphylococcus Aureus has been studied for the first time in this research
      because of their resistance to antibiotics. MATERIALS AND METHODS: Different
      concentrations consist of 10 MUg/ml, 15 MUg/ml, and 20 MUg/ml have been provided
      and their effects were studied in the agar and broth against the foregoing
      bacteria. Needless to say, the optimization of their non-microbial effect in
      variable times, pH, and temperatures of exposure was analyzed. RESULTS: The
      results represented that there is a direct association between the nanoparticles
      applied dosage and the restrain effect augmentation of applied dosage results in
      increase in restrain effect. In the study of environmental factors (pH and
      temperature), the results are in line with the inherent physiology of the
      bacteria; however, there was a significant decline in the number of analyzed
      bacteria cells due to the "Double Effect" of nanoparticle-pH variations as well
      as nanoparticle-temperature variables. In the very study, the promotion of
      Cadmium Oxide nanoparticles concentration leads to the elevation of antimicrobial
      feature and the reduction of bacteria growth rate is consistent with the other
      surveys about the nanoparticles effects on microorganisms to be more specific,
      one can come to this conclusion that the presence of nanoparticles prompts
      cellular destruction. CONCLUSION: In the recent study, by elevation in Cadmium
      Oxide nanoparticles concentration, the antimicrobial property augments and the
      bacteria growth rate declines, that are in line with other researches about the
      nanoparticles effect on microorganisms.

PMID- 25056251
TI  - Cold agglutinin activity in 2 dogs.
AB  - A 5-year-old neutered male Mastiff and an 8-year-old spayed female Labrador
      Retriever were presented to the University of Minnesota Veterinary Medical
      Center. The Mastiff was presented for evaluation of lameness and pyoderma one
      month prior in Missouri, where he tested positive for Ehrlichia canis by serum
      ELISA test, treated with doxycycline. PCR for Ehrlichia sp, Anaplasma sp, Babesia
      sp, and Bartonella sp, and PCR for antigen receptor rearrangement were negative,
      serum protein electrophoresis (SPE) revealed polyclonal gammopathy, and mildly
      reactive lymphoid cells were seen cytologically. The Labrador presented with a
      proliferative rostral mandibular gingival mass and lipomas for further
      presurgical evaluation of cold agglutinin activity documented by a commercial
      laboratory 2 years earlier prior to removal of a grade II mast cell tumor. This
      dog had a negative SNAP4Dx, normal SPE, and persistently increased serum ALP
      activity and polyuria/polydipsia suggestive for hyperadrenocorticism. Both dogs
      had markedly agglutinated RBC in the EDTA samples that dispersed with warming,
      and normal plasma color. Cold agglutinin activity was demonstrated by direct
      saline agglutination testing using whole blood and washed erythrocytes
      demonstrating agglutination at 30 degrees C, 25 degrees C, 15 degrees C, and 4
      degrees C, but not at 37 degrees C. CBC results (ADVIA 2120i) from the Mastiff
      revealed no significant differences in the RBC results obtained at room
      temperature (RT) and at 37 degrees C; however, the RT run demonstrated negative
      bias in neutrophil and platelet concentrations attributed to rapid RBC settling.
      This uncommon hematologic condition may cause artifacts on the automated
      leukogram and platelet count, and may be subclinical for long periods. 

PMID- 25056252
TI  - Agent consumption with the Zeus(r) in the automated closed circuit anesthesia
      mode with O2/air mixtures.
AB  - BACKGROUND: Earlier software versions of the Zeus(r) (Lubeck, Drager, Germany)
      failed to provide true closed circuit anesthesia (CCA) conditions. We examined
      whether the latest software (SW 4.03 MK 04672-00) achieves this goal. METHODS: In
      8 ASA I-III patients, the CCA mode of the Zeus(r) was used to maintain the
      inspired O2 (FIO2) and end-expired sevoflurane % (FAsevo) at 50 and 1.8%,
      respectively. The fresh gas flow (FGF) of O2 and air and the sevoflurane
      injection rate (=Vinjsevo, mL liquid sevo/h) were videotaped from the control
      screen and entered offline into a spreadsheet. Cumulative sevoflurane usage
      during early wash-in (=0-1 min, CDsevo0-1), late wash-in (=1-5 min, CDsevo1-5),
      and maintenance (=5-60 min, CDsevo5-60) was calculated, and Vinjsevo between 1
      and 60 min was compared with published uptake data. RESULTS: FAsevo reached 1.8%
      within 101 (23) sec. CDsevo0-1 was between 1.24 (0.03) and 3.01(0.25) mL (a range
      is provided because no absolute Vinjsevo values were displayed once Vinjsevo was
      > 100 mL/h, which occurred between 15 +/- 2 and 46 +/- 6 sec). CDsevo1-5 was 0.81
      (0.37) mL, and CDsevo5-60 was 4.63 (0.94) mL. The Vinjsevo pattern between 1 and
      60 min matched previously published uptake data. Brief high FGF periods were used
      to maintain the target FIO2, and to refill the reservoir bag after external
      pressure had been applied to the abdomen; subsequent "spikes" wasted 0.08-0.19 mL
      and 0.14-0.49 mL sevoflurane (1-3% and 3-9% of total agent usage between 1 and 60
      min, respectively). CONCLUSION: Under the conditions specified, the Zeus(r)
      approaches CCA conditions so closely that further reductions in agent usage would
      have minimal economic significance.

PMID- 25056254
TI  - Young adults seeking medical care: do race and ethnicity matter?
AB  - KEY FINDINGS: Data from the National Health Interview Survey: 2008-2009. More
      than one-half of Hispanic young adults aged 20-29 years were uninsured in 2008
      2009 compared with one-third of non-Hispanic black young adults and almost one
      quarter of non-Hispanic white young adults. Among young adults aged 20-29 years,
      non-Hispanic white (66%) young adults were twice as likely as Hispanic (33%)
      young adults to have private health insurance coverage. Approximately equal
      percentages of Hispanic, non-Hispanic white, and non-Hispanic black young adults
      with private health insurance or Medicaid had a usual source of medical care.
      Uninsured non-Hispanic white (37%) and non-Hispanic black (33%) young adults were
      more likely to have unmet medical need than uninsured Hispanic (21%) young
      adults. Health care disparities among different racial and ethnic subgroups in
      the United States are of national concern. Health insurance is a key factor in
      the access to medical care services, and young adults in the United States aged
      20-29 years are more likely than adults aged 30 years and over to lack health
      insurance coverage (1-4). A previous report has examined the differences in
      health insurance and access to health care by gender among young adults aged 20
      29 years (5). This report focuses on the differences in health insurance and
      access to health care among Hispanic, non-Hispanic white, and non-Hispanic black
      young adults aged 20-29 years.

PMID- 25056253
TI  - Three-dimensional transesophageal echocardiography for descending aortic
      atheroma: a preliminary study.
AB  - Transesophageal echocardiography (TEE) is an efficient method for
      characterization of aortic atherosclerotic plaques (AAP). The aim of our study
      was to evaluate the feasibility and the additional contribution of three
      dimensional (3D) TEE in the evaluation of AAPs in descending thoracic aorta. We
      studied 82 patients referred for TEE regardless of the indication. All patients
      underwent two-dimensional (2D) conventional acquisitions. A 3D TEE study was
      performed for all AAPs localized in the descending thoracic aorta. Thickness,
      degree of calcification, the presence of ulceration or mobile debris were
      compared for 2D and 3D modes. From 3D data, three types of AAPs were defined
      according to their morphological characteristics (surface and contours). Among
      192 AAPs found on 2D acquisition, 189 (98.4 %) were also identified by 3D TEE.
      For AAP characterization, agreement was good between 2D TEE and 2D extracted from
      3D with the multiplanar reconstruction mode: 83.6 % (k = 0.69) for thickness and
      82.5 % (k = 0.72) for degree of calcification. All AAPs ulcerations (n = 13) and
      mobile debris (n = 3) seen in 2D were identified in 3D. 2D characteristics of the
      3D AAPs' morphological types were different: type I plaques were thin and rarely
      calcified; type III plaques were thicker and often calcified; and type II
      presented intermediate characteristics. There was overlap among groups and the 3D
      morphology could not be predicted from 2D data. 3D TEE is a feasible method for
      the analysis of AAPs. In addition to conventional characterization, 3D TEE
      provides a new morphological approach to AAPs.

PMID- 25056255
TI  - Copper(I)- and copper(0)-promoted homocoupling and homocoupling
      hydrodehalogenation reactions of dihalogenoclathrochelate precursors for C-C
      conjugated iron(II) bis-cage complexes.
AB  - Iron(II) dibromo- and diiodoclathrochelates undergo copper(I)-promoted reductive
      homocoupling in HMPA at 70-80  degrees C leading to C-C conjugated dibromo- and
      diiodo-bis-clathrochelates in high yields. Under the same conditions, their
      dichloroclathrochelate analog does not undergo the same homocoupling reaction, so
      the target dichloro-bis-cage product was obtained in high yield via dimerization
      of its heterodihalogenide iodochloromonomacrobicyclic precursor. The use of NMP
      as a solvent at 120-140  degrees C gave the mixture of bis-clathrochelates
      resulting from a tandem homocoupling-hydrodehalogenation reaction: the initial
      acetonitrile copper(I) solvato-complex at a high temperature underwent re
      solvatation and disproportionation leading to Cu(II) ions and nano-copper, which
      promoted the hydrodehalogenation process even at room temperature. The most
      probable pathway of this reaction in situ includes hydrodehalogenation of the
      already formed dihalogeno-bis-clathrochelate via the formation of reduced anion
      radical intermediates. As a result, chemical transformations of the iron(II)
      dihalogenoclathrochelates in the presence of an acetonitrile copper(I) solvato
      complex were found to depend both on the nature of halogen atoms in their ribbed
      chelate fragments and on reaction conditions (i.e. solvent and temperature). The
      C-C conjugated iron(II) dihalogeno-bis-clathrochelates easily undergo
      nucleophilic substitution with various N,S-nucleophiles giving ribbed
      functionalized bis-cage species. These iron(II) complexes were characterized by
      elemental analysis, MALDI-TOF mass spectrometry, IR, UV-Vis, (1)H and (13)C NMR
      spectroscopy, and by X-ray diffraction; their electrochemical properties were
      studied by cyclic voltammetry. The isomeric shift values in (57)Fe Mossbauer
      spectra of such cage compounds allowed identifying them as low-spin iron(II)
      complexes, while those of the quadrupole splitting are the evidence for a
      significant TP distortion of their FeN6-coordination polyhedra. As follows from
      CV data, the C-C conjugated iron(II) bis-clathrochelates undergo stepwise
      electrochemical reduction and oxidation giving mixed-valence Fe(II)Fe(I) and
      Fe(II)Fe(III) bis-cage intermediates.

PMID- 25056256
TI  - Pregnancy intentions among female sex workers: recognising their rights and wants
      as mothers.
AB  - OBJECTIVE: To better understand the prevalence and correlates of pregnancy
      intentions among female sex workers (FSWs). DESIGN: Cross-sectional analysis
      using data from an open prospective cohort of street and off-street FSWs in
      Vancouver, Canada, in partnership with local sex work and community agencies.
      METHODS: FSWs were recruited through outreach to street and off-street locations
      (e.g. massage parlours, micro-brothels) and completed interviewer-administered
      questionnaires and HIV/sexually transmitted infection testing. Bivariable and
      multivariable logistic regression was used to evaluate correlates of pregnancy
      intention, based on a 'yes' or 'no' response to the question "Are you planning on
      have any (any more) children in the future?". RESULTS: Of the 510 women, 394
      (77.3%) reported prior pregnancy, with 140 (27.5%) of the entire sample reporting
      positive pregnancy intentions. Regarding ethnicity, 35.3% were Caucasian and
      26.3% were Asian/visible minority, with no differences in pregnancy intention by
      ethnicity or HIV status; 38.4% reported Canadian Aboriginal ancestry. In our
      final multivariable model, servicing clients in formal indoor settings,
      inconsistent condom use by clients, younger age, and intimate partner violence
      (IPV) were associated with pregnancy intention. CONCLUSIONS: FSWs may have
      pregnancy intention levels similar to that of women in other occupations. Policy
      changes are needed to improve FSWs' access to integrated HIV and reproductive
      health services and harm reduction services, particularly for FSWs experiencing
      IPV.

PMID- 25056257
TI  - Role of intraoperative transesophageal echocardiography in detecting masked
      mitral regurgitation during left atrial myxoma surgery.
AB  - Myxomas are the most common type of cardiac tumor. Mobile or large left atrial
      (LA) myxomas frequently cause functional mitral stenosis, and can lead to mitral
      regurgitation (MR). Difficulties have been associated with detecting masked MR
      jets and evaluating the severity of MR during LA myxoma surgery due to the
      presence of a prolapsing tumor and changes in blood flow. We herein presented a
      case of LA myxoma with significant MR diagnosed on intraoperative transesophageal
      echocardiography (TEE) prior to cardiopulmonary bypass. Repeated careful
      observations on TEE led to a confident diagnosis of MR and the selection of an
      additional appropriate procedure. This case study highlighted the importance of
      intraoperative TEE in supporting clinical decision-making for optimal mitral
      valve procedures during LA myxoma surgery. 

PMID- 25056258
TI  - Anesthetic effects of propofol in the healthy human brain: functional imaging
      evidence.
AB  - Functional imaging methods, including positron emission tomography (PET) and
      functional magnetic resonance imaging (fMRI), have become important tools for
      studying how anesthetic drugs act in the human brain to induce the state of
      general anesthesia. Recent imaging studies using fMRI and PET techniques have
      demonstrated the regional effects of propofol on the brain. However, the
      pharmacological mechanism of the action of propofol in the intact human central
      nervous system is unclear. To explore the possible action targets of propofol in
      the human brain, a systematic review of the literature was performed. The
      literature search was performed with limiting factors of "propofol," "functional
      imaging," "positron emission tomography", and "functional magnetic resonance
      imaging" from 1966 to July 2013 (using Medline, EMBASE, CINAHL and hand searches
      of references). Studies meeting the inclusion criteria were reviewed and
      critiqued for the purpose of this literature research. Eighteen researches
      meeting the inclusion criteria were reviewed in terms of the appropriateness of
      valuation technique. In the unconscious state, propofol sharply reduces the
      regional glucose metabolism rate (rGMR) and regional cerebral blood flow (rCBF)
      in all brain regions, particularly in the thalamus. However, GMR, such as in the
      occipital, temporal, and frontal lobes, was obviously decreased at a sedative
      dosage of propofol, whereas, changes in the thalamus were not obvious. Using
      fMRI, several studies observed a decrease of connectivity of the thalamus versus
      an increase of connectivity within the pons of the brainstem during propofol
      induced mild sedation. During deep sedation, propofol preserves cortical sensory
      reactivity, the specific thalamocortical network is moderately affected, whereas
      the nonspecific thalamocortical network is severely suppressed. In contrast,
      several recent fMRI studies are consistent on the systemic decreased effects of
      propofol in the frontoparietal network. Accumulating evidence suggest that
      propofol-induced unconsciousness is associated with a global metabolic and
      vascular depression in the human brain and especially with a significant
      reduction in the thalamocortical network and the frontoparietal network. 

PMID- 25056259
TI  - Inflammation of the thoracolumbar fascia excites and sensitizes rat dorsal horn
      neurons.
AB  - BACKGROUND: Recent data show that the thoracolumbar fascia can be a source of
      pain. However, the spinal neuronal mechanisms underlying pain from a
      pathologically altered fascia are unknown. The present study aimed at finding out
      how dorsal horn neurons react to input from a chronically inflamed thoracolumbar
      fascia. METHODS: Recordings from rat dorsal horn neurons were made in the spinal
      segment L3. Twelve days before the recordings, the thoracolumbar fascia was
      inflamed by injection of complete Freund's adjuvant. Control animals received an
      injection of isotonic saline. In addition, behavioural experiments were carried
      out. RESULTS: Neurons in the spinal segment L3 do not normally receive input from
      the fascia, but 11.1% of the neurons did when the fascia was inflamed. Compared
      with control, the proportion of neurons having input from all deep somatic
      tissues rose from 10.8% to 33.3% (p < 0.02). Moreover, many neurons acquired new
      deep receptive fields, most of which were located in the hindlimb (p < 0.04).
      Surprisingly, the pressure pain threshold of the inflamed rats did not change,
      but they showed a reduction in exploratory activity. CONCLUSIONS: One of the
      prominent findings was the appearance of new receptive fields in deep tissues of
      the hindlimb. Together with the expansion of the spinal target region of fascia
      afferents into the segment L3, the appearance of new receptive fields is a
      possible explanation for the spread of pain in patients with non-specific low
      back pain.

PMID- 25056260
TI  - Re-evaluation of link between interpregnancy interval and adverse birth outcomes:
      retrospective cohort study matching two intervals per mother.
AB  - OBJECTIVE: To re-evaluate the causal effect of interpregnancy interval on adverse
      birth outcomes, on the basis that previous studies relying on between mother
      comparisons may have inadequately adjusted for confounding by maternal risk
      factors. DESIGN: Retrospective cohort study using conditional logistic regression
      (matching two intervals per mother so each mother acts as her own control) to
      model the incidence of adverse birth outcomes as a function of interpregnancy
      interval; additional unconditional logistic regression with adjustment for
      confounders enabled comparison with the unmatched design of previous studies.
      SETTING: Perth, Western Australia, 1980-2010. PARTICIPANTS: 40 441 mothers who
      each delivered three liveborn singleton neonates. MAIN OUTCOME MEASURES: Preterm
      birth (<37 weeks), small for gestational age birth (<10th centile of birth weight
      by sex and gestational age), and low birth weight (<2500 g). RESULTS: Within
      mother analysis of interpregnancy intervals indicated a much weaker effect of
      short intervals on the odds of preterm birth and low birth weight compared with
      estimates generated using a traditional between mother analysis. The traditional
      unmatched design estimated an adjusted odds ratio for an interpregnancy interval
      of 0-5 months (relative to the reference category of 18-23 months) of 1.41 (95%
      confidence interval 1.31 to 1.51) for preterm birth, 1.26 (1.15 to 1.37) for low
      birth weight, and 0.98 (0.92 to 1.06) for small for gestational age birth. In
      comparison, the matched design showed a much weaker effect of short
      interpregnancy interval on preterm birth (odds ratio 1.07, 0.86 to 1.34) and low
      birth weight (1.03, 0.79 to 1.34), and the effect for small for gestational age
      birth remained small (1.08, 0.87 to 1.34). Both the unmatched and matched models
      estimated a high odds of small for gestational age birth and low birth weight for
      long interpregnancy intervals (longer than 59 months), but the estimated effect
      of long interpregnancy intervals on the odds of preterm birth was much weaker in
      the matched model than in the unmatched model. CONCLUSION: This study questions
      the causal effect of short interpregnancy intervals on adverse birth outcomes and
      points to the possibility of unmeasured or inadequately specified maternal
      factors in previous studies.

PMID- 25056261
TI  - Spacing babies.

PMID- 25056262
TI  - Effect of Helicobacter pylori eradication on metachronous gastric cancer after
      endoscopic resection of gastric tumors: a meta-analysis.
AB  - BACKGROUND: Although endoscopic resection is widely accepted as the curative
      treatment modality for early gastric cancer, secondary metachronous cancer may
      subsequently develop in the residual gastric mucosa. The preventive effect of
      Helicobacter pylori eradication on the development of metachronous gastric cancer
      in such cases remains controversial. The aim of this study was to determine the
      effect of H. pylori eradication on the development of metachronous gastric cancer
      after endoscopic resection of gastric neoplasm by a meta-analysis of all relevant
      studies. MATERIALS AND METHODS: We performed a systematic literature search of
      PubMed, EMBASE, Google Scholar, and the Cochrane Library without language
      restrictions through March 31, 2014. We included all relevant articles, including
      prospective, observational, and retrospective studies. Pooled estimates (odds
      ratios with 95% confidence intervals) were obtained using a random effects model.
      RESULTS: Thirteen studies were considered to be appropriate for this meta
      analysis. Compared with the control group, the pooled odds ratio in the
      eradication group was 0.42 (95% confidence interval, 0.32-0.56), and there was no
      heterogeneity across the studies (p = .853, I(2) = 0%). Subgroup analysis of
      three prospective trials also showed a lower incidence of metachronous cancer in
      the eradication group (odds ratio, 0.39; 95% confidence interval, 0.20-0.75).
      There was no evidence of publication bias in this meta-analysis. CONCLUSION:
      Helicobacter pylori eradication reduces the occurrence of metachronous gastric
      cancer in patients who have undergone endoscopic resection.

PMID- 25056263
TI  - [Implantation of a Salto 2 total ankle prosthesis].
AB  - AIM OF SURGERY: Operative treatment of advanced primary and secondary arthritis
      of the ankle was carried out with the aim of achieving pain-free movement and
      retention of mobility. INDICATIONS: Surgery is indicated when conservative
      therapy is no longer sufficient for treatment of arthritis of the ankle with
      painful limited movement, sufficient bony joint conditions and correctable
      instability or axis malpositioning. CONTRAINDICATIONS: Surgery is not recommended
      with general surgical or anesthesiological contraindications, rampant infections,
      severe disturbances of peripheral perfusion, bony defects in areas relevant for
      anchoring, unstable soft tissue conditions, talus necrosis >30 %, manifest
      osteoporosis and severe non-correctable instability or malpositioning. OPERATION
      TECHNIQUE: Tibial and talar bone resection was carried out via ventral access to
      the ankle through an incision and if present, soft tissue correction of
      instability after insertion of test components. Cement-free implantation of the
      original implants followed by subtle reconstruction of the extensor retinaculum
      and layer for layer closure of the wound. ADDITIONAL INTERVENTIONS: Additional
      measures were necessary on the periarticular soft tissues, the hindfoot and lower
      leg due to movement restrictions, instability and axis malpositioning which could
      be carried out in a one or two stage procedure depending on the extent and
      morphology. RESULTS: Between February 2009 and February 2010 a total of 115
      patients (52 % with posttraumatic arthritis) received a cement-free implantation
      with a Salto 2 prosthesis. Additional corrective interventions were carried out
      in the presence of varus and valgus deformities. The degree of movement for
      dorsal extension and plantar flexion could be increased by an average of 8.3
      degrees . The interventions resulted in a significant reduction in pain from an
      average preoperative visual analogue pain scale (VAS) score of 7.8 (range 5-10)
      to an average postoperative score of 1.9 (range 0-6.1).

PMID- 25056264
TI  - [Arthroscopic posterior shoulder stabilization with an iliac bone graft and
      capsular repair].
AB  - OBJECTIVE: Arthroscopic posterior shoulder stabilization with an iliac bone graft
      and capsulolabral repair, which should combine the pre-existing open procedure
      with the advantages of improved arthroscopic visualization. INDICATIONS:
      Posterior instability with concomitant pathologies (e.g. capsular insufficiency,
      posterior Bankart lesion, posterior glenoid dysplasia) and recurrent posterior
      instability after failed soft tissue reconstruction. CONTRAINDICATIONS:
      Instability osteoarthritis, locked posterior shoulder dislocation, large reverse
      Hill-Sachs lesion, extended posterior defect of the glenoid. SURGICAL TECHNIQUE:
      After arthroscopic evaluation of the shoulder joint and treatment of concomitant
      pathologies, a tricortical bone graft is harvested from the iliac crest. The
      posterior capsule is arthroscopically detached from the labrum and the posterior
      deltoid and rotator cuff are split in line of the muscle fibers. Then the bone
      graft is positioned and fixed to the posterior scapular neck as an extension of
      the articular glenoid surface. Thereafter, capsular reconstruction is performed
      after insertion of suture anchors in the posterior glenoid rim. POSTOPERATIVE
      MANAGEMENT: During the first 6 weeks 60 degrees  of abduction and flexion are
      permitted without any rotation and full range of motion is developed gradually.
      Internal rotation is allowed after 8 weeks and return to sports after 12 weeks.
      RESULTS: For posterior shoulder instability 13 of these operations were performed
      in our hospital since 2011. Until now, no recurrent instability was observed.
      After remodelling of the graft, one patient complained about posterior soft
      tissue irritation so the screws were removed.

PMID- 25056265
TI  - Dabigatran, bleeding, and the regulators.

PMID- 25056266
TI  - Chemoselective phototransformation of C-H bonds on a polymer surface through a
      photoinduced cerium recycling redox reaction.
AB  - It is generally accepted that Ce(4+) is unable to directly oxidize unreactive
      alkyl C-H bonds without the assistance of adjacent polar groups. Herein, we
      demonstrate in our newly developed confined photochemical reaction system that
      this recognized issue may be challenged. As we found, when a thin layer of a
      CeCl(3)/HCl aqueous solution was applied to a polymeric substrate and the
      substrate subjected to UV irradiation, Ce(3+) was first photooxidized to form
      Ce(4+) in the presence of H(+), and the in situ formed Ce(4+) then performs an
      oxidation reaction on the C-H bonds of the polymer surface to form surface-carbon
      radicals for radical graft polymerization reactions and functional-group
      transformations, while reducing to Ce(3+) and releasing H(+) in the process. This
      photoinduced cerium recycling redox (PCRR) reaction behaved as a biomimetic
      system in an artificial recycling reaction, leading to a sustainable chemical
      modification strategy for directly transforming alkyl C-H bonds on polymer
      surfaces into small-molecule groups and polymer brushes. This method is expected
      to provide a green and economical tool for industrial applications of polymer
      surface modification.

PMID- 25056267
TI  - Plasmonic activation of a fluorescent carbazole-oxazine switch.
AB  - The covalent attachment of a carbazole fluorophore to an oxazine photochrome
      permits the reversible activation of fluorescence under optical control.
      Ultraviolet irradiation with a pulsed laser opens the oxazine ring to shift
      bathochromically the absorption of the carbazole component. Concomitant visible
      illumination excites selectively the carbazole fluorophore of the photochemical
      product to produce fluorescence. The photogenerated and fluorescent species
      reverts spontaneously on a submicrosecond timescale to the initial nonemissive
      state of the carbazole-oxazine dyad. The photochemical and photophysical
      properties engineered into this particular molecular switch allow the convenient
      monitoring of plasmonic effects on photochemical reactions with fluorescence
      measurements. In close proximity to silver nanoparticles, visible illumination
      with a continuous-wave laser also results in fluorescence activation. The
      metallic nanostructures enable the two-photon excitation of the oxazine component
      to induce the photochromic transformation and then facilitate the one-photon
      excitation of the photochemical product to generate fluorescence. Thus, these
      operating principles offer the opportunity to avoid altogether the need of pulsed
      ultraviolet irradiation to trigger the photochromic transformation and, instead,
      allow fluorescence activation with a single visible source operating at low
      illumination power. 

PMID- 25056268
TI  - Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPRs) and their
      associated cas genes serve as a prokaryotic 'adaptive' immune system, protecting
      against foreign DNA elements such as bacteriophages. CRISPR-Cas systems function
      by incorporating short DNA 'spacers', homologous to invading DNA sequences, into
      a CRISPR array (adaptation). The array is then transcribed and matured into RNA
      molecules (maturation) that target homologous DNA for cleavage (interference). It
      is unclear how these three stages could occur quickly enough in a naive phage
      infected cell to interfere with phage replication before this cell would be
      irrevocably damaged by the infection. Here we demonstrate that cells can acquire
      spacers from defective phages at a rate directly proportional to the quantity of
      replication-deficient phages to which the cells are exposed. This process is
      reminiscent of immunization in humans by vaccination with inactivated viruses. 

PMID- 25056269
TI  - Synthesis and immunological evaluation of self-adjuvanting MUC1-macrophage
      activating lipopeptide 2 conjugate vaccine candidates.
AB  - We describe herein the synthesis and immunological evaluation of self-adjuvanting
      mucin 1 (MUC1)-macrophage activating lipopeptide 2 (MALP2) (glyco)peptide vaccine
      candidates. Vaccine constructs were shown to induce high titres of class-switched
      IgG antibodies in C57BL/6 mice after four immunisations despite the lack of a
      helper T cell epitope. 

PMID- 25056271
TI  - HNCA+, HNCO+, and HNCACB+ experiments: improved performance by simultaneous
      detection of orthogonal coherence transfer pathways.
AB  - Three experiments, BEST-TROSY HNCA+, HNCO+ and HNCACB+ are presented for
      sequential backbone resonance assignment of (13)C, (15)N labelled proteins. The
      novelty of these experiments with respect to conventional pulse sequences is the
      detection of additional orthogonal coherence transfer pathways that results in
      enhanced sensitivity for sequential correlations without significantly
      compromising the intensity of intra-residue correlation peaks. In addition, a 2
      step phase cycle separates peaks originating from the orthogonal coherence
      transfer pathways in 2 sub-spectra, thus providing similar information as
      obtained from performing a pair of sequential and intra-residue correlation
      experiments. 

PMID- 25056272
TI  - Protein structure prediction: assembly of secondary structure elements by basin
      hopping.
AB  - The prediction of protein tertiary structure from primary structure remains a
      challenging task. One possible approach to this problem is the application of
      basin-hopping global optimization combined with an all-atom force field. In this
      work, the efficiency of basin-hopping is improved by introducing an approach that
      derives tertiary structures from the secondary structure assignments of
      individual residues. This approach is termed secondary-to-tertiary basin-hopping
      and benchmarked for three miniproteins: trpzip, trp-cage and ER-10. For each of
      the three miniproteins, the secondary-to-tertiary basin-hopping approach
      successfully and reliably predicts their three-dimensional structure. When it is
      applied to larger proteins, correctly folded structures are obtained. It can be
      concluded that the assembly of secondary structure elements using basin-hopping
      is a promising tool for de novo protein structure prediction. 

PMID- 25056270
TI  - A survey of factors influencing career preference in new-entrant and exiting
      medical students from four UK medical schools.
AB  - BACKGROUND: Workforce planning is a central issue for service provision and has
      consequences for medical education. Much work has been examined the career
      intentions, career preferences and career destinations of UK medical graduates
      but there is little published about medical students career intentions. How soon
      do medical students formulate careers intentions? How much do these intentions
      and preferences change during medical school? If they do change, what are the
      determining factors? Our aim was to compare medical students' career preferences
      upon entry into and exit from undergraduate medical degree programmes. METHODS:
      This was a cross-sectional questionnaire survey. Two cohorts [2009-10, 2010-11]
      of first and final year medical students at the four Scottish graduating medical
      schools took part in career preference questionnaire surveys. Questions were
      asked about demographic factors, career preferences and influencing factors.
      RESULTS: The response rate was 80.9% [2682/3285]. Significant differences were
      found across the four schools, most obviously in terms of student origin
      [Scotland, rest of UK or overseas], age group, and specialty preferences in Year
      1 and Year 5. Year 1 and Year 5 students' specialty preferences also differed
      within each school and, while there were some common patterns, each medical
      school had a different profile of students' career preferences on exit. When the
      analysis was adjusted for demographic and job-related preferences, specialty
      preferences differed by gender, and wish for work-life balance and intellectual
      satisfaction. CONCLUSIONS: This is the first multi-centre study exploring
      students' career preferences and preference influences upon entry into and exit
      from undergraduate medical degree programmes. We found various factors influenced
      career preference, confirming prior findings. What this study adds is that, while
      acknowledging student intake differs by medical school, medical school itself
      seems to influence career preference. Comparisons across medical school
      populations must therefore control for differences in input [the students] as
      well as context and process [the medical school] when looking at output [e.g.,
      performance]. A robust, longitudinal study is required to explore how medical
      students' career preferences change as they progress through medical school and
      training to understand the influence of the learning environment on training
      choice and outcomes.

PMID- 25056273
TI  - The K898E germline variant in the PP1-binding motif of BRCA1 causes defects in
      DNA Repair.
AB  - BRCA1 is a phosphoprotein involved in many biological processes, including
      transcription, ubiquitination, checkpoint control, homologous recombination, and
      DNA repair. We have demonstrated that protein phosphatase 1alpha (PP1alpha)
      interacts with BRCA1 via a PP1-binding motif (898)KVTF(901), and can
      dephosphorylate multiple serine residues phosphorylated by checkpoint kinases. A
      K898E germline missense variant in the PP1-binding motif of BRCA1 has been found
      in an Ashkenazi patient and a non-Ashkenazi Argentinean patient with breast and
      ovarian cancer, but its clinical significance is still unknown. Here we report
      that the lysine residue in the PP1-binding motif of BRCA1 is highly conserved
      across many mammalian species. The K898E mutation interferes with the interaction
      between BRCA1 and PP1alpha. Moreover, while the expression of wild-type BRCA1 in
      Brca1-deficient cells improved cell survival after DNA damage induced by ionizing
      radiation (IR), expression of BRCA1 K898E proved unable to enhance cell survival.
      DNA damage repair mechanisms remained defective in these BRCA1 K898E
      reconstituted cells, as revealed by the comet assay and IR-induced Rad51 foci
      formation assay. These results reflect the significance of the interaction
      between BRCA1 and PP1, and indicate that the K898E variant may render carriers
      susceptible to DNA damage and malignant transformation. 

PMID- 25056274
TI  - Neonatal jaundice and increased risk of attention-deficit hyperactivity disorder:
      a population-based cohort study.
AB  - BACKGROUND: Previous studies have posited conflicting results regarding the
      relationship between neonatal jaundice and the subsequent risk of attention
      deficit hyperactivity disorder (ADHD). We therefore performed a large population
      study with a defined neonatal jaundice cohort to investigate the incidence and
      risk of physician-diagnosed ADHD in Taiwan. METHODS: From 2000 to 2004, 24,950
      neonatal jaundice cases and 69,964 matched nonjaundice controls were identified.
      At the end of 2008, the incidence rate and hazard ratios (HRs) of physician
      diagnosed ADHD were calculated. RESULTS: The incidence of ADHD was 2.48-fold
      greater in the jaundice cohort than in the nonjaundice cohort (3.84 vs. 1.51 per
      100,000 person-years) in the study period. The HR of ADHD was substantially
      greater for male, preterm, and low-birth-weight infants with neonatal jaundice.
      The risk of developing ADHD in the jaundice cohort was greater after a diagnosis
      of neonatal jaundice for more than 6 years (HR: 2.64; 95% confidence interval:
      2.13-3.28). The risk of ADHD increased for neonates with higher serum bilirubin
      levels requiring phototherapy and with longer admission days. CONCLUSION:
      Neonates with jaundice are at high risk for developing physician-diagnosed ADHD
      during their growth period. A risk alert regarding neurologic consequences is
      urgently required after a neonatal jaundice diagnosis. Additional studies should
      be conducted to clarify the pathogenesis of these relationships.

PMID- 25056275
TI  - Sphingosine-1-phosphate and its effect on glucose deprivation/glucose reload
      stress: from gene expression to neuronal survival.
AB  - Sphingosine kinase-1 (Sphk1-1, EC 2.7.1.91) is a regulator of pro-survival
      signalling, and its alterations have been observed in Alzheimer's disease, brain
      ischemia and other neurological disorders. In this study we addressed the
      question whether Sphk1 and its product, sphingosine-1-phosphate (S1P), play a
      significant role in glucose deprivation (GD)/glucose reload (GR) stress in
      hippocampal neuronal cells (HT22). It was found that GD (6 h) followed by 24 h of
      GR evoked enhancement of the free radical level and neuronal HT22 cell death.
      Moreover, the significantly stronger gene expression for the pro-apoptotic Bax
      protein and down-regulation of the anti-apoptotic Bcl-2 and Bcl-XL proteins were
      observed. Concomitantly, this stress up-regulated: gene expression, protein level
      and activity of Sphk1. Exogenous S1P at 1 MUM concentration and the other
      agonists of the S1P1 receptor (SEW 2871 and P-FTY720) enhanced HT22 cell
      viability affected by GD/GR stress. This mechanism is mediated by S1P receptor(s)
      signalling and by the activation of gene expression for Bcl-2 and Bcl-XL.
      Summarising, our data suggest that sphingolipid metabolism may play an important
      role in the early events that take place in neuronal cell survival/death under
      GD/GR stress. Our data demonstrate that exogenous S1P, through the activation of
      specific receptors S1P1 and S1P3 signalling pathways, regulates the gene
      expression for anti-apoptotic proteins and enhances neuronal cell survival
      affected by GD/GR stress. 

PMID- 25056276
TI  - Angle-resolved photoemission spectroscopy study on graphene using circularly
      polarized light.
AB  - We have investigated graphene using circularly polarized light via angle-resolved
      photoemission spectroscopy. We observe that photoelectron intensity rotates
      around a constant energy contour towards the opposite direction upon changing the
      chirality of light. Interestingly, the circular dichroism is found to be
      asymmetric with respect to the Dirac energy, which is not explained by the Berry
      phase effect (Liu et al 2011 Phys. Rev. Lett. 107 166803). We also report that
      the energy spectra taken using the light with different chiralities show a finite
      separation from each other. We discuss possible origins of the unusual circular
      dichroism observed in graphene. 

PMID- 25056277
TI  - The median effective seated time for hypotension induced by spinal anesthesia at
      Cesarean delivery with two doses of hyperbaric bupivacaine: a randomized up-down
      sequential allocation study.
AB  - BACKGROUND: Extending the time a parturient is left sitting after induction of
      spinal anesthesia (i.e., the seated time) has had varying success in decreasing
      hypotension at Cesarean delivery. This may be due to the current lack of
      information concerning the dose-response relationship of seated time and rates of
      hypotension. METHODS: Term parturients scheduled for Cesarean delivery were
      randomized to receive 11.25 or 15.0 mg of 0.75% intrathecal hyperbaric
      bupivacaine, and they remained seated after injection for a length of time
      determined by an up-down sequential method. They were then placed in a wedged
      position and their blood pressure was measured every minute. Pre-delivery
      hypotension was considered present if there was a > 20% from baseline drop in
      systolic blood pressure. The seated time at which 50% of parturients avoided pre
      delivery hypotension (median effective seated time) was determined with isotonic
      regression. RESULTS: Fifty patients were studied. For the 11.25-mg and 15.0-mg
      groups, the median effective seated time (95% confidence interval [CI]) was 130
      sec (95% CI 117 to 150) and 385 sec (95% CI 381 to 396), respectively.
      CONCLUSIONS: There exists a seated time after intrathecal injection of hyperbaric
      bupivacaine where 50% of parturients do not experience hypotension. This seated
      time increases with an increased dose of bupivacaine. Further work is required to
      determine the full relationship between seated time and hypotension for other
      doses of anesthetic and to investigate the clinical utility of this technique for
      prevention of hypotension. This trial was registered at www.clinicaltrials.gov
      (NCT01561274).

PMID- 25056279
TI  - 63rd Annual Scientific Sessions of the American College of Cardiology: 29-31
      March 2014; Washington, DC, USA.

PMID- 25056280
TI  - Photochemical transformations accelerated in continuous-flow reactors: basic
      concepts and applications.
AB  - Continuous-flow photochemistry is used increasingly by researchers in academia
      and industry to facilitate photochemical processes and their subsequent scale-up.
      However, without detailed knowledge concerning the engineering aspects of
      photochemistry, it can be quite challenging to develop a suitable photochemical
      microreactor for a given reaction. In this review, we provide an up-to-date
      overview of both technological and chemical aspects associated with photochemical
      processes in microreactors. Important design considerations, such as light
      sources, material selection, and solvent constraints are discussed. In addition,
      a detailed description of photon and mass-transfer phenomena in microreactors is
      made and fundamental principles are deduced for making a judicious choice for a
      suitable photomicroreactor. The advantages of microreactor technology for
      photochemistry are described for UV and visible-light driven photochemical
      processes and are compared with their batch counterparts. In addition, different
      scale-up strategies and limitations of continuous-flow microreactors are
      discussed. 

PMID- 25056281
TI  - Malignant adenomyoepithelioma combined with adenoid cystic carcinoma of the
      breast: a case report and literature review.
AB  - BACKGROUND: Malignant adenomyoepithelioma and adenoid cystic carcinoma are both
      rare malignant epithelial-myoepithelial tumors of the breast. We report a very
      rare case with a malignant adenomyoepithelioma combining with adenoid cystic
      carcinoma in a single mass. CASE PRESENTATION: A 61-year-old female presented
      with a palpable painless mass in the right breast. Mammography revealed a large
      irregular dense shadow without obvious internal calcification. A simple
      lumpectomy was performed, and a 1.6cm well-circumscribed pale-tan nodule was
      presented. Histologically, the nodule was composed of two obscure lobules. One
      exhibited typical histological image of adenoid cystic carcinoma, the other one
      showed the image of epithelial-myoepithelial carcinoma of salivary gland, and
      support the diagnosis of biphasic malignant adenomyoepithelioma. Transition
      between the two lobules was gradual. Immunohistochemically, CK18 and P63
      highlighted the epithelial and myoepithelial cells respectively in both lesions.
      CD117 was positive in the epithelial cells of adenoid cystic carcinoma, but was
      totally negative in malignant adenomyoepithelioma. CONCLUSION: This report is, to
      our knowledge, the first case that combines these two tumors in a single mass. In
      addition, we present a review of the literature. The histogenesis of these tumors
      is also discussed. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://med.motic.com/MoticGallery/Slide?id=D562817E-23C2-4F72-9823
      86EF6DA40005&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025 and
      http://med.motic.com/MoticGallery/Slide?id=38BB7126-6FFB-4B66-A208
      B8C0F528DCA8&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025.

PMID- 25056282
TI  - Chemoselective carbophilic addition of alpha-diazoesters through ligand
      controlled gold catalysis.
AB  - The chemoselective addition of arenes and 1,3-diketones to alpha-aryldiazoesters
      was achieved through ligand-controlled gold catalysis. Unlike a dirhodium
      catalyst (which promotes C(sp3)-H insertion and cyclopropanation) and a copper
      catalyst (which catalyzes O-H and N-H insertions), the gold catalyst with an
      electron-deficient phosphite as the ancillary ligand exclusively gave the
      carbophilic addition product, thus representing a new and efficient approach to
      form "carbophilic carbocations", which selectively react with carbon
      nucleophiles.

PMID- 25056283
TI  - Thermodriven micrometer-scale aqueous-phase separation of amphiphilic
      oligoethylene glycol analogues.
AB  - Thermoresponsive materials with a lower critical solution temperature (LCST) are
      receiving growing attention, of which examples of non-polymeric small molecules
      are limited. Monodisperse oligoethylene glycol amphiphiles that contain aromatic
      units with a LCST in water have been developed and applied to peptide extraction.
      Concentration-dependent hysteretic transmittance changes were observed in
      response to temperature elevation and reduction. Dynamic light scattering
      measurements and phase contrast microscopy revealed the formation of micrometer
      sized aggregates upon heating at a concentration above 5.0 mM; these aggregates
      self-assembled to form larger aggregates upon cooling before dissolution. The
      "interaggregate" interactions are likely to cause the hysteretic behavior. As an
      application of this thermodriven phase separation, selective extraction of
      peptide fragments containing high percentages of hydrophobic and aromatic amino
      acid residues was successfully demonstrated. 

PMID- 25056284
TI  - Development of clinical models for predicting erectile function after localized
      prostate cancer treatment.
AB  - OBJECTIVES: To develop clinical prediction models estimating the probability of
      maintaining erections adequate for intercourse 2 years after prostate cancer
      treatment, based on pretreatment characteristics. METHODS: Study participants
      consisted of prostate cancer patients with localized disease and functional
      erections before undergoing surgery (n = 536) or radiation therapy (n = 240) at a
      single USA institution. Baseline patient- and treatment-related data were
      collected from a clinical database and through chart review. Erectile function at
      2 years post-treatment was prospectively assessed through a self-administered
      single-item measure. Multivariate logistic regression using backward selection
      was used to derive clinical prediction models to predict erectile function at 2
      years for surgery and radiation therapy patients; the models were internally
      validated using bootstrapping methods. RESULTS: The final prediction model for
      surgery patients included the predictor variables of age, body mass index,
      smoking, diabetes, hypertension and nerve-sparing procedures, whereas the model
      for radiation therapy patients included hypertension, risk category and radiation
      technique. The new models showed acceptable calibration and discrimination: c
      statistic = 0.71 (95% confidence interval 0.68-0.76) for surgery and 0.66 (95%
      confidence interval 0.61-0.74) for radiation therapy models. CONCLUSIONS: New
      clinical prediction models based on patient and treatment characteristics show
      promising accuracy in predicting erectile function at 2 years in patients treated
      with surgery and radiation for localized prostate cancer. More work is required
      to confirm and validate these models in different patient populations.

PMID- 25056286
TI  - Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in
      polarized epithelial cysts.
AB  - GLUT2 is a facilitative glucose transporter, expressed in polarized epithelial
      cells of the liver, intestine, kidney and pancreas, where it plays a critical
      role in glucose homeostasis. Together with SGLT1/2, it mediates glucose
      absorption in metabolic epithelial tissues, where it can be translocated apically
      upon high glucose exposure. To track the subcellular localization and dynamics of
      GLUT2, we created an mCherry-hGLUT2 fusion protein and expressed it in
      multicellular kidney cysts, a major site of glucose reabsorption. Live imaging of
      GLUT2 enabled us to avoid the artefactual localization of GLUT2 in fixed cells
      and to confirm the apical GLUT2 model. Live cell imaging showed a rapid 15 +/- 3
      min PKC-dependent basal-to-apical translocation of GLUT2 in response to glucose
      stimulation and a fourfold slower basolateral translocation under starvation.
      These results mark the physiological importance of responding quickly to rising
      glucose levels. Importantly, we show that phloretin, an apple polyphenol,
      inhibits GLUT2 translocation in both directions, suggesting that it exerts its
      effect by PKC inhibition. Subcellular localization studies demonstrated that
      GLUT2 is endocytosed through a caveolae-dependent mechanism, and that it is at
      least partly recovered in Rab11A-positive recycling endosome. Our work
      illuminates GLUT2 dynamics, providing a platform for drug development for
      diabetes and hyperglycaemia. 

PMID- 25056287
TI  - Revision of the classical dopamine D2 agonist pharmacophore based on an
      integrated medicinal chemistry, homology modelling and computational docking
      approach.
AB  - The scientific advances during the 1970ies and 1980ies within the field of
      dopaminergic neurotransmission enabled the development of a pharmacophore that
      became the template for design and synthesis of dopamine D2 agonists during the
      following four decades. A major drawback, however, is that this model fails to
      accommodate certain classes of restrained dopamine D2 agonists including ergoline
      structures. To accommodate these, a revision of the original model was required.
      The present study has addressed this by an extension of the original model
      without compromising its obvious qualities. The revised pharmacophore contains an
      additional hydrogen bond donor feature, which is required for it to accommodate
      ergoline structures in a low energy conformation and in accordance with the
      steric restrictions dictated by the original model. The additional pharmacophore
      feature suggests ambiguity in the binding mode for certain compounds, including a
      series of ergoline analogues, which was reported recently. The ambiguity was
      confirmed by docking to a homology model of the D2 receptor as well as by
      pharmacological characterization of individual enantiomers of one of the
      analogues. The present research also addresses the potential of designing ligands
      that interact with the receptor in a large, distal cavity of the dopamine D2
      receptor that has not previously been studied systematically. The pharmacological
      data indicate that this area may be a major determinant for both the dopamine D2
      affinity and efficacy, which remains to be explored in future studies.

PMID- 25056289
TI  - Effects of antimicrobial peptide L-K6, a temporin-1CEb analog on oral pathogen
      growth, Streptococcus mutans biofilm formation, and anti-inflammatory activity.
AB  - Dental caries and periodontitis are common bacterial mouth infections. As a
      potentially attractive substitute for conventional antibiotics, antimicrobial
      peptides have been widely tested and used for controlling bacterial infections.
      In this study, we tested the efficacy of the peptides from the skin secretions of
      Rana chensinensis for killing several major cariogenic and periodontic pathogens
      as well as Candida albicans. L-K6, a temporin-1CEb analog, exhibited high
      antimicrobial activity against the tested oral pathogens and was able to inhibit
      Streptococcus mutans biofilm formation and reduce 1-day-old S. mutans biofilms
      with a minimum biofilm inhibitory concentration and reducing concentration of
      3.13 and 6.25 MUM, respectively. The results of confocal laser scanning
      microscopy demonstrated that the peptide significantly reduced cell viability
      within oral biofilms. Furthermore, as little as 5 MUM L-K6 significantly
      inhibited lipopolysaccharide (LPS)- and interleukin-1beta-induced productions of
      interleukin-8 and tumor necrosis factor-alpha from THP-1 monocytic cells. This
      anti-inflammatory activity is associated with the binding of L-K6 to LPS and
      neutralizing LPS-induced proinflammatory responses in THP-1 cells, as well as
      dissociating LPS aggregates. Our results suggest that L-K6 may have potential
      clinical applications in treating dental caries by killing S. mutans within
      dental plaque and acting as anti-inflammatory agents in infected tissues.

PMID- 25056288
TI  - Genome sequence and virulence variation-related transcriptome profiles of
      Curvularia lunata, an important maize pathogenic fungus.
AB  - BACKGROUND: Curvularia lunata is an important maize foliar fungal pathogen that
      distributes widely in maize growing area in China. Genome sequencing of the
      pathogen will provide important information for globally understanding its
      virulence mechanism. RESULTS: We report the genome sequences of a highly virulent
      C. lunata strain. Phylogenomic analysis indicates that C. lunata was evolved from
      Bipolaris maydis (Cochliobolus heterostrophus). The highly virulent strain has a
      high potential to evolve into other pathogenic stains based on analyses on
      transposases and repeat-induced point mutations. C. lunata has a smaller
      proportion of secreted proteins as well as B. maydis than entomopathogenic fungi.
      C. lunata and B. maydis have a similar proportion of protein-encoding genes
      highly homologous to experimentally proven pathogenic genes from pathogen-host
      interaction database. However, relative to B. maydis, C. lunata possesses not
      only many expanded protein families including MFS transporters, G-protein coupled
      receptors, protein kinases and proteases for transport, signal transduction or
      degradation, but also many contracted families including cytochrome P450,
      lipases, glycoside hydrolases and polyketide synthases for detoxification,
      hydrolysis or secondary metabolites biosynthesis, which are expected to be
      crucial for the fungal survival in varied stress environments. Comparative
      transcriptome analysis between a lowly virulent C. lunata strain and its
      virulence-increased variant induced by resistant host selection reveals that the
      virulence increase of the pathogen is related to pathways of toxin and melanin
      biosynthesis in stress environments, and that the two pathways probably have some
      overlaps. CONCLUSIONS: The data will facilitate a full revelation of pathogenic
      mechanism and a better understanding of virulence differentiation of C. lunata.

PMID- 25056290
TI  - Modeling the effects of biomass accumulation on the performance of a biotrickling
      filter packed with PUF support for the alkaline biotreatment of dimethyl
      disulfide vapors in air.
AB  - Excess biomass buildup in biotrickling filters leads to low performance. The
      effect of biomass accumulation in a biotrickling filter (BTF) packed with
      polyurethane foam (PUF) was assessed in terms of hydrodynamics and void space
      availability in a system treating dimethyl disulfide (DMDS) vapors with an
      alkaliphilic consortium. A sample of colonized support from a BTF having been
      operating for over a year was analyzed, and it was found that the BTF void bed
      fraction was reduced to almost half of that calculated initially without biomass.
      Liquid flow through the examined BTF yielded dispersion coefficient values of
      0.30 and 0.72 m(2) h(-1), for clean or colonized PUF, respectively. 3D images of
      attached biomass obtained with magnetic resonance imaging allowed to calculate
      the superficial area and the biofilm volume percentage and depth as 650 m(2) m(
      3), 35%, and 0.6 mm respectively. A simplified geometric approximation of the
      complex PUF structure was proposed using an orthogonal 3D mesh that predicted 600
      m(2) m(-3) for the same biomass content. With this simplified model, it is
      suggested that the optimum biomass content would be around 20% of bed volume. The
      activity of the microorganisms was evaluated by respirometry and the kinetics
      represented with a Haldane equation type. Experimentally determined parameters
      were used in a mathematical model to simulate the DMDS elimination capacity (EC),
      and better description was found when the removal experimental data were matched
      with a model including liquid axial dispersion in contrast to an ideal plug flow
      model.

PMID- 25056291
TI  - Successful expression of a novel bacterial gene for pinoresinol reductase and its
      effect on lignan biosynthesis in transgenic Arabidopsis thaliana.
AB  - Pinoresinol reductase and pinoresinol/lariciresinol reductase play important
      roles in an early step of lignan biosynthesis in plants. The activities of both
      enzymes have also been detected in bacteria. In this study, pinZ, which was first
      isolated as a gene for bacterial pinoresinol reductase, was constitutively
      expressed in Arabidopsis thaliana under the control of the cauliflower mosaic
      virus 35S promoter. Higher reductive activity toward pinoresinol was detected in
      the resultant transgenic plants but not in wild-type plant. Principal component
      analysis of data from untargeted metabolome analyses of stem, root, and leaf
      extracts of the wild-type and two independent transgenic lines indicate that pinZ
      expression caused dynamic metabolic changes in stems, but not in roots and
      leaves. The metabolome data also suggest that expression of pinZ influenced the
      metabolisms of lignan and glucosinolates but not so much of neolignans such as
      guaiacylglycerol-8-O-4'-feruloyl ethers. In-depth quantitative analysis by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) indicated that amounts of
      pinoresinol and its glucoside form were markedly reduced in the transgenic plant,
      whereas the amounts of glucoside form of secoisolariciresinol in transgenic
      roots, leaves, and stems increased. The detected levels of lariciresinol in the
      transgenic plant following beta-glucosidase treatment also tended to be higher
      than those in the wild-type plant. Our findings indicate that overexpression of
      pinZ induces change in lignan compositions and has a major effect not only on
      lignan biosynthesis but also on biosynthesis of other primary and secondary
      metabolites. 

PMID- 25056292
TI  - Simultaneous enrichment of denitrifying methanotrophs and anammox bacteria.
AB  - Interaction between denitrifying anaerobic methane oxidation (DAMO) and anaerobic
      ammonium oxidation (anammox) processes may play an important role in global
      carbon and nitrogen cycles. In this study, a coculture of denitrifying
      methanotrophs (DAMO archaea and DAMO bacteria) and anammox bacteria, initially
      sourced from the environment, was enriched with a supply of methane, nitrate, and
      ammonium. After a 4.5-month enrichment, simultaneous oxidation of methane and
      ammonium and reduction of nitrate were observed. The highest rate of nitrate
      reduction in the suspended DAMO culture was 4.84 mmol/L/day, and simultaneously,
      the highest ammonium removal rate was 4.07 mmol/L/day. Fluorescence in situ
      hybridization and analysis of 16S rRNA gene clone libraries revealed the
      coexistence of DAMO archaea, DAMO bacteria, and anammox bacteria. The development
      of anammox bacteria might reduce the enrichment time of DAMO microorganisms and
      promote the activity of DAMO archaea. The activity of the reactor fluctuated
      during the long-term operation, which might be caused by the formation of
      microbial clusters whereby DAMO archaea grew in aggregates that were surrounded
      by anammox and DAMO bacteria. This study is the first to demonstrate that it is
      feasible to establish a coculture of DAMO archaea, DAMO bacteria, and anammox
      bacteria from environmental inocula.

PMID- 25056294
TI  - A novel international initiative to promote academic oncology amongst medical
      students.

PMID- 25056293
TI  - A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation
      defect in Wolfram syndrome type 2.
AB  - BACKGROUND: Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and
      genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes
      mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical
      phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and
      psychiatric disorders, and for the presence of bleeding upper intestinal ulcers
      and defective platelet aggregation. After the first report of consanguineous
      Jordanian patients, no further cases of WFS2 have been reported worldwide. We
      describe the first Caucasian patient affected by WFS2. CASE PRESENTATION: The
      proband was a 17 year-old girl. She presented diabetes mellitus, optic
      neuropathy, intestinal ulcers, sensorineural hearing loss, and defective platelet
      aggregation to ADP. Genetic testing showed a novel homozygous intragenic deletion
      of CISD2 in the proband. Her brother and parents carried the heterozygous
      mutation and were apparently healthy, although they showed subclinical defective
      platelet aggregation. Long runs of homozygosity analysis from SNP-array data did
      not show any degree of parental relationship, but the microsatellite analysis
      confirmed the hypothesis of a common ancestor. CONCLUSION: Our patient does not
      show optic atrophy, one of the main diagnostic criteria for WFS, but optic
      neuropathy. Since the "asymptomatic" optic atrophy described in Jordanian
      patients is not completely supported, we could suppose that the ocular pathology
      in Jordanian patients was probably optic neuropathy and not optic atrophy.
      Therefore, as optic atrophy is required as main diagnostic criteria of WFS, it
      might be that the so-called WFS2 could not be a subtype of WFS. In addition, we
      found an impaired aggregation to ADP and not to collagen as previously reported,
      thus it is possible that different experimental conditions or inter-patient
      variability can explain different results in platelet aggregation. Further
      clinical reports are necessary to better define the clinical spectrum of this
      syndrome and to re-evaluate its classification.

PMID- 25056295
TI  - Characterisation of an aerosol exposure system to evaluate the genotoxicity of
      whole mainstream cigarette smoke using the in vitro gammaH2AX assay by high
      content screening.
AB  - BACKGROUND: The genotoxic effect of cigarette smoke is routinely measured by
      treating cells with cigarette Particulate Matter (PM) at different dose levels in
      submerged cell cultures. However, PM exposure cannot be considered as a complete
      exposure as it does not contain the gas phase component of the cigarette smoke.
      The in vitro gammaH2AX assay by High Content Screening (HCS) has been suggested
      as a complementary tool to the standard battery of genotoxicity assays as it
      detects DNA double strand breaks in a high-throughput fashion. The aim of this
      study was to further optimise the in vitro gammaH2AX assay by HCS to enable
      aerosol exposure of human bronchial epithelial BEAS-2B cells at the air-liquid
      interface (ALI). METHODS: Whole mainstream cigarette smoke (WMCS) from two
      reference cigarettes (3R4F and M4A) were assessed for their genotoxic potential.
      During the study, a further characterisation of the Borgwaldt RM20S(r) aerosol
      exposure system to include single dilution assessment with a reference gas was
      also carried out. RESULTS: The results of the optimisation showed that both
      reference cigarettes produced a positive genotoxic response at all dilutions
      tested. However, the correlation between dose and response was low for both 3R4F
      and M4A (Pearson coefficient, r = -0.53 and -0.44 respectively). During the
      additional characterisation of the exposure system, it was observed that several
      pre-programmed dilutions did not perform as expected. CONCLUSIONS: Overall, the
      in vitro gammaH2AX assay by HCS could be used to evaluate WMCS in cell cultures
      at the ALI. Additionally, the extended characterisation of the exposure system
      indicates that assessing the performance of the dilutions could improve the
      existing routine QC checks.

PMID- 25056296
TI  - Peptoniphilus stercorisuis sp. nov., isolated from a swine manure storage tank
      and description of Peptoniphilaceae fam. nov.
AB  - A species of a previously unknown Gram-positive-staining, anaerobic, coccus
      shaped bacterium recovered from a swine manure storage tank was characterized
      using phenotypic, chemotaxonomic, and molecular taxonomic methods. Comparative
      16S rRNA gene sequencing studies and biochemical characteristics demonstrated
      that this organism is genotypically and phenotypically distinct, and represents a
      previously unknown sub-line within the order Clostridiales, within the phylum
      Firmicutes. Pairwise sequence analysis demonstrated that the novel organism
      clustered within the genus Peptoniphilus, most closely related to Peptoniphilus
      methioninivorax sharing a 16S rRNA gene sequence similarity of 95.5%. The major
      long-chain fatty acids were found to be C14:0 (22.4%), C16:0 (15.6%),
      C16:1omega7c (11.3%) and C16 : 0 ALDE (10.1%) and the DNA G +C content was 31.8
      mol%. Based upon the phenotypic and phylogenetic findings presented, a novel
      species Peptoniphilus stercorisuis sp. nov. is proposed. The type strain is SF
      S1(T) ( = DSM 27563(T) = NBRC 109839(T)). In addition, it is proposed to
      accommodate the genera Peptoniphilus, Anaerococcus, Anaerosphaera, Finegoldia,
      Gallicola, Helcococcus, Murdochiella and Parvimonas in a new family of the order
      Clostridiales, for which the name Peptoniphilaceae fam. nov. is proposed; the
      type genus of the family is Peptoniphilus.

PMID- 25056297
TI  - Shewanella dovemarinesis sp. nov., a psychrotolerant bacterium isolated from Mid
      Atlantic Ridge deep-sea sediments.
AB  - Strains MAR441T and MAR445 were isolated from Mid-Atlantic Ridge (MAR) sediments
      with a depth of 2,734 m, and found to be member of the genus Shewanella. The
      strains were rod shaped, pigmented, non-motile, and capable of anaerobic growth
      either by fermentation of carbohydrates or by anaerobic respiration. The strains
      utilized a variety of electron acceptors, including nitrate and ferric compounds
      and could utilize peptone when grown anaerobically in a two-chambered microbial
      fuel cell (MFC), which use carbon cloth electrodes and deliver a stable power
      output of ~150-200 mW/m2. The major fatty acids were typical of the genus
      Shewanella, with major components of C13:0, iso-C13:0, iso-C15:0, C16:0,
      C16:1omega7c, C18:1omega7c and C20:5omega3 fatty acids. The DNA G+C content of
      strains MAR441T and MAR445 were 42.4 mol %. 16S rRNA gene sequence analysis
      indicated that strains MAR441T and MAR445 were most closely related to Shewanella
      olleyana (sequence similarities 97.9 %). DNA-DNA hybridization demonstrated only
      15.6-37.2 % relatedness between strain MAR441T and the type strains of related
      Shewanella species. Phenotypic characteristics confirmed that these isolates
      constituted a novel species of the genus Shewanella. The type strain of
      Shewanella dovemarinensis is MAR441T (=ATCC BAA-2408 T =DSM24955 T).

PMID- 25056298
TI  - Microbacterium mangrovi sp. nov., an amylolytic actinobacterium isolated from
      mangrove forest soil.
AB  - Strain MUSC 115(T) was isolated from mangrove soil of the Tanjung Lumpur river in
      the state of Pahang, Peninsular Malaysia. Cells of this strain stained Gram
      positive and were non-spore-forming, short rods that formed yellowish-white
      colonies on different agar media. The taxonomy of strain MUSC 115(T) was studied
      by a polyphasic approach, and the organism showed a range of phylogenetic and
      chemotaxonomic properties consistent with those of the genus Microbacterium. The
      cell-wall peptidoglycan was of type B2beta, containing the amino acids ornithine,
      alanine, glycine, glutamic acid and homoserine. The muramic acid was of the N
      glycolyl form. The predominant menaquinones detected were MK-12, MK-13 and MK-11.
      The polar lipids consisted of phosphatidylglycerol, phosphoglycolipid,
      diphosphatidylglycerol, two unidentified lipids, three unidentified phospholipids
      and four unidentified glycolipids. The major fatty acids of the cell membrane
      were anteiso-C15:0 and anteiso-C17:0. The whole-cell sugars detected were ribose,
      glucose, mannose and galactose. Based on the 16S rRNA gene sequence, strain MUSC
      115(T) showed the highest sequence similarity to Microbacterium immunditiarum SK
      18(T) (98.1%), M. ulmi XIL02(T) (97.8%) and M. arborescens DSM 20754(T) (97.5%)
      and lower sequence similarity to strains of other species of the genus
      Microbacterium. DNA-DNA hybridization experiments revealed a low level of DNA-DNA
      relatedness (less than 24%) between strain MUSC 115(T) and the type strains of
      closely related species. Furthermore, BOX-PCR fingerprint comparison also
      indicated that strain MUSC 115(T) represented a unique DNA profile. The DNA G+C
      content determined was 70.9 +/- 0.7 mol%, which is lower than that of M.
      immunditiarum SK 18(T). Based on the combination of genotypic and phenotypic
      data, it is proposed that strain MUSC 115(T) represents a novel species of the
      genus Microbacterium, for which the name Microbacterium mangrovi sp. nov. is
      proposed. The type strain is MUSC 115(T) ( = MCCC 1K00251(T) = DSM 28240(T) =
      NBRC 110089(T)).

PMID- 25056299
TI  - She's got a ticket to ride.

PMID- 25056300
TI  - Collagenous enterocolitis and maturity onset type 1 diabetes manifesting as
      uraemia, malabsorption and extreme weight loss.
AB  - A 37-year-old patient with type 1 diabetes had been recently diagnosed with
      collagenous colitis (CC) after sigmoidoscopy. She rapidly progressed from a
      fortnight of watery diarrhoea, to a malabsorptive state with severe dehydration
      and acute kidney injury. This necessitated admission to an intensive care unit
      for emergency dialysis. She was subsequently diagnosed with collagenous
      enterocolitis affecting gastric, small bowel and colonic mucosa which required
      systemic steroid therapy. Physicians caring for patients with CC should be aware
      of the potential extreme manifestations of upper gastrointestinal collagenous
      deposition. 

PMID- 25056301
TI  - Immunohistochemical analysis of a ruptured basilar top aneurysm autopsied 22
      years after embolization with Guglielmi detachable coils.
AB  - The authors report on the histologic and immunohistochemical analyses of a
      cerebral aneurysm embolized with platinum coils and with the longest observation
      period. A 58-year-old woman presenting with subarachnoid hemorrhage due to
      ruptured basilar top aneurysm was treated with Guglielmi detachable coils (GDC)
      22 years ago. She was the 15th case since the GDC was introduced. After she died
      of unrelated causes, an autopsy and thorough histologic examination were
      performed. Gross examination revealed no adhesion between the aneurysm wall and
      the surrounding brain tissue. Histologic and immunohistochemical analyses
      demonstrated that the cavity of the aneurysm was filled with homogeneous
      collagenous fibrous tissue, while the neck was completely covered by a dense
      collagenous neointima and a smooth muscle cell layer. The unique histologic
      results of this case may contribute to a better understanding of the long-term
      evolution of the healing process in intracranial aneurysms successfully treated
      with the GDC. 

PMID- 25056302
TI  - Effective ultra-low doses of erlotinib in patients with EGFR sensitising
      mutation.
AB  - We describe three cases of patients with advanced adenocarcinoma of the lung and
      epidermal growth factor receptor (EGFR) mutation treated with erlotinib 25 mg/day
      and 25 mg every second day, being equal to one-sixth and one-twelfth of the
      recommended dose. The mean age of our patients was above 70 with a WHO
      performance status 1 before and during the treatment. The reasons for erlotinib
      dose reduction were rash, diarrhoea and fatigue. The decision was a result of
      lack of other treatment options and radiological response on standard doses. We
      did not observe any liver enzyme abnormalities. However, the post-treatment
      creatinine increased significantly. As of February 2014, our patients are still
      on treatment with tolerable side effects and improved quality of life. These
      findings indicate that some patients responding to erlotinib with noxious side
      effects could have clinical benefit in doses much lower than recommended. 

PMID- 25056303
TI  - Balloon angioplasty with secondary stenting for chronically occluded abdominal
      aorta in a high-risk patient.

PMID- 25056304
TI  - Acetic acid iontophoresis for the treatment of insertional Achilles tendonitis.

PMID- 25056305
TI  - The bias busters.

PMID- 25056306
TI  - Acute hypoxia affects P-TEFb through HDAC3 and HEXIM1-dependent mechanism to
      promote gene-specific transcriptional repression.
AB  - Hypoxia is associated with a variety of physiological and pathological conditions
      and elicits specific transcriptional responses. The elongation competence of RNA
      Polymerase II is regulated by the positive transcription elongation factor b (P
      TEFb)-dependent phosphorylation of Ser2 residues on its C-terminal domain. Here,
      we report that hypoxia inhibits transcription at the level of elongation. The
      mechanism involves enhanced formation of inactive complex of P-TEFb with its
      inhibitor HEXIM1 in an HDAC3-dependent manner. Microarray transcriptome profiling
      of hypoxia primary response genes identified ~79% of these genes being HEXIM1
      dependent. Hypoxic repression of P-TEFb was associated with reduced acetylation
      of its Cdk9 and Cyclin T1 subunits. Hypoxia caused nuclear translocation and co
      localization of the Cdk9 and HDAC3/N-CoR repressor complex. We demonstrated that
      the described mechanism is involved in hypoxic repression of the monocyte
      chemoattractant protein-1 (MCP-1) gene. Thus, HEXIM1 and HDAC-dependent
      deacetylation of Cdk9 and Cyclin T1 in response to hypoxia signalling alters the
      P-TEFb functional equilibrium, resulting in repression of transcription. 

PMID- 25056307
TI  - Engineering self-contained DNA circuit for proximity recognition and localized
      signal amplification of target biomolecules.
AB  - Biomolecular interactions have important cellular implications, however, a simple
      method for the sensing of such proximal events is lacking in the current
      molecular toolbox. We designed a dynamic DNA circuit capable of recognizing
      targets in close proximity to initiate a pre-programmed signal transduction
      process resulting in localized signal amplification. The entire circuit was
      engineered to be self-contained, i.e. it can self-assemble onto individual target
      molecules autonomously and form localized signal with minimal cross-talk. alpha
      thrombin was used as a model protein to evaluate the performance of the
      individual modules and the overall circuit for proximity interaction under
      physiologically relevant buffer condition. The circuit achieved good selectivity
      in presence of non-specific protein and interfering serum matrix and successfully
      detected for physiologically relevant alpha-thrombin concentration (50 nM-5 MUM)
      in a single mixing step without any further washing. The formation of localized
      signal at the interaction site can be enhanced kinetically through the control of
      temperature and probe concentration. This work provides a basic general framework
      from which other circuit modules can be adapted for the sensing of other
      biomolecular or cellular interaction of interest. 

PMID- 25056308
TI  - Translation inhibitors cause abnormalities in ribosome profiling experiments.
AB  - Ribosome profiling and high-throughput sequencing provide unprecedented
      opportunities for the analysis of mRNA translation. Using this novel method,
      several studies have demonstrated the widespread role of short upstream reading
      frames in translational control as well as slower elongation at the beginning of
      open reading frames in response to stress. Based on the initial studies, the
      importance of adding or omitting translation inhibitors, such as cycloheximide,
      was noted as it markedly affected ribosome coverage profiles. For that reason,
      many recent studies omitted translation inhibitors in the culture medium. Here,
      we investigate the influence of ranging cycloheximide concentrations on ribosome
      profiles in Saccharomyces cerevisiae and demonstrate that increasing the drug
      concentration can overcome some of the artifacts. We subjected cells to various
      manipulations and show that neither oxidative stress nor heat shock nor amino
      acid starvation affect translation elongation. Instead, the observations in the
      initial studies are the result of cycloheximide-inflicted artifacts. Likewise, we
      find little support for short upstream reading frames to be involved in
      widespread protein synthesis regulation under stress conditions. Our study
      highlights the need for better standardization of ribosome profiling methods. 

PMID- 25056309
TI  - New insights into the incorporation of natural suppressor tRNAs at stop codons in
      Saccharomyces cerevisiae.
AB  - Stop codon readthrough may be promoted by the nucleotide environment or drugs. In
      such cases, ribosomes incorporate a natural suppressor tRNA at the stop codon,
      leading to the continuation of translation in the same reading frame until the
      next stop codon and resulting in the expression of a protein with a new potential
      function. However, the identity of the natural suppressor tRNAs involved in stop
      codon readthrough remains unclear, precluding identification of the amino acids
      incorporated at the stop position. We established an in vivo reporter system for
      identifying the amino acids incorporated at the stop codon, by mass spectrometry
      in the yeast Saccharomyces cerevisiae. We found that glutamine, tyrosine and
      lysine were inserted at UAA and UAG codons, whereas tryptophan, cysteine and
      arginine were inserted at UGA codon. The 5' nucleotide context of the stop codon
      had no impact on the identity or proportion of amino acids incorporated by
      readthrough. We also found that two different glutamine tRNA(Gln) were used to
      insert glutamine at UAA and UAG codons. This work constitutes the first
      systematic analysis of the amino acids incorporated at stop codons, providing
      important new insights into the decoding rules used by the ribosome to read the
      genetic code. 

PMID- 25056310
TI  - Functional gene groups are concentrated within chromosomes, among chromosomes and
      in the nuclear space of the human genome.
AB  - Genomes undergo changes in organization as a result of gene duplications,
      chromosomal rearrangements and local mutations, among other mechanisms. In
      contrast to prokaryotes, in which genes of a common function are often organized
      in operons and reside contiguously along the genome, most eukaryotes show much
      weaker clustering of genes by function, except for few concrete functional
      groups. We set out to check systematically if there is a relation between gene
      function and gene organization in the human genome. We test this question for
      three types of functional groups: pairs of interacting proteins, complexes and
      pathways. We find a significant concentration of functional groups both in terms
      of their distance within the same chromosome and in terms of their dispersal over
      several chromosomes. Moreover, using Hi-C contact map of the tendency of
      chromosomal segments to appear close in the 3D space of the nucleus, we show that
      members of the same functional group that reside on distinct chromosomes tend to
      co-localize in space. The result holds for all three types of functional groups
      that we tested. Hence, the human genome shows substantial concentration of
      functional groups within chromosomes and across chromosomes in space. 

PMID- 25056311
TI  - Psip1/Ledgf p75 restrains Hox gene expression by recruiting both trithorax and
      polycomb group proteins.
AB  - Trithorax and polycomb group proteins are generally thought to antagonize one
      another. The trithorax family member MLL (myeloid/lymphoid or mixed-lineage
      leukemia) is presumed to activate Hox expression, counteracting polycomb-mediated
      repression. PC4 and SF2 interacting protein 1 (PSIP1)/p75, also known as LEDGF,
      whose PWWP domain binds to H3K36me3, interacts with MLL and tethers MLL fusion
      proteins to HOXA9 in leukaemias. Here we show, unexpectedly, that Psip1/p75
      regulates homeotic genes by recruiting not only MLL complexes, but also the
      polycomb group protein Bmi1. In Psip1(-/-) cells binding of Mll1/2, Bmi1 and the
      co-repressor Ctbp1 at Hox loci are all abrogated and Hoxa and Hoxd mRNA
      expression increased. Our data not only reveal a potential mechanism of action
      for Psip1 in the regulation of Hox genes but also suggest an unexpected interplay
      between proteins usually considered as transcriptional activators and repressors.

PMID- 25056312
TI  - Design and characterization of a dual-mode promoter with activation and
      repression capability for tuning gene expression in yeast.
AB  - Modularity in controlling gene expression artificially is becoming an essential
      aspect of synthetic biology. Artificial transcriptional control of gene
      expression is one of the most well-developed methods for the design of novel
      synthetic regulatory networks. Such networks are intended to help understand
      natural cellular phenomena and to enable new biotechnological applications.
      Promoter sequence manipulation with cis-regulatory elements is a key approach to
      control gene expression transcriptionally. Here, we have designed a promoter that
      can be both activated and repressed, as a contribution to the library of
      synthetic biological 'parts'. Starting with the minimal cytochrome C (minCYC)
      promoter in yeast, we incorporated five steroid hormone responsive elements
      (SHREs) and one lac operator site, respectively, upstream and downstream of the
      TATA box. This allows activation through the testosterone-responsive androgen
      receptor, and repression through the LacI repressor. Exposure to varying
      concentrations of testosterone (to vary activation) and IPTG (to vary repression)
      demonstrated the ability to tune the promoter's output curve over a wide range.
      By integrating activating and repressing signals, the promoter permits a useful
      form of signal integration, and we are optimistic that it will serve as a
      component in future regulatory networks, including feedback controllers. 

PMID- 25056313
TI  - The effect of tRNA levels on decoding times of mRNA codons.
AB  - The possible effect of transfer ribonucleic acid (tRNA) concentrations on codons
      decoding time is a fundamental biomedical research question; however, due to a
      large number of variables affecting this process and the non-direct relation
      between them, a conclusive answer to this question has eluded so far researchers
      in the field. In this study, we perform a novel analysis of the ribosome
      profiling data of four organisms which enables ranking the decoding times of
      different codons while filtering translational phenomena such as experimental
      biases, extreme ribosomal pauses and ribosome traffic jams. Based on this
      filtering, we show for the first time that there is a significant correlation
      between tRNA concentrations and the codons estimated decoding time both in
      prokaryotes and in eukaryotes in natural conditions (-0.38 to -0.66, all P values
      <0.006); in addition, we show that when considering tRNA concentrations, codons
      decoding times are not correlated with aminoacyl-tRNA levels. The reported
      results support the conjecture that translation efficiency is directly influenced
      by the tRNA levels in the cell. Thus, they should help to understand the
      evolution of synonymous aspects of coding sequences via the adaptation of their
      codons to the tRNA pool. 

PMID- 25056314
TI  - Fanconi anemia signaling and Mus81 cooperate to safeguard development and
      crosslink repair.
AB  - Individuals with Fanconi anemia (FA) are susceptible to bone marrow failure,
      congenital abnormalities, cancer predisposition and exhibit defective DNA
      crosslink repair. The relationship of this repair defect to disease traits
      remains unclear, given that crosslink sensitivity is recapitulated in FA mouse
      models without most of the other disease-related features. Mice deficient in
      Mus81 are also defective in crosslink repair, yet MUS81 mutations have not been
      linked to FA. Using mice deficient in both Mus81 and the FA pathway protein
      FancC, we show both proteins cooperate in parallel pathways, as concomitant loss
      of FancC and Mus81 triggered cell-type-specific proliferation arrest, apoptosis
      and DNA damage accumulation in utero. Mice deficient in both FancC and Mus81 that
      survived to birth exhibited growth defects and an increased incidence of
      congenital abnormalities. This cooperativity of FancC and Mus81 in developmental
      outcome was also mirrored in response to crosslink damage and chromosomal
      integrity. Thus, our findings reveal that both pathways safeguard against DNA
      damage from exceeding a critical threshold that triggers proliferation arrest and
      apoptosis, leading to compromised in utero development. 

PMID- 25056315
TI  - The structural code of cyanobacterial genomes.
AB  - A periodic bias in nucleotide frequency with a period of about 11 bp is
      characteristic for bacterial genomes. This signal is commonly interpreted to
      relate to the helical pitch of negatively supercoiled DNA. Functions in
      supercoiling-dependent RNA transcription or as a 'structural code' for DNA
      packaging have been suggested. Cyanobacterial genomes showed especially strong
      periodic signals and, on the other hand, DNA supercoiling and supercoiling
      dependent transcription are highly dynamic and underlie circadian rhythms of
      these phototrophic bacteria. Focusing on this phylum and dinucleotides, we find
      that a minimal motif of AT-tracts (AT2) yields the strongest signal. Strong
      genome-wide periodicity is ancestral to a clade of unicellular and polyploid
      species but lost upon morphological transitions into two baeocyte-forming and a
      symbiotic species. The signal is intermediate in heterocystous species and weak
      in monoploid picocyanobacteria. A pronounced 'structural code' may support
      efficient nucleoid condensation and segregation in polyploid cells. The major
      source of the AT2 signal are protein-coding regions, where it is encoded
      preferentially in the first and third codon positions. The signal shows only few
      relations to supercoiling-dependent and diurnal RNA transcription in
      Synechocystis sp. PCC 6803. Strong and specific signals in two distinct
      transposons suggest roles in transposase transcription and transpososome
      formation. 

PMID- 25056316
TI  - Global absolute quantification reveals tight regulation of protein expression in
      single Xenopus eggs.
AB  - While recent developments in genomic sequencing technology have enabled
      comprehensive transcriptome analyses of single cells, single cell proteomics has
      thus far been restricted to targeted studies. Here, we perform global absolute
      protein quantification of fertilized Xenopus laevis eggs using mass spectrometry
      based proteomics, quantifying over 5800 proteins in the largest single cell
      proteome characterized to date. Absolute protein amounts in single eggs are
      highly consistent, thus indicating a tight regulation of global protein
      abundance. Protein copy numbers in single eggs range from tens of thousands to
      ten trillion copies per cell. Comparison between the single-cell proteome and
      transcriptome reveal poor expression correlation. Finally, we identify 439
      proteins that significantly change in abundance during early embryogenesis.
      Downregulated proteins include ribosomal proteins and upregulated proteins
      include basal transcription factors, among others. Many of these proteins do not
      show regulation at the transcript level. Altogether, our data reveal that the
      transcriptome is a poor indicator of the proteome and that protein levels are
      tightly controlled in X. laevis eggs. 

PMID- 25056317
TI  - A-to-I editing in the miRNA seed region regulates target mRNA selection and
      silencing efficiency.
AB  - Hydrolytic deamination of adenosine to inosine (A-to-I) by adenosine deaminases
      acting on RNA (ADARs) is a post-transcriptional modification which results in a
      discrepancy between genomic DNA and the transcribed RNA sequence, thus
      contributing to the diversity of the transcriptome. Inosine preferentially base
      pairs with cytidine, meaning that A-to-I modifications in the mRNA sequences may
      be observed as A-to-G substitutions by the protein-coding machinery. Genome-wide
      studies have revealed that the majority of editing events occur in non-coding RNA
      sequences, but little is known about their functional meaning. MiRNAs are small
      non-coding RNAs that regulate the expression of target mRNAs with
      complementarities to their seed region. Here, we confirm that A-to-I editing in
      the miRNA seed duplex globally reassigns their target mRNAs in vivo, and reveal
      that miRNA containing inosine in the seed region exhibits a different degree of
      silencing efficiency compared to the corresponding miRNA with guanosine at the
      same position. The difference in base-pairing stability, deduced by melting
      temperature measurements, between seed-target duplexes containing either C:G or
      I:C pairs may account for the observed silencing efficiency. These findings
      unequivocally show that C:G and I:C pairs are biologically different in terms of
      gene expression regulation by miRNAs. 

PMID- 25056318
TI  - 5' isomiR variation is of functional and evolutionary importance.
AB  - We have sequenced miRNA libraries from human embryonic, neural and foetal
      mesenchymal stem cells. We report that the majority of miRNA genes encode mature
      isomers that vary in size by one or more bases at the 3' and/or 5' end of the
      miRNA. Northern blotting for individual miRNAs showed that the proportions of
      isomiRs expressed by a single miRNA gene often differ between cell and tissue
      types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo
      and were active in luciferase assays, indicating that they are functional.
      Bioinformatics analysis predicts substantial differences in targeting between
      miRNAs with minor 5' differences and in support of this we report that a 5'
      isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but
      lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use
      of isomiR-specific sponges. Our analysis of the miRGator database indicates that
      a small percentage of human miRNA genes express isomiRs as the dominant
      transcript in certain cell types and analysis of miRBase shows that 5' isomiRs
      have replaced canonical miRNAs many times during evolution. This strongly
      indicates that isomiRs are of functional importance and have contributed to the
      evolution of miRNA genes. 

PMID- 25056319
TI  - Simulations of DNA topoisomerase 1B bound to supercoiled DNA reveal changes in
      the flexibility pattern of the enzyme and a secondary protein-DNA binding site.
AB  - Human topoisomerase 1B has been simulated covalently bound to a negatively
      supercoiled DNA minicircle, and its behavior compared to the enzyme bound to a
      simple linear DNA duplex. The presence of the more realistic supercoiled
      substrate facilitates the formation of larger number of protein-DNA interactions
      when compared to a simple linear duplex fragment. The number of protein-DNA
      hydrogen bonds doubles in proximity to the active site, affecting all of the
      residues in the catalytic pentad. The clamp over the DNA, characterized by the
      salt bridge between Lys369 and Glu497, undergoes reduced fluctuations when bound
      to the supercoiled minicircle. The linker domain of the enzyme, which is
      implicated in the controlled relaxation of superhelical stress, also displays an
      increased number of contacts with the minicircle compared to linear DNA. Finally,
      the more complex topology of the supercoiled DNA minicircle gives rise to a
      secondary DNA binding site involving four residues located on subdomain III. The
      simulation trajectories reveal significant changes in the interactions between
      the enzyme and the DNA for the more complex DNA topology, which are consistent
      with the experimental observation that the protein has a preference for binding
      to supercoiled DNA. 

PMID- 25056320
TI  - VNTRseek-a computational tool to detect tandem repeat variants in high-throughput
      sequencing data.
AB  - DNA tandem repeats (TRs) are ubiquitous genomic features which consist of two or
      more adjacent copies of an underlying pattern sequence. The copies may be
      identical or approximate. Variable number of tandem repeats or VNTRs are
      polymorphic TR loci in which the number of pattern copies is variable. In this
      paper we describe VNTRseek, our software for discovery of minisatellite VNTRs
      (pattern size >= 7 nucleotides) using whole genome sequencing data. VNTRseek maps
      sequencing reads to a set of reference TRs and then identifies putative VNTRs
      based on a discrepancy between the copy number of a reference and its mapped
      reads. VNTRseek was used to analyze the Watson and Khoisan genomes (454
      technology) and two 1000 Genomes family trios (Illumina). In the Watson genome,
      we identified 752 VNTRs with pattern sizes ranging from 7 to 84 nt. In the
      Khoisan genome, we identified 2572 VNTRs with pattern sizes ranging from 7 to 105
      nt. In the trios, we identified between 2660 and 3822 VNTRs per individual and
      found nearly 100% consistency with Mendelian inheritance. VNTRseek is, to the
      best of our knowledge, the first software for genome-wide detection of
      minisatellite VNTRs. It is available at http://orca.bu.edu/vntrseek/. 

PMID- 25056321
TI  - The bacterial antitoxin HipB establishes a ternary complex with operator DNA and
      phosphorylated toxin HipA to regulate bacterial persistence.
AB  - Nearly all bacteria exhibit a type of phenotypic growth described as persistence
      that is thought to underlie antibiotic tolerance and recalcitrant chronic
      infections. The chromosomally encoded high-persistence (Hip) toxin-antitoxin
      proteins HipASO and HipBSO from Shewanella oneidensis, a proteobacterium with
      unusual respiratory capacities, constitute a type II toxin-antitoxin protein
      module. Here we show that phosphorylated HipASO can engage in an unexpected
      ternary complex with HipBSO and double-stranded operator DNA that is distinct
      from the prototypical counterpart complex from Escherichia coli. The structure of
      HipBSO in complex with operator DNA reveals a flexible C-terminus that is
      sequestered by HipASO in the ternary complex, indicative of its role in binding
      HipASO to abolish its function in persistence. The structure of HipASO in complex
      with a non-hydrolyzable ATP analogue shows that HipASO autophosphorylation is
      coupled to an unusual conformational change of its phosphorylation loop. However,
      HipASO is unable to phosphorylate the translation factor Elongation factor Tu,
      contrary to previous reports, but in agreement with more recent findings. Our
      studies suggest that the phosphorylation state of HipA is an important factor in
      persistence and that the structural and mechanistic diversity of HipAB modules as
      regulatory factors in bacterial persistence is broader than previously thought. 

PMID- 25056322
TI  - An efficient and sensitive method for preparing cDNA libraries from scarce
      biological samples.
AB  - The preparation and high-throughput sequencing of cDNA libraries from samples of
      small RNA is a powerful tool to quantify known small RNAs (such as microRNAs) and
      to discover novel RNA species. Interest in identifying the small RNA repertoire
      present in tissues and in biofluids has grown substantially with the findings
      that small RNAs can serve as indicators of biological conditions and disease
      states. Here we describe a novel and straightforward method to clone cDNA
      libraries from small quantities of input RNA. This method permits the generation
      of cDNA libraries from sub-picogram quantities of RNA robustly, efficiently and
      reproducibly. We demonstrate that the method provides a significant improvement
      in sensitivity compared to previous cloning methods while maintaining
      reproducible identification of diverse small RNA species. This method should have
      widespread applications in a variety of contexts, including biomarker discovery
      from scarce samples of human tissue or body fluids. 

PMID- 25056323
TI  - Population analysis of Streptococcus suis isolates from slaughtered swine by use
      of minimum core genome sequence typing.
AB  - Streptococcus suis, an important zoonotic pathogen, is a highly diverse species
      with only a subset of strains that cause disease in humans. Our previous study
      proposed a minimum core genome (MCG) sequence typing method and defined seven MCG
      groups, with MCG group 1 as the prevalent group causing human infections. In this
      study, we identified a set of 10 single nucleotide polymorphisms (SNPs)
      distributed in six genes that were used to identify the seven MCG groups. The 10
      SNPs were typed for 179 S. suis isolates collected from slaughtered pigs. The
      most prevalent groups among the tested isolates were MCG groups 6 and 7. Most of
      the isolates (147/179) were genotyped as mrp negative, epf negative, sly
      negative, and CDS2157 positive. The 179 isolates were also typed by multilocus
      sequence typing (MLST) and divided into 115 sequence types (STs), 111 of which
      were new. The 6 serotypes (29, 11, 5, 12, 30, and 2) represented 72.3% of the
      serotyped isolates. Our data show that the typing assay facilitates the
      application of genome data to the surveillance of S. suis. 

PMID- 25056324
TI  - Using crude whole-genome assemblies of Neisseria gonorrhoeae as a platform for
      strain analysis: clonal spread of gonorrhea infection in Saskatchewan, Canada.
AB  - Using crude whole-genome assemblies, we analyzed 25 isolates of Neisseria
      gonorrhoeae by using a high-resolution single nucleotide polymorphism (SNP)
      approach for nine housekeeping genes, characterizing penA alleles, and
      antimicrobial susceptibility phenotypes coupled with population structure
      analysis. Two clonal complexes, characterized by their spatial and geographical
      persistence, were identified. In addition, the clonal spread of penicillin
      resistant/intermediate phenotypes and a novel introduction of the azithromycin
      resistance phenotype in Saskatchewan, Canada, were ascertained using this method.

PMID- 25056325
TI  - Detection of Mycobacterium leprae by PCR testing of sputa from a patient with
      pulmonary cryptococcus coinfection in northern Australia.
AB  - A case of fever, sepsis, and chest lesions evident on a computed tomography scan
      of an indigenous man in northern Australia following burns to the feet is
      described. Sputum PCR testing revealed Mycobacterium leprae, and a fine-needle
      aspirate of the chest lesions demonstrated Cryptococcus coinfection. 

PMID- 25056326
TI  - Using genomics to standardize population analysis profile-area under the curve
      ratio for vancomycin-intermediate Staphylococcus aureus.

PMID- 25056327
TI  - Lumbar discitis caused by Clostridium perfringens.
AB  - We report here a rare case of chronic lumbar discitis caused by Clostridium
      perfringens in an elderly patient that was treated with a combination of beta
      lactams and clindamycin. Molecular analysis performed on the strain revealed an
      unusual toxin gene pattern. 

PMID- 25056328
TI  - Comparison of amplicor and GeneXpert MTB/RIF tests for diagnosis of tuberculous
      meningitis.
AB  - There are no data about the comparative accuracy of commercially available
      nucleic acid amplification tests (GeneXpert MTB/RIF and Roche Amplicor) for the
      diagnosis of tuberculous meningitis (TBM). A total of 148 patients with suspected
      TBM were evaluated, and cultures served as the reference standard. The
      sensitivities and specificities (95% confidence interval [CI]) for the Amplicor
      and Xpert MTB/RIF tests were similar: 46 (31-60) versus 50 (33-67) and 99 (93
      100) and 94 (84-99), respectively. 

PMID- 25056329
TI  - Microbial typing by matrix-assisted laser desorption ionization-time of flight
      mass spectrometry: do we need guidance for data interpretation?
AB  - The integration of matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF MS) in clinical microbiology has revolutionized
      species identification of bacteria, yeasts, and molds. However, beyond
      straightforward identification, the method has also been suggested to have the
      potential for subspecies-level or even type-level epidemiological analyses. This
      minireview explores MALDI-TOF MS-based typing, which has already been performed
      on many clinically relevant species. We discuss the limits of the method's
      resolution and we suggest interpretative criteria allowing valid comparison of
      strain-specific data. We conclude that guidelines for MALDI-TOF MS-based typing
      can be developed along the same lines as those used for the interpretation of
      data from pulsed-field gel electrophoresis (PFGE). 

PMID- 25056330
TI  - Genome sequencing of Mycobacterium abscessus isolates from patients in the united
      states and comparisons to globally diverse clinical strains.
AB  - Nontuberculous mycobacterial infections caused by Mycobacterium abscessus are
      responsible for a range of disease manifestations from pulmonary to skin
      infections and are notoriously difficult to treat, due to innate resistance to
      many antibiotics. Previous population studies of clinical M. abscessus isolates
      utilized multilocus sequence typing or pulsed-field gel electrophoresis, but high
      resolution examinations of genetic diversity at the whole-genome level have not
      been well characterized, particularly among clinical isolates derived in the
      United States. We performed whole-genome sequencing of 11 clinical M. abscessus
      isolates derived from eight U.S. patients with pulmonary nontuberculous
      mycobacterial infections, compared them to 30 globally diverse clinical isolates,
      and investigated intrapatient genomic diversity and evolution. Phylogenomic
      analyses revealed a cluster of closely related U.S. and Western European M.
      abscessus subsp. abscessus isolates that are genetically distinct from other
      European isolates and all Asian isolates. Large-scale variation analyses
      suggested genome content differences of 0.3 to 8.3%, relative to the reference
      strain ATCC 19977(T). Longitudinally sampled isolates showed very few single
      nucleotide polymorphisms and correlated genomic deletion patterns, suggesting
      homogeneous infection populations. Our study explores the genomic diversity of
      clinical M. abscessus strains from multiple continents and provides insight into
      the genome plasticity of an opportunistic pathogen. 

PMID- 25056332
TI  - Comparison of two commercial real-time PCR assays for detection of dengue virus
      in patient serum samples.
AB  - This study evaluated and compared the performance of two real-time PCR assays
      using nested reverse transcription (RT)-PCR as the reference method. Among 117
      nested RT-PCR-positive cases, the abTES DEN 5 qPCR kit detected 97.4% of dengue
      virus (DENV) infections, while the innuDETECT Dengue TwoStep assay did so for
      44.4%. Sensitivity varied by infecting serotype and the stage of infection. The
      abTES kit has the potential to replace nested RT-PCR for the rapid diagnosis of
      DENV infection. 

PMID- 25056331
TI  - Evaluation of 16S rRNA gene PCR sensitivity and specificity for diagnosis of
      prosthetic joint infection: a prospective multicenter cross-sectional study.
AB  - There is no standard method for the diagnosis of prosthetic joint infection
      (PJI). The contribution of 16S rRNA gene PCR sequencing on a routine basis
      remains to be defined. We performed a prospective multicenter study to assess the
      contributions of 16S rRNA gene assays in PJI diagnosis. Over a 2-year period, all
      patients suspected to have PJIs and a few uninfected patients undergoing primary
      arthroplasty (control group) were included. Five perioperative samples per
      patient were collected for culture and 16S rRNA gene PCR sequencing and one for
      histological examination. Three multicenter quality control assays were performed
      with both DNA extracts and crushed samples. The diagnosis of PJI was based on
      clinical, bacteriological, and histological criteria, according to Infectious
      Diseases Society of America guidelines. A molecular diagnosis was modeled on the
      bacteriological criterion (>= 1 positive sample for strict pathogens and >= 2 for
      commensal skin flora). Molecular data were analyzed according to the diagnosis of
      PJI. Between December 2010 and March 2012, 264 suspected cases of PJI and 35
      control cases were included. PJI was confirmed in 215/264 suspected cases, 192
      (89%) with a bacteriological criterion. The PJIs were monomicrobial (163 cases
      [85%]; staphylococci, n = 108; streptococci, n = 22; Gram-negative bacilli, n =
      16; anaerobes, n = 13; others, n = 4) or polymicrobial (29 cases [15%]). The
      molecular diagnosis was positive in 151/215 confirmed cases of PJI (143 cases
      with bacteriological PJI documentation and 8 treated cases without
      bacteriological documentation) and in 2/49 cases without confirmed PJI
      (sensitivity, 73.3%; specificity, 95.5%). The 16S rRNA gene PCR assay showed a
      lack of sensitivity in the diagnosis of PJI on a multicenter routine basis.

PMID- 25056333
TI  - False-positive results for rapid diagnostic tests for malaria in patients with
      rheumatoid factor.
AB  - Four different rapid diagnostic tests (RDTs) for malaria were evaluated by
      testing 82 healthy control patients, 89 Plasmodium vivax-infected patients, and
      92 rheumatoid factor (RF)-positive nonmalaria patients. The false-positive rate
      ranged from 2.2% to 13% in RF-positive patients. High RF levels are associated
      with malaria RDT false positivity. 

PMID- 25056334
TI  - Interspecies transfer of blaIMP-4 in a patient with prolonged colonization by IMP
      4-producing Enterobacteriaceae.
AB  - A patient was colonized by IMP-4-producing Enterobacter cloacae and Escherichia
      coli strains for 7 months. IMP-4-producing E. cloacae strains were first and last
      isolated at day 33 and at 8 months after admission, respectively. IMP-4-producing
      E. coli strains were first and last isolated at days 88 and 181 after admission,
      respectively. The E. cloacae and E. coli isolates shared identical genetic
      features in terms of blaIMP-4, blaTEM-1, qnrB2, aacA4, HI2 plasmids, and ISCR1.
      This study shows the first prolonged colonization with in vivo interspecies
      transfer of blaIMP-4. 

PMID- 25056335
TI  - Detection of respiratory viruses in sputum from adults by use of automated
      multiplex PCR.
AB  - Respiratory tract infections (RTI) frequently cause hospital admissions among
      adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat
      swabs (NTS) is useful for patient care by informing antiviral use and appropriate
      isolation. However, automated RT-PCR systems are not amenable to utilizing sputum
      due to its viscosity. We evaluated a simple method of processing sputum samples
      in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived
      sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI
      were evaluated. A subset of sputum samples positive for 10 common viruses by a
      uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum,
      swirled in 700 MUL of sterile water (dunk and swirl method) and tested by the
      FilmArray assay. Quantitative RT-PCR was performed on "dunked" sputum and NTS
      samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus
      OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of
      965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample
      positive for 105 subjects, including 35% (22/64) of influenza cases and
      significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus
      197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray
      assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT
      PCR revealed higher mean viral loads in dunked sputum samples compared to NTS
      samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011,
      respectively). The dunk and swirl method is a simple and practical method for
      reliably processing sputum samples in a fully automated PCR system. The higher
      viral loads in sputa may increase detection over NTS testing alone. 

PMID- 25056336
TI  - A woman with pain and weakness in both legs.

PMID- 25056337
TI  - COnsiderations of Nephrologists when SuggestIng Dialysis in Elderly patients with
      Renal failure (CONSIDER): a discrete choice experiment.
AB  - BACKGROUND: Nephrologists often face difficult decisions when recommending
      dialysis or non-dialysis (supportive) care for elderly patients, given the
      uncertainty around survival and the burden of dialysis. Discrete choice
      experiments (DCEs) mimic real-world decisions through simultaneous consideration
      of multiple variables. We aimed to determine the relative influence of patient
      characteristics on dialysis recommendations. METHODS: We conducted a DCE among
      Australasian nephrologists consisting of 12 scenarios of two patients (described
      in terms of age, gender, cognition, comorbidity, life expectancy, current quality
      of life (QOL), expected QOL with dialysis, social support, patient and family
      inclination). Nephrologists indicated which patient they preferred recommending
      dialysis for, or whether they preferred 'neither'. Mixed logit models determined
      the odds of recommending dialysis over no dialysis. Trade-offs between QOL and
      survival were calculated. RESULTS: A total of 159 nephrologists participated (34%
      aged 40-49 years, 62% male and 69% Caucasian). All patient characteristics except
      gender significantly affected the likelihood of dialysis recommendation.
      Nephrologists were more likely to recommend dialysis for patients with preserved
      cognition (odds ratio [OR]: 68.3; 95% confidence interval [CI]: 33.4-140.0),
      lower comorbidity (OR: 2.1; 95% CI: 1.1-4.1), increased life expectancy (OR: 2.8;
      95% CI: 2.1-3.7), high current QOL (OR: 2.8; 95% CI: 2.0-3.8) and positive
      patient and family dialysis inclination (OR: 27.5; 95% CI: 16.2-46.8 and OR: 2.0;
      95% CI: 1.3-3.3, respectively). Nephrologists aged >65 were more likely (OR:
      11.7; 95% CI: 1.8-77.2) to recommend dialysis. Nephrologists were willing to
      forgo 12 months of patient survival to avoid substantial QOL decrease with
      dialysis. CONCLUSION: Nephrologists avoided dialysis recommendation if it was
      expected to considerably reduce QOL. To inform elderly patients' dialysis
      decisions, systematic and longitudinal cognition and QOL evaluations are needed
      as well as better research into understanding patient preferences.

PMID- 25056338
TI  - Sex difference in leukocyte telomere length is ablated in opposite-sex co-twins.
AB  - BACKGROUND: In eutherian mammals and in humans, the female fetus may be
      masculinized while sharing the intra-uterine environment with a male fetus.
      Telomere length (TL), as expressed in leukocytes, is heritable and is longer in
      women than in men. The main determinant of leukocyte TL (LTL) is LTL at birth.
      However, LTL is modified by age-dependent attrition. METHODS: We studied LTL
      dynamics (LTL and its attrition) in adult same-sex (monozygotic, n = 268;
      dizygotic, n = 308) twins and opposite-sex (n = 144) twins. LTL was measured by
      Southern blots of the terminal restriction fragments. RESULTS: We observed that
      in same-sex (both monozygotic and dizygotic) twins, as reported in singletons,
      LTL was longer in females than in males [estimate +/- standard error (SE):163 +/-
      63 bp, P < 0.01]. However, in opposite-sex twins, female LTL was
      indistinguishable from that of males (-31 +/- 52 bp, P = 0.6), whereas male LTL
      was not affected. Findings were similar when the comparison was restricted to
      opposite-sex and same-sex dizygotic twins (females relative to males: same-sex:
      188 +/- 90 bp, P < 0.05; other-sex: -32 +/- 64 bp, P = 0.6). CONCLUSIONS: These
      findings are compatible with masculinization of the female fetus in opposite-sex
      twins. They suggest that the sex difference in LTL, seen in the general
      population, is largely determined in utero, perhaps by the intrauterine hormonal
      environment. Further studies in newborn twins are warranted to test this thesis.

PMID- 25056339
TI  - Does migration affect asthma, rhinoconjunctivitis and eczema prevalence? Global
      findings from the international study of asthma and allergies in childhood.
AB  - BACKGROUND: Immigrants to Westernized countries adopt the prevalence of allergic
      diseases of native populations, yet no data are available on immigrants to low
      income or low-disease prevalence countries. We investigated these questions using
      data from the International Study of Asthma and Allergies in Childhood. METHODS:
      Standardized questionnaires were completed by 13-14-year-old adolescents and by
      the parent/guardians of 6-7-year-old children. Questions on the symptom
      prevalence of asthma, rhinoconjunctivitis and eczema, and a wide range of factors
      postulated to be associated with these conditions, including birth in or not in
      the country and age at immigration, were asked. Odds ratios for risk of the three
      diseases according to immigration status were calculated using generalized linear
      mixed models. These were adjusted for: world region; language and gross national
      income; and individual risk factors including gender, maternal education,
      antibiotic and paracetamol use, maternal smoking, and diet. Effect modification
      by gross national income and by prevalence was examined. RESULTS: There were 326
      691 adolescents from 48 countries and 208 523 children from 31 countries.
      Immigration was associated with a lower prevalence of asthma, rhinoconjunctivitis
      and eczema in both age groups than among those born in the country studied, and
      this association was mainly confined to high-prevalence/affluent countries. This
      reduced risk was greater in those who had lived fewer years in the host country.
      CONCLUSIONS: Recent migration to high prevalence/affluent countries is associated
      with a lower prevalence of allergic diseases. The protective pre-migration
      environment quickly decreases with increasing time in the host country.

PMID- 25056341
TI  - Neil Bacon: Hates wasting a single moment.

PMID- 25056340
TI  - Modelling Gaucher disease progression: long-term enzyme replacement therapy
      reduces the incidence of splenectomy and bone complications.
AB  - Long-term complications and associated conditions of type 1 Gaucher Disease (GD)
      can include splenectomy, bone complications, pulmonary hypertension, Parkinson
      disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and
      reduces organomegaly. To study the effects of ERT on long-term complications and
      associated conditions, the course of Gaucher disease was modelled. 

PMID- 25056342
TI  - Diagnostic and predictive capability of routine laboratory tests for the
      diagnosis and staging of equine inflammatory disease.
AB  - BACKGROUND: A wide spectrum of laboratory tests is available to aid diagnosis and
      classification of equine inflammatory disease. OBJECTIVES: To compare diagnostic
      efficacy and combined predictive capability of the myeloperoxidase index (MPXI),
      and plasma fibrinogen, iron and serum amyloid A (SAA) concentrations for the
      diagnosis of inflammation. ANIMALS: Twenty-six hospitalized horses with systemic
      inflammation (SI), 114 with local inflammation (LI) and 61 healthy horses or
      those with noninflammatory disease (NI) were included. METHODS: A retrospective
      study was performed; clinicopathologic data from horses were compared between
      groups. Receiver-operator characteristic (ROC) curves were used to evaluate
      diagnostic efficacy; classification and regression tree analysis (CART) and
      logistic regression analysis were used to generate diagnostic algorithms.
      RESULTS: Horses with SI had significantly higher SAA than horses with LI (P =
      .007) and NI (P < .001) and lower iron concentrations than horses with LI (P <
      .001) and NI (P < .001). Fibrinogen concentration was higher in horses with
      inflammation than in those without inflammation (P = .002). There was no
      difference between the SI and LI groups. White blood cell count, neutrophil count
      and MPXI were similar between groups. SAA had the highest accuracy for diagnosing
      inflammation (area under ROC curve [AUC], 0.83 +/- 0.06) and iron and SAA
      concentration had the highest accuracy for differentiating SI from LI (AUC, 0.80
      +/- 0.09 and 0.73 +/- 0.10 respectively). Predictive modeling failed to generate
      useful algorithms and classification of cases was moderate. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Very high SAA and low iron concentrations may reflect SI,
      but diagnostic guidelines based on quantitative results of inflammatory markers
      could not be formulated.

PMID- 25056343
TI  - On-demand optical immobilization of Caenorhabditis elegans for high-resolution
      imaging and microinjection.
AB  - This paper describes a novel selective immobilization technique based on optical
      control of the sol-gel transition of thermoreversible Pluronic gel, which
      provides a simple, versatile, and biocompatible approach for high-resolution
      imaging and microinjection of Caenorhabditis elegans. 

PMID- 25056344
TI  - Targeted delivery of solutes and oxygen in the renal medulla: role of microvessel
      architecture.
AB  - Renal medullary function is characterized by corticopapillary concentration
      gradients of various molecules. One example is the generally decreasing axial
      gradient in oxygen tension (Po2). Another example, found in animals in the
      antidiuretic state, is a generally increasing axial solute gradient, consisting
      mostly of NaCl and urea. This osmolality gradient, which plays a principal role
      in the urine concentrating mechanism, is generally considered to involve
      countercurrent multiplication and countercurrent exchange, although the
      underlying mechanism is not fully understood. Radial oxygen and solute gradients
      in the transverse dimension of the medullary parenchyma have been hypothesized to
      occur, although strong experimental evidence in support of these gradients
      remains lacking. This review considers anatomic features of the renal medulla
      that may impact the formation and maintenance of oxygen and solute gradients. A
      better understanding of medullary architecture is essential for more clearly
      defining the compartment-to-compartment flows taken by fluid and molecules that
      are important in producing axial and radial gradients. Preferential interactions
      between nephron and vascular segments provide clues as to how tubular and
      interstitial oxygen flows contribute to safeguarding active transport pathways in
      renal function in health and disease. 

PMID- 25056345
TI  - To cleave or not to cleave: role of ADAM17 in cell proliferation in PKD.

PMID- 25056346
TI  - Regulation of proximal tubular cell differentiation and proliferation in primary
      culture by matrix stiffness and ECM components.
AB  - To explore whether matrix stiffness affects cell differentiation, proliferation,
      and transforming growth factor (TGF)-beta1-induced epithelial-mesenchymal
      transition (EMT) in primary cultures of mouse proximal tubular epithelial cells
      (mPTECs), we used a soft matrix made from monomeric collagen type I-coated
      polyacrylamide gel or matrigel (MG). Both kinds of soft matrix benefited primary
      mPTECs to retain tubular-like morphology with differentiation and growth arrest
      and to evade TGF-beta1-induced EMT. However, the potent effect of MG on mPTEC
      differentiation was suppressed by glutaraldehyde-induced cross-linking and
      subsequently stiffening MG or by an increasing ratio of collagen in the soft
      mixed gel. Culture media supplemented with MG also helped mPTECs to retain
      tubular-like morphology and a differentiated phenotype on stiff culture dishes as
      soft MG did. We further found that the protein level and activity of ERK were
      scaled with the matrix stiffness. U-0126, a MEK inhibitor, abolished the stiff
      matrix-induced dedifferentiation and proliferation. These data suggest that the
      ERK signaling pathway plays a vital role in matrix stiffness-regulated cell
      growth and differentiation. Taken together, both compliant property and specific
      MG signals from the matrix are required for the regulation of epithelial
      differentiation and proliferation. This study provides a basic understanding of
      how physical and chemical cues derived from the extracellular matrix regulate the
      physiological function of proximal tubules and the pathological development of
      renal fibrosis. 

PMID- 25056347
TI  - Expression of a novel stress-inducible protein, sestrin 2, in rat glomerular
      parietal epithelial cells.
AB  - Sestrin 2, initially identified as a p53 target protein, accumulates in cells
      exposed to stress and inhibits mammalian target of rapamycin (mTOR) signaling. In
      normal rat kidneys, sestrin 2 was selectively expressed in parietal epithelial
      cells (PECs), identified by the marker protein gene product 9.5. In adriamycin
      nephropathy, sestrin 2 expression decreased in PECs on day 14, together with
      increased expression of phosphorylated S6 ribosomal protein (P-S6RP), a
      downstream target of mTOR. Sestrin 2 expression was markedly decreased on day 42,
      coinciding with glomerulosclerosis and severe periglomerular fibrosis. In
      puromycin aminonucleoside nephropathy, decreased sestrin 2 expression, increased
      P-S6RP expression, and periglomerular fibrosis were observed on day 9, when
      massive proteinuria developed. These changes were transient and nearly normalized
      by day 28. In crescentic glomerulonephritis, sestrin 2 expression was not
      detected in cellular crescents, whereas P-S6RP increased. In conditionally
      immortalized cultured PECs, the forced downregulation of sestrin 2 by short
      hairpin RNA resulted in increased expression of P-S6RP and increased apoptosis.
      These data suggest that sestrin 2 is involved in PEC homeostasis by regulating
      the activity of mTOR. In addition, sestrin 2 could be a novel marker of PECs, and
      decreased expression of sestrin 2 might be a marker of PEC injury. 

PMID- 25056348
TI  - Complement-mediated glomerular injury is reduced by inhibition of protein
      tyrosine phosphatase 1B.
AB  - The unfolded protein response and endoplasmic reticulum-associated degradation
      (ERAD) contribute to injury in renal glomerular diseases, including those
      mediated by complement C5b-9. In the present study, we address the role of
      protein-tyrosine phosphatase 1B (PTP1B) in complement-mediated glomerular injury
      and ERAD. In glomerular epithelial cells (GECs)/podocytes and PTP1B-deficient
      mouse embryonic fibroblasts exposed to complement, inhibition/deletion of PTP1B
      reduced ERAD, as monitored by the ERAD reporter CD3delta. Overexpression of PTP1B
      produced an effect similar to PTP1B deficiency on ERAD in complement-treated
      GECs. Complement-mediated cytotoxicity was reduced after PTP1B overexpression and
      tended to be reduced after PTP1B inhibition. PTP1B enhanced the induction of
      certain ERAD components via the inositol-requiring-1alpha branch of the unfolded
      protein response. PTP1B knockout mice with anti-glomerular basement membrane
      glomerulonephritis had decreased proteinuria and showed less podocyte loss and
      endoplasmic reticulum dysfunction compared with wild-type littermates. These
      results imply that endogenous levels of PTP1B are tightly regulated and that both
      overexpression and inhibition can affect ERAD. The cytoprotective effects of
      PTP1B deletion in cultured cells and in anti-glomerular basement membrane
      nephritis suggest that PTP1B may potentially be a therapeutic target in
      complement-mediated diseases. 

PMID- 25056349
TI  - Renal PKC-epsilon deficiency attenuates acute kidney injury and ischemic
      allograft injury via TNF-alpha-dependent inhibition of apoptosis and
      inflammation.
AB  - Acute kidney injury (AKI) increases the risk of morbidity and mortality after
      major surgery and transplantation. We investigated the effect of PKC-epsilon
      deficiency on AKI and ischemic allograft damage after kidney transplantation. PKC
      epsilon-deficient and wild type (WT) control mice were subjected to 35 min of
      renal pedicle clamping to induce AKI. PKC-epsilon deficiency was associated with
      a marked improvement in survival and an attenuated loss of kidney function.
      Furthermore, functional MRI experiments revealed better renal perfusion in PKC
      epsilon-deficient mice than in WT mice one day after IRI. Acute tubular necrosis
      and neutrophil infiltration were markedly reduced in PKC-epsilon-deficient mice.
      To determine whether this resistance to ischemia-reperfusion injury resulted from
      changes in local renal cells or infiltrating leukocytes, we studied a life
      supporting renal transplant model of ischemic graft injury. We transplanted
      kidneys from H(2b) PKC-epsilon-deficient mice (129/SV) and their corresponding WT
      littermates into major histocompatibility complex-incompatible H(2d) recipients
      (BALB/c) and induced ischemic graft injury by prolonged cold ischemia time.
      Recipients of WT allografts developed severe renal failure and died within 10
      days of transplantation. Recipients of PKC-epsilon-deficient allografts had
      better renal function and survival; they had less generation of ROS and
      upregulation of proinflammatory proteins (i.e., ICAM-1, inducible nitric oxide
      synthase, and TNF-alpha) and showed less tubular epithelial cell apoptosis and
      inflammation in their allografts. These data suggest that local renal PKC-epsilon
      expression mediates proapoptotic and proinflammatory signaling and that an
      inhibitor of PKC-epsilon signaling could be used to prevent hypoxia-induced AKI. 

PMID- 25056350
TI  - Extrarenal citrulline disposal in mice with impaired renal function.
AB  - The endogenous synthesis of arginine, a semiessential amino acid, relies on the
      production of citrulline by the gut and its conversion into arginine by the
      kidney in what has been called the "intestinal-renal axis" for arginine
      synthesis. Although the kidney is the main site for citrulline disposal, it only
      accounts for ~60-70% of the citrulline produced. Because the only known fate for
      citrulline is arginine synthesis and the enzymes that catalyze this reaction are
      widespread among body tissues, we hypothesized that citrulline can be utilized
      directly by tissues to meet, at least partially, their arginine needs. To test
      this hypothesis, we used stable and radioactive tracers in conscious, partially
      nephrectomized (1/2 and 5/6) and anesthetized acutely kidney-ligated mouse
      models. Nephrectomy increased plasma citrulline concentration but did not affect
      citrulline synthesis rates, thus reducing its clearance. Nephrectomy (5/6)
      reduced the amount of citrulline accounted for as plasma arginine from 88 to 42%.
      Acute kidney ligation increased the half-life and mean retention time of
      citrulline. Whereas the rate of citrulline conversion into plasma arginine was
      reduced, it was not eliminated. In addition, we observed direct utilization of
      citrulline for arginine synthesis and further incorporation into tissue protein
      in kidney-ligated mice. These observations indicate that a fraction of the
      citrulline produced is utilized directly by multiple tissues to meet their
      arginine needs and that extrarenal sites contribute to plasma arginine.
      Furthermore, when the interorgan synthesis of arginine is impaired, these
      extrarenal sites are able to increase their rate of citrulline utilization.

PMID- 25056351
TI  - Inhibition of smooth muscle force generation by focal adhesion kinase inhibitors
      in the hyperplastic human prostate.
AB  - Smooth muscle contraction may be critical for lower urinary tract symptoms (LUTS)
      in patients with benign prostate hyperplasia and requires stable anchorage of the
      cytoskeleton to the cell membrane. These connections are regulated by focal
      adhesion kinase (FAK). Here, we addressed the involvement of FAK in the
      regulation of smooth muscle contraction in hyperplastic human prostate tissues.
      Prostate tissues were obtained from radical prostatectomy. Expression of FAK and
      focal adhesion proteins was assessed by Western blot analysis and
      immunohistochemical stainings. Effects of the FAK inhibitors PF-573228 and Y-11
      on contraction of prostate strips were examined in the organ bath. Expression of
      FAK and focal adhesion proteins (integrin-5alpha, paxilin, and c-Src) was
      detected by Western blot analysis in prostate samples. By double
      immunofluorescence staining with calponin and pan-cytokeratin, expression of FAK
      was observed in stromal and epithelial cells. Immunoreactivity for FAK
      colocalized with integrin-5alpha, paxilin, talin, and c-Src. Stimulation of
      prostate tissues with the alpha1-adrenergic agonist phenylephrine increased the
      phosphorylation state of FAK at Tyr397 and Tyr925 with different kinetics, which
      was blocked by the alpha1-adrenoceptor antagonist tamsulosin. Norepinephrine and
      phenylephrine induced concentration-dependent contractions of prostate strips.
      Both FAK inhibitors PF-573228 and Y-11 significantly inhibited norepinephrine-
      and phenylephrine-induced contractions. Finally, PF-573228 and Y-11 inhibited
      contractions induced by electric field stimulation, which was significant at the
      highest frequency. In conclusion, alpha1-adrenergic smooth muscle contraction or
      its regulation involves FAK in the human prostate. Consequently, FAK may be
      involved in the pathophysiology of LUTS and in current or future LUTS therapies.

PMID- 25056352
TI  - Somatic modulation of spinal reflex bladder activity mediated by nociceptive
      bladder afferent nerve fibers in cats.
AB  - The goal of the present study was to determine if supraspinal pathways are
      necessary for inhibition of bladder reflex activity induced by activation of
      somatic afferents in the pudendal or tibial nerve. Cats anesthetized with alpha
      chloralose were studied after acute spinal cord transection at the thoracic
      T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder,
      activate nociceptive afferent C-fibers, and trigger spinal reflex bladder
      contractions (amplitude: 19.3 +/- 2.9 cmH2O). Hexamethonium (a ganglionic
      blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the
      reflex bladder contractions to 8.5 +/- 1.9 cmH2O. Injection of lidocaine (2%, 1-2
      ml) into the sacral spinal cord or transection of the sacral spinal roots and
      spinal cord further reduced the contraction amplitude to 4.2 +/- 1.3 cmH2O.
      Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at
      10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation
      (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40
      Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber
      mediated spinal reflex bladder contractions can occur at the spinal level in the
      absence of supraspinal pathways, but TNS inhibition requires supraspinal
      pathways. In addition, this study shows, for the first time, that after acute
      spinal cord transection reflex bladder contractions can be triggered by
      activating nociceptive bladder afferent C-fibers using acetic acid irritation.
      Understanding the sites of action for PNS or TNS inhibition is important for the
      clinical application of pudendal or tibial neuromodulation to treat bladder
      dysfunctions. 

PMID- 25056353
TI  - Nanotechnology and adeno-associated virus-based decorin gene therapy ameliorates
      peritoneal fibrosis.
AB  - Peritoneal dialysis (PD) is a life-sustaining therapy for end-stage renal disease
      (ESRD), used by 10-15% of the dialysis population worldwide. Peritoneal fibrosis
      (PF) is a known complication of long-term PD and frequently follows episodes of
      peritonitis, rendering the peritoneal membrane inadequate for dialysis.
      Transforming growth factor (TGF)-beta is an inducer of fibrosis in several
      tissues and organs, and its overexpression has been correlated with PF. Animal
      models of peritonitis have shown an increase in expression of TGF-beta in the
      peritoneal tissue. Decorin, a proteoglycan and component of the extracellular
      matrix, inactivates TGF-beta, consequently reducing fibrosis in many tissues.
      Recently, gold nanoparticles (GNP) have been used for drug delivery in a variety
      of settings. In the present study, we tested the possibility that GNP-delivered
      decorin gene therapy ameliorates zymosan-mediated PF. We created a PF model using
      zymosan-induced peritonitis. Rats were treated with no decorin, GNP-decorin, or
      adeno-associated virus-decorin (AAV-decorin) and compared with controls. Tissue
      samples were then stained for Masson's trichrome, enface silver, and hematoxylin
      and eosin, and immunohistochemistry was carried out with antibodies to TGF-beta1,
      alpha-smooth muscle actin (alpha-SMA), and VEGF. Animals which were treated with
      GNP-decorin and AAV-decorin gene therapy had significant reductions in PF
      compared with untreated animals. Compared with untreated animals, the treated
      animals had better preserved peritoneal mesothelial cell size, a significant
      decrease in peritoneal thickness, and decreased alpha-SMA. Quantitative PCR
      measurements showed a significant decrease in the peritoneal tissue levels of
      alpha-SMA, TGF-beta, and VEGF in treated vs. untreated animals. This study shows
      that both GNP-delivered and AAV-mediated decorin gene therapies significantly
      decrease PF in vivo in a rodent model. This approach has important clinical
      translational potential in providing a therapeutic strategy to prevent PF in PD
      patients. 

PMID- 25056354
TI  - A knowledge base of vasopressin actions in the kidney.
AB  - Biological information is growing at a rapid pace, making it difficult for
      individual investigators to be familiar with all information that is relevant to
      their own research. Computers are beginning to be used to extract and curate
      biological information; however, the complexity of human language used in
      research papers continues to be a critical barrier to full automation of
      knowledge extraction. Here, we report a manually curated knowledge base of
      vasopressin actions in renal epithelial cells that is designed to be readable
      either by humans or by computer programs using natural language processing
      algorithms. The knowledge base consists of three related databases accessible at
      https://helixweb.nih.gov/ESBL/TinyUrls/Vaso_portal.html. One of the component
      databases reports vasopressin actions on individual proteins expressed in renal
      epithelia, including effects on phosphorylation, protein abundances, protein
      translocation from one subcellular compartment to another, protein-protein
      binding interactions, etc. The second database reports vasopressin actions on
      physiological measures in renal epithelia, and the third reports specific mRNA
      species whose abundances change in response to vasopressin. We illustrate the
      application of the knowledge base by using it to generate a protein kinase
      network that connects vasopressin binding in collecting duct cells to
      physiological effects to regulate the water channel protein aquaporin-2. 

PMID- 25056355
TI  - Renal MODY-fier genes.

PMID- 25056356
TI  - The challenges of interventional trials in fetal therapy.

PMID- 25056357
TI  - Bowel opacification in a very low weight born infant due to maternal
      administration of iodinated contrast agent.

PMID- 25056358
TI  - Synthetic particles as contaminants in German beers.
AB  - A total of 24 German beer brands was analysed for the contents of microplastic
      fibres, fragments and granular material. In all cases contamination was found.
      Counts ranged from 2 to 79 fibres L(-1), from 12 to 109 fragments L(-1) and from
      2 to 66 granules L(-1). The results show a high variability between individual
      samples and samples from different production dates. Possible sources of this
      contamination with foreign materials are discussed.

PMID- 25056359
TI  - Flavin-catalyzed aerobic oxidation of sulfides and thiols with formic
      acid/triethylamine.
AB  - An efficient and practical catalytic method for the aerobic oxidative
      transformation of sulfides into sulfoxides, and thiols into disulfides with
      formic acid/TEA in the presence of a new, readily available, and stable flavin
      catalyst 5d is described.

PMID- 25056360
TI  - Structure, photochemistry and applications of metal-doped polyoxotitanium
      alkoxide cages.
AB  - Metal-doped polyoxotitanium cages (M-POTs) of the type [TixOy(OR)zMnXm] (M = a
      main group, transition metal or lanthanide; X = an anion such as a halide) can be
      regarded as molecular fragments of metal-doped TiO2. As such M-POTs can be used
      as structural models for the inclusion of metal ions into the TiO2 lattice and
      the ways in which well-defined microstructural changes affect photo-induced hole
      electron separation. They are also potential organically-soluble redox-catalysts
      for a range of organic transformations and have been shown to be useful single
      source precursors for the deposition of metal-doped TiO2. The applications of M
      POTs as molecular precursors to metal-doped TiO2 offers a high degree of atomic
      control in the low temperature fabrication of photocatalytic thin films, which
      have applications in pollution control and water splitting. This perspective
      highlights the structural trends in M-POTs, their electronic behaviour and their
      applications as single-source precursors, looking at current and future trends in
      the development of inorganic precursors for device applications. 

PMID- 25056361
TI  - Critical analysis of compositions and protective efficacies of oral killed
      cholera vaccines.
AB  - Two cholera vaccines, sold as Shanchol and Dukoral, are currently available. This
      review presents a critical analysis of the protective efficacies of these
      vaccines. Children under 5 years of age are very vulnerable to cholera and
      account for the highest incidence of cholera cases and more than half of the
      resulting deaths. Both Shanchol and Dukoral are two-spaced-dose oral vaccines
      comprising large numbers of killed cholera bacteria. The former contains Vibrio
      cholerae O1 and O139 cells, and the latter contains V. cholerae O1 cells with the
      recombinant B subunit of cholera toxin. In a field trial in Kolkata (India),
      Shanchol, the preferred vaccine, protected 45% of the test subjects in all of the
      age groups and only 17% of the children under 5 years of age during the first
      year of surveillance. In a field trial in Peru, two spaced doses of Dukoral
      offered negative protection in children under 5 years of age and little
      protection (15%) in vaccinees over 6 years of age during the first year of
      surveillance. Little is known about Dukoral's long-term protective efficacy. Both
      of these vaccines have questionable compositions, using V. cholerae O1 strains
      isolated in 1947 that have been inactivated by heat and formalin treatments that
      may denature protein. Immunological studies revealed Dukoral's reduced and short
      lived efficacy, as measured by several immunological endpoints. Various factors,
      such as the necessity for multiple doses, poor protection of children under 5
      years of age, the requirement of a cold supply chain, production costs, and
      complex logistics of vaccine delivery, greatly reduce the suitability of either
      of these vaccines for endemic or epidemic cholera control in resource-poor
      settings.

PMID- 25056362
TI  - A novel live vector group A streptococcal emm type 9 vaccine delivered
      intranasally protects mice against challenge infection with emm type 9 group A
      streptococci.
AB  - The availability of a protective vaccine against Streptococcus pyogenes (group A
      Streptococcus [GAS]) is a priority for public health worldwide. Here, we have
      generated six live vaccine strains, each engineered to express an N-terminal M
      protein peptide from one of six of the most prevalent emm types of GAS (M1, M2,
      M4, M9, M12, and M28). The vaccine strains are based on a food-grade Lactococcus
      lactis strain and do not bear any antibiotic resistance. Mice immunized with the
      vaccine strain expressing the M9 peptide (termed here the L. lactis M9 strain)
      showed high titers of serum antibodies when delivered intranasally. Mice
      immunized with the L. lactis M9 strain were protected against infection after
      intranasal challenge with type 9 streptococci. Several parameters of disease,
      such as weight loss, body temperature, colony counts in mouth washes, and lung
      histology, were significantly improved in immunized mice compared to naive
      control mice. Our results indicate that intranasal delivery of the L. lactis M9
      strain live bacterial vaccine induced GAS-specific IgG titers, prevented
      pharyngeal colonization of GAS, and protected mice from disease upon challenge.
      The design of this vaccine prototype may provide a lower cost alternative to
      vaccines comprised of purified recombinant proteins. 

PMID- 25056363
TI  - Hepatitis B virus antibody levels 7 to 9 years after booster vaccination in
      Alaska native persons.
AB  - Hepatitis B antibody persistence was assessed in individuals who had previously
      received a vaccine booster. We measured hepatitis B surface antigen antibody
      (anti-HBs) levels 7 to 9 years post-hepatitis B booster in individuals with
      primary vaccination at birth. While 95 (91.3%) of 104 participants had detectable
      anti-HBs (minimum, 0.1 mIU/ml; maximum, 1,029 mIU/ml), only 43 (41%) had
      protective levels of >=10 mIU/ml. Pre- and week 4 postbooster anti-HBs levels
      were significant predictors of hepatitis B immunity at follow-up (P < 0.001).
      Almost all participants had detectable anti-HBs 7 to 9 years after the hepatitis
      B vaccine booster, but less than half had levels >=10 mIU/ml.

PMID- 25056364
TI  - A new modified live porcine reproductive and respiratory syndrome vaccine
      improves growth performance in pigs under field conditions.
AB  - The change in growth performance resulting from a new modified live porcine
      reproductive and respiratory syndrome (PRRS) vaccine was evaluated under field
      conditions for registration with the government as guided by the Republic of
      Korea's Animal and Plant Quarantine Agency. Three farms were selected based on
      their history of PRRS-associated respiratory diseases. On each farm, a total of
      45 3-week-old pigs were randomly allocated to one of two treatment groups, (i)
      vaccinated (n = 25) or (ii) control (n = 20) animals. A new modified live PRRSV
      vaccine increased market weight by 1.26 kg/pig (104.71 kg versus 103.45 kg; P <
      0.05) and decreased mortality by 17% (1.33% versus 18.33%; P < 0.05).
      Pathological examination indicated that vaccination effectively reduced
      microscopic lung lesions compared with control animals on the 3 farms. Thus, the
      new modified live PRRS vaccine improved growth performance and decreased
      mortality and lung lesions when evaluated under field conditions. 

PMID- 25056365
TI  - A pulse radiolysis study of the dynamics of ascorbic acid free radicals within a
      liposomal environment.
AB  - The dynamics of free-radical species in a model cellular system are examined by
      measuring the formation and decay of ascorbate radicals within a liposome with
      pulse radiolysis techniques. Upon pulse radiolysis of an N2O-saturated aqueous
      solution containing ascorbate-loaded liposome vesicles, ascorbate radicals are
      formed by the reaction of OH(.) radicals with ascorbate in unilamellar vesicles
      exclusively, irrespective of the presence of vesicle lipids. The radicals are
      found to decay rapidly compared with the decay kinetics in an aqueous solution.
      The distinct radical reaction kinetics in the vesicles and in bulk solution are
      characterized, and the kinetic data are analyzed.

PMID- 25056366
TI  - Studies on growth kinetics of Serratia marcescens VITSD2 and optimization of
      fermentation conditions for serratiopeptidase production.
AB  - Serratia is one of the most important groups of bacteria which produces
      proteolytic enzymes effectively and known to possess anti- inflammatory
      properties. The main focus of the current study was to optimize the culture
      conditions of Serratia marcescens VITSD2 for the mass production of
      serratiopeptidase. Effect of various nutritional and environmental factors were
      analysed and optimized. Among the different carbon and nitrogen sources tested,
      mannose and soya bean meal was found to be the best with enzyme activity of 1391
      units /mL and 1800 U/mL respectively. The enzyme showed an optimum activity of
      1668 U/mL at pH-8 and 1500 U/mL at 25oC. Maximum peptidase production during
      fermentation was obtained after 24 h incubation with 1% inoculum in the medium at
      25oC and yielded 1668 U/mL. Lysine stimulated the production of peptidase and the
      yield obtained was 2410U/mL. Growth curve analysis was done. Maximum
      serratiopeptidase production was detected after 24 h incubation with 2155
      units/mL and cell density of 2.4g/100mL. Hence the observation of the present
      study clearly indicates that the yield of Serratiopeptidase was found to be
      maximum by varying the cultural conditions.

PMID- 25056367
TI  - Extreme nursing: a qualitative assessment of nurse retention in a remote setting.
AB  - INTRODUCTION: Nurses have practiced in Bristol Bay, Alaska, since 1896. Practice
      opportunities are defined by institutional structures and systems; and the
      geography, climate, and history of remote South-west 'bush' Alaska. The Native
      Alaskan culture as experienced through nurses' practice, community relations, and
      in several cases, marriages, shapes their lives as well. The purposes of this
      qualitative study are three-fold: (1) to ensure the unique stories of bush Alaska
      nurses are preserved and told; (2) to foster a strong bush nursing tradition; and
      (3) to inform recruitment, hiring, and retention practices in remote settings.
      METHODS: Ten of 14 long-term retained (>15 years) nurses still living in Bristol
      Bay were interviewed using a semi-structured format, based on three broad
      interview questions: (1) Why did you come to Bristol Bay?; (2) If you ever wanted
      to leave, what motivated you to stay?; and (3) What do you feel are your greatest
      accomplishments here? Extensive probing and dialogue was employed to develop
      participants' conversation. Interviews were recorded, transcribed and coded for
      qualitative content analysis of ideas and thematic analysis. To preserve
      authenticity and enhance fidelity, nurses' verbatim statements are reported at
      length, illustrating ideas and themes. RESULTS: Analysis of transcripts revealed
      seven ideas common to all 10 long-term retained nurse's experience in the bush:
      family, culture, hardship, nursing practice, fish, motivations and community.
      Religion or spirituality was also a common idea, but not universal. A racism code
      was derived to illuminate less articulated ideas from the nurses' conversation.
      CONCLUSIONS: Long-term retained bush nurses share three characteristics useful to
      successful recruitment and retention efforts: they have (1) a strong sense of
      adventure, (2) an independent outlook regarding family growth and development,
      and (3) a deep appreciation of Native Alaskan culture and lifestyle. In summary
      they advise nurses who wish to practice and stay in the bush to come with 'ample
      resources, mental resources, emotional, spiritual, the whole nine yards, [they]
      need these resources in order to survive, in order to stay here. [Also] a love
      for the people, not being opposite to the culture but trying to learn [from it]'.
      Attributes and qualities nurses bring to remote South-west bush Alaska produce a
      community dynamic affecting practice, health, and quality of life.

PMID- 25056368
TI  - The efficacy and tolerability of cariprazine in acute mania associated with
      bipolar I disorder: a phase II trial.
AB  - OBJECTIVES: Cariprazine, an orally active and potent dopamine D3 and D2 receptor
      partial agonist with preferential binding to D3 receptors, is being developed for
      the treatment of schizophrenia and bipolar mania. This Phase II trial evaluated
      the efficacy, safety, and tolerability of cariprazine versus placebo in the
      treatment of acute manic or mixed episodes associated with bipolar I disorder.
      METHODS: This was a multinational, randomized, double-blind, placebo-controlled,
      flexible-dose study of cariprazine 3-12 mg/day in patients with acute manic or
      mixed episodes associated with bipolar I disorder. Following washout, patients
      received three weeks of double-blind treatment. The primary and secondary
      efficacy parameters were change from baseline to Week 3 in Young Mania Rating
      Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S) scores,
      respectively. Post-hoc analysis evaluated changes on YMRS single items. RESULTS:
      In each group, 118 patients received double-blind treatment; 61.9% of placebo and
      63.6% of cariprazine patients completed the study. The overall mean daily dose of
      cariprazine was 8.8 mg/day. At Week 3, cariprazine significantly reduced YMRS and
      CGI-S scores versus placebo, with least square mean differences of -6.1 (p <
      0.001) and -0.6 (p < 0.001), respectively. On each YMRS item, change from
      baseline to Week 3 was significantly greater for cariprazine versus placebo (all,
      p < 0.05). A significantly greater percentage of cariprazine patients than
      placebo patients met YMRS response (48% versus 25%; p < 0.001) and remission (42%
      versus 23%; p = 0.002) criteria at Week 3. Adverse events (AEs) led to
      discontinuation of 12 (10%) placebo and 17 (14%) cariprazine patients. The most
      common AEs (> 10% for cariprazine) were extrapyramidal disorder, headache,
      akathisia, constipation, nausea, and dyspepsia. Changes in metabolic parameters
      were similar between groups, with the exception of fasting glucose; increases in
      glucose were significantly greater for cariprazine versus placebo (p < 0.05).
      Based on Barnes Akathisia Rating Scale and Simpson-Angus Scale scores, more
      cariprazine than placebo patients experienced treatment-emergent akathisia
      (cariprazine: 22%; placebo: 6%) or extrapyramidal symptoms (parkinsonism)
      (cariprazine: 16%; placebo: 1%). CONCLUSION: Cariprazine demonstrated superior
      efficacy versus placebo and was generally well tolerated in patients experiencing
      acute manic or mixed episodes associated with bipolar I disorder.

PMID- 25056369
TI  - Platelet function inhibitors and platelet function testing in neurointerventional
      procedures.

PMID- 25056373
TI  - Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor
      1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer.
AB  - PURPOSE: We performed a phase I trial to investigate the safety, clinical
      responses, and Wilms' tumor 1 (WT1)-specific immune responses following treatment
      with dendritic cells (DC) pulsed with a mixture of three types of WT1 peptides,
      including both MHC class I and II-restricted epitopes, in combination with
      chemotherapy. EXPERIMENTAL DESIGN: Ten stage IV patients with pancreatic ductal
      adenocarcinoma (PDA) and 1 patient with intrahepatic cholangiocarcinoma (ICC) who
      were HLA-positive for A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03,
      DRB1*15:01, DRB1*15:02, DPB1*05:01, or DPB1*09:01 were enrolled. The patients
      received one course of gemcitabine followed by biweekly intradermal vaccinations
      with mature DCs pulsed with MHC class I (DC/WT1-I; 2 PDA and 1 ICC), II (DC/WT1
      II; 1 PDA), or I/II-restricted WT1 peptides (DC/WT1-I/II; 7 PDA), and
      gemcitabine. RESULTS: The combination therapy was well tolerated. WT1-specific
      IFNgamma-producing CD4(+) T cells were significantly increased following
      treatment with DC/WT1-I/II. WT1 peptide-specific delayed-type hypersensitivity
      (DTH) was detected in 4 of the 7 patients with PDA vaccinated with DC/WT1-I/II
      and in 0 of the 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II. The
      WT1-specific DTH-positive patients showed significantly improved overall survival
      (OS) and progression-free survival (PFS) compared with the negative control
      patients. In particular, all 3 patients with PDA with strong DTH reactions had a
      median OS of 717 days. CONCLUSIONS: The activation of WT1-specific immune
      responses by DC/WT1-I/II combined with chemotherapy may be associated with
      disease stability in advanced pancreatic cancer.

PMID- 25056377
TI  - Chyle leak following biliary pancreatitis.
AB  - Chylous ascites is a rare clinical entity that historically has been accompanied
      by high mortality due to the association with malignancy. Here we present a case
      of chylous ascites as a complication of mild pancreatitis in a young woman. We
      review the literature of similar cases, which revealed four similar cases with a
      range of outcomes. Treatment options vary from dietary restriction of medium
      chain fatty acids, total parental nutrition, radiological intervention and
      surgery. 

PMID- 25056374
TI  - Integrative and comparative genomic analysis of HPV-positive and HPV-negative
      head and neck squamous cell carcinomas.
AB  - PURPOSE: The genetic differences between human papilloma virus (HPV)-positive and
      -negative head and neck squamous cell carcinomas (HNSCC) remain largely unknown.
      To identify differential biology and novel therapeutic targets for both entities,
      we determined mutations and copy-number aberrations in a large cohort of
      locoregionally advanced HNSCC. EXPERIMENTAL DESIGN: We performed massively
      parallel sequencing of 617 cancer-associated genes in 120 matched tumor/normal
      samples (42.5% HPV-positive). Mutations and copy-number aberrations were
      determined and results validated with a secondary method. RESULTS: The overall
      mutational burden in HPV-negative and HPV-positive HNSCC was similar with an
      average of 15.2 versus 14.4 somatic exonic mutations in the targeted cancer
      associated genes. HPV-negative tumors showed a mutational spectrum concordant
      with published lung squamous cell carcinoma analyses with enrichment for
      mutations in TP53, CDKN2A, MLL2, CUL3, NSD1, PIK3CA, and NOTCH genes. HPV
      positive tumors showed unique mutations in DDX3X, FGFR2/3 and aberrations in
      PIK3CA, KRAS, MLL2/3, and NOTCH1 were enriched in HPV-positive tumors. Currently
      targetable genomic alterations were identified in FGFR1, DDR2, EGFR, FGFR2/3,
      EPHA2, and PIK3CA. EGFR, CCND1, and FGFR1 amplifications occurred in HPV-negative
      tumors, whereas 17.6% of HPV-positive tumors harbored mutations in fibroblast
      growth factor receptor genes (FGFR2/3), including six recurrent FGFR3 S249C
      mutations. HPV-positive tumors showed a 5.8% incidence of KRAS mutations, and DNA
      repair gene aberrations, including 7.8% BRCA1/2 mutations, were identified.
      CONCLUSIONS: The mutational makeup of HPV-positive and HPV-negative HNSCC differs
      significantly, including targetable genes. HNSCC harbors multiple therapeutically
      important genetic aberrations, including frequent aberrations in the FGFR and
      PI3K pathway genes. See related commentary by Krigsfeld and Chung, p. 495.

PMID- 25056376
TI  - Pre-flight assessment in patients with obesity hypoventilation syndrome.
AB  - BACKGROUND AND OBJECTIVE: Reduced atmospheric pressure during air travel can
      cause significant hypoxaemia in some patients with respiratory disease. Our aims
      were to investigate the degree of hypoxaemia in patients with obesity
      hypoventilation syndrome (OHS) during hypoxic challenge test (HCT), and to
      identify any predictors of a positive HCT. METHODS: Thirteen patients underwent
      assessment, including HCT, lung function and incremental shuttle walk test. All
      had OHS well controlled with long-term nocturnal non-invasive ventilation (NIV).
      Patients with chronic obstructive pulmonary disease were excluded. A positive HCT
      was defined according to the British Thoracic Society (BTS) recommendation as
      arterial oxygen tension (PaO2) <6.6 kPa and/or oxygen saturation <85%. RESULTS:
      Mean age was 57 (+/- 11) years. Mean body mass index was 51.7 (+/- 12) kg/m(2) .
      Mean baseline PaO2 and arterial carbon dioxide tension (PaCO2) were 10.2 (9.5
      11.3) kPa and 5.2 (3.7-6.8) kPa, respectively. Seven patients (54%) had a
      positive HCT. The correlation between baseline PaO2 and PaO2 at the end of the
      HCT was not statistically significant (r = 0.433, P = 0.184). A negative
      correlation was observed between baseline PaCO2 and PaO2 at the end of the HCT (r
      = -0.793, P = 0.004). A positive correlation was observed between the distance
      walked and the PaO2 at the end of the HCT (r = 0.608, P = 0.047). CONCLUSIONS:
      OHS is a risk factor for severe hypoxaemia during air travel even if the
      ventilatory failure is well controlled. An HCT before air travel is advisable in
      all OHS patients. Those with positive HCT may use NIV or have oxygen on-board as
      per BTS recommendation.

PMID- 25056375
TI  - Evidence for molecular differences in prostate cancer between African American
      and Caucasian men.
AB  - PURPOSE: The aim of this study was to compare the frequency of ERG rearrangement,
      PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in
      African American and Caucasian men. EXPERIMENTAL DESIGN: Dominant tumor nodules
      from radical prostatectomy specimens of 105 African American men (AAM) were
      compared with 113 dominant nodules from Caucasian men (CaM). Clinical and
      pathologic characteristics of the two groups were similar. SPINK1 overexpression
      was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by
      FISH, and SPOP mutation by Sanger sequencing. RESULTS: ERG rearrangement was
      identified in 48 of 113 tumors (42.5%) in CaM and 29 of 105 tumors (27.6%) in AAM
      (P = 0.024). PTEN deletion was seen in 19 of 96 tumors (19.8%) in CaM and 7 of
      101 tumors (6.9%) in AAM (P = 0.011). SPINK1 overexpression was present in 9 of
      110 tumors (8.2%) in CaM and 25 of 105 tumors (23.4%) in AAM (P = 0.002). SPOP
      mutation was identified in 8 of 78 (10.3%) tumors in CaM and 4 of 88 (4.5%)
      tumors in AAM (P = 0.230). When adjusted for age, body mass index, Gleason score,
      and pathologic stage, ERG rearrangement and SPINK1 overexpression remain
      significantly different (P = 0.018 and P = 0.008, respectively), and differences
      in PTEN deletion and SPOP mutation approach significance (P = 0.061 and P =
      0.087, respectively). CONCLUSIONS: Significant molecular differences exist
      between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration
      associated with more aggressive prostate cancers, was more frequent in AAM,
      whereas ERG rearrangement and PTEN deletion were less frequent in this cohort.
      Further investigation is warranted to determine whether these molecular
      differences explain some of the disparity in incidence and mortality between
      these two ethnic groups.

PMID- 25056378
TI  - Pancreatic paraganglioma - a rare and dangerous entity. Vascular anatomy and
      impact on management.
AB  - Pancreatic paragangliomas are extremely rare with less than 20 cases ever
      described in the world literature. There is no detailed report of the vascular
      anatomy in this entity and its possible impact on patient management. We present
      a case of large pancreatic head paraganlioma in a 53-year-old woman. The tumour
      had a predominant arterial blood supply via both the hepatic artery and the
      superior mesenteric artery. Complex inflow was complemented by supplementary
      branches from the right renal artery. The arteriovenous communications within the
      lesion represented the most dangerous aspect of excision and the tumour removal
      was accompanied with a considerable blood loss. After pancreaticoduodenectomy,
      patient experienced transient elevation of liver function tests with no other
      identifiable cause than a change in portal haemodynamics. It is advisable that
      the precise knowledge of vascular anatomy in pancreatic head paraganglioma should
      be obtained prior to any intervention. 

PMID- 25056379
TI  - User-centered design of a web-based self-management site for individuals with
      type 2 diabetes - providing a sense of control and community.
AB  - BACKGROUND: To design and test a web-based self-management tool for patients with
      type 2 diabetes for its usability and feasibility. METHODS: An evidence-based,
      theory-driven website was created for patients with type 2 diabetes. Twenty-three
      patients with type 2 diabetes aged >= 25 years were recruited from 2 diabetes
      care centers in Toronto, Canada. We employed focus group methodology to assess
      acceptability, sustainability, strengths and weaknesses of the self-management
      website. Based on these results, revisions were made to the website. Three cycles
      of individual usability testing sessions using cognitive task analysis were
      conducted with patients with type 2 diabetes. Revisions to the website were made
      based on results from this testing. RESULTS: We identified five themes concerning
      participants' experiences of health care and related unmet needs: 1) Desire for
      information and for greater access to timely and personalized care to gain a
      sense of control of their disease; 2) Desire for community (sharing experiences
      with others) to fulfill practical and emotional needs; 3) Potential roles of an
      online self-management website in self-empowerment, behavior change, self
      management and health care delivery; 4) Importance of a patient-centered
      perspective in presenting content (e.g. common assumptions, medical nomenclature,
      language, messaging, sociocultural context); 5) Barriers and facilitators to use
      of a self-management website (including perceived relevance of content,
      incorporation into usual routine, availability for goal-directed use, usability
      issues). CONCLUSIONS: Participants outlined a series of unmet health care needs,
      and stated that they wanted timely access to tailored knowledge about their
      condition, mechanisms to control and track their disease, and opportunities to
      share experiences with other patients. These findings have implications for
      patients with type 2 diabetes of diverse ages, socioeconomic backgrounds, and
      disease severity, as well as to the design of other computer-based resources for
      chronic disease management.

PMID- 25056380
TI  - GPs should not be solely responsible for assessing entitlement to benefits, MPs
      say.

PMID- 25056381
TI  - The efficacy and tolerability of frovatriptan and dexketoprofen for the treatment
      of acute migraine attacks.
AB  - Frovatriptan is a triptan characterized by a high affinity for 5-HT1B/1D
      receptors and a long half-life contributing to a more sustained and prolonged
      action than other triptans. Dexketoprofen is a nonsteroidal anti-inflammatory
      drug with a relatively short half-life and rapid onset of action, blocking the
      action of cyclo-oxygenase, which is involved in prostaglandins' production, thus
      reducing inflammation and pain. Both drugs have been successfully employed as
      monotherapies for the treatment of acute migraine attacks. The combination of
      these two drugs (frovatriptan 2.5 mg plus dexketoprofen 25 or 37.5 mg) has been
      tested in migraine sufferers, showing a rapid and good initial efficacy, with 2-h
      pain free rates of 51%, and a high persistence in the 48-h following the onset of
      pain: recurrence occurred in only 29% of attacks and sustained pain free rates
      were 43% at 24- and 33% at 48-h. 

PMID- 25056382
TI  - Management of anxiety and motor symptoms in Parkinson's disease.
AB  - Parkinson's disease (PD) is typically known for its cardinal motor symptoms, but
      a growing body of literature is recognizing a multitude of important nonmotor
      symptoms as well. Anxiety is one of the most common nonmotor symptoms of PD;
      unfortunately, neither the management of anxiety nor its influence on motor
      symptoms is well understood. While recent literature indicates a correlation
      between motor symptoms and anxiety in PD, it remains uncertain whether one
      symptom acts as the underlying cause of the other. This review considers the
      cyclic interaction between anxiety and motor symptoms in PD, each exacerbating
      the other when they coexist. It may be critically important to disentangle if one
      symptom serves as an underlying cause of the other, since this might dictate
      appropriate treatment. Neuroanatomical substrates as well as the treatments for
      both motor symptoms and anxiety are discussed in detail to consider the evidence
      base for the management of PD. 

PMID- 25056383
TI  - Reproducibility of computed tomography to evaluate ankle and hindfoot fusions.
AB  - BACKGROUND: Although plain radiographs have been historically used to evaluate
      the status of arthrodesis in the foot and ankle, computed tomography (CT) has
      gained popularity for evaluation of fusion status. The degree of fusion
      identified on CT scan has been correlated with functional outcome, with an
      arthrodesis area of 25-50% necessary for clinical success. In the clinical
      setting, orthopaedic surgeons often evaluate CT scans independently. The purpose
      of this study was to evaluate the interrater reliability of CT scans to assess
      the status of hindfoot or ankle fusions among orthopaedic foot and ankle
      surgeons. METHODS: Forty-one CT scans were identified retrospectively from the
      tertiary referral practices of 4 fellowship-trained orthopaedic foot and ankle
      surgeons. Inclusion criteria were patients with ankle, subtalar, or
      tibiotalocalcaneal fusions. Fusions with bulk allograft were excluded. All CT
      scans were completed at the investigating institution. The primary author (RAC)
      reviewed all CT scans to ensure the adequacy and completeness of the films.
      Images were blinded of any patient identifiers. All 4 surgeons individually
      reviewed the blinded scans and determined whether the arthrodesis site was
      greater than or less than 50% fused. Interrater reliability was completed via
      kappa analysis. RESULTS: Based on kappa analysis, there was high interrater
      reliability in the assessment of subtalar arthrodesis. This was not statistically
      significant for the evaluation of ankle arthrodesis. CONCLUSION: The CT scan has
      become instrumental in determining the adequacy of arthrodesis in the foot and
      ankle. The present study demonstrates the reliability of orthopaedic surgeons to
      ascertain the status of subtalar arthrodesis via CT scan. LEVEL OF EVIDENCE:
      Level IV, case series.

PMID- 25056384
TI  - Correction of moderate to severe hallux valgus with isometric first metatarsal
      double osteotomy.
AB  - BACKGROUND: The operative treatment for the moderate to severe bunion continues
      to present challenges. The indications for a single, double, or triple first ray
      osteotomy remain controversial. In addition, it is not clear whether an opening
      wedge osteotomy leads to clinically relevant arthritis at the first
      metatarsophalangeal joint. However, it is this theoretical concern that has led
      the authors to develop an isometric correction of the first ray. METHODS: Thirty
      two patients underwent operative correction of hallux valgus with a double
      osteotomy of the first metatarsal using an opening wedge proximally and a closing
      wedge distally. The mean follow-up period was 59.3 months with a range of 55 to
      65 months. RESULTS: The 1-2 intermetatarsal angle preoperatively was a mean of
      18.9 degrees (range 17-23), correcting postoperatively to a mean angle of 8.6
      degrees (range 5-12), for an average correction of 10.4 degrees (range 6-16). The
      postoperative AOFAS scores were 39.4 out of 40 points for pain, 42.4 out of 45
      points for function, and 15 points for alignment. The total score was excellent
      with 94.2 out of 100 possible points. Radiographic union occurred in all cases.
      There was one case of painful edema of the foot and two cases of early avascular
      necrosis (AVN) diagnosed by residual pain at the hallux metatarsophalangeal joint
      and transient osteopenia of the metatarsal head on radiographs. No late sequelae
      associated with AVN such as arthritis or metatarsal head collapse were noted with
      long-term follow-up. These healed within months without specific treatment.
      CONCLUSION: A double osteotomy of the first metatarsal with a nonlocking, low
      profile plate was an effective procedure for correcting severe hallux valgus that
      carried a low complication rate and high patient satisfaction. It has clear
      advantages over isolated opening wedge procedures, including potentially better
      correction especially in those bunions associated with an increased distal
      metatarsal articular angle. LEVEL OF EVIDENCE: Level IV, retrospective case
      series.

PMID- 25056386
TI  - Combining forces to combat infectious diseases.
AB  - Because the threat of infectious diseases can cause widespread fear in a
      community, these diseases receive much public attention. Collaborations that
      bring together industry, academia, regulators, and the public can lead to
      improved and accelerated drug development. The collaborations must be grounded in
      strong science and expertise in clinical trials. Development of drugs to treat
      infections caused by resistant bacteria, drugs to treat hepatitis C virus (HCV),
      and drugs to prevent HIV is taking advantage of these collaborations. 

PMID- 25056389
TI  - The use of model-based tumor-size metrics to predict survival.

PMID- 25056390
TI  - Assessment of tumor growth inhibition metrics to predict overall survival.

PMID- 25056391
TI  - CYP2D6 genotype and adjuvant tamoxifen.

PMID- 25056392
TI  - CYP2D6 genotype and tamoxifen: considerations for proper nonprospective studies.

PMID- 25056393
TI  - Interpreting the CYP2D6 results from the International Tamoxifen Pharmacogenetics
      Consortium.

PMID- 25056394
TI  - Antibacterial drug development: challenges, recent developments, and future
      considerations.
AB  - A decline in antibacterial drug development coupled with emerging bacterial
      resistance has resulted in limited treatment options. One of the challenges
      facing antibacterial drug development is appropriate clinical trial designs.
      Noninferiority trials are appropriate to study new antibacterial drugs for the
      treatment of serious diseases; superiority trials can be challenging and cannot
      be the only acceptable trial design to study antibacterial drugs. Our efforts
      must continue to make new therapies available to meet patient needs. 

PMID- 25056395
TI  - Use of internet search logs to evaluate potential drug adverse events.
AB  - Internet search logs provide an abundant source of data that can be explored for
      purposes such as identifying drug exposure-adverse event relationships. The
      methodology to rigorously conduct such evaluations is not well characterized, and
      the utility of such analyses is not well defined. In this issue, White and
      colleagues propose an approach using Internet search logs for this purpose and
      compare it to parallel analyses conducted using the US Food and Drug
      Administration's spontaneous reporting database. 

PMID- 25056396
TI  - Prioritized current unmet needs for antibacterial therapies.
AB  - As a result of declining new antibacterial approvals and rising antibiotic
      resistance, society clearly needs new treatments for bacterial infections.
      Specific areas of unmet need evolve over time owing to changes in resistance
      patterns and treatment strategies. Our goal here is to describe and prioritize
      the current areas of greatest unmet need for new antibacterial development based
      on an understanding of the most serious treatment challenges facing patients and
      their providers today. 

PMID- 25056397
TI  - Regulatory considerations for antiretroviral prophylaxis to prevent HIV
      acquisition.
AB  - Antiretrovirals (ARVs) decrease the infectiousness of treated HIV-infected
      persons and can reduce the acquisition of HIV infection when taken by uninfected
      persons. Coformulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is
      approved in the United States for the preexposure prophylaxis (PrEP) indication,
      changing the regulatory landscape for new prophylactic agents. We describe the
      challenge of conducting rigorous clinical end-point trials for prophylactic
      agents and point to alternatives that leverage new information about correlates
      of HIV risk and protection.

PMID- 25056398
TI  - Radiological studies on the best entry point and trajectory of anterior cervical
      pedicle screw in the lower cervical spine.
AB  - OBJECTIVE: To explore the best entry point and trajectory of anterior cervical
      transpedicular screws in the lower cervical spine by radiological studies, and
      provide reference for clinical application. METHODS: Fifty patients were scanned
      by computed tomography and confirmed no obvious defect of the cervical spine. On
      horizontal axis, camber angle (alpha) and axial length (AL) were measured from C3
      to C7. On sagittal view, the cranial or caudal angle (beta) and sagittal length
      (SL) were also measured from C3 to C7. On the sagittal and horizontal planes
      vertebrae were respectively divided into four areas, ordered 1-4, on the anterior
      side of the pedicle. The areas and angles of pedicle intersect into the vertebral
      body were recorded. We inserted six anterior pedicle screws into the lower
      cervical spine of three patients by this technique. RESULTS: On transverse plane,
      camber angle (alpha) of C3-C5 increased gradually, while it decreased from C5 to
      C7. On sagittal view, C3 and C4 pedicles showed cranial tilting, while C5 to C7
      were caudally tilted. AL and SL values increased gradually from C3 to C7. The
      number of the intersections of C3-C7 in each area was also different. Six pedicle
      screws of three cases were inserted into the lower cervical spine with proper
      placement and no complications. CONCLUSION: Anterior transpedicular screw (ATPS)
      is a theoretically feasible option for internal fixation. The technique described
      in this paper was subsequently used in three patients without complication.
      Future improvement of ATPS insertion remains necessary for this technically
      demanding procedure.

PMID- 25056399
TI  - Evolution of functional diversification within quasispecies.
AB  - According to quasispecies theory, high mutation rates limit the amount of
      information genomes can store (Eigen's Paradox), whereas genomes with higher
      degrees of neutrality may be selected even at the expenses of higher replication
      rates (the "survival of the flattest" effect). Introducing a complex genotype to
      phenotype map, such as RNA folding, epitomizes such effect because of the
      existence of neutral networks and their exploitation by evolution, affecting both
      population structure and genome composition. We reexamine these classical results
      in the light of an RNA-based system that can evolve its own ecology. Contrary to
      expectations, we find that quasispecies evolving at high mutation rates are steep
      and characterized by one master sequence. Importantly, the analysis of the system
      and the characterization of the evolved quasispecies reveal the emergence of
      functionalities as phenotypes of nonreplicating genotypes, whose presence is
      crucial for the overall viability and stability of the system. In other words,
      the master sequence codes for the information of the entire ecosystem, whereas
      the decoding happens, stochastically, through mutations. We show that this
      solution quickly outcompetes strategies based on genomes with a high degree of
      neutrality. In conclusion, individually coded but ecosystem-based diversity
      evolves and persists indefinitely close to the Information Threshold. 

PMID- 25056400
TI  - Large B-cell lymphoma mimicking iliopsoas abscess following open revision of
      proximal femur infected non-union: a case report.
AB  - BACKGROUND: Extranodal presentation of lymphoma is a rare occurrence. It has been
      postulated that chronic antigen stimulation may predispose a patient to the
      development of lymphoma. CASE PRESENTATION: We present a case report of a large
      extranodal B-cell lymphoma mimicking a postoperative abscess following surgery
      for an infected proximal femur nonunion in an 80-year-old Caucasian male of
      Italian descent. CONCLUSIONS: This case highlights the need to consider
      malignancy in revision surgery, careful examination of operative specimens and
      the need for further understanding of the role of metal implants in chronic
      antigen stimulation.

PMID- 25056401
TI  - Obesity and sleepiness in women with fibromyalgia.
AB  - Fibromyalgia (FM) is associated with a number of comorbidities, including chronic
      widespread pain, fatigue and non-restorative sleep. Evidence has shown that FM is
      closely associated with overweight and obesity. The objective of the present
      study was to investigate the relationship between obesity and sleepiness in women
      with FM. A total of 100 adult female patients with a prior medical diagnosis of
      FM participated in the study. Body mass, height and waist circumference were
      measured, and body mass index (BMI) was calculated. The diet quality was
      evaluated by the Healthy Eating Index. Subjective analyses of daytime sleepiness
      [Epworth Sleepiness Scale (ESS)] and sleep quality (Pittsburgh Sleep Quality)
      were performed. An obesity rate of 41 % was found in all women (56.1 % were
      sleepy and 43.9 % were not, p = 0.04). Obese women showed a greater level of
      sleepiness when compared with non-obese (10.2 and 7.0, respectively, p = 0.004).
      Sleepy women showed a greater weight gain after the diagnosis of FM when compared
      with non-sleepy women (11.7 and 6.4 kg, respectively, p = 0.04). A positive and
      significant correlation between BMI and sleepiness (r = 0.35, p = 0.02) was also
      found. In multivariate logistic regression, moderate or severe sleepiness (ESS
      >12) was associated with obesity (odds ratio 3.44, 95 % CI 1.31-9.01, p = 0.04).
      These results demonstrate an important association between sleepiness and FM,
      suggesting that the occurrence of obesity may be involved with sleepiness in
      these patients.

PMID- 25056402
TI  - Frequent involvement of central nervous system in primary Sjogren syndrome.
AB  - Primary Sjogren syndrome (pSS) is a systemic autoimmune disease characterized by
      lymphocytic infiltration of the salivary and tear glands, and autoantibody
      secretion, in the absence of other systemic autoimmune disorder. Among autoimmune
      diseases, it is a relatively common disease, but the burden of central nervous
      system (CNS) involvement is controversial. This retrospective study evaluates the
      prevalence, clinical patterns and outcomes of CNS involvement in a cohort of
      patients with primary Sjogren syndrome. We evaluated 93 patients with pSS
      diagnosed according to American-European Consensus Group criteria. Fourteen
      patients (15.1 %) had CNS involvement. All were women with an average age of
      onset of the disease of 42.1 +/- 14.7 years (average +/- SD) and an average age
      of onset of neurological involvement of 47.29 +/- 16 years. Three had
      parkinsonian syndrome, two epilepsy, two motor and sensory deficits, two headache
      with brain magnetic resonance abnormalities, two neuromyelitis optica, two
      chronic progressive myelitis and one aseptic meningitis. Neurological involvement
      preceded Sjogren syndrome diagnosis in nine of the patients (64 %), and
      neurological outcome was good in 11 patients (78.6 %). Central nervous
      involvement was not as rare as expected, and the frequency was similar to the
      frequency of peripheral nervous system involvement. In half of the patients, this
      was the first symptom of the disease, emphasizing the importance of considering
      this diagnosis, especially in young female with neurological symptoms without
      other evident cause.

PMID- 25056403
TI  - Vectorial diffusion for facile solution-processed self-assembly of insoluble
      semiconductors: a case study on metal phthalocyanines.
AB  - Solution processibility is one of the most intriguing properties of organic
      semiconductors. However, it is difficult to find a suitable solvent and solution
      process for most semiconductors. For example, metal phthalocyanines (MPcs) are
      only soluble in non-volatile solvents, which prevent their applications from
      solution process. For the first time, vectorial diffusion is utilized for
      solution processing of MPcs. The obtained large F16CuPc and alpha-phase CuPc
      crystals and the efficient phase separation of them suggest the vectorial
      diffusion process is as slow as a self-assembly process, which is helpful to
      yield large crystals and purify the semiconductors. This method, which only uses
      common commercial solvents without any complex and expensive instruments and high
      temperature operation, provides a facile approach for purification of organic
      semiconductors and growth of their crystals in large quantities.

PMID- 25056404
TI  - Cardiovascular disorders in anorexia nervosa and potential therapeutic targets.
AB  - Anorexia nervosa (AN) is an eating disorder in which a distorted self-perception
      of body image and an excessive fear of gaining weight result in extreme
      restrictions in eating habits. AN may be divided into two types: a "binge
      eating/purging type" during which the individual regularly engages in overeating
      and then purging behavior, and a "restricting type", in which she does not. AN is
      a serious medical problem in young people in Western societies. It is widely
      reported that patients with AN exhibit an enhanced mortality rate as compared
      with age-matched healthy subjects, which has been mainly ascribed to cardiac
      complications. At least one-third of all deaths in patients with anorexia nervosa
      are estimated to be due to cardiac causes, mainly sudden death. Cardiovascular
      complications of AN can be present in up to 80% of cases, and among them
      alterations in cardiac electrical activity, structure and hemodynamics have been
      reported as causes of morbidity and mortality. The objective of this brief review
      is to summarize current knowledge on the main cardiovascular complications of AN,
      their underlying mechanisms and the possible therapeutic approaches.

PMID- 25056405
TI  - Vitamin D: the more we know, the less we know.

PMID- 25056407
TI  - Editorial: Novel approaches to an old problem: insights, theory and practice for
      eliminating aging.

PMID- 25056406
TI  - General mechanism of two-state protein folding kinetics.
AB  - We describe here a general model of the kinetic mechanism of protein folding. In
      the Foldon Funnel Model, proteins fold in units of secondary structures, which
      form sequentially along the folding pathway, stabilized by tertiary interactions.
      The model predicts that the free energy landscape has a volcano shape, rather
      than a simple funnel, that folding is two-state (single-exponential) when
      secondary structures are intrinsically unstable, and that each structure along
      the folding path is a transition state for the previous structure. It shows how
      sequential pathways are consistent with multiple stochastic routes on funnel
      landscapes, and it gives good agreement with the 9 order of magnitude dependence
      of folding rates on protein size for a set of 93 proteins, at the same time it is
      consistent with the near independence of folding equilibrium constant on size.
      This model gives estimates of folding rates of proteomes, leading to a median
      folding time in Escherichia coli of about 5 s. 

PMID- 25056408
TI  - HSCIC outlines planned changes for making patient data more secure.

PMID- 25056409
TI  - Structure and electrical resistivity of mixed-valent EuNi2P2 at high pressure.
AB  - The structural properties and electrical resistivity of homogeneous mixed-valent
      EuNi2P2 are studied at pressures up to 45 GPa. No structural phase transition is
      observed in the whole pressure range and the overall pressure behavior of the
      structural parameters is similar to that of related compounds in the collapsed
      tetragonal ThCr2Si2-type structure. Electrical resistivity measured up to 31 GPa
      at temperatures between 4 and 300 K exhibits continuous changes from the behavior
      typical for a mixed-valent Eu system to that of a normal metallic system at
      pressures above 20 GPa, indicating a transition of the strongly mixed-valent Eu
      atoms with a valence ~2.5 towards a pure trivalent state. No superconductivity
      was observed in the whole studied pressure-temperature range.

PMID- 25056410
TI  - [Improvement of emergency physician education through simulator training.
      Consideration on the basis of the model project "NASimSaar25"].
AB  - BACKGROUND: Prehospital emergency medicine is a challenge for trainee emergency
      physicians. Rare injuries and diseases as well as patients in extreme age groups
      can unexpectedly face emergency physicians. In the regulations on medical
      education the German Medical Association requires participation in 50 emergency
      missions under the supervision of an experienced emergency physician. This needs
      to be improved because on-the-job training does not generally represent the whole
      spectrum of emergency medicine and a good and structured training under on call
      conditions is nearly impossible. AIM: The subject of the model project described
      was whether practical training for emergency physicians can be achieved by
      participation in simulation training instead of real emergency situations.
      MATERIAL AND METHODS: After modification of the Saarland regulations on medical
      education it was possible to replace up to 25 participations in emergency
      missions by simulation training. The concept of the course NASimSaar25 requires
      participants to complete 25 simulator cases in 3 days in small training groups.
      Emergency situations from all medical disciplines need to be treated. A special
      focus is on the treatment of life-threatening and rare diseases and injuries.
      Modern simulators and actors are used. The debriefings are conducted by
      experienced tutors based on approved principles. Medical contents, learning
      targets from the field of crew resource management (CRM) and soft skills are
      discussed in these debriefings. RESULTS: Education in the field of emergency
      medicine can be improved by simulator-based learning and training. However,
      practical work under a tutor in real and clinical experience cannot be completely
      replaced by simulation. Simulator training can only be successful if theoretical
      knowledge has already been acquired. CONCLUSION: A simulator-based course concept
      can result in an improvement of emergency medical education. The model project
      NASimSaar25 was well received by the target audience and mostly very well
      evaluated in terms of learning and reality. If this project becomes established
      the demand on simulation-based training will increase. The training should
      achieve a consistent standard of quality.

PMID- 25056411
TI  - [Risk consideration for peridural catheter removal in acute coronary syndrome.
      Epidural hematoma versus stent thrombosis].
AB  - Perioperative pain therapy using an epidural catheter is the standard operating
      procedure for numerous surgical interventions. The necessity of initiating
      anticoagulant therapy in a patient with an epidural catheter requires a careful
      weighing up between thromboembolic complications and epidural hematoma. The case
      presented here of a 47-year-old female patient who was operated on for mastectomy
      with a latissimus dorsi myocutaneous flap demonstrates a possible solution to
      this dilemma. The patient sustained a perioperative ST elevation myocardial
      infarction treated with drug-eluting stents while undergoing epidural pain
      therapy. By using the short-acting antiplatelet drug tirofiban over a time period
      of 7 days the gap for dual antiplatelet therapy was reduced with the help of
      specific platelet aggregation assays to a time frame of a few hours to minimize
      the risk of stent thrombosis. The epidural catheter was removed without
      complications under consideration of the current recommendations for regional
      anesthesia and antithrombotic agents. 

PMID- 25056412
TI  - Unification of the family of Garrison-Wright's phases.
AB  - Inspired by Garrison and Wight's seminal work on complex-valued geometric phases,
      we generalize the concept of Pancharatnam's "in-phase" in interferometry and
      further develop a theoretical framework for unification of the abelian geometric
      phases for a biorthogonal quantum system modeled by a parameterized or time
      dependent nonhermitian hamiltonian with a finite and nondegenerate instantaneous
      spectrum, that is, the family of Garrison-Wright's phases, which will no longer
      be confined in the adiabatic and nonadiabatic cyclic cases. Besides, we employ a
      typical example, Bethe-Lamb model, to illustrate how to apply our theory to
      obtain an explicit result for the Garrison-Wright's noncyclic geometric phase,
      and also to present its potential applications in quantum computation and
      information. 

PMID- 25056413
TI  - Effect of repeated adjunctive antimicrobial photodynamic therapy on subgingival
      periodontal pathogens in the treatment of chronic periodontitis.
AB  - The aim of this study was to compare the effect of subgingival ultrasonic scaling
      followed by repeated (three times) antimicrobial photodynamic therapy (PDT),
      ultrasonic scaling alone (US), and scaling and root planing with hand instruments
      (SRP) for initial periodontal treatment. Twenty-seven non-smoking systemically
      healthy chronic periodontitis patients were included. Residual pockets >=4 mm
      deep and bleeding on probing were debrided either with SRP, US alone, or US
      followed by a single episode of PDT during supportive periodontal treatment.
      Probing pocket depth (PPD), bleeding on probing (BOP), and clinical attachment
      level (CAL) were monitored over 12 months. The presence of five periodontal
      pathogens in the pockets was determined by a commercially available micro-IDent
      test. Intergroup and intragroup statistical analysis was performed. All three
      treatments resulted in a significant clinical improvement. Additional application
      of PDT to US failed to result in further improvement in terms of PPD reduction
      and CAL gain. However, it resulted in a higher reduction of BOP at 3 and 12
      months comparing to US alone or SRP (PDT from 25 to 13 and to 9%, US from 23 to
      16 and to 12%, and SRP from 17 to 10 and to 9%, respectively). PDT reduced the
      proportion of positive sites after 6 months for Treponema denticola (TD)
      significantly more effectively than US or SRP (p < 0.0001). Additionally, PDT
      resulted in a greater reduction of Aggregatibacter actinomycetemcomitans (AA),
      Tannerella forsythia (TF), and TD in medium pockets (4-6 mm) (p < 0.02) and of TD
      in deep pockets (>6 mm) compared to mechanical debridement alone (p < 0.05).

PMID- 25056414
TI  - Physiotherapists' Beliefs About Whiplash-associated Disorder: A Comparison
      Between Singapore and Queensland, Australia.
AB  - BACKGROUND AND PURPOSE: Healthcare providers' beliefs may play a role in the
      outcome of whiplash-associated disorders (WAD), a condition which is proposed to
      be culturally dependent. Clinical practice guidelines recommend an active
      approach for the management of WAD, which is often delivered by physiotherapists.
      However, there is no data on physiotherapists' whiplash beliefs. Our primary
      objective was to determine physiotherapists' beliefs from Queensland (Australia)
      and Singapore, two cultures with differing prevalence of chronic musculoskeletal
      pain and chronic WAD. METHODS: A pen and paper survey of musculoskeletal
      physiotherapists practicing in Queensland and Singapore was conducted.
      Participants completed questionnaires consisting of patient vignettes and
      statements inquiring knowledge and attitudes towards WAD. Chi-square tests of
      significance were used to compare the responses of physiotherapists from both
      samples. RESULTS: Ninety-one (response rate 45%) Queensland-based and 94
      (response rate 98%) Singapore-based physiotherapists participated in the study.
      The beliefs in the management strategies for the patient vignettes were generally
      consistent with practice guidelines. A higher proportion of Queensland-based
      physiotherapists expected permanent disabilities for the patient vignette
      depicting chronic WAD (Queensland: 55% Singapore: 28% Pearson chi-sq 18.76, p <
      0.005).Up to 99% of the physiotherapists from both samples believed in
      encouragement of physical activity, the effectiveness of exercise and multimodal
      physiotherapy for WAD. Significantly higher proportions of Singapore-based
      physiotherapists believed in ordering radiographs for acute WAD (Pearson chi-sq
      41.98, p < 0.001) and also believed in a psychogenic origin of chronic WAD
      (Pearson chi-sq 22.57, p  0.001). CONCLUSION: The majority of beliefs between
      physiotherapists in Queensland and Singapore were similar but there were specific
      differences. Physiotherapists' whiplash beliefs in Queensland and Singapore did
      not clearly reflect the difference in prevalence of chronic musculoskeletal pain
      or chronic WAD in Queensland and Singapore.

PMID- 25056415
TI  - E-vita open plus for treating complex aneurysms and dissections of the thoracic
      aorta: a NICE medical technology guidance.
AB  - The E-vita open plus is a one-stage endoluminal stent graft system used for
      treating complex aneurysms and dissections of the thoracic aorta. The National
      Institute for Health and Care Excellence (NICE), as a part of its Medical
      Technologies Evaluation Programme (MTEP), selected this device for evaluation and
      invited the manufacturer, JOTEC GmbH, to submit clinical and economic evidence.
      King's Technology Evaluation Centre (KiTEC), an External Assessment Centre (EAC)
      commissioned by the NICE, independently critiqued the manufacturer's submissions.
      The EAC considered that the manufacturer had included most of the relevant
      evidence for the E-vita open plus, based on international E-vita open registry
      data for 274 patients, but had provided only limited evidence for the
      comparators. The EAC therefore conducted a systematic review and meta-analysis of
      all comparators to supplement the information, and found ten additional studies
      providing outcome data for the three two-stage comparators. The EAC noted that
      the cost model submitted by the manufacturer did not include key complications
      during the procedures. The EAC developed a new economic model incorporating data
      on complications along with their long-term costs. The revised model indicated
      that the E-vita open plus might not provide cost savings when compared with some
      of the comparators in the short-term (1 year), but would have high cost savings
      in the long-term, from the second year onwards. The NICE Medical Technologies
      Guidance MTG 16, issued in December 2013, recommended the adoption of the E-vita
      open plus in selected patients within the National Health Service in England.

PMID- 25056416
TI  - Increasing prevalence of Coxiella burnetii seropositive Danish dairy cattle
      herds.
AB  - A study based on bulk tank milk samples from 120 randomly selected dairy cattle
      herds was conducted to estimate the prevalence of Coxiella burnetii seropositive
      dairy herds, to describe the geographical distribution, and to identify risk
      factors. Using the CHEKIT Q-fever Antibody ELISA Test Kit (IDEXX), the study
      revealed a prevalence of 79.2% seropositive herds, 18.3% seronegative herds, and
      2.5% serointermediate herds based on the instructions provided by the
      manufacturer. Multifactorial logistic regression showed statistically significant
      associations (P < 0.01) between C. burnetii seropositivity and increasing herd
      size (OR = 1.02 per cow increment) and increasing regional average number of
      cattle per dairy herd (OR = 1.02 per animal increment). Herds >150 cows had 17.9
      times higher odds of testing positive compared to herds <80 cows. The regional
      average number of cattle herds per square kilometer was borderline significantly
      related to the occurrence of seropositive dairy herds (P = 0.06). The results
      indicate an increased prevalence of seropositive dairy herds since the previous
      survey in 2008 and an adverse impact of increasing herd size and cattle density
      on the risk of seropositivity.

PMID- 25056417
TI  - Pyrene-based fluorescent supramolecular hydrogel: scaffold for energy transfer.
AB  - The self-assembled gelation of an amino-acid-based low molecular weight gelator
      having a pyrene moiety at the N terminus and a bis-ethyleneoxy unit linked with
      succinic acid at the C terminus is reported. This amphiphile is capable of
      gelating binary mixtures (1/3 v/v) of CH3CN/water, DMSO/water, and DMF/water, and
      the minimum gelation concentration (MGC) varied from 0.2 to 0.3% w/v. The sodium
      salt of the amphiphile efficiently gelates water with an MGC of 1.5% w/v. The
      participation of different noncovalent interactions in supramolecular gelation by
      formation of fibrillar networks was investigated by spectroscopic and microscopic
      methods. High mechanical strength of the supramolecular gels is indicated by
      storage moduli on the order of 10(3) Pa. The hydrogel was utilized for energy
      transfer, whereby inclusion of only 0.00075% w/v of acridine orange resulted in
      about 50% quenching of the fluorescence intensity of the gel through fluorescence
      resonance energy transfer.

PMID- 25056419
TI  - Stability studies on piroxicam encapsulated niosomes.
AB  - Drug delivery systems which yield ideal treatments are currently the center of
      interest for researchers. Niosomes have numerous advantages over other drug
      delivery systems. However, stability issue is not clear yet and is a serious
      drawback for niosomes. In this study, the stability of niosomes was the center of
      interest. Piroxicam which was chosen as the model drug was loaded to niosomes.
      Niosomes were prepared by thin-film method and different forms (aqueous
      dispersion, lyophilized powder and lyophilized powder with cryoprotectant) of the
      original niosome formulation were prepared. The samples were stored either at 5
      degrees C+/-3 degrees C or 25 degrees C+/-2 degrees C/60% RH+/-5% RH for 3
      months. The drug leakage percent, particle size and distribution, zeta potential,
      drug release profiles were determined and niosomes were visualized under optic
      microscope. Niosome formulation provided sustained release of piroxicam. The drug
      leakage from stored niosomes was observed at the level of 1.56-6.63 %. Individual
      vesicle images were obtained for all samples by optical microscope. However,
      particle size of niosomes was increased upon storage. The zeta potential values
      were neither related to time nor physical form. Drug release profiles and amounts
      were quite similar for all forms of niosomes and the original formulation but a
      slight decrease was noticed on drug release amounts by time. This indicates that
      niosomes become more rigid by time. Although the ideal storage was obtained with
      lyophilized niosomes at 5+/-3 degrees C in this study, the usage of suitable
      cryoprotectant and optimized lyophilization process should be further evaluated. 

PMID- 25056418
TI  - Genomic profiling of rice roots with short- and long-term chromium stress.
AB  - Cr(VI) is the most toxic valency form of Cr, but its toxicity targets and the
      cellular systems contributing to acquisition of tolerance remain to be resolved
      at the molecular level in plants. We used microarray assay to analyze the
      transcriptomic profiles of rice roots in response to Cr(VI) stress. Gene ontology
      analysis revealed that the 2,688 Cr-responsive genes were involved in binding
      activity, metabolic process, biological regulation, cellular process and
      catalytic activity. More transcripts were responsive to Cr(VI) during long-term
      exposure (24 h, 2,097 genes), than short-term exposure (1- and 3-h results
      pooled, 1,181 genes). Long-term Cr(VI)-regulated genes are involved in cytokinin
      signaling, the ubiquitin-proteasome system pathway, DNA repair and Cu
      transportation. The expression of AS2 transcription factors was specifically
      modulated by long-term Cr(VI) stress. The protein kinases receptor-like
      cytoplasmic kinase and receptor-like kinase in flowers 3 were significantly
      upregulated with only short-term Cr(VI) exposure. In addition, 4 mitogen
      activated protein kinase kinase kinases, 1 mitogen-activated protein kinase
      (MAPK) and 1 calcium-dependent protein kinase (CDPK) were upregulated with short
      term Cr(VI) treatment. Expression of reactive oxygen species and calcium and
      activity of MAPKs and CDPK-like kinases were induced with increasing Cr(VI)
      concentration. These results may provide new insights into understanding the
      mechanisms of Cr toxicity and tolerance during different stages in rice roots. 

PMID- 25056420
TI  - A lecture program on complementary and alternative medicine for cancer patients-
      evaluation of the pilot phase.
AB  - About half of all patients with cancer use complementary or alternative medicine
      (CAM). In 2013, we started a lecture program for patients, followed by evidence
      based recommendations on counseling on CAM. These recommendations have been
      published before by this working group. The aim of the program is to provide
      scientific facts on the most often used CAM methods in standardized presentations
      which help patients discuss the topic with their oncologists and support shared
      decision making. The article presents the evaluation of the pilot phase.
      Participants received a standardized questionnaire before the start of the
      lecture. The questionnaire comprises four parts: demographic data, data
      concerning experience with CAM, satisfaction with the lecture, and needs for
      further information on CAM. In 2013, seven lectures on CAM were given in
      cooperation with regional branches of the German Cancer Society in several German
      states. Four hundred sixty patients and relatives took part (75% females and 16%
      males). Forty-eight percent formerly had used CAM. Most often named sources of
      information on CAM were print media (48%) and the Internet (37%). Most
      participants rated additional written information valuable. About one third would
      like to have an individual consultation concerning CAM. A standardized
      presentation of evidence on CAM methods most often used, together with
      recommendations on the self-management of symptoms, is highly appreciated. The
      concept of a highly interactive lecture comprising is feasible and if presented
      in lay terminology, adequate. In order to give additional support on the topic,
      written information should be provided as the first step.

PMID- 25056421
TI  - A new method to pair-match metacarpals using bilateral asymmetry and shape
      analysis.
AB  - Matching pairs of skeletal elements is of fundamental importance when re
      associating skeletons from commingled settings. This study presents a new method
      that combines the use of traditional anthropometric size measurements and the
      analysis of shape, through geometric morphometrics, to form pairs from commingled
      settings. We tested the hypothesis that shape asymmetry among individuals is
      smaller than between individuals that share similar dimensions. The metacarpals
      were measured in their maximum length, and absolute means of asymmetry between
      right and left metacarpals were calculated. To analyze the shape characteristics,
      two-dimensional landmarks were recorded from digital images of 111 metacarpals.
      The specimens were analyzed using generalized Procrustes analysis and
      multivariate statistics. The accuracy of pair-matching bones using a combined
      method was of 100%, showing that the incorporation of geometric morphometrics
      techniques--in the assessment of shape in physical anthropology--is of particular
      use when comparing the shape differences/similarities between individuals.

PMID- 25056422
TI  - Benchmarking dispersion and geometrical counterpoise corrections for cost
      effective large-scale DFT calculations of water adsorption on graphene.
AB  - The physisorption of water on graphene is investigated with the hybrid density
      functional theory (DFT)-functional B3LYP combined with empirical corrections,
      using moderate-sized basis sets such as 6-31G(d). This setup allows to model the
      interaction of water with graphene going beyond the quality of classical or
      semiclassical simulations, while still keeping the computational costs under
      control. Good agreement with respect to Coupled Cluster with singles and doubles
      excitations and perturbative triples (CCSD(T)) results is achieved for the
      adsorption of a single water molecule in a benchmark with two DFT-functionals
      (Perdew/Burke/Ernzerhof (PBE), B3LYP) and Grimme's empirical dispersion and
      counterpoise corrections. We apply the same setting to graphene supported by
      epitaxial hexagonal boron nitride (h-BN), leading to an increased interaction
      energy. To further demonstrate the achievement of the empirical corrections, we
      model, entirely from first principles, the electronic properties of graphene and
      graphene supported by h-BN covered with different amounts of water (one, 10 water
      molecules per cell and full coverage). The effect of h-BN on these properties
      turns out to be negligibly small, making it a good candidate for a substrate to
      grow graphene on.

PMID- 25056423
TI  - Incidence and risk of atrial fibrillation in sleep-disordered breathing without
      coexistent systemic disease.
AB  - BACKGROUND: Although the link between sleep-disordered breathing (SDB) and atrial
      fibrillation (AF) has been reported, a population-based longitudinal cohort study
      was lacking. The goal of the present study was to investigate the AF risk carried
      by SDB, using the National Health Insurance Research Database in Taiwan. METHODS
      AND RESULTS: From 2000 to 2001, a total of 579,521 patients who had no history of
      cardiac arrhythmias or significant comorbidities were identified. Among them,
      4,082 subjects with the diagnosis of SDB were selected as the study group, and
      the remaining 575,439 subjects constituted the control group. The study endpoint
      was the occurrence of new-onset AF. During a follow-up of 9.2+/-2.0 years, there
      were 4,023 patients (0.7%) experiencing new-onset AF. The occurrence rate of AF
      was higher in patients with SDB compared to those without it (1.3% vs. 0.7%,
      P<0.001). The AF incidences were 1.38 and 0.76 per 1,000 person-years for
      patients with and without SDB, respectively. After anadjustment for age and sex,
      SDB was a significant risk factor of AF with a hazard ratio of 1.536. The AF risk
      increased with increasing clinical severity of SDB, represented by the
      requirement of continuous positive airway pressure use. CONCLUSIONS: SDB itself,
      without the coexistence of other systemic diseases, was a risk factor of AF.

PMID- 25056424
TI  - Better risk stratification for patients with complex coronary artery disease.

PMID- 25056425
TI  - Targeting of high peak respiratory exchange ratio is safe and enhances the
      prognostic power of peak oxygen uptake for heart failure patients.
AB  - BACKGROUND: Peak oxygen uptake (VO2) and ventilatory efficiency (VE/VCO2slope)
      measured on cardiopulmonary exercise testing (CPX) are prognostic indicators in
      heart failure (HF) patients, but peak VO2is influenced by patient effort. In CPX
      targeting a peak respiratory exchange ratio (pRER; an objective index of effort
      adequacy) higher than the commonly recommended level, we assessed the safety and
      prognostic value of CPX parameters compared with non-CPX parameters. METHODS AND
      RESULTS: We studied 283 consecutive HF patients with left ventricular ejection
      fraction (LVEF) <=45% (mean, 26.3%) who underwent CPX targeting pRER >1.20. The
      attained pRER (mean, 1.26) was consistently high irrespective of LVEF, and there
      was no major exercise-related adverse event. The composite of all-cause death or
      HF hospitalization occurred in 111 patients (39%) during a median follow-up of 47
      months. Among well-known prognostic markers, peak VO2was the most powerful
      predictor of outcome as both a continuous and an optimal dichotomous variable,
      followed by VE/VCO2slope. On multivariate analysis, peak VO2was a significant
      independent predictor, whereas VE/VCO2slope, B-type natriuretic peptide, and LVEF
      were not. CONCLUSIONS: In CPX targeting pRER >1.20 for HF patients, peak VO2is
      the most powerful among well-known predictors, without an increased risk of
      exercise-related events. These findings advocate a high target pRER in CPX even
      in advanced HF.

PMID- 25056426
TI  - Prevalence, predictors and prognosis of patients with heart failure requiring
      nursing care.
AB  - BACKGROUND: Although the need for nursing care (NC) in heart failure (HF)
      patients is recognized, detailed information on the current status in Japan is
      lacking. METHODS AND RESULTS: In the CHART-2 Study, we obtained information on
      daily life, physical ability, nutrition and mental status for 4,174 patients
      (mean age, 67.1+/-10.8 years; 73.3% male) out of 10,219 patients. We examined the
      prevalence, baseline characteristics and clinical outcomes of stage B and C/D HF
      patients requiring NC. The prevalence of HF requiring NC was significantly higher
      in stage C/D (38.6%) than in stage B (30.4%; P<0.001). Among the reasons for
      requiring NC, physical dysfunction was most prevalent in both stage B (20.6%) and
      C/D (29.0%). Compared with the non-NC group, the NC group was characterized by
      higher age, higher prevalence of female gender and cerebrovascular disease, and
      increased plasma brain natriuretic peptide regardless of HF stage. During a
      median follow-up of 12.7 months after the survey, the NC group had a
      significantly higher mortality compared with the non-NC group (9.6% vs. 3.6%,
      P<0.001). On multivariate logistic analysis depressive mental status (hazard
      ratio [HR], 3.61; P<0.001) and dementia (HR, 2.70; P<0.001) were significantly
      associated with NC need. CONCLUSIONS: In HF patients, NC need is considerably
      high and is associated with increased mortality regardless of HF stage in Japan.

PMID- 25056427
TI  - SNP-SIG 2013: from coding to non-coding--new approaches for genomic variant
      interpretation.

PMID- 25056428
TI  - Renal vein reconstruction for primary leiomyosarcoma of the inferior vena cava.

PMID- 25056429
TI  - Mechanochemical C-H bond activation: rapid and regioselective double
      cyclopalladation monitored by in situ Raman spectroscopy.
AB  - The first direct mechanochemical transition-metal-mediated activation of strong
      phenyl C-H bonds is reported. The mechanochemical procedure, resulting in
      cyclopalladated complexes, is quantitative and significantly faster than solution
      synthesis and allows highly regioselective activation of two C-H bonds by
      palladium(II) acetate in asymmetrically substituted azobenzene. Milling is
      monitored by in situ solid-state Raman spectroscopy which in combination with
      quantum-chemical calculations enabled characterization of involved reaction
      species, direct insight into the dynamics and reaction pathways, as well as the
      optimization of a milling process.

PMID- 25056430
TI  - Increase GP trainees by 450 a year to avoid crisis, says taskforce.

PMID- 25056431
TI  - The challenges of real-world implementation of web-based shared care software:
      the HopSCOTCH Shared-Care Obesity Trial in Children.
AB  - BACKGROUND: E-health initiatives hold promise to improve shared-care models of
      health care. In 2008-2011 we developed and trialled web-based software to
      facilitate a randomised trial of a shared-care approach for childhood obesity
      involving General Practitioners (GPs) working with tertiary specialists. We
      describe the software's development, implementation and evaluation, and make
      recommendations for future e-health initiatives. The web-based software was
      designed with the goals of allowing both GPs and specialists to communicate and
      review patient progress; integrating with existing GP software; and supporting
      GPs to deliver the structured intervention. Specifically, we aimed to highlight
      the challenges inherent in this process, and report on the extent to which the
      software ultimately met its implementation and user aims. METHODS: The study was
      conducted at the Royal Children's Hospital and 22 general practices across
      Melbourne, Australia. Participants comprised 30 GPs delivering the shared-care
      intervention. Outcomes included the following. (1) GPs' pre-specified software
      requirements: transcribed from two focus groups and analysed for themes using
      content analysis. (2) Software implementation and performance based on the
      experience of the research team and GPs. (3) GP users' evaluation collected via
      questionnaire. (4) Software usage collected via GP questionnaire and qualified
      through visual inspection of the software meta-data. RESULTS: Software
      implementation posed difficult and at times disabling technological barriers
      (e.g. out-dated hardware, poor internet connections). The software's speed and
      inability to seamlessly link with day-to-day software was a source of
      considerable frustration. Overall, GPs rated software usability as poor, although
      most (68%) felt that the structure and functionality of the software was useful.
      Recommendations for future e-health initiatives include thorough scoping of IT
      systems and server speed, testing across diverse environments, automated pre
      requisite checks and upgrades of processors/memory where necessary, and user
      created usernames and passwords. CONCLUSIONS: GPs are willing to embrace novel
      technologies to support their practice. However, implementation remains
      challenging mainly for technical reasons, and this precludes further evaluation
      of potential user-specific barriers. These findings could inform future e-health
      ventures into shared-care, and highlight the need for an appropriate
      infrastructure. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry: ACTRN126080000553.

PMID- 25056432
TI  - Rho GTPase Rac1: molecular switch within the galectin network and for N-glycan
      alpha2,6-sialylation/O-glycan core 1 sialylation in colon cancer in vitro.
AB  - The Rho GTPase Rac1 is a multifunctional protein working through different
      effector pathways. The emerging physiological significance of glycanlectin
      recognition gives reason to testing the possibility for an influence of
      modulation of Rac1 expression on these molecular aspects. Using human colon
      adenocarcinoma (SW620) cells genetically engineered for its up- and down
      regulation (Rac1+ and Rac1- cells) along with wild-type and mock-transfected
      control cells, the questions are addressed whether the presence of
      adhesion/growth-regulatory galectins and distinct aspects of cell surface
      glycosylation are affected. Proceeding from RT-PCR data to Western blotting after
      two-dimensional gel electrophoresis and flow cytofluorimetry with non
      crossreactive antibodies against six members of this lectin family (i.e.
      galectins-1, -3, -4, -7, -8 and -9), a reduced extent of the presence of
      galectins-1, -7 and -9 was revealed in the case of Rac1? cells. Application of
      these six galectins as probes to determination of cell reactivity for human
      lectins yielded relative increases in surface labelling of Rac1- cells with
      galectins-1, -3 and -7. Examining distinct aspects of cell surface glycosylation
      with a panel of 14 plant/fungal lectins disclosed a decrease in alpha2,6
      sialylation of N-glycans and an increase in PNA-reactive sites (i.e. non
      sialylated core 1 O-glycans), two alterations known to favour reactivity for
      galectins-1 and -3. Thus, manipulation of Rac1 expression selectively affects the
      expression pattern within the galectin network at the level of proteins and
      distinct aspects of cell surface glycosylation. 

PMID- 25056433
TI  - An association between MPO -463 G/A polymorphism and type 2 diabetes.
AB  - Myeloperoxidase (MPO) is an enzyme which is a member of the haem-peroxidase
      superfamily and plays a role in production of reactive oxygen species. The most
      common polymorphism in the promoter region of MPO gene is -463 G/A. It was shown
      that carrying the GG genotype means increased activity of the gene approximately
      2-3-fold compared to GA and AA genotypes. It was found that hyperglycaemia,
      modified oxidized proteins and increased advanced glycosylated end products (AGE)
      are related to oxidative stress in diabetes. Under the hyperglycaemic conditions,
      production of reactive oxygen radical is elevated in smooth muscle endothelial
      cells, mesengial and tubular endothelial cells. Especially, elevated lipid
      oxidation plays an important role in pathogenesis of diabetic complications such
      as cardiovascular complications. We examined the MPO -463 G/A polymorphism by
      using the PCR-RFLP method in 145 type 2 diabetic patients and 151 healthy
      controls. We observed that the AA genotype and A allele were protective variants
      against type 2 diabetes and the GG genotype was a risk factor for diabetes. While
      we studied the relationship between genotypes and biochemical parameters, we
      found that patients with the A allele had decreased serum cholesterol,
      triglyceride, VLDL levels and body mass index. We suggest that the MPO gene has
      an important role in pathogenesis of type 2 diabetes because of the increased
      frequency of GG genotype, which is related to increased activity and oxidant
      capacity of MPO in the patients. 

PMID- 25056434
TI  - Differential expression and processing of matrix metalloproteinase 19 marks
      progression of gastrointestinal diseases.
AB  - Matrix metalloproteinases (MMPs), responsible for extracellular matrix
      remodelling and processing of numerous soluble and cell-surface proteins, appear
      to play important roles in pathogenesis of gastrointestinal diseases. MMPs
      influence migration of inflammatory cells, mucosal destruction, matrix deposition
      and degradation. In this study, we analysed the expression of MMP-19 in the main
      forms of gastrointestinal diseases including inflammatory bowel diseases (IBD)
      such as ulcerative colitis and Crohn's disease, and colorectal carcinoma. We
      identified prominent MMP-19 expression in unaffected areas of intestinal
      epithelia and macrophages but not in other cells or tissues. Abundant expression
      of MMP-19 was also found in the endothelium of blood and lymphatic vessels of
      inflamed intestinal tissue. High MMP-19 immunoreactivity was also associated with
      macrophages in inflamed areas and myenteric plexuses. In comparison to the
      intestinal epithelium, all these cell types and compartments appeared to express
      MMP-19 irrespective of the disease pathogenesis and progression. Intestinal
      epithelia exhibited striking differential immunoreactivity for MMP-19. While
      immunoreactivity of monoclonal antibody recognizing the propeptide domain
      declined in virtually all IBD and colorectal carcinoma samples, other polyclonal
      antibodies against the hinge region and propetide domain did not show such an
      obvious decrease. Additional Western blotting analysis revealed that the
      antibodies against MMP-19 recognize differently processed forms of this MMP. The
      disappearance of immunoreactivity of the monoclonal anti-propeptide domain
      antibody does not mean down-regulation of MMP-19, but processing of the immature
      form. As this processing likely leads to the activation of this MMP, the
      differential staining pattern may be an important sign of disease progression. 

PMID- 25056435
TI  - Time course of cerebral hypoperfusion-induced neurodegenerative changes in the
      cortex of male and female rats.
AB  - To study time-dependent and gender-specific intracellular and biochemical
      mechanisms that lead to neurodegeneration due to moderate but persistent
      reduction of cerebral blood flow, adult male and female Wistar rats were divided
      into two main groups - controls that underwent sham operation and animals
      subjected to permanent bilateral occlusion of common carotid arteries. Animals
      were sacrificed 3, 7 or 90 days following the insult. Expression of several
      apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and
      DNA fragmentation assay were used to estimate the apoptotic processes and
      potential neurodegeneration in cerebral cortex. Data suggest a time-specific
      increase of Bax as well as time- and gender-associated downregulation in protein
      expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased
      cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but
      not gender-specific neurodegeneration was observed. Our findings support the
      concept of time- and gender-associated response to permanent bilateral occlusion
      of common carotid arteries, which would enable better understanding of the
      mechanisms underlying cerebral hypoperfusion. 

PMID- 25056436
TI  - HNF-4alpha regulates expression of human ornithin carbamoyltransferase through
      interaction with two positive cis-acting regulatory elements located in the
      proximal promoter.
AB  - OTC encodes ornithine carbamoyltransferase, mitochondrial matrix enzyme involved
      in the synthesis of urea. The tissue-specific expression of OTC in the liver and
      intestine is dependent on the interaction of OTC promoter with an upstream
      enhancer. HNF-4 and C/EBPbeta are crucial for this interaction in the rat and
      mouse. In the present study we focused on characterization of elements involved
      in the regulation of OTC transcription in human. Using a set of 5'-deleted
      promoter mutants in a reporter assay we identified two positive cis-acting
      regulatory elements located at c.-105 and c.-136 within the human OTC promoter.
      Both are essential for the transcriptional activity of the promoter itself and
      for the interaction with the enhancer. Protein binding at the corresponding sites
      was confirmed by DNase I footprinting. Electromobility shift assay with a
      specific competitor and anti-HNF-4alpha antibody identified the DNA-protein
      binding sites as HNF-4alpha recognition motifs. A third HNF-4alpha binding site
      has been found at the position c.-187. All three HNF-4alpha binding sites are
      located within 35 bp upstream of the transcription start sites at positions c.
      95, c.-119 (major) and c.-169 (minor). A series of C/EBPbeta recognition motifs
      was identified within the enhancer. Involvement of C/EBPbeta and HNF-4alpha in
      the promoter-enhancer interaction is further supported by a massive DNAprotein
      interaction observed in the footprinting and EMSA assays. Since the OTC promoter
      lacks general core promoter elements such as TATA-box or initiators in standard
      positions, HNF-4alpha most likely plays an essential role in the initiation of
      OTC transcription in human. 

PMID- 25056437
TI  - Differential expression of tripartite motif-containing family in normal human
      dermal fibroblasts in response to porcine endogenous retrovirus infection.
AB  - Antiretroviral restriction factors may play an essential role in the safety of
      xenotransplantation. Therefore, the present study focused on investigation of the
      changes in the tripartite motif-containing family (TRIM) gene expression in
      normal human dermal fibroblasts with and without lipopolysaccharide stimulation
      in response to porcine endogenous retrovirus infection. Analysis of the
      expression profile of TRIMs was performed using oligonucleotide microarrays and
      QRT-PCR. Nine (TRIM1, TRIM2, TRIM5, TRIM14, TRIM16, TRIM18, TRIM22, TRIM27 and
      TRIM31) statistically significantly differentially expressed genes were found (P
      < 0.05, one-way ANOVA). In conclusion, comprehensive analysis of retroviral
      restriction factor gene expression in human dermal fibroblasts before and after
      porcine endogenous retrovirus infection with and without LPS stimulation may
      suggest association of the selected TRIMs with antiretroviral activity. 

PMID- 25056438
TI  - Brown adipose tissue improves whole-body glucose homeostasis and insulin
      sensitivity in humans.
AB  - Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic
      tissue owing to its ability to dissipate energy as heat. Despite a plethora of
      data concerning the role of BAT in glucose metabolism in rodents, the role of BAT
      (if any) in glucose metabolism in humans remains unclear. To investigate whether
      BAT activation alters whole-body glucose homeostasis and insulin sensitivity in
      humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-))
      men under thermoneutral conditions and after prolonged (5-8 h) cold exposure
      (CE). The two groups were similar in age, BMI, and adiposity. CE significantly
      increased resting energy expenditure, whole-body glucose disposal, plasma glucose
      oxidation, and insulin sensitivity in the BAT(+) group only. These results
      demonstrate a physiologically significant role of BAT in whole-body energy
      expenditure, glucose homeostasis, and insulin sensitivity in humans, and support
      the notion that BAT may function as an antidiabetic tissue in humans.

PMID- 25056440
TI  - Subarachnoid hemorrhage secondary to a ruptured middle cerebral aneurysm in a
      patient with osteogenesis imperfecta: a case report.
AB  - BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited
      disorders that occur owing to the abnormalities in type 1 collagen, and is
      characterized by increased bone fragility and other extraskeletal manifestations.
      We report the case of a patient who was diagnosed with OI following subarachnoid
      hemorrhage (SAH) secondary to a ruptured saccular intracranial aneurysm (IA).
      CASE PRESENTATION: A 37-year-old woman was referred to our hospital because of
      sudden headache and vomiting. She was diagnosed with SAH (World Federation of
      Neurosurgical Society grade 2) owing to an aneurysm of the middle cerebral
      artery. She then underwent surgical clipping of the aneurysm successfully. She
      had blue sclerae, a history of several fractures of the extremities, and a family
      history of bone fragility and blue sclerae in her son. According to these
      findings, she was diagnosed with OI type 1. We performed genetic analysis for a
      single nucleotide G/C polymorphism (SNP) of exon 28 of the gene encoding for
      alpha-2 polypeptide of collagen 1, which is a potential risk factor for IA.
      However, this SNP was not detected in this patient or in five normal control
      subjects. Other genetic analyses did not reveal any mutations of the COL1A1 or
      COL1A2 gene. The cerebrovascular system is less frequently involved in OI. OI is
      associated with increased vascular weakness owing to collagen deficiency in and
      around the blood vessels. SAH secondary to a ruptured IA with OI has been
      reported in only six cases. CONCLUSION: The patient followed a good clinical
      course after surgery. It remains controversial whether IAs are caused by OI or
      IAs are coincidentally complicated with OI.

PMID- 25056439
TI  - Targeted reduction of vascular Msx1 and Msx2 mitigates arteriosclerotic
      calcification and aortic stiffness in LDLR-deficient mice fed diabetogenic diets.
AB  - When fed high-fat diets, male LDLR(-/-) mice develop obesity, hyperlipidemia,
      hyperglycemia, and arteriosclerotic calcification. An osteogenic Msx-Wnt
      regulatory program is concomitantly upregulated in the vasculature. To better
      understand the mechanisms of diabetic arteriosclerosis, we generated SM22
      Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) mice, assessing the impact of Msx1+Msx2
      gene deletion in vascular myofibroblast and smooth muscle cells. Aortic Msx2 and
      Msx1 were decreased by 95% and 34% in SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-)
      animals versus Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) controls, respectively. Aortic
      calcium was reduced by 31%, and pulse wave velocity, an index of stiffness, was
      decreased in SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) mice vs. controls.
      Fasting blood glucose and lipids did not differ, yet SM22
      Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) siblings became more obese. Aortic
      adventitial myofibroblasts from SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) mice
      exhibited reduced osteogenic gene expression and mineralizing potential with
      concomitant reduction in multiple Wnt genes. Sonic hedgehog (Shh) and Sca1,
      markers of aortic osteogenic progenitors, were also reduced, paralleling a 78%
      reduction in alkaline phosphatase (TNAP)-positive adventitial myofibroblasts. RNA
      interference revealed that although Msx1+Msx2 supports TNAP and Wnt7b expression,
      Msx1 selectively maintains Shh and Msx2 sustains Wnt2, Wnt5a, and Sca1 expression
      in aortic adventitial myofibroblast cultures. Thus, Msx1 and Msx2 support
      vascular mineralization by directing the osteogenic programming of aortic
      progenitors in diabetic arteriosclerosis.

PMID- 25056441
TI  - The perspectives of Aboriginal patients and their health care providers on
      improving the quality of hemodialysis services: a qualitative study.
AB  - Chronic kidney disease has a higher prevalence in Indigenous populations
      globally. The incidence of end-stage kidney disease in Australian Aboriginal
      people is eight times higher than non-Aboriginal Australians. Providing services
      to rural and remote Aboriginal people with chronic disease is challenging because
      of access and cultural differences. This study aims to describe and analyze the
      perspectives of Aboriginal patients' and health care providers' experience of
      renal services, to inform service improvement for rural Aboriginal hemodialysis
      patients. We conducted a thematic analysis of interviews with Aboriginal patients
      (n = 18) receiving hemodialysis in rural Australia and health care providers
      involved in their care (n = 29). An overarching theme of avoiding the "costly"
      crisis encompassed four subthemes: (1) Engaging patients earlier (prevent late
      diagnosis, slow disease progression); (2) flexible family-focused care (early
      engagement of family, flexibility to facilitate family and cultural obligations);
      (3) managing fear of mainstream services (originating in family dialysis
      experiences and previous racism when engaging with government organizations); (4)
      service provision shaped by culture (increased home dialysis, Aboriginal support
      and Aboriginal-led cultural education). Patients and health care providers
      believe service redesign is required to meet the needs of Aboriginal hemodialysis
      patients. Participants identified early screening and improving the relationship
      of Aboriginal people with health systems would reduce crisis entry to
      hemodialysis. These strategies alongside improving the cultural competence of
      staff would reduce patients' fear of mainstream services, decrease the current
      emotional and family costs of care, and increase efficiency of health expenditure
      on a challenging and increasingly unsustainable treatment system. 

PMID- 25056442
TI  - Management of patients with HER2-positive metastatic breast cancer: is there an
      optimal sequence of HER2-directed approaches?
AB  - The successful development of therapies targeting the human epidermal growth
      factor receptor 2 (HER2) has altered the natural progression of disease among
      patients with HER2-positive metastatic breast cancer. The monoclonal antibody
      trastuzumab was the first HER2-directed agent and it was associated with
      significantly improved outcomes for patients. Subsequently, other HER2-directed
      agents such as the monoclonal antibody pertuzumab, the tyrosine kinase receptor
      inhibitor lapatinib, and the immunoconjugate trastuzumab emtansine were developed
      to overcome resistance to trastuzumab and provide additional treatment options
      for patients. Recent data have demonstrated that the use of these HER2-directed
      agents improves outcomes. However, with the emergence of new HER2-targeted
      agents, the optimal sequencing of treatment remains unclear. Ongoing research is
      investigating new HER2 combinations, the role of sequencing, novel HER2-directed
      agents, and combinations with other targeted agents to overcome resistance.

PMID- 25056443
TI  - Clinical course after corticosteroid therapy in IgG4-related
      aortitis/periaortitis and periarteritis: a retrospective multicenter study.
AB  - INTRODUCTION: Immunoglobulin G4 (IgG4)-related aortitis/periaortitis and
      periarteritis are vascular manifestations of IgG4-related disease. In this
      disease, the affected aneurysmal lesion has been suspected to be at risk of
      rupture. In this study, we aimed to clarify the clinical course after
      corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis.
      METHODS: We retrospectively evaluated clinical features, including laboratory
      data, imaging findings and the course after corticosteroid therapy, in 40
      patients diagnosed with IgG4-related aortitis/periaortitis and periarteritis on
      the basis of periaortic/periarterial radiological findings, satisfaction of the
      comprehensive diagnostic criteria or each organ-specific diagnostic criteria, and
      exclusion of other diseases. RESULTS: The patients were mainly elderly, with an
      average age of 66.4 years and with a marked male predominance and extensive other
      organ involvement. Subjective symptoms were scanty, and only a small proportion
      had elevated serum C-reactive protein levels. The affected aorta/artery were the
      abdominal aortas or the iliac arteries in most cases. Thirty-six patients were
      treated with prednisolone, and the periaortic/periarterial lesions improved in
      most of them during the follow-up period. Two (50.0%) of four patients with
      luminal dilatation of the affected lesions before corticosteroid therapy had
      exacerbations of luminal dilatation after therapy, whereas none of the twenty-six
      patients without it had a new appearance of luminal dilatation after therapy.
      CONCLUSIONS: The results of this retrospective multicenter study highlight three
      important points: (1) the possibility of latent existence and progression of
      periaortic/periarterial lesions, (2) the efficacy of corticosteroid therapy in
      preventing new aneurysm formation in patients without luminal dilatation of
      periaortic/periarterial lesions and (3) the possibility that a small proportion
      of patients may actually develop luminal dilatation of periaortic/periarterial
      lesions in IgG4-related aortitis/periaortitis and periarteritis. A larger-scale
      prospective study is required to confirm the efficacy and safety of
      corticosteroid therapy in patients with versus those without luminal dilatation
      and to devise a more useful and safe treatment strategy, including administration
      of other immunosuppressants.

PMID- 25056444
TI  - Prior experience with a pain stimulus as a predictor of placebo analgesia.
AB  - Placebo effects are important in pain reduction, but the effects are
      inconsistent. Prior experience with a pain stimulus may moderate placebo
      analgesia. The current study tests the effect of prior experience with a pain
      stimulus on placebo analgesia during a laboratory pain task. Healthy normotensive
      undergraduates (66 women, 68 men) who either did or did not report prior
      experience with pain from submerging a limb in cold water were enrolled. In the
      laboratory, an experimenter applied an inert, medicinal-smelling cream to
      participants' non-dominant hand. Participants randomized to the no-expectation
      group were told that the cream was a hand cleanser. Participants randomized to
      the placebo expectation group were told that the cream would reduce the pain
      associated with the cold pressor task. Participants then completed the cold
      pressor task and reported their pain on the short form of the McGill Pain
      Questionnaire. Analysis of variance revealed a main effect of expectation (p <
      .05), such that participants in the placebo expectation group reported less pain.
      An interaction was also found between expectation and prior experience (p < .05),
      such that participants with prior experience with pain from cold water immersion
      showed no difference in pain reports between expectation groups. In a pain
      context, prior experience with the pain stimulus may prevent a placebo
      expectation from reducing the experience of pain. 

PMID- 25056445
TI  - Conformational equilibria and large-amplitude motions in dimers of carboxylic
      acids: rotational spectrum of acetic acid-difluoroacetic acid.
AB  - We report the rotational spectra of two conformers of the acetic acid
      difluoroacetic acid adduct (CH3COOH-CHF2COOH) and supply information on its
      internal dynamics. The two conformers differ from each other, depending on the
      trans or gauche orientation of the terminal -CHF2 group. Both conformers display
      splittings of the rotational transitions, due to the internal rotation of the
      methyl group of acetic acid. The corresponding barriers are determined to be
      V3(trans)=99.8(3) and V3(gauche)=90.5(9) cm(-1) (where V3 is the methyl rotation
      barrier height). The gauche form displays a further doubling of the rotational
      transitions, due to the tunneling motion of the -CHF2 group between its two
      equivalent conformations. The corresponding B2 barrier is estimated to be 108(2)
      cm(-1). The increase in the distance between the two monomers upon OH->OD
      deuteration (the Ubbelohde effect) is determined.

PMID- 25056446
TI  - Little agreement in GOLD category using CAT and mMRC in 450 primary care COPD
      patients in New Zealand.

PMID- 25056448
TI  - Diversity in the preimmune immunoglobulin repertoire of SHR lines susceptible and
      resistant to end-organ injury.
AB  - We used next-generation sequencing to identify immunoglobulin heavy chain (IGH)
      genetic variation in two closely related hypertensive rat lines that differ in
      susceptibility to end-organ disease (SHR-A3 and SHR-B2). The two SHR lines differ
      extensively at the IGH locus from the rat reference genome sequence and from each
      other, creating 306 sequence unique IGH genes. Compared with IGH genes mapped in
      the rat reference genome sequence, 98 are null gene alleles (31 are null in both
      SHR lines, 45 are null in SHR-A3 only and 23 are null in SHR-B2 only). Of the 306
      divergent gene sequences, 126 result in amino acid substitution and, among these,
      SHR-A3 and SHR-B2 differ from one another at the amino acid level in 96 segments.
      Twelve pseudogenes in the rat reference genome sequence had changes displacing
      the stop codon and creating probable functional genes in either or both SHR-A3
      and SHR-B2. A further five alleles that encoded functional rat reference genome
      sequence genes or open reading frames were converted to pseudogenes in either or
      both SHR-A3 and SHR-B2. These studies reveal that the preimmune immunoglobulin
      repertoire is highly divergent among SHR lines differing in end-organ injury
      susceptibility and this may modify immune mechanisms in hypertensive renal
      injury. 

PMID- 25056449
TI  - Letter regarding the article "Growth differentiation factor-15 in takotsubo
      cardiomyopathy: diagnostic and prognostic value".

PMID- 25056447
TI  - Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and
      TGF-beta.
AB  - The prevalence of allergic diseases has significantly increased in industrialized
      countries. Allergen-specific immunotherapy (AIT) remains as the only curative
      treatment. The knowledge about the mechanisms underlying healthy immune responses
      to allergens, the development of allergic reactions and restoration of
      appropriate immune responses to allergens has significantly improved over the
      last decades. It is now well-accepted that the generation and maintenance of
      functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg)
      cells are essential for healthy immune responses to environmental proteins and
      successful AIT. Treg cells comprise different subsets of T cells with suppressive
      capacity, which control the development and maintenance of allergic diseases by
      various ways of action. Molecular mechanisms of generation of Treg cells, the
      identification of novel immunological organs, where this might occur in vivo,
      such as tonsils, and related epigenetic mechanisms are starting to be deciphered.
      The key role played by the suppressor cytokines interleukin (IL)-10 and
      transforming growth factor (TGF)-beta produced by functional Treg cells during
      the generation of immune tolerance to allergens is now well established. Treg and
      Breg cells together have a role in suppression of IgE and induction of IgG4
      isotype allergen-specific antibodies particularly mediated by IL-10. Other cell
      types such as subsets of dendritic cells, NK-T cells and natural killer cells
      producing high levels of IL-10 may also contribute to the generation of healthy
      immune responses to allergens. In conclusion, better understanding of the immune
      regulatory mechanisms operating at different stages of allergic diseases will
      significantly help the development of better diagnostic and predictive biomarkers
      and therapeutic interventions. 

PMID- 25056450
TI  - Pre-clinical analysis of changes in intra-cellular biochemistry of glioblastoma
      multiforme (GBM) cells due to c-Myc silencing.
AB  - Glioblastoma Multiforme (GBM) is an aggressive form of brain Tumor that has few
      cures. In this study, we analyze the anti-proliferative effects of a new molecule
      JQ1 against GBMs induced in Wistar Rats. JQ1 is essentially a Myc inhibitor. c
      Myc is also known for altering the biochemistry of a tumor cell. Therefore, the
      study is intended to analyze certain other oncogenes associated with c-Myc and
      also the change in cellular biochemistry upon c-Myc inhibition. The quantitative
      analysis of gene expression gave a co-expressive pattern for all the three genes
      involved namely; c-Myc, Bcl-2, and Akt. The cellular biochemistry analysis by
      transmission electron microscopy revealed high glycogen and lipid aggregation in
      Myc inhibited cells and excessive autophagy. The study demonstrates the role of c
      Myc as a central metabolic regulator and Bcl-2 and Akt assisting in extending c
      Myc half-life as well as in regulation of autophagy, so as to regulate cell
      survival on the whole. The study also demonstrates that transient treatment by
      JQ1 leads to aggressive development of tumor and therefore, accelerating death,
      emphasizing the importance of dosage fixation, and duration for clinical use in
      future.

PMID- 25056451
TI  - Niobium(V) saponite clay for the catalytic oxidative abatement of chemical
      warfare agents.
AB  - A Nb(V)-containing saponite clay was designed to selectively transform toxic
      organosulfur chemical warfare agents (CWAs) under extremely mild conditions into
      nontoxic products with reduced environmental impact. Thanks to the insertion of
      Nb(V) sites within the saponite framework, a bifunctional catalyst with strong
      oxidizing and acid properties was obtained. Remarkable activity and high
      selectivity were observed for the oxidative abatement of (2-chloroethyl)ethyl
      sulfide (CEES), a simulant of sulfur mustard, at room temperature with aqueous
      hydrogen peroxide. This performance was significantly better compared to a
      conventional commercial decontamination powder.

PMID- 25056452
TI  - Hydrogen-bonded clusters of ferrocenecarboxylic acid on Au(111).
AB  - Self-assembled monolayers of ferrocenecarboxylic acid (FcCOOH) contain two
      fundamental units, both stabilized by intermolecular hydrogen bonding: dimers and
      cyclic five-membered catemers. At surface coverages below a full monolayer,
      however, there is a significantly more varied structure that includes double-row
      clusters containing two to twelve FcCOOH molecules. Statistical analysis shows a
      distribution of cluster sizes that is sharply peaked compared to a binomial
      distribution. This rules out simple nucleation-and-growth mechanisms of cluster
      formation, and strongly suggests that clusters are formed in solution and
      collapse into rows when deposited on the Au(111) surface. 

PMID- 25056453
TI  - Platelet volume and plateletcrit in dogs with presumed primary immune-mediated
      thrombocytopenia.
AB  - BACKGROUND: Mean platelet volume (MPV) and plateletcrit (PCT) are indices used in
      evaluating immune-mediated thrombocytopenia (IMT) in humans and in dogs with
      congenital macrothrombocytopenia. These indices may provide clinically valuable
      information in acquired thrombocytopenia. HYPOTHESIS/OBJECTIVES: Dogs with
      presumed primary IMT will have increased MPV, and therefore platelet mass (PCT)
      will increase faster than platelet count (PLT) during recovery. ANIMALS: Forty
      nine dogs with automated PLT < 30,000/MUL because of presumed primary IMT and
      hematocrit (HCT), PCT, MPV, and platelet distribution width determined from the
      same complete blood count (CBC), and 46 healthy controls. METHODS: Case-control
      retrospective study; PLT, PCT, MPV, and platelet distribution width (PDW) were
      recorded from CBCs from 49 dogs, with 45 having data collected on the day of
      presentation. Fifteen were confirmed to have attained a PLT >= 75,000/MUL on at
      least 1 CBC within 15 days after admission. The PCT equivalent to a PLT of
      75,000/MUL (assuming an average MPV) was calculated for comparison with PLT in
      terms of time to achieve a threshold of platelet mass by the 2 measures. RESULTS:
      Mean platelet volume was higher in IMT dogs (17.3 fl) than the reference
      population (10.5 fl) (P < .0001). The PDW was not significantly different among
      the groups. The median time for PCT to reach threshold in confirmed responders
      was faster (3 days) compared with PLT (4 days). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Immune-mediated thrombocytopenia is characterized by increased MPV.
      Time to achieve a threshold PCT tended to be shorter than PLT, suggesting that
      PCT may be a useful platelet parameter for monitoring dogs with IMT.

PMID- 25056454
TI  - Continuous infusion of recombinant activated factor VII for bleeding control
      after lobectomy in a patient with inherited factor VII deficiency.
AB  - Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation
      disorder with limited available information, especially in patients undergoing
      major thoracic surgery. In addition, an optimal management strategy for the
      disease has not been defined. We herein report a case involving a 61-year-old man
      with asymptomatic FVII deficiency who underwent a right middle and lower
      lobectomy to treat lung cancer. To the best of our knowledge, the present report
      is the first to describe the use of recombinant activated FVII continuous
      infusion for bleeding control after a major thoracic surgery in a patient with
      inherited FVII deficiency. 

PMID- 25056455
TI  - Thoracic endovascular aortic repair for patent ductus arteriosus in an elderly
      patient with congestive heart failure.
AB  - In elderly patients, open surgery for patent ductus arteriosus (PDA) is more
      difficult than that in children and often requires a cardiopulmonary bypass. We
      report the case of a 67-year-old patient with a PDA that was successfully treated
      with thoracic endovascular aortic repair (TEVAR). The patient was diagnosed with
      congestive heart failure (ejection fraction, 36 %) and PDA (9.7 mm in diameter).
      TEVAR was successfully performed to exclude the PDA. After TEVAR, the patient's
      heart failure was well controlled by diuretics. TEVAR may be a good alternative
      to open surgery.

PMID- 25056457
TI  - Dynamics of the NbCl5-catalyzed cycloaddition of propylene oxide and CO2 :
      assessing the dual role of the nucleophilic Co-catalysts.
AB  - A mechanistic study on the synthesis of propylene carbonate (PC) from CO2 and
      propylene oxide (PO) catalyzed by NbCl5 and organic nucleophiles such as 4
      dimethylaminopyridine (DMAP) or tetra-n-butylammonium bromide (NBu4 Br) is
      reported. A combination of in situ spectroscopic techniques and kinetic studies
      has been used to provide detailed insight into the reaction mechanism, the
      formation of intermediates, and interactions between the reaction partners. The
      results of DFT calculations support the experimental observations and allow us to
      propose a mechanism for this reaction. 

PMID- 25056456
TI  - Antifibrotic effects of KS370G, a caffeamide derivative, in renal ischemia
      reperfusion injured mice and renal tubular epithelial cells.
AB  - Accumulating evidence suggests that renal tubulointerstitial fibrosis is a main
      cause of end-stage renal disease. Clinically, there are no beneficial treatments
      that can effectively reverse the progressive loss of renal functions. Caffeic
      acid phenethyl ester is a natural phenolic antifibrotic agent, but rapid
      decomposition by an esterase leads to its low bioavailability. In this study, we
      evaluated the effects of KS370G, a caffeic acid phenylethyl amide, on murine
      renal fibrosis induced by unilateral renal ischemia-reperfusion injury (IRI) and
      in TGF-beta1 stimulated renal tubular epithelial cells (NRK52E and HK-2). In the
      animal model, renal fibrosis was evaluated at 14 days post-operation. Immediately
      following the operation, KS370G (10 mg/kg) was administered by oral gavage once a
      day. Our results show that KS370G markedly attenuates collagen deposition and
      inhibits an IRI-induced increase of fibronectin, vimentin, alpha-SMA and TGF
      beta1 expression and plasma TGF-beta1 levels in the mouse kidney. Furthermore,
      KS370G reverses TGF-beta1-induced downregulation of E-cadherin and upregulation
      of alpha-SMA and also decreases the expression of fibronectin, collagen I and PAI
      1 and inhibits TGF-beta1-induced phosphorylation of Smad2/3. These findings show
      the beneficial effects of KS370G on renal fibrosis in vivo and in vitro with the
      possible mechanism being the inhibition of the Smad2/3 signaling pathway.

PMID- 25056458
TI  - Apoptosis and oxidative stress in neurodegenerative diseases.
AB  - Neurodegenerative disorders affect almost 30 million individuals leading to
      disability and death. These disorders are characterized by pathological changes
      in disease-specific areas of the brain and degeneration of distinct neuron
      subsets. Despite the differences in clinical manifestations and neuronal
      vulnerability, the pathological processes appear similar, suggesting common
      neurodegenerative pathways. Apoptosis seems to play a key role in the progression
      of several neurologic disorders like Alzheimer's disease, Parkinson's disease,
      Huntington's disease, and amyotrophic lateral sclerosis as demonstrated by
      studies on animal models and cell lines. On the other hand, research on human
      brains reported contradictory results. However, many dying neurons have been
      detected in brains of patients with neurodegenerative diseases, and these
      conditions are often associated with significant cell loss accompanied by typical
      morphological features of apoptosis such as chromatin condensation, DNA
      fragmentation, and activation of cysteine-proteases, caspases. Cell death and
      neurodegenerative conditions have been linked to oxidative stress and imbalance
      between generation of free radicals and antioxidant defenses. Multiple sclerosis,
      stroke, and neurodegenerative diseases have been associated with reactive oxygen
      species and nitric oxide. Here we present an overview of the involvement of
      neuronal apoptosis and oxidative stress in the most important neurodegenerative
      diseases, mainly focusing the attention on several genetic disorders, discussing
      the interaction between primary genetic abnormalities and the apoptotic pathways.

PMID- 25056459
TI  - Different subsets of Langerhans cells in human uterine tubes and uterus.
AB  - AIM: Langerhans cells (LC) are antigen-presenting cells present in tissues with
      high antigenic exposure. Their role in the upper female reproductive tract is not
      fully understood. This study aims to determine the distribution and morphology of
      LC in the normal and post-partum human uterine tubes and uterus by staining with
      the specific LC markers, CD1a and zinc iodide-osmium (ZIO), and to determine
      their association with helper and cytotoxic T cells. MATERIAL AND METHODS: Normal
      and post-partum uterine tube and uterine specimens were stained with CD1a and ZIO
      and their morphology and distribution noted. Double immune staining with CD1a-CD4
      and CD1a-CD8 in post-partum uterine tube were also done. RESULTS: It was noted
      that CD1a-positive cells were significantly fewer and smaller in diameter than
      ZIO-positive cells in the uterine tube and both types of cells were significantly
      more prevalent in post-partum tubes. Perivascular clusters of ZIO-positive cells
      were seen in the post-partum tubes. Close association of CD1a-positive cells with
      CD4- and CD8-positive T cells was noted in the post-partum uterine tube. In the
      uterus, scanty CD1a-positive cells were present in the surface and glandular
      epithelium and endometrial stroma. ZIO-positive cells were absent. CONCLUSION:
      This study suggests that CD1a-positive and ZIO-positive cells may be different
      subsets of LC that are needed for presentation of antigen to immunocompetent
      cells. Their respective functions are yet to be determined.

PMID- 25056460
TI  - Could mean platelet volume in late first trimester of pregnancy predict
      intrauterine growth restriction and pre-eclampsia?
AB  - AIM: The present study aims to determine whether mean platelet volume (MPV)
      specified in late first trimester of pregnancy can be used to predict pre
      eclampsia and intrauterine growth restriction (IUGR). METHODS: This study
      prospectively reviews 200 healthy women with 11-14-week-old pregnancies. RESULTS:
      Average pregnancy-associated plasma protein-A (PAPP-A) multiples of the median
      (MoM) value was significantly lower and MPV was significantly higher in pre
      eclamptic pregnancies (P = 0.001 for both). MPV values of 10.5 fl or more can
      predict pre-eclampsia with 66.7% sensitivity and 63.8% specificity. The
      combination of MPV of 10.5 fl or more and PAPP-A MoM of 0.33 or less can predict
      pre-eclampsia with 75% sensitivity and 70.0% specificity. MPV values of 10.5 fl
      or more can predict IUGR with 82.4% sensitivity and 60.0% specificity. The
      combination of MPV of 10.5 fl or more and PAPP-A MoM of 0.33 or less can predict
      IUGR with 85.3% sensitivity and 62.0% specificity. CONCLUSION: Increased MPV
      reflects enhanced platelet activation which may be caused by impairment in
      uteroplacental circulation. When MPV of 10.1 or more and PAPP-A MoM of 0.33 or
      less are combined as a threshold, the pregnancies that are destined to develop
      IUGR and pre-eclampsia can be predicted with considerably high sensitivity and
      specificity. The MPV and PAPP-A combination can be addressed as a useful
      biochemical tool for the prediction of IUGR and pre-eclampsia in late first
      trimester.

PMID- 25056461
TI  - Assessment of cervicovaginal vascular endothelial growth factor in predicting
      preterm delivery.
AB  - AIM: The aim of this study is to estimate the effectiveness of cervicovaginal
      vascular endothelial growth factor (VEGF) in predicting preterm delivery.
      METHODS: Cervicovaginal VEGF was measured in 30 women who presented symptoms or
      signs of threatened preterm labor and the control group of 30 healthy pregnant
      patients by enzyme-linked immunoassay. RESULTS: There was no statistically
      significant difference in cervicovaginal VEGF values between the threatened
      preterm labor group and the control group (P > 0.05). Similarly, no statistically
      significant difference was observed in terms of cervical length and
      cervicovaginal VEGF values between preterm and term-delivered groups (P > 0.05).
      Additionally, there was no correlation between cervicovaginal VEGF values and
      cervical length (P > 0.05) between the threatened preterm labor and the control
      groups. CONCLUSION: No correlation was found between cervicovaginal VEGF values
      and the preterm delivery. However, we believe that the role of VEGF in preterm
      delivery needs to be investigated further in well-designed studies with larger
      samples.

PMID- 25056462
TI  - Obstetric and neonatal outcomes of delayed interval delivery in cerclage and non
      cerclage cases: an analysis of 20 multiple pregnancies.
AB  - AIM: The aim of study is to compare maternal and fetal outcomes of pregnancies in
      which cerclage was placed following the loss of first fetus with those without
      cerclage placement in multiple pregnancies for delayed interval delivery.
      METHODS: Records of pregnancies in which the first fetus was lost between 13-26
      weeks and delayed delivery experienced for retained fetus(es), were collected
      retrospectively. A total of 20 patients including 11 twins, seven triplets and
      two quadruplets were evaluated. Cases with cervical cerclage placed after the
      first delivery were evaluated as the cerclage group (n = 11) and the cases
      without cerclage placement were evaluated as the non-cerclage group (n = 9).
      RESULTS: Median duration of delay was 22 days (range, 3-121) for both groups; 40
      days (range, 5-121) in cerclage group and 12 days (range, 3-46) in the non
      cerclage group (P = 0.003). Average birthweight of retained fetus(es) in the
      cerclage group was 850 +/- 153.6 g (mean +/- standard error [SE]) and 549.5 +/-
      149.1 g (mean +/- SE) in the non-cerclage group (P = 0.04). Delivery week of
      retained fetus(es), live birth rate, take-home baby rate and chorioamnionitis
      ratio were not different in between the groups. CONCLUSION: Cervical cerclage
      after the first delivery is associated with a longer delivery interval and higher
      birthweight of retained fetus.

PMID- 25056463
TI  - Clinical characteristics of amniotic fluid embolism: an experience of 29 years.
AB  - AIM: The aim of this study was to elucidate the clinical characteristics and risk
      factors for amniotic fluid embolism (AFE). METHODS: We performed a retrospective
      case study analysis of patients using medical records and autopsy records. The
      diagnosis of AFE was based on the presence of clinical symptoms using Clark's
      criteria and autopsy results. We analyzed patient records from a 29-year period
      in three hospitals affiliated with the Nippon Medical School in Japan. RESULTS:
      Ten diagnoses of AFE were found in the records. First, we classified AFE patients
      into two types based on the initial presenting symptoms: post-partum hemorrhage
      and cardiopulmonary collapse. Fifty percent of the patients initially presented
      with post-partum hemorrhage and disseminated intravascular coagulation. Most were
      diagnosed with post-partum hemorrhage or uterine atony at AFE onset. Similarly,
      50% presented with cardiopulmonary arrest or pulmonary arrest as initial
      symptoms, and most were diagnosed with eclampsia. Second, risk factors for AFE
      included advanced maternal age, multiparity, increased intrauterine pressure and
      disruptions of the uterine vasculature. Third, the case fatality rate was 70%.
      Fourth, squamous cells were observed in maternal central venous blood of five
      patients. CONCLUSION: AFE patients were classified into two types based on
      presenting signs and symptoms. Knowledge of the various initial symptoms of AFE
      enables a correct diagnosis.

PMID- 25056464
TI  - Assessment of sub-endometrial blood flow parameters following dydrogesterone and
      micronized vaginal progesterone administration in women with idiopathic recurrent
      miscarriage: a pilot study.
AB  - AIM: To evaluate differences in uteroplacental blood flow and pregnancy outcome
      in women with idiopathic recurrent spontaneous miscarriage (IRSM) following
      administration of micronized vaginal progesterone and oral dydrogesterone.
      METHODS: One hundred and thirty-three women (aged 23-40 years) who had had early
      miscarriages and spontaneous conception participated. Oral dydrogesterone (group
      A, n = 51) and micronized vaginal progesterone (group B, n = 50) were
      administrated for luteal support and compared. Pregnant women without history of
      recurrent miscarriage served as controls (group C, n = 32). The outcome measures
      consisted of endometrial blood flow parameters by Doppler indices and ongoing
      pregnancy rate. RESULTS: Before progesterone supplementation, resistivity index
      (RI) and pulsatility index (PI) were found to be significantly higher in groups A
      and B as compared to controls. Although statistically not significant, end
      diastolic velocity (EDV) and systolic/diastolic (S/D) ratio was found to be
      superior in controls than IRSM women. Peak systolic velocity (PSV) was comparable
      between IRSM and non-IRSM groups. Following progesterone supplementation, groups
      A and B showed a highly significant reduction in RI, PI and an increase in EDV. A
      relative increase in the value of PSV was observed in group A as compared to
      group B. There was remarkable difference in S/D in both groups. Although not
      statistically significant, group C showed reduction in RI, PI, PSV, EDV and S/D
      ratio. Pregnancy salvage rates were higher in group A (92.0%) as compared to
      group B (82.3%). CONCLUSION: Progesterone supplementation appears to lower
      vascular resistance in women with IRSM. Oral dydrogesterone appears to be equally
      effective in improving endometrial blood flow as compared with micronized
      progesterone.

PMID- 25056465
TI  - Comparison between two incision angles of mediolateral episiotomy in primiparous
      women: a randomized controlled trial.
AB  - AIM: To compare two incision angles (60 degrees  vs 40 degrees ) of mediolateral
      episiotomy in primiparous Egyptian women, regarding the incidence of anal
      sphincter injury as well as episiotomy-related pain and dyspareunia. METHODS: The
      current prospective randomized controlled trial (ClinicalTrials.gov, NCT01930721)
      was conducted at Ain Shams University Maternity Hospital. Eligible women were
      randomized into two groups: group 1 included women who had the episiotomy
      incision made at an angle of 60 degrees  to the midline; and group 2 included
      women who had the episiotomy incision made at an angle of 40 degrees  to the
      midline. Primary outcome measures were differences in short-term related pain and
      rate of third/fourth degree perineal tears. RESULTS: A total of 330 primiparous
      women were recruited. The shortest distance to the outer edge of the anal
      epithelium was significantly shorter in women of group 2 when compared to that in
      women of group 1. Out of the included 330 women, 13 (4%) had third/fourth-degree
      perineal tears (4 [2.4%] in group 1 in contrast to nine [5.5%] in group 2). This
      difference was not significant A 60 degrees -angled mediolateral episiotomy was
      associated with significantly higher rates of moderate/severe episiotomy-related
      pain post-partum. The rates of moderate/severe episiotomy-related pain and
      dyspareunia assessed 6 months post-partum were also higher among women of group
      1, when compared to group 2; the latter two differences did not reach statistical
      significance, however. CONCLUSION: When compared to the 40 degrees -angled
      mediolateral episiotomies, 60 degrees -angled ones were associated with
      significantly higher short-term-related pain. Although they were also associated
      with lower rate of third/fourth-degree perineal tears and higher rate of long
      term related pain and dyspareunia, these differences did not reach a
      statistically significant level.

PMID- 25056466
TI  - Role of postprandial bile acids in prediction of perinatal outcome in
      intrahepatic cholestasis of pregnancy.
AB  - AIM: The aim of this study was to investigate the role of fasting and
      postprandial total bile acids (fTBA, ppTBA) in prediction of adverse perinatal
      outcomes in intrahepatic cholestasis of pregnancy (ICP). MATERIAL AND METHODS: A
      total of 111 patients, 57 with ICP and 54 controls, were evaluated for preterm
      birth (PTB), meconium-stained amnion (MSA), neonatal intensive-care unit
      admission and asphyxia. We further classified the ICP group as mild and severe.
      Logistic regression was performed to evaluate the associated biochemical and
      clinical parameters with adverse perinatal outcomes. RESULTS: In the ICP group,
      PTB, asphyxia, admission to neonatal intensive-care unit, and MSA were more
      frequently observed (P = 0.001, P = 0.027, P = 0.006 and P = 0.030,
      respectively). In subgroup analysis, PTB was more frequent in severe ICP cases
      than in mild cases (P = 0.028). Fasting and ppTBA were positively correlated with
      serum aspartate aminotransferase and alanine aminotransferase levels.
      Postprandial TBA and difference between fasting and postprandial TBA levels were
      associated with asphyxia (P = 0.014 and P = 0.023, respectively). Gestational age
      at diagnosis and fTBA were associated with adverse perinatal outcomes (P = 0.001
      and P = 0.025, respectively). CONCLUSION: Postprandial TBA and difference of
      fasting and postprandial TBA are associated with asphyxia in ICP. The gestational
      age at diagnosis and fTBA are associated with adverse perinatal outcomes.

PMID- 25056467
TI  - Comparison of gadolinium-enhanced magnetic resonance imaging with ultrasound in
      evaluation of cesarean scar pregnancy.
AB  - AIM: The aim of this study was to evaluate the validity of gadolinium-enhanced
      magnetic resonance imaging (MRI) in diagnosing cesarean scar pregnancy (CSP) and
      to compare this with ultrasound results. MATERIAL AND METHODS: Forty-two
      consecutive patients underwent both gadolinium-enhanced MRI and ultrasound to
      evaluate CSP before treatment from May 2010 to September 2013. The results of
      both MRI and ultrasound were reviewed and compared to each other with diagnosis
      of CSP confirmed by pathological findings and clinical outcome. RESULTS: MRI and
      ultrasound were performed in all 42 patients, with ultrasound performed more than
      twice in 29 cases. Pathological findings confirmed CSP in all 42 patients, 41 of
      whom were diagnosed correctly using MRI, with one misdiagnosed as uterine
      fibroid. Misdiagnosis occurred in seven cases in the first ultrasound, and report
      was inconclusive in one case. However, correct and definite diagnosis was
      achieved in repeated ultrasound in seven of the eight cases. The case
      misdiagnosed as uterine fibroid using MRI was also misdiagnosed as blood clot by
      ultrasound. The specificity of MRI in diagnosing CSP was 97.6% (41/42) versus 81%
      (34/42) of the initial ultrasound (P < 0.05). No contrast-agent-related
      complications occurred in our series. CONCLUSIONS: Gadolinium-enhanced MRI is
      highly specific in the diagnosis of CSP. Ultrasound is relatively less specific
      when initially performed, but it can be repeated conveniently, with specificity
      greatly improved. Repeated ultrasound is as specific as MRI in confirming
      diagnosis of CSP.

PMID- 25056468
TI  - Prenatal differential diagnosis of complete hydatidiform mole with a twin live
      fetus and placental mesenchymal dysplasia by magnetic resonance imaging.
AB  - AIM: To assess the use of magnetic resonance imaging (MRI) for prenatal
      differentiation between complete hydatidiform mole with a twin live fetus (CHMTF)
      and placental mesenchymal dysplasia (PMD). METHODS: Three CHMTF cases and three
      PMD cases, from two institutions over a 6-year period, were retrospectively
      included in this study. Clinical findings including age, pregnancy history, serum
      hCG level, ultrasonography findings, complications of the mother, outcome of the
      fetus, and results of chromosomal study of fetus, amniotic fluid and lesion, if
      possible, were noted. MRI findings were evaluated by two radiologists with
      respect to the location of the disease (intra- or extra-fetal sac), the presence
      of multicystic component, and presence of intra- or extra-lesional hemorrhage.
      RESULTS: In all six cases, the diseases were recognized as multicystic lesions by
      ultrasonography and MRI. In two of three CHMTF cases, patients continued with the
      pregnancy, which resulted in spontaneous abortion. In one case of CHMTF, the
      patient underwent artificial abortion, after which the mole progressed into an
      invasive mole with lung metastases. All three PMD patients had live births, and
      two of the three babies had fetal growth restriction. By MRI, CHMTF was located
      within an extra-fetal sac accompanied by intra- and/or extra-lesional hemorrhage,
      while PMD was located within the placenta in the fetal sac without hemorrhage.
      CONCLUSION: MRI could provide important information about the prenatal
      differential diagnosis of CHMTF and PMD, based on the pathophysiology and
      characteristics of the diseases.

PMID- 25056469
TI  - Self-control study on reduced-dose depot versus daily administration of
      gonadotrophin-releasing hormone agonists for pituitary desensitization in in
      vitro fertilization cycles.
AB  - AIM: Our aim was to analyze the effect of reducing the dose of depot
      gonadotrophin-regulating hormone-agonist (GnRH-a) to 1.0 mg on pituitary
      desensitization and clinical outcome of in vitro fertilization and embryo
      transfer cycles. MATERIAL AND METHODS: This retrospective self-control study was
      conducted on 143 patients who underwent repeated long-protocol treatment from 1
      January 2011 to 31 May 2012 at our hospital. Of the 143 patients, 64 received
      reduced-dose depot (1.0 mg diphereline depot) GnRH-a for the first cycle and
      short-acting GnRH-a (0.05 mg diphereline) for the second cycle, while 79 patients
      received short-acting GnRH-a for the first cycle and reduced-dose depot GnRH-a
      for the second cycle. RESULTS: The serum follicle-stimulating hormone,
      luteinizing hormone and estradiol levels on the day of gonadotrophin initiation
      were significantly higher in the short-acting group compared with the long-acting
      group. Both number of days of gonadotrophin stimulation and gonadotrophin doses
      were significantly higher in the short-acting group. On the day of human
      chorionic gonadotrophin administration, the serum estradiol level was
      significantly higher while the progesterone level was significantly lower in the
      short-acting group. There were no significant differences with regard to the
      number of retrieved oocytes, fertilization rate, number of transferred embryos,
      clinical pregnancy rate, implantation rate, and early pregnancy loss rate between
      the two groups. However, the oocyte maturation rate was significantly higher in
      the long-acting group. CONCLUSION: Reduced-dose depot GnRH-a can be successfully
      used for pituitary desensitization in in vitro fertilization and embryo transfer.
      Deeper downregulation with reduced-dose depot GnRH-a indicates that the optimal
      dose of GnRH-a warrants future study.

PMID- 25056470
TI  - Novel reversible permanent contraception: an animal experiment of embedding
      contraceptive surgery in the fimbriated extremity of the fallopian.
AB  - AIM: According to female pelvic anatomical characteristics, we designed a novel
      reversible permanent contraception: embedding contraceptive surgery in the
      fimbriated extremity of the fallopian. This study involves embedding the oviduct
      of New Zealand rabbits into the peritoneum, and assesses contraceptive effect,
      morphological changes and recoverability. METHODS: Thirty New Zealand rabbits
      were divided into three groups: embedding in the fimbriated extremity of the
      fallopian group (A group); polyethylene film in the fimbriated extremity of the
      fallopian group (B group); and control (C group). Surgery was performed in each
      group, respectively. Contraceptive efficacy, morphological changes and
      recoverability were noted. RESULTS: As for contraceptive effect, mating
      experiences were successful. After 3 months, there were no pregnant rabbits in
      group A and B, while in group C all samples were pregnant. Regarding
      recoverability, after belly operation, 10 rabbits in group A showed dropsy in the
      bilateral oviducts. Tissue adhesion could be found in the fimbriated extremity of
      the fallopian with a large range of damage. All samples in group B also had
      dropsy, but only two of them had unilateral slight adhesions in the fimbriated
      extremity of the fallopian, while others had no pathological changes. After being
      released from the oviduct embedding, five rabbits in group A became pregnant and
      nine in group B. CONCLUSION: Embedding contraceptive surgery in the fimbriated
      extremity of the fallopian after being covered by polyethylene film is reliable
      and safe. Releasing the embedding may cause minor injury. Although there is a
      problem of hydrosalpinx, the pregnancy rate is high.

PMID- 25056471
TI  - Efficacy of kidney-tonifying traditional Chinese medicine prescriptions in
      hypoplastic uterus treatment: a systematic review and meta-analysis.
AB  - AIM: To review and evaluate the efficacy of kidney-tonifying traditional Chinese
      medicine prescriptions (KT-TCMP) in hypoplastic uterus (HU) treatment. METHODS:
      We searched MEDLINE, the Cochrane Library, CNKI (China National Knowledge
      Infrastructure), WANFANG and VIP databases until 14 December 2013 independently
      with two investigators. Randomized controlled trials (RCT) involving KT-TCMP as a
      combined or monotherapy in the treatment of HU were reviewed and analyzed. Meta
      analysis was performed by Review Manager (version 5.2). RESULTS: Nine RCT of 1745
      patients were eligible for this review and meta-analysis, of which eight RCT
      described the primary outcome of clinical efficacy and three RCT drew the
      secondary outcome of uterine size. Meta-analyzed 'recovery' clinical efficacy of
      KT-TCMP in seven RCT was conducted which considered diethylstilbestrol therapy
      alone as control, as well as three RCT that meta-analyzed the effect of KT-TCMP
      on uterine diameter enlargement. As a result, KT-TCMP therapy had a significantly
      improved difference in increasing 'recovery' clinical efficacy (risk ratio, 2.34;
      95% confidence interval [CI], 1.90-2.89) and enlarging the uterine diameter
      (standardized mean difference, 1.62; 95% CI, 1.39-1.84). One study reported
      adverse reactions as an important outcome and found it was safe during KT-TCMP
      therapy. CONCLUSION: The therapy of applying KT-TCMP as a combined or monotherapy
      in the treatment of HU may be more efficacious. However, these RCT were of
      moderate methodological quality and small sample size; thus, the results should
      be confirmed with more rigorously controlled further studies.

PMID- 25056472
TI  - Expression of glucose transporter protein 1 and p63 in serous ovarian tumor.
AB  - AIM: It has been shown that glycolytic metabolism is increased in malignant
      cells. Cancer cell growth is an energy-related process supported by an increased
      glucose metabolism. In addition, p63, a known homolog of p53, is expressed
      predominantly in basal cell and squamous cell carcinomas. The purpose of this
      study was to evaluate the expression of glucose transporter protein 1 (GLUT1) and
      p63 in patients with serous ovarian tumor (benign, borderline and malignant) and
      study their close relationship with the malignant transformation of serous
      ovarian tumors. METHODS: Two hundred formalin-fixed, paraffin-embedded sections
      were immunostained with rabbit anti-GLUT1 polyclonal antibody and mouse anti-p63
      monoclonal antibody using the streptavidin-biotin method. The samples were as
      follows: 40 normal ovarian tissues, 40 serous cystadenomas, 40 borderline serous
      cystadenomas and 80 serous cystadenocarcinomas were stained. RESULT: Normal
      ovarian tissues showed completely negative staining for GLUT1 and p63. However,
      from benign serious cystadenomas, borderline cystadenomas to cystadenocarcinomas,
      the expression of GLUT1 and p63 grew stronger (P < 0.05). Moreover, the intensity
      staining of GLUT1 maintained a significant association with the expression of p63
      (P < 0.05). In chi2-test analysis, expression of borderline cystadenomas and
      cystadenocarcinomas, intraperitoneal implants, ascites, lymph node status and
      International Federation of Gynecology and Obstetrics (FIGO) stage and GLUT1
      expression levels have an appalling significance (P < 0.05), while FIGO stage,
      intraperitoneal implants and lymph node status except patient age and ascites
      have a statistical significance with the expression of p63 levels (P < 0.05).
      CONCLUSION: Our findings show a progressive increase in the expression of GLUT1
      and p63 from the benign serous cystadenomas, borderline cystadenomas to
      cystadenocarcinomas. Overexpression of GLUT1 and p63 are associated with the
      histology FIGO stage and metastasis of the tumors. These data suggested that the
      expression of GLUT1 and p63 may be closely related to the malignant
      transformation of serous ovarian tumors. However, the relative importance of
      GLUT1 and p63 in ovarian serous tumor development and tumorigenesis remains
      mostly unclear and awaits further investigation.

PMID- 25056473
TI  - Prediction of histological types of endometrial cancer by endometrial cytology.
AB  - AIM: Few studies have examined the accuracy of preoperative endometrial cytology
      in diagnosing low- and high-risk histology in women with endometrial cancer (EC).
      This single-institutional retrospective study compared the accuracy of
      endometrial cytology and biopsy in preoperatively predicting low-risk and high
      risk histology of EC. METHODS: Between January 2006 and March 2013, 198 women
      with EC were examined by endometrial cytology, endometrial biopsy and
      hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110
      had endometrial cytology samples available to compare with endometrial biopsy,
      and were enrolled in our study (mean age +/- standard deviation: 59.57 +/- 10.32
      years). Single-use plastic endometrial suction curettes were used in 12 of the
      110 cases and thin metallic curettes for the rest. RESULTS: For type 2 EC, which
      includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology,
      biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology
      was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely
      diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14
      cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior
      to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using
      biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002).
      CONCLUSION: Although preoperative prediction of serous carcinoma was difficult,
      endometrial cytology had a higher evaluable rate for EC types. Endometrial
      cytology may complement endometrial biopsy in preoperative women with EC.

PMID- 25056474
TI  - Extracorporeal membrane oxygenation saved a mother and her son from fulminant
      peripartum cardiomyopathy.
AB  - A 34-year-old full-term pregnant woman presented with abruptly aggravating
      dyspnea. A chest X-ray showed pulmonary edema, and an echocardiogram revealed a
      left ventricular ejection fraction of 39%. Despite conventional medical treatment
      for acute heart failure and mechanical ventilation, hypoxia and metabolic
      acidosis were aggravated, and the fetal heart rate decreased to 90 b.p.m.,
      suggestive of fetal distress. We decided to initiate extracorporeal membrane
      oxygenation (ECMO) and perform a cesarean section. The infant was successfully
      delivered without hypoxic brain damage. The patient was weaned from ECMO 6 days
      after delivery and was extubated 1 day after discontinuation of ECMO. Left
      ventricular systolic function had completely recovered at this time. This is the
      first report of a patient with peripartum cardiomyopathy who had a successful
      delivery with the support of ECMO, demonstrating that ECMO can serve as a rescue
      therapy, not only treating peripartum cardiomyopathy but also permitting a safe
      delivery. 

PMID- 25056475
TI  - Concentrated ascites re-infusion therapy for pseudo-Meigs' syndrome complicated
      by massive ascites in large pedunculated uterine leiomyoma.
AB  - Pseudo-Meigs' syndrome accompanied by massive ascites in uterine leiomyoma is
      rare. We encountered a rare case of a 37-year-old, nulliparous woman with a lower
      abdominal tumor and severe abdominal distention due to massive ascites. Serum
      cancer antigen 125 and vascular endothelial growth factor levels were elevated to
      1007.9 U/mL and 103 pg/mL, respectively. She was tentatively diagnosed with
      ovarian cancer. Emergency concentrated ascites re-infusion therapy was performed
      to improve dyspnea, abdominal pain, and her preoperative respiratory condition.
      Concentrated ascites re-infusion therapy eliminated dyspnea and abdominal
      discomfort without decreasing serum albumin levels. The patient underwent
      laparotomy, which revealed a fist-sized pedunculated uterine leiomyoma arising
      from the right uterine fundus. Myomectomy was performed. Pseudo-Meigs' syndrome
      mimics advanced ovarian cancer due to massive ascites and markedly elevated serum
      cancer antigen 125 and vascular endothelial growth factor levels. Concentrated
      ascites re-infusion therapy was effective in improving the subjective symptoms of
      pseudo-Meigs' syndrome and the patient's preoperative condition. 

PMID- 25056476
TI  - Coring-type laparoscopic resection of a cavitated non-communicating rudimentary
      horn under hysteroscopic assistance.
AB  - Non-communicating accessory uterine horns with an endometrial cavity are the most
      common and clinically significant unicornuate subtype of Mullerian duct
      abnormality. They are generally associated with symptoms of dysmenorrhea,
      dyspareunia, infertility, endometriosis, adhesions, and life-threatening cornual
      pregnancy. Treatment options include surgical resection of the rudimentary horn,
      hysteroscopic recanalization, and endometrial ablation. Currently, laparoscopic
      resection is the recommended treatment choice. Dissection of the rudimentary horn
      from the unicornuate uterus is the most challenging part of this procedure and
      may compromise the remaining unicornuate uterus wall. Here we describe a case of
      laparoscopic coring-type resection of a non-communicating functional rudimentary
      horn firmly attached to the unicornuate uterus, by using hysteroscopic
      assistance. The use of hysteroscopy, adjunct to laparoscopy, facilitates the
      coring-type resection and may strengthen the remaining myometrial scar. 

PMID- 25056477
TI  - Platelet values measurement. What we know about it?

PMID- 25056478
TI  - Uterine fundal pressure: is it really a culprit of poor maternal and neonatal
      outcome?

PMID- 25056479
TI  - Towards molecular construction platforms: synthesis of a metallotricyclic spirane
      based on bis(2,2':6',2"-terpyridine)RuII connectivity.
AB  - The design and construction of the first multicomponent stepwise assembly of a
      <tpy-Ru(II) -tpy>-based (tpy=terpyridine), three-dimensional, propeller-shaped
      trismacrocycle, 8, are reported. Key steps in the synthesis involve the
      preparation of a hexaterpyridinyl triptycene and its reaction with dimeric, 60
      degrees -directional, bisterpyridine-Ru(II) building blocks. Characterization
      includes ESI- and ESI-TWIM-MS and TEM, along with 1D and 2D (1) H NMR
      spectroscopy. 

PMID- 25056481
TI  - Reference-free SNP detection: dealing with the data deluge.
AB  - Reference-free SNP detection, that is identifying SNPs between samples directly
      from comparison of primary sequencing data with other primary sequencing data and
      not to a pre-assembled reference genome is an emergent and potentially disruptive
      technology that is beginning to open up new vistas in variant identification that
      reveals new applications in non-model organisms and metagenomics. The modern,
      efficient data structures these tools use enables researchers with a reference
      sequence to sample many more individuals with lower computing storage and
      processing overhead. In this article we will discuss the technologies and tools
      implementing reference-free SNP detection and the potential impact on studies of
      genetic variation in model and non-model organisms, metagenomics and personal
      genomics and medicine.

PMID- 25056480
TI  - A novel elicitor identified from Magnaporthe oryzae triggers defense responses in
      tobacco and rice.
AB  - KEY MESSAGE: Our studies indicate a potential important elicitor candidate which
      can aid in the fight against a worldwide disease, rice blast. In this study, we
      report the purification, identification, characterization, and gene cloning of a
      novel hypersensitive response-inducing protein elicitor (MoHrip2) secreted from
      an important pathogenic fungus, Magnaporthe oryzae. The protein fraction was
      isolated from the culture filtrate of M. oryzae and identified by de novo
      sequencing. The elicitor-encoding gene mohrip2 was cloned following sequence
      comparison and PCR amplification. This 459-bp gene encodes a 152-residue
      polypeptide that contains an 18-residue signal peptide and exhibits a pI of 4.72
      and an apparent molecular mass of 16 kDa. The hypothetical protein, MoHrip2, was
      expressed in Escherichia coli, and both the recombinant and the endogenous
      protein caused necrotic lesions in tobacco leaves. In addition to phenolic
      compound deposition and alkalization of the extracellular medium, MoHrip2 also
      induced hydrogen peroxide production and nitric oxide accumulation in tobacco
      cells. Moreover, rice seedlings treated with MoHrip2 exhibited pronounced
      resistance to M. oryzae compared with control seedlings.

PMID- 25056482
TI  - A new tetracyclic lactam building block for thick, broad-bandgap photovoltaics.
AB  - A new tetracyclic lactam building block for polymer semiconductors is reported
      that was designed to combine the many favorable properties that larger fused
      and/or amide-containing building blocks can induce, including improved solid
      state packing, high charge carrier mobility, and improved charge separation.
      Copolymerization with thiophene resulted in a semicrystalline conjugated polymer,
      PTNT, with a broad bandgap of 2.2 eV. Grazing incidence wide-angle X-ray
      scattering of PTNT thin films revealed a strong tendency for face-on pi-stacking
      of the polymer backbone, which was retained in PTNT:fullerene blends.
      Corresponding solar cells featured a high open-circuit voltage of 0.9 V, a fill
      factor around 0.6, and a power conversion efficiency as high as 5% for >200 nm
      thick active layers, regardless of variations in blend stoichiometry and
      nanostructure. Moreover, efficiencies of >4% could be retained when thick active
      layers of ~400 nm were employed. Overall, these values are the highest reported
      for a conjugated polymer with such a broad bandgap and are unprecedented in
      materials for tandem and particularly ternary blend photovoltaics. Hence, the
      newly developed tetracyclic lactam unit has significant potential as a conjugated
      building block in future organic electronic materials. 

PMID- 25056484
TI  - Male facial attractiveness and masculinity may provide sex- and culture
      independent cues to semen quality.
AB  - Phenotype-linked fertility hypothesis (PLFH) predicts that male secondary sexual
      traits reveal honest information about male fertilization ability. However, PLFH
      has rarely been studied in humans. The aim of the present study was to test PLFH
      in humans and to investigate whether potential ability to select fertile partners
      is independent of sex or cultural background. We found that on the contrary to
      the hypothesis, facial masculinity was negatively associated with semen quality.
      As increased levels of testosterone have been demonstrated to impair sperm
      production, this finding may indicate a trade-off between investments in
      secondary sexual signalling (i.e. facial masculinity) and fertility or status
      dependent differences in investments in semen quality. In both sexes and
      nationalities (Spanish and Colombian), ranked male facial attractiveness
      predicted male semen quality. However, Spanish males and females estimated facial
      images generally more attractive (gave higher ranks) than Colombian raters, and
      in both nationalities, males gave higher ranks than females. This suggests that
      male facial cues may provide culture- and sex-independent information about male
      fertility. However, our results also indicate that humans may be more sensitive
      to facial attractiveness cues within their own populations and also that males
      may generally overestimate the attractiveness of other men to females. 

PMID- 25056485
TI  - Can the risk of obstetric anal sphincter injuries (OASIs) be predicted using a
      risk-scoring system?
AB  - BACKGROUND: Perineal trauma involving the anal sphincter is an important
      complication of vaginal delivery. Prediction of anal sphincter injuries may
      improve the prevention of anal sphincter injuries. Our aim was to construct a
      risk scoring model to assist in both prediction and prevention of Obstetric Anal
      Sphincter Injuries (OASIs). We carried out an analysis of factors involved with
      OASIs, and tested the constructed model on new patient data. METHODS: Data on all
      vaginal deliveries over a 5 year period (2004-2008) was obtained from the
      electronic maternity record system of one institution in the UK. All risk factors
      were analysed using logistic regression analysis. Odds ratios for independent
      variables were then used to construct a risk scoring algorithm. This algorithm
      was then tested on subsequent vaginal deliveries from the same institution to
      predict the incidence of OASIs. RESULTS: Data on 16,920 births were analysed.
      OASIs occurred in 616 (3.6%) of all vaginal deliveries between 2004 and 2008.
      Significant (p < 0.05) variables that increased the risk of OASIs on multivariate
      analysis were: African-Caribbean descent, water immersion in labour, water birth,
      ventouse delivery, forceps delivery. The following variables remained
      independently significant in decreasing the risk of OASIs: South Asian descent,
      vaginal multiparity, current smoker, home delivery. The subsequent odds ratios
      were then used to construct a risk-scoring algorithm that was tested on a
      separate cohort of patients, showing a sensitivity of 52.7% and specificity of
      71.1%. CONCLUSIONS: We have confirmed known risk factors previously associated
      with OASIs, namely parity, birth weight and use of instrumentation during
      delivery. We have also identified several previously unknown factors, namely
      smoking status, ethnicity and water immersion. This paper identifies a risk
      scoring system that fulfils the criteria of a reasonable predictor of the risk of
      OASIs. This supersedes current practice where no screening is implemented other
      than examination at the time of delivery by a single examiner. Further
      prospective studies are required to assess the clinical impact of this scoring
      system on the identification and prevention of third degree tears.

PMID- 25056486
TI  - Photo- and pH-tunable multicolor fluorescent nanoparticle-based spiropyran- and
      BODIPY-conjugated polymer with graphene oxide.
AB  - We report a stimuli-responsive fluorescent nanomaterial, based on graphene oxide
      coupled with a polymer conjugated with photochromic spiropyran (SP) dye and
      hydrophobic boron dipyrromethane (BODIPY) dye, for application in triggered
      target multicolor bioimaging. Graphene oxide (GO) was reduced by catechol
      conjugated polymers under mildly alkaline conditions, which enabled to formation
      of functionalized multicolor graphene nanoparticles that can be induced by
      irradiation with UV light and by changing the pH from acidic to neutral.
      Investigation of these nanoparticles by using AFM, fluorescence emission, and in
      vitro cell and in vivo imaging revealed that they show different tunable colors
      in bioimaging applications and, more specifically, in cancer-cell detection. The
      stability, biocompatibility, and quenching efficacy of this nanocomposite open a
      different perspective for cell imaging in different independent colors,
      sequentially and simultaneously. 

PMID- 25056487
TI  - Traditional uses of plants in a rural community of Mozambique and possible links
      with Miombo degradation and harvesting sustainability.
AB  - BACKGROUND: Miombo woodlands play an important role in the livelihood of people
      living in sub-equatorial African countries, contributing to satisfy basic human
      needs such as food, medicine, fuelwood and building materials. However, over
      exploitation of plant resources and unsustainable harvest practices can
      potentially degrade forests. The aim of this study was to document the use of
      Miombo plant products, other than medicinal plants, in local communities, within
      a wider framework in which we discussed possible links between traditional uses
      and conservation status of the used species and of the whole Miombo environment.
      METHODS: Fieldwork took place in four communities of Muda-Serracao, central
      Mozambique. We conducted semi-structured interviews with 52 informants about
      their knowledge, use and harvesting practices of useful plants. A survey on local
      Miombo vegetation was also carried out in order to assess abundance and
      distribution of useful woody plants cited in the interviews in areas exposed to
      different exploitation rates. A Conservation Priority index was also applied to
      rank conservation values of each used woody species. RESULTS: Ninety-eight plants
      cited by the informants were botanically identified. The most relevant general
      category was represented by food plants (45 species), followed by handicraft
      plants (38 species) and domestic plants (37 species). Among the 54 woody species
      observed in vegetation plots, 52% were cited as useful in the interviews. Twenty
      six woody species found in 'natural' Miombo areas were not found in 'degraded'
      ones: of these, 46% were cited in the interviews (58% in the food category, 50%
      in the handicraft category, 25% in the domestic category and 8% in the fishing
      category). Results of conservation ranking showed that 7 woody species deserve
      conservation priority in the investigated area. CONCLUSIONS: This study shows
      that the communities investigated rely heavily on local forest products for their
      daily subsistence requirements in food, firewood/charcoal and building materials.
      However, over-exploitation and destructive collection seem to threaten the
      survival of some of the woody species used. A sustainable approach including the
      involvement of local communities in the management of woody species is
      recommended.

PMID- 25056488
TI  - A multidisciplinary network for the care of abnormal fatigue and chronic fatigue
      syndrome in the provinces of East and West Flanders in Belgium.
AB  - The organization of care for patients with the chronic fatigue syndrome (CFS) in
      tertiary care referral centres from 2002 onwards, was negatively evaluated by the
      Belgian Health Care Knowledge Centre on the endpoint of socio-professional
      reintegration. Subsequently, the federal health authorities asked for the
      elaboration of a new and innovative model of stepped care, aiming at improved
      integration of diagnosis and treatment into primary care and between levels of
      health care for patients with CFS. The reference centre of the University
      Hospital Ghent took the initiative of recruiting partners in the Belgian
      provinces of East and West Flanders to guarantee the care for patients with
      medically unexplained symptoms, in particular abnormal fatigue and CFS. A new and
      innovative care model, in which general practitioners play a central role,
      emphasizes the importance of early recognition of the patient 'at risk', correct
      diagnosis and timely referral. Early detection and intervention is essential in
      order to avoid or minimize illness progression towards chronicity, to safeguard
      opportunities for significant health improvement as well as to enhance successful
      socio-professional reintegration. This approach covers both the large sample of
      patients developing somatic complaints without obvious disease in an early phase
      as well as the more limited group of patients with chronic illness, including
      CFS. Cognitive behavioural therapy and graded exposure/exercise therapy are the
      evidence based main components of therapy in the latter. A biopsychosocial model
      underlies the proposed path of care. 

PMID- 25056489
TI  - Tuberculous mastitis presenting as a lump: a mimicking disease in a pregnant
      woman case report and review of literature.
AB  - Tuberculosis (TB) of the breast is a rare entity, and can be confused with many
      other breast disorders, like mamma carcinoma or inflammatory breast cancer. When
      finding granulomatous mastitis (GM) on histology, it is important to make a
      differential diagnosis and seek actively for clues on the presence of
      tuberculosis, sarcoidosis, Wegener's granulomatosis, or idiopathic granulomatous
      mastitis, since treatment strategies differ and maltreatment has major
      implications on morbidity and mortality. An extensive clinical evaluation,
      laboratory work up, and imaging will lead in most cases to the right diagnosis.
      Anti-tuberculous therapy is the core treatment for breast TB, and surgery is
      indicated for extensive or persistent residual disease. Here we present a case of
      tuberculous mastitis and a review of literature on GM. 

PMID- 25056490
TI  - Massive pericardial effusion and rhabdomyolysis secondary to untreated severe
      hypothyroidism: the first report.
AB  - Hypothyroidism is an endocrine disease with various clinical manifestations. It
      is a rare cause for rhabdomyolysis and massive pericardial effusion. We describe
      a case of severe hypothyroidism secondary to autoimmune hashimoto thyroiditis
      with massive pericardial effusion and rhabdomyolysis. Improvement of mentioned
      complications after hypothyroidism treatment and rule out of other possible
      causes are supportive clues that hypothyroidism is the main cause of patient's
      rare presentation. With the best of our knowledge, it is the first report of
      rhabdomyolysis and massive pericardial effusion coincidence in a patient of adult
      population with primary uncontrolled hypothyroidism for years. 

PMID- 25056491
TI  - Prospective non-interventional multicentre observational trial of first-line anti
      cancer treatment in patients with metastatic renal cell cancer in Belgium.
AB  - OBJECTIVES: Renal cell carcinoma (RCC) accounts for 2.4% of all new cancers in
      Belgium. Over the past decade, the armamentarium for systemic therapy of
      metastatic RCC (mRCC) has undergone important changes with implementation of
      targeted therapies directed against pathways involved in the pathogenesis of RCC.
      We describe first-line treatment choice of a group of patients in 9 Belgian
      oncology centres between October 2009 and November 2012. METHODS: A clinical
      report form was established to assess patient characteristics, Karnofsky
      performance score, Memorial Sloan-Kettering Cancer Center risk criteria (MSKCC)
      and first-line therapy of mRCC patients. Choice of therapy and starting dose was
      analyzed before and after reimbursement of pazopanib in Belgium. RESULTS: Ninety
      six patients were eligible for the study. Non-smokers accounted for 53% of the
      patients. Seventy-three per cent of the patients had 0 or 1 MSKCC criteria in the
      group of patients that started treatment more than 1 year after initial
      diagnosis. In the group of patients that started therapy less than 1 year after
      diagnosis, 85% had 2 or more MSKCC criteria. This difference was statistically
      significant (P<0.0001). Overall distribution of the first-line therapies
      consisted of 43% sunitinib, 33% pazopanib, 14% temsirolimus, 7% everolimus and 3%
      sorafenib. Seventeen (18%) out of 96 patients started at a reduced dose level.
      CONCLUSION: This report shows that the guidelines for the start of first-line
      treatment in mRCC in 9 centres in Belgium were applied most of the time: a
      tyrosine kinase inhibitor was the first treatment choice for most patients while
      temsirolimus was an option for poor prognosis patients. In the majority of
      patients standard dose levels were initiated, although in some patients
      adaptation of dosage/treatment schedule was recorded.

PMID- 25056492
TI  - Retrospective analysis of a suburban out-of-hours clinic in Belgium.
AB  - INTRODUCTION: In many countries, out-of-hours medical care is under scrutiny. The
      aim of this article is to study the activities recorded by the first out-of-hours
      clinic that has been opened, as a pilot study, in two Walloon communes. MATERIAL
      AND METHOD: A retrospective analysis of anonymized data was conducted for 2009.
      Coding of diagnoses was conducted using the International Classification of
      Primary Care (ICPC-2). RESULTS: A total of 3949 contacts were recorded in 2009
      with the out-of-hours clinic, 3294 related to inhabitants of the two communes
      covered, which was equivalent to 13% of the total population in question.
      Compared to 7.2% of contacts between midnight and 8 a.m., 82.9% of contacts took
      place between 8 a.m. and 9 p.m., and 91.6% of contacts were handled locally, with
      only 8.4% resulting in hospitalization. In addition, 52% of contacts were with
      patients aged between 25 and 65; 29.9% of contacts were with paediatric patients
      (<15 years). Patients over the age of 65 made up 18% of contacts. The most common
      pathologies were respiratory (R). Analysis of flu diagnoses identified two
      epidemic peaks. DISCUSSION: The suburban out-of-hours clinic studied fulfilled an
      important role in managing the demand for health care. The large majority of
      health problems were resolved locally, and the inhabitants did not need to go to
      hospital. Appointments between midnight and 8 a.m. were in the minority, which
      points towards adjusting the organization of the out-of-hours service during the
      night. The geriatric population is not highly over-represented contrary to what
      might be expected considering its largest number of pathologies. The on-call
      doctor's skills profile should take account of the populations and morbidities
      encountered. Out-of-hours clinics could possibly play a sentinel role in terms of
      flu epidemics. CONCLUSION: This study describes a pilot suburban out-of-hours
      clinic which met three of recommendations set by the KCE in its report on out-of
      hours care in general medicine: the organization of an out-of-hours clinic with
      logistical support, the use of a single telephone number and merging out-of-hours
      areas. While debate exists on the management of out-of-hours care, this study
      provides evidence on the role of the physician during these hours.

PMID- 25056493
TI  - Management of the neonate at risk for early-onset Group B streptococcal disease
      (GBS EOD): new paediatric guidelines in Belgium.
AB  - Despite group B streptococcal (GBS) screening in late pregnancy and intrapartum
      antimicrobial prophylaxis, early-onset sepsis in neonates remains a common source
      of neonatal morbidity and mortality especially in preterm neonates. The
      identification of neonates with early-onset sepsis is usually based on perinatal
      risk factors. Clinical signs are aspecific and laboratory tests are not
      sensitive. Therefore, many clinicians will overtreat at-risk infants.
      Inappropriate treatment with antibiotics increases the risk for late-onset
      sepsis, necrotizing enterocolitis, mortality, and prolongs hospitalisation and
      costs. In 2003, the Belgian Health Council published guidelines for the
      prevention of perinatal GBS infections. This report presents the Belgian
      paediatric management guidelines, which have been endorsed by the Belgian and
      Flemish societies of neonatology and paediatrics. The most imported changes in
      the 2014 guidelines are the following: recommendations for a lumbar puncture;
      clarification of normal spinal fluid parameters and blood neutrophil indices
      corrected for gestation age; specific timing for diagnostic testing after birth;
      no indication for diagnostic testing in asymptomatic newborns unless additional
      risk factors; a revised algorithm for management of neonates according to
      maternal and neonatal risk factors; and premature infants described as those
      below 35 weeks instead of 37 weeks. The guidelines were made on the basis of the
      best evidence and on expert opinion when inadequate evidence exists. 

PMID- 25056494
TI  - [Specific aspects of anesthesiological management of laser surgery in
      otorhinolaryngology].
AB  - Transoral laser surgery has become a standard procedure in the treatment of
      benign and malignant neoplasms of the upper aerodigestive tract. As the laser
      cuts and coagulates simultaneously, intraoperative bleeding is reduced, thus
      improving visualization of the operative field. However, the specific risks for
      patients and personnel that are associated with this technique necessitate strict
      compliance with safety regulations and precautions. The safe anesthesiological
      and surgical management of such procedures requires explicit knowledge of the
      risks inherent to laser use, as well as close communication between surgeon and
      anesthesiologist throughout all operative and perioperative procedures. Although
      potentially fatal complications are rare, surgeon and anesthesiologist need to be
      aware of the dangers at all times and have exact knowledge of emergency measures.
      The use of suitable laser-resistant endotracheal tubes, total intravenous
      anesthesia and an optimized breathing gas mixture can contribute to minimize the
      occurrence of complications in otorhinolaryngology laser surgery. 

PMID- 25056495
TI  - Efficient knockout of transplanted green fluorescent protein gene in medaka using
      TALENs.
AB  - Transcription activator-like effector nucleases (TALENs) are used for gene
      knockout and genome-editing studies in zebrafish, and these techniques have the
      potential to be applied to other fish species. Here, we show that TALENs can
      directly knock out a green fluorescent protein (GFP) transgene in medaka by
      affecting translation and synthesis of the GFP. We constructed a transgenic
      plasmid (pGFP-RFP) carrying the GFP and red fluorescent protein (RFP) genes, and
      used a modified TALEN method to assemble a pair of TALENs for the core
      chromophore Y66 region of GFP. Embryo toxicity of TALEN messenger RNA (mRNA) was
      far lower than the linearized plasmid; meanwhile, 76.3 % embryos, green
      fluorescence of embryos decreased significantly after co-injection of TALEN mRNA
      and the linearized plasmid, but red fluorescence showed no significant change.
      Real-time quantitative polymerase chain reaction and sequencing results showed
      that nearly 100 % mutated GFP position was disrupted at the Y66 region of GFP in
      the co-injected medaka embryos, caused by TALENs. This led to random insertion
      deletion of nucleotides, which affected the translation of GFP and disrupted GFP
      synthesis. This provides new experimental evidence for designing TALEN sites in
      genes for which only key functional domains are known. Our results show that a
      modified TALEN method can efficiently and specifically mediate a transgene
      knockout in medaka. This report may promote the application of TALENs in gene
      editing studies of fish species other than zebrafish. 

PMID- 25056497
TI  - Editorial Comment to Nationwide survey of urogenital tuberculosis in Japan.

PMID- 25056496
TI  - Prediction of pharmacokinetics and drug-drug interactions when hepatic
      transporters are involved.
AB  - Hepatobiliary transport mechanisms have been identified to play a significant
      role in determining the systemic clearance for a number of widely prescribed
      drugs and an increasing number of new molecular entities (NMEs). While
      determining the pharmacokinetics, drug transporters also regulate the target
      tissue exposure and play a key role in regulating the pharmacological and/or
      toxicological responses. Consequently, it is of great relevance in drug discovery
      and development to assess hepatic transporter activity in regard to
      pharmacokinetic and dose predictions and to evaluate pharmacokinetic variability
      associated with drug-drug interactions (DDIs) and genetic variants. Mechanistic
      predictions utilizing physiological-based pharmacokinetic modeling are
      increasingly used to evaluate transporter contribution and delineate the
      transporter-enzyme interplay on the basis of hypothesis-driven functional in
      vitro findings. Significant strides were made in the development of in vitro
      techniques to facilitate characterization of hepatobiliary transport. However,
      challenges exist in the quantitative in vitro-in vivo extrapolation of
      transporter kinetics due to the lack of information on absolute abundance of the
      transporter in both in vitro and in vivo situations, and/or differential function
      in the holistic in vitro reagents such as suspended and plated hepatocytes
      systems, and lack of complete mechanistic understanding of liver model structure.
      On the other hand, models to predict transporter-mediated DDIs range from basic
      models to mechanistic static and dynamic models. While basic models provide
      conservative estimates and are useful upfront in avoiding false negative
      predictions, mechanistic models integrate multiple victim and perpetrator drugs
      parameters and are expected to provide quantitative predictions. The aim of this
      paper is to review the current state of the model-based approaches to predict
      clinical pharmacokinetics and DDIs of drugs or NMEs that are substrates of
      hepatic transporters. 

PMID- 25056498
TI  - UK research funding bodies' views towards public participation in health-related
      research decisions: an exploratory study.
AB  - BACKGROUND: A challenge facing science is how to renew and improve its
      relationship with society. One potential solution is to ensure that the public
      are more involved in the scientific process from the inception of research plans
      to scientific dissemination strategies. However, to date, little is known about
      how research funding bodies view public participation in research funding
      decisions, and how they involve the public into their strategies and practices.
      This paper provides insights into how key representatives working in the UK non
      commercial research funding sector perceive public participation in health
      related research funding decisions and the possible implications of these.
      METHODS: We conducted qualitative semi-structured interviews with 30 key
      stakeholders from 10 UK non-commercial research funding bodies that either
      partially or exclusively fund health-related research. The findings were written
      up in thematic narrative form. RESULTS: The different disciplines that encompass
      health research, and their differing frames of 'science and society', were found
      to influence how research funding bodies viewed and implemented public
      participation in research funding decisions. Relevant subsets of the public were
      more likely to be involved in research funding decisions than lay public, which
      could be linked to underlying technocratic rationales. Concerns about public
      participation stemmed from the highly professionalised scientific environment
      that the public were exposed to. Additionally, from a more positivist frame,
      concerns arose regarding subjective views and values held by the public that may
      damage the integrity of science. CONCLUSION: Underlying assumptions of
      technocracy largely appear to be driving PP/PE within the research grant review
      process, even in funding bodies that have overtly democratic ideals. Some
      conceptions of technocracy were more inclusive than others, welcoming different
      types of expertise such as patient or research-user experiences and knowledge,
      while others suggested taking a narrower and more positivist view of expertise as
      techno-scientific expertise. For research to have its maximum impact when
      translated into healthcare, health policies and health technologies, there needs
      to be sensitivity towards multiple frames of knowledge, expertise and underlying
      values that exist across science and society.

PMID- 25056499
TI  - Increased phosphorylation of Ca(2+) handling proteins as a proarrhythmic
      mechanism in myocarditis.
AB  - BACKGROUND: Because fatal arrhythmia is an important cause of death in patients
      with myocarditis, we investigated the proarrhythmic mechanisms of experimental
      autoimmune myocarditis. METHODS AND RESULTS: Myocarditis was induced by injection
      of 2 mg porcine cardiac myosin into the footpads of adult Lewis rats on days 1
      and 8 (Myo, n=15) and the results compared with Control rats (Control, n=15). In
      an additional 15 rats, 6 mg/kg prednisolone was injected into the gluteus muscle
      before the injection of porcine cardiac myosin on days 1 and 8 (MyoS, n=15).
      Hearts with myocarditis had longer action potential duration (APD), slower
      conduction velocity (CV; P<0.01 vs. Control), higher CV heterogeneity, greater
      fibrosis, higher levels of immunoblotting of high-mobility group protein B1,
      interleukin 6 and tumor necrosis factor-alpha proteins. Steroid treatment
      partially reversed the translations for myocarditis, CV heterogeneity, reduced
      APD at 90% recovery to baseline, increased CV (P<0.01), and reversed fibrosis
      (P<0.05). Programmed stimulation triggered sustained ventricular tachycardia in
      Myo rats (n=4/5), but not in controls (n=0/5) or Ca(2+)/calmodulin-dependent
      protein kinase II (CaMKII) inhibitor (KN93) treated Myo rats (n=0/5, P=0.01).
      CaMKII autophosphorylation at Thr287 (201%), and RyR2 phosphorylation at Ser2808
      (protein kinase A/CaMKII site, 126%) and Ser2814 (CaMKII site, 21%) were
      increased in rats with myocarditis and reversed by steroid. CONCLUSIONS: The
      myocarditis group had an increased incidence of arrhythmia caused by increased
      phosphorylation of Ca(2+)handling proteins. These changes were partially reversed
      by an antiinflammatory treatment and CaMKII inhibition.

PMID- 25056500
TI  - Association of phosphatase and tensin homolog low and phosphatidylinositol 3
      kinase catalytic subunit alpha gene mutations on outcome in human epidermal
      growth factor receptor 2-positive metastatic breast cancer patients treated with
      first-line lapatinib plus paclitaxel or paclitaxel alone.
AB  - INTRODUCTION: Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is
      PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been
      shown to enhance breast cancer cell survival and confer resistance to
      chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA
      mutations and PTEN low in patients receiving paclitaxel alone or in combination
      with lapatinib. METHODS: Immunohistochemistry and mutation analyses were used to
      evaluate PTEN and PIK3CA, respectively. Kaplan-Meier analysis with log-rank
      tests, logistic regression and Cox models were used in analyses of these
      biomarkers with efficacy endpoints. RESULTS: In the overall population, PIK3CA
      mutations were associated with poorer overall survival (OS) (hazard ratio (HR) =
      1.87; 95% confidence interval (CI): 1.22, 2.88; P = 0.001). PTEN expression was
      not associated with OS (P = 0.474). In the PIK3CA wild-type subgroup, lapatinib
      plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR =
      0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not
      significantly improved within the PIK3CA mutation subgroup (P = 0.179). In the
      PTEN low group, OS was improved with addition of lapatinib (P = 0.039). In both
      PTEN subgroups, addition of lapatinib was associated with improvements in PFS (P
      <0.050). PIK3CA and PTEN were not predictive of treatment based on interaction
      tests (P >0.05). CONCLUSIONS: PTEN was neither a significant prognostic nor
      predictive factor. PIK3CA mutations were an adverse prognostic factor for
      survival but not predictive for lapatinib benefit. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00281658 (registered 23 January 2006).

PMID- 25056501
TI  - Age and site should be considered when investigating the effect of growth factors
      on human bone-derived cells.

PMID- 25056502
TI  - Protein ingestion to stimulate myofibrillar protein synthesis requires greater
      relative protein intakes in healthy older versus younger men.
AB  - BACKGROUND: Adequate protein ingestion-mediated stimulation of myofibrillar
      protein synthesis (MPS) is required to maintain skeletal muscle mass. It is
      currently unknown what per meal protein intake is required to maximally stimulate
      the response in older men and whether it differs from that of younger men.
      METHODS: We retrospectively analyzed data from our laboratories that measured MPS
      in healthy older (~71 years) and younger (~22 years) men by primed constant
      infusion of l-ring-[(13)C6]phenylalanine after ingestion of varying amounts (0-40
      g) of high-quality dietary protein as a single bolus and normalized to body mass
      and, where available, lean body mass (LBM). RESULTS: There was no difference (p =
      .53) in basal MPS rates between older (0.027+/-0.04%/h; means +/- 95% CI) and
      young (0.028 +/- 0.03%/h) men. Biphase linear regression and breakpoint analysis
      revealed the slope of first line segment was lower (p < .05) in older men and
      that MPS reached a plateau after ingestion of 0.40 +/- 0.19 and 0.24 +/- 0.06
      g/kg body mass (p = .055) and 0.60 +/- 0.29 and 0.25 +/- 0.13 g/kg lean body mass
      (p < .01) in older and younger men, respectively. CONCLUSIONS: This is the first
      report of the relative (to body weight) protein ingested dose response of MPS in
      younger and older men. Our data suggest that healthy older men are less sensitive
      to low protein intakes and require a greater relative protein intake, in a single
      meal, than young men to maximally stimulate postprandial rates of MPS. These
      results should be considered when developing nutritional solutions to maximize
      MPS for the maintenance or enhancement of muscle mass with advancing age.

PMID- 25056503
TI  - Response to the letter "Age and site should be considered when investigating the
      effect of growth factors on human bone-derived cells".

PMID- 25056504
TI  - Comparison between the effects of intraoperative human albumin and normal saline
      on early graft function in renal transplantation.
AB  - PURPOSE: The aim of the current study was to compare the effects of
      intraoperative infusion of 20 % human albumin versus 0.9 % normal saline on early
      and late graft function in renal transplantation. METHODS: This prospective,
      randomized study was conducted on 44 patients with end-stage renal disease
      undergoing kidney transplantation. Patients were 32 males (72.7 %) and 12 females
      (27.3 %) with a mean age of 54.35 +/- 11.15 years (range 20-58 years). Patients
      with cardiac disease and liver dysfunction were excluded from the study. Twenty
      two of the 44 patients were given intraoperative intravenous infusion of 20 %
      human albumin with 0.9 % normal saline (albumin group), and the remaining 22
      patients received intraoperative intravenous infusion of 0.9 % normal saline
      alone (saline group), as part of the intraoperative fluid hydration to keep
      central venous pressure between 10 and 15 mm of Hg. RESULTS: There was no
      statistically significant difference in mean intravenous fluid volume infused
      until the end of surgery between the saline group and the albumin group (P =
      0.8326). Time of onset of diuresis and total intraoperative urine output were
      statistically insignificant between the two groups (P = 0.6255, P = 0.9231,
      respectively). Post-transplant serum creatinine on day 1, 3 and 5 between the
      albumin and saline groups were comparable (P = 0.8998, P = 0.7257, P = 0.8092,
      respectively). Post-transplant urine output on day 1, 3 and 5 between the albumin
      and saline groups were also comparable (P = 0.653, P = 0.9075, P = 0.946,
      respectively). Mean postoperative weight gain was higher in the saline group
      compared with the albumin group, but was not statistically significant (P =
      0.6348). CONCLUSIONS: This study revealed that the use of 20 % human albumin as
      an intraoperative volume expander provides no more benefit than the use of 0.9 %
      normal saline in terms of immediate graft function in living donor renal
      transplantation.

PMID- 25056505
TI  - Platelet recovery and survival measured in patients by quantitative polymerase
      chain reaction of mitochondrial DNA.
AB  - BACKGROUND: Mitochondrial (mt) DNA markers have been identified as potential
      targets for the quantification of endogenous and allogeneic platelets (PLTs) in
      the blood of individuals who received transfusions. Our goal was to develop a
      routine polymerase chain reaction (PCR) assay for ex vivo monitoring of PLT
      survival in patients after transfusion. STUDY DESIGN AND METHODS: Targets were
      selected for real-time (RT)-PCR of mt DNA based on the frequency distribution of
      nucleotide polymorphisms and assay sensitivity in vitro. The assays were then
      evaluated with ex vivo samples to measure PLT survival and recovery of
      therapeutic doses of apheresis PLTs in hematooncologic patients with
      thrombocytopenia. RESULTS: Nucleotides in two positions (73/310 hypervariable
      region [HVR] 2) and three positions (295 HVR 2, 16069/16311 HVR 1) had allele
      frequencies of approximately 0.5 and 0.85, respectively, in a population of 960
      Caucasian PLT donors. They provided targets for sensitive assays detecting at
      least 1 * 10(3) PLTs per whole blood sample with adequate reproducibility
      (interassay coefficient of variation <4.0%). Transfusions of single-donor PLT
      concentrates in patients with thrombocytopenia (n = 30) were monitored with these
      markers. The mean 24-hour corrected count increment was 8.3 and the mean
      calculated survival time was 3.3 days. Results for a second marker were available
      for 13 transfusions. The survival time values derived from both markers for the
      same transfusion were almost identical (linear regression: r(2)  = 0.957, slope =
      0.87). CONCLUSION: This RT-PCR method detects mt DNA polymorphisms in Caucasians
      for a highly sensitive and reproducible quantification of endogenous and
      allogeneic PLT numbers in blood samples from transfused patients with
      thrombocytopenia.

PMID- 25056506
TI  - Predictors for outcomes after super-selective mesenteric embolization for lower
      gastrointestinal tract bleeding.
AB  - BACKGROUND: The optimal management of bleeding from the lower gastrointestinal
      tract (LGIB) remains controversial. We aim to evaluate the efficacy of mesenteric
      embolization for LGIB and to identify predictors for re-bleeding after the
      procedure. METHODS: We conducted a retrospective review of all patients who
      underwent mesenteric embolizations for LGIB in our institution over a 6-year
      period (from August 2007 to August 2013). Technical success was defined as the
      absence of contrast extravasation on post-embolization angiogram. Clinical
      success was defined as the absence of overt LGIB (clinical bleeding with >1 g/dL
      decrease in haemoglobin) within 30 days post-embolization. RESULTS: Mesenteric
      embolization was performed in 26 patients with LGIB. Technical success rate was
      100%, with no occurrence of post-embolization ischaemia. Clinical success rate
      was 65.4%, with nine patients re-bleeding within 30 days post-embolization. Three
      underwent surgery, one underwent re-embolization and five were treated
      conservatively. Mortality rate was 19.3% (five patients), with two bleeding
      associated mortalities. Site and aetiology of LGIB, platelet count and
      coagulation status prior to embolization, number of packed red blood cells and
      fresh frozen plasma transfusion were found to be predictors of clinical failure.
      After Bonferroni's correction (P < 0.005), platelet count of <=140 * 10(9) /L
      prior to embolization was the only statistically significant factor associated
      with re-bleeding (odds ratio = 17.5, 95% confidence interval: 2.364-129.57; P =
      0.004). CONCLUSION: Mesenteric embolization was found to be safe and effective in
      treating LGIB (100% technical success, no post-embolization ischaemia), with
      65.4% of cases not requiring further intervention. Low platelet count prior to
      embolization appears to be associated with clinical failure.

PMID- 25056507
TI  - Enhancing population pharmacokinetic modeling efficiency and quality using an
      integrated workflow.
AB  - Population pharmacokinetic (popPK) analyses are at the core of Pharmacometrics
      and need to be performed regularly. Although these analyses are relatively
      standard, a large variability can be observed in both the time (efficiency) and
      the way they are performed (quality). Main reasons for this variability include
      the level of experience of a modeler, personal preferences and tools. This paper
      aims to examine how the process of popPK model building can be supported in order
      to increase its efficiency and quality. The presented approach to the conduct of
      popPK analyses is centered around three key components: (1) identification of
      most common and important popPK model features, (2) required information content
      and formatting of the data for modeling, and (3) methodology, workflow and
      workflow supporting tools. This approach has been used in several popPK modeling
      projects and a documented example is provided in the supplementary material.
      Efficiency of model building is improved by avoiding repetitive coding and other
      labor-intensive tasks and by putting the emphasis on a fit-for-purpose model.
      Quality is improved by ensuring that the workflow and tools are in alignment with
      a popPK modeling guidance which is established within an organization. The main
      conclusion of this paper is that workflow based approaches to popPK modeling are
      feasible and have significant potential to ameliorate its various aspects.
      However, the implementation of such an approach in a pharmacometric organization
      requires openness towards innovation and change-the key ingredient for evolution
      of integrative and quantitative drug development in the pharmaceutical industry. 

PMID- 25056508
TI  - Clinical features and treatment outcomes of 41 dogs with sublingual ectopic
      thyroid neoplasia.
AB  - BACKGROUND: Thyroid neoplasia is common in dogs, but there are few reports of
      dogs with ectopic, sublingual thyroid tumors. OBJECTIVES: To describe clinical
      features and outcomes of dogs with ectopic, sublingual thyroid neoplasia.
      ANIMALS: Five hundred and forty-four dogs with thyroid neoplasia. METHODS: This
      retrospective study reviewed the medical records of dogs referred for thyroid
      neoplasia between 1995 and 2013. Data extracted included signalment, extent of
      thyroid disease (eutopic or ectopic; metastasis), serum thyroxine (T4)
      concentration, treatment, and survival. RESULTS: Of 544 dogs with thyroid
      neoplasia, 41 (7.5%) dogs had ectopic sublingual thyroid tumors. The clinical
      features of these 41 dogs were similar to the cohort group of 503 dogs with
      eutopic or ectopic mediastinal thyroid tumors, but dogs with sublingual tumors
      were younger and less likely to have metastatic disease (15% versus 30%, P <
      .05). Of the 41 dogs, 28 received treatment: 21 with surgery (which included
      partial hyoidectomy in 13), 7 with radioiodine alone, and 13 with surgery
      followed by administration of radioiodine. Overall median survival was 562 days
      (range, 1-1,850 days). CONCLUSIONS AND CLINICAL IMPORTANCE: When compared with
      eutopic thyroid carcinomas, ectopic sublingual thyroid tumors generally have a
      less aggressive biologic behavior. Many dogs have prolonged survival, even
      without treatment, although death because of local tumor invasiveness or
      metastasis can develop in some dogs. Surgical thyroidectomy, including partial
      hyoidectomy, is generally effective for control of local disease. Administration
      of radioiodine, alone or in combination with surgical treatment, is recommended
      for multifocal disease or metastasis.

PMID- 25056509
TI  - The relationship between nocturnal blood pressure and hemorrhagic stroke in
      Chinese hypertensive patients.
AB  - To study the relationship between nocturnal blood pressure (BP) variation and
      spontaneous intracerebral hemorrhage (ICH) among Chinese hypertensive patients
      and its clinical significance, the authors retrospectively screened 371 patients
      with primary hypertension (189 patients with ICH, 182 patients without ICH) in
      Shanghai and analyzed their demographics, clinical information, nocturnal blood
      pressure variability and medication. Compared with the control group, the levels
      of blood glucose, triglycerides, and creatinine were significantly increased in
      the ICH group, along with a marked reduction in nocturnal BP drop (P<.05).
      Multivariate logistic regression indicated that blood glucose, creatinine, and
      nocturnal mean arterial pressure were risk factors for ICH, and the magnitude of
      nocturnal BP drop was negatively related to the risk for ICH. There was no
      significant difference in the prevalence of reverse dippers between the large
      hematoma volume group and the small hematoma volume group (chi(2) =2.529,
      P=.112), nor among the patients taking angiotensin-converting enzyme inhibitors,
      angiotensin receptor blockers, or calcium channel blockers (chi(2) =1.981,
      P=.371). Reverse dipping is associated with the risk for ICH, suggesting that
      appropriate antihypertensive drug and chronotherapy might be effective to
      normalize the rhythm of abnormal circadian variation in hypertensive patients. 

PMID- 25056510
TI  - Interest of low-dose hydrocortisone therapy during brain-dead organ donor
      resuscitation: the CORTICOME study.
AB  - INTRODUCTION: Circulatory failure during brain death organ donor resuscitation is
      a problem that compromises recovery of organs. Combined administration of
      steroid, thyroxine and vasopressin has been proposed to optimize the management
      of brain deceased donors before recovery of organs. However the single
      administration of hydrocortisone has not been rigorously evaluated in any trial.
      METHODS: In this prospective multicenter cluster study, 259 subjects were
      included. Administration of low-dose steroids composed the steroid group (n =
      102). RESULTS: Although there were more patients in the steroid group who
      received norepinephrine before brain death (80% vs. 66%: P = 0.03), mean dose of
      vasopressor administered after brain death was significantly lower than in the
      control group (1.18 +/- 0.92 mg/H vs. 1.49 +/- 1.29 mg/H: P = 0.03), duration of
      vasopressor support use was shorter (874 min vs. 1160 min: P < 0.0001) and
      norepinephrine weaning before aortic clamping was more frequent (33.8% vs. 9.5%:
      P < 0.0001). Using a survival approach, probability of norepinephrine weaning was
      significantly different between the two groups (P < 0.0001) with a probability of
      weaning 4.67 times higher in the steroid group than in the control group (95% CI:
      2.30 - 9.49). CONCLUSIONS: Despite no observed benefits of the steroid
      administration on primary function recovery of transplanted grafts,
      administration of glucocorticoids should be a part of the resuscitation
      management of deceased donors with hemodynamic instability.

PMID- 25056512
TI  - The effect of HIV infection on the incidence and severity of circular external
      fixator pin track sepsis: a retrospective comparative study of 229 patients.
AB  - Pin track sepsis is a common complication of circular external fixation. HIV
      status has been implicated as an independent risk factor for the development of
      pin track infection and has been cited as a reason not to attempt complex limb
      reconstruction in HIV-positive patients. This retrospective review of patients
      treated with circular external fixators looked at the incidence of pin track
      sepsis in HIV-positive, HIV-negative and patients whose HIV status was unknown.
      The records of 229 patients, 40 of whom were HIV-positive, were reviewed. The
      overall incidence of pin track sepsis was 22.7 %. HIV infection did not affect
      the incidence of pin track sepsis (p = 0.9). The severity of pin track sepsis was
      not influenced by HIV status (p = 0.9) or CD4 count (p = 0.2). With the
      employment of meticulous pin insertion techniques and an effective postoperative
      pin track care protocol, circular external fixation can be used safely in HIV
      positive individuals. 

PMID- 25056513
TI  - Nailing treatment in bone transport complications.
AB  - A series of cases of reamed intramedullary nailings carried out after
      complications in regenerated bone and docking site had occurred in bone transport
      is presented here. Nine patients (femur = 5; tibia = 4) had treatment with
      resection after open fractures or infection and underwent bone transport. The
      mean length of regenerated bone was 9.5 cm (range 6-18 cm). After bone transport,
      the fixator remained in place for a mean period of 12.8 months (range 8-24
      months). In six cases (femur 4; tibia 2), the thickness of the cortical wall of
      the regenerate column was insufficient, and in two of these, there was, in
      addition, nonunion of the docking site. In the two tibial cases, nailing was
      carried out shortly after the fixator had been removed and after refracture of
      the regenerated bone had occurred due to insufficient cortical thickness. In one
      femur, nailing was carried out for nonunion of the docking site. Follow-up
      involved clinical and X-ray checks. The mean follow-up was 3.9 years (range 2-6
      years). In all cases, union and with complete corticalization of the regenerate
      column was observed at an average 6 months after nailing (range 4-11 months).
      Infection occurred in one tibia 4 months after nailing. The infection was treated
      with antibiotics, and the nail was subsequently removed. We conclude that nailing
      is a potential solution for regenerated bone and docking site problems but, if
      used after prolonged periods of external fixation, may necessitate antibiotic
      therapy for at least 10 days after the fixator has been removed. 

PMID- 25056515
TI  - The effect of cypermethrin, chlorpyrifos, and glyphosate active ingredients and
      formulations on Daphnia magna (Straus).
AB  - Acute effects of active ingredients (a.i.) and formulations (F) of widely used
      pesticides were assessed by means of the Daphnia magna toxicity test. Studied
      pesticides were the insecticides, cypermethrin and chlorpyrifos, and the
      herbicide, glyphosate. Results were analyzed and compared according to
      statistical endpoints (LCx) and log-probit regressions of toxicity data. The
      potency of acute toxicity followed the order: chlorpyrifos F > chlorpyrifos a.i.
      > cypermethrin F > cypermethrin a.i. ? glyphosate F > glyphosate a.i. Three to
      five orders of magnitude differences between the toxicity (ug/L to mg/L) of
      insecticides and the herbicide were observed. A pairwise comparison between a.i.
      and F indicated that all formulations were more potent. Additionally, for the
      case of glyphosate, evidence suggests that the adjuvant contributes to
      formulation toxicity rather than to the enhancement of a.i. potency.

PMID- 25056511
TI  - Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE
      Studies (SOCRATES).
AB  - AIMS: The clinical outcomes for patients with worsening chronic heart failure
      (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and
      effective therapies are urgently needed. Accumulating evidence supports
      augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential
      therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF
      and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators
      target reduced cGMP generation due to insufficient sGC stimulation and represent
      a promising method for cGMP enhancement. METHODS: The phase II SOluble guanylate
      Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two
      randomized, parallel-group, placebo-controlled, double-blind, multicentre
      studies, SOCRATES-REDUCED (in patients with LVEF <45%) and SOCRATES-PRESERVED (in
      those with LVEF >= 45%), that will explore the pharmacodynamic effects, safety
      and tolerability, and pharmacokinetics of four dose regimens of the once-daily
      oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo.
      These studies will enrol patients stabilized during hospitalization for HF at the
      time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES
      REDUCED is change in NT-proBNP at 12 weeks. The primary endpoints in SOCRATES
      PRESERVED are change in NT-proBNP and left atrial volume at 12 weeks.
      PERSPECTIVES: SOCRATES will be the first programme to enrol specifically both
      inpatients and outpatients with WCHF and patients with reduced or preserved
      ejection fraction. Results will inform the benefits of pursuing subsequent event
      driven clinical outcome trials with sGC stimulators in this patient population.

PMID- 25056516
TI  - The challenge of objective confirmation of asthma diagnosis in primary care.
AB  - Asthma represents one of the most common chronic conditions encountered in
      primary care and diagnosis should be confirmed objectively with the demonstration
      of variable airflow obstruction. As many asthmatics have normal lung function at
      the time of clinical presentation, objective confirmation of airflow limitation
      may be challenging. Fluctuations in airflow obstruction can be documented with
      simple office spirometry after bronchodilator challenge, home monitoring of peak
      expiratory flow and bronchoconstriction induced by spasmogens such as
      methacholine. We present a case highlighting the challenge of objective
      confirmation of asthma diagnosis in primary care and provide a critical review of
      the diagnostic approaches highlighted above. Our aim is to provide a pragmatic
      interpretation of the available literature with a view to assisting clinicians in
      selecting the diagnostic test best suited for individualised patient encounters. 

PMID- 25056514
TI  - Targeting mitochondrially mediated plasticity to develop improved therapeutics
      for bipolar disorder.
AB  - INTRODUCTION: Bipolar disorder (BPD) is a severe illness with few treatments
      available. Understanding BPD pathophysiology and identifying potential relevant
      targets could prove useful for developing new treatments. Remarkably, subtle
      impairments of mitochondrial function may play an important role in BPD
      pathophysiology. AREAS COVERED: This article focuses on human studies and reviews
      evidence of mitochondrial dysfunction in BPD as a promising target for the
      development of new, improved treatments. Mitochondria are crucial for energy
      production, generated mainly through the electron transport chain (ETC) and play
      an important role in regulating apoptosis and calcium (Ca2+) signaling as well as
      synaptic plasticity. Mitochondria move throughout the neurons to provide energy
      for intracellular signaling. Studies showed polymorphisms of mitochondria-related
      genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC
      activity/expression and increased nitrosative and oxidative stress (OxS) in
      patient brains. BPD has been also associated with increased OxS, Ca2+
      dysregulation and increased proapoptotic signaling in peripheral blood.
      Neuroimaging studies consistently show decreased energy levels and pH in brains
      of BPD patients. EXPERT OPINION: Targeting mitochondrial function, and their role
      in energy metabolism, synaptic plasticity and cell survival, may be an important
      avenue for development of new mood-stabilizing agents.

PMID- 25056518
TI  - Organic superhalogens.
AB  - Using first-principles calculations with predictive capability we show that
      organic molecules having negative electron affinity can be transformed to
      superhalogens with electron affinities far exceeding that of chlorine, once its
      core and ligand atoms are suitably replaced. The discovery of organic
      superhalogens could have significant impact in chemistry, allowing the synthesis
      of new materials and compounds. 

PMID- 25056517
TI  - Maternal near-miss and death and their association with caesarean section
      complications: a cross-sectional study at a university hospital and a regional
      hospital in Tanzania.
AB  - BACKGROUND: The maternal near-miss (MNM) concept has been developed to assess
      life-threatening conditions during pregnancy, childhood, and puerperium. In
      recent years, caesarean section (CS) rates have increased rapidly in many low-
      and middle-income countries, a trend which might have serious effects on maternal
      health. Our aim was to describe the occurrence and panorama of maternal near-miss
      and death in two low-resource settings, and explore their association with CS
      complications. METHODS: We performed a cross-sectional study, including all women
      who fulfilled the WHO criteria for MNM or death between February and June 2012 at
      a university hospital and a regional hospital in Dar es Salaam, Tanzania. Cases
      were assessed individually to determine their association with CS. Main outcome
      measures included MNM ratio; maternal mortality ratio; proportion of MNM and
      death associated with CS complications; and the risk for such outcomes per 1,000
      operations. The risk ratio of life-threatening CS complications at the university
      hospital compared to the regional hospital was calculated. RESULTS: We identified
      467 MNM events and 77 maternal deaths. The MNM ratio was 36 per 1,000 live births
      (95% CI 33-39) and the maternal mortality ratio was 587 per 100,000 live births
      (95% CI 460-730). Major causes were eclampsia and postpartum haemorrhage, but we
      also detected nine MNM events and five deaths from iatrogenic complications. CS
      complications accounted for 7.9% (95% CI 5.6-11) of the MNM events and 13% (95%
      CI 6.4-23) of the maternal deaths. The risk of experiencing a life-threatening CS
      complication was three times higher at the regional hospital (22/1,000
      operations, 95% CI 12-37) compared to the university hospital (7.0/1,000
      operations, 95% CI 3.8-12) (risk ratio 3.2, 95% CI 1.5-6.6). CONCLUSIONS: The
      occurrence of MNM and death at the two hospitals was high, and many cases were
      associated with CS complications. The maternal risks of CS in low-resource
      settings must not be overlooked, and measures should be taken to avoid
      unnecessary CSs. More comprehensive training of staff, improved postoperative
      surveillance, and a more even distribution of resources within the health care
      system might reduce the risks of CS.

PMID- 25056519
TI  - Sorption-determined deposition of platinum on well-defined platelike WO3.
AB  - The photodeposition of Pt nanoparticles from [PtCl6 ](2-) on platelike WO3
      crystals occurs preferentially on the small, subordinate facets. Rather than the
      often-used explanation of preferred light-induced charge migration, we propose
      that this phenomenon is due to differences in the intrinsic surface charges of
      WO3 facets exposed to water; thus, the dark sorption of [PtCl6 ](2-) on
      positively charged facets/edges is preferred. This conclusion is based on 1)
      (dark) impregnation studies, which showed Pt deposition to also be facet
      specific, and 2) aqueous-phase AFM studies, which suggest intrinsic surface
      charges to be in agreement with sorption-based Pt distributions. 

PMID- 25056520
TI  - Spatial-temporal variation of marginal land suitable for energy plants from 1990
      to 2010 in China.
AB  - Energy plants are the main source of bioenergy which will play an increasingly
      important role in future energy supplies. With limited cultivated land resources
      in China, the development of energy plants may primarily rely on the marginal
      land. In this study, based on the land use data from 1990 to 2010(every 5 years
      is a period) and other auxiliary data, the distribution of marginal land suitable
      for energy plants was determined using multi-factors integrated assessment
      method. The variation of land use type and spatial distribution of marginal land
      suitable for energy plants of different decades were analyzed. The results
      indicate that the total amount of marginal land suitable for energy plants
      decreased from 136.501 million ha to 114.225 million ha from 1990 to 2010. The
      reduced land use types are primarily shrub land, sparse forest land, moderate
      dense grassland and sparse grassland, and large variation areas are located in
      Guangxi, Tibet, Heilongjiang, Xinjiang and Inner Mongolia. The results of this
      study will provide more effective data reference and decision making support for
      the long-term planning of bioenergy resources. 

PMID- 25056521
TI  - An easy one-pot synthesis of diverse 2,5-di(2-pyridyl)pyrroles: a versatile entry
      point to metal complexes of functionalised, meridial and tridentate 2,5-di(2
      pyridyl)pyrrolato ligands.
AB  - A wide variety of 2,5-di(2-pyridyl)pyrroles (dppHs) substituted at the C3 and C4
      positions of the pyrrole core were obtained by direct condensation of a 2
      pyridylcarboxaldehyde (2 equiv), an alpha-methylene ketone with at least one
      electron-withdrawing substituent and ammonium acetate. A novel 2,5-di(1,10
      phenanthrolin-2-yl)pyrrole was also characterised. The dppHs provide a direct,
      quick entry to dipyridylpyrrolato (dpp(-) )-metal complexes. The meridial
      tridentate dpp(-) ligand is a useful anionic analogue of the terpyridyl ligand.
      The first (dpp)Ru complexes are described; the 3,4-substitution of the central
      pyrrole significantly perturbs the potentials of the redox processes of these
      complexes. A [(dpp)Ru(bpy)(MeCN)](+) (bpy=2,2'-bipyridine) complex is an
      electrocatalyst for the reductive disproportionation of carbon dioxide to carbon
      monoxide and the carbonate ion. 

PMID- 25056522
TI  - Complications of pelvic radiation in patients treated for gynecologic
      malignancies.
AB  - Radiation therapy is a critical treatment modality in the management of patients
      with gynecologic tumors. New highly conformal external-beam and brachytherapy
      techniques have led to important reductions in recurrence and patient morbidity
      and mortality. However, patients who receive pelvic radiation for gynecologic
      malignancies may experience a unique constellation of toxicity because of the
      anatomic locations, combination with concurrent chemotherapy and/or surgery, as
      well as potential surgical interventions. Although side effects are often
      categorized into acute versus late toxicities, several late toxicities represent
      continuation and evolution of the same pathologic process. Comorbidities and
      radiation dose can significantly increase the risk of morbidity. Current
      understanding of the incidence of various morbidities in patients treated with
      current radiation techniques for gynecologic malignancies, the impact of
      chemotherapy and surgery, treatment options for those effects, and future areas
      of research are highlighted.

PMID- 25056523
TI  - Sex determination in Madagascar geckos of the genus Paroedura (Squamata:
      Gekkonidae): are differentiated sex chromosomes indeed so evolutionary stable?
AB  - Among amniote vertebrates, geckos represent a clade with exceptional variability
      in sex determination; however, only a minority of species of this highly diverse
      group has been studied in this respect. Here, we describe for the first time a
      female heterogamety in the genus Paroedura, the group radiated in Madagascar and
      adjacent islands. We identified homomorphic ZZ/ZW sex chromosomes with a highly
      heterochromatic W chromosome in Paroedura masobe, Paroedura oviceps, Paroedura
      karstophila, Paroedura stumpffi, and Paroedura lohatsara. Comparative genomic
      hybridization (CGH) revealed that female-specific sequences are greatly amplified
      in the W chromosome of P. lohatsara and that P. gracilis seems to possess a
      derived system of multiple sex chromosomes. Contrastingly, neither CGH nor
      heterochromatin visualization revealed differentiated sex chromosomes in the
      members of the Paroedura picta-Paroedura bastardi-Paroedura ibityensis clade,
      which is phylogenetically nested within lineages with a heterochromatic W
      chromosome. As a sex ratio consistent with genotypic sex determination has been
      reported in P. picta, it appears that the members of the P. picta-P. bastardi-P.
      ibityensis clade possess homomorphic, poorly differentiated sex chromosomes and
      may represent a rare example of evolutionary loss of highly differentiated sex
      chromosomes. Fluorescent in situ hybridization (FISH) with a telomeric probe
      revealed a telomere-typical pattern in all species and an accumulation of
      telomeric sequences in the centromeric region of autosomes in P. stumpffi and P.
      bastardi. Our study adds important information for the greater understanding of
      the variability and evolution of sex determination in geckos and demonstrates how
      the geckos of the genus Paroedura provide an interesting model for studying the
      evolution of the sex chromosomes. 

PMID- 25056524
TI  - CAST: a new program package for the accurate characterization of large and
      flexible molecular systems.
AB  - The presented program package, Conformational Analysis and Search Tool (CAST)
      allows the accurate treatment of large and flexible (macro) molecular systems.
      For the determination of thermally accessible minima CAST offers the newly
      developed TabuSearch algorithm, but algorithms such as Monte Carlo (MC), MC with
      minimization, and molecular dynamics are implemented as well. For the
      determination of reaction paths, CAST provides the PathOpt, the Nudge Elastic
      band, and the umbrella sampling approach. Access to free energies is possible
      through the free energy perturbation approach. Along with a number of standard
      force fields, a newly developed symmetry-adapted perturbation theory-based force
      field is included. Semiempirical computations are possible through DFTB+ and
      MOPAC interfaces. For calculations based on density functional theory, a Message
      Passing Interface (MPI) interface to the Graphics Processing Unit (GPU)
      accelerated TeraChem program is available. The program is available on request.

PMID- 25056525
TI  - Contrast sensitivity measured by two different test methods in healthy, young
      adults with normal visual acuity.
AB  - PURPOSE: This study reports contrast sensitivity (CS) reference values obtained
      by two different test methods in a strictly selected population of healthy, young
      adults with normal uncorrected visual acuity. Based on these results, the index
      of contrast sensitivity (ICS) is calculated, aiming to establish ICS reference
      values for this population and to evaluate the possible usefulness of ICS as a
      tool to compare the degree of agreement between different CS test methods.
      METHODS: Military recruits with best eye uncorrected visual acuity 0.00 LogMAR or
      better, normal colour vision and age 18-25 years were included in a study to
      record contrast sensitivity using Optec 6500 (FACT) at spatial frequencies of
      1.5, 3, 6, 12 and 18 cpd in photopic and mesopic light and CSV-1000E at spatial
      frequencies of 3, 6, 12 and 18 cpd in photopic light. Index of contrast
      sensitivity was calculated based on data from the three tests, and the Bland
      Altman technique was used to analyse the agreement between ICS obtained by the
      different test methods. RESULTS: A total of 180 recruits were included. Contrast
      sensitivity frequency data for all tests were highly skewed with a marked ceiling
      effect for the photopic tests. The median ICS for Optec 6500 at 85 cd/m2 was 
      0.15 (95% percentile 0.45), compared with -0.00 (95% percentile 1.62) for Optec
      at 3 cd/m2 and 0.30 (95% percentile 1.20) FOR CSV-1000E. The mean difference
      between ICSFACT 85 and ICSCSV was -0.43 (95% CI -0.56 to -0.30, p<0.00) with
      limits of agreement (LoA) within -2.10 and 1.22. The regression line on the
      difference of average was near to zero (R2=0.03). CONCLUSION: The results provide
      reference CS and ICS values in a young, adult population with normal visual
      acuity. The agreement between the photopic tests indicated that they may be used
      interchangeably. There was little agreement between the mesopic and photopic
      tests. The mesopic test seemed best suited to differentiate between candidates
      and may therefore possibly be useful for medical selection purposes.

PMID- 25056526
TI  - Serum cytokines as biomarkers for age-related macular degeneration.
AB  - PURPOSE: This study evaluates the potential of serum pro-inflammatory cytokines
      as AMD biomarkers. METHODS: Serum samples from 30 age-related macular
      degeneration (AMD) patients and 15 age-matched controls were examined for 16
      inflammatory cytokines using multiplex ELISA. Patients were divided into three
      subgroups (improvement/no change/deterioration during anti-VEGF treatment) by OCT
      and funduscopy, and correlated to the cytokine levels. RESULTS: Serum
      concentrations of IL-1alpha, IL-1beta, IL-4, IL-5, IL-10, IL-13, and IL-17 were
      significantly higher in AMD patients than in controls. None of the co-variables
      expressed a significant effect on the tested cytokines. Only IL-1a and IL-17
      showed a statistically significant difference between groups (improved,
      unchanged, deteriorated) as determined by one-way ANOVA. Patients with increased
      macular thickness during treatment showed significantly lower levels of IL-17
      compared to improved cases and to unchanged cases (p = 0.004, 0.03 respectively,
      Dunnett's T3 post hoc multiple test). TNF-alpha was significantly higher in
      improved cases compared to deteriorated cases (p =0.03, Dunnett's T3 post hoc
      multiple test). IL-17 was a significant predictor for macular oedema using linear
      regression (beta = -0.888, p <0.05). CONCLUSION: Elevation of IL-1alpha, IL
      1beta, IL-4, IL-5, IL-10, IL-13, and IL-17 in the serum of AMD patients supports
      the hypothesis of AMD as an inflammatory disease. Patients with high IL-17 and
      TNF-alpha serum levels were more likely to have a favourable course under VEGF
      therapy. These cytokines may be used as easy-to-obtain biomarkers.

PMID- 25056527
TI  - Posterior segment findings of ocular cytomegalovirus infection in immunocompetent
      patients.
AB  - PURPOSE: We sought to investigate and describe the clinical spectrum of posterior
      segment abnormalities in immunocompetent patients presenting with CMV-associated
      anterior uveitis. METHODS: This was a prospective study conducted at the
      Singapore National Eye Centre, a tertiary referral centre, from August 2010 to
      June 2011. Eleven eyes of eleven patients with CMV anterior uveitis confirmed by
      polymerase chain reaction on aqueous humor sampling were recruited based on the
      study criteria. Patients were recruited from a single uveitis specialist clinic
      and underwent aqueous humor sampling and fluorescein and indocyanine green
      angiography as well as optical coherence tomography. They were further evaluated
      by the Infectious Disease physician for immunocompetence. RESULTS: Mean
      presenting visual acuity was logMAR 0.35 +/- 0.29. The main presenting complaints
      were blurring of vision, eye redness, and pain. Anterior chamber cellular
      activity was present in all cases. Fine diffuse keratic precipitates (KPs) were
      present in 10 eyes, and the remaining one eye had mutton fat KPs. Iris changes
      were present in three eyes. Intraocular pressure (IOP) was elevated in nine eyes
      (mean presenting IOP was 40.2 +/- 16.8 mmHg). In the posterior segment, none of
      the eyes had evidence of retinitis or hemorrhage. Posterior segment abnormalities
      were present in six eyes (macular edema, disc leakage, epiretinal membrane,
      phlebitis). Eight eyes also had prolonged arm to retina time (mean 24.8 +/- 10.6
      s) on fluorescein angiography. Indocyanine green angiography was unremarkable.
      CONCLUSION: Posterior segment manifestations can be seen in a proportion of
      immunocompetent patients with CMV anterior uveitis. The underlying mechanism
      remains to be determined.

PMID- 25056528
TI  - Long-term effectiveness of vitrectomy in diabetic cystoid macular edema.
AB  - BACKGROUND: The aim of this study is to assess whether the outcome of pars plana
      vitrectomy for the treatment of cystoid non-tractional diabetic macular edema is
      stable and durable. METHODS: A prospective longitudinal analysis of central
      macular thickness and visual acuity was performed, using repeated-measures ANOVA,
      in 22 subjects with cystoid diabetic macular edema. RESULTS: Of the patients,
      45.5 % met the criteria for surgical success at 6 months (achieving a reduction
      of central macular thickness of over 20 %, without associated loss of vision and
      central macular thickness less than 300 MUm), of which 70 % remained stable at 1
      year. A significant outcome of the intervention was found on central macular
      thickness (p < 0.01), but not on visual acuity (p = 0.159). This change occurred
      in the immediate postoperative period to remain stable thereafter. CONCLUSIONS:
      Vitreoretinal surgery can be an alternative treatment option in cases that do not
      respond to other types of treatment provided. Its expected benefit is observed in
      most cases in the immediate postoperative period, and is usually stable and
      sustained over 1-year follow-up.

PMID- 25056529
TI  - Regionally dependent neuromuscular functions of motilin and 5-HT4 receptors in
      human isolated esophageal body and gastric fundus.
AB  - BACKGROUND: Motilin agonists promote human gastric motility and cholinergic
      activity, but excitatory and inhibitory actions are reported in the esophagus.
      The effect of 5-HT4 agonists in esophagus is also unclear. Perhaps the use of
      drugs with additional actions explains the variation. The aim, therefore, was to
      examine how motilin and prucalopride, selective motilin and 5-HT4 receptor
      agonists, modulate neuromuscular functions in human esophagus and gastric fundus.
      METHODS: Electrical field stimulation (EFS) evoked nerve-mediated contractions of
      circular and longitudinal muscle from human esophageal body and circular muscle
      from gastric fundus. KEY RESULTS: In esophageal circular muscle EFS evoked brief
      contraction, followed by another contraction on termination of EFS, each
      prevented by atropine. Nitric oxide synthase inhibition facilitated contraction
      during EFS and the overall contraction became monophasic. In esophagus
      longitudinal muscle and gastric fundus, EFS evoked cholinergically mediated,
      monophasic contractions, attenuated by simultaneous nitrergic activation. Motilin
      (100-300 nM) reduced esophagus circular muscle contractions during EFS,
      unaffected by L-NAME or apamin. Motilin 300 nM also reduced EFS-evoked
      contractions of longitudinal muscle. Similar concentrations of motilin
      facilitated cholinergic activity in the fundus and increased baseline muscle
      tension. Prucalopride facilitated EFS-evoked contractions in esophagus (tested at
      30 MUM) and fundus (0.1-30 MUM). CONCLUSIONS & INFERENCES: Selective motilin and
      5-HT4 agonists have different, region-dependent abilities to modulate human
      esophageal and stomach neuromuscular activity, exemplified by weak inhibition
      (motilin) or excitation (5-HT4) in esophageal body and excitation for both in
      stomach. In different patients with motility dysfunctions, motilin and 5-HT4
      agonists may reduce gastro-esophageal reflux in different ways.

PMID- 25056532
TI  - Vitamin E and essential polyunsaturated fatty acids supplementation in
      schizophrenia patients treated with haloperidol.
AB  - OBJECTIVES: Previously, oxidative damage has been associated with severity of
      clinical symptoms and supplementation with antioxidants and essential
      polyunsaturated fatty acids (EPUFAs) was proposed to have beneficial effects in
      schizophrenia. We evaluated the effects of supplementation with EPUFAs and
      vitamin E in patients treated with haloperidol depot injection. DESIGN: This was
      a double-blind randomized placebo-controlled study with four arms (Placebo,
      vitamin E, EPUFAs, and vitamin E + EPUFAs). Biomarkers of oxidative stress,
      neurochemistry, psychopathology, and extrapyramidal symptoms were assessed at
      baseline and after 4 months. RESULTS: In EPUFAs group of patients, reduced
      glutathione concentration was increased compared to placebo. Concentration of
      oxidized glutathione was decreased in patients receiving vitamin E. In addition,
      compared to placebo a non-significant trend of increased activity of catalase and
      superoxide dismutase was observed in all three treatment groups. Patients
      receiving vitamin E experienced less motor retardation. No difference in
      extrapyramidal symptoms was found. DISCUSSION: Our study indicates that
      supplementation with vitamin E and EPUFAs may improve the antioxidative defense,
      especially glutathione system, while there is no major effect on symptoms
      severity. Supplemental treatment with EPUFAs and vitamin E in schizophrenia
      patients treated with haloperidol is potentially beneficial and a larger
      independent study appears warranted.

PMID- 25056533
TI  - Endothelial cell-specific molecule-1: a potential serum marker for gastric
      cancer.
AB  - No ideal serum markers for gastric cancer (GC) screening have been identified.
      The aim of this study was to determine the usefulness of endothelial cell
      specific molecule-1 (ESM-1) as a serum marker for GC. The ESM-1 levels in serum
      specimens from 114 patients with GC and 55 health subjects were measured using a
      sandwich ELISA kit. Receiver operating characteristic (ROC) curve was calculated
      to assess the diagnostic value of ESM-1. Survival curves by the Kaplan-Meier
      method were plotted to display overall survival distributions. Univariable and
      multivariable Cox regression analyses were performed to assess independent
      prognostic factors for overall survival in GC. We showed that the ESM-1 levels in
      the serum of patients with GC (83.7 +/- 16.2 pg/mL) were significantly elevated
      compared to health subjects (44.7 +/- 16.4 pg/mL). The accuracy, sensitivity, and
      specificity of ESM-1 for GC were 0.946, 98, and 80 %, respectively, by ROC curve
      analysis. The positive and negative predictive values were 91 and 93.6 %,
      respectively. The likelihood ratios of a positive or negative test result were
      20.9 and 0.14, respectively. When analyzed with a Cox regression model, a higher
      serum ESM-1 level (>=84.2 pg/mL) was correlated with poor prognosis. This study
      suggests that serum ESM-1 level is increased in patients with GC and that ESM-1
      can be used as a potential serum marker for early detection and prognosis
      evaluation of GC.

PMID- 25056534
TI  - Phosphorylated p38, a negative prognostic biomarker, complements TNM staging
      prognostication in colorectal cancer.
AB  - Phosphorylated p38 (p-p38) played a pivotal role in the regulation of disease
      progression and correlated with tumor prognosis. Here, we characterized the
      prognostic effect of p-p38 in colorectal cancer (CRC). Three hundred and sixteen
      CRC patients in stages I-III were recruited in this study. P-p38 expression was
      semi-quantitatively evaluated using tissue microarrays and immunohistochemistry
      staining. Overall survival (OS), disease-free survival (DFS), local failure-free
      survival (LFFS), and distant metastasis-free survival (DMFS) of patient
      subgroups, segregated by p-p38 expression level and clinical stage, were compared
      using Kaplan-Meier analysis. We found that p-p38 was overexpressed in 48.1 %
      (152/316) CRC tissues, whereas low or deficiently expressed in normal adjacent
      epithelia. Overexpression of p-p38 predicted poor OS (P < 0.001), DFS (P =
      0.002), LFFS (P = 0.016), and DMFS (P = 0.025) in CRC. Importantly, patient
      subgroups in the early stage (stages I + II) and with low p-p38 had similar OS,
      PFS, LFFS, and DMFS probabilities to that of stage I, whereas those with high p
      p38 were similar to stage III disease. In addition, for stage III disease, the
      subgroup with low p-p38 had a similar survival probability to that of stage I,
      whereas the subgroup with high p-p38 had the worst survival. Multivariate Cox
      analysis confirmed that p-p38 was indeed a significantly independent factor for
      death, recurrence, and distant metastases in CRC. Our results demonstrated that p
      p38 was a negative independent prognostic factor for CRC. Complementing TNM
      staging with p-p38 might refine the risk definition more accurately for a subset
      of patients.

PMID- 25056535
TI  - Promoter methylation and polymorphism of E-cadherin gene may confer a risk to
      prostate cancer: a meta-analysis based on 22 studies.
AB  - Emerging evidence has suggested that -160C/A polymorphism and promoter
      methylation of E-cadherin gene may contribute to the risk of prostate cancer.
      However, the results are still conflicting. We aim to systematically evaluate the
      potential of promoter methylation and polymorphism in E-cadherin gene to confer a
      risk to prostate cancer through meta-analysis. PubMed, Embase, Web of Science,
      Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) databases
      were searched to identify eligible studies published before April 1, 2014. Pooled
      odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were calculated
      by using the random-effect model or the fixed-effect model, according to
      heterogeneity test. Subgroup analyses were also performed to explore the
      potential sources of heterogeneity. Sensitivity and publication bias analyses
      were used to test the robustness of our results. We performed a meta-analysis of
      22 included studies, with 11 on -160C/A polymorphism and another 11 on promoter
      methylation of E-cadherin gene. Our meta-analysis results suggested that E
      cadherin -160C/A polymorphism may be a potential risk factor for prostate cancer.
      Furthermore, we observed that the frequencies of promoter methylation of E
      cadherin gene in the prostate cancer tissues were significantly higher than those
      of normal tissues, indicating that promoter methylation of E-cadherin gene may
      play an important role in prostate carcinogenesis. In conclusion, the present
      meta-analysis provides further evidence that promoter methylation and -160C/A
      polymorphism of E-cadherin gene may confer a risk to prostate cancer. Identifying
      these risk factors for prostate cancer will improve early detection, allow for
      selective chemoprevention, and provide further insights into its disease
      mechanisms.

PMID- 25056536
TI  - Targeting SMAD3 for inhibiting prostate cancer metastasis.
AB  - Although SMAD3 signaling has been suggested to play a role in the metastasis of
      various cancers, its possible involvement as well as the underlying mechanism in
      the pathogenesis in prostate cancer remains unclear. Here, we found that the MMP9
      level, an indicator of the invasiveness of cancer cells, negatively correlates
      with the activity of phosphorylated SMAD3 levels in the prostate cancer patients.
      Moreover, the phosphorylated SMAD3 also appeared to regulate the MMP9 level in a
      prostate cancer cell line, PC3. Augmented phosphorylated SMAD3 inhibited MMP9 and
      invasiveness of PC3 cells, while inhibition of phosphorylated SMAD3 activated
      MMP9 and promoted PC3 cell invasiveness. Furthermore, forced MMP9 inhibition
      abolished the effect of phosphorylated SMAD3 on the invasiveness of PC3 cells,
      while forced MMP9 activation abolished the effect of phosphorylated SMAD3 on the
      invasiveness of PC3 cells. Taken together, our data suggest the possibility of
      the existence of a unique signaling cascade in which SMAD3 signaling regulates
      MMP9 during cancer metastasis.

PMID- 25056537
TI  - A mixed anti-inflammatory and pro-inflammatory response associated with a high
      dose of corticosteroids.
AB  - OBJECTIVE: Hydrocortisone, at a low dose (100 mg), induces an anti-inflammatory
      response including inducing IkBalpha and suppressing intranuclear NFkappaB and AP
      1 binding and the expression of pro-inflammatory mediators like MMPs. We have now
      investigated the effect of a high dose of hydrocortisone (300mg=60 mg
      prednisolone) on NFkappaB binding and the expression of TLRs, the mediators of
      TLR signal transduction, MyD88 and TRIF and HMG-B1. DESIGN AND SUBJECTS: A 300mg
      of hydrocortisone or saline was injected intravenously in ten normal subjects
      during 2 separate visits, in a randomized crossover study. Blood samples were
      obtained at 0, 1, 4, 6 and 24h after the injection and mononuclear cells (MNC)
      were prepared. RESULTS: There was a significant increase in glucose (from 92+/-4
      to 116+/-6 mg/dl), insulin (from 4.5+/-0.7 to 5.3+/-0.8 mU/ml) and FFA
      concentrations (from 0.38+/-0.1 to 0.80+/-0.15mM) following the administration of
      hydrocortisone compared to placebo treatment. While NFkappaB binding and the mRNA
      expression of MyD88, TRIF, chemokines and chemokine receptors were suppressed
      significantly in MNC, there was a paradoxical increase in the mRNA expression of
      TLR 2, 5 and 9 and HMG-B1 was increased by 103+/-24%, 107+/-19%, 56+/-13% and
      58+/-12% above the baseline, respectively in the MNC. Plasma concentrations of
      HMG-B1 and MMP-9 increased by 37+/-12% and 125+/-22%, respectively, while TNF
      alpha concentrations fell by 27+/-9%. CONCLUSION: While this high dose of
      hydrocortisone exerts a powerful anti-inflammatory effect, it also exerts certain
      proinflammatory effects mainly on TLRs expression. The known pro-inflammatory
      effects of glucose and FFAs may have contributed to these effects. These
      paradoxical pro-inflammatory effects may account for the inability of these drugs
      to show benefit in clinical trials of septicemia and other severe pro
      inflammatory states and might contribute to some of the side effects of
      corticosteroids use.

PMID- 25056538
TI  - Upregulation of cytoskeleton protein and extracellular matrix protein induced by
      stromal-derived nitric oxide promotes lung cancer invasion and metastasis.
AB  - Lung cancer commonly metastasizes to lymph nodes, brain and bones, which is the
      main cause of death. It is still a challenge to detect molecular biomarkers for
      early diagnosis and therapeutics of lung cancer. Our previous study found that
      bone marrow-derived stroma cells (BMSCs) under tumor microenvironment produced
      nitric oxide (NO), which was induced by inducible nitric oxide synthase (iNOS),
      and promoted invasion and metastasis of cancer cells by remodeling cytoskeleton.
      The aim of this study is to elucidate the relationship between the expressions of
      iNOS, cytoskeleton protein caldesmon, OPN, and clinical parameters especially the
      metastasis of lung cancer. We found that nitric oxide can remodel cytoskeleton
      and promoted the mobility of lung cancer cells. The expressions of iNOS,
      caldesmon, and OPN are closely correlated to metastasis of lung cancer. The
      intracranial metastatic tissue samples of lung cancer showed significantly higher
      expression of iNOS, caldesmon and OPN. A flow-cytometry analysis for peripheral
      blood of lung cancer patients showed increased EPCAM+/OPN+ cells in circulation
      of patients with bone metastasis compared to that of patients without metastasis,
      which is indicative of cancer circulating cells. The concentration of serum OPN
      was also positively related to the bone metastasis of lung cancer. Taken
      together, these results suggested that iNOS, caldesmon and OPN may work as
      biomarkers for metastasis of lung cancer. 

PMID- 25056539
TI  - Hepatocyte FRS2alpha is essential for the endocrine fibroblast growth factor to
      limit the amplitude of bile acid production induced by prandial activity.
AB  - In addition to being positively regulated by prandial activity, bile acid
      production is also negatively controlled by the endocrine fibroblast growth
      factor 19 (FGF19) or the mouse ortholog FGF15 from the ileum that represses
      hepatic cholesterol 7 alpha-hydroxylase (Cyp7a1) expression through activating
      FGF receptor four (FGFR4). However, how these two regulatory mechanisms interplay
      to control bile acid homeostasis in the body and the downstream pathways by which
      FGFR4 regulates Cyp7a1 expression are not fully understood. Here we report that
      hepatocyte FGFR substrate 2alpha (FRS2alpha), a scaffold protein essential for
      canonical FGFRs to activate the ERK and AKT pathways, was required for the
      regulation of bile acid production by the FGF15/19-FGFR4 signaling axis. This
      occurred through limiting the extent of increases in Cyp7a1 expression induced by
      prandial activity. Excess FGFR4 kinase activity reduced the amplitude of the
      increase whereas a lack of FGFR4 augmented the increase of Cyp7a1 expression in
      the liver. Ablation of Frs2alpha alleles in hepatocytes abrogated the regulation
      of Cyp7a1 expression by FGFR4. Together, the results demonstrate that FRS2alpha
      mediated pathways are essential for the FGF15/FGF19-FGFR4 signaling axis to
      control bile acid homeostasis. 

PMID- 25056541
TI  - Activation of the liver X receptor inhibits Th17 and Th1 responses in Behcet's
      disease and Vogt-Koyanagi-Harada disease.
AB  - Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome are two intraocular
      inflammatory diseases that are caused by an aberrant T lymphocyte response. Th17
      cells, mainly producing the cytokine IL-17, and Th1 cells, characterized by the
      production of the index cytokine IFN-gamma, are the CD4(+) T lymphocyte subsets
      implicated in the pathogenesis of both BD and VKH. Suppressing the excessive
      response of these Th17 and Th1 cells has been reported to be an effective
      therapeutic approach to treat these patients and continuous efforts are being
      undertaken to find new methods to modulate the function of these cells. Evidence
      is emerging that the Liver X receptor (LXR) is an important regulator of
      inflammatory and immune responses and the study reported here was designed to
      investigate the role of LXR activation in BD and VKH. Here we demonstrate that
      the frequency of Th17 and Th1 cells along with the relevant cytokines IL-17, IFN
      gamma and corresponding transcriptional factors RORC, T-bet were all decreased
      following LXR activation by the agonist GW3965. LXR controlled the expression of
      inflammatory cytokines through an effect on NF-kappa B (NFkappab)
      phosphorylation. Data from our study provide evidence for an association between
      a decreased LXR expression and disease activity in both BD and VKH, due to the
      fact that a lower LXR activation may result in an enhanced Th1 and Th17 immune
      response. Our study suggests that enhancing LXR activation may offer a potential
      therapeutic approach targeting aberrant immune responses by inhibiting Th1 and
      Th17 cell responses. 

PMID- 25056540
TI  - Suppression of NF-kappaB activation by gentian violet promotes osteoblastogenesis
      and suppresses osteoclastogenesis.
AB  - Skeletal mass is regulated by the coordinated action of bone forming osteoblasts
      and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to
      bone formation lead to net bone loss and the development of osteoporosis, a
      devastating disease that predisposes the skeleton to fractures. Bone fractures
      are associated with significant morbidity and in the case of hip fractures, high
      mortality. Gentian violet (GV), a cationic triphenylmethane dye, has long been
      used as an antifungal and antibacterial agent and is presently under
      investigation as a potential chemotherapeutic and antiangiogenic agent. However,
      effects on bone cells have not been previously reported and the mechanisms of
      action of GV, are poorly understood. In this study we show that GV suppresses
      receptor activator of NF-kappaB ligand (RANKL)-induced differentiation of
      RAW264.7 osteoclast precursors into mature osteoclasts, but paradoxically
      stimulates the differentiation of MC3T3 cells into mineralizing osteoblasts.
      These actions stem from the capacity of GV to suppress activation of the nuclear
      factor kappa B (NF-kappaB) signal transduction pathway that is required for
      osteoclastogenesis, but inhibitory to osteoblast differentiation and activity.
      Our data reveal that GV is an inhibitor of NF-kappaB activation and may hold
      promise for modulation of bone turnover to promote a balance between bone
      formation and bone resorption, favorable to gain of bone mass. 

PMID- 25056542
TI  - Calcium and zinc containing bactericidal glass coatings for biomedical metallic
      substrates.
AB  - The present work presents new bactericidal coatings, based on two families of non
      toxic, antimicrobial glasses belonging to B2O3-SiO2-Na2O-ZnO and SiO2-Na2O-Al2O3
      CaO-B2O3 systems. Free of cracking, single layer direct coatings on different
      biomedical metallic substrates (titanium alloy, Nb, Ta, and stainless steel) have
      been developed. Thermal expansion mismatch was adjusted by changing glass
      composition of the glass type, as well as the firing atmosphere (air or Ar)
      according to the biomedical metallic substrates. Formation of bubbles in some of
      the glassy coatings has been rationalized considering the reactions that take
      place at the different metal/coating interfaces. All the obtained coatings were
      proven to be strongly antibacterial versus Escherichia coli (>4 log). 

PMID- 25056543
TI  - BRCA1 EXON 11, a CERES (composite regulatory element of splicing) element
      involved in splice regulation.
AB  - Unclassified variants (UV) of BRCA1 can affect normal pre-mRNA splicing. Here, we
      investigate the UV c.693G>A, a "silent" change in BRCA1 exon 11, which we have
      found induces aberrant splicing in patient carriers and in vitro. Using a
      minigene assay, we show that the UV c.693G>A has a strong effect on the splicing
      isoform ratio of BRCA1. Systematic site-directed mutagenesis of the area
      surrounding the nucleotide position c.693G>A induced variable changes in the
      level of exon 11 inclusion/exclusion in the mRNA, pointing to the presence of a
      complex regulatory element with overlapping enhancer and silencer functions.
      Accordingly, protein binding analysis in the region detected several splicing
      regulatory factors involved, including SRSF1, SRSF6 and SRSF9, suggesting that
      this sequence represents a composite regulatory element of splicing (CERES). 

PMID- 25056544
TI  - Possible prognostic and therapeutic significance of c-Kit expression, mast cell
      count and microvessel density in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is
      increasing worldwide. Tumor angiogenesis is known to play a crucial role in the
      etiopathogenesis of RCC and over the last few years an even deeper knowledge of
      its contribution in metastatic RCC development has led to the development of
      numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib,
      axitinib, tivozanib, and dovitinib). The above agents are principally directed
      against vascular endothelial growth factor receptor (VEGFR) members and also
      against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC
      (ccRCC), the main RCC subtype, is less well established. Whether c-kitR
      activation through its ligand, stem cell factor (SCF) contributes significantly
      to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be
      established. It is important to underscore that the c-KitR is expressed on mast
      cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we
      review here the principal studies that have evaluated c-Kit expression in RCC.
      Moreover, we summarize some investigations that have observed the distribution of
      MCs in primary renal cancer and in adjacent normal tissue with appropriate
      histological immunohistochemical techniques. We also focus on few studies that
      have evaluated the correlation between RCC proliferation, MC count and
      microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of
      this review of the literature is to clarify if c-KitR expression, MC count and
      MVD could have prognostic significance and the possible predictive therapeutic
      implications in RCC. 

PMID- 25056545
TI  - Antioxidant capacities and total phenolic contents enhancement with acute gamma
      irradiation in Curcuma alismatifolia (Zingiberaceae) leaves.
AB  - The present study was conducted in order to assess the effect of various doses of
      acute gamma irradiation (0, 10, 15, and 20 Gy) on the improvement of bioactive
      compounds and their antioxidant properties of Curcuma alismatifolia var. Sweet
      pink. The high performance liquid chromatography (HPLC) and gas chromatography
      (GC) analysis uncovered that various types of phenolic, flavonoid compounds, and
      fatty acids gradually altered in response to radiation doses. On the other hand,
      antioxidant activities determined by 1,1-Diphenyl-2-picryl-hydrazyl (DPPH),
      ferric reduction, antioxidant power (FRAP), and 2,2-azino-bis-3
      ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay showed a
      higher irradiation level significantly increased the antioxidant properties. This
      study revealed an efficient effect of varying levels of gamma radiation, based on
      the pharmaceutical demand to enhance the accumulation and distribution of
      bioactive compounds such as phenolic and flavonoid compounds, fatty acids, as
      well as their antioxidant activities in the leaves of C. alismatifolia var. Sweet
      pink. 

PMID- 25056546
TI  - Effects of the novel compound DK223 ([1E,2E-1,2-Bis(6-methoxy-2H-chromen-3
      yl)methylene]hydrazine) on migration and proliferation of human keratinocytes and
      primary dermal fibroblasts.
AB  - Wound healing plays an important role in protecting the human body from external
      infection. Cell migration and proliferation of keratinocytes and dermal
      fibroblasts are essential for proper wound healing. Recently, several studies
      have demonstrated that secondary compounds produced in plants could affect skin
      cells migration and proliferation. In this study, we identified a novel compound
      DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) that
      concomitantly induced human keratinocyte migration and dermal fibroblast
      proliferation. We evaluated the regulation of epithelial and mesenchymal protein
      markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as
      extracellular matrix (ECM) secretion and metalloproteinase families in dermal
      fibroblasts. DK223 upregulated keratinocyte migration and significantly increased
      the epithelial marker E-cadherin in a time-dependent manner. We also found that
      reactive oxygen species (ROS) increased significantly in keratinocytes after 2 h
      of DK223 exposure, returning to normal levels after 24 h, which indicated that
      DK223 had an early shock effect on ROS production. DK223 also stimulated
      fibroblast proliferation, and induced significant secretion of ECM proteins, such
      as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment
      induced TGF-beta1, which is involved in a signaling pathway that mediates
      proliferation. In conclusion, DK223 simultaneously induced both keratinocyte
      migration via ROS production and fibroblast proliferation via TGF-beta1
      induction. 

PMID- 25056547
TI  - DNA break mapping reveals topoisomerase II activity genome-wide.
AB  - Genomic DNA is under constant assault by endogenous and exogenous DNA damaging
      agents. DNA breakage can represent a major threat to genome integrity but can
      also be necessary for genome function. Here we present approaches to map DNA
      double-strand breaks (DSBs) and single-strand breaks (SSBs) at the genome-wide
      scale by two methods called DSB- and SSB-Seq, respectively. We tested these
      methods in human colon cancer cells and validated the results using the
      Topoisomerase II (Top2)-poisoning agent etoposide (ETO). Our results show that
      the combination of ETO treatment with break-mapping techniques is a powerful
      method to elaborate the pattern of Top2 enzymatic activity across the genome. 

PMID- 25056549
TI  - Umbilical metastasis derived from breast cancer: report of a case.
AB  - Umbilical metastases mainly arise from malignancies of the digestive and
      gynecological systems, but rarely from breast cancer. A 64-year-old woman with a
      history of breast cancer was referred to us for investigation of a painful lesion
      in the umbilicus. Immunohistochemical staining of a specimen obtained by biopsy
      from the nodule showed umbilical metastasis of breast cancer. After a work up,
      she was successfully treated with a combination of surgery and endocrine therapy.
      We report this case to reinforce that not all periumbilical tumoral deposits are
      consistent. 

PMID- 25056548
TI  - Crosslinking liposomes/cells using cholesteryl group-modified tilapia gelatin.
AB  - Cholesteryl group-modified tilapia gelatins (Chol-T-Gltns) with various Chol
      contents from 3 to 69 mol % per amino group of Gltn were prepared for the
      assembly of liposomes and cells. Liposomes were physically crosslinked by
      anchoring Chol groups of Chol-T-Gltns into lipid membranes. The resulting
      liposome gels were enzymatically degraded by addition of collagenase. Liposome
      gels prepared using Chol-T-Gltn with high Chol content (69Chol-T-Gltn) showed
      slower enzymatic degradation when compared with gels prepared using Chol-T-Gltn
      with low Chol content (3Chol-T-Gltn). The hepatocyte cell line HepG2 showed good
      assembly properties and no cytotoxic effects after addition of 69Chol-T-Gltns. In
      addition, the number of HepG2 cells increased with concentration of 69Chol-T
      Gltns. Therefore, Chol-T-Gltn, particularly, 69Chol-T-Gltn, can be used as an
      assembling material for liposomes and various cell types. The resulting
      organization can be applied to various biomedical fields, such as drug delivery
      systems, tissue engineering and regenerative medicine. 

PMID- 25056550
TI  - Dynamic contrast-enhanced MR imaging of endometrial cancer: optimizing the
      imaging delay for tumour-myometrium contrast.
AB  - PURPOSE: To investigate the optimal imaging delay time of dynamic contrast
      enhanced magnetic resonance (MR) imaging in women with endometrial cancer.
      MATERIALS AND METHODS: This prospective single-institution study was approved by
      the institutional review board, and informed consent was obtained from the
      participants. Thirty-five women (mean age, 54 years; age range, 29-66 years)
      underwent dynamic contrast-enhanced MR imaging with a temporal resolution of 25
      40 seconds. The signal intensity difference ratios between the myometrium and
      endometrial cancer were analyzed to investigate the optimal imaging delay time
      using single change-point analysis. RESULTS: The optimal imaging delay time for
      appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The
      median optimal imaging delay time was 91.3 seconds, with an interquartile range
      of 46.2 to 119.5 seconds. The median signal intensity difference ratios between
      the myometrium and endometrial cancer were 0.03, with an interquartile range of 
      0.01 to 0.06, on the pre-contrast MR imaging and 0.20, with an interquartile
      range of 0.15 to 0.25, on the post-contrast MR imaging. CONCLUSION: An imaging
      delay of approximately 90 seconds after initiating contrast material injection
      may be optimal for obtaining appropriate tumour-myometrium contrast in women with
      endometrial cancer. KEY POINTS: * Recent advances have allowed for MR imaging of
      high temporal resolution. * Contrast-enhanced MR imaging is helpful for
      evaluation of endometrial cancer. * An imaging delay of 90 seconds may be
      optimal.

PMID- 25056552
TI  - What's your diagnosis? Happy Halloween!

PMID- 25056551
TI  - Unstable osteochondral fragment of the lateral femoral condyle containing the
      popliteus tendon origin. Report of three cases.
AB  - We report a series of three cases of unusual locations of chronic osteochondral
      fragments arising from the posterolateral aspect of the lateral femoral condyle,
      presenting acutely in young adults, in which the unstable fragment contained the
      origin of the popliteus tendon, with MRI and arthroscopic correlation. Although
      atypical, we hypothesize that these cases represent adult osteochondritis
      dissecans with extension to a popliteus tendon origin. Preoperative diagnosis of
      popliteus tendon involvement may influence clinical management in patients with
      an unstable osteochondral fragment in this location. 

PMID- 25056553
TI  - Design and preparation of ethynyl-pyrene modified platinum-acetylide gelators and
      their application in dispersion of graphene.
AB  - A series of new ethynyl-pyrene modified platinum-acetylide gelators were
      prepared, some of which were found to be able to incorporate graphene into the
      metallogel matrix. 

PMID- 25056554
TI  - Effects of heat treatment and moisture contents on interactions between lauric
      acid and starch granules.
AB  - This study aimed to understand the effects of the moisture content of granular
      normal cornstarch (NC), heat treatment at 80  degrees C, and order of adding
      lauric acid (LA) to starch before or after the heat treatment on the
      physicochemical properties and digestibility of the starch. LA was added to NC
      priority heated with different moisture contents (10, 20, 30, 40, and 50%) or
      added to dried NC and then heated with different moisture contents. The
      hydrothermal/LA treatments increased the pasting temperature but decreased the
      peak viscosity of the NC. Light and scanning electron microscopy revealed that
      the addition of LA retarded gelatinization. The hydrothermal/LA treatments
      changed the X-ray pattern of the NC to a mixture of A- and V-type patterns. The
      thermal property and digestibility analysis showed that 40% was the optimum
      moisture content for the formation of the amylose-LA complex and adding LA prior
      to heating the NC favored the formation of slowly digestible starch. 

PMID- 25056555
TI  - Real-time ultrasound and freehand-SPECT. Experiences with sentinel lymph node
      mapping.
AB  - Aim of this work is to report first experiences of the feasibility and
      applicability of a hybrid freehandSPECT/ultrasound (fh-SPECT/US) imaging concept,
      with regard to SLN imaging, in patients with breast cancer and malignant
      melanoma. PATIENTS, METHODS: 18 patients with breast cancer or malignant melanoma
      received standard SLN scintigraphy. Following this, fh-SPECT using
      declipse(r)SPECT (SurgicEye, Munich, Germany) was performed, a handheld-gamma
      camera-based method to visualize activity distribution within a region of
      interest as a cross-sectional data set. These data were transferred to an
      ultrasound device and sensor-navigated ultrasound was performed combining fh
      SPECT data with ultrasound images, displaying superimposed images. Quality of fh
      SPECT and co-registration accuracy was assigned to one of four categories and
      occurrence of artefacts was assessed. RESULTS: In 4/18 examinations, there was a
      no deviation regarding co-registration of both data sets. For 9/18 patients,
      there was a deviation of <1 cm (mean 0.7+/-0.3 cm, range 0.3-1.0 cm). For 3/18
      patients, a deviation >1 cm was present (mean 1.7+/-0.3 cm, range 1.5-2.0 cm). In
      2/18 examinations no lymph node was found in the region of highest activity. Fh
      SPECT reconstruction artifacts occurred in 6/18 examinations. CONCLUSION: The
      fusion imaging concept combining SLN information with ultrasound images presented
      here proves to be feasible and technically successful. However, significant
      technical limitations were shown in fh-SPECT quality and fusion precision.
      Subject to technical optimisation of SPECT quality and co-registration, a
      meaningful contribution to the preoperative planning of lymph node therapy is
      imaginable. Thus, fundamentally a preoperative histological examination by fh
      SPECT/US-guided biopsy is possible.

PMID- 25056556
TI  - Sleep and vigilance linked to melanism in wild barn owls.
AB  - Understanding the function of variation in sleep requires studies in the natural
      ecological conditions in which sleep evolved. Sleep has an impact on individual
      performance and hence may integrate the costs and benefits of investing in
      processes that are sensitive to sleep, such as immunity or coping with stress.
      Because dark and pale melanic animals differentially regulate energy homeostasis,
      immunity and stress hormone levels, the amount and/or organization of sleep may
      covary with melanin-based colour. We show here that wild, cross-fostered nestling
      barn owls (Tyto alba) born from mothers displaying more black spots had shorter
      non-REM (rapid eye movement) sleep bouts, a shorter latency until the occurrence
      of REM sleep after a bout of wakefulness and more wakefulness bouts. In male
      nestlings, the same sleep traits also correlated with their own level of
      spotting. Because heavily spotted male nestlings and the offspring of heavily
      spotted biological mothers switched sleep-wakefulness states more frequently, we
      propose the hypothesis that they could be also behaviourally more vigilant.
      Accordingly, nestlings from mothers displaying many black spots looked more often
      towards the nest entrance where their parents bring food and towards their
      sibling against whom they compete. Owlets from heavily spotted mothers might
      invest more in vigilance, thereby possibly increasing associated costs due to
      sleep fragmentation. We conclude that different strategies of the regulation of
      brain activity have evolved and are correlated with melanin-based coloration. 

PMID- 25056557
TI  - Healthcare worker influenza vaccination in Oregon nursing homes: correlates of
      facility characteristics.
AB  - OBJECTIVES: Nursing home (NH) employee influenza vaccination is associated with
      reductions in morbidity and mortality among residents. Little is known regarding
      associations between NH characteristics and employee influenza vaccination rates
      (EVRs). This study identifies NH characteristics that may be associated with
      EVRs. DESIGN: Data on employee vaccination rates and programs were gathered from
      the Office for Oregon Health Policy and Research reports for 3 influenza seasons
      from 2009 to 2012 and merged with Online Survey, Certification, and Reporting
      files, from which facility characteristics were obtained. Market controls were
      obtained from the 2010 Area Health Resource File. Multivariate linear and
      logistic regression were used to model relationships between facility
      characteristics and EVR per facility per year, whether formal education for
      employees was conducted, and whether 2010, 2015, and 2020 Healthy People targets
      were met. SETTING: Oregon nursing homes from 2009 to 2012. PARTICIPANTS: NHs
      reporting sufficient data to calculate an EVR were included. Based on information
      obtained from 2009-2010, 2010-2011, and 2011-2012 surveys, EVRs were calculated
      for 113/140, 129/141, and 137/140 (81%, 91%, and 98% of) NHs, respectively.
      MEASUREMENTS: Dependent variables were EVR per facility per year, whether formal
      education for employees was conducted, and whether 2010, 2015, and 2020 Healthy
      People targets were met. Independent variables included facility characteristics
      and market controls. RESULTS: On average, chain-affiliated NHs had 9% higher EVRs
      (P = .01) and 73% higher odds of achieving 60% EVR (2010 target, P = .05) than
      free-standing NHs. For-profit NHs had, on average, 8% lower EVRs (P = .04) than
      not-for-profit NHs. Surprisingly, a 10% increase in proportion of Medicaid
      residents was associated with a 2% increase in EVR (P = .01) and higher odds of
      achieving 60% (odds ratio = 1.20, P = .004) and 70% (2015 target, odds ratio =
      1.14, P = .05) EVR. CONCLUSION: Given that NHs generally have low employee
      influenza vaccination rates, it may be necessary to target low-performing
      facilities to achieve substantial improvements. However, significant correlates
      of this study cannot be easily addressed by NH management or policymakers.
      Without policy change encouraging key components of vaccination programs, public
      reporting may be insufficient to improve EVRs.

PMID- 25056558
TI  - Galectin Hco-gal-m from Haemonchus contortus modulates goat monocytes and T cell
      function in different patterns.
AB  - BACKGROUND: Monocytes and T cells are two major subpopulations of peripheral
      blood mononuclear cells (PBMC) and play an essential role in the innate and
      adaptive immune systems. Different members of the galectin family show multiple
      and distinct regulatory effects on different cell types. Previous studies have
      demonstrated that the galectin from Haemonchus contortus (Hco-gal-m) performed
      immunomodulatory effects on goat PBMC, however, which subpopulation of PBMC is
      the primary target of Hco-gal-m and whether the immune modulations share the same
      mechanism remain unclear. METHODS: In this study, the developmental expression of
      Hco-gal-m was analyzed by RT-PCR and Western blot analysis. The distribution of
      Hco-gal-m in adult worm was detected by an immunohistochemical test. The binding
      activity of the recombinant Hco-gal-m (rHco-gal-m) on goat monocytes and T cells
      were assessed by flow cytometry. The immunomodulatory effects of Hco-gal-m on
      cytokine secretion, cell activation and apoptosis were observed by co-incubation
      of rHco-gal-m with goat monocytes and T cells. RESULTS: Hco-gal-m was expressed
      in L4 as well as adult worms and predominantly localized at the internal surface
      of the worm guts. rHco-gal-m could bind to both monocytes and T cells. The
      engagement of rHco-gal-m decreased the production of IL-6, IL-10 and TNF-alpha in
      T cells, however, it significantly increased the secretion of IL-10 in monocytes.
      After rHco-gal-m exposure, the expression of MHC-II on monocytes and that of CD25
      on T cells were restricted. Consequently, T cell proliferations were potently
      inhibited by rHco-gal-m. In addition, rHco-gal-m induced apoptosis in T cells,
      but not significantly in monocytes. CONCLUSIONS: Our results indicated that rHco
      gal-m modulated goat monocytes and T cell function in different patterns.

PMID- 25056559
TI  - Ritual uses of palms in traditional medicine in sub-Saharan Africa: a review.
AB  - Palms (Arecaceae) are prominent elements in African traditional medicines. It is,
      however, a challenge to find detailed information on the ritual use of palms,
      which are an inextricable part of African medicinal and spiritual systems. This
      work reviews ritual uses of palms within African ethnomedicine. We studied over
      200 publications on uses of African palms and found information about ritual uses
      in 26 of them. At least 12 palm species in sub-Saharan Africa are involved in
      various ritual practices: Borassus aethiopum, Cocos nucifera, Dypsis
      canaliculata, D. fibrosa, D. pinnatifrons, Elaeis guineensis, Hyphaene coriacea,
      H. petersiana, Phoenix reclinata, Raphia farinifera, R. hookeri, and R. vinifera.
      In some rituals, palms play a central role as sacred objects, for example the
      seeds accompany oracles and palm leaves are used in offerings. In other cases,
      palms are added as a support to other powerful ingredients, for example palm oil
      used as a medium to blend and make coherent the healing mixture. A better
      understanding of the cultural context of medicinal use of palms is needed in
      order to obtain a more accurate and complete insight into palm-based traditional
      medicines. 

PMID- 25056560
TI  - Through-space conjugated molecular wire comprising three pi-electron systems.
AB  - A [2.2]paracyclophane-based through-space conjugated oligomer comprising three pi
      electron systems was designed and synthesized. The arrangement of three pi
      conjugated systems in an appropriate order according to the energy band gap
      resulted in efficient unidirectional photoexcited energy transfer by the Forster
      mechanism. The energy transfer efficiency and rate constants were estimated to be
      >0.999 and >10(12) s(-1), respectively. The key point for the efficient energy
      transfer is the orientation of the transition dipole moments. The time-dependent
      density functional theory (TD-DFT) studies revealed the transition dipole moments
      of each stacked pi-electron system; each dipole moment was located on the long
      axis of each stacked pi-electron system. This alignment of the dipole moments is
      favorable for fluorescence resonance energy transfer (FRET).

PMID- 25056561
TI  - Identification of the protopanaxatriol synthase gene CYP6H for ginsenoside
      biosynthesis in Panax quinquefolius.
AB  - Panax quinquefolius is one of perennial herbs and well known for its outstanding
      pharmacological activity. Ginsenosides are thought to be the main active
      ingredients in P. quinquefolius and exist in many kinds of plant genus Panax
      (ginseng). Protopanaxatriol synthase, which is considered cytochrome P450
      (CYP450) in ginsenoside biosynthesis pathway can convert protopanaxadiol into
      protopanaxatriol. However, the protopanaxatriol synthase gene in P. quinquefolius
      has not been identified. Here, we cloned and identified a protopanaxatriol
      synthase gene from P. quinquefolius (CYP6H, GenBank accession no. KC190491) at
      the first time, reverse transcription-PCR (RT-PCR) analysis showed no obvious
      transcription change of CYP6H in methyl jasmonate (MeJA)-induced hairy roots.
      Ectopic expression of CYP6H in Saccharomyces cerevisiae resulted in the
      production of protopanaxatriol with added exogenous protopanaxadiol and confirmed
      by liquid chromatography-atmospheric pressure chemical ionization mass
      spectrometry (LC/APCIMS). Moreover, high-performance liquid chromatography (HPLC)
      analysis shows that RNA interferences of CYP6H in transgenic hairy roots could
      increase the accumulation of protopanaxadiol-type ginsenosides and decrease the
      accumulation of protopanaxatriol-type ginsenosides, whereas the effect of
      overexpression CYP6H in transgenic hairy roots was contrary. Our study indicated
      that CYP6H is a gene encoding protopanaxadiol 6-hydroxylase which could convert
      protopanaxadiol into protopanaxatriol in P. quinquefolius ginsenoside
      biosynthesis, we also have confirmed the function of CYP6H on effect accumulation
      of ginsenosides. 

PMID- 25056562
TI  - [Injuries of the acromioclavicular joint in athletes].
AB  - Acromioclavicular joint (ACJ) dislocation is a common injury to the shoulder
      girdle, especially in contact and high velocity sports. Besides the severity of
      the injury, and particularly in competitive and elite athletes and the type of
      sports, individual career plans and in and out of season injuries have to be
      taken into account when advising treatment for athletes. Conservative treatment
      is reserved for low-grade dislocations and in-season athletes. The aim is fast
      pain relief and a safe return to competitive sport. High-grade ACJ dislocations
      in athletes should be treated surgically. Arthroscopic and arthroscopically
      assisted techniques can offer a lower risk of infection, a higher patient
      acceptance in terms of cosmetic perspectives and the potential to treat
      concomitant glenohumeral lesions and may avoid potential disadvantages of open
      techniques, such as secondary obligatory implant removal and extensive soft
      tissue preparation with a relevant approach morbidity. 

PMID- 25056563
TI  - [Late complication after Roux-en-Y gastric bypass: Unusual finding].

PMID- 25056564
TI  - [Necessity of a structured postoperative surveillance after pancreatic resection
      for intraductal papillary mucinous neoplasms].

PMID- 25056565
TI  - Discrete nanoparticles of ruta graveolens induces the bacterial and fungal
      biofilm inhibition.
AB  - Ruta graveolens silver nanoparticles (AgNPs) showed the color change within 30
      min and characterized using UV-visible spectra, Fourier Transform Infrared
      (FTIR), X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). UV
      visible spectrum of R. graveolens AgNPs showed the sharp peak at the wavelength
      of 440-560 nm. XRD patterns confirmed that crystalline nature of R. graveolens
      AgNPs and FTIR results revealed that phytochemical reaction of these R.
      graveolens is responsible for the synthesis of AgNPs. TEM results showed the size
      of the R. graveolens AgNPs around 30-50 nm with spherical and triangular nature.
      Further, the antibacterial and antibiofilm activity of R. graveolens AgNPs showed
      the effective inhibitory activity against clinically important Staphylococcus
      aureus, Pseudomonas aeruginosa and Candida albicans. Our findings suggest that R.
      graveolens AgNPs can be exploited toward the development of potential
      antibacterial agents for various biomedical and environmental applications.

PMID- 25056566
TI  - Morphological control and evolution of octahedral and truncated trisoctahedral Pt
      Au alloy nanocrystals under microwave irradiation.
AB  - Uniform and well-defined truncated trisoctahedral and octahedral Pt-Au alloy
      nanocrystals were fabricated by co-reducing H(2)PtC(l6)-HAuC(l4) with
      tetraethylene glycol (TEG) under microwave irradiation for only 140 s. Iodide
      ions were critical to the morphological control and evolution of Pt-Au alloy
      nanostructures. The as-prepared Pt-Au alloy nanocrystals exhibited efficient
      electrocatalytic activities.

PMID- 25056567
TI  - Effect of extended-release dexmethylphenidate and mixed amphetamine salts on
      sleep: a double-blind, randomized, crossover study in youth with attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: We sought to determine the dose-response effects of extended-release
      (ER) dexmethylphenidate (d-MPH) and ER mixed amphetamine salts (MAS) on objective
      measures of sleep. METHODS: This was an 8-week, double-blind, placebo-controlled,
      randomized, two period, crossover study of youth with attention-deficit
      hyperactivity disorder (ADHD) as confirmed by the Kiddie Schedule for Affective
      Disorders for School-Age Children-Present and Lifetime version (K-SADS-PL).
      Children aged 10-17 years were recruited from clinical practice, colleague
      referrals, and flyers. Participants were randomized to initially receive either d
      MPH or MAS. During each 4-week drug period, children received three dose levels
      (10, 20, and 25/30 mg) in ascending order, with placebo substituted for active
      medication in a randomized fashion during 1 week of the study. After 4 weeks,
      participants were switched to the alternative medication for another 4 weeks of
      treatment. The main outcome measure was sleep duration as measured by actigraphy.
      Children, parents, and researchers were blinded to drug, dose, and placebo
      status. RESULTS: Sixty-five participants met the inclusion criteria and were
      enrolled in the study. Of these, 37 participants with sufficient sleep data for
      analysis were included. Sleep schedule measures showed a significant effect for
      dose on sleep start time (F(1,36) = 6.284; p < 0.05), with a significantly later
      sleep start time when children were receiving 20- or 30-mg doses, compared with
      placebo (p < 0.05). A significant dose effect was found on actual sleep duration
      (F(1,36) = 8.112; p < 0.05), with significantly shorter actual sleep duration for
      subjects receiving 30 mg compared with those receiving placebo (p < 0.05). There
      were no significant differences on sleep duration or sleep schedule between the
      two stimulant medications. The trial is complete and closed to follow-up.
      CONCLUSIONS: Higher stimulant doses were associated with reduced sleep duration
      and later sleep start times, regardless of medication class. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00393042.

PMID- 25056568
TI  - Off-label prescribing of antiepileptic drugs in pharmacoresistant epilepsy: a
      cross-sectional drug utilization study of tertiary care centers in Italy.
AB  - PURPOSE: To assess the extent of off-label prescribing of antiepileptic drugs
      (AEDs) and associated variables in a large population of patients with
      pharmacoresistant epilepsy. METHODS: Descriptive analysis of data recorded from
      consecutively enrolled patients with pharmacoresistant epilepsy attending 11
      tertiary referral centers in Italy. Off-label use was stratified by therapeutic
      indication, dose, and age. Multivariate logistic regression was used to identify
      variables associated with off-label prescription. RESULTS: Of a total of 1,124
      patients enrolled between November 2006 and August 2007, 53 % (101/191) of
      children and 31 % (287/933) of adults were receiving at least one off-label AED
      prescription. Among adults, off-label use was related primarily to indication and
      was highest for clobazam (100 %) and ethosuximide (40 %), followed by lamotrigine
      (25 %), and vigabatrin (25 %). In children, clobazam (100 %), lamotrigine (79 %),
      vigabatrin (55 %), ethosuximide (46 %), and levetiracetam (43 %) were most
      frequently used off-label, with indication or age being the main causes depending
      on the specific AED. Logistic regression analysis indicated that higher rates of
      off-label use were associated with a polytherapy regimen (odds ratio [OR] 2.50,
      95 % confidence interval [95 % CI], 1.55-4.03), pediatric age (2.49, 1.66-3.76),
      having failed >=3 AEDs (2.16, 1.04-4.48), a diagnosis of generalized epilepsy
      with structural/metabolic or unknown etiology (2.97, 1.25-7.04), and increasing
      seizure frequency (1.07, 1.01-1.14). CONCLUSIONS: Off-label prescribing of AEDs
      is common among patients with pharmacoresistant epilepsy and is influenced by
      demographic and disease-related characteristics. Studies are needed to improve
      the quality of evidence guiding epilepsy treatment, and to evaluate the risks and
      benefits of off-label prescribing in epilepsy.

PMID- 25056569
TI  - Broad-spectrum micronutrient treatment for attention-deficit/hyperactivity
      disorder: rationale and evidence to date.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric illness,
      which often co-occurs with other common psychiatric problems. Although empirical
      evidence supports the short-term efficacy of pharmacological and behavioural
      treatments, families often search for alternative treatment methods because of
      concerns about side effects and safety, cost and access, as well as fears about
      long-term exposure to psychotropic medications. This review presents the
      published evidence on use of broad-spectrum micronutrients to treat ADHD
      symptoms. This approach makes physiological sense in that nutrients are required
      for many critical biochemical reactions to occur, ranging from manufacturing
      neurotransmitters, to providing the mitochondria with essential nutrients for
      energy production, to assisting the gut to heal from inflammation. Multi-nutrient
      treatment approaches are an intriguing yet under-researched area; all but one of
      the trials conducted in the last decade have shown benefit for the treatment of
      ADHD symptoms, and the one negative trial likely used doses too low to effect
      change. However, the methodologies have varied widely from case-controlled
      studies to open-label trials to one randomized controlled trial. Sample sizes
      have typically been modest, although the effect sizes have tended to be medium to
      large. What is required now is replication, as well as investigation into the
      optimal ingredient range and optimal doses of nutrients. We discuss the proven
      and potential benefits of the broad-spectrum nutrient approach, considering the
      heterogeneous nature of ADHD. 

PMID- 25056570
TI  - Is the presence of varicocele associated with static and dynamic components of
      benign prostatic hyperplasia/lower urinary tract symptoms in elderly men?
AB  - OBJECTIVES: To evaluate the relationship between varicocele and benign prostatic
      hyperplasia/lower urinary tract symptoms in patients over the age of 40 years.
      METHODS: A total of 1040 patients with benign prostatic hyperplasia/lower urinary
      tract symptoms were evaluated for prostate volume, testicular volume, testicular
      consistency, total testosterone, total prostate-specific antigen and body mass
      index. A questionnaire including International Prostate Symptom Score and a
      uroflow test were also carried out. The presence and grade of varicocele was
      determined in each patient by physical examination. RESULTS: Varicocele was found
      bilaterally in 22.3% and unilaterally in 25.7% of the patients. There was no
      difference in terms of age and body mass index distribution between subgroups.
      When grouping patients for varicocele laterality, total testosterone (P = 0.04),
      prostate volume (P = 0.009) and total prostate-specific antigen (P = 0.02) level
      were significantly different. Similarly, these parameters were significant
      between patients with grade 1, 2 and 3 varicocele. Total testosterone level (P =
      0.02) and prostate volume (P = 0.035) were found to be significantly different
      when patients were grouped according to testicular size. A positive correlation
      was found between testosterone level and prostate volume (P = 0.004; r(2) =
      0.084). CONCLUSIONS: Bilateral and/or higher-grade varicocele is associated with
      lower prostate volume and testosterone levels, as well as lower prostate-specific
      antigen levels. However, it is not associated with dynamic components of benign
      prostatic hyperplasia/lower urinary tract symptoms in patients over the age of 40
      years.

PMID- 25056571
TI  - Methaemoglobin and COHb in patients with malaria.
AB  - BACKGROUND: Haemolytic conditions may contribute to disease pathogenesis and
      severe clinical manifestations through the liberation of free haemoglobin (Hb)
      and production of toxic free haem. Thus, free Hb and haem should be associated
      with altered MetHb and COHb levels in malaria as in other conditions. METHODS:
      This study comprises data collected at three different sites: (i) a retrospective
      analysis of the first arterial blood gas result (ABGS) of any patient during 2010
      at the University Hospital in Lisbon; (ii) a retrospective analysis of ABGS from
      patients with severe malaria admitted to the intensive care unit in Berlin,
      Germany; and (iii) a prospective study of non-invasive MetHb measurements in
      children with and without malaria in Lambarene, Gabon. RESULTS: In Lisbon, the
      mean MetHb level was 1.4% (SD: 0.5) in a total of 17,834 ABGS. Only 11 of 98
      samples with a MetHb level of >3.0 referred to infections. COHb levels showed no
      particular association with clinical conditions, including sepsis. In 13 patients
      with severe malaria in Berlin, the mean MetHb levels on admission was 1.29%, with
      1.36% for cerebral malaria and 1.14% for non-cerebral malaria (P > 0.05). All
      COHb measurements were below 2.3%. In Lambarene, Gabon, 132 healthy children had
      a mean MetHb level of 1.57%, as compared to 150 children with malaria, with a
      value of 1.77% and 2.05% in uncomplicated and complicated cases, respectively (P
      < 0.01). CONCLUSIONS: The data appears consistent with the methaemoglobin/haem
      hypothesis in malaria and sepsis pathogenesis. However, although MetHb was
      significantly different between healthy controls and children with malaria in
      Africa, the difference was rather small, also when compared to previous studies.
      Still, non-invasive bedside MetHb testing may warrant further evaluation as it
      could be a simple adjuvant tool for prognosis in resource poor settings.

PMID- 25056572
TI  - The Dopaminergic Midbrain Encodes the Expected Certainty about Desired Outcomes.
AB  - Dopamine plays a key role in learning; however, its exact function in decision
      making and choice remains unclear. Recently, we proposed a generic model based on
      active (Bayesian) inference wherein dopamine encodes the precision of beliefs
      about optimal policies. Put simply, dopamine discharges reflect the confidence
      that a chosen policy will lead to desired outcomes. We designed a novel task to
      test this hypothesis, where subjects played a "limited offer" game in a
      functional magnetic resonance imaging experiment. Subjects had to decide how long
      to wait for a high offer before accepting a low offer, with the risk of losing
      everything if they waited too long. Bayesian model comparison showed that
      behavior strongly supported active inference, based on surprise minimization,
      over classical utility maximization schemes. Furthermore, midbrain activity,
      encompassing dopamine projection neurons, was accurately predicted by trial-by
      trial variations in model-based estimates of precision. Our findings demonstrate
      that human subjects infer both optimal policies and the precision of those
      inferences, and thus support the notion that humans perform hierarchical
      probabilistic Bayesian inference. In other words, subjects have to infer both
      what they should do as well as how confident they are in their choices, where
      confidence may be encoded by dopaminergic firing. 

PMID- 25056573
TI  - Abnormal Neural Activation to Faces in the Parents of Children with Autism.
AB  - Parents of children with an autism spectrum disorder (ASD) show subtle deficits
      in aspects of social behavior and face processing, which resemble those seen in
      ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal
      activation in ASD has been reported in several brain structures linked to social
      cognition, little is known regarding patterns in the BAP. We compared autism
      parents with control parents with no family history of ASD using 2 well-validated
      face-processing tasks. Results indicated increased activation in the autism
      parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face
      processing regions. Exploratory analyses revealed hyper-activation of lateral
      occipital cortex (LOC) bilaterally in autism parents with aloof personality
      ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to
      underlying genetic liability for ASD, whereas abnormalities in the LOC and right
      FG are more specific to behavioral features of the BAP. Results extend our
      knowledge of neural circuitry underlying abnormal face processing beyond those
      previously reported in ASD to individuals with shared genetic liability for
      autism and a subset of genetically related individuals with the BAP. 

PMID- 25056574
TI  - Nestin positively regulates the Wnt/beta-catenin pathway and the proliferation,
      survival and invasiveness of breast cancer stem cells.
AB  - INTRODUCTION: We investigated Nestin expression in triple-negative breast cancer
      and examined how the modulation of Nestin expression affects cell cycle
      progression, survival, invasion and regulatory signaling in breast cancer stem
      cells (CSC) in vitro. METHODS: Nestin expression in 150 triple-negative breast
      cancer specimens were examined by immunohistochemistry. The role of Nestin
      expression in tumorigenesis was examined by assaying naturally occurring
      Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26
      clinical specimens, where Nestin overexpression and silencing was achieved by
      genetic manipulation, for their ability to form mammospheres and induce solid
      tumors. Cell cycle progression, spontaneous apoptosis and invasiveness of Nestin
      silenced breast CSC were investigated by flow cytometry and transwell assays. The
      relative levels of expression of epithelial-mesenchymal transition (EMT) and
      Wnt/beta-catenin pathway-related molecules were determined by western blotting.
      RESULTS: Nestin expression was significantly associated with poor survival in
      patients with triple-negative breast cancer (P = 0.01). Nestinhigh breast CSC
      rapidly formed typical mammospheres in vitro. Nestinhigh, but not Nestinlow CSC,
      efficiently formed solid tumors in vivo. Nestin silencing induced cell cycle
      arrest at G2/M (52.03% versus 19.99% in controls) and promoted apoptosis (36.45%
      versus 8.29% in controls). Nestin silencing also inhibited breast CSC
      invasiveness, and was associated with significantly upregulated E-cadherin, while
      N-cadherin, vimentin, a-smooth muscle actin (a-SMA), matrix metalloproteinase-2
      (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression was
      downregulated (P <0.05 for all). Nestin silencing also upregulated Axin, glycogen
      synthase kinase-3 beta (GSK-3beta), adenomatous polyposis coli (APC), and
      peroxisome proliferator-activated receptor alpha (PPARa), and downregulated beta
      catenin, c-Myc, cyclin D and MMP-7 expression in CSC. Inhibition of the Wnt/beta
      catenin pathway mitigated mammosphere formation in Nestinhigh CSC, while
      inhibition of GSK-3beta promoted the mammosphere formation in Nestinlow CSC (P
      <0.05 for all). CONCLUSIONS: Our data indicates that Nestin positively regulates
      the proliferation, survival and invasiveness of breast CSC by enhancing Wnt/beta
      catenin activation.

PMID- 25056575
TI  - Establishment of ATP-based luciferase viability assay in 96-well plate for
      Trypanosoma congolense.
AB  - Animal African trypanosomosis (AAT), caused by Trypanosoma congolense, is
      widespread throughout sub-Saharan Africa. There are significant concerns related
      to the current drugs available for the treatment of AAT due to their limited
      effectiveness across species and their adverse effects. Moreover, drug resistant
      trypanosomes have recently been reported in the field. High throughput screening
      (HTS) of large chemical compound library collections is a promising approach for
      identifying novel drug candidates. While HTS for Trypanozoon trypanosomes, T.
      brucei sspp. and T. evansi is well established, no assays have been developed for
      T. congolense. In the present study, the authors developed an ATP-based
      luciferase viability assay for T. congolense in a 96-well plate format. The
      calculated 50% inhibitory concentration (IC50) values for pentamidine and
      diminazene were 10-100 times higher in T. congolense than in T. brucei. This
      result suggests that the transporters for the 2 tested compounds differ between
      T. congolense and T. brucei. This assay could further be applied to screen novel
      chemical compounds for the treatment of AAT caused by T. congolense. 

PMID- 25056576
TI  - Variations in epithelial Na(+) transport and epithelial sodium channel
      localisation in the vaginal cul-de-sac of the brushtail possum, Trichosurus
      vulpecula, during the oestrous cycle.
AB  - The fluid in the vaginal cul-de-sac of the brushtail possum, Trichosurus
      vulpecula, is copious at ovulation when it may be involved in sperm transport or
      maturation, but is rapidly reabsorbed following ovulation. We have used the
      Ussing short-circuit current (Isc) technique and measurements of transcript and
      protein expression of the epithelial Na(+) channel (ENaC) to determine if
      variations in electrogenic Na(+) transport are associated with this fluid
      absorption. Spontaneous Isc (<20uAcm(-2) during anoestrus, 60-80uAcm(-2) in
      cycling animals) was inhibited by serosal ouabain. Mucosal amiloride (10umolL(
      1)), an inhibitor of ENaC, had little effect on follicular Isc but reduced luteal
      Isc by ~35%. This amiloride-sensitive Isc was dependent on mucosal Na(+) and the
      half-maximal inhibitory concentration (IC50)-amiloride (0.95MUmolL(-1)) was
      consistent with ENaC-mediated Na(+) absorption. Results from polymerase chain
      reaction with reverse transcription (RT-PCR) indicate that alphaENaC mRNA is
      expressed in anoestrous, follicular and luteal phases. However, in follicular
      animals alphaENaC immunoreactivity in epithelial cells was distributed throughout
      the cytoplasm, whereas immunoreactivity was restricted to the apical pole of
      cells from luteal animals. These data suggest that increased Na(+) absorption
      contributes to fluid absorption during the luteal phase and is regulated by
      insertion of ENaC into the apical membrane of cul-de-sac epithelial cells. 

PMID- 25056578
TI  - Executive Function Differences Between Bilingual Arabic-English and Monolingual
      Arabic Children.
AB  - This study aimed to explore the differences between Arabic-English bilingual and
      monolingual Arabic children on a battery of executive functions. Prior research
      on the influence of bilingualism on cognitive abilities and executive functions
      has shown mixed results. Some results suggested that bilinguals perform
      significantly better than monolinguals, while others showed that monolinguals
      perform significantly better. Other studies showed no significant differences
      between both groups, findings which were argued to be due to methodological
      issues. A total of 50 Arabic monolingual and Arabic-English bilingual children
      ranging 7-10 years of age participated in the current study. Six executive
      function tasks, divided into two categories (inhibition of improper response
      tasks, and behavioral operational control tasks), were administered. Results did
      not show significant differences for most executive functions.

PMID- 25056577
TI  - Evolution of the hemagglutinin gene of H3N8 canine influenza virus in dogs.
AB  - With the widespread use of a recently developed canine influenza virus (CIV) H3N8
      vaccine, continual molecular evaluation of circulating CIVs is necessary for
      monitoring antigenic drift. The aim of this project was to further describe the
      genetic evolution of CIV, as well as determine any genetic variation within
      potential antigenic regions that might result in antigenic drift. To this end,
      the hemagglutinin gene of 19 CIV isolates from dogs residing in Colorado, New
      York, and South Carolina humane shelters was sequenced and compared to CIV
      strains isolated during 2003-2012. Phylogenetic analysis suggests that CIV might
      be diverging into two geographically distinct lineages. Using a mixed-effects
      model for evolution and single likelihood ancestor counting methods, several
      amino acid sites were found to be undergoing selection pressure. Additionally, a
      total of six amino acid changes were observed in two possible antigenic sites for
      CIVs isolated from Colorado and New York humane shelters between 2009 and 2011.
      As CIV isolates might be diverging into geographically distinct lineages, further
      experiments are warranted to determine the extent of antigenic drift occurring
      within circulating CIV.

PMID- 25056579
TI  - Expanding antiplatelet use for patients with stroke: the case for stroke of
      unknown type.

PMID- 25056581
TI  - Peripheral pulse measurement after ischemic stroke: A feasibility study.
AB  - OBJECTIVE: To investigate feasibility and diagnostic accuracy of measurement of
      the peripheral pulse (MPP) at the radial artery as a simple, noninvasive
      screening tool for paroxysmal atrial fibrillation (pAF) in patients after acute
      ischemic stroke. METHODS: Two hundred fifty-six patients with acute ischemic
      stroke and the patients' relatives at a tertiary stroke center were prospectively
      included. Participants were instructed for characteristics of atrial fibrillation
      (AF) in MPP using standardized educational material. Measurements of participants
      as well as a health care professional were then compared with simultaneous
      blinded ECG to evaluate diagnostic accuracy parameters. RESULTS: MPP by the
      health care professional or patients' relatives had a diagnostic sensitivity of
      96.5% and 76.5%, respectively, with 94.0% and 92.9% specificity for the detection
      of AF. Self-measurements were reliably performed by 89.1% of competent patients
      with a diagnostic sensitivity of 54.1% and 96.2% specificity. False-positive
      results were limited to 6 cases (2.7%) with a positive predictive value of 76.9%
      and a negative predictive value of 90.0%. CONCLUSION: With a low rate of false
      positive results, MPP offers an easy, ubiquitously available, noninvasive, first
      step screening tool to guide ECG diagnostics for pAF after ischemic stroke. The
      data warrant a prospective trial evaluating the efficacy of MPP-guided ECG
      diagnostics in secondary prevention after stroke, which is now underway.
      CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that MPP by
      patients or relatives accurately distinguishes AF from normal heart rhythm as
      compared with continuous ECG.

PMID- 25056580
TI  - Dementia with Lewy bodies: basis of cingulate island sign.
AB  - OBJECTIVES: To investigate clinical, imaging, and pathologic associations of the
      cingulate island sign (CIS) in dementia with Lewy bodies (DLB). METHODS: We
      retrospectively identified and compared patients with a clinical diagnosis of DLB
      (n=39); patients with Alzheimer disease (AD) matched by age, sex, and education
      (n=39); and cognitively normal controls (n=78) who underwent 18F
      fluorodeoxyglucose (FDG) and C11 Pittsburgh compound B (PiB)-PET scans. Among
      these patients, we studied those who came to autopsy and underwent Braak
      neurofibrillary tangle (NFT) staging (n=10). RESULTS: Patients with a clinical
      diagnosis of DLB had a higher ratio of posterior cingulate to precuneus plus
      cuneus metabolism, cingulate island sign (CIS), on FDG-PET than patients with AD
      (p<0.001), a finding independent of beta-amyloid load on PiB-PET (p=0.56).
      Patients with CIS positivity on visual assessment of FDG-PET fit into the group
      of high- or intermediate-probability DLB pathology and received clinical
      diagnosis of DLB, not AD. Higher CIS ratio correlated with lower Braak NFT stage
      (r=-0.96; p<0.001). CONCLUSIONS: Our study found that CIS on FDG-PET is not
      associated with fibrillar beta-amyloid deposition but indicates lower Braak NFT
      stage in patients with DLB. Identifying biomarkers that measure relative
      contributions of underlying pathologies to dementia is critical as
      neurotherapeutics move toward targeted treatments.

PMID- 25056582
TI  - Aspirin for acute stroke of unknown etiology in resource-limited settings: a
      decision analysis.
AB  - OBJECTIVE: To analyze the potential impact of aspirin on outcome at hospital
      discharge after acute stroke in resource-limited settings without access to
      neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH).
      METHODS: A decision analysis was conducted to evaluate aspirin use in all
      patients with acute stroke of unknown type for the duration of initial
      hospitalization. Data were obtained from the International Stroke Trial and
      Chinese Acute Stroke Trial. Predicted in-hospital mortality and stroke recurrence
      risk were determined across the worldwide reported range of the proportion of
      strokes caused by ICH. Sensitivity analyses were performed on aspirin-associated
      relative risks in patients with ICH. RESULTS: At the highest reported proportion
      of strokes due to ICH from a large epidemiologic study (34% in sub-Saharan
      Africa), aspirin initiation after acute stroke of undetermined etiology is
      predicted to reduce in-hospital mortality (from 85/1,000 without treatment to
      81/1,000 with treatment), in-hospital stroke recurrence (58/1,000 to 50/1,000),
      and combined risk of in-hospital mortality or stroke recurrence (127/1,000 to
      114/1,000). Benefits of aspirin therapy remained in sensitivity analyses across a
      range of plausible parameter estimates for relative risks associated with aspirin
      initiation after ICH. CONCLUSION: Aspirin treatment for the period of initial
      hospitalization after acute stroke of undetermined etiology is predicted to
      decrease acute stroke-related mortality and in-hospital stroke recurrence even at
      the highest reported proportion of acute strokes due to ICH. In the absence of
      clinical trials to test this approach empirically, clinical decisions require
      patient-specific evaluation of risks and benefits of aspirin in this context.

PMID- 25056583
TI  - Phenotypic overlap of alternating hemiplegia of childhood and CAPOS syndrome.

PMID- 25056584
TI  - House dust mite sublingual immunotherapy is safe and appears to be effective in
      moderate, persistent asthma.
AB  - BACKGROUND: The efficacy and safety of sublingual immunotherapy in house dust
      mite-induced asthma have yet to be firmly established. We report the results of a
      double-blind, placebo-controlled, randomized clinical trial performed in mainland
      China. METHODS: After a three-month baseline period, 484 asthmatic adults were
      randomized 2 : 1 to 12 months of daily treatment with either an aqueous,
      standardized, 300 index of reactivity mixture of Dermatophagoides pteronyssinus
      and Dermatophagoides farinae extracts or a placebo. The primary efficacy
      criterion was well-controlled asthma for at least 16 of the last 20 weeks of
      treatment. RESULTS: In the active (n = 308) and placebo (n = 157) groups, well
      controlled asthma was achieved by 85.4% and 81.5% of the patients, respectively
      (P = 0.244). A subsequent post hoc analysis by asthma severity revealed
      significant clinical benefits in actively treated subjects with moderate,
      persistent asthma at baseline [401-800 MUg budesonide/day (n = 175)], with
      greater achievement of well-controlled asthma (80.5% and 66.1% for the active
      treatment and placebo groups, respectively; P = 0.021) and totally controlled
      asthma (54.0% and 33.9%, respectively, P = 0.008), a higher percentage of
      patients with an asthma control questionnaire score < 0.75 (56.6% and 40.0%,
      respectively; P = 0.039) and a greater mean reduction in inhaled corticosteroid
      use (218.5 MUg and 126.2 MUg, respectively; P = 0.004). The active vs placebo
      differences in disease control and corticosteroid use were not significant for
      mild, persistent asthma. No treatment-related serious adverse events were
      reported. CONCLUSIONS: Sublingual mite allergen immunotherapy was well tolerated
      in adult asthmatics and effectively controlled disease in patients with moderate
      (but not mild) persistent asthma (ClinicalTrials.gov: NCT00660452).

PMID- 25056585
TI  - Are oxidized low-density lipoprotein and C-reactive protein markers of
      atherosclerosis in nephrotic children?
AB  - BACKGROUND: Lipid disorders are known to be linked to disturbance in oxidative
      reactions and play an important role in the progression and complications of
      idiopathic nephrotic syndrome (INS). AIMS: The aim of this study was to assess
      oxidized low-density lipoprotein (oxLDL), high-sensitive C-reactive protein (hs
      CRP) serum concentrations and other parameters of lipid metabolism in children
      with INS during relapse and remission of proteinuria. METHODS: The examination
      was performed on 23 children and adolescents diagnosed with INS. Reference group
      consisted of 22 participants. The study was carried out twice: in the relapse of
      INS (A) and in remission of proteinuria during glucocorticoid treatment (B).
      RESULTS: OxLDL was higher in INS patients, in both examinations when compared
      with reference participants. hs-CRP showed no differences between nephrotic and
      healthy children. We found higher concentration of oxLDL in children, who where
      frequent relapsers. Cholesterol, triglycerides/high density lipoprotein
      cholesterol and platelets were higher in INS patients (both A and B) in
      comparison with healthy children. CONCLUSIONS: We observed presence of pro
      atherogenic lipid profile in INS. Elevation of oxLDL may reflect increased
      oxidative stress and higher risk of atherosclerosis in INS, therefore it seems to
      be relevant to find patients of risk of atherosclerosis to consider lipid
      lowering treatment with antioxidants.

PMID- 25056586
TI  - Pancreatic metastasectomy: experience of the Irish National Surgical Centre for
      Pancreatic Cancer.
AB  - BACKGROUND: Metastatic tumours of the pancreas are rare and the optimal
      management of these tumours remains unclear, given the paucity of data existing
      in the literature. We report our experience of pancreatic metastasectomy.
      METHODS: Data were reviewed on all patients who underwent pancreatic resection
      for pathologically confirmed metastatic lesions over a consecutive 7-year period.
      RESULTS: Seven patients (two men and five women) underwent a pancreatectomy for a
      metastatic pancreatic tumour. The primary tumours were renal cell carcinoma (n =
      3), colorectal carcinoma (n = 2) and leiomyosarcoma (n = 2). There was no
      operative mortality. Postoperative morbidities occurred in two patients. The
      median follow-up was 49 months (range 17-76). Overall 1- and 2-year survivals
      were 100 and 86 %, respectively, with a 2-year disease-free survival of 72 %.
      CONCLUSIONS: Our series further supports that pancreatic metastasectomy can be
      performed safely and achieves acceptable survival outcomes.

PMID- 25056587
TI  - Factors associated with components of arterial pressure among older individuals
      (the multinational MEDIS study): the role of the Mediterranean diet and alcohol
      consumption.
AB  - The aim of this work was to evaluate factors associated with arterial blood
      pressure in a sample of older Mediterranean people without known cardiovascular
      disease. During 2005 to 2011, 2813 older (aged 65-100 years) individuals from 22
      Mediterranean islands and the rural Mani region (Peloponnesus) voluntarily
      enrolled. Standard procedures were used to determine arterial BP and pulse
      pressure and for the evaluation of dietary habits (including tea and alcoholic
      beverages consumption), lifestyle, and anthropometric and clinical
      characteristics of the participants. Participants who reported low alcohol
      consumption (ie, 0-1 glasses per day) were less likely to have hypertension (odds
      ratio, 0.34; 95% confidence interval, 0.14-0.84) as compared with those who
      reported high alcohol consumption (ie, 5+ glasses per day). Adherence to the
      Mediterranean diet was inversely associated with mean arterial pressure (beta
      coefficient, -0.18; 95% confidence interval, -0.33 to -0.16). Alcohol drinking
      remains an important modifiable risk factor for hypertension. Adherence to the
      Mediterranean diet was associated with decreased arterial peripheral resistance.

PMID- 25056588
TI  - Factors influencing surface CO2 variations in LPRU, Thailand and IESM,
      Philippines.
AB  - Surface carbon dioxide concentrations were measured using a non-dispersive
      infrared carbon dioxide sensor at Lampang Rajabhat University from April to May
      2013 and at the University of the Philippines-Diliman campus starting September
      2013. Factors influencing the variations in these measurements were determined
      using multiple linear regression and a Lagrangian transport model. Air
      temperature and sea level pressure were the dominant meteorological factors that
      affect the CO2 variations. However, these factors are not enough. Surface CO2
      flux and transboundary transport needs to be considered as well. 

PMID- 25056589
TI  - Nephrotic syndrome presenting as primary peritonitis in a male adolescent.

PMID- 25056592
TI  - The role of the MRTF-A/SRF pathway in ocular fibrosis.
AB  - Tissue contraction and fibrosis are major causes of morbidity in the human body.
      In the eye in particular, fibrosis and scarring are responsible for the
      pathogenesis or failure of treatment of all major blinding diseases, with
      postoperative wound healing responses posing a major problem for most ocular
      surgery on a worldwide scale. This is one of the largest areas of unmet need in
      ophthalmology, with currently no antifibrotic treatments available clinically.
      This review focuses on the ubiquitous myocardin-related transcription
      factor/serum response factor (MRTF-A/SRF) transcription pathway as a potential
      novel therapeutic target in fibrotic eye diseases. It describes how the MRTF
      A/SRF pathway is intricately linked to all the key regulators and pathways in
      ocular fibrosis, and how it could potentially lead to a new avenue of
      antifibrotic therapies in the future. 

PMID- 25056593
TI  - Cardiac troponin I and T as prognostic markers in cats with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Myocardial injury detected by cardiac troponin I and T (cTnI and
      cTnT) in cardiac disease is associated with increased risk of death in humans and
      dogs. HYPOTHESIS: Presence of myocardial injury predicts long-term death in cats
      with hypertrophic cardiomyopathy (HCM), and ongoing myocardial injury reflects
      change in left ventricular wall thickness over time. ANIMALS: Thirty-six cats
      with primary HCM. METHODS: Prospective cohort study. Cats with HCM were included
      consecutively and examined every 6 months. Echocardiography, ECG, blood pressure,
      and serum cTnI and cTnT were evaluated at each visit. Cox proportional hazards
      regression analysis was performed to evaluate prognostic potential of serum
      troponin concentrations at admission and subsequent examinations. Correlations
      were used to examine associations between troponin concentrations and cardiac
      hypertrophy. RESULTS: Troponin concentrations at admission were median [range]
      0.14 [0.004-1.02] ng/mL for cTnI, and 13 [13-79.5] ng/L for cTnT. Both were
      prognostic for death (P = .032 and .026) as were the last available
      concentrations of each (P = .016 and .003). The final cTnT concentration was a
      significant predictor of death even when adjusting for the admission
      concentration (P = .043). In a model containing both markers, only cTnT remained
      significant (P = .043). Left ventricular free wall thickness at end-diastole
      (LVFWd) at admission was correlated with cTnI at admission (r = 0.35, P = .035),
      however no significant correlations (r = 0.2-0.31, P = .074-.26) were found
      between changes in troponin concentrations and left ventricular thickness over
      time. CONCLUSIONS AND CLINICAL IMPORTANCE: Myocardial injury is part of the
      pathophysiology leading to disease progression and death. Low sensitivities and
      specificities prevent outcome prediction in individual cats.

PMID- 25056594
TI  - Chronic uranium exposure dose-dependently induces glutathione in rats without any
      nephrotoxicity.
AB  - Uranium is a heavy metal naturally found in the earth's crust that can
      contaminate the general public population when ingested. The acute effect and
      notably the uranium nephrotoxicity are well known but knowledge about the effect
      of chronic uranium exposure is less clear. In a dose-response study we sought to
      determine if a chronic exposure to uranium is toxic to the kidneys and the liver,
      and what the anti-oxidative system plays in these effects. Rats were contaminated
      for 3 or 9 months by uranium in drinking water at different concentrations (0, 1,
      40, 120, 400, or 600 mg/L). Uranium tissue content in the liver, kidneys, and
      bones was linear and proportional to uranium intake after 3 and 9 months of
      contamination; it reached 6 MUg per gram of kidney tissues for the highest
      uranium level in drinking water. Nevertheless, no histological lesions of the
      kidney were observed, nor any modification of kidney biomarkers such as
      creatinine or KIM-1. After 9 months of contamination at and above the 120-mg/L
      concentration of uranium, lipid peroxidation levels decreased in plasma, liver,
      and kidneys. Glutathione concentration increased in the liver for the 600-mg/L
      group, in the kidney it increased dose dependently, up to 10-fold, after 9 months
      of contamination. Conversely, chronic uranium exposure irregularly modified gene
      expression of antioxidant enzymes and activities in the liver and kidneys. In
      conclusion, chronic uranium exposure did not induce nephrotoxic effects under our
      experimental conditions, but instead reinforced the antioxidant system,
      especially by increasing glutathione levels in the kidneys.

PMID- 25056595
TI  - Striatal morphology is associated with tobacco cigarette craving.
AB  - The striatum has a clear role in addictive disorders and is involved in drug
      related craving. Recently, enhanced striatal volume was associated with greater
      lifetime nicotine exposure, suggesting a bridge between striatal function and
      structural phenotypes. To assess this link between striatal structure and
      function, we evaluated the relationship between striatal morphology and this
      brain region's well-established role in craving. In tobacco smokers, we assessed
      striatal volume, surface area, and shape using a new segmentation methodology
      coupled with local shape indices. Striatal morphology was then related with two
      measures of craving: state-based craving, assessed by the brief questionnaire of
      smoking urges (QSU), and craving induced by smoking-related images. A positive
      association was found between left striatal volume and surface area with both
      measures of craving. A more specific relationship was found between both craving
      measures and the dorsal, but not in ventral striatum. Evaluating dorsal striatal
      subregions showed a single relationship between the caudate and QSU. Although cue
      induced craving and the QSU were both associated with enlarged striatal volume
      and surface area, these measures were differentially associated with global or
      more local striatal volumes. We also report a connection between greater right
      striatal shape deformations and cue-induced craving. Shape deformations
      associated with cue-induced craving were specific to striatal subregions involved
      in habitual responding to rewarding stimuli, which is relevant given the habitual
      nature of cue-induced craving. The current findings confirm a relationship
      between striatal function and morphology and suggest that variation in striatal
      morphology may be a biomarker for craving severity. 

PMID- 25056596
TI  - Activation energies control the macroscopic properties of physically cross-linked
      materials.
AB  - Here we show the preparation of a series of water-based physically cross-linked
      polymeric materials utilizing cucurbit[8]uril (CB[8]) ternary complexes
      displaying a range of binding, and therefore cross-linking, dynamics. We
      determined that the mechanical strength of these materials is correlated directly
      with a high energetic barrier for the dissociation of the CB[8] ternary complex
      cross-links, whereas facile and rapid self-healing requires a low energetic
      barrier to ternary complex association. The versatile CB[8] ternary complex has,
      therefore, proven to be a powerful asset for improving our understanding of
      challenging property-structure relationships in supramolecular systems and their
      associated influence on the bulk behavior of dynamically cross-linked materials. 

PMID- 25056597
TI  - Serum tryptase, mast cells positive to tryptase and microvascular density
      evaluation in early breast cancer patients: possible translational significance.
AB  - BACKGROUND: Tryptase is a serine protease released from mast cells that plays a
      role in tumor angiogenesis. In this study we aimed to evaluate serum tryptase
      levels in 105 female early breast cancer patients before (STLBS) and after
      (STLAS) radical surgical resection, mast cell density positive to tryptase
      (MCDPT) and microvascular density (MVD). METHODS: STLBS and STLAS were assessed
      using the UniCAP Tryptase Fluoroenzyme immunoassay. Tumor sections were
      immunostained with a primary anti-tryptase antibody and an anti-CD-34 antibody by
      means of immunohistochemistry. RESULTS: The mean +/- 1 standard deviation STLBS
      and STLAS was 7.18 +/- 2.63 MUg/L, and 5.13 +/- 2.21 respectively and a
      significant difference between mean levels was found (p = 0.0001) by student t
      test. A strong correlation between STLBS and MVD (r = 0.81, p = 0.0001); STLBS
      and MCDPT (r = 0.69, p = 0.003); and MCDPT and MVD (r = 0.77; p = 0.0001) was
      found. CONCLUSIONS: Results demonstrated higher STLBS in breast cancer patients,
      indicating an involvement of MC tryptase in breast cancer angiogenesis.
      Therefore, serum tryptase levels may play a role as a novel surrogate angiogenic
      marker predictive of response to radical surgery in breast cancer patients. In
      this patients setting, it's intriguing to hypothesize that tryptase inhibitors
      might be evaluated in clinical trials.

PMID- 25056598
TI  - Targeting human C-type lectin-like molecule-1 (CLL1) with a bispecific antibody
      for immunotherapy of acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML), which is the most common acute adult leukemia and
      the second most common pediatric leukemia, still has a poor prognosis. Human C
      type lectin-like molecule-1 (CLL1) is a recently identified myeloid lineage
      restricted cell surface marker, which is overexpressed in over 90% of AML patient
      myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a
      novel bispecific antibody, alphaCLL1-alphaCD3, using the genetically encoded
      unnatural amino acid, p-acetylphenylalanine. The resulting alphaCLL1-alphaCD3
      recruits cytotoxic T cells to CLL1 positive cells, and demonstrates potent and
      selective cytotoxicity against several human AML cell lines and primary AML
      patient derived cells in vitro. Moreover, alphaCLL1-alphaCD3 treatment completely
      eliminates established tumors in an U937 AML cell line xenograft model. These
      results validate the clinical potential of CLL1 as an AML-specific antigen for
      the generation of a novel immunotherapeutic for AML.

PMID- 25056599
TI  - Associations between early life stress and gene methylation in children.
AB  - Children exposed to extreme stress are at heightened risk for developing mental
      and physical disorders. However, little is known about mechanisms underlying
      these associations in humans. An emerging insight is that children's social
      environments change gene expression, which contributes to biological
      vulnerabilities for behavioral problems. Epigenetic changes in the glucocorticoid
      receptor gene, a critical component of stress regulation, were examined in whole
      blood from 56 children aged 11-14 years. Children exposed to physical
      maltreatment had greater methylation within exon 1F in the NR3C1 promoter region
      of the gene compared to nonmaltreated children, including the putative NGFI-A
      (nerve growth factor) binding site. These results highlight molecular mechanisms
      linking childhood stress with biological changes that may lead to mental and
      physical disorders.

PMID- 25056600
TI  - Crossover between weak antilocalization and weak localization of bulk states in
      ultrathin Bi2Se3 films.
AB  - We report transport studies on the 5 nm thick Bi2Se3 topological insulator films
      which are grown via molecular beam epitaxy technique. The angle-resolved
      photoemission spectroscopy data show that the Fermi level of the system lies in
      the bulk conduction band above the Dirac point, suggesting important contribution
      of bulk states to the transport results. In particular, the crossover from weak
      antilocalization to weak localization in the bulk states is observed in the
      parallel magnetic field measurements up to 50 Tesla. The measured magneto
      resistance exhibits interesting anisotropy with respect to the orientation of
      parallel magnetic field B// and the current I, signifying intrinsic spin-orbit
      coupling in the Bi2Se3 films. Our work directly shows the crossover of quantum
      interference effect in the bulk states from weak antilocalization to weak
      localization. It presents an important step toward a better understanding of the
      existing three-dimensional topological insulators and the potential applications
      of nano-scale topological insulator devices.

PMID- 25056601
TI  - High-riding innominate artery encountered during neck surgery.

PMID- 25056602
TI  - Effect of total dose and fraction size on survival of patients with locally
      recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy:
      a phase 2, single-center, randomized controlled trial.
AB  - BACKGROUND: The optimal model of total dose and fraction size for patients with
      locally recurrent nasopharyngeal carcinoma treated with intensity-modulated
      radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2
      clinical trial to investigate the efficacy of 2 different models, with the
      objective of determining an optimal model. METHODS: Between January 2003 and
      December 2007, a total of 117 patients with locally recurrent nonmetastatic
      nasopharyngeal carcinoma were randomized to 2 different models of total dose and
      fraction size: group A (59 patients) received 60 gray in 27 fractions and group B
      (58 patients) received 68 gray in 34 fractions. Both groups received 5 daily
      fractions per week. All patients received IMRT alone. RESULTS: The median follow
      up was 25.0 months. The 5-year overall survival in group A was higher than that
      in group B (44.2% vs 30.3%; P =.06), and the local failure-free survival in group
      A was slightly lower than that in group B (63.7% vs 71.0%; P =.41). Severe late
      complications were the main cause of death. The incidences of mucosal necrosis
      and massive hemorrhage in patients in group B were significantly higher than
      those among patients in group A at 50.8% versus 28.8% (P =.02) and 31.0% versus
      18.6% (P =.12), respectively. Tumor volume (P<.01) and model of total dose and
      fraction size (P =.03) were found to be significant factors for mucosal necrosis
      and massive hemorrhage. CONCLUSIONS: Appropriately decreasing the total dose and
      increasing the fraction size can achieve local control similar to that achieved
      with a higher dose after IMRT; furthermore, it can improve overall survival by
      significantly reducing the incidence of severe late complications including
      mucosal necrosis and massive hemorrhage.

PMID- 25056603
TI  - Third-order nonlinear optical properties of one-dimensional open-shell molecular
      aggregates composed of phenalenyl radicals.
AB  - The impact of intermolecular interactions on the third-order nonlinear optical
      (NLO) properties of open-shell molecular aggregates has been elucidated by
      considering one-dimensional aggregates of pi-pi stacked phenalenyl radicals with
      different intermolecular distances and the long-range corrected spin-unrestricted
      density functional theory method. In the phenalenyl dimer, which can be
      considered as a diradicaloid system, the diradical character strongly depends on
      the intermolecular distance, and the larger the intermolecular distance is, the
      larger the diradical character becomes. Then, around the equilibrium stacking
      distance that corresponds to an intermediate diradical character, its second
      hyperpolarizability (gamma) is maximized and its value per monomer exhibits about
      a 30-fold enhancement with respect to the isolated phenalenyl monomer. This
      suggests that equilibrium is an optimal compromise between localization and
      delocalization of the radical electron pairs in such pancake bonding. No such
      effect was observed for the closed-shell coronene dimer. Moreover, when going
      from the dimer (diradical) to the tetramer (tetraradical), the gamma-enhancement
      ratio increases nonlinearly with the aggregate size, whereas switching from the
      singlet to the highest spin (quintet) state causes a significant reduction of
      gamma. Finally, for the tetramer, another one-order enhancement of gamma is
      achieved for the dicationic singlet relative to its singlet neutral state. These
      results demonstrate the key role of intermolecular pi-pi stacking interactions
      and charge in open-shell (supra)molecular systems to achieve enhanced third-order
      NLO properties. 

PMID- 25056604
TI  - The effect of ezetimibe on androgen production in hypercholesterolemic women with
      polycystic ovary syndrome.
AB  - AIMS: Statin therapy was found to reduce circulating androgen levels in patients
      with polycystic ovary syndrome (PCOS). No similar data are available for
      ezetimibe. METHODS: The study included 14 women with PCOS and
      hypercholesterolemia, intolerant to statins or having contraindications to this
      treatment, who were treated with ezetimibe (10 mg daily). They were compared with
      14 matched women with both of these disorders receiving simvastatin (40 mg
      daily). Plasma lipids, glucose homeostasis markers, and serum levels of
      androgens, sex hormone-binding globulin, and gonadotropins were assessed at
      baseline and after 3 months of treatment. RESULTS: Both simvastatin and ezetimibe
      decreased plasma levels of total and LDL cholesterol. Ezetimibe, but not
      simvastatin, slightly reduced insulin resistance. Simvastatin decreased serum
      levels of total testosterone (-23%, P < 0.001), free testosterone (-32%, P <
      0.001), androstendione (-20%, P < 0.01), and dehydroepiandrosterone sulfate (
      17%, P < 0.05), as well as tended to reduce the luteinizing hormone/follicle
      stimulating hormone ratio (-23%, P = 0.095). Ezetimibe only insignificantly
      reduced serum levels of free testosterone (-14%, P = 0.098). There were no
      differences in the effects of simvastatin on circulating hormone levels between
      insulin-resistant and insulin-sensitive subjects. In turn, the effect of
      ezetimibe on free testosterone levels was stronger in insulin-resistant patients.
      CONCLUSIONS: Although ezetimibe and simvastatin are equipotent in lowering lipid
      levels in hypercholesterolemic patients with coexisting PCOS, simvastatin
      exhibits a more pronounced effect on circulating androgen levels in this group of
      patients.

PMID- 25056605
TI  - Stanniocalcin-1 promotes metastasis in a human breast cancer cell line through
      activation of PI3K.
AB  - Stanniocalcin-l (STC-1) is a secreted glycoprotein hormone that regulates calcium
      and phosphate homeostasis. STC-1 expression is upregulated in several cancers
      including breast cancer, and has been shown to be prognostic. Although these
      clinical observations implicate STC-1 as a potential tumor marker, it is still
      unclear whether STC-1 confers a malignant phenotype. In this study, this question
      was addressed by overexpressing STC-1 in the human breast cancer cell line MDA-MB
      231 and examining the resultant phenotype in vitro and in vivo. Overexpression of
      STC-1 enhanced invasiveness of MDA-MB-231 cells in vitro and promoted their lung
      metastasis in vivo, while having no effect on proliferation, adhesion, or
      proteinase activity. The addition of soluble STC-1 to MDA-MB-231 cultures
      resulted in the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling
      pathway, suggesting a mechanistic basis for the observed increases in cell
      motility and metastasis. Taken together, it was indicated that secreted STC-1
      promotes metastatic potential of breast cancer cells via activation of PI3K/AKT. 

PMID- 25056606
TI  - Reversible hydrogel-solution system of silk with high beta-sheet content.
AB  - Silkworm silk has been widely used as a textile fiber, as biomaterials and in
      optically functional materials due to its extraordinary properties. The beta
      sheet-rich natural nanofiber units of about 10-50 nm in diameter are often
      considered the origin of these properties, yet it remains unclear how silk self
      assembles into these hierarchical structures. A new system composed of beta-sheet
      rich silk nanofibers about 10-20 nm in diameter is reported here, where these
      nanofibers formed into "flowing hydrogels" at 0.5-2% solutions and could be
      transformed back into the solution state at lower concentrations, even with a
      high beta-sheet content. This is in contrast with other silk processed materials,
      where significant beta-sheet content negates reversibility between solution and
      solid states. These fibers are formed by regulating the self-assembly process of
      silk in aqueous solution, which changes the distribution of negative charges
      while still supporting beta-sheet formation in the structures. Mechanistically,
      there appears to be a shift toward negative charges along the outside of the silk
      nanofibers in our present study, resulting in a higher zeta potential (above -50
      mV) than previous silk materials which tend to be below -30 mV. The higher
      negative charge on silk nanofibers resulted in electrostatic repulsion strong
      enough to negate further assembly of the nanofibers. Changing silk concentration
      changed the balance between hydrophobic interactions and electrostatic repulsion
      of beta-sheet-rich silk nanofibers, resulting in reversible hydrogel-solution
      transitions. Furthermore, the silk nanofibers could be disassembled into shorter
      fibers and even nanoparticles upon ultrasonic treatment following the transition
      from hydrogel to solution due to the increased dispersion of hydrophobic smaller
      particles, without the loss of beta-sheet content, and with retention of the
      ability to transition between hydrogel and solution states through reversion to
      longer nanofibers during self-assembly. These reversible solution-hydrogel
      transitions were tunable with ultrasonic intensity, time, or temperature. 

PMID- 25056607
TI  - Long-term efficiency of mesenchymal stromal cell-mediated CD-MSC/5FC therapy in
      human melanoma xenograft model.
AB  - Mesenchymal stromal cells (MSC) can be exploited as cellular delivery vehicles
      for the enzymes converting non-toxic prodrugs to toxic substances. Because of
      their inherent chemoresistance, they exert potent bystander and antitumor effect.
      Here we show that the human adipose tissue-derived MSC expressing fusion yeast
      cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) in combination with
      5-fluorocytosine (5FC) mediated a long-term tumor-free survival in the 83.3% of
      tumor-bearing animals. CD-MSC/5FC treatment induced cytotoxicity against model
      human melanoma cells EGFP-A375. Only 4% of the therapeutic CD-MSC cells
      eliminated >98.5% of the tumor cells in vitro. Long-term tumor-free survival was
      confirmed in 15 out of the 18 animals. However, repeatedly used CD-MSC/5FC
      therapeutic regimen generated more aggressive and metastatic variant of the
      melanoma cells EGFP-A375/Rel3. These cells derived from the refractory
      xenotransplants exhibited increased resistance to the CD-MSC/5FC treatment,
      altered cell adhesion, migration, tumorigenic and metastatic properties. However,
      long-term curative effect was achieved by the augmentation of the CD-MSC/5FC
      regimen along with the inhibition of c-Met/hepatocyte growth factor signaling
      axis in this aggressive melanoma derivative. In summary, the CD-MSC/5FC regimen
      can be regarded as a very effective antitumor approach to achieve long-term tumor
      free survival as demonstrated on a mouse model of aggressive human melanoma
      xenografts. 

PMID- 25056608
TI  - Differential targeting of feline photoreceptors by recombinant adeno-associated
      viral vectors: implications for preclinical gene therapy trials.
AB  - The cat is emerging as a promising large animal model for preclinical testing of
      retinal dystrophy therapies, for example, by gene therapy. However, there is a
      paucity of studies investigating viral vector gene transfer to the feline retina.
      We therefore sought to study the tropism of recombinant adeno-associated viral
      (rAAV) vectors for the feline outer retina. We delivered four rAAV serotypes:
      rAAV2/2, rAAV2/5, rAAV2/8 and rAAV2/9, each expressing green fluorescent protein
      (GFP) under the control of a cytomegalovirus promoter, to the subretinal space in
      cats and, for comparison, mice. Cats were monitored for gene expression by in
      vivo imaging and cellular tropism was determined using immunohistochemistry. In
      cats, rAAV2/2, rAAV2/8 and rAAV2/9 vectors induced faster and stronger GFP
      expression than rAAV2/5 and all vectors transduced the retinal pigment epithelium
      (RPE) and photoreceptors. Unlike in mice, cone photoreceptors in the cat retina
      were more efficiently transduced than rod photoreceptors. In mice, rAAV2/2 only
      transduced the RPE whereas the other vectors also transduced rods and cones.
      These results highlight species differences in cellular tropism of rAAV vectors
      in the outer retina. We conclude that rAAV serotypes are suitable for use for
      retinal gene therapy in feline models, particularly when cone photoreceptors are
      the target cell. 

PMID- 25056611
TI  - Targeted testing in primary care demonstrates high prevalence of hepatitis B
      infection within the Slovak-Roma population in Sheffield, UK.

PMID- 25056610
TI  - The mental health of asbestos-exposed subjects with pleural abnormalities.
AB  - PURPOSE: To examine the effect of knowledge of radiographic abnormalities on the
      mental health of asbestos-exposed people with and without pleural abnormalities.
      METHODS: Subjects were former asbestos mine and mill workers and residents of the
      mining town who had participated in an annual health review program. Pleural
      abnormalities (pleural plaques, diffuse pleural thickening and asbestosis) were
      determined from plain chest X-rays. All Participants completed a questionnaire on
      mental health status (SF-12) and locus of control (LOC). RESULTS: There were no
      significant differences between asbestos-exposed people with and without
      radiographic abnormalities for either the SF-12 mental health score or LOC.
      However, the asbestos-exposed cohorts had lower mental health scores compared
      with a random sample of the local population. CONCLUSION: The presence of pleural
      abnormalities did not further affect the mental health of asbestos-exposed people
      beyond a decrement associated with exposure per se.

PMID- 25056609
TI  - A dual-reporter, diagnostic vector for prostate cancer detection and tumor
      imaging.
AB  - Detection of prostate-specific antigen (PSA) as a screening strategy for prostate
      cancer is limited by the inability of the PSA test to differentiate between
      malignant cancer and benign hyperplasia. Here, we report the use of a cancer
      specific promoter, inhibition of differentiation-1 (Id1), to drive a dual
      reporter system (Ad5/3-Id1-SEAP-Id1-mCherry) designed for detection of prostate
      cancer using a blood-based reporter-secreted embryonic alkaline phosphatase
      (SEAP) and tumor visualization using a fluorescent reporter protein, mCherry. In
      human prostate tumors, Id1 levels are correlated with increased Gleason grade and
      disease progression. To evaluate the performance of the dual-reporter system, a
      prostate cell panel with varying aggressive phenotypes was tested. Following
      infection with the Ad5/3-Id1-SEAP-Id1-mCherry vector, expression of the SEAP and
      mCherry reporters was shown to increase with increasing levels of cellular Id1.
      No correlation was observed between Id1 and PSA. To evaluate in vivo performance,
      flank tumors were grown in athymic male mice using three prostate cancer cell
      lines. Following intra-tumoral injection of the vector, tumors formed by cells
      with high Id1 had the greatest reporter expression. Interestingly, tumors with
      the lowest levels of Id1 and reporter expression produced the greatest amounts of
      PSA. These data support the use of Ad5/3-Id1-SEAP-Id1-mCherry as a predictor of
      prostate cancer malignancy and as a strategy for tumor localization. 

PMID- 25056612
TI  - Journal of Huntington's Disease.

PMID- 25056613
TI  - Huntington's Disease - A Brief Historical Perspective.
AB  - Although the disease today known as Huntington's was described as early as the
      mid-19th century, knowledgeable physicians despaired of finding successful
      therapies and affected families largely kept it hidden. Starting in the late 1960
      s, the confluence of grass-roots advocacy by HD family members, advances in
      Parkinson's treatment, and the development of molecular genetics and neuroscience
      helped turn HD into a focus of growing biomedical research. While therapies lag
      behind laboratory discoveries, disease altering interventions are now moving
      closer to the clinic. The Journal of Huntington's Disease is a welcome new
      resource in this effort. 

PMID- 25056615
TI  - Adaptive evolution in urban ecosystems.
AB  - Urban ecologists have demonstrated that cities are functioning ecosystems. It
      follows then that species living in these contexts should participate in and
      experience the same suite of biological processes, including evolution, that have
      occupied scientists for centuries in more "natural" contexts. In fact, urban
      ecosystems with myriad novel contexts, pressures, and species rosters provide
      unprecedentedly potent evolutionary stimuli. Here, we present the case for
      studying adaptive evolution in urban settings. We then review and synthesize
      techniques into a coherent approach for studying adaptive evolution in urban
      settings that combines observations of phenotypic divergence, measurements of
      fitness benefits of novel genetically based phenotypes, and experimental
      manipulations of potential drivers of adaptation. We believe that studying
      evolution in urban contexts can provide insights into fundamental evolutionary
      biology questions on rate, direction, and repeatability of evolution, and may
      inform species and ecosystem service conservation efforts. 

PMID- 25056616
TI  - Amygdaloid and non-amygdaloid fear both influence avoidance of risky foraging in
      hungry rats.
AB  - Considerable evidence seems to show that emotional and reflex reactions to feared
      situations are mediated by the amygdala. It might therefore seem plausible to
      expect that amygdala-coded fear should also influence decisions when animals make
      choices about instrumental actions. However, there is not good evidence of this.
      In particular, it appears, though the literature is conflicted, that once
      learning is complete, the amygdala may often not be involved in instrumental
      avoidance behaviours. It is therefore of interest that we have found in rats
      living for extended periods in a semi-naturalistic 'closed economy', where they
      were given random shocks in regions that had to be entered to obtain food,
      choices about feeding behaviour were in fact influenced by amygdala-coded fear,
      in spite of the null effect of amygdalar lesions on fear of dangerous location
      per se. We suggest that avoidance of highly motivated voluntary behaviour does
      depend in part on fear signals originating in the amygdala. Such signalling may
      be one role of well-known projections from amygdala to cortico-striate circuitry.

PMID- 25056617
TI  - Demography can favour female-advantageous alleles.
AB  - When female fecundity is relatively independent of male abundance, while male
      reproduction is proportional to female abundance, females have a larger effect on
      population dynamics than males (i.e. female demographic dominance). This
      population dynamic phenomenon might not appear to influence evolution, because
      male and female genomes still contribute equally much to the next generation.
      However, here we examine two evolutionary scenarios to provide a proof of
      principle that spatial structure can make female demographic dominance matter.
      Our two simulation models combine dispersal evolution with local adaptation
      subjected to intralocus sexual conflict and environmentally driven sex ratio
      biases, respectively. Both models have equilibria where one environment (without
      being intrinsically poorer) has so few reproductive females that trait evolution
      becomes disproportionately determined by those environments where females survive
      better (intralocus sexual conflict model), or where daughters are overproduced
      (environmental sex determination model). Surprisingly, however, the two facts
      that selection favours alleles that benefit females, and population growth is
      improved when female fitness is high, together do not imply that all measures of
      population performance are improved. The sex-specificity of the source-sink
      dynamics predicts that populations can evolve to fail to persist in habitats
      where alleles do poorly when expressed in females. 

PMID- 25056618
TI  - The dynamics of sperm cooperation in a competitive environment.
AB  - Sperm cooperation has evolved in a variety of taxa and is often considered a
      response to sperm competition, yet the benefit of this form of collective
      movement remains unclear. Here, we use fine-scale imaging and a minimal
      mathematical model to study sperm aggregation in the rodent genus Peromyscus. We
      demonstrate that as the number of sperm cells in an aggregate increase, the group
      moves with more persistent linearity but without increasing speed. This benefit,
      however, is offset in larger aggregates as the geometry of the group forces sperm
      to swim against one another. The result is a non-monotonic relationship between
      aggregate size and average velocity with both a theoretically predicted and
      empirically observed optimum of six to seven sperm per aggregate. To understand
      the role of sexual selection in driving these sperm group dynamics, we compared
      two sister-species with divergent mating systems. We find that sperm of
      Peromyscus maniculatus (highly promiscuous), which have evolved under intense
      competition, form optimal-sized aggregates more often than sperm of Peromyscus
      polionotus (strictly monogamous), which lack competition. Our combined
      mathematical and experimental study of coordinated sperm movement reveals the
      importance of geometry, motion and group size on sperm velocity and suggests how
      these physical variables interact with evolutionary selective pressures to
      regulate cooperation in competitive environments. 

PMID- 25056619
TI  - Population size, habitat fragmentation, and the nature of adaptive variation in a
      stream fish.
AB  - Whether and how habitat fragmentation and population size jointly affect adaptive
      genetic variation and adaptive population differentiation are largely unexplored.
      Owing to pronounced genetic drift, small, fragmented populations are thought to
      exhibit reduced adaptive genetic variation relative to large populations. Yet
      fragmentation is known to increase variability within and among habitats as
      population size decreases. Such variability might instead favour the maintenance
      of adaptive polymorphisms and/or generate more variability in adaptive
      differentiation at smaller population size. We investigated these alternative
      hypotheses by analysing coding-gene, single-nucleotide polymorphisms associated
      with different biological functions in fragmented brook trout populations of
      variable sizes. Putative adaptive differentiation was greater between small and
      large populations or among small populations than among large populations. These
      trends were stronger for genetic population size measures than demographic ones
      and were present despite pronounced drift in small populations. Our results
      suggest that fragmentation affects natural selection and that the changes
      elicited in the adaptive genetic composition and differentiation of fragmented
      populations vary with population size. By generating more variable evolutionary
      responses, the alteration of selective pressures during habitat fragmentation may
      affect future population persistence independently of, and perhaps long before,
      the effects of demographic and genetic stochasticity are manifest.

PMID- 25056620
TI  - Is adaptation to climate change really constrained in niche specialists?
AB  - Species with restricted distributions make up the vast majority of biodiversity.
      Recent evidence suggests that Drosophila species with restricted tropical
      distributions lack genetic variation in the key trait of desiccation resistance.
      It has therefore been predicted that tropically restricted species will be
      limited in their evolutionary response to future climatic changes and will face
      higher risks of extinction. However, these assessments have been made using
      extreme levels of desiccation stress (less than 10% relative humidity (RH)) that
      extend well beyond the changes projected for the wet tropics under climate change
      scenarios over the next 30 years. Here, we show that significant evolutionary
      responses to less extreme (35% RH) but more ecologically realistic levels of
      climatic change and desiccation stress are in fact possible in two species of
      rainforest restricted Drosophila. Evolution may indeed be an important means by
      which sensitive rainforest-restricted species are able to mitigate the effects of
      climate change. 

PMID- 25056621
TI  - Mortality trajectory analysis reveals the drivers of sex-specific epidemiology in
      natural wildlife-disease interactions.
AB  - In animal populations, males are commonly more susceptible to disease-induced
      mortality than females. However, three competing mechanisms can cause this sex
      bias: weak males may simultaneously be more prone to exposure to infection and
      mortality; being 'male' may be an imperfect proxy for the underlying driver of
      disease-induced mortality; or males may experience increased severity of disease
      induced effects compared with females. Here, we infer the drivers of sex-specific
      epidemiology by decomposing fixed mortality rates into mortality trajectories and
      comparing their parameters. We applied Bayesian survival trajectory analysis to a
      22-year longitudinal study of a population of badgers (Meles meles) naturally
      infected with bovine tuberculosis (bTB). At the point of infection, infected male
      and female badgers had equal mortality risk, refuting the hypothesis that
      acquisition of infection occurs in males with coincidentally high mortality.
      Males and females exhibited similar levels of heterogeneity in mortality risk,
      refuting the hypothesis that maleness is only a proxy for disease susceptibility.
      Instead, sex differences were caused by a more rapid increase in male mortality
      rates following infection. Males are indeed more susceptible to bTB, probably due
      to immunological differences between the sexes. We recommend this mortality
      trajectory approach for the study of infection in animal populations. 

PMID- 25056623
TI  - The evolution of index signals to avoid the cost of dishonesty.
AB  - Animals often convey useful information, despite a conflict of interest between
      the signaller and receiver. There are two major explanations for such 'honest'
      signalling, particularly when the size or intensity of signals reliably indicates
      the underlying quality of the signaller. Costly signalling theory (including the
      handicap principle) predicts that dishonest signals are too costly to fake,
      whereas the index hypothesis predicts that dishonest signals cannot be faked.
      Recent evidence of a highly conserved causal link between individual quality and
      signal growth appears to bolster the index hypothesis. However, it is not clear
      that this also diminishes costly signalling theory, as is often suggested. Here,
      by incorporating a mechanism of signal growth into costly signalling theory, we
      show that index signals can actually be favoured owing to the cost of dishonesty.
      We conclude that costly signalling theory provides the ultimate, adaptive
      rationale for honest signalling, whereas the index hypothesis describes one
      proximate (and potentially very general) mechanism for achieving honesty. 

PMID- 25056622
TI  - Molecular analysis of ancient caries.
AB  - An 84 base pair sequence of the Streptococcus mutans virulence factor, known as
      dextranase, has been obtained from 10 individuals from the Bronze Age to the
      Modern Era in Europe and from before and after the colonization in America.
      Modern samples show four polymorphic sites that have not been found in the
      ancient samples studied so far. The nucleotide and haplotype diversity of this
      region have increased over time, which could be reflecting the footprint of a
      population expansion. While this segment has apparently evolved according to
      neutral evolution, we have been able to detect one site that is under positive
      selection pressure both in present and past populations. This study is a first
      step to study the evolution of this microorganism, analysed using direct evidence
      obtained from ancient remains. 

PMID- 25056624
TI  - Male receiver bias for red agonistic signalling in a yellow-signalling widowbird:
      a field experiment.
AB  - Receiver bias models of signal evolution are typically regarded as alternatives
      or complements to ornament evolution due to coevolving mate choice, whereas
      sexually or socially selected agonistic signals are rarely studied with respect
      to receiver psychology. Against the background of convergent evolution of red
      agonistic signals from yellow ancestors in the genus Euplectes (widowbirds and
      bishops), we experimentally test the function of a yellow signal in the montane
      marsh widowbird (E. psammocromius), as well as a hypothesized receiver bias for
      redder (longer wavelength) hues. In a field experiment in southern Tanzania,
      males that had their yellow wing patches blackened lost their territories or lost
      territorial contests more often than controls or reddened males, which together
      with a longer wavelength hue in territory holders, indicates an agonistic signal
      function. Males painted a novel red hue, matching that of red-signalling
      congeners, retained their territories and won contests more often than controls.
      To our knowledge, this is the first demonstration of a receiver bias driving
      agonistic signal evolution. Although the sensory or cognitive origin of this bias
      is yet unknown, it strengthens our view that genetically constrained signal
      production (i.e. carotenoid metabolism), rather than differential selection,
      explains the carotenoid colour diversification in Euplectes.

PMID- 25056625
TI  - Effects of deception in social networks.
AB  - Honesty plays a crucial role in any situation where organisms exchange
      information or resources. Dishonesty can thus be expected to have damaging
      effects on social coherence if agents cannot trust the information or goods they
      receive. However, a distinction is often drawn between prosocial lies ('white'
      lies) and antisocial lying (i.e. deception for personal gain), with the former
      being considered much less destructive than the latter. We use an agent-based
      model to show that antisocial lying causes social networks to become increasingly
      fragmented. Antisocial dishonesty thus places strong constraints on the size and
      cohesion of social communities, providing a major hurdle that organisms have to
      overcome (e.g. by evolving counter-deception strategies) in order to evolve
      large, socially cohesive communities. In contrast, white lies can prove to be
      beneficial in smoothing the flow of interactions and facilitating a larger, more
      integrated network. Our results demonstrate that these group-level effects can
      arise as emergent properties of interactions at the dyadic level. The balance
      between prosocial and antisocial lies may set constraints on the structure of
      social networks, and hence the shape of society as a whole. 

PMID- 25056627
TI  - An experimental analysis of the heritability of variation in glucocorticoid
      concentrations in a wild avian population.
AB  - Glucocorticoid hormones (CORT) are predicted to promote adaptation to variable
      environments, yet little is known about the potential for CORT secretion patterns
      to respond to selection in free-living populations. We assessed the heritable
      variation underlying differences in hormonal phenotypes using a cross-foster
      experimental design with nestling North American barn swallows (Hirundo rustica
      erythrogaster). Using a bivariate animal model, we partitioned variance in
      baseline and stress-induced CORT concentrations into their additive genetic and
      rearing environment components and estimated their genetic correlation. Both
      baseline and stress-induced CORT were heritable with heritability of 0.152 and
      0.343, respectively. We found that the variation in baseline CORT was best
      explained by rearing environment, whereas the variation in stress-induced CORT
      was contributed to by a combination of genetic and environmental factors.
      Further, we did not detect a genetic correlation between these two hormonal
      traits. Although rearing environment appears to play an important role in the
      secretion of both types of CORT, our results suggest that stress-induced CORT
      levels are underlain by greater additive genetic variance compared with baseline
      CORT levels. Accordingly, we infer that the glucocorticoid response to stress has
      a greater potential for evolutionary change in response to selection compared
      with baseline glucocorticoid secretion patterns. 

PMID- 25056628
TI  - Pacific-wide contrast highlights resistance of reef calcifiers to ocean
      acidification.
AB  - Ocean acidification (OA) and its associated decline in calcium carbonate
      saturation states is one of the major threats that tropical coral reefs face this
      century. Previous studies of the effect of OA on coral reef calcifiers have
      described a wide variety of outcomes for studies using comparable partial
      pressure of CO2 (pCO2) ranges, suggesting that key questions remain unresolved.
      One unresolved hypothesis posits that heterogeneity in the response of reef
      calcifiers to high pCO2 is a result of regional-scale variation in the responses
      to OA. To test this hypothesis, we incubated two coral taxa (Pocillopora
      damicornis and massive Porites) and two calcified algae (Porolithon onkodes and
      Halimeda macroloba) under 400, 700 and 1000 MUatm pCO2 levels in experiments in
      Moorea (French Polynesia), Hawaii (USA) and Okinawa (Japan), where environmental
      conditions differ. Both corals and H. macroloba were insensitive to OA at all
      three locations, while the effects of OA on P. onkodes were location-specific. In
      Moorea and Hawaii, calcification of P. onkodes was depressed by high pCO2, but
      for specimens in Okinawa, there was no effect of OA. Using a study of large
      geographical scale, we show that resistance to OA of some reef species is a
      constitutive character expressed across the Pacific. 

PMID- 25056629
TI  - Bioactive cembrane derivatives from the Indian Ocean soft coral, Sinularia
      kavarattiensis.
AB  - Marine organisms and their metabolites represent a unique source of potential
      pharmaceutical substances. In this study, we examined marine-derived substances
      for their bioactive properties in a cell-based Chikungunya virus (CHIKV) replicon
      model and for in vitro anti-inflammatory activity. In the screening of a marine
      sample library, crude extracts from the Indian soft coral, Sinularia
      kavarattiensis, showed promising activity against the CHIKV replicon. Bioassay
      guided chemical fractionation of S. kavarattiensis resulted in the isolation of
      six known norcembranoids (1-6) and one new compound, named kavaranolide (7). The
      structures were elucidated on the basis of NMR and MS spectroscopic data.
      Compounds 1-3 and 5-7 were evaluated for their replicon-inhibiting potential in
      the CHIKV model by using a luminescence-based detection technique and live cell
      imaging. Compounds 1 and 2 showed moderate inhibition of the CHIKV replicon, but
      imaging studies also revealed cytotoxic properties. Moreover, the effects of the
      isolated compounds on primary microglial cells, an experimental model for
      neuroinflammation, were evaluated. Compound 2 was shown to modulate the immune
      response in microglial cells and to possess potential anti-inflammatory
      properties by dose-dependently reducing the release of pro- and anti-inflammatory
      cytokines. 

PMID- 25056630
TI  - Understanding nanocalcification: a role suggested for crystal ghosts.
AB  - The present survey deals with the initial stage of the calcification process in
      bone and other hard tissues, with special reference to the organic-inorganic
      relationship and the transformation that the early inorganic particles undergo as
      the process moves towards completion. Electron microscope studies clearly exclude
      the possibility that these particles might be crystalline structures, as often
      believed, by showing that they are, instead, organic-inorganic hybrids, each
      comprising a filamentous organic component (the crystal ghost) made up of acidic
      proteins. The hypothesis is suggested that the crystal ghosts bind and stabilize
      amorphous calcium phosphate and that their subsequent degradation allows the
      calcium phosphate, once released, to acquire a hydroxyapatite, crystal-like
      organization. A conclusive view of the mechanism of biological calcification
      cannot yet be proposed; even so, however, the role of crystal ghosts as a
      template of the structures usually called "crystallites" is a concept that has
      gathered increasing support and can no longer be disregarded. 

PMID- 25056631
TI  - Dolabelladienols A-C, new diterpenes isolated from Brazilian brown alga Dictyota
      pfaffii.
AB  - The marine brown alga Dictyota pfaffii from Atol das Rocas, in Northeast Brazil
      is a rich source of dolabellane diterpene, which has the potential to be used in
      future antiviral drugs by inhibiting reverse transcriptase (RT) of HIV-1.
      Reexamination of the minor diterpene constituents yielded three new dolabellane
      diterpenes, (1R*,2E,4R*,7S,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)
      dolabelladiene (1), (1R*,2E,4R*,7R*,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy
      2,8(17)-dolabelladiene (2), (1R*,2E,4R*,8E,10S*,11S,12R*)10,18-diacetoxy-7
      hydroxy-2,8-dolabelladiene (3), termed dolabelladienols A-C (1-3) respectively,
      in addition to the known dolabellane diterpenes (4-6). The elucidation of the
      compounds 1-3 was assigned by 1D and 2D NMR, MS, optical rotation and molecular
      modeling, along with the relative configuration of compound 4 and the absolute
      configuration of 5 by X-ray diffraction. The potent anti-HIV-1 activities
      displayed by compounds 1 and 2 (IC50 = 2.9 and 4.1 MUM), which were more active
      than even the known dolabelladienetriol 4, and the low cytotoxic activity against
      MT-2 lymphocyte tumor cells indicated that these compounds are promising anti-HIV
      1 agents. 

PMID- 25056632
TI  - Recognition of LPS by TLR4: potential for anti-inflammatory therapies.
AB  - LPS molecules of marine bacteria show structures distinct from terrestrial
      bacteria, due to the different environment that marine bacteria live in. Because
      of these different structures, lipid A molecules from marine bacteria are most
      often poor stimulators of the Toll-like receptor 4 (TLR4) pathway. Due to their
      low stimulatory potential, these lipid A molecules are suggested to be applicable
      as antagonists of TLR4 signaling in sepsis patients, where this immune response
      is amplified and unregulated. Antagonizing lipid A molecules might be used for
      future therapies against sepsis, therapies that currently do not exist. In this
      review, we will discuss these differences in lipid A structures and their
      recognition by the immune system. The modifications present in marine lipid A
      structures are described, and their potential as LPS antagonists will be
      discussed. Finally, since clinical trials built on antagonizing lipid A molecules
      have proven unsuccessful, we propose to also focus on different aspects of the
      TLR4 signaling pathway when searching for new potential drugs. Furthermore, we
      put forward the notion that bacteria probably already produce inhibitors of TLR4
      signaling, making these bacterial products interesting molecules to investigate
      for future sepsis therapies. 

PMID- 25056633
TI  - Intraoperative portable CT-scanner based spinal navigation--a feasibility and
      safety study.
AB  - BACKGROUND: Navigation based on an intraoperative CT scan is not a new approach
      to spinal instrumentation. Innovative intraoperative imaging technology, however,
      opens new horizons to more precise image acquisition as well as to further
      workflow. Planning of screw entry-points and trajectories in this study had been
      based on intraoperative imaging obtained by a portable 32-slice CT scanner. This
      prospective study evaluates feasibility, accuracy, and safety of this novel
      approach in an initial series of 85 surgeries. METHOD: Medical records and
      radiological materials of 82 patients who underwent the first 85 consecutive
      stabilisations were analysed. Incorrect screw position, medical and technical
      complications as well as availability of this procedure in particular spinal
      levels were the subject of evaluation. RESULTS: Out of 571 implants inserted in
      all spinal levels, only five screws (0.87 %) did not meet the criteria for
      correct implant position. These screw misplacements had not been complicated by
      neural, vascular or visceral injury and the surgeon was not forced to change the
      position intraoperatively or during the postoperative period. The quality of
      intraoperative CT imaging sufficient for navigation was obtained at all spinal
      segments regardless of a patient's habitus or positioning or comorbidity.
      CONCLUSION: Intraoperative portable CT scanner-based navigation seems to be an
      effective way of doing spinal instrumentation guidance. High precision of implant
      insertion confirms the preconditions of navigation usage during more complex
      surgeries at any level of the spine.

PMID- 25056634
TI  - Assessment of aortitis by semiquantitative analysis of 180-min 18F-FDG PET/CT
      acquisition images.
AB  - PURPOSE: The aim of this study was to evaluate the contribution of
      semiquantitative analysis of 180-min (18)F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET)/CT images for the assessment of aortitis in cases of
      suspected large vessel vasculitis (LVV) and to establish a threshold index for
      application in the clinical setting. METHODS: This prospective study included 43
      patients (mean age 67.5 +/- 12.9 years) with suspicion of LVV (25 with a final
      diagnosis of aortitis). (18)F-FDG PET/CT scan was acquired 180 min after
      injection of 7 MBq/kg of (18)F-FDG. A semiquantitative analysis was performed
      calculating the aortic wall maximum standardized uptake value (SUVmax) (T), the
      lumen SUVmax (B) and the target to background ratio (TBR). These results were
      also compared with those obtained in a control population. RESULTS: The mean
      aortic wall SUVmax was 2.00 +/- 0.62 for patients with aortitis and 1.45 +/- 0.31
      for patients without aortitis (p < 0.0001). The TBR was 1.66 +/- 0.26 for
      patients with aortitis and 1.24 +/- 0.08 for patients without aortitis (p <
      0.0001). The differences were also statistically significant when the patients
      with aortitis and controls were compared. Receiver-operating characteristic (ROC)
      analysis revealed that the area under the curve was greater for the TBR than for
      the aortic wall SUVmax (0.997 vs 0.871). The highest sensitivity and specificity
      was obtained for a TBR of 1.34 (sensitivity 100%, specificity 94.4%). CONCLUSION:
      Semiquantitative analysis of PET/CT images acquired 180 min after (18)F-FDG
      injection and the TBR index of 1.34 show very high accuracy and, therefore, are
      strongly recommended for the diagnosis of aortitis in the clinical setting.

PMID- 25056635
TI  - [Challenges in inpatient ophthalmology for elderly patients].
AB  - PURPOSE: The demographic changes will lead to an increase in elderly patients in
      the field of medicine and in particular ophthalmology. The purpose of this study
      was to assess ocular problems of inpatients in the clinical setting with a focus
      on patients over 60 years old, especially elderly patients over 80 years and very
      old patients over 90 years. METHODS: All consecutive inpatients were included in
      the study. Medical data were analyzed concerning the diagnosis, operative
      indications and comorbidities and the presence of dementia disorders was also
      considered. The effects of age or diseases on the inpatient course were
      investigated. RESULTS: At the eye clinic in Frankfurt (Oder) the mean age of
      patients was 69 years and was the highest of all medical and surgical
      disciplines. The age of patients of internal medicine was similarly with 67 years
      but orthopedic and urological patients were on average 64 years old. In the other
      departments the mean age of patients was clearly less than 60 years old. Of the
      patients 26% were aged 80 years or older. A total of 31 patients over 90 years
      old were treated as inpatients (2.0%) during the year 2012. The treatment
      relevant diagnosis increased with age. Nearly 40% had a reduced mobility at an
      age of 80-89 years and 60% at an age over 90 years. In the age group over 90
      years approximately 25% had dementia and 20% a visual disorder. CONCLUSION: Old
      and very old patients with ocular problems and more than 80-90 years of age had
      an increased comorbidity concerning the relevant treatment diagnostics. This has
      relevant implications and challenges for nursing and medical care in the clinical
      setting.

PMID- 25056637
TI  - A chemo-mechanical switch for controllable water transportation based on a
      thermally responsive block copolymer.
AB  - A smart and reversible chemo-mechanical switch was developed by synthesis of a
      thermally responsive block copolymer brush poly(N-isopropylacrylamide-co
      hexafluoroisopropyl acrylate) (P(NIPAAm-co-HFIPA)) on a capillary plate. With the
      temperature changing around lower critical solution temperature (LCST), the
      designed chemo-mechanical switch exhibited excellent "ON-OFF" behavior for water
      transportation. 

PMID- 25056638
TI  - Positive effect of the yellow morph on female reproductive success in the flower
      colour polymorphic Iris lutescens (Iridaceae), a deceptive species.
AB  - The deceptive Iris lutescens (Iridaceae) shows a heritable and striking flower
      colour polymorphism, with both yellow- and purple-flowered individuals growing
      sympatrically. Deceptive species with flower colour polymorphism are mainly
      described in the family Orchidaceae and rarely found in other families. To
      explain the maintenance of flower colour polymorphism in I. lutescens, we
      investigated female reproductive success in natural populations of southern
      France, at both population and local scales (within populations). Female
      reproductive success was positively correlated with yellow morph frequency, at
      both the population scale and the local scale. Therefore, we failed to observe
      negative frequency-dependent selection (NFDS), a mechanism commonly invoked to
      explain flower colour polymorphism in deceptive plant species. Flower size and
      local flower density could also affect female reproductive success in natural
      populations. Pollinator behaviour could explain the positive effect of the yellow
      morph, and our results suggest that flower colour polymorphism might not persist
      in I. lutescens, but alternative explanations not linked to pollinator behaviour
      are discussed. In particular, NFDS, although an appealingly simple explanation
      previously demonstrated in orchids, may not always contribute to maintaining
      flower colour polymorphism, even in deceptive species. 

PMID- 25056639
TI  - Real-time handheld emission spot allocator (rthESA) for simultaneous fusion
      imaging with ultrasound.
AB  - OBJECTIVES: First, to report on initial experiences and technical parameters of a
      newly developed real-time handheld emission spot allocator (rthESA), and second,
      to report on the simultaneous acquisition of rthESA and US data as rthESA/US
      fusion images. METHODS: The rthESA consisted of five semiconductor-detectors
      arranged in alternate position in two rows. This design allowed the examination
      of focal activities in the same plane as US. The signals were interpreted by an
      ad hoc software and the real-time allocation of spot radiation sources within air
      and water phantoms was investigated for (99m)Tc, 131I, and 18F. A compact US
      probe was fixed in plane with the rthESA and connected to a standard US
      equipment. Experiments with a liver phantom were performed to verify the
      integration of (99m)Tc-rthESA data and US images. RESULTS: The allocation proved
      to be successful for all radionuclides. The system showed a noticeable
      performance latency, most pronounced for positions far from the detector (1 cm
      distance: 0.7 +/- 0.5 s; 4 cm distance: 6.1 +/- 3.2 s). Within the liver phantom,
      the rthESA enabled the correct allocation of a spot radiation source within a
      live US image. CONCLUSIONS: The rthESA allowed an exact localization of spot
      radiation sources in single plane, with additional consideration of the distance
      from the detector, leading to real-time allocation and simultaneous overlay with
      US images. In spite of clear technical limitations in need of further
      development, this proof-of-concept study shows that this hybrid detector has the
      potential to provide integrated simultaneous nuclear medicine and US images.

PMID- 25056640
TI  - Toward four-dimensional image-guided adaptive brachytherapy in locally recurrent
      endometrial cancer.
AB  - PURPOSE: To evaluate clinical outcome and feasibility of a four-dimensional image
      guided adaptive brachytherapy concept in patients with locally recurrent
      endometrial cancer. METHODS AND MATERIALS: Forty-three patients with locally
      recurrent endometrial cancer were included. Treatment consisted of conformal
      external beam radiotherapy followed by a boost using pulsed-dose-rate
      brachytherapy (BT). Large tumors were treated with MRI-guided interstitial BT.
      Small tumors were treated with CT-guided intracavitary BT. The planning aim
      (total external beam radiotherapy and BT) for high-risk clinical target volume
      was D90 > 80 Gy, whereas constraints for organs at risk were D2cc <= 90 Gy for
      bladder and D2cc <= 70 Gy for rectum, sigmoid, and bowel in terms of equivalent
      dose in 2 Gy fractions. RESULTS: Median high-risk clinical target volume was 18
      cm(3) (range, 0-91). D90 was 82 Gy (range, 77-88). D2cc to bladder, rectum, and
      sigmoid were 67 Gy (range, 50-81), 67 Gy (range, 51-77), and 55 Gy (range, 44
      68), respectively. Median followup was 30 months (6-88). Two-year local control
      rate was 92% (standard error [SE], 5). Disease-free survival rate and overall
      survival rate was 59% (SE, 8) and 78% (SE, 7), respectively. Patients with low-
      to intermediate-risk for recurrence had a 2-year disease-free survival rate of
      72% (SE, 9) compared with 42% (SE, 12) in patients with high risk for recurrence
      (p = 0.04). Late morbidity Grade 3 was recorded in 5 (12%) patients. CONCLUSIONS:
      Four-dimensional image-guided adaptive brachytherapy is feasible in locally
      recurrent endometrial cancer. Local control rate is good. Systemic control
      remains a problem in patients with high risk for recurrence.

PMID- 25056641
TI  - High-dose proton beam therapy for sinonasal mucosal malignant melanoma.
AB  - BACKGROUND: The significance of definitive radiotherapy for sinonasal mucosal
      melanoma (SMM) is sill controvertial. This study was to evaluate the role of high
      dose proton beam therapy (PBT) in patients with SMM. METHODS: The cases of 20
      patients with SMM localized to the primary site who were treated by PBT between
      2006 and 2012 were retrospectively analyzed. The patterns of overall survival and
      morbidity were assessed. RESULTS: The median follow-up time was 35 months (range,
      6-77 months). The 5-year overall and disease-free survival rates were 51% and
      38%, respectively. Four patients showed local failure, 2 showed regrowth of the
      primary tumor, and 2 showed new sinonasal tumors beyond the primary site. The 5
      year local control rate after PBT was 62%. Nodal and distant failure was seen in
      7 patients. Three grade 4 late toxicities were observed in tumor-involved optic
      nerve. CONCLUSION: Our findings suggested that high-dose PBT is an effective
      local treatment that is less invasive than surgery but with comparable outcomes.

PMID- 25056642
TI  - Enhancing dye-sensitized solar cell performances by molecular engineering: highly
      efficient pi-extended organic sensitizers.
AB  - This study deals with the synthesis and characterization of two pi-extended
      organic sensitizers (G1 and G2) for applications in dye-sensitized solar cells.
      The materials are designed with a D-A-pi-A structure constituted by i) a
      triarylamine group as the donor part, ii) a dithienyl-benzothiadiazole
      chromophore followed by iii) a further ethynylene-thiophene (G1) or ethynylene
      benzene (G2) pi-spacer and iv) a cyano-acrylic moiety as acceptor and anchoring
      part. An unusual structural extension of the pi-bridge characterizes these
      structures. The so-configured sensitizers exhibit a broad absorption profile, the
      origin of which is supported by density functional theory. The absence of
      hypsochromic shifts as a consequence of deprotonation as well as notable optical
      and electrochemical stabilities are also observed. Concerning the performances in
      devices, electrochemical impedance spectroscopy indicates that the structural
      modification of the pi-spacer mainly increases the electron lifetime of G2 with
      respect to G1. In devices, this feature translates into a superior power
      conversion efficiency of G2, reaching 8.1%. These results are comparable to those
      recorded for N719 and are higher with respect to literature congeners, supporting
      further structural engineering of the pi-bridge extension in the search for
      better performing pi-extended organic sensitizers.

PMID- 25056644
TI  - [Modifications and new aspects pertaining to electronic hearing implants].

PMID- 25056643
TI  - Hypersensitivity to chemotherapeutics: a cross sectional study with 35
      desensitisations.
AB  - BACKGROUND: Chemotherapy is one of the main treatments for lung cancer, and in
      these patients, discontinuation of treatment due to uncontrollable
      hypersensitivity reactions (HSRs) is an important problem. AIM: To determine the
      frequency of HSRs during chemotherapy and to review current approaches. METHODS:
      We did a cross sectional study in patients undergoing chemotherapy for lung
      cancer in a reference chemotherapy unit from January 2012 to January 2013.
      Patients who developed immediate-HSRs or delayed-HSRs to chemotherapeutics and
      gave consent were included into study. The effectiveness of a standardised 12
      step "rapid drug desensitisation" (RDD) procedure was investigated in patients
      with immediate-HSRs. RESULTS: In total, 1,099 cycles of chemotherapy were
      administered to 292 patients in 1 year. We observed ten HSRs, during ten cycles
      in ten patients (~3 % of the patients). Two HSRs were delayed-type, eight were
      immediate-type at grade 1-3. Of those with immediate-type HSR, five patients with
      grade 2-3, and additional two referred patients with grade 4 HSRs were
      successfully given their culprit drug in 35 cycles of chemotherapy with 12-step
      or modified 20-step RDD protocol. CONCLUSIONS: HSRs to chemotherapeutics are not
      so rare. Premedication alone does not prevent such reactions. The results of RDD
      treatment look promising for continuing treatment with the culprit
      chemotherapeutic agent.

PMID- 25056645
TI  - [Direct acoustic cochlear stimulation for therapy of severe to profound mixed
      hearing loss: CodacsTM Direct Acoustic Cochlear Implant System].
AB  - OBJECTIVE: Implantable hearing aids have become a valid option for the therapy of
      various forms of hearing loss. The CodacsTM Direct Acoustic Cochlear Implant
      System is the first vibratory implant available for patients with severe to
      profound mixed hearing loss (MHL). By directly coupling sound energy into the
      perilymph, a very high maximum power output (MPO) is achieved over a broad
      frequency range. Via a conventional stapedotomy, the vibratory energy of the
      electromagnetic actuator is transferred directly to the perilymph through the
      oval window. PATIENTS AND METHODS: This article describes the technical
      principle, basic surgical aspects and audiological outcomes of two clinical
      studies. Additional coupling procedures and extensions to the spectrum of
      indications are also discussed. Surgically, the two-component system can either
      be implanted via a purely transmastoid approach with posterior tympanotomy, or
      additionally via transmeatal access to the stapes footplate. Pre- and
      postoperative audiological results of patients wearing conventional hearing aids
      and with severe to profound MHL, who were implanted with the CodacsTM system at
      the Medical University Hannover, were compared. RESULTS: Significant improvements
      over conventional hearing aids could be achieved with initial bone conduction
      thresholds between 44 and 63 dB HL (O 54 dB HL) and an air-bone gap between 19
      and 51 dB HL (O 34 dB HL) in patients with MHL caused by advanced otosclerosis or
      tympanosclerosis and an intact posterior wall of the auditory canal. The mean
      functional gain was 50 +/- 9 dB (0.5-4 kHz) and the monosyllabic word score was
      85% at 65 dB presentation level compared to conventional hearingaids with 25%.
      Speech intelligibility in noise (S0N0) improved by 7.1 to O 0.3 dB SNR with
      CodacsTM. The mean bone conduction threshold remained unchanged or showed a
      minimal increase in the low-frequency range. CONCLUSION: The CODACS system
      provides an effective new treatment for patients with severe to profound MHL for
      the first time.

PMID- 25056646
TI  - [A fully-implantable active hearing device in congenital auricular atresia].
AB  - Active implantable hearing devices were primarily developed for sensorineural
      hearing loss. The vibrator coupling mechanisms were oriented towards normal
      middle ear anatomy and function. The aim of this project was to modify the only
      fully implantable hearing device with an implantable microphone for application
      in congenital auricular atresia, CarinaTM, and to introduce the modified device
      into the clinic. A special prosthesis was developed for the transducer and its
      individual coupling achieved by a special cramping system. The system was
      implanted in 5 patients with congenital auricular atresia. Audiological results
      were good; with patients' hearing gain exceeding 30 dB HL. Anatomic limits to the
      system's indications and technical drawbacks are also discussed.

PMID- 25056647
TI  - [Semi-implantable transcutaneous bone conduction hearing devices].
AB  - BACKGROUND: Patients with air-bone gaps or combined hearing loss that cannot be
      corrected by tympanoplasty can be treated with bone conduction hearing aids. The
      disadvantages of conventional and percutaneous systems are, on one hand, the
      obvious external fixation components and on the other hand, the biological and
      psychosocial problems of open implants. This project was therefore set up to
      develop a semi-implantable, magnetically anchored transcutaneous bone conduction
      device, introduce it into clinical application and follow-up the results.
      PATIENTS AND METHODS: The principle of this bone conduction device is the
      magnetic coupling of an external vibrator via implanted double magnets. After
      extensive laboratory tests, this method was introduced into the clinic in 2006.
      Following the initial pilot study, 184 implantations in 143 patients have been
      performed in Recklinghausen since 2008. Long-term evaluation of 20 congenital
      atresia patients treated with these devices was possible. RESULTS: Worldwide,
      more than 3000 of these devices have been implanted. The operative implantation
      technique is relatively simple. With the new "upside down technique", bone
      removal is no longer necessary. The 2.6-mm thin implants are hardly noticeable.
      The hearing improvement is similar to that of other bone conduction hearing aids.
      CONCLUSION: This semi-implantable transcutaneous bone conduction hearing device
      is another option for patients with air-bone gaps, combined hearing loss or
      single-sided deafness.

PMID- 25056649
TI  - [An unusual cervical tumor].

PMID- 25056648
TI  - [The Vibrant Soundbridge as an active implant in middle ear surgery].
AB  - Implantable hearing aids are not only gaining importance for the treatment of
      sensorineural hearing loss, but also for treatment of mixed hearing loss. The
      most frequently used active middle ear implant is the Vibrant Soundbridge (VSB)
      system (Fa. MED-EL, Innsbruck, Osterrreich). Following widening of the spectrum
      of indications for the VBS, various new coupling systems have been established.
      Based on the literature, available petrosal bone investigations and finite
      element model (FEM) calculations, this article summarizes the current knowledge
      concerning mechanical excitation by the VSB. Important concomitant aspects
      related to coupling, transmission and measurement are also discussed.

PMID- 25056650
TI  - [Hoarseness: biomechanisms and quantitative laryngoscopy].
AB  - Every phonosurgical procedure alters endolaryngeal anatomy; be it by removing
      tissue, or injection or implantation of autologous or foreign material. However,
      the effect that an altered airflow cross section and changed soft tissue
      elasticity will have on the voice cannot be predicted. With the aim of promoting
      rational indications for phonosurgery, the current article explains the
      biomechanisms of the normal and the disordered voice, including the complex
      interdependence of tissue viscoelasticity, glottal airstream and sound
      production. According to European Laryngological Society (ELS) recommendations,
      five - not entirely mutually independent - evaluation criteria form the basis of
      indication assessments: self-rating (by the patient), proxy rating (by the
      physician), technical signal analysis (computerized), aerodynamics (spirometry)
      and vibration analysis (stroboscopy). The ELS evaluation standards agreed upon in
      2001 enable indications and - by virtue of pre- and postoperative comparisons -
      therapeutic successes to be assessed. The 10-year-old ELS protocol has been
      updated by a real-time method for visualizing vocal fold vibrations: the
      phonovibrogram (PVG) has replaced stroboscopy. Independently of the morphological
      anatomic details of the larynx, PVG visualizes the symmetry and regularity of
      vocal fold motion, thus allowing preoperative estimation of tissue elasticity. 

PMID- 25056651
TI  - The pathway to grandparenting stress: trauma, relational conflict, and emotional
      well-being.
AB  - OBJECTIVES: This paper examines the mediating effect of child-grandparent
      conflict on the relationship between child trauma exposure and grandparenting
      stress. METHODS: Data was collected from a sample of custodial grandparents who
      participated in kinship care or relative caregiving programs (n = 251).
      Grandparenting stress was measured with Parenting Stress Scale (Berry & Jones,
      1995 ) modified for grandparents. A series of regression models and structural
      equation models (SEM) were used to test the relationship between the number of
      different types of child trauma exposures and grandparenting stress, and to
      examine the mediating effect of child-grandparent conflicts on the relationship.
      RESULTS: Almost three-fourths (72%) of children had experienced at least one type
      of traumatic exposure. The SEM model shows that child's trauma exposure
      indirectly affected grandparenting stress, mediated by child-grandparenting
      conflicts though no direct path between the child's trauma exposure variable and
      grandparenting stress was found. A higher level of child-grandparent conflicts
      was also associated with a lower level of emotional well-being among custodial
      grandparents. CONCLUSION: Based on these findings, recommendations are made about
      how to tailor a trauma-informed approach to the needs of custodial grandparents.

PMID- 25056654
TI  - Role of zinc interstitials and oxygen vacancies of ZnO in photocatalysis: a
      bottom-up approach to control defect density.
AB  - Oxygen vacancies (V(O)s) in ZnO are well-known to enhance photocatalytic activity
      (PCA) despite various other intrinsic crystal defects. In this study, we aim to
      elucidate the effect of zinc interstitials (Zn(i)) and V(O)s on PCA, which has
      applied as well as fundamental interest. To achieve this, the major hurdle of
      fabricating ZnO with controlled defect density requires to be overcome, where it
      is acknowledged that defect level control in ZnO is significantly difficult. In
      the present context, we fabricated nanostructures and thoroughly characterized
      their morphological (SEM, TEM), structural (XRD, TEM), chemical (XPS) and optical
      (photoluminescence, PL) properties. To fabricate the nanostructures, we adopted
      atomic layer deposition (ALD), which is a powerful bottom-up approach. However,
      to control defects, we chose polysulfone electrospun nanofibers as a substrate on
      which the non-uniform adsorption of ALD precursors is inevitable because of the
      differences in the hydrophilic nature of the functional groups. For the first 100
      cycles, Zn(i)s were predominant in ZnO quantum dots (QDs), while the presence of
      V(O)s was negligible. As the ALD cycle number increased, V(O)s were introduced,
      whereas the density of Zn(i) remained unchanged. We employed PL spectra to
      identify and quantify the density of each defect for all the samples. PCA was
      performed on all the samples, and the percent change in the decay constant for
      each sample was juxtaposed with the relative densities of Zn(i)s and V(O)s. A
      logical comparison of the relative defect densities of Zn(i)s and V(O)s suggested
      that the former are less efficient than the latter because of the differences in
      the intrinsic nature and the physical accessibility of the defects. Other reasons
      for the efficiency differences were elaborated.

PMID- 25056653
TI  - Cabozantinib: a review of its use in patients with medullary thyroid cancer.
AB  - Cabozantinib (Cometriq((r))) is an orally administered small molecule inhibitor
      of multiple tyrosine kinase receptors, including those involved in the
      pathogenesis of medullary thyroid cancer (MTC) [i.e. rearranged during
      transfection (RET), MET and vascular endothelial growth factor receptor (VEGFR)
      2]. Cabozantinib is indicated for the treatment of adults with progressive,
      unresectable locally advanced (in the EU) or metastatic (in the EU and USA) MTC.
      Compared with placebo, cabozantinib significantly prolonged progression-free
      survival, reflecting a 72% reduction in the risk of disease progression or death,
      in patients with unresectable, locally advanced or metastatic MTC participating
      in a multinational, phase III study. A significantly higher proportion of
      patients receiving cabozantinib than those receiving placebo achieved an
      objective response or disease stabilization (i.e. a complete or partial response,
      or stable disease). The overall survival benefit with cabozantinib is as yet
      unclear, with no significant benefit observed in two interim analyses (one
      prespecified, and one unplanned and conducted at the request of the US FDA). The
      tolerability profile of oral cabozantinib is typical for a small molecule
      targeting the VEGFR and other tyrosine kinase-mediated pathways, with adverse
      events associated with the inhibition of the VEGF pathway (e.g. gastrointestinal
      perforation, haemorrhage, hypertension and venous thrombosis) reported in the
      phase III study. Treatment-emergent adverse events were generally managed with
      supportive therapy, dose reductions and/or dose interruptions. Although final
      overall survival data are awaited, current evidence suggests cabozantinib to be a
      valuable treatment option for adults with progressive, unresectable locally
      advanced or metastatic MTC.

PMID- 25056655
TI  - Effect of yogurt containing polydextrose, Lactobacillus acidophilus NCFM and
      Bifidobacterium lactis HN019: a randomized, double-blind, controlled study in
      chronic constipation.
AB  - BACKGROUND: Constipation is a frequent complaint and the combination of a
      prebiotic and probiotics could have a potentially synergic effect on the
      intestinal transit. The present study therefore aims to investigate the
      combination of polydextrose (Litesse), L. acidophilus NCFM(r) and B. lactis HN019
      in a yogurt on intestinal transit in subjects who suffer from constipation.
      METHODS: Patients with constipation were randomly divided into two groups,
      Control Group (CG) and Treatment Group (TG), and had to eat 180 ml of unflavored
      yogurt every morning for 14 days. Those in the CG received only yogurt, while the
      TG received yogurt containing polydextrose, L. acidophilus NCFM (ATCC 700396) and
      B. lactis HN019 (AGAL NM97/09513). RESULTS: Favourable clinical response was
      assessed since Agachan score had a significant reduction at the end of the study
      in both groups and tended to be better in the TG. The subjects in the treatment
      group also had a shorter transit time at the end of the intervention compared to
      the control group (p = 0.01). CONCLUSION: The product containing yogurt with
      polydextrose, B. lactis HN019 and L. acidophilus NCFM(r) significantly shortened
      colonic transit time after two weeks in the TG compared to CG and may be an
      option for treatment of constipation.

PMID- 25056656
TI  - Osteopontin: a new player in regulating hepatic ductular reaction and hepatic
      progenitor cell responses during chronic liver injury.

PMID- 25056657
TI  - Authors' response: bile acids are important in the pathophysiology of IBS.

PMID- 25056658
TI  - Salivary pepsin to diagnose GORD?

PMID- 25056652
TI  - Asthma therapy and its effect on airway remodelling.
AB  - Asthma remains a major health problem with significant morbidity, mortality and
      economic costs. In asthma, airway remodelling, which refers to all the
      microscopic structural changes seen in the airway tissue, has been recognised for
      many decades and remains one of the defining characteristics of the disease;
      however, it is still poorly understood. The detrimental pathophysiological
      consequences of some features of remodelling, like increased airway smooth muscle
      mass and subepithelial fibrosis, are well documented. However, whether targeting
      these by therapy would be beneficial is unknown. Although the prevailing thinking
      is that remodelling is an abnormal response to persistent airway inflammation,
      recent evidence, especially from studies of remodelling in asthmatic children,
      suggests that the two processes occur in parallel. The effects of asthma therapy
      on airway remodelling have not been studied extensively due to the challenges of
      obtaining airway tissue in the context of clinical trials. Corticosteroids remain
      the cornerstone of asthma therapy, and their effects on remodelling have been
      better studied than other drugs. Bronchial thermoplasty is the only asthma
      therapy to primarily target remodelling, although how it results in the apparent
      clinical benefits seen is not exactly clear. In this article we discuss the
      mechanisms of airway remodelling in asthma and review the effects of conventional
      and novel asthma therapies on the process. 

PMID- 25056659
TI  - Human buccal epithelium acquires microbial hyporesponsiveness at birth, a role
      for secretory leukocyte protease inhibitor.
AB  - OBJECTIVE: Repetitive interaction with microbial stimuli renders epithelial cells
      (ECs) hyporesponsive to microbial stimulation. Previously, we have reported that
      buccal ECs from a subset of paediatric patients with Crohn's disease are not
      hyporesponsive and spontaneously released chemokines. We now aimed to identify
      kinetics and mechanisms of acquisition of hyporesponsiveness to microbial
      stimulation using primary human buccal epithelium. DESIGN: Buccal ECs collected
      directly after birth and in later stages of life were investigated. Chemokine
      release and regulatory signalling pathways were studied using primary buccal ECs
      and the buccal EC line TR146. Findings were extended to the intestinal mucosa
      using murine model systems. RESULTS: Directly after birth, primary human buccal
      ECs spontaneously produced the chemokine CXCL-8 and were responsive to microbial
      stimuli. Within the first weeks of life, these ECs attained hyporesponsiveness,
      associated with inactivation of the NF-kappaB pathway and upregulation of the
      novel NF-kappaB inhibitor SLPI but no other known NF-kappaB inhibitors. SLPI
      protein was abundant in the cytoplasm and the nucleus of hyporesponsive buccal
      ECs. Knock-down of SLPI in TR146-buccal ECs induced loss of hyporesponsiveness
      with increased NF-kappaB activation and subsequent chemokine release. This
      regulatory mechanism extended to the intestine, as colonisation of germfree mice
      elicited SLPI expression in small intestine and colon. Moreover, SLPI-deficient
      mice had increased chemokine expression in small intestinal and colonic ECs.
      CONCLUSIONS: We identify SLPI as a new player in acquisition of microbial
      hyporesponsiveness by buccal and intestinal epithelium in the first weeks after
      microbial colonisation.

PMID- 25056660
TI  - Linguistic validation of the English version of the Core Lower Urinary Tract
      Symptom Score.

PMID- 25056662
TI  - para-Quinodimethane-bridged perylene dimers and pericondensed quaterrylenes: the
      effect of the fusion mode on the ground states and physical properties.
AB  - Polycyclic hydrocarbon compounds with a singlet biradical ground state show
      unique physical properties and promising material applications; therefore, it is
      important to understand the fundamental structure/biradical character/physical
      properties relationships. In this study, para-quinodimethane (p-QDM)-bridged
      quinoidal perylene dimers 4 and 5 with different fusion modes and their
      corresponding aromatic counterparts, the pericondensed quaterrylenes 6 and 7,
      were synthesized. Their ground-state electronic structures and physical
      properties were studied by using various experiments assisted with DFT
      calculations. The proaromatic p-QDM-bridged perylene monoimide dimer 4 has a
      singlet biradical ground state with a small singlet/triplet energy gap (-2.97
      kcal mol(-1)), whereas the antiaromatic s-indacene-bridged N-annulated perylene
      dimer 5 exists as a closed-shell quinoid with an obvious intramolecular charge
      transfer character. Both of these dimers showed shorter singlet excited-state
      lifetimes, larger two-photon-absorption cross sections, and smaller energy gaps
      than the corresponding aromatic quaterrylene derivatives 6 and 7, respectively.
      Our studies revealed how the fusion mode and aromaticity affect the ground state
      and, consequently, the photophysical properties and electronic properties of a
      series of extended polycyclic hydrocarbon compounds.

PMID- 25056663
TI  - Reconstruction of perineoscrotal defects in Fournier's gangrene with pedicle
      anterolateral thigh perforator flap.
AB  - BACKGROUND: Fournier's gangrene is an acute and potentially lethal necrotizing
      fasciitis that involves the scrotum and perineum. This disease can result in the
      extensive loss of skin and soft tissues of the perineoscrotal area with exposure
      of the testes. To reconstruct the large defects of scrotal and perineal remains a
      surgical challenge. METHODS: Between January 2008 and December 2012, 26 patients
      were admitted with a diagnosis of Fournier's gangrene. The Division of Plastic
      and Reconstructive Surgery at our hospital was consulted about patients who
      needed reconstructive procedures after initial debridement was performed in the
      Division of Colorectal Surgery or the Division of Urology. Of the 26 patients, 10
      patients with large perineoscrotal defects who underwent the reconstructive
      surgery using pedicle anterolateral thigh (ALT) perforator flaps were enrolled in
      this series. RESULTS: We carried out the perineoscrotal reconstruction in these
      10 patients using the pedicled ALT perforator flaps. They were all male with a
      mean age of 59.1 years (ranged from 39 to 82 years). The size of the flaps ranged
      from 72 to 198 cm2 . All flaps survived completely but one hematoma was noticed
      postoperatively. All patients mobilized well with no limitation of motion, and
      the scrotal contour appeared to be natural. CONCLUSION: Early debridement and
      wound coverage in Fournier's gangrene are mandatory to allow patients to return
      to normal life. Pedicle ALT perforator flaps provide pliable and reliable soft
      tissue coverage for large perineoscrotal defects with adequate contour that
      result in satisfactory function and cosmesis.

PMID- 25056661
TI  - The structural network of Interleukin-10 and its implications in inflammation and
      cancer.
AB  - BACKGROUND: Inflammation has significant roles in all phases of tumor
      development, including initiation, progression and metastasis. Interleukin-10 (IL
      10) is a well-known immuno-modulatory cytokine with an anti-inflammatory
      activity. Lack of IL-10 allows induction of pro-inflammatory cytokines and
      hinders anti-tumor immunity, thereby favoring tumor growth. The IL-10 network is
      among the most important paths linking cancer and inflammation. The simple node
      and-edge network representation is useful, but limited, hampering the
      understanding of the mechanistic details of signaling pathways. Structural
      networks complete the missing parts, and provide details. The IL-10 structural
      network may shed light on the mechanisms through which disease-related mutations
      work and the pathogenesis of malignancies. RESULTS: Using PRISM (a PRotein
      Interactions by Structural Matching tool), we constructed the structural network
      of IL-10, which includes its first and second degree protein neighbor
      interactions. We predicted the structures of complexes involved in these
      interactions, thereby enriching the available structural data. In order to reveal
      the significance of the interactions, we exploited mutations identified in cancer
      patients, mapping them onto key proteins of this network. We analyzed the effect
      of these mutations on the interactions, and demonstrated a relation between these
      and inflammation and cancer. Our results suggest that mutations that disrupt the
      interactions of IL-10 with its receptors (IL-10RA and IL-10RB) and alpha2
      macroglobulin (A2M) may enhance inflammation and modulate anti-tumor immunity.
      Likewise, mutations that weaken the A2M-APP (amyloid precursor protein)
      association may increase the proliferative effect of APP through preventing beta
      amyloid degradation by the A2M receptor, and mutations that abolish the A2M
      Kallikrein-13 (KLK13) interaction may lead to cell proliferation and metastasis
      through the destructive effect of KLK13 on the extracellular matrix. CONCLUSIONS:
      Prediction of protein-protein interactions through structural matching can enrich
      the available cellular pathways. In addition, the structural data of protein
      complexes suggest how oncogenic mutations influence the interactions and explain
      their potential impact on IL-10 signaling in cancer and inflammation.

PMID- 25056664
TI  - Swallowing and breathing patterns during sleep in patients with obstructive sleep
      apnea.
AB  - PURPOSE: The aims of this study were to determine the frequencies of swallowing
      and swallowing associated with arousals during sleep in patients with obstructive
      sleep apnea (OSA) and to determine whether these were associated with the
      severity of OSA and differed according to the preceding breathing route. METHODS:
      Standard audio-video polysomnography including an evaluation of swallowing
      related elevation of the thyroid cartilage and breathing route (i.e., nasal or
      oronasal) was undertaken in an academic sleep laboratory. Fifty-six patients were
      analyzed (13 non-OSA patients, 17 mild, 10 moderate, and 16 severe OSA). RESULTS:
      The frequency of swallowing per hour of sleep was significantly higher in the
      severe OSA patients when compared to mild OSA patients (mild OSA, 3.1/h and
      severe OSA, 8.4/h). This was mainly due to the significantly higher frequency of
      swallowing associated with a respiratory event-related arousal in the severe OSA
      patients when compared to non- and mild OSA patients (non-OSA, 0.6/h; mild OSA,
      1.0/h; severe OSA, 6.0/h), especially when swallowing was preceded by oronasal
      breathing (non-OSA, 0.2/h; mild OSA, 0.4/h; severe OSA, 4.2/h). CONCLUSIONS:
      Swallowing frequency during sleep can increase with increasing OSA severity in
      most OSA patients. These events are predominately associated with respiratory
      event-related arousals and are more frequent when preceded by oronasal breathing.
      The observed swallowing under high ventilatory needs may compromise the
      maintenance of the pharynx as a conduit for airflow in OSA patients.

PMID- 25056665
TI  - A basic intervention improves CPAP adherence in sleep apnoea patients: a
      controlled trial.
AB  - BACKGROUND: The treatment of choice for sleep apnoea-hypopnoea syndrome (SAHS) is
      continuous positive airway pressure (CPAP). However, CPAP effectiveness strongly
      depends on patient adherence to treatment. The aim of this study was to determine
      the effectiveness of a low-cost, basic intervention on improving CPAP adherence.
      METHODS: A controlled parallel-group trial. Participants were SAHS patients for
      whom CPAP treatment was indicated. Those in the intervention group were shown the
      results of their sleep test and were told the importance of treatment adherence;
      the control group received neither. Outcomes for both groups were compared at 6
      months. The primary outcome assessed was CPAP usage. RESULTS: One hundred fifty
      four patients were included in the intervention group and 167 in the control
      group. At 6 months, the intervention group had 10% more participants with CPAP
      usage >=4 h, significantly higher adherence as compared to controls (5 +/- 1.8 h
      vs 4.3 +/- 1.7, p = 0.031), mean: 0.7 h/day and fewer discontinuations of CPAP. A
      multiple linear regression model showed that intervention group and daytime
      sleepiness were variables independently associated with treatment adherence.
      CONCLUSIONS: An inexpensive basic intervention involving communication of sleep
      test results and the importance of CPAP adherence improves adherence to CPAP
      therapy. In addition, greater daytime sleepiness is associated with higher CPAP
      adherence.

PMID- 25056666
TI  - Decreased levels of serum nesfatin-1 in patients with obstructive sleep apnea
      syndrome.
AB  - PURPOSE: Recent evidences suggest that inflammation is involved in the mechanism
      of obstructive sleep apnea syndrome (OSAS). Nesfatin-1, recently identified as
      the satiety regulator, is implicated to possess an anti-inflammatory effect. The
      aim of our study is to investigate whether serum levels of nesfatin-1 are
      associated with the presence and severity of OSAS. METHODS: A total of 196
      patients with OSAS and 104 healthy subjects were enrolled in this study. Serum
      levels of nesfatin-1 were measured by enzyme-linked immunosorbent assay. RESULTS:
      OSAS patients showed significantly reduced levels of serum nesfatin-1 levels than
      healthy controls. Multivariable logistic regression analysis indicates that serum
      nesfatin-1 levels were inversely associated with the presence of OSAS (odds
      ration (OR) 0.003, 95% confidence interval (CI) 0.001 to 0.017; P < 0.001). Serum
      levels of nesfatin-1 were significantly decreased in severe OSAS patients
      compared with mild and moderate OSAS patients. Spearman correlation analysis
      showed that serum nesfatin-1 levels were inversely correlated with the severity
      of OSAS. In addition, Spearman correlation analysis showed that serum nesfatin-1
      levels were negatively correlated with body mass index (BMI) (r = -0.299, P <
      0.001), waist-hip ratio (WHR) (r = -0.277, P < 0.001), homeostasis model
      assessment of insulin resistance (HOMA-IR) (r = -0.338, P < 0.001), and apnea
      hypopnea index (AHI) (r = -0.248, P < 0.001) in patients with OSAS. CONCLUSIONS:
      Decreased serum nesfatin-1 levels are associated with the presence and severity
      of OSAS.

PMID- 25056667
TI  - Concerns about schizophrenia or possession?

PMID- 25056668
TI  - Orthographic learning in dyslexic Spanish children.
AB  - Reading fluency is one of the basic processes of learning to read. Children begin
      to develop fluency when they are able to form orthographic representations of
      words, which provide direct, smooth, and fast reading. Dyslexic children of
      transparent orthographic systems are mainly characterized by poor reading fluency
      (Cuetos & Suarez-Coalla 2009; Spinelli, De Luca, Di Filippo, Mancini, Martelli, &
      Zoccolotti, 2005; Wimmer, 1993). Therefore, the main problem for these children
      could be the difficulty in developing orthographic representations of the words
      they read. The aim of this study was to test the ability of dyslexic Spanish
      speaking children (whose native language is Spanish) to develop orthographic
      representations and determine if the context helps them. For this, two
      experiments were conducted with a group of 100 children, 7-12 years of age. The
      groups were comprised of 20 dyslexics, 40 chronological age-matched controls and
      40 reading level-matched controls. In the first experiment, eight unfamiliar
      words (four short and four long) were presented six times within the context of a
      story. In the second experiment, eight pseudowords were presented on a computer
      and the children had to read them aloud. In both experiments, the reading and
      articulation times of experimental and control stimuli were compared, before and
      after the training. Children without dyslexia showed a decrease of the influence
      of length of word on reading speed, indicating a lexical reading, while for
      dyslexic children, the influence of length remained unchanged. These results
      appeared when the stimuli were presented in the context of a story as well as
      when presented in isolation. In short, our results describe that dyslexic
      children of transparent orthographic systems have problems in developing
      orthographic representations of words. 

PMID- 25056669
TI  - The influence of tamoxifen on normal mouse mammary gland homeostasis.
AB  - INTRODUCTION: Lineage tracing using inducible genetic labeling has emerged to be
      a powerful method for interrogating the developmental fate of cells in intact
      tissues. A common induction mechanism is the use of tamoxifen-dependent Cre
      recombinase (CreER and CreERT2), but the effects of tamoxifen at doses normally
      used in lineage-tracing studies on normal adult mammary gland homeostasis are not
      known. METHODS: We used flow cytometry and immunostaining of intact glands to
      determine whether varying doses of tamoxifen skew the distribution and the
      apoptosis and proliferation status of different types of mammary epithelial cells
      in vivo. We also examined how tamoxifen influences the number of progenitor and
      mammary repopulating units (MRUs). RESULTS: Our results indicate that >=5 mg/25 g
      body weight of tamoxifen induces a transient increase in cell proliferation and
      in the number of basal cells in the adult mammary epithelium up to 7 days after
      tamoxifen administration. However, in the medium term (3 weeks), all doses of
      tamoxifen>=1 mg/25 g body weight result in a decrease in the number of basal and
      EpCAM+CD49b- luminal cells and a decrease in progenitor cell function. Tamoxifen
      at doses>=5 mg/25 g body weight induced a transient increase in caspase-3
      mediated apoptotic cell death within the mammary epithelium. However, mammary
      epithelial cell numbers in all subpopulations were restored to their original
      levels by 8 weeks. No long-lasting effects of tamoxifen on MRU numbers or on
      pubertal ductal development were observed. CONCLUSION: Tamoxifen can skew the
      distribution of mammary cell types in a dose-dependent manner, and thus caution
      must be taken when interpreting lineage-tracing studies using high doses of
      tamoxifen, particularly when short-duration analyses of a quantitative nature are
      being performed.

PMID- 25056670
TI  - Impact of streambed morphology on the abundance and activity of ammonia-oxidizing
      bacteria.
AB  - Ammonia oxidizers catalyze the first step of nitrification. Combined microbial
      nitrification-denitrification activities are essential for the removal of excess
      nitrogen from water bodies. In sandy streambeds, bed form structures are created
      by water flow and lead to the creation of heterogeneous microenvironments. The
      objective of this study, therefore, was to investigate the effect of bed form
      morphology on the abundance and activity of ammonia-oxidizing bacteria (AOB)
      within a benthic biofilm. An 8-month-old benthic biofilm was established in a
      recirculating laboratory flume under controlled flow conditions and frequent
      amendment with ammonium. The sand bed was arranged into bed form structures. The
      highest concentrations of chlorophyll a (indicative of algae) were measured on
      the upstream side of the bed forms. The biofilm was dominated by Nitrosospira
      species, and amoA gene abundance was higher on the downstream sides of the bed
      forms with no significant difference in oxygen consumption between the upstream
      and downstream sections of the bed form. In contrast, potential ammonium
      oxidation rates were higher on the upstream sides of the bed forms. The results
      suggest that bed form morphology can affect the spatial distribution and activity
      of AOB, possibly through the creation of distinct microhabitats. These results
      contribute to our understanding of nitrogen transformations and removal from
      streams. 

PMID- 25056672
TI  - Challenge for hypertension prevention and control worldwide: the time for action.

PMID- 25056671
TI  - Semi-quantification of pneumothorax volume by lung ultrasound.
AB  - BACKGROUND: Lung ultrasound (LUS) may accurately diagnose pneumothorax. However,
      there is uncertainty about its usefulness in the quantification of pneumothorax
      size. To determine the ability of LUS in the semi-quantification of pneumothorax
      volume, we compared the projection of the lung point (LP) with the pneumothorax
      volume measured by computerized tomography (CT) and the interpleural distance on
      chest radiography (CXR). METHODS: We performed LUS in patients with pneumothorax
      and all the LP located on the chest wall were compared to CXR and CT studies. The
      primary outcome of the study was the ability of LP to grade pneumothorax volumes
      measured by CT. The secondary outcome was the accuracy of LP to predict small and
      large pneumothorax according to the societal guidelines based on CXR reading.
      RESULTS: A total of 124 patients with pneumothorax were enrolled (76 spontaneous,
      20 traumatic and 28 post-procedural). Ninety-four CXR and 58 CT were available
      for the analysis. An LP posterior to the mid axillary line corresponded to three
      different CXR criteria for large pneumothorax with sensitivity from 81.4 to 88.2
      % and specificity from 64.7 to 72.6 %. The mid axillary line also represented the
      limit for predicting greater than 15 % of lung collapse when volume is measured
      at CT, with sensitivity 83.3 % and specificity 82.4 %. CONCLUSIONS: LUS-targeted
      assessment of LP was a useful predictor of pneumothorax volume in this research
      study setting. LUS reliably classified pneumothorax size when compared to
      criteria based on CXR reading, particularly the small sized pneumothorax.
      However, LUS greatly outperformed conventional CXR reading for a graded
      quantification of the percentage of lung collapse.

PMID- 25056673
TI  - Akabane virus utilizes alternative endocytic pathways to entry into mammalian
      cell lines.
AB  - The entry mechanisms of Akabane virus (AKAV), Bunyaviridae family, have not yet
      been determined. In this study, chemical inhibitors were used to analyze
      endocytic mechanisms during AKAV infection of mammalian cell lines. The analyses
      using drug treatments followed by quantitative measurement of viral RNA and N
      protein revealed that AKAV enters non-bovine-derived cell lines (Vero, HmLu-1 and
      BHK cells) in a manner indicative of clathrin endocytosis. By contrast, AKAV
      infection in bovine-derived cell lines (LB9.K and MDBK cells) is independent of
      this pathway. Further analyses indicated that AKAV entry into bovine cell lines
      involves a non-clathrin, non-caveolae endocytic pathway that is dependent on
      dynamin. We conclude that although both cell types require a low pH for AKAV
      penetration, AKAV utilizes alternative entry pathways into mammalian cell lines. 

PMID- 25056674
TI  - First finding of Southeast Asia topotype of foot-and-mouth disease virus in
      Kinmen, Taiwan, in the 2012 outbreak.
AB  - Foot-and-mouth disease virus, a member of genus Aphthovirus within the family
      Picornaviridae, affects cloven-hoofed animals, causing foot-and-mouth disease
      characterized by vesicle development. The Southeast Asia topotype, one of the
      topotypes within serotype O of the virus, is prevalent in some Asian countries,
      but had not previously been found in Taiwan. The topotype was first found in pigs
      in Kinmen Island, Taiwan, in 2012 and identified by nucleotide sequence
      comparison and phylogenetic analysis. Outbreaks were reported at 4 farms,
      resulting in the culling of 628 pigs and 1 cattle. Pigs were the only species
      infected during the outbreak. The incursion of Southeast Asia topotype into
      Taiwan implies the expansion of the topotype in East Asia. 

PMID- 25056675
TI  - Outpatient treatment for humeral fractures in five calves.
AB  - Humeral fractures were treated in 5 calves using unilateral external fixation
      with epoxy putty fixator (type I). The surgeries were performed under sedation
      and analgesia, and it involved application of ultrasound-guided brachial plexus
      block. The surgical procedures were completed in 60 to 90 min, and each calf was
      returned to the farm on the same day. The fixation allowed each calf to remain
      with the dam and suckle without strict stall rest and was removed 11 to 62 days
      post-surgery. The clinical sign of diminished radial nerve function disappeared
      40 days to 4 months post-surgery. These observations suggest that this repair
      technique represents a feasible outpatient treatment for humeral fractures in
      calves. 

PMID- 25056676
TI  - Genetic diversity of maternal lineage in the endangered Kiso horse based on
      polymorphism of the mitochondrial DNA D-loop region.
AB  - To determine genetic characteristics of the maternal lineage of the Kiso horse
      based on polymorphisms of the mitochondrial DNA D-loop region, we collected blood
      samples from 136 Kiso horses, 91% of the entire population, and sequenced 411 bp
      from 15,437 to 15,847 in the region. First of all, we estimated the demographic
      history; by searching homology between the obtained and known sequences using
      Basic Local Alignment Search Tool, by mismatch analysis to evaluate the mutation
      processes using Arlequin, and by building a phylogenetic tree showing the
      relationship of the mtDNA haplotypes for 24 horse breeds around the world using
      Molecular Evolutionary Genetics Analysis softwear. The results suggested that
      various horses that came to Japan stayed at Kiso region and became ancestors of
      Kiso horse and also genetically supported the theory that the Kiso horse was
      historically improved by other Japanese native horse breeds. Next, we analyzed
      the diversity of current maternal lineage by classifying the resulting sequences,
      and by calculating the haplotype diversity and nucleotide diversity using
      Arlequin. Then, we visualized the relationship among haplotypes by a median
      joining network using NETWORK 4.6.0.0. The results suggested the diversity of
      maternal lineage in the Kiso horse was reasonably maintained. Lastly, we
      predicted future change of the diversity of maternal lineage in Kiso horse by
      assessing the regional distribution of the acquired haplotypes. The distribution
      suggested that diversity of maternal lineage would possibly be reducing. 

PMID- 25056677
TI  - Acute Escherichia coli mastitis in dairy cattle: diagnostic parameters associated
      with poor prognosis.
AB  - This study aimed to identify the diagnostic characteristics associated with poor
      prognosis and mortality in dairy cows with acute clinical Escherichia coli
      mastitis. On 17 dairy farms, 24 dairy cows with acute E. coli mastitis that had
      received therapeutic treatment were categorized into 2 groups by outcome: 17 cows
      that recovered (survivors) and 7 cows that died or were euthanized (non
      survivors). Two days after onset of acute E. coli mastitis, dysstasia was
      observed in non-survivors, but not in survivors. Compared with survivors,
      significantly increased hematocrit (HCT) values and non-esterified fatty acid
      (NEFA) concentrations, and significantly decreased antithrombin activity and
      platelet counts were found in non-survivors on days 2 and 3 after therapy.
      Dysstasia, associated with decreased antithrombin activity and platelet counts,
      and with increased HCT and NEFA concentrations, was considered to be the major
      prognostic indicator associated with high mortality after therapeutic treatment
      in acute E. coli mastitis. 

PMID- 25056678
TI  - Genomic reassortants of pandemic A (H1N1) 2009 virus and endemic porcine H1 and
      H3 viruses in swine in Japan.
AB  - From 2010 to 2013 in Japan, we isolated 11 swine influenza viruses (SIVs) from
      pigs showing respiratory symptoms. Sequence and phylogenetic analyses showed that
      6 H1N1 viruses originated from the pandemic (H1N1) 2009 (pdm 09) virus and the
      other 5 viruses were reassortants between SIVs and pdm 09 viruses, representing 4
      genotypes. Two H1N2 viruses contained H1 and N2 genes originated from Japanese
      H1N2 SIV together with internal genes of pdm 09 viruses. Additionally, 1 H1N2
      virus contained a further NP gene originating from Japanese H1N2 SIV. One H1N1
      virus contained only the H1 gene originating from Japanese H1 SIV in a pdm 09
      virus background. One H3N2 virus contained H3 and N2 genes originating from
      Japanese H3N2 SIV together with internal genes of pdm 09 virus. The results
      indicate that pdm 09 viruses are distributed widely in the Japanese swine
      population and that several reassortments with Japanese SIVs have occurred. 

PMID- 25056680
TI  - Characterization of Oryzias latipes glucocorticoid receptors and their unique
      response to progestins.
AB  - Various receptor bioassays, including estrogens, androgens and thyroid hormones,
      have been developed and applied successfully for assessing hormone function in a
      wide range of animal species, including fish. In fish, corticosteroids play a
      pivotal role in physiology as they do in mammals, but far less is known about the
      corticosteroid receptor system in fish compared with in mammals. Here we
      established a transient transactivation assay using the Japanese medaka, Oryzias
      latipes, glucocorticoid receptors (olGRs) and mineralocorticoid receptor to
      analyse their functional properties in a fish. We found that olGR2 was highly
      responsive to glucocorticoids, similar to the human GR, whereas the olGR1 subtype
      was minimally responsive. Thus, olGR2 most likely mediates glucocorticoid
      signaling in medaka. We further tested crosstalk between GRs and other steroid
      hormones, and found that progestins could activate or inactivate olGR2-mediating
      transcription, depending on the presence or absence of cortisol. The
      transactivation assays developed for medaka GRs provide tools to gain useful
      insights into corticosteroid signaling in fish and for in vitro screening of
      environmental substances activating GRs.

PMID- 25056681
TI  - Arterial stiffness estimation in healthy subjects: a validation of oscillometric
      (Arteriograph) and tonometric (SphygmoCor) techniques.
AB  - Arterial stiffness is an important cardiovascular risk marker, which can be
      measured noninvasively with different techniques. To validate such techniques in
      healthy subjects, we compared the recently introduced oscillometric Arteriograph
      (AG) technique with the tonometric SphygmoCor (SC) method and their associations
      with carotid ultrasound measures and traditional risk indicators. Sixty-three
      healthy subjects aged 20-69 (mean 48 +/- 15) years were included. We measured
      aortic pulse wave velocity (PWVao) and augmentation index (AIx) by AG and SC, and
      with SC also the PWVao standardized to 80% of the direct distance between carotid
      and femoral sites (St-PWVaoSC). The carotid strain, stiffness index and intima
      media thickness (cIMTmean) were evaluated by ultrasound. PWVaoAG (8.00 +/- 2.16 m
      s(-1)) was higher (P<0.001) than PWVaoSC (6.87 +/- 1.47 m s(-1)), but did not
      differ from St-PWVaoSC (7.68 +/- 1.58 m s(-1)), and correlated (P<0.001) with
      both (r = 0.54 and 0.59). St-PWVaoSC was significantly (P < 0.01) higher than
      PWVaoAG for values below median (7.4 m s(-1)). PWVao by SC and AG differed
      significantly in females (P<0.001), but not in males (P=0.40). AIxaoAG (27.5 +/-
      14.5%) was higher (P < 0.001) than AIxaoSC (20.5 +/- 17.4%), but related closely
      (r=0.97, P<0.001). St-PWVaoSC, PWVao and AIxao by SC, and PWVao and AIxao by AG
      were all related to serum cholesterol and to cIMTmean (P<0.001). Arterial
      stiffness indices by AG and SC correlate with vascular risk markers in healthy
      subjects. AIxao results by AG and SC are closely interrelated, but higher values
      are obtained by AG. In the lower range, PWVao values by AG and SC are similar,
      but differ for higher values. Our results imply the necessity to apply one and
      the same technique for repeated studies.

PMID- 25056682
TI  - Ankle-brachial blood pressure index predicts cardiovascular events and mortality
      in Japanese patients with chronic kidney disease not on dialysis.
AB  - The ankle-brachial blood pressure index (ABPI) has been recognized to have a
      predictive value for cardiovascular (CV) events and mortality in general or
      dialysis populations. However, the associations between ABPI and those outcomes
      have not been fully investigated in predialysis patients. The present study aimed
      to clarify the relationships between ABPI and both CV events and mortality in
      Japanese chronic kidney disease (CKD) patients not on dialysis. In this
      prospective observational study, we enrolled 320 patients with CKD stages 3-5 who
      were not on dialysis. At baseline, ABPI was examined and a low ABPI was defined
      as <0.9. CV events and all-cause deaths were examined in each patient. A Cox
      proportional hazards model was applied to determine the risk factors for CV
      events, as well as for mortality from CV and all causes. The median follow-up
      period was 30 months. CV events occurred in 56 patients and all-cause deaths
      occurred in 48, including 20 CV deaths. Multivariate analysis showed that age and
      low ABPI were risk factors for CV events. It was demonstrated that age, a history
      of cerebrovascular disease and low ABPI were determined as independent risk
      factors for CV mortality. In addition, age, body mass index and low ABPI were
      independently associated with all-cause mortality. In patients with CKD, low ABPI
      during the predialysis period is independently associated with poor survival and
      CV events, suggesting the usefulness of measuring ABPI for predicting CV events
      and patient survival in CKD. 

PMID- 25056683
TI  - Monitoring morphology and hydrogen coverage of nanometric Pt/gamma-Al2 O3
      particles by in situ HERFD-XANES and quantum simulations.
AB  - Platinum nanoclusters highly dispersed on gamma-alumina are widely used as
      heterogeneous catalysts. To understand the chemical interplay between the Pt
      nanoparticles, the support, and the reductive atmosphere, we performed X-ray
      absorption near edge structure (XANES) in situ experiments recorded in high
      energy resolution fluorescence detection (HERFD) mode. Spectra are assigned by
      comparison with simulated XANES spectra on models obtained by molecular dynamics
      (DFT-MD). We propose platinum cluster morphologies and quantify the hydrogen
      coverages compatible with XANES spectra recorded at variable hydrogen pressures
      and temperatures. Using cutting-edge methodologies to assign XANES spectra, this
      work gives unequalled atomic insights into the characterization of supported
      nanoclusters. 

PMID- 25056684
TI  - Conceptualizations of sleep in stress theory: exciting new directions.

PMID- 25056685
TI  - Metal-substituted zeolitic imidazolate framework ZIF-108: gas-sorption and
      membrane-separation properties.
AB  - A series of dual-metal zeolitic imidazolate framework (ZIF) crystals with SOD and
      RHO topologies was synthesised by metal substitution from ZIF-108 (Zn(2
      nitroimidazolate)2 , SOD topology) as the parent material. This was based on the
      concept that metal substitution of ZIF-108 requires a much lower activation
      energy than homogenous nucleation owing to the metastability of ZIF-108. In-depth
      investigations of the formation processes of the daughter ZIFs indicated that the
      transformation of ZIF-108 is a dissolution/heterogeneous nucleation process.
      Typical isostructural Co(2+) substitution mainly occurs at the outer surface of
      ZIF-108 and results in a core-shell structure. On the contrary, the Cu(2+) 
      substituted ZIF has a RHO topology with a homogeneous distribution of Cu(2+) ions
      in the structure. Substitution with Ni(2+) resulted in a remarkable enhancement
      in adsorption selectivity toward CO(2) over N(2) by a factor of up to 227. With
      Co(2+) -substituted nanoparticles as inorganic filler, a mixed matrix membrane
      based on polysulfone displayed greatly improved performance in the separation of
      H(2)/CH(4), CO(2)/N(2) and CO(2)/CH(4).

PMID- 25056686
TI  - Modified assertive community treatment: effectiveness on hospitalization and
      length of stay.
AB  - The objective is to assess the efficacy of a modified Assertive Community
      treatment (ACT). This is a retrospective cross-sectional study with a comparative
      group. The study group was patients with schizophrenia who had completed modified
      ACT, while the control group was those who did not receive modified ACT. The
      final sample comprises 44 patients in each group. There was no significant
      difference between both groups in number of admissions and average length of
      stay. However, in the modified ACT group there was a significant reduction in the
      number of admissions after the intervention. In conclusion readmission rate was
      significantly reduced following modified ACT intervention. 

PMID- 25056687
TI  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) and tumor necrosis factor-alpha
      (TNF-alpha) and their relation to premature atherosclerosis in beta-thalassemia
      children.
AB  - BACKGROUND/OBJECTIVES: Beta (beta)-thalassemia adults are prone to premature
      atherosclerosis but data about this complication among thalassemia children are
      few. Lipoprotein-associated phospholipase A2 (Lp-PLA2) and tumor necrosis factor
      alpha (TNF-alpha) are inflammatory markers that could be implicated in
      atherosclerotic process. We investigated Lp-PLA2 and TNF-alpha levels in beta
      thalassemia children and their relation to subclinical atherosclerosis. METHODS:
      Twenty-two beta-thalassemia major (TM), 20 beta-thalassemia intermedia children,
      and 30 age- and sex-matched healthy controls were included. Lipid profile (by
      colorimetric assay), serum ferritin, TNF-alpha, and plasma Lp-PLA2 levels (by
      enzyme-linked immunosorbent assay technique) were estimated. Carotid intima-media
      thickness (cIMT) was measured by high-resolution ultrasound. RESULTS: Both
      patient groups exhibited anti-atherogenic lipid profile except increased serum
      triglycerides. They had significantly higher plasma Lp-PLA2 and serum TNF-alpha
      compared to the controls (P < 0.001). Elevated cIMT was documented in 57% of the
      thalassemia children and was higher among hepatitis C (HCV) positive patients.
      Serum ferritin, TNF-alpha, and plasma Lp-PLA2 levels were significantly higher in
      patients with premature atherosclerosis. cIMT correlated significantly with serum
      ferritin, TNF-alpha, and plasma Lp-PLA2 in both patient groups. Among TM
      children, serum ferritin had significant positive correlation with serum TNF
      alpha and plasma Lp-PLA2. The elevation of both markers was not related to HCV
      infection. CONCLUSIONS: Premature atherosclerosis is common among young
      thalassemia children. Lp-PLA2 and TNF-alpha are significantly increased in
      thalassemia children and show strong correlations with cIMT, suggesting that both
      of them may be appreciated as modulating factors in carotid atherosclerosis
      pathophysiological process among these children.

PMID- 25056688
TI  - Does learning to read improve intelligence? A longitudinal multivariate analysis
      in identical twins from age 7 to 16.
AB  - Evidence from twin studies points to substantial environmental influences on
      intelligence, but the specifics of this influence are unclear. This study
      examined one developmental process that potentially causes intelligence
      differences: learning to read. In 1,890 twin pairs tested at 7, 9, 10, 12, and 16
      years, a cross-lagged monozygotic-differences design was used to test for
      associations of earlier within-pair reading ability differences with subsequent
      intelligence differences. The results showed several such associations, which
      were not explained by differences in reading exposure and were not restricted to
      verbal cognitive domains. The study highlights the potentially important
      influence of reading ability, driven by the nonshared environment, on
      intellectual development and raises theoretical questions about the mechanism of
      this influence.

PMID- 25056689
TI  - HIV disclosure to sexual partner and associated factors among women attending ART
      clinic at Mekelle hospital, Northern Ethiopia.
AB  - BACKGROUND: Disclosure of HIV positive status has two sets of contrary effects.
      It may motivate partner for Voluntary Counseling and Testing; on the other hand,
      it may cause blame, discrimination, depression and loss of economic support.
      Consequently, HIV positive status disclosure among women has become one of the
      major concerns that should be addressed in HIV prevention and control activities.
      This study aimed at assessing the magnitude and factors related to HIV positive
      status disclosure to sexual partners among HIV positive women. METHODS: A cross
      sectional study was conducted in Mekelle hospital from July 10-26, 2013 to
      collect data from 315 HIV positive women using a systematic random sampling.
      Descriptive and multiple logistic regression analyses were performed using SPSS
      20 for windows to estimate indicators and effect sizes of the predictors on HIV
      disclosure status to partners. RESULTS: The proportion of HIV disclosure status
      to their partner was 63.8%. Women who knew the HIV status of their sexual partner
      and those who got pretest counseling had a positive association with HIV
      disclosure with AOR of 16.9 (95% CI: 8.11, 35.21) and AOR of 2.8 (95% CI: 1.83,
      4.28). Mothers with two years or beyond, since they knew their HIV status had
      more odds (AOR = 3. 2, 95% CI: 1.7, 6.29) to disclose their HIV status to their
      partner. Mothers who had seen people with HIV positive who disclose their HIV
      status to the community (AOR = 2.1, 95% CI: 1.08, 4.01) and those who had a
      discussion prior to HIV testing (AOR = 4.87, 95% CI: 2.45, 9.71) were more likely
      to disclose their HIV status than their counterparts. CONCLUSIONS: The rate of
      HIV disclosure to their partner was low. Knowledge of HIV status of partner,
      receiving pretest counseling, longer time since the HIV testing, know people who
      disclose their status to the community and having discussion prior to HIV testing
      could influence disclosure of HIV status of mothers to their partners.

PMID- 25056690
TI  - Insufficient intake of L-histidine reduces brain histamine and causes anxiety
      like behaviors in male mice.
AB  - L-histidine is one of the essential amino acids for humans, and it plays a
      critical role as a component of proteins. L-histidine is also important as a
      precursor of histamine. Brain histamine is synthesized from L-histidine in the
      presence of histidine decarboxylase, which is expressed in histamine neurons. In
      the present study, we aimed to elucidate the importance of dietary L-histidine as
      a precursor of brain histamine and the histaminergic nervous system. C57BL/6J
      male mice at 8 wk of age were assigned to 2 different diets for at least 2 wk:
      the control (Con) diet (5.08 g L-histidine/kg diet) or the low L-histidine diet
      (LHD) (1.28 g L-histidine/kg diet). We measured the histamine concentration in
      the brain areas of Con diet-fed mice (Con group) and LHD-fed mice (LHD group).
      The histamine concentration was significantly lower in the LHD group [Con group
      vs. LHD group: histamine in cortex (means +/- SEs): 13.9 +/- 1.25 vs. 9.36 +/-
      0.549 ng/g tissue; P = 0.002]. Our in vivo microdialysis assays revealed that
      histamine release stimulated by high K(+) from the hypothalamus in the LHD group
      was 60% of that in the Con group (P = 0.012). However, the concentrations of
      other monoamines and their metabolites were not changed by the LHD. The open
      field tests showed that the LHD group spent a shorter amount of time in the
      central zone (87.6 +/- 14.1 vs. 50.0 +/- 6.03 s/10 min; P = 0.019), and the
      light/dark box tests demonstrated that the LHD group spent a shorter amount of
      time in the light box (198 +/- 8.19 vs. 162 +/- 14.1 s/10 min; P = 0.048),
      suggesting that the LHD induced anxiety-like behaviors. However, locomotor
      activity, memory functions, and social interaction did not differ between the 2
      groups. The results of the present study demonstrated that insufficient intake of
      histidine reduced the brain histamine content, leading to anxiety-like behaviors
      in the mice.

PMID- 25056691
TI  - Skeletal muscle Ras-related GTP binding B mRNA and protein expression is
      increased after essential amino acid ingestion in healthy humans.
AB  - Essential amino acids (EAAs) are potent stimulators of mechanistic target of
      rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis. However,
      regulators upstream of mTORC1 that are responsive to EAA availability are not
      well described, especially in human skeletal muscle. The purpose of this study
      was to determine changes in leucyl-tRNA synthetase (LARS/LARS) and Ras-related
      GTP binding B (RAGB/RAGB) mRNA and protein expression in healthy human skeletal
      muscle after acute EAA ingestion. Muscle biopsies sampled from the vastus
      lateralis were obtained from 13 young adults (7 males, 6 females; aged 22.9 +/-
      0.9 y; body mass index 21.7 +/- 0.9 kg/m(2)) in the fasting state (baseline) and
      1 and 3 h after EAA (13 g; 2.4 g of Leu) ingestion. Real-time quantitative
      polymerase chain reaction and Western blotting were used to determine changes in
      LARS/LARS and RAGB/RAGB mRNA and protein expression, respectively. Stable isotope
      tracers and gas chromatography mass spectrometry were used to determine Leu
      intracellular concentrations and muscle protein synthesis. EAA ingestion
      increased RAGB/RAGB mRNA (~60%) and protein (~100%) abundance in adult skeletal
      muscle (P <= 0.05). EAAs also increased muscle Leu concentrations (~130%), mTOR
      phosphorylation (~30%), and muscle protein synthesis (~50%; P <= 0.05) but did
      not alter muscle LARS/LARS abundance (P > 0.05). We conclude that acute EAA
      ingestion is capable of increasing RAGB expression in human skeletal muscle.
      Future work is needed to determine whether this adaptive response is important to
      promote muscle protein anabolism in humans. This trial was registered at
      clinicaltrials.gov as NCT01669590.

PMID- 25056692
TI  - Dietary bovine lactoferrin increases intestinal cell proliferation in neonatal
      piglets.
AB  - Lactoferrin is a bioactive milk protein that stimulates cell proliferation in
      vitro; however, limited in vivo evidence exists to allow lactoferrin to be
      incorporated into infant formula. Herein, the effect of dietary bovine
      lactoferrin (bLF) on neonatal intestinal growth and maturation was investigated
      guided by the hypothesis that bLF would increase cellular proliferation leading
      to functional differences in neonatal piglets. Colostrum-deprived piglets were
      fed formula containing 0.4 [control (Ctrl)], 1.0 (LF1), or 3.6 (LF3) g bLF/L for
      the first 7 or 14 d of life. To provide passive immunity, sow serum was provided
      orally during the first 36 h of life. Intestinal cell proliferation,
      histomorphology, mucosal DNA concentration, enzyme activity, gene expression, and
      fecal bLF content were measured. Intestinal enzyme activity, DNA concentration,
      and villus length were unaffected by bLF. However, crypt proliferation was 60%
      greater in LF1- and LF3-fed piglets than in Ctrl piglets, and crypt depth and
      area were 20% greater in LF3-fed piglets than in Ctrl piglets. Crypt cells from
      LF3-fed piglets had 3-fold higher beta-catenin mRNA expression than did crypt
      cells from Ctrl piglets. Last, feces of piglets fed bLF contained intact bLF,
      suggesting that some bLF was resistant to digestion and could potentially affect
      intestinal proliferation through direct interaction with intestinal epithelial
      cells. This study is the first to our knowledge to show that dietary bLF
      stimulates crypt cell proliferation in vivo. The increased beta-catenin
      expression indicates that Wnt signaling may in part mediate the stimulatory
      effect of bLF on intestinal cell proliferation. 

PMID- 25056693
TI  - Glycogen synthase kinase 3 beta in somites plays a role during the angiogenesis
      of zebrafish embryos.
AB  - Glycogen synthase kinase 3 beta (Gsk3b) acts as a negative modulator in
      endothelial cells through the Wnt/beta-catenin/PI3K/AKT/Gsk3b axis in cancer
      induced angiogenesis. However, the function of Gsk3b during embryonic
      angiogenesis remains unclear. Here, either gsk3b knockdown by morpholino or Gsk3b
      loss of activity by LiCl treatment had serious phenotypic consequences, such as
      defects in the positioning and patterning of intersegmental blood vessels and
      reduction of vegfaa121 and vegfaa165 transcripts. In embryos treated with the
      phosphatidylinositol 3-kinase inhibitor, angiogenesis was severely inhibited,
      along with reduced Wnt, phosphorylated AKT and phosphorylated Gsk3b, suggesting
      that the remaining Gsk3b in somites could still degrade beta-catenin, resulting
      in decreased vascular endothelial growth factor Aa(VegfAa) expression. However,
      in gsk3b-mRNA-overexpressed embryos, intersegmental vessels ectopically sprouted
      by the increase in phosphorylated-Gsk3b which prevented the degradation of beta
      catenin and promoted the increase in phosphorylated AKT activity, thus increasing
      VegfAa expression in somites. Interestingly, the Gsk3b-dependent cross-talk
      between PI3K/AKT and Wnt/beta-catenin suggests that Wnt/beta-catenin and PI3K/AKT
      interaction controls embryonic angiogenesis by a positive feedback loop rather
      than a hierarchical framework such as that found in cancer-induced angiogenesis.
      Thus, both active and inactive forms of Gsk3b mediate the cooperative signaling
      between Wnt/beta-catenin and PI3K/AKT to control VegfAa expression in somites
      during angiogenesis in zebrafish embryos.

PMID- 25056694
TI  - Serum concentrations of gastrin after famotidine and omeprazole administration to
      dogs.
AB  - BACKGROUND: The duration of antacid-induced hypergastrinemia after cessation of
      administration of omeprazole and famotidine apparently has not been determined in
      dogs. HYPOTHESIS: That serum gastrin will return to basal concentrations by 7
      days after cessation of famotidine or omeprazole administration. ANIMALS: Nine
      healthy, adult, male, research colony dogs. METHODS: Randomized, cross-over
      design. Serum gastrin was determined daily for 7 days to establish baseline
      concentrations. Famotidine (1.0 mg/kg q24h) or omeprazole (1.0 mg/kg q24h) was
      administered PO for 7 days followed by a 14-day washout. Serum concentrations of
      gastrin were determined daily during 7 days of administration and daily for 7
      days after cessation of administration. Each drug was evaluated in 8 of the 9
      dogs. RESULTS: Omeprazole caused a significant increase in serum gastrin
      concentration (37.2 +/- 7.3 to 71.3 +/- 19.0 ng/L; P = .006). Famotidine induced
      a transient increase in serum gastrin (37.2 +/- 7.3 to 65.5 +/- 38.5 ng/L; P =
      .02) that peaked at administration day 3 and declined thereafter. By day 7 after
      cessation of both drugs, there was no difference in serum gastrin concentrations
      compared to those before administration (famotidine P = .99; omeprazole P = .99).
      During or after administration, gastrin concentrations above 3 times the upper
      reference range were rare (12 of 224 samples). CONCLUSIONS AND CLINICAL
      IMPORTANCE: A 7-day withdrawal from short-term administration of famotidine or
      omeprazole is sufficient for serum gastrin to return to baseline concentrations.
      Withholding famotidine or omeprazole for longer before investigating pathologic
      causes of hypergastrinemia is unnecessary.

PMID- 25056695
TI  - Dual-memory processes in crack cocaine dependents: The effects of childhood
      neglect on recall.
AB  - Exposure to adversities during sensitive periods of neurodevelopment is
      associated with the subsequent development of substance dependence and exerts
      harmful, long-lasting effects upon memory functioning. In this study, we
      investigated the relationship between childhood neglect (CN) and memory using a
      dual-process model that quantifies recollective and non-recollective retrieval
      processes in crack cocaine dependents. Eighty-four female crack cocaine-dependent
      inpatients who did (N = 32) or did not (N = 52) report a history of CN received
      multiple opportunities to study and recall a short list composed of familiar and
      concrete words and then received a delayed-recall test. Crack cocaine dependents
      with a history of CN showed worse performance on free-recall tests than did
      dependents without a history of CN; this finding was associated with declines in
      recollective retrieval (direct access) rather than non-recollective retrieval. In
      addition, we found no evidence of group differences in forgetting rates between
      immediate- and delayed-recall tests. The results support developmental models of
      traumatology and suggest that neglect of crack cocaine dependents in early life
      disrupts the adult memory processes that support the retrieval of detailed
      representations of events from the past. 

PMID- 25056696
TI  - Translating the molecular hallmarks of colorectal cancer to patient therapies: an
      interview with Owen Sansom.

PMID- 25056697
TI  - Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?
AB  - Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal
      myeloid progenitor cells in the bone marrow and blood. Advances in cancer
      genomics have revealed the spectrum of somatic mutations that give rise to human
      AML and drawn our attention to its molecular evolution and clonal architecture.
      It is now evident that most AML genomes harbour small numbers of mutations, which
      are acquired in a stepwise manner. This characteristic, combined with our ability
      to identify mutations in individual leukaemic cells and our detailed
      understanding of normal human and murine haematopoiesis, makes AML an excellent
      model for understanding the principles of cancer evolution. Furthermore, a better
      understanding of how AML evolves can help us devise strategies to improve the
      therapy and prognosis of AML patients. Here, we draw from recent advances in
      genomics, clinical studies and experimental models to describe the current
      knowledge of the clonal evolution of AML and its implications for the biology and
      treatment of leukaemias and other cancers. 

PMID- 25056698
TI  - Cyclosporin A enhances neural precursor cell survival in mice through a
      calcineurin-independent pathway.
AB  - Cyclosporin A (CsA) has direct effects on neural stem and progenitor cells
      (together termed neural precursor cells; NPCs) in the adult central nervous
      system. Administration of CsA in vitro or in vivo promotes the survival of NPCs
      and expands the pools of NPCs in mice. Moreover, CsA administration is effective
      in promoting NPC activation, tissue repair and functional recovery in a mouse
      model of cortical stroke. The mechanism(s) by which CsA mediates this cell
      survival effect remains unknown. Herein, we examined both calcineurin-dependent
      and calcineurin-independent pathways through which CsA might mediate NPC
      survival. To examine calcineurin-dependent pathways, we utilized FK506
      (Tacrolimus), an immunosuppressive molecule that inhibits calcineurin, as well as
      drugs that inhibit cyclophilin A-mediated activation of calcineurin. To evaluate
      the calcineurin-independent pathway, we utilized NIM811, a non-immunosuppressive
      CsA analog that functions independently of calcineurin by blocking mitochondrial
      permeability transition pore formation. We found that only NIM811 can entirely
      account for the pro-survival effects of CsA on NPCs. Indeed, blocking signaling
      pathways downstream of calcineurin activation using nNOS mice did not inhibit CsA
      mediated cell survival, which supports the proposal that the effects are
      calcinuerin-independent. In vivo studies revealed that NIM811 administration
      mimics the pro-survival effects of CsA on NPCs and promotes functional recovery
      in a model of cortical stroke, identical to the effects seen with CsA
      administration. We conclude that CsA mediates its effect on NPC survival through
      calcineurin-independent inhibition of mitochondrial permeability transition pore
      formation and suggest that this pathway has potential therapeutic benefits for
      developing NPC-mediated cell replacement strategies. 

PMID- 25056699
TI  - Insulin-like growth factor-1 induces regulatory T cell-mediated suppression of
      allergic contact dermatitis in mice.
AB  - Allergic contact dermatitis (ACD) is triggered by an aberrant hyperinflammatory
      immune response to innocuous chemical compounds and ranks as the world's most
      prevalent occupational skin condition. Although a variety of immune effector
      cells are activated during ACD, regulatory T (Treg) cells are crucial in
      controlling the resulting inflammation. Insulin-like growth factor-1 (IGF-1)
      regulates cell proliferation and differentiation and accelerates wound healing
      and regeneration in several organs including the skin. Recently IGF-1 has also
      been implicated in protection from autoimmune inflammation by expansion of Treg
      cells. Here, we demonstrate that ectopic expression of IGF-1 in mouse skin
      suppresses ACD in a Treg cell-specific manner, increasing the number of Foxp3+
      Treg cells in the affected area and stimulating lymphocyte production of the anti
      inflammatory cytokine interleukin 10. Similar therapeutic effects can be achieved
      with systemic or topical delivery of IGF-1, implicating this growth factor as a
      promising new therapeutic option for the treatment of ACD.

PMID- 25056701
TI  - Transcription: The transcriptional effects of MYC.

PMID- 25056700
TI  - TGF-beta mediates early angiogenesis and latent fibrosis in an Emilin1-deficient
      mouse model of aortic valve disease.
AB  - Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF),
      fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein
      that regulates elastogenesis and inhibits TGF-beta signaling, but the role of
      Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1
      deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1
      and Erk2) TGF-beta dysregulation. Using histology, immunohistochemistry, electron
      microscopy, quantitative gene expression analysis, immunoblotting and
      echocardiography, we examined the effects of Emilin1 deficiency (Emilin1-/-) in
      mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell
      matrix defects in aortic valve tissue, including EFF, that progress to latent AVD
      and premature death. The Emilin1-/- aortic valve displays early aberrant
      provisional angiogenesis and late neovascularization. In addition, Emilin1-/-
      aortic valves are characterized by early valve interstitial cell activation and
      proliferation and late myofibroblast-like cell activation and fibrosis.
      Interestingly, canonical TGF-beta signaling (phosphorylated Smad2 and Smad3) is
      upregulated constitutively from birth to senescence, whereas non-canonical TGF
      beta signaling (phosphorylated Erk1 and Erk2) progressively increases over time.
      Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is
      mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-beta
      activation. The early manifestation of EFF and aberrant angiogenesis suggests
      that these processes are crucial intermediate factors involved in disease
      progression and therefore might provide new therapeutic targets for human AVD.

PMID- 25056702
TI  - Oncogenes: All eyes on YAP1.

PMID- 25056708
TI  - Cerebrospinal fluid and plasma C-reactive protein and aggression in personality
      disordered subjects: a pilot study.
AB  - C-reactive protein (CRP), in the plasma, serves as a marker of systemic
      inflammation and has been shown to correlate with history of actual aggressive
      behavior, and as a personality trait of aggressive tendency, in human subjects.
      This pilot study was conducted to determine if plasma CRP levels are correlated
      with cerebrospinal fluid levels (CSF CRP) and if CSF CRP also correlates with
      aggression. If so, this would suggest a role for central inflammatory processes
      in human aggression. Both plasma and basal lumbar CSF samples were obtained from
      17 subjects with DSM-5 personality disorder and assayed for CRP. Plasma and CSF
      CRP levels were correlated (r = 0.65, p = 0.005) and each correlated with
      aggression (Plasma: r = 0.53, p = 0.029; CSF: r = 0.84, p < 0.001). When
      considered simultaneously, CSF CRP, but not plasma CRP, uniquely correlated with
      aggression. No relationship was seen with other measures of psychopathology.
      These data suggest a positive relationship between central nervous system CRP and
      aggression in humans.

PMID- 25056709
TI  - Electrophysiological characteristics of task-specific tremor in 22
      instrumentalists.
AB  - Our aim was to address three characteristics of task-specific tremor in musicians
      (TSTM): First, we quantified muscular activity of flexor and extensor muscles, of
      coactivation as well as tremor acceleration. Second, we compared muscular
      activity between task-dependent and position-dependent tremor. Third, we
      investigated, whether there is an overflow of muscular activity to muscles
      adjacent to the affected muscles in TSTM. Tremor acceleration and muscular
      activity were measured in the affected muscles and the muscles adjacent to the
      affected muscles in 22 patients aged 51.5 +/- 11.4 years with a task-specific
      tremor. We assessed power of muscular oscillatory activity and calculated the
      coherence between EMG activity of affected muscles and tremor acceleration as
      well as between adjacent muscles and tremor acceleration. This was done for task
      dependent and position-dependent tremor. We found the highest power and coherence
      of muscular oscillatory activity in the frequency range of 3-8 Hz for affected
      and adjacent muscles. No difference was found between task-dependent and position
      dependent tremor in neither power nor coherence measures. Our results generalize
      previous results of a relation between coactivation and tremor among a variety of
      musicians. Furthermore, we found coherence of adjacent muscles and TSTM. This
      indicates that overflow exists in TSTM and suggests an association of TST with
      dystonia.

PMID- 25056707
TI  - Non-small-cell lung cancers: a heterogeneous set of diseases.
AB  - Non-small-cell lung cancers (NSCLCs), the most common lung cancers, are known to
      have diverse pathological features. During the past decade, in-depth analyses of
      lung cancer genomes and signalling pathways have further defined NSCLCs as a
      group of distinct diseases with genetic and cellular heterogeneity. Consequently,
      an impressive list of potential therapeutic targets was unveiled, drastically
      altering the clinical evaluation and treatment of patients. Many targeted
      therapies have been developed with compelling clinical proofs of concept;
      however, treatment responses are typically short-lived. Further studies of the
      tumour microenvironment have uncovered new possible avenues to control this
      deadly disease, including immunotherapy. 

PMID- 25056710
TI  - Chromosomal manipulation in Senegalese sole (Solea senegalensis Kaup, 1858):
      induction of triploidy and gynogenesis.
AB  - In this study we have developed protocols for induced triploidy and gynogenesis
      of Senegalese sole (Solea senegalensis), a promising flatfish species for marine
      aquaculture, in order to: 1) identify the sex-determination mechanism; and 2) to
      improve its production by generating a) sterile fish, avoiding problems related
      with sexual maturation, and b) all-female stocks, of higher growth rate.
      Triploidy was induced by means of a cold shock. Gynogenesis was induced by
      activating eggs with UV-irradiated sperm, and to prompt diploid gynogenesis, a
      cold-shock step was also used. Ploidy of putative triploid larvae and gynogenetic
      embryos were determined by means of karyotyping and microsatellite analysis.
      Haploid gynogenetic embryos showed the typical "haploid syndrome". As expected,
      triploid and gynogenetic groups showed lower fertilization, hatching, and
      survival rates than in the diploid control group. Survival rate, calculated 49
      days after hatching, for haploid and diploid gynogenetic groups was similar to
      those observed in other fish species (0% and 62.5%, respectively), whereas
      triploids showed worse values (45%). Sex was determined macroscopically and by
      histological procedures, revealing that all the diploid gynogenetic individuals
      were females. In conclusion, we have successfully applied chromosomal
      manipulation techniques in the flatfish species Senegalese sole in order to
      produce triploid, haploid, and diploid gynogenetic progenies.

PMID- 25056713
TI  - Aligning electronic and protonic energy levels of proton-coupled electron
      transfer in water oxidation on aqueous TiO2.
AB  - The high overpotential in water oxidation on anodes is a limiting factor for the
      large-scale application of photoelectrochemical cells. To overcome this
      limitation, it is essential to understand the four proton-coupled electron
      transfer (PCET) steps in the reaction mechanism and their implications to the
      overpotential. Herein, a simple scheme to compute the energies of the PCET steps
      in water oxidation on the aqueous TiO2 surface using a hybrid density functional
      is described. An energy level diagram for fully decoupled electron- and proton
      transfer reactions in which both electronic and protonic levels are placed on the
      same potential scale is also described. The level diagram helps to visualize the
      electronic and protonic components of the overpotential, and points out what are
      needed to improve. For TiO2, it is found that its catalytic activity is due to
      aligning the protonic energy levels in the PCET steps, while improving the
      activity requires also aligning the electronic levels.

PMID- 25056712
TI  - Optimizing Surveillance for South American Origin Influenza A Viruses Along the
      United States Gulf Coast Through Genomic Characterization of Isolates from Blue
      winged Teal (Anas discors).
AB  - Relative to research focused on inter-continental viral exchange between Eurasia
      and North America, less attention has been directed towards understanding the
      redistribution of influenza A viruses (IAVs) by wild birds between North America
      and South America. In this study, we genomically characterized 45 viruses
      isolated from blue-winged teal (Anas discors) along the Texas and Louisiana Gulf
      Coast during March of 2012 and 2013, coincident with northward migration of this
      species from Neotropical wintering areas to breeding grounds in the United States
      and Canada. No evidence of South American lineage genes was detected in IAVs
      isolated from blue-winged teal supporting restricted viral gene flow between the
      United States and southern South America. However, it is plausible that blue
      winged teal redistribute IAVs between North American breeding grounds and
      wintering areas throughout the Neotropics, including northern South America, and
      that viral gene flow is limited by geographical barriers further south (e.g., the
      Amazon Basin). Surveillance for the introduction of IAVs from Central America and
      northern South America into the United States may be further optimized through
      genomic characterization of viruses resulting from coordinated, concurrent
      sampling efforts targeting blue-winged teal and sympatric species throughout the
      Neotropics and along the United States Gulf Coast.

PMID- 25056714
TI  - Value of gadoxetate biliary transit time in determining hepatocyte function.
AB  - OBJECTIVE: To determine if transit time for excretion of gadoxetate into major
      bile ducts and duodenum correlates with clinical models of hepatocellular
      function. METHODS: This retrospective research was approved by the Institutional
      Review Board with waiver of informed consent. Search of the radiology database
      from January 1, 2013 to March 4, 2014 revealed 84 patients with chronic liver
      disease (65 males, mean age 47 years). Eighteen control subjects with no known
      liver disease or risk factors were also enrolled for analysis (9 males, mean age
      43 years). MRI was performed with hepatobiliary phases at 10, 15, 20, and 25 min
      after injection of 0.025 mmol/kg of gadoxetate (Primovist, Bayer HealthCare,
      Shanghai, China). The time of excreted contrast appearing in the biliary tree and
      in the duodenum was recorded. Linear trend analysis was performed to determine
      the relationship between excretion time and hepatic function. RESULTS: The
      patient cohort was stratified by Child-Pugh classification (A, B, and C with n =
      53, 27, and 4, respectively). Arrival of gadoxetate in the gall bladder at 10-min
      hepatobiliary phase was seen in 87% of control group and 45% of Child-Pugh A
      group (p = 0.02). There was no difference between these groups for later
      hepatobiliary phases. The arrival of biliary contrast in the right hepatic duct,
      common bile duct, and gall bladder were significantly earlier in the Child-Pugh A
      group compared to the Child-Pugh B/C group at all hepatobiliary phases after 10
      min (p < 0.05). Linear trend analysis showed that biliary transit times were
      significantly delayed with worsening liver function (p = 0.01). There was no
      difference in entry time of gadoxetate into the duodenum between the normal,
      Child-Pugh A, and Child-Pugh B/C groups. CONCLUSIONS: The transit time for
      gadoxetate to appear in extrahepatic duct is a reasonable indicator of liver
      function, and may be included in radiology reports. The appearance in the
      duodenum, however, may depend on factors other than liver function, such as the
      physiology of the gallbladder and sphincter of Oddi.

PMID- 25056715
TI  - Innate IFN-gamma promotes development of experimental autoimmune
      encephalomyelitis: a role for NK cells and M1 macrophages.
AB  - The role of IFN-gamma in the pathogenesis of autoimmune diseases is
      controversial. Although Th1 cells can induce experimental autoimmune
      encephalomyelitis (EAE), IFN-gamma can suppress Th17 cells that are pathogenic in
      EAE. Here we show that NK cells provide an early source of IFN-gamma during
      development of EAE. Depletion of NK cells or neutralization of IFN-gamma delayed
      the onset of EAE and was associated with reduced infiltration of IL-17(+) and GM
      CSF(+) T cells into the CNS. In the passive transfer model, immune cells from
      myelin oligodendrocyte glycoprotein (MOG)-immunized IFN-gamma(-/-) mice failed to
      induce EAE, despite producing IL-17 and GM-CSF. The macrophages expressed markers
      of M2 activation and the T cells had low very late antigen-4 (VLA-4) expression
      and failed to infiltrate the CNS. Addition of recombinant IFN-gamma to immune
      cells from the IFN-gamma(-/-) mice activated M1 macrophages and restored VLA-4
      expression, migratory, and encephalitogenic activity of T cells. Furthermore,
      treatment of recipient mice with anti-VLA-4 neutralizing antibody abrogated EAE
      induced by transfer of T cells from WT mice. Our findings demonstrate IFN-gamma
      producing T cells are not required for development of EAE, but NK cell-derived
      IFN-gamma has a key role in promoting M1 macrophage expansion and VLA-4-mediated
      migration of encephalitogenic T cells into the CNS. 

PMID- 25056717
TI  - The EU paediatric regulation: still a large discrepancy between therapeutic needs
      and approved paediatric investigation plans.
AB  - PURPOSE: Prior to the implementation of the EU Paediatric Regulation, the
      European Medicines Agency (EMA) defined unmet paediatric needs for active
      substances already available on the market. Seven years after the Paediatric
      Regulation came into force, we investigated the extent to which previously
      identified needs have led to programmes for generating evidence necessary for the
      regulatory approval of medicines for managing childhood conditions. METHODS: The
      websites of the EMA and the European Commission Community Research and
      Development Information Service (CORDIS) were systematically screened to identify
      active substances from the assessment of paediatric needs, off-patent priority
      list, agreed Paediatric Investigation Plans (PIP) and 7th Framework Programme
      (FP7) projects related to paediatric medicines. RESULTS: A total of 357 active
      substances with paediatric needs were identified by June 2013. 511 PIPs were
      agreed by the Paediatric Committee at the EMA (PDCO), including 51 (14.3 %) PIPs
      for a previously identified need. Amongst those, 21 were off-patent at the time
      of the PIP approval, 15 of which received funding from the European Commission's
      FP7. According to the assessment of paediatric needs, evidence is particularly
      needed for active substances treating cardiovascular diseases (n = 61), cancer (n
      = 40) and in the field of anaesthesiology (n = 38). Whereas oncology drugs (n =
      66) were frequently represented in PIPs, drugs for cardiovascular diseases (n =
      39) and anaesthesiology (n = 3) rarely were. CONCLUSIONS: Most PIPs are
      attributable to marketing authorisations of new active substances, whereas off
      patent drugs which are commonly used off-label remain unstudied to a large
      extent. More effort including ongoing research funding is essential to further
      regularise and standardise paediatric pharmacotherapy.

PMID- 25056716
TI  - Cerebral abscess due to Serratia marcescens.

PMID- 25056718
TI  - Dual field effects in electrolyte-gated spinel ferrite: electrostatic carrier
      doping and redox reactions.
AB  - Controlling the electronic properties of functional oxide materials via external
      electric fields has attracted increasing attention as a key technology for next
      generation electronics. For transition-metal oxides with metallic carrier
      densities, the electric-field effect with ionic liquid electrolytes has been
      widely used because of the enormous carrier doping capabilities. The gate-induced
      redox reactions revealed by recent investigations have, however, highlighted the
      complex nature of the electric-field effect. Here, we use the gate-induced
      conductance modulation of spinel ZnxFe3-xO4 to demonstrate the dual contributions
      of volatile and non-volatile field effects arising from electronic carrier doping
      and redox reactions. These two contributions are found to change in opposite
      senses depending on the Zn content x; virtual electronic and chemical field
      effects are observed at appropriate Zn compositions. The tuning of field-effect
      characteristics via composition engineering should be extremely useful for
      fabricating high-performance oxide field-effect devices.

PMID- 25056711
TI  - Cyclic nucleotide phosphodiesterases: important signaling modulators and
      therapeutic targets.
AB  - By catalyzing hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP), cyclic nucleotide phosphodiesterases are critical
      regulators of their intracellular concentrations and their biological effects. As
      these intracellular second messengers control many cellular homeostatic
      processes, dysregulation of their signals and signaling pathways initiate or
      modulate pathophysiological pathways related to various disease states, including
      erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure,
      intermittent claudication, chronic obstructive pulmonary disease, and psoriasis.
      Alterations in expression of PDEs and PDE-gene mutations (especially mutations in
      PDE6, PDE8B, PDE11A, and PDE4) have been implicated in various diseases and
      cancer pathologies. PDEs also play important role in formation and function of
      multimolecular signaling/regulatory complexes, called signalosomes. At specific
      intracellular locations, individual PDEs, together with pathway-specific
      signaling molecules, regulators, and effectors, are incorporated into specific
      signalosomes, where they facilitate and regulate compartmentalization of cyclic
      nucleotide signaling pathways and specific cellular functions. Currently, only a
      limited number of PDE inhibitors (PDE3, PDE4, PDE5 inhibitors) are used in
      clinical practice. Future paths to novel drug discovery include the crystal
      structure-based design approach, which has resulted in generation of more
      effective family-selective inhibitors, as well as burgeoning development of
      strategies to alter compartmentalized cyclic nucleotide signaling pathways by
      selectively targeting individual PDEs and their signalosome partners. 

PMID- 25056719
TI  - Postoperative bladder and sexual function in patients undergoing surgery for
      rectal cancer: a systematic review and meta-analysis of laparoscopic versus open
      resection of rectal cancer.
AB  - There have been conflicting opinions regarding the superiority of open and
      laparoscopic surgery in preserving bladder and sexual function after rectal
      cancer surgery. This systematic review and meta-analysis aims to pool the
      available data comparing the impact of surgical approaches on postoperative
      sexual and urinary function. A search of Pubmed, Medline, Cochrane and Embase was
      undertaken and studies from January 2000 to February 2013 were identified. We
      included, in our meta-analysis, both prospective and retrospective studies that
      compared laparoscopic surgery and open surgery for rectal cancer. A total of 876
      patients undergoing rectal cancer surgery (lap n = 468, open n = 408) were
      examined. In men, postoperative ejaculatory function and erectile dysfunction
      evaluated from two studies comprising of 74 patients showed no difference between
      groups. The rate of overall sexual dysfunction evaluated from five studies
      comprising of 289 patients revealed a rate of 34 % in both the open and lap
      groups. Postoperative urinary function evaluated from five studies comprising of
      312 patients showed no difference between groups. In women, postoperative sexual
      and urinary function were evaluated from five studies comprising of 321 patients.
      Three studies (n = 219) reported no difference in sexual function between groups.
      Postoperative urinary function evaluated from four studies comprising of 212
      patients was found to be comparable. The available data are limited, but suggest
      that neither form of surgical approach be it laparoscopy or open surgery
      demonstrate superiority in preservation of sexual and bladder function. Further
      research into the technical aspects of surgery and evaluating newer minimally
      invasive technologies such as the robot may prove to be useful in improving
      functional outcomes of rectal cancer patients.

PMID- 25056720
TI  - High burden of private mutations due to explosive human population growth and
      purifying selection.
AB  - BACKGROUND: Recent studies have shown that human populations have experienced a
      complex demographic history, including a recent epoch of rapid population growth
      that led to an excess in the proportion of rare genetic variants in humans today.
      This excess can impact the burden of private mutations for each individual,
      defined here as the proportion of heterozygous variants in each newly sequenced
      individual that are novel compared to another large sample of sequenced
      individuals. RESULTS: We calculated the burden of private mutations predicted by
      different demographic models, and compared with empirical estimates based on data
      from the NHLBI Exome Sequencing Project and data from the Neutral Regions (NR)
      dataset. We observed a significant excess in the proportion of private mutations
      in the empirical data compared with models of demographic history without a
      recent epoch of population growth. Incorporating recent growth into the model
      provides a much improved fit to empirical observations. This phenomenon becomes
      more marked for larger sample sizes, e.g. extrapolating to a scenario in which
      10,000 individuals from the same population have been sequenced with perfect
      accuracy, still about 1 in 400 heterozygous sites (or about 6,000 variants) at
      the 10,001 st individual are predicted to be novel, 18-times as predicted in the
      absence of recent population growth. The proportion of private mutations is
      additionally increased by purifying selection, which differentially affect
      mutations of different functional annotations. CONCLUSIONS: The burden of private
      mutations for each individual, which are singletons (i.e. appearing in a single
      copy) in a larger sample that includes this individual, is predicted to be
      greatly increased by recent population growth, as well as by purifying selection.
      Comparison with empirical data supports that European populations have
      experienced recent rapid population growth, consistent with previous studies.
      These results have important implications to the design and analysis of
      sequencing-based association studies of complex human disease as they pertain to
      private and very rare variants. They also imply that personalized genomics will
      indeed have to be very personal in accounting for the large number of private
      mutations.

PMID- 25056721
TI  - Partner switching can favour cooperation in a biological market.
AB  - Intraspecific cooperation and interspecific mutualisms can be promoted by
      mechanisms that reduce the frequency with which cooperative organisms are
      exploited by unhelpful partners. One such mechanism consists of changing partners
      after interacting with an uncooperative individual. I used McNamara et al.'s
      (Nature, 451, 2008, 189) partner switching model as a framework to examine
      whether this mechanism can select for increased cooperative investment by house
      sparrows (Passer domesticus) collaborating to rear offspring; previous research
      on this species has shown that substantial cooperative investments by both pair
      members are required to achieve high pay-offs from collaborating. I found that
      the poorer the outcome of a breeding attempt relative to the number of eggs the
      female invested, the greater the likelihood of partner switching. The incidence
      of partner switching changed seasonally, with peak switching coinciding with an
      increase in the number of alternative partners available to females. After
      females switched partners, their breeding outcomes rose to match those of females
      that remained with the same partner; this was not the case for males that
      switched partners. Consistent with the model's prediction, males in stable
      partnerships achieved over 25% higher than average reproductive success, which
      was attributable to both persistently good breeding outcomes and their older
      partners' high fecundity. These results provide empirical support for the
      hypothesis that partner switching favours increased cooperative investment
      levels, and they demonstrate that variation in the relative value of by-product
      benefits can enhance that process.

PMID- 25056722
TI  - High-density lipoprotein from patients with coronary heart disease loses anti
      thrombotic effects on endothelial cells: impact on arterial thrombus formation.
AB  - Thrombus formation is determined by the balance between pro- thrombotic mediators
      and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects
      exerts anti-thrombotic properties. Whether this is also the case for HDL from
      patients with stable coronary heart disease (CHD) or acute coronary syndrome
      (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 ug/ml) from
      healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression
      and activity, while HDL (50 ug/ml) from CHD and ACS patients did not. Similarly,
      only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI)
      expression and tissue plasminogen activator (tPA) release, while HDL from CHD and
      ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen
      activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients
      enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation
      with L-NAME (100 umol/l) abolished the anti-thrombotic effects of healthy HDL on
      TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked
      the effects of healthy HDL and counterbalanced the loss of anti-thrombotic
      effects of HDL from CHD and ACS patients in endothelial cells. In line with this
      observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased
      endothelial NO production. In the laser-injured carotid artery of the mouse,
      thrombus formation was delayed in animals treated with healthy HDL compared with
      mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion,
      HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and
      to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus
      formation.

PMID- 25056725
TI  - Endogenous ROS levels in C. elegans under exogenous stress support revision of
      oxidative stress theory of life-history tradeoffs.
AB  - BACKGROUND: The oxidative stress theory of life-history tradeoffs states that
      oxidative stress caused by damaging free radicals directly underpins tradeoffs
      between reproduction and longevity by altering the allocation of energetic
      resources between these tasks. We test this theory by characterizing the effects
      of exogenous oxidative insult and its interaction with thermal stress and diet
      quality on a suite of life-history traits and correlations in Caenorhabditis
      elegans nematodes. We also quantify demographic aging rates and endogenous
      reactive oxygen species (ROS) levels in live animals. RESULTS: Our findings
      indicate a tradeoff between investment in reproduction and antioxidant defense
      (somatic maintenance) consistent with theoretical predictions, but correlations
      between standard life-history traits yield little evidence that oxidative stress
      generates strict tradeoffs. Increasing oxidative insult, however, shows a strong
      tendency to uncouple positive phenotypic correlations and, in particular, to
      reduce the correlation between reproduction and lifespan. We also found that mild
      oxidative insult results in lower levels of endogenous ROS accompanied by
      hormetic changes in lifespan, demographic aging, and reproduction that disappear
      in combined-stress treatments--consistent with the oxidative stress theory of
      aging. CONCLUSIONS: Our findings demonstrate that oxidative stress is a direct
      contributor to life-history trait variation and that traditional tradeoffs are
      not necessary to invoke oxidative stress as a mediator of relationships between
      life-history traits, supporting previous calls for revisions to theory.

PMID- 25056727
TI  - A novel 2-bp indel within Kruppel-like factor 15 gene (KLF15) and its
      associations with chicken growth and carcass traits.
AB  - 1. The Kruppel-like factor (KLF) family of zinc-finger transcription factors
      plays a critical role in cell differentiation, phenotypic modulation and
      physiologic function. KLF15 has been proposed to regulate adipogenesis and
      gluconeogenesis. The objective of this study was to establish the association
      between KLF15 gene polymorphism and chicken growth and carcass traits. 2. An
      F2resource population of Gushi chickens crossed with Anka broilers was used to
      investigate the genetic effects of the chicken KLF15 gene. A 2-bp indel mutation
      (G13781_13782del/insAG) within intron 2 was detected, and a polymerase chain
      reaction-restriction fragment length polymorphism method was developed to
      genotype the F2 individuals. 3. Association analysis showed that the Single
      Nucleotide Polymorphisms (SNP) was significantly associated with chicken growth
      and carcass traits. The chickens with the insAG/insAG genotype generally had a
      significantly higher body weight and size than other genotypes. Gene expression
      for each genotype showed that birds carrying insAG/insAG had a higher expression
      level than the other genotypes. 4. The results suggested that this polymorphic
      site may serve as a useful target for marker assisted selection of chicken growth
      and carcass traits.

PMID- 25056726
TI  - Obstructive voiding symptoms following stereotactic body radiation therapy for
      prostate cancer.
AB  - BACKGROUND: Obstructive voiding symptoms (OVS) are common following prostate
      cancer treatment with radiation therapy. The risk of urinary retention (UR)
      following hypofractionated radiotherapy has yet to be fully elucidated. This
      study sought to evaluate OVS and UR requiring catheterization following SBRT for
      prostate cancer. METHODS: Patients treated with SBRT for localized prostate
      cancer from February 2008 to July 2011 at Georgetown University were included in
      this study. Treatment was delivered using the CyberKnife(r) with doses of 35 Gy
      36.25 Gy in 5 fractions. UR was prospectively scored using the CTCAE v.3. Patient
      reported OVS were assessed using the IPSS-obstructive subdomain at baseline and
      at 1, 3, 6, 9, 12, 18 and 24 months. Associated bother was evaluated via the EPIC
      26. RESULTS: 269 patients at a median age of 69 years received SBRT with a median
      follow-up of 3 years. The mean prostate volume was 39 cc. Prior to treatment,
      50.6% of patients reported moderate to severe lower urinary track symptoms per
      the IPSS and 6.7% felt that weak urine stream and/or incomplete emptying were a
      moderate to big problem. The 2-year actuarial incidence rates of acute and late
      UR >= grade 2 were 39.5% and 41.4%. Alpha-antagonist utilization rose at one
      month (58%) and 18 months (48%) post-treatment. However, Grade 3 UR was low with
      only 4 men (1.5%) requiring catheterization and/or TURP. A mean baseline IPSS
      obstructive score of 3.6 significantly increased to 5.0 at 1 month (p < 0.0001);
      however, it returned to baseline in 92.6% within a median time of 3 months. Late
      increases in OVS were common, but transient. Only 7.1% of patients felt that weak
      urine stream and/or incomplete emptying was a moderate to big problem at two
      years post-SBRT (p = 0.6854). CONCLUSIONS: SBRT treatment caused an acute
      increase in OVS which peaked within the first month post-treatment, though acute
      UR requiring catheterization was rare. OVS returned to baseline in > 90% of
      patients within a median time of three months. Transient Late increases in OVS
      were common. However, less than 10% of patients felt that OVS were a moderate to
      big problem at two years post-SBRT.

PMID- 25056728
TI  - Nickel cobalt oxide/carbon nanotubes hybrid as a high-performance electrocatalyst
      for metal/air battery.
AB  - High-performance, low cost catalyst for oxygen reduction reaction (ORR) remains a
      big challenge. Herein, nanostructured NiCo2O4/CNTs hybrid was proposed as a high
      performance catalyst for metal/air battery for the first time. The well-formed
      NiCo2O4/CNTs hybrid was studied by steady-state linear polarization curves and
      galvanostatic discharge curves in comparison with CNTs-free NiCo2O4 and
      commercial carbon-supported Pt. Because of the synergistic effect, NiCo2O4/CNTs
      hybrid exhibited significant improvement of catalytic performance in comparison
      with NiCo2O4 or CNTs alone, even outperforming Pt/C hybrid in ORR process. In
      addition, the benefits of Ni incorporation were demonstrated by the improved
      catalytic performance of NiCo2O4/CNTs compared to Co3O4/CNTs, which should be
      attributed to improved electrical conductivity and new, highly efficient, active
      sites created by Ni cation incorporation into the spinel structure. NiCo2O4/CNTs
      hybrid could be used as a promising catalyst for high power metal/air battery. 

PMID- 25056729
TI  - Reduced nasal transport of insulin-like growth factor-1 to the mouse cerebrum
      with olfactory bulb resection.
AB  - Although the olfactory nerve is involved in nasal transport of insulin-like
      growth factor-1 (IGF-1) to the brain, to our knowledge there have been no direct
      assessments of the effects of olfactory nerve damage on this transport. To
      determine whether olfactory bulb resection resulted in reduced transport of
      nasally administered human recombinant IGF-1 (hIGF-1) to the cerebrum, we
      measured the uptake of nasally administered iodine-125 hIGF-1 ((125)I-hIGF-1) in
      the cerebrum as a percentage of that in the blood in male ICR mice subjected to
      left olfactory bulb resection (model mice) and in sham-operated male ICR mice
      (control mice). Phosphorylated extracellular signal-regulated kinase (ERK) 1/2
      (Thr202/Tyr204)/(Thr185/Tyr187) as a percentage of total ERK 1/2 in the left
      cerebrum was also assessed by using enzyme-linked immunosorbent assay after nasal
      administration of hIGF-1. Uptake of nasally administered (125)I-hIGF-1 in the
      cerebrum as a percentage of that in the blood was significantly lower in the
      model group than in the control group 30min after nasal administration of hIGF-1.
      Unilateral olfactory bulb resection prevented nasally administered hIGF-1 from
      increasing the phosphorylation of ERK 1/2 in the mouse cerebrum in vivo. These
      findings suggest that olfactory bulb damage reduces nasal transport of hIGF-1 to
      the brain in vivo. 

PMID- 25056730
TI  - The regeneration of P2 olfactory sensory neurons is selectively impaired
      following methyl bromide lesion.
AB  - The capacity of the peripheral olfactory system to recover after injury has not
      been thoroughly explored. P2-IRES-tauLacZ mice were exposed to methyl bromide,
      which causes epithelial damage and kills 90% of the P2 neurons. With subsequent
      neuronal regeneration, P2 neurons recover within their usual territory to equal
      control numbers by 1 month but then decline sharply to roughly 40% of control by
      3 months. At this time, the P2 projection onto the olfactory bulb is erroneous in
      several respects. Instead of converging onto 1 or 2 glomeruli per surface, small
      collections of P2 axons innervate multiple glomeruli at roughly the same position
      in the bulb as in controls. Within these glomeruli, the P2 axons are aggregated
      near the edge, whereas the remainder of the glomerulus contains olfactory marker
      protein (+), non-P2 axons, violating the one receptor-one glomerulus rule
      normally observed. The aggregates are denser than found in control P2-innervated
      glomeruli, suggesting that the P2 axons may not be synaptically connected. Based
      on published literature and other data, we hypothesize that P2 neurons lose out
      in an activity-based competition for synaptic territory within the glomeruli and
      are not maintained at control numbers due to a lack of trophic support from the
      bulb. 

PMID- 25056732
TI  - Transplanted human adipose tissue-derived stem cells engraft and induce
      regeneration in mice olfactory neuroepithelium in response to dichlobenil
      subministration.
AB  - We used immunodeficient mice, whose dorsomedial olfactory region was permanently
      damaged by dichlobenil inoculation, to test the neuroregenerative properties of
      transplanted human adipose tissue-derived stem cells after 30 and 60 days.
      Analysis of polymerase chain reaction bands revealed that stem cells
      preferentially engrafted in the lesioned olfactory epithelium compared with
      undamaged mucosa of untreated transplanted mice. Although basal cell
      proliferation in untransplanted lesioned mice did not give rise to neuronal cells
      in the olfactory mucosa, we observed clusters of differentiating olfactory cells
      in transplanted mice. After 30 days, and even more at 60 days, epithelial
      thickness was partially recovered to normal values, as also the
      immunohistochemical properties. Functional reactivity to odorant stimulation was
      also confirmed through electro-olfactogram recording in the dorsomedial
      epithelium. Furthermore, we demonstrated that engrafted stem cells fused with
      mouse cells in the olfactory organ, even if heterokaryons detected were too rare
      to hypothesize they directly repopulated the lesioned epithelium. The data
      reported prove that the migrating transplanted stem cells were able to induce a
      neuroregenerative process in a specific lesioned sensory area, enforcing the
      perspective that they could become an available tool for stem cell therapy. 

PMID- 25056733
TI  - [Sore throat and subcutaneous emphysema in a 71-year-old patient].
AB  - A 71-year-old woman was admitted to our emergency department due to sore throat
      and swelling of the neck and face. She had a history of chronic obstructive
      pulmonary disease grade 4 based on the Global Initiative for Chronic Obstructive
      Lung Disease (GOLD). Clinical examination revealed subcutaneous emphysema of the
      neck and face. CT scan of the thorax and abdomen showed air in the
      retroperitoneum, ascending through the mediastinum into the neck and face.
      Laparotomy confirmed the diagnosis of a retroperitoneal colon perforation due to
      colon diverticulitis. The colon was partially removed followed by a surgical
      debridement and Hartmann's procedure. The postoperative course was without
      complications, the clinical symptoms resolved rapidly. 

PMID- 25056731
TI  - Systemic modulation of serotonergic synapses via reuptake blockade or 5HT1A
      receptor antagonism does not alter perithreshold taste sensitivity in rats.
AB  - Systemic blockade of serotonin (5HT) reuptake with paroxetine has been shown to
      increase sensitivity to sucrose and quinine in humans. Here, using a 2-response
      operant taste detection task, we measured the effect of paroxetine and the 5HT1A
      receptor antagonist WAY100635 on the ability of rats to discriminate sucrose,
      NaCl, and citric acid from water. After establishing individual psychometric
      functions, 5 concentrations of each taste stimulus were chosen to represent the
      dynamic portion of the concentration-response curve, and the performance of the
      rats to these stimuli was assessed after vehicle, paroxetine (7mg/kg
      intraperitoneally), and WAY100635 (0.3mg/kg subcutaneously; 1mg/kg intravenously)
      administration. Although, at times, overall performance across concentrations
      dropped, at most, 5% from vehicle to drug conditions, no differences relative to
      vehicle were seen on the parameters of the psychometric function (asymptote,
      slope, or EC50) after drug administration. In contrast to findings in humans, our
      results suggest that modulation of 5HT activity has little impact on sucrose
      detectability at perithreshold concentrations in rats, at least at the doses used
      in this task. In the rat model, the purported paracrine/neurocrine action of
      serotonin in the taste bud may work in a manner that does not impact overt taste
      detection behavior. 

PMID- 25056734
TI  - [Oedema and haemorrhagic diathesis in a 50-year-old woman with thyrotoxicosis].
AB  - We describe the case of a 50-year-old woman who presented with tachyarrhythmia,
      mild fever, peripheral oedema, ascites, epistaxis and gastrointestinal
      haemorrhage. Blood analysis revealed hyperthyroxinaemia. Analysis of thyroid
      stimulating antibodies highlighted Graves' disease being the cause of the
      prevailing thyrotoxic crisis. Remarkable in this case of thyrotoxicosis is a
      liver affection without elevated transaminases but disturbed serum protein
      synthesis leading to hypalbuminaemic oedema and haemorrhagic complications.
      Thyrostatic treatment led to clinical response. 

PMID- 25056735
TI  - Time window for cognitive activity involved in emotional processing.
AB  - BACKGROUND: From previous studies it is becoming evident that the processing of
      unpleasant stimuli occurs early (0 to 300 ms); however, it is not clear how
      cognitive processing related to pleasant/unpleasant emotions occurs at later time
      windows (>= 300 ms). On the other hand, as evident from the previous reports, BIS
      and BAS personality traits are strongly associated with unpleasant and pleasant
      responses, respectively. Therefore, in the present study, we aim to identify the
      time window involved in human pleasant/unpleasant emotional processing by
      investigating ERP components correlated with BIS/BAS personality traits. METHODS:
      Twenty-nine men took part in the study and recording ERP during presented sounds.
      BIS/BAS score was calculated using the Japanese edition of the BIS/BAS
      questionnaire. RESULTS: Significant correlation was not observed between BIS and
      BAS scores. A significant and positive correlation was observed between N100
      amplitude and BIS score. A positive correlation was found between BAS fun seeking
      subscale score and LPP amplitude. Our findings did not contradict previous study
      results. CONCLUSIONS: Our results suggest that the processing of unpleasant
      emotions takes place early on, since N100 response was larger in high BIS
      subjects who are known to be sensitive to unpleasant emotions. LPP was larger in
      high BAS subjects who are known to be sensitive to pleasant emotions. The LPP was
      considered to be augmented because the ACC activity level during pleasant
      emotions reflected on LPP.

PMID- 25056736
TI  - Compositional insights and valorization pathways for carbonaceous material
      deposited during bio-oil thermal treatment.
AB  - This work analyses the composition, morphology, and thermal behavior of the
      carbonaceous materials deposited during the thermal treatment of bio-oil (thermal
      pyrolytic lignin-TPL). The bio-oil was obtained by flash pyrolysis of
      lignocellulosic biomass (pine sawdust), and the TPLs were obtained in the 400-700
      degrees C range. The TPLs were characterized by performing elemental analysis;
      (13)C NMR, Raman, FTIR, and X-ray photoelectron spectroscopy; SEM; and
      temperature-programmed oxidation analyzed by differential thermogravimetry and
      differential scanning calorimetry. The results are compared to a commercial
      lignin (CL). The TPLs have lower oxygen and hydrogen contents and a greater
      aromaticity and structural order than the CL material. Based on these features,
      different valorization routes are proposed: the TPL obtained at 500  degrees C is
      suitable for use as a fuel, and the TPL obtained at 700  degrees C has a suitable
      morphology and composition for use as an adsorbent or catalyst support.

PMID- 25056738
TI  - Catastrophic haemorrhage from ureterocele incision in an infant: beware of an
      associated iliac arteriovenous malformation.

PMID- 25056737
TI  - Optimal treatment for metastatic bladder cancer.
AB  - Metastatic bladder cancer is a lethal disease. Cisplatin-based chemotherapy,
      including the combination regimens gemcitabine-cisplatin and methotrexate
      vinblastine-doxorubicin-cisplatin, are the standard first-line therapies. Second
      line therapies have modest activity and no significant improvement in patient
      outcomes. Agents targeting growth, survival, and proliferation pathways have been
      added to cytotoxic therapy with limited added benefit to date. Modulating host
      immune response to cancer-associated antigens appears promising, with multiple
      new therapeutic approaches being pursued. Next-generation sequencing of invasive
      urothelial carcinoma has provided insights into the biology of this disease and
      potential actionable targets. Alterations in the receptor tyrosine kinase/Ras
      pathway and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target
      of rapamycin pathway represent potential therapeutic targets in advanced disease,
      and novel agents are in development. Recent data from the Cancer Genome Atlas
      Research Network bladder cancer cohort and other efforts suggest that mutations
      in chromatin-regulatory genes are very common in invasive bladder tumors, and are
      more frequent than in other studied tumors. The discovery of new genomic
      alterations challenges drug development to change the course of this disease. 

PMID- 25056739
TI  - Should peripheral structures be addressed in ACL reconstruction?

PMID- 25056740
TI  - Should we aim at undercorrection when doing a total knee arthroplasty?
AB  - PURPOSE: Restoration of neutral mechanical alignment is traditionally considered
      as one of the prerequisites for successful total knee replacement. The purpose of
      this study was to investigate whether a certain bias towards undercorrection
      exists with conventional total knee arthroplasty (TKA) instruments. METHODS: A
      cohort of 456 consecutive patients, who underwent the same standardised TKA with
      restoration of neutral mechanical alignment as target, was studied. Based on the
      preoperative alignment, patients were stratified into three categories: valgus,
      neutral and varus. Component and limb alignment were compared between these
      groups. RESULTS: The mean post-operative hip-knee-ankle angle was -0.7 degrees 
      (SD 2.5) in valgus knees, 0.2 degrees  (SD 1.9) in neutral knees and 2.4 degrees 
      (SD 3.9) in varus knees (p < 0.001). About 39.8% of the varus knees remained in
      >3 degrees  of varus post-operative and 20.2% of the valgus knees remained in <-3
      degrees  of valgus. A systematic unintentional undercorrection was noted in varus
      knees, which was proportional to the preoperative varus deformity and which was
      caused by varus positioning of both the femoral and tibial components. In valgus
      knees, the undercorrection was caused almost exclusively by valgus bias of the
      femoral component's position. CONCLUSION: This study showed that conventional TKA
      instruments are associated with a systematic unintentional bias towards
      undercorrection of the pre-existing deformity. The clinical relevance of this
      study is that intentionally aiming at slight undercorrection of the deformity may
      lead to excessive undercorrection in reality in case the surgeon does not
      recognise the automatic bias that already exists with standard instruments. LEVEL
      OF EVIDENCE: Therapeutic study, Level III.

PMID- 25056741
TI  - Strong induced-fit binding of viologen and pyridine derivatives in adjustable
      porphyrin cavities.
AB  - The synthesis and binding properties of new porphyrin cage compounds consisting
      of a rigid diphenylglycoluril part, which is connected via flexible
      bis(ethyleneoxy) spacers to a (metallo)porphyrin "roof", are reported. Binding of
      viologen guests and pyridine ligands in these porphyrin cages are accompanied by
      significant conformational reorganizations of the hosts. Despite these structural
      changes, association constants are still very high, revealing that not only
      receptors that bind guests according to a lock-and-key mechanism but also those
      that bind guests by an induced-fit mechanism can exhibit strong binding. 

PMID- 25056744
TI  - Environmental science and pollution sensing, monitoring, modeling, and
      remediation.

PMID- 25056743
TI  - A memory structure adapted simulated annealing algorithm for a green vehicle
      routing problem.
AB  - Currently, reduction of carbon dioxide (CO2) emissions and fuel consumption has
      become a critical environmental problem and has attracted the attention of both
      academia and the industrial sector. Government regulations and customer demands
      are making environmental responsibility an increasingly important factor in
      overall supply chain operations. Within these operations, transportation has the
      most hazardous effects on the environment, i.e., CO2 emissions, fuel consumption,
      noise and toxic effects on the ecosystem. This study aims to construct vehicle
      routes with time windows that minimize the total fuel consumption and CO2
      emissions. The green vehicle routing problem with time windows (G-VRPTW) is
      formulated using a mixed integer linear programming model. A memory structure
      adapted simulated annealing (MSA-SA) meta-heuristic algorithm is constructed due
      to the high complexity of the proposed problem and long solution times for
      practical applications. The proposed models are integrated with a fuel
      consumption and CO2 emissions calculation algorithm that considers the vehicle
      technical specifications, vehicle load, and transportation distance in a green
      supply chain environment. The proposed models are validated using well-known
      instances with different numbers of customers. The computational results indicate
      that the MSA-SA heuristic is capable of obtaining good G-VRPTW solutions within a
      reasonable amount of time by providing reductions in fuel consumption and CO2
      emissions.

PMID- 25056742
TI  - Can ornamental potted plants remove volatile organic compounds from indoor air? A
      review.
AB  - Volatile organic compounds (VOCs) are found in indoor air, and many of these can
      affect human health (e.g. formaldehyde and benzene are carcinogenic). Plants
      affect the levels of VOCs in indoor environments, thus they represent a potential
      green solution for improving indoor air quality that at the same time can improve
      human health. This article reviews scientific studies of plants' ability to
      remove VOCs from indoor air. The focus of the review is on pathways of VOC
      removal by the plants and factors affecting the efficiency and rate of VOC
      removal by plants. Laboratory based studies indicate that plant induced removal
      of VOCs is a combination of direct (e.g. absorption) and indirect (e.g.
      biotransformation by microorganisms) mechanisms. They also demonstrate that
      plants' rate of reducing the level of VOCs is influenced by a number of factors
      such as plant species, light intensity and VOC concentration. For instance, an
      increase in light intensity has in some studies been shown to lead to an increase
      in removal of a pollutant. Studies conducted in real-life settings such as
      offices and homes are few and show mixed results. 

PMID- 25056745
TI  - Temporal variations and bioaccumulation of heavy metals in different Suaeda salsa
      marshes of the Yellow River estuary, China.
AB  - To understand the temporal variations and bioaccumulation of heavy metals in the
      coastal marshes, the concentrations of heavy metals (Cr, Ni, Pb, and Cu) in the
      two Suaeda salsa marshes [middle S. salsa marsh (MM) and low S. salsa marsh (LM)]
      of the Yellow River estuary were determined from May to November in 2008 by in
      situ sampling and inductively coupled plasma mass spectrometry (ICP-MS) analysis.
      Results showed that heavy metal concentrations in S. salsa of MM and LM were
      generally in the order of Cu > Cr > Pb > Ni, while those in sediments fell in the
      order of Cr > Ni > Cu > Pb. Heavy metal concentrations of S. salsa in MM and LM
      were different, and significant differences were observed in stems (F = 4.797, p
      = 0.046) and litters (F = 6.799, p = 0.026) for Ni. Litter was the main stock of
      heavy metals, and the allocations of Cr, Ni, and Pb reached 31.25-51.31, 28.49
      42.58, and 29.55-66.79 % (in MM) and 36.73-48.60, 41.70-57.87, and 33.30-60.64 %
      (in LM), respectively. The ratios of roots/leaves (R/L) and roots/stems (R/S) for
      Cr and Ni in MM were mostly greater than 1, while those ratios in LM were mostly
      less than 1, indicating that Cr and Ni in S. salsa at LM had greater mobility
      compared with those at MM. Moreover, the [accumulation factor, AF]plant of Cr,
      Ni, Cu, and Pb in LM, especially [AF]root and [AF]stem of Cr and [AF]litter of
      Ni, was also higher than that in MM. These indicated that S. salsa grown in LM
      was more suitable for potential biomonitor or phytoremediation of Cr, Ni, Cu, and
      Pb if intertidal sediments were seriously contaminated with an increase of
      pollutant loading (especially heavy metals) in the Yellow River estuary. The use
      of biomonitor (S. salsa) living and growing in LM could yield valuable
      information not only on the presence of anthropogenic stressors, but, more
      importantly, on the adverse influence the stressors are having on the
      environment.

PMID- 25056747
TI  - Factors affecting degradation of dimethyl sulfoxide (DMSO) by fluidized-bed
      Fenton process.
AB  - In this study, the target compound is dimethyl sulfoxide (DMSO), which is used as
      a photoresist stripping solvent in the semiconductor and thin-film transistor
      liquid crystal display (TFT-LCD) manufacturing processes. The effects of the
      operating parameters (pH, Fe(2+) and H2O2 concentrations) on the degradation of
      DMSO in the fluidized-bed Fenton process were examined. This study used the Box
      Behnken design (BBD) to investigate the optimum conditions of DMSO degradation.
      The highest DMSO removal was 98 % for pH 3, when the H2O2 to Fe(2+) molar ratio
      was 12. At pH 2 and 4, the highest DMSO removal was 82 %, when the H2O2 to Fe(2+)
      molar ratio was 6.5. The correlation of DMSO removal showed that the effect of
      the parameters on DMSO removal followed the order Fe(2+) > H2O2 > pH. From the
      BBD prediction, the optimum conditions were pH 3, 5 mM of Fe(2+), and 60 mM of
      H2O2. The difference between the experimental value (98 %) and the predicted
      value (96 %) was not significant. The removal efficiencies of DMSO, chemical
      oxygen demand (COD), total organic carbon (TOC), and iron in the fluidized-bed
      Fenton process were higher than those in the traditional Fenton process.

PMID- 25056748
TI  - Experimental study of humic acid degradation and theoretical modelling of
      catalytic ozonation.
AB  - The efficiency of TiO2 as a catalyst in the ozonation of humic acid (HA) was
      evaluated in a comprehensive manner. Ozonation, catalytic ozonation and
      adsorption experiments were conducted using both synthetic HA solution and
      natural water. HA degradation was evaluated in terms of DOC, VIS400 and UV254. It
      was shown that the addition of catalyst positively affects the mechanism of
      ozonation. An increase in HA degradation was observed for all these parameters.
      The impact of catalyst dose and initial pH value of HA on the efficacy of
      catalytic ozonation was investigated. The highest removal efficiencies were
      achieved with the dose of 1 g l(-1) of TiO2 (Degussa P-25) and in the acidic pH
      region. The catalytic ozonation process was efficient also on natural water
      component although not at the same level as it was on synthetic water. The
      adsorptive feature of P-25 was considered to have a clear evidence of the
      catalytic ozonation mechanism. The mechanism of catalysis on the surface of metal
      oxides was elucidated with the help of quantum-chemical calculations. In the
      framework of Density Function Theory (DFT), the O3 decomposition was calculated
      in the catalytic and non-catalytic processes. Donor-acceptor properties of the
      frontier (highest occupied and lowest unoccupied molecular orbitals, HOMO/LUMO)
      orbitals are discussed. Electron density distribution and reaction mechanism of
      superoxide particles formation, which participate in the process of HA ozonation
      are analyzed. 

PMID- 25056746
TI  - Characterization and cadmium-resistant gene expression of biofilm-forming marine
      bacterium Pseudomonas aeruginosa JP-11.
AB  - Biofilm-forming marine bacterium Pseudomonas aeruginosa JP-11 was isolated from
      coastal marine sediment of Paradeep Port, Odisha, East Coast, India, which
      resisted up to 1,000 ppm of cadmium (Cd) as cadmium chloride in aerobic
      conditions with a minimal inhibitory concentration of 1,250 ppm. Biomass and
      extracellular polymeric substances (EPS) secreted by the cells effectively
      removed 58.760 +/- 10.62 and 29.544 +/- 8.02 % of Cd, respectively. The
      integrated density of the biofilm-EPS observed under fluorescence microscope
      changed significantly (P <= 0.05) in the presence of 50, 250, 450, 650 and 850
      ppm Cd. ATR-FTIR spectroscopy showed a peak at 2,365.09/cm in the presence of 50,
      250, 450 and 650 ppm Cd which depicts the presence of sulphydryl group (-SH)
      within the EPS, whereas, a peak shift to 2,314.837/cm in the presence of 850 ppm
      Cd suggested the major role of this functional group in the binding with cadmium.
      On exposure to Cd at 100, 500 and 1,000 ppm, the expression profiles of cadmium
      resistance gene (czcABC) in the isolate showed an up-regulation of 3.52-, 17- and
      24-fold, respectively. On the other hand, down-regulation was observed with
      variation in the optimum pH (6) and salinity (20 g l(-1)) level. Thus, the
      cadmium resistance gene expression increases on Cd stress up to the tolerance
      level, but an optimum pH and salinity are the crucial factors for proper
      functioning of cadmium resistance gene.

PMID- 25056749
TI  - Effect of operational parameters on heavy metal removal by electrocoagulation.
AB  - In the present paper, the performance of electrocoagulation (EC) for the
      treatability of mixed metals (chromium (Cr), copper (Cu), lead (Pb), nickel (Ni),
      and zinc (Zn)) from metal plating industrial wastewater (EPW) has been
      investigated. The study mainly focused on the affecting parameters of EC process,
      such as electrode material, initial pH, distance between electrodes, electrode
      size, and applied voltage. The pH 8 is observed to be the best for metal removal.
      Fe-Fe electrode pair with 1-cm inter-electrode distance and electrode surface
      area of 40 cm(2) at an applied voltage of 8 V is observed to more efficient in
      the metal removal. Experiments have shown that the maximum removal percentage of
      the metals like Cr, Ni, Zn, Cu, and Pb are reported to be 96.2, 96.4, 99.9, 98,
      and 99.5 %, respectively, at a reaction time of 30 min. Under optimum conditions,
      the energy consumption is observed to be 51.40 kWh/m(3). The method is observed
      to be very effective in the removal of metals from electroplating effluent.

PMID- 25056750
TI  - Release of agronomical nutrient from zeolitite substrate containing phosphatic
      waste.
AB  - The principal plant nutrients are phosphorous, nitrogen and potassium. Among
      these compounds, phosphorous is the most critical: it reacts rapidly, becoming an
      insoluble compound. The combination of zeolitites with phosphate materials
      (zeoponic substrate) agrees to a gradual and controlled phosphorous release in
      soils: phosphorous for plant uptake is released by the combination of dissolution
      and ion-exchange reactions. Animal bone ashes, rich in phosphorous and leached
      alone, release little amounts of soluble phosphorous and a great deal of alkaline
      sodium and potassium. Concerning chabazitic-zeolitite, it encourages a both
      gradual and growing soluble phosphorous release from animal bone ashes, in
      accordance with clinoptilolitic- and phillipsitic-zeolitite abilities; in
      particular, that release increases, thanks to both a higher zeolitite/bone ash
      ratio and ammonium enrichment of zeolitite. The use of zeolitite is
      environmentally sustainable in Italy because large amounts of deposits of
      zeolitite were present in Italy.

PMID- 25056752
TI  - The purple Codex Rossanensis: spectroscopic characterisation and first evidence
      of the use of the elderberry lake in a sixth century manuscript.
AB  - This paper presents the results obtained during the measurements campaign started
      in June 2012 and ended in November 2013 on the invaluable purple Codex
      Rossanensis, sixth century, one of the oldest surviving illuminated manuscripts
      of the New Testament. The tasks of the chemistry laboratory were to answer a
      variety of questions posed both by historians and restorers, concerning the
      materials used in a previous restoration, the composition of the pictorial
      palette and the different inks and to determine which colouring material had been
      applied to dye the parchment support. It was also requested to determine the
      state of preservation of the manuscript, as a result of its interactions with the
      environment in which the manuscript had been stored and the vicissitudes
      experienced during its life (fire, previous restoration, exhibition). The
      spectroscopic analyses performed by micro-Raman, micro-Fourier transform infrared
      and X-ray fluorescence allowed to fill a gap in the knowledge of the pictorial
      materials used in the Early Middle Ages. The pictorial palette, the inks, the dye
      applied to obtain the purple parchments, the support and the materials used in
      the previous restoration treatment executed in 1917-19 were fully characterised.
      Moreover, to the author's knowledge, the article shows the first experimental
      evidence of the use of the elderberry lake in a sixth century-illuminated
      manuscript. The lake was characterised by Raman spectroscopy.

PMID- 25056751
TI  - A fingerprint analysis method for characterization of dissolved organic matter in
      secondary effluents of municipal wastewater treatment plant.
AB  - Dissolved organic matter (DOM) in wastewater and reclaimed water is related to
      water quality, safety, and treatability. In this study, DOM was characterized
      through a fingerprint analysis method for DOM characterization using resin
      fractionation followed by size exclusion chromatography (SEC). Resin
      fractionation was used in the first step to divide the DOM in water samples into
      six resin fractions, namely, hydrophobic acids (HOA), hydrophobic bases (HOB),
      hydrophobic neutrals (HON), hydrophilic acids (HIA), hydrophilic bases (HIB), and
      hydrophilic neutrals (HIN). SEC analysis was then performed to separate each
      resin fraction into several (n) subfractions with different molecular weights
      (MW). Thus, the total DOM in the water sample was fractionated into 6n
      subfractions. After quantification of each subfraction by dissolved organic
      carbon (DOC), a fingerprint graph was constructed to express the distribution of
      DOM in the subfractions. The fingerprint analysis method was applied to a
      secondary effluent sample during ozonation. Ozonation (dose of 10 mg L(-1))
      removed the DOC only by 8 % and reduced UV254 of the sample by 36 %. Fingerprint
      graphs also revealed that the resin fractions changed quite limitedly but
      transformation of subfractions occurred notably.

PMID- 25056753
TI  - Microbial contamination of drinking water in Pakistan--a review.
AB  - Water pollution with pathogenic microorganisms is one of the serious threats to
      human health, particularly in developing countries. The main objective of this
      article is to highlight microbial contamination of drinking water, the major
      factors responsible for microbial contamination, and the resulting health
      problems in Pakistan. Furthermore, this study will be helpful for researchers and
      administrative agencies to initiate relevant studies and develop new policies to
      protect further deterioration of water supply with pathogenic microbes and ensure
      clean and safe drinking water to the public in Pakistan. In Pakistan, water at
      the source, in the distribution network, and at the consumer tap is heavily
      polluted with coliforms and fecal coliforms all over the country. An overview of
      more than 7,000 water samples reviewed here reveals that an average of over 71
      and 58 % samples in the country was contaminated with total coliforms and fecal
      coliforms, respectively. Drinking water contamination accounts for 20 to 40 % of
      all diseases in the country, which causes national income losses of Rs 25-58
      billion annually (US$0.25-0.58 billion, approximately 0.6-1.44 % of the country's
      GDP). Improper disposal of industrial and municipal wastes is the most important
      factor responsible for water pollution in the country followed by cross
      contamination due to old and leaking pipes and lack of water filtration and
      disinfection facilities. There is an urgent need for emergency steps to stop
      further deterioration of water quality and improve the existing water quality so
      as to protect the public from widespread waterborne diseases.

PMID- 25056754
TI  - Effects of high ammonium level on biomass accumulation of common duckweed Lemna
      minor L.
AB  - Growing common duckweed Lemna minor L. in diluted livestock wastewater is an
      alternative option for pollutants removal and consequently the accumulated
      duckweed biomass can be used for bioenergy production. However, the biomass
      accumulation can be inhibited by high level of ammonium (NH4 (+)) in non-diluted
      livestock wastewater and the mechanism of ammonium inhibition is not fully
      understood. In this study, the effect of high concentration of NH4 (+) on L.
      minor biomass accumulation was investigated using NH4 (+) as sole source of
      nitrogen (N). NH4 (+)-induced toxicity symptoms were observed when L. minor was
      exposed to high concentrations of ammonium nitrogen (NH4 (+)-N) after a 7-day
      cultivation. L. minor exposed to the NH4 (+)-N concentration of 840 mg l(-1)
      exhibited reduced relative growth rate, contents of carbon (C) and photosynthetic
      pigments, and C/N ratio. Ammonium irons were inhibitory to the synthesis of
      photosynthetic pigments and caused C/N imbalance in L. minor. These symptoms
      could further cause premature senescence of the fronds, and restrain their
      reproduction, growth and biomass accumulation. L. minor could grow at NH4 (+)-N
      concentrations of 7-84 mg l(-1) and the optimal NH4 (+)-N concentration was 28 mg
      l(-1).

PMID- 25056756
TI  - Use of graphite as a highly reversible electrode with superior cycle life for
      sodium-ion batteries by making use of co-intercalation phenomena.
AB  - Although being the standard anode material in lithium-ion batteries (LIBs),
      graphite so far is considered to fail application in sodium-ion batteries (NIBs)
      because the Na-C system lacks suitable binary intercalation compounds. Here we
      show that this limitation can be circumvented by using co-intercalation phenomena
      in a diglyme-based electrolyte. The resulting compound is a stage-I ternary
      intercalation compound with an estimated stoichiometry of Na(diglyme)2C20.
      Highlights of the electrode reaction are its high energy efficiency, the small
      irreversible loss during the first cycle, and a superior cycle life with
      capacities close to 100 mAh g(-1) for 1000 cycles and coulomb efficiencies
      >99.87%. A one-to-one comparison with the analogue lithium-based cell shows that
      the sodium-based system performs better and also withstands higher currents.

PMID- 25056758
TI  - Zero-field slow magnetic relaxation in a uranium(III) complex with a radical
      ligand.
AB  - [U(Tp(Me2))2(bipy)], a uranium(III) complex with a radical bipyridine ligand
      which has magnetic properties with contributions from both the ligand and the
      metal, presents slow relaxation of the magnetisation at low temperatures, already
      under zero static magnetic field, and energy barriers slightly above the non
      radical analogues.

PMID- 25056757
TI  - In vitro evaluation of the effects of perfluorooctanesulfonic acid (PFOS) and
      perfluorooctanoic acid (PFOA) on IL-2 production in human T-cells.
AB  - Perfluorinated compounds, such as perfluorooctane sulfonate (PFOS) and
      perfluorooctanoic acid (PFOA), have been shown to alter various immune functions
      suggesting they are immunotoxic. This study assessed the effects of PFOS and PFOA
      on interleukin (IL)-2 production in the human Jurkat T-cell line and PFOS in
      healthy human primary T cells. Jurkat cells were stimulated with
      phytohemagglutinin (PHA)/phorbol myristate acetate (PMA), anti CD-3/anti CD-28,
      or anti CD-3, and dosed with 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 75, or 100 ug ml(
      1) PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 ug ml(-1) PFOA. Jurkat
      cells stimulated with PHA/PMA or anti CD-3 exhibited decreased IL-2 production
      beginning at 50 ug PFOS ml(-1) and 5 ug PFOS ml(-1) respectively, but stimulation
      with anti-CD3/anti-CD28 resulted in no changes compared with the control.
      Addition of the PPAR-alpha antagonist GW6471 to PFOS-dosed cells stimulated with
      PHA/PMA resulted in decreases in IL-2 production starting at 50 ug PFOS ml(-1),
      which suggests PFOS affected T-cell IL-2 production via PPAR-alpha-independent
      mechanisms. Exposure to PFOA, PFOA + GW6471, or PFOS + PFOA in Jurkat cells
      resulted in no significant differences in IL-2 production. In vitro dosing
      studies using healthy primary human CD4+ T cells were consistent with the Jurkat
      results. These data demonstrated that PFOA did not impact IL-2 production, but
      PFOS suppressed IL-2 production in both a human cell line and human primary cells
      at dose levels within the high end of the human exposure range. A decrease in IL
      2 production is characteristic of autoimmune diseases such as systemic lupus
      erythematosus and should be further investigated.

PMID- 25056759
TI  - Potential effects of NPC1L1 polymorphisms in protecting against clinical disease
      in a chinese family with sitosterolaemia.
AB  - Sitosterolaemia is caused by mutations in either ABCG5 or ABCG8. Chinese and
      Japanese individuals usually have mutations in ABCG5. We herein report a known
      and a novel mutation in ABCG8 and their potential interaction with NPC1L1
      polymorphisms in a Chinese family with sitosterolaemia. We sequenced ABCG5 and
      ABCG8 and measured the levels of plasma plant sterols in a 15-year-old Chinese
      girl with clinical sitosterolaemia (xanthomas with elevated low-density
      lipoprotein cholesterol (LDL-C) and plant sterols) and her apparently healthy
      family members. NPC1L1 was sequenced in the genetically affected sibling and
      other family members. A known mutation, c.490C>T (p. Arg164(*)), in exon 4 and a
      novel mutation, c.1949T>G (p.Leu650Arg), in exon 13 of ABCG8 were detected in the
      proband and her sister, who had elevated sterols but low LDL-C levels and no
      xanthomas. The genetically affected sister, but not the proband, carried two
      additional heterozygous changes in NPC1L1 (rs2072183 C>G, rs2301935 A>C), which
      were inherited from the mother, who also had a low LDL-C level. In this study, we
      detected a known and a novel mutation in ABCG8 in a Chinese patient with
      sitosterolaemia. The same mutations were found in her clinically normal sister,
      suggesting that the contrasting features with the proband may be related to
      different variants in NPC1L1 and/or some other undetermined lipid-related genetic
      factors. 

PMID- 25056760
TI  - Relationships between nocturnal intermittent hypoxia, arterial stiffness and
      cardiovascular risk factors in a community-based population: the Toon health
      study.
AB  - AIM: Nocturnal intermittent hypoxia (NIH), a primary marker of obstructive sleep
      apnea, has increasingly been linked with cardiovascular morbidity and mortality.
      The purpose of this study was to investigate the association between NIH and
      arterial stiffness as measured according to the cardio-ankle vascular index
      (CAVI) based on cardiovascular risk factors in a Japanese community-dwelling
      population. METHODS: We conducted a cross-sectional study in Toon city among 684
      men and 1,241 women 30-79 years of age. The severity of NIH was defined as mild
      or moderate-to-severe according to five or 15 events/hour on the 3% oxygen
      desaturation index (ODI), respectively. Increased arterial stiffness was
      diagnosed according to a CAVI of >=9. RESULTS: The number of subjects with no,
      mild and moderate-to-severe NIH was 1,348 (70%), 451 (23%) and 126 (7%),
      respectively. Increased arterial stiffness was detected in 21.9% of the
      participants. The multivariable-adjusted odds ratio (95% CI) of severe NIH
      related to an increased CAVI in comparison with a 3% ODI of <5 was 1.36 (0.82
      2.23). The stratified logistic regression analysis showed that the multivariable
      adjusted OR of severe NIH for an increased CAVI was remarkably increased in the
      individuals with a BMI of >=25 (OR=2.53, 1.08-5.96; p=0.03). An interaction test
      showed a trend for an overweight status to be a modifier of the association
      between OSA and increased arterial stiffness (p=0.05). CONCLUSIONS: NIH has a
      tendency to promote increased arterial stiffness as measured according to the
      CAVI, especially in overweight subjects.

PMID- 25056761
TI  - Relationship between SLCO1B3 and ABCA3 polymorphisms and imatinib response in
      chronic myeloid leukemia patients.
AB  - BACKGROUND: Genetic variations in membrane transporters may contribute to
      imatinib mesylate (IM) resistance in chronic myeloid leukemia (CML). Objective To
      investigate the relationship between SLCO1B3, SLCO1A2, and ABCA3 polymorphisms
      and IM response in CML patients. METHODS: Patients in chronic phase CML (N = 118)
      were studied. All patients were treated with a standard dose of IM (400 mg/day)
      and classified into one of the two groups according to their responses. Major
      molecular response (MMR) and complete molecular response (CMR) were evaluated.
      Criteria for response failure were established according to European LeukemiaNet
      (2009). Analysis of the SLCO1B3 c.334T > G (rs4149117) and c.699G > A
      (rs7311358), SLCO1A2 c.516A > C (rs11568563) and c.-62-361G > A (rs3764043), and
      ABCA3 c.1755C > G (rs323043) and c.4548-191C > A (rs150929) polymorphisms was
      carried out by real-time polymerase chain reaction. RESULTS: SLCO1A2 and ABCA3
      polymorphisms have similar frequencies between responders and non-responders.
      SLCO1B3 699GG and 344TT genotypes were more frequent in the responder group
      (63.8%) than in the non-responder group (44.7%, P = 0.042). Furthermore, carriers
      of 699GA/AA and 334TG/GG genotypes presented a higher probability of not
      responding to the standard dose of IM (odds ratio: 2.17; 95% confidence interval:
      1.02-4.64, P = 0.04). Poor CMR for ABCA3 4548-91C > A was observed in patients
      with the CC/CA genotype when compared to AA carriers in the responder group (P =
      0.014). CONCLUSIONS: SLCO1B3 699GG and 344TT genotypes are associated with non
      response to IM, while ABCA3 4548-91 CC/CA genotypes are related to poor CMR in
      CML patients treated with standard-dose imatinib.

PMID- 25056762
TI  - The role of reflection in the effects of community service on adolescent
      development: a meta-analysis.
AB  - This meta-analysis assessed the effect of community service on adolescent
      development and the moderation of this effect by reflection, community service,
      and adolescent characteristics to explicate the mechanisms underlying community
      service effects. Random effects analyses, based on 49 studies (24,477
      participants, 12-20 years old), revealed that community service had positive
      effects on academic, personal, social, and civic outcomes. Moderation analyses
      indicated that reflection was essential; the effect for studies that include
      reflection was substantial (mean ES = .41) while community service in the absence
      of reflection yielded negligible benefits (mean ES = .05). Effects increased when
      studies include more frequent reflection and community service, reflection on
      academic content, and older adolescents. These findings have implications for
      understanding and improving community service. 

PMID- 25056763
TI  - Organocatalysed multicomponent synthesis of pyrazolidinones: Meldrum's acid
      approach.
AB  - We discovered a novel organocatalysed multicomponent domino Knoevenagel-aza
      Michael-cyclocondensation reaction leading to an unprecedented straightforward
      synthesis of 1,5-diazabicyclo[3.3.0]octane-2,6-diones. The specific capability of
      the (DHQ)2PHAL organocatalyst in this process was also highlighted to eventually
      furnish the corresponding bicyclopyrazolidinones with up to 96 : 4 er. 

PMID- 25056764
TI  - Reducing racial disparity in colorectal cancer burden.

PMID- 25056765
TI  - Idiopathic high-flow priapism due to bilateral internal pudendal artery shunting.

PMID- 25056766
TI  - TVT versus laparoscopic mesh colposuspension: 5-year follow-up results of a
      randomized clinical trial.
AB  - INTRODUCTION AND HYPOTHESIS: Before the introduction of the tension-free vaginal
      tape (TVT) procedure for the treatment of female stress urinary incontinence, the
      colposuspension operation was regarded as the "gold standard" procedure. The
      laparoscopic variant of the colposuspension was introduced as a less invasive
      operation. The aim of the present trial was to compare the new minimally invasive
      TVT procedure with laparoscopic mesh colposuspension (LCM). METHODS: A
      multicenter randomized clinical trial conducted in six public hospitals in
      Finland including primary cases of stress incontinence. Objective treatment
      success criteria were a negative stress test and no retreatment for stress
      incontinence. Patient satisfaction was assessed by Patients Global Impression of
      Improvement, a visual analog scale, and the Urinary Incontinence Severity Score.
      RESULTS: Of 128 randomized patients, 121 underwent the allocated operation. At
      the 5-year follow-up 77 % in the TVT group and 84 % in the LCM group could be
      assessed according to the protocol. The objective cure rate was significantly
      higher in the TVT group (94 %) than in the LCM group (78 %). Subjective treatment
      satisfaction (completely satisfied with the procedure) was significantly higher
      in the TVT group (64 %) than in the LCM group (51 %). CONCLUSIONS: By per
      protocol analysis both objective and subjective cure rates were significantly
      higher in the TVT group than in the LCM group. If cases that were lost to follow
      up were regarded as failures, the intension-to-treat analysis found no difference
      between the groups.

PMID- 25056767
TI  - Outcomes of trocar-guided Gynemesh PSTM versus single-incision trocarless
      PolyformTM transvaginal mesh procedures.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to compare rates of
      success, mesh exposure, and surgical re-intervention after trocar-guided Gynemesh
      PSTM and trocarless PolyformTM transvaginal mesh procedures. METHODS: We
      conducted a retrospective cohort study of all transvaginal mesh procedures
      performed at our centers between January 2008 and May 2012. Multiple logistic
      regression models were used to explore the binary outcomes of objective and
      subjective success rates, as well as mesh exposure and re-intervention rates,
      between the two procedures after adjustment for patient's age, parity, body mass
      index, smoking status, previous hysterectomy, previous prolapse surgery, and
      follow-up time. RESULTS: We included 103 transvaginal mesh procedures (47 trocar
      guided Gynemesh PSTM and 56 trocarless PolyformTM). In both groups, Pelvic Organ
      Prolapse Quantification (POP-Q) scores were significantly improved after the
      procedure. Median follow-up was 340 days and interquartile range (IQR) 152-644.
      Objective success rates were 55.3 % (26/47) in the trocar group and 60.7 %
      (34/56) in the trocarless group (p = 0.9), whereas subjective success was 83.0 %
      (39/47) and 94.6 % (53/56), respectively (p = 0.1). The adjusted odds of
      developing mesh exposure were significantly less after trocarless transvaginal
      mesh procedures compared to trocar-guided ones [odds ratio (OR) 0.16, 95 %
      confidence interval (CI) 0.03-0.97]. Surgical re-interventions, aimed mostly at
      treating recurrent prolapse, mesh exposure, and latent stress urinary
      incontinence, were also significantly less frequent after trocarless procedures
      [5 patients (8.9 %) requiring re-intervention versus 15 (31.9 %), respectively,
      adjusted OR 0.15, 95 % CI 0.04-0.60]. CONCLUSIONS: Trocar-guided Gynemesh PSTM
      and trocarless PolyformTM transvaginal mesh systems result in similar objective
      and subjective success rates. The newer PolyformTM mesh results in significantly
      fewer mesh exposures and surgical re-interventions.

PMID- 25056768
TI  - Facilitators and barriers to the active participation of clients with serious
      mental illnesses in medication decision making: the perceptions of young adult
      clients.
AB  - The active participation of young adults with serious mental illnesses (SMI) in
      making decisions about their psychotropic medications is beneficial to their care
      quality and overall health. Many however report not expressing treatment
      preferences to psychiatrists. Qualitative methods were used to interview 24 young
      adults with SMI about their experiences making medication decisions with their
      psychiatrists. An inductive analytic approach was taken to identifying conceptual
      themes in the transcripts. Respondents reported that the primary facilitators to
      active participation were the psychiatrist's openness to the client's
      perspective, the psychiatrist's availability outside of office hours, the support
      of other mental health providers, and personal growth and self-confidence of the
      young adults. The primary barriers to active participation reported were the
      resistance of the psychiatrist, the lack of time for consultations, and limited
      client self-efficacy. Young adults with SMI can be active participants in making
      decisions about their psychiatric treatment. 

PMID- 25056769
TI  - Convenient synthesis of functionalized bis-ureidopyrimidinones based on thiol-yne
      reaction.
AB  - The preparation of functionalized bis-ureidopyrimidinones (Bis-UPy) through the
      thiol-yne reaction is described. Various Bis-UPys with different functional
      groups were synthesized by using the readily available functionalized alkynes and
      UPy-thiol to affirm the simplicity and versatility of the methodology. 

PMID- 25056771
TI  - Catalytic enantioselective C-H functionalization of alcohols by redox-triggered
      carbonyl addition: borrowing hydrogen, returning carbon.
AB  - The use of alcohols and unsaturated reactants for the redox-triggered generation
      of nucleophile-electrophile pairs represents a broad, new approach to carbonyl
      addition chemistry. Discrete redox manipulations that are often required for the
      generation of carbonyl electrophiles and premetalated carbon-centered
      nucleophiles are thus avoided. Based on this concept, a broad, new family of
      enantioselective C-C coupling reactions that are catalyzed by iridium or
      ruthenium complexes have been developed, which are summarized in this Minireview.

PMID- 25056772
TI  - The deposition and characterization of starch in Brachypodium distachyon.
AB  - Brachypodium distachyon is a non-domesticated cereal. Nonetheless, Brachypodium
      was recently introduced as a model plant for temperate cereals. This study
      compares grain starch metabolism in Brachypodium and barley (Hordeum vulgare). In
      Brachypodium, we identified and annotated 28 genes involved in starch metabolism
      and identified important motifs including transit peptides and putative
      carbohydrate-binding modules (CBMs) of the families CBM20, CBM45, CBM48, and
      CBM53. Starch content was markedly lower in Brachypodium grains (12%) compared to
      barley grains (47%). Brachypodium starch granules were doughnut shaped and
      bimodally distributed into distinct small B-type (2.5-10 um) and very small C
      type (0.5-2.5 um) granules. Large A-type granules, typical of cereals, were
      absent. Starch-bound phosphate, important for starch degradation, was 2-fold
      lower in Brachypodium compared with barley indicating different requirements for
      starch mobilization. The amylopectin branch profiles were similar and the amylose
      content was only slightly higher compared with barley cv. Golden Promise. The
      crystallinity of Brachypodium starch granules was low (10%) compared to barley
      (20%) as determined by wide-angle X-ray scattering (WAXS) and molecular disorder
      was confirmed by differential scanning calorimetry (DSC). The expression profiles
      in grain for most genes were distinctly different for Brachypodium compared to
      barley, typically showing earlier decline during the course of development, which
      can explain the low starch content and differences in starch molecular structure
      and granule characteristics. High transitory starch levels were observed in
      leaves of Brachypodium (2.8% after 14h of light) compared to barley (1.9% after
      14h of light). The data suggest important pre-domesticated features of cereals.

PMID- 25056774
TI  - TEF-7A, a transcript elongation factor gene, influences yield-related traits in
      bread wheat (Triticum aestivum L.).
AB  - In this study, TaTEF-7A, a member of the transcript elongation factor gene
      family, and its flanking sequences were isolated. TaTEF-7A was located on
      chromosome 7A and was flanked by markers Xwmc83 and XP3156.3. Subcellular
      localization revealed that TaTEF-7A protein was localized in the nucleus. This
      gene was expressed in all organs, but the highest expression occurred in young
      spikes and developing seeds. Overexpression of TaTEF-7A in Arabidopsis thaliana
      produced pleiotropic effects on vegetative and reproductive development that
      enhanced grain length, silique number, and silique length. No diversity was found
      in the coding region of TaTEF-7A, but 16 single nucleotide polymorphisms and
      Indels were detected in the promoter regions of different cultivars. Markers
      based on sequence variations in the promoter regions (InDel-629 and InDel-604)
      were developed, and three haplotypes were identified based on those markers.
      Haplotype-trait association analysis of the Chinese wheat mini core collection
      revealed that TaTEF-7A was significantly associated with grain number per spike.
      Phenotyping of near-isogenic lines (NILs) confirmed that TaTEF-7A increases
      potential grain yield and yield-related traits. Frequency changes in favoured
      haplotypes gradually increased in cultivars released in China from the 1940s.
      Geographic distributions of favoured haplotypes were characterized in six major
      wheat production regions worldwide. The presence of Hap-7A-3, the favoured
      haplotype, showed a positive correlation with yield in a global set of breeding
      lines. These results suggest that TaTEF-7A is a functional regulatory factor for
      grain number per spike and provide a basis for marker-assisted selection.

PMID- 25056775
TI  - A dispersive liquid-liquid micellar microextraction for the determination of
      pharmaceutical compounds in wastewaters using ultra-high-performace liquid
      chromatography with DAD detection.
AB  - A dispersive liquid-liquid micellar microextraction (DLLMME) method coupled with
      ultra-high-performance liquid chromatography (UHPLC) using Diode Array Detector
      (DAD) detector was developed for the analysis of five pharmaceutical compounds of
      different nature in wastewaters. A micellar solution of a surfactant,
      polidocanol, as extraction solvent (100 MUL) and chloroform as dispersive solvent
      (200 MUL) were used to extract and preconcentrate the target analytes. Samples
      were heated above critical temperature and the cloudy solution was centrifuged.
      After removing the chloroform, the reduced volume of surfactant was then injected
      in the UHPLC system. In order to obtain high extraction efficiency, the
      parameters affecting the liquid-phase microextraction, such as time and
      temperature extraction, ionic strength and surfactant and organic solvent volume,
      were optimized using an experimental design. Under the optimized conditions, this
      procedure allows enrichment factors of up to 47-fold. The detection limit of the
      method ranged from 0.1 to 2.0 ug/L for the different pharmaceuticals. Relative
      standard deviations were <26% for all compounds. The procedure was applied to
      samples from final effluent collected from wastewater treatment plants in Las
      Palmas de Gran Canaria (Spain), and two compounds were measured at 67 and 113
      ug/L in one of them.

PMID- 25056776
TI  - Formation and stability of 4-(hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone
      glucuronide, a stable form of reactive intermediate produced from 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, in mice.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific
      nitrosamine, induced lung tumors in rodents and is likely involved in human lung
      cancer. 4-(Hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (HO-methyl NNK)
      glucuronide, a glucuronide of the reactive intermediate of NNK, has been
      identified in rats. The aim of this study is to estimate the role of HO-methyl
      NNK glucuronide in the tumorigenic effects of NNK. We investigated the urinary
      excretion and tissue distribution of HO-methyl NNK glucuronide in A/J mice, which
      are susceptible to NNK carcinogenesis, and C57BL/6J mice, which are resistant to
      NNK carcinogenesis. The cumulative urinary excretion of the HO-methyl NNK
      glucuronide in the C57BL/6J mice was more than 20 times higher than in the A/J
      mouse urine. Tissue concentrations of HO-methyl NNK glucuronide were also higher
      in the C57BL/6J mice than in the A/J mice. Assessment of the stability of HO
      methyl NNK glucuronide in liver homogenates at physiological pH conditions showed
      that more than 60% of the glucuronide remained until 2 hr of incubation. These
      results suggested that HO-methyl NNK glucuronide is likely to be a detoxified
      metabolite and could be one reason for differences in the susceptibility to NNK
      tumorigenesis between the two strains. Once HO-methyl NNK is formed in tissues,
      C57BL/6J mice have a high ability to form HO-methyl NNK glucuronide so that HO
      methyl NNK, the reactive intermediate formed from NNK, is readily excreted in
      urine as a stable form. 

PMID- 25056777
TI  - Purification and characterization of five snake venom metalloproteinases from
      Egyptian Echis pyramidum pyramidum venom.
AB  - New five P-III snake venom metalloproteinases (SVMPs): EpyB2 (62 kDa), EpyB3
      (62+23 kDa), EpyB4 (60 kDa), EpyB5 (67 kDa) and EpyB6 (66 kDa) of the most
      dangerous viper, Echis pyramidum pyramidum (Epy), were purified and characterized
      in a set of biochemical assays. The SVMPs were purified by applying a protocol of
      two successive chromatographic steps. Three purified SVMPs "EpyB2, EpyB4, and
      EpyB5" have hemorrhagic activity with MHDs, 7 MUg, 7.6 MUg and 15 MUg,
      respectively; furthermore, they have high preference towards fibronectin,
      collagen, gelatin, fibrin and hemoglobin substrates compared with non-hemorrhagic
      SVMPs (EpyB3 and EpyB6). All the purified SVMPs showed remarkable thermal and pH
      stability, inhibited by metalloproteinase inhibitors and Zn(2+), Mn(2+), Ni(2+),
      Co(2+), Cu(2+), and Hg(2+). The purified SVMPs act as alpha-fibrinogenases,
      prothrombin activators and procoagulants. In conclusion, Epy venom has multiple
      SVMPs that are responsible for hemorrhagic events and thus represent a
      significant health hazard for victims of envenomation, however, they may be
      useful for treating diseases involving abnormal blood clot formation. 

PMID- 25056779
TI  - Immunosuppressive potential of bardoxolone methyl using a modified murine local
      lymph node assay (LLNA).
AB  - 2-Cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me;
      bardoxolone methyl) is one of the synthetic oleanane triterpenoids (SOs). It is
      known that it is the strongest Nrf2/ARE signaling inducer of SOs and slightly
      inhibits immune response. Little was known about the immunomodulatory action of
      CDDO-Me in vivo. We assessed its immunosuppressive potential by using the
      modified mouse lymph node assay (LLNA) including immunosuppression-related gene
      expression analysis. In the modified LLNA, CDDO-Me showed a significant decrease
      in lymph node weight and changes in expressions of the immunosuppression-related
      genes, Zfp459 and Fmo2. It has been already reported that a decrease in lymph
      node weight was induced by several types of immunosuppressive chemicals such as
      calcineurin inhibitors, antimetabolites, steroids, and alkylators. In addition,
      changes in Zfp459 and Fmo2 expression was reported in response after only
      treatment of antimetabolites. From these results, CDDO-Me is considered to have
      an immunosuppressive action and similar mechanism to antimetabolites. 

PMID- 25056778
TI  - Evaluation of hepatic damage by reactive metabolites--with consideration of
      circadian variation of murine hepatic glutathione levels.
AB  - Generally, reactive metabolites are detoxified by conjugation with glutathione
      (GSH). A GSH-depleted model was prepared by administering L-buthionine-(S,R)
      sulfoximine (BSO), which can be used to detect hepatic damage by reactive
      metabolites. However, BSO may cause adverse effects on other organs, such as
      renal damage by reactive metabolites because it depletes GSH in the whole body.
      The present study was designed to examine whether it was possible to specifically
      detect hepatic damage by reactive metabolites without reducing renal GSH levels
      by administering BSO in a time course when hepatic GSH levels are naturally
      reduced. Male BALB/c mice were administered reverse osmosis (RO) water or 20
      mmol/l BSO in drinking water for 4 days. Subsequently, animals in the RO water
      group were orally administered 500 mg/kg acetaminophen (APAP) at 9:00 or 15:00
      and in the BSO group at 9:00 for 4 days. As a result, severe hepatic damage and
      necrosis of the renal proximal tubules were observed in the BSO/APAP
      administration at 9:00 group, and all animals died on 1 or 2 days after APAP
      administration. Hepatic damage was clearly increased in the RO water/APAP
      administration at 15:00 group compared with the RO water/APAP administration at
      9:00 group. However, renal damage and deaths were not observed. This BSO
      administration model may detect renal damage induced by reactive metabolites.
      Using an administration time course, whereby hepatic GSH levels were naturally
      reduced, hepatic damage by reactive metabolites can be detected without secondary
      renal effects. 

PMID- 25056780
TI  - Comparing the role of silica particle size with mineral fiber geometry in the
      release of superoxide from rat alveolar macrophages.
AB  - Particulate air pollutants and mineral fibers activate inflammatory cells to
      release oxidants, which contribute to inflammation and injury in the lower
      respiratory tract. Our aim was to compare the role of silica particle size with
      mineral fiber length and width in the ability to induce superoxide release from
      rat alveolar macrophages. We estimated the ability of four types of silica
      particle samples, with different mode diameter, and three types of mineral fiber
      samples, with different geometric mean lengths and widths, to induce lucigenin
      dependent chemiluminescence (CL) from the cells per number of dust particles
      (i.e., silica particles and mineral fibers). A close positive correlation was
      observed between dust size and the ability to induce CL in silica as well as
      mineral fiber samples. Moreover, the ability of silica samples to induce CL was
      weaker than that of long mineral fiber sample. This ability increased at a larger
      rate in small silica particle and thin mineral fiber samples than in large silica
      particle and thick mineral fiber samples at the initial stage of administration.
      These results suggest that the kinetics of the induction superoxide release from
      macrophages is similar between silica particles and mineral fibers; moreover,
      this depends on silica particle size and mineral fiber geometry. Finally, large
      silica particles were more active than small ones. 

PMID- 25056773
TI  - Homogalacturonan-modifying enzymes: structure, expression, and roles in plants.
AB  - Understanding the changes affecting the plant cell wall is a key element in
      addressing its functional role in plant growth and in the response to stress.
      Pectins, which are the main constituents of the primary cell wall in dicot
      species, play a central role in the control of cellular adhesion and thereby of
      the rheological properties of the wall. This is likely to be a major determinant
      of plant growth. How the discrete changes in pectin structure are mediated is
      thus a key issue in our understanding of plant development and plant responses to
      changes in the environment. In particular, understanding the remodelling of
      homogalacturonan (HG), the most abundant pectic polymer, by specific enzymes is a
      current challenge in addressing its fundamental role. HG, a polymer that can be
      methylesterified or acetylated, can be modified by HGMEs (HG-modifying enzymes)
      which all belong to large multigenic families in all species sequenced to date.
      In particular, both the degrees of substitution (methylesterification and/or
      acetylation) and polymerization can be controlled by specific enzymes such as
      pectin methylesterases (PMEs), pectin acetylesterases (PAEs), polygalacturonases
      (PGs), or pectate lyases-like (PLLs). Major advances in the biochemical and
      functional characterization of these enzymes have been made over the last 10
      years. This review aims to provide a comprehensive, up to date summary of the
      recent data concerning the structure, regulation, and function of these
      fascinating enzymes in plant development and in response to biotic stresses.

PMID- 25056781
TI  - Neurobehavioral changes in response to alterations in gene expression profiles in
      the brains of mice exposed to low and high levels of mercury vapor during
      postnatal development.
AB  - This study examined the relationship between neurobehavioral changes and
      alterations in gene expression profiles in the brains of mice exposed to
      different levels of Hg(0) during postnatal development. Neonatal mice were
      repeatedly exposed to mercury vapor (Hg(0)) at a concentration of 0.057 mg/m(3)
      (low level), which was close to the current threshold value (TLV), and 0.197
      mg/m(3) (high level) for 24 hr until the 20(th) day postpartum. Behavioral
      responses were evaluated based on changes in locomotor activity in the open field
      test (OPF), learning ability in the passive avoidance response test (PA), and
      spatial learning ability in the Morris water maze (MM) at 12 weeks of age. No
      significant differences were observed in the three behavioral measurements
      between mice exposed to the low level of Hg(0) and control mice. On the other
      hand, total locomotive activity in mice exposed to the high level of Hg(0) was
      significantly decreased and central locomotion was reduced in the OPF task.
      Mercury concentrations were approximately 0.4 MUg/g and 1.9 MUg/g in the brains
      of mice exposed to the low and high levels of Hg(0), respectively. Genomic
      analysis revealed that the expression of 2 genes was up-regulated and 18 genes
      was down-regulated in the low-level exposure group, while the expression of 3
      genes was up-regulated and 70 genes was down-regulated in the high-level exposure
      group. Similar alterations in the expression of seven genes, six down-regulated
      genes and one up-regulated gene, were observed in both groups. The results
      indicate that an increase in the number of altered genes in the brain may be
      involved in the emergence of neurobehavioral effects, which may be associated
      with the concentration of mercury in the brain. Moreover, some of the commonly
      altered genes following exposure to both concentrations of Hg(0) with and without
      neurobehavioral effects may be candidates as sensitive biomarker genes for
      assessing behavioral effects in the early stages of development. 

PMID- 25056782
TI  - Effect of maternal exposure to carbon black nanoparticle during early gestation
      on the splenic phenotype of neonatal mouse.
AB  - Maternal exposure to environmental factors is implicated as a major factor in the
      development of the immune system in newborns. Newborns are more susceptible to
      microbial infection because their immune system is immature. Development of
      lymphocytes reflects an innate program of lymphocyte proliferation. The aim of
      this study was to investigate the effects of maternal exposure to carbon black
      nanoparticle (CB-NP) during early gestation on the development of lymphoid
      tissues in infantile mice. Pregnant ICR mice were treated with a suspension of CB
      NP (95 MUg kg(-1) time(-1)) by intranasal instillation on gestational day 5 and
      9. Spleen tissues were collected from offspring mice at 1, 3, 5, and 14 days
      postpartum. Splenocyte phenotypes were examined by investigating the pattern of
      surface molecules using flow cytometry. Gene expression in the spleen was
      examined by quantitative RT-PCR. CD3(+) (T), CD4(+) and CD8(+) cells were
      decreased in the spleen of 1-5-day-old offspring in the treated group. Expression
      level of Il15 was significantly increased in the spleen of newborn male
      offspring, and Ccr7 and Ccl19 were increased in the spleen of female offspring in
      the CB-NP group. Splenic mRNA change profiles by CBNP were similar between male
      and female offspring. This article concluded that exposure of pregnant mothers to
      CB-NP partially suppressed the development of the immune system of offspring
      mice. The decrease in splenic T cells in the treated group recovered at 14 days
      after birth. This is the first report of developmental effect of nanoparticle on
      the lymphatic phenotype. 

PMID- 25056783
TI  - Establishment of a novel experimental protocol for drug-induced seizure liability
      screening based on a locomotor activity assay in zebrafish.
AB  - As drug-induced seizures have severe impact on drug development, evaluating
      seizure induction potential of candidate drugs at the early stages of drug
      discovery is important. A novel assay system using zebrafish has attracted
      interest as a high throughput toxicological in vivo assay system, and we tried to
      establish an experimental method for drug-induced seizure liability on the basis
      of locomotor activity in zebrafish. We monitored locomotor activity at high-speed
      movement (> 20 mm/sec) for 60 min immediately after exposure, and assessed
      seizure liability potential in some drugs using locomotor activity. However this
      experimental procedure was not sufficient for predicting seizures because the
      potential of several drugs with demonstrated seizure potential in mammals was not
      detected. We, therefore, added other parameters for locomotor activity such as
      extending exposure time or conducting flashlight stimulation (10 Hz) which is a
      known seizure induction stimulus, and these additional parameters improved
      seizure potential detection in some drugs. The validation study using the
      improved methodology was used to assess 52 commercially available drugs, and the
      prediction rate was approximately 70%. The experimental protocol established in
      this present study is considered useful for seizure potential screening during
      early stages of drug discovery. 

PMID- 25056784
TI  - Effect of dihydropyrazines on human hepatoma HepG2 cells: a comparative study
      using 2,3-dihydro-5,6-dimethylpyrazine and 3-hydro-2,2,5,6-tetramethylpyrazine.
AB  - Dihydropyrazines (DHPs) are glycation products that are nonenzymatically
      generated in vivo and in food. In this study, we compared the effects of 2,3
      dihydro-5,6-dimethylpyrazine (DHP-1), a low toxicity DHP, and 3-hydro-2,2,5,6
      tetramethylpyrazine (DHP-3), a high toxicity DHP on the redox indices in HepG2
      cells. An apparent increase in intracellular hydrogen peroxide concentration was
      observed at 24 hr after 1 mM DHP-3 treatment. In addition, DHP-3 exposure
      significantly increased the mRNA levels of heme oxygenase-1 (HO-1) and glutamate
      cysteine ligase catalytic subunit (GCLC), which are stress-responsive genes, at 6
      hr (HO-1 and GCLC), 12 hr (HO-1 and GCLC) and 24 hr (GCLC) after exposure. These
      indices, with the exception of the increase in GCLC mRNA after a 6 hr exposure,
      were not affected by treatment with 1 mM DHP-1. HO-1, GCLC, and nuclear factor
      erythroid 2-related factor 2 (Nrf2) protein levels also increased at 6 hr (Nrf2),
      12 hr (Nrf2, HO-1 and GCLC) and 24 hr (GCLC) after DHP-3 treatment. The increase
      in HO-1 and Nrf2 protein levels were observed with lower concentration (0.5 mM)
      of DHP-3, and in agreement with this, antioxidant responsive element-luciferase
      reporter activity was significantly increased with exposure to at least 0.5 mM
      DHP-3. These results support our previous report establishing that oxidative
      stress is in part involved in the effects of DHP on mammalian cells.
      Additionally, our results suggest that the cell response to DHP-3 exposure was
      exerted via the activation of the Nrf2-ARE signal pathway. 

PMID- 25056785
TI  - Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress.
AB  - Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular
      carcinoma. The aim of the present work was to evaluate the impact of arecoline on
      human hepatic cytochrome P450 (CYP) enzymes in vitro and rat hepatic CYP enzymes,
      as well as the hepatic oxidative stress and liver injury of rats in vivo. The in
      vitro results indicated that arecoline hydrobromide (AH) has no significant
      effect on the activities of CYP2B, 2C9, 3A4, 1A2, 2E1 and 2D6 in human liver
      microsome (HLM). However, oral administration of AH at 4 and 20 mg/kg/d for seven
      consecutive days significantly increased the activities of rat hepatic CYP2B,
      2E1, 2D, 3A, 2C and 1A2. In addition, AH at 100 mg/kg/d significantly increased
      the levels of ALT, AST and MDA, decreased the levels of SOD, CAT, GSH-Px and GSH,
      in rat liver. The in vivo induction of AH on rat hepatic CYP isoforms suggested
      that the high risk of metabolic interaction should be existed when the substrate
      drugs of the six kinds of CYP isoforms was administered in betel-quid use human.
      Furthermore, the in vivo results also suggested that AH-induced hepatoxicity
      should be associated with the induction of AH on rat hepatic CYP2E1 and 2B. 

PMID- 25056786
TI  - Depigmentation of the skin induced by 4-(4-hydroxyphenyl)-2-butanol is
      spontaneously re-pigmented in brown and black guinea pigs.
AB  - Chemically induced depigmentation of the skin, which occurs following exposure
      (application or inhalation) to a depigmenting agent, is a disease with clinical
      findings similar to vitiligo. Recently, skin depigmentation possibly resulting
      from exposure to 4-(4-hydroxyphenyl)-2-butanol (HPB) was reported in humans.
      However, the role of HPB as the causative material of this skin depigmentation
      was not clear. To evaluate whether HPB has the potential for skin depigmentation,
      we characterized its effects on the skin of pigmented guinea pigs. Following
      exposure to 30% HPB 3 times/day for about 20 days, we found that obvious skin
      depigmentation was induced in brown and black guinea pigs. In the depigmented
      skin, there was a marked reduction in melanin pigment, and decreased numbers of
      DOPA and S-100 positive epidermal melanocytes were observed histologically. In
      addition, the depigmentation gradually recovered spontaneously and the number of
      melanocytes in the skin also increased after terminating the application of HPB.
      Complete re-pigmentation needed 31 to 70 days to return to the original baseline
      level. These data indicate that skin depigmentation is induced by the toxicity of
      HPB to epidermal melanocytes, and that the induced skin depigmentation can
      recover by terminating the application of HPB. 

PMID- 25056787
TI  - Mercury-induced amyloid-beta (Abeta) accumulation in the brain is mediated by
      disruption of Abeta transport.
AB  - According to a recent study, mercury (Hg) exposure contributes to Alzheimer's
      disease (AD). However, the underlying mechanisms are not understood. This study
      investigated the effect of methylmercury (MeHg) treatment on the generation,
      degradation, and transport of amyloid beta-protein (Abeta) in the brain. Wistar
      rats were administered MeHg by gavage (0, 20, 200, and 2,000 MUg Hg/kg/day) for 4
      weeks. The total Hg in the blood and brain regions was measured, and the levels
      of Abeta42 in plasma, cerebrospinal fluid (CSF), and brain regions were
      estimated. The expression of amyloid precursor protein (APP), beta-site APP
      cleaving enzyme 1 (BACE1), and neprilysin (NEP) in the brain regions was
      determined, in addition to the expression of low-density lipoprotein receptor
      related protein 1 (LRP1) and the receptor for advanced glycation end products
      (RAGE) in the brain capillary endothelium (BCE). Finally, the amount of soluble
      low-density lipoprotein receptor-related protein (sLRP) in the plasma was
      determined. Abeta42 levels were decreased in the CSF of the 2,000 MUg Hg/kg/day
      group compared with controls, and Abeta42 levels increased in the hippocampus
      (HC) in a dose-dependent manner. MeHg decreased LRP1 expression but increased
      RAGE levels in BCE. sLRP levels were decreased in the plasma of the MeHg-treated
      rats. They were positively correlated with CSF Abeta42 and negatively correlated
      with Abeta42 and Hg levels in HC. These results imply that MeHg reduces the
      transportation of Abeta, thereby resulting in the accumulation of the protein in
      the HC. Plasma sLRP levels may be an early biomarker of Hg-induced Abeta
      accumulation in the brain.

PMID- 25056788
TI  - Indoxyl sulfate induces renin release and apoptosis of kidney mesangial cells.
AB  - BACKGROUND: Indoxyl sulfate is considered to play a pathological role in the
      progression of chronic kidney disease. The aim of this study was to investigate
      the deleterious effects of indoxyl sulfate on kidney mesangial cells. MATERIALS
      AND METHODS: Rat renal mesangial cells were exposed to indoxyl sulfate at a
      serial concentrations. Cytotoxicity of indoxyl sulfate on renal mesangial cells
      was determined using MTT assay. Protein levels of cleaved caspase-3, angiotensin,
      angiotensin converting enzyme (ACE) and renin were detected by immunoblotting.
      Reverse transcriptional PCR was performed to determine the mRNA expression.
      RESULTS: Level of cleaved caspase-3 was augmented while the cell viability was
      inhibited by indoxyl sulfate in a dose-dependent manner. The mRNA expressions of
      pro-renin and ACE were upregulated in mesangial cells exposed to indoxyl sulfate.
      Level of renin and ACE was increased in response to indoxyl sulfate exposure in
      time-dependent fashion. CONCLUSION: Indoxyl sulfate increased viability and
      induced cell death of renal mesangial cells, which is time-dependent. The loss of
      cell viability is attributed to caspase-3 activity through apoptosis pathway. RAS
      in renal mesangial cells is activated in response to indoxyl sulfate treatment.

PMID- 25056789
TI  - How does airway exposure of aflatoxin B1 affect serum albumin adduct
      concentrations? Evidence based on epidemiological study and animal
      experimentation.
AB  - Aflatoxin B1 (AFB1) airway inhalation represents an additional route of exposure
      to this toxin. However, the association between AFB1 inhalation and serum AFB1
      albumin adducts remains unclear. The aim of this study was to explore the
      association between airway exposure to AFB1 and serum AFB1 albumin adduct
      concentrations via an epidemiological study, as well as in an AFB1 airway
      exposure animal model. Our epidemiological study was conducted in a sugar factory
      in the Guangxi Autonomous Region of China. In order to examine fungal
      contamination, air samples were obtained in the workshop and areas outside the
      workshop, such as the office and nearby store. Dust samples were also collected
      from the bagasse warehouse and presser workshop, and were analyzed using an
      indirect competitive enzyme-linked immunosorbent assay (ELISA). Additionally,
      blood samples were collected from a total of 121 workshop workers, and a control
      group (n = 80) was comprised of workers who undertook administrative tasks or
      other work outside the workshop. The animal experiment was conducted in the
      laboratory animal center of Guangxi Medical University, where a total of 60 adult
      male rabbits were involved in this study. By intubation, AFB1 was administered in
      three groups of rabbits daily, at dose rates of 0.075, 0.05 and 0.025 mg/kg/day
      for a period of 7 days. Blood samples were collected on day 1, day 3, day 7 and
      day 21, and the measurements of the AFB1 albumin adducts in the serum were
      performed by a double antibody sandwich ELISA. The epidemiological study showed
      that serum albumin adducts were detected in 67 workshop workers (55.37%), and the
      values ranged 6.4 pg/mg albumin to 212 pg/mg albumin (mean value: 51 +/- 4.62
      pg/mg albumin). In contrast, serum albumin adducts were detected in only 7
      control group participants, with the values ranging from 9 pg AFB1/mg albumin to
      59 pg/mg albumin (mean value: 20 +/- 13.72 pg/mg albumin). The animal experiment
      revealed that the rabbits had detectable levels of AFB1 in their serum with a
      minimum effective dose of 0.05 mg/kg/day; while 11 of 17 (64.71%) rabbits had
      detectable levels of AFB1 albumin adducts in the high exposure group (0.075
      mg/kg/day), and only 5 rabbits (26.32%) had detectable levels of AFB1 albumin
      adducts in the moderate exposure group (0.05 mg/kg/day). No rabbits had
      detectable levels of AFB1 albumin adducts in the low exposure group (0.025
      mg/kg/day). Our results demonstrated that only exposure to a certain level of
      AFB1 would result in detectable levels of serum AFB1 albumin adducts.
      Interventional programs aimed at reducing exposure to AFB1 by inhalation are
      urgently needed in high-risk populations. Additional large-sample, well-designed
      randomized controlled trials are needed to further confirm our results. 

PMID- 25056790
TI  - Establishment of an in silico phototoxicity prediction method by combining
      descriptors related to photo-absorption and photo-reaction.
AB  - One of the mechanisms of phototoxicity is photo-reaction, such as reactive oxygen
      species (ROS) generation following photo-absorption. We focused on ROS generation
      and photo-absorption as key-steps, because these key-steps are able to be
      described by photochemical properties, and these properties are dependent on
      chemical structure. Photo-reactivity of a compound is described by HOMO-LUMO Gap
      (HLG), generally. Herein, we showed that HLG can be used as a descriptor of the
      generation of reactive oxygen species. Moreover, the maximum-conjugated pi
      electron number (PENMC), which we found as a descriptor of photo-absorption,
      could also predict in vitro phototoxicity. Each descriptor could predict in vitro
      phototoxicity with 70.0% concordance, but there was un-predicted area found (gray
      zone). Interestingly, some compounds in each gray zone were not common,
      indicating that the combination of two descriptors could improve prediction
      potential. We reset the cut-off lines to define positive zone, negative zone and
      gray zone for each descriptor. Thereby we overlapped HLG and PENMC in a graph,
      and divided the total area to nine zones with cut-off lines of each descriptor.
      The rules to prediction were decided to achieve the best concordance, and the
      concordances were improved up to 82.8% for self-validation, 81.6% for cross
      validation. We found common properties among false positive or negative
      compounds, photo-reactive structure and photo-allergenic, respectively. In
      addition, our method could be adapted to compounds rich in structural diversity
      using only chemical structure without any statistical analysis and complicated
      calculation.

PMID- 25056791
TI  - Effects of postnatal dexamethasone treatment on mRNA expression profiles of genes
      related to alveolar development in an emphysema model in mice.
AB  - Emphysema can be induced in animals by postnatal treatment with dexamethasone
      (Dex) and such models have been widely used for various research. However, it is
      not clear what are the effects of Dex on assembly of alveolar elastic fibers in
      the emphysema model in mice. This study compared the expression profile of genes
      related to alveolar development between Dex treated and control mice during the
      treatment from postnatal day 3 (P3) to P14 with a 2-day break. From morphological
      observation of lung sections on P42, we confirmed the induction of emphysema in
      the treated mice. The mRNA expression level of fibrillin-1, which consists of
      microfibrils as a scaffold to form elastic fibers, and fibulin-5, which is a key
      protein reinforcing the fibers, reached maximum on P7 in control mice. However,
      in the Dex group, expression levels both types of mRNA were much lower with no
      clear expression peak. On the other hand, mRNA expression of tropoelastin, the
      main component in elastic fibers, reached maximum on P5 in the Dex group, which
      was 9 days earlier than in the control group. At this time, the amount of
      microfibrils might not be enough for tropoelastin to be deposited completely in
      Dex treated mice. This imbalance in the expression of tropoelastin and
      microfibril might interfere with the efficient formation of elastic fibers. 

PMID- 25056792
TI  - Microarray analysis of differentially expressed gene responses to bisphenol A in
      Arabidopsis.
AB  - Environmental levels of bisphenol A (BPA) are a global concern because the
      compound can cause damage to reproductive organs, the thyroid gland, and brain
      tissues at developmental stages. Plants are important in removing BPA from the
      atmosphere, soil, and water. However, knowledge on the mechanism by which plants
      respond to this compound is limited. To determine the response mechanism of
      plants to BPA, we used a microarray system to analyze the gene expression
      patterns of Arabidopsis thaliana after irrigation with 3.0 mM BPA. We identified
      651 genes that were differentially expressed upregulated and 470 genes that were
      downregulated by BPA. These genes may specifically contribute to BPA uptake,
      transformation, conjugation, and compartmentation in plants. The potential
      function of upregulated genes in plant defense against BPA was also determined. 

PMID- 25056793
TI  - Are phosphate dusts able to trigger systemic inflammatory reaction and elevate
      inflammatory markers?

PMID- 25056794
TI  - Response to letter to the editor.

PMID- 25056796
TI  - Myogenin gene expression is not altered in the developing diaphragm of nitrofen
      induced congenital diaphragmatic hernia.
AB  - PURPOSE: Pleuroperitoneal folds (PPFs) represent the only source of muscle
      precursors cells (MPCs) in the primordial diaphragm. However, the exact
      pathogenesis of malformed PPFs and congenital diaphragmatic hernia (CDH) remains
      unclear. The muscle-specific transcription factor myogenin plays a key role
      during development and muscularization of the fetal diaphragm. Although myogenin
      knockout mice lack skeletal muscle fibers, the diaphragmatic musculature is
      intact without any defects. It has further been demonstrated that proliferation
      and differentiation of MPCs in PPFs and developing diaphragms are normal in
      rodent CDH models. We hypothesized that myogenin gene expression is not altered
      in malformed PPFs, developing diaphragms and diaphragmatic musculature in the
      nitrofen-induced CDH model. METHODS: Pregnant rats were exposed to nitrofen or
      vehicle on gestational day 9 (D9). Fetuses were harvested during PPF formation
      (D13), diaphragmatic development (D14-15) and muscularization (D18-21). Fetal
      PPFs, developing diaphragms and diaphragmatic musculature were dissected and
      divided into nitrofen and control groups. Myogenin mRNA levels were analyzed by
      quantitative real-time polymerase chain reaction, while immunohistochemistry was
      performed to investigate myogenin protein expression and distribution. RESULTS:
      Relative mRNA expression of myogenin was not significant different in PPFs (0.30
      +/- 0.09 vs. 0.48 +/- 0.09; P = 0.37), developing diaphragms (1.25 +/- 0.29 vs.
      1.60 +/- 0.32; P=0.53) and diaphragmatic musculature (1.08 +/- 0.24 vs. 1.59 +/-
      0.20; P = 0.15) of nitrofen-exposed fetuses compared to controls. Myogenin
      immunoreactivity was not altered in the muscular components of malformed PPFs,
      developing diaphragms and diaphragmatic musculature of nitrofen-exposed fetuses
      compared to controls. CONCLUSION: Myogenin gene expression is not altered in
      PPFs, developing diaphragms and diaphragmatic musculature in the nitrofen-induced
      CDH model, thus suggesting that diaphragmatic defects in this model develop
      independent of myogenic processes.

PMID- 25056797
TI  - The diagnosis of fetal esophageal atresia and its implications on perinatal
      outcome.
AB  - The current diagnostic accuracy and perinatal outcome of fetuses with esophageal
      atresia (EA) continues to be debated. In this review, we report on our experience
      at a tertiary care fetal center with the prenatal ultrasound diagnosis of EA.
      Enrollment criteria included a small/absent stomach bubble with a normal or
      elevated amniotic fluid index between 2005 and 2013. Perinatal outcomes were
      analyzed and compared to postnatally diagnosed EA cases. Of the 22 fetuses
      evaluated, polyhydramnios occurred in 73%. Three (14%) died in utero or shortly
      after birth, but none had EA. In the presence of an absent/small stomach and
      polyhydramnios, the positive predictive value for EA was 67%. In fetal EA cases
      confirmed postnatally (group 1, n = 11), there were no differences in gestational
      age, birthweight, or mortality when compared to postnatally diagnosed infants
      (group 2, n = 59). Group 1 was associated with long-gap EA, need for esophageal
      replacement, and increased hospital length of stay. When taken in context with
      the current literature, we conclude that ultrasound findings suggestive of EA
      continue to be associated with a relatively high rate of false positives.
      However, among postnatally confirmed cases, there is an increased risk for long
      gap EA and prolonged hospitalization.

PMID- 25056798
TI  - Changes in polychlorinated biphenyl (PCB) exposure in tree swallows (Tachycineta
      bicolor) nesting along the Sheboygan River, WI, USA.
AB  - Exposure to polychlorinated biphenyls (PCBs) in tree swallow (Tachycineta
      bicolor) eggs on the Sheboygan River, Wisconsin in the 1990s was higher at sites
      downstream (geometric means = 3.33-8.69 MUg/g wet wt.) of the putative PCB source
      in Sheboygan Falls, Wisconsin than it was above the source (1.24 MUg/g) with the
      exposure declining as the distance downstream of the source increased. A similar
      pattern of declining exposure was present in the 2010s as well. Although exposure
      to PCBs in eggs along the Sheboygan River at sites downstream of Sheboygan Falls
      has declined by ~60 % since the mid-1990s (8.69 down to 3.27 MUg/g) there still
      seems to be residual pockets of contamination that are exposing some individuals
      (~25 %) to PCB contamination, similar to exposure found in the 1990s. The
      exposure patterns in eggs and nestlings among sites, and the changes between the
      two decades, are further validated by accumulation rate information.

PMID- 25056800
TI  - Metalation of polyamine dendrimers with ethynylcobalticenium for the construction
      of mono- and heterobimetallic polycationic metallodendrimers.
AB  - The introduction of robust redox groups at the periphery of common amine
      terminated dendrimers is of interest in the design of dendritic nanobatteries,
      sensors, and redox catalysts. Here we are applying the recently discovered
      uncatalyzed hydroamination of ethynylcobalticenium, a mild "green" reaction that
      quantitatively yields trans-enamines without the formation of any byproduct, to
      functionalize dendrimers that are terminated with primary or secondary amino
      groups. Poly(amido amine) (PAMAM) dendrimers terminated by primary amino groups
      and arene-centered dendrimers terminated by secondary amino groups yield
      dendrimers that contain up to 81 trans-enamine-cobalticenium termini using this
      reaction. The hydroamination reaction was also conducted with dendrimers that
      contained ferrocenylmethylamino groups, which yielded dendrimers that contained
      both ferrocenyl and cobalticenium termini. The size of the dendrimers was
      investigated using both dynamic light scattering and diffusion-ordered
      spectroscopy (DOSY) (1)H NMR spectroscopy, and the number of electrons involved
      in heterogeneous multielectron transfers at electrodes was searched by cyclic
      voltammetry. The latter works well up to the 27-branch dendrimer, whereas the 81
      dendrimer yielded a result in an excess amount (110 electrons) owing to
      adsorption onto the cathode that becomes all the more significant as the
      metallodendrimer size increases.

PMID- 25056799
TI  - Role of bone mineral density in predicting morphometric vertebral fractures in
      patients with HIV infection.
AB  - This study investigated the bone of HIV patients both in terms of quantity and
      quality. It was found that HIV-infected patients did fracture independently of
      the degree of bone demineralization as in other forms of secondary osteoporosis.
      INTRODUCTION: We aimed to determine the prevalence of vertebral fractures (VFs)
      in HIV patients who were screened by bone mineral density (BMD) and to explore
      possible factors associated with VFs. METHODS: This is a cross-sectional study
      that included HIV-infected patients recruited in the Clinic of Infectious and
      Tropical Diseases and that underwent BMD measurement by dual-energy X-ray
      absorptiometry (DXA) at the lumbar spine and hip (Lunar Prodigy, GE Healthcare).
      For the assessment of VFs, anteroposterior and lateral X-ray examinations of the
      thoracic and lumbar spines were performed and were centrally digitized. Logistic
      regression models were used in the statistical analysis of factors associated
      with VFs. RESULTS: One hundred thirty-one consecutive patients with HIV infection
      (93 M, 38 F, median age 51 years; range, 36-75) underwent BMD measurement: 25.2 %
      of patients showed normal BMD, while 45 % were osteopenic and 29.7 %
      osteoporotic. Prevalence of low BMD (osteopenia and osteoporosis) was higher in
      females as compared to males (90 vs 69 %) with no significant correlation with
      age and body mass index. VFs occurred more frequently in patients with low BMD as
      compared to patients with normal BMD (88.5 vs. 11.4 %; p < 0.001) without any
      significant difference between osteopenia and osteoporosis (43 vs. 46 %; p =
      0.073). VFs were significantly associated with older age and previous AIDS
      events. CONCLUSIONS: These results suggest a BMD <-1 threshold to identify
      patients at risk of skeletal fragility and, therefore, good candidates for
      morphometric evaluation of spine X-ray in line with other forms of secondary
      osteoporosis with impaired bone quality.

PMID- 25056801
TI  - Preventable and potentially preventable serious adverse reactions induced by oral
      protein kinase inhibitors through a database of adverse drug reaction reports.
AB  - Antineoplastic drugs are one of the pharmacological classes more frequently
      involved in occurrence of "serious" adverse drug reactions. However, few
      epidemiological data are available regarding the preventability of adverse drug
      reactions with ambulatory cancer chemotherapy. We assessed the rate and
      characteristics of "preventable" or "potentially preventable" "serious" adverse
      drug reactions induced by oral protein kinase inhibitors (PKIs). We performed a
      retrospective study with all "serious" adverse drug reactions (ADRs) recorded
      from 1 January 2008 to 31 December 2009 in the French Pharmacovigilance Database
      with the eight oral protein kinase inhibitors marketed in France: sorafenib,
      imatinib, erlotinib, sunitinib, dasatinib, lapatinib, nilotinib and everolimus
      (Afinitor(r)) using the French adverse drug reactions preventability scale. This
      study was carried out on 265 spontaneous notifications. Most of adverse drug
      reactions were "unpreventable" (63.8 %). Around one third were "unevaluable" due
      to notifications poorly documented (medical history, dosage, use of drugs as
      first or second intention, concomitant drugs). One (0.4 %) adverse drug reaction
      was "preventable" with dasatinib (subdural hematoma) and three (1.1 %) were
      "potentially preventable" (hepatic adverse drug reactions): two with imatinib and
      one with sorafenib. For these four cases, we identified some characteristics:
      incorrect dosages, drug interactions and off-label uses. An appropriate
      prescription could avoid the occurrence of 1.5 % "serious" adverse drug reactions
      with oral PKIs. This rate is low and further studies are needed to compare our
      results by using other preventability instruments and to improve the French ADRs
      Preventability Scale. 

PMID- 25056804
TI  - MALDI imaging mass spectrometry: discrimination of pathophysiological regions in
      traumatized skeletal muscle by characteristic peptide signatures.
AB  - Due to formation of fibrosis and the loss of contractile muscle tissue, severe
      muscle injuries often result in insufficient healing marked by a significant
      reduction of muscle force and motor activity. Our previous studies demonstrated
      that the local transplantation of mesenchymal stromal cells into an injured
      skeletal muscle of the rat improves the functional outcome of the healing
      process. Since, due to the lack of sufficient markers, the accurate
      discrimination of pathophysiological regions in injured skeletal muscle is
      inadequate, underlying mechanisms of the beneficial effects of mesenchymal
      stromal cell transplantation on primary trauma and trauma adjacent muscle area
      remain elusive. For discrimination of these pathophysiological regions, formalin
      fixed injured skeletal muscle tissue was analyzed by MALDI imaging MS. By using
      two computational evaluation strategies, a supervised approach (ClinProTools) and
      unsupervised segmentation (SCiLS Lab), characteristic m/z species could be
      assigned to primary trauma and trauma adjacent muscle regions. Using "bottom-up"
      MS for protein identification and validation of results by immunohistochemistry,
      we could identify two proteins, skeletal muscle alpha actin and carbonic
      anhydrase III, which discriminate between the secondary damage on adjacent tissue
      and the primary traumatized muscle area. Our results underscore the high
      potential of MALDI imaging MS to describe the spatial characteristics of
      pathophysiological changes in muscle. 

PMID- 25056805
TI  - Adolescent language brokering in diverse contexts: associations with parenting
      and parent-youth relationships in a new immigrant destination area.
AB  - In the US, children in immigrant families have a longstanding history of language
      brokering for their parents. Scholars have surmised that youth's role in language
      brokering may influence the nature of parenting practices and parent-child
      relationships that are important to the positive adjustment of adolescent youth.
      Research findings in this regard, however, have been mixed. Drawing from the
      family stress model and the concept of adolescent helpfulness, the present study
      examined how language brokering across different contexts-school, community, and
      home-was associated with indicators of parental support and parental behavioral
      control. The sample included 118 (53% female) primarily Mexican- and Central
      American-origin 7th, 9th, and 11th grade children in Latino immigrant families
      living in suburban Atlanta, an important new immigrant destination. The results
      from structural equation models indicated that language brokering at home
      translations for items such as bills, credit card statements, and insurance forms
      was associated with less parental decision-making authority, lower levels of
      parental knowledge, and less parent-child closeness. Language brokering pertinent
      to school and community contexts, on the other hand, was not associated with
      variations in parenting. The adverse consequences for parenting conferred by
      youth translating insurance forms and family financial bills may stem from the
      excessive cognitive demands placed on youth in these situations, as well as the
      elevated power that youth gain in relationship to their immigrant parents. For
      the country's rapidly growing population of youth being raised by immigrant
      Latino parents, it is important to consider that youth's role as language broker
      at home may affect closeness in the parent-child relationship as well as the
      degree to which parents are able to maintain authority over youth's behaviors.

PMID- 25056803
TI  - Microglia as a critical player in both developmental and late-life CNS
      pathologies.
AB  - Microglia, the tissue-resident macrophages of the brain, are attracting
      increasing attention as key players in brain homeostasis from development through
      aging. Recent works have highlighted new and unexpected roles for these once
      enigmatic cells in both healthy central nervous system function and in diverse
      pathologies long thought to be primarily the result of neuronal malfunction. In
      this review, we have chosen to focus on Rett syndrome, which features early
      neurodevelopmental pathology, and Alzheimer's disease, a disorder associated
      predominantly with aging. Interestingly, receptor-mediated microglial
      phagocytosis has emerged as a key function in both developmental and late-life
      brain pathologies. In a mouse model of Rett syndrome, bone marrow transplant and
      CNS engraftment of microglia-like cells were associated with surprising
      improvements in pathology-these benefits were abrogated by block of phagocytic
      function. In Alzheimer's disease, large-scale genome-wide association studies
      have been brought to bear as a method of identifying previously unknown
      susceptibility genes, which highlight microglial receptors as promising novel
      targets for therapeutic modulation. Multi-photon in vivo microscopy has provided
      a method of directly visualizing the effects of manipulation of these target
      genes. Here, we review the latest findings and concepts emerging from the rapidly
      growing body of literature exemplified for Rett syndrome and late-onset, sporadic
      Alzheimer's disease. 

PMID- 25056806
TI  - Forestry impacts on the hidden fungal biodiversity associated with bryophytes.
AB  - Recent studies have revealed an unexpectedly high, cryptic diversity of fungi
      associated with boreal forest bryophytes. Forestry practices heavily influence
      the boreal forest and fundamentally transform the landscape. However, little is
      known about how bryophyte-associated fungal communities are affected by these
      large-scale habitat transformations. This study assesses to what degree bryophyte
      associated fungal communities are structured across the forest successional
      stages created by current forestry practices. Shoots of Hylocomium splendens were
      collected in Picea abies dominated forests of different ages, and their
      associated fungal communities were surveyed by pyrosequencing of ITS2 amplicons.
      Although community richness, diversity and evenness were relatively stable across
      the forest types and all were consistently dominated by ascomycete taxa, there
      was a marked shift in fungal community composition between young and old forests.
      Numerous fungal operational taxonomic units (OTUs) showed distinct affinities for
      different forest ages. Spatial structure was also detected among the sites,
      suggesting that environmental gradients resulting from the topography of the
      study area and dispersal limitations may also significantly affect bryophyte
      associated fungal community structure. This study confirms that Hylocomium
      splendens hosts an immense diversity of fungi and demonstrates that this
      community is structured in part by forest age, and as such is highly influenced
      by modern forestry practices. 

PMID- 25056807
TI  - Early mother-child attachment and behavior problems in middle childhood: the role
      of the subsequent caregiving environment.
AB  - The current study investigated associations between early mother-child
      attachment, as well as mother-child and teacher-child relationships, and
      internalizing and externalizing behaviors in middle childhood. Data from the
      NICHD Study of Early Child Care and Youth Development were used. Findings from a
      series of individual growth curve analyses revealed that attachment security was
      negatively related to internalizing and externalizing behaviors, while
      insecure/other and avoidant attachment were positively related to internalizing
      behaviors. In addition, longitudinal associations were found between mother-child
      and teacher-child relationships and internalizing and externalizing behaviors
      across middle childhood. Implications for attachment theory are discussed. 

PMID- 25056808
TI  - A comparison of different oral therapies versus no treatment for erectile
      dysfunction in 196 radical nerve-sparing radical prostatectomy patients.
AB  - We retrospectively analyzed the effects on the erectile function (EF) of no
      treatment (NT), and an oral therapy (OT; on-demand therapy (OD) or a regimented
      rehabilitation (RR) program with phosphodiesterase type 5 inhibitors (PDE5-Is)),
      in a cohort of 196 consecutive patients following nerve-sparing radical
      retropubic prostatectomy (NSRRP). Patients undergoing bilateral NSRRP (BP; n =
      147) and unilateral NSRRP (UP; n = 49), chose between OT (PDE5-Is OD or RR
      program) and NT. Patients who chose OD therapy received PDE5-Is (100 mg
      sildenafil, 20 mg tadalafil and vardenafil), whereas patients who chose the RR
      program received 100 mg sildenafil or 20 mg vardenafil three times a week, or 20
      mg tadalafil twice a week at bedtime. The t-test for unpaired data and Fisher
      test were used for univariate analyses, logistic regression multivariate analysis
      was used to test the accuracy of available variables to predict EF recovery after
      radical prostatectomy. Potency rates were significantly correlated with the
      surgical technique and with OT when compared to NT (P < 0.02), respectively 68.7%
      for BP (61% with no therapy and 71% with PDE5-Is) and 44% for UP (29% with no
      therapy and 51% with PDE5-Is), while no statistically significative differences
      were found between OD and rehabilitation protocols (72% with rehabilitation and
      70% with OD therapy in BP, 52% with rehabilitation and 50% with OD therapy in UP;
      P = NS). Early OT with PDE5-Is (OD or RR program) was superior to NT in recovery
      of EF in NSRRP. Furthermore, an RR program with PDE5-Is did not appear to be
      superior to OD therapy.

PMID- 25056809
TI  - Pharmacokinetics and drying time of testosterone 2% gel in men with hypogonadism:
      a multicenter, open-label, single-arm trial.
AB  - The objective of this study was to assess drying time after application of
      testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals), time needed for serum
      total testosterone (TT) to reach the eugonadal range (? 300 ng dl(-1)), and time
      to steady-state serum TT. Thirty-four men with primary or secondary hypogonadism
      were enrolled in the study; 31 men were included in the pharmacokinetics (PKs)
      population. Testosterone 2% gel (40 mg) was applied once daily in the morning to
      the front and inner thighs for 14 days. Median gel drying time was 2.4 min (95%
      confidence interval (CI), 1.7-3.4 min; n = 31). Serum TT concentrations reached
      the target eugonadal range with a median time of 2.9 h (95% CI, 1.9-4.3 h; n =
      24). Median time to steady-state serum TT concentration was 1.1 days (95% CI, 0.7
      3.4 days; n = 31). Six patients (17.6%; n = 34) reported treatment-related
      adverse events; all were mild. The results from this 14-day PK study in men with
      hypogonadism suggest that testosterone 2% gel dries, on average, in <3 min after
      application and that testosterone 2% gel rapidly reaches the target eugonadal
      range and attains steady-state serum TT concentrations in about 1 day.

PMID- 25056810
TI  - Expression and distribution of the transient receptor potential cationic channel
      ankyrin 1 (TRPA1) in the human vagina.
AB  - The transient receptor potential cationic channel type A1 (TRPA1), belonging to a
      superfamily of cationic membrane channels, has been suggested to act as mechano-
      and pain sensor and, thus, to play a role in neurotransmission in the human body,
      including the urogenital tract. While the expression of TRPA1 has been
      investigated in a variety of tissues, up until today, no study has addressed the
      expression and distribution in the female genital tract. The present study aimed
      to investigate the expression and distribution of TRPA1 protein in human vaginal
      tissue. Reverse transcriptase PCR (RT-PCR) was applied in order to identify
      messenger ribonuleic acid specifically encoding for TRPA/A1. The distribution of
      TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling
      peptide calcitonin gene-related peptide (CGRP) was examined by means of
      immunohistochemical methods (double-antibody technique, laser fluorescence
      microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences
      specific for TRPA in the vaginal wall and epithelium. Immunostaining related to
      TRPA1 was observed in the basal epithelium and in slender varicose nerve fibers
      transversing the subepithelial and stromal space of the vaginal sections. In
      addition, these fibers presented immunoreactivity specific for nNOS or CGRP. The
      smooth musculature of the vaginal wall and small vessels interspersing the tissue
      did not present signals related to TRPA1. The findings indicate that TRPA1 might
      be involved in afferent neurotransmission in the vagina and work synergistically
      together with the nitric oxide/cyclic guanosine monophosphate pathway. 

PMID- 25056811
TI  - Succinate production from CO2-grown microalgal biomass as carbon source using
      engineered Corynebacterium glutamicum through consolidated bioprocessing.
AB  - The potential for production of chemicals from microalgal biomass has been
      considered as an alternative route for CO2 mitigation and establishment of
      biorefineries. This study presents the development of consolidated bioprocessing
      for succinate production from microalgal biomass using engineered Corynebacterium
      glutamicum. Starch-degrading and succinate-producing C. glutamicum strains
      produced succinate (0.16 g succinate/g total carbon source) from a mixture of
      starch and glucose as a model microalgal biomass. Subsequently, the engineered C.
      glutamicum strains were able to produce succinate (0.28 g succinate/g of total
      sugars including starch) from pretreated microalgal biomass of CO2-grown
      Chlamydomonas reinhardtii. For the first time, this work shows succinate
      production from CO2 via sequential fermentations of CO2-grown microalgae and
      engineered C. glutamicum. Therefore, consolidated bioprocessing based on
      microalgal biomass could be useful to promote variety of biorefineries.

PMID- 25056812
TI  - Phthalate esters in water and sediments of the Kaveri River, India: environmental
      levels and ecotoxicological evaluations.
AB  - Phthalate esters are well known for their environmental contamination and
      toxicological effects as "endocrine disruptors." In this study, environmental
      levels of phthalate esters and ecotoxicological risk assessments were performed
      in one of the major rivers in India, the Kaveri. Water and sediment samples were
      collected during 2010-2012 representing the major stretch of the river and
      extracted by solid-phase and ultrasonic methods, respectively, and analyzed for
      six major phthalates by using a gas chromatograph-mass spectrometer. The
      analytical recovery for phthalates in water and sediment ranged from 79 to 121%.
      Results indicated that diethyl phthalate (DEP) and dimethyl phthalate were found
      in every sample, whereas butylbenzyl phthalate and diethylhexyl phthalate (DEHP)
      were detected in 92% of the water samples. Likewise, in sediment samples, DEP was
      found most often (94%). The total phthalates in water samples ranged from 313 to
      1,640 ng/l, whereas in sediments it was 2 to 1,438 ng/g dw (dry weight) with DEHP
      having the highest concentration. Human health risk assessment based on drinking
      water consumption showed no potential risk for phthalates and also DEHP levels
      were safe with respect to USEPA guideline (6,000 ng/l). Further, DEHP and di-n
      octyl phthalate levels in water were expected to pose little threat to sensitive
      organisms in the riverine ecosystem as per ECOSAR chronic values. In case of
      sediment, the DEHP concentration was well above the USEPA sediment guideline
      value. To our knowledge, this is the first study to describe the levels and
      ecotoxicological risks of phthalates in Kaveri River, India.

PMID- 25056813
TI  - Peer support for patients with type 2 diabetes in rural communities of China:
      protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: The prevalence of diabetes has been growing rapidly in developing
      countries. This causes devastating economic burdens and increases demands on the
      health care system. Therefore, there is an urgent need to find a cost-effective
      and multi-faceted approach for diabetes care. Peer support models provide a
      potentially low-cost, flexible means which complements the current existing
      health care services. In this way, trained peer leaders can become qualified
      extensions to a formal healthcare system, capable of assisting education delivery
      and bolstering the efforts of professional staff. As such, creating a cultural
      specific peer support program and determining whether it is acceptable and cost
      effective in rural communities of China is crucial. This study aims to implement
      and evaluate biophysical and psychosocial outcomes of peer support program for
      people with type 2 diabetes in rural communities, and to explore the program's
      feasibility and sustainability in China. METHODS/DESIGN: This study is a cluster
      randomised controlled trial. All consenting patients will be randomised by
      community staff members to receive either peer support or the control care. The
      data collection and analysis including social demographics, health status,
      psychosocial status, economic status and biomedical measures will be collected at
      baseline, 6 months, and 12 months. The primary indicator measured is the change
      in HbA1c, whereas secondary indicators include biophysical, psychosocial
      functioning and other lifestyle factors. Finally, economic evaluations will
      determine whether the program is cost effective. DISCUSSION: This protocol is a
      cluster randomized, controlled trial of group-based peer support for people with
      type 2 diabetes in the community settings of rural China. Results from this trial
      may provide evidence to the effectiveness of peer support; furthermore, they will
      provide valuable information concerning the acceptability and feasibility of a
      new approach to improve diabetes self-management among resource-constrained
      settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02119572, April
      18, 2014.

PMID- 25056815
TI  - The independent relations of both residential self-selection and the environment
      to physical activity.
AB  - Residential self-selection is supposed to bias the relation between residential
      environments and physical activity, but empirical analyses are still rare. This
      study examines the association while simultaneously considering the effect of
      residential self-selection criteria. One thousand two hundred and forty-five
      German students were asked to report their physical activity, their perceived
      environment, and their reasons for choosing their neighbourhood. Structural
      equation modelling was employed. Reasons for choosing a neighbourhood were
      related to actual environmental characteristics. Utilitarian reasons were related
      to less physical activity, hedonic reasons were related to higher physical
      activity. The street network was related to higher physical activity independent
      of residential self-selection. Our results support the weight of both individual
      preferences and the street network on physical activity. The residential
      environment has an impact on people's amount of physical activity regardless of
      their reasons for choosing a neighbourhood and should therefore be considered a
      resource in health prevention and promotion. 

PMID- 25056814
TI  - Genetic variation of TBX21 gene increases risk of asthma and its severity in
      Indian children.
AB  - T-box transcription factor protein (TBX21) is encoded by the TBX21 gene in human.
      It is crucial for naive T lymphocyte development, interferon-gamma production,
      airway hyperresponsiveness and regulation of corticosteroid response in
      asthmatics. Polymorphisms rs4794067 and rs16947078 of TBX21 were found to be
      associated with acetylsalicylic acid-induced and allergic asthma, respectively.
      We examined whether sequence variants of TBX21 gene are associated with asthma
      and its severity in Indian population. In a hospital-based case-control study,
      240 asthmatic children and 240 healthy controls were investigated for the
      association of TBX21 rs4794067 (C>T) and rs16947078 (G>A) polymorphisms with
      asthma and its severity using PCR-restriction fragment length polymorphism
      method. Heterozygous (CT) (odds ratio (OR)=2.33; P=0.001) and variant (TT)
      (OR=6.25; P=0.001) genotypes of rs4794067 were demonstrated significant risk of
      asthma. However, in asthma severity variant (TT) genotype revealed significant
      increase risk (intermittent: OR=5.9, P=0.001; mild: OR=8.0, P=0.001; moderate:
      OR=3.2, P=0.041; and severe: OR=43.6, P=0.001) in all subgroups. Furthermore,
      haplotypes TG (OR=2.83; P=0.001) and TA (OR=2.54; P=0.001) of TBX21 were
      associated with an increased risk of asthma. Conversely, rs16947078 G>A
      polymorphism was not associated with any asthma/asthma severity risk. These data
      suggest that TBX21 gene variation may modify individual's susceptibility to
      asthma and its severity in Indian population. However, further validation in
      large population-based studies is needed to confirm the finding. 

PMID- 25056816
TI  - Studies on [PtCl2 ]- or [AuCl]-catalyzed cyclization of 1-(Indol-2-yl)-2,3
      allenols: the effects of water/steric hindrance and 1,2-migration selectivity.
AB  - The [PtCl2 ]- or [AuCl]-catalyzed reaction of 1-(indol-2-yl)-2,3-allenols
      occurred smoothly at room temperature to afford a series of poly-substituted
      carbazoles efficiently. Compared with the [PtCl2 ]-catalyzed process, the [AuCl]
      catalyzed reaction represents a significant advance in terms of the scope and the
      selectivity. Selective 1,2-alkyl or aryl migration of the gold carbene
      intermediate was observed: compared with the methyl group, the isopropyl,
      cyclopropyl, cyclobutyl, and cyclohexyl groups migrate exclusively; the
      cyclopropyl group shifts selectively over the ethyl group; the 1,2-migration of a
      non-methyl linear alkyl is faster than methyl group; the phenyl group migrates
      exclusively over methyl or ethyl group. DFT calculations show that water makes
      the elimination of H2 O facile requiring a much lower energy and validates the
      migratory preferences of different alkyl or phenyl groups observed. 

PMID- 25056817
TI  - Fast-growing in-transit melanoma metastasis after intratumoral interleukin-2.

PMID- 25056818
TI  - Limited efficacy of intratumoral IL-2 applied to large melanoma metastases.

PMID- 25056819
TI  - "Immunotherapy of cancer: present status and future promise": Danish Cancer
      Society Symposium, Copenhagen, Denmark, 23rd-25th September 2013.

PMID- 25056820
TI  - Inconsistencies and questionable reliability of the publication "immunotherapy of
      metastatic colorectal cancer with vitamin D-binding protein-derived macrophages
      activating, GcMAF" by Yamamoto et al.

PMID- 25056821
TI  - Measurement of proton resonance frequency shift coefficient during MR-guided
      focused ultrasound on Thiel embalmed tissue.
AB  - PURPOSE: To estimate the value of proton resonance frequency (PRF) shift
      coefficient of explanted Thiel embalmed animal and human tissue used as a
      preclinical model for treatment with MR-guided focused ultrasound (FUS). METHODS:
      Thiel embalmed human liver, ovine liver, and porcine muscle were heated using two
      methods: bulk heating and FUS-induced heating. Phase-referenced PRF thermometry
      was applied during cooling of the tissue to obtain a series of phase difference,
      DeltaPhi, maps. A fiber-optic thermocouple was inserted in the tissue to measure
      the temperature difference, DeltaT. The PRF shift coefficient was calculated from
      the measured DeltaPhi, DeltaT. RESULTS: In the case of bulk heating, the mean
      values (+/-SD) of the PRF coefficient for Thiel embalmed ovine liver, porcine
      muscle, and human liver were: 0.017 (5 * 10-4 ) ppm/ degrees C, 0.015 (6 * 10-4 )
      ppm/ degrees C, and 0.012 (6 * 10-4 ) ppm/ degrees C, respectively. Similar
      values were found in tissues heated with FUS. CONCLUSION: The values of PRF
      coefficient measured for the Thiel embalmed tissue were higher than the values
      for fresh tissue, suggesting that embalming a tissue with Thiel fluid can affect
      PRF thermometry. The chemical composition of the Thiel fluid and the electrical
      conductivity may explain these results. Magn Reson Med 74:260-265, 2015. (c) 2014
      Wiley Periodicals, Inc.

PMID- 25056823
TI  - An examination of the effects of mountaintop removal coal mining on respiratory
      symptoms and COPD using propensity scores.
AB  - Previous research on public health consequences of mountaintop removal (MTR) coal
      mining has been limited by the observational nature of the data. The current
      study used propensity scores, a method designed to overcome this limitation, to
      draw more confident causal inferences about mining effects on respiratory health
      using non-experimental data. These data come from a health survey of 682 adults
      residing in two rural areas of Virginia, USA characterized by the presence or
      absence of MTR mining. Persons with a history of occupational exposure as coal
      miners were excluded. Nine covariates including age, sex, current and former
      smoking, overweight, obesity, high school education, college education, and
      exposure to coal as a home-heating source were selected to estimate propensity
      scores. Propensity scores were tested for balance and then used as weights to
      create quasi-experimental exposed and unexposed groups. Results indicated that
      persons in the mountaintop mining group had significantly (p < 0.0001) elevated
      prevalence of respiratory symptoms and chronic obstructive pulmonary disease. The
      results suggest that impaired respiratory health results from exposure to MTR
      environments and not from other risks.

PMID- 25056822
TI  - Maternal high-protein or high-prebiotic-fiber diets affect maternal milk
      composition and gut microbiota in rat dams and their offspring.
AB  - OBJECTIVE: Maternal gut microbiota and milk composition could modify offspring
      microbiota and therefore disease susceptibility. The effect of maternal high
      protein (HP) or prebiotic diets on maternal milk composition and gut microbiota
      in rat dams and offspring was examined. METHODS: Wistar rat dams were fed a
      control, HP (40% wt/wt), or high-prebiotic-fiber (21.6% wt/wt) (HF) diet
      throughout pregnancy and lactation. Pups were challenged with a high-fat/sucrose
      diet from 14.5 to 22.5 weeks of age. Dam milk was analyzed for fat, protein, and
      oligosaccharides (OS). Fecal microbiota was analyzed in dams at parturition and 2
      weeks post-partum and in offspring at 5 and 22 weeks along with cecal digesta at
      termination. RESULTS: Maternal milk differed only in OS content, each diet group
      being distinguishable. HF1 and HP1 offspring had decreased plasma
      lipopolysaccharide compared with C1. Offspring sex, maternal diet, and time (5
      weeks vs. 22 weeks of age) affected the microbial groups examined. Bifidobacteria
      was higher in HF dams and offspring. CONCLUSIONS: Increasing protein or fiber
      content in maternal diet during pregnancy and lactation modifies milk OS content
      and gut microbiota of dams which may influence establishment of gut microbiota in
      offspring.

PMID- 25056824
TI  - Sonic Hedgehog mutations are not a common cause of congenital hypopituitarism in
      the absence of complex midline cerebral defects.
AB  - CONTEXT AND OBJECTIVE: Sonic Hedgehog (SHH) and GLI2, an obligatory mediator of
      SHH signal transduction, are holoprosencephaly (HPE)-associated genes essential
      in pituitary formation. GLI2 variants have been found in patients with congenital
      hypopituitarism without complex midline cerebral defects (MCD). However, data on
      the occurrence of SHH mutations in these patients are limited. We screened for
      SHH and GLI2 mutations or copy number variations (CNV) in patients with
      congenital hypopituitarism without MCD or with variable degrees of MCD. PATIENTS
      AND METHODS: Detailed data on clinical, laboratory and neuroimaging findings of
      115 patients presenting with congenital hypopituitarism without MCD, septo-optic
      dysplasia or HPE were analysed. The SHH and GLI2 genes were directly sequenced,
      and the presence of gene CNV was analysed by multiplex ligation-dependent probe
      amplification (MLPA). RESULTS: Anterior pituitary deficiency was found in 74% and
      53% of patients with SOD or HPE, respectively. Diabetes insipidus was common in
      patients with HPE (47%) but infrequent in patients with congenital
      hypopituitarism or SOD (7% and 8%, respectively). A single heterozygous nonsense
      SHH mutation (p.Tyr175Ter) was found in a patient presenting with hypopituitarism
      and alobar HPE. No other SHH mutations or CNV were found. Nine GLI2 variations (8
      missense and 1 frameshift) including a homozygous and a compound heterozygous
      variation were found in patients with congenital hypopituitarism or SOD, but not
      in HPE patients. No GLI2 CNV were found. CONCLUSION: SHH mutations or copy number
      variations are not a common cause of congenital hypopituitarism in patients
      without complex midline cerebral defects. GLI2 variants are found in some
      patients with congenital hypopituitarism without complex midline cerebral defects
      or septo-optic dysplasia. However, functional analyses of these variants are
      needed to strengthen genotype-phenotype relationship.

PMID- 25056825
TI  - Combining topological and steric constraints for the preparation of heteroleptic
      copper(I) complexes.
AB  - Heteroleptic copper(I) complexes have been prepared from a macrocyclic ligand
      incorporating a 2,9-diphenyl-1,10-phenanthroline subunit (M30) and two bis
      phosphines, namely bis[(2-diphenylphosphino)phenyl] ether (POP) and 1,3
      bis(diphenylphosphino)propane (dppp). In both cases, the diphenylphosphino
      moieties of the PP ligand are too bulky to pass through the 30-membered ring of
      M30 during the coordination process, hence the formation of C2v-symmetrical
      pseudo-rotaxanes is prevented. When POP is used, X-ray crystal structure analysis
      shows the formation of a highly distorted [Cu(M30)(POP)](+) complex in which the
      POP ligand is only partially threaded through the M30 unit. This compound is
      poorly stable as the Cu(I) cation is not in a favorable coordination environment
      due to steric constraints. By contrast, in the case of dppp, the bis-phosphine
      ligand undergoes both steric and topological constraints and adopts a
      nonchelating coordination mode to generate [Cu2(M30)2(MU-dppp)](BF4)2. This
      compound exhibits metal-to-ligand charge transfer (MLCT) emission characterized
      by a very large Stokes' shift (~200 nm) that is not attributed to a dramatic
      structural distortion between the ground and the emitting states but to very weak
      MLCT absorption transitions at longer wavelengths. Accordingly, [Cu2(M30)2(MU
      dppp)](BF4)2 shows unusually high luminescence quantum yields for Cu(I)
      complexes, both in solution and in the solid state (0.5 and 7 %, respectively).

PMID- 25056826
TI  - Glomerular basement membrane injuries in IgA nephropathy evaluated by double
      immunostaining for alpha5(IV) and alpha2(IV) chains of type IV collagen and low
      vacuum scanning electron microscopy.
AB  - BACKGROUND: The glomerulus contains well-developed capillaries, which are at risk
      of injury due to high hydrostatic pressure, hyperfiltration, hypertension and
      inflammation. However, the pathological alterations of the injured glomerular
      basement membrane (GBM), the main component of the glomerular filtration barrier,
      are still uncertain in cases of glomerulonephritis. METHODS: We examined the
      alterations of the GBM in 50 renal biopsy cases with IgA nephropathy (31.8 +/-
      17.6 years old) using double immunostaining for the alpha2(IV) and alpha5(IV)
      chains of type IV collagen, and examining the ultrastructural alterations by
      transmission electron microscopy (TEM) and low-vacuum scanning electron
      microscopy (LV-SEM). RESULTS: The GBM of IgA nephropathy cases showed various
      morphological and qualitative alterations. In the TEM findings, thinning, gaps,
      rupture, thickening with a lamellar and reticular structure and double contours
      were detected in the GBM. Double immunostaining for alpha5(IV) and alpha2(IV)
      showed thickening of the GBM with reduced alpha5(IV) and increased alpha2(IV), or
      mosaic images of alpha5(IV) and alpha2(IV), and holes, fractures, spiny
      projections and rupture of alpha5(IV) in the GBM. In addition, LV-SEM showed an
      etched image and multiple holes in a widening and wavy GBM. These findings might
      be associated with the development of a brittle GBM in IgA nephropathy.
      CONCLUSION: Glomerular basement membrane alterations were frequently noted in IgA
      nephropathy, and were easily evaluated by double immunostaining for alpha2(IV)
      and alpha5(IV) of type IV collagen and LV-SEM. The application of these analyses
      to human renal biopsy specimens may enhance our understanding of the alterations
      of the GBM that occur in human glomerular diseases.

PMID- 25056827
TI  - Daptomycin susceptibility of 833 strains of Gram-positive cocci from a university
      hospital in Japan (2009-2011).
AB  - The aim of this study was to confirm the daptomycin (DAP) susceptibility of
      bacteria isolated before the launch of DAP in Japan. DAP showed good activity
      against all 833 isolates (MIC90 = 0.25-0.5 mg/L for staphylococci, 0.5-4 mg/L for
      enterococci, and 0.25-0.5 mg/L for streptococci). This is the first report of the
      in vitro activity of DAP against Gram-positive cocci, including methicillin
      resistant Staphylococcus aureus and enterococci, isolated in Japan. 

PMID- 25056829
TI  - Causes, consequences, and kin bias of human group fissions.
AB  - Fissions of human communities are monumental occasions with consequences for
      cultural and genetic variation and divergence through time by means of serial
      founder effects. An ethnographic review shows that most human group fissions are
      fueled primarily by internal political conflict and secondarily by resource
      scarcity. As found for other social animals, human fissions lead to subgroups
      that have higher levels of relatedness as compared with the original community
      because of kin-biased assortment known as the lineal effect. Fission processes
      that increase the average relatedness of subgroups are important because
      relatedness governs how strongly kin/group selection favors social behaviors such
      as warfare, peacekeeping, and other forms of collection action. However, random
      individual assortment is not an appropriate null model for evaluating lineage
      assortment because nuclear families and extended households are expected to
      remain together, which in and of itself forces higher relatedness in smaller
      subgroups. We develop a lineage assortment index where low values represent
      subgroups with coefficients of relatedness near those expected if nuclear and
      extended households had chosen to associate into random groupings. Two fissions
      of Ache villages (Paraguay) are examples of this type of fission with a low
      lineage assortment index not significantly different from zero as evaluated with
      controlled simulations. On the other extreme, a lineage assortment index near
      unity represents a lineal fission that maximizes the relatedness of subgroups
      such as the perfect split of a lineage into sublineages. A fission of Piaroa
      (Venezuela) fits this scenario. While previous discussions of fission have
      emphasized similarities among human studies and even other social mammals, we
      highlight the full range of potential kin bias in the formation of new
      communities. 

PMID- 25056830
TI  - The role of SOX11 immunostaining in confirming the diagnosis of mantle cell
      lymphoma on fine-needle aspiration samples.
AB  - BACKGROUND: Mantle cell lymphoma (MCL) demonstrates cytologic features that
      overlap with those of other types of B-cell non-Hodgkin lymphomas (B-cell NHLs)
      containing small to medium-sized cells. The accurate diagnosis of MCL is
      important because MCL has relatively more aggressive biologic behavior and thus
      requires specific treatment regimens. Fine-needle aspiration (FNA) is used for
      diagnosing or staging lymphoma, often with the help of immunophenotyping by flow
      cytometry. However, the cellularity of an FNA sample may not be high enough for
      flow cytometry, leading to diagnostic difficulty. SOX11 immunostaining is helpful
      in the diagnosis of MCL in histologic sections. However, to the authors'
      knowledge, its diagnostic value for FNA samples has not been studied to date.
      METHODS: Immunostains for SOX11 were performed on 69 FNA cases with final
      diagnoses of MCL (13 cases, including 10 classic type and 3 blastoid variant),
      marginal zone lymphoma (8 cases), follicular lymphoma (10 cases), small
      lymphocytic lymphoma (12 cases), Burkitt lymphoma (9 cases), plasma cell myeloma
      (7 cases), and benign lymph nodes (10 cases). Preparation types included cytospin
      slides (65 cases), direct smears (2 cases), and cell block sections (2 cases).
      The percentage of positive cells (defined as nuclear staining) and staining
      intensity were recorded. RESULTS: All 13 cases of MCL were positive for SOX11
      staining, with 12 cases demonstrating diffuse positivity. All other types of B
      cell NHL cases, plasma cell myelomas, and benign lymph nodes were found to have
      negative results. Weak staining was found in 1 MCL case of blastoid variant.
      CONCLUSIONS: SOX11 immunostaining on FNA samples is highly sensitive and specific
      for MCL and can be used as a reliable adjunct to confirm MCL, especially in a
      recurrent setting.

PMID- 25056828
TI  - Pioneer midbrain longitudinal axons navigate using a balance of Netrin attraction
      and Slit repulsion.
AB  - BACKGROUND: Longitudinal axons grow parallel to the embryonic midline to connect
      distant regions of the central nervous system. Previous studies suggested that
      repulsive midline signals guide pioneer longitudinal axons by blocking their
      entry into the floor plate; however, the role of midline attractants, and whether
      attractant signals may cooperate with repulsive signals, remains unclear. In this
      study we investigated the navigation of a set of pioneer longitudinal axons, the
      medial longitudinal fasciculus, in mouse embryos mutant for the Netrin/Deleted in
      Colorectal Cancer (DCC) attractants, and for Slit repellents, as well as the
      responses of explanted longitudinal axons in vitro. RESULTS: In mutants for
      Netrin1 chemoattractant or DCC receptor signaling, longitudinal axons shifted
      away from the ventral midline, suggesting that Netrin1/DCC signals act
      attractively to pull axons ventrally. Analysis of mutants in the three Slit
      genes, including Slit1/2/3 triple mutants, suggest that concurrent repulsive
      Slit/Robo signals push pioneer axons away from the ventral midline. Combinations
      of mutations between the Netrin and Slit guidance systems provided genetic
      evidence that the attractive and repulsive signals balance against each other.
      This balance is demonstrated in vitro using explant culture, finding that the
      cues can act directly on longitudinal axons. The explants also reveal an
      unexpected synergy of Netrin1 and Slit2 that promotes outgrowth. CONCLUSIONS:
      These results support a mechanism in which longitudinal trajectories are
      positioned by a push-pull balance between opposing Netrin and Slit signals. Our
      evidence suggests that longitudinal axons respond directly and simultaneously to
      both attractants and repellents, and that the combined signals constrain axons to
      grow longitudinally.

PMID- 25056831
TI  - Karyotype structure and chromosome fragility in the grass Phleum echinatum Host.
AB  - Phleum echinatum Host (2n = 2x = 10) is an annual Mediterranean species which
      differs from other representatives of the genus Phleum by reduced chromosome
      number, asymmetric karyotype and unusually high amount of DNA in the genome.
      Chromosomes of this plant were studied using conventional acetic-orcein staining
      and fluorescence in situ hybridization (FISH). FISH showed the major 35S
      ribosomal DNA (rDNA) site at the secondary constriction of satellite chromosome
      (3) and the minor 35S rDNA site near 5S rDNA cluster in the monobrachial
      chromosome 5. Telomeric repeats were detected at all chromosome ends within
      secondary constriction in satellited chromosome 3 and at the centromeric regions
      of chromosomes 1 and 2. Intrachromosomally located telomeric repeats are probably
      traces of chromosomal rearrangements that have shaped P.echinatum genome; they
      were prone to breakage which was manifested in chromosome fragmentation. The most
      distinct telomeric signals, suggesting massive amplification of interstitial
      telomeric sequences (ITRs), were observed at the nucleolar organizer region (NOR)
      of the third chromosome pair. Double FISH confirmed co-localization of telomeric
      and 35S rDNA repeats in this locus characterized by the biggest fragility in the
      karyotype. Fragile sites of P.echinatum, composed of amplified telomeric repeats,
      may bear a resemblance to metazoan rare fragile sites enriched in microsatellite
      repeats. 

PMID- 25056832
TI  - Epidemic Spreading in an Animal Trade Network - Comparison of Distance-Based and
      Network-Based Control Measures.
AB  - This study considered a simple SIR model for the spread of epidemics amongst
      holdings of a producer community in Northern Germany, based on the directed
      network of animal movements. The aim of this study was to evaluate the efficiency
      of different control measures to reduce the epidemic size substantially. The
      currently applied control measures based on the distance to an infected holding
      were compared with the control measures based on the specific network-based
      centrality parameters. We found that network-based measures led to a more
      efficient control of epidemics with a much smaller number of removed holdings. To
      assess the impact of different holding types, the analysed control measures were
      implemented by both including and excluding these holding types. The comparison
      revealed a crucial role of multipliers in the spread of an epidemic. The network
      based control measures depending on the removal by out-degree, outgoing infection
      chain, betweenness centrality and outgoing closeness centrality showed the best
      results: In the three-year network, on average, 2.75, 4.15, 3.73 and 3.43 times
      more holdings had to be removed by the control measures based on the 1, 3, 5 and
      10 km radius to reduce the epidemic to the same size compared with the network
      based control measures. In an area with a higher holding density, the improvement
      of the network-based control measures may become even more obvious. The removal
      of holdings based on the above-mentioned centrality parameters did thus not only
      rapidly decompose the network into fragments, but also reduced the epidemic size
      most efficiently.

PMID- 25056833
TI  - Subchronic administration of atomoxetine causes an enduring reduction in context
      induced relapse to cocaine seeking without affecting impulsive decision making.
AB  - Previous work has established a robust relationship between impulsivity and
      addiction, and revealed that impulsive decision making predisposes the
      vulnerability to cocaine-seeking behavior in rats. An important next step is to
      assess whether elevated relapse vulnerability can be treated via the reduction of
      impulsive decision making. Therefore, this study explored whether subchronic
      atomoxetine treatment can reduce relapse vulnerability by reducing impulsive
      decision making. Rats were trained in the delayed reward task and were subjected
      to 3 weeks of cocaine self-administration. Following drug self-administration,
      animals were divided to different experimental groups and received the
      noradrenaline transporter inhibitor and attention-deficit/hyperactivity disorder
      drug atomoxetine or vehicle subchronically for 20 days. On days 1 and 10 after
      treatment cessation, a context-induced reinstatement test was performed.
      Throughout the entire experiment, changes in impulsive decision making were
      continuously monitored. Subchronic treatment with atomoxetine reduced context
      induced reinstatement both 1 and 10 days after treatment cessation, only in
      animals receiving no extinction training. Interestingly, neither subchronic nor
      acute atomoxetine treatments affected impulsive decision making. Our data
      indicate that the enduring reduction in relapse sensitivity by atomoxetine
      occurred independent of a reduction in impulsive decision making. Nonetheless,
      repeated atomoxetine administration seems a promising pharmacotherapeutical
      strategy to prevent relapse to cocaine seeking in abstinent drug-dependent
      subjects.

PMID- 25056834
TI  - Multiplexed phosphospecific flow cytometry enables large-scale signaling
      profiling and drug screening in blood platelets.
AB  - BACKGROUND: Dissecting the signaling events that contribute to platelet
      activation will increase our understanding of platelet function and aid in the
      development of new antiplatelet agents. However, high-throughput methodology for
      the quantitative analysis of platelet signaling events is still lacking.
      OBJECTIVE: To develop a high-throughput assay for the analysis of platelet
      signaling events in whole blood. METHODS AND RESULTS: We developed a fluorescent
      barcoding protocol to facilitate multiplexing and enable large-scale signaling
      profiling in platelets in whole blood. The methodology allowed simultaneous
      staining and acquisition of 24-96 samples in a single analysis tube with a
      standard flow cytometer. This approach significantly reduced experimental
      numbers, data acquisition time, and antibody consumption, while providing
      automated statistically rich quantitative data on signaling events. Using
      vasodilator-stimulated phosphoprotein (VASP), an established marker of platelet
      inhibition and antiplatelet drug therapy, we demonstrated that the assay could
      detect subtle changes in phosphoVASP-Ser157/239 in response to cAMP-elevating
      agents of varying potency and known modulators of the cAMP signaling cascade. The
      assay could be used with washed platelets or whole blood, analyzed immediately or
      frozen, without any significant change in assay performance. To demonstrate the
      usefulness of the assay as a drug discovery platform, we examined a prostaglandin
      screening library. Our screen of 70 prostaglandin derivatives revealed three
      previously uncharacterized lipids that stimulated phosphorylation of VASP-Ser157.
      Follow-up analyses demonstrated that these agents elevated intraplatelet cAMP and
      inhibited collagen-induced platelet aggregation. CONCLUSIONS: This novel method
      enables rapid, large-scale quantitative signaling profiling and compound
      screening in human platelets present in whole blood.

PMID- 25056835
TI  - Rapid plasma viral suppression in naive HIV-infected patients with high CD4 cells
      and low viraemia initiating a dual nucleoside reverse transcriptase inhibitor
      strategy: a proof-of-concept study.
AB  - OBJECTIVES: To evaluate whether a dual nucleoside reverse transcriptase inhibitor
      (NRTI) strategy can control HIV replication in antiviral therapy (ART)-naive HIV
      infected patients with a high CD4 cell count and a low viral load (VL). METHODS:
      This observational study included all HIV-infected treatment-naive patients with
      a CD4 cell count >300 cells/mm(3), a plasma HIV RNA between 1000 copies/mL and
      30,000 copies/mL and wild-type virus who initiated dual NRTI ART between January
      2008 and December 2012. HIV RNA and CD4 cell count were assessed at Day 0, Week
      (W) 4, W12, W24 and W48. The primary endpoint was the proportion of patients with
      a plasma VL (pVL) <50 copies/mL at W24. RESULTS: Twenty patients were included.
      The median (IQR) baseline characteristics were: time since HIV diagnosis, 25
      months (8-66 months); CD4 cell count, 592 cells/mm(3) (405-798 cells/mm(3)); HIV
      RNA, 10,395 copies/mL (4106-16,566 copies/mL); and HIV DNA, 464 copies/10(6)
      peripheral blood mononuclear cells (195-1168 copies/10(6) PBMC). Nineteen
      patients received tenofovir/emtricitabine and one patient received
      abacavir/lamivudine. At W12, 88% of the patients with available data (n = 16/18,
      95% CI 0.65-0.99) had a pVL <50 copies/mL. Overall, the proportion of patients
      with a pVL <50 copies/mL was 100% (n = 20/20, 95% CI 0.83-1.0) at W24 and 95% (n
      = 18/19, 95% CI 0.74-0.99) at W48 (with one patient lost to follow-up and one
      patient with poor treatment compliance). The median increase in CD4 cells was 83
      cells/mm(3) (40-310 cells/mm(3)). There was no discontinuation of antiretroviral
      therapy for any reason such as lack of efficacy or toxicity. CONCLUSIONS: This
      pilot study suggests that, in patients with a high CD4 cell count and a low VL, a
      dual NRTI strategy may represent a potentially effective treatment strategy to
      control HIV replication. This needs to be confirmed in larger controlled clinical
      studies.

PMID- 25056836
TI  - Serological Survey of Porcine circovirus-2 in Captive Wild Boars (Sus scrofa)
      from Registered Farms of South and South-east Regions of Brazil.
AB  - This study aimed to survey captive wild boars for antibodies against Porcine
      circovirus-2 (PCV-2) in registered farms. Serum samples (n = 1305) were collected
      from 90-day-old wild boars from 118 farms of the Brazilian South-east region,
      including the states of Minas Gerais and Sao Paulo, and South region, including
      the states of Parana, Rio Grande do Sul and Santa Catarina. All herds (100%)
      presented reactive animals, in varying numbers and from low-to-high antibody
      titres, with the occurrence ranging from 82 to 89%. Considering farms, the
      average prevalence was of 84.9% (P < 0.05) and ranged from 54.1 to 94.95%.
      Regarding the geographic regions studied, the prevalence was of 100%, with PCV2
      antibodies detected in wild boars of all regions. This study provides the first
      evidence of PCV2 antibodies in captive wild boars in Brazil. 

PMID- 25056837
TI  - A new manual dispensing system for in meso membrane protein crystallization with
      using a stepping motor-based dispenser.
AB  - A reliable and easy to use manual dispensing system has been developed for the in
      meso membrane protein crystallization method. The system consists of a stepping
      motor-based dispenser with a new microsyringe system for dispensing, which allows
      us to deliver any desired volume of highly viscous lipidic mesophase in the range
      from ~50 to at least ~200 nl. The average, standard deviation, and coefficient of
      variation of 20 repeated deliveries of 50 nl cubic phase were comparable to those
      of a current robotic dispensing. Moreover, the bottom faces of boluses delivered
      to the glass crystallization plate were reproducibly circular in shape, and their
      centers were within about 100 MUm from the center of the crystallization well.
      The system was useful for crystallizing membrane and soluble proteins in meso.

PMID- 25056839
TI  - Polyvinyl alcohol as a biocompatible alternative for the passivation of gold
      nanorods.
AB  - The functionalization of gold nanorods (GNRs) with polymers is essential for both
      their colloidal stability and biocompatibility. However, a bilayer of the toxic
      cationic surfactant cetyl trimethylammonium bromide (CTAB) adsorbed on the
      nanorods complicates this process. Herein, we report on a strategy for the
      biocompatible functionalization of GNRs with a hydrophobic polymeric precursor,
      polyvinyl acetate, which is then transformed into its hydrophilic analogue,
      polyvinyl alcohol. This polymer was chosen due to its well-established
      biocompatibility, tunable "stealth" properties, tunable hydrophobicity, and high
      degree of functionality. The biocompatibility of the functionalized GNRs was
      tested by exposing them to primary human blood monocyte derived macrophages; the
      advantages of tunable hydrophobicity were demonstrated with the long-term stable
      encapsulation of a model hydrophobic drug molecule. 

PMID- 25056838
TI  - The health economics of bladder cancer: an updated review of the published
      literature.
AB  - The purpose of this paper is to provide a current view of the economic burden of
      bladder cancer, with a focus on the cost effectiveness of available
      interventions. This review updates a previous systematic review and includes 72
      new papers published between 2000 and 2013. Bladder cancer continues to be one of
      the most common and expensive malignancies. The annual cost of bladder cancer in
      the USA during 2010 was $US4 billion and is expected to rise to $US5 billion by
      2020. Ten years ago, urinary markers held the potential to lower treatment costs
      of bladder cancer. However, subsequent real-world experiments have demonstrated
      that further work is necessary to identify situations in which these technologies
      can be applied in a cost-effective manner. Adjunct cytology remains a part of
      diagnostic standard of care, but recent research suggests that it is not cost
      effective due to its low diagnostic yield. Analysis of intravesical chemotherapy
      after transurethral resection of bladder tumor (TURBT), neo-adjuvant therapy for
      cystectomy, and robot-assisted laparoscopic cystectomy suggests that these
      technologies are cost effective and should be implemented more widely for
      appropriate patients. The existing literature on the cost effectiveness of
      bladder cancer treatments has improved substantially since 2000. The body of work
      now includes many new models, registry analyses, and real-world studies. However,
      there is still a need for new implementation guidelines, new risk modeling tools,
      and a better understanding of the empirical burden of bladder cancer. 

PMID- 25056840
TI  - Use of a stress-minimisation paradigm in high cell density fed-batch Escherichia
      coli fermentations to optimise recombinant protein production.
AB  - Production of recombinant proteins is an industrially important technique in the
      biopharmaceutical sector. Many recombinant proteins are problematic to generate
      in a soluble form in bacteria as they readily form insoluble inclusion bodies.
      Recombinant protein solubility can be enhanced by minimising stress imposed on
      bacteria through decreasing growth temperature and the rate of recombinant
      protein production. In this study, we determined whether these stress
      minimisation techniques can be successfully applied to industrially relevant high
      cell density Escherichia coli fermentations generating a recombinant protein
      prone to forming inclusion bodies, CheY-GFP. Flow cytometry was used as a routine
      technique to rapidly determine bacterial productivity and physiology at the
      single cell level, enabling determination of culture heterogeneity. We show that
      stress minimisation can be applied to high cell density fermentations (up to a
      dry cell weight of >70 g L(-1)) using semi-defined media and glucose or glycerol
      as carbon sources, and using early or late induction of recombinant protein
      production, to produce high yields (up to 6 g L(-1)) of aggregation-prone
      recombinant protein in a soluble form. These results clearly demonstrate that
      stress minimisation is a viable option for the optimisation of high cell density
      industrial fermentations for the production of high yields of difficult-to
      produce recombinant proteins, and present a workflow for the application of
      stress-minimisation techniques in a variety of fermentation protocols. 

PMID- 25056841
TI  - Decrease in sarcoplasmic reticulum calcium content, not myofilament function,
      contributes to muscle twitch force decline in isolated cardiac trabeculae.
AB  - We set out to determine the factors responsible for twitch force decline in
      isolated intact rat cardiac trabeculae. The contractile force of trabeculae
      declined over extended periods of isometric twitch contractions. The force
      frequency relationship within the frequency range of 4-8 Hz, at 37  degrees C,
      became more positive and the frequency optimum shifted to higher rates with this
      decline in baseline twitch tensions. The post-rest potentiation (37  degrees C),
      a phenomenon highly dependent on calcium handling mechanisms, became more
      pronounced with decrease in twitch tensions. We show that the main abnormality
      during muscle run-down was not due to a deficit in the myofilaments; maximal
      tension achieved using a K(+) contracture protocol was either unaffected or only
      slightly decreased. Conversely, the sarcoplasmic reticulum (SR) calcium content,
      as assessed by rapid cooling contractures (from 27 to 0  degrees C), decreased,
      and had a close association with the declining twitch tensions (R(2) ~ 0.76). SR
      Ca(2+)-ATPase, relative to Na(+)/Ca(2+) exchanger activity, was not altered as
      there was no significant change in paired rapid cooling contracture ratios.
      Furthermore, confocal microscopy detected no abnormalities in the overall
      structure of the cardiomyocytes and t-tubules in the cardiac trabeculae (~23 
      degrees C). Overall, the data indicates that the primary mechanism responsible
      for force run-down in multi-cellular cardiac preparations is a decline in the SR
      calcium content and not the maximal tension generation capability of the
      myofilaments.

PMID- 25056842
TI  - A Comparison of Dynamics in Two Models for the Spread of a Vector-Borne Disease.
AB  - In 2007, bluetongue virus (BTV) was introduced to both Denmark (DK) and the
      United Kingdom (UK). For this reason, simulation models were built to predict
      scenarios for future incursions. The DK and UK models have a common description
      of within-herd dynamics, but differ greatly in their descriptions of between-herd
      spread, one using an explicit representation of vector dispersal, the other a
      transmission kernel. Here, we compare model predictions for the dynamics of
      bluetongue in the UK, based on the 2007 incursion and vaccination rollout in
      2008. We demonstrate how an agent-based model shows greater sensitivity to the
      level of vaccine uptake and has lower variability compared with a kernel-based
      model. However, a model using a transmission kernel requires less detailed data
      and is often faster. 

PMID- 25056843
TI  - Hexacoordinate nickel(II)/(III) complexes that mimic the catalytic cycle of
      nickel superoxide dismutase.
AB  - A functional model complex of nickel superoxide dismutase (NiSOD) with a non
      peptide ligand which mimics the full catalytic cycle of NiSOD is unknown.
      Similarly, it has not been fully elucidated whether NiSOD activity is a result of
      an outer- or inner-sphere electron-transfer mechanism. With this in mind, two
      octahedral nickel(II)/(III) complexes of a bis-tridentate N2 S donor carboxamide
      ligand, N-2-phenylthiophenyl-2'-pyridinecarboxamide (HL(Ph)), have been
      synthesized, structurally characterized, and their SOD activities examined. These
      complexes mimic the full catalytic cycle of NiSOD. Electrochemical experiments
      support an outer-sphere electron-transfer mechanism for their SOD activity.

PMID- 25056844
TI  - Self-reported STIs and sexual health checks in a cross-sectional study of gay and
      bisexual men in New Zealand.
AB  - OBJECTIVES: To determine the incidence of self-reported sexually transmitted
      infections (STIs) and sexual health checks in community and internet samples of
      New Zealand gay, bisexual and other men who have sex with men (MSM) and factors
      associated with these. METHODS: We analysed anonymous self-completed data from
      3138 MSM who participated in the location-based Gay Auckland Periodic Sex Survey
      (GAPSS) and the internet-based Gay Online Sex Survey (GOSS) undertaken in
      February 2011. RESULTS: Overall 8.2% of the participants reported at least one
      STI in the previous 12 months, which did not differ significantly by demographic
      factors or HIV status. While having anal sex and more partners were associated
      with more STI, after adjustment for the number of partners, the type of partner
      (regular or casual) was not. Medium and low condom users reported STIs more than
      high condom users, regardless of partner type. Overall 40% had a sexual health
      check-up without an STI diagnosed in the past year, with similar numbers
      attending general practice and sexual health clinics. Having a check-up was lower
      among Pacific and Asian men, those identifying as bisexual and recruited online.
      While those with more partners, having anal intercourse and diagnosed with HIV
      were more likely to go for a check-up, those using condoms less often were not.
      CONCLUSIONS: STIs are commonly reported in this community sample of MSM but will
      underestimate the true incidence due to asymptomatic infection. Screening for
      STIs outside sexual health clinics should be normalised for MSM and made
      accessible, safe and relevant.

PMID- 25056845
TI  - The impact of an interdisciplinary electroencephalogram educational initiative
      for critical care trainees.
AB  - PURPOSE: The purpose of this study is to evaluate the effectiveness of an
      interdisciplinary electroencephalogram (EEG) educational module for critical care
      training. Electroencephalogram is increasingly used for diagnosis, monitoring,
      and treatment decisions in critically ill patients with neurologic and
      nonneurologic disorders. Continuous EEG monitoring has an expanded role in the
      intensive care unit as an additional evaluation tool for critically ill patients
      with altered mental status. MATERIALS AND METHODS: During a neurosurgical
      intensive care rotation, pulmonary critical care fellows participated in an EEG
      curriculum covering didactics, clinical exposure, and EEG interpretations. Using
      25-question evaluation tools, including EEG interpretations, participants were
      assessed before EEG instruction and after curriculum completion. RESULTS: Nine
      fellows completed the pilot study. Evaluation scores increased from 7.56+/-2.24
      to 16.67+/-2.96 (P<.001). CONCLUSIONS: An interdisciplinary approach was
      effective for increasing EEG knowledge in critical care fellows as measured by
      the assessment tools. As an added potential benefit, the pulmonary fellows also
      learned about sleep disorder-related EEG. This model can be replicated in other
      institutions for trainees of other specialties interested in critical care.

PMID- 25056846
TI  - "As good as dead" and is that good enough? Public attitudes toward brain death.

PMID- 25056847
TI  - Expressional changes of genes and miRNA in common megakaryocyte-erythroid
      progenitors from lower-risk myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is a stem cell tumor characterized by dysplastic
      features and ineffective hematopoiesis in the early phase and leukemic
      progression in the late phase. Speculating that differences in the expression of
      genes and microRNA (miRNA) in control and MDS-derived erythroid progenitors may
      cause ineffective erythropoiesis, we sorted common megakaryocyte-erythroid
      progenitors (MEPs) in bone marrow cells from three lower-risk MDS patients, and
      compared expression levels of genes and miRNA with those from controls. In
      apoptosis-related pathways, the expression of some pro-apoptotic genes, such as
      cell death-inducing DFFA-like effector A, caspase 5, and Fas ligand, was elevated
      in MDS-derived MEPs, while those of anti-apoptotic CD40 and tumor necrosis factor
      were lower. In hematopoiesis-regulating pathways, RUNX1 and ETV6 genes showed
      reduced expression. Expression profiling revealed that three and 35 miRNAs were
      significantly up- and down-regulated in MDS-derived MEPs. MIR9 exhibited robust
      expression in MEPs and CD71+GlyA+ erythroid cells derived from one of the three
      patients. Interestingly, overexpression of MIR9 inhibited the accumulation of
      hemoglobin in UT-7/GM cells. Some of these alterations in gene and miRNA
      expression may contribute to the pathogenesis of ineffective hematopoiesis in
      lower-risk MDS and provide molecular markers for sub-classification and making a
      prognosis. 

PMID- 25056848
TI  - An international collaborative study to establish the World Health Organization
      2nd International Standard for Factor VII Concentrate: communication from the SSC
      of the ISTH.

PMID- 25056849
TI  - Feleucin-BO1: a novel antimicrobial non-apeptide amide from the skin secretion of
      the toad, Bombina orientalis, and design of a potent broad-spectrum synthetic
      analogue, feleucin-K3.
AB  - Feleucins-BV1 and -BV2 are recently described prototypes of a novel antimicrobial
      non-apeptide (AMP) family identified in the skin secretion of the bombinid toad,
      Bombina variegata. They are encoded on different precursors that also encode a
      novel bombinin. Here we describe the identification of feleucin-BO1
      (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named
      feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion
      of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a
      reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 MUm) but was
      inactive (> 250 MUm) against the Gram-negative bacterium, Escherichia coli, and
      the yeast, Candida albicans. This pattern of activity was similar to that of the
      prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3
      (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of
      feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with
      significantly enhanced potency and spectrum of activity. The MICs of F-K3 against
      the reference micro-organisms were 7 MUm (S. aureus), 14 MUm (E. coli) and 7 MUm
      (C. albicans). These data indicate that the skin secretions of amphibians can
      continue to provide novel peptide templates for the rational design of analogues
      with possible therapeutic utility.

PMID- 25056850
TI  - Cytoreductive surgery under aminolevulinic acid-mediated photodynamic diagnosis
      plus hyperthermic intraperitoneal chemotherapy in patients with peritoneal
      carcinomatosis from ovarian cancer and primary peritoneal carcinoma: results of a
      phase I trial.
AB  - BACKGROUND: We conducted a phase I clinical trial to evaluate the sensitivity,
      specificity, and safety of cytoreductive surgery (CRS) under aminolevulinic acid
      mediated photodynamic diagnosis (ALA-PDD) plus hyperthermic intraperitoneal
      chemotherapy (HIPEC) on 20 patients with peritoneal carcinomatosis (PC) from
      ovarian cancer and primary peritoneal carcinoma (PPC). PATIENTS AND METHODS:
      Patients took 5-aminolevulinic acid (5-ALA) at a dose of 20 mg/kg orally with 50
      mL of water 2 h before surgery. During surgery, the abdominal cavity was observed
      under blue light (wavelength of 440 nm) before and after CRS plus HIPEC.
      Specimens were excised and submitted for pathological examination to evaluate the
      specificity of ALA-PDD. Postoperative course was closely monitored and detailed
      information was recorded. RESULTS: CRS under ALA-PDD plus HIPEC was performed 21
      times in 20 patients with PC (16 ovarian cancer, 4 PPC) between June 2011 and
      October 2013. With the exception of 1 (5 %) patient, strong red fluorescence was
      detected in 19 patients with ovarian cancer, with a sensitivity of 95 %. All
      specimens from red fluorescent lesions were invaded by cancer cells, with a
      specificity of 100 %. No severe adverse events occurred during the perioperative
      period, with the exception of some abnormal laboratory results and mild
      complications. All patients were alive until the last follow-up. CONCLUSION: ALA
      PDD provided a high sensitivity and specificity in detecting peritoneal
      metastasis in patients with PC from ovarian serous carcinoma and PPC. CRS under
      ALA-PDD plus HIPEC was a feasible and safe treatment option for patients with PC
      from ovarian cancer and PPC.

PMID- 25056851
TI  - Calcifications on mammogram do not correlate with tumor size after neoadjuvant
      chemotherapy.
AB  - INTRODUCTION: Calcifications can be indicative of malignancy, but calcifications
      also can be a byproduct of necrotic tissue as cancer cells die. Current treatment
      regimens require excision of calcifications. The objective of this study was to
      examine the correlation between the extent of calcification on mammography and
      actual tumor size after neoadjuvant chemotherapy (NAC) as well as magnetic
      resonance imaging (MRI) for comparison. METHODS: We retrospectively reviewed all
      patients at the University of California, San Diego, who underwent NAC for breast
      cancer between 2007 and 2013. Pearson correlation coefficients were computed
      between breast imaging and pathological measurements. RESULTS: There were 136
      patients total. Average age was 51 years. Fifty-three patients had calcifications
      on imaging (calc+); 83 did not (calc-). In the calc- group, extent of disease
      measured by mammogram (MMG) and MRI correlated moderately well with pathological
      tumor size (0.46 and 0.48, p = not significant). In the calc+ group, MRI was more
      likely to correlate with pathology than MMG (0.55 vs. -0.12, p = 0.01). Twenty
      five calc+ patients had increased calcification after NAC; six of these had
      complete pathologic response. MRI correlated better with tumor size on pathology
      in patients with anti-HER2neu-based regimens than in patients with cytotoxic
      chemotherapy-alone regimens (0.88 vs. 0.4, p = 0.0001). MRI also is more accurate
      at predicting pathological tumor size in patients with triple negative disease (p
      = 0.002). CONCLUSIONS: Magnetic resonance imaging correlated well while MMG
      calcification measurements correlated poorly with tumor size on final pathology.
      Extent of calcifications on diagnostic mammography may not be accurate in
      preoperative evaluation of breast cancers after NAC.

PMID- 25056853
TI  - Protecting the green behind the gold: catchment-wide restoration efforts
      necessary to achieve nutrient and sediment load reduction targets in Gold Coast
      City, Australia.
AB  - The Gold Coast City is the tourist center of Australia and has undergone rapid
      and massive urban expansion over the past few decades. The Broadwater estuary, in
      the heart of the City, not only offers an array of ecosystems services for many
      important aquatic wildlife species, but also supports the livelihood and
      lifestyles of residents. Not surprisingly, there have been signs of imbalance
      between these two major services. This study combined a waterway hydraulic and
      pollutant transport model to simulate diffuse nutrient and sediment loads under
      past and future proposed land-use changes. A series of catchment restoration
      initiatives were modeled in an attempt to define optimal catchment scale
      restoration efforts necessary to protect and enhance the City's waterways. The
      modeling revealed that for future proposed development, a business as usual
      approach to catchment management will not reduce nutrient and sediment loading
      sufficiently to protect the community values. Considerable restoration of upper
      catchment tributaries is imperative, combined with treatment of stormwater flow
      from intensively developed sub-catchment areas. Collectively, initiatives
      undertaken by regulatory authorities to date have successfully reduced nutrient
      and sediment loading reaching adjoining waterways, although these programs have
      been ad hoc without strategic systematic planning and vision. Future conservation
      requires integration of multidisciplinary science and proactive management driven
      by the high ecological, economical, and community values placed on the City's
      waterways. Long-term catchment restoration and conservation planning requires an
      extensive budget (including political and societal support) to handle ongoing
      maintenance issues associated with scale of restoration determined here. 

PMID- 25056852
TI  - D-serine plasma concentration is a potential biomarker of (R,S)-ketamine
      antidepressant response in subjects with treatment-resistant depression.
AB  - RATIONALE: (R,S)-ketamine is a rapid and effective antidepressant drug that
      produces a response in two thirds of patients with treatment-resistant depression
      (TRD). The underlying biochemical differences between a (R,S)-ketamine responder
      (KET-R) and non-responder (KET-NR) have not been definitively identified but may
      involve serine metabolism. OBJECTIVES: The aim of the study was to examine the
      relationship between baseline plasma concentrations of D-serine and its precursor
      L-serine and antidepressant response to (R,S)-ketamine in TRD patients. METHODS:
      Plasma samples were obtained from 21 TRD patients at baseline, 60 min before
      initiation of the (R,S)-ketamine infusion. Patients were classified as KET-Rs (n
      = 8) or KET-NRs (n = 13) based upon the difference in Montgomery-Asberg
      Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion,
      with response defined as a >=50 % decrease in MADRS score. The plasma
      concentrations of D-serine and L-serine were determined using liquid
      chromatography-mass spectrometry. RESULTS: Baseline D-serine plasma
      concentrations were significantly lower in KET-Rs (3.02 +/- 0.21 MUM) than in KET
      NRs (4.68 +/- 0.81 MUM), p < 0.001. A significant relationship between baseline D
      serine plasma concentrations and percent change in MADRS at 230 min was
      determined using a Pearson correlation, r = 0.77, p < 0.001, with baseline D
      serine explaining 60 % of the variance in (R,S)-ketamine response. The baseline
      concentrations of L-serine (L-Ser) in KET-Rs were also significantly lower than
      those measured in KET-NRs (66.2 +/- 9.6 MUM vs 242.9 +/- 5.6 MUM, respectively; p
      < 0.0001). CONCLUSIONS: The results demonstrate that the baseline D-serine plasma
      concentrations were significantly lower in KET-Rs than in KET-NRs and suggest
      that this variable can be used to predict an antidepressant response following
      (R,S)-ketamine administration.

PMID- 25056854
TI  - Managing protected areas under climate change--diverse management for
      biodiversity.

PMID- 25056855
TI  - Medical students as EMTs: skill building, confidence and professional formation.
AB  - OBJECTIVE: The first course of the medical curriculum at the Hofstra North Shore
      LIJ School of Medicine, From the Person to the Professional: Challenges,
      Privileges and Responsibilities, provides an innovative early clinical immersion.
      The course content specific to the Emergency Medical Technician (EMT) curriculum
      was developed using the New York State Emergency Medical Technician curriculum.
      Students gain early legitimate clinical experience and practice clinical skills
      as team members in the pre-hospital environment. We hypothesized this novel
      curriculum would increase students' confidence in their ability to perform
      patient care skills and enhance students' comfort with team-building skills early
      in their training. METHODS: Quantitative and qualitative data were collected from
      first-year medical students (n=97) through a survey developed to assess students'
      confidence in patient care and team-building skills. The survey was completed
      prior to medical school, during the final week of the course, and at the end of
      their first year. A paired-samples t-test was conducted to compare self-ratings
      on 12 patient care and 12 team-building skills before and after the course, and a
      theme analysis was conducted to examine open-ended responses. RESULTS: Following
      the course, student confidence in patient care skills showed a significant
      increase from baseline (p<0.05) for all identified skills. Student confidence in
      team-building skills showed a significant increase (p<0.05) in 4 of the 12
      identified skills. By the end of the first year, 84% of the first-year students
      reported the EMT curriculum had 'some impact' to 'great impact' on their patient
      care skills, while 72% reported the EMT curriculum had 'some impact' to 'great
      impact' on their team-building skills. CONCLUSIONS: The incorporation of EMT
      training early in a medical school curriculum provides students with meaningful
      clinical experiences that increase their self-reported level of confidence in the
      performance of patient care skills early in their medical education.

PMID- 25056856
TI  - Renal and bladder ultrasound is important but yields incomplete screening for
      genitourinary abnormalities in young children with urinary tract infection.

PMID- 25056857
TI  - Organocatalytic syntheses of benzoxazoles and benzothiazoles using aryl iodide
      and oxone via C-H functionalization and C-O/S bond formation.
AB  - An organocatalytic protocol for the syntheses of 2-substituted benzoxazoles and
      benzothiazoles is described from alkyl-/arylanilides and alkyl-/arylthioanilides
      using 1-iodo-4-nitrobenzene as catalyst and oxone as an inexpensive and
      environmentally safe terminal oxidant at room temperature in air via oxidative C
      H functionalization and C-O/S bond formation. The procedure is simple and general
      and provides an effective route for the construction of functionalized 2-alkyl
      /arylbenzoxazoles and 2-alkyl-/arylbenzothiazoles with moderate to high yields.
      The synthetic and mechanistic aspects have been described. 

PMID- 25056859
TI  - An improvement index to quantify the evolution of performance in field events.
AB  - The mean of the top 25 performances in 8 men's and 5 women's field events since
      the 1890s showed that performances increased dramatically after the Second World
      War II and subsequently plateaued during the late twentieth century. A
      performance improvement index, developed on the basis of work done, was set to
      100% in 1948. The underlying rise found in all events was modelled using an
      exponential function with a superposition of steps and linear changes to account
      for the introduction of rule changes, drugs testing and the introduction of new
      technologies. The performance improvement index in throwing events increased to
      140.9% compared with 125.8% in jumping events, and women's performance
      improvement always exceeded that of men's. Around half of all events were shown
      to have reached 99.9% of their predicted limit with a majority reaching it within
      the next 25 years. It was concluded that performance will only change in the
      future if an intervention takes place: this could be the emergence of a new
      technology, a rule change or a new athlete population.

PMID- 25056860
TI  - New helical folds in alpha-peptides with alternating chirality.
AB  - In alpha-peptides, the 8/10 helix is theoretically predicted to be energetically
      unstable and has not been experimentally observed so far. Based on our earlier
      studies on 'helical induction' and 'hybrid helices', we have adopted the 'end
      capping' strategy to induce the 8/10 helix in alpha-peptides by using short
      alpha/beta-peptides. Thus, alpha-peptides containing a regular string of alpha
      amino acids with alternating chirality were end capped by alpha/beta-peptides
      with 11/9-helical motifs at the termini. Extensive NMR spectroscopy studies of
      these peptides revealed the presence of a hitherto unknown 8/10-helical pattern;
      the H-bonds in the shorter pseudorings were rather weak. The approach of using
      short helical motifs to induce new mixed helices in alpha-peptides could provide
      avenues for more versatile design strategies. 

PMID- 25056862
TI  - Application of printed circuit board technology to FT-ICR MS analyzer cell
      construction and prototyping.
AB  - Although Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS)
      remains the mass spectrometry platform that provides the highest levels of
      performance for mass accuracy and resolving power, there is room for improvement
      in analyzer cell design as the ideal quadrupolar trapping potential has yet to be
      generated for a broadband MS experiment. To this end, analyzer cell designs have
      improved since the field's inception, yet few research groups participate in this
      area because of the high cost of instrumentation efforts. As a step towards
      reducing this barrier to participation and allowing for more designs to be
      physically tested, we introduce a method of FT-ICR analyzer cell prototyping
      utilizing printed circuit boards at modest vacuum conditions. This method allows
      for inexpensive devices to be readily fabricated and tested over short intervals
      and should open the field to laboratories lacking or unable to access high
      performance machine shop facilities because of the required financial investment.

PMID- 25056861
TI  - Interaction of the Arabidopsis GTPase RabA4c with its effector PMR4 results in
      complete penetration resistance to powdery mildew.
AB  - The (1,3)-beta-glucan callose is a major component of cell wall thickenings in
      response to pathogen attack in plants. GTPases have been suggested to regulate
      pathogen-induced callose biosynthesis. To elucidate the regulation of callose
      biosynthesis in Arabidopsis thaliana, we screened microarray data and identified
      transcriptional upregulation of the GTPase RabA4c after biotic stress. We studied
      the function of RabA4c in its native and dominant negative (dn) isoform in RabA4c
      overexpression lines. RabA4c overexpression caused complete penetration
      resistance to the virulent powdery mildew Golovinomyces cichoracearum due to
      enhanced callose deposition at early time points of infection, which prevented
      fungal ingress into epidermal cells. By contrast, RabA4c(dn) overexpression did
      not increase callose deposition or penetration resistance. A cross of the
      resistant line with the pmr4 disruption mutant lacking the stress-induced callose
      synthase PMR4 revealed that enhanced callose deposition and penetration
      resistance were PMR4-dependent. In live-cell imaging, tagged RabA4c was shown to
      localize at the plasma membrane prior to infection, which was broken in the pmr4
      disruption mutant background, with callose deposits at the site of attempted
      fungal penetration. Together with our interactions studies including yeast two
      hybrid, pull-down, and in planta fluorescence resonance energy transfer assays,
      we concluded that RabA4c directly interacts with PMR4, which can be seen as an
      effector of this GTPase.

PMID- 25056863
TI  - Label scrambling during CID of covalently labeled peptide ions.
AB  - Covalent labeling along with mass spectrometry is finding more use as a means of
      studying the higher order structure of proteins and protein complexes.
      Diethylpyrocarbonate (DEPC) is an increasingly used reagent for these labeling
      experiments because it is capable of modifying multiple residues at the same
      time. Pinpointing DEPC-labeled sites on proteins is typically needed to obtain
      more resolved structural information, and tandem mass spectrometry after protein
      proteolysis is often used for this purpose. In this work, we demonstrate that in
      certain instances, scrambling of the DEPC label from one residue to another can
      occur during collision-induced dissociation (CID) of labeled peptide ions,
      resulting in ambiguity in label site identity. From a preliminary study of over
      30 labeled peptides, we find that scrambling occurs in about 25% of the peptides
      and most commonly occurs when histidine residues are labeled. Moreover, this
      scrambling appears to occur more readily under non-mobile proton conditions,
      meaning that low charge-state peptide ions are more prone to this reaction. For
      all peptides, we find that scrambling does not occur during electron transfer
      dissociation, which suggests that this dissociation technique is a safe
      alternative to CID for correct label site identification. 

PMID- 25056864
TI  - Dual temperature multi-organ recovery from a Maastricht category III donor after
      circulatory death.
AB  - Donation after circulatory death (DCD) makes a significant contribution to the
      transplant activity but is associated with significantly lower organ recovery
      rates and poorer function for the abdominal extra-renal organs compared with
      donation after brain death. Traditionally, DCD organ recovery involves cold
      thoracic and abdominal perfusion with a rapid removal of organs in order to
      minimize the ischemic damage. Novel approaches to organ recovery and preservation
      include the use of normothermic regional perfusion in the donor and ex vivo organ
      preservation. We report a new technique for multi-organ recovery from Maastricht
      category III donors with abdominal normothermic perfusion and concomitant cold
      lung flushing which allows a rapid removal of the lungs with preservation of the
      abdominal normothermic circulation throughout the thoracic procurement. This
      approach could lead to an increased organ recovery and better function for the
      abdominal organs. 

PMID- 25056865
TI  - Sleep therapy is effective in reducing symptoms of depression among adolescents.

PMID- 25056866
TI  - Ticagrelor and the prevention of cardiovascular mortality: more than just
      platelet inhibition?

PMID- 25056867
TI  - The hazard of rounding Cape Horn: is it changing?

PMID- 25056868
TI  - Two decades of experience with the Ross operation in neonates, infants and
      children from the Italian Paediatric Ross Registry.
AB  - OBJECTIVE: Children undergoing Ross operation were expected to have longer
      autograft, but shorter homograft durability compared with adults. In order to
      define the outcome in the second decade after Ross operation in children, a
      nationwide review of 23 years of experience was undertaken. METHODS: 305 children
      underwent Ross operation in 11 paediatric units between 1990 and 2012. Age at
      surgery was 9.4+/-5.7 years, indication aortic stenosis in 103 patients,
      regurgitation in 109 and mixed lesion in 93. 116 (38%) patients had prior
      procedures. Root replacement was performed in 201 patients, inclusion cylinder in
      14, subcoronary grafting in 17 and Ross-Konno in 73. RESULTS: There were 10
      (3.3%) hospital and 12 late deaths (median follow-up 8.7 years). Survival was
      93+/-2% and 89+/-3% and freedom from any reoperation was 76+/-3% and 67+/-6% at
      10 and 15 years. 34 children had autograft 37 reoperations (25 replacement, 12
      repair): three required transplantation after reoperation. Freedom from autograft
      reoperation was 86+/-3% and 75+/-6% at 10 and 15 years. 32 children had right
      heart redo procedures, and only 25 (78%) conduit replacements (15-year freedom
      from replacement, 89+/-4%). Prior operation (p=0.031), subcoronary implant
      (p=0.025) and concomitant surgical procedure (p=0.004) were risk factors for left
      heart reoperation, while infant age (p=0.015) was for right heart. The majority
      (87%) of late survivors were in NYHA class I, 68% free from medication and six
      women had pregnancies. CONCLUSIONS: Despite low hospital risk and satisfactory
      late survival, paediatric Ross operation bears substantial valve-related
      morbidity in the first two decades. Contrary to expectation, autograft
      reoperation is more common than homograft.

PMID- 25056869
TI  - Hydrogen Sulfide Epigenetically Attenuates Homocysteine-Induced Mitochondrial
      Toxicity Mediated Through NMDA Receptor in Mouse Brain Endothelial (bEnd3) Cells.
AB  - Previously we have shown that homocysteine (Hcy) caused oxidative stress and
      altered mitochondrial function. Hydrogen sulfide (H2S) has potent anti
      inflammatory, anti-oxidative, and anti-apoptotic effects. Therefore, in the
      present study we examined whether H2S ameliorates Hcy-induced mitochondrial
      toxicity which led to endothelial dysfunction in part, by epigenetic alterations
      in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to 100 MUM
      Hcy treatment in the presence or absence of 30 MUM NaHS (donor of H2S) for 24 h.
      Hcy-activate NMDA receptor and induced mitochondrial toxicity by increased levels
      of Ca(2+), NADPH-oxidase-4 (NOX-4) expression, mitochondrial dehydrogenase
      activity and decreased the level of nitrate, superoxide dismutase (SOD-2)
      expression, mitochondria membrane potentials, ATP production. To confirm the role
      of epigenetic, 5'-azacitidine (an epigenetic modulator) treatment was given to
      the cells. Pretreatment with NaHS (30 MUM) attenuated the Hcy-induced increased
      expression of DNMT1, DNMT3a, Ca(2+), and decreased expression of DNMT3b in bEND3
      cells. Furthermore, NaHS treatment also mitigated mitochondrial oxidative stress
      (NOX4, ROS, and NO) and restored ATP that indicates its protective effects
      against mitochondrial toxicity. Additional, NaHS significantly alleviated Hcy
      induced LC3-I/II, CSE, Atg3/7, and low p62 expression which confirm its effect on
      mitophagy. Likewise, NaHS also restored level of eNOS, CD31, VE-cadherin and ET-1
      and maintains endothelial function in Hcy treated cells. Molecular inhibition of
      NMDA receptor by using small interfering RNA showed protective effect whereas
      inhibition of H2S production by propargylglycine (PG) (inhibitor of enzyme CSE)
      showed mitotoxic effect. Taken together, results demonstrate that, administration
      of H2S protected the cells from HHcy-induced mitochondrial toxicity and
      endothelial dysfunction.

PMID- 25056870
TI  - Of women seeking assistance for intimate partner violence, those who report
      victimisation during pregnancy are at higher risk of further victimisation.
AB  - Implications for practice and research: The benefits of integrating regular
      intimate partner violence (IPV) screening procedures for pregnant women in
      clinical settings outweigh the cost of minimal time spent conducting assessments.
      Healthcare providers must be trained to conduct IPV assessments and provide
      treatment referrals. Future studies should use larger samples and compare shelter
      populations with general prenatal care.

PMID- 25056871
TI  - Concave impressio ligamenti costoclavicularis ("rhomboid fossa") and its
      prevalence and relevance to clinical practice.
AB  - PURPOSE: The incidence of fossa rhomboidea (RF) and its relevance to clinical
      practice were retrospectively studied in 1,017 cases of patients who endured
      clavicle fractures. The aim of the study was to determine the frequency of
      different types of insertion areas of costoclavicular ligament (LCC) in our
      group, as well as gender distribution. Furthermore, we wanted to investigate
      whether the RF represents a weakened part of clavicle where the fracture
      occurred. Several of our findings in our control group were quite interesting and
      worth mentioning. MATERIALS AND METHODS: 1,017 roentgenograms were analyzed from
      1,027 clavicle fractures of patients from 2 to 90 years of age who were treated
      between 2007 and 2011. RESULTS: Using the Allman classification system, 79% of
      the examined clavicle fractures were identified as type 1, 18.4% as type 2, and
      2.6% as type 3. Statistical analysis did not demonstrate a difference in
      fractures of the clavicle between the right and the left side (47, 53%,
      respectively; p = 0.0570). There was a statistically significant difference in
      the incidence of fractures between the genders (males 71%, females 29 %; p <
      0.0001). The results for the insertion attachment area were as follows for the
      given percent of cases: flat (75.2%); concave (21.1%); convex (3.7%). Those 21.1%
      of concave insertions represent RF. 5.3% of RF cases were between 2 to 10 mm in
      depth. One of the patients with RF had a deepend insertion of the LCC on the
      superior surface of the first rib analogous to RF. The bilateral RF was
      asymmetrical in its appearance. One of the patients suffered from LCC
      enthesopathy. The difference of the distribution of RF throughout the genders was
      10.5% in females and 89.5% in males, marking a difference that is statistically
      significant (p < 0.0001). Only in 0.3%, the fracture line occurred in RF, which
      did not prove the RF to be a weakened point of the fracture (p < 0.0001).
      CONCLUSIONS: RF represents a variety of LCC insertion that is predominantly found
      in male patients, which can be used in the determination of gender in forensic
      analysis. RF is not a weak point for fracture formation. Enthesopathy of the LCC
      together with RF can lead to suspicion concerning the osteolytic process. Biopsy
      of RF should be avoided. Insertion of LCC similar to RF can be exceptionally
      found on the first rib.

PMID- 25056872
TI  - Electrochemical detection of DNA binding by tumor suppressor p53 protein using
      osmium-labeled oligonucleotide probes and catalytic hydrogen evolution at the
      mercury electrode.
AB  - In this paper, we present an electrochemical DNA-protein interaction assay based
      on a combination of protein-specific immunoprecipitation at magnetic beads (MBIP)
      with application of oligonucleotide (ON) probes labeled with an electroactive
      oxoosmium complex (Os,bipy). We show that double-stranded ONs bearing a dT20 tail
      labeled with Os,bipy are specifically recognized by the tumor suppressor p53
      protein according to the presence or absence of a specific binding site (p53CON)
      in the double-stranded segment. We demonstrate the applicability of the Os,bipy
      labeled probes in titration as well as competition MBIP assays to evaluate p53
      relative affinity to various sequence-specific or structurally distinct unlabeled
      DNA substrates upon modulation of the p53-DNA binding by monoclonal antibodies
      used for the immunoprecipitation. To detect the p53-bound osmium-labeled probes,
      we took advantage of a catalytic peak yielded by Os,bipy-modified DNA at the
      mercury-based electrodes, allowing facile determination of subnanogram quantities
      of the labeled oligonucleotides. Versatility of the electrochemical MBIP
      technique and its general applicability in studies of any DNA-binding protein is
      discussed. 

PMID- 25056873
TI  - Preparation and evaluation of monolithic poly(N-vinylcarbazole-co-1,4
      divinylbenzene) capillary columns for the separation of small molecules.
AB  - Short-term polymerization or the so-called low-conversion polymerization was
      applied for the preparation of N-vinylcarbazole (NVC) and 1,4-divinylbenzene
      (DVB) monolithic capillary columns. The synthesis was carried out by thermally
      initiated free radical copolymerization under the influence of inert micro-
      (toluene) and macroporogen (1-decanol) and alpha,alpha'-azoisobutyronitrile
      (AIBN) as radical initiator. The morphological and porous properties were studied
      by scanning electron microscopy (SEM), nitrogen adsorption, and mercury intrusion
      porosimetry (MIP). The copolymerization process was studied by monomer conversion
      measurements. This approach led to increased porosity and specific surface area.
      A specific surface area above 400 m(2)/g of the monolith and a distinct bimodal
      pore size distribution were obtained. The chromatographic performance was
      determined in terms of theoretical plate heights and number of theoretical
      plates. The lowest plate height value was found to be 3.9 MUm (corresponding to
      ~256,000 plates per meter) applying methylparaben utilizing an 80 mm * 0.2 mm
      i.d. monolithic capillary. The developed NVC/DVB monolithic supports showed high
      separation efficiency towards small molecules, which was exemplified applying
      reversed-phase (RP) separation of alkylbenzenes, beta-blockers, flavanoids,
      parabens, and phenones. The loading capacity was analyzed for isocratic
      separation of seven alkylbenzenes and was found to be up to 77 ng total mass of
      alkylbenzenes. Furthermore, a long-term stability test of 1,000 consecutive runs
      was performed and resulted in a maximum variance of 0.97, 0.85, and 0.16 % RSD
      for resolution, peak width at half height, and retention times, respectively. The
      material was proven to have a high permeability of 1.11E-14 m(2), applying water
      as a mobile phase. 

PMID- 25056874
TI  - Molecularly imprinted polymers for cleanup and selective extraction of
      curcuminoids in medicinal herbal extracts.
AB  - This paper describes the synthesis of novel molecularly imprinted polymers
      (MIPs), prepared by a noncovalent imprinting approach, for cleanup and
      preconcentration of curcumin (CUR) and bisdemethoxycurcumin (BDMC) from medicinal
      herbal extracts and further analysis by high-performance liquid chromatography
      with fluorescence detection (HPLC-FLD). Two molecular mimics, a mixture of
      reduced BDMCs and 4-(4-hydroxyphenyl)-2-butanone (HPB), have been synthesized and
      applied as templates for MIP synthesis. The polymers were prepared using N-(2
      aminoethyl) methacrylamide (EAMA) as functional monomer, ethylene glycol
      dimethacrylate (EDMA) as the cross-linker (in a 1:5 molar ratio), and a mixture
      of acetonitrile/dimethylsulfoxide (90%, v/v) as porogen. MIPs prepared using a
      mixture of reduced BDMCs as template showed higher selectivity for CUR and BDMC
      than those obtained with HPB, with imprinting factors of 3.5 and 2.7 for CUR and
      BDMC, respectively, using H2O/acetonitrile (65:35, v/v) as mobile phase. The
      adsorption isotherms for CUR in the MIP and the nonimprinted polymer (NIP) were
      fitted to the Freundlich isotherm model, and the calculated average binding
      affinities for CUR were (17 +/- 2) and (8 +/- 1) mM(-1) for the MIP and the NIP,
      respectively. The polymers were packed into solid-phase extraction (SPE)
      cartridges, and the optimized molecularly imprinted solid-phase extraction (MISPE
      HPLC) with fluorescence detection (FLD) method allowed the extraction of both
      curcuminoids from aqueous samples (50 mM NH4Ac, pH 8.8) followed by a selective
      washing with acetonitrile/NH4Ac, 50 mM at pH 8.8 (30:70%, v/v), and elution with
      3 * 1 mL of MeOH. Good recoveries and precision ranging between 87 and 92%, with
      relative standard deviation (RSD) of <5.3% (n = 3), were obtained after the
      preconcentration of 10-mL solutions containing both CUR and BDMC at
      concentrations in the range of 0-500 MUg L(-1). The optimized method has been
      applied to the analysis of both curcuminoids in medicinal herbal extracts.

PMID- 25056875
TI  - ABC spotlight on carbon nanotubes (CNTs).

PMID- 25056876
TI  - Neuronal STIMulation at rest.
AB  - Almost a decade has passed since first STIM, and later Orai, proteins were
      identified as the molecular constituents of store-operated calcium entry (SOCE).
      Their roles in immune function have been intensely investigated, but the roles of
      STIM and Orai in neuronal cells have been much less clear. Lalonde et al. show
      that when neurons are hyperpolarized or "at rest," constitutive endoplasmic
      reticulum (ER) Ca(2+) release leads to SOCE-mediated activation of neuronal
      transcription factors. Precisely why ER Ca(2+) release is constitutive in neurons
      remains an important question. Irrespective of the answer, this observation
      provides an intriguing new perspective on why a relatively low-abundance, small
      conductance channel such as Orai1 would be important in neurons, which contain a
      relative abundance of voltage-operated Ca(2+) channels. 

PMID- 25056877
TI  - REDD1 enhances protein phosphatase 2A-mediated dephosphorylation of Akt to
      repress mTORC1 signaling.
AB  - The protein kinase mTOR (mechanistic target of rapamycin) in complex 1 (mTORC1)
      promotes cell growth and proliferation in response to anabolic stimuli, including
      growth factors and nutrients. Growth factors activate mTORC1 by stimulating the
      kinase Akt, which phosphorylates and inhibits the tuberous sclerosis complex
      [TSC; which is composed of TSC1, TSC2, and TBC1D7 (Tre2-Bub2-Cdc16 domain family
      member 7)], thereby stimulating the mTORC1 activator Rheb (Ras homolog enriched
      in brain). We identified the mechanism through which REDD1 (regulated in DNA
      damage and development 1) represses the mTORC1 signaling pathway. We found that
      REDD1 promoted the protein phosphatase 2A (PP2A)-dependent dephosphorylation of
      Akt on Thr(308) but not on Ser(473). Consistent with previous studies showing
      that phosphorylation of Akt on Thr(308), but not on Ser(473), is necessary for
      phosphorylation of TSC2, we observed a REDD1-dependent reduction in the
      phosphorylation of TSC2 and subsequently in the activation state of Rheb. REDD1
      and PP2A coimmunoprecipitated with Akt from wild-type but not REDD1 knockout
      mouse embryonic fibroblasts, suggesting that REDD1 may act as a targeting protein
      for the catalytic subunit of PP2A. Furthermore, binding to both Akt and PP2A was
      essential for REDD1 to repress signaling to mTORC1. Overall, the results
      demonstrate that REDD1 acts not only as a repressor of mTORC1 but also as a
      constant modulator of the phosphorylation of Akt in response to growth factors
      and nutrients. 

PMID- 25056878
TI  - The membrane protein Pannexin1 forms two open-channel conformations depending on
      the mode of activation.
AB  - Pannexin1 (Panx1) participates in several signaling events that involve adenosine
      triphosphate (ATP) release, including the innate immune response, ciliary beat in
      airway epithelia, and oxygen supply in the vasculature. The view that Panx1 forms
      a large ATP release channel has been challenged by the association of a low
      conductance, small anion-selective channel with the presence of Panx1. We showed
      that Panx1 membrane channels can function in two distinct modes with different
      conductances and permeabilities when heterologously expressed in Xenopus oocytes.
      When stimulated by potassium ions (K(+)), Panx1 formed a high-conductance channel
      of ~500 pS that was permeable to ATP. Various physiological stimuli can induce
      this ATP-permeable conformation of the channel in several cell types. In
      contrast, the channel had a low conductance (~50 pS) with no detectable ATP
      permeability when activated by voltage in the absence of K(+). The two channel
      states were associated with different reactivities of the terminal cysteine of
      Panx1 to thiol reagents, suggesting different conformations. Single-particle
      electron microscopic analysis revealed that K(+) stimulated the formation of
      channels with a larger pore diameter than those formed in the absence of K(+).
      These data suggest that different stimuli lead to distinct channel structures
      with distinct biophysical properties. 

PMID- 25056879
TI  - Time-resolved dissection of early phosphoproteome and ensuing proteome changes in
      response to TGF-beta.
AB  - Transforming growth factor-beta (TGF-beta) signaling promotes cell motility by
      inducing epithelial-to-mesenchymal transitions (EMTs) in normal physiology and
      development, as well as in pathological conditions, such as cancer. We performed
      a time-resolved analysis of the proteomic and phosphoproteomic changes of
      cultured human keratinocytes undergoing EMT and cell cycle arrest in response to
      stimulation with TGF-beta. We quantified significant changes in 2079 proteins and
      2892 phosphorylation sites regulated by TGF-beta. We identified several proteins
      known to be involved in TGF-beta-induced cellular processes, such as the
      cytostatic response, extracellular matrix remodeling, and epithelial
      dedifferentiation. In addition, we identified proteins involved in other cellular
      functions, such as vesicle trafficking, that were not previously associated with
      TGF-beta signaling. Although many TGF-beta responses are mediated by
      phosphorylation of the transcriptional regulators of the SMAD family by the TGF
      beta receptor complex, we observed rapid kinetics of changes in protein
      phosphorylation, indicating that many responses were mediated through SMAD
      independent TGF-beta signaling. Combined analysis of changes in protein abundance
      and phosphorylation and knowledge of protein interactions and transcriptional
      regulation provided a comprehensive representation of the dynamic signaling
      events underlying TGF-beta-induced changes in cell behavior. Our data suggest
      that in epithelial cells stimulated with TGF-beta, early signaling is a mixture
      of both pro- and antiproliferative signals, whereas later signaling primarily
      inhibits proliferation. 

PMID- 25056880
TI  - Calmodulin-controlled spatial decoding of oscillatory Ca2+ signals by
      calcineurin.
AB  - Calcineurin is responsible for mediating a wide variety of cellular processes in
      response to dynamic calcium (Ca(2+)) signals, yet the precise mechanisms involved
      in the spatiotemporal control of calcineurin signaling are poorly understood.
      Here, we use genetically encoded fluorescent biosensors to directly probe the
      role of cytosolic Ca(2+) oscillations in modulating calcineurin activity dynamics
      in insulin-secreting MIN6 beta-cells. We show that Ca(2+) oscillations induce
      distinct temporal patterns of calcineurin activity in the cytosol and plasma
      membrane vs at the ER and mitochondria in these cells. Furthermore, we found that
      these differential calcineurin activity patterns are determined by variations in
      the subcellular distribution of calmodulin (CaM), indicating that CaM plays an
      active role in shaping both the spatial and temporal aspects of calcineurin
      signaling. Together, our findings provide new insights into the mechanisms by
      which oscillatory signals are decoded to generate specific functional outputs
      within different cellular compartments.

PMID- 25056881
TI  - Immunodominance changes as a function of the infecting dengue virus serotype and
      primary versus secondary infection.
AB  - Dengue virus (DENV) is the causative agent of dengue fever (DF). This disease can
      be caused by any of four DENV serotypes (DENV1 to -4) which share 67 to 75%
      sequence homology with one another. The effect of subsequent infections with
      different serotypes on the T cell repertoire is not fully understood. We utilized
      mice transgenic for human leukocyte antigens (HLA) lacking the alpha/beta
      interferon (IFN-alpha/beta) receptor to study responses to heterologous DENV
      infection. First, we defined the primary T cell response to DENV3 in the context
      of a wide range of HLA molecules. The primary DENV3 immune response recognized
      epitopes derived from all 10 DENV proteins, with a significant fraction of the
      response specific for structural proteins. This is in contrast to primary DENV2
      infection, in which structural proteins are a minor component of the response,
      suggesting differential antigen immunodominance as a function of the infecting
      serotype. We next investigated the effect of secondary heterologous DENV
      infection on the T cell repertoire. In the case of both DENV2/3 and DENV3/2
      heterologous infections, recognition of conserved/cross-reactive epitopes was
      either constant or expanded compared to that in homologous infection.
      Furthermore, in heterologous infection, previous infection with a different
      serotype impaired the development of responses directed to serotype-specific but
      not conserved epitopes. Thus, a detrimental effect of previous heterotypic
      responses might not be due to dysfunctional and weakly cross-reactive epitopes
      dominating the response. Rather, responses to the original serotype might limit
      the magnitude of responses directed against epitopes that are either cross
      reactive to or specific for the most recently infecting serotype. IMPORTANCE:
      DENV transmission occurs in more than 100 countries and is an increasing public
      health problem in tropical and subtropical regions. At present, no effective
      antiviral therapy or licensed vaccine exists, and treatment is largely supportive
      in nature. Disease can be caused by any of the four DENV serotypes (DENV1 to -4),
      which share a high degree of sequence homology with one another. In this study,
      we have addressed the question of how the T cell repertoire changes as a function
      of infections with different serotypes and of subsequent heterologous secondary
      infections. This is of particular interest in the field of dengue viruses, in
      which secondary infections with different DENV serotypes increase the risk of
      severe disease. Our results on the evolution of the immune response after primary
      and secondary infections provide new insights into HLA-restricted T cell
      responses against DENV relevant for the design of a vaccine against DENV.

PMID- 25056884
TI  - Stability determinants of murine cytomegalovirus long noncoding RNA7.2.
AB  - Cytomegalovirus is a ubiquitous herpesvirus that persistently replicates in
      glandular epithelial tissue. Murine cytomegalovirus expresses a 7.2-kb-long
      noncoding RNA (RNA7.2) that is a determinant of viral persistence in the salivary
      gland. RNA7.2 is an extremely long-lived intron, yet the basis of its stability
      is unknown. We present data that localize key sequence determinants of RNA
      stability to the 3' end of RNA7.2 and suggest that stability is a result of
      sustained lariat conformation. 

PMID- 25056882
TI  - Rational design of human metapneumovirus live attenuated vaccine candidates by
      inhibiting viral mRNA cap methyltransferase.
AB  - The paramyxoviruses human respiratory syncytial virus (hRSV), human
      metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are
      responsible for the majority of pediatric respiratory diseases and inflict
      significant economic loss, health care costs, and emotional burdens. Despite
      major efforts, there are no vaccines available for these viruses. The conserved
      region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses
      catalyzes methyltransferase (MTase) activities that typically methylate viral
      mRNAs at positions guanine N-7 (G-N-7) and ribose 2'-O. In this study, we
      generated a panel of recombinant hMPVs carrying mutations in the S
      adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant
      viruses were specifically defective in ribose 2'-O methylation but not G-N-7
      methylation and were genetically stable and highly attenuated in cell culture and
      viral replication in the upper and lower respiratory tracts of cotton rats.
      Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs)
      with defective MTases triggered a high level of neutralizing antibody, and the
      rats were completely protected from challenge with wild-type rhMPV. Collectively,
      our results indicate that (i) amino acid residues in the SAM binding site in the
      hMPV L protein are essential for 2'-O methylation and (ii) inhibition of mRNA cap
      MTase can serve as a novel target to rationally design live attenuated vaccines
      for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. IMPORTANCE:
      Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of
      acute upper and lower respiratory tract infections in humans, particularly in
      infants, children, the elderly, and immunocompromised individuals. Currently,
      there is no licensed vaccine available. A formalin-inactivated vaccine is not
      suitable for these viruses because it causes enhanced lung damage upon
      reinfection with the same virus. A live attenuated vaccine is the most promising
      vaccine strategy for human paramyxoviruses. However, it remains a challenge to
      identify an attenuated virus strain that has an optimal balance between
      attenuation and immunogenicity. Using reverse genetics, we generated a panel of
      recombinant hMPVs that were specifically defective in ribose 2'-O
      methyltransferase (MTase) but not G-N-7 MTase. These MTase-defective hMPVs were
      genetically stable and sufficiently attenuated but retained high immunogenicity.
      This work highlights a critical role of 2'-O MTase in paramyxovirus replication
      and pathogenesis and a new avenue for the development of safe and efficacious
      live attenuated vaccines for hMPV and other human paramyxoviruses.

PMID- 25056883
TI  - Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus
      infection of immortalized keratinocytes.
AB  - The oral cavity is a persistent reservoir for Epstein-Barr virus (EBV) with
      lifelong infection of resident epithelial and B cells. Infection of these cell
      types results in distinct EBV gene expression patterns regulated by epigenetic
      modifications involving DNA methylation and chromatin structure. Regulation of
      EBV gene expression relies on viral manipulation of the host epigenetic machinery
      that may result in long-lasting host epigenetic reprogramming. To identify
      epigenetic events following EBV infection, a transient infection model was
      established to map epigenetic changes in telomerase-immortalized oral
      keratinocytes. EBV-infected oral keratinocytes exhibited a predominantly latent
      viral gene expression program with some lytic or abortive replication. Calcium
      and methylcellulose-induced differentiation was delayed in EBV-positive clones
      and in clones that lost EBV compared to uninfected controls, indicating a
      functional consequence of EBV epigenetic modifications. Analysis of global
      cellular DNA methylation identified over 13,000 differentially methylated CpG
      residues in cells exposed to EBV compared to uninfected controls, with CpG island
      hypermethylation observed at several cellular genes. Although the vast majority
      of the DNA methylation changes were silent, 65 cellular genes that acquired CpG
      methylation showed altered transcript levels. Genes with increased transcript
      levels frequently acquired DNA methylation within the gene body while those with
      decreased transcript levels acquired DNA methylation near the transcription start
      site. Treatment with the DNA methyltransferase inhibitor, decitabine, restored
      expression of some hypermethylated genes in EBV-infected and EBV-negative
      transiently infected clones. Overall, these observations suggested that EBV
      infection of keratinocytes leaves a lasting epigenetic imprint that can enhance
      the tumorigenic phenotype of infected cells. IMPORTANCE: Here, we show that EBV
      infection of oral keratinocytes led to CpG island hypermethylation as an
      epigenetic scar of prior EBV infection that was retained after loss of the virus.
      Such EBV-induced epigenetic modification recapitulated the hypermethylated CpG
      island methylator phenotype (CIMP) observed in EBV-associated carcinomas. These
      epigenetic alterations not only impacted gene expression but also resulted in
      delayed calcium and methylcellulose-induced keratinocyte differentiation.
      Importantly, these epigenetic changes occurred in cells that were not as
      genetically unstable as carcinoma cells, indicating that EBV infection induced an
      epigenetic mutator phenotype. The impact of this work is that we have provided a
      mechanistic framework for how a tumor virus using the epigenetic machinery can
      act in a "hit-and-run" fashion, with retention of epigenetic alterations after
      loss of the virus. Unlike genetic alterations, these virally induced epigenetic
      changes can be reversed pharmacologically, providing therapeutic interventions to
      EBV-associated malignancies.

PMID- 25056885
TI  - Careers in virology: teaching at a primarily undergraduate institution.
AB  - A faculty position at a primarily undergraduate institution requires working with
      undergraduates in both the classroom and the research lab. Graduate students and
      postdoctoral fellows who are interested in such a career should understand that
      faculty at these institutions need to teach broadly and devise research questions
      that can be addressed safely and with limited resources compared to a research I
      university. Aspects of, and ways to prepare for, this career will be reviewed
      herein. 

PMID- 25056886
TI  - Antiviral regulation in porcine monocytic cells at different activation states.
AB  - Monocytic cells, including macrophages and dendritic cells, exist in different
      activation states that are critical to the regulation of antimicrobial immunity.
      Many pandemic viruses are monocytotropic, including porcine reproductive and
      respiratory syndrome virus (PRRSV), which directly infects subsets of monocytic
      cells and interferes with antiviral responses. To study antiviral responses in
      PRRSV-infected monocytic cells, we characterized inflammatory cytokine responses
      and genome-wide profiled signature genes to investigate response pathways in
      uninfected and PRRSV-infected monocytic cells at different activation states. Our
      findings showed suppressed interferon (IFN) production in macrophages in non
      antiviral states and an arrest of lipid metabolic pathways in macrophages at
      antiviral states. Importantly, porcine monocytic cells at different activation
      states were susceptible to PRRSV and responded differently to viral infection.
      Based on Gene Ontology (GO) analysis, two approaches were used to potentiate
      antiviral activity: (i) pharmaceutical modulation of cellular lipid metabolism
      and (ii) in situ PRRSV replication-competent expression of interferon alpha (IFN
      alpha). Both approaches significantly suppressed exogenous viral infection in
      monocytic cells. In particular, the engineered IFN-expressing PRRSV strain
      eliminated exogenous virus infection and sustained cell viability at 4 days
      postinfection in macrophages. These findings suggest an intricate interaction of
      viral infection with the activation status of porcine monocytic cells. An
      understanding and integration of antiviral infection with activation status of
      monocytic cells may provide a means of potentiating antiviral immunity.
      IMPORTANCE: Activation statuses of monocytic cells, including monocytes,
      macrophages (Mphis), and dendritic cells (DCs), are critically important for
      antiviral immunity. Unfortunately, the activation status of porcine monocytic
      cells or how cell activation status functionally interacts with antiviral
      immunity remains largely unknown. This is a significant omission because many
      economically important porcine viruses are monocytotropic, including our focus,
      PRRSV, which alone causes nearly $800 million economic loss annually in the U.S.
      swine industries. PRRSV is ideal for deciphering how monocytic cell activation
      statuses interact with antiviral immunity, because it directly infects subsets of
      monocytic cells and subverts overall immune responses. In this study, we
      systematically investigate the activation status of porcine monocytic cells to
      determine the intricate interaction of viral infection with activation statuses
      and functionally regulate antiviral immunity within the framework of the
      activation paradigm. Our findings may provide a means of potentiating antiviral
      immunity and leading to novel vaccines for PRRS prevention.

PMID- 25056887
TI  - Contribution of silent mutations to thermal adaptation of RNA bacteriophage
      Qbeta.
AB  - Changes in protein function and other biological properties, such as RNA
      structure, are crucial for adaptation of organisms to novel or inhibitory
      environments. To investigate how mutations that do not alter amino acid sequence
      may be positively selected, we performed a thermal adaptation experiment using
      the single-stranded RNA bacteriophage Qbeta in which the culture temperature was
      increased from 37.2 degrees C to 41.2 degrees C and finally to an inhibitory
      temperature of 43.6 degrees C in a stepwise manner in three independent lines.
      Whole-genome analysis revealed 31 mutations, including 14 mutations that did not
      result in amino acid sequence alterations, in this thermal adaptation. Eight of
      the 31 mutations were observed in all three lines. Reconstruction and fitness
      analyses of Qbeta strains containing only mutations observed in all three lines
      indicated that five mutations that did not result in amino acid sequence changes
      but increased the amplification ratio appeared in the course of adaptation to
      growth at 41.2 degrees C. Moreover, these mutations provided a suitable genetic
      background for subsequent mutations, altering the fitness contribution from
      deleterious to beneficial. These results clearly showed that mutations that do
      not alter the amino acid sequence play important roles in adaptation of this
      single-stranded RNA virus to elevated temperature. IMPORTANCE: Recent studies
      using whole-genome analysis technology suggested the importance of mutations that
      do not alter the amino acid sequence for adaptation of organisms to novel
      environmental conditions. It is necessary to investigate how these mutations may
      be positively selected and to determine to what degree such mutations that do not
      alter amino acid sequences contribute to adaptive evolution. Here, we report the
      roles of these silent mutations in thermal adaptation of RNA bacteriophage Qbeta
      based on experimental evolution during which Qbeta showed adaptation to growth at
      an inhibitory temperature. Intriguingly, four synonymous mutations and one
      mutation in the untranslated region that spread widely in the Qbeta population
      during the adaptation process at moderately high temperature provided a suitable
      genetic background to alter the fitness contribution of subsequent mutations from
      deleterious to beneficial at a higher temperature.

PMID- 25056888
TI  - Plasmacytoid dendritic cells mediate synergistic effects of HIV and
      lipopolysaccharide on CD27+ IgD- memory B cell apoptosis.
AB  - The effects of heightened microbial translocation on B cells during HIV infection
      are unknown. We examined the in vitro effects of HIV and lipopolysaccharide (LPS)
      on apoptosis of CD27+ IgD- memory B (mB) cells from healthy controls. In vivo
      analysis was conducted on a cohort of 82 HIV+ donors and 60 healthy controls. In
      vitro exposure of peripheral blood mononuclear cells (PBMCs) to LPS and HIV led
      to mB cell death via the Fas/Fas ligand (FasL) pathway. Plasmacytoid dendritic
      cells (pDCs) produced FasL in response to HIV via binding to CD4 and chemokine
      coreceptors. HIV and LPS increased Fas expression on mB cells in PBMCs, which was
      dependent on the presence of pDCs and monocytes. Furthermore, mB cells purified
      from PBMCs and pretreated with both HIV and LPS were more sensitive to apoptosis
      when cocultured with HIV-treated pDCs. Blocking the interferon receptor (IFNR)
      prevented HIV-stimulated FasL production in pDCs, HIV-plus-LPS-induced Fas
      expression, and apoptosis of mB cells. In vivo or ex vivo, HIV+ donors have
      higher levels of plasma LPS, Fas expression on mB cells, and mB cell apoptosis
      than controls. Correspondingly, in HIV+ donors, but not in controls, a positive
      correlation was found between plasma FasL and HIV RNA levels and between Fas
      expression on mB cells and plasma LPS levels. This work reveals a novel mechanism
      of mB cell apoptosis mediated by LPS and HIV through the Fas/FasL pathway, with
      key involvement of pDCs and type I IFN, suggesting a role for microbial
      translocation in HIV pathogenesis. IMPORTANCE: This study demonstrates that
      lipopolysaccharide (LPS) and type I interferon (IFN) play an important role in
      memory B cell apoptosis in HIV infection. It reveals a previously unrecognized
      role of microbial translocation in HIV pathogenesis.

PMID- 25056889
TI  - New insights into the nonconserved noncoding region of the subtype-determinant
      hemagglutinin and neuraminidase segments of influenza A viruses.
AB  - The noncoding regions (NCRs) of the eight-segmented viral RNAs (vRNAs) of
      influenza A virus consist of the highly conserved promoter region and the
      nonconserved segment-specific NCRs at both the 3' and 5' ends. The roles of the
      segment-specific NCRs of the eight segments have been extensively studied.
      However, the diversities in the same region of the two subtype-determinant
      hemagglutinin (HA) and neuraminidase (NA) segments have received little
      attention. In this study, we bioinformatically analyzed all available NCRs of HA
      and NA vRNAs of influenza A viruses and found that nucleotides in the segment
      specific NCRs of HA and NA vRNAs are subtype specific and vary significantly in
      sequence and length at both the 3' and 5' ends among different subtypes. We then
      systematically studied the biological significance of the HA subtype-specific
      NCRs (HA ssNCRs) of the common HA subtypes (H1 to H7 and H9) in the context of
      the WSN (H1N1) reverse genetics system. We found that the HA ssNCRs play a
      critical role in HA vRNA virion incorporation. Upon HA vRNA incorporation, the 3'
      end HA ssNCR plays a more critical role than the 5'-end HA ssNCR, and no
      stringent compatibility between the two ends is required. Furthermore, our data
      imply that, in addition to a particular nucleotide(s), the length of the HA ssNCR
      is involved in regulating HA vRNA incorporation efficiency. These results provide
      new insights into the HA segment virion incorporation that is critical for the
      emergence of epidemic and pandemic influenza A virus strains. IMPORTANCE: The
      nonconserved noncoding regions (NCRs) of the vRNAs of influenza A virus have been
      extensively studied, whereas the diversities in the nonconserved NCRs of the two
      subtype-determinant segments hemagglutinin (HA) and neuraminidase (NA) have
      received little attention. In this study, we bioinformatically analyzed all
      available NCRs of HA and NA vRNAs and discovered that the HA and NA vRNAs contain
      key subtype signatures in the NCRs. Our functional studies of the HA subtype
      specific NCRs (HA ssNCRs) of the common HA subtypes in the context of WSN virus
      (H1N1) demonstrated that the HA ssNCR modulates virus replication efficiency by
      influencing HA segment virion incorporation. Moreover, we revealed important
      features of the HA ssNCR in determining HA vRNA incorporation efficiency. These
      data not only show new genetic characteristics of influenza A viruses, but also
      provide further evidence for understanding the selective genome packaging of
      influenza virus required for the emergence of epidemic and pandemic influenza
      virus strains.

PMID- 25056890
TI  - Comparison of genotypes I and III in Japanese encephalitis virus reveals distinct
      differences in their genetic and host diversity.
AB  - Japanese encephalitis (JE) is an arthropod-borne disease associated with the
      majority of viral encephalitis cases in the Asia-Pacific region. The causative
      agent, Japanese encephalitis virus (JEV), has been phylogenetically divided into
      five genotypes. Recent surveillance data indicate that genotype I (GI) is
      gradually replacing genotype III (GIII) as the dominant genotype. To investigate
      the mechanism behind the genotype shift and the potential consequences in terms
      of vaccine efficacy, human cases, and virus dissemination, we collected (i) all
      full-length and partial JEV molecular sequences and (ii) associated genotype and
      host information comprising a data set of 873 sequences. We then examined
      differences between the two genotypes at the genetic and epidemiological level by
      investigating amino acid mutations, positive selection, and host range. We found
      that although GI is dominant, it has fewer sites predicted to be under positive
      selection, a narrower host range, and significantly fewer human isolates. For the
      E protein, the sites under positive selection define a haplotype set for each
      genotype that shows striking differences in their composition and diversity, with
      GIII showing significantly more variety than GI. Our results suggest that GI has
      displaced GIII by achieving a replication cycle that is more efficient but is
      also more restricted in its host range. IMPORTANCE: Japanese encephalitis is an
      arthropod-borne disease associated with the majority of viral encephalitis cases
      in the Asia-Pacific region. The causative agent, Japanese encephalitis virus
      (JEV), has been divided into five genotypes based on sequence similarity. Recent
      data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as
      the dominant genotype. Understanding the reasons behind this shift and the
      potential consequences in terms of vaccine efficacy, human cases, and virus
      dissemination is important for controlling the spread of the virus and reducing
      human fatalities. We collected all available full-length and partial JEV
      molecular sequences and associated genotype and host information. We then
      examined differences between the two genotypes at the genetic and epidemiological
      levels by investigating amino acid mutations, positive selection, and host range.
      Our results suggest that GI has displaced GIII by achieving a replication cycle
      that is more efficient but more restricted in host range.

PMID- 25056891
TI  - HIV-1 infection leads to increased transcription of human endogenous retrovirus
      HERV-K (HML-2) proviruses in vivo but not to increased virion production.
AB  - Recent studies suggest that human endogenous retrovirus group K (HERV-K) provirus
      expression plays a role in the pathogenesis of HIV-1 infection. In particular,
      RNA from the HML-2 subgroup of HERV-K proviruses has been reported to be highly
      expressed at the cellular level and detectable in the plasma of HIV-1-infected
      patients, suggestive of virion production and, perhaps, replication. In this
      study, we developed an HML-2-specific quantitative-PCR assay that detects 51 of
      the 89 known HML-2 proviruses in the human genome. Plasma and peripheral blood
      mononuclear cells (PBMCs) from HIV-negative controls and HIV-1-infected patients
      were collected for analysis of HML-2 RNA expression. Contrary to previous
      reports, we did not detect high levels of HML-2 RNA in the plasma of HIV-1
      infected patients, but we did observe a significant increase of HML-2 RNA in
      total PBMCs compared to HIV-negative controls. The level of HML-2 expression in
      PBMCs does not appear to be related to patient use of antiretrovirals or to HIV-1
      plasma RNA, cellular RNA, or cellular DNA levels. To investigate the source of
      HML-2 RNA expression, patient PBMCs were sorted into CD3+ CD4+, CD3+ CD8+, CD3-
      CD14+, and CD3- CD20+ cell subsets and then analyzed for HML-2 RNA levels. No
      single cell subset was enriched for HML-2 RNA expression in HIV-1-infected
      patients, but there appears to be substantial variability in the level of HML-2
      expression depending on the cell type. IMPORTANCE: Here, we report that human
      endogenous retrovirus group K (HERV-K) (HML-2) proviruses are expressed at
      significantly higher levels in peripheral blood mononuclear cells (PBMCs) from
      patients with HIV-1 infection than in those from uninfected individuals. However,
      contrary to previous reports, this expression did not lead to detectable virions
      in the plasma of these patients. In addition, we found that HML-2 proviruses were
      expressed in multiple blood cell types from HIV-1-infected individuals, and the
      magnitude of HML-2 expression was not related to HIV-1 disease markers in this
      patient cohort. These findings may have implications for HML-2-based therapies
      targeting HIV-1 infection.

PMID- 25056892
TI  - Virus-specific memory CD8 T cells provide substantial protection from lethal
      severe acute respiratory syndrome coronavirus infection.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human
      respiratory illness with high morbidity and mortality in 2002-2003. Several
      studies have demonstrated the role of neutralizing antibodies induced by the
      spike (S) glycoprotein in protecting susceptible hosts from lethal infection.
      However, the anti-SARS-CoV antibody response is short-lived in patients who have
      recovered from SARS, making it critical to develop additional vaccine strategies.
      SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV
      infection, a time at which memory B cells and antivirus antibodies were
      undetectable in individuals who had recovered from SARS. In this study, we
      assessed the ability of virus-specific memory CD8 T cells to mediate protection
      against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We
      demonstrate that memory CD8 T cells specific for a single immunodominant epitope
      (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS
      CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs)
      followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding
      S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in
      bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a
      lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced
      multiple effector cytokines (gamma interferon [IFN-gamma], tumor necrosis factor
      alpha [TNF-alpha], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B)
      and reduced lung viral loads. Overall, our results show that SARS-CoV-specific
      memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but
      they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are
      necessary for complete protection. IMPORTANCE: Virus-specific CD8 T cells are
      required for pathogen clearance following primary SARS-CoV infection. However,
      the role of SARS-CoV-specific memory CD8 T cells in mediating protection after
      SARS-CoV challenge has not been previously investigated. In this study, using a
      prime-boost immunization approach, we showed that virus-specific CD8 T cells
      protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus,
      future vaccines against emerging coronaviruses should emphasize the generation of
      a memory CD8 T cell response for optimal protection.

PMID- 25056893
TI  - Virome analysis of Amblyomma americanum, Dermacentor variabilis, and Ixodes
      scapularis ticks reveals novel highly divergent vertebrate and invertebrate
      viruses.
AB  - A wide range of bacterial pathogens have been identified in ticks, yet the
      diversity of viruses in ticks is largely unexplored. In the United States,
      Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis are among the
      principal tick species associated with pathogen transmission. We used high
      throughput sequencing to characterize the viromes of these tick species and
      identified the presence of Powassan virus and eight novel viruses. These included
      the most divergent nairovirus described to date, two new clades of tick-borne
      phleboviruses, a mononegavirus, and viruses with similarity to plant and insect
      viruses. Our analysis revealed that ticks are reservoirs for a wide range of
      viruses and suggests that discovery and characterization of tick-borne viruses
      will have implications for viral taxonomy and may provide insight into tick
      transmitted diseases. IMPORTANCE: Ticks are implicated as vectors of a wide array
      of human and animal pathogens. To better understand the extent of tick-borne
      diseases, it is crucial to uncover the full range of microbial agents associated
      with ticks. Our current knowledge of the diversity of tick-associated viruses is
      limited, in part due to the lack of investigation of tick viromes. In this study,
      we examined the viromes of three tick species from the United States. We found
      that ticks are hosts to highly divergent viruses across several taxa, including
      ones previously associated with human disease. Our data underscore the diversity
      of tick-associated viruses and provide the foundation for further studies into
      viral etiology of tick-borne diseases.

PMID- 25056894
TI  - Deep sequencing of norovirus genomes defines evolutionary patterns in an urban
      tropical setting.
AB  - Norovirus is a highly transmissible infectious agent that causes epidemic
      gastroenteritis in susceptible children and adults. Norovirus infections can be
      severe and can be initiated from an exceptionally small number of viral
      particles. Detailed genome sequence data are useful for tracking norovirus
      transmission and evolution. To address this need, we have developed a whole
      genome deep-sequencing method that generates entire genome sequences from small
      amounts of clinical specimens. This novel approach employs an algorithm for
      reverse transcription and PCR amplification primer design using all of the
      publically available norovirus sequence data. Deep sequencing and de novo
      assembly were used to generate norovirus genomes from a large set of diarrheal
      patients attending three hospitals in Ho Chi Minh City, Vietnam, over a 2.5-year
      period. Positive-selection analysis and direct examination of protein changes in
      the virus over time identified codons in the regions encoding proteins VP1, p48
      (NS1-2), and p22 (NS4) under positive selection and expands the known targets of
      norovirus evolutionary pressure. IMPORTANCE: The high transmissibility and rapid
      evolutionary rate of norovirus, combined with a short-lived host immune
      responses, are thought to be the reasons why the virus causes the majority of
      pediatric viral diarrhea cases. The evolutionary patterns of this RNA virus have
      been described in detail for only a portion of the virus genome and never for a
      virus from a detailed urban tropical setting. We provide a detailed sequence
      description of the noroviruses circulating in three Ho Chi Minh City hospitals
      over a 2.5-year period. This study identified patterns of virus change in known
      sites of host immune response and identified three additional regions of the
      virus genome under selection that were not previously recognized. In addition,
      the method described here provides a robust full-genome sequencing platform for
      community-based virus surveillance.

PMID- 25056895
TI  - Characterization of the mode of action of a potent dengue virus capsid inhibitor.
AB  - Dengue viruses (DV) represent a significant global health burden, with up to 400
      million infections every year and around 500,000 infected individuals developing
      life-threatening disease. In spite of attempts to develop vaccine candidates and
      antiviral drugs, there is a lack of approved therapeutics for the treatment of DV
      infection. We have previously reported the identification of ST-148, a small
      molecule inhibitor exhibiting broad and potent antiviral activity against DV in
      vitro and in vivo (C. M. Byrd et al., Antimicrob. Agents Chemother. 57:15-25,
      2013, doi:10 .1128/AAC.01429-12). In the present study, we investigated the mode
      of action of this promising compound by using a combination of biochemical,
      virological, and imaging-based techniques. We confirmed that ST-148 targets the
      capsid protein and obtained evidence of bimodal antiviral activity affecting both
      assembly/release and entry of infectious DV particles. Importantly, by using a
      robust bioluminescence resonance energy transfer-based assay, we observed an ST
      148-dependent increase of capsid self-interaction. These results were
      corroborated by molecular modeling studies that also revealed a plausible model
      for compound binding to capsid protein and inhibition by a distinct resistance
      mutation. These results suggest that ST-148-enhanced capsid protein self
      interaction perturbs assembly and disassembly of DV nucleocapsids, probably by
      inducing structural rigidity. Thus, as previously reported for other enveloped
      viruses, stabilization of capsid protein structure is an attractive therapeutic
      concept that also is applicable to flaviviruses. IMPORTANCE: Dengue viruses are
      arthropod-borne viruses representing a significant global health burden. They
      infect up to 400 million people and are endemic to subtropical and tropical areas
      of the world. Currently, there are neither vaccines nor approved therapeutics for
      the prophylaxis or treatment of DV infections, respectively. This study reports
      the characterization of the mode of action of ST-148, a small-molecule capsid
      inhibitor with potent antiviral activity against all DV serotypes. Our results
      demonstrate that ST-148 stabilizes capsid protein self-interaction, thereby
      likely perturbing assembly and disassembly of viral nucleocapsids by inducing
      structural rigidity. This, in turn, might interfere with the release of viral RNA
      from incoming nucleocapsids (uncoating) as well as assembly of progeny virus
      particles. As previously reported for other enveloped viruses, we propose the
      capsid as a novel tractable target for flavivirus inhibitors.

PMID- 25056896
TI  - Kaposi's sarcoma-associated herpesvirus ORF18 and ORF30 are essential for late
      gene expression during lytic replication.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several human
      malignances. As saliva is likely the major vehicle for KSHV transmission, we
      studied in vitro KSHV infection of oral epithelial cells. Through infection of
      two types of oral epithelial cells, normal human oral keratinocytes (NHOKs) and
      papilloma-immortalized human oral keratinocyte (HOK16B) cells, we found that KSHV
      can undergo robust lytic replication in oral epithelial cells. By employing de
      novo lytic infection of HOK16B cells, we studied the functions of two previously
      uncharacterized genes, ORF18 and ORF30, during the KSHV lytic cycle. For this
      purpose, an ORF18-deficient virus and an ORF30-deficient virus were generated
      using a mutagenesis strategy based on bacterial artificial chromosome (BAC)
      technology. We found that neither ORF18 nor ORF30 is required for immediately
      early or early gene expression or viral DNA replication, but each is essential
      for late gene expression during both de novo lytic replication and reactivation.
      This critical role of ORF18 and ORF30 in late gene expression was also observed
      during KSHV reactivation. In addition, global analysis of viral transcripts by
      RNA sequencing indicated that ORF18 and ORF30 control the same set of viral
      genes. Therefore, we suggest that these two viral ORFs are involved in the same
      mechanism or pathway that coregulates the viral late genes as a group.
      IMPORTANCE: While KSHV can infect multiple cell types in vitro, only a few can
      support a full lytic replication cycle with progeny virions produced.
      Consequently, KSHV lytic replication is mostly studied through reactivation,
      which requires chemicals to induce the lytic cycle or overexpression of the viral
      transcriptional activator, RTA. In this study, we present a robust de novo lytic
      infection system based on oral epithelial cells. Using this system, we
      demonstrate the role of two viral ORFs, ORF18 and ORF30, in regulating viral gene
      expression during KSHV lytic replication. As the major route of KSHV transmission
      is thought to be via saliva, this new KSHV lytic replication system will have
      important utility in the field.

PMID- 25056897
TI  - Evasion of short interfering RNA-directed antiviral silencing in Musa acuminata
      persistently infected with six distinct banana streak pararetroviruses.
AB  - Vegetatively propagated crop plants often suffer from infections with persistent
      RNA and DNA viruses. Such viruses appear to evade the plant defenses that
      normally restrict viral replication and spread. The major antiviral defense
      mechanism is based on RNA silencing generating viral short interfering RNAs
      (siRNAs) that can potentially repress viral genes posttranscriptionally through
      RNA cleavage and transcriptionally through DNA cytosine methylation. Here we
      examined the RNA silencing machinery of banana plants persistently infected with
      six pararetroviruses after many years of vegetative propagation. Using deep
      sequencing, we reconstructed consensus master genomes of the viruses and
      characterized virus-derived and endogenous small RNAs. Consistent with the
      presence of endogenous siRNAs that can potentially establish and maintain DNA
      methylation, the banana genomic DNA was extensively methylated in both healthy
      and virus-infected plants. A novel class of abundant 20-nucleotide (nt)
      endogenous small RNAs with 5'-terminal guanosine was identified. In all virus
      infected plants, 21- to 24-nt viral siRNAs accumulated at relatively high levels
      (up to 22% of the total small RNA population) and covered the entire circular
      viral DNA genomes in both orientations. The hotspots of 21-nt and 22-nt siRNAs
      occurred within open reading frame (ORF) I and II and the 5' portion of ORF III,
      while 24-nt siRNAs were more evenly distributed along the viral genome. Despite
      the presence of abundant viral siRNAs of different size classes, the viral DNA
      was largely free of cytosine methylation. Thus, the virus is able to evade siRNA
      directed DNA methylation and thereby avoid transcriptional silencing. This
      evasion of silencing likely contributes to the persistence of pararetroviruses in
      banana plants. IMPORTANCE: We report that DNA pararetroviruses in Musa acuminata
      banana plants are able to evade DNA cytosine methylation and transcriptional gene
      silencing, despite being targeted by the host silencing machinery generating
      abundant 21- to 24-nucleotide short interfering RNAs. At the same time, the
      banana genomic DNA is extensively methylated in both healthy and virus-infected
      plants. Our findings shed light on the siRNA-generating gene silencing machinery
      of banana and provide a possible explanation why episomal pararetroviruses can
      persist in plants whereas true retroviruses with an obligatory genome-integration
      step in their replication cycle do not exist in plants.

PMID- 25056898
TI  - Molecular characterization of a lizard adenovirus reveals the first atadenovirus
      with two fiber genes and the first adenovirus with either one short or three long
      fibers per penton.
AB  - Although adenoviruses (AdVs) have been found in a wide variety of reptiles,
      including numerous squamate species, turtles, and crocodiles, the number of
      reptilian adenovirus isolates is still scarce. The only fully sequenced reptilian
      adenovirus, snake adenovirus 1 (SnAdV-1), belongs to the Atadenovirus genus.
      Recently, two new atadenoviruses were isolated from a captive Gila monster
      (Heloderma suspectum) and Mexican beaded lizards (Heloderma horridum). Here we
      report the full genomic and proteomic characterization of the latter, designated
      lizard adenovirus 2 (LAdV-2). The double-stranded DNA (dsDNA) genome of LAdV-2 is
      32,965 bp long, with an average G+C content of 44.16%. The overall arrangement
      and gene content of the LAdV-2 genome were largely concordant with those in other
      atadenoviruses, except for four novel open reading frames (ORFs) at the right end
      of the genome. Phylogeny reconstructions and plesiomorphic traits shared with
      SnAdV-1 further supported the assignment of LAdV-2 to the Atadenovirus genus.
      Surprisingly, two fiber genes were found for the first time in an atadenovirus.
      After optimizing the production of LAdV-2 in cell culture, we determined the
      protein compositions of the virions. The two fiber genes produce two fiber
      proteins of different sizes that are incorporated into the viral particles.
      Interestingly, the two different fiber proteins assemble as either one short or
      three long fiber projections per vertex. Stoichiometry estimations indicate that
      the long fiber triplet is present at only one or two vertices per virion. Neither
      triple fibers nor a mixed number of fibers per vertex had previously been
      reported for adenoviruses or any other virus. IMPORTANCE: Here we show that a
      lizard adenovirus, LAdV-2, has a penton architecture never observed before. LAdV
      2 expresses two fiber proteins-one short and one long. In the virion, most
      vertices have one short fiber, but a few of them have three long fibers attached
      to the same penton base. This observation raises new intriguing questions on
      virus structure. How can the triple fiber attach to a pentameric vertex? What
      determines the number and location of each vertex type in the icosahedral
      particle? Since fibers are responsible for primary attachment to the host, this
      novel architecture also suggests a novel mode of cell entry for LAdV-2.
      Adenoviruses have a recognized potential in nanobiomedicine, but only a few of
      the more than 200 types found so far in nature have been characterized in detail.
      Exploring the taxonomic wealth of adenoviruses should improve our chances to
      successfully use them as therapeutic tools.

PMID- 25056899
TI  - Exosomes from human immunodeficiency virus type 1 (HIV-1)-infected cells license
      quiescent CD4+ T lymphocytes to replicate HIV-1 through a Nef- and ADAM17
      dependent mechanism.
AB  - Resting CD4+ T lymphocytes resist human immunodeficiency virus (HIV) infection.
      Here, we provide evidence that exosomes from HIV-1-infected cells render resting
      human primary CD4+ T lymphocytes permissive to HIV-1 replication. These results
      were obtained with transwell cocultures of HIV-1-infected cells with quiescent
      CD4+ T lymphocytes in the presence of inhibitors of exosome release and were
      confirmed using exosomes purified from supernatants of HIV-1-infected primary
      CD4+ T lymphocytes. We found that the expression of HIV-1 Nef in exosome
      producing cells is both necessary and sufficient for cell activation as well as
      HIV-1 replication in target CD4+ T lymphocytes. We also identified a Nef domain
      important for the effects we observed, i.e., the 62EEEE65 acidic cluster domain.
      In addition, we observed that ADAM17, i.e., a disintegrin and metalloprotease
      converting pro-tumor necrosis factor alpha (TNF-alpha) in its mature form,
      associates with exosomes from HIV-1-infected cells, and plays a key role in the
      HIV-1 replication in quiescent CD4+ T lymphocytes. Treatment with an inhibitor of
      ADAM17 abolished both activation and HIV-1 replication in resting CD4+ T
      lymphocytes. TNF-alpha is the downstream effector of ADAM17 since the treatment
      of resting lymphocytes with anti-TNF-alpha antibodies blocked the HIV-1
      replication. The data presented here are consistent with a model where Nef
      induces intercellular communication through exosomes to activate bystander
      quiescent CD4+ T lymphocytes, thus stimulating viral spread. IMPORTANCE: Overall,
      our findings support the idea that HIV evolved to usurp the exosome-based
      intercellular communication network to favor its spread in infected hosts.

PMID- 25056900
TI  - Inhibition of phosphorylated-STAT1 nuclear translocation and antiviral protein
      expression in human brain vascular adventitial fibroblasts infected with
      varicella-zoster virus.
AB  - In varicella-zoster virus (VZV)-infected primary human brain vascular adventitial
      fibroblasts (BRAFs), levels of beta interferon (IFN-beta,) STAT1, and STAT2
      transcripts as well as STAT1 and STAT2 protein were decreased. IFN-alpha
      transcript levels were increased but not secreted IFN-alpha protein levels.
      Compared to IFN-alpha-treated control results, in VZV-infected BRAFs,
      phosphorylated STAT1 did not translocate to the nucleus, resulting in impaired
      downstream expression of interferon-inducible antiviral Mx1. Overall, VZV
      interference with the type I interferon pathway may promote virus persistence in
      cerebral arteries. 

PMID- 25056901
TI  - Downregulation of microRNA miR-526a by enterovirus inhibits RIG-I-dependent
      innate immune response.
AB  - Retinoic acid-inducible gene I (RIG-I) is an intracellular RNA virus sensor that
      induces type I interferon-mediated host-protective innate immunity against viral
      infection. Although cylindromatosis (CYLD) has been shown to negatively regulate
      innate antiviral response by removing K-63-linked polyubiquitin from RIG-I, the
      regulation of its expression and the underlying regulatory mechanisms are still
      incompletely understood. Here we show that RIG-I activity is regulated by
      inhibition of CYLD expression mediated by the microRNA miR-526a. We found that
      viral infection specifically upregulates miR-526a expression in macrophages via
      interferon regulatory factor (IRF)-dependent mechanisms. In turn, miR-526a
      positively regulates virus-triggered type I interferon (IFN-I) production, thus
      suppressing viral replication, the underlying mechanism of which is the
      enhancement of RIG-I K63-linked ubiquitination by miR-526a via suppression of the
      expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD
      downregulation are blocked by enterovirus 71 (EV71) 3C protein, while ectopic miR
      526a expression inhibits the replication of EV71 virus. The collective results of
      this study suggest a novel mechanism of the regulation of RIG-I activity during
      RNA virus infection by miR-526a and suggest a novel mechanism for the evasion of
      the innate immune response controlled by EV71. IMPORTANCE: RNA virus infection
      upregulates the expression of miR-526a in macrophages through IRF-dependent
      pathways. In turn, miR-526a positively regulates virus-triggered type I IFN
      production and inhibits viral replication, the underlying mechanism of which is
      the enhancement of RIG-I K-63 ubiquitination by miR-526a via suppression of the
      expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD
      downregulation are blocked by enterovirus 71 (EV71) 3C protein; cells with
      overexpressed miR-526a were highly resistant to EV71 infection. The collective
      results of this study suggest a novel mechanism of the regulation of RIG-I
      activity during RNA virus infection by miR-526a and propose a novel mechanism for
      the evasion of the innate immune response controlled by EV71.

PMID- 25056902
TI  - Inducible gene expression in tumors colonized by modified oncolytic vaccinia
      virus strains.
AB  - Exogenous gene induction of therapeutic, diagnostic, and safety mechanisms could
      be a considerable improvement in oncolytic virotherapy. Here, we introduced a
      doxycycline-inducible promoter system (comprised of a tetracycline repressor,
      several promoter constructs, and a tet operator sequence) into oncolytic
      recombinant vaccinia viruses (rVACV), which were further characterized in detail.
      Experiments in cell cultures as well as in tumor-bearing mice were analyzed to
      determine the role of the inducible-system components. To accomplish this, we
      took advantage of the optical reporter construct, which resulted in the
      production of click-beetle luciferase as well as a red fluorescent protein. The
      results indicated that each of the system components could be used to optimize
      the induction rates and had an influence on the background expression levels.
      Depending on the given gene to be induced in rVACV-colonized tumors of patients,
      we discuss the doxycycline-inducible promoter system adjustment and further
      optimization. IMPORTANCE: Oncolytic virotherapy of cancer can greatly benefit
      from the expression of heterologous genes. It is reasonable that some of those
      heterologous gene products could have detrimental effects either on the cancer
      patient or on the oncolytic virus itself if they are expressed at the wrong time
      or if the expression levels are too high. Therefore, exogenous control of gene
      expression levels by administration of a nontoxic inducer will have positive
      effects on the safety as well as the therapeutic outcome of oncolytic
      virotherapy. In addition, it paves the way for the introduction of new
      therapeutic genes into the genome of oncolytic viruses that could not have been
      tested otherwise.

PMID- 25056903
TI  - Short self-interacting N-terminal region of rubella virus capsid protein is
      essential for cooperative actions of capsid and nonstructural p150 proteins.
AB  - Nucleocapsid formation is a primary function of the rubella virus capsid protein,
      which also promotes viral RNA synthesis via an unknown mechanism. The present
      study demonstrates that in infected cells, the capsid protein is associated with
      the nonstructural p150 protein via the short self-interacting N-terminal region
      of the capsid protein. Mutational analyses indicated that hydrophobic amino acids
      in this N-terminal region are essential for its N-terminal self-interaction,
      which is critical for the capsid-p150 association. An analysis based on a
      subgenomic replicon system demonstrated that the self-interacting N-terminal
      region of the capsid protein plays a key role in promoting viral gene expression.
      Analyses using a virus-like particle (VLP) system also showed that the self
      interacting N-terminal region of the capsid protein is not essential for VLP
      production but is critical for VLP infectivity. These results demonstrate that
      the close cooperative actions of the capsid protein and p150 require the short
      self-interacting N-terminal region of the capsid protein during the life cycle of
      the rubella virus. IMPORTANCE: The capsid protein of rubella virus promotes viral
      RNA replication via an unknown mechanism. This protein interacts with the
      nonstructural protein p150, but the importance of this interaction is unclear. In
      this study, we demonstrate that the short N-terminal region of the capsid protein
      forms a homo-oligomer that is critical for the capsid-p150 interaction. These
      interactions are required for the viral-gene-expression-promoting activity of the
      capsid protein, allowing efficient viral growth. These findings provide
      information about the mechanisms underlying the regulation of rubella virus RNA
      replication via the cooperative actions of the capsid protein and p150.

PMID- 25056904
TI  - Making the most of clinical data: reviewing the role of pharmacokinetic
      pharmacodynamic models of anti-malarial drugs.
AB  - Mechanistic within-host models integrating blood anti-malarial drug
      concentrations with the parasite-time profile provide a valuable decision tool
      for determining dosing regimens for anti-malarial treatments, as well as a
      formative component of population-level drug resistance models. We reviewed
      published anti-malarial pharmacokinetic-pharmacodynamic models to identify the
      challenges for these complex models where parameter estimation from clinical
      field data is limited. The inclusion of key pharmacodynamic processes in the
      mechanistic structure adopted varies considerably. These include the life cycle
      of the parasite within the red blood cell, the action of the anti-malarial on a
      specific stage of the life cycle, and the reduction in parasite growth associated
      with immunity. With regard to estimation of the pharmacodynamic parameters, the
      majority of studies simply compared descriptive summaries of the simulated
      outputs to published observations of host and parasite responses from clinical
      studies. Few studies formally estimated the pharmacodynamic parameters within a
      rigorous statistical framework using observed individual patient data. We
      recommend three steps in the development and evaluation of these models. Firstly,
      exploration through simulation to assess how the different parameters influence
      the parasite dynamics. Secondly, application of a simulation-estimation approach
      to determine whether the model parameters can be estimated with reasonable
      precision based on sampling designs that mimic clinical efficacy studies.
      Thirdly, fitting the mechanistic model to the clinical data within a Bayesian
      framework. We propose that authors present the model both schematically and in
      equation form and give a detailed description of each parameter, including a
      biological interpretation of the parameter estimates.

PMID- 25056905
TI  - Distribution of scytonemin in endolithic microbial communities from halite crusts
      in the hyperarid zone of the Atacama Desert, Chile.
AB  - Scytonemin, a UV-screening molecule produced by certain Cyanobacteria to protect
      against harmful UV radiation, was studied in endolithic cyanobacterial colonies
      in the halite crust from one of the driest places on Earth - the hyperarid zone
      of the Atacama Desert. The distribution of the pigment within the evaporitic
      crust was studied in detail by various independent analytical methods: Raman
      spectroscopy (including Raman imaging); advanced microscopic observations
      (fluorescence microscopy, confocal laser scanning microscopy, low-temperature
      scanning electron microscopy); and spectrophotometric analyses. The differences
      in scytonemin biosynthesis were mapped within the colonized interior layers,
      which can be divided into scytonemin-rich and scytonemin-poor zones. A 532 nm
      laser for excitation proved to be an ideal excitation source with which to
      observe the relative content of scytonemin within a particular cell aggregate, as
      well as between different cell aggregates; based on the scytonemin/carotenoid
      Raman signal intensity ratio of selected corroborative bands for these two
      compounds. Significantly, scytonemin was found to accumulate within a decayed
      biomass in the surface portions of the halite crust. These were found to be
      highly enriched in both the absolute scytonemin content (as documented by UV/VIS
      spectrophotometry) and its content relative to other pigments associated with the
      cyanobacterial cells (e.g. carotenoids and chlorophyll). 

PMID- 25056906
TI  - BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity
      against Shigella.
AB  - The X-linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor,
      best known for its anti-apoptotic function in cancer. During apoptosis, XIAP is
      antagonized by SMAC, which is released from the mitochondria upon caspase
      mediated activation of BID. Recent studies suggest that XIAP is involved in
      immune signaling. Here, we explore XIAP as an important mediator of an immune
      response against the enteroinvasive bacterium Shigella flexneri, both in vitro
      and in vivo. Our data demonstrate for the first time that Shigella evades the
      XIAP-mediated immune response by inducing the BID-dependent release of SMAC from
      the mitochondria. Unlike apoptotic stimuli, Shigella activates the calpain
      dependent cleavage of BID to trigger the release of SMAC, which antagonizes the
      inflammatory action of XIAP without inducing apoptosis. Our results demonstrate
      how the cellular death machinery can be subverted by an invasive pathogen to
      ensure bacterial colonization. 

PMID- 25056907
TI  - Identification of putative biomarkers for HIV-associated neurocognitive
      impairment in the CSF of HIV-infected patients under cART therapy determined by
      mass spectrometry.
AB  - We identified and measured proteins in the cerebral spinal fluid (CSF) involved
      in HIV-associated neurological disorders. Protein levels were determined by mass
      spectrometry (MS) in pooled CSF taken from three patient groups (human
      immunodeficiency virus (HIV)-1-infected patients that developed HIV-associated
      neurocognitive disorders (HANDs), HIV-1-infected patients without HAND, and
      healthy controls). Pools were generated from 10 patients each per group. CSF from
      individual patient groups were digested with trypsin and separately labeled using
      with isobaric tags for relative and absolute quantitation (iTRAQ). After
      combining all samples in one, peptides were extensively fractionated by offline
      two-dimensional separation and identified by tandem MS. One hundred and ninety
      three proteins were deemed to be interpretable for quantitation based on
      permutation tests with a 95 % confidence interval with a p value <= 0.05. Using a
      cutoff of 1.5-fold for upregulation and 0.6 for downregulation, 16 proteins were
      differentially expressed in HIV + HAND (reporter p value <=0.05) with seven of
      them previously described as HIV-interacting proteins: endoplasmin, mitochondrial
      damage mediator-BH3-interacting domanin death agonist, orosomucoid,
      apolipoprotein E, metalloproteinase inhibitor 2, peroxiredoxin-2, and the nuclear
      protein, ruvB-like 2. Several previously unidentified proteins with possible
      neurological implication in HIV patients include forming-binding protein 1, C
      reactive protein, leukocyte-associated immunoglobulin receptor 1, renin receptor,
      mediator of RNA polymerase II transcription subunit 14, multimerin-2, alpha-N
      acetylglucosaminidase, caldesmon, and cadherin EGF LAG G-type receptor. Our
      results suggest that not only a few but possibly a combination of biomarkers that
      are highly correlated can predict neurocognitive status in HIV-infected patients
      and might be involved in monocyte or macrophage activation.

PMID- 25056908
TI  - Decipher the dynamic coordination between enzymatic activity and structural
      modulation at focal adhesions in living cells.
AB  - Focal adhesions (FAs) are dynamic subcellular structures crucial for cell
      adhesion, migration and differentiation. It remains an enigma how enzymatic
      activities in these local complexes regulate their structural remodeling in live
      cells. Utilizing biosensors based on fluorescence resonance energy transfer
      (FRET), we developed a correlative FRET imaging microscopy (CFIM) approach to
      quantitatively analyze the subcellular coordination between the enzymatic Src
      activation and the structural FA disassembly. CFIM reveals that the Src kinase
      activity only within the microdomain of lipid rafts at the plasma membrane is
      coupled with FA dynamics. FA disassembly at cell periphery was linearly dependent
      on this raft-localized Src activity, although cells displayed heterogeneous
      levels of response to stimulation. Within lipid rafts, the time delay between Src
      activation and FA disassembly was 1.2 min in cells seeded on low fibronectin
      concentration ([FN]) and 4.3 min in cells on high [FN]. CFIM further showed that
      the level of Src-FA coupling, as well as the time delay, was regulated by cell
      matrix interactions, as a tight enzyme-structure coupling occurred in FA
      populations mediated by integrin alphavbeta3, but not in those by integrin
      alpha5beta1. Therefore, different FA subpopulations have distinctive regulation
      mechanisms between their local kinase activity and structural FA dynamics.

PMID- 25056909
TI  - Autologous fat grafting for breast augmentation in underweight women.
AB  - BACKGROUND: In recent years, there have been reports of success with autologous
      fat grafting to the breast for cosmetic breast enhancement. However, the
      procedure is generally contraindicated in women who are underweight (body mass
      index [BMI]<18.5). OBJECTIVES: The author sought to determine the safety and
      success rate of autologous fat grafting for breast augmentation in underweight
      women. METHODS: Patients who underwent breast augmentation with autologous fat
      grafting and had adequate follow-up time (>=12 months) were assigned to group A
      (BMI>18.5) or group B (BMI<=18.5; underweight). A retrospective analysis was
      performed to compare the safety and effectiveness of fat grafting between the
      study groups. RESULTS: Relative to group A, patients in group B were younger and
      had smaller differences in breast circumference (BCD) both pretreatment and
      posttreatment. The volume of injected fat was significantly smaller in group B.
      The differences in posttreatment complication rates and changes in BCD were not
      statistically significant between the study groups. CONCLUSIONS: The same degree
      of breast enlargement was achieved in both study groups after autologous fat
      grafting for breast augmentation. The rate of posttreatment complications was not
      higher for underweight women. Therefore, it appears that BMI<=18.5 is not a
      contraindication for this procedure. LEVEL OF EVIDENCE: 4.

PMID- 25056910
TI  - Breast striae after cosmetic augmentation.
AB  - BACKGROUND: Breast augmentation is the most popular cosmetic surgery procedure in
      the United States. Postoperative striae is a known but incompletely understood
      complication of breast augmentation. OBJECTIVES: The authors investigated their
      own patient population to discern risk factors for new-onset striae after
      cosmetic breast augmentation. METHODS: A retrospective chart review was performed
      for patients who underwent primary breast augmentation from 2005 to 2012 in a
      single-surgeon practice. Initial chart review revealed that only patients aged
      <=25 years exhibited new striae; therefore, only patients from this age group
      were included. Potential risk factors examined included age, body mass index
      (BMI), oral contraceptive use, time of last menstrual period (LMP), parity,
      smoking and alcohol status, diabetes mellitus, and personal history of striae.
      Implant and surgical factors examined included implant material (silicone vs
      saline), volume, and location (submuscular vs subglandular placement) and the
      site of incision. RESULTS: Of the 549 patients included in the study, 17 (3.10%)
      had new-onset striae, observed at a mean of 58 days postoperatively. The risk of
      striae was statistically significantly higher (P<.05) among patients who were
      younger (3.3 times), were nulliparous (14.38 times), began their LMP>14 days
      before surgery (9.24 times), and had a history of striae (6.11 times). There was
      a strong correlation between new-onset breast striae and implant size, as well as
      BMI (P=.07). CONCLUSIONS: There is a strong correlation between new-onset striae
      and hormone levels, genetic factors, and tissue stretch components in patients
      who undergo cosmetic breast augmentation. This information can be utilized to
      better educate patients about this potential complication. LEVEL OF EVIDENCE: 4.

PMID- 25056911
TI  - An easy way to prepare monolithic inorganic oxide aerogels.
AB  - Inorganic oxide aerogels have unique thermal, optical, electrical, magnetic, and
      chemical properties, which result in them potentially having a broad range of
      applications. However, their preparation is commonly based on a supercritical
      drying method, which greatly limits real applications of aerogels and their
      commercialization. Here we demonstrate a general method for drying wet gels to
      form aerogels that is based on the sublimation of organic solvent. The organic
      solvent must have a low surface tension, undergo sublimation easily, and have a
      high freezing point to allow the rapid synthesis of monolithic inorganic oxide
      aerogels under vacuum conditions. This cost-effective process will facilitate
      application of aerogel materials. This approach may also be used for the
      preparation of other porous materials, whose theoretical and practical
      applications should be investigated. 

PMID- 25056912
TI  - Regulation of Osteoclast Multinucleation by the Actin Cytoskeleton Signaling
      Network.
AB  - Although it is known that osteoclasts are multinucleated cells that are
      responsible for bone resorption, the mechanism by which their size is regulated
      is unclear. We previously reported that an actin-rich superstructure, termed the
      zipper-like structure, specifically appears during the fusion of large osteoclast
      like cells (OCLs). Actin cytoskeleton reorganization in osteoclasts is regulated
      by a signaling network that includes the macrophage colony-stimulating factor (M
      CSF) receptor, a proto-oncogene, Src, and small GTPases. Here, we examined the
      role of actin reorganization in the multinucleation of OCLs differentiated from
      RAW 264.7 cells using various pharmacological agents. Jasplakinolide, which
      stabilizes actin stress fibers, induced the development of small OCLs, and the
      Src inhibitor SU6656 and the dynamin inhibitor dynasore impaired the maintenance
      of the podosome belt and the zipper-like structure. These inhibitors decreased
      the formation of large OCLs but increased the number of small OCLs. M-CSF is
      known to stimulate osteoclast fusion. M-CSF signaling via Src up-regulated Rac1
      activity but down-regulated Rho activity. Rac1 and Rho localized to the center of
      the zipper-like structure. Rho activator II promoted the formation of small OCLs,
      whereas the Rho inhibitor Y27632 promoted the generation of large OCLs. These
      results suggest that the status of the actin cytoskeleton signaling network
      determines the size of OCLs during cell fusion.

PMID- 25056914
TI  - Active causation and the origin of meaning.
AB  - Purpose and meaning are necessary concepts for understanding mind and culture,
      but appear to be absent from the physical world and are not part of the
      explanatory framework of the natural sciences. Understanding how meaning (in the
      broad sense of the term) could arise from a physical world has proven to be a
      tough problem. The basic scheme of Darwinian evolution produces adaptations that
      only represent apparent ("as if") goals and meaning. Here I use evolutionary
      models to show that a slight, evolvable extension of the basic scheme is
      sufficient to produce genuine goals. The extension, targeted modulation of
      mutation rate, is known to be generally present in biological cells and gives
      rise to two phenomena that are absent from the non-living world: intrinsic
      meaning and the ability to initiate goal-directed chains of causation (active
      causation). The extended scheme accomplishes this by utilizing randomness
      modulated by a feedback loop that is itself regulated by evolutionary pressure.
      The mechanism can be extended to behavioural variability as well and thus shows
      how freedom of behaviour is possible. A further extension to communication
      suggests that the active exchange of intrinsic meaning between organisms may be
      the origin of consciousness, which in combination with active causation can
      provide a physical basis for the phenomenon of free will. 

PMID- 25056915
TI  - Amino-functionalized pillar[5]arene.
AB  - The recently introduced pillar[n]arenes have provided chemists with receptors
      that, when incorporated into materials, confer unique properties upon them. The
      symmetrical rims and cylindrical shape of pillar[5]arene begs the question--can
      these pillar-like receptors be linked covalently end-to-end in order to create
      tubular structures by a growth-from-template approach? In our efforts to produce
      these one-dimensional extended structures, we have developed a new method of
      functionalizing pillar[5]arene in which one of the five hydroquinone units is
      converted into a diaminobenzoquinone analogue. The resulting
      diaminopillar[5]arene derivative, which undergoes a stereochemical inversion
      process that is slow on the (1)H NMR timescale, can be chemically modified yet
      further in a direction that is orthogonal to the plane of its methylene bridging
      carbons through the formation of oxazole heterocycles. This strategy has been
      employed to create rigid oligomers that resemble one-dimensional tubular arrays.
      As a proof-of-principle, a rigid pillar[5]arene dimer has been isolated and
      characterized in the solution state as a 1:1 complex with an extended viologen
      for which it acts as a receptor.

PMID- 25056916
TI  - Tetracycline modifies competitive interactions in experimental microcosms
      containing bacteria isolated from freshwater.
AB  - Interspecific microbial interactions are important for community structure,
      function and evolution, but it is not fully understood how interactions among
      bacterial species are influenced by some types of abiotic environmental
      variation, such as exposure to antibiotics. We tested for the effect of an
      antibiotic, tetracycline, on interspecific interactions in vitro among four
      species of aquatic bacteria isolated from European water bodies. Interactions
      among species in experimental microcosms containing artificial lake water (ALW)
      supplemented with glucose were largely competitive, as detected by comparing
      mixed cultures to pure cultures of their constituent species. Sublethal
      concentrations of tetracycline changed the relative competitive abilities of
      different species and revealed considerable variation in antibiotic sensitivity,
      but did not reduce the average strength of competition. Interspecific
      interactions at a given concentration were largely predictable from growth in
      pure cultures and indirect interactions with other species. These results suggest
      that antibiotics such as tetracycline may have important consequences for
      interactions among bacterial species, but in our experiments this was because
      species varied in their capacities for growth in the presence of tetracycline,
      rather than reduced competition at increasing tetracycline concentrations. 

PMID- 25056913
TI  - The inwardly rectifying K+ channel KIR7.1 controls uterine excitability
      throughout pregnancy.
AB  - Abnormal uterine activity in pregnancy causes a range of important clinical
      disorders, including preterm birth, dysfunctional labour and post-partum
      haemorrhage. Uterine contractile patterns are controlled by the generation of
      complex electrical signals at the myometrial smooth muscle plasma membrane. To
      identify novel targets to treat conditions associated with uterine dysfunction,
      we undertook a genome-wide screen of potassium channels that are enriched in
      myometrial smooth muscle. Computational modelling identified Kir7.1 as
      potentially important in regulating uterine excitability during pregnancy. We
      demonstrate Kir7.1 current hyper-polarizes uterine myocytes and promotes
      quiescence during gestation. Labour is associated with a decline, but not loss,
      of Kir7.1 expression. Knockdown of Kir7.1 by lentiviral expression of miRNA was
      sufficient to increase uterine contractile force and duration significantly.
      Conversely, overexpression of Kir7.1 inhibited uterine contractility. Finally, we
      demonstrate that the Kir7.1 inhibitor VU590 as well as novel derivative compounds
      induces profound, long-lasting contractions in mouse and human myometrium; the
      activity of these inhibitors exceeds that of other uterotonic drugs. We conclude
      Kir7.1 regulates the transition from quiescence to contractions in the pregnant
      uterus and may be a target for therapies to control uterine contractility. 

PMID- 25056917
TI  - Molecular basis of crosstalk between oncogenic Ras and the master regulator of
      hematopoiesis GATA-2.
AB  - Disease mutations provide unique opportunities to decipher protein and cell
      function. Mutations in the master regulator of hematopoiesis GATA-2 underlie an
      immunodeficiency associated with myelodysplastic syndrome and leukemia. We
      discovered that a GATA-2 disease mutant (T354M) defective in chromatin binding
      was hyperphosphorylated by p38 mitogen-activated protein kinase. p38 also induced
      multisite phosphorylation of wild-type GATA-2, which required a single
      phosphorylated residue (S192). Phosphorylation of GATA-2, but not T354M,
      stimulated target gene expression. While crosstalk between oncogenic Ras and GATA
      2 has been implicated as an important axis in cancer biology, its mechanistic
      underpinnings are unclear. Oncogenic Ras enhanced S192-dependent GATA-2
      phosphorylation, nuclear foci localization, and transcriptional activation. These
      studies define a mechanism that controls a key regulator of hematopoiesis and a
      dual mode of impairing GATA-2-dependent genetic networks: mutational disruption
      of chromatin occupancy yielding insufficient GATA-2, and oncogenic Ras-mediated
      amplification of GATA-2 activity. 

PMID- 25056918
TI  - Inherent insulin sensitivity is a major determinant of multimeric adiponectin
      responsiveness to short-term weight loss in extreme obesity.
AB  - High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose
      homeostasis better than medium (MMW-A) and low molecular weight (LMW-A)
      components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m(2)),
      we aimed to explore if improvements of multimeric adiponectin following 4-wk
      weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and
      disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers
      were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels
      were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese
      patients, short-term weight loss did not change total adiponectin levels and
      insulin resistance, while the distribution pattern of adiponectin oligomers
      changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A
      (p < 0.05). By multivariate analysis, final HMW-A levels were significantly
      related to baseline ISIOGTT and final body weight (adjusted R(2) = 0.41). Our
      data suggest that HMW adiponectin may reflect baseline insulin sensitivity
      appropriately in the context of extreme obesity. Especially, we documented that
      HMW-A is promptly responsive to short-term weight loss prior to changes in
      insulin resistance, by a magnitude that is proportioned to whole body insulin
      sensitivity. This may suggest an insulin sensitivity-dependent control operated
      by HMW-A on metabolic dynamics of patients with extreme obesity.

PMID- 25056920
TI  - Controversies in the management of advanced melanoma: "gray" areas amid the
      "black and blue".
AB  - OBJECTIVE: To examine the current controversies and discuss consensus
      recommendations regarding treatment sequencing and the role of BRAF inhibitor at
      disease progression. DATA SOURCE: An English-language literature search of
      MEDLINE/PubMed (1966-May 2014), using the keywords advanced melanoma, ipilimumab,
      cytotoxic T-lymphocyte antigen 4, dabrafenib, vemurafenib, BRAF inhibitor,
      trametinib, MEK inhibitor, and treatment sequencing was conducted. Data were also
      obtained from package inserts, meeting abstracts, and clinical registries. STUDY
      SELECTION AND DATA EXTRACTION: All relevant published articles and abstracts on
      ipilimumab, vemurafenib, dabrafenib, and trametinib were reviewed. Clinical trial
      registries and meeting abstracts were used for ongoing studies. DATA SYNTHESIS:
      The availability of new agents has made therapy selection more complex.
      Immunotherapy supporters reason that immunotherapy offers the best chance for
      long-term benefit and does not compromise the antitumor activity of subsequent
      BRAF inhibitors. Targeted therapy advocates rely on the high probability and
      rapid onset of response to BRAF inhibitors. Currently, there is insufficient
      evidence regarding the role of BRAF inhibitor at disease progression.
      CONCLUSIONS: Therapy should be individualized based on patient- and disease
      specific factors. Immunotherapy represents the best option for durable remission;
      however, targeted therapy is more appropriate for patients who are symptomatic or
      have rapidly growing tumors. The novel therapies have also demonstrated
      meaningful intracranial activity; thus, the presence of brain metastases should
      be taken into consideration in selecting therapy. Limited data exist about the
      continuation of BRAF inhibitors after therapeutic failure. Active research is
      ongoing to define the best option for patients with BRAF inhibitor refractory
      disease.

PMID- 25056921
TI  - The reductase activity of the Arabidopsis caleosin RESPONSIVE TO DESSICATION20
      mediates gibberellin-dependent flowering time, abscisic acid sensitivity, and
      tolerance to oxidative stress.
AB  - Contrasting with the wealth of information available on the multiple roles of
      jasmonates in plant development and defense, knowledge about the functions and
      the biosynthesis of hydroxylated oxylipins remains scarce. By expressing the
      caleosin RESPONSIVE TO DESSICATION20 (RD20) in Saccharomyces cerevisiae, we show
      that the recombinant protein possesses an unusual peroxygenase activity with
      restricted specificity toward hydroperoxides of unsaturated fatty acid.
      Accordingly, Arabidopsis (Arabidopsis thaliana) plants overexpressing RD20
      accumulate the product 13-hydroxy-9,11,15-octadecatrienoic acid, a linolenate
      derived hydroxide. These plants exhibit elevated levels of reactive oxygen
      species (ROS) associated with early gibberellin-dependent flowering and abscisic
      acid hypersensitivity at seed germination. These phenotypes are dependent on the
      presence of active RD20, since they are abolished in the rd20 null mutant and in
      lines overexpressing RD20, in which peroxygenase was inactivated by a point
      mutation of a catalytic histidine residue. RD20 also confers tolerance against
      stress induced by Paraquat, Rose Bengal, heavy metal, and the synthetic auxins 1
      naphthaleneacetic acid and 2,4-dichlorophenoxyacetic acid. Under oxidative
      stress, 13-hydroxy-9,11,15-octadecatrienoic acid still accumulates in RD20
      overexpressing lines, but this lipid oxidation is associated with reduced ROS
      levels, minor cell death, and delayed floral transition. A model is discussed
      where the interplay between fatty acid hydroxides generated by RD20 and ROS is
      counteracted by ethylene during development in unstressed environments. 

PMID- 25056922
TI  - Symplastic phloem loading in poplar.
AB  - Sap is driven through phloem sieve tubes by an osmotically generated pressure
      gradient between source and sink tissues. In many plants, source pressure results
      from thermodynamically active loading in which energy is used to transfer sucrose
      (Suc) from mesophyll cells to the phloem of leaf minor veins against a
      concentration gradient. However, in some species, almost all trees, correlative
      evidence suggests that sugar migrates passively through plasmodesmata from
      mesophyll cells into the sieve elements. The possibility of alternate loading
      mechanisms has important ramifications for the regulation of phloem transport and
      source-sink interactions. Here, we provide experimental evidence that, in gray
      poplar (Populus tremula * Populus alba), Suc enters the phloem through
      plasmodesmata. Transgenic plants were generated with yeast invertase in the cell
      walls to prevent Suc loading by this route. The constructs were driven either by
      the constitutive 35S promoter or the minor vein-specific galactinol synthase
      promoter. Transgenic plants grew at the same rate as the wild type without
      symptoms of loading inhibition, such as accumulation of carbohydrates or leaf
      chlorosis. Rates of photosynthesis were normal. In contrast, alfalfa (Medicago
      sativa) plants, which have limited numbers of plasmodesmata between mesophyll and
      phloem, displayed typical symptoms of loading inhibition when transformed with
      the same DNA constructs. The results are consistent with passive loading of Suc
      through plasmodesmata in poplar. We also noted defense-related symptoms in leaves
      of transgenic poplar when the plants were abruptly exposed to excessively high
      temperatures, adding to evidence that hexose is involved in triggering the
      hypersensitive response. 

PMID- 25056923
TI  - Ideal osmotic spaces for chlorobionts or cyanobionts are differentially realized
      by lichenized fungi.
AB  - Lichens result from symbioses between a fungus and either a green alga or a
      cyanobacterium. They are known to exhibit extreme desiccation tolerance. We
      investigated the mechanism that makes photobionts biologically active under
      severe desiccation using green algal lichens (chlorolichens), cyanobacterial
      lichens (cyanolichens), a cephalodia-possessing lichen composed of green algal
      and cyanobacterial parts within the same thallus, a green algal photobiont, an
      aerial green alga, and a terrestrial cyanobacterium. The photosynthetic response
      to dehydration by the cyanolichen was almost the same as that of the terrestrial
      cyanobacterium but was more sensitive than that of the chlorolichen or the
      chlorobiont. Different responses to dehydration were closely related to cellular
      osmolarity; osmolarity was comparable between the cyanolichen and a
      cyanobacterium as well as between a chlorolichen and a green alga. In the
      cephalodium-possessing lichen, osmolarity and the effect of dehydration on
      cephalodia were similar to those exhibited by cyanolichens. The green algal part
      response was similar to those exhibited by chlorolichens. Through the analysis of
      cellular osmolarity, it was clearly shown that photobionts retain their original
      properties as free-living organisms even after lichenization. 

PMID- 25056924
TI  - Thyroglossal duct remnant carcinoma: beyond the Sistrunk procedure.
AB  - Thyroglossal duct remnants (TGDRs) account for more than 70% of anterior neck
      masses in children and 7% in adults; however, cancer is identified in only 1-2%
      of the cases. The diagnosis of a TGDR is based on clinical manifestation of a
      painless, anterior neck swelling, which elevates with swallowing. Cytological
      evaluation with fine needle aspiration and biopsy (FNAB) may facilitate the pre
      operative diagnosis of malignancy, as the majority of TGDR cancers are of
      papillary histotype. The recommended treatment for symptomatic TGDR without
      evidence of malignancy is a Sistrunk procedure, which entails en bloc resection
      of the remnant and the mid-portion of the hyoid bone. The optimal management of
      patients with diagnosed malignancy is controversial, and in the past, additional
      total thyroidectomy was recommended for all of these patients. The purpose of
      this study is to review the literature on TGDR carcinomas, present the evidence
      on the available diagnostic tools, identify the surgical and post-operative
      medical management strategies, discuss current controversies, and conclude with a
      management algorithm. 

PMID- 25056925
TI  - High-throughput bead-based identification of structure-switching aptamer beacons.
AB  - We describe a new platform to identify structure-switching DNA beacon aptamers,
      which detect small molecules in a specific manner. By clonally amplifying a DNA
      library designed to fluoresce in response to binding events onto microbeads,
      aptamer beacons can be selected by stringent fluorescence-assisted sorting. We
      validated this method by isolating known and novel anti-steroid aptamers from two
      separate DNA libraries that were structurally enriched with three-way junctions.
      Importantly, aptamers were retrieved in only a few (three) rounds of selection by
      this approach and did not require further optimization, significantly
      streamlining the process of beacon development. 

PMID- 25056926
TI  - The six conserved serine/threonine sites of REPRESSOR OF ga1-3 protein are
      important for its functionality and stability in gibberellin signaling in
      Arabidopsis.
AB  - MAIN CONCLUSION: Our results provide further insight into the regulation of DELLA
      proteins in Arabidopsis . We clarified that phosphorylation modification of the
      six conserved sites is important for RGA functions and stability. The DELLA
      proteins, important plant growth and development repressors mediate the
      gibberellin (GA) signaling pathway. Although these proteins exhibit
      phosphorylation and de-phosphorylation states at the molecular level, little is
      known regarding the effects of different modifications of DELLA proteins on the
      regulation of their bioactivity and stability at the genetic level. In this
      study, six conserved serine (Ser)/threonine (Thr) sites of REPRESSOR OF ga1-3
      (RGA) were substituted with alanine (RGA6A) or aspartic acid (RGA6D) to mimic the
      states of constitutive de-phosphorylation and phosphorylation, respectively. We
      found that the overexpression of de-phosphomimic RGA in Col-0 plants caused GA
      overdose phenotypes, which were similar to DELLA-deficient mutant. These
      phenotypes were probably attributed to de-phosphomimic RGA, which retained its
      transcriptional activation activity that induces GA biosynthetic genes, but lost
      the transcription repressor function that inhibits GA-responsive genes. Further,
      de-phosphomimic RGA was unstable and easily degradable unlike the wild-type RGA,
      suggesting that the de-phosphorylated form is necessary for its degradation. In
      contrast, phosphomimic RGA overexpression caused GA-deficient phenotypes with non
      degradable RGA. These phenotypes were probably due to phosphomimic RGA, which
      represses GA-responsive gene expression instead of inducing GA biosynthetic
      genes. In addition, phosphomimic RGA was stable and hardly degradable, which
      aggravated the RGA-inhibiting function in GA signaling. In conclusion, we show
      that the six conserved Ser/Thr sites are important for the different
      bioactivities of the RGA protein that regulate the GA response, and also for RGA
      stability via the mimicking of phosphorylation/de-phosphorylation.

PMID- 25056927
TI  - Characterization of two monoterpene synthases involved in floral scent formation
      in Hedychium coronarium.
AB  - Hedychium coronarium, a perennial herb belonging to the family Zingiberaceae, is
      cultivated as a garden plant or cut flower as well as for medicine and aromatic
      oil. Its flowers emit a fresh and inviting scent, which is mainly because of
      monoterpenes present in the profile of the floral volatiles. However, fragrance
      produced as a result of monoterpenes has not been well studied. In the present
      study, two novel terpene synthase (TPS) genes (HcTPS7 and HcTPS8) were isolated
      to study the biosynthesis of monoterpenes in H. coronarium. In vitro
      characterization showed that the recombinant HcTPS7 was capable of generating
      sabinene as its main product, in addition to nine sub-products from geranyl
      diphosphate (GPP). Recombinant HcTPS8 almost specifically catalyzed the formation
      of linalool from GPP, while it converted farnesyl diphosphate (FPP) to alpha
      bergamotene, cis-alpha-bisabolene, beta-farnesene and other ten sesquiterpenes.
      Subcellular localization experiments revealed that HcTPS7 and HcTPS8 were located
      in plastids. Real-time PCR analyses showed that HcTPS7 and HcTPS8 genes were
      highly expressed in petals and sepals, but were almost undetectable in vegetative
      organs. The changes of their expression levels in petals were positively
      correlated with the emission patterns of sabinene and linalool, respectively,
      during flower development. The results indicated that HcTPS7 and HcTPS8 were
      involved in the biosynthesis of sabinene and linalool in H. coronarium flowers.
      Results on these two TPSs first characterized from H. coronarium provide new
      insights into molecular mechanisms of terpene biosynthesis in this species and
      also lay the basis for biotechnological modification of floral scent profile in
      Hedychium.

PMID- 25056928
TI  - S-nitrosylation of Cofilin-1 Serves as a Novel Pathway for VEGF-Stimulated
      Endothelial Cell Migration.
AB  - Nitric oxide (NO) derived from endothelial NO synthase (eNOS) mediates vascular
      endothelial growth factor (VEGF)-stimulated endothelial cytoskeleton remodeling
      and migration; however, the underlying mechanisms are elusive. Covalent adduction
      of a NO moiety (NO(*)) to cysteines called S-nitrosylation (SNO) is a key NO
      signaling pathway. The small actin-binding protein cofilin-1 (CFL1) is essential
      for actin cytoskeleton remodeling. We investigated whether S-nitrosylation
      regulates CFL1 function and endothelial cytoskeleton remodeling and migration
      upon VEGF stimulation. VEGF rapidly stimulated S-nitrosylation of CFL1, which was
      blocked by NO Synthase inhibition and eNOS knockdown by specific eNOS-siRNA.
      Cys80 and Cys139 were identified as the major SNO-sites in CFL1 by LC-MS/MS. The
      actin severing activity of recombinant SNO-mimetic CFL1 (C80/139A DMA-CFL1), but
      not SNO-deficient CFL1 (C80/139S DMS-CFL1), was significantly greater than that
      of wild-type CFL1 (wt-CFL1). When wt-CFL1 and its mutants were overexpressed in
      endothelial cells, basal actin bound wt-CFL1 was undetectable but significantly
      increased by VEGF; basal actin bound DMA-CFL1 was readily high and basal actin
      bound DMS-CFL1 was detectable but low, and both were unresponsive to VEGF.
      Treatment with VEGF significantly increased filamentous (F-) actin and filopodium
      formation and cell migration in endothelial cells. Overexpression of wt-CFL1
      inhibited VEGF-induced F-actin formation. Overexpression of DMA but not DMS CFL1
      decreased basal but not VEGF-stimulated F-actin formation. Overexpression of DMA
      but not DMS CFL1 suppressed VEGF-stimulated filopodium formation and migration in
      endothelial cells. Thus, S-nitrosylation of CFL1 provides a novel signaling
      pathway post-NO biosynthesis via eNOS-derived NO for endothelial cytoskeleton
      remodeling and migration upon VEGF stimulation.

PMID- 25056929
TI  - Folded alkyl chains in water-soluble capsules and cavitands.
AB  - A deep cavitand with ionic "feet" dimerizes around hydrophobic compounds in D2O.
      Longer n-alkane guests, C14-C18, are encapsulated in contorted conformations and
      NMR is used to deduce their shapes. Competition experiments establish the driving
      forces involved and how they compensate for the steric clashes in the folded
      structures of the encapsulated alkanes. Bolaamphiphiles instead prefer to bind in
      the monomeric cavitand with conformations that bury the methylenes but expose the
      polar head groups to solvent. 

PMID- 25056930
TI  - A generalizable DNA-catalyzed approach to peptide-nucleic acid conjugation.
AB  - We report DNA catalysts (deoxyribozymes) that join tyrosine-containing peptides
      to RNA and DNA in one step and without requiring protecting groups on either the
      peptide or the nucleic acid. Our previous efforts towards this goal required
      tethering the peptide to a DNA anchor oligonucleotide. Here, we established
      direct in vitro selection for deoxyribozymes that use untethered, free peptide
      substrates. This approach enables imposition of selection pressure via reduced
      peptide concentration and leads to preparatively useful lower apparent Km values
      of ~100 MUM peptide. Use of phosphorimidazolide (Imp) rather than triphosphate as
      the electrophile enables reactivity of either terminus (5' or 3') of both RNA and
      DNA. Our findings establish a generalizable means of joining unprotected peptide
      to nucleic acid in one step by using DNA catalysts identified by in vitro
      selection. 

PMID- 25056932
TI  - Magnified effects of the COMT gene on white-matter microstructure in very old
      age.
AB  - Genetic factors may partly account for between-person differences in brain
      integrity in old age. Evidence from human and animal studies suggests that the
      dopaminergic system is implicated in the modulation of white-matter integrity. We
      investigated whether a genetic variation in the Catechol-O-Methyltransferase
      (COMT) Val158Met polymorphism, which influences dopamine availability in
      prefrontal cortex, contributes to interindividual differences in white-matter
      microstructure, as measured with diffusion-tensor imaging. In a sample of older
      adults from a population-based study (60-87 years; n = 238), we found that the
      COMT polymorphism affects white-matter microstructure, indexed by fractional
      anisotropy and mean diffusivity, of several white-matter tracts in the oldest age
      group (81-87 years), although there were no reliable associations between COMT
      and white-matter microstructure in the two younger age groups (60-66 and 72-78
      years). These findings extend previous observations of magnified genetic effects
      on cognition in old age to white-matter integrity.

PMID- 25056931
TI  - Spatial distribution of neurons innervated by chandelier cells.
AB  - Chandelier (or axo-axonic) cells are a distinct group of GABAergic interneurons
      that innervate the axon initial segments of pyramidal cells and are thus thought
      to have an important role in controlling the activity of cortical circuits. To
      examine the circuit connectivity of chandelier cells (ChCs), we made use of a
      genetic targeting strategy to label neocortical ChCs in upper layers of juvenile
      mouse neocortex. We filled individual ChCs with biocytin in living brain slices
      and reconstructed their axonal arbors from serial semi-thin sections. We also
      reconstructed the cell somata of pyramidal neurons that were located inside the
      ChC axonal trees and determined the percentage of pyramidal neurons whose axon
      initial segments were innervated by ChC terminals. We found that the total
      percentage of pyramidal neurons that were innervated by a single labeled ChC was
      18-22 %. Sholl analysis showed that this percentage peaked at 22-35 % for
      distances between 30 and 60 um from the ChC soma, decreasing to lower percentages
      with increasing distances. We also studied the three-dimensional spatial
      distribution of the innervated neurons inside the ChC axonal arbor using spatial
      statistical analysis tools. We found that innervated pyramidal neurons are not
      distributed at random, but show a clustered distribution, with pockets where
      almost all cells are innervated and other regions within the ChC axonal tree that
      receive little or no innervation. Thus, individual ChCs may exert a strong,
      widespread influence on their local pyramidal neighbors in a spatially
      heterogeneous fashion.

PMID- 25056933
TI  - Multiscale fingerprinting of neuronal functional connectivity.
AB  - Current cellular-based connectomics approaches aim to delineate the functional or
      structural organizations of mammalian brain circuits through neuronal activity
      mapping and/or axonal tracing. To discern possible connectivity between
      functionally identified neurons in widely distributed brain circuits, reliable
      and efficient network-based approaches of cross-registering or cross-correlating
      such functional-structural data are essential. Here, a novel cross-correlation
      approach that exploits multiple timing-specific, response-specific, and cell
      specific neuronal characteristics as coincident fingerprint markers at the
      systems, network, and cellular levels is proposed. Application of this multiscale
      temporal-cellular coincident fingerprinting assay to the respiratory central
      pattern generator network in rats revealed a descending excitatory pathway with
      characteristic activity pattern and projecting from a distinct neuronal
      population in pons to its counterparts in medulla that control the post
      inspiratory phase of the respiratory rhythm important for normal breathing,
      airway protection, and respiratory-vocalization coordination. This enabling
      neurotracing approach may prove valuable for functional connectivity mapping of
      other brain circuits. 

PMID- 25056934
TI  - 2013 clinical practice guidelines (The Japanese Breast Cancer Society): history,
      policy and mission.

PMID- 25056935
TI  - Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome
      provides insight into falciparum-specific cell biology.
AB  - One of the critical gaps in malaria transmission biology and surveillance is our
      lack of knowledge about Plasmodium falciparum gametocyte biology, especially
      sexual dimorphic development and how sex ratios that may influence transmission
      from the human to the mosquito. Dissecting this process has been hampered by the
      lack of sex-specific protein markers for the circulating, mature stage V
      gametocytes. The current evidence suggests a high degree of conservation in
      gametocyte gene complement across Plasmodium, and therefore presumably for sex
      specific genes as well. To better our understanding of gametocyte development and
      subsequent infectiousness to mosquitoes, we undertook a Systematic Subtractive
      Bioinformatic analysis (filtering) approach to identify sex-specific P.
      falciparum NF54 protein markers based on a comparison with the Dd2 strain, which
      is defective in producing males, and with syntenic male and female proteins from
      the reanalyzed and updated P. berghei (related rodent malaria parasite)
      gametocyte proteomes. This produced a short list of 174 male- and 258 female
      enriched P. falciparum stage V proteins, some of which appear to be under strong
      diversifying selection, suggesting ongoing adaptation to mosquito vector species.
      We generated antibodies against three putative female-specific gametocyte stage V
      proteins in P. falciparum and confirmed either conserved sex-specificity or the
      lack of cross-species sex-partitioning. Finally, our study provides not only an
      additional resource for mass spectrometry-derived evidence for gametocyte
      proteins but also lays down the foundation for rational screening and development
      of novel sex-partitioned protein biomarkers and transmission-blocking vaccine
      candidates. 

PMID- 25056936
TI  - A systematic proteomic analysis of Listeria monocytogenes house-keeping protein
      secretion systems.
AB  - Listeria monocytogenes is a firmicute bacterium causing serious infections in
      humans upon consumption of contaminated food. Most of its virulence factors are
      secretory proteins either released to the medium or attached to the bacterial
      surface. L. monocytogenes encodes at least six different protein secretion
      pathways. Although great efforts have been made in the past to predict secretory
      proteins and their secretion routes using bioinformatics, experimental evidence
      is lacking for most secretion systems. Therefore, we constructed mutants in the
      main housekeeping protein secretion systems, which are the Sec-dependent
      transport, the YidC membrane insertases SpoIIIJ and YqjG, as well as the twin
      arginine pathway, and analyzed their secretion and virulence defects. Our results
      demonstrate that Sec-dependent secretion and membrane insertion of proteins via
      YidC proteins are essential for viability of L. monocytogenes. Depletion of SecA
      or YidC activity severely affected protein secretion, whereas loss of the Tat
      pathway was without any effect on secretion, viability, and virulence. Two
      dimensional gel electrophoresis combined with protein identification by mass
      spectrometry revealed that secretion of many virulence factors and of enzymes
      synthesizing and degrading the cell wall depends on the SecA route. This finding
      was confirmed by SecA inhibition experiments using sodium azide. Analysis of
      secretion of substrates typically dependent on the accessory SecA2 ATPase in wild
      type and azide resistant mutants of L. monocytogenes revealed for the first time
      that SecA2-dependent protein secretion also requires the ATPase activity of the
      house-keeping SecA protein. 

PMID- 25056937
TI  - Inhibition of circulating dipeptidyl peptidase 4 activity in patients with
      metastatic prostate cancer.
AB  - Cancer is responsible for many deaths and is a major source of healthcare
      expenditures. The identification of new, non-invasive biomarkers might allow
      improvement of the direct diagnostic or prognostic ability of already available
      tools. Here, we took the innovative approach of interrogating the activity of
      exopeptidases in the serum of cancer patients with the aim of establishing a
      distinction based on enzymatic function, instead of simple protein levels, as a
      means to biomarker discovery. We first analyzed two well-characterized mouse
      models of prostate cancer, each with a distinct genetic lesion, and established
      that broad exopeptidase and targeted aminopeptidase activity tests reveal
      proteolytic changes associated with tumor development. We also describe new
      peptide-based freeze-frame reagents uniquely suited to probe the altered balance
      of selected aminopeptidases, as opposed to the full array of exopeptidases,
      and/or their modulators in patient serum or plasma. One particular proteolytic
      activity was impaired in animals with aggressive disease relative to cancer-free
      littermates. We identified the protease in question as dipeptidyl peptidase 4
      (DPP4) by analyzing selected knockout mice and evaluating the effect of specific
      inhibitors. DPP4 activity was also reduced in the sera of patients with
      metastatic prostate cancer relative to patients with localized disease or healthy
      controls. However, no significant differences in DPP4 serum levels were observed,
      which established the loss of activity as the result of impaired enzymatic
      function. Biochemical analysis indicated that reduced activity was the result not
      of post-translational modifications or allosteric changes, but instead of a low
      molecular-weight inhibitor. After we adjusted for age and total prostate-specific
      antigen, reduced DPP4 activity remained a significant predictor of cancer status.
      The results of this proof-of-principle study suggest that DPP4 activity might be
      a potential blood-based indicator of the presence of metastatic cancer of
      prostatic origin, either by itself or, more likely, as a means to improve the
      sensitivity and specificity of existing markers. 

PMID- 25056938
TI  - Broad-range glycosidase activity profiling.
AB  - Plants produce hundreds of glycosidases. Despite their importance in cell wall
      (re)modeling, protein and lipid modification, and metabolite conversion, very
      little is known of this large class of glycolytic enzymes, partly because of
      their post-translational regulation and their elusive substrates. Here, we
      applied activity-based glycosidase profiling using cell-permeable small molecular
      probes that react covalently with the active site nucleophile of retaining
      glycosidases in an activity-dependent manner. Using mass spectrometry we detected
      the active state of dozens of myrosinases, glucosidases, xylosidases, and
      galactosidases representing seven different retaining glycosidase families. The
      method is simple and applicable for different organs and different plant species,
      in living cells and in subproteomes. We display the active state of previously
      uncharacterized glycosidases, one of which was encoded by a previously declared
      pseudogene. Interestingly, glycosidase activity profiling also revealed the
      active state of a diverse range of putative xylosidases, galactosidases,
      glucanases, and heparanase in the cell wall of Nicotiana benthamiana. Our data
      illustrate that this powerful approach displays a new and important layer of
      functional proteomic information on the active state of glycosidases. 

PMID- 25056939
TI  - Illness perceptions in relation to experiences of contemporary cancer care
      settings among colorectal cancer survivors and their partners.
AB  - Illness is constituted by subjective experiences of symptoms and their
      psychosocial consequences. Illness perceptions concern people's lay beliefs about
      understandings and interpretation of a disease and expectations as to disease
      outcome. Our knowledge about illness perceptions and coping in relation to the
      cancer care context among persons with colorectal cancer (CRC) and their partners
      is incomplete. The aim of the present study was to explore illness perceptions in
      relation to contemporary cancer care settings among CRC survivors and partners.
      The present research focused on illness rather than disease, implying that
      personal experiences are central to the methodology. The grounded theory method
      used is that presented by Kathy Charmaz. The present results explore illness
      perceptions in the early recovery phase after being diagnosed and treated for
      cancer in a contemporary cancer care setting. The core category outlook on the
      cancer diagnosis when quickly informed, treated, and discharged illustrates the
      illness perceptions of survivors and partners as well as the environment in which
      they were found. The cancer care environment is presented in the conceptual
      category experiencing contemporary cancer care settings. Receiving treatment
      quickly and without waiting was a positive experience for both partners and
      survivors; however partners experienced the information as massive and as causing
      concern. The period after discharge was being marked by uncertainty and
      loneliness, and partners tended to experience non-continuity in care as more
      problematic than the survivor did. The results showed different illness
      perceptions and a mismatch between illness perceptions among survivors and
      partners, presented in the conceptual category outlook on the cancer diagnosis.
      One illness perception, here presented among partners, focused on seeing the
      cancer diagnosis as a permanent life-changing event. The other illness
      perception, here presented among survivors, concentrated on leaving the cancer
      diagnosis behind and moving forward. The importance of illness perceptions among
      survivors, and the differences in illness perceptions between survivors and
      partners, should be recognized by healthcare professionals to achieve the goals
      of person-centered contemporary cancer care. 

PMID- 25056940
TI  - Epidemiology of hookworm (Uncinaria sanguinis) infection in free-ranging
      Australian sea lion (Neophoca cinerea) pups.
AB  - Understanding the fundamental factors influencing the epidemiology of wildlife
      disease is essential to determining the impact of disease on individual health
      and population dynamics. The host-pathogen-environment relationship of the
      endangered Australian sea lion (Neophoca cinerea) and the parasitic hookworm,
      Uncinaria sanguinis, was investigated in neonatal pups during summer and winter
      breeding seasons at two biogeographically disparate colonies in South Australia.
      The endemic occurrence of hookworm infection in Australian sea lion pups at these
      sites was 100% and post-parturient transmammary transmission is likely the
      predominant route of hookworm infection for pups. The prepatent period for U.
      sanguinis in Australian sea lion pups was determined to be 11-14 days and the
      duration of infection approximately 2-3 months. The mean hookworm infection
      intensity in pups found dead was 2138 +/- 552 (n = 86), but a significant
      relationship between infection intensity and faecal egg count was not identified;
      infection intensity in live pups could not be estimated from faecal samples.
      Fluctuations in infection intensity corresponded to oscillations in the magnitude
      of colony pup mortality, that is, higher infection intensity was significantly
      associated with higher colony pup mortality and reduced pup body condition. The
      dynamic interaction between colony, season, and host behaviour is hypothesised to
      modulate hookworm infection intensity in this species. This study provides a new
      perspective to understanding the dynamics of otariid hookworm infection and
      provides evidence that U. sanguinis is a significant agent of disease in
      Australian sea lion pups and could play a role in population regulation in this
      species.

PMID- 25056941
TI  - Distribution and genetic structure of Aedes japonicus japonicus populations
      (Diptera: Culicidae) in Germany.
AB  - In recent years, the number of imported cases of arthropod-borne diseases in
      Europe, such as dengue fever, has increased steadily, as did the emergence and
      distribution of invasive insect vectors. Consequently, the risk of disease
      spreading into previously unaffected regions through invasive mosquitoes is also
      increasing. One example of an invasive mosquito is Aedes japonicus japonicus (A.
      j. japonicus), which spread from its original habitat in Japan to North America
      and Europe. This species has been shown to act as a vector for Japanese
      encephalitis and West Nile viruses. In Europe, A. j. japonicus has been detected
      in Switzerland, Belgium, Slovenia, and Germany, where it has become a resident
      species. Here, we describe the recent spread and genetic structure of A. j.
      japonicus populations in Germany. By monitoring the species in Baden-Wurttemberg
      in 2011 and 2012, we observed a considerable enlargement of the infested area
      from 54 municipalities in 2011 to 124 municipalities in 2012. To elucidate the
      colonization of Europe by A. j. japonicus, seven microsatellite loci were studied
      in 106 individuals sampled in Germany and Switzerland in 2012. The same markers
      were genotyped in 31 North American and 26 Japanese specimens. Population genetic
      analyses indicated that A. j. japonicus in Baden-Wurttemberg and North Rhine
      Westphalia represented two genetically distinct populations with FST-values of
      0.073-0.152, suggesting that they originated from two independent introduction
      events in the past. These results are of particular interest in light of
      vectorial variability for the transmission of viruses and other pathogens in
      Europe. 

PMID- 25056943
TI  - Testosterone persistently dysregulates hepatic expression of Tlr6 and Tlr8
      induced by Plasmodium chabaudi malaria.
AB  - Testosterone (T) is known to induce persistent susceptibility to Plasmodium
      chabaudi malaria. Pathogens recognizing Toll-like receptors (TLRs), though
      potentially important against malaria, have not yet been examined for their T
      sensitivity. Here, we investigate effects of T and P. chabaudi on mRNA expression
      and promoter DNA methylation of Tlr1-9 genes in the liver of female C57BL/6 mice.
      These are treated with T or vehicle for 3 weeks, and then treatment is
      discontinued for 12 weeks, before challenging with P. chabaudi for 8 days. Our
      data reveal that T induces a 9.1-fold downregulation of Tlr6 mRNA and 6.3-fold
      upregulation of Tlr8 mRNA. Blood-stage infections induce significant increases in
      mRNA expression of Tlr1, 2, 4, 6, 7, and 8 varying between 2.5-fold and 21-fold
      in control mice. In T-pretreated mice, these Tlr genes are also significantly
      responsive to infections. However, the malaria-induced upregulations of the
      relative mRNA expressions of Tlr6 and Tlr8 are 5.6-fold higher and 6.5-fold lower
      in T-pretreated mice than in control mice. Infections induce a massive DNA down
      methylation of the Tlr6 gene promoter in control mice, which is still more
      pronounced in T-pretreated mice, while significant changes are not detectable for
      the DNA methylation status of the Tlr8 promoter. Our data support the view that
      hepatic expression of Tlr6, but not that of Tlr8 is epigenetically controlled,
      and that the dysregulations of Tlr6 and Tlr8 critically contribute to T-induced
      persistent susceptibility to P. chabaudi malaria, possibly by dys-balancing
      responses of TLR6-mediated pathogen recognition and TLR8-mediated generation of
      anti-malaria "protective" autoimmunity.

PMID- 25056942
TI  - Evaluation of seed extracts from plants found in the Caatinga biome for the
      control of Aedes aegypti.
AB  - Dengue fever, currently the most important arbovirus, is transmitted by the bite
      of the Aedes aegypti mosquito. Given the absence of a prophylactic vaccine, the
      disease can only be controlled by combating the vector insect. However,
      increasing reports of resistance and environmental damage caused by insecticides
      have led to the urgent search for new safer alternatives. In this regard, plants
      stand out as a source of easy-to-obtain biodegradable insecticide molecules.
      Twenty (20) plant seed extracts from the Caatinga, an exclusively Brazilian
      biome, were prepared. Sodium phosphate (50 mM, pH 8.0) was used as extractor. The
      extracts were used in bioassays and submitted to partial characterisation. A
      Probit analysis of insecticides was carried out, and intergroup differences were
      verified by the Student's t test and ANOVA. All the extracts exhibited larvicidal
      and ovipositional deterrence activity. The extracts of Amburana cearenses,
      Piptadenia viridiflora, Erythrina velutina, Myracrodruon urundeuva and Schinopsis
      brasiliensis were also pupicides, while the extracts of P. viridiflora, E.
      velutina, A. cearenses, Anadenanthera colubrina, Diocleia grandiflora, Bauhinia
      cheilantha, Senna spectabilis, Caesalpinia pyramidalis, Mimosa regnelli and
      Genipa americana displayed adulticidal activity. Egg laying was compromised when
      females were fed extracts of Ricinus communis, Croton sonderianus and S.
      brasiliensis. At least two proteins with insecticidal activity were found in all
      the extracts. Phenol compounds were identified in all the extracts and
      flavonoids, triterpenes or alkaloids in 14 of them. The results show the
      potential of plant seed extracts from the Caatinga as a source of active
      molecules against A. aegypti mosquitos.

PMID- 25056944
TI  - Echinococcus spp. in central Kenya: a different story.
AB  - Research on cystic echinococcosis (CE) has a long history in Kenya, but has
      mainly concentrated on two discrete areas, Turkana and Maasailand, which are
      known to be foci of human CE in Africa. Here, we report on a survey for CE in
      livestock from central to northeastern Kenya, from where no previous data are
      available. A total of 7,831 livestock carcasses were surveyed. CE prevalence was
      1.92% in cattle (n = 4,595), 6.94% in camels (n = 216), 0.37% in goats (n =
      2,955) and 4.62% in sheep (n = 65). Identification of the parasite was done using
      an RFLP-PCR of the mitochondrial nad1 gene, which had been validated before
      against the various Echinococcus taxa currently recognized as distinct species.
      From a total of 284 recovered cysts, 258 could be identified as Echinococcus
      granulosus sensu stricto (n = 160), E. ortleppi (n = 51) and E. canadensis (n =
      47) by RFLP-PCR of nad1. In cattle, fertile cysts occurred mostly in the lungs
      and belonged to E. ortleppi (31 of 54), while the vast majority were sterile or
      calcified cysts of E. granulosus s.s.. Most fertile cysts in camels belonged to
      E. canadensis (33 of 37); sterile or calcified cysts were rare. Goats harboured
      fertile cysts of E. ortleppi (n = 3)--which is the first record in that host
      species--and E. canadensis (n = 1), while all cysts of E. granulosus were
      sterile. Only sterile cysts were found in the three examined sheep. Typically,
      all cysts in animals with multiple infections belonged to the same species, while
      mixed infections were rare. Our data indicate that the epidemiological situation
      in central to northeastern Kenya is clearly different from the well-studied
      pastoral regions of Turkana and Maasailand, and the apparently low number of
      human CE cases correlates with the infrequent occurrence of E. granulosus s.s.

PMID- 25056949
TI  - Polyubiquitinated tristetraprolin protects from TNF-induced, caspase-mediated
      apoptosis.
AB  - Binding of TNF to its receptor (TNFR1) elicits the spatiotemporal assembly of two
      signaling complexes that coordinate the balance between cell survival and cell
      death. We have shown previously that, following TNF treatment, the mRNA decay
      protein tristetraprolin (TTP) is Lys-63-polyubiquitinated by TNF receptor
      associated factor 2 (TRAF2), suggesting a regulatory role in TNFR signaling. Here
      we demonstrate that TTP interacts with TNFR1 in a TRAF2-dependent manner, thereby
      initiating the MEKK1/MKK4-dependent activation of JNK activities. This regulatory
      function toward JNK activation but not NF-kappaB activation depends on lysine 105
      of TTP, which we identified as the corresponding TRAF2 ubiquitination site.
      Disabling TTP polyubiquitination results in enhanced TNF-induced apoptosis in
      cervical cancer cells. Together, we uncover a novel aspect of TNFR1 signaling
      where TTP, in alliance with TRAF2, acts as a balancer of JNK-mediated cell
      survival versus death. 

PMID- 25056950
TI  - Biochemical and structural insights into microtubule perturbation by CopN from
      Chlamydia pneumoniae.
AB  - Although the actin network is commonly hijacked by pathogens, there are few
      reports of parasites targeting microtubules. The proposed member of the LcrE
      protein family from some Chlamydia species (e.g. pCopN from C. pneumoniae) binds
      tubulin and inhibits microtubule assembly in vitro. From the pCopN structure and
      its similarity with that of MxiC from Shigella, we definitively confirm CopN as
      the Chlamydia homolog of the LcrE family of bacterial proteins involved in the
      regulation of type III secretion. We have also investigated the molecular basis
      for the pCopN effect on microtubules. We show that pCopN delays microtubule
      nucleation and acts as a pure tubulin-sequestering protein at steady state. It
      targets the beta subunit interface involved in the tubulin longitudinal self
      association in a way that inhibits nucleotide exchange. pCopN contains three
      repetitions of a helical motif flanked by disordered N- and C-terminal
      extensions. We have identified the pCopN minimal tubulin-binding region within
      the second and third repeats. Together with the intriguing observation that C.
      trachomatis CopN does not bind tubulin, our data support the notion that, in
      addition to the shared function of type III secretion regulation, these proteins
      have evolved different functions in the host cytosol. Our results provide a
      mechanistic framework for understanding the C. pneumoniae CopN-specific
      inhibition of microtubule assembly. 

PMID- 25056951
TI  - Synergistic regulation of glutamatergic transmission by serotonin and
      norepinephrine reuptake inhibitors in prefrontal cortical neurons.
AB  - The monoamine system in the prefrontal cortex has been implicated in various
      mental disorders and has been the major target of anxiolytics and
      antidepressants. Clinical studies show that serotonin and norepinephrine reuptake
      inhibitors (SNRIs) produce better therapeutic effects than single selective
      reuptake inhibitors, but the underlying mechanisms are largely unknown. Here, we
      found that low dose SNRIs, by acting on 5-HT(1A) and alpha2-adrenergic receptors,
      synergistically reduced AMPA receptor (AMPAR)-mediated excitatory postsynaptic
      currents and AMPAR surface expression in prefrontal cortex pyramidal neurons via
      a mechanism involving Rab5/dynamin-mediated endocytosis of AMPARs. The
      synergistic effect of SNRIs on AMPARs was blocked by inhibition of activator of G
      protein signaling 3, a G protein modulator that prevents reassociation of G(i)
      protein alpha subunit and prolongs the betagamma-mediated signaling pathway.
      Moreover, the depression of AMPAR-mediated excitatory postsynaptic currents by
      SNRIs required p38 kinase activity, which was increased by 5-HT(1A) and alpha2
      adrenergic receptor co-activation in an activator of G protein signaling 3
      dependent manner. These results have revealed a potential mechanism for the
      synergy between the serotonin and norepinephrine systems in the regulation of
      glutamatergic transmission in cortical neurons.

PMID- 25056952
TI  - Paradigms of sulfotransferase catalysis: the mechanism of SULT2A1.
AB  - Human cytosolic sulfotransferases (SULTs) regulate the activities of thousands of
      signaling small molecules via transfer of the sulfuryl moiety (-SO3) from 3'
      phosphoadenosine 5'-phosphosulfate (PAPS) to the hydroxyls and primary amines of
      acceptors. Sulfonation controls the affinities of ligands for their targets, and
      thereby regulates numerous receptors, which, in turn, regulate complex cellular
      responses. Despite their biological and medical relevance, basic SULT mechanism
      issues remain unresolved. To settle these issues, and to create an in-depth model
      of SULT catalysis, the complete kinetic mechanism of a representative member of
      the human SULT family, SULT2A1, was determined. The mechanism is composed of
      eight enzyme forms that interconvert via 22 rate constants, each of which was
      determined independently. The result is a complete quantitative description of
      the mechanism that accurately predicts complex enzymatic behavior. This is the
      first description of a SULT mechanism at this resolution, and it reveals numerous
      principles of SULT catalysis and resolves previously ambiguous issues. The
      structures and catalytic behaviors SULTs are highly conserved; hence, the
      mechanism presented here should prove paradigmatic for the family. 

PMID- 25056953
TI  - The duplicated alpha7 subunits assemble and form functional nicotinic receptors
      with the full-length alpha7.
AB  - The alpha7 nicotinic acetylcholine receptor gene (CHRNA7) is linked to
      schizophrenia. A partial duplication of CHRNA7 (CHRFAM7A) is found in humans on
      15q13-14. Exon 6 of CHRFAM7A harbors a 2-bp deletion polymorphism,
      CHRFAM7ADelta2bp, which is also associated with schizophrenia. To understand the
      effects of the duplicated subunits on alpha7 receptors, we fused alpha7,
      dupalpha7, and dupDeltaalpha7 subunits with various fluorescent proteins. The
      duplicated subunits co-localized with full-length alpha7 subunits in mouse
      neuroblastoma cells (Neuro2a) as well as rat hippocampal neurons. We investigated
      the interaction between the duplicated subunits and full-length alpha7 by
      measuring Forster resonance energy transfer using donor recovery after
      photobleaching and fluorescence lifetime imaging microscopy. The results revealed
      that the duplicated proteins co-assemble with alpha7. In electrophysiological
      studies, Leu at the 9'-position in the M2 membrane-spanning segment was replaced
      with Cys in dupalpha7 or dupDeltaalpha7, and constructs were co-transfected with
      full-length alpha7 in Neuro2a cells. Exposure to ethylammonium
      methanethiosulfonate inhibited acetylcholine-induced currents, showing that the
      assembled functional nicotinic acetylcholine receptors (nAChRs) included the
      duplicated subunit. Incorporation of dupalpha7 and dupDeltaalpha7 subunits
      modestly changes the sensitivity of receptors to choline and varenicline. Thus,
      the duplicated proteins are assembled and transported to the cell membrane
      together with full-length alpha7 subunits and alter the function of the nAChRs.
      The characterization of dupalpha7 and dupDeltaalpha7 as well as their influence
      on alpha7 nAChRs may help explain the pathophysiology of schizophrenia and may
      suggest therapeutic strategies. 

PMID- 25056954
TI  - Binding of TPP1 protein to TIN2 protein is required for POT1a,b protein-mediated
      telomere protection.
AB  - The single-stranded DNA binding proteins in mouse shelterin, POT1a and POT1b,
      accumulate at telomeres as heterodimers with TPP1, which binds TIN2 and thus
      links the TPP1/POT1 dimers with TRF1 and TRF2/Rap1. When TPP1 is tethered to
      TIN2/TRF1/TRF2, POT1a is thought to block replication protein A binding to the
      single-stranded telomeric DNA and prevent ataxia telangiectasia and Rad3-related
      kinase activation. Similarly, TPP1/POT1b tethered to TIN2 can control the
      formation of the correct single-stranded telomeric overhang. Consistent with this
      view, the telomeric phenotypes following deletion of POT1a,b or TPP1 are
      phenocopied in TIN2-deficient cells. However, the loading of TRF1 and TRF2/Rap1
      is additionally compromised in TIN2 KO cells, leading to added phenotypes.
      Therefore, it could not be excluded that, in addition to TIN2, other components
      of shelterin contribute to the recruitment of TPP1/POT1a,b as suggested by
      previous reports. To test whether TIN2 is the sole link between TPP1/POT1a,b and
      telomeres, we defined the TPP1 interaction domain of TIN2 and generated a TIN2
      allele that was unable to interact with TPP1 but retained its interaction with
      TRF1 and TRF2. We demonstrated that cells expressing TIN2DeltaTPP1 instead of
      wild-type TIN2 phenocopy the POT1a,b knockout setting without showing additional
      phenotypes. Therefore, these results are consistent with TIN2 being the only
      mechanism by which TPP1/POT1 heterodimers bind to shelterin and function in
      telomere protection. 

PMID- 25056955
TI  - Molecular mechanisms for sweet-suppressing effect of gymnemic acids.
AB  - Gymnemic acids are triterpene glycosides that selectively suppress taste
      responses to various sweet substances in humans but not in mice. This sweet
      suppressing effect of gymnemic acids is diminished by rinsing the tongue with
      gamma-cyclodextrin (gamma-CD). However, little is known about the molecular
      mechanisms underlying the sweet-suppressing effect of gymnemic acids and the
      interaction between gymnemic acids versus sweet taste receptor and/or gamma-CD.
      To investigate whether gymnemic acids directly interact with human (h) sweet
      receptor hT1R2 + hT1R3, we used the sweet receptor T1R2 + T1R3 assay in
      transiently transfected HEK293 cells. Similar to previous studies in humans and
      mice, gymnemic acids (100 MUg/ml) inhibited the [Ca(2+)]i responses to sweet
      compounds in HEK293 cells heterologously expressing hT1R2 + hT1R3 but not in
      those expressing the mouse (m) sweet receptor mT1R2 + mT1R3. The effect of
      gymnemic acids rapidly disappeared after rinsing the HEK293 cells with gamma-CD.
      Using mixed species pairings of human and mouse sweet receptor subunits and
      chimeras, we determined that the transmembrane domain of hT1R3 was mainly
      required for the sweet-suppressing effect of gymnemic acids. Directed mutagenesis
      in the transmembrane domain of hT1R3 revealed that the interaction site for
      gymnemic acids shared the amino acid residues that determined the sensitivity to
      another sweet antagonist, lactisole. Glucuronic acid, which is the common
      structure of gymnemic acids, also reduced sensitivity to sweet compounds. In our
      models, gymnemic acids were predicted to dock to a binding pocket within the
      transmembrane domain of hT1R3. 

PMID- 25056957
TI  - Progranulin transcripts with short and long 5' untranslated regions (UTRs) are
      differentially expressed via posttranscriptional and translational repression.
AB  - Frontotemporal lobar degeneration is associated with cytoplasmic or nuclear
      deposition of the TAR DNA-binding protein 43 (TDP-43). Haploinsufficiency of
      progranulin (GRN) is a major genetic risk factor for frontotemporal lobar
      degeneration associated with TDP-43 deposition. Therefore, understanding the
      mechanisms that control cellular expression of GRN is required not only to
      understand disease etiology but also for the development of potential therapeutic
      strategies. We identified different GRN transcripts with short (38-93
      nucleotides) or long (219 nucleotides) 5' UTRs and demonstrate a cellular
      mechanism that represses translation of GRN mRNAs with long 5' UTRs. The long 5'
      UTR of GRN mRNA contains an upstream open reading frame (uORF) that is absent in
      all shorter transcripts. Because such UTRs can be involved in translational
      control as well as in mRNA stability, we compared the expression of GRN in cells
      expressing cDNAs with and without 5' UTRs. This revealed a selective repression
      of GRN translation and a reduction of mRNA levels by the 219-nucleotide-long 5'
      UTR. The specific ability of this GRN 5' UTR to repress protein expression was
      further confirmed by its transfer to an independent reporter. Deletion analysis
      identified a short stretch between nucleotides 76 and 125 containing two start
      codons within one uORF that is required and sufficient for repression of protein
      expression. Mutagenesis of the two AUG codons within the uORF is sufficient to
      reduce translational repression. Therefore initiating ribosomes at the AUGs of
      the uORF fail to efficiently initiate translation at the start codon of GRN. In
      parallel the 5' UTR also affects mRNA stability; thus two independent mechanisms
      determine GRN expression via mRNA stability and translational efficiency. 

PMID- 25056959
TI  - Atomic mechanism of predictable phase transition in dual-phase H2 Ti3 O7 /TiO2
      (B) nanofiber: an in situ heating TEM investigation.
AB  - The phase transition from H(2)Ti(3)O(7) to TiO(2) (B) in a 1D single nanocrystal
      of H(2)Ti(3)O(7) was observed by in situ heating in a transmission electron
      microscope experimentally. The results indicate a typical monoclinic-to
      monoclinic crystallographic orientation relationship between the two phases.
      Moreover, the fundamental building blocks and invariant deformation element model
      were both adopted to reveal the atomic mechanism and predict the crystallographic
      orientation relationship quantitatively for the phase transition. The prediction
      was precisely consistent with TEM results.

PMID- 25056958
TI  - N-terminal pro-C-natriuretic peptide and cytokine kinetics in dogs with
      endotoxemia.
AB  - BACKGROUND: Serum N-terminal pro-C-natriuretic peptide (NT-proCNP) concentration
      at hospital admission has sufficient sensitivity and specificity to differentiate
      naturally occurring sepsis from nonseptic systemic inflammatory response syndrome
      (SIRS). However, little is known about serum NT-proCNP concentrations in dogs
      during the course of sepsis. OBJECTIVE: To determine serum NT-proCNP and cytokine
      kinetics in dogs with endotoxemia, a model of canine sepsis. SAMPLES: Eighty
      canine serum samples. METHODS: Eight healthy adult Beagles were randomized to
      receive Escherichia coli lipopolysaccharide (LPS, 5 MUg/kg) or placebo (0.9%
      NaCl) as a single IV dose in a randomized crossover study. Serum collected at 0,
      1, 2, 4, and 24 hours was stored at -80 degrees C for batch analysis. Serum NT
      proCNP was measured by ELISA and 13 cytokines and chemokines by multiplex
      magnetic bead-based assay. RESULTS: Serum NT-proCNP concentrations did not differ
      significantly between LPS- and placebo-treated dogs at any time. When comparing
      serum cytokine concentrations, LPS-treated dogs had higher interleukin-6 (IL-6),
      IL-10, TNF-alpha and KC-like at 1, 2, and 4 hours; higher CCL2 at 1, 2, 4, and 24
      hours; and higher IL-8 and CXCL10 at 4 hours compared to placebo-treated dogs.
      There were no differences in serum GM-CSF, IFN-gamma, IL-2, IL-7, IL-15 or IL-18
      between LPS- and placebo-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum
      NT-proCNP concentration does not change significantly in response to LPS
      administration in healthy dogs. Certain serum cytokine and chemokine
      concentrations are significantly increased within 1-4 hours after LPS
      administration and warrant further investigation as tools for the detection and
      management of sepsis in dogs.

PMID- 25056956
TI  - Arachidonic acid induces direct interaction of the p67(phox)-Rac complex with the
      phagocyte oxidase Nox2, leading to superoxide production.
AB  - The phagocyte NADPH oxidase Nox2, heterodimerized with p22(phox) in the membrane,
      is dormant in resting cells but becomes activated upon cell stimulation to
      produce superoxide, a precursor of microbicidal oxidants. Nox2 activation
      requires two switches to be turned on simultaneously: a conformational change of
      the cytosolic protein p47(phox) and GDP/GTP exchange on the small GTPase Rac.
      These proteins, in an active form, bind to their respective targets, p22(phox)
      and p67(phox), leading to productive oxidase assembly at the membrane. Although
      arachidonic acid (AA) efficiently activates Nox2 both in vivo and in vitro, the
      mechanism has not been fully understood, except that AA induces p47(phox)
      conformational change. Here we show that AA elicits GDP-to-GTP exchange on Rac at
      the cellular level, consistent with its role as a potent Nox2 activator. However,
      even when constitutively active forms of p47(phox) and Rac1 are both expressed in
      HeLa cells, superoxide production by Nox2 is scarcely induced in the absence of
      AA. These active proteins also fail to effectively activate Nox2 in a cell-free
      reconstituted system without AA. Without affecting Rac-GTP binding to p67(phox),
      AA induces the direct interaction of Rac-GTP-bound p67(phox) with the C-terminal
      cytosolic region of Nox2. p67(phox)-Rac-Nox2 assembly and superoxide production
      are both abrogated by alanine substitution for Tyr-198, Leu-199, and Val-204 in
      the p67(phox) activation domain that localizes the C-terminal to the Rac-binding
      domain. Thus the "third" switch (AA-inducible interaction of p67(phox).Rac-GTP
      with Nox2) is required to be turned on at the same time for Nox2 activation. 

PMID- 25056960
TI  - Discrepancies in identification of left atrial enlargement using left atrial
      volume versus left atrial-to-aortic root ratio in dogs.
AB  - BACKGROUND: Left atrial size is prognostically important in dogs with myxomatous
      mitral valve disease (MMVD). HYPOTHESIS/OBJECTIVES: To compare the level of
      agreement in identification of left atrial enlargement (LAE) between the left
      atrial-to-aortic root ratio (LA : Ao) and left atrial volume using the biplane
      area-length method indexed to body weight (LA Vol/BW). ANIMALS: Sixty dogs with
      MMVD and 22 normal dogs were prospectively studied with 2-dimensional
      echocardiography. METHODS: The upper limit of normal for LA Vol/BW was defined as
      1.1 mL/kg. LA : Ao was deemed normal if <=1.5. To define overall disease
      severity, each dog was assigned a mitral regurgitation severity score (MRSS)
      based on echocardiographic parameters that did not include left atrial size.
      ACVIM staging also was utilized. RESULTS: Of 60 affected dogs, 20 were ACVIM
      Stage B1, 25 were Stage B2, and 15 were Stage C. LA Vol/BW identified LAE in 12
      cases in which LA : Ao was normal; 7 of these were Stage B1 and 5 were Stage B2.
      This diagnostic disagreement was significant (P = .00012). Of the 12 cases in
      which diagnostic discrepancies were identified, 5/5 of the B2 dogs and 3/7 B1
      dogs had a moderate MRSS, whereas 4/7 B1 dogs had a mild MRSS. No diagnostic
      discrepancies between LA : Ao and LA Vol/BW were apparent in dogs with a severe
      MRSS. CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows evidence of
      diagnostic disagreement between LA : Ao and LA Vol/BW for assessment of LAE. LA
      Vol/BW may be superior to LA : Ao for identification of mild LAE.

PMID- 25056961
TI  - Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal
      damage by neutrophils against Exserohilum rostratum.
AB  - Exserohilum rostratum caused a multistate fungal meningitis outbreak following
      iatrogenic inoculation of contaminated methylprednisolone in the United States.
      To gain insight into the immunopathogenesis of this infection, we studied the
      innate host responses of human neutrophils against E. rostratum conidia and
      hyphae with or without methylprednisolone. The neutrophil-induced percentage
      fungal damage against conidia and hyphae was effector-to-target ratio dependent
      (<=55%). While methylprednisolone did not affect neutrophil-induced fungal damage
      by treatment of Exserohilum or neutrophils, it compromised phagocytosis of
      conidia (P < 0.05). These findings suggest that methylprednisolone-treated
      neutrophils may have altered phagocytic clearance of Exserohilum conidia,
      reducing host capacity to contain the invasive process. 

PMID- 25056962
TI  - Inhaled corticosteroids and Aspergillus fumigatus isolation in cystic fibrosis.
AB  - Aspergillus fumigatus isolation in cultures from respiratory specimens of
      patients with cystic fibrosis (CF) is quite common; however, the role of A.
      fumigatus as a pathogen and whether its presence is associated with progression
      of pulmonary disease remain unclear. We investigated the association between
      inhaled corticosteroids and the recovery of A. fumigatus by performing a
      retrospective cohort study of CF patients born between 1988 and 1996. The
      patients' medical records from their first visit to the CF Center until December
      2010 were reviewed. Outcomes were the occurrence of A. fumigatus first isolation,
      chronic colonization, or the last visit at the CF Center. A number of possible
      confounders were included in the multivariate logistic regression analysis in
      order to identify an independent association between inhaled corticosteroids and
      colonization status. A total of 121 patients were included in the study. Thirty
      nine patients (32.2%) had at least one positive culture and 14 (11.6%) developed
      chronic colonization. Multivariate logistic regression analysis was used to
      determine the independent effect of inhaled corticosteroids on the odds of first
      isolation (odds ratio [OR], 1.165; 95% confidence interval [CI], 1.015-1.337; P =
      0.029) and chronic colonization (OR, 1.180; 95% CI, 1.029-1.353; P = 0.018). In
      conclusion, A. fumigatus first isolation and chronic colonization are associated
      with the duration of inhaled corticosteroid treatment. 

PMID- 25056963
TI  - Double metal ions competitively control the guest-sensing process: a facile
      approach to stimuli-responsive supramolecular gels.
AB  - A facile approach to the design of stimuli-responsive supramolecular gels (SRSGs)
      termed double-metal-ion competitive coordination control is reported. By this
      means, the fluorescence signals and guest-selective responsiveness of the SRSGs
      are controlled by the competitive coordination of two different metal ions with
      the gelators and the target guest. To demonstrate this approach, a gelator G2
      based on multiple self-assembly driving forces was synthesized. G2 could form
      Ca(2+) -coordinated metallogel CaG with strong aggregation-induced emission
      (AIE). Doping of CaG with Cu(2+) results in AIE quenching of CaG and formation of
      Ca(2+) - and Cu(2+) -based metallogel CaCuG. CaCuG could fluorescently detect CN(
      ) with specific selectivity through the competitive coordination of CN(-) with
      the Cu(2+) and the coordination of Ca(2+) with G2 again. This approach may open
      up routes to novel stimuli-responsive supramolecular materials. 

PMID- 25056964
TI  - Tranexamic acid suppresses ultraviolet B eye irradiation-induced melanocyte
      activation by decreasing the levels of prohormone convertase 2 and alpha
      melanocyte-stimulating hormone.
AB  - BACKGROUND: Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a
      medicinal amino acid used in skin whitening care. This study examined the effects
      of tranexamic acid on the melanocyte activation of the skin induced by an
      ultraviolet (UV) B eye irradiation. METHODS: The eye or ear was locally exposed
      to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining
      body surface with aluminum foil. RESULTS: UVB eye irradiation induced melanocyte
      activation of the skin, similar to that observed following UVB ear irradiation,
      which was suppressed by the administration of tranexamic acid treatment. The
      plasma alpha-melanocyte-stimulating hormone (alpha-MSH) content was increased by
      UVB irradiation of the eye; however, the increase in alpha-MSH was suppressed by
      tranexamic acid treatment. In addition, UVB eye irradiation induced the up
      regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the
      increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid
      treatment. CONCLUSIONS: These results clearly indicate that tranexamic acid
      decreases the expression of PC2, which cleavages from proopiomelanocortin to
      alpha-MSH in the pituitary gland, thereby suppressing melanocyte activation.

PMID- 25056965
TI  - Single-particle tracking reveals that free ribosomal subunits are not excluded
      from the Escherichia coli nucleoid.
AB  - Biochemical and genetic data show that ribosomes closely follow RNA polymerases
      that are transcribing protein-coding genes in bacteria. At the same time,
      electron and fluorescence microscopy have revealed that ribosomes are excluded
      from the Escherichia coli nucleoid, which seems to be inconsistent with fast
      translation initiation on nascent mRNA transcripts. The apparent paradox can be
      reconciled if translation of nascent mRNAs can start throughout the nucleoid
      before they relocate to the periphery. However, this mechanism requires that free
      ribosomal subunits are not excluded from the nucleoid. Here, we use single
      particle tracking in living E. coli cells to determine the fractions of free
      ribosomal subunits, classify individual subunits as free or mRNA-bound, and
      quantify the degree of exclusion of bound and free subunits separately. We show
      that free subunits are not excluded from the nucleoid. This finding strongly
      suggests that translation of nascent mRNAs can start throughout the nucleoid,
      which reconciles the spatial separation of DNA and ribosomes with
      cotranscriptional translation. We also show that, after translation inhibition,
      free subunit precursors are partially excluded from the compacted nucleoid. This
      finding indicates that it is active translation that normally allows ribosomal
      subunits to assemble on nascent mRNAs throughout the nucleoid and that the
      effects of translation inhibitors are enhanced by the limited access of ribosomal
      subunits to nascent mRNAs in the compacted nucleoid. 

PMID- 25056966
TI  - Sequence specificity of human telomerase.

PMID- 25056967
TI  - Transcriptional regulation of the sodium-coupled neutral amino acid transporter
      (SNAT2) by 17beta-estradiol.
AB  - The sodium-coupled neutral amino acid transporter 2 (SNAT2) translocates small
      neutral amino acids into the mammary gland to promote cell proliferation during
      gestation. It is known that SNAT2 expression increases during pregnancy, and in
      vitro studies indicate that this transporter is induced by 17beta-estradiol. In
      this study, we elucidated the mechanism by which 17beta-estradiol regulates the
      transcription of SNAT2. In silico analysis revealed the presence of a potential
      estrogen response element (ERE) in the SNAT2 promoter. Reporter assays showed an
      increase in SNAT2 promoter activity when cotransfected with estrogen receptor
      alpha (ER-alpha) after 17beta-estradiol stimulation. Deletion of the ERE reduced
      estradiol-induced promoter activity by 63%. Additionally, EMSAs and supershift
      assays showed that ER-alpha binds to the SNAT2 ERE and that this binding competes
      with the interaction of ER-alpha with its consensus ERE. An in vivo ChIP assay
      demonstrated that the binding of ER-alpha to the SNAT2 promoter gradually
      increased in the mammary gland during gestation and that maximal binding occurred
      at the highest 17beta-estradiol serum concentration. Liquid chromatography
      elevated energy mass spectrometry and Western blot analysis revealed that the
      SNAT2 ER-alpha-ERE complex contained poly(ADP-ribose) polymerase 1, Lupus Ku
      autoantigen protein p70, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
      proteins and that the silencing of each of these proteins nearly abolished 17beta
      estradiol-stimulated SNAT2 promoter activity. Nuclear levels of GAPDH increased
      progressively during gestation in the mammary gland, and GAPDH binding was
      nucleotide-specific for the SNAT2 ERE. Thus, this study provides new insights
      into how the mammary epithelium adapts to control amino acid uptake through the
      transcriptional regulation of the SNAT2 transporter via 17beta-estradiol. 

PMID- 25056968
TI  - Surface expression of the hRSV nucleoprotein impairs immunological synapse
      formation with T cells.
AB  - Human respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis
      and pneumonia in young children worldwide. The recurrent hRSV outbreaks and
      reinfections are the cause of a significant public health burden and associate
      with an inefficient antiviral immunity, even after disease resolution. Although
      several mouse- and human cell-based studies have shown that hRSV infection
      prevents naive T-cell activation by antigen-presenting cells, the mechanism
      underlying such inhibition remains unknown. Here, we show that the hRSV
      nucleoprotein (N) could be at least partially responsible for inhibiting T-cell
      activation during infection by this virus. Early after infection, the N protein
      was expressed on the surface of epithelial and dendritic cells, after interacting
      with trans-Golgi and lysosomal compartments. Further, experiments on supported
      lipid bilayers loaded with peptide-MHC (pMHC) complexes showed that surface
      anchored N protein prevented immunological synapse assembly by naive CD4(+) T
      cells and, to a lesser extent, by antigen-experienced T-cell blasts. Synapse
      assembly inhibition was in part due to reduced T-cell receptor (TCR) signaling
      and pMHC clustering at the T-cell-bilayer interface, suggesting that N protein
      interferes with pMHC-TCR interactions. Moreover, N protein colocalized with the
      TCR independently of pMHC, consistent with a possible interaction with TCR
      complex components. Based on these data, we conclude that hRSV N protein
      expression at the surface of infected cells inhibits T-cell activation. Our study
      defines this protein as a major virulence factor that contributes to impairing
      acquired immunity and enhances susceptibility to reinfection by hRSV.

PMID- 25056969
TI  - Association of napping and night-time sleep with impaired glucose regulation,
      insulin resistance and glycated haemoglobin in Chinese middle-aged adults with no
      diabetes: a cross-sectional study.
AB  - OBJECTIVE: To assess associations between napping and night-time sleep duration
      with impaired glucose regulation, insulin resistance (IR) and glycated
      haemoglobin (HbA1c). DESIGN: Cross-sectional study. SETTING: Fujian Province,
      China, from June 2011 to January 2012. PARTICIPANTS: This study enrolled 9028
      participants aged 40-65 years. Data of 7568 participants with no diabetes were
      included for analysis. Type 2 diabetes was defined applying WHO criteria. OUTCOME
      MEASURES: Participants' daytime napping and night-time sleep duration data were
      collected using a standardised self-reported Chinese-language questionnaire about
      sleep frequency and quality. Anthropometric and laboratory parameters were also
      measured. IR was defined as a HOMA-IR index value >2.50. ORs and 95% CIs were
      derived from multivariate logistic regression models. RESULTS: Participants (mean
      age 51.1+/-7.0 years) included 3060 males and 4508 females with average night
      time sleep of 7.9 h. A higher proportion of males napped than females. After
      adjustment for potential confounders, ORs for HbA1c >6.0% were 1.28 and 1.26 for
      those napping <=1 h and >1 h (p=0.002 and p=0.018), respectively. Statistically
      significant differences in IR between nappers and non-nappers were only marginal
      clinically. Odds for HbA1c >6.0% were significantly lower in participants with
      longer night-time sleep durations than in the reference group (>8 h vs 6-8 h).
      Odds for IR were significantly lower in participants whose night-time sleep hours
      deviated from the reference group (<6 h, >8 h vs 6-8 h) CONCLUSIONS: Chinese
      middle-aged adults with no diabetes who napped had higher HbA1c and IR; those
      with shorter night-time sleep durations had increased HbA1c. Night-time sleep
      hours that are either <6 or >8 tend to be associated with lower odds for IR.
      Further studies are necessary to determine the underlying clinical significance
      and mechanisms behind these associations.

PMID- 25056970
TI  - Annexin A11 (ANXA11) gene polymorphisms are associated with sarcoidosis in a Han
      Chinese population: a case-control study.
AB  - OBJECTIVES: To further identify the single-nucleotide polymorphisms (SNPs) that
      contribute to the genetic susceptibility to sarcoidosis, we examined the
      potential association between sarcoidosis and 15 SNPs of the ANXA11 gene. DESIGN:
      A case-control study. SETTING: A tuberculosis unit in a hospital of the
      university in China. PARTICIPANTS: Participants included 412 patients with
      sarcoidosis and 418 healthy controls. METHODS: The selected SNPs were genotyped
      using the MALDI-TOF in the MassARRAY system. RESULTS: Statistically significant
      differences were found in the allelic or genotypic frequencies of the rs2789679,
      rs1049550 and rs2819941 in the ANXA11 gene between patients with sarcoidosis and
      controls. The rs2789679 A allele (p=0.00004, OR=1.42, 95% CI 1.17 to 1.73) and
      rs2819941 T allele (p=0.0006, OR=1.41, 95% CI 1.16 to 1.71) were significantly
      more frequent in patients with sarcoidosis compared with controls. The frequency
      of the rs1049550 T allele (p=0.000002, OR=0.61, 95% CI 0.49 to 0.74) in patients
      with sarcoidosis was significantly lower than that in controls. The multi-SNP
      model reveals that rs1049550 is the only independent SNP association effect after
      accounting for the other two marginally associated SNPs. In block 2 (rs1049550
      rs2573351), the T-C haplotype occurred significantly less frequently (p=0.001),
      whereas the C-C haplotypes occurred more frequently (p=0.0001) in patients with
      sarcoidosis than controls. Furthermore, genotype frequency distribution revealed
      that, in rs1049550, the CC genotype was significantly more in patients with chest
      X-ray (CXR) stage I sarcoidosis than in patients with CXR stage II-IV sarcoidosis
      (p=0.012). CONCLUSIONS: These findings point to a role for the polymorphisms of
      ANXA11 in sarcoidosis in a Chinese Han population, and may be informative for
      future genetic studies on sarcoidosis.

PMID- 25056971
TI  - The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and
      results of the research prioritisation survey process.
AB  - OBJECTIVES: The Sight Loss and Vision Priority Setting Partnership aimed to
      identify research priorities relating to sight loss and vision through
      consultation with patients, carers and clinicians. These priorities can be used
      to inform funding bodies' decisions and enhance the case for additional research
      funding. DESIGN: Prospective survey with support from the James Lind Alliance.
      SETTING: UK-wide National Health Service (NHS) and non-NHS. PARTICIPANTS:
      Patients, carers and eye health professionals. Academic researchers were excluded
      solely from the prioritisation process. The survey was disseminated by patient
      groups, professional bodies, at conferences and through the media, and was
      available for completion online, by phone, by post and by alternative formats
      (Braille and audio). OUTCOME MEASURE: People were asked to submit the questions
      about prevention, diagnosis and treatment of sight loss and eye conditions that
      they most wanted to see answered by research. Returned survey questions were
      reviewed by a data assessment group. Priorities were established across eye
      disease categories at final workshops. RESULTS: 2220 people responded generating
      4461 submissions. Sixty-five per cent of respondents had sight loss and/or an eye
      condition. Following initial data analysis, 686 submissions remained which were
      circulated for interim prioritisation (excluding cataract and ocular cancer
      questions) to 446 patients/carers and 218 professionals. The remaining 346
      questions were discussed at final prioritisation workshops to reach agreement of
      top questions per category. CONCLUSIONS: The exercise engaged a diverse community
      of stakeholders generating a wide range of conditions and research questions. Top
      priority questions were established across 12 eye disease categories.

PMID- 25056972
TI  - Patient and public involvement in the early stages of clinical trial development:
      a systematic cohort investigation.
AB  - BACKGROUND: Randomised controlled trials (RCTs) are considered particularly
      likely to benefit from patient and public involvement (PPI). Decisions made by
      professional researchers at the outset may go on to have a significant impact on
      the potential for PPI contributions. OBJECTIVE: To increase knowledge of PPI
      within the early development of RCTs by systematically describing the reported
      level, nature and acceptability of proposed PPI to the funders. METHODS:
      Documentation from the outline application process for all RCTs that received
      funding from the Health Technology Assessment (HTA) Programme 2006-2010 was
      requested. For each application, data were extracted on trial characteristics,
      references to PPI in the development of the outline application and funding Board
      feedback, and plans for PPI in the full application and after the trial was
      funded. RESULTS: 110 applications were eligible with outline applications
      available for 90 (82%). The cohort covered a wide range of interventions and
      conditions. 54% (49/90) provided some information about PPI. 26 (28.9%) indicated
      PPI within the development of the outline application itself; 32 (35.6%) planned
      involvement in the full application and 43 (48%) once the trial was funded.
      Recruitment at diagnosis and surgical interventions were less likely to describe
      PPI. Blinded trials and trials in which participants may receive placebo only,
      more frequently described PPI activity. The HTA commissioning Board feedback
      rarely referred to PPI. CONCLUSIONS: Incorporation of PPI within the development
      of the outline application or specification of plans for future involvement was
      low. Funder requests for applicants to provide information on PPI and
      justification for its absence should be welcomed but further research is needed
      to identify the impact of this on its contributions to research. Comments on PPI
      by reviewers should be directional rather than state that an increase is
      required. Challenges facing applicants in initiating PPI prior to funding need to
      be addressed.

PMID- 25056973
TI  - Brazilian medicinal plants to treat upper respiratory tract and bronchial
      illness: systematic review and meta-analyses-study protocol.
AB  - INTRODUCTION: Respiratory illness, often associated with cough and sputum, is
      frequent. In Brazil, herbal medicines are often recommended as a first-line
      treatment for respiratory illness. There exists uncertainty regarding the
      effectiveness of these treatments. No systematic review has evaluated Brazilian
      medicinal plants (BMP) to treat upper respiratory tract and bronchial illness
      (URTI). METHODS AND ANALYSIS: We will conduct a systematic review and, if
      appropriate, a series of meta-analyses evaluating the safety and effectiveness of
      BMP for URTI. Eligible randomised controlled trials and observational studies
      will enrol adult or paediatric patients presenting with URTI treated by BMP
      approved by the Brazilian Health Surveillance Agency compared with placebo, no
      treatment or an alternative therapy. Our search will include the Cochrane Central
      Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute
      Respiratory Illness Group's Specialized Register; MEDLINE; EMBASE; CINAHL
      (Cumulative Index to Nursing and Allied Health Literature); Web of Science; AMED;
      LILACS; CAB abstracts; clinical trial.gov; the WHO Trial Register and the
      Brazilian thesis database (CAPES) without any language restrictions. Outcomes of
      interest are time to resolution of clinical symptoms and/or signs (cough, sputum
      production or activity limitations), severity of symptoms prior to resolution and
      major/minor adverse events. Teams of reviewers will, independently and in
      duplicate, screen titles and abstracts and the complete full text to determine
      eligibility. For eligible studies, reviewers will perform data abstraction and
      assess risk of bias of eligible trials. When appropriate, we will conduct meta
      analyses. We will also assess the quality of body of evidence (confidence in
      estimates of effect) for each of the outcomes using the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS
      AND DISSEMINATION: The systematic review will be published in a peer-reviewed
      journal. Brief reports of review findings will be disseminated directly to
      appropriate audiences via email and other modes of communication. The review will
      guide healthcare practice and policy in Brazil. TRIAL REGISTRATION NUMBER:
      Prospero CRD42014007057.

PMID- 25056974
TI  - Drug treatment of macular oedema secondary to central retinal vein occlusion: a
      network meta-analysis.
AB  - OBJECTIVE: To indirectly compare aflibercept, bevacizumab, dexamethasone,
      ranibizumab and triamcinolone for treatment of macular oedema secondary to
      central retinal vein occlusion using a network meta-analysis (NMA). DESIGN NMA
      DATA SOURCES: The following databases were searched from January 2005 to March
      2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL;
      Science Citation Index and Conference Proceedings Citation Index-Science.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Only randomised controlled trials
      assessing patients with macular oedema secondary to central retinal vein
      occlusion were included. Studies had to report either proportions of patients
      gaining >=3 lines, losing >=3 lines, or the mean change in best corrected visual
      acuity. Two authors screened titles and abstracts, extracted data and undertook
      risk of bias assessment. Bayesian NMA was used to compare the different
      interventions. RESULTS: Seven studies, assessing five drugs, were judged to be
      sufficiently comparable for inclusion in the NMA. For the proportions of patients
      gaining >=3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg
      and aflibercept 2 mg had a higher probability of being more effective than sham
      and dexamethasone. A smaller proportion of patients treated with triamcinolone 4
      mg, ranibizumab 0.5 mg or aflibercept 2 mg lost >=3 lines of vision compared to
      those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab
      0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of
      improvement in the mean best corrected visual acuity compared to those treated
      with sham injections. CONCLUSIONS: We found no evidence of differences between
      ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The
      antivascular endothelial growth factors (VEGFs) are likely to be favoured because
      they are not associated with steroid-induced cataract formation. Aflibercept may
      be preferred by clinicians because it might require fewer injections. SYSTEMATIC
      REVIEW REGISTRATION: Not registered.

PMID- 25056975
TI  - Perceptions of chronically ill and healthy consumers about electronic personal
      health records: a comparative empirical investigation.
AB  - OBJECTIVE: To develop a model of consumer perceptions of electronic personal
      health records (PHRs) and validate it in a comparative study between consumers
      who report having a chronic illness and those who report being well. MATERIALS
      AND METHODS: A model of PHR use motivators and barriers was built and tested
      through a national survey across Canada. Data were collected from 800
      individuals, 18 years or older. Half reported having a chronic illness or
      disability and half reported being well. Analyses were performed with structural
      equation modelling techniques. RESULTS: A total of 389 answers from chronically
      ill and 383 from well participants were collected. Perceived usefulness was the
      key explanation of the intention to use PHRs for both ill and well people (total
      effect of 0.601 and 0.565, respectively) followed by security, privacy and trust
      in PHRs (total effect of 0.377 and 0.479, respectively). Conversely, computer
      anxiety was perceived as a significant barrier (total effect of -0.327 for ill
      individuals and -0.212 for well individuals). DISCUSSION: The model proposed was
      appropriate in explaining key consumer positive and negative perceptions on
      electronic PHR use. We found little difference in perceptions of electronic PHRs
      between chronically ill and well individuals, although self-reporting their
      health status might have influenced the results. CONCLUSIONS: To increase the
      adoption rate of electronic PHRs among both chronically ill and well consumers it
      is necessary to reinforce consumer perceptions of the usefulness of and trust in
      these eHealth technologies while mitigating their anxieties about computer use in
      general.

PMID- 25056976
TI  - Undiagnosed diabetes from cross-sectional GP practice data: an approach to
      identify communities with high likelihood of undiagnosed diabetes.
AB  - OBJECTIVES: To estimate undiagnosed diabetes prevalence from general practitioner
      (GP) practice data and identify areas with high levels of undiagnosed and
      diagnosed diabetes. DESIGN: Data from the North-West Adelaide Health Survey
      (NWAHS) were used to develop a model which predicts total diabetes at a small
      area. This model was then applied to cross-sectional data from general practices
      to predict the total level of expected diabetes. The difference between total
      expected and already diagnosed diabetes was defined as undiagnosed diabetes
      prevalence and was estimated for each small area. The patterns of diagnosed and
      undiagnosed diabetes were mapped to highlight the areas of high prevalence.
      SETTING: North-West Adelaide, Australia. PARTICIPANTS: This study used two
      population samples-one from the de-identified GP practice data (n=9327 active
      patients, aged 18 years and over) and another from NWAHS (n=4056, aged 18 years
      and over). MAIN OUTCOME MEASURES: Total diabetes prevalence, diagnosed and
      undiagnosed diabetes prevalence at GP practice and Statistical Area Level 1.
      RESULTS: Overall, it was estimated that there was one case of undiagnosed
      diabetes for every 3-4 diagnosed cases among the 9327 active patients analysed.
      The highest prevalence of diagnosed diabetes was seen in areas of lower
      socioeconomic status. However, the prevalence of undiagnosed diabetes was
      substantially higher in the least disadvantaged areas. CONCLUSIONS: The method
      can be used to estimate population prevalence of diabetes from general practices
      wherever these data are available. This approach both flags the possibility that
      undiagnosed diabetes may be a problem of less disadvantaged social groups, and
      provides a tool to identify areas with high levels of unmet need for diabetes
      care which would enable policy makers to apply geographic targeting of effective
      interventions.

PMID- 25056977
TI  - Mapping patient pathways and estimating resource use for point of care versus
      standard testing and treatment of chlamydia and gonorrhoea in genitourinary
      medicine clinics in the UK.
AB  - OBJECTIVES: We aimed to explore patient pathways using a chlamydia/gonorrhoea
      point-of-care (POC) nucleic acid amplification test (NAAT), and estimate and
      compare the costs of the proposed POC pathways with the current pathways using
      standard laboratory-based NAAT testing. DESIGN/PARTICIPANTS: Workshops were
      conducted with healthcare professionals at four sexual health clinics
      representing diverse models of care in the UK. They mapped out current pathways
      that used chlamydia/gonorrhoea tests, and constructed new pathways using a POC
      NAAT. Healthcare professionals' time was assessed in each pathway. OUTCOME
      MEASURE: The proposed POC pathways were then priced using a model built in
      Microsoft Excel, and compared to previously published costs for pathways using
      standard NAAT-based testing in an off-site laboratory. RESULTS: Pathways using a
      POC NAAT for asymptomatic and symptomatic patients and chlamydia/gonorrhoea-only
      tests were shorter and less expensive than most of the current pathways. Notably,
      we estimate that POC testing as part of a sexual health screen for symptomatic
      patients, or as stand-alone chlamydia/gonorrhoea testing, could reduce costs per
      patient by as much as L16 or L6, respectively. In both cases, healthcare
      professionals' time would be reduced by approximately 10 min per patient.
      CONCLUSIONS: POC testing for chlamydia/gonorrhoea in a clinical setting may
      reduce costs and clinician time, and may lead to more appropriate and quicker
      care for patients. Further study is warranted on how to best implement POC
      testing in clinics, and on the broader clinical and cost implications of this
      technology.

PMID- 25056978
TI  - Clinical significance of low forced expiratory flow between 25% and 75% of vital
      capacity following treated pulmonary tuberculosis: a cross-sectional study.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence and determinants
      of post-tuberculosis chronic respiratory signs, as well as the clinical impact of
      a low forced expiratory flow between 25% and 75% (FEF25-75%) in a group of
      individuals previously treated successfully for pulmonary tuberculosis. DESIGN:
      This was a cross-sectional study involving individuals in their post-tuberculosis
      treatment period. They all underwent a spirometry following the 2005 criteria of
      the American Thoracic Society/European Respiratory Society. Distal airflow
      obstruction (DAO) was defined by an FEF25-75% <65% and a ratio forced expiratory
      volume during the first second (FEV1)/forced vital capacity (FVC) >= 0.70.
      Logistic regression models were used to investigate the determinants of
      persisting respiratory symptoms following antituberculous treatment. SETTING:
      This study was carried out in the tuberculosis diagnosis and treatment centre at
      Yaounde Jamot Hospital, which serves as a referral centre for tuberculosis and
      respiratory diseases for the capital city of Cameroon (Yaounde) and surrounding
      areas. PARTICIPANTS: All consecutive patients in their post-tuberculosis
      treatment period were consecutively enrolled between November 2012 and April
      2013. RESULTS: Of the 177 patients included, 101 (57.1%) were men, whose median
      age (25th-75th centiles) was 32 (24-45.5) years. At least one chronic respiratory
      sign was present in 110 (62.1%) participants and DAO was found in 67 (62.9%).
      Independent determinants of persisting respiratory signs were the duration of
      symptoms prior to tuberculosis diagnosis higher than 12 weeks (adjusted OR 2.91;
      95% CI 1.12 to 7.60, p=0.029) and presence of DAO (2.22; 1.13 to 4.38, p=0.021).
      CONCLUSIONS: FEF25-75%<65% is useful for the assessment and diagnosis of post
      tuberculous DAO. Mass education targeting early diagnosis of pulmonary
      tuberculosis can potentially reduce the prevalence of post-tuberculosis
      respiratory signs and distal airflow obstruction.

PMID- 25056979
TI  - The first 1000 days of life: prenatal and postnatal risk factors for morbidity
      and growth in a birth cohort in southern India.
AB  - OBJECTIVE: To estimate the burden and assess prenatal and postnatal determinants
      of illnesses experienced by children residing in a semiurban slum, during the
      first 1000 days of life. DESIGN: Community-based birth cohort SETTING: Southern
      India PARTICIPANTS: Four hundred and ninety-seven children of 561 pregnant women
      recruited and followed for 2 years with surveillance and anthropometry. MAIN
      OUTCOME MEASURE: Incidence rates of illness; rates of clinic visits and
      hospitalisations; factors associated with low birth weight, various illnesses and
      growth. RESULTS: Data on 10 377.7 child-months of follow-up estimated an average
      rate of 14.8 illnesses/child-year. Gastrointestinal and respiratory illnesses
      were 20.6% and 47.8% of the total disease burden, respectively. The
      hospitalisation rate reduced from 46/100 child-years during infancy to 19/100
      child-years in the second year. Anaemia during pregnancy (OR=2.3, 95% CI=1.08 to
      5.18), less than four antenatal visits (OR=6.8, 95% CI=2.1 to 22.5) and preterm
      birth (OR=3.3, 95% CI=1.1 to 9.7) were independent prenatal risk factors for low
      birth weight. Female gender (HR=0.88, 95% CI=0.79 to 0.99) and 6 months of
      exclusive breast feeding (HR=0.76, 95% CI=0.66 to 0.88) offered protection
      against all morbidity. Average monthly height and weight gain were lower in
      female child and children exclusively breast fed for 6 months. CONCLUSIONS: The
      high morbidity in Indian slum children in the first 1000 days of life was mainly
      due to prenatal factors and gastrointestinal and respiratory illness.
      Policymakers need disease prevalence and pathways to target high-risk groups with
      appropriate interventions in the community.

PMID- 25056980
TI  - Validation of chronic obstructive pulmonary disease recording in the Clinical
      Practice Research Datalink (CPRD-GOLD).
AB  - OBJECTIVES: The optimal method of identifying people with chronic obstructive
      pulmonary disease (COPD) from electronic primary care records is not known. We
      assessed the accuracy of different approaches using the Clinical Practice
      Research Datalink, a UK electronic health record database. SETTING: 951
      participants registered with a CPRD practice in the UK between 1 January 2004 and
      31 December 2012. Individuals were selected for >=1 of 8 algorithms to identify
      people with COPD. General practitioners were sent a brief questionnaire and
      additional evidence to support a COPD diagnosis was requested. All information
      received was reviewed independently by two respiratory physicians whose opinion
      was taken as the gold standard. PRIMARY OUTCOME MEASURE: The primary measure of
      accuracy was the positive predictive value (PPV), the proportion of people
      identified by each algorithm for whom COPD was confirmed. RESULTS: 951
      questionnaires were sent and 738 (78%) returned. After quality control, 696
      (73.2%) patients were included in the final analysis. All four algorithms
      including a specific COPD diagnostic code performed well. Using a diagnostic code
      alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry
      plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but
      reduced case numbers by 10%. Algorithms without specific diagnostic codes had low
      PPVs (range 12.2-44.4%). CONCLUSIONS: Patients with COPD can be accurately
      identified from UK primary care records using specific diagnostic codes.
      Requiring spirometry or COPD medications only marginally improved accuracy. The
      high accuracy applies since the introduction of an incentivised disease register
      for COPD as part of Quality and Outcomes Framework in 2004.

PMID- 25056981
TI  - RAndomised controlled trial to imProve depressIon and the quality of life of
      people with Dementia using cognitive bias modification: RAPID study protocol.
AB  - INTRODUCTION: Depressive symptoms are common and undermine the quality of life of
      people with Alzheimer's disease (AD). Cholinesterase inhibitors and
      antidepressants have all but no effect on the mood of patients, and their use
      increases adverse events. Cognitive bias modification (CBM) targets attentional
      and interpretative biases associated with anxiety, dysphoria and depression and
      may be useful to treat depression in AD (DAD). This trial aims to determine the
      effect of CBM on depression scores and the quality of life of people with DAD.
      METHODS AND ANALYSIS: Randomised, double-blind, parallel, controlled trial of CBM
      (1:1 allocation ratio). Participants will be 80 adults with probable AD living in
      the Western Australian community who score 8 or more on the Cornell Scale for
      Depression in Dementia (CSDD). They will have mild to moderate dementia (Mini
      Mental State Examination-MMSE score >=15) and will be free of severe sensory
      impairment or suicidal intent. The intervention will consist of 10 40 min
      sessions of CBM delivered over 2 weeks using a high-resolution monitor using a
      local computer station at the Western Australian Centre for Health and Ageing.
      The primary outcomes of interest are the 2-week change, from baseline, in the
      severity of CSDD scores and the Quality of Life AD (QoL-AD) scores. Secondary
      outcomes include changes in the CSDD, QoL-AD after 12 weeks, and changes in MMSE
      scores, negative attentional and interpretative bias and the proportion of
      participants with CSDD <8 after 2 and 12 weeks. ETHICS AND DISSEMINATION: The
      study will comply with the principles of the Declaration of Helsinki and
      participants will provide written informed consent. The Ethics Committee of the
      Royal Perth Hospital will approve and oversee the study (REG14-036). The results
      of this trial will provide level 2 evidence of efficacy for CBM as a treatment of
      DAD. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials
      Registry number ACTRN12614000420640, date registered 06/04/2014.

PMID- 25056982
TI  - 'I'm not a druggie, I'm just a diabetic': a qualitative study of stigma from the
      perspective of adults with type 1 diabetes.
AB  - OBJECTIVES: While health-related stigma has been the subject of considerable
      research in other conditions (eg, HIV/AIDS, obesity), it has not received
      substantial attention in diabetes. Our aim was to explore perceptions and
      experiences of diabetes-related stigma from the perspective of adults with type 1
      diabetes mellitus (T1DM). DESIGN: A qualitative study using semistructured
      interviews, which were audio recorded, transcribed and subject to thematic
      analysis. SETTING: All interviews were conducted in non-clinical settings in
      metropolitan areas of Victoria, Australia. PARTICIPANTS: Adults aged >=18 years
      with T1DM living in Victoria were eligible to take part. Participants were
      recruited primarily through the state consumer organisation representing people
      with diabetes. A total of 27 adults with T1DM took part: 15 (56%) were women;
      median IQR age was 42 (23) years and diabetes duration was 15 (20) years).
      RESULTS: Australian adults with T1DM perceive and experience T1DM-specific stigma
      as well as stigma-by-association with type 2 diabetes. Such stigma is
      characterised by blame, negative social judgement, stereotyping, exclusion,
      rejection and discrimination. Participants identified the media, family and
      friends, healthcare professionals and school teachers as sources of stigma. The
      negative consequences of this stigma span numerous life domains, including impact
      on relationships and social identity, emotional well-being and behavioural
      management of T1DM. This stigma also led to reluctance to disclose the condition
      in various environments. Adults with T1DM can be both the target and the source
      of diabetes-related stigma. CONCLUSIONS: Stigmatisation is part of the social
      experience of living with T1DM for Australian adults. Strategies and
      interventions to address and mitigate this diabetes-related stigma need to be
      developed and evaluated.

PMID- 25056984
TI  - Role of (18) F-FDOPA PET/CT imaging in endocrinology.
AB  - (18) F-FDOPA (6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine)-based PET/CT
      imaging can be a useful tool for the detection of different neuroendocrine
      tumours (NETs). (18) F-FDOPA is taken up into the cells via the neutral amino
      acid transporter (LAT1/4F2hc). This transporter is also coupled to the mammalian
      target of rapamycin (mTOR) signalling pathway. (18) F-FDOPA PET/CT may be
      performed for confirmation of diagnosis of pheochromocytoma/paraganglioma,
      staging at initial presentation, restaging and follow-up of patients. In SDHx
      related syndromes, (18) F-FDG PET/CT should be performed in addition to (18) F
      FDOPA PET/CT. (18) F-FDOPA PET/CT is also invaluable in the detection
      staging/restaging of carcinoid tumours and has greater sensitivity as compared to
      somatostatin receptor scintigraphy. (18) F-FDOPA PET/CT can also distinguish
      between focal vs diffuse CHI. It is not as useful in adult hyperinsulinism due to
      increased background uptake, but the problem may be overcome with the help of
      premedication with carbidopa. It has limited use in pancreatic NETs. (18) F-FDOPA
      PET/CT is a good modality for detection of persistent and residual medullary
      thyroid cancer (MTC), but (18) F-FDG PET/CT may be needed in aggressive tumours.
      In summary, F-DOPA PET/CT has widespread utility in the diagnosis of different
      neuroendocrine tumours. 

PMID- 25056983
TI  - Estimating population prevalence of potential airflow obstruction using different
      spirometric criteria: a pooled cross-sectional analysis of persons aged 40-95
      years in England and Wales.
AB  - OBJECTIVES: Consistent estimation of the burden of chronic obstructive pulmonary
      disease (COPD) has been hindered by differences in methods, including different
      spirometric cut-offs for impaired lung function. The impact of different
      definitions on the prevalence of potential airflow obstruction, and its
      associations with key risk factors, is evaluated using cross-sectional data from
      two nationally representative population surveys. DESIGN: Pooled cross-sectional
      analysis of Wave 2 of the UK Household Longitudinal Survey and the Health Survey
      for England 2010, including 7879 participants, aged 40-95 years, who lived in
      England and Wales, without diagnosed asthma and with good-quality spirometry
      data. Potential airflow obstruction was defined using self-reported physician
      diagnosed COPD; a fixed threshold (FT) forced expiratory volume in 1 s/forced
      vital capacity (FEV1/FVC) ratio <0.7 and an age-specific, sex-specific, height
      specific and ethnic-specific lower limit of normal (LLN). Standardised questions
      elicited self-reported information on demography, smoking history, ethnicity,
      occupation, respiratory symptoms and cardiovascular disease. RESULTS: Consistent
      across definitions, participants classed with obstructed airflow were more likely
      to be older, currently smoke, have higher pack-years of smoking and be engaged in
      routine occupations. The prevalence of airflow obstruction was 2.8% (95% CI 2.3%
      to 3.2%), 22.2% (21.2% to 23.2%) and 13.1% (12.2% to 13.9%) according to
      diagnosed COPD, FT and LLN, respectively. The gap in prevalence between FT and
      LLN increased in older age groups. Sex differences in the risk of obstruction,
      after adjustment for key risk factors, was sensitive to the choice of spirometric
      cut-off, being significantly higher in men when using FT, compared with no
      significant difference using LLN. CONCLUSIONS: Applying FT or LLN spirometric cut
      offs gives a different picture of the size and distribution of the disease
      burden. Longitudinal studies examining differences in unscheduled hospital
      admissions and risk of death between FT and LLN may inform the choice as to the
      best way to include spirometry in assessments of airflow obstruction.

PMID- 25056985
TI  - Why Lean doesn't work for everyone.
AB  - Popularisation of Lean in healthcare has led to emphasis on Lean quality
      improvement tools in isolation, with inconsistent results. We argue that delivery
      of safer, more efficient, and higher quality-patient focused care requires
      organisational transformation of which the Lean toolkit is only one component. To
      successfully facilitate system transformation toward higher quality care at lower
      cost, Lean tools must be part of a comprehensive management system, within a
      supportive institutional culture, and with committed leadership. 

PMID- 25056986
TI  - Association of periodontal status with occlusal force and food acceptability in
      70-year-old adults: from SONIC Study.
AB  - This cross-sectional study aimed to investigate the association of periodontal
      status with occlusal force and food acceptability. We hypothesised that
      mastication deteriorated with reduced periodontal support, even when posterior
      occlusal contacts with natural teeth were maintained and the patients remained
      clinically asymptomatic. Participants were 482 independently living 69-71-year
      olds, classified as Eichner's group A, having no mobile teeth and no periodontal
      symptoms. The periodontal probing depth (PPD) and restoration status of each
      tooth were examined. Occlusal force in the intercuspal position was measured with
      pressure-sensitive films. Food acceptability was evaluated from the difficulty
      experienced in chewing apples, grilled beef, and hard rice crackers. Multivariate
      regression analysis was performed to investigate the association of periodontal
      status with occlusal force and food acceptability. A P-value of <0.05 was
      considered statistically significant. Multiple linear regression analysis showed
      that occlusal force had significant negative associations with maximal PPD
      (standardised partial regression coefficient (beta) = -0.121) after controlling
      for gender, handgrip strength, number of teeth, and percentage of restored teeth.
      Approximately 15% of participants were included in the compromised food
      acceptability group. Logistic regression analyses showed that compromised food
      acceptability was significantly associated with PPD, after controlling for
      gender, number of teeth, and percentage of restored teeth. Periodontal probing
      depth (PPD) was significantly correlated with occlusal force and self-rated food
      acceptability after controlling for the possible confounding factors in
      septuagenarians, even those with complete posterior occlusal contacts and no
      tooth mobility.

PMID- 25056987
TI  - The effect of platelet-rich plasma on muscle contusion healing in a rat model.
AB  - BACKGROUND: Current therapy for muscle contusions is usually limited to
      nonsteroidal anti-inflammatory drugs and/or use of the RICE principle (rest, ice,
      compression, elevation); thus, other forms of treatment that can potentially
      accelerate the rate of healing are desirable. HYPOTHESES: A local injection of
      platelet-rich plasma (PRP) would lead to accelerated healing rates compared with
      controls; also, delayed administration of PRP would lead to a blunted response
      compared with immediate treatment. STUDY DESIGN: Controlled laboratory study.
      METHODS: Forty-six male Lewis rats each underwent a single blunt, nonpenetrating
      impact to the gastrocnemius muscle via a drop-mass technique and subsequently
      received either a single injection of saline into the area of injury immediately
      after injury (controls, n = 11) or rat PRP (either immediately after injury [PRP
      day 0, n = 12], the first day after injury [PRP day 1, n = 12], or the third day
      after injury [PRP day 3, n = 11]). The primary outcome was maximal isometric
      torque strength of the injured muscle, which was assessed before injury as well
      as on postinjury days 1, 4, 7, 10, and 14. All animals were sacrificed on
      postinjury day 15. Histological and immunohistochemical analyses were performed
      on 6 specimens from each group after sacrifice. RESULTS: The mean platelet
      concentration in the PRP was 2.19 * 10(6) (+/-2.69 * 10(5))/MUL. The mean white
      blood cell count in the PRP was 22.54 * 10(3)/MUL. Each group demonstrated
      statistically significant decreases in maximal isometric torque strength after
      injury when compared with preinjury levels, followed by significant increases
      back toward baseline values by postinjury day 14 (controls, 90.6% +/- 7.90%; PRP
      day 0, 105.0% +/- 7.60%; PRP day 1, 92.4% +/- 7.60%; PRP day 3, 77.8% +/- 7.90%)
      (P = .121). There were no statistically significant differences between the
      treatment and control groups at any of the time points. There were also no
      statistically significant differences between any of the groups in the percentage
      of centronucleated fibers (controls, 3.31% +/- 5.10%; PRP day 0, 0.62% +/- 1.59%;
      PRP day 1, 3.24% +/- 5.77%; PRP day 3, 2.13% +/- 3.26%) (P = .211) or the
      presence of inflammatory cells and macrophages. CONCLUSION: In this rat contusion
      model, a local injection of PRP into the injured gastrocnemius muscle resulted in
      no significant differences in functional or histological outcomes, indicating no
      likely benefit to healing. Additionally, there was no significant difference
      between immediate or delayed administration of PRP. CLINICAL RELEVANCE: Before
      PRP can be recommended for the treatment of muscle contusion injuries, further
      translational and clinical investigations need to be performed.

PMID- 25056988
TI  - Autologous chondrocyte implantation of the ankle: 2- to 10-year results.
AB  - BACKGROUND: The treatment of osteochondral lesions of the talus after failed
      surgery is challenging, with no clear solution. Short-term results using
      autologous chondrocyte implantation have been promising. PURPOSE: To report the
      long-term outcomes of patients who underwent autologous chondrocyte implantation
      (ACI) of the talus after failed marrow stimulation techniques for osteochondral
      lesions of the talus (OLTs). STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Thirty-two consecutive patients underwent ACI of the talus, and 29
      patients (15 male, 14 female; mean age, 34 years [range, 16-54 years]) were
      available for follow-up. There were 23 medial and 6 lateral lesions, with a mean
      size of 18 * 11 mm (198 mm(2); range, 80-500 mm(2)). Twenty patients underwent
      ACI of the talus alone; 9 underwent ACI with bone grafting of underlying cysts.
      Follow-up was performed at a mean of 70 months (range, 24-129 months). Patient
      outcomes were evaluated using the simplified symptomatology score, Tegner
      activity score, Finsen score, and American Orthopaedic Foot and Ankle Society
      (AOFAS) ankle-hindfoot score. Twenty-five patients (86%) underwent second-look
      arthroscopic surgery at the time of hardware removal and were assessed with the
      International Cartilage Repair Society (ICRS) score. Postoperative magnetic
      resonance imaging (MRI) was performed on 24 patients (83%) and compared with
      preoperative MRI scans. RESULTS: Preoperatively, 26 patients rated their ankles
      as poor and 3 as fair using the simplified symptomatology score. At last follow
      up, 9 were classified as excellent, 14 as good, 5 as fair, and 1 as poor using
      the same score. The mean AOFAS score improved from 50.1 to 85.9 (range, 65-100).
      The mean Tegner activity score improved from 1.6 to 4.3 (P < .0001). The mean
      Finsen score (modified Weber score) showed significant improvement from 13.7 to
      5.1 (P < .0001). CONCLUSION: Autologous chondrocyte implantation of the talus
      yields improvement in all parameters tested with enduring long-term results in
      patients who have failed previous surgery for OLTs.

PMID- 25056989
TI  - Acute achilles tendon ruptures: incidence of injury and surgery in Sweden between
      2001 and 2012.
AB  - BACKGROUND: Population-based incidence rates and trends of acute Achilles tendon
      ruptures are not known. It is also not known whether recent high-quality
      randomized controlled trials not favoring surgery have had an effect on treatment
      protocols. PURPOSE: To assess the incidence of acute Achilles tendon ruptures in
      Sweden and to examine the trends in surgical treatment. STUDY DESIGN: Descriptive
      epidemiology study. METHODS: We conducted a nationwide registry-based study
      including all adult (>=18 years of age) inpatient and outpatient hospital visits
      because of an acute Achilles tendon rupture in Sweden between 2001 and 2012.
      RESULTS: We identified a total of 27,702 patients (21,979 men, 79%) with acute
      Achilles tendon ruptures between 2001 and 2012. In 2001, the sex-specific
      incidence of acute Achilles tendon ruptures was 47.0 (per 100,000 person-years)
      in men and 12.0 in women. In 2012, the corresponding values were 55.2 in men and
      14.7 in women, with an increase of 17% in men and 22% in women. The proportion of
      surgically treated patients declined from 43% in 2001 to 28% in 2012 in men and
      from 34% in 2001 to 22% in 2012 in women. CONCLUSION: The incidence of acute
      Achilles tendon ruptures in Sweden is increasing. The most probable reason for
      this increase is the rise in the number of older adults participating in high
      demand sports. The proportion of surgically treated patients is decreasing most
      likely because of recent high-quality randomized controlled trials and their meta
      analyses supporting similar results between surgical and nonsurgical approaches.

PMID- 25056990
TI  - Does the femoral cam lesion regrow after osteoplasty for femoroacetabular
      impingement? Two-year follow-up.
AB  - BACKGROUND: There are currently no studies that have examined the recurrence of
      the cam lesion after femoral neck osteoplasty for femoroacetabular impingement.
      Although patient-reported outcome (PRO) scores at midterm follow-up have shown
      continued success, the maintenance of a normalized alpha angle has not been shown
      radiographically. PURPOSE: To assess the radiographic recurrence of cam deformity
      at 2-year follow-up after adequate decompression during the index hip
      arthroscopic procedure and correlate the findings with PRO scores. The hypothesis
      was that there would be no recurrence or regrowth of the cam deformity at the 2
      year postoperative time point after adequate cam decompression during hip
      arthroscopic surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Between March 2009 and January 2011, data were prospectively collected on all
      patients undergoing hip arthroscopic surgery with femoral neck osteoplasty.
      Minimum follow-up was 2 years, with radiographic images for review. RESULTS: A
      total of 47 patients met the inclusion criteria. The mean age of the participants
      at the start of the study was 37.18 years (range, 31.70-47.43 years). There were
      28 men (59.57%) and 19 women (40.43%). The mean follow-up duration was 28.32
      months (range, 24-41 months). The mean preoperative alpha angle (Dunn view) was
      70 degrees  (range, 60 degrees -97 degrees ), compared with 42.79 degrees 
      (range, 32 degrees -50 degrees ) at 2 weeks postoperatively (P < .0001). The mean
      2-year alpha angle was 42.72 degrees  (range, 32 degrees -54 degrees ), which was
      not significantly different compared with the mean 2-week alpha angle (P = .93).
      Additionally, the mean femoral offset measurement was 3.7 mm (range, 0-9.9 mm)
      preoperatively and 7.8 mm (range, 0.3-13.9 mm) 2 weeks postoperatively (P <
      .0001). The mean 2-year postoperative femoral offset measurement was 8.0 mm
      (range, 2.4-12.8 mm), which was not significantly different compared with the
      mean 2-week femoral offset measurement (P = .63). All PRO scores were
      significantly improved at 3 months compared with preoperative scores and, except
      for visual analog scale score, continued to show improvement at 2-year follow-up.
      CONCLUSION: There was no recurrence of cam deformity at 2 years after femoral
      neck osteoplasty for femoroacetabular impingement. PRO scores were improved at
      the 3-month and 2-year postoperative time points.

PMID- 25056991
TI  - Role of polymeric biomaterials as wound healing agents.
AB  - In uncontrolled hemorrhage, the main cause of death on the battlefield and in
      accidents, half of the deaths are caused by severe blood loss. Polymeric
      biomaterials have great potential in the control of severe hemorrhage from
      trauma, which is the second leading cause of death in the civilian community
      following central nervous system injuries. The intent of this article is to
      provide a review on currently available biopolymers used as wound dressing agents
      and to describe their best use as it relates to the condition and type of the
      wound (acute, chronic, superficial, and full thickness) and the phases of the
      wound healing process. These biopolymers are beneficial in tissue engineering as
      scaffolds, hydrogels, and films. Different types of wound dressings based on
      biopolymers are available in the market, with various physical, chemical, and
      biological properties. The use of biopolymers as a hemostatic agent depends on
      its biocompatibility, biodegradability, nonimmunogenicity, and optimal mechanical
      property. This review summarizes different biopolymers, their physiological
      characters, and their use as wound healing agents along with biomedical
      applications. 

PMID- 25056992
TI  - The prevalence of abnormal breathing patterns during exercise and associations
      with dynamic upper respiratory tract obstructions.
AB  - REASONS FOR PERFORMING STUDY: There is very limited published information on the
      prevalence and significance of abnormal breathing patterns adopted during
      canter/gallop. OBJECTIVES: The aim of this study was to report the prevalence of
      abnormal breathing patterns during canter/gallop and to investigate whether these
      may be associated with dynamic upper respiratory tract (URT) obstructions. STUDY
      DESIGN: Retrospective analysis of clinical records. METHODS: Simultaneous audio
      and URT videoendoscopy recordings from 365 horses referred for treadmill
      evaluation were analysed. RESULTS: Thirty percent of horses had an abnormal
      breathing pattern at canter or gallop, of which 23% had a 2:1 breathing pattern
      (i.e. one breath is taken over two strides). The prevalence of abnormal breathing
      patterns was higher at low canter speeds than during strenuous exercise. There
      was a significant association between breathing pattern during strenuous exercise
      and the presence of an URT obstruction. CONCLUSIONS: This study suggests that
      abnormal breathing patterns during canter and gallop may be associated with
      dynamic URT obstructions; therefore, horses identified by owners or veterinary
      surgeons to have an abnormal breathing pattern during exercise, in particular a
      2:1 breathing pattern, may warrant investigations for diagnosis of respiratory
      tract disease.

PMID- 25056993
TI  - Economic modeling of sealing primary molars using a "value of information"
      approach.
AB  - The objective was to evaluate 2 primary molar sealant strategies for publicly
      insured children using an "expected value of perfect information" (EVPI)
      approach. We converted a 10,000-observation tooth-level cost-effectiveness
      simulation model comparing 2 primary molar sealant strategies - always seal (AS)
      and standard care (SC) - with a 1,250-observation child-level model. Costs per
      child per restoration or extraction averted were estimated. Opportunity losses
      under the AS strategy were determined for children for whom SC was the optimal
      choice. We determined the EVPI by multiplying mean opportunity losses by the
      projected incident population of publicly insured 3-year-olds in the US over 10
      years with costs discounted at 2%. All analyses were conducted under assumptions
      of high and low intrachild correlations between at-risk teeth. The AS strategy
      cost $43.68 over SC (95% CI: -$5.50, $92.86) per child per restoration or
      extraction averted under the high intrachild correlation assumption and $15.54
      (95% CI $7.86, $23.20) under the low intrachild correlation. Under high
      intrachild correlation, mean opportunity losses were $80.28 (95% CI: $76.39,
      $84.17) per child, and AS was the optimal strategy in 31% of children. Under low
      correlation, mean opportunity losses were $14.61 (95% CI: $12.20, $17.68) and AS
      was the optimal strategy in 87% of children. The EVPI was calculated at
      $530,813,740 and $96,578,389 (for high and low intrachild correlation,
      respectively), for a projected total incident population of 8,059,712 children.
      On average, always sealing primary molars is more effective than standard care,
      but widespread implementation of this preventive approach among publicly insured
      children would result in large opportunity losses. Additional research is needed
      to identify the subgroups of publicly insured children who would benefit the most
      from this effective and potentially cost-saving public health intervention. 

PMID- 25056995
TI  - Restoring host-microbe homeostasis via selective chemoattraction of Tregs.
AB  - The disruption of host-microbe homeostasis at the site of periodontal disease is
      considered a key factor for disease initiation and progress. While the downstream
      mechanisms responsible for the tissue damage per se are relatively well-known
      (involving various patterns of immune response operating toward periodontal
      tissue destruction), we are only beginning to understand the complexity of host
      microbe interactions in the periodontal environment. Unfortunately, most of the
      research has been focused on the disruption of host-microbe homeostasis instead
      of focusing on the factors responsible for maintaining homeostasis. In this
      context, regulatory T-cells (Tregs) comprise a CD4+FOXp3 +T-cell subset with a
      unique ability to regulate other leukocyte functions to avoid excessive immune
      activation and its pathological consequences. Tregs act as critical determinants
      of host-microbe homeostasis, as well as determinants of a balanced host response
      after the disruption of host-microbe homeostasis by pathogens. In periodontitis,
      Tregs play a protective role, with their natural recruitment being responsible
      for conversion of active into inactive lesions. With controlled-release
      technology, it is now possible to achieve a selective chemoattraction of Tregs to
      periodontal tissues, attenuating experimental periodontitis evolution due to the
      local control of inflammatory immune response and the generation of a pro
      reparative environment. 

PMID- 25056994
TI  - Chronic periodontitis genome-wide association studies: gene-centric and gene set
      enrichment analyses.
AB  - Recent genome-wide association studies (GWAS) of chronic periodontitis (CP) offer
      rich data sources for the investigation of candidate genes, functional elements,
      and pathways. We used GWAS data of CP (n = 4,504) and periodontal pathogen
      colonization (n = 1,020) from a cohort of adult Americans of European descent
      participating in the Atherosclerosis Risk in Communities study and employed a
      MAGENTA approach (i.e., meta-analysis gene set enrichment of variant
      associations) to obtain gene-centric and gene set association results corrected
      for gene size, number of single-nucleotide polymorphisms, and local linkage
      disequilibrium characteristics based on the human genome build 18 (National
      Center for Biotechnology Information build 36). We used the Gene Ontology,
      Ingenuity, KEGG, Panther, Reactome, and Biocarta databases for gene set
      enrichment analyses. Six genes showed evidence of statistically significant
      association: 4 with severe CP (NIN, p = 1.6 * 10(-7); ABHD12B, p = 3.6 * 10(-7);
      WHAMM, p = 1.7 * 10(-6); AP3B2, p = 2.2 * 10(-6)) and 2 with high periodontal
      pathogen colonization (red complex-KCNK1, p = 3.4 * 10(-7); Porphyromonas
      gingivalis-DAB2IP, p = 1.0 * 10(-6)). Top-ranked genes for moderate CP were HGD
      (p = 1.4 * 10(-5)), ZNF675 (p = 1.5 * 10(-5)), TNFRSF10C (p = 2.0 * 10(-5)), and
      EMR1 (p = 2.0 * 10(-5)). Loci containing NIN, EMR1, KCNK1, and DAB2IP had showed
      suggestive evidence of association in the earlier single-nucleotide polymorphism
      based analyses, whereas WHAMM and AP2B2 emerged as novel candidates. The top gene
      sets included severe CP ("endoplasmic reticulum membrane," "cytochrome P450,"
      "microsome," and "oxidation reduction") and moderate CP ("regulation of gene
      expression," "zinc ion binding," "BMP signaling pathway," and "ruffle"). Gene
      centric analyses offer a promising avenue for efficient interrogation of large
      scale GWAS data. These results highlight genes in previously identified loci and
      new candidate genes and pathways possibly associated with CP, which will need to
      be validated via replication and mechanistic studies. 

PMID- 25056996
TI  - Israeli nurses' attitudes to the holistic approach to health and their use of
      complementary and alternative therapies.
AB  - PURPOSE: To examine nurses' attitudes to holistic and biomedical approaches to
      health care and the correlation between the two and to explore the extent of
      recommending and using complementary and alternative medicine (CAM) by nurses and
      its correlation with attitudes toward the holistic approach to care. DESIGN AND
      METHODS: In this cross-sectional correlational study, a structured questionnaire
      was completed anonymously by 213 Israeli hospital-based nurses from various
      departments. FINDINGS: Nurses perceived both approaches as critical to optimal
      health care: a positive correlation emerged of attitudes to the two approaches.
      Nurses recommended and used CAM extensively; most therapies were recommended
      and/or used by 70% or more of the respondents. Nurses with more positive
      attitudes toward holistic care tended to recommend and use CAM to a greater
      extent. CONCLUSIONS: Biomedical and holistic approaches are perceived by nurses
      to coexist within nursing professional boundaries and form a broad basis for
      optimal health care. Nurses' attitudes to the holistic approach appear to promote
      recommendation and/or use of CAM in practice. More training in CAM should be
      offered in nursing educational frameworks and research should continue to
      establish evidence for CAM's effectiveness.

PMID- 25056997
TI  - Diastereo- and enantioselective construction of a bispirooxindole scaffold
      containing a tetrahydro-beta-carboline moiety through an organocatalytic
      asymmetric cascade reaction.
AB  - The first catalytic asymmetric construction of a new class of bispirooxindole
      scaffold-containing tetrahydro-beta-carboline moiety has been established through
      chiral phosphoric acid-catalyzed three-component cascade Michael/Pictet-Spengler
      reactions of isatin-derived 3-indolylmethanols, isatins, and amino-ester, which
      afforded structurally complex and diverse bispirooxindoles with one quaternary
      and one tetrasubstituted stereogenic centers in excellent stereoselectivities
      (all >95:5 diastereomeric ratio (d.r.), up to 98:2 enantiomeric ratio (e.r.)).
      This intriguing class of chiral bispirooxindoles integrated the two important
      structures of tetrahydro-beta-carboline and bispirooxindole, both of them
      possessing significant bioactivities. This approach also combined the merits of
      asymmetric organocatalysis and multicomponent tandem reaction, which provided a
      unique strategy for the preparation of structurally rigid bispiro-architectures
      with concomitant creation of multiple quaternary stereogenic centers. 

PMID- 25056998
TI  - Determination of the absolute configuration of perylene quinone-derived
      mycotoxins by measurement and calculation of electronic circular dichroism
      spectra and specific rotations.
AB  - Altertoxins I-III, alterlosins I and II, alteichin (alterperylenol),
      stemphyltoxins I-IV, stemphyperylenol, stemphytriol, 7-epi-8-hydroxyaltertoxin I,
      and 6-epi-stemphytriol are mycotoxins derived from perylene quinone, for which
      the absolute configuration was not known. Electronic circular dichroism (ECD)
      spectra were calculated for these compounds and compared with measured spectra of
      altertoxins I-III, alteichin, and stemphyltoxin III and with reported Cotton
      effects. Specific rotations were calculated and compared with reported specific
      rotations. The absolute configuration of all the toxins, except for stemphyltoxin
      IV, could thus be determined. The validity of the assignment was high whenever
      reported ECD data were available for comparison, and the validity was lower when
      the assignment was based only on the comparison of calculated and reported
      specific rotations. ECD spectra are intrinsically different for toxins with a
      biphenyl substructure and for toxins derived from dihydroanthracene. 

PMID- 25056999
TI  - Improvement in balance using a virtual reality-based stepping exercise: a
      randomized controlled trial involving individuals with chronic stroke.
AB  - OBJECTIVE: To study the clinical effectiveness and the usability of a virtual
      reality-based intervention compared with conventional physical therapy in the
      balance recovery of individuals with chronic stroke. DESIGN: Randomized
      controlled trial. SETTING: Outpatient neurorehabilitation unit. PARTICIPANTS: A
      total of 20 individuals with chronic stroke. INTERVENTIONS: The intervention
      consisted of 20 one-hour sessions, five sessions per week. The experimental group
      combined 30 minutes with the virtual reality-based intervention with 30 minutes
      of conventional training. The control group underwent one hour conventional
      therapy. MAIN MEASURES: Balance performance was assessed at the beginning and at
      the end of the trial using the Berg Balance Scale, the balance and gait subscales
      of the Tinetti Performance-Oriented Mobility Assessment, the Brunel Balance
      Assessment, and the 10-m Walking Test. Subjective data of the virtual reality
      based intervention were collected from the experimental group, with a feedback
      questionnaire at the end of the trial. RESULTS: The results revealed a
      significant group-by-time interaction in the scores of the Berg Balance Scale (p
      < 0.05) and in the 10-m Walking Test (p < 0.05). Post-hoc analyses showed greater
      improvement in the experimental group: 3.8 +/-2.6 vs. 1.8 +/-1.4 in the Berg
      Balance Scale, -1.9 +/-1.6 seconds vs. 0.0 +/-2.3 seconds in the 10-m Walking
      Test, and also in the number of participants who increased level in the Brunel
      Balance Assessment (chi(2) = 2.5, p < 0.01). CONCLUSIONS: Virtual reality
      interventions can be an effective resource to enhance the improvement of balance
      in individuals with chronic stroke.

PMID- 25057000
TI  - The development and implementation of the structured training programme for
      caregivers of inpatients after stroke (TRACS) intervention: the London Stroke
      Carers Training Course.
AB  - OBJECTIVE: To describe the content and delivery of the adapted London Stroke
      Carers Training Course intervention evaluated in the Training Caregivers after
      Stroke (TRACS) trial. SETTING: The London Stroke Carers Training Course is a
      structured training programme for caregivers of inpatients who are likely to
      return home after their stroke. The course was delivered by members of the
      multidisciplinary team while the patient was in the stroke unit with one
      recommended 'follow through' session after discharge home. INTERVENTION: The
      intervention consists of 14 training components (six mandatory) that were
      identified as important knowledge/skills that caregivers would need to be able to
      care for the stroke patient after discharge home. Following national training
      days, the London Stroke Carers Training Course was disseminated to intervention
      sites by the cascade method of implementation. RESULTS: The intervention was
      adapted for implementation across a range of stroke units. Training days were
      well attended (median 2.5 and 2.0 attendees per centre for the first and second
      days, respectively) and the feedback positive, demonstrating 'face validity' for
      the intervention. However cascading of this training to other members of the
      multidisciplinary team was not consistent, with 7/18 centres recording no cascade
      training. CONCLUSION: The adapted London Stroke Carers Training Course provided a
      training programme that could be delivered in a standardised, structured way in a
      variety of stroke unit settings throughout the UK. The intervention was well
      received by stroke unit staff, however, the cascade method of implementation was
      not as effective as we would have wished.

PMID- 25057001
TI  - Standardization of health care provider competencies for intrathecal access
      procedures.
AB  - INTRODUCTION: This quality improvement (QI) project addresses a method for
      experienced health care providers to maintain skill-based competence for
      intrathecal access procedures. METHODS: A prospective QI design using intrathecal
      access simulation to assess, educate, and evaluate skill competency. Simulation
      was used as a strategy to promote patient safety and standardize practice
      patterns. Pretest and posttest methodology using paired t tests were performed to
      assess anxiety, confidence, and knowledge. RESULTS: Fourteen pediatric providers
      participated in this QI project. There was a statistically significant
      improvement in confidence measuring intracranial pressure (ICP; t = -2.92, P =
      .013), performance-related overall anxiety (t = -2.132, P = .05) and
      administering intrathecal chemotherapy (t = -2.144, P = .053). Fifty percent of
      participants missed a medication error demonstrating confirmation bias.
      CONCLUSION: This simulation strategy resulted in improved confidence in measuring
      ICP, performance-related overall anxiety, and confidence in administering
      chemotherapy. Confirmation bias occurred during simulation testing for a
      medication error. We propose this method for maintaining clinical competencies in
      health care providers and introducing new skills to existing practices.

PMID- 25057002
TI  - Psychometric properties of the oncology module of the KINDL scale: first results.
AB  - PURPOSE: The objective of this study was to assess the reliability and validity
      of the Oncology module of the generic KINDL scale (having 24 items with 6
      domains). METHODS: The psychometric properties of the KINDL Oncology module were
      evaluated from the aspect of internal consistency, reliability, and construct
      validity on an inpatient sample of 103 Turkish children (mean age 10.0 +/- 4.01
      years) who had various oncological disorders. RESULTS: The KINDL Oncology module
      (24 items) showed acceptable alpha coefficients ranging from .57 (physical well
      being) to .87 (treatment) for each domain. In confirmatory factor analysis of the
      original 4-domain structure, Root Mean Square Error of Approximation was found as
      .086, and Comparative Fit Index was .87. Good known groups results supported the
      construct validity of the instrument. Correlations between the domains of the
      mother KINDL and the domains of its oncology module were significantly high,
      indicating a satisfactory convergent validity. CONCLUSION: The Turkish version of
      the KINDL Oncology module showed good reliability and questionable validity in
      this study. However, further research on other language versions of the module is
      needed for its global use.

PMID- 25057004
TI  - CD326(lo)CD103(lo)CD11b(lo) dermal dendritic cells are activated by thymic
      stromal lymphopoietin during contact sensitization in mice.
AB  - The cytokine thymic stromal lymphopoietin (TSLP) is produced by epithelia exposed
      to the contact sensitizer dibutyl phthalate (DBP), and it is critical for the
      induction of Th2 immune responses by DBP-FITC. TSLP is thought to act on
      dendritic cells (DC), but the precise DC subsets involved in the response to TSLP
      remain to be fully characterized. In this study we show that a subset of
      CD326(lo)CD103(lo)CD11b(lo) dermal DC, which we termed "triple-negative (TN) DC,"
      is highly responsive to TSLP. In DBP-FITC-treated mice, TN DC upregulated
      expression of CD86 and rapidly migrated to the draining lymph node to become the
      most abundant skin-derived DC subset at 24 and 48 h after sensitization. None of
      these responses was observed in TSLPR-deficient mice. In contrast, TN DC numbers
      were not increased after treatment with the allergen house dust mite or the
      bacteria Escherichia coli and bacillus Calmette-Guerin, which increased other DC
      subsets. In vivo, treatment with rTSLP preferentially increased the numbers of TN
      DC in lymph nodes. In vitro, TN DC responded to rTSLP treatment with a higher
      level of STAT5 phosphorylation compared with other skin-derived DC subsets. The
      TN DC subset shared the morphology, phenotype, and developmental requirements of
      conventional DC, depending on FLT3 expression for their optimal development from
      bone marrow precursors, and CCR7 for migration to the draining lymph node. Thus,
      TN DC represent a dermal DC subset that should be considered in future studies of
      TSLP-dependent contact sensitization and skin immune responses. 

PMID- 25057003
TI  - Modulation of TNF-induced macrophage polarization by synovial fibroblasts.
AB  - Mesenchymal stromal cells have emerged as powerful modulators of the immune
      system. In this study, we explored how the human macrophage response to TNF is
      regulated by human synovial fibroblasts, the representative stromal cell type in
      the synovial lining of joints that become activated during inflammatory
      arthritis. We found that synovial fibroblasts strongly suppressed TNF-mediated
      induction of an IFN-beta autocrine loop and downstream expression of IFN
      stimulated genes (ISGs), including chemokines CXCL9 and CXCL10 that are
      characteristic of classical macrophage activation. TNF induced the production of
      soluble synovial fibroblast factors that suppressed the macrophage production of
      IFN-beta, and cooperated with TNF to limit the responsiveness of macrophages to
      IFN-beta by suppressing activation of Jak-STAT signaling. Genome-wide
      transcriptome analysis showed that cocultured synovial fibroblasts modulate the
      expression of approximately one third of TNF-regulated genes in macrophages,
      including genes in pathways important for macrophage survival and polarization
      toward an alternatively activated phenotype. Pathway analysis revealed that gene
      expression programs regulated by synovial fibroblasts in our coculture system
      were also regulated in rheumatoid arthritis synovial macrophages, suggesting that
      these fibroblast-mediated changes may contribute to rheumatoid arthritis
      pathogenesis. This work furthers our understanding of the interplay between
      innate immune and stromal cells during an inflammatory response, one that is
      particularly relevant to inflammatory arthritis. Our findings also identify
      modulation of macrophage phenotype as a new function for synovial fibroblasts
      that may prove to be a contributing factor in arthritis pathogenesis. 

PMID- 25057005
TI  - Laser ablation-inductively coupled plasma mass spectrometry: an emerging
      technology for detecting rare cells in tissue sections.
AB  - Administering immunoregulatory cells to patients as medicinal agents is a
      potentially revolutionary approach to the treatment of immunologically mediated
      diseases. Presently, there are no satisfactory, clinically applicable methods of
      tracking human cells in patients with adequate spatial resolution and target cell
      specificity over a sufficient period of time. Laser ablation-inductively coupled
      plasma mass spectrometry (LA-ICP-MS) represents a potential solution to the
      problem of detecting very rare cells in tissues. In this article, this
      exquisitely sensitive technique is applied to the tracking of gold-labeled human
      regulatory macrophages (Mregs) in immunodeficient mice. Optimal conditions for
      labeling Mregs with 50-nm gold particles were investigated by exposing Mregs in
      culture to variable concentrations of label: Mregs incubated with 3.5 * 10(9)
      particles/ml for 1 h incorporated an average of 3.39 * 10(8) Au atoms/cell
      without loss of cell viability. Analysis of single, gold-labeled Mregs by LA-ICP
      MS registered an average of 1.9 * 10(5) counts/cell. Under these conditions, 100%
      labeling efficiency was achieved, and label was retained by Mregs for >=36 h.
      Gold-labeled Mregs adhered to glass surfaces; after 24 h of culture, it was
      possible to colabel these cells with human-specific (154)Sm-tagged anti-HLA-DR or
      (174)Yb-tagged anti-CD45 mAbs. Following injection into immunodeficient mice,
      signals from gold-labeled human Mregs could be detected in mouse lung, liver, and
      spleen for at least 7 d by solution-based inductively coupled plasma mass
      spectrometry and LA-ICP-MS. These promising results indicate that LA-ICP-MS
      tissue imaging has great potential as an analytical technique in immunology. 

PMID- 25057006
TI  - Differential requirement for the IKKbeta/NF-kappaB signaling module in regulating
      TLR- versus RLR-induced type 1 IFN expression in dendritic cells.
AB  - Host innate-immune responses are tailored by cell type to control and eradicate
      specific infectious agents. For example, an acute RNA virus infection can result
      in high-level expression of type 1 IFNs by both conventional dendritic cells
      (cDCs) and plasmacytoid dendritic cells (pDCs), but whereas cDCs preferentially
      use RIG-I-like receptor (RLR) signaling to produce type 1 IFNs, pDCs
      predominantly use TLRs to induce these cytokines. We previously found that the
      IkappaB kinase beta (IKKbeta)/NF-kappaB pathway regulates early IFN-beta
      expression, but not the magnitude of type 1 IFN expression following RLR
      engagement. In this study, we use IKKbeta inhibition and mice deficient in
      IKKbeta or canonical NF-kappaB subunits (p50, RelA/p65, and cRel) to demonstrate
      that the IKKbeta/NF-kappaB axis is critical for virus-induced type 1 IFN
      expression in pDCs, but not in cDCs. We also reveal a crucial and more general
      requirement for IKKbeta/NF-kappaB in TLR- but not RLR-induced expression of type
      1 IFNs and inflammatory cytokines. Together, these findings reveal a previously
      unappreciated specificity of the IKKbeta/NF-kappaB signaling axis in regulation
      of antimicrobial responses by different classes of pattern recognition receptors,
      and therefore by individual cell types reliant on particular pattern recognition
      receptors for their innate-immune transcriptional responses. 

PMID- 25057007
TI  - Macrophage- and neutrophil-derived TNF-alpha instructs skin langerhans cells to
      prime antiviral immune responses.
AB  - Dendritic cells are major APCs that can efficiently prime immune responses.
      However, the roles of skin-resident Langerhans cells (LCs) in eliciting immune
      responses have not been fully understood. In this study, we demonstrate for the
      first time, to our knowledge, that LCs in cynomolgus macaque skin are capable of
      inducing antiviral-specific immune responses in vivo. Targeting HIV-Gag or
      influenza hemagglutinin Ags to skin LCs using recombinant fusion proteins of anti
      Langerin Ab and Ags resulted in the induction of the viral Ag-specific responses.
      We further demonstrated that such Ag-specific immune responses elicited by skin
      LCs were greatly enhanced by TLR ligands, polyriboinosinic polyribocytidylic
      acid, and R848. These enhancements were not due to the direct actions of TLR
      ligands on LCs, but mainly dependent on TNF-alpha secreted from macrophages and
      neutrophils recruited to local tissues. Skin LC activation and migration out of
      the epidermis are associated with macrophage and neutrophil infiltration into the
      tissues. More importantly, blocking TNF-alpha abrogated the activation and
      migration of skin LCs. This study highlights that the cross-talk between innate
      immune cells in local tissues is an important component for the establishment of
      adaptive immunity. Understanding the importance of local immune networks will
      help us to design new and effective vaccines against microbial pathogens. 

PMID- 25057008
TI  - Myeloid-derived suppressor cells as a potential therapy for experimental
      autoimmune myasthenia gravis.
AB  - We recently demonstrated that hepatic stellate cells induce the differentiation
      of myeloid-derived suppressor cells (MDSCs) from myeloid progenitors. In this
      study, we found that adoptive transfer of these MDSCs effectively reversed
      disease progression in experimental autoimmune myasthenia gravis (EAMG), a T cell
      dependent and B cell-mediated model for myasthenia gravis. In addition to
      ameliorated disease severity, MDSC-treated EAMG mice showed suppressed
      acetylcholine receptor (AChR)-specific T cell responses, decreased levels of
      serum anti-AChR IgGs, and reduced complement activation at the neuromuscular
      junctions. Incubating MDSCs with B cells activated by anti-IgM or anti-CD40 Abs
      inhibited the proliferation of these in vitro-activated B cells. Administering
      MDSCs into mice immunized with a T cell-independent Ag inhibited the Ag-specific
      Ab production in vivo. MDSCs directly inhibit B cells through multiple
      mechanisms, including PGE2, inducible NO synthase, and arginase. Interestingly,
      MDSC treatment in EAMG mice does not appear to significantly inhibit their immune
      response to a nonrelevant Ag, OVA. These results demonstrated that hepatic
      stellate cell-induced MDSCs concurrently suppress both T and B cell autoimmunity,
      leading to effective treatment of established EAMG, and that the MDSCs inhibit
      AChR-specific immune responses at least partially in an Ag-specific manner. These
      data suggest that MDSCs could be further developed as a novel approach to
      treating myasthenia gravis and, even more broadly, other diseases in which T and
      B cells are involved in pathogenesis. 

PMID- 25057009
TI  - Zfp318 regulates IgD expression by abrogating transcription termination within
      the Ighm/Ighd locus.
AB  - The protein Zfp318 is expressed during the transition of naive B cells from an
      immature to mature state. To evaluate its role in mature B cell functions, a
      conditional gene deficiency in Zfp318 was created and deleted in bone marrow
      lineages via Vav-Cre. B cell development was minimally altered in the absence of
      the protein, although transitional 2 (T2) B cell populations were depressed in
      the absence of Zfp318. Intriguingly, the analysis of IgM and IgD expression by
      maturing and mature naive B cells demonstrated an elevated level of IgM gene
      products and a virtual loss of IgD products. Transcriptome analysis of Zfp318
      deficient B cells revealed that only two gene products showed altered expression
      in the absence of Zfp318 (Ighd and Sva), demonstrating a remarkable specificity
      of Zfp318 action. In the absence of Zfp318, Ighm/Ighd transcripts, which would
      normally encode IgM and IgD from heterogeneous nuclear RNA transcripts via
      alternative splicing, lack intron and exon sequences from the IgD (Ighd)-encoding
      region. This finding indicates that Zfp318, in a novel manner, functions by
      repressing recognition of the transcriptional termination site at the 3' end of
      the terminal IgM-encoding exon, allowing for synthesis of the complete Ighm/Ighd
      heterogeneous nuclear RNA. 

PMID- 25057010
TI  - Pressure and volume controlled mechanical ventilation in anaesthetized pregnant
      sheep.
AB  - Optimal mechanical ventilation of the pregnant ewe during anaesthesia is of vital
      importance for maintaining fetal viability. This study aimed to compare peak
      inspiratory pressure (PIP), oxygenation and cardiovascular parameters with
      pressure-control (PCV) or volume-control (VCV) mechanical ventilation of
      anaesthetized pregnant sheep. Twenty ewes at 110 days gestation underwent general
      anaesthesia in dorsal recumbency for fetal surgery in a research setting. All the
      sheep were mechanically ventilated; one group with PCV (n = 10) and another with
      VCV (n = 10) to maintain normocapnia. PIP, direct arterial blood pressure, heart
      rate, arterial pH and arterial oxygen tension were recorded. PIP was lower in the
      PCV group (P < 0.001). Arterial oxygen tension was higher in the PCV group (P =
      0.013). Mean and diastolic pressures were lower in the PCV group (P = 0.029 and P
      = 0.047, respectively). Both VCV and PCV provide adequate oxygenation of pregnant
      sheep anaesthetized in dorsal recumbency, though PCV may provide superior
      oxygenation at a lower PIP.

PMID- 25057011
TI  - Nuclear factor of activated T-cells 5 increases intestinal goblet cell
      differentiation through an mTOR/Notch signaling pathway.
AB  - The intestinal mucosa undergoes a continual process of proliferation,
      differentiation, and apoptosis that is regulated by multiple signaling pathways.
      Previously, we have shown that the nuclear factor of activated T-cells 5 (NFAT5)
      is involved in the regulation of intestinal enterocyte differentiation. Here we
      show that treatment with sodium chloride (NaCl), which activates NFAT5 signaling,
      increased mTORC1 repressor regulated in development and DNA damage response 1
      (REDD1) protein expression and inhibited mTOR signaling; these alterations were
      attenuated by knockdown of NFAT5. Knockdown of NFAT5 activated mammalian target
      of rapamycin (mTOR) signaling and significantly inhibited REDD1 mRNA expression
      and protein expression. Consistently, overexpression of NFAT5 increased REDD1
      expression. In addition, knockdown of REDD1 activated mTOR and Notch signaling,
      whereas treatment with mTOR inhibitor rapamycin repressed Notch signaling and
      increased the expression of the goblet cell differentiation marker mucin 2
      (MUC2). Moreover, knockdown of NFAT5 activated Notch signaling and decreased MUC2
      expression, while overexpression of NFAT5 inhibited Notch signaling and increased
      MUC2 expression. Our results demonstrate a role for NFAT5 in the regulation of
      mTOR signaling in intestinal cells. Importantly, these data suggest that NFAT5
      participates in the regulation of intestinal homeostasis via the suppression of
      mTORC1/Notch signaling pathway. 

PMID- 25057012
TI  - The Caenorhabditis elegans SUN protein UNC-84 interacts with lamin to transfer
      forces from the cytoplasm to the nucleoskeleton during nuclear migration.
AB  - Nuclear migration is a critical component of many cellular and developmental
      processes. The nuclear envelope forms a barrier between the cytoplasm, where
      mechanical forces are generated, and the nucleoskeleton. The LINC complex
      consists of KASH proteins in the outer nuclear membrane and SUN proteins in the
      inner nuclear membrane that bridge the nuclear envelope. How forces are
      transferred from the LINC complex to the nucleoskeleton is poorly understood. The
      Caenorhabditis elegans lamin, LMN-1, is required for nuclear migration and
      interacts with the nucleoplasmic domain of the SUN protein UNC-84. This
      interaction is weakened by the unc-84(P91S) missense mutation. These mutant
      nuclei have an intermediate nuclear migration defect-live imaging of nuclei or
      LMN-1::GFP shows that many nuclei migrate normally, others initiate migration
      before subsequently failing, and others fail to begin migration. At least one
      other component of the nucleoskeleton, the NET5/Samp1/Ima1 homologue SAMP-1,
      plays a role in nuclear migration. We propose a nut-and-bolt model to explain how
      forces are dissipated across the nuclear envelope during nuclear migration. In
      this model, SUN/KASH bridges serve as bolts through the nuclear envelope, and
      nucleoskeleton components LMN-1 and SAMP-1 act as both nuts and washers on the
      inside of the nucleus. 

PMID- 25057013
TI  - A role for eisosomes in maintenance of plasma membrane phosphoinositide levels.
AB  - The plasma membrane delineates the cell and mediates its communication and
      material exchange with the environment. Many processes of the plasma membrane
      occur through interactions of proteins with phosphatidylinositol(4,5)
      bisphosphate (PI(4,5)P2), which is highly enriched in this membrane and is a key
      determinant of its identity. Eisosomes function in lateral organization of the
      plasma membrane, but the molecular function of their major protein subunits, the
      BAR domain-containing proteins Pil1 and Lsp1, is poorly understood. Here we show
      that eisosomes interact with the PI(4,5)P2 phosphatase Inp51/Sjl1, thereby
      recruiting it to the plasma membrane. Pil1 is essential for plasma membrane
      localization and function of Inp51 but not for the homologous
      phosphatidylinositol bisphosphate phosphatases Inp52/Sjl2 and Inp53/Sjl3.
      Consistent with this, absence of Pil1 increases total and available PI(4,5)P2
      levels at the plasma membrane. On the basis of these findings, we propose a model
      in which the eisosomes function in maintaining PI(4,5)P2 levels by Inp51/Sjl1
      recruitment. 

PMID- 25057014
TI  - Mad2, Bub3, and Mps1 regulate chromosome segregation and mitotic synchrony in
      Giardia intestinalis, a binucleate protist lacking an anaphase-promoting complex.
AB  - The binucleate pathogen Giardia intestinalis is a highly divergent eukaryote with
      a semiopen mitosis, lacking an anaphase-promoting complex/cyclosome (APC/C) and
      many of the mitotic checkpoint complex (MCC) proteins. However, Giardia has some
      MCC components (Bub3, Mad2, and Mps1) and proteins from the cohesin system (Smc1
      and Smc3). Mad2 localizes to the cytoplasm, but Bub3 and Mps1 are either located
      on chromosomes or in the cytoplasm, depending on the cell cycle stage. Depletion
      of Bub3, Mad2, or Mps1 resulted in a lowered mitotic index, errors in chromosome
      segregation (including lagging chromosomes), and abnormalities in spindle
      morphology. During interphase, MCC knockdown cells have an abnormal number of
      nuclei, either one nucleus usually on the left-hand side of the cell or two
      nuclei with one mislocalized. These results suggest that the minimal set of MCC
      proteins in Giardia play a major role in regulating many aspects of mitosis,
      including chromosome segregation, coordination of mitosis between the two nuclei,
      and subsequent nuclear positioning. The critical importance of MCC proteins in an
      organism that lacks their canonical target, the APC/C, suggests a broader role
      for these proteins and hints at new pathways to be discovered. 

PMID- 25057015
TI  - A separable domain of the p150 subunit of human chromatin assembly factor-1
      promotes protein and chromosome associations with nucleoli.
AB  - Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved
      throughout eukaryotes that deposits histones during DNA synthesis. Here we
      present a novel role for the human p150 subunit in regulating nucleolar
      macromolecular interactions. Acute depletion of p150 causes redistribution of
      multiple nucleolar proteins and reduces nucleolar association with several
      repetitive element-containing loci. Of note, a point mutation in a SUMO
      interacting motif (SIM) within p150 abolishes nucleolar associations, whereas
      PCNA or HP1 interaction sites within p150 are not required for these
      interactions. In addition, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9
      reduces alpha-satellite DNA association with nucleoli. The nucleolar functions of
      p150 are separable from its interactions with the other subunits of the CAF-1
      complex because an N-terminal fragment of p150 (p150N) that cannot interact with
      other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and
      protein associations. Therefore these data define novel functions for a separable
      domain of the p150 protein, regulating protein and DNA interactions at the
      nucleolus. 

PMID- 25057016
TI  - Csi1p recruits alp7p/TACC to the spindle pole bodies for bipolar spindle
      formation.
AB  - Accurate chromosome segregation requires timely bipolar spindle formation during
      mitosis. The transforming acidic coiled-coil (TACC) family proteins and the ch
      TOG family proteins are key players in bipolar spindle formation. They form a
      complex to stabilize spindle microtubules, mainly dependent on their localization
      to the centrosome (the spindle pole body [SPB] in yeast). The molecular mechanism
      underlying the targeting of the TACC-ch-TOG complex to the centrosome remains
      unclear. Here we show that the fission yeast Schizosaccharomyces pombe TACC
      orthologue alp7p is recruited to the SPB by csi1p. The csi1p-interacting region
      lies within the conserved TACC domain of alp7p, and the carboxyl-terminal domain
      of csi1p is responsible for interacting with alp7p. Compromised interaction
      between csi1p and alp7p impairs the localization of alp7p to the SPB during
      mitosis, thus delaying bipolar spindle formation and leading to anaphase B
      lagging chromosomes. Hence our study establishes that csi1p serves as a linking
      molecule tethering spindle-stabilizing factors to the SPB for promoting bipolar
      spindle assembly. 

PMID- 25057017
TI  - Med13p prevents mitochondrial fission and programmed cell death in yeast through
      nuclear retention of cyclin C.
AB  - The yeast cyclin C-Cdk8 kinase forms a complex with Med13p to repress the
      transcription of genes involved in the stress response and meiosis. In response
      to oxidative stress, cyclin C displays nuclear to cytoplasmic relocalization that
      triggers mitochondrial fission and promotes programmed cell death. In this
      report, we demonstrate that Med13p mediates cyclin C nuclear retention in
      unstressed cells. Deleting MED13 allows aberrant cytoplasmic cyclin C
      localization and extensive mitochondrial fragmentation. Loss of Med13p function
      resulted in mitochondrial dysfunction and hypersensitivity to oxidative stress
      induced programmed cell death that were dependent on cyclin C. The regulatory
      system controlling cyclin C-Med13p interaction is complex. First, a previous
      study found that cyclin C phosphorylation by the stress-activated MAP kinase
      Slt2p is required for nuclear to cytoplasmic translocation. This study found that
      cyclin C-Med13p association is impaired when the Slt2p target residue is
      substituted with a phosphomimetic amino acid. The second step involves Med13p
      destruction mediated by the 26S proteasome and cyclin C-Cdk8p kinase activity. In
      conclusion, Med13p maintains mitochondrial structure, function, and normal
      oxidative stress sensitivity through cyclin C nuclear retention. Releasing cyclin
      C from the nucleus involves both its phosphorylation by Slt2p coupled with Med13p
      destruction. 

PMID- 25057019
TI  - A lysine deacetylase Hos3 is targeted to the bud neck and involved in the spindle
      position checkpoint.
AB  - An increasing number of cellular activities can be regulated by reversible lysine
      acetylation. Targeting the enzymes responsible for such posttranslational
      modifications is instrumental in defining their substrates and functions in vivo.
      Here we show that a Saccharomyces cerevisiae lysine deacetylase, Hos3, is
      asymmetrically targeted to the daughter side of the bud neck and to the daughter
      spindle pole body (SPB). The morphogenesis checkpoint member Hsl7 recruits Hos3
      to the neck region. Cells with a defect in spindle orientation trigger Hos3 to
      load onto both SPBs. When associated symmetrically with both SPBs, Hos3 functions
      as a spindle position checkpoint (SPOC) component to inhibit mitotic exit. Neck
      localization of Hos3 is essential for its symmetric association with SPBs in
      cells with misaligned spindles. Our data suggest that Hos3 facilitates cross-talk
      between the morphogenesis checkpoint and the SPOC as a component of the intricate
      monitoring of spindle orientation after mitotic entry and before commitment to
      mitotic exit. 

PMID- 25057018
TI  - The ARF tumor suppressor prevents chromosomal instability and ensures mitotic
      checkpoint fidelity through regulation of Aurora B.
AB  - The ARF tumor suppressor is part of the CDKN2A locus and is mutated or
      undetectable in numerous cancers. The best-characterized role for ARF is in
      stabilizing p53 in response to cellular stress. However, ARF has tumor
      suppressive functions outside this pathway that have not been fully defined.
      Primary mouse embryonic fibroblasts (MEFs) lacking the ARF tumor suppressor
      contain abnormal numbers of chromosomes. However, no role for ARF in cell
      division has previously been proposed. Here we demonstrate a novel, p53
      independent role for ARF in the mitotic checkpoint. Consistent with this, loss of
      ARF results in aneuploidy in vitro and in vivo. ARF(-/-) MEFs exhibit mitotic
      defects including misaligned and lagging chromosomes, multipolar spindles, and
      increased tetraploidy. ARF(-/-) cells exhibit overexpression of Mad2, BubR1, and
      Aurora B, but only overexpression of Aurora B phenocopies mitotic defects
      observed in ARF(-/-) MEFs. Restoring Aurora B to near-normal levels rescues
      mitotic phenotypes in cells lacking ARF. Our results define an unexpected role
      for ARF in chromosome segregation and mitotic checkpoint function. They further
      establish maintenance of chromosomal stability as one of the additional tumor
      suppressive functions of ARF and offer a molecular explanation for the common up
      regulation of Aurora B in human cancers. 

PMID- 25057020
TI  - A novel pathway of rapid TLR-triggered activation of integrin-dependent leukocyte
      adhesion that requires Rap1 GTPase.
AB  - Rapid beta2-integrin activation is indispensable for leukocyte adhesion and
      recruitment to sites of infection and is mediated by chemokine- or P-selectin
      glycoprotein ligand-1-induced inside-out signaling. Here we uncovered a novel
      pathway for rapid activation of integrin-dependent leukocyte adhesion, triggered
      by toll-like receptor (TLR)-mediated signaling. TLR2 or TLR5 ligation rapidly
      activated integrin-dependent leukocyte adhesion to immobilized ICAM-1 and
      fibronectin. Consistently, in vivo administration of the TLR2-ligand Pam3CSK4
      increased integrin-dependent slow rolling and adhesion to endothelium within
      minutes, as identified by intravital microscopy in the cremaster model. TLR2 and
      TLR5 ligation increased beta2-integrin affinity, as assessed by the detection of
      activation-dependent neoepitopes. TLR2- and TLR5-triggered integrin activation in
      leukocytes required enhanced Rap1 GTPase activity, which was mediated by Rac1
      activation and NADPH oxidase-2-dependent reactive oxygen species production. This
      novel direct pathway linking initial pathogen recognition by TLRs to rapid beta2
      integrin activation may critically regulate acute leukocyte infiltration to sites
      of pathogen invasion. 

PMID- 25057021
TI  - Molecular dissection of the mechanism by which EWS/FLI expression compromises
      actin cytoskeletal integrity and cell adhesion in Ewing sarcoma.
AB  - Ewing sarcoma is the second-most-common bone cancer in children. Driven by an
      oncogenic chromosomal translocation that results in the expression of an aberrant
      transcription factor, EWS/FLI, the disease is typically aggressive and
      micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor
      cells results in the altered expression of hundreds to thousands of genes and is
      accompanied by dramatic morphological changes in cytoarchitecture and adhesion.
      Genes encoding focal adhesion, extracellular matrix, and actin regulatory
      proteins are dominant targets of EWS/FLI-mediated transcriptional repression.
      Reexpression of genes encoding just two of these proteins, zyxin and alpha5
      integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity
      comparable to what is observed when the EWS/FLI oncogene expression is
      compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced
      repression of alpha5 integrin and zyxin expression promotes tumor progression by
      supporting anchorage-independent cell growth. This selective advantage is paired
      with a tradeoff in which metastatic lung colonization is compromised. 

PMID- 25057022
TI  - Separate responses of karyopherins to glucose and amino acid availability
      regulate nucleocytoplasmic transport.
AB  - The importin-beta family members (karyopherins) mediate the majority of
      nucleocytoplasmic transport. Msn5 and Los1, members of the importin-beta family,
      function in tRNA nuclear export. tRNAs move bidirectionally between the nucleus
      and the cytoplasm. Nuclear tRNA accumulation occurs upon amino acid (aa) or
      glucose deprivation. To understand the mechanisms regulating tRNA subcellular
      trafficking, we investigated whether Msn5 and Los1 are regulated in response to
      nutrient availability. We provide evidence that tRNA subcellular trafficking is
      regulated by distinct aa-sensitive and glucose-sensitive mechanisms. Subcellular
      distributions of Msn5 and Los1 are altered upon glucose deprivation but not aa
      deprivation. Redistribution of tRNA exportins from the nucleus to the cytoplasm
      likely provides one mechanism for tRNA nuclear distribution upon glucose
      deprivation. We extended our studies to other members of the importin-beta family
      and found that all tested karyopherins invert their subcellular distributions
      upon glucose deprivation but not aa deprivation. Glucose availability regulates
      the subcellular distributions of karyopherins likely due to alteration of the
      RanGTP gradient since glucose deprivation causes redistribution of Ran. Thus
      nuclear-cytoplasmic distribution of macromolecules is likely generally altered
      upon glucose deprivation due to collapse of the RanGTP gradient and
      redistribution of karyopherins between the nucleus and the cytoplasm. 

PMID- 25057024
TI  - The impact of feeding growing-finishing pigs with daily tailored diets using
      precision feeding techniques on animal performance, nutrient utilization, and
      body and carcass composition.
AB  - The impact of moving from conventional to precision feeding systems in growing
      finishing pig operations on animal performance, nutrient utilization, and body
      and carcass composition was studied. Fifteen animals per treatment for a total of
      60 pigs of 41.2 (SE = 0.5) kg of BW were used in a performance trial (84 d) with
      4 treatments: a 3-phase (3P) feeding program obtained by blending fixed
      proportions of feeds A (high nutrient density) and B (low nutrient density); a 3
      phase commercial (COM) feeding program; and 2 daily-phase feeding programs in
      which the blended proportions of feeds A and B were adjusted daily to meet the
      estimated nutritional requirements of the group (multiphase-group feeding, MPG)
      or of each pig individually (multiphase-individual feeding, MPI). Daily feed
      intake was recorded each day and pigs were weighed weekly during the trial. Body
      composition was assessed at the beginning of the trial and every 28 d by dual
      energy X-ray densitometry. Nitrogen and phosphorus excretion was estimated as the
      difference between retention and intake. Organ, carcass, and primal cut
      measurements were taken after slaughter. The COM feeding program reduced (P <
      0.05) ADFI and improved G:F rate in relation to other treatments. The MPG and MPI
      programs showed values for ADFI, ADG, G:F, final BW, and nitrogen and phosphorus
      retention that were similar to those obtained for the 3P feeding program.
      However, compared with the 3P treatment, the MPI feeding program reduced the
      standardized ileal digestible lysine intake by 27%, the estimated nitrogen
      excretion by 22%, and the estimated phosphorus excretion by 27% (P < 0.05).
      Organs, carcass, and primal cut weights did not differ among treatments. Feeding
      growing-finishing pigs with daily tailored diets using precision feeding
      techniques is an effective approach to reduce nutrient excretion without
      compromising pig performance or carcass composition. 

PMID- 25057023
TI  - Single-molecule analysis of diffusion and trapping of STIM1 and Orai1 at
      endoplasmic reticulum-plasma membrane junctions.
AB  - Following endoplasmic reticulum (ER) Ca(2+) depletion, STIM1 and Orai1 complexes
      assemble autonomously at ER-plasma membrane (PM) junctions to trigger store
      operated Ca(2+) influx. One hypothesis to explain this process is a diffusion
      trap in which activated STIM1 diffusing in the ER becomes trapped at junctions
      through interactions with the PM, and STIM1 then traps Orai1 in the PM through
      binding of its calcium release-activated calcium activation domain. We tested
      this model by analyzing STIM1 and Orai1 diffusion using single-particle tracking,
      photoactivation of protein ensembles, and Monte Carlo simulations. In resting
      cells, STIM1 diffusion is Brownian, while Orai1 is slightly subdiffusive. After
      store depletion, both proteins slow to the same speeds, consistent with complex
      formation, and are confined to a corral similar in size to ER-PM junctions. While
      the escape probability at high STIM:Orai expression ratios is <1%, it is
      significantly increased by reducing the affinity of STIM1 for Orai1 or by
      expressing the two proteins at comparable levels. Our results provide direct
      evidence that STIM-Orai complexes are trapped by their physical connections
      across the junctional gap, but also reveal that the complexes are surprisingly
      dynamic, suggesting that readily reversible binding reactions generate free STIM1
      and Orai1, which engage in constant diffusional exchange with extrajunctional
      pools.

PMID- 25057025
TI  - Prediction of digestible energy of feed ingredients for growing pigs using a
      computer-controlled simulated digestion system.
AB  - The objectives of this experiment were to evaluate in vitro DE (IVDE) of selected
      feed ingredients using a computer-controlled simulated digestion system (CCSDS)
      and predict DE of ingredients for growing pigs. Samples of 6 ingredients with a
      wide range in energy and nutrient profile were collected. The CP and GE contents
      ranged from 9.9 to 50.9% and 4,493 to 4,841 kcal/kg (DM basis), respectively. Two
      control diets were formulated to achieve different CP contents (12.5 and 20.0%).
      Three experimental diets were formulated by replacing 20% of the high-CP control
      diet with corn, wheat, or wheat bran, whereas 3 additional diets were formulated
      by replacing 20% of the low-CP control diet with soybean meal, rapeseed meal, or
      cottonseed meal. The DE was determined using barrows (n = 24; initial BW = 35.9
      +/- 1.9 kg) in 2 periods with 6 observations per diet treatment and ranged from
      2,769 to 4,368 kcal/kg. The equation for the DE content (kcal/kg of DM) using
      chemical components as independent variables was DE = 4,186 + 0.06 * CP + 79.33 *
      ether extract - 14.57 * NDF - 47.99 * ADF, with R(2) = 0.995, residual SD (RSD) =
      89.5 kcal/kg, CV = 2.4%, and P = 0.10 (chemical component values; %). The IVDE
      ranged from 2,289 to 3,724 kcal/kg and was highly related to the determined DE
      content of the ingredients (R(2) = 0.91, RSD = 193 kcal/kg, and CV = 5.2%). The
      relationship between IVDE:GE and DE:GE was very high (R(2) = 0.93, RSD = 3.8%,
      and CV = 4.7%). The average values of CV for IVDE (0.75%) and IVDE:GE (0.73%)
      were less than that for determined DE (2.58%) and DE:GE (2.54%), respectively. In
      conclusion, the IVDE content determined, using a CCSDS with relatively high
      accuracy and acceptable repeatability, might be used to predict DE of feed
      ingredients for growing pigs.

PMID- 25057026
TI  - Use of ultrasound scanning and body condition score to evaluate composition
      traits in mature beef cows.
AB  - The experiment was designed to validate the use of ultrasound to evaluate body
      composition in mature beef cows. Both precision and accuracy of measurement were
      assessed. Cull cows (n = 87) selected for highly variable fatness were used. Two
      experienced ultrasound technicians scanned and assigned BCS to each cow on 2
      consecutive days. Ultrasound traits were backfat thickness (UBFT), LM area
      (ULMA), body wall thickness (UBWT), rump fat depth (URFD), rump muscle depth
      (URMD), and intramuscular fat (UIMF; %). Cows were then harvested. Carcass traits
      were HCW, backfat thickness (CBFT), LM area (CLMA), body wall thickness (CBWT),
      and marbling score (CMS). Correlations between consecutive live measurements were
      greatest for subcutaneous fat (r > 0.94) and lower for BCS (r > 0.74) and URMD (r
      > 0.66). Repeatability bias differed from 0 for only 1 technician for URMD and
      UIMF (P < 0.01). Technicians differed in repeatability SE for only ULMA (P <
      0.05). Correlations between live and carcass measurements were high for backfat
      and body wall thickness (r > 0.90) and slightly less for intramuscular fat and LM
      area (r = 0.74 to 0.79). Both technicians underestimated all carcass traits with
      ultrasound, but only CBFT and CBWT prediction bias differed from 0 (P < 0.05).
      Technicians had similar prediction SE for all traits (P > 0.05). Technician
      effects generally explained <1% of the total variation in precision. After
      accounting for technician, animal effects explained 50.4% of remaining variation
      in differences between repeated BCS (P < 0.0001) but were minimal for scan
      differences. When cows with mean BCS <4 or >7 were removed, the portion of
      remaining variation between repeated measurements defined by animal effects
      increased for most traits and was significant for UBFT and URFD (P = 0.03).
      Technician effects explained trivial variation in accuracy (P > 0.24). Animal
      effects explained 87.2, 75.2, and 81.7% (P < 0.0001) of variation remaining for
      CBFT, CLMA, and CBWT prediction error, respectively, and remained large and
      highly important (P < 0.0001) when only considering cows with BCS from 4 to 7. We
      conclude that experienced ultrasound technicians can precisely and accurately
      measure traits indicative of composition in mature beef cows. However, animal
      differences define substantial variation in scan differences and, especially,
      prediction errors. Implications for technician certification, carcass pricing,
      and genetic evaluation are discussed. 

PMID- 25057027
TI  - Beta agonists in livestock feed: status, health concerns, and international
      trade.
AB  - Since the U.S. Food and Drug Administration approved ractopamine hydrochloride
      and zilpaterol hydrochloride in animal feeds, usage of those compounds has been a
      topic of worldwide debate. Ractopamine and zilpaterol are beta-adrenergic
      agonists used as veterinary drugs to increase weight gain in certain animals
      raised for food. The Joint FAO/WHO Expert Committee on Food Additives (JECFA)
      established maximum residue limits for ractopamine, which were adopted by the
      Codex Alimentarius Commission (Codex). No maximum residue limits for zilpaterol
      have been adopted by JECFA, and new reports of animal mobility issues confront
      the use of this feed additive. However, many countries disagree with the Codex
      standards and are restricting or banning meat products containing beta agonists.
      The bans by major importers of U.S. meat products have prompted some to advocate
      that the United States use the World Trade Organization dispute settlement body.
      This paper looks at the developments to provide a fuller accounting of what the
      issues may mean to U.S. firms selling meat products containing residues of beta
      agonists.

PMID- 25057028
TI  - Nutrient digestibility and growth performance of pigs fed diets with different
      levels of canola meal from Brassica napus black and Brassica juncea yellow.
AB  - Nutrient digestibility and the effect of high dietary inclusion of canola meals
      from Brassica napus black (BNB) and Brassica juncea yellow (BJY) on growing and
      weaned pigs performance were determined. In Exp.1, 6 ileal cannulated barrows
      (initial BW = 20.7 +/- 1.5 kg) were used to determine the apparent ileal
      digestibility (AID) and standardized ileal digestibility (SID) of AA in BNB and
      BJY. Pigs were allotted to diets containing either BNB or BJY as the sole source
      of protein in a crossover design to give 6 replicates per diet. The SID of all AA
      in BNB and BJY were similar. In Exp. 2, 168 weaned pigs (initial BW = 7.61 +/-
      0.76 kg) were assigned in a randomized complete block design to 7 diets (n = 24)
      consisting of a wheat-soybean meal-based control diet and 6 diets containing 5,
      10 or 15% of canola meal derived from either BNB or BJY to determine the effect
      of different dietary inclusion on growth performance over a 28-d period
      postweaning. Diets were formulated to contain similar NE and SID of Lys. There
      were no differences in growth performance among treatments. In Exp. 3, 162 weaned
      pigs (initial BW = 7.26 +/- 0.70 kg) were used to determine the effect of high
      BNB and BJY inclusion level without or with multicarbohydrase supplementation on
      growth performance and apparent total tract digestibility (ATTD) of CP, DM, and
      GE. A wheat-soybean meal-based control diet and 8 diets containing 20 and 25% of
      either BNB or BJY without or with added multi-carbohydrase were formulated (n =
      18) to contain comparable NE and similar SID of Lys contents. Feeding the diets
      containing 25% of BNB or BJY supported similar growth performance as those
      containing 20%. The multi-carbohydrase had no effect on growth performance but
      improved (P < 0.05) the ATTD of DM, CP, and GE compared with those fed
      nonsupplemented diets irrespective of canola meal type. Diets containing 25%
      canola meal had lower (P < 0.05) ATTD of DM, CP, and GE regardless of canola meal
      type compared with the 20% canola meal diets. There was an interaction (P < 0.05)
      between canola meal type and inclusion level on ATTD of DM in which ATTD of DM
      decreased with increasing inclusion of both canola meal types. Results of the
      current study indicate that both BNB and BJY can be included up to 25% in weaned
      pig diets without compromising performance as long as the diets are formulated on
      an NE and SID of Lys basis. Also, enzyme addition improved the ATTD of CP, DM,
      and GE in weaned pigs in both BNB and BJY diets. 

PMID- 25057029
TI  - Effects of immunological castration (Improvest) on further processed belly
      characteristics and commercial bacon slicing yields of finishing pigs.
AB  - Objectives were to compare fresh belly characteristics, further processed belly
      characteristics, and commercial bacon slicing yields of immunologically castrated
      (IC) barrows, IC barrows fed ractopamine hydrochloride (IC+RAC), physically
      castrated (PC) barrows, intact males, and gilts. One hundred eighty-eight bellies
      from pigs housed in single sex pens (n = 48) slaughtered at 130 kg ending live
      weight were evaluated for flop distance, length, width, thickness, and fatty acid
      composition. Bellies were injected, thermally processed, and sliced according to
      standard protocols at a USDA federally inspected facility. Complete slices were
      sorted by trained plant personnel. Then, sliced bellies were individually
      packaged to maintain anatomical orientation. The effects of treatments were
      analyzed as a generalized linear mixed model with pen of pigs serving as the
      experimental unit for all comparisons. Belly thickness was not different (P >=
      0.11) in bellies from IC barrows (3.74 cm) compared with bellies from IC+RAC
      (3.60 cm), PC barrows (3.94 cm), or gilts (3.64 cm); however, bellies were 0.42
      cm thicker (P < 0.01) in IC barrows compared with intact males. Iodine value was
      not different (P >= 0.06) in bellies from IC barrows (68.26) compared with
      bellies from IC+RAC (69.78), PC barrows (67.55), or gilts (69.45); however,
      iodine value was 2.32 units less (P < 0.01) in IC barrows compared with intact
      males. Green weight was not different (P >= 0.09) in bellies from IC barrows
      (4.88 kg) compared with bellies from IC+RAC (5.11 kg), PC barrows (5.10 kg), or
      gilts (4.79 kg); however, green weight was 0.56 kg greater (P < 0.0001) in IC
      barrows compared with intact males. Pump uptake and cooked yield was not
      different (P >= 0.15) among treatment groups. Slicing yield (as a percentage of
      green weight) was decreased (P <= 0.01) in bellies from IC barrows (93.61%)
      compared with bellies from PC barrows (98.42%) or gilts (98.19%); however,
      slicing yield was not different (P >= 0.11) among bellies from IC barrows,
      IC+RAC, or intact males. Overall, fresh belly characteristics of IC barrows were
      analogous to PC barrows and gilts, but commercial slicing yields of bacon
      manufactured from IC barrows were less than both PC barrows and gilts. 

PMID- 25057030
TI  - Determination of additivity of apparent and standardized ileal digestibility of
      amino acids in diets containing multiple protein sources fed to growing pigs.
AB  - An experiment was conducted in growing pigs to investigate the additivity of
      apparent ileal digestibility (AID) or standardized ileal digestibility (SID) of
      CP and AA in mixed diets containing multiple protein sources. Using the
      determined AID or SID for CP and AA in corn, soybean meal (SBM), corn distillers'
      dried grains with solubles (DDGS), or canola meal (CM), the AID or SID for 4
      mixed diets based on corn-SBM, corn-SBM-DDGS, corn-SBM-CM, or corn-SBM-DDGS-CM
      were predicted and compared with determined AID or SID, respectively. Eighteen
      growing pigs (initial BW = 61.3 +/- 5.5 kg) were surgically fitted with T
      cannulas and assigned to a duplicated 9 * 4 incomplete Latin square design with 9
      diets and 4 periods. The 9 experimental diets consisted of a nitrogen-free diet
      (NFD) to estimate basal ileal endogenous loss (BEL) of AA, 4 semipurified diets
      to determine the AID and SID of CP and AA in the 4 ingredients, and 4 mixed diets
      to test the additivity of AID and SID. Chromic oxide was added as an indigestible
      marker. Pigs were fed 1 of the 9 diets during each 7-d period, and ileal digesta
      were collected on d 6 and 7, from 0800 to 1800 h. The analyzed AA levels for the
      mixed diets were close to the calculated values based on the AA composition of
      each ingredient. The results revealed that the predicted SID were consistent with
      determined values, except for Leu, Thr, Asp, Cys, Pro, and Ser in the corn-SBM
      diet and Met and Cys in the corn-SBM-DDGS diet. The determined AID for total AA
      and Arg, His, Trp, Gly, and Pro in the corn-SBM diet were greater (P < 0.05) than
      predicted. For the corn-SBM-DDGS diet, the determined AID were greater (P < 0.05)
      than predicted AID for CP, total AA, and all AA except for Arg, Leu, and Pro. In
      the corn-SBM-CM diet, the determined AID were greater (P < 0.05) than predicted
      AID for Arg, Cys, and Gly. When compared with determined values, predicted AID in
      the corn-SBM-DDGS-CM diet were lower (P < 0.05) for total AA and Arg, Met, Cys,
      and Pro. In conclusion, the results substantiate the notion that SID of AA are
      more accurate than AID for predicting ileal digestibility of AA in mixed diets
      containing multiple protein sources. In addition, the lack of additivity of AID
      in mixed diets could be attributed to the intrinsic characteristics of the feed
      ingredient, especially its AA content. 

PMID- 25057031
TI  - Duodenal supply of glutamate and casein both improve intestinal starch digestion
      in cattle but by apparently different mechanisms.
AB  - Greater postruminal flows of protein increase small intestinal starch digestion
      in cattle. Our objective was to determine if small intestinal starch digestion is
      increased by duodenal supplementation of AA. We fed 5 duodenally and ileally
      cannulated steers a low-starch soybean hull-based diet in 5 * 5 Latin square
      designs and provided continuous duodenal infusion of raw cornstarch in
      combination with AA or casein and measured small intestinal starch digestion. In
      Exp. 1 treatments were continuous duodenal infusion of 1) no supplement
      (control), 2) casein (400 g/d), 3) crystalline AA similar in amount and AA
      composition to the casein (CASAA), 4) crystalline nonessential AA similar to
      those provided by casein, or 5) crystalline essential AA similar to those
      provided by casein. In Exp. 2 treatments were continuous duodenal infusion of 1)
      no supplement (control), 2) casein (400 g/d), 3) Glu (133 g/d), 4) Phe and Trp
      plus Met (30.4, 6.5, and 17.5 g/d, respectively; PTM), or 5) a combination of Glu
      and PTM. Duodenal infusion of casein increased (P <= 0.05) small intestinal
      starch digestion. When CASAA was infused, small intestinal starch digestion was
      similar (P = 0.30) to casein infusion. Infusion of only nonessential AA tended to
      increase (P = 0.14) small intestinal starch digestion relative to the control,
      but infusion of essential AA alone did not affect (P = 0.84) small intestinal
      starch digestion. In addition, infusion of casein or CASAA increased ileal flows
      of ethanol-soluble starch (small-chain alpha-glycosides), but nonessential AA
      alone were not different than the control. Duodenal infusion of Glu increased (P
      <= 0.05) small intestinal starch digestion, whereas PTM did not. Neither Glu nor
      PTM increased ileal flow of ethanol-soluble starch, but Glu and PTM provided
      together tended (P = 0.07) to increase ileal flows of small chain alpha
      glycosides. Our data suggest that Glu alone can increase small intestinal starch
      digestion in cattle similar to casein, but increases in small intestinal starch
      digestion in response to Glu are not associated with an increase in ileal flows
      of small chain alpha-glycosides. 

PMID- 25057032
TI  - Feeding a diet containing resistant potato starch influences gastrointestinal
      tract traits and growth performance of weaned pigs.
AB  - The aim was to evaluate the effects of feeding resistant potato starch (RPS) as a
      natural source of resistant starch to weaned pigs for 28 d immediately after
      weaning. Sixty piglets (Yorkshire-Landrace * Duroc) weaned at 21 +/- 2 d (1:1
      male:female) with an initial BW of 7.2 +/- 0.78 kg were assigned in a completely
      randomized design to 1 of 5 dietary treatments to give 6 observations per
      treatment and 2 pigs per pen. Dietary treatments consisted of a negative control
      corn-soybean meal-wheat-wheat middlings-based diet (NC; no antimicrobial agents
      added) or the NC supplemented with RPS either as powder or in capsules and each
      included at 0.5 or 1.0% as a top-dressing on each day. Diets were formulated to
      meet 1998 NRC specifications. Pigs were offered the experimental diets on an ad
      libitum basis for 28 d and water was available at all times. The ADG, ADFI, and
      G:F were determined weekly. Fecal score was determined daily for 14 d after
      weaning. At the conclusion of study, 1 pig from each pen was randomly selected
      and euthanized (n = 6 per treatment) to determine visceral organ weight, digesta
      pH, VFA, and ammonia N (NH3-N) concentrations. Resistant potato starch
      supplementation improved (P < 0.001) fecal score, and pigs offered 1.0% RPS had
      more solid feces (P < 0.05) than those offered 0.5% RPS during the first 14 d
      after weaning, independent of the form of RPS. Resistant potato starch
      supplementation decreased (P < 0.05) ileal and cecal digesta pH regardless of the
      levels of RPS or mode of delivery. The total VFA concentrations in cecal digesta
      were greater (P < 0.05) but the molar proportion of branched-chain fatty acids
      were lower (P < 0.05) for pigs fed the RPS-containing diets compared with those
      fed the NC, irrespective of the RPS levels or the form of RPS. However, there
      were no differences (P > 0.10) in visceral organ weights, growth performance, and
      digestibilities of DM, CP, Ca, and P among treatments. The results of this
      experiment indicate that supplementing a weaner pig diet with at least 0.5% RPS
      independent of mode of delivery has the potential to enhance outcomes
      characteristic of a functional gut in weaned pigs without adverse effects on
      growth. 

PMID- 25057033
TI  - Small intestinal growth measures are correlated with feed efficiency in market
      weight cattle, despite minimal effects of maternal nutrition during early to
      midgestation.
AB  - We hypothesized that gestational nutrition would affect calf feed efficiency and
      small intestinal biology, which would be correlated with feed efficiency.
      Multiparous beef cows (n = 36) were individually fed 1 of 3 diets from d 45 to
      185 of gestation: native grass hay and supplement to meet NRC recommendations
      (control [CON]), 70% of CON NEm (nutrient restricted [NR]), or a NR diet with a
      RUP supplement (NR+RUP) to provide similar essential AA as CON. After d 185 of
      gestation, cows were managed as a single group, and calf individual feed intake
      was measured with the GrowSafe System during finishing. At slaughter, the small
      intestine was dissected and sampled. Data were analyzed with calf sex as a block.
      There was no effect (P >= 0.33) of maternal treatment on residual feed intake,
      G:F, DMI, ADG, or final BW. Small intestinal mass did not differ (P >= 0.38)
      among treatments, although calf small intestinal length tended (P = 0.07) to be
      greater for NR than NR+RUP. There were no differences (P >= 0.20) in calf small
      intestinal density or jejunal cellularity, proliferation, or vascularity among
      treatments. Jejunal soluble guanylate cyclase mRNA was greater (P < 0.03) for
      NR+RUP than CON and NR. Residual feed intake was positively correlated (P <=
      0.09) with small intestinal mass and relative mass and jejunal RNA content but
      was negatively correlated (P <= 0.09) with jejunal mucosal density and DNA
      concentration. Gain:feed was positively correlated (P <= 0.09) with jejunal
      mucosal density, DNA, protein, and total cells and was negatively correlated (P
      <= 0.05) with small intestinal relative mass, jejunal RNA, and RNA:DNA. Dry
      matter intake was positively correlated (P <= 0.09) with small intestinal mass,
      relative mass, length, and density as well as jejunal DNA and protein content,
      total cells, total vascularity, and kinase insert domain receptor and endothelial
      nitric oxide synthase 3 mRNA and was negatively correlated (P = 0.02) with
      relative small intestinal length. In this study, calf performance and efficiency
      during finishing as well as most measures of small intestinal growth were not
      affected by maternal nutrient restriction during early and midgestation. Results
      indicate that offspring small intestinal gene expression may be affected by
      gestational nutrition even when apparent tissue growth is unchanged. Furthermore,
      small intestinal size and growth may explain some variation in efficiency of
      nutrient utilization in feedlot cattle. 

PMID- 25057034
TI  - Apparent total tract digestibility of dietary calcium and phosphorus and their
      efficiency in bone mineral retention are affected by body mineral status in
      growing pigs.
AB  - Improving dietary P utilization without modifying pig performance is crucial for
      production sustainability. A feeding program comprising three 28-d phases (20 to
      40, 40 to 70, and 70 to 100 kg) was used to feed 72 pigs with an initial BW of 20
      kg. The ability of the pigs to modify the digestive and metabolic utilization of
      P when fed either a control (CON) diet or a low-P (LOW) diet providing 40% less
      digestible P with a constant Ca:digestible P was studied using different
      sequences of dietary P and Ca restriction (i.e., depletion [LOW]) and recovery
      (i.e., repletion [CON]), namely CON-CON-CON, CON-CON-LOW, CON-LOW-LOW, LOW-CON
      CON, LOW-LOW-CON, and LOW-LOW-LOW. Bone mineral content (BMC) was measured in the
      lumbar region (L2-L4) by dual-energy X-ray absorptiometry at the beginning and
      end of each feeding phase. Total feces and urine were collected during phases 2
      and 3. At the end of phase 1, BMC was lower in the LOW pigs than in the C pigs
      (29%; P < 0.001). During phase 2, the BMC gain was greater in the LOW-CON pigs
      than in the CON-CON pigs (16%; P < 0.001). During phase 3, the LOW-LOW-CON pigs
      absorbed 26% more Ca (P < 0.001) and retained 56% more BMC (P < 0.001) than the
      CON-CON-CON pigs did. Digestive and metabolic adaptations allowed the LOW-LOW-CON
      and LOW-CON-CON pigs to reach BMC similar to that of the CON-CON-CON pigs. These
      metabolic adaptations are promising, but practical applications of these results
      requires a better understanding of the underlying mechanisms to fine-tune the
      degree of depletion, pig age, and the duration of P and Ca depletion and
      repletion periods. 

PMID- 25057035
TI  - The requirement of GnRH at the beginning of the five-day CO-Synch + controlled
      internal drug release protocol in beef heifers.
AB  - The objective of this study was to determine if the omission of GnRH at
      controlled internal drug release device (CIDR) insertion would impact pregnancy
      rates to timed AI (TAI) in beef heifers enrolled in a 5-d CO-Synch + CIDR
      protocol that used 1 PGF2alpha dose given at CIDR removal. Yearling beef heifers
      in Ohio in 2 consecutive breeding seasons (2011, n = 151, and 2012, n = 143;
      Angus * Simmental), Utah (2012, n = 265; Angus * Hereford), Idaho (2012, n = 127;
      Charolais), and Wyoming (2012, n = 137; Angus) were enrolled in the 5-d CO-Synch
      + CIDR protocol. At CIDR insertion (d -5), heifers were randomly assigned either
      to receive 100 MUg GnRH (GnRH+; n = 408) or not to receive GnRH (GnRH-; n = 415).
      At CIDR removal (d 0 of the experiment), 25 mg PGF2alpha was administered to all
      heifers. All heifers were inseminated by TAI and given 100 MUg GnRH 72 h after
      PGF2alpha (d 3). In heifers at the Ohio locations (n = 294), presence of a corpus
      luteum (CL) at CIDR insertion (d -5) was determined via assessment of
      progesterone concentrations (2011) and ovarian ultrasonography (2012).
      Subsequently, in both years, ovarian ultrasound was conducted on d 0 to determine
      the presence of a new CL. In this same subgroup of heifers, blood samples for
      progesterone analysis were collected on d 3 to assess luteal regression.
      Pregnancy diagnosis was performed between 32 and 38 d after TAI. At CIDR
      withdrawal, presence of a new CL was greater (P < 0.05) in the GnRH+ (55.8%,
      82/147) than GnRH- (26.5%, 39/147) treatment. Incidence of failed luteal
      regression did not differ between the GnRH+ (3.4%) and GnRH- (0.7%) treatments.
      Pregnancy rate to TAI did not differ between the GnRH+ (50.5%) and GnRH- (54.9%)
      treatments. In conclusion, although the incidence of a new CL at CIDR removal was
      increased in the GnRH+ treatment, omission of the initial GnRH treatment in the 5
      d CO-Synch + CIDR protocol did not influence TAI pregnancy rate in yearling beef
      heifers. In addition, a single dose of PGF2alpha at CIDR removal was effective at
      inducing luteolysis in yearling beef heifers enrolled in the 5-d CO-Synch + CIDR
      protocol, regardless of whether or not the initial GnRH treatment was given. 

PMID- 25057036
TI  - Mortality and causes of death among incident cases of systemic lupus
      erythematosus in Finland 2000-2008.
AB  - The objectives of the study were to investigate mortality and causes of death in
      patients with recent-onset systemic lupus erythematosus (SLE) in Finland. Data
      for patients with SLE for the study were collected (2000-2007) from the
      nationwide register on decisions of special reimbursements for drugs, maintained
      by the Social Insurance Institution (SII) in Finland. Data on deaths of the
      patients were obtained from the official death certificate statistics of
      Statistics Finland until the end of 2008. Of the 566 incident SLE patients,
      median follow-up time was 5.4 (IQR 3.3, 7.1) years, and 30 patients (23 females,
      seven males) died in the years 2000 through 2008. Mean age at death was 67.8 +/-
      17.2 years for females and 62.3 +/- 15.2 years for males. The 5-year survival
      rates were 94.8% (95%CI 92.0-96.6%) and 88.2% (95%CI 76.5-94.3%), respectively.
      The age- and sex-adjusted standardized mortality ratio was 1.48 (95%CI 1.01
      2.12). Primary causes of death were cardiovascular diseases, malignancy and SLE
      itself. In conclusion, survival of the patients with SLE was inferior to that of
      the general population. Cardiovascular diseases were responsible for 37% of
      deaths.

PMID- 25057037
TI  - Elevated C-reactive protein and self-reported disease activity in systemic lupus
      erythematosus.
AB  - C-reactive protein (CRP), a biomarker of inflammation, has been associated with
      increased disease activity in rheumatoid arthritis. However, the association in
      systemic lupus erythematosus (SLE) remains unclear. We examined the association
      of CRP with self-reported disease activity in the Carolina Lupus Study and
      described differences by sociodemographic characteristics. The study included
      baseline and three-year follow-up data on 107 African-American and 69 Caucasian
      SLE patients enrolled at a median 13 months since diagnosis. Models estimated
      prevalence differences in the association of baseline CRP with self-reported
      flares, adjusting for age, sex, race and education. Active disease or flare was
      reported by 59% at baseline and 58% at follow-up. Higher CRP (>10 ug/ml vs. <3
      ug/ml) was associated with a 17% (95% confidence interval (CI): -20, 53%) higher
      prevalence of flare at baseline and a 26% (95% CI: -9, 62%) higher prevalence of
      flare at follow-up. These CRP-flare associations were notably stronger in
      patients with lower education at baseline and in African-Americans at follow-up.
      These findings suggest that CRP may be a useful marker in studies of SLE health
      disparities.

PMID- 25057038
TI  - Identification of patients with systemic lupus erythematosus in administrative
      healthcare databases.
AB  - OBJECTIVE: Our aim was to validate and compare decision rules for the
      identification of patients with systemic lupus erythematosus (SLE) in
      administrative healthcare databases. METHODS: A retrospective cohort study was
      performed using administrative health care data from a population of 1 million
      people with access to universal healthcare. Information was available on hospital
      discharges and physician billings over a 10-year period. Each SLE case was
      matched 4:1 by age and gender to randomly selected controls. Seven case
      definitions were applied to identify SLE cases and their performance compared
      with the diagnosis by a rheumatologist. RESULTS: We identified 373 SLE cases and
      1492 non-SLE controls, all of whom had been reviewed by a rheumatologist. The
      overall accuracy of the case definitions for SLE cases varied between 88.2-95.6%
      with a kappa statistic between 0.53-0.86. The sensitivity varied from 41.0-86.6%
      and the specificity between 92.4-99.9%. In a total reference population of 1
      million the mean estimated annual incidence of SLE was between 29-255 and the
      mean estimated annual prevalence was between 172-920. CONCLUSION: The accuracy of
      case definitions for the identification of SLE patients in administrative
      healthcare databases is variable and this should be considered when comparing
      results across studies. This variability may also be used to advantage in
      different study designs depending on the relative importance of sensitivity and
      specificity for identifying the population of interest to the research question.

PMID- 25057039
TI  - APRIL levels strongly correlate with IL-17 in systemic lupus erythematosus.
AB  - INTRODUCTION: Activated self-reactive B cells play an important part in systemic
      lupus erythematosus (SLE). A proliferation-inducing ligand (APRIL) and B cell
      activating factor (BAFF) are B-cell specific stimulators, but activate B cells
      through different receptors. We investigated the reciprocal association between
      serum APRIL (s-APRIL), serum BAFF (s-BAFF) and immunological and clinical
      findings in SLE patients. METHODS: A cross-sectional case-control study was
      performed in 100 SLE patients (87% female, age 49 years, disease duration 12
      years). APRIL and BAFF levels were measured by sandwich ELISA, compared with
      healthy controls and correlated with autoantibody, cytokine (IL-6 and IL-17) and
      clinical findings through nonparametric and multivariate regression analyses.
      RESULTS: Both median s-APRIL (478 vs. 0 pg/ml, p = 0.01) and s-BAFF (1720 vs. 0.9
      pg/ml, p < 0.001) were higher in SLE patients than controls. Increased s-BAFF was
      observed in 86% of patients, while s-APRIL was increased only in 17% (p < 0.01).
      S-APRIL correlated with s-BAFF in controls (p = 0.04), but not in SLE (p = 0.8).
      Increased s-APRIL was strongly and independently associated with IL-17 activation
      (p < 0.001), while increased s-BAFF levels were associated with anti-nucleosome
      antibody presence (p = 0.001). Disease activity and organ damage were associated
      with s-BAFF but not s-APRIL. CONCLUSIONS: While both s-BAFF and s-APRIL levels
      are elevated in SLE patients, they reflect different immunologic and clinical
      pathways. The strong association between s-APRIL and IL-17 activation supports a
      role for Th17 helper cells in B cell activation in SLE.

PMID- 25057040
TI  - Increased Incidence of juvenile onset systemic lupus erythematosus in children
      with atopic dermatitis.
AB  - Herein, we investigated the risk of juvenile-onset systemic lupus erythematosus
      (JSLE) in children with atopic dermatitis (AD). From 2000 to 2007, 192,357
      children with newly diagnosed AD and 769,428 matched non-AD controls were
      identified. By the end of 2008, incidences and hazard ratios (HRs) of JSLE were
      measured. JSLE incidence in the AD cohort was 2.90-fold greater than that in the
      non-AD cohort (3.25 vs. 1.12 per 100,000 person-years), with a Cox model-measured
      adjusted HR of 2.92 (95% CI: 1.85-4.60); the risk of JSLE was greater for older
      children and girls. The AD-to-non-AD cohort HR was 6.6 (95% CI: 2.88-13.1) for
      children aged >12 years compared with 1.81 (95% CI: 0.98-3.32) for children aged
      <= 12 years. The HR of JSLE in AD children increased from 1.55 (95% CI: 0.88
      2.76) for those with <= 3 clinical visits to 66.3 (95% CI: 33.1-132.8) for those
      with >6 visits (p < 0.0001, by trend test). The risk of developing SLE in the AD
      cohort was the highest within five years after AD diagnosis (HR: 4.02; 95% CI:
      2.83-7.08). Children with AD are at a high risk of developing JSLE during their
      growth period.

PMID- 25057041
TI  - Sperm-specific post-acrosomal WW-domain binding protein (PAWP) does not cause
      Ca2+ release in mouse oocytes.
AB  - Mature mammalian oocytes undergo a prolonged series of cytoplasmic calcium
      (Ca(2+)) oscillations at fertilization that are the cause of oocyte activation.
      The Ca(2+) oscillations in mammalian oocytes are driven via inositol 1,4,5
      trisphosphate (IP3) generation. Microinjection of the sperm-derived phospholipase
      C-zeta (PLCzeta), which generates IP3, causes the same pattern of Ca(2+)
      oscillations as observed at mammalian fertilization and it is thought to be the
      physiological agent that triggers oocyte activation. However, another sperm
      specific protein, 'post-acrosomal WW-domain binding protein' (PAWP), has also
      been reported to elicit activation when injected into mammalian oocytes, and to
      produce a Ca(2+) increase in frog oocytes. Here we have investigated whether PAWP
      can induce fertilization-like Ca(2+) oscillations in mouse oocytes. Recombinant
      mouse PAWP protein was found to be unable to hydrolyse phosphatidylinositol 4,5
      bisphosphate in vitro and did not cause any detectable Ca(2+) release when
      microinjected into mouse oocytes. Microinjection with cRNA encoding either the
      untagged PAWP, or yellow fluorescent protein (YFP)-PAWP, or luciferase-PAWP
      fusion proteins all failed to trigger Ca(2+) increases in mouse oocytes. The lack
      of response in mouse oocytes was despite PAWP being robustly expressed at similar
      or higher concentrations than PLCzeta, which successfully initiated Ca(2+)
      oscillations in every parallel control experiment. These data suggest that sperm
      derived PAWP is not involved in triggering Ca(2+) oscillations at fertilization
      in mammalian oocytes.

PMID- 25057042
TI  - Inhibition of proprotein convertases abrogates processing of the middle eastern
      respiratory syndrome coronavirus spike protein in infected cells but does not
      reduce viral infectivity.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated
      with a high case-fatality rate, and the potential pandemic spread of the virus is
      a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral
      entry into host cells, which depends on activation of MERS-S by cellular
      proteases. Proteolytic activation of MERS-S during viral uptake into target cells
      has been demonstrated. However, it is unclear whether MERS-S is also cleaved
      during S protein synthesis in infected cells and whether cleavage is required for
      MERS-CoV infectivity. Here, we show that MERS-S is processed by proprotein
      convertases in MERS-S-transfected and MERS-CoV-infected cells and that several
      RXXR motifs located at the border between the surface and transmembrane subunit
      of MERS-S are required for efficient proteolysis. However, blockade of proprotein
      convertases did not impact MERS-S-dependent transduction of target cells
      expressing high amounts of the viral receptor, DPP4, and did not modulate MERS
      CoV infectivity. These results show that MERS-S is a substrate for proprotein
      convertases and demonstrate that processing by these enzymes is dispensable for S
      protein activation. Efforts to inhibit MERS-CoV infection by targeting host cell
      proteases should therefore focus on enzymes that process MERS-S during viral
      uptake into target cells. 

PMID- 25057043
TI  - The cost-effectiveness of human papillomavirus vaccine catch-up programs for
      women.

PMID- 25057044
TI  - Too late to vaccinate? The incremental benefits and cost-effectiveness of a
      delayed catch-up program using the 4-valent human papillomavirus vaccine in
      Norway.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccines are ideally administered before
      HPV exposure; therefore, catch-up programs for girls past adolescence have not
      been readily funded. We evaluated the benefits and cost-effectiveness of a
      delayed, 1-year female catch-up vaccination program in Norway. METHODS: We
      calibrated a dynamic HPV transmission model to Norwegian data and projected the
      costs and benefits associated with 8 HPV-related conditions while varying the
      upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of
      vaccine protection in women with prior vaccine-targeted HPV infections, vaccine
      cost, coverage, and natural- and vaccine-induced immunity. RESULTS: The
      incremental benefits and cost-effectiveness decreased as the upper age limit for
      catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age
      20 years remained below Norway's willingness-to-pay threshold (approximately $83
      000/quality-adjusted life year gained); extension to age 22 years was cost
      effective at a lower cost per dose ($50-$75). At high levels of vaccine
      protection in women with prior HPV exposure, vaccinating up to age 26 years was
      cost-effective. Results were stable with lower coverage. CONCLUSIONS: HPV
      vaccination catch-up programs, 5 years after routine implementation, may be
      warranted; however, even at low vaccine cost per dose, the cost-effectiveness of
      vaccinating beyond age 22 years remains uncertain.

PMID- 25057045
TI  - Intestinal microbiota, microbial translocation, and systemic inflammation in
      chronic HIV infection.
AB  - BACKGROUND: Despite effective antiretroviral therapy (ART), patients with chronic
      human immunodeficiency virus (HIV) infection have increased microbial
      translocation and systemic inflammation. Alterations in the intestinal microbiota
      may play a role in microbial translocation and inflammation. METHODS: We profiled
      the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA)
      and measured markers of microbial translocation and systemic inflammation in 21
      patients who had chronic HIV infection and were receiving suppressive ART (cases)
      and 16 HIV-uninfected controls. RESULTS: The fecal microbial community
      composition was significantly different between cases and controls. The relative
      abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales,
      Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and
      Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae
      and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was
      significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in
      cases, compared with controls. There were significant positive correlations
      between the relative abundances of Enterobacteriales and Enterobacteriaceae and
      the sCD14 level; the relative abundances of Gammaproteobacteria,
      Enterobacteriales, and Enterobacteriaceae and the interleukin 1beta (IL-1beta)
      level; the relative abundances of Enterobacteriales and Enterobacteriaceae and
      the interferon gamma level; and the relative abundances of Erysipelotrichi and
      Barnesiella and the TNF-alpha level. There were negative correlations between
      endotoxin core IgM and IL-1beta levels. CONCLUSIONS: Patients who have chronic
      HIV infection and are receiving suppressive ART display intestinal dysbiosis
      associated with increased microbial translocation and significant associations
      between specific taxa and markers of microbial translocation and systemic
      inflammation. This was an exploratory study, the findings of which need to be
      confirmed.

PMID- 25057047
TI  - Human invasive mycoses: immunogenetics on the rise.

PMID- 25057046
TI  - Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala
      infection.
AB  - BACKGROUND: Exophiala species are mostly responsible for skin infections.
      Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection,
      with 42 cases reported. About half of these cases had no known risk factors.
      Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3
      cases reported, all in patients with no known immunodeficiency. Autosomal
      recessive CARD9 deficiency has recently been reported in otherwise healthy
      patients with severe fungal diseases caused by Candida species, dermatophytes, or
      Phialophora verrucosa. METHODS: We investigated an 8-year-old girl from a
      nonconsanguineous Angolan kindred, who was born in France and developed
      disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian
      consaguineous kindred, who was living in Iran and developed disseminated E.
      spinifera disease. Both patients were otherwise healthy. RESULTS: We sequenced
      CARD9 and found both patients to be homozygous for loss-of-function mutations
      (R18W and E323del). The first patient had segmental uniparental disomy of
      chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele.
      CONCLUSIONS: These are the first 2 patients with inherited CARD9 deficiency and
      invasive Exophiala disease to be described. CARD9 deficiency should thus be
      considered in patients with unexplained invasive Exophiala species disease, even
      in the absence of other infections.

PMID- 25057048
TI  - Measuring family HRQoL spillover effects using direct health utility assessment.
AB  - BACKGROUND: Applications of cost-effectiveness analysis do not typically
      incorporate effects on caregiver quality of life despite increasing evidence that
      these effects are measurable. METHODS: Using a national sample of US adults, we
      conducted 2 cross-sectional surveys during December 2011 and January 2012. One
      version asked respondents to value their own experience as the family member of a
      person with a chronic illness (experienced sample), and the other version asked
      respondents to value hypothetical scenarios describing the experience of having a
      family member with a chronic illness (community sample). Conditions included
      Alzheimer's disease/dementia, arthritis, cancer, and depression. Using standard
      gamble questions, respondents were asked to value the spillover effects of a
      family member's illness. We used regression analysis to evaluate the disutility
      (loss in health-related quality of life) of having a family member with a chronic
      illness by condition and relationship type, controlling for the respondent's own
      conditions and sociodemographic characteristics. RESULTS: For the experienced
      sample (n = 1389), regression analyses suggested that greater spillover was
      associated with certain conditions (arthritis, depression) compared with other
      conditions (Alzheimer's disease, cancer). For the community sample (n = 1205),
      regression analyses indicated that lower spillover was associated with condition
      (cancer) but not the type of relationship with the ill family member (parent,
      child, spouse). CONCLUSIONS: The effects of illness extend beyond the individual
      patient to include effects on caregivers of patients, parents of ill children,
      spouses, and other close family and household members. Cost-effectiveness
      analyses should consider the inclusion of health-related quality of life
      spillover effects in addition to caregiving time costs incurred by family members
      of ill individuals.

PMID- 25057051
TI  - Negative Results Do Not Imply Absence of Ototoxicity with Middle Ear Application
      of Neomycin.

PMID- 25057049
TI  - A role for picomolar concentrations of pregnenolone sulfate in synaptic activity
      dependent Ca2+ signaling and CREB activation.
AB  - Fast excitatory synaptic transmission that is contingent upon N-methyl d
      aspartate receptor (NMDAR) function contributes to core information flow in the
      central nervous system and to the plasticity of neural circuits that underlie
      cognition. Hypoactivity of excitatory NMDAR-mediated neurotransmission is
      hypothesized to underlie the pathophysiology of schizophrenia, including the
      associated cognitive deficits. The neurosteroid pregnenolone (PREG) and its
      metabolites pregnenolone sulfate (PregS) and allopregnanolone in serum are
      inversely associated with cognitive improvements after oral PREG therapy, raising
      the possibility that brain neurosteroid levels may be modulated therapeutically.
      PregS is derived from PREG, the precursor of all neurosteroids, via a single
      sulfation step and is present at low nanomolar concentrations in the central
      nervous system. PregS, but not PREG, augments long-term potentiation and
      cognitive performance in animal models of learning and memory. In this report, we
      communicate the first observation that PregS, but not PREG, is a potent (EC50 ~2
      pM) enhancer of intracellular Ca(2+) that is contingent upon neuronal activity,
      NMDAR-mediated synaptic activity, and L-type Ca(2+) channel activity. Low
      picomolar PregS similarly activates cAMP response element-binding protein (CREB)
      phosphorylation (within 10 minutes), an essential memory molecule, via an
      extracellular-signal-regulated kinase/mitogen-activated protein kinase signal
      transduction pathway. Taken together, the results are consistent with a novel
      biologic role for the neurosteroid PregS that acts at picomolar concentrations to
      intensify the intracellular response to glutamatergic signaling at synaptic but
      not extrasynaptic, NMDARs by differentially augmenting CREB activation. This
      provides a genomic signal transduction mechanism by which PregS could participate
      in memory consolidation of relevance to cognitive function. 

PMID- 25057052
TI  - Response to "Negative Results Do Not Imply Absence of Ototoxicity with Middle Ear
      Application of Neomycin".

PMID- 25057054
TI  - Obituary.

PMID- 25057053
TI  - Impact of Providing a Combination Lipid Emulsion Compared With a Standard Soybean
      Oil Lipid Emulsion in Children Receiving Parenteral Nutrition: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Soybean oil lipid emulsion may compromise immune function and promote
      hepatic damage due to its composition of long-chain fatty acids, phytosterols,
      high proportion of omega-6 fatty acids, and low alpha-tocopherol levels.
      Combination lipid emulsions have been developed using medium-chain triglyceride
      oil, fish oil, and/or olive oil, which provide adequate essential fatty acids, a
      smaller concentration of omega-6 fatty acids, and lower levels of phytosterols.
      The purpose of this systematic review is to determine if combination lipid
      emulsions have a more favorable impact on bilirubin levels, triglyceride levels,
      and incidence of infection compared with soybean oil lipid emulsions in children
      receiving parenteral nutrition. METHODS: This study comprises a systematic review
      of published studies. Data were sufficient and homogeneous to conduct a meta
      analysis for total bilirubin and infection. RESULTS: Nine studies met the
      inclusion criteria. Meta-analysis showed that combination lipid emulsion
      decreased total bilirubin by a mean difference of 2.09 mg/dL (95% confidence
      interval, -4.42 to 0.24) compared with soybean oil lipid emulsion, although the
      result was not statistically significant (P = .08). Meta-analysis revealed no
      statistically significant difference in incidence of infection between the
      combination lipid emulsion and the soybean oil lipid emulsion groups (P = .846).
      None of the 4 studies that included triglyceride as an outcome detected a
      significant difference in triglyceride levels between the combination lipid
      emulsion and soybean oil lipid emulsion groups. CONCLUSION: There is inadequate
      evidence that combination lipid emulsions offer any benefit regarding bilirubin
      levels, triglyceride levels, or incidence of infection compared with soybean oil
      lipid emulsions.

PMID- 25057055
TI  - Thrombin selectively induces transcription of genes in human monocytes involved
      in inflammation and wound healing.
AB  - Thrombin is essential for blood coagulation but functions also as a mediator of
      cellular signalling. Gene expression microarray experiments in human monocytes
      revealed thrombin-induced upregulation of a limited subset of genes, which are
      almost exclusively involved in inflammation and wound healing. Among these, the
      expression of F3 gene encoding for tissue factor (TF) was enhanced indicating
      that this physiological initiator of coagulation cascade may create a feed
      forward loop to enhance blood coagulation. Activation of protease-activated
      receptor type 1 (PAR1) was shown to play a main role in promoting TF expression.
      Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required
      for expression of thrombin-regulated genes. Thrombin also increased the
      expression of TF at the protein level in monocytes as evidenced by Western blot
      and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated
      monocytes was abolished by a TF blocking antibody and therefore it is entirely
      attributable to the expression of tissue factor. This cellular activity of
      thrombin provides a new molecular link between coagulation, inflammation and
      wound healing. 

PMID- 25057056
TI  - [Inhibitory effect of trichostatin A on HepG2 cell proliferation and the
      mechanisms].
AB  - OBJECTIVE: To investigate the inhibitory effect of trichostatin A (TSA) on the
      proliferation of HepG2 cells and explore the underlying mechanism. METHODS: HepG2
      cells exposed to different concentrations of TSA for 24, 48, or 72 h were
      examined for cell growth inhibition using a cell counting kit, changes in cell
      cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI
      double staining, and cell morphology changes under inverted microscope. The
      expressions of beta-catenin, HDAC1, HDAC3, H3K9, cyclinD1 and Bax proteins in the
      exposed cells were detected by Western blotting, and the expressions of HDAC1 and
      HDAC3 mRNAs by quantitative fluorescent PCR. RESULTS: Exposure to TSA caused
      significant dose- and time-dependent inhibition of HepG2 cell proliferation
      (P<0.05) and resulted in increased cell percentage in G0/G1 and G2/M phases and
      decreased cell percentage in S phase. The apoptotic index in the control group
      was (6.22 +/- 0.25)%, which increased to (7.17 +/- 0.20)% and (18.14 +/- 0.42)%
      after exposure to 250 and 500 nmol/L TSA, respectively. Exposure to 250 and 500
      nmol/L TSA also caused cell morphology changes with numerous floating cells. The
      expressions of beta-catenin, H3K9 and Bax proteins were significantly increased
      and CyclinD1, HDAC1, and HDAC3 protein expressions decreased in TSA-treated
      cells, but the expressions of HDAC1 and HDAC3 mRNAs showed no significant
      changes. CONCLUSIONS: TSA can inhibit the proliferation of HepG2 cells and induce
      cell cycle arrest and apoptosis by inhibiting HDAC activity, promoting histone
      acetylation, and activating Wnt/beta-catenin signaling pathway.

PMID- 25057057
TI  - [Functional refinement of bushy cells in the anterior ventral cochlear nucleus
      precedes hearing onset in neonatal rats].
AB  - OBJECTIVE: To investigate the development of the electrophysiological property of
      bushy cells in the anterior ventral cochlear nucleus (AVCN) of neonatal Sprague
      Dawley (SD) rats. METHODS: The development of action potential and spontaneous
      miniature excitatory postsynaptic currents (mEPSCs) in AVCN bushy cells were
      investigated by whole-cell patch-clamp technique in SD rats during the postnatal
      days 5-21 (P5-21). The half band width of the action potential (AP), 10%-90%
      risetime and decay tau of the mEPSCs were analyzed. RESULTS: The AP of the bushy
      cells became faster with age from P5 to P21 and stopped changing around the
      period of hearing onset, as evidenced by the alteration of half band width of the
      AP. The time accuracy of mEPSCs of the bushy cells also increased with age and
      stabilized around hearing onset as shown by briefer 10%-90% rise time and decay
      tau of mEPSCs in P14/P21 than in P7. CONCLUSION: The functional refinement of the
      bushy cells in the AVCN precedes hearing onset in neonatal rats.

PMID- 25057058
TI  - [Construction of colorectal cancer cell line stably expressing mir-101 and
      identification of the target gene of mir-101].
AB  - OBJECTIVE: To construct a colorectal cancer cell line stably expressing mir-101
      and identify the target gene of mir-101. METHODS: Quantitative real-time PCR was
      used to detect mir-101 expression in colorectal cancer cell lines. The recombined
      lentiviral vector GV209-mir101 or the empty lentiviral vector GV209 was
      transfected into human colorectal cancer cells SW620. The recombinant psiCHECK-2
      Rac1 vector containing RAC1 3'UTR was constructed, and site-directed mutagenesis
      of RAC1 3'UTR was induced to construct the psiCHECK-2-Rac1-Mut vector. In HEK293A
      and SW480 cells co-transfected with mir-101 inhibitors or negative control (NC)
      and these recombined vectors, luciferase activities was examined with a dual
      luciferase reporter assay. RESULTS: SW620 cells transfected with GV209-mir101
      lentivirus exhibited higher mir-101 expression level than cells transfected with
      GV209 lentivirus. Mir-101 inhibitors significantly increased the luciferase
      activities of RAC1 3'UTR. Overexpression of mir-101 increased the expression of
      RAC1 while inhibition of mir-101 suppressed RAC1 expression. CONCLUSION: We have
      successfully constructed a SW620 cell line stably overexpressing mir-101. mir-101
      can suppress RAC1 gene expression by targeting the specific sequence of RAC1
      3'UTR.

PMID- 25057059
TI  - [Inhibitory effect of 131I-CD133mAb combined with cisplatin on liver cancer cells
      in vitro and in a tumor-bearing mouse model].
AB  - OBJECTIVE: To study the inhibitory effect of CD133 monoclonal antibody labeled
      with 131I (131I-CD133mAb) on Huh-7 human liver cancer cell line overexpressing
      CD133 antigen in vitro and in mouse models bearing the tumor cell xenograft.
      METHODS: 131I-CD133mAb was prepared by chloramines-T method and evaluated for its
      stability. Flow cytometry and immunohistochemistry were used to detect the
      expression of CD133 in Huh-7 cells and in Huh-7 cell-derived tumors,
      respectively. Huh-7 cells treated with 131I-CD133mAb plus cisplatin (DDP), 131I 
      CD133mAb, DDP, or no treatment (blank control) were examined for cell
      proliferation suppression by MTT assay with the IC50 calculated. BALB/c mice
      bearing subcutaneous Huh-7 cell xenograft in the right forelegs were treated with
      131I -CD133mAb, DDP, or both every two days for two weeks. The tumor size and
      volume were measured twice a week, and pathological examination of the tumor was
      carried out after the treatments. The tumor inhibition rate was calculated and
      tumor cell apoptosis observed with HE staining. RESULTS: The labeling ratio of
      131I-CD133mAb was 90.25% and the radiochemical purity was 97.78%. Huh-7 cells
      showed obviously higher CD133 expression than HepG2 cells. 131I-CD133mAb combined
      with DDP group resulted in a significantly higher tumor inhibition rate than
      other treatments in the tumor-bearing mice. CONCLUSION: 131I-CD133mAb can inhibit
      the growth of liver cancer cells with a high CD133 expression both in vivo and in
      vitro.

PMID- 25057060
TI  - [Screening and bioinformatics analysis of differentially expressed genes in
      hyperplastic scar].
AB  - OBJECTIVE: To screen differentially expressed genes in hyperplastic scar to
      explore the pathogenesis of hyperplastic scar and identify new therapeutic
      targets. METHODS: Three pairs of surgical specimens of hyperplastic scar and
      adjacent normal skin tissues were collected to investigate the differentially
      expressed genes in hyperplastic scar using Agilent gene oligonucletide microarray
      and clustering analysis. DAVID Bioinformatics Resources 6.7 was used for GO
      analysis and pathway analysis. RESULTS AND CONCLUSION: Distinctly different gene
      expression profiles were found between hyperplastic scar tissues and normal skin
      tissues. Compared with normal skin tissue, hyperplastic scar tissues showed 3142
      up-regulated and 2984 down-regulated genes by two folds and 28 up-regulated and
      44 down-regulated genes by 5 folds after repeating the experiment once; after
      repeating the experiment twice, 3004 genes were found up-regulated and 3038 down
      regulated by 2 folds and 25 up-regulated and 38 down-regulated by 5 folds in
      hyperplastic scars. In all the 3 specimens, 1920 genes were up-regulated and 1912
      down-regulated by 2 folds and 18 up-regulated and 29 down-regulated by 5 folds.
      The dysregulated genes in hyperplastic scar were involved in cell cycles, cell
      proliferation, immune response and cell adhesion (CDKN1C, CDKN2A, CTNNA3, COL6A3,
      and HOXB4) and in signaling pathway of focal adhesion, TGF-beta signaling
      pathway, p53 signaling pathway, cell cycle, and tumor-associated pathways
      (TGFbeta1, CDKN1C, CDKN2A, CDC14A , ITGB6, and EGF).

PMID- 25057061
TI  - [Construction of a three-dimensional visualization model of arteries supplying
      the extrahepatic bile duct based on submillimeter CT data].
AB  - OBJECTIVE: To construct a three-dimensional (3D) model of arteries supplying the
      extrahepatic bile duct with a new segmentation algorithm based on submillimeter
      CT data. METHODS: The new image segmentation algorithm based on interactive
      volume rendering was integrated into Medical Image Three-Dimensional
      Visualization System (MI-3DVS) as an intersected plug-in. The abdominal
      submillimeter CTA data of 10 patients were imported into MI-3DVS and the 3D model
      of the extrahepatic bile duct and its supplying arteries were constructed. The 3D
      model was zoomed in, zoomed out and spinned for observation and analysis of the
      arteries supplying the extrahepatic bile duct. RESULTS: The 3D models of the
      blood supply to extrahepatic bile duct allowed stereoscopic, and accurate display
      of the fourth- and fifth-level branches of the hepatic artery, the second-level
      branches of the cystic artery, the pancreatic duodenal artery arch and the
      retroportal artery. The 3D models also provided a clear vision of the biliary
      structures including the hepatobiliary tract, the left and right hepatic ducts,
      gallbladder, the liver duct, and the common bile duct. CONCLUSION: Based on the
      segmentation method of interactive volume rendering, the CT data of the
      arterioles supplying the extrahepatic bile duct can be extracted and segmented
      for 3D reconstruction to display the three-dimensional anatomical structures of
      the extrahepatic bile duct and its supplying arteries.

PMID- 25057062
TI  - [Ultrasound measurement of fetal posterior fossa at 11 to 13+6 gestational weeks
      for screening open spina bifida].
AB  - OBJECTIVE: To establish the normal reference ranges of transabdominal ultrasound
      measurements of the posterior fossa structure in fetuses at 11 to 13+6
      gestational weeks and explore their clinical value in screening open spina bifida
      (OSB). METHODS: Between January, 2013 and September, 541 randomly selected normal
      fetuses underwent nuchal translucency at the gestational age 11 to 13+6 weeks.
      The parameters of the posterior fossa were measured in mid-sagittal view of the
      fetal face and the axial view of the transverse cerebellum insonated through the
      anterior fontanel by transabdominal ultrasound to establish the normal reference
      ranges. The measurements were obtained from 3 fetuses with OSB for comparison
      with the reference ranges. RESULTS: In normal fetuses, the parameters of the
      posterior fossa measured in the two views showed no significant differences
      (P>0.05). Two high echogenic lines were observed in normal fetuses, as compared
      with one in fetuses with OSB representing the posterior border of the brain stem
      and the anterior border of the fourth ventricle. The line between the posterior
      border of the fourth ventricle and the anterior border of the cisterna magna was
      not displayed in fetuses with OSB. The anteroposterior diameters of the brain
      stem, the fourth ventricle, and cisterna magna all increased in positive
      correlation with the crown-lump length in normal fetuses. In the 3 OSB fetuses,
      the anteroposterior diameter of the brain stem exceeded the 95th percentile and
      the anteroposterior diameter of fourth ventrical-cisterner magena was below the
      5th percentile of the reference range for CRL; the brain stem to fourth ventrical
      cisterner magena anteroposterior diameter ratio was increased to above 1.
      CONCLUSION: The established normal reference ranges of the parameters of fetal
      posterior fossa may provide assistance in early OSB detection. The absence of the
      posterior border of the fourth ventricle and the anterior border of the cisterna
      magna and a brainstem to fourth ventrical-cisterner magena anteroposterior
      diameter ratio greater than 1 can be indicative of OSB at 11 to 13+6 gestational
      weeks.

PMID- 25057063
TI  - [Transfusion of necrotic cells redresses regulatory T cell and Th17 cell
      imbalance in septic mice].
AB  - OBJECTIVE: To investigate the effect of transfusion of necrotic cells on
      regulatory T (Treg) and Th17 cell balance in septic mice. METHODS: Thirty-four
      C57BL/6 mice were randomized into PBS group (n=5), sham-operated group (n=5),
      sepsis group (n=12), and necrotic cell transfusion group (n=12) and subjected to
      intraperitoneal PBS injection, sham operation by separating the cecum only, cecal
      ligation and puncture (CLP), and injection of 2 * 107 necrotic cells 5 days
      before CLP, respectively. All the mice were sacrificed 2 weeks after CLP for
      analyzing the proportion of CD4+Foxp3+Treg cells and CD4+IL17A+Th17 cells in the
      peripheral blood, spleen and thymus by flow cytometry. RESULTS: The percentage of
      Th17 cells and Treg/Th17 ratio in the spleen was significantly higher in CLP
      group than in the sham-operated group and PBS group (P<0.01). The percentage of
      Treg cells in the thymus was significantly lower in CLP group than in the sham
      operated group (P<0.01). Pre-infusion of necrotic cells redressed the abnormality
      of Treg and Th17 cell percentages and Treg/Th17 imbalance in mice following CLP
      (P<0.05). CONCLUSION: Pre-infusion of necrotic cells can reverse Treg/Th17
      imbalance in septic mice.

PMID- 25057064
TI  - [Inhibitory activities of 3-trifluoromethyl benzamide derivatives against the
      entry of H5N1 influenza viruses].
AB  - OBJECTIVE: To study the inhibitory activities of 3-trifluoromethyl benzamide
      derivatives against the entry of H5N1 influenza viruses. METHODS: The lead
      compound was structurally modified to obtain 3 compounds with inhibitory
      activities against H5N1 influenza viruses. Specs compound librany was screened
      and 4 compounds were identified to have such inhibitory activities. The
      inhibitory activities of these compounds were tested at a celluar level against
      H5N1 influenza viruses. RESULTS AND CONCLUSION: The compounds 1a, 1b, 1e and 1f
      showed signifcant inhibitory activities against the entry of A/AnHui/1/2005
      pseudovirus into the target cells with an IC50 value of 4.7 +/- 0.3 umol/L.

PMID- 25057065
TI  - [Changes of biological behavioral of E. coli K1 after ppk1 gene deletion].
AB  - OBJECTIVE: To study the changes in biological behaviors of meningitis E. coli K1
      strain E44 after deletion of polyphosphate kinase 1 (ppk1) gene and explore the
      role of ppk1 in the pathogenesis of E. coli K1-induced meningitis. METHODS: The
      wild-type strain E. coli K1 and ppk1 deletion mutant were exposed to heat at 56
      degrees celsius; for 6 min, and their survival rates were determined. The
      adhesion and invasion of the bacteria to human brain microvascular endothelial
      cells (HBMECs) were observed using electron microscopy and quantitative tests.
      HBMECs were co-incubated with wild-type strain or ppk1 deletion mutant, and the
      cytoskeleton rearrangement was observed under laser scanning confocal microscope.
      RESULTS: The survival rate of the ppk1 deletion mutant was significantly lower
      than that of the wild-type strain after heat exposure. The ppk1 deletion mutant
      also showed lowered cell adhesion and invasion abilities and weakened ability to
      induce cytoskeleton rearrangement in HBMECs. CONCLUSIONS: ppk1 gene is important
      for E.coli K1 for heat resistance, cell adhesion and invasion, and for inducing
      cytoskeletal rearrangement in HBMECs.

PMID- 25057066
TI  - [Pathological study of cerebral amyloid angiopathy in rat models of Alzheimer's
      disease].
AB  - OBJECTIVE: To examine cerebral pathologies in cerebral amyloid angiopathy in a
      rat model of Alzheimer's disease. METHODS: Rat models of Alzheimer's disease was
      established by stereotactic Abeta1-42 fiber injection in the bilateral
      hippocampus. The cognitive function of the rats was evaluated with water maze
      test. HE staining, Congo red staining and double-labeling indirect
      immunofluorescence were used to examine the dynamic distribution of Abeta fiber
      deposit in the brain. RESULTS: The model rats showed significant differences from
      the control rats in the escape latency and the times of crossing platform in
      waster maze test. HE staining revealed a decreased number and degeneration of the
      granular cells with increased glial cells in the model rats. Congo Red staining
      showed that the Abeta fiber was deposited gradually in the small vessels in the
      brain parenchyma to cause thickening, stenosis or occlusion of the small vessels.
      Immunofluorescence staining detected Abeta fiber migration from the parenchyma to
      the walls of the small arteries in the rat models. CONCLUSION: Cerebral amyloid
      angiopathy is a major pathological feature in Alzheimer's disease.

PMID- 25057067
TI  - [Analysis of hepatitis B surface antigen levels in patients with chronic
      hepatitis B in Guangzhou].
AB  - OBJECTIVE: To assess the value of quantitative analysis of hepatitis B surface
      antigen (HBsAg) levels in the diagnosis and therapeutic evaluations in patients
      with chronic hepatitis B (CHB). METHODS: According to the staging criteria
      defined by the American Association of Liver Diseases, 96 patients with CHB
      admitted in Zhujiang Hospital were classified in immune-tolerant (IT), HBeAg
      positive hepatitis (EPH), inactive carrier (IC) and HBeAg-negative hepatitis
      (ENH) phases. Serum HBsAg, HBV-DNA and ALT levels were quantified and their
      correlations were evaluated in each phase of infection. RESULTS: The mean HBsAg
      titers (measured in log10U/L) differed significantly between the phases of CHB
      (4.12 in IT, 4.02 in EPH, 2.85 in EPH, and 3.29 in ENH). The correlation
      coefficient of HBsAg with HBV-DNA was 0.6828 in IT, 0.5759 in EPH, 0.3280 in IC,
      and 0.1083 in ENH. Serum HBsAg titers were significantly higher in HBeAg-positive
      patients than in HBeAg-negative patients. No correlation was found between HBsAg
      level and ALT in each phase of CHB. CONCLUSION: The median baseline serum HBsAg
      levels vary between different phases of CHB in Guangzhou, suggesting the value of
      HBsAg in accurate classification of hepatitis B patients and evaluation of the
      therapeutic effect and outcomes of the patients.

PMID- 25057068
TI  - [Ultrasound-guided focused ultrasound ablation of intramural, submucosal and
      subserosal uterine fibroids: 12-month follow-up results].
AB  - OBJECTIVE: To evaluate the effect of ultrasound-guided focused ultrasound
      ablation (US-FUA) in the treatment of intramural, submucosal and subserosal
      uterine fibroids. METHODS: We prospectively assessed the efficacy of US-FUA for
      treatment of symptomatic uterine fibroids by determining the volume ablation
      ratio immediately after the treatment and evaluating the volume changes of the
      uterine fibroids on contrast-enhanced MRI at 6 and 12 months after the treatment.
      The symptom severity score (SSS) was examined before and at 6 and 12 months after
      the treatment. RESULTS: A total of 110 women with 145 symptomatic fibroids
      undergoing US-FUA between August 2011 and December 2012 were enrolled. The
      fibroids were located intramurally in 72 (49.7%), submucosally in 49 (33.8%) and
      subserosally in 24 (16.6%) patients, who had comparable mean volume ablation
      ratios [(93.+/- 13.1)% vs (94.9 +/- 9.3)% vs (89.6 +/- 19.3)%, P>0.05]. The
      volume of the treated fibroids was reduced by (47.3 +/- 20.8)%, (70.3 +/- 22.2)%
      and (47.8 +/- 13.6)% at 6 months after US-FUA and by (58.9 +/- 19.9)%, (82.0 +/-
      21.2)%, and (50.5 +/- 17.8)% at 12 months, respectively, demonstrating a more
      obvious volume reduction for submucosal fibroids (P<0.05). The SSS scores of the
      3 groups before treatment were 29.1 +/- 15.2, 34.8 +/- 14.5 and 26.6 +/- 23.4,
      respectively, which decreased significantly to 18.4 +/- 15.8, 15.5 +/- 10.7, and
      11.6 +/- 11.7 at 6 months (P<0.05) and to 18.9 +/- 13.2, 16.8 +/- 14.0, 11.5 +/-
      9.1 at 12 months (P<0.05). No major complications occurred in these patients
      during the 12-month follow-up. CONCLUSION: US-FUA can yield high ablation ratios
      for intramural, submucosal and subserosal fibroids and result in significant
      volume reduction and symptomatic improvement at 6 and 12 months after the
      treatment, suggesting its value as a new noninvasive option for fibroid treatment
      in patients who wish to preserve the uterus.

PMID- 25057069
TI  - [Risk factors of level Ib lymphadenopathy in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To analyze the risk factors for level Ib lymph node enlargement on CT
      in patients with nasopharyngeal carcinoma (NPC) and provide clinical evidence for
      defining the indications of prophylactic level Ib irradiation. METHODS: A total
      of 435 newly diagnosed NPC patients receiving radiotherapy in Nanfang Hospital in
      the past 2 years were enrolled in this analysis. The correlations were analyzed
      with Logistic regression between level Ib lymphadenopathy and the clinical risk
      factors including T stage, N stage, diameter of level II lymph nodes,
      submandibular gland involvement, nasal cavity involvement, oropharyngeal
      involvement, and involvement of 4 or more lymphatic drainage regions. RESULTS:
      Univariate analysis showed that level Ib lymphadenopathy were positively
      correlated with N stage (P=0.023), submandibular gland involvement (P=0.045), and
      level II lymph node diameter (P<0.001). Multivariate Logistic regression analysis
      suggested a significant correlation only between the diameter of the level II
      lymph nodes and level Ib lymphadenopathy (P=0.013). CONCLUSION: Level Ib
      lymphadenopathy is positively correlated with the size of ipsilateral level II
      lymph nodes in NPC patients.

PMID- 25057070
TI  - [Effect of statins on occurrence of infection and infection-related mortality: a
      meta-analysis].
AB  - OBJECTIVE: To systematically review whether statins can reduce the risk of
      infection and infection-related mortality. METHODS: We searched the Cochrane
      Library, MEDLINE, EMBASE, PubMed, Elsevier and CBM databases for randomized
      placebo-controlled trials of statins published by September 2013, and each trial
      enrolled at least 100 participants with follow-up for at least 4 weeks. Two
      reviewers independently assessed the quality of the included studies and
      extracted the relevant data for analysis using Stata 12.0 software. RESULTS:
      Sixteen trails involving a total of 48973 patients were included in our meta
      analysis. The results showed that statins significantly reduced the risk of
      infection (OR=0.93, 95% CI 0.89 to 0.98, P=0.004) compared to placebo but did not
      significantly lower infection-related mortality (OR=0.96, 95% CI 0.82 to 1.12,
      P=0.592). CONCLUSION: Statins can significantly reduce the risk of infection but
      does not lower infection-related mortality.

PMID- 25057071
TI  - [Correlation of platelet parameters with delayed graft function after kidney
      transplantation].
AB  - OBJECTIVE: To investigate the relationship between platelet parameters and
      delayed graft function (DGF) early after kidney transplantation. METHODS: We
      retrospectively analyzed the clinical data of 232 recipients within 2 months
      following kidney transplantation performed between January, 2009 and September,
      2013, among whom 29 experienced DGF. The laboratory data of the preoperative and
      postoperative platelets were collected from all the recipients. RESULTS: Compared
      with the preoperative levels, the platelet number (PLT) and platelet hematocrit
      (PCT) were decreased on day 1 after kidney transplantation and was the lowest on
      day 5 (P<0.05), followed by gradual increase till reaching the highest levels on
      day 15 (P<0.05) and recovery of the preoperative level in days 30-60. The average
      platelet volume (MPV), platelet volume distribution width (PDW) and large
      platelet ratio (P-LCR) were increased on day 1, highest on day 7 (P<0.05), and
      reduced to the preoperative level on day 15, but then rose again slowly. MPV and
      P-LCR in days 30 to 60 and PDW in days 45 to 60 were significantly higher than
      the preoperative levels (P<0.05). The patients with DGF showed lowered PLT than
      those without DGF since day 2, and this difference was statistically significant
      in days 7 to 10, while PCT remained comparable between the two groups; MPV, PDW,
      and P-LCR were higher in DGF group than in DGF-free group with statistically
      significant difference on days 7, 10, and 15 (P<0.05). CONCLUSION: Platelet
      function is associated with postoperative renal graft function recovery, and
      platelet parameters can provide new markers for monitoring the occurrence and
      reversion of DGF.

PMID- 25057072
TI  - [Effect of silencing Bmi-1 expression in reversing cisplatin resistance in lung
      cancer cells and its mechanism].
AB  - OBJECTIVE: To investigate the effect of silencing Bmi-1 expression in reversing
      cisplatin resistance in human lung cancer cells and explore the possible
      mechanisms. METHODS: Cisplatin-resistant A549/DDP cells with small interference
      RNA (siRNA)-mediated Bmi-1 expression silencing were examined for cisplatin
      sensitivity using MTT assay and alterations in cell cycle distribution and
      apoptosis with flow cytometry, and the changes in cell senescence was assessed
      using beta-galactosidase staining. The protein expressions of Bmi-1, P14(ARF),
      P16(INK4a), P53, P21, Rb and ubi-H2AK119 in the cells were determined with
      Western blotting. RESULTS: A549/DDP cells showed significantly higher Bmi-1
      expression than A549 cells. After siRNA-mediated Bmi-1 silencing, A549/DDP cells
      showed significantly enhanced cisplatin sensitivity with an increased IC50 from
      40.3+/-4.1 umol/L to 18.3+/-2.8 umol/L (P<0.01) and increased cell percentage in
      G0/G1 phase from (48.9+/-2.3)% to (78.7+/-7.6)% (P<0.01). Silencing Bmi-1 did not
      cause significant changes in the cell apoptosis rate but induced obvious
      senescence phenotype in A549/DDP cells with down-regulated expression of ubi
      H2AK119 and up-regulated expressions of P14(ARF), P16(INK4a), P53, P21 and Rb.
      CONCLUSION: Silencing Bmi-1 by RNA interference can induce cell senescence and
      resensitize A549/DDP cells to cisplatin possibly by regulating INK4a/ARF/Rb
      senescence pathway.

PMID- 25057073
TI  - [Lentiviral-mediated RNA interference of LXRalpha gene in donor rats with fatty
      liver enhances liver graft function after transplantation].
AB  - OBJECTIVE: To investigate whether RNA interference (RNAi) of LXRalpha gene in
      donor rats with fatty liver improves liver graft function after transplantation.
      METHODS: Fifty donor SD rats were fed a high-fat diet and 56% alcohol to induce
      macrovesicular steatosis exceeding 60% in the liver. The donor rats were injected
      via the portal veins with 7 * 107 TU LXRalpha-RNAi-LV mixture (n=25) or negative
      control-LV (NC-LV) vector (n=25) 72 h before orthotopic liver transplantation. At
      2, 24, and 72 h after the transplantation, the recipient rats were sacrificed to
      examine liver transaminases, liver graft histology, immunostaining (TUNEL), and
      protein and mRNA levels of LXRalpha. RESULTS: Lentivirus-LXRalpha RNAi inhibited
      LXRalpha gene expression at both the mRNA and protein levels in the liver graft
      and reduced the expressions of SREBP-1c and CD36 as compared with the controls,
      resulting also in reduced fatty acid accumulation in the hepatocytes. The
      recipient rats receiving RNAi-treated grafts showed more obvious reduction in
      serum ALT, AST, IL-1beta and TNF-alpha levels, and exhibited milder hepatic
      pathologies than the control rats after the transplantation. TUNEL assay
      demonstrated a significant reduction in cell apoptosis in LXRalpha-RNAi-LV
      treated liver grafts, and the rats receiving treated liver grafts had a prolonged
      mean overall survival time. CONCLUSION: LXRalpha-RNAi-LV treatment of the donor
      rats with fatty liver can significantly down-regulate LXRalpha gene expression in
      the liver graft and improve the graft function and recipient rat survival after
      liver transplantation.

PMID- 25057074
TI  - [Effects of propofol on pulmonary metastasis of intravenous injected tumor cells
      and expressions of MTA1 and Wnt1 in rats].
AB  - OBJECTIVE: To investigate the effects of different doses of propofol on pulmonary
      metastasis of intravenous injected tumor cells and expression of MTA1 and Wnt1 in
      the metastatic tumor in rats. METHODS: Forty male Fischer344 rats were randomly
      divided into 4 equal groups for intravenous administration of normal saline,
      intralipid, or propofol at the dose of 30 or 50 mg/kg pumped via the femoral
      vein. One hour after the infusion, MADB106 tumor cells (2*10) were injected
      intravenously in the rats. Pulmonary metastasis of the tumor cells was observed
      and the expression of MTA1 and Wnt1 in the metastatic tumor detected by
      immunohistochemistry 3 weeks later. RESULTS: The rats receiving saline and
      intralipid treatments showed a comparable number of pulmonary metastasis and
      similar expression levels of MTA1 and Wnt1 in the metastatic tumor (P>0.05); the
      tumor number and MTA1 and Wnt1 were significantly lower in the two propofol
      groups (P<0.01). The doses of propofol was inversely correlated with the number
      of pulmonary metastasis (r=-0.879) and expressions of MTA1 (r=-0.980) and Wnt1
      (r=-0.916) (P<0.01), and MTA1 and Wnt1 expression levels in the metastatic tumors
      were closed correlated (r=0.902, P<0.01). CONCLUSION: Propofol can dose
      dependently suppress pulmonary metastasis of intravenously injected tumor cells
      and down-regulate MTA1 and Wnt1 expressions in the metastatic tumor tissue.

PMID- 25057075
TI  - [Implantation metastasis of breast cancer in vacuum-assisted breast biopsy needle
      tract and the impact of neoadjuvant chemotherapy].
AB  - OBJECTIVE: To study the incidence of implantation metastasis of breast cancer in
      vacuum-assisted breast biopsy (VABB) needle tract in Chinese patients and
      evaluate the effect of neoadjuvant chemotherapy on needle tract metastasis
      following VABB. METHODS: The breast cancer patients with established diagnosis by
      VABB were divided into two groups to receive open surgery or neoadjuvant
      chemotherapy prior to open surgery. The incidence of needle tract metastasis,
      disease-free survival (DFS) and overall survival (OS) were compared between the
      two groups. RESULTS: A total of 214 patients were enrolled, among whom 94
      directly underwent surgeries and 120 had neoadjuvant chemotherapy before surgery.
      The two groups showed no significant differences in the incidence of needle tract
      metastasis (3.2% vs 0.8%, P=0.206), DFS (P=0.221), or OS (P=0.531). CONCLUSION:
      The incidence of needle tract metastasis is low after VABB, and neoadjuvant
      chemotherapy does not increase this risk.

PMID- 25057076
TI  - [Clinical applications of active fixation at the right ventricular outflow tract
      using a modified pacing leads model].
AB  - OBJECTIVE: To assess the feasibility and safety of using the modified active
      fixation pacing leads model to pace the right ventricular outflow tract septum.
      METHODS: A total of 136 patients undergoing artificial heart pacemaker
      implantation with active fixation pacing leads were randomized into two groups to
      receive conventional right ventricular outflow tract pacing (CRVOTP) or modified
      right ventricular outflow tract pacing (MRVOTP). The electrode lead wire core was
      modeled in a double-curved three-dimensional shape in CRVOTP group and in a J
      shaped bend in MRVOTP group before fixation at the right ventricular outflow
      tract septum. RESULTS: Right ventricular outflow tract septum pacing was achieved
      successfully in all the patients. None of patients experienced serious
      complications. No significant differences were found between the two groups in
      the number of times of electrode fixation, pacing thresholds, impedance, R wave
      height or QRS wave width during the operation, but MRVOTP was associated with a
      reduced time of X -ray exposure and operation (P<0.05) due to the convenience in
      electrode modeling and in passing the leads through the tricuspid annulus and the
      direct access to the right ventricular outflow tract septum. Postoperative follow
      up of the patients showed no incidence of active fixation pacing lead dislocation
      and comparable pacing thresholds of the ventricular electrodes, impedance, R wave
      height and QRS wave width between the two groups. CONCLUTIONS: Using the modified
      active fixation pacing leads model to pace the right ventricular outflow tract
      septum can reduce the time of X -ray exposure and operation with a low
      probability of lead damage.

PMID- 25057077
TI  - [Determination of serum carbamazepine concentration and metabonomic analysis in
      rats].
AB  - OBJECTIVE: To study the effects of carbamazepine on serum metabolic profiles in
      rats using nuclear magnetic resonance (NMR) spectroscopy. METHODS: Twenty-four
      healthy male Wistar rats were randomized into 4 groups (n=6) for daily
      intragastric administration of high-, medium- or low-dose carbamazepine or
      distilled water (control) for 7 days. Blood samples were collected from the
      abdominal aortic under anesthesia after the treatment to determine serum
      carbamazepine concentration using high-performance liquid chromatography. 1H
      nuclear magnetic resonance (1H NMR) spectra were acquired for pattern recognition
      analysis. Histopathological changes of the renal and liver tissues of the rats
      were also examined. RESULTS: Steady-state blood concentration of carbamazepine in
      high-, medium- and low-dose groups were 14.64 +/- 1.41, 8.54 +/- 1.19, and 4.56
      +/- 0.64 ug/ml, respectively. Slight liver swelling was found in high-dose group,
      but none of the groups showed renal pathologies. Compared with the control group,
      the high-dose carbamazepine group showed lowered serum concentrations of 1,3
      diaminopropane, deoxycorticosterone, 7-dehydrocholesterol, betaine, beta-alanine,
      L-cystathionine, 4-methyl-2-oxovaleric acid, and creatine with increased levels
      of saccharides, lactate, succinic acid, acetyl phosphate, and adipic acid.
      Principal component analysis revealed significant differences of the metabolites
      between carbamazepine-treated groups and the control group. The metabolic
      profiles showed no differences in the kinds of metabolites although the
      concentrations of the metabolites varied between the carbamazepine groups.
      CONCLUSIONS: Carbamazepine significantly affects metabolism in normal rats. This
      finding provides evidence for clinical drug monitoring and drug safety of
      carbamazepine. NMR technique has important values for pharmacodynamic and
      toxicological evaluation of drugs.

PMID- 25057078
TI  - [Immunoprotection by Sap2 and dendritic cells against systemic Candida albicans
      infection in mice].
AB  - OBJECTIVE: To investigate the effect of combined immunization with recombinant
      Sap2 and dendritic cells (DCs) against systemic Canddida albicans infection.
      METHODS: We constructed a prokaryotic expression vector carrying Sap2 of Candida
      albicans to obtain Sap2 protein. Murine DCs were sensitized by pulsing with
      Candida albicans spores and rope. Five groups of mice were immunized with
      recombinant Sap2 protein and sensitized DCs, sensitized DCs, naive DCs, Sap2, or
      PBS alone for 3 times, and the effect of the immunization against systemic
      Candida albicans infection were assessed by observing the survival of the mice,
      detecting the percentages of CD4+ and CD8+ cells, CFU in the kidney homogenate,
      and examining renal pathologies. RESULTS: Immunization with Sap2 and sensitized
      DCs and with DCs or Sap2 alone all prolonged the mouse survival and produced
      obvious effect in renal protection and immune enhancement, but such effects were
      more obvious with the combined immunization. CONCLUSION: Combined immunization
      with Sap2 protein and DCs offers strong immunoprotection against systemic Candida
      albicans infection in mice, which provides experimental evidence for the
      development of new combined vaccines for immunoprotection.

PMID- 25057079
TI  - [Amentoflavone induces apoptosis in SW480 human colorectal cancer cells via
      regulating beta-catenin and caspase-3 expressions].
AB  - OBJECTIVE: To investigate the role of beta-catenin and caspase-3 in amentoflavone
      induced apoptosis of human colorectal cancer SW480 cells. METHODS: MTT assay was
      used to detect the viability of SW480 cells exposed to amentoflavone, and flow
      cytometry was employed to assess the cell apoptosis. Western blotting was
      performed to determine the protein expressions of beta-catenin and caspase-3 in
      the exposed cells. RESULTS: Amentoflavone dose-dependently inhibited the
      viability of SW480 cells, and a high concentration of amentoflavone (150 umol/L)
      obviously induced apoptosis of the cells. Amentoflavone exposure caused
      significantly increased expression of caspase-3 and suppressed beta-catenin
      expression in the cells. CONCLUSION: Amentoflavone-induced apoptosis in SW480
      human colorectal cancer cells is associated with altered expressions of beta
      catenin and caspase-3.

PMID- 25057080
TI  - [Association of human chorionic gonadotropin level in embryo culture media with
      early embryo development].
AB  - OBJECTIVE: To investigate the association of human chorionic gonadotropin (HCG)
      level on day 3 of embryo culture with embryo development. METHODS: Spent culture
      media were collected from individually cultured embryos on day 3 of in vitro
      fertilization and embryo transfer (IVF-ET) cycles. HCG concentration in the
      culture media was measured using an ELISA kit and its association with embryo
      development was assessed. RESULTS: In the 163 samples of embryo culture media
      from 60 patients, HCG was positive in 153 sample (93.8%) with a mean level of
      0.85 +/- 0.43 mIU/ml. The concentration of hCG in the culture media increased
      gradually as the number of blastomeres increased (F=2.273, P=0.03), and decreased
      as the morphological grade of the embryo was lowered (F=3.900, P=0.02).
      CONCLUSION: ELISA is capable of detecting HCG levels in spent culture media of
      embryos on day 3 of in vitro culture. The concentration of HCG in spent culture
      media is positively correlated with the status of early embryo development and
      implantation rate and thus serves as a useful marker for embryo selection in IVF
      ET procedure.

PMID- 25057081
TI  - [Expression of Runx3 and C-myc in human colorectal cancer].
AB  - OBJECTIVE: To investigate Runx3 and C-myc expressions in colorectal cancer and
      their relationship with the clinicopathological parameters. METHODS: Real-time
      quantitative PCR was used to detect Runx3 and C-myc mRNA expressions in 38
      colorectal cancer tissues and matched adjacent tissues, and Runx3 and C-myc
      expressions was detected by Western blotting in 63 pairs of colorectal cancer and
      adjacent tissues. The results were stratified according to the
      clinicopathological characteristics to examine the relationship of Runx3 and C
      myc expressions with the clinicopathological factors in the patients. RESULTS:
      Runx3 expression was down-regulated and C-myc expression up-regulated at both
      mRNA and protein levels in colorectal cancer tissues compared with the normal
      tissues, and their protein expressions exhibited an inverse correlation (r=
      0.398, P=0.001). Runx3 and C-myc expressions differed significantly between
      tumors with different Dukes stages, depths of tumor invasion, lymph node
      statuses, or histological differentiation (P<0.05); Runx3 down-regulation and C
      myc up-regulation were more obvious in tumors in advanced Dukes stage and in
      poorly differentiated tumors. CONCLUSION: Abnormal expressions in Runx3 and C-myc
      may contribute to the occurrence and development of colorectal cancer and are
      closed correlated with the patient's clinicopathological parameters.

PMID- 25057082
TI  - [Effect of low-molecular-weight heparin combined with doxorubicin on
      hepatocellular cancer cell migration in vitro].
AB  - OBJECTIVE: To investigate the anti-cancer effect of low-molecular-weight heparin
      (LMWH) combined with doxorubicin and explore the mechanism. METHODS:
      Hepatocellular cancer HepG2 cells exposed to LMWH, doxorubicin, or both were
      evaluated for cell viability with MTT assay and for changes in their migration
      ability using wound healing assay and Transwell migration assay. The changes in
      cellular expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 mRNA and
      proteins were analyzed with quantitative real-time PCR (qRT-PCR) and Western
      blotting, and ELISA was used to determine heparanase (HPA) concentration in the
      cell culture medium. RESULTS: HepG2 cells exhibited suppressed proliferation in
      response to LMWH and doxorubicin treatments. The combined treatment caused a
      significantly higher inhibition rate of cell migration than LMWH and doxorubicin
      alone. LMWH enhanced doxorubicin-induced down-regulation of MMP-9, MMP-2 and HPA
      in the cells. CONCLUSIONS: LMWH can enhance the inhibitory effect of doxorubicin
      on the migration of HepG2 cells, the mechanism of which may involve the down
      regulation of MMP-9, MMP-2 and HPA expressions.

PMID- 25057083
TI  - [Intraoperative methylene blue and (99m)Tc-sulfur colloid isotope tracing for
      sentinel node mapping in early-stage non-small cell lung cancer].
AB  - OBJECTIVE: To compare the accuracy of intaoperative methylene blue alone and in
      combination with (99m)Tc-sulfur colloid isotopic tracing for detection of
      sentinel lymph nodes (SLNs) in early-stage non-small cell lung cancer (NSCLC).
      METHODS: Sixty-one patients with operable NSCLC who did not receive previous
      radiotherapy or chemotherapy were enrolled. Methylene blue and (99m)Tc-sulfur
      colloid were injected into the subserosal layer adjacent to the tumor, and SLNs
      were defined as those with blue staining or those containing 3 times more
      radioactivity than the surrounding tissue detected with a gamma probe. The SLN
      were removed with systematic lymph node dissection. All the removed lymph nodes
      were examined histopathologically with HE staining and immunohistochemistry.
      RESULTS: Methylene blue alone showed a low detection rate (60.0%) and sensitivity
      (58.33%) for SLNs compared with the combination of methylene blue and isotope
      tracing (96.15% and 92.86%, respectively). CONCLUSION: The combination of
      methylene blue and (99m)Tc-sulfur colloid isotopic tracing allows accurate
      detection of the SLNs in early-stage NSCLC.

PMID- 25057084
TI  - [Effect of S-1 maintenance chemotherapy following DCF regimen in patients with
      advanced gastric cancer].
AB  - OBJECTIVE: To investigate the efficacy and adverse effect of DCF regimen with
      subsequent S-1 maintenance chemotherapy in patients with advanced gastric cancer
      (AGC). METHODS: Sixty AGC patients without disease progression after 4 to 6
      cycles of DCF regimen as the first-line chemotherapy were randomized into
      maintenance group and control group (30 patients each). The patients in the
      maintenance group received maintenance chemotherapy with S-1 (40 mg/m(2), twice
      daily for 14 days; 21 days for a treatment cycle) until disease progression or
      with intolerant toxicity, and those in the control group received optimal
      supportive care. RESULTS: The response rate (CR+PR) was 33.3% in the maintenance
      group, significantly higher than that in the control group (3.33%, P<0.05), and
      the disease control rate (CR+PR+SD) also differed significantly between the two
      groups (73.3% vs 46.7%, P<0.05). The median time to progression was 7.9 months in
      the maintenance group and 6.8 months in the control group, with median overall
      survival time of 13.8 and 11.7 months, respectively (P>0.05). The most common
      adverse effect in the maintenance group included nausea, vomiting,
      leucocytopenia, and hand-foot syndrome; no death occurred in relation to the
      therapy. CONCLUSION: S-1 maintenance chemotherapy, with a tolerable toxicity
      profile, can improve the RR, DCR and median time to progression in AGC patients
      who respond to DCF regimen, but its efficacy still awaits further evaluation.

PMID- 25057085
TI  - [Effects of chronic intermittent hypoxia on glucose transporter 4 expression in
      rat skeletal muscles].
AB  - OBJECTIVE: To study the effect of chronic intermittent hypoxia-induced
      inflammatory cytokines and reoxygenation on glucose transporter 4 (GLUT-4)
      expression in rat skeletal muscles. METHODS: Twenty-four male Sprague-Dawley rats
      were randomly assigned to blank control group, chronic intermittent hypoxia (CIH)
      group, and reoxygenation group. At the end of the experiment, fasting blood
      glucose (FBG), fasting blood insulin (FINS) and serum inflammatory cytokine
      levels were measured with glucose oxidase-peroxidase, insulin radioimmunoassay
      and ELISA, respectively. Homeostasis model assessment (IRI) was used to evaluate
      insulin resistance in the rats, and GLUT-4 protein expression in the skeletal
      muscles was measured with Western blotting. RESULTS: Compared with the blank
      control group, CIH resulted in significantly increased fasting blood glucose,
      blood insulin levels and insulin resistance index (IRI) (P<0.05); fasting blood
      glucose was significantly elevated in reoxygenation group (P<0.05). Inflammatory
      cytokines levels (IL-6 and TNF-alpha) were significantly higher in CIH group than
      in the blank control and reoxygenation groups (P<0.05), and were higher in
      reoxygenation group than in the blank control group. GLUT-4 expression in the
      skeletal muscles was significantly reduced after CIH (P<0.05) but increased after
      subsequent reoxygenation (P<0.05). CONCLUSION: CIH can cause increased release of
      inflammatory cytokines to lower GLUT-4 protein expression in the skeletal
      muscles, which contributes to insulin resistance in adult rats.

PMID- 25057086
TI  - [Is axillary interventions necessary in early breast cancer?].
AB  - OBJECTIVE: Axillary interventions, represented by axillary lymph node dissection
      (ALND), has been a key component in radical surgeries for breast cancer since the
      proposal of radical mastectomy. ALND substantially affects the quality of life of
      the patients. In recent years, many studies suggested that axillary interventions
      may not be necessary for all breast cancer patients, and for early early-stage
      patients, it brings more harm than benefit. Sentinel lymph node biopsy (SLNB) has
      provided good guidance to indicate the necessity of ALND, but several studies
      revealed that not all patients with positive SLNB results benefited from ALND. In
      this review, the authors summarize the recent progress of researches of these two
      hot issues.

PMID- 25057087
TI  - [Relationship between fetal growth restriction and angiogenesis factors].
AB  - OBJECTIVE: Placenta is an important organ to maintain fetal growth, metabolism,
      maternal and fetal physiologic balance. Angiogenesis is a critical factor in
      placental development involved in fetal blood circulation and vascular changes in
      the endometrium and placenta. Angiogenesis is closely related to angiogenesis
      factors such as vascular endothelial growth factor and placenta growth factor.
      Fetal growth restriction threats the fetal health in gestation and also increases
      the long-term likeliness of several diseases. In this review, the authors
      summarize the findings in current studies of the relationship between
      angiogenesis factors and fetal growth restriction.

PMID- 25057088
TI  - [siRNA-mediated CDK6 knockdown suppresses nasopharyngeal carcinoma cell growth
      and cell cycle transition in vitro].
AB  - OBJECTIVE: To assess the effect of small interfering RNA (siRNA)-mediated
      suppression of CDK6 expression on the proliferation and cell cycles of
      nasopharyngeal carcinoma (NPC) cells in vitro. METHODS: QRT-PCR was used to
      examine the differential expression of CDK6 in 30 NPC tissues and 18 normal
      nasopharyngeal tissues. A siRNA targeting CDK6 was transfected in NPC CNE2 cells,
      and MTT assay and flow cytometry were used to analyze the changes in cell
      proliferation and cell cycle distribution. Western blotting was used to examine
      the expressions of the cell cycle-related factors. RESULTS: Compared with normal
      nasopharyngeal tissues, NPC tissues showed an increased expression of CDK6 mRNA.
      Knocking down CDK6 expression obviously inhibited tumor cell growth and cell
      cycle transition from G1 to S phase and caused reduced expressions of CDK4,
      CCND1, and E2F1 and enhanced expression of the tumor suppressor p21. CONCLUSION:
      NPC tissues overexpress CDK6. Knocking down CDK6 expression inhibits the growth
      and cell cycle transition of NPC cells in vitro by inhibiting the expressions of
      CDK4, CCND1, and E2F1 and upregulating tumor suppressor p21 expression.

PMID- 25057089
TI  - [Changes of platelet mitochondria in rats with tourniquet-induced limb ischemia-
      reperfusion injury].
AB  - OBJECTIVE: To investigate the changes of platelet mitochondria in rats with
      tourniquet-induced limb ischemia-reperfusion (IR) injury. METHODS: Thirty SD rats
      were randomized equally into 5 groups including a control group and 4 limb IR
      injury groups for blood sampling at 2, 6, 12, or 24 h following IR injury induced
      by tourniquet on the thighs for 4 h. Platelet was separated from the blood
      samples for measurement of ATP content, mitochondrial membrane potentials, plasma
      cytochrome C level, and hydroperoxides. RESULTS: Compared with the control group,
      the rats with tourniquet-induced limb IR injury showed significantly decreased
      ATP content, lowered mitochondrial membrane potential, and increased plasma
      cytochrome C and hydroperoxide levels in the platelets at 2 and 6 h following the
      injury (P<0.05 or 0.01). These alterations recovered partially but remained
      significantly different from the control levels at 12 h (P<0.05 or 0.01) until
      full recovery at 24 h. Limb IR injury did not cause significant variations of the
      platelet counts. CONCLUSION: Tourniquet-induced limb IR injury can cause
      mitochondrial damage in the platelets, which occurs mainly in the early stage (6
      h) and recovers gradually afterwards without significant impact on platelet
      counts.

PMID- 25057090
TI  - Comparison of two 22 G aspiration needles for histologic sampling during
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).
AB  - OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration is
      widely used for mediastinal and hilar lesions. Histologic specimens from this
      procedure are important for specific diagnosis and targeted therapy. Studies on
      the traditional endobronchial ultrasound-guided transbronchial needle aspiration
      needles reported yields of only 50-60% for diagnostic histologic specimens.
      Recently, a new needle has become available in Europe, USA and Asia. The
      investigators aimed to evaluate the histologic specimen retrieval yields of the
      two needles. METHODS: Patients who underwent endobronchial ultrasound-guided
      transbronchial needle aspiration with the new 22 G needle (M group, n = 94) were
      compared with a historical control group who underwent endobronchial ultrasound
      guided transbronchial needle aspiration with the traditional 22 G needle (O
      group, n = 82). The quality of needle aspirates from both groups was evaluated.
      RESULTS: There were no significant differences between the two groups in terms of
      demographics, lesion characteristics, primary disease and examiner experience.
      The M group had a significantly shorter procedure time than the O group (P =
      0.049). Of the 214 punctures by the M group, 159 (74.3%) were diagnostic, 28
      (13.1%) were non-diagnostic and 27 (12.6%) had no histologic specimen. The 235
      punctures by the O group were diagnostic in 144 (61.3%), non-diagnostic in 60
      (25.5%) and had no histologic specimen in 31 (13.2%). The yield for diagnostic
      histologic specimens of the M group was significantly higher than the O group (P
      = 0.0035). There were no major complications observed. CONCLUSIONS: The yield for
      diagnostic histologic specimens by the new 22 G endobronchial ultrasound-guided
      transbronchial needle aspiration needle was high. Further technical improvements
      of histologic sampling yields are very important when selecting targeted therapy.

PMID- 25057091
TI  - Knee reconstruction with endoprosthesis after extra-articular and intra-articular
      resection of osteosarcoma.
AB  - OBJECTIVE: Extra-articular resection is necessary to obtain a wide margin for
      primary osteosarcomas invading the knee joint, and the limb is often
      reconstructed using a prosthesis. Here, outcomes of extra-articular and intra
      articular procedures were compared. METHODS: Between 1999 and 2012, 14 patients
      with osteosarcoma underwent extra-articular excision (n = 6; ages 23-65 years;
      mean follow-up 82.8 months) or intra-articular excision (n = 8; ages 8-58 years;
      mean follow-up 96.4 months). In the extra-articular group, there was one Enneking
      Stage IIA case and five Enneking Stage IIB cases. No local recurrences were noted
      in either group. RESULTS: Patient outcomes were as follows (extra-articular cases
      vs. intra-articular cases): continuous disease-free (2 vs. 7), alive with disease
      (2 vs. 0) and death from disease (1 vs. 1). Average Musculoskeletal Tumor Society
      functional scores were 69.4% (range 63.3-83.3%) and 88.3% (range 70.0-96.7%) in
      the extra-articular and intra-articular groups, respectively, constituting a
      significant difference (P < 0.05). The 5-year oncological overall survival
      exceeded 80% in both groups. Amputation was necessary for one patient in the
      extra-articular group. The 5-year event-free prosthesis survival rates in the
      extra-articular and intra-articular groups were 33.3 and 75.0%, respectively (P <
      0.05). CONCLUSION: The extra-articular excision group developed more
      complications than the intra-articular excision group, as a result of extensive
      bone and muscle excision. The limb survival rates were similar in both groups.
      Our results suggest that extra-articular resection was a necessary and clinically
      acceptable procedure.

PMID- 25057092
TI  - Low-dose irinotecan as a second-line chemotherapy for recurrent small cell lung
      cancer.
AB  - OBJECTIVE: Irinotecan is a potent inhibitor of deoxyribonucleic acid
      topoisomerase 1 and the weekly schedule of 100-125 or 350 mg/m(2) administration
      on Day 1 every 3 weeks is recommended for recurrent small cell lung cancer.
      However, severe gastrointestinal toxic effects and myelosuppression are often
      observed in this dose setting. We conducted a retrospective study to evaluate the
      efficacy and safety of low-dose irinotecan monotherapy (60 mg/m(2) on Days 1, 8
      and 15 every 4 weeks) as second-line chemotherapy for small cell lung cancer.
      METHODS: The medical charts of small cell lung cancer patients who had received
      second-line chemotherapy at the National Cancer Center Hospital East between
      April 2003 and June 2012 were reviewed. Consecutive 57 patients who were treated
      with low dose of irinotecan (60 mg/m(2) on Days 1, 8 and 15 every 4 weeks) were
      analyzed in this study. RESULTS: Median age was 70 years (range, 51-83). Fifty
      two (91%) were male, 36 (63%) had an Eastern Cooperative Oncology Group
      performance status 0-1 and 26 (46%) were sensitive relapse. The median number of
      chemotherapy cycles was 2. The objective response rate was 32% (95% confidence
      interval: 20-45%).The median progression-free survival and the median overall
      survival were 2.9 months (95% confidence interval: 1.9-3.4 months) and 5.3 months
      (95% confidence interval: 3.6-7.6 months), respectively. The incidence of Grade
      3/4 neutropenia, diarrhea and nausea/vomiting was 21, 4 and 5%, respectively.
      CONCLUSIONS: Low-dose irinotecan monotherapy for recurrent small cell lung cancer
      might be effective with favorable toxicity. Randomized trial of 60 mg/m(2) versus
      standard dose of irinotecan is warranted.

PMID- 25057093
TI  - Clinicopathological features and outcomes of gastric cancer patients with
      pulmonary lymphangitis carcinomatosa.
AB  - OBJECTIVE: Breast, gastric and lung cancers are the most common cancers that
      cause pulmonary lymphangitis carcinomatosa. However, little is known about the
      clinical features of pulmonary lymphangitis carcinomatosa in advanced gastric
      cancer. METHODS: We retrospectively reviewed the data throughout the clinical
      courses of 33 patients with gastric cancer who developed pulmonary lymphangitis
      carcinomatosa. Pulmonary lymphangitis carcinomatosa was confirmed by both a
      pulmonologist and a diagnostic radiologist on the basis of computed tomography
      findings of interstitial patterns such as thickening or irregularity of
      interlobular septa and bronchovascular bundles. RESULTS: The median age of the 33
      patients was 55 years old (range, 25-73 years). The percentages of female
      patients, those with performance status 3 or 4, and those with respiratory
      symptoms at diagnosis were 70, 36 and 76%, respectively. The histologically
      diffuse type of gastric cancer accounted for 85% of cases. Mediastinal lymph
      node, peritoneal and bone metastases were found in 64, 61 and 39% of patients,
      respectively. Disseminated intravascular coagulation was noted in 21% of
      patients. The median survival time of the 18 chemotherapy-naive patients treated
      with chemotherapy was 5.7 months (range, 0.4-37.0 months). Two patients obtained
      symptomatic relief, and one patient treated with S-1 + cisplatin + sunitinib
      survived >3 years. CONCLUSIONS: Pulmonary lymphangitis carcinomatosa caused by
      gastric cancer has some specific clinicopathological features. While the
      prognosis of gastric cancer patients with pulmonary lymphangitis carcinomatosa is
      extremely poor, some patients may have survival benefit from chemotherapy.

PMID- 25057094
TI  - Experimental and computational investigation of Morse taper conometric system
      reliability for the definition of fixed connections between dental implants and
      prostheses.
AB  - Nowadays, dental implantology is a reliable technique for treatment of partially
      and completely edentulous patients. The achievement of stable dentition is
      ensured by implant-supported fixed dental prostheses. Morse taper conometric
      system may provide fixed retention between implants and dental prostheses. The
      aim of this study was to investigate retentive performance and mechanical
      strength of a Morse taper conometric system used as implant-supported fixed
      dental prostheses retention. Experimental and finite element investigations were
      performed. Experimental tests were achieved on a specific abutment-coping system,
      accounting for both cemented and non-cemented situations. The results from the
      experimental activities were processed to identify the mechanical behavior of the
      coping-abutment interface. Finally, the achieved information was applied to
      develop reliable finite element models of different abutment-coping systems. The
      analyses were developed accounting for different geometrical conformations of the
      abutment-coping system, such as different taper angle. The results showed that
      activation process, occurred through a suitable insertion force, could provide
      retentive performances equal to a cemented system without compromising the
      mechanical functionality of the system. These findings suggest that Morse taper
      conometrical system can provide a fixed connection between implants and dental
      prostheses if proper insertion force is applied. Activation process does not
      compromise the mechanical functionality of the system. 

PMID- 25057095
TI  - Duration of memory of dominance relationships in a group living cichlid.
AB  - Animal contests are costly and tend to escalate when rivals have similar
      competitive abilities. Individuals that remember dominance relationships with
      rivals may avoid repeated agonistic interactions and hence avoid the costs of
      repeated escalation of contests. However, it can be difficult to experimentally
      disentangle the effects of memory from those of loser effects (losers behaving
      subordinately due to prior defeats). Here, we test whether loser effects or
      individual memory mediate contest behaviour in the African cichlid, Julidochromis
      transcriptus. We find that on days 3 and 5 after initial contests, losers display
      subordinate behaviour to contest winners but not to novel contestants. However,
      this effect disappears after 7 days, at which time losers do not display
      subordinate behaviour to either rival. These results show that (1) this fish can
      recall a previously dominant contestant for up to 5 days and (2) as no
      subordinate displays were shown to the novel contestant, there are no evidences
      for loser effects in this species. Such short-term memory of past interactions
      may have broad significance in social species with repeated interactions.

PMID- 25057096
TI  - In silico comparative characterization of pharmacogenomic missense variants.
AB  - BACKGROUND: Missense pharmacogenomic (PGx) variants refer to amino acid
      substitutions that potentially affect the pharmacokinetic (PK) or pharmacodynamic
      (PD) response to drug therapies. The PGx variants, as compared to disease
      associated variants, have not been investigated as deeply. The ability to
      computationally predict future PGx variants is desirable; however, it is not
      clear what data sets should be used or what features are beneficial to this end.
      Hence we carried out a comparative characterization of PGx variants with
      annotated neutral and disease variants from UniProt, to test the predictive power
      of sequence conservation and structural information in discriminating these three
      groups. RESULTS: 126 PGx variants of high quality from PharmGKB were selected and
      two data sets were created: one set contained 416 variants with structural and
      sequence information, and, the other set contained 1,265 variants with sequence
      information only. In terms of sequence conservation, PGx variants are more
      conserved than neutral variants and much less conserved than disease variants. A
      weighted random forest was used to strike a more balanced classification for PGx
      variants. Generally structural features are helpful in discriminating PGx variant
      from the other two groups, but still classification of PGx from neutral
      polymorphisms is much less effective than between disease and neutral variants.
      CONCLUSIONS: We found that PGx variants are much more similar to neutral variants
      than to disease variants in the feature space consisting of residue conservation,
      neighboring residue conservation, number of neighbors, and protein solvent
      accessibility. Such similarity poses great difficulty in the classification of
      PGx variants and polymorphisms.

PMID- 25057098
TI  - American Association of Clinical Endocrinologists and American College of
      Endocrinology Protocol for Standardized Production of Clinical Practice
      Guidelines, Algorithms, and Checklists--2014 Update and the AACe G4G Program.
AB  - In 2010, the American Association of Clinical Endocrinologists (AACE) published
      an update to the original 2004 guidelines. This update hybridized strict evidence
      based medicine methods with subjective factors and improved the efficiency of
      clinical practice guidelines (CPG) production, clinical applicability, and
      usefulness. Current and persistent shortcomings involving suboptimal
      implementation and protracted development timelines are addressed in the current
      2014 update. The major advances include 1) formulation of an organizational
      educational strategy, represented by the AACE Council on Education, to address
      relevant teaching and decision-making tools for clinical endocrinologists, and to
      generate specific clinical questions to drive CPG, clinical algorithm (CA), and
      clinical checklist (CC) development; 2) creation and prioritization of printed
      and online CAs and CCs with a supporting evidence base; 3) focus on clinically
      relevant and question-oriented topics; 4) utilization of "cascades," where there
      can be more than 1 recommendation for 1 clinical question; and 5) incorporation
      of performance metrics to validate, optimize, and effectively update CPG, CAs,
      and CCs. Efforts continue to translate these clinical tools to electronic formats
      that can be integrated into a paperless healthcare delivery system, as well as
      applying them to diverse clinical settings by incorporating transcultural
      factors. 

PMID- 25057097
TI  - Circadian regulators of intestinal lipid absorption.
AB  - Among all the metabolites present in the plasma, lipids, mainly triacylglycerol
      and diacylglycerol, show extensive circadian rhythms. These lipids are
      transported in the plasma as part of lipoproteins. Lipoproteins are synthesized
      primarily in the liver and intestine and their production exhibits circadian
      rhythmicity. Studies have shown that various proteins involved in lipid
      absorption and lipoprotein biosynthesis show circadian expression. Further,
      intestinal epithelial cells express circadian clock genes and these genes might
      control circadian expression of different proteins involved in intestinal lipid
      absorption. Intestinal circadian clock genes are synchronized by signals
      emanating from the suprachiasmatic nuclei that constitute a master clock and from
      signals coming from other environmental factors, such as food availability.
      Disruptions in central clock, as happens due to disruptions in the sleep/wake
      cycle, affect intestinal function. Similarly, irregularities in temporal food
      intake affect intestinal function. These changes predispose individuals to
      various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and
      atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal
      triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation
      of lipid absorption. 

PMID- 25057099
TI  - AACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease.
AB  - OBJECTIVE: To review available medical therapies for patients with Cushing
      disease and to provide a roadmap for their use in clinical practice. METHODS:
      PubMed searches were performed to identify all of the available published data on
      medical management of Cushing disease. RESULTS: Medical therapy is usually not
      the first-line treatment for patients with Cushing disease but may be used to
      improve clinical manifestations of Cushing disease in patients who are not
      suitable candidates for surgery, following unsuccessful surgery or recurrence, or
      as a "bridge therapy" in those who have undergone radiotherapy. Medical therapy
      may also be used in preoperative preparation of patients with severe disease.
      Current available medical options for patients with Cushing disease include
      centrally acting agents, steroidogenesis inhibitors, and a glucocorticoid
      receptor antagonists. At present, there are no head-to-head studies comparing the
      efficacy, tolerability, and safety of different U.S. Food and Drug Administration
      (FDA)- and non-FDA-approved drugs in patients with Cushing disease. With the
      initiation of new studies and the completion of ongoing clinical trials, the
      number of FDA-approved drugs for medical treatment of Cushing disease is expected
      to increase. CONCLUSION: Medical therapy has an important adjunctive role in the
      management of patients with Cushing disease. The decision to initiate medical
      treatment depends on many factors, including patient characteristics and
      preference. Long-term studies are needed to better define the clinical efficacy,
      safety, and tolerability of medical treatment of Cushing disease, including the
      role of combination therapies.

PMID- 25057100
TI  - Editorial commentary: Treatment for multidrug-resistant tuberculosis: it's worse
      than we thought!

PMID- 25057101
TI  - Extensive drug resistance acquired during treatment of multidrug-resistant
      tuberculosis.
AB  - BACKGROUND: Increasing access to drugs for the treatment of multidrug-resistant
      (MDR) tuberculosis is crucial but could lead to increasing resistance to these
      same drugs. In 2000, the international Green Light Committee (GLC) initiative
      began to increase access while attempting to prevent acquired resistance.
      METHODS: To assess the GLC's impact, we followed adults with pulmonary MDR
      tuberculosis from the start to the end of treatment with monthly sputum cultures,
      drug susceptibility testing, and genotyping. We compared the frequency and
      predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that
      volunteered to participate, 5 countries that met GLC criteria, and 4 countries
      that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of
      those without baseline resistance to specific SLDs, 68 (8.9%) acquired
      extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired
      fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line
      injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of
      acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR
      tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3
      different SLIs. The risk increased as the number of potentially effective drugs
      decreased. Controlling for baseline drug resistance and differences between
      sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR
      tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. CONCLUSIONS:
      Treatment of MDR tuberculosis involves substantial risk of acquired resistance to
      SLDs, increasing as baseline drug resistance increases. The risk was
      significantly lower in programs documented by the GLC to meet specific standards.

PMID- 25057102
TI  - The effect of therapeutic lumbar punctures on acute mortality from cryptococcal
      meningitis.
AB  - INTRODUCTION: Cryptococcal meningitis is the most common cause of adult
      meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in
      cryptococcosis. Prior studies suggest elevated ICP is associated with mortality,
      and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However,
      the magnitude of the impact of LPs on cryptococcal-related mortality is unknown.
      METHODS: In sum, 248 individuals with human immunodeficiency virus (HIV)
      associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART
      Timing (COAT) trial in Uganda and South Africa, were observed. Individuals
      received an LP to diagnose meningitis, and subsequent therapeutic LPs were
      recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival,
      through 11 days, between individuals receiving at least 1 therapeutic LP with
      individuals not receiving therapeutic LPs. The COAT trial randomized subjects at
      7-11 days; thus, follow-up stopped at time of death, randomization, or 11 days.
      RESULTS: Seventy-five (30%) individuals had at least 1 therapeutic LP.
      Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF)
      opening pressures, higher CSF fungal burdens, and were more likely to have
      altered mental status at baseline than those with no therapeutic LPs. Thirty-one
      deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths
      (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of
      mortality was 0.31 (95% confidence interval: .12-.82). The association was
      observed regardless of opening pressure at baseline. CONCLUSIONS: Therapeutic LPs
      were associated with a 69% relative improvement in survival, regardless of
      initial intracranial pressure. The role of therapeutic LPs should be reevaluated.

PMID- 25057103
TI  - Maternal diet and weight at 3 months postpartum following a pregnancy
      intervention with a low glycaemic index diet: results from the ROLO randomised
      control trial.
AB  - Pregnancy increases the risk of being overweight at a later time period,
      particularly when there is excessive gestational weight gain. There remains a
      paucity of data into the effect of low glycaemic index (GI) pregnancy
      interventions postpartum. AIM: To examine the impact of a low glycaemic index
      diet during pregnancy on maternal diet 3 months postpartum. METHODOLOGY: This
      analysis examined the diet, weight and lifestyle of 460 participants of the ROLO
      study 3 months postpartum. Questionnaires on weight, physical activity,
      breastfeeding, supplement use, food label reading and dietary habits were
      completed. RESULTS: The intervention group had significantly greater weight loss
      from pre-pregnancy to 3 months postpartum than the control group (1.3 vs. 0.1 kg,
      p = 0.022). The intervention group reported greater numbers following a low
      glycaemic index diet (p < 0.001) and reading food labels (p = 0.032) and had a
      lower glycaemic load (GL) (128 vs. 145, p = 0.014) but not GI (55 vs. 55, p =
      0.809) than controls. CONCLUSIONS: Low GI dietary interventions in pregnancy
      result in improved health-behaviours and continued reported compliance at 3
      months postpartum possibly through lower dietary GL as a result of portion
      control. Greater levels of weight loss from pre-pregnancy to 3 months postpartum
      in the intervention group may have important positive implications for overweight
      and obesity.

PMID- 25057104
TI  - Pinus densiflora Sieb. et Zucc. alleviates lipogenesis and oxidative stress
      during oleic acid-induced steatosis in HepG2 cells.
AB  - Excess accumulation of lipids and oxidative stress in the liver contribute to
      nonalcoholic fatty liver disease (NAFLD). We hypothesized that Pinus densiflora
      Sieb. et Zucc. (PSZ) can protect against NAFLD by regulating lipid accumulation
      and oxidative stress in the liver. To investigate the effect of PSZ upon NAFLD,
      we used an established cellular model: HepG2 cells treated with oleic acid. Then,
      the extent of hepatic steatosis and oxidative stress was assessed and levels of
      inflammatory markers measured. Oleic acid-treated HepG2 cells, compared with
      controls, had greater lipid accumulation. PSZ decreased lipid accumulation by 63%
      in oleic acid-treated HepG2 cells. Additionally, PSZ decreased the target gene
      expression of lipogenesis such as sterol regulatory element binding protein-1c,
      fatty acid synthase, stearoyl-CoA desaturase-1, diacylglycerol O-acyltransferase
      1, and acetyl-CoA carboxylase-1 by 1.75, 6.0, 2.32, 1.93 and 1.81 fold,
      respectively. In addition, Oleic acid-treated HepG2 cells elicited extensive
      accumulation of tumor necrosis factor-alpha (TNFalpha) by 4.53 fold, whereas PSZ
      treated cells decreased the expression of TNFalpha mRNA by 1.76 fold. PSZ
      significantly inhibited oxidative stress induced by reactive oxygen species.
      These results suggest that PSZ has effects on steatosis in vitro and further
      studies are needed in vivo to verify the current observations. 

PMID- 25057106
TI  - We are pleased to introduce this next volume of the Journal of Huntington's
      Disease. Introduction.

PMID- 25057105
TI  - The effect of Arthrospira platensis capsules on CD4 T-cells and antioxidative
      capacity in a randomized pilot study of adult women infected with human
      immunodeficiency virus not under HAART in Yaounde, Cameroon.
AB  - Dietary supplements are often used to improve the nutritional status of people
      living with HIV/AIDS (PLHIV). Arthrospira platensis (Asp), also known as
      Spirulina, is a cyanobacterium rich in proteins and micronutrients. Cell and
      animal trials described immune-modulating, antiretroviral and antioxidant
      activities. This pilot study describes the effects of the supplementation of 5
      g/day of Asp on a pre-highly-active antiretroviral therapy (pre-HAART), HIV
      infected, adult female population. It was conducted as a three-month randomized
      controlled trial (RCT) that compared a cup supplementation of five grams/day of
      Asp with a placebo of equal protein content and energy. The study included 73 HIV
      infected women. The immediate outcome variables were CD4 T-cells, viral load and
      immune activation by CD8 T-cells expressing CD38. The antioxidant status was
      assessed by way of the total antioxidant capacity of the serum (TAOS). The renal
      function was documented by way of creatinine, urea and the calculated glomerular
      filtration rate. Statistical analyses were carried out with non-parametric tests,
      and the effect size of each interaction was calculated. No differences in the
      immunological and virological markers between the Asp and the placebo group could
      be observed. In the placebo group, 21 of 30 patients (70%) developed concomitant
      events, while in the Asp group, only 12 of 28 patients (43%) did. Both groups
      registered a significant weight increase; 0.5 kg (p < 0.05) in the Asp group and
      0.65 kg (p < 0.05) in the placebo group. The antioxidant capacity increase of 56
      (1-98) uM for Asp was significantly different from the decrease observed in the
      placebo group (p < 0.001). A slight increase in the creatinine level of 0.1 g/dL
      (p < 0.001) was observed in the Asp group, and no effect was observed in the urea
      levels. The improvement of the antioxidant capacity under Asp, shown for the
      first time on PLHIV, could become a focus for future research on the nutritional
      and health effects of Spirulina. The observed slight, but significant increase of
      serum creatinine needs further evaluation, especially with varying doses of Asp. 

PMID- 25057108
TI  - Isolation of a circulating CD45-, CD34dim cell population and validation of their
      endothelial phenotype.
AB  - Accurately detecting circulating endothelial cells (CECs) is important since
      their enumeration has been proposed as a biomarker to measure injury to the
      vascular endothelium. However, there is no single methodology for determining
      CECs in blood, making comparison across studies difficult. Many methods for
      detecting CECs rely on characteristic cell surface markers and cell viability
      indicators, but lack secondary validation. Here, a CEC population in healthy
      adult human subjects was identified by flow cytometry as CD45-, CD34dim that is
      comparable to a previously described CD45-, CD31bright population. In addition,
      nuclear staining with 7-aminoactinomycin D (7-AAD) was employed as a standard
      technique to exclude dead cells. Unexpectedly, the CD45-, CD34dim, 7-AAD- CECs
      lacked surface detectable CD146, a commonly used marker of CECs. Furthermore,
      light microscopy revealed this cell population to be composed primarily of large
      cells without a clearly defined nucleus. Nevertheless, immunostains still
      demonstrated the presence of the lectin Ulex europaeus and von Willebrand factor.
      Ultramicro analytical immunochemistry assays for the endothelial cell proteins
      CD31, CD34, CD62E, CD105, CD141, CD144 and vWF indicated these cells possess an
      endothelial phenotype. However, only a small amount of RNA, which was mostly
      degraded, could be isolated from these cells. Thus the majority of CECs in
      healthy individuals as defined by CD45-, CD34dim, and 7-AAD- have shed their
      CD146 surface marker and are senescent cells without an identifiable nucleus and
      lacking RNA of sufficient quantity and quality for transcriptomal analysis. This
      study highlights the importance of secondary validation of CEC identification.

PMID- 25057109
TI  - oxLDL induces injury and defenestration of human liver sinusoidal endothelial
      cells via LOX1.
AB  - Non-alcoholic fatty liver disease is associated with hepatic microangiopathy and
      liver inflammation caused by type 2 diabetes mellitus. Oxidised LDL (oxLDL) is
      involved in proinflammatory and cytotoxic events in various microcirculatory
      systems. The lectin-like oxLDL receptor 1 (LOX1) plays a crucial role in oxLDL
      induced pathological transformation. However, the underlying mechanism of oxLDL's
      effects on liver microcirculation disturbances remains unclear. In this study, we
      investigated the effects of oxLDL on LOX1 (OLR1) expression and function, as well
      as on the fenestration features of human liver sinusoidal endothelial cells
      (HLSECs) in vitro. Primary HLSECs were obtained and cultured. The cells were
      treated with various concentrations of oxLDL (25, 50, 100 and 200  MUg/ml), and
      the cytotoxicity and expression of LOX1 were examined. Furthermore, LOX1
      knockdown was performed using siRNA technology, and the changes in intracellular
      reactive oxygen species (ROS), NFkappaB, p65, (p65), endothelin 1 (ET1 (EDN1)),
      eNOS (NOS3) and caveolin 1 (CAV1) levels were measured. Cells were treated with
      100  MUg/ml oxLDL, and the fenestra morphology was visualised using scanning
      electron microscopy. oxLDL significantly increased LOX1 expression at both the
      mRNA and protein levels in HLSECs in a dose- and time-dependent manner. oxLDL
      stimulation increased ROS generation and NFkappaB activation, upregulated ET1 and
      caveolin 1 expression, downregulated eNOS expression and reduced the fenestra
      diameter and porosity. All of these oxLDL-mediated effects were inhibited after
      LOX1 knockdown. These results reveal a mechanism by which oxLDL stimulates the
      production of LOX1 through the ROS/NFkappaB signalling pathway and by which LOX1
      mediates oxLDL-induced endothelial injury and the defenestration of HLSECs.

PMID- 25057110
TI  - Calcineurin and CRTC2 mediate FSH and TGFbeta1 upregulation of Cyp19a1 and Nr5a
      in ovary granulosa cells.
AB  - Estrogens are essential for female reproduction and overall well-being, and
      estrogens in the circulation are largely synthesized in ovarian granulosa cells.
      Using primary cultures of ovarian granulosa cells from gonadotropin-primed
      immature rats, we have recently discovered that pituitary FSH and ovarian
      cytokine transforming growth factor beta 1 (TGFbeta1) induce calcineurin-mediated
      dephosphorylation-activation of cAMP-response element-binding protein (CREB)
      regulated transcription coactivator (CRTC2) to modulate the expression of Star,
      Cyp11a1, and Hsd3b leading to increased production of progesterone. This study
      explored the role of calcineurin and CRTC2 in FSH and TGFbeta1 regulation of
      Cyp19a1 expression in granulosa cells. Ovarian granulosa cells treated with FSH
      displayed increased aromatase protein at 24  h post-treatment, which subsided by
      48  h, while TGFbeta1 acting through its type 1 receptor augmented the action of
      FSH with a greater and longer effects. It is known that the ovary-specific
      Cyp19a1 PII-promoter contains crucial response elements for CREB and nuclear
      receptor NR5A subfamily liver receptor homolog 1 (LRH1/NR5A2) and steroidogenic
      factor 1 (SF1/NR5A1), and that the Nr5a2 promoter also has a potential CREB
      binding site. Herein, we demonstrate that FSH+TGFbeta1 increased LRH1 and SF1
      protein levels, and their binding to the Cyp19a1 PII-promoter evidenced,
      determined by chromatin immunoprecipitation analysis. Moreover, pretreatment with
      calcineurin auto-inhibitory peptide (CNI) abolished the FSH+TGFbeta1-upregulated
      but not FSH-upregulated aromatase activity at 48  h, and the corresponding mRNA
      changes in Cyp19a1, and Nr5a2 and Nr5a1 at 24  h. In addition, FSH and TGFbeta1
      increased CRTC2 binding to the Cyp19a1 PII-promoter and Nr5a2 promoter at 24  h,
      with CREB bound constitutively. In summary, the results of this study indicate
      that calcineurin and CRTC2 have important roles in mediating FSH and TGFbeta1
      collateral upregulation of Cyp19a1 expression together with its transcription
      regulators Nr5a2 and Nr5a1 in ovarian granulosa cells.

PMID- 25057111
TI  - GWAS and drug targets.
AB  - BACKGROUND: Genome wide association studies (GWAS) have revealed a large number
      of links between genome variation and complex disease. Among other benefits, it
      is expected that these insights will lead to new therapeutic strategies,
      particularly the identification of new drug targets. In this paper, we evaluate
      the power of GWAS studies to find drug targets by examining how many existing
      drug targets have been directly 'rediscovered' by this technique, and the extent
      to which GWAS results may be leveraged by network information to discover known
      and new drug targets. RESULTS: We find that only a very small fraction of drug
      targets are directly detected in the relevant GWAS studies. We investigate two
      possible explanations for this observation. First, we find evidence of negative
      selection acting on drug target genes as a consequence of strong coupling with
      the disease phenotype, so reducing the incidence of SNPs linked to the disease.
      Second, we find that GWAS genes are substantially longer on average than drug
      targets and than all genes, suggesting there is a length related bias in GWAS
      results. In spite of the low direct relationship between drug targets and GWAS
      reported genes, we found these two sets of genes are closely coupled in the human
      protein network. As a consequence, machine-learning methods are able to recover
      known drug targets based on network context and the set of GWAS reported genes
      for the same disease. We show the approach is potentially useful for identifying
      drug repurposing opportunities. CONCLUSIONS: Although GWA studies do not directly
      identify most existing drug targets, there are several reasons to expect that new
      targets will nevertheless be discovered using these data. Initial results on drug
      repurposing studies using network analysis are encouraging and suggest directions
      for future development.

PMID- 25057112
TI  - Clinical risk stratification optimizes value of biomarkers to predict new-onset
      heart failure in a community-based cohort.
AB  - BACKGROUND: We aim to identify and quantify the value of biomarkers for incident
      new-onset heart failure (HF) in a community-based cohort and subgroups based on
      cardiovascular risk and evaluate the prognostic value of 13 biomarkers for HF
      with reduced and preserved ejection fraction. METHODS AND RESULTS: Thirteen
      biomarkers reflecting diverse pathophysiologic domains were examined in 8569 HF
      free participants in Prevention of Vascular and Renal Endstage Disease (mean age,
      49 years; 50% men). Subjects were categorized in 2 risk groups based on
      cardiovascular history. Incremental value per biomarker was assessed using
      Harrell C-indices. One hundred sixty-eight subjects (2.4%) were diagnosed with
      new-onset HF in the low-risk group (n=6915; Framingham Risk Score, 5.9%) and 206
      (12.2%) subjects in the high-risk group (n=1654; Framingham Risk Score, 18.6%).
      The association of natriuretic peptides, adrenomedullin, endothelin, and galectin
      3 with new-onset HF was stronger in the high-risk group (all P<0.05). Troponin-T,
      high-sensitive C-reactive protein, urinary albumin excretion, and cystatin-C had
      similar risk for new-onset HF between both risk groups. The best model for new
      onset HF included the combination of N-terminal pro-B-type natriuretic peptide,
      troponin-T, and urinary albumin excretion, increasing model accuracy to 0.81
      (9.5%, P<0.001) in the high-risk group. Except for a modest effect of cystatin-C,
      no biomarker was associated with increased risk for HF with preserved ejection
      fraction. CONCLUSIONS: Risk stratification increases the incremental value per
      biomarker to predict new-onset HF, especially HF with reduced ejection fraction.
      We suggest that routine biomarker testing should be limited to the use of
      natriuretic peptides and troponin-T in patients with increased cardiovascular
      risk.

PMID- 25057113
TI  - [Glial fibrillary acidic protein in patients with symptoms of acute stroke:
      diagnostic marker of cerebral hemorrhage].
AB  - Glial fibrillary acidic protein (GFAP) is a highly brain-specific protein that is
      expressed in large quantities in astrocytes and has important functions in terms
      of maintaining and stabilizing the cytoskeleton. Acute intracerebral hemorrhage
      leads to an immediate mechanical destruction of astroglial cells with the
      subsequent release of GFAP into the extracellular space and the bloodstream. On
      the other hand, necrosis, cytolysis and GFAP release does not occur before 6-12 h
      after symptom onset in ischemic stroke. Thus, in the early hours after stroke
      increased GFAP values could indicate intracerebral hemorrhage. This review
      article describes the underlying pathophysiology of the test and guides the
      reader through the available data. Potential implications regarding the
      prehospital triage of acute stroke patients are discussed, including the
      possibility to initiate hyperacute treatment, such as blood pressure reduction in
      patients with intracerebral hemorrhage. Other areas of interest for a potential
      GFAP test include traumatic brain injury and malignant gliomas.

PMID- 25057114
TI  - A novel mutation in ADAMTS13 of a child with Upshaw-Schulman Syndrome.

PMID- 25057115
TI  - Randall Selitto pressure algometry for assessment of bone-related pain in rats.
AB  - BACKGROUND: Deep pain is neglected compared with cutaneous sources. Pressure
      algometry has been validated in the clinic for assessment of bone-related pain in
      humans. In animal models of bone-related pain, we have validated the Randall
      Selitto behavioural test for assessment of acute and pathological bone pain and
      compared the outcome with more traditional pain-related behaviour measures.
      METHODS: Randall Selitto pressure algometry was performed over the anteromedial
      part of the tibia in naive rats, sham-operated rats, and rats inoculated with
      MRMT-1 carcinoma cells in the left tibia, and the effect of morphine was
      investigated. Randall Selitto measures of cancer-induced bone pain were
      supplemented by von Frey testing, weight-bearing and limb use test. Contribution
      of cutaneous nociception to Randall Selitto measures were examined by local
      anaesthesia. RESULTS: Randall Selitto pressure algometry over the tibia resulted
      in reproducible withdrawal thresholds, which were dose-dependently increased by
      morphine. Cutaneous nociception did not contribute to Randall Selitto measures.
      In cancer-bearing animals, compared with sham, significant differences in pain
      related behaviours were demonstrated by the Randall Selitto test on day 17 and 21
      post-surgery. A difference was also demonstrated by von Frey testing, weight
      bearing and limb use tests. CONCLUSION: Our results indicate that pressure
      applied by the Randall Selitto algometer on a region, where the bone is close to
      the skin, may offer a way to measure bone-related pain in animal models and could
      provide a supplement to the traditional behavioural tests and a means to study
      deep pain.

PMID- 25057117
TI  - Is claviculo pro humeri of value for limb salvage of pediatric proximal humerus
      sarcomas?
AB  - BACKGROUND: There are several options for proximal humerus reconstruction in
      young children after resection of a malignant tumor and no one technique has been
      definitively shown to be superior to others, leaving the decision to surgeon and
      patient choice. Claviculo pro humeri (CPH) is a biologic reconstruction of the
      proximal humerus using the patient's ipsilateral clavicle as a rotational osseous
      flap. CPH represents a potential option for this complicated clinical problem in
      very young children, but little is known about it because the indications for its
      use are so uncommon. QUESTIONS/PURPOSES: The purposes of this study were to (1)
      assess the oncologic outcomes of CPH at a minimum of 2 years in a small series of
      patients; (2) elicit the complications associated with this procedure; and (3)
      show the Musculoskeletal Tumor Society (MSTS) functional score of these patients.
      METHODS: Four patients (average age, 5 years 11 months; range, 4 years 5 months
      to 8 years 9 months at the time of surgery) were treated with CPH for
      reconstruction after resection of a proximal humerus sarcoma; this represented
      all of the patients treated with this approach for this problem between January
      2008 and April 2011 at one institution. During this period, the general
      indications for using CPH were the need to reconstruct a proximal humerus defect
      in a child younger than 10 years of age. During this time, CPH was used for all
      patients treated for proximal humerus sarcomas meeting these criteria. Patient
      demographics, diagnosis, tumor size and extent, operative details, radiographs
      and MRIs, complications, and functional outcomes were assessed. RESULTS: All are
      alive with no evidence of disease at a minimum followup of 31 months (average, 43
      months; range, 31-58 months). Two patients developed nonunion and underwent
      revision surgery. Osseous union and a stable neoshoulder articulation were
      ultimately obtained in all patients. Limited shoulder motion was the only
      functional deficit noted with forward elevation ranging between 30 degrees  and
      90 degrees . MSTS functional scores were excellent with a range of 87% to 90%.
      CONCLUSIONS: This is a rarely used procedure in North America but we achieved
      functional limb salvage in all four patients. Consistent with prior literature,
      nonunion was the major complication in this series. The two nonunions were
      successfully treated without interruption of chemotherapy or significant bone
      graft donor site morbidity. Based on these results, the authors suggest that this
      procedure is a reasonable reconstruction option to consider after proximal
      humerus resection in patients younger than 10 years of age. Further followup will
      be required to assess long-term results and to determine how this procedure
      compares with the alternatives. LEVEL OF EVIDENCE: Level IV, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 25057116
TI  - What Are Long-term Predictors of Outcomes for Lumbar Disc Herniation? A
      Randomized and Observational Study.
AB  - BACKGROUND: Although previous studies have illustrated improvements in surgical
      cohorts for patients with intervertebral disc herniation, there are limited data
      on predictors of long-term outcomes comparing surgical and nonsurgical outcomes.
      QUESTIONS/PURPOSES: We assessed outcomes of operative and nonoperative treatment
      for patients with intervertebral disc herniation and symptomatic radiculopathy at
      8 years from the Spine Patient Outcomes Research Trial. We specifically examined
      subgroups to determine whether certain populations had a better long-term outcome
      with surgery or nonoperative treatment. METHODS: Patients with symptomatic lumbar
      radiculopathy for at least 6 weeks associated with nerve root irritation or
      neurologic deficit on examination and a confirmed disc herniation on cross
      sectional imaging were enrolled at 13 different clinical sites. Patients
      consenting to participate in the randomized cohort were assigned to surgical or
      nonoperative treatment using variable permuted block randomization stratified by
      site. Those who declined randomization entered the observational cohort group
      based on treatment preference but were otherwise treated and followed identically
      to the randomized cohort. Of those in the randomized cohort, 309 of 501 (62%)
      provided 8-year data and in the observational group 469 of 743 (63%). Patients
      were treated with either surgical discectomy or usual nonoperative care. By 8
      years, only 148 of 245 (60%) of those randomized to surgery had undergone
      surgery, whereas 122 of 256 (48%) of those randomized to nonoperative treatment
      had undergone surgery. The primary outcome measures were SF-36 bodily pain, SF-36
      physical function, and Oswestry Disability Index collected at 6 weeks, 3 months,
      6 months, 12 months, and then annually. Further analysis studied the following
      factors to determine if any were predictive of long-term outcomes: sex,
      herniation location, depression, smoking, work status, other joint problems,
      herniation level, herniation type, and duration of symptoms. RESULTS: The intent
      to-treat analysis of the randomized cohort at 8 years showed no difference
      between surgical and nonoperative treatment for the primary outcome measures.
      Secondary outcome measures of sciatica bothersomeness, leg pain, satisfaction
      with symptoms, and self-rated improvement showed greater improvement in the group
      randomized to surgery despite high levels of crossover. The as-treated analysis
      of the combined randomized and observational cohorts, adjusted for potential
      confounders, showed advantages for surgery for all primary outcome measures;
      however, this has the potential for confounding from other unrecognized
      variables. Smokers and patients with depression or comorbid joint problems had
      worse functional outcomes overall (with surgery and nonoperative care) but
      similar surgical treatment effects. Patients with sequestered fragments, symptom
      duration greater than 6 months, those with higher levels of low back pain, or who
      were neither working nor disabled at baseline showed greater surgical treatment
      effects. CONCLUSIONS: The intent-to-treat analysis, which is complicated by high
      rates of crossover, showed no difference over 8 years for primary outcomes of
      overall pain, physical function, and back-related disability but did show small
      advantages for secondary outcomes of sciatica bothersomeness, satisfaction with
      symptoms, and self-rated improvement. Subgroup analyses identified those groups
      with sequestered fragments on MRI, higher levels of baseline back pain
      accompanying radiculopathy, a longer duration of symptoms, and those who were
      neither working nor disabled at baseline with a greater relative advantage from
      surgery at 8 years. LEVEL OF EVIDENCE: Level II, therapeutic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 25057107
TI  - beta-Defensin genomic copy number does not influence the age of onset in
      Huntington's Disease.
AB  - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative
      disorder caused by the abnormal expansion of a CAG triplet repeat tract in the
      huntingtin gene. While the length of this CAG expansion is the major determinant
      of the age of onset (AO), other genetic factors have also been shown to play a
      modulatory role. Recent evidence suggests that neuroinflammations is a pivotal
      factor in the pathogenesis of HD, and that targeting this process may have
      important therapeutic ramifications. The human beta-defensin 2 (hBD2)- encoded by
      DEFB4- is an antimicrobial peptide that exhibits inducible expression in
      astrocytes during inflammation and is an important regulator of innate and
      adaptive immune response. Therefore, DEFB4 may contribute to the
      neuroinflammatory processes observed in HD. OBJECTIVE: In this study we tested
      the hypothesis that copy number variation (CNV) of the beta-defensin region,
      including DEFB4, modifies the AO in HD. METHODS AND RESULTS: We genotyped beta
      defensin CNV in 490 HD individuals using the paralogue ratio test and found no
      association between beta-defensin CNV and onset of HD. CONCLUSIONS: We conclude
      that it is unlikely that DEFB4 plays a role in HD pathogenesis.

PMID- 25057118
TI  - Feature-based multiple models improve classification of mutation-induced
      stability changes.
AB  - BACKGROUND: Reliable prediction of stability changes in protein variants is an
      important aspect of computational protein design. A number of machine learning
      methods that allow a classification of stability changes knowing only the
      sequence of the protein emerged. However, their performance on amino acid
      substitutions of previously unseen non-homologous proteins is rather limited.
      Moreover, the performance varies for different types of mutations based on the
      secondary structure or accessible surface area of the mutation site. RESULTS: We
      proposed feature-based multiple models with each model designed for a specific
      type of mutations. The new method is composed of five models trained for
      mutations in exposed, buried, helical, sheet, and coil residues. The
      classification of a mutation as stabilising or destabilising is made as a
      consensus of two models, one selected based on the predicted accessible surface
      area and the other based on the predicted secondary structure of the mutation
      site. We refer to our new method as Evolutionary, Amino acid, and Structural
      Encodings with Multiple Models (EASE-MM). Cross-validation results show that EASE
      MM provides a notable improvement to our previous work reaching a Matthews
      correlation coefficient of 0.44. EASE-MM was able to correctly classify 73% and
      75% of stabilising and destabilising protein variants, respectively. Using an
      independent test set of 238 mutations, we confirmed our results in a comparison
      with related work. CONCLUSIONS: EASE-MM not only outperformed other related
      methods but achieved more balanced results for different types of mutations based
      on the accessible surface area, secondary structure, or magnitude of stability
      changes. This can be attributed to using multiple models with the most relevant
      features selected for the given type of mutations. Therefore, our results support
      the presumption that different interactions govern stability changes in the
      exposed and buried residues or in residues with a different secondary structure.

PMID- 25057119
TI  - A web-based peer-modeling intervention aimed at lifestyle changes in patients
      with coronary heart disease and chronic back pain: sequential controlled trial.
AB  - BACKGROUND: Traditional secondary prevention programs often fail to produce
      sustainable behavioral changes in everyday life. Peer-modeling interventions and
      integration of peer experiences in health education are a promising way to
      improve long-term effects in behavior modification. However, effects of peer
      support modeling on behavioral change have not been evaluated yet. Therefore, we
      implemented and evaluated a website featuring patient narratives about successful
      lifestyle changes. OBJECTIVE: Our aim is to examine the effects of using Web
      based patient narratives about successful lifestyle change on improvements in
      physical activity and eating behavior for patients with coronary heart disease
      and chronic back pain 3 months after participation in a rehabilitation program.
      METHODS: The lebensstil-aendern ("lifestyle-change") website is a nonrestricted,
      no-cost, German language website that provides more than 1000 video, audio, and
      text clips from interviews with people with coronary heart disease and chronic
      back pain. To test efficacy, we conducted a sequential controlled trial and
      recruited patients with coronary heart disease and chronic back pain from 7
      inpatient rehabilitation centers in Germany. The intervention group attended a
      presentation on the website; the control group did not. Physical activity and
      eating behavior were assessed by questionnaire during the rehabilitation program
      and 12 weeks later. Analyses were conducted based on an intention-to-treat and an
      as-treated protocol. RESULTS: A total of 699 patients were enrolled and 571 cases
      were included in the analyses (control: n=313, intervention: n=258; female:
      51.1%, 292/571; age: mean 53.2, SD 8.6 years; chronic back pain: 62.5%, 357/571).
      Website usage in the intervention group was 46.1% (119/258). In total, 141 trial
      participants used the website. Independent t tests based on the intention-to
      treat protocol only demonstrated nonsignificant trends in behavioral change
      related to physical activity and eating behavior. Multivariate regression
      analyses confirmed belonging to the intervention group was an independent
      predictor of self-reported improvements in physical activity regularity
      (beta=.09, P=.03) and using less fat for cooking (beta=.09, P=.04). In
      independent t tests based on the as-treated protocol, website use was associated
      with higher self-reported improvements in integrating physical activity into
      daily routine (d=0.22, P=.02), in physical activity regularity (d=0.23, P=.02),
      and in using less fat for cooking (d=0.21, P=.03). Multivariate regression
      analyses revealed that using the website at least 3 times was the only factor
      associated with improved lifestyle behaviors. CONCLUSIONS: Usage of the
      lebensstil-aendern website corresponds to more positive lifestyle changes.
      However, as-treated analyses do not allow for differentiating between causal
      effects and selection bias. Despite these limitations, the trial indicates that
      more than occasional website usage is necessary to reach dose-response efficacy.
      Therefore, future studies should concentrate on strategies to improve adherence
      to Web-based interventions and to encourage more frequent usage of these
      programs.

PMID- 25057121
TI  - NeEMO: a method using residue interaction networks to improve prediction of
      protein stability upon mutation.
AB  - BACKGROUND: The rapid growth of un-annotated missense variants poses challenges
      requiring novel strategies for their interpretation. From the thermodynamic point
      of view, amino acid changes can lead to a change in the internal energy of a
      protein and induce structural rearrangements. This is of great relevance for the
      study of diseases and protein design, justifying the development of prediction
      methods for variant-induced stability changes. RESULTS: Here we propose NeEMO, a
      tool for the evaluation of stability changes using an effective representation of
      proteins based on residue interaction networks (RINs). RINs are used to extract
      useful features describing interactions of the mutant amino acid with its
      structural environment. Benchmarking shows NeEMO to be very effective, allowing
      reliable predictions in different parts of the protein such as beta-strands and
      buried residues. Validation on a previously published independent dataset shows
      that NeEMO has a Pearson correlation coefficient of 0.77 and a standard error of
      1 Kcal/mol, outperforming nine recent methods. The NeEMO web server can be freely
      accessed from URL: http://protein.bio.unipd.it/neemo/. CONCLUSIONS: NeEMO offers
      an innovative and reliable tool for the annotation of amino acid changes. A key
      contribution are RINs, which can be used for modeling proteins and their
      interactions effectively. Interestingly, the approach is very general, and can
      motivate the development of a new family of RIN-based protein structure
      analyzers. NeEMO may suggest innovative strategies for bioinformatics tools
      beyond protein stability prediction.

PMID- 25057122
TI  - Intervention use and action planning in a web-based computer-tailored weight
      management program for overweight adults: randomized controlled trial.
AB  - BACKGROUND: There are many online interventions aiming for health behavior change
      but it is unclear how such interventions and specific planning tools are being
      used. OBJECTIVE: The aim of this study is to identify which user characteristics
      were associated with use of an online, computer-tailored self-regulation
      intervention aimed at prevention of weight gain; and to examine the quality of
      the goals and action plans that were generated using the online planning tools.
      METHODS: Data were obtained with a randomized controlled effect evaluation trial
      in which the online computer-tailored intervention was compared to a website
      containing generic information about prevention of weight gain. The tailored
      intervention included self-regulation techniques such as personalized feedback,
      goal setting, action planning, monitoring, and other techniques aimed at weight
      management. Participants included 539 overweight adults (mean age 46.9 years,
      mean body mass index [BMI] 28.03 kg/m(2), 31.2% male, 11% low education level)
      recruited from the general population. Use of the intervention and its planning
      tools were derived from server registration data. Physical activity, fat intake,
      motivational factors, and self-regulation skills were self-reported at baseline.
      Descriptive analyses and logistic regression analyses were used to analyze the
      results. RESULTS: Use of the tailored intervention decreased sharply after the
      first modules. Visiting the first tailored intervention module was more likely
      among participants with low levels of fat intake (OR 0.77, 95% CI 0.62-0.95) or
      planning for change in PA (OR 0.23, 95% CI 0.05-0.97). Revisiting the
      intervention was more likely among participants high in restrained eating (OR
      2.45, 95% CI 1.12-5.43) or low in proactive coping skills for weight control (OR
      0.28, 95% CI 0.10-0.76). The planning tools were used by 5%-55% of the
      participants, but only 20%-75% of the plans were of good quality. CONCLUSIONS:
      This study showed that psychological factors such as self-regulation skills and
      action planning were associated with repeated use of an online, computer-tailored
      self-regulation intervention aimed at prevention of weight gain among adults
      being overweight. Use of the intervention was not optimal, with a limited number
      of participants who visited all the intervention modules. The use of the action
      and coping planning components of the intervention was mediocre and the quality
      of the generated plans was low, especially for the coping plans. It is important
      to identify how the use of action planning and coping planning components in
      online interventions can be promoted and how the quality of plans generated
      through these tools can be improved. TRIAL REGISTRATION: Netherlands Trial
      Register: NTR1862; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1862
      (Archived by WebCite at http://www.webcitation.org/6QG1ZPIzZ).

PMID- 25057125
TI  - Expansion of the clinical phenotype associated with mutations in activity
      dependent neuroprotective protein.

PMID- 25057127
TI  - Esm1 modulates endothelial tip cell behavior and vascular permeability by
      enhancing VEGF bioavailability.
AB  - RATIONALE: Endothelial cell-specific molecule 1 (Esm1) is a secreted protein
      thought to play a role in angiogenesis and inflammation. However, there is
      currently no direct in vivo evidence supporting a function of Esm1 in either of
      these processes. OBJECTIVE: To determine the role of Esm1 in vivo and the
      underlying molecular mechanisms. METHODS AND RESULTS: We generated and analyzed
      Esm1 knockout (Esm1(KO)) mice to study its role in angiogenesis and inflammation.
      Esm1 expression is induced by the vascular endothelial growth factor A (VEGF-A)
      in endothelial tip cells of the mouse retina. Esm1(KO) mice showed delayed
      vascular outgrowth and reduced filopodia extension, which are both VEGF-A
      dependent processes. Impairment of Esm1 function led to a decrease in
      phosphorylated Erk1/2 (extracellular-signal regulated kinases 1/2) in sprouting
      vessels. We also found that Esm1(KO) mice displayed a 40% decrease in leukocyte
      transmigration. Moreover, VEGF-induced vascular permeability was decreased by 30%
      in Esm1(KO) mice and specifically on stimulation with VEGF-A165 but not VEGF
      A121. Accordingly, cerebral edema attributable to ischemic stroke-induced
      vascular permeability was reduced by 50% in the absence of Esm1. Mechanistically,
      we show that Esm1 binds directly to fibronectin and thereby displaces fibronectin
      bound VEGF-A165 leading to increased bioavailability of VEGF-A165 and
      subsequently enhanced levels of VEGF-A signaling. CONCLUSIONS: Esm1 is
      simultaneously a target and modulator of VEGF signaling in endothelial cells,
      playing a role in angiogenesis, inflammation, and vascular permeability, which
      might be of potential interest for therapeutic applications.

PMID- 25057128
TI  - Brain editorial.

PMID- 25057126
TI  - Meta-analysis identifies loci affecting levels of the potential osteoarthritis
      biomarkers sCOMP and uCTX-II with genome wide significance.
AB  - BACKGROUND: Research for the use of biomarkers in osteoarthritis (OA) is
      promising, however, adequate discrimination between patients and controls may be
      hampered due to innate differences. We set out to identify loci influencing
      levels of serum cartilage oligomeric protein (sCOMP) and urinary C-telopeptide of
      type II collagen (uCTX-II). METHODS: Meta-analysis of genome-wide association
      studies was applied to standardised residuals of sCOMP (N=3316) and uCTX-II
      (N=4654) levels available in 6 and 7 studies, respectively, from TreatOA. Effects
      were estimated using a fixed-effects model. Six promising signals were followed
      up by de novo genotyping in the Cohort Hip and Cohort Knee study (N = 964).
      Subsequently, their role in OA susceptibility was investigated in large-scale
      genome-wide association studies meta-analyses for OA. Differential expression of
      annotated genes was assessed in cartilage. RESULTS: Genome-wide significant
      association with sCOMP levels was found for a SNP within MRC1 (rs691461, p = 1.7
      * 10(-12)) and a SNP within CSMD1 associated with variation in uCTX-II levels
      with borderline genome-wide significance (rs1983474, p = 8.5 * 10(-8)).
      Indication for association with sCOMP levels was also found for a locus close to
      the COMP gene itself (rs10038, p = 7.1 * 10(-6)). The latter SNP was subsequently
      found to be associated with hip OA whereas COMP expression appeared responsive to
      the OA pathophysiology in cartilage. CONCLUSIONS: We have identified genetic loci
      affecting either uCTX-II or sCOMP levels. The genome wide significant association
      of MRC1 with sCOMP levels was found likely to act independent of OA subtypes.
      Increased sensitivity of biomarkers with OA may be accomplished by taking genetic
      variation into account.

PMID- 25057129
TI  - On the modelling of seizure dynamics.

PMID- 25057130
TI  - Calcium currents regulate dopamine autoreceptors.

PMID- 25057131
TI  - Glycine receptor antibodies in PERM: a new channelopathy.

PMID- 25057132
TI  - Towards network substrates of brain disorders.

PMID- 25057134
TI  - An analysis of electrical impedance measurements applied for plant N status
      estimation in lettuce (Lactuca sativa).
AB  - Nitrogen plays a key role in crop yields. Hence, farmers may apply excessive N
      fertilizers to crop fields, inducing environmental pollution. Crop N monitoring
      methods have been developed to improve N fertilizer management, most of them
      based on leaf or canopy optical-property measurements. However, sensitivity to
      environmental interference remains an important drawback. Electrical impedance
      has been applied to determine the physiological and nutritional status of plant
      tissue, but no studies related to plant-N contents are reported. The objective of
      this article is to analyze how the electrical impedance response of plants is
      affected by their N status. Four sets of lettuce (Lactuca sativa L.) with a
      different N-source concentrations per set were used. Total nitrogen and
      electrical impedance spectra (in a 1 to 100 kHz frequency range) were measured
      five times per set, three times every other day. Minimum phase angles of
      impedance spectra were detected and analyzed, together with the frequency value
      in which they occurred, and their magnitude at that frequency. High and positive
      correlation was observed between plant N content and frequency values at minimum
      phase angle with no significant variations detected between days of measurement.
      These results suggest that electrical impedance can be sensitive to plant N
      status. 

PMID- 25057133
TI  - The hubs of the human connectome are generally implicated in the anatomy of brain
      disorders.
AB  - Brain networks or 'connectomes' include a minority of highly connected hub nodes
      that are functionally valuable, because their topological centrality supports
      integrative processing and adaptive behaviours. Recent studies also suggest that
      hubs have higher metabolic demands and longer-distance connections than other
      brain regions, and therefore could be considered biologically costly. Assuming
      that hubs thus normally combine both high topological value and high biological
      cost, we predicted that pathological brain lesions would be concentrated in hub
      regions. To test this general hypothesis, we first identified the hubs of brain
      anatomical networks estimated from diffusion tensor imaging data on healthy
      volunteers (n = 56), and showed that computational attacks targeted on hubs
      disproportionally degraded the efficiency of brain networks compared to random
      attacks. We then prepared grey matter lesion maps, based on meta-analyses of
      published magnetic resonance imaging data on more than 20 000 subjects and 26
      different brain disorders. Magnetic resonance imaging lesions that were common
      across all brain disorders were more likely to be located in hubs of the normal
      brain connectome (P < 10(-4), permutation test). Specifically, nine brain
      disorders had lesions that were significantly more likely to be located in hubs
      (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease.
      Both these disorders had significantly hub-concentrated lesion distributions,
      although (almost completely) distinct subsets of cortical hubs were lesioned in
      each disorder: temporal lobe hubs specifically were associated with higher lesion
      probability in Alzheimer's disease, whereas in schizophrenia lesions were
      concentrated in both frontal and temporal cortical hubs. These results linking
      pathological lesions to the topological centrality of nodes in the normal
      diffusion tensor imaging connectome were generally replicated when hubs were
      defined instead by the meta-analysis of more than 1500 task-related functional
      neuroimaging studies of healthy volunteers to create a normative functional co
      activation network. We conclude that the high cost/high value hubs of human brain
      networks are more likely to be anatomically abnormal than non-hubs in many (if
      not all) brain disorders. 

PMID- 25057135
TI  - Vertical soil profiling using a galvanic contact resistivity scanning approach.
AB  - Proximal sensing of soil electromagnetic properties is widely used to map spatial
      land heterogeneity. The mapping instruments use galvanic contact, capacitive
      coupling or electromagnetic induction. Regardless of the type of instrument, the
      geometrical configuration between signal transmitting and receiving elements
      typically defines the shape of the depth response function. To assess vertical
      soil profiles, many modern instruments use multiple transmitter-receiver pairs.
      Alternatively, vertical electrical sounding can be used to measure changes in
      apparent soil electrical conductivity with depth at a specific location. This
      paper examines the possibility for the assessment of soil profiles using a
      dynamic surface galvanic contact resistivity scanning approach, with transmitting
      and receiving electrodes configured in an equatorial dipole-dipole array. An
      automated scanner system was developed and tested in agricultural fields with
      different soil profiles. While operating in the field, the distance between
      current injecting and measuring pairs of rolling electrodes was varied
      continuously from 40 to 190 cm. The preliminary evaluation included a comparison
      of scan results from 20 locations to shallow (less than 1.2 m deep) soil profiles
      and to a two-layer soil profile model defined using an electromagnetic induction
      instrument. 

PMID- 25057136
TI  - Detecting cannabis use on the human skin surface via an electronic nose system.
AB  - The most commonly used drug testing methods are based on the analysis of hair and
      urine using gas chromatography-mass spectrometry, liquid chromatography-mass
      spectrometry or immunoassay screening. These methods are time-consuming and
      partly expensive. One alternative method could be the application of an
      "electronic nose" (eNose). We have developed an eNose to detect directly on the
      human skin surface metabolic changes in the human body odor caused by cannabis
      consumption. Twenty cannabis-smoking and 20 tobacco-smoking volunteers were
      enrolled in this study. For the sensor signal data processing, two different
      methods were applied: Principle component analysis (PCA) with discriminant
      analysis, and the method of pattern recognition with subsequent support vector
      machines (SVM) processing. The PCA analysis achieved a correct classification of
      70%, whereas the SVM obtained an accuracy of 92.5% (sensitivity 95%, specificity
      90%) between cannabis-consuming volunteers and tobacco-smoking subjects. This
      study shows evidence that a low-cost, portable and fast-working eNose system
      could be useful for health protection, security agencies and for forensic
      investigations. The ability to analyze human body odor with an eNose opens up a
      wide field for diagnosing other drugs and also various diseases. 

PMID- 25057137
TI  - The optical property of core-shell nanosensors and detection of atrazine based on
      localized surface plasmon resonance (LSPR) sensing.
AB  - Three different nanosensors with core-shell structures were fabricated by
      molecular self-assembly and evaporation techniques. Such closely packed
      nanoparticles exhibit fine optical properties which are useful for biochemical
      sensing. The refractive index sensitivity (RIS) of nanosensors was detected by
      varying the refractive index of the surrounding medium and the decay length of
      nanosensors was investigated using a layer-by-layer polyelectrolyte multilayer
      assembly. The results showed that the thickness of the Au shell plays an
      important role in determining the RIS and the decay length. A system based on
      localized surface plasmon resonances (LSPR) sensing was constructed in our study.
      The core-shell nanosensors can detect 10 ng/mL atrazine solutions and are
      suitable for pesticide residue detection. 

PMID- 25057138
TI  - Strategy for making a superior Quenchbody to proteins: effect of the fluorophore
      position.
AB  - Antibody-based sensors have made outstanding contributions to the fields of
      molecular biology and biotechnology. Our group recently developed a novel
      powerful fluorescent immunosensor strategy named Quenchbody (Q-body), which has
      been applied to the detection of a range of antigens in a rapid, simple, and
      sensitive manner. However, there were some Q-bodies whose fluorescence response
      was limited, especially for detecting protein antigens. With the aim of improving
      this issue, here we made twelve types of Q-bodies incorporated with different
      number and position of TAMRA fluorophore in the single chain Fv of HyHEL-10, an
      anti-hen egg lysozyme antibody, as a model. By measuring the fluorescence
      intensity and its antigen dependency, it was revealed that VL-VH type Q-bodies
      labeled at a non-CDR loop region of the VL shows the highest fluorescence
      response. This position locates close to the quenching Trp35 in VL, while it is
      far from Trp residues in the bound antigen. This result clearly suggests the
      importance of dye position to maximize the fluorescence quenching and antigen
      dependent de-quenching. The discovery may open a way to make many other Q-bodies
      with superior response. 

PMID- 25057139
TI  - Enhanced response of a proteinase K-based conductometric biosensor using
      nanoparticles.
AB  - Proteinases are involved in a multitude of important physiological processes,
      such as protein metabolism. For this reason, a conductometric enzyme biosensor
      based on proteinase K was developed using two types of nanoparticles (gold and
      magnetic). The enzyme was directly adsorbed on negatively charged nanoparticles
      and then deposited and cross-linked on a planar interdigitated electrode (IDE).
      The biosensor was characterized with bovine serum albumin (BSA) as a standard
      protein. Higher sensitivity was obtained using gold nanoparticles. The linear
      range for BSA determination was then from 0.5 to 10 mg/L with a maximum response
      of 154 us. These results are greater than that found without any nanoparticles
      (maximum response of 10 us). The limit of detection (LOD) was 0.3 mg/L. An inter
      sensor reproducibility of 3.5% was obtained. 

PMID- 25057140
TI  - Effects of a live educational music therapy intervention on acute psychiatric
      inpatients' perceived social support and trust in the therapist: a four-group
      randomized effectiveness study.
AB  - BACKGROUND: Social support is associated with enhanced illness management and
      recovery in persons with mental illness, making it an important topic addressed
      through acute inpatient psychoeducational programs. In addition, trust in the
      therapist may mediate clinical outcomes in this patient population. To date, few
      studies have examined the effect of music-based psychoeducational programs on
      these variables. PURPOSE: The purpose of this study was to isolate and examine
      the component parts of a live educational music therapy intervention, and its
      effect on acute psychiatric inpatients' perceived social support from significant
      others, family, and friends and trust in the therapist. This study also explored
      whether trust in therapist varied across conditions, but did not examine it as a
      mediator for social support. METHOD: Participants (N = 96) were cluster
      randomized in a single-session posttest-only design to one of four conditions:
      live educational music therapy, recorded educational music therapy, education
      without music, or recreational music therapy without education. Conditions were
      designed to isolate the following intervention components: live vs. recorded
      music, educational vs. non-educational content, and music vs. nonmusic modality.
      Dependent measures were assessed post intervention via established self-report
      instruments evaluating perceived social support and trust in the therapist.
      RESULTS: There were no significant between-group differences for social support
      or trust in therapist total scores. However, subscale score analyses revealed two
      significant between-group differences: (a) participants in the Live Educational
      Music Therapy condition reported significantly higher perceived therapist
      competence compared with the Recorded Educational Music Therapy condition; (b)
      participants in the Live Educational Music Therapy condition reported
      significantly higher perceived support from friends compared with the
      Recreational Music Therapy condition. CONCLUSIONS: Live educational music therapy
      may be a way to heighten psychiatric inpatients' perceived social support
      concerning friends and perceptions of the therapist's competence. The current
      results demonstrated differences between live and recorded music therapy in
      psychiatric music therapy and provide empirical support for competent
      musicianship. Implications for clinical practice, limitations, and suggestions
      for future research are included.

PMID- 25057141
TI  - Novel Totally Laparoscopic Endolumenal Rectal Resection With Transanal Natural
      Orifice Specimen Extraction (NOSE) Without Rectal Stump Opening: A Modification
      of Our Recently Published Clean Surgical Technique in a Porcine Model.
AB  - Our group has recently described a novel technique for clean endolumenal bowel
      resection, in which abdominal and transanal approaches were used. In the current
      study, 2 modifications of this procedure were tested for feasibility in a porcine
      model. A laparoscopic approach to the peritoneal cavity was employed in rectal
      mobilization; this was followed by a transanal rectorectal intussusception and
      pull-through (IPT). IPT was established in a stepwise fashion. First, the
      proximal margin of resection was attached to the shaft of the anvil of an end-to
      end circular stapler with a ligature around the rectum. Second, this complex was
      pulled transanally to produce IPT. Once IPT was established, a second ligature
      was placed around the rectum approximating the proximal and distal resection
      margins. This was followed by a purse string suture through 2 bowel walls,
      encircling the shaft of the anvil just proximal to the ligatures. The specimen
      was resected and extracted by making a full-thickness incision through the 2
      bowel walls distal to the previously placed purse string suture and ligatures.
      The anastomosis was achieved by applying the stapler. The technique was found to
      be feasible. Peritoneal samples, collected after transanal specimen extraction,
      did not demonstrate bacterial growth. Although, this is a novel and evolving
      procedure, its minimally invasive nature, as well as aseptic bowel manipulation
      during endolumenal rectal resection, has the potential to limit the complications
      associated with abdominal wall incision and surgical site infection. 

PMID- 25057142
TI  - Unilateral whisker trimming in newborn rats alters neuronal coincident discharge
      among mature barrel cortex neurons.
AB  - It is known that sensory deprivation, including postnatal whisker trimming, can
      lead to severe deficits in the firing rate properties of cortical neurons. Recent
      results indicate that development of synchronous discharge among cortical neurons
      is also activity influenced, and that correlated discharge is significantly
      impaired following loss of bilateral sensory input in rats. Here we investigate
      whether unilateral whisker trimming (unilateral deprivation or UD) after birth
      interferes in the same way with the development of synchronous discharge in
      cortex. We measured the coincidence of spikes among pairs of neurons recorded
      under urethane anesthesia in one whisker barrel field deprived by trimming all
      contralateral whiskers for 60 days after birth (UD), and in untrimmed controls
      (CON). In the septal columns around barrels, UD significantly increased the
      coincident discharge among cortical neurons compared with CON, most notably in
      layers II/III. In contrast, synchronous discharge was normal between layer IV UD
      barrel neurons: i.e., not different from CON. Thus, while bilateral whisker
      deprivation (BD) produced a global deficit in the development of synchrony in
      layer IV, UD did not block the development of synchrony between neurons in layer
      IV barrels and increased synchrony within septal circuits. We conclude that
      changes in synchronous discharge after UD are unexpectedly different from those
      recorded after BD, and we speculate that this effect may be due to the driven
      activity from active commissural inputs arising from the contralateral hemisphere
      that received normal activity levels during postnatal development.

PMID- 25057143
TI  - Spatiotemporal control of interlimb coordination during transverse split-belt
      locomotion with 1:1 or 2:1 coupling patterns in intact adult cats.
AB  - Interlimb coordination must be flexible to adjust to an ever-changing
      environment. Here adjustments in interlimb coordination were quantified during
      tied-belt (equal speed of the fore- and hindlimbs) and transverse split-belt
      (unequal speed of the fore- and hindlimbs) locomotion in five intact adult cats.
      Cats performed tied-belt locomotion at 0.4 m/s and 0.8 m/s. For transverse split
      belt locomotion, the forelimbs stepped at 0.4 m/s and 0.8 m/s while the hindlimbs
      stepped at 0.8 m/s (4F8H condition) and 0.4 m/s (8F4H condition), respectively.
      In the 8F4H condition, the forelimbs could take two steps within one hindlimb
      cycle, or a 2:1 forelimb-hindlimb relationship. The sequence of limbs contacting
      the ground and the duration of support periods were differentially modified if
      the forelimbs stepped faster or slower than the hindlimbs. During transverse
      split-belt locomotion, the hindlimbs performed longer strides when the forelimbs
      took shorter strides. In the 8F4H condition with a 2:1 forelimb-hindlimb
      relationship, phase and gap intervals for the first and second steps were found
      around certain values and were not randomly distributed, indicating that a new
      coupling pattern was established. However, temporal and spatial coordination
      indexes revealed that bilateral coordination between hindlimbs was less accurate
      and more variable with a 2:1 coupling pattern. Importantly, the animals did not
      stumble, indicating that spatial and temporal adjustments in interlimb
      coordination allowed the animals to maintain dynamic stability. The results
      provide a better understanding of the spatiotemporal adjustments that take place
      among the four limbs during locomotion when interlimb coordination is challenged.

PMID- 25057144
TI  - Shared muscle synergies in human walking and cycling.
AB  - The motor system may rely on a modular organization (muscle synergies activated
      in time) to execute different tasks. We investigated the common control features
      of walking and cycling in healthy humans from the perspective of muscle
      synergies. Three hypotheses were tested: 1) muscle synergies extracted from
      walking trials are similar to those extracted during cycling; 2) muscle synergies
      extracted from one of these motor tasks can be used to mathematically reconstruct
      the electromyographic (EMG) patterns of the other task; 3) muscle synergies of
      cycling can result from merging synergies of walking. A secondary objective was
      to identify the speed (and cadence) at which higher similarities emerged. EMG
      activity from eight muscles of the dominant leg was recorded in eight healthy
      subjects during walking and cycling at four matched cadences. A factorization
      technique [nonnegative matrix factorization (NNMF)] was applied to extract
      individual muscle synergy vectors and the respective activation coefficients
      behind the global muscular activity of each condition. Results corroborated
      hypotheses 2 and 3, showing that 1) four synergies from walking and cycling can
      successfully explain most of the EMG variability of cycling and walking,
      respectively, and 2) two of four synergies from walking appear to merge together
      to reconstruct one individual synergy of cycling, with best reconstruction values
      found for higher speeds. Direct comparison of the muscle synergy vectors of
      walking and the muscle synergy vectors of cycling (hypothesis 1) produced
      moderated values of similarity. This study provides supporting evidence for the
      hypothesis that cycling and walking share common neuromuscular mechanisms.

PMID- 25057145
TI  - Persistence of the dark-background-contingent gaze upshift during visual
      fixations of rhesus monkeys.
AB  - During visual fixations, the eyes are directed so that the image of the target
      (object of interest) falls on the fovea. An exception to this rule was described
      in macaque monkeys (though not in humans): dark background induces a gaze shift
      upwards, sometimes large enough to shift the target's image off the fovea. In
      this article we address an aspect not previously rigorously studied, the time
      course of the upshift. The time course is critical for determining whether the
      upshift is indeed an attribute of visual fixation or, alternatively, of saccades
      that precede the fixation. These alternatives lead to contrasting predictions
      regarding the time course of the upshift (durable if the upshift is an attribute
      of fixation, transient if caused by saccades). We studied visual fixations with
      dark and bright background in three monkeys. We confined ourselves to a single
      upshift-inducing session in each monkey so as not to study changes in the upshift
      caused by training. Already at their first sessions, all monkeys showed clear
      upshift. During the first 0.5 s after the eye reached the vicinity of the target,
      the upshift was on average larger, but also more variable, than later in the
      trial; this initial high value 1) strongly depended on target location and was
      maximal at locations high on the screen, and 2) appears to reflect mostly the
      intervals between the primary and correction saccades. Subsequently, the upshift
      stabilized and remained constant, well above zero, throughout the 2-s fixation
      interval. Thus there is a persistent background-contingent upshift genuinely of
      visual fixation.

PMID- 25057146
TI  - Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in
      hippocampal area CA1 of adult rats and mice.
AB  - Hippocampal long-term potentiation (LTP) is a model system for studying cellular
      mechanisms of learning and memory. Recent interest in mechanisms underlying the
      advantage of spaced over massed learning has prompted investigation into the
      effects of distributed episodes of LTP induction. The amount of LTP induced in
      hippocampal area CA1 by one train (1T) of theta-burst stimulation (TBS) in young
      Sprague-Dawley rats was further enhanced by additional bouts of 1T given at 1-h
      intervals. However, in young Long-Evans (LE) rats, 1T did not initially saturate
      LTP. Instead, a stronger LTP induction paradigm using eight trains of TBS (8T)
      induced saturated LTP in hippocampal slices from both young and adult LE rats as
      well as adult mice. The saturated LTP induced by 8T could be augmented by another
      episode of 8T following an interval of at least 90 min. The success rate across
      animals and slices in augmenting LTP by an additional episode of 8T increased
      significantly with longer intervals between the first and last episodes, ranging
      from 0% at 30- and 60-min intervals to 13-66% at 90- to 180-min intervals to 90
      100% at 240-min intervals. Augmentation above initially saturated LTP was blocked
      by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist D-2-amino-5
      phosphonovaleric acid (D-APV). These findings suggest that the strength of
      induction and interval between episodes of TBS, as well as the strain and age of
      the animal, are important components in the augmentation of LTP.

PMID- 25057147
TI  - Vocal motor changes beyond the sensitive period for song plasticity.
AB  - Behavior is critically shaped during sensitive periods in development. Birdsong
      is a learned vocal behavior that undergoes dramatic plasticity during a sensitive
      period of sensorimotor learning. During this period, juvenile songbirds engage in
      vocal practice to shape their vocalizations into relatively stereotyped songs. By
      the time songbirds reach adulthood, their songs are relatively stable and thought
      to be "crystallized." Recent studies, however, highlight the potential for adult
      song plasticity and suggest that adult song could naturally change over time. As
      such, we investigated the degree to which temporal and spectral features of song
      changed over time in adult Bengalese finches. We observed that the sequencing and
      timing of song syllables became more stereotyped over time. Increases in the
      stereotypy of syllable sequencing were due to the pruning of infrequently
      produced transitions and, to a lesser extent, increases in the prevalence of
      frequently produced transitions. Changes in song tempo were driven by decreases
      in the duration and variability of intersyllable gaps. In contrast to significant
      changes to temporal song features, we found little evidence that the spectral
      structure of adult song syllables changed over time. These data highlight
      differences in the degree to which temporal and spectral features of adult song
      change over time and support evidence for distinct mechanisms underlying the
      control of syllable sequencing, timing, and structure. Furthermore, the observed
      changes to temporal song features are consistent with a Hebbian framework of
      behavioral plasticity and support the notion that adult song should be considered
      a form of vocal practice. 

PMID- 25057148
TI  - Spectral receptive fields do not explain tuning for boundary curvature in V4.
AB  - The midlevel visual cortical area V4 in the primate is thought to be critical for
      the neural representation of visual shape. Several studies agree that V4 neurons
      respond to contour features, e.g., convexities and concavities along a shape
      boundary, that are more complex than the oriented segments encoded by neurons in
      the primary visual cortex. Here we compare two distinct approaches to modeling V4
      shape selectivity: one based on a spectral receptive field (SRF) map in the
      orientation and spatial frequency domain and the other based on a map in an
      object-centered angular position and contour curvature space. We test the ability
      of these two characterizations to account for the responses of V4 neurons to a
      set of parametrically designed two-dimensional shapes recorded previously in the
      awake macaque. We report two lines of evidence suggesting that the SRF model does
      not capture the contour sensitivity of V4 neurons. First, the SRF model discards
      spatial phase information, which is inconsistent with the neuronal data. Second,
      the amount of variance explained by the SRF model was significantly less than
      that explained by the contour curvature model. Notably, cells best fit by the
      curvature model were poorly fit by the SRF model, the latter being appropriate
      for a subset of V4 neurons that appear to be orientation tuned. These limitations
      of the SRF model suggest that a full understanding of midlevel shape
      representation requires more complicated models that preserve phase information
      and perhaps deal with object segmentation. 

PMID- 25057149
TI  - Ecological consequences of plant clonality.

PMID- 25057151
TI  - Dietary patterns and mortality in a Chinese population.
AB  - BACKGROUND: Limited research has examined the association between dietary
      patterns and mortality, especially in non-Western populations. OBJECTIVE: We
      examined the association of dietary patterns with all-cause mortality and cause
      specific mortality in the Singapore Chinese Health Study, which included a unique
      ethnic population with strong Western and South Asian cultural influences.
      DESIGN: We conducted a prospective data analysis of the Singapore Chinese Health
      Study, which included 52,584 Chinese men and women (aged 45-74 y) who were free
      of diabetes, cardiovascular disease (CVD), and cancer at baseline (1993-1998) and
      followed through 2011 with 10,029 deaths. The following 2 major dietary patterns
      were identified by using a principal components analysis: a vegetable-, fruit-,
      and soy-rich (VFS) pattern and a dim sum- and meat-rich (DSM) dietary pattern.
      Pattern scores for each participant were calculated and examined with all-cause
      and cause-specific mortality risks by using a Cox proportional hazards
      regression. RESULTS: The VFS pattern was inversely associated with all-cause
      mortality and each cause-specific category (CVD, cancer, and respiratory) of
      mortality during the follow-up period. Compared with the lowest quintile of the
      VFS pattern, HRs for quintiles 2-5 for all-cause mortality were 0.90, 0.79, 0.80,
      and 0.75, respectively (P-trend < 0.0001). The DSM pattern was positively
      associated with CVD mortality in the whole population (HR for fifth quintile
      compared with first quintile: 1.23; 95% CI: 1.07, 1.40; P-trend = 0.001).
      Positive associations between the DSM pattern and cancer and all-cause mortality
      were only present in ever-smokers. In ever-smokers, relative to the first
      quintile, HRs for quintiles 2-5 of the DSM pattern for all-cause mortality were
      1.04, 1.04, 1.13, and 1.24, respectively (P-trend < 0.0001). Similarly, HRs for
      quintiles 2-5 for cancer mortality were 1.08, 1.03, 1.25, and 1.34, respectively
      (P-trend < 0.0001). The DSM pattern was not associated with respiratory
      mortality. CONCLUSION: Dietary patterns are strongly associated with mortality in
      Chinese Singaporeans.

PMID- 25057152
TI  - Mandatory trans fat labeling regulations and nationwide product reformulations to
      reduce trans fatty acid content in foods contributed to lowered concentrations of
      trans fat in Canadian women's breast milk samples collected in 2009-2011.
AB  - BACKGROUND: Recent efforts in Canada to reduce industrial trans fatty acids
      (TFAs) in foods include mandated inclusion of TFA content on food labels and
      recommendations by Health Canada that encourage the food industry to voluntarily
      limit TFA content in all vegetable oils and soft margarines and in all other
      prepackaged foods to <2% and <5% of total fat, respectively. OBJECTIVE: To assess
      the impact of these efforts, we measured the concentration of TFAs in human
      breast milk samples. DESIGN: The TFA content in 639 breast milk samples collected
      in 2009, 2010, and 2011 from breastfeeding mothers in 10 major cities across
      Canada was analyzed by gas chromatography. RESULTS: The mean (+/-SD) TFA contents
      were 2.7 +/- 0.9% (n = 153, range: 1.4-7.2%), 2.2 +/- 0.7% (n = 309, range: 1.0
      6.8%), and 1.9 +/- 0.5% (n = 177, range: 0.9-3.4%) of total milk fat for samples
      collected in 2009, 2010, and 2011, respectively. These values are considerably
      lower than the value of 7.2 +/- 3.0% (range: 0.1-17.2%) found previously for
      Canadian human milk in 1992. On the basis of a linear correlation between the
      percentage of TFAs in the diet and human milk fat established by Craig-Schmidt et
      al, and assuming that 30% of energy of a lactating mother's diet is derived from
      fat, we estimated from the TFA human milk fat data that TFA intake of Canadian
      breastfeeding mothers was 0.9%, 0.5%, and 0.3% of total energy in 2009, 2010, and
      2011, respectively. These estimated values are lower than the WHO's maximum
      recommended intake of 1% of total energy for a healthy diet. CONCLUSIONS: The
      results suggest that the trans fat labeling regulations introduced in 2003 and
      recommendations by Health Canada in 2007 instructing the food manufacturers and
      restaurants to limit TFAs in foods have resulted in significant reductions in
      TFAs in the diets of Canadian breastfeeding mothers and their breast milk.

PMID- 25057153
TI  - An objective estimate of energy intake during weight gain using the intake
      balance method.
AB  - BACKGROUND: Estimates of energy intake (EI) in humans have limited validity.
      OBJECTIVE: The objective was to test the accuracy and precision of the intake
      balance method to estimate EI during weight gain induced by overfeeding. DESIGN:
      In 2 studies of controlled overfeeding (1 inpatient study and 1 outpatient
      study), baseline energy requirements were determined by a doubly labeled water
      study and caloric titration to weight maintenance. Overfeeding was prescribed as
      140% of baseline energy requirements for 56 d. Changes in weight, fat mass (FM),
      and fat-free mass (FFM) were used to estimate change in energy stores (DeltaES).
      Overfeeding EI was estimated as the sum of baseline energy requirements, thermic
      effect of food, and DeltaES. The estimated overfeeding EI was then compared with
      the actual EI consumed in the metabolic chamber during the last week of
      overfeeding. RESULTS: In inpatient individuals, calculated EI during overfeeding
      determined from DeltaES in FM and FFM was (mean +/- SD) 3461 +/- 848 kcal/d,
      which was not significantly (-29 +/- 273 kcal/d or 0.8%; limits of agreement: 
      564, 505 kcal/d; P = 0.78) different from the actual EI provided (3490 +/- 729
      kcal/d). Estimated EI determined from DeltaES in weight closely estimated actual
      intake (-7 +/- 193 kcal/d or 0.2%; limits of agreement: -386, 370 kcal/d; P =
      0.9). In free-living individuals, estimated EI during overfeeding determined from
      DeltaES in FM and FFM was 4123 +/- 500 kcal/d and underestimated actual EI (4286
      +/- 488 kcal/d; -162 +/- 301 kcal or 3.8%; limits of agreement: -751, 427 kcal/d;
      P = 0.003). Estimated EI determined from DeltaES in weight also underestimated
      actual intake (-159 +/- 270 kcal/d or 3.7%; limits of agreement: -688, 370
      kcal/d; P = 0.001). CONCLUSION: The intake-balance method can be used to estimate
      EI during a period of weight gain as a result of 40% overfeeding in individuals
      who are inpatients or free-living with only a slight underestimate of actual EI
      by 0.2-3.8%.

PMID- 25057154
TI  - Evaluation of various biomarkers as potential mediators of the association
      between coffee consumption and incident type 2 diabetes in the EPIC-Potsdam
      Study.
AB  - BACKGROUND: The inverse association between coffee consumption and the risk of
      type 2 diabetes (T2D) is well established; however, little is known about
      potential mediators of this association. OBJECTIVE: We aimed to investigate the
      association between coffee consumption and diabetes-related biomarkers and their
      potential role as mediators of the association between coffee consumption and
      T2D. DESIGN: We analyzed a case-cohort study (subcohort: n = 1610; verified
      incident T2D cases: n = 417) nested within the European Prospective Investigation
      into Cancer and Nutrition-Potsdam study involving 27,548 middle-aged
      participants. Habitual coffee consumption was assessed with a validated,
      semiquantitative food-frequency questionnaire. We evaluated the association
      between coffee consumption and several T2D-related biomarkers, such as liver
      markers (reflected by gamma-glutamyltransferase, fetuin-A, and sex hormone
      binding globulin), markers of dyslipidemia (high-density lipoprotein cholesterol
      and triglycerides), inflammation [C-reactive protein (CRP)], an adipokine
      (adiponectin), and metabolites, stratified by sex. RESULTS: Coffee consumption
      was inversely associated with diacyl-phosphatidylcholine C32:1 in both sexes and
      with phenylalanine in men, as well as positively associated with acyl-alkyl
      phosphatidylcholines C34:3, C40:6, and C42:5 in women. Furthermore, coffee
      consumption was inversely associated with fetuin-A (P-trend = 0.06) and CRP in
      women and gamma-glutamyltransferase and triglycerides in men. Coffee consumption
      tended to be inversely associated with T2D risk in both sexes, reaching
      significance only in men [HR (95% CI): women: >=4 compared with >0 to <2 cups
      coffee/d: 0.78 (0.46, 1.33); men: >=5 compared with >0 to <2 cups coffee/d: 0.40
      (0.19, 0.81)]. The association between coffee consumption and T2D risk in men was
      slightly reduced after adjustment for phenylalanine or lipid markers.
      CONCLUSIONS: Coffee consumption was inversely associated with a diacyl
      phosphatidylcholine and liver markers in both sexes and positively associated
      with certain acyl-alkyl-phosphatidylcholines in women. Furthermore, coffee
      consumption showed an inverse trend with CRP in women and with triglycerides and
      phenylalanine in men. However, these markers explained only to a small extent the
      inverse association between long-term coffee consumption and T2D risk.

PMID- 25057155
TI  - Circulating non-transferrin-bound iron after oral administration of supplemental
      and fortification doses of iron to healthy women: a randomized study.
AB  - BACKGROUND: After the oral administration of iron, the production of circulating
      non-transferrin-bound iron may contribute to an increased risk of illness in
      malaria-endemic areas that lack effective medical services. OBJECTIVE: In healthy
      women with a range of body iron stores, we aimed to determine effects on the
      production of circulating non-transferrin-bound iron resulting from the oral
      administration of 1) a supplemental dose of iron (60 mg) with water, 2) a
      supplemental dose of iron (60 mg) with a standard test meal, and 3) a
      fortification dose of iron (6 mg) with a standard test meal. DESIGN: With the use
      of serum ferritin as the indicator, healthy women with replete iron stores
      (ferritin concentration >25 MUg/L; n = 16) and reduced iron stores (ferritin
      concentration <=25 MUg/L; n = 16) were enrolled in a prospective, randomized,
      crossover study. After the oral administration of aqueous solutions of ferrous
      sulfate isotopically labeled with 54Fe, 57Fe, or 58Fe, blood samples were
      collected for 8 h, and iron absorption was estimated by erythrocyte incorporation
      at 14 d. RESULTS: At 4 h, serum non-transferrin-bound iron reached peaks with
      geometric mean (95% CI) concentrations of 0.81 MUmol/L (0.56, 1.1 MUmol/L) for 60
      mg Fe with water and 0.26 MUmol/L (0.15, 0.38 MUmol/L) for 60 mg Fe with food but
      was at assay limits of detection (0.1 MUmol Fe/L) for 6 mg Fe with food. For the
      60 mg Fe without food, the area under the curve over 8 h for serum non
      transferrin-bound iron was positively correlated with the amount of iron absorbed
      (R = 0.49, P < 0.01) and negatively correlated with serum ferritin (R = -0.39, P
      < 0.05). CONCLUSIONS: In healthy women, the production of circulating non
      transferrin-bound iron is determined by the rate and amount of iron absorbed. The
      highest concentrations of non-transferrin-bound iron resulted from the
      administration of supplemental doses of iron without food. Little or no
      circulating non-transferrin-bound iron resulted from the consumption of a meal
      with a fortification dose of iron.

PMID- 25057156
TI  - Cardiovascular disease and vitamin D supplementation: trial analysis, systematic
      review, and meta-analysis.
AB  - BACKGROUND: Low 25-hydroxyvitamin D status has been associated with increased
      cardiovascular events in epidemiologic studies. OBJECTIVE: We assessed whether
      vitamin D supplementation reduces cardiac failure, myocardial infarction (MI),
      and stroke through an analysis of the Randomised Evaluation of Calcium Or vitamin
      D (RECORD) randomized controlled trial (RCT), a systematic review, and a meta
      analysis. DESIGN: Two analyses were undertaken. The first analysis was a trial
      analysis. The RECORD was a factorial RCT that compared vitamin D3 (800 IU/d),
      calcium (1000 mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events
      were collected throughout the trial and 3-y posttrial follow-up. Data were
      analyzed by using Cox regression. The second analysis was a systematic review.
      MEDLINE, EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched
      for RCTs that evaluated vitamin D from 1980 to 2013. RCTs with >=1 y of follow-up
      and participants mean or median age >=60 y were included. Meta-analyses were
      based on a Bayesian fixed-effects model by using a complementary log-log link
      function to account for varying lengths of follow-up. RESULTS: In the trial
      analysis, we showed that, for the 5292 participants in the RECORD trial, HRs (95%
      CIs) for vitamin D compared with no vitamin D for cardiac failure, MI, and stroke
      were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8, 1.32), respectively.
      Twenty-one studies met the inclusion criteria for the systematic review (n =
      13,033). Estimated HRs (credible intervals) for vitamin D compared with the
      placebo or control for on-study events for cardiac failure, MI, and stroke were
      0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29), respectively.
      CONCLUSION: Vitamin D supplementation might protect against cardiac failure in
      older people but does not appear to protect against MI or stroke.

PMID- 25057158
TI  - Postprandial lower limb pain: An unusual presentation of visceral arteries
      occlusion.
AB  - This case report describes an atypical and unique presentation of mesenteric
      arteries occlusive disease. The patient presented with typical symptoms of
      chronic mesenteric ischemia, as well as with an atypical new symptom;
      postprandial buttock and lower limbs pain. Pain followed the time curve of the
      postprandial abdominal discomfort, starting 30 min after meals and gradually
      resolving within 2 h. The patient had been tolerating the signs of chronic
      mesenteric ischemia quite well by adjusting the quantity of food per meal to
      relieve symptoms. Angiography showed that the celiac artery, the superior
      mesenteric artery, and distal aorta were occluded, leaving the inferior
      mesenteric artery as the only feeding vessel of all abdominal viscera and both
      the lower limbs. Since an English medical literature search returned only one
      marginally similar case, we consider this case of iliac arteries' "steal
      syndrome" from the inferior mesenteric artery unique.

PMID- 25057157
TI  - Association of self-reported sleep duration with eating behaviors of American
      adults: NHANES 2005-2010.
AB  - BACKGROUND: Published evidence suggests an inverse association between sleep
      duration and body weight status. OBJECTIVE: We examined the association of sleep
      duration with eating behaviors reported by adult Americans to understand the
      relation between sleep duration and body weight status. DESIGN: This cross
      sectional study used sleep duration and dietary data from the continuous NHANES
      conducted from 2005 to 2010 (n = 15,199, age >=20 y). Eating behaviors examined
      included the following: reporting of and energy from main meals (breakfast,
      lunch, and dinner) and snacks (before breakfast, after dinner, and after 2000 h),
      intermeal intervals, time of day of main meal reporting, and intakes of
      macronutrients and beverages. Multiple regression methods were used to examine
      the independent association of hours of sleep duration grouped as short (<=6 h),
      average (7-8 h), and long (>=9 h) with eating behavior outcomes. RESULTS:
      Relative to average-duration sleepers, a smaller percentage of short-duration
      sleepers mentioned breakfast, lunch (women only), and dinner in the recall (P <=
      0.04). They also reported a lower mean percentage of energy from main meals but
      higher energy from all snacks (P <= 0.0004) and after 2000 h (P = 0.03). Short
      duration sleepers reported the earliest eating time of the first episode and the
      latest time of the last eating episode. Absolute amounts of sugar and caffeine
      and percentage of energy from beverages (women only) were higher in short
      duration sleepers. However, the total number of eating episodes and energy intake
      were not related with sleep duration. CONCLUSIONS: Short-duration sleepers began
      eating earlier and ended their eating later in the day, but despite the longer
      eating period, they did not report more eating events. Profiles of the relative
      contribution of main meals and snacks, at or after 2000 h eating, and beverages
      in short-duration sleepers were suggestive of eating behaviors that may increase
      energy intake, but 24-h energy intake did not differ among categories of sleep
      duration.

PMID- 25057159
TI  - Genetic etiology of coronary artery disease considering NOS 3 gene variant
      rs1799983.
AB  - Reduced production of nitric oxide due to rs1799983 single nucleotide
      polymorphism in nitric oxide synthase 3 gene (NOS3) may enhance the risk of
      coronary artery disease. The association of rs1799983 polymorphism with coronary
      artery disease was investigated in the local population of Pakistan. Study
      consisted of 376 individuals, out of which 198 were coronary artery disease
      patients and 178 were normal healthy individuals. Allele-specific polymerase
      chain reaction (PCR) based strategy was used for the detection of different
      genotypes of rs1799983 polymorphism. PCR amplification results were obtained for
      354 samples. Frequency of T allele was higher as compared to G allele in our
      population. Strong association between rs1799983 and coronary artery disease was
      observed (p < 0.01). TT genotype was found to enhance 5.717 times the risk of
      coronary artery disease (odds ratio (OR): 5.717; 95% confidence interval (95% CI)
      3.586-9.115). On the basis of present results, it can be concluded that rs1799983
      is strongly associated with coronary artery disease in our population and TT
      genotype of this polymorphism enhanced the risk of coronary artery disease in
      Pakistani population.

PMID- 25057160
TI  - Production of a monoclonal antibody against serum immunoglobulin M of South
      American camelids and assessment of its suitability in two immunoassays.
AB  - A monoclonal antibody (mAb) was produced against immunoglobulin M (IgM) of South
      American camelids. A single radial immunodiffusion (SRID) assay and a competitive
      enzyme-linked immunosorbent assay (ELISA) were developed to measure IgM in serum
      samples. Isotype and specificity of the mAb were assessed. The performance of the
      SRID assay was preliminarily evaluated in terms of working range, plate stability
      over a 4-week period, and initial intra- and interassay variation. The
      concentration of IgM was determined in 55 samples by SRID assay and ELISA, and
      results were not significantly different by t-test (0.64 +/- 0.19 mg/ml for the
      SRID assay, and 0.58 +/- 0.24 mg/ml for ELISA; P = 0.1489). The mAb was shown to
      be stable over the 4-week evaluation period, and the SRID assay was reproducible
      when tested in triplicate for intra-assay variability and in quadruplicate for
      interassay variability, with a percentage coefficient of variation of less than
      or equal to 5%. Also, the SRID assay proved to be sensitive enough to measure IgM
      levels in undiluted serum samples, and had a good correlation with ELISA. The
      current study is intended to submit a preliminary report of a mAb against IgM of
      South American camelids, and suggest the future potential of the mAb developed
      for diagnostic application, including use in the SRID assay. 

PMID- 25057161
TI  - Reference intervals for acute phase protein and serum protein electrophoresis
      values in captive Asian elephants (Elephas maximus).
AB  - Acute phase protein (APP) immunoassays and serum protein electrophoresis (SPEP)
      are assays for evaluating the inflammatory response and have use as diagnostic
      tools in a variety of species. Acute phase proteins are markers of inflammation
      that are highly conserved across different species while SPEP separates and
      quantifies serum protein fractions based on their physical properties. In the
      current study, serum samples from 35 clinically healthy Asian elephants (Elephas
      maximus) were analyzed using automated assays for C-reactive protein, serum
      amyloid A, and haptoglobin and SPEP. Robust methods were used to generate
      reference intervals for the APPs: C-reactive protein (1.3-12.8 mg/l), serum
      amyloid A (0-47.5 mg/l), and haptoglobin (0-1.10 mg/ml). In addition, SPEP was
      performed on these samples to establish reference intervals for each protein
      fraction. A combination of APPs and SPEP measurements are valuable adjunctive
      diagnostic tools in elephant health care. 

PMID- 25057162
TI  - Presumed primary intraocular chondrosarcoma in cats.
AB  - Following unilateral enucleation, 4 Domestic Shorthair cats with an average age
      of 12.5 years (range: 9-16 years) were histologically diagnosed with a presumed
      primary intraocular chondrosarcoma at the Comparative Ocular Pathology Laboratory
      of Wisconsin (Madison, Wisconsin). Medical records and follow-up were available
      for 3 of the 4 cats. Clinically, only 1 eye was affected in each cat; a mass
      lesion was noted in 2 cats, and a neoplasm was suspected in the other 2 cats.
      Grossly, 3 tumors presented as coalescing, poorly demarcated, white, friable
      masses filling the vitreous and intraocular chambers; 1 tumor presented as a
      solitary, well-demarcated, tan mass involving the iris and ciliary body.
      Histologically, all 4 neoplasms were composed of haphazardly arranged plump
      neoplastic spindle cells surrounded by irregular islands and thick trabeculae of
      abundant, variably basophilic, and Alcian blue-positive chondromatous matrix.
      None of the cats presented histologically or clinically with signs suggestive of
      feline posttraumatic ocular sarcoma. Two cats are still alive and healthy 6
      months and 3 years following enucleation. One cat died 6 months following
      enucleation; however, this cat suffered from poorly controlled diabetes mellitus,
      and the cause of death is undetermined. No other tumors or skeletal lesions were
      identified that could suggest a metastatic tumor to the eye. The origin of
      primary intraocular chondrosarcoma is unclear, but is presumed to be ocular
      multipotent mesenchymal stem cells. Four cases of intraocular chondrosarcoma in
      cats not associated with the posttraumatic sarcoma complex of intraocular tumors
      are described. 

PMID- 25057163
TI  - Suppurative otitis and ascending meningoencephalitis associated with Bacteroides
      tectus and Porphyromonas gulae in a captive Parma wallaby (Macropus parma) with
      toxoplasmosis.
AB  - A 6-year-old female Parma wallaby (Macropus parma) at a zoo in California
      developed acute ataxia and left-sided circling. Despite intensive care, clinical
      signs progressed to incoordination and prostration, and the animal was
      euthanized. At necropsy, the left tympanic cavity was filled with homogeneous
      suppurative exudate that extended into the cranium expanding the meninges and
      neuroparenchyma in the lateral and ventral aspect of the caudal ipsilateral
      brainstem and medulla oblongata. Microscopically, the brainstem showed regional
      severe suppurative meningoencephalitis with large numbers of neutrophils, fewer
      macrophages, and lymphocytes admixed with fibrin, necrotic cellular debris,
      hemorrhage, and mineralization, with numerous intralesional Gram-negative
      bacilli. Bacteroides spp. and Porphyromonas spp. were isolated on anaerobic
      culture from the meninges, and the bacteria were further characterized by partial
      16S ribosomal RNA gene sequencing as Bacteroides tectus and Porphyromonas gulae.
      Bacterial aerobic culture from the meninges yielded very low numbers of mixed
      flora and Proteus spp., which were considered contaminants. Culture of Mycoplasma
      spp. from middle ear and meninges was negative. Additionally, Toxoplasma gondii
      cysts were detected by immunohistochemistry in the heart and brain, and anti
      Toxoplasma antibodies were detected in serum. The genera Bacteroides and
      Porphyromonas have been associated with oral disease in marsupials; but not with
      otitis and meningoencephalitis. The results of the present work highlight the
      importance of performing anaerobic cultures in the diagnostic investigation of
      cases of suppurative otitis and meningoencephalitis in macropods. 

PMID- 25057165
TI  - The current and future impact of human papillomavirus on treatment of squamous
      cell carcinoma of the head and neck.
AB  - BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) was
      traditionally associated with smoking and alcohol use; however, human
      papillomavirus (HPV) infection has recently been implicated as a novel risk
      factor for oropharyngeal tumors. Furthermore, HPV-associated oropharyngeal
      carcinoma (OPC) appears to be a distinct entity with different epidemiology,
      biology, and clinical outcomes. METHODS: Here, we comprehensively review the
      existing data regarding HPV status and prognostic or predictive outcomes in both
      the locoregionally advanced (LA) and recurrent/metastatic (RM) disease setting
      and discuss ongoing trials that may eventually impact the treatment of patients
      with HPV-positive (HPV+) SCCHN. RESULTS: A body of retrospective and prospective
      data established an association between HPV+ OPC and better survival,
      particularly for LA disease. Current data on RM disease are limited, but they
      also suggest prognostic significance for HPV. CONCLUSIONS: Better outcomes in
      HPV+ LA disease may allow for less aggressive treatment in the future, and
      several trials are evaluating deintensified regimens in patients with HPV+, LA
      OPC; it should be emphasized that deintensification strategies are appropriate
      only in a clinical research setting and only for selected subgroups of HPV+
      patients. In addition, HPV-targeted strategies, such as vaccines, are currently
      undergoing clinical evaluation. On the other hand, the prognostic impact of HPV
      in RM disease requires further validation before any modifications in treatment
      can be made. Likewise, the predictive significance of HPV status in both disease
      settings remains to be defined. CLINICAL TRIAL NUMBERS: NCT00226239, NCT00301028,
      NCT00387127, NCT00410826, NCT00503997, NCT00514943, NCT00544414, NCT00768664,
      NCT00939627, NCT01084083, NCT01302834, NCT01687413, NCT01706939.

PMID- 25057164
TI  - Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from
      the International Pancreatic Cancer Case-Control Consortium.
AB  - BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of
      pancreatic cancer, but the magnitude of the risk and the time-risk relationship
      are unclear, and there is limited information on the role of antidiabetic
      medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case
      control studies within the Pancreatic Cancer Case-Control Consortium, including
      8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from
      multiple logistic regression models, adjusted for relevant covariates. RESULTS:
      Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes
      2 or more years before cancer diagnosis (or interview, for controls),
      corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09).
      Consistent risk estimates were observed across strata of selected covariates,
      including body mass index and tobacco smoking. Pancreatic cancer risk decreased
      with duration of diabetes, but a significant excess risk was still evident 20 or
      more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics,
      long duration of oral antidiabetic use was associated with a decreased pancreatic
      cancer risk (OR 0.31, 95% CI 0.14-0.69, for >=15 years). Conversely, insulin use
      was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI
      3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI
      0.53-1.70, for >=15 years). CONCLUSION: This study provides the most definitive
      quantification to date of an excess risk of pancreatic cancer among diabetics. It
      also shows that a 30% excess risk persists for more than two decades after
      diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic
      cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas
      insulin showed an inconsistent duration-risk relationship.

PMID- 25057166
TI  - Distal and proximal colon cancers differ in terms of molecular, pathological, and
      clinical features.
AB  - BACKGROUND: Differences exist between the proximal and distal colon in terms of
      developmental origin, exposure to patterning genes, environmental mutagens, and
      gut flora. Little is known on how these differences may affect mechanisms of
      tumorigenesis, side-specific therapy response or prognosis. We explored
      systematic differences in pathway activation and their clinical implications.
      MATERIALS AND METHODS: Detailed clinicopathological data for 3045 colon carcinoma
      patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for
      analysis. A subset of 1404 samples had molecular data, including gene expression
      and DNA copy number profiles for 589 and 199 samples, respectively. In addition,
      413 colon adenocarcinoma from TCGA collection were also analyzed. Tumor side
      effect on anti-epidermal growth factor receptor (EGFR) therapy was assessed in a
      cohort of 325 metastatic patients. Outcome variables considered were relapse-free
      survival and survival after relapse (SAR). RESULTS: Proximal carcinomas were more
      often mucinous, microsatellite instable (MSI)-high, mutated in key tumorigenic
      pathways, expressed a B-Raf proto-oncogene, serine/threonine kinase (BRAF)-like
      and a serrated pathway signature, regardless of histological type. Distal
      carcinomas were more often chromosome instable and EGFR or human epidermal growth
      factor receptor 2 (HER2) amplified, and more frequently overexpressed epiregulin.
      While risk of relapse was not different per side, SAR was much poorer for
      proximal than for distal stage III carcinomas in a multivariable model including
      BRAF mutation status [N = 285; HR 1.95, 95% CI (1.6-2.4), P < 0.001]. Only
      patients with metastases from a distal carcinoma responded to anti-EGFR therapy,
      in line with the predictions of our pathway enrichment analysis. CONCLUSIONS:
      Colorectal carcinoma side is associated with differences in key molecular
      features, some immediately druggable, with important prognostic effects which are
      maintained in metastatic lesions. Although within side significant molecular
      heterogeneity remains, our findings justify stratification of patients by side
      for retrospective and prospective analyses of drug efficacy and prognosis.

PMID- 25057167
TI  - On demand Gamma-Knife strategy can be safely combined with BRAF inhibitors for
      the treatment of melanoma brain metastases.
AB  - BACKGROUND: Both Gamma-Knife radiosurgery (GKRS) and BRAF inhibitors (BRAF-I)
      have been shown to be useful in melanoma patients with brain metastases (BMs),
      thus suggesting that it could be interesting to combine their respective
      advantages. However, cases of radiosensitization following conventional radiation
      therapy in BRAF-I treated patients have raised serious concerns about the real
      feasibility and risk/benefit ratio of this combination. PATIENTS AND METHODS:
      Review by two independent observers of brain magnetic resonance imaging (MRI)
      follow-up pictures, and volume and edema quantifications, and survival assessment
      in all patients who had been treated by GKRS and BRAF-I at a single institution.
      RESULTS: Among 53 GKRS carried out in 30 patients who ever received BRAF-I and
      GKRS, 33 GKRS were carried out in 24 patients while under BRAF-I treatment, from
      which only 4 with an interruption of BRAF-I. The 20 other GKRS were carried out
      in 15 patients (including 9 of the 24) before initiation of BRAF-I treatment. No
      case of radiation-induced necrosis and no scalp radiation dermatitis occurred. A
      >20% increase in volume was observed in 35 of the 263 BM treated by GKRS (13.3%),
      but only 3 clear-cut edemas and 3 hemorrhages were detected within 2 months after
      GKRS, and 4 edemas and 7 hemorrhages later. Neither the MRI features nor the
      incidence of the volume changes, hemorrhage and edema were deemed unexpected for
      melanoma BM treated by GKRS. Median survival from first GKRS under BRAF-I and
      first dose of BRAF-I were 24.8 and 48.8 weeks, respectively. CONCLUSION: This
      series does not show immediate radiotoxicity nor radiation recall, in melanoma
      patients with BRAF-I whose BMs are treated by GKRS. Interrupting BRAF-I for
      stereotactic radiosurgery (SRS) of BM seems useless, although it is still advised
      for other radiation therapies. The potential benefit of combining SRS and BRAF-I
      can be safely tested.

PMID- 25057168
TI  - Evaluating surrogacy metrics and investigating approval decisions of progression
      free survival (PFS) in metastatic renal cell cancer: a systematic review.
AB  - BACKGROUND: In metastatic renal cell cancer (mRCC) trials, progression-free
      survival (PFS) is increasingly used instead of overall survival (OS) as the
      approval end point. Unlike other solid tumors, there is no published
      demonstration of what PFS is needed across and by treatment class in mRCC. We
      determine this and evaluate drug approval decisions in mRCC targeted therapy.
      METHODS: We identified all randomized, controlled trials reporting PFS and OS in
      mRCC. Surrogacy metrics were the coefficient of determination and surrogate
      threshold effect (STE)-the PFS difference needed to predict, with 95% confidence,
      an OS difference. Data from regulatory commentaries, briefing documents and
      transcripts were extracted. RESULTS: No exclusively chemotherapy trial met
      criteria. Of 30 qualifying trials, 11 trials (13 comparisons) used targeted
      therapy. The all-trials and immunotherapy-only trials analysis failed to
      demonstrate a STE. The targeted trials, using the more conservative regression
      analysis demonstrated an STE of 3.9 months and an R(2) of 0.44. Crossover upon
      progression, control to active treatment, was common. Regulatory approval,
      accelerated or regular, labeling, interim analyses, and adjudication were context
      specific. CONCLUSIONS: A new targeted therapy trial showing a PFS difference of
      3.9 months can claim an OS benefit in mRCC. PFS surrogacy for OS in metastatic
      renal cell is not generalizable across all drug classes.

PMID- 25057169
TI  - Erlotinib treatment of meningeal carcinomatosis in lung cancer: more is better.

PMID- 25057170
TI  - Reply to the letter to the editor 'treating breast cancer with trabectedin: a new
      arsenal' by L. Malik.

PMID- 25057171
TI  - Detection of circulating tumor cells for prediction of recurrence after adjuvant
      chemoradiation in locally advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The prognostic role of persistence of circulating tumor cells (CTC)
      after upfront tumor surgery for outcome of adjuvant (chemo)radiation in locally
      advanced squamous cell carcinoma of the head and neck (LASCCHN) was evaluated.
      PATIENTS AND METHODS: In this prospective study, peripheral blood samples from
      144 patients with LASCCHN presenting after tumor resection for adjuvant treatment
      were analyzed for CTC. Their detection was correlated with tumor site, clinical
      risk factors, disease-free (DFS) and overall survival (OS). RESULTS: CTC were
      detected in 42 of 144 patients (29%). CTC detection was higher in cases with
      nodal involvement and in carcinomas located at the tonsil or base of tongue but
      was not influenced by age, smoking history, T stage, extracapsular lymph node
      extension, surgical margins or the human papillomavirus status. Overall, the
      presence of CTC was not predictive for OS or DFS. However, while in oropharyngeal
      carcinomas (OPC, n = 63), the detection of CTC was associated per trend with
      improved DFS [CTC+ versus CTC- (% of patients without evidence of disease at 2
      years): 100% versus 79%; log rank: P = 0.059]; the reverse was observed for
      carcinomas from other sites (non-OPC, n = 81; CTC+ versus CTC-: 29% versus 75%; P
      = 0.001). In multivariate analysis, CTC remained an independent prognostic marker
      for DFS [hazard ratio (HR) 4.3, 95% confidence interval (CI) 1.7-10.9, P = 0.002]
      and OS (HR 2.7, 95% CI 1.2-6.3, P = 0.016) in non-OPC. CONCLUSIONS: Assessment of
      CTC in non-OPC should prove useful for identification of patients who benefit
      from treatment intensification. The basis for the good prognostic value of CTC in
      OPC has to be elucidated in future studies.

PMID- 25057172
TI  - Low albumin-to-globulin ratio associated with cancer incidence and mortality in
      generally healthy adults.
AB  - BACKGROUND: Chronic inflammation is known to be one of the main steps in
      carcinogenesis. Identification of those with chronic inflammation may help
      identify subjects at risk of cancer. Previous studies have reported low albumin
      to-globulin ratio (AGR) to be associated with increased cancer mortality in
      cancer patients, but there has been no study based on healthy populations.
      PATIENTS AND METHODS: Our retrospective cohort study involved 26 974 generally
      healthy adults aged 30 or older who visited Seoul National University Hospital
      Health Promotion Center for self-referred health checkup. National medical
      service claims data were used to determine cancer incidence, and Korean death
      registry data was used to determine mortality. Median follow-up time for survival
      was 5.9 years (interquartile range 4.1 years). RESULTS: Compared with subjects
      with AGR >= 1.5, subjects with 1.1 > AGR >= 1.0 and 1.0 > AGR showed adjusted
      hazard ratio (aHR) 2.69 (95% confidence interval, CI, 1.54-4.72) and aHR 6.71
      (95% CI 3.56-12.66) for all-cause mortality, aHR 2.95 (95% CI 1.42-6.11) and aHR
      4.38 (95% CI 1.57-12.25) for cancer mortality, and aHR 2.07 (95% CI 1.28-3.36)
      and aHR 3.99 (95% CI 2.10-7.58) for cancer incidence, respectively. When cancer
      incidence events after 2 years from baseline were separately analyzed, subjects
      with 1.1 > AGR >= 1.0 and 1.0 > AGR were associated with aHR 1.88 (95% CI 1.01
      3.48) and aHR 2.55 (95% CI 1.03-7.11) for cancer incidence, respectively. Cancer
      events were increased in all types of cancer, but especially in liver and
      hematologic malignancies. CONCLUSIONS: Low AGR is a risk factor for cancer
      incidence and mortality, both short- and long terms, in a generally healthy
      screened population. The results of this study need to be replicated in larger
      studies, along with the determination of the sensitivity and other diagnostic
      values of low AGR.

PMID- 25057173
TI  - EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in
      a randomized phase III study of second-line treatment of patients with advanced
      non-small cell lung cancer.
AB  - BACKGROUND: ZODIAC was a randomized phase III study of second-line treatment in
      patients with advanced non-small cell lung cancer (NSCLC) that evaluated the
      addition of vandetanib to docetaxel. The study showed a statistically significant
      improvement in progression-free survival and objective response rate, but not in
      overall survival for unselected patients. This study evaluated epidermal growth
      factor receptor (EGFR) gene mutation, copy number gain, and protein expression,
      and KRAS gene mutation, in pretreatment tumor samples as potential biomarkers
      predicting benefit from vandetanib as second-line treatment of NSCLC. PATIENTS
      AND METHODS: After progression following first-line chemotherapy, 1391 patients
      with locally advanced or metastatic (stage IIIB/IV) NSCLC were randomized 1 : 1
      to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m(2) every 21 days) or
      placebo plus docetaxel in the ZODIAC study. Archival tumor samples (n = 570) were
      collected from consenting patients (n = 958) for predefined, prospective
      biomarker analyses. RESULTS: Of evaluable samples, 14% were EGFR mutation
      positive, 35% were EGFR FISH positive, 88% were EGFR protein expression positive,
      and 13% were KRAS mutation positive. Compared with the overall study population,
      in which progression-free survival (PFS) [hazard ratio (HR) = 0.79] but not OS
      (HR = 0.91) were significantly improved with vandetanib, there was greater
      relative clinical benefit for patients with EGFR mutation-positive tumors [PFS HR
      0.51, confidence interval (CI) 0.25-1.06 and OS HR 0.46, CI 0.14-1.57] and EGFR
      FISH-positive tumors (PFS HR 0.61, CI 0.39-0.94 and OS HR 0.48, CI 0.28-0.84).
      Similarly, patients with EGFR mutation or FISH-positive tumor samples who
      received vandetanib had an increased chance of objective tumor response (odds
      ratios 3.34, CI 0.8-13.89, and 3.90, CI 1.02-14.82, respectively). There did not
      appear to be benefit for vandetanib in patients with KRAS mutation-positive
      tumors. CONCLUSIONS: High EGFR gene copy number or activating EGFR mutations may
      identify patient subgroups who receive increased clinical benefit from vandetanib
      in combination with docetaxel in second-line NSCLC. CLINICALTRIALSGOV:
      NCT00312377.

PMID- 25057174
TI  - Continuous versus intermittent chemotherapy strategies in metastatic colorectal
      cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: An important goal of intermittent strategies of delivering systemic
      treatment as first-line treatment of metastatic colorectal cancer (mCRC) is to
      maintain efficacy while improving patients' quality of life (QoL). Given the
      varying impact on efficacy demonstrated in individual randomized, controlled
      trials (RCTs), a systematic review and meta-analysis of RCTs of these
      intermittent strategies was carried out. DESIGN: Relevant databases were
      systematically searched for the period 2000-2014. RCTs that compared a continuous
      versus intermittent strategy of delivering systemic treatment were identified by
      a systematic review. Overall survival (OS) hazard ratios (HRs) were extracted
      from the most recently reported trial results. The results of identified trials
      were clinically homogeneous so the data were pooled using Review Manager software
      (RevMan 5.1). RESULTS: Eleven RCTs were identified (n = 4 854). For the eight (n
      = 4508) trials with available HRs, the treatment patients received after
      induction was: none (five trials, n = 3036), fluoropyrimidine (one trial, n =
      620), and biologic (two trials, n = 852). There were no statistically significant
      survival differences observed between the continuous and intermittent
      chemotherapy strategies. There was no statistically significant difference
      observed between continuous and intermittent strategies [HR = 1.03, 95%
      confidence interval (CI) 0.96-1.10, P = 0.38)]. Subgroup analyses demonstrated
      results were generally robust across induction and maintenance regimens. One
      subgroup analysis of the three trials (CAIRO3, OPTIMOX2, COIN, n = 2403) with
      combination treatment induction and no maintenance until progression revealed a
      statistically, but nonclinically significant benefit for continuous treatment (HR
      = 1.10, 95% CI 1.00-1.20, P = 0.049). QoL life was either the same in both arms
      in two trials (n = 912) or improved in the intermittent strategy arm in one trial
      (n = 1630). CONCLUSION: Intermittent strategies of delivering systemic treatment
      of mCRC do not result in a clinically significant reduction in OS compared with a
      continuous strategy of delivery, and should be part of an informed discussion of
      treatment options with patients with mCRC.

PMID- 25057175
TI  - Prognostic information of a previously diagnosed sister is an independent
      prognosticator for a newly diagnosed sister with breast cancer.
AB  - BACKGROUND: Breast cancer survival has been shown to be associated among
      relatives. In this study, we used a population-based cohort of Swedish sisters,
      both diagnosed with breast cancer, to determine whether prognostic information of
      a previously diagnosed sibling is useful for the clinical management of a newly
      diagnosed sibling. PATIENTS AND METHODS: The population-based cohort included all
      sister pairs, 1617 sisters, diagnosed with breast cancer in Sweden, from 1
      January 1992, through 31 December 2006, with complete follow-up. All information
      was collected manually from original pathology reports and patient records. The
      Kappa statistic was used to measure the agreement of primary tumor
      characteristics between the sisters. We modeled the breast cancer-specific
      survival using multivariate (Cox) proportional hazard analyses in two steps
      categorizing the older sister's survival. RESULTS: Estrogen receptor status was
      the only tumor characteristic significantly associated between the sisters [kappa
      0.18 (95% confidence interval (CI) 0.089-0.27)]. Younger sisters with poor older
      sister survival showed significantly worse survival compared with patients with
      good older sister survival (log rank, P = 0.017). A twofold increased hazard
      ratio (HR) for death from breast cancer was found in younger sisters with poor
      older sister survival compared with patients with good sister survival [HR 2.56
      (95% CI 1.16-5.65)], adjusting for age and calendar period of diagnosis,
      socioeconomic factors, number of children and hospital of primary tumor
      diagnosis. When further adjusting for primary tumor characteristics and adjuvant
      therapy, the risk for death from breast cancer in younger sisters with poor older
      sister survival became more pronounced [HR 3.35 (1.34-8.34)]. CONCLUSIONS: Our
      findings derived from a population-based cohort of Swedish sister pairs suggest
      that breast cancer-specific survival is inherited independent of tumor
      characteristics and treatment in the sibling later diagnosed with the disease.
      Prognostic information of a previously diagnosed sibling with breast cancer could
      be important in the clinical management.

PMID- 25057176
TI  - Treating breast cancer with trabectedin: a new arsenal.

PMID- 25057177
TI  - Phase I trial of rituximab, cladribine, and temsirolimus (RCT) for initial
      therapy of mantle cell lymphoma.
AB  - BACKGROUND: We conducted this trial to determine the maximum tolerated dose (MTD)
      of temsirolimus added to an established regimen comprised of rituximab and
      cladribine for the initial treatment of mantle cell lymphoma. PATIENTS AND
      METHODS: A standard phase I cohort of three study design was utilized. The fixed
      doses of rituximab and cladribine were 375 mg/m(2) i.v. day 1 and 5 mg/m(2)/day
      i.v. days 1-5 of a 28-day cycle, respectively. There were five planned
      temsirolimus i.v. dose levels: 15 mg day 1; 25 mg day 1; 25 mg days 1 and 15; 25
      mg days 1, 8 and 15; and 25 mg days 1, 8, 15, and 22. RESULTS: Seventeen patients
      were treated: three each at levels 1-4 and five at dose level 5. The median age
      was 75 years (52-86 years). Mantle Cell International Prognostic Index (MIPI)
      scores were low in 6% (1), intermediate in 59% (10), and high in 35% (6) of
      patients. Five patients were treated at level 5 without dose limiting toxicity.
      Hematologic toxicity was frequent: grade 3 anemia in 12%, grade 3
      thrombocytopenia in 41%, grade 4 thrombocytopenia in 24%, grade 3 neutropenia in
      6%, and grade 4 neutropenia in 18% of patients. The overall response rate (ORR)
      was 94% with 53% complete response and 41% partial response. The median
      progression-free survival was 18.7 months. CONCLUSIONS: Temsirolimus 25 mg i.v.
      weekly may be safely added to rituximab and cladribine at 375 mg/m(2) i.v. day 1
      and 5 mg/m(2)/day i.v. days 1-5 of a 28-day cycle, respectively. This regimen had
      promising preliminary activity in an elderly cohort of patients with mantle cell
      lymphoma. CLINICALTRIALSGOV IDENTIFIER: NCT00787969.

PMID- 25057179
TI  - MBDA: what is it good for?

PMID- 25057180
TI  - Positron emission tomography in giant cell arteritis: a new diagnostic tool?

PMID- 25057178
TI  - Being overweight or obese and risk of developing rheumatoid arthritis among
      women: a prospective cohort study.
AB  - OBJECTIVES: To examine the relationship between being overweight or obese and
      developing rheumatoid arthritis (RA) in two large prospective cohorts, the
      Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). METHODS: We
      followed 109 896 women enrolled in NHS and 108 727 in NHSII who provided
      lifestyle, environmental exposure and anthropometric information through biennial
      questionnaires. We assessed the association between time-varying and cumulative
      Body Mass Index (BMI) in WHO categories of normal, overweight and obese (18.5
      <25, 25.0-<30, >=30.0 kg/m(2)) and incident RA meeting the 1987 American College
      of Rheumatology (ACR) criteria. We estimated HRs for overall RA and serologic
      subtypes with Cox regression models adjusted for potential confounders. We
      repeated analyses restricted to RA diagnosed at age 55 years or younger. RESULTS:
      During 2 765 195 person-years of follow-up (1976-2008) in NHS and 1 934 518
      person-years (1989-2009) in NHSII, we validated 1181 incident cases of RA (826 in
      NHS, 355 in NHSII). There was a trend toward increased risk of all RA among
      overweight and obese women (HR (95% CI) 1.37 (0.95 to 1.98) and 1.37 (0.91,
      2.09), p for trend=0.068). Among RA cases diagnosed at age 55 years or younger,
      this association appeared stronger (HR 1.45 (1.03 to 2.03) for overweight and
      1.65 (1.34 to 2.05) for obese women (p trend <0.001)). Ten cumulative years of
      being obese, conferred a 37% increased risk of RA at younger ages (HR 1.37 (1.11
      to 1.69)). CONCLUSIONS: Risks of seropositive and seronegative RA were elevated
      among overweight and obese women, particularly among women diagnosed with RA at
      earlier ages.

PMID- 25057181
TI  - CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic
      arthritis.
AB  - OBJECTIVES: Juvenile idiopathic arthritis (JIA) is considered a complex genetic
      autoimmune disease. We investigated the association of genetic variants
      previously implicated in JIA, autoimmunity and/or immunoregulation, with
      susceptibility to JIA. METHODS: A genetic association study was performed in 639
      JIA patients and 1613 healthy controls of northwest European descent. Ninety
      three single nucleotide polymorphisms (SNP) were genotyped in a candidate gene
      approach. Results of the entire JIA patient group (all subtypes) were compared
      with results obtained, alternatively, with a clinically homogeneous patient group
      including only oligoarticular and rheumatoid factor (RF) negative polyarticular
      JIA patients (n=493). Meta-analyses were performed for all SNPs that have been
      typed in other Caucasian JIA cohorts before. RESULTS: SNPs in or near PTPN22,
      VTCN1, the IL2-IL21 region, ANKRD55 and TNFA were confirmed to be associated with
      JIA (p<0.05), strengthening the evidence for involvement of these genes in JIA.
      In the majority of these replicated SNPs, effect sizes were larger when analysing
      a homogeneous patient cohort than when analysing all subtypes. We identified two
      novel associations with oligoarticular and RF-negative polyarticular JIA: CD226
      rs763361 (OR 1.30, 95% CI 1.12 to 1.51, p=0.0006) and CD28 rs1980422 (OR 1.29,
      95% CI 1.07 to 1.55, p=0.008). Meta-analyses including reported studies confirmed
      the association of both SNPs with susceptibility to JIA (OR 1.16, p=0.001 and OR
      1.18, p=0.001, for rs763361 and rs1980422, respectively). CONCLUSIONS: The CD226
      gene has been identified as novel association with JIA, and a SNP near CD28 as a
      suggestive association. Both genes are probable candidate risk factors, since
      they are involved in costimulation of T cells.

PMID- 25057182
TI  - The TRIFRA trial: efforts employed to minimise expectation bias.

PMID- 25057183
TI  - A robust association test for detecting genetic variants with heterogeneous
      effects.
AB  - One common strategy for detecting disease-associated genetic markers is to
      compare the genotype distributions between cases and controls, where cases have
      been diagnosed as having the disease condition. In a study of a complex disease
      with a heterogeneous etiology, the sampled case group most likely consists of
      people having different disease subtypes. If we conduct an association test by
      treating all cases as a single group, we maximize our chance of finding genetic
      risk factors with a homogeneous effect, regardless of the underlying disease
      etiology. However, this strategy might diminish the power for detecting risk
      factors whose effect size varies by disease subtype. We propose a robust
      statistical procedure to identify genetic risk factors that have either a uniform
      effect for all disease subtypes or heterogeneous effects across different
      subtypes, in situations where the subtypes are not predefined but can be
      characterized roughly by a set of clinical and/or pathologic markers. We
      demonstrate the advantage of the new procedure through numeric simulation studies
      and an application to a breast cancer study. 

PMID- 25057184
TI  - Structural glaucomatous progression before and after occurrence of an optic disc
      haemorrhage.
AB  - BACKGROUND: An optic disc haemorrhage (DH) has been associated with subsequent
      structural glaucoma progression, but it is unknown if there is structural
      progression prior to a DH. We evaluated a cohort of patients to determine whether
      structural progression occurs before a DH, after a DH or is simply associated
      with a DH. METHODS: Eyes meeting inclusion criteria were placed into two groups.
      Group 1 included eyes that each had a baseline photograph of the optic nerve and
      a photograph with a DH at follow-up. Group 2 included eyes that each had a
      photograph of the optic nerve with a DH at baseline and a photograph at follow
      up. Flicker images were created and graded by two ophthalmologists for structural
      glaucomatous change. We compared the proportion of structural progressors between
      Groups 1 and 2. Patient characteristics were also compared between the two
      groups. RESULTS: 49 patients and 51 unique eyes were included. Groups 1 and 2 had
      28 and 38 sets of photographs, respectively. The proportion of global progression
      in Groups 1 and 2 were 21.4% and 39.5%, respectively (p=0.12). No significant
      differences in any structural progression feature and patient characteristics
      (besides age at time of DH (p=0.04) between the two groups were found.
      CONCLUSIONS: Patients show structural glaucomatous progression before and after
      the event of a disc haemorrhage without significant differences. This suggests
      that a DH is an ongoing structural progression in glaucoma and may not be a
      discrete event that leads to subsequent progression.

PMID- 25057185
TI  - Gene expression profiles induced by growth factors in in vitro cultured
      osteoblasts.
AB  - OBJECTIVES: Effects of insulin-like growth factor 1 (IGF1), fibroblast growth
      factor 2 (FGF2) and bone morphogenetic protein 2 (BMP2) on the expression of
      genes involved in the proliferation and differentiation of osteoblasts in culture
      were analysed. The best sequence of growth factor addition that induces expansion
      of cells before their differentiation was sought. METHODS: Primary human
      osteoblasts in in vitro culture were treated with IGF1, BMP2 or FGF2 (10 ng/ml)
      for 24 hours (IGF1) or 48 hours (BMP2 and FGF2). Experiments were performed
      during the exponential growth phase with approximately 1e7 cells per 75 cm(2)
      flask. mRNA was reverse transcribed directly and analysed using RT-PCR Taqman
      assays. Expression levels of key genes involved in cell growth and
      differentiation (CDH11, TNFRSF11B, RUNX2, POSTN, ALP, WNT5A, LEF1, HSPA5, FOS,
      p21) were monitored using RT-PCR with gene-specific Taqman probes. RESULTS:
      Autocrine expression of BMP2 is stimulated by FGF2 and BMP2 itself. BMP2 and FGF2
      act as proliferative factors as indicated by reduced expression of ALP and POSTN,
      whereas IGF1 exhibits a more subtle picture: the Wingless und Int-1 (Wnt)
      signalling pathway and the Smad pathway, but not p38 mitogen-activated protein
      (MAP) kinase signalling, were shown to be activated by IGF1, leading to
      proliferation and differentiation of the cells. CONCLUSIONS: For future use of
      autologous bone cells in the management of bony defects, new treatment options
      take advantage of growth factors and differentiation factors. Thus, our results
      might help to guide the timely application of these factors for the expansion and
      subsequent differentiation of osteoblastic cells in culture. Cite this article:
      Bone Joint Res 2014;3:236-40.

PMID- 25057186
TI  - Non-neuronal cells exacerbate beta-amyloid aggregation in the aged brain.

PMID- 25057187
TI  - Modeling forces and moments at the base of a rat vibrissa during noncontact
      whisking and whisking against an object.
AB  - During exploratory behavior, rats brush and tap their whiskers against objects,
      and the mechanical signals so generated constitute the primary sensory variables
      upon which these animals base their vibrissotactile perception of the world. To
      date, however, we lack a general dynamic model of the vibrissa that includes the
      effects of inertia, damping, and collisions. We simulated vibrissal dynamics to
      compute the time-varying forces and bending moment at the vibrissa base during
      both noncontact (free-air) whisking and whisking against an object (collision).
      Results show the following: (1) during noncontact whisking, mechanical signals
      contain components at both the whisking frequency and also twice the whisking
      frequency (the latter could code whisking speed); (2) when rats whisk
      rhythmically against an object, the intrinsic dynamics of the vibrissa can be as
      large as many of the mechanical effects of the collision, however, the axial
      force could still generate responses that reliably indicate collision based on
      thresholding; and (3) whisking velocity will have only a small effect on the
      transient response generated during a whisker-object collision. Instead, the
      transient response will depend in large part on how the rat chooses to decelerate
      its vibrissae after the collision. The model allows experimentalists to estimate
      error bounds on quasi-static descriptions of vibrissal shape, and its predictions
      can be used to bound realistic expectations from neurons that code vibrissal
      sensing. We discuss the implications of these results under the assumption that
      primary sensory neurons of the trigeminal ganglion are sensitive to various
      combinations of mechanical signals. 

PMID- 25057188
TI  - Deletion of interleukin-6 signal transducer gp130 in small sensory neurons
      attenuates mechanonociception and down-regulates TRPA1 expression.
AB  - Glycoprotein 130 (gp130) is the signal transducing receptor subunit for cytokines
      of the interleukin-6 (IL-6) family, and it is expressed in a multitude of cell
      types of the immune and nervous system. IL-6-like cytokines are not only key
      regulators of innate immunity and inflammation but are also essential factors for
      the differentiation and development of the somatosensory system. Mice with a null
      mutation of gp130 in primary nociceptive afferents (SNS-gp130(-/-)) are largely
      protected from hypersensitivity to mechanical stimuli in mouse models of
      pathological pain. Therefore, we set out to investigate how neuronal gp130
      regulates mechanonociception. SNS-gp130(-/-) mice revealed reduced
      mechanosensitivity to high mechanical forces in the von Frey assay in vivo, and
      this was associated with a reduced sensitivity of nociceptive primary afferents
      in vitro. Together with these findings, transient receptor potential ankyrin 1
      (TRPA1) mRNA expression was significantly reduced in DRG from SNS-gp130(-/-)
      mice. This was also reflected by a reduced number of neurons responding with
      calcium transients to TRPA1 agonists in primary DRG cultures. Downregulation of
      Trpa1 expression was predominantly discovered in nonpeptidergic neurons, with the
      deficit becoming evident during stages of early postnatal development. Regulation
      of Trpa1 mRNA expression levels downstream of gp130 involved the classical Janus
      kinase family-signal transducer and activator of transcription pathway. Our
      results closely link proinflammatory cytokines to the expression of TRPA1, both
      of which have been shown to contribute to hypersensitive pain states. We suggest
      that gp130 has an essential role in mechanonociception and in the regulation of
      TRPA1 expression. 

PMID- 25057189
TI  - A shared, flexible neural map architecture reflects capacity limits in both
      visual short-term memory and enumeration.
AB  - Human cognition is characterized by severe capacity limits: we can accurately
      track, enumerate, or hold in mind only a small number of items at a time. It
      remains debated whether capacity limitations across tasks are determined by a
      common system. Here we measure brain activation of adult subjects performing
      either a visual short-term memory (vSTM) task consisting of holding in mind
      precise information about the orientation and position of a variable number of
      items, or an enumeration task consisting of assessing the number of items in
      those sets. We show that task-specific capacity limits (three to four items in
      enumeration and two to three in vSTM) are neurally reflected in the activity of
      the posterior parietal cortex (PPC): an identical set of voxels in this region,
      commonly activated during the two tasks, changed its overall response profile
      reflecting task-specific capacity limitations. These results, replicated in a
      second experiment, were further supported by multivariate pattern analysis in
      which we could decode the number of items presented over a larger range during
      enumeration than during vSTM. Finally, we simulated our results with a
      computational model of PPC using a saliency map architecture in which the level
      of mutual inhibition between nodes gives rise to capacity limitations and
      reflects the task-dependent precision with which objects need to be encoded (high
      precision for vSTM, lower precision for enumeration). Together, our work supports
      the existence of a common, flexible system underlying capacity limits across
      tasks in PPC that may take the form of a saliency map. 

PMID- 25057190
TI  - Genetic removal of matrix metalloproteinase 9 rescues the symptoms of fragile X
      syndrome in a mouse model.
AB  - Fmr1 knock-out (ko) mice display key features of fragile X syndrome (FXS),
      including delayed dendritic spine maturation and FXS-associated behaviors, such
      as poor socialization, obsessive-compulsive behavior, and hyperactivity. Here we
      provide conclusive evidence that matrix metalloproteinase-9 (MMP-9) is necessary
      to the development of FXS-associated defects in Fmr1 ko mice. Genetic disruption
      of Mmp-9 rescued key aspects of Fmr1 deficiency, including dendritic spine
      abnormalities, abnormal mGluR5-dependent LTD, as well as aberrant behaviors in
      open field and social novelty tests. Remarkably, MMP-9 deficiency also corrected
      non-neural features of Fmr1 deficiency-specifically macroorchidism-indicating
      that MMP-9 dysregulation contributes to FXS-associated abnormalities outside the
      CNS. Further, MMP-9 deficiency suppressed elevations of Akt, mammalian target of
      rapamycin, and eukaryotic translation initiation factor 4E phosphorylation seen
      in Fmr1 ko mice, which are also associated with other autistic spectrum
      disorders. These findings establish that MMP-9 is critical to the mechanisms
      responsible for neural and non-neural aspects of the FXS phenotype. 

PMID- 25057191
TI  - Cerebellar encoding of multiple candidate error cues in the service of motor
      learning.
AB  - For learning to occur through trial and error, the nervous system must
      effectively detect and encode performance errors. To examine this process, we
      designed a set of oculomotor learning tasks with more than one visual object
      providing potential error cues, as would occur in a natural visual scene. A task
      relevant visual target and a task-irrelevant visual background both influenced
      vestibulo-ocular reflex learning in rhesus monkeys. Thus, motor learning does not
      identify a single error cue based on behavioral relevance, but can be
      simultaneously influenced by more than one cue. Moreover, the relative weighting
      of the different cues could vary. If the speed of the visual target's motion on
      the retina was low (?1 degrees /s), background motion dominated learning, but if
      target speed was high, the effects of the background were suppressed. The target
      and background motion had similar, nonlinear effects on the putative neural
      instructive signals carried by cerebellar climbing fibers, but with a stronger
      influence of the background on the climbing fibers than on learning. In contrast,
      putative neural instructive signals carried by the simple spikes of Purkinje
      cells were influenced solely by the motion of the visual target. Because they are
      influenced by different cues during training, joint control of learning by the
      climbing fibers and Purkinje cells may expand the learning capacity of the
      cerebellar circuit. 

PMID- 25057193
TI  - Orbitofrontal cortex volume in area 11/13 predicts reward devaluation, but not
      reversal learning performance, in young and aged monkeys.
AB  - The orbitofrontal cortex (OFC) and amygdala are both necessary for decisions
      based on expected outcomes. Although behavioral and imaging data suggest that
      these brain regions are affected by advanced age, the extent to which aging
      alters appetitive processes coordinated by the OFC and the amygdala is unknown.
      In the current experiment, young and aged bonnet macaques were trained on OFC-
      and amygdala-dependent tasks that test the degree to which response selection is
      guided by reward value and can be adapted when expected outcomes change. To
      assess whether the structural integrity of these regions varies with levels of
      performance on reward devaluation and object reversal tasks, volumes of areas
      11/13 and 14 of the OFC, central/medial (CM), and basolateral (BL) nuclei of the
      amygdala were determined from high-resolution anatomical MRIs. With age, there
      were significant reductions in OFC, but not CM and BL, volume. Moreover, the aged
      monkeys showed impairments in the ability to associate an object with a higher
      value reward, and to reverse a previously learned association. Interestingly,
      greater OFC volume of area 11/13, but not 14, was significantly correlated with
      an animal's ability to anticipate the reward outcome associated with an object,
      and smaller BL volume was predictive of an animal's tendency to choose a higher
      value reward, but volume of neither region correlated with reversal learning.
      Together, these data indicate that OFC volume has an impact on monkeys' ability
      to guide choice behavior based on reward value but does not impact ability to
      reverse a previously learned association. 

PMID- 25057192
TI  - Mutant beta-III spectrin causes mGluR1alpha mislocalization and functional
      deficits in a mouse model of spinocerebellar ataxia type 5.
AB  - Spinocerebellar ataxia type 5 (SCA5), a dominant neurodegenerative disease
      characterized by profound Purkinje cell loss, is caused by mutations in SPTBN2, a
      gene that encodes beta-III spectrin. SCA5 is the first neurodegenerative disorder
      reported to be caused by mutations in a cytoskeletal spectrin gene. We have
      developed a mouse model to understand the mechanistic basis for this disease and
      show that expression of mutant but not wild-type beta-III spectrin causes
      progressive motor deficits and cerebellar degeneration. We show that endogenous
      beta-III spectrin interacts with the metabotropic glutamate receptor 1alpha
      (mGluR1alpha) and that mice expressing mutant beta-III spectrin have cerebellar
      dysfunction with altered mGluR1alpha localization at Purkinje cell dendritic
      spines, decreased mGluR1-mediated responses, and deficient mGluR1-mediated long
      term potentiation. These results indicate that mutant beta-III spectrin causes
      mislocalization and dysfunction of mGluR1alpha at dendritic spines and connects
      SCA5 with other disorders involving glutamatergic dysfunction and synaptic
      plasticity abnormalities. 

PMID- 25057194
TI  - Additive gene-environment effects on hippocampal structure in healthy humans.
AB  - Hippocampal volume loss has been related to chronic stress as well as genetic
      factors. Although genetic and environmental variables affecting hippocampal
      volume have extensively been studied and related to mental illness, limited
      evidence is available with respect to G * E interactions on hippocampal volume.
      The present MRI study investigated interaction effects on hippocampal volume
      between three well-studied functional genetic variants (COMT Val158Met, BDNF
      Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of
      environmental adversity (life events questionnaire) in a large sample of healthy
      humans (n = 153). All three variants showed significant interactions with
      environmental adversity with respect to hippocampal volume. Observed effects were
      additive by nature and driven by both recent as well as early life events. A
      consecutive analysis of hippocampal subfields revealed a spatially distinct
      profile for each genetic variant suggesting a specific role of 5-HTTLPR for the
      subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3
      volume changes. The present study underscores the importance of G * E
      interactions as determinants of hippocampal volume, which is crucial for the
      neurobiological understanding of stress-related conditions, such as mood
      disorders or post-traumatic stress disorder (PTSD). 

PMID- 25057195
TI  - Neuronal ensemble synchrony during human focal seizures.
AB  - Seizures are classically characterized as the expression of hypersynchronous
      neural activity, yet the true degree of synchrony in neuronal spiking (action
      potentials) during human seizures remains a fundamental question. We quantified
      the temporal precision of spike synchrony in ensembles of neocortical neurons
      during seizures in people with pharmacologically intractable epilepsy. Two
      seizure types were analyzed: those characterized by sustained gamma (~40-60 Hz)
      local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ~3
      Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band
      seizures, where neuronal spiking remained highly irregular and asynchronous. In
      SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced
      synchrony at a coarse 50-100 ms level. In addition, transient fine synchrony
      occurred primarily during the initial ~20 ms period of the SWC spike phase and
      varied across subjects and seizures. Sporadic coherence events between neuronal
      population spike counts and LFPs were observed during SWC seizures in high (~80
      Hz) gamma-band and during high-frequency oscillations (~130 Hz). Maximum entropy
      models of the joint neuronal spiking probability, constrained only on single
      neurons' nonstationary coarse spiking rates and local network activation,
      explained most of the fine synchrony in both seizure types. Our findings indicate
      that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band,
      seizures, and primarily during the initial phase of SWC spikes. Furthermore,
      these fine synchrony events result mostly from transient increases in overall
      neuronal network spiking rates, rather than changes in precise spiking
      correlations between specific pairs of neurons. 

PMID- 25057196
TI  - Cocaine abuse in humans is not associated with increased microglial activation:
      an 18-kDa translocator protein positron emission tomography imaging study with
      [11C]PBR28.
AB  - Basic science investigations have consistently shown that repeated exposure to
      psychostimulant drugs, such as cocaine, activate the immune response and lead to
      inflammatory changes in the brain. No previous in vivo studies have confirmed
      this observation in chronic cocaine-abusing humans. To test this hypothesis, we
      used positron emission tomography imaging to measure the binding of [(11)C]PBR28
      to the 18 kDa translocator protein (TSPO), a marker for microglial activation in
      a group of 15 recently abstinent cocaine abusers and 17 matched healthy controls.
      [(11)C]PBR28 volumes of distribution expressed relative to total plasma ligand
      concentration (VT) were measured in subjects with kinetic analysis using the
      arterial input function. Subjects were also genotyped for the TSPO alanine147
      threonine (Ala147Thr, rs6971) polymorphism that has been shown to influence the
      in vivo binding of PBR28 to TSPO. Consistent with previous reports, the TSPO
      Ala147Thr genotype predicted the in vivo binding of [(11)C]PBR28. No significant
      differences in [(11)C]PBR28 VT were observed in the cortical and subcortical
      regions in cocaine abusers compared with healthy controls. The results of this in
      vivo study do not support increased TSPO expression and, by extension, microglial
      activation in chronic cocaine-abusing humans. Further research with more direct
      markers of microglial activation is necessary to conclusively rule out
      neuroinflammation in cocaine dependence. 

PMID- 25057197
TI  - AAVshRNA-mediated suppression of PTEN in adult rats in combination with salmon
      fibrin administration enables regenerative growth of corticospinal axons and
      enhances recovery of voluntary motor function after cervical spinal cord injury.
AB  - Conditional genetic deletion of phosphatase and tensin homolog (PTEN) in the
      sensorimotor cortex of neonatal mice enables regeneration of corticospinal tract
      (CST) axons after spinal cord injury (SCI). The present study addresses three
      questions: (1) whether PTEN knockdown in adult rats by nongenetic techniques
      enables CST regeneration, (2) whether interventions to enable CST regeneration
      enhance recovery of voluntary motor function, and (3) whether delivery of salmon
      fibrin into the injury site further enhances CST regeneration and motor recovery.
      Adult rats were trained in a staircase-reaching task and then received either
      intracortical injections of AAVshPTEN to delete PTEN or a control vector
      expressing shRNA for luciferase (AAVshLuc). Rats then received cervical dorsal
      hemisection injuries and salmon fibrin was injected into the injury site in half
      the rats, yielding four groups (AAVshPTEN, AAVshLuc, AAVshPTEN + fibrin, and
      AAVshLuc + fibrin). Forepaw function was assessed for 10 weeks after injury and
      CST axons were traced by injecting biotin-conjugated dextran amine into the
      sensorimotor cortex. Rats that received AAVshPTEN alone did not exhibit improved
      motor function, whereas rats that received AAVshPTEN and salmon fibrin had
      significantly higher forelimb-reaching scores. Tract tracing revealed that CST
      axons extended farther caudally in the group that received AAVshPTEN and salmon
      fibrin versus other groups. There were no significant differences in lesion size
      between the groups. Together, these data suggest that the combination of PTEN
      deletion and salmon fibrin injection into the lesion can significantly improve
      voluntary motor function after SCI by enabling regenerative growth of CST axons. 

PMID- 25057198
TI  - Differential neuronal representation of spatial attention dependent on relative
      target locations during multiple object tracking.
AB  - Humans can simultaneously track multiple moving objects with attention. The
      number of objects that can be tracked is known to be larger when visual stimuli
      are presented bilaterally rather than presented unilaterally. To elucidate the
      underlying neuronal mechanism, we trained monkeys to covertly track a single or
      multiple object(s). We found that neurons in the lateral prefrontal cortex
      exhibited greater activity for the target passing through the receptive field
      (RF) than for distractors. During multiple-object tracking, response enhancement
      for one target presented in the RF was stronger when the other target was located
      in the opposite than the same visual hemifield. Because the neuronal modulation
      did not differ depending on relative target locations with respect to upper and
      lower visual hemifields, the distance between the targets does not explain the
      results. We propose that inherent, anatomical separation of visual processing for
      contralateral and ipsilateral visual fields might constrain cognitive capacity. 

PMID- 25057199
TI  - Implicit perceptual memory modulates early visual processing of ambiguous images.
AB  - The way we perceive the present visual environment is influenced by past visual
      experiences. Here we investigated the neural basis of such experience dependency.
      We repeatedly presented human observers with an ambiguous visual stimulus
      (structure-from-motion) that can give rise to two distinct perceptual
      interpretations. Past visual experience is known to influence the perception of
      such stimuli. We recorded fast dynamics of neural activity shortly after stimulus
      onset using event-related electroencephalography. The number of previous
      occurrences of a certain percept modulated early posterior brain activity
      starting as early as 50 ms after stimulus onset. This modulation developed across
      hundreds of percept repetitions, reflecting several minutes of accumulating
      perceptual experience. Importantly, there was no such modulation when the mere
      number of previous stimulus presentations was considered regardless of how they
      were perceived. This indicates that the effect depended on previous perception
      rather than previous visual input. The short latency and posterior scalp location
      of the effect suggest that perceptual history modified bottom-up stimulus
      processing in early visual cortex. We propose that bottom-up neural responses to
      a given visual presentation are shaped, in part, by feedback modulation that
      occurred during previous presentations, thus allowing these responses to be
      biased in light of previous perceptual decisions. 

PMID- 25057200
TI  - Developmental switch of leptin signaling in arcuate nucleus neurons.
AB  - Leptin is well known for its role in the regulation of energy homeostasis in
      adults, a mechanism that at least partially results from the inhibition of the
      activity of NPY/AgRP/GABA neurons (NAG) in the arcuate nucleus of the
      hypothalamus (ARH). During early postnatal development in the rodent, leptin
      promotes axonal outgrowth from ARH neurons, and preautonomic NAG neurons are
      particularly responsive to leptin's trophic effects. To begin to understand how
      leptin could simultaneously promote axonal outgrowth from and inhibit the
      activity of NAG neurons, we characterized the electrochemical effects of leptin
      on NAG neurons in mice during early development. Here, we show that NAG neurons
      do indeed express a functional leptin receptor throughout the early postnatal
      period in the mouse; however, at postnatal days 13-15, leptin causes membrane
      depolarization in NAG neurons, rather than the expected hyperpolarization. Leptin
      action on NAG neurons transitions from stimulatory to inhibitory in the
      periweaning period, in parallel with the acquisition of functional ATP-sensitive
      potassium channels. These findings are consistent with the idea that leptin
      provides an orexigenic drive through the NAG system to help rapidly growing pups
      meet their energy requirements. 

PMID- 25057201
TI  - Attentional modulation of the inner ear: a combined otoacoustic emission and EEG
      study.
AB  - Attending to a single stimulus in a complex multisensory environment requires the
      ability to select relevant information while ignoring distracting input. The
      underlying mechanism and involved neuronal levels of this attentional gain
      control are still a matter of debate. Here, we investigated the influence of
      intermodal attention on different levels of auditory processing in humans. It is
      known that the activity of the cochlear amplifier can be modulated by efferent
      neurons of the medial olivocochlear complex. We used distortion product
      otoacoustic emission (DPOAE) measurements to monitor cochlear activity during an
      intermodal cueing paradigm. Simultaneously, central auditory processing was
      assessed by electroencephalography (EEG) with a steady-state paradigm targeting
      early cortical responses and analysis of alpha oscillations reflecting higher
      cognitive control of attentional modulation. We found effects of selective
      attention at all measured levels of the auditory processing: DPOAE levels
      differed significantly between periods of visual and auditory attention, showing
      a reduction during visual attention, but no change during auditory attention.
      Primary auditory cortex activity, as measured by the auditory steady-state
      response (ASSR), differed between conditions, with higher ASSRs during auditory
      than visual attention. Furthermore, the analysis of cortical oscillatory activity
      revealed increased alpha power over occipitoparietal and frontal regions during
      auditory compared with visual attention, putatively reflecting suppression of
      visual processing. In conclusion, this study showed both enhanced processing of
      attended acoustic stimuli in early sensory cortex and reduced processing of
      distracting input, both at higher cortical levels and at the most peripheral
      level of the hearing system, the cochlea. 

PMID- 25057202
TI  - Glycine transporter-1 controls nonsynaptic inhibitory actions of glycine
      receptors in the neonatal rat hippocampus.
AB  - Although functional glycinergic synapses have not been identified in the
      hippocampus, neurons in this area express Cl(-) permeable extrasynaptic glycine
      receptors (GlyRs). In experiments on CA3 pyramidal neurons on postnatal day 0-6
      rat hippocampal slices, we detected robust GlyR activity as a tonic current and
      as single-channel events. Glycine release was independent of neuronal activity or
      extracellular Ca(2+). The endogenous GlyR activity was strongly enhanced by
      inhibition of the glycine-transporter-1 (GlyT1). Blockade of GlyT1 also caused a
      profound increase in the baseline current induced by exogenous glycine.
      Inhibition of GlyT1 reduced the frequency of spontaneous network events known as
      field giant depolarizing potentials (fGDPs) and of the unit activity in the
      absence of synaptic transmission. This inhibitory action on fGDPs was mimicked by
      applying 2 MUm glycine or 0.1 MUm isoguvacine, a GABAA-receptor agonist.
      Furthermore, 2 MUm glycine suppressed unit spiking in the absence of synaptic
      transmission. Hence, despite the well known depolarizing Cl(-) equilibrium
      potential of neonatal hippocampal neurons, physiologically relevant extracellular
      glycine concentrations can exert an inhibitory action. The present data show
      that, akin to GABA uptake, GlyT1 exerts a powerful modulatory action on network
      events in the newborn hippocampus. 

PMID- 25057203
TI  - eIF2alpha dephosphorylation in basolateral amygdala mediates reconsolidation of
      drug memory.
AB  - Maladaptive memories elicited by exposure to environmental stimuli associated
      with drugs of abuse are often responsible for relapse among addicts. Interference
      with the reconsolidation of drug memory can inhibit drug seeking. Previous
      studies have indicated that the dephosphorylation of the eukaryotic initiation
      factor 2 alpha-subunit (eIF2alpha) plays an important role in synaptic plasticity
      and long-term memory consolidation, but its role in the reconsolidation of drug
      memory remains unknown. The amygdala is required for the reconsolidation of a
      destabilized drug memory after retrieval of drug-paired stimuli. Here, we used
      conditioned place preference (CPP) and self-administration procedures to
      determine whether amygdala eIF2alpha dephosphorylation is required for the
      reconsolidation of morphine and cocaine memories in rats. We found that the
      levels of eIF2alpha phosphorylation (Ser51) and activating transcription factor 4
      (ATF4) were decreased after reexposure to a previously morphine- or cocaine
      paired context (i.e., a memory retrieval procedure) in the basolateral amygdala
      (BLA) but not in the central amygdala. Intra-BLA infusions of Sal003, a selective
      inhibitor of eIF2alpha dephosphorylation, immediately after memory retrieval
      disrupted the reconsolidation of morphine- or cocaine-induced CPP, leading to a
      long-lasting suppression of drug-paired stimulus-induced craving. Advanced
      knockdown of ATF4 expression in the BLA by lentivirus-mediated short-hairpin RNA
      blocked the disruption of the reconsolidation of morphine-induced CPP induced by
      Sal003 treatment. Furthermore, inhibition of eIF2alpha dephosphorylation in the
      BLA immediately after light/tone stimulus retrieval decreased subsequent cue
      induced heroin-seeking behavior in the self-administration procedure. These
      results demonstrate that eIF2alpha dephosphorylation in the BLA mediates the
      memory reconsolidation of drug-paired stimuli. 

PMID- 25057205
TI  - Mutant huntingtin affects cortical progenitor cell division and development of
      the mouse neocortex.
AB  - A polyglutamine expansion in huntingtin (HTT) causes the specific death of adult
      neurons in Huntington's disease (HD). Most studies have thus focused on mutant
      HTT (mHTT) toxicity in adulthood, and its developmental effects have been largely
      overlooked. We found that mHTT caused mitotic spindle misorientation in cultured
      cells by altering the localization of dynein, NuMA, and the p150(Glued) subunit
      of dynactin to the spindle pole and cell cortex and of CLIP170 and p150(Glued) to
      microtubule plus-ends. mHTT also affected spindle orientation in dividing mouse
      cortical progenitors, altering the thickness of the developing cortex. The
      serine/threonine kinase Akt, which regulates HTT function, rescued the spindle
      misorientation caused by the mHTT, by serine 421 (S421) phosphorylation, in
      cultured cells and in mice. Thus, cortical development is affected in HD, and
      this early defect can be rescued by HTT phosphorylation at S421. 

PMID- 25057204
TI  - Leptin-induced spine formation requires TrpC channels and the CaM kinase cascade
      in the hippocampus.
AB  - Leptin is a critical neurotrophic factor for the development of neuronal pathways
      and synaptogenesis in the hypothalamus. Leptin receptors are also found in other
      brain regions, including the hippocampus, and a postnatal surge in leptin
      correlates with a time of rapid growth of dendritic spines and synapses in the
      hippocampus. Leptin is critical for normal hippocampal dendritic spine formation
      as db/db mice, which lack normal leptin receptor signaling, have a reduced number
      of dendritic spines in vivo. Leptin also positively influences hippocampal
      behaviors, such as cognition, anxiety, and depression, which are critically
      dependent on dendritic spine number. What is not known are the signaling
      mechanisms by which leptin initiates spine formation. Here we show leptin induces
      the formation of dendritic protrusions (thin headless, stubby and mushroom shaped
      spines), through trafficking and activation of TrpC channels in cultured
      hippocampal neurons. Leptin-activation of the TrpC current is dose dependent and
      blocked by targeted knockdown of the leptin receptor. The nonselective TrpC
      channel inhibitors SKF96365 and 2-APB or targeted knockdown of TrpC1 or 3, but
      not TrpC5, channels also eliminate the leptin-induced current. Leptin stimulates
      the phosphorylation of CaMKIgamma and beta-Pix within 5 min and their activation
      is required for leptin-induced trafficking of TrpC1 subunits to the membrane.
      Furthermore, we show that CaMKIgamma, CaMKK, beta-Pix, Rac1, and TrpC1/3 channels
      are all required for both the leptin-sensitive current and leptin-induced spine
      formation. These results elucidate a critical pathway underlying leptin's
      induction of dendritic morphological changes that initiate spine and excitatory
      synapse formation. 

PMID- 25057206
TI  - Frontal cortical and subcortical projections provide a basis for segmenting the
      cingulum bundle: implications for neuroimaging and psychiatric disorders.
AB  - The cingulum bundle (CB) is one of the brain's major white matter pathways,
      linking regions associated with executive function, decision-making, and emotion.
      Neuroimaging has revealed that abnormalities in particular locations within the
      CB are associated with specific psychiatric disorders, including depression and
      bipolar disorder. However, the fibers using each portion of the CB remain
      unknown. In this study, we used anatomical tract-tracing in nonhuman primates
      (Macaca nemestrina, Macaca fascicularis, Macaca mulatta) to examine the
      organization of specific cingulate, noncingulate frontal, and subcortical
      pathways through the CB. The goals were as follows: (1) to determine connections
      that use the CB, (2) to establish through which parts of the CB these fibers
      travel, and (3) to relate the CB fiber pathways to the portions of the CB
      identified in humans as neurosurgical targets for amelioration of psychiatric
      disorders. Results indicate that cingulate, noncingulate frontal, and subcortical
      fibers all travel through the CB to reach both cingulate and noncingulate
      targets. However, many brain regions send projections through only part, not all,
      of the CB. For example, amygdala fibers are not present in the caudal portion of
      the dorsal CB. These results allow segmentation of the CB into four unique zones.
      We identify the specific connections that are abnormal in psychiatric disorders
      and affected by neurosurgical interventions, such as deep brain stimulation and
      cingulotomy. 

PMID- 25057207
TI  - Downregulation of miR-23a and miR-27a following experimental traumatic brain
      injury induces neuronal cell death through activation of proapoptotic Bcl-2
      proteins.
AB  - MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene
      expression at the post-transcriptional level. To identify miRs that may regulate
      neuronal cell death after experimental traumatic brain injury (TBI), we profiled
      miR expression changes during the first several days after controlled cortical
      impact (CCI) in mice. miR-23a and miR-27a were rapidly downregulated in the
      injured cortex in the first hour after TBI. These changes coincided with
      increased expression of the proapoptotic Bcl-2 family members Noxa, Puma, and
      Bax. In an etoposide-induced in vitro model of apoptosis in primary cortical
      neurons, miR-23a and miR-27a were markedly downregulated as early as 1 h after
      exposure, before the upregulation of proapoptotic Bcl-2 family molecules.
      Administration of miR-23a and miR-27a mimics attenuated etoposide-induced changes
      in Noxa, Puma, and Bax, reduced downstream markers of caspase-dependent
      (cytochrome c release and caspase activation) and caspase-independent (apoptosis
      inducing factor release) pathways, and limited neuronal cell death. In contrast,
      miRs hairpin inhibitors enhanced etoposide-induced neuronal apoptosis and caspase
      activation. Importantly, administration of miR-23a and miR-27a mimics
      significantly reduced activation of Puma, Noxa, and Bax as well as attenuated
      markers of caspase-dependent and -independent apoptosis after TBI. Furthermore,
      miR-23a and miR-27a mimics significantly attenuated cortical lesion volume and
      neuronal cell loss in the hippocampus after TBI. These findings indicate that
      post-traumatic decreases in miR-23a and miR-27a contribute to neuronal cell death
      after TBI by upregulating proapoptotic Bcl-2 family members, thus providing a
      novel therapeutic target. 

PMID- 25057208
TI  - LMO4 functions as a negative regulator of sensory organ formation in the
      mammalian cochlea.
AB  - In mammals, formation of the auditory sensory organ (the organ of Corti) is
      restricted to a specialized area of the cochlea. However, the molecular
      mechanisms limiting sensory formation to this discrete region in the ventral
      cochlear duct are not well understood, nor is it known whether other regions of
      the cochlea have the competence to form the organ of Corti. Here we identify
      LMO4, a LIM-domain-only nuclear protein, as a negative regulator of sensory organ
      formation in the cochlea. Inactivation of Lmo4 in mice leads to an ectopic organ
      of Corti (eOC) located in the lateral cochlea. The eOC retains the features of
      the native organ, including inner and outer hair cells, supporting cells, and
      other nonsensory specialized cell types. However, the eOC shows an orientation
      opposite to the native organ, such that the eOC appears as a mirror-image
      duplication to the native organ of Corti. These data demonstrate a novel sensory
      competent region in the lateral cochlear duct that is regulated by LMO4 and may
      be amenable to therapeutic manipulation. 

PMID- 25057209
TI  - Random positions of dendritic spines in human cerebral cortex.
AB  - Dendritic spines establish most excitatory synapses in the brain and are located
      in Purkinje cell's dendrites along helical paths, perhaps maximizing the
      probability to contact different axons. To test whether spine helixes also occur
      in neocortex, we reconstructed >500 dendritic segments from adult human cortex
      obtained from autopsies. With Fourier analysis and spatial statistics, we
      analyzed spine position along apical and basal dendrites of layer 3 pyramidal
      neurons from frontal, temporal, and cingulate cortex. Although we occasionally
      detected helical positioning, for the great majority of dendrites we could not
      reject the null hypothesis of spatial randomness in spine locations, either in
      apical or basal dendrites, in neurons of different cortical areas or among spines
      of different volumes and lengths. We conclude that in adult human neocortex spine
      positions are mostly random. We discuss the relevance of these results for spine
      formation and plasticity and their functional impact for cortical circuits. 

PMID- 25057210
TI  - SCAMP5 plays a critical role in synaptic vesicle endocytosis during high neuronal
      activity.
AB  - Secretory carrier membrane protein 5 (SCAMP5), a recently identified candidate
      gene for autism, is brain specific and highly abundant in synaptic vesicles
      (SVs), but its function is currently unknown. Here, we found that knockdown (KD)
      of endogenous SCAMP5 by SCAMP5-specific shRNAs in cultured rat hippocampal
      neurons resulted in a reduction in total vesicle pool size as well as in
      recycling pool size, but the recycling/resting pool ratio was significantly
      increased. SCAMP5 KD slowed endocytosis after stimulation, but impaired it
      severely during strong stimulation. We also found that KD dramatically lowered
      the threshold of activity at which SV endocytosis became unable to compensate for
      the ongoing exocytosis occurring during a stimulus. Reintroducing shRNA-resistant
      SCAMP5 reversed these endocytic defects. Therefore, our results suggest that
      SCAMP5 functions during high neuronal activity when a heavy load is imposed on
      endocytosis. Our data also raise the possibility that the reduction in expression
      of SCAMP5 in autistic patients may be related to the synaptic dysfunction
      observed in autism. 

PMID- 25057211
TI  - The brain network underlying the recognition of hand gestures in the blind: the
      supramodal role of the extrastriate body area.
AB  - The visual perception of others' body parts is critical for understanding and
      imitating their behavior. The visual cortex in humans includes the extrastriate
      body area (EBA), which is a large portion of the occipitotemporal cortex that is
      selectively responsive to visually perceived body parts. Previous neuroimaging
      studies showed that the EBA not only receives sensory inputs regarding others'
      body information but also receives kinesthetic feedback regarding one's own
      actions. This finding raised the possibility that the EBA could be formed via
      nonvisual sensory modalities. However, the effect of visual deprivation on the
      formation of the EBA has remained largely unknown. Here, we used fMRI to
      investigate the effect of vision loss on the development of the EBA. Blind and
      sighted human subjects performed equally well in a haptic-identification task
      involving three categories of objects (hand shapes, toy cars, and teapots). The
      superior part (i.e., the middle temporal gyrus and angular gyrus) of the EBA and
      the supramarginal gyrus showed greater sensitivity to recognized hand shapes than
      to inanimate objects, regardless of the sensory modality and visual experience.
      Unlike the superior part of the EBA, the sensitivity of the inferior part (i.e.,
      the inferior temporal sulcus and middle occipital gyrus) depended on visual
      experience. However, this vision-dependent sensitivity explained minor individual
      differences in hand-recognition performance. These results indicate that
      nonvisual modalities drive the development of the cortical network underlying the
      recognition of hand gestures with a node in the visual cortex. 

PMID- 25057213
TI  - Curtailing effect of awakening on visual responses of cortical neurons by
      cholinergic activation of inhibitory circuits.
AB  - Visual responsiveness of cortical neurons changes depending on the brain state.
      Neural circuit mechanism underlying this change is unclear. By applying the
      method of in vivo two-photon functional calcium imaging to transgenic rats in
      which GABAergic neurons express fluorescent protein, we analyzed changes in
      visual response properties of cortical neurons when animals became awakened from
      anesthesia. In the awake state, the magnitude and reliability of visual responses
      of GABAergic neurons increased whereas the decay of responses of excitatory
      neurons became faster. To test whether the basal forebrain (BF) cholinergic
      projection is involved in these changes, we analyzed effects of electrical and
      optogenetic activation of BF on visual responses of mouse cortical neurons with
      in vivo imaging and whole-cell recordings. Electrical BF stimulation in
      anesthetized animals induced the same direction of changes in visual responses of
      both groups of neurons as awakening. Optogenetic activation increased the
      frequency of visually evoked action potentials in GABAergic neurons but induced
      the delayed hyperpolarization that ceased the late generation of action
      potentials in excitatory neurons. Pharmacological analysis in slice preparations
      revealed that photoactivation-induced depolarization of layer 1 GABAergic neurons
      was blocked by a nicotinic receptor antagonist, whereas non-fast-spiking layer
      2/3 GABAergic neurons was blocked only by the application of both nicotinic and
      muscarinic receptor antagonists. These results suggest that the effect of
      awakening is mediated mainly through nicotinic activation of layer 1 GABAergic
      neurons and mixed nicotinic/muscarinic activation of layer 2/3 non-fast-spiking
      GABAergic neurons, which together curtails the visual responses of excitatory
      neurons. 

PMID- 25057214
TI  - Liquid helium cryostat with internal fluorescence detection for x-ray absorption
      studies in the 2-6 keV energy region.
AB  - X-ray absorption spectroscop (XAS) in the intermediate x-ray region (2-6 keV) for
      dilute biological samples has been limited because of detector/flux limitations
      and inadequate cryogenic instrumentation. We have designed and constructed a new
      tailpiece/sample chamber for a commercially available liquid helium cooled
      cryostat which overcomes difficulties related to low fluorescence signals by
      using thin window materials and incorporating an internal photodiode detector.
      With the apparatus, XAS data at the Cl, S, and Ca K edges have been collected on
      frozen solutions and biological samples at temperatures down to 60 K. A separate
      chamber has been incorporated for collecting room-temperature spectra of standard
      compounds (for energy calibration purposes) which prevents contamination of the
      cryostat chamber and allows the sample to remain undisturbed, both important
      concerns for studying dilute and radiation-sensitive samples.

PMID- 25057212
TI  - Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification
      in the retina.
AB  - The retina contains two populations of cholinergic amacrine cells, one positioned
      in the ganglion cell layer (GCL) and the other in the inner nuclear layer (INL),
      that together comprise ~1/2 of a percent of all retinal neurons. The present
      study examined the genetic control of cholinergic amacrine cell number and
      distribution between these two layers. The total number of cholinergic amacrine
      cells was quantified in the C57BL/6J and A/J inbred mouse strains, and in 25
      recombinant inbred strains derived from them, and variations in their number and
      ratio (GCL/INL) across these strains were mapped to genomic loci. The total
      cholinergic amacrine cell number was found to vary across the strains, from
      27,000 to 40,000 cells, despite little variation within individual strains. The
      number of cells was always lower within the GCL relative to the INL, and the
      sizes of the two populations were strongly correlated, yet there was variation in
      their ratio between the strains. Approximately 1/3 of that variation in cell
      ratio was mapped to a locus on chromosome 3, where Sex determining region Y box 2
      (Sox2) was identified as a candidate gene due to the presence of a 6-nucleotide
      insertion in the protein-coding sequence in C57BL/6J and because of robust and
      selective expression in cholinergic amacrine cells. Conditionally deleting Sox2
      from the population of nascent cholinergic amacrine cells perturbed the normal
      ratio of cells situated in the GCL versus the INL and induced a bistratifying
      morphology, with dendrites distributed to both ON and OFF strata within the inner
      plexiform layer. 

PMID- 25057215
TI  - A new susceptibility locus for myocardial infarction, hypertension, type 2
      diabetes mellitus, and dyslipidemia on chromosome 12q24.
AB  - We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism
      on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals
      (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence
      detection system. Following adjustment for confounders, the rs2259820_CC (1.19
      (1.01-1.42); P = 0.041), rs2464196_TT (1.19 (1.00-1.40); P = 0.045), and
      rs2259816_T (1.13 (1.01-1.26); P = 0.031) were associated with MI. The
      rs2259820_T (1.14 (1.03-1.26); P = 0.011) and rs2464196_C (1.12 (1.02-1.24); P =
      0.024) were associated with type 2 diabetes mellitus (T2DM), while the
      rs2393791_T (1.14 (1.01-1.28); P = 0.032), rs7310409_G (1.16 (1.03-1.30); P =
      0.013), and rs2464196_AG+GG (1.25 (1.05-1.49); P = 0.012) were implicated in
      hypertension. Hypertriglyceridemia was linked to the rs2393791_T (1.14 (1.02
      1.27); P = 0.018), rs7310409_G (1.12 (1.01-1.25); P = 0.031), rs1169310_G (1.15
      (1.04-1.28); P = 0.010), and rs1169313_CT+TT (1.24 (1.06-1.45); P = 0.008) and
      high low density lipoprotein-cholesterol levels were associated with rs2259820_T
      (1.23 (1.07-1.41); P = 0.004), rs2464196_T (1.22 (1.06-1.39); P = 0.004), and
      rs2259816_T (1.18 (1.02-1.36); P = 0.023). A 7-mer haplotype CATATAC (chi(2) =
      7.50; P = 0.0062), constructed from the studied SNPs, was associated with MI, and
      CATATA implicated in T2DM (chi(2) = 3.94; P = 0.047). Hypertriglyceridemia was
      linked to TGCGGG (chi(2) = 4.26; P = 0.039), and obesity to ACGGGT (chi(2) =
      5.04; P = 0.025). Our results suggest that the HNF1a is a common susceptibility
      gene for MI, T2DM, hypertension, and dyslipidemia.

PMID- 25057216
TI  - Attention deficit hyperactivity disorder: a neglected issue in the developing
      world.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neglected
      illness in a developing country. OBJECTIVES: The objectives of this study are to
      investigate the prevalence and pattern of ADHD among children in a Nigeria.
      METHODS: A structured self-administered questionnaire was used to collect
      information from the parents of children (and older children) who attended
      children outpatients' clinic during the study period. The DSM-IV-TR diagnostic
      criteria for attention deficit hyperactivity disorder were used. RESULTS: Two
      hundred and seventy-three (273) out of 282 questionnaires were filled completely,
      giving a response rate of 96.8%. Nine (9) children fulfilled the stated criteria
      for ADHD giving a prevalence rate of 3.2%. There is no association between gender
      and ADHD (P = 0.784). CONCLUSIONS: The prevalence of ADHD in our setting is 3.2%,
      which is similar to that obtained elsewhere in the world.

PMID- 25057217
TI  - The subcutaneous implantable cardioverter-defibrillator: not for all.

PMID- 25057218
TI  - Repolarization parameters are associated with mortality in chagas disease
      patients in the United States.
AB  - OBJECTIVE: The goal of this study was to examine the association between ECG
      repolarization parameters and mortality in Chagas disease (CD) patients living in
      the United States. METHODS: CD patients with cardiomyopathy (CM) and bundle
      branch block (BBB) or BBB alone were compared to age- and sex-matched controls.
      QT interval, QT dispersion (QTd), T wave peak to T wave end duration (Tp-Te) and
      T wave peak to T wave end dispersion ((Tp-Te)d) were measured. Presence of
      fractionated QRS (fQRS) was also assessed. The main outcome measure was the
      association between ECG parameters and mortality or need for cardiac transplant.
      RESULTS: A total of 18 CM and 13 BBB CD patients were studied with 97%
      originating from Mexico or Central America. QTd (60.0+/-15.0 ms vs 43.5+/-9.8 ms,
      P=0.0002), Tp-Te (102.6+/-29.3 ms vs 77.1+/-11.0 ms, P=0.0002) and (Tp-Te)d
      (39.5+/-9.4 ms vs 22.7+/-7.6 ms, P<0.0001) were prolonged in CD CM patients
      compared to CM controls. Chagas CM patients had more fQRS then controls (84.2+/
      0.10% vs 33.3+/-0.11%, p=0.0005). QTd (59.9+/-15.0 ms vs 29.5+/-6.9 ms, P=0.0001)
      and (Tp-Te)d (40.0+/-15.9 ms vs 18.5+/-5.4 ms, p<0.0001) were longer in the CD
      BBB group compared to BBB controls. Univariate analysis showed QTd (56.9+/-15.0
      ms vs 46.5+/-17.3 ms, p=0.0412) and (Tp-Te)d (36.8+/-13.5 ms vs 28.5+/-13.3 ms,
      p=0.0395) were associated with death and/or need for cardiac transplant.
      CONCLUSION: Our results indicate that P-max and PD are useful
      electrocardiographic markers for identifying the beta-TM-high-risk patients for
      AF onset, even when the cardiac function is conserved.

PMID- 25057219
TI  - Measurement of Left Atrial Pressure is a Good Predictor of Freedom From Atrial
      Fibrillation.
AB  - BACKGROUND: It is suggested that an elevated left atrial pressure (LAP) promotes
      ectopic beats emanating in the pulmonary veins (PVs) and that LAP might be a
      marker for structural remodeling. This study aimed to identify if the
      quantification of LAP correlates with structural changes of the LA and may
      therefore be associated with outcomes following pulmonary vein isolation (PVI).
      METHODS: We analysed data from 120 patients, referred to PVI due to drug
      refractory atrial fibrillation (AF) (age 63+/-8; 57% men). The maximum (mLAP) and
      mean LAP (meLAP) were measured after transseptal puncture. RESULTS AND
      CONCLUSIONS: Within a mean follow-up of 303+/-95 days, 60% of the patients
      maintained in sinus rhythm after the initial procedure and 78% after repeated
      PVI. Performing univariate Cox-regression analysis, type of AF, LA-volume (LAV),
      mLAP and the meLAP were significant predictors of recurrence after PVI (p=0.03;
      p=0.001; p=0.01). In multivariate analysis mLAP>18mmHg, LAV>100 ml and the
      presence of persistent AF were significant predictors (p=0.001; p=0.019;
      p=0.017). The mLAP >18 mmHg was associated with a hazard ratio of 3.8. Analyzing
      receiver-operator characteristics, the area under the curve for mLAP was 0.75
      (p<0.01). mLAP >18 mmHg predicts recurrence with a sensitivity of 77 % and
      specificity of 60 %. There was a linear correlation between the LAV from MDCT and
      mLAP (p = 0.01, R2 = 0.61). The mLAP measured invasively displays a significant
      predictor for AF recurrence after PVI. There is a good correlation between LAP
      and LAV and both factors may be useful to quantify LA remodeling.

PMID- 25057220
TI  - Pulmonary vein compression after implantation of a left atrial appendage
      occluder: presentation and discussion of a case.

PMID- 25057221
TI  - Epicardial ablation of focal atrial tachycardia arising from left atrial
      appendage in children.
AB  - Focal left atrial tachycardia (FLAT) although a common cause of supraventricular
      tachycardia(SVT) among children, the one's arising from left atrial appendage
      (LAA) present a unique challenge for successful ablation because of anatomical
      location. We present two children with FLAT arising from the epicardial LAA,
      successfully mapped and ablated through percutaneuous epicardial approach. 

PMID- 25057222
TI  - Ischemic ventricular tachycardia presenting as a narrow complex tachycardia.
AB  - This report describes a patient presenting with a narrow complex tachycardia in
      the context of prior myocardial infarction and impaired ventricular function.
      Electrophysiological studies confirmed ventricular tachycardia and activation and
      entrainment mapping demonstrated a critical isthmus within an area of scar
      involving the His-Purkinje system accounting for the narrow QRS morphology. This
      very rare case shares some similarities with upper septal ventricular tachycardia
      seen in patients with structurally normal hearts, but to our knowledge has not
      been seen previously in patients with ischemic heart disease. 

PMID- 25057223
TI  - Parasystole in a mahaim accessory pathway.
AB  - Hypertrophic cardiomyopathy's (HCM) association with sudden cardiac death is well
      recognised. The risk of sudden cardiac death is known to increase when there is a
      history of unexplained syncope, abnormal blood pressure response during exercise,
      severe left ventricular hypertrophy or a family history of unexplained death.
      Implantable Cardioverter Defibrillator (ICD) implantation has been widely used
      for primary and secondary prevention of sudden cardiac death (SCD) in people with
      HCM. Subcutaneous ICD (S-ICD) therapy has been developed to overcome some of the
      problems associated with the transvenous leads used in conventional ICDs. In this
      article, we report the use of S-ICD in a patient with HCM and multiple risk
      factors for sudden cardiac death, this device had to be extracted due to
      recurrent inappropriate shocks caused by over sensing of atrial flutter and
      failure to treat a VT episode. We are not aware of any reports of inappropriate
      shocks caused by atrial flutter in people with a S-ICD. 

PMID- 25057224
TI  - Intermittent Right Ventricular Outflow Tract Capture due to Chronic Right Atrial
      Lead Dislodgement.
AB  - A 58 year old male, known case of type 2 diabetes and hypertension, had undergone
      implantation of a dual chamber pacemaker(DDDR) in 2007 for complaints of
      recurrent syncope and trifascicular block with a normal ejection fraction
      andnormal coronaries. His post implantation parameters were normal at that
      time.He now presented to our pacemaker clinic where his ECG done showed two types
      o fpaced complexes. The first few complexes were consistent with atrial sensed
      right ventricular apical pacing with left superior axis. Later complexes showed
      loss of atrial sensing with pacing from right ventricular outflow tract(inferior
      axis) with subtle oscillation in it's axis. On application of magnet, two
      pacemaker spikes were visible withinterspike interval of 120 ms and paced
      complexes with inferior axis starting from the first spike suggesting that the
      atrial lead was responsible for RVOT depolarization. On interrogation of the
      pacemaker, atrial EGM showed sensed activity from atrium followed by large sensed
      ventricular complex. Fluoroscopy confirmed that the atrial lead was dislodged and
      was intermittently prolapsing into the RVOT. Since the patient was asymptomatic,
      he refused any intervention and subsequentlyhis atrial lead was switched off by
      telemetry. The above case signifies that asymptomatic lead dislodgement is no
      talways manifested as loss of capture and even subtle variation of the axis o
      fthe paced complexes can provide us with a clue that can be confirmed by
      telemetry of the pacemaker and fluoroscopy. 

PMID- 25057225
TI  - Parasystole in a mahaim accessory pathway.
AB  - Automaticity has been described in Mahaim pathways, both spontaneously and during
      radiofrequency ablation. We describe an unusual case of automatic rhythm from a
      Mahaim pathway presenting as parasystole. The parasystolic beats were also found
      to initiate tachycardia, resulting in initial presentation with incessant
      tachycardia and tachycardia induced cardiomyopathy. 

PMID- 25057226
TI  - Effect of gastric acid suppressants and prokinetics on peritoneal dialysis
      related peritonitis.
AB  - AIM: To investigate the effect of gastric acid suppressants and prokinetics on
      peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a
      single-center, retrospective study. The medical records of 398 PD patients were
      collected from January 2000 to September 2012 and analyzed to compare patients
      with at least one episode of peritonitis (peritonitis group, group A) to patients
      who never had peritonitis (no peritonitis group, group B). All peritonitis
      episodes were analyzed to compare peritonitis caused by enteric organisms and
      peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who
      met the inclusion criteria, 61 patients had at least one episode of peritonitis
      and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%)
      in group A and 15 of 59 patients (25.4%) in group B used gastric acid
      suppressants. Only the use of H2-blocker (H2B) was associated with an increased
      risk of PD-related peritonitis; the use of proton pump inhibitors, other
      antacids, and prokinetics was not found to be a significant risk factor for PD
      related peritonitis. A total of 81 episodes of peritonitis were divided into
      enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative
      organism, and gastric acid suppressants and prokinetics did not increase the risk
      of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased
      risk of overall PD-related peritonitis, although further studies are required to
      clarify the effects of drugs on PD-related peritonitis.

PMID- 25057227
TI  - Knowledge, attitudes, and experience of dentists living in Saudi Arabia toward
      child abuse and neglect.
AB  - AIM: To analyze the experience and knowledge of dental practitioners in Saudi
      Arabia regarding the identification of child abuse and neglect (CAN), to identify
      barriers that prevent the reporting of suspected cases of child maltreatment by
      dental practitioners, and to assess the need for training dentists in child
      protection. METHODS: A self-administered, web-based questionnaire was emailed to
      all of the members of the Saudi Dental Society (n = 7352) in 2012. RESULTS: The
      respondents (n = 122) demonstrated good knowledge of the forms and indicators of
      CAN. Moreover, a large proportion (59%) had experienced a case of child abuse or
      neglect in their practice over the previous five years. However, only about 10%
      of these respondents made a report. Fear of family reprisal, lack of certainty
      about the diagnosis of child maltreatment, and uncertainty about case management
      were critical barriers to the reporting of the suspected child maltreatment. In
      addition, only 20.9% of the respondents reported having knowledge of a child
      protection policy in their workplace. CONCLUSIONS: Based on the results of this
      survey, it appears that the level of knowledge among the respondents regarding
      the forms and indicators of CAN is good. However, a large proportion of
      respondents did not take action regarding suspected cases of CAN in their
      practice over the past five years. Therefore, additional resources and training
      are needed to support the identification and management of cases of child
      maltreatment by dental practitioners.

PMID- 25057228
TI  - Smoking among dental students at King Saud University: Consumption patterns and
      risk factors.
AB  - OBJECTIVE: To assess smoking prevalence among dental students at King Saud
      University (KSU) and to determine possible risk factors of tobacco use. METHODS:
      A self-addressed invitation letter was sent to all dental students (males and
      females) at KSU requesting participation in this study. Data on smoking habits,
      associated risk factors, and demographic factors, such as age, marital status,
      residency status, the student's year of study, and grade point average, were
      collected by an electronic self-administered questionnaire sent via email. Data
      were analyzed using SPSS. Significant differences between different groups were
      assessed with a Pearson Chi-Square test at alpha = 0.05. Logistic regression
      analysis was used to calculate the odds ratio (OR) and 95% confidence interval
      (95% CI) and to determine the effect of different risk factors on students'
      smoking habits. RESULTS: Of the 600 registered dental students, 400 students
      responded (230 males, 170 females), representing a response rate of 67%. More
      male than female students were current smokers (27.6% vs. 2.4%, p < 0.001). Most
      smokers used shisha tobacco only (N = 35, 51.5%), followed by both shisha tobacco
      and cigarettes (N = 17, 25%), or cigarettes only (N = 16, 23.5%). Male students
      were about 4 times more likely to be smokers if all or most of their friends were
      smokers compared to students who had some friends who smoked (OR = 3.9, 95% CI =
      1.9-7.7). A high proportion of current smokers (47.8%) reported stress as the
      main reason for smoking. Twenty-six percent of dental students (N = 87) who are
      currently nonsmokers reported that they have used tobacco at some point in their
      lives. Over two thirds of sampled students (63%) believed that public tobacco
      usage is not well addressed in the current college curriculum. CONCLUSION:
      Approximately one in every four male dental students at KSU is a smoker. Having
      friends who are smokers was the most important risk factor associated with
      smoking. There is a general belief among dental students that public tobacco use
      is not well addressed in the dental college curriculum.

PMID- 25057229
TI  - Attitude and awareness of dentist towards resin bonded bridges in Saudi Arabia.
AB  - STATEMENT OF THE PROBLEM: Resin bonded bridges (RBBs) offer a conservative
      approach to tooth replacement. However, the use of this treatment option has been
      limited. Therefore, the aim of this study was to assess the knowledge and
      attitude of dentists in Saudi Arabia, including general dental practitioners
      (GDPs) and prosthodontic and restorative specialists (SPs), toward RBBs. METHODS:
      In this cross-sectional study, questionnaires designed to survey knowledge of RBB
      performance factors were distributed to GDPs and SPs (n = 400). Specifically,
      opinions of GDPs and SPs regarding clinical, mechanical, technique- and patient
      dependent performance factors of RBBs were obtained. Average significance and Chi
      square tests were used to identify the frequency, pattern, and significance of
      the response variables identified. RESULTS: A majority (65.3%) of the subjects
      reported using RBBs in less than 10% of their prosthodontic cases. The most
      common reason for the limited clinical application of RBBs was perceived poor
      retention (23.45%). In addition, SPs regarded the influence of enamel structure,
      number of pontics, cement type, RBB design, and surface treatment as "very
      significant" factors with respect to RBB survival. Overall, a statistically
      significant difference was observed between the responses of GDPs and SPs
      regarding their knowledge of performance factors for RBBs. CONCLUSION: In
      comparison to SPs, GDPs reported greater disagreement with current standards for
      RBB success factors. Moreover, 60% of SPs and 71% of GDPs used RBBs for less than
      10% of their prosthodontic cases. Therefore, continuing education opportunities
      are needed for practicing dentists, and undergraduate students need to receive
      greater exposure to the clinical application of RBBs.

PMID- 25057230
TI  - Pre-operative assessment of relationship between inferior dental nerve canal and
      mandibular impacted third molar in Saudi population.
AB  - OBJECTIVE: To study the correlation between the position of the inferior dental
      (ID) nerve canal and the angulation of impacted mandibular third molars using
      dental cone beam computed tomography (CBCT). MATERIALS AND METHODS: The study
      considered 100 impactions in 85 patients (60 males, 25 females), for whom an
      initial panoramic radiographic assessment had revealed that the ID canal and the
      lower 3rd molar were in close proximity. A CBCT scan of each patient was carried
      out to assess how the ID nerve canal position influenced the class and position
      of impaction, angulation of impaction, and bone contact. RESULTS: Class I
      position B impactions were found in the majority of cases, where the position of
      the ID canal was approximate to the lingual plate and inferior to the 3rd molar
      (85.7%). The results were statistically significant (p = 0.001). 96% of the ID
      canals showed bone contact. Of these, 77.1% of ID canals exhibited lingual bone
      contact, inferior to impaction. The results were statistically significant (p =
      0.001). Horizontally angulated impactions were most common in the mandible, and
      significantly associated with lingual and inferior positioning of the ID canal
      (76.2%). CONCLUSIONS: Our sample population most commonly exhibited horizontally
      angulated class I position B impactions of the mandible. The position of the ID
      canal significantly influenced the type of impaction and bone contact.

PMID- 25057231
TI  - Effect of honey in preventing gingivitis and dental caries in patients undergoing
      orthodontic treatment.
AB  - OBJECTIVES: THIS STUDY WAS CONDUCTED TO INVESTIGATE THE FOLLOWING: (1) the
      effects of chewing honey on plaque formation in orthodontic patients, (2) the
      effect of chewing honey on dental plaque bacterial counts, (3) determine if honey
      possesses antibacterial effects on bacteria recovered from plaques. METHODS:
      Female orthodontic patients (n = 20, 12-18 years of age) participated in this
      randomized controlled study. The effects of honey were compared to treatment with
      either 10% sucrose or 10% sorbitol that served as positive and negative controls,
      respectively. The pH of plaque was measured using a digital pH meter prior to
      baseline and at 2, 5, 10, 20, and 30 min after chewing honey or rinsing with
      control solutions and the numbers of Streptococcus mutans, Lactobacilli, and
      Prophymonas gingivalis in respective plaques were determined. The antibacterial
      activity of honey was tested against commonly used antibiotics using the disk
      diffusion method. RESULTS: Significant differences in pH were observed in the
      honey and sucrose groups compared to the pH observed in the sorbitol group (p ?
      0.001). The maximum pH drop occurred at 5 min in both the honey and sucrose
      groups; however the pH in the honey group rapidly recovered 10-20 min after
      exposure and did not drop below the critical decalcification pH of 5.5. On the
      other hand, the pH following sucrose exposure fell <5.5 and was associated with a
      30 min recovery time. The pH observed for the sorbitol group did not change over
      time. Bacterial counts were significantly reduced in the honey group compared to
      the other treatment groups (p ? 0.001) and honey significantly inhibited the
      growth of all studied strains compared to inhibition observed with antibiotics (p
      ? 0.001). CONCLUSIONS: Honey can be used as an alternative to traditional
      remedies for the prevention of dental caries and gingivitis following orthodontic
      treatment.

PMID- 25057232
TI  - Prevalence of dental caries among 12-14 year old children in Qatar.
AB  - BACKGROUND: To ensure the oral health of a population, clinicians must deliver
      appropriate dental services, and local communities need to have access to dental
      care facilities. However, establishment of this infrastructure must be based on
      reliable information regarding disease prevalence and severity in the target
      population. OBJECTIVES: The aims of this study were to measure the incidence of
      dental caries in school children aged 12-14 throughout Qatar, including the
      influence of socio-demographic factors. MATERIALS AND METHODS: A cross-sectional
      study was conducted in Qatar from October 2011 to March 2012. A total of 2113
      children aged 12-14 were randomly selected from 16 schools located in different
      geographic areas. Three calibrated examiners using World Health Organization
      (WHO) criteria to diagnose dental caries performed the clinical examinations.
      Data analyses were subsequently conducted. RESULTS: The mean decayed, missing,
      and filled teeth index values were respectively 4.62 (+/-3.2), 4.79 (+/-3.5), and
      5.5 (+/-3.7), for 12, 13, and 14 year-old subjects. Caries prevalence was 85%.
      The mandibular incisors and canines were least affected by dental caries, while
      maxillary and mandibular molars exhibited the highest incidence of dental caries.
      Dental caries were affected by socio-demographic factors; significant differences
      were detected between female and male children, where more female children showed
      dental caries than male children. In addition, children residing in semi-urban
      areas showed more dental caries than in urban areas. CONCLUSION: Results
      indicated that dental caries prevalence among school children in Qatar has
      reached critical levels, and is influenced by socio-demographic factors. The mean
      decayed, missing, and filled teeth values obtained in this study were the second
      highest detected in the Eastern Mediterranean region.

PMID- 25057233
TI  - Papillon-Lefevre syndrome: Reporting consanguinity as a risk factor.
AB  - Papillon-Lefevre syndrome (PLS) is an autosomal recessive genetic disorder
      characterized by palmoplantar hyperkeratosis associated with severe early-onset
      periodontitis and premature loss of primary and permanent teeth. This report
      describes two cases of PLS in 28-year-old female and 16-year-old male siblings
      with consanguineously married parents. The patients presented to the Department
      of Public Health Dentistry of a dental education and research institute in India
      with thickening, flaking, and scaling of the skin on the palms and soles of the
      feet. On oral examination, the female patient presented completely resorbed
      maxillary and mandibular alveolar ridges with retention of only the third molars.
      The male patient retained only teeth 18, 13, 28, 38, and 45. Based on complete
      histories and clinical examination findings, a final diagnosis of PLS was made
      and treatment was initiated using an interdisciplinary dental approach in both
      cases. 

PMID- 25057234
TI  - The effect of laterally positioned flap-revised technique and 24%
      ethylenediaminetetraacetic acid root conditioning on root coverage: A case
      report.
AB  - Complete root coverage is considered the true goal of treatment of gingival
      recession defects because only complete coverage assures recovery from the
      hypersensitivity and esthetic defects associated with recession areas. Previous
      studies have shown that the laterally positioned flap (LPF) technique or root
      surface biomodification yields a higher percentage of complete root coverage upon
      gingival recession treatment. This article highlights the use of the laterally
      positioned pedicle flap-revised technique (LPFRT) as a modification of the LPF
      technique, along with 24% EDTA gel as a root surface biomodification agent, in
      the management of localized gingival recession defects. Clinical examination
      revealed a Miller class II recession defect on the buccal aspect of the lower
      right central incisor, as well as the presence of aberrant frenum pull adjacent
      to the recession defect. The LPFRT, together with 24% EDTA gel, was speculated to
      cover the gingival recession defect. The frenectomy, along with periosteal
      fenestration, was planned simultaneously with LPFRT. After 6 months of therapy,
      the clinical condition was stable with complete root coverage and satisfactory
      healing of the gingival tissues at both the donor and recipient sites with no
      signs of inflammation. 

PMID- 25057235
TI  - Negotiating Emotional Support: Sober Gay Latinos and their Families.
AB  - This study explores how sober gay Latino men obtain support from their families.
      Familial ties can be a protective health factor, yet many gay Latinos experience
      rejection from family members because of their sexuality. There are very few
      studies that examine the extent and quality of emotional support from kin for
      this population. Understanding family dynamics within the context of recovery and
      sexuality can increase our understanding of how to leverage family ties to
      develop alcohol abuse interventions. The study was conducted semi-structured
      interviews with 30 sober gay Latinos using a grounded theory approach. Analyses
      of the qualitative data identified the following themes: Family values shaped the
      participants' perception of their range of choices and emotional responses;
      participants reported feeling loved and supported even when sexuality was not
      discussed with parents; and family support for sobriety is essential. Findings
      suggest that familial ties shape perceptions of support and importance of
      disclosing sexual identity. Family support often results from agreements about
      sexual identity disclosure, and some families can overcome cultural and religious
      taboos on sexuality. Future studies should investigate families that negotiate
      acceptance with their gay members, and whether they exhibit heterosexual biases
      that may influence the psychological stress of gay Latino men who wish to be
      sober.

PMID- 25057236
TI  - Influence of modularity and regularity on disparity of atelostomata sea urchins.
AB  - A modularity approach is used to study disparity rates and evolvability of sea
      urchins belonging to the Atelostomata superorder. For this purpose, the
      pentameric sea urchin architecture is partitioned into modular spatial components
      and the interference between modules is quantified using areas and a measurement
      of the regularity of the spatial partitions. This information is used to account
      for the variability through time (disparity) and potential for morphological
      variation and evolution (evolvability) in holasteroid echinoids. We obtain that
      regular partitions of the space produce modules with high modular integrity,
      whereas irregular partitions produce low modular integrity; the former ones are
      related with high morphological disparity (facilitation hypothesis). Our analysis
      also suggests that a pentameric body plan with low regularity rates in
      Atelostomata reflects a stronger modular integration among modules than within
      modules, which could favors bilaterality against radial symmetry. Our approach
      constitutes a theoretical platform to define and quantify spatial organization in
      partitions of the space that can be related to modules in a morphological
      analysis. 

PMID- 25057237
TI  - Integrative genomic analysis for the discovery of biomarkers in prostate cancer.
AB  - Genome-wide association studies (GWAS) have achieved great success in identifying
      single nucleotide polymorphisms (SNPs, herein called genetic variants) and genes
      associated with risk of developing prostate cancer. However, GWAS do not
      typically link the genetic variants to the disease state or inform the broader
      context in which the genetic variants operate. Here, we present a novel
      integrative genomics approach that combines GWAS information with gene expression
      data to infer the causal association between gene expression and the disease and
      to identify the network states and biological pathways enriched for genetic
      variants. We identified gene regulatory networks and biological pathways enriched
      for genetic variants, including the prostate cancer, IGF-1, JAK2, androgen, and
      prolactin signaling pathways. The integration of GWAS information with gene
      expression data provides insights about the broader context in which genetic
      variants associated with an increased risk of developing prostate cancer operate.

PMID- 25057238
TI  - DNA Methylation at the Novel CpG Sites in the Promoter of MED15/PCQAP Gene as a
      Biomarker for Head and Neck Cancers.
AB  - Head and neck cancers (HNCs) represent a significant and ever-growing burden to
      the modern society, mainly due to the lack of early diagnostic methods. A
      significant number of HNCs is often associated with drinking, smoking, chewing
      beetle nut, and human papilloma virus (HPV) infections. We have analyzed DNA
      methylation patterns in tumor and normal tissue samples collected from head and
      neck squamous cell carcinoma (HNSCC) patients who were smokers. We have
      identified novel methylation sites in the promoter of the mediator complex
      subunit 15 (MED15/PCQAP) gene (encoing a co-factor important for regulation of
      transcription initiation for promoters of many genes), hypermethylated
      specifically in tumor cells. Two clusters of CpG dinucleotides methylated in
      tumors, but not in normal tissue from the same patients, were identified. These
      CpG methylation events in saliva samples were further validated in a separate
      cohort of HNSCC patients (who developed cancer due to smoking or HPV infections)
      and healthy controls using methylation-specific PCR (MSP). We used saliva as a
      biological medium because of its non-invasive nature, close proximity to the
      tumors, easiness and it is an economically viable option for large-scale
      screening studies. The methylation levels for the two identified CpG clusters
      were significantly different between the saliva samples collected from healthy
      controls and HNSCC individuals (Welch's t-test returning P < 0.05 and Mann
      Whitney test P < 0.01 for both). The developed MSP assays also provided a good
      discriminative ability with AUC values of 0.70 (P < 0.01) and 0.63 (P < 0.05).
      The identified novel CpG methylation sites may serve as potential non-invasive
      biomarkers for detecting HNSCC. 

PMID- 25057239
TI  - Preliminary development of a fiber optic sensor for measuring bilirubin.
AB  - Preliminary development of a fiber optic bilirubin sensor is described, where an
      unclad sensing portion is used to provide evanescent wave interaction of the
      transmitted light with the chemical environment. By using a wavelength
      corresponding to a bilirubin absorption peak, the Beer-Lambert Law can be used to
      relate the concentration of bilirubin surrounding the sensing portion to the
      amount of absorbed light. Initial testing in vitro suggests that the sensor
      response is consistent with the results of bulk absorption measurements as well
      as the Beer-Lambert Law. In addition, it is found that conjugated and
      unconjugated bilirubin have different peak absorption wavelengths, so that two
      optical frequencies may potentially be used to measure both types of bilirubin.
      Future development of this device could provide a means of real-time, point-of
      care monitoring of intravenous bilirubin in critical care neonates with
      hyperbilirubinemia. 

PMID- 25057240
TI  - Eastern Carolina Asthma Prevention Program (ECAPP): An Environmental Intervention
      Study Among Rural and Underserved Children with Asthma in Eastern North Carolina.
AB  - OBJECTIVE: Asthma is the most common chronic childhood condition affecting 6.3
      million (US) children aged less than 18 years. Home-based, multi-component,
      environmental intervention studies among children with asthma have demonstrated
      to be effective in reducing asthma symptoms. In this study, a local hospital and
      university developed an environmental intervention research pilot project,
      Eastern Carolina Asthma Prevention Program (ECAPP), to evaluate self-reported
      asthma symptoms, breathing measurements, and number of asthma-related emergency
      department (ED) visits among low-income, minority children with asthma living in
      rural, eastern North Carolina. Our goal was to develop a conceptual model and
      demonstrate any asthma respiratory improvements in children associated with our
      home-based, environmental intervention. METHODS: This project used a single
      cohort, intervention design approach to compare self-reported asthma-related
      symptoms, breathing tests, and ED visits over a 6 month period between children
      with asthma in an intervention study group (n = 12) and children with asthma in a
      control study group (n = 7). The intervention study group received intense asthma
      education, three home visits, 2 week follow-up telephone calls, and environmental
      intervention products for reducing asthma triggers in the home. The control group
      received education at baseline and 2 week calls, but no intervention products.
      RESULTS: At the end of the study period, significant improvements were observed
      in the intervention group compared with the control group. Overall, the
      intervention group experienced a 58% (46 +/- SD 26.9) reduction in self-reported
      asthma symptoms; 76% (34 +/- SD 29.7) decrease in rescue medicine; 12% (145 +/-
      SD 11.3) increase in controller medicine; 37% decrease in mean exhaled nitric
      oxide levels and 33% fewer ED asthma-related visits. CONCLUSION: As demonstrated,
      a combination of efforts appeared effective for improving asthma respiratory
      symptoms among children in the intervention group. ECAPP is a low cost pilot
      project that could readily be adapted and expanded into other communities
      throughout eastern North Carolina. Future efforts could include enhanced
      partnerships between environmental health professionals at local health
      departments and pediatric asthma programs at hospitals to carry out ECAPP.

PMID- 25057242
TI  - Blood pressure control and exaggerated blood pressure response in nigerians with
      essential hypertension.
AB  - BACKGROUND: Blood pressure (BP) control in hypertensives is important in
      preventing cardiovascular (CV) morbidity and mortality. This work was done to
      assess control of BP among Nigerian hypertensives at rest and during exercise.
      MATERIALS AND METHODS: A total of 85 male hypertensives were recruited
      consecutively and had clinical evaluation and treadmill (TM) exercise testing
      using the Bruce protocol. Independent t-test, chi-square, and Fisher's exact
      tests were used to compare patients with controlled and uncontrolled BP using
      SPSS version 16 software. Adjustment for confounders was by logistic regression
      and general linear model. RESULTS: Resting systolic BP (rSBP) (mmHg) and resting
      diastolic BP (rDBP) (mmHg) were significantly lower in the controlled group
      (115.0 +/- 12.29, 133.1 +/- 12.27, P = <0.001 and 76.00 +/- 6.55, 91.4 +/- 8.00,
      P = <0.001). The proportion of subjects with controlled BP was 37.7%. Adjusted
      peak SBP (PSBP) during exercise (mmHg) was significantly higher in the
      uncontrolled than in the controlled group (210.5 +/- 27.31, 191.8 +/- 20.77, P =
      0.001). Adjusted exaggerated blood pressure response (EBPR) was found in 37
      subjects (44%) in the uncontrolled group while seven subjects (0.1%) had EBPR in
      the controlled group (P = 0.003). CONCLUSION: This study shows that EBPR is
      significantly higher in subjects with uncontrolled BP compared with those with
      controlled BP. Therefore, good BP control may be the key factor in preventing
      EBPR in hypertensives.

PMID- 25057243
TI  - Bilateral carotid paraganglioma: surgery and radiotherapy.
AB  - BACKGROUND: Paragangliomas are relatively rare vascular tumors that develop from
      the neural crest cells of carotid bifurcation. They usually present as slow
      growing, painless unilateral neck masses; bilateral presentation is rare and is
      mostly associated with familial forms. Bilateral total resection is not always
      possible for high-grade bilateral tumors, and radiotherapy is a good alternative,
      with cure rates similar to surgery. CASE REPORT: A 35-year-old female patient was
      admitted with a chief complaint of a bilateral, painless mass located on her
      neck. Subsequent magnetic resonance imaging (MRI) and angiographic imaging
      revealed bilateral hypervascular masses surrounding her carotid at 360 degrees ,
      and they were interpreted as stage 3 carotid paragangliomas according to the
      Shamblin classification protocol. Surgery was carried out on the left carotid
      paraganglioma and the mass was totally resected. It was thought that the patient
      could not tolerate bilateral surgery. Primary radiotherapy was planned on the
      right carotid paraganglioma: 59.8 gray (Gy) conformal, Linac-based multileaf
      collimator radiotherapy with a 180 cGy daily dosage, and five fractions per week
      were planned. RESULTS: Follow-up at 3 months following the conclusion of
      radiotherapy revealed no significant regression. A follow-up MRI 6 months and 24
      months later revealed 59% regression. Grade 2 esophagitis and minimal neck edema
      were the only complications noted during the course of radiotherapy and during
      the 24-month follow-up period. No complications or relapse were observed except
      for edema following neck surgery.

PMID- 25057241
TI  - Biomarkers of HIV-associated Cancer.
AB  - Cancer biomarkers have provided great opportunities for improving the management
      of cancer patients by enhancing the efficiency of early detection, diagnosis, and
      efficacy of treatment. Every cell type has a unique molecular signature, referred
      to as biomarkers, which are identifiable characteristics such as levels or
      activities of a myriad of genes, proteins, or other molecular features.
      Biomarkers can facilitate the molecular definition of cancer, provide information
      about the course of cancer, and predict response to chemotherapy. They offer the
      hope of early detection as well as tracking disease progression and recurrence.
      Current progress in the characterization of molecular genetics of HIV-associated
      cancers may form the basis for improved patient stratification and future
      targeted or individualized therapies. Biomarker use for cancer staging and
      personalization of therapy at the time of diagnosis could improve patient care.
      This review focuses on the relevance of biomarkers in the most common HIV
      associated malignancies, namely, Kaposi sarcoma, non-Hodgkin's lymphoma, and
      invasive cervical cancer. 

PMID- 25057244
TI  - Laser Posterior Cordotomy: Is it a Good Choice in Treating Bilateral Vocal Fold
      Abductor Paralysis?
AB  - BACKGROUND: Bilateral abductor vocal fold paralysis can lead to respiratory
      distress and dyspnea. OBJECTIVES: To assess the efficacy of CO2 laser unilateral
      posterior cordotomy in cases with bilateral abductor paralysis as regards
      improvement of dyspnea with preservation of satisfactory voice and swallowing
      after the operation. METHODS: A prospective study was done on 18 patients with
      bilateral abductor vocal fold paralysis (10 females and 8 males) from November
      2010 to December 2012 with their ages ranging from 32 to 64 years. RESULTS: All
      patients showed improvement of dyspnea after the operation, most of the patients
      suffered from mild to moderate dyspnea in the immediate post-operative period,
      and two patients needed another intervention to solve it. All the patients had
      satisfactory results of their voice after the operation, and one patient only
      suffered from temporary aspiration. CONCLUSION: Unilateral CO2 laser posterior
      cordotomy is an easy and effective procedure to solve the dyspnea after bilateral
      vocal fold abductor paralysis without aspiration or significant voice alteration.

PMID- 25057245
TI  - The Prognostic Role of the Neutrophil-to-Lymphocyte Ratio in Oropharyngeal
      Carcinoma Treated with Chemoradiotherapy.
AB  - BACKGROUND: The aim of the study is to investigate the prognostic role of pre
      treatment of markers of the systemic inflammatory response (neutrophil-to
      lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin) in
      patients with oropharyngeal carcinoma treated with chemoradiotherapy. METHODS: A
      total of 251 patients with oropharyngeal squamous cell cancer treated with
      chemoradiotherapy between 2004 and 2010 were retrospectively identified. NLR,
      PLR, and albumin were recorded from baseline blood parameters. NLR threshold of
      >5 and PLR thresholds of <=150, >150 and <=300, and >300 were used for analysis.
      RESULTS: Median follow-up was 46 months (range 9-98). The 3 year overall
      survival, local control, regional control, and distant control were 70%, 85%,
      87%, and 87%, respectively. On multivariate analysis, locoregional control was
      associated with T stage (HR 3.3 (95% CI 1.5-6.9), P = 0.002) and NLR (HR 2.1 (95%
      CI 1.1-3.9), P = 0.023). Overall survival was associated with T stage (HR 2.47
      (95% CI 1.45-4.2), P = 0.001) and grade (HR 0.61 (95% CI 0.38-0.99), P = 0.048).
      PLR and albumin were not significantly associated with disease outcomes or
      survival. CONCLUSIONS: The NLR is an independent prognostic factor for
      locoregional control in oropharyngeal cancer treated with chemoradiotherapy.

PMID- 25057247
TI  - Redescription of Platynaspisflavoguttata (Gorham) (Coleoptera, Coccinellidae) and
      notes on nomenclature of Platynaspiskapuri Chakraborty & Biswas.
AB  - Platynaspisflavoguttata (Gorham) (Coleoptera: Coccinellidae) is redescribed and
      the male genitalia are illustrated for the first time. It is also recorded from
      Sri Lanka for the first time. Platynaspisbimaculata (Hoang, 1983) is a new junior
      synonym of Platynaspisbimaculata Pang & Mao, 1979 (new synonym).
      Platynaspiskapuri Chakraborty & Biswas, 2000, the replacement name for
      Platynaspisbimaculata Pang & Mao, 1979 established by Ukrainsky (2007), is also
      the new replacement name for Platynaspisbimaculata (Hoang, 1983), as both are
      junior homonyms of Platynaspisbimaculata Weise, 1888 besides being synonyms.
      Platynaspishoangi Ukrainsky (2007) is an unnecessary replacement name for
      Platynaspisbimaculata (Hoang). 

PMID- 25057246
TI  - Beyond information retrieval and electronic health record use: competencies in
      clinical informatics for medical education.
AB  - Physicians in the 21st century will increasingly interact in diverse ways with
      information systems, requiring competence in many aspects of clinical
      informatics. In recent years, many medical school curricula have added content in
      information retrieval (search) and basic use of the electronic health record.
      However, this omits the growing number of other ways that physicians are
      interacting with information that includes activities such as clinical decision
      support, quality measurement and improvement, personal health records,
      telemedicine, and personalized medicine. We describe a process whereby six
      faculty members representing different perspectives came together to define
      competencies in clinical informatics for a curriculum transformation process
      occurring at Oregon Health & Science University. From the broad competencies, we
      also developed specific learning objectives and milestones, an implementation
      schedule, and mapping to general competency domains. We present our work to
      encourage debate and refinement as well as facilitate evaluation in this area. 

PMID- 25057248
TI  - Guide to the vascular flora of the savannas and flatwoods of shaken creek
      preserve and vicinity (pender & onslow counties, north Carolina, u.s.a.).
AB  - Shaken Creek Preserve ("SCP") is a 2,448 ha (6,050 ac) natural area in Pender and
      Onslow Counties, North Carolina (U.S.A). Best known for its high-quality longleaf
      pine savanna habitat, the site contains seven savanna or savanna-like plant
      community types (i.e., flatwoods or sandhills), three of which are globally
      critically imperiled (G1): Sandy Pine Savanna (Rush Featherling subtype), Wet
      Loamy Pine Savanna, and Very Wet Loamy Pine Savanna. SCP hosts three Federally
      Endangered plant species and six Federal Species of Concern. Formerly a private
      hunting club, the site was virtually unknown to scientists until the 1990s;
      consequently, few biological inventories of SCP have been conducted. In
      particular, no systematic floristic inventories of the species-rich savannas have
      been undertaken, despite the fact that floristic data is critical to the
      effective management of any natural area. The goals of this study were to (1)
      inventory the vascular flora of the savannas, flatwoods, and sandhill community
      types on site through the collection of voucher specimens; (2) provide a
      comprehensive checklist of the flora based on collections and reports made from
      the site and from the same or similar habitats in the vicinity (i.e., within 2
      miles of SCP); and (3) create an illustrated guide based on the checklist. In
      order to increase the usefulness of the guide, taxa not currently known from SCP
      but collected or reported from the same or similar habitats within two miles of
      SCP, are included in the guide. Eighty-three families containing 450 taxa,
      including thirty-two Significantly Rare and thirty-eight Watch List taxa, were
      collected or reported from SCP; an additional seven families containing a total
      of 102 taxa, including eighteen Significantly Rare and seven Watch List taxa,
      were collected or reported from the vicinity. In total, ninety families
      containing 552 taxa, including fifty Significantly Rare and forty-five Watch List
      taxa, are treated in the guide. Dichotomous keys are provided to all vouchered or
      reported families, genera, and species. The following features are provided for
      all species and infraspecific taxa: flowering and fruiting phenology; synonymy
      with Manual of the Vascular Flora of the Carolinas, the Flora of North America,
      and Flora of the Southern and Mid-Atlantic States; relevant voucher information;
      and, for most taxa, line drawings and/or photographs. For taxa collected from
      SCP, community types in which the taxa occur and estimates of abundance on site
      are also provided. 

PMID- 25057249
TI  - The distribution of the vascular plants on the North Frisian Island, Amrum.
AB  - Amrum is a small barrier island on the north-west coast of Germany. The
      distribution of vascular plants was examined by surveying their 1km(2) grid
      square occupancy across the whole island. These data were used in a study on the
      recent vegetation change in the island. These data include 3786 observations of
      450 taxa collected in two surveys in 2007 and 2008. 

PMID- 25057250
TI  - Report on the occurrence of synanthropic derived form of Chrysomyamegacephala
      (Diptera: Calliphoridae) from Royapuram fishing harbour, Chennai, Tamil Nadu,
      India.
AB  - The occurrence of dipteran fly, Chrysomyamegacephala (Fabricius, 1794) is
      reported for the first time from Royapuram fishing harbour (Chennai), Tamil Nadu,
      South East India. The fully grown third instar larvae of Chrysomyamegacephala
      were collected from decaying fishes near Royapuram fishing harbour. This site is
      found to be the regular breeding site for Chrysomyamegacephala. Larvae were
      reared under laboratory condition and freshly emerged adult flies from pupae were
      collected and identified by morphological features and molecular tools. Molecular
      identification through generation of DNA barcoding using mitochondrial COI gene
      of Chrysomyamegacephala is appended. 

PMID- 25057251
TI  - Checklist of british and irish hymenoptera - introduction.

PMID- 25057252
TI  - Symbiota - A virtual platform for creating voucher-based biodiversity information
      communities.
AB  - We review the Symbiota software platform for creating voucher-based biodiversity
      information portals and communities. Symbiota was originally conceived to promote
      small- to medium-sized, regionally and/or taxonomically themed collaborations of
      natural history collections. Over the past eight years the taxonomically diverse
      portals have grown into an important resource in North America and beyond for
      mobilizing, integrating, and using specimen- and observation-based occurrence
      records and derivative biodiversity information products. Designed to mirror the
      conceptual structure of traditional floras and faunas, Symbiota is exclusively
      web-based and employs a novel data model, information linking, and algorithms to
      provide highly dynamic customization. The themed portals enable meaningful access
      to biodiversity data for anyone from specialist to high school student. Symbiota
      emulates functionality of modern Content Management Systems, providing highly
      sophisticated yet intuitive user interfaces for data entry, batch processes, and
      editing. Each kind of content provision may be selectively accessed by
      authenticated information providers. Occupying a fairly specific niche in the
      biodiversity informatics arena, Symbiota provides extensive data exchange
      facilities and collaborates with other development projects to incorporate and
      not duplicate functionality as appropriate. 

PMID- 25057253
TI  - The high alpine bee fauna (Hymenoptera: Apoidea) of the Zillertal Alps, Austria.
AB  - Bees from the Zemmgrund area in the Zillertal Alps (Austria, Tyrol) were
      collected and determined to investigate the species composition of the area. A
      total of 61 specimens were collected over a two year period; they represent 24
      species from 8 genera. Building on these records, the first commented checklist
      for the area is presented, with notes on habitats and visited flowers. 

PMID- 25057254
TI  - Checklist of british and irish hymenoptera - evanioidea.

PMID- 25057256
TI  - A dataset for examining trends in publication of new Australian insects.
AB  - Australian Faunal Directory data were used to create a new, publicly available
      dataset, nai50, which lists 18318 species and subspecies names for Australian
      insects described in the period 1961-2010, together with associated publishing
      data. The number of taxonomic publications introducing the new names varied
      little around a long-term average of 70 per year, with ca 420 new names published
      per year during the 30-year period 1981-2010. Within this stable pattern there
      were steady increases in multi-authored and 'Smith in Jones and Smith' names, and
      a decline in publication of names in entomology journals and books. For taxonomic
      works published in Australia, a publications peak around 1990 reflected increases
      in museum, scientific society and government agency publishing, but a subsequent
      decline is largely explained by a steep drop in the number of papers on insect
      taxonomy published by Australia's national science agency, CSIRO. 

PMID- 25057255
TI  - Enriched biodiversity data as a resource and service.
AB  - BACKGROUND: Recent years have seen a surge in projects that produce large volumes
      of structured, machine-readable biodiversity data. To make these data amenable to
      processing by generic, open source "data enrichment" workflows, they are
      increasingly being represented in a variety of standards-compliant interchange
      formats. Here, we report on an initiative in which software developers and
      taxonomists came together to address the challenges and highlight the
      opportunities in the enrichment of such biodiversity data by engaging in
      intensive, collaborative software development: The Biodiversity Data Enrichment
      Hackathon. RESULTS: The hackathon brought together 37 participants (including
      developers and taxonomists, i.e. scientific professionals that gather, identify,
      name and classify species) from 10 countries: Belgium, Bulgaria, Canada, Finland,
      Germany, Italy, the Netherlands, New Zealand, the UK, and the US. The
      participants brought expertise in processing structured data, text mining,
      development of ontologies, digital identification keys, geographic information
      systems, niche modeling, natural language processing, provenance annotation,
      semantic integration, taxonomic name resolution, web service interfaces, workflow
      tools and visualisation. Most use cases and exemplar data were provided by
      taxonomists. One goal of the meeting was to facilitate re-use and enhancement of
      biodiversity knowledge by a broad range of stakeholders, such as taxonomists,
      systematists, ecologists, niche modelers, informaticians and ontologists. The
      suggested use cases resulted in nine breakout groups addressing three main
      themes: i) mobilising heritage biodiversity knowledge; ii) formalising and
      linking concepts; and iii) addressing interoperability between service platforms.
      Another goal was to further foster a community of experts in biodiversity
      informatics and to build human links between research projects and institutions,
      in response to recent calls to further such integration in this research domain.
      CONCLUSIONS: Beyond deriving prototype solutions for each use case, areas of
      inadequacy were discussed and are being pursued further. It was striking how many
      possible applications for biodiversity data there were and how quickly solutions
      could be put together when the normal constraints to collaboration were broken
      down for a week. Conversely, mobilising biodiversity knowledge from their silos
      in heritage literature and natural history collections will continue to require
      formalisation of the concepts (and the links between them) that define the
      research domain, as well as increased interoperability between the software
      platforms that operate on these concepts.

PMID- 25057257
TI  - The land crab Johngarthiaplanata (Stimpson, 1860) (Crustacea, Brachyura,
      Gecarcinidae) colonizes human-dominated ecosystems in the continental mainland
      coast of Mexico.
AB  - The land crab Johngarthiaplanata (Stimpson, 1860) has been reported from the Baja
      California Peninsula and several oceanic islands in the Eastern Pacific as well
      as inshore islands of the Mexican, Costa Rican and Colombian coast. However, the
      species has not been observed on the continental mainland, as it is likely that
      the high diversity of terrestrial predators/competitors make the establishment of
      mainland populations nearly impossible. In this contribution, several new records
      of this species that have been observed in urban areas along the continental
      Pacific coast of Mexico are reported. These records demonstrate that the presence
      of humans does not necessarily have a negative impact on land crab species.
      Indeed, the presence of humans may actually discourage the presence of native
      crab predators/competitors and hence increase the likelihood of a successful
      mainland settlement of land crab species that are otherwise island and peninsula
      restricted. The presence of Johngarthiaplanata is ecologically relevant for
      coastal forests because gecarcinid crabs significantly influence plant
      recruitment and Johngarthiaplanata is considerably larger than the mainland
      species Gecarcinusquadratus. 

PMID- 25057258
TI  - Exploring spirituality among youth in foster care: findings from the Casey Field
      Office Mental Health Study.
AB  - This study examined spiritual coping mechanisms, beliefs about spirituality and
      participation in spiritual activities and in other positive activities among
      adolescents in foster care. A multidimensional measure of spirituality was
      developed for face-to-face interviews with 188 youth (ages 14-17) from diverse
      racial/ethnic backgrounds in the United States. Findings revealed 95% of youth
      believe in God, over 70% believe God is 'creator' and God is 'love', and 79%
      considered prayer a spiritual practice. Most youth said love and forgiveness help
      them heal. Two-thirds (67%) reported responding to 'bad or tragic things
      happening' by spending time alone, and over half responded by praying (59%) or
      sharing the problem with someone else (56%). Youth's top three spiritual goals
      were to follow God's plan for them, become a better person, and know their
      purpose in life. Based on the value youth ascribed to spiritual coping
      mechanisms, recommendations for policy and practice focus on the integration of
      spirituality into practice and caregiving for youth in foster care.

PMID- 25057259
TI  - Health and development among Mexican, black and white preschool children: An
      integrative approach using latent class analysis.
AB  - BACKGROUND: Building on an emerging scientific consensus that the concept of
      child health should encompass chronic conditions, functional abilities, and
      developmental domains, we delineate the multidimensional health statuses of
      Mexican, non-Hispanic black, and non-Hispanic white preschool children in the
      United States. This integrative approach provides the foundation for an in-depth
      analysis of health disparities. OBJECTIVE: The research objectives are: (1) to
      demonstrate a new methodological approach to identifying the major child health
      statuses; (2) to document differences in the prevalence of those health statuses
      among children in the largest ethnoracial groups in the U.S.; and (3) to assess
      whether key sources of disadvantage account for ethnoracial disparities in
      children's health. METHODS: With data from a nationally representative sample, we
      use latent class analysis to estimate a set of latent health statuses that
      capture the nature of health at age four. The latent class membership of children
      is predicted using multinomial logistic regression. RESULTS: Mexican and non
      Hispanic black children are more likely than non-Hispanic white children to fall
      into health statuses distinguished by low cognitive achievement and multiple
      developmental problems. Mexican children are the most likely to be classified
      into these problematic health statuses. This pattern persists in multivariate
      models that incorporate potential explanatory factors, including health at birth,
      socio-demographic characteristics, home environment, well-child care and center
      based child care. CONCLUSIONS: Latent class analysis is a useful method for
      incorporating measures of physical conditions, functional problems, and
      development into a single analysis in order to identify key dimensions of
      childhood health and locate ethnoracial health disparities.

PMID- 25057260
TI  - Intensive care staff, the donation request and relatives' satisfaction with the
      decision: a focus group study.
AB  - BACKGROUND: Effectiveness of the donation request is generally measured by
      consent rates, rather than by relatives' satisfaction with their decision. Our
      aim was to elicit Dutch ICU staffs' views and experiences with the donation
      request, to investigate their awareness of (dis)satisfaction with donation
      decisions by relatives, specifically in the case of refusal, and to collect
      advice that may leave more relatives satisfied with their decision. METHODS: Five
      focus groups with a total of 32 participants (IC physicians, IC nurses and
      transplant coordinators) from five university hospitals in the Netherlands.
      Transcripts were examined using standard qualitative methods. RESULTS: Four
      themes (donation request perceived by ICU staff from the perspective of
      relatives; donation request perceived by ICU staff from their own perspective;
      aftercare; donation in society) divided into 14 categories were identified.
      According to ICU staff, relatives mentioned their own values more frequently than
      values of the potential donor as important for the decision. ICU staff observed
      this imbalance, but reacted empathically to the relatives' point of view. ICU
      staff rarely suggested reconsideration of refusal and did not ask relatives for
      arguments. ICU staff did not always feel comfortable with a request in the
      delicate context of brain death. Sometimes the interests of patient, relatives
      and those on the waiting list were irreconcilable. ICU staff were mostly unaware
      of relatives' regret following their decisions. Aftercare did not provide this
      type of information. Donation request by IC physicians was influenced by the way
      organ donation has been regulated in society (law, donor register, education,
      media). CONCLUSIONS: Our findings lead to the hypothesis that giving relatives
      more time and inviting them to reconsider their initial refusal will lead to a
      more stable decision and possibly more consent.

PMID- 25057261
TI  - Evaluation and clinical significance of the stomach age model for evaluating
      aging of the stomach-a multicenter study in China.
AB  - BACKGROUND: A higher prevalence of chronic atrophic gastritis (CAG) occurs in
      younger adults in Asia. We used Stomach Age to examine the different mechanisms
      of CAG between younger adults and elderly individuals, and established a simple
      model of cancer risk that can be applied to CAG surveillance. METHODS: Stomach
      Age was determined by FISH examination of telomere length in stomach biopsies.
      Deltapsim was also determined by flow cytometry. Sixty volunteers were used to
      confirm the linear relationship between telomere length and age while 120
      subjects were used to build a mathematical model by a multivariate analysis.
      Overall, 146 subjects were used to evaluate the validity of the model, and 1,007
      subjects were used to evaluate the relationship between prognosis and Deltaage
      (calculated from the mathematical model). ROC curves were used to evaluate the
      relationship between prognosis and Deltaage and to determine the cut-off point
      for Deltaage. RESULTS: We established that a tight linear relationship between
      the telomere length and the age. The telomere length was obvious different
      between patients with and without CAG even in the same age. Deltapsim decreased
      in individuals whose Stomach Age was greater than real age, especially in younger
      adults. A mathematical model of Stomach Age (real age + Deltaage) was
      successfully constructed which was easy to apply in clinical work. A higher
      Deltaage was correlated with a worse outcome. The criterion of Deltaage >3.11
      should be considered as the cut-off to select the subgroup of patients who
      require endoscopic surveillance. CONCLUSION: Variation in Stomach Age between
      individuals of the same biological age was confirmed. Attention should be paid to
      those with a greater Stomach Age, especially in younger adults. The Deltaage in
      the Simple Model can be used as a criterion to select CAG patients for gastric
      cancer surveillance.

PMID- 25057262
TI  - Clinical chemistry profiles in injection heroin users from Coastal Region, Kenya.
AB  - BACKGROUND: Although the co-burden of injection drug use and HIV is increasing in
      Africa, little is known about the laboratory markers of injection drug use and
      anti-retroviral treatment (ART) in Kenyan injection drug users. This study,
      therefore, aimed at determining the clinical chemistry profiles and identifying
      the key laboratory markers of HIV infection during ART in injection heroin users
      (IHUs). METHODS: Clinical chemistry measurements were performed on serum samples
      collected from HIV-1 infected ART-experienced (n = 22), naive (n = 16) and HIV-1
      negative (n = 23) IHUs, and healthy controls (n = 15) from Mombasa, coastal
      Kenya. RESULTS: HIV uninfected IHUs had lower alanine aminotransferase (ALT)
      levels (P = 0.023) as ART-exposed IHUs exhibited lower albumin (P = 0.014) and
      higher AST to platelet index (APRI) (P < 0.0001). All IHUs presented with lower
      aspartate aminotransferase to ALT values (P = 0.001) and higher C-reactive
      protein (CRP) levels (P = 0.002). ART-naive IHUs had higher globulin levels (P =
      0.013) while ART-experienced and naive IHUs had higher albumin to total protein
      (P < 0.0001) and albumin to globulin (P < 0.0001) values. In addition, CD4+ T
      cells correlated with ALT (rho = -0.522, P = 0.011) and CRP (rho, rho = 0.529, P
      = 0.011) in HIV negative and ART-experienced IHUs, respectively. HIV-1 viral load
      correlated with albumin to globulin index in ART-experienced (rho = -0.468, P =
      0.037) and naive (rho = -0.554, P = 0.040) IHUs; and with albumin to total
      protein index (rho = -0.554, P = 0.040) and globulin (rho = 0.570, P = 0.033) in
      ART-naive IHUs. CONCLUSION: Absolute ALT, albumin, globulin, and CRP measurements
      in combination with APRI, AST to ALT, albumin to total protein and albumin to
      globulin indices may be useful laboratory markers for screening IHUs for
      initiating and monitoring treatment.

PMID- 25057263
TI  - Comparative proteomic analysis of the membrane proteins of two Haemophilus
      parasuis strains to identify proteins that may help in habitat adaptation and
      pathogenesis.
AB  - BACKGROUND: Haemophilus parasuis is the causative agent of Glasser's disease
      characterized by polyserositis, arthritis, and meningitis in pig, leading to
      serious economic loss. Despite many years of study, virulence factors and the
      mechanisms of the entire infection process remain largely unclear. So two
      dimensional gel electrophoresis and mass spectrometry were used to search for
      distinctions at the membrane protein expression level between two H. parasuis
      isolates aimed at uncovering some proteins potentially involved in habitat
      adaption and pathogenesis. RESULTS: A comparative proteomic approach combining
      two-dimensional gel electrophoresis with mass spectrometry and tandem mass
      spectrometry was employed to explore the differences among membrane proteomes of
      a virulent Haemophilus parasuis strain isolated from the lung of a diseased pig
      and an avirulent strain isolated from the nasal swab of a healthy pig.
      Differentially expressed protein spots identified by mass spectrometry were
      annotated and analyzed by bioinformatic interpretation. The mRNA level was
      determined by quantitative real-time PCR. Proteins representing diverse
      functional activities were identified. Among them, the tonB-dependent siderophore
      receptor was a new discovery highlighted for its activity in iron uptake. In
      addition, periplasmic serine protease and putrescine/spermidine ABC transporter
      substrate-binding protein were given focus because of their virulence potential.
      This study revealed that the differentially expressed proteins were important in
      either the habitat adaption or pathogenesis of H. parasuis. CONCLUSIONS: The
      outcome demonstrated the presence of some proteins which raise the speculation
      for their importance in helping in habitat adaption or pathogenesis within the
      host.

PMID- 25057264
TI  - Parental Psychological Control and Adolescent Adjustment: The Role of Adolescent
      Emotion Regulation.
AB  - OBJECTIVE: This study investigated associations between parental psychological
      control and aggressive behavior and depressive symptoms among adolescents from
      predominantly disadvantaged backgrounds. The indirect effects of psychological
      control on adolescent adjustment through adolescent emotion regulation (anger and
      sadness regulation) were examined as well as the moderating effects of adolescent
      emotion regulation. DESIGN: 206 adolescents (ages 10-18) reported on parental
      psychological control and their own depressive symptoms, and parents and
      adolescents reported on adolescent emotion regulation and aggressive behavior.
      Indirect effect models were tested using structural equation modeling; moderating
      effects were tested using hierarchical multiple regression. RESULTS: The
      associations between parental psychological control and adolescent aggressive
      behavior and depressive symptoms were indirect through adolescents' anger
      regulation. Moderation analyses indicated that the association between parental
      psychological control and adolescent depressive symptoms was stronger among
      adolescents with poor sadness regulation and the association between
      psychological control and aggressive behavior was stronger among older
      adolescents with poor anger regulation. CONCLUSIONS: Psychological control is
      negatively associated with adolescent adjustment, particularly among adolescents
      who have difficulty regulating emotions. Emotion regulation is one mechanism
      through which psychological control is linked to adolescent adjustment,
      particularly anger dysregulation, and this pattern holds for both younger and
      older adolescents and for both boys and girls.

PMID- 25057265
TI  - Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in
      juvenile idiopathic arthritis: results of the Phase 4 registry.
AB  - BACKGROUND: This study aimed to assess long-term safety and developmental data on
      juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice
      with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs).
      METHODS: Children aged >=2 to <18 years with rheumatoid-factor-positive or 
      negative polyarthritis, persistent or extended oligoarthritis, or systemic
      arthritis were enrolled into this prospective, observational, multicenter
      standard-of-care registry. Eligible patients were newly or recently prescribed
      (<=6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end
      of the study, whether they remained on the original NSAID, switched, or
      discontinued therapy altogether. All adverse events (AEs) regardless of severity
      were captured in the database. RESULTS: A total of 274 patients (nsNSAID, n =
      219; celecoxib, n = 55) were observed for 410 patient-years of observation.
      Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At
      baseline, the celecoxib group was older, had a numerically longer median time
      since diagnosis, and a numerically higher proportion of patients with a history
      of gastrointestinal-related NSAID intolerance. AEs reported were those frequently
      observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%;
      celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs;
      the most frequent were infections, and none was attributed to NSAID use.
      CONCLUSIONS: The safety profile of celecoxib and nsNSAIDs appears similar
      overall. The results from this registry, ongoing pharmacovigilance, and the phase
      3 trial that led to the approval of celecoxib for children with JIA provide
      evidence that the benefit-risk for celecoxib treatment in JIA remains positive.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00688545.

PMID- 25057266
TI  - Effects of soluble milk protein or casein supplementation on muscle fatigue
      following resistance training program: a randomized, double-blind, and placebo
      controlled study.
AB  - BACKGROUND: The effects of protein supplementation on muscle thickness, strength
      and fatigue seem largely dependent on its composition. The current study compared
      the effects of soluble milk protein, micellar casein, and a placebo on strength
      and fatigue during and after a resistance training program. METHODS: Sixty-eight
      physically active men participated in this randomized controlled trial and
      underwent 10 weeks of lower-body resistance training. Participants were randomly
      assigned to the Placebo (PLA), Soluble Milk Protein (SMP, with fast digestion
      rate) or Micellar Casein (MC, with slow digestion rate) group. During the 10-week
      training period, participants were instructed to take 30 g of the placebo or
      protein twice a day, or three times on training days. Tests were performed on
      quadriceps muscles at inclusion (PRE), after 4 weeks (MID) and after 10 weeks
      (POST) of training. They included muscle endurance (maximum number of repetitions
      during leg extensions using 70% of the individual maximal load), fatigue
      (decrease in muscle power after the endurance test), strength, power and muscle
      thickness. RESULTS: Muscle fatigue was significantly lower (P < 0.05) in the SMP
      group at MID and POST (-326.8 +/- 114.1 W and -296.6 +/- 130.1 W, respectively)
      as compared with PLA (-439.2 +/- 153.9 W and -479.2 +/- 138.1 W, respectively)
      and MC (-415.1 +/- 165.1 W and -413.7 +/- 139.4 W, respectively). Increases in
      maximal muscle power, strength, endurance and thickness were not statistically
      different between groups. CONCLUSIONS: The present study demonstrated that
      protein composition has a large influence on muscular performance after prolonged
      resistance training. More specifically, as compared with placebo or micellar
      casein, soluble milk protein (fast digestible) appeared to significantly reduce
      muscle fatigue induced by intense resistance exercise.

PMID- 25057267
TI  - Toward better annotation in plant metabolomics: isolation and structure
      elucidation of 36 specialized metabolites from Oryza sativa (rice) by using MS/MS
      and NMR analyses.
AB  - Metabolomics plays an important role in phytochemical genomics and crop breeding;
      however, metabolite annotation is a significant bottleneck in metabolomic
      studies. In particular, in liquid chromatography-mass spectrometry (MS)-based
      metabolomics, which has become a routine technology for the profiling of plant
      specialized metabolites, a substantial number of metabolites detected as MS peaks
      are still not assigned properly to a single metabolite. Oryza sativa (rice) is
      one of the most important staple crops in the world. In the present study, we
      isolated and elucidated the structures of specialized metabolites from rice by
      using MS/MS and NMR. Thirty-six compounds, including five new flavonoids and
      eight rare flavonolignan isomers, were isolated from the rice leaves. The MS/MS
      spectral data of the isolated compounds, with a detailed interpretation of MS
      fragmentation data, will facilitate metabolite annotation of the related
      phytochemicals by enriching the public mass spectral data depositories, including
      the plant-specific MS/MS-based database, ReSpect.

PMID- 25057268
TI  - A novel stable isotope labelling assisted workflow for improved untargeted LC
      HRMS based metabolomics research.
AB  - Many untargeted LC-ESI-HRMS based metabolomics studies are still hampered by the
      large proportion of non-biological sample derived signals included in the
      generated raw data. Here, a novel, powerful stable isotope labelling (SIL)-based
      metabolomics workflow is presented, which facilitates global metabolome
      extraction, improved metabolite annotation and metabolome wide internal
      standardisation (IS). The general concept is exemplified with two different
      cultivation variants, (1) co-cultivation of the plant pathogenic fungi Fusarium
      graminearum on non-labelled and highly 13C enriched culture medium and (2)
      experimental cultivation under native conditions and use of globally U-13C
      labelled biological reference samples as exemplified with maize and wheat.
      Subsequent to LC-HRMS analysis of mixtures of labelled and non-labelled samples,
      two-dimensional data filtering of SIL specific isotopic patterns is performed to
      better extract truly biological derived signals together with the corresponding
      number of carbon atoms of each metabolite ion. Finally, feature pairs are
      convoluted to feature groups each representing a single metabolite. Moreover, the
      correction of unequal matrix effects in different sample types and the
      improvement of relative metabolite quantification with metabolome wide IS are
      demonstrated for the F. graminearum experiment. Data processing employing the
      presented workflow revealed about 300 SIL derived feature pairs corresponding to
      87-135 metabolites in F. graminearum samples and around 800 feature pairs
      corresponding to roughly 350 metabolites in wheat samples. SIL assisted IS, by
      the use of globally U-13C labelled biological samples, reduced the median CV
      value from 7.1 to 3.6 % for technical replicates and from 15.1 to 10.8 % for
      biological replicates in the respective F. graminearum samples.

PMID- 25057270
TI  - Treatment of Vertigo: A Randomized, Double-Blind Trial Comparing Efficacy and
      Safety of Ginkgo biloba Extract EGb 761 and Betahistine.
AB  - A multicenter clinical trial was performed to compare the efficacy and safety of
      Ginkgo biloba extract EGb 761 and betahistine at recommended doses in patients
      with vertigo. One hundred and sixty patients (mean age 58 years) were randomly
      assigned to double-blind treatment with EGb 761 (240 mg per day) or betahistine
      (32 mg per day) for 12 weeks. An 11-point numeric analogue scale, the Vertigo
      Symptom Scale-short form, the Clinical Global Impression Scales and the Sheehan
      Disability Scale were used as outcome measures. Both treatment groups were
      comparable at baseline and improved in all outcome measures during the course of
      treatment. There was no significant intergroup difference with regard to changes
      in any outcome measure. Numerically, improvements of patients receiving EGb 761
      were slightly more pronounced on all scales. Clinical global impression was rated
      "very much improved" or "much improved" in 79% of patients treated with EGb 761
      and in 70% receiving betahistine. With 27 adverse events in 19 patients, EGb 761
      showed better tolerability than betahistine with 39 adverse events in 31
      patients. In conclusion, the two drugs were similarly effective in the treatment
      of vertigo, but EGb 761 was better tolerated. This trial is registered with
      controlled-trials.com ISRCTN02262139. 

PMID- 25057269
TI  - Response mechanisms of bacterial degraders to environmental contaminants on the
      level of cell walls and cytoplasmic membrane.
AB  - Bacterial strains living in the environment must cope with the toxic compounds
      originating from humans production. Surface bacterial structures, cell wall and
      cytoplasmic membrane, surround each bacterial cell and create selective barriers
      between the cell interior and the outside world. They are a first site of contact
      between the cell and toxic compounds. Organic pollutants are able to penetrate
      into cytoplasmic membrane and affect membrane physiological functions. Bacteria
      had to evolve adaptation mechanisms to counteract the damage originated from
      toxic contaminants and to prevent their accumulation in cell. This review deals
      with various adaptation mechanisms of bacterial cell concerning primarily the
      changes in cytoplasmic membrane and cell wall. Cell adaptation maintains the
      membrane fluidity status and ratio between bilayer/nonbilayer phospholipids as
      well as the efflux of toxic compounds, protein repair mechanisms, and degradation
      of contaminants. Low energy consumption of cell adaptation is required to provide
      other physiological functions. Bacteria able to survive in toxic environment
      could help us to clean contaminated areas when they are used in bioremediation
      technologies. 

PMID- 25057271
TI  - Primary small cell neuroendocrine carcinoma of paranasal sinuses.
AB  - Small cell neuroendocrine carcinoma of the paranasal sinuses is an extremely rare
      and aggressive neoplasm. Despite aggressive management, the tumor carries a poor
      prognosis, with a high risk of local recurrence or distant metastases. The
      management strategy is based on that for pulmonary small cell cancer and includes
      platinum-based chemotherapy combined with radiotherapy. We are reporting a case
      of an 89-year-old female patient diagnosed with small cell carcinoma of right
      sided ethmoid and sphenoid sinuses. The tumor was found to have invaded the right
      orbit and anterior cranial fossa. Metastases to cervical lymph nodes and bone
      were also found. Due to the extended stage and poor prognosis of the patient, the
      management plan is palliative chemoradiotherapy. 

PMID- 25057272
TI  - Bilateral hegu acupoints have the same effect on the heart rate variability of
      the healthy subjects.
AB  - Background. The specificity of acupuncture points (acupoints) is one of the key
      concepts in traditional acupuncture theory, but the question of whether there is
      adequate scientific evidence to prove or disprove specificity has been vigorously
      debated in recent years. Acupoint laterality is an important aspect of acupoint
      specificity. Data is particularly scarce regarding the laterality of the same
      channel, namesake acupoint located on opposite sides of the body. Our previous
      study results suggest that Neiguan acupoint (PC6) has the laterality. The aim of
      this study was to investigate whether Hegu (LI4) also has laterality from the
      perspective of heart rate variability. Methods. A total of twenty-eight healthy
      female volunteers were recruited for this study and were randomly separated into
      the group I (n = 14) and the group II (n = 14) according to the register order.
      In the group I, left LI4 was stimulated in the first epoch and the right LI4 was
      stimulated in the second epoch. In the group II, right LI4 was stimulated in the
      first epoch and left LI4 was stimulated in the second epoch. Electrocardiogram
      was recorded and heart rate variability was analyzed. Results. The results show
      that there were no significant differences of heart rate variablity between the
      group I and the group II in the time domain and in the frequency domain.
      Conclusions. Bilateral Hegu acupoints have the same effect on the heart rate
      variability of the healthy subjects. 

PMID- 25057273
TI  - Fenugreek Prevents the Development of STZ-Induced Diabetic Nephropathy in a Rat
      Model of Diabetes.
AB  - The present study aims to examine the protective effect of fenugreek and the
      underlying mechanism against the development of diabetic nephropathy (DN) in
      streptozotocin- (STZ-) induced diabetic rats. A rat model of diabetes was
      successfully established by direct injection of STZ and then the rats were
      administered an interventional treatment of fenugreek. Parameters of renal
      function, including blood glucose, albuminuria, hemoglobin A1c (HbA1c), dimethyl
      formamide (DMF), blood urine nitrogen (BUN), serum creatinine (Scr), and kidney
      index (KI), were detected in the three groups (Con, DN, and DF). Oxidative stress
      was determined by the activity of antioxidase. Extracellular matrix (ECM)
      accumulation and other morphological alterations were evaluated by means of
      immunohistochemistry and electron microscope. Quantitive (q)PCR was employed to
      detect the mRNA expression of transforming growth factor-beta1 (TGF-beta1) and
      connective tissue growth factor (CTGF) and protein expression was determined with
      western blot analysis. DN rats in the present study demonstrated a significant
      renal dysfunction, ECM accumulation, pathological alteration, and oxidative
      stress, while the symptoms were evidently reduced by fenugreek treatment.
      Furthermore, the upregulation of TGF-beta1 and CTGF at a transcriptional and
      translational level in DN rats was distinctly inhibited by fenugreek.
      Consequently, fenugreek prevents DN development in a STZ-induced diabetic rat
      model. 

PMID- 25057274
TI  - Astragalus Polysaccharide Protects Astrocytes from Being Infected by HSV-1
      through TLR3/NF-kappaB Signaling Pathway.
AB  - Astragalus polysaccharide (APS) is the most immunoreactive substance in
      Astragalus. APS can regulate the body's immunity and is widely used in many
      immune related diseases. However, till now, there is little information about its
      contribution to the protection of astrocytes infected by virus. Toll-like
      receptor 3 (TLR3) is a key component of the innate immune system and has the
      ability to detect virus infection and trigger host defence responses. This study
      was undertaken to elucidate the protective effect of APS on herpes simplex virus
      (HSV-1) infected astrocytes and the underlying mechanisms. The results showed
      that APS protected the astrocytes from HSV-1 induced proliferation inhibition
      along with increasing expression of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) markedly. Moreover, APS significantly promoted the
      expression of Toll-like receptor 3 (TLR3) and the activation of nuclear factor
      kappaB (NF-kappaB) in astrocytes. In addition, while astrocytes were pretreated
      with TLR3 antibody before adding HSV-1 and APS, the expression of TLR3, TNF
      alpha, and IL-6 and the activation of NF-kappaB decreased sharply. These results
      indicate that APS can protect astrocytes by promoting immunological function
      provoked by HSV-1 through TLR3/NF-kappaB pathway. 

PMID- 25057275
TI  - Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and
      Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent
      Mechanisms.
AB  - Electrical vagus nerve (VN) stimulation during sepsis attenuates tumor necrosis
      factor (TNF) production through the cholinergic anti-inflammatory pathway, which
      depends on the integrity of the VN and catecholamine production. To characterize
      the effect of electroacupuncture at ST36 (EA-ST36) on serum TNF, IL-6, nitrite,
      and HMGB1 levels and survival rates, based on VN integrity and catecholamine
      production, a sepsis model was induced in rats using cecal ligation and puncture
      (CLP). The septic rats were subsequently treated with EA-ST36 (CLP+ST36), and
      serum samples were collected and analyzed for cytokines levels. The serum TNF, IL
      6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower
      compared with the group without treatment, the survival rates were significantly
      higher (P < 0.05), and the acute organ injury induced by CLP was mitigated by EA
      ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of
      TNF in the CLP+ST36 group did not show a significant difference compared with the
      group without electrostimulation, and, similarly, no significant difference in
      serum TNF levels was found under the pharmacological blockade of catecholamines.
      These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum
      TNF levels through VN- and atecholamine-dependent mechanisms. 

PMID- 25057276
TI  - Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo
      controlled trial.
AB  - Introduction. The purpose of this trial was to evaluate the effect of
      pterostilbene on metabolic parameters. Methods. A prospective, randomized, double
      blind, and placebo-controlled study that enrolled 80 patients with a total
      cholesterol >=200 mg/dL and/or LDL >= 100 mg/dL. Subjects were divided into four
      groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice
      daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4)
      matching placebo twice daily for 6-8 weeks. Endpoints included lipids, blood
      pressure, and weight. Linear mixed models were used to examine and compare
      changes in parameters over time. Models were adjusted for age, gender, and race.
      Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P = 0.001)
      which was not seen with GE combination (P = 0.47). Presence of a baseline
      cholesterol medication appeared to attenuate LDL effects. Both systolic (-7.8
      mmHg; P < 0.01) and diastolic blood pressure (-7.3 mmHg; P < 0.001) were reduced
      with high dose pterostilbene. Patients not on cholesterol medication (n = 51)
      exhibited minor weight loss with pterostilbene (-0.62 kg/m(2); P = 0.012).
      Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults.
      This trial is registered with Clinicaltrials.gov NCT01267227. 

PMID- 25057277
TI  - Cerebral microsporidiosis manifesting as progressive multifocal
      leukoencephalopathy in an HIV-infected individual - a case report.
AB  - Microsporidia have become increasingly recognized as opportunistic pathogens
      since the genesis of the AIDS epidemic. The incidence of microsporidiosis has
      decreased with the advent of combination antiretroviral therapy but it is
      frequently reported in non-HIV immunosuppressed patients and as a latent
      infection in immunocompetent individuals. Herein, we describe an HIV-infected
      male (46 years) with suspected progressive multifocal leukoencephalopathy that
      has not responded to optimal antiretroviral therapy, steroids, or cidofovir. Post
      mortem examination revealed cerebral microsporidiosis. No diagnostic clue
      however, was found when the patient was alive. This report underscores the need
      for physicians to consider microsporidiosis (potentially affecting the brain)
      when no other etiology is established both in HIV, non-HIV immunosuppressed
      patients and in immunocompetent individuals. 

PMID- 25057278
TI  - A novel approach for estimating the nationwide incidence of renal cancer.
AB  - BACKGROUND: The aim of this study was to provide a novel approach for estimating
      the incidence of renal cancer in Germany by using hospitalization data from the
      years 2005-2006 and to compare these estimates with incidence rates from cancer
      registries. We used nationwide hospitalization data from the years 2005-2006
      including 34.2 million hospitalizations. We used three definitions of potential
      incident renal cancer cases: 1) a main or secondary diagnosis of renal cancer and
      a partial or total nephrectomy; 2) a main diagnosis of renal cancer and a partial
      or total nephrectomy; and 3) a main diagnosis of renal cancer (without a
      secondary diagnosis of renal pelvis cancer) and a partial or total nephrectomy.
      In addition, we used cancer registry data for comparison of rates. RESULTS:
      Hospitalization data to which definition 2 applied provided incidence rate
      estimates nearly identical to those provided by the cancer registries (when the
      cases registered from death certificates only were excluded). Age-standardized
      (European standard population) incidence rates based on hospitalization data and
      cancer registry data were 15.6 per 100 000 and 15.7 per 100 000 among men and 8.0
      per 100 000 and 7.6 per 100 000 among women respectively. Cancer registry-based
      incidence rates were lower especially among those federal states with an
      estimated completeness of registration below 90% (Berlin and Saxony-Anhalt).
      CONCLUSIONS: Representative hospitalization data can be used to estimate
      incidence rates of renal cancer. We propose that incidence rates can be estimated
      by hospitalization data if 1) the primary treatment is performed during an in
      hospital stay and 2) nearly all patients undergo a defined surgical procedure
      that is not repeated for the treatment of the same cancer. Our results may be
      useful for countries with no or incomplete cancer registration or for countries
      that use hospitalization data to provide a representative incidence of renal
      cancer.

PMID- 25057279
TI  - Historical biogeography of the neotropical Diaptomidae (Crustacea: Copepoda).
AB  - INTRODUCTION: Diaptomid copepods are prevalent throughout continental waters of
      the Neotropics, yet little is known about their biogeography. In this study we
      investigate the main biogeographical patterns among the neotropical freshwater
      diaptomid copepods using Parsimony Analysis of Endemicity (PAE) based on species
      records within ecoregions. In addition, we assess potential environmental
      correlates and limits for species richness. RESULTS: PAE was efficient in
      identifying general areas of endemism. Moreover, only ecoregion area showed a
      significant correlation with diaptomid species richness, although climatic
      factors were shown to provide possible upper limits to the species richness in a
      given ecoregion. CONCLUSION: The main patterns of endemism in neotropical
      freshwater diaptomid copepods are highly congruent with other freshwater taxa,
      suggesting a strong historical signal in determining the distribution of the
      family in the Neotropics.

PMID- 25057280
TI  - Factors affecting the levels of protection transferred from mother to offspring
      following immune challenge.
AB  - INTRODUCTION: The transfer of antibodies from mother to offspring is key to
      protecting young animals from disease and can have a major impact on responses to
      infection and offspring fitness. Such maternal effects also allow young that may
      be exposed to disease in early life to focus resources on growth and development
      at this critical period of development. Maternally transferred antibodies are
      therefore an important source of phenotypic variation in host phenotype as well
      as influencing host susceptibility and tolerance to infection across generations.
      It has previously been assumed the transfer of antibodies is passive and
      invariant and reflects the level of circulating antibody in the mother at the
      time of transfer. However, whether females may vary in the relative amount of
      protection transferred to offspring has seldom been explored. RESULTS: Here we
      show that females differ widely in the relative amount of specific blood
      antibodies they transfer to the embryonic environment (range 9.2%-38.4% of their
      own circulating levels) in Chinese painted quail (Coturnix chinensis). Relative
      transfer levels were unrelated to the size of a female's own immune response.
      Furthermore, individual females were consistent in their transfer level, both
      across different stages of their immune response and when challenged with
      different vaccine types. The amount of antibody transferred was related to female
      condition, but baseline antibody responses of mothers were not. However, we found
      no evidence for any trade-offs between the relative amount of antibody
      transferred with other measures of reproductive investment. CONCLUSIONS: These
      results suggest that the relative amount of antibodies transferred to offspring
      can vary significantly and consistently between females. Levels of transfer may
      therefore be a separate trait open to manipulation or selection with potential
      consequences for offspring health and fitness in both wild and domesticated
      populations.

PMID- 25057281
TI  - Are antimicrobial defences in bird eggs related to climatic conditions associated
      with risk of trans-shell microbial infection?
AB  - INTRODUCTION: All bird eggs are exposed to microbes in the environment, which if
      transmitted to the developing embryo, could cause hatching failure. However, the
      risk of trans-shell infection varies with environmental conditions and is higher
      for eggs laid in wetter environments. This might relate to generally higher
      microbial abundances and diversity in more humid environments, including on the
      surface of eggshells, as well as the need for moisture to facilitate microbial
      penetration of the eggshell. To protect against microbial infection, the albumen
      of avian eggs contains antimicrobial proteins, including lysozyme and
      ovotransferrin. We tested whether lysozyme and ovotransferrin activities varied
      in eggs of larks (Alaudidae) living along an arid-mesic gradient of environmental
      aridity, which we used as a proxy for risk of trans-shell infection. RESULTS:
      Contrary to expectations, lysozyme activity was highest in eggs from hotter, more
      arid locations, where we predicted the risk of trans-shell infection would be
      lower. Ovotransferrin concentrations did not vary with climatic factors.
      Temperature was a much better predictor of antimicrobial protein activity than
      precipitation, a result inconsistent with studies stressing the importance of
      moisture for trans-shell infection. CONCLUSIONS: Our study raises interesting
      questions about the links between temperature and lysozyme activity in eggs, but
      we find no support for the hypothesis that antimicrobial protein deposition is
      higher in eggs laid in wetter environments.

PMID- 25057282
TI  - Work-related outcomes in randomised placebo-controlled pain trials: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Chronic painful conditions have an important influence on the ability
      to work. Work-related outcomes, however, are not commonly reported in
      publications on trials investigating the treatment of chronic painful conditions.
      We aim to provide an overview of the reporting of work-related outcomes in such
      trials and investigate the relationship between work-related outcomes and pain
      outcomes. METHODS: We conducted a systematic literature search in PubMed with the
      aim of identifying randomised placebo-controlled clinical trials investigating
      treatments for chronic painful conditions or rheumatic diseases that also
      reported on work-related outcomes. Methodological study quality was assessed with
      the Oxford Quality Scale (OQS). Meta-analyses were conducted for the outcomes of
      interference with work and number of patients with at least 30% reduction in pain
      intensity (30% pain responders). The correlation between work-related and pain
      outcomes was investigated with regression analyses. RESULTS: We included 31
      publications reporting on 27 datasets from randomised placebo-controlled trials
      (with a total of 11,434 study participants) conducted in chronic painful or
      rheumatic diseases and reporting on work-related outcomes. These 31 publications
      make up only about 0.2% of all publications on randomised placebo-controlled
      trials in such conditions. The methodological quality of the included studies was
      high; only nine studies scored less than four (out of a maximum five) points on
      the OQS. Sixteen different work-related outcomes were reported on in the studies.
      Of 25 studies testing for the statistical significance of changes in work-related
      outcomes over the course of the trials, 14 (56%) reported a significant
      improvement; the others reported non-significant changes. Eight studies reported
      data on both interference with work and 30% pain responders: meta-analyses
      demonstrated similar, statistically significant improvements in both these
      outcomes with active therapy compared to placebo and regression analysis showed
      that these outcomes were correlated. CONCLUSIONS: Despite the importance of pain
      as a reason for decreased ability to work, work-related outcomes are reported in
      substantially less than 1% of publications on placebo-controlled trials in
      chronic painful and rheumatic diseases. Work-related outcomes and pain responder
      outcomes are closely related.

PMID- 25057283
TI  - Breastfeeding practice and associated factors among female nurses and midwives at
      North Gondar Zone, Northwest Ethiopia: a cross-sectional institution based study.
AB  - BACKGROUND: Health care workers have a duty to promote and support breastfeeding
      among their clients. Although their ability to do this may be influenced by their
      knowledge and personal experience; little is known about breastfeeding practices
      and the perceived barriers. The objective of this study was to assess the
      breastfeeding practices and the associated factors among female nurses and
      midwives in North Gondar Zone; Northwest Ethiopia. METHODS: An institution based
      cross-sectional study design was conducted in 2013 among 178 nurses and midwives.
      In this study exclusive breastfeeding refers to breastfeeding exclusively for the
      first six months of a child's life. Bivariate and multivariate logistic
      regressions were performed to identify the presence and strength of association.
      Odds ratios with 95% confidence interval were computed to determine the level of
      significance. RESULTS: Exclusive breastfeeding rate among respondents was found
      to be 35.9%. Nearly half (49.4%) of the respondents exclusively breastfed for
      only 3 months or less. The mean duration exclusive breastfeeding was 4.1 +/- 1.7
      months. Older women (AOR = 2.8; 95% CI 2.16, 3.24), rural residence (AOR = 3.01;
      95% CI 2.65, 3.84), being midwife (AOR = 2.01; 95% CI 1.83, 2.56), a women who
      gave birth through vaginal delivery (AOR = 2.0; 95% CI 1.68, 2.87), multiparous
      women (AOR = 2.20; 95% CI 1.74, 2.67) and resumption of work after 3 months (AOR
      = 1.61; 95% CI 1.24, 2.35) were independently associated with exclusive
      breastfeeding. CONCLUSION: Though respondents had adequate knowledge on
      breastfeeding, the practice of exclusive breastfeeding was low. Maternal age,
      place of residence, profession, mode of delivery, parity and the time before
      resuming work were factors associated with exclusive breastfeeding. Appropriate
      education concerning breastfeeding, directed at nurses and midwives is required
      to enhance exclusive breastfeeding and duration of breastfeeding.

PMID- 25057284
TI  - A mixture modeling framework for differential analysis of high-throughput data.
AB  - The inventions of microarray and next generation sequencing technologies have
      revolutionized research in genomics; platforms have led to massive amount of data
      in gene expression, methylation, and protein-DNA interactions. A common theme
      among a number of biological problems using high-throughput technologies is
      differential analysis. Despite the common theme, different data types have their
      own unique features, creating a "moving target" scenario. As such, methods
      specifically designed for one data type may not lead to satisfactory results when
      applied to another data type. To meet this challenge so that not only currently
      existing data types but also data from future problems, platforms, or experiments
      can be analyzed, we propose a mixture modeling framework that is flexible enough
      to automatically adapt to any moving target. More specifically, the approach
      considers several classes of mixture models and essentially provides a model
      based procedure whose model is adaptive to the particular data being analyzed. We
      demonstrate the utility of the methodology by applying it to three types of real
      data: gene expression, methylation, and ChIP-seq. We also carried out simulations
      to gauge the performance and showed that the approach can be more efficient than
      any individual model without inflating type I error. 

PMID- 25057285
TI  - Endoscopic reduction of a volvulus of the sigmoid colon in pregnancy: case report
      and a comprehensive review of the literature.
AB  - Sigmoid volvulus is a rare, but serious, complication that can occur during
      pregnancy. We present a case of a 33-year-old pregnant female in the third
      trimester with a sigmoid volvulus. Detorsion of the volvulus was performed during
      colonoscopy. The patient underwent an elective sigmoidectomy at a later date.
      Prompt diagnosis of the volvulus sigmoid is critical to minimize fetal and
      maternal morbidity and mortality. Sigmoidoscopic detorsion or surgical resection
      are the treatment options, depending on bowel viability. A review of the
      literature was done. 

PMID- 25057286
TI  - Psychosocial perception of adults with onychomycosis: a blinded, controlled
      comparison of 1,017 adult Hong Kong residents with or without onychomycosis.
AB  - BACKGROUND: A survey was conducted amongst 1,017 Hong Kong residents ages 18 and
      over to determine their knowledge of fungal nail infections (onychomycosis) and
      the psychosocial impact of the disease on the relationships, social lives and
      careers of sufferers. METHODS: The Fungal Nail Perception Survey was conducted by
      email and online between May 29th and June 10th, 2013. Participants were shown
      three photographs of people with and without onychomycosis of the toenails.
      Respondents were asked ten questions (repeated for each picture) to ascertain
      their perceptions of the people in the pictures. Questions were related to
      perceptions around the ability of sufferers and non-sufferers to form
      relationships with others, social activities of sufferers and non-sufferers,
      perceptions of the effect of the disease on the potential for career success, and
      awareness of fungal nail disease and health. The sub-population who themselves
      suffered from onychomycosis were asked about self-perception as well as their
      perception of others with onychomycosis. RESULTS: Compared with non-sufferers,
      survey respondents perceived those with onychomycosis as less likely to be able
      to form good relationships. They also indicated that they would be more likely to
      exclude sufferers than non-sufferers from social activities and that they would
      be more likely to feel uncomfortable when sitting or standing beside an infected
      person than beside an uninfected person. Respondents perceived people with
      onychomycosis to be less able to perform well in their chosen career than with
      someone without onychomycosis. Interestingly, those respondents who themselves
      were infected felt socially excluded, upset and embarrassed by their infection.
      CONCLUSIONS: Onychomycosis may lead to stigmatization and social exclusion.
      Misconceptions of onychomycosis are high and education about the disease needs to
      be improved. Early recognition and treatment of the disease is essential to avoid
      complications and improve treatment outcomes, which would lead to reduced
      psychosocial impact on those with fungal nail infections.

PMID- 25057287
TI  - Characterization of Argentine honeys on the basis of their mineral content and
      some typical quality parameters.
AB  - BACKGROUND: The levels of 19 elements (As, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn,
      Na, Ni, Pb, Se, Tl, U, V, Zn) from sixteen different Argentine production sites
      of unifloral [eucalyptus (Eucaliptus rostrata), chilca (Baccharis salicifolia),
      Algarrobo (Prosopis sp.), mistol (Ziziphus mistol) and citric] and multifloral
      honeys were measured with the aim to test the quality of the selected samples.
      Typical quality parameters of honeys were also determined (pH, sugar content,
      moisture). Mineral elements were determined by using inductively coupled plasma
      mass spectrometer (ICP-MS DRC). We also evaluated the suitability of honey as a
      possible biomonitor of environmental pollution. Thus, the sites were classified
      through cluster analysis (CA) and then pattern recognition methods such as
      Principal Component Analysis (PCA) and discriminant analysis (DA) were applied.
      RESULTS: MEAN VALUES FOR QUALITY PARAMETERS WERE: pH, 4.12 and 3.81; sugar 82.1
      and 82.0  degrees brix; moisture, 16.90 and 17.00% for unifloral and multifloral
      honeys respectively. The water content showed good maturity. Likewise, the other
      parameters confirmed the good quality of the honeys analysed. Potassium was
      quantitatively the most abundant metal, accounting for 92,5% of the total metal
      contents with an average concentration of 832.0 and 816.2 MUg g(-1) for unifloral
      and multifloral honeys respectively. Sodium was the second most abundant major
      metal in honeys with a mean value of 32.16 and 33.19 MUg g(-1) for unifloral and
      multifloral honeys respectively. Mg, Ca, Fe, Mn, Zn and Cu were present at low
      intermediate concentrations. For the other 11 trace elements determined in this
      study (As, Be, Cd, Co, Cr, Ni, Pb, Se, Tl, U and V), the mean concentrations were
      very low or below of the LODs. The sites were classified through CA by using
      elements' and physicochemical parameters data, then DA on the PCA factors was
      applied. Dendrograms identified three main groups. PCA explained 52.03% of the
      total variability with the first two factors. CONCLUSIONS: In general, there are
      no evidences of pollution for the analysed honeys. The analytical results
      obtained for the Argentine honeys indicate the products' high quality. In fact,
      most of the toxic elements were below LODs. The chemometric analysis combining
      CA, DA and PCA showed their aptness as useful tools for honey's classification.
      Eventually, this study confirms that the use of honey as biomonitor of
      environmental contamination is not reliable for sites with low levels of
      contamination.

PMID- 25057288
TI  - Nanotechnology in drug delivery: the need for more cell culture based studies in
      screening.
AB  - Advances in biomedical science are leading to upsurge synthesis of nanodelivery
      systems for drug delivery. The systems were characterized by controlled, targeted
      and sustained drug delivery ability. Humans are the target of these systems,
      hence, animals whose systems resembles humans were used to predict outcome. Thus,
      increasing costs in money and time, plus ethical concerns over animal usage.
      However, with consideration and planning in experimental conditions, in vitro
      pharmacological studies of the nanodelivery can mimic the in vivo system. This
      can function as a simple method to investigate the effect of such materials
      without endangering animals especially at screening phase. 

PMID- 25057289
TI  - Disturbances in attachment: inhibited and disinhibited symptoms in foster
      children.
AB  - BACKGROUND: Previous DSM-versions recognized an inhibited and a disinhibited
      subtype of the Reactive Attachment Disorder (RAD). The current DSM-5
      distinguishes two different disorders, instead of two subtypes of RAD. This study
      examined whether a split-up of the subtypes is valid. METHOD: In 126 foster
      children, attachment disorder symptoms were assessed with the Disturbances of
      Attachment Interview. Forms of pathogenic care were identified based on dossier
      analyses. Associations between symptoms of attachment disorder with internalizing
      and externalizing problems (Child Behavior Checklist and Teacher Report Form)
      were examined. RESULTS: Omnibus tests showed no significant association between
      type of symptoms and type of pathogenic care. Exploratory analyses did reveal an
      univariate association between disinhibited symptoms and history of physical
      abuse. Disinhibited symptoms were associated with more internalizing and
      externalizing problems (d's < 0.50). CONCLUSION: The distinction of inhibited and
      disinhibited subtypes of RAD seems valid regarding their emotional and behavioral
      correlations. Whereas inhibited symptoms lack a correlation, disinhibited
      symptoms seem to have an externalizing and internalizing correlation. TRIAL
      REGISTRATION: NTR1747.

PMID- 25057290
TI  - Engineered protein A ligands, derived from a histidine-scanning library,
      facilitate the affinity purification of IgG under mild acidic conditions.
AB  - BACKGROUND: In antibody purification processes, the acidic buffer commonly used
      to elute the bound antibodies during conventional affinity chromatograph, can
      damage the antibody. Herein we describe the development of several types of
      affinity ligands which enable the purification of antibodies under much milder
      conditions. RESULTS: Staphylococcal protein A variants were engineered by using
      both structure-based design and combinatorial screening methods. The frequency of
      amino acid residue substitutions was statistically analyzed using the sequences
      isolated from a histidine-scanning library screening. The positions where the
      frequency of occurrence of a histidine residue was more than 70% were thought to
      be effective histidine-mutation sites. Consequently, we identified PAB variants
      with a D36H mutation whose binding of IgG was highly sensitive to pH change.
      CONCLUSION: The affinity column elution chromatograms demonstrated that
      antibodies could be eluted at a higher pH (?pH**?2.0) than ever reported (?pH =
      1.4) when the Staphylococcal protein A variants developed in this study were used
      as affinity ligands. The interactions between Staphylococcal protein A and IgG
      Fab were shown to be important for the behavior of IgG bound on a SpA affinity
      column, and alterations in the affinity of the ligands for IgG-Fab clearly
      affected the conditions for eluting the bound IgG. Thus, a histidine-scanning
      library combined with a structure-based design was shown to be effective in
      engineering novel pH-sensitive proteins.

PMID- 25057291
TI  - An instrument design for non-contact detection of biomolecules and minerals on
      Mars using fluorescence.
AB  - We discuss fluorescence as a method to detect polycyclic aromatic hydrocarbons
      and other organic molecules, as well as minerals on the surface of Mars. We
      present an instrument design that is adapted from the ChemCam instrument which is
      currently on the Mars Science Lander Rover Curiosity and thus most of the primary
      components are currently flight qualified for Mars surface operations,
      significantly reducing development costs. The major change compared to ChemCam is
      the frequency multipliers of the 1064 nm laser to wavelengths suitable for
      fluorescence excitation (266 nm, 355 nm, and 532 nm). We present fluorescence
      spectrum for a variety of organics and minerals relevant to the surface of Mars.
      Preliminary results show minerals already known on Mars, such as perchlorate,
      fluoresce strongest when excited by 355 nm. Also we demonstrate that polycyclic
      aromatic hydrocarbons, such as those present in Martian meteorites, are highly
      fluorescent at wavelengths in the ultraviolet (266 nm, 355 nm), but not as much
      in the visible (532 nm). We conclude that fluorescence can be an important method
      for Mars applications and standoff detection of organics and minerals. The
      instrument approach described in this paper builds on existing hardware and
      offers high scientific return for minimal cost for future missions. 

PMID- 25057292
TI  - Meiotic prophase I defects in an oligospermic man with Wolf-Hirschhorn syndrome
      with ring chromosome 4.
AB  - BACKGROUND: Ring chromosomes are often associated with spermatogenetic failure.
      However, the mechanism is poorly understood. We here reported a single man with
      severe oligospermia and a ring chromosome 4 with a microdeletion at 4p16.3.
      RESULTS: Synapsis (as SCP3), recombination (as MLH1) and transcriptional
      inactivation (as BRCA1) in a testicular biopsy were examined by fluorescence
      immunostaining. In the oligospermia patient, 35.4% of spermatocytes were in
      zygotene phase compared with 5.2% in controls. The patient had a significantly
      reduced recombination frequency with mean of 45.9 MLH1 foci/cell compared with
      47.8 in controls. In the patient, chromosome 4 in all pachytene cells displayed
      loop formation with varying degrees of unpaired regions. BRCA1 localized along
      asynapsed regions regardless of XY body association. CONCLUSIONS: Ring chromosome
      4 might affect the progression of meiosis I prophase, synapse formation, and
      transcriptional activation of asynapsed areas, and impair male fertility.

PMID- 25057293
TI  - A classification and characterization of two-locus, pure, strict, epistatic
      models for simulation and detection.
AB  - BACKGROUND: The statistical genetics phenomenon of epistasis is widely
      acknowledged to confound disease etiology. In order to evaluate strategies for
      detecting these complex multi-locus disease associations, simulation studies are
      required. The development of the GAMETES software for the generation of complex
      genetic models, has provided the means to randomly generate an architecturally
      diverse population of epistatic models that are both pure and strict, i.e. all n
      loci, but no fewer, are predictive of phenotype. Previous theoretical work
      characterizing complex genetic models has yet to examine pure, strict, epistasis
      which should be the most challenging to detect. This study addresses three goals:
      (1) Classify and characterize pure, strict, two-locus epistatic models, (2)
      Investigate the effect of model 'architecture' on detection difficulty, and (3)
      Explore how adjusting GAMETES constraints influences diversity in the generated
      models. RESULTS: In this study we utilized a geometric approach to classify pure,
      strict, two-locus epistatic models by "shape". In total, 33 unique shape symmetry
      classes were identified. Using a detection difficulty metric, we found that model
      shape was consistently a significant predictor of model detection difficulty.
      Additionally, after categorizing shape classes by the number of edges in their
      shape projections, we found that this edge number was also significantly
      predictive of detection difficulty. Analysis of constraints within GAMETES
      indicated that increasing model population size can expand model class coverage
      but does little to change the range of observed difficulty metric scores. A
      variable population prevalence significantly increased the range of observed
      difficulty metric scores and, for certain constraints, also improved model class
      coverage. CONCLUSIONS: These analyses further our theoretical understanding of
      epistatic relationships and uncover guidelines for the effective generation of
      complex models using GAMETES. Specifically, (1) we have characterized 33 shape
      classes by edge number, detection difficulty, and observed frequency (2) our
      results support the claim that model architecture directly influences detection
      difficulty, and (3) we found that GAMETES will generate a maximally diverse set
      of models with a variable population prevalence and a larger model population
      size. However, a model population size as small as 1,000 is likely to be
      sufficient.

PMID- 25057294
TI  - Innovation is often unnerving: the door into summer.

PMID- 25057295
TI  - Hepatitis B virus treatment beyond the guidelines: special populations and
      consideration of treatment withdrawal.
AB  - The goal of chronic hepatitis B (CHB) treatment is to improve survival by
      preventing disease progression to decompensated cirrhosis and hepatocellular
      carcinoma which is the cause of over 1 million deaths annually. The risk of
      disease progression is reduced when a sustained reduction of hepatitis B virus
      (HBV) DNA to undetectable levels and suppression of HBV replication are obtained
      which can result in regression of liver fibrosis and may even reverse cirrhosis.
      However, even if HBsAg loss occurs, HBV is not completely eradicated by
      treatment, and long-term therapy is required in patients who are HBeAg(-) and
      HBeAg(+) who do not maintain off-treatment virological suppression and in those
      with advanced liver disease. The recently updated European Association of the
      Study of the Liver (EASL) clinical practical guidelines for HBV have clarified,
      first, how to treat HBV (interferon or the most potent oral drugs with optimal
      resistance profiles, i.e. entecavir and tenofovir disoproxil fumarate, should be
      used as first-line monotherapies); second, who should be treated (CHB in patients
      with significant liver disease but also patients who are HBsAg(+) and are
      receiving immunosuppressive treatment, patients coinfected with HBV and human
      immunodeficiency virus, mothers who are HBsAg(+) with high viral load in late
      pregnancy associated with sero vaccination to reduce the risk of vertical
      transmission of HBV; and third, when to stop antiviral therapies. The aim of this
      review was to clarify how to treat HBV and who should be treated, as well as when
      to stop treatment. Although the answer to these questions is clear for pegylated
      interferon, it is more debatable for nucleos(t)ide analogues (anti-HBe
      seroconversion, HBsAg loss or anti-HBs seroconversion with undetectable HBV DNA
      are clear indications to discontinue treatment but sustained undetectable HBV DNA
      in patients who are anti-HBe(+) without significant fibrosis might be another
      indication). 

PMID- 25057296
TI  - Colonic smooth muscle cells and colonic motility patterns as a target for
      irritable bowel syndrome therapy: mechanisms of action of otilonium bromide.
AB  - Otilonium bromide (OB) is a spasmolytic compound of the family of quaternary
      ammonium derivatives and has been successfully used in the treatment of patients
      with irritable bowel syndrome (IBS) due to its specific pharmacodynamic effects
      on motility patterns in the human colon and the contractility of colonic smooth
      muscle cells. This article examines how. OB inhibits the main patterns of human
      sigmoid motility in vitro, which are spontaneous rhythmic phasic contractions,
      smooth muscle tone, contractions induced by stimulation of excitatory motor
      neurons and contractions induced by direct effect of excitatory
      neurotransmitters. It does this mainly by blocking calcium influx through L-type
      calcium channels and interfering with mobilization of cellular calcium required
      for smooth muscle contraction, thereby limiting excessive intestinal
      contractility and abdominal cramping. OB also inhibits T-type calcium channels
      and muscarinic responses. Finally, OB inhibits tachykinin receptors on smooth
      muscle and primary afferent neurons which may have the joint effect of reducing
      motility and abdominal pain. All these mechanisms mediate the therapeutic effects
      of OB in patients with IBS and might be useful in patients with other spastic
      colonic motility disorders such as diverticular disease. 

PMID- 25057297
TI  - Elobixibat and its potential role in chronic idiopathic constipation.
AB  - Chronic idiopathic constipation is highly prevalent among adults. Bile acids
      (BAs) and the enterohepatic BA circulation modulate colonic secretion and
      motility that affect transit. BAs in the colon have a dual action as osmotic and
      stimulant agents. Newer agents, such as elobixibat (A3309), an inhibitor of the
      ileal BA transporter, have the potential to improve significantly the management
      of chronic constipation, with minimal adverse effects. Elobixibat modulates the
      enterohepatic BA circulation, enhancing the delivery of BAs to the colon where
      they induce secretory and motor effects. Secondary effects of the inhibition of
      BA absorption are reduced activation of the farnesoid X receptor, decreased
      secretion of fibroblast growth factor-19 into the portal circulation, and
      increased BA synthesis. This review focuses on the role of BAs, the enterohepatic
      BA circulation, and an ileal BA transporter inhibitor (elobixibat) in chronic
      constipation. 

PMID- 25057300
TI  - Detection, identification and quantification of Campylobacter jejuni, coli and
      lari in food matrices all at once using multiplex qPCR.
AB  - BACKGROUND: Thermotolerant Campylobacter jejuni, coli and lari are recognized as
      leading food-borne pathogens causing an acute bacterial enteritis worldwide. Due
      to narrow spectrum of their biochemical activity, it is very complicated to
      distinguish between individual species. For reliable risk assessment, proper
      incidence evaluation or swift sample analysis regarding individual species, a
      demand for simple and rapid method for their distinguishing is reasonable. In
      this study, we evaluated a reliable and simple approach for their simultaneous
      detection, species identification and quantification using multiplex qPCR.
      RESULTS: Species specific primers and hydrolysis probes are directed to
      hippuricase gene of C. jejuni, serine hydroxymethyltransferase gene of C. coli
      and peptidase T gene of C. lari. Efficiencies of reactions were 90.85% for C.
      jejuni, 96.97% for C. coli and 92.89% for C. lari. At 95.00% confidence level and
      when cut off is set to 38 cycles, limits of detection are in all cases under 10
      genome copies per reaction which is very appreciated since it is known that
      infectious doses are very low. CONCLUSIONS: Proposed assay was positively
      validated on different food matrices (chicken wing rinses, chicken juice and
      homogenized fried chicken strips). No inhibition of PCR reaction occurred. Assay
      was evaluated in accordance with MIQE handbook.

PMID- 25057298
TI  - Three-dimensional super-resolution microscopy of the inactive X chromosome
      territory reveals a collapse of its active nuclear compartment harboring distinct
      Xist RNA foci.
AB  - BACKGROUND: A Xist RNA decorated Barr body is the structural hallmark of the
      compacted inactive X territory in female mammals. Using super-resolution three
      dimensional structured illumination microscopy (3D-SIM) and quantitative image
      analysis, we compared its ultrastructure with active chromosome territories (CTs)
      in human and mouse somatic cells, and explored the spatio-temporal process of
      Barr body formation at onset of inactivation in early differentiating mouse
      embryonic stem cells (ESCs). RESULTS: We demonstrate that all CTs are composed of
      structurally linked chromatin domain clusters (CDCs). In active CTs the periphery
      of CDCs harbors low-density chromatin enriched with transcriptionally competent
      markers, called the perichromatin region (PR). The PR borders on a contiguous
      channel system, the interchromatin compartment (IC), which starts at nuclear
      pores and pervades CTs. We propose that the PR and macromolecular complexes in IC
      channels together form the transcriptionally permissive active nuclear
      compartment (ANC). The Barr body differs from active CTs by a partially collapsed
      ANC with CDCs coming significantly closer together, although a rudimentary IC
      channel system connected to nuclear pores is maintained. Distinct Xist RNA foci,
      closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A)
      localize throughout Xi along the rudimentary ANC. In early differentiating ESCs
      initial Xist RNA spreading precedes Barr body formation, which occurs concurrent
      with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a
      transgenic autosomal Xist RNA in a male ESC triggers the formation of an
      'autosomal Barr body' with less compacted chromatin and incomplete RNAP II
      exclusion. CONCLUSIONS: 3D-SIM provides experimental evidence for profound
      differences between the functional architecture of transcriptionally active CTs
      and the Barr body. Basic structural features of CT organization such as CDCs and
      IC channels are however still recognized, arguing against a uniform compaction of
      the Barr body at the nucleosome level. The localization of distinct Xist RNA foci
      at boundaries of the rudimentary ANC may be considered as snap-shots of a dynamic
      interaction with silenced genes. Enrichment of SAF-A within Xi territories and
      its close spatial association with Xist RNA suggests their cooperative function
      for structural organization of Xi.

PMID- 25057301
TI  - Transfusions and patient burden in chemotherapy-induced anaemia in France.
AB  - OBJECTIVES: To estimate the patient burden in terms of the time spent on
      outpatient red blood cell (RBC) transfusions indicated for chemotherapy induced
      anaemia (CIA) in patients with cancer in France. METHODS: A retrospective chart
      review of patients with cancer receiving an outpatient RBC transfusion was
      conducted at seven treatment centres in France. Total treatment time for one
      transfusion visit per patient was measured as the elapsed time between pre- and
      post-transfusion vital sign assessment, including time from transfusion start to
      stop. Elapsed time from haemoglobin (Hb) level testing to transfusion start and
      from blood draw for compatibility testing to transfusion start were recorded. In
      addition, estimated travel time and distance to the transfusion centre, and
      clinical and demographic information were collected. RESULTS: A total of 103
      patients [63.1% men; mean age 66.2 years, standard deviation (SD) 11.9] were
      enrolled in the study (1 August 2010-31 October 2010). The four most frequent
      diagnoses were lung cancer (31.1%), urological cancer (15.5%), gynecological
      cancer (14.6%) and gastrointestinal/colorectal cancer (14.6%). Mean elapsed time
      between prevital and postvital sign assessment was 4.0 h [95% confidence interval
      (CI) 1.9-6.1], including a mean of 3.4 h (95% CI 2.5-4.2) for the transfusion
      itself. Hb level testing (mean pre-transfusion Hb level 8.0 g/dl, SD 0.8) and
      blood draw for compatibility testing were completed in a mean of 28.8 h (95% CI
      1.3-56.2) and 9.4 h (95% CI 0-21.4) prior to transfusion respectively. Patients'
      one-way mean travel time to the transfusion centre was 32.9 min (95% CI 28.5
      37.4) and mean distance travelled was 25.4 km (95% CI 11.6-39.3). CONCLUSION: In
      France, CIA treatment with RBC transfusion is a time-consuming activity for
      patients that includes multiple trips to a medical facility, blood testing and
      the transfusion procedure itself. This burden is important to consider in the
      context of optimizing proactive monitoring and planning for supportive oncology
      care.

PMID- 25057302
TI  - The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers.
AB  - The phosphoinositide 3 kinase (PI3K)/Akt/mammalian (or mechanistic) target of
      rapamycin (mTOR) pathway is a complicated intracellular pathway, which leads to
      cell growth and tumor proliferation and plays a significant role in endocrine
      resistance in breast cancer. Multiple compounds targeting this pathway are being
      evaluated in clinical trials. These agents are generally well tolerated and can
      be used in combination with targeted therapies, endocrine therapy or cytotoxic
      agents. The identification of subtypes of tumors more likely to respond to these
      therapeutics cannot be overemphasized, since breast cancer is a very
      heterogeneous malignancy. Activation of pathways such as KRAS and MEK can act as
      escape mechanisms that lead to resistance, thus a combination of agents targeting
      multiple steps of the intracellular machinery is promising. There is evidence
      that tumors with PIK3CA mutations are more sensitive to inhibitors of the PI3K
      pathway but this has yet to be validated. Large clinical trials with correlative
      studies are necessary to identify reliable biomarkers of efficacy. 

PMID- 25057303
TI  - Castration-resistant prostate cancer: latest evidence and therapeutic
      implications.
AB  - Medical oncologists who treat men with castration-resistant prostate cancer
      (CRPC) have seen an abundance of new agents approved by the United States Food
      and Drug Administration in the last decade for a disease that was previously
      difficult to treat after becoming resistant to androgen-deprivation therapy.
      Advances in understanding of the mechanisms of castration-resistance and prostate
      cancer progression have highlighted several pathways and targets that appear
      promising to better treat CRPC. As the majority of CRPC appears to continue to
      rely on the androgen receptor for growth and progression, several of these agents
      directly or indirectly target the androgen receptor. A novel microtubule-targeted
      agent, cabazitaxel, has demonstrated an overall survival benefit following
      progression on docetaxel. Other agents target tumor immunogenicity and immune
      checkpoint pathways to attempt to harness the host immune system. The recently
      approved radiopharmaceutical, radium-223 dichloride, has demonstrated impressive
      results in patients with extensive bony metastases with minimal toxicity. Lastly,
      further understanding of the pathways underlying CRPC progression has led to late
      phase clinical trials with the novel agents: custirsen, tasquinimod and
      cabozantinib. This article reviews the approved therapies for CRPC, the agents
      currently in late-phase clinical trials, and notable early-phase trials of novel
      therapies and their combinations, with particular attention to trials
      incorporating novel biomarkers and intermediate endpoints to better identify
      those men who may or may not benefit from specific therapies. 

PMID- 25057304
TI  - Isolated hepatic perfusion for patients with liver metastases.
AB  - Up to 80% of colorectal, melanoma, and neuroendocrine liver metastases are
      unresectable due to excessive tumor burden. Isolated hepatic perfusion (IHP)
      administers intensive therapy to the liver while limiting systemic toxicity and
      thus may have an important role in the management of unresectable liver
      metastases. This review s describes the development of IHP, initial clinical
      results, open and percutaneous IHP techniques, and contemporary long-term
      treatment outcomes. IHP with melphalan or tumor necrosis factor alpha (TNFalpha)
      has been shown to achieve hepatic response rates of greater than 50% with
      progression-free survival of greater than 12 months among patients with
      refractory ocular melanoma liver metastases. The only series describing outcomes
      of IHP for neuroendocrine liver metastases notes an overall response rate of 50%
      and a median actuarial overall survival of 48 months after IHP treatment with
      melphalan or TNFalpha. The majority of studies that have evaluated IHP have been
      performed in patients with colorectal cancer liver metastases (CRCLM). In
      aggregate, survival results from retrospective studies and phase I/II clinical
      trials suggest that IHP demonstrated no significant survival benefit compared
      with systemic chemotherapy alone as first-line therapy. In contrast, IHP does
      improve outcomes relative to that provided by second-line chemotherapy for CRCLM,
      with overall response rates of 60% and median duration of liver response of 12
      months. Continued evaluation of IHP for unresectable liver metastases is
      necessary to establish its role in multidisciplinary treatment approaches. 

PMID- 25057305
TI  - FGF10: Type III Epithelial Mesenchymal Transition and Invasion in Breast Cancer
      Cell Lines.
AB  - PURPOSE: Fibroblastic growth factor-10 (FGF-10) has an important role in type I
      epithelial mesenchymal transition (EMT) during the embryonic period of life
      (gastrulation). Since EMT has a critical role during cancer cells invasion and
      metastasis (type III) this study sought to investigate the possible role of FGF
      10 in type III EMT by monitoring breast cancer cell lines' behavior by FGF-10
      regulation. METHODS: MCF-7 and MDA-MB-231 cell lines with different levels of
      FGF10 expression were treated with FGF-10 recombinant protein and FGF-10 siRNA,
      respectively. RESULTS: The cell viability, migration, colony formation and wound
      healing have a direct relationship with FGF-10 expression, while FGF-10
      expression decreased apoptosis. All mesenchymal factors (such as vimentin, N
      cadherin, snail, slug, TGF-beta) increased due to FGF-10 expression with contrary
      expression of epithelial markers (such as E-cadherin). Moreover, GSK3beta
      phosphorylation (inactivation) increased with FGF-10 expression. CONCLUSION: The
      important role of FGF-10 in type III EMT on cancer cells and initiation of
      metastasis via various kinds of signaling pathways has been suggested.

PMID- 25057306
TI  - Metastatic hepatocarcinoma he/de tumor model in rat.
AB  - The aim of this study is to select among potential tumor models that could be
      suitable to follow the metastatic spead of tumor cells. (18)FDG-PET tumor
      diagnostic test has been adapted to investigate tumor growth in vivo in local and
      metastatic rat models. Materials and Methods. The expression of glucose
      transporters was traced by immunohistological analysis, followed by the uptake of
      (18)FDG and visualized by MiniPET scanner. After s.c. administration of
      hepatocarcinoma (He/De) cells intensive local tumor growth and (18)FDG uptake
      were measured. RESULTS: Whole body (18)FDG-PET imaging supported by histological
      analysis have shown that subcutaneously growing tumors did not project metastases
      to other sites from the injected area. To avoid local tumor formation i.v.
      injection was chosen, but did not improve the safety of tumor cell
      administration. Tumor formation after i.v. injection took a longer time than
      after s.c. administration. Tumors upon i.v. generation were smaller and
      detectable in liver and lung, but not in other organs or tissues. iii) Subrenally
      implanted He/De cells spread from the retroperitoneal primary tumor of the kidney
      to thoracal paratymic lymph nodes (PTNs). The spread from primary site to
      metastatic tumors in PTNs was confirmed by post mortem surgery and histological
      examinations. CONCLUSION: Among the three methods applied: a) Local s.c.
      administration of tumor cells generated local tumors unsuitable to study
      metastasis. b) Intravenous administration causing unpredicatable location of
      tumor formation is not regarded a reliable metastatic tumor model. c) Subreanal
      implantation model proved to be a suitable model to follow the metastatic process
      in rats.

PMID- 25057309
TI  - 3.0T MR-CAD: Clinical Value in Diagnosis of Breast Tumor Compared with
      Conventional MRI.
AB  - PURPOSE: to explore the clinical value of 3.0T magnetic resonance (MR) imaging
      compared with computer-aided MR diagnosis (MR-CAD) in differential diagnosis of
      benign and malignant breast tumors. MATERIALS AND METHODS: MRI method and MR-CAD
      method was used in the diagnosis of a total of 93 breast lesions of 78 patients,
      based on the morphological and time-intensity-curve (TIC) analysis. The accuracy
      of the two modalities in differentiating malignant and benign breast tumor was
      compared. RESULTS: MR-CAD method yielded a statistically better accuracy than MRI
      method. For 51 mass-like lesions, MRI and MR-CAD had no difference in diagnosing
      accuracy, but MR-CAD had better accuracy in 42 non-mass-like lesions. CONCLUSION:
      MR-CAD had a notable advantage over MRI in differential diagnosis of benign and
      malignant breast tumors, especially non-mass-like tumor.

PMID- 25057308
TI  - Characterization of cancer stem-like cells derived from mouse induced pluripotent
      stem cells transformed by tumor-derived extracellular vesicles.
AB  - Several studies have shown that cancer niche can perform an active role in the
      regulation of tumor cell maintenance and progression through extracellular
      vesicles-based intercellular communication. However, it has not been reported
      whether this vesicle-mediated communication affects the malignant transformation
      of normal stem cells/progenitors. We have previously reported that the
      conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line
      can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells
      (CSCs), indicating that normal stem cells when placed in an aberrant
      microenvironment can give rise to functionally active CSCs. Here, we focused on
      the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted
      from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs
      from the conditioned medium of LLC cells, and then the differentiating miPSCs
      were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev)
      expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere
      formation of the miPS-LLCev cells in suspension culture indicated that the self
      renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev
      cells were subcutaneously transplanted into Balb/c nude mice, malignant
      liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS
      LLCevDT, the cells established from primary site and disseminated liposarcomas,
      respectively, showed their capacities to self-renew and differentiate into
      adipocytes and endothelial cells. Moreover, we confirmed the secondary
      liposarcoma development when these cells were transplanted. Taken together, these
      results indicate that miPS-LLCev cells possess CSC properties. Thus, our current
      study provides the first evidence that tEVs have the potential to induce CSC
      properties in normal tissue stem cells/progenitors. 

PMID- 25057310
TI  - Transcatheter arterial chemoembolization for intermediate-stage hepatocellular
      carcinoma: clinical outcome and safety in elderly patients.
AB  - AIM: The aim of our study was to compare clinical outcomes between elderly
      patients aged >=75 years (elderly group, n=66) with intermediate hepatocellular
      carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE) and
      younger patients aged <75 years (control group, n=84) with intermediate HCC
      undergoing TACE. METHODS: Clinical outcomes, including overall survival (OS) and
      tumor response rate at initial therapy, were compared between these two groups.
      RESULTS: The median survival time and the 1- and 3-year cumulative OS rates were
      2.90 years and 84.1% and 48.0%, respectively, in the elderly group and 2.44 years
      and 78.2% and 39.3%, respectively, in the control group (p=0.887). The objective
      response rate in the elderly group was 81.8% (54/66 patients), while that in the
      control group was 78.6% (66/84 patients) (p=0.227). CONCLUSION: Elderly patients
      with intermediate HCC undergoing TACE had a prognosis comparable with that of
      younger patients with intermediate HCC undergoing TACE.

PMID- 25057307
TI  - Far beyond the usual biomarkers in breast cancer: a review.
AB  - Research investigating biomarkers for early detection, prognosis and the
      prediction of treatment responses in breast cancer is rapidly expanding. However,
      no validated biomarker currently exists for use in routine clinical practice, and
      breast cancer detection and management remains dependent on invasive procedures.
      Histological examination remains the standard for diagnosis, whereas
      immunohistochemical and genetic tests are utilized for treatment decisions and
      prognosis determinations. Therefore, we conducted a comprehensive review of
      literature published in PubMed on breast cancer biomarkers between 2009 and 2013.
      The keywords that were used together were breast cancer, biomarkers, diagnosis,
      prognosis and drug response. The cited references of the manuscripts included in
      this review were also screened. We have comprehensively summarized the
      performance of several biomarkers for diagnosis, prognosis and predicted drug
      responses of breast cancer. Finally, we have identified 15 biomarkers that have
      demonstrated promise in initial studies and several miRNAs. At this point, such
      biomarkers must be rigorously validated in the clinical setting to be translated
      into clinically useful tests for the diagnosis, prognosis and prediction of drug
      responses of breast cancer. 

PMID- 25057311
TI  - Newly Identified Cancer-Associated Role of Human Neuronal Growth Regulator 1
      (NEGR1).
AB  - Neuronal growth regulator 1 (NEGR1) has become a great interest based on the
      recent findings that its genetic alteration is implicated in human obesity and
      human dyslexia. By analyzing the gene expression profiles of tumor biopsies and
      normal tissues, we identified NEGR1 as a commonly down-regulated gene in many
      types of human cancer tissues. NEGR1 contains a C-terminal GPI anchor attachment
      site and is primarily localized to cell membrane rafts, especially in cell-to
      cell contacting areas. The oncogenic phenotype was clearly attenuated when NEGR1
      was overexpressed in the human ovarian cancer cell line SKOV-3. Furthermore, cell
      aggregation and neurite outgrowth was greatly increased by NEGR1 overexpression.
      On the contrary, cell migration and invasion was increased in NEGR1-depleted
      cells, suggesting that NEGR1 may contribute to tumor suppression. Taken together,
      we suggest that NEGR1 is a raft-associated extracellular protein that may
      participate in cell recognition and interaction, which is important in growth
      control and malignant transformation. 

PMID- 25057312
TI  - Mn-porphyrin conjugated Au nanoshells encapsulating doxorubicin for potential
      magnetic resonance imaging and light triggered synergistic therapy of cancer.
AB  - A theranostic agent was successfully fabricated by the formation of Au nanoshell
      around poly(lactic acid) nanoparticles entrapping doxorubicin, followed by
      linking a Mn-porphyrin derivative on the Au shell surface through polyethylene
      glycol. The resulted agent exhibited excellent colloidal stability and long blood
      circulation time due to introducing polyethylene glycol. The grafting Mn
      porphyrin onto the nanoparticle surface endowed a greatly improved relaxivity (r1
      value of 22.18 mM(-1)s(-1) of Mn(3+)), favorable for accurate cancer diagnosing
      and locating the tumor site to guide the external near infrared (NIR) laser
      irradiation for photothermal ablation of tumors. The in vitro experiments
      confirmed that the agent exhibited an efficient photohyperthermia and a light
      triggered and stepwise release behavior of doxorubicin due to the high NIR light
      absorption coefficient of Au nanoshell. The in vivo experiments showed that the
      combination of chemotherapy and photothermal therapy through such theranostic
      agent offered a synergistically improved therapeutic outcome compared with either
      therapy alone, making it a promising approach for cancer therapy. Therefore, such
      theranostic agent can be developed as a smart and promising nanosystemplatform
      that integrates multiple capabilities for both effective contrast enhanced
      magnetic resonance imaging and synergistic therapy. 

PMID- 25057313
TI  - Nanoparticle-mediated systemic delivery of siRNA for treatment of cancers and
      viral infections.
AB  - RNA interference (RNAi) is an endogenous post-transcriptional gene regulatory
      mechanism, where non-coding, double-stranded RNA molecules interfere with the
      expression of certain genes in order to silence it. Since its discovery, this
      phenomenon has evolved as powerful technology to diagnose and treat diseases at
      cellular and molecular levels. With a lot of attention, short interfering RNA
      (siRNA) therapeutics has brought a great hope for treatment of various
      undruggable diseases, including genetic diseases, cancer, and resistant viral
      infections. However, the challenge of their systemic delivery and on how they are
      integrated to exhibit the desired properties and functions remains a key
      bottleneck for realizing its full potential. Nanoparticles are currently well
      known to exhibit a number of unique properties that could be strategically
      tailored into new advanced siRNA delivery systems. This review summarizes the
      various nanoparticulate systems developed so far in the literature for systemic
      delivery of siRNA, which include silica and silicon-based nanoparticles, metal
      and metal oxides nanoparticles, carbon nanotubes, graphene, dendrimers, polymers,
      cyclodextrins, lipids, hydrogels, and semiconductor nanocrystals. Challenges and
      barriers to the delivery of siRNA and the role of different nanoparticles to
      surmount these challenges are also included in the review. 

PMID- 25057314
TI  - An EGFR targeted PET imaging probe for the detection of colonic adenocarcinomas
      in the setting of colitis.
AB  - Colorectal cancer is a serious complication associated with inflammatory bowel
      disease, often indistinguishable by screening with conventional FDG PET probes.
      We have developed an alternative EGFR-targeted PET imaging probe that may be used
      to overcome this difficulty, and successfully assessed its utility for neoplastic
      lesion detection in preclinical models. Cetuximab F(ab')2 fragments were
      enzymatically generated, purified, and DOTA-conjugated. Radiolabeling was
      performed with (67)Ga for cell based studies and (64)Cu for in vivo imaging.
      Competitive binding studies were performed on CT26 cells to assess affinity (KD)
      and receptors per cell (Bmax). In vivo imaging using the EGFR targeted PET probe
      and (18)F FDG was performed on CT26 tumor bearing mice in both control and
      dextran sodium sulfate (DSS) induced colitis settings. Spontaneous adenomas in
      genetically engineered mouse (GEM) models of colon cancer were additionally
      imaged. The EGFR imaging agent was generated with high purity (> 98%), with a
      labeling efficiency of 60 +/- 5% and >=99% radiochemical purity. The KD was 6.6
      +/- 0.7 nM and the Bmax for CT26 cells was 3.3 +/- 0.1 * 10(6) receptors/cell.
      Target to background ratios (TBR) for CT26 tumors compared to colonic uptake
      demonstrated high values for both (18)F-FDG (3.95 +/- 0.13) and the developed
      (64)Cu-DOTA-cetuximab-F(ab')2 probe (4.42 +/- 0.11) in control mice. The TBR for
      the EGFR targeted probe remained high (3.78 +/- 0.06) in the setting of colitis,
      while for (18)F FDG, this was markedly reduced (1.54 +/- 0.08). Assessment of the
      EGFR targeted probe in the GEM models demonstrated a correlation between
      radiotracer uptake in spontaneous colonic lesions and the EGFR staining level ex
      vivo. A clinically translatable PET imaging probe was successfully developed to
      assess EGFR. The imaging agent can detect colonic tumors with a high TBR for
      detection of in situ lesions in the setting of colitis, and opens the possibility
      for a new approach for screening high-risk patients. 

PMID- 25057315
TI  - Theranostic self-assembly structure of gold nanoparticles for NIR photothermal
      therapy and X-Ray computed tomography imaging.
AB  - The controllable self-assembly of amphiphilic mixed polymers grafted gold
      nanoparitcles (AuNPs) leads to strong interparticle plasmonic coupling, which can
      be tuned to the near-infrared (NIR) region for enhanced photothermal therapy
      (PTT). In this study, an improved thiolation method was adopted for ATRP and ROP
      polymer to obtain amphiphilic brushes of PMEO2MA-SH and PCL-SH. By anchoring PCL
      SH and PMEO2MA-SH onto the 14 nm AuNPs, a smart hybrid building block for self
      assembly was obtained. Increasing the PCL/PMEO2MA chain ratio from 0.8:1, 2:1 and
      3:1 to 7:1, the structure of gold assemblies (GAs) was observed to transfer from
      vesicle to large compound micelle (LCM). Contributed to the special dense packed
      structure of gold nanoparticles in LCM, the absorption spectrometry of gold
      nanoparticles drastically red-shifted from 520 nm to 830 nm, which endowed the
      GAs remarkable NIR photothermal conversion ability. In addition, gold has high X
      ray absorption coefficient which qualifies gold nanomaterial a potential CT
      contrast agent Herein, we obtain a novel gold assembly structure which can be
      utilized as potential photothermal therapeutic and CT contrast agents. In vitro
      and In vivo studies testified the excellent treatment efficacy of optimum GAs as
      a PTT and CT contrast agent. In vitro degradation test, MTT assay and histology
      study indicated that GAs was a safe, low toxic reagent with good
      biodegradability. Therefore, the optimum GAs with strong NIR absorption and high
      X-ray absorption coefficient could be used as a theranostic agent and the
      formation of novel gold large compound micelle might offers a new theory
      foundation for engineering design and synthesis of polymer grafted AuNPs for
      biomedical applications. 

PMID- 25057316
TI  - Immuno nanoparticles integrated electrical control of targeted cancer cell
      development using whole cell bioelectronic device.
AB  - Electrical properties of cells determine most of the cellular functions,
      particularly ones which occur in the cell's membrane. Manipulation of these
      electrical properties may provide a powerful electrotherapy option for the
      treatment of cancer as cancerous cells have been shown to be more electronegative
      than normal proliferating cells. Previously, we used an electrical impedance
      sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal
      HUVEC cells to low intensity (<2 V/cm) AC electric fields, determining that the
      optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the
      non-cancerous HUVECs. In this study, to determine if these effects are cell type
      dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of
      frequencies (50 kHz-2 MHz) similar to the previously tested SKOV3. For the MCF7,
      an optimal frequency of 100 kHz was determined using the EIS, indicating a higher
      sensitivity towards the applied field. Further experiments specifically targeting
      the two types of cancer cells using HER2 antibody functionalized gold
      nanoparticles (HER2-AuNPs) were performed to determine if enhanced electric field
      strength can be induced via the application of nanoparticles, consequently
      leading to the killing of the cancerous cells without affecting non cancerous
      HUVECs and MCF10a providing a platform for the development of a non-invasive
      cancer treatment without any harmful side effects. The EIS was used to monitor
      the real-time consequences on cellular viability and a noticeable decrease in the
      growth profile of the MCF7 was observed with the application of the HER2-AuNPs
      and the electric fields indicating specific inhibitory effects on dividing cells
      in culture. To further understand the effects of the externally applied field to
      the cells, an Annexin V/EthD-III assay was performed to determine the cell death
      mechanism indicating apoptosis. The zeta potential of the SKOV3 and the MCF7
      before and after incorporation of the HER2-AuNPs was also obtained indicating a
      decrease in zeta potential with the incorporation of the nanoparticles. The
      outcome of this research will improve our fundamental understanding of the
      behavior of cancer cells and define optimal parameters of electrotherapy for
      clinical and drug delivery applications. 

PMID- 25057317
TI  - Progress in aptamer-mediated drug delivery vehicles for cancer targeting and its
      implications in addressing chemotherapeutic challenges.
AB  - Aptamers are novel oligonucleotides with flexible three-dimensional
      configurations that recognize and bind to their cognate targets, including tumor
      surface receptors, in a high-affinity and highly specific manner. Because of
      their unique intrinsic properties, a variety of aptamer-mediated nanovehicles
      have been developed to directionally transport anti-cancer drugs to tumor sites
      to minimize systemic cytotoxicity and to enhance permeation by these tumoricidal
      agents. Despite advances in the selection and synthesis of aptamers and in the
      conjugation and self-assembly of nanotechnologies, current chemotherapy and drug
      delivery systems face great challenges. These challenges are due to the
      limitations of aptamers and vehicles and because of complicated tumor mechanisms,
      including heterogeneity, anti-cancer drug resistance, and hypoxia-induced
      aberrances. In this review, we will summarize current approaches utilizing tumor
      surface hallmarks and aptamers and their roles and mechanisms in therapeutic
      nanovehicles targeting tumors. Delivery forms include nanoparticles, nanotubes,
      nanogels, aptamer-drug conjugates, and novel molecular trains. Moreover, the
      obstacles posed by the aforementioned issues will be highlighted, and possible
      solutions will be acknowledged. Furthermore, future perspectives will be
      presented, including cutting-edge integration with RNA interference
      nanotechnology and personalized chemotherapy, which will facilitate innovative
      approaches to aptamer-based therapeutics. 

PMID- 25057318
TI  - Specific and sensitive tumor imaging using biostable oligonucleotide aptamer
      probes.
AB  - Although several imaging modalities are widely used for tumor imaging, none are
      tumor type-specific. Different types of cancer exhibit differential therapeutic
      responses, thus necessitating development of an imaging modality able to detect
      various tumor types with high specificity. To illustrate this point, CD30
      specific oligonucleotide aptamer in vivo imaging probes were conjugated to the
      near-infrared IRD800CW reporter. Mice bearing xenografted CD30-positive or
      control CD30-negative lymphoma tumors on contralateral sides of the same mouse
      were developed. Following a systemic administration of aptamer probes, whole body
      imaging of tumor-bearing mice was performed. Imaging signal from tumor sites was
      analyzed and imaging specificity confirmed by tissue immunostaining. The in vivo
      biodistribution of aptamer probes was also evaluated. Whole body scans revealed
      that the RNA-based aptamer probes selectively highlighted CD30-expressing
      lymphoma tumors immediately after systemic administration, but did not react with
      control tumors in the same mouse. The resultant imaging signal lasted up to 1 hr
      and the aptamer probes were rapidly eliminated from the body through urinary and
      lower intestinal tracts. For more sensitive imaging, biostable CD30-specific
      ssDNA-based aptamer probes were also generated. Systemic administration of these
      probes also selectively highlighted the CD30-positive lymphoma tumors, with
      imaging signal detected 4-5 folds higher than that derived from control tumors in
      the same animal, and lasted for up to 24hr. This study demonstrates that
      oligonucleotide aptamer probes can provide tumor type-specific imaging with high
      sensitivity and a long-lasting signal, indicating their potential for clinical
      applications. 

PMID- 25057320
TI  - Meta-analysis of candidate gene effects using bayesian parametric and non
      parametric approaches.
AB  - Candidate gene (CG) approaches provide a strategy for identification and
      characterization of major genes underlying complex phenotypes such as production
      traits and susceptibility to diseases, but the conclusions tend to be
      inconsistent across individual studies. Meta-analysis approaches can deal with
      these situations, e.g., by pooling effect-size estimates or combining P values
      from multiple studies. In this paper, we evaluated the performance of two types
      of statistical models, parametric and non-parametric, for meta-analysis of CG
      effects using simulated data. Both models estimated a "central" effect size while
      taking into account heterogeneity over individual studies. The empirical
      distribution of study-specific CG effects was multi-modal. The parametric model
      assumed a normal distribution for the study-specific CG effects whereas the non
      parametric model relaxed this assumption by posing a more general distribution
      with a Dirichlet process prior (DPP). Results indicated that the meta-analysis
      approaches could reduce false positive or false negative rates by pooling
      strengths from multiple studies, as compared to individual studies. In addition,
      the non-parametric, DPP model captured the variation of the "data" better than
      its parametric counterpart. 

PMID- 25057319
TI  - Hair metabolomics: identification of fetal compromise provides proof of concept
      for biomarker discovery.
AB  - Analysis of the human metabolome has yielded valuable insights into health,
      disease and toxicity. However, the metabolic profile of complex biological fluids
      such as blood is highly dynamic and this has limited the discovery of robust
      biomarkers. Hair grows relatively slowly, and both endogenous compounds and
      environmental exposures are incorporated from blood into hair during growth,
      which reflects the average chemical composition over several months. We used hair
      samples to study the metabolite profiles of women with pregnancies complicated by
      fetal growth restriction (FGR) and healthy matched controls. We report the use of
      GC-MS metabolite profiling of hair samples for biomarker discovery. Unsupervised
      statistical analysis showed complete discrimination of FGR from controls based on
      hair composition alone. A predictive model combining 5 metabolites produced an
      area under the receiver-operating curve of 0.998. This is the first study of the
      metabolome of human hair and demonstrates that this biological material contains
      robust biomarkers, which may lead to the development of a sensitive diagnostic
      tool for FGR, and perhaps more importantly, to stable biomarkers for a range of
      other diseases. 

PMID- 25057321
TI  - Analysis of diversity and linkage disequilibrium mapping of agronomic traits on B
      genome of wheat.
AB  - Association mapping is an efficient method to test the association between
      molecular markers and quantitative trait loci (QTL) based on linkage
      disequilibrium (LD). In this study, 13 agronomic traits of 109 wheat accessions
      were evaluated at Tai'an of China in 2006-2010. Genetic diversity, population
      structure, and LD were investigated using Diversity Array Technology (DArT)
      markers. The extent of LD on B-genome (chromosomes 1B, 2B, 3B, 4B, 5B, 6B and 7B)
      was about 18-27 cM. The polymorphism information content (PIC) value of markers
      in the LD blocks was often lower than the mean value of each chromosome. Analysis
      of the phenotypic diversity of the 13 traits showed that the population structure
      accounted for an average of 5.82% of the phenotypic variation. Association of 139
      DArT markers on chromosome 1B-7B with the 13 traits was analyzed with a mixed
      linear model. A total of 84 significant marker trait associations (MTAs) were
      found and some of the associated markers were located in the QTL region detected
      in previous linkage mapping studies. Combined with hitchhiking effects, we
      identified five important markers for future analysis, such as wPt-1708(4B,
      93.8cM), wPt-3457(5B, 92.3cM), wPt-9613(5B, 94.4cM), wPt-4858(6B, 66.1cM) and wPt
      8598(7B, 142.4cM). The information obtained in this study should be useful for
      marker-assisted selection in wheat breeding programs. 

PMID- 25057323
TI  - Renin gene polymorphisms in bangladeshi hypertensive population.
AB  - OBJECTIVE: Linkages of renin gene polymorphisms with hypertension have been
      implicated in several populations with contrasting results. Present study aims to
      assess the pattern of renin gene polymorphisms in Bangladeshi hypertensive
      individuals. METHODOLOGY: Introns 1, 9 of renin gene and 4063 bases upstream of
      promoter sequence of renin gene were amplified from the genomic DNA of the total
      124 (hypertensive and normotensive) subjects using respective primers. Polymerase
      chain reaction-based restriction fragment length polymorphisms were performed
      using BglI, MboI and TaqI restriction enzymes. RESULTS: Homozygosity was common
      in renin gene regarding BglI (bb=48.4%, Bb=37.9%, BB=13.7%, chi (2) =1.91,
      P>0.05), TaqI (TT=81.5%, Tt=14.5%, tt=4.0%, chi (2) =7.50, P<0.01) and MboI
      (mm=63.7%, Mm=32.3%, MM=4.0%, chi (2) =0.00, P>0.05) polymorphisms among total
      study population. For BglI and TaqI genotype distribution, hypertensive subjects
      (BglI: chi (2) =6.66, P<0.05; TaqI: chi (2) = 10.28, P<0.005) significantly
      deviate from Hardy-Weinberg Equilibrium law compared to normotensive subjects
      (BglI: chi (2) =0.51, P>0.05; TaqI: chi (2) =0.20, P>0.05). On the other hand,
      with respect to MboI polymorphisms of renin gene, only normotensive subjects
      deviate from the law (patients: chi (2) =1.28, P>0.05; vs controls: chi (2)
      =6.81, P<0.01). In the context of allelic frequency, common T allele was clearly
      prevalent (T frequency=0.86, t frequency = 0.14) for TaqI, but rare alleles b and
      m were more frequent for both BglI (b frequency=0.69, B frequency=0.31) and MboI
      (m frequency=0.80 M frequency=0.20) polymorphisms, respectively. CONCLUSION:
      Thus, we report that Bangladeshi hypertensive subjects did not show any distinct
      pattern of renin gene polymorphisms compared to their healthy control subjects
      with regard to their genotypic and allelic frequencies.

PMID- 25057324
TI  - No Variation at 29 Microsatellites in the Genome of Jatropha curcas.
AB  - Genetic variation in the genome of a given species is the basis for natural
      selection and genetic improvement through selective breeding. We applied 29
      microsatellites located on 11 linkage groups to study genetic variation in 276
      accessions of J. curcas collected from nine locations in five countries in South
      America, Asia and Africa to initiate a breeding program. To our surprise, we did
      not detect any genetic diversity at all 29 microsatellites loci. All the 276
      accessions were homozygous at all loci and shared the same genotype at each
      locus, suggesting no microsatellite variation in the genome of Jatropha curcas.
      This result is quite unusual, and may have a profound influence on the breeding
      strategies and genome study of this species. 

PMID- 25057322
TI  - Molecular heterogeneities of adipose depots - potential effects on adipose-muscle
      cross-talk in humans, mice and farm animals.
AB  - Adipose tissue is considered as a major endocrine organ that secretes numerous
      proteins called adipokines. The heterogeneous nature of adipose tissue in
      different parts of the body suggests respective heterogeneity of proteomes and
      secretomes. This review consolidates knowledge from recent studies targeting the
      diversity of different adipose depots affecting the pattern of secreted
      adipokines and discusses potential consequences for the cross-talk between
      adipose and skeletal muscle in humans, rodent models and farm animals. Special
      attention is paid to muscle-associated fat depots like inter- and intramuscular
      fat that become focus of attention in the context of the rather new notion of
      skeletal muscle as a major endocrine organ. Understanding the complexity of
      communication between adipocytes and skeletal muscle cells will allow developing
      strategies for improvement of human health and for sustainable production of high
      quality meat. 

PMID- 25057325
TI  - How do y-chromosomes modulate genome-wide epigenetic States: genome folding,
      chromatin sinks, and gene expression.
AB  - The Y chromosomes of Drosophila melanogaster and D. simulans contain only a
      handful of protein-coding genes, which are related to sperm mobility and
      reproductive fitness. Despite low or absent protein coding polymorphism, the
      Drosophila Y chromosome has been associated with natural phenotypic variation,
      including variation in the expression of hundreds to thousands of genes located
      on autosomes and on the X chromosome. Polymorphisms present in the large blocks
      of heterochromatin and consisting of differences in the amounts and kinds of
      sequences for satellite DNA and transposable elements may be the source of this
      modulation. Here we review the evidence and discuss mechanisms for global
      epigenetic regulation by repetitious elements in the Y chromosome. We also
      discuss how the discovery of this new function impacts the current knowledge
      about Y chromosome origin, its current dynamics, and future fate. 

PMID- 25057327
TI  - Draft Genome Sequence of the Extremely Halophilic Phototrophic Purple Sulfur
      Bacterium Halorhodospira halochloris.
AB  - Halorhodospira halochloris is an extremely halophilic bacterium isolated from
      hypersaline Wadi Nantrun lakes in Egypt. Here we report the draft genome sequence
      of this gammaproteobacteria (GI number: 589289709, GenBank Accession number:
      CP007268). The 3.5-Mb genome encodes for photosynthesis and biosynthesis of
      organic osmoprotectants. Comparison with the genome of H.halophila promises to
      yield insights into the evolution of halophilic adaptations. 

PMID- 25057326
TI  - Meiotic sex chromosome inactivation in Drosophila.
AB  - In several different taxa, there is indubitable evidence of transcriptional
      silencing of the X and Y chromosomes in male meiotic cells of spermatogenesis.
      However, the so called meiotic sex chromosome inactivation (MSCI) has been
      recently a hot bed for debate in Drosophila melanogaster. This review covers
      cytological and genetic observations, data from transgenic constructs with testis
      specific promoters, global expression profiles obtained from mutant, wild-type,
      larvae and adult testes as well as from cells of different stages of
      spermatogenesis. There is no dispute on that D. melanogaster spermatogenesis
      presents a down-regulation of X chromosome that does not result from the lack of
      dosage compensation. However, the issue is currently focused on the level of
      reduction of X-linked expression, the precise time it occurs and how many genes
      are affected. The deep examination of data and experiments in this review exposes
      the limitations intrinsic to the methods of studying MSCI in D. melanogaster. The
      current methods do not allow us to affirm anything else than the X chromosome
      down-regulation in meiosis (MSCI). Therefore, conclusion about level, degree or
      precise timing is inadequate until new approaches are implemented to know the
      details of MSCI or other processes involved for D. melanogaster model. 

PMID- 25057328
TI  - Genetic contributions to visuospatial cognition in Williams syndrome: insights
      from two contrasting partial deletion patients.
AB  - BACKGROUND: Williams syndrome (WS) is a rare neurodevelopmental disorder arising
      from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus
      7q11.23. WS is characterised by an uneven cognitive profile, with serious
      deficits in visuospatial tasks in comparison to relatively proficient performance
      in some other cognitive domains such as language and face processing. Individuals
      with partial genetic deletions within the WS critical region (WSCR) have provided
      insights into the contribution of specific genes to this complex phenotype.
      However, the combinatorial effects of different genes remain elusive. METHODS: WE
      REPORT ON VISUOSPATIAL COGNITION IN TWO INDIVIDUALS WITH CONTRASTING PARTIAL
      DELETIONS IN THE WSCR: one female (HR), aged 11 years 9 months, with
      haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB),
      aged 14 years 2 months, with the three most telomeric genes within the WSCR
      deleted, or partially deleted. RESULTS: Our in-depth phenotyping of the
      visuospatial domain from table-top psychometric, and small- and large-scale
      experimental tasks reveal a profile in HR in line with typically developing
      controls, albeit with some atypical features. These data are contrasted with
      patient JB's atypical profile of strengths and weaknesses across the visuospatial
      domain, as well as with more substantial visuospatial deficits in individuals
      with the full WS deletion. CONCLUSIONS: Our findings point to the contribution of
      specific genes to spatial processing difficulties associated with WS,
      highlighting the multifaceted nature of spatial cognition and the divergent
      effects of genetic deletions within the WSCR on different components of
      visuospatial ability. The importance of general transcription factors at the
      telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial
      phenotype are also discussed.

PMID- 25057329
TI  - The neural correlates of visuo-spatial working memory in children with autism
      spectrum disorder: effects of cognitive load.
AB  - BACKGROUND: Research on the neural bases of cognitive deficits in autism spectrum
      disorder (ASD) has shown that working memory (WM) difficulties are associated
      with abnormalities in the prefrontal cortex. However, cognitive load impacts
      these findings, and no studies have examined the relation between WM load and
      neural underpinnings in children with ASD. Thus, the current study determined the
      effects of cognitive load on WM, using a visuo-spatial WM capacity task in
      children with and without ASD with functional magnetic resonance imaging (fMRI).
      METHODS: We used fMRI and a 1-back colour matching task (CMT) task with four
      levels of difficulty to compare the cortical activation patterns associated with
      WM in children (7-13 years old) with high functioning autism (N = 19) and matched
      controls (N = 17) across cognitive load. RESULTS: Performance on CMT was
      comparable between groups, with the exception of one difficulty level. Using
      linear trend analyses, the control group showed increasing activation as a
      function of difficulty level in frontal and parietal lobes, particularly between
      the highest difficulty levels, and decreasing activation as a function of
      difficulty level in the posterior cingulate and medial frontal gyri. In contrast,
      children with ASD showed increasing activation only in posterior brain regions
      and decreasing activation in the posterior cingulate and medial frontal gyri, as
      a function of difficulty level. Significant differences were found in the
      precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where
      control children showed greater positive linear relations between cortical
      activity and task difficulty level, particularly at the highest difficulty
      levels, but children with ASD did not show these trends. CONCLUSIONS: Children
      with ASD showed differences in activation in the frontal and parietal lobes-both
      critical substrates for visuo-spatial WM. Our data suggest that children with ASD
      rely mainly on posterior brain regions associated with visual and lower level
      processing, whereas controls showed activity in frontal lobes related to the
      classic WM network. Findings will help guide future work by localizing areas of
      vulnerability to developmental disturbances.

PMID- 25057330
TI  - Men and Their Father Figures: Exploring Racial and Ethnic Differences in Mental
      Health Outcomes.
AB  - Though gender, racial, and ethnic disparities in health in the United States are
      well documented, it is less clear how these factors intersect to produce patterns
      of mental health outcomes among men. This study examined the presence of father
      figures in the lives of African American, Caribbean black and non-Hispanic white
      American males until the age of 16; assessed the current socio-demographic
      factors of these men as adults; and explored whether these factors lead to
      variations in mental health outcomes. Regression models were used to examine the
      correlates of socio-demographic, psychosocial, and retrospective father figure
      measures for depressive symptoms and non-specific psychological distress among
      African American (n = 999), Caribbean black (n = 506), and non-Hispanic white men
      (n = 193) from the National Survey of American Life. Findings revealed racial and
      ethnic group differences by age, employment status, education, and household
      income on depressive symptoms (measured using the CES-D scale) and non-specific
      psychological distress (using the Kessler-6 scale). Findings suggested that being
      raised by a grandfather placed both African American and Caribbean black men at
      greater risk for depressive symptoms and non-specific psychological distress
      under certain socio-demographic conditions. This study is unique in that it
      considers the influence of father figures on the mental health outcomes of adult
      males across three racial and ethnic groups. We conclude with a discussion of the
      implications for future mental health research and practice with men of color.

PMID- 25057331
TI  - On the Relationship Between Neighborhood Perception, Length of Residence and Co
      Ethnic Concentration.
AB  - We investigate how co-ethnic concentration and length of residence are related to
      neighborhood perception in aged Mexican Americans, and discuss sources of
      information for measuring social environments. Neighborhood perception scale,
      length of residence in current home, and all individual-level covariates in a
      hierarchical linear model are derived from data on community-dwelling older
      adults. Tract-level measures are obtained from Census data. We find no
      relationship between co-ethnic concentration and positive neighborhood
      perception, and find a direct relationship between length of residence and
      positive neighborhood perception. Until further evidence is found, different
      sources of information when measuring place should be treated equally.

PMID- 25057332
TI  - The review of innovative integration of Kampo medicine and Western medicine as
      personalized medicine at the first multidisciplinary pain center in Japan.
AB  - BACKGROUND: The Japanese medical system is unique because it is the only country
      in the world where Western medicine and traditional Japanese medicine including
      Kampo medicine, traditional Japanese herbal medicine, are used in our daily
      clinical practice. Pain is essentially an interactive psychophysiological
      behavior pattern. Thus, an interdisciplinary approach is often recommended in
      providing appropriate therapeutic care for the patients suffering from chronic
      and intractable pain. In addition, we have been prescribing Kampo medicines in
      combination with Western medicines as personalized medicine in order to treat
      patients with chronic pain at our pain center. The aim of our study was to
      conduct a survey on the current use and the effect of Kampo medicines in our
      multidisciplinary pain center. METHODS: Retrospective analysis was performed on
      221 out of 487 patients suffering from chronic pain. RESULTS: The most frequent
      medical complaints for which Kampo medicines were prescribed were lower
      back/lower limb pain, neck/upper limb pain, various facial pains,
      headache/migraine, whiplash-associated disorder, and frozen shoulder. Kampo
      medicines were prescribed based on patient-centered Kampo diagnosis. Moreover,
      several Kampo medicines generally for the management of psychological symptoms
      were prescribed for about 70% of the patients. Pain improvement in the patients
      was categorized as follows: 26.3% with marked improvement, 12.7% with moderate
      improvement, 38.9% with some improvement, and 19.9% with no improvement.
      CONCLUSIONS: Two thirds of the chronic pain patients with the use of Kampo
      medicines combined with Western medicine experienced further pain improvements.

PMID- 25057333
TI  - The assessment of the role of baseline low-dose CT scan in patients at high risk
      of lung cancer.
AB  - BACKGROUND: Despite the progress in contemporary medicine comprising diagnostic
      and therapeutic methods, lung cancer is still one of the biggest health concerns
      in many countries of the world. The main purpose of the study was to evaluate the
      detection rate of pulmonary nodules and lung cancer in the initial, helical low
      dose CT of the chest as well as the analysis of the relationship between the size
      and the histopathological character of the detected nodules. MATERIAL/METHODS: We
      retrospectively evaluated 1999 initial, consecutive results of the CT
      examinations performed within the framework of early lung cancer detection
      program initiated in Szczecin. The project enrolled persons of both sexes, aged
      55-65 years, with at least 20 pack-years of cigarette smoking or current smokers.
      The analysis included assessment of the number of positive results and the
      evaluation of the detected nodules in relationship to their size. All of the
      nodules were classified into I of VI groups and subsequently compared with
      histopathological type of the neoplastic and nonneoplastic pulmonary lesions.
      RESULTS: Pulmonary nodules were detected in 921 (46%) subjects. What is more,
      malignant lesions as well as lung cancer were significantly, more frequently
      discovered in the group of asymptomatic nodules of the largest dimension
      exceeding 15 mm. CONCLUSIONS: The initial, low-dose helical CT of the lungs
      performed in high risk individuals enables detection of appreciable number of
      indeterminate pulmonary nodules. In most of the asymptomatic patients with
      histopathologically proven pulmonary nodules greater than 15 mm, the mentioned
      lesions are malignant, what warrants further, intensified diagnostics.

PMID- 25057334
TI  - GH3 tumor pituitary cell cytoskeleton and plasma membrane arrangement are
      determined by extracellular matrix proteins: implications on motility,
      proliferation and hormone secretion.
AB  - The extracellular matrix (ECM) influences different physiological and
      pathophysiological aspects of the cell. The ECM consists in a complex network of
      macromolecules with characteristic biochemical properties that allow cells to
      sense their environments inducing different signals and changing cell behavior.
      The purpose of the present study was to evaluate the participation of different
      ECM proteins in cell morphology and its implication on motility, proliferation
      and hormone secretion in GH3 cells, a tumor pituitary cell. GH3 cells were
      cultured with a defined medium on collagens I/III and IV, fibronectin and
      laminin. GH3 cells express alpha2 integrin subunit de novo. The cells responded
      to the ECM proteins with differentiated cell surface morphologies and membrane
      protrusions. A rounded shape with small membrane blebs, weak substrate adhesion
      and high motility was observed in cells on C I/III and fibronectin, while on C IV
      and laminin cells were viewed elongated and adhered. Differences on actin
      cytoskeleton, cytoskeletal-associated vinculin and phospho-MLC showed that ECM
      proteins determine the cytoskeleton organization. Cell proliferation showed
      dependency on the ECM protein, observing a higher rate in cells on collagen
      I/III. Prolactin secretion was higher in cells with small blebs, but an
      unchangeable response to EGF was obtained with the ECM proteins, suggesting is a
      consequence of cortical actin arrangement. We ascribe the functional differences
      of the GH3 cells to the cytoskeletal organization. Overall, the data showed that
      ECM plays a critical role in GH3 cells modulating different cellular comportment
      and evidenced the importance of the ECM composition of pituitary adenomas. 

PMID- 25057336
TI  - CD38 plays key roles in both antioxidation and cell survival of H2O2-treated
      primary rodent astrocytes.
AB  - CD38 is an ecto-enzyme that consumes NAD(+) to produce cyclic ADP-ribose (cADPR) 
      -- a potent agonist of ryanodine receptors. Recent studies have suggested CD38
      may play significant roles in both ischemic brain injury and traumatic brain
      injury, while the mechanisms underlying the roles of CD38 in neurological
      diseases remain unclear. Because oxidative stress plays key roles in both
      ischemic brain damage and traumatic brain damage, in this study we used primary
      astrocyte cultures as a experimental model to test our hypothesis that CD38 may
      play significant roles in oxidative stress-induced neural cell death. We found
      CD38 siRNA-produced decrease in CD38 levels can lead to a significant increase in
      H2O2-induced astrocyte death. Moreover, the CD38 siRNA treatment can
      significantly aggravate oxidative stress in the H2O2-treated cells, as indicated
      by increases in both superoxide and lipid peroxidation, suggesting that CD38 is
      required for maintaining the antioxidation capacity of the cells. We also found
      that H2O2 can induce increased CD38 expression. Collectively, our study has
      obtained novel findings suggesting that CD38 plays a significant role in both
      antioxidation and cell survival of reactive oxygen species-exposed primary
      astrocytes, suggesting that CD38 may become a novel target for decreasing the
      oxidative damage in neurological disorders. 

PMID- 25057337
TI  - Malate-aspartate shuttle mediates the intracellular ATP levels, antioxidation
      capacity and survival of differentiated PC12 cells.
AB  - NAD(+) and NADH play pivotal roles in numerous redox reactions in cells. While
      increasing evidence has indicated important roles of NAD(+) in cell survival and
      cellular functions, there has been distinct deficiency in the studies regarding
      the biological functions of NADH. NADH shuttles mediate the transfer of the
      reducing equivalents of the cytosolic NADH into mitochondria. Cumulating evidence
      has suggested that malate-aspartate shuttle (MAS), one of the two types of NADH
      shuttles, plays significant roles in multiple biological processes such as
      glutamate synthesis in neurons. Because there has been no information regarding
      the roles of NADH shuttle in the energy metabolism, antioxidation capacity, and
      survival of any type of neural cells, in this study we used differentiated PC12
      cells as a cellular model to investigate the roles of MAS in the energy
      metabolism, antioxidation capacity and survival of cells. We found that MAS
      inhibition led to a significant decrease in the levels of GSH - a major
      antioxidation molecule in cells, suggesting an important role of MAS in
      maintaining the antioxidation capacity of cells. Our study has also suggested
      that MAS could play critical roles in maintaining the intracellular ATP levels of
      the cells. Moreover, MAS inhibition was shown to significantly decrease the
      survival of differentiated PC12 cells. Collectively, our study has provided first
      evidence suggesting important roles of NADH shuttles in maintaining antioxidation
      capacity of cells. Our study has also suggested important roles of MAS in
      maintaining the intracellular ATP levels and survival of differentiated PC12
      cells. 

PMID- 25057335
TI  - The relationship between skeletal muscle mitochondrial citrate synthase activity
      and whole body oxygen uptake adaptations in response to exercise training.
AB  - Citrate synthase (CS) activity is a validated biomarker for mitochondrial density
      in skeletal muscle. CS activity is also used as a biochemical marker of the
      skeletal muscle oxidative adaptation to a training intervention, and a
      relationship between changes in whole body aerobic capacity and changes in CS
      activity is often assumed. However, this relationship and absolute values of CS
      and maximal oxygen uptake (V.O2max) has never been assessed across different
      studies. A systematic PubMed search on literature published from 1983 to 2013 was
      performed. The search profile included: citrate, synthase, human, skeletal,
      muscle, training, not electrical stimulation, not in-vitro, not rats. Studies
      that reported changes in CS activity and V.O2max were included. Different
      training types and subject populations were analyzed independently to assess
      correlation between relative changes in V.O2max and CS activity. 70 publications
      with 97 intervention groups were included. There was a positive (r = 0.45)
      correlation (P < 0.001) between the relative change in V.O2max and the relative
      change in CS activity. All reported absolute values of CS and V.O2max did not
      correlate (r =- 0.07, n = 148, P = 0.4). Training induced changes in whole body
      oxidative capacity is matched by changes in muscle CS activity in a nearly 1:1
      relationship. Absolute values of CS across different studies cannot be compared
      unless a standardized analytical method is used by all laboratories. 

PMID- 25057338
TI  - Urinary podocalyxin as a marker of preeclampsia in a Hispanic population.
AB  - BACKGROUND: Preeclampsia is associated with significant materno-fetal morbidity
      and mortality. Podocyturia due to podocyte damage seems to be associated with the
      disease. The objective of this study was to evaluate the usefulness of urinary
      podocalyxin as a marker of preeclampsia in a Hispanic population. METHODS: 63
      patients were studied. 25 patients had preeclampsia/eclampsia (PE-E). 38 patients
      had normal pregnancies and served as control group. 24 hour proteinuria, urine
      protein/creatinine (UPC), urinary podocalyxin and perinatal outcomes were
      measured. A Podocalyxin ELISA test was used to detect podocyturia. RESULTS: Mean
      age (years), mean+/-SD was 30.5+/-5.4 in normal patients vs 30.6+/-5.8 in PE-E,
      p=0.98. Median gestational age (weeks) was, 38 (range 21-42) for normal
      pregnancies and 36 (range 24-40) for patients with PE-E, <0.001. Urine
      podocalyxin/creatinine on admission (ng/mg), median [IQR] in normal patients was
      55.9 [29.4, 74.9] vs 109.7 [63.8, 234.1] in PE-E, p=0.001. After adjusting for
      admission proteinuria, urinary podocalyxin remained independently associated with
      preeclampsia: OR=1.0040 (95% CI 1.0003-1.0078), p=0.03. There was low to moderate
      correlation between UPC and urinary podocalyxin, Spearman's =0.31, p=0.01. In PE
      E, post-partum urine podocalyxin was lower, median [IQR]: 69.7 [32.7, 184.8]
      p=0.19 vs admission. There was a trend towards more podocyturia and proteinuria
      in patients with eclampsia, comparing to those with preeclampsia. There was no
      association observed between podocyturia and neonatal mortality, IUGR or Apgar
      scores. CONCLUSIONS: Significantly higher levels of urinary podocalyxin are seen
      in preeclampsia/eclampsia. They tend to normalize after delivery.

PMID- 25057340
TI  - Identification of a New RXRalpha Antagonist Targeting the Coregulator-Binding
      Site.
AB  - Retinoid X receptor-alpha (RXRalpha) is implicated in the regulation of many
      biological processes and also represents a unique intracellular target for
      pharmacologic interventions. Efforts on discovery of small molecules targeting
      RXRalpha have been primarily focused on the molecules that bind to its classical
      ligand-binding pocket (LBP). Here, we report the identification and
      characterization of a new RXRalpha transcriptional antagonist by using structure
      based virtual screening. The new antagonist binds with submicromolar affinity to
      RXRalpha (Kd = 4.88 * 10-7 M) and selectively inhibits RXRalpha transactivation.
      The compound does not bind to the LBP but to a hydrophobic groove on the surface
      of RXRalpha. The new compound also effectively suppresses AKT activation and
      promotes apoptosis of cancer cells in a RXRalpha-dependent manner by inhibiting
      tRXRalpha interaction with the p85alpha subunit of PI3K. Thus, the compound
      represents a new RXRalpha modulator that regulates the nongenomic actions of
      RXRalpha by surface binding.

PMID- 25057339
TI  - Active ingredients of ginger as potential candidates in the prevention and
      treatment of diseases via modulation of biological activities.
AB  - The current mode of treatment based on synthetic drugs is expensive and also
      causes genetic and metabolic alterations. However, safe and sound mode of
      treatment is needed to control the diseases development and progression. In this
      regards, medicinal plant and its constituents play an important role in diseases
      management via modulation of biological activities. Ginger, the rhizome of the
      Zingiber officinale, has shown therapeutic role in the health management since
      ancient time and considered as potential chemopreventive agent. Numerous studies
      based on clinical trials and animal model has shown that ginger and its
      constituents shows significant role in the prevention of diseases via modulation
      of genetic and metabolic activities. In this review, we focused on the
      therapeutics effects of ginger and its constituents in the diseases management,
      and its impact on genetic and metabolic activities. 

PMID- 25057341
TI  - MR to CT Registration of Brains using Image Synthesis.
AB  - Computed tomography (CT) is the standard imaging modality for patient dose
      calculation for radiation therapy. Magnetic resonance (MR) imaging (MRI) is used
      along with CT to identify brain structures due to its superior soft tissue
      contrast. Registration of MR and CT is necessary for accurate delineation of the
      tumor and other structures, and is critical in radiotherapy planning. Mutual
      information (MI) or its variants are typically used as a similarity metric to
      register MRI to CT. However, unlike CT, MRI intensity does not have an accepted
      calibrated intensity scale. Therefore, MI-based MR-CT registration may vary from
      scan to scan as MI depends on the joint histogram of the images. In this paper,
      we propose a fully automatic framework for MR-CT registration by synthesizing a
      synthetic CT image from MRI using a co-registered pair of MR and CT images as an
      atlas. Patches of the subject MRI are matched to the atlas and the synthetic CT
      patches are estimated in a probabilistic framework. The synthetic CT is
      registered to the original CT using a deformable registration and the computed
      deformation is applied to the MRI. In contrast to most existing methods, we do
      not need any manual intervention such as picking landmarks or regions of
      interests. The proposed method was validated on ten brain cancer patient cases,
      showing 25% improvement in MI and correlation between MR and CT images after
      registration compared to state-of-the-art registration methods.

PMID- 25057342
TI  - Editorial.

PMID- 25057343
TI  - Add-on clinical effects of simvastatin and ondansetron in patients with
      schizophrenia stabilized on antipsychotic treatment: pilot study.
AB  - OBJECTIVES: There is some evidence that anti-inflammatory treatment may have
      beneficial effects in schizophrenia and major depression. Statins are cholesterol
      lowering agents but have been found to be anti-inflammatory and also decrease C
      reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist
      widely used to prevent nausea and vomiting in patients receiving chemotherapy for
      cancer. Small studies have suggested that adjunctive ondansetron is efficacious
      against schizophrenia symptoms. We carried out a feasibility study in
      schizophrenia patients (within 5 years of first diagnosis) to explore the
      adjunctive use of simvastatin and ondansetron on positive, negative and general
      psychopathology. METHODS: This was a 12-week rater-blind placebo-controlled
      study. A total of 36 patients with DSM-IV diagnosis of schizophrenia were
      recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks
      using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression
      (CGI) scale, Global Assessment of Functioning (GAF) and Abnormal Involuntary
      Movement Scale (AIMS). RESULTS: Both simvastatin and ondansetron provide some
      evidence of a reduction in symptoms compared with treatment as usual (TAU) on
      PANSS total score, although this was not statistically significant. In the
      secondary analyses, no significant differences were seen on CGI, GAF and AIMS.
      CONCLUSIONS: Anti-inflammatory treatments have been shown to have some beneficial
      effects in schizophrenia. Both simvastatin and ondansetron provide some evidence
      of a reduction in symptoms compared with TAU. This study has led to a larger
      Stanley Medical Research Institute (SMRI)-funded, double-blind, randomized
      control trial.

PMID- 25057344
TI  - Ivabradine, a novel treatment for clozapine-induced sinus tachycardia: a case
      series.
AB  - OBJECTIVES: Clozapine is the most efficacious treatment for treatment-resistant
      schizophrenia; however its use can be limited by intolerability. Sinus
      tachycardia is a common adverse event associated with clozapine use, which may
      lead to the premature discontinuation of clozapine. Traditionally, beta blockers
      are used to treat clozapine-associated tachycardia, though problems with
      intolerability and ineffectiveness can limit their utility. METHODS: In this
      article, we present two cases of patients with treatment-resistant schizophrenia
      who developed symptomatic tachycardia associated with clozapine therapy. RESULTS:
      We demonstrate that the novel heart rate controlling agent ivabradine can be
      effectively and safely used to control the heart rate and to allow for continued
      treatment with clozapine. CONCLUSION: This is the first report in the literature
      demonstrating that ivabradine appears to be a well tolerated agent, which should
      be considered as a symptomatic treatment of clozapine-induced tachycardia if the
      use of a beta blocker fails due to a lack of response or intolerability.

PMID- 25057345
TI  - Comparison of lithium, aripiprazole and olanzapine as augmentation to paroxetine
      for inpatients with major depressive disorder.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are considered first
      line treatments for major depressive disorders (MDD). It has been reported,
      however, that 30-40% of patients with MDD who received SSRIs failed to respond to
      treatment. Use of lithium (Li) to augment SSRIs seems to be the most common
      strategy in such cases. It was recently demonstrated that atypical antipsychotics
      are effective augmentation agents in MDD. Here, we present a randomized
      controlled study that compared augmentation with Li, olanzapine (OLA) or
      aripiprazole (ARI) in paroxetine-refractory patients with MDD. METHODS:
      Participants were 30 patients who met Diagnostic and Statistical Manual of Mental
      Disorders IV criteria for MDD and refractory to paroxetine treatment. Treatment
      with Li, OLA or ARI was added to paroxetine in a randomized protocol for 4 weeks.
      We defined the patients whose scores on the Hamilton Rating Scale for Depression
      decreased 50% or more as responders. RESULTS: Two patients dropped out because of
      adverse effects. Response rates to Li, OLA or ARI augmentation were 4/10 (40%),
      3/10 (30%) and 4/10 (40%), respectively. In addition, Li, OLA and ARI did not
      influence plasma paroxetine concentrations. CONCLUSIONS: We concluded that OLA or
      ARI could be used as alternatives to Li as options for patients who do not
      respond to paroxetine treatment.

PMID- 25057346
TI  - Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case
      reports.
AB  - Recently, both the manufacturer of quetiapine and the US Food and Drug
      Administration warned healthcare providers and patients about quetiapine-induced
      QTc interval prolongation and torsade de pointes (TdP) when using this drug
      within the approved labeling.  We reviewed the case-report literature and found
      12 case reports of QTc interval prolongation in the setting of quetiapine
      administration. There were no cases of quetiapine-induced TdP or sudden cardiac
      death (SCD) among patients using quetiapine appropriately and free of additional
      risk factors for QTc interval prolongation and TdP. Among the 12 case reports
      risk factors included female sex (nine cases), coadministration of a drug
      associated with QTc interval prolongation (eight cases), hypokalemia or
      hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems
      (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases).
      There were four cases of TdP. As drug-induced TdP is a rare event, prospective
      studies to evaluate the risk factors associated with QTc prolongation and TdP are
      difficult to design, would be very costly, and would require very large samples
      to capture TdP rather than its surrogate markers. Furthermore, conventional
      statistical methods may not apply to studies of TdP, which is rare and an
      'outlier' manifestation of QTc prolongation. We urge drug manufacturers and
      regulatory agencies to periodically publish full case reports of psychotropic
      drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and
      investigators may better understand the clinical implications of prescribing such
      drugs as quetiapine. 

PMID- 25057347
TI  - A living light bulb, ultrasensitive biodetection made easy.
AB  - A team of scientists led by Professor DW Pang at Wuhan University have developed
      a new class of fluorescence probes based on bacterial cells. These microbial
      factories manufacture semiconductor nanocrystals inside and display protein A
      molecules on cell surface, transforming Staphylococcus aureus (S. aureus) cells
      into highly fluorescent cellular beacons that can be easily adapted for detection
      of diverse biological targets. 

PMID- 25057350
TI  - Excessive occupational heat exposure: a significant ergonomic challenge and
      health risk for current and future workers.
AB  - Occupational heat exposure threatens the health of a worker not only when heat
      illness occurs but also when a worker's performance and work capacity is
      impaired. Occupational contexts that involve hot and humid climatic conditions,
      heavy physical workloads and/or protective clothing create a strenuous and
      potentially dangerous thermal load for a worker. There are recognized heat
      prevention strategies and international thermal ergonomic standards to protect
      the worker. However, such standards have been developed largely in temperate
      western settings, and their validity and relevance is questionable for some
      geographical, cultural and socioeconomic contexts where the risk of excessive
      heat exposure can be high. There is evidence from low- and middle-income tropical
      countries that excessive heat exposure remains a significant issue for
      occupational health. Workers in these countries are likely to be at high risk of
      excessive heat exposure as they are densely populated, have large informal work
      sectors and are expected to experience substantial increases in temperature due
      to global climate change. The aim of this paper is to discuss current and future
      ergonomic risks associated with working in the heat as well as potential methods
      for maintaining the health and productivity of workers, particularly those most
      vulnerable to excessive heat exposure. 

PMID- 25057351
TI  - Carriage of Staphylococcus aureus in Thika Level 5 Hospital, Kenya: a cross
      sectional study.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important
      nosocomial pathogen but little is known about its circulation in hospitals in
      developing countries. We aimed to describe carriage of S.aureus amongst
      inpatients in a mid-sized Kenyan government hospital. METHODS: We determined the
      frequency of S.aureus and MRSA carriage amongst inpatients in Thika Hospital,
      Kenya by means of repeated cross-sectional ward surveys. For all S.aureus
      isolates, we performed antibiotic susceptibility tests, genomic profiling using a
      DNA microarray and spa typing and MLST. RESULTS: In this typical mid-sized Kenyan
      Government hospital, we performed 950 screens for current carriage of S.aureus
      amongst inpatients over a four month period. We detected S.aureus carriage
      (either MSSA or MRSA) in 8.9% (85/950; 95%CI 7.1-10.8) of inpatient screens, but
      patients with multiple screens were more likely have detection of carriage. MRSA
      carriage was rare amongst S.aureus strains carried by hospital inpatients - only
      7.0% (6/86; 95%CI 1.5-12.5%) of all isolates were MRSA. Most MRSA (5/6) were
      obtained from burns patients with prolonged admissions, who only represented a
      small proportion of the inpatient population. All MRSA strains were of the same
      clone (MLST ST239; spa type t037) with concurrent resistance to multiple
      antibiotic classes. MSSA isolates were diverse and rarely expressed antibiotic
      resistance except against benzyl-penicillin and co-trimoxazole. CONCLUSIONS:
      Although carriage rates for S.aureus and the MRSA prevalence in this Kenyan
      hospital were both low, burns patient were identified as a high risk group for
      carriage. The high frequency of genetically indistinguishable isolates suggests
      that there was local transmission of both MRSA and MSSA.

PMID- 25057352
TI  - Mammary stem cells: expansion and animal productivity.
AB  - Identification and characterization of mammary stem cells and progenitor cells
      from dairy animals is important in the understanding of mammogenesis, tissue
      turnover, lactation persistency and regenerative therapy. It has been realized by
      many investigators that altered lactation, long dry periods (non-milking period
      between two consecutive lactation cycles), abrupt cessation of lactation (common
      in water buffaloes) and disease conditions like mastitis, greatly reduce milk
      yield thus render huge financial losses within the dairy sector. Cellular
      manipulation of specialized cell types within the mammary gland, called mammary
      stem cells (MaSCs)/progenitor cells, might provide potential solutions to these
      problems and may improve milk production. In addition, MaSCs/progenitor cells
      could be used in regenerative therapy against tissue damage caused by mastitis.
      This review discusses methods of MaSC/progenitor cell manipulation and their
      mechanisms in bovine and caprine animals. Author believes that intervention of
      MaSCs/progenitor cells could lessen the huge financial losses to the dairy
      industry globally. 

PMID- 25057359
TI  - The clinical and integrated management of COPD. An official document of AIMAR
      (Interdisciplinary Association for Research in Lung Disease), AIPO (Italian
      Association of Hospital Pulmonologists), SIMER (Italian Society of Respiratory
      Medicine), SIMG (Italian Society of General Medicine).
AB  - COPD is a chronic pathological condition of the respiratory system characterized
      by persistent and partially reversible airflow obstruction, to which variably
      contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway
      disease) and lung parenchyma (pulmonary emphysema). COPD can cause important
      systemic effects and be associated with complications and comorbidities. The
      diagnosis of COPD is based on the presence of respiratory symptoms and/or a
      history of exposure to risk factors, and the demonstration of airflow obstruction
      by spirometry. GARD of WHO has defined COPD "a preventable and treatable
      disease". The integration among general practitioner, chest physician as well as
      other specialists, whenever required, assures the best management of the COPD
      person, when specific targets to be achieved are well defined in a diagnostic and
      therapeutic route, previously designed and shared with appropriateness. The first
      line pharmacologic treatment of COPD is represented by inhaled long-acting
      bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60%
      predicted and >= 2 exacerbations/year, ICS may be added to LABA. The use of fixed
      dose, single-inhaler combination may improve the adherence to treatment. Long
      term oxygen therapy (LTOT) is indicated in stable patients, at rest while
      receiving the best possible treatment, and exhibiting a PaO2 <= 55 mmHg (SO2 <
      88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary
      arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit >
      55%. Respiratory rehabilitation is addressed to patients with chronic respiratory
      disease in all stages of severity who report symptoms and limitation of their
      daily activity. It must be integrated in an individual patient tailored treatment
      as it improves dyspnea, exercise performance, and quality of life. Acute
      exacerbation of COPD is a sudden worsening of usual symptoms in a person with
      COPD, over and beyond normal daily variability that requires treatment
      modification. The pharmacologic therapy can be applied at home and includes the
      administration of drugs used during the stable phase by increasing the dose or
      modifying the route, and adding, whenever required, drugs as antibiotics or
      systemic corticosteroids. In case of patients who because of COPD severity and/or
      of exacerbations do not respond promptly to treatment at home hospital admission
      should be considered. Patients with "severe" or "very severe" COPD who experience
      exacerbations should be carried out in respiratory unit, based on the severity of
      acute respiratory failure. An integrated system is required in the community in
      order to ensure adequate treatments also outside acute care hospital settings and
      rehabilitation centers. This article is being simultaneously published in
      Sarcoidosis Vasc Diffuse Lung Dis 2014, 31(Suppl. 1);3-21. 

PMID- 25057353
TI  - Defects in mitochondrial metabolism and cancer.
AB  - Cancer is a heterogeneous set of diseases characterized by different molecular
      and cellular features. Over the past decades, researchers have attempted to grasp
      the complexity of cancer by mapping the genetic aberrations associated with it.
      In these efforts, the contribution of mitochondria to the pathogenesis of cancer
      has tended to be neglected. However, more recently, a growing body of evidence
      suggests that mitochondria play a key role in cancer. In fact, dysfunctional
      mitochondria not only contribute to the metabolic reprogramming of cancer cells
      but they also modulate a plethora of cellular processes involved in
      tumorigenesis. In this review, we describe the link between mutations to
      mitochondrial enzymes and tumor formation. We also discuss the hypothesis that
      mutations to mitochondrial and nuclear DNA could cooperate to promote the
      survival of cancer cells in an evolving metabolic landscape. 

PMID- 25057360
TI  - On the ethics of withholding and withdrawing medical treatment.
AB  - A general rationale is presented for withholding and withdrawing medical
      treatment in end-of-life situations, and an argument is offered for the moral
      irrelevance of the distinction, both in the context of pharmaceutical treatments,
      such as chemotherapy in cancer, and in the context of life-sustaining treatments,
      such as the artificial ventilator in lateral amyotrophic sclerosis. It is argued
      that this practice is not equivalent to sanctioning voluntary active euthanasia
      and that it is not likely to favour it. 

PMID- 25057361
TI  - Turning the tide: a history and review of hyperhidrosis treatment.
AB  - Hyperhidrosis is a potential cause of severe physical and psychological distress,
      interfering in activities of daily living. Over the past 100 years, advances have
      been made regarding the treatment of this debilitating condition with some
      success. Surgical treatment with sympathectomy was successfully performed for
      hyperhidrosis in the early part of the 20th century, with various modifications
      of the technique over the past 100 years. Topical aluminium salt antiperspirants,
      anticholinergic medications, iontophoresis and botulinum toxin introduced less
      invasive ways to manage this condition. This historical review will enable
      dermatologists and non-dermatologists to manage this distressing condition. 

PMID- 25057362
TI  - Strategies to secure surgical research funding: fellowships and grants.
AB  - Innovation and advances in surgery are entirely dependent on research.
      Fellowships and grants are the principal means by which surgical research
      projects are funded. However, these are scarce and highly competitive. This
      article offers guidance through the application process for the aspiring academic
      surgeon. Approaching the application in a timely and structured manner, seeking
      advice from current and previous award-holders and members of review panels, and
      obtaining preliminary data are key ingredients to success. 

PMID- 25057363
TI  - A randomised controlled trial of topical Kanuka honey for the treatment of
      eczema.

PMID- 25057364
TI  - Vaccine-derived poliomyelitis and postpolio syndrome: an Italian Cutter Incident.
AB  - Post-polio syndrome is a condition characterized by increased muscle weakness,
      atrophy, fatigue and pain developing several years after the acute polio event.
      We describe a 52-year-old patient who experienced post-polio syndrome; he had
      contracted acute paralytic poliomyelitis at 12 months of age, shortly after the
      third dose of Salk polio vaccine. 

PMID- 25057365
TI  - Eligibility for bariatric surgery among adults in England: analysis of a national
      cross-sectional survey.
AB  - OBJECTIVES: This study aimed to determine the number eligible for bariatric
      surgery and their sociodemographic characteristics. DESIGN: We used Health Survey
      for England 2006 data, representative of the non-institutionalized English
      population. SETTING: The number of people eligible for bariatric surgery in
      England based on national guidance is unknown. The UK National Institute for
      Health and Clinical Excellence criteria for eligibility are those with body mass
      index (BMI) 35-40 kg/m(2) with at least one comorbidity potentially improved by
      losing weight or a BMI > 40 kg/m(2). PARTICIPANTS: Of 13,742 adult respondents
      (>=18 years), we excluded participants with invalid BMI (n = 2103), comorbidities
      (n = 2187) or sociodemographic variables (n = 27) data, for a final study sample
      of 9425 participants. MAIN OUTCOME MEASURES: The comorbidities examined were
      hypertension, type 2 diabetes, stroke, coronary heart disease and osteoarthritis.
      Sociodemographic variables assessed included age, sex, employment status, highest
      educational qualification, social class and smoking status. RESULTS: 5.4% (95% CI
      5.0-5.9) of the non-institutionalized adult population in England could meet
      criteria for having bariatric surgery after accounting for survey weights. Those
      eligible were more likely than the general population to be women (60.1% vs.
      39.9%, p<0.01), retired (22.4% vs. 12.8% p<0.01), and have no formal educational
      qualifications (35.7% vs. 21.3%, p<0.01). CONCLUSIONS: The number of adults
      potentially eligible for bariatric surgery in England (2,147,683 people based on
      these results and 2006 population estimates) far exceeds previous estimates of
      eligibility. In view of the sociodemographic characteristics of this group,
      careful resource allocation is required to ensure equitable access on the basis
      of need.

PMID- 25057366
TI  - A critical review of the core medical training curriculum in the UK: A medical
      education perspective.
AB  - This paper represents a systematic evaluation of the Core Medical Training
      Curriculum in the UK. The authors critically review the curriculum from a medical
      education perspective based mainly on the medical education literature as well as
      their personal experience of this curriculum. They conclude in practical
      recommendations and suggestions which, if adopted, could improve the design and
      implementation of this postgraduate curriculum. The systematic evaluation
      approach described in this paper is transferable to the evaluation of other
      undergraduate or postgraduate curricula, and could be a helpful guide for medical
      teachers involved in the delivery and evaluation of any medical curriculum. 

PMID- 25057367
TI  - Multimorbidity and unmet citizens' needs and expectations urge for reforms in the
      health system of Cyprus: a questionnaire survey.
AB  - OBJECTIVE: This study aims to investigate the prevalence of multimorbidity in
      Cyprus and the extent to which citizens are satisfied with the currently provided
      healthcare and to provide recommendations on the basis of findings. DESIGN: A
      nationally based survey conducted through personal interviews, using a structured
      questionnaire designed for this survey. SETTING: Cyprus rural and urban areas
      (excluding Turkish occupied areas). PARTICIPANTS: Four hundred and sixty-five
      Cypriot adults, average age 53 years. MAIN OUTCOME MEASURES: Lifetime prevalence
      of self-reported non-communicable diseases. RESULTS: This study demonstrated
      initial evidence for a high prevalence of non-age specific multimorbidity among
      Cypriots and dissatisfaction with their doctors, especially for the time
      allocated to discuss their general state of health. Recommendations focus on a
      new cost-effective, person-centred model of healthcare. The model prioritizes
      prevention rather than treatment, targeting the determinants of complexity before
      their influences create conditions that demand high-cost interventions, and it is
      based on three fundamental principles: (1) tackling health as a political issue,
      (2) empowering the patient and (3) introducing Applied Nutrition in the system.
      CONCLUSIONS: This study threw light into the issue of patient complexity and
      revealed unmet people's needs and expectations for a more person-centred care,
      providing a first challenge to the single disease-based system of healthcare in
      Cyprus. The findings of the study may have important implications for government
      policies and highlight the need for more research in this area to inform policy
      makers, particularly in view of the fact that a new Health System is currently
      being designed.

PMID- 25057368
TI  - Medical student syndrome: fact or fiction? A cross-sectional study.
AB  - OBJECTIVES: It is often reported by medical practitioners that medical students
      develop hypochondriacal concerns and symptoms relating to diseases they are
      studying, a phenomenon labelled 'medical student syndrome'. However, the evidence
      that this syndrome exists and particularly that it contributes to an increased
      number of consultations (as typical hypochondriasis does) is weak. The present
      study investigates this phenomenon in terms of differences between medical and
      non-medical students in help-seeking behaviour. DESIGN: Cross-sectional survey.
      SETTING: Three universities in London. PARTICIPANTS: Medical students (n = 103),
      non-medical science student controls (n = 107) and law student controls (n = 78),
      all third-year undergraduates, were recruited from within their universities.
      MAIN OUTCOME MEASURES: Help-seeking behaviour was measured using the 'Health
      Anxiety Questionnaire' reassurance-seeking behaviour subscale; the overall number
      of doctors' visits made for new health complaints since beginning university; a
      new 'Hypochondriacal and Help-Seeking Behaviour' scoring-system, which asked
      questions pertaining to not just the number but the nature of consultations,
      identifying participants who had experienced health concerns that were
      disproportionate to the diseases diagnosed. RESULTS: No significant differences
      were found between medical students and either control group in any of the main
      outcome variables. CONCLUSIONS: These findings fail to support the notion that
      medical students, more so than other students, seek medical advice for
      hypochondriacal health concerns. They are pertinent to clinicians due to the
      potentially negative consequences of incorrectly assuming medical students to
      behave in this way, including cursory evaluations and disintegration of the
      doctor-patient relationship.

PMID- 25057369
TI  - Improving medication safety in UK care homes: challenges and current perspective.
AB  - In the UK, there are policy and regulatory concerns regarding the governance of
      care homes and healthcare provision within these homes. From a public health
      perspective, these issues can pose significant challenges to the provision of
      safe and quality medication use services to care home residents. The objective of
      this paper is to highlight an important and neglected issue for the growing
      population of institutionalized older adults. We reviewed relevant literature for
      the years 2000 to present and identified recent efforts undertaken to improve
      medication safety standards in UK care homes. We consider the limitations and
      reasons for the National Health Service's restricted role and lack of leadership
      in providing medical services for this institutionalized population. The efforts
      taken by the Department of Health and other healthcare authorities targeting
      medication safety in care homes are also highlighted. In order to improve the
      quality of healthcare, specifically in areas related to medication safety and
      quality use of medicines, interventions need to be taken by the national
      government and similarly by local authorities and NHS commissioners. 

PMID- 25057370
TI  - A retrospective review of the assessment of current perioperative management of
      diabetes in patients undergoing knee replacement surgery.
AB  - OBJECTIVES: The prevalence of diabetes mellitus is increasing. Previous work has
      shown that suboptimal glycaemic control is associated with poor perioperative
      outcomes with increased rates of postoperative morbidity and mortality in several
      surgical specialities. Recently published UK guidelines have laid out the
      standards of perioperative care for patients with diabetes. Because an increasing
      number of patients with diabetes undergo surgery, it is important that these
      nationally agreed standards of care are adhered to. DESIGN: A retrospective
      review of the standard of care of patients against existing audit standards laid
      down in national guidelines, and a comparison of outcomes with people without
      diabetes. SETTING: A single major orthopaedic department. PARTICIPANTS: Fifty
      consecutive patients undergoing knee arthroplasty between July 2010 and June
      2011. MAIN OUTCOME MEASURES: Postoperative complications; pre, peri and
      postoperative glucose control; hospital length of stay. RESULTS: Although there
      were no serious postoperative complications, the pre, peri and postoperative
      management was found to be suboptimal, particularly with reference to
      optimization of blood glucose control, both in terms of HbA1c preoperatively and
      blood glucose monitoring perioperatively. The average length of hospital stay was
      not different between groups; however, 36 patients with diabetes had at least one
      documented hyperglycaemic episode and four at least one hypoglycaemic episode.
      CONCLUSIONS: Perioperative care of diabetes in patients undergoing knee
      arthroplasty could be improved. Several changes have been made since this audit
      was carried out, in particular adoption of the comprehensive Joint British
      Diabetes Societies Guideline on the perioperative management of adult patients
      with diabetes.

PMID- 25057371
TI  - A questionnaire-based survey investigating the current use of tranexamic acid in
      traumatic haemorrhage and elective hip and knee arthroplasty.
AB  - OBJECTIVES: To record the current use of tranexamic acid during traumatic
      haemorrhage and elective arthroplasty of the hip and knee. DESIGN: A
      questionnaire-based postal survey. SETTING: The questionnaire was sent to the
      'anaesthetic lead' at all acute trusts in England, excluding centres for
      children, women's health, cancer and cardiac care. PARTICIPANTS: Ninety-nine
      (66%) centres replied to the questionnaire. MAIN OUTCOME MEASURES: Is tranexamic
      acid used as part of routine standardized treatment for traumatic haemorrhage and
      for elective hip and knee arthroplasty, and if so what dosage regime was
      administered? RESULTS: Few trusts (31%) use tranexamic acid during traumatic
      haemorrhage, with various dosages used. Its use in hip and knee arthroplasty was
      also low (38%) with a diverse range of doses prescribed. CONCLUSIONS: Despite
      many trials showing its efficacy and low risk of side effect, it is clear that
      its use is not part of standard practice in most centres. Further studies could
      clarify these concerns and provide a definitive dosing schedule improving patient
      care and saving lives.

PMID- 25057372
TI  - Caloric and nutrient intake in children with attention deficit hyperactivity
      disorder treated with extended-release methylphenidate: analysis of a cross
      sectional nutrition survey.
AB  - OBJECTIVES: To study calorie and nutrients intake in a group of patients
      diagnosed with attention deficit hyperactivity disorder (ADHD) under treatment
      with extended-release methylphenidate (MPH-ER), and to analyse the need to design
      nutrition intervention strategies. DESIGN: Observational (case-control). SETTING:
      Navarra Hospital Complex, Pamplona, Spain. PARTICIPANTS: A total of 100 patients
      diagnosed with ADHD under treatment with MPH-ER and 100 healthy children (control
      group). MAIN OUTCOME MEASURES: A nutrition survey was carried out (food intake
      registration of 3 consecutive school days). Calorie and nutrient intake, as well
      as nutrition status, were evaluated and compared in both groups. RESULTS:
      Nutritional status in ADHD group was significantly lower (p < 0.05) than in
      control group. Calorie intake in mid-morning snack, lunch and afternoon snack was
      significantly higher (p < 0.05) in the control group. Calorie intake in supper
      was significantly higher (p < 0.05) in the ADHD group. There were no significant
      differences in breakfast. Total calorie intake, as well as protein,
      carbohydrates, fat, fibre, calcium, iron, magnesium, zinc, selenium and
      phosphorous, thiamine, niacin, vitamin B6 and folate intake, in control group was
      significantly higher than in ADHD group. CONCLUSIONS: The daily calorie and
      nutrients intake in patients under treatment with MPH-ER is, generally, lower
      than in healthy population of similar age. The need to impart programmes of
      nutrition education simultaneously with multimodal treatment in order to avoid
      the nutrition consequences of treatment with MPH should be considered.

PMID- 25057373
TI  - Evaluation of the first year of the Oxpal Medlink: A web-based partnership
      designed to address specific challenges facing medical education in the occupied
      Palestinian territories.
AB  - OBJECTIVES: To (1) evaluate educational needs of clinical students at Al-Quds
      University Medical School in the West Bank; (2) address these needs where
      possible using synchronous distance learning, with clinicians in Oxford providing
      case-based tutorials to undergraduates in the West Bank via an online platform
      (WizIQ) and (3) assess the impact of this education. DESIGN: Review of online
      OxPal Medlink database for tutorials held between March 2012 and April 2013.
      Needs assessment and evaluation of student and tutor experiences through online
      questionnaires, focus groups and semi-structured interviews. SETTING: Oxford
      University Hospitals, Oxford, UK, and Al-Quds University Medical School, Abu
      Dies, Palestine. PARTICIPANTS: Doctors at Oxford University Hospitals and fourth
      , fifth- and sixth-year medical students and faculty members at Al-Quds Medical
      School. MAIN OUTCOME MEASURES: Number of tutorials, student participation,
      student-rated satisfaction and qualitative feedback from tutors and students.
      RESULTS: Students demonstrated strong theoretical knowledge but struggled to
      apply this in presentation-based scenarios. Between March 2012 and April 2013, 90
      tutorials were delivered to 60 students. Feedback: >95% respondents rated
      tutorials as 'Excellent' or 'Good' and 'Very' or 'Fairly' relevant to their
      future practice in Palestine. Students reported the programme had modified their
      approach to patients but requested better synchronization with concurrent
      attachments and clarification of learning outcomes. CONCLUSIONS: OxPal Medlink is
      a novel, web-based distance-learning partnership designed to overcome some of the
      challenges to local medical education in the occupied Palestinian territories.
      Evaluation of the first year indicates teaching is relevant to local practice and
      of high quality. This approach may have the potential to strengthen local
      capacity for medical education.

PMID- 25057374
TI  - Wernicke-Korsakoff syndrome in a patient with self-neglect associated with severe
      depression.
AB  - Wernicke-Korsakoff syndrome is a neuropsychiatric disorder resulting from
      thiamine deficiency and commonly associated with chronic alcoholism, but we
      describe the first case report resulting from self-neglect associated with
      depression. 

PMID- 25057375
TI  - Work-based assessments: making the transition from participation to engagement.
AB  - Work-based assessments (WBAs) were only recently introduced into medicine.
      However, since their introduction, they have rapidly grown in popularity. WBAs
      are now a routine part of medical training. As WBAs are being implemented, the
      practical difficulties with their use have come to light. A major problem is
      failure of the trainees, trainers and training programmes to adequately engage
      with them. In this review, the reasons for this and how these can be overcome are
      discussed. 

PMID- 25057377
TI  - A randomised controlled trial of topical Kanuka honey for the treatment of
      psoriasis.

PMID- 25057376
TI  - Invasive candidiasis in intensive care unit; consensus statement from an Iranian
      panel of experts, July 2013.
AB  - Invasive candidiasis (IC) is associated with high mortality in intensive care
      unit (ICU) patients. Timely diagnosis of this potentially fatal condition remains
      a challenge; on the other hand, the criteria for initiating empirical antifungal
      therapy in critically ill patients are not well defined in different patient
      population and ICU settings. Alongside the international guidelines, reaching
      regional and local consensus on diagnosis and management of IC in ICU setting is
      essential. This report summarizes our present status of IC management in ICU,
      considered by a group of Iranian experts in the fields of intensive care and
      infectious diseases. A round table of 17 experts was held to review the available
      data and discuss the optimal treatment strategies for IC in critical care
      setting. Comparative published data on the management of IC were analytically
      reviewed and the commonly asked questions about the management of IC in ICU were
      isolated. These questions were interactively discussed by the panel and audience
      responses were taken to consolidate point-to-point agreement with the panel
      arriving at consensus in many instances. The responses indicated that patients'
      risk stratification, clinical discretion, fungal diagnostic techniques and the
      empirical therapy for IC are likely to save more patients. Treatment options were
      recommended to be based on the disease severity, prior azole exposure, and the
      presence of suspected azole-resistant Candida species. This report was reviewed,
      edited and discussed by all participants to include further evidence-based
      insights. The panel expects such endorsed recommendations to be soon formulated
      for implementation across the country. 

PMID- 25057378
TI  - A nationwide analysis of successful litigation claims in neurological practice.
AB  - OBJECTIVES: Neurological practice has previously been highlighted as a high-risk
      speciality with regard to malpractice claims. We set out to study the nature of
      these claims in order to inform physicians about hazardous areas within their
      speciality and potentially alter clinical practice. DESIGN: Nationwide
      retrospective analysis of successful neurology and neurosurgery claims over a 17
      year period. SETTING: We studied all successful claims occurring between 1995 and
      2012 using the NHS Litigation Authority database, which collects data on claims
      made against clinicians practising in England and Wales. PARTICIPANTS: Four
      hundred and twenty-three successful claims were identified during the study
      period. MAIN OUTCOME MEASURES: The errors involved, the patient groups affected,
      the resulting mortality and the litigation payments. RESULTS: 63.1% of claims
      were due to negligence in neurosurgical care, whilst 36.9% were due to negligence
      in neurological care. Litigation payments were significantly higher in
      neurosurgery compared to neurology cases. Diagnostic error was the most common
      cause of litigation. The disease categories with the highest numbers of
      successful litigation claims were spinal pathology, cerebrovascular disease
      including subarachnoid haemorrhage, intracranial tumours, hydrocephalus and
      neuropathy/neuromuscular disease. CONCLUSIONS: This is the first study of
      successful litigation claims against the NHS for negligent neurological or
      neurosurgical care and provides data to help reduce risk and improve patient
      safety.

PMID- 25057379
TI  - Noncardiac chest pain in a patient with cardiac pathology: the importance of an
      accurate history.

PMID- 25057380
TI  - Updating the evidence for the effect of radiofrequency catheter ablation on left
      atrial volume and function in patients with atrial fibrillation: a meta-analysis.
AB  - OBJECTIVES: To systematically review the effects of radiofrequency catheter
      ablation (RFCA) on left atrial (LA) size, volumes and function in patients with
      atrial fibrillation (AF). METHODS: We searched MEDLINE, EMBASE, ScienceDirect,
      Highwire, Cochrane Central Register of Controlled Trials, Cochrane Database of
      Systematic Reviews and the reference lists of retrieved reports in July 2012.
      SETTING: China. PARTICIPANTS: Twenty-six studies (enrolling 1821 patients) were
      included in the final analysis. MAIN OUTCOME MEASURES: Changes of LA size or
      volumes and/or function in patients with AF after RFCA. RESULTS: Compared to pre
      ablation values, there were significant decreases in LA diameter and LA volumes
      at post-ablation follow-up. However, compared to pre-ablation values, there were
      no significant differences in LA ejection fraction/LA active emptying fraction
      and LA strain at post-ablation follow-up. Decreases in LA diameter and LA volumes
      remained significant in those without AF recurrence but not in those with AF
      recurrence. LA ejection fraction/LA active emptying fraction did not decrease in
      patients without AF recurrence, whereas they decreased in patients with AF
      recurrence. As for LA strain, it seems that LA strain increases in patients
      without AF recurrence, with less fibrosis and with more LA volumes decrease, but
      the differences were not significant. CONCLUSIONS: Successful RFCA in patients
      with AF significantly decreases LA size and volumes and does not seem to
      adversely affect LA function.

PMID- 25057381
TI  - Listeria meningitis and resultant symptomatic hydrocephalus complicating
      infliximab treatment for ulcerative colitis.
AB  - Listeria monocytogenes, an uncommon pathogen, should be considered by clinicians
      as a source of sepsis and meningitis in the immunocompromised individuals,
      including those on anti-TNF alpha agents. Immunosuppressant agents including
      biologic therapies have transformed the management of various rheumatological and
      dermatological conditions.(1) We report a case of life-threatening L.
      monocytogenes sepsis and meningitis in a 75-year-old man receiving infliximab for
      severe ulcerative colitis (UC). 

PMID- 25057383
TI  - Studying medicine - a cross-sectional questionnaire-based analysis of the
      motivational factors which influence graduate and undergraduate entrants in
      Ireland.
AB  - OBJECTIVES: The number of places available in Ireland for graduate entry to
      medical school has steadily increased since 2006. Few studies have, however,
      characterized the motivational factors underlying decision to study medicine via
      this route. We compared the factors motivating graduate entrants versus
      undergraduate entry (UGE) students to choose medicine as a course of study.
      DESIGN: The present study was a quantitative cross-sectional questionnaire-based
      investigation. SETTING: The study was conducted in University College Cork and
      University of Limerick, Ireland. PARTICIPANTS: It involved 185 graduate entry
      (GE) and 120 UGE students. OUTCOME MEASURES: QUESTIONNAIRES WERE DISTRIBUTED TO
      STUDENTS ADDRESSING THE FOLLOWING AREAS: demographic/academic characteristics;
      factors influencing the selection of academic institution and motivation to study
      medicine; and the role of career guidance in choice of study. RESULTS: When asked
      to list reasons for selecting medicine, both groups listed a wish to help and
      work with people, and a desire to prevent and cure disease. UGE students were
      significantly more motivated by intellectual satisfaction, encouragement by
      family/friends, financial reasons, and professional independence. Approximately
      half of GE students selected their first degree with a view to potentially
      studying medicine in the future. GE and UGE students differed significantly with
      respect to sources consulted for career guidance and source of study information.
      CONCLUSIONS: This study is the first systematic examination of study and career
      motivation in GE medical students since the programme was offered by Irish
      universities and provides insight into the reasons why graduate entrants in
      Ireland choose to study medicine via this route.

PMID- 25057384
TI  - An investigation into the prevalence of paratracheal air cysts revealed on
      multidetector computed tomography.

PMID- 25057385
TI  - Novel low density lipoprotein receptor variant linked to early onset acute
      myocardial infarction in a patient with familial hypercholesterolaemia.
AB  - A novel LDL-receptor gene variant was found responsible for previously undetected
      familial hypercholesterolaemia and acute myocardial infarction in a young man. 

PMID- 25057386
TI  - A short clinical review of vaccination against measles.
AB  - Major epidemics of measles are again in the news across the UK because of our
      failure to maintain population herd immunity. This situation has occurred
      primarily because of a loss of public confidence in the measles, mumps and
      rubella (MMR) vaccine, which was never restored following the Wakefield debacle,
      and a lack of awareness of the potential morbidity and mortality associated with
      measles. This article provides healthcare professionals with a succinct overview
      of important clinical aspects of measles and also describes the history of
      measles vaccination in the UK. Restoration of herd immunity will require higher
      public acceptance of the MMR vaccine in the context of recognition that measles
      remains an important infection. While achievement of this appears to be
      challenging, recent UK-based research suggests that it can be ascertained. 

PMID- 25057387
TI  - The history of the case report: a selective review.
AB  - The clinical case report is a popular genre in medical writing. While authors and
      editors have debated the justification for the clinical case report, few have
      attempted to examine the long history of this genre in medical literature. By
      reviewing selected literature and presenting and discussing excerpts of clinical
      case reports from Egyptian antiquity to the 20th century, we illustrate the
      presence of the genre in medical science and how its form developed. Central
      features of the clinical case report in different time periods are discussed,
      including its main components, structure, style and author presence. 

PMID- 25057388
TI  - Meningiomas occurring during long-term survival after treatment for childhood
      cancer.
AB  - Childhood cancer is rare but improvements in treatment over the past five decades
      have resulted in a cohort of more than 30,000 long-term survivors of childhood
      cancer in the UK with more added annually. These long-term survivors are at risk
      of late effects of cancer treatment which replace original tumour recurrence as
      the leading cause of premature death. Second neoplasms are a particular risk and
      in the central nervous system meningiomas occur increasingly with increased
      radiation dose to central nervous system tissue and length of time after
      exposure, resulting in a 500-fold increase above that expected in the normal
      population by 40 years of follow up. This multidisciplinary author group and
      others met to discuss the issue. Our pooled information, and consensus that
      screening should only follow symptoms, was published online by the Royal College
      of Radiologists in 2013. We outline here the current knowledge and management of
      these neoplasms secondary to childhood cancer treatment. 

PMID- 25057389
TI  - Magnetic resonance imaging of the cardiac manifestations of Churg-Strauss.
AB  - Through the detection of acute inflammation, edema, and fibrosis, cardiac
      magnetic resonance imaging provides a complete and safe evaluation of the
      myocardium in Churg-Strauss disease and is a useful tool for following the
      disease course. 

PMID- 25057390
TI  - A retrospective study of cognitive function in doctors and dentists with
      suspected performance problems: an unsuspected but significant concern.
AB  - OBJECTIVE: To examine the performance assessments and cognitive function of
      practitioners referred to the National Clinical Assessment Service (NCAS).
      DESIGN: Retrospective observational study. SETTING: Practitioners referred to
      NCAS for performance assessment due to suspected performance problems.
      PARTICIPANTS: One hundred and nine practitioners over the age of 45 years
      referred to NCAS between 1 September 2008 and 30 June 2012. MAIN OUTCOME
      MEASURES: Reasons for referral of practitioners and their characteristics;
      details of their assessments including screening for cognition using
      Addenbrooke's Cognitive Examination Revised (ACE-R); outcome of the process.
      RESULTS: Reasons for referral included 'clinical difficulties' and 'governance or
      safety issues'. Eighty-seven practitioners scored above 88 on ACE-R. Twenty-two
      were found to have an ACE-R score of <=88. On further assessment, 14 of these 22
      practitioners were found to have cognitive impairment. The majority of all
      practitioners were found to be performing below the expected level of practice
      for someone at their grade and specialty. Of those scoring <=88 on the screening,
      only seven continued in clinical practice. CONCLUSIONS: A high proportion of
      practitioners scoring poorly on ACE-R were found to have cognitive impairment
      following detailed neuropsychological testing, the youngest aged 46 years. Many
      were working in isolation. Nearly all practitioners scoring poorly on ACE-R were
      international medical graduates; reasons for this are unclear. Performance
      assessment results showed persisting failings in the practitioners' record
      keeping and in their assessment of patients. Our findings highlight the need for
      increased vigilance and training of responsible officers to recognise performance
      problems and emphasise the importance of comprehensive assessment.

PMID- 25057391
TI  - Discrepancies between registration and publication of randomised controlled
      trials: an observational study.
AB  - OBJECTIVES: To determine the consistency between information contained in the
      registration and publication of randomised controlled trials (RCTs). DESIGN: An
      observational study of RCTs published between May 2011 and May 2012 in the
      British Medical Journal (BMJ) and the Journal of the American Medical Association
      (JAMA) comparing registry data with publication data. PARTICIPANTS AND SETTINGS:
      Data extracted from published RCTs in BMJ and JAMA. MAIN OUTCOME MEASURES: Timing
      of trial registration in relation to completion of trial data collection and
      publication. Registered versus published primary and secondary outcomes, sample
      size. RESULTS: We identified 40 RCTs in BMJ and 36 in JAMA. All 36 JAMA trials
      and 39 (98%) BMJ trials were registered. All registered trials were registered
      prior to publication. Thirty-two (82%) BMJ trials recorded the date of data
      completion; of these, in two trials the date of trial registration postdated the
      registered date of data completion. There were discrepancies between primary
      outcomes declared in the trial registry information and in the published paper in
      18 (47%) BMJ papers and seven (19%) JAMA papers. The original sample size stated
      in the trial registration was achieved in 24 (60%) BMJ papers and 21 (58%) JAMA
      papers. CONCLUSIONS: Compulsory registration of RCTs is meaningless if the
      content of registry information is not complete or if discrepancies between
      registration and publication are not reported. This study demonstrates that
      discrepancies in primary and secondary outcomes and sample size between trial
      registration and publication remain commonplace, giving further strength to the
      World Health Organisation's argument for mandatory completion of a minimum number
      of compulsory fields.

PMID- 25057392
TI  - Systematic review of new medics' clinical task experience by country.
AB  - OBJECTIVES: There is a need for research which informs on the overall size and
      significance of clinical skills deficits among new medics, globally. There is
      also the need for a meta-review of the similarities and differences between
      countries in the clinical skills deficits of new medics. DESIGN: A systematic
      review of published literature produced 68 articles from Google/Google Scholar,
      of which nine met the inclusion criteria (quantitative clinical skills data about
      new medical doctors). PARTICIPANTS: One thousand three hundred twenty-nine new
      medical doctors (e.g. foundation year-1s, interns, postgraduate year-1 doctors).
      SETTING: Ten countries/regions. MAIN OUTCOME MEASURES: One hundred twenty-three
      data points and representation of a broad range of clinical procedures. RESULTS:
      The average rate of inexperience with a wide range of clinical procedures was
      35.92% (lower confidence interval [CI] 30.84, upper CI 40.99). The preliminary
      meta-analysis showed that the overall deficit in experience is significantly
      different from 0 in all countries. Focusing on a smaller selection of clinical
      skills such as catheterisation, IV cannulation, nasogastric tubing and
      venepuncture, the average rate of inexperience was 26.75% (lower CI 18.55, upper
      CI 35.54) and also significant. England presented the lowest average deficit
      (9.15%), followed by New Zealand (18.33%), then South Africa (19.53%), Egypt,
      Kuwait, Gulf Cooperation Council countries and Ireland (21.07%), after which was
      Nigeria (37.99%), then USA (38.5%) and Iran (44.75%). CONCLUSION: A meta-analysis
      is needed to include data not yet in the public domain from more countries. These
      results provide some support for the UK General Medical Council's clear, detailed
      curriculum, which has been heralded by other countries as good practice.

PMID- 25057393
TI  - Oral gel choline salicylate induced refractory gastric ulceration.
AB  - Common over the counter oral ulcer soothing gel can be an unexpected source of
      salicylate and cause refractory gastrointestinal ulcers if not identified. 

PMID- 25057394
TI  - Successful low-dose thrombolysis of submassive pulmonary embolus in a pregnant
      patient.
AB  - Low-dose thrombolysis was effective and safe in a pregnant woman with acute
      pulmonary embolism causing severe right ventricular dysfunction. This is the
      first reported case of successful thrombolysis for pulmonary embolus in pregnancy
      in the absence of shock. 

PMID- 25057395
TI  - Invasive medical procedure skills amongst Foundation Year Doctors - a
      questionnaire study.
AB  - OBJECTIVES: Competency in practical skills is an important aspect of training for
      medical doctors. This questionnaire survey aimed to investigate if the current
      Foundation Year trainees have performed several practical procedures of
      importance and their level of confidence in carrying them out unsupervised.
      DESIGN: Questionnaire study. SETTING: Five National Health Service hospitals in
      England. PARTICIPANTS: A total of 103 Foundation Year trainees responded to the
      survey (73 FY1s; 30 FY2s). MAIN OUTCOME MEASURES: Percentage of trainees who have
      performed these skills and their average level of confidence. RESULTS: The
      percentage of trainees who have performed these skills and their average level of
      confidence (scale of 1 to 5) are as follows: intubation (32%, 1); chest drain
      (33%, 1); central line (26%, 1); femoral line (23%, 1); peripheral line (28%, 1);
      lumbar puncture (64%, 3); ascitic tap (57%, 3). Only 25% of the trainees have
      attended certified training courses on these skills during their Foundation Year
      training. More than half of these trainees (73%) found the courses very useful.
      Ninety-two per cent of trainees who did not attend practical skill courses are
      very interested to attend them. All the trainees agreed that these courses should
      be available for all the Foundation Year doctors, and 92% believe that these
      courses are most beneficial during the Foundation Year 1 training. CONCLUSION:
      Most Foundation Year trainees have low confidence and exposure to these important
      practical skills. Certified practical skills courses should be made available to
      the Foundation Year doctors for the benefit of their training. This will also
      increase the quality of patient care.

PMID- 25057396
TI  - An analysis of National Health Service Trust websites on the occupational
      backgrounds of 'Non-Executive Directors' on England's Acute Trusts.
AB  - OBJECTIVES: To explore the occupational backgrounds of English Non-Executive
      Directors (NED) on Acute National Health Service (NHS) Trusts. DESIGN: Data
      extrapolated from Trust websites of NED' occupational backgrounds by gender and
      occupations, and inter-rater reliability test undertaken. SETTING: Data were
      available on all but 24 of the 166 Acute Trusts' from all regions. PARTICIPANTS:
      Trust Chairs and NED were categorised by their dominant occupation. MAIN OUTCOME
      MEASURE: Differentiating NED with and without health or social care leadership
      experience. RESULTS: The ratings of NED' occupations positively correlated (p <
      0.001). Occupational categories were Commerce and Finance from private and public
      sectors or with Medical or Community leadership experience. Only 4% of Chairs
      were Medical, 2% from Community - the majority (61%) from Commerce and Finance.
      Of the 1001 NED, 8% and 6% respectively had Medical or Community leadership
      experience; most (86%) were Commerce, Finance and non-clinical Managerial
      backgrounds. Females made up 27% of NED. CONCLUSIONS: With a predominance of
      Chairs and NED without health or social care leadership experience, are current
      Boards equipped to avoid inadvertently 'doing the system's business' (Francis,
      2013) rather than developing a more patient-centred, clinically led and
      integrated NHS? It is suggested that Boards need more NED with health and social
      care leadership experience and methods to identify the 'patient's agenda' to
      create 'a common culture' that places 'patients at the centre of everything we
      do' (Hunt, 2012). A key context for Trust Boards operations is funding, which
      Francis' terms of reference excluded, an issue that is briefly discussed.

PMID- 25057397
TI  - Comparison of bias resulting from two methods of self-reporting height and
      weight: a validation study.
AB  - OBJECTIVES: To contrast the validity of two modes of self-reported height and
      weight data. DESIGN: Subjects' self-reported height and weight by mailed survey
      without expectation of subsequent measurement. Subjects were later offered a
      physical exam, where they self-reported their height and weight again, just prior
      to measurement. Regression equations to predict actual from self-reported body
      mass index (BMI) were fitted for both sets of self-reported values. Residual
      analyses assessed bias resulting from application of each regression equation to
      the alternative mode of self-report. Analyses were stratified by gender. SETTING:
      Upstate New York. PARTICIPANTS: Subjects (n = 260) with survey, pre-exam and
      measured BMI. MAIN OUTCOME MEASURES: Prevalence of obesity based on two modes of
      self-report and also measured values. Bias resulting from misapplication of
      correction equations. RESULTS: Accurate prediction of measured BMI was possible
      for both self-report modes for men (R (2 )= 0.89 survey, 0.85 pre-exam) and women
      (R (2 )= 0.92 survey, 0.97 pre-exam). Underreporting of BMI was greater for
      survey than pre-exam but only significantly so in women. Obesity prevalence was
      significantly underestimated by 10.9% (p < 0.001) and 14.9% (p < 0.001) for men
      and 5.4% (p = 0.007) and 11.2% (p < 0.001) for women, for pre-exam and survey,
      respectively. Residual analyses showed that significant bias results when a
      regression model derived from one mode of self-report is used to correct BMI
      values estimated from the alternative mode. CONCLUSIONS: Both modes significantly
      underestimated obesity prevalence. Underestimation of actual BMI is greater for
      survey than pre-exam self-report for both genders, indicating that equations
      adjusting for self-report bias must be matched to the self-report mode.

PMID- 25057398
TI  - Low-back pain, lassitude and loss of appetite.
AB  - White blood cells, Erythrocyte sedimentation rate and C-reactive protein are
      sensitive tools to discover rare, but potentially serious pyogenic vertebral
      osteomyelitis, a disease whose incidence is increasing. 

PMID- 25057399
TI  - Thoracic amyloidomas: Two case reports of an evasive diagnosis.
AB  - Amyloidosis is a rare differential diagnosis of a mass detected in the chest.
      Amyloidoma is caused by a local proliferation of clonal B-cells secreting an
      unstable immunoglobulin light chain which accumulates. FDG-PET scan are useful
      but not specific. Treatment is generally by local resection for treatment of
      symptoms. We report two cases of amyloidomas, which are rare entities
      characterised by large local amyloid deposits. These can occur in the upper
      respiratory tract, soft tissues and central nervous system.(1.) 

PMID- 25057400
TI  - Carotid sinus malfunction presenting with presyncopal episodes during radiation
      therapy for head and neck cancer.
AB  - We report the case of a 67-year-old Caucasian man with unexplained presyncopal
      episodes during radiation therapy for oropharyngeal cancer. 

PMID- 25057401
TI  - Takayasu's arteritis and an elevated antistreptolysin O titre - a potentially
      expensive diagnostic conundrum.
AB  - Takayasu's arteritis is a chronic large vessel vasculitis which may be associated
      with a false positive antistreptolysin O titre. 

PMID- 25057402
TI  - Antiplatelet antibodies in oxaliplatin-induced immune thrombocytopenia.
AB  - Drug-induced immune thrombocytopenia may be potentially fatal; here we report the
      development of severe thrombocytopenia with strong oxaliplatin-dependent
      antiplatelet antibodies. 

PMID- 25057403
TI  - Measuring the acute cardiovascular effects of shisha smoking: a cross-sectional
      study.
AB  - OBJECTIVES: To investigate the acute cardiovascular effects of smoking shisha.
      DESIGN: A cross-sectional study was carried out in six shisha cafes. Participants
      smoked shisha for a period between 45 min (minimum) and 90 min (maximum). The
      same brand of tobacco and coal was used. SETTING: London, UK. PARTICIPANTS:
      Participants were those who had ordered a shisha to smoke and consented to have
      their blood pressure, heart rate and carbon monoxide levels measured. Excluded
      subjects were those who had smoked shisha in the previous 24 h, who smoke
      cigarettes or who suffered from cardiorespiratory problems. MAIN OUTCOME
      MEASURES: Blood pressure was measured using a sphygmomanometer. Pulse was
      measured by palpation of the radial artery. Carbon monoxide levels were obtained
      via a carbon monoxide monitor. These indices were measured before the
      participants began to smoke shisha and after they finished or when the maximum 90
      min time period was reached. RESULTS: Mean arterial blood pressure increased from
      96 mmHg to 108 mmHg (p < 0.001). Heart rate increased from 77 to 91 bpm (p <
      0.001). Carbon monoxide increased from an average of 3 to 35 ppm (p < 0.001). A
      correlation analysis showed no relationship between carbon monoxide and the other
      indices measured. CONCLUSION: The acute heart rate, blood pressure and carbon
      monoxide levels were seen to rise significantly after smoking shisha. The weak
      correlation between carbon monoxide levels and the other variables suggests that
      carbon monoxide levels had not contributed to their significant increase.

PMID- 25057404
TI  - Variations in time to receiving first surgical treatment for breast cancer as a
      function of racial/ethnic background: a cohort study.
AB  - OBJECTIVE: To evaluate surgical treatment delay disparities by race/ethnic group
      in a group of breast cancer patients treated in the New York region. DESIGN:
      Cohort study. SETTING: Two affiliated hospitals in the New York region.
      PARTICIPANTS: Patients admitted at two affiliated hospitals in the New York
      region for breast cancer treatment during 2007-2011. MAIN OUTCOME MEASURE: Time
      to receiving first surgery for breast cancer, defined as the time in days between
      initial diagnosis (biopsy) and definitive surgical treatment (lumpectomy or
      mastectomy). Predicted time to first surgery by race group was also analysed
      using a multivariate linear regression model with adjustments made for several
      demographic and clinical factors. RESULTS: Totally, 3071 patients who were first
      treated with surgery were identified. Racial background was classified as White,
      African American or Asian/other. Overall median time to surgery was 28 days: 28
      days in whites, and 34 and 29 days in African Americans and Asian/others,
      respectively (p = 0.032). Multivariate analyses showed that only African
      Americans, not Asian/others, had significantly increased surgical delay compared
      to whites (p = 0.019). CONCLUSIONS: This study demonstrates significant racial
      differences in surgical delay in a group of breast cancer patients treated in the
      New York region. These differences may reflect tacit attitudes of medical
      providers or processes insensitive to patient educational needs. Additional
      studies may improve our understanding of this delay.

PMID- 25057405
TI  - Subacromial, supracoracoid dislocation of the acromioclavicular joint with
      ipsilateral clavicle fracture: a case report with review of the literature and
      classification.
AB  - A type VI acromioclavicular joint injury with a supracoracoid location of the
      distal end of the clavicle (VIa) may be associated with low energy injuries and,
      in association with a clavicle fracture, can successfully be treated with
      reduction of the dislocation, fixation of the clavicle, and may not require
      reconstruction of the acromioclavicular ligaments. An infracoracoid location
      (VIb) is highly suggestive of a higher energy injury. 

PMID- 25057406
TI  - Early life factors in relation to cardiovascular risk and cardiovascular disease
      in old age in Bergen: a Norwegian retrospective cohort study based on the
      Hordaland Health Study (HUSK).
AB  - OBJECTIVES: The fetal origins of adult disease hypothesis describes associations
      found for fetal or early-life exposures with cardiovascular risk and disease in
      adulthood. The extension or not of these associations into old age has received
      less attention. We investigated if maternal health and family circumstances were
      associated with cardiovascular risk factors and cardiovascular disease (CVD) in
      late life and discuss results in light of possible selection effects and
      measurement error. DESIGN: A retrospective cohort study based on community
      survey. We examined 224 possible associations between anthropometric measures,
      maternal health information and family socioeconomic status at birth versus CVD
      and CVD-related risk factors 72-74 years later. PARTICIPANTS: Of 3341
      participants in a community survey of people aged 72-74 years, we were able to
      trace birth records from a historical archive in a broadly representative
      subsample of 480. SETTING: Bergen, Norway. MAIN OUTCOME MEASURES: Established
      cardiovascular risk factors and indicators of CVD. RESULTS: Only 11 (4.9%) of
      these associations were found to be statistically significant, and no strong or
      consistent patterns in the associations between exposures and outcomes were
      found. CONCLUSIONS: There was little evidence in this relatively elderly sample
      for an association between early life factors and CVD outcomes of clinical or
      public health relevance. Further research is required to confirm the extent to
      which a diminution of early life influences into old age, if genuine, can be
      accounted for by selective mortality, systematic bias or by dilution of effects
      due to competing risk factors.

PMID- 25057407
TI  - Conditions triggering local incident reviews in UK hospital maternity units: A
      national survey.
AB  - OBJECTIVES: In countries, such as the UK, where maternal deaths are rare, reviews
      of other severe complications of pregnancy and the puerperium can provide an
      additional perspective to help learn lessons to improve future care. The
      objective of this survey was to identify the types of incidents which triggered
      local reviews in the UK, in order to inform national safety reporting guidance.
      DESIGN: A national descriptive survey. SETTING: UK. PARTICIPANTS: Consultant-led
      maternity units. MAIN OUTCOME MEASURE: Seventy-one per cent of maternity units
      provided an incident review trigger list. The conditions included were classified
      by two assessors. Incidents that were listed by at least 5% of maternity units
      were reported and compared with incidents recommended for review by the Royal
      College of Obstetricians and Gynaecologists (RCOG). RESULTS: The conditions
      covered were highly variable, although those recommended by the RCOG were most
      highly represented. The most commonly listed conditions that had not been
      recommended for review by the RCOG included inadequate staffing levels (70%),
      cardiac arrest (69%) and maternal sepsis (64%). CONCLUSIONS: Substantial
      variation exists in the types of incident listed for review by maternity units in
      the UK. Importantly, some units are not reviewing cases of severe infective
      complications even though this is a current major concern. Future guidance
      concerning local serious incident review processes should include how the list of
      conditions triggering a review should be managed in the light of changing
      clinical and safety priorities.

PMID- 25057408
TI  - Gestational intestinal obstruction complicated by cortical blindness - a
      multidisciplinary case report.
AB  - Our case highlights the difficulty of diagnosing and managing surgical pathology
      during the advanced stages of pregnancy. 

PMID- 25057409
TI  - Influenza vaccination uptake among people aged over 85 years: an audit of primary
      care practice in the UK.

PMID- 25057410
TI  - Rapidly developing renal milk of calcium in a patient with myelomonocytic
      leukaemia.
AB  - Rapidly developing renal milk of calcium, diagnosed by computed tomography (CT),
      X-ray and ultrasound, should be considered as a rare differential diagnosis in
      patients with apparent ureteric obstruction to prevent unnecessary interventions.

PMID- 25057412
TI  - Optimisation of Cellulase Production by Penicillium funiculosum in a Stirred Tank
      Bioreactor Using Multivariate Response Surface Analysis.
AB  - Increasing interest in the production of second-generation ethanol necessitates
      the low-cost production of enzymes from the cellulolytic complex (endoglucanases,
      exoglucanases, and beta-glucosidases), which act synergistically in cellulose
      breakdown. The present work aimed to optimise a bioprocess to produce these
      biocatalysts from the fungus Penicillium funiculosum ATCC11797. A statistical
      full factorial design (FFD) was employed to determine the optimal conditions for
      cellulase production. The optimal composition of culture media using Avicel (10
      g.L(-1)) as carbon source was determined to include urea (1.2 g.L(-1)), yeast
      extract (1.0 g.L(-1)), KH2PO4 (6.0 g.L(-1)), and MgSO4 .7H2O (1.2 g.L(-1)). The
      growth process was performed in batches in a bioreactor. Using a different FFD
      strategy, the optimised bioreactor operational conditions of an agitation speed
      of 220 rpm and aeration rate of 0.6 vvm allowed the obtainment of an enzyme pool
      with activities of 508 U.L(-1) for FPase, 9,204 U.L(-1) for endoglucanase, and
      2,395 U.L(-1) for beta-glucosidase. The sequential optimisation strategy was
      effective and afforded increased cellulase production in the order from 3.6 to
      9.5 times higher than production using nonoptimised conditions. 

PMID- 25057411
TI  - Duration of type 2 diabetes and very low density lipoprotein levels are
      associated with cognitive dysfunction in metabolic syndrome.
AB  - Type 2 diabetes (T2D) is now recognized as an independent risk factor for
      accelerated cognitive decline and neurological conditions like Alzheimer's
      disease. Less is known about the neurocognitive function of T2D patients with
      comorbid metabolic syndrome, despite their elevated risk for impairment.
      Computerized testing in 47 adults with T2D that met criteria for NCEP metabolic
      syndrome revealed that cognitive impairment was prevalent, including 13% in tests
      of memory, 50% in attention, and 35% in executive function. Partial correlations
      showed that longer duration of diabetes was associated with poorer performance on
      tests of basic attention (r = -0.43), working memory (r = 0.43), and executive
      function (r = 0.42). Strong associations between very low density lipoprotein and
      poor cognitive function also emerged, including tests of set shifting (r = 0.47)
      and cognitive inhibition (r = -0.51). Findings suggest that patients with T2D
      that meet criteria for metabolic syndrome are at high risk for cognitive
      impairment. Prospective studies should look to replicate these findings and
      examine the possible neuroprotective effects of lipid-lowering medication in this
      population. 

PMID- 25057413
TI  - Do DSM-5 eating disorder criteria overpathologize normative eating patterns among
      individuals with obesity?
AB  - BACKGROUND: DSM-5 revisions have been criticized in the popular press for
      overpathologizing normative eating patterns-particularly among individuals with
      obesity. To evaluate the evidence for this and other DSM-5 critiques, we compared
      the point prevalence and interrater reliability of DSM-IV versus DSM-5 eating
      disorders (EDs) among adults seeking weight-loss treatment. METHOD: Clinicians (n
      = 2) assigned DSM-IV and DSM-5 ED diagnoses to 100 participants via routine
      clinical interview. Research assessors (n = 3) independently conferred ED
      diagnoses via Structured Clinical Interview for DSM-IV and a DSM-5 checklist.
      RESULTS: Research assessors diagnosed a similar proportion of participants with
      EDs under DSM-IV (29%) versus DSM-5 (32%). DSM-5 research diagnoses included
      binge eating disorder (9%), bulimia nervosa (2%), subthreshold binge eating
      disorder (5%), subthreshold bulimia nervosa (2%), purging disorder (1%), night
      eating syndrome (6%), and other (7%). Interrater reliability between clinicians
      and research assessors was "substantial" for both DSM-IV (kappa = 0.64, 84%
      agreement) and DSM-5 (kappa = 0.63, 83% agreement). CONCLUSION: DSM-5 ED criteria
      can be reliably applied in an obesity treatment setting and appear to yield an
      overall ED point prevalence comparable to DSM-IV.

PMID- 25057415
TI  - Influence of acquired and genetic risk factors on the prevention, management, and
      treatment of thromboembolic disease.
AB  - Prevention, management, and treatment of venous thromboembolism requires
      understanding of the epidemiology and associated risk factors, particularly in
      recognizing populations warranting prophylaxis, in evaluating patients with high
      risk situations, and in determining the duration of anticoagulation required to
      minimize recurrent thrombosis and to avoid postthrombotic syndrome. The present
      paper reviews recent advances concerning acquired and genetic risk factors for
      venous thrombosis, analyses individual risks related to age, and focuses on
      thrombotic genetic risk factors and the synergistic gene-environment and gene
      gene interactions and their importance in the management and treatment of venous
      thromboembolic disease. 

PMID- 25057414
TI  - Prevalence of obesity in Hail region, KSA: in a comprehensive survey.
AB  - BACKGROUND: Obesity contributes significantly to morbidity and mortality rates
      worldwide. We, therefore, aimed to provide epidemiological data on the prevalence
      of obesity in Hail, Kingdom of Saudi Arabia (KSA). METHODOLOGY: Data were
      collected during cross-sectional survey which included 5000 Saudi selected from
      30 primary health care centers (PHCs) in Hail Region. RESULTS: The overall
      prevalence of obesity in Hail was 63.6%. Moreover, the prevalence of males was
      56.2% and the prevalence of females was 71%. CONCLUSION: Obesity is prevalent in
      the Hail Region which necessitates urgent interventions including health
      education.

PMID- 25057416
TI  - Unintended avulsion of hypertrophic adenoids in posterior nasopharynx: a case
      report of a rare complication caused by nasotracheal intubation.
AB  - The enlarged adenoid serves as a mechanical obstacle on the nasopharynx to
      intricate nasotracheal intubation. No matter what video or direct laryngoscopic
      techniques are applied, nasotracheal tube navigation from the nasal valve area
      through the nasal cavity to the nasopharynx is always blind; trauma is not
      uncommon. Here we report a case of unintended avulsed adenoids that plugged the
      tube tip while the nasotracheal tube blindly navigated through the nasopharyngeal
      space. After failing to insert a bent tip of gum elastic bougie passing through
      the nasopharynx, an alternative method of NTI was performed by mounting the
      nasotracheal tube on a fiberoptic bronchoscope. The nasotracheal tube was
      successfully railroaded along the insertion tube of the fiberscope to the
      trachea. 

PMID- 25057417
TI  - Clinical and Imaging Resolution of Neonatal Hemochromatosis following Treatment.
AB  - Neonatal hemochromatosis (NH) is an acute liver disease associated with both
      hepatic and extrahepatic iron deposition and is a leading cause of neonatal liver
      transplantation. The concept that NH is an alloimmune disease has led to the
      emergence of a new treatment approach utilizing exchange transfusion and
      intravenous immunoglobulin therapy. We present a two-day old neonate with
      progressive liver dysfunction who was diagnosed with NH. Magnetic resonance
      imaging confirmed tissue iron overload. Treatment with intravenous
      immunoglobulins and exchange transfusion led to rapid improvement in liver
      function. Follow-up physical examination at the age of 8 months showed normal
      development and near normal liver function. A repeat abdominal magnetic resonance
      scan at 8 months showed no signs of iron deposition in the liver, pancreas, or
      adrenal glands. The present report provides further support for the use of
      exchange transfusion and immunoglobulin therapy in NH and is the first to
      document resolution of typical iron deposition by magnetic resonance imaging. 

PMID- 25057418
TI  - Unusual T-lymphoblastic blast phase of chronic myelogenous leukemia.
AB  - T-lymphoblastic leukemia/lymphoma (T-ALL) presenting as blast phase of chronic
      myelogenous leukemia (CML-BP) is rare. In patients without history of CML, it is
      difficult to differentiate between CML-BP or de novo T-ALL. Here we reported 2
      unusual cases of T-ALL presenting as CML-BP. Case 1 was a 24-year-old female with
      leukocytosis. Besides T-lymphoblasts (32%), her marrow exhibited some morphologic
      features of CML. Multiple remission or relapsing marrow had never demonstrated
      morphologic features of CML. Despite of imatinib treatment and stem cell
      transplant, she died 2.5 years later. Case 2, a 66-year-old male with diffuse
      lymphadenopathy, showed T-ALL in a lymph node and concurrent CML chronic phase
      (CML-CP) in his marrow. Same BCR-ABL1 fusion transcript with minor breakpoint was
      present in both the lymph node and marrow specimens. Although both cases did not
      have a history of CML, both cases represented T-lymphoblastic CML-BP with unusual
      features: Case 1 is unusual in that it presented as T-ALL with some CML
      morphologic feature but never showed CML-CP in her subsequent marrows biopsies;
      Case 2 is the first reported case of T-lymphoblastic CML-BP harboring BCR-ABL1
      transcript with a minor breakpoint. 

PMID- 25057419
TI  - A Novel Case of Symptomatic BK Viraemia in a Patient Undergoing Treatment for
      Hodgkin Lymphoma.
AB  - Symptomatic BK viral infection in the immunocompromised host is well described,
      most commonly seen in renal transplant recipients, bone marrow transplant
      recipients, and HIV positive patients. The present case describes a novel
      clinical scenario of symptomatic urological BK virus infection in a patient
      receiving treatment for Hodgkin lymphoma. This case highlights the importance of
      casting a wide diagnostic net for adverse events encountered with novel
      therapeutic agents or regimens. 

PMID- 25057420
TI  - Spontaneous uterine perforation of pyometra presenting as acute abdomen.
AB  - Pyometra is the accumulation of pus in the uterine cavity, and spontaneous
      perforation of pyometra resulting in generalized diffuse peritonitis is extremely
      uncommon. We report a rare case of diffuse peritonitis caused by spontaneous
      perforation of pyometra. A 66-year-old postmenopausal woman with diffuse
      abdominal pain and vomiting was admitted to our institution. She had a history of
      mixed connective-tissue disease and had been taking steroids for 20 years. Under
      a diagnosis of generalized peritonitis secondary to perforation of the
      gastrointestinal tract or uterus, supravaginal hysterectomy and bilateral
      salpingo-oophorectomy were performed. Unfortunately, wound dehiscence and
      infection occurred during the postoperative course, which were exacerbated by her
      immunocompromised state. Despite intensive care and a course of antibiotics, the
      patient died of multiple organ failure resulting from sepsis on the 36th
      postoperative day. Although correct diagnosis, early intervention, and proper
      treatment can reduce morbidity and mortality of spontaneous perforation of
      pyometra, if severe infection occurs, this disease can be life threatening for
      immunocompromised hosts. 

PMID- 25057421
TI  - Congenital intralabyrinthine cholesteatoma.
AB  - A patient with a congenital intralabyrinthine cholesteatoma is presented. High
      resolution computerized tomographic scans and intraoperative photomicrographs
      display features of intralabyrinthine extension. We discuss pathogenetic theories
      for the development of congenital intralabyrinthine cholesteatoma. The
      distinction of this condition from congenital cholesteatoma with labyrinthine
      erosion is discussed. 

PMID- 25057422
TI  - Squamous cell carcinoma arising from inverted schneiderian papilloma: a case
      report with oral involvement.
AB  - Inverted Schneiderian papilloma is an uncommon benign tumor that presents
      tendency to recur and propensity to be associated with malignancy in
      approximately 10% of the cases. Some of these lesions are isolated in the
      maxillary sinus, and predominantly affect white males with mean age of 50 years.
      We report a case of squamous cell carcinoma arising from inverted Schneiderian
      papilloma in the maxillary sinus extending to the mouth. The patient was
      submitted to extraction of a maxillary molar tooth four months before the
      exacerbation of the symptoms of nasal airway obstruction and facial enlargement.
      Computed tomography scan revealed a sinonasal mass causing opacification of the
      right maxillary sinus with destruction of the lateral nasal wall and maxillary
      sinus floor. The patient was referred to an oncology center for treatment and
      died from tumor progression one year after the cancer was diagnosed. The
      intention of this report is to alert dentists to include the inverted
      Schneiderian papilloma, either associated with squamous cell carcinoma, or not,
      in the differential diagnosis of maxillary sinus tumors with aggressive behavior,
      which may extend to the oral cavity or involve roots of teeth. 

PMID- 25057423
TI  - Primary atypical carcinoid tumour of the sphenoid sinus rostrum.
AB  - Primary carcinoid tumors of the nasal cavity and sinuses are exceedingly rare. An
      accurate histopathological diagnosis is crucial to optimal investigation and
      management. We present a case of a primary atypical carcinoid tumor arising from
      the sphenoid rostrum without evidence of associated carcinoid syndrome. This rare
      but important differential diagnosis of a nasal tumor is discussed and important
      unique management issues are highlighted. 

PMID- 25057424
TI  - Acute peripheral facial palsy after chickenpox: a rare association.
AB  - Chickenpox, resulting from primary infection by the varicella-zoster virus, is an
      exanthematous disease very common during childhood and with good prognosis.
      However, serious complications, namely, neurological syndromes, may develop
      during its course, especially in risk groups, including adolescents. Peripheral
      facial palsy is a rare neurologic complication that has been previously
      described. Conclusion. We report the case of a teenager with peripheral facial
      palsy as a complication of chickenpox, aiming to increase the awareness of this
      rare association. 

PMID- 25057425
TI  - Cystic meningioma simulating arachnoid cyst: report of an unusual case.
AB  - The purpose of this paper is to show an unusual case of meningioma simulating
      arachnoid cyst on CT scan and MRI, diagnosed in a 63-year-old woman evaluated for
      headache and vision disorders. The meningioma shown is predominantly cystic with
      a small mural nodule enhancing after gadolinium and exhibiting diffusion
      restriction. Cystic portion of the tumor is hypodense on CT, and evidences fluid
      signal intensity on T1- and T2-weighted MR imaging. 

PMID- 25057426
TI  - Intestinal Obstruction due to Bilateral Strangulated Femoral Hernias.
AB  - Introduction. Femoral hernias are at high risk of strangulation due to the narrow
      femoral canal and femoral ring. This can lead to symptoms of obstruction or
      strangulation requiring emergency surgery and possible bowel resection. To our
      knowledge, there is only one previous published report of bilateral strangulated
      femoral hernia. We present our case of this phenomenon. Case Report. An 86-year
      old woman presented with symptoms of small bowel obstruction. Examination
      revealed two tender lumps in the area of the femoral triangle. CT scan revealed
      bilateral femoral hernias. Both hernias were repaired and a small bowel resection
      on the right side was performed with side to side anastomosis. She made an
      uneventful recovery. Conclusion. Bilateral femoral hernias are a rare occurrence
      with only one reported case of bilateral strangulation. Our case highlights the
      importance of meticulous history taking and clinical examination as any delay in
      diagnosis will increase the risk of mortality and morbidity for the patient.
      Hernias should always be considered as a cause if one presents with symptoms of
      abdominal pain or obstruction. 

PMID- 25057427
TI  - Left atrial anatomy relevant to catheter ablation.
AB  - The rapid development of interventional procedures for the treatment of
      arrhythmias in humans, especially the use of catheter ablation techniques, has
      renewed interest in cardiac anatomy. Although the substrates of atrial
      fibrillation (AF), its initiation and maintenance, remain to be fully elucidated,
      catheter ablation in the left atrium (LA) has become a common therapeutic option
      for patients with this arrhythmia. Using ablation catheters, various isolation
      lines and focal targets are created, the majority of which are based on gross
      anatomical, electroanatomical, and myoarchitectual patterns of the left atrial
      wall. Our aim was therefore to review the gross morphological and architectural
      features of the LA and their relations to extracardiac structures. The latter
      have also become relevant because extracardiac complications of AF ablation can
      occur, due to injuries to the phrenic and vagal plexus nerves, adjacent coronary
      arteries, or the esophageal wall causing devastating consequences. 

PMID- 25057428
TI  - A Proposal for Six Sigma Integration for Large-Scale Production of Penicillin G
      and Subsequent Conversion to 6-APA.
AB  - Six Sigma methodology has been successfully applied to daily operations by
      several leading global private firms including GE and Motorola, to leverage their
      net profits. Comparatively, limited studies have been conducted to find out
      whether this highly successful methodology can be applied to research and
      development (R&D). In the current study, we have reviewed and proposed a process
      for a probable integration of Six Sigma methodology to large-scale production of
      Penicillin G and its subsequent conversion to 6-aminopenicillanic acid (6-APA).
      It is anticipated that the important aspects of quality control and quality
      assurance will highly benefit from the integration of Six Sigma methodology in
      mass production of Penicillin G and/or its conversion to 6-APA. 

PMID- 25057430
TI  - Digital pathology: A systematic evaluation of the patent landscape.
AB  - INTRODUCTION: Digital pathology is a relatively new field. Inventors of
      technology in this field typically file for patents to protect their intellectual
      property. An understanding of the patent landscape is crucial for companies
      wishing to secure patent protection and market dominance for their products. To
      our knowledge, there has been no prior systematic review of patents related to
      digital pathology. Therefore, the aim of this study was to systematically
      identify and evaluate United States patents and patent applications related to
      digital pathology. MATERIALS AND METHODS: Issued patents and patent applications
      related to digital pathology published in the United States Patent and Trademark
      Office (USPTO) database (www.uspto.gov) (through January 2014) were searched
      using the Google Patents search engine (Google Inc., Mountain View, California,
      USA). Keywords and phrases related to digital pathology, whole-slide imaging
      (WSI), image analysis, and telepathology were used to query the USPTO database.
      Data were downloaded and analyzed using the Papers application (Mekentosj BV,
      Aalsmeer, Netherlands). RESULTS: A total of 588 United States patents that
      pertain to digital pathology were identified. In addition, 228 patent
      applications were identified, including 155 that were pending, 65 abandoned, and
      eight rejected. Of the 588 patents granted, 348 (59.18%) were specific to
      pathology, while 240 (40.82%) included more general patents also usable outside
      of pathology. There were 70 (21.12%) patents specific to pathology and 57
      (23.75%) more general patents that had expired. Over 120 unique entities
      (individual inventors, academic institutions, and private companies) applied for
      pathology specific patents. Patents dealt largely with telepathology and image
      analysis. WSI related patents addressed image acquisition (scanning and focus),
      quality (z-stacks), management (storage, retrieval, and transmission of WSI
      files), and viewing (graphical user interface (GUI), workflow, slide navigation
      and remote control). An increasing number of recent patents focused on computer
      aided diagnosis (CAD) and digital consultation networks. CONCLUSION: In the last
      2 decades, there have been an increasing number of patents granted and patent
      applications filed related to digital pathology. The number of these patents
      quadrupled during the last decade, and this trend is predicted to intensify based
      on the number of patent applications already published by the USPTO.

PMID- 25057431
TI  - Accuracy of the CellaVision DM96 platform for reticulocyte counting.
AB  - CONTEXT: Many hematology laboratories have adopted semi-automated digital
      platforms for routine use and the evidence supporting their use is increasing.
      AIMS: The CellaVision platforms are among the most thoroughly studied digital
      hematology platforms; we wished to determine the accuracy of CellaVision for
      reticulocyte counting. DESIGN MATERIALS AND METHODS: We compared reticulocyte
      counts performed manually, using the Beckman Coulter LH750 automated analyzer and
      with the CellaVision DM96 platform. We analyzed the results for pair-wise
      correlation and bias, and precision. STATISTICAL ANALYSES USED: Analyses were
      performed using Statistical Package for the Social Sciences software (SPSS),
      including Spearman's rho correlation coefficient, Friedman's two-way Analysis Of
      Variance (ANOVA) for comparison of distributions; bias was compared by way of
      mean and standard deviation. RESULTS: The CellaVision reticulocyte counts
      correlated most strongly with those of the analyzer (often considered the
      benchmark test); the reticulocyte count distributions were noted not to be
      significantly different from each other across all three methods. The mean and
      standard deviation of bias were lowest in the comparison of CellaVision and LH750
      counts. CONCLUSIONS: Our data provide additional support for the accuracy of
      digital hematology applications using the CellaVision DM96 platform.

PMID- 25057429
TI  - Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for
      Lymphoma.
AB  - Lymphomas are cancers that arise from white blood cells and usually present as
      solid tumors. Treatment of lymphoma often involves chemotherapy, and can also
      include radiotherapy and/or bone marrow transplantation. There is an un
      questioned need for more effective therapies and diagnostic tool for lymphoma.
      Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional
      structures are dictated by their sequences. The immense diversity in function and
      structure of nucleic acids enable numerous aptamers to be generated through an
      iterative in vitro selection technique known as Systematic Evolution of Ligands
      by EXponential enrichment (SELEX). Aptamers have several biochemical properties
      that make them attractive tools for use as potential diagnostic and pharmacologic
      agents. Isolated aptamers may directly inhibit the function of target proteins,
      or they can also be formulated for use as delivery agents for other therapeutic
      or imaging cargoes. More complex aptamer identification methods, using whole
      cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect
      them. This review focuses on recent advances in the use of nucleic acid aptamers
      as diagnostic and therapeutic agents and as targeted delivery carriers that are
      relevant to lymphoma. Some representative examples are also discussed.

PMID- 25057432
TI  - Subspecialty surgical pathologist's performances as triage pathologists on a
      telepathology-enabled quality assurance surgical pathology service: A human
      factors study.
AB  - BACKGROUND: The case triage practice workflow model was used to manage incoming
      cases on a telepathology-enabled surgical pathology quality assurance (QA)
      service. Maximizing efficiency of workflow and the use of pathologist time
      requires detailed information on factors that influence telepathologists'
      decision-making on a surgical pathology QA service, which was gathered and
      analyzed in this study. MATERIALS AND METHODS: Surgical pathology report reviews
      and telepathology service logs were audited, for 1862 consecutive telepathology
      QA cases accrued from a single Arizona rural hospital over a 51 month period. Ten
      university faculty telepathologists served as the case readers. Each
      telepathologist had an area of subspecialty surgical pathology expertise (i.e.
      gastrointestinal pathology, dermatopathology, etc.) but functioned largely as a
      general surgical pathologist while on this telepathology-enabled QA service. They
      handled all incoming cases during their individual 1-h telepathology sessions,
      regardless of the nature of the organ systems represented in the real-time
      incoming stream of outside surgical pathology cases. RESULTS: The 10
      participating telepathologists' postAmerican Board of pathology examination
      experience ranged from 3 to 36 years. This is a surrogate for age. About 91% of
      incoming cases were immediately signed out regardless of the subspecialty
      surgical pathologists' area of surgical pathology expertise. One hundred and
      seventy cases (9.13%) were deferred. Case concurrence rates with the provisional
      surgical pathology diagnosis of the referring pathologist, for incoming cases,
      averaged 94.3%, but ranged from 88.46% to 100% for individual telepathologists.
      Telepathology case deferral rates, for second opinions or immunohistochemistry,
      ranged from 4.79% to 21.26%. Differences in concordance rates and deferral rates
      among telepathologists, for incoming cases, were significant but did not
      correlate with years of experience as a practicing pathologist. Coincidental
      overlaps of the area of subspecialty surgical pathology expertise with organ
      related incoming cases did not influence decisions by the telepathologists to
      either defer those cases or to agree or disagree with the referring pathologist's
      provisional diagnoses. CONCLUSIONS: Subspecialty surgical pathologists
      effectively served as general surgical pathologists on a telepathology-based
      surgical pathology QA service. Concurrence rates with incoming surgical pathology
      report diagnoses, and case deferral rates, varied significantly among the 10 on
      service telepathologists. We found no evidence that the higher deferral rates
      correlated with improving the accuracy or quality of the surgical pathology
      reports.

PMID- 25057433
TI  - Assessment of the Self-Determination of Spanish Students with Intellectual
      Disabilities and other Educational Needs.
AB  - The purpose of this study was to assess the self-determination of Spanish high
      school students with Intellectual Disability and other Special Educational Needs
      (SEN). A total of 371 students between 11 and 17 years of age participated in the
      study. Of these, 46.4% (n=171) presented SEN, specifically learning disabilities
      (n=97; 26.2%), borderline and intellectual disability with higher IQ scores
      (n=43; 11.6%) and mild intellectual disability (n=32; 8.6%). The remaining
      students without SEN made up the control group. The assessment was carried out
      using a translated and validated Spanish version of The Arc's Self-Determination
      Scale (Wehmeyer, 1995). This measure had appropriate psychometric properties.
      Students with SEN obtained significantly lower scores than their peers without
      SEN. However, no differences were found in relation to the type of SEN or, more
      specifically, in relation to the presence of intellectual disability. The
      educational implications of the results are discussed.

PMID- 25057434
TI  - Establishing the Medication Safety Research Network of Indiana (Rx-SafeNet):
      Perspectives of Community Pharmacy Employees.
AB  - The objective of this cross-sectional survey was to determine community pharmacy
      employee research project priorities and assess interest levels, barriers, and
      facilitators to joining a new community pharmacy practice-based research network
      (PBRN) and use this information in subsequent PBRN development. One hundred forty
      pharmacists and 40 support staff responded. The majority (72%) of respondents
      were somewhat interested or needed more information to determine their level of
      interest in joining a PBRN; 15% were very interested. While all research topics
      were regarded as important, dispensing errors were rated as the most important.
      Time constraints were considered the greatest barrier to participation. Greater
      knowledge of medication safety, enrichment of patient care, and improved patient
      and provider relationships were considered important reasons for joining a PBRN.
      Responses indicated favorable interest levels and project support from potential
      network members, though education and awareness campaigns are needed to enhance
      community pharmacy employee understanding of and involvement in research and
      PBRNs, specifically the Medication Safety Research Network of Indiana (Rx
      SafeNet), a new network administered by the Purdue University College of
      Pharmacy. While the generalizability of survey results is limited, they were
      useful in determining policies and procedures of the new network. Surveying all
      employees involved in the future PBRN during the network development process is a
      unique approach to developing these types of networks in the U.S. Understanding
      support staff perspectives is important considering the critical role they play
      in project implementation and operations. Emerging PBRNs from any discipline may
      benefit from considering adding this step to their development.

PMID- 25057436
TI  - Role of SCOX in determination of Drosophila melanogaster lifespan.
AB  - In man, COX (cytochrome c oxidase) deficiency is reported to be related to
      mutation of the SCO2 (synthesis of cytochrome c oxidase 2) gene, which encodes
      one of the copper-donor chaperones involved in the assembly of mitochondrial
      cytochrome c oxidase. Such COX deficiency due to the genetic condition leads to
      heart disease and the Leigh syndrome and is frequently fatal in childhood.
      Synthesis of cytochrome c oxidase X (SCOX) is a Drosophila orthologue of human
      SCO2. Here, we generated SCOX-knockdown flies and the full length SCOX transgenic
      flies to investigate the in vivo roles of SCOX. Our results demonstrated
      knockdown of SCOX gene in all cells and tissues to be associated with lethality
      at larval or pupal stages and this correlated with a decrease in ATP level. In
      contrast, the full length SCOX transgenic flies showed a longer lifespan than
      wild type flies and control flies carrying Act5C-GAL4 alone and this correlated
      with an increase in ATP level. Finally, when cultured on paraquat-added medium,
      full length SCOX transgenic flies also exhibited an elongated lifespan.
      Therefore, we hypothesized that SCOX plays an important role in ATP production
      and consumption, which helps to prevent production of mitochondrial reactive
      oxygen species and/or impairment of mitochondrial activity under oxidative
      stress. 

PMID- 25057435
TI  - Role of SOX family of transcription factors in central nervous system tumors.
AB  - SOX genes are developmental regulators with functions in the instruction of cell
      fate and maintenance of progenitor's identity during embryogenesis. They play
      additional roles during tissue homeostasis and regeneration in adults
      particularly in the Central Nervous System (CNS). In the last years a growing
      number of evidences has shown that mutations and dysfunction of SOX factors are
      implicated in several human diseases, including a variety of cancers. In this
      review, we will summarize the current knowledge about SOX family in CNS tumors
      and their role in the origin and maintenance of the subpopulation of cancer stem
      cells in these tumors. 

PMID- 25057437
TI  - Distinct breast cancer subtypes in women with early-onset disease across races.
AB  - BACKGROUND: Racial disparities among breast cancer (BCa) patients are known but
      not well studied in early-onset BCa. We analyzed molecular subtypes in early
      onset BCa across five major races. METHODS: A total of 2120 cases were included
      from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and
      Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic
      subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa
      (TNBC) subtypes. Data was stratified according to race and age as younger/early
      onset group (40-years and younger) and older group (50-years and older). RESULTS:
      In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in
      Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2
      over-expression subtype also was highest in Indian women, followed by Hispanic,
      Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly
      higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p =
      0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was
      most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA,
      NHW and Chinese women. These results were based on statistical analysis with the
      mean of older group populations. CONCLUSIONS: These results show significant
      disparities in receptor subtypes across races. This study will contribute in
      developing optimal clinical trial protocols and personalized management
      strategies for early-onset BCa patients.

PMID- 25057438
TI  - Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR
      assessment justified?
AB  - BACKGROUND: Triple negative breast carcinomas (TNBC) do not benefit from hormonal
      or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest
      is escalating in a subset of these tumors that are androgen receptor (AR)
      positive with potential benefit from anti-androgen therapy. Against this
      background, the frequency of AR expression alone and in combination with other
      markers and morphologic features was assessed to identify TNBC subtypes for
      targeted therapy. METHODS: 400 consecutive invasive mammary carcinomas with known
      estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and
      HER2 status were selected for study. The frequency of AR positivity alone or in
      combination with other markers was recorded with specific attention to the
      morphology of AR+ TNBCs. Ki67 was evaluated in selected group of cases. ASCO/CAP
      guidelines were used for interpretation of the various biomarkers. RESULTS: Of
      the 400 tumors, 32 (8%) carcinomas were quadruple negative (ER-, PR-, AR-, Her2
      ), while 50 tumors (12.5%) were triple negative (ER-, PR-, Her2-); 18 (36%) of
      the triple negative tumors were AR positive and 10 (55%) of these were classic
      apocrine carcinomas. Fourteen cases, all apocrine carcinomas, were AR and Her2
      positive. All 32 QN carcinomas were poorly differentiated and they had the
      highest Ki67 labeling index. CONCLUSION: The relatively high proportion of AR+
      tumors (36%) among the 50 triple negative carcinomas is an important finding in
      support of routine assessment of AR in at least all TNBCs and apocrine carcinomas
      as a potential target for therapy.

PMID- 25057440
TI  - Pre-tumor exercise decreases breast cancer in old mice in a distance-dependent
      manner.
AB  - Epidemiological evidence supports a protective effect of physical activity for
      breast cancer but pre-clinical studies are needed to help define the underlying
      mechanisms in an age-related manner. We utilized 18-month old BALB/c mice
      injected in the mammary fat pad with syngeneic 4T1 tumor cells as a model of
      invasive breast cancer. A negative correlation was observed between daily
      distance ran, prior to tumor injection, and absolute tumor mass measured at
      necropsy (Pearson's r = -0.89, P = 0.0066, R(2) = 0.80). A correlation was also
      observed between distance ran before tumor implant and the histological score for
      mitotic index (Pearson's r = -0.85, P = 0.034, R(2) = 0.72). Runners showed an
      increased respiratory exchange ratio during the light cycle (P = 0.029)
      suggesting that voluntary running shifted resting substrate metabolism toward
      glucose oxidation, relative to lipid oxidation. The shift in substrate metabolism
      was significantly different from baseline for both groups of animals, indicating
      that the tumor burden might have been responsible. The observations from this
      study indicate that running longer distances is associated with decreased breast
      tumor burden in old mice, suggesting that physiological factors generated by
      exercising before tumor onset are protective against tumor progression. The
      mechanisms for this protective effect are not known but the data show that older
      mice are useful models to address specific questions in cancer research and
      support further studies on the ability of exercise training to protect older
      women at risk for breast cancer. 

PMID- 25057439
TI  - Co-expression of RAGE and HMGB1 is associated with cancer progression and poor
      patient outcome of prostate cancer.
AB  - Receptor for advanced glycation end products (RAGE), along with its ligand high
      mobility group box 1 (HMGB1), is believed to play an important role in prostate
      cancer. The aim of this retrospective study was to investigate the expression of
      RAGE and HMGB1 and their clinical impact on prostate cancer progression and
      prognosis. The expression of RAGE and HMGB1 was assessed by immunohistochemistry
      in cancer lesions from 85 confirmed prostate cancer cases. We determined the
      potential association between the expression level of these two proteins and the
      clinicopathological features and overall patient survival. RAGE and HMGB1 were
      expressed in 78.8% (67/85) and 68.2% (58/85) cases of prostate cancer,
      respectively, and in the majority (54/85) of cases, these two proteins were co
      expressed. There was a strong correlation between RAGE and HMGB1 expressions
      (P<0.001). The expression of RAGE, HMGB1 and their co-expression were all
      associated with advanced tumor clinical stage (P<0.05 for all). RAGE expression
      was also associated with the prostate specific antigen (PSA) level (P=0.014).
      However, neither the individual expression of those genes nor their co-expression
      was significantly related with age or Gleason score. The co-expression of RAGE
      and HMGB1 was associated with poor overall survival in patients with stage III
      and IV prostate cancer (P=0.047). These results suggest that the expression of
      RAGE and HMGB1 is associated with the progression and poor prognosis of prostate
      cancer. RAGE and HMGB1 could be new prognostic biomarkers for prostate cancer as
      well as molecular target for novel forms of therapies. 

PMID- 25057441
TI  - Risk stratification of prostate cancer patients based on EPS-urine zinc content.
AB  - The early detection of prostate cancer is a life-saving event in patients
      harboring potentially aggressive disease. With the development of malignancy
      there is a dramatic reduction in the zinc content of prostate tissue associated
      with the inability of cancer cells to accumulate the ion. In the current study,
      we utilized endogenous zinc as a diagnostic biomarker for prostate cancer. We
      employed a novel fluorescent sensor for mobile zinc (ZPP1) to measure the
      concentration of zinc in thirty-nine patient samples of expressed prostatic
      secretion (EPS) in urine. We estimated the probability of classifying a subject
      as benign, low-risk, or high-risk as functions of the diagnostic test results
      using a non-informative prior Bayesian approach. Permutation tests and other non
      parametric tests were also used. We demonstrated a significant trend in zinc
      score with disease and with disease risk (P = 0.03), and lack of a significant
      correlation between zinc score and PSA. We also showed that the proposed
      diagnostic is potentially superior to PSA for detecting high-risk disease.
      Considering that risk stratification represents an important unmet need, our
      method should advance the field of prostate cancer diagnostics and treatment
      planning. 

PMID- 25057442
TI  - Genome-wide prediction of cancer driver genes based on SNP and cancer SNV data.
AB  - Identifying cancer driver genes and exploring their functions are essential and
      the most urgent need in basic cancer research. Developing efficient methods to
      differentiate between driver and passenger somatic mutations revealed from large
      scale cancer genome sequencing data is critical to cancer driver gene discovery.
      Here, we compared distinct features of SNP with SNV data in detail and found that
      the weighted ratio of SNV to SNP (termed as WVPR) is an excellent indicator for
      cancer driver genes. The power of WVPR was validated by accurate predictions of
      known drivers. We ranked most of human genes by WVPR and did functional analyses
      on the list. The results demonstrate that driver genes are usually highly
      enriched in chromatin organization related genes/pathways. And some protein
      complexes, such as histone acetyltransferase, histone methyltransferase,
      telomerase, centrosome, sin3 and U12-type spliceosomal complexes, are hot spots
      of driver mutations. Furthermore, this study identified many new potential driver
      genes (e.g. NTRK3 and ZIC4) and pathways including oxidative phosphorylation
      pathway, which were not deemed by previous methods. Taken together, our study not
      only developed a method to identify cancer driver genes/pathways but also
      provided new insights into molecular mechanisms of cancer development. 

PMID- 25057443
TI  - Driving DNA transposition by lentiviral protein transduction.
AB  - Gene vectors derived from DNA transposable elements have become powerful
      molecular tools in biomedical research and are slowly moving into the clinic as
      carriers of therapeutic genes. Conventional uses of DNA transposon-based gene
      vehicles rely on the intracellular production of the transposase protein from
      transfected nucleic acids. The transposase mediates mobilization of the DNA
      transposon, which is typically provided in the context of plasmid DNA. In recent
      work, we established lentiviral protein transduction from Gag precursors as a new
      strategy for direct delivery of the transposase protein. Inspired by the natural
      properties of infecting viruses to carry their own enzymes, we loaded lentivirus
      derived particles not only with vector genomes carrying the DNA transposon vector
      but also with hundreds of transposase subunits. Such particles were found to
      drive efficient transposition of the piggyBac transposable element in a range of
      different cell types, including primary cells, and offer a new transposase
      delivery approach that guarantees short-term activity and limits potential
      cytotoxicity. DNA transposon vectors, originally developed and launched as a non
      viral alternative to viral integrating vectors, have truly become viral. Here, we
      briefly review our findings and speculate on the perspectives and potential
      advantages of transposase delivery by lentiviral protein transduction.

PMID- 25057444
TI  - Something new to explore: Plant viruses infecting and inducing gene silencing in
      filamentous fungi.
AB  - Functional genomics in plants has been facilitated greatly by the use of plant
      viruses to carry segments of host genes that can then promote the silencing of
      the RNAs expressed from the corresponding host genes; a process called virus
      induced gene silencing (VIGS). The silencing of genes in filamentous fungi is
      either technically more problematic or labor-intensive, especially if transgenic
      plants need to be generated first. However, a recent paper from our team
      demonstrated that a plant virus could infect three related fungal species, as
      well as express a reporter gene ectopically, and also silence the correspondingly
      expressed reporter transgene. The gene expression and RNA silencing of the
      reporter gene was maintained for six passages in culture and also persisted in
      plants infected by the virus-infected fungus. Here, we consider how the virus can
      enter and migrate within the fungus, whether the virus can move back and forth
      between the fungus and the plant and the ramifications of this, the prospects for
      VIGS being used to silence fungal endogenes and possible biotechnological or
      therapeutic applications of using plant viruses for expressing foreign proteins
      in fungi or silencing fungal endogenes.

PMID- 25057445
TI  - Functional comparison of single-chain and two-chain anti-CD3-based bispecific
      antibodies in gene immunotherapy applications.
AB  - Gene therapy to achieve in vivo secretion of recombinant anti-CD3 x anti-tumor
      bispecific antibodies in cancer patients is being explored as a strategy to
      counterbalance rapid renal elimination, thereby sustaining levels of bispecific
      antibodies in the therapeutic range. Here, we performed a comparative analysis
      between single- and two-chain configurations for anti-CD3 x anti-CEA
      (carcinoembryonic antigen) bispecific antibodies secreted by genetically-modified
      human cells. We demonstrate that tandem single-chain variable fragment (scFv)
      antibodies and two-chain diabodies are expressed as soluble secreted proteins
      with similar yields. However, we found significant differences in their
      biological functionality (i.e., antigen binding) and in their ability to induce
      non-specific T cell activation. Whereas single-chain tandem scFvs induced human T
      cell activation and proliferation in an antigen-independent manner, secreted two
      chain diabodies exerted almost no proliferative stimulus when human T cells were
      cultured alone or in co-cultures with CEA negative cells. Thus, our data suggest
      that two-chain diabodies are preferable to single-chain tandem scFvs for
      immunotherapeutic strategies comprising in vivo secretion of bispecific
      antibodies aiming to recruit and activate anticancer specific lymphocytic
      effector T cells.

PMID- 25057446
TI  - A clinically useful approach to enhance immunological memory and antitumor
      immunity.
AB  - Persistence of vaccine-induced immune responses, not the initial magnitude, best
      correlates with protective antitumor immunity. In mice, oligonucleotide aptamer
      targeted siRNA inhibition of mammalian target of rapamycin (mTOR) activity in
      activated CD8+ T cells promotes their differentiation into functionally competent
      memory cells leading to enhanced antitumor immunity, a protective effect superior
      to that of non-targeted administration of the mTOR inhibitor rapamycin.

PMID- 25057447
TI  - Epigenetic remodeling combined with photodynamic therapy elicits anticancer
      immune responses.
AB  - Photodynamic therapy has been shown to induce strong immunity against tumor cells
      expressing exogenous tumor-associated antigens (TAAs), including P1A antigen.
      Cancer cells can evade the immune system by epigenetic silencing of TAAs, while
      DNA methyltransferase inhibitors, such as 5-aza-2'-deoxycytidine (5-aza-dC) can
      restore the expression of silenced or downregulated TAA. Thus, epigenetic
      remodeling with 5-aza-dC combined with PDT can elicit robust and durable
      antitumor immunity.

PMID- 25057448
TI  - Immunosurveillance markers may predict patients who can discontinue imatinib
      therapy without relapse.
AB  - Tyrosine kinase inhibitors have dramatically improved the treatment of chronic
      myeloid leukemia. Recent evidence revealed that some patients with chronic
      myeloid leukemia can stop imatinib without relapse after achieving a complete
      molecular response. This review discusses the possible predictive markers to
      identify these patients who can stop imatinib without relapse.

PMID- 25057449
TI  - Role of cancer stem cell-associated inflammation in creating pro-inflammatory
      tumorigenic microenvironments.
AB  - We identify novel mechanisms whereby chemoresistance enables cancer stem cells to
      create pro-inflammatory tumor microenvironments. Chemoresistant cancer stem cells
      promote M2 macrophage differentiation through interferon-regulatory factor-5
      (IRF5)- and macrophage-colony stimulating factor (M-CSF)-dependent mechanisms and
      produce various other cell-signaling factors that together fuel inflammation
      driven carcinogenesis. These findings clarify a molecular pathway linking cancer
      "stemness" and pro-tumor inflammation in an immunosuppressive niche.

PMID- 25057450
TI  - Menage a trois: Sustained therapeutic anti-tumor immunity requires multiple
      partners in malignant glioma.
AB  - Glioblastoma is an aggressive primary brain cancer. Given our interest in novel
      immunotherapies, we have recently shown that inhibiting CTLA-4, PD-L1 and IDO
      results in a dramatic survival advantage in mice with brain tumors. Our
      preclinical study supports the rapid translation of this approach into phase I
      clinical trial.

PMID- 25057451
TI  - Location, location, location: The relationship of anatomic site, antigen
      expression, and T-cell infiltration in human melanoma metastases.
AB  - Metastatic cell heterogeneity presents a significant obstacle to the development
      of targeted molecular and immunotherapeutics. Profiling of melanocyte
      differentiation antigens has revealed a nonstochastic, site-specific pattern of
      expression in metastases that was highest in brain, intermediate in soft
      tissues/lymph nodes, and lowest in visceral sites. Site-specific antigen
      heterogeneity, thus, is an important confounding factor to consider when
      assessing the potential efficacy of antigen-specific therapies.

PMID- 25057452
TI  - Type II natural killer T cells foster the antitumor activity of CpG
      oligodeoxynucleotides.
AB  - Type II natural killer T (NKT) cells in cancer immunity are typically associated
      with suppression of tumor immunosurveillance through secretion of IL-13. We
      previously demonstrated that CpG oligonucleotide therapy activated Type II NKT
      cells to produce T helper type 1 (Th1) rather than T helper type 2 (Th2)
      cytokines. This cytokine skewing may manifest in Type II NKT cell antitumor
      properties in an immunotherapeutic setting.

PMID- 25057453
TI  - Falling asleep after a big meal: Neuronal regulation of satiety.
AB  - C. elegans has become an ideal model to study genetics of appetite control and
      energy metabolism because of its robust conservation in molecular mechanisms
      underlying appetite control and in regulation of the relevant feeding behavior.
      Satiety behavior in worms in particular shows striking similarities to that in
      mammals, as a worm becomes quiescent after a big meal, mimicking post-prandial
      sleep in mammals. Here we review our recent finding regarding the neuronal
      regulation of the behavior and the implication of the finding such as cyclicity
      of behavioral states. Based on the finding, we propose a rather speculative but
      intriguing view of how metabolism could link to post-prandial sleep. 

PMID- 25057454
TI  - Crossover recombination mediated by HIM-18/SLX4-associated nucleases.
AB  - Meiosis is a specialized cell division program that results in the formation of
      haploid gametes (i.e., sperm and eggs) from diploid parental cells, and is
      essential for all sexually reproducing organisms. Crossover formation, the
      reciprocal exchange of genetic information during recombination, is critical for
      accurate meiotic chromosome segregation. Misregulation of crossover formation
      leads to genomic instability and aneuploidy (cells with the incorrect number of
      chromosomes), resulting in tumorigenesis, birth defects, miscarriages, and
      infertility in humans. Recently, a shuriken/Swiss army knife-like multi-nuclease
      complex has been implicated in processing various types of DNA repair
      intermediates. However, how these nucleases coordinate their functions during
      repair remained unclear. Our studies in C. elegans revealed genetic redundancies
      between these nucleases for meiotic crossover formation and that they promote
      distinct crossover control at different chromosome regions. Specifically, XPF-1
      acts redundantly with both MUS-81 and SLX-1 to resolve Holliday junction
      recombination intermediates into crossover products at designated future
      crossover sites on chromosome arms. In contrast, SLX-1 is required for
      suppression of crossovers at the center region of chromosomes. Altogether, our
      studies have shed light on the interplay between structure-specific endonucleases
      and uncovered their ability to exert either positive or negative meiotic
      crossover control on a chromosome region-specific basis. 

PMID- 25057455
TI  - Neural Correlates of Developmental Speech and Language Disorders: Evidence from
      Neuroimaging.
AB  - Disorders of speech and language arise out of a complex interaction of genetic,
      environmental, and neural factors. Little is understood about the neural bases of
      these disorders. Here we systematically reviewed neuroimaging findings in Speech
      disorders (SD) and Language disorders (LD) over the last five years (2008-2013;
      10 articles). In participants with SD, structural and functional anomalies in the
      left supramarginal gyrus suggest a possible deficit in sensory feedback or
      integration. In LD, cortical and subcortical anomalies were reported in a
      widespread language network, with little consistency across studies except in the
      superior temporal gyri. In summary, both functional and structural anomalies are
      associated with LD and SD, including greater activity and volumes relative to
      controls. The variability in neuroimaging approach and heterogeneity within and
      across participant samples restricts our full understanding of the neurobiology
      of these conditions- reducing the potential for devising novel interventions
      targeted at the underlying pathology.

PMID- 25057456
TI  - High level expression of a glutamate-gated chloride channel gene in reproductive
      tissues of Brugia malayi may explain the sterilizing effect of ivermectin on
      filarial worms.
AB  - Glutamate-gated chloride channels (GluCl) are targets for avermectin/milbemycin
      (A/M) anthelmintics such as ivermectin that cause paralysis of somatic and
      pharyngeal muscles in gastrointestinal nematodes. Ivermectin is useful for
      onchocerciasis control programs because of its activity against microfilariae
      that often cause ocular disease and severe dermatitis. However, mechanisms
      responsible for reduced microfilaria production by adult worms following
      ivermectin treatment are poorly understood. We synthesized subunit-specific RNA
      probes for the Brugia malayi GluCl gene avr-14 (BmAVR-14) to localize expression
      of this gene in adult filarial worms. Both subunits of BmAVR-14 exhibited very
      similar expression patterns. In female worms, strong expression signals were
      detected in the ovary, developing embryos and lateral hypodermal chords, with
      moderate expression in the uterus wall adjacent to stretched microfilariae. These
      genes were also highly expressed in adult male worms (in spermatogonia, in the
      wall of the vas deferens, and in the lateral chords, but not in mature
      spermatozoa). In addition, avr-14 was highly expressed in somatic muscles
      adjacent to the terminal end of the vas deferens which contains mature sperm.
      These results show that avr-14 is highly expressed in B. malayi developing
      embryos and reproductive tissues, and they provide evidence for the involvement
      of GluCl in gamete production and embryogenesis in filarial worms. This may
      explain the observed suppression of microfilaria (Mf) production by female worms
      following treatment with avermectin/milbemycin anthelmintics. 

PMID- 25057457
TI  - Drug-efflux and target-site gene expression patterns in Haemonchus contortus
      larvae able to survive increasing concentrations of levamisole in vitro.
AB  - While there is some evidence that changes in nicotinic acetylcholine receptor
      (nAChR) subunits confer resistance to levamisole in gastrointestinal helminth
      parasites, the exact nature of the resistance mechanism(s) is unclear. We
      utilised the presence of a resistant fraction within the Wallangra 2003 isolate
      of Haemonchus contortus larvae in order to subdivide the population into three
      subpopulations of larvae able to survive increasing concentrations of the drug.
      We then measured gene expression levels in the subpopulations and the larval
      population as a whole, focusing on genes encoding the subunit components of
      levamisole-sensitive receptors, genes encoding ancillary proteins involved in
      receptor assembly, and P-glycoprotein (P-gp) genes. The subpopulation surviving
      the lowest levamisole concentration showed increases of 1.5- to 3-fold in a
      number of P-gp genes (Hco-pgp-3, -4, -10, and -14) alongside unchanged receptor
      genes, compared to the whole Wallangra larval population. On the other hand, the
      subpopulation surviving the intermediate levamisole concentration showed an
      increase in only a single P-gp (Hco-pgp-14), alongside decreases in some receptor
      subunit (Hco-unc-63a) and ancillary protein genes (Hco-unc-50, Hco-ric-3.1 and
      3.1). The subpopulation surviving the highest levamisole concentration showed
      further decreases in receptor subunit genes (Hco-unc-63a and Hco-unc-29 paralogs)
      as well as genes involved in receptor assembly (Hco-unc-74, Hco-unc-50, Hco-ric
      3.1 and 3.1), alongside no increased P-gp gene levels. This suggests a biphasic
      pattern of drug resistance in the larvae of this worm isolate, in which a non
      specific P-gp-mediated mechanism confers low levels of resistance, while higher
      level resistance is due to altered receptor subunit composition as a result of
      changes in both subunit composition and in the levels of proteins involved in
      receptor assembly. 

PMID- 25057458
TI  - microRNAs of parasitic helminths - Identification, characterization and potential
      as drug targets.
AB  - microRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional
      gene regulation. They were first identified in the free-living nematode
      Caenorhabditis elegans, where the miRNAs lin-4 and let-7 were shown to be
      essential for regulating correct developmental progression. The sequence of let-7
      was subsequently found to be conserved in higher organisms and changes in
      expression of let-7, as well as other miRNAs, are associated with certain
      cancers, indicating important regulatory roles. Some miRNAs have been shown to
      have essential functions, but the roles of many are currently unknown. With the
      increasing availability of genome sequence data, miRNAs have now been identified
      from a number of parasitic helminths, by deep sequencing of small RNA libraries
      and bioinformatic approaches. While some miRNAs are widely conserved in a range
      of organisms, others are helminth-specific and many are novel to each species.
      Here we review the potential roles of miRNAs in regulating helminth development,
      in interacting with the host environment and in development of drug resistance.
      Use of fluorescently-labeled small RNAs demonstrates uptake by parasites, at
      least in vitro. Therefore delivery of miRNA inhibitors or mimics has potential to
      alter miRNA activity, providing a useful tool for probing the roles of miRNAs and
      suggesting novel routes to therapeutics for parasite control. 

PMID- 25057460
TI  - Uptake of benzimidazoles by Trichuris suis in vivo in pigs.
AB  - It is recognized that the clinical efficacy of single dose benzimidazoles (BZs)
      against the nematode, Trichuris suis of pigs and the closely related Trichuris
      trichiura in humans is only poor to moderate. Recent in vitro studies have
      indicated that a low uptake of fenbendazole (FBZ) in T. suis may be responsible
      for its poor efficacy. The aim of this study was to investigate this hypothesis
      by measuring the concentrations of FBZ and its metabolites, oxfendazole (OXF) and
      FBZ sulphone (FBZSO2), in T. suis isolated from FBZ treated pigs and in plasma of
      the pigs. The highest concentration of FBZ measured in T. suis was 66.6 pmol/mg
      dry worm tissue which was approximately half of what was measured in a previous
      in vitro study. The correlation between drug concentrations in plasma and in T.
      suis worms was highly positive for OXF (r = 0.93, P = 0.0007) and FBZSO2 (r =
      0.85, P = 0.007), but no correlation was found for FBZ. This study shows that the
      low uptake of FBZ observed for T. suis in vitro, also takes place in vivo. The
      high and significant correlations between OXF and FBZSO2 concentrations in plasma
      of the pigs and T. suis (and the lack of this correlation for FBZ) suggests that
      the metabolites reach the worms via the blood-enterocyte interface while FBZ
      primarily reaches the worms via the intestinal lumen of the host. 

PMID- 25057462
TI  - Quantitative proteomic analysis of amphotericin B resistance in Leishmania
      infantum.
AB  - Amphotericin B (AmB) in its liposomal form is now considered as either first- or
      second-line treatment against Leishmania infections in different part of the
      world. Few cases of AmB resistance have been reported and resistance mechanisms
      toward AmB are still poorly understood. This paper reports a large-scale
      comparative proteomic study in the context of AmB resistance. Quantitative
      proteomics using stable isotope labeling of amino acids in cell culture (SILAC)
      was used to better characterize cytoplasmic and membrane-enriched (ME) proteomes
      of the in vitro generated Leishmania infantum AmB resistant mutant AmB1000.1. In
      total, 97 individual proteins were found as differentially expressed between the
      mutant and its parental sensitive strain (WT). More than half of these proteins
      were either metabolic enzymes or involved in transcription or translation
      processes. Key energetic pathways such as glycolysis and TCA cycle were up
      regulated in the mutant. Interestingly, many proteins involved in reactive oxygen
      species (ROS) scavenging and heat-shock proteins were also up-regulated in the
      resistant mutant. This work provides a basis for further investigations to
      understand the roles of proteins differentially expressed in relation with AmB
      resistance. 

PMID- 25057461
TI  - Idiosyncratic quinoline central nervous system toxicity: Historical insights into
      the chronic neurological sequelae of mefloquine.
AB  - Mefloquine is a quinoline derivative antimalarial which demonstrates promise for
      the treatment of schistosomiasis. Traditionally employed in prophylaxis and
      treatment of chloroquine-resistant Plasmodium falciparum malaria, recent changes
      to the approved European and U.S. product labeling for mefloquine now warn of a
      risk of permanent and irreversible neurological sequelae including vertigo, loss
      of balance and symptoms of polyneuropathy. The newly described permanent nature
      of certain of these neurological effects challenges the conventional belief that
      they are due merely to the long half-life of mefloquine and its continued
      presence in the body, and raises new considerations for the rational use of the
      drug against parasitic disease. In this opinion, it is proposed that many of the
      reported lasting adverse neurological effects of mefloquine are consistent with
      the chronic sequelae of a well characterized but idiosyncratic central nervous
      system (CNS) toxicity syndrome (or toxidrome) common to certain historical
      antimalarial and antiparasitic quinolines and associated with a risk of permanent
      neuronal degeneration within specific CNS regions including the brainstem. Issues
      in the development and licensing of mefloquine are then considered in the context
      of historical awareness of the idiosyncratic CNS toxicity of related quinoline
      drugs. It is anticipated that the information presented in this opinion will aid
      in the future clinical recognition of the mefloquine toxidrome and its chronic
      sequelae, and in informing improved regulatory evaluation of mefloquine and
      related quinoline drugs as they are explored for expanded antiparasitic use and
      for other indications. 

PMID- 25057459
TI  - Drug repurposing and human parasitic protozoan diseases.
AB  - Parasitic diseases have an enormous health, social and economic impact and are a
      particular problem in tropical regions of the world. Diseases caused by protozoa
      and helminths, such as malaria and schistosomiasis, are the cause of most
      parasite related morbidity and mortality, with an estimated 1.1 million combined
      deaths annually. The global burden of these diseases is exacerbated by the lack
      of licensed vaccines, making safe and effective drugs vital to their prevention
      and treatment. Unfortunately, where drugs are available, their usefulness is
      being increasingly threatened by parasite drug resistance. The need for new drugs
      drives antiparasitic drug discovery research globally and requires a range of
      innovative strategies to ensure a sustainable pipeline of lead compounds. In this
      review we discuss one of these approaches, drug repurposing or repositioning,
      with a focus on major human parasitic protozoan diseases such as malaria,
      trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis. 

PMID- 25057463
TI  - Enzymology of the nematode cuticle: A potential drug target?
AB  - All nematodes possess an external structure known as the cuticle, which is
      crucial for their development and survival. This structure is composed primarily
      of collagen, which is secreted from the underlying hypodermal cells. Extensive
      studies using the free-living nematode Caenorhabditis elegans demonstrate that
      formation of the cuticle requires the activity of an extensive range of enzymes.
      Enzymes are required both pre-secretion, for synthesis of component proteins such
      as collagen, and post-secretion, for removal of the previous developmental stage
      cuticle, in a process known as moulting or exsheathment. The excretion/secretion
      products of numerous parasitic nematodes contain metallo-, serine and cysteine
      proteases, and these proteases are conserved across the nematode phylum and many
      are involved in the moulting/exsheathment process. This review highlights the
      enzymes required for cuticle formation, with a focus on the post-secretion
      moulting events. Where orthologues of the C. elegans enzymes have been identified
      in parasitic nematodes these may represent novel candidate targets for future
      drug/vaccine development. 

PMID- 25057464
TI  - Tomato carotenoid cleavage dioxygenases 1A and 1B: Relaxed double bond
      specificity leads to a plenitude of dialdehydes, mono-apocarotenoids and
      isoprenoid volatiles.
AB  - The biosynthetic processes leading to many of the isoprenoid volatiles released
      by tomato fruits are still unknown, though previous reports suggested a clear
      correlation with the carotenoids contained within the fruit. In this study, we
      investigated the activity of the tomato (Solanum lycopersicum) carotenoid
      cleavage dioxygenase (SlCCD1B), which is highly expressed in fruits, and of its
      homolog SlCCD1A. Using in vitro assays performed with purified recombinant
      enzymes and by analyzing products formed by the two enzymes in carotene
      accumulating Escherichia coli strains, we demonstrate that SlCCD1A and, to a
      larger extent, SlCCD1B, have a very relaxed specificity for both substrate and
      cleavage site, mediating the oxidative cleavage of cis- and all-trans-carotenoids
      as well as of different apocarotenoids at many more double bonds than previously
      reported. This activity gives rise to a plenitude of volatiles, mono
      apocarotenoids and dialdehyde products, including cis-pseudoionone, neral,
      geranial, and farnesylacetone. Our results provide a direct evidence for a
      carotenoid origin of these compounds and point to CCD1s as the enzymes catalyzing
      the formation of the vast majority of tomato isoprenoid volatiles, many of which
      are aroma constituents. 

PMID- 25057465
TI  - Anatomical and diffusion MRI of deep gray matter in pediatric spina bifida.
AB  - Individuals with spina bifida myelomeningocele (SBM) exhibit brain abnormalities
      in cortical thickness, white matter integrity, and cerebellar structure. Little
      is known about deep gray matter macro- and microstructure in this population. The
      current study utilized volumetric and diffusion-weighted MRI techniques to
      examine gray matter volume and microstructure in several subcortical structures:
      basal ganglia nuclei, thalamus, hippocampus, and amygdala. Sixty-six children and
      adolescents (ages 8-18; M = 12.0, SD = 2.73) with SBM and typically developing
      (TD) controls underwent T1- and diffusion-weighted neuroimaging. Microstructural
      results indicated that hippocampal volume was disproportionately reduced, whereas
      the putamen volume was enlarged in the group with SBM. Microstructural analyses
      indicated increased mean diffusivity (MD) and fractional anisotropy (FA) in the
      gray matter of most examined structures (i.e., thalamus, caudate, hippocampus),
      with the putamen exhibiting a unique pattern of decreased MD and increased FA.
      These results provide further support that SBM differentially disrupts brain
      regions whereby some structures are volumetrically normal whereas others are
      reduced or enlarged. In the hippocampus, volumetric reduction coupled with
      increased MD may imply reduced cellular density and aberrant organization.
      Alternatively, the enlarged volume and significantly reduced MD in the putamen
      suggest increased density. 

PMID- 25057468
TI  - Very Low Birth Weight Infant Necessitating Nissen Fundoplication for Weaning off
      the Mechanical Ventilator.
AB  - Gastro-esophageal reflux (GER) is one of the common problems of neonatal
      intensive care units. Although this condition does not always need to be treated,
      it occasionally causes clinically serious consequences. Initial management is
      medical; however, in some cases surgery might be required. A premature neonate
      with birth weight of 1370 grams was managed in our ICU. The patient was
      mechanical ventilator dependent due to GER. The patient needed Nissen
      fundoplication for successfully weaning off the ventilator. 

PMID- 25057466
TI  - Aberrant error processing in relation to symptom severity in obsessive-compulsive
      disorder: A multimodal neuroimaging study.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by maladaptive
      repetitive behaviors that persist despite feedback. Using multimodal
      neuroimaging, we tested the hypothesis that this behavioral rigidity reflects
      impaired use of behavioral outcomes (here, errors) to adaptively adjust
      responses. We measured both neural responses to errors and adjustments in the
      subsequent trial to determine whether abnormalities correlate with symptom
      severity. Since error processing depends on communication between the anterior
      and the posterior cingulate cortex, we also examined the integrity of the
      cingulum bundle with diffusion tensor imaging. METHODS: Participants performed
      the same antisaccade task during functional MRI and electroencephalography
      sessions. We measured error-related activation of the anterior cingulate cortex
      (ACC) and the error-related negativity (ERN). We also examined post-error
      adjustments, indexed by changes in activation of the default network in trials
      surrounding errors. RESULTS: OCD patients showed intact error-related ACC
      activation and ERN, but abnormal adjustments in the post- vs. pre-error trial.
      Relative to controls, who responded to errors by deactivating the default
      network, OCD patients showed increased default network activation including in
      the rostral ACC (rACC). Greater rACC activation in the post-error trial
      correlated with more severe compulsions. Patients also showed increased
      fractional anisotropy (FA) in the white matter underlying rACC. CONCLUSIONS:
      Impaired use of behavioral outcomes to adaptively adjust neural responses may
      contribute to symptoms in OCD. The rACC locus of abnormal adjustment and
      relations with symptoms suggests difficulty suppressing emotional responses to
      aversive, unexpected events (e.g., errors). Increased structural connectivity of
      this paralimbic default network region may contribute to this impairment.

PMID- 25057467
TI  - A tensor-based morphometry analysis of regional differences in brain volume in
      relation to prenatal alcohol exposure.
AB  - Reductions in brain volumes represent a neurobiological signature of fetal
      alcohol spectrum disorders (FASD). Less clear is how regional brain tissue
      reductions differ after normalizing for brain size differences linked with FASD
      and whether these profiles can predict the degree of prenatal exposure to
      alcohol. To examine associations of regional brain tissue excesses/deficits with
      degree of prenatal alcohol exposure and diagnosis with and without correction for
      overall brain volume, tensor-based morphometry (TBM) methods were applied to
      structural imaging data from a well-characterized, demographically homogeneous
      sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n =
      16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly
      associated with regionally pervasive brain tissue reductions in: (1) the
      thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum
      and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the
      precuneus and superior parietal lobule. When overall brain size was factored out
      of the analysis on a subject-by-subject basis, no regions showed significant
      associations with alcohol exposure. FASD diagnosis was associated with a similar
      deformation pattern, but few of the regions survived FDR correction. In data
      driven independent component analyses (ICA) regional brain tissue deformations
      successfully distinguished individuals based on extent of prenatal alcohol
      exposure and to a lesser degree, diagnosis. The greater sensitivity of the
      continuous measure of alcohol exposure compared with the categorical diagnosis
      across diverse brain regions underscores the dose dependence of these effects.
      The ICA results illustrate that profiles of brain tissue alterations may be a
      useful indicator of prenatal alcohol exposure when reliable historical data are
      not available and facial features are not apparent. 

PMID- 25057469
TI  - An asymptomatic multiple magnet ingestion with transmesenteric entero-enteric
      fistula.
AB  - Ingestion of foreign bodies is a common presenting complaint in the pediatric
      emergency department. We present a case of a child in whom disc battery ingestion
      was suspected initially. The immobility of the foreign body on few days of
      conservative management raised the suspicion of two magnets. At operation, two
      magnets were found in the bowel causing a transmesenteric entero-enteric fistula.

PMID- 25057470
TI  - Intraluminal gossypiboma.
AB  - Gossypiboma (GP) or retained surgical sponge is one of the rare surgical
      complications which can happen despite precautions. Because of the medico-legal
      issues, it is under-reported. An 8-year-old thalassemic girl, with a history of
      splenectomy and cholecystectomy, presented to us with acute intestinal
      obstruction and required surgical exploration. Intraluminal gossypiboma
      obstructing the ileum was found. Though a rare cause, gossypiboma should also be
      included in the differential diagnoses of postoperative intestinal obstruction. 

PMID- 25057471
TI  - Myofibroepithelial polyp of the ureter.
AB  - Ureteral tumors are rare and benign tumors are even rarer. Most of such tumors
      are diagnosed after nephroureterectomy assuming a malignant lesion, but with
      modern technological advancements like contrast enhanced CT scan or MR urography
      and ureteroscopic biopsy, benign nature of such tumors can be established
      preoperatively with an aim to preserve the renal unit. Here we report a case of
      10-year old boy who presented with chronic right loin pain. DTPA scan showed
      complete loss of function of the right kidney. He was diagnosed to have an
      inflammatory myofibroepithelial polyp of right lower ureter and treated by
      nephroureterectomy. 

PMID- 25057472
TI  - Segmental dilatation of intestine presenting as partial intestinal obstruction in
      a child.
AB  - Segmental dilatation of the intestine in pediatric age group is a rare entity.
      Patients usually present with partial intestinal obstruction which may delay
      surgical decision. Our case was an 18-month-old girl, who presented with partial
      intestinal obstruction, provisionally diagnosed as a case of Hirschsprung's
      disease. Diagnostic evaluation with contrast study gave a clue of small
      intestinal obstruction with a dilated segment. 

PMID- 25057473
TI  - Hypertrophic Pyloric Stenosis developing In a Patient Operated for Patent Urachus
      - A Case Report.
AB  - A neonate with patent urachus (PU) who later developed hypertrophic pyloric
      stenosis (HPS) is being reported. The newborn was first operated for PU; post
      operatively he developed persistent vomiting and radiological workup confirmed
      HPS. Pyloromyotomy was performed with an uneventful recovery. 

PMID- 25057474
TI  - Aspiration cytology diagnosis of lipoblastoma of the back.

PMID- 25057475
TI  - Fecalith causing intestinal obstruction in a patient with seckel syndrome.

PMID- 25057476
TI  - An unusual cause of recurrent chylothorax: gorham syndrome.

PMID- 25057477
TI  - Rhabdomyosarcoma of urinary bladder.

PMID- 25057478
TI  - Regression of cervical cystic hygroma with a single session of sclerotherapy.

PMID- 25057480
TI  - Redox signaling in degenerative diseases: from molecular mechanisms to health
      implications.

PMID- 25057479
TI  - Obsessive-compulsive aspects and pathological gambling in an Italian sample.
AB  - INTRODUCTION: Gambling behaviour appears as repetitive and difficult to resist
      and seems to be aimed at neutralizing or reducing negative feelings such as
      anxiety and tension, confirming its similarities with the obsessive-compulsive
      spectrum. Aims. Estimating the prevalence of gambling behaviour in an Italian
      sample and assessing the effects of sociodemographic variables and the
      correlations between gambling behaviour and obsessive-compulsive features.
      METHODS: A sample of 300 Italian subjects was evaluated based on gambling
      behaviours and obsessive-compulsive attitudes. The assessment was carried out in
      small centers in Italy, mainly in coffee and tobacco shops, where slot machines
      are located, using the South Oaks Gambling Screen (SOGS) and the MOCQ-R, a
      reduced form of Maudsley Obsessional-Compulsive Questionnaire. RESULTS: A
      negative correlation between SOGS and MOPQ-R, with reference to the control and
      cleaning subscales, was evidenced in the majority of the examined subjects. Both
      evaluating instruments showed reliability and a good discriminative capacity.
      CONCLUSIONS: Our study evidenced that the sample of gamblers we analysed did not
      belong to the obsessive-compulsive disorders area, supporting the validity of the
      model proposed by DSM-5 for the classification of PG. These data confirm the
      importance of investing in treatments similar to those used for substance use
      disorders.

PMID- 25057481
TI  - MPINet: metabolite pathway identification via coupling of global metabolite
      network structure and metabolomic profile.
AB  - High-throughput metabolomics technology, such as gas chromatography mass
      spectrometry, allows the analysis of hundreds of metabolites. Understanding that
      these metabolites dominate the study condition from biological pathway
      perspective is still a significant challenge. Pathway identification is an
      invaluable aid to address this issue and, thus, is urgently needed. In this
      study, we developed a network-based metabolite pathway identification method,
      MPINet, which considers the global importance of metabolites and the unique
      character of metabolomic profile. Through integrating the global metabolite
      functional network structure and the character of metabolomic profile, MPINet
      provides a more accurate metabolomic pathway analysis. This integrative strategy
      simultaneously captures the global nonequivalence of metabolites in a pathway and
      the bias from metabolomic experimental technology. We then applied MPINet to four
      different types of metabolite datasets. In the analysis of metastatic prostate
      cancer dataset, we demonstrated the effectiveness of MPINet. With the analysis of
      the two type 2 diabetes datasets, we show that MPINet has the potentiality for
      identifying novel pathways related with disease and is reliable for analyzing
      metabolomic data. Finally, we extensively applied MPINet to identify drug
      sensitivity related pathways. These results suggest MPINet's effectiveness and
      reliability for analyzing metabolomic data across multiple different application
      fields. 

PMID- 25057483
TI  - The human plasma membrane peripherome: visualization and analysis of
      interactions.
AB  - A major part of membrane function is conducted by proteins, both integral and
      peripheral. Peripheral membrane proteins temporarily adhere to biological
      membranes, either to the lipid bilayer or to integral membrane proteins with
      noncovalent interactions. The aim of this study was to construct and analyze the
      interactions of the human plasma membrane peripheral proteins (peripherome
      hereinafter). For this purpose, we collected a dataset of peripheral proteins of
      the human plasma membrane. We also collected a dataset of experimentally verified
      interactions for these proteins. The interaction network created from this
      dataset has been visualized using Cytoscape. We grouped the proteins based on
      their subcellular location and clustered them using the MCL algorithm in order to
      detect functional modules. Moreover, functional and graph theory based analyses
      have been performed to assess biological features of the network. Interaction
      data with drug molecules show that ~10% of peripheral membrane proteins are
      targets for approved drugs, suggesting their potential implications in disease.
      In conclusion, we reveal novel features and properties regarding the protein
      protein interaction network created by peripheral proteins of the human plasma
      membrane. 

PMID- 25057484
TI  - Incidence and predicted risk factors of pressure ulcers in surgical patients:
      experience at a medical center in Taipei, Taiwan.
AB  - PURPOSE: To explore the context of incidence of and associated risk factors for
      pressure ulcers amongst the population of surgical patients. METHODS: The initial
      study cohort was conducted with a total of 297 patients admitted to a teaching
      hospital for a surgical operation from November 14th to 27th 2006 in Taipei,
      Taiwan. The Braden scale, pressure ulcers record sheet, and perioperative patient
      outcomes free from signs and symptoms of injury related to positioning and
      related nursing interventions and activities were collected. RESULTS: The
      incidence of immediate and thirty-minute-later pressure ulcers is 9.8% (29/297)
      and 5.1% (15/297), respectively. Using logistic regression model, the
      statistically significantly associated risk factors related to immediate and
      thirty-minute-later pressure ulcers include operation age, type of anesthesia,
      type of operation position, type of surgery, admission Braden score, and number
      of nursing intervention after adjustment for confounding factors. CONCLUSION:
      Admission Braden score and number of nursing intervention are well-established
      protected factors for the development of pressure ulcers. Our study shows that
      older operation age, type of anesthesia, type of operation position, and type of
      surgery are also associated with the development of pressure ulcers.

PMID- 25057485
TI  - Phytochemicals from Kaempferia angustifolia Rosc. and their cytotoxic and
      antimicrobial activities.
AB  - Phytochemical investigation on rhizomes of Kaempferia angustifolia has afforded a
      new abietene diterpene, kaempfolienol (1) along with crotepoxide (2),
      boesenboxide (3), 2'-hydroxy-4,4',6'-trimethoxychalcone (4), zeylenol (5), 6
      methylzeylenol (6), (24S)-24-methyl-5alpha-lanosta-9(11), 25-dien-3beta-ol (7),
      sucrose, beta-sitosterol, and its glycoside (8). The structures of the compounds
      were elucidated on the basis of spectroscopic methods (IR, MS, and NMR).
      Isolation of 6-methylzeylenol (6), (24S)-24-methyl-5alpha-lanosta-9(11), 25-dien
      3beta-ol (7), and beta-sitosterol-3-O-beta-D-glucopyranoside (8) from this plant
      species has never been reported previously. The spectroscopic data of (7) is
      firstly described in this paper. Cytotoxic screening indicated that most of the
      pure compounds tested showed significant activity with (4) showing the most
      potent activity against HL-60 (human promyelocytic leukemia) and MCF-7 (human
      breast cancer) cell lines. However, all extracts and most of the pure compounds
      tested were found to be inactive against HT-29 (human colon cancer) and HeLa
      (human cervical cancer) cell lines. Similarly, none of the extracts or compounds
      showed activity in the antimicrobial testing. 

PMID- 25057486
TI  - Effect of various acaricides on hatchability of eggs of Rhipicephalus (Boophilus)
      microplus.
AB  - The effect of commonly used acaricides (amitraz, cypermethrin, deltamethrin,
      fenvalerate, and flumethrin) on the eggs of Rhipicephalus (Boophilus) microplus
      collected from Ludhiana, Punjab, was evaluated by egg hatch assay (EHA). The
      regression graph of probit hatchability and per cent inhibition of hatching (IH%)
      of eggs was plotted against log values of concentration of various acaricides.
      All concentrations of flumethrin and amitraz caused complete inhibition of
      hatching, whereas a hatchability of 31.0 +/- 6.1, 40.0 +/- 5.2 and 19.3 +/- 1.7%
      was only recorded at the highest concentration of cypermethrin, deltamethrin, and
      fenvalerate, respectively. An increase in the concentration of the acaricide
      showed a significant effect on the IH% of eggs for cypermethrin (P < 0.01) and
      deltamethrin (P < 0.05) but was nonsignificant for fenvalerate. The slope of the
      regression curve of IH% was utilized for the calculation of the dose of various
      acaricides causing inhibition of hatching for 95% eggs (LC95) and the
      discriminating dose (DD). Results indicated that maximum DD was recorded for
      fenvalerate (2.136%), followed by cypermethrin (0.214%) and deltamethrin
      (0.118%). The results of the current study will be helpful in formulating
      effective control strategies against ticks. 

PMID- 25057487
TI  - Differential expression of osteo-modulatory molecules in periodontal ligament
      stem cells in response to modified titanium surfaces.
AB  - This study assessed differential gene expression of signaling molecules involved
      in osteogenic differentiation of periodontal ligament stem cells (PDLSCs)
      subjected to different titanium (Ti) surface types. PDLSCs were cultured on
      tissue culture polystyrene (TCPS), and four types of Ti discs (PT, SLA,
      hydrophilic PT (pmodPT), and hydrophilic SLA (modSLA)) with no osteoinductive
      factor and then osteogenic activity, including alkaline phosphatase (ALP)
      activity, mRNA expression of runt-related gene 2, osterix, FOSB, FRA1, and
      protein levels of osteopontin and collagen type IA, were examined. The highest
      osteogenic activity appeared in PDLSCs cultured on SLA, compared with the TCPS
      and other Ti surfaces. The role of surface properties in affecting signaling
      molecules to modulate PDLSC behavior was determined by examining the regulation
      of Wnt pathways. mRNA expression of the canonical Wnt signaling molecules, Wnt3a
      and beta-catenin, was higher on SLA and modSLA than on smooth surfaces, but gene
      expression of the calcium-dependent Wnt signaling molecules Wnt5a, calmodulin,
      and NFATc1 was increased significantly on PT and pmodPT. Moreover, integrin
      alpha2/beta1, sonic hedgehog, and Notch signaling molecules were affected
      differently by each surface modification. In conclusion, surface roughness and
      hydrophilicity can affect differential Wnt pathways and signaling molecules,
      targeting the osteogenic differentiation of PDLSCs. 

PMID- 25057489
TI  - Oil palm frond juice as future fermentation substrate: a feasibility study.
AB  - Oil palm frond (OPF) juice is a potential industrial fermentation substrate as it
      has high sugars content and the OPF are readily available daily. However, maximum
      sugars yield and storage stability of the OPF juice are yet to be determined.
      This study was conducted to determine the effect of physical pretreatment and
      storage duration of OPF petiole on sugars yield. Storage stability of OPF juice
      at different storing conditions was also investigated. It was found that OPF
      petiole squeezed by hydraulic pressing machine gave the highest sugars recovery
      at almost 40 g/kg, accounting for a recovery yield of 88%. Storage of OPF petiole
      up to 72 hrs prior to squeezing reduced the free sugars by 11 g/kg. Concentrated
      OPF juice with 95% water removal had the best storage stability at both 4 and 30
      degrees C, when it was stored for 10 days. Moreover, concentrated OPF syrup
      prepared by thermal processing did not give any Maillard effect on microbial
      growth. Based on our results, OPF juice meets all the criteria as a good
      fermentation substrate as it is renewable, consistently available, and easy to be
      obtained, it does not inhibit microbial growth and product formation, and it
      contains no impurities.

PMID- 25057488
TI  - Aronia melanocarpa treatment and antioxidant status in selected tissues in Wistar
      rats.
AB  - Aronia juice is considered to be a source of compounds with high antioxidative
      potential. We conducted a study on the impact of compounds in the Aronia juice on
      oxidative stress in plasma and brain tissues. The influence of Aronia juice on
      oxidative stress parameters was tested with the use of a model with a high
      content of fructose and nonsaturated fats. Therefore, the activity of enzymatic
      (catalase, CAT, and paraoxonase, PON) and nonenzymatic (thiol groups, SH, and
      protein carbonyl groups, PCG) oxidative stress markers, which indicate changes in
      the carbohydrate and protein profiles, was marked in brain tissue homogenates.
      Adding Aronia caused statistically significant increase in the CAT activity in
      plasma in all tested diets, while the PON activity showed a statistically
      significant increase only in case of high fat diet. In animals fed with Aronia
      juice supplemented with carbohydrates or fat, statistically significant increase
      in the PON activity and the decrease in the CAT activity in brain tissue were
      observed. In case of the high fat diet, an increase in the number of SH groups
      and a decrease in the number of PCG groups in brain tissue were observed. 

PMID- 25057490
TI  - Resveratrol ameliorates motor neuron degeneration and improves survival in
      SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
AB  - Resveratrol has recently been used as a supplemental treatment for several
      neurological and nonneurological diseases. It is not known whether resveratrol
      has neuroprotective effect on amyotrophic lateral sclerosis (ALS). To assess the
      effect of resveratrol on the disease, we tested this agent on an ALS model of
      SOD1(G93A) transgenic mouse. Rotarod measurement was performed to measure the
      motor function of the ALS mice. Nissl staining and SMI-32 immunofluorescent
      staining were used to determine motor neurons survival in the spinal cord of the
      ALS mice. Hematoxylin-eosin (H&E), succinic dehydrogenase (SDH), and cytochrome
      oxidase (COX) staining were applied to pathologically analyze the skeletal
      muscles of the ALS mice. We found that resveratrol treatment significantly
      delayed the disease onset and prolonged the lifespan of the ALS mice.
      Furthermore, resveratrol treatment attenuated motor neuron loss, relieved muscle
      atrophy, and improved mitochondrial function of muscle fibers in the ALS mice. In
      addition, we demonstrated that resveratrol exerted these neuroprotective effects
      mainly through increasing the expression of Sirt1, consequently suppressing
      oxidative stress and downregulating p53 and its related apoptotic pathway.
      Collectively, our findings suggest that resveratrol might provide a promising
      therapeutic intervention for ALS. 

PMID- 25057491
TI  - Investigation of peak pressure index parameters for people with spinal cord
      injury using wheelchair tilt-in-space and recline: methodology and preliminary
      report.
AB  - The purpose of this study was to determine the effect of the sensel window's
      location and size when calculating the peak pressure index (PPI) of pressure
      mapping with varying degrees of wheelchair tilt-in-space (tilt) and recline in
      people with spinal cord injury (SCI). Thirteen power wheelchair users were
      recruited into this study. Six combinations of wheelchair tilt (15 degrees , 25
      degrees , and 35 degrees ) and recline (10 degrees  and 30 degrees ) were used by
      the participants in random order. Displacements of peak pressure and center of
      pressure were extracted from the left side of the mapping system. Normalized PPI
      was computed for three sensel window dimensions (3 sensels * 3 sensels, 5 * 5,
      and 7 * 7). At least 3.33 cm of Euclidean displacement of peak pressures was
      observed in the tilt and recline. For every tilt angle, peak pressure
      displacement was not significantly different between 10 degrees  and 30 degrees 
      recline, while center of pressure displacement was significantly different (P <
      .05). For each recline angle, peak pressure displacement was not significantly
      different between pairs of 15 degrees , 25 degrees , and 35 degrees  tilt, while
      center of pressure displacement was significantly different between 15 degrees 
      versus 35 degrees  and 25 degrees  versus 35 degrees . Our study showed that peak
      pressure displacement occurs in response to wheelchair tilt and recline,
      suggesting that the selected sensel window locations used to calculate PPI should
      be adjusted during changes in wheelchair configuration.

PMID- 25057493
TI  - Investigation of cytotoxicity of phosphoryl choline modified single-walled carbon
      nanotubes under a live cell station.
AB  - Single-walled carbon nanotubes (SWCNTs) and various modified SWCNTs have drawn a
      lot of attention due to their potential applications in biomedical field. Before
      further moving on to real clinical applications, hydrophobicity and toxicity of
      SWCNTs should be investigated thoroughly. In this paper, 2-methacryloyloxy ethyl
      phosphorylcholine (MPC) was adopted to modify SWCNTs and phosphoryl choline was
      grafted onto SWCNTs as small molecule moieties and polymeric chains, which made
      SWCNTs dispersed stably both in water and in cell culture medium for a long time.
      Cytotoxicity of pristine and modified SWCNTs were assayed upon successful
      preparation of the designed modified SWCNT. Furthermore, the internalization of
      SWCNTs by three cells was investigated using a live cell station under normal
      culture temperature (37 degrees C) and low temperature (4 degrees C). The results
      showed that the internalization of modified SWCNTs was related to both the active
      transport and the passive transport. Although the modification with phosphoryl
      choline remarkably reduced the cytotoxicity of SWCNTs, the results were probably
      due to other reasons such as the decrease in the ratio of cells which
      internalized modified SWCNTs since the cells without SWCNTs occupation still
      exhibited normal states. 

PMID- 25057492
TI  - Mannosylated chitosan nanoparticles for delivery of antisense oligonucleotides
      for macrophage targeting.
AB  - The therapeutic potential of antisense oligonucleotides (ASODN) is primarily
      dependent upon its safe and efficient delivery to specific cells overcoming
      degradation and maximizing cellular uptake in vivo. The present study focuses on
      designing mannosylated low molecular weight (LMW) chitosan nanoconstructs for
      safe ODNs delivery by macrophage targeting. Mannose groups were coupled with LMW
      chitosan and characterized spectroscopically. Mannosylated chitosan ODN
      nanoparticles (MCHODN NPs) were formulated by self-assembled method using various
      N/P ratio (moles of amine groups of MCH to phosphate moieties of ODNs) and
      characterized for gel retardation assay, physicochemical characteristics,
      cytotoxicity and transfection efficiency, and antisense assay. Complete
      complexation of MCH/ODN was achieved at charge ratio of 1:1 and above. On
      increasing the N/P ratio of MCH/ODN, particle size of the NPs decreased whereas
      zeta potential (ZV) increased. MCHODN NPs displayed much higher transfection
      efficiency into Raw 264.7 cells (bears mannose receptors) than Hela cells and no
      significant toxicity was observed at all MCH concentrations. Antisense assay
      revealed that reduction in lipopolysaccharide (LPS) induced serum TNF-alpha is
      due to antisense activity of TJU-2755 ODN (sequence complementary to 3'-UTR of
      TNF-alpha). These results suggest that MCHODN NPs are acceptable choice to
      improve transfection efficiency in vitro and in vivo. 

PMID- 25057494
TI  - Comparison of commercial genetic-testing services in Korea with 23andMe service.
AB  - INTRODUCTION: Genetic testing services for disease prediction, drug responses,
      and traits are commercially available by several companies in Korea. However,
      there has been no evaluation study for the accuracy and usefulness of these
      services. We aimed to compare two genetic testing services popular in Korea with
      23andMe service in the United States. MATERIALS AND METHODS: We compared the
      results of two persons (one man and one woman) serviced by Hellogene Platinum
      (Theragen Bio Institute), DNAGPS Optimus (DNAlink), and 23andMe service. RESULTS:
      Among 3 services, there were differences in the estimation of relative risks for
      the same disease. For lung cancer, the range of relative risk was from 0.9 to
      2.09. These differences were thought to be due to the differences of applied
      single nucleotide polymorphisms (SNPs) in each service for the calculation of
      risk. Also, the algorithm and population database would have influence on the
      estimation of relative disease risks. The concordance rate of SNP calls between
      DNAGPS Optimus and 23andMe services was 100% (30/30). conclusions: Our study
      showed differences in disease risk estimations among three services, although
      they gave good concordance rate for SNP calls. We realized that the genetic
      services need further evaluation and standardization, especially in disease risk
      estimation algorithm.

PMID- 25057496
TI  - Aberrant frequency of IL-10-producing B cells and its association with Treg/Th17
      in adult primary immune thrombocytopenia patients.
AB  - BACKGROUND: Regulatory B cells (Breg) are a distinct B cell subset with
      immunoregulatory properties. Pivotal to Breg function is interleukin-10. This
      study was to investigate the role of IL-10-producing B cell (B10) and its
      association with Treg and Th17 subsets in immune thrombocytopenia (ITP) patients.
      METHODS: Peripheral blood mononuclear cells from ITP patients and controls were
      stimulated with PMA, ionomycin, and Brefeldin A. The frequencies of CD19(+)IL
      10(+) B cells, CD3(+)CD4(+)IL-17(+) Th17 cells, and CD4(+)CD25(hi)Foxp3(+) Treg
      cells were analyzed by flow cytometry. The mRNA expression of Foxp3 and RORgammat
      was detected by real-time quantitative PCR. RESULTS: The number of B10 cells was
      elevated in ITP patients. After first-line therapies, it remained at high level
      in patients who achieved complete or partial response but decreased in those who
      acquired no response. There was a positive correlation between B10 cells and
      Tregs in ITP both before and after therapies. The ratio of Treg/Th17 decreased in
      ITP, and it strongly correlated with B10 cells. CONCLUSIONS: The frequency of B10
      cells is elevated in ITP and it correlates with both the Tregs counts and the
      Treg/Th17 ratio. B10 cells to regulate functional T cell subsets might be
      impaired in patients with ITP.

PMID- 25057497
TI  - A complete molecular diagnostic procedure for applications in surveillance and
      subtyping of avian influenza virus.
AB  - INTRODUCTION: The following complete molecular diagnostic procedure we developed,
      based on real-time quantitative PCR and traditional PCR, is effective for avian
      influenza surveillance, virus subtyping, and viral genome sequencing. METHOD:
      This study provides a specific and sensitive step-by-step procedure for efficient
      avian influenza identification of 16 hemagglutinin and 9 neuraminidase avian
      influenza subtypes. RESULT AND CONCLUSION: This diagnostic procedure may prove
      exceedingly useful for virological and ecological advancements in global avian
      influenza research.

PMID- 25057495
TI  - The landscape of protein biomarkers proposed for periodontal disease: markers
      with functional meaning.
AB  - Periodontal disease (PD) is characterized by a deregulated inflammatory response
      which fails to resolve, activating bone resorption. The identification of the
      proteomes associated with PD has fuelled biomarker proposals; nevertheless, many
      questions remain. Biomarker selection should favour molecules representing an
      event which occurs throughout the disease progress. The analysis of proteome
      results and the information available for each protein, including its functional
      role, was accomplished using the OralOme database. The integrated analysis of
      this information ascertains if the suggested proteins reflect the cell and/or
      molecular mechanisms underlying the different forms of periodontal disease. The
      evaluation of the proteins present/absent or with very different concentrations
      in the proteome of each disease state was used for the identification of the
      mechanisms shared by different PD variants or specific to such state. The
      information presented is relevant for the adequate design of biomarker panels for
      PD. Furthermore, it will open new perspectives and help envisage future studies
      targeted to unveil the functional role of specific proteins and help clarify the
      deregulation process in the PD inflammatory response. 

PMID- 25057498
TI  - Defining loci in restriction-based reduced representation genomic data from
      nonmodel species: sources of bias and diagnostics for optimal clustering.
AB  - Next generation sequencing holds great promise for applications of
      phylogeography, landscape genetics, and population genomics in wild populations
      of nonmodel species, but the robustness of inferences hinges on careful
      experimental design and effective bioinformatic removal of predictable artifacts.
      Addressing this issue, we use published genomes from a tunicate, stickleback, and
      soybean to illustrate the potential for bioinformatic artifacts and introduce a
      protocol to minimize two sources of error expected from similarity-based de-novo
      clustering of stacked reads: the splitting of alleles into different clusters,
      which creates false homozygosity, and the grouping of paralogs into the same
      cluster, which creates false heterozygosity. We present an empirical application
      focused on Ciona savignyi, a tunicate with very high SNP heterozygosity (~0.05),
      because high diversity challenges the computational efficiency of most existing
      nonmodel pipelines while also potentially exacerbating paralog artifacts. The
      simulated and empirical data illustrate the advantages of using higher sequence
      difference clustering thresholds than is typical and demonstrate the utility of
      our protocol for efficiently identifying an optimum threshold from data without
      prior knowledge of heterozygosity. The empirical Ciona savignyi data also
      highlight null alleles as a potentially large source of false homozygosity in
      restriction-based reduced representation genomic data. 

PMID- 25057499
TI  - Hepatic stellate cell coculture enables sorafenib resistance in Huh7 cells
      through HGF/c-Met/Akt and Jak2/Stat3 pathways.
AB  - PURPOSE: Tumor microenvironment confers drug resistance to kinase inhibitors by
      increasing RKT ligand levels that result in the activation of cell-survival
      signaling including PI3K and MAPK signals. We assessed whether HSC-LX2 coculture
      conferred sorafenib resistance in Huh7 and revealed the mechanism underlying the
      drug resistance. EXPERIMENTAL DESIGN: The effect of LX2 on sorafenib resistance
      was determined by coculture system with Huh7 cells. The rescue function of LX2
      supernatants was assessed by MTT assay and fluorescence microscopy. The
      underlying mechanism was tested by administration of pathway inhibitors and
      manifested by Western blotting. RESULTS: LX2 coculture significantly induced
      sorafenib resistance in Huh7 by activating p-Akt that led to reactivation of p
      ERK. LX2 secreted HGF into the culture medium that triggered drug resistance, and
      exogenous HGF could also induce sorafenib resistance. The inhibition of p-Akt
      blocked sorafenib resistance caused by LX2 coculture. Increased phosphorylation
      of Jak2 and Stat3 was also detected in LX2 cocultured Huh7 cells. The Jak
      inhibitor tofacitinib reversed sorafenib resistance by blocking Jak2 and Stat3
      activation. The combined administration of sorafenib and p-Stat3 inhibitor S3I
      201 augmented induced apoptosis even in the presence of sorafenib resistance.
      CONCLUSIONS: HSC-LX2 coculture induced sorafenib resistance in Huh7 through
      multiple pathways: HGF/c-Met/Akt pathway and Jak2/Stat3 pathway. A combined
      administration of sorafenib and S3I-201 was able to augment sorafenib-induced
      apoptosis even in the presence of LX2 coculture.

PMID- 25057500
TI  - P-selectin: an unpredicted factor for deep vein thrombosis after total hip
      arthroplasty.
AB  - INTRODUCTION: Deep vein thrombosis (DVT) is a severe complication after total hip
      arthroplasty (THA). It leads to acute pulmonary embolism, a life-threatening
      disease. P-selectin is a 140-kDa transmembrane glycoprotein. Elevated P-selectin
      was associated with 1.7-fold increase in the risk of venous thrombosis. MATERIALS
      AND METHODS: To confirm the association, a total of 91 subjects who received
      primary total hip arthroplasty using lateral approach performed by one skilled
      orthopedic surgeon were studied. All the patients were consecutively enrolled at
      the Center of Diagnosis and Treatment for Joint Diseases, Drum Tower Hospital
      affiliated to the Medical School of Nanjing University from 2010 to 2012. All the
      subjects received venography 3-5 days after operation. We measured P-selectin by
      means of a highly sensitive sandwich ELISA technique and a commercially available
      test reagent set. RESULTS: No significant association was detected between P
      selectin and DVT (all P values > 0.05). DeltasP-selectin was correlated with
      weight, APTT after operation, history of DVT, and diagnosis of primary disease (
      P values were 0.03, 0.03, 0.04, and 0.02, resp.). CONCLUSION: P-selectin may not
      be a predicted factor for deep vein thrombosis after total hip arthroplasty.

PMID- 25057501
TI  - Morphometric approach to pulp fibroblast development in tooth germ.
AB  - This paper builds a morphometric framework for the analysis of dental pulp
      fibroblast evolution during tooth development. We investigated 15 tooth germs
      (cases) organized, by histological criteria, in three groups corresponding to
      cap, early bell, and late bell stages, respectively. Each group comprised five
      cases. The morphometric description used the following parameters: area (A),
      perimeter (P)--automatically extracted by a color segmentation technique, and
      form factor (FF)--calculated as 4piA/P (2). The designed framework operated at
      inter- and intragroup levels. The intergroup analysis quantified the differences
      between groups, in the sense of a relative distance (RD) adequately defined by
      mean-value scaling. We showed that the stage of early bell is approximately 5
      times closer to late bell than to cap. The quantification procedure required
      concomitant information about A, P parameters (as P versus A dependences, or FF
      values), whereas the procedure failed for A or P separately used. The intragroup
      analysis quantified the similarity of the cases belonging to the same stage. We
      proved that, unlike the intergroup tests, the individual exploitation of all
      three descriptors A, P, and FF is effective, yielding highly compatible results.
      Within any group, most cases presented RDs less than 10% from the group mean
      value, regardless of the descriptor type.

PMID- 25057502
TI  - Alcohol drinking patterns and differences in alcohol-related harm: a population
      based study of the United States.
AB  - Alcohol use and associated alcohol-related harm (ARH) are a prevalent and
      important public health problem, with alcohol representing about 4% of the global
      burden of disease. A discussion of ARH secondary to alcohol consumption
      necessitates a consideration of the amount of alcohol consumed and the drinking
      pattern. This study examined the association between alcohol drinking patterns
      and self-reported ARH. Pearson chi-square test (chi (2)) and logistic regression
      analyses were used on data from the National Comorbidity Survey Replication (NCS
      R). The NCS-R is a cross-sectional nationally representative sample. Data was
      obtained by face-to-face interviews from 9282 adults aged >= 18 years in the full
      sample, and 5,692 respondents in a subsample of the full sample. Results
      presented as odds ratio (OR) and 95% confidence intervals (95% CI). Alcohol
      drinking patterns (frequency of drinking, and drinks per occasion) were
      associated with increased risks of self-reported ARH; binge or "risky" drinking
      was strongly predictive of ARH than other categories of drinks per occasion or
      frequency of drinking; and men had significantly higher likelihood of ARH in
      relation to frequency of drinking and drinks per occasion. Findings provide
      evidence for public health practitioners to target alcohol prevention strategies
      at the entire population of drinkers.

PMID- 25057503
TI  - Prevalence of catalase (-21 A/T) gene variant in south Indian (Tamil) population.
AB  - Catalase, an endogenous antioxidant enzyme, is responsible for regulating
      reactive species levels. Several epidemiologic studies have suggested that single
      nucleotide polymorphism in catalase gene may be associated with many diseases.
      The genotype of CAT (-21 A/T) point mutation in promoter region of catalase gene
      was determined by polymerase chain based restriction fragment length polymorphism
      analysis in the DNA of 100 healthy volunteers. The frequency of CAT (-21 A/T)
      gene polymorphism AA, AT, and TT genotypes was found to be 7, 23, and 70 percent,
      respectively. The mutant "T" allele frequency was found to be 0.82 among the
      south Indian (Tamil) population. Chi square analysis showed that the study
      population lies within the Hardy-Weinberg equilibrium. The wild type genotype
      (AA) was found to be very low (7%) and the mutant genotype (AT/TT) was found to
      be more prevalent (93%) among the south Indian population. This suggests that the
      high prevalence of mutant genotype may increase the susceptibility to oxidative
      stress associated diseases. 

PMID- 25057504
TI  - Natural killer cell function and dysfunction in hepatitis C virus infection.
AB  - Viruses must continually adapt against dynamic innate and adaptive responses of
      the host immune system to establish chronic infection. Only a small minority
      (~20%) of those exposed to hepatitis C virus (HCV) spontaneously clear infection,
      leaving approximately 200 million people worldwide chronically infected with HCV.
      A number of recent research studies suggest that establishment and maintenance of
      chronic HCV infection involve natural killer (NK) cell dysfunction. This
      relationship is illustrated in vitro by disruption of typical NK cell responses
      including both cell-mediated cytotoxicity and cytokine production. Expression of
      a number of activating NK cell receptors in vivo is also affected in chronic HCV
      infection. Thus, direct in vivo and in vitro evidence of compromised NK function
      in chronic HCV infection in conjunction with significant epidemiological
      associations between the outcome of HCV infection and certain combinations of NK
      cell regulatory receptor and class I human histocompatibility linked antigen
      (HLA) genotypes indicate that NK cells are important in the immune response
      against HCV infection. In this review, we highlight evidence suggesting that
      selective impairment of NK cell activity is related to establishment of chronic
      HCV infection. 

PMID- 25057506
TI  - A combination of extended fuzzy AHP and fuzzy GRA for government E-tendering in
      hybrid fuzzy environment.
AB  - The recent government tendering process being conducted in an electronic way is
      becoming an inevitable affair for numerous governmental agencies to further
      exploit the superiorities of conventional tendering. Thus, developing an
      effective web-based bid evaluation methodology so as to realize an efficient and
      effective government E-tendering (GeT) system is imperative. This paper firstly
      investigates the potentiality of employing fuzzy analytic hierarchy process (AHP)
      along with fuzzy gray relational analysis (GRA) for optimal selection of
      candidate tenderers in GeT process with consideration of a hybrid fuzzy
      environment with incomplete weight information. We proposed a novel hybrid fuzzy
      AHP-GRA (HFAHP-GRA) method that combines an extended fuzzy AHP with a modified
      fuzzy GRA. The extended fuzzy AHP which combines typical AHP with interval AHP is
      proposed to obtain the exact weight information, and the modified fuzzy GRA is
      applied to aggregate different types of evaluation information so as to identify
      the optimal candidate tenderers. Finally, a prototype system is built and
      validated with an illustrative example for GeT to confirm the feasibility of our
      approach. 

PMID- 25057507
TI  - A Legendre tau-spectral method for solving time-fractional heat equation with
      nonlocal conditions.
AB  - We develop the tau-spectral method to solve the time-fractional heat equation (T
      FHE) with nonlocal condition. In order to achieve highly accurate solution of
      this problem, the operational matrix of fractional integration (described in the
      Riemann-Liouville sense) for shifted Legendre polynomials is investigated in
      conjunction with tau-spectral scheme and the Legendre operational polynomials are
      used as the base function. The main advantage in using the presented scheme is
      that it converts the T-FHE with nonlocal condition to a system of algebraic
      equations that simplifies the problem. For demonstrating the validity and
      applicability of the developed spectral scheme, two numerical examples are
      presented. The logarithmic graphs of the maximum absolute errors is presented to
      achieve the exponential convergence of the proposed method. Comparing between our
      spectral method and other methods ensures that our method is more accurate than
      those solved similar problem. 

PMID- 25057508
TI  - Fault detection of aircraft system with random forest algorithm and similarity
      measure.
AB  - Research on fault detection algorithm was developed with the similarity measure
      and random forest algorithm. The organized algorithm was applied to unmanned
      aircraft vehicle (UAV) that was readied by us. Similarity measure was designed by
      the help of distance information, and its usefulness was also verified by proof.
      Fault decision was carried out by calculation of weighted similarity measure.
      Twelve available coefficients among healthy and faulty status data group were
      used to determine the decision. Similarity measure weighting was done and
      obtained through random forest algorithm (RFA); RF provides data priority. In
      order to get a fast response of decision, a limited number of coefficients was
      also considered. Relation of detection rate and amount of feature data were
      analyzed and illustrated. By repeated trial of similarity calculation, useful
      data amount was obtained. 

PMID- 25057509
TI  - Adaptive broadcasting mechanism for bandwidth allocation in mobile services.
AB  - This paper proposes a tree-based adaptive broadcasting (TAB) algorithm for data
      dissemination to improve data access efficiency. The proposed TAB algorithm first
      constructs a broadcast tree to determine the broadcast frequency of each data and
      splits the broadcast tree into some broadcast wood to generate the broadcast
      program. In addition, this paper develops an analytical model to derive the mean
      access latency of the generated broadcast program. In light of the derived
      results, both the index channel's bandwidth and the data channel's bandwidth can
      be optimally allocated to maximize bandwidth utilization. This paper presents
      experiments to help evaluate the effectiveness of the proposed strategy. From the
      experimental results, it can be seen that the proposed mechanism is feasible in
      practice. 

PMID- 25057505
TI  - Targeting TLR2 for vaccine development.
AB  - Novel and more effective immunization strategies against many animal diseases may
      profit from the current knowledge on the modulation of specific immunity through
      stimulation of innate immune receptors. Toll-like receptor (TLR)2-targeting
      formulations, such as synthetic lipopeptides and antigens expressed in fusion
      with lipoproteins, have been shown to have built-in adjuvant properties and to be
      effective at inducing cellular and humoral immune mechanisms in different animal
      species. However, contradictory data has arisen concerning the profile of the
      immune response elicited. The benefits of targeting TLR2 for vaccine development
      are thus still debatable and more studies are needed to rationally explore its
      characteristics. Here, we resume the main features of TLR2 and TLR2-induced
      immune responses, focusing on what has been reported for veterinary animals. 

PMID- 25057510
TI  - Similarity measure learning in closed-form solution for image classification.
AB  - Adopting a measure is essential in many multimedia applications. Recently,
      distance learning is becoming an active research problem. In fact, the distance
      is the natural measure for dissimilarity. Generally, a pairwise relationship
      between two objects in learning tasks includes two aspects: similarity and
      dissimilarity. The similarity measure provides different information for pairwise
      relationships. However, similarity learning has been paid less attention in
      learning problems. In this work, firstly, we propose a general framework for
      similarity measure learning (SML). Additionally, we define a generalized type of
      correlation as a similarity measure. By a set of parameters, generalized
      correlation provides flexibility for learning tasks. Based on this similarity
      measure, we present a specific algorithm under the SML framework, called
      correlation similarity measure learning (CSML), to learn a parameterized
      similarity measure over input space. A nonlinear extension version of CSML,
      kernel CSML, is also proposed. Particularly, we give a closed-form solution
      avoiding iterative search for a local optimal solution in the high-dimensional
      space as the previous work did. Finally, classification experiments have been
      performed on face databases and a handwritten digits database to demonstrate the
      efficiency and reliability of CSML and KCSML. 

PMID- 25057511
TI  - Simulation analysis of air flow and turbulence statistics in a rib grit roughened
      duct.
AB  - The implementation of variable artificial roughness patterns on a surface is an
      effective technique to enhance the rate of heat transfer to fluid flow in the
      ducts of solar air heaters. Different geometries of roughness elements
      investigated have demonstrated the pivotal role that vortices and associated
      turbulence have on the heat transfer characteristics of solar air heater ducts by
      increasing the convective heat transfer coefficient. In this paper we investigate
      the two-dimensional, turbulent, unsteady flow around rectangular ribs of variable
      aspect ratios by directly solving the transient Navier-Stokes and continuity
      equations using the finite elements method. Flow characteristics and several
      aspects of turbulent flow are presented and discussed including velocity
      components and statistics of turbulence. The results reveal the impact that
      different rib lengths have on the computed mean quantities and turbulence
      statistics of the flow. The computed turbulence parameters show a clear tendency
      to diminish downstream with increasing rib length. Furthermore, the applied
      numerical method is capable of capturing small-scale flow structures resulting
      from the direct solution of Navier-Stokes and continuity equations. 

PMID- 25057512
TI  - A dip-stick type biosensor using bioluminescent bacteria encapsulated in color
      coded alginate microbeads for detection of water toxicity.
AB  - The use of genetically engineered bioluminescent bacteria, in which
      bioluminescence is induced by different modes of toxic action, represents an
      alternative to acute toxicity tests using living aquatic organisms (plants,
      vertebrates, or invertebrates) in an aqueous environment. A number of these
      bacterial strains have been developed, but there have been no attempts to develop
      a hand-held type of biosensor for monitoring or identification of toxicity. We
      report a facile dip-stick type biosensor using genetically engineered
      bioluminescent bacteria as a new platform for classification and identification
      of toxicity in water environments. This dip-stick type biosensor is composed of
      eight different optically color-coded functional alginate beads that each
      encapsulates a different bioluminescent bacterial strain and its corresponding
      fluorescent microbead. These color-coded microbeads exhibit easy identification
      of encapsulated microbeads, since each microbead has a different color code
      depending on the bioluminescent bacterial strain contained and improved cell
      stability compared to liquid culture. This dip-stick type biosensor can
      discriminate different modes of toxic actions (i.e. DNA damage, oxidative damage,
      cell-membrane damage, or protein damage) of sample water tested by simply dipping
      the stick into the water samples. It was found that each color-coded microbead
      emitted distinct bioluminescence, and each dip-stick type biosensor showed
      different bioluminescence patterns within 2 hours, depending on the toxic
      chemicals contained in LB medium, tap water, or river water samples. This dip
      stick type biosensor can, therefore, be widely and practically used in checking
      toxicity of water in the environment primarily in situ, possibly indicating the
      status of biodiversity. 

PMID- 25057513
TI  - Layered MnO2 nanosheet as a label-free nanoplatform for rapid detection of
      mercury(II).
AB  - A layered MnO2 nanosheet was established as a label-free fluorescent sensing
      platform for a rapid, sensitive and low-cost detection of mercury(II) ion in
      aqueous solution based on the target-induced conformational change of mercury
      specific oligonucleotide (MSO) and the interactions between the fluorogenic MSO
      probe and MnO2 nanosheet.

PMID- 25057514
TI  - Food safety control of zeranol through voltammetric immunosensing on Au-Pt
      bimetallic nanoparticle surfaces.
AB  - This study reports an accurate and sensitive strategy for zeranol (ZER)
      determination in bovine urine samples. ZER is a mycotoxin widely used as a
      synthetic growth promoter in the livestock production whose residues could
      present a potential risk for human health. Therefore, its use as an animal feed
      additive has been banned in most countries. ZER determination was accomplished
      using an electrochemical system in which bimetallic Au-Pt nanoparticles (Au
      PtNPs) were electro-synthesized on a screen-printed carbon electrode (SPCE). The
      obtained Au-PtNP platform was immunofunctionalized using specific anti-ZER
      antibodies as a strategy to avoid potential interference. After biorecognition,
      ZER was directly oxidized and detected by square-wave voltammetry (SWV). The Au
      PtNP surface was characterized by scanning electron microscopy (SEM), X-ray
      diffraction (XRD) and cyclic voltammetry (CV). The limit of detection calculated
      was 0.01 ng mL(-1) with a wide linear range from 0.03 to 30 ng mL(-1). This
      method promises to be suitable for ZER quantification in bovine urine samples
      ensuring food quality and safety, as well as consumer's health. 

PMID- 25057516
TI  - The success of South-eastern Europe Health Network (SEEHN) initiative on
      improvement of the kidney transplant program--facts about Macedonia.

PMID- 25057515
TI  - A sensitive dual colorimetric and fluorescence system for assaying the activity
      of alkaline phosphatase that relies on pyrophosphate inhibition of the peroxidase
      activity of copper ions.
AB  - A novel and highly sensitive colorimetric and fluorescence assay for the accurate
      determination of alkaline phosphatase (ALP) activity has been developed. The
      assay takes advantage of the inhibition of the peroxidase activity of Cu(2+) ions
      caused by complexation with pyrophosphate (PPi), a natural substrate for ALP.
      This inhibition disappears when PPi undergoes ALP catalyzed hydrolysis to
      generate phosphate, which does not bind to Cu(2+) ions. Thus, ALP causes
      generation of uncomplexed Cu(2+) ions, which promote multiple oxidation reactions
      of Amplex UltraRed in the presence of hydrogen peroxide in conjunction with the
      production of intense fluorescence and colorimetric signals. By employing the
      fluorescence and colorimetric assay strategies, ALP can be detected at respective
      concentrations as low as 4.3 pM and 5.4 pM, detection limits that are much lower
      than those associated with previously described methods. The practical diagnostic
      capability of the assay system has been demonstrated by its use to detect ALP in
      human blood serum. 

PMID- 25057517
TI  - Retraction to: Characterization of a novel Cotesia vestalis polydnavirus (CvBV)
      gene containing a ser-rich motif expressed in Plutella xylostella larvae.

PMID- 25057518
TI  - John Hunter: early association of Type A behavior with cardiac mortality.
AB  - Free-floating (easily aroused) hostility is a cardinal symptom of the type A
      behavior pattern, the first psychosocial factor scientifically linked to coronary
      artery disease (CAD). Anger and hostility are associated with the onset and
      outcome of CAD, triggering of myocardial infarction, and lowering the threshold
      to ventricular arrhythmia, all increasing the risk of sudden cardiac death. The
      life of the legendary eighteenth century English surgeon John Hunter is
      illustrative of the type A behavior pattern. His demise and that of a
      contemporary surgeon provide important lessons for the management of anger in
      contemporary society.

PMID- 25057519
TI  - Flow diagnostics essential code: a simple and brief format for the summary of
      leukemia phenotyping.
AB  - BACKGROUND: Flow cytometry is a valuable part in the routine diagnostics of acute
      leukemia (AL). Although internationally recognized definitions of main AL subsets
      are available, there is currently no consensus format for the short summary of
      clinical flow cytometry reports. Since clinical reports are too long for most
      database purposes, there is a need for a standardized format of their short
      summaries. METHODS: The Associazione Italiana Ematologia Oncologia Pediatrica-
      Berlin Frankfurt Muenster (AIEOP-BFM) Flow Network that encompasses reference
      diagnostics laboratories in Australia, Austria, Czechia, Germany, Israel, Italy,
      and Switzerland have designed a pro-forma for the summary of flow cytometry
      results in the diagnosis of leukemia. The process involved several meetings and
      other communications, during which the group established a consensus on the
      essentials that lead to the diagnostic conclusions in childhood AL. RESULTS: The
      "Flow Diagnostics Essential (FDE) Code" is a result from an agreement within the
      AIEOP-BFM Flow Network. In a standardized format, it reports the extent of the
      infiltration by a malignant clone, followed by description antigen expression as
      strong, weak or negative, and a diagnostic conclusion. CONCLUSIONS: A consensus
      brief format (the "FDE Code") has been designed as a brief summary of the
      diagnostic immunophenotype of childhood AL. It is also applicable for the
      diagnostic investigation of other malignancies by flow cytometry. The FDE code
      may be included in the final clinical report and/or used in the setting of a
      multicenter clinical trial database.

PMID- 25057520
TI  - Subcutaneous connective tissue reactions to iRoot SP, mineral trioxide aggregate
      (MTA) Fillapex, DiaRoot BioAggregate and MTA.
AB  - AIM: To evaluate connective tissue reactions to iRoot SP (Innovative Bioceramics,
      Vancouver, BC, Canada), mineral trioxide aggregate (MTA) Fillapex (FLPX) (Angelus
      Solucoes Odontologicas, Londrina, Brazil), DiaRoot Bioaggregate (DiaDent Group
      International, Burnaby, BC, Canada) and white MTA (Angelus, Londrina, Brazil) in
      Wistar rats. METHODOLOGY: A total of 128 dentine tubes filled with the materials
      and 32 empty tubes (control) were implanted into 32 rats. After 7, 15, 30 and 90
      days (n = 8 per period), the animals were euthanized, and the tissues were
      processed for histological evaluation using haematoxylin-eosin (H&E) and Von
      Kossa (VK) staining. Observations were made for cellular inflammatory components
      and the presence of multinucleated giant cells (MNGC), macrophages and tissue
      necrosis. Data were analysed by Fisher's exact and Kruskal-Wallis tests (P <
      0.05). RESULTS: In all experimental periods, MTA FLPX and iRoot SP scored higher
      than the other groups for the variable macrophages (P < 0.05). After 30- and 90
      day experimental periods, MTA FLPX scored higher than the other groups for the
      variable MNGC (P < 0.05). After 90 days, the only group that exhibited samples
      with severe inflammatory response was MTA FLPX. VK positivity was observed in
      areas of necrosis in all groups, except in the control group. CONCLUSIONS: The
      materials were considered biologically acceptable except MTA FLPX, which remained
      toxic to subcutaneous tissue even after 90 days.

PMID- 25057521
TI  - [Definition of criteria for high disease activity using the Juvenile Rheumatoid
      Arthritis Disease Activity Score].

PMID- 25057522
TI  - [Effectiveness of interleukin-1 inhibiton for mevalonate kinase deficiency].

PMID- 25057523
TI  - [Development of consensus treatment plans for juvenile localized scleroderma].

PMID- 25057524
TI  - Bovine embryo survival under oxidative-stress conditions is associated with
      activity of the NRF2-mediated oxidative-stress-response pathway.
AB  - In present study, we sought to examine the ability of preimplantation bovine
      embryos to activate the NF-E2-related factor 2 (NRF2)-mediated oxidative-stress
      response under an oxidative stress environment. In vitro 2-, 4-, 8-, 16-cell-,
      and blastocyst-stage embryos were cultured under low (5%) or high (20%) oxygen
      levels. The expression of NRF2, KEAP1 (NRF2 inhibitor), antioxidants downstream
      of NRF2, and genes associated with embryo metabolism were analyzed between the
      embryo groups using real-time quantitative PCR. NRF2 and KEAP1 protein abundance,
      mitochondrial activity, and accumulation of reactive oxygen species (ROS) were
      also investigated in blastocysts of varying competence that were derived from
      high- or low-oxygen levels. The expression levels of NRF2 and its downstream
      antioxidant genes were higher in 8-cell, 16-cell, and blastocyst stages under
      high oxygen tension, whereas KEAP1 expression was down-regulated under the same
      conditions. Higher expression of NRF2 and lower ROS levels were detected in early
      (competent) blastocysts compared to their late (noncompetent) counterparts in
      both oxygen-tension groups. Similarly, higher levels of active nuclear NRF2
      protein were detected in competent blastocysts compared to their noncompetent
      counterparts. Thus, the survival and developmental competence of embryos cultured
      under oxidative stress are associated with activity of the NRF2-mediated
      oxidative stress response pathway during bovine pre-implantation embryo
      development.

PMID- 25057525
TI  - Comparative analysis of suicide, accidental, and undetermined cause of death
      classification.
AB  - Suicide determination is not standardized across medical examiners, and many
      suspected suicides are later classified as accidental or undetermined. The
      present study investigated patterns between these three groups using a medical
      examiner database and 633 structured interviews with next of kin. There were
      similarities across all three classification groups, including rates of mental
      illness and psychiatric symptoms. Those classified suicide were more likely to be
      male, to have died in a violent fashion, and have a stronger family history of
      suicide. Chronic pain was very common across all three groups, but significantly
      higher in the accidental and undetermined groups.

PMID- 25057527
TI  - Retraction notice to "Simultaneous presence of mucous membrane pemphigoid and
      pemphigus vulgaris: molecular characterization of both autoantibodies" [Clin.
      Immunol. 100 (2001) 219-27].

PMID- 25057526
TI  - Preface.

PMID- 25057529
TI  - Largest U.S. publicly traded medical device and diagnostic companies.

PMID- 25057528
TI  - Reply: To PMID 24369689.

PMID- 25057530
TI  - Largest healthcare executive search firms.

PMID- 25057531
TI  - Top business graduate schools for physician-executives.

PMID- 25057739
TI  - Some suggestions for reviewers and for authors to know what reviewers may be
      looking for.

PMID- 25057741
TI  - Legionella pneumophila serogroup 1 septic arthritis with probable endocarditis in
      an immunodeficient patient.

PMID- 25057742
TI  - Assessing household natural disaster preparedness in Shiraz, Iran, 2011: results
      of a knowledge, attitude, and practices survey.
AB  - OBJECTIVE: Public education and training that focus on appropriate knowledge,
      attitudes, and practices have had a crucial role in preparedness. The aim of this
      study was to assess knowledge, attitudes, and practices of households regarding
      natural disasters in Shiraz, Iran. METHODS: In this cross-sectional descriptive
      study, we used a stratified random sampling technique. The data collection tool
      was a self-administered questionnaire, which was completed in through face-to
      face interviews. The data were analyzed with the SPSS statistical software
      package (version 16). RESULTS: The overall mean scores were 7.3+/-2.0 for
      knowledge, 26.3+/-6.5 for attitudes, and 5.2+/-2.2 for practices. Mean scores for
      all 3 factors were higher in women and married participants. In other
      comparisons, the differences were statistically significant only for the
      associations between gender and the score for practices. The mean knowledge score
      was lower in illiterate participants than in other categories of educational
      status. CONCLUSION: Our findings showed that the knowledge of households
      regarding disaster preparedness was encouraging, but that of attitudes and
      practices might be improved through a greater focus on motivational educational
      programs and cooperation among the organizations involved in public awareness.

PMID- 25057743
TI  - The evolution of breast implants.
AB  - Breast augmentation remains one of the most common aesthetic procedures performed
      in the United States. Silicone implants have undergone an evolution with the
      availability of both fourth- and fifth-generation devices from the 3 leading
      manufacturers in the United States. This article explores the evolution of breast
      implants with special emphasis on the advancement of the silicone implants.
      Clinicians should strive to provide ongoing data and sound science to continue to
      improve clinical outcomes in the future.

PMID- 25057744
TI  - Algorithm and techniques for using Sientra's silicone gel shaped implants in
      primary and revision breast augmentation.
AB  - With the 2006 Food and Drug Administration approval of round silicone gel breast
      implants in the United States, there still remained a lack of versatility in
      implant options. The approval of Sientra's shaped cohesive implants in 2012
      brought with it the innovations needed to address varying patient needs. Because
      access to shaped devices is still fairly recent in the United States, some
      surgeons remain uncomfortable with implementing shaped cohesive gel implants into
      their practice. The author outlines surgical techniques and algorithms from
      experience with the Sientra shaped device, covering the preoperative stage,
      measurements (base diameter, sternal notch to nipple, tissue pinch, and nipple to
      inframammary fold), ideal first candidates, operative techniques, and
      complication avoidance, as well as important factors for shaped-implant
      selection, including chest base diameter, implant height, implant volume, and
      implant projection for the patient's desired outcome. With experience, surgeons
      will find new utility with shaped implants for a variety of patients in their
      practices.

PMID- 25057745
TI  - The Sientra Shaped and Round Cohesive Gel Implants supplement.

PMID- 25057746
TI  - Algorithm and techniques for using Sientra's highly cohesive shaped silicone gel
      implants in primary and revision breast reconstruction.
AB  - BACKGROUND: With the recent availability of shaped silicone gel implants for
      breast reconstruction, many plastic surgeons are inquiring as to when and how
      these devices should be used. Questions about indications, algorithms, and
      techniques have become prevalent. This article reviews the author's experience
      using Sientra's highly cohesive shaped silicone gel devices for breast
      reconstruction. METHODS: A total of 31 patients had prosthetic breast
      reconstruction procedures using Sientra's shaped silicone gel implants. Bilateral
      reconstruction was performed in 16 women; thus, a total of 47 breasts were
      reconstructed or revised. Sientra's 3 shaped implants included the classic-base,
      round-base, and oval-base devices. Reconstructions occurred immediately following
      mastectomy, on a delayed basis following mastectomy, and for revisional purposes
      following a previous reconstruction using a nonshaped device. Mean follow-up for
      the 31 patients was 7.9 months. RESULTS: There were a total of 3 complications
      that occurred in 3 patients (9.6%) and in 3 breasts (6.4%). These included an
      infection in 2 breasts (4.3%) and device exposure due to incisional dehiscence in
      1 breast (2.1%). No patient developed a grade 3 or 4 capsular contracture,
      seroma, or device malposition/rotation. Reoperation was necessary in 3 of 31
      women (9.7%). CONCLUSIONS: Sientra's highly cohesive shaped silicone gel breast
      implant has been useful for controlling breast shape, contour, and position for
      breast reconstruction or revision following mastectomy. Breast projection has
      been maintained, and malrotation has not been observed within the follow-up
      period. Adverse events have been few, and patients have been pleased with the
      surgical outcomes.

PMID- 25057747
TI  - Sientra portfolio of Silimed brand shaped implants with high-strength silicone
      gel: a 5-year primary augmentation clinical study experience and a postapproval
      experience-results from a single-surgeon 108-patient series.
AB  - BACKGROUND: The Sientra portfolio of silicone gel breast implants was approved by
      the Food and Drug Administration on March 9, 2012, and included the first
      approved shaped implants in the United States. The 5-year results from Sientra's
      Core Gel and Continued Access Study and the results of a single surgeon are
      presented. METHODS: This analysis used the data of 640 shaped implants in 321
      primary augmentation patients implanted by 16 study surgeons through 5 years. The
      Kaplan-Meier method was used to analyze safety endpoints. In addition, analysis
      is presented for a single surgeon's results of 213 shaped implants in 108
      postapproval patients through up to 16 months of follow-up (9-month mean) using a
      separate frequency analysis. RESULTS: The overall risk of rupture for primary
      augmentation patients through 5 years was 0.4%, the risk of infection was 1.4%,
      and the risk of capsular contracture (Baker grade III/IV) was 3.9%. Reported
      surgeon satisfaction was 100%, and patient satisfaction remained high. In the
      separate single-surgeon analysis, after 16 months, 4 of the 108 patients
      experienced a complication (3.7%) and 3 underwent a reoperation (2.8%).
      Complications included infection, ptosis (0.9%, each), and capsular contracture
      (1.9%). CONCLUSIONS: The results of Sientra's large clinical study and the
      postapproval data from a single surgeon demonstrate the safety and effectiveness
      of Sientra's shaped implants. The review of the data and author's experience
      illustrate the ease of incorporating shaped implants into any surgical practice.

PMID- 25057749
TI  - Silicone gel breast implants: science and testing.
AB  - BACKGROUND: Since the first generation of breast implants, major design
      innovations, including consistency of the gel, palpability and thickness of the
      shell, and barrier materials in the shell, have been introduced. Surgeons have
      not had metrics to assess and compare available implants. METHODS: Research at
      independent laboratories included 4 tests: gel elasticity (the gel's ability to
      retain its shape), gel compression fracture (the resistance to permanent gel
      deformation), gel-shell peel (the integration of the gel with shell as a cohesive
      unit), and morphological analysis. RESULTS: Sientra's round High-Strength
      Cohesive (HSC) experienced the least gel elasticity (5.805 mm), whereas
      Allergan's round implants experienced the most (7.465 mm). Among shaped implants,
      Allergan 410 experienced the least gel elasticity (3.242 mm), whereas the Sientra
      HSC+ implant experienced the most (4.270 mm). Sientra's round (36.32 lbf) and
      shaped (44.16 lbf) implants demonstrated the highest resistance to gel fracture,
      with Allergan's implants demonstrating the least among round (23.06 lbf) implants
      and Mentor Contour Profile Gel (CPG) among shaped (30.45 lbf) implants. For the
      gel-shell peel test, Sientra's implant required over 26% greater force than
      Allergan's implant and over 35% greater force than Mentor's implant. Sientra's
      shaped implants required more than double the peel force than Allergan 410 (119%
      greater) and Mentor CPG (130% greater). Morphological results showed Sientra's
      implants preserved structural integrity (-1.10% change). CONCLUSIONS: The initial
      findings show that these implant characteristics are individual factors to be
      considered separately and are not necessarily correlative. Further study of
      implants using these and other testing techniques will help clinicians choose
      between implants.

PMID- 25057750
TI  - Preface to the Sientra Shaped and Round Cohesive Gel Implants supplement.

PMID- 25057751
TI  - Evolving practices in augmentation operative technique with Sientra HSC round
      implants.
AB  - As of 2012, breast augmentation surgery continues to be the most commonly
      performed aesthetic surgical procedure in the United States. Surgeons consider a
      multitude of factors when choosing the type and style of breast implant for a
      patient. With the continuous evolution of breast implant designs, there are a
      variety of breast implant options for plastic surgeons to choose from; however,
      round implants remain the implant of choice for breast augmentation. This article
      discusses preoperative planning, implant selection, surgical techniques, and
      postoperative management using Sientra's Silimed brand smooth and textured round
      implants.

PMID- 25057752
TI  - The ecosystem of plastic surgery: a specialty and industry perspective.
AB  - Plastic surgery, a defined surgical specialty, can be viewed as an ecosystem
      facing perturbatory forces, both internal and external, that will disrupt healthy
      checks and balances. This is an evolving system which will adapt to these
      disturbances and evolve as will a natural ecosystem. Returning to the beginning
      of the plastic surgery ecosystem, dating to World War I, identification of the
      challenges and forces within the ecosystem will raise awareness in the plastic
      surgery community. A graphic representation of the ecosystem is offered to
      represent the description and challenges offered to the plastic surgery
      ecosystem. Will this ecosystem return to balance or be radically altered and bear
      little resemblance to the past?

PMID- 25057753
TI  - The biology and evolution of cohesive gel and shaped implants.
AB  - The introduction of the silicone gel implant in 1962 began the modern era of
      breast augmentation, and over the past 50 years, breast implants have evolved to
      encompass a wide array of commercially available implants today. In April 1992,
      the moratorium on silicone gel breast implants began, and much of the experience
      and development of the cohesive shaped implants occurred outside the United
      States. During this time, saline implants were used almost exclusively in North
      America, whereas silicone implants continued to be used throughout the rest of
      the world. In 2001, cohesive gel implants became available in the United States
      under an Investigational Device Exemption Study. Three companies have US Food and
      Drug Administration approval of fifth-generation implants: Sientra, Allergan, and
      Mentor. These implants are unique due to the texture of the shell, implant
      dimensions, gel-shell interaction, gel fill ratio, degree of cross-linking, and
      form stability. Although form stability is a relative term, it may best be
      reserved to describe the increased ability of the implant to maintain its basic,
      intended shape. The cross-linking, form stability, and cohesiveness of these
      fifth-generation implants provide surgeons with an innovative tool to more
      closely create a natural breast in both shape and softness.

PMID- 25057754
TI  - Tuning of surface wettability of RGO-based aerogels for various adsorbates in
      water using different amino acids.
AB  - RGO-based aerogels with varied and controllable surface wettability were
      fabricated using different amino acids. Hydrophobic cys-RGO aerogels prepared by
      L-cysteine exhibited an outstanding adsorption toward oils and organic solvents,
      while hydrophilic lys-RGO aerogels obtained from L-lysine can be used as
      adsorbents for heavy metal ions in water.

PMID- 25057755
TI  - A three-component reaction by photoinduced electron transfer mechanism with N
      protected pyrroles as neutral carbon nucleophiles.
AB  - A new photoinduced three-component reaction between a cyanoarene, an alkene and
      an N-protected pyrrole has been developed. This reaction extended the scope of
      the photo-NOCAS reaction by introducing pyrrole as a neutral carbon-centered
      nucleophile. The cyanoarenes used include tetracyanobenzene (TCB), 2,3,5,6
      tetrafluoro-1,4-dicyanobenzene (TFDCB) and 1,4-dicyanobenzene (DCB). N-Methyl, N
      phenyl and N-Boc pyrroles are suitable nucleophiles in the reaction. Taking
      advantage of the strong electron acceptor ability of the singlet excited TCB, a
      wide range of alkenes, including the highly electron deficient 4-fluoro-, 4
      chloro-, 2,3,4,5,6-pentafluorostyrenes and N-methylmaleimide take part in this
      reaction, leading to the simultaneous 1,2-diarylation of the alkene and the
      regioselective 2-alkylation of the pyrrole ring via sequential formation of two
      new C-C bonds between the three reactants. 

PMID- 25057756
TI  - Rare earth-modified kaolin/NaY-supported Pd-Pt bimetallic catalyst for the
      catalytic combustion of benzene.
AB  - A new type of porous kaolin/NaY composite (KL-NY) with a large specific surface
      area and large pore sizes was synthesized through a one-step crystallization
      process, and rare earth-modified KL-NY-supported Pd-Pt catalysts were studied for
      benzene combustion. The results indicated that the pore volume and specific
      surface area of KL-NY after calcination and crystallization were 0.298 cm(3)/g
      and 365 m(2)/g, respectively, exhibiting appropriate pore structure and good
      thermal stability. Catalysts with rare earth metals greatly enhanced the activity
      of Pd/KL-NY, and the addition of Pt and Ce into the Pd catalyst improved the
      catalytic activity as well as the stability. The catalyst with an optimal Ce
      content and Pt/Pd molar ratio (0.2%Pd-Pt (6:1)/6%Ce/KL-NY) demonstrated the best
      activity for the complete oxidation of benzene at 230  degrees C, and the
      catalyst above maintained the 100% benzene conversion for 960 h. 

PMID- 25057757
TI  - International system of units traceable results of Hg mass concentration at
      saturation in air from a newly developed measurement procedure.
AB  - Data most commonly used at present to calibrate measurements of mercury vapor
      concentrations in air come from a relationship known as the "Dumarey equation".
      It uses a fitting relationship to experimental results obtained nearly 30 years
      ago. The way these results relate to the international system of units (SI) is
      not known. This has caused difficulties for the specification and enforcement of
      limit values for mercury concentrations in air and in emissions to air as part of
      national or international legislation. Furthermore, there is a significant
      discrepancy (around 7% at room temperature) between the Dumarey data and data
      calculated from results of mercury vapor pressure measurements in the presence of
      only liquid mercury. As an attempt to solve some of these problems, a new
      measurement procedure is described for SI traceable results of gaseous Hg
      concentrations at saturation in milliliter samples of air. The aim was to propose
      a scheme as immune as possible to analytical biases. It was based on isotope
      dilution (ID) in the liquid phase with the (202)Hg enriched certified reference
      material ERM-AE640 and measurements of the mercury isotope ratios in ID blends,
      subsequent to a cold vapor generation step, by inductively coupled plasma mass
      spectrometry. The process developed involved a combination of interconnected
      valves and syringes operated by computer controlled pumps and ensured continuity
      under closed circuit conditions from the air sampling stage onward. Quantitative
      trapping of the gaseous mercury in the liquid phase was achieved with 11.5 MUM
      KMnO4 in 2% HNO3. Mass concentrations at saturation found from five measurements
      under room temperature conditions were significantly higher (5.8% on average)
      than data calculated from the Dumarey equation, but in agreement (-1.2% lower on
      average) with data based on mercury vapor pressure measurement results. Relative
      expanded combined uncertainties were estimated following a model based approach.
      They ranged from 2.2% to 2.8% (k = 2). The volume of air samples was traceable to
      the kilogram via weighing of water for the calibration of the sampling syringe.
      Procedural blanks represented on average less than 0.1% of the mass of Hg present
      in 7.4 cm(3) of air, and correcting for these blanks was not an important source
      of uncertainty. 

PMID- 25057758
TI  - VP2, VP7, and NS1 proteins of bluetongue virus targeted in avian reovirus muNS-Mi
      microspheres elicit a protective immune response in IFNAR(-/-) mice.
AB  - Vaccination is critical for controlling the spread of bluetongue virus (BTV). The
      inactivated BTV vaccines that are now being used in Europe are effective in
      preventing outbreaks of BTV but secondary effects associated to repetitive
      inoculation of aluminum-containing adjuvants and the need to develop safer, cross
      reactive, and more efficacious vaccines with differential diagnostic capability
      have re-stimulated the interest in developing improved vaccination strategies
      against BTV. We have engineered a subunit BTV vaccine candidate based on proteins
      VP2, VP7, and NS1 of BTV-4 incorporated into avian reovirus (ARV) muNS-Mi
      microspheres (MS-VP2/MS-VP7/MS-NS1). IFNAR(-/-) mice immunized with MS-VP2/MS
      VP7/MS-NS1 without adjuvant generated significant levels of neutralizing
      antibodies specific to BTV-4. In addition, vaccination stimulated specific T cell
      responses, predominantly CD4+, against the virus. Immunized mice were fully
      protected against a homologous challenge with a lethal dose of BTV-4 and
      partially cross-protected against a heterologous challenge with a lethal dose of
      BTV-1. These results support MS-VP2/MS-VP7/MS-NS1 as a promising subunit vaccine
      candidate against multiple serotypes of BTV as well as the use of microspheres as
      an alternative delivery method with potent intrinsic adjuvant activity. 

PMID- 25057759
TI  - Development of a high-throughput pyrosequencing assay for monitoring temporal
      evolution and resistance associated variant emergence in the Hepatitis C virus
      protease coding-region.
AB  - A new generation of drugs targeting the non-structural (NS) proteins of the
      Hepatitis C virus (HCV) will substantially increase treatment success rates,
      reducing global infections. Amongst the NS proteins, the NS3 protease represents
      an important drug target, responsible for liberation of mature NS proteins from
      the nascent HCV polyprotein and suppression of host innate immunity. Despite
      this, the evolutionary stability of the genomic locus encoding the NS3 protease
      is poorly characterized in chronic HCV infection. To address this shortfall, we
      developed a high-throughput amplicon pyrosequencing protocol and utilised it to
      monitor NS3 protease coding-sequence evolution for over a decade in two patients.
      Although patient-specific evolutionary trends were apparent, the protease amino
      acid population consensus remained stable with a massive excess of synonymous
      mutations observed, confirming this locus is under strong purifying selection
      during chronic infection within individual patients. No evidence for continuous
      immune escape was detected. Additionally, both patients failed protease inhibitor
      (PI) therapy and protease sequence diversity pre- and post-therapy were also
      assessed. No baseline resistance associated variants (RAVs) contributed to
      treatment failure. Significant reductions in viral diversity were observed post
      PI therapy, indicating a population bottleneck occurred. The genetic vestiges of
      this bottleneck were still detectable 18months after therapy discontinuation.
      Although significant enrichment of the Q80L mutation was observed in one patient,
      genetic and phenotypic data reveal no detectable RAV persistence post-therapy
      failure. Together this investigation provides a sensitive and reproducible high
      throughput framework to interrogate viral sequence diversity at high-resolution,
      with potential applications for routine monitoring of treatment regimens. This
      study also reveals novel insights into the evolutionary processes that shape NS3
      sequence divergence in both chronic HCV infection and post PI-therapy failure. 

PMID- 25057761
TI  - Is there an association between asymmetry of carotid artery wall thickness
      (ACAWT) and cerebrovascular symptoms?
AB  - PURPOSE: Previous publications demonstrated that multi-detector-row computed
      tomography Angiography (MDCTA) can evaluate the carotid artery wall thickness
      (CAWT). The purpose of this work was to compare the asymmetry of CAWT between
      carotids in symptomatic and asymptomatic patients. MATERIAL AND METHODS: Sixty
      consecutive symptomatic (males 44; median age 64) and 60 asymptomatic sex- and
      age-matched patients were analysed by using a 40-detector-row CT system. CAWT was
      calculated for both carotids in each patient and the ratio between the thicker
      CAWT and the contra-lateral was calculated to obtain the ACAWT index. Bland
      Altman, logistic regression and receiver operating characteristic (ROC) curve
      analysis were calculated. RESULTS: The Bland-Altman plot demonstrates a very good
      agreement between measurements with a mean difference value of 3.4% and 95% CI
      from -8% to 14.8%. The ACAWT was significantly different between symptomatic and
      asymptomatic patients (with a p value of 0.0001). The ROC area under the curve
      was 0.742 (p = 0.001). Logistic regression model indicated that ACAWT, CAWT,
      stenosis degree, and fatty plaques were independent variables associated with
      cerebrovascular symptoms (p value, respectively, 0.0108, 0.0231, 0.0002, and
      0.013). CONCLUSION: Results of our study indicated that the index of asymmetry in
      the CAWT might be used as a further parameter to stratify the risk of symptoms
      related to carotid artery.

PMID- 25057763
TI  - Multidrug-resistant Acinetobacter baumannii strains carrying the bla(OxA-23) and
      the bla(GES-11) genes in a neonatology center in Tunisia.
AB  - Multidrug-resistant and difficult-to-treat Acinetobacter baumannii may be
      responsible for nosocomial infections. The production of carbapenem-hydrolyzing
      class D beta-lactamases (CHDLs) and extended-spectrum beta-lactamase (ESBLs) of
      the GES type possessing a carbapenemase activity has been increasingly reported
      worldwide in A. baumannii. The aim of this study was to analyze the resistance
      mechanisms of two carbapenem resistant A. baumannii clinical isolates recovered
      in a neonatology center in the center-east of Tunisia. Two carbapenem resistant
      A. baumannii isolates were recovered. The first isolate co-harbored the blaGES-11
      ESBL gene and the blaOxA-23 CHDL gene. Analyses of the genetic location indicated
      that the blaGES-11 gene was plasmid located (Gr6). However, the blaOxA-23 gene
      was located on the chromosome. The second strain had only the blaOxA-23 CHDL
      gene, which was plasmid located. This study showed the first description of the
      GES-type beta-lactamase in A. baumannii in Tunisia. 

PMID- 25057764
TI  - Co-occurrences between adolescent substance use and academic performance: school
      context influences a multilevel-longitudinal perspective.
AB  - A growing body of literature has linked substance use and academic performance
      exploring substance use as a predictor of academic performance or vice versa.
      This study uses a different approach conceptualizing substance use and academic
      performance as parallel outcomes and exploring two topics: its multilevel
      longitudinal association and school contextual effects on both outcomes. Using
      multilevel Confirmatory Factor Analysis and multilevel-longitudinal analyses, the
      empirical estimates relied on 7843 students nested in 114 schools (Add Health
      study). The main finding suggests that the correlation between substance use and
      academic performance was positive at the school level in contraposition to the
      negative relationship at the individual level. Additional findings suggest a
      positive effect of a school risk factor on substance use and a positive effect of
      academic pressure on academic performance. These findings represent a
      contribution to our understanding of how schools could affect the relationship
      between academic performance and substance use. 

PMID- 25057765
TI  - Development of high-performance printed organic field-effect transistors and
      integrated circuits.
AB  - Organic electronics is regarded as an important branch of future microelectronics
      especially suited for large-area, flexible, transparent, and green devices, with
      their low cost being a key benefit. Organic field-effect transistors (OFETs), the
      primary building blocks of numerous expected applications, have been intensively
      studied, and considerable progress has recently been made. However, there are
      still a number of challenges to the realization of high-performance OFETs and
      integrated circuits (ICs) using printing technologies. Therefore, in this
      perspective article, we investigate the main issues concerning developing high
      performance printed OFETs and ICs and seek strategies for further improvement.
      Unlike many other studies in the literature that deal with organic semiconductors
      (OSCs), printing technology, and device physics, our study commences with a
      detailed examination of OFET performance parameters (e.g., carrier mobility,
      threshold voltage, and contact resistance) by which the related challenges and
      potential solutions to performance development are inspected. While keeping this
      complete understanding of device performance in mind, we check the printed OFETs'
      components one by one and explore the possibility of performance improvement
      regarding device physics, material engineering, processing procedure, and
      printing technology. Finally, we analyze the performance of various organic ICs
      and discuss ways to optimize OFET characteristics and thus develop high
      performance printed ICs for broad practical applications. 

PMID- 25057766
TI  - Factors related to the number of fast food meals obtained by college meal plan
      students.
AB  - OBJECTIVES: This study tested whether days on campus, financial access through a
      meal plan, and health consciousness were associated with number of meals that
      college students obtained from fast food restaurants. PARTICIPANTS AND METHODS:
      In April 2013, all students currently enrolled in a meal plan were invited to
      participate in an online survey (N = 1,246). Students were asked to report the
      total number of meals eaten in the past week and where they obtained them.
      RESULTS: Negative binomial regression was used, and it was found that the number
      of meals obtained from fast food restaurants was positively associated with
      financial access and negatively associated with health consciousness. An
      association between days on campus and the number of meals obtained from fast
      food restaurants was not found. CONCLUSIONS: Increasing levels of health
      consciousness and reducing access to fast food restaurants through flex plans may
      reduce college students' consumption of fast food.

PMID- 25057767
TI  - Men's body depilation: an exploratory study of United States college students'
      preferences, attitudes, and practices.
AB  - Young men in Western cultures frequently engage in body depilation practices, but
      little is known regarding how such bodies are perceived. This exploratory study
      asked United States college students (N=238) to view six pictures of the same
      male body with different amounts of visible body hair and to indicate which body
      was most sexually attractive to themselves, to most men, and to most women. Both
      men and women chose a relatively hairless male body as the most sexually
      attractive. Women, however, thought men would choose a hairier body than men
      actually did. Most of the men reduced or removed body hair, especially from the
      pubic area. Questionnaire responses indicated that men and women had similar
      attitudes toward men's body hair, with both hair reduction and hair retention
      being socially acceptable. Men's body depilation, while still optional, may be
      becoming normative, at least among United States college students. 

PMID- 25057769
TI  - Folding energetics and oligomerization of polytopic alpha-helical transmembrane
      proteins.
AB  - While interactions of single-span transmembrane helices have been studied to a
      significant extent in the past years, the folding of polytopic alpha-helical
      transmembrane proteins, as well as their oligomerization, are far less analyzed
      and understood. The goal of the few thus far performed thermodynamic studies, in
      which unfolding of polytopic TM proteins was described, was to achieve a mild,
      potentially reversible unfolding process, to finally derive thermodynamic
      parameters for the reverse folding pathway. In the first part of this review, we
      summarize the studies analyzing the thermodynamic stability and folding pathways
      of polytopic transmembrane proteins. Based on these studies, we deduce some
      common principles, guiding transmembrane protein unfolding and folding, important
      for the design of future folding/unfolding studies. Furthermore, the discussed
      observations can conceptually guide an experimental search for proper in vitro
      transmembrane protein refolding conditions. In many of the resolved membrane
      protein structures, individual monomers interact to form higher ordered
      oligomers. In most cases, oligomerization of those monomeric units appears to be
      intimately linked to the protein function, and folding of the individual
      protomers might even occur only after interaction. In the second part of this
      review, we discuss folding pathways of oligomeric alpha-helical transmembrane
      proteins as well as causes and consequences of alpha-helical transmembrane
      protein oligomerization. 

PMID- 25057768
TI  - Role of polycomb group proteins in the DNA damage response--a reassessment.
AB  - A growing body of evidence suggests that Polycomb group (PcG) proteins, key
      regulators of lineage specific gene expression, also participate in the repair of
      DNA double-strand breaks (DSBs) but evidence for direct recruitment of PcG
      proteins at specific breaks remains limited. Here we explore the association of
      Polycomb repressive complex 1 (PRC1) components with DSBs generated by inducible
      expression of the AsiSI restriction enzyme in normal human fibroblasts. Based on
      immunofluorescent staining, the co-localization of PRC1 proteins with components
      of the DNA damage response (DDR) in these primary cells is unconvincing.
      Moreover, using chromatin immunoprecipitation and deep sequencing (ChIP-seq),
      which detects PRC1 proteins at common sites throughout the genome, we did not
      find evidence for recruitment of PRC1 components to AsiSI-induced DSBs. In
      contrast, the S2056 phosphorylated form of DNA-PKcs and other DDR proteins were
      detected at a subset of AsiSI sites that are predominantly at the 5' ends of
      transcriptionally active genes. Our data question the idea that PcG protein
      recruitment provides a link between DSB repairs and transcriptional repression. 

PMID- 25057770
TI  - Low-molecular-weight thiols in plants: functional and analytical implications.
AB  - Low-molecular-weight (LMW) thiols are a class of highly reactive compounds
      massively involved in the maintenance of cellular redox homeostasis. They are
      implicated in plant responses to almost all stress factors, as well as in the
      regulation of cellular metabolism. The most studied LMW thiols are glutathione
      and its biosynthetically related compounds (cysteine, gamma-glutamylcysteine,
      cysteinylglycine, and phytochelatins). Other LMW thiols are described in the
      literature, such as thiocysteine, cysteamine, homocysteine, lipoic acid, and many
      species-specific volatile thiols. Here, we review the known LMW thiols in plants,
      briefly describing their physico-chemical properties, their relevance in post
      translational protein modification, and recently-developed thiol detection
      methods. Current research points to a huge thiol biodiversity in plants and many
      species-specific and organ-specific thiols remain to be identified. Recent
      advances in technology should help researchers in this very challenging task,
      helping us to decipher the roles of thiols in plant metabolism. 

PMID- 25057772
TI  - Sex disparities in melanoma outcomes: the role of biology.
AB  - Melanoma outcomes differ between men and women even when adjusted for prognostic
      factors such as age, Breslow thickness, body site, ulceration, lymph node
      dissection, and for treatment, with men having poorer outcomes compared to women.
      The mechanisms underlying this disparity are not well understood. Behavioral
      differences between the sexes such as ultraviolet light exposure and health care
      services utilization have been suggested as contributing, and differences in
      endogenous biological processes such as immune function, hormonal regulation,
      oxidative stress response, vitamin D metabolism and sex chromosome gene
      expression have also been proposed as mechanisms. This review examines the
      cumulative evidence for biologically based processes that lead to differences in
      melanoma biology, including inherent sex-based differences in immune function,
      oxidative stress response and vitamin D metabolism; the complex interplay between
      sex hormones, the immune system and oxidative stress response; the effect of non
      random X chromosome inactivation on tumorigenesis; and the potential contribution
      of recently identified oncogenes on the Y chromosome. 

PMID- 25057771
TI  - Imatinib binding to human serum albumin modulates heme association and
      reactivity.
AB  - Imatinib, an inhibitor of the Bcr-Abl tyrosine kinase, is approximately 95% bound
      to plasma proteins, alpha1-acid glycoprotein (AGP) being the primary carrier.
      However, human serum albumin (HSA) may represent the secondary carrier of
      imatinib in pathological states characterized by low AGP levels, such as
      pancreatic cancer, hepatic cirrhosis, hepatitis, hyperthyroidism, nephrotic
      syndrome, malnutrition, and cachexia. Here, thermodynamics of imatinib binding to
      full-length HSA and its recombinant Asp1-Glu382 truncated form (containing only
      the FA1, FA2, FA6, and FA7 binding sites; trHSA), in the absence and presence of
      ferric heme (heme-Fe(III)), and the thermodynamics of heme-Fe(III) binding to HSA
      and trHSA, in the absence and presence of imatinib, has been investigated.
      Moreover, the effect of imatinib on kinetics of peroxynitrite detoxification by
      ferric human serum heme-albumin (HSA-heme-Fe(III)) and ferric truncated human
      serum heme-albumin (trHSA-heme-Fe(III)) has been explored. All data were obtained
      at pH 7.0, and 20.0  degrees C and 37.0  degrees C. Imatinib binding to the FA7
      site of HSA and trHSA inhibits allosterically heme-Fe(III) association to the FA1
      site and vice versa, according to linked functions. Moreover, imatinib binding to
      the secondary FA2 site of HSA-heme-Fe(III) inhibits allosterically peroxynitrite
      detoxification. Docking simulations and local structural comparison with other
      imatinib-binding proteins support functional data indicating the preferential
      binding of imatinib to the FA1 and FA7 sites of HSA, and to the FA2 and FA7 sites
      of HSA-heme-Fe(III). Present results highlight the allosteric coupling of the
      FA1, FA2, and FA7 sites of HSA, and may be relevant in modulating ligand binding
      and reactivity properties of HSA in vivo.

PMID- 25057773
TI  - Clarithromycin-Induced Torsades de Pointes.
AB  - Acquired QT prolongation can be caused by cardiac and noncardiac medications.
      Macrolides are known to prolong QT interval. Rarely, it can be fatal. We report a
      case of torsades de pointes in a patient taking clarithromycin as a part of
      Helicobacter pylori eradication regimen. 

PMID- 25057774
TI  - Exploring new dating approaches for parasites: the worldwide Apodanthaceae
      (Cucurbitales) as an example.
AB  - Gene trees of holoparasitic plants usually show distinctly longer branch lengths
      than seen in photosynthetic closest relatives. Such substitution rate jumps have
      made it difficult to infer the absolute divergence times of parasites. An
      additional problem is that parasite clades often lack a fossil record. Using
      nuclear and mitochondrial DNA sequences of Apodanthaceae, a worldwide family of
      endoparasites living inside Fabaceae and Salicaceae, we compared several dating
      approaches: (i) an uncorrelated lognormal (UCLN) model calibrated with outgroup
      fossils, (ii) ages of host lineages as a maximal age in an UCLN model, (iii) user
      assigned local clocks, and (iv) outgroup-fossil-calibrated random local clocks
      (RLC) with varying prior probabilities on the number of permitted rate changes
      (RLCu and RLCp models), a variable that has never been explored. The resulting
      dated phylogenies include all 10 species of the family, three in Australia, one
      in Iran, one in Africa, and the remainder in the Americas. All clock models infer
      a drastic rate jump between nonparasitic outgroups and Apodanthaceae, but since
      they distribute the rate heterogeneity differently, they result in much-different
      age estimates. Bayes factors using path and stepping-stone sampling indicated
      that the RLCp model fit poorly, while for matR, topologically unconstrained RLCu
      and UCLN models did not differ significantly and for 18S, the UCLN model was
      preferred. Under the equally well fitting models, the Apodanthaceae appear to be
      a relatively old clade, with a stem age falling between 65 and 81my, the
      divergence of Apodanthes from Pilostyles between 36 and 57my ago, and the crown
      age of the Australian clade 8-18my ago. In our study system, host-age
      calibrations did not yield well-constrained results, but they may work better in
      other parasite clades. For small data sets where statistical convergence can be
      reached even with complex models, random local clocks should be explored as an
      alternative to the exclusive reliance on UCLN clocks. 

PMID- 25057776
TI  - A pharma perspective on the systems medicine and pharmacology of inflammation.
AB  - Biological systems are complex and comprehend multiple scales of organisation.
      Hence, holistic approaches are necessary to capture the behaviour of these
      entities from the molecular and cellular to the whole organism level. This also
      applies to the understanding and treatment of different diseases. Traditional
      systems biology has been successful in describing different biological phenomena
      at the cellular level, but it still lacks of a holistic description of the multi
      scale interactions within the body. The importance of the physiological context
      is of particular interest in inflammation. Regulatory agencies have urged the
      scientific community to increase the translational power of bio-medical research
      and it has been recognised that modelling and simulation could be a path to
      follow. Interestingly, in pharma R&D, modelling and simulation has been employed
      since a long time ago. Systems pharmacology, and particularly physiologically
      based pharmacokinetic/pharmacodynamic models, serve as a suitable framework to
      integrate the available and emerging knowledge at different levels of the drug
      development process. Systems medicine and pharmacology of inflammation will
      potentially benefit from this framework in order to better understand
      inflammatory diseases and to help to transfer the vast knowledge on the molecular
      and cellular level into a more physiological context. Ultimately, this may lead
      to reliable predictions of clinical outcomes such as disease progression or
      treatment efficacy, contributing thereby to a better care of patients. 

PMID- 25057775
TI  - From spontaneous motor activity to coordinated behaviour: a developmental model.
AB  - In mammals, the developmental path that links the primary behaviours observed
      during foetal stages to the full fledged behaviours observed in adults is still
      beyond our understanding. Often theories of motor control try to deal with the
      process of incremental learning in an abstract and modular way without
      establishing any correspondence with the mammalian developmental stages. In this
      paper, we propose a computational model that links three distinct behaviours
      which appear at three different stages of development. In order of appearance,
      these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated
      behaviours, such as locomotion. The goal of our model is to address in silico
      four hypotheses that are currently hard to verify in vivo: First, the hypothesis
      that spinal reflex circuits can be self-organized from the sensor and motor
      activity induced by SMA. Second, the hypothesis that supraspinal systems can
      modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis
      that, since SMA is observed in an organism throughout its entire lifetime, it
      provides a mechanism suitable to maintain the reflex circuits aligned with the
      musculoskeletal system, and thus adapt to changes in body morphology. And fourth,
      the hypothesis that by changing the modulation of the reflex circuits over time,
      one can switch between different coordinated behaviours. Our model is tested in a
      simulated musculoskeletal leg actuated by six muscles arranged in a number of
      different ways. Hopping is used as a case study of coordinated behaviour. Our
      results show that reflex circuits can be self-organized from SMA, and that, once
      these circuits are in place, they can be modulated to achieve coordinated
      behaviour. In addition, our results show that our model can naturally adapt to
      different morphological changes and perform behavioural transitions. 

PMID- 25057777
TI  - Mathematical modeling of efficient protocols to control glioma growth.
AB  - In this paper we propose a mathematical model to describe the evolution of glioma
      cells taking into account the viscoelastic properties of brain tissue. The
      mathematical model is established considering that the glioma cells are of two
      phenotypes: migratory and proliferative. The evolution of the migratory cells is
      described by a diffusion-reaction equation of non Fickian type deduced
      considering a mass conservation law with a non Fickian migratory mass flux. The
      evolution of the proliferative cells is described by a reaction equation. A
      stability analysis that leads to the design of efficient protocols is presented.
      Numerical simulations that illustrate the behavior of the mathematical model are
      included. 

PMID- 25057778
TI  - Multimodel robust observer for an uncertain fish population model.
AB  - In this paper, a new method is proposed to design an observer for a nonlinear and
      uncertain system describing a continuous stage structured model of a harvested
      fish population. The aim is to get an estimation of the biomass of fishes by
      stage class. In the studied model the fishing effort is considered as a control
      term, the stage classes as states and the quantity of captured fish as a measured
      output. A Takagi-Sugeno multimodel first represents the uncertain non-linear
      model. Next, we develop a technique for designing a multimodel observer
      corresponding to this system, which attenuates the effect of modelling
      uncertainties and measurement noise on the state estimation. The design
      conditions are given in linear matrix inequalities (LMIs) terms that can be
      solved efficiently using existing numerical tools. The validity of the proposed
      method is illustrated by the simulation results.

PMID- 25057779
TI  - A microchip platform for interrogating tumor-macrophage paracrine signaling at
      the single-cell level.
AB  - It is increasingly recognized that infiltrating immune cells contribute to the
      pathogenesis of a wide range of solid tumors. The paracrine signaling between the
      tumor and the immune cells alters the functional state of individual tumor cells
      and, correspondingly, the anticipated response to radiation or chemotherapies,
      which is of great importance to clinical oncology. Here we present a high-density
      microchip platform capable of measuring a panel of paracrine signals associated
      with heterotypic tumor-immune cell interactions in the single-cell, pair-wise
      manner. The device features a high-content cell capture array of 5000+ sub
      nanoliter microchambers for the isolation of single and multi-cell combinations
      and a multi-plex antibody "barcode" array for multiplexed protein secretion
      analysis from each microchamber. In this work, we measured a panel of 16 proteins
      produced from individual glioma cells, individual macrophage cells and varying
      heterotypic multi-cell combinations of both on the same device. The results show
      changes of tumor cell functional phenotypes that cannot be explained by an
      additive effect from isolated single cells and, presumably, can be attributed to
      the paracrine signaling between macrophage and glioma cells. The protein
      correlation analysis reveals the key signaling nodes altered by tumor-macrophage
      communication. This platform enables the novel pair-wise interrogation of
      heterotypic cell-cell paracrine signaling at the individual cell level with an in
      depth analysis of the changing functional phenotypes for different co-culture
      cell combinations. 

PMID- 25057781
TI  - Effects of a conventional photocoagulator and a 3-ns pulse laser on
      preconditioning responses and retinal ganglion cell survival after optic nerve
      crush.
AB  - Previous research has demonstrated that laser photocoagulation treatment of the
      monkey retina affords protection against experimental glaucoma-induced retinal
      ganglion cell (RGC) loss in areas overlying laser spots. The underlying mechanism
      is unknown, but it is conceivable that the laser acted as a preconditioning
      stimulus, inducing localised, endogenous production of survival factors. The
      related purposes of the current study were firstly to examine whether
      preconditioning pathways are activated by either a conventional photocoagulator
      (CW) laser or a photoreceptor-sparing, short-pulse duration (2RT) laser in the
      rat retina, and secondly, to examine whether such preconditioning with either
      laser improves RGC survival after optic nerve (ON) crush. Pigmented rats were
      randomly assigned to one of three groups: sham, CW, 2RT. For the preconditioning
      study, laser spots were applied randomly to each retina in the posterior
      hemisphere of the eye taking care to avoid major blood vessels. Animals were
      killed at 6 h, 1d, and 7d after laser treatment, then analysed by qPCR,
      immunohistochemistry or Western immunoblotting. For the neuroprotection study,
      laser spots were administered to the mid-central retina of the right eye. The
      left eye served as a control. In two experiments, rats were lasered either 24 h
      or 7 days before ON crush, then killed a further 7 days later. Wholemount retinas
      were prepared and double labelling immunofluorescence performed. Nestin labelling
      allowed visualization of laser spots. Brn3a labelling identified viable RGCs.
      Photomicrographs of Brn3a labelling were taken in areas overlying nestin-positive
      laser spots. Quantification of Brn3a RGCs was then performed. Both the CW and 2RT
      lasers induced local glial cell activation. Moreover, both lasers induced
      localized upregulations of a number of well-documented (CNTF, FGF-2 Hsp27, pAKT)
      or putative (cFOS, ATF-3, IL-6) RGC survival factors. However, neither laser
      caused sustained increases in other factors associated with neuronal
      preconditioning, such as BDNF, Hsp70, IGF-1, bcl-2, and nitric oxide synthase. As
      regards neuroprotection, analysis of the data revealed that ON crush resulted in
      the loss of approximately 70% of Brn3a-labelled RGCs after 1 week. Neither the CW
      nor the 2RT laser augmented Brn3a-positive RGC survival in areas overlying and
      neighbouring laser spots. This was the case irrespective of whether lasering
      occurred 1 or 7 days before the ON crush. Our results showed that the CW and 2RT
      lasers both stimulated de novo synthesis of certain genes that are well-known RGC
      survival factors and/or that have been implicated in preconditioning-induced
      neuroprotection studies. Despite these findings, neither laser augmented survival
      of RGCs when delivered prior to ON crush. 

PMID- 25057782
TI  - Role of an extracellular chaperone, Clusterin in the pathogenesis of
      Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.
AB  - Pseudoexfoliation (PEX), an age related disorder is a prominent contributor to
      secondary glaucoma. Earlier studies have suggested involvement of clusterin in
      the development of PEX. We designed a case-control study to understand the role
      of clusterin single nucleotide polymorphisms (SNPs) in PEX and analyzed the role
      of risk alleles in the disease. Genotyping of SNPs in 136 PEX patients and 89
      controls of Indian origin revealed a genetic association between rs2279590 and
      PEX in Indian population with a p-value of 0.004. The high risk allele "G" at
      rs2279590 has an effect on clusterin mRNA expression. There was a twofold higher
      clusterin mRNA level in "GG" genotyped individuals in comparison to "AA"
      genotyped individuals (p = 0.039). Western blot and immunohistochemistry studies
      showed an upregulation of Clusterin protein in pseudoexfoliation glaucoma (PXG)
      affected individuals in both aqueous humor and lens capsules respectively.
      Together, our results reveal that rs2279590 was found to be associated with PEX
      in Indian population and the risk allele mediates an allele specific upregulation
      of the clusterin mRNA. Moreover, upregulation of Clusterin protein in PXG
      individuals augments further protein deposition. 

PMID- 25057783
TI  - Open-shell character and second hyperpolarizabilities of one-dimensional
      chromium(II) chains: size dependence and bond-length alternation effect.
AB  - Using the long-range corrected spin-unrestricted density functional theory (LC
      UBLYP) method, we have investigated the longitudinal third-order nonlinear
      optical (NLO) properties, i.e., the second hyperpolarizabilities gamma of open
      shell singlet one-dimensional (1D) extended metal atom chain (EMAC) systems,
      chromium(II) chains Cr(II)2n (n = 1-4), with different metal-metal bond lengths
      from the viewpoint of the open-shell character dependences of each d orbital
      contribution (dsigma, dpi, ddelta) to gamma and of the chain-length dependence of
      gamma. It turns out that the chain length dependences of the open-shell
      characters of dpi and ddelta orbitals at any metal-metal bond length are
      negligible, while the dsigma open-shell character decreases as a function of
      chain length. The systems display bell-shaped behaviors of gamma as a function of
      the metal-metal bond length, in which the gamma values attain maxima for
      intermediate dsigma open-shell character. The maximum gamma value (gammamax)
      exhibits remarkable enhancement as a function of chain length. It is also found
      that the bond length alternation (BLA) significantly affects the gamma values and
      their chain-length dependences. The present results provide the guiding
      principles for designing transition-metal complexes with open-shell singlet 1D
      metallic chains exhibiting large third-order optical nonlinearity. 

PMID- 25057784
TI  - The relationship between bone mineral density and blood pressure in the Korean
      elderly population: the Korea National Health and Nutrition Examination Survey,
      2008-2011.
AB  - It is not clear whether the inverse relationship between bone mineral density
      (BMD) and blood pressure (BP) could be generalizable to the general elderly
      population. We used data from the fourth and fifth Korea National Health and
      Nutrition Examination Survey. The study sample consisted of 8439 men and
      postmenopausal women aged 50 years and older. We evaluated the relationship
      between BMD and BP. When adjusted for covariates, femur neck T-score [coefficient
      = -0.391, 95% confidence interval (CI) -0.766 to -0.016, p = 0.041] had an
      inverse relationship with diastolic BP (DBP), whereas lumbar spine BMD
      (coefficient = 0.395, 95% CI 0.058-7.752, p = 0.047) and T-score (coefficient =
      0.458, 95% CI 0.005-0.911, p = 0.047) had a positive relationship with systolic
      BP (SBP). When adjusted for confounding factors, SBP (128.67 +/- 0.979 mmHg
      versus 126.36 +/- 0.545 mmHg, p = 0.026) and DBP (78.8 +/- 0.622 mmHg versus
      77.27 +/- 0.283 mmHg, p = 0.016) were significantly higher in femur neck
      osteoporosis subjects than non-osteoporosis subjects. However, there were no
      differences in BP in relation to lumbar spine osteoporosis. Femur neck
      osteoporosis (odds ratio = 1.422, 95% CI 1.107-1.827, p = 0.006) had a
      significant and positive relationship with hypertension, whereas the other
      parameters of BMD were not significantly related to hypertension. In conclusion,
      higher BP and hypertension were significantly and positively correlated with
      femur neck osteoporosis in men and postmenopausal women aged 50 years and older.

PMID- 25057785
TI  - Unique regioselectivity in the C(sp3)-H alpha-alkylation of amines: the
      benzoxazole moiety as a removable directing group.
AB  - The benzoxazol-2-yl- substituent was found to act as a removable activating and
      directing group in the Ir-catalyzed alkylation of C(sp(3))-H bonds adjacent to
      nitrogen in secondary amines. It can be easily introduced by oxidative coupling
      or by an SNAr reaction, and it can be removed by hydroxide or by hydride
      reduction. For 1,2,3,4-tetrahydroisoquinolines, activation exclusively takes
      place in the 3-position. A variety of activated as well as unactivated terminal
      olefins are suitable reaction partners. 

PMID- 25057786
TI  - Multiplexed LC-MS/MS assay for urine albumin.
AB  - Urinary excretion of albumin is a major diagnostic and prognostic marker of renal
      dysfunction and cardiovascular disease; therefore, accurate measurement of urine
      albumin is vital to clinical diagnosis. Although intermethod differences and
      analyte heterogeneity have been reported for urine albumin measurements, accuracy
      assessments of the available methods have been hindered by the lack of a
      reference system, including reference measurement procedures and reference
      materials, for this clinical analyte. To address the need for a reference
      measurement system for urine albumin, we have developed a candidate reference
      measurement procedure that utilizes isotope dilution-mass spectrometry (ID-MS)
      and multiple reaction monitoring (MRM) to quantify full-length urine albumin in a
      targeted mass spectrometric-based approach. The reference measurement procedure
      incorporates an isotopically labeled ((15)N) full-length recombinant human serum
      albumin ((15)N-rHSA) material as the internal standard, which permits the
      absolute quantitation of albumin in urine. A total of 11 peptides with two
      transitions per peptide were selected from the tryptic digestion of human serum
      albumin on the basis of retention time reproducibility, peak intensity, and the
      degree of HSA sequence coverage. In addition to method validation, the generated
      calibration curves were used to determine the albumin content in pooled human
      urine samples to access the accuracy of the MS-based urine albumin quantitation
      method.

PMID- 25057787
TI  - Metazoan parasite infection in the swordfish, Xiphias gladius, from the
      Mediterranean Sea and comparison with Atlantic populations: implications for its
      stock characterization.
AB  - Thirteen parasite taxa were identified in the Mediterranean swordfish by
      morphological and genetic/molecular methods. The comparison of the identified
      parasite taxa and parasitic infection values observed in the Mediterranean
      swordfish showed statistically significant differences with respect to those
      reported for its Atlantic populations. A stepwise Linear Discriminant Analysis of
      the individual fish examined showed a separation among three groups: one
      including fish from the Mediterranean Sea (CTS, STS, and IOS); one consisting of
      fish from the Central South (CS), Eastern Tropical (ET), and Equatorial (TEQ)
      Atlantic; and a third comprising the fish sampled from the North-West Atlantic
      (NW); the CN Atlantic sample was more similar to the first group rather than to
      the other Atlantic ones. The nematodes Hysterothylacium petteri and Anisakis
      pegreffii were the species that contributed most to the characterization of the
      Mediterranean swordfish samples with respect to these Atlantic ones. Anisakis
      brevispiculata, A. physeteris, A. paggiae, Anisakis sp. 2, Hysterothylacium
      incurvum, Hepatoxylon trichiuri, Sphyriocephalus viridis, and their high
      infection levels were associated with the swordfish from the Central and the
      Southern Atlantic areas. Finally, H. corrugatum, A. simplex (s.s.),
      Rhadinorhynchus pristis, and Bolbosoma vasculosum were related to the fish from
      the North-West (NW) Atlantic area. These results indicate that some parasites,
      particularly Anisakis spp. larvae identified by genetic markers, could be used as
      "biological tags" and support the existence of a Mediterranean swordfish stock. 

PMID- 25057788
TI  - Diastereodivergent organocatalytic asymmetric vinylogous Michael reactions.
AB  - One of the major challenges of modern asymmetric catalysis is the ability to
      selectively control the formation of all diastereoisomers of reaction products
      possessing multiple stereocenters. Pioneers of such diastereodivergent catalytic
      asymmetric processes have focused on reactions where the newly formed stereogenic
      centres are proximal to the active carbonyl group. To date, however,
      diastereodivergent reactions at remote positions remain an unmet challenge.
      Herein, we describe a catalyst-controlled diastereodivergence in the formation of
      remote stereocenters in the direct vinylogous Michael reactions of beta, gamma
      unsaturated butenolides to alpha, beta-unsaturated ketones. The reactions are
      enabled by two complementary, non-enantiomeric multifunctional catalysts, which
      mutually activate and organise both reactants, affording either the syn- or anti
      adduct with high diastereo- and enantioselectivity. These two catalytic systems
      are also applicable in the Mukaiyama-Michael reactions and tandem Michael-Michael
      reactions. 

PMID- 25057789
TI  - Foxa1 and Foxa2 regulate alpha-cell differentiation, glucagon biosynthesis, and
      secretion.
AB  - The Forkhead box A transcription factors are major regulators of glucose
      homeostasis. They show both distinct and redundant roles during pancreas
      development and in adult mouse beta-cells. In vivo ablation studies have revealed
      critical implications of Foxa1 on glucagon biosynthesis and requirement of Foxa2
      in alpha-cell terminal differentiation. In order to examine the respective role
      of these factors in mature alpha-cells, we used small interfering RNA (siRNA)
      directed against Foxa1 and Foxa2 in rat primary pancreatic alpha-cells and rodent
      alpha-cell lines leading to marked decreases in Foxa1 and Foxa2 mRNA levels and
      proteins. Both Foxa1 and Foxa2 control glucagon gene expression specifically
      through the G2 element. Although we found that Foxa2 controls the expression of
      the glucagon, MafB, Pou3f4, Pcsk2, Nkx2.2, Kir6.2, and Sur1 genes, Foxa1 only
      regulates glucagon gene expression. Interestingly, the Isl1 and Gipr genes were
      not controlled by either Foxa1 or Foxa2 alone but by their combination. Foxa1 and
      Foxa2 directly activate and bind the promoter region the Nkx2.2, Kir6.2 and Sur1,
      Gipr, Isl1, and Pou3f4 genes. We also demonstrated that glucagon secretion is
      affected by the combined effects of Foxa1 and Foxa2 but not by either one alone.
      Our results indicate that Foxa1 and Foxa2 control glucagon biosynthesis and
      secretion as well as alpha-cell differentiation with both common and unique
      target genes.

PMID- 25057791
TI  - Visualization of corticotropin-releasing factor neurons by fluorescent proteins
      in the mouse brain and characterization of labeled neurons in the paraventricular
      nucleus of the hypothalamus.
AB  - Corticotropin-releasing factor (CRF) is the key regulator of the hypothalamic
      pituitary-adrenal axis. CRF neurons cannot be distinguished morphologically from
      other neuroendocrine neurons in the paraventricular nucleus of the hypothalamus
      (PVH) without immunostaining. Thus, we generated a knock-in mouse that expresses
      modified yellow fluorescent protein (Venus) in CRF neurons (CRF-Venus), and yet
      its expression is driven by the CRF promoter and responds to changes in the
      interior milieu. In CRF-Venus, Venus-expressing neurons were distributed in brain
      regions harboring CRF neurons, including the PVH. The majority of Venus
      expressing neurons overlapped with CRF-expressing neurons in the PVH, but many
      neurons expressed only Venus or CRF in a physiological glucocorticoid condition.
      After glucocorticoid deprivation, however, Venus expression intensified, and most
      Venus neurons coexpressed CRF. Conversely, Venus expression was suppressed by
      excess glucocorticoids. Expression of copeptin, a peptide encoded within the
      vasopressin gene, was induced in PVH-Venus neurons by glucocorticoid deprivation
      and suppressed by glucocorticoid administration. Thus, Venus neurons
      recapitulated glucocorticoid-dependent vasopressin expression in PVH-CRF neurons.
      Noradrenaline increased the frequency of glutamate-dependent excitatory
      postsynaptic currents recorded from Venus-expressing neurons in the voltage clamp
      mode. In addition, the CRF-iCre knock-in mouse was crossed with a CAG-CAT-EGFP
      reporter mouse to yield the Tg(CAG-CAT-EGFP/wt);CRF(iCre/wt) (EGFP/CRF-iCre)
      mouse, in which enhanced green fluorescent protein (EGFP) is driven by the CAG
      promoter. EGFP was expressed more constitutively in the PVH of EGFP/CRF-iCre
      mice. Thus, CRF-Venus may have an advantage for monitoring dynamic changes in CRF
      neurons and CRF networks in different glucocorticoid states.

PMID- 25057792
TI  - Early intervention with intranasal NPY prevents single prolonged stress-triggered
      impairments in hypothalamus and ventral hippocampus in male rats.
AB  - Intranasal administration of neuropeptide Y (NPY) is a promising treatment
      strategy to reduce traumatic stress-induced neuropsychiatric symptoms of
      posttraumatic stress disorder (PTSD). We evaluated the potential of intranasal
      NPY to prevent dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, a
      core neuroendocrine feature of PTSD. Rats were exposed to single prolonged stress
      (SPS), a PTSD animal model, and infused intranasally with vehicle or NPY
      immediately after SPS stressors. After 7 days undisturbed, hypothalamus and
      hippocampus, 2 structures regulating the HPA axis activity, were examined for
      changes in glucocorticoid receptor (GR) and CRH expression. Plasma ACTH and
      corticosterone, and hypothalamic CRH mRNA, were significantly higher in the
      vehicle but not NPY-treated group, compared with unstressed controls. Although
      total GR levels were not altered in hypothalamus, a significant decrease of GR
      phosphorylated on Ser232 and increased FK506-binding protein 5 mRNA were observed
      with the vehicle but not in animals infused with intranasal NPY. In contrast, in
      the ventral hippocampus, only vehicle-treated animals demonstrated elevated GR
      protein expression and increased GR phosphorylation on Ser232, specifically in
      the nuclear fraction. Additionally, SPS-induced increase of CRH mRNA in the
      ventral hippocampus was accompanied by apparent decrease of CRH peptide
      particularly in the CA3 subfield, both prevented by NPY. The results show that
      early intervention with intranasal NPY can prevent traumatic stress-triggered
      dysregulation of the HPA axis likely by restoring HPA axis proper negative
      feedback inhibition via GR. Thus, intranasal NPY has a potential as a noninvasive
      therapy to prevent negative effects of traumatic stress.

PMID- 25057790
TI  - Selective deletion of leptin receptors in gonadotropes reveals activin and GnRH
      binding sites as leptin targets in support of fertility.
AB  - The adipokine, leptin (LEP), is a hormonal gateway, signaling energy stores to
      appetite-regulatory neurons, permitting reproduction when stores are sufficient.
      Dual-labeling for LEP receptors (LEPRs) and gonadotropins or GH revealed a 2-fold
      increase in LEPR during proestrus, some of which was seen in LH gonadotropes. We
      therefore investigated LEPR functions in gonadotropes with Cre-LoxP technology,
      deleting the signaling domain of the LEPR (Lepr-exon 17) with Cre-recombinase
      driven by the rat LH-beta promoter (Lhbeta-cre). Selectivity of the deletion was
      validated by organ genotyping and lack of LEPR and responses to LEP by mutant
      gonadotropes. The mutation had no impact on growth, body weight, the timing of
      puberty, or pregnancy. Mutant females took 36% longer to produce their first
      litter and had 50% fewer pups/litter. When the broad impact of the loss of
      gonadotrope LEPR on all pituitary hormones was studied, mutant diestrous females
      had reduced serum levels of LH (40%), FSH (70%), and GH (54%) and mRNA levels of
      Fshbeta (59%) and inhibin/activin beta A and beta B (25%). Mutant males had
      reduced serum levels of GH (74%), TSH (31%), and prolactin (69%) and mRNA levels
      of Gh (31%), Ghrhr (30%), Fshbeta (22%), and glycoprotein alpha-subunit (Cga)
      (22%). Serum levels of LEP and ACTH and mRNA levels of Gnrhr were unchanged.
      However, binding to GnRH receptors was reduced in LEPR-null LH or FSH
      gonadotropes by 82% or 89%, respectively, in females (P < .0001) and 27% or 53%,
      respectively, in males (P < .03). This correlated with reductions in GnRH
      receptor protein immunolabeling, suggesting that LEP's actions may be
      posttranscriptional. Collectively, these studies highlight the importance of LEP
      to gonadotropes with GnRH-binding sites and activin as potential targets. LEP may
      modulate population growth, adjusting the number of offspring to the availability
      of food supplies.

PMID- 25057793
TI  - Glucocorticoids induce gastroparesis in mice through depletion of l-arginine.
AB  - Glucocorticoids (GCs) constitute a highly pleiotropic class of drugs
      predominantly employed in the treatment of inflammatory diseases. In our search
      for new mechanisms of action, we identified a hitherto unknown effect of GCs in
      the gastrointestinal tract. We found that oral administration of dexamethasone
      (Dex) to mice caused an enlargement of the stomach due to the induction of
      gastroparesis and that this effect was abolished in GR(dim) mice carrying the
      A458T mutation in the GC receptor (GR). Gastroparesis was unrelated to the
      enhanced gastric acid secretion observed after Dex treatment, although both
      effects were mediated by the same molecular mechanism of the GR. Using
      conditional GR-knockout mice, we could further rule out that GC effects on
      enterocytes or myeloid cells were involved in the induction of gastroparesis. In
      contrast, we found that Dex upregulated arginase 2 (Arg2) in the stomach both at
      the mRNA and protein level. This suggests that GC treatment leads to a depletion
      of l-arginine thereby impeding the production of nitric oxide (NO), which is
      required for gastric motility. We tested this hypothesis by supplementing the
      drinking water of the mice with exogenous l-arginine to compensate for the
      presumed shortage of this major substrate of NO synthases. Importantly, this
      measure completely prevented both the enlargement of the stomach and the
      induction of gastroparesis after Dex treatment. Our findings raise considerations
      of combining orally applied GCs with l-arginine to improve tolerability of GC
      treatment and provide a possible explanation for the antiemetic effects of GCs
      widely exploited in chemotherapy.

PMID- 25057794
TI  - beta-cell induction in vivo in severely diabetic male mice by changing the
      circulating levels and pattern of the ratios of estradiol to androgens.
AB  - Previously we have generated transgenic (Tg) mice developing severe diabetes
      early in life with a profound depletion of beta-cells with beta-cell-directed
      expression of inducible cAMP early repressor-Igamma. Only male mice continue to
      demonstrate hyperglycemia throughout life. To investigate this sexual dimorphism,
      we treated severely diabetic male Tg mice with orchiectomy (ORX) or 17beta
      estradiol (E2) pellet implantation alone or in combination with ORX and E2
      implantation to change the circulating levels and patterns of the ratio of
      estradiol to androgens. In the Tg-ORX group, the blood-glucose levels decreased
      to a certain level within several weeks but never reached the female Tg-control
      level. In contrast, the Tg-ORX+E2 or Tg-E2 group showed a more rapid drop in
      blood glucose to the basal level with a substantial increase in beta-cells, thus
      preventing the occurrence of severe diabetes in the male mice. The beta-cells,
      not only within islet but also in and adjacent to ducts and scattered beta-cell
      clusters, were strongly induced by 1 week after treatment, and the islet
      morphology dramatically changed. Enhanced beta-cell induction in the ducts
      occurred concomitantly with markedly increased levels of pancreatic duodenal
      homeobox-1 and related transcription factors. The glucose-lowering and beta-cell
      increasing effects were independent of the age at which the treatment is started.
      These data provide evidence that the circulating level of E2 and the ratio of E2
      to T greatly affect the blood glucose levels, the beta-cell induction, and the
      islet morphology in diabetic male Tg mice. This novel mechanism offers great
      potential for developing strategies to increase the number of beta-cells in vivo.

PMID- 25057795
TI  - Neurokinin B induces c-fos transcription via protein kinase C and activation of
      serum response factor and Elk-1 in immortalized GnRH neurons.
AB  - Mutations in neurokinin B (NKB) and its receptor, NK3R, were identified in human
      patients with hypogonadotropic hypogonadism, a disorder characterized by lack of
      puberty and infertility. Further studies have suggested that NKB acts at the
      level of the hypothalamus to control GnRH neuron activity, either directly or
      indirectly. We recently reported that treatment with senktide, a NK3R agonist,
      induced GnRH secretion and expression of c-fos mRNA in GT1-7 cells. Here, we map
      the responsive region in the murine c-fos promoter to between -400 and -200 bp,
      identify the signal transducer and activator of transcription (STAT) (-345) and
      serum response element (-310) sites as required for induction, a modulatory role
      for the Ets site (-318), and show that induction is protein kinase C dependent.
      Using gel shift and Gal4 assays, we further show that phosphorylation of Elk-1
      leads to binding to DNA in complex with serum response factor at serum response
      element and Ets sites within the c-fos promoter. Thus, we determine molecular
      mechanisms involved in NKB regulation of c-fos induction, which may play a role
      in modulation of GnRH neuron activation.

PMID- 25057796
TI  - Phosphate interacts with PTHrP to regulate endochondral bone formation.
AB  - Phosphate and parathyroid hormone related peptide (PTHrP) are required for normal
      growth plate maturation. Hypophosphatemia impairs hypertrophic chondrocyte
      apoptosis leading to rachitic expansion of the growth plate; however, the effect
      of phosphate restriction on chondrocyte differentiation during endochondral bone
      formation has not been examined. Investigations were, therefore, undertaken to
      address whether phosphate restriction alters the maturation of embryonic d15.5
      murine metatarsal elements. Metatarsals cultured in low phosphate media exhibited
      impaired chondrocyte differentiation, analogous to that seen with PTHrP-treatment
      of metatarsals cultured in control media. Because phosphate restriction acutely
      increases PTHrP expression in cultured metatarsals, studies were undertaken to
      determine if this increase in PTHrP plays a pathogenic role in the impaired
      chondrocyte differentiation observed under low phosphate conditions. In contrast
      to what was observed with wild-type metatarsal elements, phosphate restriction
      did not impair the differentiation of metatarsals isolated from PTHrP
      heterozygous or PTHrP knockout mice. In vivo studies in postnatal mice
      demonstrated that PTHrP haploinsufficiency also prevents the impaired
      hypertrophic chondrocyte apoptosis observed with phosphate restriction. To
      determine how signaling through the PTH/PTHrP receptor antagonizes the pro
      apoptotic effects of phosphate, investigations were performed in primary murine
      hypertrophic chondrocytes. Receptor activation impaired phosphate-induced Erk1/2
      phosphorylation specifically in the mitochondrial fraction and decreased levels
      of mitochondrial Bad, while increasing cytosolic phospho-Bad. Thus, these data
      demonstrate that phosphate restriction attenuates chondrocyte differentiation as
      well as impairing hypertrophic chondrocyte apoptosis and implicate a functional
      role for the PTH/PTHrP signaling pathway in the abnormalities in chondrocyte
      differentiation and hypertrophic chondrocyte apoptosis observed under phosphate
      restricted conditions.

PMID- 25057797
TI  - Virio- and bacterioplankton microscale distributions at the sediment-water
      interface.
AB  - The marine sediment-water interface is an important location for microbially
      controlled nutrient and gas exchange processes. While microbial distributions on
      the sediment side of the interface are well established in many locations, the
      distributions of microbes on the water side of the interface are less well known.
      Here, we measured that distribution for marine virio- and bacterioplankton with a
      new two-dimensional technique. Our results revealed higher heterogeneity in
      sediment-water interface biomass distributions than previously reported with a
      greater than 45- and 2500-fold change cm(-1) found within bacterial and viral
      subpopulations compared to previous maxima of 1.5- and 1.4-fold cm(-1) in
      bacteria and viruses in the same environments. The 45-fold and 2500-fold changes
      were due to patches of elevated and patches of reduced viral and bacterial
      abundance. The bacterial and viral hotspots were found over single and multiple
      sample points and the two groups often coincided whilst the coldspots only
      occurred over single sample points and the bacterial and viral abundances showed
      no correlation. The total mean abundances of viruses strongly correlated with
      bacteria (r = 0.90, p<0.0001, n = 12) for all three microplates (n = 1350).
      Spatial autocorrelation analysis via Moran's I and Geary's C revealed non-random
      distributions in bacterial subpopulations and random distributions in viral
      subpopulations. The variable distributions of viral and bacterial abundance over
      centimetre-scale distances suggest that competition and the likelihood of viral
      infection are higher in the small volumes important for individual cell
      encounters than bulk measurements indicate. We conclude that large scale
      measurements are not an accurate measurement of the conditions under which
      microbial dynamics exist. The high variability we report indicates that few
      microbes experience the 'average' concentrations that are frequently measured.

PMID- 25057799
TI  - Liposomal nitrooxy-doxorubicin: one step over caelyx in drug-resistant human
      cancer cells.
AB  - In this work we prepared and characterized two liposomal formulations of a
      semisynthetic nitric oxide (NO)-releasing doxorubicin (Dox), called nitrooxy-Dox
      (NitDox), which we previously demonstrated to be cytotoxic in Dox-resistant human
      colon cancer cells. Liposomes with 38.2% (Lip A) and 19.1% (Lip B) cholesterol
      were synthesized: both formulations had similar size and zeta potential values
      and caused the same intracellular distribution of free NitDox, but Lip B
      accumulated and released NitDox more efficiently. In Dox-resistant human colon
      cancer cells, Lip A and Lip B exhibited a more favorable kinetics of drug uptake
      and NO release, and a stronger cytotoxicity than Dox and free NitDox. While
      Caelyx, one of the liposomal Dox formulations approved for breast and ovary
      tumors treatment, was ineffective in Dox-resistant breast/ovary cancer cells, Lip
      B, and to a lesser extent Lip A, still exerted a significant cytotoxicity in
      these cells. This event was accompanied in parallel by a higher release of NO,
      which caused nitration of P-glycoprotein (Pgp) and multidrug resistance related
      protein 1 (MRP1), two transporters involved in Dox efflux, and impaired their
      pump activity. By doing so, the efflux kinetics of Dox after treatment with Lip B
      was markedly slowed down and the intracellular accumulation of Dox was increased
      in breast and ovary drug-resistant cells. We propose these liposomal formulations
      of NitDox as new tools with a specific indication for tumors overexpressing Pgp
      and MRP1. 

PMID- 25057800
TI  - Structure-activity relationship studies and discovery of a potent transient
      receptor potential vanilloid (TRPV1) antagonist 4-[3-chloro-5-[(1S)-1,2
      dihydroxyethyl]-2-pyridyl]-N-[5-(trifluoromethyl)-2-pyridyl]-3,6-dihydro-2H
      pyridine-1-carboxamide (V116517) as a clinical candidate for pain management.
AB  - A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared
      and evaluated in an effort to optimize properties of previously described lead
      compounds from piperazinecarboxamide series. The compounds were evaluated for
      their ability to block capsaicin and acid-induced calcium influx in CHO cells
      expressing human TRPV1. The most potent of these TRPV1 antagonists were further
      characterized in pharmacokinetic, efficacy, and body temperature studies. On the
      basis of its pharmacokinetic, in vivo efficacy, safety, and toxicological
      properties, compound 37 was selected for further evaluation in human clinical
      trials. 

PMID- 25057801
TI  - Cross-catalytic peptide nucleic acid (PNA) replication based on templated
      ligation.
AB  - We report the first PNA self-replicating system based on template directed cross
      catalytic ligation, a process analogous to biological replication. Using two
      template PNAs and four pentameric precursor PNAs, all four possible carbodiimide
      assisted amide ligation products were detected and identified by HPLC and MALDI
      TOF analysis. We conclude that the two template complementary reaction products
      are generated via cross-catalysis, while the other two self-complementary (and in
      principle auto-catalytic) products are formed via intra-complex coupling between
      the two sets of complementary PNA precursors. Cross-catalytic product formation
      followed product inhibited kinetics, but approximately two replication rounds
      were observed. Analogous but less efficient replication was found for a similar
      tetrameric system. These results demonstrate that simpler nucleobase replication
      systems than natural oligonucleotides are feasible, thereby strengthening the
      foundation for the discussion of a possible role for PNA (like) genetic material
      in the prebiotic evolution of life and lay the ground for further studies into
      evolution of such potentially prebiotic systems. 

PMID- 25057798
TI  - Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of
      adult-onset disease through the female germline.
AB  - Environmental compounds including fungicides, plastics, pesticides, dioxin and
      hydrocarbons can promote the epigenetic transgenerational inheritance of adult
      onset disease in future generation progeny following ancestral exposure during
      the critical period of fetal gonadal sex determination. This study examined the
      actions of the pesticide methoxychlor to promote the epigenetic transgenerational
      inheritance of adult-onset disease and associated differential DNA methylation
      regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were
      transiently exposed to methoxychlor during fetal gonadal development (gestation
      days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3
      (great-grand offspring) generation progeny for control (vehicle exposed) and
      methoxychlor lineage offspring. There were increases in the incidence of kidney
      disease, ovary disease, and obesity in the methoxychlor lineage animals. In
      females and males the incidence of disease increased in both the F1 and the F3
      generations and the incidence of multiple disease increased in the F3 generation.
      There was increased disease incidence in F4 generation reverse outcross (female)
      offspring indicating disease transmission was primarily transmitted through the
      female germline. Analysis of the F3 generation sperm epigenome of the
      methoxychlor lineage males identified differentially DNA methylated regions (DMR)
      termed epimutations in a genome-wide gene promoters analysis. These epimutations
      were found to be methoxychlor exposure specific in comparison with other exposure
      specific sperm epimutation signatures. Observations indicate that the pesticide
      methoxychlor has the potential to promote the epigenetic transgenerational
      inheritance of disease and the sperm epimutations appear to provide exposure
      specific epigenetic biomarkers for transgenerational disease and ancestral
      environmental exposures. 

PMID- 25057802
TI  - Are patients with erythema migrans who have leukopenia and/or thrombocytopenia
      coinfected with Anaplasma phagocytophilum or tick-borne encephalitis virus?
AB  - Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic
      anaplasmosis (HGA) are endemic in central part of Slovenia. We tested the
      hypothesis that patients with erythema migrans (EM) from this region, who have
      leukopenia and/or thrombocytopenia (typical findings in HGA and in the initial
      phase of TBE but not in patients with LB) are coinfected with Anaplasma
      phagocytophilum and/or with TBE virus, i.e. that cytopenia is a result of
      concomitant HGA or the initial phase of TBE. Comparison of clinical and
      laboratory findings for 67 patients with EM who disclosed
      leukopenia/thrombocytopenia with the corresponding results in sex- and age
      matched patients with EM and normal blood cell counts revealed no differences. In
      addition, patients with typical EM and leukopenia and/or thrombocytopenia tested
      negative for the presence of IgM and IgG antibodies to TBE virus by ELISA as well
      as for the presence of specific IgG antibodies to A. phagocytophilum antigens by
      IFA in acute and convalescent serum samples. Thus, none of 67 patients (95% CI: 0
      to 5.3%) with typical EM (the presence of this skin lesion attests for early Lyme
      borreliosis and is the evidence for a recent tick bite) was found to be
      coinfected with A. phagocytophilum or had a recent primary infection with TBE
      virus. The findings in the present study indicate that in Slovenia, and probably
      in other European countries endemic for LB, TBE and HGA, patients with early LB
      are rarely coinfected with the other tick-transmitted agents. 

PMID- 25057803
TI  - Treatment of alveolar-pleural fistula with endobronchial application of synthetic
      hydrogel.
AB  - BACKGROUND: Alveolar-pleural fistula with persistent air leak is a common problem
      causing significant morbidity, prolonged hospital stay, and increased health-care
      costs. When conventional therapy fails, an alternative to prolonged chest-tube
      drainage or surgery is needed. New bronchoscopic techniques have been developed
      to close the air leak by reducing the flow of air through the leak. The objective
      of this study was to analyze our experience with bronchoscopic application of a
      synthetic hydrogel for the treatment of such fistulas. METHODS: We conducted a
      retrospective study of patients with alveolar-pleural fistula with persistent air
      leaks treated with synthetic hydrogel application via flexible bronchoscopy.
      Patient characteristics, underlying disease, and outcome of endoscopic treatment
      were analyzed. RESULTS: Between January 2009 and December 2013, 22 patients (14
      men, eight women; mean age +/- SD, 62 +/- 10 years) were treated with one to
      three applications of a synthetic hydrogel per patient. The primary etiology of
      persistent air leak was necrotizing pneumonia (n = 8), post-thoracic surgery (n =
      6), bullous emphysema (n = 5), idiopathic interstitial pneumonia (n = 2), and
      sarcoidosis (n = 1). Nineteen patients (86%) had complete resolution of the air
      leak, leading to successful removal of chest tube a mean ( +/- SD) of 4.3 +/- 0.9
      days after last bronchoscopic application. The procedure was very well tolerated,
      with two patients coughing up the hydrogel and one having hypoxemia requiring
      bronchoscopic suctioning. CONCLUSIONS: Bronchoscopic administration of a
      synthetic hydrogel is an effective, nonsurgical, minimally invasive intervention
      for patients with persistent pulmonary air leaks secondary to alveolar-pleural
      fistula.

PMID- 25057804
TI  - Does hip displacement influence health-related quality of life in children with
      cerebral palsy?
AB  - OBJECTIVE: To evaluate the association of hip lateralisation with health-related
      quality of life (HRQL) in children with cerebral palsy (CP) using the Caregiver
      Priorities and Child Health Index of Life with Disabilities (CPCHILD((r)))
      questionnaire. METHODS: We assessed n = 34 patients (mean age: 10.2 years, SD:
      4.7 years; female: n = 16) with bilateral CP and Gross Motor Function
      Classification System (GMFCS) Level III-V using the CPCHILD((r)) questionnaire.
      Hip lateralisation was measured by Reimer's migration percentage (MP). RESULTS:
      There was an association between both, MP and GMFCS with CPCHILD((r)) total
      score. Stratified analyses did not suggest interaction of the association between
      MP and CPCHILD((r)) total score by GMFCS level. After adjustment for GMFCS level,
      we found a significant linear decrease of CPCHILD((r)) total score of -0.188
      points by 1% increment in MP. CONCLUSIONS: There was an association between MP
      and HRQL, which could not be explained by the GMFCS level.

PMID- 25057805
TI  - Granulocytic sarcoma of the cervix: Is hysterectomy necessary?

PMID- 25057806
TI  - Dietary selenium protect against redox-mediated immune suppression induced by
      methylmercury exposure.
AB  - The antagonism between selenium (Se) and mercury (Hg) has been widely recognized,
      however, the protective role of Se against methylmercury (MeHg) induced
      immunotoxicity and the underlying mechanism is still unclear. In the current
      study, MeHg exposure (0.01 mM via drinking water) significantly inhibited the
      lymphoproliferation and NK cells functions of the female Balb/c mice, while
      dietary Se supplementation (as Se-rich yeast) partly or fully recovered the
      observed immunotoxicity, indicating the protective role of Se against MeHg
      induced immune suppression in mice. Besides, MeHg exposure promoted the
      generation of the reactive oxygen species (ROS), reduced the levels of nonenzymic
      and enzymic antioxidants in target organs, while dietary Se administration
      significantly diminished the MeHg-induced oxidative stress and subsequent
      cellular dysfunctions (lipid peroxidation and protein oxidation). Two possible
      mechanisms of Se's protective effects were further revealed. Firstly, the
      reduction of mercury concentrations (less than 25%, modulated by Se
      supplementation) in the target organs might contribute, but not fully explain the
      alleviated immune suppression. Secondly and more importantly, Se could help to
      maintain/or elevate the activities of several key antioxidants, therefore protect
      the immune cells against MeHg-induced oxidative damage.

PMID- 25057807
TI  - Genetic and acute toxicological evaluation of an algal oil containing
      eicosapentaenoic acid (EPA) and palmitoleic acid.
AB  - Algal strains of Nannochloropsis sp. were developed, optimized, cultivated and
      harvested to produce a unique composition of algal oil ethyl esters (Algal-EE)
      that are naturally high in eicosapentaenoic acid (EPA, 23-30%) and palmitoleic
      acid (20-25%), and contain no docosahexaenoic acid (DHA). Algal-EE was evaluated
      for mutagenic activity (Ames bacterial reverse mutation, in vitro mammalian
      chromosome aberration, in vivo micronucleus test) and for acute oral toxicity in
      Sprague-Dawley rats. In the acute toxicity study, rats received a single oral
      gavaged dose of Algal-EE (2000 mg/kg body weight). Clinical observations were
      made for 14 days before sacrifice on Day 15. Macroscopic evaluation involved the
      examination of all organs in the cranial, thoracic, and abdominal cavities. Algal
      EE showed no evidence of mutagenicity, did not produce an increase in the
      frequency of structural chromosome aberrations, and did not cause an increase in
      the induction of micronucleated polychromatic erythrocytes. There were no
      macroscopic abnormalities. Algal-EE up to 2000 mg/kg body weight did not affect
      body weight, organ appearance or produce any toxic-related signs of morbidity.
      The acute median lethal dose (LD50) of Algal-EE was >2000 mg/kg body weight.
      Based on these assays, Algal-EE does not appear to have any genetic or acute oral
      toxicity.

PMID- 25057808
TI  - Ochratoxin A kinetics: a review of analytical methods and studies in rat model.
AB  - Ochratoxin A (OTA) is a thermostable mycotoxin that contaminates a great variety
      of foodstuffs. It is nephrotoxic in all of the mammalian species tested, the pig
      being the most sensitive one; among rodents, rats are the most susceptible to OTA
      carcinogenicity. Kinetics, by studying the absorption, distribution, metabolism
      and excretion of xenobiotics, is an important tool in the extrapolation of animal
      toxicity data for human risk assessment. The most important kinetic studies
      performed with OTA in rats are reviewed, together with the different methods used
      for OTA quantification in biological matrices. Twelve studies in Wistar, Sprague
      Dawley or F344 rats, using radiolabeled OTA or TLC, HPLC-FLD or LC/MS have been
      summarized. Very often methods validated for food have been directly applied to
      tissues. Strain, sex and age differences have been detected but the
      interpretation is difficult due to the different experimental conditions, and the
      connection of the several factors that may account for these differences. 

PMID- 25057809
TI  - Peripheral blood mononuclear cells as in vivo model for dietary intervention
      induced systemic oxidative stress.
AB  - Our aim was to assess the use of peripheral blood mononuclear cells (PBMC) as an
      in vivo cellular model to evaluate diet-induced changes in the oxidative stress
      status by analyzing the gene expression pattern of NADPH-oxidase subunits and
      antioxidant genes. A randomized, controlled trial assigned metabolic syndrome
      patients to 4 diets for 12 weeks each: (i) high-saturated fatty acid (HSFA), (ii)
      high-monounsaturated fatty acid, and (iii), (iv) two low-fat, high-complex
      carbohydrate diets supplemented with n-3 polyunsaturated fatty acids or placebo.
      A fat challenge reflecting the fatty acid composition as the original diets was
      conducted post-intervention. The mRNA levels of gp91(phox) (P<0.001), p22(phox)
      (P=0.005), p47(phox) (P=0.001) and p40(phox) (P<0.001) increased at 2h after the
      intake of the HSFA meal. The expression of SOD1, SOD2, GSR, GPx1, GPX4, TXN,
      TXNRD1 and Nrf2 increased after the HSFA meal (p<0.05). In contrast, the
      expression of these genes remained unaltered in response to the other dietary
      interventions. Our results suggest that the increased expression of antioxidant
      genes in PBMC seems to be due to the response to the postprandial oxidative
      stress generated mainly in adipose tissue after the consumption of an HSFA diet.

PMID- 25057812
TI  - An experimental and computational study to understand the lithium storage
      mechanism in molybdenum disulfide.
AB  - The lithium storage mechanism in molybdenum disulfide (MoS(2)) has been
      comprehensively investigated as the existing conversion-based storage mechanism
      is unable to explain the reason behind its high practical capacity, high
      polarization losses, and the change in the discharge profile after the 1(st)
      charge-discharge cycle. To resolve these issues and to gain a deeper
      understanding of MoS(2)-based Li-ion batteries, for the first time, we have
      studied the reaction mechanism of the MoS(2) anode using various experimental
      techniques such as XRD, Raman spectroscopy, electrochemical impedance
      spectroscopy, XANES, and EXAFS, as well as ab initio density functional theory
      based calculations. On the basis of the results presented here, and in line with
      some experimental findings, we find that the reaction of MoS(2) with Li is not as
      simple as with usual metal oxide based conversion reactions, but that the pathway
      of the conversion reaction changes after the first discharge process. In the
      first discharge process, lithiation is initiated by a limited intercalation
      process, followed by a conversion reaction that produces molybdenum nanoparticles
      (Mo) and lithium sulfide (Li(2)S). Whereas, unlike oxide-based conversion
      materials, MoS(2) does not transverse back during the delithiation process.
      Indeed, instead of MoS(2) formation, we identified the presence of polysulfur
      after the complete cycle. In consecutive cycles, polysulfur reacts with lithium
      and forms Li(2)S/Li(2)S(2), and this Li-S reaction is found to be highly
      reversible in nature and the only source of the high practical capacity observed
      in this electrode. To validate our experimental findings, an atomic scale ab
      initio computational study was also carried out, which likewise suggests that Li
      first intercalates between the MoS(2) layers but that after a certain
      concentration, it reacts with MoS(2) to form Li(2)S. The calculations also
      support the non-reversibility of the conversion reaction, by showing that Mo +
      Li(2)S formation is energetically more favorable than the re-formation of MoS(2)
      + Li.

PMID- 25057811
TI  - Molecular characterization of L class genome segments of a newly isolated turkey
      arthritis reovirus.
AB  - Seven strains of turkey arthritis reovirus (TARV) isolated from cases of turkey
      arthritis were characterized on the basis of their L class genome segment
      sequences, which were then compared with those of turkey enteric reovirus (TERV)
      and chicken reovirus (CRV). All three L class gene segments of TARVs and TERVs
      and their encoded proteins lambdaA, lambdaB, and lambdaC were similar in size to
      those of CRV reference strain S1133. The conserved motifs such as C2H2 zinc
      binding motif and conserved polymerase region were present in lambdaA and
      lambdaB, respectively. A conserved motif for ATP/GTP-binding site and an S
      adenosyl-l-methionine (SAM)-binding pocket for methyltransferase were observed in
      lambdaC protein of TARVs and TERVs with only one substitution as compared to that
      in CRV. We propose a new genotype classification system for avian reoviruses
      (ARVs) based on the nt identity cut-off value for each of the L class. Based on
      this new genotype classification, all ARVs were divided into six, seven and eight
      genotypes in L1, L2 and L3 genes, respectively. Interestingly TARVs and TERVs
      grouped with three CRVs (two arthritic strains from Taiwan and one enteritic
      strain from Japan) in genotype L1-I and formed a different genotypes (L2-I, L3-I)
      from CRVs in L2 and L3 genes. The maximum nucleotide divergence was observed in
      genotypes of L1 and L2 genes but less at amino acid level indicates mostly
      changes were synonymous type. Compared to L1 and L2 genes, the nonsynonymous
      changes were more in L3 gene. Point mutations and possible reassortments among
      TARVs, TERVs and CRVs were also observed. 

PMID- 25057813
TI  - A push-pull CORF model of a simple cell with antiphase inhibition improves SNR
      and contour detection.
AB  - We propose a computational model of a simple cell with push-pull inhibition, a
      property that is observed in many real simple cells. It is based on an existing
      model called Combination of Receptive Fields or CORF for brevity. A CORF model
      uses as afferent inputs the responses of model LGN cells with appropriately
      aligned center-surround receptive fields, and combines their output with a
      weighted geometric mean. The output of the proposed model simple cell with push
      pull inhibition, which we call push-pull CORF, is computed as the response of a
      CORF model cell that is selective for a stimulus with preferred orientation and
      preferred contrast minus a fraction of the response of a CORF model cell that
      responds to the same stimulus but of opposite contrast. We demonstrate that the
      proposed push-pull CORF model improves signal-to-noise ratio (SNR) and achieves
      further properties that are observed in real simple cells, namely separability of
      spatial frequency and orientation as well as contrast-dependent changes in
      spatial frequency tuning. We also demonstrate the effectiveness of the proposed
      push-pull CORF model in contour detection, which is believed to be the primary
      biological role of simple cells. We use the RuG (40 images) and Berkeley (500
      images) benchmark data sets of images with natural scenes and show that the
      proposed model outperforms, with very high statistical significance, the basic
      CORF model without inhibition, Gabor-based models with isotropic surround
      inhibition, and the Canny edge detector. The push-pull CORF model that we propose
      is a contribution to a better understanding of how visual information is
      processed in the brain as it provides the ability to reproduce a wider range of
      properties exhibited by real simple cells. As a result of push-pull inhibition a
      CORF model exhibits an improved SNR, which is the reason for a more effective
      contour detection. 

PMID- 25057814
TI  - An ARID domain-containing protein within nuclear bodies is required for sperm
      cell formation in Arabidopsis thaliana.
AB  - In plants, each male meiotic product undergoes mitosis, and then one of the
      resulting cells divides again, yielding a three-celled pollen grain comprised of
      a vegetative cell and two sperm cells. Several genes have been found to act in
      this process, and DUO1 (DUO POLLEN 1), a transcription factor, plays a key role
      in sperm cell formation by activating expression of several germline genes. But
      how DUO1 itself is activated and how sperm cell formation is initiated remain
      unknown. To expand our understanding of sperm cell formation, we characterized an
      ARID (AT-Rich Interacting Domain)-containing protein, ARID1, that is specifically
      required for sperm cell formation in Arabidopsis. ARID1 localizes within nuclear
      bodies that are transiently present in the generative cell from which sperm cells
      arise, coincident with the timing of DUO1 activation. An arid1 mutant and
      antisense arid1 plants had an increased incidence of pollen with only a single
      sperm-like cell and exhibited reduced fertility as well as reduced expression of
      DUO1. In vitro and in vivo evidence showed that ARID1 binds to the DUO1 promoter.
      Lastly, we found that ARID1 physically associates with histone deacetylase 8 and
      that histone acetylation, which in wild type is evident only in sperm, expanded
      to the vegetative cell nucleus in the arid1 mutant. This study identifies a novel
      component required for sperm cell formation in plants and uncovers a direct
      positive regulatory role of ARID1 on DUO1 through association with histone
      acetylation. 

PMID- 25057815
TI  - Seed rain and seed bank reveal that seed limitation strongly influences plant
      community assembly in grasslands.
AB  - Dispersal is an important factor in plant community assembly, but assembly
      studies seldom include information on actual dispersal into communities, i.e. the
      local propagule pool. The aim of this study was to determine which factors
      influence plant community assembly by focusing on two phases of the assembly
      process: the dispersal phase and the establishment phase. At 12 study sites in
      grazed ex-arable fields in Sweden the local plant community was determined and in
      a 100-m radius around the centre of each site, the regional species pool was
      measured. The local seed bank and the seed rain was explored to estimate the
      local propagule pool. Trait-based models were then applied to investigate if
      species traits (height, seed mass, clonal abilities, specific leaf area and
      dispersal method) and regional abundance influenced which species from the
      regional species pool, dispersed to the local community (dispersal phase) and
      which established (establishment phase). Filtering of species during the
      dispersal phase indicates the effect of seed limitation while filtering during
      the establishment phase indicates microsite limitation. On average 36% of the
      regional species pool dispersed to the local sites and of those 78% did
      establish. Species with enhanced dispersal abilities, e.g. higher regional
      abundance, smaller seeds and dispersed by cattle, were more likely to disperse to
      the sites than other species. At half the sites, dispersal was influenced by
      species height. Species establishment was however mainly unlinked to the traits
      included in this study. This study underlines the importance of seed limitation
      in local plant community assembly. It also suggests that without information on
      species dispersal into a site, it is difficult to distinguish between the
      influence of dispersal and establishment abilities, and thus seed and microsite
      limitation, as both can be linked to the same trait. 

PMID- 25057816
TI  - Cetacean vocal learning and communication.
AB  - The cetaceans are one of the few mammalian clades capable of vocal production
      learning. Evidence for this comes from synchronous changes in song patterns of
      baleen whales and experimental work on toothed whales in captivity. While baleen
      whales like many vocal learners use this skill in song displays that are involved
      in sexual selection, toothed whales use learned signals in individual recognition
      and the negotiation of social relationships. Experimental studies demonstrated
      that dolphins can use learned signals referentially. Studies on wild dolphins
      demonstrated how this skill appears to be useful in their own communication
      system, making them an interesting subject for comparative communication studies.

PMID- 25057817
TI  - Photovoltaic effect in an electrically tunable van der Waals heterojunction.
AB  - Semiconductor heterostructures form the cornerstone of many electronic and
      optoelectronic devices and are traditionally fabricated using epitaxial growth
      techniques. More recently, heterostructures have also been obtained by vertical
      stacking of two-dimensional crystals, such as graphene and related two
      dimensional materials. These layered designer materials are held together by van
      der Waals forces and contain atomically sharp interfaces. Here, we report on a
      type-II van der Waals heterojunction made of molybdenum disulfide and tungsten
      diselenide monolayers. The junction is electrically tunable, and under
      appropriate gate bias an atomically thin diode is realized. Upon optical
      illumination, charge transfer occurs across the planar interface and the device
      exhibits a photovoltaic effect. Advances in large-scale production of two
      dimensional crystals could thus lead to a new photovoltaic solar technology. 

PMID- 25057818
TI  - Hierarchical core-shell carbon nanofiber@ZnIn2S4 composites for enhanced hydrogen
      evolution performance.
AB  - Improvement of hydrogen evolution ability is an urgent task for developing
      advanced catalysts. As one of the promising visible-light photocatalysts, ZnIn2S4
      suffers from the ultrafast recombination of photoinduced charges, which limits
      its practical application for efficient solar water splitting. Herein, we
      reported a two-step method to prepare hierarchical core-shell carbon
      nanofiber@ZnIn2S4 composites. One-dimensional carbon nanofibers were first
      prepared by electrospinning and carbonization in N2. The subsequent solvothermal
      process led to the in situ growth of ZnIn2S4 nanosheets on the carbon nanofibers
      to fabricate hierarchical structure composites. The hierarchical core-shell
      configuration structure can help to form an intimate contact between the ZnIn2S4
      nanosheet shell and the carbon nanofiber backbone compared with the equivalent
      physical mixture and can facilitate the interfacial charge transfer driven by the
      excitation of ZnIn2S4 under visible-light irradiation. Meanwhile, the ultrathin
      ZnIn2S4 nanosheets were uniformly grown on the surface of the carbon nanofibers,
      which can avoid agglomeration of ZnIn2S4. These synergistic effects made this
      unique hierarchical structure composite exhibit a significantly higher visible
      light photocatalytic activity toward hydrogen evolution reaction compared with
      pure ZnIn2S4 or a physical mixture of ZnIn2S4 and carbon nanofibers in the
      absence of noble metal cocatalysts. 

PMID- 25057819
TI  - Quantifying a nonnotifiable disease in the United States: the National
      Amyotrophic Lateral Sclerosis Registry model.

PMID- 25057820
TI  - Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound
      infection.
AB  - Opportunistic infections caused by Pseudomonas aeruginosa can be acute or
      chronic. While acute infections often spread rapidly and can cause tissue damage
      and sepsis with high mortality rates, chronic infections can persist for weeks,
      months, or years in the face of intensive clinical intervention. Remarkably, this
      diverse infectious capability is not accompanied by extensive variation in
      genomic content, suggesting that the genetic capacity to be an acute or a chronic
      pathogen is present in most P. aeruginosa strains. To investigate the genetic
      requirements for acute and chronic pathogenesis in P. aeruginosa infections, we
      combined high-throughput sequencing-mediated transcriptome profiling (RNA-seq)
      and genome-wide insertion mutant fitness profiling (Tn-seq) to characterize gene
      expression and fitness determinants in murine models of burn and non-diabetic
      chronic wound infection. Generally we discovered that expression of a gene in
      vivo is not correlated with its importance for fitness, with the exception of
      metabolic genes. By combining metabolic models generated from in vivo gene
      expression data with mutant fitness profiles, we determined the nutritional
      requirements for colonization and persistence in these infections. Specifically,
      we found that long-chain fatty acids represent a major carbon source in both
      chronic and acute wounds, and P. aeruginosa must biosynthesize purines, several
      amino acids, and most cofactors during infection. In addition, we determined that
      P. aeruginosa requires chemotactic flagellar motility for fitness and virulence
      in acute burn wound infections, but not in non-diabetic chronic wound infections.
      Our results provide novel insight into the genetic requirements for acute and
      chronic P. aeruginosa wound infections and demonstrate the power of using both
      gene expression and fitness profiling for probing bacterial virulence. 

PMID- 25057821
TI  - Identification and characterization of microRNAs in small brown planthopper
      (Laodephax striatellus) by next-generation sequencing.
AB  - MicroRNAs (miRNAs) are endogenous non-coding small RNAs that regulate gene
      expression at the post-transcriptional level and are thought to play critical
      roles in many metabolic activities in eukaryotes. The small brown planthopper
      (Laodephax striatellus Fallen), one of the most destructive agricultural pests,
      causes great damage to crops including rice, wheat, and maize. However,
      information about the genome of L. striatellus is limited. In this study, a small
      RNA library was constructed from a mixed L. striatellus population and sequenced
      by Solexa sequencing technology. A total of 501 mature miRNAs were identified,
      including 227 conserved and 274 novel miRNAs belonging to 125 and 250 families,
      respectively. Sixty-nine conserved miRNAs that are included in 38 families are
      predicted to have an RNA secondary structure typically found in miRNAs. Many
      miRNAs were validated by stem-loop RT-PCR. Comparison with the miRNAs in 84
      animal species from miRBase showed that the conserved miRNA families we
      identified are highly conserved in the Arthropoda phylum. Furthermore, miRanda
      predicted 2701 target genes for 378 miRNAs, which could be categorized into 52
      functional groups annotated by gene ontology. The function of miRNA target genes
      was found to be very similar between conserved and novel miRNAs. This study of
      miRNAs in L. striatellus will provide new information and enhance the
      understanding of the role of miRNAs in the regulation of L. striatellus
      metabolism and development. 

PMID- 25057822
TI  - Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida
      albicans infection.
AB  - Delta-9-tetrahydrocannabinol (Delta9-THC), the psychoactive component of
      marijuana, is known to suppress the immune responses to bacterial, viral and
      protozoan infections, but its effects on fungal infections have not been studied.
      Therefore, we investigated the effects of chronic Delta9-THC treatment on mouse
      resistance to systemic Candida albicans (C. albicans) infection. To determine the
      outcome of chronic Delta9-THC treatment on primary, acute systemic candidiasis,
      c57BL/6 mice were given vehicle or Delta9-THC (16 mg/kg) in vehicle on days 1-4,
      8-11 and 15-18. On day 19, mice were infected with 5*10(5) C. albicans. We also
      determined the effect of chronic Delta9-THC (4-64 mg/kg) treatment on mice
      infected with a non-lethal dose of 7.5*10(4) C. albicans on day 2, followed by a
      higher challenge with 5*10(5) C. albicans on day 19. Mouse resistance to the
      infection was assessed by survival and tissue fungal load. Serum cytokine levels
      were determine to evaluate the immune responses. In the acute infection, chronic
      Delta9-THC treatment had no effect on mouse survival or tissue fungal load when
      compared to vehicle treated mice. However, Delta9-THC significantly suppressed IL
      12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated
      mice. In comparison, when mice were given a secondary yeast infection, Delta9-THC
      significantly decreased survival, increased tissue fungal burden and suppressed
      serum IFN-gamma and IL-12p40 levels compared to vehicle treated mice. The data
      showed that chronic Delta9-THC treatment decreased the efficacy of the memory
      immune response to candida infection, which correlated with a decrease in IFN
      gamma that was only observed after the secondary candida challenge.

PMID- 25057823
TI  - Resting states are resting traits--an FMRI study of sex differences and menstrual
      cycle effects in resting state cognitive control networks.
AB  - To what degree resting state fMRI is stable or susceptible to internal mind
      states of the individual is currently an issue of debate. To address this issue,
      the present study focuses on sex differences and investigates whether resting
      state fMRI is stable in men and women or changes within relative short-term
      periods (i.e., across the menstrual cycle). Due to the fact that we recently
      reported menstrual cycle effects on cognitive control based on data collected
      during the same sessions, the current study is particularly interested in fronto
      parietal resting state networks. Resting state fMRI was measured in sixteen women
      during three different cycle phases (menstrual, follicular, and luteal). Fifteen
      men underwent three sessions in corresponding time intervals. We used independent
      component analysis to identify four fronto-parietal networks. The results showed
      sex differences in two of these networks with women exhibiting higher functional
      connectivity in general, including the prefrontal cortex. Menstrual cycle effects
      on resting states were non-existent. It is concluded that sex differences in
      resting state fMRI might reflect sexual dimorphisms in the brain rather than
      transitory activating effects of sex hormones on the functional connectivity in
      the resting brain. 

PMID- 25057824
TI  - Mental health and related factors after the Great East Japan earthquake and
      tsunami.
AB  - Mental health is one of the most important issues facing disaster survivors. The
      purpose of this study is to determine the prevalence and correlates of mental
      health problems in survivors of the Great East Japan Earthquake and Tsunami at 6
      11 months after the disaster. The questionnaire and notification were sent to the
      survivors in three municipalities in the Tohoku area of the Northern part of
      Honshu, Japan's largest island, between September 2011 and February 2012.
      Questionnaires were sent to 12,772, 11,411, and 18,648 residents in the Yamada,
      Otsuchi, and Rikuzentakata municipalities, respectively. Residents were asked to
      bring the completed questionnaires to their health check-ups. A total of 11,124
      or (26.0%) of them underwent health check-ups, and 10,198 were enrolled. We
      excluded 179 for whom a K6 score was missing and two who were both 17 years of
      age, which left 10,025 study participants (3,934 male and 6,091 female, mean age
      61.0 years). K6 was used to measure mental health problems. The respondents were
      classified into moderate (5-12 of K6) and serious mental health problems (13+). A
      total of 42.6% of the respondents had moderate or serious mental health problems.
      Multivariate analysis showed that women were significantly associated with mental
      health problems. Other variables associated with mental health problems were:
      younger male, health complaints, severe economic status, relocations, and lack of
      a social network. An interaction effect of sex and economic status on severe
      mental health problems was statistically significant. Our findings suggest that
      mental health problems were prevalent in survivors of the Great East Japan
      Earthquake and Tsunami. For men and women, health complaints, severe economic
      status, relocations, and lack of social network may be important risk factors of
      poor mental health. For men, interventions focusing on economic support may be
      particularly useful in reducing mental health problems after the disaster. 

PMID- 25057839
TI  - Faces in the eye of the beholder: unique and stable eye scanning patterns of
      individual observers.
AB  - Eye scanning patterns while viewing pictures have provided valuable information
      in many domains of visual cognition. Such patterns are determined by the type of
      image viewed (e.g., faces, scenes) as well as the task individuals are asked to
      perform (e.g., visual search, memory). Here we show that another key factor that
      significantly influences eye scanning patterns but has been mostly overlooked is
      the individual observer. During face viewing, we found that individuals showed
      diverse scanning patterns that, in many cases, were inconsistent with the typical
      triangular shape pattern that is commonly observed when eye scanning patterns are
      averaged across individuals. These idiosyncratic eye scanning patterns were not
      random but highly stable even when examined 18 months later. Interestingly, these
      eye-tracking patterns were not predictive of behavioral performance. Such stable
      and unique scanning patterns may represent a specific behavioral trait/signature
      and be formed early in development, reflecting idiosyncratic strategies for
      performing visual recognition tasks.

PMID- 25057825
TI  - Cross-sectional study of the burden of vector-borne and soil-transmitted
      polyparasitism in rural communities of Coast Province, Kenya.
AB  - BACKGROUND: In coastal Kenya, infection of human populations by a variety of
      parasites often results in co-infection or poly-parasitism. These parasitic
      infections, separately and in conjunction, are a major cause of chronic clinical
      and sub-clinical human disease and exert a long-term toll on economic welfare of
      affected populations. Risk factors for these infections are often shared and
      overlap in space, resulting in interrelated patterns of transmission that need to
      be considered at different spatial scales. Integration of novel quantitative
      tools and qualitative approaches is needed to analyze transmission dynamics and
      design effective interventions. METHODOLOGY: Our study was focused on detecting
      spatial and demographic patterns of single- and co-infection in six villages in
      coastal Kenya. Individual and household level data were acquired using cross
      sectional, socio-economic, and entomological surveys. Generalized additive models
      (GAMs and GAMMs) were applied to determine risk factors for infection and co
      infections. Spatial analysis techniques were used to detect local clusters of
      single and multiple infections. PRINCIPAL FINDINGS: Of the 5,713 tested
      individuals, more than 50% were infected with at least one parasite and nearly
      20% showed co-infections. Infections with Schistosoma haematobium (26.0%) and
      hookworm (21.4%) were most common, as was co-infection by both (6.3%). Single and
      co-infections shared similar environmental and socio-demographic risk factors.
      The prevalence of single and multiple infections was heterogeneous among and
      within communities. Clusters of single and co-infections were detected in each
      village, often spatially overlapped, and were associated with lower SES and
      household crowding. CONCLUSION: Parasitic infections and co-infections are
      widespread in coastal Kenya, and their distributions are heterogeneous across
      landscapes, but inter-related. We highlighted how shared risk factors are
      associated with high prevalence of single infections and can result in spatial
      clustering of co-infections. Spatial heterogeneity and synergistic risk factors
      for polyparasitism need to be considered when designing surveillance and
      intervention strategies.

PMID- 25057840
TI  - Alterations in the functional connectivity of frontal lobe networks preceding
      emergence delirium in children.
AB  - BACKGROUND: This study aimed to characterize the electroencephalogram in children
      who emerged with emergence delirium (ED) compared with children without ED using
      methods that involved the assessment of cortical functional connectivity.
      METHODS: Children aged 5 to 15 yr had multichannel electroencephalographic
      recordings during induction and emergence from anesthesia during minor surgical
      procedures. Of these, five children displayed ED after sevoflurane anesthesia.
      Measures of cortical functional connectivity previously used to evaluate
      anesthetic action in adults were compared between ED and age-, sex-, and
      anesthetic-matched non-ED children during emergence from anesthesia. RESULTS: At
      the termination of sevoflurane anesthesia, the electroencephalogram in both ED
      and control patients showed delta frequency slowing and frontally dominant alpha
      activity, followed by a prolonged state with low-voltage, fast frequency activity
      (referred to as an indeterminate state). In children with ED, arousal with
      delirious behavior and a variety of electroencephalogram patterns occurred during
      the indeterminate state, before the appearance of normal wake or sleep patterns.
      The electroencephalogram in children without ED progressed from the indeterminate
      state to classifiable sleep or drowsy states, before peaceful awakening.
      Statistically significant differences in frontal lobe functional connectivity
      were identified between children with ED and non-ED. CONCLUSIONS: ED is
      associated with arousal from an indeterminate state before the onset of sleep
      like electroencephalogram patterns. Increased frontal lobe cortical functional
      connectivity observed in ED, immediately after the termination of sevoflurane
      anesthesia, will have important implications for the development of methods to
      predict ED, the design of preventative strategies, and efforts to better
      understand its pathophysiology.

PMID- 25057842
TI  - Case scenario: power of positive end-expiratory pressure: use of esophageal
      manometry to illustrate pulmonary physiology in an obese patient.

PMID- 25057843
TI  - Selective infraclavicular brachial plexus phenol injection for the relief of
      cancer pain.

PMID- 25057841
TI  - Distinctive recruitment of endogenous sleep-promoting neurons by volatile
      anesthetics and a nonimmobilizer.
AB  - BACKGROUND: Numerous studies demonstrate that anesthetic-induced unconsciousness
      is accompanied by activation of hypothalamic sleep-promoting neurons, which
      occurs through both pre- and postsynaptic mechanisms. However, the correlation
      between drug exposure, neuronal activation, and onset of hypnosis remains
      incompletely understood. Moreover, the degree to which anesthetics activate both
      endogenous populations of gamma-aminobutyric acid (GABA)ergic sleep-promoting
      neurons within the ventrolateral preoptic (VLPO) and median preoptic nuclei
      remains unknown. METHODS: Mice were exposed to oxygen, hypnotic doses of
      isoflurane or halothane, or 1,2-dichlorohexafluorocyclobutane (F6), a
      nonimmobilizer. Hypothalamic brain slices prepared from anesthetic-naive mice
      were also exposed to oxygen, volatile anesthetics, or F6 ex vivo, both in the
      presence and absence of tetrodotoxin. Double-label immunohistochemistry was
      performed to quantify the number of c-Fos-immunoreactive nuclei in the GABAergic
      subpopulation of neurons in the VLPO and the median preoptic areas to test the
      hypothesis that volatile anesthetics, but not nonimmobilizers, activate sleep
      promoting neurons in both nuclei. RESULTS: In vivo exposure to isoflurane and
      halothane doubled the fraction of active, c-Fos-expressing GABAergic neurons in
      the VLPO, whereas F6 failed to affect VLPO c-Fos expression. Both in the presence
      and absence of tetrodotoxin, isoflurane dose-dependently increased c-Fos
      expression in GABAergic neurons ex vivo, whereas F6 failed to alter expression.
      In GABAergic neurons of the median preoptic area, c-Fos expression increased with
      isoflurane and F6, but not with halothane exposure. CONCLUSIONS: Anesthetic
      unconsciousness is not accompanied by global activation of all putative sleep
      promoting neurons. However, within the VLPO hypnotic doses of volatile
      anesthetics, but not nonimmobilizers, activate putative sleep-promoting neurons,
      correlating with the appearance of the hypnotic state.

PMID- 25057844
TI  - Images in Anesthesiology: Dobutamine-induced Intraventricular Obstruction: A
      "Dagger" to the Anesthetized Heart?

PMID- 25057845
TI  - High-intensity interval training on an aquatic treadmill in adults with
      osteoarthritis: effect on pain, balance, function, and mobility.
AB  - Although aquatic exercise is considered a potentially effective treatment
      intervention for people with osteoarthritis (OA), previous research has focused
      primarily on calisthenics in a shallow pool with the inherent limitations on
      regulating exercise intensity. The purpose of this study was to quantify the
      efficacy of a 6-week aquatic treadmill exercise program on measures of pain,
      balance, function, and mobility. Eighteen participants (age = 64.5 +/- 10.2
      years) with knee OA completed a non-exercise control period followed by a 6-week
      exercise period. Outcome measures included visual analog scales for pain,
      posturography for balance, sit-to-stand test for function, and a 10-m walk test
      for mobility. The exercise protocol included balance training and high-intensity
      interval training (HIT) in an aquatic treadmill using water jets to destabilize
      while standing and achieve high ratings of perceived exertion (14-19) while
      walking. In comparison with pretests, participants displayed reduced joint pain
      (pre = 50.3 +/- 24.8 mm vs. post = 15.8 +/- 10.6 mm), improved balance
      (equilibrium pre = 66.6 +/- 11.0 vs. post = 73.5 +/- 7.1), function (rising index
      pre = 0.49 +/- 0.19% vs. post = 0.33 +/- 0.11%), and mobility (walk pre = 8.6 +/-
      1.4 s vs. post = 7.8 +/- 1.1 s) after participating in the exercise protocol (p =
      0.03-0.001). The same benefits were not observed after the non-exercise control
      period. Adherence to the exercise protocol was exceptional and no participants
      reported adverse effects, suggesting that aquatic treadmill exercise that
      incorporates balance and HIT training was well tolerated by patients with OA and
      may be effective at managing symptoms of OA.

PMID- 25057846
TI  - Could biochemical liver profile help to assess metabolic response to aerobic
      effort in athletes?
AB  - Monitoring and optimizing the effectiveness of training course require wide
      analyses of athletes' blood parameter changes. The aim of this study was to
      evaluate the usefulness of biochemical liver profile to assess the metabolic
      response to semi-long-distance outdoor run in football players. Sixteen football
      players run outdoor for 60 minutes to achieve aerobic metabolism. Plasma activity
      of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma
      glutamyltransferase (GGT) and plasma levels of total and direct bilirubin were
      determined in samples obtained before exercise test (pre-exercise) and
      immediately after the run (post-exercise). Mean AST plasma activity (U.L-1)
      before/after the exercise, respectively, was 78.3/228.3 in women and 76.5/56.2 in
      men. Mean ALT plasma activity (U.L-1) before/after the exercise, respectively,
      was 27.5/59.1 in women and 36.2/35.3 in men. Mean GGT plasma activity (U.L-1)
      before/after the exercise, respectively, was 39.3/76.6 in women and 44.7/71.2 in
      men. Plasma levels of total and direct bilirubin were similar before and after
      the run regardless of the gender. Statistical significance of the differences
      between results obtained pre- and post-exercise occurred in women (p = 0.0212 for
      AST; p = 0.0320 for ALT; p = 0.0067 for GGT, respectively). The training
      monitoring in athletes should be performed using measurements of performance and
      biological or physiological parameters. It was found that AST, ALT, and GGT
      activities could be a valuable tool to assess the metabolic response in high
      level fitness female athletes. Therefore, monitoring of those well-known
      diagnostic markers could prevent the trainee from harmful overtraining.

PMID- 25057847
TI  - Throwing performance and test-retest reliability in Olympic female water polo
      players.
AB  - Shooting performance is critical to successful water polo performance, requiring
      high levels of speed and accuracy. However, shooting speed and accuracy
      performance of elite female water polo players has not been described in detail
      nor has the reliability of accuracy measures been reported. Consequently, the aim
      of this study was to describe shooting performance in elite female water polo
      players and compare the test-retest reliability of the currently available
      accuracy measures. Ten Olympic female water polo players were tested on 3
      occasions before Olympic competition for maximal throwing speed and accuracy
      (total error and hit percentage) toward various target locations, with and
      without a goalkeeper (GK) present. The current participants (all Olympic
      athletes) achieved higher speeds (16.8 m.s-1), higher hit percentages (45.3%) of
      a 20-cm sniper net target, and lower errors (20.7 cm) than any other female water
      polo players investigated previously. Performance was similar across the
      different target locations; however, both speed (15.2 vs. 14.8 m.s-1; p <= 0.05)
      and accuracy (50.2 vs. 37.7%; p <= 0.05) were reduced in the presence of a GK.
      Speed and total error was similar across the 3 testing sessions; however, hit
      percentage was statistically significantly higher in the final session (58.8% vs.
      40.4 and 36.4%). Maximal throwing speed showed high levels of test-retest
      reliability (0.96). Total error (intraclass correlation [ICC] = 0.79) had
      slightly greater reliability than hit percentage (ICC = 0.73) overall. Hit
      percentage (ICC = 0.82) showed slightly greater reliability than total error (ICC
      = 0.72) without a GK present, whereas total error (ICC = 0.79) showed much
      greater reliability than hit percentage (ICC = 0.34) when a GK was present. This
      study benchmarks the high degree of throwing speed and accuracy required at the
      Olympic level in female water polo players. Although resource intensive, total
      error is a reliable measure of accuracy that allows for the nature of error to be
      described in detail, providing a great level of insight into performance. Hit
      percentage, while easier to obtain, should only be used when a GK is not present
      and in situations where describing the nature of error does not add value to
      coaching practices.

PMID- 25057848
TI  - Zaprinast and rolipram enhances spatial and emotional memory in the elevated plus
      maze and passive avoidance tests and diminishes exploratory activity in naive
      mice.
AB  - BACKGROUND: Phosphodiesterase (PDE) inhibitors in the central nervous system have
      been shown to stimulate neuronal functions and increase neurogenesis in Alzheimer
      disease (AD) patients. MATERIAL/METHODS: The aim of this study was to investigate
      the effects of zaprinast, a PDE5 inhibitor, and rolipram, a PDE4 inhibitor, on
      learning and memory in elevated plus maze (EPM) and passive avoidance (PA) tests
      in naive mice. Male Balb-c mice received short-term treatment with zaprinast (3
      and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) before the acquisition trial of
      the EPM and PA tests. The exploratory activity of the animals was also
      investigated in the Hughes box test. RESULTS: Both zaprinast (10 mg/kg) and
      rolipram (0.1 mg/kg) significantly decreased second-day latency compared to the
      control group in the EPM test, while only rolipram (0.1 mg/kg) significantly
      increased second-day latency in the PA test. Both zaprinast (10 mg/kg) and
      rolipram (0.1 mg/kg) significantly decreased the number of entries to new areas
      and time spent in new areas in the Hughes box test. CONCLUSIONS: Our study
      revealed that both zaprinast and rolipram enhanced spatial memory in EPM, while
      rolipram seemed to have more emotional memory-enhancing effects in the PA test
      compared to zaprinast. Both zaprinast and rolipram diminished exploratory
      activity in the Hughes box test, which can be attributed to the drugs' anxiogenic
      effects.

PMID- 25057849
TI  - Structural determination of Bi-doped magnetite multifunctional nanoparticles for
      contrast imaging.
AB  - To determine with precision how Bi atoms are distributed in Bi-doped iron oxide
      nanoparticles their structural characterization has been carried out by X-ray
      absorption spectroscopy (XAS) recorded at the K edge of Fe and at the L3 edge of
      Bi. The inorganic nanoparticles are nominally hybrid structures integrating an
      iron oxide core and a bismuth oxide shell. Fe K-edge XAS indicates the formation
      of a structurally ordered, non-stoichiometric magnetite (Fe3-deltaO4) phase for
      all the nanoparticles. The XAS spectra show that, in the samples synthesized by
      precipitation in aqueous media and laser pyrolysis, the Bi atoms neither enter
      into the iron oxide spinel lattice nor form any other mixed Bi-Fe oxides. No
      modification of the local structure around the Fe atoms induced by the Bi atoms
      is observed at the Fe K edge. In addition, contrary to expectations, our results
      indicate that the Bi atoms do not form a well-defined Bi oxide structure. The XAS
      study at the Bi L3 edge indicates that the environment around Bi atoms is highly
      disordered and only a first oxygen coordination shell is observed. Indefinite
      [BiO6-x(OH)x] units (isolated or aggregated forming tiny amorphous clusters)
      bonded through hydroxyl bridges to the nanoparticle, rather than a well defined
      Bi2O3 shell, surround the nanoparticle. On the other hand, the XAS study
      indicates that, in the samples synthesized by thermal decomposition, the Bi atoms
      are embedded in a longer range ordered structure showing the first and second
      neighbors. 

PMID- 25057850
TI  - The origin of high electrolyte-electrode interfacial resistances in lithium cells
      containing garnet type solid electrolytes.
AB  - Dense LLZO (Al-substituted Li7La3Zr2O12) pellets were processed in controlled
      atmospheres to investigate the relationships between the surface chemistry and
      interfacial behavior in lithium cells. Laser induced breakdown spectroscopy
      (LIBS), scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman
      spectroscopy, synchrotron X-ray photoelectron spectroscopy (XPS) and soft X-ray
      absorption spectroscopy (XAS) studies revealed that Li2CO3 was formed on the
      surface when LLZO pellets were exposed to air. The distribution and thickness of
      the Li2CO3 layer were estimated by a combination of bulk and surface sensitive
      techniques with various probing depths. First-principles thermodynamic
      calculations confirmed that LLZO has an energetic preference to form Li2CO3 in
      air. Exposure to air and the subsequent formation of Li2CO3 at the LLZO surface
      is the source of the high interfacial impedances observed in cells with lithium
      electrodes. Surface polishing can effectively remove Li2CO3 and dramatically
      improve the interfacial properties. Polished samples in lithium cells had an area
      specific resistance (ASR) of only 109 Omega cm(2) for the LLZO/Li interface, the
      lowest reported value for Al-substituted LLZO. Galvanostatic cycling results
      obtained from lithium symmetrical cells also suggest that the quality of the
      LLZO/lithium interface has a significant impact on the device lifetime. 

PMID- 25057851
TI  - Membrane analysis with amphiphilic carbon dots.
AB  - Newly-synthesized amphiphilic carbon dots were used for spectroscopic analysis
      and multicolour microscopic imaging of membranes and live cells. We show that
      Forster resonance energy transfer (FRET) occurred from the amphiphilic carbon
      dots to different membrane-associated fluorescence acceptors. The amphiphilic
      carbon dots enabled imaging of membrane disruption by the beta-amyloid peptide. 

PMID- 25057853
TI  - Collective behaviour without collective order in wild swarms of midges.
AB  - Collective behaviour is a widespread phenomenon in biology, cutting through a
      huge span of scales, from cell colonies up to bird flocks and fish schools. The
      most prominent trait of collective behaviour is the emergence of global order:
      individuals synchronize their states, giving the stunning impression that the
      group behaves as one. In many biological systems, though, it is unclear whether
      global order is present. A paradigmatic case is that of insect swarms, whose
      erratic movements seem to suggest that group formation is a mere epiphenomenon of
      the independent interaction of each individual with an external landmark. In
      these cases, whether or not the group behaves truly collectively is debated.
      Here, we experimentally study swarms of midges in the field and measure how much
      the change of direction of one midge affects that of other individuals. We
      discover that, despite the lack of collective order, swarms display very strong
      correlations, totally incompatible with models of non-interacting particles. We
      find that correlation increases sharply with the swarm's density, indicating that
      the interaction between midges is based on a metric perception mechanism. By
      means of numerical simulations we demonstrate that such growing correlation is
      typical of a system close to an ordering transition. Our findings suggest that
      correlation, rather than order, is the true hallmark of collective behaviour in
      biological systems. 

PMID- 25057852
TI  - Integrative genomic and transcriptomic analysis identified candidate genes
      implicated in the pathogenesis of hepatosplenic T-cell lymphoma.
AB  - Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically
      characterized by isochromosome 7q [i(7)(q10)], of which the molecular
      consequences remain unknown. We report here results of an integrative genomic and
      transcriptomic (expression microarray and RNA-sequencing) study of six i(7)(q10)
      positive HSTL cases, including HSTL-derived cell line (DERL-2), and three cases
      with ring 7 [r(7)], the recently identified rare variant aberration. Using high
      resolution array CGH, we profiled all cases and mapped the common deleted region
      (CDR) at 7p22.1p14.1 (34.88 Mb; 3506316-38406226 bp) and the common gained region
      (CGR) at 7q22.11q31.1 (38.77 Mb; 86259620-124892276 bp). Interestingly, CDR spans
      a smaller region of 13 Mb (86259620-99271246 bp) constantly amplified in cases
      with r(7). In addition, we found that TCRG (7p14.1) and TCRB (7q32) are involved
      in formation of r(7), which seems to be a byproduct of illegitimate somatic
      rearrangement of both loci. Further transcriptomic analysis has not identified
      any CDR-related candidate tumor suppressor gene. Instead, loss of 7p22.1p14.1
      correlated with an enhanced expression of CHN2 (7p14.1) and the encoded beta2
      chimerin. Gain and amplification of 7q22.11q31.1 are associated with an increased
      expression of several genes postulated to be implicated in cancer, including
      RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did
      not identify any disease-defining mutation or gene fusion. Thus, chromosome 7
      imbalances remain the only driver events detected in this tumor. We hypothesize
      that the Delta7p22.1p14.1-associated enhanced expression of CHN2/beta2-chimerin
      leads to downmodulation of the NFAT pathway and a proliferative response, while
      upregulation of the CGR-related genes provides growth advantage for neoplastic
      deltagammaT-cells and underlies their intrinsic chemoresistance. Finally, our
      study confirms the previously described gene expression profile of HSTL and
      identifies a set of 24 genes, including three located on chromosome 7 (CHN2,
      ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies. 

PMID- 25057854
TI  - Quercetin, luteolin, and epigallocatechin gallate promote glucose disposal in
      adipocytes with regulation of AMP-activated kinase and/or sirtuin 1 activity.
AB  - Quercetin, luteolin, and epigallocatechin gallate are flavonoids abundant in
      edible and medicinal plants with beneficial effects on glucose homeostasis. This
      study explored the action of these flavonoids on glucose disposal in adipocytes.
      Quercetin, luteolin, and epigallocatechin gallate enhanced glucose consumption
      with the positive regulation of AMP-activated kinase phosphorylation, and the AMP
      activated kinase inhibitor compound C abolished their effects on glucose
      consumption. Luteolin and epigallocatechin gallate, but not quercetin, increased
      sirtuin 1 abundance, and their regulation of glucose consumption was also
      attenuated by co-treatment with sirtuin 1 inhibitor nicotinamide. Quercetin,
      luteolin, and epigallocatechin gallate suppressed nuclear factor-kappaB
      activation by inhibition of p65 phosphorylation with beneficial regulation of
      adipokine expression, whereas these actions were diminished by coincubation with
      compound C. The sirtuin 1 inhibitor nicotinamide attenuated the effects of
      luteolin and EGCG on p65 phosphorylation and adipokine expression without any
      influence on the activity of quercetin. Results of Western blot and fluorescence
      microscopy also showed that quercetin, luteolin, and epigallocatechin gallate
      increased Akt substrate of 160 kDa phosphorylation and promoted 2-deoxy-D-glucose
      uptake by adipocytes under basal and inflammatory conditions. These findings
      suggested that quercetin, luteolin, and epigallocatechin gallate inhibited
      inflammation and promoted glucose disposal in adipocytes with the regulation of
      AMP-activated kinase and/or sirtuin 1. 

PMID- 25057856
TI  - B cell receptor signaling-based index as a biomarker for the loss of peripheral
      immune tolerance in autoreactive B cells in rheumatoid arthritis.
AB  - This study examines the loss of peripherally induced B cell immune tolerance in
      Rheumatoid arthritis (RA) and establishes a novel signaling-based measure of
      activation in a subset of autoreactive B cells--the Induced tolerance status
      index (ITSI). Naturally occurring naive autoreactive B cells can escape the
      "classical" tolerogenic mechanisms of clonal deletion and receptor editing, but
      remain peripherally tolerized through B cell receptor (BCR) signaling inhibition
      (postdevelopmental "receptor tuning" or anergy). ITSI is a statistical index that
      numerically determines the level of homology between activation patterns of BCR
      signaling intermediaries in B cells that are either tolerized or activated by
      auto antigen exposure, and thus quantifies the level of peripheral immune
      tolerance. The index is based on the logistic regression analysis of
      phosphorylation levels in a panel of BCR signaling proteins. Our results
      demonstrate a new approach to identifying autoreactive B cells based on their BCR
      signaling features.

PMID- 25057857
TI  - Rare and uncommon genetic variants may hold key to the 'missing heritability' in
      glioma.

PMID- 25057858
TI  - The Hippo signaling pathway and translational opportunities for brain cancers.

PMID- 25057855
TI  - Proteome-wide analysis of human disease mutations in short linear motifs:
      neglected players in cancer?
AB  - Disease mutations are traditionally thought to impair protein functionality by
      disrupting the folded globular structure of proteins. However, 22% of human
      disease mutations occur in natively unstructured segments of proteins known as
      intrinsically disordered regions (IDRs). This therefore implicates defective IDR
      functionality in various human diseases including cancer. The functionality of
      IDRs is partly attributable to short linear motifs (SLiMs), but it remains an
      open question how much defects in SLiMs contribute to human diseases. A proteome
      wide comparison of the distribution of missense mutations from disease and non
      disease mutation datasets revealed that, in IDRs, disease mutations are more
      likely to occur within SLiMs than neutral missense mutations. Moreover, compared
      to neutral missense mutations, disease mutations more frequently impact
      functionally important residues of SLiMs, cause changes in the physicochemical
      properties of SLiMs, and disrupt more SLiM-mediated interactions. Analysis of
      these mutations resulted in a comprehensive list of experimentally validated or
      predicted SLiMs disrupted in disease. Furthermore, this in-depth analysis
      suggests that 'prostate cancer pathway' is particularly enriched for proteins
      with disease-related SLiMs. The contribution of mutations in SLiMs to disease may
      currently appear small when compared to mutations in globular domains. However,
      our analysis of mutations in predicted SLiMs suggests that this contribution
      might be more substantial. Therefore, when analysing the functional impact of
      mutations on proteins, SLiMs in proteins should not be neglected. Our results
      suggest that an increased focus on SLiMs in the coming decades will improve our
      understanding of human diseases and aid in the development of targeted
      treatments. 

PMID- 25057861
TI  - When should proton radiation therapy be used to treat brain tumors?

PMID- 25057862
TI  - Neuro-oncology: a selected review of ASCO 2012 abstracts.
AB  - The American Society of Clinical Oncology (ASCO), the largest clinical oncology
      meeting in the USA, meets annually and reproducibly provides an exciting forum to
      present new cancer clinical trials and research data. The ASCO 2012 CNS tumors
      section comprised 3 days of presentations and over 130 abstracts, providing an
      overview of neuro-oncology, including both metastatic diseases of the CNS and
      primary brain tumors. This brief review attempts to highlight select abstracts
      presented at this year's meeting in an organized manner that will provide a
      portrait of a large and multifaceted meeting. 

PMID- 25057863
TI  - Image guidance in malignant gliomas: a focused strategy.
AB  - The standard of care for malignant gliomas is maximal surgical cytoreduction
      followed by concurrent chemoradiation and adjuvant chemotherapy with
      temozolomide. Chemotherapy adds a modest improvement in overall survival.
      Unfortunately, tumor recurrence is the rule and typically occurs at the initial
      site of disease. Salvage reirradiation may be a useful approach in selected
      patients with recurrent glioblastoma. Image-guided technology coupled with highly
      conformal treatment planning techniques have allowed the safe delivery of high
      dose radiotherapy in the setting of tumor recurrence. Defining the optimal
      combination of hypofractionated stereotactic radiotherapy with chemotherapy is
      under investigation. In this perspective, we examine the role of image guidance
      in malignant gliomas.

PMID- 25057864
TI  - Pediatric diffuse intrinsic pontine glioma: can optimism replace pessimism?
AB  - Pediatric diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis that has
      not seen a change in outcome despite multiple clinical trials. Possible reasons
      for failure to make progress in this aggressive childhood brain tumor include:
      poor understanding of the underlying molecular biology due to lack of access to
      tumor material; absence of accurate and relevant DIPG preclinical models for drug
      development; ill-defined therapeutic targets for novel agents; and inadequate
      drug delivery to the brainstem. This review will demonstrate that systematic
      studies to identify solutions for each of these barriers is starting to deliver
      progress that can turn pessimism to optimism in DIPG.

PMID- 25057865
TI  - Diffusion-weighted MRI in neuro-oncology.
AB  - Diffusion-weighted MRI (DW-MRI) provides image contrast dependent on the
      molecular movement of water. It has been most widely used in the diagnosis of
      cytotoxic edema secondary to acute cerebral ischemia, but has also proven useful
      in assessing tumor cellularity and grade, abscess formation, cysts and various
      forms of white matter disorders. Furthermore, DW-MRI is used to generate maps of
      subcortical white matter tracts and their relationship to structural brain
      lesions that may serve for preoperative planning and intraoperative guidance. We
      provide a comprehensive review of current practical applications of DW-MRI in the
      diagnosis and treatment of primary brain tumors, metastases and nonmetastatic
      neurologic complications of cancer. A detailed description of diffusion tensor
      imaging is beyond the scope of this review. We performed a comprehensive search
      of the PubMed database of the USA National Library of Medicine with use of
      various combinations of the following search terms: diffusion-weighted imaging,
      apparent diffusion coefficient, diffusion tensor imaging, diffusion tensor,
      brain, tumor, glioblastoma, lymphoma, primary CNS lymphoma, stroke, cancer,
      abscess, leukoencephalopathy, methotrexate, fluorouracil, capecitabine. We
      identified original articles and well-documented case reports of DW-MRI
      applications in patients with primary brain neoplasms, metastases and
      nonmetastatic neurologic complications that we judged to be of high impact on the
      field. We largely selected publications from the past 10 years, but did not
      exclude commonly referenced and highly regarded older publications. We also
      searched the reference lists of articles identified by this search strategy and
      selected those we judged relevant. Review articles are cited to provide readers
      with more details and more references than can be covered here.

PMID- 25057866
TI  - Surgical management of high-grade glioma: a standard of care.
AB  - Neurosurgical oncology for intrinsic glioma is evolving rapidly. It must be
      patient-centered, consultant-led and research-orientated. The value of specialist
      neurosurgical engagement is becoming more widely recognized. Detailed evaluation
      tailored to each patient is essential before the surgical admission, in
      conjunction with clinical oncology input. Medical optimization, collation of
      magnetic resonance datasets for preoperative planning and providing an informed
      explanation of the proposed management and its alternatives are all part of the
      neurosurgeon's remit. Meticulous microsurgical technique during surgery utilizing
      modern neuronavigation and physiological monitoring are integral components of
      the specialist armamentarium. A clear understanding of the rationale for surgical
      intervention, including its place alongside radiotherapy and chemotherapy,
      informs surgical decision-making. Recognition and understanding of these issues
      are driving the evolution of neurosurgical management of high-grade glioma. New
      challenges are emerging and need to be critically evaluated in robustly designed
      clinical trials.

PMID- 25057867
TI  - Treating glioblastoma in the elderly.
AB  - The incidence of glioblastoma (GBM) is increasing among the elderly, who now
      account for up to half of all the adult cases of GBM. This trend has resulted in
      the recent development of clinical research specifically dedicated to this
      fragile population. Some studies have investigated surgical resection,
      radiotherapy and chemotherapy with temozolomide, and ongoing research is
      currently addressing the use of combined radiochemotherapy in this population.
      Although older patients with GBM have a significantly worse life expectancy
      compared with their younger counterparts, etiologic treatments should not be
      withheld from these patients solely because of their age. On the contrary,
      results from prospective studies suggest that active care of these patients has a
      significant positive impact on survival without affecting quality of life or
      cognition. To optimize both symptomatic and etiologic treatment, neuro-oncology
      multidisciplinary teams must take into account performance and cognitive status,
      the resectability of the tumor, and associated comorbidities.

PMID- 25057869
TI  - A 1st-trimester combined screening test in pregnant women of advanced maternal
      age in a Chinese population.
AB  - The purpose of this study was to evaluate the performance of the 1st-trimester
      combined screening test for trisomy 21 in different maternal age groups in a
      Chinese population. In this retrospective study, data on the 1st-trimester
      combined screening test (maternal age, fetal nuchal translucency, free beta-human
      chorionic gonadotrophin, pregnancy-associated plasma protein-A) were analysed.
      The study population of 17,556 pregnant women was subdivided into three groups
      according to maternal age: 16,113 were < 35 years of age; 1,228 were 35-39 years
      of age; and 215 were >= 40 years of age. The detection and false-positive rates
      of the 1st-trimester screening test for trisomy 21 or trisomy 18 in the three
      groups of women were 89.5 and 1.7%; 90.9 and 6.8%; and 100 and 22.3%,
      respectively. With increasing maternal age, the odds of being affected given a
      positive result (OAPR) were increased. The balance between the detection rate and
      false-positive rate of the 1st-trimester combined screening test is more
      favourable in women < 36 years with comparable OAPR. Although the false-positive
      rate increases with increasing maternal age, the performance of the 1st-trimester
      combined screening test in women >= 35 years is more effective than screening
      based on maternal age alone.

PMID- 25057870
TI  - Modest CaV1.342-selective inhibition by compound 8 is beta-subunit dependent.
AB  - Two voltage-gated calcium channel subtypes-CaV1.2 and CaV1.3-underlie the major L
      type Ca(2+) currents in the mammalian central nervous system. Owing to their high
      sequence homology, the two channel subtypes share similar pharmacological
      properties, and at high doses classic calcium channel blockers, such as
      dihydropyridines, phenylalkylamines and benzothiazepines, do not discriminate
      between the two channel subtypes. Recent progress in treating Parkinson's disease
      (PD) was marked by the discovery of synthetic compound 8, which was reported to
      be a highly selective inhibitor of the CaV1.3 L-type calcium channels (LTCC).
      However, despite a previously reported IC50 of ~24 MUM, in our hands inhibition
      of the full-length CaV1.342 by compound 8 at 50 MUM reaches a maximum of 45%.
      Moreover, we find that the selectivity of compound 8 towards CaV1.3 relative to
      CaV1.2B15 channels is greatly influenced by the beta-subunit type and its splice
      isoform variants.

PMID- 25057871
TI  - Healthcare resource utilization for recurrent Clostridium difficile infection in
      a large university hospital in Houston, Texas.
AB  - BACKGROUND: There are limited data examining healthcare resource utilization in
      patients with recurrent Clostridium difficile infection (CDI). METHODS: Patients
      with CDI at a tertiary-care hospital in Houston, TX, were prospectively enrolled
      into an observational cohort study. Recurrence was assessed via follow-up phone
      calls. Patients with one or more recurrence were included in this study. The
      location at which healthcare was obtained by patients with recurrent CDI was
      identified along with hospital length of stay. CDI-attributable readmissions,
      defined as a positive toxin test within 48 hours of admission and a primary CDI
      diagnosis, were also assessed. RESULTS: 372 primary cases of CDI were identified
      of whom 64 (17.2%) experienced at least one CDI recurrence. Twelve of 64 patients
      experienced 18 further episodes of CDI recurrence. Of these 64 patients, 33
      (50.8%) patients with recurrent CDI were readmitted of which 6 (18.2%) required
      ICU care, 29 (45.3%) had outpatient care only, and 2 (3.1%) had an ED visit.
      Nineteen (55.9%) readmissions were defined as CDI-attributable. For patients with
      CDI-attributable readmission, the average length of stay was 6 +/- 6 days.
      CONCLUSION: Recurrent CDI leads to significant healthcare resource utilization.
      Methods of reducing the burden of recurrent CDI should be further studied.

PMID- 25057872
TI  - Continuous glucose monitoring effects on maternal glycemic control and pregnancy
      outcomes in patients with gestational diabetes mellitus: a prospective cohort
      study.
AB  - CONTEXT: Clinical evidence on the consequential effects of continuous glucose
      monitoring (CGM) on pregnancy outcomes in women with gestational diabetes
      mellitus (GDM) is scarcely available. OBJECTIVE: Our objective was to evaluate
      the effectiveness of CGM on maternal glycemic control and pregnancy outcomes in
      patients with GDM . PATIENTS: In total, 340 Chinese pregnant women with GDM were
      allocated to either the routine care group (n = 190) or the CGM group (n =150).
      DESIGN AND SETTING: This was a prospective cohort study in the Department of
      Obstetrics of GuangDong Women and Children Hospital in China. Recruitment started
      in April 2011 and stopped in August 2012. INTERVENTIONS: A 72-hour CGM system was
      used as a supplementary tool for glucose monitoring in the CGM group. PRIMARY
      OUTCOME MEASUREMENTS: The parameters of glycemic variability included mean blood
      glucose, the SD of blood glucose, mean amplitude of glycemic excursions (MAGEs),
      and the mean of daily differences. The maternal outcomes (preeclampsia and
      cesarean delivery) and composite neonatal outcomes were analyzed. RESULTS: The SD
      of blood glucose, MAGEs, and mean of daily differences values were significantly
      lower in the CGM group compared with those of the routine care group (P < .001).
      Subjects in the CGM group were at lower risk of preeclampsia and primary cesarean
      delivery compared with the routine care group (P < .05). The mean infant birth
      weight of women in the CGM group was lower than infants of women in the routine
      care group (P < .001). The MAGE was associated with birth weight (beta = 0.196, P
      < .001), and it was an independent factor for preeclampsia (odds ratio, 3.66; 95%
      confidence interval 2.16-6.20) and composite neonatal outcome (odds ratio, 1.34;
      95% confidence interval 1.01-1.77). CONCLUSIONS: The use of supplementary CGM
      combined with routine antenatal care can improve the glycemic control and
      pregnancy outcomes of patients with GDM.

PMID- 25057873
TI  - Adipose tissue MU-crystallin is a thyroid hormone-binding protein associated with
      systemic insulin sensitivity.
AB  - BACKGROUND: Circulating thyroid hormones have been described to be intrinsically
      associated with insulin sensitivity in healthy subjects. MU-Crystallin is a
      nicotinamide adenine dinucleotide phosphate-dependent thyroid hormone-binding
      protein that has been shown to bind T3 in the cytoplasm. We aimed to study MU
      Crystallin expression in adipose tissue and in muscle in association with insulin
      action and thyroid function. METHODS: MU-Crystallin gene expression was studied
      in 81 visceral and 75 sc adipose tissue samples and in 26 muscle samples from a
      cohort of subjects with a wide spectrum of adiposity (cohort 1). MU-Crystallin
      was also evaluated in 30 morbidly obese subjects in whom insulin action was
      evaluated using euglycemic clamp (cohort 2) and in 22 sc adipose tissue samples
      obtained before and after bariatric surgery-induced weight loss (cohort 3). MU
      Crystallin was also evaluated during differentiation of human adipocytes. MU
      Crystallin was overexpressed in human sc adipocytes using lentiviruses. RESULTS:
      MU-Crystallin gene expression was 2.6- to 3-fold higher in sc vs visceral adipose
      tissue in direct association with the expression of thyroid hormone receptor
      alpha 1 in cohort 1 and cohort 2. Visceral, but not sc, adipose tissue MU
      Crystallin was positively associated with the serum T3/T4 ratio in cohort 1 and
      with insulin sensitivity in cohort 2. In fact, MU-Crystallin gene expression was
      significantly decreased in visceral adipose tissue (-43%) and in muscle (-26%) in
      subjects with impaired fasting glucose and type 2 diabetes. Weight loss did not
      result in significant sc adipose tissue MU-Crystallin changes. MU-Crystallin
      overexpression led to increased insulin-induced (Ser473)Akt phosphorylation in sc
      adipocytes. During differentiation of adipocytes, MU-Crystallin gene expression
      decreased in both visceral (P = .006) and sc (P = .003) adipocytes from obese
      subjects. CONCLUSION: Visceral, but not sc, adipose tissue MU-Crystallin is an
      adipose tissue factor linked to parameters of thyroid hormone action (T3/T4
      ratio) and might mediate the interaction of thyroid function and insulin
      sensitivity.

PMID- 25057874
TI  - No association between BMD and prevalent vertebral fractures in liver transplant
      recipients at time of screening before transplantation.
AB  - CONTEXT: Osteoporosis and fractures are prevalent after orthotopic liver
      transplantation (OLT), but data on these skeletal complications are scarce in
      patients with end-stage liver disease awaiting liver transplantation. OBJECTIVE:
      To evaluate the prevalence of vertebral fractures (VFs) in OLT recipients at the
      time of screening for transplantation and to establish the association between
      bone mineral density (BMD) and these fractures before transplantation. DESIGN AND
      SETTING: We conducted a retrospective study of consecutive OLT recipients at the
      Leiden University Medical Centre between 2000 and 2011 at the time of screening
      for transplantation. Clinical, laboratory, and BMD data were extracted from
      electronic hospital records. Conventional spinal radiographs were assessed for VF
      by two independent observers using Genant's semiquantitative method. PATIENTS: In
      total, 162 of the 223 OLT recipients (median age, 51 y; 75% men) who had
      available BMD and spinal radiographs but who were not receiving bone-modifying
      treatment at screening for OLT were included in the study. MAIN OUTCOME MEASURES:
      Association between BMD and VF before transplantation. RESULTS: Osteoporosis and
      osteopenia were prevalent at the lumbar spine in 19 and 38% of subjects,
      respectively, and in 10 and 42 % at the femoral neck. VFs, mostly grade 1, were
      prevalent in 56% of the subjects. There was no association between BMD and
      prevalent VF before transplantation. CONCLUSIONS: VFs were prevalent in liver
      transplant recipients at the time of screening for transplantation, but there was
      no association between BMD and prevalent fractures. Spinal radiographs should be
      routinely performed as part of screening protocols before liver transplantation
      to enable identification of VF and allow timely intervention to potentially
      decrease or prevent skeletal morbidity after transplantation.

PMID- 25057875
TI  - Both low and high serum IGF-1 levels associate with increased risk of
      cardiovascular events in elderly men.
AB  - CONTEXT: Most previous prospective studies suggest that low serum IGF-1
      associates with increased risk of cardiovascular disease (CVD) events whereas
      other studies suggest that high serum IGF-1 associates with increased risk of CVD
      events. OBJECTIVE: We tested the hypothesis that not only low, but also high
      serum IGF-1 levels associate with increased risk of CVD events in elderly men.
      SETTING AND DESIGN: Serum IGF-1 levels were measured in 2901 elderly men (age 69
      81 years) included in the Swedish cohort of the prospective, population-based
      Osteoporotic Fractures in Men Study (MrOS), Sweden cohort. Data for CVD events
      were obtained from national Swedish registers with no loss of followup. RESULTS:
      During followup (median, 5.1 y) 589 participants experienced a CVD event. The
      association between serum IGF-1 and risk of CVD events was nonlinear, and
      restricted cubic spline Cox regression analysis revealed a U-shaped association
      between serum IGF-1 levels and CVD events (P < .01 for nonlinearity). Low as well
      as high serum IGF-1 (quintile 1 or 5 vs quintiles 2-4) significantly associated
      with increased risk for CVD events (hazard ratio [HR] = 1.25, 95% confidence
      interval, [CI], 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These
      associations remained after adjustment for prevalent CVD and multiple risk
      factors. High serum IGF-1 associated with increased risk of coronary heart
      disease (CHD) events but not with risk of cerebrovascular events. CONCLUSIONS:
      Both low and high serum IGF-1 levels are risk markers for CVD events in elderly
      men. The association between high serum IGF-1 and CVD events is mainly driven by
      CHD events.

PMID- 25057876
TI  - Insulin resistance and increased muscle cytokine levels in patients with
      mitochondrial myopathy.
AB  - CONTEXT: Mitochondrial dysfunction has been proposed to cause insulin resistance
      and that might stimulate cytokine production. OBJECTIVE: The objective of the
      study was to elucidate the association between mitochondrial myopathy, insulin
      sensitivity, and cytokine levels in muscle. DESIGN AND SETTING: This was an
      experimental, controlled study in outpatients. PARTICIPANTS: Eight overnight
      fasted patients (P) with various inherited mitochondrial myopathies and eight
      healthy subjects (C) matched for sex, age, weight, height, and physical activity
      participated in the study. INTERVENTIONS: The intervention included a 120-minute
      hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus
      lateralis muscles for 4 hours, including one-legged, knee extension exercise for
      30 minutes, was performed. MAIN OUTCOME MEASURES: Glucose infusion rate during 90
      120 minutes of insulin infusion was measured. Cytokine concentrations in
      dialysate were also measured. RESULTS: Muscle strength, percentage fat mass, and
      creatine kinase in plasma did not differ between groups. The maximal oxygen
      uptake was 21 +/- 3 (SE) (P) and 36 +/- 3(C) mL/kg.min (2P < .05). Basal insulin,
      C-peptide, and glucagon were higher in P (55 +/- 10, 980 +/- 92, and 102 +/- 13
      pM) than in C (36 +/- 12, 712 +/- 98, and 44 +/- 10 pM) (two-sided significance
      testing [2P ]< .05). The homeostasis model assessment insulin sensitivity index
      and glucose infusion rate (6.8 +/- 1.0 vs 9.4 +/- 1.3 mg/min.kg) were lower, and
      free fatty acids and glycerol at 120 minutes were higher in P vs C (2P < .05).
      Dialysate concentrations of TNF-alpha, IL-6, IL-8, IL-10, and monocyte
      chemoattractant protein-1 were higher in P vs C (2P < .05). Dialysate
      concentrations of these cytokines and of IL-1 receptor antagonist increased
      during exercise (2P < .05), identically in P and C. No differences existed in
      plasma cytokine concentrations. CONCLUSIONS: In patients with a variety of
      mitochondrial myopathies, insulin sensitivity of muscle, adipose tissue, and
      pancreatic A cells is reduced, supporting that mitochondrial function influences
      insulin action. Furthermore, a local, low-grade inflammation of potential
      clinical importance exists in the muscle of these patients.

PMID- 25057877
TI  - SPECT/CT and I131 therapy of brain metastases from follicular variant papillary
      thyroid carcinoma (FVPTC).

PMID- 25057878
TI  - Maternal perchlorate levels in women with borderline thyroid function during
      pregnancy and the cognitive development of their offspring: data from the
      Controlled Antenatal Thyroid Study.
AB  - OBJECTIVE: Thyroid dysfunction is associated with impaired cognitive development.
      Perchlorate decreases thyroidal iodine uptake, potentially reducing thyroid
      hormone production. It is unclear whether perchlorate exposure in early life
      affects neurodevelopment. DESIGN: Historical cohort analysis. PATIENTS: From 2002
      to 2006, 21,846 women at gestational age <16 weeks recruited from antenatal
      clinics in Cardiff, UK and Turin, Italy were enrolled in the Controlled Antenatal
      Thyroid Screening Study (CATS). We undertook a retrospective analysis of 487
      mother-child pairs in mothers who were hypothyroid/hypothyroxinemic during
      pregnancy and analyzed whether first trimester maternal perchlorate levels in the
      highest 10% of the study population were associated with increased odds of
      offspring IQ being in the lowest 10% at 3 years of age. MAIN OUTCOME MEASURES:
      Maternal urinary perchlorate, offspring IQ. RESULTS: Urine perchlorate was
      detectable in all women (median 2.58 MUg/L); iodine levels were low (median 72
      MUg/L). Maternal perchlorate levels in the highest 10% of the population
      increased the odds of offspring IQ being in the lowest 10% OR = 3.14 (95% CI
      1.38, 7.13) P = .006 with a greater negative impact observed on verbal OR = 3.14
      (95% CI 1.42, 6.90) P = .005 than performance IQ. Maternal levothyroxine therapy
      did not reduce the negative impact of perchlorate on offspring IQ. CONCLUSIONS:
      This is the first study using individual-level patient data to study maternal
      perchlorate exposure and offspring neurodevelopment and suggests that high-end
      maternal perchlorate levels in hypothyroid/hypothyroxinemic pregnant women have
      an adverse effect on offspring cognitive development, not affected by maternal
      levothyroxine therapy. These results require replication in additional studies,
      including in the euthyroid population.

PMID- 25057879
TI  - Circulating miRNA95 and miRNA190 are sensitive markers for the differential
      diagnosis of thyroid nodules in a Caucasian population.
AB  - CONTEXT: MicroRNA (miRNAs) are nonprotein-encoding RNAs that regulate gene
      expression and enable the distinction of benign from malignant tissues in human
      cancers. OBJECTIVE: We investigated the role of miRNA circulating in the blood
      for the differential diagnosis of thyroid nodules. SETTING AND DESIGN: miRNA
      profiling was assessed by TaqMan Array Human MicroRNA A Cards v2.0 in pooled sera
      from 12 healthy subjects (HS), 12 nodular goiters (NG), and 12 patients with
      papillary thyroid cancer (PTC) (cohort 1). From this analysis, we selected eight
      miRNAs that were validated in individual samples (same of cohort 1) by qRT-PCR.
      Four miRNAs were confirmed differentially expressed in PTC and were analyzed in a
      larger second cohort. RESULTS: The profiling analysis revealed eight miRNAs
      (miRNA579, -95, -29b, 5-01-3p, -548d-5p down-regulated, and miR190, -362-3p, 
      518a-5p up-regulated) which differ in PTC compared with NG and HS. After the
      validation in individual samples, we confirmed as differentially expressed
      miRNA579, -95, -29b, and miRNA190. These miRNAs were further validated in a
      second cohort of sera from 79 PTC, 80 NG, and 41 HS. MiRNA95 had a sensitivity of
      94.9%, which reached 100% in a multivariate risk model combined with miRNA190. We
      developed a mathematical formula that calculates the probability of malignancy
      with a cut-off value of 0.5 above which the patient was at high risk of
      malignancy. CONCLUSIONS: We have identified for the first time two miRNAs
      differently expressed in serum of PTC patients who in combination allow the
      differential diagnosis of thyroid nodules with great accuracy in our study
      population. Additional studies are required; however, to define whether these
      results will also be generalized across other patient populations."

PMID- 25057880
TI  - A novel KCNJ5-insT149 somatic mutation close to, but outside, the selectivity
      filter causes resistant hypertension by loss of selectivity for potassium.
AB  - CONTEXT: Understanding the function of the KCNJ5 potassium channel through
      characterization of naturally occurring novel mutations is key for dissecting the
      mechanism(s) of autonomous aldosterone secretion in primary aldosteronism.
      OBJECTIVE: We sought for such novel KCNJ5 channel mutations in a large database
      of patients with aldosterone-producing adenomas (APAs). METHODS: We discovered a
      novel somatic c.446insAAC insertion, resulting in the mutant protein KCNJ5
      insT149, in a patient with severe drug-resistant hypertension among 195
      consecutive patients with a conclusive diagnosis of APA, 24.6% of whom showed
      somatic KCNJ5 mutations. By site-directed mutagenesis, we created the mutated
      cDNA that was transfected, along with KCNJ3 cDNA, in mammalian cells. We also
      localized CYP11B2 in the excised adrenal gland with immunohistochemistry and
      immunofluorescence using an antibody specific to human CYP11B2. Whole-cell patch
      clamp recordings, CYP11B2 mRNA, aldosterone measurement, and molecular modeling
      were performed to characterize the novel KCNJ5-insT149 mutation. RESULTS:
      Compared with wild-type and mock-transfected adrenocortical cells, HAC15 cells
      expressing the mutant KCNJ5 showed increased CYP11B2 expression and aldosterone
      secretion. Mammalian cells expressing the mutated KCNJ5-insT149 channel exhibited
      a strong Na(+) inward current and, in parallel, a substantial rise in
      intracellular Ca(2+), caused by activation of voltage-gated Ca(2+) channels and
      reduced Ca(2+) elimination by Na(+)/Ca(2+) exchangers, as well as an increased
      production of aldosterone. CONCLUSIONS: This novel mutation shows pathological
      Na(+) permeability, membrane depolarization, raised cytosolic Ca(2+), and
      increased aldosterone synthesis. Hence, a novel KCNJ5 channelopathy located after
      the pore alpha-helix preceding the selectivity filter causes constitutive
      secretion of aldosterone with ensuing resistant hypertension in a patient with a
      small APA.

PMID- 25057881
TI  - A novel variant in CDKN1C is associated with intrauterine growth restriction,
      short stature, and early-adulthood-onset diabetes.
AB  - CONTEXT: CDKN1C, a cyclin-dependent kinase inhibitor and negative regulator of
      cellular proliferation, is paternally imprinted and has been shown to regulate
      beta-cell proliferation. CDKN1C mutations are associated with growth disorders,
      including Beckwith-Wiedemann syndrome and IMAGe syndrome. OBJECTIVE: To
      investigate the genetic basis for a familial disorder characterized by
      intrauterine growth restriction, short stature, and early-adulthood-onset
      diabetes. DESIGN, SETTING, AND PARTICIPANTS: Genomic DNA samples (15 affected and
      26 unaffected from a six-generation pedigree) were analyzed by genome-wide single
      nucleotide polymorphism arrays, whole exome and Sanger sequencing, and multiplex
      ligation-dependent probe amplification. MAIN OUTCOME MEASURE(S): Subjects were
      assessed for height, weight, adrenal gland size, ACTH, diabetes status, and
      testis volume. Linkage and sequence analyses were performed, and the identified
      genetic variant was functionally evaluated in reconstitution studies. RESULTS:
      The pedigree followed a paternally imprinted pattern of inheritance, and genetic
      linkage analysis identified a single significant 2.6-megabase locus on chromosome
      11p15, within the imprinting center region 2. Multiplex ligation-dependent probe
      amplification did not detect copy number variants or methylation abnormalities.
      Whole exome sequencing revealed a single novel variant in the proliferating cell
      nuclear antigen-binding region of CDKN1C (c.842G>T, p.R281I) that co-segregated
      with affected status and, unlike variants found in IMAGe, did not entirely
      abrogate proliferating cell nuclear antigen binding. Clinical assessments
      revealed that affected individuals had low testicular volume but normal adrenal
      function. CONCLUSIONS: We report a novel CDKN1C mutation associated with features
      of IMAGe syndrome, but without adrenal insufficiency or metaphyseal dysplasia,
      and characterized by early-adulthood-onset diabetes. Our data expand the range of
      phenotypes observed with CDKN1C defects and suggest that CDKN1C mutations may
      represent a novel monogenic form of diabetes.

PMID- 25057882
TI  - TSH levels and risk of miscarriage in women on long-term levothyroxine: a
      community-based study.
AB  - CONTEXT: Thyroid dysfunction is associated with adverse obstetric outcomes, but
      there is limited information on pregnancy outcomes in women established on
      levothyroxine. OBJECTIVE: The objective of the study was to determine the
      relationship between TSH levels and pregnancy outcomes in levothyroxine-treated
      women in a large community-based database. DESIGN: This was a historical cohort
      analysis. PATIENTS: Individuals with a first prescription of levothyroxine from
      2001 through 2009 (n = 55 501) were identified from the UK General Practice
      Research Database (population 5 million). Of these, we identified 7978 women of
      child-bearing age (18-45 y) and 1013 pregnancies in which levothyroxine had been
      initiated at least 6 months before conception. MAIN OUTCOME MEASURES: TSH,
      miscarriage/delivery status, and obstetric outcomes were measured. RESULTS: Forty
      six percent of levothyroxine-treated women aged 18-45 years had a TSH level
      greater than 2.5 mU/L (recommended upper level in the first trimester). Among
      pregnant women who had their TSH measured in the first trimester, 62.8% had a TSH
      level greater than 2.5 mU/L, with 7.4% greater than 10 mU/L. Women with TSH
      greater than 2.5 mU/L in the first trimester had an increased risk of miscarriage
      compared with women with TSH 0.2-2.5 mU/L after adjusting for age, year of
      pregnancy, diabetes, and social class (P = .008). The risk of miscarriage was
      increased in women with TSH 4.51-10 mU/L [odds ratio (OR) 1.80, 95% confidence
      interval (CI) 1.03, 3.14)] and TSH greater than 10 mU/L (OR 3.95, 95% CI 1.87,
      8.37) but not with TSH 2.51-4.5 mU/L (OR 1.09, 95% CI 0.61, 1.93). CONCLUSIONS:
      The majority of levothyroxine-treated women have early gestational TSH levels
      above the recommended targets (>2.5 mU/L) with a strong risk of miscarriage at
      levels exceeding 4.5 mU/L. There is an urgent need to improve the adequacy of
      thyroid hormone replacement in early pregnancy.

PMID- 25057883
TI  - Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease
      patients.
AB  - BACKGROUND: The chronic kidney disease (CKD)-mineral and bone disorder (MBD)
      syndrome is an important contributor to the CKD-associated cardiovascular disease
      and high mortality rates. Sclerostin, a protein synthesized in osteocytes, is a
      potent downregulator of bone metabolism and a novel candidate for the bone
      vascular axis in CKD patients. We tested whether serum sclerostin values are
      predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD
      population. METHODS: Serum sclerostin was obtained from 173 CKD (stage 3-5) and
      47 control patients, and its concentration was correlated with estimated
      glomerular filtration rate and to mineral and vascular abnormalities that are
      present in the CKD evolution. All-cause mortality and CVEs were also analyzed in
      relation to serum sclerostin values. RESULTS: Patients with CKD showed higher
      sclerostin levels (median 63.5 pmol/L vs 52 pmol/L, P < .001) than controls, with
      values progressively higher across the CKD stages. In univariate analysis, serum
      sclerostin concentrations were correlated with gender, estimated glomerular
      filtration rate, flow-mediated dilatation, and endothelium-independent
      vasodilatation as markers of endothelial dysfunction and with different serum CKD
      MBD-associated parameters. However, in multivariate analysis, only gender,
      fibroblast growth factor-23, phosphate, flow-mediated dilatation, and cholesterol
      remained significantly associated with sclerostin levels. During the
      observational period, there were 19 deaths and 50 CVEs. In survival analysis,
      different sclerostin levels were associated with all-cause mortality and CVEs in
      these patients. CONCLUSIONS: This is the first study that shows that serum
      sclerostin values are associated, even after multiple adjustments, with fatal and
      nonfatal CVEs in a nondialyzed CKD population.

PMID- 25057884
TI  - Novel somatic mutations in the catalytic subunit of the protein kinase A as a
      cause of adrenal Cushing's syndrome: a European multicentric study.
AB  - CONTEXT: Somatic mutations in PRKACA gene, encoding the catalytic subunit of
      protein kinase A (PKA), have been recently found in a high proportion of sporadic
      adenomas associated with Cushing's syndrome. The aim was to analyze the PRKACA
      mutation in a large cohort of patients with adrenocortical masses. METHODS:
      Samples from nine European centers were included (Germany, n = 4; Italy, n = 4;
      France, n = 1). Samples were drawn from 149 patients with nonsecreting adenomas
      (n = 32 + 2 peritumoral), subclinical hypercortisolism (n = 36), Cushing's
      syndrome (n = 64 + 2 peritumoral), androgen-producing tumors (n = 4),
      adrenocortical carcinomas (n = 5 + 2 peritumoral), and primary bilateral
      macronodular adrenal hyperplasias (n = 8). Blood samples were available from
      patients with nonsecreting adenomas (n = 15), subclinical hypercortisolism (n =
      10), and Cushing's syndrome (n = 35). Clinical and hormonal data were collected.
      DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct
      sequencing were performed. RESULTS: PRKACA heterozygous mutations were found in
      22/64 samples of Cushing's syndrome patients (34%). No mutations were found in
      peritumoral tissue and blood samples or in other tumors examined. The c.617A>C
      (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were
      identified: c.600_601insGTG/p.Cys200_Gly201insVal in three patients and
      c.639C>G+c.638_640insATTATCCTGAGG/p.Ser213Arg+p.Leu212_Lys214insIle-Ile-Leu-Arg)
      in one. All the mutations involved a region implicated in interaction between PKA
      regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed
      higher levels of cortisol after dexamethasone test and a smaller adenoma size,
      compared with nonmutated subjects. CONCLUSIONS: These data confirm and extend
      previous observations that somatic PRKACA mutations are specific for
      adrenocortical adenomas causing Cushing's syndrome.

PMID- 25057886
TI  - Unsuspected diagnosis of uterine leiomyosarcoma after laparoscopic myomectomy.

PMID- 25057885
TI  - 5-Hydroxymethylcytosine promotes proliferation of human uterine leiomyoma: a
      biological link to a new epigenetic modification in benign tumors.
AB  - CONTEXT: Uterine leiomyoma, or fibroids, represent the most common benign tumors
      of the female reproductive tract. A newly discovered epigenetic modification, 5
      hydroxymethylation (5-hmC), and its regulators, the TET (Ten Eleven
      Translocation) enzymes, were implicated in the pathology of malignant tumors;
      however, their roles in benign tumors, including uterine fibroids, remain
      unknown. OBJECTIVE: To determine the role of 5-hmC and TET proteins in the
      pathogenesis of leiomyoma using human uterine leiomyoma and normal matched
      myometrial tissues and primary cells. DESIGN: 5-hmC levels were determined by
      ELISA and immunofluorescent staining in matched myometrial and leiomyoma tissues.
      TET expression was analyzed by quantitative RT-PCR and immunoblotting. TET1 or
      TET3 were silenced or inhibited by small interfering RNA or 2-hydroxyglutarate to
      study their effects on 5-hmC content and cell proliferation. RESULTS: We
      demonstrated significantly higher 5-hmC levels in the genomic DNA of leiomyoma
      tissue compared to normal myometrial tissue. The increase in 5-hmC levels was
      associated with the up-regulation of TET1 or TET3 mRNA and protein expression in
      leiomyoma tissue. TET1 or TET3 knockdown significantly reduced 5-hmC levels in
      leiomyoma cells and decreased cell proliferation. Treatment with 2
      hydroxyglutarate, a competitive TET enzyme inhibitor, significantly decreased
      both 5-hmC content and cell proliferation of leiomyoma cells. CONCLUSION: An
      epigenetic imbalance in the 5-hmC content of leiomyoma tissue, caused by up
      regulation of the TET1 and TET3 enzymes, might lead to discovery of new
      therapeutic targets in leiomyoma.

PMID- 25057887
TI  - Research involving anxiety in non-human primates has potential implications for
      the assessment and treatment of anxiety in autism spectrum disorder: A
      translational literature review.
AB  - OBJECTIVE: The purpose of this translational review (i.e. moving from basic
      primate research toward possible human applications) was to summarize non-human
      primate literature on anxiety to inform the development of future assessments of
      anxiety in non-verbal individuals with autism spectrum disorder (ASD). METHODS:
      Systematic searches of databases identified 67 studies that met inclusion
      criteria. Each study was analysed and summarised in terms of (a) strategies used
      to evoke anxiety, (b) non-verbal behavioural indicators of anxiety and (c)
      physiological indicators of anxiety. RESULTS: Eighteen strategies were used to
      evoke anxiety, 48 non-verbal behavioural indicators and 17 physiological
      indicators of anxiety were measured. CONCLUSIONS: A number of the strategies used
      with non-human primates, if modified carefully, could be considered in the
      ongoing effort to study anxiety in individuals with ASD. Potential applications
      to the assessment of anxiety in humans with ASD are discussed.

PMID- 25057889
TI  - TALEN-mediated genome editing: prospects and perspectives.
AB  - Genome editing is the practice of making predetermined and precise changes to a
      genome by controlling the location of DNA DSBs (double-strand breaks) and
      manipulating the cell's repair mechanisms. This technology results from
      harnessing natural processes that have taken decades and multiple lines of
      inquiry to understand. Through many false starts and iterative technology
      advances, the goal of genome editing is just now falling under the control of
      human hands as a routine and broadly applicable method. The present review
      attempts to define the technique and capture the discovery process while
      following its evolution from meganucleases and zinc finger nucleases to the
      current state of the art: TALEN (transcription-activator-like effector nuclease)
      technology. We also discuss factors that influence success, technical challenges
      and future prospects of this quickly evolving area of study and application. 

PMID- 25057890
TI  - Chaperone turns gatekeeper: PCBP2 and DMT1 form an iron-transport pipeline.
AB  - How is cellular iron (Fe) uptake and efflux regulated in mammalian cells? In this
      issue of the Biochemical Journal, Yanatori et al. report for the first time that
      a member of the emerging PCBP [poly(rC)-binding protein] Fe-chaperone family,
      PCBP2, physically interacts with the major Fe importer DMT1 (divalent metal
      transporter 1) and the Fe exporter FPN1 (ferroportin 1). In both cases, the
      interaction of the Fe transporter with PCBP2 is Fe-dependent. Interestingly,
      another PCBP Fe-chaperone, PCBP1, does not appear to bind to DMT1. Strikingly,
      the PCBP2-DMT1 interaction is required for DMT1-dependent cellular Fe uptake,
      suggesting that, in addition to functioning as an intracellular Fe chaperone,
      PCBP2 may be a molecular 'gate- keeper' for transmembrane Fe transport. These new
      data hint at the possibility that PCBP2 may be a component of a yet-to-be
      described Fe-transport metabolon that engages in Fe channelling to and from Fe
      transporters and intracellular sites. 

PMID- 25057891
TI  - Comparison of second-echelon treatments for Meniere's disease.
AB  - IMPORTANCE: To compare the efficacy of treatments commonly offered to patients
      with Meniere's disease who fail conservative medical therapy including diuretics
      and a sodium-restricted diet. OBJECTIVES: This study compared three second
      echelon treatments: the Meniett device, endolymphatic sac decompression, and
      intratympanic gentamicin injections to determine their comparative effectiveness
      and capacity to mitigate against the necessity of a surgical labyrinthectomy.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational study at an
      academic tertiary care center. Patients with Meniere's disease who failed primary
      medical management were evaluated after treatment with a Meniett device (n=20),
      endolymphatic sac decompression (n=23) or intratympanic gentamicin injections
      (n=17). Cases were included if auditory and vertigo control data were available
      before and a minimum of two years after treatment, in patients without previous
      otologic surgery or intratympanic injections. Average age ranged from 54 to 75
      years. INTERVENTIONS: Use of the Meniett device, endolymphatic sac shunt
      decompression surgery or intratympanic gentamicin injections using variable doses
      and injection schedules. MAIN OUTCOMES AND MEASURES: Proportion of patients with
      vertigo control and hearing preservation by a modified version of the AAO-HNS
      criteria after second-echelon treatment, thus not requiring definitive
      labyrinthectomy. RESULTS: Despite endolymphatic sac surgery demonstrating a
      longer duration (61 months) prior to labyrinthectomy, no differences were found
      between the 3 treatment options in terms of patients going on to definitive
      labyrinthectomy or in the number of months of symptom relief following treatment.
      There was also no difference in residual auditory perception across the 3 groups.
      CONCLUSIONS AND RELEVANCE: No significant therapeutic differences were found
      between the studied second-echelon treatments for symptom relief of Meniere's
      disease.

PMID- 25057888
TI  - The molecular regulation of Janus kinase (JAK) activation.
AB  - The JAK (Janus kinase) family members serve essential roles as the intracellular
      signalling effectors of cytokine receptors. This family, comprising JAK1, JAK2,
      JAK3 and TYK2 (tyrosine kinase 2), was first described more than 20 years ago,
      but the complexities underlying their activation, regulation and pleiotropic
      signalling functions are still being explored. Here, we review the current
      knowledge of their physiological functions and the causative role of activating
      and inactivating JAK mutations in human diseases, including haemopoietic
      malignancies, immunodeficiency and inflammatory diseases. At the molecular level,
      recent studies have greatly advanced our knowledge of the structures and
      organization of the component FERM (4.1/ezrin/radixin/moesin)-SH2 (Src homology
      2), pseudokinase and kinase domains within the JAKs, the mechanism of JAK
      activation and, in particular, the role of the pseudokinase domain as a
      suppressor of the adjacent tyrosine kinase domain's catalytic activity. We also
      review recent advances in our understanding of the mechanisms of negative
      regulation exerted by the SH2 domain-containing proteins, SOCS (suppressors of
      cytokine signalling) proteins and LNK. These recent studies highlight the
      diversity of regulatory mechanisms utilized by the JAK family to maintain
      signalling fidelity, and suggest alternative therapeutic strategies to complement
      existing ATP-competitive kinase inhibitors.

PMID- 25057892
TI  - Free-classification of perceptually similar speakers with dysarthria.
AB  - PURPOSE: In this investigation, the construct of perceptual similarity was
      explored in the dysarthrias. Specifically, we employed an auditory free
      classification task to determine whether listeners could cluster speakers by
      perceptual similarity, whether the clusters mapped to acoustic metrics, and
      whether the clusters were constrained by dysarthria subtype diagnosis. METHOD:
      Twenty-three listeners blinded to speakers' medical and dysarthria subtype
      diagnoses participated. The task was to group together (drag and drop) the icons
      corresponding to 33 speakers with dysarthria on the basis of how similar they
      sounded. Cluster analysis and multidimensional scaling (MDS) modeled the
      perceptual dimensions underlying similarity. Acoustic metrics and perceptual
      judgments were used in correlation analyses to facilitate interpretation of the
      derived dimensions. RESULTS: Six clusters of similar-sounding speakers and 3
      perceptual dimensions underlying similarity were revealed. The clusters of
      similar-sounding speakers were not constrained by dysarthria subtype diagnosis.
      The 3 perceptual dimensions revealed by MDS were correlated with metrics for
      articulation rate, intelligibility, and vocal quality, respectively. CONCLUSIONS:
      This study shows (a) feasibility of a free-classification approach for studying
      perceptual similarity in dysarthria, (b) correspondence between acoustic and
      perceptual metrics to clusters of similar-sounding speakers, and (c) similarity
      judgments transcended dysarthria subtype diagnosis.

PMID- 25057893
TI  - Using informatics and the electronic medical record to describe antimicrobial use
      in the clinical management of diarrhea cases at 12 companion animal practices.
AB  - Antimicrobial drugs may be used to treat diarrheal illness in companion animals.
      It is important to monitor antimicrobial use to better understand trends and
      patterns in antimicrobial resistance. There is no monitoring of antimicrobial use
      in companion animals in Canada. To explore how the use of electronic medical
      records could contribute to the ongoing, systematic collection of antimicrobial
      use data in companion animals, anonymized electronic medical records were
      extracted from 12 participating companion animal practices and warehoused at the
      University of Calgary. We used the pre-diagnostic, clinical features of diarrhea
      as the case definition in this study. Using text-mining technologies, cases of
      diarrhea were described by each of the following variables: diagnostic laboratory
      tests performed, the etiological diagnosis and antimicrobial therapies. The
      ability of the text miner to accurately describe the cases for each of the
      variables was evaluated. It could not reliably classify cases in terms of
      diagnostic tests or etiological diagnosis; a manual review of a random sample of
      500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent
      diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text
      mining, compared to a human reviewer, could accurately identify cases that had
      been treated with antimicrobials with high sensitivity (92%, 95% confidence
      interval, 88.1%-95.4%) and specificity (85%, 95% confidence interval, 80.2%
      89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were
      treated with antimicrobials. Some temporal trends and patterns of the
      antimicrobial use are described. The results from this study suggest that
      informatics and the electronic medical records could be useful for monitoring
      trends in antimicrobial use. 

PMID- 25057895
TI  - Causation of cigarette smoke-induced emphysema by p-benzoquinone and its
      prevention by vitamin C.
AB  - Cigarette smoke (CS) is the strongest risk factor for emphysema. However, the
      mechanism of the disease is not clear. One reason is that each puff of CS is a
      complex mixture of approximately 4,000 chemicals, and it is yet to be known which
      of these chemical(s) are directly involved in the pathogenesis of lung injury in
      emphysema. The purpose of this study was to demonstrate that p-benzoquinone (p
      BQ) produced in the lungs of CS-exposed guinea pigs is a causative factor for
      destruction of alveolar cells resulting in emphysema that is prevented by vitamin
      C. Vitamin C-restricted guinea pigs were subjected to whole-body CS exposure from
      five Kentucky research cigarettes (3R4F) per day or intramuscular injection of p
      BQ in amounts approximately produced in the lung from CS exposure with and
      without oral supplementation of vitamin C. Progressive exposure of CS or p-BQ
      treatment caused progressive accumulation of p-BQ in the lung that was
      accompanied by destruction of alveolar cells and emphysema. The pathogenesis
      involved was arylation, oxidative stress, inflammation, and apoptosis. Vitamin C
      (30 mg/kg body weight/d), a potential antagonist of p-BQ, prevented accumulation
      of p-BQ in the lung and the pathogenesis of emphysema. Our study provides the
      first proof that inactivation of p-BQ, a causative factor of emphysema in CS
      exposed lung, could constitute a novel and effective approach in the prevention
      of emphysema. We consider that a moderately high dose of vitamin C may be a
      simple preventive therapy for emphysema in chronic smokers. 

PMID- 25057896
TI  - Polymeric micelle nanocarriers for the cutaneous delivery of tacrolimus: a
      targeted approach for the treatment of psoriasis.
AB  - Tacrolimus (TAC) suffers from poor cutaneous bioavailability when administered
      topically using conventional vehicles with the consequence that although it is
      indicated for the treatment of atopic dermatitis, it has poor efficacy against
      psoriasis. The aim of this work was to formulate TAC loaded polymeric micelles
      using the biodegradable and biocompatible methoxy-poly(ethylene glycol)-dihexyl
      substituted polylactide (MPEG-dihexPLA) diblock copolymer and to investigate
      their potential for targeted delivery of TAC into the epidermis and upper dermis.
      Micelle formulations were characterized with respect to drug content, stability,
      and size. An optimal 0.1% micelle formulation was developed and shown to be
      stable over a period of 7 months at 4  degrees C; micelle diameters ranged from
      10 to 50 nm. Delivery experiments using human skin and involving quantification
      by UHPLC-MS/MS demonstrated that this formulation resulted in significantly
      greater TAC deposition in skin than that with Protopic (0.1% w/w; TAC ointment),
      (1.50 +/- 0.59 and 0.47 +/- 0.20 MUg/cm(2), respectively). The cutaneous
      biodistribution profile of TAC in the upper 400 MUm of tissue (at a resolution of
      20 MUm) demonstrated that the increase in cutaneous drug levels was due to
      improved TAC deposition in the stratum corneum, viable epidermis, and upper
      dermis. Given that there was no increase in the amount of TAC in deeper skin
      layers or any transdermal permeation, the results suggested that it would be
      possible to increase TAC levels selectively in the target tissue without
      increasing systemic absorption and the risk of side effects in vivo. Micelle
      distribution and molecular penetration pathways were subsequently visualized with
      confocal laser scanning microscopy (CLSM) using a fluorescently labeled copolymer
      and fluorescent dyes. The CLSM study indicated that the copolymer was unable to
      cross the stratum corneum and that release of the micelle "payload" was dependent
      on the molecular properties of the "cargo" as evidenced by the different
      behaviors of DiO and fluorescein. A preferential deposition of micelles into the
      hair follicle was also confirmed by CLSM. Overall, the results indicate that MPEG
      dihexPLA micelles are highly efficient nanocarriers for the selective cutaneous
      delivery of tacrolimus, superior to the marketed formulation (Protopic).
      Furthermore, they may also have significant potential for targeted delivery to
      the hair follicle. 

PMID- 25057897
TI  - Anionic polycyclization entry to tricycles related to quassinoids and terpenoids:
      a stereocontrolled total synthesis of (+)-cassaine.
AB  - A full account of our anionic polycyclization approach to access highly
      functionalized tricycles related to quassinoids and terpenoids from several
      optically active bicyclic enone systems and Nazarov reagents is presented. (+)
      Carvone is the only chiral source used to fix the entire stereochemistry of all
      of the tricycles, and the stereochemical outcome of this process was
      unambiguously determined by X-ray crystallographic analysis. The utility of this
      strategy was demonstrated by the stereocontrolled construction of advanced
      tricycles related to the highly potent anticancer natural product bruceantin, a
      member of quassinoid family, and the total synthesis of the cardioactive
      terpenoid (+)-cassaine, a nonsteroidal inhibitor of Na(+)-K(+)-ATPase. 

PMID- 25057898
TI  - High throughput profiling of antibiotic resistance genes in urban park soils with
      reclaimed water irrigation.
AB  - Reclaimed water irrigation (RWI) in urban environments is becoming popular, due
      to rapid urbanization and water shortage. The continuous release of residual
      antibiotics and antibiotic resistance genes (ARGs) from reclaimed water could
      result in the dissemination of ARGs in the downstream environment. This study
      provides a comprehensive profile of ARGs in park soils exposed to RWI through a
      high-throughput quantitative PCR approach. 147 ARGs encoding for resistance to a
      broad-spectrum of antibiotics were detected among all park soil samples.
      Aminoglycoside and beta-lactam were the two most dominant types of ARGs, and
      antibiotic deactivation and efflux pump were the two most dominant mechanisms in
      these RWI samples. The total enrichment of ARGs varied from 99.3-fold to 8655.3
      fold compared to respective controls. Six to 60 ARGs were statistically enriched
      among these RWI samples. Four transposase genes were detected in RWI samples.
      TnpA-04 was the most enriched transposase gene with an enrichment was up to
      2501.3-fold in Urumqi RWI samples compared with control soil samples.
      Furthermore, significantly positive correlation was found between ARGs and
      transposase abundances, indicating that transposase might be involved in the
      propagation of ARGs. This study demonstrated that RWI resulted in the enrichment
      of ARGs in urban park soils. 

PMID- 25057899
TI  - Design, synthesis and pharmacological evaluation of novel vanadium-containing
      complexes as antidiabetic agents.
AB  - Based on the data about structure and antidiabetic activity of twenty seven
      vanadium and zinc coordination complexes collected from literature we developed
      QSAR models using the GUSAR program. These QSAR models were applied to 10 novel
      vanadium coordination complexes designed in silico in order to predict their
      hypoglycemic action. The five most promising substances with predicted potent
      hypoglycemic action were selected for chemical synthesis and pharmacological
      evaluation. The selected coordination vanadium complexes were synthesized and
      tested in vitro and in vivo for their hypoglycemic activities and acute rat
      toxicity. Estimation of acute rat toxicity of these five vanadium complexes was
      performed using a freely available web-resource
      (http://way2drug.com/GUSAR/acutoxpredict.html). It has shown that the selected
      compounds belong to the class of moderate toxic pharmaceutical agents, according
      to the scale of Hodge and Sterner. Comparison with the predicted data has
      demonstrated a reasonable correspondence between the experimental and predicted
      values of hypoglycemic activity and toxicity. Bis{tert
      butyl[amino(imino)methyl]carbamato}oxovanadium (IV) and sodium(2,2'-Bipyridyl)oxo
      diperoxovanadate(V) octahydrate were identified as the most potent hypoglycemic
      agents among the synthesized compounds. 

PMID- 25057900
TI  - Silencing is noisy: population and cell level noise in telomere-adjacent genes is
      dependent on telomere position and sir2.
AB  - Cell-to-cell gene expression noise is thought to be an important mechanism for
      generating phenotypic diversity. Furthermore, telomeric regions are major sites
      for gene amplification, which is thought to drive genetic diversity. Here we
      found that individual subtelomeric TLO genes exhibit increased variation in
      transcript and protein levels at both the cell-to-cell level as well as at the
      population-level. The cell-to-cell variation, termed Telomere-Adjacent Gene
      Expression Noise (TAGEN) was largely intrinsic noise and was dependent upon
      genome position: noise was reduced when a TLO gene was expressed at an ectopic
      internal locus and noise was elevated when a non-telomeric gene was expressed at
      a telomere-adjacent locus. This position-dependent TAGEN also was dependent on
      Sir2p, an NAD+-dependent histone deacetylase. Finally, we found that telomere
      silencing and TAGEN are tightly linked and regulated in cis: selection for either
      silencing or activation of a TLO-adjacent URA3 gene resulted in reduced noise at
      the neighboring TLO but not at other TLO genes. This provides experimental
      support to computational predictions that the ability to shift between silent and
      active chromatin states has a major effect on cell-to-cell noise. Furthermore, it
      demonstrates that these shifts affect the degree of expression variation at each
      telomere individually. 

PMID- 25057901
TI  - Identification of human complement factor B as a novel biomarker candidate for
      pancreatic ductal adenocarcinoma.
AB  - Pancreatic cancer (PC; pancreatic ductal adenocarcinoma) is characterized by
      significant morbidity and mortality worldwide. Although carbohydrate antigen (CA)
      19-9 has been known as a PC biomarker, it is not commonly used for general
      screening because of its low sensitivity and specificity. Therefore, there is an
      urgent need to develop a new biomarker for PC diagnosis in the earlier stage of
      cancer. To search for a novel serologic PC biomarker, we carried out an
      integrated proteomic analysis for a total of 185 pooled or individual plasma from
      healthy donors and patients with five disease groups including chronic
      pancreatitis (CP), PC, and other cancers (e.g., hepatocellular carcinoma,
      cholangiocarcinoma, and gastric cancer) and identified complement factor b (CFB)
      as a candidate serologic biomarker for PC diagnosis. Immunoblot analysis of CFB
      revealed more than two times higher expression in plasma samples from PC patients
      compared with plasma from individuals without PC. Immunoprecipitation coupled to
      mass spectrometry analysis confirmed both molecular identity and higher
      expression of CFB in PC samples. CFB showed distinctly higher specificity than CA
      19-9 for PC against other types of digestive cancers and in discriminating PC
      patients from non-PC patients (p < 0.0001). In receiver operator characteristic
      curve analysis, CFB showed an area under curve of 0.958 (95% CI: 0.956 to 0.959)
      compared with 0.833 (95% CI: 0.829 to 0.837) for CA 19-9. Furthermore, the Y
      index of CFB was much higher than that of CA 19-9 (71.0 vs 50.4), suggesting that
      CFB outperforms CA 19-9 in discriminating PC from CP and other gastrointestinal
      cancers. This was further supported by immunoprecipitation and qRT-PCR assays
      showing higher expression of CFB in PC cell lines than in normal cell lines. A
      combination of CFB and CA 19-9 showed markedly improved sensitivity (90.1 vs
      73.1%) over that of CFB alone in the diagnosis of PC against non-PC, with similar
      specificity (97.2 vs 97.9%). Thus, our results identify CFB as a novel serologic
      PC biomarker candidate and warrant further investigation into a large-scale
      validation and its role in molecular mechanism of pancreatic carcinogenesis. 

PMID- 25057903
TI  - Origin of yellow-band emission in epitaxially grown GaN nanowire arrays.
AB  - Here, we report the origin of the yellow-band emission in epitaxial GaN nanowire
      arrays grown under carbon-free conditions. GaN nanowires directly grown on [0001]
      oriented sapphire substrate exhibit an obvious and broad yellow-band in the
      visible range 400-800 nm, whereas the insertion of Al/Au layers in GaN-sapphire
      interface significantly depresses the visible emission, and only a sharp peak in
      the UV range (369 nm) can be observed. The persuasive differences in
      cathodoluminescence provide direct evidence for demonstrating that the origin of
      the yellow-band emission in GaN nanowire arrays arises from dislocation
      threading. The idea using buffering/barrier layers to isolate the dislocation
      threading in epitaxially grown GaN nanowires can be extended to the rational
      synthesis and structural defect controlling of a wide range of semiconductor
      films and nanostructures with superior crystal quality and excellent luminescence
      property. 

PMID- 25057902
TI  - The role of N-acetyltransferase 8 in mesenchymal stem cell-based therapy for
      liver ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: To evaluate the impact of mesenchymal stem cells (MSCs) against
      hepatic I/R injury and explore the role of N-acetyltransferase 8 (NAT8) in the
      process. METHODS: We investigated the potential of injected MSCs systemically via
      the tail vein in healing injuried liver of the SD rat model of 70% hepatic I/R
      injury by measuring the biochemical and pathologic alterations. Subsequently, we
      evaluated the expression levels of NAT8 by western blotting in vivo.
      Concurrently, hydrogen peroxide (H2O2)-induced apoptosis in the human normal
      liver cell line L02 was performed in vitro to evaluate the protective effects of
      MSC conditioned medium (MSC-CM) on L02 cells. In addition, we downregulated and
      upregulated NAT8 expression in L02 cells and induced apoptosis by using H2O2 to
      study the protective role of NAT8. RESULTS: MSCs implantation led to a
      significant reduced liver enzyme levels, an advanced protection in the
      histopathological findings of the acutely injured liver and a significantly lower
      percentage of TUNEL-positive cells, which were increased after I/R injury. In
      vitro assays, MSC-CM inhibited hepatocyte apoptosis induced by H2O2. Moreover,
      overexpression or downregulation of NAT8 prevented or aggravated hepatocyte
      apoptosis induced by H2O2, respectively. CONCLUSIONS: MSC transplantation
      provides support to the I/R-injured liver by inhibiting hepatocellular apoptosis
      and stimulating NAT8 regeneration.

PMID- 25057904
TI  - beta-Agarofurans and Sesquiterpene Pyridine Alkaloids from Maytenus spinosa.
AB  - Nine new beta-dihydroagarofurans (1-9) and four new sesquiterpene pyridine
      alkaloids (10-13) were isolated from the leaves of Maytenus spinosa. Their
      structures were determined mainly by 1D- and 2D-NMR spectroscopic studies. The
      absolute configuration of compound 6 was established using CD spectroscopy.
      Several derivatives (14-20) were prepared from the sesquiterpene 13. Most of the
      sesquiterpenoids were tested for anti-HIV activity, but only compound 1 was found
      to be active. 

PMID- 25057906
TI  - Red, green, blue (RGB) electrochromic fibers for the new smart color change
      fabrics.
AB  - These fibers are prepared using stainless steel wires (SSWs) as a substrate.
      Three kinds of electrochromic materials (poly(3,4-ethylenedioxythiophene), poly(3
      methylthiophene), and poly(2,5-dimethoxyaniline)) are quickly deposited on the
      surface of the SSWs by electrochemical polymerization. A polymer gel electrolyte
      is then coated onto the electrochromic layer, and another finer stainless steel
      wire is twisted on, in succession. The obvious RGB colors and gradient color
      phenomenon from gray to dark blue are observed by the naked eye besides color
      changes from oxidized to reduced states. Moreover, these electrochromic fibers
      have very short response times (millisecond scale), excellent flexibility, and
      good structural stability even though the bending and folding occurred. They also
      can be implanted into fabrics to achieve more color combinations through
      regulating the voltages and parallel connection of different circuits. 

PMID- 25057905
TI  - Intrapopulation genome size variation in D. melanogaster reflects life history
      variation and plasticity.
AB  - We determined female genome sizes using flow cytometry for 211 Drosophila
      melanogaster sequenced inbred strains from the Drosophila Genetic Reference
      Panel, and found significant conspecific and intrapopulation variation in genome
      size. We also compared several life history traits for 25 lines with large and 25
      lines with small genomes in three thermal environments, and found that genome
      size as well as genome size by temperature interactions significantly correlated
      with survival to pupation and adulthood, time to pupation, female pupal mass, and
      female eclosion rates. Genome size accounted for up to 23% of the variation in
      developmental phenotypes, but the contribution of genome size to variation in
      life history traits was plastic and varied according to the thermal environment.
      Expression data implicate differences in metabolism that correspond to genome
      size variation. These results indicate that significant genome size variation
      exists within D. melanogaster and this variation may impact the evolutionary
      ecology of the species. Genome size variation accounts for a significant portion
      of life history variation in an environmentally dependent manner, suggesting that
      potential fitness effects associated with genome size variation also depend on
      environmental conditions. 

PMID- 25057907
TI  - A single-chain magnet based on {Co(II)4} complexes and azido/picolinate ligands.
AB  - A new homonuclear single-chain magnet self-assembles as a one-dimensional
      coordination network of defective dicubane {Co(II)4} complexes linked by single
      Co(II) ions with the assistance of azido and picolinate ligands. Dominating
      intrachain ferromagnetic interactions, intrinsic Ising-like Co(II) anisotropy,
      and negligible interchain magnetic interactions lead to a thermally activated
      relaxation time of the magnetization below 8 K. Two thermally activated regimes
      above and below 3.5 K are observed with the following energy barriers:
      Delta(tau1)/k(B) = 66 K (tau0 = 3.7 * 10(-11) s) and Delta(tau2)/k(B) = 51 K
      (tau0 = 2.3 * 10(-9) s), respectively. The difference between the two energy
      barriers of the relaxation time, 15 K, agrees well with the experimental energy,
      Delta(xi), to create a domain wall along the chain.

PMID- 25057908
TI  - Mechanistic insights in glycation-induced protein aggregation.
AB  - Protein glycation causes loss-of-function through a process that has been
      associated with several diabetic-related diseases. Additionally, glycation has
      been hypothesized as a promoter of protein aggregation, which could explain the
      observed link between hyperglycaemia and the development of several aggregating
      diseases. Despite its relevance in a range of diseases, the mechanism through
      which glycation induces aggregation remains unknown. Here we describe the
      molecular basis of how glycation is linked to aggregation by applying a variety
      of complementary techniques to study the nonenzymatic glycation of hen lysozyme
      with ribose (ribosylation) as the reducing carbohydrate. Ribosylation involves a
      chemical multistep conversion that induces chemical modifications on lysine side
      chains without altering the protein structure, but changing the protein charge
      and enlarging its hydrophobic surface. These features trigger lysozyme native
      like aggregation by forming small oligomers that evolve into bigger insoluble
      particles. Moreover, lysozyme incubated with ribose reduces the viability of SH
      SY5Y neuroblastoma cells. Our new insights contribute toward a better
      understanding of the link between glycation and aggregation. 

PMID- 25057909
TI  - Photophysics of bis-bipyridyl nitro complexes of ruthenium(II) with pyridine
      ligands: substituent effects.
AB  - Emission, excitation spectra, quantum yields, and emission lifetimes are reported
      for the mixed ligand, bis-(2,2'-bipyridine)ruthenium(II) complexes cis
      [Ru(bpy)2(L)(NO2)](+) with 4-substituted pyridines as ligands L [isonicotinamide
      (isnc), 4,4'-bipyridine (bipy), pyridine (py), 4-phenylpyridine (phpy), 1,2-bis(4
      pyridyl)ethane (bpa), 4-picoline (mepy), 4-aminopyridine (apy), and 4
      dimethylaminopyridine (ampy)] in EtOH-MeOH, 4:1 (V:V), at 77 K. Radiative, k(r),
      and nonradiative, k(nr), decay rate constants were determined for the series of
      complexes, and a linear dependence of ln k(nr) on E00, with E00 as the 0-0 energy
      gap determined by emission spectral fitting, was obtained with a slope of -(3.35
      +/- 0.23) * 10(-4) cm(-1). A linear correlation of E00 for cis
      [Ru(bpy)2(L)(NO2)](+) complexes and Hammett substituent constant sigma(p) is
      found.

PMID- 25057910
TI  - Arginase inhibition ameliorates hepatic metabolic abnormalities in obese mice.
AB  - OBJECTIVES: We examined whether arginase inhibition influences hepatic metabolic
      pathways and whole body adiposity in diet-induced obesity. METHODS AND RESULTS:
      After obesity induction by a high fat diet (HFD), mice were fed either the HFD or
      the HFD with an arginase inhibitor, Nomega-hydroxy-nor-L-arginine (nor-NOHA). Nor
      NOHA significantly prevented HFD-induced increases in body, liver, and visceral
      fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA
      treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in
      vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice
      and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in
      lipid metabolism. Expression of phosphorylated 5' AMPK-activated protein kinase
      alpha was increased by arginase inhibition in the mouse livers and HepG2 cells.
      CONCLUSIONS: Arginase inhibition ameliorated obesity-induced hepatic lipid
      abnormalities and whole body adiposity, possibly as a result of increased hepatic
      NO production and subsequent activation of metabolic pathways involved in hepatic
      triglyceride metabolism and mitochondrial function.

PMID- 25057911
TI  - IrSPI, a tick serine protease inhibitor involved in tick feeding and Bartonella
      henselae infection.
AB  - Ixodes ricinus is the most widespread and abundant tick in Europe, frequently
      bites humans, and is the vector of several pathogens including those responsible
      for Lyme disease, Tick-Borne Encephalitis, anaplasmosis, babesiosis and
      bartonellosis. These tick-borne pathogens are transmitted to vertebrate hosts via
      tick saliva during blood feeding, and tick salivary gland (SG) factors are likely
      implicated in transmission. In order to identify such tick factors, we
      characterized the transcriptome of female I. ricinus SGs using next generation
      sequencing techniques, and compared transcriptomes between Bartonella henselae
      infected and non-infected ticks. High-throughput sequencing of I. ricinus SG
      transcriptomes led to the generation of 24,539 isotigs. Among them, 829 and 517
      transcripts were either significantly up- or down-regulated respectively, in
      response to bacterial infection. Searches based on sequence identity showed that
      among the differentially expressed transcripts, 161 transcripts corresponded to
      nine groups of previously annotated tick SG gene families, while the others
      corresponded to genes of unknown function. Expression patterns of five selected
      genes belonging to the BPTI/Kunitz family of serine protease inhibitors, the tick
      salivary peptide group 1 protein, the salp15 super-family, and the arthropod
      defensin family, were validated by qRT-PCR. IrSPI, a member of the BPTI/Kunitz
      family of serine protease inhibitors, showed the highest up-regulation in SGs in
      response to Bartonella infection. IrSPI silencing impaired tick feeding, as well
      as resulted in reduced bacterial load in tick SGs. This study provides a
      comprehensive analysis of I. ricinus SG transcriptome and contributes significant
      genomic information about this important disease vector. This in-depth knowledge
      will enable a better understanding of the molecular interactions between ticks
      and tick-borne pathogens, and identifies IrSPI, a candidate to study now in
      detail to estimate its potentialities as vaccine against the ticks and the
      pathogens they transmit. 

PMID- 25057912
TI  - Lactoferrin deficiency promotes colitis-associated colorectal dysplasia in mice.
AB  - Nonresolving inflammatory processes affect all stages of carcinogenesis.
      Lactoferrin, a member of the transferrin family, is involved in the innate immune
      response and anti-inflammatory, anti-microbial, and anti-tumor activities. We
      previously found that lactoferrin is significantly down-regulated in specimens of
      nasopharyngeal carcinoma (NPC) and negatively associated with tumor progression,
      metastasis, and prognosis of patients with NPC. Additionally, lactoferrin
      expression levels are decreased in colorectal cancer as compared with normal
      tissue. Lactoferrin levels are also increased in the various phases of
      inflammation and dysplasia in an azoxymethane-dextran sulfate sodium (AOM-DSS)
      model of colitis-associated colon cancer (CAC). We thus hypothesized that the
      anti-inflammatory function of lactoferrin may contribute to its anti-tumor
      activity. Here we generated a new Lactoferrin knockout mouse model in which the
      mice are fertile, develop normally, and display no gross morphological
      abnormalities. We then challenged these mice with chemically induced intestinal
      inflammation to investigate the role of lactoferrin in inflammation and cancer
      development. Lactoferrin knockout mice demonstrated a great susceptibility to
      inflammation-induced colorectal dysplasia, and this characteristic may be related
      to inhibition of NF-kappaB and AKT/mTOR signaling as well as regulation of cell
      apoptosis and proliferation. Our results suggest that the protective roles of
      lactoferrin in colorectal mucosal immunity and inflammation-related malignant
      transformation, along with a deficiency in certain components of the innate
      immune system, may lead to serious consequences under conditions of inflammatory
      insult. 

PMID- 25057913
TI  - A micro-Raman study of live, single red blood cells (RBCs) treated with AgNO3
      nanoparticles.
AB  - Silver nanoparticles (Ag NPs) are known to exhibit broad antimicrobial activity.
      However, such activity continues to raise concerns in the context of the
      interaction of such NPs with biomolecules. In a physiological environment NPs
      interact with individual biological cells either by penetrating through the cell
      membrane or by adhering to the membrane. We have explored the interaction of Ag
      NPs with single optically-trapped, live erythrocytes (red blood cells, RBCs)
      using Raman Tweezers spectroscopy. Our experiments reveal that Ag NPs induce
      modifications within an RBC that appear to be irreversible. In particular we are
      able to identify that the heme conformation in an RBC transforms from the usual R
      state (oxy-state) to the T-state (deoxy-state). We rationalize our observations
      by proposing a model for the nanoparticle cytotoxicity pathway when the NP size
      is larger than the membrane pore size. We propose that the interaction of Ag NPs
      with the cell surface induces damage brought about by alteration of intracellular
      pH caused by the blockage of the cell membrane transport. 

PMID- 25057915
TI  - A systematic review of peripheral nerve interventional treatments for chronic
      headaches.

PMID- 25057916
TI  - Surgical Technique for Whistler Deformity Repair in Bilateral Cleft Lip Patients:
      An Anthropometric Study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the surgical outcome of
      secondary bilateral cleft lips after using a surgical technique for whistler
      deformity repair. DESIGN: A prospective cohort study of one surgeon's outcome of
      38 consecutive performed bilateral whistler deformity repairs was conducted.
      SETTING: Data from the Outreach Surgical Center Program, Lima, Peru, were used.
      PATIENTS: Thirty-eight patients with lip deformity related to unsatisfactory
      bilateral cleft lip repair were operated on using the proposed surgical technique
      since 2008. All these patients met the study criterion of having anthropometric
      measurements performed at least 1 year postoperatively. MAIN OUTCOME MEASURES:
      Measurement of lip height, lip width, vermilion height, cupid bow, and nasal base
      width was performed at the right and left side of the lip, preoperatively and at
      least 1 year postoperatively. ANALYSIS: The matched pair t test analyses were
      performed when the assumptions required were met. When the normality assumption
      was not met, the Wilcoxon signed rank test, a nonparametric test was used to
      assess the statistical significance of differences between the studied sample and
      control group. RESULTS: The study found statistically significant differences
      between the preoperatory and control groups in most of the lip measurements. In
      addition, we have found statistically significant differences between the
      preoperatory and postoperatory groups in most of the anthropometric lip
      measurements, in favor of the second group, after lip repair using the proposed
      technique and measured at least 1 year postoperatively. CONCLUSIONS: The findings
      suggest that the proposed technique is a good alternative to address the whistler
      deformity related to the bilateral cleft lip primary repair.

PMID- 25057914
TI  - Acceptance of vaccinations in pandemic outbreaks: a discrete choice experiment.
AB  - BACKGROUND: Preventive measures are essential to limit the spread of new viruses;
      their uptake is key to their success. However, the vaccination uptake in pandemic
      outbreaks is often low. We aim to elicit how disease and vaccination
      characteristics determine preferences of the general public for new pandemic
      vaccinations. METHODS: In an internet-based discrete choice experiment (DCE) a
      representative sample of 536 participants (49% participation rate) from the Dutch
      population was asked for their preference for vaccination programs in
      hypothetical communicable disease outbreaks. We used scenarios based on two
      disease characteristics (susceptibility to and severity of the disease) and five
      vaccination program characteristics (effectiveness, safety, advice regarding
      vaccination, media attention, and out-of-pocket costs). The DCE design was based
      on a literature review, expert interviews and focus group discussions. A panel
      latent class logit model was used to estimate which trade-offs individuals were
      willing to make. RESULTS: All above mentioned characteristics proved to influence
      respondents' preferences for vaccination. Preference heterogeneity was
      substantial. Females who stated that they were never in favor of vaccination made
      different trade-offs than males who stated that they were (possibly) willing to
      get vaccinated. As expected, respondents preferred and were willing to pay more
      for more effective vaccines, especially if the outbreak was more serious (?6-?39
      for a 10% more effective vaccine). Changes in effectiveness, out-of-pocket costs
      and in the body that advises the vaccine all substantially influenced the
      predicted uptake. CONCLUSIONS: We conclude that various disease and vaccination
      program characteristics influence respondents' preferences for pandemic
      vaccination programs. Agencies responsible for preventive measures during
      pandemics can use the knowledge that out-of-pocket costs and the way advice is
      given affect vaccination uptake to improve their plans for future pandemic
      outbreaks. The preference heterogeneity shows that information regarding
      vaccination needs to be targeted differently depending on gender and willingness
      to get vaccinated.

PMID- 25057917
TI  - Clinical Experience With the Combination of a Biceps Femoris Muscle Turnover Flap
      and a Posterior Thigh Fasciocutaneous Hatchet Flap for the Reconstruction of
      Ischial Pressure Ulcers.
AB  - BACKGROUND: The reconstruction of ischial pressure ulcers is problematic because
      of the distinctive anatomical properties of the region and high recurrence rates.
      To date, no single technique has been proven to be effective in reducing
      recurrence of the ulcers. We present our experience with the combination of a
      biceps femoris muscle turnover flap and a posterior thigh fasciocutaneous hatchet
      flap and discuss the long-term results. METHODS: A retrospective clinical
      analysis of 15 patients with grade 4 ischial pressure ulcers reconstructed with
      biceps femoris muscle turnover flaps and laterally based posterior thigh
      fasciocutaneous hatchet flaps was carried out between January 2010 and January
      2013. Debridement and reconstruction of the ulcers were accomplished in a single
      stage. The posterior thigh fasciocutaneous flap was elevated in a hatchet style.
      The long and/or short head of the biceps femoris muscle were dissected from their
      insertions, turned over on their major pedicles, and their distal portions were
      used to obliterate the cavitary defect. The skin defect over the muscles was
      covered by the fasciocutaneous hatchet flap. The average age of the patients was
      42.6 years and the mean follow-up time was 27.2 months. RESULTS: Three patients
      had the following early postoperative complications: hematoma, suture dehiscence,
      and the necrosis of the short head of biceps muscle. Only 1 patient had a
      recurrent ulcer 15 months after surgery, which was treated with debridement and
      the readvancement of the fasciocutaneous flap. The overall recurrence rate was
      6.6%. CONCLUSIONS: The biceps femoris muscle turnover flap combined with the
      posterior thigh fasciocutaneous hatchet flap is a worthwhile option to consider
      for the reconstruction of ischial pressure ulcers and this technique produces
      favorable results in terms of the lack of recurrence and complications. The use
      of the muscle and fasciocutaneous tissue as 2 different flaps, which have
      different roles in the early and late postoperative period, reduces the
      recurrence rate.

PMID- 25057918
TI  - Tissue Expander Reconstruction After Total Skin-Sparing Mastectomy: Defining the
      Effects of Coverage Technique on Nipple/Areola Preservation.
AB  - BACKGROUND: Total skin-sparing mastectomy (TSSM) has become increasingly frequent
      in recent years, as inclusion criteria continue to expand. Options for tissue
      expander coverage in these patients include complete submuscular tissue expander
      coverage and acellular dermal matrix (ADM)-assisted coverage. This study compares
      both techniques with regard to relevant outcomes, during a recent 1-year period
      at our institution. METHODS: All women undergoing TSSM and immediate expander
      placement between January 2012 and January 2013 were prospectively tracked.
      Patient demographics, expander coverage type, adjuvant treatment, length and
      characteristics of expansion, and incidence of complications were analyzed.
      RESULTS: In 1 year, 127 patients underwent TSSM on 202 breasts. Overall, 113
      expanders underwent submuscular coverage, and 89 underwent ADM-assisted coverage.
      Mean intraoperative fill volume was 52 mL in the submuscular cohort and 205 mL in
      the ADM cohort (P = 0.0001). Mean tissue expander size was 404 mL in the
      submuscular cohort and 454 mL in the ADM cohort (P = 0.0002). chi analysis
      demonstrated no differences between the cohorts in incidence of complications,
      including partial/complete nipple necrosis. CONCLUSIONS: The use of ADM for
      expander coverage after TSSM allowed for greater initial expander fill. With
      large and ptotic breasts, this allows for reduced incidence of skin folds in the
      preserved breast skin pocket, and greater control over final nipple position, as
      the amount of loose, mobile skin is reduced by the greater initial fill. The
      safety profile of ADM use after TSSM is equivalent to that of submuscular
      coverage, with no differences in partial or complete nipple necrosis.

PMID- 25057919
TI  - Lipotransfer: the potential from bench to bedside.

PMID- 25057923
TI  - Highly stable and reversible lithium storage in SnO2 nanowires surface coated
      with a uniform hollow shell by atomic layer deposition.
AB  - SnO2 nanowires directly grown on flexible substrates can be a good electrode for
      a lithium ion battery. However, Sn-based (metal Sn or SnO2) anode materials
      always suffer from poor stability due to a large volume expansion during cycling.
      In this work, we utilize atomic layer deposition (ALD) to surface engineer SnO2
      nanowires, resulting in a new type of hollowed SnO2-in-TiO2 wire-in-tube
      nanostructure. This structure has radically improved rate capability and cycling
      stability compared to both bare SnO2 nanowires and solid SnO2@TiO2 core-shell
      nanowire electrodes. Typically a relatively stable capacity of 393.3 mAh/g has
      been achieved after 1000 charge-discharge cycles at a current density of 400
      mA/g, and 241.2 mAh/g at 3200 mA/g. It is believed that the uniform hollow TiO2
      shell provides stable surface protection and the appropriate-sized gap
      effectively accommodates the expansion of the interior SnO2 nanowire. This ALD
      enabled method should be general to many other battery anode and cathode
      materials, providing a new and highly reproducible and controllable technique for
      improving battery performance. 

PMID- 25057921
TI  - Novel small molecule XPO1/CRM1 inhibitors induce nuclear accumulation of TP53,
      phosphorylated MAPK and apoptosis in human melanoma cells.
AB  - XPO1/CRM1 is a key nuclear exporter protein that mediates translocation of
      numerous cellular regulatory proteins. We investigated whether XPO1 is a
      potential therapeutic target in melanoma using novel selective inhibitors of
      nuclear export (SINE). In vitro effects of SINE on cell growth and apoptosis were
      measured by MTS assay and flow cytometry [Annexin V/propidium iodide (PI)],
      respectively in human metastatic melanoma cell lines. Immunoblot analysis was
      used to measure nuclear localization of key cellular proteins. The in vivo
      activity of oral SINE was evaluated in NOD/SCID mice bearing A375 or CHL-1 human
      melanoma xenografts. SINE compounds induced cytostatic and pro-apoptotic effects
      in both BRAF wild type and mutant (V600E) cell lines at nanomolar concentrations.
      The cytostatic and pro-apoptotic effects of XPO1 inhibition were associated with
      nuclear accumulation of TP53, and CDKN1A induction in the A375 cell line with
      wild type TP53, while pMAPK accumulated in the nucleus regardless of TP53 status.
      The orally bioavailable KPT-276 and KPT-330 compounds significantly inhibited
      growth of A375 (p<0.0001) and CHL-1 (p = 0.0087) human melanoma cell lines in
      vivo at well tolerated doses. Inhibition of XPO1 using SINE represents a
      potential therapeutic approach for melanoma across cells with diverse molecular
      phenotypes by promoting growth inhibition and apoptosis.

PMID- 25057922
TI  - Network analysis of breast cancer progression and reversal using a tree-evolving
      network algorithm.
AB  - The HMT3522 progression series of human breast cells have been used to discover
      how tissue architecture, microenvironment and signaling molecules affect breast
      cell growth and behaviors. However, much remains to be elucidated about malignant
      and phenotypic reversion behaviors of the HMT3522-T4-2 cells of this series. We
      employed a "pan-cell-state" strategy, and analyzed jointly microarray profiles
      obtained from different state-specific cell populations from this progression and
      reversion model of the breast cells using a tree-lineage multi-network inference
      algorithm, Treegl. We found that different breast cell states contain distinct
      gene networks. The network specific to non-malignant HMT3522-S1 cells is
      dominated by genes involved in normal processes, whereas the T4-2-specific
      network is enriched with cancer-related genes. The networks specific to various
      conditions of the reverted T4-2 cells are enriched with pathways suggestive of
      compensatory effects, consistent with clinical data showing patient resistance to
      anticancer drugs. We validated the findings using an external dataset, and showed
      that aberrant expression values of certain hubs in the identified networks are
      associated with poor clinical outcomes. Thus, analysis of various reversion
      conditions (including non-reverted) of HMT3522 cells using Treegl can be a good
      model system to study drug effects on breast cancer. 

PMID- 25057924
TI  - Rhodamine 101-graphene oxide composites in aqueous solution: the fluorescence
      quenching process of rhodamine 101.
AB  - The interaction of rhodamine 101 (Rh101) with graphene oxide (GO) in aqueous
      dispersion was examined using advanced spectroscopic techniques. Rh101-GO
      composites in water were easily prepared by mixing an aqueous solution of both
      components since GO sheets interacted with the cationic dyes via pi-pi and
      electrostatic cooperative interactions. In the composites, the fluorescence of
      Rh101, which was a well-known laser dye with a high fluorescence quantum yield,
      could be efficiently quenched by GO. The quenching mechanism of Rh101 by GO
      sheets was evaluated by the Stern-Volmer (SV) equation and the time-resolved
      fluorescence studies. The results revealed that the fluorescence quenching of
      Rh101 by GO in the aqueous dispersion is due to the static quenching mechanism.
      The formation of the Rh101-GO composites at various pH values was
      spectroscopically monitored, and the spectroscopic results revealed that the
      composites were formed at the pH values studied except in the strong acidic media
      (pH ~ 2). The interaction of Rh101 with GO in aqueous solution was
      spectroscopically followed in the presence of SDS (sodium dodecyl sulphate) at
      the surfactant concentrations above and below the CMC (critical micelle
      concentration). The fluorescence studies revealed that the fluorescence of Rh101
      in the aqueous solution remarkably increased at the surfactant concentration
      forming the micelle of SDS. 

PMID- 25057925
TI  - Regulation of endothelial cell inflammation and lung polymorphonuclear lymphocyte
      infiltration by transglutaminase 2.
AB  - We addressed the role of transglutaminase 2 (TG2), a calcium-dependent enzyme
      that catalyzes cross-linking of proteins, in the mechanism of endothelial cell
      (EC) inflammation and lung polymorphonuclear lymphocyte (PMN) infiltration.
      Exposure of EC to thrombin, a procoagulant and proinflammatory mediator, resulted
      in activation of the transcription factor nuclear factor kappaB (NF-kappaB) and
      its target genes, vascular cell adhesion molecule 1, monocyte chemotactic protein
      1, and interleukin 6. RNAi knockdown of TG2 inhibited these responses. Analysis
      of NF-kappaB activation pathway showed that TG2 knockdown was associated with
      inhibition of thrombin-induced DNA binding as well as serine phosphorylation of
      RelA/p65, a crucial event that controls transcriptional capacity of the DNA-bound
      RelA/p65. These results implicate an important role for TG2 in mediating EC
      inflammation by promoting DNA-binding and transcriptional activity of RelA/p65.
      Because thrombin is released in high amounts during sepsis, and its concentration
      is elevated in plasma and lavage fluids of patients with acute respiratory
      distress syndrome, we determined the in vivo relevance of TG2 in a mouse model of
      sepsis-induced lung PMN recruitment. A marked reduction in NF-kappaB activation,
      adhesion molecule expression, and lung PMN sequestration was observed in TG2
      knockout mice compared with wild-type mice exposed to endotoxemia. Together,
      these results identify TG2 as an important mediator of EC inflammation and lung
      PMN sequestration associated with intravascular coagulation and sepsis. 

PMID- 25057926
TI  - Extracellular signal-regulated kinase-mammalian target of rapamycin signaling and
      forkhead-box transcription factor 3a phosphorylation are involved in
      testosterone's effect on severe burn injury in a rat model.
AB  - BACKGROUND: Testosterone and androgen receptor agonists have been known for a
      long time to prevent or reverse muscle wasting in burn injury patients, but the
      exact molecular mechanisms are not clear. OBJECTIVE: To investigate the
      underlying molecular mechanisms of testosterone in severely burned rats. METHODS:
      Severe burn injuries were induced by immersing the back of the rat in 100 
      degrees C water for 12 s. Rats were treated for 14 days with vehicle (burn group)
      or a physiological replacement dose of testosterone (B + T group) immediately
      after injury. Gene and protein expressions were assessed by real-time polymerase
      chain reaction and Western blot. RESULTS: Testosterone improved glucose
      metabolism, reduced body weight loss, and attenuated tibialis anterior muscle
      mass loss and muscle protein breakdown. In rat tibialis anterior muscle,
      testosterone positively regulated the insulin-sensitive glucose transporters
      Glut3 and Glut4 genes and glycogen synthase 1 protein. These changes would be
      expected to improve glucose metabolism and nutrient availability in skeletal
      muscle. Administration of testosterone negatively regulated atrogin 1 (Fbxo32) by
      increasing total and phosphorylated Foxo3a (forkhead-box transcription factor 3a)
      levels and positively regulated the expression of the mammalian target of
      rapamycin (mTOR) and its downstream proteins p70S6 and S6 through mTOR
      extracellular signal-regulated kinase phosphorylation. CONCLUSIONS: RESULTS
      suggested that testosterone might regulate skeletal muscle glucose and protein
      metabolism following burn injury in part by affecting extracellular signal
      regulated kinase-mTOR signaling and Foxo3a levels.

PMID- 25057927
TI  - Programmed cell death receptor ligand 1 modulates the regulatory T cells'
      capacity to repress shock/sepsis-induced indirect acute lung injury by recruiting
      phosphatase SRC homology region 2 domain-containing phosphatase 1.
AB  - We recently reported that adoptively transferred (AT) exogenous CD4+ CD25+
      regulatory T cells (Tregs) to wild-type (WT) mice can directly act to repress
      shock/sepsis-induced experimental indirect acute lung injury (iALI), and this is
      mediated in part by programmed cell death receptor 1 (PD-1). In this study, we
      further determine whether recipient mouse lacking PD-L1, one of the primary
      ligands for PD-1, contributes to the manipulation of the Tregs' capacity to
      repress lung injury. To do this, Tregs isolated from the spleen of WT mice were
      AT into PD-L1 mice subjected to hemorrhagic shock and subsequent to cecal
      ligation and puncture to induce iALI. Samples were collected for analyses 24 h
      after cecal ligation and puncture. We found that in PD-L1-recipient mice, AT WT
      Tregs lost the ability to reverse the development of iALI seen in WT recipient
      mice (i.e., no reduction of lung injury indices assessed by histology and
      vascular leakage, failure to decrease the lung neutrophil influx [myeloperoxidase
      activity], or the rise in lung apoptosis [caspase 3 activity]). Also, a
      significant increase in interleukin 1beta (IL-1beta) and keratinocyte-derived
      chemokine, but no changes in IL-6, IL-10, and IL-17A levels in lung tissues were
      seen in these mice compared with iALI mice without AT of Tregs. Furthermore, we
      noted that the lung tissue tyrosine phosphatase Src homology region 2 domain
      containing phosphatase 1 (SHP-1), but not SHP-2, was activated with the AT of
      Tregs in PD-L1(-/-) iALI mice. Finally, through local depletion of CD4+ T cells
      or CD25+ (Tregs) in the lung, prior to inducing iALI, we found that SHP-1
      activation was associated with the loss of Tregs' protective effects in vivo.
      Collectively, our data reveal that PD-L1 is a critical modulator of Tregs'
      ability to suppress iALI, and this appears to involve SHP-1 activation.

PMID- 25057929
TI  - No correlation between remifentanil blood, cerebrospinal fluid and cerebral
      extracellular fluid levels and TCI prediction: a pharmacokinetic study.
AB  - BACKGROUND: The aims of this paper were to elucidate the difference in
      concentration among remifentanil blood, cerebrospinal fluid and cerebral
      extracellular fluid levels, and to verify the presumable existence of a
      correlation between arterial and cerebral remifentanil. We used brain
      microdialysis to shed light on this aspect of the pharmacokinetic and to
      correlate these findings with Minto's model. METHODS: The study population was
      formed by 9 patients scheduled for elective intracranial surgery for cerebral
      supratentorial neoplasia. All patients received general anaesthetic; 100
      microliters of dialysate were collected. Furthermore, arterial blood samples of 3
      mL each were collected, respectively one at the beginning and one at the end of
      the sampling period. We determined the concentration of remifentanil and its main
      metabolite, remifentanil acid, in the blood and in the brain. The predictive
      performance of the Minto pharmacokinetic parameter set was evaluated by examining
      the performance error. RESULTS: The mean Performance Error was -45.13% (min 
      21.80, max -88.75) for the first series of arterial samples, -38.29% (min -6.57,
      max -79.17) for the second one and 67.73% (min 7, max -93.12) for the extra
      cellular fluid sample. The concentration of remifentanil set pumps was correlated
      with blood concentration for both series of samples. Neither the set
      concentration, nor the arterial samples were correlated with extra cellular fluid
      values. CONCLUSION: There was a wide interindividual variability with regard both
      to blood and cerebral remifentanil concentration. Moreover, the ratio between
      arterial blood and cerebral remifentanil was not consistent among our patients in
      spite of a stable infusion rate of remifentanil; at the end we found a trend of
      over prediction in the ratio between the various compartments examined.

PMID- 25057928
TI  - Drosophila eyes absent is required for normal cone and pigment cell development.
AB  - In Drosophila, development of the compound eye is orchestrated by a network of
      highly conserved transcriptional regulators known as the retinal determination
      (RD) network. The retinal determination gene eyes absent (eya) is expressed in
      most cells within the developing eye field, from undifferentiated retinal
      progenitors to photoreceptor cells whose differentiation begins at the
      morphogenetic furrow (MF). Loss of eya expression leads to an early block in
      retinal development, making it impossible to study the role of eya expression
      during later steps of retinal differentiation. We have identified two new
      regulatory regions that control eya expression during retinal development. These
      two enhancers are necessary to maintain eya expression anterior to the MF (eya
      IAM) and in photoreceptors (eya-PSE), respectively. We find that deleting these
      enhancers affects developmental events anterior to the MF as well as retinal
      differentiation posterior to the MF. In line with previous results, we find that
      reducing eya expression anterior to the MF affects several early steps during
      early retinal differentiation, including cell cycle arrest and expression of the
      proneural gene ato. Consistent with previous observations that suggest a role for
      eya in cell proliferation during early development we find that deletion of eya
      IAM leads to a marked reduction in the size of the adult retinal field. On the
      other hand, deletion of eya-PSE leads to defects in cone and pigment cell
      development. In addition we find that eya expression is necessary to activate
      expression of the cone cell marker Cut and to regulate levels of the Hedgehog
      pathway effector Ci. In summary, our study uncovers novel aspects of eya-mediated
      regulation of eye development. The genetic tools generated in this study will
      allow for a detailed study of how the RD network regulates key steps in eye
      formation. 

PMID- 25057930
TI  - Enhanced visual acuity with echogenic needles in ultrasound-guided axillary
      brachial plexus block: a randomized, comparative, observer-blinded study.
AB  - BACKGROUND: We prospectively evaluated the effect of insertion angle on the
      visibility of echogenic and nonechogenic needles in phantoms and in axillary
      nerve blocks in patients. METHODS: Conventional and echogenic needles were
      studied in phantoms at insertion angles of 0-30 degrees , 30-45 degrees , and >=
      45 degrees . Operators rated comfort and image quality during the procedure and
      experts blinded to the needle groups randomly analyzed videos for tip and shaft
      visibility, surrounding tissue visibility, sharpness of the needle surface, and
      percentage of time with the needle completely visible. Patients scheduled for
      axillary nerve block were prospectively enrolled in the clinical study. Needle
      insertion angles were 0-30 degrees  for the median nerve approach, 30-45 degrees 
      for the radial nerve, and >= 45 degrees  for the musculocutaneous nerve. The same
      needle parameters were analyzed during the procedure and on videos. RESULTS:
      Physician comfort and image quality were significantly better for echogenic
      needles for phantoms and patients at 30-45 degrees  and >= 45 degrees  insertion
      angles. Needle tip and shaft visibility at 30-45 degrees  and >= 45 degrees 
      insertion angles in phantoms and for the musculocutaneous nerve in patients were
      significantly improved, as well as the percentage with complete needle
      visualization during the procedure. Tissue visibility and needle sharpness were
      significantly superior for conventional needles. There were no differences
      concerning block parameters and adverse events. CONCLUSION: Needles with enhanced
      echogenicity improved physician comfort, image quality, needle visibility, and
      visualization time of the needle during ultrasound-guided procedures in phantoms
      and axillary nerve blocks using insertion angles of 30-45 degrees  and >= 45
      degrees .

PMID- 25057931
TI  - Risk of perioperative seizures in patients undergoing craniotomy with
      intraoperative brain mapping.
AB  - BACKGROUND: The identification of risk factors associated with perioperative
      seizures would be of great benefit to the anesthesiologist in managing brain
      tumor patients undergoing craniotomy with intraoperative brain mapping. METHODS:
      A series of 316 supratentorial craniotomies for tumor resection, in which
      intraoperative brain mapping was used, were analyzed. From January 2005 to
      December 2010 the occurrence of intraoperative and immediate postoperative
      clinical seizures was prospectively recorded into a database. Demographic data,
      tumor characteristics, preoperative seizure control, intraoperative events and
      anesthetic management were evaluated as risk factors for intraoperative clinical
      seizures. Additionally, the association between intraoperative clinical seizures
      and immediate postoperative seizures was evaluated. In order to determine the
      best predictors of intraoperative and immediate postoperative clinical seizures,
      a multivariable analysis by logistic regression was performed. RESULTS: Younger
      age, location of the tumor in the frontal and parietal lobe, brain mapping
      conducted under general anesthesia and non physiologic values of arterial carbon
      dioxide (PaCO2) during brain mapping were independent positive risk factors for
      the development of intraoperative clinical seizures. Location of tumor in the
      frontal lobe, antiepileptic polytherapy, intraoperative seizures requiring
      pharmacologic treatment during brain mapping, and blood on postoperative CT scan
      were independent positive risk factors for the development of immediate
      postoperative seizures. CONCLUSION: Clinical seizures are common intraoperative
      and postoperative complications of supratentorial craniotomies with
      intraoperative brain mapping. The identification of those patients at higher risk
      of seizures may guide intraoperative and postoperative medical management.

PMID- 25057932
TI  - Real-time ultrasound guided percutaneous dilatational tracheostomy with and
      without bronchoscopic control: an observational study.
AB  - BACKGROUND: Real-time ultrasound guidance may enable precise introducer needle
      and guidewire insertion during percutaneous dilatational tracheostomy (PDT).
      However, the safety of PDT done solely under ultrasound guidance has not been
      compared to additional bronchoscopic confirmation. We aimed to compare the
      efficacy, incidence of complications and procedural times of real-time ultrasound
      guided PDTs done with and without bronchoscopic confirmation. METHODS: We
      analysed all bedside PDTs performed over an 18 month period. On transverse view,
      the introducer needle was inserted under real time guidance into the chosen
      interspace. The interspace of guidewire entry was confirmed on longitudinal view.
      In the bronchoscope group, needle and guidewire position within the tracheal
      lumen were confirmed by bronchoscopy. RESULTS: We performed 177 PDTs under
      ultrasound guidance during the study period - 95 with and 82 without
      bronchoscopic confirmation. The introducer needle was inserted at the desired
      level on the first attempt in 81.4% of instances with no difference between
      groups (77.9% vs. 85.4%, P=0.6). Introducer needle entry between the first and
      third tracheal cartilages did not differ between groups (90.5% vs. 92.7%, P=0.6).
      Procedural times were longer in the bronchoscope group (13.9 min vs. 10.7 min,
      P<0.0001). There were more episodes of fall in oxygen saturation below 90% in the
      bronchoscope group (16.8% vs. 3.7%, P=0.006). Minor bleeding occurred in 6.2% of
      cases and did not differ between groups. CONCLUSION: Ultrasound guidance for PDT
      may be equally safe, even without bronchoscopic confirmation; the incidence of
      hypoxic episodes may be less and the procedure can be performed in less time.

PMID- 25057933
TI  - Competence for transcranial color-coded Duplex sonography is rapidly acquired.
AB  - BACKGROUND: Transcranial color-coded Duplex sonography (TCCD) is a non-invasive
      bedside tool with broad diagnostic potential in the intensive care setting.
      Implementation of TCCD requires repeated reliable measurements of flow velocities
      despite data acquisition by multiple operators with varying experience. Thus the
      learning curve of TCCD and agreement of measurements between experienced and
      inexperienced operators is of great interest and unstudied so far. METHODS: Six
      untrained ICU-residents and 2 trained operators participated and performed TCCD
      examinations of the mean cerebral artery (MCA) in 10 volunteers. Measurements of
      the residents were compared to the according measurements of the trained
      operators. Operators were either actively supervised during their first five
      examinations or performed the examinations without supervision. RESULTS: A total
      of 480 measurements were obtained. Mean flow velocity (MFV) did not differ
      significantly between trained and untrained operators in the two groups (P=0.78
      in not-supervised and P=0.82 in supervised group). We found a favorable learning
      curve in both groups (ICC 0.8, CI 95% 0.6-0.91- in not supervised and ICC 0.81 CI
      95% 0.63-0.92 in supervised group). However, supervision helped trainees to
      acquire skills more rapidly and to perform more accurate measurements (ICC 0.77
      (95% CI 0.39-0.94) to ICC 0.91 (95% CI 0.77-0.98) and ICC 0.66 (95% CI 0.11-0.91)
      to ICC 0.84 (95% CI 0.58-0.96), respectively. CONCLUSION: TCCD of the MCA in
      volunteers is an easy to learn tool with a favorable learning curve. A short-term
      learning program including initial supervised measurements yields reliable
      results in the hands of inexperienced operators.

PMID- 25057934
TI  - Multimodal neurological approach can lead the treatment in postcardiac arrest
      persistent refractory status epilepticus.
AB  - Refractory status epilepticus (RSE) is a common challenge in the setting of post
      resuscitation care. We describe how multimodal neurological approach can lead
      treatment and improve the prognosis. We report on three survivors of cardiac
      arrest (CA) who had good neurological outcomes after mild hypothermia (TH),
      despite exhibiting persisting RSE requiring treatment with several antiepileptic
      (AED) and anesthetic drugs, including barbiturate-induced coma. No evidence-based
      data exist to guide management of RSE in the setting of anoxic brain injury. Our
      cases emphasize the need for continuous active treatment led by a multimodal
      approach in order to improve neurological outcome. 

PMID- 25057935
TI  - Postoperative acute kidney injury.
AB  - Acute kidney injury (AKI) represents 18-47% of all causes of hospital-acquired
      AKI and it is associated with a high incidence of morbidity and mortality
      especially in patients requiring dialysis. Only recently, with the application of
      new AKI classifications and guidelines (RIFLE, AKIN and KDIGO), a more accurate
      evaluation of the real incidence of kidney dysfunction in patients undergoing
      surgery has been detailed. In patients undergoing non-cardiac, non-vascular and
      non-thoracic surgery several independent preoperative and intraoperative
      predictors of AKI have been identified. Nonetheless, no measure for AKI
      prevention reached a high level of recommendation, although hemodynamic
      monitoring and goal-directed fluid management may limit perioperative AKI.
      Cardiac surgery-related AKI and cardiopulmonary bypass-related AKI have been
      extensively evaluated and several preventive and treatment strategies have been
      developed. Open and endovascular surgery-related AKI have been compared and
      hydration is currently the only preventive strategy with a substantial level of
      efficacy. In addition, AKI in thoracic surgery, overlooked in the past, has been
      evaluated, showing that it frequently complicates postoperative course of
      patients undergoing elective lung cancer resection. Multi-hit mechanisms
      (ischemia, inflammation, toxins) co-act on patients' predisposition
      (susceptibility). A multi-step approach is probably necessary to limit the
      incidence and the severity of postsurgery AKI patients, such as careful risk
      stratification, adoption of preventive measures and goal directed intraoperative
      algorithms. The present review will summarize the current literature about the
      epidemiology of postoperative AKI focusing on patient-related and technical
      related risk factors, outcome and prevention strategies in different groups of
      surgeries. 

PMID- 25057936
TI  - Interferon gamma in association with immunosuppressive drugs withdrawal and
      antifungal combination as a rescue therapy for cerebral invasive Aspergillosis in
      a liver transplant recipient.

PMID- 25057937
TI  - Old mineshaft, new canary: can circulating osteopontin concentrations predict
      septic shock?

PMID- 25057938
TI  - Association of socioeconomic status with overall and cause specific mortality in
      the Republic of Seychelles: results from a cohort study in the African region.
AB  - BACKGROUND: Low socioeconomic status (SES) is consistently associated with higher
      mortality in high income countries. Only few studies have assessed this
      association in low and middle income countries, mainly because of sparse reliable
      mortality data. This study explores SES differences in overall and cause-specific
      mortality in the Seychelles, a rapidly developing small island state in the
      African region. METHODS: All deaths have been medically certified over more than
      two decades. SES and other lifestyle-related risk factors were assessed in a
      total of 3246 participants from three independent population-based surveys
      conducted in 1989, 1994 and 2004. Vital status was ascertained using linkage with
      vital statistics. Occupational position was the indicator of SES used in this
      study and was assessed with the same questions in the three surveys. RESULTS:
      During a mean follow-up of 15.0 years (range 0-23 years), 523 participants died
      (overall mortality rate 10.8 per 1000 person-years). The main causes of death
      were cardiovascular disease (CVD) (219 deaths) and cancer (142 deaths).
      Participants in the low SES group had a higher mortality risk for overall (HR =
      1.80; 95% CI: 1.24-2.62), CVD (HR = 1.95; 1.04-3.65) and non-cancer/non-CVD (HR =
      2.14; 1.10-4.16) mortality compared to participants in the high SES group. Cancer
      mortality also tended to be patterned by SES (HR = 1.44; 0.76-2.75). Major
      lifestyle-related risk factors (smoking, heavy drinking, obesity, diabetes,
      hypertension, hypercholesterolemia) explained a small proportion of the
      associations between low SES and all-cause, CVD, and non-cancer/non-CVD
      mortality. CONCLUSIONS: In this population-based study assessing social
      inequalities in mortality in a country of the African region, low SES (as
      measured by occupational position) was strongly associated with overall, CVD and
      non-cancer/non-CVD mortality. Our findings support the view that the burden of
      non-communicable diseases may disproportionally affect people with low SES in low
      and middle income countries.

PMID- 25057939
TI  - Bcl-2-like protein 11 deletion polymorphism predicts survival in advanced non
      small-cell lung cancer.
AB  - INTRODUCTION: Germline Bcl-2-like protein 11 (BIM) deletion polymorphism in Asian
      is a poor predictive factor for treatment outcomes to tyrosine kinase inhibitors
      (TKIs) in malignancies. We explored the impact of BIM deletion polymorphism on
      treatment outcome of advanced non-small-cell lung cancer (NSCLC). METHODS: We
      prospectively collected tissue samples, blood, and clinical data from two cohorts
      of advanced NSCLC patients. BIM deletion polymorphism was correlated with overall
      survival (OS) and progression-free survival (PFS) to epidermal growth factor
      receptor (EGFR) TKIs and chemotherapy treatment. RESULTS: BIM deletion
      polymorphism was detected in blood of 16.2% (33 of 204) patients. The PFS to
      first-line EGFR-TKIs in 153 patients were 8.6 and 4.6 months for patients with
      wild-type BIM and BIM deletion polymorphism, respectively (p = 0.004). Among 120
      patients who received chemotherapies, the PFS to chemotherapies were 5.6 and 3.5
      months for patients with wild-type BIM and BIM deletion polymorphism,
      respectively (p = 0.050). The OS of all 204 patients was 24.8 and 16.8 months for
      patients with wild-type BIM and BIM deletion polymorphism, respectively (p =
      0.005). Multivariate analyses suggested that BIM deletion polymorphism was an
      independent predictor for shorter PFS to EGFR-TKIs (hazard ratio [HR] 2.15, p =
      0.002), PFS to chemotherapy (HR 2.40, p = 0.016), and OS (HR 1.65, p = 0.039).
      CONCLUSIONS: BIM deletion polymorphism predicts shorter PFS to EGFR-TKIs and OS
      in advanced NSCLC.

PMID- 25057940
TI  - V843I, a lung cancer predisposing EGFR mutation, is responsible for resistance to
      EGFR tyrosine kinase inhibitors.
AB  - INTRODUCTION: We previously demonstrated that a family predisposed to lung cancer
      harbored a V843I substitution in the epidermal growth factor receptor (EGFR)
      protein. We report here the further characterization of this mutant EGFR protein
      in the context of tumorigenicity and resistance to tyrosine kinase inhibitors
      (TKIs) of EGFR activity. METHODS: Phosphorylation of EGFR and downstream
      signaling proteins of lung adenocarcinoma cell lines with EGFR mutations was
      assayed by flow cytometry. Susceptibility to TKIs of these cell lines, with or
      without suppression of mutant EGFR expression by small inhibitory RNA (siRNA),
      was investigated using a cellular viability assay. Furthermore, protein modeling
      was used to predict TKI binding to EGFR protein carrying the V843I mutation.
      RESULTS: Phosphorylation of EGFR and downstream signaling proteins was elevated
      upon transfection with an EGFR gene with the V843I. Although the cell line with
      V843I + L858R demonstrated resistance to EGFR-TKIs, the cells became susceptible
      to TKIs upon incubation with siRNA specific for the V843I allele. The structural
      analysis suggested that TKI binding to EGFR would be sterically hindered by
      Arg841 in the double-mutant (V843I + L858R) EGFR. CONCLUSIONS: The V843I mutation
      contributes to tumorigenesis by promoting phosphorylation of EGFR and its
      downstream signaling proteins. This mutation also appears to provide resistance
      to EGFR-TKIs through structural modification of EGFR. These features are
      comparable with those in EGFR T790M mutation, suggesting that cases with germ
      line V843I or T790M mutations could be categorized as a class of familial lung
      cancer syndrome with resistance to EGFR-TKIs.

PMID- 25057941
TI  - Co-targeting c-Met and COX-2 leads to enhanced inhibition of lung tumorigenesis
      in a murine model with heightened airway HGF.
AB  - BACKGROUND: The hepatocyte growth factor (HGF)/c-Met pathway is often
      dysregulated in non-small-cell lung cancer (NSCLC). HGF activation of c-Met
      induces cyclooxygenase-2 (COX-2), resulting in downstream stimulation by
      prostaglandin E2 of additional pathways. Targeting both c-Met and COX-2 might
      lead to enhanced antitumor effects by blocking signaling upstream and downstream
      of c-Met. METHODS: Effects of crizotinib or celecoxib alone or in combination
      were tested in NSCLC cells in vitro and in mice transgenic for airway expression
      of human HGF. RESULTS: Proliferation and invasion of NSCLC cells treated with a
      combination of crizotinib and celecoxib were significantly lower compared with
      single treatments. Transgenic mice showed enhanced COX-2 expression localized to
      preneoplastic areas following exposure to the tobacco carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, which was not present without
      carcinogen exposure. This shows that COX-2 activity is present during lung tumor
      development in a high HGF environment. After 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone treatment, a significant decrease in the number of lung tumors per
      animal was observed after 13-week treatments of crizotinib, celecoxib, or the
      combination compared with placebo (p < 0.001). With combination treatment, the
      number of tumors was also significantly lower than single agent treatment (p <
      0.001). In the resulting lung tumors, P-c-Met, COX-2, prostaglandin E2, and P
      MAPK were significantly downmodulated by combination treatment compared with
      single treatment. Expression of the epithelial-mesenchymal transition markers E
      cadherin and snail was also modulated by combination treatment. CONCLUSIONS: In
      the presence of high HGF, dual inhibition of c-Met and COX-2 may enhance
      antitumor effects. This combination may have clinical potential in NSCLCs with
      high HGF/c-Met expression or epithelial-mesenchymal transition phenotype.

PMID- 25057943
TI  - Asymmetric global motion integration in drifting Gabor arrays.
AB  - We examined how ambiguous motion signals are integrated over space to support the
      unambiguous perception of global motion. The motion of a Gaussian windowed
      drifting sine grating (Gabor) is consistent with an infinite number of grating
      velocities. To extract the consistent global motion of multi-Gabor arrays, the
      visual system must integrate ambiguous motion signals from disparate regions of
      visual space. We found an interaction between spatial arrangement and global
      motion integration in this process. Linear arrays of variably oriented Gabor
      elements appeared to move more slowly, reflecting suboptimal integration, when
      the direction of global translation was orthogonal to the line as opposed to
      along it. Circular arrays of Gabor elements appeared to move more slowly when the
      global motion was an expansion or contraction rather than a rotation. However,
      there was no difference in perceived speed for densely packed annular arrays for
      these global motion pattern directions. We conclude that the region over which
      ambiguous motion is integrated is biased in the direction of global motion, and
      the concept of the association field, held to link like elements along a contour,
      needs to be extended to include global motion computation over disparate elements
      referencing the same global motion.

PMID- 25057942
TI  - Application of detergents or high hydrostatic pressure as decellularization
      processes in uterine tissues and their subsequent effects on in vivo uterine
      regeneration in murine models.
AB  - Infertility caused by ovarian or tubal problems can be treated using In Vitro
      Fertilization and Embryo Transfer (IVF-ET); however, this is not possible for
      women with uterine loss and malformations that require uterine reconstruction for
      the treatment of their infertility. In this study, we are the first to report the
      usefulness of decellularized matrices as a scaffold for uterine reconstruction.
      Uterine tissues were extracted from Sprague Dawley (SD) rats and decellularized
      using either sodium dodecyl sulfate (SDS) or high hydrostatic pressure (HHP) at
      optimized conditions. Histological staining and quantitative analysis showed that
      both SDS and HHP methods effectively removed cells from the tissues with,
      specifically, a significant reduction of DNA contents for HHP constructs. HHP
      constructs highly retained the collagen content, the main component of
      extracellular matrices in uterine tissue, compared to SDS constructs and had
      similar content levels of collagen to the native tissue. The mechanical strength
      of the HHP constructs was similar to that of the native tissue, while that of the
      SDS constructs was significantly elevated. Transmission electron microscopy (TEM)
      revealed no apparent denaturation of collagen fibers in the HHP constructs
      compared to the SDS constructs. Transplantation of the decellularized tissues
      into rat uteri revealed the successful regeneration of the uterine tissues with a
      3-layer structure 30 days after the transplantation. Moreover, a lot of
      epithelial gland tissue and Ki67 positive cells were detected.
      Immunohistochemical analyses showed that the regenerated tissues have a normal
      response to ovarian hormone for pregnancy. The subsequent pregnancy test after 30
      days transplantation revealed successful pregnancy for both the SDS and HHP
      groups. These findings indicate that the decellularized matrix from the uterine
      tissue can be a potential scaffold for uterine regeneration. 

PMID- 25057944
TI  - Measuring response saturation in human MT and MST as a function of motion
      density.
AB  - The human brain areas MT and MST have been studied in great detail using fMRI
      with regards to their motion processing properties; however, to what extent this
      corresponds with single cell recordings remains to be fully described. Average
      response over human MT+ has been shown to increase linearly with motion
      coherence, similar to single cell responses. In response to motion density some
      single cell data however suggest a rapid saturation. We ask how the combination
      of these responses is reflected in the population response. We measured the blood
      oxygen level dependent (BOLD) response function of MT and MST using a motion
      density signal, comparing with area V1. We used spatially fixed apertures
      containing motion stimuli to manipulate the area covered by motion. We found that
      MT and MST responded above baseline to a very minimal amount of motion and showed
      a rather flat response to motion density, indicative of saturation. We discuss
      how this may be related to the size of the receptive fields and inhibitory
      interactions, although necessarily residual attention effects also need to be
      considered. We then compared different types of motion and found no difference
      between coherent and random motion at any motion density, suggesting that when
      combining response over several motion stimuli covering the visual field, a
      linear relationship of MT and MST population response as a function of motion
      coherence might not hold. 

PMID- 25057945
TI  - Crossing the line: estimations of line length in the Oppel-Kundt illusion.
AB  - In the Oppel-Kundt illusion, one of the oldest and least understood geometrical
      visual illusions, a line subdivided by a series of short orthogonal ticks appears
      longer than an identical line without these. Paradoxically, bisecting a long line
      with a single tick leads to perceived shortening of the line. We have
      systematically investigated the effects of adding 1 to 12 ticks on perceived line
      length and results suggest that at least three mechanisms must be at work: (a)
      bisection, which reduces perceived length; (b) a filled extent effect, which is
      also apparent in the von Helmholtz illusion, though no satisfactory explanation
      for it exists; and (c) a local contour repulsion effect of the penultimate tick
      upon the perceived position of the end tick, but this effect, though significant,
      is too small to explain the Oppel-Kundt illusion in its entirety. 

PMID- 25057948
TI  - Primary biliary cirrhosis. Foreword.

PMID- 25057947
TI  - Manganese disturbs metal and protein homeostasis in Caenorhabditis elegans.
AB  - Parkinson's disease (PD) is a debilitating motor and cognitive neurodegenerative
      disorder for which there is no cure. While aging is the major risk factor for
      developing PD, clear environmental risks have also been identified. Environmental
      exposure to the manganese (Mn) metal is a prominent risk factor for developing PD
      and occupational exposure to high levels of Mn can cause a syndrome known as
      manganism, which has symptoms that closely resemble PD. In this study, we
      developed a model of manganism in the environmentally tractable nematode,
      Caenorhabditis elegans. We find that, in addition to previously described modes
      of Mn toxicity, which primarily include mitochondrial dysfunction and oxidative
      stress, Mn exposure also significantly antagonizes protein homeostasis, another
      key pathological feature associated with PD and many age-related
      neurodegenerative diseases. Mn treatment activates the ER unfolded protein
      response, severely exacerbates toxicity in a disease model of protein misfolding,
      and alters aggregate solubility. Further, aged animals, which have previously
      been shown to exhibit decreased protein homeostasis, are particularly susceptible
      to Mn toxicity when compared to young animals, indicating that the aging process
      sensitizes animals to metal toxicity. Mn exposure also significantly alters iron
      (Fe) and calcium (Ca) homeostasis, which is important for mitochondrial and ER
      health and which may further compound toxicity. These findings indicate that
      modeling manganism in C. elegans can provide a useful platform for identifying
      therapeutic interventions for ER stress, proteotoxicity, and age-dependent
      susceptibilities, key pathological features of PD and other related
      neurodegenerative diseases. 

PMID- 25057949
TI  - Genetics and epigenetics of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) has been considered a multifactorial autoimmune
      disease presumably arising from a combination of environmental and genetic
      factors, with genetic inheritance mostly suggested by familial occurrence and
      high concordance rate among monozygotic twins. In the last decade, genome-wide
      association studies, new data on sex chromosome defects and instabilities, and
      initial evidence on the role of epigenetic abnormalities have strengthened the
      crucial importance of genetic and epigenetic factors in determining the
      susceptibility of PBC. High-throughput genetic studies in particular have
      revolutionized the search for genetic influences on PBC and have the potential to
      be translated into clinical and therapeutic applications, although more
      biological knowledge on candidate genes is now needed. In this review, these
      recent discoveries will be critically summarized with particular focus on the
      possible steps that may transfer genetic and epigenetic knowledge to direct
      health benefits in patients with PBC. 

PMID- 25057952
TI  - Animal models of primary biliary cirrhosis.
AB  - Within the last decade, several mouse models that manifest characteristic
      features of primary biliary cirrhosis (PBC) with antimitochondrial antibodies
      (AMAs) and immune-mediated biliary duct pathology have been reported. Here, the
      authors discuss the current findings on two spontaneous (nonobese diabetic
      autoimmune biliary disease [NOD.ABD] and dominant negative transforming growth
      factor-beta receptor II [dnTGFbetaRII]) and two induced (chemical xenobiotics and
      microbial immunization) models of PBC. These models exhibit the serological,
      immunological, and histopathological features of human PBC. From these animal
      models, it is evident that the etiology of PBC is multifactorial and requires
      both specific genetic predispositions and environmental insults (either
      xenobiotic chemicals or microbial), which lead to the breaking of tolerance and
      eventually liver pathology. Human PBC is likely orchestrated by multiple factors
      and hence no single model can fully mimic the immunopathophysiology of human PBC.
      Nevertheless, knowledge gained from these models has greatly advanced our
      understanding of the major immunological pathways as well as the etiology of PBC.

PMID- 25057950
TI  - Environmental factors in primary biliary cirrhosis.
AB  - The etiology of the autoimmune liver disease primary biliary cirrhosis (PBC)
      remains largely unresolved, owing in large part to the complexity of interaction
      between environmental and genetic contributors underlying disease development.
      Observations of disease clustering, differences in geographical prevalence, and
      seasonality of diagnosis rates suggest the environmental component to PBC is
      strong, and epidemiological studies have consistently found cigarette smoking and
      history of urinary tract infection to be associated with PBC. Current evidence
      implicates molecular mimicry as a primary mechanism driving loss of tolerance and
      subsequent autoimmunity in PBC, yet other environmentally influenced disease
      processes are likely to be involved in pathogenesis. In this review, the authors
      provide an overview of current findings and touch on potential mechanisms behind
      the environmental component of PBC. 

PMID- 25057953
TI  - Breach of tolerance: primary biliary cirrhosis.
AB  - In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active
      disease involves a disruption in several layers of control, including central
      tolerance, peripheral anergy, a "liver tolerance effect," and the action of T
      regulatory cells and their related cytokines. Each of these control mechanisms
      plays a role in preventing an immune response against self, but all of them act
      in concert to generate effective protection against autoimmunity without
      compromising the ability of the host immune system to mount an effective response
      to pathogens. At the same time, genetic susceptibility, environmental factors,
      including infection agents and xenobiotics, play important roles in breach of
      tolerance in the development of PBC. 

PMID- 25057954
TI  - The new epidemiology of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease.
      Susceptibility to PBC probably arises from a combination of genetic and
      environmental factors. The prevalence of PBC varies both on an international and
      a regional level. This can be explained, in part, by differences in clinical
      practice and case-finding activity. It is likely, however, that substantive
      geographical differences exist both in terms of genetic susceptibility and
      environmental factors that potentially trigger the disease in genetically
      susceptible individuals. The study of the epidemiology of PBC has strongly
      supported the concept of an environmental triggering factor, but as yet no
      specific agent has been identified. Ongoing work to discover the environmental
      agent, as well as the mechanism that causes the disease will answer key questions
      as to the epidemiology of this complex autoimmune disease as well as providing
      useful information for other autoimmune conditions. 

PMID- 25057951
TI  - Role of cholangiocytes in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by
      selective destruction of intrahepatic cholangiocytes. Mechanisms underlying the
      development and progression of the disease are still controversial and largely
      undefined. Evidence suggests that PBC results from an articulated immunologic
      response against an immunodominant mitochondrial autoantigen, the E2 component of
      the pyruvate dehydrogenase complex (PDC-E2); characteristics of the disease are
      also the presence of disease-specific antimitochondrial autoantibodies (AMAs) and
      autoreactive CD4 and CD8 T cells. Recent evidence suggests that cholangiocytes
      show specific immunobiological features that are responsible for the selective
      targeting of those cells by the immune system. The immune reaction in PBC
      selectively targets small sized, intrahepatic bile ducts; although a specific
      reason for that has not been defined yet, it has been established that the
      biliary epithelium displays a unique heterogeneity, for which the physiological
      and pathophysiological features of small and large cholangiocytes significantly
      differ. In this review article, the authors provide a critical overview of the
      current evidence on the role of cholangiocytes in the immune-mediated destruction
      of the biliary tree that characterizes PBC. 

PMID- 25057955
TI  - The natural history of primary biliary cirrhosis.
AB  - Our understanding of the natural history of primary biliary cirrhosis (PBC) has
      been evolving especially following the introduction of ursodeoxycholic acid
      (UDCA). A clearer understanding of disease pathophysiology and earlier diagnosis
      with increased prevalence of the disease worldwide has led to increased interest
      and improved outcomes in patients with PBC. In this article, the authors touch
      briefly on features of the disease and describe the natural history of PBC prior
      to and after the introduction of UDCA. 

PMID- 25057956
TI  - Clinical significance of autoantibodies in primary biliary cirrhosis.
AB  - Antimitochondrial, anti-gp210, anti-sp100, and anticentromere antibodies are
      specifically detected in primary biliary cirrhosis (PBC). In clinical practice,
      they are useful for the diagnosis of PBC or for evaluating disease severity,
      clinical phenotype, and long-term outcome. In the typical or classical form of
      PBC which shows slow progressive loss of small bile ducts with a parallel
      increase in liver fibrosis, anti-gp210 antibodies are a strong risk factor for
      progression to jaundice and hepatic failure, whereas the presence of
      anticentromere antibodies is a risk factor for progression to cirrhosis and
      portal hypertension. Of note, the autoimmune repertoire, which is established
      during the early stage of the disease process, can influence the clinical
      phenotype and the long-term prognosis of PBC. Because the natural course of PBC
      is being altered by treatment with ursodeoxycholic acid, the clinical
      significance of these PBC-specific autoantibodies awaits re-evaluation in various
      ethnicities. 

PMID- 25057957
TI  - Old and novel therapies for primary biliary cirrhosis.
AB  - Despite the presumed immunological pathogenesis of primary biliary cirrhosis, no
      clear or even harmful consequences resulted from some specific treatments
      addressed to modify the immunological condition. However, ursodeoxycholic acid
      (UDCA; 13-16 mg/kg/d) has clear favorable effects not only by improving
      biochemical cholestasis, but also by delaying the histological progression. Long 
      term treatment with UDCA is associated with excellent survival, free of
      transplantation in cases showing biochemical response at one year. In the
      remaining patients, data on the effect of fibrates, budesonide, or obeticholic
      acid are encouraging. Pruritus is usually managed using resins; further steps are
      needed in resistant cases with the use of rifampicin, naltrexone, sertraline, or
      invasive procedures such as albumin dialysis. Osteoporosis, which is highly
      prevalent in patients with deep and prolonged cholestasis, improves with
      bisphosphonates; current data indicate that both weekly alendronate and monthly
      ibandronate increase bone mass in patients with osteoporosis. Nutritional and fat
      vitamin supplementation is also mandatory in patients with severe cholestasis. 

PMID- 25057958
TI  - Primary biliary cirrhosis: overlaps with other autoimmune disorders.
AB  - In this article, the authors use the term "overlaps" to refer to the coexistence
      of primary biliary cirrhosis (PBC) with another autoimmune condition that
      involves the liver or extrahepatic organs. Diagnosing PBC-autoimmune hepatitis
      (PBC-AIH) overlap syndrome remains a challenge, especially because there is still
      no consensus on the most appropriate diagnostic criteria. The prevalence of this
      condition varies considerably among series of PBC patients, and its treatment
      demands a combination of ursodeoxycholic acid and immunosuppressive drugs.
      Overlap syndrome between PBC and primary sclerosing cholangitis is described in
      exceptional cases. About one in three PBC patients have a concomitant
      extrahepatic autoimmune disease, which may include rheumatological,
      endocrinological, gastrointestinal, pulmonary, or dermatological conditions.
      Overlaps raise several questions, about whether they share much the same genetic
      susceptibility, as is generally assumed. The pathogenesis of these conditions
      includes the production of both innate and adaptive immune responses targeting
      cholangiocytes as well as different extrahepatic tissues. In this sense, overlaps
      in PBC represent a continuous spectrum of autoimmunity involving liver and
      extrahepatic tissues. 

PMID- 25057959
TI  - Gastrointestinal system complications in percutaneous nephrolithotomy: a
      systematic review.
AB  - PURPOSE: To evaluate gastrointestinal tract complications of percutaneous
      nephrolithotomy (PCNL), to determine risk factors, and to develop strategies for
      diagnosis and treatment. MATERIAL AND METHODS: A literature review was conducted
      for the studies published in the English language in the databases of PubMed and
      Scopus between July 1985 and June 2013. The key words for digital literature
      search were limited to the following: "percutaneous nephrolithotomy
      complications, ([splenic injury, liver injury, gallbladder injury and biliary
      peritonitis, colonic injury] during/after [percutaneous nephrolithotomy]),
      complication, Clavien, Clavien-Dindo classification, management, review, PNL,
      PCNL." RESULTS: A total of 16 articles on splenic injury were reviewed. There was
      no consensus in the literature regarding the management of splenic injuries. A
      conservative approach with new treatment modalities is the most widely accepted
      method in the literature. A total of seven articles on gallbladder injury were
      reviewed. All gallbladder injuries resulted in cholecystectomy. The time of
      diagnosis is the most significant parameter determining choice between
      laparoscopy and laparotomy. A total of seven articles on liver injury were
      reviewed. The liver injury generally provides the best response to a conservative
      approach among other solid organ injuries. A total of 11 articles on bowel injury
      were reviewed. Bowel injury mostly results in exploratory laparotomy. Unlike
      colon injuries, bowel injuries are more complex to manage with conservative
      measures because of the challenges in diagnosis and the fact that the injury is
      located in the intraperitoneal area. A total of 28 articles, which comprised a
      large case series with colon injuries, consisted of collaborative reviews and
      meta-analyses were reviewed. In total, 51 colon injuries (0.5%) were evaluated
      occurring in 13,424 patients in supine and prone PCNL series. Conservative
      approaches have proven to be effective in colon injuries in the absence of large
      perforations and intraperitoneal involvement. CONCLUSION: There is a downward
      trend in gastrointestinal complications from PCNL because of the technologic
      advances that guide the diagnosis and treatment. Paradoxically, the rate of
      complications is higher in complex kidney stones such as those in a horseshoe
      kidney and pelvic and malrotated kidney that represent anatomic challenges for
      intervention. The most important point is to determine the risk factors for
      preoperative planning of the procedure and to diagnose the complications for
      proper management early.

PMID- 25057960
TI  - Structured light scatteroscopy.
AB  - A new imaging approach, structured light scatteroscopy (SLS), is demonstrated,
      which offers rapid wide-field imaging of microscopic morphological variations in
      bulk tissue surfaces. Elastic scattering of light offers exquisite sensitivity to
      ultrastructural changes at multiple size scales ranging from nanometers to
      millimeters, but in bulk tissues the confounding effects of molecular absorption
      and strong multiple scattering of light often lead to a dramatic reduction in
      scatter contrast and specificity. It is demonstrated that the SLS using
      structured high spatial frequency illumination and detection to probe the tissue
      achieves direct, absorption-independent, high-resolution maps of the scattering
      response. The scattering response is observed to be dependent on both the
      wavelength and spatial frequency of choice, indicating a potential for multiscale
      probing of ultrastructural changes in superficial tissue layers. This methodology
      can be easily applied in most wide-field imaging systems.

PMID- 25057961
TI  - Cost-efficient laser-diode-induced optical-resolution photoacoustic microscopy
      for two-dimensional/three-dimensional biomedical imaging.
AB  - Solid-state laser systems, such as traditional Nd:YAG-based lasers, are commonly
      used for noninvasive biomedical photoacoustics with nanosecond pulse duration and
      millijoule pulse energy. However, such lasers are both bulky and expensive for
      use as a handy tool for clinical applications. As an alternative, a semiconductor
      light source has the advantages of being compact, inexpensive, and robust. In
      addition, the main drawback of low peak output power may make it exactly suitable
      for the imaging modalities, which require relatively low pulse energies, such as
      acoustic- and optical-resolution photoacoustic microscopy (AR/OR-PAM). We propose
      a cost-efficient OR-PAM for two-dimensional/three-dimensional (2-D/3-D)
      biological imaging based on a pulsed near-infrared laser diode. By raster
      scanning, typical 2-D photoacoustic images were obtained at different scales, and
      3-D surface renderings were clearly reconstructed with a marching cubes
      algorithm. This initial study would promote the production of portable OR-PAM
      technology for clinical and biomedical applications.

PMID- 25057962
TI  - Engineering light-emitting diode surgical light for near-infrared fluorescence
      image-guided surgical systems.
AB  - The near-infrared (NIR) fluorescence signal in the 700 to 900 nm from molecular
      probes used in fluorescence image-guided surgery (FIGS) is usually weak compared
      to the NIR component from white light-emitting diode surgical light, which is
      typically switched off during FIGS to enhance the molecular fluorescence contrast
      of the image. We propose a simple solution to this critical issue in FIGS by
      removing NIR light from surgical light with a low cost commercial 3M cool mirror
      film 330.

PMID- 25057963
TI  - Simulation study of melanoma detection in human skin tissues by laser-generated
      surface acoustic waves.
AB  - Air pollution has been correlated to an increasing number of cases of human skin
      diseases in recent years. However, the investigation of human skin tissues has
      received only limited attention, to the point that there are not yet satisfactory
      modern detection technologies to accurately, noninvasively, and rapidly diagnose
      human skin at epidermis and dermis levels. In order to detect and analyze severe
      skin diseases such as melanoma, a finite element method (FEM) simulation study of
      the application of the laser-generated surface acoustic wave (LSAW) technique is
      developed. A three-layer human skin model is built, where LSAW's are generated
      and propagated, and their effects in the skin medium with melanoma are analyzed.
      Frequency domain analysis is used as a main tool to investigate such issues as
      minimum detectable size of melanoma, filtering spectra from noise and from
      computational irregularities, as well as on how the FEM model meshing size and
      computational capabilities influence the accuracy of the results. Based on the
      aforementioned aspects, the analysis of the signals under the scrutiny of the
      phase velocity dispersion curve is verified to be a reliable, a sensitive, and a
      promising approach for detecting and characterizing melanoma in human skin.

PMID- 25057964
TI  - Arsenic induced myocardial toxicity in rats: alleviative effect of Trichosanthes
      dioica fruit.
AB  - The present study investigated the alleviative effect of aqueous extract of
      Trichosanthes dioica fruit (AQTD) against arsenic induced cardiotoxicity in
      Wistar albino rats. AQTD (50 and 100 mg/kg) was administered orally to rats for
      20 consecutive days before oral administration of sodium arsenite (10 mg/kg) for
      8 days. Then the body weights, heart weights, hematological profile, serum
      biochemical profile; myocardial antioxidative parameters viz. lipid peroxidation,
      reduced and oxidized glutathione, glutathione-S-transferase, glutathione
      peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD),
      catalase (CAT), and DNA fragmentation were evaluated. Pretreatment with AQTD
      markedly and significantly normalized body weights, heart weights, hematological
      profile, serum biochemical profile and significantly modulated all the myocardial
      antioxidative parameters and reduced DNA fragmentation in arsenic intoxicated
      rats. Therefore, T. dioica fruit possessed remarkable alleviative effects against
      arsenic induced myocardial toxicity in Wistar albino rats mediated by
      amelioration of arsenic induced myocardial oxidative stress by several
      mechanisms.

PMID- 25057965
TI  - Life Expectancy after Inpatient Rehabilitation for Traumatic Brain Injury in the
      United States.
AB  - This study characterized life expectancy after traumatic brain injury (TBI). The
      TBI Model Systems (TBIMS) National Database (NDB) was weighted to represent those
      >=16 years of age completing inpatient rehabilitation for TBI in the United
      States (US) between 2001 and 2010. Analyses included Standardized Mortality
      Ratios (SMRs), Cox regression, and life expectancy. The US mortality rates by
      age, sex, race, and cause of death for 2005 and 2010 were used for comparison
      purposes. Results indicated that a total of 1325 deaths occurred in the weighted
      cohort of 6913 individuals. Individuals with TBI were 2.23 times more likely to
      die than individuals of comparable age, sex, and race in the general population,
      with a reduced average life expectancy of 9 years. Independent risk factors for
      death were: older age, male gender, less-than-high school education, previously
      married at injury, not employed at injury, more recent year of injury, fall
      related TBI, not discharged home after rehabilitation, less functional
      independence, and greater disability. Individuals with TBI were at greatest risk
      of death from seizures; accidental poisonings; sepsis; aspiration pneumonia;
      respiratory, mental/behavioral, or nervous system conditions; and other external
      causes of injury and poisoning, compared with individuals in the general
      population of similar age, gender, and race. This study confirms prior life
      expectancy study findings, and provides evidence that the TBIMS NDB is
      representative of the larger population of adults receiving inpatient
      rehabilitation for TBI in the US. There is an increased risk of death for
      individuals with TBI requiring inpatient rehabilitation. 

PMID- 25057967
TI  - In vitro sensing of Cu(+) through a green fluorescence rise of pyranine.
AB  - Pyranine as a new class of fluorescent chemosensor for the Cu(+) ion is reported.
      The probe is capable of discriminating ranges of cations from the Cu(+) ion, even
      in competing environment. The dye displayed a rapid fluorescence response (t1/2 =
      1.66 min) towards the Cu(+) ion, and the micromolar detection limit enabled the
      detection of the ion in environmental samples. The observed stoichiometry of
      complexation between pyranine and Cu(+) was 2 : 1. Interestingly, the sensing
      characteristic was specific to only neutral pH. A metal-to-ligand charge-transfer
      (MLCT)-based mechanism of sensing was proposed based on electron spin resonance
      (EPR), Raman spectroscopic and cyclic voltammetric studies. 

PMID- 25057966
TI  - Cytotoxic and pathogenic properties of Klebsiella oxytoca isolated from
      laboratory animals.
AB  - Klebsiella oxytoca is an opportunistic pathogen implicated in various clinical
      diseases in animals and humans. Studies suggest that in humans K. oxytoca exerts
      its pathogenicity in part through a cytotoxin. However, cytotoxin production in
      animal isolates of K. oxytoca and its pathogenic properties have not been
      characterized. Furthermore, neither the identity of the toxin nor a complete
      repertoire of genes involved in K. oxytoca pathogenesis have been fully
      elucidated. Here, we showed that several animal isolates of K. oxytoca, including
      the clinical isolates, produced secreted products in bacterial culture
      supernatant that display cytotoxicity on HEp-2 and HeLa cells, indicating the
      ability to produce cytotoxin. Cytotoxin production appears to be regulated by the
      environment, and soy based product was found to have a strong toxin induction
      property. The toxin was identified, by liquid chromatography-mass spectrometry
      and NMR spectroscopy, as low molecular weight heat labile benzodiazepine,
      tilivalline, previously shown to cause cytotoxicity in several cell lines,
      including mouse L1210 leukemic cells. Genome sequencing and analyses of a
      cytotoxin positive K. oxytoca strain isolated from an abscess of a mouse,
      identified genes previously shown to promote pathogenesis in other enteric
      bacterial pathogens including ecotin, several genes encoding for type IV and type
      VI secretion systems, and proteins that show sequence similarity to known
      bacterial toxins including cholera toxin. To our knowledge, these results
      demonstrate for the first time, that animal isolates of K. oxytoca, produces a
      cytotoxin, and that cytotoxin production is under strict environmental
      regulation. We also confirmed tilivalline as the cytotoxin present in animal K.
      oxytoca strains. These findings, along with the discovery of a repertoire of
      genes with virulence potential, provide important insights into the pathogenesis
      of K. oxytoca. As a novel diagnostic tool, tilivalline may serve as a biomarker
      for K oxytoca-induced cytotoxicity in humans and animals through detection in
      various samples from food to diseased samples using LC-MS/MS. Induction of K.
      oxytoca cytotoxin by consumption of soy may be in part involved in the
      pathogenesis of gastrointestinal disease. 

PMID- 25057968
TI  - Characterizing and predicting submovements during human three-dimensional arm
      reaches.
AB  - We have demonstrated that 3D target-oriented human arm reaches can be represented
      as linear combinations of discrete submovements, where the submovements are a set
      of minimum-jerk basis functions for the reaches. We have also demonstrated the
      ability of deterministic feed-forward Artificial Neural Networks (ANNs) to
      predict the parameters of the submovements. ANNs were trained using kinematic
      data obtained experimentally from five human participants making target-directed
      movements that were decomposed offline into minimum-jerk submovements using an
      optimization algorithm. Under cross-validation, the ANNs were able to accurately
      predict the parameters (initiation-time, amplitude, and duration) of the
      individual submovements. We also demonstrated that the ANNs can together form a
      closed-loop model of human reaching capable of predicting 3D trajectories with
      VAF >95.9% and RMSE <=4.32 cm relative to the actual recorded trajectories. This
      closed-loop model is a step towards a practical arm trajectory generator based on
      submovements, and should be useful for the development of future arm prosthetic
      devices that are controlled by brain computer interfaces or other user
      interfaces. 

PMID- 25057969
TI  - The theory of planned behavior as applied to preoperative smoking abstinence.
AB  - Abstinence from smoking on the morning of surgery may improve outcomes. This
      study examined the explicatory power of the Theory of Planned Behavior (TPB) to
      predict smoking behavior on the morning of surgery, testing the hypothesis that
      the constructs of attitude, subjective norm, and perceived behavioral control
      (PBC) will predict intent to abstain from smoking the morning of surgery, and
      that intent will predict behavior. TPB constructs were assessed in 169 pre
      surgical patients. Smoking behavior on the morning of surgery was assessed by
      self-report and CO monitoring. Correlations and structural equation modeling
      (SEM) were used to determine associations between measures and behavior. All TPB
      measures, including intent as predicted by the TPB, were correlated with both a
      lower rate of self-reported smoking on the morning of surgery and lower CO
      levels. The SEM showed a good fit to the data. In the SEM, attitude and PBC, but
      not subjective norm, were significantly associated with intent to abstain,
      explaining 46% of variance. The effect of PBC on CO levels was partially mediated
      by intent. The amount of variance in behavior explained by these TPB constructs
      was modest (10% for CO levels). Thus, attitude and perceived behavioral control
      explain a substantial portion of the intent to maintain preoperative abstinence
      on the morning of elective surgery, and intent and perceived behavioral control
      explain a more modest but significant amount of the variance in actual smoking
      behavior. TRIAL REGISTRATION: Clinical Trials.gov registration: NCT01014455.

PMID- 25057970
TI  - Hydrophobic effects on supported ionic liquid phase Pd nanoparticle hydrogenation
      catalysts.
AB  - Hybrid organosilicas prepared by sol-gel processes using 1-n-butyl-3-(3
      trimethoxysilylpropyl)-imidazolium cations associated with hydrophilic and
      hydrophobic anions can be easily decorated with well dispersed and similar size
      (1.8-2.1 nm) Pd nanoparticles (Pd-NPs) by simple sputtering-deposition. Higher Pd
      concentration at the surface compared to the deeper region is obtained in the
      supports with smaller pore diameter (containing hydrophobic ILs) than in supports
      with the largest pore diameter (containing hydrophilic ILs). The IL
      hydrophobicity plays a central role in the hydrogenation of dienes by controlling
      the diene access to NP surface active sites. 

PMID- 25057971
TI  - A promising light for an impossible disease: miRNAs in malignant gliomas.

PMID- 25057974
TI  - A selected review of abstracts from the 17th Annual Scientific Meeting of the
      Society for Neuro-Oncology.
AB  - The Annual Scientific Meeting of the Society for Neuro-Oncology (SNO) is the
      largest neuro-oncology annual meeting in the USA and provides an exciting venue
      for the presentation of new brain cancer clinical trials and research data
      primarily pertaining to gliomas. The SNO 2012 meeting, comprising of one
      education day, three days of presentation, 80 oral presentations and 400
      abstracts, provides a current overview of neuro-oncology including metastatic
      diseases of the CNS as well as primary brain tumors. This short article,
      highlights select abstracts presented at this meeting to provide a snapshot of a
      large and multifaceted meeting. 

PMID- 25057975
TI  - Comprehensive neuraxis imaging in leptomeningeal metastasis: a retrospective case
      series.
AB  - AIM: Quantify imaging abnormalities in a retrospective case series of patients
      with leptomeningeal metastasis (LM). METHODS: A total of 240 adult patients with
      LM (125 nonbrain solid tumor patients with positive cerebrospinal fluid [CSF]
      cytology; 40 nonbrain solid tumor patients with negative CSF cytology and
      positive MRI; and 50 lymphoma and 25 leukemia patients with positive CSF-flow
      cytometry) underwent brain and entire spine MRI and radioisotope CSF-flow studies
      prior to treatment. RESULTS: MRI was more often abnormal in solid tumors (40 CSF
      defined and 100% in MRI defined) compared with hematologic cancers (16-20%; p =
      0.03). Similarly, CSF-flow studies was more often abnormal in solid tumors (25
      28%) compared with hematologic cancers (10-20%; p = 0.04). MRI and flow-study
      abnormalities altered therapy in a third of solid tumors and 15% of hematologic
      cancers. CONCLUSION: Although imaging abnormalities are less often seen in
      hematologic cancers compared with solid tumor LM, imaging abnormalities
      frequently result in treatment alteration.

PMID- 25057976
TI  - Optic pathway gliomas: a review.
AB  - Optic pathway gliomas account for 3-5% of all pediatric CNS tumors and represent
      the most common intrinsic optic nerve tumors. These tumors occur preferentially
      during the first decade of life and are particularly frequent in children with
      neurofibromatosis type 1. Although optic pathway gliomas are low-grade tumors,
      their behavior can be aggressive, and their management is often challenging.
      Their management includes observation, surgery, chemotherapy and radiation. The
      role of each modality is discussed as well as current and future developments in
      treatment, in particular targeted therapies that are currently being
      investigated.

PMID- 25057977
TI  - Medical management of meningiomas.
AB  - The efficacy of surgery and radiation has been well validated in the treatment of
      meningiomas, with efficacy depending on tumor pathology, size, symptomatology and
      rate of progression. The role of medical therapy has the least amount of data but
      is being increasingly investigated for tumors that are inoperable or those tumors
      that recur and/or progress despite standard therapy. In this review, current data
      on the use of chemotherapeutic agents in the management of meningiomas will be
      reviewed, including cytotoxic, biologic, targeted molecular and hormonal agents.

PMID- 25057978
TI  - Relationship between cognitive function and prognosis in glioblastoma.
AB  - The association between increased signs and symptoms and poorer survival in
      glioblastoma is well recognized and confirmed in virtually every clinical trial
      and patient series. Measurement and consideration of performance status is,
      therefore, vital when counseling patients regarding their expected survival or
      evaluating the results of clinical trials. Unfortunately, measures of patient
      function in clinical trials have remained quite crude, in stark contrast to the
      rapid advances seen in the pathological characterization of brain tumors.
      Recently, clinical investigators have begun to examine the subcomponents of
      performance status in more detail, revealing that objective measures of cognition
      are significantly associated with patient survival in both newly diagnosed and
      recurrent glioblastoma. Furthermore, cognitive function does not appear to be a
      simple proxy for performance status but rather an independent predictor of
      survival, even within patient groups defined by currently available clinical
      prognostic systems. Therefore, objective measures of cognition must be evaluated
      for inclusion in future prognostic models and the simple addition of new tumor
      biomarkers to the current clinical prognostic models will likely prove
      insufficient. In order for the field of neuro-oncology to move forward in this
      regard, evaluation of cognition must become a routine part of future clinical
      trials, and the data must be recorded and analyzed with the same diligence as
      other trial end points.

PMID- 25057979
TI  - Postsurgical management strategies in patients with skull base chondrosarcomas.
AB  - Chondrosarcomas of the skull base are rare, slow-growing tumors that are often
      lethal and remain a management quandary. A systematic review was performed to
      understand postsurgical management options for patients with these tumors. The
      current standard of care includes surgical resection followed by either adjuvant
      radiation therapy and/or early radiosurgery. The role of chemotherapy has been
      limited, but remains under investigation. Overall survival and progression-free
      survival range between 70 and 100% at 5 years when multimodality approaches are
      used. Overall survival may be greater for patients who have a shorter interval
      (<6 months) between diagnosis and radiosurgery, an older age, and either a single
      or no prior resection. Progression-free survival may be increased for patients
      older than 40 years of age, who have not had prior radiation therapy, and for
      those with smaller tumors that do not compress the brainstem.

PMID- 25057981
TI  - Pulmonary disease in cystic fibrosis: assessment with chest CT at chest
      radiography dose levels.
AB  - PURPOSE: To investigate a computed tomographic (CT) protocol with iterative
      reconstruction at conventional radiography dose levels for the assessment of
      structural lung abnormalities in patients with cystic fibrosis ( CF cystic
      fibrosis ). MATERIALS AND METHODS: In this institutional review board-approved
      study, 38 patients with CF cystic fibrosis (age range, 6-58 years; 21 patients
      <18 years and 17 patients >18 years) underwent investigative CT (at minimal
      exposure settings combined with iterative reconstruction) as a replacement of
      yearly follow-up posteroanterior chest radiography. Verbal informed consent was
      obtained from all patients or their parents. CT images were randomized and rated
      independently by two radiologists with use of the Bhalla scoring system. In
      addition, mosaic perfusion was evaluated. As reference, the previous available
      conventional chest CT scan was used. Differences in Bhalla scores were assessed
      with the chi(2) test and intraclass correlation coefficients ( ICC intraclass
      correlation coefficient s). Radiation doses for CT and radiography were assessed
      for adults (>18 years) and children (<18 years) separately by using technical
      dose descriptors and estimated effective dose. Differences in dose were assessed
      with the Mann-Whitney U test. RESULTS: The median effective dose for the
      investigative protocol was 0.04 mSv (95% confidence interval [ CI confidence
      interval ]: 0.034 mSv, 0.10 mSv) for children and 0.05 mSv (95% CI confidence
      interval : 0.04 mSv, 0.08 mSv) for adults. These doses were much lower than those
      with conventional CT (median: 0.52 mSv [95% CI confidence interval : 0.31 mSv,
      3.90 mSv] for children and 1.12 mSv [95% CI confidence interval : 0.57 mSv, 3.15
      mSv] for adults) and of the same order of magnitude as those for conventional
      radiography (median: 0.012 mSv [95% CI confidence interval : 0.006 mSv, 0.022
      mSv] for children and 0.012 mSv [95% CI confidence interval : 0.005 mSv, 0.031
      mSv] for adults). All images were rated at least as diagnostically acceptable.
      Very good agreement was found in overall Bhalla score ( ICC intraclass
      correlation coefficient , 0.96) with regard to the severity of bronchiectasis (
      ICC intraclass correlation coefficient , 0.87) and sacculations and abscesses (
      ICC intraclass correlation coefficient , 0.84). Interobserver agreement was
      excellent ( ICC intraclass correlation coefficient , 0.86-1). CONCLUSION: For
      patients with CF cystic fibrosis , a dedicated chest CT protocol can replace the
      two yearly follow-up chest radiographic examinations without major dose penalty
      and with similar diagnostic quality compared with conventional CT.

PMID- 25057982
TI  - 8.2% of the Human genome is constrained: variation in rates of turnover across
      functional element classes in the human lineage.
AB  - Ten years on from the finishing of the human reference genome sequence, it
      remains unclear what fraction of the human genome confers function, where this
      sequence resides, and how much is shared with other mammalian species. When
      addressing these questions, functional sequence has often been equated with pan
      mammalian conserved sequence. However, functional elements that are short-lived,
      including those contributing to species-specific biology, will not leave a
      footprint of long-lasting negative selection. Here, we address these issues by
      identifying and characterising sequence that has been constrained with respect to
      insertions and deletions for pairs of eutherian genomes over a range of
      divergences. Within noncoding sequence, we find increasing amounts of mutually
      constrained sequence as species pairs become more closely related, indicating
      that noncoding constrained sequence turns over rapidly. We estimate that half of
      present-day noncoding constrained sequence has been gained or lost in
      approximately the last 130 million years (half-life in units of divergence time,
      d1/2 = 0.25-0.31). While enriched with ENCODE biochemical annotations, much of
      the short-lived constrained sequences we identify are not detected by models
      optimized for wider pan-mammalian conservation. Constrained DNase 1
      hypersensitivity sites, promoters and untranslated regions have been more
      evolutionarily stable than long noncoding RNA loci which have turned over
      especially rapidly. By contrast, protein coding sequence has been highly stable,
      with an estimated half-life of over a billion years (d1/2 = 2.1-5.0). From
      extrapolations we estimate that 8.2% (7.1-9.2%) of the human genome is presently
      subject to negative selection and thus is likely to be functional, while only
      2.2% has maintained constraint in both human and mouse since these species
      diverged. These results reveal that the evolutionary history of the human genome
      has been highly dynamic, particularly for its noncoding yet biologically
      functional fraction. 

PMID- 25057983
TI  - MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting
      miR-361.
AB  - Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but
      whether lncRNAs operate in the processing of miRNA primary transcript is unclear.
      Also, whether lncRNAs are involved in the regulation of the mitochondrial network
      remains to be elucidated. Here, we report that a long noncoding RNA, named
      mitochondrial dynamic related lncRNA (MDRL), affects the processing of miR-484
      primary transcript in nucleus and regulates the mitochondrial network by
      targeting miR-361 and miR-484. The results showed that miR-361 that predominantly
      located in nucleus can directly bind to primary transcript of miR-484 (pri-miR
      484) and prevent its processing by Drosha into pre-miR-484. miR-361 is able to
      regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In
      exploring the underlying molecular mechanism by which miR-361 is regulated, we
      identified MDRL and demonstrated that it could directly bind to miR-361 and
      downregulate its expression levels, which promotes the processing of pri-miR-484.
      MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361,
      which in turn relieves inhibition of miR-484 processing by miR-361. Our present
      study reveals a novel regulating model of mitochondrial fission program which is
      composed of MDRL, miR-361 and miR-484. Our work not only expands the function of
      the lncRNA pathway in gene regulation but also establishes a new mechanism for
      controlling miRNA expression. 

PMID- 25057984
TI  - Fusion of a short peptide that binds immunoglobulin G to a recombinant protein
      substantially increases its plasma half-life in mice.
AB  - We explore a strategy to substantially increase the half-life of recombinant
      proteins by genetic fusion to FcIII, a 13-mer IgG-Fc domain binding peptide
      (IgGBP) originally identified by DeLano and co-workers at Genentech [DeLano WL,
      et al. (2000) Science 287:1279-1283]. IgGBP fusion increases the in vivo half
      life of proteins by enabling the fusion protein to bind serum IgG, a concept
      originally introduced by DeLano and co-workers in a patent but that to the best
      of our knowledge has never been pursued in the scientific literature. To further
      investigate the in vitro and in vivo properties of IgGBP fusion proteins, we
      fused FcIII to the C-terminus of a model fluorescent protein, monomeric Katushka
      (mKate). mKate-IgGBP fusions are easily expressed in Escherichia coli and bind
      specifically to human IgG with an affinity of ~ 40 nM and ~ 20 nM at pH 7.4 and
      pH 6, respectively, but not to mouse or rat IgG isotypes. mKate-IgGBP binds the
      Fc-domain of hIgG1 at a site overlapping the human neonatal Fc receptor (hFcRn)
      and as a consequence inhibits the binding of hIgG1 to hFcRn in vitro. High
      affinity binding to human IgG also endows mKate-IgGBP with a long circulation
      half-life of ~ 8 hr in mice, a 75-fold increase compared to unmodified mKate.
      Thus, IgGBP fusion significantly reduces protein clearance by piggybacking on
      serum IgG without substantially increasing protein molecular weight due to the
      small size of the IgGBP. These attractive features could result in protein
      therapies with reduced dose frequency and improved patient compliance.

PMID- 25057985
TI  - Sickle cell disease patients with and without extremely high hospital use: pain,
      opioids, and coping.
AB  - CONTEXT: Patients with sickle cell disease (SCD) and extremely high hospital use
      (EHHU) encounter significant challenges in pain management because of opioid
      medication use for pain and providers' concerns about addiction. OBJECTIVES: To
      characterize engagement with the health care system surrounding opioid pain
      management among SCD patients with EHHU by comparing their experiences with low
      hospital-using (LHU) patients and their medical providers' perspectives. METHODS:
      One-on-one, semistructured qualitative interviews with patients and medical
      providers were audiotaped and transcribed. Participants were eight SCD patients
      with EHHU; matched by age, gender, and hemoglobinopathy type with eight SCD
      patients with low hospital use; and five providers identified by patients with
      EHHU as important to their care. A multidisciplinary team conducted chart review,
      created narrative summaries from the interviews, and used qualitative software to
      code transcripts based on themes. RESULTS: High-hospital-using patients and LHU
      patients had similar descriptions of their experience of pain and pain management
      with opioids. Patients and medical providers shared concerns about addiction. LHU
      patients described themselves as allies using specific interpersonal and symptom
      related strategies, whereas high-hospital-using patients took a defensive and
      reactive stance toward their providers, who were similarly defensive about their
      care. CONCLUSION: The prescription of opioid medications for SCD pain management
      exacerbates issues of distrust in the patient-provider relationship. Such issues
      dominate patient care in patients with EHHU. Patients with EHHU and providers may
      learn from the proactive nature of LHU patients' engagement with the health care
      system as further research and interventions are designed for EHHU.

PMID- 25057986
TI  - Validation of the Quality of Dying-Hospice Scale.
AB  - CONTEXT: Measuring the quality of dying (QOD) experience is important for hospice
      providers. However, few instruments exist that assess one's QOD; and those that
      do have not been well validated in hospice. OBJECTIVES: This study tested the
      properties of the QOD-Hospice Scale (QOD-Hospice) to provide preliminary
      validation data on internal consistency, inter-rater reliability, convergent
      validity, and factorability in a hospice setting. Additionally, results of the
      factor analysis were used to create a brief version of the measure. METHODS:
      Bereaved informal caregivers who had provided care for a hospice patient were
      recruited from a large nonprofit hospice. Participants completed post-death
      surveys, which included the QOD-Hospice and other study measures. Convergent
      validity was tested by exploring hypothesized associations with related
      instruments measuring negative emotional states (Depression Anxiety Stress Scale
      21), emotional grief (Texas Revised Inventory of Grief-2), social support (Lubben
      Social Network Scale-6), and a single-item measure of satisfaction with hospice
      care. RESULTS: A total of 70 caregivers participated in the survey (40 primary
      and 30 secondary caregivers), most of whom were female (67%) and white (81%). The
      QOD-Hospice produced an alpha of 0.86, an intraclass correlation of 0.49 between
      caregivers of the same decedent, and was correlated with all measures testing
      convergent validity (P<0.05; in the hypothesized direction) and most, but not
      all, subscales. An exploratory factor analysis elicited two factors, Preparation
      (seven items) and Security (six items), which were combined to create a 13-item
      version of the scale, the QOD-Hospice-Short Form. CONCLUSION: Although further
      testing of the QOD-Hospice measures is needed, preliminary evidence suggests that
      the instruments are reliable and valid for use in hospice.

PMID- 25057987
TI  - The quality imperative for palliative care.
AB  - Palliative medicine must prioritize the routine assessment of the quality of
      clinical care we provide. This includes regular assessment, analysis, and
      reporting of data on quality. Assessment of quality informs opportunities for
      improvement and demonstrates to our peers and ourselves the value of our efforts.
      In fact, continuous messaging of the value of palliative care services is needed
      to sustain our discipline; this requires regularly evaluating the quality of our
      care. As the reimbursement mechanisms for health care in the U.S. shift from fee
      for-service to fee-for-value models, palliative care will be expected to report
      robust data on quality of care. We must move beyond demonstrating to our
      constituents (including patients and referrers), "here is what we do," and
      increase the focus on "this is how well we do it" and "let us see how we can do
      it better." It is incumbent on palliative care professionals to lead these
      efforts. This involves developing standardized methods to collect data without
      adding additional burden, comparing and sharing our experiences to promote
      discipline-wide quality assessment and improvement initiatives, and demonstrating
      our intentions for quality improvement on the clinical frontline. 

PMID- 25057988
TI  - Web-based computational chemistry education with CHARMMing I: Lessons and
      tutorial.
AB  - This article describes the development, implementation, and use of web-based
      "lessons" to introduce students and other newcomers to computer simulations of
      biological macromolecules. These lessons, i.e., interactive step-by-step
      instructions for performing common molecular simulation tasks, are integrated
      into the collaboratively developed CHARMM INterface and Graphics (CHARMMing) web
      user interface (http://www.charmming.org). Several lessons have already been
      developed with new ones easily added via a provided Python script. In addition to
      CHARMMing's new lessons functionality, web-based graphical capabilities have been
      overhauled and are fully compatible with modern mobile web browsers (e.g., phones
      and tablets), allowing easy integration of these advanced simulation techniques
      into coursework. Finally, one of the primary objections to web-based systems like
      CHARMMing has been that "point and click" simulation set-up does little to teach
      the user about the underlying physics, biology, and computational methods being
      applied. In response to this criticism, we have developed a freely available
      tutorial to bridge the gap between graphical simulation setup and the technical
      knowledge necessary to perform simulations without user interface assistance. 

PMID- 25057989
TI  - A crucial role for CDC42 in senescence-associated inflammation and
      atherosclerosis.
AB  - Risk factors for atherosclerosis accelerate the senescence of vascular
      endothelial cells and promote atherogenesis by inducing vascular inflammation. A
      hallmark of endothelial senescence is the persistent up-regulation of pro
      inflammatory genes. We identified CDC42 signaling as a mediator of chronic
      inflammation associated with endothelial senescence. Inhibition of CDC42 or NF
      kappaB signaling attenuated the sustained up-regulation of pro-inflammatory genes
      in senescent human endothelial cells. Endothelium-specific activation of the
      p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of
      pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in
      endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly
      attenuated chronic inflammation and plaque formation in atherosclerotic mice.
      While inhibition of NF-kappaB suppressed the pro-inflammatory responses in acute
      inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc
      42 significantly down-regulated pro-inflammatory gene expression and restored the
      shortened lifespan to normal in mutant worms with enhanced inflammation. These
      findings indicate that the CDC42 pathway is critically involved in senescence
      associated inflammation and could be a therapeutic target for chronic
      inflammation in patients with age-related diseases without compromising host
      defenses. 

PMID- 25057991
TI  - Routine cervical dilatation during elective caesarean section. Should we
      continue?
AB  - The caesarean section rate is on the increase globally, with its attendant
      complications. One of the measures adopted by obstetricians to decrease
      complications, such as endometritis and blood loss is intraoperative cervical
      dilatation during elective caesarean section. A multicentre double blind
      randomised controlled trial was carried out in Enugu, Nigeria, to ascertain the
      usefulness of this practice. A total of 208 pregnant women were randomised: 104
      had intraoperative cervical dilatation and the other 104 did not have their
      cervices dilated. All the patients had similar preoperative, intraoperative and
      postoperative care and were followed up to 6 weeks postpartum. There was no
      significant difference between the two groups. In conclusion, the study shows no
      benefit in routine intraoperative cervical dilation. Practitioners must make sure
      that neither the placenta nor fetal membrane is overlying the internal os before
      they close the uterine wound.

PMID- 25057990
TI  - Gene networks of fully connected triads with complete auto-activation enable
      multistability and stepwise stochastic transitions.
AB  - Fully-connected triads (FCTs), such as the Oct4-Sox2-Nanog triad, have been
      implicated as recurring transcriptional motifs embedded within the regulatory
      networks that specify and maintain cellular states. To explore the possible
      connections between FCT topologies and cell fate determinations, we employed
      computational network screening to search all possible FCT topologies for
      multistability, a dynamic property that allows the rise of alternate regulatory
      states from the same transcriptional network. The search yielded a hierarchy of
      FCTs with various potentials for multistability, including several topologies
      capable of reaching eight distinct stable states. Our analyses suggested that
      complete auto-activation is an effective indicator for multistability, and, when
      gene expression noise was incorporated into the model, the networks were able to
      transit multiple states spontaneously. Different levels of stochasticity were
      found to either induce or disrupt random state transitioning with some
      transitions requiring layovers at one or more intermediate states. Using this
      framework we simulated a simplified model of induced pluripotency by including
      constitutive overexpression terms. The corresponding FCT showed random state
      transitioning from a terminal state to the pluripotent state, with the temporal
      distribution of this transition matching published experimental data. This work
      establishes a potential theoretical framework for understanding cell fate
      determinations by connecting conserved regulatory modules with network dynamics.
      Our results could also be employed experimentally, using established
      developmental transcription factors as seeds, to locate cell lineage
      specification networks by using auto-activation as a cipher. 

PMID- 25057992
TI  - Microbial egress: a hitchhiker's guide to freedom.

PMID- 25058000
TI  - Tumor heterogeneity has important consequences for personalized medicine in
      ovarian cancer.
AB  - Most patients with ovarian cancers relapse, and treatment failure has often been
      attributed to chemoresistance in tumor cells. Emerging evidence indicates that
      tumor heterogeneity may play an equally important role. Although the idea of
      tumor heterogeneity is not new, little attention has been focused on applying it
      to understand and control ovarian cancer progression. Recent advances in
      understanding its generation model, original basis, consequent problems, and
      derived therapies provide great potential for tumor heterogeneity to be a new
      insight in treatment of ovarian cancers.

PMID- 25057993
TI  - The prevalence of primary angle closure glaucoma in adult Asians: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Primary angle closure glaucoma (PACG) is higher in Asians than
      Europeans and Africans, with over 80% of PACG worldwide in Asia. Previous
      estimates of PACG were based largely on early studies, mostly using inappropriate
      case definitions. Therefore, we did a systematic review and meta-analysis to
      estimate the prevalence of PACG in adult Asian populations and to quantify its
      association with age, gender, and region. METHODS: All primary reports of
      population-based studies that reported the prevalence of PACG in adult Asian
      populations were identified. PACG case definition was compatible with the ISGEO
      definition. Twenty-nine population-based studies were included. The overall
      pooled prevalence estimates were calculated using a random effect model, and
      ethnicity-, age- and gender-specific pooled prevalence estimates were also
      calculated. RESULTS: The overall pooled prevalence of PACG in those of adult
      Asians was 0.75% (95% CI, 0.58, 0.96). Ethnicity-specific pooled prevalence
      estimates were 0.97% (0.22, 4.27) in Middle East group, 0.66% (0.23, 1.86) in
      South East Asia group, 0.46% (0.32, 0.64) in India group, 1.10% (0.85, 1.44) in
      China group, and 1.19% (0.35, 3.98) in Japan group, respectively. Age-specific
      prevalence was 0.21% (0.12, 0.37) for those 40-49 years, 0.54% (0.34, 0.85) for
      those 50-59 years, 1.26% (0.93, 1.71) for those 60-69 years, and 2.32% (1.74,
      3.08) for those 70 years or above. The overall female to male ratio of the PACG
      prevalence was 1.51?1 (95% CI 1.01, 2.28). CONCLUSIONS: PACG affects
      approximately 0.75% adult Asians, increasing double per decade, and 60% of cases
      being female. The prevalence rates vary greatly by ethnic region.

PMID- 25058003
TI  - Stimuli-responsive cancer therapy based on nanoparticles.
AB  - Nanoparticles (NPs) have recently been well investigated for cancer therapy.
      Among them, those that are responsive to internal or external stimuli are
      promising due to their flexibility. In this feature article, we provide an
      overview on stimuli-sensitive cancer therapy, using pH- and reduction-sensitive
      NPs, as well as light- and magnetic field-responsive NPs. 

PMID- 25058001
TI  - Characterization of Aedes aegypti innate-immune pathways that limit Chikungunya
      virus replication.
AB  - Replication of arboviruses in their arthropod vectors is controlled by innate
      immune responses. The RNA sequence-specific break down mechanism, RNA
      interference (RNAi), has been shown to be an important innate antiviral response
      in mosquitoes. In addition, immune signaling pathways have been reported to
      mediate arbovirus infections in mosquitoes; namely the JAK/STAT, immune
      deficiency (IMD) and Toll pathways. Very little is known about these pathways in
      response to chikungunya virus (CHIKV) infection, a mosquito-borne alphavirus
      (Togaviridae) transmitted by aedine species to humans resulting in a febrile and
      arthralgic disease. In this study, the contribution of several innate immune
      responses to control CHIKV replication was investigated. In vitro experiments
      identified the RNAi pathway as a key antiviral pathway. CHIKV was shown to
      repress the activity of the Toll signaling pathway in vitro but neither JAK/STAT,
      IMD nor Toll pathways were found to mediate antiviral activities. In vivo data
      further confirmed our in vitro identification of the vital role of RNAi in
      antiviral defence. Taken together these results indicate a complex interaction
      between CHIKV replication and mosquito innate immune responses and demonstrate
      similarities as well as differences in the control of alphaviruses and other
      arboviruses by mosquito immune pathways. 

PMID- 25058002
TI  - Retrieving the intracellular topology from multi-scale protein mobility mapping
      in living cells.
AB  - In living cells, most proteins diffuse over distances of micrometres within
      seconds. Protein translocation is constrained due to the cellular organization
      into subcompartments that impose diffusion barriers and guide enzymatic
      activities to their targets. Here, we introduce an approach to retrieve
      structural features from the scale-dependent mobility of green fluorescent
      protein monomer and multimers in human cells. We measure protein transport
      simultaneously between hundreds of positions by multi-scale fluorescence cross
      correlation spectroscopy using a line-illuminating confocal microscope. From
      these data we derive a quantitative model of the intracellular architecture that
      resembles a random obstacle network for diffusing proteins. This topology
      partitions the cellular content and increases the dwell time of proteins in their
      local environment. The accessibility of obstacle surfaces depends on protein
      size. Our method links multi-scale mobility measurements with a quantitative
      description of intracellular structure that can be applied to evaluate how drug
      induced perturbations affect protein transport and interactions. 

PMID- 25058004
TI  - Performance enhancement of a graphene-zinc phosphide solar cell using the
      electric field-effect.
AB  - The optical transparency and high electron mobility of graphene make it an
      attractive material for photovoltaics. We present a field-effect solar cell using
      graphene to form a tunable junction barrier with an Earth-abundant and low cost
      zinc phosphide (Zn3P2) thin-film light absorber. Adding a semitransparent top
      electrostatic gate allows for tuning of the graphene Fermi level and hence the
      energy barrier at the graphene-Zn3P2 junction, going from an ohmic contact at
      negative gate voltages to a rectifying barrier at positive gate voltages. We
      perform current and capacitance measurements at different gate voltages in order
      to demonstrate the control of the energy barrier and depletion width in the zinc
      phosphide. Our photovoltaic measurements show that the efficiency conversion is
      increased 2-fold when we increase the gate voltage and the junction barrier to
      maximize the photovoltaic response. At an optimal gate voltage of +2 V, we obtain
      an open-circuit voltage of V oc = 0.53 V and an efficiency of 1.9% under AM 1.5 1
      sun solar illumination. This work demonstrates that the field effect can be used
      to modulate and optimize the response of photovoltaic devices incorporating
      graphene.

PMID- 25058005
TI  - Alteration in Mir-21/PTEN expression modulates gefitinib resistance in non-small
      cell lung cancer.
AB  - Resistance to TKI treatment is a major obstacle in effective treatment of NSCLC.
      Besides EGFR mutation status, the mechanisms involved are largely unknown. Some
      evidence supports a role for microRNA 21 in modulating drug sensitivity of
      chemotherapy but its role in NSCLC TKI resistance still remains unexplored. This
      study aimed to investigate whether NSCLC miR-21 mediated resistance to TKIs also
      results from Pten targeting. Here, we show miR-21 promotes cancer by negatively
      regulating Pten expression in human NSCLC tissues: high miR-21 expression levels
      were associated with shorter DFS in 47 NSCLC patients; high miR-21/low Pten
      expression levels indicated a poor TKI clinical response and shorter overall
      survival in another 46 NSCLC patients undergoing TKI treatment. In vitro assays
      showed that miR-21 was up-regulated concomitantly to down-regulation of Pten in
      pc-9/GR cells in comparison with pc-9 cells. Moreover, over-expression of miR-21
      significantly decreased gefitinib sensitivity by down-regulating Pten expression
      and activating Akt and ERK pathways in pc-9 cells, while miR-21 knockdown
      dramatically restored gefitinib sensitivity of pc-9/GR cells by up-regulation of
      Pten expression and inactivation of AKT and ERK pathways, in vivo and in vitro.
      We propose alteration of miR-21/Pten expression as a novel mechanism for TKI
      resistance in NSCLC cancer. Our findings provide a new basis for using miR
      21/Pten-based therapeutic strategies to reverse gefitinib resistance in NSCLC. 

PMID- 25058006
TI  - Effect of vascular formed endothelial cell network on the invasive capacity of
      melanoma using the in vitro 3D co-culture patterning model.
AB  - In vitro three dimensional (3D) cancer models were developed to observe the
      invasive capacity of melanoma cell spheroids co-cultured with the vascular-formed
      endothelial cell network. An array-like multicellular pattern of mouse melanoma
      cell line B16F1 was developed by magnetic cell labeling using a pin-holder device
      for allocation of magnetic force. When the B16F1 patterned together with a
      vascular network of human umbilical vein epithelial cells (HUVEC), spreading and
      progression were observed along the HUVEC network. The B16F1 cells over 80 um
      distance from HUVEC remain in a compact spheroid shape, while B16F1 in the
      proximity of HUVEC aggressively changed their morphology and migrated. The mRNA
      expression levels of IL-6, MDR-1 and MMP-9 in B16F1 increased along with the
      distance the HUVEC network, and these expressions were increased by 5, 3 and 2
      fold in the B16F1 close to HUVEC (within 80 um distance) as compared to that far
      from HUVEC (over 80 um distance). Our results clearly show that malignancy of
      tumor cells is enhanced in proximity to vascular endothelial cells and leads to
      intravasation. 

PMID- 25058007
TI  - Statistical cluster analysis of the British Thoracic Society Severe refractory
      Asthma Registry: clinical outcomes and phenotype stability.
AB  - BACKGROUND: Severe refractory asthma is a heterogeneous disease. We sought to
      determine statistical clusters from the British Thoracic Society Severe
      refractory Asthma Registry and to examine cluster-specific outcomes and
      stability. METHODS: Factor analysis and statistical cluster modelling was
      undertaken to determine the number of clusters and their membership (N = 349).
      Cluster-specific outcomes were assessed after a median follow-up of 3 years. A
      classifier was programmed to determine cluster stability and was validated in an
      independent cohort of new patients recruited to the registry (n = 245). FINDINGS:
      Five clusters were identified. Cluster 1 (34%) were atopic with early onset
      disease, cluster 2 (21%) were obese with late onset disease, cluster 3 (15%) had
      the least severe disease, cluster 4 (15%) were the eosinophilic with late onset
      disease and cluster 5 (15%) had significant fixed airflow obstruction. At follow
      up, the proportion of subjects treated with oral corticosteroids increased in all
      groups with an increase in body mass index. Exacerbation frequency decreased
      significantly in clusters 1, 2 and 4 and was associated with a significant fall
      in the peripheral blood eosinophil count in clusters 2 and 4. Stability of
      cluster membership at follow-up was 52% for the whole group with stability being
      best in cluster 2 (71%) and worst in cluster 4 (25%). In an independent
      validation cohort, the classifier identified the same 5 clusters with similar
      patient distribution and characteristics. INTERPRETATION: Statistical cluster
      analysis can identify distinct phenotypes with specific outcomes. Cluster
      membership can be determined using a classifier, but when treatment is optimised,
      cluster stability is poor.

PMID- 25058009
TI  - Implications of central venous catheters in patients with stage D heart failure
      who are stable but inotrope dependent.

PMID- 25058010
TI  - Brain bases of reading fluency in typical reading and impaired fluency in
      dyslexia.
AB  - Although the neural systems supporting single word reading are well studied,
      there are limited direct comparisons between typical and dyslexic readers of the
      neural correlates of reading fluency. Reading fluency deficits are a persistent
      behavioral marker of dyslexia into adulthood. The current study identified the
      neural correlates of fluent reading in typical and dyslexic adult readers, using
      sentences presented in a word-by-word format in which single words were presented
      sequentially at fixed rates. Sentences were presented at slow, medium, and fast
      rates, and participants were asked to decide whether each sentence did or did not
      make sense semantically. As presentation rates increased, participants became
      less accurate and slower at making judgments, with comprehension accuracy
      decreasing disproportionately for dyslexic readers. In-scanner performance on the
      sentence task correlated significantly with standardized clinical measures of
      both reading fluency and phonological awareness. Both typical readers and readers
      with dyslexia exhibited widespread, bilateral increases in activation that
      corresponded to increases in presentation rate. Typical readers exhibited
      significantly larger gains in activation as a function of faster presentation
      rates than readers with dyslexia in several areas, including left prefrontal and
      left superior temporal regions associated with semantic retrieval and semantic
      and phonological representations. Group differences were more extensive when
      behavioral differences between conditions were equated across groups. These
      findings suggest a brain basis for impaired reading fluency in dyslexia,
      specifically a failure of brain regions involved in semantic retrieval and
      semantic and phonological representations to become fully engaged for
      comprehension at rapid reading rates. 

PMID- 25058011
TI  - Pooled analysis of non-union, re-operation, infection, and approach related
      complications after anterior odontoid screw fixation.
AB  - BACKGROUND: Anterior odontoid screw fixation (AOSF) has been one of the most
      popular treatments for odontoid fractures. However, the true efficacy of AOSF
      remains unclear. In this study, we aimed to provide the pooled rates of non
      union, reoperation, infection, and approach related complications after AOSF for
      odontoid fractures. METHODS: We searched studies that discussed complications
      after AOSF for type II or type III odontoid fractures. A proportion meta-analysis
      was done and potential sources of heterogeneity were explored by meta-regression
      analysis. RESULTS: Of 972 references initially identified, 63 were eligible for
      inclusion. 54 studies provided data regarding non-union. The pooled non-union
      rate was 10% (95% CI: 7%-3%). 48 citations provided re-operation information with
      a pooled proportion of 5% (95% CI: 3%-7%). Infection was described in 20 studies
      with an overall rate of 0.2% (95% CI: 0%-1.2%). The main approach related
      complication is postoperative dysphagia with a pooled rate of 10% (95% CI: 4%
      17%). Proportions for the other approach related complications such as
      postoperative hoarseness (1.2%, 95% CI: 0%-3.7%), esophageal/retropharyngeal
      injury (0%, 95% CI: 0%-1.1%), wound hematomas (0.2%, 95% CI: 0%-1.8%), and spinal
      cord injury (0%, 95% CI: 0%-0.2%) were very low. Significant heterogeneities were
      detected when we combined the rates of non-union, re-operation, and dysphagia.
      Multivariate meta-regression analysis showed that old age was significantly
      predictive of non-union. Subgroup comparisons showed significant higher non-union
      rates in age >= 70 than that in age <= 40 and in age 40 to <50. Meta-regression
      analysis did not reveal any examined variables influencing the re-operation rate.
      Meta-regression analysis showed age had a significant effect on the dysphagia
      rate. CONCLUSIONS/SIGNIFICANCES: This study summarized the rates of non-union,
      reoperation, infection, and approach related complications after AOSF for
      odontoid fractures. Elderly patients were more likely to experience non-union and
      dysphagia.

PMID- 25058012
TI  - Identification of differentially expressed genes in flax (Linum usitatissimum L.)
      under saline-alkaline stress by digital gene expression.
AB  - The salinization and alkalization of soil are widespread environmental problems,
      and alkaline salt stress is more destructive than neutral salt stress. Therefore,
      understanding the mechanism of plant tolerance to saline-alkaline stress has
      become a major challenge. However, little attention has been paid to the
      mechanism of plant alkaline salt tolerance. In this study, gene expression
      profiling of flax was analyzed under alkaline-salt stress (AS2), neutral salt
      stress (NSS) and alkaline stress (AS) by digital gene expression. Three-week-old
      flax seedlings were placed in 25 mM Na2CO3 (pH11.6) (AS2), 50mM NaCl (NSS) and
      NaOH (pH11.6) (AS) for 18 h. There were 7736, 1566 and 454 differentially
      expressed genes in AS2, NSS and AS compared to CK, respectively. The GO category
      gene enrichment analysis revealed that photosynthesis was particularly affected
      in AS2, carbohydrate metabolism was particularly affected in NSS, and the
      response to biotic stimulus was particularly affected in AS. We also analyzed the
      expression pattern of five categories of genes including transcription factors,
      signaling transduction proteins, phytohormones, reactive oxygen species proteins
      and transporters under these three stresses. Some key regulatory gene families
      involved in abiotic stress, such as WRKY, MAPKKK, ABA, PrxR and ion channels,
      were differentially expressed. Compared with NSS and AS, AS2 triggered more
      differentially expressed genes and special pathways, indicating that the
      mechanism of AS2 was more complex than NSS and AS. To the best of our knowledge,
      this was the first transcriptome analysis of flax in response to saline-alkaline
      stress. These data indicate that common and diverse features of saline-alkaline
      stress provide novel insights into the molecular mechanisms of plant saline
      alkaline tolerance and offer a number of candidate genes as potential markers of
      tolerance to saline-alkaline stress.

PMID- 25058014
TI  - Electrophysiological correlates of mental navigation in blind and sighted people.
AB  - The aim of the present study was to investigate functional reorganization of the
      occipital cortex for a mental navigation task in blind people. Eight completely
      blind adults and eight sighted matched controls performed a mental navigation
      task, in which they mentally imagined to walk along familiar routes of their
      hometown during a multi-channel EEG measurement. A motor imagery task was used as
      control condition. Furthermore, electrophysiological activation patterns during a
      resting measurement with open and closed eyes were compared between blind and
      sighted participants. During the resting measurement with open eyes, no
      differences in EEG power were observed between groups, whereas sighted
      participants showed higher alpha (8-12Hz) activity at occipital sites compared to
      blind participants during an eyes-closed resting condition. During the mental
      navigation task, blind participants showed a stronger event-related
      desynchronization in the alpha band over the visual cortex compared to sighted
      controls indicating a stronger activation in this brain region in the blind.
      Furthermore, groups showed differences in functional brain connectivity between
      fronto-central and parietal-occipital brain networks during mental navigation
      indicating stronger visuo-spatial processing in sighted than in blind people
      during mental navigation. Differences in electrophysiological parameters between
      groups were specific for mental navigation since no group differences were
      observed during motor imagery. These results indicate that in the absence of
      vision the visual cortex takes over other functions such as spatial navigation. 

PMID- 25058013
TI  - The global burden of disease study 2010: interpretation and implications for the
      neglected tropical diseases.

PMID- 25058016
TI  - Risk of head and neck cancer in patients with diabetes mellitus: a retrospective
      cohort study in Taiwan.
AB  - IMPORTANCE: An increasing body of evidence suggests that certain types of cancers
      are more common in people with diabetes mellitus (DM). However, the risk of head
      and neck cancer (HNC) in patients with DM has seldom been explored. OBJECTIVE: To
      examine the risk of HNC in patients with DM. DESIGN, SETTING, AND PARTICIPANTS:
      In this retrospective cohort study using Taiwan's Longitudinal Health Insurance
      Research Database, we compared 89,089 patients newly diagnosed as having DM and
      controls without DM-related medical claims matched for comorbidities (obesity,
      coronary artery disease, hyperlipidemia, and hypertension), sex, and age.
      Patients were assessed from the index date until the end of follow-up on December
      31, 2011, or until the patient was censored because of death. MAIN OUTCOMES AND
      MEASURES: The incidence of HNC at the end of 2011. RESULTS: The incidence of HNC
      was 1.47 times higher in patients newly diagnosed as having DM than was the risk
      of a first malignant tumor in the control group (adjusted hazard ratio [AHR],
      1.48; 95% CI, 1.31-1.67). The risks of oral cancer (AHR, 1.74; 95% CI, 1.47
      2.06), oropharyngeal cancer (AHR, 1.53; 95% CI, 1.01-2.31), and nasopharyngeal
      carcinoma (AHR, 1.40; 95% CI, 1.03-1.89) were significantly higher in patients
      with DM than in controls. CONCLUSIONS AND RELEVANCE: Diabetes is associated with
      an increased risk of developing HNC. The risks of developing oral cavity cancer,
      oropharyngeal cancer, and nasopharyngeal carcinoma were significantly higher in
      patients with DM.

PMID- 25058015
TI  - Wnt signaling interacts with bmp and edn1 to regulate dorsal-ventral patterning
      and growth of the craniofacial skeleton.
AB  - Craniofacial development requires signals from epithelia to pattern skeletogenic
      neural crest (NC) cells, such as the subdivision of each pharyngeal arch into
      distinct dorsal (D) and ventral (V) elements. Wnt signaling has been implicated
      in many aspects of NC and craniofacial development, but its roles in D-V arch
      patterning remain unclear. To address this we blocked Wnt signaling in zebrafish
      embryos in a temporally-controlled manner, using transgenics to overexpress a
      dominant negative Tcf3, (dntcf3), (Tg(hsp70I:tcf3-GFP), or the canonical Wnt
      inhibitor dickkopf1 (dkk1), (Tg(hsp70i:dkk1-GFP) after NC migration. In dntcf3
      transgenics, NC cells in the ventral arches of heat-shocked embryos show reduced
      proliferation, expression of ventral patterning genes (hand2, dlx3b, dlx5a,
      msxe), and ventral cartilage differentiation (e.g. lower jaws). These D-V
      patterning defects resemble the phenotypes of zebrafish embryos lacking Bmp or
      Edn1 signaling, and overexpression of dntcf3 dramatically reduces expression of a
      subset of Bmp receptors in the arches. Addition of ectopic BMP (or EDN1) protein
      partially rescues ventral development and expression of dlx3b, dlx5a, and msxe in
      Wnt signaling-deficient embryos, but surprisingly does not rescue hand2
      expression. Thus Wnt signaling provides ventralizing patterning cues to arch NC
      cells, in part through regulation of Bmp and Edn1 signaling, but independently
      regulates hand2. Similarly, heat-shocked dkk1+ embryos exhibit ventral arch
      reductions, but also have mandibular clefts at the ventral midline not seen in
      dntcf3+ embryos. Dkk1 is expressed in pharyngeal endoderm, and cell
      transplantation experiments reveal that dntcf3 must be overexpressed in
      pharyngeal endoderm to disrupt D-V arch patterning, suggesting that distinct
      endodermal roles for Wnts and Wnt antagonists pattern the developing skeleton. 

PMID- 25058017
TI  - Versatile reticular polyethylenimine derivative-mediated targeted drug and gene
      codelivery for tumor therapy.
AB  - The study is aimed to develop a versatile reticular polyethylenimine (PEI)
      derivative eprosartan-g-PEI (ESP) conjugate-mediated targeted drug and gene
      codelivery system for tumor therapy. Eprosartan (ES), an angiotensin II type 1
      receptor blocker (ARB), which has been proven to exert beneficial effects on
      tumor progression, vascularization, and metastasis as the conventional
      antihypertensive drug, was conjugated with PEI-1.8K chains into ESP via a bis
      amide bond of pH-sensitivity to overcome high cytotoxicity and nontargeted gene
      delivery of PEI-25K. P53 gene was encapsulated in the ESP to form the codelivery
      system of ESP/p53 complexes, and this system was comprehensively characterized.
      In vitro ESP/p53 complexes had a significant effect on inhibiting angiogenesis by
      reducing the expression and secretion of VEGF. In vivo the effective antitumor
      activity of ESP/p53 complexes was observed on nude mice bearing PANC-1
      xenografts, and the microvessel density (MVD) examination demonstrated that
      ESP/p53 complex-produced antitumor efficacy was closely correlated with the
      efficient angiogenesis repression. These findings disclosed that the
      multifunctional ESP/p53 complexes might be a promising dual anticancer drug and
      gene codelivery system. 

PMID- 25058018
TI  - Reply: To PMID 25051058.

PMID- 25058019
TI  - Training the competent colonoscopist.

PMID- 25058020
TI  - Theoretical study of the CsNa molecule: adiabatic and diabatic potential energy
      and dipole moment.
AB  - The adiabatic and diabatic potential energy curves of the low-lying electronic
      states of the NaCs molecule dissociating into Na (3s, 3p) + Cs (6s, 6p, 5d, 7s,
      7p, 6d, 8s, 4f) have been investigated. The molecular calculations are performed
      using an ab initio approach based on nonempirical pseudopotential, parametrized l
      dependent polarization potentials and full configuration interaction calculations
      through the CIPCI quantum chemistry package. The derived spectroscopic constants
      (Re, De, Te, omegae, omegaexe, and Be) of the ground state and lower excited
      states are compared with the available theoretical and experimental works.
      Moreover, accurate permanent and transition dipole moment have been determined as
      a function of the internuclear distance. The adiabatic permanent dipole moment
      for the first nine (1)Sigma(+) electronic states have shown both ionic characters
      associated with electron transfer related to Cs(+)Na(-) and Cs(-)Na(+)
      arrangements. By a simple rotation, the diabatic permanent dipole moment is
      determined and has revealed a linear behavior, particularly at intermediate and
      large distances. Many peaks around the avoided crossing locations have been
      observed for the transition dipole moment between neighbor electronic states. 

PMID- 25058021
TI  - Phase-coherence transitions and communication in the gamma range between delay
      coupled neuronal populations.
AB  - Synchronization between neuronal populations plays an important role in
      information transmission between brain areas. In particular, collective
      oscillations emerging from the synchronized activity of thousands of neurons can
      increase the functional connectivity between neural assemblies by coherently
      coordinating their phases. This synchrony of neuronal activity can take place
      within a cortical patch or between different cortical regions. While short-range
      interactions between neurons involve just a few milliseconds, communication
      through long-range projections between different regions could take up to tens of
      milliseconds. How these heterogeneous transmission delays affect communication
      between neuronal populations is not well known. To address this question, we have
      studied the dynamics of two bidirectionally delayed-coupled neuronal populations
      using conductance-based spiking models, examining how different synaptic delays
      give rise to in-phase/anti-phase transitions at particular frequencies within the
      gamma range, and how this behavior is related to the phase coherence between the
      two populations at different frequencies. We have used spectral analysis and
      information theory to quantify the information exchanged between the two
      networks. For different transmission delays between the two coupled populations,
      we analyze how the local field potential and multi-unit activity calculated from
      one population convey information in response to a set of external inputs applied
      to the other population. The results confirm that zero-lag synchronization
      maximizes information transmission, although out-of-phase synchronization allows
      for efficient communication provided the coupling delay, the phase lag between
      the populations, and the frequency of the oscillations are properly matched. 

PMID- 25058022
TI  - Comparative analysis of human mitochondrial methylomes shows distinct patterns of
      epigenetic regulation in mitochondria.
AB  - DNA methylation and histone modifications across the nuclear genome have been
      extensively analyzed, but the epigenetic modifications associated with the
      mitochondrial genome have not yet been analyzed at high resolutions. In the
      present work, we analyzed methyl-cytosine profiles from methylated DNA
      immunoprecipitation datasets from 39 different human cell and tissue types from
      the NIH Roadmap Epigenomics project and validated the data using an orthologous
      bisulfite sequencing dataset. We observe a distinct distribution of zmethyl
      cytosine in mitochondrial genomes which are conserved across all cell and tissue
      types. This study thus describes the first comprehensive map of methyl cytosines
      across the human mitochondrial genome. 

PMID- 25058023
TI  - Pasture characteristics in three different ecotypes at Khovd Aimag, Western
      Mongolia.
AB  - The transition of nomadic pastoralism to more sessile forms of rangeland
      utilization and increased stocking rates can result in the degradation of
      pasture. After political changes in the 1990s in Mongolia, population growth and
      missing alternative livelihoods intensified the grazing pressure on pastures, and
      further decreased the condition of the fragile arid ecosystems. To learn more
      about the productivity and quality of pasture land in Khovd Aimag in the western
      region of Mongolia, standing biomass was measured in the alpine region, mountain
      steppe and semi-desert. Plant samples were analyzed for nitrogen and fiber
      contents by wet chemistry and Near Infrared Spectroscopy (NIRS). Results show
      clear differences in distribution of biomass with reduced biomass in the vicinity
      of temporary settlements. From July to early September plant nitrogen contents
      decreased in the alpine region, remained unchanged in the mountain steppe and
      increased in the semi-desert. Nitrogen concentrations were elevated in vegetation
      close to temporary settlements. For fiber contents (ADF) no clear patterns were
      found. Neither biomass/m(2) nor vegetation cover were appropriate indicators for
      food quality.

PMID- 25058024
TI  - The Miller's knot as an alternative to the surgical knotting? Characterization of
      the mechanical behavior.
AB  - Several types of materials and surgical suture patterns are used in conventional
      surgery. Their combination with an appropriate knot is the basis for correct
      tissue apposition and healing. Knot security is essential to prevent loosening or
      slipping before the suture line is completely closed. Nevertheless, the knot
      itself is the weakest link in any surgical handling. The aim of this study is to
      determine and compare the mechanical behavior of four surgical knot types (square
      knot, surgeon's knot, square slipknot and Miller's knot) performed with three
      different suture materials (absorbable monofilament glyconate, non-absorbable
      monofilament polyamide and absorbable braided polyglycolic acid) in a non
      biological experimental in vitro model (a tube of synthetic material with non
      linear mechanical behavior). The mechanical properties of each suture material
      are also compared. Ten samples were mechanically tested for each suture and knot
      using a uniaxial tensile test until complete sample rupture. The failure Cauchy
      stress and stretch were calculated. The Cauchy stress at 5%, 10% and 15% strain
      and standard deviation were compared for each suture and knot type. The results
      demonstrated that all the suture materials had statistically significant
      differences in their non-linear mechanical behavior. Absorbable monofilament
      glyconate was the most compliant suture with the greatest tensile strength, while
      absorbable braided polyglycolic acid was the stiffest. Regardless of the suture
      type used, the Miller's knot had the greatest failure Cauchy stress and stretch,
      while the square, surgeon's and square slipknot had the lowest. In all cases, the
      Miller's knot was more compliant and had greater tensile strength than the other
      knots. The square knot, surgeon's knot, and square slipknot had statistically
      significant similarities in their mechanical behavior. Therefore, the Miller's
      knot could be classified as the gold standard and an alternative to the surgical
      knotting. 

PMID- 25058025
TI  - Classification of selectively constrained DNA elements using feature vectors and
      rule-based classifiers.
AB  - Scarce work has been done in the analysis of the composition of conserved non
      coding elements (CNEs) that are identified by comparisons of two or more genomes
      and are found to exist in all metazoan genomes. Here we present the analysis of
      CNEs with a methodology that takes into account word occurrence at various
      lengths scales in the form of feature vector representation and rule based
      classifiers. We implement our approach on both protein-coding exons and CNEs,
      originating from human, insect (Drosophila melanogaster) and worm (Caenorhabditis
      elegans) genomes, that are either identified in the present study or obtained
      from the literature. Alignment free feature vector representation of sequences
      combined with rule-based classification methods leads to successful
      classification of the different CNEs classes. Biologically meaningful results are
      derived by comparison with the genomic signatures approach, and classification
      rates for a variety of functional elements of the genomes along with surrogates
      are presented. 

PMID- 25058026
TI  - Exogenous electron shuttle-mediated extracellular electron transfer of Shewanella
      putrefaciens 200: electrochemical parameters and thermodynamics.
AB  - Despite the importance of exogenous electron shuttles (ESs) in extracellular
      electron transfer (EET), a lack of understanding of the key properties of ESs is
      a concern given their different influences on EET processes. Here, the ES
      mediated EET capacity of Shewanella putrefaciens 200 (SP200) was evaluated by
      examining the electricity generated in a microbial fuel cell. The results
      indicated that all the ESs substantially accelerated the current generation
      compared to only SP200. The current and polarization parameters were linearly
      correlated with both the standard redox potential (E(ES)(0)) and the electron
      accepting capacity (EAC) of the ESs. A thermodynamic analysis of the electron
      transfer from the electron donor to the electrode suggested that the EET from c
      type cytochromes (c-Cyts) to ESs is a crucial step causing the differences in EET
      capacities among various ESs. Based on the derived equations, both E(ES)(0) and
      EAC can quantitatively determine potential losses (DeltaE) that reflect the
      potential loss of the ES-mediated EET. In situ spectral kinetic analysis of ES
      reduction by c-Cyts in a living SP200 suspension was first investigated with the
      E(ES), E(c-Cyt), and DeltaE values being calculated. This study can provide a
      comprehensive understanding of the role of ESs in EET.

PMID- 25058028
TI  - Health services research: opportunities for pathology.
AB  - This Guest Editorial advocates for expanded health services research in the field
      of pathology. 

PMID- 25058027
TI  - Mammalian target of rapamycin complex 1 and cyclooxygenase 2 pathways
      cooperatively exacerbate endometrial cancer.
AB  - The underlying causes of endometrial cancer (EMC) are poorly understood, and
      treatment options for patients with advanced stages of the disease are limited.
      Mutations in the phosphatase and tensin homologue gene are frequently detected in
      EMC. Cyclooxygenase 2 (Cox2) and mammalian target of rapamycin complex 1 (mTORC1)
      are known downstream targets of the phosphatase and tensin homologue protein, and
      their activities are up-regulated in EMC. However, it is not clear whether Cox2
      and mTORC1 are crucial players in cancer progression or whether they work in
      parallel or cooperatively. In this study, we used a Cox2 inhibitor, celecoxib,
      and an mTORC1 inhibitor, rapamycin, in mouse models of EMC and in human EMC cell
      lines to explore the interactive roles of Cox2 and mTORC1 signaling. We found
      that a combined treatment with celecoxib and rapamycin markedly reduces EMC
      progression. We also observed that rapamycin reduces Cox2 expression, whereas
      celecoxib reduces mTORC1 activity. These results suggest that Cox2 and mTORC1
      signaling is cross-regulated and cooperatively exacerbate EMC. 

PMID- 25058029
TI  - Pto kinase binds two domains of AvrPtoB and its proximity to the effector E3
      ligase determines if it evades degradation and activates plant immunity.
AB  - The tomato--Pseudomonas syringae pv. tomato (Pst)--pathosystem is one of the best
      understood models for plant-pathogen interactions. Certain wild relatives of
      tomato express two closely related members of the same kinase family, Pto and
      Fen, which recognize the Pst virulence protein AvrPtoB and activate effector
      triggered immunity (ETI). AvrPtoB, however, contains an E3 ubiquitin ligase
      domain in its carboxyl terminus which causes degradation of Fen and undermines
      its ability to activate ETI. In contrast, Pto evades AvrPtoB-mediated degradation
      and triggers ETI in response to the effector. It has been reported recently that
      Pto has higher kinase activity than Fen and that this difference allows Pto to
      inactivate the E3 ligase through phosphorylation of threonine-450 (T450) in
      AvrPtoB. Here we show that, in contrast to Fen which can only interact with a
      single domain proximal to the E3 ligase of AvrPtoB, Pto binds two distinct
      domains of the effector, the same site as Fen and another N-terminal domain. In
      the absence of E3 ligase activity Pto binds to either domain of AvrPtoB to
      activate ETI. However, the presence of an active E3 ligase domain causes
      ubiquitination of Pto that interacts with the domain proximal to the E3 ligase,
      identical to ubiquitination of Fen. Only when Pto binds its unique distal domain
      can it resist AvrPtoB-mediated degradation and activate ETI. We show that
      phosphorylation of T450 is not required for Pto-mediated resistance in vivo and
      that a kinase-inactive version of Pto is still capable of activating ETI in
      response to AvrPtoB. Our results demonstrate that the ability of Pto to interact
      with a second site distal to the E3 ligase domain in AvrPtoB, and not a higher
      kinase activity or T450 phosphorylation, allows Pto to evade ubiquitination and
      to confer immunity to Pst.

PMID- 25058030
TI  - Genomic models of short-term exposure accurately predict long-term chemical
      carcinogenicity and identify putative mechanisms of action.
AB  - BACKGROUND: Despite an overall decrease in incidence of and mortality from
      cancer, about 40% of Americans will be diagnosed with the disease in their
      lifetime, and around 20% will die of it. Current approaches to test carcinogenic
      chemicals adopt the 2-year rodent bioassay, which is costly and time-consuming.
      As a result, fewer than 2% of the chemicals on the market have actually been
      tested. However, evidence accumulated to date suggests that gene expression
      profiles from model organisms exposed to chemical compounds reflect underlying
      mechanisms of action, and that these toxicogenomic models could be used in the
      prediction of chemical carcinogenicity. RESULTS: In this study, we used a rat
      based microarray dataset from the NTP DrugMatrix Database to test the ability of
      toxicogenomics to model carcinogenicity. We analyzed 1,221 gene-expression
      profiles obtained from rats treated with 127 well-characterized compounds,
      including genotoxic and non-genotoxic carcinogens. We built a classifier that
      predicts a chemical's carcinogenic potential with an AUC of 0.78, and validated
      it on an independent dataset from the Japanese Toxicogenomics Project consisting
      of 2,065 profiles from 72 compounds. Finally, we identified differentially
      expressed genes associated with chemical carcinogenesis, and developed novel data
      driven approaches for the molecular characterization of the response to chemical
      stressors. CONCLUSION: Here, we validate a toxicogenomic approach to predict
      carcinogenicity and provide strong evidence that, with a larger set of compounds,
      we should be able to improve the sensitivity and specificity of the predictions.
      We found that the prediction of carcinogenicity is tissue-dependent and that the
      results also confirm and expand upon previous studies implicating DNA damage, the
      peroxisome proliferator-activated receptor, the aryl hydrocarbon receptor, and
      regenerative pathology in the response to carcinogen exposure.

PMID- 25058032
TI  - Molecular transport network security using multi-wavelength optical spins.
AB  - Multi-wavelength generation system using an optical spin within the modified add
      drop optical filter known as a PANDA ring resonator for molecular transport
      network security is proposed. By using the dark-bright soliton pair control, the
      optical capsules can be constructed and applied to securely transport the trapped
      molecules within the network. The advantage is that the dark and bright soliton
      pair (components) can securely propagate for long distance without
      electromagnetic interference. In operation, the optical intensity from PANDA ring
      resonator is fed into gold nano-antenna, where the surface plasmon oscillation
      between soliton pair and metallic waveguide is established. 

PMID- 25058031
TI  - Green biosynthesis of silver nanoparticles using Althaea officinalis radix
      hydroalcoholic extract.
AB  - The objectives were to study the potential of Althaea officinalis radix in
      production of silver NPs, and the effect of the extract ethanol concentration on
      the produced NPs. Seventy and ninety-six percent hydroalcoholic extracts were
      prepared by percolation of the plant powder. The extract was concentrated by
      rotary evaporator and then freeze-dried. Silver ions were determined using atomic
      absorption analysis. The NPs were characterized by Nano-Zeta Sizer and TEM. Both
      of 70% and 96% of hydroalcoholic extracts of A. officinalis radix successfully
      synthesized spherical and poly-dispersed silver NPs. The conversion was fast and
      almost completed in 5 h. 

PMID- 25058033
TI  - Effect of emulsification-diffusion parameters on the formation of poly (3
      hydroxybutyrate-co-3-hydroxyvalerate) particles.
AB  - The aim of this work was to evaluate the effect of various production parameters
      on the formation and particle size of poly (3-hydroxybutyrate-co-3
      hydroxyvalerate) PHBV particles prepared by the emulsification-diffusion
      technique. The increase in homogenization time and speed caused a decrease in
      particle size. No particle formation was observed below 2% (w/v) PHBV in the
      organic phase. Smaller particle size and narrower size distribution were observed
      when polyvinyl alcohol (PVA) was used as a stabilizer, when compared to
      didodecyldimethylammonium bromide. Submicron particles of 531 +/- 150 nm size
      were obtained with 2% (w/v) PVA at 17 500 rpm and 15 min homogenization
      conditions with dichloromethane as the organic solvent. 

PMID- 25058034
TI  - Molecular imaging of peroxynitrite with HKGreen-4 in live cells and tissues.
AB  - Peroxynitrite (ONOO(-)), the product of a radical combination reaction of nitric
      oxide and superoxide, is a potent biological oxidant involved in a broad spectrum
      of physiological and pathological processes. Herein we report the development,
      characterization, and biological applications of a new fluorescent probe, HKGreen
      4, for peroxynitrite detection and imaging. HKGreen-4 utilizes a peroxynitrite
      triggered oxidative N-dearylation reaction to achieve an exceptionally sensitive
      and selective fluorescence turn-on response toward peroxynitrite in chemical
      systems and biological samples. We have thoroughly evaluated the utility of
      HKGreen-4 for intracellular peroxynitrite imaging and, more importantly,
      demonstrated that HKGreen-4 can be efficiently employed to visualize endogenous
      peroxynitrite generated in Escherichia coli-challenged macrophages and in live
      tissues from a mouse model of atherosclerosis. This probe should serve as a
      powerful molecular imaging tool to explore peroxynitrite biology under a variety
      of physiological and pathological contexts.

PMID- 25058035
TI  - Skin manifestation of methylmalonic acidemia: case report and review of the
      literature.
AB  - Skin manifestations, including scalded skin, desquamation, and chronic
      periorificial dermatitis, are rare clinical signs in patients with methylmalonic
      acidemia. This condition may be due to enzyme deficiency or multi-nutrient
      deficiency because of nutritional restriction. Bullous skin lesion is very rare
      in these patients and consequently, this type of skin lesion can be the
      presenting sign of methylmalonic acidemia. 

PMID- 25058036
TI  - Coincident systemic lupus erythematosus and psoriasis vulgaris: a case report.
AB  - Psoriasis vulgaris is an autoimmune chronic inflammatory skin disease, but its
      association with other typical autoimmune disease such as systemic lupus
      erythematosus has only occasionally been reported. We presented a 25-year-old
      female who developed systemic lupus erythematosus associated with psoriasis
      vulgaris. Her conditions were in good control after she got administration of
      prednisolone (5 mg/day) and Tripterygium Wilfordii Hook (20 mg/day). It is
      necessary to integrate past history and physical examination to diagnose
      coincident SLE and psoriasis, and combined treatment with prednisolone and
      Tripterygium Wilfordii Hook proves effective. 

PMID- 25058037
TI  - Erythematous papular eruption in a seven-month-old male.

PMID- 25058038
TI  - Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human
      plasma.
AB  - Carbon monoxide derived from the catalytic action of heme oxygenase-1 or carbon
      monoxide-releasing molecules (CORMs) has been found to potentially be an
      anticoagulant or procoagulant agent. Of interest, two water-soluble CORMs, CORM-3
      and CORM-A1, recently became commercially available. Thus, the purpose of the
      present study was to assess and compare the effects of the previously well
      studied CORM-2 to the effects of CORM-3 and CORM-A1 on coagulation in citrated
      human plasma with thrombelastography. Plasma exposed to CORMs was incubated at 37
      degrees C for at least one carbon monoxide release half-time, and then tissue
      factor-activated coagulation was commenced with calcium addition. CORM-2 and CORM
      3 enhanced the velocity of clot formation and thrombus strength in a similar
      manner, whereas CORM-A1 did not affect coagulation. However, CORM-A1 did diminish
      tissue-type plasminogen activator initiated fibrinolysis. The similarity in
      effect on coagulation by CORM-2 and CORM-3 was likely secondary to the relatively
      inert effect of their ruthenium-containing carrier molecule, whereas the boron
      containing CORM-A1 may have had no effect secondary to boron binding to
      fibrinogen, preventing carbon monoxide-mediated changes in fibrinogen protein
      structure via attached heme group(s). Future investigations with CORMs should
      have special attention to confounding effects of the carrier molecule. 

PMID- 25058039
TI  - Development and pre-clinical evaluation of two LAIV strains against potentially
      pandemic H2N2 influenza virus.
AB  - H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than
      10 years and disappeared from the human population after 1968. Given that people
      born after 1968 are naive to H2N2, that the virus still circulates in wild birds
      and that this influenza subtype has a proven pandemic track record, H2N2 is
      regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we
      developed and tested in mice and ferrets two live attenuated influenza vaccines
      based on the haemagglutinins of the two different H2N2 lineages that circulated
      at the end of the cycle, using the well characterized A/Leningrad/134/17/57
      (H2N2) master donor virus as the backbone. The vaccine strains containing the HA
      and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a
      temperature sensitive and cold adapted phenotype and a reduced reproduction that
      was limited to the respiratory tract of mice, suggesting that the vaccines may be
      safe for use in humans. Both vaccine strains induced haemagglutination inhibition
      titers in mice. Vaccination abolished virus replication in the nose and lung and
      protected mice from weight loss after homologous and heterologous challenge with
      the respective donor wild type strains. In ferrets, the live attenuated vaccines
      induced high virus neutralizing, haemagglutination and neuraminidase inhibition
      titers, however; the vaccine based on the A/California/1/66 wt virus induced
      higher homologous and better cross-reactive antibody responses than the
      A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus
      reduction observed in the throat and nose of ferrets vaccinated with this vaccine
      after challenge with either of the wild type donor viruses. Moreover, both
      vaccines clearly reduced the infection-induced rhinitis observed in placebo
      vaccinated ferrets. The results favor the vaccine based on the A/California/1/66
      isolate, which will be evaluated in a clinical study. 

PMID- 25058040
TI  - Reasons for premature termination of dialectical behavior therapy for inpatients
      with borderline personality disorder.
AB  - Although one of the main aims of dialectical behavior therapy (DBT) for
      borderline personality disorder (BPD) is to increase the retention rates,
      premature termination rates for DBT inpatient programs were found to be over 30%.
      The aim of the study was to identify the reasons for, and to analyze, patient
      characteristics that are associated with premature termination. We studied 541
      inpatients with BPD, who were consecutively admitted for an open-door 3-month DBT
      inpatient treatment in Berlin, Germany. All participants completed several self
      rating measures and participated in clinical interviews. Fourteen percent, who
      did not complete the full 84 days of assigned treatment, were expelled, mainly
      due to treatment-disturbing behaviors, or substance abuse or possession. Nearly
      19% dropped out of treatment, mostly due to lack of motivation, arguments with
      others, and poor tolerance of emotional distress. Using non-parametric
      conditional inference trees, expulsion was associated with anorexia nervosa and
      alcohol abuse, whereas more than 9 suicide attempts, antisocial personality
      disorders, and more than 86 weeks in a psychiatric hospital were risk factors for
      dropout. We discussed measures and interventions that might lead to an adaptation
      of DBT inpatient programs. Future research should examine the symptom course and
      utilization of health-care services of non-completers.

PMID- 25058041
TI  - Evidence of preferential path formation and path memory effect during successive
      infiltration and drainage cycles in uniform sand columns.
AB  - The formation of preferential flow paths in the partially saturated zone, and in
      naturally structured media, is well known. This study examines non-uniform flow
      in uniform sand columns under different pressure and infiltration/drainage
      conditions. Experiments were carried out in a vacuum box, with applied suction
      set to three different heads, and with infiltration fixed at two different flow
      rates. Tailing observed in some conservative tracer breakthrough curves suggests
      the formation of immobile resident water pockets which slowly exchange mass with
      the flowing water fraction. The applied suction controlled the degree of water
      immobilization whereas flow rate had minimal effect on the dynamic behavior.
      Trapping and exchange of water occurred repeatedly during successive infiltration
      and drainage cycles, implying a (hysteretic) memory effect of the previously
      formed preferential flow paths. Flow and solute transport modeling suggests that
      these dynamics can be described by a mobile-immobile model that corroborates
      measurements suggesting preferential flow path formation. These findings have
      implications for the natural attenuation of contaminants in the partially
      saturated zone, but also for the persistence of a contamination source exposed to
      repeated conditions of infiltration and drainage. 

PMID- 25058042
TI  - Uterine artery Doppler flow velocity waveform analysis following uterine fibroid
      embolisation.
AB  - The objective was to evaluate the relation of uterine artery Doppler flow
      pulsatility index (PI) with total uterine volume reduction following bilateral
      embolisation of uterine fibroids by injection of polyvinyl alcohol particles.
      Doppler flow velocity was examined before and within 8 days after embolisation (n
      = 13). Uterine size was assessed by magnetic resonance imaging (MRI) before, and
      at 3 and 6 months after, the procedure. Mean PI values (mean of right and left
      side) obtained before embolisation were negatively related to uterine size (r = 
      0.68, p = 0.010) but not to uterine volume reduction after the procedure. Mean PI
      values after the procedure were related to the percentage decrease in uterine
      volume both at 3 (r = 0.74, p = 0.004) and 6 months (p = 0.73, p = 0.005).
      Doppler ultrasound measures of the uterine arteries may be used to evaluate
      reduction of uterine size following fibroid embolisation. 

PMID- 25058043
TI  - Mitochondrial proteomic analysis reveals the molecular mechanisms underlying
      reproductive toxicity of zearalenone in MLTC-1 cells.
AB  - Zearalenone (ZEA), a Fusarium mycotoxin that contaminates cereal crops worldwide,
      has been shown to affect the male reproductive system and trigger reactive oxygen
      species (ROS) generation. However, the mechanisms of its toxicity have not been
      fully understood. Because mitochondrion is a key organelle involved in producing
      ROS and generating metabolic intermediates for biosynthesis, an iTRAQ-based
      mitoproteomics approach was employed to identify the molecular mechanism of
      zearalenone toxicity using mitochondria of mouse Leydig tumor cells (MLTC-1). A
      total of 2014 nonredundant proteins were identified, among which 1401 proteins
      (69.56%) were overlapped. There were 52 differentially expressed proteins in
      response to ZEA, and they were primarily involved in energy metabolism, molecular
      transport and endocrine-related functions. Consistent with mitochondrial
      proteomic analysis, the ATP and intracellular Ca(2+) levels increased after ZEA
      treatment. The results suggest that lipid metabolism changed significantly after
      low-dose ZEA exposure, resulting in two alterations. One is the increase in
      energy production through promoted fatty acid uptake and beta-oxidation, along
      with excessive oxidative stress; the other is an inhibition of steroidogenesis
      and esterification, possibly resulting in reduced hormone secretion. A
      hypothetical model of ZEA-induced mitochondrial damage is proposed to provide a
      framework for the mechanism of ZEA toxicity. 

PMID- 25058044
TI  - l-DOPA reverses the impairment of Dentate Gyrus LTD in experimental parkinsonism
      via beta-adrenergic receptors.
AB  - Parkinson's disease (PD) patients exhibit motor and non-motor symptoms that
      severely affect quality of life. Cognitive alterations in PD subjects have been
      related to both structural and functional hippocampal changes. Here we
      investigated the effects of the 6-hydroxydopamine (6-OHDA) lesion in the Medial
      Forebrain Bundle (MFB) on the hippocampus focusing on the Dentate Gyrus (DG). In
      vivo microdialysis measurements revealed that the 6-OHDA injection disrupts both
      dopaminergic and noradrenergic transmission in rat DG. In vitro
      electrophysiological recordings showed that these neurochemical alterations were
      accompanied by impairment of long-term depression (LTD) at medial perforant
      path/DG synapses. Furthermore, this alteration was reversed by l-DOPA treatment.
      Notably, the therapeutic effect of l-DOPA on LTD was blocked by the antagonism of
      beta-noradrenergic receptors, but not by dopamine D1 or D2 receptor antagonists.
      Thus, while the dopaminergic transmission does not seem to be implicated in this
      therapeutic effect of l-DOPA, the noradrenergic system plays a central role in
      the synaptic dysfunction of the DG in experimental PD. Our work provides new
      evidence on the role of catecholamines in DG synaptic plasticity and sheds light
      on the possible synaptic mechanisms underlying cognitive deficits in PD.
      Furthermore, our results indicate that l-DOPA exerts a therapeutic effect on the
      parkinsonian brain through different, coexistent, mechanisms. 

PMID- 25058045
TI  - Transient ischemia elicits a sustained enhancement of thrombus development in the
      cerebral microvasculature: effects of anti-thrombotic therapy.
AB  - OBJECTIVE: While transient ischemic attack (TIA) is a well-known harbinger of
      ischemic stroke, the mechanisms that link TIA to subsequent strokes remain poorly
      understood. The overall aim of this study was to determine whether: 1) brief
      periods of transient cerebral ischemia render this tissue more vulnerable to
      thrombus development and 2) antiplatelet agents used in TIA patients alter
      ischemia-induced thrombogenesis. APPROACH & RESULTS: The middle cerebral artery
      of C57BL/6 mice was occluded for 2.5-10min, followed by reperfusion periods of 1
      28days. Intravital microscopy was used to monitor thrombus development in
      cerebral microvessels induced by light/dye photoactivation. Thrombosis was
      quantified as the time to platelet aggregation on the vessel wall and the time
      for complete blood flow cessation. While brief periods of cerebral ischemia were
      not associated with neurological deficits or brain infarction (evaluated after
      1day), it yielded a pronounced and prolonged (up to 28days) acceleration of
      thrombus formation, compared to control (sham) mice. This prothrombotic phenotype
      was not altered by pre- and/or post-treatment of mice with either aspirin (A),
      clopidogrel (C), dipyridamole (D), or atorvastatin (S), or with A+D+S.
      CONCLUSIONS: The increased vulnerability of the cerebral vasculature to thrombus
      development after a brief period of transient ischemia can be recapitulated in a
      murine model. Antiplatelet or antithrombotic agents used in patients with TIA
      show no benefit in this mouse model of brief transient ischemia.

PMID- 25058046
TI  - Cannabinoid receptor type 2 agonist attenuates apoptosis by activation of
      phosphorylated CREB-Bcl-2 pathway after subarachnoid hemorrhage in rats.
AB  - Early brain injury (EBI) which comprises of vasogenic edema and apoptotic cell
      death is an important component of subarachnoid hemorrhage (SAH) pathophysiology.
      This study evaluated whether cannabinoid receptor type 2 (CB2R) agonist, JWH133,
      attenuates EBI after SAH and whether CB2R stimulation reduces pro-apoptotic
      caspase-3 via up-regulation of cAMP response element-binding protein (CREB)-Bcl-2
      signaling pathway. Male Sprague-Dawley rats (n=123) were subjected to SAH by
      endovascular perforation. Rats received vehicle or JWH133 at 1h after SAH.
      Neurological deficits and brain water content were evaluated at 24h after SAH.
      Western blot was performed to quantify phosphorylated CREB (pCREB), Bcl-2, and
      cleaved caspase-3 levels. Neuronal cell death was evaluated with terminal
      deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end
      labeling staining. Additionally, CREB siRNA was administered to manipulate the
      proposed pathway. JWH133 (1.0mg/kg) improved neurological deficits and reduced
      brain water content in left hemisphere 24h after SAH. JWH133 significantly
      increased activated CREB (pCREB) and Bcl-2 levels and significantly decreased
      cleaved caspase-3 levels in left hemisphere 24h after SAH. CREB siRNA reversed
      the effects of treatment. TUNEL positive neurons in the cortex were reduced with
      JWH133 treatment. Thus, CB2R stimulation attenuated EBI after SAH possibly
      through activation of pCREB-Bcl-2 pathway. 

PMID- 25058054
TI  - Deciphering PDT-induced inflammatory responses using real-time FDG-PET in a mouse
      tumour model.
AB  - Dynamic positron emission tomography (PET), combined with constant infusion of 2
      deoxy-2-[(18)F]fluoro-d-glucose (FDG), enables real-time monitoring of transient
      metabolic changes in vivo, which can serve to understand the underlying
      physiology. Here we investigated characteristic changes in the tumour FDG-uptake
      profiles in relation to acute localized inflammatory responses induced by
      photodynamic therapy (PDT). Dynamic PET imaging with constant FDG infusion was
      used with EMT-6 tumour bearing mice. FDG time-activity uptake curves were
      measured simultaneously, in treated and reference tumours, for 3 hours, before,
      during and after PDT light treatment. Inflammation was studied when evoked,
      either by PDT using a trisulfonated porphyrazine photosensitizer, or
      lipopolysaccharide (LPS), and inhibited using indomethacin. The distinct
      transient patterns, characterized by drops and subsequent recovery of tumour FDG
      uptake rates, were also analysed using immunohistochemical markers for apoptosis,
      necrosis, and inflammation. Typical profiles for tumour FDG-uptake, consisted of
      a drop during PDT, followed by a gradual recovery period. Tumours treated with
      LPS, but not with light, showed a continuous increase in FDG-uptake during the 3
      h experimental period. Treatment with indomethacin, inhibited the rise in FDG
      uptake observed with either LPS or PDT. Tumour FDG-uptake profiles correlated
      with necrosis markers during PDT, and inflammatory response markers post-PDT, but
      not with an apoptosis marker at any time during or after PDT. Dynamic FDG-PET
      imaging combined with indomethacin reveals that, the drop in the tumour FDG
      uptake rate during the PDT illumination phase reflects vascular collapse and
      necrosis, while the increased tumour FDG-uptake rate immediately post
      illumination involves an acute localized inflammatory response. Dynamic FDG
      infusion and PET imaging, combined with the use of selective inhibitors, provides
      unique insight for deciphering the complex underlying processes leading to tumour
      response in PDT, and allows for rapid as well as cost effective optimization of
      PDT protocols. 

PMID- 25058047
TI  - Identification of Giardia lamblia DHHC proteins and the role of protein S
      palmitoylation in the encystation process.
AB  - Protein S-palmitoylation, a hydrophobic post-translational modification, is
      performed by protein acyltransferases that have a common DHHC Cys-rich domain
      (DHHC proteins), and provides a regulatory switch for protein membrane
      association. In this work, we analyzed the presence of DHHC proteins in the
      protozoa parasite Giardia lamblia and the function of the reversible S
      palmitoylation of proteins during parasite differentiation into cyst. Two
      specific events were observed: encysting cells displayed a larger amount of
      palmitoylated proteins, and parasites treated with palmitoylation inhibitors
      produced a reduced number of mature cysts. With bioinformatics tools, we found
      nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome.
      These proteins displayed a conserved structure when compared to different
      organisms and are distributed in different monophyletic clades. Although all
      Giardia DHHC proteins were found to be present in trophozoites and encysting
      cells, these proteins showed a different intracellular localization in
      trophozoites and seemed to be differently involved in the encystation process
      when they were overexpressed. dhhc transgenic parasites showed a different
      pattern of cyst wall protein expression and yielded different amounts of mature
      cysts when they were induced to encyst. Our findings disclosed some important
      issues regarding the role of DHHC proteins and palmitoylation during Giardia
      encystation. 

PMID- 25058055
TI  - Modulation of functional network with real-time fMRI feedback training of right
      premotor cortex activity.
AB  - Although the neurofeedback of real-time fMRI can reportedly enable people to gain
      control of the activity in the premotor cortex (PMA) during motor imagery, it is
      unclear how the neurofeedback training of PMA affect the motor network engaged in
      the motor execution (ME) and imagery (MI) task. In this study, we investigated
      the changes in the motor network engaged in both ME and MI task induced by real
      time neurofeedback training of the right PMA. The neurofeedback training induced
      changes in activity of the ME-related motor network as well as alterations in the
      functional connectivity of both the ME-related and MI-related motor networks.
      Especially, the percent signal change of the right PMA in the last training run
      was found to be significantly correlated with the connectivity between the right
      PMA and the left posterior parietal lobe (PPL) during the pre-training MI run,
      post-training MI run and the last training run. Moreover, the increase in the
      tapping frequency was significantly correlated with the increase of connectivity
      between the right cerebellum and the primary motor area/primary sensory area
      (M1/S1) of the ME-related motor network after neurofeedback training. These
      findings show the importance of the connectivity between the right PMA and left
      PPL of the MI network for the up-regulation of the right PMA as well as the
      critical role of connectivity between the right cerebellum and M1/S1 of the ME
      network in improving the behavioral performance. 

PMID- 25058057
TI  - Cognitive control predicted by color vision, and vice versa.
AB  - One of the most important functions of cognitive control is to continuously adapt
      cognitive processes to changing and often conflicting demands of the environment.
      Dopamine (DA) has been suggested to play a key role in the signaling and
      resolution of such response conflict. Given that DA is found in high
      concentration in the retina, color vision discrimination has been suggested as an
      index of DA functioning and in particular blue-yellow color vision impairment
      (CVI) has been used to indicate a central hypodopaminergic state. We used color
      discrimination (indexed by the total color distance score; TCDS) to predict
      individual differences in the cognitive control of response conflict, as
      reflected by conflict-resolution efficiency in an auditory Simon task. As
      expected, participants showing better color discrimination were more efficient in
      resolving response conflict. Interestingly, participants showing a blue-yellow
      CVI were associated with less efficiency in handling response conflict. Our
      findings indicate that color vision discrimination might represent a promising
      predictor of cognitive controlability in healthy individuals. 

PMID- 25058056
TI  - Dynamic changes in network activations characterize early learning of a natural
      language.
AB  - Those who are initially exposed to an unfamiliar language have difficulty
      separating running speech into individual words, but over time will recognize
      both words and the grammatical structure of the language. Behavioral studies have
      used artificial languages to demonstrate that humans are sensitive to
      distributional information in language input, and can use this information to
      discover the structure of that language. This is done without direct instruction
      and learning occurs over the course of minutes rather than days or months.
      Moreover, learners may attend to different aspects of the language input as their
      own learning progresses. Here, we examine processing associated with the early
      stages of exposure to a natural language, using fMRI. Listeners were exposed to
      an unfamiliar language (Icelandic) while undergoing four consecutive fMRI scans.
      The Icelandic stimuli were constrained in ways known to produce rapid learning of
      aspects of language structure. After approximately 4 min of exposure to the
      Icelandic stimuli, participants began to differentiate between correct and
      incorrect sentences at above chance levels, with significant improvement between
      the first and last scan. An independent component analysis of the imaging data
      revealed four task-related components, two of which were associated with
      behavioral performance early in the experiment, and two with performance later in
      the experiment. This outcome suggests dynamic changes occur in the recruitment of
      neural resources even within the initial period of exposure to an unfamiliar
      natural language.

PMID- 25058058
TI  - Involuntary switching into the native language induced by electrocortical
      stimulation of the superior temporal gyrus: a multimodal mapping study.
AB  - We describe involuntary language switching from L2 to L1 evoked by electro
      stimulation in the superior temporal gyrus in a 30-year-old right-handed Serbian
      (L1) speaker who was also a late Italian learner (L2). The patient underwent
      awake brain surgery. Stimulation of other portions of the exposed cortex did not
      cause language switching as did not stimulation of the left inferior frontal
      gyrus, where we evoked a speech arrest. Stimulation effects on language switching
      were selective, namely, interfered with counting behaviour but not with object
      naming. The coordinates of the positive site were combined with functional and
      fibre tracking (DTI) data. Results showed that the language switching site
      belonged to a significant fMRI cluster in the left superior temporal
      gyrus/supramarginal gyrus found activated for both L1 and L2, and for both the
      patient and controls, and did not overlap with the inferior fronto-occipital
      fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the superior
      longitudinal fasciculus (SLF). This area, also known as Stp, has a role in
      phonological processing. Language switching phenomenon we observed can be partly
      explained by transient dysfunction of the feed-forward control mechanism
      hypothesized by the DIVA (Directions Into Velocities of Articulators) model
      (Golfinopoulos, E., Tourville, J. A., & Guenther, F. H. (2010). The integration
      of large-scale neural network modeling and functional brain imaging in speech
      motor control.

PMID- 25058059
TI  - In vivo comparison of radiation exposure of dual-energy CT versus low-dose CT
      versus standard CT for imaging urinary calculi.
AB  - PURPOSE: Dual-energy computed tomography (DECT) is an emerging imaging modality
      with the unique capability of determining urinary stone composition. This study
      compares radiation exposure of DECT, standard single-energy CT (SECT), and low
      dose renal stone protocol single-energy CT (LDSECT) for the evaluation of
      nephrolithiasis in a single in vivo patient cohort. MATERIALS AND METHODS:
      Following institutional review board (IRB) approval, we retrospectively reviewed
      200 consecutive DECT examinations performed on patients with suspected
      urolithiasis over a 6-month period. Of these, 35 patients had undergone
      examination with our LDSECT protocol, and 30 patients had undergone examination
      of the abdomen and pelvis with our SECT imaging protocol within 2 years of the
      DECT examination. The CT dose index volume (CTDIvol) was used to compare
      radiation exposure between scans. Image quality was objectively evaluated by
      comparing image noise. Statistical evaluation was performed using a Student's t
      test. RESULTS: DECT performed at 80/140 kVp and 100/140 kVp did not produce a
      significant difference in radiation exposure compared with LDSECT (p=0.09 and
      0.18, respectively). DECT performed at 80/140 kVp and 100/140 kVp produced an
      average 40% and 31%, respectively, reduction in radiation exposure compared with
      SECT (p<0.001). For patients imaged with the 100/140 kVp protocol, average values
      for images noise were higher in the LDSECT images compared with DECT images
      (p<0.001) and there was no significant difference in image noise between DECT and
      SECT images in the same patient (p=0.88). Patients imaged with the 80/140 kVp
      protocol had equivocal image noise compared with LDSECT images (p=0.44), however,
      DECT images had greater noise compared with SECT images in the same patient
      (p<0.001). Of the 75 patients included in the study, stone material was available
      for 16; DECT analysis correctly predicted stone composition in 15/16 patients
      (93%). CONCLUSION: DECT provides knowledge of stone composition in addition to
      the anatomic information provided by LDSECT/SECT without increasing patient
      radiation exposure and with minimal impact on image noise.

PMID- 25058063
TI  - Dido, queen of Carthage: Leonard Limosin.

PMID- 25058060
TI  - Acyl chain length of phosphatidylserine is correlated with plant lifespan.
AB  - Plant lifespan is affected by factors with genetic and environmental bases. The
      laws governing these two factors and how they affect plant lifespan are unclear.
      Here we show that the acyl chain length (ACL) of phosphatidylserine (PS) is
      correlated with plant lifespan. Among the detected eight head-group classes of
      membrane lipids with lipidomics based on triple quadrupole tandem mass
      spectrometry, the ACL of PS showed high diversity, in contrast to the ACLs of the
      other seven classes, which were highly conserved over all stages of development
      in all plant species and organs and under all conditions that we studied. Further
      investigation found that acyl chains of PS lengthened during development,
      senescence, and under environmental stresses and that increasing length was
      accelerated by promoted- senescence. The acyl chains of PS were limited to a
      certain carbon number and ceased to increase in length when plants were close to
      death. These findings suggest that the ACL of PS can count plant lifespan and
      could be a molecular scale ruler for measuring plant development and senescence. 

PMID- 25058064
TI  - Virtual physician visits venture into mainstream use.

PMID- 25058065
TI  - Economist: It's time for tough choices on US health costs.

PMID- 25058066
TI  - FDA approves first celecoxib generics.

PMID- 25058079
TI  - Liberating data to transform health care: New York's open data experience.

PMID- 25058080
TI  - A piece of my mind. The case for social medicine.

PMID- 25058081
TI  - Autologous hematopoietic stem cell therapy in severe systemic sclerosis: ready
      for clinical practice?

PMID- 25058082
TI  - Breast cancer screening: should tomosynthesis replace digital mammography?

PMID- 25058084
TI  - Breast cancer screening using tomosynthesis in combination with digital
      mammography.
AB  - IMPORTANCE: Mammography plays a key role in early breast cancer detection. Single
      institution studies have shown that adding tomosynthesis to mammography increases
      cancer detection and reduces false-positive results. OBJECTIVE: To determine if
      mammography combined with tomosynthesis is associated with better performance of
      breast screening programs in the United States. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective analysis of screening performance metrics from 13
      academic and nonacademic breast centers using mixed models adjusting for site as
      a random effect. EXPOSURES: Period 1: digital mammography screening examinations
      1 year before tomosynthesis implementation (start dates ranged from March 2010 to
      October 2011 through the date of tomosynthesis implementation); period 2: digital
      mammography plus tomosynthesis examinations from initiation of tomosynthesis
      screening (March 2011 to October 2012) through December 31, 2012. MAIN OUTCOMES
      AND MEASURES: Recall rate for additional imaging, cancer detection rate, and
      positive predictive values for recall and for biopsy. RESULTS: A total of 454,850
      examinations (n=281,187 digital mammography; n=173,663 digital mammography +
      tomosynthesis) were evaluated. With digital mammography, 29,726 patients were
      recalled and 5056 biopsies resulted in cancer diagnosis in 1207 patients (n=815
      invasive; n=392 in situ). With digital mammography + tomosynthesis, 15,541
      patients were recalled and 3285 biopsies resulted in cancer diagnosis in 950
      patients (n=707 invasive; n=243 in situ). Model-adjusted rates per 1000 screens
      were as follows: for recall rate, 107 (95% CI, 89-124) with digital mammography
      vs 91 (95% CI, 73-108) with digital mammography + tomosynthesis; difference, -16
      (95% CI, -18 to -14; P < .001); for biopsies, 18.1 (95% CI, 15.4-20.8) with
      digital mammography vs 19.3 (95% CI, 16.6-22.1) with digital mammography +
      tomosynthesis; difference, 1.3 (95% CI, 0.4-2.1; P = .004); for cancer detection,
      4.2 (95% CI, 3.8-4.7) with digital mammography vs 5.4 (95% CI, 4.9-6.0) with
      digital mammography + tomosynthesis; difference, 1.2 (95% CI, 0.8-1.6; P < .001);
      and for invasive cancer detection, 2.9 (95% CI, 2.5-3.2) with digital mammography
      vs 4.1 (95% CI, 3.7-4.5) with digital mammography + tomosynthesis; difference,
      1.2 (95% CI, 0.8-1.6; P < .001). The in situ cancer detection rate was 1.4 (95%
      CI, 1.2-1.6) per 1000 screens with both methods. Adding tomosynthesis was
      associated with an increase in the positive predictive value for recall from 4.3%
      to 6.4% (difference, 2.1%; 95% CI, 1.7%-2.5%; P < .001) and for biopsy from 24.2%
      to 29.2% (difference, 5.0%; 95% CI, 3.0%-7.0%; P < .001). CONCLUSIONS AND
      RELEVANCE: Addition of tomosynthesis to digital mammography was associated with a
      decrease in recall rate and an increase in cancer detection rate. Further studies
      are needed to assess the relationship to clinical outcomes.

PMID- 25058083
TI  - Autologous hematopoietic stem cell transplantation vs intravenous pulse
      cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical
      trial.
AB  - IMPORTANCE: High-dose immunosuppressive therapy and autologous hematopoietic stem
      cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1
      and small phase 2 trials. OBJECTIVE: To compare efficacy and safety of HSCT vs 12
      successive monthly intravenous pulses of cyclophosphamide. DESIGN, SETTING, AND
      PARTICIPANTS: The Autologous Stem Cell Transplantation International Scleroderma
      (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel
      group, clinical trial conducted in 10 countries at 29 centers with access to a
      European Group for Blood and Marrow Transplantation-registered transplant
      facility. From March 2001 to October 2009, 156 patients with early diffuse
      cutaneous systemic sclerosis were recruited and followed up until October 31,
      2013. INTERVENTIONS: HSCT vs intravenous pulse cyclophosphamide. MAIN OUTCOMES
      AND MEASURES: The primary end point was event-free survival, defined as time from
      randomization until the occurrence of death or persistent major organ failure.
      RESULTS: A total of 156 patients were randomly assigned to receive HSCT (n = 79)
      or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events
      occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and
      31 in the control group (23 deaths and 8 irreversible organ failures). During the
      first year, there were more events in the HSCT group (13 events [16.5%],
      including 8 treatment-related deaths) than in the control group (8 events
      [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had
      occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control
      group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs
      20 events (26%) in the control group. Time-varying hazard ratios (modeled with
      treatment * time interaction) for event-free survival were 0.35 (95% CI, 0.16
      0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. CONCLUSIONS AND
      RELEVANCE: Among patients with early diffuse cutaneous systemic sclerosis, HSCT
      was associated with increased treatment-related mortality in the first year after
      treatment. However, HCST conferred a significant long-term event-free survival
      benefit. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN54371254.

PMID- 25058085
TI  - Anesthesia technique, mortality, and length of stay after hip fracture surgery.
AB  - IMPORTANCE: More than 300,000 hip fractures occur each year in the United States.
      Recent practice guidelines have advocated greater use of regional anesthesia for
      hip fracture surgery. OBJECTIVE: To test the association of regional (ie, spinal
      or epidural) anesthesia vs general anesthesia with 30-day mortality and hospital
      length of stay after hip fracture. DESIGN, SETTING, AND PATIENTS: We conducted a
      matched retrospective cohort study involving patients 50 years or older who were
      undergoing surgery for hip fracture at general acute care hospitals in New York
      State between July 1, 2004, and December 31, 2011. Our main analysis was a near
      far instrumental variable match that paired patients who lived at different
      distances from hospitals that specialized in regional or general anesthesia.
      Supplementary analyses included a within-hospital match that paired patients
      within the same hospital and an across-hospital match that paired patients at
      different hospitals. EXPOSURES: Spinal or epidural anesthesia; general
      anesthesia. MAIN OUTCOMES AND MEASURES: Thirty-day mortality and hospital length
      of stay. Because the distribution of length of stay had long tails, we
      characterized this outcome using the Huber M estimate with Huber weights, a
      robust estimator similar to a trimmed mean. RESULTS: Of 56,729 patients, 15,904
      (28%) received regional anesthesia and 40,825 (72%) received general anesthesia.
      Overall, 3032 patients (5.3%) died. The M estimate of the length of stay was 6.2
      days (95% CI, 6.2 to 6.2). The near-far matched analysis showed no significant
      difference in 30-day mortality by anesthesia type among the 21,514 patients
      included in this match: 583 of 10,757 matched patients (5.4%) who lived near a
      regional anesthesia-specialized hospital died vs 629 of 10,757 matched patients
      (5.8%) who lived near a general anesthesia-specialized hospital (instrumental
      variable estimate of risk difference, -1.1%; 95% CI, -2.8 to 0.5; P = .20).
      Supplementary analyses of within and across hospital patient matches yielded
      mortality findings to be similar to the main analysis. In the near-far match,
      regional anesthesia was associated with a 0.6-day shorter length of stay than
      general anesthesia (95% CI, -0.8 to -0.4, P < .001). Supplementary analyses also
      showed regional anesthesia to be associated with shorter length of stay, although
      the observed association was smaller in magnitude than in the main analysis.
      CONCLUSIONS AND RELEVANCE: Among adults in acute care hospitals in New York State
      undergoing hip repair, the use of regional anesthesia compared with general
      anesthesia was not associated with lower 30-day mortality but was associated with
      a modestly shorter length of stay. These findings do not support a mortality
      benefit for regional anesthesia in this setting.

PMID- 25058086
TI  - Levothyroxine prescription: not as simple as it seems.

PMID- 25058087
TI  - Topical and systemic antimicrobial therapy for venous leg ulcers.
AB  - CLINICAL QUESTION: Is treatment with topical or systemic antimicrobial agents
      associated with better venous leg ulcer healing compared with usual care
      (dressings and bandages without antimicrobials) or an alternative topical or
      systemic antimicrobial agent? BOTTOM LINE: Available evidence, from underpowered
      pooled data, neither supports nor refutes an association of systemic antibiotic
      therapy with improved venous leg ulcer healing. Among topical antimicrobials,
      cadexomer iodine may be associated with better healing compared with usual care.

PMID- 25058088
TI  - Diagnostic challenges of hepatitis C.

PMID- 25058089
TI  - Influence of chronic kidney disease on warfarin therapy for atrial fibrillation.

PMID- 25058090
TI  - Influence of chronic kidney disease on warfarin therapy for atrial fibrillation.

PMID- 25058091
TI  - Influence of chronic kidney disease on warfarin therapy for atrial fibrillation-
      reply.

PMID- 25058092
TI  - Therapies for venous thromboembolism.

PMID- 25058093
TI  - Therapies for venous thromboembolism--reply.

PMID- 25058094
TI  - Legal and ethical challenges in brain death.

PMID- 25058095
TI  - Legal and ethical challenges in brain death--reply.

PMID- 25058098
TI  - The alleged presence of bile salts in blood.

PMID- 25058099
TI  - Interrelation of bile pigment and hemoglobin.

PMID- 25058100
TI  - Operative management of displaced acetabular fractures: an institutional
      experience with a midterm follow-up.
AB  - BACKGROUND: Operative management is considered to be the treatment of choice in
      acetabular fractures as this is the unique way of achieving precise anatomical
      reduction, stable internal fixation, and early mobilization of joint. With this
      background in mind we undertook a prospective study with an aim to assess the
      outcome of surgery in displaced acetabular fractures at our general orthopedic
      centre as a first experience. MATERIAL AND METHODS: This study was conducted on
      59 patients (45 Males, 14 Females ) with mean age of 38.35 years (range 18-60
      years) with displaced acetabular fractures who were admitted consecutively at our
      centre from May 2008 through November 2011. Nine patients (7 Male, 2 Female) were
      lost during follow up. The average follow up was 3.5 years (range 2-5 years).
      Prophylaxis for deep venous thrombosis and heterotopic ossification was used
      routinely in all patients. RESULTS: Clinical evaluation was based on modified
      Merle-d'Aubigne and Postel scoring system. Radiological evaluation was done
      according to criteria developed by Matta. It was graded as excellent in 16% hips,
      good in 54% hips, fair in 20% hips and poor in 10% hips. Good to excellent
      results were achieved in 42 cases (70%). The complications included were implant
      backout, postoperative dislocation, iatrogenic nerve palsy, superficial wound
      infection, intraoperative bleeding and osteoarthritis. There is a positive
      relationship between quality of reduction and functional outcome. In our series,
      radiographic congruity (75%) correlated well with the function (70%).
      CONCLUSIONS: 1. We conclude that operative treatment is a safe and effective
      method of managing displaced acetabular fractures even in general orthopedic
      centres. 2. Time spent on a thorough study of the radiographs/CT scan for a
      proper preoperative plan is worthwhile and helps to outline an appropriate
      surgical approach and avoid complications.

PMID- 25058101
TI  - Total hip arthroplasty using cementless avantage cup in patients with risk of hip
      prosthesis instability.
AB  - BACKGROUND: The aim of the study was to assess total hip arthroplasty procedures
      using the cementless Avantage cup in women with additional risk factors for
      postoperative hip instability. MATERIAL AND METHODS: A total of 280 cementless
      Avantage and Avantage Reload cups were implanted in 260 women aged between 29 and
      79 years (60.9 years on average) in the years 2004-2010. In 217 women, there was
      at least one additional risk factor for prosthesis dislocation. The survival of
      the cup was assessed by using the necessity of cup replacement as an endpoint of
      the study. The statistical analyses used the Fisher test to assess the difference
      in the necessity of revision surgery between the Avantage and Avantage Reload
      cups, and the Kaplan Meier method was used to evaluate the effective functioning
      time of the prosthesis. Additionally, tests were conducted on the surface layer
      of 2 not used and 4 removed cups. RESULTS: 239 patients (259 arthroplasties) were
      subjected to the final examination. The follow-up period ranged from 2.7 to 9.7
      years, 7.0 years on average. None of the patients demonstrated postoperative
      prosthesis instability. Aseptic loosening was observed in 19 cups in 18 women
      (7.3%). Intra-prosthetic dislocation occurred 4 times, and in two cases it was
      combined with loosening of the cup. Revision surgery was required more often in
      patients with the Avantage cup (9.5%, 17 out of 179) in comparison to the
      Avantage Reload (2.5%, 2 out of 80). However, the observed differences did not
      reach the level of statistical significance. The cumulative survival rate of the
      Avantage cup was 0.94 at 5 years and 0.86 at 8 years. CONCLUSIONS: 1. Avantage
      cups reduce the risk of postoperative hip instability. 2. Patients with
      cementless Avantage cups should be closely monitored for signs of aseptic
      loosening.

PMID- 25058102
TI  - Outcomes of treatment of periprosthetic femoral fractures after total hip
      replacement - experience of department of orthopedics and traumatology, medical
      university of Warsaw.
AB  - BACKGROUND: As more and more hip replacement procedures are being performed, the
      incidence of periprosthetic femoral fractures is also growing. The aim of the
      study was to assess the outcomes of periprosthetic fracture treatment with the
      use of the functional Harris Hip Score (HHS). It compares the outcomes of
      periprosthetic fracture treatment and prefracture treatment results obtained
      during follow-up outpatient consultations. MATERIAL AND METHODS: The study
      involved 65 patients divided into the following four groups, depending on the
      type of the primary procedure: patients with periprosthetic femoral fractures
      after hip hemiarthroplasty; patients after cemented total hip replacement;
      patients after cementless arthroplasty; and patients after revision hip
      arthroplasty. The types of fractures were classified according to the Vancouver
      scale. RESULTS: The HHS questionnaires showed a deterioration of treatment
      outcomes in all patients from the four groups as compared with the outcomes
      obtained prior to the fracture. The most pronounced decrease in functional
      outcomes was observed in the group of patients after hemiarthroplasty and
      revision hip replacement. CONCLUSIONS: 1. The outcomes of periprosthetic fracture
      treatment, assessed with the HHS, are worse than the results obtained prior to
      the fracture. 2. Good results of periprosthetic fracture treatment were obtained
      only in patients with Vancouver Type B1 fractures. 3. The presence of co
      morbidities in elderly patients contributes to a poorer final result of
      periprosthetic fracture treatment.

PMID- 25058103
TI  - Errors in Treatment of Fractures of Distal Femur by LISS Method (Less Invasive
      Stabilization System) - Single-centre Experience.
AB  - BACKGROUND: LISS, the newest surgical method, makes it possible to completely
      regain knee function after knee fractures. We share our experience of the most
      frequently occurring errors during LISS-based treatment and ways of avoiding
      them. MATERIAL AND METHODS: Our sample consisted of patients treated with the
      LISS method between 2007 and 2012 in the Department of Orthopedics and
      Traumatology of the 4th Military Hospital in Wroclaw, Poland. We analysed the
      patients' radiographic records. RESULTS: We analysed follow-up radiographs of 28
      patients with fractures of the distal femur. We identified the following seven
      errors in reduction and fixation of fractures of the distal femur occurring
      during treatment using the LISS method: 1. Valgus or varus fracture fixation. 2.
      Malrotation of the fracture fragments. 3. Fixation in malrotation in the sagittal
      plane. 4. Non-axial placement of the LISS plate in the sagittal plane. 5. The use
      of K wires not recommended in the LISS method. 6. Screws penetrating into the
      joint. 7. Drilling holes for unicortical screws. CONCLUSIONS: 1. The most common
      errors in the treatment of fractures of the distal femur by LISS method relate to
      inadequate reduction of the fracture. 2. Intraoperative fluoroscopy should be
      used at all stages of the surgical procedure. 3. The surgical technique
      recommended by the creators of the LISS method must be strictly followed.

PMID- 25058104
TI  - The outcomes of cementless total ankle arthroplasty - pilot study.
AB  - BACKGROUND: Since new generation ankle endoprostheses came into common use, total
      ankle arthroplasty has become an alternative to arthrodesis in the treatment of
      advanced osteoarthritis. The aim of paper was present preliminary results of
      cementless total ankle arthroplasty in patients with osteoarthritis. MATERIAL AND
      METHODS: In 2012-2014, 12 cementless total arthroplasties of the ankle joint with
      a Mobility implant were conducted at the Department of Orthopaedics and
      Traumatology of the Central Clinical Hospital of the Ministry of Interior in
      Warsaw. The patients were 7 women and 5 men aged 27-72 years. Nine of the
      patients had the arthroplasty procedure due to severe post-traumatic degenerative
      changes while 3 patients had haemophilic arthropathy. Clinical assessment was
      based on the AOFAS scale and the VAS pain scale. The patients were followed up
      for at least 6 months. RESULTS: All patients improved considerably. After
      surgery, the AOFAS score improved by 43.0 (+/- 7.5) points against baseline while
      the VAS score improved by 5.2 (+/- 0.8) points. Imaging studies revealed an
      anatomical position of the endoprosthesis in all patients and no evidence of
      implant loosening. CONCLUSIONS: 1. Cementless total ankle arthroplasty currently
      seems to be an optimal solution in the treatment of osteo arthritis of the ankle
      joint. 2. Correct qualification for surgery is a prerequisite for successful
      treatment.

PMID- 25058105
TI  - Chronic recurrent multifocal osteomyelitis (CRMO) in children - single-centre
      clinical observations and experience.
AB  - BACKGROUND: CRMO is characterized by chronic bone pain of recurrent nature. The
      onset is usually at the beginning of the second decade of life. Bony lesions may
      be visible on radiographs, although sometimes a CT or MRI scan is necessary to
      visualise them. The aim of study was analyse symptoms, diagnostic difficulties
      and results of accessory investigations in patients suffering from CRMO. MATERIAL
      AND METHODS: Medical records of 42 patients with CRMO were analysed to assess:
      age at onset of the disease, symptoms reported, location of lesions and
      abnormalities in laboratory and imaging studies. RESULTS: The medical records of
      42 children, including 16 boys (38%) and 26 girls (62%), were analysed. The
      median age at onset was 10.5 years. The first symptom was bone pain in 34
      patients (81%), with the remaining 8 (19%) presenting with widened bone contour
      in the absence of pain. Initially, only 5 (12%) subjects had multiple foci,
      whereas the vast majority (88%) presented with a single lesion. During
      exacerbations, osteocalcin levels were significantly elevated, increasing to a
      mean of 34 ng/ml (max. 68, min.14.6) against a reference upper limit of 13.7
      ng/ml. Diagnostic difficulties and complications were found in 18 children.
      CONCLUSIONS: 1. Familiarity with CRMO in orthopaedic clinical practice is
      indispensable in differential diagnosis with other bone diseases, including those
      suggestive of malignancy. 2. Correctly diagnosed CRMO is managed conservatively
      as a treatment of choice.

PMID- 25058106
TI  - Evaluation of the effectiveness of platelet rich plasma in treatment of chronic
      pes anserinus pain syndrome.
AB  - BACKGROUND: Enthesopathy-associated pain does not only occur in athletes but also
      in persons of average daily activity levels. Repetitive microtrauma within the
      pes anserinus may lead to chronic inflammation and later result in development of
      degenerative changes in this region. It is commonly believed that this condition
      is caused by chronic bursitis of the pes anserinus. However, imaging studies have
      confirmed that as the underlying cause of complaints only in a small percentage
      of cases. MATERIAL AND METHODS: Between 2011 and 2012, a total of 33 patients
      with chronic pain in the pes anserinus were treated with platelet rich plasma at
      the Department of Orthopaedics, Military Institute of Medicine. All patients
      received 10 mL of autologous platelet rich plasma into the painful region. The
      effectiveness of platelet rich plasma was evaluated by comparing pre-treatment
      results and those obtained at 3 and 6 months following the therapy. Pain
      intensity was evaluated before and after treatment using a VAS scale and the
      modified Likert scale. RESULTS: A total of 28 patients (84.8% of the study
      participants) demon strated total or near-total pain relief within 6 months
      following treatment. CONCLUSIONS: 1. Pes anserinus pain syndrome is a relatively
      com mon condition in overweight and obese women over 50 years of age. 2. Our
      study demonstrated that a greater intensity of degenerative changes of the knee
      joint was ac companied by more severe pain in the pes anserinus area. 3. Platelet
      rich plasma is an effective treatment for pes anserinus pain. It produces pain
      relief and thus significantly improves the quality of life. 4. The response to
      platelet-derived growth factors was poorer in advanced degenerative knee joint
      disease. 5. Our treatment is safe; plasma administered to patients was obtained
      from their own peripheral blood and did not constitute a source of infection with
      viral hepatitis or HIV.

PMID- 25058107
TI  - The effect of land versus aquatic exercise program on bone mineral density and
      physical function in postmenopausal women with osteoporosis: a randomized
      controlled trial.
AB  - BACKGROUND: Osteoporosis is a multifactorial progressive skeletal disorder
      characterized by reduced bone mass. Exercise is widely recommended to reduce
      osteoporosis, falls and related fragility fractures. The purpose of this study
      was to investigate the effects of land exercise (LE) and aquatic exercise (AE) on
      physical function and bone mineral density (BMD). MATERIAL AND METHODS: Fifty
      eight postmenopausal women, aged 50-70 years, diagnosed with osteoporosis
      according to BMD measures, enrolled in this study. The subjects were randomly
      assigned to either the intervention group (LE group) or the control group (AE
      group). Physical function and BMD were assessed in all subjects in both groups
      before and after 10 months of intervention. Muscle strength, flexibility,
      balance, gait time and pain were measured to assess physical function. Bone
      mineral density at the lumbar spine was measured by dual energy X-ray
      absorptiometry (DEXA). RESULTS: There were no significant differences between the
      two groups in the baseline anthropometric data. The two groups were similar with
      respect to age, weight, height, and body mass index (p>0.05). After the exercise
      program, muscle strength, flexibility, gait time, pain, and bone density
      (p<0.001) improved significantly with LE compared to AE. There was no significant
      difference between the two groups with regard to balance at the 10-month follow
      up. CONCLUSION: Significant improvements in physical function and BMD suggest
      that LE is a possible alternative for postmenopausal women with OP.

PMID- 25058108
TI  - Primary bone lymphoma - experience of oncological orthopaedics department in
      Brzozow.
AB  - BACKGROUND: Primary bone lymphomas are very rare. The diagnosis is based on a
      histopathological examination and imaging studies where other disease foci should
      be excluded. The lymphomas are most often found in the axial skeleton, pelvis,
      femur and humerus. The tumour causes extensive lytic bone destruction with soft
      tissue infiltration. Surgical treatment is currently not used routinely. The aim
      of this study was to present five clinical cases and their most characteristic
      imaging features. MATERIAL AND METHODS: Over the last three years, 1327 patients
      with bone tumours have been hospitalized in the Oncological Orthopaedics
      Department in Brzozow, and most of these tumours (1184) were metastatic cancers.
      A total of 57 primary malignant bone tumours were diagnosed, of which five
      fulfilled the diagnostic criteria of primary bone lymphomas. Patient age and
      tumour sites varied. All the tumours were large, infiltrated soft tissues and
      caused osteolysis. No periosteal reactions or sequesters were observed. Two
      patients were treated surgically by radical resection and implantation of a
      prosthesis. The indication for surgery was tumour location enabling R0 resection.
      All patients received chemotherapy and radiotherapy. They have been followed up
      at the haematological and orthopaedic clinics. There is currently no evidence of
      generalized disease. RESULTS: The most characteristic feature of bone lymphomas
      is extensive osteolysis with soft tissue infiltration. The absence of false
      capsules helps distinguish lymphomas from sarcomas. No bone sequesters or
      osteosclerotic lesions described in the literature were observed in imaging
      examinations at our centre. Discussion. Diagnosis of a primary bone lymphoma is
      difficult as the tumour often resembles metastatic lesions. Secondary bone
      involvement is particularly difficult to differentiate from multifocal lymphoma.
      The Coley criteria are useful in diagnosis. If radical resection is possible,
      surgical treatment significantly improves prognosis. Radiotherapy has been
      associated with frequent recurrences of generalized disease and it is postulated
      that it should only be employed in palliative patients. CONCLUSIONS: 1. Primary
      bone lymphomas are rare tumours. 2. Imaging studies characteristically show
      extensive lytic bone destruction with soft tissue infiltration. 3. No sclerotic
      lesions or periosteal reactions were observed. 4. Surgical treatment should be
      performed when radical tumour resection is possible.

PMID- 25058109
TI  - The results of treatment of prostate cancer bone metastases after CyberKnife
      radiosurgery.
AB  - BACKGROUND: Bony metastases from prostate cancer are often associated with severe
      pain. Standard palliative radiotherapy does not provide full analgesic effect in
      most patients. CyberKnife radiosurgery allows for the precise treatment of small
      lesions, such as prostate cancer metastases, located in bones or near critical
      organs. object. Pilot study of the effectiveness of CyberKnife radiosurgery in
      the treatment of patients with bony oligometastases from prostate cancer.
      MATERIAL AND METHODS: CyberKnife radiosurgery was used in 48 cases of prostate
      cancer bone metastases (32 patients). Patients were treated with fraction doses
      of 6 to 15 Gy, delivered in 1-3 fractions, to a total dose of 6 to 45 Gy. PSA
      before the treatment varied from 0.01 to 387 ng/ml (mean 28.67; median 3.12).
      Lesions were located in the spine (31), pelvis (8), ribs (5) and cranium (4).
      Statistical analysis was performed for 12-months of follow-up using hierarchical
      linear modeling. RESULTS: PSA concentration decreased to 0.0-22.4 ng/ml (mean
      5.8; median 4.4) during the first month of follow-up. Linear correlations were
      found between total dose delivered and PSA concentration and pain relief. At the
      end of the follow-up period, an analgesic effect was observed, with complete pain
      relief in 28 patients and partial in 16. CONCLUSION: CyberKnife radiosurgery may
      be an effective method for the local treatment of patients with prostate cancer
      bone oligometastases, leading to a reduction of pain, reduced PSA concentration
      and a high rate of locoregional control.

PMID- 25058110
TI  - Characteristics of selected parameters of body posture in patients with hip
      osteoarthritis.
AB  - BACKGROUND: Osteoarthritis is the most common disorder of the musculoskeletal
      system. A unilateral change in the hip joint changes the position of the pelvis
      and spine, and therefore the patient's body posture. Due to the uneven loading of
      the lower limbs asymmetry occurs in the trunk. Detailed dependencies of that have
      not been thorougly described in the available literature. The aim of the study
      was to characterize the posture parameters in patients with unilateral
      osteoarthritis of the hip. MATERIAL AND METHODS: The study population consisted
      of 40 patients with unilateral hip osteoarthritis. There were 21 women and 19 men
      in the group, aged 41-80 years. The mean patient age was 65.39+/-8.69, the mean
      body mass was 82.98 +/- 11.79 kg, the mean body height was 167.64 +/- 8.59, and
      the mean Body Mass Index (BMI) was 29.6 +/- 4.36. RESULTS: Statistically
      significant differences were found on a number of parameters: lumbar inclination,
      thoraco-lumbar inclination and torso inclination were lower in patients with hip
      arthrosis, comparing to control group. Angle of thoracic kyphosis, depth of
      thoracic kyphosis, angle of lumbar lordosis, depth of lumbar lordosis were
      smaller in patients with hip arthrosis. Pelvic asymmetry in coronal plane was
      bigger in patients with hip arthrosis. CONCLUSION: Body posture in patients with
      unilateral osteoarthritis characterizes a decrease of lumbar lordosis and
      thoracic kyphosis while the whole body tilt forward. The asymmetry of the pelvis
      and trunk settings should be taken be taken into account during physical therapy
      of patients with coxarthrosis also during the post-operative postural re
      education process.

PMID- 25058111
TI  - Dopaminergic modulation of striatal networks in health and Parkinson's disease.
AB  - In the last couple of years, there have been significant advances in our
      understanding of how dopamine modulates striatal circuits underlying goal
      directed behaviors and how therapeutic interventions intended to normalize
      disordered dopaminergic signaling can go awry. This review summarizes some of the
      advances in this field with a translational focus on Parkinson's disease. 

PMID- 25058113
TI  - Enaminones via ruthenium-catalyzed coupling of thioamides and alpha-diazocarbonyl
      compounds.
AB  - Enaminones can be prepared via the Rh2(OAc)4-catalyzed coupling of alpha
      diazocarbonyl compounds with thioamides. However, rhodium is the most expensive
      and least abundant among the dominant precious metals used for catalysis.
      Furthermore, a very limited substrate scope is known for the intermolecular
      rhodium catalyzed coupling reaction. Therefore, there is a need to find a more
      economical catalyst substitute with a broad substrate scope. In this paper, we
      describe the use of Ru(II) catalysts for the synthesis of enaminones. The
      reaction can be performed efficiently with the Grubbs first-generation catalyst
      or [(Ph)3P]3RuCl2 in a sealed tube. Both catalysts are much less expensive than
      Rh2(OAc)4. Secondary and tertiary thioamides, when reacted with alpha
      diazodiesters, alpha-diazoketoesters, alpha-diazodiketones, and alpha
      diazomonoketones give enaminones. Primary thioamides give thiazole derivatives
      when reacted with alpha-diazomonoketones. However, with other diazo compounds,
      primary thioamides also give enaminones. All enaminones are obtained in good
      yields and with good diastereoselectivity. Accordingly, the method described in
      this paper is an efficient and economical alternative to the Rh2(OAc)4-catalyzed
      coupling process. 

PMID- 25058112
TI  - Behavioral state-dependent modulation of distinct interneuron subtypes and
      consequences for circuit function.
AB  - Multiple neuromodulators regulate neuronal response properties and synaptic
      connections in order to adjust circuit function. Inhibitory interneurons are a
      diverse group of cells that are differentially modulated depending on neuronal
      subtype and play key roles in regulating local circuit activity. Importantly, new
      tools to target specific subtypes are greatly improving our understanding of
      interneuron circuits and their modulation. Indeed, recent work has demonstrated
      that during different behavioral states interneuron activity changes in a subtype
      specific manner in both neocortex and hippocampus. Furthermore, in neocortex,
      modulation of specific interneuron microcircuits results in pyramidal cell
      disinhibition with important consequences for synaptic plasticity and animal
      behavior. Thus, neuromodulators tune the output of different interneuron subtypes
      to provide neural circuits with great flexibility. 

PMID- 25058114
TI  - Aureochrome 1 illuminated: structural changes of a transcription factor probed by
      molecular spectroscopy.
AB  - Aureochrome 1 from Vaucheria frigida is a recently identified blue-light receptor
      that acts as a transcription factor. The protein comprises a photosensitive light
      , oxygen- and voltage-sensitive (LOV) domain and a basic zipper (bZIP) domain
      that binds DNA rendering aureochrome 1 a prospective optogenetic tool. Here, we
      studied the photoreaction of full-length aureochrome 1 by molecular spectroscopy.
      The kinetics of the decay of the red-shifted triplet state and the blue-shifted
      signaling state were determined by time-resolved UV/Vis spectroscopy. It is shown
      that the presence of the bZIP domain further prolongs the lifetime of the LOV390
      signaling state in comparison to the isolated LOV domain whereas bound DNA does
      not influence the photocycle kinetics. The light-dark Fourier transform infrared
      (FTIR) difference spectrum shows the characteristic features of the flavin
      mononucleotide chromophore except that the S-H stretching vibration of cysteine
      254, which is involved in the formation of the thio-adduct state, is
      significantly shifted to lower frequencies compared to other LOV domains. The
      presence of the target DNA influences the light-induced FTIR difference spectrum
      of aureochrome 1. Vibrational bands that can be assigned to arginine and lysine
      side chains as well to the phosphate backbone, indicate crucial changes in
      interactions between transcription factor and DNA. 

PMID- 25058115
TI  - Primary blast-induced traumatic brain injury in rats leads to increased prion
      protein in plasma: a potential biomarker for blast-induced traumatic brain
      injury.
AB  - Traumatic brain injury (TBI) is deemed the "signature injury" of recent military
      conflicts in Afghanistan and Iraq, largely because of increased blast exposure.
      Injuries to the brain can often be misdiagnosed, leading to further complications
      in the future. Therefore, the use of protein biomarkers for the screening and
      diagnosis of TBI is urgently needed. In the present study, we have investigated
      the plasma levels of soluble cellular prion protein (PrPC) as a novel biomarker
      for the diagnosis of primary blast-induced TBI (bTBI). We hypothesize that the
      primary blast wave can disrupt the brain and dislodge extracellular localized
      PrPC, leading to a rise in concentration within the systemic circulation. Adult
      male Sprague-Dawley rats were exposed to single pulse shockwave overpressures of
      varying intensities (15-30 psi or 103.4-206.8 kPa] using an advanced blast
      simulator. Blood plasma was collected 24 h after insult, and PrPC concentration
      was determined with a modified commercial enzyme-linked immunosorbent assay
      (ELISA) specific for PrPC. We provide the first report that mean PrPC
      concentration in primary blast exposed rats (3.97 ng/mL +/- 0.13 SE) is
      significantly increased compared with controls (2.46 ng/mL +/- 0.14 SE; two
      tailed test p < 0.0001). Furthermore, we report a mild positive rank correlation
      between PrPC concentration and increasing blast intensity (psi) reflecting a
      plateaued response at higher pressure magnitudes, which may have implications for
      all military service members exposed to blast events. In conclusion, it appears
      that plasma levels of PrPC may be a novel biomarker for the detection of primary
      bTBI.

PMID- 25058117
TI  - Spontaneous rupture of the uterus during the 1st trimester of pregnancy.

PMID- 25058118
TI  - Prevalence of cleft lip and cleft palate in rural north-central guatemala.
AB  - OBJECTIVE: To estimate the number of new cases of cleft lip and cleft palate in
      the department (state) of Alta Verapaz, Guatemala, in 2012. DESIGN: Cross
      sectional survey of midwives from communities identified through a two-stage
      cluster-sampling process. Midwives were asked how many babies they had delivered
      in the past year and how many of those newborns had various types of birth
      defects, as illustrated in pictures. SETTING: Indigenous Mayan communities in
      rural north-central Guatemala. PARTICIPANTS: Midwives (n = 129) who had delivered
      babies in the previous year. MAIN OUTCOME MEASURE: Reports of babies born with
      cleft lip and cleft palate. RESULTS: A 1-year prevalence rate of 18.9 per 10,000
      for cleft lip and 4.7 per 10,000 for cleft palate was estimated for Alta Verapaz.
      None of the cases of cleft lip also had cleft palate. CONCLUSION: The indigenous
      communities in north-central Guatemala might have a relatively high cleft lip
      prevalence rate compared with the global average.

PMID- 25058116
TI  - A highly abundant bacteriophage discovered in the unknown sequences of human
      faecal metagenomes.
AB  - Metagenomics, or sequencing of the genetic material from a complete microbial
      community, is a promising tool to discover novel microbes and viruses. Viral
      metagenomes typically contain many unknown sequences. Here we describe the
      discovery of a previously unidentified bacteriophage present in the majority of
      published human faecal metagenomes, which we refer to as crAssphage. Its ~97 kbp
      genome is six times more abundant in publicly available metagenomes than all
      other known phages together; it comprises up to 90% and 22% of all reads in virus
      like particle (VLP)-derived metagenomes and total community metagenomes,
      respectively; and it totals 1.68% of all human faecal metagenomic sequencing
      reads in the public databases. The majority of crAssphage-encoded proteins match
      no known sequences in the database, which is why it was not detected before.
      Using a new co-occurrence profiling approach, we predict a Bacteroides host for
      this phage, consistent with Bacteroides-related protein homologues and a unique
      carbohydrate-binding domain encoded in the phage genome.

PMID- 25058119
TI  - Operative and Immediate Postoperative Outcomes of Using a Latham-Type
      Dentomaxillary Appliance in Patients With Unilateral Complete Cleft Lip and
      Palate.
AB  - OBJECTIVE: The objective of this study is to examine the operative and immediate
      postoperative effects of the use of a dentomaxillary appliance (DMA). DESIGN:
      Retrospective chart review of 40 treated patients with unilateral complete cleft
      lip and palate who had a comprehensive set of pre-, peri-, and postoperative
      records. SETTING: Boston Children's Hospital. PATIENTS: Forty treated patients
      with unilateral complete cleft lip and palate. INTERVENTIONS: Use of DMA. MAIN
      OUTCOME MEASURES: Outcome variables of interest included cleft lip width
      reduction following use of DMA and odds of having primary gingivoperiostetoplasty
      (GPP). RESULTS: The study sample included 40 subjects (31 boys and 9 girls). The
      average age at the time of DMA insertion was 11 weeks. The average width of the
      alveolar cleft prior to DMA insertion was 10.77 mm. The mean cleft width
      reduction was 8.66 mm. Each 1-mm increase in pre-DMA cleft width was associated
      with a 0.631-mm reduction in cleft width (P < .001). Thirty-three patients
      (82.5%) had a GPP procedure. Each 1-mm increase in post-DMA width was associated
      with a lower odds of having a GPP (odds ratio = 0.32, 95% confidence interval =
      0.14-0.77, P = .01). CONCLUSIONS: Post-DMA width was the significant factor
      associated with the performance of GPP. The use of DMA is associated with a
      significant reduction in the width of the cleft, and outcomes are predictable
      without any major adverse events or complications.

PMID- 25058120
TI  - Starting a Family: The Experience of Parents With Cleft Lip and/or Palate.
AB  - BACKGROUND: One of the key challenges facing young adults with cleft lip and/or
      palate is making decisions about starting a family, because there is an increased
      likelihood of their own child being diagnosed with cleft lip and/or palate.
      Should this occur, a second key challenge is how to deal with their child's
      diagnosis and subsequent treatment. OBJECTIVE: To explore the views, experiences
      and possible support needs of this unique group of parents in order to inform the
      services provided by nonspecialist Health Professionals, cleft teams, and genetic
      counselors. DESIGN: Individual telephone interviews eliciting qualitative data.
      RESULTS: Qualitative thematic analysis identified five themes. Accessing accurate
      information and appropriate support around heritability presented a significant
      challenge. Parents described feelings of responsibility and distress at their
      child's diagnosis, as well as a number of factors that had helped or hindered
      their adjustment. Parents also described ways in which their own experiences had
      impacted their parenting style and how becoming a parent had changed the way they
      felt about their own cleft. CONCLUSIONS: Young adults' understanding of what it
      means to grow up with cleft lip and/or palate may impact their decision to start
      a family and their experiences of having children. Possible methods of supporting
      prospective parents through this potentially difficult stage will be discussed.

PMID- 25058121
TI  - Perceptions of team members working in cleft services in the United kingdom: a
      pilot study.
AB  - BACKGROUND: Cleft care provision in the United Kingdom has been centralized over
      the past 15 years to improve outcomes for children born with cleft lip and
      palate. However, to date, there have been no investigations to examine how well
      these multidisciplinary teams are performing. METHODS: In this pilot study, a
      cross-sectional questionnaire surveyed members of all health care specialties
      working to provide cleft care in 11 services across the United Kingdom. Team
      members were asked to complete the Team Work Assessment (TWA) to investigate
      perceptions of team working in cleft services. The TWA comprises 55 items
      measuring seven constructs: team foundation, function, performance and skills,
      team climate and atmosphere, team leadership, and team identity; individual
      constructs were also aggregated to provide an overall TWA score. Items were
      measured using five-point Likert-type scales and were converted into percentage
      agreement for analysis. RESULTS: Responses were received from members of every
      cleft team. Ninety-nine of 138 cleft team questionnaires (71.7%) were returned
      and analyzed. The median (interquartile range) percentage of maximum possible
      score across teams was 75.5% (70.8, 88.2) for the sum of all items. Team
      performance and team identity were viewed most positively, with 82.0% (75.0,
      88.2) and 88.4% (82.2, 91.4), respectively. Team foundation and leadership were
      viewed least positively with 79.0% (72.6, 84.6) and 76.6% (70.6, 85.4),
      respectively. CONCLUSIONS: Cleft team members perceive that their teams work
      well, but there are variations in response according to construct.

PMID- 25058122
TI  - Occlusal Classification in Relation to Original Cleft Width in Patients With
      Unilateral Cleft Lip and Palate.
AB  - OBJECTIVE: To determine a correlation between the width of the cleft palate
      measured at the time of lip adhesion, definitive lip repair, and palatoplasty and
      the subsequent occlusal classification of patients born with unilateral cleft lip
      and palate. DESIGN: Retrospective, observational study. SETTING: Referral, urban,
      children's hospital Participants : Dental models and records of 270 patients were
      analyzed. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Angle occlusion
      classification. RESULTS: The mean age at which occlusal classification was
      determined was 11 +/- 0.3 years. Of the children studies, 84 were diagnosed with
      Class I or II occlusion, 67 were diagnosed with Class III occlusion, and 119 were
      lost to follow up or transferred care. Mean cleft widths were significantly
      larger in subjects with Class III occlusion for all measures at time of lip
      adhesion and definitive lip repair (P < .02). At time of palatoplasty, cleft
      widths were significantly greater at the alveolus (P = .025) but not at the
      midportion of the hard palate (P = .35) or posterior hard palate (P = .10).
      CONCLUSION: Cleft widths from the lip through to the posterior hard palate are
      generally greater in children who are diagnosed with Class III occlusion later in
      life. Notably, the alveolar cleft width is significantly greater at each time
      point for patients who went on to develop Class III occlusion. There were no
      significant differences in cleft widths between patients diagnosed later with
      Class I and Class II occlusions.

PMID- 25058123
TI  - Bilateral Hypodontia in Adolescents With Pierre Robin Sequence.
AB  - OBJECTIVE: To describe the frequency of hypodontia and left-right symmetry of
      hypodontia in the permanent dentition of children with Pierre Robin sequence
      (PRS). PATIENTS AND METHOD: The sample consisted of 78 children born with PRS
      between 1980 and 2006 and referred to the Oslo Cleft Lip and Palate Team (OCLPT).
      Data were collected retrospectively from the archives of the OCLPT. Panoramic
      radiographs were evaluated to document hypodontia; third molars were excluded.
      RESULTS: Of the 78 children with PRS, hypodontia was found in 33 (42%). Of the 33
      children with hypodontia, 27 (82%) showed hypodontia in the micrognathic lower
      arch, 24 (73%) were missing two or more permanent teeth, and 2 (6%) had
      oligodontia. The teeth most often missing were the mandibular second premolar
      (72%), followed by the maxillar second premolar (29%). Most cases of hypodontia
      21 (64%) occurred bilaterally. Bilateral hypodontia of the mandibular second
      premolar occurred in 27 (73%) of the patients. CONCLUSION: Hypodontia was found
      in 33 (42%) of the children with PRS, which is seven times higher than the
      prevalence among children without PRS (6%). Unlike in the general population,
      bilateral hypodontia was more common than unilateral hypodontia in the
      micrognathic mandible of children with PRS.

PMID- 25058124
TI  - Impact of introducing the line probe assay on time to treatment initiation of MDR
      TB in Delhi, India.
AB  - SETTING: National Institute of Tuberculosis and Respiratory Diseases (erstwhile
      Lala Ram Sarup Institute) in Delhi, India. OBJECTIVES: To evaluate before and
      after the introduction of the line Probe Assay (LPA) a) the overall time to MDR
      TB diagnosis and treatment initiation; b) the step-by-step time lapse at each
      stage of patient management; and c) the lost to follow-up rates. METHODS: A
      retrospective cohort analysis was done using data on MDR-TB patients diagnosed
      during 2009-2012 under Revised National Tuberculosis Control Programme at the
      institute. RESULTS: Following the introduction of the LPA in 2011, the overall
      median time from identification of patients suspected for MDR-TB to the
      initiation of treatment was reduced from 157 days (IQR 127-200) to 38 days (IQR
      30-79). This reduction was attributed mainly to a lower diagnosis time at the
      laboratory. Lost to follow-up rates were also significantly reduced after
      introduction of the LPA (12% versus 39% pre-PLA). CONCLUSION: Introduction of the
      LPA was associated with a major reduction in the delay between identification of
      patients suspected for MDR-TB and initiation of treatment, attributed mainly to a
      reduction in diagnostic time in the laboratory.

PMID- 25058125
TI  - Clinical and microbiological characteristics of recurrent group B streptococcal
      infection among non-pregnant adults.
AB  - OBJECTIVE: This study aimed to investigate the clinical and microbiological
      features of recurrent group B streptococcal (GBS) diseases among non-pregnant
      adults. METHODS: All hospitalized non-pregnant adults who had culture-proven GBS
      infections between January 2008 and December 2010 were enrolled in this
      retrospective study. Bacterial isolates were examined for their serotypes,
      genotypes, and antimicrobial resistance. RESULTS: The recurrence rate of GBS
      infection in Taiwan was found to be 9.3%. Of the 70 recurrent episodes in 32
      patients, infections of the urinary tract (U) were diagnosed clinically in 55.7%,
      infections of the soft tissue (S) in 31.4%, and infections of the bloodstream (B)
      in 12.9%. The initial/recurrent episodes in 25 patients were mainly U/U (40.6%),
      followed by S/S (18.8%) and B/B (6.2%). The serotypes/serogroups identified were
      serotypes V (34.3%), Ib (22.9%), VI (17.1%), III (12.9%), IV (7.1%), and Ia
      (5.7%). Recurrent strains showed less resistance to erythromycin or clindamycin
      than non-recurrent strains. Six distinct genotypes were identified in 12 serotype
      VI isolates derived from seven patients; five of these isolate pairs had
      identical genotypes. CONCLUSIONS: Recurrent GBS diseases were found to occur
      considerably more often than previously thought, mainly in adults with a high
      comorbid index. Relapse, not new acquisition, was found to be more common.

PMID- 25058126
TI  - An outbreak of food-borne salmonellosis linked to a bread takeaway shop in Ben
      Tre City, Vietnam.
AB  - OBJECTIVES: To identify the vehicle, source, and causative agent of a community
      wide food-borne outbreak of gastroenteritis. METHODS: We conducted a case-control
      study. Cases were city residents diagnosed with gastroenteritis and hospitalized
      in Ben Tre City from 22 to 25 May 2013; 41 cases were selected randomly from a
      list of hospitalized patients. Controls were age- and gender-matched healthy
      neighbours of cases. Participants were interviewed using a standard
      questionnaire. Samples from patients and food were tested at reference
      laboratories. We used conditional logistic regression to calculate matched odds
      ratios (mORs) for the association of gastroenteritis with food items consumed.
      RESULTS: Of the 41 cases enrolled in the study, 61% were males and the median age
      was 33 years; cases resided in 12 wards of the City. Of 13 food items consumed by
      the cases, only stuffed bread was significantly associated with gastroenteritis
      (mOR 21.3, 95% confidence interval 6.3-71.8). Among the 29 cases who ate stuffed
      bread, the median time to illness onset was 9h. Patient stool samples and bread
      samples were positive for Salmonella species. CONCLUSIONS: Stuffed bread was the
      likely vehicle of the outbreak. The laboratory testing capacity for serotypes of
      Salmonella should be strengthened in Vietnam. Food-handler training in basic food
      safety measures should be improved.

PMID- 25058127
TI  - The effect of maternal obesity on outcomes in patients undergoing tertiary or
      higher cesarean delivery.
AB  - OBJECTIVE: To estimate the association between maternal obesity and adverse
      outcomes in patients without placenta previa or accreta undergoing a tertiary or
      higher cesarean delivery. STUDY DESIGN: Retrospective cohort of patients cared
      for by a single MFM practice undergoing a tertiary or higher cesarean delivery
      from 2005 to 2013. Patients attempting vaginal delivery and patients with
      placenta accreta and/or placenta previa were excluded. We estimated the
      association of maternal obesity (prepregnancy BMI >= 30 kg/m(2)) and maternal
      outcomes. The primary outcome was a composite of severe maternal morbidity
      (uterine rupture, hysterectomy, blood transfusion, cystotomy requiring repair,
      bowel injury requiring repair, intensive care unit admission, thrombosis, re
      operation, or maternal death). RESULTS: Three hundred and forty four patients met
      inclusion criteria, 73 (21.2%) of whom were obese. The composite outcome was
      significantly higher in the obese group (6.8% versus 1.8%, p = 0.024, aOR 4.36,
      95% CI 1.21, 15.75). The incidence of several individual adverse outcomes were
      also increased in obese women, including blood transfusion (4.1% versus 0.7%, p =
      0.033, aOR 7.36, 95% CI 1.19, 45.34), wound separation or infection (20.5% versus
      5.9%, p < 0.001, aOR 4.05, 95% CI 1.75, 9.36) and 1-min Apgar score less than 7
      (6.8% versus 1.9%, p = 0.024, aOR 4.40, 95% CI 1.21, 15.94). CONCLUSIONS: In
      patients undergoing a tertiary or higher cesarean delivery without placenta
      previa or accreta, obesity increases the risk of adverse outcomes. Obese patients
      are at risk for blood transfusion, low 1-min Apgar scores and postoperative wound
      complications.

PMID- 25058128
TI  - Community turnover of wood-inhabiting fungi across hierarchical spatial scales.
AB  - For efficient use of conservation resources it is important to determine how
      species diversity changes across spatial scales. In many poorly known species
      groups little is known about at which spatial scales the conservation efforts
      should be focused. Here we examined how the community turnover of wood-inhabiting
      fungi is realised at three hierarchical levels, and how much of community
      variation is explained by variation in resource composition and spatial
      proximity. The hierarchical study design consisted of management type (fixed
      factor), forest site (random factor, nested within management type) and study
      plots (randomly placed plots within each study site). To examine how species
      richness varied across the three hierarchical scales, randomized species
      accumulation curves and additive partitioning of species richness were applied.
      To analyse variation in wood-inhabiting species and dead wood composition at each
      scale, linear and Permanova modelling approaches were used. Wood-inhabiting
      fungal communities were dominated by rare and infrequent species. The similarity
      of fungal communities was higher within sites and within management categories
      than among sites or between the two management categories, and it decreased with
      increasing distance among the sampling plots and with decreasing similarity of
      dead wood resources. However, only a small part of community variation could be
      explained by these factors. The species present in managed forests were in a
      large extent a subset of those species present in natural forests. Our results
      suggest that in particular the protection of rare species requires a large total
      area. As managed forests have only little additional value complementing the
      diversity of natural forests, the conservation of natural forests is the key to
      ecologically effective conservation. As the dissimilarity of fungal communities
      increases with distance, the conserved natural forest sites should be broadly
      distributed in space, yet the individual conserved areas should be large enough
      to ensure local persistence. 

PMID- 25058129
TI  - Science to practice: can intravoxel incoherent motion diffusion-weighted MR
      imaging be used to assess tumor response to antivascular drugs?
AB  - In the study by Joo et al (1), perfusion-sensitive parameters derived from
      diffusion-weighted (DW) magnetic resonance (MR) imaging using intravoxel
      incoherent motion (IVIM) analysis were significantly decreased 4 hours after
      administration of a vascular disrupting agent (VDA) (CKD-516), in keeping with
      drug-induced vascular collapse. A larger decrease in the perfusion-sensitive IVIM
      parameters was correlated with smaller tumor size increase 7 days after
      treatment.

PMID- 25058130
TI  - How should screening breast US be audited? The patient perspective.

PMID- 25058131
TI  - How should screening breast US be audited? The BI-RADS perspective.

PMID- 25058133
TI  - Moving beyond morphology: new insights into the characterization and management
      of cystic pancreatic lesions.
AB  - The frequency of detection of cystic pancreatic lesions with cross-sectional
      imaging, particularly with multidetector computed tomography, magnetic resonance
      (MR) imaging, and MR cholangiopancreatography, is increasing, and many of these
      cystic pancreatic lesions are being detected incidentally in asymptomatic
      patients. Because there is considerable overlap in the cross-sectional imaging
      findings of cystic pancreatic lesions, and because many of these lesions being
      detected are smaller than 3 cm in diameter and lack any specific cross-sectional
      imaging features, it has become difficult to make informed decisions about
      patient management when the precise diagnosis remains uncertain. This article
      presents the limitations of cross-sectional imaging in patients with cystic
      pancreatic lesions, details advances in knowledge of the genomic and epigenomic
      changes that lead to progression of carcinogenesis, outlines the current
      understanding of the natural history of mucinous cystic lesions, and includes the
      current use and future potential of novel tumor markers and molecular analysis to
      characterize cystic pancreatic lesions more precisely. The need to move beyond
      cross-sectional imaging morphology and toward the use of new techniques to
      diagnose these lesions accurately is emphasized. An algorithm that uses these
      techniques is proposed and will hopefully lead to improved patient management.

PMID- 25058137
TI  - Case 208: alkaptonuria.

PMID- 25058132
TI  - CT perfusion of the liver: principles and applications in oncology.
AB  - With the introduction of molecularly targeted chemotherapeutics, there is an
      increasing need for defining new response criteria for therapeutic success
      because use of morphologic imaging alone may not fully assess tumor response.
      Computed tomographic (CT) perfusion imaging of the liver provides functional
      information about the microcirculation of normal parenchyma and focal liver
      lesions and is a promising technique for assessing the efficacy of various
      anticancer treatments. CT perfusion also shows promising results for diagnosing
      primary or metastatic tumors, for predicting early response to anticancer
      treatments, and for monitoring tumor recurrence after therapy. Many of the
      limitations of early CT perfusion studies performed in the liver, such as limited
      coverage, motion artifacts, and high radiation dose of CT, are being addressed by
      recent technical advances. These include a wide area detector with or without
      volumetric spiral or shuttle modes, motion correction algorithms, and new CT
      reconstruction technologies such as iterative algorithms. Although several issues
      related to perfusion imaging-such as paucity of large multicenter trials, limited
      accessibility of perfusion software, and lack of standardization in methods
      remain unsolved, CT perfusion has now reached technical maturity, allowing for
      its use in assessing tumor vascularity in larger-scale prospective clinical
      trials. In this review, basic principles, current acquisition protocols, and
      pharmacokinetic models used for CT perfusion imaging of the liver are described.
      Various oncologic applications of CT perfusion of the liver are discussed and
      current challenges, as well as possible solutions, for CT perfusion are
      presented.

PMID- 25058138
TI  - Sequential or combined treatment? That is the question.

PMID- 25058139
TI  - Old dogs and plain radiographs.

PMID- 25058141
TI  - Cross-linked polymer nanofibers for hyperthermophilic enzyme immobilization:
      approaches to improve enzyme performance.
AB  - We report an enzyme immobilization method effective at elevated temperatures (up
      to 105  degrees C) and sufficiently robust for hyperthermophilic enzymes. Using a
      model hyperthermophilic enzyme, alpha-galactosidase from Thermotoga maritima,
      immobilization within chemically cross-linked poly(vinyl alcohol) (PVA)
      nanofibers to provide high specific surface area is achieved by (1)
      electrospinning a blend of a PVA and enzyme and (2) chemically cross-linking the
      polymer to entrap the enzyme within a water insoluble PVA fiber. The resulting
      enzyme-loaded nanofibers are water-insoluble at elevated temperatures, and enzyme
      leaching is not observed, indicating that the cross-linking effectively
      immobilizes the enzyme within the fibers. Upon immobilization, the enzyme retains
      its hyperthermophilic nature and shows improved thermal stability indicated by a
      5.5-fold increase in apparent half-life at 90  degrees C, but with a significant
      decrease in apparent activity. The loss in apparent activity is attributed to
      enzyme deactivation and mass transfer limitations. Improvements in the apparent
      activity can be achieved by incorporating a cryoprotectant during immobilization
      to prevent enzyme deactivation. For example, immobilization in the presence of
      trehalose improved the apparent activity by 10-fold. Minimizing the mat thickness
      to reduce interfiber diffusion was a simple and effective method to further
      improve the performance of the immobilized enzyme. 

PMID- 25058142
TI  - An efficient triazole-pyridine-bistetrazolate platform for highly luminescent
      lanthanide complexes.
AB  - Two new triazole-pyridine-bistetrazolate ligands were synthesized via a versatile
      procedure that allows for further derivatization; their corresponding homoleptic
      tris-ligand nona-coordinated lanthanide complexes are highly luminescent in the
      solid state and in a PVA polymeric matrix with measured values for the
      luminescence quantum yield of 70(7) and 98(9)% for Eu(III) and Tb(III),
      respectively. 

PMID- 25058143
TI  - Diffusion weighted MR and apparent diffusion coefficient measurement in
      classification and characterization of noncystic focal liver lesions: does a
      clinical role exist?
AB  - The objective of this study was to assess the clinical role of apparent diffusion
      coefficient (ADC) analysis in noncystic focal liver lesion (FLL)
      classification/characterization.Six hundred liver magnetic resonances with multi
      b (b = 50, 400, 800 s/mm) diffusion-weighted imaging (DwI) were retrospectively
      reviewed. Mean ADC was measured in 388 lesions (195 benign and 193 malignant)
      excluding internal necrotic areas. Cystic benign lesions were excluded from
      analysis. Sensitivity and specificity in distinguishing benign from malignant
      lesions were calculated. Analysis of variance was performed to detect differences
      among subgroups of solid lesions.Mean ADC of malignant lesions was 0.980 * 10
      mm/s, significantly (P < 0.05) lower than mean ADC of benign lesions (1.433 * 10
      mm/s). Applying an ADC cutoff of 1.066 * 10 mm/s, specificity and sensitivity for
      malignancy were respectively 86.6% and 73.6%. Of all lesions, >1/3 (39.5%)
      presented values lower than 1 * 10 mm/s, with 90.0% chance of malignancy. Above
      1.5 * 10 mm/s (about 20% of all lesions) chance of malignancy was 9.5%.DwI cannot
      assist in noncystic FLL characterization, but can help in FLL classification in
      about half the cases. 

PMID- 25058144
TI  - Askin tumor: CT and FDG-PET/CT imaging findings and follow-up.
AB  - The aim of the study was to describe the imaging findings of Askin tumors on
      computed tomography (CT) and fluorine 18 fluorodeoxyglucose-positron emission
      tomography (FDG-PET/CT).Seventeen cases of Askin tumors confirmed by
      histopathology were retrospectively analyzed in terms of CT (17 cases) and FDG
      PET/CT data (6 cases).Fifteen of the tumors were located in the chest wall and
      the other 2 were in the anterior middle mediastinum. Of the 15 chest wall cases,
      13 demonstrated irregular, heterogeneous soft tissue masses with cystic
      degeneration and necrosis, and 2 demonstrated homogeneous soft tissue masses on
      unenhanced CT scans. Two mediastinal tumors demonstrated the irregular,
      heterogeneous soft tissue masses. Calcifications were found in 2 tumors. The
      tumors demonstrated heterogeneously enhancement in 16 cases and homogeneous
      enhancement in 1 case on contrast-enhanced scans. FDG-PET/CT images revealed
      increased metabolic activity in all 6 cases undergone FDG-PET/CT scan, and the
      lesion SUVmax ranged from 4.0 to 18.6. At initial diagnosis, CT and FDG-PET/CT
      scans revealed rib destruction in 9 cases, pleural effusion in 9 cases, and lung
      metastasis in 1 case. At follow-up, 12 cases showed recurrence and/or metastases,
      4 cases showed improvement or remained stable, and 1 was lost to follow-up.In
      summary, CT and FDG-PET/CT images of Askin tumors showed heterogeneous soft
      tissue masses in the chest wall and the mediastinum, accompanied by rib
      destruction, pleural effusion, and increased FDG uptake. CT and FDG-PET/CT
      imaging play important roles in the diagnosis and follow-up of patients with
      Askin tumors. 

PMID- 25058145
TI  - Relevance of eosinophilia and hyper-IgE in immigrant children.
AB  - Immigrants from undeveloped countries are a growing problem in Europe. Spain has
      become a frequent destination for immigrants (20% of whom are children) because
      of its geographic location and its historic and cultural links with Africa and
      Latin America. Eosinophilia is frequent in adult immigrants, travelers and
      expatriates coming from tropical areas. However, there are few studies that focus
      on the incidence and causes of tropical eosinophilia and hyper-IgE in immigrant
      children.We evaluated, prospectively, the prevalence and causes of eosinophilia
      and hyper-immunoglobulin E (IgE) in 362 immigrant children coming from Sub
      Saharan Africa, Northern Africa and Latin America to Salamanca, Spain, between
      January 2007 and December 2011.Absolute eosinophilia and hyper-IgE were present
      in 22.9% and 56.8% of the analyzed children, respectively. The most frequent
      causes of absolute eosinophilia were filariasis (52.6%), strongyloidiasis (46.8%)
      and schistosomiasis (28.9%). Filariasis (41.9%), strongyloidiasis (29.6%) and
      schistosomiasis (22.2%) were the most frequent causes of increased levels of IgE.
      The area under the ROC curve showed similar values between eosinophil count and
      IgE levels in the diagnosis of helminthiasis (69% [95% confidence interval (CI)
      63%-74%] vs 67% [95% CI 60%-72%], P = 0.24). Eosinophilia and hyper-IgE have a
      high value as biomarkers of helminthiasis in children coming from tropical and
      subtropical areas. 

PMID- 25058146
TI  - Effect of salt intake and potassium supplementation on serum renalase levels in
      Chinese adults: a randomized trial.
AB  - Renalase, a recently discovered enzyme released by the kidneys, breaks down blood
      borne catecholamines and may thus regulate blood pressure (BP). Animal studies
      have suggested that high levels of dietary salt might reduce blood and kidney
      renalase levels. We conducted a randomized trial to assess the effects of altered
      salt and potassium intake on serum renalase levels and the relationship between
      serum renalase levels and BP in humans.Forty-two subjects (28-65 years of age)
      were selected from a rural community of northern China. All subjects were
      sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high
      salt diet for additional 7 days (18.0 g/day of NaCl), and a high-salt diet with
      potassium supplementation for final 7 days (18.0 g/day of NaCl + 4.5 g/day of
      KCl).Serum renalase levels were significantly higher than baseline levels during
      the low-salt diet intervention period. Renalase levels decreased with the change
      from the low-salt to high-salt diet, whereas dietary potassium prevented the
      decrease in serum renalase induced by the high-salt diet. There was a significant
      inverse correlation between the serum renalase level and 24-h urinary sodium
      excretion. No significant correlation was found between the renalase level and BP
      among the different dietary interventions.The present study indicates that
      variations in dietary salt intake and potassium supplementation affect the serum
      renalase concentration in Chinese subjects. 

PMID- 25058147
TI  - Crystal structure of the stress-inducible human heat shock protein 70 substrate
      binding domain in complex with peptide substrate.
AB  - The HSP70 family of molecular chaperones function to maintain protein quality
      control and homeostasis. The major stress-induced form, HSP70 (also called HSP72
      or HSPA1A) is considered an important anti-cancer drug target because it is
      constitutively overexpressed in a number of human cancers and promotes cancer
      cell survival. All HSP70 family members contain two functional domains: an N
      terminal nucleotide binding domain (NBD) and a C-terminal protein substrate
      binding domain (SBD); the latter is subdivided into SBDalpha and SBDbeta
      subdomains. The NBD and SBD structures of the bacterial ortholog, DnaK, have been
      characterized, but only the isolated NBD and SBDalpha segments of eukaryotic
      HSP70 proteins have been determined. Here we report the crystal structure of the
      substrate-bound human HSP70-SBD to 2 angstrom resolution. The overall fold of
      this SBD is similar to the corresponding domain in the substrate-bound DnaK
      structures, confirming a similar overall architecture of the orthologous
      bacterial and human HSP70 proteins. However, conformational differences are
      observed in the peptide-HSP70-SBD complex, particularly in the loop L(alpha,
      beta) that bridges SBDalpha to SBDbeta, and the loop L(L,1) that connects the SBD
      and NBD. The interaction between the SBDalpha and SBDbeta subdomains and the mode
      of substrate recognition is also different between DnaK and HSP70. This suggests
      that differences may exist in how different HSP70 proteins recognize their
      respective substrates. The high-resolution structure of the substrate-bound-HSP70
      SBD complex provides a molecular platform for the rational design of small
      molecule compounds that preferentially target this C-terminal domain, in order to
      modulate human HSP70 function.

PMID- 25058148
TI  - Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is
      due to preferential transduction of dendritic cells in vivo.
AB  - Gene transfer vectors such as lentiviral vectors offer versatile possibilities to
      express transgenic antigens for vaccination purposes. However, viral vaccines
      leading to broad transduction and transgene expression in vivo, are undesirable.
      Therefore, strategies capable of directing gene transfer only to professional
      antigen-presenting cells would increase the specific activity and safety of
      genetic vaccines. A lentiviral vector pseudotype specific for murine major
      histocompatibilty complex class II (LV-MHCII) was recently developed and the
      present study aims to characterize the in vivo biodistribution profile and
      immunization potential of this vector in mice. Whereas the systemic
      administration of a vector pseudotyped with a ubiquitously-interacting envelope
      led to prominent detection of vector copies in the liver of animals, the
      injection of an equivalent amount of LV-MHCII resulted in a more specific
      biodistribution of vector and transgene. Copies of LV-MHCII were found only in
      secondary lymphoid organs, essentially in CD11c+ dendritic cells expressing the
      transgene whereas B cells were not efficiently targeted in vivo, contrary to
      expectations based on in vitro testing. Upon a single injection of LV-MHCII,
      naive mice mounted specific effector CD4 and CD8 T cell responses against the
      intracelllular transgene product with the generation of Th1 cytokines,
      development of in vivo cytotoxic activity and establishment of T cell immune
      memory. The targeting of dendritic cells by recombinant viral vaccines must
      therefore be assessed in vivo but this strategy is feasible, effective for
      immunization and cross-presentation and constitutes a potentially safe
      alternative to limit off-target gene expression in gene-based vaccination
      strategies with integrative vectors. 

PMID- 25058149
TI  - Unsuspected leptospirosis is a cause of acute febrile illness in Nicaragua.
AB  - BACKGROUND: Epidemic severe leptospirosis was recognized in Nicaragua in 1995,
      but unrecognized epidemic and endemic disease remains unstudied.
      METHODOLOGY/PRINCIPAL FINDINGS: To determine the burden of and risk factors
      associated with symptomatic leptospirosis in Nicaragua, we prospectively studied
      patients presenting with fever at a large teaching hospital. Epidemiologic and
      clinical features were systematically recorded, and paired sera tested by IgM
      ELISA to identify patients with probable and possible acute leptospirosis.
      Microscopic Agglutination Test and PCR were used to confirm acute leptospirosis.
      Among 704 patients with paired sera tested by MAT, 44 had acute leptospirosis.
      Patients with acute leptospirosis were more likely to present during rainy months
      and to report rural residence and fresh water exposure. The sensitivity of
      clinical impression and acute-phase IgM detected by ELISA were poor.
      CONCLUSIONS/SIGNIFICANCE: Leptospirosis is a common (6.3%) but unrecognized cause
      of acute febrile illness in Nicaragua. Rapid point-of-care tests to support early
      diagnosis and treatment as well as tests to support population-based studies to
      delineate the epidemiology, incidence, and clinical spectrum of leptospirosis,
      both ideally pathogen-based, are needed.

PMID- 25058150
TI  - Making more matrix: enhancing the deposition of dermal-epidermal junction
      components in vitro and accelerating organotypic skin culture development, using
      macromolecular crowding.
AB  - Skin is one of the most accessible tissues for experimental biomedical sciences,
      and cultured skin cells represent one of the longest-running clinical
      applications of stem cell therapy. However, culture-generated skin mimetic
      multicellular structures are still limited in their application by the time taken
      to develop these constructs in vitro and by their incomplete differentiation. The
      development of a functional dermal-epidermal junction (DEJ) is one of the most
      sought after aspects of cultured skin, and one of the hardest to recreate in
      vitro. At the DEJ, dermal fibroblasts and epidermal keratinocytes interact to
      form an interlinked basement membrane of extracellular matrix (ECM), which forms
      as a concerted action of both keratinocytes and fibroblasts. Successful formation
      of this basement membrane is essential for take and stability of cultured skin
      autografts. We studied interactive matrix production by monocultures and
      cocultures of primary human keratinocytes and fibroblasts in an attempt to
      improve the efficiency of basement membrane production in culture using mixed
      macromolecular crowding (mMMC); resulting ECM were enriched with the deposition
      of collagens I, IV, fibronectin, and laminin 332 (laminin 5) and also in collagen
      VII, the anchoring fibril component. Our in vitro data point to fibroblasts,
      rather than keratinocytes, as the major cellular contributors of the DEJ. Not
      only did we find more collagen VII production and deposition by fibroblasts in
      comparison to keratinocytes, but also observed that decellularized fibroblast ECM
      stimulated the production and deposition of collagen VII by keratinocytes, over
      and above that of keratinocyte monocultures. In confrontation cultures,
      keratinocytes and fibroblasts showed spontaneous segregation and demarcation of
      cell boundaries by DEJ protein deposition. Finally, mMMC was used in a classical
      organotypic coculture protocol with keratinocytes seeded over fibroblast
      containing collagen gels. Applied during the submerged phase, mMMC was sufficient
      to accelerate the emergence of collagen VII along the de novo DEJ, together with
      stronger transglutaminase activity in the neoepidermis. Our findings corroborate
      the role of fibroblasts as important players in producing collagen VII and
      inducing collagen VII deposition in the DEJ, and that macromolecular crowding
      leads to organotypic epidermal differentiation in tissue culture in a
      significantly condensed time frame. 

PMID- 25058151
TI  - Association of severe thrombocytopenia and poor prognosis in pregnancies with
      aplastic anemia.
AB  - PURPOSE: We sought to estimate the risks of adverse obstetric outcomes and
      disease outcomes associated with severe thrombocytopenia in pregnant women with
      aplastic anemia (AA). METHODS: In a retrospective study, we compared
      demographics, clinical characteristics, laboratory results, and outcomes between
      severe thrombocytopenia (ST) and non-severe thrombocytopenia (non-ST) groups
      comprising pregnant women with AA. RESULTS: Of 61 AA patients, 43 (70%) were
      diagnosed as AA before pregnancy and 18 (30%) were AA during pregnancy. The ST
      group exhibited lower gestational age at nadir of platelet count (26.0 versus
      37.0 weeks, p<0.001) and at delivery (37.3 versus 39.1 weeks, p = 0.008), and a
      higher rate of bleeding gums (33.8 versus 7.7%, p = 0.015) than the non-ST group.
      In addition, the ST group exhibited more transfusions during pregnancy (72.7
      versus 15.4%, p<0.001) and postpartum period (45.0 versus 2.7%, p<0.001), and
      more bone marrow transplant after delivery (25.0 versus 0.0%, p<0.001) than the
      non-ST group. The ST group had a higher odds ratio of composite disease
      complications (OR, 9.63; 95% CI, 2.82-32.9; p<0.001) and composite obstetric
      complications (OR, 6.78; 95% CI, 2.11-21.8; p = 0.001) than the non-ST group.
      CONCLUSIONS: Severe thrombocytopenia is more associated with obstetric and
      disease complications than is non-severe thrombocytopenia in pregnant women with
      AA.

PMID- 25058153
TI  - Explorations of fungal biosynthesis of reduced polyketides - a personal
      viewpoint.
AB  - This viewpoint on biosynthesis of reduced polyketides in fungi traces evolution
      of the research area over more than 4 decades. It is a companion to the related
      articles by two personal and scientific friends with whom there has been free
      exchange of ideas for over 30 years. Beginning with very rudimentary knowledge
      about assembly of such natural products, developments using stable isotope
      labelling and subsequently identification of biosynthetic genes, led to
      understanding of the processive nature of polyketide formation. Recent expression
      and isolation of fungal iterative polyketide synthase enzymes has enabled more
      detailed exploration of the mechanisms of these fascinating molecular machines. 

PMID- 25058152
TI  - Functional EF-hands in neuronal calcium sensor GCAP2 determine its
      phosphorylation state and subcellular distribution in vivo, and are essential for
      photoreceptor cell integrity.
AB  - The neuronal calcium sensor proteins GCAPs (guanylate cyclase activating
      proteins) switch between Ca2+-free and Ca2+-bound conformational states and
      confer calcium sensitivity to guanylate cyclase at retinal photoreceptor cells.
      They play a fundamental role in light adaptation by coupling the rate of cGMP
      synthesis to the intracellular concentration of calcium. Mutations in GCAPs lead
      to blindness. The importance of functional EF-hands in GCAP1 for photoreceptor
      cell integrity has been well established. Mutations in GCAP1 that diminish its
      Ca2+ binding affinity lead to cell damage by causing unabated cGMP synthesis and
      accumulation of toxic levels of free cGMP and Ca2+. We here investigate the
      relevance of GCAP2 functional EF-hands for photoreceptor cell integrity. By
      characterizing transgenic mice expressing a mutant form of GCAP2 with all EF
      hands inactivated (EF-GCAP2), we show that GCAP2 locked in its Ca2+-free
      conformation leads to a rapid retinal degeneration that is not due to unabated
      cGMP synthesis. We unveil that when locked in its Ca2+-free conformation in vivo,
      GCAP2 is phosphorylated at Ser201 and results in phospho-dependent binding to the
      chaperone 14-3-3 and retention at the inner segment and proximal cell
      compartments. Accumulation of phosphorylated EF-GCAP2 at the inner segment
      results in severe toxicity. We show that in wildtype mice under physiological
      conditions, 50% of GCAP2 is phosphorylated correlating with the 50% of the
      protein being retained at the inner segment. Raising mice under constant light
      exposure, however, drastically increases the retention of GCAP2 in its Ca2+-free
      form at the inner segment. This study identifies a new mechanism governing GCAP2
      subcellular distribution in vivo, closely related to disease. It also identifies
      a pathway by which a sustained reduction in intracellular free Ca2+ could result
      in photoreceptor damage, relevant for light damage and for those genetic
      disorders resulting in "equivalent-light" scenarios. 

PMID- 25058154
TI  - Large-gap quantum spin Hall insulator in single layer bismuth monobromide Bi4Br4.
AB  - Quantum spin Hall (QSH) insulators have gapless topological edge states inside
      the bulk band gap, which can serve as dissipationless spin current channels. The
      major challenge currently is to find suitable materials for this topological
      state. Here, we predict a new large-gap QSH insulator with bulk direct band gap
      of ~ 0.18 eV, in single-layer Bi4Br4, which could be exfoliated from its three
      dimensional bulk material due to the weakly bonded layered structure. The band
      gap of single-layer Bi4Br4 is tunable via strain engineering, and the QSH phase
      is robust against external strain. Moreover, because this material consists of
      special one-dimensional molecular chain as its basic building block, the single
      layer Bi4Br4 could be torn to ribbons with clean and atomically sharp edges.
      These nanoribbons, which have single-Dirac-cone edge states crossing the bulk
      band gap, are ideal wires for dissipationless transport. Our work thus provides a
      new promising material for experimental studies and practical applications of the
      QSH effect.

PMID- 25058156
TI  - Expression of ghrelin and its receptor in rats after coronary artery ligation.
AB  - Ghrelin is a novel growth hormone-releasing peptide, which has been shown to
      exert beneficial effects on cardiac function and ventricular remodeling. The
      present study aimed to investigate the expression of ghrelin and the growth
      hormone (GH) secretagogue receptor 1a (GHSR-1a), and the association with cardiac
      remodeling in rats with myocardial infarction (MI). Twenty-four hours after
      ligation of the anterior descending artery (LAD), adult male Sprague-Dawley rats
      were randomized to 3 d, 7 d and 28 d group. Sham animals underwent thoracotomy
      and pericardiotomy, but not LAD ligation. Expression of both ghrelin and GHSR-1a
      was assessed by means of immunohistochemistry and real-time PCR. Plasma ghrelin
      levels were measured by ELISA kit. In addition, cardiac remodeling was assessed
      by echocardiographic and hemodynamic measurements. Plasma and cardiac expression
      of ghrelin decreased on days 3, 7 and 28 compared with the sham group (P<0.05).
      In contrast the GHSR-1a mRNA levels increased during the same days (P<0.05).
      Decreased positive immunoreaction for ghrelin and increased positive GHSR-1a were
      also observed in the infarcted heart. Interestingly, plasma ghrelin correlated
      negatively with left ventricular end-diastolic pressure (r=-0.59, P=0.002) and
      left ventricular end-diastolic dimension (r=-0.73, P<0.01). The ghrelin system
      may play an important role regulating cardiac remodeling after MI and present as
      a potential significant target for pharmacological modulation and treating
      cardiac remodeling.

PMID- 25058155
TI  - Quercetin inhibits intestinal iron absorption and ferroportin transporter
      expression in vivo and in vitro.
AB  - Balancing systemic iron levels within narrow limits is critical for maintaining
      human health. There are no known pathways to eliminate excess iron from the body
      and therefore iron homeostasis is maintained by modifying dietary absorption so
      that it matches daily obligatory losses. Several dietary factors can modify iron
      absorption. Polyphenols are plentiful in human diet and many compounds, including
      quercetin--the most abundant dietary polyphenol--are potent iron chelators. The
      aim of this study was to investigate the acute and longer-term effects of
      quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to
      quercetin increased apical iron uptake but decreased subsequent basolateral iron
      efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4
      carbonyl groups and methylation of the 3-hydroxyl group negated both the increase
      in apical uptake and the inhibition of basolateral iron release, suggesting that
      the acute effects of quercetin on iron transport were due to iron chelation. In
      longer-term studies, rats were administered quercetin by a single gavage and iron
      transporter expression measured 18 h later. Duodenal FPN expression was decreased
      in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed
      to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression
      of FPN by quercetin was not a transcriptional event but might be mediated by
      miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for
      the regulation of iron bioavailability by dietary polyphenols. Potentially, diets
      rich in polyphenols might be beneficial for patients groups at risk of iron
      loading by limiting the rate of intestinal iron absorption.

PMID- 25058157
TI  - Photon upconversion in core-shell nanoparticles.
AB  - Photon upconversion generally results from a series of successive electronic
      transitions within complex energy levels of lanthanide ions that are embedded in
      the lattice of a crystalline solid. In conventional lanthanide-doped upconversion
      nanoparticles, the dopant ions homogeneously distributed in the host lattice are
      readily accessible to surface quenchers and lose their excitation energy, giving
      rise to weak and susceptible emissions. Therefore, present studies on
      upconversion are mainly focused on core-shell nanoparticles comprising spatially
      confined dopant ions. By doping upconverting lanthanide ions in the interior of a
      core-shell nanoparticle, the upconversion emission can be substantially enhanced,
      and the optical integrity of the nanoparticles can be largely preserved.
      Optically active shells are also frequently employed to impart multiple
      functionalities to upconversion nanoparticles. Intriguingly, the core-shell
      design introduces the possibility of constructing novel upconversion
      nanoparticles by exploiting the energy exchange interactions across the core
      shell interface. In this tutorial review, we highlight recent advances in the
      development of upconversion core-shell nanoparticles, with particular emphasis on
      the emerging strategies for regulating the interplay of dopant interactions
      through core-shell nanostructural engineering that leads to unprecedented
      upconversion properties. The improved control over photon energy conversion will
      open up new opportunities for biological and energy applications. 

PMID- 25058158
TI  - Volumetric absorptive microsampling: a dried sample collection technique for
      quantitative bioanalysis.
AB  - Volumetric absorptive microsampling (VAMS) is a novel approach to obtaining a
      dried blood sample for quantitative bioanalysis that overcomes the area bias and
      homogeneity issues associated with conventional dried blood spot (DBS) sample
      when a subpunch is taken. The VAMS sampler absorbs a fixed volume of blood (~10
      MUL) in 2-4 s with less than 5% volume variation across the hematocrit range of
      20-70% with low tip-to-tip variability. There is no evidence of selective
      absorption by the tip of the plasma component over whole blood. Recommendations
      for best practice when collecting samples were developed based upon the results
      of tests examining a number of potential abuse scenarios. 

PMID- 25058160
TI  - Reduction in acute ecotoxicity of paper mill effluent by sequential application
      of xylanase and laccase.
AB  - In order to reduce the ecotoxicity of paper mill, four different enzymatic
      pretreatment strategies were investigated in comparison to conventional chemical
      based processes. In strategy I, xylanase-aided pretreatment of pulp was carried
      out, and in strategy II, xylanase and laccase-mediator systems were used
      sequentially. Moreover, to compare the efficiency of Bacillus stearothermophilus
      xylanase and Ceriporiopsis subvermispora laccase in the reduction of ecotoxicity
      and pollution, parallel strategies (III and IV) were implemented using commercial
      enzymes. Conventional C(D)E(OP)D(1)D(2) (C(D), Cl(2) with ClO2; EOP, H2O2
      extraction; D1 and D2, ClO2) and X/XLC(D)E(OP)D(1)D(2) (X, xylanase; L, laccase)
      sequences were employed with non-enzymatic and enzymatic strategies,
      respectively. Acute toxicity was determined by the extent of inhibition of
      bioluminescence of Vibrio fischeri with different dilutions of the effluent. Two
      fold increase was observed in EC50 values for strategy I compared to the control
      process. On the other hand, sequential application of commercial enzymes resulted
      in higher acute toxicity compared to lab enzymes. In comparison to the control
      process, strategy II was the most efficient and successfully reduced 60.1 and
      25.8% of biological oxygen demand (BOD) and color of effluents, respectively. We
      report for the first time the comparative analysis of the ecotoxicity of
      industrial effluents.

PMID- 25058161
TI  - The midbrain periaqueductal grey has no role in the generation of the respiratory
      motor pattern, but provides command function for the modulation of respiratory
      activity.
AB  - It has previously been shown that stimulation of cell-columns in the
      periaqueductal grey (PAG) triggers site-specific cardiorespiratory effects. These
      are believed to facilitate changes in behaviour through coordinated changes in
      autonomic outflow. Here, we investigated whether PAG-evoked respiratory commands
      can be studied in situ using the decerebrate perfused brainstem preparation.
      Phrenic, vagus and abdominal iliohypogastric nerves were recorded before and
      after microinjection of L-glutamate (30-50 nl, 10 mM) or isoguvacine (GABA
      receptor agonist, 30-50 nl, 10 mM) into the PAG. L-glutamate microinjection
      triggered a range of site-specific respiratory modulations (n = 17 preparations).
      Subsequent microinjection of isoguvacine into the same PAG sites had no effect on
      the baseline respiratory motor pattern or rhythm. We conclude that while the PAG
      has no function in respiratory pattern generation, PAG-evoked respiratory
      modulations can be evoked in situ in the absence of higher brain centres and
      while homeostatic parameters that may affect respiratory drive are held static.

PMID- 25058162
TI  - Alveolar mechanics studied by in vivo microscopy imaging through intact pleural
      space.
AB  - In six male anesthetized, tracheotomized, and mechanically ventilated rabbits we
      derived indications on alveolar mechanics from in vivo imaging, using a "pleural
      window" technique (pleural space intact) that allows unrestrained movement of the
      same subpleural alveoli (N=60) on increasing alveolar pressure from 4 to 8 cmH2O.
      Absolute compliance (C(abs), ratio of change in alveolar surface area to the
      change in alveolar pressure) was significantly lower in smaller compared to
      larger alveoli. Specific compliance, C(sp), obtained by normalizing C(abs) to
      alveolar surface area, was essentially independent of alveolar size. Both C(abs)
      and C(sp) were affected by large variability likely reflecting the complex
      matching between elastic and surface forces. We hypothesize that the relative
      constancy of C(sp) might contribute to reduce interregional differences in
      parenchymal and surface forces in the lung tissue by contributing to assure a
      uniform stretching in a model of mechanically inter-dependent alveoli.

PMID- 25058159
TI  - iRegulon: from a gene list to a gene regulatory network using large motif and
      track collections.
AB  - Identifying master regulators of biological processes and mapping their
      downstream gene networks are key challenges in systems biology. We developed a
      computational method, called iRegulon, to reverse-engineer the transcriptional
      regulatory network underlying a co-expressed gene set using cis-regulatory
      sequence analysis. iRegulon implements a genome-wide ranking-and-recovery
      approach to detect enriched transcription factor motifs and their optimal sets of
      direct targets. We increase the accuracy of network inference by using very large
      motif collections of up to ten thousand position weight matrices collected from
      various species, and linking these to candidate human TFs via a motif2TF
      procedure. We validate iRegulon on gene sets derived from ENCODE ChIP-seq data
      with increasing levels of noise, and we compare iRegulon with existing motif
      discovery methods. Next, we use iRegulon on more challenging types of gene lists,
      including microRNA target sets, protein-protein interaction networks, and genetic
      perturbation data. In particular, we over-activate p53 in breast cancer cells,
      followed by RNA-seq and ChIP-seq, and could identify an extensive up-regulated
      network controlled directly by p53. Similarly we map a repressive network with no
      indication of direct p53 regulation but rather an indirect effect via E2F and
      NFY. Finally, we generalize our computational framework to include regulatory
      tracks such as ChIP-seq data and show how motif and track discovery can be
      combined to map functional regulatory interactions among co-expressed genes.
      iRegulon is available as a Cytoscape plugin from http://iregulon.aertslab.org. 

PMID- 25058163
TI  - The CD27L and CTP1L endolysins targeting Clostridia contain a built-in trigger
      and release factor.
AB  - The bacteriophage PhiCD27 is capable of lysing Clostridium difficile, a
      pathogenic bacterium that is a major cause for nosocomial infection. A
      recombinant CD27L endolysin lyses C. difficile in vitro, and represents a
      promising alternative as a bactericide. To better understand the lysis mechanism,
      we have determined the crystal structure of an autoproteolytic fragment of the
      CD27L endolysin. The structure covers the C-terminal domain of the endolysin, and
      represents a novel fold that is identified in a number of lysins that target
      Clostridia bacteria. The structure indicates endolysin cleavage occurs at the
      stem of the linker connecting the catalytic domain with the C-terminal domain. We
      also solved the crystal structure of the C-terminal domain of a slow cleaving
      mutant of the CTP1L endolysin that targets C. tyrobutyricum. Two distinct
      dimerization modes are observed in the crystal structures for both endolysins,
      despite a sequence identity of only 22% between the domains. The dimers are
      validated to be present for the full length protein in solution by right angle
      light scattering, small angle X-ray scattering and cross-linking experiments
      using the cross-linking amino acid p-benzoyl-L-phenylalanine (pBpa). Mutagenesis
      on residues contributing to the dimer interfaces indicates that there is a link
      between the dimerization modes and the autocleavage mechanism. We show that for
      the CTP1L endolysin, there is a reduction in lysis efficiency that is
      proportional to the cleavage efficiency. We propose a model for endolysin
      triggering, where the extended dimer presents the inactive state, and a switch to
      the side-by-side dimer triggers the cleavage of the C-terminal domain. This leads
      to the release of the catalytic portion of the endolysin, enabling the efficient
      digestion of the bacterial cell wall. 

PMID- 25058164
TI  - Topical lidocaine for neuropathic pain in adults.
AB  - BACKGROUND: Lidocaine is a local anaesthetic that is sometimes used on the skin
      to treat neuropathic pain. OBJECTIVES: To assess the analgesic efficacy of
      topical lidocaine for chronic neuropathic pain in adults, and to assess the
      associated adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, and
      EMBASE from inception to 1 July 2014, together with the reference lists of
      retrieved papers and other reviews. We also searched ClinicalTrials.gov and the
      World Health Organization (WHO) International Clinical Trials Registry Platform
      (ICTRP) search portal to identify additional published or unpublished data.
      SELECTION CRITERIA: We included randomised, double-blind studies of at least two
      weeks' duration comparing any formulation of topical lidocaine with placebo or
      another active treatment in chronic neuropathic pain. Participants were adults
      aged 18 and over. We included only full journal publication articles. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted efficacy and
      adverse event data, and examined issues of study quality. We performed analysis
      using three tiers of evidence. First tier evidence derived from data meeting
      current best standards and subject to minimal risk of bias (outcome equivalent to
      substantial pain intensity reduction, intention-to-treat analysis without
      imputation for dropouts; at least 200 participants in the comparison, 8 to 12
      weeks' duration, parallel design); second tier evidence from data that failed to
      meet one or more of these criteria and that we considered at some risk of bias
      but with adequate numbers in the comparison; and third tier evidence from data
      involving small numbers of participants that we considered very likely to be
      biased or used outcomes of limited clinical utility, or both. MAIN RESULTS: We
      included 12 studies (508 participants) in comparisons with placebo or an active
      control. Six studies enrolled participants with moderate or severe postherpetic
      neuralgia, and the remaining studies enrolled different, or mixed, neuropathic
      pain conditions, including trigeminal neuralgia and postsurgical or post
      traumatic neuralgia. Four different formulations were used: 5% medicated patch,
      5% cream, 5% gel, and 8% spray. Most studies used a cross-over design, and two
      used a parallel-group design. Two studies used enriched enrolment with randomised
      withdrawal. Seven studies used multiple doses, with one to four-week treatment
      periods, and five used single applications. We judged all of the studies at high
      risk of bias because of small size or incomplete outcome assessment, or
      both.There was no first or second tier evidence, and no pooling of data was
      possible for efficacy outcomes. Only one multiple-dose study reported our primary
      outcome of participants with >= 50% or >= 30% pain intensity reduction. Three
      single-dose studies reported participants who were pain-free at a particular time
      point, or had a 2-point (of 10) reduction in pain intensity. The two enriched
      enrolment, randomised withdrawal studies reported time to loss of efficacy. In
      all but one study, third tier (very low quality) evidence indicated that
      lidocaine was better than placebo for some measure of pain relief. Pooling
      multiple-dose studies across conditions demonstrated no clear evidence of an
      effect of lidocaine on the incidence of adverse events or withdrawals, but there
      were few events and the withdrawal phase of enriched enrolment designs is not
      suitable to assess the true impact of adverse events (very low quality evidence).
      AUTHORS' CONCLUSIONS: This review found no evidence from good quality randomised
      controlled studies to support the use of topical lidocaine to treat neuropathic
      pain, although individual studies indicated that it was effective for relief of
      pain. Clinical experience also supports efficacy in some patients. Several large
      ongoing studies, of adequate duration, with clinically useful outcomes should
      provide more robust conclusions about both efficacy and harm.

PMID- 25058166
TI  - Engineering RNA-protein complexes with different shapes for imaging and
      therapeutic applications.
AB  - Molecular machines composed of RNA-protein (RNP) complexes may expand the fields
      of molecular robotics, nanomedicine, and synthetic biology. However, constructing
      and directly visualizing a functional RNP nanostructure to detect and control
      living cell function remains a challenge. Here we show that RNP nanostructures
      with modular functions can be designed and visualized at single-RNP resolution in
      real time. The RNP structural images collected in solution through high-speed
      atomic force microscopy showed that a single RNP interaction induces a
      conformational change in the RNA scaffold, which supports the nanostructure
      formation designed. The specific RNP interaction also improved RNA nanostructure
      stability in a serum-containing buffer. We developed and visualized functional
      RNPs (e.g., to detect human cancer cells or knockdown target genes) by attaching
      a protein or RNA module to the same RNA scaffold of an optimal size. The
      synthetic RNP architecture may provide alternative materials to detect and
      control functions in target mammalian cells.

PMID- 25058165
TI  - Characterization of postoperative changes in nasal airflow using a cadaveric
      computational fluid dynamics model: supporting the internal nasal valve.
AB  - IMPORTANCE: Collapse or compromise of the internal nasal valve (INV) results in
      symptomatic nasal obstruction; thus, various surgical maneuvers are designed to
      support the INV. OBJECTIVE: To determine the effect on nasal airflow after
      various surgical techniques focused at the level of the INV and lateral nasal
      sidewall. DESIGN AND SETTING: A fresh cadaver head was obtained and underwent
      suture and cartilage graft techniques directed at the level of the INV using an
      external approach. Preoperative and postoperative digital nasal models were
      created from the high-resolution, fine-cut, computed tomographic imaging after
      each intervention. Isolating the interventions to the level of the INV, we used
      computational fluid dynamic techniques to calculate nasal resistance, nasal
      airflow, and nasal airflow partitioning for each intervention. INTERVENTION:
      Suture and cartilage graft techniques. MAIN OUTCOMES AND MEASURES: Nasal airflow,
      nasal resistance, and partitioning of airflow. RESULTS: Using the soft-tissue
      elevation model as baseline, computational fluid dynamic analysis predicted that
      most of the suture and cartilage graft techniques directed toward the nasal valve
      improved nasal airflow and partitioning while reducing nasal resistance.
      Specifically, medial and modified flare suture techniques alone improved nasal
      airflow by 16.9% and 15.1%, respectively. The combination of spreader grafts and
      modified flare suture improved nasal airflow by 13.2%, whereas spreader grafts
      alone only improved airflow by 5.9%. The largest improvements in bilateral nasal
      resistance were achieved using the medial and modified flare sutures,
      outperforming the combination of spreader grafts and modified flare suture.
      CONCLUSIONS AND RELEVANCE: Techniques directed at supporting the INV have
      tremendous value in the treatment of nasal obstruction. The use of flare sutures
      alone can address dynamic valve collapse or upper lateral cartilage incompetence
      without gross disruption of the nasal architecture. Using computational fluid
      dynamic techniques, this study suggests that flare sutures alone may improve flow
      and reduce resistance when placed medially, surpassing spreader grafts alone or
      in combination with flare sutures. The longevity of these maneuvers can only be
      assessed in the clinical setting. Studies in additional specimens and clinical
      correlation in human subjects deserve further attention and investigation. LEVEL
      OF EVIDENCE: NA.

PMID- 25058167
TI  - Structure and growth of the leeward Kohala field system: an analysis with
      directed graphs.
AB  - This study illustrates how the theory of directed graphs can be used to
      investigate the structure and growth of the leeward Kohala field system, a
      traditional Hawaiian archaeological site that presents an unparalleled
      opportunity to investigate relative chronology. The relative chronological
      relationships of agricultural walls and trails in two detailed study areas are
      represented as directed graphs and then investigated using graph theoretic
      concepts including cycle, level, and connectedness. The structural properties of
      the directed graphs reveal structure in the field system at several spatial
      scales. A process of deduction yields a history of construction in each detailed
      study area that is different than the history produced by an earlier
      investigation. These results indicate that it is now possible to study the
      structure and growth of the entire field system remnant using computer software
      implementations of graph theoretic concepts applied to observations of
      agricultural wall and trail intersections made on aerial imagery and/or during
      fieldwork. A relative chronology of field system development with a resolution of
      one generation is a possible result. 

PMID- 25058169
TI  - Chemistry and photochemistry of 2,6-bis(2-hydroxybenzilidene)cyclohexanone. An
      example of a compound following the anthocyanins network of chemical reactions.
AB  - The kinetics and thermodynamics of the 2,6-bis(2-hydroxybenzilidene)cyclohexanone
      chemical reactions network was studied at different pH values using NMR, UV-vis,
      continuous irradiation, and flash photolysis. The chemical behavior of the system
      partially resembles anthocyanins and their analogue compounds. 2,6-Bis(2
      hydroxybenzilidene)cyclohexanone exhibits a slow color change from yellow to red
      styrylflavylium under extreme acidic conditions. The rate constant for this
      process (5 * 10(-5) s(-1)) is pH independent and controlled by the cis-trans
      isomerization barrier. However, the interesting feature is the appearance of the
      colorless compound, 7,8-dihydro-6H-chromeno[3,2-d]xanthene, isolated from
      solutions of acid to neutral range, characterized by (1)H NMR and single crystal
      X-ray diffraction. Light absorption by 2,6-bis(2-hydroxybenzilidene)cyclohexanone
      solutions immediately after preparation exclusively results in cis-isomer as
      photoproduct, which via hemiketal formation yields (i) red styrylflavylium by
      dehydration under extremely acidic solutions (pH < 1) and (ii) colorless 7,8
      dihydro-6H-chromeno[3,2-d]xanthene by cyclization in solutions of acid to neutral
      range. 

PMID- 25058168
TI  - Evaluation of (89)Zr-pertuzumab in Breast cancer xenografts.
AB  - Pertuzumab is a monoclonal antibody that binds to HER2 and is used in combination
      with another HER2-specific monoclonal antibody, trastuzumab, for the treatment of
      HER2+ metastatic breast cancer. Pertuzumab binds to an HER2 binding site distinct
      from that of trastuzumab, and its affinity is enhanced when trastuzumab is
      present. We aim to exploit this enhanced affinity of pertuzumab for its HER2
      binding epitope and adapt this antibody as a PET imaging agent by radiolabeling
      with (89)Zr to increase the sensitivity of HER2 detection in vivo. Here, we
      investigate the biodistribution of (89)Zr-pertuzumab in HER2-expressing BT-474
      and HER2-nonexpressing MDA-MB-231 xenografts to quantitatively assess HER2
      expression in vivo. In vitro cell binding studies were performed resulting in
      retained immunoreactivity and specificity for HER2-expressing cells. In vivo
      evaluation of (89)Zr-pertuzumab was conducted in severely combined
      immunodeficient mice, subcutaneously inoculated with BT-474 and MDA-MB-231 cells.
      (89)Zr-pertuzumab was systemically administered and imaged at 7 days
      postinjection (p.i.) followed by terminal biodistribution studies. Higher tumor
      uptake was observed in BT-474 compared to MDA-MB-231 xenografts with 47.5 +/-
      32.9 and 9.5 +/- 1.7% ID/g, respectively at 7 days p.i (P = 0.0009) and blocking
      studies with excess unlabeled pertuzumab showed a 5-fold decrease in BT-474 tumor
      uptake (P = 0.0006), confirming the in vivo specificity of this radiotracer.
      Importantly, we observed that the tumor accumulation of (89)Zr-pertuzumab was
      increased in the presence of unlabeled trastuzumab, at 173 +/- 74.5% ID/g (P =
      0.01). Biodistribution studies correlate with PET imaging quantification using
      max SUV (r = 0.98, P = 0.01). Collectively, these results illustrate that (89)Zr
      pertuzumab as a PET imaging agent may be beneficial for the quantitative and
      noninvasive assessment of HER2 expression in vivo especially for patients
      undergoing trastuzumab therapy. 

PMID- 25058170
TI  - Immunofluorescently labeling glutamic acid decarboxylase 65 coupled with confocal
      imaging for identifying GABAergic somata in the rat dentate gyrus-A comparison
      with labeling glutamic acid decarboxylase 67.
AB  - As gamma-aminobutyric acid (GABA) is synthesized by two isoforms of glutamic acid
      decarboxylase (GAD), namely, GAD65 and GAD67, immunohistochemically targeting
      either isoform of GAD is theoretically useful for identifying GABAergic cell
      bodies. In practice, targeting GAD67 remains to be a popular choice. However,
      identifying GABAergic cell bodies with GAD67 immunoreactivity in the hippocampal
      dentate gyrus, especially in the hilus, is not without pitfalls. In the present
      study, we compared the characteristics of GAD65 immunoreactivity to GAD67
      immunoreactivity in the rat dentate gyrus and examined perikaryal expression of
      GAD65 in four neurochemically prevalent subgroups of interneurons in the hilus.
      Experiments were done in normal adult Sprague-Dawley rats and GAD67-GFP knock-in
      mice. Horizontal hippocampal slices cut from the ventral portion of hippocampi
      were immunofluorescently stained and scanned using a confocal microscope.
      Immunoreactivity for both GAD67 and GAD65 was visible throughout the dentate
      gyrus. Perikaryal GAD67 immunoreactivity was denser but variable in terms of
      distribution pattern and intensity among cells whereas perikaryal GAD65
      immunoreactivity displayed similar distribution pattern and staining intensity.
      Among different layers of the dentate gyrus, GAD67 immunoreactivity was densest
      in the hilus despite GAD65 immunoreactivity being more intense in the granule
      cell layer. Co-localization experiments showed that GAD65, but not GAD67, was
      expressed in all hilar calretinin (CR)-, neuronal nitric oxide synthase (nNOS)-,
      parvalbumin (PV)- or somatostatin (SOM)-positive somata. Labeling CR, nNOS, PV,
      and SOM in sections obtained from GAD67-GFP knock-in mice revealed that a large
      portion of SOM-positive cells had weak GFP expression. In addition, double
      labeling of GAD65/GABA and GAD67/GABA showed that nearly all of GABA
      immunoreactive cells had perikaryal GAD65 expression whereas more than one-tenth
      of GABA-immunoreactive cells lacked perikaryal GAD67 immunoreactivity. Inhibition
      of axonal transport with colchicine dramatically improved perikaryal GAD65
      immunoreactivity in GABAergic cells without significant augmentation to be seen
      in granule cells. Double labeling GAD65 and GAD67 in the sections obtained from
      colchicine-pretreated animals confirmed that a portion of GAD65-immunoreactive
      cells had weak or even no GAD67 immunoreactivity. We conclude that for confocal
      imaging, immunofluorescently labeling GAD65 for identifying GABAergic somata in
      the hilus of the dentate gyrus has advantages over labeling GAD67 in terms of
      easier recognition of perikaryal labeling and more consistent expression in
      GABAergic somata. Inhibition of axonal transport with colchicine further improves
      perikaryal GAD65 labeling, making GABAergic cells more distinguishable. 

PMID- 25058171
TI  - Distribution of immunoreactive glutamine synthetase in the adult human and mouse
      brain. Qualitative and quantitative observations with special emphasis on extra
      astroglial protein localization.
AB  - Glutamine synthetase catalyzes the ATP-dependent condensation of ammonia and
      glutamate to form glutamine, thus playing a pivotal role in glutamate and
      glutamine homoeostasis. Despite a plethora of studies on this enzyme, knowledge
      about the regional and cellular distribution of this enzyme in human brain is
      still fragmentary. Therefore, we mapped fourteen post-mortem brains of
      psychically healthy individuals for the distribution of the glutamine synthetase
      immunoreactive protein. It was found that glutamine synthetase immunoreactivity
      is expressed in multiple gray and white matter astrocytes, but also in
      oligodendrocytes, ependymal cells and certain neurons. Since a possible extra
      astrocytic expression of glutamine synthetase is highly controversial, we paid
      special attention to its appearance in oligodendrocytes and neurons. By double
      immunolabeling of mouse brain slices and cultured mouse brain cells for glutamine
      synthetase and cell-type-specific markers we provide evidence that besides
      astrocytes subpopulations of oligodendrocytes, microglial cells and neurons
      express glutamine synthetase. Moreover, we show that glutamine synthetase
      immunopositive neurons are not randomly distributed throughout human and mouse
      brain, but represent a subpopulation of nitrergic (i.e. neuronal nitric oxide
      synthase expressing) neurons. Possible functional implications of an extra
      astrocytic localization of glutamine synthetase are discussed. 

PMID- 25058172
TI  - Plasma chemical and chemical functionalization of polystyrene colloidal crystals.
AB  - Self-assembling systems of colloidal spheres are widely used as templates for the
      structured deposition of metals and semiconductors. Multilayer samples of ordered
      polystyrene spheres are prepared by a flow induced process. The subsequent
      surface activation by a dielectric barrier discharge in oxygen is followed by the
      fabrication of protecting polysiloxane layers. Electrochemical deposition of
      copper is used to test the stability of the pre-treated colloidal crystal. The
      arrangement of the spheres is preserved during the deposition process, due to the
      polysiloxane layer. The results of the consecutive preparation steps are
      investigated concerning topographical and chemical changes by atomic force
      microscopy, scanning electron microscopy and X-ray photoelectron spectroscopy. 

PMID- 25058173
TI  - Predicting the bioconcentration of fragrance ingredients by rainbow trout using
      measured rates of in vitro intrinsic clearance.
AB  - Bioaccumulation in aquatic species is a critical end point in the regulatory
      assessment of chemicals. Few measured fish bioconcentration factors (BCFs) are
      available for fragrance ingredients. Thus, predictive models are often used to
      estimate their BCFs. Because biotransformation can reduce chemical accumulation
      in fish, models using QSAR-estimated biotransformation rates have been developed.
      Alternatively, biotransformation can be measured by in vitro methods. In this
      study, biotransformation rates for nine fragrance ingredients were measured using
      trout liver S9 fractions and used as inputs to a recently refined in vitro-in
      vivo extrapolation (IVIVE) model. BCFs predicted by the model were then compared
      to (i) in vivo BCFs, (ii) BCFs predicted using QSAR-derived biotransformation
      rates, (iii) BCFs predicted without biotransformation, and (iv) BCFs predicted by
      a well-known regression model. For fragrance ingredients with relatively low
      (<4.7) log K(OW) values, all models predicted BCFs below a bioaccumulation
      threshold of 1000. For chemicals with higher (4.7-5.8) log K(OW) values, the
      model incorporating measured in vitro biotransformation rates and assuming no
      correction for potential binding effects on hepatic clearance provided the most
      accurate predictions of measured BCFs. This study demonstrates the value of
      integrating measured biotransformation rates for prediction of chemical
      bioaccumulation in fish.

PMID- 25058174
TI  - Structure-property relationship of bifunctional MnO2 nanostructures: highly
      efficient, ultra-stable electrochemical water oxidation and oxygen reduction
      reaction catalysts identified in alkaline media.
AB  - Manganese oxides of various structures (alpha-, beta-, and delta-MnO2 and
      amorphous) were synthesized by facile methods. The electrocatalytic properties of
      these materials were systematically investigated for catalyzing both oxygen
      evolution reaction (OER) and oxygen reduction reaction (ORR) in alkaline media.
      Extensive characterization was correlated with the activity study by
      investigating the crystal structures (XRD, HRTEM), morphologies (SEM), porosities
      (BET), surfaces (XPS, O2-TPD/MS), and electrochemical properties (Tafel analysis,
      Koutechy-Levich plots, and constant-current electrolysis). These combined results
      show that the electrocatalytic activities are strongly dependent on the
      crystallographic structures, and follow an order of alpha-MnO2 > AMO > beta-MnO2
      > delta-MnO2. Both OER studies and ORR studies reveal similar structure
      determined activity trends in alkaline media. In the OER studies, alpha-MnO2
      displays an overpotential of 490 mV compared to 380 mV shown by an Ir/C catalyst
      in reaching 10 mA cm(-2). Meanwhile, alpha-MnO2 also exhibits stability for 3 h
      when supplying a constant current density of 5 mA cm(-2). This was further
      improved by adding Ni(2+) dopants (ca. 8 h). The superior OER activity was
      attributed to several factors, including abundant di-MU-oxo bridges existing in
      alpha-MnO2 as the protonation sites, analogous to the OEC in PS-II of the natural
      water oxidation system; the mixed valencies (AOS = 3.7); and the lowest charge
      transfer resistances (91.8 Omega, eta = 430 mV) as revealed from in situ
      electrochemical impedance spectroscopy (EIS). In the ORR studies, when reaching 3
      mA cm(-2), alpha-MnO2 shows 760 mV close to 860 mV for the best ORR catalyst (20%
      Pt/C). The outstanding ORR activity was due to the strongest O2 adsorption
      capability of alpha-MnO2 suggested by temperature-programmed desorption. As a
      result, this discovery of the structure-related electrocatalytic activities could
      provide guidance in the further development of easily prepared, scalable, and low
      cost catalysts based on metal oxides and their derivatives. 

PMID- 25058175
TI  - Novel insights into adrenal insufficiency in childhood.
AB  - Adrenal insufficiency (AI) is a rare disease in childhood and adolescence that
      results from disruption in the hypothalamic-pituitary-adrenal axis. Pediatricians
      should be familiar with this entity since acute adrenal crisis is a life
      threatening condition that requires immediate treatment. In the early stages of
      AI, the clinical manifestations may be subtle and non-specific; thus, they are
      frequently unrecognized. The main therapeutic approach in all forms of adrenal
      insufficiency is glucocorticoid replacement; the dose should be titrated
      appropriately to avoid under or overtreatment. Patient and family education is
      particularly important, to enable adjustment of dosage replacement therapy during
      stress and to prevent crisis. This article summarizes the current knowledge of AI
      and provides new insights on its management in children. 

PMID- 25058176
TI  - Renaissance of antibiotics against difficult infections: Focus on oritavancin and
      new ketolides and quinolones.
AB  - Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical
      development, with specific advantages over available molecules within their
      respective classes. The lipoglycopeptide oritavancin is bactericidal against
      MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus
      pneumoniae, and proved effective and safe for the treatment of acute bacterial
      skin and skin structure infection (ABSSSI) upon administration of a single 1200
      mg dose (two completed phase III trials). The ketolide solithromycin (two phase
      III studies recruiting for community-acquired pneumonia) shows a profile of
      activity similar to that of telithromycin, but in vitro data suggest a lower risk
      of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due
      to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and
      delafloxacin share the unique property of an improved activity in acidic
      environments (found in many infection sites). Finafloxacin (phase II completed;
      activity profile similar to that of ciprofloxacin) is evaluated for complicated
      urinary tract and Helicobacter pylori infections. The other quinolones (directed
      towards Gram-positive pathogens) show improved activity on MRSA and
      multiresistant S. pneumoniae compared to current molecules. They are in clinical
      evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and
      delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and
      nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).

PMID- 25058177
TI  - Epigenetic reprogramming in breast cancer: from new targets to new therapies.
AB  - Breast cancer is the most commonly diagnosed cancer and the second leading cause
      of cancer death among women in the United States. Recently, interest has grown in
      the role of epigenetics in breast cancer development and progression. Epigenetic
      changes such as DNA methylation, histone modifications, and abnormal expression
      of non-coding RNAs emerged as novel biomarkers in breast cancer diagnosis,
      therapy, and prevention. This review focuses on the most recent mechanistic
      findings underlying epigenetic changes in breast cancer development and their
      role as predictors of breast cancer risk. The rapid progress in our understanding
      of epigenetic findings in breast cancer has opened new avenues for potential
      therapeutic approaches via identification of epigenetic targets. We highlight the
      development of novel epigenetically targeted drugs, relevant clinical trials in
      breast cancer patients, and recent approaches combining epigenetic agents with
      chemotherapy and/or endocrine therapy that may incrementally improve long-term
      outcomes in appropriately selected breast cancer patients. Biomarkers of response
      are needed, however, to identify patient subsets that are most likely to benefit
      from epigenetic treatment strategies.

PMID- 25058178
TI  - Brucellosis as an emerging threat in developing economies: lessons from Nigeria.
AB  - Nigeria is the most populous country in Africa, has a large proportion of the
      world's poor livestock keepers, and is a hotspot for neglected zoonoses. A review
      of the 127 accessible publications on brucellosis in Nigeria reveals only scant
      and fragmented evidence on its spatial and temporal distribution in different
      epidemiological contexts. The few bacteriological studies conducted demonstrate
      the existence of Brucella abortus in cattle and sheep, but evidence for B.
      melitensis in small ruminants is dated and unclear. The bulk of the evidence
      consists of seroprevalence studies, but test standardization and validation are
      not always adequately described, and misinterpretations exist with regard to
      sensitivity and/or specificity and ability to identify the infecting Brucella
      species. Despite this, early studies suggest that although brucellosis was
      endemic in extensive nomadic systems, seroprevalence was low, and brucellosis was
      not perceived as a real burden; recent studies, however, may reflect a changing
      trend. Concerning human brucellosis, no studies have identified the Brucella
      species and most reports provide only serological evidence of contact with
      Brucella in the classical risk groups; some suggest brucellosis misdiagnoses as
      malaria or other febrile conditions. The investigation of a severe outbreak that
      occurred in the late 1970s describes the emergence of animal and human disease
      caused by the settling of previously nomadic populations during the Sahelian
      drought. There appears to be an increasing risk of re-emergence of brucellosis in
      sub-Saharan Africa, as a result of the co-existence of pastoralist movements and
      the increase of intensive management resulting from growing urbanization and food
      demand. Highly contagious zoonoses like brucellosis pose a threat with far
      reaching social and political consequences. 

PMID- 25058195
TI  - The interaction between anxiety and depressive symptoms on brachial artery
      reactivity in cardiac patients.
AB  - The association between anxiety, depression, and endothelial function (EF) was
      assessed in a sample of 295 cardiac outpatients (n=222 men; mean age=59).
      Patients were administered the Beck Depression Inventory-II and the State-Trait
      Anxiety Inventory, trait scale. EF was assessed through forearm hyperemic
      reactivity, a nuclear medicine variation of the flow-mediated dilatation
      technique, which calculates the rate of uptake ratio (RUR) between hyperaemic and
      non-hyperaemic arms. Neither effect of anxiety (F=1.40, p=.24) nor depression
      (F=2.66, p=.10) was found in a model predicting EF, however there was an
      interaction (F=4.11, p=.04). Higher anxiety and lower depressive symptoms were
      associated with superior RUR compared to lower anxiety and lower depressive
      symptoms. Anxiety had no influence on RUR in those patients with higher
      depressive symptoms, who generally displayed the lowest levels of RUR, i.e., poor
      function. It is speculative whether this potential protective role of anxiety may
      be guided by behavioral or physiological mechanisms. 

PMID- 25058196
TI  - Gender-specific genital and subjective sexual arousal to prepotent sexual
      features in heterosexual women and men.
AB  - Heterosexual women respond genitally to stimuli featuring both their preferred
      and nonpreferred genders, whereas men's genital responses are gender-specific,
      suggesting that gender cues are less relevant to women's sexual response.
      Instead, prepotent sexual features (exposed and sexually aroused genitals),
      ubiquitous in audiovisual sexual stimuli, may elicit automatic genital responses,
      thereby leading to a nonspecific sexual arousal pattern in women. To examine the
      role of stimulus potency in women's sexual response, we assessed heterosexual
      women's and men's genital and subjective sexual arousal to slideshows of
      prepotent stimuli (erect penises and aroused vulvas), non-prepotent stimuli
      (flaccid penises and female pubic triangles), and sexually neutral stimuli.
      Contrary to our hypotheses, both women and men demonstrated gender-specific
      genital and subjective sexual arousal, such that sexual arousal was greatest to
      prepotent male and female stimuli, respectively. This is the first study to
      demonstrate gender-specific genital responding in heterosexual women. 

PMID- 25058197
TI  - Regional anesthesia in pediatrics: marching forward.
AB  - PURPOSE OF REVIEW: This review highlights new data and current trends of well
      tolerated and effective paediatric regional anesthesia. Historically, the
      practice of paediatric regional anesthesia was based largely on information from
      adult studies, but recent literature contains information on paediatric specific
      risks and benefits of old and new techniques as well as the impact of new ideas
      and technologies. RECENT FINDINGS: Excellent pain relief with regional anesthesia
      is well demonstrated in children. Several databases of paediatric regional
      anesthesia (over 46,000 regional anesthetics) demonstrate overall safety and lack
      of major complications. Detailed analysis demonstrates additional safety and
      decreased failure rates of peripheral compared with neuraxial nerve blocks.
      Ultrasound technology confers additional safety and efficacy
      benefits.Increasingly, data support the safety and efficacy of novel peripheral
      nerve blocks, transversus abdominis plane and ultrasound-guided paravertebral,
      and the use of perineural catheters for both inpatients and outpatients. Regional
      anesthesia as a sole agent for surgical anesthesia and the use of regional
      anesthesia for pain in nonsurgical pain patients remains underutilized. SUMMARY:
      Paediatric specific data for regional anesthesia are available to help guide
      optimal pain management. The paediatric regional anesthesia literature lags
      behind literature available for adult populations and increased studies are
      needed for additional information for informed decision-making.

PMID- 25058200
TI  - The Statue of Liberty in Frederic-Auguste Bartholdi's studio, Paris: Paul-Joseph
      Victor Dargaud.

PMID- 25058201
TI  - High rotavirus vaccination rates continue to pay off.

PMID- 25058211
TI  - The global health security agenda in an age of biosecurity.

PMID- 25058212
TI  - Hospital consolidation, competition, and quality: is bigger necessarily better?

PMID- 25058213
TI  - A piece of my mind. Nominal competence in health care.

PMID- 25058214
TI  - Reconsideration of age as a contraindication for curative therapy of sickle cell
      disease.

PMID- 25058216
TI  - Effect of erythropoietin and transfusion threshold on neurological recovery after
      traumatic brain injury: a randomized clinical trial.
AB  - IMPORTANCE: There is limited information about the effect of erythropoietin or a
      high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE:
      To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds
      (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN,
      SETTING, AND PARTICIPANTS: Randomized clinical trial of 200 patients
      (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were
      unable to follow commands and were enrolled within 6 hours of injury at
      neurosurgical intensive care units in 2 US level I trauma centers between May
      2006 and August 2012. The study used a factorial design to test whether
      erythropoietin would fail to improve favorable outcomes by 20% and whether a
      hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable
      outcomes without increasing complications. Erythropoietin or placebo was
      initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and
      then the 24- and 48-hour doses were stopped for the remainder of the patients (n
      = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of
      7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS: Intravenous
      erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained
      with packed red blood cells. MAIN OUTCOMES AND MEASURES: Glasgow Outcome Scale
      score dichotomized as favorable (good recovery and moderate disability) or
      unfavorable (severe disability, vegetative, or dead) at 6 months postinjury.
      RESULTS: There was no interaction between erythropoietin and hemoglobin
      transfusion threshold. Compared with placebo (favorable outcome rate: 34/89
      [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first
      dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing
      regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome
      rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and
      31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28).
      There was a higher incidence of thromboembolic events for the transfusion
      threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL,
      odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE: In
      patients with closed head injury, neither the administration of erythropoietin
      nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in
      improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL
      was associated with a higher incidence of adverse events. These findings do not
      support either approach in this setting. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00313716.

PMID- 25058217
TI  - Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell
      transplantation for severe sickle cell phenotype.
AB  - IMPORTANCE: Myeloablative allogeneic hematopoietic stem cell transplantation
      (HSCT) is curative for children with severe sickle cell disease, but toxicity may
      be prohibitive for adults. Nonmyeloablative transplantation has been attempted
      with degrees of preparative regimen intensity, but graft rejection and graft-vs
      host disease remain significant. OBJECTIVE: To determine the efficacy, safety,
      and outcome on end-organ function with this low-intensity regimen for sickle cell
      phenotype with or without thalassemia. DESIGN, SETTING, AND PARTICIPANTS: From
      July 16, 2004, to October 25, 2013, 30 patients aged 16-65 years with severe
      disease enrolled in this nonmyeloablative transplant study, consisting of
      alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy),
      sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood
      stem cells (5.5-31.7 * 10(6) cells/kg) from human leukocyte antigen-matched
      siblings. MAIN OUTCOMES AND MEASURES: The primary end point was treatment success
      at 1 year after the transplant, defined as a full donor-type hemoglobin for
      patients with sickle cell disease and transfusion independence for patients with
      thalassemia. The secondary end points were the level of donor leukocyte
      chimerism; incidence of acute and chronic graft-vs-host disease; and sickle cell
      thalassemia disease-free survival, immunologic recovery, and changes in organ
      function, assessed by annual brain imaging, pulmonary function, echocardiographic
      image, and laboratory testing. RESULTS: Twenty-nine patients survived a median
      3.4 years (range, 1-8.6), with no nonrelapse mortality. One patient died from
      intracranial bleeding after relapse. As of October 25, 2013, 26 patients (87%)
      had long-term stable donor engraftment without acute or chronic graft-vs-host
      disease. The mean donor T-cell level was 48% (95% CI, 34%-62%); the myeloid
      chimerism levels, 86% (95% CI, 70%-100%). Fifteen engrafted patients discontinued
      immunosuppression medication with continued stable donor chimerism and no graft
      vs-host disease. The normalized hemoglobin and resolution of hemolysis among
      engrafted patients were accompanied by stabilization in brain imaging, a
      reduction of echocardiographic estimates of pulmonary pressure, and allowed for
      phlebotomy to reduce hepatic iron. The mean annual hospitalization rate was 3.23
      (95% CI, 1.83-4.63) the year before, 0.63 (95% CI, 0.26-1.01) the first year
      after, 0.19 (95% CI, 0-0.45) the second year after, and 0.11 (95% CI, 0.04-0.19)
      the third year after transplant. For patients taking long-term narcotics, the
      mean use per week was 639 mg (95% CI, 220-1058) of intravenous morphine
      equivalent dose the week of their transplants and 140 mg (95% CI, 56-225) 6
      months after transplant. There were 38 serious adverse events: pain and related
      management, infections, abdominal events, and sirolimus related toxic effects.
      CONCLUSIONS AND RELEVANCE: Among 30 patients with sickle cell phenotype with or
      without thalassemia who underwent nonmyeloablative allogeneic HSCT, the rate of
      stable mixed-donor chimerism was high and allowed for complete replacement with
      circulating donor red blood cells among engrafted participants. Further accrual
      and follow-up are required to assess longer-term clinical outcomes, adverse
      events, and transplant tolerance. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00061568.

PMID- 25058218
TI  - Effect of everolimus on survival in advanced hepatocellular carcinoma after
      failure of sorafenib: the EVOLVE-1 randomized clinical trial.
AB  - IMPORTANCE: Aside from the multikinase inhibitor sorafenib, there are no
      effective systemic therapies for the treatment of advanced hepatocellular
      carcinoma. OBJECTIVE: To assess the efficacy of everolimus in patients with
      advanced hepatocellular carcinoma for whom sorafenib treatment failed. DESIGN,
      SETTING, AND PARTICIPANTS: EVOLVE-1 was a randomized, double-blind, phase 3 study
      conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C
      hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed
      during or after sorafenib or who were intolerant of sorafenib. Patients were
      enrolled from 17 countries between May 2010 and March 2012. Randomization was
      stratified by region (Asia vs rest of world) and macrovascular invasion (present
      vs absent). INTERVENTIONS: Everolimus, 7.5 mg/d, or matching placebo, both given
      in combination with best supportive care and continued until disease progression
      or intolerable toxicity. Per the 2:1 randomization scheme, 362 patients were
      randomized to the everolimus group and 184 patients to the placebo group. MAIN
      OUTCOMES AND MEASURES: The primary end point was overall survival. Secondary end
      points included time to progression and the disease control rate (the percentage
      of patients with a best overall response of complete or partial response or
      stable disease). RESULTS: No significant difference in overall survival was seen
      between treatment groups, with 303 deaths (83.7%) in the everolimus group and 151
      deaths (82.1%) in the placebo group (hazard ratio [HR], 1.05; 95% CI, 0.86-1.27;
      P = .68; median overall survival, 7.6 months with everolimus, 7.3 months with
      placebo). Median time to progression with everolimus and placebo was 3.0 months
      and 2.6 months, respectively (HR, 0.93; 95% CI, 0.75-1.15), and disease control
      rate was 56.1% and 45.1%, respectively (P = .01). The most common grade 3/4
      adverse events for everolimus vs placebo were anemia (7.8% vs 3.3%,
      respectively), asthenia (7.8% vs 5.5%, respectively), and decreased appetite
      (6.1% vs 0.5%, respectively). No patients experienced hepatitis C viral flare.
      Based on central laboratory results, hepatitis B viral reactivation was
      experienced by 39 patients (29 everolimus, 10 placebo); all cases were
      asymptomatic, but 3 everolimus recipients discontinued therapy. CONCLUSIONS AND
      RELEVANCE: Everolimus did not improve overall survival in patients with advanced
      hepatocellular carcinoma whose disease progressed during or after receiving
      sorafenib or who were intolerant of sorafenib. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01035229.

PMID- 25058219
TI  - Use of whole-exome sequencing to determine the genetic basis of multiple
      mitochondrial respiratory chain complex deficiencies.
AB  - IMPORTANCE: Mitochondrial disorders have emerged as a common cause of inherited
      disease, but their diagnosis remains challenging. Multiple respiratory chain
      complex defects are particularly difficult to diagnose at the molecular level
      because of the massive number of nuclear genes potentially involved in
      intramitochondrial protein synthesis, with many not yet linked to human disease.
      OBJECTIVE: To determine the molecular basis of multiple respiratory chain complex
      deficiencies. DESIGN, SETTING, AND PARTICIPANTS: We studied 53 patients referred
      to 2 national centers in the United Kingdom and Germany between 2005 and 2012.
      All had biochemical evidence of multiple respiratory chain complex defects but no
      primary pathogenic mitochondrial DNA mutation. Whole-exome sequencing was
      performed using 62-Mb exome enrichment, followed by variant prioritization using
      bioinformatic prediction tools, variant validation by Sanger sequencing, and
      segregation of the variant with the disease phenotype in the family. RESULTS:
      Presumptive causal variants were identified in 28 patients (53%; 95% CI, 39%-67%)
      and possible causal variants were identified in 4 (8%; 95% CI, 2%-18%). Together
      these accounted for 32 patients (60% 95% CI, 46%-74%) and involved 18 different
      genes. These included recurrent mutations in RMND1, AARS2, and MTO1, each on a
      haplotype background consistent with a shared founder allele, and potential novel
      mutations in 4 possible mitochondrial disease genes (VARS2, GARS, FLAD1, and
      PTCD1). Distinguishing clinical features included deafness and renal involvement
      associated with RMND1 and cardiomyopathy with AARS2 and MTO1. However, atypical
      clinical features were present in some patients, including normal liver function
      and Leigh syndrome (subacute necrotizing encephalomyelopathy) seen in association
      with TRMU mutations and no cardiomyopathy with founder SCO2 mutations. It was not
      possible to confidently identify the underlying genetic basis in 21 patients
      (40%; 95% CI, 26%-54%). CONCLUSIONS AND RELEVANCE: Exome sequencing enhances the
      ability to identify potential nuclear gene mutations in patients with
      biochemically defined defects affecting multiple mitochondrial respiratory chain
      complexes. Additional study is required in independent patient populations to
      determine the utility of this approach in comparison with traditional diagnostic
      methods.

PMID- 25058220
TI  - Does this patient have generalized anxiety or panic disorder?: The Rational
      Clinical Examination systematic review.
AB  - IMPORTANCE: In primary care settings, generalized anxiety disorder (GAD) and
      panic disorder are common but underrecognized illnesses. Identifying accurate and
      feasible screening instruments for GAD and panic disorder has the potential to
      improve detection and facilitate treatment. OBJECTIVE: To systematically review
      the accuracy of self-report screening instruments in diagnosing GAD and panic
      disorder in adults. DATA SOURCES: We searched MEDLINE, PsycINFO, and the Cochrane
      Library for relevant articles published from 1980 through April 2014. STUDY
      SELECTION: Prospective studies of diagnostic accuracy that compared a self-report
      screening instrument for GAD or panic disorder with the diagnosis made by a
      trained clinician using Diagnostic and Statistical Manual of Mental Disorders or
      International Classification of Diseases criteria. RESULTS: We screened 3605
      titles, excluded 3529, and performed a more detailed review of 76 articles. We
      identified 9 screening instruments based on 13 articles from 10 unique studies
      for the detection of GAD and panic disorder in primary care patients Across all
      studies, diagnostic interviews determined that 257 of 2785 patients assessed had
      a diagnosis of GAD while 224 of 2637 patients assessed had a diagnosis of panic
      disorder. The best-performing test for GAD was the Generalized Anxiety Disorder
      Scale 7 Item (GAD-7), with a positive likelihood ratio of 5.1 (95% CI, 4.3-6.0)
      and a negative likelihood ratio of 0.13 (95% CI, 0.07-0.25). The best-performing
      test for panic disorder was the Patient Health Questionnaire, with a positive
      likelihood ratio of 78 (95% CI, 29-210) and a negative likelihood ratio of 0.20
      (95% CI, 0.11-0.37). CONCLUSIONS AND RELEVANCE: Two screening instruments, the
      GAD-7 for GAD and the Patient Health Questionnaire for panic disorder, have good
      performance characteristics and are feasible for use in primary care. However,
      further validation of these instruments is needed because neither instrument was
      replicated in more than 1 primary care population.

PMID- 25058221
TI  - The intention-to-treat principle: how to assess the true effect of choosing a
      medical treatment.

PMID- 25058222
TI  - Sunscreen counseling by US physicians.

PMID- 25058223
TI  - Kidney donation and risk of ESRD.

PMID- 25058224
TI  - Kidney donation and risk of ESRD.

PMID- 25058225
TI  - Kidney donation and risk of ESRD.

PMID- 25058226
TI  - Kidney donation and risk of ESRD--reply.

PMID- 25058227
TI  - Outcomes after kidney donation.

PMID- 25058228
TI  - Outcomes after kidney donation.

PMID- 25058229
TI  - Outcomes after kidney donation--reply.

PMID- 25058230
TI  - Electric uterine morcellation.

PMID- 25058235
TI  - Bicycling--pro and con.

PMID- 25058231
TI  - Electric uterine morcellation--reply.

PMID- 25058237
TI  - A window into the current state of isoprenoid research.

PMID- 25058238
TI  - Expression of protease activated receptor-1 in chronic periodontitis.
AB  - BACKGROUND: Protease activated receptor-1 (PAR1) activation by thrombin may play
      a role in repair and homeostasis of periodontal tissues. The main objective of
      this study is to investigate PAR1 expression in patients with periodontitis,
      before and after non-surgical periodontal treatment, and to associate its
      expression with the presence of inflammatory biomarkers and PAR2 expression.
      METHODS: Gingival crevicular fluid (GCF) samples and clinical parameters,
      including probing depth, clinical attachment level, bleeding on probing, and
      gingival and plaque indices, were collected from periodontally healthy
      individuals and patients with moderate chronic periodontitis (CP) before and 6
      weeks after periodontal non-surgical treatment. PAR1 and PAR2 messenger RNA
      (mRNA) at the GCF were evaluated by quantitative polymerase chain reaction
      (qPCR). Flow cytometry analysis identified the GCF PAR1-expressing cells. GCF
      inflammatory biomarkers were also determined. RESULTS: Clinical parameters were
      significantly improved after therapy (P <0.01). The qPCR analysis showed that,
      before therapy, PAR1 mRNA levels in CP were similar to controls. Periodontal
      treatment led to increased PAR1 expression in CP (P <0.05). PAR1 expression was
      inversely correlated to PAR2 expression and with interleukins 6 and 8, tumor
      necrosis factor-alpha, interferon-gamma, and matrix metalloproteinase-2 levels.
      CONCLUSIONS: Periodontal treatment results in PAR1 overexpression in the GCF, and
      PAR1 expression is associated with decreased expression of inflammatory
      biomarkers and inversely correlated to PAR2 expression in the GCF. Therefore, the
      data suggest the importance of PAR1 mediating the known anabolic actions of
      thrombin in the periodontium.

PMID- 25058239
TI  - Microwave-assisted cobinamide synthesis.
AB  - We present a new method for the preparation of cobinamide (CN)2Cbi, a vitamin B12
      precursor, that should allow its broader utility. Treatment of vitamin B12 with
      only NaCN and heating in a microwave reactor affords (CN)2Cbi as the sole
      product. The purification procedure was greatly simplified, allowing for easy
      isolation of the product in 94% yield. The use of microwave heating proved
      beneficial also for (CN)2Cbi(c-lactone) synthesis. Treatment of (CN)2Cbi with
      triethanolamine led to (CN)2Cbi(c-lactam). 

PMID- 25058240
TI  - Impact of speed cameras on trauma centers.
AB  - BACKGROUND: While studies, mostly from Europe and Australia, have examined the
      effect of speed cameras on motor vehicle collisions, limited data exist regarding
      their impact on charges and number of patients taken to Level 1 trauma centers
      (L1TCs). Because of conflicting perceptions and data on their value, speed
      cameras were implemented along select Arizona highways in 2008 but then removed
      in 2010. The hypotheses of our study were twofold. (1) Speed cameras reduce
      admissions to L1TCs, and (2) speed cameras reduce crash kinetic energy, resulting
      in lower Injury Severity Score (ISS), mortality, hospital costs, and length of
      stay (LOS). METHODS: A retrospective review of all patients admitted to L1TCs who
      were injured in motor vehicle crashes along a 26-mile segment of interstate I-10
      in urban Phoenix was performed. Patients were identified using both the Arizona
      State Trauma Registry and the Arizona Department of Transportation collision data
      for 2009 to 2011. This specific 26-mile segment of I-10 was selected because it
      contained at least one speed camera within 1 mile along its entire length from
      October 2008 to October 2010. Two time frames were evaluated: January 1 to
      December 31, 2009, when cameras were in place (2009 camera group) and January 1
      to December 31, 2011, when no cameras were in place (2011 no-camera group).
      Variables analyzed include number of collisions, number of injuries, on-scene
      mortality, trauma center admissions, number of collisions with admissions, in
      hospital mortality, ISS, hospital charges, LOS, age, sex, race, and ethnicity.
      Five confounding variables were eliminated. Analysis was performed using Fisher's
      exact test and linear regression. RESULTS: Camera removal was associated with a
      twofold increase in L1TC admissions as well as increased resource use. There were
      no significant differences between the two time frames for ISS, mortality, median
      charges, or median LOS. CONCLUSION: In this study, removal of speed cameras
      resulted in increased trauma center admissions and resource use. LEVEL OF
      EVIDENCE: Care management study, level IV.

PMID- 25058236
TI  - The diagnostic approach to monogenic very early onset inflammatory bowel disease.
AB  - Patients with a diverse spectrum of rare genetic disorders can present with
      inflammatory bowel disease (monogenic IBD). Patients with these disorders often
      develop symptoms during infancy or early childhood, along with endoscopic or
      histological features of Crohn's disease, ulcerative colitis, or IBD
      unclassified. Defects in interleukin-10 signaling have a Mendelian inheritance
      pattern with complete penetrance of intestinal inflammation. Several genetic
      defects that disturb intestinal epithelial barrier function or affect innate and
      adaptive immune function have incomplete penetrance of the IBD-like phenotype.
      Several of these monogenic conditions do not respond to conventional therapy and
      are associated with high morbidity and mortality. Due to the broad spectrum of
      these extremely rare diseases, a correct diagnosis is frequently a challenge and
      often delayed. In many cases, these diseases cannot be categorized based on
      standard histological and immunologic features of IBD. Genetic analysis is
      required to identify the cause of the disorder and offer the patient appropriate
      treatment options, which include medical therapy, surgery, or allogeneic
      hematopoietic stem cell transplantation. In addition, diagnosis based on genetic
      analysis can lead to genetic counseling for family members of patients. We
      describe key intestinal, extraintestinal, and laboratory features of 50 genetic
      variants associated with IBD-like intestinal inflammation. In addition, we
      provide approaches for identifying patients likely to have these disorders. We
      also discuss classic approaches to identify these variants in patients, starting
      with phenotypic and functional assessments that lead to analysis of candidate
      genes. As a complementary approach, we discuss parallel genetic screening using
      next-generation sequencing followed by functional confirmation of genetic
      defects. 

PMID- 25058241
TI  - In vitro transfusion of red blood cells results in decreased cytokine production
      by human T cells.
AB  - BACKGROUND: Transfusion-related immunomodulation consists of both proinflammatory
      and anti-inflammatory responses after transfusion of blood products. Stored red
      blood cells (RBCs) suppress human T-cell proliferation in vitro, but the
      mechanism remains unknown. We hypothesized that cytokine synthesis by T cells may
      be inhibited when stored RBCs are present and that suppression between fresh and
      stored RBCs would be different. METHODS: Purified human T cells were stimulated
      to proliferate with anti-CD3/anti-CD28 and then exposed to stored or fresh RBCs.
      Cells were placed in culture for 5 days. Cell culture supernatants were analyzed
      for the production of typical T-cell cytokines using multianalyte ELISArray kits.
      RESULTS: Stimulated T cells proliferated. RBC exposure markedly suppressed this
      proliferation. Interleukin 10, interleukin 17a, interferon gamma, tumor necrosis
      factor alpha, and granulocyte macrophage colony-stimulating factor were increased
      in response to stimulation but depressed in the presence of stored RBCs. The use
      of fresh RBCs also resulted in depression of these cytokines when compared with
      stimulated T cells with no RBCs; however, this depression was less pronounced.
      CONCLUSION: T-cell activation is associated with both proinflammatory and anti
      inflammatory cytokine release, comparable with patterns seen in trauma and acute
      injury. All of these responses are depressed by an exposure to stored RBCs.
      Decreased levels of these cytokines after RBC transfusion represents a potential
      contributor to the immunosuppressive complications seen in trauma patients after
      transfusion. This provides insight for future mechanistic studies to delineate
      the role of RBC transfusion in transfusion-related immunomodulation.

PMID- 25058242
TI  - The public health burden of emergency general surgery in the United States: A 10
      year analysis of the Nationwide Inpatient Sample--2001 to 2010.
AB  - BACKGROUND: Emergency general surgery (EGS) represents illnesses of very diverse
      pathology related only by their urgent nature. The growth of acute care surgery
      has emphasized this public health problem, yet the true "burden of disease"
      remains unknown. Building on efforts by the American Association for the Surgery
      of Trauma to standardize an EGS definition, we sought to describe the burden of
      disease for EGS in the United States. We hypothesize that EGS patients represent
      a large, diverse, and challenging cohort and that the burden is increasing.
      METHODS: The study population was selected from the Nationwide Inpatient Sample,
      2001 to 2010, using the AAST EGS DRG International Classification of Diseases-9th
      Rev. codes, selecting all EGS patients 18 years or older with urgent/emergent
      admission status. Rates for operations, mortality, and sepsis were compiled along
      with hospital type, length of stay, insurance, and demographic data. The chi
      test, the t test, and the Cochran-Armitage trend test were used; p < 0.05 was
      significant. RESULTS: From 2001 to 2010, there were 27,668,807 EGS admissions,
      7.1% of all hospitalizations. The population-adjusted case rate for 2010 was
      1,290 admissions per 100,000 people (95% confidence interval, 1,288.9-1,291.8).
      The mean age was 58.7 years; most had comorbidities. A total of 7,979,578
      patients (28.8%) required surgery. During 10 years, admissions increased by
      27.5%; operations, by 32.3%; and sepsis cases, by 15% (p < 0.0001). Mortality and
      length of stay both decreased (p < 0.0001). Medicaid and uninsured rates
      increased by a combined 38.1% (p < 0.0001). Nearly 85% were treated in urban
      hospitals, and nearly 40% were treated in teaching hospitals; both increased over
      time (p < 0.0001). CONCLUSION: The EGS burden of disease is substantial and is
      increasing. The annual case rate (1,290 of 100,000) is higher than the sum of all
      new cancer diagnoses (all ages/types): 650 per 100,000 (95% confidence interval,
      370.1-371.7), yet the public health implications remain largely unstudied. These
      data can be used to guide future research into improved access to care, resource
      allocation, and quality improvement efforts. LEVEL OF EVIDENCE: Epidemiologic
      study, level III.

PMID- 25058243
TI  - An acute care surgery fellowship benefits a general surgical residency.
AB  - BACKGROUND: There has been a trend toward subspecialization among general surgery
      graduates, and many subspecialists are reticent to participate in trauma care.
      This has resulted in a gap in the provision of emergency surgical care. The Acute
      Care Surgery (ACS) fellowship, incorporating trauma, critical care, and emergency
      general surgery, was developed to address this need. One of the most important
      aspects in establishing these ACS fellowships is that they do not detract from
      the existing general surgery residents' experience. METHODS: The operative case
      logs for residents and fellows were compared for the number of resident cases
      during the 3 years before the ACS fellowship and during the 3 years after the
      fellowship was established. Surveys were distributed to the general surgery
      residents addressing the impact of the fellows from the resident's perspective at
      the end of the 2011 to 2012 academic year. RESULTS: There was no significant
      change in the number of total cases; total chief resident cases; and trauma,
      thoracic, or vascular procedures done per graduate. A decrease in the number of
      liver cases performed by the residents was noted but includes the increase in
      resident complement as well as the fellowship. ACS fellow cases increased from
      172 cases in the first year to 221 cases in the second year and 295 in the third
      year. The survey showed that the residents had a very positive response to having
      the fellow as a teacher and did not feel like their operative experience was
      compromised with the addition of the ACS fellowship. CONCLUSION: The ACS fellow
      did not compromise general surgery resident experience and was regarded as an
      asset to the resident's education. An ACS fellowship can be beneficial to
      residents and fellows. LEVEL OF EVIDENCE: Care management study, level IV.

PMID- 25058244
TI  - An analysis of prehospital deaths: Who can we save?
AB  - BACKGROUND: Since their inception in the late 1970s, trauma networks have saved
      thousands of lives in the prehospital setting. However, few recent works have
      been done to evaluate the patients who die in the field. Understanding the
      epidemiology of these deaths is crucial for trauma system performance evaluation
      and improvement. We hypothesized that specific patterns of injury could be
      identified and targeted for intervention. METHODS: Medical examiner reports in a
      large, urban county were reviewed including all trauma deaths during 2011 that
      were not transported to a hospital (i.e., died at the scene) or dead on arrival.
      Age, sex, date of death, mechanism, and list of injuries were recorded. An expert
      panel reviewed each case to determine the primary cause of death, and if the
      patient's death was caused by potentially survivable injuries or nonsurvivable
      injuries. RESULTS: A total of 512 patients were included. Patients were 80% male,
      died mostly of blunt (53%) and penetrating (46%) causes, and included 21%
      documented suicides. The leading cause of death was neurotrauma (36%), followed
      by hemorrhage (34%), asphyxia (15%), and combined neurotrauma/hemorrhage (15%).
      The anatomic regions most frequently injured were the brain (59%), chest (54%),
      and abdomen (35%). Finally, 29% of the patient deaths were classified as a result
      of potentially survivable injuries given current treatment options, mostly from
      hemorrhage and chest injuries. CONCLUSION: More than one of every five trauma
      deaths in our study population had potentially survivable injuries. In this
      group, chest injuries and death via hemorrhage were predominant and suggest
      targets for future research and implementation of novel prehospital
      interventions. In addition, efforts targeting suicide prevention remain of great
      importance. LEVEL OF EVIDENCE: Epidemiologic study, level V.

PMID- 25058245
TI  - Trauma remains a surgical disease from cradle to grave.
AB  - BACKGROUND: A dramatic rise in nonoperative management of many blunt and some
      penetrating traumatic injuries has occurred during the past four decades. This
      trend has lead some to suggest that trauma is no longer a surgical disease. We
      questioned what role the trauma surgeon plays in the care of the injured patient.
      We hypothesized that surgical intervention and judgment are still often required
      in both injured children and adults. METHODS: We queried the trauma databases at
      two academic Level I trauma centers (adult and pediatric) for all patients
      admitted for trauma who underwent an inpatient operation between July 1, 2009,
      and June, 31, 2013, as well as those patients with "potentially operative
      injury." Potentially operative injury was defined as the presence of liver or
      splenic laceration of any grade or hemothorax in patients who did not undergo an
      inpatient operation. For analysis, we divided patients into groups based on age.
      We differentiated infants (0-1 years), toddlers (2-5 years), school-aged children
      (6-12 years), adolescents (13-15 years), young adults (16-21 years), adults (22
      40 years), middle-aged adults (41-50 years), late middle-aged adults (51-64
      years), and elderly (>65 years). Data collected included demographic information
      and number of operations performed in each patient based on surgical service
      (neurosurgery, trauma surgery, orthopedic surgery, and other surgical services).
      RESULTS: During this 4-year study period, 11,611 patients were admitted to the
      trauma service, 6,334 (54.6%) of whom underwent an inpatient operation and
      another 492 (4.2%) of whom had potentially operative injury. Across all age
      groups, orthopedic procedures accounted for the greatest percentage of inpatient
      procedures (>70% of inpatient operations performed). Neurosurgical intervention
      accounted for less than 10% of inpatient surgical interventions, and general
      surgical procedures performed by trauma surgeons accounted for 17.1%. More than
      half of all general surgical procedures were performed in the patients who
      required a hospital stay of more than 7 days (67.2% among all patients).
      CONCLUSION: More than half of patients admitted following traumatic injury
      require operative intervention. This rate remains stable across all age groups.
      Our data emphasize the continued need for surgeons to stay engaged in the care of
      the trauma patient, particularly those most critically injured patients who will
      require prolonged hospital stay. LEVEL OF EVIDENCE: Epidemiologic study, level
      III. Care management study, level IV.

PMID- 25058246
TI  - Computed tomography scans with intravenous contrast: low incidence of contrast
      induced nephropathy in blunt trauma patients.
AB  - BACKGROUND: Computed tomography (CT) with intravenous (IV) contrast is an
      important step in the evaluation of the blunt trauma patient; however, the risk
      for contrast-induced nephropathy (CIN) in these patients still remains unclear.
      The goal of this study was to describe the rate of CIN in blunt trauma patients
      at a Level 1 trauma center and identify the risk factors of developing CIN.
      METHODS: After internal review board approval, we reviewed our Level 1 trauma
      registry to identify blunt trauma patients admitted during a 1-year period. Chart
      review was used to identify patient demographics, creatinine levels, and vital
      signs. CIN was defined as an increase in creatinine by 0.5 mg/dL from admission
      after undergoing CT with IV contrast. RESULTS: Four percent of patients developed
      CIN during their admission following receipt of IV contrast for CT; 1% had
      continued renal impairment on discharge. No patients required dialysis during
      their admission. Diabetic patients had an increased rate of CIN, with 10% rate of
      CIN during admission and 4% at discharge. In multivariate analysis, only
      preexisting diabetes and Injury Severity Score (ISS) of greater than 25 were
      independently associated with risk for CIN. CONCLUSION: The rate of CIN in trauma
      patients following CT scan with IV contrast is low. Diabetes and ISS were
      independent risk factors of development of CIN in trauma patients. LEVEL OF
      EVIDENCE: Epidemiologic/prognostic study, level III.

PMID- 25058247
TI  - Characterization of the hypercoagulable state following severe orthopedic trauma.
AB  - BACKGROUND: Acute traumatic coagulopathy develops in seriously injured patients,
      which is followed by a paradoxical hypercoagulable state. The hypercoagulable
      state contributes to venous thromboembolism, and yet, there are no sensitive
      tests available to detect it. The aim of this study was to characterize the
      hypercoagulable state caused by major orthopedic trauma using the overall
      hemostatic potential (OHP) assay. METHODS: Major orthopedic trauma patients
      admitted during a 7-month period in 2012 were included in the study. Blood
      samples were drawn 1 hour before surgery, then 1, 7, 24 hours and 3, 5, 10, and
      42 days postoperatively. The assay parameters were determined and analyzed
      according to injury severity (polytrauma or nonpolytrauma), type of surgical
      intervention, and shock status. Values were compared with 20 healthy controls.
      RESULTS: Forty-one consecutive patients were enrolled (age, 41.5 +/- 2.7 years;
      70% male; Injury Severity Score [ISS], 21.5 +/- 2.1). Hypercoagulability based on
      OHP was present in the preoperative sample compared with the controls (OHP, 13.8
      +/- 1.4 U vs. 8.1 +/- 0.5 U; p = 0.020) and then further elevated after surgery
      (1 hour postoperative, 17.8 +/- 2.0 U vs. preoperative, 13.8 +/- 1.4 U, p =
      0.008). Polytrauma patients were more hypercoagulable than nonpolytrauma at the
      preoperative sample time (17.7 +/- 2.6 U vs. 10.7 +/- 1.2 U, p = 0.040) and
      postoperative period (24.3 +/- 3.4 U vs. 11.9 +/- 1.4 U, p = 0.006). The OHP for
      patients undergoing open pelvic surgery (28.3 +/- 3.0 U) was higher than both
      intramedullary nailing (16.2 +/- 2.0 U) and percutaneous pelvic surgery (17.0 +/-
      1.7 U) on Day 5 (p < 0.05). Patients demonstrated a higher OHP than controls did
      at all time points, except at 6 weeks (patients, 10.8 +/- 1.7 U vs. controls, 8.1
      +/- 0.5 U; p = 0.400). CONCLUSION: The OHP assay detected the hypercoagulable
      state following major orthopedic trauma and surgical intervention, which was
      present for 10 days postoperatively. The extent of hypercoagulability could be
      associated with polytrauma and the type of surgical intervention; however,
      further studies are needed to confirm this. LEVEL OF EVIDENCE: Epidemiologic
      study, level III.

PMID- 25058248
TI  - Isolated traumatic brain injury and venous thromboembolism.
AB  - BACKGROUND: Traumatic brain injury (TBI) is considered an independent risk factor
      of venous thromboembolism (VTE). However, the role of TBI severity in VTE risk
      has not been determined. We hypothesized that increased severity of brain injury
      in patients with isolated TBI (iTBI) is associated with an increased incidence of
      VTE. METHODS: The records of patients admitted from June 2006 to December 2011
      were reviewed for injury data, VTE risk factors, results of lower extremity
      surveillance ultrasound, and severity of TBI. Patients were identified by DRG
      International Classification of Diseases-9th Rev. codes for TBI, and only those
      with a nonhead Abbreviated Injury Scale (AIS) score of 1 or lower, indicating
      minimal associated injury, were included. The association of iTBI and VTE was
      determined using a case-control design. Among iTBI patients, those diagnosed with
      VTE (cases) were matched for age, sex, and admission year to those without VTE
      (controls). Data were analyzed using conditional logistic regression. RESULTS:
      There were 345 iTBI patients: 41 cases (12%) and 304 controls (88%). A total of
      151 controls could not be matched to an appropriate case and were excluded. Of
      the remaining 153 controls, 1 to 16 controls were matched to each of the 41 VTE
      cases. Compared with the controls, the cases had a higher mean head-AIS score
      (4.4 vs. 3.9, p = 0.001) and overall Injury Severity Score (20.4 vs. 16.8, p =
      0.001). Following adjustment for all factors found to be associated with VTE
      (ventilator days, central line placement, operative time > 2 hours,
      chemoprophylaxis, history of VTE, and history of cancer), the cases were
      significantly more likely to have a greater head injury severity (head-AIS score
      >= 5; odds ratio, 5.25; 95% confidence interval, 1.59-17.30; p = 0.006).
      CONCLUSION: The incidence of VTE in iTBI patients was significantly associated
      with the severity of TBI. VTE surveillance protocols may be warranted in these
      high-risk patients, as early detection of VTE could guide subsequent therapy.
      LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

PMID- 25058249
TI  - Does traumatic brain injury increase the risk for venous thromboembolism in
      polytrauma patients?
AB  - BACKGROUND: Trauma is a major risk factor for venous thromboembolism (VTE).
      Traumatic brain injury (TBI) is generally considered to further increase the VTE
      risk, which should prompt routine thromboprophylaxis. However, the associated
      risk for intracranial hemorrhage often delays anticoagulants. We test the
      hypothesis that TBI associated with polytrauma results in a higher rate of VTE
      than polytrauma without TBI. METHODS: From August 2011 to June 2013, a
      prospective observational trial with informed consent was performed in 148
      intensive care unit (ICU) patients with a Greenfield Risk Assessment Profile
      score of 10 or greater. RESULTS: Demographics, Greenfield Risk Assessment Profile
      scores, the incidence of polytrauma, and mortality were similar, but TBI patients
      had worse Injury Severity Scores (ISS) (32 vs. 22), longer ICU lengths of stay
      (21 days vs. 12 days), more hypercoagulable thromboelastogram values on admission
      (94% vs. 79%), more received unfractionated heparin prophylaxis (65% vs. 36%),
      and the prophylaxis start date was more than a day later (all p < 0.05).
      Nevertheless, the VTE rate with TBI was similar to that without TBI (25% vs. 26%,
      p = 0.507). Furthermore, VTE occurred at similar time points after ICU admission
      with and without TBI. In both groups, about 30% of the VTEs were detected within
      2 days of ICU admission and 50% of the VTEs occurred within 10 days of admission
      despite chemical and mechanical thromboprophylaxis. CONCLUSION: In complex
      polytrauma patients who survived to ICU admission and who were prescreened for
      high VTE risk, TBI did not further increase the risk for VTE. The most likely
      explanation is that no single risk factor is necessary or sufficient for VTE
      development, especially in those who routinely receive chemical and mechanical
      thromboprophylaxis. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 25058250
TI  - Negative pleural suction in thoracic trauma patients: A randomized controlled
      trial.
AB  - BACKGROUND: The study aimed to establish the benefits of using chest tubes with
      negative pleural suction against trapped water in patients with penetrating or
      blunt chest trauma who underwent tube thoracostomy, in terms of the incidence of
      complications, such as persistent air leak, clotted hemothorax, empyema, and
      duration of stay. METHODS: Patients who underwent tube thoracostomy because of
      traumatic pneumothorax, hemothorax, or hemopneumothorax were randomly assigned
      into one of two groups: in Group 1, the three-bottle drainage system was
      connected to a negative suction; in Group 2, no suction was given. Patients who
      required mechanical ventilation or emergency surgery (thoracotomy or
      thoracoscopy) either at the time of admission to the institution or immediately
      after the tube thoracostomy, patients who had histories of thoracic procedures or
      chronic pulmonary diseases (chronic obstructive pulmonary disease, diffuse
      interstitial lung disease), and patients with multiple injuries with severe
      traumatic brain injury and a Glasgow Coma Scale (GCS) score less than 8 of 15
      were excluded from the study. Hospital stay, duration of tube thoracostomy,
      prolonged fistula, and other clinical variables were compared. RESULTS: One
      hundred ten patients were included, 56 in the group with suction and 54 in the
      group without suction. There were no differences in the demographic
      characteristics of each group. There were no differences between the groups in
      terms of hospital stay (p = 0.22), duration of tube thoracostomy (p = 0.35) (3
      days in each group), or complications. However, the probability of air leak
      presence in time was greater for the Group 1 patients with negative suction
      versus the Group 2 patients (p = 0.023). CONCLUSION: The use of negative pleural
      suction did not demonstrate advantages over the three-bottle chest drainage
      system without suction in patients with uncomplicated traumatic pneumothorax,
      hemothorax, or hemopneumothorax. LEVEL OF EVIDENCE: Therapeutic study, level II.

PMID- 25058251
TI  - Thoracic ultrasound can predict safe removal of thoracostomy tubes.
AB  - BACKGROUND: Chest x-rays (CXRs) have been the mainstay for the management of
      thoracostomy tubes (TTs), but reports that ultrasound (US) may be more sensitive
      for detection of pneumothorax (PTX) continue to increase. The objective of this
      study was to determine if US is safe and effective for the detection of PTX
      following TT removal. METHODS: This was a retrospectively reviewed, prospective
      process improvement project involving patients who had a TT managed by the
      surgical team. Bedside US was performed by experienced surgeon sonographers
      before and after TT removal. Initially, a CXR was obtained before and after TT
      removal, with sonographers blinded to CXR findings. Subsequently, routine CXR was
      no longer obtained, and TT removal was determined by US. RESULTS: One hundred
      twenty-nine TTs were placed during the study. Initially, water seal and postpull
      US were performed on 49 TTs, with 6 tubes having only postpull imaging. US was
      able to detect all significant PTXs seen on CXR but identified one false
      positive. Subsequently, 74 TTs had US imaging on water seal and after pull. Water
      seal US allowed the safe removal of 70% of the TTs. Twenty patients had no slide
      on water seal US and required follow-up CXR. Most importantly, US had a 100%
      negative predictive value for PTX during TT removal. CONCLUSION: US is safe and
      effective for the rapid diagnosis of PTX. This has allowed the discontinuation of
      routine CXR for the evaluation of PTX during TT removal for patients with
      adequate lung slide seen on thoracic US lung windows. LEVEL OF EVIDENCE:
      Diagnostic test, level II. Therapeutic study, level IV.

PMID- 25058252
TI  - Contrasting patient, family, provider, and societal goals at the end of life
      complicate decision making and induce variability of care after trauma.
AB  - BACKGROUND: End-of-life (EoL) decision making during critical illness and injury
      is important in facilitating compassionate care that is congruent with patient,
      family, and societal expectations. Herein, we evaluate factors that may effect
      and induce variability in practitioner EoL decision making, particularly years in
      practice, use of advance directives (ADs), and cost. METHODS: An anonymous,
      online survey was offered to all active members of the Eastern Association for
      the Surgery of Trauma (n = 1,359) in June 2012. Demographic information and a
      series of questions dealing with common potentially influential factors were
      included. Responses were 5-point Likert scale based. RESULTS: A total of 375
      responses (27.6%) were received. Ninety-two percent of the respondents were
      physicians, 70% were male, and 77% were from Level 1 trauma centers. Of
      respondents, 65.8% rely on family to make EoL decisions most or all of the time,
      while 80.7% feel family members are rarely or only sometimes in appropriate
      emotional states to make such choices. A significant number of practitioners felt
      comfortable making decisions without family input at all, more so with
      experienced practitioners as compared with those in practice for less than 15
      years (38.2% and 24.1% respectively, p < 0.01).Of the practitioners, 59.6% rely
      on ADs most or all of the time, only 61.1% agree or strongly agree that ADs are
      useful, and only 56.3% feel families follow their loved one's ADs most or all of
      the time. A patient's family support or ability to pay for aftercare was rarely
      or never considered important by 80.1% of the practitioners, despite 85.1%
      reporting that quality of life postillness/injury was important most or all of
      the time. CONCLUSION: Practitioner comfort and motivation to influence EoL
      decision making varies with experience level. ADs are not uniformly perceived to
      be helpful, and costs are uncommonly considered. To improve EoL quality, these
      factors need to be considered. LEVEL OF EVIDENCE: Care management study, level
      IV.

PMID- 25058253
TI  - Use of two grading systems in determining risks associated with timing of
      fracture fixation.
AB  - BACKGROUND: The early appropriate care (EAC) protocol and clinical grading system
      (CGS) propose criteria that suggest timing of definitive fracture fixation by
      assessing risk for complications. This study applies these criteria to a cohort
      of patients with orthopedic injuries and determines clinical outcomes for groups
      stratified by risk and timing of fracture fixation. METHODS: This retrospective
      work was performed at a Level I trauma center. Patients with operative femur,
      pelvis, acetabulum, and/or thoracolumbar spine injuries were included. Fractures
      were treated surgically, either early or delayed. Patients were retrospectively
      categorized into low- or high-risk groups using the EAC protocol and described as
      stable, borderline, unstable, or in extremis using a modified CGS (mCGS).
      RESULTS: In the EAC analysis, low-risk patients treated early had fewer
      complications compared with delayed treatment. Among high-risk patients, no
      significant difference was noted. With the use of the mCGS, stable patients
      treated early had fewer complications compared with delayed patients. No
      difference in complications was detected for unstable and in extremis patients.
      Borderline patients treated early had fewer complications compared with delayed
      treatment, although results were not supported by sensitivity analysis.
      CONCLUSION: The EAC protocol can effectively distinguish patients who are at high
      risk for complications if treated early. Early treatment in the low-risk group
      was associated with fewer complications. The mCGS differentiates stable patients
      who benefit from early definitive treatment of fractures as well as severely
      injured patients (unstable or in extremis) who may benefit from damage-control
      orthopedics. Borderline patients may also benefit from early definitive
      treatment, but criteria defining borderline patients require further study. LEVEL
      OF EVIDENCE: Prognostic study, level III.

PMID- 25058254
TI  - Work-related injuries in a state trauma registry: relationship between industry
      and drug screening.
AB  - BACKGROUND: Work-related injuries exert a great financial and economic burden on
      the US population. The study objectives were to identify the industries and
      occupations associated with worker injuries and to determine the predictors for
      injured worker drug screening in trauma centers. METHODS: Work-related injury
      cases were selected using three criteria (expected payer source of workers'
      compensation, industry-related e-codes, and work-related indicator) from the
      Kentucky Trauma Registry data set for years 2008 to 2012. Descriptive analyses
      and multiple logistic regression were performed on the work-related injury cases.
      RESULTS: The "other services" and construction industry sectors accounted for the
      highest number of work-related cases. Drugs were detected in 55% of all drug
      screened work-related trauma cases. Higher percentages of injured workers tested
      positive for drugs in the natural resources and mining, transportation and public
      utilities, and construction industries. In comparison, higher percentages of
      injured workers in the other services as well as transportation and public
      utilities industries were drug screened. Treatment at Level I trauma centers and
      Glasgow Coma Scale (GCS) scores indicating a coma or severe brain injury were
      both significant independent predictors for being screened for drugs; industry
      was not a significant predictor for being drug screened. The injured worker was
      more likely to be drug screened if the worker had a greater than mild injury,
      regardless of whether the worker was an interfacility transfer. CONCLUSION: These
      findings indicate that there may be elevated drug use or abuse in natural
      resources and mining, transportation and public utilities, as well as
      construction industry workers; improved identification of the specific drug types
      in positive drug screen results of injured workers is needed to better target
      prevention efforts. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 25058255
TI  - Basic endovascular skills for trauma course: bridging the gap between
      endovascular techniques and the acute care surgeon.
AB  - BACKGROUND: The use of catheter-based skills is increasing in the field of
      vascular trauma. Virtual reality simulation (VRS) is a well-established means of
      endovascular skills training, and potentially lifesaving skills such as
      resuscitative endovascular balloon occlusion of the aorta (REBOA) may be obtained
      through VRS. METHODS: Thirteen faculty members in the Division of Trauma and
      Critical Care performed REBOA six times on the Vascular Intervention System
      Training Simulator-C after a didactic and instructional session. Subjects were
      excluded if they had taken a similar endovascular training course, had additional
      training in endovascular surgery, or had performed this procedure in the clinical
      setting. Performance metrics included procedural time; accurate placement of
      guide wire, sheath, and balloon; correct sequence of steps; economy of motion;
      and safe use of endovascular tools. A precourse and postcourse test and
      questionnaire were performed by each subject. RESULTS: Significant improvements
      in knowledge (p = 0.0013) and procedural task times (p < 0.0001) were observed at
      the completion of the course. No correlation was observed with endovascular
      experience in residency, number of central and arterial catheters placed weekly,
      or other parameters. All trainees strongly agreed that the course was beneficial,
      and the majority would recommend this training to other acute care surgeons.
      CONCLUSION: Damage control endovascular procedures can be effectively taught
      using VRS. Significant improvements in procedural time and knowledge can be
      achieved regardless of endovascular experience in residency, years since
      residency, or other parameters. Novice interventionalists (acute care surgeons)
      can add a specific skill set (REBOA) to their existing core competencies, which
      has the potential to improve the survival and/or outcomes of severely injured
      patients.

PMID- 25058256
TI  - Effect of valproic acid and injury on lesion size and endothelial glycocalyx
      shedding in a rodent model of isolated traumatic brain injury.
AB  - BACKGROUND: In isolated traumatic brain injury (TBI), little is known about the
      endothelial response and the effects of endothelial glycocalyx shedding. We have
      previously shown that treatment with valproic acid (VPA) improves outcomes
      following TBI and hemorrhagic shock.In this model, we hypothesized that severe
      isolated TBI would cause shedding of the endothelial glycocalyx, as measured by
      serum syndecan-1 (sSDC-1) levels. We further hypothesized that VPA treatment
      would reduce this response and reduce lesion size volume. METHODS: Forty Sprague
      Dawley rats were allocated to TBI + VPA (n = 8), TBI + saline vehicle control
      infusion (n = 8), sham + saline vehicle control infusion (n = 6), or sham + VPA
      (n = 8). TBI animals were subjected to severe controlled cortical impact and
      killed 6 hours after injury. VPA 300 mg/kg was given as an intravenous bolus 30
      minutes after injury. Serum samples were analyzed for sSDC-1, and lesion size was
      determined on Nissl-stained cryosections. RESULTS: sSDC-1 was significantly
      elevated in injured compared with uninjured animals at 3 hours (p = 0.0009) and 6
      hours (p = 0.0007) after injury. This effect was significantly more pronounced in
      the animals treated with VPA (p = 0.019) 3 hours after injury, in which sSDC-1
      levels were also significantly inversely correlated with lesion size (rho = 
      0.55, p = 0.038).Lesion size was significantly smaller in TBI + VPA (40.45 mm +/-
      13.83 mm) as compared with vehicle control (59.57 mm +/- 16.83 mm) (p = 0.023).
      CONCLUSION: Severe isolated TBI caused shedding of the endothelial glycocalyx.
      Treatment with VPA was associated with increased glycocalyx shedding and reduced
      lesion size volume in injured animal.

PMID- 25058257
TI  - Mandatory health care insurance is associated with shorter hospital length of
      stay among critically injured trauma patients.
AB  - BACKGROUND: The implementation of the Affordable Care Act stimulated interest in
      outcomes of patients in Massachusetts, a state mandating health insurance as of
      2006. We sought to determine the impact of an insurance mandate on hospital use
      and outcomes among trauma intensive care unit (ICU) patients. METHODS: This is a
      retrospective cohort study of trauma patients admitted to the ICU conducted at an
      academic, trauma center. Patients before (2004-2006) and after (2008-2012) the
      implementation of mandatory health insurance were compared using propensity
      matching to control for confounders. Outcomes were hospital length of stay (LOS),
      ICU LOS, in-hospital mortality, and discharge disposition. RESULTS: Overall,
      1,668 trauma patients were included, with 530 matched on the propensity score in
      each group. Hospital LOS decreased by a median of 2.0 days, from 9.0 days
      (interquartile range, 4-15 days; p < 0.01) before to 7.0 days (interquartile
      range, 4-14) after implementation of the legislation. There were no differences
      in ICU LOS (3.0 days to 3.0 days, p = 0.44) and mortality (odds ratio [OR], 1.16;
      95% confidence interval [CI], 0.83-1.63). Compared with discharges to home, the
      patients were more likely to be discharged home with home health services after
      the legislation (OR, 1.70; 95% CI, 1.08-2.68), but there was no significant
      change in the likelihoods of the patients being discharged to skilled nursing and
      rehabilitation facilities (OR, 0.97; 95% CI, 0.72-1.31). CONCLUSION:
      Implementation of health care reform was associated with a decrease in hospital
      LOS, with an increase in use of home health services and no change in ICU LOS and
      mortality among trauma ICU patients at our institution. LEVEL OF EVIDENCE:
      Prognostic/epidemiologic study, level III.

PMID- 25058258
TI  - Glasgow motor scale alone is equivalent to Glasgow Coma Scale at identifying
      children at risk for serious traumatic brain injury.
AB  - BACKGROUND: Glasgow Coma Scale (GCS) is a validated assessment of neurologic
      state. Assessment of the eye and verbal components is difficult to reliably
      obtain in children. We hypothesized that an abnormal Glasgow motor scale (GMS)
      score alone will reliably identify children with serious traumatic brain injury
      (TBI). METHODS: We reviewed all children with a diagnosis of TBI from 2002 to
      2011 at two urban Level I pediatric trauma centers. We used logistic regression
      to model GCS, GMS, Glasgow verbal scale (GVS), and Glasgow eye scale (GES) for
      seven outcomes: need for craniotomy, intracranial pressure monitoring, admission
      to the intensive care unit, hospital stay of 5 days or longer, discharge to
      rehabilitation, dependence on caretakers at follow-up, and survival to hospital
      discharge. We then used three measures of fit analysis to determine which scale
      offered the best fit for each of the outcomes. RESULTS: A total of 2,341 patients
      (mean [SD] age, 6.9 [5.8] years; 64.7% male) with TBI and GCS data available were
      identified. The median GCS on presentation was 15 (interquartile range [IQR], 8
      15); the median GMS on presentation was 6 (IQR, 4-6). The median GVS was 5 (IQR,
      1-5), and the median GES was 4 (IQR, 2-4). GCS as a whole offered the best fit
      for the data in predicting need for intensive care unit admission, need for
      intracranial pressure monitoring, prolonged hospital length of stay, and
      discharge to rehabilitation but was equivalent to GMS in predicting need for
      craniotomy, survival to hospital discharge, or dependence on a caretaker at
      follow-up. Further analysis revealed that GMS was more predictive of these
      outcomes than GVS + GES, indicating that GMS provides the greatest contribution
      to the predictive ability of the GCS. CONCLUSION: GMS score alone and GCS do not
      differ in identifying children with serious TBI. Eliminating the eye and verbal
      components of GCS does not adversely affect the accuracy of this tool to identify
      children at risk for serious TBI. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 25058259
TI  - The impact of solid organ injury management on the US health care system.
AB  - BACKGROUND: Since the 1980s, there has been a paradigm shift toward nonoperative
      management of stable patients with solid organ injury. The impact of this
      practice change on national health care expenditure has not been well
      characterized. METHODS: Hospital discharge data from the Healthcare Cost
      Utilization Project Nationwide Inpatient Sample from every other year spanning
      1994 to 2010 were studied using patients with a primary diagnosis of splenic and
      liver injury. Cost analysis was performed using cost-to-charge ratios, where
      actual costs of hospitalization with current management practices were compared
      with theoretical costs projecting 1994 practice patterns. Length of stay (LOS)
      was evaluated similarly to costs. Mortality risk was established using the
      validated Trauma Mortality Prediction Model. RESULTS: Data from 29,409 adult
      patients with splenic injury and 14,704 with liver injury were used for cost and
      LOS analysis. The proportion of patients undergoing nonoperative management
      increased from 38% to 67% for splenic injury and from 62% to 81% for liver
      injury. The mean cost for splenic injury dropped by $8,421 per patient, a net
      reduction in total costs per admission of 29.5% (p < 0.0001), resulting in a mean
      estimated $12 million per year reduction in cost of care in 2008 alone. For liver
      injury, cost has been reduced by $8,822 per patient, a 27.7% reduction (p <
      0.0001), with a net $17 million per year savings. LOS has been reduced by a mean
      +/- SE of 1.9 +/- 0.7 days per splenic injury (p = 0.0001) and 2.2 +/- 0.9 days
      for liver injury (p = 0.0001). Mortality rate of high-risk patients (Trauma
      Mortality Prediction Model > 0.3) treated conservatively for splenic injury fell
      from 30% to 20% and from 64% to 18% for liver injury. CONCLUSION: The trend
      toward nonoperative management of solid organ injury has resulted in a
      substantial decrease in health care expenditure and LOS while improving mortality
      for high-risk patients. Advances in trauma care can have significant impact on
      the cost of health care. LEVEL OF EVIDENCE: Economic analysis, level III.

PMID- 25058260
TI  - Virtual-world hospital simulation for real-world disaster response: Design and
      validation of a virtual reality simulator for mass casualty incident management.
AB  - BACKGROUND: Mass casualty incidents are unfortunately becoming more common. The
      coordination of mass casualty incident response is highly complex. Currently
      available options for training, however, are limited by either lack of realism or
      prohibitive expense and by a lack of assessment tools. Virtual worlds represent a
      potentially cost-effective, immersive, and easily accessible platform for
      training and assessment. The aim of this study was to assess feasibility of a
      novel virtual-worlds-based system for assessment and training in major incident
      response. METHODS: Clinical areas were modeled within a virtual, online hospital.
      A major incident, incorporating virtual casualties, allowed multiple clinicians
      to simultaneously respond with appropriate in-world management and transfer plans
      within limits of the hospital's available resources. Errors, delays, and
      completed actions were recorded, as well as Trauma-NOnTECHnical Skills (T
      NOTECHS) score. Performance was compared between novice and expert clinician
      groups. RESULTS: Twenty-one subjects participated in three simulations: pilot (n
      = 7), novice (n = 8), and expert groups (n = 6). The novices committed more
      critical events than the experts, 11 versus 3, p = 0.006; took longer to treat
      patients, 560 (299) seconds versus 339 (321) seconds, p = 0.026; and achieved
      poorer T-NOTECHS scores, 14 (2) versus 21.5 (3.7), p = 0.003, and technical
      skill, 2.29 (0.34) versus 3.96 (0.69), p = 0.001. One hundred percent of the
      subjects thought that the simulation was realistic and superior to existing
      training options. CONCLUSION: A virtual-worlds-based model for the training and
      assessment of major incident response has been designed and validated. The
      advantages of customizability, reproducibility, and recordability combined with
      the low cost of implementation suggest that this potentially represents a
      powerful adjunct to existing training methods and may be applicable to further
      areas of surgery as well.

PMID- 25058261
TI  - Complications to evaluate adult trauma care: An expert consensus study.
AB  - BACKGROUND: Complications affect up to 37% of patients hospitalized for injury
      and increase mortality, morbidity, and costs. One of the keys to controlling
      complications for injury admissions is to monitor in-hospital complication rates.
      However, there is no consensus on which complications should be used to evaluate
      the quality of trauma care. The objective of this study was to develop a
      consensus-based list of complications that can be used to assess the acute phase
      of adult trauma care. METHODS: We used a three-round Web-based Delphi survey
      among experts in the field of trauma care quality with a broad range of clinical
      expertise and geographic diversity. The main outcome measure was median
      importance rating on a 5-point Likert scale (very low to very high);
      complications with a median of 4 or greater and no disagreement were retained. A
      secondary measure was the perceived quality of information on each complication
      available in patient files. RESULTS: Of 19 experts invited to participate, 17
      completed the first (brainstorming) round and 16 (84%) completed all rounds. Of
      73 complications generated in Round 1, a total of 25 were retained including
      adult respiratory distress syndrome, hospital-acquired pneumonia, sepsis, acute
      renal failure, deep vein thrombosis, pulmonary embolism, wound infection,
      decubitus ulcers, and delirium. Of these, 19 (76%) were perceived to have high
      quality or very high-quality information in patient files by more than 50% of the
      panel members. CONCLUSION: This study proposes a consensus-based list of 25
      complications that can be used to evaluate the quality of acute adult trauma
      care. These complications can be used to develop an informative and actionable
      quality indicator to evaluate trauma care with the goal of decreasing rates of
      hospital complications and thus improving patient outcomes and resource use. DRG
      International Classification of Diseases codes are provided.

PMID- 25058262
TI  - When birds can't fly: an analysis of interfacility ground transport using
      advanced life support when helicopter emergency medical service is unavailable.
AB  - BACKGROUND: Helicopter emergency medical service (HEMS) transport of trauma
      patients is costly and of unproven benefit. Recent retrospective studies fail to
      control for crew expertise and therefore compare highly trained advance life
      support with less-trained basic life support crews. The purpose of our study was
      to compare HEMS with ground, interfacility transport while controlling for crew
      training. We hypothesized that patients transported by HEMS would experience
      shorter interhospital transport time and reduced mortality. METHODS: Our National
      Trauma Registry of the American College of Surgeons database was retrospectively
      queried to identify consecutive interfacility, hospital transfers (January 1,
      2008, to November 1, 2012) to our Level I trauma center. Transfers were
      stratified by transportation vehicle (i.e., HEMS vs. ground transport). Cohorts
      were compared across standard demographic and clinical variables using univariate
      analysis. Multivariate logistic regression was performed to determine the
      association of these variables with mortality. RESULTS: The HEMS (n = 2,190) and
      ground (n = 223) cohorts were well matched overall, with no significant
      differences for demographics, injury severity, physiology, hospital length of
      stay, or complications. Median (interquartile range) time to definitive care was
      significantly lower for HEMS (150 [114] minutes vs. 255 [157] minutes, p <
      0.001), without change in mortality (9.0% vs. 8.1%, p = 0.71). Multivariate
      logistic regression did not identify an association between transport mode and
      mortality. CONCLUSION: Despite faster interfacility transport times, HEMS offered
      no mortality benefit compared with ground when crew expertise was controlled for,
      contradicting recent large, retrospective National Trauma Data Bank studies. Our
      study may represent the best approximation of a prospective study by focusing on
      patients deemed worthy of HEMS by referring providers. Although HEMS may seem
      intuitively beneficial for time-dependent injuries, larger studies with a similar
      methodology are warranted to justify the cost and risk of HEMS and identify
      subsets of patients who may benefit. LEVEL OF EVIDENCE: Prognostic/epidemiologic
      study, level III.

PMID- 25058263
TI  - Emergency laparoscopy: a new emerging discipline for treating abdominal
      emergencies attempting to minimize costs and invasiveness and maximize outcomes
      and patients' comfort.

PMID- 25058264
TI  - A temporary stent graft as a new shunt for juxtahepatic vena cava injury.
AB  - BACKGROUND: Juxtahepatic vena cava (JHC) injury is difficult to handle because of
      JHC injury's specific position and liver obstruction. The traditional shunt
      method initially appeared to be useful but ultimately failed. Simple and
      effective methods are needed to solve it. METHODS: Firstly, the clinical data,
      including the computed tomography images, of 120 patients were collected. In
      addition, a JHC digital model was constructed based on computed tomography
      images. According to the digital model data, a circulation loop simulating the
      blood flow in the JHC was established. Secondly, we analyzed the hemodynamics of
      a JHC shunt with pig blood. Finally, the new shunt was designed based on the data
      obtained. The shunt consists of a covered stent and transfer device and was
      tested. RESULTS: The JHC has a three-dimensional cylindrical structure. The mean
      (SD) length of the retrohepatic vena cava is 78.21 (9.83) mm, which shows
      correlations with the patient's age and weight (r = -0.343 and 0.271,
      respectively, p < 0.05). An equation is obtained as follows: retrohepatic vena
      cava (millimeter) = 71.23 - 0.293 * age (year) + 0.32 * weight (kilogram). The
      shunt diameters must be 10 mm and 12 mm to maintain the blood pressure difference
      Point a and Point b at approximately 3.75 mm Hg (5 cm H2O), when the flow rate is
      3,000 mL/min and 5,000 mL/min, respectively. The stent graft showed effective
      hemostasis in tests. However, it failed when the inferior vena cava was pulled
      harder. CONCLUSION: A temporary stent graft as a new shunt for JHC injury has not
      been previously reported. It is a combination of both a traditional operation and
      a simple endovascular technique, which showed effective hemostasis in tests.

PMID- 25058265
TI  - Venous injuries in pediatric trauma: Systematic review of injuries and
      management.
AB  - BACKGROUND: Diagnosis of vascular injury in pediatric trauma is challenging as
      clinical signs may be masked by physiologic compensation. We aimed to (1)
      investigate the prevalence of noniatrogenic pediatric venous injuries, (2)
      discuss options in management of traumatic venous injury, and (3) investigate
      mortality from venous injury in pediatric trauma. Our objective was to provide
      the practicing clinician with a summary of the published literature and to
      develop an evidence-based guide to the diagnosis and management of traumatic
      venous injuries in children. METHODS: A systematic review of published literature
      (PubMed) describing noniatrogenic traumatic venous injury in the pediatric
      population (<17 years) was performed according to PRISMA [Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses] guidelines. Data were retrieved
      systematically under the following headings: Study Design, Population
      Demographics (dates of recruitment, mean age, mechanism of injury), Diagnostic
      Approach, Vessel Injured, Management (operative technique), and Mortality.
      RESULTS: Thirteen articles were included in this systematic review. In total, 508
      noniatrogenic traumatic venous injuries were reported in children between the
      year 1957 and present day. Mechanisms of injury included blunt trauma from seat
      belt-related injury and fall from height or penetrating trauma from gunshot and
      foreign object. Injury to the inferior vena cava was most frequently reported,
      followed by femoral vein and internal jugular injuries. Primary repair was the
      most frequently reported technique for surgical repair (38%), followed by
      ligation (25%) and end-to-end anastomosis (15%). Mortality in pediatric trauma
      patients who had venous injury was reported as 0% to 67% in published series,
      highest in the series in which the most frequently reported injury was of the
      inferior vena cava. CONCLUSION: Traumatic venous injury in the pediatric
      population is uncommon but may be associated with significant morbidity and
      mortality. Intra-abdominal venous injuries are associated with high mortality
      from exsanguination. Early diagnosis and intervention are therefore essential in
      such cases. LEVEL OF EVIDENCE: Systematic review, level IV.

PMID- 25058266
TI  - Maintaining comfort, cognitive function, and mobility in surgical intensive care
      unit patients.

PMID- 25058267
TI  - Peritoneal lactate as a potential biomarker for predicting the need for
      reintervention after abdominal surgery.
AB  - BACKGROUND: Early diagnosis of complications after abdominal surgery is crucial
      to improve outcomes. This study aimed to evaluate the use of the peritoneal-serum
      lactate ratio and of peritoneal lactate levels applied alone for predicting the
      need for reintervention after abdominal surgery. METHODS: This prospective
      observational study included 88 patients who underwent abdominal surgery (48
      emergency and 40 elective operations) and presented with fever, leukocytosis,
      late passage of flatus, and abdominal pain by the fourth postoperative day. The
      lactate levels were measured in the serum and peritoneal fluid. In total, 31 of
      88 patients required reintervention. The receiver operator characteristic
      analysis was used to determine the best threshold value for the peritoneal-serum
      lactate ratio and for peritoneal lactate levels applied alone to identify
      patients who required reintervention. RESULTS: A peritoneal-serum lactate ratio
      greater than 4.5 (area under the curve, 0.865; 95% confidence interval, 0.773
      0.957; p < 0.001) and a peritoneal lactate value greater than 9.1 mmol/L (area
      under the curve, 0.834; 95% confidence interval, 0.735-0.934; p < 0.0001)
      discriminated between patients who required reintervention with a sensitivity of
      91.3%, a specificity of 81%, and a negative predictive value of 94.4% and a
      sensitivity of 81.9%, a specificity of 82%, and a positive predictive value of
      89%, respectively. CONCLUSION: The results of our study support the hypothesis
      that the peritoneal-serum lactate ratio and the peritoneal lactate level applied
      alone could be safe, simple, inexpensive, noninvasive, and potentially valuable
      tools for the early identification of patients who require reintervention after
      elective or emergency abdominal surgery. LEVEL OF EVIDENCE: Diagnostic study,
      level III. Prognostic study, level III.

PMID- 25058268
TI  - The impact of arterial vessel injuries associated with pediatric supracondylar
      humeral fractures.
AB  - BACKGROUND: Pediatric supracondylar humeral fractures are regularly complicated
      by vascular compromise. However, the treatment regimen for pulseless hands with
      good capillary refill time is discussed controversially. The aim of the present
      study was to present our treatment strategy in a series of children sustaining
      supracondylar humeral fractures associated with impaired peripheral blood flow.
      METHODS: Medical charts of all children sustaining supracondylar humeral
      fractures treated between 1995 and 2009 were reviewed. Treatment and the course
      of patients with impaired peripheral blood flow were evaluated. Patients were
      invited for a follow-up examination. RESULTS: Forty of 499 patients sustaining a
      supracondylar humeral fracture presented with peripheral pulselessness. Two
      children underwent immediate vascular surgery. In the remaining 38 patients, the
      fracture was reduced, followed by a re-evaluation of the peripheral circulation.
      Twenty-four of those patients had normal peripheral pulse and capillary refill
      time, and no further therapy was necessary. Fourteen patients had a persisting
      absent peripheral pulse after fracture reduction. While in 4 of those patients
      including 3 patients with prolonged peripheral capillary refill time-vascular
      surgery was performed, 10 patients were successfully treated with "watchful
      waiting." At follow-up of 3.5 years (range, 2-6 years), the performed diagnostic
      workup including capillary refill time and blood pressure was without pathologic
      findings in all patients. CONCLUSION: Our data suggest that blood flow often
      recovers following reduction of supracondylar fractures with impaired peripheral
      vascularization. In cases of a "pink pulseless hand" (absent peripheral pulse and
      good peripheral capillary refill time), "watchful waiting" instead of immediate
      surgical exploration might be a treatment option. However, further studies with
      more patients have to be conducted to formulate a recommendation for the
      treatment of these severe injuries. LEVEL OF EVIDENCE: Therapeutic study, level
      V.

PMID- 25058269
TI  - Paroxysmal sympathetic hyperactivity, traumatic brain injury, and beta-blockers.

PMID- 25058270
TI  - Re: Paroxysmal sympathetic hyperactivity, traumatic brain injury, and beta
      blockers: Not all drugs are created equal.

PMID- 25058273
TI  - Underwater trauma causes a long-term specific increase in the expression of
      cyclooxygenase-2 in the ventral CA1 of the hippocampus.
AB  - The pro-inflammatory enzyme cyclooxygenase-2 (COX-2) is regularly expressed in
      the hippocampal neurons, but its role in emotional trauma is not known. Here we
      show that a single acute stress caused by a near-drowning experience results in
      heightened anxiety-like behavior one month after the trauma. Biochemical analyses
      of dorsal and ventral hippocampal CA1, CA3 and dentate gyrus revealed decreased
      ubiquitination and elevated levels of COX-2 in the traumatized animals only in
      the ventral CA1. To reveal the identity of the ubiquitin E3 ligase that targets
      COX-2, we tested the effect of several representative E3 ligases on COX-2
      expression in vitro. We found that while AIP4 and Nedd4 had no effect, Mdm2
      lowered COX-2 expression by nearly 50%, an effect that was not observed by its
      dominant negative form. To test whether this also occurs in the hippocampus, we
      immunoprecipitated Mdm2 from dorsal and ventral CA1 of traumatized and control
      animals and probed for the presence of COX-2. Our results showed that the levels
      of Mdm2 were not affected by the trauma but there was significantly less COX-2
      associated with Mdm2 in the ventral but not dorsal CA1 of the traumatized
      animals. Together these data propose that an increase in COX-2 expression in
      ventral CA1 following trauma is likely due to its attenuated degradation.
      Unraveling the pathways and mechanisms that control hippocampal COX-2 degradation
      is important to boost the development of novel therapeutic approaches designed to
      treat stress-related pathologies. 

PMID- 25058274
TI  - Experimental verification of fracture mechanism for polymer gels with controlled
      network structure.
AB  - Recently, polymer gels have drawn much attention as scaffolds for regenerative
      medicines, soft actuators, and functional membranes. These applications need
      tough and robust polymer gels as represented by the double network gels. To fully
      understand this mechanism and develop further advanced polymer gels, we need to
      fully understand the molecular origin of fracture energy for conventional polymer
      gels, which is inhibited by the inherent heterogeneity. In this paper, we show
      the experimental results on the fracture of model polymer gels with controlled
      network structure, and discuss the mechanism of the fracture of polymer gels. 

PMID- 25058276
TI  - The sensory ecology of nonconsumptive predator effects.
AB  - Nonconsumptive effects (NCEs) have been shown to occur in numerous systems and
      are regarded as important mechanisms by which predation structures natural
      communities. Sensory ecology-that is, the processes governing the production,
      propagation, and masking of cues by ambient noise-provides insights into the
      strength of NCEs as functions of the environment and modes of information
      transfer. We discuss how properties of predators are used by prey to encode
      threat, how the environment affects cue propagation, and the role of single
      sensory processes versus multimodal sensory processes. We discuss why the present
      body of literature documents the potential for strong NCEs but does not allow us
      to easily determine how this potential is expressed in nature or what factors or
      environments produce strong versus weak NCEs. Many of these difficulties stem
      from a body of literature in which certain sensory environments and modalities
      may be disproportionately represented and in which experimental methodologies are
      designed to show the existence of NCEs. We present a general framework for
      examining NCEs to identify the factors controlling the number of prey that
      respond to predator cues and discuss how the properties of predators, prey, and
      the environment may determine prey perceptive range and the duration and
      frequency of cue production. We suggest how understanding these relationships
      provides a schema for determining where, when, why, and how NCEs are important in
      producing direct and cascading effects in natural communities.

PMID- 25058275
TI  - Reconstituting ring-rafts in bud-mimicking topography of model membranes.
AB  - During vesicular trafficking and release of enveloped viruses, the budding and
      fission processes dynamically remodel the donor cell membrane in a protein- or a
      lipid-mediated manner. In all cases, in addition to the generation or relief of
      the curvature stress, the buds recruit specific lipids and proteins from the
      donor membrane through restricted diffusion for the development of a ring-type
      raft domain of closed topology. Here, by reconstituting the bud topography in a
      model membrane, we demonstrate the preferential localization of cholesterol- and
      sphingomyelin-enriched microdomains in the collar band of the bud-neck interfaced
      with the donor membrane. The geometrical approach to the recapitulation of the
      dynamic membrane reorganization, resulting from the local radii of curvatures
      from nanometre-to-micrometre scales, offers important clues for understanding the
      active roles of the bud topography in the sorting and migration machinery of key
      signalling proteins involved in membrane budding. 

PMID- 25058277
TI  - Multidimensional (co)evolutionary stability.
AB  - The complexity of biotic and abiotic environmental conditions is such that the
      fitness of individuals is likely to depend on multiple traits. Using a synthetic
      framework of phenotypic evolution that draws from adaptive dynamics and
      quantitative genetics approaches, we explore how the number of traits under
      selection influences convergence stability and evolutionary stability in models
      for coevolution in multidimensional phenotype spaces. Our results allow us to
      identify three different effects of trait dimensionality on stability. First are
      (i) a "combinatorial effect": without epistasis and genetic correlations, a
      higher number of trait dimensions offers more opportunities for equilibria to be
      unstable; and (ii) epistatic interactions, that is, fitness interactions between
      traits, which tend to destabilize evolutionary equilibria; this effect increases
      with the dimension of phenotype space. These first two effects influence both
      convergence stability and evolutionary stability, while (iii) genetic
      correlations (due, e.g., to pleiotropy or linkage disequilibrium) can affect only
      convergence stability. We illustrate the general prediction that increased
      dimensionality destabilizes evolutionary equilibria using examples drawn from
      well-studied classical models of frequency-dependent competition for resources,
      adaptation to a spatially heterogeneous environment, and antagonistic
      coevolution. In addition, our analyses show that increased dimensionality can
      favor diversification, for example, in the form of local adaptation, as well as
      evolutionary escape.

PMID- 25058278
TI  - Why is living fast dangerous? Disentangling the roles of resistance and tolerance
      of disease.
AB  - Primary axes of host developmental tempo (HDT; e.g., slow-quick return continuum)
      represent latent biological processes and are increasingly used to a priori
      identify hosts that contribute disproportionately more to pathogen transmission.
      The influence of HDT on host contributions to transmission depends on how HDT
      influences both resistance and tolerance of disease. Here, we use structural
      equation modeling to address known limitations of conventional measures of
      resistance and tolerance. We first provide a general resistance-tolerance
      metamodel from which system-specific models can be derived. We then develop a
      model specific to a group of vector-transmitted viruses that infect hundreds of
      grass species worldwide. We tested the model using experimental inoculations of
      six phylogenetically paired grass species. We found that (1) host traits covaried
      according to a prominent HDT axis, the slow-quick continuum; (2) infection caused
      a greater reduction in the performance of quick returns, with >80% of that
      greater impact explained by lesser resistance; (3) resistance-tolerance trade-off
      did not occur; and (4) phylogenetic control was necessary to measure the slow
      quick continuum, resistance, and tolerance. These results support the conclusion
      that HDT's main influence on host contributions to transmission is via
      resistance. More broadly, this study provides a framework for quantifying HDT's
      influence on host contributions to transmission.

PMID- 25058279
TI  - Frequency-dependent and correlational selection pressures have conflicting
      consequences for assortative mating in a color-polymorphic lizard, Uta
      stansburiana.
AB  - Genetically determined polymorphisms incorporating multiple traits can persist in
      nature under chronic, fluctuating, and sometimes conflicting selection pressures.
      Balancing selection among morphs preserves equilibrium frequencies, while
      correlational selection maintains favorable trait combinations within each morph.
      Under negative frequency-dependent selection, females should mate (often
      disassortatively) with rare male morphotypes to produce conditionally fit
      offspring. Conversely, under correlational selection, females should mate
      assortatively to preserve coadapted gene complexes and avoid ontogenetic
      conflict. Using controlled breeding designs, we evaluated consequences of
      assortative mating patterns in color-polymorphic side-blotched lizards (Uta
      stansburiana), to identify conflict between these sources of selection. Females
      who mated disassortatively, and to conditionally high-quality males in the
      context of frequency-dependent selection, experienced highest fertility rates. In
      contrast, assortatively mated females experienced higher fetal viability rates.
      The trade-off between fertility and egg viability resulted in no overall fitness
      benefit to either assortative or disassortative mating patterns. These results
      suggest that ongoing conflict between correlational and frequency dependent
      selection in polymorphic populations may generate a trade-off between rare-morph
      advantage and phenotypic integration and between assortative and disassortative
      mating decisions. More generally, interactions among multiple sources of
      diversity-promoting selection can alter adaptations and dynamics predicted to
      arise under any of these regimes alone.

PMID- 25058280
TI  - High food abundance permits the evolution of placentotrophy: evidence from a
      placental lizard, Pseudemoia entrecasteauxii.
AB  - Mechanisms of reproductive allocation are major determinants of fitness because
      embryos cannot complete development without receiving sufficient nutrition from
      their parents. The nourishment of offspring via placentas (placentotrophy) has
      evolved repeatedly in vertebrates, including multiple times in squamate reptiles
      (lizards and snakes). Placentotrophy has been suggested to evolve only if food is
      sufficiently abundant throughout gestation to allow successful embryogenesis. If
      scarcity of food prevents successful embryogenesis, females should recoup
      nutrients allocated to embryos via abortion, reabsorption, and/or cannibalism. We
      tested these hypotheses in the placentotrophic southern grass skink Pseudemoia
      entrecasteauxii. We fed females one of four diets (high constant, high variable,
      low constant, and low variable) during gestation and tested the effects of both
      food amount and schedule of feeding on developmental success, cannibalism rate,
      placental nutrient transport, offspring size, and maternal growth and body
      condition. Low food availability reduced developmental success, placental
      nutrient transport, offspring size, and maternal growth and body condition.
      Cannibalism of offspring also increased when food was scarce. Schedule of feeding
      did not affect offspring or mothers. We suggest that high food abundance and
      ability to abort and cannibalize poor-quality offspring are permissive factors
      necessary for placentotrophy to be a viable strategy of reproductive allocation.

PMID- 25058281
TI  - Taxonomic, phylogenetic, and trait Beta diversity in South American hummingbirds.
AB  - Comparison of the taxonomic, phylogenetic, and trait dimensions of beta diversity
      may uncover the mechanisms that generate and maintain biodiversity, such as
      geographic isolation, environmental filtering, and convergent adaptation. We
      developed an approach to predict the relationship between environmental and
      geographic distance and the dimensions of beta diversity. We tested these
      predictions using hummingbird assemblages in the northern Andes. We expected
      taxonomic beta diversity to result from recent geographic barriers limiting
      dispersal, and we found that cost distance, which includes barriers, was a better
      predictor than Euclidean distance. We expected phylogenetic beta diversity to
      result from historical connectivity and found that differences in elevation were
      the best predictors of phylogenetic beta diversity. We expected high trait beta
      diversity to result from local adaptation to differing environments and found
      that differences in elevation were correlated with trait beta diversity. When
      combining beta diversity dimensions, we observe that high beta diversity in all
      dimensions results from adaption to different environments between isolated
      assemblages. Comparisons with high taxonomic, low phylogenetic, and low trait
      beta diversity occurred among lowland assemblages separated by the Andes,
      suggesting that geographic barriers have recently isolated lineages in similar
      environments. We provide insight into mechanisms governing hummingbird
      biodiversity patterns and provide a framework that is broadly applicable to other
      taxonomic groups.

PMID- 25058282
TI  - Assortative mating and the maintenance of population structure in a natural
      hybrid zone.
AB  - Understanding the factors that give rise to natural hybrid zones and govern their
      dynamics and structure is important to predicting the evolutionary consequences
      of hybridization. Here we use a combination of multigenerational population
      genetic data, mating patterns from a natural population, behavioral assays, and
      mark-recapture data within clinal hybrid zones of the genus Xiphophorus to test
      the role of assortative mating in maintaining population structure and the
      potential for ongoing genetic exchange between heterospecifics. Our data
      demonstrate that population structure is temporally robust and driven largely by
      assortative mating stemming from precopulatory isolation between pure species.
      Furthermore, mark-recapture data revealed that rates of migration within the same
      stream reach are far below the level needed to support population structure. In
      contrast to many empirical studies of natural hybrid zones, there appeared to be
      no hybrid male dysfunction or discrimination against hybrid males by pure
      parental females, and hybrid females mated and associated with pure species and
      hybrid males at random. Despite strong isolation between pure parentals, hybrids
      therefore can act as a conduit for genetic exchange between heterospecifics,
      which has been shown to increase the tempo of evolutionary change. Additionally,
      our findings highlight the complexity of natural hybrid zone dynamics,
      demonstrating that sexual and ecological selection together can give rise to
      patterns that do not fit classical models of hybrid zone evolution.

PMID- 25058283
TI  - Increasing energetic cost of biosynthesis during growth makes refeeding
      deleterious.
AB  - Diet restriction (DR) enhances animals' health maintenance, but refeeding
      reverses its beneficial effects. However, to what degree refeeding reverses the
      beneficial effects of DR remains controversial. Here, I develop a theoretical
      model for reconciling the results of refeeding studies and understanding the
      dynamic and reversible mechanism underlying the effects of diet on health from
      the energetic viewpoint. By illustrating the negative correlation between health
      maintenance and the energetic cost of growth in animals under different diet
      regimes, the model explains why, in some cases, refed animals have better health
      and live longer than freely fed controls. More importantly, the model reveals
      that, in some species, the energetic cost of synthesizing biomass increases
      during growth, so the expensive compensatory growth induced by refeeding later in
      life offsets the benefits of the inexpensive retarded growth induced by diet
      restriction early in life. Thus, in these species, refeeding drives animals to
      allocate more energy to growth and less to maintenance and therefore leads to
      poor health status and shorter life span compared to freely fed controls.

PMID- 25058284
TI  - Initial invasion of gametophytic self-incompatibility alleles in the absence of
      tight linkage between pollen and pistil S alleles.
AB  - In homomorphic self-incompatibility (SI) systems of plants, the loci controlling
      the pollen and pistil types are tightly linked, and this prevents the generation
      of compatible combinations of alleles expressing pollen and pistil types, which
      would result in self-fertilization. We modeled the initial invasion of the first
      pollen and pistil alleles in gametophytic SI to determine whether these alleles
      can stably coexist in a population without tight linkage. We assume pollen and
      pistil loci each carry an incompatibility allele S and an allele without an
      incompatibility function N. We assume that pollen with an S allele are
      incompatible with pistils carrying S alleles, whereas other crosses are
      compatible. Ovules in pistils carrying an S allele suffer viability costs because
      recognition consumes resources. We found that the cost of carrying a pistil S
      allele allows pollen and pistil S alleles to coexist in a stable equilibrium if
      linkage is partial. This occurs because parents that carry pistil S alleles but
      are homozygous for pollen N alleles cannot avoid self-fertilization; however,
      they suffer viability costs. Hence, pollen N alleles are selected again. When
      pollen and pistil S alleles can coexist in a polymorphic equilibrium, selection
      will favor tighter linkage.

PMID- 25058285
TI  - Does urbanization promote floral diversification? Implications from changes in
      herkogamy with pollinator availability in an urban-rural area.
AB  - Although land-use changes such as urbanization have dramatically altered plant
      pollinator interactions, little is known about their effects on pollen limitation
      and floral traits. In this study, we examined pollinator visit frequency,
      reproductive success, and floral trait measurements in 12 populations of the
      annual andromonoecious Commelina communis in an urban-rural area. Pollinator and
      mate availability decreased significantly with developed land area around the
      study site. Most urbanized populations suffered from significant pollinator
      limited male and/or female reproductive success. High fruit set in urbanized
      populations may suggest the presence of high reproductive assurance by selfing.
      The stigma height and degree of herkogamy significantly decreased with increased
      pollinator limitation. Petal length, anther height, and/or the pollen:ovule ratio
      tended to be low in pollinator- and mate-limited urban populations. One urban
      population with high pollinator availability had flowers with higher herkogamy
      and stigma height compared to rural populations. These results suggest that
      urbanization may provide diverse selective forces that could affect the
      phenotypic variation in floral traits.

PMID- 25058286
TI  - Reconciling diversification: random pulse models of speciation and extinction.
AB  - Inferring the underlying speciation-extinction dynamics of a clade from the
      phylogenetic relationships of contemporary species has proven difficult,
      primarily because the record of extinction is absent. Moreover, models of
      diversification tend to emphasize either time homogeneity or gradual trends in
      speciation and extinction rates. In contrast, the fossil records of many groups
      exhibit repeated increase and decrease of species richness within clades.
      Modeling this dynamic in the structure of phylogenetic trees has had limited
      application. Here, I consider the idea that pulses of diversification followed by
      declines in clade size-such pulses having short life spans in evolutionary time
      occur frequently and more or less randomly among lineages. I suggest that this
      model might characterize diversification quite generally. Analyses of a recent
      phylogeny of the ovenbirds and treecreepers (Aves: Furnariidae) supports the
      random pulse model in that ancestral lineages at 15, 10, and 5 Ma exhibit
      diversification rate heterogeneity, but the sizes of ancestral and descendant
      lineages are uncorrelated. Simulations of such a process and its manifestations
      in reconstructed phylogenies would help to characterize diversification pulses in
      an abstract sense and draw attention to the underlying biological processes that
      produce them.

PMID- 25058287
TI  - Rethinking niche evolution: experiments with natural communities of Protozoa in
      pitcher plants.
AB  - Classic niche theory predicts that competing species will evolve to use different
      resources and interact less, whereas recent niche-converge ideas predict that
      species evolve to use similar resources and interact more. Most data supporting
      niche evolution are based on observations of contemporary niche use, whereas
      experimental support is quite sparse. We followed the evolution of four species
      of Protozoa during succession in the water-filled leaves of the pitcher plant,
      Sarracenia purpurea, and found that evolution in multispecies systems follows a
      surprising pattern. Over several hundred generations, weak competitors evolved to
      be stronger, while strong competitors evolved to become weaker, which does not
      conform to expectations of either niche divergence or convergence. Evolution in
      this system appears to occur in response to characteristics of a suite of several
      competitors in the community, rather than pairwise interactions. Ecologists may
      need to rethink the roles of competition and evolution in structuring
      communities.

PMID- 25058289
TI  - Response diversity can increase ecological resilience to disturbance in coral
      reefs.
AB  - Community-level resilience depends on the interaction between multiple
      populations that vary in individual responses to disturbance. For example, in
      tropical reefs, some corals can survive higher stress (resistance) while others
      exhibit faster recovery (engineering resilience) following disturbances such as
      thermal stress. While each type will negatively affect the other through
      competition, each might also benefit the other by reducing the potential for an
      additional competitor such as macroalgae to invade after a disturbance. To
      determine how community composition affects ecological resilience, we modeled
      coral-macroalgae interactions given either a resistant coral, a resilient coral,
      or both together. Having both coral types (i.e., response diversity) can lead to
      observable enhanced ecological resilience if (1) the resilient coral is not a
      superior competitor and (2) disturbance levels are high enough such that the
      resilient coral would collapse when considered alone. This enhanced resilience
      occurs through competitor-enabled rescue where each coral increases the potential
      for the other to recover from disturbance through external recruitment, such that
      both corals benefit from the presence of each other in terms of total cover and
      resilience. Therefore, conservation management aimed at protecting resilience
      under global change requires consideration of both diversity and connectivity
      between sites experiencing differential disturbance.

PMID- 25058290
TI  - Local gamete competition explains sex allocation and fertilization strategies in
      the sea.
AB  - Within and across taxa, there is much variation in the mode of fertilization,
      that is, whether eggs and/or sperm are released or kept inside or on the surface
      of the parent's body. Although the evolutionary consequences of fertilization
      mode are far-reaching, transitions in the fertilization mode itself have largely
      escaped theoretical attention. Here we develop the first evolutionary model of
      egg retention and release, which also considers transitions between
      hermaphroditism and dioecy as well as egg size evolution. We provide a unifying
      explanation for reported associations between small body size, hermaphroditism,
      and egg retention in marine invertebrates that have puzzled researchers for more
      than 3 decades. Our model, by including sperm limitation, shows that all these
      patterns can arise as an evolutionary response to local competition between eggs
      for fertilization. This can provide a general explanation for three empirical
      patterns: sperm casters tend to be smaller than related broadcast spawners,
      hermaphroditism is disproportionately common in sperm casters, and offspring of
      sperm casters are larger. Local gamete competition also explains a universal
      sexual asymmetry: females of some species retain their gametes while males
      release theirs, but the opposite ("egg casting") lacks evolutionary stability and
      is apparently not found in nature.

PMID- 25058291
TI  - Bringing the male side of plant sex into focus.

PMID- 25058292
TI  - Functional display of triphenylmethane reductase for dye removal on the surface
      of Escherichia coli using N-terminal domain of ice nucleation protein.
AB  - Traditional biological treatment for triphenylmethane dye effluent is stuck with
      the inaccessibility of dye molecules to intracellular dye-degrading enzyme, thus
      a high-efficiency and low-cost method for dye decolorization is highly desirable.
      Here we established a bioremediation approach to display triphenylmethane
      reductase (TMR) on the surface of Escherichia coli (E. coli) using N-terminal of
      ice nucleation protein as anchoring motif for triphenylmethane dye decolorization
      for the first time. Approximately 85% of recombinant protein positioning on the
      surface of E. coil cells exhibited high activity and stability. The optimal
      temperature and pH of the surface-displayed TMR are 50  degrees C and 8.5,
      respectively. Comparing with other reported microorganisms, the decolorization
      rate for malachite green of this engineered strain is the highest so far,
      reaching 640 MUmol min(-1) g(-1) dry weight cells. These results indicate that
      this engineered E. coli strain is a very promising candidate for synthetic dye
      removal.

PMID- 25058293
TI  - Catalytic pyrolysis of miscanthus * giganteus in a spouted bed reactor.
AB  - A conical spouted bed reactor was designed and tested for fast catalytic
      pyrolysis of miscanthus * giganteus over Zeolite Socony Mobil-5 (ZSM-5) catalyst,
      in the temperature range of 400-600  degrees C and catalyst to biomass ratios 1:1
      5:1. The effect of operating conditions on the lumped product distribution, bio
      oil selectivity and gas composition was investigated. In particular, it was shown
      that higher temperature favors the production of gas and bio-oil aromatics and
      results in lower solid and liquid yields. Higher catalyst to biomass ratios
      increased the gas yield, at the expense of liquid and solid products, while
      enhancing aromatic selectivity. The separate catalytic effects of ZSM-5 catalyst
      and its Al2O3 support were studied. The support contributes to increased
      coke/char formation, due to the uncontrolled spatial distribution and activity of
      its alumina sites. The presence of ZSM-5 zeolite in the catalyst enhanced the
      production of aromatics due to its proper pore size distribution and activity.

PMID- 25058294
TI  - Extraction of saponifiable lipids from wet microalgal biomass for biodiesel
      production.
AB  - Saponifiable lipids (SLs) were extracted with hexane from wet biomass (86 wt%
      water) of the microalga Nannochloropsis gaditana in order to transform them into
      fatty acid methyl esters (FAMEs, biodiesel). The influence of homogenization
      pressure on SL extraction yield at low temperature (20-22  degrees C) was
      studied. Homogenization at 1700 bar tripled the SL extraction yield. Two biomass
      batches with similar total lipid content but different lipidic compositions were
      used. Batch 1 contained fewer SLs (12.0 wt%) and neutral saponifiable lipids
      (NSLs, 7.9 wt%) than batch 2 (21.6 and 17.2 wt%, respectively). For this reason,
      and due to the selectivity of hexane toward NSLs, high SL yield (69.1 wt%) and
      purity (71.0 wt%) were obtained from batch 2. Moreover, this extract contains a
      small percentage of polyunsaturated fatty acids (16.9 wt%), thereby improving the
      biodiesel quality. Finally, up to 97.0% of extracted SLs were transformed to
      FAMEs by acid catalyzed transesterification.

PMID- 25058295
TI  - Pulp properties resulting from different pretreatments of wheat straw and their
      influence on enzymatic hydrolysis rate.
AB  - Wheat straw was subjected to three different processes prior to saccharification,
      namely alkaline pulping, natural pulping and autohydrolysis, in order to study
      their effect on the rate of enzymatic hydrolysis. Parameters like medium
      concentration, temperature and time have been varied in order to optimize each
      method. Milling the raw material to a length of 4mm beforehand showed the best
      cost-value-ratio compared to other grinding methods studied. Before
      saccharification the pulp can be stored in dried form, leading to a high yield of
      glucose. Furthermore the relation of pulp properties (i.e. intrinsic viscosity,
      Klason-lignin and hemicelluloses content, crystallinity, morphology) to cellulose
      hydrolysis is discussed. 

PMID- 25058296
TI  - Membrane fouling in a submerged membrane bioreactor with focus on surface
      properties and interactions of cake sludge and bulk sludge.
AB  - In this study, the fouling behaviors and surface properties of cake sludge and
      bulk sludge in a submerged membrane bioreactor (MBR) were investigated and
      compared. It was found that the specific filtration resistance (SFR) of cake
      sludge was about 5 times higher than that of bulk sludge. Two types of sludge
      possessed similar extracellular polymeric substances (EPS) content, particle size
      distribution (PSD) and zeta potential. However, their surface properties in terms
      of surface tensions were significantly different. Further analysis showed that
      cake sludge was more hydrophilic and had worse aggregation ability. Moreover,
      cake sludge surface possessed more hydrocarbon, less oxygen and nitrogen moieties
      than bulk sludge surface. It was suggested that, rather than EPS and PSD
      differences, the differences in the surface composition were the main cause of
      the great differences in SFR and adhesion ability between cake sludge and bulk
      sludge. 

PMID- 25058297
TI  - Synergistic effect on thermal behavior during co-pyrolysis of lignocellulosic
      biomass model components blend with bituminous coal.
AB  - Co-thermochemical conversion of lignocellulosic biomass and coal has been
      investigated as an effective way to reduce the carbon footprint. Successful
      evaluating on thermal behavior of the co-pyrolysis is prerequisite for predicting
      performance and optimizing efficiency of this process. In this paper, pyrolysis
      and kinetics characteristics of three kinds of lignocellulosic biomass model
      components (cellulose, hemicellulose, and lignin) blended with a kind of Chinese
      bituminous coal were explored by thermogravimetric analyzer and Kissinger-Akahira
      Sunose method. The results indicated that the addition of model compounds had
      different synergistic effects on thermal behavior of the bituminous coal. The
      cellulose showed positive synergistic effects on the thermal decomposition of the
      coal bituminous coal with lower char yield than calculated value. For
      hemicellulose and lignin, whether positive or negative synergistic was related to
      the mixed ratio and temperature range. The distribution of the average activation
      energy values for the mixtures showed nonadditivity performance. 

PMID- 25058298
TI  - A new method for rapid construction of a Pseudomonas sp. HF-1 bioaugmented
      system: accelerating acylated homoserine lactones secretion by pH regulation.
AB  - Pseudomonas sp. HF-1 bioaugmented systems were operated to treat tobacco
      wastewater under pH 5.5 for three cycles and pH 8.0 for the rest, which was
      suitable for HF-1 biofilm formation. The results showed that, under pH control,
      the contents of 3-oxo-C6-HSL, C6-HSL and 3-oxo-C8-HSL were significantly higher
      than HF-1 thresholds for biofilm formation. Compared with non-pH controlled
      reactors, HF-1 showed greater colonization in pH controlled reactors, primarily
      owing to the high extracellular polymeric substances secretion induced by quorum
      sensing. Accordingly, high indigenous community activity and granular sludge were
      observed. Sludge granulation occurred from the seventh cycle, and the average
      diameter was greater than 400 MUm. These systems were also highly efficient with
      nearly 100% nicotine degradation and 60% total organic carbon removal. Overall,
      the results indicate that pH regulation is a new and feasible method for
      acceleration of releasing of auto-inducers, which is beneficial to construction
      of HF-1 bioaugmented systems.

PMID- 25058299
TI  - Combined pretreatment using alkaline hydrothermal and ball milling to enhance
      enzymatic hydrolysis of oil palm mesocarp fiber.
AB  - Hydrothermal pretreatment of oil palm mesocarp fiber was conducted in tube
      reactor at treatment severity ranges of log Ro = 3.66-4.83 and partial removal of
      hemicellulose with migration of lignin was obtained. Concerning maximal recovery
      of glucose and xylose, 1.5% NaOH was impregnated in the system and subsequent
      ball milling treatment was employed to improve the conversion yield. The effects
      of combined hydrothermal and ball milling pretreatments were evaluated by
      chemical composition changes by using FT-IR, WAXD and morphological alterations
      by SEM. The successful of pretreatments were assessed by the degree of enzymatic
      digestibility of treated samples. The highest xylose and glucose yields obtained
      were 63.2% and 97.3% respectively at cellulase loadings of 10 FPU/g-substrate
      which is the highest conversion from OPMF ever reported.

PMID- 25058300
TI  - The stability of aerobic granular sludge treating municipal sludge deep
      dewatering filtrate in a bench scale sequencing batch reactor.
AB  - Inoculated with mature aerobic granular sludge in a sequencing batch reactor,
      gradually increasing the proportion of municipal sludge deep dewatering filtrate
      in influent, aerobic granular sludge was domesticated after 84 days and
      maintained its structure during the operation. The domesticated AGS was yellowish
      brown, dense and irregular spherical shape, average size was 1.49 mm, water
      content and specific density were 98.13% and 1.0114, the SVI and settling
      velocity were 40 ml/g and 46.5m/h. After 38 days, NO3(-)-N accumulated obviously
      in the reactor as lack of carbon sources. When adding 1-3g solid CH3COONa at 4.5
      and 5.5h of each cycle from the 57th day, the removal rate of TN rose to above
      90% after 20 days, where effective COD removal and denitrification were realized
      in a single bioreactor. Finally, the removal rates of COD, TP, TN and NH4(+)-N
      were higher than 95%, 88%, 96% and 99%.

PMID- 25058301
TI  - Efficient production of acetone-butanol-ethanol (ABE) from cassava by a
      fermentation-pervaporation coupled process.
AB  - Production of acetone-butanol-ethanol (ABE) from cassava was investigated with a
      fermentation-pervaporation (PV) coupled process. ABE products were in situ
      removed from fermentation broth to alleviate the toxicity of solvent to the
      Clostridium acetobutylicum DP217. Compared to the batch fermentation without PV,
      glucose consumption rate and solvent productivity increased by 15% and 21%,
      respectively, in batch fermentation-PV coupled process, while in continuous
      fermentation-PV coupled process running for 304 h, the substrate consumption
      rate, solvent productivity and yield increased by 58%, 81% and 15%, reaching 2.02
      g/Lh, 0.76 g/Lh and 0.38 g/g, respectively. Silicalite-1 filled
      polydimethylsiloxane (PDMS)/polyacrylonitrile (PAN) membrane modules ensured
      media recycle without significant fouling, steadily generating a highly
      concentrated ABE solution containing 201.8 g/L ABE with 122.4 g/L butanol. After
      phase separation, a final product containing 574.3g/L ABE with 501.1g/L butanol
      was obtained. Therefore, the fermentation-PV coupled process has the potential to
      decrease the cost in ABE production.

PMID- 25058302
TI  - Thermal decomposition dynamics and severity of microalgae residues in
      torrefaction.
AB  - To figure out the torrefaction characteristics and weight loss dynamics of
      microalgae residues, the thermogravimetric analyses of two microalgae
      (Chlamydomonas sp. JSC4 and Chlorella sorokiniana CY1) residues are carried out.
      A parameter of torrefaction severity index (TSI) in the range of 0-1, in terms of
      weight loss ratio between a certain operation and a reference operation, is
      defined to indicate the degree of biomass thermal degradation due to
      torrefaction. The TSI profiles of the two residues are similar to each other;
      therefore, the parameter may be used to describe the torrefaction extents of
      various biomass materials. The curvature of TSI profile along light torrefaction
      is slight, elucidating its slight impact on biomass thermal degradation. The
      sharp curvature along severe torrefaction in the initial pretreatment period
      reveals that biomass upgraded with high temperature and short duration is more
      effective than using low temperature with long duration. 

PMID- 25058303
TI  - Loneliness, social relations and health and well-being in deprived communities.
AB  - There is a growing policy concern about the extent of loneliness in advanced
      societies, and its prevalence among various social groups. This study looks at
      loneliness among people living in deprived communities, where there may be
      additional barriers to social engagement including low incomes, fear of crime,
      poor services and transient populations. The aim was to examine the prevalence of
      loneliness, and also its associations with different types of social contacts and
      forms of social support, and its links to self-reported health and well-being in
      the population group. The method involved a cross-sectional survey of 4302 adults
      across 15 communities, with the data analysed using multinomial logistic
      regression controlling for sociodemographics, then for all other predictors
      within each domain of interest. Frequent feelings of loneliness were more common
      among those who: had contact with family monthly or less; had contact with
      neighbours weekly or less; rarely talked to people in the neighbourhood; and who
      had no available sources of practical or emotional support. Feelings of
      loneliness were most strongly associated with poor mental health, but were also
      associated with long-term problems of stress, anxiety and depression, and with
      low mental well-being, though to a lesser degree. The findings are consistent
      with a view that situational loneliness may be the product of residential
      structures and resources in deprived areas. The findings also show that
      neighbourly behaviours of different kinds are important for protecting against
      loneliness in deprived communities. Familiarity within the neighbourhood, as
      active acquaintance rather than merely recognition, is also important. The
      findings are indicative of several mechanisms that may link loneliness to health
      and well-being in our study group: loneliness itself as a stressor; lonely people
      not responding well to the many other stressors in deprived areas; and loneliness
      as the product of weak social buffering to protect against stressors. 

PMID- 25058305
TI  - Psychiatric misdiagnoses in Dandy-Walker variant.
AB  - Cases of intellectual impairment and aberrant behavior in patients with
      cerebellar diseases have been described since the early nineteenth century. Here,
      we report on a patient suffering from Dandy-Walker variant who presented with
      symptoms of obsessive compulsive disorder and delusional disorder. The current
      findings emphasize the potential relevance of focal cerebellar lesions as organic
      correlates of these disorders. 

PMID- 25058304
TI  - Engineered biosynthesis of bacteriochlorophyll b in Rhodobacter sphaeroides.
AB  - Bacteriochlorophyll b has the most red-shifted absorbance maximum of all
      naturally occurring photopigments. It has a characteristic ethylidene group at
      the C8 position in place of the more common ethyl group, the product of a C8
      vinyl reductase, which is carried by the majority of chlorophylls and
      bacteriochlorophylls used in photosynthesis. The subsequent and first step
      exclusive to bacteriochlorophyll biosynthesis, the reduction of the C7=C8 bond,
      is catalyzed by chlorophyllide oxidoreductase. It has been demonstrated that the
      enzyme from bacteriochlorophyll a-utilizing bacteria can catalyze the formation
      of compounds carrying an ethyl group at C8 from both ethyl- and vinyl-carrying
      substrates, indicating a surprising additional C8-vinyl reductase function, while
      the enzyme from organisms producing BChl b could only catalyze C7=C8 reduction
      with a vinyl substrate, but this product carried an ethylidene group at the C8
      position. We have replaced the native chlorophyllide oxidoreductase-encoding
      genes of Rhodobacter sphaeroides with those from Blastochloris viridis, but the
      switch from bacteriochlorophyll a to b biosynthesis is only detected when the
      native conventional C8-vinyl reductase is absent. We propose a non-enzymatic
      mechanism for ethylidene group formation based on the absence of cellular C8
      vinyl reductase activity. 

PMID- 25058306
TI  - Metastasis of a cervical carcinoma to the clitoris.

PMID- 25058307
TI  - Low-intensity agricultural landscapes in Transylvania support high butterfly
      diversity: implications for conservation.
AB  - European farmland biodiversity is declining due to land use changes towards
      agricultural intensification or abandonment. Some Eastern European farming
      systems have sustained traditional forms of use, resulting in high levels of
      biodiversity. However, global markets and international policies now imply rapid
      and major changes to these systems. To effectively protect farmland biodiversity,
      understanding landscape features which underpin species diversity is crucial.
      Focusing on butterflies, we addressed this question for a cultural-historic
      landscape in Southern Transylvania, Romania. Following a natural experiment, we
      randomly selected 120 survey sites in farmland, 60 each in grassland and arable
      land. We surveyed butterfly species richness and abundance by walking transects
      with four repeats in summer 2012. We analysed species composition using Detrended
      Correspondence Analysis. We modelled species richness, richness of functional
      groups, and abundance of selected species in response to topography, woody
      vegetation cover and heterogeneity at three spatial scales, using generalised
      linear mixed effects models. Species composition widely overlapped in grassland
      and arable land. Composition changed along gradients of heterogeneity at local
      and context scales, and of woody vegetation cover at context and landscape
      scales. The effect of local heterogeneity on species richness was positive in
      arable land, but negative in grassland. Plant species richness, and structural
      and topographic conditions at multiple scales explained species richness,
      richness of functional groups and species abundances. Our study revealed high
      conservation value of both grassland and arable land in low-intensity Eastern
      European farmland. Besides grassland, also heterogeneous arable land provides
      important habitat for butterflies. While butterfly diversity in arable land
      benefits from heterogeneity by small-scale structures, grasslands should be
      protected from fragmentation to provide sufficiently large areas for butterflies.
      These findings have important implications for EU agricultural and conservation
      policy. Most importantly, conservation management needs to consider entire
      landscapes, and implement appropriate measures at multiple spatial scales. 

PMID- 25058309
TI  - A systematic review of amyloid-beta peptides as putative mediators of the
      association between affective disorders and Alzheimer's disease.
AB  - BACKGROUND: Affective disorders are associated with an increased occurrence of
      cognitive deficits and have been linked to cognitive impairment and Alzheimer's
      disease. The putative molecular mechanisms involved in these associations are
      however not clear. The aim of this systematic review was to explore clinically
      founded evidence for amyloid-beta peptides in cerebrospinal fluid and blood as
      putative biomarkers for affective disorders. METHOD: Systematic searches in
      Embase and PubMed databases yielded 23 eligible, observational studies. RESULTS:
      Despite inconsistencies that were partly ascribed to the application of different
      assay formats, study results indicate a potentially altered amyloid-beta
      metabolism in affective disorder. LIMITATIONS: Since most studies used a cross
      sectional design, causality is difficult to establish. Moreover, methodological
      rigor of included studies varied and several studies were limited by very low
      sample numbers. Finally, different assays for amyloid-beta were utilized in the
      different studies, thus hampering comparisons. CONCLUSION: To unravel possible
      risk relations and causalities between affective disorder and Alzheimer's disease
      and to determine how amyloid-beta concentrations change over time and are
      associated with cognition as well as affective symptomatology, future research
      should include prospective, longitudinal studies, implemented in large study
      populations, where peripheral and central amyloid-beta ratios are quantified
      concomitantly and continuously across various affective phases. Also, to enable
      inter-survey comparisons, the use of standardized pre-analytical/analytical
      procedures is crucial.

PMID- 25058308
TI  - Metagenomic identification of a novel salt tolerance gene from the human gut
      microbiome which encodes a membrane protein with homology to a brp/blh-family
      beta-carotene 15,15'-monooxygenase.
AB  - The human gut microbiome consists of at least 3 million non-redundant genes, 150
      times that of the core human genome. Herein, we report the identification and
      characterisation of a novel stress tolerance gene from the human gut metagenome.
      The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh
      family beta-carotene monooxygenase. Cloning and heterologous expression of brpA
      in Escherichia coli confers a significant salt tolerance phenotype. Furthermore,
      when cultured in the presence of exogenous beta-carotene, cell pellets adopt a
      red/orange pigmentation indicating the incorporation of carotenoids in the cell
      membrane. 

PMID- 25058310
TI  - PANET: a GPU-based tool for fast parallel analysis of robustness dynamics and
      feed-forward/feedback loop structures in large-scale biological networks.
AB  - It has been a challenge in systems biology to unravel relationships between
      structural properties and dynamic behaviors of biological networks. A Cytoscape
      plugin named NetDS was recently proposed to analyze the robustness-related
      dynamics and feed-forward/feedback loop structures of biological networks.
      Despite such a useful function, limitations on the network size that can be
      analyzed exist due to high computational costs. In addition, the plugin cannot
      verify an intrinsic property which can be induced by an observed result because
      it has no function to simulate the observation on a large number of random
      networks. To overcome these limitations, we have developed a novel software tool,
      PANET. First, the time-consuming parts of NetDS were redesigned to be processed
      in parallel using the OpenCL library. This approach utilizes the full computing
      power of multi-core central processing units and graphics processing units.
      Eventually, this made it possible to investigate a large-scale network such as a
      human signaling network with 1,609 nodes and 5,063 links. We also developed a new
      function to perform a batch-mode simulation where it generates a lot of random
      networks and conducts robustness calculations and feed-forward/feedback loop
      examinations of them. This helps us to determine if the findings in real
      biological networks are valid in arbitrary random networks or not. We tested our
      plugin in two case studies based on two large-scale signaling networks and found
      interesting results regarding relationships between coherently coupled feed
      forward/feedback loops and robustness. In addition, we verified whether or not
      those findings are consistently conserved in random networks through batch-mode
      simulations. Taken together, our plugin is expected to effectively investigate
      various relationships between dynamics and structural properties in large-scale
      networks. Our software tool, user manual and example datasets are freely
      available at http://panet-csc.sourceforge.net/. 

PMID- 25058311
TI  - High-rosmarinic acid spearmint tea in the management of knee osteoarthritis
      symptoms.
AB  - Individuals with medically diagnosed knee osteoarthritis (OA) participated in a
      randomized, double-blind study to investigate the effects of a high-rosmarinic
      acid (rosA) spearmint tea. Sixty-two participants were randomized by sex and
      screening pain score to consume tea brewed from a high-rosA spearmint variety or
      a commercially available spearmint twice daily for 16 weeks. Pain, quality of
      life (QoL), and physical function at baseline and week 16 were assessed using the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short
      Form 36-item Health Survey (SF-36), 6-minute walk test (6MWT), and stair climb
      test (SCT). Data from 46 participants (mean age=60.7; BMI=32.9 kg/m(2)) were
      analyzed. Pain score significantly decreased from week 0 to 16 for the high-rosA
      group but not for the control group and scores for stiffness and physical
      disability significantly decreased from week 0 to 16 for both groups. Increased
      QoL score on the bodily pain index in the SF-36 was observed at week 16 within
      the high-rosA group only, although no significant differences were observed
      between the groups. A nonsignificant improvement was observed in the 6MWT at week
      16 in the high-rosA group only. There were no changes in the SCT for either
      group. Therefore, 16-week daily consumption of the high-rosA and commercial
      spearmint teas significantly improved stiffness and physical disability scores in
      adults with knee OA, but only the high-rosA tea significantly decreased pain.
      Consumption of high-rosA tea warrants further consideration as a potential
      complementary therapy to reduce pain in OA. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT01380015.

PMID- 25058314
TI  - Vertical stiffness and muscle strain in professional Australian football.
AB  - Abstract The purpose of this study was to establish if vertical stiffness was
      greater in professional Australian rules footballers who sustained a lower limb
      skeletal muscle strain compared to those who did not, and to establish if a
      relationship between age, or training history, and vertical stiffness existed.
      Thirty-one participants underwent weekly rebound jump testing on a force platform
      over two seasons. Vertical stiffness was calculated for injured players and the
      uninjured cohort 1 and 3 weeks prior to sustaining an injury and at the end of
      preseason. Eighteen athletes were in the "uninjured" cohort and 13 in the
      "injured" cohort. No significant difference in vertical stiffness was observed
      between groups (P = 0.18 for absolute stiffness; P = 0.08 for stiffness relative
      to body mass), within groups (P = 0.83 and P = 0.88, respectively) or for a
      time*cohort interaction (P = 0.77 and P = 0.80, respectively). No relationship
      between age and vertical stiffness existed (r = -0.06 for absolute and relative
      stiffness), or training history and vertical stiffness (r = -0.01 and 0.00 for
      absolute and relative stiffness, respectively) existed. These results and others
      lend to suggest that vertical stiffness is not related to lower limb muscle
      strain injury.

PMID- 25058312
TI  - Dual blockade of the A1 and A2A adenosine receptor prevents amyloid beta toxicity
      in neuroblastoma cells exposed to aluminum chloride.
AB  - In a previous work we have shown that exposure to aluminum (Al) chloride (AlCl3)
      enhanced the neurotoxicity of the amyloid beta(25-35) fragment (Abeta(25-35)) in
      neuroblastoma cells and affected the expression of Alzheimer's disease (AD)
      related genes. Caffein, a compound endowed with beneficial effects against AD,
      exerts neuroprotection primarily through its antagonist activity on A2A adenosine
      receptors (A2AR), although it also inhibits A1Rs with similar potency. Still,
      studies on the specific involvement of these receptors in neuroprotection in a
      model of combined neurotoxicity (Abeta(25-35)+AlCl3) are missing. To address this
      issue, cultured SH-SY5Y cells exposed to Abeta(25-35)+AlCl3 were assessed for
      cell viability, morphology, intracellular ROS activity and expression of
      apoptosis-, stress- and AD-related proteins. To define the role of A1R and A2ARs,
      pretreatment with caffein, specific receptor antagonists (DPCPX or SCH58261) or
      siRNA-mediated gene knockdown were delivered. Results indicate that AlCl3
      treatment exacerbated Abeta(25-35) toxicity, increased ROS production, lipid
      peroxidation, beta-secretase-1 (BACE1) and amyloid precursor protein (APP).
      Interestingly, SCH58261 successfully prevented toxicity associated to Abeta(25
      35) only, whereas pretreatment with both DPCPX and SCH58261 was required to fully
      avert Abeta(25-35)+AlCl3-induced damage, suggesting that A1Rs might also be
      critically involved in protection during combined toxicity. The effects of
      caffein were mimicked by both N-acetyl cysteine, an antioxidant, and
      desferrioxamine, likely acting through distinct mechanisms. Altogether, our data
      establish a novel protective function associated with A1R inhibition in the
      setting of combined Abeta(25-35)+AlCl3 neurotoxicity, and expand our current
      knowledge on the potential beneficial role of caffein to prevent AD progression
      in subjects environmentally exposed to aluminum.

PMID- 25058313
TI  - Delineating the roles of neutrophils and macrophages in zebrafish regeneration
      models.
AB  - The outcome following injury can be healing, scarring or regeneration, all of
      which initiate within a resolving inflammatory response. Regeneration, comprising
      the complete anatomical and functional restoration of lost tissue with minimal
      residual consequence of injury, is the outcome that most holistically restores
      prior function. Leukocytes are recognized as playing an important role in
      determining the balance between fully regenerative or only partially reparative
      outcomes. Although macrophages have attracted considerable attention for their
      capacity to direct pro-regenerative outcomes, neutrophils are also key players in
      initiating inflammation and in influencing its ensuing outcome. In the context of
      prior studies investigating the role of neutrophils and macrophages in wound
      healing and in tissue/organ regeneration (mostly wound repair/healing models in
      mice), we comprehensively review the experimental possibilities that zebrafish
      models offer for delineating the individual and interactive contributions of
      neutrophils and macrophages to the regenerative process in embryos and adults.
      Zebrafish are a highly regenerative vertebrate and have a myeloid system very
      analogous to that of less-regenerative mammalian models. There are well
      characterized reporter lines for imaging and distinguishing neutrophil and
      macrophage behaviors in vivo, and tools enabling selective, independent
      manipulation of these two leukocyte lineages for functional studies. Zebrafish
      are an attractive model for delineating neutrophil and macrophage contributions
      not only to regeneration, but also to many other pathological processes. This
      article is part of a directed issue entitled: Regenerative Medicine: the
      challenge of translation. 

PMID- 25058315
TI  - Cell electrospinning cardiac patches for tissue engineering the heart.
AB  - Cell electrospinning has tremendous applicability to a wide range of uses within
      both the laboratory and clinic. This has directly resulted from the technology's
      unique ability to immobilize multiple cell types with a wide range of molecules
      simultaneously within a fiber during the scaffold generation process. The
      technology has been shown to generate many cell laden complex architectures from
      true three-dimensional sheets to those multi-core vessels. Although those studies
      have demonstrated the versatility of this platform biotechnology, we show here
      for the first time the ability to immobilize primary cardiac myocytes within
      these fibers in our quest to develop this technology for creating three
      dimensional cardiac patches which could be used for repairing, replacing and
      rejuvenating damaged, diseased and/or ageing cardiac tissues. These advances are
      unrivalled by any other technology currently available in the regenerative
      medicine toolbox, and have many interesting ramifications for repairing a damaged
      heart. 

PMID- 25058316
TI  - Successful detection, expression and purification of the alternatively spliced
      truncated Sm14 antigen of an Egyptian strain of Schistosoma mansoni.
AB  - Schistosoma mansoni causes intestinal schistosomiasis, a disease that is
      prevalent in several regions worldwide. To date, a protective vaccine against S.
      mansoni is still lacking. Several promising antigens have been discovered and
      evaluated for vaccine protection, such as Sm14 and Sm28GST. In this short
      communication, we report the successful detection of an alternatively spliced
      truncated form of Sm14 which was highly expressed in an Egyptian strain of S.
      mansoni. This truncated Sm14 (TrSm14) protein was formerly reported to be
      practically non-existent and its complementary DNA (cDNA) was thought to be 'a
      rare misprocessing of mRNA precursor'. Our finding demonstrates that there is
      inter-strain variation in the S. mansoni transcriptome and subsequently in the
      role/function of the expressed proteins. We expressed TrSm14 successfully in
      Escherichia coli as a fusion protein with the schistosomal antigen Sm28GST. The
      fusion protein was purified using metal affinity chromatography and was found to
      be reactive with serum from S. mansoni-infected patients. This suggests a
      possible diagnostic value for this protein in detection of anti-schistosomal
      antibodies. In addition, this fusion protein could offer a potential bivalent
      vaccine candidate against S. mansoni that is worthy of further investigation. 

PMID- 25058317
TI  - Kathu Townlands: a high density Earlier Stone Age locality in the interior of
      South Africa.
AB  - Kathu Townlands is a high density Earlier Stone Age locality in the Northern Cape
      Province, South Africa. Here we present the first detailed information on this
      locality based on analysis of a sample of lithic material from excavations by P.
      Beaumont and field observations made in the course of fieldwork in 2013. The
      results confirm the remarkably high artefact density at Kathu Townlands and do
      not provide evidence consistent with high energy transport as a mechanism of site
      formation, suggesting that Kathu Townlands was the site of intensive exploitation
      of highly siliceous outcroppings of banded iron formation. The results presented
      here provide a first step towards understanding this complex locality and point
      to the need for further research and the importance of preserving this locality
      in the face of intensive and rapid development. 

PMID- 25058318
TI  - Microbiota of healthy corals are active against fungi in a light-dependent
      manner.
AB  - Coral reefs are intricate ecosystems that harbor diverse organisms, including 25%
      of all marine fish. Healthy corals exhibit a complex symbiosis between coral
      polyps, endosymbiotic alga, and an array of microorganisms, called the coral
      holobiont. Secretion of specialized metabolites by coral microbiota is thought to
      contribute to the defense of this sessile organism against harmful biotic and
      abiotic factors. While few causative agents of coral diseases have been
      unequivocally identified, fungi have been implicated in the massive destruction
      of some soft corals worldwide. Because corals are nocturnal feeders, they may be
      more vulnerable to fungal infection at night, and we hypothesized that the coral
      microbiota would have the capability to enhance their defenses against fungi in
      the dark. A Pseudoalteromonas sp. isolated from a healthy octocoral displayed
      light-dependent antifungal properties when grown adjacent to Penicillium citrinum
      (P. citrinum) isolated from a diseased Gorgonian octocoral. Microbial MALDI
      imaging mass spectrometry (IMS) coupled with molecular network analyses revealed
      that Pseudoalteromonas produced higher levels of antifungal polyketide
      alteramides in the dark than in the light. The alteramides were inactivated by
      light through a photoinduced intramolecular cyclization. Further NMR studies led
      to a revision of the stereochemical structure of the alteramides. Alteramide A
      exhibited antifungal properties and elicited changes in fungal metabolite
      distributions of mycotoxin citrinin and citrinadins. These data support the
      hypothesis that coral microbiota use abiotic factors such as light to regulate
      the production of metabolites with specialized functions to combat opportunistic
      pathogens at night. 

PMID- 25058319
TI  - Uniform growth of high-quality oxide thin films on graphene using a CdSe quantum
      dot array seeding layer.
AB  - Graphene displays outstanding properties as an electrode and a semiconducting
      channel material for transistors; however, the weak interfacial bond between
      graphene and an inorganic oxide material-based insulator presents a major
      constraint on these applications. Here, we report a new approach to improving the
      interface between the two materials using a CdSe quantum dot (QD)-based seeding
      layer in an inorganic material-graphene junction. CdSe QDs were electrochemically
      grown on graphene without degrading the properties of the graphene layer. The
      graphene structure was then used as the electrode in an oxide semiconductor by
      depositing a zinc oxide thin film onto the graphene coated with a QD seed layer
      (QD/G). The zinc oxide film adhered strongly to the graphene layer and provided a
      low contact resistance. A high-k dielectric layer in the form of an HfO2 film,
      which is an essential element in the fabrication of high-performance graphene
      based field effect transistors, was also uniformly formed on the QD/G sheet using
      atomic layer deposition. The resulting transistors provided a relatively good
      performance, yielding hole and electron mobilities of 2600 and 2000 cm(2)/V.s. 

PMID- 25058320
TI  - A novel MVA vectored Chikungunya virus vaccine elicits protective immunity in
      mice.
AB  - BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with
      febrile illness often accompanied by rash and arthralgia that may persist for
      several years. Outbreaks are associated with high morbidity and create a public
      health challenge for countries affected. Recent outbreaks have occurred in both
      Europe and the Americas, suggesting CHIKV may continue to spread. Despite the
      sustained threat of the virus, there is no approved vaccine or antiviral therapy
      against CHIKV. Therefore, it is critical to develop a vaccine that is both well
      tolerated and highly protective. METHODOLOGY/PRINCIPAL FINDINGS: In this study,
      we describe the construction and characterization of a modified Vaccinia virus
      Ankara (MVA) virus expressing CHIKV E3 and E2 proteins (MVA-CHIK) that protected
      several mouse models from challenge with CHIKV. In particular, BALB/c mice were
      completely protected against viremia upon challenge with CHIKV after two doses of
      MVA-CHIK. Additionally, A129 mice (deficient in IFNalpha/beta) were protected
      from viremia, footpad swelling, and mortality. While high anti-virus antibodies
      were elicited, low or undetectable levels of neutralizing antibodies were
      produced in both mouse models. However, passive transfer of MVA-CHIK immune serum
      to naive mice did not protect against mortality, suggesting that antibodies may
      not be the main effectors of protection afforded by MVA-CHIK. Furthermore,
      depletion of CD4(+), but not CD8(+) T-cells from vaccinated mice resulted in 100%
      mortality, implicating the indispensable role of CD4(+) T-cells in the protection
      afforded by MVA-CHIK. CONCLUSIONS/SIGNIFICANCE: The results presented herein
      demonstrate the potential of MVA to effectively express CHIKV E3-E2 proteins and
      generate protective immune responses. Our findings challenge the assumption that
      only neutralizing antibodies are effective in providing protection against CHIKV,
      and provides a framework for the development of novel, more effective vaccine
      strategies to combat CHIKV.

PMID- 25058321
TI  - Medication incidents related to automated dose dispensing in community pharmacies
      and hospitals--a reporting system study.
AB  - INTRODUCTION: Automated dose dispensing (ADD) is being introduced in several
      countries and the use of this technology is expected to increase as a growing
      number of elderly people need to manage their medication at home. ADD aims to
      improve medication safety and treatment adherence, but it may introduce new
      safety issues. This descriptive study provides insight into the nature and
      consequences of medication incidents related to ADD, as reported by healthcare
      professionals in community pharmacies and hospitals. METHODS: The medication
      incidents that were submitted to the Dutch Central Medication incidents
      Registration (CMR) reporting system were selected and characterized independently
      by two researchers. MAIN OUTCOME MEASURES: Person discovering the incident, phase
      of the medication process in which the incident occurred, immediate cause of the
      incident, nature of incident from the healthcare provider's perspective, nature
      of incident from the patient's perspective, and consequent harm to the patient
      caused by the incident. RESULTS: From January 2012 to February 2013 the CMR
      received 15,113 incidents: 3,685 (24.4%) incidents from community pharmacies and
      11,428 (75.6%) incidents from hospitals. Eventually 1 of 50 reported incidents
      (268/15,113 = 1.8%) were related to ADD; in community pharmacies more incidents
      (227/3,685 = 6.2%) were related to ADD than in hospitals (41/11,428 = 0.4%). The
      immediate cause of an incident was often a change in the patient's medicine
      regimen or relocation. Most reported incidents occurred in two phases: entering
      the prescription into the pharmacy information system and filling the ADD bag.
      CONCLUSION: A proportion of incidents was related to ADD and is reported
      regularly, especially by community pharmacies. In two phases, entering the
      prescription into the pharmacy information system and filling the ADD bag, most
      incidents occurred. A change in the patient's medicine regimen or relocation was
      the immediate causes of an incident.

PMID- 25058322
TI  - Electrochemical device based on a Pt nanosphere-paper working electrode for in
      situ and real-time determination of the flux of H2O2 releasing from SK-BR-3
      cancer cells.
AB  - A novel paper working electrode with Pt nanospheres grown in it (Pt-PWE) was
      first used as a sensor platform and then cancer cells were immobilized on the Pt
      PWE (high affinity binding with aptamers). This electrode was first designed to
      achieve the in situ and real-time determination of H2O2 released from cancer
      cells to obtain an accurate determination. 

PMID- 25058323
TI  - Detecting in situ copepod diet diversity using molecular technique: development
      of a copepod/symbiotic ciliate-excluding eukaryote-inclusive PCR protocol.
AB  - Knowledge of in situ copepod diet diversity is crucial for accurately describing
      pelagic food web structure but is challenging to achieve due to lack of an easily
      applicable methodology. To enable analysis with whole copepod-derived DNAs, we
      developed a copepod-excluding 18S rDNA-based PCR protocol. Although it is
      effective in depressing amplification of copepod 18S rDNA, its applicability to
      detect diverse eukaryotes in both mono- and mixed-species has not been
      demonstrated. Besides, the protocol suffers from the problem that sequences from
      symbiotic ciliates are overrepresented in the retrieved 18S rDNA libraries. In
      this study, we designed a blocking primer to make a combined primer set
      (copepod/symbiotic ciliate-excluding eukaryote-common: CEEC) to depress PCR
      amplification of symbiotic ciliate sequences while maximizing the range of
      eukaryotes amplified. We firstly examined the specificity and efficacy of CEEC by
      PCR-amplifying DNAs from 16 copepod species, 37 representative organisms that are
      potential prey of copepods and a natural microplankton sample, and then evaluated
      the efficiency in reconstructing diet composition by detecting the food of both
      lab-reared and field-collected copepods. Our results showed that the CEEC primer
      set can successfully amplify 18S rDNA from a wide range of isolated species and
      mixed-species samples while depressing amplification of that from copepod and
      targeted symbiotic ciliate, indicating the universality of CEEC in specifically
      detecting prey of copepods. All the predetermined food offered to copepods in the
      laboratory were successfully retrieved, suggesting that the CEEC-based protocol
      can accurately reconstruct the diets of copepods without interference of copepods
      and their associated ciliates present in the DNA samples. Our initial application
      to analyzing the food composition of field-collected copepods uncovered diverse
      prey species, including those currently known, and those that are unsuspected, as
      copepod prey. While testing is required, this protocol provides a useful strategy
      for depicting in situ dietary composition of copepods. 

PMID- 25058325
TI  - Novel triphenylamine donors with carbazole moieties for organic sensitizers
      toward cobalt(II/III) redox mediators.
AB  - A series of D-pi-A organic dyes, X72-75, containing novel triarylamine electron
      donors have been synthesized for dye-sensitized solar cells (DSCs). The
      superiority of the asymmetric design of the triphenylamine electron donor over
      the symmetrical triphenylamine when applied in organic dyes for cobalt cells has
      been observed. Using X72 with the cobalt(II/III) redox shuttle resulted in an
      overall power conversion efficiency (PCE) of 9.18%, outperforming the state-of
      the-art dye C218 under the same conditions. 

PMID- 25058326
TI  - Cardiorespiratory fitness, physical activity, and quality of life in patients
      with McArdle disease.
AB  - BACKGROUND: This study sought to determine whether health-related quality of life
      (HRQoL) could be related to cardiorespiratory fitness (CRF) and/or physical
      activity (PA) in patients with McArdle disease and to compare the CRF and HRQoL
      data obtained with normative data for age- and sex-matched healthy subjects.
      METHODS: Eighty-one adult patients with McArdle disease underwent aerobic
      capacity testing to determine peak oxygen uptake (VO2peak), among other
      variables. HRQoL (Short Form 36-Item Health Survey questionnaire version 2 (SF-36
      version 2)) and PA (International Physical Activity Questionnaire) questionnaires
      were completed by 45 of the patients. HRQoL and VO2peak data were compared with
      published normative data. RESULTS: Positive correlations were observed between
      VO2peak and leisure time PA versus the physical component summary score and
      scores for several domains of the SF-36 questionnaire after adjusting for age,
      body mass index, and disease severity (R values, 0.42-0.68; all P < 0.01). In a
      regression analysis, the physical component summary score was directly linked to
      VO2peak (B = 1.28; 95% confidence interval, 0.78-1.78; P < 0.001; R = 0.422). The
      mean VO2peak recorded for patients with McArdle disease was 57% lower than the
      normative value (17.1 +/- 5.3 vs 40.0 +/- 9.5 mL.kg.min, respectively; P <
      0.001). All patients showed a CRF below their age-/sex-matched normality value
      and scored clinically lower in the physical component summary and in most SF-36
      domains compared with the Spanish general population. CONCLUSIONS: Patients
      showed a consistent link between higher physical HRQoL scores and higher CRF.
      Patients fulfilling leisure time PA recommendations showed higher CRF and
      physical HRQoL scores than those not meeting guideline recommendations. According
      to normative data for healthy subjects, CRF and physical HRQoL are severely
      impaired in adult patients with McArdle disease.

PMID- 25058324
TI  - Effects of increased CO2 on fish gill and plasma proteome.
AB  - Ocean acidification and warming are both primarily caused by increased levels of
      atmospheric CO2, and marine organisms are exposed to these two stressors
      simultaneously. Although the effects of temperature on fish have been
      investigated over the last century, the long-term effects of moderate CO2
      exposure and the combination of both stressors are almost entirely unknown. A
      proteomics approach was used to assess the adverse physiological and biochemical
      changes that may occur from the exposure to these two environmental stressors. We
      analysed gills and blood plasma of Atlantic halibut (Hippoglossus hippoglossus)
      exposed to temperatures of 12  degrees C (control) and 18  degrees C (impaired
      growth) in combination with control (400 uatm) or high-CO2 water (1000 uatm) for
      14 weeks. The proteomic analysis was performed using two-dimensional gel
      electrophoresis (2DE) followed by Nanoflow LC-MS/MS using a LTQ-Orbitrap. The
      high-CO2 treatment induced the up-regulation of immune system-related proteins,
      as indicated by the up-regulation of the plasma proteins complement component C3
      and fibrinogen beta chain precursor in both temperature treatments. Changes in
      gill proteome in the high-CO2 (18  degrees C) group were mostly related to
      increased energy metabolism proteins (ATP synthase, malate dehydrogenase, malate
      dehydrogenase thermostable, and fructose-1,6-bisphosphate aldolase), possibly
      coupled to a higher energy demand. Gills from fish exposed to high-CO2 at both
      temperature treatments showed changes in proteins associated with increased
      cellular turnover and apoptosis signalling (annexin 5, eukaryotic translation
      elongation factor 1gamma, receptor for protein kinase C, and putative ribosomal
      protein S27). This study indicates that moderate CO2-driven acidification, alone
      and combined with high temperature, can elicit biochemical changes that may
      affect fish health.

PMID- 25058327
TI  - No association between vitamin D deficiency and markers of bone health in
      athletes.
AB  - PURPOSE: Adequate vitamin D (25(OH)D) is required to maintain good bone health,
      yet many athletes are 25(OH)D deficient. This study sought to examine the
      relation between serum 25(OH)D and measures of bone health (bone mineral density
      (BMD) and T-score) in an ethnically diverse athletic population. METHODS: Nine
      hundred and fifty male athletes presented for precompetition medical assessment
      in our facility. An additional 436 individuals registered with a Qatari sporting
      federation (such as sailing, archery, shooting, bowling) but exercising <2 h.wk
      were used as control population. There were 30 Asian, 242 Black African, 235
      Caucasian, 491 from Gulf Cooperation Countries, 336 Middle Eastern, and 52
      Persian participants. All individuals undertook bone densitometry and body
      composition analysis by dual-energy x-ray absorptiometry and serum 25(OH)D
      evaluation. RESULTS: From 950 athletes, 17.5% demonstrated severe deficiency,
      39.2% demonstrated deficiency, 24.5% demonstrated insufficiency, and 18.8%
      demonstrated sufficiency, compared with 436 controls, 25.9% of whom demonstrated
      severe deficiency, 46.3% demonstrated deficiency, 19.0% demonstrated
      insufficiency, and 8.7% demonstrated sufficiency. No athlete presented with a T
      score suggestive of osteoporosis (-2.5 SD) or osteopenia (-1.0 SD) at hip total.
      After adjustment for age, anthropometry, ethnicity, and athletic participation,
      there was no association between 25(OH)D and any BMD and T-score at any site
      within athletes. African and Caucasian athletes present with greater (P < 0.05)
      BMD and T-scores at the spine, neck, and hip total than those of Asian, Gulf
      Cooperation Countries, Middle Eastern, and Persian ethnicities. Athletes
      participating in high-impact sports present with higher measures (P < 0.05) of
      bone health than control participants regardless of 25(OH)D status. CONCLUSIONS:
      There is no association between 25(OH)D and BMD and T-score for any site within
      male athletes after adjusting for age, ethnicity, and sporting participation.

PMID- 25058328
TI  - Associations among physical activity, diet quality, and weight status in US
      adults.
AB  - PURPOSE: Nearly 70% of adult Americans are overweight or obese, but the
      associations between physical activity, diet quality, and weight status have not
      been examined in a representative sample of US adults. The purpose of this study
      was to examine the associations among moderate-to-vigorous physical activity
      (MVPA), diet quality, and weight status within and across age groups in US
      adults. METHODS: Participants included 2587 men and 2412 women age 20 to >=70 yr
      from the National Health and Nutrition Examination Survey 2003-2004 and 2005
      2006. Physical activity was measured by accelerometry. Diet quality was assessed
      with overall Healthy Eating Index-2005 scores. Measures of weight status, body
      mass index (BMI), and waist circumference were assessed using standard National
      Health and Nutrition Examination Survey protocols. RESULTS: Across age groups,
      MVPA was lower in the older age groups for both men and women, whereas diet
      quality was higher (P < 0.001). BMI and waist circumference were also higher in
      the older age groups (P < 0.05). Within age groups, MVPA was inversely associated
      with BMI and waist circumference for men and women in nearly every age group (P <
      0.05). Diet quality was inversely associated with the weight status variables
      only in men age 30-39, 40-49 (BMI only), and 50-59 yr and women age 50-59 yr (P <
      0.05). CONCLUSIONS: We observed clear age-related trends for measures of weight
      status, physical activity, and diet quality in US men and women. MVPA was very
      consistently related to weight status in both genders. The relation between diet
      quality and weight status was less consistent. These findings provide support for
      public health efforts to prevent obesity by promoting increased physical activity
      in adult Americans.

PMID- 25058330
TI  - The auditory N1 amplitude for task-irrelevant probes reflects visual interest.
AB  - The present study examined the relationship between the amplitude of N1 component
      of event-related potentials (ERPs) elicited by task-irrelevant auditory probes
      and the observer's level of interest in co-occurring visual stimuli. Participants
      watched short animated video clips (about 400 s) played either forward
      (interesting) or backward (boring) accompanied by task-irrelevant sequence of
      auditory probes. The tone frequency of probes was fixed in a monotonous sequence
      condition but randomly varied in a variable sequence condition. The mean stimulus
      onset asynchrony of probes was 600 ms in both sequence conditions. Results showed
      that the N1 amplitude for probes in the variable sequence condition became
      smaller when participants watched interesting animated videos compared with their
      watching boring ones; a parallel effect was not observed in the monotonous
      sequence condition. Furthermore, analysis of sub-blocks (i.e., 360 s of the
      analysis time window for each animated video was divided into 20 s * 18 sub
      blocks) showed a significant correlation between the forward-minus-backward
      differences in scored interest levels with the N1 amplitude in the variable
      sequence condition. This finding points to the possibility that the observer's
      interest can be estimated by neurophysiological data just for 20 s. The present
      study should remarkably extend the usability of the task-irrelevant probe
      technique.

PMID- 25058329
TI  - Effects of reducing sedentary time on glucose metabolism in immigrant Pakistani
      men.
AB  - PURPOSE: This study aimed to examine the association between changes in
      objectively measured overall physical activity (PA) and changes in fasting and
      postprandial plasma insulin, C-peptide, and glucose concentrations in type 2
      diabetes-prone immigrant Pakistani men living in Norway and to examine whether
      this association is explained by changes in moderate and vigorous PA (MVPA) or
      changes in sedentary time. METHODS: The current study is a secondary cohort
      analysis on data collected from the Physical Activity and Minority Health study,
      a randomized controlled trial aimed at increasing the PA level, and not sedentary
      time per se, in a group of sedentary immigrant Pakistani men (n = 150). For the
      present analyses, the two groups were merged and a cohort analysis was performed.
      Overall PA (counts per minute) and its subcomponents, sedentary time and MVPA,
      were measured with accelerometry. Outcome variables were measured after a 2-h
      standardized glucose tolerance test. RESULTS: Change in overall PA was
      significantly associated with postprandial log-transformed plasma insulin (beta =
      -0.002; 95% confidence interval (CI), -0.003 to 0.000; P = 0.008), C-peptide
      (beta = -2.7; 95% CI, -4.9 to -0.5; P = 0.01), and glucose concentration (beta = 
      0.006; 95% CI, -0.01 to -0.002; P = 0.002). Change in sedentary time was
      significantly and beneficially associated with changes in postprandial log
      transformed plasma insulin (beta = 0.002; 95% CI, 0.001-0.003; P = 0.001), C
      peptide (beta = 3.7; 95% CI, 1.5-6.0; P = 0.001), and glucose concentration (beta
      = 0.006; 95% CI, 0.002-0.1; P = 0.002), independent of changes in MVPA, waist
      circumference, and other confounders. CONCLUSIONS: Increasing overall PA by
      reducing sedentary time seems as important as increasing time spent at MVPA in
      relation to postprandial plasma insulin and glucose levels in diabetes-prone
      immigrant men.

PMID- 25058331
TI  - Breast milk metabolome characterization in a single-phase extraction,
      multiplatform analytical approach.
AB  - Breast milk (BM) is a biofluid that has a fundamental role in early life
      nutrition and has direct impact on growth, neurodevelopment, and health. Global
      metabolic profiling is increasingly being utilized to characterize complex
      metabolic changes in biological samples. However, in order to achieve broad
      metabolite coverage, it is necessary to employ more than one analytical platform,
      typically requiring multiple sample preparation protocols. In an effort to
      improve analytical efficiency and retain comprehensive coverage of the
      metabolome, a new extraction methodology was developed that successfully retains
      metabolites from BM in a single-phase using an optimized methyl-tert-butyl ether
      solvent system. We conducted this single-phase extraction procedure on a
      representative pool of BM, and characterized the metabolic composition using LC
      QTOF-MS and GC-Q-MS for polar and lipidic metabolites. To ensure that the
      extraction method was reproducible and fit-for-purpose, the analytical procedure
      was evaluated on both platforms using 18 metabolites selected to cover a range of
      chromatographic retention times and biochemical classes. Having validated the
      method, the metabolic signature of BM composition was mapped as a metabolic
      reaction network highlighting interconnected biological pathways and showing that
      the LC-MS and GC-MS platforms targeted largely different domains of the network.
      Subsequently, the same protocol was applied to ascertain compositional
      differences between BM at week 1 (n = 10) and 4 weeks (n = 9) post-partum. This
      single-phase approach is more efficient in terms of time, simplicity, cost, and
      sample volume than the existing two-phase methods and will be suited to high
      throughput metabolic profiling studies of BM. 

PMID- 25058332
TI  - Crystal structure of serine acetyl transferase from Brucella abortus and its
      complex with coenzyme A.
AB  - Brucella abortus is the major cause of premature foetal abortion in cattle, can
      be transmitted from cattle to humans, and is considered a powerful biological
      weapon. De novo cysteine biosynthesis is one of the essential pathways reported
      in bacteria, protozoa, and plants. Serine acetyltransferase (SAT) initiates this
      reaction by catalyzing the formation of O-acetylserine (OAS) using l-serine and
      acetyl coenzyme A as substrates. Here we report kinetic and crystallographic
      studies of this enzyme from B. abortus. The kinetic studies indicate that
      cysteine competitively inhibits the binding of serine to B. abortus SAT (BaSAT)
      and noncompetitively inhibits the binding of acetyl coenzyme A. The crystal
      structures of BaSAT in its apo state and in complex with coenzyme A (CoA) were
      determined to 1.96A and 1.87A resolution, respectively. BaSAT was observed as a
      trimer in a size exclusion column; however, it was seen as a hexamer in dynamic
      light scattering (DLS) studies and in the crystal structure, indicating it may
      exist in both states. The complex structure shows coenzyme A bound to the C
      terminal region, making mostly hydrophobic contacts from the center of the active
      site extending up to the surface of the protein. There is no conformational
      difference in the enzyme between the apo and the complexed states, indicating
      lock and key binding and the absence of an induced fit mechanism. 

PMID- 25058333
TI  - How do women prepare for pregnancy? Preconception experiences of women attending
      antenatal services and views of health professionals.
AB  - MAIN OBJECTIVE: To determine the extent to which women plan and prepare for
      pregnancy. METHODS: Cross-sectional questionnaire survey of pregnant women
      attending three maternity services in London about knowledge and uptake of
      preconception care; including a robust measure of pregnancy planning, and phone
      interviews with a range of health care professionals. MAIN RESULTS: We recruited
      1173/1288 (90%) women, median age of 32 years. 73% had clearly planned their
      pregnancy, 24% were ambivalent and only 3% of pregnancies were unplanned. 51% of
      all women and 63% of those with a planned pregnancy took folic acid before
      pregnancy. 21% of all women reported smoking and 61% reported drinking alcohol in
      the 3 months before pregnancy; 48% of smokers and 41% of drinkers reduced or
      stopped before pregnancy. The 51% of all women who reported advice from a health
      professional before becoming pregnant were more likely to adopt healthier
      behaviours before pregnancy [adjusted odds ratios for greatest health
      professional input compared with none were 2.34 (95% confidence interval 1.54
      3.54) for taking folic acid and 2.18 (95% CI 1.42-3.36) for adopting a healthier
      diet before pregnancy]. Interviews with 20 health professionals indicated low
      awareness of preconception health issues, missed opportunities and confusion
      about responsibility for delivery of preconception care. SIGNIFICANCE OF THE
      FINDINGS: Despite a high level of pregnancy planning, awareness of preconception
      health among women and health professionals is low, and responsibility for
      providing preconception care is unclear. However, many women are motivated to
      adopt healthier behaviours in the preconception period, as indicated by halving
      of reported smoking rates in this study. The link between health professional
      input and healthy behaviour change before pregnancy is a new finding that should
      invigorate strategies to improve awareness and uptake of pre-pregnancy health
      care, and bring wider benefits for public health.

PMID- 25058335
TI  - Optic nerve pit-associated choroidal cleft.

PMID- 25058334
TI  - UVB induces a genome-wide acting negative regulatory mechanism that operates at
      the level of transcription initiation in human cells.
AB  - Faithful transcription of DNA is constantly threatened by different endogenous
      and environmental genotoxic effects. Transcription coupled repair (TCR) has been
      described to stop transcription and quickly remove DNA lesions from the
      transcribed strand of active genes, permitting rapid resumption of blocked
      transcription. This repair mechanism has been well characterized in the past
      using individual target genes. Moreover, numerous efforts investigated the fate
      of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested
      that stopped Pol II complexes can either backtrack, be removed and degraded or
      bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose
      of UVB on global DNA-bound Pol II distribution in human cells. We found that the
      used UVB dose did not induce Pol II degradation however surprisingly at about 93%
      of the promoters of all expressed genes Pol II occupancy was seriously reduced 2
      4 hours following UVB irradiation. The presence of Pol II at these cleared
      promoters was restored 5-6 hours after irradiation, indicating that the negative
      regulation is very dynamic. We also identified a small set of genes (including
      several p53 regulated genes), where the UVB-induced Pol II clearing did not
      operate. Interestingly, at promoters, where Pol II promoter clearance occurs,
      TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these
      genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR
      machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B
      protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters.
      Thus, our study reveals a UVB induced negative regulatory mechanism that targets
      Pol II transcription initiation on the large majority of transcribed gene
      promoters, and a small subset of genes, where Pol II escapes this negative
      regulation. 

PMID- 25058336
TI  - From PET/CT to PET/MRI: advances in instrumentation and clinical applications.
AB  - Multimodality imaging of positron emission tomography/computed tomography
      (PET/CT) provides both metabolic information and the anatomic structure, which is
      significantly superior to either PET or CT alone and has greatly improved its
      clinical applications. Because of the higher soft-tissue contrast of magnetic
      resonance imaging (MRI) and no extra ionizing radiation, PET/MRI imaging is the
      hottest topic currently. PET/MRI is swiftly making its way into clinical
      practice. However, it has many technical difficulties to overcome, such as
      photomultiplier tubes, which cannot work properly in a magnetic field, and the
      inability to provide density information on the object for attenuation
      correction. This paper introduces the technique process of PET/MRI and summarizes
      its clinical applications, including imaging in oncology, neurology, and
      cardiology. 

PMID- 25058337
TI  - A new prognostic score for elderly patients with diffuse large B-cell lymphoma
      treated with R-CHOP: the prognostic role of blood monocyte and lymphocyte counts
      is absent.
AB  - BACKGROUND: Absolute lymphocyte count (ALC) and absolute monocyte count (AMC)
      have been documented as independent predictors of survival in patients with newly
      diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic
      impact of ALC and AMC in the context of International Prognostic Index (IPI) and
      other significant variables in elderly population treated in the R-CHOP regime
      has not been carried out yet. METHODOLOGY/PRINCIPAL FINDINGS: In this
      retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age >=
      60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive
      statistical analysis was performed to identify risk factors of 3-year overall
      survival (OS). In multivariate analysis, only three predictors proved
      significant: Eastern Cooperative Oncology Group performance status (ECOG), age
      and bulky disease presence. These predictors were dichotomized (ECOG >= 1, age >=
      70, bulk >= 7.5) to create a novel four-level score. This score predicted 3-year
      OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high
      intermediate and high-risk groups, respectively (P<0.001). Further, a three-level
      score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%,
      36.2% in the low, intermediate and high-risk groups, respectively) but is more
      difficult to interpret. Both the 3- and 4-level scores were compared to standard
      scoring systems and, in our population, were shown to be superior in terms of
      patients risk stratification with respect to 3-year OS prediction. The results
      were successfully validated on an independent cohort of 162 patients of similar
      group characteristics. CONCLUSIONS: The prognostic role of baseline ALC, AMC or
      their ratio (LMR) was not confirmed in the multivariate context in elderly
      population with DLBCL treated with R-CHOP. The newly proposed age-specific index
      stratifies the elderly population into risk groups more precisely than the
      conventional IPI and its existing variants.

PMID- 25058339
TI  - Upper limits to the reaction rate coefficients of C(n)(-) and C(n)H(-) (n = 2, 4,
      6) with molecular hydrogen.
AB  - In the interstellar medium (ISM) ion-molecule reactions play a key role in
      forming complex molecules. Since 2006, after the radioastronomical discovery of
      the first of by now six interstellar anions, interest has grown in understanding
      the formation and destruction pathways of negative ions in the ISM. Experiments
      have focused on reactions and photodetachment of the identified negatively
      charged ions. Hints were found that the reactions of CnH(-) with H2 may proceed
      with a low (<10(-13) cm(3) s(-1)), but finite rate [Eichelberger, B.; et al.
      Astrophys. J. 2007, 667, 1283]. Because of the high abundance of molecular
      hydrogen in the ISM, a precise knowledge of the reaction rate is needed for a
      better understanding of the low-temperature chemistry in the ISM. A suitable tool
      to analyze rare reactions is the 22-pole radiofrequency ion trap. Here, we report
      on reaction rates for Cn(-) and CnH(-) (n = 2, 4, 6) with buffer gas temperatures
      of H2 at 12 and 300 K. Our experiments show the absence of these reactions with
      an upper limit to the rate coefficients between 4 * 10(-16) and 5 * 10(-15) cm(3)
      s(-1), except for the case of C2(-), which does react with a finite rate with H2
      at low temperatures. For the cases of C2H(-) and C4H(-), the experimental results
      were confirmed with quantum chemical calculations. In addition, the possible
      influence of a residual reactivity on the abundance of C4H(-) and C6H(-) in the
      ISM were estimated on the basis of a gas-phase chemical model based on the KIDA
      database. We found that the simulated ion abundances are already unaffected if
      reaction rate coefficients with H2 were below 10(-14) cm(3) s(-1).

PMID- 25058338
TI  - Web-based computational chemistry education with CHARMMing II: Coarse-grained
      protein folding.
AB  - A lesson utilizing a coarse-grained (CG) Go-like model has been implemented into
      the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org) to
      the Chemistry at HARvard Macromolecular Mechanics (CHARMM) molecular simulation
      package. While widely used to model various biophysical processes, such as
      protein folding and aggregation, CG models can also serve as an educational tool
      because they can provide qualitative descriptions of complex biophysical
      phenomena for a relatively cheap computational cost. As a proof of concept, this
      lesson demonstrates the construction of a CG model of a small globular protein,
      its simulation via Langevin dynamics, and the analysis of the resulting data.
      This lesson makes connections between modern molecular simulation techniques and
      topics commonly presented in an advanced undergraduate lecture on physical
      chemistry. It culminates in a straightforward analysis of a short dynamics
      trajectory of a small fast folding globular protein; we briefly describe the
      thermodynamic properties that can be calculated from this analysis. The
      assumptions inherent in the model and the data analysis are laid out in a clear,
      concise manner, and the techniques used are consistent with those employed by
      specialists in the field of CG modeling. One of the major tasks in building the
      Go-like model is determining the relative strength of the nonbonded interactions
      between coarse-grained sites. New functionality has been added to CHARMMing to
      facilitate this process. The implementation of these features into CHARMMing
      helps automate many of the tedious aspects of constructing a CG Go model. The CG
      model builder and its accompanying lesson should be a valuable tool to chemistry
      students, teachers, and modelers in the field.

PMID- 25058340
TI  - Taurine chloramine-induced inactivation of cofilin protein through methionine
      oxidation.
AB  - Cofilin regulates reorganization of actin filaments (F-actin) in eukaryotes. A
      recent finding has demonstrated that oxidation of cofilin by taurine chloramine
      (TnCl), a physiological oxidant derived from neutrophils, causes cofilin to
      translocate to the mitochondria inducing apoptosis (F. Klamt et al. Nat. Cell
      Biol.11:1241-1246; 2009). Here we investigated the effect of TnCl on biological
      activities of cofilin in vitro. Our data show that TnCl-induced oxidation of
      recombinant human cofilin-1 inhibits its F-actin-binding and depolymerization
      activities. Native cofilin contains four free Cys and three Met residues.
      Incubation of oxidized cofilin with DTT does not lead to its reactivation. A
      double Cys to Ala mutation on the two C-terminal Cys shows similar biological
      activities as the wild type, but does not prevent the TnCl-induced inactivation.
      In contrast, incubation of oxidized cofilin with methionine sulfoxide reductases
      results in its reactivation. Phosphorylation is known to inhibit cofilin
      activities. We found that Met oxidation also prevents phosphorylation of cofilin,
      which is reversed by incubating oxidized cofilin with methionine sulfoxide
      reductases. Interestingly, intact protein mass spectrometry of the oxidized
      mutant indicated one major oxidation product with an additional mass of 16 Da,
      consistent with oxidation of one specific Met residue. This residue was
      identified as Met-115 by peptide mapping and tandem mass spectrometry. It is
      adjacent to Lys-114, a known residue on globular-actin-binding site, implying
      that oxidation of Met-115 disrupts the globular-actin-binding site of cofilin,
      which causes TnCl-induced inactivation. The findings identify Met-115 as a redox
      switch on cofilin that regulates its biological activity. 

PMID- 25058341
TI  - Vertically pi-expanded coumarin--synthesis via the Scholl reaction and
      photophysical properties.
AB  - A short and efficient access to a unique type of pi-expanded coumarin is
      achieved. The strategic placement of naphthalene at the 4-position of coumarin
      allowed us to fuse these two moieties via aromatic dehydrogenation under Scholl
      conditions. The intriguing optical properties of this pi-expanded coumarin are
      discussed on the basis of quantum chemical calculations. The fluorescence quantum
      yield (~20%) is significantly higher than that obtained for the classical 7
      hydroxycoumarin. The ratio of emission versus radiationless deactivation is
      governed by the following factors: decrease in the oscillator strength of the SS
      transition (vs. perylene), low yield of intersystem crossing and strong internal
      conversion originating from the activity of the number of vibronic states. 

PMID- 25058343
TI  - Divergence of trends in US and UK aggregate exergy efficiencies 1960-2010.
AB  - National exergy efficiency analysis relates the quality of primary energy inputs
      to an economy with end useful work in sectoral energy uses such as transport,
      heat and electrical devices. This approach has been used by a range of authors to
      explore insights to macroscale energy systems and linkages with economic growth.
      However, these analyses use a variety of calculation methods with sometimes
      coarse assumptions, inhibiting comparisons. Therefore, building on previous
      studies, this paper first contributes toward a common useful work accounting
      framework, by developing more refined methodological techniques for electricity
      end use and transport exergy efficiencies. Second, to test this more consistent
      and granular approach, these advances are applied to the US and UK for 1960 to
      2010. The results reveal divergent aggregate exergy efficiencies: US efficiency
      remains stable at around 11%, while UK efficiency rises from 9% to 15%. The US
      efficiency stagnation is due to "efficiency dilution", where structural shifts to
      lower efficiency consumption (e.g., air-conditioning) outweigh device-level
      efficiency gains. The results demonstrate this is an important area of research,
      with consequent implications for national energy efficiency policies. 

PMID- 25058342
TI  - The frustrated host response to Legionella pneumophila is bypassed by MyD88
      dependent translation of pro-inflammatory cytokines.
AB  - Many pathogens, particularly those that require their host for survival, have
      devised mechanisms to subvert the host immune response in order to survive and
      replicate intracellularly. Legionella pneumophila, the causative agent of
      Legionnaires' disease, promotes intracellular growth by translocating proteins
      into its host cytosol through its type IV protein secretion machinery. At least 5
      of the bacterial translocated effectors interfere with the function of host cell
      elongation factors, blocking translation and causing the induction of a unique
      host cell transcriptional profile. In addition, L. pneumophila also interferes
      with translation initiation, by preventing cap-dependent translation in host
      cells. We demonstrate here that protein translation inhibition by L. pneumophila
      leads to a frustrated host MAP kinase response, where genes involved in the
      pathway are transcribed but fail to be translated due to the bacterium-induced
      protein synthesis inhibition. Surprisingly, few pro-inflammatory cytokines, such
      as IL-1alpha and IL-1beta, bypass this inhibition and get synthesized in the
      presence of Legionella effectors. We show that the selective synthesis of these
      genes requires MyD88 signaling and takes place in both infected cells that harbor
      bacteria and neighboring bystander cells. Our findings offer a perspective of how
      host cells are able to cope with pathogen-encoded activities that disrupt normal
      cellular process and initiate a successful inflammatory response. 

PMID- 25058344
TI  - Metal complexes with 2-acetylpyridine-N(4)-orthochlorophenylthiosemicarbazone:
      cytotoxicity and effect on the enzymatic activity of thioredoxin reductase and
      glutathione reductase.
AB  - Metal complexes with 2-acetylpyridine-N(4)-orthochlorophenylthiosemicarbazone
      (H2Ac4oClPh) were assayed for their cytotoxicity against MCF-7 breast
      adenocarcinoma and HT-29 colon carcinoma cells. The thiosemicarbazone and most of
      the complexes were highly cytotoxic. H2Ac4oClPh and its gallium(III) and tin(IV)
      complexes did not show any inhibitory activity against thioredoxin reductase
      (TrxR) and glutathione reductase (GR). The palladium(II), platinum(II) and
      bismuth(III) complexes inhibited TrxR at micromolar concentrations but not GR.
      The antimony(III) and gold(III) complexes strongly inhibited TrxR at
      submicromolar doses with GR inhibition at higher concentrations. The selectivity
      of these complexes for TrxR suggests metal binding to a selenol residue in the
      active site of the enzyme. TrxR inhibition is likely a contributing factor to the
      mode of action of the gold and antimony derivatives. 

PMID- 25058345
TI  - Metabolome analysis of Arabidopsis thaliana roots identifies a key metabolic
      pathway for iron acquisition.
AB  - Fe deficiency compromises both human health and plant productivity. Thus, it is
      important to understand plant Fe acquisition strategies for the development of
      crop plants which are more Fe-efficient under Fe-limited conditions, such as
      alkaline soils, and have higher Fe density in their edible tissues. Root
      secretion of phenolic compounds has long been hypothesized to be a component of
      the reduction strategy of Fe acquisition in non-graminaceous plants. We therefore
      subjected roots of Arabidopsis thaliana plants grown under Fe-replete and Fe
      deplete conditions to comprehensive metabolome analysis by gas chromatography
      mass spectrometry and ultra-pressure liquid chromatography electrospray
      ionization quadrupole time-of-flight mass spectrometry. Scopoletin and other
      coumarins were found among the metabolites showing the strongest response to two
      different Fe-limited conditions, the cultivation in Fe-free medium and in medium
      with an alkaline pH. A coumarin biosynthesis mutant defective in ortho
      hydroxylation of cinnamic acids was unable to grow on alkaline soil in the
      absence of Fe fertilization. Co-cultivation with wild-type plants partially
      rescued the Fe deficiency phenotype indicating a contribution of extracellular
      coumarins to Fe solubilization. Indeed, coumarins were detected in root exudates
      of wild-type plants. Direct infusion mass spectrometry as well as UV/vis
      spectroscopy indicated that coumarins are acting both as reductants of Fe(III)
      and as ligands of Fe(II). 

PMID- 25058346
TI  - Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative
      breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study).
AB  - INTRODUCTION: Previous small-molecule antiangiogenics have compromised
      chemotherapy dose intensity in breast cancer. We present a phase I trial of a
      novel selective agent, nintedanib, plus standard chemotherapy in early breast
      cancer. METHODS: Her-2-negative breast cancer patients with tumours larger than 2
      cm were eligible for dose-escalation trial (classic 3+3 method). RESULTS: The
      recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with
      standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide.
      The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose
      intensity was ~100%. The pathologic complete response was 50%. CONCLUSIONS: The
      combination allows the delivery of full-dose intensity, while efficacy seems
      promising.

PMID- 25058347
TI  - Lack of BAP1 protein expression in uveal melanoma is associated with increased
      metastatic risk and has utility in routine prognostic testing.
AB  - BACKGROUND: The absence of BRCA1-associated protein 1 (BAP1) expression in uveal
      melanoma (UM) is associated with metastatic progression and reduced survival. In
      this study, we examine nuclear BAP1 (nBAP1) protein expression in primary UMs
      (PUMs) that show both 'typical' and 'atypical' clinical courses according to
      their chromosome 3 status, and secondary hepatic metastatic UM (MUM), correlating
      the results with histological, clinical and survival data. METHODS: Nuclear BAP1
      expression was immunohistochemically assessed in tissue microarrays (TMAs) of:
      (a) 68 PUM patients, who had been treated surgically; and (b) 13 MUM patients,
      with 5 cases being paired with primary tumour tissue. All cases were fully
      annotated. The percentage of tumour cell nuclei staining positively for BAP1 was
      scored by independent observers. RESULTS: Nuclear BAP1 protein expression was
      absent in 35 out of 68 (51%) PUM patients, correlating strongly with poor
      prognostic clinicopathological and genetic parameters and reduced survival (Log
      rank, P<0.001). Lack of nBAP1 expression importantly identified a subset of
      'atypical' PUM patients with disomy of chromosome 3 but with unexpected
      metastatic relapse. Nuclear BAP1 expression was absent in 10 out of 13 (77%) MUM
      and expression was concordant in all paired PUM and MUM patients. CONCLUSIONS:
      Absent nBAP1 protein expression is an independent survival predictor for UM
      patients, easily examined using immunohistochemistry.

PMID- 25058348
TI  - Associations between human papillomavirus and history of cancer among U.S. adults
      in the National Health and Nutrition Examination Survey (2003-2010).
AB  - BACKGROUND: Human papillomavirus (HPV) is an infectious agent that has been
      associated with human cancer. We have updated the U.S. population sero-prevalence
      using a large National Health and Nutrition Examination Survey (NHANES) sample of
      adults from 2003 to 2010, and have analysed the associations between HPV
      seropositivity and self-reported history of cancer. METHODS: Four cross-sectional
      cycles (2003-2004, 2005-2006, 2007-2008, and 2009-2010) were used, for a total of
      12 759 participants who had both cancer history and HPV serum information.
      RESULTS: The sero-prevalences of HPV types 6, 11, 16, and 18 were 15.0%, 4.8%,
      11.5%, and 4.1%, respectively. Females had significantly higher HPV prevalence
      than males (P<0.05) for all subtypes. Positive associations between HPV 16/18
      seropositivity and lifetime history of any cancer (adjusted odds ratio
      ORadj=1.68; 95% CI: 1.35, 2.01), history of any of eight selected cancers
      (ORadj=2.63; 95% CI: 1.78, 3.90), lung cancer (ORadj=5.14; 95% CI: 1.29, 20.44),
      and cervical cancer (ORadj=2.55; 95% CI: 1.63, 3.98) were observed. CONCLUSIONS:
      The finding of significant associations between HPV 16/18 seropositivity and
      lifetime history of cancer adds epidemiological evidence to the carcinogenicity
      potential of HPV 16 and 18 in other tissues. With increasing coverage of the HPV
      vaccine in the U.S., future NHANES data and sample collection may allow further
      detailed evaluation of the population impact of the HPV vaccination on cancer
      prevention.

PMID- 25058349
TI  - Tumour microenvironment of both early- and late-stage colorectal cancer is
      equally immunosuppressive.
AB  - BACKGROUND: Tumour microenvironment (TME) of advanced colorectal cancer (CRC)
      suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the
      microenvironment of early-stage tumours influences DCs. METHODS: Tumour
      conditioned media (TCM) was generated by culturing explant tumour tissue in vitro
      (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were
      pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation
      was assessed by flow cytometry and cytokine production measured by ELISA.
      RESULTS: TCM from both early- and late-staged tumours abrogated LPS-induction of
      IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators
      in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC
      patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate
      expression of maturation markers in response to LPS. Furthermore, in vitro
      culture of autologous DCs with TCM did not change the hypo-responsiveness of
      patient DCs. CONCLUSION: Our data demonstrates that the TME of all stages of CRC
      contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained
      from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse
      the negative influence of the TME on DCs will optimise cancer vaccines in both
      early- and late-stage CRC.

PMID- 25058350
TI  - Intraarterial chemotherapy as the first-line therapy in penile cancer.
AB  - BACKGROUND: Limited literature on the role of intraarterial chemotherapy as first
      line therapy for penile squamous cell carcinoma is available. METHODS: From 2005
      to 2013, a total of 12 patients with various stages of penile squamous cell
      carcinoma received intraarterial chemotherapy. The chemotherapeutic agents used
      were methotrexate, mitomycin C, bleomycin, cisplatin, and 5-fluorouracil. Surgery
      was followed by the tumour responses. RESULTS: An objective tumour response was
      noted in 10 of 12 patients (83%, 4 complete responders and 6 partial responders).
      In node-negative patients (n=7), the response rate was 100% (4 complete
      responders and 3 partial responders). Even in advanced penile squamous cell
      carcinoma with nodal invasion, a response rate of 60% could be achieved. Grade 2
      anorexia was the most frequent chemotherapy-related toxicity and no toxic death
      was noted. Recurrence-free survival was significantly better in patients without
      lymph node invasion (log-rank test, P=0.041). CONCLUSIONS: Neoadjuvant
      intraarterial chemotherapy displayed excellent responses for penile squamous cell
      carcinoma. This therapy could effectively shrink the tumour burden or even
      achieve complete response before surgery. It could be used as first-line strategy
      for penile cancer treatment because of low toxicity.

PMID- 25058352
TI  - Thermoelectric transport in Cu7PSe6 with high copper ionic mobility.
AB  - Building on the good thermoelectric performances of binary superionic compounds
      like Cu2Se, Ag2Se and Cu2S, a better and more detailed understanding of phonon
      liquid electron-crystal (PLEC) thermoelectric materials is desirable. In this
      work we present the thermoelectric transport properties of the compound Cu7PSe6
      as the first representative of the class of argyrodite-type ion conducting
      thermoelectrics. With a huge variety of possible compositions and high ionic
      conductivity even at room temperature, the argyrodites represent a very good
      model system to study structure-property relationships for PLEC thermoelectric
      materials. We particularly highlight the extraordinary low thermal conductivity
      of Cu7PSe6 below the glass limit, which can be associated with the molten copper
      sublattice leading to a softening of phonon modes. 

PMID- 25058351
TI  - Comment on 'TAp63 suppress metastasis via miR-133b in colon cancer cells'.

PMID- 25058353
TI  - Efficacy of memory rehabilitation therapy: a meta-analysis of TBI and stroke
      cognitive rehabilitation literature.
AB  - OBJECTIVE: To examine the efficacy of cognitive rehabilitation strategies
      specifically designed to improve memory after traumatic brain injury (TBI) and
      stroke vs. memory improvement with the passage of time. DESIGN AND METHODS: A
      meta-analysis was performed on 26 studies of memory retraining and recovery that
      were published between the years of 1985 and 2013. Effect sizes (ESs) from each
      study were calculated and converted to Pearson's r and then analysed to assess
      the overall effect size and the relationship among the ESs, patient demographics
      and treatment interventions. RESULTS: RESULTS indicated a significant average ES
      (r = 0.51) in the treatment intervention conditions, as well as a significant
      average ES (r = 0.31) in the control conditions, in which participants did not
      receive any treatment. The largest ESs occurred in studies of stroke patients and
      studies concerning working memory rehabilitation. CONCLUSIONS: RESULTS showed
      that memory rehabilitation was an effective therapeutic intervention, especially
      for stroke patients and for working memory as a treatment domain. However, the
      results also indicated that significant memory improvement occurred spontaneously
      over time.

PMID- 25058354
TI  - Autocrine positive regulatory feedback of glucocorticoid secretion:
      glucocorticoid receptor directly impacts H295R human adrenocortical cell
      function.
AB  - Glucocorticoid receptor (GR), a ubiquitous transcriptional factor, regulates
      target gene expression upon activation by glucocorticoids, notably cortisol, a
      corticosteroid hormone synthesized in the adrenal cortex. We thus hypothesized
      that both GR and cortisol might be involved in the regulation of adrenal
      physiology and steroidogenesis in an autocrine manner. In a cortisol-secreting
      human adrenocortical cell line (H295R), the GR-dependent signaling pathway was
      pharmacologically modulated either by dexamethasone (DEX), a GR agonist or by
      RU486, a GR antagonist, or was knocked-down by small interfering RNA strategy
      (SiRNA). We showed that GR activation, elicited by 48 h exposure to DEX, exerts a
      global positive regulatory effect on adrenal steroidogenesis as revealed by a 1.5
      to 2-fold increase in cortisol, 11-deoxycortisol and 17-hydroxyprogesterone
      secretion associated with a significant enhanced expression of steroidogenesis
      factors such as StAR, CYP11A1, CYP21A2 and CYP11B1. In sharp contrast, RU486
      treatment exerted opposite effects by decreasing both steroid production and
      expression of these steroidogenic factors. Likewise, GR repression by SiRNA also
      significantly reduced StAR, CYP11A1, and CYP11B1 mRNA levels. Interestingly,
      RU486 resulted in a significant CYP21A2 enzymatic blockade as demonstrated by a
      massive increase in 17-hydroxyprogesterone concentrations in RU486-treated H295R
      cell supernatants, while cortisol and 11-deoxycortisol secretions were reduced by
      more than 60%. Consistently, we also demonstrated that metabolic conversion of 17
      hydroxyprogesterone into 11-deoxycortisol onto H295R cells was drastically
      blunted in the presence of RU 486. Finally, steady state levels of MC2R
      transcripts encoding for the ACTH receptor were significantly induced by DEX,
      unlikely through a direct GR-mediated transcriptional activation as opposed to
      CYP11A1 and FKBP5 target genes. These results could account for a higher
      glucocorticoid-elicited ACTH sensitivity of adrenocortical cells. Our study
      identifies a positive ultra-short regulatory loop exerted by GR on
      steroidogenesis in H295R cells, thus supporting a complex intra-adrenal GR
      mediated feedback, likely relevant for human adrenocortical pathologies. 

PMID- 25058363
TI  - Lung transplantation for interstitial lung diseases.
AB  - PURPOSE OF REVIEW: An overview over the role of lung transplantation in
      interstitial lung diseases will be given. RECENT FINDINGS: Lung transplantation
      is an established therapy option for patients with various end-stage lung
      diseases. Currently, the worldwide procedural frequency is about 3600 per year.
      Unfortunately, the shortage of donor organs leads to approximately every sixth
      patient in western countries dying before a donor organ is available. The most
      frequent underlying clinical indications are emphysema, pulmonary fibrosis, and
      cystic fibrosis. In a recent registry report worldwide, 23% of all lung
      transplant recipients had a diagnosis of idiopathic pulmonary fibrosis. In
      experienced centers, candidates for transplantation are chosen according to
      disease-specific factors after excluding contra-indications. However, there are
      several challenges for lung transplantation. The number of lung transplantations
      performed is limited by the supply of donor organs, and the long-term survival
      rates are still inferior compared with other forms of solid organ
      transplantation. SUMMARY: Lung transplantation offers a survival benefit in
      carefully selected patients with interstitial lung diseases.

PMID- 25058364
TI  - Evolution of the AKH/corazonin/ACP/GnRH receptor superfamily and their ligands in
      the Protostomia.
AB  - In this review we trace the evolutionary connections between GnRH receptors from
      vertebrates and the receptors for adipokinetic hormone (AKH), AKH/corazonin
      related peptide (ACP), and corazonin from arthropods. We conclude that these G
      protein-coupled receptors (GPCRs) are closely related and have a common
      evolutionary origin, which dates back to the split of Proto- and Deuterostomia,
      about 700 million years ago. We propose that in the protostomian lineage, the
      ancestral GnRH-like receptor gene duplicated as did its GnRH-like ligand gene,
      followed by diversification, leading to (i) a corazonin receptor gene and a
      corazonin-like ligand gene, and (ii) an AKH receptor gene and an AKH-like ligand
      gene in the Mollusca and Annelida. Subsequently, the AKH receptor and ligand
      genes duplicated once more, yielding the situation that we know from arthropods
      today, where three independent hormonal systems exist, signalling with AKH, ACP,
      and corazonin. Our model for the evolution of GnRH signaling in the Protostomia
      is a striking example of receptor-ligand co-evolution. This model has been
      developed using several bioinformatics tools (TBLASTN searches, phylogenetic tree
      analyses), which also helped us to annotate six novel AKH preprohormones and
      their corresponding AKH sequences from the following molluscs: the sea hare
      Aplysia californica (AKH sequence: pQIHFSPDWGTamide), the sea slug Tritonia
      diomedea (pQIHFSPGWEPamide), the fresh water snail Bithynia siamensis
      goniomphalos (pQIHFTPGWGSamide), the owl limpet Lottia gigantea
      (pQIHFSPTWGSamide), the oyster Crassostrea gigas (pQVSFSTNWGSamide), and the
      freshwater pearl mussel Hyriopsis cumingii (pQISFSTNWGSamide). We also found AKHs
      in the tardigrade Hysibius dujardini (pQLSFTGWGHamide), the rotifer Brachionus
      calycifloros (pQLTFSSDWSGamide), and the penis worm Priapulus caudatus
      (pQIFFSKGWRGamide). This is the first report, showing that AKH signaling is
      widespread in molluscs. 

PMID- 25058365
TI  - Identification of the first neuropeptides from the Amphipoda (Arthropoda,
      Crustacea).
AB  - Despite being used as models in the field of ecotoxicology, including use in
      studies of endocrine disruption, little is known about the hormonal systems of
      amphipods, particularly their peptidergic signaling systems. Here, transcriptome
      shotgun assembly (TSA) sequences were used to predict the structures of the first
      neuropeptides from members of this crustacean order. Using a well-established
      workflow, BLAST searches of the extant amphipod TSA data were conducted for
      putative peptide-encoding transcripts. The pre/preprohormones deduced from the
      identified TSA sequences were then used to predict the mature structures of
      amphipod neuropeptides. In total, 43 putative peptide-encoding transcripts were
      identified from three amphipods, Echinogammarus veneris, Hyalella azteca and
      Melita plumulosa. Collectively, 139 distinct mature peptides (110 from E. veneris
      alone) were predicted from these TSA sequences. The identified peptides included
      members of the adipokinetic hormone/red pigment concentrating hormone,
      allatostatin A, allatostatin B, allatostatin C, bursicon alpha, bursicon beta,
      crustacean hyperglycemic hormone, diuretic hormone 31, FLRFamide, molt-inhibiting
      hormone, myosuppressin, neuroparsin, neuropeptide F, orcokinin, pigment
      dispersing hormone (PDH), proctolin, RYamide, SIFamide, sulfakinin and tachykinin
      related peptide families. Of particular note were the identifications of
      orcokinins possessing SFDEIDR- rather than the typical NFDEIDR- amino-termini,
      e.g. SFDEINRSNFGFN, a carboxyl-terminally amidated orcokinin, i.e.
      SFDEINRSNFGFSamide, PDHs longer than the stereotypical 18 amino acids, e.g.
      NSELLNTLLGSKSLAALRAAamide, and a 13 rather than 12 amino acid long SIFamide, i.e.
      GPYRKPPFNGSIFamide. These data not only provide the first descriptions of native
      amphipod neuropeptides, but also represent a new resource for initiating
      investigations of peptidergic signaling in the Amphipoda. 

PMID- 25058366
TI  - Involvement of melanin-concentrating hormone 2 in background color adaptation of
      barfin flounder Verasper moseri.
AB  - In teleosts, melanin-concentrating hormone (MCH) plays a key role in skin color
      changes. MCH is released into general circulation from the neurohypophysis, which
      causes pigment aggregation in the skin chromatophores. Recently, a novel MCH
      (MCH2) precursor gene, which is orthologous to the mammalian MCH precursor gene,
      has been identified in some teleosts using genomic data mining. The physiological
      function of MCH2 remains unclear. In the present study, we cloned the cDNA for
      MCH2 from barfin flounder, Verasper moseri. The putative prepro-MCH2 contains 25
      amino acids of MCH2 peptide region. Liquid chromatography-electrospray ionization
      mass spectrometry with a high resolution mass analyzer were used for confirming
      the amino acid sequences of MCH1 and MCH2 peptides from the pituitary extract. In
      vitro synthesized MCH1 and MCH2 induced pigment aggregation in a dose-dependent
      manner. A mammalian cell-based assay indicated that both MCH1 and MCH2
      functionally interacted with both the MCH receptor types 1 and 2. Mch1 and mch2
      are exclusively expressed in the brain and pituitary. The levels of brain mch2
      transcript were three times higher in the fish that were chronically acclimated
      to a white background than those acclimated to a black background. These results
      suggest that in V. moseri, MCH1 and MCH2 are involved in the response to changes
      in background colors, during the process of chromatophore control. 

PMID- 25058367
TI  - Oestrogen and insulin-like growth factors during the reproduction and growth of
      the tilapia Oreochromis niloticus and their interactions.
AB  - Oestrogens and insulin-like growth factors (Igfs) play both a central role in the
      regulation of reproduction and growth and can interact especially in species
      showing a clear-cut sex-linked growth dimorphism (SGD) like in tilapia. Aromatase
      is essential in ovarian differentiation and oogenesis since it controls oestrogen
      synthesis. During tilapia sex differentiation, aromatase cyp19a1a expression
      increases from 9 days post-fertilization (dpf), resulting in high oestradiol
      level. High temperature, exogenous androgens or aromatase inhibitors override
      genetic sex differentiation inducing testes development through the suppression
      of cyp19a1a gene expression and aromatase activity. Supplementation with 17beta
      oestradiol (E2) of gonadectomized juveniles induced a sustained and higher E2
      plasma level than in intact or gonadectomized controls and both sexes showed
      reduced growth. Juvenile and mature females treated with the aromatase inhibitor
      1,4,6-androstatriene-3,17-dione had 19% lower E2 plasma level compared to
      controls and they showed a 32% increased growth after 28 days of treatment.
      Altogether, these data suggest that E2 inhibits female growth leading to the SGD.
      Regarding Igf-1, mRNA and peptide appeared in liver at ~ 4 dpf and then in organs
      involved in growth and metabolism, indicating a role in early growth, metabolism
      and organogenesis. Gonad igf-1 showed an early expression and the peptide could
      be detected at ~ 7 dpf in somatic cells. It appeared in germ cells at the onset
      of ovarian (29 dpf) and testicular (52 dpf) meiosis. In testis, Igf-1 together
      with steroids may regulate spermatogenesis whereas in ovary it participates in
      steroidogenesis regulation. Igf-1 and Igf-2 promote proliferation of follicular
      cells and oocyte maturation. Igf-3 expression is gonad specific and localized in
      the ovarian granulosa or testicular interstitial cells. In developing gonads igf
      3 is up-regulated in males but down-regulated in females. In contrast, bream Gh
      injections increased igf-1 mRNA in male and female liver and ovaries but gonadal
      igf-3 was not affected. Thus, local Igf-1 and Igf-2 may play crucial roles in the
      formation, development and function of gonads while Igf-3 depending on the
      species is involved in male and female reproduction. Furthermore, precocious
      ethynylestradiol (EE) exposure induced lasting effects on growth, through
      pituitary gh inhibition, local suppression of igf-1 expression and in testis only
      down-regulation of igf-3 mRNA. In conclusion, SGD in tilapia may be driven
      through an inhibitory effect due to E2 synthesis in female and involving Igfs
      regulation.

PMID- 25058368
TI  - Coexistence of productive and non-productive populations by fluctuation-driven
      spatio-temporal patterns.
AB  - Cooperative interactions, their stability and evolution, provide an interesting
      context in which to study the interface between cellular and population levels of
      organization. Here we study a public goods model relevant to microorganism
      populations actively extracting a growth resource from their environment. Cells
      can display one of two phenotypes - a productive phenotype that extracts the
      resources at a cost, and a non-productive phenotype that only consumes the same
      resource. Both proliferate and are free to move by diffusion; growth rate and
      diffusion coefficient depend only weakly phenotype. We analyze the continuous
      differential equation model as well as simulate stochastically the full dynamics.
      We find that the two sub-populations, which cannot coexist in a well-mixed
      environment, develop spatio-temporal patterns that enable long-term coexistence
      in the shared environment. These patterns are purely fluctuation-driven, as the
      corresponding continuous spatial system does not display Turing instability. The
      average stability of coexistence patterns derives from a dynamic mechanism in
      which the producing sub-population equilibrates with the environmental resource
      and holds it close to an extinction transition of the other sub-population,
      causing it to constantly hover around this transition. Thus the ecological
      interactions support a mechanism reminiscent of self-organized criticality; power
      law distributions and long-range correlations are found. The results are
      discussed in the context of general pattern formation and critical behavior in
      ecology as well as in an experimental context. 

PMID- 25058369
TI  - Dengue and the world football cup: a matter of timing.

PMID- 25058370
TI  - Long lasting remission after haploidentical stem cell transplant and pre-emptive
      donor lymphocyte infusions in a patient with primary refractory Hodgkin lymphoma.

PMID- 25058371
TI  - Deacetylase inhibitors for the treatment of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a diverse group of myeloid disorders, with
      patients being at risk for cytopenias or progression to acute myeloid leukemia.
      Several classification and prognostic scoring systems have been developed. High
      intensity treatments are not appropriate for all patients. Two demethylating
      agents, azacitidine and decitabine, are approved for the treatment of MDS,
      although many patients do not derive long-term benefit and eventually progress.
      Deacetylase inhibitors have emerged as novel treatment candidates based on
      mechanistic rationale and preliminary data. This article reviews existing data on
      MDS treatment and discusses the rationale and potential for combination with
      deacetylase inhibitors. 

PMID- 25058372
TI  - Is survival in myeloid malignancies really improving? A retrospective 15-year
      population-based study.
AB  - Myeloid malignancies (MMs) are heterogeneous groups of diseases which present
      different prognoses. Using data from the population-based Girona Cancer Registry,
      we estimated the relative survival (RS) rates and relative excess risk of death
      among patients with MMs in the province of Girona between 1994 and 2008. The 5
      year RS rate was 49.7%, ranging from 20.2% for acute myeloid leukemia (AML) to
      75.3% for myeloproliferative neoplasms (MPN). Marked differences in RS were
      observed when the age of patients was considered: an increase in RS was mainly
      found in younger patients with myelodysplastic syndromes and MPN. Furthermore,
      cases of chronic myeloid leukemia treated with imatinib had a significantly
      better outcome compared with those that were untreated. Despite the slight
      improvement in the survival rate of younger patients with AML, RS remained stable
      for 15 years, as no significant improvements were made in the management of the
      disease during that period. 

PMID- 25058373
TI  - A novel TTC40-MSI2 fusion in de novo acute myeloid leukemia with an unbalanced
      10;17 translocation.

PMID- 25058374
TI  - Advances in umbilical cord blood transplant: an overview of the 12th
      International Cord Blood Symposium, San Francisco, 5-7 June 2014.
AB  - From 5 to 7 June the 12th Annual International Cord Blood Symposium was held in
      San Francisco. The meeting was devoted to advances in umbilical cord blood
      research with a major focus on translational and clinical results in cord blood
      transplant and in regenerative medicine. Over 3 days, a comprehensive summary of
      the state of the art was provided. We have summarized the most important data,
      organized around the following themes: use of umbilical cord blood for tissue
      repair, new indications for umbilical cord blood unit stem cell transplant (CBU
      SCT), enhancing count recovery after CBU SCT, improving outcomes, product quality
      and financial and cost considerations. 

PMID- 25058376
TI  - Deciphering complement interference in anti-human leukocyte antigen antibody
      detection with flow beads assays.
AB  - BACKGROUND: Anti-human leukocyte antigen (HLA) antibody detection in solid-phase
      flow beads assays can be quenched by complement activation, but the precise
      mechanism of this interference is not fully elucidated yet. METHODS: Using the
      Luminex flow beads screening assay for detection of anti-HLA antibodies, we
      analyzed the binding of high concentrations of the pan class I anti-HLA
      monoclonal antibody W6/32 in neat normal, ethylenediaminetetraacetic acid-treated
      normal and complement factors C1q, C4/C3, C2, C3, factor B or C5-depleted human
      sera, using anti-mouse immunoglobulin G as the detection antibody. Complement
      activation and binding to beads were revealed using anti-human C1q, C4d, and C3d
      antibodies. To translate our findings to the human setting, we used the class I
      and class II HLA single-antigen flow beads assays and sera from four patients
      with high titers of antibodies. RESULTS: Detection of W6/32 did not suffer any
      interference with C1q and C4/C3-depleted sera. A partial quenching was observed
      with C2, C3, and factor B-depleted sera, but was more pronounced with the factor
      B-depleted serum. W6/32 was undetectable in presence of C5-depleted serum. The
      binding of activation products derived from C3 principally, and also from C4,
      impaired immunoglobulin G and C1q detection. Accordingly, C4d detection was
      hindered by deposition of activated C3. Similar findings were obtained with
      patients' sera. CONCLUSION: Binding of C4 and C3 activation products is the main
      responsible for complement interference in flow beads assays. A complete
      quenching requires complement activation through C3 cleavage and its
      amplification by the alternative pathway.

PMID- 25058375
TI  - Relevance of the thyroid hormones-alphavbeta3 pathway in primary myeloma bone
      marrow cells and to bortezomib action.
AB  - Thyroid hormones (T3 and T4) induce proliferation in multiple myeloma (MM) cell
      lines via the alphavbeta3 integrin-mitogen-activated protein kinase (MAPK)
      pathway. We further show in primary MM bone marrow (BM) samples (n = 9) induction
      of cell viability by 1 nM T3 (13%, p < 0.002) and more potently by 100 nM T4 (21
      45%, p < 0.0002) and a quick (1 h) and long-lasting (24 h) pERK activation, which
      was inhibited in the presence of beta3 but not beta1 blocking antibodies.
      Involvement of the integrin was further shown by two disintegrins, Arg-Gly-Asp
      (RGD) and echistatin peptides, which occluded the effects of T3/T4 on viability,
      proliferating cell nuclear antigen (PCNA) (proliferation marker) and apoptotic
      gene expression. Lastly, T3/T4 significantly opposed bortezomib (25 nM)
      cytotoxicy, as confirmed by several methods. In summary, our results imply that
      endogenous thyroid hormones in myeloma are factors that may support cell growth,
      with relevance to bortezomib action. 

PMID- 25058377
TI  - Swelling of chemical and physical planar brushes of gradient copolymers in a
      selective solvent.
AB  - We propose a mean-field theory of chemical and physical planar brushes of linear
      gradient copolymers swollen in a selective solvent. The polymer chains are
      grafted to the substrate by the ends with the excess of insoluble monomer units,
      and the majority of the soluble units are located near the free ends of the
      chains. The grafting points are considered to be immobile (chemical brush) and
      mobile in-plane (physical brush). In the latter case the grafting density is
      determined from the equilibrium conditions (minimum of the free energy). A common
      peculiarity of the brushes of both types is that the polymer concentration
      gradually changes from a relatively high value near the substrate (collapsed
      region of the brush) to a small value near the free surface (swollen region of
      the brush). In the case of the chemical brush, a polymer depletion zone can
      appear in the middle of the brush if incompatibility between insoluble and
      soluble (A and B) units is high enough. Here the polymer density is even lower
      than near the free surface of the brush. The grafting density of the physical
      brush is inversely proportional to the chain length and increases with the
      decrease of the solvent quality for the insoluble (A) units. The latter can be
      accompanied by shrinkage of the brush thickness due to broad distribution of the
      insoluble units through the chain: a minor fraction of insoluble units near the
      free ends can aggregate with a major fraction of them near the substrate. As a
      result, the concentration of the soluble (B) units can have a maximum in the
      middle of the brush rather than near the free surface. 

PMID- 25058378
TI  - PINK1 deficiency sustains cell proliferation by reprogramming glucose metabolism
      through HIF1.
AB  - PTEN-induced kinase-1 (PINK1) is a Ser/Thr kinase implicated in familial early
      onset Parkinson's disease, and was first reported as a growth suppressor. PINK1
      loss-of-function compromises both mitochondrial autophagy and oxidative
      phosphorylation. Here we report that PINK1 deficiency triggers hypoxia-inducible
      factor-1alpha (HIF1alpha) stabilization in cultured Pink1(-/-) mouse embryonic
      fibroblasts and primary cortical neurons as well as in vivo. This effect,
      mediated by mitochondrial reactive oxygen species, led to the upregulation of the
      HIF1 target, pyruvate dehydrogenase kinase-1, which inhibits PDH activity.
      Furthermore, we show that HIF1alpha stimulates glycolysis in the absence of
      Pink1, and that the promotion of intracellular glucose metabolism by HIF1alpha
      stabilization is required for cell proliferation in Pink1(-/-) mice. We propose
      that loss of Pink1 reprograms glucose metabolism through HIF1alpha, sustaining
      increased cell proliferation. 

PMID- 25058379
TI  - Comparison of three different brushing techniques to isolate and culture primary
      nasal epithelial cells from human subjects.
AB  - PURPOSE: Primary nasal epithelial cells are used for diagnostic purposes in
      clinical routine and have been shown to be good surrogate models for bronchial
      epithelial cells in studies of airway inflammation and remodeling. We aimed at
      comparing different instruments allowing isolation of nasal epithelial cells.
      METHODS: Primary airway epithelial cell cultures were established using cells
      acquired from the inferior surface of the middle turbinate of both nostrils.
      Three different instruments to isolate nasal cells were used: homemade cytology
      brush, nasal swab, and curette. Cell count, viability, time until a confluent
      cell layer was reached, and success rate in establishing cell cultures were
      evaluated. A standard numeric pain intensity scale was used to assess the
      acceptability of each instrument. RESULTS: Sixty healthy adults (median with
      interquartile range [IQR] age of 31 [26-37] years) participated in the study.
      Higher number of cells (*10(5) cells/ml) was obtained using brushes (9.8 [5.9
      33.5]) compared to swabs (2.4 [1.5-3.9], p < 0.0001) and curettes (5.5 [4.4-6.9],
      p < 0.01). Cell viability was similar between groups. Cells obtained by brushes
      had the fastest growth rate, and the success rate in establishing primary cell
      cultures was highest with brushes (90% vs. 65% for swabs and 70% for curettes).
      Pain was highest with curettes (VAS score 4.0 [3.0-5.0] out of 10). The
      epithelial phenotype of the cultures was confirmed through cytokeratin and E
      cadherin staining. CONCLUSIONS: All three types of instruments allow collection
      and growth of human nasal epithelial cells with good acceptability to study
      participants. The most efficient instrument is the nasal brush.

PMID- 25058380
TI  - Live Related versus Cadaveric Limbal Allograft in Limbal Stem Cell Deficiency.
AB  - AIM: To compare outcomes of live related limbal allograft (Lr-CLAL) versus
      cadaveric keratolimbal allograft (KLAL) in limbal stem cell deficiency (LSCD)
      secondary to ocular burns. METHODS: Twenty patients with stage IIb LSCD were
      randomized so that cases underwent either Lr-CLAL or KLAL. Fibrovascular pannus
      was removed and superficial keratectomy done on the recipient bed. Limbal
      lenticule of 2-3 clock hours' length was harvested from the donor, which was
      placed over the host bed and sutured followed by bandage contact lens
      application. Parameters assessed were uncorrected visual acuity (UCVA), best
      corrected visual acuity (BCVA), conjunctivalization, corneal neovascularization,
      epithelial defects, corneal clarity, Schirmer's test, tear film breakup time
      (tBUT), and ultrasonic pachymetry. RESULTS: At 6 months follow-up, the Lr-CLAL
      group had a higher gain in vision (p = 0.029), decrease in conjunctivalization (p
      = 0.009), and increase in Schirmer's values (p = 0.009). CONCLUSION: Lr-CLAL
      seems to have better result in terms of vision gain and ocular surface
      restoration.

PMID- 25058381
TI  - Molecular dynamics simulations of histidine-containing cod antimicrobial peptide
      paralogs in self-assembled bilayers.
AB  - Gaduscidin-1 and -2 (GAD-1 and GAD-2) are antimicrobial peptides (AMPs) that
      contain several histidine residues and are thus expected to exhibit pH-dependent
      activity. In order to help elucidate their mechanism of membrane disruption, we
      have performed molecular dynamics simulations with the peptides in both histidine
      charged and histidine-neutral forms, along with 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) lipid molecules. The simulations employed GROMACS software
      and an OPLS-AA force field. Initially, the peptide and lipids were placed
      randomly in the simulation box and then were allowed to self-assemble. The
      results demonstrated a marked preference for the regions of the peptides that
      contain sequential pairs of histidine residues to associate closely with bilayer
      pores. This preference is observed even when the histidines are in their
      uncharged form. It appears that the relative compactness and rigidity of
      histidine pairs require the more aqueous and disordered environment of the pores
      to satisfy hydrophilic interactions. The final peptide structures exhibited a
      wide variety of structures and topologies, with the most helical structures
      positioning most parallel to the bilayer surface and the less ordered structures
      interacting more closely with the pore. Thus, the results give atomistic insight
      into those models of AMP mechanism that promote the importance of structural
      heterogeneity and imperfect amphipathicity to AMP activity and selectivity. 

PMID- 25058382
TI  - Haemoperitoneum: an extremely rare complication of leiomyoma.

PMID- 25058383
TI  - Effects of Jamaican bitter yam (Dioscorea polygonoides) and diosgenin on blood
      and fecal cholesterol in rats.
AB  - A sapogenin-rich preparation from Jamaican bitter yam (Dioscorea polygonoides)
      has been shown to reduce blood cholesterol concentrations in hypercholesterolemic
      rats and mice. Also, diosgenin supplementation has been reported to have
      antilipemic effects in several animal species. We investigated potential
      mechanisms of the lipid-lowering actions of bitter yam and also whether the
      actions were mediated by diosgenin. Sprague-Dawley rats were fed a
      hypercholesterolemic diet (4% cholesterol) alone or with 5% bitter yam or 1%
      diosgenin supplementation for 6 weeks. The control group was fed normal rat chow.
      The serum lipid profile, fecal cholesterol concentration, and serum lipase
      activity were assessed at the end of the period. The induction of
      hypercholesterolemia was inhibited by coadministration of 5% bitter yam or 1%
      diosgenin in the diet. Serum lipid profiles were similar in rats fed bitter yam
      or diosgenin. The fecal cholesterol concentration was significantly (P < .01)
      higher in rats fed diosgenin compared to the cholesterol group. However, there
      was no corresponding elevation in the group fed bitter yam. Administration of
      bitter yam or diosgenin supplement significantly increased (P < .01) the serum
      lipase activity compared to the normal control and cholesterol groups. The
      cholesterol-supplemented diet inhibited normal gain in body weight over the
      period. This action was potentiated by diosgenin. The effects of the respective
      supplements on body weight were not completely explained by food consumption.
      Supplementation of the diet with Jamaican bitter yam may be therapeutically
      beneficial in the management of hypercholesterolemia.

PMID- 25058384
TI  - Synergy of licorice extract and pea protein hydrolysate for oxidative stability
      of soybean oil-in-water emulsions.
AB  - Previously developed radical-scavenging pea protein hydrolysates (PPHs) prepared
      with Flavourzyme (Fla-PPH) and Protamex (Pro-PPH) were used as cosurfactants with
      Tween 20 to produce soybean oil-in-water (O/W) emulsions, and the suppression of
      lipid oxidation was investigated. Both PPHs significantly retarded oxidation (P <
      0.05) of the emulsions when stored at 37  degrees C for 14 days. Electron
      microscopy revealed an interfacial peptidyl membrane around oil droplets, which
      afforded steric restrictions to oxidation initiators. When licorice extract (LE)
      was also used in emulsion preparation, a remarkable synergistic oxidation
      inhibition was observed with both PPHs. LE adsorbed onto oil droplets either
      directly or through associating with PPH to produce a thick and compact
      interfacial membrane enabling the defense against oxygen species. Liquiritin
      apioside, neolicuroside, glabrene, and 18beta-glycyrrhetic acid were the
      predominant phenolic derivatives partitioning at the interface and most likely
      the major contributors to the notable synergistic antioxidant activity when
      coupled with PPHs. 

PMID- 25058386
TI  - How much exercise are older adults living in nursing homes doing in daily life? A
      cross-sectional study.
AB  - Information on the amount of exercise practised by nursing home (NH) residents is
      scarce. This study aimed at describing NH residents' participation in exercise
      classes, as well as to examine whether the presence of a professional exercise
      instructor in the facilities is associated with residents' exercise habits. The
      cross-sectional data of 5402 residents (median age = 88 years; mostly women
      (75.2%)) from 163 NHs in France were analysed. Adjusted logistic and linear
      regressions were performed to examine whether the presence of a professional
      exercise instructor in the NH was associated with exercise habits: exercise
      participation, frequency, duration, and levels. From the 5402 participants, 1914
      were participating in exercise classes provided in the NH. Most of them had an
      exercise frequency of 1x/week or less. Median duration of exercise sessions was
      45 min. Exercise levels were rated as: highly active (n = 487), intermediately
      active (n = 1096), and poorly active (n = 331). The presence of a professional
      exercise instructor working in the facility was significantly associated with
      exercise participation and with higher exercise frequencies and levels, and
      session duration. In conclusion, the presence of professional exercise
      instructors is associated with better exercise habits in NH residents. Improved
      exercise habits may potentially be translated into better health in this
      population.

PMID- 25058385
TI  - The emerging role of speckle-type POZ protein (SPOP) in cancer development.
AB  - Speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) is an E3
      ubiquitin ligase adaptor protein that is frequently mutated in prostate and
      endometrial cancers. All the cancer-associated SPOP mutations reported to date
      are clustered in the meprin and TRAF (Tumor necrosis factor receptor-associated
      factor) homology (MATH) domain, presumably affecting substrate binding. SPOP
      mutations in prostate cancer are mutually exclusive with the ETS (Erythroblast
      transformation-specific) family gene rearrangements and define a distinct
      molecular subclass of prostate cancer. SPOP mutations contribute to prostate
      cancer development by altering the steady-state levels of key components in the
      androgen-signaling pathway. 

PMID- 25058387
TI  - Cyclic-AMP-dependent protein kinase (PKA) activity assay based on FRET between
      cationic conjugated polymer and chromophore-labeled peptide.
AB  - A sensitive fluorescence turn-on biosensing platform for protein kinase activity
      assay has been developed based on fluorescence resonance energy transfer (FRET)
      between a fluorophore labeled peptide and a water soluble cationic conjugated
      polymer (CCP). The CCP-based assay is based on the electrostatic interaction
      between the peptide and the CCP. The FRET efficiency will change with the
      changing charges around the peptide after phosphorylation. The feasibility of
      this method has been demonstrated by sensitive measurement of the activity of
      cAMP-dependent protein kinase (PKA) with a low detection limit (0.3 mU MUL(-1)).
      Based on its simple mechanism, this assay is also sensitive and robust enough to
      be applied to the evaluation of PKA inhibitor H-89. The IC50 value, the half
      maximal inhibitory concentration, was 40 nM. Furthermore, our method has
      excellent selectivity. CCP-based assay is sensitive, versatile, cost-effective
      and easy to operate, so, this method is a promising candidate for kinase activity
      assay and inhibitor screening. 

PMID- 25058390
TI  - Noble-metal-free Fe-N/C catalyst for highly efficient oxygen reduction reaction
      under both alkaline and acidic conditions.
AB  - In this work, we report the synthesis and assessment of a new non-precious-metal
      oxygen reduction reaction (ORR) catalyst from pyrolysis of an iron-coordinated
      complex which manifests superior activity in both alkaline and acidic media.
      11,11'-bis(dipyrido[3,2-a:2',3'-c]phenazinyl) (bidppz) was selected as a ligand
      for the formation of a nitrogen-rich iron-coordinated coordination polymer (Fe
      bidppz) which forms a self-supporting catalyst containing high densities of
      nitrogen and iron doping by pyrolysis. The catalyst pyrolyzed at 800  degrees C
      (Fe-N/C-800) shows the highest ORR activity with onset and half-wave potentials
      of 923 and 809 mV in 0.1 M KOH, respectively, which are comparable to those of
      Pt/C (half-wave potential 818 mV vs RHE) at the same catalyst loading. Besides,
      the Fe-N/C-800 catalyst has an excellent ORR activity with onset and half-wave
      potentials only 38 and 59 mV less than those of the Pt/C catalyst in 0.1 M HClO4.
      The optimal Fe-N/C-800 catalyst displays much greater durability and tolerance of
      methanol than Pt/C. We propose that the Fe-N/C-800 catalyst has a considerably
      high density of surface active sites because Fe-N/C-800 possesses excellent ORR
      activity while its specific surface area is not so high. Electrochemical
      measurements show that the Fe-N/C-800 catalyst in KOH and HClO4 follows the
      effective four-electron-transfer pathway. 

PMID- 25058389
TI  - NAMPT is the cellular target of STF-31-like small-molecule probes.
AB  - The small-molecule probes STF-31 and its analogue compound 146 were discovered
      while searching for compounds that kill VHL-deficient renal cell carcinoma cell
      lines selectively and have been reported to act via direct inhibition of the
      glucose transporter GLUT1. We profiled the sensitivity of 679 cancer cell lines
      to STF-31 and found that the pattern of response is tightly correlated with
      sensitivity to three different inhibitors of nicotinamide
      phosphoribosyltransferase (NAMPT). We also performed whole-exome next-generation
      sequencing of compound 146-resistant HCT116 clones and identified a recurrent
      NAMPT-H191R mutation. Ectopic expression of NAMPT-H191R conferred resistance to
      both STF-31 and compound 146 in cell lines. We further demonstrated that both STF
      31 and compound 146 inhibit the enzymatic activity of NAMPT in a biochemical
      assay in vitro. Together, our cancer-cell profiling and genomic approaches
      identify NAMPT inhibition as a critical mechanism by which STF-31-like compounds
      inhibit cancer cells. 

PMID- 25058391
TI  - Screening of ROS1 rearrangements in lung adenocarcinoma by immunohistochemistry
      and comparison with ALK rearrangements.
AB  - ROS1 rearrangement is a predictive biomarker for response to the tyrosine kinase
      inhibitor, crizotinib. We investigated the usefulness of ROS1
      immunohistochemistry (IHC) for the detection of patients who harbor ROS1
      rearrangements in two separate cohorts. We also compared ROS1 IHC with ALK IHC in
      terms of diagnostic performance to predict each gene rearrangement. In a
      retrospective cohort, IHC was performed in 219 cases of lung adenocarcinoma with
      already known genetic alterations. In a prospective cohort, we performed IHC for
      111 consecutive cases of lung adenocarcinoma and confirmed the results by
      subsequent FISH. In the retrospective cohort, all 8 ROS1-rearranged tumors were
      immunoreactive, and 14 of 211 ROS1-wild cases were immunoreactive (sensitivity
      100% and specificity 93.4%). In the prospective cohort, all IHC-negative cases
      were FISH-negative, and 5 of 34 ROS1 immunoreactive cases were ROS1-rearranged
      (sensitivity 100% and specificity 72.6%). In ROS1-wild tumors, ROS1 protein was
      more expressed in the tumors of ever-smokers than in those of never-smokers (p =
      0.003). ALK IHC showed 100% sensitivity and 98.1 to 100% specificity in both
      patient cohorts. In conclusion, ROS1 IHC is highly sensitive, but less specific
      compared with ALK IHC for detection of the corresponding rearrangement. ROS1 IHC
      reactive tumors, especially when the tumor is stained with moderate to strong
      intensity or a diffuse pattern, are recommended to undergo FISH to confirm the
      gene rearrangement. 

PMID- 25058393
TI  - Dual-phase spinel MnCo2O4 and spinel MnCo2O4/nanocarbon hybrids for
      electrocatalytic oxygen reduction and evolution.
AB  - Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are essential
      reactions for energy-storage and -conversion devices relying on oxygen
      electrochemistry. High-performance, nonprecious metal-based hybrid catalysts are
      developed from postsynthesis integration of dual-phase spinel MnCo2O4 (dp
      MnCo2O4) nanocrystals with nanocarbon materials, e.g., carbon nanotube (CNT) and
      nitrogen-doped reduced graphene oxide (N-rGO). The synergic covalent coupling
      between dp-MnCo2O4 and nanocarbons effectively enhances both the bifunctional ORR
      and OER activities of the spinel/nanocarbon hybrid catalysts. The dp-MnCo2O4/N
      rGO hybrid catalysts exhibited comparable ORR activity and superior OER activity
      compared to commercial 30 wt % platinum supported on carbon black (Pt/C). An
      electrically rechargeable zinc-air battery using dp-MnCo2O4/CNT hybrid catalysts
      on the cathode was successfully operated for 64 discharge-charge cycles (or 768 h
      equivalent), significantly outperforming the Pt/C counterpart, which could only
      survive up to 108 h under similar conditions. 

PMID- 25058392
TI  - Plasma autoantibodies against heat shock protein 70, enolase 1 and
      ribonuclease/angiogenin inhibitor 1 as potential biomarkers for
      cholangiocarcinoma.
AB  - The diagnosis of cholangiocarcinoma (CCA) is often challenging, leading to poor
      prognosis. CCA arises via chronic inflammation which may be associated with
      autoantibodies production. This study aims to identify IgG antibodies directed at
      self-proteins and tumor-associated antigens. Proteins derived from immortalized
      cholangiocyte cell line (MMNK1) and CCA cell lines (M055, M214 and M139) were
      separated using 2-dimensional electrophoresis and incubated with pooled plasma of
      patients with CCA and non-neoplastic controls by immunoblotting. Twenty five
      immunoreactive spots against all cell lines-derived proteins were observed on
      stained gels and studied by LC-MS/MS. Among these, heat shock protein 70 (HSP70),
      enolase 1 (ENO1) and ribonuclease/angiogenin inhibitor 1 (RNH1) obtained the
      highest matching scores and were thus selected for further validation. Western
      blot revealed immunoreactivity against HSP70 and RNH1 in the majority of CCA
      cases and weakly in healthy individuals. Further, ELISA showed that plasma HSP70
      autoantibody level in CCA was significantly capable to discriminate CCA from
      healthy individuals with an area under the receiver operating characteristic
      curve of 0.9158 (cut-off 0.2630, 93.55% sensitivity and 73.91% specificity).
      Plasma levels of IgG autoantibodies against HSP70 were correlated with
      progression from healthy individuals to cholangitis to CCA (r = 0.679, P<0.001).
      In addition, circulating ENO1 and RNH1 autoantibodies levels were also
      significantly higher in cholangitis and CCA compared to healthy controls
      (P<0.05). Moreover, the combinations of HSP70, ENO1 or RNH1 autoantibodies
      positivity rates improved specificity to over 78%. In conclusion, plasma IgG
      autoantibodies against HSP70, ENO1 and RNH1 may represent new diagnostic markers
      for CCA. 

PMID- 25058395
TI  - Patterning and processes: how stomatal development defines physiological
      potential.
AB  - Stomata present an excellent opportunity for connecting scientific disciplines:
      they are governed by complex genetic controls and unique cell biology, while also
      possessing a large influence over plant productivity and relationships with the
      environment. For this reason, stomata have engaged scientists for many centuries
      and continue to be a central interest for many fields of research. Recent
      technological advances have enabled interdisciplinary studies of stomata that
      were previously out of reach, and as a result, we are beginning to realize new
      insights about stomatal biology that place them at the intersection of our
      changing world. This review is intended to describe these interdisciplinary
      connections, discuss the relevant scales at which they are having an influence,
      and highlight ways we can capitalize on such novel approaches. While we
      incorporate knowledge about molecular advances, this is not intended to be an
      extensive review of that field, but rather, we focus on how those systems inform
      plant physiology and are connected to global scales. 

PMID- 25058394
TI  - IthaGenes: an interactive database for haemoglobin variations and epidemiology.
AB  - Inherited haemoglobinopathies are the most common monogenic diseases, with
      millions of carriers and patients worldwide. At present, we know several hundred
      disease-causing mutations on the globin gene clusters, in addition to numerous
      clinically important trans-acting disease modifiers encoded elsewhere and a
      multitude of polymorphisms with relevance for advanced diagnostic approaches.
      Moreover, new disease-linked variations are discovered every year that are not
      included in traditional and often functionally limited locus-specific databases.
      This paper presents IthaGenes, a new interactive database of haemoglobin
      variations, which stores information about genes and variations affecting
      haemoglobin disorders. In addition, IthaGenes organises phenotype, relevant
      publications and external links, while embedding the NCBI Sequence Viewer for
      graphical representation of each variation. Finally, IthaGenes is integrated with
      the companion tool IthaMaps for the display of corresponding epidemiological data
      on distribution maps. IthaGenes is incorporated in the ITHANET community portal
      and is free and publicly available at http://www.ithanet.eu/db/ithagenes. 

PMID- 25058396
TI  - Impacts of high beta-galactosidase expression on central metabolism of
      recombinant Pichia pastoris GS115 using glucose as sole carbon source via (13)C
      metabolic flux analysis.
AB  - The yeast Pichia pastoris GS115 is a widely used microbial cell factory for the
      production of heterologous protein. In order to reveal the impacts of high
      heterologous protein expression on the central metabolism of Pichia pastoris
      GS115 using glucose as sole carbon source, we engineered a high beta
      galactosidase expression strain P. pastoris G1HL and a low expression control
      strain P. pastoris GHL through controlling the initiation strength of
      constitutive promoter pGAP. The carbon flux distributions in these two strains
      were quantified via (13)C metabolic flux analysis. Compared to the control
      strain, G1HL showed a lower growth rate, a higher flux through glycolysis
      pathway, a higher flux through pentose phosphate pathway, and a lower flux
      through by-products secretion pathway. The metabolic flux redistribution in G1HL
      was thought to compensate the increased redox cofactors and energy demands caused
      by the high protein expression. Although the fluxes through Krebs cycle in two
      engineered strains were almost the same, they were significantly lower than those
      in wild strain. The enhanced expression of beta-galactosidase by glutamate
      supplementation demonstrated the potential of P. pastoris GS115 to catabolize
      more carbon through the Krebs cycle for even higher protein expression. In
      conclusion, our work indicates that P. pastoris GS115 can readjusts the central
      metabolism for higher heterologous protein expression and provides strategies for
      strain development or process optimization for enhancing production of
      heterologous protein. 

PMID- 25058397
TI  - Copper-catalyzed hydrophosphinations of styrenes in water at room temperature.
AB  - Copper-catalyzed hydrophosphinations of styrenyl systems in water, at room
      temperature is herein reported, enabled by our 'designer' surfactant TPGS-750-M.
      This is an attractive alternative to the more common Pd and Pt catalyzed
      versions. 

PMID- 25058398
TI  - Digital microfluidic platform for human plasma protein depletion.
AB  - Many important biomarkers for disease diagnosis are present at low concentrations
      in human serum. These biomarkers are masked in proteomic analysis by highly
      abundant proteins such as human serum albumin (HSA) and immunoglobulins (IgGs)
      which account for up to 80% of the total protein content of serum. Traditional
      depletion methods using macro-scale LC-columns for highly abundant proteins
      involve slow separations which impart considerable dilution to the samples.
      Furthermore, most techniques lack the ability to process multiple samples
      simultaneously. We present a method of protein depletion using superparamagnetic
      beads coated in anti-HSA, Protein A, and Protein G, manipulated by digital
      microfluidics (DMF). The depletion process was capable of up to 95% protein
      depletion efficiency for IgG and HSA in 10 min for four samples simultaneously,
      which resulted in an approximately 4-fold increase in signal-to-noise ratio in
      MALDI-MS analysis for a low abundance protein, hemopexin. This rapid and
      automated method has the potential to greatly improve the process of biomarker
      identification. 

PMID- 25058399
TI  - Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16
      oncoprotein-induced HIF-1alpha, VEGF, and IL-8 expression and in vitro
      angiogenesis in non-small cell lung cancer cells.
AB  - BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV)-16 infection may be related
      to non-smoking associated lung cancer. Our previous studies have found that HPV
      16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor
      1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), and interleukin-8
      (IL-8) expression in non-small cell lung cancer (NSCLC) cells. In this study, we
      further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.
      METHODS: Human NSCLC cell lines, A549 and NCI-H460, were stably transfected with
      pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the
      expression of HIF-1alpha, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun
      proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by
      ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by
      human umbilical vein endothelial cells (HUVECs) tube formation assay. Co
      immunoprecipitation was performed to analyze the interaction between c-Jun and
      HIF-1alpha. RESULTS: HPV-16 E6 and E7 oncoproteins promoted the activation of
      Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited
      HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of
      HIF-1alpha, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by
      specific siRNA abolished HPV-16 oncoprotein-induced HIF-1alpha, VEGF, and IL-8
      expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted
      HIF-1alpha protein stability via blocking proteasome degradation pathway, but c
      Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased
      the quantity of c-Jun binding to HIF-1alpha. CONCLUSIONS: PI3K/Akt signaling
      pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1alpha, VEGF,
      and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins
      promoted HIF-1alpha protein stability possibly through enhancing the interaction
      between c-Jun and HIF-1alpha, thus making a contribution to angiogenesis in NSCLC
      cells.

PMID- 25058400
TI  - Transmission and control of Plasmodium knowlesi: a mathematical modelling study.
AB  - INTRODUCTION: Plasmodium knowlesi is now recognised as a leading cause of malaria
      in Malaysia. As humans come into increasing contact with the reservoir host (long
      tailed macaques) as a consequence of deforestation, assessing the potential for a
      shift from zoonotic to sustained P. knowlesi transmission between humans is
      critical. METHODS: A multi-host, multi-site transmission model was developed,
      taking into account the three areas (forest, farm, and village) where
      transmission is thought to occur. Latin hypercube sampling of model parameters
      was used to identify parameter sets consistent with possible prevalence in
      macaques and humans inferred from observed data. We then explore the consequences
      of increasing human-macaque contact in the farm, the likely impact of rapid
      treatment, and the use of long-lasting insecticide-treated nets (LLINs) in
      preventing wider spread of this emerging infection. RESULTS: Identified model
      parameters were consistent with transmission being sustained by the macaques with
      spill over infections into the human population and with high overall basic
      reproduction numbers (up to 2267). The extent to which macaques forage in the
      farms had a non-linear relationship with human infection prevalence, the highest
      prevalence occurring when macaques forage in the farms but return frequently to
      the forest where they experience higher contact with vectors and hence sustain
      transmission. Only one of 1,046 parameter sets was consistent with sustained
      human-to-human transmission in the absence of macaques, although with a low human
      reproduction number (R(0H) = 1.04). Simulations showed LLINs and rapid treatment
      provide personal protection to humans with maximal estimated reductions in human
      prevalence of 42% and 95%, respectively. CONCLUSION: This model simulates
      conditions where P. knowlesi transmission may occur and the potential impact of
      control measures. Predictions suggest that conventional control measures are
      sufficient at reducing the risk of infection in humans, but they must be actively
      implemented if P. knowlesi is to be controlled.

PMID- 25058401
TI  - A biomaterial model of tumor stromal microenvironment promotes mesenchymal
      morphology but not epithelial to mesenchymal transition in epithelial cells.
AB  - The stromal tissue surrounding most carcinomas is comprised of an extracellular
      matrix densely packed with collagen-I fibers, which are often highly aligned in
      metastatic disease. Here we developed an in vitro model to test the effect of an
      aligned fibrous environment on cancer cell morphology and behavior, independent
      of collagen ligand presentation. We grew cells on a biomimetic surface of aligned
      electrospun poly-l-lactic acid (PLLA) fibers and then examined the effect of this
      environment on growth rate, morphology, cytoskeletal organization, biochemical
      and genetic markers of epithelial to mesenchymal transition (EMT), cell surface
      adhesion, and cell migration. We grew a phenotypically normal breast epithelial
      cell line (MCF10A) and an invasive breast cancer cell line (MDA-MB-231) on three
      different substrates: typical flat culture surface (glass or plastic), flat PLLA
      (glass coated with PLLA) or electrospun PLLA fibers. Cells of both types adopted
      a more mesenchymal morphology when grown on PLLA fibers, and this effect was
      exaggerated in the more metastatic-like MDA-MB-231 cells. However, neither cell
      type underwent the changes in gene expression indicative of EMT despite the
      changes in cell shape, nor did they exhibit the decreased adhesive strength or
      increased migration typical of metastatic cells. These results suggest that
      changes in cell morphology alone do not promote a more mesenchymal phenotype and
      consequently that the aligned fibrous environment surrounding epithelial cancers
      may not promote EMT solely through topographical cues. 

PMID- 25058402
TI  - Mesenchymal stroma cells trigger early attraction of M1 macrophages and
      endothelial cells into fibrin hydrogels, stimulating long bone healing without
      long-term engraftment.
AB  - Implantation of mesenchymal stroma cells (MSCs) is an attractive approach to
      stimulate closure of large bone defects but an optimal carrier has yet to be
      defined. MSCs may display trophic and/or immunomodulatory features or stimulate
      bone healing by their osteogenic activity. The aim of this study was to unravel
      whether fibrin hydrogel supports early actions of implanted MSCs, such as host
      cell recruitment, immunomodulation and tissue regeneration, in long bone defects.
      Female rats received cell-free fibrin or male MSCs embedded in a fibrin carrier
      into plate-stabilized femoral bone defects. Removed callus was analyzed for host
      cell invasion (day 6), local cytokine expression (days 3 and 6) and persistence
      of male MSCs (days 3, 6, 14 and 28). Fibrin-MSC composites triggered fast
      attraction of host cells into the hydrogel while cell-free fibrin implants were
      not invaded. A migration front dominated by M1 macrophages and endothelial
      progenitor cells formed while M2 macrophages remained sparse. Only MSC-seeded
      fibrin hydrogel stimulated early tissue maturation and primitive vessel formation
      at day 6 in line with significantly higher VEGF mRNA levels recorded at day 3.
      Local TNF-alpha, IL-1beta and IL-10 expression indicated a balanced immune cell
      activity independent of MSC implantation. Implanted MSCs persisted until day 14
      but not day 28. Our results demonstrate that fibrin hydrogel is an attractive
      carrier for MSC implantation into long bone defects, supporting host cell
      attraction and pro-angiogenic activity. By this angiogenesis, implant integration
      and tissue maturation was stimulated in long bone healing independent of long
      term engraftment of implanted MSCs. 

PMID- 25058403
TI  - Residential treatment for combat-related posttraumatic stress disorder:
      identifying trajectories of change and predictors of treatment response.
AB  - BACKGROUND: Combat-related posttraumatic stress disorder (PTSD) can be a
      difficult condition to treat and has been associated with serious medical and
      economic issues among U.S. military veterans. Distinguishing between treatment
      responders vs. non-responders in this population has become an important public
      health priority. This study was conducted to identify pre-treatment
      characteristics of U.S. veterans with combat-related PTSD that might contribute
      to favorable and unfavorable responses to high value treatments for this
      condition. METHOD: This study focused on 805 patients who completed a VHA PTSD
      residential program between 2000 and 2007. These patients completed the PTSD
      Clinical Checklist at pre-treatment, post-treatment, and a four-month follow-up
      assessment. Latent growth curve analysis (LCGA) was incorporated to determine
      trajectories of changes in PTSD across these assessments and whether several key
      clinical concerns for this population were associated with their treatment
      responses. STUDY FINDINGS: LCGA indicated three distinct trajectories in PTSD
      outcomes and identified several clinical factors that were prospectively linked
      with changes in veterans' posttraumatic symptomatology. When compared to a group
      with high PTSD symptom severity that decreased over the program but relapsed at
      follow-up (41%), the near half (48.8%) of the sample with an improving trajectory
      had less combat exposure and superior physical/mental health. However, when
      compared to a minority (10.2%) with relatively low symptomatology that also
      remained somewhat stable, patients in the improving group were younger and also
      reported greater combat exposure, poorer physical/mental health status, and more
      problems with substance abuse before the start of treatment. CONCLUSIONS:
      Findings suggest that veterans are most likely to benefit from residential
      treatment in an intermediate range of symptoms and risk factors, including PTSD
      symptom severity, history of combat exposure, and comorbid issues with
      physical/mental health. Addressing these factors in an integrative manner could
      help to optimize the effectiveness of treatments of combat-related PTSD in many
      cases.

PMID- 25058404
TI  - Novel insect leaf-mining after the end-Cretaceous extinction and the demise of
      cretaceous leaf miners, Great Plains, USA.
AB  - Plant and associated insect-damage diversity in the western U.S.A. decreased
      significantly at the Cretaceous-Paleogene (K-Pg) boundary and remained low until
      the late Paleocene. However, the Mexican Hat locality (ca. 65 Ma) in southeastern
      Montana, with a typical, low-diversity flora, uniquely exhibits high damage
      diversity on nearly all its host plants, when compared to all known local and
      regional early Paleocene sites. The same plant species show minimal damage
      elsewhere during the early Paleocene. We asked whether the high insect damage
      diversity at Mexican Hat was more likely related to the survival of Cretaceous
      insects from refugia or to an influx of novel Paleocene taxa. We compared damage
      on 1073 leaf fossils from Mexican Hat to over 9000 terminal Cretaceous leaf
      fossils from the Hell Creek Formation of nearby southwestern North Dakota and to
      over 9000 Paleocene leaf fossils from the Fort Union Formation in North Dakota,
      Montana, and Wyoming. We described the entire insect-feeding ichnofauna at
      Mexican Hat and focused our analysis on leaf mines because they are typically
      host-specialized and preserve a number of diagnostic morphological characters.
      Nine mine damage types attributable to three of the four orders of leaf-mining
      insects are found at Mexican Hat, six of them so far unique to the site. We found
      no evidence linking any of the diverse Hell Creek mines with those found at
      Mexican Hat, nor for the survival of any Cretaceous leaf miners over the K-Pg
      boundary regionally, even on well-sampled, surviving plant families. Overall, our
      results strongly relate the high damage diversity on the depauperate Mexican Hat
      flora to an influx of novel insect herbivores during the early Paleocene,
      possibly caused by a transient warming event and range expansion, and indicate
      drastic extinction rather than survivorship of Cretaceous insect taxa from
      refugia. 

PMID- 25058406
TI  - Traumatic prepapillary loop torsion and associated branch retinal artery
      occlusion.

PMID- 25058405
TI  - Nitric oxide affects ERK signaling through down-regulation of MAP kinase
      phosphatase levels during larval development of the ascidian Ciona intestinalis.
AB  - In the ascidian Ciona intestinalis larval development and metamorphosis require a
      complex interplay of events, including nitric oxide (NO) production, MAP kinases
      (ERK, JNK) and caspase-3 activation. We have previously shown that NO levels
      affect the rate of metamorphosis, regulate caspase activity and promote an
      oxidative stress pathway, resulting in protein nitration. Here, we report that NO
      down-regulates MAP kinase phosphatases (mkps) expression affecting positively ERK
      signaling. By pharmacological approach, we observed that the reduction of
      endogenous NO levels caused a decrease of ERK phosphorylation, whereas increasing
      levels of NO induced ERK activation. We have also identified the ERK gene network
      affected by NO, including mpk1, mpk3 and some key developmental genes by
      quantitative gene expression analysis. We demonstrate that NO induces an ERK
      independent down-regulation of mkp1 and mkp3, responsible for maintaining the ERK
      phosphorylation levels necessary for transcription of key metamorphic genes, such
      as the hormone receptor rev-erb and the van willebrand protein vwa1c. These
      results add new insights into the role played by NO during larval development and
      metamorphosis in Ciona, highlighting the cross-talk between different signaling
      pathways. 

PMID- 25058407
TI  - Comprehensive and Scalable Highly Automated MS-Based Proteomic Workflow for
      Clinical Biomarker Discovery in Human Plasma.
AB  - Over the past decade, mass spectrometric performance has greatly improved in
      terms of sensitivity, dynamic range, and speed. By contrast, only limited
      progress has been accomplished with regard to automation, throughput, and
      robustness of the proteomic sample preparation process upstream of mass
      spectrometry. The present work delivers an optimized analysis of human plasma
      samples in both small preclinical and large clinical studies, enabled by the
      development of a highly automated quantitative proteomic workflow. Several
      iterative evaluation and validation steps were performed before process "design
      freeze" and development completion. A robotic liquid handling workflow and
      platform (including reduction, alkylation, digestion, TMT labeling, pooling, and
      purification) were shown to provide better quantitative trueness and precision
      than manual operation at the bench. Depletion of the most abundant human plasma
      proteins and subsequent buffer exchange were also developed and integrated.
      Finally, 96 identical pooled human plasma samples were prepared in a 96-well
      plate format, and each sample was individually subjected to our developed
      workflow. This test revealed increased throughput and robustness compared with to
      date published manual or less automated workflows. Our workflow is ready-to-use
      for future (pre-) clinical studies. We expect our work to facilitate, accelerate,
      and improve clinical proteomic discovery in human blood plasma.

PMID- 25058408
TI  - Bioengineering of lanthipeptides in Escherichia coli: assessing the specificity
      of lichenicidin and haloduracin biosynthetic machinery.
AB  - The lichenicidin and haloduracin biosynthetic machinery specificity was
      investigated in vivo in Escherichia coli. Unlike previous reports using different
      hosts, it was found that the biosynthetic machineries of lichenicidin and
      haloduracin are highly specific to their dedicated peptide precursors. Likewise,
      the substitution of lichenicidin structural genes by chimeras of lichenicidin
      leader sequences and haloduracin core peptides did not yield mature haloduracin
      peptides. Despite these restrictions, it was found that the bifunctional enzyme
      HalT was able to process and export lichenicidin peptides. These findings
      corroborate the promiscuity of LanT enzymes reported for other lantibiotics, such
      as nukacin ISK-1 and lacticin 481. 

PMID- 25058409
TI  - Abnormal oxidative stress responses in fibroblasts from preeclampsia infants.
AB  - BACKGROUND: Signs of severe oxidative stress are evident in term placentae of
      infants born to mothers with preeclampsia (PE), but it is unclear whether this is
      a cause or consequence of the disease. Here fibroblast lines were established
      from umbilical cords (UC) delivered by mothers who had experienced early onset PE
      and from controls with the goal of converting these primary cells to induced
      pluripotent stem cells and ultimately trophoblast. Contrary to expectations, the
      oxidative stress responses of these non-placental cells from PE infants were more
      severe than those from controls. METHODS AND FINDINGS: Three features suggested
      that UC-derived fibroblasts from PE infants responded less well to oxidative
      stressors than controls: 1) While all UC provided outgrowths in 4% O2, success
      was significantly lower for PE cords in 20% O2; 2) PE lines established in 4% O2
      proliferated more slowly than controls when switched to 20% O2; 3) PE lines were
      more susceptible to the pro-oxidants diethylmaleate and tert-butylhydroquinone
      than control lines, but, unlike controls, were not protected by glutathione.
      Transcriptome profiling revealed only a few genes differentially regulated
      between PE lines and controls in 4% O2 conditions. However, a more severely
      stressed phenotype than controls, particularly in the unfolded protein response,
      was evident when PE lines were switched suddenly to 20% O2, thus confirming the
      greater sensitivity of the PE fibroblasts to acute changes in oxidative stress.
      CONCLUSIONS: UC fibroblasts derived from PE infants are intrinsically less able
      to respond to acute oxidative stress than controls, and this phenotype is
      retained over many cell doublings. Whether the basis of this vulnerability is
      genetic or epigenetic and how it pertains to trophoblast development remains
      unclear, but this finding may provide a clue to the basis of the early onset,
      usually severe, form of PE.

PMID- 25058411
TI  - Speaking two languages at once: unconscious native word form access in second
      language production.
AB  - Bilingualism research has established language non-selective lexical access in
      comprehension. However, the evidence for such an effect in production remains
      sparse and its neural time-course has not yet been investigated. We demonstrate
      that German-English bilinguals performing a simple picture-naming task
      exclusively in English spontaneously access the phonological form of -unproduced-
      German words. Participants were asked to produce English adjective-noun sequences
      describing the colour and identity of familiar objects presented as line
      drawings. We associated adjective and picture names such that their onsets
      phonologically overlapped in English (e.g., green goat), in German through
      translation (e.g., blue flower - 'blaue Blume'), or in neither language. As
      expected, phonological priming in English modulated event-related brain
      potentials over the frontocentral scalp region from around 440ms after picture
      onset. Phonological priming in German was detectable even earlier, from 300ms,
      even though German was never produced and in the absence of an interaction
      between language and phonological repetition priming at any point in time.
      Overall, these results establish the existence of non-selective access to
      phonological representations of the two languages in the domain of speech
      production. 

PMID- 25058410
TI  - Cuba: exploring the history of admixture and the genetic basis of pigmentation
      using autosomal and uniparental markers.
AB  - We carried out an admixture analysis of a sample comprising 1,019 individuals
      from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry
      Informative Markers (AIMs) to estimate the admixture proportions. We also
      characterized a number of haplogroup diagnostic markers in the mtDNA and Y
      chromosome in order to evaluate admixture using uniparental markers. Finally, we
      analyzed the association of 16 single nucleotide polymorphisms (SNPs) with
      quantitative estimates of skin pigmentation. In the total sample, the average
      European, African and Native American contributions as estimated from autosomal
      AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed
      relatively higher African and Native American contributions than the Western
      provinces. In particular, the highest proportion of African ancestry was observed
      in the provinces of Guantanamo (40%) and Santiago de Cuba (39%), and the highest
      proportion of Native American ancestry in Granma (15%), Holguin (12%) and Las
      Tunas (12%). We found evidence of substantial population stratification in the
      current Cuban population, emphasizing the need to control for the effects of
      population stratification in association studies including individuals from Cuba.
      The results of the analyses of uniparental markers were concordant with those
      observed in the autosomes. These geographic patterns in admixture proportions are
      fully consistent with historical and archaeological information. Additionally, we
      identified a sex-biased pattern in the process of gene flow, with a substantially
      higher European contribution from the paternal side, and higher Native American
      and African contributions from the maternal side. This sex-biased contribution
      was particularly evident for Native American ancestry. Finally, we observed that
      SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with
      melanin levels in the sample. 

PMID- 25058412
TI  - Differential effect of one versus two hands on visual processing.
AB  - Hand position in the visual field influences performance in several visual tasks.
      Recent theoretical accounts have proposed that hand position either (a)
      influences the allocation of spatial attention, or (b) biases processing toward
      the magnocellular visual pathway. Comparing these accounts is difficult as some
      studies manipulate the distance of one hand in the visual field while others vary
      the distance of both hands, and it is unclear whether single and dual hand
      manipulations have the same impact on perception. We ask if hand position affects
      the spatial distribution of attention, with a broader distribution of attention
      when both hands are near a visual display and a narrower distribution when one
      hand is near a display. We examined the effects of four hand positions near the
      screen (left hand, right hand, both hands, no hands) on both temporal and spatial
      discrimination tasks. Placing two hands near the display compared to two hands
      distant resulted in improved sensitivity for the temporal task and reduced
      sensitivity in the spatial task, replicating previous results. However, the
      single hand manipulations showed the opposite pattern of results. Together these
      results suggest that visual attention is focused on the graspable space for a
      single hand, and expanded when two hands frame an area of the visual field. 

PMID- 25058413
TI  - Becoming a written word: eye movements reveal order of acquisition effects
      following incidental exposure to new words during silent reading.
AB  - We know that from mid-childhood onwards most new words are learned implicitly via
      reading; however, most word learning studies have taught novel items explicitly.
      We examined incidental word learning during reading by focusing on the well
      documented finding that words which are acquired early in life are processed more
      quickly than those acquired later. Novel words were embedded in meaningful
      sentences and were presented to adult readers early (day 1) or later (day 2)
      during a five-day exposure phase. At test adults read the novel words in
      semantically neutral sentences. Participants' eye movements were monitored
      throughout exposure and test. Adults also completed a surprise memory test in
      which they had to match each novel word with its definition. Results showed a
      decrease in reading times for all novel words over exposure, and significantly
      shorter [corrected] total reading times at test for early than late novel words.
      Early-presented novel words were also remembered better in the offline test. Our
      results show that order of presentation influences processing time early in the
      course of acquiring a new word, consistent with partial and incremental growth in
      knowledge occurring as a function of an individual's experience with each word.

PMID- 25058414
TI  - Syntax and intentionality: an automatic link between language and theory-of-mind.
AB  - Three studies provided evidence that syntax influences intentionality judgments.
      In Experiment 1, participants made either speeded or unspeeded intentionality
      judgments about ambiguously intentional subjects or objects. Participants were
      more likely to judge grammatical subjects as acting intentionally in the speeded
      relative to the reflective condition (thus showing an intentionality bias), but
      grammatical objects revealed the opposite pattern of results (thus showing an
      unintentionality bias). In Experiment 2, participants made an intentionality
      judgment about one of the two actors in a partially symmetric sentence (e.g.,
      "John exchanged products with Susan"). The results revealed a tendency to treat
      the grammatical subject as acting more intentionally than the grammatical object.
      In Experiment 3 participants were encouraged to think about the events that such
      sentences typically refer to, and the tendency was significantly reduced. These
      results suggest a privileged relationship between language and central theory-of
      mind concepts. More specifically, there may be two ways of determining
      intentionality judgments: (1) an automatic verbal bias to treat grammatical
      subjects (but not objects) as intentional (2) a deeper, more careful
      consideration of the events typically described by a sentence. 

PMID- 25058415
TI  - Quasi-planar aromatic B36 and B36(-) clusters: all-boron analogues of coronene.
AB  - Flat boron has recently emerged as a fascinating concept in cluster science. Here
      we present computational evidence for the quasi-planar all-boron aromatic B36
      (C6v, (1)A1) and B36(-) (C2v, (2)A1) clusters, established as the global-minimum
      structures on the basis of Stochastic Surface Walking (SSW) searches. The
      energetics for low-lying isomeric structures are evaluated using the validated
      density-functional method at the PBE0/6-311+G* level. Our global-minimum
      structures are in line with a recent report (Z. A. Piazza et al., Nat. Commun.,
      2014, 5, 3113). These structures consist of two-dimensional close-packing boron
      with a perfect hexagonal hole at the center, which may serve as molecular models
      for the monolayer boron alpha sheet. Chemical bonding analysis indicates that B36
      and B36(-) are all-boron analogues of coronene (C24H12), featuring concentric
      dual pi aromaticity with an inner pi sextet and an outer pi sextet. The
      hydrogenated B36H6 (C6v, (1)A1) model cluster shows similar bonding properties,
      which possesses concentric triple aromaticity with inner pi, outer pi, and outer
      sigma sextets. 

PMID- 25058416
TI  - Including pathogen risk in life cycle assessment of wastewater management. 2.
      Quantitative comparison of pathogen risk to other impacts on human health.
AB  - Resource recovery from sewage sludge has the potential to save natural resources,
      but the potential risks connected to human exposure to heavy metals, organic
      micropollutants, and pathogenic microorganisms attract stakeholder concern. The
      purpose of the presented study was to include pathogen risks to human health in
      life cycle assessment (LCA) of wastewater and sludge management systems, as this
      is commonly omitted from LCAs due to methodological limitations. Part 1 of this
      article series estimated the overall pathogen risk for such a system with
      agricultural use of the sludge, in a way that enables the results to be
      integrated in LCA. This article (part 2) presents a full LCA for two model
      systems (with agricultural utilization or incineration of sludge) to reveal the
      relative importance of pathogen risk in relation to other potential impacts on
      human health. The study showed that, for both model systems, pathogen risk can
      constitute an important part (in this study up to 20%) of the total life cycle
      impacts on human health (expressed in disability adjusted life years) which
      include other important impacts such as human toxicity potential, global warming
      potential, and photochemical oxidant formation potential. 

PMID- 25058417
TI  - Mycoplasma pneumoniae CARDS toxin exacerbates ovalbumin-induced asthma-like
      inflammation in BALB/c mice.
AB  - Mycoplasma pneumoniae causes a range of airway and extrapulmonary pathologies in
      humans. Clinically, M. pneumoniae is associated with acute exacerbations of human
      asthma and a worsening of experimentally induced asthma in mice. Recently, we
      demonstrated that Community Acquired Respiratory Distress Syndrome (CARDS) toxin,
      an ADP-ribosylating and vacuolating toxin synthesized by M. pneumoniae, is
      sufficient to induce an asthma-like disease in BALB/cJ mice. To test the
      potential of CARDS toxin to exacerbate preexisting asthma, we examined
      inflammatory responses to recombinant CARDS toxin in an ovalbumin (OVA) murine
      model of asthma. Differences in pulmonary inflammatory responses between
      treatment groups were analyzed by histology, cell differentials and changes in
      cytokine and chemokine concentrations. Additionally, assessments of airway
      hyperreactivity were evaluated through direct pulmonary function measurements.
      Analysis of histology revealed exaggerated cellular inflammation with a strong
      eosinophilic component in the CARDS toxin-treated group. Heightened T-helper type
      2 inflammatory responses were evidenced by increased expression of IL-4, IL-13,
      CCL17 and CCL22 corresponding with increased airway hyperreactivity in the CARDS
      toxin-treated mice. These data demonstrate that CARDS toxin can be a causal
      factor in the worsening of experimental allergic asthma, highlighting the
      potential importance of CARDS toxin in the etiology and exacerbation of human
      asthma. 

PMID- 25058418
TI  - Web-based computational chemistry education with CHARMMing III: Reduction
      potentials of electron transfer proteins.
AB  - A module for fast determination of reduction potentials, E degrees , of redox
      active proteins has been implemented in the CHARMM INterface and Graphics
      (CHARMMing) web portal (www.charmming.org). The free energy of reduction, which
      is proportional to E degrees , is composed of an intrinsic contribution due to
      the redox site and an environmental contribution due to the protein and solvent.
      Here, the intrinsic contribution is selected from a library of pre-calculated
      density functional theory values for each type of redox site and redox couple,
      while the environmental contribution is calculated from a crystal structure of
      the protein using Poisson-Boltzmann continuum electrostatics. An accompanying
      lesson demonstrates a calculation of E degrees . In this lesson, an ionizable
      residue in a [4Fe-4S]-protein that causes a pH-dependent E degrees  is
      identified, and the E degrees  of a mutant that would test the identification is
      predicted. This demonstration is valuable to both computational chemistry
      students and researchers interested in predicting sequence determinants of E
      degrees  for mutagenesis. 

PMID- 25058419
TI  - Root biomass production in populations of six rooted macrophytes in response to
      Cu exposure: intra-specific variability versus constitutive-like tolerance.
AB  - Intra-specific variability of root biomass production (RP) of six rooted
      macrophytes, i.e. Juncus effusus, Phragmites australis, Schoenoplectus lacustris,
      Typha latifolia, Phalaris arundinacea, and Iris pseudacorus grown from clones, in
      response to Cu exposure was investigated. Root biomass production varied widely
      for all these macrophytes in control conditions (0.08 MUM) according to the
      sampling site. Root biomass production of T. latifolia and I. pseudacorus in the
      2.5-25 MUM Cu range depended on the sampling location but not on the Cu dose in
      the growth medium. For P. australis, J. effusus, S. lacustris, and P.
      arundinacea, an intra-specific variability of RP depending on both the sampling
      location and the Cu-dose was evidenced. This intra-specific variability of RP
      depending on the sampling location and of Cu-tolerance for these last four
      species suggests that Cu constitutive tolerance for all rooted macrophytes is not
      a species-wide trait but it exhibits variability for some species. 

PMID- 25058420
TI  - Distribution of perfluoroalkyl substances (PFASs) with isomer analysis among the
      tissues of aquatic organisms in Taihu Lake, China.
AB  - The distribution of perfluoroalkyl substances (PFASs) and the isomers of
      perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) was investigated
      among various tissues (including muscle, gill, kidney, liver) and eggs, in
      aquatic organisms in Taihu Lake, China. Highest concentration of SigmaPFASs was
      mostly found in liver (278-685 ng/g ww) and eggs (66.0-467 ng/g ww) while the
      lowest was in muscle (40.6-165 ng/g ww). n-PFOS was the predominant PFOS isomer
      in most of the tissues with a proportion of 46.3-96.5%. Ratios of PFAS
      concentrations in eggs to those in liver (E/L) increased positively with the
      protein-water partition coefficient. The E/L of PFOS isomers descended in the
      order: linear > monomethyl > diperfluoromethyl isomers. The liver/muscle and
      kidney/muscle ratios of n-PFOS were higher than branched isomers, suggesting that
      n-PFOS has higher binding affinity with hepatic proteins or branched isomers are
      preferentially excreted though liver and kidney. 

PMID- 25058421
TI  - Development of a passive sampler for Zinc(II) in urban pond waters using a
      polymer inclusion membrane.
AB  - The use of a polymer inclusion membrane (PIM) in a novel passive sampler to
      measure the time-weighted average concentration of Zn(II) in urban waters is
      described. The passive sampler consists of a compartment containing an acidic
      receiving solution, which is separated from the external source solution by a PIM
      consisting of 40 wt% di-2-(ethylhexyl) phosphoric acid as the extractant, and 60
      wt% poly-(vinyl chloride) as the base polymer. Two laboratory passive sampling
      techniques were tested. One involved immersion of the passive sampler into a
      source solution ("dip-in" approach) for a predetermined period of time while in
      the other one the source solution was flown past the membrane of the sampler
      ("flow-through" approach). The latter approach was found to be more suitable for
      the calibration of the passive sampler under laboratory conditions. A successful
      application using the "dip-in" sampling approach in urban waters has been
      conducted for proof of concept. 

PMID- 25058423
TI  - A new posttranslational regulation of REDD1/DDIT4 through cleavage by caspase 3
      modifies its cellular function.

PMID- 25058422
TI  - Vitamin A dimers trigger the protracted death of retinal pigment epithelium
      cells.
AB  - Cellular events responsible for the initiation of major neurodegenerative
      disorders of the eye leading to blindness, including age-related macular
      degeneration, Stargardt and Best diseases, are poorly understood. Accumulation of
      vitamin A dimers, such as N-retinylidene-N-retinylethanolamine (A2E) in the
      retinal pigment epithelium (RPE), is one of the earliest measurable events
      preceding retinal degeneration. However, the extent to which these dimers
      contribute to tissue degeneration is not clear. To determine if A2E could trigger
      morphological changes associated with the degenerating RPE and subsequent cell
      death, we evaluated its toxicity to cultured human RPE cells (ARPE-19). We show
      that A2E triggered the accumulation of debris followed by a protracted death. A2E
      was up to ~ 14-fold more toxic than its precursor, retinaldehyde. Measurements
      reveal that the concentration of A2E in the aged human eye could exceed the
      concentration of all other retinoids, opening the possibility of A2E-triggered
      cell death by several reported mechanisms. Findings suggest that accumulation of
      vitamin A dimers such as A2E in the human eye might be responsible for the
      formation of ubiquitous RPE debris, an early indication of retinal degeneration,
      and that preventing or reducing the accumulation of vitamin A dimers is a prudent
      strategy to prevent blindness.

PMID- 25058424
TI  - DJ-1 interactions with alpha-synuclein attenuate aggregation and cellular
      toxicity in models of Parkinson's disease.
AB  - Parkinson's disease (PD) is a devastating neurodegenerative disorder
      characterized by the loss of neurons in the substantia nigra pars compacta and
      the presence of Lewy bodies in surviving neurons. These intracellular protein
      inclusions are primarily composed of misfolded alpha-synuclein (aSyn), which has
      also been genetically linked to familial and sporadic forms of PD. DJ-1 is a
      small ubiquitously expressed protein implicated in several pathways associated
      with PD pathogenesis. Although mutations in the gene encoding DJ-1 lead to
      familial early-onset PD, the exact mechanisms responsible for its role in PD
      pathogenesis are still elusive. Previous work has found that DJ-1--which has
      protein chaperone-like activity--modulates aSyn aggregation. Here, we
      investigated possible physical interactions between aSyn and DJ-1 and any
      consequent functional and pathological relevance. We found that DJ-1 interacts
      directly with aSyn monomers and oligomers in vitro, and that this also occurs in
      living cells. Notably, several PD-causing mutations in DJ-1 constrain this
      interaction. In addition, we found that overexpression of DJ-1 reduces aSyn
      dimerization, whereas mutant forms of DJ-1 impair this process. Finally, we found
      that human DJ-1 as well as yeast orthologs of DJ-1 reversed aSyn-dependent
      cellular toxicity in Saccharomyces cerevisiae. Taken together, these data suggest
      that direct interactions between DJ-1 and aSyn constitute the basis for a
      neuroprotective mechanism and that familial mutations in DJ-1 may contribute to
      PD by disrupting these interactions.

PMID- 25058425
TI  - Immortalised breast epithelia survive prolonged DNA replication stress and return
      to cycle from a senescent-like state.
AB  - Mammalian cells have mechanisms to counteract the effects of metabolic and
      exogenous stresses, many of that would be mutagenic if ignored. Damage arising
      during DNA replication is a major source of mutagenesis. The extent of damage
      dictates whether cells undergo transient cell cycle arrest and damage repair,
      senescence or apoptosis. Existing dogma defines these alternative fates as
      distinct choices. Here we show that immortalised breast epithelial cells are able
      to survive prolonged S phase arrest and subsequently re-enter cycle after many
      days of being in an arrested, senescence-like state. Prolonged cell cycle
      inhibition in fibroblasts induced DNA damage response and cell death. However, in
      immortalised breast epithelia, efficient S phase arrest minimised chromosome
      damage and protected sufficient chromatin-bound replication licensing complexes
      to allow cell cycle re-entry. We propose that our observation could have
      implications for the design of drug therapies for breast cancer. 

PMID- 25058426
TI  - Defects of protein production in erythroid cells revealed in a zebrafish Diamond
      Blackfan anemia model for mutation in RPS19.
AB  - Diamond-Blackfan anemia (DBA) is a rare congenital red cell aplasia that
      classically presents during early infancy in DBA patients. Approximately, 25% of
      patients carry a mutation in the ribosomal protein (RP) S19 gene; mutations in
      RPS24, RPS17, RPL35A, RPL11, and RPL5 have been reported. How ribosome protein
      deficiency causes defects specifically to red blood cells in DBA has not been
      well elucidated. To genetically model the predominant ribosome defect in DBA, we
      generated an rps19 null mutant through the use of TALEN-mediated gene targeting
      in zebrafish. Molecular characterization of this mutant line demonstrated that
      rps19 deficiency reproduced the erythroid defects of DBA, including a lack of
      mature red blood cells and p53 activation. Notably, we found that rps19 mutants'
      production of globin proteins was significantly inhibited; however, globin
      transcript level was either increased or unaffected in rps19 mutant embryos. This
      dissociation of RNA/protein levels of globin genes was confirmed in another
      zebrafish DBA model with defects in rpl11. Using transgenic zebrafish with
      specific expression of mCherry in erythroid cells, we showed that protein
      production in erythroid cells was decreased when either rps19 or rpl11 was
      mutated. L-Leucine treatment alleviated the defects of protein production in
      erythroid cells and partially rescued the anemic phenotype in both rps19 and
      rpl11 mutants. Analysis of this model suggests that the decreased protein
      production in erythroid cells likely contributes to the blood-specific phenotype
      of DBA. Furthermore, the newly generated rps19 zebrafish mutant should serve as a
      useful animal model to study DBA. Our in vivo findings may provide clues for the
      future therapy strategy for DBA. 

PMID- 25058427
TI  - Facile synthesis of iridium nanocrystals with well-controlled facets using seed
      mediated growth.
AB  - Iridium nanoparticles have only been reported with roughly spherical shapes and
      sizes of 1-5 nm, making it impossible to investigate their facet-dependent
      catalytic properties. Here we report for the first time a simple method based on
      seed-mediated growth for the facile synthesis of Ir nanocrystals with well
      controlled facets. The essence of this approach is to coat an ultrathin conformal
      shell of Ir on a Pd seed with a well-defined shape at a relatively high
      temperature to ensure fast surface diffusion. In this way, the facets on the
      initial Pd seed are faithfully replicated in the resultant Pd@Ir core-shell
      nanocrystal. With 6 nm Pd cubes and octahedra encased by {100} and {111} facets,
      respectively, as the seeds, we have successfully generated Pd@Ir cubes and
      octahedra covered by Ir{100} and Ir{111} facets. The Pd@Ir cubes showed higher H2
      selectivity (31.8% vs 8.9%) toward the decomposition of hydrazine compared with
      Pd@Ir octahedra with roughly the same size. 

PMID- 25058428
TI  - Cytotoxic and vasogenic cerebral oedema in traumatic brain injury: assessment
      with FLAIR and DWI imaging.
AB  - PRIMARY OBJECTIVE: Cerebral oedema is a common complication of traumatic brain
      injury (TBI). The use of Fluid-Attenuated Inversion Recovery (FLAIR) imaging in
      combination with Diffusion Weighted Imaging (DWI) has the potential to
      distinguish between cytotoxic and vasogenic oedema. This study hypothesized a
      significant relationship between cytotoxic lesion volume and outcome. RESEARCH
      DESIGN: This observational study reports on a convenience sample where MRI was
      obtained for clinical purposes. METHODS AND PROCEDURES: Clinical post-TBI FLAIR
      and DWI images were analysed. For this study, lesions were defined as primarily
      cytotoxic oedema if the ratio of FLAIR to DWI lesion volume was comparable,
      defined as a ratio <2. If the ratio of FLAIR to DWI lesion volume was >=2, oedema
      was considered predominantly of vasogenic origin. MAIN OUTCOMES AND RESULTS: The
      sample consisted primarily of males with TBIs whose injury severity ranged from
      complicated mild to severe. Analysis revealed that both oedema types are common
      after TBI and both are associated with functional deficits 6 months after injury.
      CONCLUSIONS: Acute MRI may be useful to assess pathology at the tissue after
      traumatic brain injury. Clinical trials targeting cytotoxic and vasogenic
      mechanisms of oedema formation may benefit from using DWI and FLAIR MRI as a
      means to differentiate the predominant oedema type after TBI.

PMID- 25058430
TI  - Downregulation of inflammatory mediators and pro-inflammatory cytokines by
      alkaloids of Jeevaneeya rasayana in adjuvant-induced arthritis.
AB  - Jeevaneeya rasayana is an ayurvedic polyherbal formulation, with antirheumatic
      potential. The present study investigates the therapeutic efficacy of isolated
      total alkaloid fraction of Jeevaneeya Rasayana (AJR) in treating rheumatoid
      arthritis in a rat model of Adjuvant-induced arthritis (AIA). Paw swelling,
      inflammatory mediators such as cyclooxygenase-2 (COX-2), matrix metalloproteinase
      9 (MMP-9), level of prostaglandin E2 (PGE2), expression of cytokines and serum
      nitric oxide (NO) level were analyzed in experimental rats after an experimental
      period of 21 days. Arthritic induction significantly increased paw edema, and up
      regulated the inflammatory mediators and cytokines. Administration of AJR
      significantly reversed the paw edema, reduced the level of PGE2, serum NO and
      decreased the COX-2 activity in the paw tissue. AJR treatment also downregulated
      mRNA expression of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6) and MMP-9 in paw tissue. HPTLC analysis revealed the
      presence of 5 different alkaloid compounds in AJR. These findings suggest that
      the AJR have the therapeutic potential against adjuvant-induced arthritis.

PMID- 25058429
TI  - Lytic gene expression is frequent in HSV-1 latent infection and correlates with
      the engagement of a cell-intrinsic transcriptional response.
AB  - Herpes simplex viruses (HSV) are significant human pathogens that provide one of
      the best-described examples of viral latency and reactivation. HSV latency occurs
      in sensory neurons, being characterized by the absence of virus replication and
      only fragmentary evidence of protein production. In mouse models, HSV latency is
      especially stable but the detection of some lytic gene transcription and the
      ongoing presence of activated immune cells in latent ganglia have been used to
      suggest that this state is not entirely quiescent. Alternatively, these findings
      can be interpreted as signs of a low, but constant level of abortive reactivation
      punctuating otherwise silent latency. Using single cell analysis of transcription
      in mouse dorsal root ganglia, we reveal that HSV-1 latency is highly dynamic in
      the majority of neurons. Specifically, transcription from areas of the HSV genome
      associated with at least one viral lytic gene occurs in nearly two thirds of
      latently-infected neurons and more than half of these have RNA from more than one
      lytic gene locus. Further, bioinformatics analyses of host transcription showed
      that progressive appearance of these lytic transcripts correlated with
      alterations in expression of cellular genes. These data show for the first time
      that transcription consistent with lytic gene expression is a frequent event,
      taking place in the majority of HSV latently-infected neurons. Furthermore, this
      transcription is of biological significance in that it influences host gene
      expression. We suggest that the maintenance of HSV latency involves an active
      host response to frequent viral activity. 

PMID- 25058431
TI  - Sexually dimorphic distribution of calcium-binding protein, calretinin in the
      preoptic area of the freshwater catfish, Clarias batrachus (Linn.).
AB  - Preoptic area (POA) plays an important role in the hormonal regulation of the
      pituitary gland in vertebrates. In this study we report the sexually dimorphic
      distribution of calcium-binding proteins calretinin (CR) in the POA in the
      freshwater catfish, Clarias batrachus. Nissl staining highlighted the presence of
      the nucleus praeopticus periventricularis (NPP) and other subdivisions of the
      nucleus praeopticus (NPO), including supraoptic (NPOs), paraventricular (NPOp)
      and magnocellular (NPOm) divisions. In NPO, CR immunoreactivity was noted only in
      females but not in males. In both sexes, CR stained perikarya were found in the
      NPP. Sexually dimorphic localization of CR in the POA supports the notion that CR
      may play a gender-specific role and may be involved in hormonal regulation in
      fishes. 

PMID- 25058432
TI  - The neural connectivity of the intralaminar thalamic nuclei in the human brain: a
      diffusion tensor tractography study.
AB  - Research on the neural connectivity of the intralaminar thalamic nuclei (ILN) has
      been limited. Since the introduction of diffusion tensor imaging (DTI), many
      probabilistic DTI studies have reported on neural connectivity of neural
      structures in normal subjects. However, no study on the neural connectivity of
      the ILN has been reported so far. In this study, using probabilistic DTI, we
      investigated the neural connectivity of the ILN in normal subjects. A total of 40
      healthy subjects were recruited for this study. A seed region of interest was
      placed on the ILN of the thalamus using the FMRIB Software Library. Connectivity
      was defined as the incidence of connection between the ILN and target brain
      areas. We found high connectivity between the ILN and arousal-related areas
      (prefrontal cortex 100%, reticular formation 100%, pedunculopontine nucleus
      97.5%, basal forebrain 95%, and hypothalamus 92.5% at threshold 5), attention
      related area (prefrontal cortex 100% at threshold 5), and sensori-motor function
      related areas (primary motor cortex 100%, globus pallidus 100%, putamen 98.8%,
      premotor cortex 96.3%, primary somatosensory cortex 95.0%, caudate nucleus 92.5%,
      and posterior parietal cortex 90.0% at threshold 5). Findings of this study
      showed that ILN has high connectivity with brain areas related to arousal,
      attention, and sensorimotor function. This result indicates a close association
      of ILN with these functions in the human brain. 

PMID- 25058433
TI  - Sexual experience influences mating-induced activity in nitric oxide synthase
      containing neurons in the medial preoptic area.
AB  - Nitric oxide (NO) acts in the medial preoptic area (mPOA) of the hypothalamus to
      facilitate the expression of male sexual behavior and has also been widely
      implicated in mechanisms of experience, learning, and memory. Using
      immunohistochemistry for Fos, as a marker for neural activity, and nitric oxide
      synthase (NOS), the enzyme that catalyzes the production of nitric oxide (NO), we
      examined whether sexual activity and sexual experience influence Fos co
      expression in NOS-containing neurons in the mPOA of male rats. Consistent with
      previous findings, results indicate that mating increased activity in the mPOA,
      and that sexual experience facilitated the expression of sexual behaviors,
      together with increased mating-induced Fos and NOS in the mPOA. Results also
      indicate that mating increased co-expression of Fos in NOS-containing neurons,
      and that this increase was highest in animals undergoing their first sexual
      encounter, indicating that initial sexual experience increases NO production in
      the mPOA of male rats. 

PMID- 25058443
TI  - A novel mechanism regulating a sexual signal: the testosterone-based inhibition
      of female sex pheromone expression in garter snakes.
AB  - Vertebrates communicate their sex to conspecifics through the use of sexually
      dimorphic signals, such as ornaments, behaviors and scents. Furthermore, the
      physiological connection between hormones and secondary sexual signal expression
      is key to understanding their dimorphism, seasonality and evolution. The red
      sided garter snake (Thamnophis sirtalis parietalis) is the only reptile for which
      a described pheromone currently exists, and because garter snakes rely completely
      on the sexual attractiveness pheromone for species identification and mate
      choice, they constitute a unique model species for exploring the relationship
      between pheromones and the endocrine system. We recently demonstrated that
      estrogen can activate female pheromone production in male garter snakes. The
      purpose of this study was to determine the mechanism(s) acting to prevent female
      pheromone production in males. We found that castrated males (GX) are courted by
      wild males in the field and produce appreciable amounts of female sex pheromone.
      Furthermore, pheromone production is inhibited in castrates given testosterone
      implants (GX+T), suggesting that pheromone production is actively inhibited by
      the presence of testosterone. Lastly, testosterone supplementation alone (T)
      increased the production of several saturated methyl ketones in the pheromone but
      not the unsaturated ketones; this may indicate that saturated ketones are
      testosterone-activated components of the garter snake's skin lipid milieu.
      Collectively, our research has shown that pheromone expression in snakes results
      from two processes: activation by the feminizing steroid estradiol and inhibition
      by testosterone. We suggest that basal birds and garter snakes share common
      pathways of activation that modulate crucial intraspecific signals that originate
      from skin. 

PMID- 25058445
TI  - Atorvastatin restores arsenic-induced vascular dysfunction in rats: modulation of
      nitric oxide signaling and inflammatory mediators.
AB  - We evaluated whether atorvastatin, an extensively prescribed statin for reducing
      the risks of cardiovascular diseases, can reduce the risk of arsenic-induced
      vascular dysfunction and inflammation in rats and whether the modulation could be
      linked to improvement in vascular NO signaling. Rats were exposed to sodium
      arsenite (100ppm) through drinking water for 90 consecutive days. Atorvastatin
      (10mg/kg bw, orally) was administered once daily during the last 30days of
      arsenic exposure. On the 91(st) day, blood was collected for measuring serum C
      reactive protein. Thoracic aorta was isolated for assessing reactivity to
      phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS
      mRNA expression and measuring NO production, while abdominal aorta was used for
      ELISA of cytokines, chemokine and vascular cell adhesion molecules.
      Histopathology was done in aortic arches. Arsenic did not alter phenylephrine
      elicited contraction. Atorvastatin inhibited Emax of phenylephrine, but it
      augmented the contractile response in aortic rings from arsenic-exposed animals.
      Sodium nitroprusside-induced relaxation was not altered with any treatment.
      However, arsenic reduced acetylcholine-induced relaxation and affected aortic
      eNOS at the levels of mRNA expression, protein concentration, phosphorylation and
      NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO
      synthesis, production of pro-inflammatory mediators (IL-1beta, IL-6, MCP-1, VCAM,
      sICAM) and serum C-reactive protein and aortic vasculopathic lesions.
      Atorvastatin attenuated these arsenic-mediated functional, biochemical and
      structural alterations. Results show that atorvastatin has the potential to
      ameliorate arsenic-induced vascular dysfunction and inflammation by restoring
      endothelial function with improvement in NO signaling and attenuating production
      of pro-inflammatory mediators and cell adhesion molecules. 

PMID- 25058444
TI  - Porphyromonas gingivalis GroEL induces osteoclastogenesis of periodontal ligament
      cells and enhances alveolar bone resorption in rats.
AB  - Porphyromonas gingivalis is a major periodontal pathogen that contains a variety
      of virulence factors. The antibody titer to P. gingivalis GroEL, a homologue of
      HSP60, is significantly higher in periodontitis patients than in healthy control
      subjects, suggesting that P. gingivalis GroEL is a potential stimulator of
      periodontal disease. However, the specific role of GroEL in periodontal disease
      remains unclear. Here, we investigated the effect of P. gingivalis GroEL on human
      periodontal ligament (PDL) cells in vitro, as well as its effect on alveolar bone
      resorption in rats in vivo. First, we found that stimulation of PDL cells with
      recombinant GroEL increased the secretion of the bone resorption-associated
      cytokines interleukin (IL)-6 and IL-8, potentially via NF-kappaB activation.
      Furthermore, GroEL could effectively stimulate PDL cell migration, possibly
      through activation of integrin alpha1 and alpha2 mRNA expression as well as
      cytoskeletal reorganization. Additionally, GroEL may be involved in
      osteoclastogenesis via receptor activator of nuclear factor kappa-B ligand
      (RANKL) activation and alkaline phosphatase (ALP) mRNA inhibition in PDL cells.
      Finally, we inoculated GroEL into rat gingiva, and the results of microcomputed
      tomography (micro-CT) and histomorphometric assays indicated that the
      administration of GroEL significantly increased inflammation and bone loss. In
      conclusion, P. gingivalis GroEL may act as a potent virulence factor,
      contributing to osteoclastogenesis of PDL cells and resulting in periodontal
      disease with alveolar bone resorption. 

PMID- 25058447
TI  - Oro-dental mucoadhesive proniosomal gel formulation loaded with lornoxicam for
      management of dental pain.
AB  - Oro-dental diseases are generally associated with pain that is controlled using
      oral tablets containing NSAIDs. Lornoxicam, a relatively new NSAID, is effective
      in relieving pain accompanying different oro-dental problems. The aim of the
      current research is to prepare oro-dental analgesic and anti-inflammatory gel
      using provesicular approach to deliver lornoxicam directly to the site of action
      in the oral cavity. Local administration of lornoxicam is expected to be superior
      to systemic delivery in pain relieving and poses less GIT adverse effects.
      Different surfactants were utilized to prepare the proniosomal gels that rapidly
      transform into nano-sized niosomes after hydration with the oral saliva. The
      effect of the surfactant structure on vesicles size distribution and entrapment
      efficiency percentage (EE%) was investigated. The proniosomal formulations were
      incorporated into carbopol hydrogels that were characterized regarding
      rheological and mucoadhesion properties. Moreover, ex-vivo mucosal membrane
      permeation studies were conducted for selected proniosomal gels to quantify the
      permeation parameters and assess the amount of drug deposited within the oral
      mucosa. Results revealed that mucoadhesive proniosomes formulation prepared using
      Span 60 was optimal as it was nano-sized and also showed the highest EE%. The
      transmucosal flux of lornoxicam, from these proniosomal formulations, across the
      oral mucosa was significantly higher (p < 0.05) than lornoxicam containing
      carbopol gel and the percent drug diffused increased more than twofolds. The
      results collectively suggest that the mucoadhesive proniosomal gels can be
      assertively considered as a promising carrier for transmucosal delivery of
      lornoxicam into the oral cavity. 

PMID- 25058446
TI  - Prediction of binding affinity and efficacy of thyroid hormone receptor ligands
      using QSAR and structure-based modeling methods.
AB  - The thyroid hormone receptor (THR) is an important member of the nuclear receptor
      family that can be activated by endocrine disrupting chemicals (EDC).
      Quantitative Structure-Activity Relationship (QSAR) models have been developed to
      facilitate the prioritization of THR-mediated EDC for the experimental
      validation. The largest database of binding affinities available at the time of
      the study for ligand binding domain (LBD) of THRbeta was assembled to generate
      both continuous and classification QSAR models with an external accuracy of
      R(2)=0.55 and CCR=0.76, respectively. In addition, for the first time a QSAR
      model was developed to predict binding affinities of antagonists inhibiting the
      interaction of coactivators with the AF-2 domain of THRbeta (R(2)=0.70).
      Furthermore, molecular docking studies were performed for a set of THRbeta
      ligands (57 agonists and 15 antagonists of LBD, 210 antagonists of the AF-2
      domain, supplemented by putative decoys/non-binders) using several THRbeta
      structures retrieved from the Protein Data Bank. We found that two agonist-bound
      THRbeta conformations could effectively discriminate their corresponding ligands
      from presumed non-binders. Moreover, one of the agonist conformations could
      discriminate agonists from antagonists. Finally, we have conducted virtual
      screening of a chemical library compiled by the EPA as part of the Tox21 program
      to identify potential THRbeta-mediated EDCs using both QSAR models and docking.
      We concluded that the library is unlikely to have any EDC that would bind to the
      THRbeta. Models developed in this study can be employed either to identify
      environmental chemicals interacting with the THR or, conversely, to eliminate the
      THR-mediated mechanism of action for chemicals of concern. 

PMID- 25058448
TI  - Mechanistic study on the photochemical "light switch" behavior of
      [Ru(bpy)2dmdppz]2+.
AB  - [Ru(bpy)2dmdppz](2+) (bpy = 2,2'-bipyridine and dmdppz = 3,6-dimethyl
      dipyridylphenazine), a strained Ru(II) polypyridyl complex, is a derivative of
      the well-known luminescent "light switch", [Ru(bpy)2dppz](2+) (dppz =
      dipyridylphenazine). [Ru(bpy)2dmdppz](2+) is of interest because it acts as a
      photochemical sensor and metalating agent for DNA. Here we report a detailed
      study to elucidate the mechanism of ligand substitution by investigating the
      photochemical reaction in a variety of solvents and by determining the effects of
      different incoming ligands, the incoming ligand concentration, and the
      temperature dependence. Results from these studies indicate that the mechanism of
      substitution is associative or interchange associative, in contrast with the
      dissociative mechanism of other photolabile Ru(II) polypyridyl complexes. 

PMID- 25058449
TI  - Fibrillogenesis from nanosurfaces: multiphoton imaging and stereological analysis
      of collagen 3D self-assembly dynamics.
AB  - The assembly of proteins into fibrillar structures is an important process that
      concerns different biological contexts, including molecular medicine and
      functional biomaterials. Engineering of hybrid biomaterials can advantageously
      provide synergetic interactions of the biopolymers with an inorganic component to
      ensure specific supramolecular organization and dynamics. To this aim, we
      designed hybrid systems associating collagen and surface-functionalized silica
      particles and we built a new strategy to investigate fibrillogenesis processes in
      such multicomponents systems, working at the crossroads of chemistry, physics and
      mathematics. The self-assembly process was investigated by bimodal multiphoton
      imaging coupling second harmonic generation (SHG) and 2 photon excited
      fluorescence (2PEF). The in-depth spatial characterization of the system was
      further achieved using the three-dimensional analysis of the SHG/2PEF data via
      mathematical morphology processing. Quantitation of collagen distribution around
      particles offers strong evidence that the chemically induced confinement of the
      protein on the silica nanosurfaces has a key influence on the spatial extension
      of fibrillogenesis. This new approach is unique in the information it can provide
      on 3D dynamic hybrid systems and may be extended to other associations of
      fibrillar molecules with optically responsive nano-objects. 

PMID- 25058450
TI  - Application of a portable near infrared spectrometer for presumptive
      identification of psychoactive drugs.
AB  - A portable near infrared spectrometer was applied to the presumptive
      identification of psychotropic drugs based on library searching. Data-treatment
      methods (mathematical pretreatment and library search algorithm) were examined on
      the basis of differentiation ability. The optimized mathematical pretreatment was
      a standard normal variate followed by the 2nd derivative. The correlation
      coefficient showed the best differentiation ability in the library search
      algorithms. Optimized data-treatment was effective for minimizing the effect of
      particle size on identification. The optimized data-treatment methods were
      validated by the spectra of psychotropic substances (n=120). Identification
      criteria for the psychotropic drugs were decided on the basis of the results of
      the validation. As a consequence, 8 out of 11 forensic samples containing
      psychoactive substances were able to be positively identified. Thus, the portable
      near infrared spectrometer with optimized data-treatment processing is a useful
      tool for rapid screening and presumptive identification of seized materials. 

PMID- 25058451
TI  - Accuracy of standard craniometric measurements using multiple data formats.
AB  - With continuing advancements in biomedical imaging technologies, anthropologists
      are increasingly making use of data derived from indirect measurement and
      analysis of skeletal material. To that end, the purpose of this study was to test
      the reliability of 26 standard craniometric measurements routinely utilized in
      forensic casework across several different imaging technologies. Measurements
      from five crania of known individuals were collected in duplicate by two
      anthropologists via computed tomography (CT) scans and three-dimensional (3D)
      laser scans of the known skulls. The laser scans were also used to create
      prototype models of the known skulls. These prototypes were, themselves, laser
      scanned, and measurements were also collected from the prototypes and the laser
      scans of the prototypes. Measurement sets from each technology were then compared
      with one another using the previously collected osteometric measurements taken on
      the crania themselves as the ground truth. RESULT: indicate that, while the
      majority of measurements showed no significant differences across data formats, a
      handful were found to be problematic for particular technologies. For instance,
      measurements taken in a supero-inferior direction (e.g., BBH, OBH) from CT scans
      were prone to greater deviation from direct measurements of the cranium than
      other technologies, especially for CT scans taken at 5 mm thickness and
      increment. Also, several measurements defined by Type 1 landmarks, particularly
      those occurring at complicated or indistinct suture junctures (e.g., ASB, ZMB),
      were found to have high variance across all technologies while measurements based
      on Type 3 landmarks proved to be highly reproducible. This is contrary to
      measurements taken directly on crania, in which measures defined by Type 1
      landmarks are typically the most reliable, likely attributable to diminished or
      totally obscured suture definition in the scan data. If medical imaging data are
      to be increasingly utilized in anthropological studies, it may be prudent to bear
      in mind that the reliability of measurements taken on an actual skull may not be
      the same as for measurements taken from medical scans.

PMID- 25058452
TI  - Arrayed lipid bilayer chambers allow single-molecule analysis of membrane
      transporter activity.
AB  - Nano- to micron-size reaction chamber arrays (femtolitre chamber arrays) have
      facilitated the development of sensitive and quantitative biological assays, such
      as single-molecule enzymatic assays, digital PCR and digital ELISA. However, the
      versatility of femtolitre chamber arrays is limited to reactions that occur in
      aqueous solutions. Here we report an arrayed lipid bilayer chamber system (ALBiC)
      that contains sub-million femtolitre chambers, each sealed with a stable 4-MUm
      diameter lipid bilayer membrane. When reconstituted with a limiting amount of the
      membrane transporter proteins alpha-hemolysin or F0F1-ATP synthase, the chambers
      within the ALBiC exhibit stochastic and quantized transporting activities. This
      demonstrates that the single-molecule analysis of passive and active membrane
      transport is achievable with the ALBiC system. This new platform broadens the
      versatility of femtolitre chamber arrays and paves the way for novel applications
      aimed at furthering our mechanistic understanding of membrane proteins' function.

PMID- 25058453
TI  - Altered expression of p21, activated caspase-3, and PCNA in bronchiolar
      epithelium of smokers with and without chronic obstructive pulmonary disease.
AB  - ABSTRACT Background: The cyclin-dependent kinase inhibitor p21CIP1/WAF1 is
      involved in cell-cycle growth arrest due to cell stressors, such as cigarette
      smoke. The role of p21 in cell apoptosis is controversial as it exerts pro- or
      antiapoptotic effects in different cells. In the present study, we investigated
      whether, in the epithelium of small airways of smokers with and without COPD,
      altered p21 expression is associated with an imbalance between proliferation and
      apoptosis. OBJECTIVES AND METHODS: The expression of specific molecules involved
      in the regulation of apoptosis, such as activated caspase-3 and cytoplasmic p21,
      cell quiescence (G0) or proliferation markers such as Ki67 and PCNA, and cell
      cycle markers such as the nuclear p21, was assessed in the small airway
      (bronchiolar) epithelium of smokers with and without COPD and in nonsmoker non
      COPD subjects. RESULTS: In smokers with and without COPD, we found an increase of
      cytoplasmic nuclear p21 and activated caspase-3 expression. By contrast, we
      verified in all the studied groups a similar low expression of the proliferation
      marker Ki67 and a reduced expression of PCNA in smokers and smokers with COPD.
      CONCLUSIONS: In the small airway epithelium, cytoplasmic p21 correlating with
      increased activated caspase-3 expression might play a proapoptotic role.
      Furthermore, p21 alteration may be associated with the inhibition of tissue
      repair in smokers and smokers with COPD as confirmed by the low expression of
      proliferation markers such as PCNA. All these events may play a role in the
      permanent cellular damage leading to the destruction of bronchiolar tissue.

PMID- 25058454
TI  - Selection and validation of reference genes for transcript normalization in gene
      expression studies in Catharanthus roseus.
AB  - Quantitative Real-Time PCR (qPCR), a sensitive and commonly used technique for
      gene expression analysis, requires stably expressed reference genes for
      normalization of gene expression. Up to now, only one reference gene for qPCR
      analysis, corresponding to 40S Ribosomal protein S9 (RPS9), was available for the
      medicinal plant Catharanthus roseus, the only source of the commercial anticancer
      drugs vinblastine and vincristine. Here, we screened for additional reference
      genes for this plant species by mining C. roseus RNA-Seq data for orthologs of 22
      genes known to be stably expressed in Arabidopsis thaliana and qualified as
      superior reference genes for this model plant species. Based on this, eight
      candidate C. roseus reference genes were identified and, together with RPS9,
      evaluated by performing qPCR on a series of different C. roseus explants and
      tissue cultures. NormFinder, geNorm and BestKeeper analyses of the resulting qPCR
      data revealed that the orthologs of At2g28390 (SAND family protein, SAND),
      At2g32170 (N2227-like family protein, N2227) and At4g26410 (Expressed protein,
      EXP) had the highest expression stability across the different C. roseus samples
      and are superior as reference genes as compared to the traditionally used RPS9.
      Analysis of publicly available C. roseus RNA-Seq data confirmed the expression
      stability of SAND and N2227, underscoring their value as reference genes for C.
      roseus qPCR analysis. 

PMID- 25058455
TI  - Alternative methods for the use of non-human primates in biomedical research.
AB  - The experimental use of non-human primates (NHP) in Europe is tightly regulated
      and is only permitted when there are no alternatives available. As a result, NHP
      are most often used in late, pre-clinical phases of biomedical research. Although
      the impetus for scientists, politicians and the general public to replace, reduce
      and refine NHP in biomedical research is strong, the development of 3Rs
      technology for NHP poses specific challenges. In February 2014 a workshop on
      "Alternative methods for the use of NHP in biomedical research" was organized
      within the international exchange program of EUPRIM-Net II, a European
      infrastructure initiative that links biomedical primate research centers. The
      workshop included lectures by key scientists in the field of alternatives as well
      as by experts from governmental and non-governmental organizations. Furthermore,
      parallel sessions were organized to stimulate discussion on the challenges of
      advancing the use of alternative methods for NHP. Subgroups voted on four
      statements and together composed a list with opportunities and priorities. This
      report summarizes the presentations that were held, the content of the discussion
      sessions and concludes with recommendations on 3Rs development for NHP
      specifically. These include technical, conceptual as well as political topics.

PMID- 25058456
TI  - Patterns of Uveitis in a University-based Tertiary Referral Center in Riyadh,
      Saudi Arabia.
AB  - PURPOSE: To investigate the referral patterns and diagnosis of uveitis in a
      university-based tertiary referral center in Riyadh, Saudi Arabia. METHODS: We
      retrospectively reviewed the medical records of 642 patients (1220 eyes).
      RESULTS: There were 295 (46%) males and 347 (54%) female patients, with a mean
      age of 36.4 +/- 16.1 years at presentation. Panuveitis was most common (47.1%),
      followed by anterior uveitis (36.8%), posterior uveitis (10.7%), and intermediate
      uveitis (5.4%). Nongranulomatous (85.2%) and noninfectious (69.3%) were the most
      frequent types of uveitis. The most identifiable specific diagnoses were Vogt
      Koyanagi-Harada (VKH) disease (19.6%), presumed tuberculous uveitis (PTU)
      (17.8%), Behcet disease (BD) (8.4%), and toxoplasmosis (6.9%). After a mean
      follow-up period of 31.3 +/- 31.5 months, 73.5% of the eyes achieved visual
      acuity of 20/40 or better. CONCLUSIONS: The most common anatomic diagnosis was
      panuveitis. VKH disease, PTU, BD, and toxoplasmosis are the most frequently
      diagnosed entities.

PMID- 25058457
TI  - Non-destructive observation of intact bacteria and viruses in water by the highly
      sensitive frequency transmission electric-field method based on SEM.
AB  - The high-resolution structural analysis of biological specimens by scanning
      electron microscopy (SEM) presents several advantages. Until now, wet bacterial
      specimens have been examined using atmospheric sample holders. However, images of
      unstained specimens in water using these holders exhibit very poor contrast and
      heavy radiation damage. Recently, we developed the frequency transmission
      electric-field (FTE) method, which facilitates the SEM observation of biological
      specimens in water without radiation damage. However, the signal detection system
      presents low sensitivity. Therefore, a high EB current is required to generate
      clear images, and thus reducing spatial resolution and inducing thermal damage to
      the samples. Here a high-sensitivity detection system is developed for the FTE
      method, which enhances the output signal amplitude by hundredfold. The detection
      signal was highly enhanced when voltage was applied to the metal layer on silicon
      nitride thin film. This enhancement reduced the EB current and improved the
      spatial resolution as well as the signal-to-noise ratio. The spatial resolution
      of a high-sensitive FTE system is 41nm, which is considerably higher than
      previous FTE system. New FTE system can easily be utilised to examine various
      unstained biological specimens in water, such as living bacteria and viruses.

PMID- 25058458
TI  - Arabidopsis CIPK14 positively regulates glucose response.
AB  - Calcium is a ubiquitous intracellular secondary messenger in plants. Calcineurin
      B-like proteins (CBLs), which contain four Ca(2+)-binding EF hand motifs, are
      Ca(2+) sensors and regulate a group of Ser/Thr protein kinases called CBL
      interacting protein kinases (CIPKs). Although the CBL-CIPK network has been
      demonstrated to play crucial roles in plant development and responses to various
      environmental stresses in Arabidopsis, little is known about their function in
      glucose signaling. In the present study, we identified CIPK14 gene from
      Arabidopsis that play a role in glucose signaling. The subcellular localization
      of CIPK14 was determined using green fluorescence protein (GFP) as the reporter.
      Furthermore, the expression levels of CIPK14 in response to salt, drought, cold,
      heat, ABA, methyl viologen (MV) and glucose treatments were examined by
      quantitative RT-PCR and it was found to respond to multiple stimuli, suggesting
      that CIPK14 may be a point of convergence for several different signaling
      pathways. Moreover, knock-out mutation of CIPK14 rendered it more sensitive to
      glucose treatment. Yeast two-hybrid assay demonstrated that CIPK14 interacted
      with three CBLs and also with two key kinases, sucrose non-fermenting 1-related
      kinase (SnRK) 1.1 and SnRK1.2 implicated in glucose signaling. This is the first
      report to demonstrate that CIPK also plays a role in glucose signaling. 

PMID- 25058459
TI  - Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased
      in triple negative breast cancer and correlates independently with clinical
      outcome.
AB  - BACKGROUND: (18)Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is
      being used for staging in many tumors however its impact on prognosis has never
      been studied in breast cancer. METHODS: Glycolytic and hypoxic markers: glucose
      transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1
      and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH
      A) were assessed by immunohistochemistry in two cohorts of breast cancer
      comprising 643 node-negative and 127 triple negative breast cancers (TNBC)
      respectively. RESULTS: In the 643 node-negative breast tumor cohort with a median
      follow-up of 124 months, TNBC were the most glycolytic (~70%), followed by Her-2
      (~50%) and RH-positive cancers (~30%). Tumoral MCT4 staining (without stromal
      staining) was a strong independent prognostic factor for metastasis-free survival
      (HR=0.47, P=0.02) and overall-survival (HR=0.38, P=0.002). These results were
      confirmed in the independent cohort of 127 cancer patients. CONCLUSION:
      Glycolytic markers are expressed in all breast tumors with highest expression
      occurring in TNBC. MCT4, the hypoxia-inducible lactate/H(+) symporter
      demonstrated the strongest deleterious impact on survival. We propose that MCT4
      serves as a new prognostic factor in node-negative breast cancer and can perhaps
      act soon as a theranostic factor considering the current pharmacological
      development of MCT4 inhibitors.

PMID- 25058460
TI  - Cytohesin-associated scaffolding protein (CASP) is involved in migration and IFN
      gamma secretion in natural killer cells.
AB  - Natural Killer (NK) cells are highly mobile, specialized sub-populations of
      lymphocytic cells that survey their host to identify and eliminate infected or
      tumor cells. They are one of the key players in innate immunity and do not need
      prior activation through antigen recognition to deliver cytotoxic packages and
      release messenger chemicals to recruit immune cells. Cytohesin associated
      scaffolding protein (CASP) is a highly expressed lymphocyte adaptor protein that
      forms complexes with vesicles and sorting proteins including SNX27 and Cytohesin
      1. In this study we show that by using stably integrated shRNA, CASP has a direct
      role in the secretion of IFN-gamma, and NK cell motility and ability to kill
      tumor cells. CASP polarizes to the leading edge of migrating NK cells, and to the
      immunological synapse when engaged with tumor cells. However, CASP is not
      associated with cytotoxic granule mediated killing. CASP is a multi-faceted
      protein, which has a very diverse role in NK cell specific immune functions. 

PMID- 25058461
TI  - Interaction of PKCalpha with the armadillo repeats facilitates the N-terminal
      phosphorylation of beta-catenin.
AB  - Protein kinase Calpha (PKCalpha) phosphorylates the Ser33/37/Thr41 residues of
      beta-catenin, which lacks a typical PKCalpha canonical sequence, but little is
      known about its underlying mechanism. Here we showed that Ser33/Ser37/Thr41 of
      beta-catenin fragments encompassing the armadillo repeats 1-5 (beta-catenin1-781,
      beta-catenin1-682, and beta-catenin1-422) are phosphorylated by PKCalpha whereas
      beta-catenin1-138 lacking these repeats is not phosphorylated. Binding-site
      analysis revealed that PKCalpha directly interacts with beta-catenin through the
      sites on the armadillo repeats 1-5. In addition, axin fragments (365-500), which
      interacts with beta-catenin through armadillo repeats 3-5, disrupted
      PKCalpha/beta-catenin association and inhibited beta-catenin phosphorylation by
      PKCalpha. In HEK293 cells, the levels of beta-catenin1-781 and beta-catenin1-422
      were decreased whereas the amount of beta-catenin1-138 was unchanged by
      pharmacological stimulation of PKCalpha. Our results suggest that the association
      of PKCalpha with the armadillo repeats of beta-catenin placed the Ser33/37/Thr41
      residues of beta-catenin in close proximity to PKCalpha, thereby facilitating
      PKCalpha-mediated beta-catenin phosphorylation.

PMID- 25058462
TI  - MiR-181a-5p is downregulated in hepatocellular carcinoma and suppresses motility,
      invasion and branching-morphogenesis by directly targeting c-Met.
AB  - c-Met receptor tyrosine kinase has been regarded as a promising therapeutic
      target for hepatocellular carcinoma (HCC). Recently, microRNAs (miRNAs) have been
      shown as a novel mechanism to control c-Met expression in cancer. In this study,
      we investigate the potential contribution of miR-181a-5p dysregulation to the
      biology of c-Met overexpression in HCC. Herein, we found an inverse expression
      pattern between miR-181a-5p and c-Met expression in normal, cirrhotic and HCC
      liver tissues. Luciferase assay confirmed that miR-181a-5p binding to the 3'-UTR
      of c-Met downregulated the expression of c-Met in HCC cells. Overexpression of
      miR-181a-5p suppressed both HGF-independent and -dependent activation of c-Met
      and consequently diminished branching-morphogenesis and invasion. Combined
      treatment with miR-181a-5p and c-Met inhibitor led to a further inhibition of c
      Met-driven cellular activities. Knockdown of miR-181a-5p promoted HGF
      independent/-dependent signaling of c-Met and accelerated migration, invasion and
      branching-morphogenesis. In conclusion, our results demonstrated for the first
      time that c-Met is a functional target gene of miR-181a-5p and the loss of miR
      181a-5p expression led to the activation of c-Met-mediated oncogenic signaling in
      hepatocarcinogenesis. These findings display a novel molecular mechanism of c-Met
      regulation in HCC and strategies to increase miR-181a5p level might be an
      alternative approach for the enhancement of the inhibitory effects of c-Met
      inhibitors. 

PMID- 25058463
TI  - Ovarian haemangioma with hyperandrogenism: a case report.

PMID- 25058464
TI  - Green tea polyphenols extend the lifespan of male drosophila melanogaster while
      impairing reproductive fitness.
AB  - Green tea is a popular beverage believed to have many health benefits, including
      a reduction in the risks of heart disease and cancer. Rich in polyphenolic
      compounds known as catechins, green tea and its components have been shown to
      increase the lifespan of various animal models, including Drosophila
      melanogaster. Here, we investigated the gender-specific effects of green tea on
      the lifespan of fruit flies and observed that green tea extended the lifespan of
      male flies only. This effect was found to be independent of typical aging
      interventions, such as dietary restriction, modulation of oxidative energy
      metabolism, and improved tolerance to environmental stresses. The one exception
      was that green tea did protect male flies against iron toxicity. Since there is
      an inverse correlation between lifespan and reproduction, the impact of green tea
      on male reproductive fitness was also investigated. We found that green tea
      negatively impacted male fertility as shown by a reduced number of offspring
      produced and increased mating latency. We further identified that the lifespan
      extension properties of green tea was only observed in the presence of females
      which alludes to a reproductive (or mating) dependent mechanism. Our findings
      suggest that green tea extends the lifespan of male flies by inhibiting
      reproductive potential, possibly by limiting iron uptake. To our knowledge, our
      study is the first to report the negative impact of green tea on Drosophila male
      reproduction. Our results also support previous studies that suggest that green
      tea might have a negative effect on reproductive fitness in humans.

PMID- 25058465
TI  - Serological, molecular and entomological surveillance demonstrates widespread
      circulation of West Nile virus in Turkey.
AB  - West Nile virus (WNV), a mosquito-borne flavivirus with significant impact on
      human and animal health, has recently demonstrated an expanded zone of activity
      globally. The aim of this study is to investigate the frequency and distribution
      of WNV infections in potential vectors and several mammal and avian species in
      Turkey, where previous data indicate viral circulation. The study was conducted
      in 15 provinces across Turkey during 2011-2013. In addition, the entomological
      study was extended to 4 districts of the Turkish Republic of Northern Cyprus. WNV
      exposure was determined in humans, horses, sheep and ducks from Mersin,
      Sanliurfa, Van and Kars provinces of Turkey, via the detection of neutralizing
      antibodies. WNV RNA was sought in human and equine samples from Mersin, Adana and
      Mugla provinces. Field-collected mosquitoes from 92 sites at 46 locations were
      characterized morphologically and evaluated for viral RNA. Neutralizing
      antibodies were identified in 10.5% of the 1180 samples studied and detected in
      all species evaluated. Viral nucleic acids were observed in 5.9% of 522 samples
      but only in horses. A total of 2642 mosquito specimens belonging to 15 species
      were captured, where Ochlerotatus caspius (52.4%), Culex pipiens sensu lato
      (24.2%) comprise the most frequent species. WNV RNA was detected in 4 mosquito
      pools (1.9%), that comprise Oc. caspius Cx. pipiens s.l. and DNA barcoding
      revealed the presence of Cx. quinquefasciatus and Cx. perexiguus mosquitoes in
      infected Culex pools. All WNV partial sequences were characterized as lineage 1
      clade 1a. These findings indicate a widespread WNV activity in Turkey, in Eastern
      Thrace and Mediterranean-Aegean regions as well as Southeastern and Northeastern
      Anatolia. 

PMID- 25058466
TI  - Changes in the triterpenoid content of cuticular waxes during fruit ripening of
      eight grape (Vitis vinifera) cultivars grown in the Upper Rhine Valley.
AB  - Triterpenoids present in grape cuticular waxes are of interest due to their
      potential role in protection against biotic stresses, their impact on the
      mechanical toughness of the fruit surface, and the potential industrial
      application of these biologically active compounds from grape pomace. The
      determination of the triterpenoid profile of cuticular waxes reported here
      supplements existing knowledge of the chemical diversity of grape, with some
      compounds reported in this species for the first time. Common compounds
      identified in eight examined cultivars grown in the Upper Rhine Valley include
      oleanolic acid, oleanolic and ursolic acid methyl esters, oleanolic aldehyde,
      alpha-amyrin, alpha-amyrenone, beta-amyrin, cycloartanol, 24
      methylenecycloartanol, erythrodiol, germanicol, lupeol accompanied by lupeol
      acetate, campesterol, cholesterol, sitosterol, stigmasterol, and stigmasta-3,5
      dien-7-one, whereas 3,12-oleandione was specific for the Muscat d'Alsace
      cultivar. Changes in the triterpenoid content of cuticular waxes were determined
      at three different phenological stages: young grapes, grapes at veraison (the
      onset of ripening), and mature grapes. The results reveal a characteristic
      evolution of triterpenoid content during fruit development, with a high level of
      total triterpenoids in young grapes that gradually decreases with a slight
      increase in the level of neutral triterpenoids. This phenomenon may partially
      explain changes in the mechanical properties of the cuticle and possible
      modulations in the susceptibility to pathogens of mature grapes. 

PMID- 25058467
TI  - In vitro evaluation of intestinal epithelial TLR activation in preventing food
      allergic responses.
AB  - Alterations in the gut microbiota composition are associated with food allergy.
      Toll-like receptors (TLRs) respond to microbial stimuli. We studied the effects
      of the ligation of TLRs on intestinal epithelial cells (IECs) in preventing an
      allergic effector response. IEC monolayers (T84 cells) were co-cultured with
      CD3/28-activated PBMCs from healthy controls or atopic patients and
      simultaneously apically exposed to TLR2, TLR4 or TLR9 ligands. The barrier
      integrity of T84 cell monolayers was significantly reduced upon co-culture with
      PBMCs of food allergic subjects compared to healthy subjects. Apical exposure of
      IECs to a TLR9 ligand prevented PBMC-induced epithelial barrier disruption. Using
      PBMCs from food allergic subjects, apical TLR9 activation on IECs increased the
      IFN-gamma/IL-13 and IL-10/IL-13 ratio, while suppressing pro-inflammatory IL-6,
      IL-8 and TNF-alpha production in an IEC-dependent manner. Hence, the activation
      of apical TLR9 on IECs, potentially by microbiota-derived signals, may play an
      important role in the prevention of allergic inflammation. 

PMID- 25058468
TI  - Regulatory factor X transcription factors control Musashi1 transcription in mouse
      neural stem/progenitor cells.
AB  - The transcriptional regulation of neural stem/progenitor cells (NS/PCs) is of
      great interest in neural development and stem cell biology. The RNA-binding
      protein Musashi1 (Msi1), which is often employed as a marker for NS/PCs,
      regulates Notch signaling to maintain NS/PCs in undifferentiated states by the
      translational repression of Numb expression. Considering these critical roles of
      Msi1 in the maintenance of NS/PCs, it is extremely important to elucidate the
      regulatory mechanisms by which Msi1 is selectively expressed in these cells.
      However, the mechanism regulating Msi1 transcription is unclear. We previously
      reported that the transcriptional regulatory region of Msi1 is located in the
      sixth intron of the Msi1 locus in NS/PCs, based on in vitro experiments. In the
      present study, we generated reporter transgenic mice for the sixth intronic Msi1
      enhancer (Msi1-6IE), which show the reporter expression corresponding with
      endogenous Msi1-positive cells in developing and adult NS/PCs. We found that the
      core element responsible for this reporter gene activity includes palindromic
      Regulatory factor X (Rfx) binding sites and that Msi1-6IE was activated by Rfx.
      Rfx4, which was highly expressed in NS/PCs positive for the Msi1-6IE reporter,
      bound to this region, and both of the palindromic Rfx binding sites were required
      for the transactivation of Msi1-6IE. Furthermore, ectopic Rfx4 expression in the
      developing mouse cerebral cortex transactivates Msi1 expression in the
      intermediate zone. This study suggests that ciliogenic Rfx transcription factors
      regulate Msi1 expression through Msi1-6IE in NS/PCs. 

PMID- 25058469
TI  - Ambulatory-treated Clostridium difficile infection: a comparison of community
      acquired vs. nosocomial infection.
AB  - The purpose of this study was to identify the clinical outcomes of ambulatory
      treated Clostridium difficile infection (CDI) and risk factors associated with
      community-associated CDI (CA-CDI). Adult patients diagnosed with CDI in the
      institutional or ambulatory-care setting between 1 April 2005 and 30 April 2011,
      with no other CDI diagnosis in the previous 180 days, and who purchased an
      ambulatory, anti-CDI agent within 7 days of CDI diagnosis were included. A total
      of 1201 patients were included with 914 (76%) and 287 (24%) identified with CA
      CDI and nosocomial CDI (N-CDI), respectively. Patients with N-CDI were more
      likely to have had a recurrent CDI (P = 0.043) and died from any cause (P <
      0.001). Patients with CA-CDI were younger, healthier, and had fewer traditional
      risk factors compared to patients with N-CDI. To prevent CA-CDI, clinicians
      should be aware that patients at risk for CA-CDI are unique from those at risk
      for N-CDI.

PMID- 25058471
TI  - The new phase [Tl4Sb6Se10][Sn5Sb2Se14]: a naturally formed semiconducting
      heterostructure with two-dimensional conductance.
AB  - We report on a new layered semiconductor Tl8Sn10Sb16Se48 with an indirect band
      gap of 0.45 eV. The novel structure is made of alternating layers of SnSe2-type
      [Sn5Sb2Se14] and SnSe-type [Tl4Sb6Se10]. The material exhibits two-dimensional
      (2D) electron variable range hopping at low temperatures, indicating an absence
      of interlayer coherency of the electronic state. Theoretical calculations unveil
      a 2D confinement for electrons in the [Sn5Sb2Se14] sheet and confirm the
      heterostructure nature. This unique electronic structure is attributed to the
      weak interlayer coupling and structure distortion in the electron-poor
      [Tl4Sb6Se10] layer that energetically impedes electron propagation. 

PMID- 25058470
TI  - How many antimicrobial peptide molecules kill a bacterium? The case of PMAP-23.
AB  - Antimicrobial peptides (AMPs) kill bacteria mainly through the perturbation of
      their membranes and are promising compounds to fight drug resistance. Models of
      the mechanism of AMPs-induced membrane perturbation were developed based on
      experiments in liposomes, but their relevance for bacterial killing is debated.
      We determined the association of an analogue of the AMP PMAP-23 to Escherichia
      coli cells, under the same experimental conditions used to measure bactericidal
      activity. Killing took place only when bound peptides completely saturated
      bacterial membranes (10(6)-10(7) bound peptides per cell), indicating that the
      "carpet" model for the perturbation of artificial bilayers is representative of
      what happens in real bacteria. This finding supports the view that, at least for
      this peptide, a microbicidal mechanism is possible in vivo only at micromolar
      total peptide concentrations. We also showed that, notwithstanding their
      simplicity, liposomes represent a reliable model to characterize AMPs partition
      in bacterial membranes. 

PMID- 25058472
TI  - TiO2 nanotube array-graphene-CdS quantum dots composite film in Z-scheme with
      enhanced photoactivity and photostability.
AB  - The most efficient solar energy utilization is achieved in natural photosynthesis
      through elaborate cell membrane with many types of molecules ingeniously
      transferring photogenerated electrons to reactants in a manner similar to the so
      called Z-scheme mechanism. However, artificial photosynthetic systems based on
      semiconductor nanoparticles are inevitably accompanied by undesired non-Z-scheme
      electron transfer and back reactions, which adversely affect the photoactivity
      and photostability of the systems. Herein, we report on a novel Z-scheme system
      with an electrochemically converted graphene (GR) film as the electron mediator
      interlayer contacted with both TiO2 nanotube (TNT) array and CdS quantum dots
      (CdS QDs) on two sides. The obtained TiO2 nanotube array-graphene-CdS quantum
      dots (TNT-GR-CdS) composite film shows higher photoelectric response and
      photocatalytic activities than other bare TNT, TNT-CdS, TNT-GR, and TNT-CdS-GR.
      Moreover, compared to TNT-CdS, the activity stability is significantly improved,
      and the residual amount of Cd element in reaction solution is reduced ~8 times
      over TNT-GR-CdS. Various measurements of photoelectrochemistry and radicals
      reveal that the enhanced photoactivity and photostabilities of TNT-GR-CdS are due
      to the efficient spatial separation of the photogenerated electron-hole pairs and
      the restricted photocorrosion of CdS via an efficient Z-scheme mechanism under
      simulated sunlight. 

PMID- 25058473
TI  - Suicidal ideation among attendees of a West African HIV clinic.
AB  - The paucity of information on suicide and its related issues among people living
      with HIV/AIDS (PLWHA) can impair evidence guided intervention. This study was set
      to determine the prevalence of suicidal ideation and the associated risk factors
      among PLWHA. A total of 295 participants made up of HIV positive individuals were
      subjected to a sociodemographic/clinical profile questionnaire. This was followed
      by the 28-item General Health Questionnaire (GHQ-28), suicidal intention item
      from the Beck Depression Inventory (BDI) and World Health Organisation Quality of
      Life (WHOQOL)--Bref scale to assess emotional distress, suicidal ideation, and
      quality of life respectively. The prevalence of suicidal ideation among PLWHA was
      13.6%; and being unmarried, poor medication adherence, and poorer quality of life
      were significantly associated (p < 0.05) with suicidal ideation; while
      unemployment (odds ratio [OR] = 0.200; 95% Confidence Interval [CI] = 0.084
      0.476; P < 0.001), emotional distress (OR = 5.734; 95% CI = 2.119-15.519; P-
      0.001), religion (OR = 4.829; 95% CI = 1.639-14.231; P--0.004), HIV status non
      disclosure (OR = 2.630; 95% CI = 1.015-6.809; P--0.046) and previous suicidal
      attempt (OR = 0.172, 95% CI = 0.042-0.705; P--0.014) were not only associated but
      predictive of suicidal ideation in PLWHA. These findings indicate a significant
      burden of suicidal ideation, and psychosocial with clinical factors constitute
      identifiable risk factors among PLWHA. The development of evidence guided
      preventive and treatment measures against suicide among PLWHA are implied.

PMID- 25058474
TI  - Novel synthesis of right segment of solanoeclepin A.
AB  - The highly strained tricyclo[5.2.1.0(1,6)]decene skeleton of solanoeclepin A was
      synthesized through two key C-C bond forming processes; thus, a Hg(TFA)2-mediated
      oxymercuration followed an intramolecular aldol reaction to B and a SmI2-mediated
      cyclization of C between an aldehyde and an unsaturated ester to form the
      cyclobutane D having a tricyclo[5.2.1.0(1,6)]dodecene. 

PMID- 25058475
TI  - Apicidin F: characterization and genetic manipulation of a new secondary
      metabolite gene cluster in the rice pathogen Fusarium fujikuroi.
AB  - The fungus F. fujikuroi is well known for its production of gibberellins causing
      the 'bakanae' disease of rice. Besides these plant hormones, it is able to
      produce other secondary metabolites (SMs), such as pigments and mycotoxins.
      Genome sequencing revealed altogether 45 potential SM gene clusters, most of
      which are cryptic and silent. In this study we characterize a new non-ribosomal
      peptide synthetase (NRPS) gene cluster that is responsible for the production of
      the cyclic tetrapeptide apicidin F (APF). This new SM has structural similarities
      to the known histone deacetylase inhibitor apicidin. To gain insight into the
      biosynthetic pathway, most of the 11 cluster genes were deleted, and the mutants
      were analyzed by HPLC-DAD and HPLC-HRMS for their ability to produce APF or new
      derivatives. Structure elucidation was carried out be HPLC-HRMS and NMR analysis.
      We identified two new derivatives of APF named apicidin J and K. Furthermore, we
      studied the regulation of APF biosynthesis and showed that the cluster genes are
      expressed under conditions of high nitrogen and acidic pH in a manner dependent
      on the nitrogen regulator AreB, and the pH regulator PacC. In addition, over
      expression of the atypical pathway-specific transcription factor (TF)-encoding
      gene APF2 led to elevated expression of the cluster genes under inducing and even
      repressing conditions and to significantly increased product yields.
      Bioinformatic analyses allowed the identification of a putative Apf2 DNA-binding
      ("Api-box") motif in the promoters of the APF genes. Point mutations in this
      sequence motif caused a drastic decrease of APF production indicating that this
      motif is essential for activating the cluster genes. Finally, we provide a model
      of the APF biosynthetic pathway based on chemical identification of derivatives
      in the cultures of deletion mutants. 

PMID- 25058476
TI  - Tick-borne encephalitis virus sequenced directly from questing and blood-feeding
      ticks reveals quasispecies variance.
AB  - The increased distribution of the tick-borne encephalitis virus (TBEV) in
      Scandinavia highlights the importance of characterizing novel sequences within
      the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009
      (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were
      sequenced and phylogenetically characterized. Interestingly, the sequence of
      Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly
      virulent Hypr strain, within the 3' non-coding region (3'NCR). A different
      genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis
      demonstrated TBEV variants with different lengths within the poly(A) tract. This
      shows that TBEV quasispecies exists in nature and indicates a putative shift in
      the quasispecies pool when the virus switches between invertebrate and vertebrate
      environments. This prompted us to further sequence and analyze the 3'NCRs of
      additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl.
      Toro 2003 and Habo 2011 contained mainly a short (A)3C(A)6 poly(A) tract. A
      similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944;
      however, one clone of 1991/4944 contained an (A)3C(A)11 poly(A) sequence,
      demonstrating that quasispecies with longer poly(A) could be present in human
      isolates. Neudoerfl has previously been reported to contain a poly(A) region, but
      to our surprise the re-sequenced genome contained two major quasispecies
      variants, both lacking the poly(A) tract. We speculate that the observed
      differences are important factors for the understanding of virulence, spread, and
      control of the TBEV. 

PMID- 25058477
TI  - Presentation of epitope sequences from foreign viruses on the surface of apple
      latent spherical virus particles.
AB  - Apple latent spherical virus (ALSV) has small isometric particles that are
      comprised of two single-stranded RNA species (RNA1 and RNA2) and three capsid
      proteins (Vp25, Vp20, and Vp24). We constructed ALSV vectors for presenting
      foreign peptides on the surface of virus particles. In these vectors, peptides
      can be fused to either of two C-terminal regions of Vp20 (amino acid positions
      between G171 and P172 or between P172 and L173) or the C-terminus (T192) of Vp24.
      An ALSV vector presenting the epitope sequences of the coat protein (CP) of
      zucchini yellow mosaic virus (ZYMV) could systemically infect host plants and was
      specifically recognized by antiserum against ZYMV by ELISA, immunoelectron
      microscopy, and immunoblotting. RT-PCR showed that the epitope sequences up to 20
      amino acids were stably maintained in the chimeric ALSV for more than 10 serial
      passages and at least six months. Purified chimeric ALSV particles induced an
      immune response and the production of antibodies against ZYMV-CP in rabbits. The
      ALSV vector was also used for expression of an epitope from VP1 of foot-and-mouth
      disease virus. 

PMID- 25058478
TI  - Comment on "Airborne trifluoroacetic acid and its fraction from the degradation
      of HFC-134a in Beijing, China".

PMID- 25058479
TI  - Direct oxidative esterification of alcohols.
AB  - Esterification is a fundamental transformation in chemistry. Traditional
      esterification only largely occurs between carboxylic acid derivatives and
      alcohols, and often involves multistep processes. Developments in the transition
      metal-catalysed and metal-free direct esterification of alcohols under oxidative
      conditions has opened a door to the efficient, sustainable and environmentally
      friendly synthesis of esters from readily available materials. This Perspective
      gives an overview which covers the recent development of this emerging field. 

PMID- 25058481
TI  - Routine histological analysis of a macroscopically normal gallbladder--a review
      of the literature.
AB  - BACKGROUND: 70,000 cholecystectomies were performed in the United Kingdom in 2011
      2012. Currently it is standard practice to submit all gallbladder specimens for
      routine histology to exclude malignancy. The aim of this systematic review was to
      establish whether a normal macroscopic appearance to the gallbladder at the time
      of cholecystectomy is sufficient to rule out malignancy and therefore negate the
      need for routine histology. METHODS: Relevant articles that were published
      between 1966 and January 2013 were identified through electronic databases.
      RESULTS: 21 studies reported on 34,499 histologically analysed specimens. 172/187
      (92%) of gallbladder cancers demonstrated intra-operative macroscopic
      abnormality. Studies that opened the specimens intra-operatively identified all
      cancers, whereas gross macroscopic visualization resulted in 15 potentially
      missed cancers (p = 0.10). In patients of European ethnicity, gallbladder cancer
      in a macroscopically normal looking gallbladder was identified in only one study;
      however all of these patients were above the age of 60. The incidence of
      gallbladder cancer was significantly raised in ethnic groups from high risk areas
      (p = 0.0001). CONCLUSIONS: A macroscopically normal gallbladder in patients of
      European ethnicity under the age of 60 may not require formal histopathology. The
      best method for intra-operative examination may involve opening the specimen to
      allow inspection of the mucosa and wall, however this needs further
      investigation. In the context of the volume of gallbladder surgery being
      performed there is the potential for significant cost and time savings.

PMID- 25058480
TI  - Up-regulation of 91H promotes tumor metastasis and predicts poor prognosis for
      patients with colorectal cancer.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) play widespread roles in gene
      regulation and cellular processes. However, the functional roles of lncRNAs in
      colorectal cancer (CRC) are not yet well elucidated. The aim of the present study
      was to measure the levels of lncRNA 91H expression in CRC and evaluate its
      clinical significance and biological roles in the development and progression of
      CRC. METHODS: 91H expression and copy number variation (CNV) were measured in 72
      CRC tumor tissues and adjacent normal tissues by real-time PCR. The biological
      roles of 91H were evaluated by MTT, scratch wound assay, migration and invasion
      assays, and flow cytometry. RESULTS: 91H was significantly overexpressed in
      cancerous tissue and CRC cell lines compared with adjacent normal tissue and a
      normal human intestinal epithelial cell line. Moreover, 91H overexpression was
      closely associated with distant metastasis and poor prognosis in patients with
      CRC, except for CNV of 91H. Multivariate analysis indicated that 91H expression
      was an independent prognostic indicator, as well as distant metastasis. Our in
      vitro data indicated that knockdown of 91H inhibited the proliferation,
      migration, and invasiveness of CRC cells. CONCLUSIONS: 91H played an important
      role in the molecular etiology of CRC and might be regarded as a novel prognosis
      indicator in patients with CRC.

PMID- 25058482
TI  - Reproducibility of spectral-domain optical coherence tomography retinal thickness
      measurements and conversion to equivalent time-domain metrics in diabetic macular
      edema.
AB  - IMPORTANCE: Understanding measurement variability and relationships between
      measurements obtained on different optical coherence tomography (OCT) machines is
      critical for clinical trials and clinical settings. OBJECTIVE: To evaluate the
      reproducibility of retinal thickness measurements from OCT images obtained by
      time-domain (TD) (Stratus; Carl Zeiss Meditec) and spectral-domain (SD) (Cirrus;
      Carl Zeiss Meditec, and Spectralis; Heidelberg Engineering) instruments and
      formulate equations to convert retinal thickness measurements from SD-OCT to
      equivalent values on TD-OCT. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional
      observational study was conducted in private and institutional practices. Persons
      with diabetes mellitus who had at least 1 eye with central-involved diabetic
      macular edema, defined as Stratus central subfield thickness (CST) of 250 MUm or
      greater, participated. An additional normative cohort (individuals with diabetes
      but without diabetic macular edema) was enrolled. Each study eye underwent 2
      replicate Stratus scans followed by 2 replicate Cirrus or Spectralis scans (real
      time image registration used) centered on the fovea. MAIN OUTCOMES AND MEASURES:
      Optical coherence tomography CST and macular volume. RESULTS: The Bland-Altman
      coefficient of repeatability for relative change in CST (the degree of change
      that could be expected from measurement variability) was lower with Spectralis
      (7%) compared with Cirrus (14%) and Stratus (12% and 15% within Cirrus/Stratus
      and Spectralis/Stratus groups, respectively). For each cohort, the initial
      Stratus CST was within 10% of the replicate Stratus measurement nearly all of the
      time; the conversion equations predicted a Stratus CST within 10% of the observed
      thickness 86% and 89% of the time for Cirrus/Stratus and Spectralis/Stratus
      groups, respectively, which is similar to the agreement on Stratus test-retest.
      The Bland-Altman limits of agreement for relative change in CST between machines
      (the degree of change that could be expected from measurement variability
      [combining within and between instrument variability]) were 21% for Cirrus and
      19% for Spectralis when comparing predicted vs actual Stratus measurement.
      CONCLUSIONS AND RELEVANCE: Reproducibility appears to be better with Spectralis
      than with Cirrus and Stratus. Conversion equations to transform Cirrus or
      Spectralis measurements to Stratus-equivalent values, within 10% of the observed
      Stratus thickness values, appear feasible. Central subfield thickness changes
      beyond 10% when using the same machine or 20% when switching machines, after
      conversion to Stratus equivalents, are likely due to a change in retinal
      thickness rather than measurement error.

PMID- 25058483
TI  - The population structure of Vibrio cholerae from the Chandigarh Region of
      Northern India.
AB  - BACKGROUND: Cholera infection continues to be a threat to global public health.
      The current cholera pandemic associated with Vibrio cholerae El Tor has now been
      ongoing for over half a century. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-eight V.
      cholerae El Tor isolates associated with a cholera outbreak in 2009 from the
      Chandigarh region of India were characterised by a combination of microbiology,
      molecular typing and whole-genome sequencing. The genomic analysis indicated that
      two clones of V. cholera circulated in the region and caused disease during this
      time. These clones fell into two distinct sub-clades that map independently onto
      wave 3 of the phylogenetic tree of seventh pandemic V. cholerae El Tor. Sequence
      analyses of the cholera toxin gene, the Vibrio seventh Pandemic Island II (VSPII)
      and SXT element correlated with this phylogenetic position of the two clades on
      the El Tor tree. The clade 2 isolates, characterized by a drug-resistant profile
      and the expression of a distinct cholera toxin, are closely related to the recent
      V. cholerae isolated elsewhere, including Haiti, but fell on a distinct branch of
      the tree, showing they were independent outbreaks. Multi-Locus Sequence Typing
      (MLST) distinguishes two sequence types among the 38 isolates, that did not
      correspond to the clades defined by whole-genome sequencing. Multi-Locus Variable
      length tandem-nucleotide repeat Analysis (MLVA) identified 16 distinct clusters.
      CONCLUSIONS/SIGNIFICANCE: The use of whole-genome sequencing enabled the
      identification of two clones of V. cholerae that circulated during the 2009
      Chandigarh outbreak. These clones harboured a similar structure of ICEVchHai1 but
      differed mainly in the structure of CTX phage and VSPII. The limited capacity of
      MLST and MLVA to discriminate between the clones that circulated in the 2009
      Chandigarh outbreak highlights the value of whole-genome sequencing as a route to
      the identification of further genetic markers to subtype V. cholerae isolates.

PMID- 25058484
TI  - Editorial comment.

PMID- 25058485
TI  - Synergistic antifungal effect of glabridin and fluconazole.
AB  - The incidence of invasive fungal infections is increasing in recent years. The
      present study mainly investigated glabridin (Gla) alone and especially in
      combination with fluconazole (FLC) against Cryptococcus neoformans and Candida
      species (Candida albicans, Candida tropicalis, Candida krusei, Candida
      parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory
      concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that
      Gla possessed a broad-spectrum antifungal activity at relatively high
      concentrations. After combining with FLC, Gla exerted a potent synergistic effect
      against drug-resistant C. albicans and C. tropicalis at lower concentrations when
      interpreted by fractional inhibitory concentration index (FICI). Disk diffusion
      test and time-killing test confirming the synergistic fungicidal effect. Cell
      growth tests suggested that the synergistic effect of the two drugs depended more
      on the concentration of Gla. The cell envelop damage including a significant
      decrease of cell size and membrane permeability increasing were found after Gla
      treatment. Together, our results suggested that Gla possessed a synergistic
      effect with FLC and the cell envelope damage maybe contributed to the synergistic
      effect, which providing new information for developing novel antifungal agents. 

PMID- 25058486
TI  - An organizing function of basement membranes in the developing nervous system.
AB  - The basement membranes (BMs) of the nervous system include (a) the pial BM that
      surrounds the entire CNS, (b) the BMs that outline the vascular system of the CNS
      and PNS and (c) the BMs that are associated with Schwann cells. We previously
      found that isolated BMs are bi-functionally organized, whereby the two surfaces
      have different compositional, biomechanical and cell adhesion properties. To find
      out whether the bi-functional nature of BMs has an instructive function in
      organizing the tissue architecture of the developing nervous system, segments of
      human BMs were inserted into (a) the parasomitic mesoderm of chick embryos,
      intersecting with the pathways of axons and neural crest cells, or (b) into the
      midline of the embryonic chick spinal cord. The implanted BMs integrated into the
      embryonic tissues within 24h and were impenetrable to growing axons and migrating
      neural crests cells. Host axons and neural crest cells contacted the epithelial
      side but avoided the stromal side of the implanted BM. When the BMs were inserted
      into the spinal cord, neurons, glia cells and axons assembled at the epithelial
      side of the implanted BMs, while a connective tissue layer formed at the stromal
      side, resembling the tissue architecture of the spinal cord at the pial surface.
      Since the spinal cord is a-vascular at the time of BM implantation, we propose
      that the bi-functional nature of BMs has the function of segregating epithelial
      and connective cells into two adjacent compartments and participates in
      establishing the tissue architecture at the pial surface of the CNS. 

PMID- 25058487
TI  - Mother-child technique using a novel 4 Fr inner catheter.
AB  - AIMS: The aim of this study was to assess the efficacy of the mother and child
      technique using a 4 Fr inner catheter in coronary angioplasty following the
      failure of conventional techniques. METHODS AND RESULTS: We identified cases in
      which a 4 Fr inner catheter had been used to facilitate stent delivery following
      the failure of conventional techniques. Stent delivery using a 4 Fr inner
      catheter was performed in 30 cases and was successful in 29 cases. Nineteen cases
      for RCA, six cases for LAD and five cases for LCx were examined. Direct
      engagement of a 4 Fr inner catheter was accomplished in eight cases. In the
      remaining patients, deep engagement of a 4 Fr inner catheter was accomplished
      with the anchor technique and/or distal balloon deflation technique. Proximal
      stent delivery followed by distal stent deployment was performed in seven cases
      by using the distal balloon deflation technique in multiple stent deployment.
      There were no complications related to deep intubation of a 4 Fr inner catheter.
      CONCLUSIONS: The use of a 4 Fr inner catheter is safe and highly effective for
      aiding stent delivery. The anchor technique and/or distal balloon deflation
      technique could be required for deep engagement of a 4 Fr inner catheter.

PMID- 25058488
TI  - Large carbon dioxide fluxes from headwater boreal and sub-boreal streams.
AB  - Half of the world's forest is in boreal and sub-boreal ecozones, containing large
      carbon stores and fluxes. Carbon lost from headwater streams in these forests is
      underestimated. We apply a simple stable carbon isotope idea for quantifying the
      CO2 loss from these small streams; it is based only on in-stream samples and
      integrates over a significant distance upstream. We demonstrate that conventional
      methods of determining CO2 loss from streams necessarily underestimate the CO2
      loss with results from two catchments. Dissolved carbon export from headwater
      catchments is similar to CO2 loss from stream surfaces. Most of the CO2
      originating in high CO2 groundwaters has been lost before typical in-stream
      sampling occurs. In the Harp Lake catchment in Canada, headwater streams account
      for 10% of catchment net CO2 uptake. In the Krycklan catchment in Sweden, this
      more than doubles the CO2 loss from the catchment. Thus, even when corrected for
      aquatic CO2 loss measured by conventional methods, boreal and sub-boreal forest
      carbon budgets currently overestimate carbon sequestration on the landscape. 

PMID- 25058489
TI  - A computational study of the respiratory airflow characteristics in normal and
      obstructed human airways.
AB  - Obstructive lung diseases in the lower airways are a leading health concern
      worldwide. To improve our understanding of the pathophysiology of lower airways,
      we studied airflow characteristics in the lung between the 8th and the 14th
      generations using a three-dimensional computational fluid dynamics model, where
      we compared normal and obstructed airways for a range of breathing conditions. We
      employed a novel technique based on computing the Pearson's correlation
      coefficient to quantitatively characterize the differences in airflow patterns
      between the normal and obstructed airways. We found that the airflow patterns
      demonstrated clear differences between normal and diseased conditions for high
      expiratory flow rates (>2300ml/s), but not for inspiratory flow rates. Moreover,
      airflow patterns subjected to filtering demonstrated higher sensitivity than
      airway resistance for differentiating normal and diseased conditions. Further, we
      showed that wall shear stresses were not only dependent on breathing rates, but
      also on the distribution of the obstructed sites in the lung: for the same degree
      of obstruction and breathing rate, we observed as much as two-fold differences in
      shear stresses. In contrast to previous studies that suggest increased wall shear
      stress due to obstructions as a possible damage mechanism for small airways, our
      model demonstrated that for flow rates corresponding to heavy activities, the
      wall shear stress in both normal and obstructed airways was <0.3Pa, which is
      within the physiological limit needed to promote respiratory defense mechanisms.
      In summary, our model enables the study of airflow characteristics that may be
      impractical to assess experimentally. 

PMID- 25058490
TI  - Harbor seals (Phoca vitulina) can perceive optic flow under water.
AB  - Optic flow, the pattern of apparent motion elicited on the retina during
      movement, has been demonstrated to be widely used by animals living in the aerial
      habitat, whereas underwater optic flow has not been intensively studied so far.
      However optic flow would also provide aquatic animals with valuable information
      about their own movement relative to the environment; even under conditions in
      which vision is generally thought to be drastically impaired, e. g. in turbid
      waters. Here, we tested underwater optic flow perception for the first time in a
      semi-aquatic mammal, the harbor seal, by simulating a forward movement on a
      straight path through a cloud of dots on an underwater projection. The
      translatory motion pattern expanded radially out of a singular point along the
      direction of heading, the focus of expansion. We assessed the seal's accuracy in
      determining the simulated heading in a task, in which the seal had to judge
      whether a cross superimposed on the flow field was deviating from or congruent
      with the actual focus of expansion. The seal perceived optic flow and determined
      deviations from the simulated heading with a threshold of 0.6 deg of visual
      angle. Optic flow is thus a source of information seals, fish and most likely
      aquatic species in general may rely on for e. g. controlling locomotion and
      orientation under water. This leads to the notion that optic flow seems to be a
      tool universally used by any moving organism possessing eyes. 

PMID- 25058492
TI  - Including pathogen risk in life cycle assessment of wastewater management. 1.
      Estimating the burden of disease associated with pathogens.
AB  - The environmental performance of wastewater and sewage sludge management is
      commonly assessed using life cycle assessment (LCA), whereas pathogen risk is
      evaluated with quantitative microbial risk assessment (QMRA). This study explored
      the application of QMRA methodology with intent to include pathogen risk in LCA
      and facilitate a comparison with other potential impacts on human health
      considered in LCA. Pathogen risk was estimated for a model wastewater treatment
      system (WWTS) located in an industrialized country and consisting of primary,
      secondary, and tertiary wastewater treatment, anaerobic sludge digestion, and
      land application of sewage sludge. The estimation was based on eight previous
      QMRA studies as well as parameter values taken from the literature. A total
      pathogen risk (expressed as burden of disease) on the order of 0.2-9 disability
      adjusted life years (DALY) per year of operation was estimated for the model WWTS
      serving 28,600 persons and for the pathogens and exposure pathways included in
      this study. The comparison of pathogen risk with other potential impacts on human
      health considered in LCA is detailed in part 2 of this article series.

PMID- 25058491
TI  - A meta-analysis of parental smoking and the risk of childhood brain tumors.
AB  - OBJECTIVE: Previous studies regarding the association between parental smoking
      and the risk of childhood brain tumors (CBT) have reported inconsistent results.
      We performed a meta-analysis to summarize evidence on this association and to
      quantify the potential dose-response relationship. METHODS: A systematic
      literature search was conducted in the Medline and Embase databases. The summary
      relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Dose
      response meta-analysis was also performed for studies that reported categorical
      risk estimates for a series of smoking exposure levels. RESULTS: A total of 17
      studies fulfilled the inclusion criteria. In the meta-analyses, the summary RRs
      (95% CIs) of CBT for maternal smoking during pregnancy, paternal smoking during
      pregnancy, maternal smoking before pregnancy, and paternal smoking before
      pregnancy were 0.96 (0.86-1.07), 1.09 (0.97-1.22), 0.93 (0.85-1.00), and 1.09
      (1.00-1.20), respectively. Dose-response meta-analysis also showed no significant
      association between parental smoking and the risk of CBT. CONCLUSIONS: Findings
      from our meta-analysis indicate that parental smoking may not be associated with
      a risk of CBT.

PMID- 25058493
TI  - CO oxidation catalyzed by Pt-embedded graphene: a first-principles investigation.
AB  - We addressed the potential catalytic role of Pt-embedded graphene in CO oxidation
      by first-principles-based calculations. We showed that the combination of highly
      reactive Pt atoms and defects over graphene makes the Pt-embedded graphene a
      superior mono-dispersed atomic catalyst for CO oxidation. The binding energy of a
      single Pt atom onto monovacancy defects is up to -7.10 eV, which not only ensures
      the high stability of the embedded Pt atom, but also vigorously excludes the
      possibility of diffusion and aggregation of embedded Pt atoms. This strong
      interfacial interaction also tunes the energy level of Pt-d states for the
      activation of O2, and promotes the formation and dissociation of the peroxide
      like intermediate. The catalytic cycle of CO oxidation is initiated through the
      Langmuir-Hinshelwood mechanism, with the formation of a peroxide-like
      intermediate by the coadsorbed CO and O2, by the dissociation of which the CO2
      molecule and an adsorbed O atom are formed. Then, another gaseous CO will react
      with the remnant O atom and make the embedded Pt atom available for the
      subsequent reaction. The calculated energy barriers for the formation and
      dissociation of the peroxide-like intermediate are as low as 0.33 and 0.15 eV,
      respectively, while that for the regeneration of the embedded Pt atom is 0.46 eV,
      indicating the potential high catalytic performance of Pt-embedded graphene for
      low temperature CO oxidation. 

PMID- 25058494
TI  - Self-unawareness of levodopa induced dyskinesias in patients with Parkinson's
      disease.
AB  - The study analyzes the presence of dyskinesias-reduced-self-awareness in forty
      eight patients suffering from Parkinson's disease (PD). As the association with
      executive dysfunction is a matter of debate and we hypothesize it plays an
      important role in dyskinesias self-unawareness, we analyzed the role of
      dopaminergic treatment on the medial-prefrontal-ventral-striatal circuitry using
      a neurocognitive approach. Special attention was given to metacognitive abilities
      related to action-monitoring that represent a novel explanation of the
      phenomenon. PD patients were assessed using different rating scales that we
      devised to measure movement awareness disorders. In order to ascertain whether
      each variable measured at a cognitive-clinical level contributes to predicting
      the scores of the movement-disorder-awareness-scales, we conducted multiple
      logistic regression models using the latter as binary dependent variables. We
      used the Wisconsin Card Sorting Test-metacognitive-version to assess the
      executive functions of the prefrontal-ventral-striatal circuitry. Data showed
      that a reduction of self-awareness using the Dyskinesia rating scale was
      associated with global monitoring (p=.04), monitoring resolution (p=.04) and
      control sensitivity (p=.04). Patients failed to perceive their performance,
      distinguish between correct and incorrect sorts, be confident in their choice and
      consequently decide to gamble during the task. We did not find any association
      with executive functions using the hypo-bradykinesia rating scale. Our findings
      indicate that when the comparator mechanism for monitoring attentive performance
      is compromised at a prefrontal striatal level, patients lose the ability to
      recognize their motor disturbances that do not achieve conscious awareness. 

PMID- 25058495
TI  - Detecting concealed information using feedback related event-related brain
      potentials.
AB  - Employing an event-related potential (ERP)-based concealed information test
      (CIT), the present study investigated (1) the neurocognitive processes when
      people received feedbacks regarding their deceptive/truthful responses and (2)
      whether such feedback-related ERP activities can be used to detect concealed
      information above and beyond the recognition-related P300. During the CIT,
      participants were presented with rare, meaningful probes (their own names)
      embedded within a series of frequent yet meaningless irrelevants (others' names).
      Participants were instructed to deny their recognition of the probes. Critically,
      following participants' responses, they were provided with feedbacks regarding
      whether they succeeded or failed in the CIT. Replicating previous ERP-based CITs,
      we found a larger P300 elicited by probe compared to irrelevant. Regarding
      feedback-related ERPs, a temporospatial Principle Component Analyses found two
      ERP components that were not only sensitive to feedback manipulations but also
      can discriminate probe from irrelevant: an earlier, central-distributed
      positivity that was elicited by "success" feedbacks peaked around 219ms; and a
      later, right central-distributed positivity that was also elicited by "success"
      feedbacks, peaked around 400ms. Importantly, the feedback ERPs were not
      correlated with P300 that was elicited by probe/irrelevant, suggesting that these
      two ERPs reflect independent processes underlying memory concealment. These
      findings illustrate the feasibility and promise of using feedback-related ERPs to
      detect concealed memory and thus deception. 

PMID- 25058496
TI  - An intronic microRNA links Rb/E2F and EGFR signaling.
AB  - The importance of microRNAs in the regulation of various aspects of biology and
      disease is well recognized. However, what remains largely unappreciated is that a
      significant number of miRNAs are embedded within and are often co-expressed with
      protein-coding host genes. Such a configuration raises the possibility of a
      functional interaction between a miRNA and the gene it resides in. This is
      exemplified by the Drosophila melanogaster dE2f1 gene that harbors two miRNAs,
      mir-11 and mir-998, within its last intron. miR-11 was demonstrated to limit the
      proapoptotic function of dE2F1 by repressing cell death genes that are directly
      regulated by dE2F1, however the biological role of miR-998 was unknown. Here we
      show that one of the functions of miR-998 is to suppress dE2F1-dependent cell
      death specifically in rbf mutants by elevating EGFR signaling. Mechanistically,
      miR-998 operates by repressing dCbl, a negative regulator of EGFR signaling.
      Significantly, dCbl is a critical target of miR-998 since dCbl phenocopies the
      effects of miR-998 on dE2f1-dependent apoptosis in rbf mutants. Importantly, this
      regulation is conserved, as the miR-998 seed family member miR-29 repressed c
      Cbl, and enhanced MAPK activity and wound healing in mammalian cells. Therefore,
      the two intronic miRNAs embedded in the dE2f1 gene limit the apoptotic function
      of dE2f1, but operate in different contexts and act through distinct mechanisms.
      These results also illustrate that examining an intronic miRNA in the context of
      its host's function can be valuable in elucidating the biological function of the
      miRNA, and provide new information about the regulation of the host gene itself. 

PMID- 25058497
TI  - Incidence and predictors of multimorbidity in the elderly: a population-based
      longitudinal study.
AB  - BACKGROUND: We aimed to calculate 3-year incidence of multimorbidity, defined as
      the development of two or more chronic diseases in a population of older people
      free from multimorbidity at baseline. Secondly, we aimed to identify predictors
      of incident multimorbidity amongst life-style related indicators, medical
      conditions and biomarkers. METHODS: Data were gathered from 418 participants in
      the first follow up of the Kungsholmen Project (Stockholm, Sweden, 1991-1993, 78+
      years old) who were not affected by multimorbidity (149 had none disease and 269
      one disease), including a social interview, a neuropsychological battery and a
      medical examination. RESULTS: After 3 years, 33.6% of participants who were
      without disease and 66.4% of those with one disease at baseline, developed
      multimorbidity: the incidence rate was 12.6 per 100 person-years (95% CI: 9.2
      16.7) and 32.9 per 100 person-years (95% CI: 28.1-38.3), respectively. After
      adjustments, worse cognitive function (OR, 95% CI, for 1 point lower Mini-Mental
      State Examination: 1.22, 1.00-1.48) was associated with increased risk of
      multimorbidity among subjects with no disease at baseline. Higher age was the
      only predictor of multimorbidity in persons with one disease at baseline.
      CONCLUSIONS: Multimorbidity has a high incidence at old age. Mental health
      related symptoms are likely predictors of multimorbidity, suggesting a strong
      impact of mental disorders on the health of older people.

PMID- 25058498
TI  - Effect of binasal occlusion (BNO) and base-in prisms on the visual-evoked
      potential (VEP) in mild traumatic brain injury (mTBI).
AB  - PURPOSE: To assess quantitatively the effect and relative contribution of binasal
      occlusion (BNO) and base-in prisms (BI) on visually-evoked potential (VEP)
      responsivity in persons with mild traumatic brain injury (mTBI) and the symptom
      of visual motion sensitivity (VMS), as well as in visually-normal (VN)
      individuals. RESEARCH DESIGN AND METHODS: Subjects were comprised of 20 VN adults
      and 15 adults with mTBI and VMS. There were four test conditions: (1)
      conventional pattern VEP, which served as the baseline comparison condition; (2)
      VEP with BNO alone; (3) VEP with 2 pd BI prisms before each eye; and (4) VEP with
      the above BNO and BI prism combination. RESULTS: In mTBI, the mean VEP amplitude
      increased significantly in nearly all subjects (~90%) with BNO alone. In
      contrast, in VN, it decreased significantly with BNO alone in all subjects
      (100%), as compared to the other test conditions. These objective findings were
      consistent with improvements in visual impressions and sensorimotor tasks in the
      group with mTBI. Latency remained within normal limits under all test conditions
      in both groups. CONCLUSIONS: Only the BNO condition demonstrated significant, but
      opposite and consistent, directional effects on the VEP amplitude in both groups.
      The BNO-VEP test condition may be used clinically for the objectively-based,
      differential diagnosis of persons suspected of having mTBI and VMS from the VNs.

PMID- 25058499
TI  - Evidence for autism spectrum disorder in Jacobsen syndrome: identification of a
      candidate gene in distal 11q.
AB  - PURPOSE: Jacobsen syndrome, also called the 11q terminal deletion disorder, is a
      contiguous gene disorder caused by the deletion of the end of the long arm of
      chromosome 11. Intellectual skills range from low average to severe/profound
      intellectual disability and usually correlate with deletion size. Comprehensive
      genotype/phenotype evaluations are limited, and little is known about specific
      behavioral characteristics associated with 11q terminal deletion disorder.
      METHODS: In this prospective study, 17 patients with 11q terminal deletion
      disorder underwent cognitive and behavioral assessments. Deletion sizes were
      determined by array comparative genomic hybridization. RESULTS: Deletion sizes
      ranged from 8.7 to 14.5 Mb across the patients. We found that 8 of 17 patients
      (47%) exhibited behavioral characteristics consistent with an autism spectrum
      disorder diagnosis. There was no correlation between deletion size and the
      presence of autism spectrum disorder, implicating at least one predisposing gene
      in the distal 8.7 Mb of 11q. The findings from three additional patients with
      autistic features and "atypical" distal 11q deletions led to the identification
      of an autism "critical region" in distal 11q containing four annotated genes
      including ARHGAP32 (also known as RICS), a gene encoding rho GTPase activating
      protein. CONCLUSION: Results from this study support early autism spectrum
      disorder screening for patients with 11q terminal deletion disorder and provide
      further molecular insights into the pathogenesis of autism spectrum disorder.

PMID- 25058500
TI  - Whole-exome sequencing identifies rare pathogenic variants in new predisposition
      genes for familial colorectal cancer.
AB  - PURPOSE: Colorectal cancer is an important cause of mortality in the developed
      world. Hereditary forms are due to germ-line mutations in APC, MUTYH, and the
      mismatch repair genes, but many cases present familial aggregation but an unknown
      inherited cause. The hypothesis of rare high-penetrance mutations in new genes is
      a likely explanation for the underlying predisposition in some of these familial
      cases. METHODS: Exome sequencing was performed in 43 patients with colorectal
      cancer from 29 families with strong disease aggregation without mutations in
      known hereditary colorectal cancer genes. Data analysis selected only very rare
      variants (0-0.1%), producing a putative loss of function and located in genes
      with a role compatible with cancer. Variants in genes previously involved in
      hereditary colorectal cancer or nearby previous colorectal cancer genome-wide
      association study hits were also chosen. RESULTS: Twenty-eight final candidate
      variants were selected and validated by Sanger sequencing. Correct family
      segregation and somatic studies were used to categorize the most interesting
      variants in CDKN1B, XRCC4, EPHX1, NFKBIZ, SMARCA4, and BARD1. CONCLUSION: We
      identified new potential colorectal cancer predisposition variants in genes that
      have a role in cancer predisposition and are involved in DNA repair and the cell
      cycle, which supports their putative involvement in germ-line predisposition to
      this neoplasm.

PMID- 25058501
TI  - Gorgan (Turkmen in Iran) HLA genetics: transplantation, pharmacogenomics and
      anthropology.
AB  - HLA class I and II alleles have been studied in a population from Gorgan (North
      East Iranian city bordering Turkmenistan). This population is composed of mainly
      Turkmen who speak Oghuz Turkish language. Comparison of Gorgan people HLA profile
      has been carried out with about 7984 HLA chromosomes from other worldwide
      populations; extended haplotypes and three dimension genetic distances have been
      calculated by using neighbor-joining and correspondence relatedness analyses.
      Most frequent extended HLA haplotypes show a Siberian/Mediterranean admixture and
      closest populations are Chuvashians (North Caspian Sea, Russia) and other
      geographically close populations like Siberian Mansi, Buryats and other Iranians.
      New extended HLA haplotypes have been found, such as: A*31:01-B*35:01-DRB1*15:01
      DQB1*03:01, A*01:01-B*35:01-DRB1*03:01-DQB1*02:01. Relationships of Turkmen with
      Kurgan (Gorgan) archaeological mounds, Scythians and Sarmatians are discussed.
      This study is also useful for a future transplantation Gorgan waiting list,
      Gorgan HLA and disease epidemiology and HLA pharmacogenomics. 

PMID- 25058502
TI  - Pedunculopontine tegmental nucleus neurons provide reward, sensorimotor, and
      alerting signals to midbrain dopamine neurons.
AB  - Dopamine (DA) neurons in the midbrain are crucial for motivational control of
      behavior. However, recent studies suggest that signals transmitted by DA neurons
      are heterogeneous. This may reflect a wide range of inputs to DA neurons, but
      which signals are provided by which brain areas is still unclear. Here we focused
      on the pedunculopontine tegmental nucleus (PPTg) in macaque monkeys and
      characterized its inputs to DA neurons. Since the PPTg projects to many brain
      areas, it is crucial to identify PPTg neurons that project to DA neuron areas.
      For this purpose we used antidromic activation technique by electrically
      stimulating three locations (medial, central, lateral) in the substantia nigra
      pars compacta (SNc). We found SNc-projecting neurons mainly in the PPTg, and some
      in the cuneiform nucleus. Electrical stimulation in the SNc-projecting PPTg
      regions induced a burst of spikes in presumed DA neurons, suggesting that the
      PPTg-DA (SNc) connection is excitatory. Behavioral tasks and clinical tests
      showed that the SNc-projecting PPTg neurons encoded reward, sensorimotor and
      arousal/alerting signals. Importantly, reward-related PPTg neurons tended to
      project to the medial and central SNc, whereas sensorimotor/arousal/alerting
      related PPTg neurons tended to project to the lateral SNc. Most reward-related
      signals were positively biased: excitation and inhibition when a better and worse
      reward was expected, respectively. These PPTg neurons tended to retain the reward
      value signal until after a reward outcome, representing 'value state'; this was
      different from DA neurons which show phasic signals representing 'value change'.
      Our data, together with previous studies, suggest that PPTg neurons send positive
      reward-related signals mainly to the medial-central SNc where DA neurons encode
      motivational values, and sensorimotor/arousal signals to the lateral SNc where DA
      neurons encode motivational salience. 

PMID- 25058504
TI  - Standards for definitions and use of outcome measures for clinical effectiveness
      research in perioperative medicine: European Perioperative Clinical Outcome
      (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on
      perioperative outcome measures.
AB  - There is a need for large trials that test the clinical effectiveness of
      interventions in the field of perioperative medicine. Clinical outcome measures
      used in such trials must be robust, clearly defined and patient-relevant. Our
      objective was to develop standards for the use of clinical outcome measures to
      strengthen the methodological quality of perioperative medicine research. A
      literature search was conducted using PubMed and opinion leaders worldwide were
      invited to nominate papers that they believed the group should consider. The full
      texts of relevant articles were reviewed by the taskforce members and then
      discussed to reach a consensus on the required standards. The report was then
      circulated to opinion leaders for comment and review. This report describes
      definitions for 22 individual adverse events with a system of severity grading
      for each. In addition, four composite outcome measures were identified, which
      were designed to evaluate postoperative outcomes. The group also agreed on
      standards for four outcome measures for the evaluation of healthcare resource use
      and quality of life. Guidance for use of these outcome measures is provided, with
      particular emphasis on appropriate duration of follow-up. This report provides
      clearly defined and patient-relevant outcome measures for large clinical trials
      in perioperative medicine. These outcome measures may also be of use in clinical
      audit. This report is intended to complement and not replace other related work
      to improve assessment of clinical outcomes following specific surgical
      procedures. 

PMID- 25058503
TI  - Analysis of candidate genes for morphine preference quantitative trait locus
      Mop2.
AB  - Compared to DBA/2J (D2), C57BL/6J (B6) inbred mice exhibit strong morphine
      preference when tested using a two-bottle choice drinking paradigm. A morphine
      preference quantitative trait locus (QTL), Mop2, was originally mapped to
      proximal chromosome (Chr) 10 using a B6xD2 F2 intercross population, confirmed
      with reciprocal congenic strains and fine mapped with recombinant congenic
      strains. These efforts identified a ~ 10-Million base pair (Mbp) interval,
      underlying Mop2, containing 35 genes. To further reduce the interval, mice from
      the D2.B6-Mop2-P1 congenic strain were backcrossed to parental D2 mice and two
      new recombinant strains of interest were generated: D2.B6-Mop2-P1.pD.dB and D2.B6
      Mop2-P1.pD.dD. Results obtained from testing these strains in the two-bottle
      choice drinking paradigm suggest that the gene(s) responsible for the Mop2 QTL is
      one or more of 22 remaining within the newly defined interval (~ 7.6 Mbp) which
      includes Oprm1 and several other genes related to opioid pharmacology. Real-time
      qRT-PCR analysis of Oprm1 and opioid-related genes Rgs17, Ppp1r14c, Vip, and Iyd
      revealed both between-strain and within-strain expression differences in
      comparisons of saline- and morphine-treated B6 and D2 mice. Analysis of Rgs17
      protein levels also revealed both between-strain and within-strain differences in
      comparisons of saline- and morphine-treated B6 and D2 mice. Results suggest that
      the Mop2 QTL represents the combined influence of multiple genetic variants on
      morphine preference in these two strains. Relative contributions of each variant
      remain to be determined.

PMID- 25058505
TI  - Can aging in place be cost effective? A systematic review.
AB  - PURPOSE OF THE STUDY: To systematically review cost, cost-minimization and cost
      effectiveness studies for assisted living technologies (ALTs) that specifically
      enable older people to 'age in place' and highlight what further research is
      needed to inform decisions regarding aging in place. DESIGN: People aged 65+ and
      their live-in carers (where applicable), using an ALT to age in place at home
      opposed to a community-dwelling arrangement. METHODS: Studies were identified
      using a predefined search strategy on two key economic and cost evaluation
      databases NHS EED, HEED. Studies were assessed using methods recommended by the
      Campbell and Cochrane Economic Methods Group and presented in a narrative
      synthesis style. RESULTS: Eight eligible studies were identified from North
      America spread over a diverse geographical range. The majority of studies
      reported the ALT intervention group as having lower resource use costs than the
      control group; though the low methodological quality and heterogeneity of the
      individual costs and outcomes reported across studies must be considered.
      IMPLICATIONS: The studies suggest that in some cases ALTs may reduce costs,
      though little data were identified and what there were was of poor quality.
      Methods to capture quality of life gains were not used, therefore potential
      effects on health and wellbeing may be missed. Further research is required using
      newer developments such as the capabilities approach. High quality studies
      assessing the cost-effectiveness of ALTs for ageing in place are required before
      robust conclusion on their use can be drawn.

PMID- 25058506
TI  - Membrane interaction of bound ligands contributes to the negative binding
      cooperativity of the EGF receptor.
AB  - The epidermal growth factor receptor (EGFR) plays a key role in regulating cell
      proliferation, migration, and differentiation, and aberrant EGFR signaling is
      implicated in a variety of cancers. EGFR signaling is triggered by extracellular
      ligand binding, which promotes EGFR dimerization and activation. Ligand-binding
      measurements are consistent with a negatively cooperative model in which the
      ligand-binding affinity at either binding site in an EGFR dimer is weaker when
      the other site is occupied by a ligand. This cooperativity is widely believed to
      be central to the effects of ligand concentration on EGFR-mediated intracellular
      signaling. Although the extracellular portion of the human EGFR dimer has been
      resolved crystallographically, the crystal structures do not reveal the
      structural origin of this negative cooperativity, which has remained unclear.
      Here we report the results of molecular dynamics simulations suggesting that
      asymmetrical interactions of the two binding sites with the membrane may be
      responsible (perhaps along with other factors) for this negative cooperativity.
      In particular, in our simulations the extracellular domains of an EGFR dimer
      spontaneously lay down on the membrane in an orientation in which favorable
      membrane contacts were made with one of the bound ligands, but could not be made
      with the other. Similar interactions were observed when EGFR was glycosylated, as
      it is in vivo. 

PMID- 25058508
TI  - The transcription elongation factor ELL2 is specifically upregulated in HTLV-1
      infected T-cells and is dependent on the viral oncoprotein Tax.
AB  - The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent
      transactivator of viral and cellular transcription. Here, we identified ELL2 as
      the sole transcription elongation factor to be specifically upregulated in HTLV-1
      /Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient
      transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter,
      and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes.
      However, we also measured upregulation of ELL2 in HTLV-1-transformed cells
      exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be
      maintained independent of continuous Tax expression. We further show that Tax and
      ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2
      cooperates with Tax in viral transactivation. This is supported by our findings
      that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate
      upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2
      could contribute to HTLV-1 gene regulation. 

PMID- 25058507
TI  - Amiloride inhibits the initiation of Coxsackievirus and poliovirus RNA
      replication by inhibiting VPg uridylylation.
AB  - The mechanism of amiloride inhibition of Coxsackievirus B3 (CVB3) and poliovirus
      type 1 (PV1) RNA replication was investigated using membrane-associated RNA
      replication complexes. Amiloride was shown to inhibit viral RNA replication and
      VPgpUpU synthesis. However, the drug had no effect on polymerase elongation
      activity during either (-) strand or (+) strand synthesis. These findings
      indicated that amiloride inhibited the initiation of RNA synthesis by inhibiting
      VPg uridylylation. In addition, in silico binding studies showed that amiloride
      docks in the VPg binding site on the back of the viral RNA polymerase, 3D(pol).
      Since VPg binding at this site on PV1 3D(pol) was previously shown to be required
      for VPg uridylylation, our results suggest that amiloride inhibits VPg binding to
      3D(pol). In summary, our findings are consistent with a model in which amiloride
      inhibits VPgpUpU synthesis and viral RNA replication by competing with VPg for
      binding to 3D(pol). 

PMID- 25058509
TI  - Genetic structure in a progenetic trematode: signs of cryptic species with
      contrasting reproductive strategies.
AB  - Complexes of cryptic species are rapidly being discovered in many parasite taxa,
      including trematodes. However, after they are found, cryptic species are rarely
      distinguished from each other with respect to key ecological or life history
      traits. In this study, we applied an integrative taxonomic approach to the
      discovery of cryptic species within Stegodexamene anguillae, a facultatively
      progenetic trematode common throughout New Zealand. The presence of cryptic
      species was determined by the genetic divergence found in the mitochondrial
      cytochrome c oxidase I gene, the 16S rRNA gene and the nuclear 28S gene,
      warranting recognition of two distinct species and indicating a possible third
      species. Speciation was not associated with geographic distribution or
      microhabitat within the second intermediate host; however frequency of the
      progenetic reproductive strategy (and the truncated life cycle associated with
      it) was significantly greater in one of the lineages. Therefore, two lines of
      evidence, molecular and ecological, support the distinction between these two
      species and suggest scenarios for their divergence. 

PMID- 25058510
TI  - Neuropeptidergic control of the hindgut in the black-legged tick Ixodes
      scapularis.
AB  - The hindgut, as a part of the tick excretory system, plays an important
      physiological role in maintaining homoeostases and waste elimination.
      Immunoreactive projections from the synganglion to the hindgut were found using
      antibodies against four different neuropeptides: FGLamide related allatostatin,
      myoinhibitory peptide, SIFamide, and orcokinin. The presence of FGLamide related
      allatostatin, myoinhibitory peptide and SIFamide in both synganglia (source) and
      hindgut (target organ) extracts was confirmed by MALDI-TOF. Tissue-specific PCR
      revealed the expression of four putative FGLamide related allatostatin receptors
      and an SIFamide receptor in the hindgut. An antibody against Ixodes scapularis
      SIFamide receptor detected immunoreactive spots in epithelial cells as well as
      the visceral muscles surrounding the rectal sac, while staining with the antibody
      against myoinhibitory peptide receptor 1 revealed that the immunoreactivity was
      only associated with the visceral muscles. In hindgut motility assays, SIFamide
      activated hindgut motility in a dose-dependent manner. None of other three
      neuropeptides (FGLamide related allatostatin, myoinhibitory peptide and
      orcokinin) activated hindgut motility when tested alone. Myoinhibitory peptide
      antagonised the SIFamide-stimulated hindgut mobility when it was tested in
      combination with SIFamide.

PMID- 25058511
TI  - Hc-fau, a novel gene regulating diapause in the nematode parasite Haemonchus
      contortus.
AB  - Diapause induced in the early fourth stage of Haemonchus contortus is a strategy
      to adapt this nematode to hostile environmental conditions. In this study, we
      identified a new gene, Hc-fau, a homologue of human fau and Caenorhabditis
      elegans Ce-rps30. Hc-fau encodes two proteins through alternative RNA splicing,
      Hc-FAUA and Hc-FAUB, consisting of 130 and 107 amino acids, respectively. Hc-FAU
      possesses a diverged ubiquitin-like (UBiL) protein domain and a conserved
      ribosome protein S30 domain. The protein is ubiquitously expressed, except in the
      gonad. However Hc-fau transcripts decrease significantly in diapausing L4s of H.
      contortus. In C. elegans, knockdown of Ce-rps30 confers an extended lifespan,
      increased lipid storage in the intestine and shortened body length. These
      morphological characteristics are comparable with dauer larvae of C. elegans, in
      which the gonad is condensed considerably. In contrast, a shortened lifespan is
      observed in C. elegans over-expressing Hc-faua, and especially Hc-faub, with
      hatching failure detected. The genes of insulin/IGF-1 signalling (IIS), TGF-beta,
      cGMP, dafachronic acid (DA), apoptosis (AP) and fatty acids (FA) metabolism are
      all down-regulated in Ce-rps30RNAi (RNA interference) worms, except for akt-1 and
      daf-16. However, daf-16 up-regulation is inconsistent with its target gene down
      regulation and the result from a heat stress assay in these worms. Daf-16 RNAi
      conducted in Ce-rps30 (tm6034/nt1) mutants failed to rescue the worms. The S30
      domain stays in the nucleus, while UBiL accumulates in the cytoplasm. Compared
      with Hc-FAUA, results of UBiL domain and S30 domain over-expression indicate
      synergism between UBiL and S30 in regulating lifespan and reproduction. These
      results suggest the potential functions of Hc-fau in regulating larval diapause
      in H.contortus. 

PMID- 25058513
TI  - Microbial degradation of 2,4-dichlorophenoxyacetic acid: Insight into the enzymes
      and catabolic genes involved, their regulation and biotechnological implications.
AB  - A considerable progress has been made to understand the mechanisms of
      biodegradation of 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D biodegradation
      pathway has been elucidated in many microorganisms including Cupriavidus necator
      JMP134 (previously known as Wautersia eutropha, Ralstonia eutropha and
      Alcaligenes eutrophus) and Pseudomonas strains. It generally involves the side
      chain removal of 2,4-D by alpha-ketoglutarate-dependent 2,4-D dioxygenase (tfdA)
      to form 2,4-dichlorophenol (2,4-DCP); hydroxylation of 2,4-DCP by 2,4-DCP
      hydroxylase (tfdB) to form dichlorocatechol; ortho or meta cleavage of
      dichlorocatechol by chlorocatechol 1,2-dioxygenase (tfdC) to form 2,4-dichloro
      cis,cis-muconate; conversion of 2,4-dichloro-cis,cis-muconate to 2
      chlorodienelactone by chloromuconate cycloisomerase (tfdD); conversion of 2
      chlorodienelactone to 2-chloromaleylacetate by chlorodienelactone hydrolase
      (tfdE) and, finally, conversion of 2-chloromaleylacetate to 3-oxoadepate via
      maleylacetate by chloromaleylacetate reductase and maleylacetate reductase
      (tfdF), respectively, which is funnelled to the tricarboxylic acid cycle. The
      latest review on microbial breakdown of 2,4-D, other halogenated aromatic
      pesticides, and related compounds was compiled by Haggblom, however, a
      considerable progress has been made in this area of research since then. Thus,
      this review focuses on the recent advancement on 2,4-D biodegradation, the
      enzymes, and genes involved and their biotechlogical implications. 

PMID- 25058512
TI  - Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in
      mouse neuropathic and inflammatory pain models.
AB  - Common pharmacological treatments of neuropathic and chronic inflammatory pain
      conditions generally lack efficacy and/or are associated with significant
      untoward side effects. However, recent preclinical data indicate that combined
      inhibition of cyclooxygenase (COX) and fatty acid amide hydrolase (FAAH), the
      primary catabolic enzyme of the endocannabinoid N-arachidonoylethanolamine
      (anandamide; AEA), produces enhanced antinociceptive effects in a variety of
      murine models of pain. Accordingly, the primary objective of the present study
      was to investigate the consequences of co-administration of the COX inhibitor
      diclofenac and the highly selective FAAH inhibitor PF-3845 in models of
      neuropathic pain (i.e., chronic constrictive injury of the sciatic nerve (CCI))
      and inflammatory pain induced by an intraplantar injection of carrageenan. Here,
      we report that combined administration of subthreshold doses of these drugs
      produced enhanced antinociceptive effects in CCI and carrageenan pain models, the
      latter of which was demonstrated to require both CB1 and CB2 receptors. The
      combined administration of subthreshold doses of these drugs also increased AEA
      levels and decreased prostaglandin levels in whole brain. Together, these data
      add to the growing research that dual blockade of FAAH and COX represents a
      potential therapeutic strategy for the treatment of neuropathic and inflammatory
      pain states. PERSPECTIVE: Tandem inhibition of FAAH and COX attenuates
      inflammatory and neuropathic pain states, which may avoid potentially harmful
      side effects of other therapeutic options, such as NSAIDs or opioids.

PMID- 25058514
TI  - The Eurasian genes of the 2009 pandemic influenza virus: an integrative
      perspective on their conveyance to and assimilation in America.
AB  - The formation of pandemic influenza genotypes varied phylogeographically and
      ecophylogenetically throughout their fully recognized recent 100-years natural
      history, involving consistently avian plus human genes, and at times swine genes.
      The last four traceable pandemic strains (PSs) included two American H1N1 viruses
      with genomes predominantly containing swine genes, of which at least one genome
      originated from both America and Eurasia; and two non-H1N1 Asian viruses with
      genomes entirely originating from Asia, and having no swine genes. This study
      explores whether there is a particular interhemispheric system underlying such
      divergence, and its properties. Unlike the assumption that transport of live pigs
      from Eurasia to America facilitated the formation of the 2009 H1N1 PS in America,
      it is suggested that conveyance of Eurasian swine genes to America, and their
      assimilation therein, took place through a distinct, perfectly natural
      ecophylogenetic machinery. The latter conjunctively involves, foremost, a native
      Asian duck-swine-man interface, a Holarctic chain of certain migratory Anas
      ducks, a native American turkey-swine-man interface, and two specific clades of
      American influenza A viruses. Likewise, the described machinery could have
      readily given rise to the 1918 H1N1, and, presumably, earlier American PSs,
      altogether constituting private cases of a much broader, self-sustained,
      permanent phylogeographic system. 

PMID- 25058525
TI  - Formation, stability, and pH sensitivity of free-floating, giant unilamellar
      vesicles using palmitic acid-cholesterol mixtures.
AB  - Despite the fact that palmitic acid (PA) and cholesterol (Chol) do not form fluid
      bilayers once hydrated individually, giant unilamellar vesicles (GUVs) were
      formed from a mixture of palmitic acid and cholesterol, 30/70 mol/mol. These free
      floating GUVs were stable over weeks, did not aggregate and were shown to be
      highly stable in alkaline pH compared to conventional phospholipid-based GUVs.
      Acidic pH-triggered payload release from the GUVs was associated with the
      protonation state of palmitic acid that dictated the mixing lipid properties,
      thus affecting the stability of the fluid lamellar phase. The successful
      formation of PA-Chol GUVs reveals the possibility to create monoalkylated
      amphiphile-based GUVs with distinct pH stability/sensitivity. 

PMID- 25058515
TI  - The semen microbiome and its relationship with local immunology and viral load in
      HIV infection.
AB  - Semen is a major vector for HIV transmission, but the semen HIV RNA viral load
      (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced
      by genital infections and associated inflammation, but it can also occur in the
      absence of classical pathogens. Thus, we hypothesized that a dysregulated semen
      microbiome correlates with local HIV shedding. We analyzed semen samples from 49
      men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected
      men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA
      gene-based pyrosequencing and quantitative PCR. We studied the relationship of
      semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear
      regression, non-metric multidimensional scaling, and goodness-of-fit test.
      Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria,
      irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in
      HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was
      associated with decreased semen microbiome diversity and richness, which were
      restored after six months of ART. In HIV-infected men, semen bacterial load
      correlated with seven pro-inflammatory semen cytokines, including IL-6 (p =
      0.024), TNF-alpha (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was
      associated with semen VL (r(2)  = 0.18, p = 0.02). Semen bacterial load was also
      directly linked to the semen HIV VL (r(2) = 0.15, p = 0.02). HIV infection
      reshapes the relationship between semen bacteria and pro-inflammatory cytokines,
      and both are linked to semen VL, which supports a role of the semen microbiome in
      HIV sexual transmission.

PMID- 25058526
TI  - CEP-33779 antagonizes ATP-binding cassette subfamily B member 1 mediated
      multidrug resistance by inhibiting its transport function.
AB  - The overexpression of ATP-binding cassette (ABC) transporters often leads to the
      development of multidrug resistance (MDR), which is the major factor contributing
      to the failure of chemotherapy. The objective of this study was to investigate
      the enhancement of CEP-33779, a small-molecule inhibitor of Janus kinase 2
      (JAK2), on the efficacy of conventional chemotherapeutic agents in MDR cells with
      overexpression of P-glycoprotein (ABCB1), multidrug resistance-associated protein
      1 (ABCC1) and breast cancer resistance protein (ABCG2). Our results showed that
      CEP-33779, at nontoxic concentrations, significantly sensitized ABCB1
      overexpressing MDR cells to its anticancer substrates. CEP-33779 significantly
      increased intracellular accumulation and decreased the efflux of doxorubicin by
      inhibiting the ABCB1 transport function. Furthermore, CEP-33779 did not alter the
      expression of ABCB1 both at protein and mRNA levels but did stimulate the
      activity of ABCB1 ATPase. CEP-33779 was predicted to bind within the large
      hydrophobic cavity of homology modeled ABCB1. In addition, the down-regulation of
      JAK2 by shRNA altered neither the expression of ABCB1 nor the cytotoxic effect of
      chemotherapeutic agents in ABCB1-overexpressing cells. Significantly, CEP-33779
      enhanced the efficacy of vincristine against the ABCB1-overexpressing and drug
      resistant KBv200 cell xenograft in nude mice. In conclusion, we conclude that CEP
      33779 enhances the efficacy of substrate drugs in ABCB1-overexpressing cells by
      directly inhibiting ABCB1 transport function. The findings encouraged to further
      study on the combination therapy of CEP-33779 with conventional chemotherapeutic
      agents in ABCB1 mediated-MDR cancer patients. 

PMID- 25058527
TI  - AICAR induces Nrf2 activation by an AMPK-independent mechanism in hepatocarcinoma
      cells.
AB  - Hepatocellular carcinoma is one of the most frequent tumor types worldwide and
      oxidative stress represents a major risk factor in pathogenesis of liver diseases
      leading to HCC. Nuclear factor erythroid 2-related factor (Nrf2) is a
      transcription factor activated by oxidative stress that governs the expression of
      many genes which constitute the antioxidant defenses of the cell. In addition,
      oxidative stress activates AMP-activated protein kinase (AMPK), which has emerged
      in recent years as a kinase that controls the redox-state of the cell. Since both
      AMPK and Nrf2 are involved in redox homeostasis, we investigated whether there
      was a crosstalk between the both signaling systems in hepatocarcinoma cells.
      Here, we demonstrated that AMPK activator AICAR, in contrary to the A769662
      allosteric activator, induces Nrf2 activation and concomitantly modulates the
      basal redox state of the hepatocarcinoma cells. When the expression of Nrf2 is
      knocked down, AICAR failed to induce its effect on redox state. These data
      highlight a major role of Nrf2 signaling pathway in mediating the AICAR effect on
      basal oxidative state. Furthermore, we demonstrated that AICAR metabolization by
      the cell is required to induce Nrf2 activation while, the silencing of AMPK does
      not have any effect on Nrf2 activation. This suggests that AICAR-induced Nrf2
      activation is independent of AMPK activity. In conclusion, we identified AICAR as
      a potent modulator of the redox state of human hepatocarcinoma cells, via the
      Nrf2 signaling pathway and in an AMPK-independent mechanism. 

PMID- 25058528
TI  - Positively changing staffing.

PMID- 25058529
TI  - Searching for proof: Creating and using an actionable PICO question.

PMID- 25058530
TI  - Nurse peer evaluation: a roadmap to professional growth and development.

PMID- 25058532
TI  - Follow the leader: how does "followership" influence nurse burnout?

PMID- 25058533
TI  - Unit-based interventions: de-stressing the distressed.

PMID- 25058534
TI  - Revisiting the past, revamping the future: the leadership edition.

PMID- 25058535
TI  - Identifying real change leaders.

PMID- 25058536
TI  - Leadership Q&A.

PMID- 25058538
TI  - Ovarian sclerosing stromal tumour with elevated CA19-9 levels.

PMID- 25058537
TI  - Geosphere-biosphere interactions in bio-activity volcanic lakes: evidences from
      Hule and Rio Cuarto (Costa Rica).
AB  - Hule and Rio Cuarto are maar lakes located 11 and 18 km N of Poas volcano along a
      27 km long fracture zone, in the Central Volcanic Range of Costa Rica. Both lakes
      are characterized by a stable thermic and chemical stratification and recently
      they were affected by fish killing events likely related to the uprising of deep
      anoxic waters to the surface caused by rollover phenomena. The vertical profiles
      of temperature, pH, redox potential, chemical and isotopic compositions of water
      and dissolved gases, as well as prokaryotic diversity estimated by DNA
      fingerprinting and massive 16S rRNA pyrosequencing along the water column of the
      two lakes, have highlighted that different bio-geochemical processes occur in
      these meromictic lakes. Although the two lakes host different bacterial and
      archaeal phylogenetic groups, water and gas chemistry in both lakes is controlled
      by the same prokaryotic functions, especially regarding the CO2-CH4 cycle.
      Addition of hydrothermal CO2 through the bottom of the lakes plays a fundamental
      priming role in developing a stable water stratification and fuelling anoxic
      bacterial and archaeal populations. Methanogens and methane oxidizers as well as
      autotrophic and heterotrophic aerobic bacteria responsible of organic carbon
      recycling resulted to be stratified with depth and strictly related to the
      chemical-physical conditions and availability of free oxygen, affecting both the
      CO2 and CH4 chemical concentrations and their isotopic compositions along the
      water column. Hule and Rio Cuarto lakes were demonstrated to contain a CO2 (CH4,
      N2)-rich gas reservoir mainly controlled by the interactions occurring between
      geosphere and biosphere. Thus, we introduced the term of bio-activity volcanic
      lakes to distinguish these lakes, which have analogues worldwide (e.g. Kivu:
      D.R.C.-Rwanda; Albano, Monticchio and Averno: Italy; Pavin: France) from volcanic
      lakes only characterized by geogenic CO2 reservoir such as Nyos and Monoun
      (Cameroon). 

PMID- 25058540
TI  - Chemically induced Jahn-Teller ordering on manganite surfaces.
AB  - Physical and electrochemical phenomena at the surfaces of transition metal oxides
      and their coupling to local functionality remains one of the enigmas of condensed
      matter physics. Understanding the emergent physical phenomena at surfaces
      requires the capability to probe the local composition, map order parameter
      fields and establish their coupling to electronic properties. Here we demonstrate
      that measuring the sub-30-pm displacements of atoms from high-symmetry positions
      in the atomically resolved scanning tunnelling microscopy allows the physical
      order parameter fields to be visualized in real space on the single-atom level.
      Here, this local crystallographic analysis is applied to the in-situ-grown
      manganite surfaces. In particular, using direct bond-angle mapping we report
      direct observation of structural domains on manganite surfaces, and trace their
      origin to surface-chemistry-induced stabilization of ordered Jahn-Teller
      displacements. Density functional calculations provide insight into the
      intriguing interplay between the various degrees of freedom now resolved on the
      atomic level. 

PMID- 25058539
TI  - Knockdown of Drosha in human alveolar type II cells alters expression of SP-A in
      culture: a pilot study.
AB  - Human surfactant protein A (SP-A) plays an important role in surfactant
      metabolism and lung innate immunity. SP-A is synthesized and secreted by alveolar
      type II (ATII) cells, one of the two cell types of the distal lung epithelium
      (ATII and ATI). We have shown that miRNA interactions with sequence polymorphisms
      on the SP-A mRNA 3'UTRs mediate differential expression of SP-A1 and SP-A2 gene
      variants in vitro. In the present study, we describe a physiologically relevant
      model to study miRNA regulation of SP-A in human ATII. For these studies, we
      purified and cultured human ATII on an air-liquid interface matrix (A/L) or
      plastic wells without matrix (P). Gene expression analyses confirmed that cells
      cultured in A/L maintained the ATII phenotype for over 5 days, whereas P-cultured
      cells differentiated to ATI. When we transfected ATII with siRNAs to inhibit the
      expression of Drosha, a critical effector of miRNA maturation, the levels of SP-A
      mRNA and protein increased in a time dependent manner. We next characterized
      cultured ATII and ATI by studying expression of 1,066 human miRNAs using miRNA
      PCR arrays. We detected expression of >300 miRNAs with 24 miRNAs differentially
      expressed in ATII versus ATI, 12 of which predicted to bind SP-A 3'UTRs,
      indicating that these may be implicated in SP-A downregulation in ATI. Thus,
      miRNAs not only affect SP-A expression, but also may contribute to the
      maintenance of the ATII cell phenotype and/or the trans-differentiation of ATII
      to ATI cells, and may represent new molecular markers that distinguish ATII and
      ATI.

PMID- 25058541
TI  - Culture, resources, or a bit of both: increasing scholarship in family medicine.

PMID- 25058542
TI  - A mixed studies literature review of family physicians' participation in
      research.
AB  - BACKGROUND AND OBJECTIVES: Family physicians' recruitment and adherence in
      research are challenging. This mixed studies literature review sought to identify
      the extent of family physicians' participation in primary health care research,
      as well as facilitators and inhibitors of their recruitment and subsequent
      protocol adherence in research projects. METHODS: We searched Medline, Embase,
      PsycINFO, SCOPUS, Google Scholar, and BioMed Central Medical Research Methodology
      by using an explicit strategy. Sixty-two articles met predetermined selection
      criteria. Using a mixed method approach, we performed a content analysis of the
      results published in these articles to synthesize factors affecting family
      physicians' participation in research. RESULTS: Recruitment rates varied between
      2% and 81%. The most frequent types of participation requested were completion of
      questionnaires (48%) and recruitment of patients (37%). We found that family
      physicians' personal/professional factors mainly affected recruitment,
      practice/patient-related issues mainly affected adherence, and study protocol
      characteristics facilitated both recruitment and adherence of family physicians
      in research. CONCLUSIONS: This review provides a synthesis of knowledge about
      factors mediating family physicians' roles in research. Our findings offer
      material for researchers to create checklists to help create and operationalize
      protocols that respect local clinical and research realities.

PMID- 25058543
TI  - Creating a culture of inquiry in family medicine.
AB  - BACKGROUND AND OBJECTIVES: Strengthening the contribution of reflective practice
      and new knowledge generation to the learning relationships forged during graduate
      and undergraduate medical training offers a possibility to create a climate more
      conducive to the recruitment and retention of family physicians. The Culture of
      Inquiry (CI) fellowship, an immersive, experientially based training program,
      combines didactic instruction, workshops, and mentoring to develop the capacity
      of family medicine's teachers to imagine, implement, and disseminate clinically
      relevant research and stimulate collaborations with those whom they train. This
      article outlines the CI fellowship program, summarizes its outcomes, and offers
      insights about programmatic features contributing to its success. METHODS: The
      Department of Family Medicine and Community Health at Case Western Reserve
      University selected CI fellows from interested local family physicians who train
      residents and medical students. Over 10 months, with 10% effort expected from
      fellows, the CI fellowship exposed each fellow to the entire research process and
      provided technical and logistical support for the design and completion of two
      research projects. Quantitative and qualitative program evaluation were used to
      assess outcomes. RESULTS: Scholarly productivity of fellows exceeded
      expectations. Collaborations with students and residents produced a ripple effect
      that amplified the fellowship's impact by strengthening those relationships
      crucial to the creation of a culture of inquiry among family medicine's teachers,
      learners, and practitioners. CONCLUSIONS: The CI fellowship represents a highly
      replicable program to connect committed and interested clinicians to research
      mentors with the goal of increasing scholarship and creating a growing culture of
      inquiry in family medicine.

PMID- 25058544
TI  - Analysis of an interprofessional home visit assignment: student perceptions of
      team-based care, home visits, and medication-related problems.
AB  - BACKGROUND AND OBJECTIVES: Interprofessional education (IPE) is recommended by
      many as a means by which to prepare clinicians for collaborative practice and a
      mechanism by which to improve the overall quality of health care. The objective
      of this study was to determine the impact of an interprofessional medicine
      pharmacy student home visit experience on students' self-assessments of skills
      and abilities related to team-based care and identification of medication-related
      problems. METHODS: Third-year medical and fourth-year pharmacy students completed
      an interprofessional home visit centered on identification of medication-related
      problems. Students were surveyed before and after the IPE assignment to assess
      changes in self-assessed skills and abilities. Survey items consisted of Likert
      type statements on a 5-point scale (1=strongly disagree, 5=strongly agree) and
      free-text responses. Students also completed reflection papers regarding their
      experiences. RESULTS: Twenty-two medical and 20 pharmacy students conducted
      medication-focused interviews of 22 patients at home as interprofessional teams.
      Medical and pharmacy student self-assessments of skills and abilities related to
      team-based care and identification of medication-related problems improved after
      completion of the assignment. Both groups of students perceived an improvement in
      confidence regarding communication skills, both with patients and with other
      health professions students. Changes were reported on 12 survey items. Student
      feedback on the IPE experience was positive. CONCLUSIONS: Students' self
      perception of skills and abilities related to interprofessional team-based care
      and identification of medication-related problems are improved after IPE
      medication-focused home visit assignment. Student feedback supports the value of
      interprofessional patient care clinical experiences.

PMID- 25058545
TI  - Training family medicine residents in HIV primary care: a national survey of
      program directors.
AB  - BACKGROUND AND OBJECTIVES: As the number of people living with HIV steadily
      increases, severe shortages in the HIV provider workforce in the United States
      are projected. With an increased emphasis on HIV education during residency,
      family physicians could play a major role in meeting this need. METHODS: A
      nationwide survey of family medicine residency program directors (PDs) was
      conducted to determine their attitudes toward training residents in HIV care.
      RESULTS: Of 440, 224 (51%) PDs responded to the electronic survey. Teaching HIV
      care was a high priority for 20% of PDs. Twenty percent of PDs reported residents
      in their program were providing care to at least five HIV-infected patients.
      Twenty-five percent of PDs felt that their graduates had the skills to be HIV
      care providers. Fewer than 25% of PDs reported having a formal HIV curriculum or
      faculty with adequate HIV expertise. The most favored approaches to strengthen
      the HIV curriculum by PDs were: (1) a half-day mini-course (30%) and (2)
      developing a faculty member's expertise in HIV care (17%). A total of 79% of
      directors saw a need to modify their existing curriculum. CONCLUSIONS: Despite
      growing numbers of HIV-infected patients, only 25% of family medicine PDs felt
      that their graduates were adequately trained in HIV primary care, and most saw a
      need to modify their HIV curricula. Family medicine residency training programs
      have an important opportunity to develop residency curricula and increase faculty
      competence to train the next generation of clinicians in HIV care.

PMID- 25058546
TI  - Obesity bias in primary care providers.
AB  - BACKGROUND AND OBJECTIVES: At the forefront of the obesity epidemic, obesity bias
      is an under-recognized and widely prevalent barrier to optimal care of the obese
      patient, even among primary care professionals. Recommendations for the reduction
      of obesity bias include increasing provider awareness about the complex etiology
      of obesity and the difficulties obtaining sustainable weight loss. METHODS:
      Obesity bias was measured in primary care professionals (n=233) participating in
      a continuing education program, using the Anti-Fat Attitudes Questionnaire
      (AFAQ). Three sub-factors, "Fear of Fat," "Willpower," and "Dislike," were
      evaluated. Participants were divided into three primary care experience groups:
      least experienced (0--9 years, n=67), moderately experienced (10--19 years,
      n=49), and most experienced (20+ years, n=98). "Fear of Fat" and "Willpower"
      components were found to be more prevalent than "Dislike"; however, scores on the
      "Dislike" subscale were highest and significantly more prevalent in the group
      with the most experience. RESULTS: Results indicated that more experienced
      primary care professionals reported greater bias toward obese people than less
      experienced colleagues. CONCLUSIONS: Ongoing continuing education that recognizes
      the wide prevalence of obesity, encourages respect for people of size, and
      mitigates obesity stigma should be promoted for all providers, particularly those
      who have been in practice for many years.

PMID- 25058547
TI  - Performance of third-year medical students on a rural family medicine clerkship.
AB  - BACKGROUND AND OBJECTIVES: In 1999 the University of Kansas School of Medicine
      established a rural option for the required family medicine clerkship to increase
      student exposure to rural locations. The emphasis at these sites was in
      experiential learning, and students did not attend lectures. To assure that
      students who chose the rural option were receiving an equivalent educational
      experience, we compared the performance of rural students to their peers that
      received the standard clerkship experience. METHODS: We used data from family
      medicine clerkship students during 1999--2011 to compare rural students with
      those that remained on the main campus. Comparison of the groups was made with
      regard to previous academic performance and demographic data to assess for
      initial differences. While the rural students were more likely to be Caucasian,
      there was otherwise no statistical significance between the groups. We then
      compared their National Board of Medical Examiners (NBME) exam performance and
      their overall grade. RESULTS: Students who chose a rural location had a
      significantly higher clerkship grade. This was due to higher clinical
      evaluations. CONCLUSIONS: Students who completed a rural family medicine
      clerkship are not at an academic disadvantage. There are many possible
      explanations for better clinical evaluations, and a comparison of performance on
      the clinical skills assessment would be useful to determine whether the increased
      clinical experience during the rural option created a difference in clinical
      skills.

PMID- 25058548
TI  - Primary care residents want to learn about the patient-centered medical home.
AB  - BACKGROUND AND OBJECTIVES: The patient-centered medical home (PCMH) is an
      important model of primary care with a promise of improving quality, reducing
      costs, and improving patient satisfaction. Many primary care residency programs
      have PCMH initiatives, but it is unclear if residents are interested in learning
      more about the PCMH. Our objective was to examine primary care residents'
      attitudes and knowledge about the PCMH model and how it relates to them. METHODS:
      A total of 82 first- through third-year family medicine and internal medicine
      residents participated in a survey with 25 questions. Descriptive statistics were
      performed to describe the responses. RESULTS: The survey response rate was 91%.
      Sixty-one percent of residents thought they had "poor" or "fair" knowledge of the
      PCMH, and 84% thought it was important to be knowledgeable about the PCMH. Thirty
      four percent rated their ability to describe the PCMH as "well" or "very well."
      Eighty-six percent thought they learned "too little" or "way too little" about
      the PCMH during medical school. The majority (88%) of residents were interested
      in learning more about the PCMH. CONCLUSIONS: Family and internal medicine
      residents are interested in learning more about the PCMH during residency.
      Residents may benefit from experiential learning that focuses on the PCMH.

PMID- 25058549
TI  - The extent and methods of public health instruction in family medicine
      clerkships.
AB  - BACKGROUND AND OBJECTIVES: The Institute of Medicine recommends integrating
      public health (PH) and primary care to advance community health. The status of PH
      integration into family medicine clerkships (FMC) is unknown. We sought to
      determine the extent and methods of required PH instruction in FMC. METHODS: We
      used the Council of Academic Family Medicine Educational Research Alliance (CERA)
      survey of FMC directors. RESULTS: From 36%--59% of FMC directors responded to
      individual PH questions, reporting a mean of 36.3 hours (range 1--258) of PH
      instruction in the clerkship. The majority of PH instructional time relates to
      behavioral sciences, communication, and cultural competence. Forty-nine percent
      of PH instructional hours are experiential. Ninety percent of respondents agree
      that PH training is important for medical students; 67.5% of respondents agree
      that PH training is appropriate for the FMC. Respondents from public schools
      reported more PH training than respondents from private schools (43.85 +/- 9.25
      hours versus 21.29 +/- 3.82 hours). There was no difference between hours of
      instruction reported by FMC directors with shorter (? 4 weeks) and longer (> 4
      weeks) clerkships (40.8 +/- 13.7 hours versus 33.7 +/- 6.4 hours). Among
      respondents leaving comments, 24/36 (66.7%) cited insufficient time, 6/36 (16.7%)
      cited lack of funding, and others identified lack of faculty or preceptor
      expertise and lack of student interest as barriers to PH instruction.
      CONCLUSIONS: There is variability in how FMC are addressing PH instruction.
      Future research should qualitatively explore pedagogical methods and seek
      consensus on the competencies and best practices in PH instruction most suited to
      FMC.

PMID- 25058550
TI  - Compassion in medicine.

PMID- 25058551
TI  - Running away from home.

PMID- 25058552
TI  - Tear-stained sepia.

PMID- 25058553
TI  - The doctor and the violin.

PMID- 25058554
TI  - Washing dishes.

PMID- 25058555
TI  - Reading level: not the only determinant of readability.

PMID- 25058556
TI  - The role of compensating community preceptors in family medicine clerkships.

PMID- 25058557
TI  - In response. Paying community preceptors: the roles of intrinsic and extrinsic
      rewards.

PMID- 25058558
TI  - Sudden sensorineural hearing loss after laparoscopic cystectomy under general
      anaesthesia.

PMID- 25058559
TI  - Detoxification enzyme activities (CYP1A1 and GST) in the skin of humpback whales
      as a function of organochlorine burdens and migration status.
AB  - The activities of glutathione-s-transferase (GST) and cytochrome P-450 1A1
      (CYP1A1) enzymes were measured in freshly extracted epidermis of live-biopsied,
      migrating, southern hemisphere humpback whales (Megaptera novaeangliae). The two
      quantified enzyme activities did not correlate strongly with each other.
      Similarly, neither correlated strongly with any of the organochlorine compound
      groups previously measured in the superficial blubber of the sample biopsy core,
      likely reflecting the anticipated low levels of typical aryl-hydrocarbon receptor
      ligands. GST activity did not differ significantly between genders or between
      northward (early migration) or southward (late migration) migrating cohorts.
      Indeed, the inter-individual variability in GST measurements was relatively low.
      This observation raises the possibility that measured activities were basal
      activities and that GST function was inherently impacted by the fasting state of
      the sampled animals, as seen in other species. These results do not support the
      implementation of CYP1A1 or GST as effective biomarkers of organochlorine
      contaminant burdens in southern hemisphere populations of humpback whales as
      advocated for other cetacean species. Further investigation of GST activity in
      feeding versus fasting cohorts may, however, provide some insight into the
      fasting metabolism of these behaviourally adapted populations. 

PMID- 25058560
TI  - Are DNA-damaging effects induced by herbicide formulations (Roundup(r) and
      Garlon(r)) in fish transient and reversible upon cessation of exposure?
AB  - Owing to the seasonality of crop cultivation and subsequent periodic/seasonal
      application of herbicides, their input to the aquatic systems is typically
      intermittent. Consequently, exposure of fish to this type of contaminants can be
      short and followed by a period of permanence in non-contaminated areas. Thus, the
      assessment of genotoxic endpoints in fish after removal of the contamination
      source appears as a crucial step to improve the knowledge on the dynamics of
      herbicide genotoxicity, as well as to determine the actual magnitude of risk
      posed by these agrochemicals. Therefore, the present study intended to shed light
      on the ability of fish to recover from the DNA damage induced by short-term
      exposures to the herbicide formulations Roundup((r)) (glyphosate-based) and
      Garlon((r)) (triclopyr-based) upon the exposure cessation. European eel (Anguilla
      anguilla) was exposed to the above commercial formulations for 3 days, and
      allowed to recover for 1, 7 and 14 days (post-exposure period). The comet assay
      was used to identify the DNA damage in blood cells during both exposure and post
      exposure periods. As an attempt to clarify the DNA damaging mechanisms involved,
      an extra-step including the incubation of the nucleotides with DNA lesion
      specific repair enzyme was added to the standard comet. The genotoxic potential
      of both herbicides was confirmed, concerning the exposure period. In addition,
      the involvement of oxidative DNA damage on the action of Roundup((r)) (pointed
      out as pyrimidine bases oxidation) was demonstrated, while for Garlon((r)) this
      damaging mechanism was less evident. Fish exposed to Garlon((r)), though
      presenting some evidence towards a tendency of recovery, did not achieve a
      complete restoration of DNA integrity. In what concerns to Roundup((r)), a
      recovery was evident when considering non-specific DNA damage on day 14 post
      exposure. In addition, this herbicide was able to induce a late oxidative DNA
      damage (day 14). Blood cells of A. anguilla exposed to Roundup((r)) appeared to
      be more successful in repairing damage with a non-specific cause than that
      associated to base oxidation. Overall, the present findings highlighted the
      genetic hazard to fish associated to the addressed agrochemicals, reinforcing the
      hypothesis of long-lasting damage. 

PMID- 25058561
TI  - The utility of image-guided percutaneous needle aspiration biopsy for the
      diagnosis of spontaneous vertebral osteomyelitis: a systematic review and meta
      analysis.
AB  - BACKGROUND CONTEXT: Spontaneous vertebral osteomyelitis (SVOM) is mostly acquired
      via hematogenous seeding. Diagnosis of SVOM is often delayed because of the
      insidious nature and rarity of this disease. The microbiological yield of image
      guided needle biopsy varies between 36% and 91%. The utility and accuracy of this
      procedure have not been systematically reviewed. PURPOSE: To systematically
      review and assess the diagnostic accuracy of image-guided spinal biopsy for SVOM
      in adults when compared with combined reference standards. STUDY DESIGN: A
      systematic review and meta-analysis. SAMPLE: Seven retrospective studies
      involving 482 patients with clinical and/or radiologic suspicion of SVOM who
      underwent image-guided spinal biopsy were included. OUTCOME MEASURES: The primary
      outcome measure was diagnostic odds ratio (DOR). Other outcomes included
      likelihood ratio of a positive test (LRP), likelihood ratio of a negative test
      (LRN), sensitivity, and specificity. METHODS: We searched in six medical
      databases through September 1, 2013 for studies evaluating the performance of
      image-guided spinal biopsy for SVOM with no limits on language or publication
      date. Combined reference standards, which included histopathologic findings
      consistent with vertebral osteomyelitis, identifications of pathogens from open
      surgery and/or blood cultures, and/or evidence of clinical and radiologic
      improvement after empiric antimicrobial therapy, were used for comparison. The
      random-effect model was used for meta-analysis. Two reviewers independently
      selected the studies. RESULTS: Three hundred fifty-eight potentially relevant
      studies were identified. Seven studies were included in our analysis. Two studies
      that used only single reference standard were excluded in the sensitivity
      analysis, and five studies involving 352 patients were pooled. Image-guided
      spinal biopsy had a DOR of 45.50 (95% confidence interval [CI], 13.66-151.56), an
      LRP of 16.76 (95% CI, 5.51-50.95), an LRN of 0.39 (95% CI, 0.24-0.64), a
      sensitivity of 52.2% (95% CI, 45.8-58.5), and a specificity of 99.9% (95% CI,
      94.5-100). This is based on the assumption that combined reference standards are
      a valid standard for comparison. CONCLUSIONS: Image-guided spinal biopsy is
      highly specific and performs well in predicting SVOM, but has a moderate accuracy
      for ruling out this diagnosis. This procedure should be considered in the
      diagnostic work-up of adults suspected with SVOM.

PMID- 25058562
TI  - Examination of Self-Sealing Sclerotomy for Vitrectomized Eye under Gas Tamponade
      in 23-Gauge Transconjunctival Sutureless Vitrectomy.
AB  - INTRODUCTION: To investigate whether a previous history of vitrectomy affects
      sclerotomy self-sealing under gas tamponade in 23-gauge transconjunctival
      sutureless vitrectomy. MATERIALS AND METHODS: This study retrospectively reviewed
      two groups, a vitrectomized group (seven consecutive cases) and an initial
      vitrectomy group (82 consecutive cases), who underwent 23-gauge transconjunctival
      sutureless vitrectomy at Jikei University School of Medicine Daisan Hospital in
      Tokyo. Factors affecting sclerotomy self-sealing were examined using multiple
      regression analysis. The criterion variable was massage time, and independent
      variables were age, surgical time, axial length, vitreous incarceration, history
      of vitrectomy, preoperative intraocular pressure (IOP), and postoperative IOP.
      RESULTS: Age (F = 10.4) was the only significant factor. History of vitrectomy
      was not a significant factor (F = 0.06). CONCLUSIONS: Previous history of
      vitrectomy does not affect sclerotomy self-sealing under gas tamponade in 23
      gauge transconjunctival sutureless vitrectomy.

PMID- 25058563
TI  - A graphene oxide-based enzyme-free signal amplification platform for homogeneous
      DNA detection.
AB  - A graphene oxide (GO) based enzyme-free signal amplification platform for
      homogeneous DNA sensing is developed with simplicity and high sensitivity. In the
      absence of the target DNA, labeled hairpin probe 1 (H1) and probe 2 (H2) were
      adsorbed on the surface of GO, resulting in the fluorescence quenching of the
      dyes and minimizing the background fluorescence. The addition of the target DNA
      facilitated the formation of double-stranded DNA (dsDNA) between H1 and H2,
      causing the probes to separate from GO and release the target DNA through a
      strand displacement reaction. Meanwhile, the whole reaction started anew. This is
      an excellent isothermal signal amplification technique without the involvement of
      enzymes. By monitoring the change of the fluorescence intensity, the target DNA
      not only can be determined in buffer solution, but also can be detected in 1%
      serum solution spiked with a series of concentrations of the target DNA. In
      addition, the consumption amount of the probes in this method is lower than that
      in traditional molecular beacon methods. 

PMID- 25058564
TI  - Childhood adversity subtypes and depressive symptoms in early and late
      adolescence.
AB  - Within a longitudinal study of 1,005 adolescents, we investigated how exposure to
      childhood psychosocial adversities was associated with the emergence of
      depressive symptoms between 14 and 17 years of age. The cohort was classified
      into four empirically determined adversity subtypes for two age periods in
      childhood (0-5 and 6-11 years). One subtype reflects normative/optimal family
      environments (n = 692, 69%), while the other three subtypes reflect differential
      suboptimal family environments (aberrant parenting: n = 71, 7%; discordant: n =
      185, 18%; and hazardous: n = 57, 6%). Parent-rated child temperament at 14 years
      and adolescent self-reported recent negative life events in early and late
      adolescence were included in models implementing path analysis. There were gender
      differentiated associations between childhood adversity subtypes and adolescent
      depressive symptoms. The discordant and hazardous subtypes were associated with
      elevated depressive symptoms in both genders but the aberrant parenting subtype
      only so in girls. Across adolescence the associations between early childhood
      adversity and depressive symptoms diminished for boys but remained for girls.
      Emotional temperament was also associated with depressive symptoms in both
      genders, while proximal negative life events related to depressive symptoms in
      girls only. There may be neurodevelopmental factors that emerge in adolescence
      that reduce depressogenic symptoms in boys but increase such formation in girls. 

PMID- 25058565
TI  - Haptoglobin interacts with apolipoprotein E and beta-amyloid and influences their
      crosstalk.
AB  - Beta-amyloid accumulation in brain is a driving force for Alzheimer's disease
      pathogenesis. Apolipoprotein E (ApoE) represents a critical player in beta
      amyloid homeostasis, but its role in disease progression is controversial. We
      previously reported that the acute-phase protein haptoglobin binds ApoE and
      impairs its function in cholesterol homeostasis. The major aims of this study
      were to characterize the binding of haptoglobin to beta-amyloid, and to evaluate
      whether haptoglobin affects ApoE binding to beta-amyloid. Haptoglobin is here
      reported to form a complex with beta-amyloid as shown by immunoblotting
      experiments with purified proteins, or by its immunoprecipitation in brain
      tissues from patients with Alzheimer's disease. The interaction between ApoE and
      beta-amyloid was previously shown to be crucial for limiting beta-amyloid
      neurotoxicity and for promoting its clearance. We demonstrate that haptoglobin,
      rather than impairing ApoE binding to beta-amyloid, promotes to a different
      extent the formation of the complex between beta-amyloid and ApoE2 or ApoE3 or
      ApoE4. Our data suggest that haptoglobin and ApoE functions in brain should be
      evaluated taking into account their mutual interaction with beta-amyloid. Hence,
      the risk of developing Alzheimer's disease might not only be linked to the
      different ApoE isoforms, but also rely on the level of critical ligands, such as
      haptoglobin. 

PMID- 25058566
TI  - Aqueous solution synthesis of Pt-M (M = Fe, Co, Ni) bimetallic nanoparticles and
      their catalysis for the hydrolytic dehydrogenation of ammonia borane.
AB  - Platinum-based bimetallic nanocatalysts have attracted much attention due to
      their high-efficiency catalytic performance in energy-related applications such
      as fuel cell and hydrogen storage, for example, the hydrolytic dehydrogenation of
      ammonia borane (AB). In this work, a simple and green method has been
      demonstrated to successfully prepare Pt-M (M = Fe, Co, Ni) NPs with tunable
      composition (nominal Pt/M atomic ratios of 4:1, 1:1, and 1:4) in aqueous solution
      under mild conditions. All Pt-M NPs with a small size of 3-5 nm show a Pt fcc
      structure, suggesting the bimetallic formation (alloy and/or partial core-shell),
      examined by transmission electron microscopy (TEM), X-ray diffraction (XRD), and
      X-ray absorption fine structure (XAFS) analysis. The catalytic activities of Pt-M
      NPs in the hydrolytic dehydrogenation of AB reveal that Pt-Ni NPs with a ratio of
      4:1 show the best catalytic activity and even better than that of pure Pt NPs
      when normalized to Pt molar amount. The Ni oxidation state in Pt-Ni NPs has been
      suggested to be responsible for the corresponding catalytic activity for
      hydrolytic dehydrogenation of AB by XAFS study. This strategy for the synthesis
      of Pt-M NPs is simple and environmentally benign in aqueous solution with the
      potential for scale-up preparation and the in situ catalytic reaction. 

PMID- 25058567
TI  - Photopatterning of poly(N-isopropylacrylamide) membranes for a high level of
      enrichment and cleanup of nucleic acids in microfluidic chips.
AB  - An ideal nanoporous poly(N-isopropylacrylamide) membrane has been fabricated in
      glass microchannels by means of spatially controlled photopatterning technology
      for a high level of enrichment and cleanup of nucleic acids. 

PMID- 25058568
TI  - The historical development of suicide mortality in Russia, 1870-2007.
AB  - Russia has one of the highest suicide mortality rates in the world. This study
      investigates the development of Russian suicide mortality over a longer time
      period in order to provide a context within which the contemporary high level
      might be better understood. Annual sex- and age-specific suicide-mortality data
      for Russia for the period 1870-2007 were studied, where available. Russian
      suicide mortality increased 11-fold over the period. Trends in male and female
      suicide developed similarly, although male suicide rates were consistently much
      higher. From the 1990s suicide has increased in a relative sense among the young
      (15-34), while the high suicide mortality among middle-aged males has reduced.
      Changes in Russian suicide mortality over the study period may be attributable to
      modernization processes. 

PMID- 25058569
TI  - Hyalachelins A-C, unusual siderophores isolated from the terrestrial
      myxobacterium Hyalangium minutum.
AB  - Three new siderophores, termed hyalachelins A-C (1-3), were isolated from the
      terrestrial myxobacterium Hyalangium minutum. Their structures were determined by
      2D NMR and HR-MS/MS experiments, and their stereochemical configuration was
      established by a combination of NMR data, quantum mechanical calculations, and
      circular dichroism experiments. Hyalachelins are unusual catecholate-type
      siderophores that bear a 3,7,8-trihydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-3
      carboxylic acid. Their iron chelating activities were evaluated in a CAS assay
      showing EC50 values of ~30 MUM. 

PMID- 25058570
TI  - SPECT and near-infrared fluorescence imaging of breast cancer with a neuropilin-1
      targeting peptide.
AB  - Breast cancer is the most common malignant cancer and is the leading cause of
      cancer death among females. Molecular imaging is a promising approach for the
      early detection and staging of breast cancer as well as for assessing therapeutic
      responses. Tumor-targeting peptides are effective targeting vehicles for
      molecular imaging. Here, we identified a breast cancer-targeting peptide
      CLKADKAKC (CK3) contains a cryptic C-end rule motif that may mediate its binding
      to neuropilin-1 (NRP-1), an attractive therapeutic target which expression was
      associated with poor outcome of the patients with breast cancer. Phage CK3 bound
      to NRP-1-positive breast cancer cells, which could be inhibited by peptide CK3 in
      a dose-dependent manner or by knock-down NRP-1 expression. Consistently, NRP-1
      overexpression in cells increased the binding of phage CK3. Furthermore, peptide
      CK3 co-localized with NRP-1. Importantly, unlike previously reported NRP-1
      targeting peptides with exposed C-end rule motifs, peptide CK3 did not penetrate
      into lungs and heart in vivo, which could make it more clinically applicable.
      Single-photon emission CT (SPECT) and near-infrared fluorescence (NIRF) imaging
      showed enrichment of peptide CK3 to the xenograft tumors in nude mice. In
      conclusion, as a novel NRP-1-targeting peptide, peptide CK3 could be used for
      breast cancer molecular imaging, which may represent a new avenue for breast
      cancer diagnostics, staging and assessments of therapeutic response. 

PMID- 25058571
TI  - 'Stealth' lipid-based formulations: poly(ethylene glycol)-mediated digestion
      inhibition improves oral bioavailability of a model poorly water soluble drug.
AB  - For over 20years, stealth drug delivery has been synonymous with nanoparticulate
      formulations and intravenous dosing. The putative determinants of stealth in
      these applications are the molecular weight and packing density of a hydrophilic
      polymer (commonly poly(ethylene glycol) (PEG)) that forms a steric barrier at the
      surface of the nanoparticle. The current study examined the potential translation
      of the concepts learned from stealth technology after intravenous administration
      to oral drug delivery and specifically, to enhance drug exposure after
      administration of oral lipid-based formulations (LBFs) containing medium-chain
      triglycerides (MCT). MCT LBFs are rapidly digested in the gastrointestinal tract,
      typically resulting in losses in solubilisation capacity, supersaturation and
      drug precipitation. Here, non-ionic surfactants containing stealth PEG headgroups
      were incorporated into MCT LBFs in an attempt to attenuate digestion, reduce
      precipitation risk and enhance drug exposure. Stealth capabilities were assessed
      by measuring the degree of digestion inhibition that resulted from steric
      hindrance of enzyme access to the oil-water interface. Drug-loaded LBFs were
      assessed for maintenance of solubilising capacity during in vitro digestion and
      evaluated in vivo in rats. The data suggest that the structural determinants of
      stealth LBFs mirror those of parenteral formulations, i.e., the key factors are
      the molecular weight of the PEG in the surfactant headgroup and the packing
      density of the PEG chains at the interface. Interestingly, the data also show
      that the presence of labile ester bonds within a PEGylated surfactant also impact
      on the stealth properties of LBFs, with digestible surfactants requiring a PEG Mw
      of ~1800g/mol and non-digestible ether-based surfactants ~800g/mol to shield the
      lipidic cargo. In vitro evaluation of drug solubilisation during digestion showed
      stealth LBFs maintained drug solubilisation at or above 80% of drug load and
      reduced supersaturation in comparison to digestible counterparts. This trend was
      also reflected in vivo, where the relative bioavailability of drug after
      administration in two stealth LBFs increased to 120% and 182% in comparison to
      analogous digestible (non-stealth) formulations. The results of the current study
      indicate that self-assembled "stealth" LBFs have potential as a novel means of
      improving LBF performance. 

PMID- 25058572
TI  - Response to Comment on "Airborne trifluoroacetic acid and its fraction from the
      degradation of HFC-134a in Beijing, China".

PMID- 25058574
TI  - Coordination, microprotonation equilibria and conformational changes of myo
      inositol hexakisphosphate with pertinence to its biological function.
AB  - Within all the eukaryotic cells there is an important group of biomolecules that
      has been potentially related to signalling functions: the myo-inositol phosphates
      (InsPs). In nature, the most abundant member of this family is the so called
      InsP6 (phytate, L(12-)), for which our group has strived in the past to elucidate
      its intricate chemical behaviour. In this work we expand on our earlier findings,
      shedding light on the inframolecular details of its protonation and complexation
      processes. We evaluate systematically the chemical performance of InsP6 in the
      presence and absence of alkali and alkaline earth metal ions, through (31)P NMR
      measurements, in a non-interacting medium and over a wide pH range. The analysis
      of the titration curves by means of a model based on the cluster expansion method
      allows us to describe in detail the distribution of the different protonated
      microspecies of the ligand. With the aid of molecular modelling tools, we assess
      the energetic and geometrical characteristics of the protonation sequence and the
      conformational transition suffered by InsP6 as the pH changes. By completely
      characterizing the protonation pattern, conformation and geometry of the metal
      complexes, we unveil the chemical and structural basis behind the influence that
      the physiologically relevant cations, Na(+), K(+), Mg(2+) and Ca(2+) have over
      the phytate chemical reactivity. This information is essential in the process of
      gaining reliable structural knowledge about the most important InsP6 species in
      the in vitro and in vivo experiments, and how these features modulate their
      probable biological functions. 

PMID- 25058573
TI  - The incidence of Japanese encephalitis in Taiwan--a population-based study.
AB  - BACKGROUND: A mass Japanese encephalitis (JE) vaccination program targeting
      children was launched in Taiwan in 1968, and the number of pediatric JE cases
      substantially decreased thereafter. The aim of this study was to elucidate the
      long-term trend of JE incidence, and to investigate the age-specific
      seroprevalence of JE-neutralizing antibodies. METHODOLOGY/PRINCIPAL FINDINGS: A
      total of 2,948 laboratory-confirmed JE cases that occurred between 1966 and 2012
      were analyzed using a mandatory notification system managed by the Centers for
      Disease Control, Taiwan. A total of 6,594 randomly-sampled serum specimens
      obtained in a nationwide population-based survey in 2002 were analyzed to
      estimate the seroprevalence of JE-neutralizing antibodies in the general
      population. The average annual JE incidence rate of the group aged 30 years and
      older was 0.167 cases per 100,000 people between 2001 and 2012, which was higher
      than the 0.052 cases per 100,000 people among those aged under 30 years. These
      seroepidemiological findings indicate that the cohort born between 1963 and 1975,
      who generally received two or three doses of the vaccine and were administered
      the last booster dose more than 20 years ago, exhibited the lowest positive rate
      of JE-neutralizing antibodies (54%). The highest and second highest antibody
      rates were observed, respectively, in the oldest unvaccinated cohort (86%) and in
      the youngest cohort born between 1981 and 1986, who received four doses 10-15
      years ago (74%). CONCLUSION/SIGNIFICANCE: Over the past decade, the main age
      group of the confirmed JE cases in Taiwan shifted from young children to adults
      over 30 years of age. People who were born between 1963 and 1975 exhibited the
      lowest seroprevalence of JE-neutralizing antibodies. Thus, the key issue for JE
      control in Taiwan is to reduce adult JE cases through a cost-effective analysis
      of various immunization strategies.

PMID- 25058575
TI  - Molecular structure, vibrational spectroscopy, NBO and HOMO, LUMO studies of o
      methoxybenzonitrile.
AB  - In the present study, the FT-IR and FT-Raman spectra of o-methoxybenzonitrile (O
      MBN) have been recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1),
      respectively. The fundamental modes of vibrational frequencies of O-MBN are
      assigned. Theoretical information on the optimized geometry, harmonic vibrational
      frequencies, infrared and Raman intensities were obtained by means of ab initio
      Hartree-Fock (HF) and density functional theory (DFT) gradient calculations with
      complete relaxation in the potential energy surface using 6-311++G(d,p) basis
      set. The vibrational frequencies which were determined experimentally from the
      spectral data are compared with those obtained theoretically from ab initio and
      DFT calculations. A close agreement was achieved between the observed and
      calculated frequencies by refinement of the scale factors. The infrared and Raman
      spectra were also predicted from the calculated intensities. Thermodynamic
      properties like entropy, heat capacity, zero point energy, have been calculated
      for the molecule. The predicted first hyperpolarizability also shows that the
      molecule might have a reasonably good non-linear optical (NLO) behavior. The
      calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the
      molecule. Stability of the molecule arising from hyper conjugative interactions,
      charge delocalization have been analyzed using natural bond orbitals (NBO)
      analysis. Unambiguous vibrational assignment of all the fundamentals was made
      using the total energy distribution (TED).

PMID- 25058576
TI  - A new bioadhesive material from fish parasite Neobenedenia girellae.
AB  - The purpose of the work was to identify the proteins present in the adhesive
      material of the capsalid Neobenedenia girellae by a proteomic approach based on
      de novo sequencing and data base search to overcome the lack of information
      concerning the genome of these parasites. Glandular secretions were obtained by a
      new method, set up in our laboratory, which allowed collecting a small amount of
      secretion without any contamination from other tissues either from the parasites
      as well as from the skin of the host. The proteomic analysis reveals that the
      adhesive is mainly composed of cytoskeletal proteins (actin, keratin and tubulin)
      but contains also ATP-synthase, 78 kDa glucose regulated protein and albumin.
      BIOLOGICAL SIGNIFICANCE: This paper reports for the first time the
      characterization of a novel bioadhesive material used by capsalid parasites to
      adhere to fish. Such information broadens our knowledge of the molecular
      mechanisms involved in adhesiveness of parasites to hosts. Moreover, it offers
      new clues in understanding the mechanism of stickiness and adhesion of
      cytoskeleton components, often involved in both physiological and pathological
      processes, including neurodegenerative diseases.

PMID- 25058577
TI  - Comparative proteomics analysis of superior and inferior spikelets in hybrid rice
      during grain filling and response of inferior spikelets to drought stress using
      isobaric tags for relative and absolute quantification.
AB  - The biological functions of the differentially abundant proteins between superior
      and inferior spikelet grains were investigated based on the isobaric tags for
      relative and absolute quantification to further clarify the mechanism of rice
      grain filling at the proteomic level, as well as the response of inferior
      spikelets to drought dress (-20kPa or -40kPa). Compared with superior spikelets,
      inferior ones had lower sink strength due to the lower sink activities (lower
      abundances of ADP-glucose pyrophosphorylase, granule-bound starch synthase,
      starch branching enzyme and pullulanase) and smaller sink sizes (lower abundances
      of structural proteins). The slower and later grain filling resulted from the
      weaker decomposition and conversion of photoassimilate and the slower cell
      division. Moderate drought stress (-20kPa) promoted the grain filling of inferior
      spikelets through regulating the proteins associated with photoassimilate supply
      and conversion. These proteins may be important targets for rice breeding
      programs that raise the rice yield under drought condition. The findings offer
      new insights into rice grain-filling and provide theoretical evidences for better
      quality control and scientific improvement of super rice in practice. BIOLOGICAL
      SIGNIFICANCE: Rice cultivars with large panicles do not always guarantee high
      yield and grain quality probably due to the slow grain filling and many unfilled
      grains of inferior spikelets. In general, earlier-flowering superior spikelets,
      which are usually located on apical primary branches, fill faster and produce
      larger and heavier grains. In contrast, later-flowering inferior spikelets
      located on proximal secondary branches are either sterile or fill slowly and
      poorly, and the differences are more significant in large panicle rice or super
      rice. The increase of rice yield has been limited by the unsatisfactory grain
      filling of inferior spikelets, and the inferior spikelets are more prone to
      environmental factors during grain filling. Thus, we herein investigated the
      biological functions of differently abundant proteins between superior and
      inferior spikelet grains by using iTRAQ to unravel the mechanism of rice grain
      filling and the response of inferior spikelets to drought stress at proteomic
      level. This study offers new insights into rice grain-filling and provides
      valuable evidences for better quality control and scientific improvement of super
      rice in practice.

PMID- 25058578
TI  - Molecular cytogenetic characterization of multiple intrachromosomal
      rearrangements in two representatives of the genus Turdus (Turdidae,
      Passeriformes).
AB  - Turdus rufiventris and Turdus albicollis, two songbirds belonging to the family
      Turdidae (Aves, Passeriformes) were studied by C-banding, 18S rDNA, as well as
      the use of whole chromosome probes derived from Gallus gallus (GGA) and
      Leucopternis albicollis (LAL). They showed very similar karyotypes, with 2n = 78
      and the same pattern of distribution of heterochromatic blocks and hybridization
      patterns. However, the analysis of 18/28S rDNA has shown differences in the
      number of NOR-bearing chromosomes and ribosomal clusters. The hybridization
      pattern of GGA macrochromosomes was similar to the one found in songbirds studied
      by Fluorescent in situ hybridization, with fission of GGA 1 and GGA 4
      chromosomes. In contrast, LAL chromosome paintings revealed a complex pattern of
      intrachromosomal rearrangements (paracentric and pericentric inversions) on
      chromosome 2, which corresponds to GGA1q. The first inversion changed the
      chromosomal morphology and the second and third inversions changed the order of
      chromosome segments. Karyotype analysis in Turdus revealed that this genus has
      derived characteristics in relation to the putative avian ancestral karyotype,
      highlighting the importance of using new tools for analysis of chromosomal
      evolution in birds, such as the probes derived from L. albicollis, which make it
      possible to identify intrachromosomal rearrangements not visible with the use of
      GGA chromosome painting solely. 

PMID- 25058579
TI  - Interaction between workers during a short time window is required for bacterial
      symbiont transmission in Acromyrmex leaf-cutting ants.
AB  - Stable associations between partners over time are critical for the evolution of
      mutualism. Hosts employ a variety of mechanisms to maintain specificity with
      bacterial associates. Acromyrmex leaf-cutting ants farm a fungal cultivar as
      their primary nutrient source. These ants also carry a Pseudonocardia
      Actinobacteria exosymbiont on their bodies that produces antifungal compounds
      that help inhibit specialized parasites of the ants' fungal garden. Major workers
      emerge from their pupal cases (eclose) symbiont-free, but exhibit visible
      Actinobacterial coverage within 14 days post-eclosion. Using subcolony
      experiments, we investigate exosymbiont transmission within Acromyrmex colonies.
      We found successful transmission to newly eclosed major workers fostered by major
      workers with visible Actinobacteria in all cases (100% acquiring, n = 19). In
      contrast, newly eclosed major workers reared without exosymbiont-carrying major
      workers did not acquire visible Actinobacteria (0% acquiring, n = 73). We further
      show that the majority of ants exposed to major workers with exosymbionts within
      2 hours of eclosion acquired bacteria (60.7% acquiring, n = 28), while normal
      acquisition did not occur when exposure occurred later than 2 hours post-eclosion
      (0% acquiring, n = 18). Our findings show that transmission of exosymbionts to
      newly eclosed major workers occurs through interactions with exosymbiont-covered
      workers within a narrow time window after eclosion. This mode of transmission
      likely helps ensure the defensive function within colonies, as well as
      specificity and partner fidelity in the ant-bacterium association. 

PMID- 25058581
TI  - The growth and survival of Mycobacterium smegmatis is enhanced by co-metabolism
      of atmospheric H2.
AB  - The soil bacterium Mycobacterium smegmatis is able to scavenge the trace
      concentrations of H2 present in the atmosphere, but the physiological function
      and importance of this activity is not understood. We have shown that atmospheric
      H2 oxidation in this organism depends on two phylogenetically and kinetically
      distinct high-affinity hydrogenases, Hyd1 (MSMEG_2262-2263) and Hyd2 (MSMEG_2720
      2719). In this study, we explored the effect of deleting Hyd2 on cellular
      physiology by comparing the viability, energetics, transcriptomes, and
      metabolomes of wild-type vs. Deltahyd2 cells. The long-term survival of the
      Deltahyd2 mutant was significantly reduced compared to the wild-type. The mutant
      additionally grew less efficiently in a range of conditions, most notably during
      metabolism of short-chain fatty acids; there was a twofold reduction in growth
      rate and growth yield of the Deltahyd2 strain when acetate served as the sole
      carbon source. Hyd1 compensated for loss of Hyd2 when cells were grown in a high
      H2 atmosphere. Analysis of cellular parameters showed that Hyd2 was not necessary
      to generate the membrane potential, maintain intracellular pH homeostasis, or
      sustain redox balance. However, microarray analysis indicated that Deltahyd2
      cells were starved for reductant and compensated by rewiring central metabolism;
      transcripts encoding proteins responsible for oxidative decarboxylation pathways,
      the urea cycle, and ABC transporter-mediated import were significantly more
      abundant in the Deltahyd2 mutant. Metabolome profiling consistently revealed an
      increase in intracellular amino acids in the Deltahyd2 mutant. We propose that
      atmospheric H2 oxidation has two major roles in mycobacterial cells: to generate
      reductant during mixotrophic growth and to sustain the respiratory chain during
      dormancy. 

PMID- 25058582
TI  - Risk factors for adverse prognosis and death in American visceral leishmaniasis:
      a meta-analysis.
AB  - BACKGROUND: In the current context of high fatality rates associated with
      American visceral leishmaniasis (VL), the appropriate use of prognostic factors
      to identify patients at higher risk of unfavorable outcomes represents a
      potential tool for clinical practice. This systematic review brings together
      information reported in studies conducted in Latin America, on the potential
      predictors of adverse prognosis (continued evolution of the initial clinical
      conditions of the patient despite the implementation of treatment, independent of
      the occurrence of death) and death from VL. The limitations of the existing
      knowledge, the advances achieved and the approaches to be used in future research
      are presented. METHODS/PRINCIPAL FINDINGS: The full texts of 14 studies
      conforming to the inclusion criteria were analyzed and their methodological
      quality examined by means of a tool developed in the light of current research
      tools. Information regarding prognostic variables was synthesized using meta
      analysis. Variables were grouped according to the strength of evidence
      considering summary measures, patterns and heterogeneity of effect-sizes, and the
      results of multivariate analyses. The strongest predictors identified in this
      review were jaundice, thrombocytopenia, hemorrhage, HIV coinfection, diarrhea,
      age <5 and age >40-50 years, severe neutropenia, dyspnoea and bacterial
      infections. Edema and low hemoglobin concentration were also associated with
      unfavorable outcomes. The main limitation identified was the absence of
      validation procedures for the few prognostic models developed so far.
      CONCLUSIONS/SIGNIFICANCE: Integration of the results from different
      investigations conducted over the last 10 years enabled the identification of
      consistent prognostic variables that could be useful in recognizing and handling
      VL patients at higher risk of unfavorable outcomes. The development of externally
      validated prognostic models must be prioritized in future investigations.

PMID- 25058583
TI  - Proteomic landscape of the human choroid-retinal pigment epithelial complex.
AB  - IMPORTANCE: Differences in geographical protein expression in the human choroid
      retinal pigment epithelial (RPE) complex may explain molecular predisposition of
      regions to ophthalmic diseases such as age-related macular degeneration.
      OBJECTIVE: To characterize the proteome of the human choroid-RPE complex and to
      identify differentially expressed proteins in specific anatomic regions. DESIGN,
      SETTING, AND PARTICIPANTS: Experimental study of choroid-RPE tissue from 3
      nondiseased eyes. The choroid-RPE complex underwent biopsy from beneath the
      foveal, macular, and peripheral retina. Protein fractions were isolated and
      subjected to multidimensional liquid chromatography and tandem mass spectrometry.
      A bioinformatic pipeline matched peptide spectra to the human proteome, assigned
      gene ontology classification, and identified protein signaling pathways unique to
      each of the choroid-RPE regions. MAIN OUTCOMES AND MEASURES: Mean number of mass
      spectra, statistically significant differentially expressed proteins, gene
      ontology classification, and pathway representation. RESULTS: We identified a
      mean of 4403 unique proteins in each of the foveal, macular, and peripheral
      choroid-RPE tissues. Six hundred seventy-one differentially expressed proteins
      included previously known risk factors for retinal diseases related to oxidative
      stress, inflammation, and the complement cascade. Gene ontology analysis showed
      that unique categories in the foveal and macular regions included immune process
      proteins as well as protein complexes and plasma membrane proteins. The
      peripheral region contained unique antioxidant activity proteins. Many proteins
      had the highest expression in the foveal or macular regions, including
      inflammation-related proteins HLA-A, HLA-B, and HLA-C antigens; intercellular
      adhesion molecule 1 (ICAM-1); S100; transcription factor ERG; antioxidant
      superoxide dismutase 1 (SOD1); chloride intracellular channel 6 ion (CLIC6);
      activators of the complement cascade C1q, C6, and C8; and complement factor H.
      Proteins with higher expression in the periphery included bestrophin 1 (BEST1),
      transcription factor RNA binding motif protein 39 (RBM39), inflammatory mediator
      macrophage migration inhibitory factor, antioxidant SOD3, ion channel voltage
      dependent anion-selective channel protein 3 (VDAC3), and complement inhibitor
      CD55. The complement activation was among the highest represented pathways (P <
      7.5e-13). CONCLUSIONS AND RELEVANCE: This proteomic data set identifies novel
      molecular signatures in anatomically sensitive regions of the choroid-RPE
      complex. The findings give mechanistic insight into choroid-RPE function, reveal
      important choroid-RPE processes, and prioritize new pathways for therapeutic
      targeting.

PMID- 25058584
TI  - The impact of maternal cigarette smoke exposure in a rodent model on renal
      development in the offspring.
AB  - This study aimed to investigate whether maternal cigarette smoke exposure can
      disrupt fetal kidney development by changing the expression of growth and
      transcription factors essential for renal development, and thereafter predispose
      the offspring to chronic kidney disease later in life. Female Balb/c mice (6
      weeks) were exposed either to cigarette smoke or air under identical conditions,
      6 weeks prior to mating, during gestation and during lactation. Male offspring
      were sacrificed at three time points, postnatal day (P)1, P20 (weaning age), and
      13 weeks (mature age). Blood, urine, and kidneys were collected for analysis. At
      P1, the developmental genes fibroblast growth factor 2, glial cell-line derived
      neurotrophic factor and paired box 2 were upregulated at mRNA and protein levels;
      whilst fibroblast growth factor (FGF) 7 and FGF10 were downregulated. At P20,
      mRNA expression of FGF2, FGF10 and Wingless-type 4 was upregulated by maternal
      smoke exposure. These changes were normalised in adulthood. Nephron development
      was delayed, with fewer nephron numbers from P1 persisted to adulthood; while
      glomerular volume was increased at P20 but reduced in adulthood. Pro-inflammatory
      marker monocyte chemoatractant protein 1 (MCP1) was increased in the kidney by
      maternal smoke exposure. These changes were accompanied by an increased
      albumin/creatinine ratio in adulthood, suggesting reduced renal dysfunction. In
      conclusion maternal cigarette smoke exposure prior to and during pregnancy, as
      well as lactation leads to significant renal underdevelopment and functional
      abnormalities in adulthood. This study confirms the hypothesis that maternal
      smoking predisposes offspring to chronic kidney disorders. 

PMID- 25058585
TI  - Allergic contact dermatitis in psoriasis patients: typical, delayed, and non
      interacting.
AB  - Psoriasis is characterized by an apoptosis-resistant and metabolic active
      epidermis, while a hallmark for allergic contact dermatitis (ACD) is T cell
      induced keratinocyte apoptosis. Here, we induced ACD reactions in psoriasis
      patients sensitized to nickel (n = 14) to investigate underlying mechanisms of
      psoriasis and ACD simultaneously. All patients developed a clinically and
      histologically typical dermatitis upon nickel challenge even in close proximity
      to pre-existing psoriasis plaques. However, the ACD reaction was delayed as
      compared to non-psoriatic patients, with a maximum intensity after 7 days. Whole
      genome expression analysis revealed alterations in numerous pathways related to
      metabolism and proliferation in non-involved skin of psoriasis patients as
      compared to non-psoriatic individuals, indicating that even in clinically non
      involved skin of psoriasis patients molecular events opposing contact dermatitis
      may occur. Immunohistochemical comparison of ACD reactions as well as in vitro
      secretion analysis of lesional T cells showed a higher Th17 and neutrophilic
      migration as well as epidermal proliferation in psoriasis, while ACD reactions
      were dominated by cytotoxic CD8+ T cells and a Th2 signature. Based on these
      findings, we hypothesized an ACD reaction directly on top of a pre-existing
      psoriasis plaque might influence the clinical course of psoriasis. We observed a
      strong clinical inflammation with a mixed psoriasis and eczema phenotype in
      histology. Surprisingly, the initial psoriasis plaque was unaltered after self
      limitation of the ACD reaction. We conclude that sensitized psoriasis patients
      develop a typical, but delayed ACD reaction which might be relevant for patch
      test evaluation in clinical practice. Psoriasis and ACD are driven by distinct
      and independent immune mechanisms.

PMID- 25058586
TI  - Determinative developmental cell lineages are robust to cell deaths.
AB  - All forms of life are confronted with environmental and genetic perturbations,
      making phenotypic robustness an important characteristic of life. Although
      development has long been viewed as a key component of phenotypic robustness, the
      underlying mechanism is unclear. Here we report that the determinative
      developmental cell lineages of two protostomes and one deuterostome are
      structured such that the resulting cellular compositions of the organisms are
      only modestly affected by cell deaths. Several features of the cell lineages,
      including their shallowness, topology, early ontogenic appearances of rare cells,
      and non-clonality of most cell types, underlie the robustness. Simple simulations
      of cell lineage evolution demonstrate the possibility that the observed
      robustness arose as an adaptation in the face of random cell deaths in
      development. These results reveal general organizing principles of determinative
      developmental cell lineages and a conceptually new mechanism of phenotypic
      robustness, both of which have important implications for development and
      evolution. 

PMID- 25058587
TI  - Nucleot(s)ide analogues for hepatitis B virus-related hepatocellular carcinoma
      after curative treatment: a systematic review and meta-analysis.
AB  - AIM: The benefit of nucleot(s)ide analogues (NA) for hepatitis B virus (HBV)
      related hepatocellular carcinoma (HCC) after curative treatment has been widely
      debated due to the relatively weak evidence. The objective of this systematic
      review was to evaluate the effect of NA on recurrence and survival after curative
      treatment of HBV-HCC. METHODS: A systematic electronic search was performed. All
      controlled trials comparing NA versus placebo or no treatment were considered for
      inclusion. Results were expressed as Hazard Ratio for recurrence and survival
      with 95% confidence intervals using RevMan 5.2. RESULTS: We included 13 trials
      with 6350 patients. There were significant improvements for recurrence-free
      survival (HR 0.66, 95% CI 0.54-0.80; p<0.0001) and overall survival (HR 0.56, 95%
      CI 0.43-0.73; p<0.0001) in the adjuvant NA group compared with the control group.
      Sensitivity analyses confirmed the robustness of the results. There were no
      serious adverse effects being reported. Lamivudine resistance was from 28.6% to
      37.5% but could be rescued by other types of NA or combination therapy.
      CONCLUSION: Our study suggested benefits of adjuvant NA therapy following
      curative treatment of HBV-HCC. Since the great proven efficacy of NA in improving
      clinical and viral parameters besides HCC, further studies should be focused on
      broadening the indications for NA therapy after curative treatment of HBV-HCC.

PMID- 25058588
TI  - Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine
      oocyte developmental competence.
AB  - Developmental competence of in vitro matured (IVM) oocytes needs to be improved
      and this can potentially be achieved by adding recombinant bone morphogenetic
      protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of
      this study was to determine the effect of a purified pro-mature complex form of
      recombinant human BMP15 versus the commercially available bioactive forms of
      BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo
      development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were
      matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15,
      mature BMP15 or mature GDF9 +/- FSH. Metabolic measures of glucose uptake and
      lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were
      measured in oocytes after IVM. Following in vitro fertilisation and embryo
      culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium
      +/- FSH containing pro-mature BMP15 displayed significantly improved blastocyst
      development (57.7+/-3.9%, 43.5+/-4.2%) compared to controls (43.3+/-2.4%, 28.9+/
      3.7%) and to mature GDF9+FSH (36.1+/-3.0%). The mature form of BMP15 produced
      intermediate levels of blastocyst development; not significantly different to
      control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte
      NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of
      BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM
      provides a functional source of oocyte-secreted factors to improve bovine
      blastocyst development. This form of BMP15 may prove useful for improving cattle
      and human artificial reproductive technologies. 

PMID- 25058589
TI  - Correlation between EGFR amplification and the expression of microRNA-200c in
      primary glioblastoma multiforme.
AB  - Extensive infiltration of the surrounding healthy brain tissue is a critical
      feature in glioblastoma. Several miRNAs have been related to gliomagenesis, some
      of them related with the EGFR pathway. We have evaluated whole-genome miRNA
      expression profiling associated with different EGFR amplification patterns,
      studied by fluorescence in situ hybridization in tissue microarrays, of 30 cases
      of primary glioblastoma multiforme, whose clinicopathological and
      immunohistochemical features have also been analyzed. MicroRNA-200c showed a very
      significant difference between tumors having or not EGFR amplification. This
      microRNA plays an important role in epithelial-mesenchymal transition, but its
      implication in the behavior of glioblastoma is largely unknown. With respect to
      EGFR status our cases were categorized into three groups: high level EGFR
      amplification, low level EGFR amplification, and no EGFR amplification. Our
      results showed that microRNA-200c and E-cadherin expression are down-regulated,
      while ZEB1 is up-regulated, when tumors showed a high level of EGFR
      amplification. Conversely, ZEB1 mRNA expression levels were significantly lower
      in the group of tumors without EGFR amplification. Tumors with a low level of
      EGFR amplification showed ZEB1 expression levels comparable to those detected in
      the group with a high level of amplification. In this study we provide what is to
      our knowledge the first report of association between microRNA-200c and EGFR
      amplification in glioblastomas. 

PMID- 25058590
TI  - Pathogenicity of Mycobacterium tuberculosis is expressed by regulating metabolic
      thresholds of the host macrophage.
AB  - The success of Mycobacterium tuberculosis as a pathogen derives from its facile
      adaptation to the intracellular milieu of human macrophages. To explore this
      process, we asked whether adaptation also required interference with the
      metabolic machinery of the host cell. Temporal profiling of the metabolic flux,
      in cells infected with differently virulent mycobacterial strains, confirmed that
      this was indeed the case. Subsequent analysis identified the core subset of host
      reactions that were targeted. It also elucidated that the goal of regulation was
      to integrate pathways facilitating macrophage survival, with those promoting
      mycobacterial sustenance. Intriguingly, this synthesis then provided an axis
      where both host- and pathogen-derived factors converged to define determinants of
      pathogenicity. Consequently, whereas the requirement for macrophage survival
      sensitized TB susceptibility to the glycemic status of the individual, mediation
      by pathogen ensured that the virulence properties of the infecting strain also
      contributed towards the resulting pathology. 

PMID- 25058591
TI  - Reward maximization justifies the transition from sensory selection at childhood
      to sensory integration at adulthood.
AB  - In a multisensory task, human adults integrate information from different sensory
      modalities--behaviorally in an optimal Bayesian fashion--while children mostly
      rely on a single sensor modality for decision making. The reason behind this
      change of behavior over age and the process behind learning the required
      statistics for optimal integration are still unclear and have not been justified
      by the conventional Bayesian modeling. We propose an interactive multisensory
      learning framework without making any prior assumptions about the sensory models.
      In this framework, learning in every modality and in their joint space is done in
      parallel using a single-step reinforcement learning method. A simple statistical
      test on confidence intervals on the mean of reward distributions is used to
      select the most informative source of information among the individual modalities
      and the joint space. Analyses of the method and the simulation results on a
      multimodal localization task show that the learning system autonomously starts
      with sensory selection and gradually switches to sensory integration. This is
      because, relying more on modalities--i.e. selection--at early learning steps
      (childhood) is more rewarding than favoring decisions learned in the joint space
      since, smaller state-space in modalities results in faster learning in every
      individual modality. In contrast, after gaining sufficient experiences
      (adulthood), the quality of learning in the joint space matures while learning in
      modalities suffers from insufficient accuracy due to perceptual aliasing. It
      results in tighter confidence interval for the joint space and consequently
      causes a smooth shift from selection to integration. It suggests that sensory
      selection and integration are emergent behavior and both are outputs of a single
      reward maximization process; i.e. the transition is not a preprogrammed
      phenomenon.

PMID- 25058592
TI  - Propagating waves of directionality and coordination orchestrate collective cell
      migration.
AB  - The ability of cells to coordinately migrate in groups is crucial to enable them
      to travel long distances during embryonic development, wound healing and
      tumorigenesis, but the fundamental mechanisms underlying intercellular
      coordination during collective cell migration remain elusive despite considerable
      research efforts. A novel analytical framework is introduced here to explicitly
      detect and quantify cell clusters that move coordinately in a monolayer. The
      analysis combines and associates vast amount of spatiotemporal data across
      multiple experiments into transparent quantitative measures to report the
      emergence of new modes of organized behavior during collective migration of tumor
      and epithelial cells in wound healing assays. First, we discovered the emergence
      of a wave of coordinated migration propagating backward from the wound front,
      which reflects formation of clusters of coordinately migrating cells that are
      generated further away from the wound edge and disintegrate close to the
      advancing front. This wave emerges in both normal and tumor cells, and is
      amplified by Met activation with hepatocyte growth factor/scatter factor. Second,
      Met activation was found to induce coinciding waves of cellular acceleration and
      stretching, which in turn trigger the emergence of a backward propagating wave of
      directional migration with about an hour phase lag. Assessments of the relations
      between the waves revealed that amplified coordinated migration is associated
      with the emergence of directional migration. Taken together, our data and
      simplified modeling-based assessments suggest that increased velocity leads to
      enhanced coordination: higher motility arises due to acceleration and stretching
      that seems to increase directionality by temporarily diminishing the velocity
      components orthogonal to the direction defined by the monolayer geometry. Spatial
      and temporal accumulation of directionality thus defines coordination. The
      findings offer new insight and suggest a basic cellular mechanism for long-term
      cell guidance and intercellular communication during collective cell migration. 

PMID- 25058593
TI  - Comparative characterization of mAb producing hapten-specific hybridoma cells by
      flow cytometric analysis and ELISA.
AB  - A novel method that optimizes the screening for antibody-secreting hapten
      specific hybridoma cells by using flow cytometry is described. Cell clones
      specific for five different haptens were analyzed. We selectively double stained
      and analyzed fixed hybridoma cells with fluorophore-labeled haptens to
      demonstrate the target-selectivity, and with a fluorophore-labeled anti-mouse IgG
      antibody to characterize the level of surface expression of membrane-bound IgGs.
      ELISA measurements with the supernatants of the individual hybridoma clones
      revealed that antibodies from those cells, which showed the highest fluorescence
      intensities in the flow cytometric analysis, also displayed the highest
      affinities for the target antigens. The fluorescence intensity of antibody
      producing cells corresponded well with the produced antibodies' affinities toward
      their respective antigens. Immunohistochemical staining verified the successful
      double labeling of the cells. Our method makes it possible to perform a high
      throughput screening for hybridoma cells, which have both an adequate IgG
      production rate and a high target affinity. 

PMID- 25058594
TI  - An unusual cause of hemifacial spasm.
AB  - Hemifacial spasm is not an infrequent presentation and a vascular loop is
      commonly implicated. Cerebellopontine angle (CPA) lesions are uncommon but can be
      excluded with appropriate imaging. There have been only around 150 case reports
      of CPA lipoma; hemifacial spasm has been associated only in eight cases. We
      present an additional case and discuss the literature and management.

PMID- 25058595
TI  - The expanded diversity of methylophilaceae from Lake Washington through
      cultivation and genomic sequencing of novel ecotypes.
AB  - We describe five novel Methylophilaceae ecotypes from a single ecological niche
      in Lake Washington, USA, and compare them to three previously described ecotypes,
      in terms of their phenotype and genome sequence divergence. Two of the ecotypes
      appear to represent novel genera within the Methylophilaceae. Genome-based
      metabolic reconstruction highlights metabolic versatility of Methylophilaceae
      with respect to methylotrophy and nitrogen metabolism, different ecotypes
      possessing different combinations of primary substrate oxidation systems (MxaFI
      type methanol dehydrogenase versus XoxF-type methanol dehydrogenase; methylamine
      dehydrogenase versus N-methylglutamate pathway) and different potentials for
      denitrification (assimilatory versus respiratory nitrate reduction). By comparing
      pairs of closely related genomes, we uncover that site-specific recombination is
      the main means of genomic evolution and strain divergence, including lateral
      transfers of genes from both closely- and distantly related taxa. The new
      ecotypes and the new genomes contribute significantly to our understanding of the
      extent of genomic and metabolic diversity among organisms of the same family
      inhabiting the same ecological niche. These organisms also provide novel
      experimental models for studying the complexity and the function of the microbial
      communities active in methylotrophy. 

PMID- 25058596
TI  - Predicting physical stability in pressurized metered dose inhalers via dwell and
      instantaneous force colloidal probe microscopy.
AB  - Colloidal probe microscopy (CPM) is a quantitative predictive tool, which can
      offer insight into particle behavior in suspension pressurized metered dose
      inhalers (pMDIs). Although CPM instantaneous force measurements, which involve
      immediate retraction of the probe upon sample contact, can provide information on
      inter-particle attractive forces, they lack the ability to appropriately imitate
      all critical particle pMDI interactions (e.g., particle re-dispersion after
      prolonged pMDI storage). In this paper, two novel dwell force techniques -
      indentation and deflection dwell - were employed to mimic long-term particle
      interactions present in pMDIs, using particles of various internal structures and
      a model liquid propellant (2H,3H perfluoropentane) as a model system. Dwell
      measurements involve particle contact for an extended period of time. In
      deflection dwell mode the probe is held at a specific position, while in
      indentation dwell mode the probe is forced into the sample with a constant force
      for the entirety of the contact time. To evaluate the applicability of CPM to
      predict actual pMDI physical stability, inter-particle force measurements were
      compared with qualitative and quantitative bulk pMDI measurement techniques
      (visual quality and light scattering). Measured instantaneous attractive (snap
      in) and adhesive (max-pull) forces decreased as a function of increasing surface
      area, while adhesive forces measured by indentation dwell decreased as a function
      of dwell contact time for particles containing voids. Instantaneous force
      measurements provided information on the likelihood of floccule formation, which
      was predictive of partitioning rates, while indentation dwell force measurements
      were predictive of formulation re-dispersibility after prolonged storage. Dwell
      force measurements provide additional information on particle behavior within a
      pMDI not obtainable via instantaneous measurements. 

PMID- 25058597
TI  - Heavy metals induce oxidative stress and trigger oxidative stress-mediated heat
      shock protein (hsp) modulation in the intertidal copepod Tigriopus japonicus.
AB  - Heat shock proteins (hsps) are induced by a wide range of environmental stressors
      including heavy metals in aquatic organisms. However, the effect of heavy metals
      on zooplankton at the molecular level remains still unclear. In this study, we
      measured the intracellular reactive oxygen species (ROS) level and the
      antioxidant enzyme activities for 96 h after exposure to five heavy metals:
      arsenic (As), cadmium (Cd), copper (Cu), silver (Ag), and zinc (Zn) in the
      intertidal copepod Tigriopus japonicus. Activities of the antioxidant enzymes
      were highly elevated in metal-exposed copepods, indicating that heavy metals can
      induce oxidative stress by generating ROS, and stimulate the involvement of
      antioxidant enzymes as cellular defense mechanisms. Subsequently, transcriptional
      changes in hsp gene families were further investigated in the metal-exposed
      groups for 96 h. The ROS level and glutathione (GSH) content were significantly
      increased in Ag-, As-, and Cu-exposed copepods, while they were only slightly
      elevated in Cd- and Zn-exposed groups. Based on the numbers of significantly
      modulated hsp genes and their expression levels for 96 h, we measured the effect
      of heavy metals to stress genes of T. japonicus in the following order: Cu > Zn >
      Ag > As > Cd, implying that Cu acts as a stronger oxidative stress inducer than
      other heavy metals. Of them, the expression of hsp20 and hsp70 genes was
      substantially modulated by exposure to heavy metals, indicating that these genes
      would provide a sensitive molecular biomarker for aquatic monitoring of heavy
      metal pollution.

PMID- 25058598
TI  - Diffusion sampler for compound specific carbon isotope analysis of dissolved
      hydrocarbon contaminants.
AB  - Compound Specific Isotope Analysis (CSIA) is widely utilized to study the fate of
      organic contaminants in groundwater. To date, however, no method is available to
      obtain CSIA samples at a fine (cm) spatial scale across the sediment-surface
      water interface (SWI), a key boundary for discharge of contaminated groundwater
      to surface water. Dissolved contaminants in such discharged zones undergo rapid
      temporal and spatial changes due to heterogeneity in redox conditions and
      microbial populations. The compatibility of a passive sediment pore water sampler
      ("peeper") to collect 40 mL samples for CSIA of benzene, toluene,
      monochlorobenzene, and 1,2-dichlorobenzene at field-relevant concentrations (0.1
      5 mg L(-1)) was evaluated in laboratory experiments. Results demonstrate that
      physical diffusion across the polysulfone membrane does not alter the carbon
      isotope values (+/-0.50/00). Measured delta(13)C values also remain invariant
      despite significant adsorption of the compounds on the peeper material, an effect
      which increased with higher numbers of chlorine atoms and sorption coefficient
      (Koc) values. In addition, isotope equilibrium between the peeper chamber and the
      sediment pore water occurred in less than a day, indicating the peeper method can
      be used to provide samples for CSIA analysis at fine spatial and temporal
      sampling resolutions in contaminated sediments. 

PMID- 25058599
TI  - Gene expression profile analysis for different idiopathic interstitial pneumonias
      subtypes.
AB  - OBJECTIVE: Idiopathic interstitial pneumonias (IIPs) are a group of diffuse
      parenchymal lung diseases of unknown etiology characterized by the presence of
      various degrees of inflammation and fibrosis. We aimed to screen the differences
      among IIPs subtypes in the gene level by using the microarray expression profiles
      of normal lung tissue and IIPs tissue for the key genes associated with early
      diagnosis and treatment of IIPs. METHODS: The gene expression profile of six
      kinds of IIPs (GSE 32537) subtypes tissue and normal lung tissues were
      downloaded. The differentially expressed genes (DEGs) in different IIPs subtypes
      were selected by using the expression profiling. In addition, the screened DEGs
      were further analyzed by function annotation, pathway analysis, and interaction
      network analysis to reveal the differences among these subtypes. RESULTS: The
      gene expression analysis showed that nine genes including SERPINA3, IL1R2, CBS,
      MGAM, SLCO4A1, S100A12, FPR1, SDR16C5, and MT1X in six subtypes of IIPs were
      significantly increased. There were significant differences in DEGs among six
      subtypes of IIPs, and the DEGs of some IIPs subtypes involved in immune,
      inflammatory response and cell adhesion processes. Moreover, the PPI network
      analysis indicated that SERPINA3 played an important role in the molecular
      mechanisms of IIPs. CONCLUSION: This comprehensive description of altered gene
      expression in different subtypes of IIPs underscores the complex biological
      processes characteristic of different subtypes of IIPs and may provide a
      foundation for future research into this devastating disease.

PMID- 25058600
TI  - ErbB4, a receptor tyrosine kinase, coordinates organization of the seminiferous
      tubules in the developing testis.
AB  - Although close to every fifth couple nowadays has difficulty conceiving, the
      molecular mechanisms behind the decline in human reproduction remain poorly
      understood. We report here that the receptor tyrosine kinase Erbb4 is a candidate
      causal gene, because it is expressed in a sexually dimorphic manner and is
      abundant in the developing and adult testes in the mouse. Sertoli cell-specific
      Erbb4-knockout mice have a compromised 3-dimensional organization of the
      testicular seminiferous tubules that affects their fertility. More specifically,
      adhesion defects are observed in the absence of Erbb4, which are characterized by
      changes in the expression of laminin-1, N-cadherin, claudin-3, and certain cell
      cell junction components between the Sertoli and germ cells. Interestingly, Erbb4
      knockout also had an effect on the Leydig cells, which suggests a paracrine
      influence of Sertoli cells expressing ErbB4. Many of the defects observed in
      Erbb4-knockout mice are rescued in targeted ERBB4 gain-of-function mice, pointing
      to a coordination role for ErbB4 in the developing testis. Thus, the ErbB4
      receptor tyrosine kinase promotes seminiferous tubule development by controlling
      Sertoli cell and germ cell adhesion. 

PMID- 25058601
TI  - Aging impairs VEGF-mediated, androgen-dependent regulation of angiogenesis.
AB  - There is a progressive impairment of vascular repair mechanisms with advancing
      age concomitant with a steady decline in circulating androgen levels in men.
      Emerging evidence indicates androgens regulate angiogenesis; however, little
      research has focused on the impact of age upon androgen-mediated regulation of
      angiogenic mechanisms. Human dermal fibroblasts from young (<30 years) and older
      (>65 years) men were incubated with DHT, with or without androgen receptor
      antagonist hydroxyflutamide, or phosphoinositide 3-kinase inhibitor. Fibroblast
      conditioned medium was used to stimulate angiogenic functions in human umbilical
      vein endothelial cells. Nuclear fractionation and fluorescence microscopy were
      used to study androgen receptor (AR) distribution. Conditioned medium from
      fibroblasts of young men, but not old men, treated with DHT produced a 3-fold
      increase in human umbilical vein endothelial cell tubulogenesis and 2-fold
      increase in migration via increased vascular endothelial growth factor (VEGF)
      expression and secretion, predominantly of VEGF145. DHT-induced VEGF secretion
      from fibroblasts of young men was AR-dependent and increased AKT phosphorylation,
      which was abrogated by phosphoinositide 3-kinase inhibition. By contrast,
      fibroblasts from older men were unresponsive to DHT and lacked androgen-mediated
      enhancement in VEGF production. These findings were associated with reduced AR
      nuclear translocation in old fibroblasts. The failure of DHT-induced paracrine
      stimulation of angiogenesis in fibroblasts from older men is likely due to
      defective nuclear translocation of AR. This first demonstration of androgen
      resistance (or insensitivity) acquired by human fibroblasts with aging suggests
      that pharmacological testosterone therapy for old men may be less effective in
      enhancing angiogenesis and facilitating tissue regeneration mechanisms reliant on
      paracrine release of VEGF. 

PMID- 25058602
TI  - Fatty acid synthesis and oxidation in cumulus cells support oocyte maturation in
      bovine.
AB  - Oocyte meiotic maturation requires energy from various substrates including
      glucose, amino acids, and lipids. Mitochondrial fatty acid (FA) beta-oxidation
      (FAO) in the oocyte is required for meiotic maturation, which is accompanied by
      differential expression of numerous genes involved in FAs metabolism in
      surrounding cumulus cells (CCs) in vivo. The objective was to elucidate
      components involved in FAs metabolism in CCs during oocyte maturation. Twenty
      seven genes related to lipogenesis, lipolysis, FA transport, and FAO were chosen
      from comparative transcriptome analysis of bovine CCs before and after maturation
      in vivo. Using real-time PCR, 22 were significantly upregulated at different
      times of in vitro maturation (IVM) in relation to oocyte meiosis progression from
      germinal vesicle breakdown to metaphase-II. Proteins FA synthase, acetyl-coenzyme
      A carboxylase, carnitine palmitoyltransferase, perilipin 2, and FA binding
      protein 3 were detected by Western blot and immunolocalized to CCs and oocyte
      cytoplasm, with FA binding protein 3 concentrated around oocyte chromatin. By
      mass spectrometry, CCs lipid profiling was shown to be different before and after
      IVM. FAO inhibitors etomoxir and mildronate dose-dependently decreased the oocyte
      maturation rate in vitro. In terms of viability, cumulus enclosed oocytes were
      more sensitive to etomoxir than denuded oocytes. In CCs, etomoxir (150 MUM) led
      to downregulation of lipogenesis genes and upregulated lipolysis and FAO genes.
      Moreover, the number of lipid droplets decreased, whereas several lipid species
      were more abundant compared with nontreated CCs after IVM. In conclusion, FAs
      metabolism in CCs is important to maintain metabolic homeostasis and may
      influence meiosis progression and survival of enclosed oocytes.

PMID- 25058603
TI  - Differential transcriptional and posttranslational transcription factor 7-like
      regulation among nondiabetic individuals and type 2 diabetic patients.
AB  - Human genetic studies have revealed that the T minor allele of single nucleotide
      polymorphism rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene is
      strongly associated with an increased risk of diabetes by 30%-40%. Molecular and
      clinical studies are of great importance for understanding how this unique
      variation in TCF7L2 influences type 2 diabetes (T2D) onset and progression. At
      the molecular level, some studies have been performed in diabetic mice and
      pancreatic islets from healthy human donors. Whereas TCF7L2 mRNA levels are up
      regulated in islets, protein levels are down-regulated. We performed studies on
      TCF7L2 splicing, mRNA expression, and protein levels in immortalized human
      lymphocytes from nondiabetic individuals and T2D patients carrying the C/C or the
      at-risk T/T genotype. Our results show differential expression of TCF7L2 splice
      variants between nondiabetic and T2D patients carrying the at-risk genotype, as
      well as differences in protein levels. Therefore, we investigated the regulation
      of splice variants, and our results propose that splicing of exon 4 is under
      control of the serine-arginine-rich factor transformer 2 beta (TRA2B). Finally,
      we studied the endoplasmic reticulum stress pathways, looking for a
      posttranslational explanation. We saw a shift in the activation of these pathways
      between nondiabetic individuals and T2D patients carrying the at-risk genotype.
      These results suggest that, in human immortalized lymphocytes carrying the at
      risk T/T genotype, first the differential expression of TCF7L2 splice variants
      implies a regulation, at least for exon 4, by TRA2B and second, the differential
      protein levels between both T/T carriers point to a different activation of
      endoplasmic reticulum stress pathways. 

PMID- 25058604
TI  - Correlation between depth perception by three-rods test and stereoacuity by
      distance Randot Stereotest.
AB  - BACKGROUND: The examination of depth perception with three-rods test, in addition
      to visual acuity testing, is required to obtain motor vehicle license to drive
      taxies and trucks, according to the Road Traffic Act in Japan. The aim of this
      study was to examine whether the results of the three-rods test would correlate
      with the results of static stereopsis tests, used in ophthalmic practice.
      METHODS: This study involved 54 normal subjects, 9 women and 45 men, with ages
      ranging from 18 to 25 (mean, 20.8) years. All had visual acuity of 0.8 or better
      with or without glasses or contact lenses correction and had no strabismus at the
      distant (5 m) or near (0.3 m) fixation. TNO Stereotest and Titmus Stereotest were
      examined at 40 cm while Distance Randot Stereotest was at 3 m. At three-rods
      test, a central rod was moved at the speed of 50 mm/sec forward and backward
      automatically against two laterally located fixed rods, placed inside the
      illuminated box. An examinee at the distance of 2.5 m observed the rods inside
      the box from a small viewing window and pushed a button to stop the central rod
      in alignment with the fixed rods. Erred distance (mm) of the central rod from the
      fixed rods as a mean of 4 measurements was correlated with stereoacuity in second
      of arc, measured by three kinds of the stereopsis tests. RESULTS: The erred
      distance of three-rods test was positively correlated with static stereoacuity at
      distance measured with Distance Randot Stereotest (rho=0.418, p=0.0023, Spearman
      rank correlation test) and also with the other stereopsis tests at near fixation.
      The stereoacuity at near fixation, measured by TNO Stereotest and Titmus
      Stereotest, was positively correlated with each other (rho=0.431, p=0.0017).
      CONCLUSION: Three-rods test, examining depth perception, together with the
      response by eye-hand coordination, gave consistent results with distant static
      stereoacuity when measured with Distance Randot Stereotest.

PMID- 25058605
TI  - Forelimb amputation-induced reorganization in the ventral posterior lateral
      nucleus (VPL) provides a substrate for large-scale cortical reorganization in rat
      forepaw barrel subfield (FBS).
AB  - In this study, we examined the role of the ventral posterior lateral nucleus
      (VPL) as a possible substrate for large-scale cortical reorganization in the
      forepaw barrel subfield (FBS) of primary somatosensory cortex (SI) that follows
      forelimb amputation. Previously, we reported that, 6 weeks after forelimb
      amputation in young adult rats, new input from the shoulder becomes expressed
      throughout the FBS that quite likely has a subcortical origin. Subsequent
      examination of the cuneate nucleus (CN) 1 to 30 weeks following forelimb
      amputation showed that CN played an insignificant role in cortical reorganization
      and led to the present investigation of VPL. As a first step, we used
      electrophysiological recordings in forelimb intact adult rats (n=8) to map the
      body representation in VPL with particular emphasis on the forepaw and shoulder
      representations and showed that VPL was somatotopically organized. We next used
      stimulation and recording techniques in forelimb intact rats (n=5) and examined
      the pattern of projection (a) from the forelimb and shoulder to SI, (b) from the
      forepaw and shoulder to VPL, and (c) from sites in the forepaw and shoulder
      representation in VPL to forelimb and shoulder sites in SI. The results showed
      that the projections were narrowly focused and homotopic. Electrophysiological
      recordings were then used to map the former forepaw representation in forelimb
      amputated young adult rats (n=5) at 7 to 24 weeks after amputation. At each time
      period, new input from the shoulder was observed in the deafferented forepaw
      region in VPL. To determine whether the new shoulder input in the deafferented
      forepaw VPL projected to a new shoulder site in the deafferented FBS, we examined
      the thalamocortical pathway in 2 forelimb-amputated rats. Stimulation of a new
      shoulder site in deafferented FBS antidromically-activated a cell in the former
      forepaw territory in VPL; however, similar stimulation from a site in the
      original shoulder representation, outside the deafferented region, in SI did not
      activate cells in the former forepaw VPL. These results suggest that the new
      shoulder input in deafferented FBS is relayed from cells in the former forepaw
      region in VPL. In the last step, we used anatomical tracing and stimulation and
      recording techniques in forelimb intact rats (n=9) to examine the cuneothalamic
      pathway from shoulder and forepaw receptive field zones in CN to determine
      whether projections from the shoulder zone might provide a possible source of
      shoulder input to forepaw VPL. Injection of biotinylated dextran amine (BDA) into
      physiologically identified shoulder responsive sites in CN densely labeled axon
      terminals in the shoulder representation in VPL, but also gave off small
      collateral branches into forepaw VPL. In addition, microstimulation delivered to
      forepaw VPL antidromically-activated cells in shoulder receptive field sites in
      CN. These results suggest that forepaw VPL also receives input from shoulder
      receptive sites in CN that are latent or subthreshold in forelimb intact rats.
      However, we speculate that following amputation these latent shoulder inputs
      become expressed, possibly as a down-regulation of GABA inhibition from the
      reticular nucleus (RTN). These results, taken together, suggest that VPL provides
      a substrate for large-scale cortical reorganization that follows forelimb
      amputation. 

PMID- 25058606
TI  - Cytokine profiles in clinical subtypes of ophthalmic Graves' disease.
AB  - PURPOSE: To examine the association of cytokines in the two clinical subtypes of
      ophthalmic Graves' disease by comparing cytokine expression in the fat and
      ethmoid tissue of type I and type II patients. METHODS: Patients needing orbital
      decompression or eyelid surgery were identified and enrolled into a prospective
      study. Patients were assigned to the type I or type II subclassification, based
      on the presence of diplopia. Orbital fat, sinus tissue or muscle removed during
      surgery was evaluated. The mRNA expression profiles of Th1 cytokines (TNF
      alpha/beta, IFN-gamma, IL-2) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were
      analyzed using real time PCR. RESULTS: 30 patients were enrolled in the study: 5
      type I (80% female), 14 type II (71% female) and 11 controls (73% female). There
      were 14 decompressions (3 type I and 11 type II), 17 lid procedures (2 type I, 4
      type II and 11 controls) and 10 ethmoidectomies (3 type I and 7 type II). The
      average ages were 45, 56 and 66 in the type I, type II and control groups,
      respectively. There was more TNF-alpha (p value 0.009) and IL-6 (p value 0.04) in
      ethmoid sinus cells of type II patients compared to ethmoid sinus cells of type I
      patients and a trend of higher expression of all cytokines in type II patients.
      CONCLUSIONS: There is a trend towards greater mRNA expression of both Th1 and Th2
      cytokines in both orbital fat and ethmoidal sinus tissue of type II patients
      compared to type I patients.

PMID- 25058607
TI  - Long-term positive and negative psychological late effects for parents of
      childhood cancer survivors: a systematic review.
AB  - Increasing survival rates in childhood cancer have yielded a growing population
      of parents of childhood cancer survivors (CCSs). This systematic review compiles
      the literature on positive and negative long-term psychological late effects for
      parents of CCSs, reported at least five years after the child's diagnosis and/or
      two years after the end of the child's treatment. Systematic searches were made
      in the databases CINAHL, EMBASE, PsycINFO, and PubMed. Fifteen studies, published
      between 1988 and 2010, from 12 projects were included. Thirteen studies used
      quantitative methodology, one quantitative and qualitative methodology, and one
      qualitative methodology. A total of 1045 parents participated in the reviewed
      studies. Mean scores were within normal ranges for general psychological
      distress, coping, and family functioning. However, a substantial subgroup
      reported a clinical level of general psychological distress, and 21-44% reported
      a severe level of posttraumatic stress symptoms. Worry, disease-related thoughts
      and feelings, marital strains, as well as posttraumatic growth was reported.
      Several factors were associated with the long-term late effects, such as parents'
      maladaptive coping during earlier stages of the childs disease trajectory and
      children's current poor adjustment. Quality assessments of reviewed studies and
      clinical implications of findings are discussed and recommendations for future
      research are presented. 

PMID- 25058608
TI  - Ocular pentastomiasis in the Democratic Republic of the Congo.
AB  - Ocular pentastomiasis is a rare infection caused by the larval stage of
      pentastomids, an unusual group of crustacean-related parasites. Zoonotic
      pentastomids have a distinct geographical distribution and utilize reptiles or
      canids as final hosts. Recently, an increasing number of human abdominal
      infections have been reported in Africa, where pentastomiasis is an emerging,
      though severely neglected, tropical disease. Here we describe four ocular
      infections caused by pentastomids from the Democratic Republic of the Congo. Two
      cases underwent surgery and an Armillifer grandis infection was detected by
      morphological and molecular approaches. Thus far, 15 other cases of ocular
      pentastomiasis have been reported worldwide. Twelve cases were caused by
      Armillifer sp., recorded almost exclusively in Africa, where such infections
      occur as a consequence of hunting and consuming snakes, their final hosts. Seven
      further cases were caused by Linguatula serrata, a cosmopolitan pentastomid whose
      final hosts are usually canids. Intraocular infections caused permanent visual
      damage in 69% and a total loss of vision in 31% of reported cases. In contrast,
      ocular adnexal cases had a benign clinical course. Further research is required
      to estimate the burden, therapeutic options and pathogenesis of this neglected
      disease. 

PMID- 25058609
TI  - Gluco-incretins regulate beta-cell glucose competence by epigenetic silencing of
      Fxyd3 expression.
AB  - BACKGROUND/AIMS: Gluco-incretin hormones increase the glucose competence of
      pancreatic beta-cells by incompletely characterized mechanisms. METHODS: We
      searched for genes that were differentially expressed in islets from control and
      Glp1r-/-; Gipr-/- (dKO) mice, which show reduced glucose competence.
      Overexpression and knockdown studies; insulin secretion analysis; analysis of
      gene expression in islets from control and diabetic mice and humans as well as
      gene methylation and transcriptional analysis were performed. RESULTS: Fxyd3 was
      the most up-regulated gene in glucose incompetent islets from dKO mice. When
      overexpressed in beta-cells Fxyd3 reduced glucose-induced insulin secretion by
      acting downstream of plasma membrane depolarization and Ca++ influx. Fxyd3
      expression was not acutely regulated by cAMP raising agents in either control or
      dKO adult islets. Instead, expression of Fxyd3 was controlled by methylation of
      CpGs present in its proximal promoter region. Increased promoter methylation
      reduced Fxyd3 transcription as assessed by lower abundance of H3K4me3 at the
      transcriptional start site and in transcription reporter assays. This epigenetic
      imprinting was initiated perinatally and fully established in adult islets.
      Glucose incompetent islets from diabetic mice and humans showed increased
      expression of Fxyd3 and reduced promoter methylation. CONCLUSIONS/INTERPRETATION:
      Because gluco-incretin secretion depends on feeding the epigenetic regulation of
      Fxyd3 expression may link nutrition in early life to establishment of adult beta
      cell glucose competence; this epigenetic control is, however, lost in diabetes
      possibly as a result of gluco-incretin resistance and/or de-differentiation of
      beta-cells that are associated with the development of type 2 diabetes.

PMID- 25058610
TI  - Microbial diversity of a Mediterranean soil and its changes after biotransformed
      dry olive residue amendment.
AB  - The Mediterranean basin has been identified as a biodiversity hotspot, about
      whose soil microbial diversity little is known. Intensive land use and aggressive
      management practices are degrading the soil, with a consequent loss of fertility.
      The use of organic amendments such as dry olive residue (DOR), a waste produced
      by a two-phase olive-oil extraction system, has been proposed as an effective way
      to improve soil properties. However, before its application to soil, DOR needs a
      pre-treatment, such as by a ligninolytic fungal transformation, e.g. Coriolopsis
      floccosa. The present study aimed to describe the bacterial and fungal diversity
      in a Mediterranean soil and to assess the impact of raw DOR (DOR) and C. floccosa
      transformed DOR (CORDOR) on function and phylogeny of soil microbial communities
      after 0, 30 and 60 days. Pyrosequencing of the 16S rRNA gene demonstrated that
      bacterial diversity was dominated by the phyla Proteobacteria, Acidobacteria, and
      Actinobacteria, while 28S-rRNA gene data revealed that Ascomycota and
      Basidiomycota accounted for the majority of phyla in the fungal community. A
      Biolog EcoPlate experiment showed that DOR and CORDOR amendments decreased
      functional diversity and altered microbial functional structures. These changes
      in soil functionality occurred in parallel with those in phylogenetic bacterial
      and fungal community structures. Some bacterial and fungal groups increased while
      others decreased depending on the relative abundance of beneficial and toxic
      substances incorporated with each amendment. In general, DOR was observed to be
      more disruptive than CORDOR. 

PMID- 25058611
TI  - MALDI-TOF mass spectrometry detection of pathogens in vectors: the Borrelia
      crocidurae/Ornithodoros sonrai paradigm.
AB  - BACKGROUND: In Africa, relapsing fever borreliae are neglected vector-borne
      pathogens that cause mild to deadly septicemia and miscarriage. Screening vectors
      for the presence of borreliae currently requires technically demanding, time- and
      resource-consuming molecular methods. Matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS) has recently emerged as a tool
      for the rapid identification of vectors and the identification of cultured
      borreliae. We investigated whether MALDI-TOF-MS could detect relapsing fever
      borreliae directly in ticks. METHODOLOGY/PRINCIPAL FINDINGS: As a first step, a
      Borrelia MALDI-TOF-MS database was created to house the newly determined Mean
      Spectrum Projections for four Lyme disease group and ten relapsing fever group
      reference borreliae. MALDI-TOF-MS yielded a unique protein profile for each of
      the 14 tested Borrelia species, with 100% reproducibility over 12 repeats. In a
      second proof-of-concept step, the Borrelia database and a custom software program
      that subtracts the uninfected O. sonrai profile were used to detect Borrelia
      crocidurae in 20 Ornithodoros sonrai ticks, including eight ticks that tested
      positive for B. crocidurae by PCR-sequencing. A B. crocidurae-specific pattern
      consisting of 3405, 5071, 5898, 7041, 8580 and 9757-m/z peaks was found in all B.
      crocidurae-infected ticks and not found in any of the un-infected ticks. In a
      final blind validation step, MALDI-TOF-MS exhibited 88.9% sensitivity and 93.75%
      specificity for the detection of B. crocidurae in 50 O. sonrai ticks, including
      18 that tested positive for B. crocidurae by PCR-sequencing. MALDI-TOF-MS took 45
      minutes to be completed. CONCLUSIONS/SIGNIFICANCE: After the development of an
      appropriate database, MALDI-TOF-MS can be used to identify tick species and the
      presence of relapsing fever borreliae in a single assay. This work paves the way
      for the use of MALDI-TOF-MS for the dual identification of vectors and vectorized
      pathogens.

PMID- 25058612
TI  - When concepts lose their color: a case of object-color knowledge impairment.
AB  - Color is important in our daily interactions with objects, and plays a role in
      both low- and high-level visual processing. Previous neuropsychological studies
      have shown that color perception and object-color knowledge can doubly
      dissociate, and that both can dissociate from processing of object form. We
      present a case study of an individual who displayed an impairment for knowledge
      of the typical colors of objects, with preserved color perception and color
      naming. Our case also presented with a pattern of, if anything, worse performance
      for naming living items compared to non-living things. The findings of the
      experimental investigation are evaluated in light of two theories of conceptual
      organization in the brain: the Sensory/Functional Theory and the Domain-Specific
      Hypothesis. The dissociations observed in this case compel a model in which
      sensory/motor modality and semantic domain jointly constrain the organization of
      object knowledge. 

PMID- 25058614
TI  - Total anomalous pulmonary venous connection in a neonate characterised by low
      dose, high-pitch cardiac CT.
AB  - We describe the use of low-dose dual-source cardiac for the evaluation of a
      neonate with suspected total anomalous pulmonary venous connection. This novel
      technique obviates the need for sedation or breathholding. Radiation dose
      reduction strategies result in sub-mSv-estimated effective doses, substantially
      lower than annual background radiation dose. Low-dose, high-pitch cardiac CT
      should be considered as an alternative to MRI or diagnostic cardiac
      catheterisation in neonates with complex CHD, requiring definitive anatomic
      evaluation. 

PMID- 25058613
TI  - Characterising the inhibitory actions of ceramide upon insulin signaling in
      different skeletal muscle cell models: a mechanistic insight.
AB  - Ceramides are known to promote insulin resistance in a number of metabolically
      important tissues including skeletal muscle, the predominant site of insulin
      stimulated glucose disposal. Depending on cell type, these lipid intermediates
      have been shown to inhibit protein kinase B (PKB/Akt), a key mediator of the
      metabolic actions of insulin, via two distinct pathways: one involving the action
      of atypical protein kinase C (aPKC) isoforms, and the second dependent on protein
      phosphatase-2A (PP2A). The main aim of this study was to explore the mechanisms
      by which ceramide inhibits PKB/Akt in three different skeletal muscle-derived
      cell culture models; rat L6 myotubes, mouse C2C12 myotubes and primary human
      skeletal muscle cells. Our findings indicate that the mechanism by which ceramide
      acts to repress PKB/Akt is related to the myocellular abundance of caveolin
      enriched domains (CEM) present at the plasma membrane. Here, we show that
      ceramide-enriched-CEMs are markedly more abundant in L6 myotubes compared to
      C2C12 myotubes, consistent with their previously reported role in coordinating
      aPKC-directed repression of PKB/Akt in L6 muscle cells. In contrast, a PP2A
      dependent pathway predominantly mediates ceramide-induced inhibition of PKB/Akt
      in C2C12 myotubes. In addition, we demonstrate for the first time that ceramide
      engages an aPKC-dependent pathway to suppress insulin-induced PKB/Akt activation
      in palmitate-treated cultured human muscle cells as well as in muscle cells from
      diabetic patients. Collectively, this work identifies key mechanistic
      differences, which may be linked to variations in plasma membrane composition,
      underlying the insulin-desensitising effects of ceramide in different skeletal
      muscle cell models that are extensively used in signal transduction and metabolic
      studies. 

PMID- 25058615
TI  - IL-17A production in human psoriatic blood and lesions by CD146+ T cells.

PMID- 25058616
TI  - A one-pot synthetic strategy for construction of the dibenzodiazepine skeleton
      via a transition metal-free process.
AB  - A one-pot transition metal-free methodology for constructing pharmacologically
      active dibenzodiazepine derivatives was developed. Fluoro-, bromo- and nitro
      substituted aryl aldehydes were applied to this reaction efficiently. 

PMID- 25058618
TI  - Increased noise levels have different impacts on the anti-predator behaviour of
      two sympatric fish species.
AB  - Animals must avoid predation to survive and reproduce, and there is increasing
      evidence that man-made (anthropogenic) factors can influence predator-prey
      relationships. Anthropogenic noise has been shown to have a variety of effects on
      many species, but work investigating the impact on anti-predator behaviour is
      rare. In this laboratory study, we examined how additional noise (playback of
      field recordings of a ship passing through a harbour), compared with control
      conditions (playback of recordings from the same harbours without ship noise),
      affected responses to a visual predatory stimulus. We compared the anti-predator
      behaviour of two sympatric fish species, the three-spined stickleback
      (Gasterosteus aculeatus) and the European minnow (Phoxinus phoxinus), which share
      similar feeding and predator ecologies, but differ in their body armour. Effects
      of additional-noise playbacks differed between species: sticklebacks responded
      significantly more quickly to the visual predatory stimulus during additional
      noise playbacks than during control conditions, while minnows exhibited no
      significant change in their response latency. Our results suggest that elevated
      noise levels have the potential to affect anti-predator behaviour of different
      species in different ways. Future field-based experiments are needed to confirm
      whether this effect and the interspecific difference exist in relation to real
      world noise sources, and to determine survival and population consequences. 

PMID- 25058617
TI  - The cellular prion protein negatively regulates phagocytosis and cytokine
      expression in murine bone marrow-derived macrophages.
AB  - The cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI)
      anchored glycoprotein on the cell surface. Previous studies have demonstrated
      contradictory roles for PrP(C) in connection with the phagocytic ability of
      macrophages. In the present work, we investigated the function of PrP(C) in
      phagocytosis and cytokine expression in bone marrow-derived macrophages infected
      with Escherichia coli. E. coli infection induced an increase in the PRNP mRNA
      level. Knockout of PrP(C) promoted bacterial uptake; upregulated Rab5, Rab7, and
      Eea1 mRNA expression; and increased the recruitment of lysosomal-associated
      membrane protein-2 to phagosomes, suggesting enhanced microbicidal activity.
      Remarkably, knockout of PrP(C) suppressed the proliferation of internalized
      bacteria and increased the expression of cytokines such as interleukin-1beta.
      Collectively, our data reveal an important role of PrP(C) as a negative regulator
      for phagocytosis, phagosome maturation, cytokine expression, and macrophage
      microbicidal activity.

PMID- 25058620
TI  - Comparison of human menopausal gonadotropin stimulation with and without
      clomiphene for in-vitro fertilisation in poor-responders.
AB  - This study aimed to determine the effectiveness of human menopausal gonadotropin
      (hMG) with and without clomiphene citrate (CC) for ovarian stimulation and oocyte
      retrieval in poor-responders. A total of 66 cycles in 13 patients met the
      inclusion criteria of 20 cycles of hMG stimulation and 46 cycles of CC + hMG
      stimulation. Mean total hMG dose per patient was significantly lower during the
      stimulation cycle with CC + hMG than with hMG alone. Mean oestradiol level at
      oocyte retrieval and mean number of oocytes retrieved per patient showed no
      significant differences between the two cycles. Four of the 13 patients achieved
      pregnancy with the CC + hMG cycles. The absence of a significant difference in
      oestradiol level at oocyte retrieval or in the number of oocytes retrieved
      between the two cycles, despite a significantly lower total hMG dose during the
      CC + hMG stimulation cycles, suggests a greater benefit of CC + hMG stimulation
      for poor-responders.

PMID- 25058619
TI  - Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete
      neutralization.
AB  - Human antibody 10E8 targets the conserved membrane proximal external region
      (MPER) of envelope glycoprotein (Env) subunit gp41 and neutralizes HIV-1 with
      exceptional potency. Remarkably, HIV-1 containing mutations that reportedly
      knockout 10E8 binding to linear MPER peptides are partially neutralized by 10E8,
      producing a local plateau in the dose response curve. Here, we found that virus
      partially neutralized by 10E8 becomes significantly less neutralization sensitive
      to various MPER antibodies and to soluble CD4 while becoming significantly more
      sensitive to antibodies and fusion inhibitors against the heptad repeats of gp41.
      Thus, 10E8 modulates sensitivity of Env to ligands both pre- and post-receptor
      engagement without complete neutralization. Partial neutralization by 10E8 was
      influenced at least in part by perturbing Env glycosylation. With unliganded Env,
      10E8 bound with lower apparent affinity and lower subunit occupancy to MPER
      mutant compared to wild type trimers. However, 10E8 decreased functional
      stability of wild type Env while it had an opposite, stabilizing effect on MPER
      mutant Envs. Clade C isolates with natural MPER polymorphisms also showed partial
      neutralization by 10E8 with altered sensitivity to various gp41-targeted ligands.
      Our findings suggest a novel mechanism of virus neutralization by demonstrating
      how antibody binding to the base of a trimeric spike cross talks with adjacent
      subunits to modulate Env structure and function. The ability of an antibody to
      stabilize, destabilize, partially neutralize as well as alter neutralization
      sensitivity of a virion spike pre- and post-receptor engagement may have
      implications for immunotherapy and vaccine design. 

PMID- 25058621
TI  - The relationship of dominance, reproductive state and stress in female horses
      (Equus caballus).
AB  - Maintaining a dominant position in a hierarchy requires energetically expensive
      aggressive displays and physical exertion. Lab based winner-loser studies, often
      conducted with individuals from non-social species, have shown that subordinates
      have higher stress hormone levels than dominant individuals. However, in wild
      studies on cooperative breeders, displays of aggression used to maintain
      dominance status are associated with elevated stress hormone levels. The effect
      of reproductive state on dominance and stress has not been addressed within
      either of these situations. The purpose of this study was to examine
      physiological stress levels in relation to dominance rank and reproductive state
      in a non-cooperative breeder and herbivore, the domestic horse. The social
      interactions and measured faecal glucocorticoids were recorded in pastured,
      female horses that were either lactating or non-lactating. While faecal
      glucocorticoid metabolite level did not differ between reproductive state and
      rank, activity behaviour demonstrated significant differences between
      reproductive states. Higher energetic requirements of lactation were reflected in
      significantly longer bouts of eating and significantly less time spent alert and
      socializing. As non-cooperative breeders, the social nature of horses does not
      limit their reproduction or resource acquisition based upon rank, and therefore
      does not fit with the dominance-stress hypothesis or subordinate-stress
      hypothesis and instead supports a rank-independent stress hypothesis. 

PMID- 25058622
TI  - Laboratory studies of imitation/field studies of tradition: towards a synthesis
      in animal social learning.
AB  - Here I discuss: (1) historical precedents that have resulted in comparative
      psychologists accepting the two-action method as the "gold standard" in
      laboratory investigations of imitation learning, (2) evidence suggesting that the
      two-action procedure may not be adequate to answer questions concerning the role
      of imitation in the development of traditional behaviors of animals living in
      natural habitat, and (3) an alternative approach to the laboratory study of
      imitation that might increase the relevance of laboratory studies of imitation to
      the work of behavioral ecologists/primatologists interested in animal traditions
      and their relationship to human cumulative culture. This article is part of a
      Special Issue entitled: Tribute to Tom Zentall. 

PMID- 25058623
TI  - Cerebral cortical activity associated with non-experts' most accurate motor
      performance.
AB  - This study's specific aim was to determine if non-experts' most accurate motor
      performance is associated with verbal-analytic- and working memory-related
      cerebral cortical activity during motor preparation. To assess this, EEG was
      recorded from non-expert golfers executing putts; EEG spectral power and
      coherence were calculated for the epoch preceding putt execution; and spectral
      power and coherence for the five most accurate putts were contrasted with that
      for the five least accurate. Results revealed marked power in the theta frequency
      bandwidth at all cerebral cortical regions for the most accurate putts relative
      to the least accurate, and considerable power in the low-beta frequency bandwidth
      at the left temporal region for the most accurate compared to the least. As theta
      power is associated with working memory and low-beta power at the left temporal
      region with verbal analysis, results suggest non-experts' most accurate motor
      performance is associated with verbal-analytic- and working memory-related
      cerebral cortical activity during motor preparation.

PMID- 25058624
TI  - Physiological and perceptual responses to Latin partnered social dance.
AB  - The purpose of this study was to investigate the physiological and perceptual
      responses to Latin partnered social dance to salsa music when performed as a self
      selected activity within an ecologically valid setting. Eighteen non-professional
      adult Latin dancers undertook a laboratory-based graded exercise test for
      determination of maximal oxygen uptake and maximal heart rate. The dancers then
      attended two Latin partnered social dance sessions in established salsa venues in
      London, UK over a 2 wk period. Physiological data were collected using a wrist
      worn ActiGraph wGT3X+ accelerometer with accompanying heart rate monitor.
      Perceived benefits of dance were assessed via the Exercise Benefits/Barriers
      Scale, and measurement of state intrinsic motivation during dance was undertaken
      using the Intrinsic Motivation Inventory. Total step count during 2h of dance was
      not different (t16 = -.39, p = .71) between females and males (9643 +/- 1735
      step); however, women expended a significantly lower (t16 = -2.57, p < .05) total
      energy expenditure when compared to men (479 +/- 125 versus 651 +/- 159 kcal).
      Dancers of both genders considered interest-enjoyment to be the motivator of
      primary importance. The highest rated perceived benefit of dance was
      psychological outlook. Latin partnered social dance to salsa music demands
      moderate to vigorous physical activity intensity levels, and further, fosters
      interest, enjoyment, and a positive psychological outlook among novice to
      advanced adult Latin dancers taking part primarily for leisure purposes. These
      findings may be of use for those interested in the efficacy of Latin social
      dancing as an expressive medium for the promotion of community health.

PMID- 25058625
TI  - Timing accuracy in self-timed movements related to neural indicators of movement
      initiation.
AB  - Timely movement initiation is crucial in quick reactions or when a series of
      movements has to be strung together in a timed fashion to create a coordinated
      sequence. Stochastic neural variability can lead to misinitiation errors as
      reaction time studies suggest. Higher reaction times occur when preparatory
      neural activity reaches an initiation threshold later relative to shorter
      reaction times. Whether this also applies to self-timed movements is harder to
      scrutinize because they lack an external event that could serve as a reference
      for timing accuracy estimations. By example of a self-timed goal-oriented
      throwing task, we used a method that synchronizes the throwing movements by their
      kinematic profiles to assess relative timing differences in throwing release. We
      determined neural preparatory processes of the release using the movement-related
      electrophysiological Bereitschaftspotential (BP). By analyzing differences in
      shape and timing of the BP in delayed and non-delayed throws, two variables could
      be extracted that are related to timing differences on the kinematic level.
      First, temporal deviations in BP curves partly meet the kinematic deviations.
      Second, delayed releases were preceded by a short flattening of the BP curves
      prior to release. Thus, temporal and shape deviations in the neural movement
      initiation are assumed to delay self-timed movements.

PMID- 25058626
TI  - Chemometric evaluation of trace metal concentrations in some nuts and seeds.
AB  - Seventeen trace metals in acid digests of nuts and seeds were determined using
      inductively coupled plasma-atomic emission spectrometry and inductively coupled
      plasma-mass spectrometry. The data were subjected to chemometric evaluation using
      principal component analysis (PCA), linear discriminant analysis (LDA) and
      cluster analysis (CA) in an attempt to classify the samples. Hazelnuts (raw and
      dry roasted), almonds (raw and dry roasted), sunflower seeds (black and white),
      peanuts (raw and dry roasted), cashew nuts, Brazil nuts, walnuts, chickpeas (raw
      and dry roasted), pumpkin seeds (raw and dry roasted), and pistachio nuts were
      used as samples. The samples were classified into seven groups by PCA and CA. All
      group members determined using PCA and CA were found by LDA to be correctly
      classified in the predicted groups. Interestingly, the chemometric evaluation
      indicated that the raw and roasted nuts are very close to each other even though
      some originated from different countries. 

PMID- 25058627
TI  - Does surgery improve live birth rates in patients with recurrent miscarriage
      caused by uterine anomalies?
AB  - We found that congenital uterine anomalies have a negative impact on reproductive
      outcome in recurrent-miscarriage couples, being associated with further
      miscarriage with a normal embryonic karyotype. There has been no study comparing
      live birth rates between patients with and without surgery. We conducted a
      prospective study to prove that surgery for a bicornuate or septate uterus might
      improve the live birth rate. A total of 170 patients with congenital uterine
      anomalies suffering two or more miscarriages were examined. The live birth rate
      after ascertainment of anomalies, cumulative live birth rate and infertility
      rate, were compared between patients with and without surgery. In patients with a
      septate uterus, the live birth rate (81.3%) at the first pregnancy after
      ascertainment of anomalies with surgery tended to be higher than that (61.5%) in
      those without surgery. The infertility rates were similar in both groups, while
      the cumulative live birth rate (76.1%) tended to be higher than without surgery
      (60.0%). Surgery showed no benefit in patients with a bicornuate uterus for
      having a baby, but tended to decrease the preterm birth rate and the low birth
      weight. The possibility that surgery has benefits for having a baby in patients
      with a septate uterus suffering recurrent miscarriage could not be excluded.

PMID- 25058628
TI  - Emotional Stroop interference in trauma-exposed individuals: a contrast between
      two accounts.
AB  - In the Emotional Stroop task, trauma-exposed victims are slowed when naming the
      colour print of trauma-related words, showing the presence of interference. This
      interference has been assumed to reflect emotional reactions triggered by
      experience-relevant emotional content which interfere with the task. However, it
      may equally reflect the activation of task-competing thoughts triggered by
      experience-relevant semantic content, thus resulting from cognitive- rather than
      emotion-driven processes. This study contrasted these possibilities by measuring
      the relationship between Emotional Stroop interference, on the one hand, and
      severity of sexual-abuse experience, subjective ratings of emotionality, and
      working-memory measures, on the other. Whereas there was no relationship between
      working-memory measures and interference, providing no support for the cognitive
      based account, experience severity, emotionality ratings and abuse-related
      interference were all positively related, providing support for the emotion-based
      account. These findings support the idea that the Emotional Stroop task can be
      used as a diagnostic tool for emotion-filtering impairment. 

PMID- 25058629
TI  - A comparison between a visual analogue scale and a four point scale as measures
      of conscious experience of motion.
AB  - Can participants make use of the large number of response alternatives of visual
      analogue scales (VAS) when reporting their subjective experience of motion? In a
      new paradigm, participants adjusted a comparison according to random dot
      kinematograms with the direction of motion varying between 0 degrees  and 360
      degrees . After each discrimination response, they reported how clearly they
      experienced the global motion either using a VAS or a discrete scale with four
      scale steps. We observed that both scales were internally consistent and were
      used gradually. The visual analogue scale was more efficient in predicting
      discrimination error but this effect was mediated by longer report times and was
      no longer observed when the VAS was discretized into four bins. These
      observations are consistent with the interpretation that VAS and discrete scales
      are associated with a comparable degree of metacognitive sensitivity, although
      the VAS provides a greater amount of information. 

PMID- 25058630
TI  - Studying the mechanism of CD47-SIRPalpha interactions on red blood cells by
      single molecule force spectroscopy.
AB  - The interaction forces and binding kinetics between SIRPalpha and CD47 were
      investigated by single-molecule force spectroscopy (SMFS) on both fresh and
      experimentally aged human red blood cells (hRBCs). We found that CD47 experienced
      a conformation change after oxidation, which influenced the interaction force and
      the position of the energy barrier between SIRPalpha and CD47. Our results are
      significant for understanding the mechanism of phagocytosis of red blood cells at
      the single molecule level. 

PMID- 25058631
TI  - An AMD treasure trove publication and new strength for OVS.

PMID- 25058632
TI  - Age-related macular degeneration: what's new and on the horizon.

PMID- 25058637
TI  - Is the risk of motor neuron disease increased or decreased after cancer? An
      Australian case-control study.
AB  - Cancer appears to be inversely associated with both Alzheimer's and Parkinson's
      disease. The relationship between cancer and sporadic motor neuron disease
      (SMND), however, remains uncertain. Most previous cancer-SMND studies have been
      undertaken in northern hemisphere populations. We therefore undertook a case
      control study to see if a link between cancer and SMND exists in an Australian
      population. A questionnaire was used to compare past cancer diagnoses in 739 SMND
      patients and 622 controls, recruited across Australia. Odds ratios with 95%
      confidence intervals were calculated to look for associations between cancer and
      SMND. A history of cancer was not associated either positively or negatively with
      a risk of subsequent SMND. This result remained when age, gender, smoking status,
      and the four SMND diagnostic subgroups were taken into account. No association
      was observed between SMND and specific tumours, including melanoma, a common
      malignancy in Australia. In conclusion, this Australian case-control study does
      not support an association between a past history of cancer and the development
      of SMND. This suggests that some pathogenetic mechanisms, such as apoptosis, are
      less relevant in SMND than in other neurodegenerative diseases where negative
      associations with cancer have been found. 

PMID- 25058638
TI  - Functional diversification of hsp40: distinct j-protein functional requirements
      for two prions allow for chaperone-dependent prion selection.
AB  - Yeast prions are heritable amyloid aggregates of functional yeast proteins; their
      propagation to subsequent cell generations is dependent upon fragmentation of
      prion protein aggregates by molecular chaperone proteins. Mounting evidence
      indicates the J-protein Sis1 may act as an amyloid specificity factor,
      recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act
      in prion fragmentation. Chaperone interactions with prions, however, can be
      affected by variations in amyloid-core structure resulting in distinct prion
      variants or 'strains'. Our genetic analysis revealed that Sis1 domain
      requirements by distinct variants of [PSI+] are strongly dependent upon overall
      variant stability. Notably, multiple strong [PSI+] variants can be maintained by
      a minimal construct of Sis1 consisting of only the J-domain and
      glycine/phenylalanine-rich (G/F) region that was previously shown to be
      sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak
      [PSI+] variants are lost under the same conditions but maintained by the
      expression of an Sis1 construct that lacks only the G/F region and cannot support
      [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function
      between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or
      dependent upon a particular yeast genetic background. These observations
      necessitate that Sis1 must have at least two distinct functional roles that
      individual prions differentially require for propagation and which are localized
      to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1
      plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion
      selection for either prion. We also found that, despite an initial report to the
      contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation
      in place of Sis1. This conservation of function is also prion-variant dependent,
      indicating that only one of the two Sis1-prion functions may have been maintained
      in eukaryotic chaperone evolution. 

PMID- 25058639
TI  - Cellular changes in blood indicate severe respiratory disease during influenza
      infections in mice.
AB  - Influenza A infection is a serious threat to human and animal health. Many of the
      biological mechanisms of the host-pathogen-interactions are still not well
      understood and reliable biomarkers indicating the course of the disease are
      missing. The mouse is a valuable model system enabling us to study the local
      inflammatory host response and the influence on blood parameters under controlled
      circumstances. Here, we compared the lung and peripheral changes after PR8 (H1N1)
      influenza A virus infection in C57BL/6J and DBA/2J mice using virus variants of
      different pathogenicity resulting in non-lethal and lethal disease. We monitored
      hematological and immunological parameters revealing that the granulocyte to
      lymphocyte ratio in the blood represents an early indicator of severe disease
      progression already two days after influenza A infection in mice. These findings
      might be relevant to optimize early diagnostic options of severe influenza
      disease and to monitor successful therapeutic treatment in humans. 

PMID- 25058641
TI  - Striving for excellence while adapting to change: redefining our mission of
      serving the preventive medicine community.

PMID- 25058640
TI  - Analysis of stop-gain and frameshift variants in human innate immunity genes.
AB  - Loss-of-function variants in innate immunity genes are associated with Mendelian
      disorders in the form of primary immunodeficiencies. Recent resequencing projects
      report that stop-gains and frameshifts are collectively prevalent in humans and
      could be responsible for some of the inter-individual variability in innate
      immune response. Current computational approaches evaluating loss-of-function in
      genes carrying these variants rely on gene-level characteristics such as
      evolutionary conservation and functional redundancy across the genome. However,
      innate immunity genes represent a particular case because they are more likely to
      be under positive selection and duplicated. To create a ranking of severity that
      would be applicable to innate immunity genes we evaluated 17,764 stop-gain and
      13,915 frameshift variants from the NHLBI Exome Sequencing Project and 1,000
      Genomes Project. Sequence-based features such as loss of functional domains,
      isoform-specific truncation and nonsense-mediated decay were found to correlate
      with variant allele frequency and validated with gene expression data. We
      integrated these features in a Bayesian classification scheme and benchmarked its
      use in predicting pathogenic variants against Online Mendelian Inheritance in Man
      (OMIM) disease stop-gains and frameshifts. The classification scheme was applied
      in the assessment of 335 stop-gains and 236 frameshifts affecting 227 interferon
      stimulated genes. The sequence-based score ranks variants in innate immunity
      genes according to their potential to cause disease, and complements existing
      gene-based pathogenicity scores. Specifically, the sequence-based score improves
      measurement of functional gene impairment, discriminates across different
      variants in a given gene and appears particularly useful for analysis of less
      conserved genes. 

PMID- 25058642
TI  - In situ simultaneous monitoring of ATP and GTP using a graphene oxide nanosheet
      based sensing platform in living cells.
AB  - Here we present a detailed protocol for in situ multiple fluorescence monitoring
      of adenosine-5'-triphosphate (ATP) and guanosine-5'-triphosphate (GTP) in MCF-7
      breast cancer cells by using graphene oxide nanosheet (GO-nS) and DNA/RNA
      aptamers. FAM-labeled ATP aptamer and Cy5-modified GTP aptamer are used to
      construct the multiple aptamer/GO-nS sensing platform through 'pi-pi stacking'
      between aptamers and GO-nS. Binding of aptamers to GO-nS guarantees the
      fluorescence resonance energy transfer between fluorophores and GO-nS, resulting
      in 'fluorescence off'. When the aptamer/GO-nS are transported inside the cells
      via endocytosis, the conformation of the aptamers will change on interaction with
      cellular ATP and GTP. On the basis of the fluorescence 'off/on' switching,
      simultaneous sensing and imaging of ATP and GTP in vitro and in situ have been
      realized through fluorescence and confocal microscopy techniques. In this
      protocol, we describe the synthesis of GO and GO-nS, preparation of aptamer/GO-nS
      platform, in vitro detection of ATP and GTP, and how to use this platform to
      realize intracellular ATP and GTP imaging in cultured MCF-7 cells. The
      preparation of GO-nS is anticipated to take 7-14 d, and assays involving
      microscopy imaging and MCF-7 cells culturing can be performed in 2-3 d. 

PMID- 25058643
TI  - Generating genetically modified mice using CRISPR/Cas-mediated genome
      engineering.
AB  - Mice with specific gene modifications are valuable tools for studying development
      and disease. Traditional gene targeting in mice using embryonic stem (ES) cells,
      although suitable for generating sophisticated genetic modifications in
      endogenous genes, is complex and time-consuming. We have recently described
      CRISPR/Cas-mediated genome engineering for the generation of mice carrying
      mutations in multiple genes, endogenous reporters, conditional alleles or defined
      deletions. Here we provide a detailed protocol for embryo manipulation by piezo
      driven injection of nucleic acids into the cytoplasm to create gene-modified
      mice. Beginning with target design, the generation of gene-modified mice can be
      achieved in as little as 4 weeks. We also describe the application of the
      CRISPR/Cas technology for the simultaneous editing of multiple genes (five genes
      or more) after a single transfection of ES cells. The principles described in
      this protocol have already been applied in rats and primates, and they are
      applicable to sophisticated genome engineering in species in which ES cells are
      not available. 

PMID- 25058644
TI  - Measurement of methylglyoxal by stable isotopic dilution analysis LC-MS/MS with
      corroborative prediction in physiological samples.
AB  - This protocol describes a method for the detection and quantification of
      methylglyoxal (MG), the major physiological substrate of the cytosolic glyoxalase
      system. Accumulation of MG, also called dicarbonyl stress, is implicated in
      tissue damage in aging and disease. Measurement of MG is important in
      physiological studies, in the development of glyoxalase 1 (Glo1) inducer and
      inhibitor therapeutics, and in the characterization of medical products,
      especially dialysis fluids, and of thermally processed foods and beverages. MG
      can be derivatized with 1,2-diaminobenzene (DB), resulting in an adduct that can
      be detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Quantification is achieved by stable isotopic dilution analysis with [(13)C3]MG.
      Pre-analytic processing at ambient temperature, under acidic conditions with
      peroxidase inhibition, avoids artifactual overestimation of MG. Estimates
      obtained from physiological samples can be validated by kinetic modeling of in
      situ rates of protein glycation by MG for confirmation of the results. This
      procedure was developed for the analysis of cultured cells, plasma and animal
      tissue samples, and it can also be used to analyze plant material. Experimental
      measurement requires 4.5 h for sample batch pre-analytic processing and 30 min
      per sample for LC-MS/MS analysis. 

PMID- 25058645
TI  - Production and quantification of sesquiterpenes in Saccharomyces cerevisiae,
      including extraction, detection and quantification of terpene products and key
      related metabolites.
AB  - The procedures described here are designed for engineering Saccharomyces
      cerevisiae to produce sesquiterpenes with an aim to either increase product
      titers or to simply generate a quantity of product sufficient for identification
      and/or downstream experimentation. Engineering high-level sesquiterpene
      production in S. cerevisiae often requires iterations of strain modifications and
      metabolite analysis. To address the latter, the methods described here were
      tailored for robust measurement of metabolites that we have found to be
      fundamental indicators of pathway flux, using only gas chromatography and mass
      spectrometry (GC-MS) instrumentation. Thus, by focusing on heterologous
      production of sesquiterpenes via the mevalonate (MEV) pathway in S. cerevisiae,
      we detail procedures for extraction and detection of the key pathway metabolites
      MEV, squalene and ergosterol, as well as the farnesyl pyrophosphate (FPP)-derived
      side products farnesol and nerolidol. Analysis of these compounds is important
      for quality control, because they are possible indicators of pathway imbalance.
      As many of the sesquiterpene synthase (STS) genes encountered in nature are of
      plant origin and often not optimal for expression in yeast, we provide guidelines
      for designing gene expression cassettes to enable expression in S. cerevisiae. As
      a case study for these protocols, we have selected the sesquiterpene
      amorphadiene, native to Artemisia annua and related plants. The analytical steps
      can be completed within 1-2 working days, and a typical experiment might take 1
      week. 

PMID- 25058646
TI  - Measuring surface potential changes on leaves.
AB  - We provide here a detailed protocol for studying the changes in electrical
      surface potential of leaves. This method has been developed over the years by
      plant physiologists and is currently used in different variants in many
      laboratories. The protocol records surface potential changes to measure long
      distance electrical signals induced by diverse stimuli such as leaf wounding or
      current injection. This technique can be used to determine signaling speeds, to
      measure the connectivity between different plant organs and-by exploiting mutant
      plants-to identify transporters and ion channels involved in electrical
      signaling. The approach can be combined with the analysis of mRNA expression and
      of metabolite concentrations to correlate electrical signaling to specific
      physiological events. We describe how to use this protocol on Arabidopsis,
      looking at the effects of leaf wounding; however, it is broadly applicable to
      other plants and can be used to study other aspects of plant physiology. After
      wound infliction, surface potential recording takes ~20 min per plant. 

PMID- 25058647
TI  - Novel RAFT amphiphilic brush copolymer steric stabilisers for cubosomes:
      poly(octadecyl acrylate)-block-poly(polyethylene glycol methyl ether acrylate).
AB  - Copolymers, particularly Pluronics(r), are typically used to sterically stabilise
      colloidal nanostructured particles composed of a lyotropic liquid crystalline
      bicontinuous cubic phase (cubosomes). There is a need to design and assess new
      functionalisable stabilisers for these colloidal drug delivery systems. Six
      amphiphilic brush copolymers, poly(octadecyl acrylate)-block-poly(polyethylene
      glycol methyl ether acrylate) (P(ODA)-b-P(PEGA-OMe)), synthesised by reversible
      addition-fragmentation chain transfer (RAFT), were assessed as novel steric
      stabilisers for cubosomes. It was found that increasing the density of PEG on the
      nanostructured particle surface by incorporating a PEG brush design (i.e., brush
      copolymer), provided comparable and/or increased stabilisation effectiveness
      compared to a linear PEG structure, Pluronic(r) F127, which is extensively used
      for steric stabilisation of cubosomes. Assessment was conducted both prior to and
      following the removal of the dodecyl trithiocarbonate end-group, by free radical
      induced reduction. The reduced (P(ODA)-b-P(PEGA-OMe) copolymers were more
      effective steric stabilisers for phytantriol and monoolein colloidal particle
      dispersions than their non-reduced analogues. High throughput characterisation
      methodologies, including an accelerated stability assay (ASA) and synchrotron
      small angle X-ray scattering (SAXS), were implemented in this study for the rapid
      assessment of steric stabiliser effectiveness and lyotropic liquid crystalline
      phase identification. Phytantriol cubosomes stabilised with P(ODA)-b-P(PEGA-OMe)
      copolymers exhibited a double diamond cubic phase (Q(2)(D)), whilst monoolein
      cubosomes exhibited a primitive cubic phase (Q(2)(P)), analogous to those formed
      using Pluronic(r) F127.

PMID- 25058648
TI  - Misperception of self-reported adherence to the fruit, vegetable and fish
      guidelines in older Dutch adults.
AB  - In this study we investigated (the degree of) misperception of adherence to the
      fruit, vegetable and fish guidelines in older Dutch adults and examined to what
      extent misperception is associated with socio-economic position (SEP) and other
      demographic, lifestyle and nutrition-related characteristics. The sample included
      1057 community dwelling adults, aged 55-85 years, who participated in the
      Longitudinal Aging Study Amsterdam. Respondents completed a lifestyle
      questionnaire which included a food frequency questionnaire to calculate fruit,
      vegetable and fish intake. After current dietary guidelines were explained,
      respondents were asked to indicate whether they believed they adhered to the
      fruit, vegetable and fish guidelines. Characteristics potentially associated with
      misperception included level of income and education, lifestyle factors,
      nutritional knowledge, as well as attitude, social support and self-efficacy
      toward healthy eating. In the total sample, 69.1% of the older adults reported to
      adhere to the fruit guideline, 77.5% to the vegetable guideline, and 36.4% to the
      fish guideline. Based on the calculated intake data, 82.6% adhered to the fruit
      guideline, 65.5% to the vegetable guideline and 33.8% to the fish guideline.
      Overestimation of adherence was most common for the vegetable guideline (18.7%).
      Multivariate analysis, adjusted for level of income as well as for attitude and
      self-efficacy toward healthy eating, showed that lower educated respondents were
      more likely to overestimate their adherence to the vegetable guideline (relative
      index of inequality (RII): 2.97 (95% CI: 1.47-6.01)). Overestimation rates for
      fish (3.4%) and fruit (2.3%) were lower and not associated with any of the
      characteristics. This study showed that overestimation in older adults was common
      for adherence to the vegetable guideline and especially in those with a lower
      education level, but not for adherence to the fruit and fish guideline. 

PMID- 25058649
TI  - Testing the original and the extended dual-pathway model of lack of control over
      eating in adolescent girls. A two-year longitudinal study.
AB  - Stice's (1994, 2001) dual pathway model proposed a mediational sequence that
      links body dissatisfaction to lack of control over eating through dieting and
      negative affect. Van Strien et al. (2005) extended the negative affect pathway of
      the original dual pathway model by adding two additional intervening variables:
      interoceptive deficits and emotional eating. The purpose of this study was to
      test and compare the original and extended model using prospective data. Both
      types of loss of control over eating (i.e., subjective and objective binge
      eating) were evaluated. Data collected from 361 adolescent girls, who were
      interviewed and completed self-report measures annually over a 2-year period,
      were analysed using structural equation modeling. Although both models provided a
      good fit to the data, the extended model fit the adolescent girls' sample data
      better and accounted for a greater proportion of variance in binge eating than
      the original model. All proposed mediational pathways of both models were
      supported and all indirect effects examined through bootstrap procedure were
      significant. Although our results confirmed the validity of both models and
      extended previous findings to an early- to middle adolescent group, the bi
      directional relationship between dietary restriction and negative affect suggests
      that the association between these key risk factors for binge eating are more
      complex than outlined in both the original and extended dual-pathway models. 

PMID- 25058651
TI  - Effects of germanium biotite supplement on immune responses of vaccinated mini
      pigs to foot-and-mouth disease virus challenge.
AB  - Since the outbreaks of foot-and-mouth disease (FMD) in South Korea in 2010-2011,
      a trivalent vaccine has been used as a routine vaccination. Despite the high
      efficacy of the trivalent vaccine, low antibody formation was reported in the pig
      industry and there is considerable concern about the ability of the vaccine to
      protect against the Andong strain responsible for recent outbreaks in South
      Korea. To overcome these problems, immunostimulators have been widely used to
      improve vaccine efficacy in South Korea, although without any scientific
      evidence. Based on the current situation, the aim of this study was to
      investigate the effects of germanium biotite, a feed supplement used to enhance
      the immune system, on the immune responses to FMD vaccination through the Andong
      strain challenge experiment in trivalent vaccinated pigs. Following the
      challenge, the germanium biotite-fed pigs showed high levels of IL-8 in serum,
      and increased cellular immune responses to stimulation with the Andong strain
      antigen compared to nonsupplemented pigs. In addition, higher FMD virus (FMDV)
      neutralizing antibody titers were detected in the germanium biotite-fed group
      than in the nonsupplemented group before the challenge. The findings of this
      study indicate that germanium biotite supplement might enhance immune responses
      to the FMD vaccine in pigs. 

PMID- 25058650
TI  - LITAF mutations associated with Charcot-Marie-Tooth disease 1C show
      mislocalization from the late endosome/lysosome to the mitochondria.
AB  - Charcot-Marie-Tooth (CMT) disease is one of the most common heritable
      neuromuscular disorders, affecting 1 in every 2500 people. Mutations in LITAF
      have been shown to be causative for CMT type 1C disease. In this paper we explore
      the subcellular localization of wild type LITAF and mutant forms of LITAF known
      to cause CMT1C (T49M, A111G, G112S, T115N, W116G, L122V and P135T). The results
      show that LITAF mutants A111G, G112S, W116G, and T115N mislocalize from the late
      endosome/lysosome to the mitochondria while the mutants T49M, L122V, and P135T
      show partial mislocalization with a portion of the total protein present in the
      late endosome/lysosome and the remainder of the protein localized to the
      mitochondria. This suggests that different mutants of LITAF will produce
      differing severity of disease. We also explored the effect of the presence of
      mutant LITAF on wild-type LITAF localization. We showed that in cells
      heterozygous for LITAF, CMT1C mutants T49M and G112S are dominant since wild-type
      LITAF localized to the mitochondria when co-transfected with a LITAF mutant.
      Finally, we demonstrated how LITAF transits to the endosome and mitochondria
      compartments of the cell. Using Brefeldin A to block ER to Golgi transport we
      demonstrated that wild type LITAF traffics through the secretory pathway to the
      late endosome/lysosome while the LITAF mutants transit to the mitochondria
      independent of the secretory pathway. In addition, we demonstrated that the C
      terminus of LITAF is necessary and sufficient for targeting of wild-type LITAF to
      the late endosome/lysosome and the mutants to the mitochondria. Together these
      data provide insight into how mutations in LITAF cause CMT1C disease. 

PMID- 25058652
TI  - Analyzing cold tolerance mechanism in transgenic zebrafish (Danio rerio).
AB  - Low temperatures may cause severe growth inhibition and mortality in fish. In
      order to understand the mechanism of cold tolerance, a transgenic zebrafish Tg
      (smyd1:m3ck) model was established to study the effect of energy homeostasis
      during cold stress. The muscle-specific promoter Smyd1 was used to express the
      carp muscle form III of creatine kinase (M3-CK), which maintained enzymatic
      activity at a relatively low temperature, in zebrafish skeletal muscle. In situ
      hybridization showed that M3-CK was expressed strongly in the skeletal muscle.
      When exposed to 13  degrees C, Tg (smyd1:m3ck) fish maintained their swimming
      behavior, while the wild-type could not. Energy measurements showed that the
      concentration of ATP increased in Tg (smyd1:m3ck) versus wild-type fish at 28 
      degrees C. After 2 h at 13  degrees C, ATP concentrations were 2.16-fold higher
      in Tg (smyd1:m3ck) than in wild-type (P<0.05). At 13  degrees C, the ATP
      concentration in Tg (smyd1:m3ck) fish and wild-type fish was 63.3% and 20.0%,
      respectively, of that in wild-type fish at 28  degrees C. Microarray analysis
      revealed differential expression of 1249 transcripts in Tg (smyd1:m3ck) versus
      wild-type fish under cold stress. Biological processes that were significantly
      overrepresented in this group included circadian rhythm, energy metabolism, lipid
      transport, and metabolism. These results are clues to understanding the
      mechanisms underlying temperature acclimation in fish.

PMID- 25058653
TI  - Risk factors and spatial distribution of Schistosoma mansoni infection among
      primary school children in Mbita District, Western Kenya.
AB  - BACKGROUND: An increasing risk of Schistosoma mansoni infection has been observed
      around Lake Victoria, western Kenya since the 1970s. Understanding local
      transmission dynamics of schistosomiasis is crucial in curtailing increased risk
      of infection. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a cross sectional
      study on a population of 310 children from eight primary schools. Overall, a
      total of 238 (76.8%) children were infected with S. mansoni, while seven (2.3%)
      had S. haematobium. The prevalence of hookworm, Trichuris trichiura and Ascaris
      lumbricoides were 6.1%, 5.2% and 2.3%, respectively. Plasmodium falciparum was
      the only malaria parasite detected (12.0%). High local population density within
      a 1 km radius around houses was identified as a major independent risk factor of
      S. mansoni infection. A spatial cluster of high infection risk was detected
      around the Mbita causeway following adjustment for population density and other
      potential risk factors. CONCLUSIONS/SIGNIFICANCE: Population density was shown to
      be a major factor fuelling schistosome infection while individual socio-economic
      factors appeared not to affect the infection risk. The high-risk cluster around
      the Mbita causeway may be explained by the construction of an artificial pathway
      that may cause increased numbers of S. mansoni host snails through obstruction of
      the waterway. This construction may have, therefore, a significant negative
      impact on the health of the local population, especially school-aged children who
      frequently come in contact with lake water.

PMID- 25058654
TI  - Effects of hatching time on behavior and weight development of chickens.
AB  - The length of the embryonic period varies both among and within species and can
      affect the individual phenotype in many ways, both physiologically and
      behaviorally. In chickens, the hatch window may last 24-48 hours (up to 10% of
      the incubation time), and studies have shown that incubation length may affect
      post-hatch growth and physiology. However, little is known about effects on
      behavior. We therefore investigated how behavior variation correlates with
      hatching time in the early life of chickens. We also measured egg weight and egg
      weight loss in relation to hatching time, as well as post-hatch growth. For
      females, there was a negative correlation between hatch time and body weight from
      day 4 and throughout the experiment. For males, such a correlation was only
      observed when testing all hatched males up until day 10. The birds were exposed
      to a number of behavioral tests, and a principal components analysis was
      performed on the variables, resulting in four components. For the largest
      component, termed "Passivity", a tendency of a difference was found between early
      and middle male hatchers. Furthermore, a significant difference between early and
      middle male hatchers was found in the second component, termed "Response to
      novelty". In a spatial learning test, late hatchers tended to learn slower. The
      behavior of females was not significantly affected by hatching time in any of
      these tests. This study is among the first to demonstrate a link between time of
      hatching and early behavior in a precocial species like the chicken, and may help
      shedding light on the evolutionary trade-offs between incubation length and post
      hatch traits. The results may also be relevant from a perspective of stress
      coping and therefore also for animal welfare and productivity in the chicken
      industry. The mechanisms linking hatching time with post-hatch phenotype remain
      to be investigated. 

PMID- 25058655
TI  - Using physiologically based pharmacokinetic (PBPK) modeling for dietary risk
      assessment of titanium dioxide (TiO2) nanoparticles.
AB  - Nano-sized titanium dioxide particles (nano-TiO2) can be found in a large number
      of foods and consumer products, such as cosmetics and toothpaste, thus, consumer
      exposure occurs via multiple sources, possibly involving different exposure
      routes. In order to determine the disposition of nano-TiO2 particles that are
      taken up, a physiologically based pharmacokinetic (PBPK) model was developed.
      High priority was placed on limiting the number of parameters to match the number
      of underlying data points (hence to avoid overparameterization), but still
      reflecting available mechanistic information on the toxicokinetics of nano-TiO2.
      To this end, the biodistribution of nano-TiO2 was modeled based on their ability
      to cross the capillary wall of the organs and to be phagocytosed in the
      mononuclear phagocyte system (MPS). The model's predictive power was evaluated by
      comparing simulated organ levels to experimentally assessed organ levels of
      independent in vivo studies. The results of our PBPK model indicate that: (1)
      within the application domain of the PBPK model from 15 to 150 nm, the size and
      crystalline structure of the particles had a minor influence on the
      biodistribution; and (2) at high internal exposure the particles agglomerate in
      vivo and are subsequently taken up by macrophages in the MPS. Furthermore, we
      also give an example on how the PBPK model may be used for risk assessment. For
      this purpose, the daily dietary intake of nano-TiO2 was calculated for the German
      population. The PBPK model was then used to convert this chronic external
      exposure into internal titanium levels for each organ.

PMID- 25058657
TI  - C60 fullerenol as an active and stable catalyst for the synthesis of cyclic
      carbonates from CO2 and epoxides.
AB  - C60 fullerenol was found to be a highly active, selective and stable catalyst for
      cycloaddition between CO2 and epoxides to produce various cyclic carbonates with
      excellent yields (89-99%). A solid/liquid interfacial hydrogen-bond assisted
      mechanism was proposed to account for its high efficiency. 

PMID- 25058656
TI  - Peripheral glia have a pivotal role in the initial response to axon degeneration
      of peripheral sensory neurons in zebrafish.
AB  - Axon degeneration is a feature of many peripheral neuropathies. Understanding the
      organismal response to this degeneration may aid in identifying new therapeutic
      targets for treatment. Using a transgenic zebrafish line expressing a bacterial
      nitroreductase (Ntr)/mCherry fusion protein in the peripheral sensory neurons of
      the V, VII, IX, and X cranial nerves, we were able to induce and visualize the
      pathology of axon degeneration in vivo. Exposure of 4 days post fertilization Ntr
      larvae to the prodrug metronidazole (Met), which Ntr metabolizes into cytotoxic
      metabolites, resulted in dose-dependent cell death and axon degeneration. This
      was limited to the Ntr-expressing sensory neurons, as neighboring glia and motor
      axons were unaffected. Cell death was rapid, becoming apparent 3-4 hours after
      Met treatment, and was followed by phagocytosis of soma and axon debris by cells
      within the nerves and ganglia beginning at 4-5 hours of exposure. Although
      neutrophils appear to be activated in response to the degenerating neurons, they
      did not accumulate at the sites of degeneration. In contrast, macrophages were
      found to be attracted to the sites of the degenerating axons, where they
      phagocytosed debris. We demonstrated that peripheral glia are critical for both
      the phagocytosis and inflammatory response to degenerating neurons: mutants that
      lack all peripheral glia (foxD3-/-; Ntr) exhibit a much reduced reaction to
      axonal degeneration, resulting in a dramatic decrease in the clearance of debris,
      and impaired macrophage recruitment. Overall, these results show that this
      zebrafish model of peripheral sensory axon degeneration exhibits many aspects
      common to peripheral neuropathies and that peripheral glia play an important role
      in the initial response to this process. 

PMID- 25058659
TI  - NO-binding in {Ru(NO)2}8-type [Ru(NO)2(PR3)2X]BF4 compounds.
AB  - Two different structure types were found for a series of mononuclear dinitrosyl
      complexes of the general formula [RuL2(NO)2X]BF4 (L = monodentate phosphane, X =
      Cl, Br, I). The {Ru(NO)2}(8)-type target compounds were prepared by the reduction
      of the respective {RuNO}(6) precursors and subsequent oxidative addition of
      (NO)BF4. About one half of the new compounds share their molecular structure with
      the hitherto only representative of this class of dinitrosyls, Pierpont and
      Eisenberg's [RuCl(NO)2(PPh3)2]PF6.C6H6 (Inorg. Chem., 1972, 11, 1088-1094). The
      Cs-symmetric cations exhibit both a linear and a bent Ru-N-O fragment, in line
      with a formal 6 + 2 split of the {Ru(NO)2}(8) electron sum in the sense of a
      [Ru(II)(NO(+))((1)NO(-))](2+) bonding. The coordination entity's configuration in
      this subgroup is described by IUPAC's polyhedral symbol SPY-5. Continuous shape
      measures (CShM) as defined by Alvarez et al. (Coord. Chem. Rev., 2005, 249, 1693
      1708) reveal a uniform deviation from the L-M-L angles expected for SPY-5, in a
      narrower sense, towards a vacant octahedron (vOC-5). DFT calculations confirmed
      that Enemark and Feltham's analysis (Coord. Chem. Rev., 1974, 13, 339-406) of the
      electronic situation of the {Ru(NO)2}(8) group remains adequate. The same holds
      for the second subclass of new compounds the existence of which had been
      predicted in the same paper by Enemark and Feltham, namely C(2v)-symmetric, TBPY
      5-type cations with two almost equally bonded nitrosyl ligands. In agreement with
      an 8 + 0 distribution of the relevant electrons, the formal [Ru(0)(NO(+))2](2+)
      entities are found for L/X couples that donate more electron density on the
      central metal. Two solid compounds (8a/b, 12a/b) were found in both structures
      including the special case of the P(i)Pr3/Br couple 12a/b, which led to crystals
      that contained both structure types in the same solid. Conversely, four compounds
      showed a single form in the solid but both forms in dichloromethane solution in
      terms of the solutions' IR spectra. The irradiation of crystalline 12 with blue
      laser light resulted in the photoisomerisation of, mainly, the bent (1)NO(-)
      ligand in terms of low-temperature IR spectroscopy.

PMID- 25058658
TI  - Abundance, composition and activity of ammonia oxidizer and denitrifier
      communities in metal polluted rice paddies from South China.
AB  - While microbial nitrogen transformations in soils had been known to be affected
      by heavy metal pollution, changes in abundance and community structure of the
      mediating microbial populations had been not yet well characterized in polluted
      rice soils. Here, by using the prevailing molecular fingerprinting and enzyme
      activity assays and comparisons to adjacent non-polluted soils, we examined
      changes in the abundance and activity of ammonia oxidizing and denitrifying
      communities of rice paddies in two sites with different metal accumulation
      situation under long-term pollution from metal mining and smelter activities.
      Potential nitrifying activity was significantly reduced in polluted paddies in
      both sites while potential denitrifying activity reduced only in the soils with
      high Cu accumulation up to 1300 mg kg-1. Copy numbers of amoA (AOA and AOB genes)
      were lower in both polluted paddies, following the trend with the enzyme assays,
      whereas that of nirK was not significantly affected. Analysis of the DGGE
      profiles revealed a shift in the community structure of AOA, and to a lesser
      extent, differences in the community structure of AOB and denitrifier between
      soils from the two sites with different pollution intensity and metal
      composition. All of the retrieved AOB sequences belonged to the genus
      Nitrosospira, among which species Cluster 4 appeared more sensitive to metal
      pollution. In contrast, nirK genes were widely distributed among different
      bacterial genera that were represented differentially between the polluted and
      unpolluted paddies. This could suggest either a possible non-specific target of
      the primers conventionally used in soil study or complex interactions between
      soil properties and metal contents on the observed community and activity
      changes, and thus on the N transformation in the polluted rice soils. 

PMID- 25058660
TI  - Negative density dependence regulates two tree species at later life stage in a
      temperate forest.
AB  - Numerous studies have demonstrated that tree survival is influenced by negative
      density dependence (NDD) and differences among species in shade tolerance could
      enhance coexistence via resource partitioning, but it is still unclear how NDD
      affects tree species with different shade-tolerance guilds at later life stages.
      In this study, we analyzed the spatial patterns for trees with dbh (diameter at
      breast height) >=2 cm using the pair-correlation g(r) function to test for NDD in
      a temperate forest in South Korea after removing the effects of habitat
      heterogeneity. The analyses were implemented for the most abundant shade-tolerant
      (Chamaecyparis obtusa) and shade-intolerant (Quercus serrata) species. We found
      NDD existed for both species at later life stages. We also found Quercus serrata
      experienced greater NDD compared with Chamaecyparis obtusa. This study indicates
      that NDD regulates the two abundant tree species at later life stages and it is
      important to consider variation in species' shade tolerance in NDD study. 

PMID- 25058661
TI  - A chemical switch for controlling viral infectivity.
AB  - Chemically triggered molecular switches for controlling the fate and function of
      biological systems are fundamental to the emergence of synthetic biology and the
      development of biomedical applications. We here present the first chemically
      triggered switch for controlling the infectivity of adeno-associated viral (AAV)
      vectors. 

PMID- 25058662
TI  - Parameter choice matters: validating probe parameters for use in mixed-solvent
      simulations.
AB  - Probe mapping is a common approach for identifying potential binding sites in
      structure-based drug design; however, it typically relies on energy minimizations
      of probes in the gas phase and a static protein structure. The mixed-solvent
      molecular dynamics (MixMD) approach was recently developed to account for full
      protein flexibility and solvation effects in hot-spot mapping. Our first study
      used only acetonitrile as a probe, and here, we have augmented the set of
      functional group probes through careful testing and parameter validation. A
      diverse range of probes are needed in order to map complex binding interactions.
      A small variation in probe parameters can adversely effect mixed-solvent
      behavior, which we highlight with isopropanol. We tested 11 solvents to identify
      six with appropriate behavior in TIP3P water to use as organic probes in the
      MixMD method. In addition to acetonitrile and isopropanol, we have identified
      acetone, N-methylacetamide, imidazole, and pyrimidine. These probe solvents will
      enable MixMD studies to recover hydrogen-bonding sites, hydrophobic pockets,
      protein-protein interactions, and aromatic hotspots. Also, we show that ternary
      solvent systems can be incorporated within a single simulation. Importantly,
      these binary and ternary solvents do not require artificial repulsion terms like
      other methods. Within merely 5 ns, layered solvent boxes become evenly mixed for
      soluble probes. We used radial distribution functions to evaluate solvent
      behavior, determine adequate mixing, and confirm the absence of phase separation.
      We recommend that radial distribution functions should be used to assess adequate
      sampling in all mixed-solvent techniques rather than the current practice of
      examining the solvent ratios at the edges of the solvent box. 

PMID- 25058663
TI  - Why did Swiss citizens refuse a comprehensive second-hand smoke ban?
AB  - The ill effects of second-hand smoke are now well documented. To protect the
      population from exposure to tobacco smoke, comprehensive smoking bans are
      necessary as expressed in the WHO Framework Convention on Tobacco Control and its
      guidelines. Switzerland has only a partial smoking ban full of exceptions which
      has been in effect since 2010, which reproduces the so-called Spanish model. In
      September 2012, the Swiss citizens refused a proposal for a more comprehensive
      ban. This case study examines the reasons behind this rejection and draws some
      lessons that can be learnt from it. 

PMID- 25058665
TI  - Strain accommodation by facile WO6 octahedral distortion and tilting during WO3
      heteroepitaxy on SrTiO3(001).
AB  - In this work, we demonstrate that WO6 octahedra in tungsten trioxide (WO3)
      undergo an unusually large degree of distortion and tilting to accommodate
      interfacial strain. This motion strongly impacts nucleation, structure, and
      defect formation during the epitaxial growth of WO3 on SrTiO3(001). A metastable
      tetragonal phase can be stabilized by heteroepitaxy and a thickness-dependent
      phase transition (tetragonal to monoclinic) is observed. In contrast to misfit
      dislocation formation, facile WO6 octahedral deformation gives rise to three
      types of planar defects. The thicknesses of affected regions can range from
      several to tens of nanometers with graded lattice parameters, allowing the strain
      from interfacial lattice mismatch to be relieved gradually. These atomically
      resolved, unique interfacial defects may significantly alter the electronic,
      electrochromic, and mechanical properties of WO3 epitaxial films. 

PMID- 25058664
TI  - Burden of diarrhea, hospitalization and mortality due to cryptosporidial
      infections in Indian children.
AB  - BACKGROUND: Cryptosporidium spp. is a common, but under-reported cause of
      childhood diarrhea throughout the world, especially in developing countries. A
      comprehensive estimate of the burden of cryptosporidiosis in resource-poor
      settings is not available. METHODOLOGY/PRINCIPAL FINDINGS: We used published and
      unpublished studies to estimate the burden of diarrhea, hospitalization and
      mortality due to cryptosporidial infections in Indian children. Our estimates
      suggest that annually, one in every 6-11 children <2 years of age will have an
      episode of cryptosporidial diarrhea, 1 in every 169-633 children will be
      hospitalized and 1 in every 2890-7247 children will die due to cryptosporidiosis.
      Since there are approximately 42 million children <2 years of age in India, it is
      estimated that Cryptosporidium results in 3.9-7.1 million diarrheal episodes,
      66.4-249.0 thousand hospitalizations, and 5.8-14.6 thousand deaths each year.
      CONCLUSIONS/SIGNIFICANCE: The findings of this study suggest a high burden of
      cryptosporidiosis among children <2 years of age in India and makes a compelling
      case for further research on transmission and prevention modalities of
      Cryptosporidium spp. in India and other developing countries.

PMID- 25058666
TI  - Eyelid myeloid sarcoma: ominous presentation of acute myelogenous leukemia.
AB  - A 19 year-old African American man presented to our clinic for a second opinion
      about a right upper eyelid mass which had been recalcitrant to treatment for
      nonspecific orbital inflammation by an outside facility. Examination for systemic
      causes of the patients eyelid lesion led to a diagnosis of acute myelogenous
      leukemia (AML) FAB subtype M1. A subsequent biopsy of the eyelid tumor confirmed
      the diagnosis of a myeloid sarcoma. The patient succumbed to complications from
      his leukemia within 13 months of presentation. This case report is the first, to
      our knowledge, of an eyelid myeloid sarcoma as the presenting sign of AML and
      demonstrates the poor prognosis of this lesion.

PMID- 25058667
TI  - Characterization of molybdenum monomeric oxide species supported on hydroxylated
      silica: a DFT study.
AB  - Periodic DFT calculations have been performed on molybdenum(VI) oxide species
      supported on the hydroxylated amorphous silica surface. The Mo grafting site has
      been investigated systematically for the type of silanol (geminate, vicinal,
      isolated or in a nest) accessible on the surface, as well as its effect on H-bond
      formation and stabilization, with the Mo-oxide species. Different grafting
      geometries, combined with different degrees of hydration of the Mo species are
      investigated using atomistic thermodynamics. The most stable Mo(VI) oxide species
      resulting from these calculations are confronted with experiment. Finally,
      calculated vibrational frequencies confirm the experimental evidence of the
      dominant presence of di grafted di-oxo Mo(VI) species on silica up to 700 K.

PMID- 25058668
TI  - Identification of related peptides through the analysis of fragment ion mass
      shifts.
AB  - Mass spectrometry (MS) has become the method of choice to identify and quantify
      proteins, typically by fragmenting peptides and inferring protein identification
      by reference to sequence databases. Well-established programs have largely solved
      the problem of identifying peptides in complex mixtures. However, to prevent the
      search space from becoming prohibitively large, most search engines need a list
      of expected modifications. Therefore, unexpected modifications limit both the
      identification of proteins and peptide-based quantification. We developed mass
      spectrometry-peak shift analysis (MS-PSA) to rapidly identify related spectra in
      large data sets without reference to databases or specified modifications.
      Peptide identifications from established tools, such as MASCOT or SEQUEST, may be
      propagated onto MS-PSA results. Modification of a peptide alters the mass of the
      precursor ion and some of the fragmentation ions. MS-PSA identifies
      characteristic fragmentation masses from MS/MS spectra. Related spectra are
      identified by pattern matching of unchanged and mass-shifted fragment ions. We
      illustrate the use of MS-PSA with simple and complex mixtures with both high and
      low mass accuracy data sets. MS-PSA is not limited to the analysis of peptides
      but can be used for the identification of related groups of spectra in any set of
      fragmentation patterns.

PMID- 25058669
TI  - Floral development at multiple spatial scales in Polygonum jucundum
      (Polygonaceae), a distylous species with broadly open flowers.
AB  - Distyly, a special polymorph, has evolved in many groups of angiosperms and has
      attracted attention since Darwin's time. Development studies on distylous taxa
      have helped us to understand the evolutionary process of this polymorph, but most
      of these studies focus on species with narrowly tubular corolla. Here, we studied
      the floral development of Polygonum jucundum, a distylous species with broadly
      open flowers, at multiple spatial scales. Results showed that the difference in
      stigma height between flowers of the two morphs was caused by differences in
      style growth throughout the entire floral development process. The observed
      difference in anther heights between the two morphs was because the filaments
      grew faster in short-styled (SS) than in long-styled (LS) flowers in the later
      stages of floral development. In addition, the longer styles in LS flowers than
      in SS flowers was because of faster cell division in the early stages of floral
      development. However, SS flowers had longer filaments than LS flowers primarily
      because of greater cell elongation. These results indicate that floral
      development in P. jucundum differs from that of distylous taxa with floral tubes
      shown in previous studies. Further, we conclude that the presence of distyly in
      species with open flowers is a result of convergent evolution. 

PMID- 25058670
TI  - Novel supramolecular elastomer films based on linear carboxyl-terminated
      polydimethylsiloxane oligomers: preparation, characterization, biocompatibility,
      and application in wound dressings.
AB  - A novel supramolecular elastomer (SESi) based on multiple hydrogen bond
      associations between low-molecular-weight polydimethylsiloxane chains was
      obtained through a two-step reaction of linear carboxyl-terminated
      polydimethylsiloxane oligomers with diethylenetriamine and urea, and the reaction
      mechanism was characterized. The results of differential scanning calorimetry and
      X-ray diffraction analyses indicated that the supramolecular network structure is
      completely amorphous, endowing SESi with rubber-like elastic behavior at room
      temperature. The transparent SESi film prepared by hot pressing displayed nice
      viscoelasticity, benign water absorption, water vapor transition rates, and ideal
      biocompatibility; and did not show cytotoxicity or skin irritation. These
      properties allow the elastomer to function as an occlusive wound dressing. To
      demonstrate its potential in wound dressings, a detailed comparison of commercial
      3M Tegaderm(TM) film and the SESi film was conducted. The SESi film exhibited
      similar effects in wound healing, and the wound bed was covered by the SESi film
      without the occurrence of significant adverse reactions. 

PMID- 25058671
TI  - The geography of diabetes by census tract in a large sample of insured adults in
      King County, Washington, 2005-2006.
AB  - INTRODUCTION: Identifying areas of high diabetes prevalence can have an impact on
      public health prevention and intervention programs. Local health practitioners
      and public health agencies lack small-area data on obesity and diabetes. METHODS:
      Clinical data from the Group Health Cooperative health care system were used to
      estimate diabetes prevalence among 59,767 adults by census tract. Area-based
      measures of socioeconomic status and the Modified Retail Food Environment Index
      were obtained at the census-tract level in King County, Washington. Spatial
      analyses and regression models were used to assess the relationship between
      census tract-level diabetes and area-based socioeconomic status and food
      environment variables. The mediating effect of obesity on the geographic
      distribution of diabetes was also examined. RESULTS: In this population of
      insured adults, diabetes was concentrated in south and southeast King County,
      with smoothed diabetes prevalence ranging from 6.9% to 21.2%. In spatial
      regression models, home value and college education were more strongly associated
      with diabetes than was household income. For each 50% increase in median home
      value, diabetes prevalence was 1.2 percentage points lower. The Modified Retail
      Food Environment Index was not related to diabetes at the census-tract level. The
      observed associations between area-based socioeconomic status and diabetes were
      largely mediated by obesity (home value, 58%; education, 47%). CONCLUSION: The
      observed geographic disparities in diabetes among insured adults by census tract
      point to the importance of area socioeconomic status. Small-area studies can help
      health professionals design community-based programs for diabetes prevention and
      control.

PMID- 25058672
TI  - Planning for the strategic recruitment of barbershops for blood pressure
      screening and referral in the Mississippi Delta region.

PMID- 25058673
TI  - Innovative and community-driven communication practices of the South Carolina
      cancer prevention and control research network.
AB  - The South Carolina Cancer Prevention and Control Research Network (SC-CPCRN) is 1
      of 10 networks funded by the Centers for Disease Control and Prevention and the
      National Cancer Institute (NCI) that works to reduce cancer-related health
      disparities. In partnership with federally qualified health centers and community
      stakeholders, the SC-CPCRN uses evidence-based approaches (eg, NCI Research
      tested Intervention Programs) to disseminate and implement cancer prevention and
      control messages, programs, and interventions. We describe the innovative
      stakeholder- and community-driven communication efforts conducted by the SC-CPCRN
      to improve overall health and reduce cancer-related health disparities among high
      risk and disparate populations in South Carolina. We describe how our
      communication efforts are aligned with 5 core values recommended for
      dissemination and implementation science: 1) rigor and relevance, 2) efficiency
      and speed, 3) collaboration, 4) improved capacity, and 5) cumulative knowledge. 

PMID- 25058674
TI  - Cancer prevention and worksite health promotion: time to join forces.

PMID- 25058675
TI  - An essential nonredundant role for mycobacterial DnaK in native protein folding.
AB  - Protein chaperones are essential in all domains of life to prevent and resolve
      protein misfolding during translation and proteotoxic stress. HSP70 family
      chaperones, including E. coli DnaK, function in stress induced protein refolding
      and degradation, but are dispensable for cellular viability due to redundant
      chaperone systems that prevent global nascent peptide insolubility. However, the
      function of HSP70 chaperones in mycobacteria, a genus that includes multiple
      human pathogens, has not been examined. We find that mycobacterial DnaK is
      essential for cell growth and required for native protein folding in
      Mycobacterium smegmatis. Loss of DnaK is accompanied by proteotoxic collapse
      characterized by the accumulation of insoluble newly synthesized proteins. DnaK
      is required for solubility of large multimodular lipid synthases, including the
      essential lipid synthase FASI, and DnaK loss is accompanied by disruption of
      membrane structure and increased cell permeability. Trigger Factor is
      nonessential and has a minor role in native protein folding that is only evident
      in the absence of DnaK. In unstressed cells, DnaK localizes to multiple, dynamic
      foci, but relocalizes to focal protein aggregates during stationary phase or upon
      expression of aggregating peptides. Mycobacterial cells restart cell growth after
      proteotoxic stress by isolating persistent DnaK containing protein aggregates
      away from daughter cells. These results reveal unanticipated essential
      nonredunant roles for mycobacterial DnaK in mycobacteria and indicate that DnaK
      defines a unique susceptibility point in the mycobacterial proteostasis network. 

PMID- 25058677
TI  - Molecular dynamics of the neuronal EF-hand Ca2+-sensor Caldendrin.
AB  - Caldendrin, L- and S-CaBP1 are CaM-like Ca2+-sensors with different N-termini
      that arise from alternative splicing of the Caldendrin/CaBP1 gene and that appear
      to play an important role in neuronal Ca2+-signaling. In this paper we show that
      Caldendrin is abundantly present in brain while the shorter splice isoforms L-
      and S-CaBP1 are not detectable at the protein level. Caldendrin binds both Ca2+
      and Mg2+ with a global Kd in the low uM range. Interestingly, the Mg2+-binding
      affinity is clearly higher than in S-CaBP1, suggesting that the extended N
      terminus might influence Mg2+-binding of the first EF-hand. Further evidence for
      intra- and intermolecular interactions of Caldendrin came from gel-filtration,
      surface plasmon resonance, dynamic light scattering and FRET assays.
      Surprisingly, Caldendrin exhibits very little change in surface hydrophobicity
      and secondary as well as tertiary structure upon Ca2+-binding to Mg2+-saturated
      protein. Complex inter- and intramolecular interactions that are regulated by
      Ca2+-binding, high Mg2+- and low Ca2+-binding affinity, a rigid first EF-hand
      domain and little conformational change upon titration with Ca2+ of Mg2+-liganted
      protein suggest different modes of binding to target interactions as compared to
      classical neuronal Ca2+-sensors. 

PMID- 25058679
TI  - Efficient synthesis of N-alkylated alpha,beta-unsaturated ketonitrones via Cu
      catalyzed rearrangement.
AB  - N-Alkylated unsaturated ketonitrones were efficiently synthesized from
      propargyloxyamines using Cu catalysts. Mechanistic studies suggest that the
      rearrangement reaction proceeds via Cu-catalyzed intramolecular hydroamination,
      followed by thermally induced electrocyclic ring opening. 

PMID- 25058678
TI  - Mung bean nuclease treatment increases capture specificity of microdroplet-PCR
      based targeted DNA enrichment.
AB  - Targeted DNA enrichment coupled with next generation sequencing has been
      increasingly used for interrogation of select sub-genomic regions at high depth
      of coverage in a cost effective manner. Specificity measured by on-target
      efficiency is a key performance metric for target enrichment. Non-specific
      capture leads to off-target reads, resulting in waste of sequencing throughput on
      irrelevant regions. Microdroplet-PCR allows simultaneous amplification of up to
      thousands of regions in the genome and is among the most commonly used strategies
      for target enrichment. Here we show that carryover of single-stranded template
      genomic DNA from microdroplet-PCR constitutes a major contributing factor for off
      target reads in the resultant libraries. Moreover, treatment of microdroplet-PCR
      enrichment products with a nuclease specific to single-stranded DNA alleviates
      off-target load and improves enrichment specificity. We propose that nuclease
      treatment of enrichment products should be incorporated in the workflow of
      targeted sequencing using microdroplet-PCR for target capture. These findings may
      have a broad impact on other PCR based applications for which removal of template
      DNA is beneficial. 

PMID- 25058680
TI  - Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals
      on virological suppression: 48-week efficacy and safety results.
AB  - OBJECTIVES: The objective of this study was to assess the 48-week virological
      efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two
      nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV
      RNA less than 50 copies/ml. METHODS: A multicentre, randomized, open-label,
      noninferiority trial. HIV-1 treated individuals on ATV/r 300/100 mg along with
      two NRTIs were randomized to receive ATV/r monotherapy or to maintain their
      antiretroviral regimen. The primary endpoint was the confirmed viral rebound
      (CVR: two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any
      reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs
      and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks
      since reintensification. RESULTS: One hundred and three patients enrolled. By
      week 48, 11 patients in ATV/r arm and two in ATV/r along with two NRTIs
      experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with
      two NRTIs discontinued. At the 48-week primary efficacy analysis (re
      intensification = failure), treatment success was 73% in ATV/r arm and 85% in
      ATV/r along with two NRTIs [difference -12.1%, 95% confidence interval (95% CI) 
      27.8 to 2.1]. According to the analysis considering re-intensification is equal
      to success, treatment success was 92% in ATV/r arm and 85% in the ATV/r along
      with two NRTIs arm (difference 7.5%, 95% CI -4.7 to 19.8). At CVR, no mutation
      was observed in ATV/r arm and reintensification with NRTIs was effective in all
      individuals. Overall, Grade 3-4 (P = 0.003) and grade 3-4 drug-related (P =
      0.027) adverse events were less frequent in ATV/r arm. A significant increase in
      total and low-density lipoprotein (LDL)-cholesterol was observed as well as a
      significant improvement in high-density lipoprotein (HDL)-cholesterol, fasting
      glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r
      monotherapy in comparison with ATV/r along with two NRTIs. CONCLUSION: ATV/r
      monotherapy treatment simplification showed lower virological efficacy in
      comparison with maintaining triple therapy; NRTIs reintroduction was effective in
      all the individuals.

PMID- 25058681
TI  - Depressed suicide attempters with posttraumatic stress disorder.
AB  - Posttraumatic stress disorder and major depressive disorder are well-established
      risk factors for suicidal behavior. This study compared depressed suicide
      attempters with and without comorbid posttraumatic stress disorder with respect
      to additional diagnoses, global functioning, depressive symptoms, substance
      abuse, history of traumatic exposure, and suicidal behavior. Adult patients
      consecutively admitted to a general hospital after a suicide attempt were
      interviewed and assessed for DSM-IV diagnosis and clinical correlates. Sixty-four
      patients (71%) were diagnosed with depression; of them, 21 patients (32%) had
      posttraumatic stress disorder. There were no group differences in social
      adjustment, depressive symptoms, or suicidal intent. However, the group with
      comorbid depression and posttraumatic stress disorder had more additional Axis I
      diagnoses, a higher degree of childhood trauma exposure, and more often reported
      previous suicide attempts, non-suicidal self-harm, and vengeful suicidal motives.
      These findings underline the clinical importance of diagnosis and treatment of
      posttraumatic stress disorder in suicide attempters. 

PMID- 25058682
TI  - Base-induced self-assembly for one-dimensional coordination polymers via chiral
      pendant-armed Schiff base mononuclear Pb(II) macrocycles.
AB  - A pair of 18-membered [1 + 1] chiral pendant-armed Schiff base macrocyclic
      mononuclear Pb(II) complexes with an unusual N1O2 coordination mode, synthesized
      from two chiral isomeric dialdehyde components, can be further self-assembled to
      one-dimensional ribbon coordination polymers by adding NaOH as a base to remove
      two phenolic protons. 

PMID- 25058684
TI  - Structure of the entire stalk region of the Dynein motor domain.
AB  - Dyneins are large microtubule-based motor complexes that power a range of
      cellular processes including the transport of organelles, as well as the beating
      of cilia and flagella. The motor domain is located within the dynein heavy chain
      and comprises an N-terminal mechanical linker element, a central ring of six AAA+
      modules of which four bind or hydrolyze ATP, and a long stalk extending from the
      AAA+ring with a microtubule-binding domain (MTBD) at its tip. A crucial mechanism
      underlying the motile activity of cytoskeletal motor proteins is precise coupling
      between the ATPase and track-binding activities. In dynein, a stalk region
      consisting of a long (~15nm) antiparallel coiled coil separates these two
      activities, which must facilitate communication between them. This communication
      is mediated by a small degree of helix sliding in the coiled coil. However, no
      high-resolution structure is available of the entire stalk region including the
      MTBD. Here, we have reported the structure of the entire stalk region of mouse
      cytoplasmic dynein in a weak microtubule-binding state, which was determined
      using X-ray crystallography, and have compared it with the dynein motor domain
      from Dictyostelium discoideum in a strong microtubule-binding state and with a
      mouse MTBD with its distal portion of the coiled coil fused to seryl-tRNA
      synthetase from Thermus thermophilus. Our results strongly support the helix
      sliding model based on the complete structure of the dynein stalk with a
      different form of coiled-coil packing. We also propose a plausible mechanism of
      helix sliding together with further analysis using molecular dynamics
      simulations. Our results present the importance of conserved proline residues for
      an elastic motion of stalk coiled coil and imply the manner of change between
      high-affinity state and low-affinity state of MTBD. 

PMID- 25058683
TI  - Diffusion of human replication protein A along single-stranded DNA.
AB  - Replication protein A (RPA) is a eukaryotic single-stranded DNA (ssDNA) binding
      protein that plays critical roles in most aspects of genome maintenance,
      including replication, recombination and repair. RPA binds ssDNA with high
      affinity, destabilizes DNA secondary structure and facilitates binding of other
      proteins to ssDNA. However, RPA must be removed from or redistributed along ssDNA
      during these processes. To probe the dynamics of RPA-DNA interactions, we
      combined ensemble and single-molecule fluorescence approaches to examine human
      RPA (hRPA) diffusion along ssDNA and find that an hRPA heterotrimer can diffuse
      rapidly along ssDNA. Diffusion of hRPA is functional in that it provides the
      mechanism by which hRPA can transiently disrupt DNA hairpins by diffusing in from
      ssDNA regions adjacent to the DNA hairpin. hRPA diffusion was also monitored by
      the fluctuations in fluorescence intensity of a Cy3 fluorophore attached to the
      end of ssDNA. Using a novel method to calibrate the Cy3 fluorescence intensity as
      a function of hRPA position on the ssDNA, we estimate a one-dimensional diffusion
      coefficient of hRPA on ssDNA of D1~5000nt(2) s(-1) at 37 degrees C. Diffusion of
      hRPA while bound to ssDNA enables it to be readily repositioned to allow other
      proteins access to ssDNA. 

PMID- 25058685
TI  - Cyclophilin-facilitated membrane translocation as pharmacological target to
      prevent intoxication of mammalian cells by binary clostridial actin ADP
      ribosylated toxins.
AB  - Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin and
      Clostridium difficile CDT belong to the family of binary actin ADP-ribosylating
      toxins and are composed of a binding/translocation component and a separate
      enzyme component. The enzyme components ADP-ribosylate G-actin in the cytosol of
      target cells resulting in depolymerization of F-actin, cell rounding and cell
      death. The binding/translocation components bind to their cell receptors and form
      complexes with the respective enzyme components. After receptor-mediated
      endocytosis, the binding/translocation components form pores in membranes of
      acidified endosomes and the enzyme components translocate through these pores
      into the cytosol. This step is facilitated by the host cell chaperone heat shock
      protein 90 and peptidyl-prolyl cis/trans isomerases including cyclophilin A.
      Here, we demonstrate that a large isoform of cyclophilin A, the multi-domain
      enzyme cyclophilin 40 (Cyp40), binds to the enzyme components C2I, Ia and CDTa in
      vitro. Isothermal titration calorimetry revealed a direct binding to C2I with a
      calculated affinity of 101 nM and to Ia with an affinity of 1.01 MUM. Closer
      investigation for the prototypic C2I revealed that binding to Cyp40 did not
      depend on its ADP-ribosyltransferase activity but was stronger for unfolded C2I.
      The interaction of C2I with Cyp40 was also demonstrated in lysates from C2
      treated cells by pull-down. Treatment of cells with a non-immunosuppressive
      cyclosporine A derivative, which still binds to and inhibits the peptidyl-prolyl
      cis/trans isomerase activity of cyclophilins, protected cells from intoxication
      with C2, iota and CDT toxins, offering an attractive approach for development of
      novel therapeutic strategies against binary actin ADP-ribosylating toxins.

PMID- 25058686
TI  - Presence of Helicobacter suis on pork carcasses.
AB  - Helicobacter (H.) suis is a world-wide spread pathogen which not only colonizes
      the stomach of pigs, but is also the most prevalent gastric non-H. pylori
      Helicobacter (NHPH) species in humans. H. suis infections are associated with
      gastric lesions both in pigs and in humans. Recently, the presence of viable H.
      suis bacteria has been demonstrated in minced pork, suggesting that manipulation
      or consumption of contaminated pig meat is a possible route of transmission of
      this zoonotic agent. The main goal of this study was to determine the extent of
      pork carcass contamination with H. suis at slaughter. In two consecutive studies,
      the occurrence of H. suis DNA was assessed in scalding water, head and mouth
      swabs, mesenteric lymph nodes, palatine tonsils and on the chest, shoulder and
      ham region of pork carcasses from three slaughterhouses using qPCR with ureA gene
      based H. suis-specific primers. H. suis DNA was detected on carcasses in all
      slaughterhouses, in 8.3% of all 1083 samples. It was found in all sampled
      matrices, except for the palatine tonsils and scalding water samples.
      Contamination levels of dressed pork samples did not exceed 184 genomic
      equivalents per 100cm(2) (shoulder, ham) or 300cm(2) (chest). All positive PCR
      products were subjected to sequence analysis of the ureA gene to confirm the
      identification of H. suis bacteria. Using multilocus sequence typing (MLST) on a
      selection of the positive samples, 5 unique sequence types (STs) could be
      assigned. Multiple H. suis strains were present on samples derived from one
      specific pig herd. Since H. suis DNA was detected in 11% (n: 90) of the
      mesenteric lymph nodes derived at the slaughterhouse, it was determined whether
      these organisms can colonize the mesenteric lymph nodes after experimental
      infection. Despite high-level colonization of the porcine stomachs with the H.
      suis strain, no H. suis DNA was detected in the mesenteric lymph nodes at four
      weeks after experimental infection. This might indicate that its presence in
      these tissues of slaughtered pigs is due to contamination during the slaughter
      process, but further studies are necessary to confirm this. In conclusion, we
      demonstrate a relatively high prevalence of H. suis on pork carcasses. 

PMID- 25058687
TI  - Inhibition of Campylobacter jejuni on fresh chicken breasts by kappa
      carrageenan/chitosan-based coatings containing allyl isothiocyanate or deodorized
      oriental mustard extract.
AB  - Campylobacter species are common bacterial pathogens associated with human
      gastroenteritis worldwide. The objectives of this study were to determine the
      minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations of allyl
      isothiocyanate (AITC) against 4 Campylobacter jejuni strains in Mueller-Hinton
      (MH) broth at 4, 21, 37 and 42 degrees C and to screen the C. jejuni strains for
      their ability to degrade sinigrin (which forms AITC) in pH7.0 MH broth at 35
      degrees C for 21d. Also evaluated was the antimicrobial activity of an edible
      0.2% kappa-carrageenan/2% chitosan-based coating containing AITC or deodorized
      oriental mustard extract against a 4 strain C. jejuni cocktail (6.2log10CFU/g) on
      vacuum-packaged fresh chicken breasts during 4 degrees C storage. MIC values of
      AITC were 0.63 to 1.25ppm and 2.5 to 5ppm against tested strains at 37 and 42
      degrees C, respectively. However, the MBC was 2.5 and 5ppm at 37 and 42 degrees
      C, respectively, and increased to a range of 40 to 160ppm at 4 degrees C. kappa
      Carrageenan/chitosan-based coatings containing 50 or 100MUl/g AITC reduced viable
      C. jejuni to undetectable levels on chicken breast after 5d at 4 degrees C, while
      25MUl/g AITC or 200 to 300mg/g mustard extract in coatings reduced C. jejuni
      numbers by 1.75 to 2.78log10CFU/g more than control coatings without
      antimicrobial. Both oriental mustard extract (50 to 300mg/g) and AITC (>=25MUl/g)
      reduced aerobic bacteria by 1.72 to 2.75log10CFU/g and lactic acid bacteria (LAB)
      by 0.94 to 3.36log10CFU/g by 21d compared to the control coating. kappa
      Carrageenan/chitosan coatings containing >=50MUl/g AITC or >=300mg/g oriental
      mustard showed excellent potential to control C. jejuni viability on raw chicken.

PMID- 25058688
TI  - Analysis of the erythroid differentiation effect of flavonoid apigenin on K562
      human chronic leukemia cells.
AB  - The erythroid differentiation-inducing effect of apigenin and its derivatives on
      human chronic myeloid leukemia K562 has been reported but the functional group in
      its structure responsible for the effect has not yet been elucidated. Here, we
      determined the moiety responsible for the erythroid differentiation induction
      effect of apigenin by using different flavonoids to represent the functional
      groups in its structure. In addition, we compared apigenin and apigetrin, a
      flavonoid similar in structure to apigenin except for the glycoside in its
      structure. Morphological changes as well as expressions of specific markers in
      K562 cells treated with apigenin were compared with those treated with apigetrin,
      flavone, 7-hydroxyflavone, chrysin, luteolin, or naringenin. The anti
      proliferative and erythroid differentiation-inducing effect of apigenin and the
      five flavonoids were then investigated and their effects on the alpha, beta, and
      gamma globin genes expressions were compared using real-time PCR. Results of the
      comparison between apigenin and apigetrin revealed that the glycoside part of
      apigetrin does not have a role in the induction of cell differentiation. Based on
      glycophorin A expression, the potency of the other flavonoids for induction of
      differentiation, was: apigenin>chrysin>flavone/7
      hydroxyflavone>luteolin/naringenin. Results of the analysis of the relationship
      between the structure and function of the flavonoids suggest that the apigenin
      induced K562 cell differentiation was due to the 2-3 double bond and hydroxyl
      groups in its structure. This is the first study that identified the specific
      functional group in apigenin that impact the erythroid differentiation effect in
      K562 cells. 

PMID- 25058689
TI  - Preterm birth in the first pregnancy and risk of neonatal death in the second
      pregnancy: a propensity score-weighted matching approach.
AB  - The study purpose was to assess the relationship between various grades of
      preterm birth (moderate preterm: 33-36 weeks; severe preterm: 27-32 weeks;
      extreme preterm: <= 26 weeks) in the first pregnancy and neonatal mortality
      (death within 28 days of birth; early: 0-7 days; late: 8-28 days) in the second
      pregnancy. Using the Missouri maternally-linked dataset (1989-2005), a population
      based, retrospective cohort analysis with propensity score-weighted matching was
      conducted on mothers with two consecutive singleton live births (n = 310,653
      women). Women with a prior preterm birth were more likely to subsequently
      experience neonatal death. The odds increased in a dose-dependent pattern with
      ascending severity of the preterm event in the first pregnancy (moderate preterm:
      AOR = 1.32; 95% CI: 1.10-1.60; severe preterm: AOR = 2.62; 95% CI: 2.01-3.41;
      extreme preterm: AOR = 5.84; 95% CI: 4.28-7.97; p value for trend < 0.001).
      However, the pathway for the relationship between prior preterm birth and
      subsequent neonatal mortality may be the recurrence of preterm birth.

PMID- 25058690
TI  - Heart failure in patients with human immunodeficiency virus: a review of the
      literature.
AB  - Coronary artery disease represents the leading cause of death for HIV patients
      treated with highly active antiretroviral treatment. Besides this, an extensive
      amount of data related to the risk of overt heart failure and consequently of
      atrial fibrillation and sudden cardiac death (SCD) in this population has been
      reported. It seems that persistent deregulation of immunity in HIV-infected
      patients is a common pathway related to both of these adverse clinical outcomes.
      Despite the fact that atrial fibrillation and heart failure are relatively common
      in HIV, few data are reported about screening, diagnosis, and potential treatment
      of these conditions. 

PMID- 25058691
TI  - Unguarded mitral orifice associated with hypoplastic left heart syndrome.
AB  - In the spectrum of mitral valve anomalies, unguarded mitral orifice is an
      exceedingly rare malformation, with only four cases described in the current
      literature. All previously reported cases have been associated with discordant
      atrioventricular connections. We describe the first known case of unguarded
      mitral valve orifice, in the setting of atrioventricular concordance, in a
      newborn with hypoplastic left heart syndrome. 

PMID- 25058693
TI  - Circadian rhythms - from genes to physiology and disease.
AB  - Most physiological processes in our body oscillate in a daily fashion. These
      include cerebral activity (sleep-wake cycles), metabolism and energy homeostasis,
      heart rate, blood pressure, body temperature, renal activity, and hormone as well
      as cytokine secretion. The daily rhythms in behaviour and physiology are not just
      acute responses to timing cues provided by the environment, but are driven by an
      endogenous circadian timing system. A central pacemaker in the suprachiasmatic
      nucleus (SCN), located in the ventral hypothalamus, coordinates all overt rhythms
      in our body through neuronal and humoral outputs. The SCN consists of two tiny
      clusters of ~100,000 neurones in humans, each harbouring a self-sustained, cell
      autonomous molecular oscillator. Research conducted during the past years has
      shown, however, that virtually all of our thirty-five trillion body cells possess
      their own clocks and that these are indistinguishable from those operative in SCN
      neurones. Here we give an overview on the molecular and cellular architecture of
      the mammalian circadian timing system and provide some thoughts on its medical
      and social impact. 

PMID- 25058692
TI  - Chromosomal aberrations in in-vitro matured oocytes influence implantation and
      ongoing pregnancy rates in a mouse model undergoing intracytoplasmic sperm
      injection.
AB  - Implantation failure and early pregnancy loss have been reported to be closely
      related to the quality of mammalian oocytes; however, the pregnant outcome of
      embryos from in-vitro matured (IVM) oocytes remains unknown. In this study we
      examined spindle assembly and chromosome segregation during differentiation, and
      the duration of IVM of mouse oocytes. The resulting implantation and pregnancy
      outcomes were analyzed to clarify the relationship between the spindle and
      chromosomes of IVM oocytes and implantation and early pregnancy. Cumulus-enclosed
      germinal vesicle oocytes were collected and randomly cultured in IVM medium with
      different IVM durations. One part of IVM oocytes were analyzed the spindle and
      chromosome morphology by immunofluorescence method, and the other part of them
      were fertilized by intracytoplasmic sperm injection. The resulting embryos were
      transferred into pseudo-pregnant female mice, and the post-implantation and full
      term development was observed. The chromosome aberrations and incorrect spindle
      assembly seems not affect the early development and blastocyst cell number
      derived from IVM oocytes, however the development potential of the resulting
      embryos after implantation were significant decreased with the ratio increasing
      of chromosome aberrations and incorrect spindle assembly. Accordingly, the full
      term development was also decreased. In conclusion, the present study showed the
      spindle assembly of in vitro-matured oocytes was one of the most important
      factors that affected the implantation and ongoing pregnancy rates of IVM
      oocytes, and the improvement by an appropriate duration of maturation in vitro
      will enhance the post-implantation development potential of the resulting
      embryos, and decrease implantation failure and early pregnancy loss. 

PMID- 25058694
TI  - Cardiovascular events and bleeding risk associated with intravitreal antivascular
      endothelial growth factor monoclonal antibodies: systematic review and meta
      analysis.
AB  - IMPORTANCE: Few data exist regarding the systemic safety of intravitreal
      antivascular endothelial growth factor (anti-VEGF) monoclonal antibody (mAb).
      OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the risk
      of major cardiovascular and nonocular hemorrhagic events in patients with
      neovascular age-related macular degeneration (AMD), diabetes mellitus-associated
      macular edema (DME), or retinal vein occlusions (RVOs) who receive intravitreal
      anti-VEGF mAbs. DATA SOURCES: The MEDLINE and Cochrane Central databases were
      searched for potentially eligible studies. STUDY SELECTION: Randomized clinical
      trials comparing ranibizumab or bevacizumab with no anti-VEGF treatment, as well
      as those comparing ranibizumab with bevacizumab in patients with AMD, DME, or
      RVOs. DATA EXTRACTION AND SYNTHESIS: We used a fixed-effects model and report the
      results as odds ratios (ORs) and 95% CIs. MAIN OUTCOMES AND MEASURES: Primary end
      points were major cardiovascular and nonocular hemorrhagic events. Secondary end
      points were all-cause mortality, cardiovascular mortality, stroke, myocardial
      infarction, venous thromboembolic events (VTEs), and hypertension. RESULTS:
      Twenty-one trials that evaluated 9557 patients were retrieved. Anti-VEGF mAbs did
      not significantly increase the risk of major cardiovascular events (OR, 1.18; 95%
      CI, 0.81-1.71) or nonocular hemorrhagic events (OR, 1.42; 95% CI, 0.95-2.13) in
      treatment groups compared with control populations. Bevacizumab did not increase
      the risk of major cardiovascular events (OR, 0.94; 95% CI, 0.59-1.52) or
      nonocular hemorrhagic events (OR, 2.56; 95% CI, 0.78-8.38) compared with
      ranibizumab, but significantly increased VTEs (OR, 3.45; 95% CI, 1.25-9.54).
      Subgroup analysis showed a significant increase of nonocular hemorrhagic events
      in patients with AMD in ranibizumab vs control trials (OR, 1.57; 95% CI, 1.01
      2.44). Anti-VEGF mAbs did not significantly increase overall mortality,
      cardiovascular mortality, stroke, myocardial infarction, VTEs, or hypertension.
      CONCLUSIONS AND RELEVANCE: We showed that intravitreal anti-VEGF-mAbs were not
      associated with significant increases in major cardiovascular or nonocular
      hemorrhagic events, but studies and meta-analyses were not powered enough to
      correctly assess these risks. Increased risks of VTEs with bevacizumab and
      nonocular hemorrhagic events in older patients with AMD with ranibizumab should
      be cautiously interpreted because more safety data are needed.

PMID- 25058695
TI  - Genome-wide identification and analysis of the aldehyde dehydrogenase (ALDH) gene
      superfamily of Gossypium raimondii.
AB  - BACKGROUND: Aldehyde dehydrogenases (ALDHs) are members of the NAD(P)(+)
      dependent protein superfamily which catalyzes aliphatic and aromatic aldehyde
      oxidation to non-toxic carboxylic acids. ALDH genes may offer promise for
      improving plant adaptation to environmental stress. Recently, elucidated genome
      sequences of Gossypium raimondii provide a foundation for systematic
      identification and analysis of ALDH genes. To date, this has been accomplished
      for many plant species except G. raimondii. RESULTS: In this study, thirty unique
      ALDH sequences that code for 10 ALDH families were identified in the G. raimondii
      genome. Phylogenetic analysis revealed that ALDHs were split into six clades in
      G. raimondii, and ALDH proteins from the same families were clustered together.
      Phylogenetic relationships of ALDHs from 11 plant species suggest that ALDHs in
      G. raimondii shared the highest protein homology with ALDHs from poplar. Members
      within ALDH families possessed homologous exon-intron structures. Chromosomal
      distribution of ALDH did not occur evenly in the G. raimondii genome and many
      ALDH genes were involved in the syntenic region as documented by identification
      of physical locations among single chromosomes. In addition, syntenic analysis
      revealed that homologues of many G. raimondii ALDHs appeared in corresponding
      Arabidopsis and poplar syntenic blocks, indicating that these genes arose prior
      to G. raimondii, Arabidopsis and poplar speciation. Finally, based on gene
      expression analysis of microarray and RNA-seq, we can speculate that some G.
      raimondii ALDH genes might respond to drought or waterlogging stresses.
      CONCLUSION: Genome-wide identification and analysis of the evolution and
      expression of ALDH genes in G. raimondii laid a foundation for studying this gene
      superfamily and offers new insights into the evolution history and speculated
      roles in Gossypium. These data can be used to inform functional genomic studies
      and molecular breeding in cotton.

PMID- 25058696
TI  - Complete mitochondrial genomes of five skippers (Lepidoptera: Hesperiidae) and
      phylogenetic reconstruction of Lepidoptera.
AB  - We sequenced mitogenomes of five skippers (family Hesperiidae, Lepidoptera) to
      obtain further insight into the characteristics of butterfly mitogenomes and
      performed phylogenetic reconstruction using all available gene sequences (PCGs,
      rRNAs, and tRNAs) from 85 species (20 families in eight superfamilies). The
      general genomic features found in the butterflies also were found in the five
      skippers: a high A+T composition (79.3%-80.9%), dominant usage of TAA stop codon,
      similar skewness pattern in both strands, consistently length intergenic spacer
      sequence between tRNA(Gln) and ND2 (64-87 bp), conserved ATACTAA motif between
      tRNA(Ser (UCN)) and ND1, and characteristic features of the A+T-rich region (the
      ATAGA motif, varying length of poly-T stretch, and poly-A stretch). The start
      codon for COI was CGA in four skippers as typical, but Lobocla bifasciatus
      evidently possessed canonical ATG as start codon. All species had the ancestral
      arrangement tRNA(Asn)/tRNA(Ser (AGN)), instead of the rearrangement tRNA(Ser
      (AGN))/tRNA(Asn), found in another skipper species (Erynnis). Phylogenetic
      analyses using all available genes (PCGs, rRNAS, and tRNAs) yielded the consensus
      superfamilial relationships
      ((((((Bombycoidea+Noctuoidea+Geometroidea)+Pyraloidea)+Papilionoidea)+Tortricoide
      )+Yponomeutoidea)+Hepialoidea), confirming the validity of Macroheterocera
      (Bombycoidea, Noctuoidea, and Geometroidea in this study) and its sister
      relationship to Pyraloidea. Within Rhopalocera (butterflies and skippers) the
      familial relationships
      (Papilionidae+(Hesperiidae+(Pieridae+((Lycaenidae+Riodinidae)+Nymphalidae))))
      were strongly supported in all analyses (0.98-1 by BI and 96-100 by ML methods),
      rendering invalid the superfamily status for Hesperioidea. On the other hand,
      current mitogenome-based phylogeny did not find consistent superfamilial
      relationships among Noctuoidea, Geometroidea, and Bombycoidea and the familial
      relationships within Bombycoidea between analyses, requiring further taxon
      sampling in future studies.

PMID- 25058697
TI  - Spine head calcium as a measure of summed postsynaptic activity for driving
      synaptic plasticity.
AB  - We use a computational model of a hippocampal CA1 pyramidal cell to demonstrate
      that spine head calcium provides an instantaneous readout at each synapse of the
      postsynaptic weighted sum of all presynaptic activity impinging on the cell. The
      form of the readout is equivalent to the functions of weighted, summed inputs
      used in neural network learning rules. Within a dendritic layer, peak spine head
      calcium levels are either a linear or sigmoidal function of the number of
      coactive synapses, with nonlinearity depending on the ability of voltage spread
      in the dendrites to reach calcium spike threshold. This is strongly controlled by
      the potassium A-type current, with calcium spikes and the consequent sigmoidal
      increase in peak spine head calcium present only when the A-channel density is
      low. Other membrane characteristics influence the gain of the relationship
      between peak calcium and the number of active synapses. In particular, increasing
      spine neck resistance increases the gain due to increased voltage responses to
      synaptic input in spine heads. Colocation of stimulated synapses on a single
      dendritic branch also increases the gain of the response. Input pathways
      cooperate: CA3 inputs to the proximal apical dendrites can strongly amplify peak
      calcium levels due to weak EC input to the distal dendrites, but not so strongly
      vice versa. CA3 inputs to the basal dendrites can boost calcium levels in the
      proximal apical dendrites, but the relative electrical compactness of the basal
      dendrites results in the reverse effect being less significant. These results
      give pointers as to how to better describe the contributions of pre- and
      postsynaptic activity in the learning "rules" that apply in these cells. The
      calcium signal is closer in form to the activity measures used in traditional
      neural network learning rules than to the spike times used in spike-timing
      dependent plasticity. 

PMID- 25058698
TI  - Learning rates of lq coefficient regularization learning with gaussian kernel.
AB  - Regularization is a well-recognized powerful strategy to improve the performance
      of a learning machine and l(q) regularization schemes with 0 < q < infinity are
      central in use. It is known that different q leads to different properties of the
      deduced estimators, say, l(2) regularization leads to a smooth estimator, while
      l(1) regularization leads to a sparse estimator. Then how the generalization
      capability of l(q) regularization learning varies with q is worthy of
      investigation. In this letter, we study this problem in the framework of
      statistical learning theory. Our main results show that implementing l(q)
      coefficient regularization schemes in the sample-dependent hypothesis space
      associated with a gaussian kernel can attain the same almost optimal learning
      rates for all 0 < q < infinity. That is, the upper and lower bounds of learning
      rates for l(q) regularization learning are asymptotically identical for all 0 < q
      < infinity. Our finding tentatively reveals that in some modeling contexts, the
      choice of q might not have a strong impact on the generalization capability. From
      this perspective, q can be arbitrarily specified, or specified merely by other
      nongeneralization criteria like smoothness, computational complexity or sparsity.

PMID- 25058699
TI  - On antiperiodic solutions for Cohen-Grossberg shunting inhibitory neural networks
      with time-varying delays and impulses.
AB  - In this letter, a class of Cohen-Grossberg shunting inhibitory neural networks
      with time-varying delays and impulses is investigated. Sufficient conditions for
      the existence and exponential stability of antiperiodic solutions of such a class
      of neural networks are established. Our results are new and complementary to
      previously known results. An example is given to illustrate the feasibility and
      effectiveness of our main results. 

PMID- 25058700
TI  - Design of charge-balanced time-optimal stimuli for spiking neuron oscillators.
AB  - In this letter, we investigate the fundamental limits on how the interspike time
      of a neuron oscillator can be perturbed by the application of a bounded external
      control input (a current stimulus) with zero net electric charge accumulation. We
      use phase models to study the dynamics of neurons and derive charge-balanced
      controls that achieve the minimum and maximum interspike times for a given bound
      on the control amplitude. Our derivation is valid for any arbitrary shape of the
      phase response curve and for any value of the given control amplitude bound. In
      addition, we characterize the change in the structures of the charge-balanced
      time-optimal controls with the allowable control amplitude. We demonstrate the
      applicability of the derived optimal control laws by applying them to
      mathematically ideal and experimentally observed neuron phase models, including
      the widely studied Hodgkin-Huxley phase model, and by verifying them with the
      corresponding original full state-space models. This work addresses a fundamental
      problem in the field of neural control and provides a theoretical investigation
      to the optimal control of oscillatory systems. 

PMID- 25058701
TI  - Extended robust support vector machine based on financial risk minimization.
AB  - Financial risk measures have been used recently in machine learning. For example,
      nu-support vector machine nu-SVM) minimizes the conditional value at risk (CVaR)
      of margin distribution. The measure is popular in finance because of the
      subadditivity property, but it is very sensitive to a few outliers in the tail of
      the distribution. We propose a new classification method, extended robust SVM (ER
      SVM), which minimizes an intermediate risk measure between the CVaR and value at
      risk (VaR) by expecting that the resulting model becomes less sensitive than nu
      SVM to outliers. We can regard ER-SVM as an extension of robust SVM, which uses a
      truncated hinge loss. Numerical experiments imply the ER-SVM's possibility of
      achieving a better prediction performance with proper parameter setting.

PMID- 25058703
TI  - Nonparametric estimation of Kullback-Leibler divergence.
AB  - In this letter, we introduce an estimator of Kullback-Leibler divergence based on
      two independent samples. We show that on any finite alphabet, this estimator has
      an exponentially decaying bias and that it is consistent and asymptotically
      normal. To explain the importance of this estimator, we provide a thorough
      analysis of the more standard plug-in estimator. We show that it is consistent
      and asymptotically normal, but with an infinite bias. Moreover, if we modify the
      plug-in estimator to remove the rare events that cause the bias to become
      infinite, the bias still decays at a rate no faster than O(1/n). Further, we
      extend our results to estimating the symmetrized Kullback-Leibler divergence. We
      conclude by providing simulation results, which show that the asymptotic
      properties of these estimators hold even for relatively small sample sizes.

PMID- 25058702
TI  - Efficient sensory encoding and Bayesian inference with heterogeneous neural
      populations.
AB  - The efficient coding hypothesis posits that sensory systems maximize information
      transmitted to the brain about the environment. We develop a precise and testable
      form of this hypothesis in the context of encoding a sensory variable with a
      population of noisy neurons, each characterized by a tuning curve. We
      parameterize the population with two continuous functions that control the
      density and amplitude of the tuning curves, assuming that the tuning widths vary
      inversely with the cell density. This parameterization allows us to solve, in
      closed form, for the information-maximizing allocation of tuning curves as a
      function of the prior probability distribution of sensory variables. For the
      optimal population, the cell density is proportional to the prior, such that more
      cells with narrower tuning are allocated to encode higher-probability stimuli and
      that each cell transmits an equal portion of the stimulus probability mass. We
      also compute the stimulus discrimination capabilities of a perceptual system that
      relies on this neural representation and find that the best achievable
      discrimination thresholds are inversely proportional to the sensory prior. We
      examine how the prior information that is implicitly encoded in the tuning curves
      of the optimal population may be used for perceptual inference and derive a novel
      decoder, the Bayesian population vector, that closely approximates a Bayesian
      least-squares estimator that has explicit access to the prior. Finally, we
      generalize these results to sigmoidal tuning curves, correlated neural
      variability, and a broader class of objective functions. These results provide a
      principled embedding of sensory prior information in neural populations and yield
      predictions that are readily testable with environmental, physiological, and
      perceptual data. 

PMID- 25058704
TI  - Visual motion priors differ for infants and mothers.
AB  - Visual motion direction ambiguities due to edge-aperture interaction might be
      resolved by speed priors, but scant empirical data support this hypothesis. We
      measured optic flow and gaze positions of walking mothers and the infants they
      carried. Empirically derived motion priors for infants are vertically elongated
      and shifted upward relative to mothers. Skewed normal distributions fitted to
      estimated retinal speeds peak at values above 20 degrees /sec.

PMID- 25058705
TI  - Fragility in dynamic networks: application to neural networks in the epileptic
      cortex.
AB  - Epilepsy is a network phenomenon characterized by atypical activity at the
      neuronal and population levels during seizures, including tonic spiking,
      increased heterogeneity in spiking rates, and synchronization. The etiology of
      epilepsy is unclear, but a common theme among proposed mechanisms is that
      structural connectivity between neurons is altered. It is hypothesized that
      epilepsy arises not from random changes in connectivity, but from specific
      structural changes to the most fragile nodes or neurons in the network. In this
      letter, the minimum energy perturbation on functional connectivity required to
      destabilize linear networks is derived. Perturbation results are then applied to
      a probabilistic nonlinear neural network model that operates at a stable fixed
      point. That is, if a small stimulus is applied to the network, the activation
      probabilities of each neuron respond transiently but eventually recover to their
      baseline values. When the perturbed network is destabilized, the activation
      probabilities shift to larger or smaller values or oscillate when a small
      stimulus is applied. Finally, the structural modifications to the neural network
      that achieve the functional perturbation are derived. Simulations of the
      unperturbed and perturbed networks qualitatively reflect neuronal activity
      observed in epilepsy patients, suggesting that the changes in network dynamics
      due to destabilizing perturbations, including the emergence of an unstable
      manifold or a stable limit cycle, may be indicative of neuronal or population
      dynamics during seizure. That is, the epileptic cortex is always on the brink of
      instability and minute changes in the synaptic weights associated with the most
      fragile node can suddenly destabilize the network to cause seizures. Finally, the
      theory developed here and its interpretation of epileptic networks enables the
      design of a straightforward feedback controller that first detects when the
      network has destabilized and then applies linear state feedback control to steer
      the network back to its stable state. 

PMID- 25058706
TI  - Hierarchical control using networks trained with higher-level forward models.
AB  - We propose and develop a hierarchical approach to network control of complex
      tasks. In this approach, a low-level controller directs the activity of a
      "plant," the system that performs the task. However, the low-level controller may
      be able to solve only fairly simple problems involving the plant. To accomplish
      more complex tasks, we introduce a higher-level controller that controls the
      lower-level controller. We use this system to direct an articulated truck to a
      specified location through an environment filled with static or moving obstacles.
      The final system consists of networks that have memorized associations between
      the sensory data they receive and the commands they issue. These networks are
      trained on a set of optimal associations generated by minimizing cost functions.
      Cost function minimization requires predicting the consequences of sequences of
      commands, which is achieved by constructing forward models, including a model of
      the lower-level controller. The forward models and cost minimization are used
      only during training, allowing the trained networks to respond rapidly. In
      general, the hierarchical approach can be extended to larger numbers of levels,
      dividing complex tasks into more manageable subtasks. The optimization procedure
      and the construction of the forward models and controllers can be performed in
      similar ways at each level of the hierarchy, which allows the system to be
      modified to perform other tasks or to be extended for more complex tasks without
      retraining lower-levels. 

PMID- 25058707
TI  - Dimensionality of object representations in monkey inferotemporal cortex.
AB  - We have calculated the intrinsic dimensionality of visual object representations
      in anterior inferotemporal (AIT) cortex, based on responses of a large sample of
      cells stimulated with photographs of diverse objects. Because dimensionality was
      dependent on data set size, we determined asymptotic dimensionality as both the
      number of neurons and number of stimulus image approached infinity. Our final
      dimensionality estimate was 93 (SD: +/- 11), indicating that there is basis set
      of approximately 100 independent features that characterize the dimensions of
      neural object space. We believe this is the first estimate of the dimensionality
      of neural visual representations based on single-cell neurophysiological data.
      The dimensionality of AIT object representations was much lower than the
      dimensionality of the stimuli. We suggest that there may be a gradual reduction
      in the dimensionality of object representations in neural populations going from
      retina to inferotemporal cortex as receptive fields become increasingly complex.

PMID- 25058708
TI  - Practice trends in patients with persistent detectable thyroglobulin and negative
      diagnostic radioiodine whole body scans: a survey of American Thyroid Association
      members.
AB  - BACKGROUND: Management of patients with thyroglobulin (Tg)-positive/scan-negative
      thyroid cancer remains challenging. American Thyroid Association (ATA) guidelines
      recommend potential use of empiric (131)I therapy and various scanning
      modalities, but no standard for managing such cases exists. METHODS: We surveyed
      ATA members to assess current practice in management of patients with Tg
      positive/scan-negative disease. Members participated in a web-based survey of six
      case scenarios of Tg elevations but iodine scan negativity. RESULTS: A total of
      288 ATA members (80% male) participated. Patient age, sex, and basal and
      stimulated Tg varied between the cases. Respondents were asked their opinion
      regarding empiric (131)I therapy use, including (131)I dose, use and duration of
      low-iodine diet, thyroxine withdrawal or recombinant human thyrotropin (rhTSH),
      and utilization of additional imaging (neck ultrasound (US) or positron emission
      tomography/computed tomography (PET/CT)) and reconsideration of (131)I therapy.
      Between 16% and 51% recommended initial use of empiric (131)I for the various
      scenarios. The majority chose a (131)I dose between 75 and 150 mCi, and 73%
      employed a low-iodine diet for two or more weeks. Preference between thyroxine
      withdrawal versus rhTSH was evenly split. More than 98% obtained a neck US if
      empiric (131)I was not given; 52-89% would proceed to PET/CT if US was negative.
      Only 44% used rhTSH stimulation in PET scan preparation. (131)I use was more
      common with stimulated Tg significantly >10 ng/mL. (131)I therapy was slightly
      more likely with PET-positive (56%) than PET-negative status (45%). Respondents
      were split regarding empiric (131)I if basal and stimulated Tg increased >=150%
      over two years. Providers in North America less commonly utilized (131)I
      treatment than those from other areas. In the face of possible heterophilic
      antibody interference in the Tg assay, the majority did not recommend (131)I
      therapy. CONCLUSIONS: Empiric (131)I therapy is still utilized for patients with
      Tg-positive/scan-negative disease. Neck US is frequently used to further evaluate
      such cases as (18)FDG-PET/CT, albeit the latter is used somewhat less often. Use
      of (131)I therapy correlated with the degree of Tg elevation or development of Tg
      antibodies, and was recommended more commonly with PET-positive than PET-negative
      status in patients with lower Tg levels. (131)I was less commonly used by
      providers within North America.

PMID- 25058709
TI  - A one-pot multicomponent coupling/cyclization for natural product herbicide (+/-)
      thaxtomin A.
AB  - Herbicide (+/-)-thaxtomin A has been synthesized in a one-pot process with a 32%
      isolated yield. A multicomponent coupling reaction was utilized to prepare in
      situ a dipeptide precursor which then sequentially underwent an alkaline mediated
      keto-amide cyclization to provide the target molecule. Adjustment of
      diastereoselectivity was achieved using microwave-induced irradiation. The
      approach incorporates atom economy and reaction efficiency and allows for facile
      library development. 

PMID- 25058716
TI  - Termination for fetal anomaly: are women in England given a choice of method?
AB  - Choice of a medical or surgical method of termination for fetal anomaly (TFA) is
      advocated in national guidelines based on a similar risk profile. We investigated
      whether women are offered a choice of method, by surveying members of a UK parent
      support organisation. An online questionnaire was designed to examine
      respondents' experience of TFA. A total of 351 responses were included in the
      final analysis. TFAs after 24 weeks' gestation and selective reductions were
      excluded. Mean gestational age at TFA was 17 weeks; 14% (n = 50) were offered a
      choice of method, falling to 8% (n = 19) after 14 weeks' gestation. Overall, 78%
      (n = 275) underwent medical TFA with 88% stating they chose it because it was the
      only method offered; 60% (n = 30) of those offered a choice had a surgical TFA.
      Our survey suggests that women having TFA are not offered a choice of method.
      Service delivery should be improved to meet national guidance and women's needs.

PMID- 25058718
TI  - Finding the evidence for clinical practice.

PMID- 25058717
TI  - To care, first, one must take care of oneself.

PMID- 25058721
TI  - Evaluation of discharge telephone calls following total joint replacement
      surgery.
AB  - The average length of stay for patients undergoing total joint replacement
      surgery at a large teaching hospital is 3 days. This requires a comprehensive
      discharge education plan. The purpose of this prospective quality improvement
      project was to evaluate patients' understanding of postoperative care at home,
      screen for postoperative complications, and identify inconsistencies or gaps in
      discharge teaching. During a 1-year evaluation period, patients who underwent
      total joint replacement surgery were interviewed via a telephone call following
      discharge to home. Patients were asked questions regarding general feeling, pain,
      wound appearance, edema, anticoagulation, and physical therapy. Concerns reported
      most frequently included medication side effects, deep vein thrombosis
      prophylaxis, and the use of assistive devices. The majority of patients reported
      receiving adequate discharge instructions. This quality improvement project has
      resulted in improved discharge teaching based on patients' identified needs and
      early intervention for the prevention of postoperative complications. 

PMID- 25058723
TI  - Plantar fasciitis: what is the diagnosis and treatment?
AB  - Foot pain, specifically plantar heel pain, is a common complaint among patients
      in a podiatric or orthopaedic office setting but may be seen in primary care
      offices, urgent care centers, or emergency departments as well. There are
      numerous causes for heel pain, but plantar fasciitis is the most frequent cause.
      The diagnosis of plantar fasciitis is generally made clinically, but there are
      many diagnostic modalities that may be used to confirm the diagnosis. Treatment
      of plantar fasciitis ranges from conservative measures to surgical interventions,
      but most cases of plantar fasciitis can be managed conservatively. There is no
      definitive treatment proven to be the best option for plantar fasciitis.
      Treatment is patient dependent and commonly requires a combination of different
      modalities to successfully alleviate the symptoms. In this article, plantar
      fasciitis from defining the disorder, diagnosis, and treatment are discussed. 

PMID- 25058725
TI  - A population-based survey of lumbar surgery beliefs in the United States.
AB  - INTRODUCTION: Studies have shown that lumbar surgery (LS) outcomes may be
      influenced by perception. However, the perceptions of the general population
      regarding LS are not known. Therefore, the purpose of this study was to
      investigate the general population's perceptions regarding LS. SUBJECTS: This
      study included 262 participants (mean age: 46.1 years; 125 males and 137 females)
      from the Las Vegas (NV) metropolitan area. METHODS: A questionnaire was developed
      by an expert panel and was assessed for face and content validity. After revision
      and establishment of test-retest reliability, participants were surveyed at 12
      randomly selected grocery stores in Las Vegas. The questionnaire assessed
      demographics, personal and family medical history, and 11 items pertaining to
      perceptions of LS. RESULTS: The participants had a somewhat uncertain expectation
      about the potential success of LS; however, approximately two-thirds believed
      that LS is unsuccessful to the point that they would not be able to return to
      their previous level of activity after LS. Of the questions dealing with success
      of LS, the neutral response had the greatest frequency suggesting a lack of
      knowledge or uncertainty about LS. More than half of the respondents were fearful
      of LS and anticipated a protracted recovery accompanied by undesired side
      effects. Three quarters of the respondents agreed that they would try all other
      means of treatment before opting for LS, yet 39% said that they would undergo LS
      if they had severe lower back pain (LBP). CONCLUSIONS: The general population has
      an uncertain view of LS outcomes and anticipates postoperative side effects and a
      protracted recovery; these views may explain why a majority of participants
      expressed fear of LS and why most would only opt for LS as a last resort. This
      uncertainty and anticipation of poor outcomes may be a strong contributor to
      preoperative fear and anxiety, which could deleteriously influence postoperative
      outcomes.

PMID- 25058727
TI  - The traditional method of oral as-needed pain medication delivery compared to an
      oral patient-controlled analgesia device following total knee arthroplasty.
AB  - As-needed (PRN) oral pain medication is an essential part of multimodal pain
      therapy. Medication delivery is often delayed because of multiple demands upon
      nursing time in a busy postoperative nursing unit. Postoperative pain control was
      compared using either the manual delivery of PRN oral pain medication or a
      bedside oral patient-controlled analgesia device. Thirty patients in each group
      completed a survey on the day of discharge, and additional data were collected by
      chart reviews. Device patients had significantly better pain scores than the
      usual care group on postoperative Day 2 and within the last 24 hours prior to
      discharge. The device group reported statistically less pain interference overall
      with general activity, mood, physical therapy, sleep, and appetite. Use of an
      oral patient-controlled analgesia device may improve pain management and patient
      function following total knee arthroplasty compared to the traditional delivery
      of oral PRN pain medication. 

PMID- 25058731
TI  - Nerve blocks for initial pain management of femoral fractures in children.
AB  - REVIEW QUESTION: What are the effects of nerve blocks (regional femoral
      anesthesia) on initial pain management in children with femoral fractures
      receiving prehospital or in-hospital emergency care, with or without systemic
      analgesia?

PMID- 25058729
TI  - Pain, opioids, and confusion after arthroplasty in older adults.
AB  - BACKGROUND: Postoperative confusion is a common complication in older adults,
      particularly after total joint replacement (arthroplasty). Confusion after
      surgery can result in slower mobility progression, longer hospital stay, and
      increased patient distress. Postoperative pain has been shown to be a risk factor
      related to confusion; however, there is limited evidence regarding pain level,
      medication use, and confusion development in postoperative arthroplasty patients.
      PURPOSE: To evaluate development of postoperative confusion and the current
      practice of pain management for older adult patients with hip or knee
      arthroplasty. METHODS: Two-month retrospective chart review of medical records at
      a large, Midwestern, private hospital. Pain assessments were performed on a
      regular basis using self-report 11-point Numeric Rating Scale (0-10). Opioid use
      was scored using an equianalgesic conversion chart. RESULTS: Ninety-eight
      patients met inclusion criteria and 97 received treatment with opioids during the
      first 48 hours postoperatively. No patients received opioid agents that are
      contraindicated in older adults. Thirty-three patients had evidence in the
      medical record of confusion during the first 48 hours postoperatively. Lower
      equianalgesic dose was significant for increased age and increased confusion on
      postoperative day 1 (POD 1) and POD 2. Patients with higher equianalgesic scores
      were less likely to meet benchmark pain scores less than 5 on POD 0, POD 1, and
      POD 2. CONCLUSIONS: Patients receiving lower amounts of opioids in the first 48
      hours after surgery were more likely to be confused on POD 1(p = .023) and POD 2
      (p = .049).

PMID- 25058734
TI  - A critical-sized bone defect.

PMID- 25058733
TI  - Monitoring antigenic variations of enterovirus 71: implications for virus
      surveillance and vaccine development.
AB  - Enterovirus 71 (EV71) causes life-threatening epidemics in Asia and can be
      phylogenetically classified into three major genogroups (A ~ C) including 11
      genotypes (A, B1 ~ B5, and C1 ~ C5). Recently, EV71 epidemics occurred cyclically
      in Taiwan with different genotypes. In recent years, human studies using post
      infection sera obtained from children have detected antigenic variations among
      different EV71 strains. Therefore, surveillance of enterovirus 71 should include
      phylogenetic and antigenic analysis. Due to limitation of sera available from
      children with EV71 primary infection, suitable animal models should be developed
      to generate a panel of antisera for monitoring EV71 antigenic variations. Twelve
      reference strains representing the 11 EV71 genotypes were grown in
      rhabdomyosarcoma cells. Infectious EV71 particles were purified and collected to
      immunize rabbits. The rabbit antisera were then employed to measure neutralizing
      antibody titers against the 12 reference strains and 5 recent strains. Rabbits
      immunized with genogroup B and C viruses consistently have a lower neutralizing
      antibody titers against genogroup A (? 8-fold difference) and antigenic
      variations between genogroup B and C viruses can be detected but did not have a
      clear pattern, which are consistent with previous human studies. Comparison
      between human and rabbit neutralizing antibody profiles, the results showed that
      ? 8-fold difference in rabbit cross-reactive antibody ratios could be used to
      screen EV71 isolates for identifying potential antigenic variants. In conclusion,
      a rabbit model was developed to monitor antigenic variations of EV71, which are
      critical to select vaccine strains and predict epidemics.

PMID- 25058735
TI  - Error-correction learning for artificial neural networks using the Bayesian
      paradigm. Application to automated medical diagnosis.
AB  - Automated medical diagnosis models are now ubiquitous, and research for
      developing new ones is constantly growing. They play an important role in medical
      decision-making, helping physicians to provide a fast and accurate diagnosis. Due
      to their adaptive learning and nonlinear mapping properties, the artificial
      neural networks are widely used to support the human decision capabilities,
      avoiding variability in practice and errors based on lack of experience. Among
      the most common learning approaches, one can mention either the classical back
      propagation algorithm based on the partial derivatives of the error function with
      respect to the weights, or the Bayesian learning method based on posterior
      probability distribution of weights, given training data. This paper proposes a
      novel training technique gathering together the error-correction learning, the
      posterior probability distribution of weights given the error function, and the
      Goodman-Kruskal Gamma rank correlation to assembly them in a Bayesian learning
      strategy. This study had two main purposes; firstly, to develop anovel learning
      technique based on both the Bayesian paradigm and the error back-propagation, and
      secondly,to assess its effectiveness. The proposed model performance is compared
      with those obtained by traditional machine learning algorithms using real-life
      breast and lung cancer, diabetes, and heart attack medical databases. Overall,
      the statistical comparison results indicate that thenovellearning approach
      outperforms the conventional techniques in almost all respects. 

PMID- 25058736
TI  - Inorganic particles increase biofilm heterogeneity and enhance permeate flux.
AB  - This study investigated the influence of inorganic particles on the hydraulic
      resistance of biofilm grown on membrane surface during low-pressure dead-end
      ultrafiltration. Gravity-driven ultrafiltration membrane systems were operated
      during several weeks without any flushing or cleaning. Smaller (kaolin d0.5 = 3.6
      MUm) or larger (kaolin with diatomaceous earth 50/50%, d0.5 = 18.1 MUm) particles
      were added to pre-filtered creek water or to unfiltered creek water. It was
      demonstrated in both experiments that presence of finer particles in the feed
      water (kaolin) induced formation of compact and homogeneous biofilm structure. On
      the other hand presence of the larger particles (diatomite) helped to
      counterbalance the effect of fine particles due to the formation of more
      heterogeneous and permeable biofilm structure. The hydraulic resistance of
      biofilms formed with fine particles was significantly higher than the resistance
      of biofilm formed in (1) absence of any inorganic particles or (2) in presence of
      the mixed particle population. The membrane orientation (vertical or horizontal)
      determined which particles were accumulating at the membrane surface, with
      structural differences shown by Scanning Electron Microscopy (SEM). For vertical
      membranes, the larger particles were selectively removed due to sedimentation and
      did not contribute to the biofilm development. Thus the selection of smaller
      particles due to vertical membrane configuration negatively affected the biofilm
      structure and permeation rates, and such selective accumulation of fine particles
      should be avoided. 

PMID- 25058737
TI  - Accurate and self-consistent procedure for determining pH in seawater
      desalination brines and its manifestation in reverse osmosis modeling.
AB  - Measuring and modeling pH in concentrated aqueous solutions in an accurate and
      consistent manner is of paramount importance to many R&D and industrial
      applications, including RO desalination. Nevertheless, unified definitions and
      standard procedures have yet to be developed for solutions with ionic strength
      higher than ~0.7 M, while implementation of conventional pH determination
      approaches may lead to significant errors. In this work a systematic yet simple
      methodology for measuring pH in concentrated solutions (dominated by Na(+)/Cl(-))
      was developed and evaluated, with the aim of achieving consistency with the
      Pitzer ion-interaction approach. Results indicate that the addition of 0.75 M of
      NaCl to NIST buffers, followed by assigning a new standard pH (calculated based
      on the Pitzer approach), enabled reducing measured errors to below 0.03 pH units
      in seawater RO brines (ionic strength up to 2 M). To facilitate its use, the
      method was developed to be both conceptually and practically analogous to the
      conventional pH measurement procedure. The method was used to measure the pH of
      seawater RO retentates obtained at varying recovery ratios. The results matched
      better the pH values predicted by an accurate RO transport model. Calibrating the
      model by the measured pH values enabled better boron transport prediction. A
      Donnan-induced phenomenon, affecting pH in both retentate and permeate streams,
      was identified and quantified. 

PMID- 25058738
TI  - Total and state-specific medical and absenteeism costs of COPD among adults aged
      >= 18 years in the United States for 2010 and projections through 2020.
AB  - BACKGROUND: COPD remains a leading cause of morbidity and mortality. The
      objectives of this study were to estimate (1) national US COPD-attributable
      annual medical costs by payer (direct) and absenteeism (indirect) in 2010 and
      projected medical costs through 2020 and (2) state-specific COPD-attributable
      medical and absenteeism costs in 2010. METHODS: We used the 2006-2010 Medical
      Expenditure Panel Survey, the 2004 National Nursing Home Survey, and 2010 Centers
      for Medicare and Medicaid Services data to generate cost estimates and 2010
      census data to project medical costs through 2020. RESULTS: In 2010, total
      national medical costs attributable to COPD and its sequelae were estimated at
      $32.1 billion, and total absenteeism costs were $3.9 billion, for a total burden
      of COPD-attributable costs of $36 billion. An estimated 16.4 million days of work
      were lost because of COPD. Of the medical costs, 18% was paid for by private
      insurance, 51% by Medicare, and 25% by Medicaid. National medical costs are
      projected to increase from $32.1 billion in 2010 to $49.0 billion in 2020. Total
      state-specific costs in 2010 ranged from $49.1 million in Wyoming to $2.8 billion
      in California: medical costs ranged from $42.5 million in Alaska to $2.5 billion
      in Florida and absenteeism costs ranged from $8.4 million in Wyoming to $434.0
      million in California. CONCLUSIONS: Costs attributable to COPD and its sequelae
      are substantial and are projected to increase through 2020. Evidence-based
      interventions that prevent tobacco use and reduce the clinical complications of
      COPD may result in potential decreased COPD-attributable costs.

PMID- 25058739
TI  - Polyelectrolyte assisted synthesis and enhanced oxygen reduction activity of Pt
      nanocrystals with controllable shape and size.
AB  - The shape control of platinum nanocrystals is significant to the enhancement of
      their catalytic performance in terms of activity and selectivity. However, it
      still remains a major challenge to prepare Pt nanocrystals with tunable shape and
      clean surface in an eco-friendly way. This article develops a facile and green
      strategy to prepare well tuned platinum nanocrystals employing
      poly(diallyldimethylammonium chloride) (PDDA) as the capping agent, reductant,
      and stabilizer simultaneously in a facile hydrothermal process. It is identified
      that the variation of PDDA concentration is crucial to control the growth of
      crystalline facets, leading to the formation of cubic, truncated cubic, and
      octahedral Pt nanocrystals with sizes tunable from ca. 17 nm to ca. 50 nm. The
      resultant Pt nanocrystals exhibit excellent electrocatalytic activity and
      stability toward the oxygen reduction reaction (ORR) in acidic media compared
      with those of commercial Pt black and the state-of-the-art Pt/C catalyst. It is
      proposed that the preferential Pt surface and the decoration of PDDA, which
      modulates the electronic structures and electrooxidation of Pt nanocrystals,
      synergistically contribute to the enhanced catalytic performance. 

PMID- 25058746
TI  - Critical congenital heart disease screening by pulse oximetry in a neonatal
      intensive care unit.
AB  - OBJECTIVE: Critical congenital heart disease (CCHD) screening is effective in
      asymptomatic late preterm and term newborn infants with a low false-positive rate
      (0.035%). (1) To compare 2817 neonatal intensive care unit (NICU) discharges
      before and after implementation of CCHD screening; and (2) to evaluate CCHD
      screening at <35 weeks gestation. STUDY DESIGN: Collection of results of CCHD
      screening including pre- and postductal pulse oximetry oxygen saturation (SpO2)
      values. RESULT: During the pre-CCHD screen period, 1247 infants were discharged
      from the NICU and one case of CCHD was missed. After 1 March 2012, 1508 CCHD
      screens were performed among 1570 discharges and no CCHDs were missed. The pre-
      and postductal SpO2 values were 98.8 +/- 1.4% and 99 +/- 1.3%, respectively, in
      preterm and 98.9 +/- 1.3% and 98.9 +/- 1.4%, respectively, in term infants. Ten
      infants had false-positive screens (10/1508 = 0.66%). CONCLUSION: Performing
      universal screening in the NICU is feasible but is associated with a higher false
      positive rate compared with asymptomatic newborn infants.

PMID- 25058745
TI  - Sex differences in the neurobiology of epilepsy: a preclinical perspective.
AB  - When all of the epilepsies are considered, sex differences are not always clear,
      despite the fact that many sex differences are known in the normal brain. Sex
      differences in epilepsy in laboratory animals are also unclear, although robust
      effects of sex on seizures have been reported, and numerous effects of gonadal
      steroids have been shown throughout the rodent brain. Here we discuss several
      reasons why sex differences in seizure susceptibility are unclear or are
      difficult to study. Examples of robust sex differences in laboratory rats, such
      as the relative resistance of adult female rats to the chemoconvulsant
      pilocarpine compared to males, are described. We also describe a novel method
      that has shed light on sex differences in neuropathology, which is a relatively
      new technique that will potentially contribute to sex differences research in the
      future. The assay we highlight uses the neuronal nuclear antigen NeuN to probe
      sex differences in adult male and female rats and mice. In females, weak NeuN
      expression defines a sex difference that previous neuropathological studies have
      not described. We also show that in adult rats, social isolation stress can
      obscure the normal effects of 17beta-estradiol to increase excitability in area
      CA3 of the hippocampus. These data underscore the importance of controlling
      behavioral stress in studies of seizure susceptibility in rodents and suggest
      that behavioral stress may be one factor that has led to inconsistencies in
      outcomes of sex differences research. These and other issues have made it
      difficult to translate our increasing knowledge about the effects of gonadal
      hormones on the brain to improved treatment for men and women with epilepsy.

PMID- 25058747
TI  - Maternal anti-D prophylaxis during pregnancy and risk of hemolysis among preterm
      infants.
AB  - OBJECTIVE: To evaluate whether Rh-positive preterm newborn infants born to Rh
      negative mothers treated with prophylactic anti-D immunoglobulins exhibited signs
      of hemolytic reaction, including anemia and hyperbilirubinemia. STUDY DESIGN:
      Retrospective data were collected for 94 Rh-positive preterm newborns born at
      gestational age (GA) 28 to 34 weeks to 76 Rh-negative mothers and for matched
      controls. RESULT: We found 11.7% positive Coombs' tests among infants in the
      study group and slightly higher bilirubin levels at birth and on the following 3
      days. No differences were recorded between the study and the control groups for
      hematocrit levels throughout hospitalization, maximal bilirubin level,
      phototherapy treatment or the need for blood transfusion. CONCLUSION: Among
      preterm Rh-positive newborn infants born to Rh-negative mothers, there appears to
      be no evidence of significant hemolytic reaction derived from placental anti-D
      transfer. Further prospective studies are needed to confirm these findings in
      order to support anti-D administration close to preterm birth.

PMID- 25058748
TI  - Standardizing morphine use for ventilated preterm neonates with a nursing-driven
      comfort protocol.
AB  - OBJECTIVE: To test whether implementing a nursing-driven comfort protocol
      standardizes morphine use in one neonatal intensive care unit (NICU) and to
      examine how non-standard morphine (N-SM) relates to days of ventilation, days of
      total parenteral nutrition (TPN) and length of stay (LOS). STUDY DESIGN: This was
      a retrospective/prospective observational study using pharmacy records, medical
      records, and an outcomes database. Comfort protocol implementation began February
      2011 and was applied to preterm, ventilated neonates <1500 grams. Pre- and post
      implementation proportions of N-SM days were compared using the binomial test. A
      percent 'P'-chart spanning 30 quarters was constructed with statistical-process
      control analysis. Multivariable linear regression adjusting for acuity assessed
      the relationship between N-SM use and days of ventilation, TPN and LOS. RESULT:
      Hundred and thirty-four patients met inclusion criteria, 116 prior to and 18
      after implementation. The proportion of patients given N-SM for one or more days
      decreased from 59 to 35% after protocol implementation (P = 0.017). A 9-month
      period of decreased N-SM days was observed after protocol implementation.
      Controlling for acuity, each additional day of N-SM use was associated with 0.47
      more days of ventilation (95% confidence interval (CI): 0.26-0.69, P < 0.001) and
      0.52 more days of TPN (95% CI: 0.35-0.68, P < 0.001). Exposure to N-SM was
      associated with 17 additional days of hospitalization (P = 0.009, 95% CI: 4.5
      30). CONCLUSION: Implementing a nursing-driven comfort protocol significantly
      reduced N-SM use. N-SM in the NICU is negatively associated with key clinical
      outcomes. Testing similar protocols in other settings is warranted.

PMID- 25058749
TI  - Isolation of a uranium(III) benzophenone ketyl radical that displays redox-active
      ligand behaviour.
AB  - The first uranium(III) charge separated ketyl radical complex, Tp*2U(OC.Ph2), has
      been isolated and characterized by infrared, (1)H NMR, and electronic absorption
      spectroscopies, along with X-ray crystallography. Tp*2U(OC.Ph2) is a potent two
      electron reductant towards N3Mes (Mes = 2,4,6-trimethylphenyl) and (2,2,6,6
      tetramethyl-piperidin-1-yl)oxyl (TEMPO), with reducing equivalents derived from
      the metal centre and the redox-active benzophenone.

PMID- 25058750
TI  - Mechanical stretch induces lung alpha-epithelial Na(+) channel expression.
AB  - ABSTRACT During fetal development physiological stretching helps drive lung
      growth and maturation. At birth, the alpha-subunit of the alveolar epithelial
      sodium channel (alpha-ENaC) is a critical factor in helping to facilitate
      clearance of lung fluid during the perinatal period. The effects of stretch,
      however, on alpha-ENaC expression in the fetal lung have yet to be elucidated. In
      an effort to explore this question, we used both an in vitro cell culture model
      that exposes cells to repetitive cyclic stretch (CS) as well as an in vivo
      preterm animal model of mechanical ventilation (MV). We found that murine lung
      epithelial (MLE-12) cells exposed to repetitive CS showed a significant rise in
      alpha-ENaC mRNA expression. Total and cell-surface protein abundance of alpha
      ENaC were also elevated after 24 h of CS. Stretch-induced increases in alpha-ENaC
      expression were suppressed in the presence of either actinomycin D or
      cycloheximide. Pharmacological inhibition of the extracellular signal-regulated
      protein kinase (ERK1/2) did not attenuate stretch-induced increases in alpha-ENaC
      protein, whereas inhibition of p38 MAPK or c-Jun NH2-terminal kinase (JNK) did.
      In 29-day preterm rabbits, alveolar stretching secondary to postnatal MV markedly
      elevated fetal lung alpha-ENaC expression compared to spontaneously breathing
      counterparts. In summary, our findings indicate that mechanical stretch promotes
      alpha-ENaC expression. 

PMID- 25058751
TI  - Exploring vertex interactions in ferroelectric flux-closure domains.
AB  - Using piezoresponse force microscopy, we have observed the progressive
      development of ferroelectric flux-closure domain structures and Landau-Kittel
      type domain patterns, in 300 nm thick single-crystal BaTiO3 platelets. As the
      microstructural development proceeds, the rate of change of the domain
      configuration is seen to decrease exponentially. Nevertheless, domain wall
      velocities throughout are commensurate with creep processes in oxide
      ferroelectrics. Progressive screening of macroscopic destabilizing fields,
      primarily the surface-related depolarizing field, successfully describes the main
      features of the observed kinetics. Changes in the separation of domain-wall
      vertex junctions prompt a consideration that vertex-vertex interactions could be
      influencing the measured kinetics. However, the expected dynamic signatures
      associated with direct vertex-vertex interactions are not resolved. If present,
      our measurements confine the length scale for interaction between vertices to the
      order of a few hundred nanometers. 

PMID- 25058752
TI  - Characterization of a highly thermostable glycoside hydrolase family 10 xylanase
      from Malbranchea cinnamomea.
AB  - A thermostable xylanase (McXyn10) from the thermophilic fungus Malbranchea
      cinnamomea strain S168 was purified and biochemically characterized. The enzyme
      was purified to homogeneity with a molecular mass of 43.5 kDa on SDS-PAGE. The
      optimal pH and temperature of the purified enzyme were pH 6.5 and 80 degrees C,
      respectively. The enzyme showed a broad range of pH stability (pH 4.0-10.5), and
      was stable up to 70 degrees C with a thermal denaturing half life of 76.0 min.
      The enzyme exhibited strict specificity for various xylans as substrates, but
      displayed no activity toward other tested polysaccharides. McXyn10 hydrolyzed
      birchwood xylan, beechwood xylan and oat-spelt xylan, yielded mainly xylobiose,
      xylotriose and xylooligosaccharides with degree of polymerization (DP) above 5,
      while yielded xylobiose from xylotriose and xylotetraose. The xylanase gene was
      further cloned. It had an open reading frame of 1191 bp with two introns. The
      deduced amino acid sequence of the gene showed highest identity (58%) with a
      glycoside hydrolase family 10 xylanase from Aureobasidium pullulans.

PMID- 25058753
TI  - Pectin from Abelmoschus esculentus: optimization of extraction and rheological
      properties.
AB  - Response surface methodology (RSM) was applied to optimize the parameters of
      pectin extraction from okra pods. The extracted okra pectin was then investigated
      by steady-shear and oscillatory rheological measurements. Statistical analysis
      showed that the linear term of the liquid-solid ratio, the quadratic term of the
      pH, and the linear term of the extraction time showed highly significant effects
      on pectin yield. The optimal extraction conditions that maximized the pectin
      yield within the experimental range of the variables researched were a pH of 3.9,
      an extraction time of 64 min, an extraction temperature of 60 degrees C, and a
      liquid-solid ratio of 42:1. Under these conditions, the pectin yield was
      predicted to be 2.71%. At a liquid-solid ratio less than 2.5% w/w in aqueous
      solution, the pectin extracted from okra presented non-Newtonian shear-thinning
      behavior and could be well described by the Cross model. The okra pectin showed
      predominantly viscous responses (G'<G") over a wide range of frequencies (10(-1)
      10 Hz) at 20% strain.

PMID- 25058754
TI  - Comparison of the serological tests ICT and ELISA for the diagnosis of alveolar
      echinococcosis in France.
AB  - Serological diagnosis of alveolar echinococcosis (AE) is a key element for
      efficient patient treatment management. A rapid immunochromatography test kit
      (ICT) using the recombinant Em18 antigen (rEm18) was recently developed. The aim
      of our study was to assess this test on a panel of sera from French patients with
      alveolar echinococcosis and control patients. In a blind test, a total of 112
      serum samples were tested including samples of AE (n = 30), cystic echinococcosis
      [CE] (n = 15), and polycystic echinococcosis [PE] (n = 1). For the comparison, 66
      sera from patients with hepatocarcinoma, fascioliasis, toxocariasis, Caroli's
      disease, or autoimmune chronic active hepatitis were used. The diagnostic test
      sets we used were the rEm18-ICT and two validated ELISAs with rEm18 and Em2-Em18
      antigens, respectively. For the ICT, 27/30 sera from AE patients, 4/15 sera from
      CE patients and the PE patient serum were positive. One serum from the control
      panel (toxocariasis) was positive for the ICT. The rEm18-ICT sensitivity (90.0%)
      and specificity (92.7%) for detection of Em18-specific antibodies confirmed it as
      a relevant tool for AE diagnosis. The rEm18-ELISA had a sensitivity of 86.7% and
      specificity of 91.5%, and the Em2-Em18-ELISA had a sensitivity of 96.7% and
      specificity of 87.8%. However, when AE patient sera are recorded as weak in
      intensity with the ICT, we recommend a double reading and use of a reference
      sample if the ICT is used for patient follow-up. 

PMID- 25058755
TI  - Professor Earl R. Owen--in memoriam.

PMID- 25058756
TI  - Effects of breast reduction on pulmonary function.
AB  - Macromastia causes several health problems, and reduction surgery alleviates them
      successfully. The purpose of this study was to investigate whether reduction
      mammaplasty improves possible impairments on pulmonary functions related to
      macromastia. Thirty-one patients participated in the study. Pulmonary function
      tests were performed before and 3 months after surgery with a spirometry.
      Preoperative and postoperative pulmonary function values were compared using a
      paired t test. Two patients were found to have mild restriction in preoperative
      spirometric analysis, and they went to normal range in postoperative analysis.
      All other patients were assessed as having normal values in both preoperative and
      postoperative analyses. Preoperative and postoperative forced vital capacity
      values were 2.72+/-0.06 and 2.79+/-0.05 L, respectively. The difference was
      statistically significant (paired t test, P=0.014). The other parameter in which
      breast reduction had statistically significant improvement was forced vital
      capacity performed/predicted ratio (paired t test, P=0.041). Additionally, the
      weight of resected breast tissue correlated significantly with the change of
      forced vital capacity (Pearson correlation coefficient=0.379, P=0.036). Breast
      reduction surgery improves the pulmonary function parameters that are mainly
      influenced by restrictive states. This result led us to consider that macromastia
      causes a relative restriction in chest wall compliance, and reduction of breast
      weight may enhance chest wall compliance and improve pulmonary function.

PMID- 25058757
TI  - Extracapsular invasion of sentinel lymph nodes is not associated with disease
      recurrence in breast cancer.
AB  - The purpose of this study was to evaluate the presence of extracapsular invasion
      (ECI) in positive sentinel lymph nodes (SLNs) as a predictor of disease
      recurrence in breast cancer. SLN biopsy was performed on 318 breasts of 316
      breast cancer patients, of which 50 (15.7%) had positive SLNs. Six (12.0%) of
      these 50 cases had disease recurrence. The clinicopathologic features of these
      cases were reviewed. The ECI at SLNs was not significantly associated with
      disease recurrence. The recurrence-free interval by Kaplan-Meier curves did not
      differ significantly among patients with and without ECI at SLNs. On the other
      hand, metastasis at non-SLNs was observed in 12 cases (24.0%) among the 50 cases
      with positive SLNs, and in the non-SLN metastasis group there were 7 patients
      with ECI at non-SLNs. Three of 7 cases with ECI at non-SLNs had disease
      recurrence and none of those 5 without ECI at non-SLNs had disease recurrence.
      Our current study suggests that the presence of ECI at metastatic SLNs is not
      associated with recurrent disease in breast cancer. Our results also imply that
      patients with ECI at positive non-SLNs have a high risk of disease recurrence.

PMID- 25058758
TI  - Utility of FDG-PET/CT in the evaluation of the response of locally advanced
      breast cancer to neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy (NAC) is effective in down-staging a primary tumor
      before surgery, and quick differentiation between responders to NAC and
      nonresponders is needed. We investigated the utility of [18F]fluorodeoxyglucose
      positron emission tomography (FDG-PET) and computed tomography (CT) in evaluating
      the therapeutic effectiveness of NAC. We investigated 25 patients who underwent
      NAC for stage II and III noninflammatory breast cancer. FDG-PET/CT was undertaken
      before and after NAC to determine the maximum standardized uptake value (SUVmax)
      reduction rate. Findings were compared with postoperative histopathologic
      evaluation of therapeutic response. It was not possible to accurately assess
      tumor response to NAC using CT. However, using the SUVmax reduction rate, we
      noted a significant difference (P=0.0420) between patients who were responsive
      and nonresponsive to NAC. The sensitivity and specificity were as high as 83.3%
      and 78.9%, respectively. This study demonstrated that FDG-PET/CT can
      differentiate responders from nonresponders. This improves patient management by
      avoiding unnecessary chemotherapy.

PMID- 25058759
TI  - Lobar lung resection in elderly patients with non-small cell lung carcinoma:
      impact of chronic obstructive pulmonary disease on surgical outcome.
AB  - The aim of this study was to evaluate the impact of chronic obstructive pulmonary
      disease (COPD) on the perioperative morbidity and mortality after lobar lung
      resection for non-small cell lung cancer (NSCLC) in patients aged 70 years and
      older. The medical records of 73 patients>=70 years who underwent lobar lung
      resection for NSCLC from 2003 to 2013 at our department were reviewed
      retrospectively. There were 27 patients with a mean age of 73.6 years and mean
      predicted forced expiratory volume in 1 s (FEV1) of 69.7% in the COPD group
      whereas remaining 46 patients (mean age=75.6 years) in the non-COPD group had a
      mean predicted FEV1 of 79.1%. There were no significant differences in
      perioperative morbidity (4.8% in the COPD group versus 17.4% in the non-COPD
      group) between both groups. We had no perioperative mortality in both groups.
      Lobar lung resection for NSCLC seems to be a safe therapy option for elderly
      patients with COPD who are fulfilling the common functional criteria of
      operability so that radical surgery should remain the mainstay of treatment for
      early-stage NSCLC in this increasing subpopulation.

PMID- 25058760
TI  - Scalp metastasis as the first sign of small-cell lung cancer: management and
      literature review.
AB  - Cutaneous metastasis from primary visceral malignancy is a relatively uncommon
      clinical entity, with a reported incidence ranging from 0.22% to 10% among
      various series. However, the presence of cutaneous metastasis as the first sign
      of a clinically silent visceral cancer is exceedingly rare. We describe here a
      case of an asymptomatic male patient who presented with a solitary scalp
      metastasis as the initial manifestation of an underlying small-cell lung cancer.
      Diagnostic evaluation revealed advanced disease. We conclude that the possibility
      of metastatic skin disease should always be considered in the differential
      diagnosis in patients with a history of smoking or lung cancer presenting with
      cutaneous nodules. Physicians should be aware of this rare clinical entity, and
      appropriate investigation should be arranged for early diagnosis and initiation
      of the appropriate treatment. The prognosis for most patients remains poor.

PMID- 25058761
TI  - Risk factors associated with sphincter-preserving resection in patients with low
      rectal cancer.
AB  - Abdominoperineal resection (APR) and sphincter-preserving resection (SPR) are the
      two primary surgical options for rectal cancer. Retrospectively we collected
      rectal cancer patients for SPR and APR observation between 2005 and 2007. The
      patient-related, tumor-related, and surgery-related variables of the SPR and APR
      groups were analyzed by using logistic regression techniques. The mean distance
      from the anal verge (DAV) of cancer is significantly higher in SPR than that in
      APR (P<0.001). In cancers with DAV<40 mm (SPR, 40 versus APR, 110), multivariate
      analysis shows that surgeon procedure volume (odds ratio [OR]=0.244; 95%
      confidence interval [CI]: 0.077-0.772; P=0.016) and neoadjuvant radiotherapy
      (OR=0.031; 95% CI: 0.002-0.396; P=0.008) are factors influencing SPR. In cancers
      with DAV ranging from 40 mm to 59 mm (SPR 190 versus APR 50), analysis shows that
      patient age (OR=2.139; 95% CI: 1.124-4.069; P=0.021), diabetes (OR=2.657; 95% CI:
      0.872-8.095; P=0.086), and colorectal surgeon (OR=0.122, 95% CI: 0.020-0.758;
      P=0.024), are influencing factors for SPR. The local recurrence and disease-free
      survival reveal no significant difference. A significant difference exists in
      DAV, surgeon specialization, procedure volume, age, diabetes, and neoadjuvant
      radiotherapy between SPR and APR.

PMID- 25058762
TI  - Short-term outcomes of simultaneous laparoscopic colectomy and hepatectomy for
      primary colorectal cancer with synchronous liver metastases.
AB  - Although simultaneous resection of primary colorectal cancer and synchronous
      liver metastases is reported to be safe and effective, the feasibility of a
      laparoscopic approach remains controversial. This study evaluated the safety,
      feasibility, and short-term outcomes of simultaneous laparoscopic surgery for
      primary colorectal cancer with synchronous liver metastases. From September 2008
      to December 2013, 10 patients underwent simultaneous laparoscopic resection of
      primary colorectal cancer and synchronous liver metastases with curative intent
      at our institute. The median operative time was 452 minutes, and the median
      estimated blood loss was 245 mL. Median times to discharge from the hospital and
      adjuvant chemotherapy were 13.5 and 44 postoperative days, respectively. Negative
      resection margins were achieved in all cases, with no postoperative mortality or
      major morbidity. Simultaneous laparoscopic colectomy and hepatectomy for primary
      colorectal cancer with synchronous liver metastases appears feasible with low
      morbidity and favorable outcomes.

PMID- 25058763
TI  - A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a
      French regional study.
AB  - Lymph node ratio (LNR) (positive lymph nodes/sampled lymph nodes) is predictive
      of survival in colon cancer. The aim of the present study was to validate the LNR
      as a prognostic factor and to determine the optimum LNR cutoff for distinguishing
      between "good prognosis" and "poor prognosis" colon cancer patients. From January
      2003 to December 2007, patients with TNM stage III colon cancer operated on with
      at least of 3 years of follow-up and not lost to follow-up were included in this
      retrospective study. The two primary endpoints were 3-year overall survival (OS)
      and disease-free survival (DFS) as a function of the LNR groups and the cutoff.
      One hundred seventy-eight patients were included. There was no correlation
      between the LNR group and 3-year OS (P=0.06) and a significant correlation
      between the LNR group and 3-year DFS (P=0.03). The optimal LNR cutoff of 10% was
      significantly correlated with 3-year OS (P=0.02) and DFS (P=0.02). The LNR was
      not an accurate prognostic factor when fewer than 12 lymph nodes were sampled.
      Clarification and simplification of the LNR classification are prerequisites for
      use of this system in randomized control trials. An LNR of 10% appears to be the
      optimal cutoff.

PMID- 25058764
TI  - Right colon carcinoma infiltrating the alimentary limb in a patient with
      biliopancreatic diversion.
AB  - Biliopancreatic diversion (BPD) has excellent results, with the average patient
      losing 60% to 80% of the excess weight in the first 2 years. However, the BPD
      works by malabsorption and malabsorptive problems may be experienced with the
      operation. Therefore, monitoring is necessary for life. In the recent literature
      there is some debate over the possibility that this technique can increase the
      risk of colon cancer secondary to the action of the unabsorbed food and bile acid
      on colonic mucosa. We report the case of a 42-year-old patient with a previous
      bariatric surgery (BPD with 50 cm common channel; 300 cm alimentary limb) who
      developed a very aggressive right colon cancer 6 years after the operation. We
      also review our series of 330 patients operated on during a 14-year period to try
      to answer if there is any relationship between BPD and colon cancer.

PMID- 25058765
TI  - Decreased leakage rate of colonic anastomoses by tachosil coating: an
      experimental study.
AB  - Colorectal anastomotic coating has been proposed as a means to lower the leakage
      rate. Prior to clinical testing, coating materials need thorough experimental
      evaluation to ensure safety and efficacy. The aim of this study was to evaluate
      Tachosil as an anastomotic coating agent. Technically insufficient colon
      anastomoses were created in 80 C57BL/6 mice, and in half of the animals the
      anastomoses were covered with Tachosil. The animals were examined for clinical
      signs of anastomotic leakage, and the breaking strength of the anastomoses was
      evaluated. The number of leakages was reduced by Tachosil coating (10/40 versus
      20/40 in controls; P=0.037). However, more cases of large bowel obstruction were
      found in the Tachosil group (12/40 versus 0/40 in controls; P<0.0005). Breaking
      strength was comparable between the Tachosil and control groups (0.49 N versus
      0.52 N, respectively; P=0.423). Clinical studies are needed to clarify the
      efficacy of Tachosil anastomotic coating.

PMID- 25058766
TI  - Surgery for diverticulitis: a re-evaluation of the changing trends.
AB  - The surgical management of diverticulitis continues to evolve but recent
      literature has not qualified just how different current practice is compared with
      the previous era. This study aims to update the seminal paper by Rodkey and Welch
      regarding indications and operation types performed for diverticulitis by
      comparing their findings with present practice at a community based institution.
      The charts of 407 patients admitted with "diverticular disease" between 2005 and
      2010 were identified. For each admission, patients' demographics, presentations
      and management were recorded. Direct comparisons were made with results from the
      study by Rodkey and Welch. Of the 407 admissions studied, the distribution was
      335 emergency and 72 elective. Medical management alone treated 90% of emergency
      admissions, while 4% required additional radiologic intervention. Emergency
      surgery was necessary in only 6% of cases with Hartmann's procedure being the
      most common procedure. Recurrent diverticulitis was a prime indication for
      elective surgery with 96% of cases undergoing a 1-staged procedure. Compared with
      the previous era, the nonoperative approach to managing acute diverticulitis is
      now applied for the vast majority of admissions. Improved success in medically
      temporizing patients in the present era has allowed for a higher percentage of
      successful single-staged elective surgeries.

PMID- 25058767
TI  - Carcinoma cecum presenting as right gluteal abscess through inferior lumbar
      triangle pathway--report of a rare case.
AB  - Gluteal abscess commonly follows intramuscular injections with contaminated
      needles. Carcinoma cecum is known to present with pericolic abscess due to
      microperforations and may rupture intraperitoneally. Gluteal abscess secondary to
      perforated carcinoma cecum with pericolic abscess is extremely uncommon. A 50
      year-old woman who was receiving intramuscular iron injections for anemia
      presented with a 10*10-cm abscess in the right gluteal region and a vague mass in
      the right iliac fossa. After investigations, a diagnosis of perforated carcinoma
      cecum with pericolic abscess tracking into the right gluteal region was made, and
      incision and drainage were done. Fine-needle aspiration cytology from the cecal
      growth revealed adenocarcinoma. Unfortunately, the patient was not willing to
      undergo definitive treatment. This case is being reported for its rarity and as
      an uncommon etiology for a common condition.

PMID- 25058768
TI  - The effectiveness of a rapid-access flexible sigmoidoscopy clinic in a district
      hospital.
AB  - Historically rapid-access colorectal clinics have had high proportions of
      nonconforming referrals from primary care physicians, which calls into question
      the clinics' efficacy. We aim to determine the effectiveness of our rapid-access
      flexible sigmoidoscopy clinic, and the adherence to the referral guidelines for
      suspected bowel cancer by general practitioners. We performed a 3-month
      retrospective audit to evaluate (1) the proportion of patients seen within 2
      weeks, (2) the appropriateness of referrals, (3) the proportion of patients with
      findings, and (4) the proportion of patients who had further tests. A total of 59
      patients (19 male, 40 female; age 35-86 years) were included in the study. All
      were offered an appointment within 2 weeks. Forty-one cases (82%) were
      appropriate referrals. Twenty-eight patients (47%) had pathology at
      sigmoidoscopy. Cancer pick-up rate was 6%. Thirty-seven patients (74%) had
      further investigations. We determined that our rapid-access clinic for
      symptomatic patients has high diagnostic accuracy and that access to early
      investigation is being used appropriately by general practitioners. In the
      current climate of spending cuts and streamlining services, our study confirms we
      are meeting targets for delivery of our colorectal service. The majority of
      referrals under the 2-week rule are appropriate. Rapid access to early
      investigation is being used appropriately by general practitioners contrasting
      previous studies with high proportions of nonconforming referrals.

PMID- 25058769
TI  - Drainage of periappendiceal abscess and removal of free fecalith--extraperitoneal
      approach.
AB  - Treatment of complicated acute appendicitis is controversial. The dilemma is
      further complicated by presence of free fecalith in a well-circumscribed abscess,
      which has been repeatedly demonstrated to be a major predicting factor of
      treatment failure of nonoperative treatment of acute appendicitis complicated
      with appendiceal abscess. If left behind after drainage of the abscess, further
      operations for removal of retained fecalith or recurrence of abscess might be
      required. However, little had been stressed over the significance of removal of
      the free fecalith when it was first encountered. We report our experience of
      drainage of appendiceal abscess and removal of free fecalith by taking an
      extraperitoneal approach. Both of our cases made a smooth recovery without any
      complication or recurrence after a 2-year follow-up. Treatment with this approach
      avoids many of the complications associated with formal laparotomy. Unlike image
      guided drainage or laparoscopic drainage, this procedure is relatively simple and
      straightforward and can be performed in any level of hospital, including private
      practitioners and in less well-developed areas and countries. With proper case
      selection, we recommend this approach as one of the alternatives in the treatment
      of late-presenting appendiceal abscess with free fecalith.

PMID- 25058770
TI  - Laparoscopic repair of a diaphragmatic hernia associated with radiofrequency
      ablation for hepatocellular carcinoma: lessons from a case and the review of the
      literature.
AB  - We describe the case of a patient with a diaphragmatic hernia associated with
      radiofrequency ablation for hepatocellular carcinoma who was successfully treated
      by laparoscopic surgery. A 62-year-old man with a long history of hepatitis C
      induced liver cirrhosis was admitted to our institution because of recurrent
      postprandial periumbilical pain. Eight years earlier, he had undergone
      radiofrequency ablation for hepatocellular carcinoma at hepatic segment VIII.
      Computed tomography, gastrografin enema examination revealed transverse colon
      obstruction because of a diaphragmatic hernia. We diagnosed diaphragmatic hernia
      associated with the prior radiofrequency ablation treatment. The patient
      underwent laparoscopic repair of the diaphragmatic hernia. Though the patient
      experienced the recurrence once, relaparoscopic treatment has improved the
      patient's conditions. Thus, diaphragmatic hernia can develop as a complication of
      radiofrequency ablation treatment. A laparoscopic approach is safe, feasible, and
      minimally invasive, even in patients with cirrhosis who develop iatrogenic
      diaphragmatic hernia as a complication of radiofrequency ablation treatment.

PMID- 25058771
TI  - ULTRAPRO Hernia System versus lichtenstein repair in treatment of primary
      inguinal hernias: a prospective randomized controlled study.
AB  - The Lichtenstein repair has been recommended as the gold standard for inguinal
      hernia repair. However, postoperative discomfort still constitutes a concern and
      an area for improvement. New mesh materials have been continuously introduced to
      achieve this goal. The goal of the present study was to investigate the outcomes
      of ULTRAPRO Hernia System (UHS) compared with Lichtenstein mesh repair. A total
      of 99 male patients with primary unilateral inguinal hernia were included in the
      study during the period of September 2010-January 2012. Patients with body mass
      index>30, comorbid diseases, and anesthetic risk of ASA-III and ASA-IV were
      excluded. The patients were randomly allocated to operation with the Lichtenstein
      technique (group L) or UHS. Demographics, operative and postoperative/recovery
      data, and short- and medium-term outcomes of the patients were recorded. A total
      of 50 patients in group L and 49 patients in group UHS were analyzed. The median
      follow-up time for the study was 33 months. There were no significant differences
      regarding demographics, complications, and rehabilitation between the groups.
      Overall, there was a prolonged operation time in the UHS group compared with the
      L group (UHS: 53.7+/-5.7 minutes; L: 44.5+/-5.5 minutes; P<0.001). UHS may
      provide results similar to those for the Lichtenstein technique in open repair of
      inguinal hernias regarding perioperative course, complications, recovery, and
      recurrence rates. However, because of reduced costs and the lack of need for the
      exploration of the preperitoneal space, we conclude that the Lichtenstein
      technique should be recommended as the first choice.

PMID- 25058772
TI  - Microsurgical intermediate subinguinal varicocelectomy.
AB  - This study was conducted to introduce a simple modification that can facilitate
      microsurgical subinguinal varicocelectomy (MSV) especially for surgeons
      inexperienced in microsurgical technique. A single surgeon performed
      microsurgical intermediate subinguinal varicocelectomy (MISV) on 52 patients with
      61 cases between September 2010 and August 2012. Patient age, varicocele grade,
      operation time, intraoperative findings, postoperative complications, and 3-month
      follow-up results were analyzed. Patient mean age was 28 years (range, 15-69
      years), and there were 9 bilateral cases. The mean operative time was 51 minutes
      (range, 34-109 minutes). We compared the first 31 cases to the second 30 cases,
      to assess investigator experience on operating times. The mean number of ligated
      veins was 5 (range, 3-10) in internal spermatic vein, 1 (range, 0-4) in external
      spermatic vein, and 1 (range, 0-3) in gubernacular vein. In 28 patients, the
      average postoperative sperm concentration at the 3-month follow-up was
      significantly higher than the preoperative sperm concentration (28.5+/
      18.2*10(6)/mL versus 10.5+/-23.0*10(6)/mL; P=0.003). Mean motility improved after
      MSIV (65.7%+/-18.2% versus 47.2%+/-21.7%; P=0.004). In conclusion, MISV appears
      comparable with MSV in terms of the high success rate, low complication rate, and
      low postoperative pain; and it can be easily accomplished by inexperienced
      surgeons.

PMID- 25058774
TI  - Giant spermatic cord liposarcoma.
AB  - We report a case of giant spermatic cord liposarcoma (SCL) in an 81-year-old
      patient, presenting with a huge scrotal mass that reached up to the knee joint.
      SCL is a rare tumor, and about 200 cases have been reported in the literature so
      far. Although 20% of liposarcomas arise in the retroperitoneum, only 0.1% present
      as incidental inguinal hernias. The occasional presence of myxoid stroma in well
      differentiated liposarcomas can lead to confusion with myxoid sarcoma subtypes.
      Correct diagnosis is critical and reflects remarkable differences in behavior and
      therapeutic choices.

PMID- 25058773
TI  - Parastomal hernia containing stomach.
AB  - Parastomal hernia is the most common late stomal complication. Its appearance is
      usually asymptomatic. We report a parastomal hernia containing stomach. A 69-year
      old patient with end colostomy arrived at the emergency room presenting with
      abdominal pain associated with vomiting and functioning stoma. She had a
      distended and painful abdomen without signs of peritoneal irritation and
      pericolostomic eventration in the left iliac fossa. X-ray visualized gastric
      fornix dilatation without dilated intestine bowels, and computed tomography
      showed parastomal incarcerated gastric herniation. Gastrografin (Bayer Australia
      Limited, New South Wales, Australia) was administered, showing no passage to
      duodenum. She underwent surgery, with stomal transposition and placement of onlay
      polypropylene mesh around the new stoma. Parastomal hernias are a frequent late
      complication of colostomy. Only four gastric parastomal hernia cases are reported
      in the literature. Three of these four cases required surgery. The placement of
      prosthetic mesh in the moment of stoma elaboration should be considered as a
      potential preventive measure.

PMID- 25058775
TI  - Mesh migration into urinary bladder after open ventral herniorrhaphy with mesh: a
      case report.
AB  - Ventral hernia repair with mesh products is of increasing popularity. The long
      term results of mesh repair of ventral hernia are superior to primary suture
      repair. However, occasional complications may still present. We report on a 77
      year-old man who underwent ventral hernia repair with a mesh 5 years ago with
      complication of mesh migration into the urinary bladder and enterovesical
      fistula. The patient presented with lower urinary tract symptoms initially. By
      urinalysis, persistent hematuria and pyuria were found after antibiotic
      treatment. For further investigation of hematuria, intravenous urography was
      performed, which revealed a faint radio-opaque patch at the right pelvis. To
      obtain a more precise relationship between the lesion and the adjacent organs,
      computed tomography and cystoscopy were arranged. They confirmed a mesh with
      stone formation in the urinary bladder. To remove the mesh, segmental resection
      of the ileum and cystorrhaphy were performed.

PMID- 25058776
TI  - A large retroperitoneal malignant solitary fibrous tumor.
AB  - We report on a large, retroperitoneal, malignant, solitary fibrous tumor (SFT)
      with high proliferation activity. A 43-year-old man was admitted to our
      department complaining of a palpable mass. Computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed a large retroperitoneal tumor occupying the
      entire abdominal cavity. A laparotomy was performed for diagnosis and treatment,
      which revealed a tumor in the retroperitoneum but with no invasion to the
      surrounding organs, thereby allowing safe macroscopic excision. Histologically,
      the tumor was composed of spindle-shaped cells with patternless pattern and a
      hemangiopericytomatous appearance. Moreover, immunohistochemical staining was
      positive for CD34, vimentin, Bcl-2, and CD99 and negative for desmin, S-100p, and
      smooth muscle actin (AMA). The tumor exhibited high cellularity, moderate mitotic
      activity, pleomorphism, necrosis, and hemorrhagic changes. In addition, the Ki-67
      labeling index was 37%. These findings confirmed the diagnosis of malignant SFT
      with high proliferation activity. Subsequently, adjuvant doxorubicin plus
      ifosfamide chemotherapy was performed. No signs of recurrence were observed 12
      months after the surgery.

PMID- 25058777
TI  - Substernal goiter: when is a sternotomy required?
AB  - The presence of substernal goiter is, per se, an indication for surgical
      management. Surgical approach of substernal goiter can most commonly be performed
      using the cervical access, but at times, a sternotomy or thoracotomy is
      necessary. The aim of this study was to identify the preoperative predictors of a
      sternotomy in the management of substernal goiter in order to provide better
      preoperative planning and patient consent. Between 2005 and 2012, 665 patients
      were referred to our clinic for thyroidectomy, 42 patients (6.3%) had substernal
      goiter and were included in this study. All substernal goiters were treated
      surgically, 38 (90.5%) by a cervical approach and 4 (9.5%) by full median
      sternotomy. All surgeries were successful, with no major postoperative
      complications. Minor postoperative complications of transient hypocalcemia and
      transient paralysis of the recurrent laryngeal nerve occurred in 5 (11.9%) and 2
      (4.7%) cases, respectively. Indication of median sternotomy was as follows:
      extension of goiter below the aortic arch, large thyroid tissue extending towards
      tracheal bifurcation, and ectopic thyroid tissue in the mediastinum. Substernal
      goiter can be removed through a cervical incision, but on rare occasions, a
      median sternotomy may be required.

PMID- 25058778
TI  - Recurrent cholangitis by biliary stasis due to non-obstructive afferent loop
      syndrome after pylorus-preserving pancreatoduodenectomy: report of a case.
AB  - We report a 71-year-old man who had undergone pylorus-preserving
      pancreatoduodenectomy (PPPD) using PPPD-IV reconstruction for cholangiocarcinoma.
      For 6 years thereafter, he had suffered recurrent cholangitis, and also a right
      liver abscess (S5/8), which required percutaneous drainage at 9 years after PPPD.
      At 16 years after PPPD, he had been admitted to the other hospital because of
      acute purulent cholangitis. Although medical treatment resolved the cholangitis,
      the patient was referred to our hospital because of dilatation of the
      intrahepatic biliary duct (B2). Peroral double-balloon enteroscopy revealed that
      the diameter of the hepaticojejunostomy anastomosis was 12 mm, and
      cholangiography detected intrahepatic stones. Lithotripsy was performed using a
      basket catheter. At 1 year after lithotripsy procedure, the patient is doing
      well. Hepatobiliary scintigraphy at 60 minutes after intravenous injection
      demonstrated that deposit of the tracer still remained in the upper afferent loop
      jejunum. Therefore, we considered that the recurrent cholangitis, liver abscess,
      and intrahepatic lithiasis have been caused by biliary stasis due to
      nonobstructive afferent loop syndrome. Biliary retention due to nonobstructive
      afferent loop syndrome may cause recurrent cholangitis or liver abscess after
      hepaticojejunostomy, and double-balloon enteroscopy and hepatobiliary
      scintigraphy are useful for the diagnosis of nonobstructive afferent loop
      syndrome.

PMID- 25058779
TI  - Delayed arterial hemorrhage after pancreaticoduodenectomy.
AB  - Delayed arterial hemorrhage is a rare complication of pancreaticoduodenectomy
      that is associated with a high mortality and has no standard management. Between
      2000 and 2011, 204 pancreaticoduodenectomies were performed, and there were 3
      cases of delayed arterial hemorrhage. We reviewed the role of endoscopy,
      laparotomy, and interventional radiology the management of delayed hemorrhage.
      One patient presented with intraluminal bleeding and upper gastrointestinal
      endoscopy failed to identify the bleeding site. Two patients presented with
      bleeding from the drain tube. Laparotomy was performed in the patient with
      intraluminal bleeding and interventional radiology was employed for the other 2
      patients. There was no hemorrhage-related mortality or rebleeding, but the
      patient who underwent laparotomy developed sepsis. Endoscopy may have no role in
      the initial management of delayed arterial hemorrhage after
      pancreaticoduodenectomy. Interventional radiology is less invasive compared with
      laparotomy, and may be considered as the first-line treatment for delayed
      arterial hemorrhage in pancreaticoduodenectomy patients.

PMID- 25058780
TI  - Bilorrhea secondary to bronchobiliary fistula.
AB  - Bronchobiliary fistula (BBF) is a rare condition which occurs most commonly as a
      complication of hydatid cyst liver disease. The following report describes a
      patient who presented with biliptysis 6 months following decortication of an
      empyema that had occurred following partial hepatectomy of a colon cancer
      metastasis. This is the only case to our knowledge that describes the
      presentation of a BBF in this context. The patient was diagnosed with BBF and
      successfully underwent open thoracotomy for fistulectomy and repair.

PMID- 25058781
TI  - An extraordinary case of axillary contracture: trapped healthy skin and its
      adnexes under contracted scar.
AB  - Although striking improvements have been achieved in overall management of burn
      injury, postburn contractures are still an ongoing challenge to burn surgeons.
      Axillary adduction contracture is one of the most common types of these disabling
      postburn complications that usually result from suboptimal treatment after acute
      burns. An unusual and complicated case of axillary contracture in which the
      unburned, healthy axillary dome skin was trapped as a cystic mass under the
      scarred area was reconstructed by transfer of a big (17*13-cm) thoracodorsal
      artery perforator flap after contracture release. The result was satisfactory in
      terms of function and acceptable cosmetically. The underlying reasons for the
      inadequate treatment the patient received after surviving a severe electrical
      injury were discussed.

PMID- 25058782
TI  - Application of split gluteus maximus muscle--adipofascial turnover flap and
      subcutaneous tension-reducing suture technique in repair of decubitus ulcers.
AB  - The purpose of this study was to study the clinical effect of split gluteus
      maximus muscle-adipofascial turnover flap and tension-reducing suture in the
      treatment of decubitus ulcers. Thirty-one cases of sacrococcygeal decubitus
      ulcers were repaired by split gluteus maximus muscle-adipofascial turnover flap.
      The surface of flaps ranged from 5*6 cm to 7*8 cm. The skin was then closed,
      primarily using subcutaneous tension-reducing suture. Eighty-eight percent of the
      flaps (27 of 31) healed primarily. The split gluteus maximus muscle-adipofascial
      turnover flap and tension-reducing suture technique was found to be a highly
      efficient method of repairing decubitus ulcers with a relatively low ratio of
      recurrence.

PMID- 25058783
TI  - Salvage lymphadenectomy for recurrent esophageal cancer after chemoradiotherapy.
AB  - Although salvage esophagectomies are widely performed, reports on salvage
      lymphadenectomy (SL) are few. We review our SL cases to clarify the indications.
      Fifty-five patients with esophageal cancer underwent chemoradiotherapy or
      radiotherapy, including 3 patients with single lymph node (LN) recurrences and
      one with allochronic double cervical node recurrence. Our department removed 5
      recurrent LNs from these 4 patients. In Case 1, right supraclavicular LN was
      judged to be metastatic and R0 resection was carried out; he is alive without
      recurrence. In Case 2, we found, allochronically, metastases in his left cervical
      paraesophageal LN and left supraclavicular LN; residual tumors were R1 in both
      lesions. He is alive despite esophageal recurrence. In Case 3, a lymphadenectomy
      was performed on his thoracic para-aortic LN; however, tumor was removed
      incompletely, and he died 4 months after SL from disease progression. In Case 4,
      a subcarinal LN was thought to be metastatic, and was removed but no malignant
      tissues detected. He died 17 months after SL from pneumonia. Our experiences
      suggest that some patients survive relatively long with SL. Moreover, molecular
      examination of resected lesions could guide subsequent therapies. SL might be
      more widely used for these patients if not otherwise contraindicated.

PMID- 25058784
TI  - Mucosal esophageal squamous cell carcinoma with intramural gastric metastasis
      invading liver and pancreas: a case report.
AB  - A 59-year-old Japanese man was admitted to our hospital because of a 1-month
      history of dysphagia. Endoscopic examination revealed a superficial esophageal
      squamous cell carcinoma and a giant gastric tumor. Computed tomography showed
      that the gastric tumor was directly invading the liver and pancreas. Because of
      the risk of the gastric tumor causing obstruction and bleeding, we performed a
      subtotal esophagectomy, proximal gastrectomy, left lateral segmentectomy of
      liver, and pancreatosplenectomy with gastric tube reconstruction. Final
      pathological findings were superficial esophageal carcinoma penetrating the
      muscularis mucosae with an intramural gastric metastasis directly invading the
      liver and pancreas. The patient received postoperative adjuvant chemotherapy, yet
      died 8 months postoperatively of complications of local recurrence. Early-stage
      esophageal carcinoma with intramural gastric metastasis is very rare. To our
      knowledge, this is the first case of mucosal esophageal carcinoma with intramural
      gastric metastasis directly invading other organs.

PMID- 25058785
TI  - Single-incision laparoscopic surgery for a small-intestinal gastrointestinal
      stromal tumor: report of a case.
AB  - Our report concerns a 64-year-old man with a small-intestinal gastrointestinal
      stromal tumor (GIST), which was successfully treated with single-incision
      laparoscopic surgery (SILS). Small-bowel endoscopy detected a submucosal tumor
      located approximately 10 cm from the ligament of Treitz in the wall of the
      proximal jejunum. Contrast-enhanced computed tomography revealed a tumor
      (diameter, 4 cm) containing high- and low-density areas in the proximal jejunum.
      On 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET), the tumor
      demonstrated intense FDG uptake (maximum standard uptake value, 3.82), whereas it
      displayed high signal intensity on diffusion-weighted magnetic resonance images.
      No metastatic lesions were observed. The patient was diagnosed with a jejunal
      GIST. Wedge resection of the jejunum was performed using the SILS procedure. The
      tumor was histopathologically diagnosed as a low-grade malignant GIST. SILS is a
      useful resection technique for small-intestinal GIST.

PMID- 25058786
TI  - Surgical interventions for late complications of arteriovenous fistulas.
AB  - Our aim was to determine the most effective surgical treatment for arteriovenous
      fistula (AVF) complications after all other methods of salvage have failed. We
      evaluated 110 patients for 139 complications that occurred after the initial AVF
      placement and for whom surgical intervention was the last hope for retaining
      fistula access. Vascular steal syndrome and venous hypertension were the most
      common complications seen in our patients. The anastomoses of 17 of the vascular
      steal syndrome cases were narrowed either by stitches or by a
      polytetrafluoroethylene graft. The second most performed revision surgery was
      excision of the aneurysm and repair with primary suturing, followed by excision
      of the aneurysm and interposition grafting. Successful surgical outcomes were
      achieved in 111 of 139 procedures after revision surgery without constructing a
      new AVF. AVF salvage surgery is of paramount importance in order to increase the
      patency rate, which prolongs survival and increases the patient's quality of
      life.

PMID- 25058787
TI  - Ultrasound-guided vein puncture versus surgical cut-down technique in totally
      implantable venous access devices (TIVADS): a prospective comparative study on
      safety, efficacy andcomplications.

PMID- 25058789
TI  - Reducing radiation dose without compromising image quality in preoperative
      perforator flap imaging with CTA using ASIR technology.
AB  - Computed tomographic angiography (CTA) has become a mainstay in preoperative
      perforator flap planning in the modern era of reconstructive surgery. However,
      the increased use of CTA does raise the concern of radiation exposure to
      patients. Several techniques have been developed to decrease radiation dosage
      without compromising image quality, with varying results. The most recent advance
      is in the improvement of image reconstruction using an adaptive statistical
      iterative reconstruction (ASIR) algorithm. We sought to evaluate the image
      quality of ASIR in preoperative deep inferior epigastric perforator (DIEP) flap
      surgery, through a direct comparison with conventional filtered back projection
      (FBP) images. A prospective review of 60 consecutive ASIR and 60 consecutive FBP
      CTA images using similar protocol (except for radiation dosage) was undertaken,
      analyzed by 2 independent reviewers. In both groups, we were able to accurately
      identify axial arteries and their perforators. Subjective analysis of image
      quality demonstrated no statistically significant difference between techniques.
      ASIR can thus be used for preoperative imaging with similar image quality to FBP,
      but with a 60% reduction in radiation delivery to patients.

PMID- 25058788
TI  - Heterotopic mesenteric ossification after a ruptured abdominal aortic aneurism:
      case report with a review of literatures.
AB  - Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra
      abdominal ossification of unknown origin. An 88-year-old man developed an
      intestinal obstruction 2 weeks after undergoing an operation for a ruptured
      abdominal aortic aneurysm, resulting in intestinal obstructions those did not
      improved concervatively. During relaparotomy performed 30 days after the first
      operation, hard adhesions of the small intestine and mesentery were found; these
      adhesions were difficult to separate without damaging the serosa of the small
      intestine. We removed 240 cm of the small intestine and performed a jejuno-ileo
      anastomosis. Microscopically, trabecular bone tissue had increased irregularly in
      the fat tissue of the nodules with fibrosis, which were partially lined with
      osteoblasts. Accordingly, we histopathologically diagnosed the patient as having
      HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence
      of HMO. No signs of recurrence have occurred as of one year after the second
      operation.

PMID- 25058792
TI  - Locus of onset and subpopulation specificity of in vivo ethanol effect in the
      reciprocal ventral tegmental area-nucleus accumbens circuit.
AB  - Elevated levels of dopamine in the nucleus accumbens (nAc) as a consequence of
      increased activation of dopaminergic neurons in the VTA are associated with the
      reinforcing properties of ethanol consumption, but whether the initiation of drug
      response is connected to a direct activation of dopaminergic cell bodies in the
      VTA region or involves GABAergic neurons in VTA and/or the nAc is unclear. To
      this end, neuronal firing rate was recorded simultaneously in the VTA and nAc of
      awake and freely-moving C57BL6/J mice receiving an intraperitoneal (i.p.)
      injection of ethanol (0.75, 2.0, or 3.5g/kg) or saline. Recorded units were
      classified based on electrophysiological properties and the pharmacological
      response to the dopamine D2 receptor agonist quinpirole into putative
      dopaminergic (DA) neurons and fast-spiking or slow-spiking putative GABAergic
      neurons. Our data show that ethanol acutely decreases the firing frequency of
      GABAergic units in both the VTA and nAc in a dose-dependent manner, and enhances
      the firing rate of DA neurons. In order to define the onset of ethanol-induced
      rate changes normalized population vectors describing the collective firing rate
      of classes of neurons over time were generated and compared with saline
      treatment. Population vectors of DA neurons in the VTA and GABAergic units in the
      nAc showed a significant deviation from the saline condition within 40s following
      ethanol-administration (2.0g/kg), while inhibition of GABAergic units in the VTA
      had a slower onset. In conclusion, the data presented here suggests that EtOH
      exerts a direct effect on DA firing frequency, but that decreased firing
      frequency of inhibitory neurons in VTA and nAc contributes to the dopamine
      elevating properties of ethanol. 

PMID- 25058793
TI  - A quantum mechanical "jack in the box": rapid rearrangement of a tetrahedryl
      tetrahedrane via heavy atom tunneling.
AB  - A bridged tetrahedryl-tetrahedrane ("TT") was, theoretically, recognized as the
      holder of the chemical record for the shortest C-C single bond in a stable
      molecule. However, owing to its strained nature, this molecule is prone to
      rearrange to a carbene via ring contraction. Although TT was predicted to be
      stable to rearrangement at very low temperatures, our calculations find that, due
      to carbon quantum mechanical tunneling, even at 0 K it will immediately
      rearrange, with a half-life of only 4 ms. TT provides an excellent example of why
      tunneling effect should be considered in the stability analysis of a
      theoretically conceived molecule, even at cryogenic temperatures. 

PMID- 25058791
TI  - Histone deacetylase mediates the decrease in drebrin cluster density induced by
      amyloid beta oligomers.
AB  - Dendritic spine defects are found in a number of cognitive disorders, including
      Alzheimer's disease (AD). Amyloid beta (Abeta) toxicity is mediated not only by
      the fibrillar form of the protein, but also by the soluble oligomers (Abeta
      derived diffusible ligands, ADDLs). Drebrin is an actin-binding protein that is
      located at mature dendritic spines. Because drebrin expression is decreased in AD
      brains and in cultured neurons exposed to Abeta, it is thought that drebrin is
      closely associated with cognitive functions. Recent studies show that histone
      deacetylase (HDAC) activity is elevated in the AD mouse model, and that memory
      impairments in these animals can be ameliorated by HDAC inhibitors. In addition,
      spine loss and memory impairment in HDAC2 over-expressing mice are ameliorated by
      chronic HDAC inhibitor treatment. Therefore, we hypothesized that the regulation
      of histone acetylation/deacetylation is critical to synaptic functioning. In this
      study, we examined the relationship between HDAC activity and synaptic defects
      induced by ADDLs using an HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA).
      We show that ADDLs reduce the cluster density of drebrin along dendrites without
      reducing drebrin expression. SAHA markedly increased the acetylation of histone
      proteins, and it simultaneously attenuated the ADDL-induced decrease in drebrin
      cluster density. In comparison, SAHA treatment did not affect the density of
      drebrin clusters or dendritic protrusions in control neurons. Therefore, SAHA
      likely inhibits ADDL-induced drebrin loss from dendritic spines by stabilizing
      drebrin in these structures, rather than by increasing drebrin clusters or
      dendritic protrusions. Taken together, our findings suggest that HDAC is involved
      in ADDL-induced synaptic defects, and that the regulation of histone acetylation
      plays an important role in modulating actin cytoskeletal dynamics in dendritic
      spines under cellular stress conditions, such as ADDL exposure. 

PMID- 25058794
TI  - Executive function and attention in young adults with and without developmental
      coordination disorder--a comparative study.
AB  - The current research aimed at examining the executive function (EF) of young
      adults with Developmental Coordination Disorder (DCD) in comparison to young
      adults without DCD. The study used a randomized cohort (N=429) of young adults
      with DCD (n=135), borderline DCD (n=149) and control (n=145), from a previous
      study. This initial cohort was asked to participate in the current study three to
      four years later. Twenty-five individuals with DCD (mean age=24 years, 1 month
      [SD=0.88]; 18 males), 30 with borderline DCD (mean age=24 years, 2 month
      [SD=0.98]; 18 males) and 41 without DCD (mean age=25 years, 2 months [SD=1.91];
      20 males) participated in this study. Participants completed the BRIEF-A
      questionnaire, assessing EF abilities and the WURS questionnaire, assessing
      attention abilities. The DCD and borderline DCD groups had significantly lower EF
      profiles in comparison with the control group but no significant differences were
      found between the DCD and borderline DCD groups. While a high percentage of
      attention problems were found in both DCD groups, the executive functioning
      profiles remained consistent even when using the attention component as a
      covariate. The study results suggest that young adults with DCD have EF problems
      which remain consistent with or without attention difficulties. 

PMID- 25058795
TI  - Neuroprotective effects of dietary supplement Kang-fu-ling against high-power
      microwave through antioxidant action.
AB  - Kang-fu-ling (KFL) is a polybotanical dietary supplement with antioxidant
      properties. This study aimed to evaluate the potential protective effects of KFL
      on cognitive deficit induced by high-power microwave (HPM) and the underlying
      mechanism for this neuroprotection. The electron spin resonance technique was
      employed to evaluate the free radical scavenging activity of KFL in vitro and KFL
      exhibited scavenging hydroxyl radical activity. KFL at doses of 0.75, 1.5 and 3 g
      kg(-1) and vehicle were administered orally once daily for 14 days to male Wistar
      rats after being exposed to 30 mW cm(-2) HPM for 15 minutes. KFL reversed HPM
      induced memory loss and the histopathological changes in hippocampus of rats. In
      addition, KFL displayed a protective effect against HPM-induced oxidative stress
      and activated the nuclear factor-E2-related factor 2 (Nrf2) and its target genes
      in the hippocampus of rats. The Nrf2-antioxidant response element (ARE) signaling
      pathway may be involved in the neuroprotective effects of KFL against HPM-induced
      oxidative stress. In summary, the dietary supplement KFL is a promising natural
      complex, which ameliorates oxidative stress, with neuroprotective effects against
      HPM. 

PMID- 25058796
TI  - Influence of electrotaxis on cell behaviour.
AB  - Understanding the mechanism of cell migration and interaction with the
      microenvironment is not only of critical significance to the function and biology
      of cells, but also has extreme relevance and impact on physiological processes
      and diseases such as morphogenesis, wound healing, neuron guidance, and cancer
      metastasis. External guidance factors such as topography and physical cues of the
      microenvironment promote directional migration and can target specific changes in
      cell motility and signalling mechanisms. Recent studies have shown that cells can
      directionally respond to applied electric fields (EFs), in both in vitro and in
      vivo settings, a phenomenon called electrotaxis. However, the exact cellular
      mechanisms for sensing electrical signals are still not fully well understood,
      and it is thus far unknown how cells recognize and respond to electric fields,
      although some studies have suggested that electro-migration of some cell surface
      receptors and ion channels in cells could be involved. Applied electric fields
      may have a potential clinical role in guiding cell migration and present a more
      precise manageability to change the magnitude and direction of the electric field
      than most other guidance cues such as chemical cues. Here we present a review of
      recent studies used for studying electrotaxis to point out similarities, identify
      points of disagreement, and stimulate new directions for investigation. Insights
      into the mechanisms by which applied EFs direct cell migration, morphological
      change and development will enable current and future therapeutic applications to
      be optimized. 

PMID- 25058797
TI  - Self-aggregation and liquid crystalline behavior of new ester-functionalized
      quinuclidinolium surfactants.
AB  - A new type of ester-based cationic surfactant having a quinuclidinolium headgroup
      has been synthesized starting from linear fatty alcohols and has been
      characterized using spectroscopic techniques. The self-aggregation and
      thermodynamic properties of these surfactants have been investigated by pendant
      drop surface tensiometry and conductivity measurements. The liquid crystalline
      behaviors of these surfactants were investigated by small-angle X-ray scattering
      (SAXS) technique. The quinuclidinolium headgroup demonstrated a unique ability to
      interlock among themselves thus affecting the physicochemical properties of
      surfactants in aqueous solution. The current research finding supports the new
      concept of headgroup interlocking which is supported by 1D and 2D NMR studies. 

PMID- 25058799
TI  - Hydrogen sulfide as a potent cardiovascular protective agent.
AB  - Hydrogen sulfide (H2S) is a well-known toxic gas with the characteristic smell of
      rotten eggs. It is synthesized endogenously in mammals from the sulfur-containing
      amino acid l-cysteine by the action of several distinct enzymes: cystathionine
      gamma-lyase (CSE), cystathionine-beta-synthase (CBS), and 3-mercaptopyruvate
      sulfurtransferase (3-MST) along with cysteine aminotransferase (CAT). In
      particular, CSE is considered to be the major H2S-producing enzyme in the
      cardiovascular system. As the third gasotransmitter next to nitric oxide (NO) and
      carbon monoxide (CO), H2S plays an important role in the regulation of
      vasodilation, angiogenesis, inflammation, oxidative stress and apoptosis. Growing
      evidence has demonstrated that this gas exerts a significant protective effect
      against the progression of cardiovascular diseases by a number of mechanisms such
      as vasorelaxation, inhibition of cardiovascular remodeling and resistance to form
      foam cells. The aim of this review is to provide an overview of the physiological
      functions of H2S and its protection against several major cardiovascular
      diseases, and to explore its potential health and therapeutic benefits. A better
      understanding will help develop novel H2S-based therapeutic interventions for
      these diseases. 

PMID- 25058801
TI  - Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 15.
      Effects of the pyridyl substituents and fused exocyclic rings on the UV-visible
      spectroscopic properties of Mg(II)-porphyrazines: a combined experimental and
      DFT/TDDFT study.
AB  - Two new Mg(II) porphyrazine macrocycles, the octakis(2-pyridyl)porphyrazinato
      magnesium(II), [Py8PzMg(H2O)], and the tetrakis-[6,7-di(2
      pyridyl)quinoxalino]porphyrazinato-magnesium(II), [Py8QxPzMg(H2O)], were prepared
      by Mg-template macrocyclization processes, and their general physicochemical
      properties were examined. The previously reported porphyrazine analog, the
      tetrakis-2,3-[5,6-di(2-pyridyl)-pyrazino]porphyrazinato-magnesium(II),
      [Py8PyzPzMg(H2O)], has been also considered in the present work. The UV-visible
      solution spectra in nonaqueous solvents of this triad of externally
      octapyridinated Mg(II) complexes exhibit the usual profile observed for
      phthalocyanine and porphyrazine macrocycles, with intense absorptions in the
      Soret (300-450 nm) and Q band (600-800 nm) regions. It is observed that the Q
      band maximum sensibly shifts toward the red with peak values at 635 -> 658 -> 759
      nm along the series [Py8PzMg(H2O)], [Py8PyzPzMg(H2O)], and [Py8QxPzMg(H2O)], as
      the extension of the macrocycle pi-system increases. TDDFT calculations of the
      electronic absorption spectra were performed for the related water-free model
      compounds [Py8PzMg], [Py8PyzPzMg], and [Py8QxPzMg] to provide an interpretation
      of the UV-visible spectral changes occurring upon introduction of the pyrazine
      and quinoxaline rings at the periphery of the Pz macrocycle. To discriminate the
      electronic effects of the fused exocyclic rings from those of the appended 2
      pyridyl rings, the UV-visible spectra of [PzMg] and [PyzPzMg] were also
      theoretically investigated. The theoretical results prove to agree very well with
      the experimental data, providing an accurate description of the UV-visible
      spectra. The observed spectral changes are interpreted on the basis of the
      electronic structure changes occurring along the series. 

PMID- 25058800
TI  - Primaquine-induced severe methemoglobinemia developed during treatment of
      Plasmodium vivax malarial infection in an Indian family associated with a novel
      mutation (p.Agr57Trp) in the CYB5R3 gene.

PMID- 25058802
TI  - Study of factors governing oil-water separation process using TiO2 films prepared
      by spray deposition of nanoparticle dispersions.
AB  - Surfaces which possess extraordinary water attraction or repellency depend on
      surface energy, surface chemistry, and nano- and microscale surface roughness.
      Synergistic superhydrophilic-underwater superoleophobic surfaces were fabricated
      by spray deposition of nanostructured TiO2 on stainless steel mesh substrates.
      The coated meshes were then used to study gravity driven oil-water separation,
      where only the water from the oil-water mixture is allowed to permeate through
      the mesh. Oil-water separation efficiencies of up to 99% could be achieved
      through the coated mesh of pore sizes 50 and 100 MUm, compared to no separation
      at all, that was observed in the case of uncoated meshes of the same material and
      pore sizes. An adsorbed water on the TiO2 coated surface, formation of a water
      film between the wires that form the mesh and the underwater superoleophobicity
      of the structured surface are the key factors that contribute to the enhanced
      efficiency observed in oil-water separation. The nature of the oil-water
      separation process using this coated mesh (in which the mesh allows water to pass
      through the porous structure but resists wetting by the oil phase) minimizes the
      fouling of mesh so that the need for frequent replacement of the separating
      medium is reduced. The fabrication approach presented here can be applied for
      coating large surface areas and to develop a large-scale oil-water separation
      facility for oil-field applications and petroleum industries. 

PMID- 25058803
TI  - The effect of a preoperative single-dose methylprednisolone on postoperative pain
      after abdominal hysterectomy: a randomized controlled trial.
AB  - OBJECTIVE: Methylprednisolone has been shown to have analgesic effects after
      orthopedic surgery. The objective of this trial was to compare the effect of 125
      mg methylprednisolone with placebo on postoperative pain after abdominal
      hysterectomy. STUDY DESIGN: In this randomized double-blinded placebo-controlled
      trial women scheduled for elective abdominal hysterectomy (n=59) were randomized
      to preoperatively receive either 125 mg methylprednisolone or saline
      intravenously. Primary outcome was postoperative pain measured on a 0.0-10.0
      visual analog scale and assessed at rest and during mobilization repeatedly the
      first 24h and daily on the 2nd to 7th postoperative day. Secondary outcomes were
      postoperative use of opioids and antiemetics, vomiting, C-reactive protein
      levels, and time to mobilization and discharge. Repeated measures including the
      primary outcome were analyzed with linear mixed models. RESULTS: Forty-nine cases
      were analyzed (methylprednisolone n=25, placebo n=24). Pain scores were
      significantly higher in the methylprednisolone group compared to the placebo
      group during mobilization (0.79 [95% confidence intervals (CI) 0.07-1.50] P=0.03)
      but not at rest (0.55 [95% CI: -0.06 to 1.16] P=0.08). There was no difference
      between the methylprednisolone and placebo group regarding use of opioids
      (P=0.24) and antiemetics (P=0.14), number of vomits (P=0.26), and time to
      mobilization (P=0.24) and discharge (P=0.28). C-reactive protein levels were
      significantly higher in the placebo group (P=0.01). CONCLUSIONS: This trial
      showed no beneficial effect of methylprednisolone on postoperative pain after
      abdominal hysterectomy. Methylprednisolone significantly lowered postoperative
      CRP levels. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov:
      www.clinicaltrials.gov: NCT01106547.

PMID- 25058805
TI  - Ultrafast relaxation dynamics of phosphine-protected, rod-shaped Au20 clusters:
      interplay between solvation and surface trapping.
AB  - The exact interaction between Au cores and surface ligands remains largely
      unknown because of the complexity of the structure and chemistry of ligand/Au
      core interfaces in ligand-protected Au nanoclusters (AuNCs), which are commonly
      found in many organic-inorganic complexes. Here, femtosecond transient absorption
      measurement of the excited-state dynamics of a newly synthesized phosphine
      protected cluster [Au20(PPhpy2)10Cl4]Cl2 (1) is reported. Intramolecular charge
      transfer (ICT) from the Au core to the peripheral ligands was identified.
      Furthermore, we found that solvation strongly affected ICT at ligand/Au-core
      interfaces while by choosing several typical alcoholic solvents with different
      intrinsic solvation times, we successfully observed that excited-state relaxation
      dynamics together with displacive excited coherent oscillation of Au20 clusters
      were significantly modulated through the competition between solvation and
      surface trapping. The results provide a fundamental understanding of the
      structure-property relationships of the solvation-dependent core-shell
      interaction of AuNCs for the potential applications in catalysis, sensing and
      nanoelectronics.

PMID- 25058804
TI  - The effect of uterine straightening by bladder distention before outpatient
      hysteroscopy: a randomised clinical trial.
AB  - OBJECTIVE: To investigate the effect of bladder distention before outpatient
      hysteroscopy (OH). STUDY DESIGN: Initially, 120 eligible patients were
      approached, and a total of 102 patients were recruited into the randomised
      controlled trial. OH was completed successfully in 97 patients. Pain scoring
      (visual analogue scale) and the ease of cervical entry (Likert scale) were the
      primary outcome measures. The secondary outcome measures in this study were the
      duration of the procedure and patient acceptability (Likert scale). RESULT(S):
      Bladder distention before OH was related to easier cervical entry, a shorter
      procedural time and low pain scoring in patients who underwent the procedure with
      a full bladder. CONCLUSION(S): Bladder distention before OH significantly
      improved the pain score of patients and increases the feasibility of the
      hysteroscopy procedure.

PMID- 25058806
TI  - Predator-prey systems depend on a prey refuge.
AB  - Models of near-exclusive predator-prey systems such as that of the Canadian lynx
      and snowshoe hare have included factors such as a second prey species, a Holling
      Type II predator response and climatic or seasonal effects to reproduce sub-sets
      of six signature patterns in the empirical data. We present an agent-based model
      which does not require the factors or constraints of previous models to reproduce
      all six patterns in persistent populations. Our parsimonious model represents a
      generalised predator and prey species with a small prey refuge. The lack of the
      constraints of previous models, considered to be important for those models,
      casts doubt on the current hypothesised mechanisms of exclusive predator-prey
      systems. The implication for management of the lynx, a protected species, is that
      maintenance of an heterogeneous environment offering natural refuge areas for the
      hare is the most important factor for the conservation of this species. 

PMID- 25058807
TI  - Online quantitative proteomics p-value calculator for permutation-based
      statistical testing of peptide ratios.
AB  - The utility of high-throughput quantitative proteomics to identify differentially
      abundant proteins en-masse relies on suitable and accessible statistical
      methodology, which remains mostly an unmet need. We present a free web-based
      tool, called Quantitative Proteomics p-value Calculator (QPPC), designed for
      accessibility and usability by proteomics scientists and biologists. Being an
      online tool, there is no requirement for software installation. Furthermore, QPPC
      accepts generic peptide ratio data generated by any mass spectrometer and
      database search engine. Importantly, QPPC utilizes the permutation test that we
      recently found to be superior to other methods for analysis of peptide ratios
      because it does not assume normal distributions.1 QPPC assists the user in
      selecting significantly altered proteins based on numerical fold change, or
      standard deviation from the mean or median, together with the permutation p
      value. Output is in the form of comma separated values files, along with
      graphical visualization using volcano plots and histograms. We evaluate the
      optimal parameters for use of QPPC, including the permutation level and the
      effect of outlier and contaminant peptides on p-value variability. The optimal
      parameters defined are deployed as default for the web-tool at
      http://qppc.di.uq.edu.au/ . 

PMID- 25058808
TI  - On the hydrophilicity of polyzwitterion poly (N,N-dimethyl-N-(3
      (methacrylamido)propyl)ammoniopropane sulfonate) in water, deuterated water, and
      aqueous salt solutions.
AB  - A series of zwitterionic model polymers with defined molar masses up to 150,000
      Da and defined end groups are prepared from sulfobetaine monomer N,N-dimethyl-N
      (3-(methacrylamido)propyl)ammoniopropanesulfonate (SPP). Polymers are synthesized
      by reversible addition-fragmentation chain transfer polymerization (RAFT) using a
      functional chain transfer agent labeled with a fluorescent probe. Their upper
      critical solution temperature-type coil-to-globule phase transition in water,
      deuterated water, and various salt solutions is studied by turbidimetry. Cloud
      points increase with polyzwitterion concentration and molar mass, being
      considerably higher in D2O than in H2O. Moreover, cloud points are strongly
      affected by the amount and nature of added salts. Typically, they increase with
      increasing salt concentration up to a maximum value, whereas further addition of
      salt lowers the cloud points again, mostly down to below freezing point. The
      different salting-in and salting-out effects of the studied anions can be
      correlated with the Hofmeister series. In physiological sodium chloride solution
      and in phosphate buffered saline (PBS), the cloud point is suppressed even for
      high molar mass samples. Accordingly, SPP-polymers behave strongly hydrophilic
      under most conditions encountered in biomedical applications. However, the direct
      transfer of results from model studies in D2O, using, e.g. (1)H NMR or neutron
      scattering techniques, to 'normal' systems in H2O is not obvious. 

PMID- 25058809
TI  - Antiviral atropisomers: conformational energy surfaces by NMR for host-directed
      myxovirus blockers.
AB  - Biologically active organic molecules characterized by a high single bond
      torsional barrier generate isolable isomers (atropisomers) and offer a unique
      stereochemical component to the design of selective therapeutic agents. The
      present work presents a nanomolar active inhibitor of myxoviruses, which most
      likely acts by blocking one or more cellular host proteins but also,
      serendipitously, exhibits axial chirality with an energy barrier of DeltaG((++))
      >=30 kcal/mol. The latter has been probed by variable temperature NMR and
      microwave irradiation and by high level DFT transition state analysis and force
      field calculations. Full conformational profiles of the corresponding (aR,S) and
      (aS,S) atropisomers at ambient temperature were derived by conformer
      deconvolution with NAMFIS (NMR Analysis by Molecular Flexibility In Solution)
      methodology to generate seven and eight individual conformations, each assigned a
      % population. An accurate evaluation of a key torsion angle at the center of the
      molecules associated with a (3)JC-S-C-H coupling constant was obtained by mapping
      the S-C bond rotation with the MPW1PW91/6-31G-d,p DFT method followed by fitting
      the resulting dihedral angles and J-values to a Karplus expression. Accordingly,
      we have developed a complete conformational profile of diastereomeric
      atropisomers consistent with both high and low rotational barriers. We expect
      this assessment to assist the rationalization of the selectivity of the two
      (aR,S) and (aS,S) forms against host proteins, while offering insights into their
      divergent toxicity behavior.

PMID- 25058810
TI  - Non-Suicidal Self-Injury among Adolescents in Amman, Jordan.
AB  - While previous research has demonstrated cross-national differences in non
      suicidal self-injury (NSSI), most studies to date have taken place in North
      America. The present study investigated the prevalence and characteristics of
      NSSI in a sample of 952 Jordanian adolescents (49.8% female) between the ages of
      11-19 years. Participants completed a screening measure to assess occurrence of
      NSSI and its characteristics. Results indicate an overall lifetime prevalence of
      22.6% (n = 215), with significantly more males (26.98%, n = 129) than females
      (18.14%, n = 86) reporting having engaged in NSSI at least once in their
      lifetime. This study provides empirical evidence that adolescent engagement in
      NSSI occurs at similar prevalence levels in Jordan, relative to North American
      samples, whereas gender comparisons of prevalence and characteristics revealed
      several differences.

PMID- 25058811
TI  - A decision dilemma: Cushing syndrome during pregnancy.

PMID- 25058812
TI  - Optimized loudness-function estimation for categorical loudness scaling data.
AB  - Individual loudness perception can be assessed using categorical loudness scaling
      (CLS). The procedure does not require any training and is frequently used in
      clinics. The goal of this study was to investigate different methods of loudness
      function estimation from CLS data in terms of their test-retest behaviour and to
      suggest an improved method compared to Brand and Hohmann (2002) for adaptive CLS.
      Four different runs of the CLS procedure were conducted using 13 normal-hearing
      and 11 hearing-impaired listeners. The following approaches for loudness-function
      estimation (fitting) by minimising the error between the data and loudness
      function were compared: Errors were defined both in level and in loudness
      direction, respectively. The hearing threshold level (HTL) was extracted from CLS
      by splitting the responses into an audible and an inaudible category. The
      extracted HTL was used as a fixed starting point of the loudness function. The
      uncomfortable loudness level (UCL) was estimated if presentation levels were not
      sufficiently high to yield responses in the upper loudness range, as often
      observed in practise. Compared to the original fitting method, the modified
      estimation of the HTL was closer to the pure-tone audiometric threshold. Results
      of a computer simulation for UCL estimation showed that the estimation error was
      reduced for data sets with sparse or absent responses in the upper loudness
      range. Overall, the suggested modifications lead to a better test-retest
      behaviour. If CLS data are highly consistent over the whole loudness range, all
      fitting methods lead to almost equal loudness functions. A considerable advantage
      of the suggested fitting method is observed for data sets where the responses
      either show high standard deviations or where responses are not present in the
      upper loudness range. Both cases regularly occur in clinical practice. 

PMID- 25058813
TI  - Disorganization of the retinal inner layers as a predictor of visual acuity in
      eyes with center-involved diabetic macular edema.
AB  - IMPORTANCE: Biomarkers that predict future visual acuity (VA) in eyes with
      baseline diabetic macular edema (DME) would substantively improve risk
      assessment, management decisions, and selection of eyes for clinical studies
      targeting DME. OBJECTIVE: To determine whether baseline or early change in the
      novel spectral domain-optical coherence tomography (SD-OCT) parameter
      disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes
      with center-involved DME. DESIGN, SETTING, AND PARTICIPANTS: At a tertiary care
      referral center for diabetic eye disease, a retrospective, longitudinal cohort
      study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8
      month visits in 96 participants (120 eyes) with diabetes mellitus and baseline
      center-involved DME (SD-OCT central subfield thickness, >= 320 um for men and >=
      305 um for women). Exclusion criteria included substantial media opacity,
      cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA.
      On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by
      masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone
      outer segment tip visibility, and external limiting membrane or photoreceptor
      disruption and reflectivity. MAIN OUTCOMES AND MEASURES: Visual acuity and SD-OCT
      derived retinal morphology. RESULTS: Greater DRIL extent at baseline correlated
      with worse baseline VA (point estimate, 0.04; 95% CI, 0.02-0.05 per 100 um; P <
      .001). An increase in DRIL during 4 months was associated with VA worsening at 8
      months (point estimate, 0.03; 95% CI, 0.02-0.05 per 100 um; P < .001). A
      multivariate model that included a 4-month change in VA, DRIL, and external
      limiting membrane disruption was predictive of an 8-month VA change (r = 0.80).
      Each approximately 300-um DRIL increase during 4 months predicted a 1-line, 8
      month VA decline. When DRIL increased at least 250 um at 4 months, no eyes had VA
      improvement of at least 1 line at 8 months. When DRIL decreased at least 250 um
      at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7% had
      VA improvement of at least 1 line. CONCLUSIONS AND RELEVANCE: Disorganization of
      the retinal inner layers in the 1-mm foveal area is associated with VA, and
      change in DRIL predicts future change in VA. Early change in DRIL prospectively
      identifies eyes with a high likelihood of subsequent VA improvement or decline.
      Therefore, DRIL warrants further study as a robust, readily obtained, and
      noninvasive biomarker of future VA response in eyes with DME.

PMID- 25058814
TI  - Medical screening after a coal fly ash spill in Roane County, Tennessee.
AB  - OBJECTIVE: To assess the health of community residents following a coal fly ash
      spill at the Tennessee Valley Authority Kingston Fossil Plant in Harriman,
      Tennessee, on December 22, 2008. METHODS: A uniform health assessment was
      developed by epidemiologists at Oak Ridge Associated Universities and medical
      toxicologists at Vanderbilt University Medical Center. Residents who believed
      that their health may have been affected by the coal fly ash spill were invited
      to participate in the medical screening program. RESULTS: Among the 214
      individuals who participated in the screening program, the most commonly reported
      symptoms were related to upper airway irritation. No evidence of heavy metal
      toxicity was found. CONCLUSIONS: This is the first report, to our knowledge,
      regarding the comprehensive health evaluation of a community after a coal fly ash
      spill. Because this evaluation was voluntary, the majority of residents screened
      represented those with a high percentage of symptoms and concerns about the
      potential for toxic exposure. Based on known toxicity of the constituents present
      in the coal fly ash, health complaints did not appear to be related to the fly
      ash. This screening model could be used to assess immediate or baseline toxicity
      concerns after other disasters.

PMID- 25058815
TI  - Caffeine improves the efficiency of planning and sequencing abilities during
      sleep deprivation.

PMID- 25058816
TI  - Endoscopic resection of a giant pedunculated polyp using scissor-type forceps.

PMID- 25058817
TI  - Scurvy presenting as hematochezia.

PMID- 25058818
TI  - Percutaneous transhepatic biliojejunal rendezvous technique for biliary
      obstruction with Billroth II anatomy.

PMID- 25058819
TI  - Safe removal of an impacted stone retrieval basket during ERCP using a single
      balloon enteroscope in a patient with a Roux-en-Y gastrectomy.

PMID- 25058820
TI  - Gastrointestinal bleeding from jejunal heterotopic pancreas diagnosed by deep
      small-bowel enteroscopy.

PMID- 25058821
TI  - Catastrophic complication of ingestion of corrosive substance.

PMID- 25058822
TI  - Rendezvous technique using bronchoscopy and gastroscopy to close a
      tracheoesophageal fistula by placement of an over-the-scope clip.

PMID- 25058823
TI  - Atypical placement of the pylorus: a rare congenital abnormality.

PMID- 25058824
TI  - To twist or not to twist: a case of ERCP in situs inversus totalis.

PMID- 25058825
TI  - Migration of embolization coils placed to stop a severe iatrogenic bleed
      following endoscopic ultrasound-guided cystogastrostomy.

PMID- 25058826
TI  - Ipilimumab-induced colitis: a rare but serious side effect.

PMID- 25058827
TI  - An unusual duodenal polyp: Brunner's gland hyperplasia.

PMID- 25058828
TI  - Colonic NK/T-cell lymphoma mimicking Crohn's disease.

PMID- 25058829
TI  - Over-the-scope-clipping in colonic perforation caused small-bowel fixation and
      pneumoperitoneum requiring surgical repair.

PMID- 25058830
TI  - Extrahepatic bile duct duplication complicated by choledocholithiasis.

PMID- 25058831
TI  - Hydatid cyst mimicking cystic neoplasm of the pancreatic tail: an endoscopic
      ultrasound diagnosis.

PMID- 25058832
TI  - Agave biotechnology: an overview.
AB  - Agaves are plants of importance both in Mexican culture and economy and in other
      Latin-American countries. Mexico is reported to be the place of Agave origin,
      where today, scientists are looking for different industrial applications without
      compromising its sustainability and preserving the environment. To make it
      possible, a deep knowledge of all aspects involved in production process, agro
      ecological management and plant biochemistry and physiology is required. Agave
      biotechnology research has been focusing on bio-fuels, beverages, foods, fibers,
      saponins among others. In this review, we present the advances and challenges of
      Agave biotechnology. 

PMID- 25058833
TI  - Small cell neuroendocrine carcinoma of cervix and leiomyoma between the vagina
      and rectum.

PMID- 25058834
TI  - Evaluation of paraclinical tests in the diagnosis of cervicogenic dizziness.
AB  - OBJECTIVE: To assess the utility of the paraclinical tests in patients presenting
      with clinical diagnosis of cervicogenic dizziness. STUDY DESIGN: Case controlled.
      SETTING: Otolaryngology clinic of a tertiary referral hospital center. PATIENTS:
      Twenty-five subjects with cervicogenic dizziness and 25 subjects with benign
      paroxysmal positional vertigo. MAIN OUTCOME MEASURES: Symptoms description,
      Dizziness Handicap Inventory-short form (DHI), Trait anxiety score, cervical
      joint position error, the smooth pursuit neck torsion and cervical torsion tests
      on videonystagmography, and standing balance test (timed 10-meter walk with head
      turns). RESULTS: The results showed differences in reported symptoms, in mean
      cervical joint position error (p = 0.001), and cervical torsion test (p = 0.001)
      between the two groups. There was no between-group difference for DHI scores (p =
      0.137), trait anxiety scores (p = 0.240), and walking test: time (p = 0.797),
      steps (p = 0.963). The Youden index is 0.60 for the predictive value of the
      cervical joint position error, and the smooth pursuit and the cervical torsion
      tests. CONCLUSION: This study showed differences in sensorimotor disturbances
      between the two groups, particularly in the control of head and eye movements and
      cervical proprioception. Patients with cervicogenic dizziness were more likely to
      (1) have a sensation of drunkenness and lightheadedness, (2) have pain induced
      during the physical examination of the upper cervical vertebrae, (3) have an
      elevated joint position error of 4.5 degrees during the cervical relocation test,
      and (4) exhibit more than 2 degrees per second nystagmus during the cervical
      rotation test. The walking test was not able to differentiate the two groups.

PMID- 25058835
TI  - Methicillin-Resistant Staphylococcus aureus Otic Capsule and Pontine Infection
      Masquerading as an Internal Auditory Canal Neoplasm.

PMID- 25058836
TI  - Coregistration of preoperative computed tomography and intraoperative three
      dimensional rotational x-ray images for cochlear implant surgical evaluation.
AB  - OBJECTIVE: A registration procedure of intraoperative three-dimensional
      rotational x-ray (3DRX) imaging and preoperative computed tomography (CT) imaging
      so that intraoperative CT quality imaging is available during cochlear implant
      surgery, providing detailed information concerning electrode position in the
      cochlea and its relation to surrounding bony structures. STUDY DESIGN:
      Retrospective case series SETTING: Tertiary referral center DATA: The imaging of
      five patients who had undergone cochlear implant surgery is used to develop a
      semiautomatic registration procedure to integrate intraoperative 3DRX and
      preoperative CT. The method is implemented in advanced medical imaging software
      to compute the transformations. The electrode is segmented from the registered
      3DRX images using a semiautomated approach. The segmented electrode is
      superimposed onto the CT data. The methods are quantitatively validated based on
      expert-labeled anatomical landmarks. These landmarks are identified in the CT and
      3DRX images by an expert. MAIN OUTCOME MEASURE: Mean error of the registration
      procedure for five anatomical landmarks in millimeters. RESULTS: Quantitative
      analysis showed a mean error of between 0.5 and 1 mm for all anatomical
      landmarks, suggesting that the results are trustworthy. CONCLUSION: We developed
      a reliable procedure for the registration of intraoperative 3DRX imaging and
      preoperative CT imaging for cochlear implant surgery. This registration procedure
      provides the ENT surgeon intraoperative high-quality CT imaging during cochlear
      implant surgery.

PMID- 25058837
TI  - Lateral-to-malleus underlay tympanoplasty: surgical technique and outcomes.
AB  - OBJECTIVE: The lateral-to-malleus underlay tympanoplasty (LMUT) involves
      dissection of the tympanic membrane remnant from the malleus with subsequent
      graft placement medial to the annulus but lateral to the malleus. The objective
      of the current study is to describe the clinical outcomes using the LMUT
      technique. PATIENTS: One hundred forty-one ears undergoing LMUT. To isolate the
      effects of tympanoplasty on audiometric outcome, only cases with an intact and
      mobile ossicular chain were evaluated; ears with ossicular discontinuity,
      fixation, and/or ossicular chain reconstruction were excluded. INTERVENTION:
      Lateral-to-malleus underlay tympanoplasty. MAIN OUTCOME MEASURES: 1) Change in
      air-bone gap and bone conduction thresholds; 2) tympanic membrane lateralization;
      and 3) primary and delayed graft failure. RESULTS: One hundred forty-one
      tympanoplasties were analyzed. In the early postoperative period, 140 (99%) of
      141 grafts were intact and, at a mean of 32.1 months, 121 (85.8%) remained
      without significant retraction or reperforation. There were no cases of early or
      delayed graft lateralization. The mean preoperative and most recent postoperative
      air-bone gaps were 23.7 dB and 14.1 dB, respectively (p < 0.001). Surgery was not
      associated with a transient or long-term bone conduction threshold shift.
      CONCLUSION: The LMUT technique offers improved exposure of the tympanic space and
      a low rate of graft failure. The risks of sensorineural hearing loss with
      ossicular chain manipulation and tympanic membrane lateralization from graft
      placement lateral to the malleus are very low.

PMID- 25058838
TI  - Evaluation of the bimodal benefit in a large cohort of cochlear implant subjects
      using a contralateral hearing aid.
AB  - OBJECTIVE: To investigate the benefit of contralateral residual hearing in a
      large group of cochlear implant recipients with different degrees of residual
      hearing. PATIENTS: One hundred and forty-one adult patients (age in years: mean
      58.82, min 16.27, max 88.20) wearing a cochlear implant and a contralateral
      hearing aid, bimodal. INTERVENTION: Rehabilitative. MAIN OUTCOME MEASURES: All
      141 patients underwent speech perception testing in quiet and noise with cochlear
      implant (CI) alone, and with CI and hearing aid (HA). Additionally, pure-tone air
      conduction threshold levels were measured in all subjects. The bimodal benefit
      was analyzed and correlations to the hearing threshold for different audiometric
      frequencies were calculated. RESULTS: Comparison between the scores for CI alone
      and CI + HA showed statistically significant advantages (p < 0.0001) in all four
      tests. The benefit for sentences in noise to each individual patient showed a
      negative correlation with the hearing threshold level of 125 Hz and 250 Hz, using
      a linear regression analysis applying the Spearman's rho correlation coefficient
      (r = -0.32, -0.232), and a significant difference at p = 0.006, p = 0.007. The
      correlations involving speech understanding in sentences in noise, and the
      hearing level of 500 Hz and above, are not significant for the benefit obtained
      with a contralateral hearing aid. CONCLUSION: The benefit of combined electric
      and acoustic hearing in bimodally fitted subjects depends mainly on residual
      hearing in the low-frequency range below 500 Hz. For bimodal fitting to yield
      significant benefits, hearing loss in the contralateral ear should not exceed 80
      dB HL in the low frequencies.

PMID- 25058839
TI  - Facial nerve outcomes after middle fossa decompression for Bell's palsy.
AB  - OBJECTIVE: Evaluate the long-term outcomes of facial nerve decompression via the
      middle fossa approach for Bell's palsy patients with poor prognosis based on
      clinical and electrodiagnostic testing. STUDY DESIGN: Retrospective case series.
      SETTING: Tertiary-care, academic medical center. PATIENTS: Fourteen patients
      underwent surgical decompression for Bell's palsy within 14 days of symptom onset
      from 2000 to 2012. Surgical criteria included greater than 90% degeneration on
      ENoG testing and no voluntary EMG potentials. INTERVENTION: Middle cranial fossa
      (MCF) bony decompression of the facial nerve, including the meatal foramen,
      labyrinthine segment, and geniculate ganglion. MAIN OUTCOME MEASURES: Long-term
      facial function, hearing results, and surgical complications. RESULTS: After MCF
      decompression, 10 patients (71.4%) regained normal or near-normal facial function
      (House-Brackmann [HB] I or II) within 1 year after surgery, and 5 of those
      patients (35.7%) improved to HB I. The remaining 4 patients (28.6%) improved to
      HB III. Patients older than 60 years (n = 3) had an HB III outcome and did
      significantly worse than the younger-than-60-years group (p = 0.002). The
      difference in preoperative and postoperative pure tone average and word
      recognition score was 2.1 dB and 0.9%, respectively. There were no major
      complications. Minor, transient complications occurred in 22.2% of patients.
      CONCLUSION: In patients with severe Bell's palsy at risk for a poor facial nerve
      outcome, MCF decompression of the facial nerve within 14 days of symptom onset
      provides good facial nerve outcomes with minimal morbidity.

PMID- 25058840
TI  - Diameter of long process of incus for stapes prosthesis.

PMID- 25058841
TI  - Stability of risky driving from late adolescence to early adulthood.
AB  - This study examined the stability of risky driving behaviour from late
      adolescence to early adulthood among 823 young Australian drivers participating
      in an ongoing longitudinal study. This issue was explored by examining the
      stability of risky driving between the ages of 19-20 and 23-24 years (1) across
      the cohort and (2) among individuals. Focusing on cohort-wide trends, a modest
      reduction in the occurrence of speeding was observed across the sample between 19
      20 and 23-24 years. However, drink-driving increased markedly over this period,
      and driving without a seatbelt or helmet for part of a trip also rose. Rates of
      other risky driving behaviours remained relatively unchanged. With regard to
      trends among individuals, while a decrease was evident in the risky driving
      propensities of many who had been classified as moderate or high risky drivers at
      age 19-20, 48% of the former group, and 77% of the latter group, still exhibited
      risky driving tendencies at 23-24 years. Together, these findings suggest a fair
      degree of stability in risky driving from late adolescence to early adulthood
      among this sample of Australian youth, highlighting the continuing need for road
      safety initiatives targeting young drivers beyond their first years of licensure.

PMID- 25058842
TI  - Development of a short form of the driving anger expression inventory.
AB  - The present study developed a revised version of the driving anger expression
      inventory (25-items) and a short (15-item) version using data from 551 drivers.
      Split half factor analyses on both versions confirmed the original four factors;
      personal physical aggressive expression, use of a vehicle to express anger,
      verbal aggressive expression and adaptive/constructive expression. The two DAX
      versions were strongly correlated, demonstrating the suitability of both forms of
      the scale and the aggressive forms of expression were higher for drivers who
      reported initiating road rage interactions. Total aggressive expression was also
      higher for drivers who reported recent crash-related conditions, such as: loss of
      concentration, losing control of their vehicle, moving violations, near-misses
      and major crashes. The revised DAX and DAX-short provide shorter versions of the
      49-item DAX that can more easily be combined with other questionnaires and
      require smaller sample sizes to analyse. Further research is required to validate
      these tools among different samples and populations. 

PMID- 25058843
TI  - Performance of new thresholds of the Glasgow Blatchford score in managing
      patients with upper gastrointestinal bleeding.
AB  - BACKGROUND & AIMS: Upper gastrointestinal hemorrhage (UGIH) is a common cause of
      hospital admission. The Glasgow Blatchford score (GBS) is an accurate determinant
      of patients' risk for hospital-based intervention or death. Patients with a GBS
      of 0 are at low risk for poor outcome and could be managed as outpatients. Some
      investigators therefore have proposed extending the definition of low-risk
      patients by using a higher GBS cut-off value, possibly with an age adjustment. We
      compared 3 thresholds of the GBS and 2 age-adjusted modifications to identify the
      optimal cut-off value or modification. METHODS: We performed an observational
      study of 2305 consecutive patients presenting with UGIH at 4 centers (Scotland,
      England, Denmark, and New Zealand). The performance of each threshold and
      modification was evaluated based on sensitivity and specificity analyses, the
      proportion of low-risk patients identified, and outcomes of patients classified
      as low risk. RESULTS: There were differences in age (P = .0001), need for
      intervention (P < .0001), mortality (P < .015), and GBS (P = .0001) among sites.
      All systems identified low-risk patients with high levels of sensitivity (>97%).
      The GBS at cut-off values of <=1 and <=2, and both modifications, identified low
      risk patients with higher levels of specificity (40%-49%) than the GBS with a cut
      off value of 0 (22% specificity; P < .001). The GBS at a cut-off value of <=2 had
      the highest specificity, but 3% of patients classified as low-risk patients had
      adverse outcomes. All GBS cut-off values, and score modifications, had low levels
      of specificity when tested in New Zealand (2.5%-11%). CONCLUSIONS: A GBS cut-off
      value of <=1 and both GBS modifications identify almost twice as many low-risk
      patients with UGIH as a GBS at a cut-off value of 0. Implementing a protocol for
      outpatient management, based on one of these scores, could reduce hospital
      admissions by 15% to 20%.

PMID- 25058844
TI  - Evaluation of Fenton method and ozone-based processes for colour and organic
      matter removal from biologically pre-treated swine manure.
AB  - This work evaluates the efficiency of different advanced oxidation processes
      (Fenton method, O3, H2O2 and O3/H2O2) for removing total COD (TCOD) and colour
      from biologically pre-treated swine manure. The Fenton process with a dosage of
      100 mg L(-1) of Fe(2+) and 800 mg L(-1) of H2O2 resulted in about 78% TCOD and
      96% colour reductions at an initial pH=3 after a reaction time of 30 min.
      Coagulation, rather than oxidation process, was identified as a crucial mechanism
      for removing pollutants. Otherwise, single ozonation achieved only 27-30% TCOD
      and 53-88% colour removals for ozone dosages ranging between 0.7 and 4.3 g O3 h(
      1) at the original wastewater pH (pH=8.1) after 30 min reaction time. The
      combined treatment with O3/H2O2 at pH=8.1 did not produce any significant TCOD or
      colour reduction improvement. Therefore, direct reactions with ozone rather than
      radical reactions were elucidated as the main removal mechanisms in the ozone
      based processes. Finally, a rough estimation of the operational costs involved in
      each process was also performed to compare their economic feasibility. The
      findings suggested that the Fenton process was more suitable than ozonation for
      reducing TCOD and colour from the biologically pre-treated swine manure.

PMID- 25058845
TI  - Long-acting bronchodilators and arterial stiffness in patients with COPD: a
      comparison of fluticasone furoate/vilanterol with tiotropium.
AB  - BACKGROUND: Increased arterial stiffness as measured by aortic pulse wave
      velocity (aPWV) predicts cardiovascular events and mortality and is elevated in
      patients with COPD. Prior investigation suggests that a long-acting beta-agonist
      (LABA)/inhaled corticosteroid (ICS) lowers aPWV in patients with baseline aPWV >=
      11 m/s. This study compared the effect of the ICS/LABA fluticasone
      furoate/vilanterol (FF/VI), 100/25 MUg, delivered via the ELLIPTA dry powder
      inhaler, with tiotropium bromide (TIO), 18 MUg, on aPWV. METHODS: This
      multicenter, randomized, blinded, double-dummy, parallel-group, 12-week study
      compared FF/VI and TIO, both administered once daily. The primary end point was
      aPWV change from baseline at 12 weeks. Safety end points included adverse events
      (AEs), vital signs, and clinical laboratory tests. RESULTS: Two hundred fifty
      seven patients with COPD and aPWV >= 11 m/s were randomized; 87% had prior
      cardiovascular events and/or risk. The mean difference in aPWV between FF/VI and
      TIO at week 12 was not significant (P = .484). Because the study did not contain
      a placebo arm, a post hoc analysis was performed to show that both treatments
      lowered aPWV by an approximate difference of 1 m/s compared with baseline. The
      proportion of patients reporting AEs was similar with FF/VI (24%) and TIO (18%).
      There were no changes in clinical concern for vital signs or clinical laboratory
      tests. CONCLUSIONS: No differences on aPWV were observed between FF/VI and TIO.
      However, further studies with a placebo arm are required to establish
      definitively whether long-acting bronchodilators lower aPWV. Both treatments
      demonstrated an acceptable tolerability profile. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01395888; URL: www.clinicaltrials.gov.

PMID- 25058846
TI  - Nanocomplex based on biocompatible phospholipids and albumin for long-circulation
      applications.
AB  - Achieving long circulating delivery of nanoparticles (NPs) is important for
      efficient drug therapy, but it is difficult due largely to proteins adsorption
      (opsonization) or/and nonsufficient stability of NPs. In this present work, we
      aimed to address the above issues by constructing a phospholipid and BSA-based
      nanocomplex system, namely BSA-phospholipid NPs (BSA-PL-NPs). Combining sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, X-ray photoelectron
      spectroscopy and proteins adsorption property, we confirmed that some BSA
      molecules were fixed on the inner surface of BSA-PL-NPs via hydrophobic
      interactions and the others were located in the core area. This special
      configuration allowed BSA-PL-NPs to not only maintain the antiadsorption and low
      phagocytosis properties but also have the slow zero-order drug release and the
      enhanced nanostructure stability. Interestingly, we found that BSA-PL-NPs had no
      cytotoxicity to mouse L929 fibroblasts but could stimulate the cells' growth
      instead. In conclusion, BSA-PL-NPs have a great potential to be developed as a
      long-circulation drug delivery system, and the ready availability,
      biocompatibility and nontoxicity of phospholipids and albumin give this system
      great promise for practical use. 

PMID- 25058847
TI  - Aryl hydrocarbon receptor protein and Cyp1A1 gene induction by LPS and
      phenanthrene in Atlantic cod (Gadus morhua) head kidney cells.
AB  - The objective of this study was to evaluate interactions between environmental
      toxicants and cod immune cells during inflammation. Phenanthrene is abundant in
      plant oils (rapeseed, palm, and soya oil) as compared to fish oils, and
      consequently constitute an undesirable element in plant replacement diets in
      aquaculture. Phenanthrene was added to head kidney cell cultures, alone or
      together with LPS (lipopolysaccharide) or poly I: C (polyinosinic acid:
      polycytidylic acid), and the responses were evaluated in terms of protein and
      gene expression. The results showed that LPS, poly I: C or phenanthrene, added to
      the cultures separately, induced aryl hydrocarbon receptor (AhR) protein
      expression. Phenanthrene treatment in combination with LPS induced AhR protein
      expression and Cyp1A1 gene transcription, which not was observed combining poly
      I: C and phenanthrene. Phenanthrene exposure up regulated the transcription of
      common stress and detoxification enzymes like catalase, caspase 3 and glutathione
      S-transferase alfa 3 subunit B (GSTAB3), while LPS exposure alone or combined
      with phenanthrene down regulated GSTAB3 and catalase in cod leukocytes. It seems
      clear that immune regulation and phenanthrene induced signaling pathways
      interact; transcriptional down regulation of detoxification and antioxidant
      enzymes by LPS could indicate that combating bacterial infections is the number
      one priority in these cells, and that AhR and Cyp1A1 is somehow involved in this
      signaling cascade. LPS seems to affect the mitogen activated protein kinases
      (MAPKs) pathways (P-p38 and ERK1/2) thus modulating the AhR protein and Cyp1A1
      gene transcription, while phenanthrene possibly activates AhR by ligand binding. 

PMID- 25058849
TI  - A low calorie morning meal prevents the decline of hepatic glycogen stores: a
      pilot in vivo (13)C magnetic resonance study.
AB  - Previous studies have reported a meal-induced rise in hepatic glycogen stores
      from baseline levels following a fast and it is generally assumed that glycogen
      levels rise steadily following meals throughout the day. However, measurements
      are normally taken in conditions that are not typical of the Western breakfast,
      which is relatively carbohydrate rich with a lower calorific content than most
      experimental test meals. As such, little is known about the normal metabolic
      response to a realistic, low calorie morning meal. Therefore, the aim of this
      pilot study was to evaluate the effects of a low dose oral glucose intake on
      hepatic glycogen levels following an overnight fast in healthy subjects. Glycogen
      levels were monitored in vivo using (13)C Magnetic Resonance Spectroscopy at
      baseline and hourly for 4 hours following either a 50 g glucose drink (773 kJ) or
      a control drink (0 kJ) given over two different visits. During the control visit
      hepatic glycogen levels decreased throughout the experiment with statistically
      significant decreases from baseline at 190 minutes (P < 0.05) and 250 minutes (P
      < 0.05). By contrast, the low dose glucose intake maintained glycogen
      concentrations with no significant decrease from baseline over 4 hours. A
      comparison between visits revealed that mean glycogen concentrations were
      significantly greater during the glucose visit (control visit, AUC = 218 +/- 39
      mol L(-1) min(-1); glucose visit, AUC = 305 +/- 49 mol L(-1) min(-1); P < 0.05).
      Liver volume decreased significantly from baseline at 180 minutes (P < 0.05) post
      consumption in both groups, with no significant difference found between visits.
      Gastric content volumes were significantly higher for the glucose visit
      immediately following consumption (P < 0.001) and at 60 minutes (P = 0.007)
      indicating slower gastric emptying for the glucose compared with the control. In
      conclusion, following an overnight fast, a low dose oral glucose challenge
      prevents a reduction in hepatic glycogen content but does not increase it above
      fasted levels. 

PMID- 25058850
TI  - N-acetylcysteine and azithromycin affect the innate immune response in cystic
      fibrosis bronchial epithelial cells in vitro.
AB  - BACKGROUND AND OBJECTIVE: We have previously reported that N-acetylcysteine
      (NAC), ambroxol and azithromycin (AZM) (partially) correct the chloride efflux
      dysfunction in cystic fibrosis bronchial epithelial (CFBE) cells with the
      DeltaF508 homozygous mutation in vitro. METHODS: In the present paper, we further
      investigated possible immunomodulatory effects of these drugs on the regulation
      of the innate immune system by studying the expression of the cytosolic NOD-like
      receptors NLRC1 and NLRC2, and interleukin (IL)-6 production in CFBE cells.
      RESULTS: Under basal conditions, PCR and Western Blot data indicate that the
      NLRC2 receptor has a reduced expression in CF cells as compared to non-CF (16HBE)
      cells, but that the NLRC1 expression is the same in both cell lines. AZM
      significantly upregulated NLRC1 and NLRC2 while NAC upregulated only NLRC2
      receptor expression in CF cells. Reduced basal IL-6 production was found in CF
      cells as compared to non-CF cells. MDP (an NLRC2 agonist), NAC and AZM, but not
      Tri-DAP (an NLRC1 agonist), increased IL-6 production in CF cells, indicating
      that in CF cells IL-6 upregulation is independent of NLRC1, but involves the
      activation of NLRC2. CONCLUSION: Overall, the results indicate that NAC and AZM
      not only can correct the chloride efflux dysfunction but also have a weakly
      strengthening effect on the innate immune system.

PMID- 25058851
TI  - M13 virus-directed synthesis of nanostructured metal oxides for lithium-oxygen
      batteries.
AB  - Transition metal oxides are promising electrocatalysts for both water oxidations
      and metal-air batteries. Here, we report the virus-mediated synthesis of cobalt
      manganese oxide nanowires (NWs) to fabricate high capacity Li-O2 battery
      electrodes. Furthermore, we hybridized Ni nanoparticles (NPs) on bio Co3O4 NWs to
      improve the round trip efficiency as well as the cycle life of Li-O2 batteries.
      This biomolecular directed synthesis method is expected to provide a selection
      platform for future energy storage electrocatalysts. 

PMID- 25058848
TI  - A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in
      malaria parasites.
AB  - Isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway
      generates commercially important products and is a target for antimicrobial drug
      development. MEP pathway regulation is poorly understood in microorganisms. Here
      we employ a forward genetics approach to understand MEP pathway regulation in the
      malaria parasite, Plasmodium falciparum. The antimalarial fosmidomycin inhibits
      the MEP pathway enzyme deoxyxylulose 5-phosphate reductoisomerase (DXR).
      Fosmidomycin-resistant P. falciparum are enriched for changes in the
      PF3D7_1033400 locus (hereafter referred to as PfHAD1), encoding a homologue of
      haloacid dehalogenase (HAD)-like sugar phosphatases. We describe the structural
      basis for loss-of-function PfHAD1 alleles and find that PfHAD1 dephosphorylates a
      variety of sugar phosphates, including glycolytic intermediates. Loss of PfHAD1
      is required for fosmidomycin resistance. Parasites lacking PfHAD1 have increased
      MEP pathway metabolites, particularly the DXR substrate, deoxyxylulose 5
      phosphate. PfHAD1 therefore controls substrate availability to the MEP pathway.
      Because PfHAD1 has homologues in plants and bacteria, other HAD proteins may be
      MEP pathway regulators. 

PMID- 25058852
TI  - The surprisingly complex immune gene repertoire of a simple sponge, exemplified
      by the NLR genes: a capacity for specificity?
AB  - Most bacteria are not pathogenic to animals, and may instead serve beneficial
      functions. The requisite need for animals to differentiate between microbial
      friend and foe is likely borne from a deep evolutionary imperative to recognise
      self from non-self, a service ably provided by the innate immune system. Recent
      findings from an ancient lineage of simple animals - marine sponges - have
      revealed an unexpectedly large and diverse suite of genes belonging to one family
      of pattern recognition receptors, namely the NLR genes. Because NLRs can
      recognise a broad spectrum of microbial ligands, they may play a critical role in
      mediating the animal-bacterial crosstalk needed for sophisticated discrimination
      between microbes of various relationships. The building blocks for an advanced
      NLR-based immune specificity encoded in the genome of the coral reef sponge
      Amphimedon queenslandica may provide a specialisation and diversity of responses
      that equals, or even exceeds, that of vertebrate NLRs. 

PMID- 25058853
TI  - Fish viperin exerts a conserved antiviral function through RLR-triggered IFN
      signaling pathway.
AB  - Mammalian viperin is a typical interferon (IFN)-induced antiviral protein. Fish
      have viperin homologs; however, little is known about the expression regulation
      of fish viperins. In this study, we report the expression regulation and
      antiviral function of a fish viperin from crucian carp Carassius auratus during
      IFN response. Crucian carp viperin is induced at mRNA and protein levels by fish
      IFNs and IFN stimuli such as poly(I:C). Consistently, this gene promoter contains
      multiple transcription factor binding sites including IFN-stimulated response
      elements (ISRE) and IFN gamma activation sequences (GAS), and is activated by two
      types of fish IFNs and also by the intracellular and extracellular poly(I:C).
      Activation of crucian carp viperin promoter by the intracellular poly(I:C) is
      mediated by retinoic acid-inducing gene I (RIG-I)-like receptors (RLR)-triggered
      IFN signaling pathway, which is further verified by the findings that each
      signaling molecule of RLR pathway is able to induce the expression of crucian
      carp viperin at mRNA and protein levels. Finally, overexpression of crucian carp
      viperin in cultured fish cells confers significant protection against infection
      of grass carp reovirus (GCRV). These data suggest that similar to mammalian
      homologs, crucian carp viperin exerts a conserved function through RLR-triggered
      IFN signaling pathway. 

PMID- 25058854
TI  - Liver ischemia/reperfusion injury: an overview.
AB  - The present review discusses strategies for minimizing the ischemia/reperfusion
      injury (IRI) experienced during liver surgery and transplantation. We present the
      experimental models used to study the complexity of hepatic IRI and new surgical
      and pharmacologic strategies for manipulating and improving liver function after
      liver surgery and transplantation. This would be of clinical interest to reduce
      the prevalence of IRI and improve patient management and outcomes. The ongoing
      effort to expand the pool of usable liver grafts has made it clear that a better
      understanding of the mechanisms of IRI and other consequences of using expanded
      criteria donor (ECD) liver allografts are critical to improving results with
      these grafts.

PMID- 25058855
TI  - Use of animals for toxicology testing is necessary to ensure patient safety in
      pharmaceutical development.
AB  - There is an active debate in toxicology literature about the utility of animal
      testing vis-a-vis alternative in vitro paradigms. To provide a balanced
      perspective and add to this discourse it is important to review the current
      paradigms, explore pros and cons of alternatives, and provide a vision for the
      future. The fundamental goal of toxicity testing is to ensure safety in humans.
      In this article, IQ Consortium DruSafe, while submitting the view that
      nonclinical testing in animals is an important and critical component of the risk
      assessment paradigm in developing new drugs, also discusses its views on
      alternative approaches including a roadmap for what would be required to enhance
      the utilization of alternative approaches in the safety assessment process. 

PMID- 25058856
TI  - How tethers control the chemo- and regioselectivities of intramolecular
      cycloadditions between aryl-1-aza-2-azoniaallenes and alkenes.
AB  - Cationic 1-aza-2-azoniaallenes react intermolecularly with terminal alkenes to
      give 1,5-substituted (3 + 2)-cycloadducts, but intramolecular reactions lead to
      either 1,5- or 1,4-substituted (3 + 2)-cycloadducts or (4 + 2)-cycloadducts,
      depending on the tether length. DFT calculations and distortion/interaction
      analyses show that the (CH2)3 tether prevents the reacting partners from aligning
      efficiently to give 1,5-substituted (3 + 2)-cycloadducts, and the 1,4
      regioselectivity dominates. With the (CH2)2 tether, the (3 + 2) cycloaddition is
      disfavored due to the forming four-membered ring in the transition state, and the
      (4 + 2) cycloaddition prevails. 

PMID- 25058857
TI  - Folate-conjugated beta-cyclodextrin-based polymeric micelles with enhanced
      doxorubicin antitumor efficacy.
AB  - In order to enhance the antitumor effects of doxorubicin (DOX), a novel micellar
      vector with high DOX loading and tumor targeting function based on folate
      conjugated amphiphilic copolymer folate-poly(ethylene glycol)-poly(d,l-lactide)
      beta-cyclodextrin (FA-PEL-CD) was constructed. Cytotoxicity and cellular uptake
      experiments were performed in HeLa, KB, and A549 cell lines expressing different
      amounts of folate receptors in order to evaluate the targeting effect of the
      folate modification. The antitumor experiments performed in a KB cell-xenografted
      nude mouse model showed that the treatment with 10mg/kg DOX loaded FA-PEL-CD
      micelles achieved approximately 86% of tumor growth inhibition compared to the
      control. Ex vivo fluorescence imaging experiments and histological examination
      confirmed that folate modification can enhance the antitumorigenesis efficacy and
      reduce the cardiotoxicity of DOX. These results suggest that FA-PEL-CD copolymer
      based micelles are promising nanocarriers for targeted doxorubicin delivery, with
      improved antitumor efficacy and reduced toxicity in normal tissues. 

PMID- 25058858
TI  - Split and flow: reconfigurable capillary connection for digital microfluidic
      devices.
AB  - Supplying liquid to droplet-based microfluidic microsystems remains a delicate
      task facing the problems of coupling continuous to digital or macro- to
      microfluidic systems. Here, we take advantage of superhydrophobic microgrids to
      address this problem. Insertion of a capillary tube inside a microgrid aperture
      leads to a simple and reconfigurable droplet generation setup. 

PMID- 25058859
TI  - Motility and fertilization ability of sterlet Acipenser ruthenus testicular sperm
      after cryopreservation.
AB  - Sturgeon spermatozoa are immotile in the testis and acquire the potential for
      motility after contact with urine in Wolffian duct. The present study tested if
      in vitro incubation of testicular sperm in seminal fluid from Wolffian duct sperm
      leads to the acquisition of sperm fertilization ability. Sterlet sperm was taken
      from the testes, matured in vitro and cryopreserved. The fertility and motility
      of cryopreserved semen were tested. Matured testicular sperm showed freeze-thaw
      survival rates similar to Wolffian duct sperm, which is commonly used in sturgeon
      artificial propagation. Matured testicular sperm and Wolffian duct sperm post
      thaw motility rate and curvilinear velocity were not significantly different,
      while duration of matured testicular sperm motility was significantly shorter
      than that of Wolffian duct sperm. Development rates of embryos obtained with post
      thaw matured testicular sperm and Wolffian duct sperm were not significantly
      different. In vitro maturation of sterlet testicular sperm can potentially be
      useful in sperm cryobanking.

PMID- 25058861
TI  - Effect of lithiation potential and cycling on chemical and morphological
      evolution of Si thin film electrode studied by ToF-SIMS.
AB  - Si thin films obtained by plasma enhanced chemical vapor deposition (PECVD) were
      used to investigate chemical and morphological modifications induced by
      lithiation potential and cycling. These modifications were thoughtfully analyzed
      by time-of-flight secondary ion mass spectrometry (ToF-SIMS) depth profiling,
      which allows to distinguish the surface and bulk processes related to the
      formation of the solid electrolyte interphase (SEI) layer, and Li-Si alloying,
      respectively. The main results are a volume expansion/shrinkage and a dynamic
      behavior of the SEI layer during the single lithiation/delithiation process and
      multicycling. Trapping of lithium and other ions corresponding to products of
      electrolyte decomposition are the major reasons of electrode modifications. It is
      shown that the SEI layer contributes to 60% of the total volume variation of Si
      electrodes (100 nm). The apparent diffusion coefficient of lithium (DLi)
      calculated from the Fick's second law directly from Li-ion ToF-SIMS profiles is
      of the order of ~5.9 * 10(-15) cm(2).s(-1). This quite low value can be explained
      by Li trapping in the bulk of electrode material, at the interfaces, continuous
      growth of the SEI layer and increase of SiO2 quantity. These modifications can
      result in limitation the ionic transport of Li. 

PMID- 25058862
TI  - Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative
      patients.
AB  - BACKGROUND: Pneumocystis jiroveci pneumonia in human immunodeficiency virus (HIV)
      negative immunocompromised patients is associated with high mortality rates.
      Although trimethoprim-sulfamethoxazole provides a very effective prophylaxis,
      pneumocystosis still occurs and may even be emerging due to suboptimal
      characterization of patients most at risk, hence precluding targeted prophylaxis.
      METHODS: We retrospectively analyzed all cases of documented pneumocystosis in
      HIV-negative patients admitted in our institution, a referral center in the area,
      from January 1990 to June 2010, and extracted data on their underlying
      condition(s). To estimate incidence rates within each condition, we estimated the
      number of patients followed-up in our area for each condition by measuring the
      number of patients admitted with the corresponding international classification
      diagnostic code, through the national hospital discharge database (Program of
      Medicalization of the Information System [PMSI]). RESULTS: From 1990 to 2010, 293
      cases of pneumocystosis were documented, of which 154 (52.6%) tested negative for
      HIV. The main underlying conditions were hematological malignancies (32.5%),
      solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant
      (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in 3
      categories: 1) high risk (incidence rates >45 cases per 100,000 patient-year):
      polyarteritis nodosa, granulomatosis with polyangiitis,
      polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia,
      and non-Hodgkin lymphoma; 2) intermediate risk (25-45 cases per 100,000 patient
      year): Waldenstrom macroglobulinemia, multiple myeloma, and central nervous
      system cancer; and 3) low risk (<25 cases per 100,000 patient-year): other solid
      tumors, inflammatory diseases, and Hodgkin lymphoma. CONCLUSIONS: These estimates
      may be used as a guide to better target pneumocystosis prophylaxis in the groups
      most at risk.

PMID- 25058863
TI  - History of thyroid disorders in relation to clinical outcomes in atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common cardiac complication of
      hyperthyroidism. The association between history of hyperthyroidism and stroke
      remains unclear. We sought to determine whether history of thyroid dysfunction is
      a thromboembolic risk factor in patients with atrial fibrillation. METHODS:
      Patients with atrial fibrillation seen in an academic institution between 2000
      and 2010 were identified and followed-up. Clinical events (stroke/systemic
      embolism, bleeding, all-cause death) were recorded and related to thyroid status
      and disorders. Associations were examined in time-dependent models with
      adjustment for relevant confounders. RESULTS: Among 8962 patients, 141 patients
      had a history of hyperthyroidism, 540 had a history of hypothyroidism, and 8271
      had no thyroid dysfunction. Mean follow-up was 929 +/- 1082 days. A total of 715
      strokes/systemic embolism were recorded, with no significant difference in the
      rates of these events in patients with a history of thyroid dysfunction vs those
      without thyroid problems in either univariate or multivariable analysis (hazard
      ratio [HR] 0.85; 95% confidence interval [CI], 0.41-1.76 for hyperthyroidism; HR
      0.98; 95% CI, 0.73-1.34 for hypothyroidism). There were 791 bleeding events;
      history of hypothyroidism was independently related to a higher rate of bleeding
      events (HR 1.35; 95% CI, 1.02-1.79). No significant difference among the 3 groups
      was observed for the incidence of death. CONCLUSIONS: History of hyperthyroidism
      was not an independent risk factor for stroke/systemic embolism in atrial
      fibrillation, whereas hypothyroidism was associated with a higher risk of
      bleeding events. These data suggest no additional benefit from the inclusion of
      thyroid dysfunction in thromboembolic prediction models in atrial fibrillation.

PMID- 25058865
TI  - Posttraumatic intrathoracic splenosis: from clinical suspicion to noninvasive
      diagnosis.

PMID- 25058864
TI  - Early repolarization masquerading as STEMI.

PMID- 25058866
TI  - A rare concurrence: nonischemic cardiomyopathy and multiple myeloma without
      amyloidosis.

PMID- 25058867
TI  - Angiotensin-converting enzyme inhibitor-induced angioedema.
AB  - Angiotensin-converting enzyme inhibitors (ACE-I) are widely used, effective, and
      well-tolerated antihypertensive agents. The mechanisms by which those agents act
      can cause side effects such as decreased blood pressure, hyperkalemia, and
      impaired renal function. ACE-I can induce cough in 5%-35% and angioedema in up to
      0.7% of treated patients. Because cough and angioedema are considered class
      adverse effects, switching treatment to other ACE-I agents is not recommended.
      Angioedema due to ACE-I has a low fatality rate, although deaths have been
      reported when the angioedema involves the airways. Here, we review the role of
      bradykinin in the development of angioedema in patients treated with ACE-I, as
      well as the incidence, risk factors, clinical presentation, and available
      treatments for ACE-I-induced angioedema. We also discuss the risk for recurrence
      of angioedema after switching from ACE-I to angiotensin receptor blockers
      treatment. 

PMID- 25058868
TI  - Antegrade venography identifies parallel venous duplications in the majority of
      adolescents with varicocele.
AB  - PURPOSE: We performed intraoperative antegrade venography to assess the
      prevalence of internal spermatic venous malformations in adolescents with
      varicocele. MATERIALS AND METHODS: During a 2-year period 58 adolescent males
      with visible or palpable varicocele underwent antegrade venography before
      varicocele surgery. Antegrade venography was performed through a scrotal
      incision. A vein within the pampiniform plexus was cannulated and up to 1.75
      mg/kg iohexol 300 mg/ml was injected to outline the entire length of the internal
      spermatic vein. The radiographs were reviewed and classified according to Bahren
      and Murray criteria. RESULTS: Of the patients 43 (74.1%) demonstrated parallel
      duplications (Murray classification type P) of the internal spermatic vein. This
      rate is higher than the 2% reported based on retrograde venography. Of the
      patients with parallel duplications 21 (48.8%) showed duplications arising
      superior to the iliac crest (subtype A) and 22 (51.2%) had a combination of
      proximal duplications (subtypes B and C). Ten patients (17.2%) had a single
      internal spermatic vein, 2 (3.4%) had lumbar collaterals and 3 (5.2%) had renal
      collaterals. CONCLUSIONS: Parallel duplication of the internal spermatic vein is
      a common finding on antegrade venography. The various levels of duplication need
      to be identified before treatment of varicocele to maximize the success of the
      procedure.

PMID- 25058869
TI  - Implications of stillage land disposal: a critical review on the impacts of
      fertigation.
AB  - Stillage is the main wastewater from ethanol production, generated specifically
      in the step of distillation. Regardless the feedstock, stillage contains high
      concentrations of organic matter, potassium and sulfates, as well as acidic and
      corrosive characteristics. Currently almost the entire volume of stillage
      generated in Brazilian distilleries is directed to the fertigation of sugarcane
      fields, due to its fertilizer character. However, the polluting potential of
      stillage characterizes its land disposal as problematic, considering probable
      negative impacts on the soil structure and water resources in case of excessive
      dosages. Since the literature lacks critical content describing clearly the cons
      related to the reuse of stillage in agriculture in the long-term, this review
      aimed to assess the real polluting potential of stillage, and the implications of
      its land disposal and/or discharge into water bodies. Evidence from the
      literature indicate that the main obstacles to reuse stillage in natura include
      risks of soil salinization; clogging of pores, reduction in the microbial
      activity and the significant depletion of dissolved oxygen concentrations in
      water bodies; contamination per nitrates and eutrophication; soil structure
      destabilization due to high concentrations of potassium and sodium; and, possible
      acidification of soil and water resources, considering the low pH of stillage
      (~4,5). Toxic metals, such as cadmium, lead, copper, chromium and nickel, were
      also identified in concentrations above the recommended limits in stillage
      samples, increasing risks to human health (e.g. carcinogenic potential) and to
      crops (e.g. productivity loss). In short, although some studies report benefits
      from the land application of stillage, its treatment prior to disposal is
      essential to make fertigation an environmentally suitable practice. 

PMID- 25058871
TI  - Interferon-alpha2b against microbes through promoting biosynthesis of unsaturated
      fatty acids.
AB  - Interferon (IFN) family is a large group of cytokines involved in innate immune
      response against various microorganisms. However, whether IFN functions in
      antimicrobial property by metabolic pathways is largely unknown. In the present
      study, GC-MS-based metabolome is investigated in humoral fluid of zebrafish
      (Danio rerio) which are exposed to three doses of IFN-alpha2b, designed as IFN-L,
      IFN-M, and IFN-H. Out of 67 compounds identified, 19, 28, and 29 differential
      abundances of metabolites are identified in the three groups compared with
      control, respectively. A total of 41 differential metabolites constructed IFN
      dependent metabolome, in which 13 overlap among the three doses of IFN-alpha2b
      groups. These overlapped metabolites show that decreased alanine asparate and
      glutamate metabolic pathway, arginine and proline metabolic pathway, and
      increased purine metabolism form a characteristic feature in response to IFN
      alpha2b. Further dose-related metabolites indicate that biosynthesis of
      unsaturated fatty acids is enriched only in IFN-M and IFN-H, which is related to
      high protection against bacterial infection. Exogenous fatty acids, especially
      unsaturated linoleic acid, may elevate the survival ability of zebrafish infected
      with extracellular pathogenic V. alginolyticus and intracellular pathogenic
      Edwardsiella tarda. These results disclose an unknown mechanism by which IFN
      alpha2b protects host from microbial infections. Our findings highlight the ways
      to understand action of IFN in content of metabolic regulation. 

PMID- 25058870
TI  - Quantifying the length and variance of the eukaryotic cell cycle phases by a
      stochastic model and dual nucleoside pulse labelling.
AB  - A fundamental property of cell populations is their growth rate as well as the
      time needed for cell division and its variance. The eukaryotic cell cycle
      progresses in an ordered sequence through the phases G1, S, G2, and M, and is
      regulated by environmental cues and by intracellular checkpoints. Reflecting this
      regulatory complexity, the length of each phase varies considerably in different
      kinds of cells but also among genetically and morphologically indistinguishable
      cells. This article addresses the question of how to describe and quantify the
      mean and variance of the cell cycle phase lengths. A phase-resolved cell cycle
      model is introduced assuming that phase completion times are distributed as
      delayed exponential functions, capturing the observations that each realization
      of a cycle phase is variable in length and requires a minimal time. In this
      model, the total cell cycle length is distributed as a delayed hypoexponential
      function that closely reproduces empirical distributions. Analytic solutions are
      derived for the proportions of cells in each cycle phase in a population growing
      under balanced growth and under specific non-stationary conditions. These
      solutions are then adapted to describe conventional cell cycle kinetic assays
      based on pulse labelling with nucleoside analogs. The model fits well to data
      obtained with two distinct proliferating cell lines labelled with a single
      bromodeoxiuridine pulse. However, whereas mean lengths are precisely estimated
      for all phases, the respective variances remain uncertain. To overcome this
      limitation, a redesigned experimental protocol is derived and validated in
      silico. The novelty is the timing of two consecutive pulses with distinct
      nucleosides that enables accurate and precise estimation of both the mean and the
      variance of the length of all phases. The proposed methodology to quantify the
      phase length distributions gives results potentially equivalent to those obtained
      with modern phase-specific biosensor-based fluorescent imaging.

PMID- 25058872
TI  - Structural characterization of the C3 domain of cardiac myosin binding protein C
      and its hypertrophic cardiomyopathy-related R502W mutant.
AB  - Human cardiac myosin binding protein C (cMyBP-C), a thick filament protein found
      within the sarcomere of cardiac muscle, regulates muscle contraction and is
      essential for proper muscle function. Hypertrophic cardiomyopathy (HCM), a
      genetic disease affecting 1 in 500 people, is the major cause of death in young
      athletes. It is caused by genetic mutations within sarcomeric proteins. Forty-two
      percent of the HCM-related mutations are found in cMyBP-C. Here we present the
      nuclear magnetic resonance-derived structural ensembles of the wild-type cMyBP-C
      C3 domain and its HCM-related R502W mutant. The C3 domain adopts an
      immunoglobulin-like fold, and mutation of the exposed Arg502 to a tryptophan does
      not perturb its structure, dynamics, or stability. However, the R502W mutation
      does alter the predicted electrostatic properties of the C3 domain. We
      hypothesize that this mutation, and other HCM-linked mutations found within the
      same domain, may directly disrupt the interaction of cMyBP-C with other
      sarcomeric proteins. 

PMID- 25058873
TI  - Constructing the Suicide Risk Index (SRI): does it work in predicting suicidal
      behavior in young adults mediated by proximal factors?
AB  - Suicide is a key concern among young adults. The aim of the study was to (1)
      construct a suicide risk index (SRI) based on demographic, situational, and
      behavioral factors known to be linked to suicidal behavior and (2) investigate
      whether the association between the SRI and suicidal behavior was mediated by
      proximal processes (personal factors, coping strategies, and emotional states).
      Participants consisted of 7,558 individuals aged 17-25 years (M = 20.35, SD =
      1.91). Nearly 22% (n = 1,542) reported self-harm and 7% (n = 499) had attempted
      suicide. Mediation analysis revealed both a direct effect (beta = .299, 95% CI =
      [.281, .317], p < .001), and a mediated effect (beta = .204, 95% CI = [.186,
      .222], p < .001), between the risk index and suicidal behavior. The strongest
      mediators were levels of self-esteem, depression, and avoidant coping.
      Interventions to increase self-esteem, reduce depression, and encourage adaptive
      coping strategies may prevent suicidal behavior in young people.

PMID- 25058874
TI  - Ethnobotanical survey of usage of fresh medicinal plants in Singapore.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The use of medicinal plants in human health has
      been documented since ancient times and they provide a useful source of new
      therapeutics. In Singapore, despite the accessibility to modern healthcare, there
      still exist pockets of the population who choose to use locally grown fresh
      medicinal plants for health promotion and even therapeutic purposes. However to
      date, there is no published report of first-hand account of their usage in
      Singapore. As land is scarce and rapidly used for re-development, such important
      knowledge may be lost if not properly documented in time. This work safeguards
      the local folk knowledge, and provides information on common and scarcely
      reported fresh medicinal plants. The objective of this study is to gather
      information regarding the usage of fresh medicinal plants in Singapore through
      face-to-face interviews. MATERIALS AND METHODS: Information on demographic data
      and plant-use methods were collated via face-to-face interviews of 200 fresh
      medicinal plant users who have used fresh medicinal plants in the last five
      years. The survey protocol was approved by the National University of Singapore
      Institutional Review Board and informed consent was obtained from every
      participant. RESULTS: A total of 414 plants represented by 104 plant species from
      44 families were reportedly used by the 200 participants. The five most commonly
      used plants were Clinacanthus nutans (34 users), Strobilanthes crispus (31
      users), Pereskia bleo (25 users), Aloe vera (18 users) and Zingiber officinale
      (16 users). Leaves were the most commonly used plant part while preparing a
      decoction was the most common method of preparation. The majority of interviewees
      used plants for general health purposes and to treat diseases related to the
      respiratory system and cancer. CONCLUSIONS: Our survey has successfully
      documented the rich wealth of traditional usage and knowledge on 414 fresh
      medicinal plants grown in Singapore through face-to-face interviews with 200
      users. This study will serve as a useful resource for identifying promising
      plants for future drug discovery efforts. Scientific evaluations of these
      medicinal plants are warranted and should be carried out.

PMID- 25058875
TI  - In vitro antitrypanosomal and antiplasmodial activities of crude extracts and
      essential oils of Ocimum gratissimum Linn from Benin and influence of vegetative
      stage.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of Ocimum gratissimum Linn are
      largely used in folk medicine for the treatment of many diseases, some of which
      related to parasitical infections as fevers and headaches. In order to validate
      their use and to clarify the plant part which possesses the best antiparasitic
      properties, we decided to evaluate the in vitro antiplasmodial and
      antitrypanosomal activities of essential oils and crude extracts from leaves,
      stems and seeds of Ocimum gratissimum as well as their cytotoxicity. MATERIALS
      AND METHODS: The essential oils and ethanol crude extracts of leaves and stems of
      Ocimum gratissimum from Benin, were obtained in pre and full flowering stages.
      Seeds obtained only in full flowering stage, were also extracted. The oils were
      isolated by hydrodistillation and analyzed by GC/MS and GC/FID. Extracts and
      essential oils were tested in vitro against Trypanosoma brucei brucei and
      Plasmodium falciparum. Cytotoxicity was evaluated in vitro against Chinese
      Hamster Ovary (CHO) cells and the human non cancer fibroblast cell line (WI38)
      through MTT assay to evaluate the selectivity and toxicity was assessed against
      Artemia salina Leach. RESULTS: The essential oils and non-volatile crude extracts
      of Ocimum gratissimum were more active on Trypanosoma brucei brucei than on
      Plasmodium falciparum (3D7). This activity varies according to the vegetative
      stage (pre and full flowering) and the plant part (seeds, stems and leaves)
      extracted. The best growth inhibition of Trypanosoma brucei brucei was observed
      with ethanol crude extracts of leaves (IC50=1.66 +/- 0.48 MUg/mL) and seeds
      (IC50=1.29 +/- 0.42 MUg/mL) in full flowering stage with good selectivity
      (SI>10). The chemical composition of the essential oil from aerial parts (47
      compounds), characterized by the presence as main constituents of p-cymene,
      thymol, gamma-terpinene, beta-myrcene and alpha-thujene, depends on the
      vegetative stage. The oil contained some minor compounds such as myrcene
      (IC50=2.24 +/- 0.27MUg/mL), citronellal (IC50=2.76 +/- 1.55MUg/mL), limonene
      (IC50=4.24 +/- 2.27MUg/mL), with good antitrypanosomal activities. These oils and
      crude extracts were not toxic against Artemia salina Leach and had a low
      cytotoxicity except leaves and seeds ethanol extracts obtained in full flowering
      which showed toxicity against CHO and WI38 cells. CONCLUSIONS: Our study shows
      that ethanol crude extracts of leaves and seeds of Ocimum gratissimum in full
      flowering stage can be a good source of antitrypanosomal agents. This is the
      first report about the relation between the plant part extracted, the vegetative
      stage of the plant, the antitrypanosomal and antiplasmodial activities and the
      cytotoxicity of essential oils and non-volatile extracts of Ocimum gratissimum
      from Benin.

PMID- 25058876
TI  - The ForeSeeHome device and the HOME study: a milestone in the self-detection of
      neovascular age-related macular degeneration.

PMID- 25058877
TI  - A critical appraisal of the process of regulatory implementation of novel in vivo
      and in vitro methods for chemical hazard and risk assessment.
AB  - Regulatory toxicology urgently needs applicable alternative test systems that
      reduce animal use, testing time, and cost. European regulation on cosmetic
      ingredients has already banned animal experimentation for hazard identification,
      and public awareness drives toward additional restrictions in other regulatory
      frameworks as well. In addition, scientific progress stimulates a more
      mechanistic approach of hazard identification. Nevertheless, the implementation
      of alternative methods is lagging far behind their development. In search for
      general bottlenecks for the implementation of alternative methods, this
      manuscript reviews the state of the art as to the development and implementation
      of 10 diverse test systems in various areas of toxicological hazard assessment.
      They vary widely in complexity and regulatory acceptance status. The assays are
      reviewed as to parameters assessed, biological system involved, standardization,
      interpretation of results, extrapolation to human hazard, position in testing
      strategies, and current regulatory acceptance status. Given the diversity of
      alternative methods in many aspects, no common bottlenecks could be identified
      that hamper implementation of individual alternative assays in general. However,
      specific issues for the regulatory acceptance and application were identified for
      each assay. Acceptance of one-in-one replacement of complex in vivo tests by
      relatively simple in vitro assays is not feasible. Rather, innovative approaches
      using test batteries are required together with metabolic information and in
      vitro to in vivo dose extrapolation to convincingly provide the same level of
      information of current in vivo tests. A mechanistically based alternative
      approach using the Adverse Outcome Pathway concept could stimulate further
      (regulatory) acceptance of non-animal tests.

PMID- 25058878
TI  - Chemistry and multibeneficial bioactivities of carvacrol (4-isopropyl-2
      methylphenol), a component of essential oils produced by aromatic plants and
      spices.
AB  - Aromatic plants produce organic compounds that may be involved in the defense of
      plants against phytopathogenic insects, bacteria, fungi, and viruses. One of
      these compounds, called carvacrol, which is found in high concentrations in
      essential oils such as oregano, has been reported to exhibit numerous
      bioactivities in cells and animals. This integrated overview surveys and
      interprets our present knowledge of the chemistry and analysis of carvacrol and
      its beneficial bioactivities. These activities include its antioxidative
      properties in food (e.g., lard, sunflower oil) and in vivo and the inhibition of
      foodborne and human antibiotic-susceptible and antibiotic-resistant pathogenic
      bacteria, viruses, pathogenic fungi and parasites, and insects in vitro and in
      human foods (e.g., apple juice, eggs, leafy greens, meat and poultry products,
      milk, oysters) and food animal feeds and wastes. Also covered are inhibitions of
      microbial and fungal toxin production and the anti-inflammatory, analgesic,
      antiarthritic, antiallergic, anticarcinogenic, antidiabetic, cardioprotective,
      gastroprotective, hepatoprotective, and neuroprotective properties of carvacrol
      as well as metabolic, synergistic, and mechanistic aspects. Areas for future
      research are also suggested. The collated information and suggested research
      might contribute to a better understanding of agronomical, biosynthetic,
      chemical, physiological, and cellular mechanisms of the described health
      promoting effects of carvacrol, and facilitate and guide further studies needed
      to optimize the use of carvacrol as a multifunctional food in pure and
      encapsulated forms, in edible antimicrobial films, and in combination with plant
      derived and medical antibiotics to help prevent or treat animal and human
      diseases. 

PMID- 25058879
TI  - Pancreatic ductal perfusion at organ procurement enhances islet yield in human
      islet isolation.
AB  - OBJECTIVE: Pancreas preservation is a major factor influencing the results of
      islet cell transplantation. This study evaluated the effects of 2 different
      solutions for pancreatic ductal perfusion (PDP) at organ procurement. METHODS:
      Eighteen human pancreases were assigned to 3 groups: non-PDP (control), PDP with
      ET-Kyoto solution, and PDP with cold storage/purification stock solution.
      Pancreatic islets were isolated according to the modified Ricordi method.
      RESULTS: No significant differences in donor characteristics, including cold
      ischemia time, were observed between the 3 groups. All islet isolations in the
      PDP groups had more than 400,000 islet equivalence in total islet yield after
      purification, a significant increase when compared with the control (P = 0.04 and
      P < 0.01). The islet quality assessments, including an in vivo diabetic nude mice
      assay and the response of high-mobility group box protein 1 to cytokine
      stimulation, also showed no significant differences. The proportion of terminal
      deoxynucleotidyl transferase dUTP nick-end labeling-positive cells showing
      apoptosis in islets in the PDP groups was significantly lower than in the control
      group (P < 0.05). CONCLUSIONS: Both ET-Kyoto solution and cold
      storage/purification stock solution are suitable for PDP and consistently
      resulted in isolation success. Further studies with a larger number of pancreas
      donors should be done to compare the effects of the PDP solutions.

PMID- 25058881
TI  - DNA mismatch repair abnormalities in acinar cell carcinoma of the pancreas:
      frequency and clinical significance.
AB  - OBJECTIVES: Acinar cell carcinoma (ACC), including its mixed variants, is a rare
      pancreatic malignancy. Recent reports have documented its occurrence in Lynch
      syndrome. Our aim was to evaluate the frequency and clinicopathologic
      significance of DNA mismatch repair (MMR) deficiency in ACCs in general. METHODS:
      Mismatch repair protein expression was evaluated by immunohistochemistry in a
      series of 36 ACC cases that were treated at our institution and had sufficient
      clinical information and pathologic material. RESULTS: Loss of MMR protein was
      observed in 5 ACCs (5/36, 14%): 2 lost MLH1/PMS2, 2 lost MSH2/MSH6, and 1 lost
      MSH6 alone. The 1 MSH6-deficient case and 1 of the 2 MSH2/MSH6-deficient cases
      had a known history of Lynch syndrome, carrying a germline mutation in MSH6 and
      MSH2, respectively. None of the 5 tumors showed distinctive morphology. Two of
      the 5 patients died of disease 6 and 21 months after diagnosis. In contrast, in
      the MMR-normal group, only 1 of 30 patients died of disease (median follow-up,
      32.5 months). CONCLUSIONS: Mismatch repair protein deficiency is not uncommon in
      ACCs, occurring in 14% of the cases in this series. The MMR-deficient ACCs did
      not show distinctive morphologic features and were clinically no less aggressive
      than MMR-normal ACCs.

PMID- 25058880
TI  - Expression of estrogen-induced genes and estrogen receptor beta in pancreatic
      neuroendocrine tumors: implications for targeted therapy.
AB  - OBJECTIVE: The indolent nature and expression of progesterone receptor (PR), a
      well-known estrogen-induced gene, in a subset of pancreatic neuroendocrine tumors
      (PanNETs), raise the possibility of hormonal regulation in these tumors. METHODS:
      Immunohistochemical expression of estrogen receptors (ERs) alpha and beta as well
      as messenger RNA expression of estrogen-induced genes (PR, EIG121, IGF-1, IGF-1R,
      sFRP1, and sFRP4) by quantitative reverse transcription-polymerase chain reaction
      were examined in 131 World Health Organization grade G1 and G2 PanNETs and
      correlated their expression with clinicopathological features. RESULTS: Thirty
      nine PanNETs (30%) showed high positive ERbeta staining, and 87 cases (66%) had
      low positive ERbeta staining; only 5 cases (4%) had no nuclear staining.
      Pancreatic neuroendocrine tumors with small size (P = 0.02), low World Health
      Organization grade (P = 0.02), and low American Joint Committee on Cancer stage
      (P = 0.006) more frequently showed high positive ERbeta staining. Among the
      estrogen-induced genes studied, PanNETs had significantly higher expression of
      PR, EIG121, IGF-1, sFRP1, and sFRP4 compared with normal pancreas, independent of
      age or sex. High positive ERbeta staining was associated with an increased
      expression of PR (P < 0.001) and EIG121 (P = 0.02). CONCLUSIONS: Our study showed
      that PanNETs with favorable prognostic features have higher ERbeta expression,
      which is associated with up-regulated PR and EIG121 messenger RNA expression.
      Estrogen regulation in PanNETs could potentially help in risk stratification and
      provide a rational target for novel treatment strategies.

PMID- 25058883
TI  - Hypertriglyceridemia is a risk factor for acute kidney injury in the early phase
      of acute pancreatitis.
AB  - OBJECTIVE: The aim of this study was to investigate the risk factors for acute
      kidney injury (AKI) in patients with acute pancreatitis (AP). METHODS: Patients
      with AP were retrospectively divided into AKI group and non-AKI group. To
      investigate the risk factors for AKI, logistic regression analysis was performed
      with demography, etiologies, and comorbidities. Mortalities of patients with
      different body mass indexes were compared. RESULTS: There were 43 patients with
      AKI and 202 patients without AKI. The risk factor for AKI in AP was
      hypertriglyceridemia (odds ratio, 2.964; 95% confidence interval, 1.485-5.915; P
      = 0.007). Forty-two patients developed AKI within the first 48 hours. The
      mortalities of normal weight, overweight, and obese groups in patients with AKI
      were 16.7%, 17.4%, and 62.5%, respectively. All the 4 patients who died in the
      non-AKI group were of normal weight. CONCLUSIONS: Hypertriglyceridemia is an
      independent risk factor for AKI in the early phase of AP. Obesity does not
      increase mortality of patients without AKI. We hypothesize that the role of
      pancreatic enzymes on triglyceride accumulated in renal may be an explanation for
      AKI in the early phase of AP.

PMID- 25058882
TI  - Cholecystokinin receptor antagonist halts progression of pancreatic cancer
      precursor lesions and fibrosis in mice.
AB  - OBJECTIVES: Exogenous administration of cholecystokinin (CCK) induces hypertrophy
      and hyperplasia of the pancreas with an increase in DNA content. We hypothesized
      that endogenous CCK is involved in the malignant progression of pancreatic
      intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with
      pancreatic cancer. METHODS: The presence of CCK receptors in early PanIN lesions
      was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL
      Kras transgenic mice were randomized to receive either untreated drinking water
      or water supplemented with a CCK receptor antagonist (proglumide, 0.1 mg/mL).
      Pancreas from the mice were removed and examined histologically for number and
      grade of PanINs after 1, 2, or 4 months of antagonist therapy. RESULTS: Both CCK
      A and CCK-B receptors were identified in early stage PanINs from mouse and human
      pancreas. The grade of PanIN lesions was reversed, and progression to advanced
      lesions arrested in mice treated with proglumide compared with the controls (P =
      0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist
      treated animals compared with vehicle (P < 0.001). CONCLUSIONS: These findings
      demonstrate that endogenous CCK is in part responsible for the development and
      progression of pancreatic cancer. The use of CCK receptor antagonists may have a
      role in cancer prophylaxis in high-risk subjects and may reduce fibrosis in the
      microenvironment.

PMID- 25058884
TI  - Clinicopathological Significance of Leucine-Rich alpha2-Glycoprotein-1 in Sera of
      Patients With Pancreatic Cancer.
AB  - OBJECTIVES: Leucine-rich alpha2-glycoprotein-1 (LRG-1) is an inflammatory
      protein. Serum LRG-1 levels can reportedly be used as a cancer biomarker for
      several types of carcinoma. In the present study, we investigated the clinical
      usefulness of serum LRG-1 levels as a biomarker of pancreatic cancer. METHODS: A
      total of 124 patients with pancreatic cancer, 35 patients with chronic
      pancreatitis (CP), and 144 healthy volunteers were enrolled in the study. Serum
      LRG-1 levels were assayed by enzyme-linked immunosorbent assay.
      Immunohistochemistry was used to examine LRG-1 expression in pancreatic cancer
      tissues. RESULTS: Serum LRG-1 levels were significantly increased in patients
      with pancreatic cancer compared with CP patients and healthy volunteers. The LRG
      1 levels increased with progressive clinical stages of pancreatic cancer.
      Receiver operator curve analysis showed that a combination of carbohydrate
      antigen 19-9 and LRG-1 resulted in a higher area under the curve for the
      diagnosis of pancreatic cancer. Positive staining was observed in all cases of
      pancreatic cancer, but positive signal was scarcely detected in tissues from CP
      patients or normal surrounding tissue. CONCLUSIONS: These results suggest that
      serum LRG-1 is a promising biomarker for pancreatic cancer.

PMID- 25058885
TI  - Major and minor duodenal papillae in autoimmune pancreatitis.
AB  - OBJECTIVE: The objective of this study was to evaluate picture of the major and
      minor duodenal papillae in patients with autoimmune pancreatitis (AIP). METHODS:
      Endoscopic features of the major and minor papillae were examined in 59 and 13
      patients with AIP. After steroid therapy, changes of the major and minor papillae
      were observed in 5 and 6 patients. The major and minor papillae were observed
      with narrow band imaging in 24 and 6 patients. Biopsy specimens from the major (n
      = 50) and minor (n = 13) papillae were immunostained using an anti-IgG4 antibody.
      RESULTS: Endoscopic features of the major and minor papillae were abnormal in 26
      patients (44%; swelling [n = 20] and redness [n = 14]) and 5 patients (38%;
      swelling [n = 5]). Swelling of the pancreatic head, irregular narrowing of the
      main pancreatic duct of the pancreatic head, stenosis of the lower bile duct, and
      abundant infiltration of IgG4-positive plasma cells were more frequent in the
      patients with an abnormal major papilla compared with those with a normal major
      papilla. On narrow band imaging, dilated vessels were observed in abnormal
      papillae. After therapy, swelling of the major and minor papillae improved in all
      4 and 2 patients. CONCLUSIONS: Endoscopic features of the major and minor
      papillae were abnormal in 44% and 38% of the patients with AIP.

PMID- 25058886
TI  - Microvessel Landscape Assessment in Pancreatic Ductal Adenocarcinoma: Unclear
      Value of Targeting Endoglin (CD105) as Prognostic Factor of Clinical Outcome.
AB  - OBJECTIVES: Tumor angiogenesis based on microvessel density assessment has been
      associated with poor prognosis in several studies of patients with pancreatic
      ductal adenocarcinoma (PDAC). Expression of endoglin (CD105), a tumor-induced
      vascularization marker, has been found to represent a negative prognostic factor
      in many malignant tumors. The aim of our study was to assess the value of tumoral
      microvascularity both with pan-endothelial markers and endoglin as well, in
      correlation with the clinical outcome of patients with PDAC. METHODS: Fifty-eight
      patients with PDAC, 36 males and 22 females, with a mean (SD) age of 65.4 (10.0)
      years were included in the study. Deparaffinized sections from formalin-fixed
      areas both from the center and periphery (invasion front) of the tumors were
      immunostained for CD105 as well as for the endothelial markers CD31 and CD34.
      Tumoral angiogenesis was assessed on the basis of microvessel density (number of
      vessels per square millimeter) and on microvascular area (square micrometers) as
      well. RESULTS: High intratumoral microvascular area, in endoglin-stained
      sections, was found to be of marginal prognostic significance for recurrence (log
      rank, P 0.05). Survival was also marginally associated with CD31 intratumoral
      microvascular area (log rank, P 0.05). CONCLUSIONS: Further studies are needed
      before endoglin replaces the conventional angiogenesis markers in PDCA.

PMID- 25058887
TI  - Clinical Features and Endoscopic Treatment of Chinese Patients With Hereditary
      Pancreatitis.
AB  - OBJECTIVES: Hereditary pancreatitis (HP) has been rarely investigated in China.
      We aimed to describe clinical features and mutation frequency of Chinese patients
      with HP and to evaluate outcomes of endoscopic treatments. METHODS: Inpatients
      diagnosed with HP from January 1995 to March 2013 were included. Demographic and
      clinical data including first onset age, age at diagnosis, sex, main symptoms,
      radiological findings, and outcomes of endoscopic treatments were collected.
      Mutations in serine protease inhibitor Kazal type 1 (SPINK1), PRSS1, and cystic
      fibrosis transmembrane conductance regulator (CFTR) were analyzed. RESULTS: A
      total of 22 inpatients with HP (male, 12; female, 10) participated in this study.
      Mean (SD) age at first onset and at diagnosis were 24.5 (11.9) years and 29.1
      (11.2) years, respectively. The predominant radiological feature was pancreatic
      calcifications. Thirty-nine endoscopic retrograde cholangiopancreatography
      procedures were successfully performed on 19 cases. In the final long-term follow
      up, 21 patients got complete or incomplete remission after endoscopic retrograde
      cholangiopancreatography and/or surgery. Genetic analyses were available in 20
      patients, and mutation rates of R122H, N29I, and A16V in PRSS1 were 60%, 25% and
      5%, respectively. CONCLUSIONS: As compared with previous studies, our patient
      cohort, with a relatively higher frequency of R122H mutation, showed a much lower
      surgery rate, and endoscopic interventions may be recommended to be the first
      line treatment.

PMID- 25058888
TI  - Frequency and characterization of benign lesions in patients undergoing surgery
      for the suspicion of solid pancreatic neoplasm.
AB  - OBJECTIVES: A diagnosis of benign lesions (BLs) is reported in 5% to 21% of
      pancreatoduodenectomies performed for neoplasms; no data for body-tail resections
      are available. The aims were to investigate the frequency and characterize the
      BLs mimicking cancer in the head and the body-tail of the pancreas. METHODS: This
      study is a retrospective review of pancreatic specimenscollected from 2005 to
      2011 in the pathology database of Mainz (Germany). Patients with final diagnosis
      excluding malignancy were analyzed by histology, imaging, and clinical aspects.
      RESULTS: Among 373 patients, 33 patients (8.8%) were diagnosed with a benign
      disease: 25 (8.4%) of 298 in the pancreatic head and 8 (10.7%) of 75 in the body
      tail resections. Paraduodenal pancreatitis was diagnosed in 13 (3.5%) of 373
      patients; autoimmune pancreatitis (AIP), in 11 (2.9%); "ordinary" chronic
      pancreatitis, in 6 (1.6%); and accessory spleen, in 3 (0.8%). In pancreatic head
      resections, the most frequent diagnoses were paraduodenal pancreatitis (13/298,
      4.4%) and AIP (9/298, 3%), whereas in the body-tail, the most frequent diagnoses
      were accessory spleen (3/75, 4%), chronic pancreatitis (3/75, 4%), and AIP (2/75,
      2.7%). CONCLUSIONS: Benign lesions are observed with the same frequency
      inspecimens of the head or the body-tail of the pancreas.

PMID- 25058889
TI  - HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti-IL-6R
      Antibody in Mice.
AB  - OBJECTIVES: The limited success in achieving insulin independence of patients
      with type 1 diabetes mellitus after islet transplantation from a single donor,
      mainly due to early loss of transplanted islets, hampers clinical application of
      islet transplantation. Previously, we have shown in mice that the early loss of
      transplanted islets in the liver, the site of islet transplantation, is caused by
      innate immune rejection triggered by high-mobility group box 1 (HMGB1) protein
      released from transplanted islets. We herein determined whether the HMGB1
      mediated early loss of transplanted mouse islets is prevented by anti-interleukin
      6 receptor (IL-6R) antibody. METHODS: The effect of anti-IL-6R antibody on
      amelioration of hyperglycemia in streptozocin-induced diabetic mice receiving 200
      islets into the liver from a single donor was evaluated in association with HMGB1
      stimulated interferon-gamma production of hepatic mononuclear cells. RESULTS:
      Hyperglycemia of diabetic mice receiving 200 syngeneic islets was ameliorated
      with down-regulation of interferon-gamma production of hepatic natural killer T
      cells and neutrophils when anti-IL-6R was administered at the time of
      transplantation. This beneficial effect was also seen in allografts when
      alloimmune rejection was prevented by anti-CD4 antibody. CONCLUSIONS: These
      findings demonstrate that anti-IL-6R antibody prevented the early loss of
      intrahepatic islet grafts with inhibiting HMGB1-induced immune activation after
      islet transplantation.

PMID- 25058890
TI  - A population-based evaluation of severity and mortality among transferred
      patients with acute pancreatitis.
AB  - OBJECTIVES: This study aimed to compare severity of acute pancreatitis (AP) and
      mortality rates between transferred and nontransferred patients and to determine
      the factors that influence the decision to transfer. METHODS: A retrospective
      analysis coding a statewide administrative database in Maryland was conducted.
      Severity was defined by presence of organ failure (OF), need for intensive care
      unit (ICU), mechanical ventilation (MV), or hemodialysis. RESULTS: There were
      71,035 discharges for AP, with 1657 (2.3%) patient transfers. Transferred
      patients had more multisystem OF (5.6% vs 1.2%), need for ICU (22.8% vs 4.3%), MV
      (13.1% vs 1.4%), hemodialysis (4.2% vs 2.7%), and higher mortality (6.1% vs 1.1%)
      compared with nontransferred patients (P < 0.0001). After adjusting for disease
      severity, mortality was similar between the transferred patients and the
      nontransferred patients (OR, 1.37; 95% confidence interval, 0.96-1.97). Younger
      (OR, 0.99), African American (OR, 0.55), and uninsured (OR, 0.46) patients were
      less likely to be transferred, whereas patients with multisystem OF (OR, 3.5),
      need for ICU (OR, 2.3), or MV (OR, 2.1) were more likely to be transferred (P <
      0.0001). CONCLUSIONS: Transferred patients with AP have more severe disease and
      higher overall mortality. Mortality is similar after adjusting for disease
      severity. Disease severity, insurance status, race, and age all influence the
      decision to transfer patients with AP.

PMID- 25058891
TI  - Transcriptome analysis in cardiomyocyte-specific differentiation of murine
      embryonic stem cells reveals transcriptional regulation network.
AB  - The differentiation to cardiomyocytes is a prerequisite and an important part of
      heart development. A good understanding of the complicated cardiomyocyte
      differentiation process benefits cardiogenesis study. Embryonic stem cells
      (ESCs), cell lines with infinite ability to proliferate and to be differentiated
      into all cell types of the adult body, are important research tools for
      investigation of differentiation and meanwhile good models for developmental
      research. In the current study, genome-wide gene expression of ESCs is profiled
      through high throughput platform during cardiomyocyte-specific differentiation
      and maturation. Gene expression patterns of undifferentiated ESCs and ESC-derived
      cardiomyocytes provide a global overview of genes involved in cardiomyocyte
      specific differentiation, whereas marker gene expression profiles of both ESC
      related genes and cardiac-specific genes presented the expression pattern shift
      during differentiation in a pure ESC-derived cardiomyocyte cell culture system.
      The differentiation and maturation process was completed at day 19 after
      initiation of differentiation, according to our gene expression profile results.
      Functional analysis of regulated genes reveals over-represented biological
      processes, molecular functions and pathways during the differentiation and
      maturation process. Finally, transcription factor regulation networks were
      engineered based on gene expression data. Within these networks, the number of
      identified important regulators (Trim28, E2f4, Foxm1, Myc, Hdac1, Rara, Mef2c,
      Nkx2-5, Gata4) and possible key co-regulation modules (Nkx2-5 - Gata4 - Tbx5, Myc
      - E2F4) could be expanded. We demonstrate that a more comprehensive picture of
      cardiomyocyte differentiation and its regulation can be achieved solely by
      studying gene expression patterns. The results from our study contribute to a
      better and more accurate understanding of the regulation mechanisms during
      cardiomyocyte differentiation. 

PMID- 25058892
TI  - Performance and storage integrity of dried blood spots for PCB, BFR and pesticide
      measurements.
AB  - Dried blood spots (DBSs) can provide accurate and valuable estimates of exposure
      to environmental toxicants, and the use of information derived from archived
      newborn DBSs has enormous potential to open up new research on the impacts of
      early chemical exposure on disease. Broad application of DBS for the purpose of
      quantitative exposure estimation requires robust and validated methods. This
      study investigates the suitability of DBS analyses for population studies of
      exposure to three chemical groups: polychlorinated biphenyls (PCBs), brominated
      flame retardants (BFRs), and chlorinated pesticides. It examines background
      (matrix) contamination, recovery and extraction variability, sensitivity, and
      storage stability. DBS samples prepared using 50 MUL of adult blood were analyzed
      by GC/MS, and method performance was confirmed by using certified materials and
      paired DBS-blood samples from six volunteers. Several of the target compounds and
      their degradation products have not been previously measured in DBSs. All target
      compounds were detected in DBS samples collected from the volunteers. Sample DBS
      cards showed background contamination of several compounds. When stored at room
      temperature, target compounds, excluding PBDEs, were stable for up to one month.
      When refrigerated or frozen, stability was acceptable for all compounds up to one
      year, and multiyear storage appears acceptable at colder (e.g., -80 degrees C)
      temperatures. Multicompartment models may be used to estimate or correct for
      storage losses. Considering concentrations of contaminants for adults and
      children reported in the literature, and experimental values of detection limits
      and background contamination, DBS samples are suitable for quantifying exposures
      to many PCBs, BFRs and persistent pesticides.

PMID- 25058893
TI  - Dispersion and fate of 90Sr in the Northwestern Pacific and adjacent seas: global
      fallout and the Fukushima Dai-ichi accident.
AB  - The 3D compartment model POSEIDON-R was applied to the Northwestern Pacific and
      adjacent seas to simulate the transport and fate of (90)Sr in the period 1945
      2010 and to perform a radiological assessment on the releases of (90)Sr due to
      the Fukushima Dai-ichi nuclear accident for the period 2011-2040. The
      contamination due to runoff of (90)Sr from terrestrial surfaces was taken into
      account using a generic predictive model. A dynamical food-chain model describes
      the transfer of (90)Sr to phytoplankton, zooplankton, molluscs, crustaceans,
      piscivorous and non-piscivorous fishes. Results of the simulations were compared
      with observation data on (90)Sr for the period 1955-2010 and the budget of (90)Sr
      activity was estimated. It was found that in the East China Sea and Yellow Sea
      the riverine influx was 1.5% of the ocean influx and it was important only
      locally. Calculated concentrations of (90)Sr in water, bottom sediment and marine
      organisms before and after the Fukushima Dai-ichi accident are in good agreement
      with available experimental measurements. The concentration of (90)Sr in seawater
      would return to the background levels within one year after leakages were
      stopped. The model predicts that the concentration of (90)Sr in fish after the
      Fukushima Dai-ichi accident shall return to the background concentrations only 2
      years later due to the delay of the transfer throughout the food web and specific
      accumulation of (90)Sr. The contribution of (90)Sr to the maximal dose rate due
      to the FDNPP accident was three orders of magnitude less than that due to
      (137)Cs, and thus well below the maximum effective dose limits for the public.

PMID- 25058894
TI  - Factorization of air pollutant emissions: projections versus observed trends in
      Europe.
AB  - This paper revisits the emission scenarios of the European Commission's 2005
      Thematic Strategy on Air Pollution (TSAP) in light of today's knowledge. We
      review assumptions made in the past on the main drivers of emission changes,
      i.e., demographic trends, economic growth, changes in the energy intensity of
      GDP, fuel-switching, and application of dedicated emission control measures. Our
      analysis shows that for most of these drivers, actual trends have not matched
      initial expectations. Observed ammonia and sulfur emissions in European Union in
      2010 were 10% to 20% lower than projected, while emissions of nitrogen oxides and
      particulate matter exceeded estimates by 8% to 15%. In general, a higher
      efficiency of dedicated emission controls compensated for a lower-than-expected
      decline in total energy consumption as well as a delay in the phase-out of coal.
      For 2020, updated projections anticipate lower sulfur and nitrogen oxide
      emissions than those under the 2005 baseline, whereby the degree to which these
      emissions are lower depends on what assumptions are made for emission controls
      and new vehicle standards. Projected levels of particulates are about 10% higher,
      while smaller differences emerge for other pollutants. New emission projections
      suggest that environmental targets established by the TSAP for the protection of
      human health, eutrophication and forest acidification will not be met without
      additional measures. 

PMID- 25058895
TI  - Fish eyes and brain as primary targets for mercury accumulation - a new insight
      on environmental risk assessment.
AB  - Fish eyes and brain are highly susceptible to environmental Hg exposure but this
      issue is still scarcely investigated, mainly regarding methylmercury (MeHg)
      accumulation. Yet, Hg levels in fish lens have not been previously examined under
      field conditions. Total Hg (tHg), MeHg and inorganic Hg (iHg) levels were
      assessed in the brain, eye wall and lens of the golden grey mullet (Liza aurata)
      from an Hg contaminated area, both in winter and summer, together with water and
      sediment levels. Sampling was performed at Aveiro lagoon (Portugal) where a
      confined area (LAR) is severely contaminated by Hg. Fish brain, eye wall and lens
      accumulated higher levels of tHg, MeHg and iHg at LAR than the reference site,
      reflecting faithfully environmental spatial differences. The brain and eye wall
      responded also to the winter-summer changes found in water and sediment,
      accumulating higher levels of MeHg (and tHg) in winter. Contrarily, lens was
      unable to reflect seasonal changes, probably due to its composition and
      structural stability over time. The three neurosensory structures accumulated
      preferentially MeHg than iHg (MeHg was higher than 77% of tHg). Lens exhibited a
      higher retention capacity of MeHg (mean around 1 MUg g(-1) at LAR), accumulating
      higher levels than the other two tissues. Interestingly, MeHg and iHg levels were
      significantly correlated for the brain and eye wall but poorly associated within
      the two analysed eye components. The high levels of MeHg found in the brain, eye
      wall and lens could compromise their functions and this needs further research.

PMID- 25058896
TI  - Latex paint as a delivery vehicle for diethylphthalate and di-n-butylphthalate:
      predictable boundary layer concentrations and emission rates.
AB  - The description of emission processes of volatile and semi-volatile organic
      compounds (VOCs and SVOCs) from building products requires a detailed
      understanding of the material and the air flow conditions at the surface
      boundary. The mass flux between the surface of the material and air depends on
      the mass transfer coefficient (hm) through the boundary layer, the gas phase
      concentration of the target compound immediately adjacent to the material (y0),
      and the gas-phase concentration in bulk air (y(t)). In the present study emission
      experiments were performed in two chambers of quite different sizes (0.25 m(3)
      and 55 m(3)), and, in the larger chamber, at two different temperatures (23
      degrees C and 30 degrees C). The emitting material was latex wall paint that had
      been doped with two plasticizers, diethylphthalate (DEP) and di-n-butylphthalate
      (DnBP). The phthalate content in the paint was varied in the small chamber
      experiment to evaluate the impact of the initial concentration in the bulk
      material (C0) on the emission rate. Boundary layer theory was applied to
      calculate hm for the specific phthalates from the Sherwood number (Sh) and the
      diffusion coefficient (Dair). Then y0 was determined based on the bulk gas-phase
      concentration at steady state (y-). For both, DEP and DnBP, the y0 obtained was
      lower than the respective saturation vapor pressure (Ps). Furthermore, for both
      phthalates in latex paint, the material/air partition coefficient (C0/y0) was
      close in value to the octanol/air partition coefficient (KOA). This study
      provides a basis for designing phthalate emitting reference materials that mimic
      the emission behavior of common building materials.

PMID- 25058897
TI  - Impact of compost process temperature on organic micro-pollutant degradation.
AB  - Aerobic composting has gained considerable attention because of its ability to
      remove organic micro-pollutants. Compost process temperature is a key parameter
      controlling degradation rate. Impact of process temperature on removal of 15 key
      organic micro-pollutants often found in sewage sludge (including two metabolites)
      during sewage sludge composting was investigated at 18-70 degrees C over 52 days.
      Removal rates generally depended strongly on temperature and for all compounds an
      optimal temperature for removal was observed. Optimal temperatures for the 13
      parent compounds ranged from 25 to 70 degrees C and relative removal of the 13
      parent compounds was as high as 99% across all combinations of compound and
      temperature with an average removal of 66%. The two metabolites were both formed
      and removed during the course of composting and the data indicated that
      metabolites may very well have other optimal removal temperatures than their
      parent compounds.

PMID- 25058899
TI  - Automated fetal brain segmentation from 2D MRI slices for motion correction.
AB  - Motion correction is a key element for imaging the fetal brain in-utero using
      Magnetic Resonance Imaging (MRI). Maternal breathing can introduce motion, but a
      larger effect is frequently due to fetal movement within the womb. Consequently,
      imaging is frequently performed slice-by-slice using single shot techniques,
      which are then combined into volumetric images using slice-to-volume
      reconstruction methods (SVR). For successful SVR, a key preprocessing step is to
      isolate fetal brain tissues from maternal anatomy before correcting for the
      motion of the fetal head. This has hitherto been a manual or semi-automatic
      procedure. We propose an automatic method to localize and segment the brain of
      the fetus when the image data is acquired as stacks of 2D slices with anatomy
      misaligned due to fetal motion. We combine this segmentation process with a
      robust motion correction method, enabling the segmentation to be refined as the
      reconstruction proceeds. The fetal brain localization process uses Maximally
      Stable Extremal Regions (MSER), which are classified using a Bag-of-Words model
      with Scale-Invariant Feature Transform (SIFT) features. The segmentation process
      is a patch-based propagation of the MSER regions selected during detection,
      combined with a Conditional Random Field (CRF). The gestational age (GA) is used
      to incorporate prior knowledge about the size and volume of the fetal brain into
      the detection and segmentation process. The method was tested in a ten-fold cross
      validation experiment on 66 datasets of healthy fetuses whose GA ranged from 22
      to 39 weeks. In 85% of the tested cases, our proposed method produced a motion
      corrected volume of a relevant quality for clinical diagnosis, thus removing the
      need for manually delineating the contours of the brain before motion correction.
      Our method automatically generated as a side-product a segmentation of the
      reconstructed fetal brain with a mean Dice score of 93%, which can be used for
      further processing.

PMID- 25058900
TI  - Neurodevelopmental and behavioral effects of nonylphenol exposure during
      gestational and breastfeeding period on F1 rats.
AB  - Nonylphenols (NP) are endocrine-disruptors known to be widely present in our
      environment. This study evaluated the effects of 4-n-NP on neurobehavioral
      development and memory capacity after perinatal exposure on the offspring rats.
      Dams were gavaged with 4-n-NP (0, 50 and 200mg/kg/day) from gestational day 5 to
      postnatal day (PND) 21. Dams exposed to the higher dose lost weight during
      gestation and had a longer gestational duration. Juvenile female pups of the
      200mg 4-n-NP/kg/day group were lighter. Their thyroid somatic index (TSI) was
      also affected. For male pups, a decrease of TSI at weaning for the 200mg 4-n
      NP/kg/day group and an increase of GSI for the 50mg 4-n-NP/kg/day group were
      observed. Physical maturation (incisives and eyes) were likewise affected. In
      open field (OF) tests, females were more active than males. In the first OF (PND
      36), a treatment effect was observed only for males, particularly for the high
      dose group, which became as active as females. The second OF (PND 71) showed few
      differences between groups (treated vs control), the gender difference whatever
      the dose was not abolished. In the Morris Water Maze test, the study of the first
      30s showed that females (200mg/kg/day) were mainly affected. Their performances
      were improved by 4-n-NP. These effects were particularly important for the first
      short-term memory test and observed to a lesser extent in the second evaluation
      of the long-term memory (PND 69). These data showed that perinatal 4-n-NP
      exposure induced behavioral and neuro-developmental impairments from 50mg/kg/day.

PMID- 25058901
TI  - Effects of low-level sarin and cyclosarin exposure on hippocampal subfields in
      Gulf War Veterans.
AB  - BACKGROUND: More than 100,000 US troops were potentially exposed to chemical
      warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at
      Khamisiyah, Iraq was destroyed during the 1991 Gulf War (GW). We previously
      reported reduced hippocampal volume in GW veterans with suspected GB/GF exposure
      relative to matched, unexposed GW veterans estimated from 1.5T magnetic resonance
      images (MRI). Here we investigate, in a different cohort of GW veterans, whether
      low-level GB/GF exposure is associated with structural alterations in specific
      hippocampal subfields, estimated from 4T MRI. METHODS: The Automatic Segmentation
      of Hippocampal Subfields (ASHS) technique was used to quantify CA1, CA2, CA3 and
      dentate gyrus (DG), and subiculum (SUB) subfields volumes from high-resolution T2
      weighted images acquired on a 4T MR scanner in 56 GW veterans with suspected
      GB/GF exposure and 56 "matched" unexposed GW veterans (mean age 49+/-7 years).
      RESULTS: GB/GF exposed veterans had smaller CA2 (p=0.003) and CA3/DG (p=0.01)
      subfield volumes compared to matched, unexposed GW veterans. There were no group
      difference in total hippocampal volume, quantified with FreeSurfer, and no dose
      response relationship between estimated levels of GB/GF exposure and total
      hippocampal or subfield volume. CONCLUSIONS: These findings extend our previous
      report of structural alterations in the hippocampi of GW veterans with suspected
      GB/GF exposure to volume changes in the CA2, CA3, and DG hippocampal subfields in
      a different cohort of GW veterans with suspected GB/GF exposure.

PMID- 25058902
TI  - Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral device
      compared to keratoplasty for the treatment of corneal ectasia.
AB  - PURPOSE: To compare the ocular characteristics and visual outcomes of eyes with
      corneal ectasia that were fitted with the Prosthetic Replacement of the Ocular
      Surface Ecosystem (PROSE) scleral device to those that underwent keratoplasty.
      DESIGN: Retrospective, comparative case series. METHODS: We reviewed the charts
      of consecutive patients with corneal ectasia that were evaluated for PROSE or
      underwent keratoplasty at our institution. Clinical data, topographic indices,
      and corneal thickness were reviewed, and eyes were stratified according to the
      Amsler-Krumeich classification for severity of ectasia. Only the more severe eye
      of each patient was included in the study. We compared visual acuity before and
      after PROSE fitting or keratoplasty. For PROSE evaluations, achievement of
      satisfactory fit and continued wear at 1 year of follow-up were recorded.
      RESULTS: From 2010 to 2012, 36 patients underwent PROSE evaluation for corneal
      ectasia while 37 patients underwent keratoplasty for the same indication. All
      eyes were successfully fitted with the PROSE device. Eyes in the keratoplasty
      group had more severe ectasia than eyes in the PROSE group (P = .038). Visual
      acuity was achieved more rapidly in the PROSE cohort compared to keratoplasty,
      and mean visual acuity was significantly better for all eyes (P < .0001) and when
      including only eyes with stage 4 ectasia (P < .001). More eyes with stage 4
      ectasia achieved 20/25 visual acuity after PROSE than after keratoplasty (P =
      .003). At 1 year follow-up in the PROSE cohort, Snellen acuity was 20/28 (P =
      .108 vs keratoplasty), improving to 20/25 with over-refraction (P = .006 vs
      keratoplasty). CONCLUSIONS: Eyes with advanced corneal ectasia can be
      successfully fitted with the PROSE device, and the visual acuity outcome for
      stage 4 ectasia was better and more rapid compared to keratoplasty. The acuity
      remained excellent with 1 year of follow-up. PROSE evaluation should be
      considered in patients with advanced corneal ectasia before proceeding to
      keratoplasty, especially if the ectasia is deemed stable.

PMID- 25058903
TI  - The analgesic effect of dipyrone in peripheral tissue involves two different
      mechanisms: neuronal K(ATP) channel opening and CB(1) receptor activation.
AB  - Dipyrone (metamizole) is an analgesic pro-drug used to control moderate pain. It
      is metabolized in two major bioactive metabolites: 4-methylaminoantipyrine (4
      MAA) and 4-aminoantipyrine (4-AA). The aim of this study was to investigate the
      participation of peripheral CB1 and CB2 cannabinoid receptors activation in the
      anti-hyperalgesic effect of dipyrone, 4-MAA or 4-AA. PGE2 (100ng/50uL/paw) was
      locally administered in the hindpaw of male Wistar rats, and the mechanical
      nociceptive threshold was quantified by electronic von Frey test, before and 3h
      after its injection. Dipyrone, 4-MAA or 4-AA was administered 30min before the
      von Frey test. The selective CB1 receptor antagonist AM251, CB2 receptor
      antagonist AM630, cGMP inhibitor ODQ or KATP channel blocker glibenclamide were
      administered 30min before dipyrone, 4-MAA or 4-AA. The antisense-ODN against CB1
      receptor expression was intrathecally administered once a day during four
      consecutive days. PGE2-induced mechanical hyperalgesia was inhibited by dipyrone,
      4-MAA, and 4-AA in a dose-response manner. AM251 or ODN anti-sense against
      neuronal CB1 receptor, but not AM630, reversed the anti-hyperalgesic effect
      mediated by 4-AA, but not by dipyrone or 4-MAA. On the other hand, the anti
      hyperalgesic effect of dipyrone or 4-MAA was reversed by glibenclamide or ODQ.
      These results suggest that the activation of neuronal CB1, but not CB2 receptor,
      in peripheral tissue is involved in the anti-hyperalgesic effect of 4
      aminoantipyrine. In addition, 4-methylaminoantipyrine mediates the anti
      hyperalgesic effect by cGMP activation and KATP opening. 

PMID- 25058904
TI  - The effect of dinitrosyl iron complexes with glutathione and S-nitrosoglutathione
      on the development of experimental endometriosis in rats: a comparative studies.
AB  - It has been established that intraperitoneal bolus administration of S
      nitrosoglutathione (GS-NO) (12.5MUmoles/kg; 10 injections in 10 days), beginning
      with day 4 after transplantation of two 2-mm autologous fragments of endometrial
      tissue onto the inner surface of the abdominal wall of rats with surgically
      induced (experimenta) endometriosis failed to prevent further growth of
      endometrioid (EMT) and additive tumors, while treatment of animals with
      dinitrosyl iron complexes (DNIC) with glutathione (12.5MUmoles/kg, 10 injections
      in 10 days) suppressed tumor growth virtually completely. The histological
      analysis of EMT samples of GS-NO-treated rats revealed pathological changes
      characteristic of control (non-treated with GS-NO or DNIC) rats with experimental
      endometriosis. EPR studies established the presence of the active form of
      ribonucleotide reductase, a specific marker for rapidly proliferating tumors, in
      EMT samples of both control and GS-NO-treated animals. Noteworthy, in small-size
      EMT and adjacent tissues of DNIC-treated rats the active form of ribonucleotide
      reductase and pathological changes were not found. 

PMID- 25058906
TI  - The role of Bcl-2 family proteins in pulmonary fibrosis.
AB  - Pulmonary fibrosis is characterized by epithelial injury, abnormal tissue repair,
      fibroproliferation and loss of pulmonary function as a result of a complex
      interaction of multiple cellular and molecular processes. There is accumulating
      evidence in support of a role for apoptosis in the pathogenesis of interstitial
      lung diseases. The Bcl-2 (B-cell lymphoma-2) family of proteins, which consists
      of antiapoptotic and pro-apoptotic members, is a critical regulator for apoptosis
      and development of pulmonary fibrosis. The association between Bcl-2 family
      members and various pathways and mediators has been also described in the
      pulmonary fibrosis. This article reviews the recent advances regarding the roles
      of Bcl-2 family as the apoptosis-regulatory factors in pulmonary fibrosis from
      human tissue studies, animal models, ex vivo and in vitro studies. Further
      understanding of apoptosis signaling regulation through Bcl-2 family proteins in
      the lung tissue may lead to better design of new therapeutic interventions for
      pulmonary fibrosis. 

PMID- 25058907
TI  - Atrial natriuretic peptide (ANP) inhibits DMBA/croton oil induced skin tumor
      growth by modulating NF-kappaB, MMPs, and infiltrating mast cells in swiss albino
      mice.
AB  - Cardiac hormone atrial natriuretic peptide (ANP) and its receptor, natriuretic
      peptide receptor-A (NPR-A) are implicated as a vital regulator of cancer cell
      growth and tumor progression. However, the underlying mechanism by which ANP
      opposes the cancer growth in in-vivo remains unknown. Herein, we investigated the
      anti-cancer activity of ANP on 7, 12-dimethyl benzanthracence (DMBA)/Croton oil-
      induced two-step skin carcinogenic mouse model. Skin tumor incidence and tumor
      volume were recorded during the experimental period of 16 weeks. ANP (1 MUg/kg
      body weight/alternate days for 4 weeks) was injected subcutaneously from the 13th
      week of DMBA/Croton oil induction. ANP treatment markedly inhibited the skin
      tumor growth (P<0.001). A significant reduction in the level of NF-kappaB
      activation (P<0.001), infiltrating mast cell count (P<0.01) and MMP-2/-9
      (P<0.001, respectively) were noticed in the ANP treated mice skin tissue.
      Further, ANP treatment revert back the altered levels of serum LDH-4, C-reactive
      protein (CRP), and enzymatic antioxidants (SOD and CAT activities) to near normal
      level. Taken together, the results of this study suggest that ANP opposes the
      skin carcinogenesis by suppressing the inflammatory response and MMPs.

PMID- 25058905
TI  - Cisplatin in cancer therapy: molecular mechanisms of action.
AB  - Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known
      chemotherapeutic drug. It has been used for treatment of numerous human cancers
      including bladder, head and neck, lung, ovarian, and testicular cancers. It is
      effective against various types of cancers, including carcinomas, germ cell
      tumors, lymphomas, and sarcomas. Its mode of action has been linked to its
      ability to crosslink with the purine bases on the DNA; interfering with DNA
      repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in
      cancer cells. However, because of drug resistance and numerous undesirable side
      effects such as severe kidney problems, allergic reactions, decrease immunity to
      infections, gastrointestinal disorders, hemorrhage, and hearing loss especially
      in younger patients, other platinum-containing anti-cancer drugs such as
      carboplatin, oxaliplatin and others, have also been used. Furthermore,
      combination therapies of cisplatin with other drugs have been highly considered
      to overcome drug-resistance and reduce toxicity. This comprehensive review
      highlights the physicochemical properties of cisplatin and related platinum-based
      drugs, and discusses its uses (either alone or in combination with other drugs)
      for the treatment of various human cancers. A special attention is paid to its
      molecular mechanisms of action, and its undesirable side effects. 

PMID- 25058908
TI  - Etamicastat, a new dopamine-beta-hydroxylase inhibitor, pharmacodynamics and
      metabolism in rat.
AB  - Despite the importance of sympathetic nervous system in pathophysiological
      mechanisms of cardiac heart failure and essential hypertension, therapy
      specifically targeting the sympathetic nervous system is currently underutilized.
      Etamicastat is a novel dopamine-beta-hydroxylase (DBH) inhibitor that is oxidized
      into BIA 5-965 and deaminated followed by oxidation to BIA 5-998, which
      represents 13% of total etamicastat and quantified metabolites. However, the
      primary metabolic pathway of etamicastat in rats was found to be the N
      acetylation (BIA 5-961), which represents 44% of total etamicastat and quantified
      metabolites. Trace amounts of BIA 5-961 de-sulfated and S-glucuronide were also
      detected. All the main metabolites of etamicastat inhibited DBH with IC50 values
      of 306 (228, 409), 629 (534, 741), 427 (350, 522) nM for BIA 5-965, BIA 5-998 and
      BIA 5-961, respectively. However, only etamicastat (IC50 of 107 (94; 121) nM) was
      able to reduce catecholamine levels in sympathetic nervous system innervated
      peripheral tissues, without effect upon brain catecholamines. Quantitative whole
      body autoradiography revealed a limited transfer of etamicastat related
      radioactivity to brain tissues and the mean recovery of radioactivity was ~90% of
      the administered radioactive dose, eliminated primarily via renal excretion over
      5 days. The absolute oral bioavailability of etamicastat was 64% of the
      administered dose. In conclusion, etamicastat is a peripheral selective DBH
      inhibitor mainly N-acetylated in the aminoethyl moiety and excreted in urine.
      Etamicastat main metabolites inhibit DBH, but only etamicastat demonstrated
      unequivocal pharmacological effects as a DBH inhibitor with impact upon the
      activity of the sympathetic nervous system under in vivo conditions.

PMID- 25058909
TI  - The role of TRPM8 in the Guinea-pig bladder-cooling reflex investigated using a
      novel TRPM8 antagonist.
AB  - Patients with overactive bladder often exhibit abnormal bladder contractions in
      response to intravesical cold saline (positive ice-water test). The molecular
      entity involved in cold sensation within the urinary bladder is unknown, but a
      potential candidate is the ion channel, transient receptor potential (melastatin)
      8 (TRPM8). The objective of the present study was to investigate the role of
      TRPM8 in a bladder-cooling reflex evoked in anaesthetised guinea-pigs that is
      comparable to the positive ice-water test seen in patients. Guinea-pig TRPM8 was
      cloned from L6 dorsal root ganglia (DRG) and expressed in HEK293 cells.
      Functional agonist- and cold-induced Ca2+ influx and electrophysiology assays
      were performed in these cells, and for comparison in HEK293 cells expressing
      human TRPM8, using a novel TRPM8 antagonist, the S-enantiomer of 1-phenylethyl 4
      (benzyloxy)-3-methoxybenzyl (2-aminoethyl) carbamate hydrochloride (PBMC).
      Potency data from these assays was used to calculate intravenous infusion
      protocols for targeted plasma concentrations of PBMC in studies on micturition
      reflexes evoked by intravesical infusion of menthol or cold saline in
      anaesthetised guinea-pigs. Tissue expression of TRPM8 in guinea-pig bladder,
      urethra and in dorsal root ganglia neurones traced from the bladder was also
      investigated. TRPM8 mRNA and protein were detected in L6 dorsal root ganglia,
      bladder urothelium and smooth muscle. PBMC antagonised in vitro activation of
      human and guinea-pig TRPM8 and reversed menthol and cold-induced facilitation of
      the micturition reflex at plasma concentrations consistent with in vitro
      potencies. The present data suggest that the bladder-cooling reflex in the guinea
      pig involves TRPM8. The potential significance of TRPM8 in bladder disease states
      deserves future investigation.

PMID- 25058910
TI  - A novel CXCR4-selective high-affinity fluorescent probe and its application in
      competitive binding assays.
AB  - We recently developed a new, rapid, and specific bioassay system that employs a
      fluorescent probe fabricated from our discovered CXCR4-specific ligand DV1. This
      new probe sensitively and selectively blocks the binding of native and synthetic
      ligands to CXCR4 at nanomolar levels, with a capability comparable to that seen
      with a conventional CXCR4 antibody. This nonradioactive, direct, and CXCR4
      specific high-affinity screening system provides a new platform for CXCR4
      targeted drug screening, as well as for the development of new probes for other
      GPCRs. 

PMID- 25058911
TI  - Evaluation of ventriculoperitoneal shunt in the treatment of intracranial
      hypertension in the patients with cryptococcal meningitis: a report of 12 cases.

PMID- 25058912
TI  - Oral administration of squid lecithin-transphosphatidylated phosphatidylserine
      improves memory impairment in aged rats.
AB  - Recently, lecithin-derived phosphatidylserine (PS), which originates from marine
      life, has received much attention as a viable alternative to bovine cerebral
      cortex PS. In this study, the use of squid phosphatidylcholine
      transphosphatidylated PS (SQ-PS) was evaluated through examination of its
      ameliorating effects on age-associated learning and memory deficits in rats. Aged
      rats were orally administered SQ-PS (10, 20, or 50 mg/kg per day) once a day for
      seven days 30 min prior to behavioral assessment in a Morris water maze. SQ-PS
      administration produced significant dose-dependent improvements in escape latency
      for finding the platform in the Morris water maze in the aged rats even though
      Soy-PS administration also exhibited comparable improvements with SQ-PS.
      Biochemical alterations in the hippocampal cholinergic system, including changes
      in choline acetyltransferase and acetylcholinesterase immunoreactivity, were
      consistent with the behavioral results. In addition, SQ-PS treatment
      significantly restored age-associated decreases of choline transporter and
      muscarinic acetylcholine receptor type 1 mRNA expression in the hippocampus.
      These results demonstrate that orally administered SQ-PS dose-dependently aids in
      the improvement of memory deficits that occur during normal aging in rats. This
      suggests that SQ-PS may be a useful therapeutic agent in the treatment of
      diminished memory function in elderly people.

PMID- 25058913
TI  - Local modification of the microstructure and electrical properties of
      multifunctional Au-YSZ nanocomposite thin films by laser interference patterning.
AB  - Nanocomposite films consisting of gold nanoparticles embedded in an yttria
      stabilized zirconia matrix (Au-YSZ) have been synthesized with different gold
      loadings by reactive magnetron sputtering followed by ex situ annealing in air or
      laser interference patterning (LIP) treatment. It is shown that the electrical
      conductivity of the nanocomposite films can be modified to a large extent by
      changing the gold loading, by thermal annealing, or by LIP. The structural and
      microstructural analyses evidenced the segregation of metallic gold in
      crystalline form for all synthesis conditions and treatments applied. Thermal
      annealing above 400  degrees C is observed to trigger the growth of pre-existing
      nanoparticles in the volume of the films. Moreover, pronounced segregation of
      gold to the film surface is observed for Au/(Au + Zr + Y) ratios above 0.40,
      which may prevent the use of thermal annealing to functionalize gold-rich Au-YSZ
      coatings. In contrast, significant modifications of the microstructure were
      detected within the interference spot (spot size close to 2 * 2 mm) of LIP
      treatments only for the regions corresponding to constructive interference. As a
      consequence, besides its already demonstrated ability to modify the friction
      behavior of Au-YSZ films, the LIP treatment enables local tailoring of their
      electrical resistivity. The combination of these characteristics can be of great
      interest for sliding electrical contacts. 

PMID- 25058914
TI  - New spectral-spatial imaging algorithm for full EPR spectra of multiline
      nitroxides and pH sensitive trityl radicals.
AB  - An algorithm is derived and demonstrated that reconstructs an EPR spectral
      spatial image from projections with arbitrarily selected gradients. This approach
      permits imaging wide spectra without the use of the very large sweep widths and
      gradients that would be required for spectral-spatial imaging with filtered back
      projection reconstruction. Each projection is defined as the sum of contributions
      at the set of locations in the object. At each location gradients shift the
      spectra in the magnetic field domain, which is equivalent to a phase change in
      the Fourier-conjugate frequency domain. This permits solution of the problem in
      the frequency domain. The method was demonstrated for 2D images of phantoms
      consisting of (i) two tubes containing (14)N and (15)N nitroxide and (ii) two
      tubes containing a pH sensitive trityl radical at pH 7.0 and 7.2. In each case
      spectral slices through the image agree well with the full spectra obtained in
      the absence of gradient. 

PMID- 25058915
TI  - An evaluation of speech production in two boys with neurodevelopmental disorders
      who received communication intervention with a speech-generating device.
AB  - BACKGROUND: Children with neurodevelopmental disorders often present with little
      or no speech. Augmentative and alternative communication (AAC) aims to promote
      functional communication using non-speech modes, but it might also influence
      natural speech production. METHOD: To investigate this possibility, we provided
      AAC intervention to two boys with neurodevelopmental disorders and severe
      communication impairment. Intervention focused on teaching the boys to use a
      tablet computer-based speech-generating device (SGD) to request preferred
      stimuli. During SGD intervention, both boys began to utter relevant single words.
      In an effort to induce more speech, and investigate the relation between SGD
      availability and natural speech production, the SGD was removed during some
      requesting opportunities. RESULTS: With intervention, both participants learned
      to use the SGD to request preferred stimuli. After learning to use the SGD, both
      participants began to respond more frequently with natural speech when the SGD
      was removed. CONCLUSION: The results suggest that a rehabilitation program
      involving initial SGD intervention, followed by subsequent withdrawal of the SGD,
      might increase the frequency of natural speech production in some children with
      neurodevelopmental disorders. This effect could be an example of response
      generalization.

PMID- 25058916
TI  - Correlating particle deformation with water concentration profiles during latex
      film formation: reasons that softer latex films take longer to dry.
AB  - During the past two decades, an improved understanding of the operative particle
      deformation mechanisms during latex film formation has been gained. For a
      particular colloidal dispersion, the Routh-Russel deformation maps predict the
      dominant mechanism for particle deformation under a particular set of conditions
      (evaporation rate, temperature, and initial film thickness). Although qualitative
      tests of the Routh-Russel model have been reported previously, a systematic study
      of the relationship between the film-formation conditions and the resulting water
      concentration profiles is lacking. Here, the water distributions during the film
      formation of a series of acrylic copolymer latexes with varying glass-transition
      temperatures, Tg (values of -22, -11, 4, and 19  degrees C), have been obtained
      using GARField nuclear magnetic resonance profiling. A significant reduction in
      the rate of water loss from the latex copolymer with the lowest Tg was found,
      which is explained by its relatively low polymer viscosity enabling the growth of
      a coalesced skin layer. The set of processing parameters where the drying first
      becomes impeded occurs at the boundary between the capillary deformation and the
      wet sintering regimes of the Routh-Russel model, which provides strong
      confirmation of the model's validity. An inverse correlation between the model's
      dimensionless control parameter and the dimensionless drying time is discovered,
      which is useful for the design of fast-drying waterborne films. 

PMID- 25058918
TI  - Mitochondrial dysfunction and oxidative damage in the brain of diet-induced obese
      rats but not in diet-resistant rats.
AB  - AIMS: It has been suggested that obesity triggered by consuming a high-fat diet
      (HF) can account for oxidative damage and mitochondrial dysfunction. Thus, we aim
      to explore the oxidative stress and mitochondrial dysfunction detected in the
      brain of diet-induced obese (DIO) rats. MAIN METHODS: Sprague-Dawley (SD) rats
      were fed either a HF diet or a normal-fat (NF) diet for 10weeks to obtain the
      control (CON), DIO and diet-resistant (DR) rats. d-Galactose was injected
      subcutaneously for 10weeks to establish oxidative stress model (MOD) rats. Then,
      the levels of total antioxidant capacity (T-AOC), lipid peroxidation (LPO),
      malondialdehyde (MDA), both in plasma and brain tissue, and catalase (CAT) in
      plasma were measured using enzymic assay kits and the levels of ghrelin,
      neuropeptide Y (NPY) and leptin in both plasma and brain tissue were measured by
      using enzyme-linked immunosorbent assay (ELISA) kits. Mitochondrial reactive
      oxygen species (ROS) formation in brain tissues was detected with 2, 7
      dichlorofluorescein diacetate (DCFH2-DA) dyeing. The mitochondrial membrane
      potential (MMP) was measured with tetrachloro-tetraethyl benzimidazol
      carbocyanine iodide (JC-1) by a flow cytometer. KEY FINDINGS: HF diet leads to an
      obese or DR state characterized by increased or decreased adiposity. The HF diet
      increased brain LPO, which was accompanied by lower ghrelin levels in DIO rats
      compared with DR rats. In addition, the increased mitochondrial ROS and lower MMP
      were detected in DIO rat comparing with DR rats. SIGNIFICANCE: The current
      results demonstrated that mitochondrial dysfunction and oxidative damage in the
      brains of DIO rats, induced by HF diets, might be measurable.

PMID- 25058917
TI  - Using high resolution imaging to determine trafficking of corticotropin-releasing
      factor receptors in noradrenergic neurons of the rat locus coeruleus.
AB  - Trafficking of G protein-coupled receptors (GPCRs) is a critical determinant of
      cellular sensitivity of neurons. To understand how endogenous or exogenous
      ligands impact cell surface expression of GPCRs, it is essential to employ
      approaches that achieve superior anatomical resolution at the synaptic level. In
      situations in which light and fluorescence microscopy techniques may provide only
      limited resolution, electron microscopy provides enhanced subcellular precision.
      Dual labeling immunohistochemistry employing visually distinct immunoperoxidase
      and immunogold markers has been an effective approach for elucidating complex
      receptor profiles at the synapse and to definitively establish the localization
      of individual receptors and neuromodulators to common cellular profiles. The
      immuno-electron microscopy approach offers the potential for determining membrane
      versus intracellular protein localization, as well as the association with
      various identifiable cellular organelles. Corticotropin-releasing factor (CRF) is
      an important regulator of endocrine, autonomic, immunological, behavioral and
      cognitive limbs of the stress response. Dysfunction of this neuropeptide system
      has been associated with several psychiatric disorders. This review summarizes
      findings from neuroanatomical studies, with superior spatial resolution, that
      indicate that the distribution of CRF receptors is a highly dynamic process that,
      in addition to being sexually dimorphic, involves complex regulation of receptor
      trafficking within extrasynaptic sites that have significant consequences for
      adaptations to stress, particularly within the locus coeruleus (LC), the major
      brain norepinephrine-containing nucleus. 

PMID- 25058919
TI  - Rosmarinic acid mediated neuroprotective effects against H2O2-induced neuronal
      cell damage in N2A cells.
AB  - AIMS: Oxidative stress plays a key role in several ailments including
      neurodegenerative conditions. The aim of the study was to demonstrate the effect
      of rosmarinic acid (RA) in preventing oxidative stress related death of neuronal
      cell lines. MAIN METHODS: In the present study, we demonstrated direct
      neuroprotective effect of RA using H2O2-induced oxidative challenge in N2A mouse
      neuroblastoma cells. The mechanism of neutralization of H2O2-induced toxicity by
      RA was evaluated using MTT, lactate dehydrogenase, mitochondrial membrane
      potential (MMP), intracellular ROS, and comet assays. Up-regulation of brain
      neuronal markers at molecular level was performed by RT-PCR. KEY FINDINGS:
      Results presented in the paper indicate that H2O2-induced cytotoxicity in N2A
      cells was suppressed by treatment with RA. Moreover, RA is very effective in
      attenuating the disruption of lactate dehydrogenase, mitochondrial membrane
      potential and intracellular ROS. Pretreatment with RA significantly prevents
      genotoxicity (3.7-fold, p<0.01) and promotes the up-regulation of tyrosine
      hydroxylase (TH) (4.5-fold, p<0.01), and brain-derived neurotrophic factor (BDNF)
      genes (5.4-fold, p<0.01) against H2O2-induced cytotoxicity in N2A cells.
      SIGNIFICANCE: Our results revealed that N2A cells are suitable cellular models to
      evaluate neuroprotective effects of RA, and suggest that RA may potentially serve
      as an agent for prevention of several human neurodegenerative diseases caused by
      oxidative stress.

PMID- 25058920
TI  - Hydrogen peroxide inhibits proliferation and endothelial differentiation of bone
      marrow stem cells partially via reactive oxygen species generation.
AB  - AIMS: The present study was to investigate the effect of hydrogen peroxide (H2O2)
      on bone marrow stem cells and their endothelial differentiation and the
      underlying mechanisms in vitro. MAIN METHODS: Rat bone marrow multipotent adult
      progenitor cells (MAPCs) were used as the source of bone marrow stem cells, and
      treated with H2O2 (with the final concentration from 0 to 50 MUM) with or without
      N-acetylcysteine (NAC, 0.1 mM). Reactive oxygen species (ROS) was measured by
      electron paramagnetic resonance (EPR) and fluorescent microscope. Flow cytometry
      and immunoblotting were used to determine apoptosis and differentiation of MAPCs.
      KEY FINDINGS: H2O2 generated a significant amount of intracellular and
      extracellular ROS in the culture system, substantially inhibited the
      proliferation of MAPCs and Oct-4 expression, and induced their apoptosis in a
      dose-dependent manner. Exposure to H2O2 also significantly attenuated the
      endothelial differentiation of MAPCs with reduced expression of endothelial
      markers CD31 and FLK-1 as well as impaired in vitro vascular structure formation.
      Both intracellular and extracellular ROS production from H2O2 were blocked by
      NAC. NAC treatment effectively prevented H2O2-induced reduction of Oct-4
      expression in the cells. However, NAC treatment only partially prevented H2O2
      induced apoptosis, and inhibition of cell proliferation and endothelial
      differentiation of MAPCs. SIGNIFICANCE: H2O2 exposure suppressed Oct-4 expression
      in MAPCs through ROS-dependent mechanism, while increasing the apoptosis of MAPCs
      and inhibiting their proliferation and endothelial differentiation with a
      mechanism partially due to ROS generation in vitro.

PMID- 25058921
TI  - Dietary heat-killed Lactobacillus brevis SBC8803 promotes voluntary wheel-running
      and affects sleep rhythms in mice.
AB  - AIMS: We previously reported that heat-killed Lactobacillus brevis SBC8803
      enhances appetite via changes in autonomic neurotransmission. Here we assessed
      whether a diet supplemented with heat-killed SBC8803 affects circadian locomotor
      rhythmicity and sleep architecture. MAIN METHODS AND KEY FINDINGS: Daily total
      activity gradually increased in mice over 4 weeks and supplementation with heat
      killed SBC8803 significantly intensified the increase, which reached saturation
      at 25 days. Electroencephalography revealed that SBC8803 supplementation
      significantly reduced the total amount of time spent in non-rapid eye movement
      (NREM) sleep and increased the amount of time spent being awake during the latter
      half of the nighttime, but tended to increase the total amount of time spent in
      NREM sleep during the daytime. Dietary supplementation with SBC8803 can extend
      the duration of activity during the nighttime and of sleep during the daytime.
      Daily voluntary wheel-running and sleep rhythmicity become intensified when heat
      killed SBC8803 is added to the diet. SIGNIFICANCE: Dietary heat-killed SBC8803
      can modulate circadian locomotion and sleep rhythms, which might benefit
      individuals with circadian rhythms that have been disrupted by stress or ageing.

PMID- 25058922
TI  - CKD712, a synthetic isoquinoline alkaloid, enhances the anti-cancer effects of
      paclitaxel in MDA-MB-231 cells through regulation of PTEN.
AB  - AIMS: It has been reported that in human glioblastoma cells, phosphotase and
      tensin homolog (PTEN) positive cells are more prone to paclitaxel-induced
      apoptosis than PTEN-negative cells. We investigated whether (S)-1-(alpha
      naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD712) enhances
      the therapeutic effects of paclitaxel (including effects on cellular
      proliferation, invasion and apoptosis) in MDA-MB-231 cells through PTEN and NF
      kappaB activity. MAIN METHODS: Cellular proliferation, invasion and apoptosis
      were assessed by MTT, Western blot analysis, and TUNEL assay. KEY FINDINGS: The
      combination of paclitaxel and CKD712 significantly decreased cell growth,
      invasion and MMP-9 expression/activity compared with paclitaxel alone. CKD712
      enhanced the inhibition of cell growth and invasion in response to paclitaxel in
      scramble siRNA-transfected, but not siPTEN-transfected cells. CKD712
      significantly increased the levels of apoptosis induced by paclitaxel and this
      apoptosis was accompanied by reduced expression of Bcl-xL but increased
      activation of caspase-3. TUNEL assay further confirms that CKD712 enhanced the
      apoptotic effect of paclitaxel. Interestingly, over-expression of PTEN decreased
      phosphorylation of IkappaBalpha and NF-kappaB expression in the nucleus,
      indicating that PTEN modifies NF-kappaB activity in MDA-MB-231 cells. CKD712
      treatment also significantly reduced expression of p-IkappaB and NF-kappaB
      activity in TNF-alpha activated cells. SIGNIFICANCE: CKD712 strongly enhances the
      anti-cancer effects (proliferation, invasion, and apoptosis) of paclitaxel on MDA
      MB-231 cells by regulating PTEN and NF-kappaB activity.

PMID- 25058923
TI  - H-Man: a planar, H-shape cabled differential robotic manipulandum for experiments
      on human motor control.
AB  - In the last decades more robotic manipulanda have been employed to investigate
      the effect of haptic environments on motor learning and rehabilitation. However,
      implementing complex haptic renderings can be challenging from technological and
      control perspectives. We propose a novel robot (H-Man) characterized by a
      mechanical design based on cabled differential transmission providing advantages
      over current robotic technology. The H-Man transmission translates to extremely
      simplified kinematics and homogenous dynamic properties, offering the possibility
      to generate haptic channels by passively blocking the mechanics, and eliminating
      stability concerns. We report results of experiments characterizing the
      performance of the device (haptic bandwidth, Z-width, and perceived impedance).
      We also present the results of a study investigating the influence of haptic
      channel compliance on motor learning in healthy individuals, which highlights the
      effects of channel compliance in enhancing proprioceptive information. The
      generation of haptic channels to study motor redundancy is not easy for actual
      robots because of the needs of powerful actuation and complex real-time control
      implementation. The mechanical design of H-Man affords the possibility to
      promptly create haptic channels by mechanical stoppers (on one of the motors)
      without compromising the superior backdriveability and high isotropic
      manipulability. This paper presents a novel robotic device for motor control
      studies and robotic rehabilitation. The hardware was designed with specific
      emphasis on the mechanics that result in a system that is easy to control,
      homogeneous, and is intrinsically safe for use. 

PMID- 25058925
TI  - Ribosome display enhanced by next generation sequencing: a tool to identify
      antibody-specific peptide ligands.
AB  - Detection of antibodies in serum has many important applications. Our goal was to
      develop a facile general experimental approach for identifying antibody-specific
      peptide ligands that could be used as the reagents for antibody detection. Our
      emphasis was on an approach that would allow identification of peptide ligands
      for antibodies in serum without the need to isolate the target antibody or to
      know the identity of its antigen. We combined ribosome display (RD) with the
      analysis of peptide libraries by next generation sequencing (NGS) of their coding
      RNA to facilitate identification of antibody-specific peptide ligands from random
      sequence peptide library. We first demonstrated, using purified antibodies, that
      with our approach-specific peptide ligands for antibodies with simple linear
      epitopes, as well as peptide mimotopes for antibodies recognizing complex
      epitopes, were readily identified. Inclusion of NGS analysis reduced the number
      of RD selection rounds that were required to identify specific ligands and
      facilitated discrimination between specific and spurious nonspecific sequences.
      We then used a model of human serum spiked with a known target antibody to
      develop NGS-based analysis that allowed identification of specific ligands for a
      target antibody in the context of an overwhelming amount of unrelated
      immunoglobins present in serum. 

PMID- 25058927
TI  - Spectrophotometric determination and removal of unchelated europium ions from
      solutions containing Eu-diethylenetriaminepentaacetic acid chelate-peptide
      conjugates.
AB  - Europium chelates conjugated with peptide ligands are routinely used as probes
      for conducting in vitro binding experiments. The presence of unchelated Eu ions
      in these formulations gives high background luminescence and can lead to poor
      results in binding assays. In our experience, the reported methods for
      purification of these probes do not achieve adequate removal of unchelated metal
      ions in a reliable manner. In this work, a xylenol orange-based assay for the
      quantification of unchelated metal ions was streamlined and used to determine
      levels of metal ion contamination as well as the success of metal ion removal on
      attempted purification. We compared the use of Empore chelating disks and Chelex
      100 resin for the selective removal of unchelated Eu ions from several Eu
      diethylenetriaminepentaacetic acid chelate-peptide conjugates. Both purification
      methods gave complete and selective removal of the contaminant metal ions.
      However, Empore chelating disks were found to give much higher recoveries of the
      probes under the conditions used. Related to the issue of probe recovery, we also
      describe a significantly more efficient method for the synthesis of one such
      probe using Rink amide AM resin in place of Tentagel S resin. 

PMID- 25058926
TI  - A fluorescent carbapenem for structure function studies of penicillin-binding
      proteins, beta-lactamases, and beta-lactam sensors.
AB  - By reacting fluorescein isothiocyanate with meropenem, we have prepared a
      carbapenem-based fluorescent beta-lactam. Fluorescein-meropenem binds both
      penicillin-binding proteins and beta-lactam sensors and undergoes a typical
      acylation reaction in the active site of these proteins. The probe binds the
      class D carbapenemase OXA-24/40 with close to the same affinity as meropenem and
      undergoes a complete catalytic hydrolysis reaction. The visible light excitation
      and strong emission of fluorescein render this molecule a useful structure
      function probe through its application in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis assays as well as solution-based kinetic anisotropy assays.
      Its classification as a carbapenem beta-lactam and the position of its
      fluorescent modification render it a useful complement to other fluorescent beta
      lactams, most notably Bocillin FL. In this study, we show the utility of
      fluorescein-meropenem by using it to detect mutants of OXA-24/40 that arrest at
      the acyl-intermediate state with carbapenem substrates but maintain catalytic
      competency with penicillin substrates. 

PMID- 25058928
TI  - Highly sensitive fluorescence assay of T4 polynucleotide kinase activity and
      inhibition via enzyme-assisted signal amplification.
AB  - DNA phosphorylation catalyzed by polynucleotide kinase (PNK) is an indispensable
      process in the repair, replication, and recombination of nucleic acids. Here, an
      enzyme-assisted amplification strategy was developed for the ultrasensitive
      monitoring activity and inhibition of T4 PNK. A hairpin oligonucleotide (hpDNA)
      was designed as a probe whose stem can be degraded from the 5' to 3' direction by
      lambda exonuclease (lambda exo) when its 5' end is phosphorylated by PNK. So, the
      3' stem and loop part of hpDNA was released as an initiator strand to open a
      molecular beacon (MB) that was designed as a fluorescence reporter, leading to a
      fluorescence restoration. Then, the initiator strand was released again by the
      nicking endonuclease (Nt.BbvCI) to hybridize with another MB, resulting in a
      cyclic reaction and accumulation of fluorescence signal. Based on enzyme-assisted
      amplification, PNK activity can be sensitively and rapidly detected with a
      detection limit of 1.0*10(-4)U/ml, which is superior to those of most existing
      approaches. Furthermore, the application of the proposed strategy for screening
      PNK inhibitors also demonstrated satisfactory results. Therefore, it provided a
      promising platform for monitoring activity and inhibition of PNK as well as for
      studying the activity of other nucleases. 

PMID- 25058929
TI  - Discovery and optimization of 1,3,5-trisubstituted pyrazolines as potent and
      highly selective allosteric inhibitors of protein kinase C-zeta.
AB  - There is increasing evidence that the atypical protein kinase C, PKCzeta, might
      be a therapeutic target in pulmonary and hepatic inflammatory diseases. However,
      targeting the highly conserved ATP-binding pocket in the catalytic domain held
      little promise to achieve selective inhibition. In the present study, we
      introduce 1,3,5-trisubstituted pyrazolines as potent and selective allosteric
      PKCzeta inhibitors. The rigid scaffold offered many sites for modification, all
      acting as hot spots for improving activity, and gave rise to sharp structure
      activity relationships. Targeting of PKCzeta in cells was confirmed by reporter
      gene assay, transfection assays, and Western blotting. The strongly reduced cell
      free and cellular activities toward a PIF-pocket mutant of PKCzeta suggested that
      the inhibitors most likely bound to the PIF-pocket on the kinase catalytic
      domain. Thus, using a rigidification strategy and by establishing and optimizing
      multiple molecular interactions with the binding site, we were able to
      significantly improve the potency of the previously reported PKCzeta inhibitors. 

PMID- 25058930
TI  - Air quality in developing world disaster and conflict zones--the case of post
      earthquake Haiti.
AB  - Data on air quality are remarkably limited in the poorest of the world's
      countries. This is especially true for post-conflict and disaster zones, where
      international relief efforts focus largely on more salient public health
      challenges such as water and sanitation, infectious diseases, and housing. Using
      post-earthquake Haiti as the example case, this commentary explores air quality
      challenges in the developing world, highlighting concerns related to
      infrastructure damage from post-conflict and disaster settings. We contend that
      there is a growing and presently unmet need for further research and attention
      from the global health community to address these issues. 

PMID- 25058931
TI  - Water exposure assessment of aryl hydrocarbon receptor agonists in Three Gorges
      Reservoir, China using SPMD-based virtual organisms.
AB  - SPMD-based virtual organisms (VOs) were deployed at five to eight sites in the
      Three Gorges Reservoir (TGR), China for five periods in 2008, 2009 and 2011. The
      water exposure of aryl hydrocarbon receptor (AhR) agonists was assessed by the
      VOs. The chosen bioassay response for the extracts of the VOs, the induction of 7
      ethoxyresorufin-O-deethylase (EROD) was assayed using a rat hepatoma cell line
      (H4IIE). The results show that the extracts from the VOs could induce AhR
      activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) equivalent (TEQcal) accounted for <11% of the observed AhR
      responses (TEQbio). Unidentified AhR-active compounds represented a greater
      proportion of the TCDD equivalent in VOs from TGR. High TEQbio value in diluted
      extract and low TEQbio in concentrated extract of the same sample was observed
      suggesting potential non-additive effects in the mixture. The levels of AhR
      agonists in VOs from upstream TGR were in general higher than those from
      downstream reservoir, indicating urbanization effect on AhR agonist pollution.
      The temporal variation showed that levels of AhR agonists in 2009 and 2011 were
      higher than those in 2008, and the potential non-additive effects in the area
      close to the dam were also obviously higher in 2009 and 2011 than in 2008,
      indicating big changes in the composition of pollutants in the area after water
      level reached a maximum of 175 m. Although the aqueous concentration of AhR
      agonists of 0.8-4.8 pg TCDDL(-1) in TGR was not alarming, the tendency of
      accumulating high concentration of AhR agonists in VO lipid and existence of
      possible synergism or antagonism in the water may exhibit a potential hazard to
      local biota being exposed to AhR agonists.

PMID- 25058932
TI  - Ecotoxicity effects triggered in aquatic organisms by invasive Acer negundo and
      native Alnus glutinosa leaf leachates obtained in the process of aerobic
      decomposition.
AB  - The replacement of autochthonous tree species by invasive ones in coastal zones
      of freshwater bodies induces additional alteration of hydrochemical and
      microbiological characteristics due to decomposition of fallen leaves of non
      indigenous species, which can lead to ecotoxic response of the littoral biota.
      Leaves of invasive to Lithuania boxelder maple (Acer negundo) and autochthonous
      black alder (Alnus glutinosa) lost more than half of biomass and released stable
      amount of DOC (60-70 mg/L) throughout 90-day mesocosm experiment under aerobic
      conditions. This, along with the relatively small BOD7 values detected after some
      variation within the first month confirms effective biodegradation by fungi and
      bacteria. The ambient water was more enriched with different forms of N and P by
      decomposing boxelder maple than by alder leaves. During the first month, both
      leachates were more toxic to charophyte (Nitellopsis obtusa) at mortality and
      membrane depolarization levels, while later to two crustacean species. Biomarker
      response, H(+)-ATPase activity in membrane preparations from N. obtusa, was
      stronger for A. negundo. Generally, boxelder maple leaf leachates were more toxic
      to tested hydrobionts and this coincides with previous study on leaves of the
      same pair of tree species conducted under microaerobic conditions (Krevs et al.,
      2013).

PMID- 25058933
TI  - Possible future effects of large-scale algae cultivation for biofuels on coastal
      eutrophication in Europe.
AB  - Biodiesel is increasingly considered as an alternative for fossil diesel.
      Biodiesel can be produced from rapeseed, palm, sunflower, soybean and algae. In
      this study, the consequences of large-scale production of biodiesel from micro
      algae for eutrophication in four large European seas are analysed. To this end,
      scenarios for the year 2050 are analysed, assuming that in the 27 countries of
      the European Union fossil diesel will be replaced by biodiesel from algae.
      Estimates are made for the required fertiliser inputs to algae parks, and how
      this may increase concentrations of nitrogen and phosphorus in coastal waters,
      potentially leading to eutrophication. The Global NEWS (Nutrient Export from
      WaterSheds) model has been used to estimate the transport of nitrogen and
      phosphorus to the European coastal waters. The results indicate that the amount
      of nitrogen and phosphorus in the coastal waters may increase considerably in the
      future as a result of large-scale production of algae for the production of
      biodiesel, even in scenarios assuming effective waste water treatment and
      recycling of waste water in algae production. To ensure sustainable production of
      biodiesel from micro-algae, it is important to develop cultivation systems with
      low nutrient losses to the environment. 

PMID- 25058934
TI  - Human health risk assessment of the mixture of pharmaceuticals in Dutch drinking
      water and its sources based on frequent monitoring data.
AB  - The presence of pharmaceuticals in drinking water is a topic of concern. Previous
      risk assessments indicate that their low concentrations are very unlikely to pose
      risks to human health, however often conclusions had to be based on small
      datasets and mixture effects were not included. The objectives of this study were
      to a) investigate if pharmaceuticals in surface and polder water penetrate in
      drinking water, b) assess the lifelong exposure of consumers to pharmaceuticals
      via drinking water and c) assess the possible individual and mixture health risks
      associated with this exposure. To fulfill these aims, a 2-year set of 4-weekly
      monitoring data of pharmaceuticals was used from three drinking water production
      plants. The 42 pharmaceuticals that were monitored were selected according to
      their consumption volume, earlier detection, toxicity and representation of the
      most relevant therapeutic classes. Lifelong exposures were calculated from
      concentrations and compared with therapeutic doses. Health risks were assessed by
      benchmarking concentrations with provisional guideline values. Combined risks of
      mixtures of pharmaceuticals were estimated using the concept of Concentration
      Addition. The lifelong exposure to pharmaceuticals via drinking water was
      calculated to be extremely low, i.e. a few mg, in total corresponding to <10% of
      the dose a patient is administered on one day. The risk of adverse health effects
      appeared to be negligibly low. Application of Concentration Addition confirmed
      this for the mixture of pharmaceuticals simultaneously present. The investigated
      treatment plants appeared to reduce the (already negligible) risk up to 80%. The
      large available monitoring dataset enabled the performance of a realistic risk
      assessment. It showed that working with maximum instead of average concentrations
      may overestimate the risk considerably. 

PMID- 25058935
TI  - Quick and efficient co-treatment of Zn(2+)/Ni(2+) and CN(-) via the formation of
      Ni(CN)4(2-) intercalated larger ZnAl-LDH crystals.
AB  - The wide use of metal electroplating involving CN(-) necessitates the cost
      effective treatment of both CN and metals (Zn, Cu, Ni etc.). In this research, we
      developed a novel strategy - Ni(2+)-assisted layered double hydroxide (LDH)
      precipitation - to simultaneously remove aqueous CN and Zn/Ni metals. The
      strategy is to convert CN(-)/Zn(CN)4(2-) to Ni(CN)4(2-) first, and then to
      quickly precipitate Ni(CN)4(2-)/CN(-) into LDH crystals. The conversion has been
      clearly evidenced by the change of CN characteristic FTIR bands of Zn-CN solution
      before and after adding Ni(NO3)2. The intercalation and efficient removal of CN
      have also been confirmed through the formation of LDH crystals XRD and SEM. In
      particular, a set of optimized experimental factors has been obtained by
      investigating their effects on CN removal efficiency in the simulated tests.
      Remarkably, over 95% CN were removed with high removal efficiencies of metals.
      Our results thus suggest that the current strategy is a quick, efficient and
      promising way to simultaneously treat both Ni and metals/CN rich electroplating
      wastewaters. 

PMID- 25058936
TI  - Evaluation on joint toxicity of chlorinated anilines and cadmium to
      Photobacterium phosphoreum and QSAR analysis.
AB  - The individual IC50 (the concentrations causing a 50% inhibition of
      bioluminescence after 15min exposure) of cadmium ion (Cd) and nine chlorinated
      anilines to Photobacterium phosphoreum (P. phosphoreum) were determined. In order
      to evaluate the combined effects of the nine chlorinated anilines and Cd, the
      toxicities of chlorinated anilines combined with different concentrations of Cd
      were determined, respectively. The results showed that the number of chlorinated
      anilines manifesting synergy with Cd decreased with the increasing Cd
      concentration, and the number manifesting antagonism decreased firstly and then
      increased. The joint toxicity of mixtures at low Cd concentration was weaker than
      that of most binary mixtures when combined with Cd at medium and high
      concentrations as indicated by TUTotal. QSAR analysis showed that the single
      toxicity of chlorinated anilines was related to the energy of the lowest
      unoccupied molecular orbital (ELUMO). When combined with different concentrations
      of Cd, the toxicity was related to the energy difference (EHOMO-ELUMO) with
      different coefficients. Van der Waals' force or the complexation between
      chlorinated anilines and Cd had an impact on the toxicity of combined systems,
      which could account for QSAR models with different physico-chemical descriptors. 

PMID- 25058937
TI  - An electrochemical immunosensor for ultrasensitive detection of carbohydrate
      antigen 199 based on Au@Cu(x)OS yolk-shell nanostructures with porous shells as
      labels.
AB  - A novel and sensitive electrochemical immunosensor for ultrasensitive detection
      of pancreatic cancer biomarker carbohydrate antigen 199 (CA199) was proposed by
      using Au@Cu(x)OS yolk-shell nanostructures with porous shells as labels for
      signal amplification. Au@Cu(x)OS yolk-shell nanostructures exhibit high
      electrocatalytic activity toward the reduction of hydrogen peroxide (H2O2) as
      analytical signal. Moreover, secondary antibody (Ab2) can adsorb on the surface
      of Au@Cu(x)OS with porous shells which has large surface area and could greatly
      increase the probability of Ab2-antigen interactions thereby leading to higher
      sensitivity. Reduced graphene oxide-tetraethylene pentamine (rGO-TEPA),
      containing abundant amine groups, was supported Au nanoparticles as a support
      platform to immobilize the primary antibody (Ab1). The resulting sensing
      interface of rGO-TEPA/AuNPs could provide a large electroconductive surface area,
      allowing high loadings of the biological recognition elements as well as the
      occurrence of electrocatalytic and electron-transfer processes. Under optimal
      conditions, the immunosensor exhibited a wide linear response to CA199 ranging
      from 0.001 to 12 U/mL with a low detection limit of 0.0005 U/mL. The designed
      immunosensor displayed good precision, high sensitivity, acceptable stability and
      reproducibility, and has been applied to the analysis of serum with satisfactory
      results. The proposed method provides a new promising platform of clinical
      immunoassay for other biomolecules.

PMID- 25058938
TI  - Highly sensitive and selective colorimetric detection of glutathione based on Ag
      [I] ion-3,3',5,5'-tetramethylbenzidine (TMB).
AB  - Glutathione (GSH) plays an important role in the biological system and serves
      many cellular functions. Since all of the biothiols possess similar functional
      groups, it is still challenging to selectively detect GSH over cysteine (Cys) and
      homocysteine (Hcy). In this work, a novel and simple colorimetric method for
      discriminative detection of glutathione (GSH) over Cys and Hcy is developed. The
      proposed method is based on the fact that Ag [I] ion could oxidize 3,3',5,5',
      tetramethylbenzidine (TMB) to the oxidized TMB to induce a blue color and an
      absorption peak centered at 652 nm. However, the introduction of GSH could cause
      the reduction of oxidized TMB and it could also combine with Ag(+), both of which
      result in a blue color fading and a decrease of the absorbance at 652 nm. Based
      on this finding, we propose a method to qualitatively and quantitatively detect
      GSH by naked eyes and UV-vis spectroscopy, respectively. The proposed method
      shows a low detection limit of 0.1 uM by naked eyes and 0.05 uM with the help of
      UV-vis spectroscopy. In addition, this method has great potential in
      discriminatively detecting GSH over other amino acid and biothiols. More
      importantly, this method is simple and fast without the preparation of
      nanomaterials and has also been successfully applied to the detection of GSH in
      biological fluids.

PMID- 25058939
TI  - Overcoming the aggregation problem: a new type of fluorescent ligand for ConA
      based glucose sensing.
AB  - Competitive binding assays based on the lectin Concanavalin A (ConA) have
      displayed significant potential to serve in continuous glucose monitoring
      applications. However, to date, this type of fluorescent, affinity-based assay
      has yet to show the stable, glucose predictive capabilities that are required for
      such an application. This instability has been associated with the extensive
      crosslinking between traditionally-used fluorescent ligands (presenting multiple
      low-affinity moieties) and ConA (presenting multiple binding sites) in free
      solution. The work herein introduces the design and synthesis of a new type of
      fluorescent ligand that can avoid this aggregation and allow the assay to be
      sensitive across the physiologically relevant glucose concentration range. This
      fluorescent ligand (APTS-MT) presents a single high-affinity trimannose moiety
      that is recognized by ConA's full binding site and a fluorophore that can
      effectively track the ligand's equilibrium binding via fluorescent anisotropy.
      This is confirmed by comparing its measured fluorescent lifetime to
      experimentally-determined rotational correlation lifetimes of the free and bound
      populations. Using an assay comprised of 200 nM APTS-MT and 1 uM ConA, the
      fluorescence anisotropy capably tracks the concentration of monosaccharides that
      are known to bind to ConA's primary binding site, and the assay displays a MARD
      of 6.5% across physiologically relevant glucose concentrations. Ultimately, this
      rationally-designed fluorescent ligand can facilitate the realization of the full
      potential of ConA-based glucose sensing assays and provide the basis for a new
      set of competing ligands to be paired with ConA.

PMID- 25058940
TI  - Fluorescent carbon nanoparticles for the fluorescent detection of metal ions.
AB  - Fluorescent carbon nanoparticles (F-CNPs) as a new kind of fluorescent
      nanoparticles, have recently attracted considerable research interest in a wide
      range of applications due to their low-cost and good biocompatibility. The
      fluorescent detection of metal ions is one of the most important applications. In
      this review, we first present the general detection mechanism of F-CNPs for the
      fluorescent detection of metal ions, including fluorescence turn-off,
      fluorescence turn-on, fluorescence resonance energy transfer (FRET) and
      ratiometric response. We then focus on the recent advances of F-CNPs in the
      fluorescent detection of metal ions, including Hg(2+), Cu(2+), Fe(3+), and other
      metal ions. Further, we discuss the research trends and future prospects of F
      CNPs. We envision that more novel F-CNPs-based nanosensors with more accuracy and
      robustness will be widely used to assay and remove various metal ions, and there
      will be more practical applications in coming years. 

PMID- 25058941
TI  - Bioimpedance monitoring of 3D cell culturing--complementary electrode
      configurations for enhanced spatial sensitivity.
AB  - A bioimpedance platform is presented as a promising tool for non-invasive real
      time monitoring of the entire process of three-dimensional (3D) cell culturing in
      a hydrogel scaffold. In this study, the dynamics involved in the whole process of
      3D cell culturing, starting from polymerisation of a bare 3D gelatin scaffold, to
      human mesenchymal stem cell (MSC) encapsulation and proliferation, was monitored
      over time. The platform consists of a large rectangular culture chamber with four
      embedded vertical gold plate electrodes that were exploited in two- and three
      terminal (2T and 3T) measurement configurations. By switching between the
      different combinations of electrode couples, it was possible to generate a
      multiplexing-like approach, which allowed for collecting spatially distributed
      information within the 3D space. Computational finite element (FE) analysis and
      electrochemical impedance spectroscopic (EIS) characterisation were used to
      determine the configurations' sensitivity field localisation. The 2T setup gives
      insight into the interfacial phenomena at both electrode surfaces and covers the
      central part of the 3D cell culture volume, while the four 3T modes provide focus
      on the dynamics at the corners of the 3D culture chamber. By combining a number
      of electrode configurations, complementary spatially distributed information on a
      large 3D cell culture can be obtained with maximised sensitivity in the entire 3D
      space. The experimental results show that cell proliferation can be monitored
      within the tested biomimetic environment, paving the way to further developments
      in bioimpedance tracking of 3D cell cultures and tissue engineering. 

PMID- 25058942
TI  - Leukemic marker detection using a spectro-polarimetric surface plasmon resonance
      platform.
AB  - In this paper, we present a proof of concept screening for monoclonal
      immunoglobulin as a leukemia tumor marker using a surface plasmon resonance (SPR)
      bio-sensing platform. This screening method is based on measurements of
      immunoglobulin levels in human serum and the determination of the relative
      concentrations of kappa and lambda light chains. The kappa/lambda ratio is used
      to determine the presence of monoclonal immunoglobulin. Tests have been performed
      using standard solutions of immunoglobulins and serum samples from patients with
      known leukemic diagnoses. This platform has a resolution of 5*10(-7) refractive
      index unit (RIU) per channel, which is up to 10 times better than other SPR
      imaging systems for multi-sensing applications. The results obtained with this
      technique are in agreement with those acquired using conventional methods for
      immunoglobulin detection, indicating that our polarimetric SPR platform should be
      suitable for a cheap and efficient tool for early leukemia biomarker screening
      and monitoring applications. 

PMID- 25058943
TI  - Monitoring recombinant human erythropoietin abuse among athletes.
AB  - The illegal administration of recombinant human erythropoietin (rHuEPO) among
      athletes is largely preferred over blood doping to enhance stamina. The advent of
      recombinant DNA technology allowed the expression of EPO-encoding genes in
      several eukaryotic hosts to produce rHuEPO, and today these performance-enhancing
      drugs are readily available. As a mimetic of endogenous EPO (eEPO), rHuEPO
      augments the oxygen carrying capacity of blood. Thus, monitoring the illicit use
      of rHuEPO among athletes is crucial in ensuring an even playing field and
      maintaining the welfare of athletes. A number of rHuEPO detection methods
      currently exist, including measurement of hematologic parameters, gene-based
      detection methods, glycomics, use of peptide markers, electrophoresis,
      isoelectric focusing (IEF)-double immunoblotting, aptamer/antibody-based methods,
      and lateral flow tests. This review gleans these different strategies and
      highlights the leading molecular recognition elements that have potential roles
      in rHuEPO doping detection. 

PMID- 25058944
TI  - Preface.

PMID- 25058945
TI  - Preface.

PMID- 25058946
TI  - Francis Edgar Hunter 27th May 1930-30th September 2013.

PMID- 25058947
TI  - Differential diagnosis of foot drop: foot drop stroke syndrome.

PMID- 25058948
TI  - [Pay attention to diagnosis and treatment of chronic lateral ankle instability].

PMID- 25058949
TI  - [Micromovement characteristic of distal tibiofibular joints in normal Chinese].
AB  - OBJECTIVE: To analyze micromovement of distal tihiofihular joints in different
      motion range of ankle joint ,and define the micromovement characteristic and
      range of distal tibiofihular joints. METHODS: Twelve normal Chinese were chosen.
      There were 9 males and 3 females, aged from 19 to 37 years old with an average
      (26.5 +/- 0.5) years. Detection terminals of laser photographic scanner were
      installed near the highest point between medial malleolus and lateral malleolos,
      the change of detection terminals on the position of dorsiflex, extension,
      introversion and eversion of ankle joint were scanned by 3D-laser scanner. The
      displacement of two detection terminals on the X ,Y and Z-axis (X-axis stands for
      the vertical-axis between coronal plane and Z-axis Y-axis stands for the vertical
      axis between sagittal plane and Z-axis Z-axis stands for macroaxis of tibia).
      RESULTS: Along with increased range of motion on the position of dorsiflex
      ,extension, introversion and eversion of ankle joint, the range of micromovement
      of distal tibiofibolar joints increased too. The max-displacement of X, Y and Z
      were respectively (1.04 +/- 0.12) mm, (1.70 +/- 0.16) mm and--(0.87 +/- 0.10) mm.
      CONCLUSION: 3D-laser scanner can be used to determine the detailed displacement
      of distal tibiofibolar joint on the X , Y and Z, and measure the motion of distal
      tibiofibular joint. The method can be used to study the pathologic change of
      distal tibiofibular joint ,and provide basic biomechnics data for internal fixtor
      fitting for the characteristic of distal tibiofibular joint.

PMID- 25058950
TI  - [Rosai-Dorfman disease in sketetal system: a case report].

PMID- 25058951
TI  - [Case-control study on bone setting manipulation for the treatment of over degree
      II supination-eversion fractures of ankle joint].
AB  - OBJECTIVE: To explore therapeutic effects of bone setting manipulation for the
      treatment of over degree II supination-eversion fractures of ankle,and analyze
      manipulative reduction mechanism. METHODS: From 2005 to 2008, 95 patients with
      over degree II supination-eversion fractures of ankle were treated respectively
      by manipulation and operation. There were 43 cases [11 males and 32 females with
      an average age of (44.95 +/- 12.65) years] in manipulation group, and 2 cases
      were degree II, 11 cases were degree III, and 30 cases were degree IV. There were
      52 cases [21 males and 31 females with an average age of (39.96 +/- 13.28) years]
      in operative group,and 6 cases were degree II, 18 cases were degree III, and 28
      cases were degree IV. Bone setting manipulation and hard splint external fixation
      were applied to manipulative group. Operative reduction internal fixation was
      performed in operative group. X-ray was used to evaluate reduction of fracture
      before and after treatment, 2 months after treatment. Ankle joint function was
      evaluated according to Olerud-Molander scoring system after 6 months treatment.
      RESULTS: All patients were followed up with good reduction. Three cases occurred
      wound complication in operative group, but not in manipulative group. In
      manipulation group, 19 cases got excellent results, 20 cases good and 4 cases
      fair; while in operative group, 30 cases got excellent results, 20 cases good and
      2 cases poor. There were no significant differences in fracture reduction and
      ankle joint function recovery between two groups (P > 0.05). Efficacy of
      operative treatment was better than that of manipulative treatment at degree IV
      fracture (P < 0.05). CONCLUSION: Bone setting manipulation is a good method for
      treating supination-eversion ankle joint fractures, which has advantages of
      simple and safe operation, reliable efficacy. For ankle join fracture at degree
      IV, manipulative reduction should be adopted earlier, and operative treatment
      also necessary

PMID- 25058952
TI  - [Clinical effects of steel plate fixation for the failure of arthrodesis of ankle
      by screw fixation].
AB  - OBJECTIVE: To observe the therapeutic effects of steel plate fixation after the
      failure of arthrodesis of ankle by screw fixation. METHODS: From August 2001 to
      October 2011, 15 patients were with steel plate fixation after failure of
      arthrodesis of ankle by screw fixation. Among patients, 9 cases were males and 6
      cases were females,ranging age from 40 to 65 years old with the average of 56
      years old. Ten cases were in left and 5 cases were in right. Screws were removed
      and steel plate was fixed intraoperatively, and plaster external fixation for
      postoperation. Clincal effect were evaluated according to AOFAS scoring system
      from pain, waliking ability and aligment before and after operation, and X-ray
      was used to evaluate joint fusion after operation. RESULTS: All patients were
      followed up, and the duration ranged from 4 months to 4 years with an average of
      2 years. The incison were healed in stage I. No ankle pain,injury of blood vessel
      and nerve,infection and farilure of internal fixation occuerred. The AOFAS score
      increased from 36.86 +/- 8.32 preoperatively to 85.09 +/- 4.65 (t = -26.366, P =
      0.000). CONCLUSION: Steel plate fixation after the failure of ankle arthrodesis
      of screw fixation has the advantages of rigid stability, simple manipulation and
      high success rate, less pain, perfect recovery.

PMID- 25058953
TI  - [Treatment of syndesmosis diastasis with shape memory staple fixation in ankle
      fractures].
AB  - OBJECTIVE: To explore operative method in the treatment of syndesmosis injury of
      ankle fractures. METHODS: Twenty-four patients with ankle fractures and
      syndesmosis diastasis were treated with shape memory fracture staples, including
      10 males and 14 females ranging in age from 19 to 71 years, with an average of 43
      years. All patients were diagnosised with history, body examination and image
      data and were operated according to classification of Lauge-Hansen. RESULTS: All
      patients were followed up from 6 to 28 months with an average of 16 months, and
      all fractures healed, with a mean time 9.2 (8 to 14) weeks. Only one case had
      radiological and clinical manifestations of traumatic arthritis, but no breakage
      of shape memory fracture staple in all cases. Sixteen patients got excellent
      results, good in 5, fair in 2, poor in 1. CONCLUSION: Shape memory staple
      fixation for the treatment of syndesmosis diastasis in ankle fractures not only
      can perseve the physical motion of ankles, but also be remove earlier before
      weight bearing.

PMID- 25058954
TI  - [Treatment of Gustilo III distal tibiofibula fractures through trans-fibular
      anterior-lateral approach].
AB  - OBJECTIVE: To explore the methods and therapeutic effects of trans-fibular
      anterior-lateral approach combined with external fixation in the treatment of
      Gustilo III distal tibiofibula fractures. METHODS: From 2007 to 2010,9 patients
      including 7 males and 2 females with the mean age of 40 years(ranging from 29 to
      51 years). All patients received internal fixation of fibula after debridement on
      the first phase, external fixator were used to fix tibia across ankle joint, and
      removed after successful skin graft; The second phase tibia was used to fix
      through the lateral incision used in phase I. Early functional exercise was
      encouraged ,the union condition and functional results of the ankle joint was
      evealuated. The criteria of the AOFAS Foot and Ankle Surgery was used to evaluate
      the effects. RESULTS: All patients were followed up,and the duration ranged for 8
      to 37 months(averaged 21 months). Nine patients were achieved bony union, the
      average healing time was 24 weeks. No plate rupture or screw loosening was found.
      According to the AOFAS Foot and Ankle Surgery evaluation system, 3 cases got
      excellent results, 4 good cases and 2 fair. CONCLUSION: Trans-fibular anterior
      lateral approach combined with external fixation for Gustilo III distal
      tibiofibula fractures can receive satisfactory reset, debond ankle joint eralier
      and imporove the clinical effects.

PMID- 25058955
TI  - [Replantation of fingertip amputation in lack of availability of intravenous
      anastomosis].
AB  - OBJECTIVE: To discuss the replantation of fingertip amputation in lack of
      availability of intravenous anastomosis. METHODS: From November 2009 to November
      2010, 86 patients (104 fingers) with fingertip amputation were treated with
      replantatioin, including 64 males and 22 females, with an average age of 26 years
      ranging from 2 to 64 years. The time from injury to therapy was from 30 min to 12
      h, time of broken finger ischemia was from 2.5 to 12 h. Preoperative examination
      showed no obvious abnormalities. Four different replantation methods were
      selectively applied to these 104 amputated fingertips of 86 cases: (1)
      replantation with anastomosis of single or bilateral proper digital artery in 37
      fingers; (2) replantation with arteriovenous bypass in 27 fingers; (3)
      replantation with exclusive anastomosis of digital artery in 24 fingers; (4)
      replantation with removing the palmar pocket method in 16 fingers. RESULTS: One
      hundred and two of 104 amputated fingertips were survived. Among these survived
      fingers,75 cases (92 fingers) were followed-up for 6 to 24 months. According to
      the assessment standard of Chinese Medical Association of Hand Surgery, the
      results were excellent in 52 cases, good in 19, poor in 4. CONCLUSION: It
      benefits to expand the indications and improve the survival rate of replantation
      of fingertip amputation with the correct choice of different replantation methods
      according to the injury situation of the broken fingertip artery after
      debridement under the microscope.

PMID- 25058956
TI  - [Application of vacuum sealing drainage in open ankle fracture and dislocation].
AB  - OBJECTIVE: To investigate therapeutic effects of vacuum sealing drainage (VSD) in
      the treatment of soft tissue defect combined with tendon and bone exposure.
      METHODS: From October 2007 to February 2011, 397 patients (412 feet) with open
      ankle fracture and dislocation combined with soft tissue defected were treated by
      VSD. There were 301 males and 96 females with an average age of 36 years (ranging
      age from 20 to 73 years). According to AO classification, 74 feet were type I,
      211 feet were type II, 108 feet were type III and 19 feet were type IV. The mean
      time from injury to operation was 5.6 h ( 2 to 12 h). The mean treatment time of
      was 10 months (4 to 19 months). RESULTS: One hundred and forty-one patients were
      primarily healed, 97 patients were sutured at stage II. Split-thick skin grafting
      was performed at stage II was performed in 103 patients; free flap
      transplantation was performed in 25 patients. Three of the 34 patients with
      infection were removed steel plate; Eviscerate flap coverage wound was performed
      in 14 patients caused by the first metatarsal bone exposure; Toe amputation were
      performed in 22 cases caused by toes necrosis. Tarsometatarasl joints
      perforators' surgery was performed in 10 patients with forefeet necrosis. Thirty
      hundred and six patients were followed up from 3 to 20 months (averaged 10
      months). The wounds healed well. CONCLUSION: VSD for soft tissue defects caused
      by ankle injury is a simple and effective method, but can not replace debridement
      and transfer flap.

PMID- 25058957
TI  - [Biomechanical comparison of Evans procedure and Chrisman-Snook technique for the
      treatment of II degree lateral collateral ligament of ankle joint].
AB  - OBJECTIVE: To measure the stability of Evans procedure and Chrisman-Snook
      technique in the treatment of II degree lateral collateral ligament of ankle
      joint, and provide basis for treatment and prognosis. METHODS: From July 2008 to
      June 2009,18 frozen corpes were collected, including 10 males and 8 females, with
      an average age of fresh 39.3 +/- 11.2 years. The frozen corpes were randomly
      divided into three group, including normal controls(group A), Evans procedure
      (group B) and Chrisman-Snook technique ( group C), 6 specimens in each group.
      Anterior talofibular ligament and calcaneofibular ligament were cut off to cause
      II degree lateral collateral ligament in group B and C. Evans procedure or
      Chrisman-Snook technique were applied to restore lateral collateral ligament, and
      measure biomechnics. The displacement of tibiotalar joint and subtalar joint were
      observed. RESULTS: (1) The lateral stress results of tibiotalar joint showed the
      displacement by Evans procedure (group B) was greater than other groups (P <
      0.0001). There were no significant differences between group A and C (P > 0.05).
      (2) The lateral stress results of subtalar joint showed the displacement by Evans
      procedure (group B) was greater than other groups (P< 0.0001). There were no
      significant differences between group A and C (P > 0.05). CONCLUSION: Ankle
      instability is caused by ankle joint lateral collateral ligament injury. Chrisman
      Snook technique is better than Evans procedure in stability on the early stage of
      ankle joint restoration, and conform to principle of biomechanics.

PMID- 25058958
TI  - [Biomechanical effect of anterior lower tibiofibular ligament rupture on
      tibiotalar articular surface].
AB  - OBJECTIVE: To investigate the changes between pressure of trochlea of talus
      surface and distribution of area after anterior lower tibiofibular ligament
      rupture, and provide basis for treating anterior lower tibiofibular ligament
      rupture. METHODS: Six fresh adult ankle joint specimens (4 males and 2 females,
      ranging age from 25 to 60 years, with an average of 44.6 years) were adopted. The
      specimens were removed from skin and muscles, remained ankle joint capsule,
      medial and lateral ligaments and anteroinferior tibiofibular ligament. The ankle
      joint was fixed with a special fixture in neutral position. Pressure sensitive
      film (700 N axial load ) was respectively used to measure mean pressure, peak
      pressure and stress distribution area of the upper articular facet of talar
      trochlea of the normal ankle joint and the ankle joint with anterioinferior
      tibiofibular ligament rupture. RESULTS: The stress distribution areas of the
      control group and the ruptured group were respectively (367.8 +/- 54.0) mm2 and
      (386.0 +/- 53.7) mm2; the mean pressures were respectively (1.40 +/- 0.12) MPa
      and (1.70 +/- 0.35) MPa; the peak pressures were respectively (2.60 +/- 0.33) MPa
      and (3.20 +/- 0.32) MPa. The experimental results showed that the change in
      stress distribution area after anterioinferior tibiofibular ligament rupture was
      not significant (t = 0.021, P = -0.983). When stress distribution changed, the
      region of stress concentration transferred to poster lateral,and mean pressure (t
      = 4.140, P = 0.020) and peak pressure (t = 3.169, P = 0.010) increased
      significantly. CONCLUSION: When anterior lower tibiofibular ligament rupture
      occurs, mean pressure,peak pressure and stress distribution of pressure of
      trochlea of talus surface is changed, which may cause traumatic arthritis, and
      surgical treatment is considerably used to restore normal anatomy.

PMID- 25058959
TI  - [Effects of surface roughness of bone cements on histological characteristics of
      induced membranes].
AB  - OBJECTIVE: To explore surface roughness of bone cement and surround tissue on
      histological characteristic of induced membranes. METHODS: Bone cements with
      smooth and rough surface were implanted in radius bone defect, intramuscular and
      subcutaneous sites of rabbits, and formed induced membranes. Membranes were
      obtained and stained (HE) 6 weeks later. Images of membrane tissue were obtained
      and analyzed with an automated image analysis system. Five histological
      parameters of membranes were measured with thickness,area,cell density,ECM
      density and microvessel density. Double factor variance analysis was used to
      evaluate the effect of the two factors on histological characteristics of induced
      membranes. RESULTS: Membranes can be induced by each kind of bone cement and at
      all the three tissue sites. In histological parameters of thickness,area and
      micro vessel,there were significant differences among the membranes induced at
      different tissue sites (P = 0.000, P = 0.000, P = 0.000); whereas, there were no
      significant differences in histological parameters of cell density and ECM
      density (P = 0.734, P = 0.638). In all five histological parameters of membranes,
      there were no significant differences between the membranes induced by bone
      cements with different surface roughness (P = 0.506, P = 0.185, P = 0.883, P =
      0.093, P = 0.918). CONCLUSION: Surround tissue rather than surface roughness of
      bone cements can affect the histological characteristics of induced membranes.
      The fibrocystic number, vascularity, mechanical tension and micro motion of the
      surround tissue may be closely correlated with the histological characteristics
      of induced membranes.

PMID- 25058960
TI  - [Effects of vertebral height restoration of vertebroplasty for osteoporotic
      vertebra compression fractures].
AB  - OBJECTIVE: To evaluate the effect of vertebral height restoration of
      vertebroplasty for osteoporotic vertebra compression fractures (VCFs). METHODS:
      From October 2004 to June 2007, a total of 37 patients with 40 VCFs were treated
      by vertebroplasty. There were 12 males and 25 females with a mean age of (72.4 +/
      12.7) years (ranged, 48 to 87). Pain easement state was evaluated by visual
      analog scale (VAS) before and after operation, as well as in followed-up.
      Preoperative and postoperative vertebral height, kyphosis angle at fractured
      levels were measured on X-rays. RESULTS: All of patients were followed-up for 12
      to 47 months (averaged, 35.8 +/- 9.6). The VAS score was 8.4 +/- 1.6 before
      operative, 2.1 +/- 1.2 at the 2nd day after operative, there were significant
      difference between pre-and postoperative (P < 0.05); the average follow-up VAS
      was 1.6 +/- 0.9, there were significant difference as compared with the
      preoperative (P < 0.05). Lateral X-ray showed that the preoperative degree of
      vertebral height in the of anterior and middle vertebral were (72.0 +/- 10.6)%
      and (68.0 +/- 15.6)%, and postoperative were (76.0 +/- 8.6)% and (73.0 +/-6.1)%,
      respectively. There were no significant difference in vertebral height between
      preoperative and postoperative. The vertebral kyphosis angle was corrected from
      preoperative (7.8 +/- 2.7) degree to postoperative (8.1 +/- 2.3) degree.
      CONCLUSION: Vertebroplasty is a safe and effective method for treatment of
      osteoporotic VCFs, it can relieve the pain effectively. Failure to restore
      vertebaral height does not seem to interfere with the excellent pain management.

PMID- 25058961
TI  - [Comparison between surgical and conservative treatment for postoperative lumbar
      discitis].
AB  - OBJECTIVE: To compare therapeutic effects between surgical and conservative
      treatment for postoperative lumbar discitis. METHODS: From January 2004 to
      January 2009, 41 patients (17 males and 24 females ranging the age from 37 to 68
      years with an average of 53.6 years) with postoperative lumbar discitis were
      retrospectively studied and divided into two groups. There were 19 patients in
      operation group, 22 patients in conservative group. Clinical data and
      features,image data, laboratory examinations, antibiotics utilization, hospital
      stays and sequelae were recorded and analyzed. Visual analogue scales system
      (VAS) and Oswestry disability index (ODI) were applied to evaluate therapeutic
      effects. RESULTS: All patients were followed up over 2 years. Imaging revealed
      good bone fusion and no occurrence of discitis. VAS score and ODI at 1 month, 1
      year and 2 years were significantly improved after treatment (P < 0.01). While
      VAS and ODI in operation group at 1 month were improved more than that of
      conservative group (P < 0.01), and there was no significant difference between
      two groups at 1 year and 2 years (P > 0.01). CONCLUSION: Surgical and
      conservative treatment for postoperative lumbar discitis is effective. Surgical
      treatment is superior to conservative treatment in a short time, while
      conservative treatment can achieve long-term satisfactory curative effects.

PMID- 25058962
TI  - [Case-control study on suspine rotation manipulation for the treatment of lumbar
      disc herniation].
AB  - OBJECTIVE: To compare therapeutic effects between suspine rotation and flexion
      manipulation for treating lumbar disc herniation. METHODS: From December 2008 to
      January 2011, 134 patients with lumbar disc herniation were treated, including 74
      males and 60 females,ranging in age from 17 to 67 years,33 patients with age over
      50 years old. According to diagnosis the ladder of the 9 cases bulging type, 74
      hernia type, 51 cases free type. The patients were randomly divided into
      treatment group ( 69 cases) and control group (65 cases). All the patients were
      treated with the three-dimensional computer-controlled traction therapeutic
      apparatus,with continued traction for 20 minutes. After traction, flexion
      manipulation and rotat-ing manipulation were respectively adopted in treatment
      group and control group (on alternate days one time, 3 times as a course of
      treatment). The symptoms and signs (including back pain and discomfort, lower
      limb pain and numbness, powerless urination and defecation,numbness in perineum,
      straight-leg raising degree,ability of lower extremity walking,work and live) of
      patients were observed after treatment. RESULTS: All patients were followed up
      for 0.5 to 6 months with an average of 1.1 months. After treatment, the symptoms
      and signs of patients have significantly improved (P < 0.01), but the symptomes
      of powerless urination and defecation,numbness in perineum was not improved
      obviously (P>0.05). Forty-two of 69 patients in treatment group got excellent
      result, moderate in 20, poor in 7; Twenty of 65 patients in control group got
      excellent result, moderate in 25,poor in 20. CONCLUSION: The whole effect of
      lumbar backwards rotation manipulation is more satisfactory than flexsion
      manipulation for treating lumbar intervertebral disc herniation. But spinning
      force and times should be noticed.

PMID- 25058963
TI  - [Significance of preoperative color doppler flow imaging for screening deep vein
      thrombosis in upper limbs fracture].
AB  - OBJECTIVE: To explore significance of preoperative color Doppler flow imaging
      (CDFI) for screening deep vein thrombosis in upper limbs fracture. METHODS: From
      January 2009 to December 2011, 1200 patients with upper limb fracture caused by
      trauma were respectively analyzed. There were 833 males and 367 females,ranging
      from 20 to 78 (mean 41.94 +/- 15.41) years. All patients had swelling and pain in
      injured limbs when enrolled. CDFI was used to examine upper limbs vein at 3 to 10
      d after improvement of swelling, 1 day before reduction. Relationship among
      occurrence of thrombosis, gender, age and fracture sites were analyzed. Patients
      with DVT were analyzed with respective study to decide whether combined with
      diabetes, hypertension and hyperlipidemia. RESULTS: All patients were checked by
      CDFI,which confirmed 9 cases with DVT. The rate of thrombosis was 0.75%, women
      than men (P < 0.01). The risk of blood clots occurred over 30 years, and the
      occurrence of thrombosis in humerus fracture was higher than radius ulnar
      fracture. One of 9 patients combined with hypertension and hyperlipidemia, 1 case
      combined with diabetes, and 7 cases with no complication. CONCLUSION: Upper
      trauma fracture may occur deep vein thrombosis; CDFI should be used to check DVT
      in qualified hospital,which can maintain medical safety,decrease occurrence of
      medical disputes, and ganrantee patient's safety.

PMID- 25058964
TI  - [Retrospective study on volume of bone cement injection for concurrent of
      fracture after thoracolumbar vertebraes kyphoplasty].
AB  - OBJECTIVE: To explore relationship between volume of bone cement injection and
      concurrent of fracture after thoracolumbar osteoporotic vertebral fracture
      treated by percutaneous kyphoplasty (PKP). METHODS: From January 2006 to December
      2008,68 patients with thoracolumbar osteoporotic vertebral fracture treated by
      PKP were retrospectively analyzed. Among them, 30 patients with less than 3 ml
      bone cement injection (mean 2.5 ml, low group), including 11 males and 19
      females, with an average age of (85.0 +/- 8.5) years (ranging for 60 to 91); 38
      cases with over 4 ml bone cement injection (mean 4.5 ml, large group), including
      15 males and 23 females,with an average age of (86.0 +/- 9.2) years (ranging for
      60 to 93). Factors of concurrent vertebral fractures were observed during follow
      up. RESULTS: All patients were followed up from 3.4 to 5.1 years with an average
      of 3.8 years. Thirteen patients (43.3%) co-occurred fracture in low group,among
      which strengthened concurrent vertebral fracture occurred in 1 case,upper and
      lower section adjacent vertebral fracture in 8 cases,distal segment of vertebral
      fracture in 4 cases; while 18 patients (47.3%) co-occurred fracture in large
      group,among which strengthened concurrent vertebral fracture occurred in 2 cases,
      upper and lower section adjacent vertebral fracture in 10 cases,distal segment of
      vertebral fracture in 6 cases. No significant difference between two groups (P >
      0.05). CONCLUSION: Bone cement injection is not main influence factors for
      treating concurrent of fracture after thoracolumbar osteoporotic vertebral
      fracture by PKP. Concurrent fracture mainly relates with progress of
      osteoporosis, the volume of injection volume may appropriately over the volume of
      balloon.

PMID- 25058965
TI  - [Surgical selection and efficacy assessment for membranous urethral trauma caused
      by pelvic fracture].
AB  - OBJECTIVE: To explore selection and efficacy assessment for membranous urethral
      trauma caused by pelvic fracture. METHODS: From June 2000 to August 2010, 72
      patients with membranous urethral trauma caused by pelvic fracture were selected.
      There were 46 males and 26 females,ranging age from 26 to 62 years (averaged 35.2
      years). The time from injury to hospitalization time was 1 to 3 hours. According
      to Tile pelvic fracture classification, there were 8 patients with type A, 45
      patients with type B, 19 patients with type C. Thirty of the 35 patients with
      partial rupture of posterior urethral were treated by catheterization,5 patients
      treated by rupture anastomosis on the stage I combined with cystostomy; 25 of the
      37 patients with complete rupture of posterior urethra were treated by early
      realignment, and 12 patients were treated by cystostomy. Urinary incontinence,
      impotence and urethrostenosis were evaluated. RESULTS: All patients were followed
      up for 5 to 10 years (mean 7.7 years). Incidence of urethrostenosis, impotence
      and urinary incontinence in patients treated by cystostomy were significantly
      higher than rupture anastomosis on the stage I and early realignment (P < 0.05);
      while incidence in patients treated by catheterization was significantly lower
      than other groups (P < 0.05). CONCLUSION: For patients with partial rupture of
      posterior urethral, catheterization and rupture anastomosis on the stage I are
      preferred methods; while patients with complete rupture of posterior urethra,
      early realignment is a preferred method with advantages of simple operation and
      less complications.

PMID- 25058966
TI  - [Internal fixation for unstable scapular fracture].
AB  - OBJECTIVE: To investigate surgical methods and effects of unstable scapular
      fracture. METHODS: From October 2008 to August 2011, 14 patients with unstable
      scapular fracture were treated. There were 12 males and 2 females with an average
      age of 38.7 years (ranging, 21 to 55 years).The time from injury to
      hospitalization was 1 hour to 10 days (mean 3 days). Among patients,3 patients
      had scapular body fracture,4 patients had scapular neck and body fracture,4
      patients had scapular neck and acromion fracture,2 patients had glenoid cavity
      and coracoid fracture, 1 patient with scapular spine and coracoid fracture. All
      patients were treated by operation, Hardegger classification system was applied
      to evaluate the function. RESULTS: All patients were followed up for 2 to 36
      months (mean 12.4 months). The healing time ranged from 6 to 8 weeks. No
      infection and internal fixation failure occurred. The effect result of Hardegger
      scoring system was excellent in 9 cases, good in 3 cases, fair in 2 cases.
      CONCLUSION: Surgical treatment for unstable scapular fracture can reconstruct
      stability of shoulder joint, promote early rehabilitation of joint function, and
      maximally restore shoulder function.

PMID- 25058967
TI  - [Modified pinning combined with external tension band for the treatment of
      Gartland type III humeral supracondylar fractures in children].
AB  - OBJECTIVE: To explore therapeutic effects of Modified pinning combined with
      external tension band for the treatment of Gartland type III humeral
      supracondylar fractures in children. METHODS: From February 2009 to November
      2010, 79 children with Gartland type III humeral supracondylar fractures were
      treated by modified pinning (pinning cross internal and external condyle assisted
      with lateral condyle) combined with external tension band (crossing needle end
      and hooking around) through lateral approach of elbow. There were 47 males and 32
      females, with an average age of 8.7 years (ranging from 2.5 to 14 years). The
      time from injury to operation was 2 h to 8 d. The elbow joint function and
      Carrying angle were observed before and after treatment. The Flynn criteria were
      used to evaluate therapeutic effects. RESULTS: Sixty-one patients were followed
      up (18 patients' data were lost) for 6-30 months (mean 13.5 months). According to
      Flynn criteria, 53 patients got excellent result, 7 good and 1 fair. CONCLUSION:
      Treatment of child Gartland type III humeral supracondylar fractures with
      modified pinning combined with external tension band through lateral approach of
      elbow is believed to be an ideal method, which has advantages of reliable
      fixation, rapid recovery and less complications.

PMID- 25058968
TI  - [Diagnosis realization of knee joint synovial chondromatosis:clinical data of 28
      cases].
AB  - OBJECTIVE: To investigate diagnosis and therapeutic effects of knee joint
      synovial chondromatosis with arthroscopic. METHODS: From March 1995 to July 2011,
      28 patients with knee joint synovial chondromatosis were treated. Among them, 18
      males and 10 females ranging age from 25 to 81 (mean 55.2) years,the course of
      disease ranged from 0.5 to 15 (mean 5.6) years. Clinical manifestation mainly
      included pain, swell and functional limitation of knee joint. Knee open surgery
      (17 cases) and laparoscopic surgery (10 cases) were respectively used. Clinical
      symptom,image data,pathological manifestation and effects under arthroscopy were
      observed, Lysholm scoring was used to evaluate effects. RESULTS: All patients
      were followed up except one lost, the duration ranging from 6 to 24 months.
      Lysholm score in knee open surgery was increased from (41.89 +/- 6.81)
      preoperatively to (67.73 +/- 7.62) postoperatively;while in laparoscopic surgery
      it was increased from (40.78 +/- 7.54) preoperatively to (77.46 +/- 8.43)
      postoperatively. CONCLUSION: Arthroscopic surgery, which has no risk of rupture
      of incision, nonunion, earlier to exercise, is a good method to diagnosis and
      treat knee joint synovial chondromatosis.

PMID- 25058969
TI  - [Hippocrate method for the treatment of shoulder dislocation inducing by humerus
      anatomy neck fractures: 4 cases report].

PMID- 25058970
TI  - [Reasearch on mechanism of neurotrophins in discogenic low back pain].
AB  - Discogenic low back pain is the common type of chronic low back pain. However,its
      mechanism has not been completely clarified. Considerable evidence shows that
      neurotrophins play an important role in discogenic low back pain. The paper
      summarizes the mechanism of neurotrophins on discogenic low back pain according
      to the pain transfer pathway of neurotrophins in intervertebral disc, dorsal horn
      ganglia and spinal trigeminal nucleus. Changing the pain transmission by
      regulating neurotrophins and its receptor will provide a new way for the
      treatment of discogenic low back pain.

PMID- 25058971
TI  - [Preoperative analgesia in orthopaedic surgery].
AB  - Orthopaedic postoperative pain not only brings a lot of side effects to patients,
      but also directly affects early rehabilitation after surgery. Effective
      preoperative pain management mainly includes three-stage individual pattern
      analgesia, which refers to preoperative, intraoperative and postoperative
      analgesia. The purpose is to reduce pain in multiple planes and three-dimension,
      strengthen the effect of analgesics and reduce dosage and side effect of single
      drug. This paper summaries new progress on individual-multiple-pattern
      analgesics, pain assessment method and various therapies.

PMID- 25058972
TI  - Jumping off the readmissions carousel.

PMID- 25058973
TI  - The case for nurses' notes. Electronic medical records have many benefits, but it
      is imperative to maintain written documentation to clarify actual care.

PMID- 25058974
TI  - Feds revise key survey & cert provisions.

PMID- 25058975
TI  - Jettisoning rev limiters in the race toward fiscal health. What strategies,
      tactics boost revenue cycle management operations?

PMID- 25058976
TI  - Document management gets personal. Streamline your healthcare workflow.

PMID- 25058977
TI  - Bringing together PSOs and health IT. A perfect collaboration for quality patient
      care.

PMID- 25058978
TI  - An in-depth discussion on risk management.

PMID- 25058979
TI  - The role, and actual meaning, of analytics in healthcare.

PMID- 25058980
TI  - Three things healthcare CIOs should know about data warehouses.

PMID- 25058981
TI  - Nine key cyber threats identified in Verizon data breach report.

PMID- 25058982
TI  - Collaborating our way into interoperability.

PMID- 25058983
TI  - Grief, the inquisitor.

PMID- 25058984
TI  - Residential hospice environments: evidence-based architectural and landscape
      design considerations.
AB  - The residential hospice care movement is increasingly accepted and supported
      globally, and yet, unfortunately, the amount of literature on best practices in
      the planning and design of residential hospice facilities and adjacent outdoor
      spaces remains relatively small. This paper reports on a compendium of
      architectural and landscape design considerations that reflect the fundamental
      dimensions of the residential hospice experience: site and context, arrival
      spaces, communal and private spaces of the residential milieu, transitional
      spaces, and nature connectivity. Additionally, key staffing and administrative
      ramifications of this built-environment compendium are addressed, as are
      prognostications and challenges for the future.

PMID- 25058985
TI  - "Better pathways of care": suggested improvements to the emergency department
      management of people with advanced cancer.
AB  - OBJECTIVE: It is difficult to provide optimal care to people with advanced cancer
      presenting to emergency departments (EDs). Recent data suggest that the ED
      environment, the skills and priorities of treating staff, and the lack of clear
      communication related to goals of care contribute to the difficulty. By exploring
      the views of emergency, palliative care (PC), and oncology clinicians on the care
      of these patients, this study aimed to describe potential solutions. METHODS:
      This qualitative study involved focus groups with clinicians at two major
      hospitals and two community PC services in Melbourne, Australia, and
      semistructured telephone interviews with emergency clinicians from all other
      Australian states and territories. Discussions were recorded and transcribed
      verbatim. Thematic analysis identified ways to improve or enhance care. RESULTS:
      Throughout discussions with 94 clinicians, a number of possible improvements to
      care were raised; these were broadly grouped into service areas: clinical care,
      pathways, information access, and education. CONCLUSION: The provision of care to
      patients with advanced cancer in the ED occurs across sites, across disciplines,
      and across teams. To make improvements to care, we must address these
      complexities. The improvements suggested in this study place the patient (and the
      patient's family) at the centre of care.

PMID- 25058986
TI  - Distribution and sharing of palliative care costs in rural areas of Canada.
AB  - Few data are available on the costs occurring during the palliative phase of care
      and on the sharing of these costs in rural areas. This study aimed to evaluate
      the costs related to all resources used by rural palliative care patients and to
      examine how these costs were shared between the public healthcare system (PHCS),
      patients' families, and not-for-profit organizations (NFPOs). A prospective
      longitudinal study was undertaken of 82 palliative care patients and their main
      informal caregivers in rural areas of four Canadian provinces. Telephone
      interviews were completed at two-week intervals. The mean total cost per patient
      for a six-month participation in a palliative care program was CA$31,678 +/-
      1,160. A large part of this cost was attributable to inpatient hospital stays and
      was assumed by the PHCS. The patient's family contributed less than a quarter of
      the mean total cost per patient, and this was mainly attributable to caregiving
      time.

PMID- 25058987
TI  - Is performance status associated with symptom scores? A population-based
      longitudinal study among cancer outpatients.
AB  - BACKGROUND: Symptom scores and performance status are both important measures for
      patients with cancer. However, since performance status is not often part of
      routinely collected data, there is interest in exploring whether it can be
      calculated from symptom scores. METHODS: This was a population-based longitudinal
      study of cancer outpatients in Ontario, Canada in the year following their cancer
      diagnosis and among the subset of patients during the last year of their lives.
      RESULTS: In the first year after diagnosis, there was a significant relationship
      between performance status and fatigue and appetite; fatigue and well-being had a
      significant association with performance status in the last year of life. In both
      periods, the associations, although statistically significant, were not large
      enough to be clinically meaningful. CONCLUSION: Performance status is an
      important measurement that cannot be substituted or captured with symptom scores;
      it is important for healthcare providers to record performance scores on a
      regular basis.

PMID- 25058988
TI  - Experience of guilt and strategies for coping with guilt in patients with severe
      COPD: a qualitative interview study.
AB  - Guilt is associated with an increased level of mood disturbance and a poorer
      quality of life. The aim of this study was to explore how patients with severe
      COPD view and experience guilt and the ways in which they cope with this guilt. A
      total of 31 COPD patients were interviewed about their perceptions and
      experiences of guilt. Qualitative content analysis was used to examine the
      interviews. In the descriptive (manifest) analysis, the categories "not feeling
      personal guilt" and "experiencing guilt" emerged; in the interpretative (latent)
      analysis, various strategies for dealing with guilt were identified--for example,
      acceptance or blaming others. Relatively few patients reported that they felt
      guilt on a conscious level, but those who did expressed anguish, and remorse
      before God; some felt blamed by others. It is important that healthcare providers
      acknowledge the guilt that their patients express, since guilt may have adverse
      effects on the patients' overall health.

PMID- 25058990
TI  - Deathbed memories.

PMID- 25058989
TI  - Children's palliative care: considerations for a physical therapeutic
      environment.

PMID- 25058991
TI  - Comfortably numb.

PMID- 25058992
TI  - Does selective use of computed tomography scan reduce the rate of "white"
      (negative) appendectomy?
AB  - BACKGROUND: Appendectomies are the most common operations performed on an
      emergency basis. The accepted rate of "white" appendectomies is around 20%. In
      recent years, computed tomography (CT) scanning has been recognized as a valuable
      tool with high sensitivity and specificity in the diagnosis of acute
      appendicitis. The use of CT scans in the management of patients with suspected
      acute appendicitis is increasing worldwide. OBJECTIVES: To assess whether
      introducing more liberal use of CT in the management of patients presenting to
      the emergency room with right lower quadrant pain or suspected acute appendicitis
      would reduce the rate of "white" appendectomies. METHODS: We conducted a
      retrospective study of the pathology reports and CT scans of all patients who
      underwent appendectomy during a 3 year period. We examined the correlation
      between the rate of CT scans performed and the rate of "white" appendectomies.
      RESULTS: Overall, we performed 797 appendectomies during the study period. In
      2004, we performed 272 appendectomies and CT in 34 patients (12.5%). In 2005, we
      performed 275 appendectomies and CT in 83 patients (30.2%). In 2006, we performed
      250 appendectomies and CT in 88 patients (35.2%). The percentage of "white"
      appendectomies decreased from 29% in 2004 to 21.1% in 2005 and to 18.8% in 2006.
      CONCLUSIONS: It appears that a more selective use of CT scans in the management
      of suspected appendicitis could reduce the rate of "white" appendectomies.

PMID- 25058993
TI  - Complications following powered endoscopic sinus surgery: an 11 year study on
      1190 patients in a single institute in Israel.
AB  - BACKGROUND: Over the past 20 years, advances in endoscopic sinus surgery (ESS)
      techniques have led to widespread applications of this technology in both adult
      and pediatric populations with better results and lower morbidity. OBJECTIVES: To
      update data regarding the rate of minor and major complications following ESS
      procedures that used powered instrumentation. METHODS: We retrospectively
      reviewed the charts of all patients who, with general anesthesia, underwent ESS
      utilizing powered instrumentation between January 1996 and December 2006. Age,
      gender, indication for surgery, length of hospitalization, and type and rate of
      surgical complications were recorded. RESULTS: A total of 1190 patients were
      included in our study (1309 surgeries). The male:female ratio was 1.7:1.0 and the
      average age was 39 years (range 4-86 years). The most common indication for
      surgery was chronic rhinosinusitis. The rate of major complications was 0.31% and
      that of minor complications 1.37%. The only major complication that occurred was
      cerebrospinal fluid leak. The minor complications included epistaxis, periorbital
      emphysema, ecchymosis and mucocele formation. CONCLUSIONS: Compared to previously
      published series, the rate of major and minor complications in our study was low.
      The results indicate that the use of powered instruments during ESS is safe.

PMID- 25058994
TI  - Association of Helicobacter pylori with coronary artery disease and myocardial
      infarction assessed by myocardial perfusion imaging.
AB  - BACKGROUND: The relationship between Helicobacter pylori infection and coronary
      artery disease (CAD) has as yet not been fully examined. The myocardial perfusion
      imaging (MPI) stress test has proven its efficacy as an integral part of
      diagnosing CAD. OBJECTIVES: To investigate the association between CAD and H.
      pylori infection using MPI. METHODS: This prospective study evaluated CAD
      positivity among consecutive patients referred to a tertiary medical center for a
      stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA
      protein immunoglobulin G antibodies. The CAD positivity group included patients
      with ischemia and/or myocardial infarction (MA) on a stress MPI, coronary artery
      bypass graft surgery (CABG), or percutaneous coronary interventions (PCI). CAD
      negative subjects were defined as participants with a normal MPI, no pathological
      Q waves in resting ECG tracing, and no history of CAD. Both groups were compared
      for H. pylori and CagA seropositivity. Patients' demographic data, risk factors
      for CAD, and childhood socioeconomic status were recorded. RESULTS: The study
      group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173)
      CAD-positive patients and 47% (60/127) CAD-negative participants were found
      seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H.
      pylori infection was found to be associated with CAD positivity (odds ratio 1.83,
      95% confidence interval 1.06-3.17, P = 0.031), and MI (fixed perfusion defects on
      MPI) (OR 3.36, 95% CI 1.44-7.84, P = 0.005). No association was noted with CagA
      positivity. CONCLUSIONS: In patients undergoing a stress MPI, serum anti-H.
      pylori antibodies positivity was found to be associated with CAD, independent of
      traditional cardiovascular risk factors.

PMID- 25058995
TI  - Experience with sunitinib treatment for metastatic renal cell carcinoma in a
      large cohort of Israeli patients: outcome and associated factors.
AB  - BACKGROUND: The VEGFR/PDGFR inhibitor sunitinib was approved in Israel in 2008
      for the treatment of metastatic renal cell carcinoma (mRCC), based on an
      international trial. However, the efficacy of sunitinib treatment in Israeli mRCC
      patients has not been previously reported. OBJECTIVES: To report the outcome and
      associated factors of sunitinib treatment in a large cohort of Israeli mRCC
      patients. METHODS: We conducted a retrospective study of an unselected cohort of
      mRCC patients who were treated with sunitinib during the period 2006-2013 in six
      Israeli hospitals. Univariate and multivariate analyses were performed to
      determine the association between treatment outcome and clinicopathologic
      factors. RESULTS: We identified 145 patients; the median age was 65 years, 63%
      were male, 80% had a nephrectomy, and 28% had prior systemic treatment. Seventy
      nine percent (n = 115) had clinical benefit (complete response 5%, n = 7; partial
      response 33%, n = 48; stable disease 41%, n = 60); 21% (n = 30) were refractory
      to treatment. Median progression-free survival (PFS) was 12 months and median
      overall survival 21 months. Factors associated with clinical benefit were
      sunitinib-induced hypertension: [odds ratio (OR) 3.6, P = 0.042] and sunitinib
      dose reduction or treatment interruption (OR 2.4, P = 0.049). Factors associated
      with PFS were female gender [hazard ratio (HR) 2, P = 0.0041, pre-sunitinib
      treatment neutrophil-to-lymphocyte ratio < or = 3 (HR 2.19, P = 0.002), and
      active smoking (HR 0.19, P < 0.0001). Factors associated with overall survival
      were active smoking (HR 0.25, P < 0.0001) and sunitinib-induced hypertension (HR
      0.48, P = 0.005). To minimize toxicity, the dose was reduced or the treatment
      interrupted in 39% (n = 57). CONCLUSIONS: The efficacy of sunitinib treatment for
      mRCC among Israeli patients is similar to that in international data.

PMID- 25058996
TI  - Influence of the mode of management of acute myocardial infarction on the
      inducibility of ventricular tachyarrhythmias with programmed ventricular
      stimulation after myocardial infarction.
AB  - BACKGROUND: Programmed ventricular stimulation (PVS) is a technique for screening
      patients at risk for ventricular tachycardia (VT) after myocardial infarction
      (MI), but the results might be difficult to interpret. OBJECTIVES: To investigate
      the results of PVS after MI, according to date of completion. METHODS: PVS
      results were interpreted according to the mode of MI management in 801
      asymptomatic patients: 301 (group I) during the period 1982-1989, 315 (group II)
      during 1990-1999, and 185 (group III) during 2000-2010. The periods were chosen
      based on changes in MI management. Angiotensin-converting enzyme (ACE) inhibitors
      had been given since 1990; primary angioplasty was performed routinely since
      2000. The PVS protocol was the same throughout the whole study period. RESULTS:
      Group III was older (61 +/- 11 years) than groups I (56 +/- 11) and II (58 +/-
      11) (P < 0.002). Left ventricular ejection fraction (LVEF) was lower in group III
      (36.5 +/- 11%) than in groups I (44 +/- 15) and II (41 +/- 12) (P < 0.000).
      Monomorphic VT < 270 beats/min was induced as frequently in group III (28%) as in
      group II (22.5%) but more frequently than in group I (20%) (P < 0.03).
      Ventricular fibrillation and flutter (VF) was induced less frequently in group
      III (14%) than in groups I (28%) (P < 0.0004) and II (30%) (P < 0.0000). Low left
      ventricular ejection fraction (LVEF) and date of inclusion (before/after 2000)
      were predictors of VT or VF induction on multivariate analysis. CONCLUSIONS:
      Induction of non-specific arrhythmias (ventricular flutter and fibrillation) was
      less frequent than before 2000, despite the indication of PVS in patients with
      lower LVEF. This decrease could be due to the increased use of systematic primary
      angioplasty for MI since 2000.

PMID- 25058997
TI  - Interleukin-17 producing T cells could be a marker for patients with allergic
      rhinitis.
AB  - BACKGROUND: Interleukin-17A (I-17A)-producing CD4+T helper cells have been
      implicated in allergic inflammation; however, the role of IL-17A in allergic
      rhinitis (AR) patients with different degrees of atopy and airway reactivity to
      methacholine (Mch) has not been examined. OBJECTIVES: To explore IL-17A-producing
      CD3+CD4+T cells in peripheral blood of patients with persistent AR and assess the
      degree of atopy, eosinophil count (Eo count), and bronchial hyper-responsiveness
      (BHR) to methacholine. METHODS: The study involved 61 patients and 30 controls.
      The percentage of CD3+CD4+IL-17A+T cells in peripheral blood was measured by flow
      cytometry, bronchial challenges with Mch were performed, as were skin prick tests
      with standard inhalant allergens, and Eo count was measured. Atopic status was
      determined by the number of positive SPT results and wheal mean diameter.
      RESULTS: A statistically significant difference in Th17 cell percentage was found
      in the AR and control groups (2.59 +/- 1.32% and 1.24 +/- 0.22% respectively, P =
      0.001). Forty-one patients (67.2%) were polysensitized to indoor and outdoor
      allergens, while 20 (32.8%) had positive skin prick tests to indoor allergens.
      CD4+T cells were significantly higher in the patient group compared to the
      control group (2.91 +/- 1.5% versus 1.91 +/- 0.62%, P = 0.005), as was Eo count
      (4.48 +/- 2.13 vs. 2.32 +/- 1.83) (P = 0.0001). Forty-one in the AR group (67%)
      and 7 (23%) in the control group were Mch-positive (P = 0.001). The percentage of
      IL-17A-producing CD4+T cells was significantly higher in males compared to
      females (3.15 +/- 1.8% versus 2.31 +/- 0.9%, P = 0.02) CONCLUSIONS:
      Polysensitized AR patients exhibited higher IL-17A-producing CD4+T cell levels
      and eosinophil counts. Male patients displayed a higher frequency of IL-17A
      producing T cells.

PMID- 25058998
TI  - Advantages of minimal incision laparoscopic cholecystectomy.
AB  - BACKGROUND: Modifications to conventional laparoscopic cholecystectomy (CLC) are
      aimed at decreasing abdominal wall trauma and improving cosmetic outcome.
      Although single-incision laparoscopic surgery (SILS) provides excellent cosmetic
      results, the procedure is technically challenging and expensive compared to the
      conventional laparoscopic approach. OBJECTIVES: To describe a novel, hybrid
      technique combining SILS and conventional laparoscopy using minimal abdominal
      wall incisions. METHODS: Fifty patients diagnosed with symptomatic cholelithiasis
      were operated using two reusable 5 mm trocars inserted through a single 15 mm
      umbilical incision and a single 2-3 mm epigastric port. This technique was
      clubbed "minimal incision laparoscopic cholecystectomy" (MILC). RESULTS: MILC was
      completed in 49 patients (98%). In five patients an additional 3 mm trocar was
      used and in 2 patients the epigastric trocar was switched to a 5 mmtrocar. The
      procedure was converted to CLC in one patient. Mean operative time was 29 minutes
      (range 18-60) and the average postoperative hospital stay was 22 hours (range 6
      50). There were no postoperative complications and the cosmetic results were
      rated excellent by the patients. CONCLUSIONS: MILC is an intuitive, easy-to-learn
      and reproducible technique and requires small changes from CLC. As such, MILC may
      be an attractive alternative, avoiding the cost and complexity drawbacks
      associated with SILS.

PMID- 25058999
TI  - Association between vitamin D levels and alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is an autoimmune disease, based on the response
      to local and/or systemic corticosteroid treatment. The role of vitamin D in the
      pathogenesis of immune/autoimmune mediated diseases has been widely studied.
      OBJECTIVES: To investigate a possible association between serum 25-hydroxyvitamin
      D levels and alopecia areata. METHODS: The study included 23 patients diagnosed
      with AA followed at our outpatient clinic during the period March 2010 to May
      2011, as well as a control group matched for age and gender. All subjects
      underwent a complete work-up and medical examination, anthropometric measurements
      and laboratory tests. Laboratory tests included complete blood count, C-reactive
      protein (CRP), and vitamin D levels. RESULTS: Mean CRP values were significantly
      higher in the AA group than the control group (1.1 +/- 0.7 mg/dl vs. 0.4 +/- 0.8
      mg/ dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group
      (11.32 +/- 10.18 ng/ml vs. 21.55 +/- 13.62 ng/ml in the control group, P < 0.05).
      Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval
      2.6-4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95% CI 2.2-3.1,
      P = 0.02) were associated with AA. CONCLUSIONS: We found a significant
      correlation between AA and vitamin D deficiency. Vitamin D deficiency can be a
      significant risk factor for AA occurrence.

PMID- 25059000
TI  - Perinatal outcome and financial impact of Eritrean and Sudanese refugees
      delivered in a tertiary hospital in Tel Aviv, Israel.
AB  - BACKGROUND: A growing number of Eritrean and Sudanese refugees seek medical
      assistance in the labor and delivery ward of our facility. Providing treatment to
      this unique population is challenging since communication is limited and
      pregnancy follow-up is usually absent. OBJECTIVES: To compare the perinatal
      outcome of refugees and Israeli parturients. METHODS: The medical and financial
      records of all refugees delivered between May 2010 and April 2011 were reviewed.
      Perinatal outcome was compared to that of native Israeli controls. RESULTS:
      During this period 254 refugees were delivered (2.3% of deliveries). Refugees
      were significantly younger and leaner. They had significantly more premature
      deliveries under 37 weeks (23 vs. 10, P = 0.029) and under 34 weeks gestation (9
      vs. 2, P = 0.036) with more admissions to the neonatal intensive care unit (15
      vs. 5, P = 0.038). Overall cesarean section rate was similar but refugees
      required significantly more urgent surgeries (97% vs. 53%, P = 0.0001). Refugees
      had significantly more cases of meconium and episiotomies but fewer cases of
      epidural analgesia. There were 2 intrauterine fetal deaths among refugees,
      compared to 13 of 11,239 deliveries during this time period (P = 0.036), as well
      as 7 pregnancy terminations following sexual assault during their escape. Sixty
      eight percent of refugees had medical fees outstanding with a total debt of
      2,656,000 shekels (US$ 767,250). CONCLUSIONS: The phenomenon of African refugees
      giving birth in our center is of unprecedented magnitude and bears significant
      medical and ethical implications. Refugees proved susceptible to adverse
      perinatal outcomes compared to their Israeli counterparts. Setting a pregnancy
      follow-up plan could, in the long run, prevent adverse outcomes and reduce costs
      involved in treating this population.

PMID- 25059001
TI  - Arrhythmogenic right ventricular cardiomyopathy.

PMID- 25059002
TI  - No(AC) free lunches: promises and pitfalls of novel oral anticoagulants.

PMID- 25059003
TI  - Interventional pulmonology: a new medical specialty.
AB  - Interventional pulmonology (IP) is the newest chapter in respiratory medicine. IP
      includes both diagnostic and therapeutic methods. Nanotechnology, in both
      instrumental engineering and optical imaging, will further advance this
      competitive discipline towards cell diagnosis and therapy as part of the future's
      personalized medicine.

PMID- 25059004
TI  - Arrhythmogenic right ventricular cardiomyopathy: an unusual possible cause of
      arrhythmia in a 78 year old man with a 40 year history of palpitations.

PMID- 25059005
TI  - Dabigatran etexilate linked to fatal gastrointestinal hemorrhage.

PMID- 25059006
TI  - Membranous nephropathy associated with sarcoidosis: a primary or secondary
      glomerulopathy?

PMID- 25059007
TI  - Radiologic features of acne fulminans.

PMID- 25059008
TI  - Neonatal adrenal hemorrhage presenting as Bryant's and Stabler's signs.

PMID- 25059009
TI  - Celiac disease in an Ethiopian Jew.

PMID- 25059010
TI  - Werner syndrome: clinical evaluation of two cases and a novel mutation.
AB  - Werner syndrome (WS) is a premature aging disorder, inherited in an autosomal
      recessive pattern and caused by the mutation in the WRN gene. In this report we
      describe two male patients with negative family history who demonstrate
      characteristic findings of WS, with different mutations, including one novel
      mutation. The first case was a 47-year-old man who had been suffering from large,
      ischemic ulcers on both legs for 7 years. Physical examination revealed a thin
      and short man with severe wasting of all extremities. He had a high-pitched
      voice, hoarseness, a characteristic bird-like facies, bilateral cataracts,
      generalized osteoporosis, hypotrichosis, atrophic and poikilodermic skin, flexion
      contractures of hands, feet and knees, and soft tissue calcifications. Laboratory
      investigations revealed anemia, high erythrocyte sedimentation rate, low
      creatinine clearance, and high liver enzymes. Genetic analysis showed a
      homozygous novel 1bp-deletion in exon 19 of WRN, 2426/27delG, causing frameshift
      and protein truncation R809SfsX2, which has not been described before. The second
      case was a 23-year-old man who was referred for large callosities on both feet,
      present for 7 years. He complained of weakness, weight loss, wasting of muscles,
      and early graying of hair. The entire skin was thin, wrinkled and dry.
      Generalized hypotrichosis, scattered ephelid-like macules, sclerotic fingers,
      calcinosis cutis on ears, hyperpigmentation on elbows were the other alterations
      of skin. Skeletal survey revealed osteoporosis. Genetic analysis showed a
      homozygous known pathogenic splice site mutation c.3460-2A>G, causing skipping of
      Exon 30 in WRN.

PMID- 25059011
TI  - Duchenne muscular dystrophy in a developing country: challenges in management and
      genetic counseling.
AB  - BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular
      Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed
      to describe the status of diagnosis and management of DMD in a developing country
      through the experience of non-profit organizations. METHODS: A Multistate,
      multiple-source, population-based survey was performed from medical records of
      432 patients. Data were retrospectively collected, reviewed and curated by health
      specialists; including clinical features, age at first symptoms, age at
      diagnosis, disease progression and management, family history, education, age and
      cause of death. RESULTS: There is a delay in noticing first symptoms and it did
      not diminish over the past 20 years. Less than 30% of patients obtained definite
      diagnosis and most of them are in physiotherapy programs but not under steroid
      treatment. In our study, family history does not anticipate recognition of
      symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our
      patients attended to education programs. Mean age at death was 18.94 +/- 6.73
      years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of
      DMD in Mexico is mainly caused by the late detection of first symptoms. There is
      no difference in early detection of symptoms between familiar and sporadic cases.
      Lifespan of patients in our cohort is reduced compared to developed countries.
      The late diagnosis and low percentage of definite cases may affect patient
      management and genetic counseling and could also preclude participation of
      patients into novel clinical trials.

PMID- 25059012
TI  - Genetic risk score for nonsyndromic cleft lip with or without cleft palate for a
      Chilean population.
AB  - It has been widely accepted that nonsyndromic cleft lip with or without cleft
      palate (NSCLP) depends on the altered function of several genes during
      craniofacial development. The construction of genetic risk score (GRS) have
      allowed to estimate the combined effect of risk alleles from genes interacting in
      different molecular pathways in order to improve an estimation of the
      individual's susceptibility to a complex disease. The aim of our study was to
      construct a GRS considering markers showing previous allele/haplotype association
      with NSCLP in Chile. Considering 10 risk markers from IRF6, MSX1, BMP4 and TGFB3
      genes, we estimate a GRS for each of 152 NSCLP cases and 164 controls. GRS showed
      no significant results when comparing cases and controls for these markers. These
      results could be explained by a possible indirect relationship of these genes
      between them in NSCLP which GRS is not capable of detecting and/or the modest
      number of risk alleles considered herein.

PMID- 25059013
TI  - Terminal 2q deletion and partial trisomy chromosome 15q: a clinical and
      cytogenetic study.
AB  - We report on a 5 years old female patient with a karyotype 46, XX, add (2),
      t(2;15) (q37;q22) associated with dysmorphic facial features, digital
      deformities, heart defect (mild mitral regurge) and severe mental retardation.
      This is the third reported case worldwide on the terminal 2q deletion and trisomy
      of chromosome 15q syndrome. The findings in this case and our literature review,
      delineates the pattern of malformations secondary to trisomy of 15q and deletion
      of 2q.

PMID- 25059014
TI  - Syndromes presenting adducted thumb with/without clubfoot and Dundar syndrome.
AB  - Congenital adducted thumb has been called variously as congenital clasped thumb,
      thumb in palm deformity or flexion adduction deformity of the thumb. This
      condition can be an isolated anomaly or associated with several genetic
      disorders. The syndromes that include adducted thumb as a cardinal feature such
      as Dundar Syndrome are few in the literature. This syndrome is an autosomal
      recessive very rare disorder characterized by typical facial appearance with
      dysmorphic features that includes wasted build, hyperextensible, thin and
      translucent skin with atrophic scarring, severe congenital contractures of
      fingers and thumbs, club feet, severe kyphoscoliosis, joint instability, muscular
      hypotonia, and ocular involvement. Heart, kidney, and/or intestinal defects can
      also be observed. Up to date the syndrome is described in few families in the
      literature. Here we discuss the syndromes that include adducted thumb as a
      cardinal feature and also the differential diagnosis of the Dundar Syndrome
      according to the literature.

PMID- 25059015
TI  - A case of Seckel syndrome with tricuspid atresia.
AB  - Seckel syndrome is an autosomal recessive disease presenting with marked growth
      retardation, microcephalic dwarfism, some facial and skeletal abnormalities.
      Tricuspid atresia is a rare and life threatening cyanotic congenital heart
      diseases, with an incidence of 1% to 3%. It is feature of the anatomically
      normally related great arteries with a large ventricular septum defect and
      stenosis of right ventricular outflow tract. Tricuspid atresia has never been
      reported in patients with Seckel syndrome. Here we report a 15-day-old girl baby
      diagnosed as having Seckel syndrome with tricuspid atresia.

PMID- 25059016
TI  - Mosaic double aneuploidy (45,X/47,XX,+8) with aortic dissection.
AB  - Chromosomal aneuploidy is considerably frequent and may involve either autosomes
      or sex chromosomes. While double aneuploidy involving both autosomal and sex
      chromosomes is rare, several reports described the cases of sex chromosomal
      aneuploidies in combination with trisomy 21, such as Down-Klinefelter and Down
      Turner syndrome. However, trisomy 8-Turner syndrome has been rarely described to
      date. Here we report a case of a 28-year-old female with mosaic trisomy 8-Turner
      syndrome. The patient was referred to our hospital for aortic dissection. On
      physical evaluation, features of her phenotype, which included short stature,
      webbed neck and cubitus valgus, suggested congenital anomalies such as Turner
      syndrome. Chest CT revealed aortic dissection with bicuspid aortic valve and
      coarctation. G-banding cytogenetic analysis of peripheral blood showed mosaicism
      with two cell lines (45,X[17]/47,XX,+8[33]). FISH analysis indicated that 15% of
      the cells were of monosomy X karyotype and 85% of the cells were with XX
      karyotype and trisomy 8 was detected only in XX cells. Though the patient
      exhibited clinical features of Turner syndrome, somatic stigmas present were not
      clearly distinguishable from those of trisomy 8, such as short stature, skeletal
      and cardiac abnormalities. Observations from most of the double aneuploidy cases
      indicated that the patient's phenotype was not necessarily in correlation to the
      ratio of autosomal and sex chromosomal aberrations. Mosaicism in trisomy 8-Turner
      syndrome was rarely documented and we believe this is the first reported case of
      mosaicism in trisomy 8-Turner syndrome presenting with aortic dissection and
      surviving into adulthood.

PMID- 25059017
TI  - Precocious puberty in a patient with mosaic Turner syndrome.
AB  - Turner syndrome (TS) is one of the most common human chromosome abnormalities,
      occurring in approximately 1:2500 live female births. Short stature, ovarian
      dysgenesis and infertility are clinical hallmarks in the majority of patients
      with TS. The incidence of spontaneous puberty in TS is reported to be about one
      third. Precocious puberty in TS patients is very rare. Herein, we report
      precocious puberty in a case with TS.

PMID- 25059018
TI  - Left cerebral hemisphere and ventricular system abnormalities in a Mexican Meier
      Gorlin syndrome patient: widening the clinical spectrum.
AB  - The Meier-Gorlin syndrome (MGS) or ear, patella, short stature syndrome (MIM
      #224690) is a rare disorder with bilateral microtia, aplasia or hypoplasia of the
      patellae and severe intra-uterine and post-natal growth retardation. We report
      the case of a 10-year-old male with MGS diagnosis, his parents were related, he
      also showed conductive hearing loss and maloclussion and long upper central
      incisors, more importantly he had asymmetry of the left cerebral hemisphere and
      ventricular system, his intelligence was normal. As far as we know, these
      abnormalities have not been previously described in patients with MGS and the
      present report corresponds to the first Mexican case described so far.

PMID- 25059019
TI  - De novo interstitial deletion of 9q32-34.1 with mental retardation, developmental
      delay, epilepsy, and cortical dysplasia: a case report.
AB  - In this report we describe a 10 year-old female patient with interstitial
      deletion of 9q32-q34.1 associated with mental retardation, developmental delay,
      short stature, mild facial dysmorphism, epilepsy, abnormal EEG and brain MRI
      findings consistent with focal cortical dysplasia. Interstitial deletion of 9q
      associated with q32-q34 is found extremely rare. Common features of seven
      previously reported cases are mental retardation, developmental delay, short
      stature, a distinct cranial and facial phenotype (brachycephaly, low midface, low
      and prominent forehead, and low set malformed ears). Combination of epilepsy,
      abnormal EEG and brain MRI findings are not reported before.

PMID- 25059020
TI  - A vestibular schwannoma in a patient with Birt-Hogg-Dube syndrome.
AB  - Birt-Hogg Dube syndrome is an autosomal dominant disease with variable clinical
      expression. It is characterized by cutaneous manifestations, renal tumors and
      lung cysts. Other tumors, such as adrenal tumors and tumors originating from the
      neural crest cells such as meningioma and neurothekeoma have also been described.
      This syndrome is caused by germline mutations in the folliculin (FLCN) gene
      located on chromosome 17p. We report, for the first time, a patient with BHDS and
      a history of a vestibular schwannoma in adolescence. The diagnosis of BHDS was
      confirmed, by identifying a nonsense mutation in exon 10 of the FLCN gene. A
      vestibular schwannoma also originates from neural crest cells, just as other
      neural tumors, previously encountered in patients with BHDS. The reported
      mutations cause a truncation of the protein, folliculin. The exact role of
      folliculin is still undetermined. Two different theories suggest the effect of
      tumorigenesis. One is that folliculin plays an important role in the AMPK-mTOR
      pathway which leads to proliferation of cells when activated. The other is that
      the folliculin acts as a possible tumor suppressor gene, since there is a high
      frequency of second hits in the FLCN-gene. In order to confirm a possible
      relation of BHDS and neural crest tumors, further research is necessary in the
      tumorigenesis of the folliculin gene.

PMID- 25059021
TI  - Isolated ectrodactyly in a newborn with Down syndrome.
AB  - Down syndrome (DS), trisomy 21, is the most common numerical chromosome
      abnormality among live born infants. Dysmorphic features, congenital
      malformations, cognitive impairment are major features. Musculoskeletal anomalies
      are associated with abnormal collagen function. Ectrodactyly is characterized by
      a deep median cleft of the hand and/or foot. Failure of apical ectodermal ridge
      while developing limbs leads to ectrodactyly. Here we report a patient diagnosed
      with DS and ectrodactyly which were split between the third and fourth fingers
      and there were 4 fingers on both hands. There was no additional musculoskeletal
      anomaly. Karyotype analysis revealed 47,XY,+21. To the best of our knowledge our
      patient is the first patient with DS and ectrodactyly. Pathogenesis
      ofmusculoskeletal anomalies in DS and ectrodactyly seems to be different which
      may be coincidental or not. In conclusion, patients with ectrodactyly should be
      evaluated for association with syndromes, and it should be kept in mind that
      patients with Down syndrome may have different organ anomaly from frequently seen
      anomalies.

PMID- 25059022
TI  - A case report of rare XXY/XX mosaicism in a phenotypic male with Klinefelter
      syndrome and mediastinal germ cell tumor.
AB  - Klinefelter syndrome (KS) is a common sex chromosome disorder and is
      characterized by small, firm testes with hyalinization of the seminiferous
      tubules, elevated gonadotropins and azoospermia. Among karyotypic variants of KS,
      mosaicism 47,XXY/46,XX is extremely rare. We report here a case of an 18-year-old
      boy with a mosaic 47,XXY/46,XX karyotype of peripheral blood diagnosed as KS. The
      boy presented with anterior mediastinal mass which was confirmed as combined
      carvenous lymphangioma and mixed germ cell tumor by histologic examination of
      resected tissue. He had the male phenotype, however, azoospermia was incidentally
      detected on sperm banking analysis, performed prior to chemotherapy for mixed
      germ cell tumor. He had small and firm testes, mild gynecomastia, collectively
      tanner stage IV, mild hypergonadotropic hypogonadism and no evidence of true
      hermaphroditism. This report presents a rare case of mosaicism 47,XXY/46,XX
      karyotype in a phenotypic male with KS and mediastinal germ cell tumors. Based on
      what we experienced and review of the literature, cytogenetic analysis is
      recommended when physicians are confronted with a young patient with mediastinal
      germ cell tumor.

PMID- 25059023
TI  - Genome-wide copy number variation analysis in idiopathic intellectual
      disability/multiple congenital anomalies.
AB  - New array technologies have facilitated the analysis of submicroscopic
      chromosomal imbalances and structural variants. Copy number variation (CNV)
      analysis can reveal genetic imbalances in up to 10% of cases involving
      intellectual disability (ID), with or without multiple congenital anomalies
      (MCA). Here we present 4 cases, diagnosed by CNV analysis using Affymetrix Genome
      Wide Human SNP 6.0 array, and their parents. CNVs ranging from 18 to 196 per
      subject, with a size range of 100kb- 6093kb, were detected in all cases. One case
      revealed inherited CNVs, whilst de novo ins/dels were found in the other three
      which may be causative factors in the development of clinical pictures.
      Microarray technology may help to reveal the etiology of ID and is a potentially
      useful diagnostic tool for patients with ID/MCA.

PMID- 25059024
TI  - VACTERL association with a rare vertebral anomaly (butterfly vertebra) in a case
      of monochorionic twin.
AB  - The VATER/VACTERL association is typically defined by the presence of at least
      three of the following congenital malformations: vertebral anomalies, anal
      atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and
      limb abnormalities (13). We report a rare case of a monochorionic twin gestation
      in which one of the infants had VACTERL association. Antenatal ultrasound showed
      bilateral renal dysplasia and cardiac anomaly (ASD) in twin A. Twin A was noted
      to have the following anomalies: a single umbilical artery, limb anomaly (right
      hand preaxial polydactyly), vertebral anomalies (T9 and T11 butterfly vertebras,
      bilateral renal agenesis, bladder agenesis, anal and urethral atresia. A normal
      sized stomach and normal amount of amniotic fluid were observed during the
      prenatal period with no other anomalies. Twin B (male) was healthy and no
      cardiac, renal, or congenital anomalies were demonstrated on ultrasound and
      physical examination. Infant A was also diagnosed as having VACTERL association
      because he had five of the core anomalies (V, A, C, R, L) of VACTERL association.
      Butterfly vertebra is an uncommon congenital spinal anomaly. To the best of our
      knowledge, our patient is the second case VACTERL association with butterfly
      vertebra in the literature.

PMID- 25059025
TI  - Craniorachischisis, gastroschisis, and a branchial sinus defect: a case report.

PMID- 25059026
TI  - An interesting coexistence of Patau syndrome; Spigelian hernia and undescended
      testes.

PMID- 25059027
TI  - Lower extremity amputation in a preterm infant due to MTHFR homozygosity.

PMID- 25059028
TI  - [The role of occupational physician in the risk assessment].
AB  - Occupational Physician has a marginal role in the Risk Assessment (RA). He is
      rarely involved and generally he only reads the documentation of RA made by other
      specialists in the prevention and safety. The law obliges him to work with the
      Employer, not only for the planning of health surveillance but also for the
      preparation of measures for the protection of the health and psycho-physical
      integrity of workers. But it is mainly for the content and methodology of the RA
      that it is necessary the contribution of the occupational physician. The RA is in
      fact a multi-stage and multi-disciplinary activity carried out in close
      collaboration with industrial hygienists, ergonomists, safety experts,
      psychologists. The occupational physician for his studies and education is the
      most appropriate professional to evaluate the quality of the data and to make an
      integration between indicators of environmental contamination and biological
      indicators of internal dose and effect or damage. We agree with the Italian
      Society of Occupational Health and Industrial Hygiene that is necessary to
      proceed to the recognition of the role of occupational physician as a
      "consultant" of the company about health and safety in the workplace and involved
      in RA even when it is not necessary the health surveillance.

PMID- 25059029
TI  - [Primary headache and work: concepts of pathophysiology, occupational risk
      factors, health monitoring and criteria for judging causation].
AB  - Primary headaches account for 90% of all the forms of headache. The disease is
      characterized by high occurrence in the working-age population and by significant
      impact in countries with high economic and social development. These two
      epidemiological aspects carry significant economic costs that can be estimated
      calculating loss of working days due to illness and appreciable loss of labour
      productivity. In an occupational setting several circumstances are known to cause
      the onset of attacks in workers who already suffer from primary headache. In this
      sense, the following factors have an important role: interruption of the
      circadian sleep-wake rhythm, sleep deprivation, physical/mental distress, not
      ergonomic postures (mainly those involving the cervical-brachial district),
      prolonged use of display screen, acoustic discomfort. Among chemicals, in the
      current conditions of exposure, the olfactory characteristics seem of primary
      importance rather than the more "conventional" mechanism of toxicity. The main
      aim of this study is to provide useful information to occupational physicians on
      the management of workers suffering from primary headache, with regard either to
      the formulation of the judgement of suitability, or to their auxiliary role in
      the planning and organization of work. A second aim involves the identification
      of specific preventive measures in order to reduce the probability of occurrence
      of a headache attack. This also minimizes the risk of accidents and injuries and
      ensures workers' efficiency. After these considerations, we suggest guidelines
      for a flow chart (aimed to understand worker's suitability for his/her specific
      task). This guarantees not only safety and health of workers who suffer from the
      illness, but also safeguards any third worker from a possible consequence due to
      less working capacity and reduction of attention of employees working with a
      headache attack. In conclusion we also identify three critical factors: the
      diagnosis of the form of primary headache, the characteristics of the work and
      the effects due to pharmacological therapy. The study and characterization of
      these elements are a crucial step for a proper formulation of the judgement of
      suitability to work. We report a decision process for judgement formulation at
      the end of this article. It is organized with a hierarchical model, the first
      steps are the clinical examination and history, the last step, if necessary or
      advisable, is the neurological visit and a periodic verification of the adherence
      to treatment prescribed and the follow-up.

PMID- 25059030
TI  - [Emotional well-being and discomfort at work in call center].
AB  - INTRODUCTION: The theme of well-being and discomfort at work has attracted
      increasing interest in recent years. The present study, according to Job Demands
      Resources model (JD-R), inquires the effects of personal (optimism, internal
      locus of control) and organizational resources (job autonomy, supervisors and
      colleagues support) and general (work-to-family conflict, workload) and context
      specific demands (emotional dissonance) on emotional well-being and discomfort at
      work in call centre employees. METHODS: This research was conducted through an
      online questionnaire, composed by measures present in scientific literature,
      filled out individually by call center agents (N = 507) of the same
      telecommunication firm. Data analysis (PASW 18) provides: descriptive statistics,
      correlations and multiple regressions. RESULTS: Personal and organizational
      resources improve emotional well-being at work, except for colleagues support.
      Optimism and supervisors support reduce emotional discomfort at work. Among
      organizational demands, work-family conflict and emotional dissonance increase
      emotional discomfort at work and, to a lesser extent, reduce the emotional well
      being at work. CONCLUSIONS: The results, according to theoretical model,
      highlight the different role of demands and resources on emotional well-being and
      discomfort at work. The results suggest organizational politics and investments
      to promote emotional well-being at work, in particular training program to
      support emotional skills, training for supervisors, increasing job autonomy and
      support to work-family balance.

PMID- 25059031
TI  - [Female breast cancer and occupational sectors: a preliminary study in the
      provinces of Lombardy, Italy].
AB  - BACKGROUND: The role of occupational exposures in breast cancer development is
      still uncertain. A recent paper showed increased risks in some occupational
      sectors in Lombardy, Italy. We deepened this analysis at the level of single
      provinces of the same Italian region. METHODS: Based on administrative data, a
      case-control study was carried out recruiting all incident cases of female breast
      cancer in the period 2002-2009, aged between 35 and 69 years, residing in
      Lombardy, Italy. Controls were randomly sampled from all women residing in
      Lombardy as of December 31, 2005. Occupational histories, including blue collar
      status, were available from 1974 through record linkage with a social security
      pension database, and were obtained for 11188 cases and 25329 controls. Adjusted
      odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were
      calculated using multiple unconditional logistic regression models. Analyses were
      performed also by single provinces of Lombardy, Italy. Multiple comparisons were
      accounted for according to the Benjamini-Hochberg method. RESULTS: The ORs for
      female breast cancer were modestly but significantly increased for employment in
      electrical manufacturing (OR 1.12, 90% CI 1.04-121), textile (OR 1.08, 90% CI
      1.02-1.15), paper (OR 1.25, 90% CI 1.06-1.46) and rubber (OR 1.26, 90% CI 1.03
      1.54) industries. Analysis by province showed significantly increased ORs for
      electrical manufacturing in the Milano province. After adjustment for multiple
      comparisons no estimates remained statistically significant, except OR for
      electrical manufacturing in the Milano province. CONCLUSIONS: Although with
      several limitations, our results point to a possible role of exposures in
      electrical manufacturing, textile, paper and rubber industries in the process
      leading to breast cancer. An in-dept study for the electrical manufacturing
      industry has been already planned in Milano province.

PMID- 25059032
TI  - Occupational brain cancer risks in Umbria (Italy), with a particular focus on
      steel foundry workers.
AB  - OBJECTIVES: As a part of the Occupational Cancer Monitoring (OCCAM) project, a
      routine analysis based on Umbria region cancer registry (RTUP) database in 2002
      2008 was performed. Among other results, the incidental finding of brain cancer
      increased risk in steel foundry workers in Terni province (Italy), lead us to
      deepen the analysis, focusing on this specific industrial sector. METHODS: A
      monitoring study, based on Umbria Regional Cancer Registry data, was recently
      carried out. Brain cancer cases and controls identified within this preliminary
      study were selected. Therefore, we considered all incident cases (in Umbria
      region 2002-2008) of brain cancer occurred among workers occupied for at least
      one year in private companies since 1974 and controls randomly sampled from the
      same population. Afterwards, taking in to account results from steel foundry in
      Terni province, we further deepened our analysis, focusing on this productive
      sector. Odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were
      calculated using multiple logistic regression models, adjusted by age at
      diagnosis or sampling, sex and province of residence, when appropriate. RESULTS:
      Statistical analyses were carried out on 14913 subjects, 56 cases and 14857
      controls. Significantly increased ORs were observed for garment, mechanical
      manufacturing and chemical industries. Moreover, the risk estimates were strongly
      correlated with exposures in iron and steel foundries and a cluster of 14 cases
      in the same foundry in Terni was observed (OR 9.59, 90% CI 2.76-33.34).
      CONCLUSIONS: Results of this explorative study showed increased ORs of brain
      cancer in some productive branches, involving possible exposures to chemical
      compounds and/or solvents. Moreover, our results pointed out a significantly
      increased risk in Terni foundry workers, determining an interesting brain cancer
      cluster (14 cases). Further studies on this industrial sector are needed with
      improved definitions of tasks and exposures.

PMID- 25059033
TI  - [Reactive anxiety crisis and chronic adjustment disorder: a unique case of work
      injury and suspected occupational disease].
AB  - The present study aims to describe a case of work injury and occupational disease
      which is unique for the type of disease diagnosed, conditions of onset and mode
      of management by INAIL (Italian National Institute of Insurance for Injuries at
      Work and Occupational Diseases). A worker, after a verbal animated dispute with
      some collegues and superiors, had an acute psychiatric agitation attack and went
      to the nearest emergency room, where he was subjected to clinical exams. No
      neuropsychiatric alteration was found, but the physicians diagnosed an anxiety
      crisis reactive to the work environment. Consequently, the medical certificate
      for work injury was edited and sent to INAIL. The worker has been off work for
      110 days because of a anxious and depressive syndrome, due to the verbal
      conflict. In a later assessment, INAIL recognized only the first 30 days of the
      employee's time off as injury at work, while judging the following period off
      work as related to affectivity disturbance due to common disease, not related to
      work environment. The following year, "anxious-depressive syndrome" is worsened
      and attributed by the same worker to the recurrence of acts of persecution and
      discrimination against him at work. For this reason he applied for recognition of
      occupational disease diagnosed as "Chronic Adjustment Disorder with prolonged
      depressive reaction and somatic anxiety, which developed into a protracted
      conflict marked the employment situation". INAIL rejected that request, but in
      the same year the employee has submitted the complaint for "mobbing". Even this
      request was rejected. Literature shows many examples of traumatic events during
      working activities which cause psychiatric disturbances. These events include
      industrial disasters, explosions, transport and mining accidents, accidents in
      psychiatric units with high risks of assaults, armed conflicts, war, assault and
      sexual assault, natural disasters. Victims show symptoms of acute stress disorder
      (ASD) or post-traumatic stress disorder (PTSD). Cases of acute stress disorder
      resulting only from verbal conflict recognised as work injury aren't currently
      described. This case opens new perspective for the occupational physician in the
      assessment of ASD as work injury and of PTSD as professional disease, suggesting
      to put more attention to psychiatric health of workers.

PMID- 25059034
TI  - [Using the Mini-Mental State Examination (MMSE) for preliminary assessment of
      cognitive impairment in subjects exposed to air pollution with particulate
      matter].
AB  - Epidemiologic and clinical studies have linked elevated concentrations of
      particulate matter to adverse health effects. In particular, has been
      demonstrated an association between UFPs exposure and occurrence of acute
      respiratory infections, lung cancer, chronic chronic obstructive pulmonary
      diseases and cardiovascular diseases. Recently, the exposure to particulate air
      pollution has been linked to cognitive decline. In this work, we used the Mini
      Mental State Examination (MMSE) in a preliminary assessment of cognitive function
      in individuals who have lived and carried out work in heavily urbanized areas,
      where ambient levels of particulate air pollution were frequently above the
      standard of the law. The results showed the presence of mild-moderate cognitive
      impairment in 39.4% of the subjects examined compared to the control group.

PMID- 25059035
TI  - Abnormal lipid metabolism in collagen-induced arthritis rat model: in vitro, high
      resolution NMR spectroscopy based analysis.
AB  - Collagen-induced arthritis (CIA) was induced in female Wistar rats by intradermal
      injection of porcine immunization grade native collagen type II (Chondrex).
      Development and progression of CIA was monitored by studying histopathological,
      radiographical and biochemical features of arthritic manifestations in the knee
      joints, hind limb and blood plasma. In addition, oxidative stress status of
      arthritic animals was determined by measuring lipid peroxidation and the
      antioxidant enzymes: catalase, superoxide dismutase and glutathione peroxidase.
      High resolution proton NMR spectroscopy was employed for the analysis of lipid
      components in the lipid extracts of the joint tissue and plasma of collagen
      induced arthritic and control rats. Triglyceride levels showed significant
      decreases in plasma (1.7 times) but were unchanged in the joint tissue of CIA
      rats as compared to control. One-dimensional proton NMR spectra showed a 6.2
      times reduction in the quantity of choline-containing phospholipids in the plasma
      of CIA as compared to control rats. There was a 1.6 times elevation of choline
      containing phospholipids in the joint tissue of CIA rats as compared to controls.
      Induction of arthritis showed a 4.0 times reduction in the level of total
      cholesterol in the plasma and 1.6 times elevation in the joint tissue of CIA rats
      as compared to controls. The ratio of saturated fatty acids to unsaturated fatty
      acids was 1.5 times significantly higher in joint tissue and 2.1 times
      significantly higher in plasma of CIA rats as compared to controls. The results
      demonstrated significantly altered lipid patterns in the joint tissue and plasma
      of collagen-induced arthritic rats as detected by one- and two-dimensional NMR
      spectroscopy compared with controls.

PMID- 25059036
TI  - Effects of ursolic acid on glucose metabolism, the polyol pathway and
      dyslipidemia in non-obese type 2 diabetic mice.
AB  - Ursolic acid (UA) is a pentacyclic triterpenoid compound that naturally occurs in
      fruits, leaves and flowers of medicinal herbs. This study investigated the dose
      response efficacy of UA (0.01 and 0.05%) on glucose metabolism, the polyol
      pathway and dyslipidemia in streptozotocin/nicotinamide-induced diabetic mice.
      Supplement with both UA doses reduced fasting blood glucose and plasma
      triglyceride levels in non-obese type 2 diabetic mice. High-dose UA significantly
      lowered plasma free fatty acid, total cholesterol and VLDL-cholesterol levels
      compared with the diabetic control mice, while LDL-cholesterol levels were
      reduced with both doses. UA supplement effectively decreased hepatic glucose-6
      phosphatase activity and increased glucokinase activity, the glucokinase/glucose
      6-phosphatase ratio, GLUT2 mRNA levels and glycogen content compared with the
      diabetic control mice. UA supplement attenuated hyperglycemia-induced renal
      hypertrophy and histological changes. Renal aldose reductase activity was higher,
      whereas sorbitol dehydrogenase activity was lower in the diabetic control group
      than in the non-diabetic group. However, UA supplement reversed the biochemical
      changes in polyol pathway to normal values. These results demonstrated that low
      dose UA had preventive potency for diabetic renal complications, which could be
      mediated by changes in hepatic glucose metabolism and the renal polyol pathway.
      High-dose UA was more effective anti-dyslipidemia therapy in non-obese type 2
      diabetic mice.

PMID- 25059037
TI  - Anti-bacterial activity of Achatina CRP and its mechanism of action.
AB  - The physiological role of C-reactive protein (CRP), the classical acute-phase
      protein, is not well documented, despite many reports on biological effects of
      CRP in vitro and in model systems in vivo. It has been suggested that CRP
      protects mice against lethal toxicity of bacterial infections by implementing
      immunological responses. In Achatina fulica CRP is a constitutive multifunctional
      protein in haemolymph and considered responsible for their survival in the
      environment for millions of years. The efficacy of Achatina CRP (ACRP) was tested
      against both Salmonella typhimurium and Bacillus subtilis infections in mice
      where endogenous CRP level is negligible even after inflammatory stimulus.
      Further, growth curves of the bacteria revealed that ACRP (50 microg/mL) is
      bacteriostatic against gram negative salmonellae and bactericidal against gram
      positive bacilli. ACRP induced energy crises in bacterial cells, inhibited key
      carbohydrate metabolic enzymes such as phosphofructokinase in glycolysis,
      isocitrate dehydrogenase in TCA cycle, isocitrate lyase in glyoxylate cycle and
      fructose-1,6-bisphosphatase in gluconeogenesis. ACRP disturbed the homeostasis of
      cellular redox potential as well as reduced glutathione status, which is
      accompanied by an enhanced rate of lipid peroxidation. Annexin V-Cy3/CFDA dual
      staining clearly showed ACRP induced apoptosis-like death in bacterial cell
      population. Moreover, immunoblot analyses also indicated apoptosis-like death in
      ACRP treated bacterial cells, where activation of poly (ADP-ribose) polymerase-1
      (PARP) and caspase-3 was noteworthy. It is concluded that metabolic impairment by
      ACRP in bacterial cells is primarily due to generation of reactive oxygen species
      and ACRP induced anti-bacterial effect is mediated by metabolic impairment
      leading to apoptosis-like death in bacterial cells.

PMID- 25059038
TI  - Evaluation of hepatoprotective activity of vasicinone in mice.
AB  - Justicia adhatoda (vasaka) leaves have long been used in Indian Ayurvedic system
      of medicine as antitussive. Its crude extract has been previously reported to
      have hepatoprotective activity. Vasicinone was isolated from leaves of J.
      adhatoda, column purified and characterized using, TLC UV, FT-IR and 1H NMR. The
      isolated vasicinone was evaluated for hepatoprotective activity using (CCl4)
      induced acute hepatotoxicity model in mice. CCl4 treatments lead to significant
      increase in SGOT, SGPT, ALP levels. Pre-treatment with vasicinone and silymarin
      (25 mg/kg/day for 7 days) significantly decreased these enzyme levels.
      Histopathology of the livers from vasicinone and silymarin pre-treated animals
      showed normal hepatic cords and absence of necrotic changes suggesting pronounced
      recovery from CCl4 induced liver damage. Both vasicinone and silymarin
      significantly decrease the CCl4 mediated increase in pentobarbital indiced
      sleeping time in experimental animals, thus indicating recovery of liver
      function. Based on the above results it can be concluded that vasicinone may act
      as hepatoprotective in mice and warrants further investigation on human
      volunteers.

PMID- 25059039
TI  - Characterization of oleic acid-induced acute respiratory distress syndrome model
      in rat.
AB  - Animal studies using oleic acid (OA) model to produce acute respiratory distress
      syndrome (ARDS) have been inconsistent. Therefore, the present study was
      undertaken to establish an acute model of ARDS in rats using OA and to
      characterize its effect on cardio-respiratory parameters and lethality. The
      trachea, jugular vein and femoral artery of anesthetized adult rats were
      cannulated. A dose of OA (30-90 microL; iv) was injected in each animal and
      changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure
      (MAP) were recorded. Minute ventilation and PaO2/FiO2 (P/F) ratio were also
      determined. At the end, lungs were excised for determination of pulmonary water
      content and histological examination. At all doses of OA, there was immediate
      decrease followed by increase in RF, however at 75 and 90 microL of OA, RF
      decreased abruptly and the animals died by 63 +/- 8.2 min and 19 +/- 6.3 min;
      respectively. In all the groups, HR and MAP changes followed the respiratory
      changes. The minute ventilation increased in a dose-dependent manner while the
      values of P/F ratio decreased correspondingly. Pulmonary edema was induced at all
      doses. Histological examination of the lung showed alveolar damage, microvascular
      congestion, microvascular injury, infiltration of inflammatory cells, pulmonary
      edema and necrosis in a dose-dependent manner. With these results, OA can be used
      to induce different grades of ARDS in rats and OA doses of 50, 60 and 75 microL
      resemble mild, moderate and severe forms of ARDS respectively. Hence, OA model
      serves as a useful tool to study the pathophysiology of ARDS.

PMID- 25059040
TI  - Anti-hyperglycemic activity of rutin in streptozotocin-induced diabetic rats: an
      effect mediated through cytokines, antioxidants and lipid biomarkers.
AB  - Administration of rutin (50 and 100 mg/kg) and pioglitazone (10 mg/kg) orally for
      3 weeks treatment significantly improved body weight, reduced plasma glucose and
      glycosylated hemoglobin, pro-inflammatory cytokines (IL-6 and TNF-alpha),
      restored the depleted liver antioxidant status and serum lipid profile in high
      fat diet + streptozotocin induced type 2 diabetic rats. Rutin treatment also
      improved histo-architecture of beta islets and reversed hypertrophy of
      hepatocytes. Rutin exhibited significant antidiabetic activity, presumably by
      inhibiting inflammatory cytokines, improving antioxidant and plasma lipid
      profiles in High fat diet + streptozotocin induced type 2 diabetic model and may
      be useful as a diabetic modulator along with standard antidiabetic drugs.
      However, such effects need to be confirmed on human subjects in clinical
      condition.

PMID- 25059041
TI  - Influence of environmental hypertonicity on the induction of ureogenesis and
      amino acid metabolism in air-breathing walking catfish (Clarias batrachus,
      Bloch).
AB  - Effect of environmental hypertonicity, due to exposure to 300 mM mannitol
      solution for 7 days, on the induction of ureogenesis and also on amino acid
      metabolism was studied in the air-breathing walking catfish, C. batrachus, which
      is already known to have the capacity to face the problem of osmolarity stress in
      addition to other environmental stresses in its natural habitats. Exposure to
      hypertonic mannitol solution led to reduction of ammonia excretion rate by about
      2-fold with a concomitant increase of urea-N excretion rate by about 2-fold. This
      was accompanied by significant increase in the levels of both ammonia and urea in
      different tissues and also in plasma. Further, the environmental hypertonicity
      also led to significant accumulation of different non-essential free amino acids
      (FAAs) and to some extent the essential FAAs, thereby causing a total increase of
      non-essential FAA pool by 2-3-fold and essential FAA pool by 1.5-2.0-fold in most
      of the tissues studied including the plasma. The activities of three ornithine
      urea cycle (OUC) enzymes such as carbamoyl phosphate synthetase,
      argininosuccinate synthetase and argininosuccinate lyase in liver and kidney
      tissues, and four key amino acid metabolism-related enzymes such as glutamine
      synthetase, glutamate dehydrogenase (reductive amination), alanine
      aminotransaminase and aspartate aminotransaminase were also significantly up
      regulated in different tissues of the fish while exposing to hypertonic
      environment. Thus, more accumulation and excretion of urea-N observed during
      hypertonic exposure were probably associated with the induction of ureogenesis
      through the induced OUC, and the increase of amino acid pool was probably mainly
      associated with the up-regulation of amino acid synthesizing machineries in this
      catfish in hypertonic environment. These might have helped the walking catfish in
      defending the osmotic stress and to acclimatize better under hypertonic
      environment, which is very much uncommon among freshwater teleosts.

PMID- 25059042
TI  - Isolation of mosquitocidal bacteria (Bacillus thuringiensis, B.sphaericus and B.
      cereus) from excreta of arid birds.
AB  - Mosquitocidal bacteria are environmentally friendly alternatives to chemical
      insecticides for controlling mosquitoes and therefore, there have been tremendous
      world-wide efforts to identify novel mosquitocidal bacteria from natural
      environment. In the present study, excreta from arid-birds were analyzed for
      identifying mosquitocidal bacteria. The selection of sample for bacterial
      screening is significant, because, arid-birds are the unique living species and
      gathering the foods from variety of sources from environment. Out of 1000 samples
      examined, twelve bacterial strains were identified as mosquitocidal and the 16S
      rRNA gene sequence alignment depicted that these isolates belonged to Bacillus
      species (Bacillus thuringiensis, B.sphaericus and B. cereus). Toxicity assay
      against mosquito vectors have shown that these isolates are potential. The B.
      sphaericus VCRC-B547 (NCBI: JN377789) has shown a higher toxicity against Cx.
      quinquefasciatus, An. stephensi, and Aed. aegypti. Result from SDS-PAGE has shown
      that there was considerable difference in the protein profiles among the new
      bacterial isolates. Phylogenetic tree with branch length 0.05 revealed three
      distinct groups with homology among the closely related Bacillus strains. This
      study therefore throws considerable interest on the diversity of microbial
      organisms from arid birds and its application in mosquito control.

PMID- 25059043
TI  - A simple and cost effective liquid culture system for the micropropagation of two
      commercially important apple rootstocks.
AB  - The two commercially important apple rootstocks i.e., MM106 and B9 were
      micropropagated using a liquid culture system. Three different strengths of 0.8%
      agar solidified PGR free basal MS medium were first tested to optimize the
      culture media for both the rootstocks. Full strength medium (MS0) supported
      maximum in vitro growth, multiplication, rooting and survival under field
      conditions as opposed to quarter and half strength media. When three different
      volumes of liquid MS0 were tested, highest in vitro growth, multiplication,
      rooting and also survival under field conditions were achieved in 20 mL liquid
      MS0. The cost of one litre of liquid medium was also reduced by 8 times to Rs.
      6.29 as compared to solid medium. The cost of 20 mL medium was further reduced to
      Rs. 0.125.

PMID- 25059044
TI  - Large scale propagation of an exotic edible bamboo, Phyllostachys pubescens Mazel
      ex H. De Lehale (Moso Bamboo) using seeds.
AB  - For ex vitro propagation, seeds of P.pubescens were treated with different
      concentrations of gibberellic acid (GA3) and germination of seeds was tested both
      in plastic pots as well as by direct sowing in the nursery beds. Maximum seed
      germination was achieved when treated with 200 mgL(-1) (w/v) GA3. For in vitro
      propagation, an exposure of nodal explants from in vitro raised seedlings to 0.2
      mgL(-1) 1-phenyl-3-(1,2,3-thiadiazol-5-yl) urea and 1 mgL(-1) kinetin
      supplemented medium for 30 days and thereafter to hormone free Murashige and
      Skoog basal medium resulted in axillary shoot proliferation. For rooting, in
      vitro raised shoots were exposed to MS medium containing 2 mgL(-1) indole-3
      butyric acid for 15 days and then shifted to hormone free medium. On an average,
      2.8 shoots were obtained in 75% of the cultures within 4 weeks. Such in vitro
      raised plants were successfully hardened and shifted to field conditions.

PMID- 25059045
TI  - [The first scene in the editing of the Hongzhi Pharmacopoeia: deciphering the 9th
      of August 1503, in the Ming dynasty].
AB  - On the 9th of August, 1503 the 10th Ming Emperor, Hongzhi, conveyed his desire to
      the Grand Secretariat that the Pharmacopoeia be edited. In response, the Grand
      Secretariat conveyed to the Emperor its intended procedure; namely, to choose two
      directors-general from among the members of the Hanlin Academy and to have the
      Imperial Academy of Medicine actually carry out the editing of the Pharmacopoeia.
      The Imperial Academy of Medicine, however, proposed another idea to the Emperor;
      that Imperial Academy members only be responsible for the editing. In
      consequence, the Grand Secretariat insisted on testing the ability of the
      Imperial Academy members. Though the Hongzhi Emperor agreed with the Grand
      Secretariat's policy and ordered it, the Imperial Academy of Medicine withdrew on
      the grounds that its ability was insufficient. The Hongzhi Emperor consented to
      this and sent a new order that the Hanlin Academy alone should carry out the
      editing. Nonetheless, as a face-saving measure, the Imperial Academy of Medicine
      was chosen to select a member as an editor, and the editing of the Pharmacopoeia
      commenced. The editing was completed on the 3rd of March, 1505, and it was then
      presented to the Hongzhi Emperor. This Pharmacopoeia, was entitled "Yuzhi bencao
      pinhui jinyao," and included a preface by The Hongzhi Emperor.

PMID- 25059046
TI  - [Nicolaus Steno's geometrical description of muscle: the investigation of muscle
      movements in the 17th century].
AB  - Famous geologist Nicolaus Steno (1638-1686) was known as a skillful anatomist in
      his time. His main work about anatomy is "Elementorum myologiae specimen, seu
      musculi descriptio geometrica". Steno introduced geometrical representation into
      muscle study. His purpose was to handle muscle movements in the style of
      Cartesian mechanical philosophy, assuming muscle fibers as the structural and
      functional unit of muscle. Steno modelled muscles as parallelepiped integrations
      of fibers. Steno thought the shortening of muscle fibers modified parallelepiped
      integration and its modification resulted in muscle movements. His parallelepiped
      model enabled the regarding of muscles as objects of physics. Steno's assumption
      and model built a methodological foundation of mechanistic physiology of muscle,
      and influenced latter 17th century thinkers, especially Borelli.

PMID- 25059047
TI  - [Ishido Kanae, a scholar at the Hanaoka Seisyu Medical Institute, and the Imose
      family: a contributor who supported the Hanaoka Medical Institute].
AB  - Ishido Kanae entered the medical school Syunrin-ken which Hanaoka Seisyu
      established in the intercalary year of 1797, the ninth year of the Kansei era. In
      1818, the first year of the Bunsei era, in the Imose family of Seisyu's wife,
      Kae, Kae's older brother died. They had no sons who could carry on the Imose
      name. Ishido Kanae married into the Imose family. Imose Kanae changed his family
      name to "Imose", and managed the Hanaoka Medical Institute, holding positions
      such as assistant professor and dean. In 1826, the ninth year of the Bunsei era,
      Rokujyo, Seisyu's younger brother, became sick. Imose Kanae changed his family
      name to "Hanaoka" and managed the medical school as Sensei, a professor. After
      Hanaoka Seisyu's death, Hanaoka Kanae became the head doctor and supported the
      Hanaoka Medical Institute. But in May, 1840, the eleventh year of the Tenpou era,
      Hanaoka Kanae was buried in the Imose grave plot as Imose-shi Ichidai, one
      generation of the Imose family.

PMID- 25059048
TI  - [Introduction of the psychoprophylactic method and its influence on the prenatal
      care program for institutional parturition in Japan: the practice in the Central
      Hospital of Maternity of the Japanese Red Cross Society and Oomori Red Cross
      Hospital, 1953-1964].
AB  - The psychoprophylactic method is one of the methods for providing 'painless
      childbirth without drugs' and was invented by applying I. Pavlov's theory of
      higher nervous activity. In 1951, it was adopted as a national policy in the
      Union of Soviet Socialist Republics. This method was then introduced in the
      People's Republic of China in 1952. In 1953, it was brought to Japan by Masatomo
      SUGAI, an obstetrician, and was introduced into the Central Hospital of Maternity
      of the Japanese Red Cross Society with the support of the director, Naotarou
      KUJI. The practice of this method by the research team, which consisted of the
      obstetricians and midwives of the Central Hospital of Maternity of the Japanese
      Red Cross Society and Oomori Red Cross Hospital, resulted in the initiation and
      characterization of the prenatal care program to encourage the autonomy of the
      pregnant women for normal parturition in the institutions of Japan.

PMID- 25059049
TI  - [The acceptance of anatomy and physiology in the modern Greek enlightenment].

PMID- 25059050
TI  - [Nutrimetabolomics--the new stage of biochemistry of nutrition. The role of
      nutrilipidomic analysis].
AB  - In this review, in the light of current trends in the development of nutritional
      science and nutritional biochemistry the key directions associated with complex
      comprehensive study of metabolic processes in the body are discussed. We
      highlight the development of lipidomic researches and formation of nutrilipidomic
      analysis. We review the role of different lipids, including omega-3 and omega-6
      PUFAs, in mechanism of protein expression, the nature of lipid-protein
      interactions, and the signaling function of lipids. Since PUFAs influence the
      increase of peroxide oxidation of lipids, this review summarizes current
      methodology used to estimate the oxidative stress.

PMID- 25059051
TI  - [Actual aspects of state control of dietary, clinical and prophylactic nutrition
      in health care organizations].
AB  - A review is aimed to help professionals, who provide state sanitary control of
      dietary (clinical and prophylactic) nutrition in health care organizations.
      Taking into account the new modern legislative framework and the scientific and
      practical publications, the basic requirements for standardization, harmonization
      and individualization (personalization) of nutritional therapy and monitoring of
      their implementation in health care organizations by state sanitary authorities
      has been set out. The attention is focused on the optimization of clinical
      nutrition, as well as the methods of assessment of balance and nutritive value of
      the standard diets, their proper correction with dry protein composite blends and
      other specialized products of dietary clinical and prophylactic nutrition,
      including foods fortified with dietary and biologically active substances and
      food supplements (nutraceuticals). The paper describes ways to improve the
      organization of state sanitary and dietary nutritional care in health care
      organizations, outlines priority issues to be addressed to improve the
      nutritional care.

PMID- 25059052
TI  - [The effect of muscle load on the post-prandial content of blood serum hydrolytic
      enzymes in men with different levels and specificity of daily physical activity].
AB  - The article presents data on the effect of the combined action of food and
      muscular load on the level of hydrolytic enzymes in blood serum of healthy young
      people 18-22 years old, with various levels of adaptation to the effects of
      physical activity. The first group (n = 8) of the examined persons were high
      qualified athletes developing their speed and power qualities in anaerobic
      energetic regime (Greco-Roman wrestling, sambo, judo). The second group (n = 8)
      were athletes developing endurance in aerobic energetic regime (skiers, track and
      field athletes--stayers, biathletes). The control group (n = 8) consists of non
      athletes. The content of hydrolytic enzymes: pepsinogen-1, pepsinogen-2, the
      activity of pancreatic alpha-amylase, lipase were defined by ELISA. The content
      and activity of ferments were defined in blood serum, taken in the morning
      fasting and post-prandial period in dynamics after 15, 45, 75 and 105 min after
      administration of the test breakfast (100 g of ground boiled beef and 200 ml of
      unsweetened tea) in a state of relative physiological rest and after the
      veloergometric exercise muscular load (at the level of 60-70% of maximal oxygen
      consumption) during an hour (in 7-14 days). Multidirectional changes of
      concentration of investigated enzymes in the postprandial period among examined
      were defined in the conditions of relative physiological rest and under the
      action of the muscular tension. For groups of athletes higher alpha-amylase and
      lipase blood activity were characteristic both in a state of physiological rest
      and under the action of muscular load. It was also determined that after the
      muscular tension there was an increase in activity of alpha-amylase at 75 min and
      lipases at 15 min relative to background indicators at non-athletes. For the
      athletes from the second group the increase (p < 0.01) relative to background
      data of activity as alpha-amylase as lipase on an empty stomach was noted.
      However postprandial (15-45 min) alpha-amylase (p < 0.05) and lipase (p < 0.001)
      activity was significantly decreased. At relatively high rates of fasting alpha
      amylase activity there was a decrease of its level in the postprandial period,
      whereas at low rates of enzyme activity on an empty stomach its increase can be
      occurred in the postprandial period. Lipase activity changed in groups of
      athletes unidirectionally, it decreased (p < 0.01) in athletes of the first group
      at 45 min. and in athletes from the second group at 15-105 min (p < 0.001). For
      athletes of the first group, also as well for non-athletes, significantly lower
      blood lipase activity was noted at rest and in the conditions of muscular
      tension. After a physical load lipase activity in athletes from the second group
      was decreased throughout the postprandial period. Blood serum concentration of
      pepsinogen-1 and pepsinogen-2 were also significantly higher in the groups of
      athletes, but only in fasting conditions. After receiving the breakfast the
      content of these proenzymes were significantly lower in athletes comparable to
      the control group. Pepsinogen-2 concentration had a strong tendency to
      significant decrease after muscular exercise in all athletes throughout the
      postprandial period (at 15 and 105 min). For the athletes from the first group a
      decrease of pepsinogen-2 concentration to the values accepted as a norm (4-22
      microg/l) was tended. The obtained data suggest that the revealed changes are
      associated with a sport orientation and a level of daily physical activity.

PMID- 25059053
TI  - [The effect of diet ratio of polyunsaturated fatty acids of omega-3 and omega-6
      families on activity of aminotransferases and gamma-glutamyltransferase in rat
      blood serum].
AB  - The effect of diet fat compositions with various ratio of omega-3 and omega-6
      polyunsaturated fatty acids (PUFAs) on alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and gamma-glutamyltransferase (GGT) activities in blood
      serum of 45 white mongrel rats weighing 90-110 g (9 animals in group) has been
      investigated. Fat components in the semi-synthetic diet, compiled on the basis of
      AIN-93 diet, and sources of omega-6 and omega-3 PUFA were presented by sunflower
      oil, soybean oil and fish oil. It has been shown that four-week inclusion of
      linoleic acid (LA) and alpha-linolenic acid (alpha-LNA) in a ratio of 7:1 into
      the diet (soybean oil) as well as use of only omega-6 PUFA (sunflower oil) has
      lead to an increase in the activity of ALT and GGT in rat blood serum compared to
      control animals treated with the complex of linolenic, eicosapentaenoic (EPA) and
      docosahexaenoic (DHA) acid through the mixture of sunflower oil and fish oil
      (9:1) with the ratio of omega-6 and omega-3 PUFA 7:1. Along with this, the
      AST:ALT ratio (de Ritis ratio) was lower (p < 0.05) as compared with the control
      group of rat, amounting respectively 0.92 +/- 0.08 and 0.79 +/- 0.12 vs 1.26 +/-
      0.10. The use of high doses of omega-3 fatty acids (600 mg EPA and 400 mg DHA per
      kg of animal weight per day coming through fish oil) did not affect the activity
      of ALT and GGT, but increased AST serum activity (0.47 +/- 0.04 micromoles/min
      per mg protein) and the de Ritis ratio (2.53 +/- 0.23). The diet deprived with
      fat increased enzyme activity of ALT, AST and GGT in rat blood serum.

PMID- 25059054
TI  - [Effects of dietary fibers on hepatocyte apoptosis in rats with alimentary
      polyhypovitaminosis].
AB  - The effect of dietary fibers (DF) of wheat bran on hepatocyte apoptosis in rats
      adequately provided with vitamins or insufficiently supplied with vitamins has
      been investigated. 48 male Wistar rats (initial body mass--58.1 +/- 0.5 g) were
      randomly divided into 6 groups and fed with semi-synthetic diet, containing 100%
      or 20% of vitamin mixture (Vit) with or without addition of DF in the dose
      corresponding to the upper allowable level of its consumption (5% of diet mass)
      for 4 weeks. The animals of the 1 group received 100% of vitamin mixture (100%
      Vit); 2 group--100% Vit + DF; 3 group--20% of vitamin mixture with full exclusion
      of vitamins E, B1 and B2 (20% Vit); 4 group--20% of vitamin mixture and DF (20%
      Vit + DF). The next 5 days rats from vitamin-deficient groups were fed with diets
      supplemented with 80% of vitamins from their content in control group: (5 group-
      20% Vit + 80% Vit; 6 group--20% Vit + DF + 80% Vit). The suspension of
      hepatocytes was received by Becton Dickinson Medimachine System (USA). Hepatocyte
      apoptosis was assessed by the method of flow cytometry using Beckman Coulter FC
      500 (USA) cytometer by stained cells with Annexin V-FITC/ 7-Amino-Actinomycin D
      Kit (Beckman Coulter, USA). In rats fed complete semi-synthetic diet supplemented
      with DF (100% Vit + DF) the hepatocyte apoptosis was higher by 22% (p < 0.10)
      than that in rats of control group (4.99 +/- 1.82%). In rats fed diets with low
      vitamin content (groups: 20% Vit and 20% Vit + DF) the hepatocyte apoptosis was
      significantly higher (p < 0.05) than that in the control group and reached 7.03
      +/- 1.74 and 7.26 +/- 1.13% accordingly. Normalization of vitamin content in the
      diets of rats from deficient groups during 5 days had no effect on the severity
      of apoptosis regardless from presence (8.02 +/- 2.18%) or absence of the DF (8.04
      +/- 1.66%). Adding DF in dose corresponding to the upper allowable level of
      consumption, on the background of adequate vitamin content in the diet is
      accompanied by a tendency to develop hepatocyte apoptosis, which may be the
      result of a direct action of short chain fatty acids generated from the DF and
      the deterioration of vitamin sufficiency.

PMID- 25059055
TI  - [Influence of nutritional patterns on the severity of acne in young adults].
AB  - Currently, one of discussed questions of acne etiopathogenesis is alimentary
      factors, in particular, national dietary habits at different regions and the role
      of diet. The purpose of this research: from the standpoint of evidence-based
      medicine to reveal the influence of dietary intake (energy value of the diet,
      macro- and micronutrients content) on the actual severity of acne in young
      people. We observed 180 respondents aged 15 to 25 years. The main group included
      90 patients with moderate to severe acne, who were treated at the Center for
      Dermatology and prevention of sexually transmitted diseases in Astana, including
      38 girls and 52 boys, mean age 20.5 +/- 4.3 years. The control group consisted of
      90 apparently healthy subjects (36 girls and 54 boys, mean age 19.8 +/- 4.2
      years) without even a single manifestation of non-inflammatory or inflammatory
      acne elements. Studying the actual food consumption was carried out by a 24-hour
      (daily) food recall using specially designed questionnaires and albums. RESULTS:
      regular meals with excess energy value significantly contributes to the
      progression of disease severity in young people with acne [the power of influence
      in young men was 0.43 (43%), girls--0.42 (42%)], the excess of the normal daily
      requirements for carbohydrates also significantly affect the severity of acne
      [the power of influence in young men--0.23 (23%), in girls--0.35 (35%)], lack of
      vitamin A (retinol) and its provitamin (carotene) significantly affect the
      severity of acne (the power of influence in young men--0.44 (44%) and 0.42 (42%),
      respectively, in girls--0.46 (46%) and 0.31 (31%), respectively); in young men
      with severe acne vitamin D deficiency with a force of 0.3 (30%) significantly
      potentiates the inflammatory process; lack of zinc in the diet significantly
      affects the severity of the pathological process in severe forms of acne, the
      power of influence of this micronutrient in young men--0.44 (44%), women--0.34
      (34%).

PMID- 25059056
TI  - [The prevalence of food allergy to peanut and hazelnut in children in Tomsk
      Region].
AB  - Food allergy to peanuts and nuts is an actual problem of practical health care,
      associated with significant prevalence of this disease, severe clinical symptoms
      and difficulty of diet organization. Purpose of the study--to study the
      prevalence of food allergy to peanut and hazelnut in Russian children, the
      investigation of clinical characteristics of this disease, and the mechanisms of
      sensitization to allergen components. The cross-sectional study was performed in
      the framework of the EuroPrevall (No FP6-2006-TTC-TU-5 Proposal 045879). The
      first stage was performed in random samples of primary schoolchildren aged 7-10
      years (n = 13 010) from the Tomsk Region, Russia using a standardized
      questionnaire. The case-control sample was recruited for the second stage (n =
      1288). Thus who reported adverse reactions to food in the screening stage were
      considered as cases (n = 652), children without reported reactions were controls
      (n = 636). The case-control stage included the completion of a clinical
      questionnaire, skin-prick test (ALK-Abelly, Spain), serum specific IgE
      measurement and component-resolved diagnostic: IgE measurement of allergen
      components of peanut (Ara h1, Ara h26, Ara h34, Ara h8), hazelnut (Cor a1, Cor
      a8, Cor a11) and birch allergen Bet v1 (ImmunoCAP, Phadia, Sweden). The
      prevalence of food allergy to peanut and hazelnut in children aged 7-10 years in
      the Tomsk region is 0.08 and 0.09%, respectively. The manifestation of the food
      allergy to nuts occurs in the preschool years, main reactions associated with
      allergy to nuts were oral allergy syndrome (75-80%), gastrointestinal disorders
      (60-80%) and itching skin rash (20-50%). Sensitization to birch is significantly
      correlated with the level of specific IgE to hazelnut (r = 0.53, p < 0.05) and
      peanut (r = 0.56, p < 0.05). Sensitization to heat-labile proteins peanut Ara h8
      (12.3%) and hazelnut Cor a1 (8.8%) (homologues of Bet v1) dominates in the sample
      of children with food sensitization, that determines the cross-reactivity
      mechanism in the formation of food sensitization in the studied sample. The
      prevalence of allergies to peanut and hazelnut in Russia is much lower than in
      Europe and North America. Sensitization to these foods develops by the mechanism
      of cross-reactivity with birch pollen allergen. This type of sensitization
      determines mild clinical symptoms of allergy to hazelnut and peanut.

PMID- 25059057
TI  - [Can cross-allergic reactions to food antigens be the cause of recurrent
      pancreatitis in children with food allergies?].
AB  - Drug and food allergy in 80% of cases are the cause of duodenal inflammation
      disrupting the function of the pancreatic ducts. However, in some cases,
      elimination diet in patients with food allergy does not provide a sufficient
      effect. The article shows the effect of cross-allergic reactions on recurrent
      pancreatitis in 28 children with food allergy (mean age 11.7 +/- 2.9 years). As
      an additional diagnostic criterion the coefficient of degranulation of mast cell
      in the intestinal mucosa (the ratio of degranulated forms to granulated) was
      determined, through which the effect of cross-allergic reactions (between food
      antigens and drugs of animal origin) on the duration and frequency of
      exacerbations of chronic pancreatitis in children with food sensitization has
      been shown. The exception of enzyme preparations for children with sensitization
      to pork and exception of eubiotics prepared using sucrose-gelatin-milk medium for
      children with sensitization to cow's milk and beef led to feel better in a
      shorter time (2-3 days) and to reduce the frequency of relapses. Catamnesis
      observation for 3 years showed that the incidence of recurrent exacerbations of
      the disease in 11 children with excepted cross-allergic reactions in the first
      year of follow-up was 9.1%, in the second year--9.1% and in the third year--0%,
      while in control group (17 children) the frequency of exacerbations was
      respectively 23.5; 35.3; 35.3%. In patients of the main group there was a slight
      overall increase of mast cells in the intestinal mucosa from 211.7 to 230.2 mm2
      (p > 0.05) with decreasing of degranulated forms from 163.6 to 138.71 mm2 (p >
      0.05) and significant increase of granulated forms from 47.41 to 91.51 mm2 (p <
      0.05), resulting in a significant decrease in mast cells degranulation
      coefficient from 3.2 +/- 0.62/mm2 to 1.24 +/- 0.26/mm2 (p < 0.0001). Thus,
      duodenal etiology of recurrent pancreatitis caused by exposure to food antigens
      or cross-allergic reactions can be diagnosed with an additional diagnostic
      criterion--the coefficient of mast cell degranulation, whose exponents greater
      than 1.5 indicate evidence of antigenic exposure to the mucosa of the duodenum
      and allergic inflammation.

PMID- 25059058
TI  - [Comparative analysis of ergogenic efficacy of energy drinks components (caffeine
      and bitter orange extract) in combination with alcohol].
AB  - Estimation of ergogenic effects of caffeine and bitter orange exract combined
      with alcohol is presented in the article. Investigations were performed on 3
      groups (8 animals in each group) of male Wistar rats aged 4 months. Animals in
      group 1 were treated orally for 7 days, the mixture comprising caffeine and
      alcohol (0.6 g of caffeine, 72 ml of ethanol, water to 1 liter) in an amount
      equivalent to 4.28 mg caffeine per kg of body weight. Animals in group 2 received
      a mixture containing bitter orange extract and alcohol (1 g bitter orange
      extract, 72 ml of ethanol, water to 1 liter) in an amount equivalent to 0.43 mg
      of synephrine per kg body weight. Animals in the control group received the same
      volume (7.1 ml/kg) 7.2% aqueous solution of ethanol. Group of animals consumed
      caffeine in mixture with alcohol and the control group exhibited a significant
      weight gain, while the body weight of animals treated with the extract of bitter
      orange didn't significantly change. Using the methodology of the open field the
      effects of caffeine and bitter orange extract in combination with alcohol on the
      ratio of the active components of the orienting-exploratory behavior and passive
      defensive behavior have been determined. Administration of mixture with caffeine
      increased locomotory activity by 164%, administration of bitter orange extract
      didn't affect this performance. Introduction of caffeine containing mixture
      significantly reduced the level of situational anxiety, which was manifested in
      the reduction of time spent by the animal in the center of the arena. The effects
      of ergogenic components on the performance of static and dynamic muscle endurance
      have been investigated. Single administration of the mixture containing caffeine,
      after 30 min caused a significant increase in performance and, consequently,
      endurance of glycolytic muscle fibers measured using the "inverted grid" test.
      Animals from this group produced 186% more work compared with control animals.
      Acute administration of bitter orange extract did not cause significant changes
      in static endurance. At the same time after 7 days of its daily administration a
      slight increase in dynamic endurance (test "treadmill") has been determined,
      which was expressed in some increase in the amount of work done by animals fed
      bitter orange extract compared with the control group of animals. Death of 1
      animal in the group consumed bitter orange exract mixture with alcohol indicates
      potential risks of synephrine consumation together with alcohol.

PMID- 25059059
TI  - [Amaranth flour: characteristics, comparative analysis, application
      possibilities].
AB  - Amaranth flour--a product of amaranth seeds processing--is a valuable industrial
      raw material that has an unique chemical composition and may be used for
      nutrition of people suffering from intolerance to traditional cereals protein,
      including celiac disease patients. The research aim was to study the composition
      of amaranth flour of two types compared with semolina which is traditionally used
      for nutrition by Russian population, as well as to compare the composition of
      milk amaranth flour porridge with milk semolina porridge. The composition of
      amaranth whole-ground flour and amaranth flour of premium grade processed from
      amaranth seeds grown in Voronezh region has been researched. It is to be noted
      that protein content in amaranth flour was 10.8-24.3% higher than in semolina,
      and its biological value and NPU-coefficient were higher by 22.65 and 46.51%
      respectively; lysine score in amaranth flour protein of premium grade came up to
      107.54%, and in semolina protein only 40.95%. The level of digestible
      carbohydrates, including starch, was lower in amaranth flour than in semolina by
      2.79-12.85 and 4.76-15.85% respectively, while fiber content was 15.5-30 fold
      higher. Fat content in amaranth flour of premium grade was 2,4 fold lower than in
      whole-ground amaranth flour but it was 45% higher than in semolina. The main
      advantage of amaranth flour protein compared to wheat protein is the predominance
      of albumins and globulins and a minimal content of prolamines and alpha-gliadin
      complete absence. The specifics of chemical composition allow the amaranth flour
      to be recommended for being included into nutrition of both healthy children and
      adults and also celiac disease patients.

PMID- 25059060
TI  - [Determination of major metal cations in juices and nectars by capillary zone
      electrophoresis].
AB  - The method of determination of potassium, sodium, calcium and magnesium cations
      by capillary zone electrophoresis (using lithium cations as the internal
      standard) in the juices and nectars was advised. Optimal conditions for
      electrophoretic separation: pH value of the working buffer (pH 3.6), the
      concentration of imidazole (contrast agent 15-20 mmol/dm3), the concentration of
      18-crown-6 ether (2 mmol/dm3). The method was tested on 15 samples of juices and
      nectars. The results of determination of potassium and magnesium cations were
      compared with results obtained by mass spectrometry with inductively coupled
      plasma. The equation of the linear regression and R-squared value for
      determinations of magnesium cations were defined as: y = 0.999x + 3.29; R =
      0.952; for determination of potassium cations: y = 0.959x + 51.94; R = 0.997;
      indicating good the correlation between the data obtained by these methods.

PMID- 25059061
TI  - [Contribution of military doctor Roman S. Chetyrkin in the formation and
      development of medicine in Russia].
AB  - The article deals with an extensive and diverse activities of prominent military
      doctor Roman Sergeyevich Chetyrkin, who contributed greatly to the development of
      hygiene and epidemiology in Russia. He had a lot of merit as a talented organizer
      of military and civilian health care. Special attention is paid to the
      Chetyrkin's contribution to the development of military medical expertise because
      of his works in this direction are fundamental for this science.

PMID- 25059062
TI  - [Mikhail Fedorovich Nesterin (to the 85th anniversary of birthday)].

PMID- 25059063
TI  - [A review of current methods for nutrimetabolomic and proteomic research in
      biochemistry of nutrition].
AB  - At present biochemistry of nutrition involves the use of OMICs to investigate
      food quality, safety, bioactivity and nutrition mechanisms. In this context,
      nutrimetabolomics is one of the latest directions of nutrition development and
      provides a better understanding of the influence of nutritional factors on the
      metabolic pathways of the organism. Proteomic methods play an important role in
      nutrimetabolomics and allow to detect, identify and quantify proteins under
      different conditions. Variety of technical and methodological advances,
      improvements in bioinformatics and possibility of tandem use of different methods
      helps to solve a number of basic and applied science's problems. Currently huge
      amount of qualitative and quantitative data on the structure, functions and
      activities of proteins and their interactions is accumulated. Proteomics aims to
      establish and characterize a complete set of proteins of the organism. This
      review summarizes the basic applications of proteomics used in nutrimetabolomic
      researches. The advantages and disadvantages of the most common techniques of
      protein separation and sample ionization, types of mass analyzers, basic
      approaches to the identification of proteins and most widely used databases of
      known biological sequences are overviewed with a critical assessment of
      challenges and potential applications.

PMID- 25059064
TI  - [Phytoecdysteroids influence on the hormonal status and apoptosis in growing
      rats].
AB  - The impact of the 15-day consumption of Serratula coronata extract containing
      phytoecdysteroids on some indicators of hormonal status and activity of apoptosis
      in various organs of growing male Wistar rats (initial body weight 127.8 +/-2.5
      sigma) has been studied. The extract from the leaves of Serratula coronata was
      added to the water of animals of experimental groups 2 and 3 (n = 8 in each
      group) daily at the dose of 5 and 15 mg phytoecdysteroids per kg of body weight
      respectively. Animals of the control group 1 (n = 8) received water alone
      throughout the experiment. Daily volume of drunk fluid was recorded. At the 15th
      day of the experiment animals were taken out using the decapitation under the
      light ether anesthesia. The content of corticosterone, prostaglandin E2 and beta
      endorphin in rat blood plasma were determined by ELISA test. Plasma level of
      noradrenaline was determined by HPLC. DNA damage and percentage of apoptotic
      cells (apoptotic index) were measured in isolated cells of the thymus, heart and
      brain by single-cell gel electrophoresis (the comet assay). Significantly lower
      concentration of norepinephrine was detected in plasma of experimental animals
      from groups 2 and 3 (10.3 +/- 1.1 and 7.2 +/- 0.8 ng/ml, respectively) compared
      to the same index in the control group (20.4 +/- 3.4 ng/ml). Significant
      differences of other biochemical parameters for all groups of animals have not
      been identified. Statistical significant difference in the ratio of
      corticosterone/norepinephrine compared with control animals was detected for a
      group of rats consumed the highest dose of phytoecdysteroids. There was no
      statistically significant difference in DNA fragmentation and apoptosis index in
      animals consumed phytoecdysteroids in compare with the control group of animals.
      The absence of the activity of apoptosis in cells of the heart, brain and thymus
      of rats treated with phytoecdysteroid extract may indicate the safety of its use
      in the diet of the animals.

PMID- 25059065
TI  - [Soluble apoptosis markers in obese patients with food intolerance].
AB  - For the soluble apoptosis markers study 151 patients with obesity (92 women and
      59 men) aged between 18 and 63 years were examined. Diagnosis and degree of
      obesity was based on the body mass index (38.2 +/- 5.4 kg/m2). Generally food
      intolerance was identified in 36.4% of obese patients. Four groups of patients
      were formed: three groups of patients with obesity stage I (15 patients), II (18
      patients) and III (22 patients), respectively, and with food intolerance, and a
      group of obese patients without food intolerance (control group, n = 31). Obese
      patients with food intolerance received standard version of hypocaloric diet with
      the exception of specific food allergens. Duration of observation was 39-43 days.
      Such soluble apoptosis markers as sFas-L, Caspase-9, Caspase-8 and sCD153 were
      significantly higher in stage III obesity patients compared obese patients
      without food allergy (0.120 +/- 0.030 vs 0.035 +/- 0.010; 13.2 +/- 3.2 vs 5.9 +/-
      0.4; 1.4 +/- 0.18 vs 0.6 +/- 0.24; 0.123 +/- 0.010 vs 0.025 +/- 0.002 ng/ml
      respectively). Positive dynamic of sFas-L, Caspase-9 and Caspase-8 (decrease to
      0.052 +/- 0.030; 7.7 +/- 2.2 and 0.4 +/- 0.18 ng/ml respectively) in patients
      with obesity stage III and intactness sCD153 during diet therapy course were
      revealed. Significant differences for only Caspase-9 in patients with obesity
      stage II were obtained. The data obtained are considered as normalization of
      apoptosis due to nutritional correction of immunological disorders. Study of sFas
      L, Caspase-9 and Caspase-8 allows to predict the course of disease, as
      immunological research for early detection of food allergy makes possible to
      implement the principles of personalized diet therapy.

PMID- 25059066
TI  - [Effect of wheat bran fiber on vitamin status of weaning rats with alimentary
      polyhypovitaminosis].
AB  - Effect of wheat bran on the vitamin status of rats adequately provided with
      vitamins or insufficiently supplied with vitamins has been investigated. 32 male
      Wistar weaning rats (initial body mass--49-67g) were randomly divided into 4
      groups and fed with complete semi-synthetic diet, containing 100 or 20% of
      vitamin mixture with or without addition of wheat bran (5% of diet mass) for 35
      days. The animals of the control group received 100% of vitamin mixture without
      adding of wheat bran; 2 group--received those diet with wheat bran; 3 deficient
      group--20% of vitamin mixture with full exclusion of vitamins E, B1 and B2; 4
      group--20% of vitamin mixture and wheat bran. The inclusion of wheat bran in full
      semi-synthetic diet has been accompanied by significant decrease of alpha
      tocopherol liver content on 17% (p = 0.006), significant increase of vitamin B1
      liver level on the 16% (p = 0.027) and blood plasma vitamin D elevation on 19% (p
      = 0.017), as well as a tendency (p = 0.059) to increase the liver level of
      vitamin B2. Indicators of vitamin A status as well as plasma vitamin E
      concentration, liver and blood plasma MDA levels were not changed in this group
      rats. The 5-fold reduction of the vitamin mixture quota and the exclusion of
      vitamins E, B1 and B2 resulted in a significant (p < 0.05) 1.6-1.8 fold decreased
      in animal body weight and liver mass and the manifestation of the deep external
      signs of vitamin deficiency. Young animals were more sensitive than adult animals
      to a lack of vitamins in the diet. Vitamin A (retinol palmitate) liver content in
      rats from this group was 25.1-fold reduced, vitamin E (alpha-tocopherol)--2.1
      fold, vitamins B1 and B2--by 57 and 38% compared with animals received a complete
      control diet (p < 0.05). Blood plasma concentration of vitamins A, E, D was 19
      34% decreased. Adding of bran in vitamin deficit diet led to increased
      consumption of vitamin B--on 40%, vitamins B2 and E--21%, both due to their
      natural content in the bran, and as a result of increased eatability of the feed
      by 16% relative to deficient group due to improved taste of the diet. Enrichment
      of vitamin scarce diet with wheat bran led to an increase in body weight by 56%,
      the efficiency of the diet by 67%. This circumstance didn't allow to reveal the
      effect of dietary fiber on the vitamin status of rats with polyhypovitaminosis.
      The significant (p < 0.05) increase of retinol plasma level by 34% and liver and
      blood plasma tocopherol content by 17% and 22% and reduction of MDA blood plasma
      level by 24% took place in animals from this group compared to a group of rats
      receiving vitamin deficit diet without any effect on liver MDA level, liver
      vitamin A, B1 and B2 content and heart coenzyme Q10 level. The results obtained
      suggest that wheat bran inclusion in the diet of rats adequately supplied with
      vitamins may lead to a deficiency of vitamin E.

PMID- 25059067
TI  - [Regional features of obesity-associated gene polymorphism (rs9939609 FTO gene
      and gene Trp64Arg ADRB3) in Russian population].
AB  - Recent studies have shown a significant association with obesity polymorphisms:
      rs9939609 gene due to fat mass and obesity FTO in European and some Asian and
      African American populations Trp64Arg ADRB3 gene in several European populations.
      Association of variants rs9939609 and Trp64Arg obesity was studied in 1244 the
      inhabitants of Moscow and Sverdlovsk regions. Genotyping was performed using
      allele-specific amplification, detection results in real time using TaqMan-probes
      complementary DNA polymorphic sites. The frequency of the mutant allele of the
      FTO gene in the population of Moscow and Sverdlovsk region was 45.1%, with the TT
      genotype was detected in 30.2% of cases, AT--49.5%, AA--20.3%. Women had the
      presence of the mutant allele more likely than men (48.4 vs. 42.5%). People with
      obesity were more genotypes AA (26.3%) and AT (52.8%) compared to the surveyed
      with a BMI of less than 30 kg/m2 (respectively 18.1 and 50.7%). A significantly
      higher incidence of risk allele A was found in individuals with obesity (52.6 and
      43.4%). The presence of the mutant allele of the gene ADRB3 among the population
      of Moscow and Sverdlovsk regions was noted in 7.4% of cases. While 15.5% of
      patients had a heterozygous genotype Trp64Arg ADRB3, that is consistent with
      international research. The frequency of the risk allele and genotype Arg64
      Trp64Arg in women (9.3 and 18.5%) was significantly higher than men (6.2 and
      12.2%). The presence of the mutant allele and genotype Trp64Arg ADRB3
      (respectively, 9.1 and 18.1%) were significantly more marked in the examined
      obese compared with those with a body mass index less than 30 kg/m2 (7.4 and
      14.9%), but these differences were not statistically significant. The results of
      these studies suggest that genetic variants of the FTO gene rs9939609 genotype
      and Trp64Arg ADRB3 contribute to the development of obesity among residents of
      Moscow and Sverdlovsk Region of Russia. The risk of obesity increases in the case
      of combined polymorphisms in both genes.

PMID- 25059068
TI  - [Toxicological assessment of nanostructured silica. The acute oral toxicity].
AB  - Nanostructured amorphous silica (SiO2) is one of the priorities of nanomaterials,
      exposing human to the ever-increasing scale as a component of food additives,
      drugs and cosmetic products. According to numerous publications SiO2
      nanoparticles (NPs) possess deleterious effects on animal and human cells in
      vitro and also exhibit inhalation toxicity. However, the biological effects in
      vivo of silica NPs taken orally are studied insufficiently. This article
      represents the first section of this study which aim is identification of silica
      preparation as nanomaterial and estimating of acute toxicity after oral
      administration in the form of aqueous suspension. Studies of size and shape of
      the particles in aqueous suspension of silica used in the study by electron and
      atomic force microscopy, spectroaqustic analysis and dynamic laser light
      scattering showed that the test substance is a nanomaterial. Estimation of acute
      toxicity of an aqueous suspension of nanostructured silica with a single
      intragastric gavage to male BALB/C mice allowed to conclude that the test
      material has LD50 by the oral route greater than 10 000 mg/kg and consequently
      belongs to class IV (low danger agents). Pathological changes in jejunum and
      colon of mice in the acute experiment (at a dose of 10 000 mg/kg) haven't been
      identified. Thus SiO2 NPs possess low toxicity when administered in the
      gastrointestinal tract. The available data, however, do not exclude possible
      presence of adverse effects under their long-term administration by oral way.

PMID- 25059069
TI  - [Effect of phytosterols and alkylglycerols in the diet on morphometric indicators
      of liver structure in rats].
AB  - In the experiment where rats were fed a diet with phytosterols and alkylglycerols
      for 1,5 months, changes were observed in morphometric parameters in the liver
      structure in rats. In animals, which were fed a diet with 20% replacement of the
      fat component (lard) on phytosterols (stanols derived from rapeseed and
      conifers), blood circulatory disorders of the liver were observed. There was
      dilatation of the lumens of the central veins and hepatic veins in the
      interlobular vascular bundles. On the periphery of the lobules, around the
      vascular bundles, abundant clusters of lymphocytes were revealed. In both groups
      of rats fed a diet containing various amounts of alkylglycerols obtained from
      Berrytenthis magister liver (7 and 50 mg per day) and lard as a fat component, in
      peripheral areas of hepatic lobules the reticuloendothelial cell count was
      increased as compared with the control group of animals fed a diet containing as
      fatty component a mixture of lard and sunflower oil (1:1). These cells contained
      polysaccharides in the cytoplasm and formed thin bands along the hepatic tubules.
      In addition, in all groups of rats receiving diets with lipid components (both
      stanols and alkylglycerols), the occurrence of reticuloendothelium proliferation
      foci in the middle and central zones of liver lobules were 1,8, 2,3 and 2,1 fold
      higher than in control group. As compared to control animals, the foci in the
      above groups contained 1,8, 1,7 and 1,6 fold more cells. Furthermore, the number
      of animals with reticuloendothelium proliferation foci in the groups receiving
      investigated lipid components was also increased by 2 fold, as compared to
      controls.

PMID- 25059070
TI  - [Influence of titanium dioxide and silica nanoparticles on accumulation and
      toxicity of lead in experiments with intragastric co-administration].
AB  - The aim of this work was experimental verification of assumptions about the
      possibility of potentiation of accumulation and toxicity of lead (Pb) after its
      joint intragastric administration with nanoparticles (NPs) of titanium dioxide
      (TiO2) and silica (SiO2). Lead acetate was administered intragastrically to rats
      at a dose of 20 mg/kg body weight of lead over 21-23 days as a solution in water
      or in aqueous slurry of TiO2 or SiO2 NPs taken at 1 and 100 mg/kg body weight.
      The data was obtained that co-administration of Pb with NPs of SiO2 and TiO2 led
      to changes in a number of indicators that can be interpreted as a slight increase
      in the toxic effect of the tested substances. However, the size and direction of
      identified effects depended on the type and the dose of NPs of both kinds. In
      coadministration of Pb with NPs of TiO2 at both doses (rats with initial body
      mass 80 +/- 8 g) there was a decrease in hemoglobin concentration on 24% (p <
      0.05), number of lymphocytes on 13% (p < 0.05), and platelets on 10% (p < 0.05)
      in the blood, together with the activation of apoptosis in hepatocytes.
      Introduction of Pb with SiO2 NPs (rats with initial body mass 140 +/- 4 g)
      contrary resulted in increased concentration of hemoglobin on 24% (p < 0.05) and
      significant decrease of urinary excretion of 5-aminolevulinic acid. Accumulation
      of Pb coadministered with TiO2 was not influenced in liver and decreased in
      spleen on 50% (p < 0.05), testis on 79% (p < 0.05) and brain on 38% (p < 0.05).
      SiO2 had no influence on these indices. It is concluded, that the hypothesis
      about Pb toxicity facilitation due to its transport across the intestinal wall in
      the form adsorbed on the NPs, does not receive experimental verification, and the
      observed effects were most likely due to both the toxicity of the Pb, and
      toxicity (in the studied doses) of NPs studied.

PMID- 25059071
TI  - [The structure of the nourishment of preschoolers during the weekend (short
      report)].
AB  - To study the feeding of 190 children aged 3-7 years attending 4 preschool
      educational institutions in the city Mezhdurechensk, Kemerovo region, at home on
      weekends questionnaires were conducted by the parents. Studies have shown that
      multiple meals in 57% of children was 5 times a day, 43% of children--4 times a
      day, including snacks; 97% of children have at breakfast main dish, drinks and
      sandwiches and only 3% of children have breakfast that did not meet standards for
      structure and was insufficient and inadequate to cover subsistence expenses of
      energy, because consisted of a sandwich and a drink. Only 7% of preschooler's
      lunch met recommendations on its structure and included the first, main dish,
      salad and drink, lunch of 93% of children included only one hot dish (first
      course, or the second). Dinner in volume, compared with the recommended
      standards, was redundant on average 57% of preschoolers since consisted of
      sandwiches, salad, meat dish and side, drink. Children's snacking during the day
      included the following suite of products: sandwiches (with sausage, cheese,
      butter), tea with sweets (candies, chocolate), fermented milk drink, fruits. When
      examining the frequency of meals during the day on weekends, there is a tendency
      to use the same dishes (what children ate for lunch, they eat at dinner on the
      same day, and then for breakfast on Sunday). The study of the structure of meals
      in pre-school children at home during the days of the week (evening meal) found
      that in most cases (67.8%) their dinner was irrational, the structure was
      identical to the structure of the adults of the family (fried dishes: fried pies,
      fried potatoes, sodas). Irrationally organized meals for children at the weekend
      showed inadequate knowledge of parents on the healthy diet for their child at
      home.

PMID- 25059072
TI  - [Historical journey to infant feeding].
AB  - The article provides an overview of the available literature on problems of
      infant nutrition, and shows the historical development of the principles of
      infant feeding. It discusses in greater detail the use of goat milk as a basis
      for infant nutrition. It notes the need for a comparative analysis of breast milk
      substitutes, and for clinical studies evaluating the value of goat milk in infant
      nutrition.

PMID- 25059073
TI  - [Medicine in early modern Japan and intercultural exchange].

PMID- 25059074
TI  - [I. The chagrin of Japanese medical officers in World War II].

PMID- 25059075
TI  - [II. Current and future issues in medical education in Japan: the relationship
      between the history of medicine and medical education].

PMID- 25059076
TI  - [Japanese preventive inoculation started in Akizuki-han in Fukuoka].

PMID- 25059077
TI  - Atypical development of configural face recognition in children with autism, Down
      syndrome and Williams syndrome.
AB  - BACKGROUND: Configural processing in face recognition is a sensitivity to the
      spacing between facial features. It has been argued both that its presence
      represents a high level of expertise in face recognition, and also that it is a
      developmentally vulnerable process. METHOD: We report a cross-syndrome
      investigation of the development of configural face recognition in school-aged
      children with autism, Down syndrome and Williams syndrome compared with a
      typically developing comparison group. Cross-sectional trajectory analyses were
      used to compare configural and featural face recognition utilising the 'Jane
      faces' task. Trajectories were constructed linking featural and configural
      performance either to chronological age or to different measures of mental age
      (receptive vocabulary, visuospatial construction), as well as the Benton face
      recognition task. RESULTS: An emergent inversion effect across age for detecting
      configural but not featural changes in faces was established as the marker of
      typical development. Children from clinical groups displayed atypical profiles
      that differed across all groups. CONCLUSION: We discuss the implications for the
      nature of face processing within the respective developmental disorders, and how
      the cross-sectional syndrome comparison informs the constraints that shape the
      typical development of face recognition.

PMID- 25059078
TI  - High prevalence of circulating autoantibodies against thyroid hormones in
      vitiligo and correlation with clinical and historical parameters of patients.
AB  - BACKGROUND: Autoantibodies against thyroid hormones (THAbs) directed towards
      triiodothyronine (T3-Ab) and/or thyroxine (T4-Ab) are very rare in the general
      population. They are increased in some nonthyroidal autoimmune diseases, where
      they seem to predict autoimmune thyroid disorders (ATDs). So far, their presence
      in patients with vitiligo has not been evaluated, but it might have a possible
      predictive role. OBJECTIVES: To assess the prevalence of THAbs in a group of
      vitiligo patients and to correlate their presence with clinical and historical
      parameters. METHODS: In total 79 patients with nonsegmental vitiligo and 100
      controls were examined. Clinical characteristics of vitiligo and family and
      personal medical history were evaluated. Antinuclear autoantibodies, thyroid
      hormones and thyroid autoantibodies were measured. IgM T3-Ab, IgG T3-Ab, IgM T4
      Ab and IgG T4-Ab were assayed by a radioimmunoprecipitation technique. Fisher's
      test, Student's t-test and chi(2)-test were used for statistical analysis.
      RESULTS: Overall 77 of 79 patients (97%) had at least one type of THAb (11 T3-Ab,
      10 T4-Ab, 56 both). In the control group, only one person (1%) had THAbs. In
      patients with vitiligo, T3-Abs were significantly associated with leucotrichia
      (IgM+IgG, P = 0.033; IgG, P = 0.039; IgM, P = 0.005) and thyroglobulin
      autoantibodies (IgM+IgG, P = 0.031; IgG, P = 0.058), while the absence of T3-Ab
      was related to personal history of cancer (IgM+IgG, P = 0.021; IgG, P = 0.039).
      T4-Abs were significantly associated with vitiligo activity (IgM+IgG, P < 0.001;
      IgM, P = 0.037) and duration (IgG, P = 0.013). CONCLUSIONS: The surprisingly high
      prevalence of THAb in patients with vitiligo and their associations suggest a
      possible pathogenetic role in the disease and stress the tight link between
      vitiligo and ATDs. Further evaluation in a larger group of patients and an
      adequate follow-up are needed to define their potential predictive role.

PMID- 25059079
TI  - Research is every nurse's business.

PMID- 25059080
TI  - Originality in doctoral research.

PMID- 25059081
TI  - What does originality in research mean? A student's perspective.
AB  - AIM: To provide a student's perspective of what it means to be original when
      undertaking a PhD. BACKGROUND: A review of the literature related to the concept
      of originality in doctoral research highlights the subjective nature of the
      concept in academia. Although there is much literature that explores the issues
      concerning examiners' views of originality, there is little on students'
      perspectives. REVIEW METHODS: A snowballing technique was used, where a recent
      article was read, and the references cited were then explored. Given the time
      constraints, the author recognises that the literature review was not as
      extensive as a systematic literature review. DISCUSSION: It is important for
      students to be clear about what is required to achieve a PhD. However, the
      vagaries associated with the formal assessment of the doctoral thesis and
      subsequent performance at viva can cause considerable uncertainty and anxiety for
      students. CONCLUSION: Originality in the PhD is a subjective concept and is not
      the only consideration for examiners. Of comparable importance is the assessment
      of the student's ability to demonstrate independence of thought and increasing
      maturity so they can become independent researchers. IMPLICATIONS FOR
      RESEARCH/PRACTICE: This article expresses a different perspective on what is
      meant when undertaking a PhD in terms of originality in the doctoral thesis. It
      is intended to help guide and reassure current and potential PhD students.

PMID- 25059082
TI  - Ethics and originality in doctoral research in the UK.
AB  - AIM: To show that the ethics governance process in the UK is not necessarily
      conducive to innovative investigation by doctoral students. BACKGROUND: Doctoral
      students need to demonstrate an original contribution to knowledge. This paper
      critically evaluates the concept of knowledge in relation to the concept of
      research paradigms. The purpose of this is to situate different claims to
      originality and show that original knowledge in nursing is always ethical
      knowledge of nursing. DATA SOURCES: Academic databases, local and national policy
      documents. REVIEW METHODS: Ethics governance procedures in nurse research in the
      UK are summarised. These are contrasted with ethical issues embedded in day-to
      day nursing practice. DISCUSSION: The author's argument is that current methods
      of ethics governance for doctoral research in the UK can be detrimental to the
      construction of original knowledge in nursing. This is because original research
      in nursing necessarily affects the ethics of care, but the gatekeeping function
      of risk-averse ethics committees tends to prevent students attempting ethically
      complex studies. This means less important research gets carried out. CONCLUSION:
      To mitigate these issues, doctoral students need to develop a solid understanding
      of the ethics governance process. They need to build relationships with relevant
      ethics committees. University ethics committees are ideally placed to help with
      this process. IMPLICATIONS FOR RESEARCH/PRACTICE: Without original research
      practice will remain reactive. Originality entails risk on the part of both
      researcher and ethics committee. Positive risk taking is more feasible in the
      context of collaboration and mutual understanding. Nurses should become more
      active in research governance.

PMID- 25059083
TI  - Using Facebook and participant information clips to recruit emergency nurses for
      research.
AB  - AIM: To examine the use of social networking sites in recruiting research
      participants. BACKGROUND: Workplace violence is an important issue for staff and
      patients. One workplace that reports the highest levels of violence is the
      emergency department. The ability to research issues such as workplace violence
      in real time is important in addressing them expeditiously, and social media can
      be used to advertise and recruit research subjects, implement studies and
      disseminate information. REVIEW METHODS: The experience of recruiting subjects
      through social networks, specifically Facebook, and the use of participant
      information clips (PICs) for advertising. DISCUSSION: A brief discussion of the
      history of advertising and communication using the internet is presented to
      provide an understanding of the trajectory of social media and implications for
      recruitment in general. The paper then focuses on the lead author's experience of
      recruiting subjects using Facebook, including its limitations and advantages, and
      her experience of using participant information clips. The low cost of
      advertising and recruiting participants this way, as well as the convenience
      provided to participants, resulted in almost half the study's total participants
      being obtained within 72 hours. CONCLUSION: Using Facebook to target a younger
      age range of nurses to participate in a study was successful and yielded a large
      number of completed responses in a short time period at little cost to the
      researcher. Recording the PIC was cheap, and posting it and a link to the site on
      pre-existing group pages was free, providing valuable viral marketing and
      snowball recruiting. IMPLICATIONS FOR RESEARCH/PRACTICE: Future researchers
      should not overlook using social network sites for recruitment if the
      demographics of the desired study population and subject matter permit it.

PMID- 25059084
TI  - Reaching a consensus on service-user involvement in courses for professionals.
AB  - AIM: To describe how a workshop that used a modified nominal group technique
      (NGT) was used at the end of a research project to develop a standard of
      education and training requiring UK education providers to include service users
      in the design and delivery of education and training. BACKGROUND: Often the
      objective of a research project is to deliver a decision where there is
      insufficient objective evidence. In this particular instance a decision was
      sought on whether service users should be involved in the design and delivery of
      education and training for healthcare professionals and what this involvement
      might look like. One solution can be to use a formal approach to decision making.
      NGT is one of several approaches to decision making that seeks to achieve
      consensus among participants. DATA SOURCES: A modified NGT workshop was used and
      included students, service users and academic staff. DISCUSSION: This paper
      describes the workshop, its outcomes and points to consider when using such an
      approach. CONCLUSION: This paper outlines a modified NGT that was used in a
      workshop to complement other research techniques and provides practical tips on
      how to maximise the chances of the success of the approach. Modifications were
      necessary to address the particular challenges posed in this research.
      IMPLICATIONS FOR RESEARCH/PRACTICE: The modified NGT approach outlined in this
      paper could be used by nurses when addressing questions and issues related to
      service-user involvement in planning the design and delivery of education and
      training.

PMID- 25059085
TI  - Being a practitioner: an application of Heidegger's phenomenology.
AB  - AIM: To explain how Heidegger's phenomenology can be applied to investigations of
      practitioners' experiences and enhance research of roles. BACKGROUND: The
      application of phenomenology in nursing research has been subject to strong
      criticism. A recent phenomenological investigation of nurses' experiences of
      mentoring students has shown the value of applying Heidegger's ideas to
      understand practitioners' experiences. DATA SOURCES: The author's experience of
      conducting a hermeneutic phenomenological study and influential literature.
      REVIEW METHODS: An inquiry into the author's application of Heidegger's
      philosophy to an empirical study. DISCUSSION: Heidegger's phenomenology was based
      on his concept of 'dasein', denoting existence as 'being in the world'. These
      ideas of existence are discussed in relation to the experiences of practitioners.
      A nurse or other practitioner's experiences of practice are explained according
      to three modes of being: absorbed in practice, noticing practice and
      contemplating practice. The paper shows how this layered understanding of a
      person's lifeworld can be incorporated into the design of empirical research.
      CONCLUSION: Heideggerian phenomenology provides a defendable framework in which
      to examine experience of practice. IMPLICATIONS FOR PRACTICE/RESEARCH: Given the
      expanding diversity of nursing roles, this methodology offers a route for
      improving our understanding of the implications for the nurses occupying
      particular roles.

PMID- 25059086
TI  - Use of theoretical and conceptual frameworks in qualitative research.
AB  - AIM: To debate the definition and use of theoretical and conceptual frameworks in
      qualitative research. BACKGROUND: There is a paucity of literature to help the
      novice researcher to understand what theoretical and conceptual frameworks are
      and how they should be used. This paper acknowledges the interchangeable usage of
      these terms and researchers' confusion about the differences between the two. It
      discusses how researchers have used theoretical and conceptual frameworks and the
      notion of conceptual models. Detail is given about how one researcher
      incorporated a conceptual framework throughout a research project, the purpose
      for doing so and how this led to a resultant conceptual model. REVIEW METHODS:
      Concepts from Abbott (1988) and Witz ( 1992 ) were used to provide a framework
      for research involving two case study sites. The framework was used to determine
      research questions and give direction to interviews and discussions to focus the
      research. DISCUSSION: Some research methods do not overtly use a theoretical
      framework or conceptual framework in their design, but this is implicit and
      underpins the method design, for example in grounded theory. Other qualitative
      methods use one or the other to frame the design of a research project or to
      explain the outcomes. An example is given of how a conceptual framework was used
      throughout a research project. CONCLUSION: Theoretical and conceptual frameworks
      are terms that are regularly used in research but rarely explained. Textbooks
      should discuss what they are and how they can be used, so novice researchers
      understand how they can help with research design. IMPLICATIONS FOR
      PRACTICE/RESEARCH: Theoretical and conceptual frameworks need to be more clearly
      understood by researchers and correct terminology used to ensure clarity for
      novice researchers.

PMID- 25059088
TI  - A view from Spain.

PMID- 25059087
TI  - A clash of paradigms? Western and indigenous views on health research involving
      Aboriginal peoples.
AB  - AIM: To explore the issues of data management and data ownership with regard to
      health research conducted in aboriginal or indigenous populations in Canada.
      BACKGROUND: Research with aboriginal communities in Canada has often been
      conducted by researchers who had little or no understanding of the community in
      which the research was taking place. This led to 'helicopter' research, which
      benefitted the researcher but not the community. National aboriginal leadership
      developed the ownership, control, access, and possession (OCAP) principles, which
      outline how to manage research data regarding aboriginal people and to counteract
      disrespectful methodologies. However, these principles present their own set of
      challenges to those who would conduct research with aboriginal populations. DATA
      SOURCES: Documents from the Assembly of First Nations, the Government of Canada,
      Aboriginal writers and researchers, and Nursing theorists and researchers. REVIEW
      METHODS: This is a methodology paper that reviews the issues of data ownership
      when conducting research with Aboriginal populations. DISCUSSION: The authors
      explore indigenous and Western views of knowledge development, outline and
      discuss the OCAP principles, and present the Canadian Institute of Health
      Research's guidelines for health research involving aboriginal people as a guide
      for those who want to carry out ethical and culturally competent research, do no
      harm and produce research that can benefit aboriginal peoples. CONCLUSION: There
      are special considerations associated with conducting research with Aboriginal
      populations. The Assembly of First Nations wants researchers to use the
      Ownership, Control, Access and Possession (OCAP) principles with First Nations
      data. These principles are restrictive and need to be discussed with stakeholders
      before research is undertaken. IMPLICATIONS FOR PRACTICE/RESEARCH: In Canada, it
      is imperative that researchers use the Canadian Institute of Health Research
      Guidelines for Health Research Involving Aboriginal People to ensure culturally
      sensitive and ethical conduct during the course of the research with Aboriginal
      populations. However, some communities may also want to use the OCAP principles
      and these principles will need to be taken into consideration when designing the
      study.

PMID- 25059093
TI  - Anxiety and locomotion in Genetic Absence Epilepsy Rats from Strasbourg (GAERS):
      inclusion of Wistar rats as a second control.
AB  - OBJECTIVE: The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a genetic
      model, derived from Wistar rats by selective breeding. In all previous studies,
      GAERS were compared to their paired selected strain not expressing spike-and-wave
      discharges (SWDs), namely nonepileptic controls (NECs). Because the
      occurrence/absence of SWDs is of polygenic origin, some other traits could have
      been selected along with occurrence/absence of SWDs. Therefore, we explored the
      importance of using a second control group consisting in Wistar rats, the strain
      of origin of GAERS, in addition to NECs, on locomotion and anxiety in GAERS.
      METHODS: A test battery encompassing home-cage, open-field, beam-walking and
      elevated plus-maze evaluations was used. In addition, stereologic analyses were
      performed to assess the volume of thalamus, amygdala, and hippocampus. The
      occurrence/absence of SWDs was determined in all three strains by
      electroencephalography (EEG) recording. RESULTS: When compared to NECs and
      Wistars, GAERS displayed lower exploratory activity and fastened habituation to
      novelty. In the plus-maze, scores of GAERS and Wistars were similar, but NECs
      appeared significantly less anxious (possibly in association with increased
      amygdala volume); evidence for weaker anxiety in NECs was also found in the open
      field evaluation. The volumetric study revealed increased thalamic volume in
      GAERS compared to both control groups. SWDs were present in all GAERS and in 80%
      of Wistars. SIGNIFICANCE: Compared to the original Wistar strain as an additional
      control group, the selective breeding that generated the GAERS has no incidence
      on anxiety-related behavior, conversely to the selection of SWD suppression in
      NECs, in which anxiety is attenuated. These findings point to the importance of
      using a second control group composed of Wistar rats in studies characterizing
      the behavioral profile of GAERS. Thereby, possible confusions between
      occurrence/absence of SWDs and other features that come along with selection
      and/or differential brain development induced by the genetic mutations are
      reduced.

PMID- 25059094
TI  - Sexual bother in men with advanced prostate cancer undergoing androgen
      deprivation therapy.
AB  - INTRODUCTION: Men with advanced prostate cancer (APC) undergoing androgen
      deprivation therapy (ADT) often experience distressing sexual side effects.
      Sexual bother is an important component of adjustment. Factors associated with
      increased bother are not well understood. AIMS: This study sought to describe
      sexual dysfunction and bother in APC patients undergoing ADT, identify socio
      demographic and health/disease-related characteristics related to sexual bother,
      and evaluate associations between sexual bother and psychosocial well-being and
      quality of life (QOL). METHODS: Baseline data of a larger psychosocial
      intervention study was used. Pearson's correlation and independent samples t-test
      tested bivariate relations. Multivariate regression analysis evaluated relations
      between sexual bother and psychosocial and QOL outcomes. MAIN OUTCOME MEASURES:
      The Expanded Prostate Cancer Index Composite sexual function and bother
      subscales, Center for Epidemiologic Studies Depression Scale, Functional
      Assessment of Cancer Therapy--General, and Dyadic Adjustment Scale were the main
      outcome measures. RESULTS: Participants (N = 80) were 70 years old (standard
      deviation [SD] = 9.6) and reported 18.7 months (SD = 17.3) of ADT. Sexual
      dysfunction (mean = 10.1; SD = 18.0) was highly prevalent. Greater sexual bother
      (lower scores) was related to younger age (beta = 0.25, P = 0.03) and fewer
      months of ADT (beta = 0.22, P = 0.05). Controlling for age, months of ADT,
      current and precancer sexual function, sexual bother correlated with more
      depressive symptoms (beta = -0.24, P  = 0.06) and lower QOL (beta = 0.25, P =
      0.05). Contrary to hypotheses, greater sexual bother was related to greater
      dyadic satisfaction (beta = -0.35, P = 0.03) and cohesion (beta = -0.42, P =
      0.01). CONCLUSIONS: The majority of APC patients undergoing ADT will experience
      sexual dysfunction, but there is variability in their degree of sexual bother.
      Psychosocial aspects of sexual functioning should be considered when evaluating
      men's adjustment to ADT effects. Assessment of sexual bother may help identify
      men at risk for more general distress and lowered QOL. Psychosocial interventions
      targeting sexual bother may complement medical treatments for sexual dysfunction
      and be clinically relevant, particularly for younger men and those first starting
      ADT.

PMID- 25059095
TI  - Arctic mutant Abeta40 aggregates on alpha7 nicotinic acetylcholine receptors and
      inhibits their functions.
AB  - Amyloid beta protein (Abeta) plays a central role in the pathogenesis of
      Alzheimer's disease (AD). Point mutations within the Abeta sequence associated
      with familial AD (FAD) are clustered around the central hydrophobic core of
      Abeta. Several types of mutations within the Abeta sequence have been identified,
      and the 'Arctic' mutation (E22G) has a purely cognitive phenotype typical of AD.
      Previous studies have shown that the primary result of the 'Arctic' mutation is
      increased formation of Abeta protofibrils. However, the molecular mechanism
      underlying this effect remains unknown. Abeta42 binds to a neuronal nicotinic
      acetylcholine receptor subunit, neuronal acetylcholine receptor subunit alpha-7
      (CHRNA7), with high affinity and, thus, may be involved in the pathogenesis of
      AD. Therefore, to clarify the molecular mechanism of Arctic mutation-mediated
      FAD, we focused on CHRNA7 as a target molecule of Arctic Abeta. We performed an
      in vitro binding assay using purified CHRNA7 and synthetic Arctic Abeta40, and
      demonstrated that Arctic Abeta40 specifically bound to CHRNA7. The aggregation of
      Arctic Abeta40 was enhanced with the addition of CHRNA7. Furthermore, the
      function of CHRNA7 was detected by measuring Ca(2+) flux and phospho-p44/42 MAPK
      (ERK1/2) activation. Our results indicated that Arctic Abeta40 aggregation was
      enhanced by the addition of CHRNA7, which destabilized the function of CHRNA7 via
      inhibition of Ca(2+) responses and activation of ERK1/2. These findings indicate
      that Arctic Abeta mutation may be involved in the mechanism underlying FAD. This
      mechanism may involve binding and aggregation, leading to the inhibition of
      CHRNA7 functions.

PMID- 25059096
TI  - Reinsertion of the gastric coronary vein to avoid venous gastric congestion in
      pancreatic surgery.

PMID- 25059097
TI  - Selective increase of in vivo firing frequencies in DA SN neurons after
      proteasome inhibition in the ventral midbrain.
AB  - The impairment of protein degradation via the ubiquitin-proteasome system (UPS)
      is present in sporadic Parkinson's disease (PD), and might play a key role in
      selective degeneration of vulnerable dopamine (DA) neurons in the substantia
      nigra pars compacta (SN). Further evidence for a causal role of dysfunctional UPS
      in familial PD comes from mutations in parkin, which results in a loss of
      function of an E3-ubiquitin-ligase. In a mouse model, genetic inactivation of an
      essential component of the 26S proteasome lead to widespread neuronal
      degeneration including DA midbrain neurons and the formation of alpha-synuclein
      positive inclusion bodies, another hallmark of PD. Studies using pharmacological
      UPS inhibition in vivo had more mixed results, varying from extensive
      degeneration to no loss of DA SN neurons. However, it is currently unknown
      whether UPS impairment will affect the neurophysiological functions of DA
      midbrain neurons. To answer this question, we infused a selective proteasome
      inhibitor into the ventral midbrain in vivo and recorded single DA midbrain
      neurons 2 weeks after the proteasome challenge. We found a selective increase in
      the mean in vivo firing frequencies of identified DA SN neurons in anesthetized
      mice, while those in the ventral tegmental area (VTA) were unaffected. Our
      results demonstrate that a single-hit UPS inhibition is sufficient to induce a
      stable and selective hyperexcitability phenotype in surviving DA SN neurons in
      vivo. This might imply that UPS dysfunction sensitizes DA SN neurons by enhancing
      'stressful pacemaking'.

PMID- 25059098
TI  - The role of microRNA-15b in the impaired angiogenesis in diabetic wounds.
AB  - The impairment in diabetic wound healing represents a significant clinical
      problem. Decreased angiogenesis is thought to play a central role in the
      pathogenesis of this impairment. We have previously shown that treatment of
      diabetic murine wounds with mesenchymal stem cells can improve healing, but the
      mechanisms are not completely defined. MicroRNA-15b (miR-15b) has been implicated
      in the regulation of the angiogenic response. We hypothesized that abnormal miR
      15b expression may contribute to the impaired angiogenesis observed in impaired
      diabetic wound healing. To test this hypothesis, we examined the expression of
      miR-15b and its target genes in diabetic and nondiabetic mice before and after
      injury. MiR-15b expression was significantly up-regulated in diabetic mouse
      wounds during the wound healing response. Increased miR-15b levels also closely
      correlated with decreased gene expression of its proangiogenic target genes.
      Furthermore, the correction of the diabetic wound healing impairment with
      mesenchymal stem cell treatment was associated with a significant decrease in miR
      15b expression level and increased gene expression of its proangiogenic target
      genes. These results provide the first evidence that increased expression of miR
      15b in diabetic wounds in response to injury may, in part, be responsible for the
      abnormal angiogenic response seen in diabetic wounds and may contribute to the
      observed wound healing impairment. 

PMID- 25059099
TI  - Updated NICE guideline: management of atrial fibrillation (2014).
AB  - There is significant progress made in the field of atrial fibrillation,
      especially regarding stroke stratification, novel pharmacological agents and
      interventions for improving symptom control. The Updated NICE Guideline for
      management of 2014 reflects that and provided an up-to-date appraisal regarding
      atrial fibrillation treatment, management with consideration to overall
      healthcare cost economics. It emphasizes the need for individualized, patient
      centered package of care, and an robust stroke and bleeding risk before decision
      regarding choice of oral anticoagulation to be made. 

PMID- 25059100
TI  - Endocyclic oxygen in 3-fluorodihydro-2H-pyran-4(3H)-one that does not induce the
      gauche effect.
AB  - 2-Fluorocyclohexanone undergoes chair inversion, giving rise to axial and
      equatorial conformers, with the equatorial form being highly preferred in
      solution, for example, 87% in chloroform and 93% in methylene chloride.
      Modifications in the conformational preferences can modify macroscopic properties
      of 2-fluoro ketones. The introduction of an endocyclic oxygen in 2
      fluorocyclohexanone to give 3-fluorodihydro-2H-pyran-4(3H)-one would be expected
      to create a gauche effect in the axial conformer along with the O-C-C-F moiety,
      inducing an increase of its population. However, small changes were verified in
      the conformational populations both in the gas phase and solution because the
      carbonyl group plays an important role for the hyperconjugation in the equatorial
      conformer, despite experiencing strong dipolar repulsion with the fluorine atom.
      These data were obtained theoretically and by NMR spectroscopy, while the nature
      of the interactions governing these conformational shifts were investigated on
      the basis of natural bond orbital analysis. 

PMID- 25059101
TI  - Higher risk of orofacial clefts in children born to mothers with angina pectoris:
      a population-based case-control study.
AB  - Previously an unexpected association of maternal angina pectoris (MAP) during
      pregnancy with a higher risk of orofacial clefts in their children was found.
      There were three objectives of this study: (i) to evaluate the validity of MAP
      diagnoses in the previous study and the recent history of mothers with MAP in a
      follow-up study; (ii) to estimate the prevalence of other congenital
      abnormalities in the offspring of mothers with MAP; and (iii) to analyze the
      possible effect of confounders for the risk of orofacial clefts. The large
      dataset of population-based Hungarian Case-Control Surveillance System of
      Congenital Abnormalities, 1980-1996 was evaluated including 22 843 cases with
      congenital abnormalities and 38 151 controls without any defect. Twenty-two cases
      (0.10%) and 12 controls (0.03%) were born to mothers with medically recorded MAP
      (odds ratio [OR] with 95% confidence interval [CI]: 3.7, 1.8-7.3). Of 22 cases,
      six had isolated cleft lip +/- palate (OR with 95% CI: 13.3, 4.9-35.9) and two
      were affected with isolated cleft palate (OR with 95% CI: 10.5, 2.3-47.6). The
      diagnosis of MAP was confirmed in seven women visited at home in 2009-2010, two
      had recent myocardial infarction and five were smokers. There was no higher risk
      for other congenital abnormalities. In conclusion the higher risk of orofacial
      clefts was confirmed in the children of mothers with MAP and smoking may trigger
      the genetic predisposition of both MAP and orofacial clefts. However, the number
      of cases was limited and therefore further studies are needed to confirm or
      reject this theoretically and practically important observation. 

PMID- 25059103
TI  - Mechanical circulatory assist as a bridge to heart retransplantation in
      adolescents.
AB  - We report our experience with an adolescent patient who required complex
      management leading to retransplantation for coronary allograft vasculopathy and
      also review the role of ventricular assist device support in patients with this
      clinical entity.

PMID- 25059102
TI  - Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses
      against human B cell malignancies in mice.
AB  - BACKGROUND: Therapeutic idiotypic (Id) vaccination is an experimental treatment
      for selected B cell malignancies. A broader use of Id-based vaccination, however,
      is hampered by the complexity and costs due to the individualized production of
      protein vaccines. These limitations may be overcome by targeted DNA vaccines
      encoding stereotyped immunoglobulin V regions of B cell malignancies. We have
      here investigated whether such vaccines might elicit cross-reactive immune
      responses thus offering the possibility to immunize subsets of patients with the
      same vaccine. METHODS: Fusion vaccines targeting patient Id to mouse Major
      Histocompatibility Complex (MHC) class II molecules (chimeric mouse/human) or
      chemokine receptors (fully human) on antigen-presenting cells (APC) were
      genetically constructed for two Chronic Lymphocytic Leukemia (CLL) patients and
      one prototypic stereotyped B-cell receptor (BCR) commonly expressed by Hepatitis
      C Virus (HCV)-associated Non Hodgkin Lymphoma (NHL). The A20 murine B lymphoma
      cells were engineered to express prototypic HCV-associated B cell lymphoma BCR.
      Anti-Id antibody responses were studied against stereotyped and non-stereotyped
      BCRs on CLL patients' cells as well as transfected A20 cells. RESULTS: DNA
      vaccination of mice with Id vaccines that target APC elicited increased amounts
      of antibodies specific for the patient's Id as compared with non targeted control
      vaccines. Anti-Id antibodies cross-reacted between CLL cells with closely related
      BCR. A20 cells engineered to express patients' V regions were not tumorigenic in
      mice, preventing tumor challenge experiments. CONCLUSIONS: These findings provide
      experimental support for use of APC-targeted fusion Id DNA vaccines for the
      treatment of B cell lymphoma and CLL that express stereotyped BCRs.

PMID- 25059104
TI  - Delirium among critically ill adults: evaluation of the psychometric properties
      of the Italian 'Confusion Assessment Method for the Intensive Care Unit'.
AB  - OBJECTIVES: To determine the psychometric properties of the Italian version of
      the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), a clinical
      assessment tool to detect delirium among Intensive Care Unit patients. DESIGN:
      Validation study. RESEARCH METHODOLOGY: Fifty-seven patients admitted to three
      medical and surgical Intensive Care Units were recruited. During the study
      interval two trained examiners performed independent delirium assessment by the
      CAM-ICU for a maximum of four times per patient. MAIN OUTCOME MEASURES:
      Interrater reliability and internal consistency of the tool, which were measured
      using Cohen's kappa and Cronbach's alpha coefficients respectively. FINDINGS:
      Seventy-two paired evaluations were collected. The 35% of the studied cohort
      tested positive for delirium. The Italian version of the CAM-ICU demonstrated a
      substantial interrater reliability (kappa=0.76, p<0.0001) and a very good
      internal consistency (alpha=0.87, 95% confidence interval: 0.81-0.91).
      CONCLUSION: The Italian CAM-ICU was found to be a viable instrument by which to
      approach a standardised monitoring of delirium among Italian speaking ICU
      patients. The use of such tools may facilitate ICU physicians and nurses in
      detecting delirium, thus improving both quality and safety of care.

PMID- 25059105
TI  - Team competence among nurses in an intensive care unit: the feasibility of in
      situ simulation and assessing non-technical skills.
AB  - OBJECTIVES: Nursing competence affects quality of care in intensive care units
      (ICUs). Team competence is particularly important for preventing errors. This
      paper focuses on the feasibility of using an in situ simulation model to explore
      team competence in the ICU, and on using parts of the Anaesthetists' Non
      Technical Skills (ANTS) taxonomy for assessing Non-Technical Skills (NTS) in
      nursing teams. METHODOLOGY/DESIGN: Seventy-two nurses were randomised into two
      groups and introduced to a new guideline via either lecture-based or simulation
      based teaching. A preprogrammed patient simulator and a video camera were
      installed inside the ICU, and a scenario was enacted to simulate the admission of
      a patient with septic shock. All available facilities in the ICU were used. Two
      blinded raters evaluated "Team Working" and "Situation Awareness" via video
      recordings using the ANTS taxonomy. RESULTS: Due to high activity in the ICU, 54
      nurses completed the in situ simulation. Assessments of the video recordings
      revealed moderate agreement between the two raters. Observations revealed issues
      deviating from expected standards of competence. CONCLUSION: In situ simulation
      may be feasible for assessing competence in ICUs. The ANTS appears to be a
      promising foundation for developing a team assessment tool for ICUs.

PMID- 25059106
TI  - Intracystic interferon therapy in childhood craniopharyngioma: who, when and how?
AB  - A 13-year-old male presents with fluctuating visual disturbance and headaches.
      Imaging reveals a significant predominantly cystic suprasellar tumour, typical of
      a craniopharyngioma. The patient has growth hormone deficiency but the rest of
      the hypothalamic/pituitary axis is intact. What are the options for therapy in
      2014? Specifically, is there a role for local treatment with interferon injected
      into the cyst cavity? The aim of management in children with craniopharyngiomas
      is to reduce the impact of the tumour as much as possible, while minimising the
      morbidity associated with treatment. There are a number of therapeutic options
      available: surgery, radiotherapy and the insertion of therapeutic agents directly
      into the tumour cyst. The role of intracystic therapy in the form of interferon
      is discussed; including when to use this therapeutic option and practical details
      of its use. 

PMID- 25059107
TI  - Mutations in tubulin genes are frequent causes of various foetal malformations of
      cortical development including microlissencephaly.
AB  - Complex cortical malformations associated with mutations in tubulin genes are
      commonly referred to as "Tubulinopathies". To further characterize the mutation
      frequency and phenotypes associated with tubulin mutations, we studied a cohort
      of 60 foetal cases. Twenty-six tubulin mutations were identified, of which TUBA1A
      mutations were the most prevalent (19 cases), followed by TUBB2B (6 cases) and
      TUBB3 (one case). Three subtypes clearly emerged. The most frequent (n = 13) was
      microlissencephaly with corpus callosum agenesis, severely hypoplastic brainstem
      and cerebellum. The cortical plate was either absent (6/13), with a 2-3 layered
      pattern (5/13) or less frequently thickened (2/13), often associated with
      neuroglial overmigration (4/13). All cases had voluminous germinal zones and
      ganglionic eminences. The second subtype was lissencephaly (n = 7), either
      classical (4/7) or associated with cerebellar hypoplasia (3/7) with corpus
      callosum agenesis (6/7). All foetuses with lissencephaly and cerebellar
      hypoplasia carried distinct TUBA1A mutations, while those with classical
      lissencephaly harbored recurrent mutations in TUBA1A (3 cases) or TUBB2B (1
      case). The third group was polymicrogyria-like cortical dysplasia (n = 6),
      consisting of asymmetric multifocal or generalized polymicrogyria with inconstant
      corpus callosum agenesis (4/6) and hypoplastic brainstem and cerebellum (3/6).
      Polymicrogyria was either unlayered or 4-layered with neuronal heterotopias (5/6)
      and occasional focal neuroglial overmigration (2/6). Three had TUBA1A mutations
      and 3 TUBB2B mutations. Foetal TUBA1A tubulinopathies most often consist in
      microlissencephaly or classical lissencephaly with corpus callosum agenesis, but
      polymicrogyria may also occur. Conversely, TUBB2B mutations are responsible for
      either polymicrogyria (4/6) or microlissencephaly (2/6). 

PMID- 25059109
TI  - Sociocultural risk factors for compulsive exercise: a prospective study of
      adolescents.
AB  - The risk factors for compulsive exercise are unknown. This study aims to explore
      longitudinal sociocultural risk factors for compulsive exercise, using a 12-month
      prospective design. A sample of 332 male and female adolescents (aged 13-15 years
      at baseline) completed self-report measures of sociocultural risk factors and
      compulsive exercise at baseline and eating disorder psychopathology and
      compulsive exercise at 12-month follow-up assessment. Hierarchical regressions
      found that family and peer messages to become more muscular predicted compulsive
      exercise in boys, whereas feeling pressure from the media to be thin was a
      significant predictor of compulsive exercise in girls. These relationships
      remained significant when controlling for eating disorder psychopathology but
      became nonsignificant when initial levels of compulsive exercise were entered
      into the model. The findings suggest that sociocultural risk factors may
      contribute to the development of compulsive exercise but future research should
      utilise a younger sample and employ a longer follow-up period to identify true
      longitudinal effects.

PMID- 25059110
TI  - Inhibition of NF-kappaB activation by diethylcarbamazine prevents alcohol-induced
      liver injury in C57BL/6 mice.
AB  - Induction of NF-kappaB-mediated gene expression has been identified in the
      pathogenesis of alcoholic liver disease (ALD). Diethylcarbamazine (DEC) is a
      piperazine derivative drug with anti-inflammatory properties. The present study
      was designed to evaluate the effect of DEC on NF-kappaB pathways in mice
      undergoing alcoholism induced hepatic inflammation. Forty male C57BL/6 mice were
      divided equally into four groups: control group (C); DEC-treated group, which
      received 50mg/kg (DEC50); alcoholic group (EtOH), submitted to chronic alcohol
      consumption and the alcohol-DEC treated group (EtOH50), submitted to chronic
      alcoholism consumption plus DEC treatment. Histological analysis of the alcoholic
      group showed evident hepatocellular damage which was reduced in EtOH50 group.
      Immunohistochemistry and western blot results showed elevated expression of
      inflammatory markers such as MDA, TNF-alpha, IL-1beta, COX-2 and iNOS in
      hepatocytes of EtOH group. However, low immunopositivity for these markers was
      detected following DEC treatment. In the EtOH group the activation of NF-kappaB
      was observed by an increase in the expression of both NF-kappaB and pNF-kappaB in
      hepatocytes. This expression was significantly reduced in livers of EtOH50 group.
      Protein expression of Ikappabetaalpha was measured to determine whether
      activation of NF-kappaB might be the result of Ikappabetaalpha degradation. It
      was observed that expression of this protein was low in EtOH group, while animals
      treated with DEC had a high expression of Ikappabetaalpha. The results of the
      present study indicate that DEC alleviates alcoholic liver injury, in part by the
      inhibiting activation of NF-kappaB and by suppressing the induction of NF-kappaB
      dependent genes.

PMID- 25059108
TI  - Metabolically healthy and unhealthy obese--the 2013 Stock Conference report.
AB  - Obesity is closely associated with cardiovascular diseases and type 2 diabetes,
      but some obese individuals, despite having excessive body fat, exhibit metabolic
      health that is comparable with that of lean individuals. The 'healthy obese'
      phenotype was described in the 1980s, but major advancements in its
      characterization were only made in the past five years. During this time, several
      new mechanisms that may be involved in health preservation in obesity were
      proposed through the use of transgenic animal models, use of sophisticated
      imaging techniques and in vivo measurements of insulin sensitivity. However, the
      main obstacle in advancing our understanding of the metabolically healthy obese
      phenotype and its related long-term health risks is the lack of a standardized
      definition. Here, we summarize the proceedings of the 13th Stock Conference of
      the International Association of the Study of Obesity. We describe the current
      research and highlight the unanswered questions and gaps in the field. Better
      understanding of metabolic health in obesity will assist in therapeutic decision
      making and help identify therapeutic targets to improve metabolic health in
      obesity. 

PMID- 25059111
TI  - Morphological, immunohistochemical and ultrastructural characterization of the
      skin of turbot (Psetta maxima L.).
AB  - This study was undertaken to identify the normal morphologic, immunohistochemical
      and ultrastructural features of skin of the turbot (Psetta maxima L.). In the
      turbot skin, three morphologically distinct layers were identified: epidermis,
      dermis and hypodermis. The epidermis was non-keratinizing, stratified squamous
      epithelium that varies in thickness from 5 to 14 cells and 60 to 100MUm in size.
      Goblet cells were seen randomly distributed between malpighian cells in the
      epidermal layer. These mucous cells were mainly located in the upper third of the
      epidermis and displayed a spherical to elongated morphology. Dermis was divided
      in two well-differentiated layers, the superficial stratum laxum and the deeper
      stratum compactum. Hypodermis was a loose layer mainly composed by adipocytes but
      we could observe variable amounts of fibroblast, collagen and blood vessels. In
      turbot two pigmentary layers could be identified: the pigmentary layer of dermis
      was located between basement membrane and dermis and the pigmentary layer of
      hypodermis immediately above the muscular layer. Three different types of
      chromatophores were present: melanophores, iridophores and xanthophores. The main
      differences observed between groups of fish with different colouration were in
      the amount of melanophores and xanthophores. The purpose of this article is to
      provide an overview of normal cutaneous biology prior to consideration of
      specific cutaneous alterations and diseases in turbot.

PMID- 25059112
TI  - Transcranial optical vascular imaging (TOVI) of cortical hemodynamics in mouse
      brain.
AB  - In vivo imaging of cerebral vasculature and blood flow provides highly valuable
      information for clinicians as well as researchers. Nevertheless, currently
      available methods are complex, time-consuming and expensive. Here, we present a
      novel, minimally invasive method for vascular imaging through the sufficiently
      transparent intact skull of young mice. Our method combines laser speckle and
      fluorescent imaging with dynamic color mapping and image fusion. Quickly
      generated wide-field images present clear visual information on blood flow and
      perfusion in the cerebral cortex and meninges. The ability of the method to
      visualize hemodynamic changes is demonstrated by induced occlusion of the middle
      cerebral artery. The compact and easily operated system comprises of several
      pieces of standard and affordable laboratory equipment. This simple, robust and
      inexpensive method may become an important tool for assessment of brain
      hemodynamics in preclinical studies. 

PMID- 25059113
TI  - Copper-promoted site-selective acyloxylation of unactivated C(sp3)-H bonds.
AB  - The site-selective acyloxylation of aliphatic amides was achieved via a copper
      promoted C(sp(3))-H bond functionalization process directed by a bidentate
      ligand. The reaction showed a great preference for activating C-H bonds of beta
      methyl groups over those of gamma-methyl and unactivated methylene groups.

PMID- 25059114
TI  - Directly utilizing an endogenous gene to dissect regulatory elements in the
      biosynthetic gene cluster of nosiheptide.
AB  - The regulatory elements for nosiheptide biosynthesis were identified by a novel
      host-vector system with an endogenous gene within the biosynthetic gene cluster
      as a reporter gene. The present study offers a rapid and reliable method for the
      identification of regulatory elements in the biosynthesis of various bioactive
      natural products. 

PMID- 25059115
TI  - Maternal pregravid body mass index and child hospital admissions in the first 5
      years of life: results from an Australian birth cohort.
AB  - OBJECTIVES: To examine the association of maternal pregravid body mass index
      (BMI) and child offspring, all-cause hospitalisations in the first 5 years of
      life. METHODS: Prospective birth cohort study. From 2006 to 2011, 2779 pregnant
      women (2807 children) were enrolled in the Environments for Healthy Living:
      Griffith birth cohort study in South-East Queensland, Australia. Hospital
      delivery record and self-report baseline survey of maternal, household and
      demographic factors during pregnancy were linked to the Queensland Hospital
      Admitted Patients Data Collection from 1 November 2006 to 30 June 2012, for child
      admissions. Maternal pregravid BMI was classified as underweight (<18.5 kg m(
      )(2)), normal weight (18.5-24.9 kg m(-)(2)), overweight (25.0-29.9 kg m(-)(2)) or
      obese (?30 kg m(-)(2)). Main outcomes were the total number of child hospital
      admissions and ICD-10-AM diagnostic groupings in the first 5 years of life.
      Negative binomial regression models were calculated, adjusting for follow-up
      duration, demographic and health factors. The cohort comprised 8397.9 person
      years (PYs) follow-up. RESULTS: Children of mothers who were classified as obese
      had an increased risk of all-cause hospital admissions in the first 5 years of
      life than the children of mothers with a normal BMI (adjusted rate ratio (RR)
      =1.48, 95% confidence interval 1.10-1.98). Conditions of the nervous system,
      infections, metabolic conditions, perinatal conditions, injuries and respiratory
      conditions were excessive, in both absolute and relative terms, for children of
      obese mothers, with RRs ranging from 1.3-4.0 (PYs adjusted). Children of mothers
      who were underweight were 1.8 times more likely to sustain an injury or poisoning
      than children of normal-weight mothers (PYs adjusted). CONCLUSION: RESULTS
      suggest that if the intergenerational impact of maternal obesity (and similarly
      issues related to underweight) could be addressed, a significant reduction in
      child health care use, costs and public health burden would be likely.

PMID- 25059116
TI  - Racial/ethnic differences in accuracy of body mass index reporting in a diverse
      cohort of young adults.
AB  - Surveillance data describing the weight status of the U.S. population often rely
      on self-reported height and weight, despite likely differences in reporting
      accuracy by demographics. Our objective was to determine if there were
      racial/ethnic differences in accuracy of self-reported body mass index (BMI) in a
      diverse nationally representative sample of young people. Using data from Wave
      III (data collected in 2001-2002) of the National Longitudinal Study of
      Adolescent Health when respondents were aged 18-26, we used gender-stratified
      multivariable linear regression models to examine the association of
      race/ethnicity and self-reported BMI controlling for measured BMI while also
      adjusting for factors known to be associated with weight self-perception. Black
      males and females (b(Female)=0.45, confidence interval (CI): 0.19, 0.71;
      b(Male)=0.34, CI: 0.17, 0.51) and Hispanic females (b(Female)=0.30, CI: 0.08,
      0.52) and Native American males (b(Native) American=0.87, CI: 0.15, 1.58)
      reported higher BMIs than their similarly weighted White peers, leading to more
      accurate BMI reporting in these groups at higher BMIs. Caution should be taken in
      interpreting results from studies relying on self-reported BMI, as they may
      exaggerate racial/ethnic differences in weight status.

PMID- 25059117
TI  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: report of seven
      additional sicilian patients and overview of the overall series from sicily.
AB  - BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) is a rare recessive inherited disease caused by the mutation of the AIRE
      gene on chromosome 21. To date, 8 Sicilian patients have been described and the
      R203X AIRE mutation was found to be the most common in this region. AIMS: (1) To
      describe 7 additional Sicilian APECED patients and to review all 15 Sicilian
      APECED patients who have been investigated by our group in the last years, and
      (2) to report a novel AIRE gene mutation. RESULTS: Among the 3 cardinal features
      of APECED, hypoparathyroidism has been already detected in all 15 patients,
      whereas Addison's disease and chronic mucocutaneous candidiasis have so far been
      found in 10/15 and 12/15 cases, respectively. In 2 consanguineous cases, AIRE
      gene analysis revealed a novel mutation, named IVS13+2T, in homozygosis. R203X
      was the most common mutation in this region (30% of alleles and 46.6% of
      patients), followed by R257X (20% of alleles and 40% of patients). CONCLUSIONS:
      Sicilian APECED patients are confirmed to have some peculiar characteristics from
      a clinical and genetic point of view. No correlations between genotype and
      phenotype were identified.

PMID- 25059119
TI  - A novel MVK missense mutation in one Chinese family with disseminated superficial
      actinic porokeratosis.
AB  - Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic
      autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate
      kinase, (MVK) a gene know to play an important role in regulation of calcium
      induced keratinocyte differentiation and proliferation, has recently been
      suggested as the disease-causing gene for DSAP. Here we report a direct
      sequencing analysis of this gene in 3 DSAP families, 6 sporadic cases, and 100
      unrelated healthy controls. We detected a heterozygous T to A transition at
      nucleotide 205 in exon 3 of MVK gene in one familial case. This mutation will
      result in an amino acid change at codon 69 (P.Ser69Thr), which is from a serine
      codon (TCA) to a threonine codon (ACA). No such mutation was detected in the
      unaffected family members or the 100 unrelated healthy controls. Our results
      demonstrated a novel missense mutation in MVK gene. This will be valuable for the
      diagnosis of DSAP as well as for genetic counseling and prenatal diagnosis of
      affected families. 

PMID- 25059118
TI  - Association between Fok I vitamin D receptor gene (VDR) polymorphism and
      impulsivity in alcohol-dependent patients.
AB  - Vitamin D appears to have an important role in the modulation of the central
      nervous system. Vitamin D exerts its biological effects through its interaction
      with the vitamin D receptor (VDR). Located on chromosome 12 (12q13.1), the VDR
      gene has many different polymorphisms. Some of them are known to affect the VDR
      function, such as FokI (rs2228570, T/C) single nucleotide polymorphism. We aimed
      to explore a potential relationship between FokI VDR polymorphism and
      impulsiveness in alcohol-dependent (AD) patients. The study population consisted
      of 148 patients diagnosed with alcohol dependence (DSM-IV criteria) and 212
      healthy controls. DNA was extracted from whole blood samples using the standard
      procedure. Genotypes were analyzed using a real-time PCR method. We found that
      FokI VDR gene polymorphism was associated with impulsivity [Barratt Impulsiveness
      Scale (BIS)-11 total score; P = 0.014], and with attentional impulsivity (BIS-11
      subscale; P = 0.002) in the male AD patients. Our results suggest that CC FokI
      genotype of the VDR gene is associated with a higher level of impulsivity in
      these patients. This finding supports the hypothesis that impulsiveness, which
      significantly contributes to development of alcohol dependence, has a genetic
      background. 

PMID- 25059120
TI  - Akt2 mediates TGF-beta1-induced epithelial to mesenchymal transition by
      deactivating GSK3beta/snail signaling pathway in renal tubular epithelial cells.
AB  - BACKGROUND: The epithelial-mesenchymal transition (EMT) induced by growth factors
      or cytokines, particularly transforming growth factor-beta (TGF-beta1), plays an
      important role in kidney tubulointerstitial injury. However, signaling pathways
      mediating TGF-beta1-induced EMT are not precisely known. In this study, we
      examined the role of Akt2 on EMT. METHODS: HK-2 cells were exposed to 10 ng/ml
      TGF-beta1 to establish a model of EMT. The expression of proteins were detected
      by western blot assay and Immunofluorescence. The levels of genes were tested by
      RT-PCR. RESULTS: We found that treatment of HK-2 cells, a human proximal tubular
      cell line, with 10 ng/ml TGF-beta1 resulted in activation of phosphatidylinositol
      3-kinase (PI3K)/Akt2 signaling as evidenced by increased p-PI3K, Akt2 and p-Akt
      (Ser 473) expression. Importantly, TGF-beta1 treatment decreased zona occludins 1
      (ZO-1) and E-cadherin (epithelial markers) expression, increased fibronectin and
      vimentin (mesenchymal makers) expression, which were prevented by Ly294002 (the
      inhibitor of PI3K) or small interfering RNA (siAkt2), suggesting that Akt2
      mediated TGF-beta1-induced EMT. Meanwhile, RNA and protein levels of Snail1, the
      key inducer of EMT, were significantly elevated in TGF-beta1-treated HK-2 cells.
      TGF-beta1 also induced inactivation of glycogen synthase kinase-3beta (GSK3beta),
      an endogenous inhibitor of Snail. Knockdown of Akt2 using siRNAs or the PI3K
      inhibitor Ly294002 inhibited TGF-beta1-induced phosphorylation of GSK3beta and
      expression of Snail1. CONCLUSION: These findings revealed that knockdown of Akt2
      antagonized TGF-beta1-induced EMT by inhibiting GSK3beta/Snail signaling pathway.

PMID- 25059122
TI  - A simple and sensitive vortex assisted liquid-liquid microextraction method for
      the simultaneous determination of haloanisoles and halophenols in wines.
AB  - A vortex assisted liquid-liquid microextraction (VALLME) method was developed and
      optimised for the determination of the main compounds that can cause cork taint
      in wines, 2,4,6-trichloroanisole (TCA), 2,3,4,6-tetrachloroanisole (TeCA), 2,4,6
      tribromoanisole (TBA) and pentachloroanisole (PCA); and their corresponding
      halophenolic precursors. Target compounds were determined by gas chromatography
      combined with a micro-electron capture detector (GC-uECD) system. Halophenol
      extraction and derivatisation processes were performed at the same time. To
      optimise the VALLME method, the extraction solvent was selected. Then, the other
      parameters of influence, such as volume of extraction solvent and derivatisation
      agent, salt addition and vortex time were optimised using a central composite
      design combined with desirability functions. Once the optimal conditions had been
      determined, the method was validated, showing satisfactory linearity (with
      correlation coefficients over 0.983), repeatability (below 10.0%) and
      reproducibility (below 11.2%). Detection limits obtained were lower than the
      olfactory threshold of the studied compounds, being similar or even lower than
      previously reported with the advantage of reducing the extraction time. The
      analysis of real wine samples demonstrated the applicability of the method. To
      our knowledge, this is the first time that VALLME has been applied for the
      simultaneous determination of haloanisoles and halophenols in wine.

PMID- 25059121
TI  - 'Red Ruby': an interactive web-based intervention for lifestyle modification on
      metabolic syndrome: a study protocol for a randomized controlled trial.
AB  - BACKGROUND: Although effectiveness of web-based interventions on lifestyle
      changes are recognized, the potential of such programs on metabolic syndrome has
      not been explored. We describe the protocol of a randomized controlled trial that
      aims to determine the feasibility, acceptability, usability, and effectiveness of
      interactive technology on lifestyle intervention in a population with metabolic
      syndrome. METHODS/DESIGN: This is a two-arm randomized controlled trial. The
      study includes 160 participants (n = 80 per arm) who will be recruited via online
      registration on the study website. The inclusion criteria are that they should
      have metabolic syndrome and have access to the Internet. All participants will
      receive information on dietary intake and physical activity through the study
      website. The intervention group will receive additional resources via the study
      website including interactive Healthy Heart Profile and calorie restricted diet
      tailored to the participants. The primary outcomes are feasibility,
      acceptability, usability, and the change in metabolic syndrome components. The
      secondary outcomes are comparing quality of life, physical activity and food
      intake among the study arms. The participants will be followed up to 6 months
      with data collection scheduled at baseline, 3 and 6 months. DISCUSSION: There is
      a need for developing and evaluating web-based interventions that target people
      with high risk for cardiovascular diseases. This study will therefore make an
      important contribution to this novel field of research and practice. TRIAL
      REGISTRATION: IRCT201111198132N1.

PMID- 25059123
TI  - A novel strategy for synthesis of hollow gold nanosphere and its application in
      electrogenerated chemiluminescence glucose biosensor.
AB  - Well-distributed hollow gold nanospheres (Aushell@GOD) (20 +/- 5 nm) were
      synthesized using the glucose oxidase (GOD) cross-linked with glutaraldehyde as a
      template. A glucose biosensor was prepared based on Aushell@GOD nanospheres for
      catalyzing luminol electrogenerated chemiluminescence (ECL). Firstly, chitosan
      was modified in a glassy carbon electrode which offered an interface of abundant
      amino-groups to assemble Aushell@GOD nanospheres. Then, glucose oxidase was
      adsorbed on the surface of Aushell@GOD nanospheres via binding interactions
      between Aushell and amino groups of GOD to construct a glucose biosensor. The
      Aushell@GOD nanospheres were investigated with TEM and UV-vis. The ECL behaviors
      of the biosensor were also investigated. Results showed that, the obtained
      Aushell@GOD nanospheres exhibited excellent catalytic effect towards the ECL of
      luminol-H2O2 system. The response of the prepared biosensor to glucose was linear
      with the glucose concentration in the range of 1.0 MUM to 4.3mM (R=0.9923) with a
      detection limit of 0.3 MUM (signal to noise=3). This ECL biosensor exhibited
      short response time and excellent stability for glucose. At the same time the
      prepared ECL biosensor showed good reproducibility, sensitivity and selectivity.

PMID- 25059124
TI  - Geographical characterization of Spanish PDO paprika by multivariate analysis of
      multielemental content.
AB  - A multielemental analytical method has been proposed to determine the contents of
      Al, B, Ca, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, Sr and Zn in paprika samples from
      the two Protected Designations of Origin recognized in Spain, such as Murcia and
      La Vera (Extremadura). The samples are mineralized by acid wet digestion using a
      mixture of perchloric and nitric acids and analyzed by means of inductively
      coupled plasma atomic emission spectroscopy. The method performance has been
      checked studying the absence of matrix effect, trueness, precision, linearity,
      limit of detection and limit of quantification. The proposed method has been
      applied to analyze samples of sweet, hot and hot/sweet paprika from the
      considered production areas. Differences between paprika samples from Murcia and
      Extremadura were found and pattern recognition methods, such as linear
      discriminant analysis, linear support vector machines, soft independent modeling
      of class analogy and multilayer perceptrons artificial neural networks, has been
      used to obtain classification models. Sweet and hot/sweet paprika types were
      differentiated by means of linear models and hot paprika was differentiated by
      using artificial neural networks. A model based on artificial neural networks is
      proposed to differentiate the geographical origin of paprika, with independence
      of the type, leading to an overall classification performance of 99%.

PMID- 25059125
TI  - Analysis of trimethoprim, lincomycin, sulfadoxin and tylosin in swine manure
      using laser diode thermal desorption-atmospheric pressure chemical ionization
      tandem mass spectrometry.
AB  - A new extraction method coupled to a high throughput sample analysis technique
      was developed for the determination of four veterinary antibiotics. The analytes
      belong to different groups of antibiotics such as chemotherapeutics,
      sulfonamides, lincosamides and macrolides. Trimethoprim (TMP), sulfadoxin (SFX),
      lincomycin (LCM) and tylosin (TYL) were extracted from lyophilized manure using a
      sonication extraction. McIlvaine buffer and methanol (MeOH) were used as
      extraction buffers, followed by cation-exchange solid phase extraction (SPE) for
      clean-up. Analysis was performed by laser diode thermal desorption-atmospheric
      pressure chemical-ionization (LDTD-APCI) tandem mass spectrometry (MS/MS) with
      selected reaction monitoring (SRM) detection. The LDTD is a high throughput
      sample introduction method that reduces total analysis time to less than 15s per
      sample, compared to minutes when using traditional liquid chromatography (LC).
      Various SPE parameters were optimized after sample extraction: the stationary
      phase, the extraction solvent composition, the quantity of sample extracted and
      sample pH. LDTD parameters were also optimized: solvent deposition, carrier gas,
      laser power and corona discharge. The method limit of detection (MLD) ranged from
      2.5 to 8.3 ug kg(-1) while the method limit of quantification (MLQ) ranged from
      8.3 to 28ugkg(-1). Calibration curves in the manure matrix showed good linearity
      (R(2)>= 0.996) for all analytes and the interday and intraday coefficients of
      variation were below 14%. Recoveries of analytes from manure ranged from 53% to
      69%. The method was successfully applied to real manure samples.

PMID- 25059126
TI  - Nano sponge Mn2O 3 as a new adsorbent for the preconcentration of Pd(II) and
      Rh(III) ions in sea water, wastewater, rock, street sediment and catalytic
      converter samples prior to FAAS determinations.
AB  - In this study, a nano sponge Mn2O3 adsorbent was synthesized and was used for the
      first time. Various parameters affecting the recovery values of Pd(II) and
      Rh(III) were examined. The tolerance limits (>= 90 %) for both Pd(II) and Rh(III)
      ions were found to be 75,000 mg L(-1) Na(I), 75,000 mg L(-1) K(I), 50,000 mg L(
      1) Mg(II) and 50,000 mg L(-1) Ca(II). A 30s contact time was enough for both
      adsorption and elution. A preconcentration factor of 100 was obtained by using
      100mg of the nano sponge Mn2O3. The reusability of the adsorbent was 120 times.
      Adsorption capacities for Pd(II) and Rh(III) were found to be 42 and 6.2 mg g(
      1), respectively. The detection limits were 1.0 ug L(-1) for Pd(II) and 0.37 ug
      L(-1) for Rh(III) and the relative standard deviations (RSD, %) were found to be
      <= 2.5%. The method was validated by analyzing the standard reference material,
      SRM 2556 (Used Auto Catalyst Pellets) and spiked real samples. The optimized
      method was applied for the preconcentration of Pd(II) and Rh(III) ions in water
      (sea water and wastewater), rock, street sediment and catalytic converter
      samples.

PMID- 25059127
TI  - Multicommutated flow analysis system for determination of total protein in
      cerebrospinal fluid.
AB  - A fully mechanized, computer-controlled, multicommutated flow analysis (MCFA)
      system dedicated for total protein determination in cerebrospinal fluid samples
      has been developed. For the protein determination the Exton method has been
      applied. Dedicated turbidimetric and nephelometric flow-through detectors
      operating according to paired-emitter detector diode principle have been
      fabricated by integration of two or three respective light emitting diodes. The
      developed MCFA system is characterized by robust, compact design and low
      consumption of the sample (72 MU L). The limits of detection for turbidimetric
      and nephelometric detection mode are 65 mg L(-1) and 9 mg L(-1), respectively.
      For turbidimetric measurements the range of linear response offered by the MCFA
      system is 72-900 mg L(-1), whereas in the case of nephelometric detection 18-500
      mg L(-1) linear range is obtained. The throughput of the MCFA system is over 30
      injection per hour. The analytical system was optimized with bovine serum albumin
      standards and successfully validated with real samples of human cerebrospinal
      fluid.

PMID- 25059128
TI  - Detection of heavy-metal ions using liquid crystal droplet patterns modulated by
      interaction between negatively charged carboxylate and heavy-metal cations.
AB  - Herein, we demonstrated a simple, sensitive, and rapid label-free detection
      method for heavy-metal (HM) ions using liquid crystal (LC) droplet patterns on a
      solid surface. Stearic-acid-doped LC droplet patterns were spontaneously
      generated on an n-octyltrichlorosilane (OTS)-treated glass substrate by
      evaporating a solution of the nematic LC, 4-cyano-4'-pentylbiphenyl (5CB),
      dissolved in heptane. The optical appearance of the droplet patterns was a dark
      crossed texture when in contact with air, which represents the homeotropic
      orientation of the LC. This was caused by the steric interaction between the LC
      molecules and the alkyl chains of the OTS-treated surface. The dark crossed
      appearance of the acid-doped LC patterns was maintained after the addition of
      phosphate buffered saline (PBS) solution (pH 8.1 at 25 degrees C). The
      deprotonated stearic-acid molecules self-assembled through the LC/aqueous
      interface, thereby supporting the homeotropic anchoring of 5CB. However, the
      optical image of the acid-doped LC droplet patterns incubated with PBS containing
      HM ions appeared bright, indicating a planar orientation of 5CB at the aqueous/LC
      droplet interface. This dark to bright transition of the LC patterns was caused
      by HM ions attached to the deprotonated carboxylate moiety, followed by the
      sequential interruption of the self-assembly of the stearic acid at the
      LC/aqueous interface. The results showed that the acid-doped LC pattern system
      not only enabled the highly sensitive detection of HM ions at a sub-nanomolar
      concentration but it also facilitated rapid detection (<10 min) with simple
      procedures.

PMID- 25059129
TI  - A novel liquid chromatography-tandem mass spectrometry method for determination
      of menadione in human plasma after derivatization with 3-mercaptopropionic acid.
AB  - Menadione (VK3), an essential fat-soluble naphthoquinone, takes very important
      physiological and pathological roles, but its detection and quantification is
      challenging. Herein, a new method was developed for quantification of VK3 in
      human plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after
      derivatization with 3-mercaptopropionic acid via Michael addition reaction. The
      derivative had been identified by the mass spectra and the derivatization
      conditions were optimized by considering different parameters. The method was
      demonstrated with high sensitivity and a low limit of quantification of 0.03 ng
      mL(-1) for VK3, which is about 33-fold better than that for the direct analysis
      of the underivatized compound. The method also had good precision and
      reproducibility. It was applied in the determination of basal VK3 in human plasma
      and a clinical pharmacokinetic study of menadiol sodium diphosphate. Furthermore,
      the method for the quantification of VK3 using LC-MS/MS was reported in this
      paper for the first time, and it will provide an important strategy for the
      further research on VK3 and menadione analogs.

PMID- 25059130
TI  - Determination of hexabromocyclododecane by flowing atmospheric pressure afterglow
      mass spectrometry.
AB  - The first application of a flowing atmospheric-pressure afterglow ion source for
      mass spectrometry (FAPA-MS) for the chemical characterization and determination
      of hexabromocyclododecane (HBCD) is presented. The samples of technical HBCD and
      expanded polystyrene foam (EPS) containing HBCD as a flame retardant were
      prepared by dissolving the appropriate solids in dichloromethane. The ionization
      of HBCD was achieved with a prototype FAPA source. The ions were detected in the
      negative-ion mode. The ions corresponding to a deprotonated HBCD species (m/z
      640.7) as well as chlorine (m/z 676.8), nitrite (m/z 687.8) and nitric (m/z
      703.8) adducts were observed in the spectra. The observed isotope pattern is
      characteristic for a compound containing six bromine atoms. This technique is an
      effective approach to detect HBCD, which is efficiently ionized in a liquid
      phase, resulting in high detection efficiency and sensitivity. 

PMID- 25059131
TI  - Determination of nucleating agents in plastic materials by GC/MS after microwave
      assisted extraction with in situ microwave-assisted derivatization.
AB  - This work demonstrates the analysis of sorbitol-based nucleating and clarifying
      agents (NCAs) used as additives for polyolefin-based materials by gas
      chromatography/mass spectrometry (GC/MS), employing a highly reliable and
      efficient sample preparation methodology applying microwave irradiation. A
      derivatization by silylation of the analytes was done to improve the GC
      suitability of the analytes. After successful optimization of the conditions for
      a microwave-assisted derivatization (MAD), the microwave-assisted extraction
      (MAE) of the analytes from polymer samples was investigated. Tetrahydrofuran
      (THF) turned out to be the best extraction solvent, as poorly soluble analytes
      show the highest solubility in this solvent and THF supports the silylation after
      extraction. This two-step approach and subsequent chromatographic determination
      resulted in reproducibilities from approximately 2% up to 6% and recoveries from
      95.8% up to 104.2% in real samples. In order to reduce the number of sample
      preparation steps a one-step approach was investigated and optimized, in which
      MAE and MAD were carried out simultaneously. The developed procedure resulted in
      remarkably better repeatabilities ranging from 0.05% up to 4% and
      reproducibilities of up to 10%. The recoveries matched those obtained with the
      two-step process. Linearities could be achieved in both approaches with R(2)
      better than 0.99 for all selected analytes over two orders of magnitude. All data
      indicate the suitability of both presented methods for the reliable determination
      of sorbitol-based NCAs in polyolefin materials. 

PMID- 25059132
TI  - A fluorescence ratiometric chemosensor for Fe3+ based on TBET and its application
      in living cells.
AB  - Based on a through bond energy transfer (TBET) between rhodamine and
      naphthalimide fluorophores, a fluorescent ratiometric chemosensor L was designed
      and prepared for highly selective detection of Fe(3+) in aqueous solution and in
      living EC109 cells. These significant changes in the fluorescence color could be
      used for naked-eye detection. The reversibility established the potential of the
      probe as chemosensor for Fe(3+) detection. 

PMID- 25059133
TI  - Comparison of sample preparation methods for reliable plutonium and neptunium
      urinalysis using automatic extraction chromatography.
AB  - This paper describes improvement and comparison of analytical methods for
      simultaneous determination of trace-level plutonium and neptunium in urine
      samples by inductively coupled plasma mass spectrometry (ICP-MS). Four sample pre
      concentration techniques, including calcium phosphate, iron hydroxide and
      manganese dioxide co-precipitation and evaporation were compared and the
      applicability of different techniques was discussed in order to evaluate and
      establish the optimal method for in vivo radioassay program. The analytical
      results indicate that the various sample pre-concentration approaches afford
      dissimilar method performances and care should be taken for specific experimental
      parameters for improving chemical yields. The best analytical performances in
      terms of turnaround time (6h) and chemical yields for plutonium (88.7 +/- 11.6%)
      and neptunium (94.2 +/- 2.0%) were achieved by manganese dioxide co
      precipitation. The need of drying ashing (>= 7h) for calcium phosphate co
      precipitation and long-term aging (5d) for iron hydroxide co-precipitation,
      respectively, rendered time-consuming analytical protocols. Despite the fact that
      evaporation is also somewhat time-consuming (1.5d), it endows urinalysis methods
      with better reliability and repeatability compared with co-precipitation
      techniques. In view of the applicability of different pre-concentration
      techniques proposed previously in the literature, the main challenge behind
      relevant method development is pointed to be the release of plutonium and
      neptunium associated with organic compounds in real urine assays. In this work,
      different protocols for decomposing organic matter in urine were investigated, of
      which potassium persulfate (K2S2O8) treatment provided the highest chemical yield
      of neptunium in the iron hydroxide co-precipitation step, yet, the occurrence of
      sulfur compounds in the processed sample deteriorated the analytical performance
      of the ensuing extraction chromatographic separation with chemical yields of <=
      50%.

PMID- 25059134
TI  - Stability of toxic arsenic species and arsenosugars found in the dry alga Hijiki
      and its water extracts.
AB  - The achievement of reliable results in speciation analysis requires not only
      sensitive techniques but also sureness of species stability. Therefore, it is
      necessary to carry out stability studies because it is important to know with
      absolute certainty that there is not any species transformation during sample
      treatment and/or storage. Although several procedures have been recommended for
      the preservation of species integrity, there is no general agreement, as arsenic
      species stability depends on the sample matrix, the concentration level and the
      sample treatment procedure, so it is necessary to assess the arsenic species
      stability for each case. Thus, the present paper reports the stability tests of
      arsenic species carried out on the commercially available edible alga Hijiki
      (Hizikia fusiformis), from Japan, in both the dry sample and its water extracts,
      which were stored in amber glass and polystyrene containers at -18 and +4 degrees
      C in the dark. Extractions were carried out with deionized water by microwave
      assisted extraction, at a temperature of 90 degrees C and three extraction steps
      of 5 min each, whereas arsenic speciation analysis was performed by anion
      exchange high performance liquid chromatography-photo-oxidation-hydride
      generation-atomic fluorescence spectrometry. The results obtained for the dry
      alga showed that the arsenic species present in it (arsenate (As(V)),
      dimethylarsinic acid (DMA) and the arsenosugars glycerol (Gly-sug), phosphate
      (PO4-sug), sulfonate (SO3-sug) and sulfate (SO4-sug)) were stable for at least 12
      months when the sample was stored in polystyrene containers at +20 degrees C in
      the dark. Regarding water extracts, the best storage conditions consisted of the
      use of polystyrene containers and a temperature of +4 degrees C, for a maximum
      storage time of seven days. Therefore, the immediate analysis of Hijiki water
      extracts would not be necessary, and they could be stored for one week before
      analysis, ensuring arsenic species stability. This information about species
      integrity in extracts is especially useful when the sample treatment for arsenic
      species extraction is time-consuming.

PMID- 25059135
TI  - Application of CE-MS to examination of black inkjet printing inks for forensic
      purposes.
AB  - The potential of capillary electrophoresis coupled to mass spectrometry with
      electrospray ion source and time of flight analyser (CE-ESI-TOF-MS) in the
      analysis of inkjet inks was investigated. The developed and validated method
      allowed reliable and repeatable analysis of black inkjet inks extracted from
      printouts. Over a dozen inkjet printouts printed on various printer models from
      different manufacturers were analysed under selected conditions to determine the
      variation of chemical composition of inks between different brands and types. It
      was ascertained that the developed method is capable of revealing qualitative
      differences between ink samples. For most of the investigated inks, the studies
      showed the presence of a characteristic mass spectrum originating from the
      surfactant or polymer. The mass distribution of the additive is distinctive for
      some inkjet ink producers, and allows for group identification of inks. The
      results showed the strength of the CE-ESI-TOF-MS method as an effective technique
      for forensic purposes, requiring a small amount of inkjet ink samples and giving
      analytical information that is useful in the identification of compounds. 

PMID- 25059136
TI  - Liquid-liquid extraction of divalent transition metal ions with a novel bis-beta
      ketoester extraction reagent.
AB  - Solvent extraction is a very effective method for the separation of metal ions.
      N,N'-bis(2-hydroxy-phenylmethyl)-N,N'-bis(2-pyridylmetyl)-1,2-ethanediamine
      derivatives have been researched for solvent extraction of metal ions. In this
      study. We synthesized a bis-beta-ketoester ligand and evaluated its selectivity
      in extracting divalent transition metal ions. The ligand, hexane-1,6-diyl bis
      (4,4,4-trifluoro-3-oxobutanoate) (H2hdfob or H2L) was synthesized in one step by
      transesterification of ethyl 4,4,4-trifluoroacetoacetate with 1,6-hexanediol. The
      multidentate ligand H2hdfob successfully extracted divalent transition metal ions
      into its organic phase. The relationship between logD, which is a distribution
      ratio (D), and pH or log[H2L]o exhibited linear relationships with slopes of
      approximately +2 and +1, respectively. Based on these results, we proposed a
      mechanism of extraction with H2hdfob. Extraction with tetradentate H2hdfob
      provides a new method for enhancing selectivity of divalent metal ions, in
      comparison to other bidentate ligands.

PMID- 25059137
TI  - Laboratory and field validation of a Cry1Ab protein quantitation method for
      water.
AB  - The widespread planting of crops expressing insecticidal proteins derived from
      the soil bacterium Bacillus thuringiensis (Bt) has given rise to concerns
      regarding potential exposure to non-target species. These proteins are released
      from the plant throughout the growing season into soil and surface runoff and may
      enter adjacent waterways as runoff, erosion, aerial deposition of particulates,
      or plant debris. It is crucial to be able to accurately quantify Bt protein
      concentrations in the environment to aid in risk analyses and decision making.
      Enzyme-linked immunosorbent assay (ELISA) is commonly used for quantitation of Bt
      proteins in the environment; however, there are no published methods detailing
      and validating the extraction and quantitation of Bt proteins in water. The
      objective of the current study was to optimize the extraction of a Bt protein,
      Cry1Ab, from three water matrices and validate the ELISA method for specificity,
      precision, accuracy, stability, and sensitivity. Recovery of the Cry1Ab protein
      was matrix-dependent and ranged from 40 to 88% in the validated matrices, with an
      overall method detection limit of 2.1 ng/L. Precision among two plates and within
      a single plate was confirmed with a coefficient of variation less than 20%. The
      ELISA method was verified in field and laboratory samples, demonstrating the
      utility of the validated method. The implementation of a validated extraction and
      quantitation protocol adds consistency and reliability to field-collected data
      regarding transgenic products.

PMID- 25059138
TI  - A novel paper rag as 'D-SERS' substrate for detection of pesticide residues at
      various peels.
AB  - Many important considerations in the design of practical Surface enhanced Raman
      spectroscopy (SERS) substrates are necessary, such as the low cost, simple
      preparation, mass production and high efficiency of sample collection, which the
      conventional rigid substrates are lack of. In this work, practical SERS
      substrates based on deposition of silver nanoparticles (Ag NPs) on commercially
      available low-cost filter paper were prepared by simple silver mirror reaction in
      a large scale, and utilized for rapid, portable and accurate identification and
      detection of pesticide residues at various peels. Compared with conventional
      substrates, this novel SERS substrate dramatically enhanced the sample collection
      efficiency by simply swabbing paper-based device across different surfaces
      without destroying the sample, meanwhile avoiding the substrate signal of real
      world samples. Considering their low cost, portability, simplicity and high
      sample collection efficiency, Ag NP-decorated filter paper, as practical SERS
      substrate, are used in solving critical problems for detection of pesticide
      residues at various peels. SERS experiments were carried out on Ag NP-decorated
      filter paper combined with 'dynamic SERS' (D-SERS) due to its high detection
      sensitivity. The excellent detection performance of the Ag NP-based filter paper
      was demonstrated by detection thiram and paraoxon residues at various peels.
      Besides, the stability and reproducibility of the practical substrates were also
      involved. 

PMID- 25059139
TI  - Development of a GC-MS/MS strategy to determine 15 mycotoxins and metabolites in
      human urine.
AB  - The widespread mycotoxins contamination of food commodities has made the
      monitoring of their levels essential. To overcome the disadvantages of the
      indirect approach by food analysis, detection of mycotoxin as biomarkers in urine
      provides a useful and specific data for exposure assessment to these food
      contaminants. In this work, a sensitive, rapid and accurate method based on gas
      chromatography-tandem mass spectrometry procedure to determine 15 mycotoxins and
      metabolites in human urine was optimized and validated taking into consideration
      the guidelines specified in Commission Decision 2002/657/EC and 401/2006/EC. A
      salting-out assisted acetonitrile-based extraction was used for sample
      preparation. The extraction recoveries were in a range of 72-109%, with intra-day
      relative standard deviation and inter-day relative standard deviation lower than
      10% and 13%, respectively for all mycotoxins at 50, 100 and 200 ug/L spiking
      levels. The limits of quantitation ranged from 0.25 to 8 ug/L. Matrix effect was
      evaluated and matrix-matched calibration was used for quantitation. The proposed
      procedure was applied to 10 urine samples collected from children. Mycotoxins
      were quantified in 30% of samples.

PMID- 25059140
TI  - Lead detection using micro/nanocrystalline boron-doped diamond by square-wave
      anodic stripping voltammetry.
AB  - Monitoring heavy metal ion levels in water is essential for human health and
      safety. Electroanalytical techniques have presented important features to detect
      toxic trace heavy metals in the environment due to their high sensitivity
      associated with their easy operational procedures. Square-wave voltammetry is a
      powerful electrochemical technique that may be applied to both electrokinetic and
      analytical measurements, and the analysis of the characteristic parameters of
      this technique also enables the mechanism and kinetic evaluation of the
      electrochemical process under study. In this work, we present a complete
      optimized study on the heavy metal detection using diamond electrodes. It was
      analyzed the influence of the morphology characteristics as well as the doping
      level on micro/nanocrystalline boron-doped diamond films by means of square-wave
      anodic stripping voltammetry (SWASV) technique. The SWASV parameters were
      optimized for all films, considering that their kinetic response is dependent on
      the morphology and/or doping level. The films presented reversible results for
      the Lead [Pb (II)] system studied. The Pb (II) analysis was performed in ammonium
      acetate buffer at pH 4.5, varying the lead concentration in the range from 1 to
      10 MUg L(-1). The analytical responses were obtained for the four electrodes.
      However, the best low limit detection and reproducibility was found for boron
      doped nanocrystalline diamond electrodes (BDND) doped with 2000 mg L(-1) in B/C
      ratio.

PMID- 25059141
TI  - Analytical method for biomonitoring of perfluoroalkyl acids in human urine.
AB  - Perfluoroalkyl acids are an important class of synthetic compounds widely used in
      commercial and residential settings, which may have potential adverse health
      effects. The objective of this study was to monitor 6 perfluorocarboxylic acids
      and perfluorooctane sulphonate in human urine to obtain a way to asses exposure.
      The target analytes were extracted from urine by using a semi automated solid
      phase extraction module and derivatised with isobutyl chloroformate by catalysis
      with 3% N,N-dicyclohexylcarbodiimide in pyridine. Determination and quantisation
      were achieved by gas chromatography with a mass spectrometer detector operating
      in the selected-ion monitoring mode. The developed approach is fast and provided
      low limits of detection (0.2-1.0 ng L(-1)) with good precision (relative standard
      deviation lower than 7.5%, within-day and between day). Recoveries from urine
      samples, which were spiked with the studied compounds at levels of 10 and 50 ng
      L(-1) ranged from 93% to 96%. Perfluorohexanoic (<= 70 ng L(-1)) and
      perfluoroheptanoic acids (<2 ng L(-1)) were found in the urine samples from
      exposed researchers taken after handling these compounds. From the calculation of
      the excretion kinetics it was found that the dosage absorbed was eliminated
      within 15 h after exposure.

PMID- 25059142
TI  - Speciation of As(III)/As(V) in water samples by a magnetic solid phase extraction
      based on Fe3O4/Mg-Al layered double hydroxide nano-hybrid followed by
      chemiluminescence detection.
AB  - A novel magnetic solid phase extraction method was developed for the speciation
      of As(III)/As(V) in aqueous solutions utilizing Fe3O4-doped Mg-Al layered double
      hydroxide (LDH) as a nano-sorbent. The method is based on the separation and pre
      concentration of As(V) by Fe3O4/Mg-Al LDH nano-hybrid prior to determination by a
      chemiluminescence (CL) technique. The CL route involves the oxidation of luminol
      by vanadomolybdoarsenate heteropoly acid in a basic media. Since the existing
      cations cannot be adsorbed by positively charged layers of the LDH and other
      potentially interferent anions had no considerable effect on the CL reaction, it
      provides a very selective and sensitive determination approach for As(V). The
      determination of total arsenic and hence indirectly As(III) involve the pre
      oxidation of As(III) to As(V) by a mixture of hydrogen peroxide and potassium
      hydroxide. Several factors affecting the extraction and determination of the
      analyte were investigated and optimized. Under optimum conditions, the
      calibration graph was linear in the range of 5.0-5000 ng L(-1). The limit of
      detection and enrichment factor was 2.0 ng L(-1) and 80, respectively. The method
      was validated by the analysis of a standard reference material (NIST SRM 1643e),
      and successfully applied to the speciation of arsenic in several water samples
      with recoveries in the range of 93.3-106.7% for the spiked samples.

PMID- 25059143
TI  - Suspected-target pesticide screening using gas chromatography-quadrupole time-of
      flight mass spectrometry with high resolution deconvolution and retention
      index/mass spectrum library.
AB  - A strategy for suspected-target screening of pesticide residues in complicated
      matrices was exploited using gas chromatography in combination with hybrid
      quadrupole time-of-flight mass spectrometry (GC-QTOF MS). The screening workflow
      followed three key steps of, initial detection, preliminary identification, and
      final confirmation. The initial detection of components in a matrix was done by a
      high resolution mass spectrum deconvolution; the preliminary identification of
      suspected pesticides was based on a special retention index/mass spectrum (RI/MS)
      library that contained both the first-stage mass spectra (MS(1) spectra) and
      retention indices; and the final confirmation was accomplished by accurate mass
      measurements of representative ions with their response ratios from the MS(1)
      spectra or representative product ions from the second-stage mass spectra (MS(2)
      spectra). To evaluate the applicability of the workflow in real samples, three
      matrices of apple, spinach, and scallion, each spiked with 165 test pesticides in
      a set of concentrations, were selected as the models. The results showed that the
      use of high-resolution TOF enabled effective extractions of spectra from noisy
      chromatograms, which was based on a narrow mass window (5 mDa) and suspected
      target compounds identified by the similarity match of deconvoluted full mass
      spectra and filtering of linear RIs. On average, over 74% of pesticides at 50
      ng/mL could be identified using deconvolution and the RI/MS library. Over 80% of
      pesticides at 5 ng/mL or lower concentrations could be confirmed in each matrix
      using at least two representative ions with their response ratios from the MS(1)
      spectra. In addition, the application of product ion spectra was capable of
      confirming suspected pesticides with specificity for some pesticides in
      complicated matrices. In conclusion, GC-QTOF MS combined with the RI/MS library
      seems to be one of the most efficient tools for the analysis of suspected-target
      pesticide residues in complicated matrices.

PMID- 25059144
TI  - Combined cloud point-solid phase extraction by dispersion of TiO2 nanoparticles
      in micellar media followed by semi-microvolume UV-vis spectrophotometric
      detection of zinc.
AB  - A new approach is presented in this paper by using dispersed TiO2 nanoparticles
      (TiO2-NPs) in a combined cloud point and solid phase extraction for the efficient
      preconcentration and determination of Zn(2+) in various samples. In this method
      Zn(2+) ions are adsorbed on TiO2-NPs and transferred into surfactant rich phase.
      Subsequently the Zn(2+) ions are desorbed from TiO2-NPs by a dithizone solution
      via forming a color complex which could be detected colorimetrically. The
      influence of chemical variables such as pH of the sample solution, electrolyte,
      amount of TiO2-NPs, type and volume of the eluent on the extraction system was
      studied. The calibration graph was linear in the range of 0.5-90.0 ug L(-1) of
      Zn(2+) (r=0.9996). An enrichment factor of 80 was achieved and the limit of
      detection for Zn(2+) was 0.33 ug L(-1). The relative standard deviation (RSD) for
      eight replicate measurements of 10 ug L(-1) and 60 ug L(-1) of Zn(2+) was 1.8%
      and 1.5% respectively. The proposed method was successfully applied to the
      quantitative determination of Zn(2+) in tap water, powder milk and Zinc sulfate
      tablet with satisfactory results.

PMID- 25059145
TI  - Magnetic dummy molecularly imprinted polymers based on multi-walled carbon
      nanotubes for rapid selective solid-phase extraction of 4-nonylphenol in aqueous
      samples.
AB  - In this paper, a highly selective sample clean-up procedure combining magnetic
      dummy molecular imprinting with solid-phase extraction was developed for rapid
      separation and determination of 4-nonylphenol (NP) in the environmental water
      samples. The magnetic dummy molecularly imprinted polymers (mag-DMIPs) based on
      multi-walled carbon nanotubes were successfully synthesized with a surface
      molecular imprinting technique using 4-tert-octylphenol as the dummy template and
      tetraethylorthosilicate as the cross-linker. The maximum adsorption capacity of
      the mag-DMIPs for NP was 52.4 mg g(-1) and it took about 20 min to achieve the
      adsorption equilibrium. The mag-DMIPs exhibited the specific selective adsorption
      toward NP. Coupled with high performance liquid chromatography analysis, the mag
      DMIPs were used to extract solid-phase and detect NP in real water samples
      successfully with the recoveries of 88.6-98.1%.

PMID- 25059146
TI  - Cardiovascular disease detection using bio-sensing techniques.
AB  - Universally, cardiovascular disease (CVD) is recognised as the prime cause of
      death with estimates exceeding 20 million by 2015 due to heart disease and
      stroke. Facts regarding the disease, its classification and diagnosis are still
      lacking. Hence, understanding the issues involved in its initiation, its symptoms
      and early detection will reduce the high risk of sudden death associated with it.
      Biosensors developed to be used as rapid screening tools to detect disease
      biomarkers at the earliest stage and able to classify the condition are
      revolutionising CVD diagnosis and prognosis. Advances in interdisciplinary
      research areas have made biosensors faster, highly accurate, portable and
      environmentally friendly diagnostic devices. The recent advances in microfluidics
      and the advent of nanotechnology have resulted in the development of improved
      diagnostics through reduction of analysis time and integration of several
      clinical assays into a single, portable device as lab-on-a-chip (LOC). The
      development of such affinity based systems is a major drive of the rapidly
      growing nanotechnology industry which involves a multidisciplinary research
      effort encompassing nanofluidics, microelectronics and analytical chemistry. This
      review summarised the classification of CVD, the biomarkers used for its
      diagnosis, biosensors and their application including the latest developments in
      the field of heart-disease detection. 

PMID- 25059147
TI  - Development of a non-denaturing 2D gel electrophoresis protocol for screening in
      vivo uranium-protein targets in Procambarus clarkii with laser ablation ICP MS
      followed by protein identification by HPLC-Orbitrap MS.
AB  - Limited knowledge about in vivo non-covalent uranium (U)-protein complexes is
      largely due to the lack of appropriate analytical methodology. Here, a method for
      screening and identifying the molecular targets of U was developed. The approach
      was based on non-denaturing 1D and 2D gel electrophoresis (ND-PAGE and ND-2D-PAGE
      (using ND-IEF as first dimension previously described)) in conjunction with laser
      ablation inductively coupled plasma mass spectrometry (LA-ICP MS) for the
      detection of U-containing proteins. The proteins were then identified by ubore
      HPLC-Orbitrap MS/MS. The method was applied to the analysis of cytosol of
      hepatopancreas (HP) of a model U-bioaccumulating organism (Procambarus clarkii).
      The imaging of uranium in 2D gels revealed the presence of 11 U-containing
      protein spots. Six protein candidates (i.e. ferritin, glyceraldehyde-3-phosphate
      dehydrogenase, triosephosphate isomerase, cytosolic manganese superoxide
      dismutase (Mn-SOD), glutathione S transferase D1 and H3 histone family protein)
      were then identified by matching with the data base of crustacea Decapoda species
      (e.g. crayfish). Among them, ferritin was the most important one. This strategy
      is expected to provide an insight into U toxicology and metabolism. 

PMID- 25059148
TI  - Gold nanorods for surface Plasmon resonance detection of mercury (II) in flow
      injection analysis.
AB  - This article investigates the flow injection analysis of mercury (II) ions in tap
      water samples via surface Plasmon resonance detection. Quantitative analysis of
      mercury (II) is based on the chemical interaction of metallic mercury with gold
      nanorods immobilized on a glass substrate. A new flow cell design is presented
      with the ability to accommodate the detecting substrate in the sample compartment
      of commercial spectrometers. Two alternatives are here considered for mercury
      (II) detection, namely stop-flow and continuous flow injection analysis modes.
      The best limit of detection (2.4 ng mL(-1)) was obtained with the continuous flow
      injection analysis approach. The accurate determination of mercury (II) ions in
      samples of unknown composition is demonstrated with a fortified tap water sample.

PMID- 25059149
TI  - A sensitive electrochemical sensor for rapid determination of methadone in
      biological fluids using carbon paste electrode modified with gold nanofilm.
AB  - A novel and effective electrochemical sensor for the determination of methadone
      (MET) at pH 9.0 using gold nanoparticles, electrodeposited on a multi-walled
      carbon nanotube modified carbon paste electrode (GNPs/MWCPE), is introduced. The
      voltammetric behavior of MET at this modified electrode was studied using cyclic
      and square wave voltammetric techniques and the results were compared with those
      obtained at the multi-walled carbon nanotube modified carbon paste electrode
      (MWCPE). The oxidation of MET was irreversible and exhibited an adsorption
      controlled process at the GNPs/MWCPE and a diffusion controlled process at the
      MWCPE. The effect of various experimental parameters including pH, scan rate, and
      accumulation potential and time on the voltammetric response of MET was
      investigated. At the optimum conditions, the concentration of MET was determined
      using square wave voltammetry (SWV) in a linear range of 0.1-500.0 umol L(-1)
      with a correlation coefficient of 0.9901 at the GNPs/MWCPE, and 0.5-300.0 umol L(
      1) with a correlation coefficient of 0.993 at the MWCPE and the detection limits
      were found to be 0.005 and 0.3 umol L(-1), respectively. The proposed electrode
      was successfully applied to the determination of MET in a pharmaceutical dosage
      form, urine and saliva samples. The effects of common interferences, namely some
      of different cations and anions, on the current response of MET were
      investigated. This revealed that the GNPs/MWCPE shows excellent analytical
      performance for the determination of MET in terms of a very low detection limit,
      high sensitivity, very good repeatability and reproducibility.

PMID- 25059150
TI  - A bimodal optoelectronic flow-through detector for phosphate determination.
AB  - A miniature flow-through detector useful for bimodal, photometric and
      fluorimetric, determination of phosphates has been developed. This optoelectronic
      device made of four light emitting diodes (LEDs) integrated in the form of 85 uL
      optical cell is easily applied in flow analysis manifolds. These LEDs play the
      roles of light source for photometric measurements, fluorescence inductors and
      detector of absorbance and fluorescence. For photometric mode of determinations a
      phosphomolybdenum blue method has been applied. The fluorimetric method of
      phosphate determination is based on quenching of rhodamine fluorescence by the
      heteropolyacid. The developed detector used in a simple three-channel flow
      injection analysis (FIA) system allows photometric or fluorimetric determination
      of phosphate in the wide range of concentration. The detection limits found for
      photometric and fluorimetric modes of FIA measurements are 5.5 mg L(-1) and 10.4
      ug L(-1), respectively. The potential utility of the flow-through detector for
      the needs of food and clinical analysis has been demonstrated.

PMID- 25059151
TI  - Glutathione and L-cysteine modified silver nanoplates-based colorimetric assay
      for a simple, fast, sensitive and selective determination of nickel.
AB  - A novel colorimetric assay based on silver nanoplates (AgNPls) for detecting
      nickel ions (Ni(2+)) has been developed. Glutathione (GSH) and l-cysteine (Cys)
      were used to modify the AgNPls surface, exhibiting extremely high selectivity
      towards Ni(2+) over other metal ions under specific conditions. Upon addition of
      Ni(2+) to the modified AgNPls solution, a distinctive color change can be clearly
      observed by naked eyes as a result of the aggregation of AgNPls induced by the
      binding between Ni(2+) and the modified ligands. To verify a complete self
      assembly of the GSH and Cys onto AgNPls surface, the modified AgNPls were
      characterized using Fourier transform infrared spectroscopy (FTIR), ultraviolet
      visible spectroscopy (UV-vis) and transmission electron microscopy (TEM),
      respectively. Moreover, various parameters affecting the Ni(2+) quantification
      including the modifier ratio, pH, reaction time, and interferences were
      investigated. With UV-vis spectrophotometric measurement under optimal
      conditions, a quantitative linearity was established in the range of 10-150 ppb
      (R(2)=0.9971) with the detection limit of 7.02 ppb or 120 nM (S/N=3). In
      addition, the developed sensor was applied to the determination of Ni(2+) in
      waste samples from a jewelry factory and a car manufacturer with satisfactory
      results. Overall, this alternative approach presents a simple, rapid, sensitive
      and selective detection of Ni(2+).

PMID- 25059152
TI  - Development of a targeted method for twenty-three metabolites related to
      polyphenol gut microbial metabolism in biological samples, using SPE and UHPLC
      ESI-MS/MS.
AB  - An increasing number of studies have concerned the profiling of polyphenol
      microbial metabolites, especially in urine or plasma, but only a few have
      regarded their accurate quantification. This study reports on a new ultra
      performance liquid chromatography tandem mass spectrometry method with
      electrospray ionisation (UHPLC-ESI-MS/MS) using a simple clean-up step with solid
      phase extraction (SPE) and validation on different biological matrices. The
      method was tested with spiked samples of liver, heart, kidneys, brain, blood and
      urine. The purification procedure, after the evaluation of three different
      cartridges, makes it possible to obtain cleaner samples and better quantification
      of putative trace metabolites, especially related to dietary studies, with
      concentrations below ng/g in tissue and for urine and blood, starting from ng/ml.
      Limits of detection and linear range were also assessed using mixed polyphenol
      metabolite standards. Short chromatographic separation was carried out for 23
      target compounds related to the polyphenol microbial metabolism, coupled with a
      triple quadrupole mass spectrometer for their accurate quantification. By
      analysing different spiked biological samples we were able to test metabolite
      detection in the matrix and validate the overall recovery of the method, from
      purification to quantification. The method developed can be successfully applied
      and is suitable for high-throughput targeted metabolomics analysis related to
      nutritional intervention, or the study of the metabolic mechanism in response to
      a polyphenol-rich diet. 

PMID- 25059153
TI  - Novel unbreakable solid-phase microextraction fibers on stainless steel wire and
      application for the determination of oxadiargyl in environmental and agricultural
      samples in combination with gas chromatography-mass spectrometry.
AB  - Sol-gel based solid-phase microextraction fibers supported by a stainless steel
      wire were fabricated and employed for GC-MS determination of oxadiargyl in real
      samples. The fibers were based on four compounds with different polarity: polar
      and non-polar (end-capped) poly(dimethylsiloxane) (PDMS), polyethylene glycol
      (PEG), and poly(ethylene-propyleneglycol)-monobutyl ether (UCON). For this
      purpose, the surface of the stainless steel was initially modified by (3
      mercaptopropyl) trimethoxysilane. The results of the modification procedure were
      evaluated by cyclic voltammetry and energy dispersive X-ray (EDX) spectroscopy.
      After the modification, four different sol-gel based SPME fibers with different
      values of polarity, polar and non-polar PDMS, PEG, and UCON have been prepared
      and investigated. They are supposed to be employed to determinate oxadiargyl in
      agricultural and environmental samples prior to gas chromatography-mass
      spectrometry analysis. Most important parameters that affect the extraction
      efficiency were also optimized. Under optimized conditions, the proposed method
      was found to be linear for the concentrations ranging from 100 ng L(-1) to 2 mg
      L(-1) with R(2)=0.997. Limit of detection (LOD) of 40 ng L(-1) and relative
      standard deviation of less than 10% were obtained. Relative recovery in
      environmental and agricultural samples was in the range of 73-96%.

PMID- 25059154
TI  - Terminal protection of small molecule-linked ssDNA for label-free and sensitive
      fluorescent detection of folate receptor.
AB  - In this work, based on terminal protection of folate-linked ssDNA (FA-ssDNA) and
      the SYBR Gold fluorescent dye, we describe the development of a label-free
      fluorescent strategy for the detection of folate receptors (FRs). The binding
      between the target FR and the FA moiety of the FA-ssDNA protects the FR bound FA
      ssDNA from digesting by Exo I. The binding of SYBR Gold to the terminal
      protected, un-digested FA-ssDNA leads to enhanced fluorescent emission for the
      monitoring of FR with a detection limit of 30 pM. Besides, the developed method
      also shows high selectivity toward FR against other control proteins. Moreover,
      our approach avoids the labeling of the probes with fluorescent tags and achieves
      label-free detection of FR. With these advantages, the proposed method thus holds
      promising potential for the development of simple and convenient strategies for
      the detection of other proteins by using different small molecule
      receptor/protein ligand pairs.

PMID- 25059155
TI  - Intensification of the electrochemiluminescence of luminol on hollow TiO2
      nanoshell-modified indium tin oxide electrodes.
AB  - Hollow titania nanoshells (HTNSs), which were synthesized by a SiO2 sacrificial
      template method, were used to intensify the electrochemiluminescence (ECL) of
      luminol. The size, shell thickness and crystal phase, factors that are important
      in determining the efficiency, can be controlled by adjusting the template size,
      precursor concentration and calcination temperature, respectively. The structure
      of the HTNSs was characterized by transmission electron microscopy, scanning
      electron microscopy and X-ray diffraction spectroscopy. After structural
      optimization, the surface of indium tin oxide (ITO)-coated glass was modified
      with the HTNSs to act as a working electrode for a flow-injection analytical
      system. The heterostructure demonstrated an ECL emission intensity 150 times
      higher than that of the bare ITO. The research also revealed that the ECL of
      luminol on this modified electrode showed a very sensitive response to hydrogen
      peroxide with a detection limit of 4.6*10(-10)M. In addition to discussing the
      intensifying mechanism of luminol ECL by HTNSs, we demonstrate that can be
      successfully applied to evaluate the gross antioxidant activity of garlic.

PMID- 25059156
TI  - Validation of a continuous flow method for the determination of soluble iron in
      atmospheric dust and volcanic ash.
AB  - Iron is an essential micronutrient for phytoplankton growth and is supplied to
      the remote areas of the ocean mainly through atmospheric dust/ash. The amount of
      soluble Fe in dust/ash is a major source of uncertainty in modeling-Fe
      dissolution and deposition to the surface ocean. Currently in the literature,
      there exist almost as many different methods to estimate fractional solubility as
      researchers in the field, making it difficult to compare results between research
      groups. Also, an important constraint to evaluate Fe solubility in atmospheric
      dust is the limited mass of sample which is usually only available in micrograms
      to milligrams amounts. A continuous flow (CF) method that can be run with low
      mass of sediments (<10mg) was tested against a standard method which require
      about 1g of sediments (BCR of the European Union). For validation of the CF
      experiment, we run both methods using South American surface sediment and
      deposited volcanic ash. Both materials tested are easy eroded by wind and are
      representative of atmospheric dust/ash exported from this region. The uncertainty
      of the CF method was obtained from seven replicates of one surface sediment
      sample, and shows very good reproducibility. The replication was conducted on
      different days in a span of two years and ranged between 8 and 22% (i.e., the
      uncertainty for the standard method was 6-19%). Compared to other standardized
      methods, the CF method allows studies of dissolution kinetic of metals and
      consumes less reagents and time (<3h). The method validated here is suggested to
      be used as a standardized method for Fe solubility studies on dust/ash. 

PMID- 25059157
TI  - Second-order data obtained by beta-cyclodextrin complexes: a novel approach for
      multicomponent analysis with three-way multivariate calibration methods.
AB  - This research reports the first application of beta-cyclodextrin (beta-CD)
      complexes as a new method for generation of three way data, combined with second
      order calibration methods for quantification of a binary mixture of caffeic (CA)
      and vanillic (VA) acids, as model compounds in fruit juices samples. At first,
      the basic experimental parameters affecting the formation of inclusion complexes
      between target analytes and beta-CD were investigated and optimized. Then under
      the optimum conditions, parallel factor analysis (PARAFAC) and bilinear least
      squares/residual bilinearization (BLLS/RBL) were applied for deconvolution of
      trilinear data to get spectral and concentration profiles of CA and VA as a
      function of beta-CD concentrations. Due to severe concentration profile
      overlapping between CA and VA in beta-CD concentration dimension, PARAFAC could
      not be successfully applied to the studied samples. So, BLLS/RBL performed better
      than PARAFAC. The resolution of the model compounds was possible due to
      differences in the spectral absorbance changes of the beta-CD complexes signals
      of the investigated analytes, opening a new approach for second-order data
      generation. The proposed method was validated by comparison with a reference
      method based on high-performance liquid chromatography photodiode array detection
      (HPLC-PDA), and no significant differences were found between the reference
      values and the ones obtained with the proposed method. Such a chemometrics-based
      protocol may be a very promising tool for more analytical applications in real
      samples monitoring, due to its advantages of simplicity, rapidity, accuracy,
      sufficient spectral resolution and concentration prediction even in the presence
      of unknown interferents.

PMID- 25059158
TI  - Sensitive multiplexed DNA detection using silica nanoparticles as the target
      capturing platform.
AB  - We present a simple and sensitive method for multiplexed DNA detection by
      simultaneously capturing two different DNA sequences with a same silica
      nanoparticle (NP) through a sandwich mode. This biobarcode assay method was
      demonstrated by using oligonucleotide sequences of 64 bases associated with human
      papillomavirus (HPV) 16 and 18 L1 genes as model systems. The nonfluorescent
      carboxyl-modified silica NPs were prepared using water-in-oil (W/O) microemulsion
      methods. Avidin was immobilized on the surface of the NPs by covalent binding to
      the carboxyl linkers. The binding capacity of the avidin-covered NPs for ligand
      biotin was quantified and the results show that about 8 avidin molecules are
      bound to one nanoparticle. The silica nano-platforms were prepared through the
      biotin-avidin interaction and the amounts of capture DNA strands for HPV-16 and
      HPV-18 (C-16 and C-18, respectively) conjugated to the surface of the same NPs
      were measured using fluorescent dye hoechst33258. The calculated result shows
      that the amounts of conjugated C-16 and C-18 on 1mg of NPs (9.2 pmol) are about
      13.5 pmol and 15.5 pmol, respectively. A one-step hybridization reaction was
      performed by mixing the silica nano-platforms, HPV-16 and HPV-18 target DNA (T-16
      and T-18), fluorescein amidite (FAM) or 6-carboxyl-X-rhodamine (Rox) labeled HPV
      16 and HPV-18 probes. The hybrid-conjugated NPs were separated by centrifugation,
      and T-16 and T-18 were detected by measuring fluorescence signals of FAM and Rox
      respectively. The results show linear dependence of the fluorescence intensity on
      target DNA concentration in the range from 0.5 to 9 nM, and the detection limit
      (3sigma) of T-16 and T-18 is 0.17 nM and 0.78 nM, respectively.

PMID- 25059159
TI  - A study on the applicability of zinc acetate impregnated silica substrate in the
      collection of hydrogen sulfide by active sampling.
AB  - A novel substrate for the hydrogen sulfide determination in air was developed
      based on zinc acetate impregnated silica in glass tubes. Collected H2S is
      quantified by ion chromatography after sulfide oxidation to sulfate in an
      alkaline solution of H2O2. Laboratory tests were conducted in controlled
      atmosphere to evaluate uptake rate, linearity, sample stability, influence of
      relative humidity and interfering gases. A pilot study was also conducted in the
      field in order to assess the applicability of the substrate and to understand the
      effect that gases such NO2 and CH4 can have on the efficiency of collection of
      H2S. The new substrate has shown to have several advantages with respect to the
      charcoal substrate, that is the one of choice as reported by National Institute
      of Occupational Safety and Health (NIOSH) method. In particular it does not
      suffer from sulfur background and it is not influenced by interfering gases such
      as NO2 and CH4. 

PMID- 25059160
TI  - Miniaturization in voltammetry: ultratrace element analysis and speciation with
      twenty-fold sample size reduction.
AB  - Voltammetric techniques have emerged as powerful methods for the determination
      and speciation of trace and ultratrace elements without any preconcentration in
      several research fields. Nevertheless, large sample volumes are typically
      required (10 mL), which strongly limits their application and/or the precision of
      the results. In this work, we report a 20-fold reduction in sample size for trace
      and ultratrace elemental determination and speciation by conventional
      voltammetric instrumentation, introducing the lowest amount of sample (0.5 mL) in
      which ultratrace detection has been performed up to now. This goal was achieved
      by a careful design of a new sample holder. Reliable, validated results were
      obtained for the determination of trace/ultratrace elements in rainwater (Cd, Co,
      Cu, Ni, Pb) and seawater (Cu). Moreover, copper speciation in seawater samples
      was consistently determined by competitive ligand equilibration-cathodic
      stripping voltammetry (CLE-CSV). The proposed apparatus showed several
      advantages: (1) 20-fold reduction in sample volume (the sample size is lowered
      from 120 to 6 mL for the CLE-CSV procedure); (2) decrease in analysis time due to
      the reduction in purging time up to 2.5 fold; (3) 20-fold drop in reagent
      consumption. Moreover, the analytical performances were not affected: similar
      detection capabilities, precision and accuracy were obtained. Application to
      sample of limited availability (e.g. porewaters, snow, rainwater, open ocean
      water, biological samples) and to the description of high resolution temporal
      trends may be easily foreseen.

PMID- 25059161
TI  - A polypyridyl-pyrene based off-on Cd2+ fluorescent sensor for aqueous phase
      analysis and living cell imaging.
AB  - By retaining the quadrapyridyl receptor of polypyridylhexaazatriphenylene (a
      Cd(2+) sensor reported by us) and extending its chromophoric group with pyrene, a
      chemical sensor (1) was designed and synthesized in this work. This sensor
      exhibit selective off-on fluorescence response to Cd(2+) over other metal ions,
      and the detection limit is as low as 0.02 MUM. The Cd(2+) sensing of 1 has high
      water toleration and can be carried out in the media with the water content up to
      70%. Additionally, 1 was successfully applied to the in vivo imaging of
      intracellular Cd(2+) in living HaLa cells, and showed low cytotoxicity and cell
      membrane permeability in these experiments. These results suggest that 1 has
      potential application in the Cd(2+) analysis of environmental and biological
      samples.

PMID- 25059162
TI  - Practical procedure for discriminating monofloral honey with a broad pollen
      profile variability using an electronic tongue.
AB  - Colour and floral origin are key parameters that may influence the honey market.
      Monofloral light honey are more demanded by consumers, mainly due to their
      flavour, being more valuable for producers due to their higher price when
      compared to darker honey. The latter usually have a high anti-oxidant content
      that increases their healthy potential. This work showed that it is possible to
      correctly classify monofloral honey with a high variability in floral origin with
      a potentiometric electronic tongue after making a preliminary selection of honey
      according their colours: white, amber and dark honey. The results showed that the
      device had a very satisfactory sensitivity towards floral origin (Castanea sp.,
      Echium sp., Erica sp., Lavandula sp., Prunus sp. and Rubus sp.), allowing a leave
      one-out cross validation correct classification of 100%. Therefore, the E-tongue
      shows potential to be used at analytical laboratory level for honey samples
      classification according to market and quality parameters, as a practical tool
      for ensuring monofloral honey authenticity. 

PMID- 25059163
TI  - Detection of metronidazole and ronidazole from environmental samples by surface
      enhanced Raman spectroscopy.
AB  - In this study, the surface enhanced Raman spectra (SERS) of two prohibited
      veterinary drugs, metronidazole (MNZ) and ronidazole (RNZ), have been acquired,
      and compared to the theoretically calculated spectra using density function
      theory (DFT). The experimental Raman and SERS spectra of MNZ and RNZ exhibit high
      resemblance with the DFT calculations. SERS detection of MNZ and RNZ from
      standard solutions as well as real environmental samples (tap, lake, swamp waters
      and soil) was performed on highly sensitive and reproducible silver nanorod array
      substrates. The limits of detection for MNZ and RNZ are 10 and 1 ug/mL in
      methanol and ultra-pure water, respectively, and 10-50 ug/mL in the environmental
      samples. The SERS-based method demonstrates its potential as a rapid, simple, and
      inexpensive means for the onsite screening of banned antibiotics from the aquatic
      and sediment environments, with minimal requirement for sample pretreatment.

PMID- 25059164
TI  - Determination of carbamates in edible vegetable oils by ultra-high performance
      liquid chromatography-tandem mass spectrometry using a new clean-up based on
      zirconia for QuEChERS methodology.
AB  - In this study a fast, selective and sensitive multiresidue method based on
      QuEChERS methodology has been evaluated and validated for the determination of
      carbamate pesticides, in edible vegetable oils by UHPLC-MS/MS. A new clean-up
      sorbent, Supel(TM) QuE Z-Sep(+), has been successfully applied in vegetable oil
      extracts. Z-Sep(+) was compared with other sorbents (i.e. mixture of C18 and PSA)
      previously used for dispersive solid phase extraction of these matrices, reducing
      more effectively matrix effects without a significant decrease of analyte
      recoveries. Matrix effect was studied in different matrices (extra-virgin olive,
      sunflower, maize, linseed and sesame oil) being <=?30?% for most of the studied
      pesticides. Under optimum conditions, recoveries ranged from 74% to 101%, with
      relative standard deviations lower than 10%. Limits of quantification ranged from
      0.09 to 2.0 ug kg(-1), allowing their determination at the low concentration
      levels demanding by current legislation.

PMID- 25059165
TI  - A one-tube multiplexed colorimetric strategy based on plasmonic nanoparticles
      combined with non-negative matrix factorization.
AB  - Herein, a one-tube colorimetric platform has been developed for the simultaneous
      determination of two analytes (DNA as model object) in one tube with picomolar
      sensitivity. SPR-active nanoparticles are used to encode reporter probes
      sensitive to oligonucleotides associated with hepatitis A virus Vall7 polyprotein
      gene (HVA) and hepatitis B virus surface-antigen gene (HVB) respectively and
      magnetic beads (MBs) serve as the removal tool. In this mixed nanoparticles based
      biosensor, the addition of target analytes could change the concentration of each
      nanoparticle, leading to different colors of the supernatant. The influence of
      spectral overlap has been eliminated by a non-negative matrix factorization
      (NMF). With the assistance of NMF, the limit of detection (LOD) can be
      determinated as pM level without amplification. On the whole, this nanosensor
      boasts the advantages of high sensitivity and low sample consumption.
      Simultaneous colorimetric detection and quantification of two molecules in one
      tube are demonstrated. 

PMID- 25059166
TI  - Facile synthesis of multifunctional multi-walled carbon nanotube for pathogen
      Vibrio alginolyticus detection in fishery and environmental samples.
AB  - Interest in carbon nanotubes for detecting the presence of pathogens arises
      because of developments in chemical vapor deposition synthesis and progresses in
      biomolecular modification. Here we reported the facile synthesis of multi-walled
      carbon nanotubes (MWCNTs), which functioned as immuno-, magnetic, fluorescent
      sensors in detecting Vibrio alginolyticus (Va). The structures and properties of
      functionalized MWCNTs were characterized by ultraviolet (UV), Fourier transform
      infrared spectra (FT-IR), X-ray diffraction (XRD), vibrating sample magnetometer
      (VSM), magnetic property measurement system (MPMS) and fluorescent spectra (FL).
      It was found that the functionalized MWCNTs showed: (1) low nonspecific
      adsorption for antibody-antigen, (2) strong interaction with antibody, and (3)
      high immune-magnetic activity for pathogenic cells. Further investigations
      revealed a strong positive linear relationship (R=0.9912) between the
      fluorescence intensity and the concentration of Va in the range of 9.0 * 10(2) to
      1.5 * 10(6) cfum L(-1). Moreover, the relative standard deviation for 11
      replicate detections of 1.0 * 10(4) cfum L(-1) Va was 2.4%, and no cross-reaction
      with the other four strains was found, indicating a good specificity for Va
      detection. These results demonstrated the remarkable advantages of the
      multifunctional MWCNTs, which offer great potential for the rapid, sensitive and
      quantitative detection of Va in fishery and environmental samples.

PMID- 25059167
TI  - HPLC determination of serum pteridine pattern as biomarkers.
AB  - Pteridinic derivatives are important biomolecules considered as biomarkers for
      several diseases, especially in cancer and infectious pathologies. A new
      fluorimetric-HPLC method for the analysis of nine pteridines in human serum has
      been reported. Two analytical columns composed by C18 porous and fused core
      particles were assayed and the results compared. Fused core particle column
      allows us adequate separation, in only one run and in 15 min. Acid precipitation
      step of the proteins and clean-up process with an Isolute ENV+ (hydroxylated
      polystyrene-divinylbenzene copolymer) cartridge of the serum samples have been
      optimized. Analytes were determined by fluorimetric detection, exciting at 272 nm
      and measuring the fluorescence emission at 410 nm for isoxanthopterin, at 465 nm
      for xanthopterin, and at 445 nm for the analysis of the other pteridines.
      Detection limits between 0.07 and 0.61 ng mL(-1) were calculated according to
      Clayton criterium. Intraday precision varied from 1.2 to 5.3 and interday
      precision between 1.2 and 7.4, both expressed as RSD (%). External standard and
      standard addition calibrations were compared in the analysis of serum samples.
      The pteridine amounts in serum (expressed as ng mL(-1) +/- confidence interval)
      were 3.69 +/- 1.78; 1.35 +/- 0.24; 0.46 +/- 0.14; 0.54 +/- 0.24; 0.84 +/- 0.55;
      2.10 +/- 0.51 and 0.23 +/- 0.11 for XAN, NEO, MON, ISO, BIO and 6HMPT,
      respectively, using the external standard method. Comparable results were
      obtained by the standard addition method. It is noticeable that 7BIO was not
      detected in the healthy serum samples analyzed.

PMID- 25059168
TI  - Dual fluorescence resonance energy transfer assay between tunable upconversion
      nanoparticles and controlled gold nanoparticles for the simultaneous detection of
      Pb2+ and Hg2+.
AB  - In this work, we presented a novel dual fluorescence resonance energy transfer
      (FRET) system for the simultaneous detection of Pb(2+) and Hg(2+). This system
      employed two color upconversion nanoparticles (UCNPs) as the donors, and
      controlled gold nanoparticles (AuNPs) as the acceptors. The two donor-acceptor
      pairs were fabricated by hybridizing the aptamers and their corresponding
      complementary DNA. Thus, the green and red upconversion fluorescence could be
      quenched because of a good overlap between the UCNPs fluorescence emission and
      the AuNPs absorption spectrum. In the presence of Pb(2+) and Hg(2+), the aptamers
      preferred to bind to their corresponding analytes and formed a G-quadruplexes
      structure for Pb(2+) and the hairpin-like structure for Hg(2+). As a result, the
      dual FRET was disrupted, and the green and red upconversion fluorescence was
      restored. Under optimized experimental conditions, the relative fluorescence
      intensity increased as the metal ion concentrations were increased, allowing for
      the quantification of Pb(2+) and Hg(2+). The relationships between the
      fluorescence intensity and plotting logarithms of ion concentrations were linear
      in the range from 0.1 to 100 nM for Pb(2+) and 0.5 to 500 nM for Hg(2+), and the
      detection limits of Pb(2+) and Hg(2+) were 50 pM and 150 pM, respectively. As a
      practical application, the aptasensor was used to monitor Pb(2+) and Hg(2+)
      levels in naturally contaminated samples and human serum samples. Ultimately,
      this type of dual FRET could be used to detect other metal ions or contaminants
      in food safety analysis and environment monitoring.

PMID- 25059169
TI  - Trace metal determination in natural waters by automated solid phase extraction
      system and ICP-MS: the influence of low level Mg and Ca.
AB  - A fully automated high pressure pretreatment system with Nobias Chelate-PA1 resin
      (PA1) was developed for trace metal determination by ICP-MS in natural waters. By
      varying the concentrations of Mg and Ca to mimic the concentrations in the eluate
      obtained by PA1 or iminodiacetate type resins, the overall analytical performance
      of the system was assessed for the determination of Al, V, Cr, Mn, Fe, Co, Ni,
      Cu, Zn, Y, Cd, Ag, Pb and REE. Comparing with the low mM level Mg and Ca (both
      ranging from 1 to 4mM) eluted by iminodiacetate type resins, the eluate obtained
      by PA1 contains sub-MUM level Mg and Ca, which remarkably decrease matrix effect
      in ICP-MS analysis and significantly improve the analytical performance. With
      recovery better than 90% for most the trace metals examined, the accuracy was
      further verified through the analysis of five natural water reference materials
      with salinity spanning from 0 to 350/00. We have successfully applied the
      pretreatment system to determine trace metals in the seawater samples collected
      in the Western Philippine Sea through Taiwan GEOTRACES cruise.

PMID- 25059170
TI  - Liquid-phase extraction coupled with metal-organic frameworks-based dispersive
      solid phase extraction of herbicides in peanuts.
AB  - Liquid-phase extraction coupled with metal-organic frameworks-based dispersive
      solid phase extraction was developed and applied to the extraction of pesticides
      in high fatty matrices. The herbicides were ultrasonically extracted from peanut
      using ethyl acetate as extraction solvent. The separation of the analytes from a
      large amount of co-extractive fat was achieved by dispersive solid-phase
      extraction using MIL-101(Cr) as sorbent. In this step, the analytes were adsorbed
      on MIL-101(Cr) and the fat remained in bulk. The herbicides were separated and
      determined by high-performance liquid chromatography. The experimental
      parameters, including type and volume of extraction solvent, ultrasonication
      time, volume of hexane and eluting solvent, amount of MIL-101(Cr) and dispersive
      solid phase extraction time, were optimized. The limits of detection for
      herbicides range from 0.98 to 1.9 MUg/kg. The recoveries of the herbicides are in
      the range of 89.5-102.7% and relative standard deviations are equal or lower than
      7.0%. The proposed method is simple, effective and suitable for treatment of the
      samples containing high content of fat.

PMID- 25059171
TI  - Development of a selective and pH-independent method for the analysis of ultra
      trace amounts of nitrite in environmental water samples after dispersive magnetic
      solid phase extraction by spectrofluorimetry.
AB  - This paper describes an innovative and rapidly dispersive magnetic solid phase
      extraction spectrofluorimetry (DMSPE-FL) method for the analysis of trace amounts
      of nitrite in some environmental water samples. The method includes
      derivatization of aqueous nitrite with 2, 3-diaminonaphthalene (DAN), analysis of
      highly fluorescent 2, 3-naphthotriazole (NAT) derivative using spectrofluorimetry
      after DSPME. The novelty of our method is based on forming NAT that was
      independent with the pH-responsive and was adsorbed on MMWCNT by hydrophobic
      attractions in both acidic and basic media. The extraction efficiency of the
      sorbent was investigated by extraction of nitrite. The optimum extraction
      conditions for NO2(-) were obtained as of extraction time, 1.5 min; 10mg sorbent
      from 160 mL of the sample solution, and elution with 1 mL of acetone/KOH. Under
      the optimal conditions, the calibration curves were obtained in the range of 0.1
      80 ug L(-1) (R(2)=0.999) and LOD (S/N=3) was obtained in 34 ng L(-1). Relative
      standard deviations (RSD) were 0.6 % (five replicates at 5 MUg L(-1)). In
      addition, the feasibility of the method was demonstrated with extraction and
      determination of nitrite from some real samples containing tap, mineral, sea,
      rain, snow and ground waters, with the recovery in standard addition to real
      matrix of 94-102 % and RSDs of 1.8-10.6%.

PMID- 25059172
TI  - Fluorescent detection of protein kinase based on positively charged gold
      nanoparticles.
AB  - Herein, we report a fluorometric method for monitoring the activity and
      inhibition of protein kinase based on positively charged gold nanoparticles,
      (+)AuNPs. In this assay, when the cationic substrate peptide (S-peptide) is
      phosphorylated by protein kinase, the resulting negatively charged product
      peptide (P-peptide) will be adsorbed onto (+)AuNPs through electrostatic
      interaction, and the fluorescence of fluorescein isothiocyanate (FITC) on the
      peptide will be quenched by (+)AuNPs. Thus, the fluorescence of solution can
      respond to the activity of protein kinase. The feasibility of this (+)AuNPs-based
      method has been demonstrated by sensitive measurement of the activity of cAMP
      dependent protein kinase (PKA) with a low detection limit (0.5 mU MUL(-1)).
      Furthermore, the system is successfully applied to estimate the IC50 value of PKA
      inhibitor H-89. The fast mix-and-readout detection process as well as the simple
      synthesis of the unmodified (+)AuNPs makes this proposed method a promising
      candidate for simple and cost-effective kinase activity detection and a good
      potential in high-throughput screening of kinase-related drugs.

PMID- 25059174
TI  - Sensitive electrochemical detection of dopamine with a DNA/graphene bi-layer
      modified carbon ionic liquid electrode.
AB  - A DNA and graphene (GR) bi-layer modified carbon ionic liquid electrode (CILE)
      was fabricated by an electrodeposition method. GR nanosheets were
      electrodeposited on the surface of CILE at the potential of -1.3 V and then DNA
      was further deposited at the potential of +0.5 V on GR modified CILE.
      Electrochemical performances of the fabricated DNA/GR/CILE were carefully
      investigated. Then electrochemical behaviors of dopamine (DA) on the modified
      electrode were studied with the calculated electrochemical parameters. Under the
      optimized conditions, a linear relationship between the oxidation peak current
      and the concentration of DA was obtained in the range from 0.1 MUmol/L to 1.0
      mmol/L with a detection limit of 0.027 MUmol/L (3sigma). The modified electrode
      exhibited excellent reproducibility, repeatability, stability, validation and
      robustness for the electrochemical detection of DA. The proposed method was
      further applied to the DA injection solution and human urine samples
      determination with satisfactory results.

PMID- 25059173
TI  - Real-time analysis of self-assembled nucleobases by Venturi easy ambient sonic
      spray ionization mass spectrometry.
AB  - In this study, the real-time analysis of self-assembled nucleobases was employed
      by Venturi easy ambient sonic-spray ionization mass spectrometry (V-EASI-MS).
      With the analysis of three nucleobases including 6-methyluracil (6MU), uracil (U)
      and thymine (T) as examples, different orders of clusters centered with different
      metal ions were recorded in both positive and negative modes. Compared with the
      results obtained by traditional electrospray ionization mass spectrometry (ESI
      MS) under the same condition, more clusters with high orders, such as
      [6MU7+Na](+), [6MU15+2NH4](2+), [6MU10+Na](+), [T7+Na](+), and [T15+2NH4](2+)
      were detected by V-EASI-MS, which demonstrated the soft ionization ability of V
      EASI for studying the non-covalent interaction in a self-assembly process.
      Furthermore, with the injection of K(+) to the system by a syringe pumping, the
      real-time monitoring of the formation of nucleobases clusters was achieved by the
      direct extraction of samples from the system under the Venturi effect. Therefore,
      the effect of cations on the formation of clusters during self-assembly of
      nucleobases was demonstrated, which was in accordance with the reports. Free of
      high voltage, heating or radiation during the ionization, this technique is much
      soft and suitable for obtaining the real-time information of the self-assembly
      system, which also makes it quite convenient for extraction samples from the
      reaction system. This "easy and soft" ionization technique has provided a
      potential pathway for monitoring and controlling the self-assembly processes.

PMID- 25059175
TI  - Evaluation of the multi-element capabilities of collision/reaction cell
      inductively coupled plasma-mass spectrometry in wine analysis.
AB  - This work explores the multi-element capabilities of inductively coupled plasma
      mass spectrometry with collision/reaction cell technology (CCT-ICP-MS) for the
      simultaneous determination of both spectrally interfered and non-interfered
      nuclides in wine samples using a single set of experimental conditions. The
      influence of the cell gas type (i.e. He, He+H2 and He+NH3), cell gas flow rate
      and sample pre-treatment (i.e. water dilution or acid digestion) on the
      background-equivalent concentration (BEC) of several nuclides covering the mass
      range from 7 to 238u has been studied. Results obtained in this work show that,
      operating the collision/reaction cell with a compromise cell gas flow rate (i.e.
      4 mL min(-1)) improves BEC values for interfered nuclides without a significant
      effect on the BECs for non-interfered nuclides, with the exception of the light
      elements Li and Be. Among the different cell gas mixtures tested, the use of He
      or He+H2 is preferred over He+NH3 because NH3 generates new spectral
      interferences. No significant influence of the sample pre-treatment methodology
      (i.e. dilution or digestion) on the multi-element capabilities of CCT-ICP-MS in
      the context of simultaneous analysis of interfered and non-interfered nuclides
      was observed. Nonetheless, sample dilution should be kept at minimum to ensure
      that light nuclides could be quantified in wine. Finally, a direct 5-fold aqueous
      dilution is recommended for the simultaneous trace and ultra-trace determination
      of spectrally interfered and non-interfered elements in wine by means of CCT-ICP
      MS. The use of the CCT is mandatory for interference-free ultra-trace
      determination of Ti and Cr. Only Be could not be determined when using the CCT
      due to a deteriorated limit of detection when compared to conventional ICP-MS.

PMID- 25059176
TI  - Electromembrane extraction of salivary polyamines followed by capillary zone
      electrophoresis with capacitively coupled contactless conductivity detection.
AB  - Electromembrane extraction (EME) as a novel sample preparation technique was
      firstly applied for the purification and enrichment of four polyamines mainly
      present in saliva samples. These four target analytes, putrescine, cadaverine,
      spermidine, and spermine, were directly determined by CZE with capacitively
      coupled contactless conductivity detection (CZE-C(4)D) after EME procedure.
      Several factors affecting extraction efficiency, electrophoretic separation, and
      detection were investigated. Under the optimum conditions, four polyamines were
      baseline separated within 22 min, exhibiting a linear calibration over three
      orders of magnitude (r>0.999); the highest enrichment factor could reach 106-fold
      (for spermidine), and the LODs were in the range of 1.4-7.0 ng mL(-1). The
      proposed EME/CZE-C(4)D method has been successfully applied to analyze human
      saliva samples with recoveries in the range of 78-97%.

PMID- 25059177
TI  - Application of elastic net and infrared spectroscopy in the discrimination
      between defective and non-defective roasted coffees.
AB  - The quality of the coffee beverage is negatively affected by the presence of
      defective coffee beans and its evaluation still relies on highly subjective
      sensory panels. To tackle the problem of subjectivity, sophisticated analytical
      techniques have been developed and have been shown capable of discriminating
      defective from non-defective coffees after roasting. However, these techniques
      are not adequate for routine analysis, for they are laborious (sample
      preparation) and time consuming, and reliable, simpler and faster techniques need
      to be developed for such purpose. Thus, it was the aim of this study to evaluate
      the performance of infrared spectroscopic methods, namely FTIR and NIR, for the
      discrimination of roasted defective and non-defective coffees, employing a novel
      statistical approach. The classification models based on Elastic Net exhibited
      high percentage of correct classification, and the discriminant infrared spectra
      variables extracted provided a good interpretation of the models. The
      discrimination of defective and non-defective beans was associated with main
      chemical descriptors of coffee, such as carbohydrates, proteins/amino acids,
      lipids, caffeine and chlorogenic acids. 

PMID- 25059178
TI  - Molecular imprinted polymer-coated optical fiber sensor for the identification of
      low molecular weight molecules.
AB  - A biomimetic optical probe for detecting low molecular weight molecules (maltol,
      3-hydroxy-2-methyl-4H-pyran-4-one, molecular weight of 126.11 g/mol), was
      designed, fabricated, and characterized. The sensor couples a molecular imprinted
      polymer (MIP) and the Bragg grating refractometry technology into an optical
      fiber. The probe is fabricated first by inscribing tilted grating planes in the
      core of the fiber, and then by photopolymerization to immobilize a maltol
      imprinted MIP on the fiber cladding surface over the Bragg grating. The sensor
      response to the presence of maltol in different media is obtained by spectral
      interrogation of the fiber transmission signal. The results showed that the limit
      of detection of the sensor reached 1 ng/mL in pure water with a sensitivity of
      6.3 * 10(8)pm/M. The selectivity of the sensor against other compounds and its
      reusability were also studied experimentally. Finally, the unambiguous detection
      of concentrations as little as 10nM of maltol in complex media (real food
      samples) by the MIP-coated tilted fiber Bragg grating sensor was demonstrated.

PMID- 25059179
TI  - Selective and eco-friendly method for determination of mercury(II) ions in
      aqueous samples using an on-line AuNPs-PDMS composite microfluidic device/ICP-MS
      system.
AB  - In this study we developed an on-line, eco-friendly, and highly selective method
      using a gold nanoparticle (AuNP)-coated polydimethylsiloxane (PDMS) composite
      microfluidic (MF) chip coupled to inductively coupled plasma mass spectrometry
      (ICP-MS) to separate trace Hg(2+) ions from aqueous samples. Because Hg(2+) ions
      interact with AuNPs to form Hg-Au complexes, we were able to separate Hg(2+) ions
      from aqueous samples. We prepared the AuNPs-PDMS composite through in situ
      synthesis using a PDMS cross-linking agent to both reduce and embed AuNPs onto
      PDMS microchannels so that no additional reductants were required for either AuNP
      synthesis or the PDMS surface modification (2% HAuCl4, room temperature, 48 h).
      To optimize the proposed on-line system, we investigated several factors that
      influenced the separation of Hg(2+) ions in the AuNPs-PDMS/MF, including
      adsorption pH, adsorption and elution flow rates, microchannel length, and
      interferences from coexisting ions. Under optimized conditions (pH 6.0;
      adsorption/elution flow rates: 0.05/0.5 mL min(-1); channel length: 840 mm), we
      evaluated the accuracy of the system using a standard addition method; the
      measured values had agreements of >= 93.0% with certified values obtained for
      Hg(2+) ions. The relative standard deviations of the proposed method ranged from
      2.24% to 6.21%. The limit of detection for Hg(2+) for the proposed on-line AuNPs
      PDMS/MF/ICP-MS analytical method was as low as 0.07 ug L(-1).

PMID- 25059180
TI  - Evanescent-field-induced Raman scattering for bio-friendly fingerprinting at sub
      cellular dimension.
AB  - Evanescent field induced chemical imaging concept has been realized in analytical
      platform based on the u-tip-enhanced Raman scattering spectroscopy (u-TERS). The
      technique aimed to minimize thermal decomposition of dried biological sample as
      the result of huge concentration of optical field near the tip by increasing the
      size of an aperture-less "excitation source". u-TERS technique is similar to
      classical biosensor systems based on propagating surface plasmon resonance
      phenomenon but with sensitive elements a few micrometers in size that can be
      targeted to the area of interest. The utility of the concept is exemplified by
      the analysis of dried single cell envelope of genetically modified Saccharomyces
      cerevisiae yeast cells, which do not have any heat-removing pathways, by water as
      in the case of the living cell. Practical excitation conditions effective for u
      TERS Raman observation of single layer dried biological samples without
      photodamage-related spectral distortion have been determined - the allowable
      limit is above 30s at 13 uW/um(2). Finally, potential of u-TERS spectroscopy as
      new bio-friendly instrumental platform for chemical fingerprinting and analytical
      characterization of buried nanoscale features is discussed.

PMID- 25059181
TI  - Electrochemical sensing of iron (III) by using rhodamine dimer as an
      electroactive material.
AB  - The voltammetric and potentiometric sensors based on a novel electroactive
      rhodamine dimer (RD) have been developed for the determination of Fe (III) ions.
      The RD exhibits two anodic peaks at 0.5 V and 0.7 V vs. Ag/Ag(+) within the
      potential range of 0.2-1.2V, which on addition of Fe (III) ions get converted to
      single anodic peak with a shift toward more positive potential of 0.9 V vs.
      Ag/Ag(+) due to the formation of Fe (III)-RD complex. The voltammetric sensor has
      been found to work well in the concentration range of 1.5 * 10(-5)-3.5 * 10(-4)M
      with the detection limit of 3.3 * 10(-6)M. Further, the potentiometric response
      of proposed PVC based solid contact coated graphite electrode (CGE-1) was linear
      for Fe (III) ions in the concentration range of 1.0 * 10(-1)-1.0 * 10(-7)M. The
      electrode showed a slope of 18.8 mV/decade with a detection limit of 4.68 * 10(
      8)M for Fe (III) ions. Both of the sensors revealed good selectivity towards Fe
      (III) ions in comparison to various diverse metal ions. The analytical utility of
      the proposed sensors has been confirmed by the estimation of the Fe (III) content
      in different sample matrices.

PMID- 25059182
TI  - Voltammetric aptasensor combined with magnetic beads assay developed for
      detection of human activated protein C.
AB  - A sensitive and selective label free voltammetric aptasensor based on magnetic
      beads assay was performed for the first time in our study for monitoring of human
      activated protein C (APC), which is a serine protease (i.e., key enzyme of the
      protein C pathway). An amino modified DNA aptamer (DNA APT) was covalently
      immobilized onto the surface of carboxylated magnetic beads (MBs), and then, the
      specific interaction between DNA APT and its cognate protein, APC, was performed
      at the surface of MBs. Similarly a biotinylated DNA APT was immobilized onto the
      surface of streptavidin coated MBs. Before and after interaction process, the
      oxidation signal of guanine was measured at disposable pencil graphite electrode
      (PGE) surface in combination with differential pulse voltammetry (DPV) technique
      and accordingly, the decrease at the guanine signal was evaluated. The
      biomolecular recognition of APC was successfully achieved with a low detection
      limit found as 2.35 ug mL(-1) by using MB-COOH based assay. Moreover, the
      selectivity of this aptasensor assay was tested in the presence of numerous
      proteins and other biomolecules: protein C (PC), thrombin (THR), bovine serum
      albumin (BSA), factor Va (FVa) and chromogenic substrate (KS).

PMID- 25059183
TI  - Indirect competitive enzyme-linked immunosorbent assay of tris-(2,3
      dibromopropyl) isocyanurate with monoclonal antibody.
AB  - Tris-(2,3-dibromopropyl) isocyanurate (TBC) is a heterocyclic brominated flame
      retardant and posses typical characteristic of Persistent Organic Pollutants
      (POPs). To meet the need for rapid and reliable monitoring of TBC, a monoclonal
      antibody was produced and an indirect competitive enzyme-linked immunosorbent
      assay (IC-ELISA) was developed based on the monoclonal antibody. Monoclonal
      antibody against TBC was generated using synthesized haptens in mice. After
      optimization of the immunoassay conditions, results showed that the IC50 and the
      limit of detection (LOD) were 1.59 and 0.06 ug/L, respectively. The monoclonal
      antibody shows high specificity and the developed IC-ELISA is with high
      recoveries. The precision investigation indicated that the intra-assay precision
      values were all below 9.2% and that the inter-assay precision values ranged from
      6.7 to 11.3%. The assay of real samples gives results basically consistent with
      UHPLC-MS/MS. The obtained results showed that this proposed immunoassay is a
      potential method for rapid and reliable monitoring of TBC.

PMID- 25059184
TI  - G-quadruplex DNA biosensor for sensitive visible detection of genetically
      modified food.
AB  - In this paper, a novel label-free G-quadruplex DNAzyme sensor has been proposed
      for colorimetric identification of GMO using CaMV 35S promoter sequence as the
      target. The binary probes can fold into G-quadruplex structure in the presence of
      DNA-T (Target DNA) and then combine with hemin to form a DNAzyme resembling
      horseradish peroxidase. The detection system consists of two G-rich probes with
      2:2 split mode by using the absorbance and color of ABTS(2-) as signal reporter.
      Upon the addition of a target sequence, two probes both hybridize with target and
      then their G-rich sequences combine to form a G-quadruplex DNAzyme, and the
      DNAzyme can catalyze the reaction of ABTS(2-) with H2O2. Then the linear range is
      from 0.05 to 0.5 MUM while detection limit is 5nM. These results demonstrate that
      the proposed G-quadruplex DNAzyme method could be used as a simple, sensitive and
      cost-effective approach for assays of GMO.

PMID- 25059185
TI  - Application of third-order multivariate calibration algorithms to the
      determination of carbaryl, naphthol and propoxur by kinetic spectroscopic
      measurements.
AB  - In the present work a new application of third-order multivariate calibration
      algorithms is presented, in order to quantify carbaryl, naphthol and propoxur
      using kinetic spectroscopic data. The time evolution of fluorescence data
      matrices was measured, in order to follow the alkaline hydrolysis of the
      pesticides mentioned above. This experimental system has the additional
      complexity that one of the analytes is the reaction product of another analyte,
      and this fact generates linear dependency problems between concentration
      profiles. The data were analyzed by three different methods: parallel factor
      analysis (PARAFAC), unfolded partial least-squares (U-PLS) and multi-dimensional
      partial least-squares (N-PLS); these last two methods were assisted with residual
      trilinearization (RTL) to model the presence of unexpected signals not included
      in the calibration step. The ability of the different algorithms to predict
      analyte concentrations was checked with validation samples. Samples with
      unexpected components, tiabendazole and carbendazim, were prepared and spiked
      water samples of a natural stream were used to check the recovered
      concentrations. The best results were obtained with U-PLS/RTL and N-PLS/RTL with
      an average of the limits of detection of 0.035 for carbaryl, 0.025 for naphthol
      and 0.090 for propoxur (mg L(-1)), because these two methods are more flexible
      regarding the structure of the data.

PMID- 25059186
TI  - Novel methoxypropylimmidazolium beta-cyclodextrin for improved enantioseparation
      of amino acids.
AB  - A new single-isomer cationic cyclodextrin, mono-6(A)-[3-(3-methoxypropyl)imidazol
      1-ium]-6(A)-beta-cyclodextrin chloride, has been synthesized and successfully
      used for the chiral separation of dansyl amino acids in capillary
      electrophoresis. With methoxy functionality, the new cationic cyclodextrin
      exhibits significantly improved enantioselectivities. Excellent
      enantioseparations for amino acids are obtained in chiral selector concentration
      range between 2.5mM to 15 mM at pH 6.0. Chiral resolution as high as 7.3 was
      achieved for Dns-Aca with 5mM chiral selector. Comparison study and theoretical
      calculation with Wren's model attribute the enhanced enantioseparation to the
      stronger inclusion complexation between amino acids and cyclodextrin. The binding
      constants for dansyl amino acids and the cationic cyclodextrins are calculated to
      be 173-253 M(-1), while the optimum cyclodextrin concentrations were estimated to
      be 4.1-7.6 mM.

PMID- 25059187
TI  - Determination of arsenic speciation in sulfidic waters by Ion Chromatography
      Hydride-Generation Atomic Fluorescence Spectrometry (IC-HG-AFS).
AB  - A method for the analysis of arsenic species in aqueous sulfide samples is
      presented. The method uses an ion chromatography system connected with a Hydride
      Generation Atomic Fluorescence Spectrometer (IC-HG-AFS). With this method
      inorganic As(III) and As(V) species in water samples can be analyzed, including
      arsenite (HnAs(III)O3(n-3)), thioarsenite (HnAs(III)S3(n-3)), arsenate
      (HnAs(V)O4(n-3)), monothioarsenate (HnAs(V)SO3(n-3)), dithioarsenate
      (HnAs(V)S2O2(n-3)), trithioarsenate (HnAs(V)S3O(n-3)) and tetrathioarsenate
      (HnAs(V)S4(n-3)). The peak identification and retention times were determined
      based on standard analysis of the various arsenic compounds. The analytical
      detection limit was ~1-3 ug L(-1) (LOD), depending on the quality of the
      baseline. This low detection limit makes this method also applicable to
      discriminate between waters meeting the drinking water standard of max. 10 ug L(
      1) As, and waters that do not meet this standard. The new method was successfully
      applied for on-site determination of arsenic species in natural sulfidic waters,
      in which seven species were unambiguously identified.

PMID- 25059188
TI  - Affinity chemiresistor sensor for sugars.
AB  - In this work, a non-enzymatic chemiresistive sugar sensor has been developed by
      combining a synthetic receptor with aligned single-walled carbon nanotubes
      (SWNTs) device. Briefly, boronic acid as a multivalent sugar receptor was
      immobilized on carbon nanotubes through amide bond formation. The interaction
      between three common sugars (d-glucose, d-fructose and sucrose) and boronic acid
      modified SWNTs device was studied. The effect of pH on the receptor-ligand
      binding was examined and highest response was observed at pH 9. The
      chemiresistive sensor exhibited specific and reproducible detection with
      sensitivity over the concentration range of 1-20mM, 1-25 mM, and 1-30 mM for
      fructose, glucose, and sucrose, respectively. The sensor showed no interference
      from common electroactive compounds such as citric acid, uric acid, and ascorbic
      acid. Furthermore, the sensor retained 97.4% of the initial value after five
      regeneration cycles with an acidic buffer at pH 5, thus ensuring good
      reusability.

PMID- 25059189
TI  - Energy-dispersive X-ray spectrometry combined with directly suspended droplet
      microextraction for determination of dissolved silicate in surface water via
      silicomolybdenum blue complex.
AB  - Energy-dispersive X-ray fluorescence spectrometry (EDXRF) is a well-established
      analytical technique successfully applied with good precision and accuracy to
      determination of many elements. However, in the case of elements of low atomic
      number, such as silicon, direct determination is hampered due to low fluorescence
      yield and relatively low energy easily absorbed by sample matrix. An indirect
      method for determining surface water silicate is thus proposed. The method is
      based on silicate determination via molybdenum present in silicomolybdenum blue
      complex. Determination follows directly suspended droplet microextraction.
      Optimum conditions for both microextraction and EDXRF measurement were studied. A
      good ratio of silicon to molybdenum (1-41) and a sensitive Kalpha line of
      molybdenum make it possible to determine low concentrations of silicate. Under
      optimized conditions, good linearity, up to 3 MUg mL(-1) (r=0.9990), and good
      detection limit (6 ng mL(-1)) were achieved. The total RSD for the EDXRF
      determination of silicate following DSDME was 6.7%. Taking into account all steps
      preceding the determination and the uncertainty of XRF measurements, the proposed
      method can be recognized as precise. The enrichment factor was 140. The developed
      method was used to determine dissolved silicate content in surface water samples.
      The accuracy and repeatability of the proposed procedure were checked by standard
      addition method and compared to the results obtained using ICP-OES technique. The
      recovery (92.2-96%) was satisfactory and indicates usefulness of the developed
      procedure.

PMID- 25059190
TI  - Microextraction of non-steroidal anti-inflammatory drugs from waste water samples
      by rotating-disk sorptive extraction.
AB  - In this study, six non-steroidal anti-inflammatory drugs (NSAIDs) were extracted
      from water samples using the rotating-disk sorptive extraction (RDSE) technique.
      The extraction disk device contains a central cavity that allows for the
      incorporation of a powdered sorbent phase (OasisTM HLB). The analytes were
      extracted from water and pre-concentrated on the sorbent to reach the extraction
      equilibrium, and then they were desorbed with solvent, derivatized and determined
      by gas chromatography-mass spectrometry (GC-MS). The variables for the extraction
      were studied using high performance liquid chromatography with a diode array
      detector (HPLC-DAD) to avoid the derivatization step, and the optimum values were
      as follows: 60 mg of OasisTM HLB, a rotation velocity of 3,000 rpm, a pH of 2, a
      sample volume of 50 mL, and an extraction time of approximately 90-100 min. The
      recoveries ranged from 71 to 104%, with relative standard deviations (RSD)
      between 2 and 8%. The detection limits ranged from 0.001 to 0.033 ug L(-1). The
      described method was applied to the analysis of influents and effluents from
      wastewater treatment plants (WWTP) in Santiago, Chile. The concentrations of the
      detected drugs ranged from 1.5 to 13.4 ug L(-1) and from 1.0 to 3.2 ug L(-1) in
      the influents and effluents, respectively. The samples were extracted by solid
      phase extraction (SPE). No significant differences were observed in the
      determined concentrations for most of the NSAIDs, indicating that RDSE is an
      alternative method for the preparation of water samples.

PMID- 25059191
TI  - A novel dispersive micro solid phase extraction using zein nanoparticles as the
      sorbent combined with headspace solid phase micro-extraction to determine
      chlorophenols in water and honey samples by GC-ECD.
AB  - This study presents a new technique, dispersive micro solid phase extraction
      (DMSPE) combined with headspace solid phase micro-extraction (HS-SPME) for
      extraction and determination of chlorophenols (CPs) in water and honey samples
      using a Gas Chromatography-Electron Capture Detector (GC-ECD). Zein nanoparticles
      were made by liquid-liquid dispersion and applied for the first time as the
      sorbent phase in DMSPE. In the proposed DMSPE-HS-SPME method, 1% w/v of ethanolic
      zein solution was added to an aqueous sample and then a dose of the in-situ
      generated zein nanoparticles was applied to a pre-concentration of target
      analytes. Thermal desorption of analytes was performed after the isolating
      sorbent phase, and then HS-SPME was applied for enrichment prior to introducing
      to gas chromatography. All the important parameters influencing efficiency of the
      extraction process such effects of salt, pH, sorbent concentration, temperature,
      sorbent solution volume in DMSPE procedure, extraction temperature, extraction
      time, desorption temperature and time in the HS-SPME procedure were investigated
      and optimized. Results showed that under optimum extraction conditions, detection
      limits (signal to noise ratio=3) were in the range of 0.08-0.6 ng mL(-1) and
      evaluations for relative standard deviations (RSDs %) were between 6.62% and
      8.36%.

PMID- 25059192
TI  - Separation of Gd-humic complexes and Gd-based magnetic resonance imaging contrast
      agent in river water with QAE-Sephadex A-25 for the fractionation analysis.
AB  - Gadolinium complexed with naturally occurring, negatively charged humic
      substances (humic and fulvic acids) was collected from 500 mL of sample solution
      onto a column packed with 150 mg of a strongly basic anion-exchanger (QAE
      Sephadex A-25). A Gd-based magnetic resonance imaging contrast agent
      (diethylenetriamine-N,N,N',N",N"-pentaacetato aquo gadolinium(III), Gd-DTPA(2-))
      was simultaneously collected on the same column. The Gd-DTPA complex was desorbed
      by anion-exchange with 50mM tetramethylammonium sulfate, leaving the Gd-humic
      complexes on the column. The Gd-humic complexes were subsequently dissociated
      with 1M nitric acid to desorb the humic fraction of Gd. The two-step desorption
      with small volumes of the eluting agents allowed the 100-fold preconcentration
      for the fractionation analysis of Gd at low ng L(-1) levels by inductively
      coupled plasma-mass spectrometry (ICP-MS). On the other hand, Gd(III) neither
      complexed with humic substances nor DTPA, i.e., free species, was not sorbed on
      the column. The free Gd in the effluent was preconcentrated 100-fold by a
      conventional solid-phase extraction with an iminodiacetic acid-type chelating
      resin and determined by ICP-MS. The proposed analytical fractionation method was
      applied to river water samples.

PMID- 25059193
TI  - A thiophene-modified screen printed electrode for detection of dengue virus NS1
      protein.
AB  - A thiophene-modified screen printed electrode (SPE) for detection of the Dengue
      virus non-structural protein 1 (NS1), an important marker for acute phase
      diagnosis, is described. A sulfur-containing heterocyclic compound, the thiophene
      was incorporated to a carbon ink to prepare reproducible screen printed
      electrodes. After cured, the thiophene SPE was coated by gold nanoparticles
      conjugated to Protein A to form a nanostrutured surface. The Anti-NS1 antibodies
      immobilized via their Fc portions via Protein A, leaving their antigen specific
      sites free circumventing the problem of a random antibodies immobilization.
      Amperometric responses to the NS1 protein of dengue virus were obtained by cyclic
      voltammetries performed in presence of ferrocyanide/ferricyanide as redox probe.
      The calibration curve of immunosensor showed a linear response from 0.04 ug mL(
      1) to 0.6 ug mL(-1) of NS1 with a good linear correlation (r=0.991, p<0.05). The
      detection limit (0.015 ug mL(-1) NS1) was lower than conventional analytical
      methods. In this work, thiophene monomers incorporated in the carbon ink enhanced
      the electroanalytical properties of the SPEs, increasing their reproducibility
      and sensitivity. This point-of-care testing represents a great potential for use
      in epidemic situations, facilitating the early diagnosis in acute phase of dengue
      virus.

PMID- 25059194
TI  - A rapid, automated gradient flow injection-spectrophotometric technique for study
      of metal complexation reactions.
AB  - Controlled dispersion as generated in flow injection analysis (FIA) essentially
      permits an infinite variety of known compositional gradients. Using this unique
      advantage of FIA, the stability constants of metal complexation are calculated by
      injecting an aliquot of metal solution into the flow of ligand solution in a
      single-line manifold. While the ligand dilution is negligible, the concentration
      gradient of injected metal ion can be calculated from the dispersion pattern
      which is calibrated previously using a dye solution. To show the simplicity,
      versatility and ease of instrumental setup over approaches based on the classical
      titration, the method was applied to determine stability constants of murexide
      with several metal ions. The SQUAD computer program was used for fitting the
      predefined complexation model to the spectral-mole ratio data. The proper
      selection of the chemical model was verified by the determination of the number
      of absorbing species by using a singular value decomposition of each data set.
      The stability constants obtained for murexide and metals including Cu(2+),Cd(2+),
      Pb(2+), Ca(2+) and Co(2+) are 4.35, 4.27, 4.50, 2.55 and 2.57, respectively. The
      formation constants determined here are in good agreement with those previously
      reported and with those obtained from conventional batch titrations. The main
      advantage over the classical batch titration method is that by utilizing just one
      injection per sample, the proposed method reduces experimental error by reducing
      the experimental steps needed to obtain the required spectral-mole ratio data.
      The details of the proposed method are discussed. 

PMID- 25059195
TI  - A high-performance direct transmethylation method for total fatty acids
      assessment in biological and foodstuff samples.
AB  - Isolation is the main bottleneck in the analysis of fatty acids in biological
      samples and foods. In the last few decades some methods described direct
      derivatization procedures bypassing these steps. They involve the utilization of
      methanolic HCL or BF3 as catalysts, but several evidences from previous works
      suggest these reagents are unstable, lead to the formation of artifacts and alter
      the distribution of specific compounds as hydroxy fatty acids or CLA. However,
      the main issue is that they are excellent esterification reagents but poor in
      transterification, being not suitable for the analysis of all lipid classes and
      leading to erroneous composition quantitations. The present research work is a
      comprehensive comparison of six general methylation protocols using base, acid or
      base/acid catalysts plus a proposed method in the analysis of total fatty acids
      in lipid standards mixtures, foodstuff and biological samples. The addition of
      aprotic solvents to the reaction mixture to avoid alterations was also tested.
      Results confirmed that procedures solely involving acid catalyst resulted in
      incomplete derivatizations and alteration of the fatty acid profile, partially
      corrected by addition of the aprotic solvent. The proposed method combining
      sodium methoxyde and sulfuric acid showed absence of alteration of the FAME
      profile and the best values for response factors (short chain fatty acids to
      PUFA), accuracy in the determination of total cholesterol and derivatization
      performance, thus showing a high reliability in the determination of the total
      fatty acid composition in biological samples and foods. 

PMID- 25059196
TI  - Analysis of munitions constituents in IMX formulations by HPLC and HPLC-MS.
AB  - The use of Insensitive Munitions eXplosives (IMX) is increasing as the Army seeks
      to replace certain conventional munitions constituents, such as 2,4,6
      trinitrotolene (TNT), for improved safety. The IMX formulations are more stable
      and therefore less prone to accidental detonation while designed to match the
      performance of legacy materials. Two formulations, IMX 101 and 104 are being
      investigated as a replacement for TNT in artillery rounds and composition B Army
      mortars, respectively. The chemical formulations of IMX-101 and 104 are comprised
      of four constituents;2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one
      (NTO), 1-nitroguanidine (NQ), and Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
      which are mixed in various ratios to achieve the desired performance. The current
      work details the analysis of the IMX constituents by single column HPLC-UV-ESI
      MS. Detection limits determined are in agreement with similar HPLC analysis of
      compounds, ranging from 7 to 9MUg/L. Gradient mobile phases are used to allow
      separation of the 4 target compounds in more complex mixture of other concomitant
      compounds. Mass spectra are used to confirm analyte identity with chromatographic
      retention time.

PMID- 25059197
TI  - A systematic review and meta-analysis of factors associated with anthelmintic
      resistance in sheep.
AB  - BACKGROUND: Anthelmintic drugs have been widely used in sheep as a cost-effective
      means for gastro-intestinal nematode (GIN) control. However, growing anthelmintic
      resistance (AHR) has created a compelling need to identify evidence-based
      management recommendations that reduce the risk of further development and impact
      of AHR. OBJECTIVE: To identify, critically assess, and synthesize available data
      from primary research on factors associated with AHR in sheep. METHODS:
      Publications reporting original observational or experimental research on
      selected factors associated with AHR in sheep GINs and published after 1974, were
      identified through two processes. Three electronic databases (PubMed, Agricola,
      CAB) and Web of Science (a collection of databases) were searched for potentially
      relevant publications. Additional publications were identified through
      consultation with experts, manual search of references of included publications
      and conference proceedings, and information solicited from small ruminant
      practitioner list-serves. Two independent investigators screened abstracts for
      relevance. Relevant publications were assessed for risk of systematic bias. Where
      sufficient data were available, random-effects Meta-Analyses (MAs) were performed
      to estimate the pooled Odds Ratio (OR) and 95% Confidence Intervals (CIs) of AHR
      for factors reported in >=2 publications. RESULTS: Of the 1712 abstracts screened
      for eligibility, 131 were deemed relevant for full publication review. Thirty
      publications describing 25 individual studies (15 observational studies, 7
      challenge trials, and 3 controlled trials) were included in the qualitative
      synthesis and assessed for systematic bias. Unclear (i.e. not reported, or unable
      to assess) or high risk of selection bias and confounding bias was found in 93%
      (14/15) and 60% (9/15) of the observational studies, respectively, while unclear
      risk of selection bias was identified in all of the trials. Ten independent
      studies were included in the quantitative synthesis, and MAs were performed for
      five factors. Only high frequency of treatment was a significant risk factor
      (OR=4.39; 95% CI=1.59, 12.14), while the remaining 4 variables were marginally
      significant: mixed-species grazing (OR=1.63; 95% CI=0.66, 4.07); flock size
      (OR=1.02; 95% CI=0.97, 1.07); use of long-acting drug formulations (OR=2.85; 95%
      CI=0.79, 10.24); and drench-and-shift pasture management (OR=4.08; 95% CI=0.75,
      22.16). CONCLUSIONS: While there is abundant literature on the topic of AHR in
      sheep GINs, few studies have explicitly investigated the association between
      putative risk or protective factors and AHR. Consequently, several of the current
      recommendations on parasite management are not evidence-based. Moreover, many of
      the studies included in this review had a high or unclear risk of systematic
      bias, highlighting the need to improve study design and/or reporting of future
      research carried out in this field.

PMID- 25059198
TI  - An economic analysis of hyperketonemia testing and propylene glycol treatment
      strategies in early lactation dairy cattle.
AB  - The purpose was to develop stochastic economic models which address variation in
      disease risks and costs in order to evaluate different simulated on-farm testing
      and propylene glycol (PG) treatment strategies based on herd hyperketonemia (HYK)
      incidence during the first 30 DIM. Data used in model development concerning the
      difference in health and production consequences between HYK and non-ketotic cows
      were based on results from 10 studies representing over 13,000 cows from 833
      dairy farms in North America, Canada, and Europe. Inputs for PG associated
      variables were based on a large field trial using cows from 4 free-stall dairy
      herds (2 in New York and 2 in Wisconsin). Four simulated on-farm testing and
      treatment strategies were analyzed at herd HYK incidences ranging from 5% to 80%
      and included: 1) treating all cows with 5d of PG starting at 5 DIM, 2) testing
      all cows for HYK 1 day per week (e.g. Mondays) from 3 to 16 DIM and treating all
      positive cows with 5d of oral PG, 3) testing all cows for HYK 2 days per week
      (e.g. Mondays and Thursdays) from 3 to 9 DIM and treating all positive cows with
      5d of oral PG, and 4) testing all cows for HYK 3 days per week (e.g. Mondays,
      Wednesdays, and Fridays) from 3 to 16 DIM and treating all positive cows with 5d
      of oral PG. Cost-benefit analysis included the costs associated with labor to
      test cows, beta-hydroxybutyrate test strips, labor to treat cows, PG, and the
      associated gain in milk production, decrease in DA and early removal risks of PG
      treated HYK positive cows compared to non-treated HYK positive cows. Stochastic
      models were developed to account for variability in the distribution of input
      variables. Per 100 fresh cows in a herd with an HYK incidence of 40%, the mean
      economic benefits of the 4 different strategies were $1088, $744, $1166, and
      $760, respectively. Testing cows 2 days per week from 3 to 9 DIM was the most
      cost-effective strategy for herds with HYK incidences between 15% and 50%; above
      50%, treating all fresh cows with 5d of PG was the most cost-effective strategy.
      These results show that for herds similar to those used in model, when herd HYK
      incidences rise above 25%, almost any HYK testing and treatment protocol will be
      economically beneficial for the farm. 

PMID- 25059199
TI  - Contrasting transcriptome landscapes of rabbit pluripotent stem cells in vitro
      and in vivo.
AB  - Pluripotency refers to the ability for a single cell to differentiate into the
      three embryonic germ layers. In mice, two types of pluripotent stem cells with
      different features have been obtained in vitro. Naive pluripotent stem cells are
      derived from the inner cell mass (ICM) of early blastocyst (ESCs) or reprogrammed
      from somatic cells (iPSCs), while primed pluripotent stem cells are derived from
      late epiblast (EpiSCs). Cells in a primed pluripotency state are more prone to
      differentiation and only naive pluripotent stem cells form germline chimera after
      injection into a blastocyst. Despite numerous attempts, capturing pluripotency in
      domestic mammalian species has been largely unsuccessful and only primed
      pluripotent stem cells have been obtained even starting from early blastocyst or
      reprogramming somatic cells. This raises two questions: whether inner cell mass
      and epiblast are in naive or primed pluripotency state and what are the
      transcriptome features of ESCs and iPSCs in these species. To address these
      questions we compared rabbit ICM, epiblast, ESCs and iPSCs transcriptomes. Our
      results show that: (i) molecular signature of naive and primed pluripotency may
      differ between mice and rabbit embryos; (ii) Genes involved in G1/S transition of
      the cell-cycle, actin cytoskeleton signaling, development and differentiation
      pathways are upregulated in ESCs and iPSCs; (iii) ICM and epiblast upregulate
      pluripotency associated genes and display specific metabolic features. These
      results denote an advanced primed state of pluripotency for rabbit ESCs and iPSCs
      and evidence specific functions for ICM and epiblast that are not shared by ESCs
      and iPSCs. 

PMID- 25059200
TI  - Equine chorionic gonadotrophin administration to rams improves their
      effectiveness to stimulate anoestrous ewes (the "ram effect").
AB  - Ewes' response to ram effect is related to the strength of androgen-dependent ram
      signals. Experiment 1 aimed to determine if the administration of a single dose
      of 1000IU of eCG to rams three days before joining them with ewes enhance their
      ability to stimulate females. Based on the results of Experiment 1, in a second
      experiment rams received two doses seven and three days before their introduction
      to females. In Experiment 1, rams treated or not with eCG were joined with ewes,
      and estrous was recorded until Day 5 (Day 0=rams and ewes were joined), and from
      Day 15 to Day 23. In addition, serum testosterone concentration was measured in
      all rams in the first recorded period. Testosterone values were greater in eCG-E1
      than in Con-E1 rams on Days 0 and 2. The percentage of ewes in estrus was similar
      in both groups. In Experiment 2, rams were treated with two doses of eCG on Days 
      7 and -3 or remained as untreated controls. Estrous was recorded until Day 5, and
      pregnancy rate on Day 46; testosterone was measured in samples collected from all
      rams. Testosterone concentration was greater in eCG-E2 than Con-E2 rams from Day 
      5 to Day 1, and tended to do so on Day 2. More eCG-E2 than Con-E2 ewes came into
      estrus and became pregnant. It was concluded that treatment of rams with two high
      doses of eCG before joining them with anestrous ewes, enhanced their ability to
      induce ewes' cyclic activity (the "ram effect").

PMID- 25059201
TI  - The immunoproteasome as a therapeutic target for hematological malignancies.
AB  - Remarkable successes with the FDA-approved proteasome inhibitors bortezomib
      (Velcade((r))) and carfilzomib (Kyprolis((r))) have proved that the proteasome is
      an effective target for the treatment of multiple myeloma. In other hematological
      malignancies, however, clinical trials of proteasome-targeting drugs have shown
      generally disappointing results to date. Additionally, existing proteasome
      inhibitors have significant issues with toxicity, poor response rate, and the
      emergence of resistance for many patients. A new generation of small-molecule
      therapies specifically targeting the immunoproteasome may have the potential to
      overcome the drawbacks of bortezomib and carfilzomib in multiple myeloma and to
      bring significant benefits of proteasome inhibitor therapies to many more
      patients. In this article, we describe the potential of the immunoproteasome as a
      therapeutic target for hematological malignancies and the recent progress in the
      development of useful immunoproteasome inhibitors. 

PMID- 25059202
TI  - The effects of pre-natal-, early-life- and indirectly-initiated exposures to
      maximum adversities on the course of schizophrenia.
AB  - BACKGROUND: The effects of pre-natal-, early-life- and indirectly-initiated
      exposures to protracted maximum adversity on the course of schizophrenia are
      unknown. AIMS: To compare the aforementioned Holocaust directly exposed subgroups
      with an indirectly exposed subgroup on the course of schizophrenia. METHOD: The
      study population were: Israeli Jews in-uterus or born in Nazi-occupied or
      dominated European nations by the end of the persecution of the Jews, who were
      alive in 1950, and who had a last discharge diagnosis of schizophrenia in the
      Israel National Psychiatric Case Registry by 2013 (N=4933). The population was
      disaggregated into subgroups who (1) migrated after WWII and who had (1a) pre
      natal (n=584, 11.8%) and (1b) early-life (n=3709, 75.2%) initiated exposures to
      the maximum adversities of the Holocaust, and (2) indirectly exposed individuals
      to the Holocaust who migrated before the Nazi-era persecution begun (n=640, 13%).
      Recurrent event survival analyses were computed to examine the psychiatric re
      hospitalization risk of the study subgroups, unadjusted and adjusted for age of
      onset of the disorder and sex. RESULTS: The pre-natal initiated exposure subgroup
      had a significantly (p<0.05) greater risk of psychiatric re-hospitalizations for
      schizophrenia than the other subgroups (unadjusted: HR=3.39, 95% CI 2.95, 3.90;
      adjusted: HR=2.28, 2.00, 2.60). This result replicated in sensitivity analyses
      for: Poland-born individuals, the years 1922 and 1935; and followed at least 10
      years and to the year 2000. CONCLUSIONS: Pre-natal initiated exposure to the
      maximal adversity of the holocaust constitutes a consistent risk factor for a
      worse course of schizophrenia, a possible byproduct of neurodevelopment
      disruptions induced by maternal stress and/or famine and/or infections.

PMID- 25059203
TI  - Ameliorating ER-stress attenuates Aeromonas hydrophila-induced mitochondrial
      dysfunctioning and caspase mediated HKM apoptosis in Clarias batrachus.
AB  - Endoplasmic reticulum (ER)-stress and unfolding protein response (UPR) has not
      been implied in Aeromonas hydrophila-pathogenicity. We report increased
      expression of the ER-stress markers: CHOP, BiP and phospho-eIF2alpha in A.
      hydrophila-infected headkidney macrophages (HKM) in Clarias batrachus. Pre
      treatment with ER-stress inhibitor, 4-PBA alleviated ER-stress and HKM apoptosis
      suggesting ER-UPR critical for the process. The ER-Ca(2+) released via inositol
      triphosphate and ryanodine receptors induced calpain-2 mediated superoxide ion
      generation and consequent NF-kappaB activation. Inhibiting NF-kappaB activation
      attenuated NO production suggesting the pro-apoptotic role of NF-kappaB on HKM
      pathology. Calpain-2 activated caspase-12 to intensify the apoptotic cascade
      through mitochondrial-membrane potential (psim) dissipation and caspase-9
      activation. Altered mitochondrial ultra-structure consequent to ER-Ca(2+) uptake
      via uniporters reduced psim and released cytochrome C. Nitric oxide induced the
      cGMP/PKG-dependent activation of caspase-8 and truncated-Bid formation. Both the
      caspases converge onto caspase-3 to execute HKM apoptosis. These findings offer a
      possible molecular explanation for A. hydrophila pathogenicity. 

PMID- 25059204
TI  - Rituximab in combination with corticosteroids for the treatment of anti
      neutrophil cytoplasmic antibody-associated vasculitis: a NICE single technology
      appraisal.
AB  - As part of its single technology appraisal (STA) process, the National Institute
      for Health and Care Excellence (NICE) invited the manufacturer of rituximab
      (Roche Products) to submit evidence of the clinical and cost effectiveness of
      rituximab in combination with corticosteroids for treatment of anti-neutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The School of Health and
      Related Research Technology Appraisal Group at the University of Sheffield was
      commissioned to act as the independent Evidence Review Group (ERG). The ERG
      produced a critical review of the evidence for the clinical and cost
      effectiveness of the technology, based upon the manufacturer's submission to
      NICE. The evidence was derived mainly from a double-blind, phase III, placebo
      controlled trial of rituximab in patients with new or relapsed 'severe' AAV,
      which compared a rituximab treatment regimen with an oral cyclophosphamide
      treatment regimen. Intravenous cyclophosphamide is also commonly used but was not
      included in the pivotal trial. The evidence showed that rituximab is noninferior
      to oral cyclophosphamide in terms of induction of remission in adults with AAV
      and de novo disease, and is superior to oral cyclophosphamide in terms of
      remission in adults who have relapsed once on cyclophosphamide. The ERG concluded
      that the results of the manufacturer's economic evaluation could not be
      considered robust, because of errors and because the full range of relevant
      treatment sequences were not modelled. The ERG amended the manufacturer's model
      and demonstrated that rituximab was likely to represent a cost-effective addition
      to the treatment sequence if given after cyclophosphamide treatment.

PMID- 25059205
TI  - Interventions to reduce medication errors in pediatric intensive care.
AB  - OBJECTIVE: To systematically examine the research literature to identify which
      interventions reduce medication errors in pediatric intensive care units. DATA
      SOURCES: Databases were searched from inception to April 2014. STUDY SELECTION
      AND DATA EXTRACTION: Studies were included if they involved the conduct of an
      intervention with the intent of reducing medication errors. DATA SYNTHESIS: In
      all, 34 relevant articles were identified. Apart from 1 study, all involved
      single-arm, before-and-after designs without a comparative, concurrent control
      group. A total of 6 types of interventions were utilized: computerized physician
      order entry (CPOE), intravenous systems (ISs), modes of education (MEs),
      protocols and guidelines (PGs), pharmacist involvement (PI), and support systems
      for clinical decision making (SSCDs). Statistically significant reductions in
      medication errors were achieved in 7/8 studies for CPOE, 2/5 studies for ISs,
      9/11 studies for MEs, 1/2 studies for PGs, 2/3 studies for PI, and 3/5 studies
      for SSCDs. The test for subgroup differences showed that there was no
      statistically significant difference among the 6 subgroups of interventions,
      chi(2)(5) = 1.88, P = 0.87. The following risk ratio results for meta-analysis
      were obtained: CPOE: 0.47 (95% CI = 0.28, 0.79); IS: 0.37 (95% CI = 0.19, 0.73);
      ME: 0.36 (95% CI = 0.22, 0.58); PG: 0.82 (95% CI = 0.21, 3.25); PI: 0.39 (95% CI
      = 0.10, 1.51), and SSCD: 0.49 (95% CI = 0.23, 1.03). CONCLUSIONS: Available
      evidence suggests some aspects of CPOE with decision support, ME, and IS may help
      in reducing medication errors. Good quality, prospective, observational studies
      are needed for institutions to determine the most effective interventions.

PMID- 25059206
TI  - Rotating cylindrical filters used in perfusion cultures: CFD simulations and
      experiments.
AB  - The particle and fluid dynamics in a rotating cylindrical filtration (RCF) system
      used for animal cell retention in perfusion processes was studied. A validated
      CFD model was used and the results gave numerical evidence of phenomena that had
      been earlier claimed, but not proven for this kind of application under turbulent
      and high mesh permeability conditions, such as bidirectional radial exchange flow
      (EF) through the filter mesh and particle (cells) lateral migration. Taylor
      vortices were shown to cause EF 10-100 times higher than perfusion flow,
      indicating that EF is the main drag source, at least in early stages of RCF
      operation. Particle lateral migration caused a cell concentration reduction (CCR)
      near the filter surface of approximately 10%, contributing significantly to cell
      separation in RCF systems and giving evidence that the mesh sieving effect is not
      the sole phenomenon underlying cell retention in RCF systems. Filter rotation
      rate was shown to significantly affect both EF and CCR. A higher separation
      efficiency (measured experimentally at 2,000-L bioreactor scale) and an enhanced
      CCR (predicted by the numerical simulations) were found for the same rotation
      rate range, indicating that there is an optimal operational space with practical
      consequences on RCF performance. Experimental data of a large-scale perfusion run
      employing the simulated RCF showed high cell viabilities for over 100 days, which
      is probably related to the fact that the computed shear stress level in the
      system was shown to be relatively low (below 20 Pa under all tested conditions).

PMID- 25059209
TI  - Precise ex vivo histological validation of heightened cellularity and diffusion
      restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases
      of high-grade glioma.
AB  - BACKGROUND: Recent conflicting reports have found both brain tumor
      hypercellularity and necrosis in regions of restricted diffusion on MRI-derived
      apparent diffusion coefficient (ADC) images. This study precisely compares ADC
      and cell density voxel by voxel using postmortem human whole brain samples.
      METHODS: Patients with meningioma were evaluated to determine a normative ADC
      distribution within benign fluid attenuated inversion recovery (FLAIR)
      T2/hyperintensity surrounding tumor. This distribution was used to calculate a
      minimum ADC threshold to define regions of ADC-FLAIR mismatch (AFMM), where
      restricted diffusion presented in conjunction with T2/FLAIR hyperintensity.
      Contrast-enhancing voxels were excluded from this analysis. AFMM maps were
      generated using imaging acquired prior to death in 7 patients with high-grade
      glioma who eventually donated their brains upon death. Histological samples were
      taken from numerous regions of abnormal FLAIR and AFMM. Each sample was
      computationally processed to determine cell density. Custom software was then
      used to downsample coregistered microscopic histology to the more coarse MRI
      resolution. A voxel-by-voxel evaluation comparing ADC and cellularity was then
      performed. RESULTS: An ADC threshold of 0.929 * 10(-3) mm(2)/s was calculated
      from meningioma-induced edema and was used to define AFMM. Regions of AFMM showed
      significantly greater cell density in 6 of 7 high-grade glioma cases compared
      with regions of hyperintense FLAIR alone (P < .0001). Two patients had small
      regions of diffusion-restricted necrosis that had significantly lower ADC than
      nearby hypercellularity. CONCLUSIONS: Regions of AFMM contain hypercellularity
      except for regions with extremely restricted diffusion, where necrosis is
      present.

PMID- 25059210
TI  - Association between functional gastrointestinal diseases and exposure to abuse in
      teenagers.
AB  - Abdominal pain-predominant functional gastrointestinal diseases (AP-FGD) are
      common in children and commonly attributed to exposure to child abuse. However,
      this relationship has not been studied in teenagers, and the main objective of
      the current study was to assess it. Teenagers were recruited from four randomly
      selected schools in Western province of Sri Lanka. Data were collected using a
      validated self-administered questionnaire. AP-FGD were diagnosed using Rome III
      criteria. A total of 1850 teenagers aged 13-18 years were included. Three hundred
      and five (16.5%) had AP-FGD. AP-FGD were significantly higher in those exposed to
      sexual (34.0%), emotional (25.0%) and physical (20.2%) abuse, than in those not
      abused (13.0%, p < 0.001). Those with AP-FGD exposed to abuse had a higher
      severity score for bowel symptoms (30.8% vs. 24.7% in not abused, p < 0.05). This
      study highlights the importance of identifying exposure to abuse in management of
      teenagers with AP-FGD. 

PMID- 25059211
TI  - Simultaneous Concentration of Bovine Viruses and Agricultural Zoonotic Bacteria
      from Water Using Sodocalcic Glass Wool Filters.
AB  - Infiltration and runoff from manured agricultural fields can result in livestock
      pathogens reaching groundwater and surface waters. Here, we measured the
      effectiveness of glass wool filters to simultaneously concentrate enteric viruses
      and bacteria of bovine origin from water. The recovery efficiencies were
      determined for bovine viral diarrhea virus types 1 and 2, bovine rotavirus group
      A, bovine coronavirus, poliovirus Sabin III, toxigenic Escherichia coli ,and
      Campylobacter jejuni seeded into water with three different turbidity levels
      (0.5, 215, and 447 NTU). Twenty liters of dechlorinated tap water (pH 7) were
      seeded with the test organisms, and then passed through a glass wool filter using
      a peristaltic pump (flow rate = 1 liter min(-1)). Retained organisms were eluted
      from the filters by passing beef extract-glycine buffer (pH 9.5) in the direction
      opposite of sample flow. Recovered organisms were enumerated by qPCR except for
      C. jejuni, which was quantified by culture. Mean recovery efficiencies ranged
      from 55 to 33% for the bacteria and 58 to 16% for the viruses. Using
      bootstrapping techniques combined with Analysis of Variance, recovery
      efficiencies were found to differ among the pathogen types tested at the two
      lowest turbidity levels; however, for a given pathogen type turbidity did not
      affect recovery except for C. jejuni. Glass wool filtration is a cost-effective
      method for concentrating several waterborne pathogens of bovine origin
      simultaneously, although recovery may be low for some specific taxa such as
      bovine viral diarrhea virus 1.

PMID- 25059212
TI  - Norovirus GII.17 Predominates in Selected Surface Water Sources in Kenya.
AB  - In this study, the prevalence and genotypes of noroviruses (NoVs) in selected
      water sources from rural, urban and refugee settings in Kenya were investigated.
      Ten litres each of river, household and borehole water was collected in rural
      (Mboone River), urban (Nairobi and Mutoine River) and refugee (Dadaab refugee
      camp) settings. NoVs were recovered from the water samples by a glass wool
      adsorption-elution technique and/or PEG/NaCl precipitation. Nucleic acid was
      extracted using the automated MagNA Pure platform. NoVs were detected with
      singleplex real-time reverse transcription-polymerase chain reaction assays and
      characterised by nucleotide sequence analysis. NoVs were detected in 63% (25/40)
      of the selected water samples comprising GII (42.5%), GI (2.5%) and mixed GI/GII
      (17.5%) positive samples. The prevalence of NoVs in the Mutoine River (urban
      area) was higher than in the Mboone River (rural area) (P = 0.0013). Noroviruses
      GI.1, GI.3, GI.9, GII.4, GII.6, GII.12, GII.16 and GII.17 were identified, with
      GII.17 accounting for 76% (16/21) of the typed strains. The NoV GII.17
      predominance differs to other studies in Africa and further surveillance of NoVs
      in clinical and environmental settings is required to clarify/elucidate this
      observation. As information regarding NoVs in Kenyan water sources is limited
      this report provides valuable new data on NoV genotypes circulating in
      environmental water sources and the surrounding communities in Kenya.

PMID- 25059213
TI  - Estrogenic endocrine-disrupting chemicals modulate the production of inflammatory
      mediators and cell viability of lipopolysaccharide-stimulated macrophages.
AB  - Estrogenic endocrine-disrupting chemicals (EDCs) are exogenous substances that
      act as competitive inhibitors of estrogen in the endocrine system. By disrupting
      the endocrine system, EDCs can cause severe disabilities and diseases, including
      cancers and altered sexual development. Although the influence of these molecules
      in the endocrine system is evident, the effects of EDCs on the immune system as
      well as their cytotoxicity have been poorly examined. Therefore, we selected 21
      EDCs that are commonly found in Korean ecosystems, such as surface waters and
      effluents, and studied their immunologic effects by comparing nitric oxide (NO)
      production and cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7
      cells (RAW cells), a macrophage cell line. Among the EDCs tested, fenitrothion
      (FTH) inhibited the messenger RNA (mRNA) expression of inducible NO synthase
      (iNOS), resulting in reduced NO production, while treatment with andostenedione
      (AD), diethyl phthalate, di-n-butyl phthalate (DBP), estriol, or molinate
      decreased production of NO in an iNOS-independent fashion. In contrast,
      benzo(a)pyrene (B(a)P) increased the production of NO in RAW cells. In addition,
      AD, DBP, or FTH inhibited the mRNA expression of tumor necrosis factor alpha or
      interleukin-1 beta. Treatment with 17-alpha-ethynylestradiol, 17-beta-estradiol,
      4-n-butyl phenol, or alachlor induced apoptosis of RAW cells, while dicyclohexyl
      phthalate and B(a)P caused cell death in an apoptosis-independent manner. These
      data suggest that EDCs can influence the immune response to pathogens by
      modulating the functions of macrophages. 

PMID- 25059214
TI  - Effects of mouse hepcidin 1 treatment on osteoclast differentiation and
      intracellular iron concentration.
AB  - Hepcidin is a key player in the regulation of mammalian iron homeostasis. Because
      iron overload may be one of the causes of osteoporosis, hepcidin may have
      therapeutic potential for osteoporosis patients. However, the effects of hepcidin
      on bone metabolism are not fully clear. We recently found that hepcidin can
      increase intracellular iron and calcium levels and promote mineralization in
      osteoblasts. The present study was designed to evaluate the effects of hepcidin
      on osteoclasts. Our results showed that mouse hepcidin 1 (MH1) can increase the
      number of TRAP-positive MNCs concomitant in both bone marrow-derived macrophages
      (BMMs) and RAW264.7 cells and upregulate mRNA levels of TRAP, cathepsin K, and
      MMP-9 and increase TRAP-5b protein secretion in RAW264.7 cells. Moreover, MH1 can
      downregulate the level of FPN1 protein and increase intracellular iron in RAW
      264.7 cells. Therefore, we conclude that MH1 can significantly facilitate
      osteoclast differentiation in vitro. The mechanism behind accelerated
      differentiation may be associated with increased levels of intracellular iron.
      These findings may facilitate understanding of the effects of hepcidin on bone
      metabolism. 

PMID- 25059215
TI  - Systemic mastocytosis in a patient with Cowden syndrome.

PMID- 25059217
TI  - Isomeric chain structures of {[Mn(H2O)4]2Ru2(CO3)4Br2}n(n-): syntheses,
      structural diversity and magnetic properties.
AB  - The self-assembly of Ru2(CO3)4(3-) paddle-wheel precursors and Mn(2+) ions in
      aqueous solution yields various carbonate complexes. With appropriate selection
      of the synthetic conditions, we are able to intentionally tune the composition
      and structure of Mn-Ru2-carbonate assemblies to form infinite chain structural
      complexes, e.g., K[{Mn(H2O)4}2Ru2(CO3)4Br2].H2O (1) and
      H[{Mn(H2O)4}2Ru2(CO3)4Br2].6H2O (2). Complexes 1 and 2 are obtained at different
      temperatures (25  degrees C for 1 and 5  degrees C for 2, respectively), and
      their crystal structures consist of brick-wall stacked chains, in which
      neighboring Ru2(CO3)4Br2(5-) units are linked by two disubstituted octahedral
      Mn(H2O)4(2+) in a cis manner, resulting in two isomeric (twisted and zigzag)
      negative double-chain alpha- and beta-{[Mn(H2O)4]2Ru2(CO3)4Br2}n(n-). The
      magnetic properties of complexes 1 and 2 were highly characterized. The
      alternating current (AC) susceptibility analysis of complex 1 reveals a two-step
      magnetism transition at T1 = 5.0 K and T2 = 2.6 K, respectively. Complex 2
      exhibits metamagnetism behavior, with a transition field H(C) = ~1.2 kOe at 2.0
      K.

PMID- 25059219
TI  - Mechanism of TiO2 nanoparticle-induced neurotoxicity in zebrafish (Danio rerio).
AB  - Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of
      environmental and aqueous toxicants, and there is an emerging literature
      reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos.
      Few researches, however, are focused on the neurotoxicity on adult zebrafish
      after subchronic exposure to TiO2 NPs. This study was designed to evaluate the
      morphological changes, alterations of neurochemical contents, and expressions of
      memory behavior-related genes in zebrafish brains caused by exposures to 5, 10,
      20, and 40 MUg/L TiO2 NPs for 45 consecutive days. Our data indicated that
      spatial recognition memory and levels of norepinephrine, dopamine, and 5
      hydroxytryptamine were significantly decreased and NO levels were markedly
      elevated, and over proliferation of glial cells, neuron apoptosis, and TiO2 NP
      aggregation were observed after low dose exposures of TiO2 NPs. Furthermore, the
      low dose exposures of TiO2 NPs significantly activated expressions of C-fos, C
      jun, and BDNF genes, and suppressed expressions of p38, NGF, CREB, NR1, NR2ab,
      and GluR2 genes. These findings imply that low dose exposures of TiO2 NPs may
      result in the brain damages in zebrafish, provide a developmental basis for
      evaluating the neurotoxicity of subchronic exposure, and raise the caution of
      aquatic application of TiO2 NPs.

PMID- 25059218
TI  - Differential hippocampal gene expression and pathway analysis in an etiology
      based mouse model of major depressive disorder.
AB  - We have recently reported the creation and initial characterization of an
      etiology-based recombinant mouse model of a severe and inherited form of Major
      Depressive Disorder (MDD). This was achieved by replacing the corresponding mouse
      DNA sequence with a 6-base DNA sequence from the human CREB1 promoter that is
      associated with MDD in individuals from families with recurrent, early-onset MDD
      (RE-MDD). In the current study, we explored the effect of the pathogenic Creb1
      allele on gene expression in the mouse hippocampus, a brain region that is
      altered in structure and function in MDD. Mouse whole-genome profiling was
      performed using the Illumina MouseWG-6 v2.0 Expression BeadChip microarray.
      Univariate analysis identified 269 differentially-expressed genes in the
      hippocampus of the mutant mouse. Pathway analyses highlighted 11 KEGG pathways:
      the phosphatidylinositol signaling system, which has been widely implicated in
      MDD, Bipolar Disorder, and the action of mood stabilizers; gap junction and long
      term potentiation, which mediate cognition and memory functions often impaired in
      MDD; cardiac muscle contraction, insulin signaling pathway, and three
      neurodegenerative brain disorders (Alzheimer's, Parkinson's, and Huntington's
      Diseases) that are associated with MDD; ribosome and proteasome pathways
      affecting protein synthesis/degradation; and the oxidative phosphorylation
      pathway that is key to energy production. These findings illustrate the merit of
      this congenic C57BL/6 recombinant mouse as a model of RE-MDD, and demonstrate its
      potential for highlighting molecular and cellular pathways that contribute to the
      biology of MDD. The results also inform our understanding of the mechanisms that
      underlie the comorbidity of MDD with other disorders.

PMID- 25059220
TI  - Boehringer Ingelheim withheld safety analyses on new anticoagulant, The BMJ
      investigation finds.

PMID- 25059221
TI  - High-performance information search filters for CKD content in PubMed, Ovid
      MEDLINE, and EMBASE.
AB  - BACKGROUND: Finding relevant articles in large bibliographic databases such as
      PubMed, Ovid MEDLINE, and EMBASE to inform care and future research is
      challenging. Articles relevant to chronic kidney disease (CKD) are particularly
      difficult to find because they are often published under different terminology
      and are found across a wide range of journal types. STUDY DESIGN: We used
      computer automation within a diagnostic test assessment framework to develop and
      validate information search filters to identify CKD articles in large
      bibliographic databases. SETTING & PARTICIPANTS: 22,992 full-text articles in
      PubMed, Ovid MEDLINE, or EMBASE. INDEX TEST: 1,374,148 unique search filters.
      REFERENCE TEST: We established the reference standard of article relevance to CKD
      by manual review of all full-text articles using prespecified criteria to
      determine whether each article contained CKD content or not. We then assessed
      filter performance by calculating sensitivity, specificity, and positive
      predictive value for the retrieval of CKD articles. Filters with high sensitivity
      and specificity for the identification of CKD articles in the development phase
      (two-thirds of the sample) were then retested in the validation phase (remaining
      one-third of the sample). RESULTS: We developed and validated high-performance
      CKD search filters for each bibliographic database. Filters optimized for
      sensitivity reached at least 99% sensitivity, and filters optimized for
      specificity reached at least 97% specificity. The filters were complex; for
      example, one PubMed filter included more than 89 terms used in combination,
      including "chronic kidney disease," "renal insufficiency," and "renal fibrosis."
      In proof-of-concept searches, physicians found more articles relevant to the
      topic of CKD with the use of these filters. LIMITATIONS: As knowledge of the
      pathogenesis of CKD grows and definitions change, these filters will need to be
      updated to incorporate new terminology used to index relevant articles.
      CONCLUSIONS: PubMed, Ovid MEDLINE, and EMBASE can be filtered reliably for
      articles relevant to CKD. These high-performance information filters are now
      available online and can be used to better identify CKD content in large
      bibliographic databases.

PMID- 25059223
TI  - Potential application of notochordal cells for intervertebral disc regeneration:
      an in vitro assessment.
AB  - Recent studies suggest that notochordal cells (NCs) might be involved in
      intervertebral disc homeostasis, a role exploitable to counteract matrix
      degradation as observed during degeneration. This study aimed to evaluate the
      potential of NCs to promote matrix production by nucleus pulposus cells (NPCs)
      and to compare it to the currently proposed addition of bone marrow stromal cells
      (BMSCs). Using alginate beads, bovine NPCs were exposed for 28 d to porcine NC
      conditioned medium (NCCM); direct co-culture with porcine NCs or bovine BMSCs; or
      the combination of BMSCs and NCCM. Effects on cell proliferation, disc matrix
      production (proteoglycans, collagens) and disc matrix protein expression
      (aggrecan, collagen 1 and 2, SOX9) were determined and compared to TGFbeta
      stimulation. NCCM strongly promoted NPC proliferation (x 2.2) and matrix
      production (x 3.9) to levels similar to that with TGFbeta, whereas the direct
      addition of NCs had no effect. Co-culture of NPCs and BMSCs led to proteoglycan
      synthesis similar to NPCs alone, which was slightly improved by NCCM (x 1.5).
      Histological analysis confirmed biochemical data. Gene expression of analysed
      proteins remained stable for all groups and unaffected by medium conditions. NCs
      could substantially stimulate NPCs through factors secreted into conditioned
      medium and in levels similar to the addition of BMSCs. This study showed that
      molecular agents secreted by NCs constitute a promising alternative to the
      proposed "standard" injection of BMSCs for disc repair: their effects are
      similar, do not require the injection of a large number of cells and can be
      further amplified when the factors are identified.

PMID- 25059222
TI  - Serum albumin and kidney function decline in HIV-infected women.
AB  - BACKGROUND: Serum albumin concentrations are a strong predictor of mortality and
      cardiovascular disease in human immunodeficiency virus (HIV)-infected
      individuals. We studied the longitudinal associations between serum albumin
      levels and kidney function decline in a population of HIV-infected women. STUDY
      DESIGN: Retrospective cohort analysis. SETTING & PARTICIPANTS: Study participants
      were recruited from the Women's Interagency HIV Study (WIHS), a large
      observational study designed to understand risk factors for the progression of
      HIV infection in women living in urban communities. 908 participants had baseline
      assessment of kidney function and 2 follow-up measurements over an average of 8
      years. PREDICTOR: The primary predictor was serum albumin concentration.
      OUTCOMES: We examined annual change in kidney function. Secondary outcomes
      included rapid kidney function decline and incident reduced estimated glomerular
      filtration rate (eGFR). MEASUREMENTS: Kidney function decline was determined by
      cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and
      follow-up. Each model was adjusted for kidney disease and HIV-related risk
      factors using linear and relative risk regression. RESULTS: After multivariate
      adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was
      associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001),
      which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for
      albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In
      adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was
      associated with a 1.71-fold greater risk of rapid kidney function decline (P <
      0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001).
      LIMITATIONS: The cohort is composed of only female participants from urban
      communities within the United States. CONCLUSIONS: Lower serum albumin levels
      were associated strongly with kidney function decline and incident reduced eGFRs
      in HIV-infected women independent of HIV disease status, body mass index, and
      albuminuria.

PMID- 25059224
TI  - Electronic health records and resident workflow: a time-motion study of
      otolaryngology residents.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the impact of electronic health records (EHRs)
      on the workflow of otolaryngology residents. STUDY DESIGN: Prospective, time
      motion study. METHODS: A time-motion study was conducted both in the 2009 to 2010
      and 2012 to 2013 postgraduate years. Eight otolaryngology residents were directly
      observed on both operative and clinic days, with resident activities categorized
      by way of a database program. Comparisons were made to the same data collected in
      the same setting prior to and following integration of an EHR system. RESULTS:
      Residents spent their day on direct patient care (41.1%), indirect patient care
      (35.3%), didactic education (14.0%), personal activities (6.9%), and transit
      (3.1%). The primary activity during operative days was direct patient care, and
      during clinic days it was indirect patient care. Activities of marginal
      educational value comprised a considerable component of their time (16.5%).
      Compared to data collected prior to use of an EHR, time was spent similarly.
      However, residents using an EHR devoted significantly more time to indirect
      patient care on clinic days (P < .05). CONCLUSIONS: This is the first study to
      evaluate EHR integration on otolaryngology resident workflow. Overall resident
      efficiency was not significantly altered by the implementation of an EHR.
      However, more time was shifted from directly caring for patients to documenting
      on the EHR in the clinic setting. These findings provide an important objective
      insight into EHRs, especially given the looming mandate for their use and the
      need to streamline resident curriculum in the duty hours era.

PMID- 25059225
TI  - Levels of adiponectin and leptin at onset of type 1 diabetes have changed over
      time in children and adolescents.
AB  - Adiponectin and leptin are proteins secreted by the adipose tissue and have an
      influence on insulin sensitivity and on inflammatory markers. Altered levels
      could play a part in the pathogenesis of type 1 diabetes mellitus. We determined
      adiponectin and leptin levels over a nine-year period in children with type 1
      diabetes mellitus (T1D) in relation to the increasing incidence of T1D, and
      studied the impact of patient status, age, gender and body mass index (BMI). Data
      were derived from a population-based registry of diabetic children (DanDiabKids)
      from 1997 to 2005. Children with newly diagnosed T1D (n = 482) were included, and
      healthy siblings (n = 479) were chosen as a control group. Leptin levels were
      significantly higher in recent years (in both patients and siblings), whereas for
      adiponectin, the levels were lower in recent years in the patient group. Leptin
      levels were lower in children with T1D (RR 0.74, p = 0.003) and in males (RR
      0.52, p < 0.001) and increasing with age in both groups. For adiponectin, there
      was a negative association between level and age in patients. Both adipokines
      showed a significant correlation with BMI and lower levels in children with blood
      samples taken within the first 2 days after initiation of insulin treatment.
      There has been a change in leptin and adiponectin levels in children with or
      without T1D from 1997 to 2005. This is not explained by changes in BMI and may
      reflect changes in other factors like diet or physical activity.

PMID- 25059226
TI  - Melatonin synergized with cyclosporine A improves cardiac allograft survival by
      suppressing inflammation and apoptosis.
AB  - Melatonin, a widespread physiological mediator, has been demonstrated to exhibit
      a dose-dependent immunoregulatory effect in vitro and in vivo, including
      mediating physiological circadian rhythms, neutralizing free radicals and
      exerting antisenescence actions. In the present study, the efficacy and mechanism
      of melatonin alone or in combination with cyclosporine (CsA) in prolonging heart
      transplantation survival was examined. Daily treatment with melatonin (200
      mg/kg/day) through a gavage, significantly prolonged the survival of cardiac
      grafts (mean survival time, 13.4+/-2.4 days; n=7; P<0.0001) compared with the
      untreated controls (5.8+/-1.2 days; n=7). When CsA (5 mg/kg/day) was co
      administered with melatonin (50 mg/kg/day), the survival rate improved (31.6+/
      2.4 days; n=7; P<0.001), compared with that achieved by only 20 mg/kg/day CsA
      (22+/-2.8 days; n=7). As expected, melatonin significantly alleviated the
      inflammatory response and apoptosis as determined by TdT-mediated dUTP-biotin
      nick end labeling assay (P<0.05). Further analysis demonstrated that melatonin
      significantly reduced p65 activation and the release of inflammatory factors.
      Therefore, these findings indicate that melatonin in combination with CsA
      protected the cardiac allograft by inhibiting inflammation-induced apoptosis.
      These results provide evidence for a novel therapeutic approach for future
      immunosuppressive agents in organ transplantation.

PMID- 25059227
TI  - Serum galectin-3 levels were associated with proteinuria in patients with
      Familial Mediterranean Fever.
AB  - BACKGROUND: The most common and pernicious complication of Familial Mediterranean
      fever (FMF) is renal amyloidosis, usually affecting the kidneys, leading to end
      stage renal failure. FMF-related renal amyloidosis needed to be diagnosed early.
      Optimal colchicine dose is effective in preventing and reversing renal
      amyloidosis. Galectin-3, profibrotic mediator, has regulatory functions in
      inflammation, fibrosis and tumorigenesis. Galectin-3 is a strong prognostic
      marker for heart failure. Galectin-3 plays role in diabetic nephropathy and
      chronic kidney disease. The aim of the study is to investigate whether galectin-3
      is related to proteinuria and amyloidosis in FMF. METHODS: Seventy-five FMF
      patients who have no exclusion criteria and healthy controls (n = 36) were
      included. Serum galectin-3 was measured and morning spot urine was collected for
      determination of the protein/creatinine ratio (PCR). RESULTS: Serum Galectin-3
      levels were significantly higher in FMF patients than the control group [969.66
      (3825) pg/mL vs. 238 (921) pg/mL, respectively; P<0.001]. We classified into two
      groups: Group1 (n = 48) had FMF patients with proteniuria, Group2 (n = 27) had
      FMF patients without proteinuria. Group1 had higher levels of galectin-3 than
      Group2 [1106(3812) pg/mL vs. 867.3(1433) pg/mL, P < 0.001]. Galectin-3 levels
      were correlated with PCR in whole group and FMF group (r = 0.785, P < 0.001 and r
      = 0.803, P < 0.001). In ROC curve, best cutoff value = 581.50 pg/mL was used to
      detect proteinuria (sensitivity = 91.7 %, specificity = 71.4 %, AUC = 0.879) and
      optimal cutoff value = 1458.00 pg/mL was an indicator of nephrotic-range
      proteinuric (sensitivity = 100 %, specificity = 92.1 %, AUC = 0.983). CONCLUSION:
      Galectin-3 is associated with proteinuria and renal amyloidosis in FMF. Galectin
      3 may play role in pathogenesis of amyloidosis.

PMID- 25059228
TI  - Comparison of predictive value for first cardiovascular event between Japanese
      GFR equation and coefficient-modified CKD-EPI equation.
AB  - BACKGROUND: The most superior GFR-estimating equation from the viewpoint of
      cardiovascular disease (CVD) prediction remains unclear. Thus, we performed cross
      sectional comparison between two GFR-estimating equations (Japanese GFR equation
      and coefficient-modified CKD-EPI equation) and CVD incidence using Japanese
      nationwide "specific health checkup" data. METHODS: We recruited Japanese
      residents (241,159 individuals; mean 63 years; male, 38.6 %) who had not
      experienced CVD event (cardiac disease or stroke, or both). We calculated
      estimated GFR using two equations, and compared their predictive value for first
      symptomatic CVD event within 1 year. RESULTS: Of all subjects, the mean GFR
      estimated by the Japanese GFR equation (JPN-eGFR) modified for Japanese was 75.83
      +/- 16.18 mL/min/1.73 m(2), and that by the coefficient-modified CKD-EPI equation
      (mCKDEPI-eGFR) was 76.39 +/- 9.61 mL/min/1.73 m(2). Area under the receiver
      operating characteristics curves (95 % confidence intervals) for predicting CVD
      event by mCKDEPI-eGFR vs. JPN-eGFR were 0.596 (0.589-0.603) vs. 0.562 (0.554
      0.569). Using mCKDEPI-eGFR, the crude odds ratio (OR) for CVD incident in the 4th
      quartile group was far more than double (OR 2.46, 95 % CI 2.29-2.66) that in the
      1st quartile group. Using JPN-eGFR, the crude OR in the 4th quartile group was
      less than double (OR 1.61, 95 % CI 1.51-1.73) that in the 1st quartile group.
      However, such superior predictive value of mCKDEPI-eGFR disappeared after
      adjustment for confounding factors (age, gender, BMI, presence of proteinuria,
      hypertension, diabetes, dyslipidemia and current smoking). CONCLUSION: GFR
      estimated by the coefficient-modified CKD-EPI equation was more closely related
      to CVD incidence than that estimated by the Japanese GFR equation. However, it is
      possible that low mCKDEPI-eGFR also reflects some cardiovascular risk(s) other
      than kidney dysfunction.

PMID- 25059229
TI  - CD137-inducing factors from T cells and macrophages accelerate the
      destabilization of atherosclerotic plaques in hyperlipidemic mice.
AB  - CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily, has
      been reported to be expressed in atherosclerotic plaques, and to promote lesion
      formation. However, the role of CD137 in mediating atherosclerotic plaque
      stability and the possible underlying molecular and cellular mechanisms are
      poorly understood. Here, apolipoprotein E-deficient (ApoE(-/-)) and CD137
      deficient ApoE(-/-) (ApoE(-/-)CD137(-/-)) mice fed a chow diet for 66 wk were
      used. CD137 induces plaque instability, which is characterized by increased
      plaque necrosis, decreased collagen content, decreased vascular smooth muscle
      cell (VSMC) content, and increased macrophage infiltration. CD137 also increases
      the infiltration of effector T (Teff) cells into plaque lesion sites, resulting
      in increased interferon-gamma (IFN-gamma) expression. Interestingly, Teff-cell
      derived IFN-gamma inhibits collagen synthesis in atherosclerotic plaques.
      Furthermore, CD137 activation increases the apoptosis of VSMCs, possibly by
      decreasing the antiapoptotic regulator, Bcl-2, and subsequently up-regulating
      cleaved caspase-3. In macrophages, activation of CD137 signaling boosted the
      oxidized low density lipoprotein-induced expression of matrix metalloproteinase 9
      via the p38 mitogen-activated protein kinase and extracellular signal-regulated
      kinase1/2 signaling pathways. In summary, activation of CD137 signaling decreases
      the stability of advanced atherosclerotic plaques via its combined effects on
      Teff cells, VSMCs, and macrophages.

PMID- 25059230
TI  - Eicosanomic profiling reveals dominance of the epoxygenase pathway in human
      amniotic fluid at term in spontaneous labor.
AB  - Lipid mediators play an important role in reproductive biology, especially, in
      parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2
      (PGE2) and PGF2alpha, precedes the onset of labor as a result of increased
      expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism
      of arachidonic acid results in bioactive lipid mediators beyond prostaglandins
      that could significantly influence myometrial activity. Therefore, an unbiased
      lipidomic approach was used to profile the arachidonic acid metabolome of
      amniotic fluid. In this study, liquid chromatography-mass spectrometry was used
      for the first time to quantitate these metabolites in human amniotic fluid by
      comparing patients at midtrimester, at term but not in labor, and at term and in
      spontaneous labor. In addition to exposing novel aspects of COX pathway
      metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and
      lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable
      product selectivity. Despite their recognition as anti-inflammatory lipid
      mediators and regulators of ion channels, little is known about the epoxygenase
      pathway in labor. Epoxygenase pathway metabolites are established regulators of
      vascular homeostasis in cardiovascular and renal physiology. Their presence as
      the dominant lipid mediators in spontaneous labor at term portends a yet
      undiscovered physiological function in parturition.

PMID- 25059232
TI  - Puerarin facilitates T-tubule development of murine embryonic stem cell-derived
      cardiomyocytes.
AB  - AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CM) is one of the
      promising cell sources for repopulation of damaged myocardium. However, ES-CMs
      present immature structure, which impairs their integration with host tissue and
      functional regeneration. This study used murine ES-CMs as an in vitro model of
      cardiomyogenesis to elucidate the effect of puerarin, the main compound found in
      the traditional Chinese medicine the herb Radix puerariae, on t-tubule
      development of murine ES-CMs. METHODS: Electron microscope was employed to
      examine the ultrastructure. The investigation of transverse-tubules (t-tubules)
      was performed by Di-8-ANEPPS staining. Quantitative real-time PCR was utilized to
      study the transcript level of genes related to t-tubule development. RESULTS: We
      found that long-term application of puerarin throughout cardiac differentiation
      improved myofibril array and sarcomeres formation, and significantly facilitated
      t-tubules development of ES-CMs. The transcript levels of caveolin-3, amphiphysin
      2 and junctophinlin-2, which are crucial for the formation and development of t
      tubules, were significantly upregulated by puerarin treatment. Furthermore,
      puerarin repressed the expression of miR-22, which targets to caveolin-3.
      CONCLUSION: Our data showed that puerarin facilitates t-tubule development of
      murine ES-CMs. This might be related to the repression of miR-22 by puerarin and
      upregulation of Cav3, Bin1 and JP2 transcripts.

PMID- 25059231
TI  - Genetic drivers of metastatic dissemination in sonic hedgehog medulloblastoma.
AB  - Leptomeningeal dissemination (LMD), the metastatic spread of tumor cells via the
      cerebrospinal fluid to the brain and spinal cord, is an ominous prognostic sign
      for patients with the pediatric brain tumor medulloblastoma. The need to reduce
      the risk of LMD has driven the development of aggressive treatment regimens,
      which cause disabling neurotoxic side effects in long-term survivors. Transposon
      mediated mutagenesis studies in mice have revealed numerous candidate metastasis
      genes. Understanding how these genes drive LMD will require functional assessment
      using in vivo and cell culture models of medulloblastoma. We analyzed two genes
      that were sites of frequent transposon insertion and highly expressed in human
      medulloblastomas: Arnt (aryl hydrocarbon receptor nuclear translocator) and Gdi2
      (GDP dissociation inhibitor 2). Here we show that ectopic expression of Arnt and
      Gdi2 promoted LMD in mice bearing Sonic hedgehog (Shh)-induced medulloblastomas.
      We overexpressed Arnt and Gdi2 in a human medulloblastoma cell line (DAOY) and an
      immortalized, nontransformed cell line derived from mouse granule neuron
      precursors (SHH-NPD) and quantified migration, invasiveness, and anchorage
      independent growth, cell traits that are associated with metastatic competence in
      carcinomas. In SHH-NPD cells. Arnt and Gdi2 stimulated all three traits. In DAOY
      cells, Arnt had the same effects, but Gdi2 stimulated invasiveness only. These
      results support a mechanism whereby Arnt and Gdi2 cause cells to detach from the
      primary tumor mass by increasing cell motility and invasiveness. By conferring to
      tumor cells the ability to proliferate without surface attachment, Arnt and Gdi2
      favor the formation of stable colonies of cells capable of seeding the
      leptomeninges. 

PMID- 25059233
TI  - Which activity monitor to use? Validity, reproducibility and user friendliness of
      three activity monitors.
AB  - BACKGROUND: Health is associated with amount of daily physical activity.
      Recently, the identification of sedentary time as an independent factor, has
      gained interest. A valid and easy to use activity monitor is needed to
      objectively investigate the relationship between physical activity, sedentary
      time and health. We compared validity and reproducibility of physical activity
      measurement and posture identification of three activity monitors, as well as
      user friendliness. METHODS: Healthy volunteers wore three activity monitors
      simultaneously: ActivPAL3, ActiGraphGT3X and CAM. Data were acquired under both
      controlled (n = 5) and free-living conditions (n = 9). The controlled laboratory
      measurement, that included standardized walking intensity and posture allocation,
      was performed twice. User friendliness was evaluated with a questionnaire.
      Posture classification was compared with direct observation (controlled
      measurement) and with diaries (free living). Accelerometer intensity accuracy was
      tested by correlations with walking speed. User friendliness was compared between
      activity monitors. RESULTS: Reproducibility was at least substantial in all
      monitors. The difference between the two CAM measurements increased with walking
      intensity. Amount of correct posture classification by ActivPAL3 was 100.0%
      (kappa 0.98), 33.9% by ActiGraphGT3X (kappa 0.29) and 100.0% by CAM (kappa 0.99).
      Correlations between accelerometer intensity and walking speed were 0.98 for
      ActivPAL3, 1.00 for ActiGraphGT3X and 0.98 for CAM. ICCs between activity
      monitors and diary were 0.98 in ActivPAL3, 0.59 and 0.96 in ActiGraphGT3X and
      0.98 in CAM. ActivPAL3 and ActiGraphGT3X had higher user friendliness scores than
      the CAM. CONCLUSIONS: The ActivPAL3 is valid, reproducible and user friendly. The
      posture classification by the ActiGraphGT3X is not valid, but reflection of
      walking intensity and user friendliness are good. The CAM is valid; however,
      reproducibility at higher walking intensity and user friendliness might cause
      problems. Further validity studies in free living are recommended.

PMID- 25059234
TI  - Predictive value of systemic and local inflammation parameters in talc
      pleurodesis assessment.
AB  - BACKGROUND: One option for the palliative treatment of recurrent malignant
      pleural effusion is powdered talc using thoracoscopy. This paper presents the
      results of selected systemic and local manifestations of the talc-induced
      inflammatory reaction using a videothoracoscope. METHOD: A total of 114 patients
      with repeated malignant pleural effusion were treated at the Cardiac Surgery
      Clinic in Hradec Kralove from January 2010 to December 2012. Those with a life
      expectancy more than >= 3 months were eligible for talcage surgery. The group was
      retrospectively divided according to treatment results into Group A (N1 = 98 -
      successful) and Group B (N2 = 16 - relapsing). The pleural effusion was
      quantified using ultrasound over 1 year at 3-month intervals. Systemic changes
      due to the inflammatory reaction (body temperature, serum leukocyte and CRP
      levels) were evaluated. Local indicators of inflammation included changes in the
      leukocyte cell population in the effusion and changes in the pleural CRP levels.
      The dynamics of local expression of membrane receptors TLR-2 and CD-64 on
      granulocyte and monocyte cell populations in the pleural effusion were also
      evaluated. RESULTS: The reaction after talcage, included a significant increase
      in axillary temperature and leukocyte count, 12 h after the procedure. The
      dynamics were different in the two groups. The dynamics of local inflammatory
      changes were an early increase in the pleural CRP levels in both groups. The time
      interval of local inflammatory development and duration was related to the
      treatment efficacy and showed a significant rise 2 h after talcage in Group A. In
      Group B the local inflammatory reaction was slower and the rise was only observed
      24 h after talc application. A decrease in lymphocyte count and an increase in
      granulocyte count 2 h after talcage were found. After an initial drop in monocyte
      level, a rise occurred within 24 h after talcage. Changes in the expression of
      TLR-2 and CD-64 receptors in relation to their cell carriers were observed
      depending on time after talcage. CONCLUSION: The differences in the serum and
      pleural effusion CRP levels suggest that the surgical stress manifests itself
      locally in the pleural space with a lower intensity and time delay. The TLR-2 and
      CD-64 receptors exhibit different behaviour depending on the type of cell
      membrane where they are found. The inverse relation between the granulocyte
      increase and TLR-2 receptor decrease in the membrane immediately after talcage is
      a new finding. The dynamics of TLR-2 expression on the monocytes demonstrates a
      direct proportion between the increasing expression of the TLR-2 receptor and
      increasing percent fraction of the cell carrier.

PMID- 25059235
TI  - Preparing compound heterozygous reference material using gene synthesis
      technology: a model of thrombophilic mutations.
AB  - AIMS: The aim of our study is to present a novel approach for preparing a
      compound heterozygous reference material (hetRM) using gene synthesis technology
      with inverted insertion of wild-type and mutant fragments into a single cloning
      vector. Factor II (G20210A) and Factor V (G1691A Leiden) gene mutations were used
      as an experimental model. METHODS: During the gene synthesis, DNA fragments were
      aligned in the following order: G1691 FV wild-type forward strain, G20210 FII
      wild-type forward strain, 1691A FV mutant reverse strain, 20210A FII mutant
      reverse strain. The complete chain was inserted into a pIDT SMART cloning vector
      and amplified in an E. coli competent strain. For assessing hetRM characteristics
      and commutability, we used real-time PCR with subsequent melting curve analysis,
      real-time PCR with hydrolysis probes, allele-specific amplification, reverse
      hybridization, and dideoxynucleotide DNA sequencing. RESULT: All five methods
      yielded concordant results of DNA analysis of the hetRM. Differences in real-time
      PCR cycle threshold values after six-months of storage at -80  degrees C were not
      statistically significant from those obtained from freshly prepared hetRM
      aliquots, which is a good indication of their stability. CONCLUSION: By applying
      the procedures of gene synthesis and cloning technology, we prepared and verified
      a model genetic reference material for FII G20210A and FV G1691A testing with a
      compound heterozygous genotype. The hetRM was stable, commutable, and available
      in large quantities and in a wide concentration range.

PMID- 25059236
TI  - Murine pressure overload models: a 30-MHz look brings a whole new "sound" into
      data interpretation.
AB  - Transverse aortic constriction (TAC) and angiotensin II (ANG II) subcutaneous
      osmotic pump infusion are frequently used murine models of pressure overload
      hypertrophy. The aim of this paper is to investigate time- and stressor-dependent
      functional and structural changes using echocardiographic B-mode, M-mode, and
      Doppler characterization. Ten-week-old male C57BL6/J wild-type mice received 4-wk
      ANG II (1.5 mg.kg(-1).day(-1), n = 19) or saline (n = 10) infusion followed by
      echocardiography (Vevo2100, Visual Sonics), or underwent TAC (n = 63) or a sham
      operation (n = 30). In the TAC protocol, echocardiography was performed after 2
      wk (n = 22 TAC, n = 10 sham), after 4 wk (n = 20 TAC, n = 10 sham), and after 10
      wk (n = 21 TAC, n = 10 sham). ANG II infusion was associated with a mixed
      pressure and volume overload, with a variable contribution of volume overload
      caused by aortic valve insufficiency (grade 0.5-3.5/4). The degree of aortic
      valve insufficiency correlated with the degree of left ventricular dilation (r(2)
      = 0.671, P < 0.001). After TAC, all hypertrophic remodeling patterns known in
      human disease were observed: 1) low-flow, low-gradient with preserved ejection
      fraction (EF); 2) concentric hypertrophy with normal EF and flow; 3) concentric
      hypertrophy with moderately decreased EF and/or flow; 4) eccentric hypertrophy
      with normal EF and flow; 5) eccentric hypertrophy with moderately decreased EF
      and/or flow; and 6) eccentric hypertrophy with severely depressed EF. Eccentric
      remodeling was time dependent, with 5% of mice developing this phenotype at 2 wk,
      39% at 4 wk, and 59% at 10 wk. Comprehensive echocardiographic analysis allows
      identification of homogeneous subgroups of mice subjected to hypertrophic stress,
      reducing variability in experimental results and facilitating clinical
      translation. 

PMID- 25059237
TI  - Heat stress protects against mechanical ventilation-induced diaphragmatic
      atrophy.
AB  - Mechanical ventilation (MV) is a life-saving intervention in patients who are
      incapable of maintaining adequate pulmonary gas exchange due to respiratory
      failure or other disorders. However, prolonged MV is associated with the
      development of respiratory muscle weakness. We hypothesized that a single
      exposure to whole body heat stress would increase diaphragm expression of heat
      shock protein 72 (HSP72) and that this treatment would protect against MV-induced
      diaphragmatic atrophy. Adult male Wistar rats (n = 38) were randomly assigned to
      one of four groups: an acutely anesthetized control group (CON) with no MV; 12-h
      controlled MV group (CMV); 1-h whole body heat stress (HS); or 1-h whole body
      heat stress 24 h prior to 12-h controlled MV (HSMV). Compared with CON animals,
      diaphragmatic HSP72 expression increased significantly in the HS and HSMV groups
      (P < 0.05). Prolonged MV resulted in significant atrophy of type I, type IIa, and
      type IIx fibers in the costal diaphragm (P < 0.05). Whole body heat stress
      attenuated this effect. In contrast, heat stress did not protect against MV
      induced diaphragm contractile dysfunction. The mechanisms responsible for this
      heat stress-induced protection remain unclear but may be linked to increased
      expression of HSP72 in the diaphragm. 

PMID- 25059238
TI  - Cardiac function is preserved following 4 weeks of voluntary wheel running in a
      rodent model of chronic kidney disease.
AB  - The purpose of this investigation was to determine the effect of 4 wk of
      voluntary wheel running on cardiac performance in the 5/6 ablation-infarction
      (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary
      wheel running would be effective in preserving cardiac function in AI. Male
      Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary
      nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI.
      Animals were maintained over a total period of 8 wk following AI and sham
      surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk
      voluntary wheel-running intervention/sedentary control period. Cardiac
      performance was assessed using an isolated working heart preparation. Left
      ventricular (LV) tissue was used for biochemical tissue analysis. In addition,
      soleus muscle citrate synthase activity was measured. AI-WR rats performed a low
      volume of exercise, running an average of 13 +/- 2 km, which resulted in citrate
      synthase activity not different from that in sham animals. Isolated AI-SED hearts
      demonstrated impaired cardiac performance at baseline and in response to
      preload/afterload manipulations. Conversely, cardiac function was preserved in AI
      WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO)
      synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In
      addition, LV H2O2 in AI-WR was similar to that of sham and associated with
      increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2.
      The findings of the current study suggest that a low-volume exercise intervention
      is sufficient to maintain cardiac performance in rats with CKD, potentially
      through a mechanism related to improved redox homeostasis and increased NO. 

PMID- 25059239
TI  - Structural remodeling of coronary resistance arteries: effects of age and
      exercise training.
AB  - Age is known to induce remodeling and stiffening of large-conduit arteries;
      however, little is known of the effects of age on remodeling and mechanical
      properties of coronary resistance arteries. We employed a rat model of aging to
      investigate whether 1) age increases wall thickness and stiffness of coronary
      resistance arteries, and 2) exercise training reverses putative age-induced
      increases in wall thickness and stiffness of coronary resistance arteries. Young
      (4 mo) and old (21 mo) Fischer 344 rats remained sedentary or underwent 10 wk of
      treadmill exercise training. Coronary resistance arteries were isolated for
      determination of wall-to-lumen ratio, effective elastic modulus, and active and
      passive responses to changes in intraluminal pressure. Elastin and collagen
      content of the vascular wall were assessed histologically. Wall-to-lumen ratio
      increased with age, but this increase was reversed by exercise training. In
      contrast, age reduced stiffness, and exercise training increased stiffness in
      coronary resistance arteries from old rats. Myogenic responsiveness was reduced
      with age and restored by exercise training. Collagen-to-elastin ratio (C/E) of
      the wall did not change with age and was reduced with exercise training in
      arteries from old rats. Thus age induces hypertrophic remodeling of the vessel
      wall and reduces the stiffness and myogenic function of coronary resistance
      arteries. Exercise training reduces wall-to-lumen ratio, increases wall
      stiffness, and restores myogenic function in aged coronary resistance arteries.
      The restorative effect of exercise training on myogenic function of coronary
      resistance arteries may be due to both changes in vascular smooth muscle
      phenotype and expression of extracellular matrix proteins. 

PMID- 25059240
TI  - Acute volume loading and exercise capacity in postural tachycardia syndrome.
AB  - Postural tachycardia syndrome (POTS) is associated with exercise intolerance,
      hypovolemia, and cardiac atrophy, which may contribute to reduced stroke volume
      and compensatory exaggerated heart rate (HR) increases. Acute volume loading with
      intravenous (iv) saline reduces HR and improves orthostatic tolerance and
      symptoms in POTS, but its effect on exercise capacity is unknown. In this study,
      we determined the effect of iv saline infusion on peak exercise capacity
      (VO2peak) in POTS. Nineteen patients with POTS participated in a sequential
      study. VO2peak was measured on two separate study days, following administration
      of placebo or 1 liter of i.v. saline (NaCl 0.9%). Patients exercised on a
      semirecumbent bicycle with resistance increased by 25 W every 2 min until maximal
      effort was achieved. Patients exhibited blood volume deficits (-13.4 +/- 1.4%
      ideal volume), consistent with mild to moderate hypovolemia. At baseline, saline
      significantly increased stroke volume (saline 80 +/- 8 ml vs. placebo 64 +/- 4
      ml; P = 0.010), increased cardiac output (saline 6.9 +/- 0.5 liter/min vs.
      placebo 5.7 +/- 0.2 liter/min; P = 0.021), and reduced systemic vascular
      resistance (saline 992.6 +/- 70.0 dyn-s/cm(5) vs. placebo 1,184.0 +/- 50.8 dyn
      s/cm(5); P = 0.011), with no effect on HR or blood pressure. During exercise,
      saline did not produce differences in VO2peak (saline 26.3 +/- 1.2 mg.kg(-1).min(
      1) vs. placebo 27.7 +/- 1.8 mg.kg(-1).min(-1); P = 0.615), peak HR [saline 174 +/
      4 beats per minute (bpm) vs. placebo 175 +/- 3 bpm; P = 0.672] or other
      cardiovascular parameters. These findings suggest that acute volume loading with
      saline does not improve VO2peak or cardiovascular responses to exercise in POTS,
      despite improvements in resting hemodynamic function.

PMID- 25059241
TI  - Effects of water stratification and mixing on microbial community structure in a
      subtropical deep reservoir.
AB  - Microorganisms play pivotal roles within aquatic ecosystems, affecting their
      structure, functioning and services. However, little is known about the effects
      of water stratification and mixing on the aquatic microbial community dynamics in
      subtropical reservoirs. In this study, we explored vertical and seasonal patterns
      of microbial diversity in the Dongzhen Reservoir (southeast China). Quantitative
      PCR, quantitative RT-PCR, and 454 pyrosequencing were used for an in-depth
      characterization of the bacterial community across time (every three months for
      one year) and space (five different water depths). Our results indicated that
      thermal and oxygen stratification shaped the phylogenetic composition of
      microbial communities in the reservoir. There were significant differences in
      physical, chemical and microbiological parameters between epilimnion and
      hypolimnion (P < 0.05). The RNA: DNA ratios were significantly lower in
      epilimnion and metalimnion but rapidly increased in hypolimnion (P < 0.05),
      suggesting that microorganisms were more active at low temperatures, low
      dissolved oxygen concentrations and high TN/TP ratios. Redundancy analysis and
      pathway analysis revealed a complex interplay of various environmental and
      biological factors by explaining the spatiotemporal variations in bacterial
      communities. Adaptive reservoir management strategies should consider carefully
      the effects of water stratification and mixing, together with the distribution
      patterns of aquatic microorganisms. 

PMID- 25059242
TI  - A pilot study on mobile phones as a means to access maternal health education in
      eastern rural Uganda.
AB  - Maternal mortality in Uganda has remained relatively high since 2006. We studied
      access to mobile phones and people's interest in receiving audio-based maternal
      health lessons delivered via a toll-free telephone line. Interviews were
      conducted, using a male and a female translator, with 42 men and 41 women in four
      villages located in eastern rural Uganda. Most of the participants were recruited
      through systematic sampling, but some were recruited through community
      organizations and antenatal clinics. Ownership of a mobile phone was reported by
      79% of men and by 42% of women. Among those who did not own a mobile phone, 67%
      of men and 88% of women reported regularly borrowing a mobile phone. Among women,
      98% reported interest in receiving maternal mobile health lessons, and 100% of
      men. Providing local communities with mobile maternal health education offers a
      new potential method of reducing maternal mortality. 

PMID- 25059243
TI  - Management of psychiatric appointments by telephone.

PMID- 25059244
TI  - The Dr Pheo Blog and virtual counselling for rare diseases.
AB  - Patients with suspected or diagnosed rare diseases face challenges. Their own
      physicians usually do not have a large experience in a particular rare disease,
      specialists may not be easily accessible, and medical knowledge on rare diseases
      is either not readily available or too general to be applied to the patients'
      individual situations. As a specialist with experience in pheochromocytoma, I
      therefore started a blog to disseminate knowledge about the tumour and to discuss
      readers' questions about it (http://drpheo.blogspot.com/). Between 2009 and 2014,
      the blog was viewed 81,223 times and received 1286 comments during the 5-year
      period. About half of the comments contained mostly questions (questioning
      comments), including 429 directly on pheochromocytoma (7.5/month). The majority
      of the questioning comments were about the diagnosis (62%) and natural history
      (21%) of pheochromocytoma, with the remainder on management (14%) and follow-up
      or prognosis (4%). Many readers' comments started with encouraging words about
      the blog and remarked how difficult it was to find useful information on
      pheochromocytoma elsewhere. Experience with the Dr Pheo Blog suggests that
      physician specialist-written blogs are potentially an effective and convenient
      way of providing pertinent knowledge on rare diseases to the public. 

PMID- 25059245
TI  - Feasibility of smartphone-delivered diabetes self-management education and
      training in an underserved urban population of adults.

PMID- 25059246
TI  - An economic analysis of a nurse-led telephone triage service.
AB  - Telephone nurse lines help callers to select the most appropriate site and level
      of care for acute conditions. We examined whether compliance with nurse
      recommendations was associated with lower average health care expenditure, and
      identified the employer characteristics associated with higher than average
      savings. Telephone calls to a nurse-led help line made by commercial health plan
      members who worked for large employers were identified. The callers' intention
      before calling and the nurse recommendation regarding site/level of care were
      recorded. Compliance was determined using medical claims during a 30-day post
      call observation period and was based on adherence to nurse recommendations. A
      total of 132,509 calls during 2012 were identified for the study. Nurse
      recommendations were that 31% of the callers seek a higher level of care than
      mentioned at the start of the call, 25% use a lower level of care and 44% pursue
      their originally intended level of care. After regression-based adjustment, the
      average medical expenditures were compared between compliers and non-compliers.
      Overall, 57% of callers were compliant with nurse recommendations. The average
      expenditures were $328 lower among compliant callers. A logistic regression
      analysis identified employer characteristics positively associated with achieving
      higher than average savings. These were having a low employee-to-dependent ratio,
      a headquarters in the Western region of the US, a low prospective health risk
      score, and participation by the employer in a targeted communication campaign.
      Compliance with the triage recommendations resulted in lower average health care
      expenditures, and several characteristics were positively associated with
      achieving higher savings.

PMID- 25059247
TI  - Developing clinical cancer genetics services in resource-limited countries: the
      case of retinoblastoma in Kenya.
AB  - BACKGROUND/AIMS: Clinical cancer genetics is an integral part of cancer control
      and management, yet its development as an essential medical service has been
      hindered in many low-and-middle-income countries. We report our experiences in
      developing a clinical cancer genetics service for retinoblastoma in Kenya.
      METHODS: A genetics task force was created from within the membership of the
      existing Kenyan National Retinoblastoma Strategy group. The task force engaged in
      multiple in-person and telephone discussions, delineating experiences, opinions
      and suggestions for an evidence-based, culturally sensitive retinoblastoma
      genetics service. Discussions were recorded and thematically categorized to
      develop a strategy for the design and implementation of a national retinoblastoma
      clinical genetics service. RESULTS: Discussion among the retinoblastoma genetics
      task force supported the development of a comprehensive genetics service that
      rests on 3 pillars: (1) patient and family counseling, (2) community involvement,
      and (3) medical education. CONCLUSIONS: A coordinated national retinoblastoma
      genetics task force led to the creation of a unique and relevant approach to
      delivering comprehensive and accurate genetic care to Kenyan retinoblastoma
      patients. The task force aims to stimulate innovative approaches in cancer
      genetics research, education and knowledge translation, taking advantage of
      unique opportunities offered in the African context.

PMID- 25059248
TI  - Comparison of the rheological properties of four root canal sealers.
AB  - The flowability of a root canal sealer is clinically important because it
      improves the penetration of the sealer into the complex root canal system. The
      purpose of this study was to compare the flowabilities of four root canal
      sealers, measured using the simple press method (ISO 6876), and their
      viscosities, measured using a strain-controlled rheometer. A newly developed,
      calcium phosphate-based root canal sealer (Capseal) and three commercial root
      canal sealers (AH Plus, Sealapex and Pulp Canal Sealer EWT) were used in this
      study. The flowabilities of the four root canal sealers were measured using the
      simple press method (n=5) and their viscosities were measured using a strain
      controlled rheometer (n=5). The correlation between these two values was
      statistically analysed using Spearman's correlation test. The flow diameters and
      the viscosities of the root canal sealers were strongly negatively correlated
      (rho=-0.8618). The viscosity of Pulp Canal Sealer EWT was the lowest and
      increased in the following order: AH Plus<Sealapex<Capseal (P<0.05). All of the
      tested root canal sealers showed characteristic time- and temperature-dependent
      changes in their rheological properties. The viscosities measured using the
      strain-controlled rheometer were more precise than the flowabilities measured
      using the simple press method, suggesting that the rheometer can accurately
      measure the rheological properties of root canal sealers. 

PMID- 25059249
TI  - Surface roughness of zirconia for full-contour crowns after clinically simulated
      grinding and polishing.
AB  - The aim of this study was to evaluate the effect of controlled intraoral grinding
      and polishing on the roughness of full-contour zirconia compared to classical
      veneered zirconia. Thirty bar-shaped zirconia specimens were fabricated and
      divided into two groups (n=15). Fifteen specimens (group 1) were glazed and 15
      specimens (group 2) were veneered with feldspathic ceramic and then glazed. Prior
      to grinding, maximum roughness depth (Rmax) values were measured using a
      profilometer, 5 times per specimen. Simulated clinical grinding and polishing
      were performed on the specimens under water coolant for 15 s and 2 N pressure.
      For grinding, NTI diamonds burs with grain sizes of 20 um, 10 um, and 7.5 um were
      used sequentially. The ground surfaces were polished using NTI kits with coarse,
      medium and fine polishers. After each step, Rmax values were determined.
      Differences between groups were examined using one-way analysis of variance
      (ANOVA). The roughness of group 1 was significantly lower than that of group 2.
      The roughness increased significantly after coarse grinding in both groups. The
      results after glazing were similar to those obtained after fine grinding for non
      veneered zirconia. However, fine-ground veneered zirconia had significantly
      higher roughness than venerred, glazed zirconia. No significant difference was
      found between fine-polished and glazed zirconia, but after the fine polishing of
      veneered zirconia, the roughness was significantly higher than after glazing. It
      can be concluded that for full-contour zirconia, fewer defects and lower
      roughness values resulted after grinding and polishing compared to veneered
      zirconia. After polishing zirconia, lower roughness values were achieved compared
      to glazing; more interesting was that the grinding of glazed zirconia using the
      NTI three-step system could deliver smooth surfaces comparable to untreated
      glazed zirconia surfaces.

PMID- 25059250
TI  - The clinical effectiveness of reflectance optical spectroscopy for the in vivo
      diagnosis of oral lesions.
AB  - Optical spectroscopy devices are being developed and tested for the screening and
      diagnosis of oral precancer and cancer lesions. This study reports a device that
      uses white light for detection of suspicious lesions and green-amber light at 545
      nm that detect tissue vascularity on patients with several suspicious oral
      lesions. The clinical grading of vascularity was compared to the histological
      grading of the biopsied lesions using specific biomarkers. Such a device, in the
      hands of dentists and other health professionals, could greatly increase the
      number of oral cancerous lesions detected in early phase. The purpose of this
      study is to correlate the clinical grading of tissue vascularity in several oral
      suspicious lesions using the Identafi((r)) system with the histological grading
      of the biopsied lesions using specific vascular markers. Twenty-one patients with
      various oral lesions were enrolled in the study. The lesions were visualized
      using Identafi((r)) device with white light illumination, followed by
      visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied
      was obtained from the all lesions and both histopathological and
      immunohistochemical studies using a vascular endothelial biomarker (CD34) were
      performed on these tissue samples. The clinical vascular grading using the green
      amber light at 545 nm and the expression pattern and intensity of staining for
      CD34 in the different biopsies varied depending on lesions, grading ranged from 1
      to 3. The increase in vascularity was observed in abnormal tissues when compared
      to normal mucosa, but this increase was not limited to carcinoma only as
      hyperkeratosis and other oral diseases, such as lichen planus, also showed
      increase in vascularity. Optical spectroscopy is a promising technology for the
      detection of oral mucosal abnormalities; however, further investigations with a
      larger population group is required to evaluate the usefulness of these devices
      in differentiating benign lesions from potentially malignant lesions.

PMID- 25059253
TI  - Design of smart home sensor visualizations for older adults.
AB  - BACKGROUND: Smart home sensor systems provide a valuable opportunity to
      continuously and unobtrusively monitor older adult wellness. However, the density
      of sensor data can be challenging to visualize, especially for an older adult
      consumer with distinct user needs. OBJECTIVE: We describe the design of sensor
      visualizations informed by interviews with older adults. The goal of the
      visualizations is to present sensor activity data to an older adult consumer
      audience that supports both longitudinal detection of trends and on-demand
      display of activity details for any chosen day. METHODS: The design process is
      grounded through participatory design with older adult interviews during a six
      month pilot sensor study. Through a secondary analysis of interviews, we
      identified the visualization needs of older adults. We incorporated these needs
      with cognitive perceptual visualization guidelines and the emotional design
      principles of Norman to develop sensor visualizations. RESULTS: We present a
      design of sensor visualization that integrate both temporal and spatial
      components of information. The visualization supports longitudinal detection of
      trends while allowing the viewer to view activity within a specific
      date.CONCLUSIONS: Appropriately designed visualizations for older adults not only
      provide insight into health and wellness, but also are a valuable resource to
      promote engagement within care.

PMID- 25059252
TI  - The distal radius fracture: concomitant fractures and their relevancy.
AB  - BACKGROUND: The distal radius keeps heading the list of commonly fractured bones.
      Although little is known about the frequency and localization of accompanying
      fractures as well as their influence on the total course of in-patient treatment.
      OBJECTIVE: This study is supposed to show the influence of concomitant fractures.
      These fractures should be identified as risk factors for a prolonged stay to
      improve the in hospital treatment. METHODS: We retrospectively reviewed 721
      patients with distal radius fracture. Frequency and localization of concomitant
      fractures, AO-type, patient age as well as duration of in-hospital treatment were
      analyzed. RESULTS: Out of 721 patients 124 (17.2%) had one or more concomitant
      fractures (CF). The most common CF were proximal femur fractures, pelvic ring
      fractures and humerus fractures. Compared to patients without CF, these patients
      showed a significant increase in duration of post operative hospital stay (5.2
      vs. 12.5 days, p=0.0001). CONCLUSIONS: Patients presenting a concomitant fracture
      should be thoroughly cared for by their physicians and therapists. Especially an
      early and focused mobilization and a well-timed relocation for further medical
      treatment are important to reduce avoidable treatment days in the acute care
      hospital.

PMID- 25059251
TI  - Metabolic activity of Streptococcus mutans biofilms and gene expression during
      exposure to xylitol and sucrose.
AB  - The objective of the study was to analyse Streptococcus mutans biofilms grown
      under different dietary conditions by using multifaceted methodological
      approaches to gain deeper insight into the cariogenic impact of carbohydrates. S.
      mutans biofilms were generated during a period of 24 h in the following media:
      Schaedler broth as a control medium containing endogenous glucose, Schaedler
      broth with an additional 5% sucrose, and Schaedler broth supplemented with 1%
      xylitol. The confocal laser scanning microscopy (CLSM)-based analyses of the
      microbial vitality, respiratory activity (5-cyano-2,3-ditolyl tetrazolium
      chloride, CTC) and production of extracellular polysaccharides (EPS) were
      performed separately in the inner, middle and outer biofilm layers. In addition
      to the microbiological sample testing, the glucose/sucrose consumption of the
      biofilm bacteria was quantified, and the expression of glucosyltransferases and
      other biofilm-associated genes was investigated. Xylitol exposure did not inhibit
      the viability of S. mutans biofilms, as monitored by the following experimental
      parameters: culture growth, vitality, CTC activity and EPS production. However,
      xylitol exposure caused a difference in gene expression compared to the control.
      GtfC was upregulated only in the presence of xylitol. Under xylitol exposure,
      gtfB was upregulated by a factor of 6, while under sucrose exposure, it was
      upregulated by a factor of three. Compared with glucose and xylitol, sucrose
      increased cell vitality in all biofilm layers. In all nutrient media, the
      intrinsic glucose was almost completely consumed by the cells of the S. mutans
      biofilm within 24 h. After 24 h of biofilm formation, the multiparametric
      measurements showed that xylitol in the presence of glucose caused predominantly
      genotypic differences but did not induce metabolic differences compared to the
      control. Thus, the availability of dietary carbohydrates in either a pure or
      combined form seems to affect the cariogenic potential of S. mutans biofilms. 

PMID- 25059254
TI  - Segmentation for the enhancement of microcalcifications in digital mammograms.
AB  - Microcalcification clusters appear as groups of small, bright particles with
      arbitrary shapes on mammographic images. They are the earliest sign of breast
      carcinomas and their detection is the key for improving breast cancer prognosis.
      But due to the low contrast of microcalcifications and same properties as noise,
      it is difficult to detect microcalcification. This work is devoted to developing
      a system for the detection of microcalcification in digital mammograms. After
      removing noise from mammogram using the Discrete Wavelet Transformation (DWT), we
      first selected the region of interest (ROI) in order to demarcate the breast
      region on a mammogram. Segmenting region of interest represents one of the most
      important stages of mammogram processing procedure. The proposed segmentation
      method is based on a filtering using the Sobel filter. This process will identify
      the significant pixels, that belong to edges of microcalcifications.
      Microcalcifications were detected by increasing the contrast of the images
      obtained by applying Sobel operator. In order to confirm the effectiveness of
      this microcalcification segmentation method, the Support Vector Machine (SVM) and
      k-Nearest Neighborhood (k-NN) algorithm are employed for the classification task
      using cross-validation technique. 

PMID- 25059255
TI  - EMG-force relationship during static contraction: effects on sensor placement
      locations on biceps brachii muscle.
AB  - BACKGROUND: The relationship between surface electromyography (EMG) and force
      have been the subject of ongoing investigations and remain a subject of
      controversy. Even under static conditions, the relationships at different sensor
      placement locations in the biceps brachii (BB) muscle are complex. OBJECTIVE: The
      aim of this study was to compare the activity and relationship between surface
      EMG and static force from the BB muscle in terms of three sensor placement
      locations. METHODS: Twenty-one right hand dominant male subjects (age 25.3+/-1.2
      years) participated in the study. Surface EMG signals were detected from the
      subject's right BB muscle. The muscle activation during force was determined as
      the root mean square (RMS) electromyographic signal normalized to the peak RMS
      EMG signal of isometric contraction for 10 s. The statistical analysis included
      linear regression to examine the relationship between EMG amplitude and force of
      contraction [40-100% of maximal voluntary contraction (MVC)], repeated measures
      ANOVA to assess differences among the sensor placement locations, and coefficient
      of variation (CoV) for muscle activity variation. RESULTS: The results
      demonstrated that when the sensor was placed on the muscle belly, the linear
      slope coefficient was significantly greater for EMG versus force testing
      (r2=0.62, P<0.05) than when placed on the lower part (r2=0.31, P>0.05) and upper
      part of the muscle belly (r2=0.29, P<0.05). In addition, the EMG signal activity
      on the muscle belly had less variability than the upper and lower parts (8.55%
      vs. 15.12% and 12.86%, respectively). CONCLUSION: These findings indicate the
      importance of applying the surface EMG sensor at the appropriate locations that
      follow muscle fiber orientation of the BB muscle during static contraction. As a
      result, EMG signals of three different placements may help to understand the
      difference in the amplitude of the signals due to placement.

PMID- 25059256
TI  - Skull removal in MR images using a modified artificial bee colony optimization
      algorithm.
AB  - Removal of the skull from brain Magnetic Resonance (MR) images is an important
      preprocessing step required for other image analysis techniques such as brain
      tissue segmentation. In this paper, we propose a new algorithm based on the
      Artificial Bee Colony (ABC) optimization algorithm to remove the skull region
      from brain MR images. We modify the ABC algorithm using a different strategy for
      initializing the coordinates of scout bees and their direction of search.
      Moreover, we impose an additional constraint to the ABC algorithm to avoid the
      creation of discontinuous regions. We found that our algorithm successfully
      removed all bony skull from a sample of de-identified MR brain images acquired
      from different model scanners. The obtained results of the proposed algorithm
      compared with those of previously introduced well known optimization algorithms
      such as Particle Swarm Optimization (PSO) and Ant Colony Optimization (ACO)
      demonstrate the superior results and computational performance of our algorithm,
      suggesting its potential for clinical applications. 

PMID- 25059257
TI  - Primary synovial chondromatosis of the hip - is arthroscopy sufficient? A review
      of the literature and a case report.
AB  - The purpose of this article was to evaluate the different techniques of operative
      treatment of primary synovial chondromatosis (PSC) of the hip. We performed a
      systematic review of literature of PSC and also present one case report about
      arthroscopic treatment of PSC. Our study compares both established operative
      procedures, open versus arthroscopic surgery, and shows each advantages and
      complications. One hundred and forty-seven publications were found in a PubMed
      literature review searching the terms: "synovial chondromatosis", "synovial
      osteochondromatosis", "synovial metaplasia" and "hip". All included studies were
      divided into open surgery or arthroscopic surgery concerning the therapeutic
      strategy and the corresponding results. We could find a total number of 3 reviews
      about PSC of the hip relating to operative procedures. One patient presented to
      our outpatient clinic with PSC. After other pathologies causing hip pain were
      excluded, the patient underwent hip arthroscopy with excision of the loose bodies
      and partial synovectomy. Diagnosis of PSC was confirmed by histopathology. The
      patient was examined before and one year after surgery with the Visual Analogue
      Scale (VAS) and the Hip Outcome Score (HOS ADL). Resecting PSC by hip arthroscopy
      is a minor surgical, but demanding procedure with minimal risks, even useful in
      the treatment of elderly patients with moderate osteoarthritis. 

PMID- 25059258
TI  - Breathing-phase selective filtering of respiratory data improves analysis of
      dynamic respiratory mechanics.
AB  - BACKGROUND: The analysis of non-linear respiratory system mechanics under the
      dynamic conditions of controlled mechanical ventilation is affected by systemic
      disturbances of the respiratory signals. Cardio-pulmonary coupling induces
      cardiogenic oscillations to the respiratory signals, which appear prominently in
      the second half of expiration. OBJECTIVE: We hypothesized that breathing phase
      selective filtering of expiratory data improves the analysis of respiratory
      system mechanics. METHODS: We retrospectively analyzed data from a multicenter
      study (28 patients with injured lungs, under volume-controlled ventilation) and
      from two additional studies (3 lung healthy patients and 3 with injured lungs,
      under pressure-controlled ventilation). Data streams were recorded at different
      levels of positive end-expiratory pressure. Using the gliding-SLICE method,
      intratidal dynamic respiratory mechanics were analyzed with and without low-pass
      filtering of expiratory or inspiratory data separately. The quality of data
      analysis was derived from the coefficient of determination R^2. RESULTS: Without
      filtering, R^2 lay below 0.995 for 87 of 280 investigated data streams. In 68
      cases expiration-selective low-pass filtering improved the quality of analysis to
      R^2 ? 0.995. In contrast, inspiration-selective filtering did not improve R^2.
      CONCLUSIONS: The selective filtering of expiration data eliminates negative side
      effects of cardiogenic oscillations thus leading to a significant improvement of
      the analysis of dynamic respiratory system mechanics.

PMID- 25059259
TI  - Diversity of extradiol dioxygenases in aromatic-degrading microbial community
      explored using both culture-dependent and culture-independent approaches.
AB  - Culture-dependent and culture-independent approaches were used for extensive
      retrieval of the extradiol dioxygenase (EDO) gene from the environment to
      investigate the relationship between the EDO genes from isolated bacteria and the
      metagenomic EDO genes from which they were isolated. In our previous study, we
      identified 91 fosmid clones showing EDO enzyme activity using a metagenomic
      approach. In the present study, we classified all these metagenome-derived EDOs
      and newly isolated 88 phenol-utilizing bacteria from the same sample and
      identified four EDO genes from them. Of these, two EDOs had amino acid sequences
      similar to those reported previously in aromatic-utilizing strains, and one EDO
      had a sequence almost identical to that of metagenomic EDOs identified in our
      previous study. Unexpectedly, one EDO showed no similarity to any class I EDOs
      and was categorized as class II, which has not been found in past metagenomic
      approaches. Quantitative polymerase chain reaction (PCR) assay indicated that the
      low-abundance class II EDO gene can be enriched by culturing approaches. We
      conclude that the combined use of the two approaches can explore the gene
      community more extensively than their individual use. 

PMID- 25059260
TI  - Beyond psychosis risk: early clinical phenotypes in mental disorder and the
      subthreshold pathway to safe, timely and effective care.

PMID- 25059262
TI  - A Hybridized GA with LP-LP Model for the Management of Confined Groundwater.
AB  - A novel hybrid methodology is introduced in this paper for the optimal solution
      of the groundwater management problem. The problem to be addressed is the optimal
      determination and operation of a predefined number of wells out of a priori known
      set of potential wells with fixed locations to minimize the pumping cost of
      utilizing a two-dimensional (2D) confined aquifer under steady-state flow
      condition. The solution to this problem should satisfy a downstream demand, a
      lower/upper bound on the pumping rates, and a lower/upper bound on the water
      level drawdown in the wells. The problem is solved by hybridizing a genetic
      algorithm (GA) which suggests the candidate configurations for the operational
      wells and a hybrid linear programming (LP-LP) approach with the duty of finding
      the optimal operation policy of the candidate wells defined by their pumping
      rates. Two different codings, namely binary and integer codings, are used for the
      GA and their performances are compared. The ability of the proposed hybrid method
      is tested against two benchmark problems: (1) finding the optimal configuration
      and pumping rates of a predefined number of wells out of potential wells and (2)
      finding the optimal number, configuration and pumping rates of the operating
      wells out of potential wells and the results are presented and compared with the
      available ones showing superior efficiency and effectiveness of the proposed
      method. 

PMID- 25059261
TI  - Prenatal alcohol exposure and adolescent stress - unmasking persistent
      attentional deficits in rats.
AB  - Prenatal alcohol exposure (PAE) can produce a myriad of deficits. Unfortunately,
      affected individuals may also be exposed to the stress of an adverse home
      environment, contributing to deficits of attentional processes that are the
      hallmark of optimal executive function. Male offspring of ad-libitum-fed Control
      (Con), Pairfed (PF), and PAE dams were randomly assigned to either a 5-day period
      of variable chronic mild stress (CMS) or no CMS in adolescence. In adulthood,
      rats were trained in a non-match to sample task (T-maze), followed by extensive
      assessment in the five-choice serial reaction time task. Once rats acquired the
      five-choice serial reaction time task (stable accuracy), they were tested in
      three challenge conditions: (i) increased sustained attention, (ii) selective
      attention and, (iii) varying doses of d-amphetamine, an indirect dopamine and
      norepinephrine agonist. At birth and throughout the study, PAE offspring showed
      reduced body weight. Moreover, although PAE animals were similar to Con animals
      in task acquisition, they were progressively less proficient with transitions to
      shorter stimulus durations (decreased accuracy and increased omissions). Five
      days of adolescent CMS increased basal corticosterone levels in adolescence and
      disrupted cognitive performance in adulthood. Further, CMS augmented PAE-related
      disturbances in acquisition and, to a lesser extent, also disrupted attentional
      processes in Con and PF animals. Following task acquisition, challenges unmasked
      persistent attentional difficulties resulting from both PAE and adolescent CMS.
      In conclusion, PAE, adolescent CMS, and their interaction produced unique
      behavioural profiles that suggest vulnerability in select neurobiological
      processes at different stages of development. 

PMID- 25059263
TI  - Feasibility and preliminary effectiveness of a novel cognitive-behavioral couple
      therapy for provoked vestibulodynia: a pilot study.
AB  - INTRODUCTION: Provoked vestibulodynia (PVD), a recurrent, localized vulvovaginal
      pain problem, carries a significant psychosexual burden for afflicted women, who
      report impoverished sexual function and decreased frequency of sexual activity
      and pleasure. Interpersonal factors such as partner responses to pain, partner
      distress, and attachment style are associated with pain outcomes for women and
      with sexuality outcomes for both women and partners. Despite these findings, no
      treatment for PVD has systematically included the partner. AIMS: This study pilot
      tested the feasibility and potential efficacy of a novel cognitive-behavioral
      couple therapy (CBCT) for couples coping with PVD. METHODS: Couples (women and
      their partners) in which the woman was diagnosed with PVD (N = 9) took part in a
      12-session manualized CBCT intervention and completed outcome measures pre- and
      post-treatment. MAIN OUTCOME MEASURES: The primary outcome measure was women's
      pain intensity during intercourse as measured on a numerical rating scale.
      Secondary outcomes included sexual functioning and satisfaction for both
      partners. Exploratory outcomes included pain-related cognitions; psychological
      outcomes; and treatment satisfaction, feasibility, and reliability. RESULTS: One
      couple separated before the end of therapy. Paired t-test comparisons involving
      the remaining eight couples demonstrated significant improvements in women's pain
      and sexuality outcomes for both women and partners. Exploratory analyses
      indicated improvements in pain-related cognitions, as well as anxiety and
      depression symptoms, for both members of the couple. Therapists' reported high
      treatment reliability and participating couples' high participation rates and
      reported treatment satisfaction indicate adequate feasibility. CONCLUSIONS:
      Treatment outcomes, along with treatment satisfaction ratings, confirm the
      preliminary success of CBCT in reducing pain and psychosexual burden for women
      with PVD and their partners. Further large-scale randomized controlled trials are
      necessary to examine the efficacy of CBCT compared with and in conjunction with
      first-line biomedical interventions for PVD.

PMID- 25059264
TI  - [Effect of lacosamide on the quality of life of patients with epilepsy].
AB  - INTRODUCTION: Epilepsy causes psychiatric disorders in 20-40% of patients
      impacting negatively on their quality of life. Lacosamide is a new antiepileptic
      as adjunctive therapy in partial seizures with or without generalization. AIM: We
      conducted a study to assess the impact of lacosamide as to the quality of life of
      epileptic patients. We used the HAD scale for anxiety and depression and QOLIE-10
      scale for quality of life. We evaluated the efficacy and tolerability. PATIENTS
      AND METHODS: We collected prospectively poorly controlled epileptic patients are
      and added lacosamide treatment. Baseline visit, at 3 and 6 months were performed.
      The questionnaires are completed and the epilepsy information has been collected.
      RESULTS: 31 patients, age 45.5 +/- 17.2 years, 64.5% males are included. Number
      of previous monthly crisis 1.6 +/- 1.8. HAD anxiety scale shows a significant
      improvement at 3 and 6 months. HAD scale for depression reflects a significant
      improvement in quality parameters. QOLIE-10 shows significant improvement for the
      group with low quality of life after 3 and 6 months. After 6 months 61.3% of
      patients have a seizure reduction equal or more than 50% and 54.8% are seizure
      free. Dizziness is the most common side effect (22.8%). 74.2% continued
      treatment. CONCLUSIONS: Lacosamide may improve anxiety, depression and quality of
      life of epileptic patients regardless of seizure control. Response to treatment,
      adherence and side effects are similar to previous studies.

PMID- 25059265
TI  - [Stroke in paediatric patients with sickle-cell anaemia].
AB  - INTRODUCTION: Sickle-cell anaemia is the severe homozygotic form of
      drepanocytosis, a genetic disorder that often occurs among black people and which
      is characterised by the production of haemoglobin S, chronic hemolytic anaemia
      and tissue ischaemia due to alterations in blood flow. A quarter of the patients
      presented neurological manifestations; 8-10% of children will have a stroke. AIM.
      To analyse the cases of stroke in children with sickle-cell anaemia in our
      centre. PATIENTS AND METHODS: We conducted a retrospective descriptive study of
      children with sickle-cell anaemia and stroke. RESULTS: Five patients (two
      Dominicans and three Guineans) with sickle-cell anaemia and stroke; one patient
      suffered two episodes of stroke. The mean age was 27 months. Five of the episodes
      were ischaemic infarctions. Stroke was the initial form of presentation of
      drepanocytosis on three occasions. Two of the strokes occurred within a context
      of pneumococcal meningitis. Four of the patients had previously reported fever.
      The initial clinical picture was hemiparesis in four cases. Mean haemoglobin on
      diagnosing the stroke was 6.5 g/dL. Transcranial ultrasound imaging revealed
      alterations in three patients and, in all the patients, magnetic resonance
      imaging revealed lesions, which were bilateral in half the cases. Following the
      stroke, a hypertransfusion regimen protocol was established and only one patient
      presented a new stroke. This same patient went on to develop moya-moya disease
      and was submitted to an indirect revascularisation; the patient progressed well,
      without presenting any new ischaemic events. CONCLUSIONS: Drepanocytosis is a
      disease that is emerging in our setting as a result of immigration. It should be
      suspected in cases of paediatric strokes associated to anaemia, above all in
      black children under the age of five who were not submitted to neonatal
      screening.

PMID- 25059266
TI  - [Diploid/triploid mosaicism: a variable but characteristic phenotype].
AB  - INTRODUCTION: Diploid/triploid mosaicism is a rare chromosomal abnormality. It is
      caused by a failure in the postzygotic division during embryonic development. It
      results in the coexistence of two genetically heterogeneous cell lines (46,XX and
      69,XXX) in one individual. His clinical phenotype is characteristic. Pigmentary
      changes with a distribution pattern following Blaschko's lines abnormalities in
      other ectoderm-derived tissues are the main diagnostic signs. CASE REPORTS: Three
      cases of diploid/triploid mosaicism are described, and compared to the previously
      reported cases. The most frequently observed symptoms were mental retardation,
      truncal obesity, short stature, hemihypertrophy, small and narrow hands with
      clino and camptodactyly. Phenotypic characteristics of our three patients were
      similar to those of previously reported cases. Although there is no single and
      specific phenotype associated with mosaicism diploid/triploid, there are some
      dysmorphic features that shape a recognizable malformative syndrome. Peripheral
      blood lymphocytes karyotype was normal in our patients. Diagnosis was reached
      performing a fibroblast karyotype from hypopigmented skin. CONCLUSIONS:
      Intellectual disability associated with truncal obesity, short stature,
      hemihypertrophy or clino/camptodactyly should suggest to clinicians the possible
      existence of a diploid/triploid mosaicism. In most cases, karyotype from
      fibroblasts is needed to reach the diagnosis.

PMID- 25059267
TI  - [Pharmacotherapy for tinnitus: much ado about nothing].
AB  - INTRODUCTION: Chronic tinnitus affects 5-15% of the general population; in 1% of
      individuals with tinnitus this condition severely affects their quality of life.
      Pharmacological treatment is one of the options for the management of tinnitus
      patients, but their efficacy remains controversial. AIM. To evaluate the level of
      evidence to support the use of different drugs in reducing the severity of
      tinnitus. DEVELOPMENT: The pharmacological groups that have been investigated for
      the treatment of tinnitus include anesthetics, anticonvulsants, antidepressants,
      antihistamines, benzodiazepines, diuretics, corticosteroids, and of other
      substances. Intravenous lidocaine seems to be effective, but the short duration
      of the effect and the adverse reactions prevent its use. Compared with placebo,
      carbamazepine and gabapentine have not demonstrated effectiveness although they
      may be effective in some patients with auditory nerve vascular compression or
      myoclonus. Tricyclic antidepressants are no more effective than placebo at
      reducing tinnitus severity although they may improve comorbid depression. There
      is insufficient evidence to evaluate the effectiveness of selective serotonin
      reuptake inhibitors and benzodiazepines. Acamprosate may decrease the severity of
      tinnitus, but the level of evidence is low. There are no consistent results in
      the studies with intratympanic gentamicin or steroids in tinnitus associated with
      Meniere's disease. CONCLUSIONS: The use of pharmacotherapy in reducing the
      severity of tinnitus is not well supported by prospective, randomized, placebo
      controlled clinical trials. Various drugs have been shown to be effective in some
      studies, but the clinical evidence is limited. Large randomized clinical trials
      are needed.

PMID- 25059268
TI  - [Effectiveness of transcranial ultrasound in deep brain stimulation].

PMID- 25059270
TI  - [Is a specific on-call stroke service useful?].

PMID- 25059271
TI  - [Inflation of the prefix 'neuro' and devaluation of neurology?].

PMID- 25059273
TI  - Prenatal imaging of a fetus with the rare combination of a right congenital
      diaphragmatic hernia and a giant omphalocele.
AB  - A co-existing right congenital diaphragmatic hernia and omphalocele is rare. We
      present images of a fetus diagnosed with this rare combination of anomalies.
      Early neonatal death occurred immediately after full-term birth due to severe
      respiratory insufficiency. In this case, disturbance of chest wall development
      due to the omphalocele rather than the diaphragmatic hernia was considered as the
      main cause of lung hypoplasia. Our experience suggests that caution should be
      exercised for severe respiratory insufficiency in a neonate with an omphalocele
      and diaphragmatic hernia, even in the absence of an intra-thoracic liver, one of
      the indicators of poor outcome for congenital diaphragmatic hernia. 

PMID- 25059272
TI  - miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1
      downregulation.
AB  - Increasing evidence suggests that microRNAs (miRNAs) play important roles in
      impaired endothelial cell (EC) angiogenesis during aging. However, their exact
      roles in the aging process remain unclear. We aimed to determine whether miRNAs
      cause angiogenesis defects in ECs during aging and to uncover the underlying
      mechanisms. To study the miRNA-induced changes in ECs during aging, we performed
      microarray analyses on arterial ECs collected from young and aging mice. Using
      qRT-PCR, we showed that microRNA-125a-5p (mir-125a-5p) expression was
      approximately 2.9 times higher in old endothelial cells (OECs) compared with
      samples collected from young animals. Western blot assays showed a lower
      expression level of an mir-125a-5p target known as related transcriptional
      enhancer factor-1 (RTEF-1) in OECs compared with its expression levels in young
      cells. Overexpression of mir-125a-5p in young endothelial cells (YECs) using pre
      mir-125a-5p caused the downregulation of RTEF-1, endothelial nitric oxide
      synthase (eNOS) and vascular endothelial growth factor (VEGF) and resulted in
      impaired angiogenesis, as evidenced by spheroid sprouting and tube formation
      assays in vitro. Conversely, repression of mir-125a-5p in OECs using anti-mir
      125a-5p increased RTEF-1, eNOS and VEGF expression and improved EC angiogenesis.
      Importantly, impaired angiogenesis caused by knock-down of RTEF-1 was not
      efficiently rescued by anti-mir-125a-5p. Dual-luciferase reporter gene analysis
      showed that RTEF-1 is a direct target of mir-125a-5p, which regulates
      angiogenesis by repressing RTEF-1 expression and modulating eNOS and VEGF
      expression. These findings indicate that mir-125a-5p and RTEF-1 are potential
      therapeutic targets for improving EC-mediated angiogenesis in elderly
      individuals. 

PMID- 25059274
TI  - Polymer/TiO2 hybrid vesicles for excellent UV screening and effective
      encapsulation of antioxidant agents.
AB  - Presented in this paper is a hybrid polymer/titanium dioxide (TiO2) vesicle that
      has excellent UV-screening efficacy and strong capacity to encapsulate
      antioxidant agents. Poly(ethylene oxide)-block-poly(2-(dimethylamino)ethyl
      methacrylate)-block-polystyrene (PEO-b-PDMAEMA-b-PS) triblock terpolymer was
      synthesized by atom transfer radical polymerization (ATRP) and then self
      assembled into vesicles. Those vesicles showed excellent UV-screening property
      due to the scattering by vesicles and the absorption by PS vesicle membrane. The
      selective deposition of solvophobic tetrabutyl titanate in the PDMAEMA shell and
      the PS membrane of the vesicles led to the formation of polymer/TiO2 hybrid
      vesicles, resulting in an enhanced UV-screening property by further reflecting
      and scattering UV radiation. The vesicles can effectively encapsulate antioxidant
      agents such as ferulic acid (up to 57%), showing a rapid antioxidant capability
      (within 1 min) and a long-lasting antioxidant effect. 

PMID- 25059275
TI  - Prospective evaluation of the International Study Group for Liver Surgery
      definition of bile leak after a liver resection and the role of routine operative
      drainage: an international multicentre study.
AB  - BACKGROUND: The International Study Group for Liver Surgery (ISGLS) proposed a
      definition for bile leak after liver surgery. A multicentre international
      prospective study was designed to evaluate this definition. METHODS: Data
      collected prospectively from 949 consecutive patients on specific datasheets from
      11 international centres were collated centrally. RESULTS: Bile leak occurred in
      69 (7.3%) of patients, with 31 (3.3%), 32 (3.4%) and 6 (0.6%) classified as grade
      A, B and C, respectively. The grading system of severity correlated with the
      Dindo complication classification system (P < 0.001). Hospital length of stay was
      increased when bile leak occurred, from a median of 7 to 15 days (P < 0.001), as
      was intensive care stay (P < 0.001), and both correlated with increased severity
      grading of bile leak (P < 0.001). 96% of bile leaks occurred in patients with
      intra-operative drains. Drain placement did not prevent subsequent intervention
      in the bile leak group with a 5-15 times greater risk of intervention required in
      this group (P < 0.001). CONCLUSION: The ISGLS definition of bile leak after liver
      surgery appears robust and intra-operative drain usage did not prevent the need
      for subsequent drain placement.

PMID- 25059276
TI  - A tale worth telling: the impact of the diagnosis experience on disclosure of
      genetic disorders.
AB  - BACKGROUND: Research suggests children with genetic disorders exhibit greater
      coping skills when they are aware of their condition and its heritability. While
      the experiences parents have at diagnosis may influence their decision to
      disclose the diagnosis to their children, there is little research into this
      communication. The aim of the current study was to examine the relationship
      between the diagnosis experience and the disclosure experience for parents of
      children with developmental disorders of a known genetic aetiology: parents of
      children with 22q11.2 deletion syndrome (22q11DS) were compared with a group of
      parents with children affected with other genetic diagnoses, with a similar age
      of diagnosis (e.g. fragile X syndrome) and a group where diagnosis generally
      occurs early (i.e. Down syndrome). METHOD: The sample comprised 559 parents and
      caregivers of children with genetic developmental disorders, and an online survey
      was utilised. Items from the questionnaire were combined to create variables for
      diagnosis experience, parental disclosure experience, child's disclosure
      experience, and parental coping and self-efficacy. RESULTS: Across all groups
      parents reported that the diagnosis experience was negative and often accompanied
      by a lack of support and appropriate information. Sixty-eight per cent of those
      in the 22q11DS and 58.3% in the Similar Conditions groups had disclosed the
      diagnosis to their child, whereas only 32.7% of the Down syndrome group had.
      Eighty-six per cent of the Down syndrome group felt they had sufficient
      information to talk to their child compared with 44.1% of the Similar Conditions
      group and 32.6% of the 22q11DS group. Parents reported disclosing the diagnosis
      to their child because they did not want to create secrets; and that they
      considered the child's age when disclosing. In the 22q11DS and Similar Conditions
      groups, a poor diagnosis experience was significantly associated with negative
      parental disclosure experiences. In the Similar Conditions group, a poor
      diagnosis experience was also significantly associated with a more negative child
      disclosure experience. CONCLUSIONS: As expected this study highlights how
      difficult most parents find the diagnosis experience. Importantly, the data
      indicate that the personal experiences the parents have can have a long-term
      impact on how well they cope with telling their child about the diagnosis. It is
      important for clinicians to consider the long-term ramifications of the diagnosis
      experience and give the parents opportunities; through, for instance,
      psychoeducation to prepare for telling their child about the diagnosis. Further
      research is warranted to explore what type of information would be useful for
      parents to receive.

PMID- 25059277
TI  - A novel multi-strain probiotic and synbiotic supplement for prevention of
      Clostridium difficile infection in a murine model.
AB  - The protective effect of a multi-strain probiotic and synbiotic formulation was
      evaluated in C57BL/6 mice infected with Clostridium difficile (CD) NAP1/027.
      Antibiotic-treated mice were divided into the following four groups: Group 1, fed
      with a synbiotic formulation consisting of Lactobacillus plantarum F44, L.
      paracasei F8, Bifidobacterium breve 46, B. lactis 8:8, galacto-oligosaccharides,
      isomalto-oligosaccharides, and resistant starch; Group 2, fed with the same four
      probiotic strains as Group 1; Group 3, fed with the same prebiotic supplements as
      Group 1 for 7 days before CD infection; and Group 4 (control group) antibiotic
      treated and infected with NAP1/027 strain. Feces and cecal contents were
      collected for microbial cell viability, quantitative PCR (qPCR), toxin analyses
      and histopathology. Synbiotics- and probiotics-fed mice showed a significant
      increase in total bifidobacteria (P < 0.05). The total lactobacilli count was
      increased in Group 1. Tests for cecal toxins were negative in Group 2 mice,
      whereas one sample each from Group 1 and 3 was positive. qPCR of cecal contents
      showed significant reduction in NAP1/027 DNA copies in Groups 1 and 2 and
      significantly higher numbers of B. breve 46, L. plantarum F44, and L. paracasei
      F8 in Groups 1 and 2 (P < 0.05); these changes were much less pronounced in
      Groups 3 and 4. Our findings indicate that the newly developed synbiotic or multi
      strain probiotic formulation confers protection against NAP1/027 infection in
      C57BL/6 mice. This holds promise for performing human studies.

PMID- 25059278
TI  - Capicua is involved in Dorsal-mediated repression of zerknullt expression in
      Drosophila embryo.
AB  - The maternal transcription factor Dorsal (Dl) functions as both an activator and
      a repressor in a context-dependent manner to control dorsal-ventral patterning in
      the Drosophila embryo. Previous studies have suggested that Dl is an intrinsic
      activator and its repressive activity requires additional corepressors that bind
      corepressor-binding sites near Dl-binding sites. However, the molecular
      identities of the corepressors have yet to be identified. Here, we present
      evidence that Capicua (Cic) is involved in Dl-mediated repression in the
      zerknullt (zen) ventral repression element (VRE). Computational and genetic
      analyses indicate that a DNA-binding consensus sequence of Cic is highly
      analogous with previously identified corepressor-binding sequences and that Dl
      failed to repress zen expression in lateral regions of cic mutant embryos.
      Furthermore, electrophoretic mobility shift assay (EMSA) shows that Cic directly
      interacts with several corepressor-binding sites in the zen VRE. These results
      suggest that Cic may function as a corepressor by binding the VRE.

PMID- 25059279
TI  - Celastrol ameliorates cytokine toxicity and pro-inflammatory immune responses by
      suppressing NF-kappaB activation in RINm5F beta cells.
AB  - Upregulation of pro-inflammatory mediators contributes to beta-cell destruction
      and enhanced infiltration of immune cells into pancreatic islets during
      development of type 1 diabetes mellitus. In this study, we examined the
      regulatory effects and the mechanisms of action of celastrol against cytotoxicity
      and pro-inflammatory immune responses in the RINm5F rat pancreatic beta-cell line
      stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha,
      and interferon-gamma. Celastrol significantly restored cytokine-induced cell
      death and significantly inhibited cytokine-induced nitric oxide production. In
      addition, the protective effect of celastrol was correlated with a reduction in
      pro-inflammatory mediators, such as inducible nitric oxide synthase,
      cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly
      suppressed cytokine- induced signaling cascades leading to nuclear factor kappa B
      (NF-kappaB) activation, including IkappaB-kinase (IKK) activation, IkappaB
      degradation, p65 phosphorylation, and p65 DNA binding activity. These results
      suggest that celastrol may exert its cytoprotective activity by suppressing
      cytokine-induced expression of pro-inflammatory mediators by inhibiting
      activation of NF-kappaB in RINm5F cells.

PMID- 25059280
TI  - Oleanolic acid regulates NF-kappaB signaling by suppressing MafK expression in
      RAW 264.7 cells.
AB  - Oxidative stress and inflammation are common to many pathological conditions.
      Defense mechanisms protect cells from oxidative stress, but can become over
      activated following injury and inflammation. NF-kappaB and Nrf2 transcription
      factors regulate proinflammatory and antioxidant gene expression, respectively.
      Studies have shown that many natural dietary compounds regulate NF-kappaB and
      Nrf2, preventing inflammation and oxidative stress. Here, we report major
      compounds of Prunella vulgaris var. lilacina such as rosmarinic acid, oleanolic
      acid, ursolic acid and caffeic acid as a potential therapeutic for oxidative
      stress and inflammation. The major compounds exhibited high anti-inflammatory
      activity, inhibiting NO, PGE2 production, NF-kappaB expression and activating
      Nrf2 expression. In addition, we examined the effect of major compounds on MafK
      expression. Among the compounds, oleanolic acid significantly decreased MafK
      expression and MafK-mediated p65 acetylation. These findings suggest that
      oleanolic acid as NF-kappaB inhibitors can potentially be used in therapeutic
      applications for the treatment of oxidative stressnduced diseases.

PMID- 25059281
TI  - Hypotrichosis associated with capillary malformation-arteriovenous malformation
      syndrome.
AB  - BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome
      is associated with multifocal small CMs and a high risk for high-flow lesions. It
      is an autosomal dominant disorder, caused by RASA1 gene mutations. Recently, two
      novel clinical features have been identified: numerous small pale halos with
      central punctate red spots, and naevus anemicus. OBJECTIVES: To identify the
      prevalence of the new clinical manifestations in our patients with CM-AVM. The
      secondary objective was to investigate the presence of other skin lesions.
      METHODS: We retrospectively searched the picture database of our department for
      cases with a clinical diagnosis of CM-AVM, based on the identification of
      multiple cutaneous CMs and a negative history of epistaxis. We prospectively
      conducted a clinical and dermoscopic skin examination in all of these patients.
      RESULTS: Seven patients with multiple CMs were found, and only in one case was a
      cutaneous AVM present. Five patients had red punctate spots surrounded by pale
      halos on the upper limbs. Two adult patients also showed multiple telangiectasias
      on the neck and upper trunk. Naevus anemicus was not detected in any patient. A
      partial or total absence of vellous hair on the surface of CMs was observed in
      all patients. CONCLUSIONS: Red punctate spots with pale halos or small
      telangiectasias are frequent findings in CM-AVM syndrome. Hypotrichosis on the
      CMs suggests that RASA1 gene mutations could be involved in the hair follicle
      proliferation and cell cycle.

PMID- 25059282
TI  - Exploring pharmacological activities and signaling of morphinans substituted in
      position 6 as potent agonists interacting with the MU opioid receptor.
AB  - BACKGROUND: Opioid analgesics are the most effective drugs for the treatment of
      moderate to severe pain. However, they also produce several adverse effects that
      can complicate pain management. The MU opioid (MOP) receptor, a G protein-coupled
      receptor, is recognized as the opioid receptor type which primarily mediates the
      pharmacological actions of clinically used opioid agonists. The morphinan class
      of analgesics including morphine and oxycodone are of main importance as
      therapeutically valuable drugs. Though the natural alkaloid morphine contains a C
      6-hydroxyl group and the semisynthetic derivative oxycodone has a 6-carbonyl
      function, chemical approaches have uncovered that functionalizing position 6
      gives rise to a range of diverse activities. Hence, position 6 of N
      methylmorphinans is one of the most manipulated sites, and is established to play
      a key role in ligand binding at the MOP receptor, efficacy, signaling, and
      analgesic potency. We have earlier reported on a chemically innovative
      modification in oxycodone resulting in novel morphinans with 6-acrylonitrile
      incorporated substructures. RESULTS: This study describes in vitro and in vivo
      pharmacological activities and signaling of new morphinans substituted in
      position 6 with acrylonitrile and amido functions as potent agonists and
      antinociceptive agents interacting with MOP receptors. We show that the presence
      of a 6-cyano group in N-methylmorphinans has a strong influence on the binding to
      the opioid receptors and post-receptor signaling. One 6-cyano-N-methylmorphinan
      of the series was identified as the highest affinity and most selective MOP
      agonist, and very potent in stimulating G protein coupling and intracellular
      calcium release through the MOP receptor. In vivo, this MOP agonist showed to be
      greatly effective against thermal and chemical nociception in mice with marked
      increased antinociceptive potency than the lead molecule oxycodone. CONCLUSION:
      Development of such novel chemotypes by targeting position 6 provides valuable
      insights on ligand-receptor interaction and molecular mode of action, and may aid
      in identification of opioid therapeutics with enhanced analgesic properties and
      fewer undesirable effects.

PMID- 25059283
TI  - Characteristics of hyperparathyroid states in the Canadian multicentre
      osteoporosis study (CaMos) and relationship to skeletal markers.
AB  - CONTEXT: PTH is an essential regulator of mineral metabolism; PTH hypersecretion
      may result in hyperparathyroidism including normocalcaemic, primary and secondary
      hyperparathyroidism. OBJECTIVE: To examine the characteristics of participants
      with hyperparathyroid states and the relationship to bone mineral density (BMD).
      DESIGN AND PARTICIPANTS: A cross-sectional study of 1872 community-dwelling men
      and women aged 35+ years (mostly Caucasian) with available serum PTH from Year 10
      Canadian Multicentre Osteoporosis Study follow-up (2005-07). PTH was determined
      using a second-generation chemiluminescence immunoassay. OUTCOME MEASURES: L1-L4,
      femoral neck and total hip BMD. RESULTS: We established a PTH reference range
      (2.7-10.2 pmol/l) based on healthy participants (i.e. normal serum calcium, serum
      25-hydroxyvitamin D, kidney function and body mass index, who were nonusers of
      antiresorptives, glucocorticoids and diuretics and not diagnosed with diabetes or
      thyroid disease). Participants with PTH levels in the upper reference range (5.6
      10.2 pmol/l), representing a prevalence of 10.7%, had lower femoral neck and
      total hip BMD, by 0.030 g/cm(2) [95% confidence interval: 0.009; 0.051] and 0.025
      g/cm(2) (0.001; 0.049), respectively, than those with levels 2.7-5.6 pmol/l.
      Participants with normocalcaemic and secondary hyperparathyroidism also had lower
      total hip BMD than those with levels 2.7-5.6 pmol/l, and CaMos prevalences of
      normocalcaemic, primary and secondary hyperparathyroidism were 3.3%, 1.4% and
      5.2%, respectively. CONCLUSION: We found reduced BMD in participants with
      accepted hyperparathyroid states but also a notable proportion of other
      participants that might benefit from having lower PTH levels.

PMID- 25059284
TI  - Oxidative stress increases pulmonary vascular permeability in diabetic rats
      through activation of transient receptor potential melastatin 2 channels.
AB  - OBJECTIVE: In vitro superoxide activates pulmonary endothelial TRPM2 channels and
      increases Kf . We hypothesized that pulmonary capillary Kf is increased in a
      model of type I diabetes due to elevated vascular superoxide and resultant TRPM2
      channel activation. METHODS: Type I diabetes was induced in Zucker rats using
      STZ. Half of the STZ animals were treated with apocynin, a NOX inhibitor. After
      four weeks, lung Kf was measured in the isolated lung in the presence or absence
      of TRPM2 inhibitors (2-APB and FA). In an additional set of experiments, Kf was
      measured in nondiabetic Zucker rats after applying the superoxide donor (PMS).
      RESULTS: As compared to control rats, hyperglycemic rats exhibited increased
      vascular superoxide and Kf , along with decreased lung vascular TRPM2-L
      expression. Apocynin treatment reduced superoxide and Kf in hyperglycemic rats
      with no effect in control rats. TRPM2 channel inhibition decreased Kf in
      hyperglycemic rats with no effect in control rats. PMS increased the lung Kf in
      control rats, with TRPM2 inhibition attenuating this response. CONCLUSION:
      Diabetic rats exhibit a TRPM2-mediated increase in lung Kf , which is associated
      with increased TRPM2 activation and increased vascular superoxide levels.

PMID- 25059285
TI  - Definitions in hemophilia: communication from the SSC of the ISTH.

PMID- 25059286
TI  - The impact of diabetes mellitus on long-term clinical outcomes after percutaneous
      coronary saphenous vein graft interventions in the drug-eluting stent era.
AB  - OBJECTIVES: We aimed to compare early and late clinical outcomes in diabetic and
      nondiabetic patients who underwent saphenous vein graft (SVG) percutaneous
      coronary interventions (PCI) with the use of drug-eluting stents (DES).
      BACKGROUND: Patients with diabetes mellitus are shown to have less favorable
      outcomes after SVG intervention with the use of bare metal stents. In the DES
      era, the impact of diabetes mellitus on restenosis and clinical outcomes post-SVG
      intervention is not clearly defined. METHODS: From our institutional PCI registry
      database, we retrospectively analyzed 477 consecutive patients with prior
      coronary artery bypass graft surgery undergoing SVG PCI with the implantation of
      DES stratified by the presence or absence of diabetes mellitus. The primary end
      point was 1-year major adverse cardiac event (MACE) rate, defined as death, Q
      wave myocardial infarction, and target lesion revascularization. RESULTS:
      Baseline clinical characteristics, including mean graft age (120 +/- 77 vs. 131
      +/- 86 months, P = 0.14), were similar between groups, save for a higher
      prevalence of systemic hypertension and chronic renal insufficiency, and higher
      body mass index in the diabetic group. Among the 604 SVG lesions treated with
      DES, the angiographic and procedural characteristics were well matched between
      groups except for the higher rate of distal protection device use (32% vs. 29%, P
      = 0.007) in the diabetic group. The rates of 1-year MACE (21% vs. 15%, P = 0.12)
      and all-cause mortality (7.6% vs. 6.7%, P = 0.86) were similar between groups.
      After adjustment for the relevant clinical co-variables, diabetic status was not
      associated with the composite end-point. CONCLUSION: In conclusion, DES, when
      used for the treatment of vein graft lesions, equate the short- and long-term
      outcomes between diabetic and nondiabetic patients, suggesting that DES should be
      considered the default stent in diabetic populations undergoing PCI for the
      treatment of SVG lesions.

PMID- 25059287
TI  - Leaving no hole unclosed: left atrial appendage occlusion in patients having
      closure of patent foramen ovale or atrial septal defect.
AB  - OBJECTIVES: To report procedural outcome of sequential occlusion of the left
      atrial appendage (LAA) and an interatrial septal communication and discuss
      possible indications. BACKGROUND: There are some patients who may have
      indications for both closure of patent foramen ovale (PFO) or atrial septal
      defect (ASD), as well as closure of the LAA. The optimal procedural strategy is
      not known. METHODS: A retrospective review of LAA and PFO/ASD cases at our center
      was performed. Demographic, echocardiographic, and procedural data were recorded.
      RESULTS: Closure of LAA and then PFO/ASD (Group I: 11 patients), closure of both
      in the same setting (Group II: 3 patients), and closure of the PFO/ASD and then
      the LAA (Group III: 3 patients) was performed in a total of 17 patients. Average
      age was 63.5 +/- 9.8 years. Most patients were hypertensive with prior
      cerebrovascular event in 52.9% of patients. Procedural success was 100%.
      Procedural adverse events were 2 episodes of tamponade (in Group I after first
      LAA procedure) treated with pericardiocentesis and 1 access-site hematoma (Group
      II) treated conservatively. CONCLUSIONS: Sequential (staged or during the same
      procedure) closure of the LAA and interatrial communications can be performed
      safely in a carefully selected patient population. This is also the first known
      report of LAA occlusion in patients with prior septal closure devices.

PMID- 25059288
TI  - The impact of intermittent and repetitive cold stress exposure on endoplasmic
      reticulum stress and instability of atherosclerotic plaques.
AB  - BACKGROUND: The incidence of acute coronary syndrome caused by the rupture of
      atherosclerotic plaque and subsequent arterial thrombosis increases as the
      weather gets colder. However, the association between cold stress and
      atherosclerotic plaque rupture is currently unknown. METHODS: An atherosclerotic
      plaque model was established in rabbits by balloon injury and a high-fat diet
      with or without cold stress (4  degrees C, 1 hour per day, 20 weeks) at the onset
      of modeling. Additionally, oxidized low-density lipoprotein (ox-LDL) was applied
      to induce the formation of macrophage foam cells in vitro. RESULTS: Serum lipid
      profiles and inflammatory cytokines (ox-LDL, high-sensitivity C-reactive protein,
      and interleukin-8) were significantly higher in cold stress-exposed rabbits than
      in controls (P<0.05). Animals with atherosclerotic lesions that were exposed to
      cold stress had increased macrophages, foam cells, intima-media thickness, and
      neovascularization in the plaque, along with significantly thinned plaque fibrous
      caps. Moreover, we found that cold stress induced more apoptotic cells in the
      atherosclerotic plaques and up-regulated endoplasmic reticulum stress (ERS)
      associated proteins CHOP, GRP78, and p-JNK (P<0.05). In addition, tunicamycin
      treatment promoted ox-LDL-induced apoptosis, expression of CHOP and GPR78, and
      the p-JNK level in macrophage foam cells, while JNK inhibitor sp600125 reduced
      cell apoptosis and the p-JNK level. The three main ERS sensors sensors
      phosphorylated extracellular signal-regulated kinase (PERK), activating
      transcription factor 6 (ATF6), and inositol-requiring enzyme1 (IRE1) declined
      significantly after ox-LDL treatment. CONCLUSIONS: Cold stress may enhance the
      instability of atherosclerotic plaques through activating ERS and enhancing cell
      apoptosis. Up-regulated CHOP levels mediated by PERK and ATF6 and the activated
      IRE1-XBP1-JNK pathway contributed to the apoptosis of foam cells.

PMID- 25059290
TI  - Correlates and economic outcomes of proton pump inhibitor use by routes in
      intensive care unit patients.
AB  - Objectives were to evaluate correlates, and economic outcomes of proton pump
      inhibitor (PPI) use by route in the intensive care unit from an institutional
      payer perspective. A 13-month retrospective study of electronic medical records
      was conducted of 534 adult (>=19 year-old) intensive care unit patients receiving
      a PPI (39% enteral-only, 34% parenteral-only, 27% both-route) in a Midwest USA
      academic medical center. Possible cost-savings with sensitivity analysis were
      estimated as differences in drug costs (US dollars) between switch eligible
      parenteral and alternate enteral-PPI medication doses. In multivariate logistic
      regression of switch criteria (any oral-medication, orogastric-tube, nothing by
      oral route), significant correlate for enteral versus parenteral PPI-use was any
      oral-medication use but not orogastric-tube. Using enteral
      esomeprazole/lansoprazole instead of parenteral (esomeprazole/pantoprazole) PPI
      (in 37% i.e. 696 of 1895 switch-eligible doses) would have saved US$2384.17 or
      US$3564.86, respectively. By switching eligible patients on oral-medications or
      on orogastric-tube from parenteral- to enteral-PPI, institutions can realize
      significant drug cost-savings. 

PMID- 25059289
TI  - Transforming growth factor-beta1 reduces apoptosis via autophagy activation in
      hepatic stellate cells.
AB  - Autophagy is a metabolic process that is important in fibrogenesis, in which
      cellular components are degraded by lysosomal machinery. Transforming growth
      factor beta1 (TGF-beta1) is a potent fibrogenic cytokine involved in liver
      fibrosis; however, it remains elusive whether autophagy is regulated by TGF-beta1
      in this process. In the present study, the function of TGF-beta1-mediated
      autophagy in the proliferation and apoptosis of hepatic stellate cells (HSCs) was
      investigated. A rat HSC cell line (HSC-T6) was incubated with or without TGF
      beta1 followed by bafilomycin A1, and microtubule-associated proteins 1A/1B light
      chain 3 (LC3) small interfering (si)RNA was used to inhibit autophagy in order to
      assess the association between TGF-beta1 and autophagy. HSC-T6 cell transient
      transfection was accomplished with a pLVX-AcGFP-N1-rLC3B-encoding plasmid. An MTS
      assay and flow cytometry were utilized to detect proliferation and apoptosis of
      HSC-T6 cells. Quantitative polymerase chain reaction, immunofluorescence and
      western blot analysis were used to detect the presence of activation markers.
      Proliferation was increased and apoptosis was reduced in HSC-T6 cells treated
      with TGF-beta1 compared with cells subjected to serum deprivation. However, when
      HSC-T6 cells were treated with bafilomycin A1 and LC3 siRNA, increased apoptosis
      and reduced proliferation were observed. In addition, protein and mRNA expression
      levels of the autophagy marker LC3 were significantly increased. GFP-LC3 punctate
      markings were more prolific following TGF-beta1 treatment of HSC-T6 cells,
      indicating that TGF-beta1 may rescue HSC-T6 cells from serum deprivation and
      reduce apoptosis via autophagy induction. The present study elucidated the
      possible functions of TGF-beta1-mediated autophagy in the pathological process of
      liver fibrosis.

PMID- 25059291
TI  - Live eyeworm (Oxyspirura petrowi) extraction, in vitro culture, and transfer for
      experimental studies.
AB  - Northern bobwhite ( Colinus virginianus ) have experienced a dramatic decline in
      West Texas over the last 3 yr, and investigations are underway to evaluate the
      role of parasites in this decline. One of the key parasites being investigated is
      the eyeworm (Oxyspirura petrowi). Live eyeworms were extracted from both live and
      dead northern bobwhites, and in vitro survival was tested using 10 liquid media.
      Eyeworms placed in an egg white and physiological saline solution lived for at
      least 36 days. Live O. petrowi placed into the eyes of uninfected pen-raised
      bobwhites were monitored for 21 days to demonstrate successful transfer. Eyeworm
      behavior during feeding, mating, and development were monitored. This study is
      important to research that requires "banking" of live O. petrowi from wild
      captured definitive hosts for life history studies and assessing the impact of O.
      petrowi on host individuals. 

PMID- 25059292
TI  - Beyond Cassie equation: local structure of heterogeneous surfaces determines the
      contact angles of microdroplets.
AB  - The application of Cassie equation to microscopic droplets is recently under
      intense debate because the microdroplet dimension is often of the same order of
      magnitude as the characteristic size of substrate heterogeneities, and the
      mechanism to describe the contact angle of microdroplets is not clear. By
      representing real surfaces statistically as an ensemble of patterned surfaces
      with randomly or regularly distributed heterogeneities (patches), lattice
      Boltzmann simulations here show that the contact angle of microdroplets has a
      wide distribution, either continuous or discrete, depending on the patch size.
      The origin of multiple contact angles observed is ascribed to the contact line
      pinning effect induced by substrate heterogeneities. We demonstrate that the
      local feature of substrate structure near the contact line determines the range
      of contact angles that can be stabilized, while the certain contact angle
      observed is closely related to the contact line width. 

PMID- 25059293
TI  - Peer Review: Publication's Gold Standard.

PMID- 25059294
TI  - Chickadees with bigger brains have smaller digestive tracts: a multipopulation
      comparison.
AB  - The factors leading to the evolution of large brain size remain controversial.
      Brains are metabolically expensive and larger brains demand higher maintenance
      costs. The expensive-tissue hypothesis suggests that when selection favors larger
      brains, evolutionary changes in brain size can occur without an overall increase
      in energetic costs when brain size represents a trade-off with the size of other
      expensive tissues, such as the digestive tract. Still, support for this
      hypothesis is equivocal. We compared mean brain mass, digestive tract mass
      (stomach and gut) and heart mass in 9 populations of black-capped chickadees
      along a gradient of winter climate severity. Mean brain mass and telencephalon
      volume showed significant population variation with larger brains associated with
      harsher winter conditions. Mean population brain mass and telencephalon volume
      were also negatively related to both stomach and gut mass. Mean population heart
      mass, on the other hand, was not significantly associated with either mean brain
      mass or winter climate severity. Mean brain mass was negatively associated with
      body mass, with chickadees from harsher environments being smaller but having
      larger brains and smaller digestive tracts. Our results are consistent with the
      expensive-tissue hypothesis, and suggest that a harsher winter climate might
      favor larger brains, which might be associated with a reduction in size of the
      digestive tract. These findings could potentially be a result of population
      differences in the winter climate diet related to the perishability of more
      efficient invertebrate-based food caches.

PMID- 25059295
TI  - Proteomic analysis of barley cell nuclei purified by flow sorting.
AB  - Many proteins are present in the nucleus; some are involved with its structural
      and functional organization, some with gene expression, and some with cell
      division. The plant nuclear proteome has not been well explored. Its
      characterization requires extraction methods which minimize both the artifactual
      alteration of the proteins and the extent of contamination with non-nuclear
      proteins. The conventional multi-step fractionation procedure is both laborious
      and prone to contamination. Here, we describe a single-step method based on flow
      sorting. The method allows the separation of G1, S and G2 phase nuclei and
      minimizes the risk of contamination by non-nuclear proteins. Preliminary results
      obtained using G1 phase cell nuclei from barley root tips indicate that flow
      sorting coupled with a protein/peptide separation and mass spectrometry will
      permit a comprehensive characterization of the plant nuclear proteome.

PMID- 25059296
TI  - Do therapists address gender and power in infidelity? A feminist analysis of the
      treatment literature.
AB  - Sociocontextual factors such as gender and power play an important role in the
      etiology of affairs and in recovery from them, yet it is unclear how current
      treatment models address these issues. Drawing on feminist epistemology, this
      study utilized a grounded theory analysis of 29 scholarly articles and books on
      infidelity treatment published between 2000 and 2010 to identify the
      circumstances under which gender and power issues were or were not part of
      treatment. We found five conditions that limit attention to gender and power: (a)
      speaking (or assuming) as though partners are equal, (b) reframing infidelity as
      a relationship problem, (c) limiting discussion of societal context to
      background, (d) not considering how societal gender and power patterns impact
      relationship dynamics, and (e) limiting discussion of ethics on how to position
      around infidelity. Analysis explored how each occurred across three phases of
      couple therapy. The findings provide a useful foundation for a sociocontextual
      framework for infidelity treatment.

PMID- 25059297
TI  - Toward mutual support: a task analysis of the relational justice approach to
      infidelity.
AB  - Gender, culture, and power issues are intrinsic to the etiology of infidelity,
      but the clinical literature offers little guidance on how to work with these
      concerns. The Relational Justice Approach (RJA) to infidelity (Williams, Family
      Process, 2011, 50, 516) uniquely places gender and power issues at the heart of
      clinical change; however, this approach has not been systematically studied.
      Therefore a qualitative task analysis was utilized to understand how change
      occurs in RJA. The findings indicated four necessary tasks: (a) creating an
      equitable foundation for healing, (b) creating space for alternate gender
      discourse, (c) pursuing relational responsibility of powerful partner, and (d)
      new experience of mutual support. Therapists' attention to power dynamics that
      organize couple relationships, leadership in intervening in power processes, and
      socio-cultural attunement to gender discourses were foundational to this work.
      These findings help clarify the processes by which mutual healing from the trauma
      of infidelity may occur and offer empirically based actions that therapists can
      take to facilitate mutual support.

PMID- 25059298
TI  - Enactments in emotionally focused couple therapy: shaping moments of contact and
      change.
AB  - Emotionally focused couple therapy (EFT) uses enactments to shape responsive
      attachment-significant contact and to change couple interaction. In this article,
      we show how EFT enactments differ from enactments in other therapy approaches,
      present a theory of EFT enactments, a model for creating EFT enactments, and an
      extended case example of an EFT enactment. 

PMID- 25059299
TI  - The Self Assessment of Future Events Scale (SAFE): assessing perceptions of risk
      for future violence in intimate partner relationships.
AB  - The purpose of this study was to develop a survey measure, appropriate for use in
      clinical or research settings, to assess respondent's perceptions that their
      partner will engage in future physical violence, verbal/psychological violence,
      or controlling behaviors. Data were collected from adults in intimate
      relationships. Exploratory factor analysis was used to refine the measure and
      confirmatory factor analysis provided evidence for the fit of the final version
      of the measure. Scores on the measure indicated less safety for participants in
      distressed relationships and for participants meeting the study criteria for
      PTSD. Scores on the measure also indicated significantly decreased safety for
      participants that reported being the victims of physical violence and
      participants reporting both victimization and perpetration in their current
      intimate relationships.

PMID- 25059300
TI  - Trying to comfort the parent: a qualitative study of children dealing with
      parental depression.
AB  - In this article, we look at children's experiences of parentification in families
      in which one of the parents is hospitalized for depression. Children (7-14 years
      old) and their parents were invited for a family interview. Using thematic
      analysis, we constructed a general framework of 14 children's experiences, guided
      by the explorative research question: How do children experience parental
      depression and how do they experience their own caregiving in the family? The
      thematic analysis revealed eight themes. One of these themes (trying to comfort
      the parent) was selected for a microanalysis in one family interview. Our study
      illustrates the process of overt negotiating of caretaking between parent and
      child with an underlying moral dilemma and related emotions. The dynamic of
      children hiding their worry can be seen as an answer to the parent's expressed
      wish to not burden her children. These dynamics are situated in ongoing debates
      in family therapy literature, and some suggestions for therapeutic practice are
      formulated.

PMID- 25059301
TI  - The impact of the within my reach relationship training on relationship skills
      and outcomes for low-income individuals.
AB  - A federal grant was awarded to provide the Within My Reach healthy relationships
      curriculum to low-income, at-risk individuals involved with various social
      service agencies. The effectiveness of this curriculum was evaluated for 202
      participants through measures of training and relationship outcomes pre-,
      immediately post- and 6 months posttraining. Participants experienced high levels
      of training satisfaction; significant increases in knowledge,
      communication/conflict resolution skills, and relationship quality; as well as a
      trend in the reduction of relationship violence. An important implication of this
      research is that MFTs may broaden their service delivery to at-risk individuals
      by collaborating with community agencies to adapt established relationship
      enhancement programs, evidence-based tools, and principles that complement
      traditional couples therapy. 

PMID- 25059302
TI  - Female adoptees' experiences balancing relationships with biological and adoptive
      mothers post-reunification.
AB  - Using a feminist postmodern perspective and the sensitizing concept of split
      loyalties from Contextual Theory, the primary purpose of this qualitative study
      was to develop a better understanding of how adult female adoptees from closed
      adoptions negotiate relationships with their adoptive and biological mothers post
      reunion. We conducted semi-structured individual interviews with nine adult
      female adoptees, ages 28-52, who were adopted prior to the age of two. Six were
      Caucasian, three were African American, and the average age at reunion was 29.
      Grounded theory techniques were used to code the qualitative data, in particular
      the constant comparative method of analysis. Four main categories emerged: (a)
      Negotiating Mother-Daughter Relationships, (b) Relating to Mothers Equitably, (c)
      Loyalty, and (d) Adoptees' Emotional Needs. Our findings suggest the adoptive
      mother-daughter relationship has a salient effect on adoptees' relationships with
      biological mothers post-reunion. Loyalty to the adoptive mother seems to
      influence the evolving relationship and closeness displayed toward the birth
      mother. Adult female adoptees from closed adoptions described struggling with
      managing their two mother-daughter relationships and need clinical help
      addressing their own emotional needs.

PMID- 25059303
TI  - Core competencies in social constructionist supervision?
AB  - Family therapy is moving increasingly toward evidence-based practice and
      competency-based training. This article explores what might seem to be an
      unlikely link between social constructionist supervision, which is based on
      dialogic and fluid processes of meaning-making, and the increasing reliance on
      discrete core competencies in the education and training of family therapists. We
      propose an alternate approach to competencies for supervision with therapists in
      training that, among other things, invites accountability and provides evaluative
      props. The approach we propose is based on a set of orientations that we hope
      reflect the dialogic and contextual nature of social constructionist practice and
      supervision. These orientations consist of reflexivity and attention to power,
      fostering polyphony and generativity, collaborative stance, and focus on client
      resourcefulness. Ideas and questions for supervisors and therapists in training
      to address the orientations are articulated.

PMID- 25059304
TI  - The lived experience of family members of persons who compulsively hoard: a
      qualitative study.
AB  - The current study took an Interpretive Phenomenological Analysis approach to
      investigate the lived experiences of 12 family members of persons who hoard to
      better understand family members' cognitions, emotions, perceptions, experiences,
      and responses in their interactions with their loved ones who hoard. Five
      overarching themes for the participants' experiences of having a person who
      hoards in the family emerged: negative feelings toward the persons who hoard;
      lack of understanding of hoarding behavior; experiences of loss; internal
      barriers to seeking support; and internal conflicts. Clinical implications and
      recommendations for future research are discussed, including a proposed
      application of an ambiguous loss framework for understanding and working with the
      experiences of family members of persons who hoard.

PMID- 25059307
TI  - Effects of adverse early-life events on aggression and anti-social behaviours in
      animals and humans.
AB  - We review the impact of early adversities on the development of violence and
      antisocial behaviour in humans, and present three aetiological animal models of
      escalated rodent aggression, each disentangling the consequences of one
      particular adverse early-life factor. A review of the human data, as well as
      those obtained with the animal models of repeated maternal separation, post
      weaning social isolation and peripubertal stress, clearly shows that adverse
      developmental conditions strongly affect aggressive behaviour displayed in
      adulthood, the emotional responses to social challenges and the neuronal
      mechanisms activated by conflict. Although similarities between models are
      evident, important differences were also noted, demonstrating that the
      behavioural, emotional and neuronal consequences of early adversities are to a
      large extent dependent on aetiological factors. These findings support recent
      theories on human aggression, which suggest that particular developmental
      trajectories lead to specific forms of aggressive behaviour and brain
      dysfunctions. However, dissecting the roles of particular aetiological factors in
      humans is difficult because these occur in various combinations; in addition, the
      neuroscientific tools employed in humans still lack the depth of analysis of
      those used in animal research. We suggest that the analytical approach of the
      rodent models presented here may be successfully used to complement human
      findings and to develop integrative models of the complex relationship between
      early adversity, brain development and aggressive behaviour. 

PMID- 25059308
TI  - Pharmacoeconomic implications of lenalidomide maintenance therapy in multiple
      myeloma.
AB  - We compared the three arms of the MM-015 randomized phase III clinical trial
      [melphalan and prednisone (MP), MP plus lenalidomide (MPR), and MPR plus
      lenalidomide maintenance (MPR-R)] to determine whether the addition of
      lenalidomide maintenance therapy for primary treatment of multiple myeloma is
      cost-effective. We used progression-free survival and adverse event data from the
      MM-015 study for the analysis. Two novel measures of cost-effectiveness termed
      the Average Cumulative Cost per Patient (ACCP) and the Average Cumulative Cost
      per Progression-Free Survivor (ACCPFS) were developed for the purpose of this
      analysis. The ACCP of MP was USD 18,218, compared to USD 167,862 for MPR and USD
      309,173 for MPR-R. The ACCPFS was highest with MPR at USD 1,555,443, while MP was
      USD 313,592 and MPR-R was USD 690,111. MPR-R is superior to MPR in terms of
      preventing the first progression after initial therapy. However, the addition of
      lenalidomide to MP in the induction and also in the maintenance setting leads to
      significant costs.

PMID- 25059309
TI  - Fractionation of carboxylated carbon nanotubes and the corresponding variation in
      their colloidal behavior.
AB  - Length dependent dispersibility of carboxylated multi-walled carbon nanotubes is
      presented using a novel approach where a batch of carboxylated nanotubes was size
      sorted via ultracentrifugation into different fractions with lengths ranging from
      150 to 950 nm. The different fractions had the same tube diameter and degree of
      oxidation. The dispersibility of the nanotube fractions showed dependence on the
      length where the longer tubes showed more aggregation in terms of larger particle
      size, zeta potential and lower critical coagulation concentrations (CCC) in the
      presence of electrolytes. It is hypothesized that the longer tubes formed a more
      complex electrostatic double layer that increased their entanglement and
      aggregation. 

PMID- 25059312
TI  - Nonlinear Flow Process: A New Package to Compute Nonlinear Flow in MODFLOW.
AB  - A new MODFLOW package (Nonlinear Flow Process; NLFP) simulating nonlinear flow
      following the Forchheimer equation was developed and implemented in MODLFOW-2005.
      The method is based on an iterative modification of the conductance calculated
      and used by MODFLOW to obtain an effective Forchheimer conductance. The package
      is compatible with the different layer types, boundary conditions, and solvers as
      well as the wetting capability of MODFLOW. The correct implementation is
      demonstrated using four different benchmark scenarios for which analytical
      solutions are available. A scenario considering transient flow in a more
      realistic setting and a larger model domain with a higher number of cells
      demonstrates that NLFP performs well under more complex conditions, although it
      converges moderately slower than the standard MODFLOW depending on the
      nonlinearity of flow. Thus, this new tool opens a field of opportunities to
      groundwater flow simulation with MODFLOW, especially for core sample simulation
      or vuggy karstified aquifers as well as for nonlinear flow in the vicinity of
      pumping wells. 

PMID- 25059313
TI  - Work economic sectors and cardiovascular risk factors: cross-sectional analysis
      based on the RECORD Study.
AB  - BACKGROUND: Little is known on the comparative effect of work economic sectors on
      multiple cardiovascular risk factors. Such information may be useful to target
      Public health interventions, e.g., through the occupational medicine. We
      investigated whether and how a large panel of cardiovascular risk factors varied
      between 11 work economic sectors. METHODS: Data on 4360 participants from the
      French RECORD Study geolocated at their residence were analyzed. Ten outcomes
      were assessed: body mass index (BMI), waist circumference, systolic and diastolic
      blood pressure (BP), pulse pressure, total cholesterol, glycaemia, high-density
      lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and
      resting heart rate. Multilevel linear regression models stratified by sex and
      adjusted for individual and neighborhood sociodemographic characteristics were
      estimated. RESULTS: Among men, the Health and social work sector was found to be
      the most protective sector for BMI, waist circumference, and glycaemia (while the
      Construction sector and the Transport and communications sector tended to be
      unfavorable for these outcomes). The Health and social work sector was also
      associated with higher HDL cholesterol among men. However, men working in the
      Health and social work sector showed the highest systolic BP and pulse pressure.
      Women working in the Health and social work sector had the highest BMI, the
      largest waist circumference, and the most elevated systolic and diastolic BP. The
      Commercial and repair of vehicles sector, the Transport and communication sector,
      and the Collective, social, and personal services sector were associated with a
      more favorable profile for these risk factors among women. CONCLUSION: Work
      economic sectors contribute to shape metabolic and cardiovascular parameters
      after adjustment for individual/neighborhood sociodemographic characteristics.
      However, patterns of associations varied strikingly according to the risk factor
      examined and between men and women. Such findings may be useful to target
      interventions for reducing cardiovascular risk, e.g., through the occupational
      medicine.

PMID- 25059314
TI  - Undertreatment of erectile dysfunction: claims analysis of 6.2 million patients.
AB  - INTRODUCTION: Prior research conducted on treatment of erectile dysfunction (ED)
      has been derived from surveys involving relatively small populations of men.
      There are needs for large population-based studies in this area. Our study
      addresses that need. AIM: The aim of this study was to characterize ED treatment
      among a large population of men. METHODS: Patients >=30 years in commercial
      insurance dataset with diagnosis code for ED during 12-month period ending June
      2011 were identified. Men were considered "treated" if prescription was filled
      for phosphodiesterase type 5 inhibitor (PDE5i), injection or urethral
      prostaglandins, or androgen replacement (ART) during study period. "Untreated"
      patients received the diagnosis but did not fill prescription. Statistical
      analyses were used to compare prescription frequency with clinical
      characteristics, including age and comorbidities. MAIN OUTCOME MEASURES: ED
      treatment rates among large population of insured men, treatment types employed,
      patient demographics, associated medical comorbidities of this population, and
      prescriber details were the main outcome measures. RESULTS: Only 25.4% of
      6,228,509 men with ED were treated during study period. While PDE5is were the
      most commonly prescribed medical therapy (75.2%), ART was utilized as monotherapy
      or in combination therapy in 30.6% of men. ART was significantly (P < 0.0001)
      more frequently used in men <40 and >65 years. Although ED frequency was
      associated with increased age and number of comorbidities, men >60 years were
      significantly (P < 0.0001) less likely to be treated compared with men aged 40-59
      years. Additionally, treatment frequency did not vary as a function of number of
      comorbidities. However, compared with men with prostate cancer, men with comorbid
      hypogonadism, sleep disorders, benign prostatic hyperplasia, or components of
      metabolic syndrome were (P < 0.0001) more likely to be treated. CONCLUSIONS:
      Despite high prevalence of ED with age and comorbidities, most men continue
      receiving no treatment. Although benefits of medical intervention for ED are well
      recognized, many barriers to treatment continually exist including physician,
      patient and partner preference and knowledge.

PMID- 25059315
TI  - Using database reports to reduce workplace violence: Perceptions of hospital
      stakeholders.
AB  - BACKGROUND: Documented incidents of violence provide the foundation for any
      workplace violence prevention program. However, no published research to date has
      examined stakeholders' preferences for workplace violence data reports in
      healthcare settings. If relevant data are not readily available and effectively
      summarized and presented, the likelihood is low that they will be utilized by
      stakeholders in targeted efforts to reduce violence. OBJECTIVE: To discover and
      describe hospital system stakeholders' perceptions of database-generated
      workplace violence data reports. PARTICIPANTS: Eight hospital system stakeholders
      representing Human Resources, Security, Occupational Health Services, Quality and
      Safety, and Labor in a large, metropolitan hospital system. METHODS: The hospital
      system utilizes a central database for reporting adverse workplace events,
      including incidents of violence. A focus group was conducted to identify
      stakeholders' preferences and specifications for standardized, computerized
      reports of workplace violence data to be generated by the central database. The
      discussion was audio-taped, transcribed verbatim, processed as text, and analyzed
      using stepwise content analysis. RESULTS: Five distinct themes emerged from
      participant responses: Concerns, Etiology, Customization, Use, and Outcomes. In
      general, stakeholders wanted data reports to provide ''the big picture,'' i.e.,
      rates of occurrence; reasons for and details regarding incident occurrence;
      consequences for the individual employee and/or the workplace; and organizational
      efforts that were employed to deal with the incident. CONCLUSIONS: Exploring
      stakeholder views regarding workplace violence summary reports provided concrete
      information on the preferred content, format, and use of workplace violence data.
      Participants desired both epidemiological and incident-specific data in order to
      better understand and work to prevent the workplace violence occurring in their
      hospital system.

PMID- 25059316
TI  - Premature aging induced by radiation exhibits pro-atherosclerotic effects
      mediated by epigenetic activation of CD44 expression.
AB  - Age is undoubtedly a major risk factor for heart disease. However, the reason for
      this is not entirely clear. In the course of our investigation into the mechanism
      of radiation-induced cardiovascular disease, we made several unexpected findings
      that inform us on this question. We observed that human coronary endothelial
      cells, while being able to initiate repair of radiation-induced DNA damage, often
      fail to complete the repair and become senescent. Such radiation-induced cellular
      aging occurs through a mutation-independent route. Endothelial cells that aged
      naturally through replication or as a result of radiation exhibited
      indistinguishable characteristics. The promoter regions of the CD44 gene in aging
      endothelial cells become demethylated, and the proteins are highly expressed on
      the cell surface, making the cells adhesive for monocytes. Adhesion is a cardinal
      feature that recruits monocytes to the endothelium, allowing them to infiltrate
      the vessel wall and initiate atherosclerosis. The epigenetic activation of CD44
      expression is particularly significant as it causes persistent elevated CD44
      protein expression, making senescent endothelial cells chronically adhesive. In
      addition to understanding why cardiovascular disease increases with age, these
      observations provide insights into the puzzling association between radiation and
      cardiovascular disease and highlight the need to consider premature aging as an
      additional risk of radiation to human health. 

PMID- 25059317
TI  - Morphological features and length measurements of fetal lateral ventricles at 16
      25 weeks of gestation by magnetic resonance imaging.
AB  - Normal growth of the lateral ventricles (LVs) was characterized three
      dimensionally using magnetic resonance imaging (MRI) data from 16 human fetuses
      at 16-25 weeks of gestation. The LV was differentiated into four primary regions,
      the anterior horn, central parts, posterior horn, and inferior horn, at 16 weeks
      of gestation. The LV changed shape mainly by elongation and narrowing, which
      corresponded to the external and internal growth of the surrounding cerebrum. Six
      length parameters measured in the LV correlated with biparietal diameter by
      simple regression analysis (R(2) range, 0.56-0.93), which may be valuable for
      establishing a standardized prenatal protocol to assess fetal well-being and
      development across intrauterine periods. No correlation was found between
      biparietal diameter and LV volume (R(2) = 0.13).

PMID- 25059318
TI  - Health and disease: exploring the relation between parasitic infections, child
      nutrition status, and markets.
AB  - Research in bioarchaeology and among living people provides insight into the
      biological and biocultural consequences of subsistence, political, and economic
      transitions. Central to this effort is examining infectious disease, such as
      diarrheal disease, respiratory infections, and parasitic infections because they
      are an important source of nutritional and energetic stress in both past and
      current groups. Although infection may not always result in overt disease,
      frequent exposure results in biological stress with a negative effect on child
      growth and, by extension, health. The goal of this article is to examine the
      association between a common class of infectious disease, soil-transmitted
      helminth worms, and nutritional status among youth living in communities that
      vary with respect to their distance from a commercial center. In 2007,
      anthropometric measurements and parasitological surveys were collected for 338 2
      14-year-old children and adolescents living in lowland Bolivia as part of the
      Tsimane' Amazonian Panel Study. Associations between the presence of helminth
      infections and markers of both short- and long-term nutritional status were
      overall weak. Youth living in communities distant from the commercial center were
      more likely to be positive for multiple parasite species than youth in near
      communities, but youth in mid-distance communities had lower infection rates.
      This article demonstrates the challenge of identifying associations between
      nutritional and disease stress when individual and household factors are nested
      in a larger context of socioeconomic and environmental change. Increased
      collaboration between bioarchaeology and human biology should continue to examine
      the connections between stress and disease across time.

PMID- 25059319
TI  - Phase I dose-escalation study of the HSP90 inhibitor AUY922 in Japanese patients
      with advanced solid tumors.
AB  - PURPOSE: AUY922 is a potent non-geldanamycin inhibitor of heat-shock protein 90.
      This study was carried out in Japanese patients to determine the maximum
      tolerated dose (MTD), and to characterize safety, tolerability and
      pharmacokinetics of single-agent AUY922. METHODS: Japanese patients with advanced
      solid tumors whose disease had progressed on at least one line of standard
      therapy, or for whom no standard therapy existed, were treated with AUY922
      (intravenous, once-weekly, 28-day cycle, starting dose 8 mg/m(2)). RESULTS:
      Thirty-one patients were treated. Two DLTs were reported in one patient of the 54
      mg/m(2) cohort; fatigue and decreased appetite (both Grade 3, resolving to Grade
      1 within 8 days). No MTD was determined, and the dose recommended for Phase II
      studies was determined to be 70 mg/m(2) once-weekly. Most common drug-related
      toxicities were diarrhea, night blindness and nausea. Grade 1 and 2 visual
      toxicities at high AUY922 doses >=22 mg/m(2) were observed. Ten patients (32 %)
      achieved a best overall response of stable disease, and one patient (3 %)
      achieved a confirmed partial response. CONCLUSION: Overall, AUY922 exhibited
      acceptable toxicities and demonstrated potential clinical activity in Japanese
      patients, with similar safety and pharmacokinetic profiles to those reported in a
      preceding global Phase I study in Western patients (CAUY922A2101).

PMID- 25059320
TI  - Long progression-free survival with first-line paclitaxel plus platinum is
      associated with improved response and progression-free survival with second-line
      docetaxel in advanced non-small-cell lung cancer.
AB  - PURPOSE: Paclitaxel and docetaxel are two taxanes approved for the treatment of
      non-small-cell lung cancer (NSCLC). However, there is limited evidence regarding
      the efficacy of docetaxel in NSCLC previously treated with a paclitaxel-platinum
      doublet (PP). The aim of our study was to evaluate the response to docetaxel in
      NSCLC patients with prior PP treatment. METHODS: Patients with stage IV NSCLC
      treated with PP that presented disease progression and received docetaxel as
      second-line treatment were included. Demographics, clinical characteristics, EGFR
      mutation status, objective response (OR), overall survival (OS), progression-free
      survival (PFS), and PFS without chemotherapy after first line with PP were
      analyzed. RESULTS: Sixty-three patients were evaluated. Median age was 58 years,
      54% of patients were women, 53% were never-smokers, and 39% had EGFR mutations.
      OR and median PFS for PP were 36.5% and 6.7 months, respectively. OR and median
      PFS for docetaxel were 19% and 3.8 months, respectively. Patients with EGFR
      mutations had better response to docetaxel compared with wild-type patients (26
      vs. 17%, p = 0.028). However, only long PFS (>6 months) to first-line PP was
      independently associated with a higher OR [RR 6.3, 95% CI (1.03-38.4), p =
      0.046], and longer PFS [0.49 (0.25-0.9)] and OS [0.2 (0.06-0.7), p = 0.008] to
      second-line docetaxel compared with patients with short PFS (<=6 months) to PP.
      CONCLUSIONS: Previous use of PP does not preclude a favorable response to
      docetaxel in NSCLC. Long PFS with PP may help select NSCLC patients who benefit
      from second-line docetaxel.

PMID- 25059322
TI  - Protein Systems Biology: Method, Regulation, and Networks.

PMID- 25059321
TI  - The impact of individual and organisational factors on engagement of individuals
      with intellectual disability living in community group homes: a multilevel model.
AB  - BACKGROUND: Being engaged in daily activities is a strong indicator of quality of
      life for individuals with intellectual disability (ID) who live in small
      community group homes. This study aimed to identify individual and organisational
      factors that predict high levels of engagement. METHOD: Individuals with ID (n =
      78), direct support professionals (DSPs; n = 174) and supervisors (n = 21) from
      21 US group homes participated in the study. For each individual with ID, we
      conducted 80 min of observation at the person's residence. Information was also
      gathered regarding demographic characteristics, DSP competence, supervisor years
      of experience and management practices. Data were analysed using multilevel
      modelling. RESULTS: On average, individuals were engaged in social activities 12%
      of observed time and non-social activities 35% of the time. Individuals with
      greater adaptive skills who were supported by more competent staff showed
      significantly higher levels of social engagement. Individuals with less severe
      deficits in adaptive behaviours and less challenging behaviour showed higher
      levels of non-social engagement. Although none of the factors related to group
      homes were significant, 24% of the variance in non-social engagement existed
      among group homes. CONCLUSION: These results suggested that engagement is a
      dynamic construct. The extent to which an individual with ID is engaged in daily
      life is a result of interplay between the individual's characteristics and the
      group home environment. Future research is needed to investigate the influence of
      variables specific to the group home on the engagement level of individuals with
      disabilities.

PMID- 25059323
TI  - Identifying protein-protein binding sites with a combined energy function.
AB  - Determination of binding sites between proteins is widely applied in many fields,
      such as drug design and the structural and functional analysis. The protein
      protein binding sites can be formed by two subunits in a complex. Understanding
      energetics and mechanisms of complexes remains one of the essential problems in
      binding site prediction. We develop a system, P-Binder, for identifying binding
      sites based on shape complementarity, side-chain conformations and interacting
      amino acid information. P-Binder utilizes an enumeration method to generate all
      possible configurations between two proteins, and uses a side-chain packing
      program to identify the bound states. The system reports the binding sites with
      the highest ranked configurations, evaluated through a linear combination of four
      statistical energy items. The experiments show that our method performs better
      than other prediction methods. A comparison with some existing approaches shows P
      Binder to improve the success rate by at least 12.3%. We test P-Binder on 176
      protein-protein complexes in Benchmark v4.0. The overall values of accuracy and
      coverage are 63.8% and 68.8% for the bound state, and 51.0% and 60.9% for the
      unbound state. 

PMID- 25059324
TI  - Predicting protein functions by using unbalanced bi-random walk algorithm on
      protein-protein interaction network and functional interrelationship network.
AB  - Accurate annotation of protein functions is still a big challenge for
      understanding life in the post-genomic era. Recently, some methods have been
      developed to solve the problem by incorporating functional similarity of GO terms
      into protein-protein interaction (PPI) network, which are based on the
      observation that a protein tends to share some common functions with proteins
      that interact with it in PPI network, and two similar GO terms in functional
      interrelationship network usually co-annotate some common proteins. However,
      these methods annotate functions of proteins by considering at the same level
      neighbors of proteins and GO terms respectively, and few attempts have been made
      to investigate their difference. Given the topological and structural difference
      between PPI network and functional interrelationship network, we firstly
      investigate at which level neighbors of proteins tend to have functional
      associations and at which level neighbors of GO terms usually co-annotate some
      common proteins. Then, an unbalanced Bi-random walk (UBiRW) algorithm which
      iteratively walks different number of steps in the two networks is adopted to
      find protein-GO term associations according to some known associations.
      Experiments are carried out on S. cerevisiae data. The results show that our
      method achieves better prediction performance not only than methods that only use
      PPI network data, but also than methods that consider at the same level neighbors
      of proteins and of GO terms. 

PMID- 25059325
TI  - The organelle-focused proteomes and interactomes in rice.
AB  - Protein subcellular localization has been a long-standing key problem in
      investigating proteins' function, which provides important clues for revealing
      their functions and aids in understanding their interactions with other
      biomolecules at the cellular level. Here, we systematically defined the organelle
      focused proteomes and interactomes in Oryza sativa. A total of 83.42% of the
      whole rice proteome obtained their subcellular localizations based on manual
      annotation, manual adjustment and predictors' cross validation. The final
      organelle-focused interactomes were located in nine organelles. Furthermore, we
      discussed the cross talk bias between different organelles and the function
      organization accounting for nine organelles. Motif analysis illustrated the
      protein interaction bias in different organelles to implement certain biology
      functions. We exemplified the connection between functions and the
      overrepresented motifs in the organelle-focused interactomes and exemplified how
      to infer the functions of unknown proteins via expanding the overrepresented
      motifs. 

PMID- 25059326
TI  - Evaluating protein-protein interaction (PPI) networks for diseases pathway,
      target discovery, and drug-design using 'in silico pharmacology'.
AB  - In silico pharmacology is a promising field in the current state-of drug
      discovery. This area exploits "protein-protein Interaction (PPI) network analysis
      for drug discovery using the drug "target class". To document the current status,
      we have discussed in this article how this an integrated system of PPI networks
      contribute to understand the disease pathways, present state-of-the-art drug
      target discovery and drug discovery process. This review article enhances our
      knowledge on conventional drug discovery and current drug discovery using in
      silico techniques, best "target class", universal architecture of PPI networks,
      the present scenario of disease pathways and protein-protein interaction networks
      as well as the method to comprehend the PPI networks. Taken all together,
      ultimately a snapshot has been discussed to be familiar with how PPI network
      architecture can used to validate a drug target. At the conclusion, we have
      illustrated the future directions of PPI in target discovery and drug-design.

PMID- 25059327
TI  - Crucial enzymes in the hydroxylated triacylglycerol-ricinoleate biosynthesis
      pathway of castor bean.
AB  - Castor bean (Ricinus communis L.) is an important oilseed crop for the rich
      hydroxylated triacylglycerol (TAG)-ricinoleate which is a raw material with wide
      applications in industry. Hydroxylated TAG synthesis occurs through complicated
      pathways among multiple subcellular organelles. Some crucial enzymes have been
      identified in previous studies. After analyzing the available castor tissue
      specific transcriptome sequencing data and comparing the classic pathways in
      other plants, a possible de novo biosynthesis pathway for the hydroxylated TAG
      has been revealed. In this study, some other crucial enzymes were ascertained and
      their expression levels were characterized and pinpointed into the pathways in
      castor. Several key enzymes were analyzed in terms of structure, biofunction
      prediction and similarity of expression pattern mechanisms, aiming to give an
      insight on the better understandings of the molecular knowledge for this oil-rich
      plant and the crucial enzyme performances in the hydroxylated triacylglycerol
      ricinoleate biosynthesis pathways. 

PMID- 25059328
TI  - Amino acid network for the discrimination of native protein structures from
      decoys.
AB  - With the development of structural genomics projects, the discrimination of
      native proteins from decoys has become one of the major challenges in protein
      structure prediction. In comparison with the energy function based techniques,
      amino acid network provides a simple but efficient method for the native
      structure selection. Amino acid network (AAN) is a graph representation of
      protein structure where amino acids in the protein are the nodes and their
      interactions or contacts are the edges. In this review, we first briefly
      summarized the methods for the construction and characterization of AANs. Then
      the four network properties, i.e. average degree, complexity, clustering
      coefficient of the largest cluster (CCoe) and the size of the top large
      communities (CComS), applied to the native structure selection are discussed and
      summarized. We concluded with the discussion of the future perspective on the
      application of AAN for the native folding detecting among the decoy sets. 

PMID- 25059329
TI  - Prediction of protein-protein interactions based on protein-protein correlation
      using least squares regression.
AB  - In order to transform protein sequences into the feature vectors, several works
      have been done, such as computing auto covariance (AC), conjoint triad (CT),
      local descriptor (LD), moran autocorrelation (MA), normalized moreaubroto
      autocorrelation (NMB) and so on. In this paper, we shall adopt these
      transformation methods to encode the proteins, respectively, where AC, CT, LD, MA
      and NMB are all represented by '+' in a unified manner. A new method, i.e. the
      combination of least squares regression with '+' (abbreviated as LSR(+)), will be
      introduced for encoding a protein-protein correlation-based feature
      representation and an interacting protein pair. Thus there are totally five
      different combinations for LSR(+), i.e. LSRAC, LSRCT, LSRLD, LSRMA and LSRNMB. As
      a result, we combined a support vector machine (SVM) approach with LSR(+) to
      predict protein-protein interactions (PPI) and PPI networks. The proposed method
      has been applied on four datasets, i.e. Saaccharomyces cerevisiae, Escherichia
      coli, Homo sapiens and Caenorhabditis elegans. The experimental results
      demonstrate that all LSR(+) methods outperform many existing representative
      algorithms. Therefore, LSR(+) is a powerful tool to characterize the protein
      protein correlations and to infer PPI, whilst keeping high performance on
      prediction of PPI networks. 

PMID- 25059330
TI  - A critical analysis of the implementation of service user involvement in primary
      care research and health service development using normalization process theory.
AB  - BACKGROUND: There have been recent important advances in conceptualizing and
      operationalizing involvement in health research and health-care service
      development. However, problems persist in the field that impact on the scope for
      meaningful involvement to become a routine - normalized - way of working in
      primary care. In this review, we focus on current practice to critically
      interrogate factors known to be relevant for normalization - definition,
      enrolment, enactment and appraisal. METHOD: Ours was a multidisciplinary,
      interagency team, with community representation. We searched EBSCO host for
      papers from 2007 to 2011 and engaged in an iterative, reflexive approach to
      sampling, appraising and analysing the literature following the principles of a
      critical interpretive synthesis approach and using Normalization Process Theory.
      FINDINGS: Twenty-six papers were chosen from 289 papers, as a purposeful sample
      of work that is reported as service user involvement in the field. Few papers
      provided a clear working definition of service user involvement. The dominant
      identified rationale for enrolling service users in primary care projects was
      linked with policy imperatives for co-governance and emancipatory ideals. The
      majority of methodologies employed were standard health services research methods
      that do not qualify as research with service users. This indicates a lack of
      congruence between the stated aims and methods. Most studies only reported
      positive outcomes, raising questions about the balance or completeness of the
      published appraisals. CONCLUSION: To improve normalization of meaningful
      involvement in primary care, it is necessary to encourage explicit reporting of
      definitions, methodological innovation to enhance co-governance and dissemination
      of research processes and findings.

PMID- 25059331
TI  - Direct interspecies electron transfer accelerates syntrophic oxidation of
      butyrate in paddy soil enrichments.
AB  - Syntrophic interaction occurs during anaerobic fermentation of organic substances
      forming methane as the final product. H2 and formate are known to serve as the
      electron carriers in this process. Recently, it has been shown that direct
      interspecies electron transfer (DIET) occurs for syntrophic CH4 production from
      ethanol and acetate. Here, we constructed paddy soil enrichments to determine the
      involvement of DIET in syntrophic butyrate oxidation and CH4 production. The
      results showed that CH4 production was significantly accelerated in the presence
      of nanoFe3 O4 in all continuous transfers. This acceleration increased with the
      increase of nanoFe3 O4 concentration but was dismissed when Fe3 O4 was coated
      with silica that insulated the mineral from electrical conduction. NanoFe3 O4
      particles were found closely attached to the cell surfaces of different
      morphology, thus bridging cell connections. Molecular approaches, including DNA
      based stable isotope probing, revealed that the bacterial Syntrophomonadaceae and
      Geobacteraceae, and the archaeal Methanosarcinaceae, Methanocellales and
      Methanobacteriales, were involved in the syntrophic butyrate oxidation and CH4
      production. Among them, the growth of Geobacteraceae strictly relied on the
      presence of nanoFe3 O4 and its electrical conductivity in particular. Other
      organisms, except Methanobacteriales, were present in enrichments regardless of
      nanoFe3 O4 amendment. Collectively, our study demonstrated that the nanoFe3 O4 
      facilitated DIET occurred in syntrophic CH4 production from butyrate, and
      Geobacter species played the key role in this process in the paddy soil
      enrichments.

PMID- 25059332
TI  - Effects of oral moisturising gel containing egg yolk antibodies against Candida
      albicans in older people.
AB  - OBJECTIVE: The aim of this study was to evaluate the inhibitory effects of oral
      moisturising gel containing egg yolk antibody against Candida albicans (anti-CA
      IgY) in older people. Therefore, we measured the number of Candia CFU present on
      oral swabs at baseline and after using the gel. METHODS: A randomised, double
      blind, placebo-controlled trial was conducted among volunteers living in a
      nursing home in Japan. The participants were divided into two groups. The group 1
      participants received oral care using an experimental oral moisturising gel with
      anti-CA IgY, and those in group 2 received oral care using a placebo oral
      moisturising gel without anti-CA IgY. The oral care was performed by care workers
      three times a day for 4 weeks. The participants' tongues were sampled using a
      swab method at baseline and after 2 and 4 weeks of using the oral gel, and the
      number of C. albicans, Candida tropicalis and Candida krusei colonies was
      counted. RESULTS: The baseline oral condition of the participants in the two
      groups did not differ significantly. The experimental gel significantly reduced
      the number of C. albicans colonies from baseline to after 4 weeks of using the
      oral gel; however, no significant reductions were observed in the number of C.
      tropicalis or C. krusei colonies. CONCLUSION: The use of oral moisturising gel
      containing anti-CA IgY for 1 month significantly reduces the number of C.
      albicans CFU present on swabs in older people.

PMID- 25059333
TI  - Use of a point-of-view camera and an Apple iPad to teach direct laryngoscopy to
      trainees.

PMID- 25059334
TI  - Increases in lower-body strength transfer positively to sprint performance: a
      systematic review with meta-analysis.
AB  - BACKGROUND: Although lower-body strength is correlated with sprint performance,
      whether increases in lower-body strength transfer positively to sprint
      performance remain unclear. OBJECTIVES: This meta-analysis determined whether
      increases in lower-body strength (measured with the free-weight back squat
      exercise) transfer positively to sprint performance, and identified the effects
      of various subject characteristics and resistance-training variables on the
      magnitude of sprint improvement. METHODS: A computerized search was conducted in
      ADONIS, ERIC, SPORTDiscus, EBSCOhost, Google Scholar, MEDLINE and PubMed
      databases, and references of original studies and reviews were searched for
      further relevant studies. The analysis comprised 510 subjects and 85 effect sizes
      (ESs), nested with 26 experimental and 11 control groups and 15 studies. RESULTS:
      There is a transfer between increases in lower-body strength and sprint
      performance as indicated by a very large significant correlation (r = -0.77; p =
      0.0001) between squat strength ES and sprint ES. Additionally, the magnitude of
      sprint improvement is affected by the level of practice (p = 0.03) and body mass
      (r = 0.35; p = 0.011) of the subject, the frequency of resistance-training
      sessions per week (r = 0.50; p = 0.001) and the rest interval between sets of
      resistance-training exercises (r = -0.47; p <= 0.001). Conversely, the magnitude
      of sprint improvement is not affected by the athlete's age (p = 0.86) and height
      (p = 0.08), the resistance-training methods used through the training
      intervention, (p = 0.06), average load intensity [% of 1 repetition maximum (RM)]
      used during the resistance-training sessions (p = 0.34), training program
      duration (p = 0.16), number of exercises per session (p = 0.16), number of sets
      per exercise (p = 0.06) and number of repetitions per set (p = 0.48).
      CONCLUSIONS: Increases in lower-body strength transfer positively to sprint
      performance. The magnitude of sprint improvement is affected by numerous subject
      characteristics and resistance-training variables, but the large difference in
      number of ESs available should be taken into consideration. Overall, the reported
      improvement in sprint performance (sprint ES = -0.87, mean sprint improvement =
      3.11 %) resulting from resistance training is of practical relevance for coaches
      and athletes in sport activities requiring high levels of speed.

PMID- 25059335
TI  - Medial retinaculum reefing for the treatment for patellar instability.
AB  - PURPOSE: Medial structures repair is a well-established approach in the treatment
      for patellar instability. However, the literature is confusing concerning the
      indications for surgery, the different surgical techniques and outcomes. The goal
      of this systematic review was to clarify the indications for medial structures
      repair and to analyse the results of both arthroscopic and open techniques.
      METHODS: A comprehensive literature review was performed using the keywords
      'patellar instability', 'medial capsule reefing' and 'medial capsule plication'
      with no limit regarding the year of publication. All the selected articles in
      Anglo-Saxon language were evaluated with the Coleman methodology score. RESULTS:
      Seventeen full-text articles were evaluated. Initial cohort included 617
      patients. About 569 patients were reviewed at an average FU of 54.6 months (range
      2-165 months) after medial structures repair. Average age at the time of surgery
      was 21.2 years (range 9-65 years). The indications for surgery included both
      patellar subluxation and dislocation (acute or chronic). Average Kujala score
      increased from 55 to 84 at the last FU, and in the same way average Lysholm score
      increased from 41.2 to 80.5, whereas average Tegner score increased from 3 to 5.3
      and IKDC score from 47.8 to 75.1. Re-dislocation rate among the series was 6.1%.
      Average Coleman methodology score was 61.6 (range 17-92). CONCLUSION: From this
      review, it emerges that medial capsule reefing is a reliable option in the
      treatment for patellar instability. It can be proposed with good expectations,
      since the outcomes are positive and stable even at longer FU and complications
      rates are low. Re-dislocation rate is variable and can occur in up to one-third
      of patients. However, most of the available studies are case series, and
      comparison of the series is hard since they widely differ in inclusion criteria
      and indications, surgical technique and additional procedures, and outcome
      measures.

PMID- 25059336
TI  - Medial patellofemoral ligament avulsion injury at the patella: classification and
      clinical outcome.
AB  - PURPOSE: To define medial patellofemoral ligament (MPFL) injury characteristics
      at the patellar attachment and clinical outcome in patients with primary
      traumatic patellar dislocation and MPFL avulsion injury at the patella. METHODS:
      Magnetic resonance imaging (MRI) was used to assess patients with primary (first
      time) patellar dislocation and MPFL injury at the medial margin of the patella.
      Fifty-six patients with patellar attachment MPFL injury were enrolled in the
      study. Thirteen patients underwent surgical fixation of the avulsed MPFL and
      patellar medial margin osteochondral fracture, and the remaining patellar MPFL
      injures were treated nonoperatively. Forty-four patients were evaluated
      clinically at median four (range 1-10) years after patellar dislocation. The
      follow-up included evaluation of recurrent patellar instability, subjective
      symptoms, and functional limitations. RESULTS: Three types of patellar MPFL
      injuries were found; type P0 with ligamentous disruption at the patellar
      attachment, type P1 with bony avulsion fracture from the medial margin of the
      patella, and type P2 with bony avulsion involving articular cartilage from the
      medial facet of the patella. Of the patellar MPFL avulsion injuries that
      underwent initial surgical fixation, two patients (2/13) reported an unstable
      patella at follow-up. Fifty-five per cent (17/31) of patellar MPFL avulsion
      injuries that were treated nonoperatively had recurrent patellar instability
      (n.s.). The median Kujala score was 90 for patellar avulsion with surgical
      fixation and 86 for patellar avulsion without surgical fixation (n.s.).
      CONCLUSION: Patellar attachment MPFL injury showed three different patterns,
      classified as types P0, P1, and P2. MRI can be used to assess the injury pattern.
      Patellar MPFL avulsion injuries do not benefit from acute surgical repair
      compared with nonsurgical treatment. Type P2 patellar MPFL avulsion includes an
      osteochondral fracture that may require surgical fixation. LEVEL OF EVIDENCE:
      Prognostic study, Level III.

PMID- 25059337
TI  - Extensive subcutaneous emphysema complicating a percutaneous Mumford procedure.
AB  - Subcutaneous emphysema may be a part of a life-threatening pneumomediastinum or
      pneumothorax and usually does not occur alone. A case of a 75-year-old lady who
      underwent a percutaneous Mumford procedure for acromioclavicular osteoarthrosis
      has been reported. She developed extensive subcutaneous emphysema of the neck,
      chest, bilateral shoulders, and upper arms, in the absence of pneumomediastinum
      or pneumothorax, during the procedure. Isolated subcutaneous emphysema as a
      complication of a percutaneous Mumford procedure has not been reported so far in
      the English literature. The possible mechanism of this complication is discussed.
      Understanding the mechanism is essential in avoiding this preventable
      complication. 

PMID- 25059338
TI  - Preventive lateral ligament tester (PLLT): a novel method to evaluate mechanical
      properties of lateral ankle joint ligaments in the intact ankle.
AB  - PURPOSE: To construct and evaluate an ankle arthrometer that registers inversion
      joint deflection at standardized inversion loads and that, moreover, allows
      conclusions about the mechanical strain of intact ankle joint ligaments at these
      loads. METHODS: Twelve healthy ankles and 12 lower limb cadaver specimens were
      tested in a self-developed measuring device monitoring passive ankle inversion
      movement (Inv-ROM) at standardized application of inversion loads of 5, 10 and 15
      N. To adjust in vivo and in vitro conditions, the muscular inactivity of the
      evertor muscles was assured by EMG in vivo. Preliminary, test-retest and trial-to
      trial reliabilities were tested in vivo. To detect lateral ligament strain, the
      cadaveric calcaneofibular ligament was instrumented with a buckle transducer.
      After post-test harvesting of the ligament with its bony attachments, previously
      obtained resistance strain gauge results were then transferred to tensile loads,
      mounting the specimens with their buckle transducers into a hydraulic material
      testing machine. RESULTS: ICC reliability considering the Inv-ROM and torsional
      stiffness varied between 0.80 and 0.90. Inv-ROM ranged from 15.3 degrees  (+/-7.3
      degrees ) at 5 N to 28.3 degrees  (+/-7.6) at 15 N. The different tests revealed
      a CFL tensile load of 31.9 (+/-14.0) N at 5 N, 51.0 (+/-15.8) at 10 N and 75.4
      (+/-21.3) N at 15 N inversion load. CONCLUSIONS: A highly reliable arthrometer
      was constructed allowing not only the accurate detection of passive joint
      deflections at standardized inversion loads but also reveals some objective
      conclusions of the intact CFL properties in correlation with the individual
      inversion deflections. The detection of individual joint deflections at
      predefined loads in correlation with the knowledge of tensile ligament loads in
      the future could enable more individual preventive measures, e.g., in high-level
      athletes.

PMID- 25059339
TI  - Different femorotibial contact on the weight-bearing: midflexion between normal
      and varus aligned knees after total knee arthroplasty.
AB  - PURPOSE: The influence of residual malalignment on biomechanical analysis after
      total knee arthroplasty (TKA) is currently uncertain. The hypothesis is that
      postoperative alignment would influence the in vivo kinematics after TKA, under
      weight-bearing conditions but not under non-weight-bearing condition. The purpose
      of the present study was to compare weight-bearing and non-weight-bearing
      conditions and to evaluate the effect of the postoperative alignment on the in
      vivo kinematics after posterior cruciate ligament-retaining TKA during midflexion
      using 2-dimensional/3-dimensional registration. METHODS: Thirty knees of 30
      patients with pre-operative varus deformity were divided into 2 groups according
      to their postoperative alignment: the normal alignment group (N = 21) and the
      varus alignment group (N = 9). RESULTS: Under weight-bearing conditions, the
      varus alignment group showed a significant posterior displacement of the medial
      femoral condyle (flexion: 80 degrees , 90 degrees  P < 0.05) and a significant
      anterior displacement of the lateral femoral condyle (flexion: 10 degrees  P <
      0.01, 20 degrees  P < 0.05, and extension: 10 degrees , 20 degrees  P < 0.01, 30
      degrees , 40 degrees  P < 0.05) as compared with the normal alignment group. In
      contrast, no significant difference in the medial and lateral femoral condyle
      positions under non-weight-bearing conditions was observed between the normal and
      varus alignment groups. CONCLUSION: The postoperative alignment influenced knee
      kinematics under weight-bearing conditions. The weight load influenced knee
      kinematics through posterior tibial slope and induced greater lateral femoral
      condyle mobility, which might explain the better clinical and functional outcome.
      These findings contribute to gaining a proper understanding of the in vivo
      kinematics of the postoperative varus alignment and might be useful for
      orthopaedic surgeons in the achievement of patient satisfaction. LEVEL OF
      EVIDENCE: III.

PMID- 25059340
TI  - The percutaneous coronary intervention prior to transcatheter aortic valve
      implantation (ACTIVATION) trial: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Current guidelines recommend treatment of significant coronary artery
      disease by concomitant coronary artery bypass grafting (CABG) in patients
      undergoing surgical aortic valve replacement. However there is no consensus as to
      how best to treat coronary disease in high-risk patients requiring transcatheter
      aortic valve implantation (TAVI). METHODS/DESIGN: The percutaneous coronary
      intervention prior to transcatheter aortic valve implantation (ACTIVATION) trial
      is a randomized, controlled open-label trial of 310 patients randomized to
      treatment of significant coronary artery disease by percutaneous coronary
      intervention (PCI - test arm) or no PCI (control arm). Significant coronary
      disease is defined as >=1 lesion of >=70% severity in a major epicardial vessel
      or 50% in a vein graft or protected left main stem lesion. The trial tests the
      hypothesis that the strategy of performing pre-TAVI PCI is non-inferior to not
      treating such coronary stenoses with PCI prior to TAVI, with a composite primary
      outcome of 12-month mortality and rehospitalization. Secondary outcomes include
      efficacy end-points such as 30-day mortality, safety endpoints including
      bleeding, burden of symptoms, and quality of life (assessed using the Seattle
      Angina Questionnaire and the Kansas City Cardiomyopathy Questionnaire). In
      conclusion, we hope that using a definition of coronary artery disease severity
      closer to that used in everyday practice by interventional cardiologists - rather
      than the 50% severity used in surgical guidelines - will provide robust evidence
      to direct guidelines regarding TAVI therapy and improve its safety and efficacy
      profile of this developing technique. TRIAL REGISTRATION: ISRCTN75836930,
      http://www.controlled-trials.com/ISRCTN75836930 (registered 19 November 2011).

PMID- 25059341
TI  - Elevated odds of metabolic syndrome in psoriasis: a population-based study of age
      and sex differences.
AB  - BACKGROUND: Questions remain concerning to what extent age and sex may modify the
      suggested association between psoriasis and the metabolic syndrome in the general
      population. OBJECTIVES: To investigate the association between psoriasis and the
      metabolic syndrome within a large population-based cohort by age and sex.
      METHODS: A cross-sectional study including 10 521 participants aged 30-79 years
      from the Tromso Study cohort was performed; 1137 participants reported lifetime
      psoriasis of a mainly mild character. The new harmonized definition of metabolic
      syndrome was used in the multivariable logistic regression analysis. RESULTS:
      There was a uniformly higher prevalence of metabolic syndrome in men and women
      with psoriasis compared with those without across all age groups. In women,
      psoriasis was associated with a 3.8-times higher odds of metabolic syndrome at
      age 30 years (95% confidence interval 1.5-9.7), with a decreasing odds ratio with
      increasing age. In men, psoriasis was associated with a stable 1.35-times higher
      odds of metabolic syndrome (95% confidence interval 1.1-1.6) at all ages.
      Abdominal obesity was the most frequent metabolic syndrome component in women in
      this study, and there was indication of a dose-response relationship between
      psoriasis severity, indicated through treatment, and having a high waistline in
      women. CONCLUSIONS: This study suggests age and sex variations in the risk of
      metabolic syndrome among individuals with psoriasis. Given the high prevalence of
      psoriasis and the significantly elevated burden of metabolic syndrome in this
      patient group, there may be a benefit from targeted screening of metabolic
      syndrome among individuals with psoriasis regardless of age and disease severity.

PMID- 25059342
TI  - Targeting IL-6 by both passive or active immunization strategies prevents
      bleomycin-induced skin fibrosis.
AB  - INTRODUCTION: Interleukin-6 (IL-6) is a pleiotropic cytokine for which
      preliminary data have suggested that it might contribute to systemic sclerosis
      (SSc). Our aims were to investigate, firstly, IL-6 expression in patients with
      SSc and, secondly, the efficacy of both passive and active immunization against
      IL-6 to reduce skin fibrosis in complementary mouse models of SSc. METHODS: Human
      serum levels and skin expression of IL-6 were determined by enzyme-linked
      immunosorbent assay and immunohistochemistry, respectively. We first evaluated
      the antifibrotic properties of the monoclonal anti-IL-6R antibody, MR16-1, in the
      bleomycin-induced dermal fibrosis mouse model, reflecting early and inflammatory
      stages of SSc. Then, we assessed the efficacy of MR16-1 in tight skin-1 (Tsk-1)
      mice, an inflammation-independent model of skin fibrosis. Additionally, we have
      developed an innovative strategy using an anti-IL-6 peptide-based active
      immunization. Infiltrating leukocytes, T cells, and B cells were quantified, and
      IL-6 levels were measured in the serum and lesional skin of mice after passive or
      active immunization. RESULTS: Serum and skin levels of IL-6 were significantly
      increased in patients with early SSc. Treatment with MR16-1 led in the bleomycin
      mouse model to a 25% (P = 0.02) and 30% (P = 0.007) reduction of dermal thickness
      and hydroxyproline content, respectively. MR16-1 demonstrated no efficacy in Tsk
      1 mice. Thereafter, mice were immunized against a small peptide derived from
      murine IL-6 and this strategy led in the bleomycin model to a 20% (P = 0.02) and
      25% (P = 0.005) decrease of dermal thickness and hydroxyproline content,
      respectively. Passive and active immunization led to decreased T-cell
      infiltration in the lesional skin of mice challenged with bleomycin. Upon
      bleomycin injections, serum and skin IL-6 levels were increased after treatment
      with MR16-1 and were significantly reduced after anti-IL-6 active immunization.
      CONCLUSIONS: Our results support the relevance of targeting IL-6 in patients with
      early SSc since IL-6 is overexpressed in early stages of the disease. Targeting
      IL-6 by both passive and active immunization strategies prevented the development
      of bleomycin-induced dermal fibrosis in mice. Our results highlight the
      therapeutic potential of active immunization against IL-6, which is a seductive
      alternative to passive immunization.

PMID- 25059343
TI  - Does neoadjuvant therapy for esophageal cancer increase postoperative morbidity
      or mortality?
AB  - Neoadjuvant therapy has proven to be effective in the reduction of locoregional
      recurrence and mortality for esophageal cancer. However, induction treatment has
      been reported to be associated with increased risk of postoperative
      complications. We therefore compared outcomes after esophagectomy for esophageal
      cancer for patients who underwent neoadjuvant therapy and patients treated with
      surgery alone. Using the American College of Surgeons National Surgical Quality
      Improvement Program database (2005-2011), we identified 1939 patients who
      underwent esophagectomy for esophageal cancer. Seven hundred and eight (36.5%)
      received neoadjuvant therapy, while 1231 (63.5%) received no neoadjuvant therapy
      within 90 days prior to surgery. Primary outcome was 30-day mortality, and
      secondary outcomes included overall and serious morbidity, length of stay, and
      operative time. Patients who underwent neoadjuvant treatment were younger (62.3
      vs. 64.7, P < 0.001), were more likely to have experienced recent weight loss
      (29.4% vs. 15.9%, P < 0.001), and had worse preoperative hematological cell
      counts (white blood cells <4.5 or >11 * 10(9) /L: 29.3% vs. 15.0%, P < 0.001;
      hematocrit <36%: 49.7% vs. 30.0%, P < 0.001). On unadjusted analysis, 30-day
      mortality, overall, and serious morbidity were comparable between the two groups,
      with the exception of the individual complications of venous thromboembolic
      events and bleeding transfusion, which were significantly lower in the surgery
      only patients (5.71% vs. 8.27%, P = 0.027; 6.89% vs. 10.57%, P = 0.004;
      respectively). Multivariable and matched analysis confirmed that 30-day
      mortality, overall, and serious morbidity, as well as prolonged length of stay,
      were comparable between the two groups of patients. An increasing trend of
      preoperative neoadjuvant therapy for esophageal cancer was observed through the
      study years (from 29.0% in 2005-2006 to 44.0% in 2011, P < 0.001). According to
      our analysis, preoperative neoadjuvant therapy for esophageal cancer does not
      increase 30-day mortality or the overall risk of postoperative complications
      after esophagectomy. 

PMID- 25059344
TI  - Clinicopathological factors predicting R0 resection and long-term survival after
      esophagectomy in patients with T4 esophageal cancer undergoing induction
      chemotherapy or chemoradiotherapy.
AB  - PURPOSE: To identify clinicopathological factors predicting R0 resection and long
      term survival after esophagectomy in patients with T4 esophageal cancer following
      induction chemotherapy or chemoradiotherapy. METHODS: Of 48 patients with T4
      esophageal cancer who underwent induction treatment, 30 underwent R0
      esophagectomy. The factors predicting R0 resection and prognostic indicators were
      assessed in the 48 and 30 patients, respectively, using univariate and
      multivariate analyses. RESULTS: In the univariate analyses, the primary tumor
      response, improvement of dysphagia, the post-induction therapy Glasgow Prognostic
      Score, an early tumor response and the post-induction therapy serum albumin and C
      reactive protein levels were significantly correlated with R0 resection.
      Multivariate logistic regression analyses revealed that the response status and
      improvement of dysphagia were independent predictors of R0 resection. The
      univariate analyses identified a yp-T classification (yp-T0/1 vs. yp-T2/3/4), yp
      nodal status and the number of pathologically positive nodes post-therapy (<= 1
      vs. >= 2) as significant prognostic factors. The multivariate analysis revealed
      that the number of pathologically positive nodes was the only significant
      independent prognostic indicator. CONCLUSION: Patients showing an early tumor
      response to induction treatment and improvement of dysphagia may be appropriate
      candidates for esophagectomy, and individualized postoperative management
      strategies should be developed for patients with initially unresectable T4
      esophageal cancer who have >= 2 positive nodes post-treatment.

PMID- 25059345
TI  - Correlation between obesity and clinicopathological factors in patients with
      papillary thyroid cancer.
AB  - PURPOSE: Epidemiological studies have shown that obesity is associated with an
      increased risk of thyroid cancer. However, the exact nature of the relationship,
      especially with respect to the behavior of the cancer, remains uncertain. The
      objective of this study was to evaluate the correlation between the body mass
      index (BMI) and clinicopathological features of thyroid cancer patients. METHODS:
      From January 2009 to April 2010, 716 consecutive patients (602 females and 114
      males; mean age 47.02 +/- 11.73 years) with papillary thyroid cancer (PTC) were
      analyzed retrospectively. Patients were divided into two subgroups according to
      age (<45 years, >=45 years). The BMI groupings were based on standardized
      categories set by the World Health Organization. The relationships between the
      BMI and these parameters were assessed. RESULTS: A non-overweight BMI was
      associated with a younger age and female gender. Tumor multiplicity was related
      to a higher BMI. In an age-related subgroup analysis, a higher BMI was correlated
      with more lymph node involvement (p = 0.004), lymphatic invasion (p = 0.003) and
      tumor multiplicity (p = 0.008) in patients >=45 years of age. The absence of an
      association between the BMI and T stage, nodal status, vascular invasion,
      lymphatic invasion, and extrathyroidal extension was noted in a statistical
      analysis. In the subgroup of patients <45 years of age, no positive associations
      were observed between the BMI and any parameters other than age and sex.
      CONCLUSIONS: In PTC patients >=45 years of age, a higher BMI was associated with
      more aggressive tumor features, such as lymph node metastasis, lymphatic
      invasion, and tumor multiplicity.

PMID- 25059346
TI  - Proposal of a new prognostic staging system for pulmonary metastases from
      colorectal cancer.
AB  - PURPOSE: The aim of this retrospective study was to establish a new prognostic
      staging system for pulmonary metastases from colorectal carcinoma (CRC). METHODS:
      The baseline characteristics and outcomes on 352 CRC patients who underwent
      complete pulmonary resection were collected from 19 institutions by the Japanese
      Society for Cancer of the Colon and Rectum (JSCCR) Study Group (group A). The
      clinical and pathological factors were entered into a multivariate analysis to
      identify independent variables that were helpful for accurately predicting the
      long-term prognosis after pulmonary resection. Using the selected variables in
      group A, we developed a new prognostic staging system (PSS). The new PSS was
      examined in a validation study in a series of 841 patients from 110 institutions
      of the JSCCR by the 78th society of the JSCCR (group B). RESULTS: We evaluated
      four variables selected in the multivariate analysis: the number of pulmonary
      metastases, the distribution, the disease-free interval and the lymph node
      metastases of primary cancer in group A. Using these four variables, we developed
      a new PSS. This PSS was found to significantly predict the prognosis in group B.
      CONCLUSIONS: Our new PSS was useful for the selection of patients suitable for
      pulmonary resection.

PMID- 25059347
TI  - Single-incision thoracoscopic surgery using a chest wall pulley for lung excision
      in patients with primary spontaneous pneumothorax.
AB  - PURPOSE: The aim of the study was to evaluate the feasibility and compare the
      outcomes of single-incision thoracoscopic surgery using a chest wall pulley for
      lung excision (PulLE) vs. those of conventional video-assisted thoracic surgery
      (cVATS) in patients with primary spontaneous pneumothorax (PSP). METHODS: Sixty
      nine patients who underwent PulLE (n = 34) or cVATS (n = 35) between January 2009
      and December 2013 were enrolled in this study. PulLE was performed as follows.
      After making a 17- to 25-mm single incision in the 6th intercostal space (6ICS)
      at the median axillary line, the visceral pleura near the bulla was sutured for
      traction. The parietal pleura at 3ICS was then sutured from the thoracic cavity
      to serve as the chest wall pulley and a traction thread was passed through the
      pulley. By manipulating the traction thread, it was possible to move the lesion
      to an arbitrary site for excision. The postoperative scar was nearly invisible.
      RESULTS: The operative time, duration of postoperative drainage, and
      postoperative hospital stay were equivalent for PulLE vs. cVATS. There was no
      significant difference in postoperative recurrence rates. CONCLUSIONS: PulLE has
      cosmetic benefits over cVATS and is easy to perform. We believe our novel
      procedure has the potential to become the standard operative treatment for PSP.

PMID- 25059348
TI  - Hepatic resection for hepatocellular carcinoma in a patient with situs ambiguous
      with polysplenia: report of a case.
AB  - We report a case of successful resection of hepatocellular carcinoma (HCC) in a
      patient with situs ambiguous with polysplenia (PS), a rare congenital anomaly. A
      62-year-old Japanese man was admitted to our hospital for investigation and
      treatment of a hepatic tumor. Imaging studies revealed two HCCs, 2.5 and 0.7 cm
      in diameter, in the anterior section and segment 3 of the reversed liver,
      respectively. He also had multiple spleens in the right side of the abdomen,
      right side of the stomach, and duodenum, as well as azygous continuation of the
      inferior vena cava (IVC) with absence of the retro-hepatic IVC, a truncated
      pancreas, rare variation of the hepatic artery, and dextrocardia. We performed
      anterior sectionectomy of the liver and partial resection of segment 3. We found
      only two previous reports of HCC in patients with situs ambiguous with PS, but
      our patient is the first to have undergone anatomical hepatic resection of the
      reversed liver. Accurate anatomical assessment is essential during surgery on
      such patients. 

PMID- 25059349
TI  - Supplementation of IVF medium with melatonin: effect on sperm functionality and
      in vitro produced bovine embryos.
AB  - Gamete co-incubation generates high free radical levels surrounding growing
      zygotes which may impair subsequent embryo viability. Melatonin eliminates a wide
      variety of free radicals; hence, we tried to improve in vitro embryo production
      by adding melatonin to in vitro fertilisation (IVF) media in high (Exp. 1) and
      low concentrations (Exp. 2), and we evaluated its effect on bull sperm function
      during IVF co-incubation time (Exp. 3). In Experiment 1, we supplemented IVF
      media culture with 0.01, 0.1 and 1 mmol of melatonin, along with a no melatonin
      control group. In Experiment 2, melatonin levels were reduced to 10, 100 and 1000
      nmol, with a no melatonin control group. In Experiment 3, spermatozoa were
      incubated in IVF media with melatonin (as Exp. 2) and functional parameters were
      analysed at 0, 4 and 18 h. In Experiment 1, only 1 mmol melatonin showed lesser
      blastocyst rates than control (C: 23.2 +/- 6.7% versus 1 mmol: 2.0 +/- 1.7%). In
      Experiment 2, no statistical differences were found in cleavage percentage,
      blastocyst percentage and total cell count for any melatonin treatment. In
      Experiment 3, sperm samples with 1000 nmol melatonin had a significantly higher
      wobbler (WOB) coefficient, a lower percentage of intact acrosomes, a lower
      percentage of viable spermatozoa with ROS, greater DNA fragmentation and higher
      DNA oxidation than controls. Total fluorescence intensity for ROS at 10 nmol
      melatonin was significantly greater than controls (P < 0.05). IVF media with 1
      mmol melatonin is deleterious for embryo development, and in lower
      concentrations, it modulated sperm functionality, but had no effects on embryo
      production. 

PMID- 25059350
TI  - [Prevention and control of the social behavior associated infectious by changing
      social behavior].

PMID- 25059351
TI  - [Relationship between current smoking behaviors and household characteristics in
      Guangdong].
AB  - OBJECTIVE: To disclose the relationship between current smoking behaviors and
      household characteristics among adults in Guangdong, in order to provide
      scientific evidence for household tobacco control strategy. METHODS: A
      questionnaire survey was conducted among the adults sampled by four-stage
      randomized cluster sampling in ten districts of five cities in Guangdong from
      September to November, 2010. The questionnaire included demographic
      characteristics, smoking behaviors and smoking-related household characteristics.
      Chi-square test and unconditional logistic regression analysis were employed to
      explore the relationship between current smoking behaviors and household
      characteristics. RESULTS: This study included 2 150 respondents, with data from 2
      121 eligible questionnaires used for analysis. The current smoking rates for
      respondents with household characteristics including per capita household income
      below 1 000 Yuan, three or more smokers in the family, no ban of smoking at home
      and treating visitors with cigarettes were 28.7%, 56.5%, 34.2% and 43.5% ,
      respectively, and were significantly higher than those for respondents with
      household characteristics at other levels (P < 0.01 for all). After controlling
      for factors such as gender, age, personal income, education, employment status
      and residential location, we found that the number of family smokers, smoking
      restrictions at home and treating visitors with cigarettes had significant
      association with current smoking behaviors (P < 0.01 for all), except for per
      capita household income (P = 0.567). CONCLUSION: Household is one of the
      effective places in carrying out health education and tobacco control
      intervention. In order to reduce tobacco use, much effort should be made to
      create smoke-free homes, encourage smoking cessation and treat visitors with no
      cigarettes.

PMID- 25059352
TI  - [Situation of domestic violence and health outcomes among married migrant women
      at reproductive age].
AB  - OBJECTIVE: To examine the association between domestic violence and
      mental/general health status among married migrant women at reproductive age.
      METHODS: A total of 958 eligible married migrant women of reproductive age who
      were selected through community-based multiple-stage sampling method in one urban
      district in Shanghai and interviewed in April and May 2010. Chi-square test,
      Fisher's exact test and unconditional logistic regression model were used for
      data analysis. RESULTS: The overall prevalence of domestic violence in husbands
      was 40.0%. Among 5 adverse outcomes related to general health and 6 adverse
      outcomes related to mental health, exposing to physical or sexual violence in the
      life time or in the previous year were associated with 2 adverse outcomes related
      to general health (including often in pain/discomfort and sleeping problems) and
      4 adverse outcomes related to mental health (including often feeling
      nervous/tense/worry, easily getting frightened, crying more than usual, often
      feeling worthless on herself or being indifferent to the surroundings).
      Experience of control behavior was associated with 1 adverse outcome that related
      to general health (often in pain or discomfort) and 3 adverse outcomes related to
      mental health including easily get frightened, feeling worthless on herself or
      indifferent to the surroundings, Experience of emotional violence in the previous
      year was associated with pain or discomfort feelings. Compared with those who had
      never experienced any violence from husband after adjusting for potential
      influencing factors in logistic regression models, respondents who had ever
      experienced physical or sexual violence, control behavior or emotional violence,
      the numbers were respectively, presented 2.25-3.70 times, 1.94-4.75 times and
      2.12 times, more likely to report the above-mentioned adverse health outcomes.
      CONCLUSION: Domestic violence was associated with general and mental health among
      married migrant women at reproductive age, especially physical or sexual violence
      and control behaviors.

PMID- 25059353
TI  - [Change of risky sexual behaviors among men who have sex with men before and
      after recent identification of HIV diagnosis].
AB  - OBJECTIVE: To assess the change of sexual behaviors before and after HIV was
      recently identified among men who have sex with men (MSM). METHODS: A
      retrospective study was conducted on recently identified HIV-infected MSM in
      Chengdu and Tianjin. A face-to-face questionnaire interview was administrated to
      collect sexual behaviors within six months, before and after HIV was diagnosed.
      Differences in sexual behavior before and after the diagnosis were assessed,
      using the McNemar chi(2) test. Logistic regression analysis was conducted to
      identify predictors for sexually risk behaviors. RESULTS: Of 129 HIV-infected MSM
      under survey, the average age was 31.8 years and the main venue in seeking male
      sex partners was through Internet. The proportions of MSM with unprotected anal
      intercourse (UAI) decreased from 70.5% before diagnosis to 16.3% after diagnosis
      and the percentage of having more than 1 partner decreased from 66.7% before
      diagnosis to 33.3% after diagnosis. After the diagnosis was made, there appeared
      a significant decrease in the percentage of persons who had one main partner from
      72.9% to 55.0% and having casual partners declined from 62.8% to 31.0% . Data
      from multiple logistic regression analysis revealed that risk factors as UAI
      before diagnosis, more than 1 partner after diagnosis and having one main
      partner, were all significantly associated with UAI after diagnosis. After the
      diagnosis was made for UAI, risk factors for 'having more than 1 partner' after
      diagnosis, would include:using Internet to seek for sexual partners, after
      diagnosis, having one main partner but not disclosing to him. CONCLUSION: After
      the diagnosis was made, most HIV-infected MSM would reduce their high risk sexual
      behaviors but some continued to practice UAI.

PMID- 25059354
TI  - [Relationship between 'ideal' cardiovascular behaviors and factors and the
      incidence of hypertension].
AB  - OBJECTIVE: To explore the relationship between 'ideal' cardiovascular behaviors
      and factors and the incidence of hypertension. METHODS: A prospective cohort
      study including 52 133 workers who had participated in the 2006-2007 Kailuan
      health examination without history of cerebral infraction, myocardial infarction
      or hypertension but with complete data, was carried out. All workers were
      followed on their occurrence of hypertension. According to the AHA definition of
      'ideal' cardiovascular health behaviors and factors, the cumulative incidence
      rates of hypertension in different groups were calculated under the life table
      method, and compared by Log-rank test, Cox proportional hazards regression was
      used to calculate the hazard rations and 95% confidence intervals for baseline
      behaviors and factors. RESULTS: The cumulative incidence rates of hypertension
      according 0-1, 2, 3, 4, 5-7 ideal cardiovascular health behaviors and factors
      were 65.72%, 59.14%, 54.59%, 50.24% and 34.22%, respectively in the 0-1, 2, 3, 4,
      5-7 groups. Data from the Cox proportional hazards model showed that after
      adjusting for age, education level and family history of hypertension, the ones
      who had 2, 3, 4, 5-7 ideal cardiovascular behaviors/factors were 0.75, 0.69,
      0.63, 0.36 times more than those who had 0-1 ideal behaviors. CONCLUSION: The
      incidence of hypertension and risk reduced along with the increase of ideal
      cardiovascular health behaviors and factors.

PMID- 25059355
TI  - [Relationship between socioeconomic status and the prevalence of cardiovascular
      disease among retired residents living in a community, Shanghai].
AB  - OBJECTIVE: To explore the relationship between socioeconomic status and the risk
      factors of cardiovascular diseases in retirees from a community in Shanghai.
      METHODS: Observational study involved 9 943 retirees aged 50 and over in
      Shanghai. Both single factor and multi-factor analyses methods were used to
      describe the correlation between factors as:educational level, marital status,
      annual household income and risk of hypertension, coronary heart disease, stroke
      etc. A new defined compound index was used to assess the relevance of
      socioeconomic status on the risk of cardiovascular diseases, based on logistic
      regression model. RESULTS: After adjusted for age, the risk of cardiovascular
      diseases in these retirees was influenced by socioeconomic status. In general,
      opponent correlations in education levels and prevalence of hypertension were
      found between female and male. Compared with those having received college or
      higher education, the risk of hypertension increased in females when the
      education level declined, with OR as 1.08 (95% CI:0.89-1.30). For those having
      had senior high school junior high school or elementary education, the risks of
      hypertension were 1.26 (95%CI:1.05-1.51), 1.34 (95%CI:1.08-1.65), 0.72
      (95%CI:0.59-0.87),0.78 (95%CI:0.64-0.94), and 0.70 (95%CI:0.52-0.92) for males,
      respectively. The risk of cardiovascular diseases increased with annual household
      income. Compared with high level of socioeconomic status, lower socioeconomic
      status might decline the risk of cardiovascular diseases in males by
      approximately 30%, with OR for medium being 0.72 (95%CI:0.61-0.84) and for lower
      ones it was 0.70 (95% CI:0.57-0.87). However, similar correlations were not found
      in females. No significant relationship was found between marital status and the
      prevalence of cardiovascular diseases in this study. CONCLUSION: The risks of
      cardiovascular diseases varied with different socioeconomic status, indicating
      that tailored interventions should be conducted in different socioeconomic
      groups.

PMID- 25059356
TI  - [Depressive symptoms and related factors among primary and middle school students
      in Changfeng county of Anhui province:a two-year longitudinal study].
AB  - OBJECTIVE: To assess the prevalence of depressive symptoms, trends on its
      longitudinal development and related influencing factors among primary and middle
      school students in Changfeng county of Anhui province. METHODS: Through cluster
      sampling methods, all students from 3 to 9 grades in 5 primary schools and 3
      middle schools in Changfeng county of Anhui province were investigated through
      questionnaire as subjects of baseline survey in December 2009. Subjects of this
      longitudinal study were students in grades 3, 4 and 7 at the time of the baseline
      survey and were contacted once a year for two years. At last, a total of 816
      students participated in all the three surveys. A structured questionnaire
      including Children's Depression Inventory, socio-demographic characteristics and
      some potential influential factors was employed for this study. A Generalized
      Estimating Equation (GEE) was used to evaluate the related influencing factors of
      children's depressive symptoms in the longitudinal study. RESULTS: Prevalence
      rates of depressive symptoms were 11.3% , 10.4% and 8.5% , respectively, at the
      baseline, 1-year and 2-year follow-up studies, among primary and middle school
      students. Scores on depressive symptoms of total subjects and children who had
      always been left at home in the follow-up process showed significant differences
      at the three surveys (F = 13.423, P < 0.001; F = 5.761, P = 0.003). 25 percent of
      the 92 students who showed depressive symptoms at the baseline survey remained
      those depressive symptoms at the 1-year follow-up study and 87 percent of the 23
      students who had depressive symptoms at the baseline and 1-year follow-up surveys
      still showing depressive symptoms at the 2-year follow-up study. Results from the
      GEE program indicated that grade 3 students, having syblings, family with
      dysfunction or at low level of self-esteem etc., were prone to development while
      sex and parents' educational level were not correlated with depressive symptoms.
      CONCLUSION: Prevalence of depressive symptoms among primary and middle school
      students in Changfeng county of Anhui province appeared a decreasing tendency
      during the follow-up process in our study. Through the longitudinal development,
      we noticed that the prevalence of depressive symptoms seemed to be related to the
      personal characteristics, education and family environment of the subjects under
      our study. Improving the level of family function as well as individual's self
      esteem might positively contribute to mental health of those primary and middle
      school students.

PMID- 25059357
TI  - [Prevalence of HIV and sexually transmitted diseases as well as related
      associated risk factors among middle/low level female sex workers in a city in
      Guangdong province].
AB  - OBJECTIVE: To explore the prevalence of HIV, sexually transmitted diseases (STDs)
      and associated factors among medium/low level female sex workers (FSWs) in an
      under-developed city in Guangdong province. METHODS: FSWs were reached by
      probability proportionate to size sampling through mapping. A cross-sectional
      survey was conducted to investigate data on demographic characteristics, sexual
      behaviors, condom use and drug use. 5 ml blood samples were collected to test for
      human immunodeficiency virus(HIV), syphilis and HSV-2. RESULTS: The prevalence
      rates of HIV, syphilis and HSV-2 were 0.3% (2/575), 4.9% (28/575) and 30.6%
      (176/575) respectively, and 32.2% (185/575)for STDs. Results from multivariate
      unconditional logistic regression model indicated that drug use (OR = 3.91, 95%
      CI:1.17-13.03) was the independent risk factor for STDs infection. Risks as ever
      accepted intervention program (OR = 0.14, 95% CI:0.04-0.52), with higher
      education level (OR = 0.40, 95% CI:0.19-0.83)and medium-fee charged FSWs(OR =
      0.27, 95% CI:0.09-0.79) were protective factors for STDs. CONCLUSION: Sources of
      STDs and related risk factors were comprehensive among medium/low FSWs,
      especially for the latter, with all calling for multi-sector cooperation to
      explore the effective intervention program in this population.

PMID- 25059358
TI  - [Distribution of serum antibodies against human papillomavirus 16 and 18 among
      high-risk women to cervical cancer].
AB  - OBJECTIVE: To explore the distribution of serum antibodies against human
      papillomavirus (HPV) 16/18 among women at high-risk for cervical cancer. METHODS:
      All women when tested positive for anyone of the cervical cancer screening
      programs, from Xinmi county of Henan province in 2011, were recruited as the
      subjects of this study. Cervical exfoliated cells were collected, using cervical
      brush for HPV DNA testing, and 10 ml venous blood was drawn for HPV-16, 18 serum
      antibodies testing, by enzyme-linked immunosorbent assay. RESULTS: Among the 952
      women under study, 230 cases (24.2%)showed HPV DNA positive, with positivity
      rates of HPV16 and 18 L1 virus-like particle (VLP)antibodies as 23.2% and 6.5%,
      respectively. The overall positivity rate of any type of HPV16, 18 VLP antibodies
      was 26.8% . Geometric means of HPV16, 18 VLP antibody titers were 79.1
      (Yangshengtang Unit,YU/ml) and 125.0(YU/ml). Positivity rate of HPV16 antibody
      was significantly associated with age, viral load of HPV DNA, and cervical lesion
      severity (P < 0.05). Seropositivity of HPV18 was also increasing with the
      increase of viral load (P < 0.01) with different cervical lesion significantly
      showing different titer of HPV18 antibody (P < 0.01). Based on the results of HPV
      DNA detection among the two years of study, women with HPV persistent infection
      showed significant higher positive rate of HPV16/18 antibodies than women who did
      not have HPV infection or emerging infection (P < 0.001). When comparing to those
      women without HPV infection, the ones with transient infection showed higher
      seropositivity rates on both HPV16 antibodies and titer of HPV16 antibody (P <
      0.001). CONCLUSION: Seroprevalence rates on HPV16 and 18 among the unvaccinated
      high-risk women in Henan were high. Prevalence of both HPV16 and 18 antibodies
      were correlated with age, viral load, cervical lesion and history of
      infection.Women with high viral load, high grade cervical lesion or history of
      infection would more likely to be seropositive.

PMID- 25059359
TI  - [Characterization of antimicrobial resistances and molecular characteristics of
      Salmonella isolates from the pork production chain in Sichuan province, 2010
      2011].
AB  - OBJECTIVE: To investigate the antimicrobial resistance and resistance profiles of
      Salmonella isolates, from the pork production chain in several districts of
      Sichuan province and to determine the correlation between serotype and the pulse
      field gel electrophoresis (PFGE) patterns. METHODS: From 2010 to 2011, a total of
      112 Salmonella isolates from pork production chain were examined for their
      antimicrobial susceptibility, using the micro-dilution method against 10
      antimicrobial agents. RESULTS: were assessed by the standard by the Clinical and
      Laboratory Standards Institute (CLSI, 2010). In addition, PFGE patterns were
      investigated among the Salmonella strains from different sources, under different
      serovars and antimicrobial profiles. RESULTS: For Salmonella isolated from the
      pork production chain, resistance to tetracycline (89.29%) was frequently
      observed. Many isolates were resistant to spectinomycin (36.61%),
      trimethoprim/sulfamethoxazole (35.71%), nalidixic acid (33.93%) and ampicillin
      (24.11%), but all of the isolates were susceptible to ceftiofur. 33.93% of the
      isolates were multi-drug resistant. Salmonella isolates from the pork production
      chain had 19 antibiotic resistance profiles. Totally, 34 PFGE patterns were
      detected among 74 Salmonella isolates from the pork production chain, with the
      PFGE patterns of the 74 Salmonella isolates sharing 40% to 100% similarities.
      CONCLUSION: The antimicrobial resistances of the Salmonella isolates were
      commonly detected from the pork production chain in Sichuan province suggesting
      that Salmonella might horizontally spread from food animals to retail meat
      products.

PMID- 25059360
TI  - [Prevalence and homology analysis on human and animals severe fever with
      thrombocytopenia syndrome virus infection in Yantai of Shandong province].
AB  - OBJECTIVE: To learn the prevalence of infection of human and animals severe fever
      with thrombocytopenia syndrome bunyavirus (SFTSV) in Yantai, Shandong province,
      and to analyze the pathogenic features of SFTSV as well as its relationship
      between human and animal hosts. METHODS: From April to November in 2011, 3 576
      serum samples were collected from domesticated animals, including sheep, cattle,
      pigs, dogs, chickens, in Laizhou and Penglai areas where fever with
      thrombocytopenia syndrome frequently occurred among local residents. Total SFTSV
      antibodies and virus-specific nucleic acids of the serum were tested by ELISA and
      Real time RT-PCR, respectively. SFTSV infection on each animal was observed in
      different months. 2 590 human serum samples were also collected in Laizhou and
      Penglai areas, with IgG antibodies tested by ELISA. Virus was isolated with Vero
      cells from the serum which SFTSV viral nucleic acids were positive. S fragments
      were amplified by RT-PCR and sequenced, with homology analysis conducted on these
      sequences. RESULTS: The overall positive rate of serum samples from animals on
      the total SFTSV antibodies was 40.24% (1 439/3 576) while the positive rate for
      specific nucleic acids was 4.56% (163/3 576). The positive rates for SFTSV
      antibodies were 62.78%, 52.97%, 45.56%, 28.73%, 1.45% and the positive rates for
      specific nucleic acids were 5.72%, 4.63%, 3.02%, 5.25% and 3.73%, in sheep,
      cattle, chickens, dogs, pigs, respectively. The antigens/antibodies for SFTSV in
      animals changed seasonally. The overall positive rate for SFTSV IgG antibody from
      2 590 human samples was 5.41%. Thirteen virus strains were isolated from these
      serum samples (10 strains from human and 3 strains from animals). The nucleotide
      homology of 13S fragments' sequences ranged from 95.23% to 100.00% and the
      nucleotide homology with the isolates from other provinces were between 94.72%
      and 99.13%. The homology was considered to be high. CONCLUSION: High prevalence
      of SFTSV infections occurred both in human and domestic animals in Yantai city.
      The nucleotide sequences of SFTSV were highly homologous among human and domestic
      animals. The findings suggested that domesticated animals might serve as SFTSV
      proliferation and the hosts for transmission thus should be attached great
      importance.

PMID- 25059361
TI  - [Investigation on mosquitoes and mosquito-borne viruses in Dehong prefecture,
      Yunnan province, 2007 and 2010].
AB  - OBJECTIVE: To investigate the distribution patterns of mosquito and mosquito
      borne viruses in Dehong prefecture, Yunnan province, China. METHODS: Mosquito
      samples were collected using the mosquito traps from five counties of Dehong
      prefecture on July, 2007 and 2010. Mosquito were cell cultured for viral
      isolation, and positive isolates were identified using RT-PCR and sequence
      analysis. RESULTS: A total of 43 634 mosquito comprised of 29 species
      representing six genera were collected. Culex tritaeniorhynchus and Anopheles
      sinensis comprised 78.69% and 14.77% of the total. Six strains of viruses were
      isolated from the mosquito pools. RT-PCR and phylogenetic analysis revealed three
      strains from Cx. tritaeniorhynchus, identified as genotype I Japanese
      encephalitis virus (JEV). One strain was identified from Cx. tritaeniorhynchus,
      as Getah virus (GETV). Two strains isolated from Cx. tritaeniorhynchus and
      Anopheles vagus were identified as Culex pipiens pallens Densovirus (CppDNV).
      CONCLUSION: Cx. tritaeniorhynchus had been the major species of mosquito and
      mainly transmitting vector of mosquito-borne viruses in Dehong prefecture.
      Genotype I JEV, GETV and CppDNV were the vectors causing transmission of mosquito
      borne diseases in this area. Data from phylogenetic analysis showed that these
      newly discovered isolates seemed to have had close relationship with those
      viruses previously circulating in Yunnan and other provinces of China.

PMID- 25059362
TI  - [Interaction of prenatal care and level of maternal education on the risk of
      neonatal low birth weight].
AB  - OBJECTIVE: To investigate the interaction of prenatal care indexes including
      weeks of initiation of prenatal care, number of prenatal care visits and maternal
      educational level on the risk of neonatal low birth weight (LBW). METHODS:
      Logistic Regression Model was performed to estimate the association including the
      interaction with OR and 95%CI between prenatal care indexes and LBW risk in all
      the subjects. Three educational levels(junior high, senior high, junior college)
      of mothers were also assessed. New variables of the prenatal care indexes were
      transformed using the quartiles, according to the distribution of the original
      variables on pregnant women with newborns of normal birth weight. RESULTS:
      Whether the pregnant women were stratified by educational level, with the
      increasing number of prenatal care visits, LBW risk was shown a U-type tendency
      in different strata of educational levels, when comparing with the reference
      group, respectively. Compared to the baseline group, the OR and 95% CI of the
      third quartile on number of prenatal care visits were 0.48 (0.35-0.64), 0.55
      (0.32-0.95), 0.50 (0.32-0.80), 0.36(0.20-0.66) in all subjects who had received
      educational levels as junior middle school, senior middle school or junior
      college degree ect., respectively. A significant interaction was shown between
      the number of prenatal care visits and maternal educational level on the neonatal
      LBW risk (chi2 = 4.650 2, P = 0.031 1). However, no interaction was found between
      the week of initiation of prenatal care and maternal educational level on the
      neonatal LBW risk (chi2 = 0.929 7, P = 0.334 9). CONCLUSION: Data from our study
      indicated that there was a protective interaction on reducing the neonatal LBW
      risk between maternal educational level and the number of prenatal care visits,
      but not the weeks on the initiation of prenatal care. More prenatal care programs
      should be implemented among the pregnant women with lower educational level.

PMID- 25059363
TI  - [Impact factors on physical activity level among the urban junior high school
      personnel in Hangzhou].
AB  - OBJECTIVE: To explore the level of physical activities (PA) and related
      influencing factors among junior high school personnel in Hangzhou. METHODS: In a
      cross sectional study, a self administered questionnaire was used to assess the
      levels of PA. Kruskal-Wallis H test and ordinal regression were applied to
      analyze the related factors. RESULTS: Among the 1 497 school personnel included
      in this study, prevalence rates on the low, moderate and high levels of PA were
      40.8%, 40.6% and 18.6%, respectively. Data from the multinomial logistic
      regression analysis indicated that:when comparing with the low level, people aged
      >= 45 (OR = 1.576, 95% CI:1.128-2.201) or those having minor perceived stress (OR
      = 1.490, 95% CI:1.141-1.946) more likely to fall into the moderate level.
      However, factors as higher awareness scores on the benefit of PA (OR = 1.070,
      95%CI:1.002-1.143), being male (OR = 3.088, 95%CI:2.162-4.409), always or very
      often taking PA together with colleagues (OR = 2.903, 95%CI:1.587-5.312), taking
      PA once in a while together with colleagues (OR = 1.900, 95%CI:1.160-3.110) or
      having space to walk around home (OR = 1.657, 95% CI:1.022-2.688) would increase
      the likelihood of having high PA level. However, factors as marital status,
      socioeconomic status, years of working at school, BMI, level of having received
      education and positive impact from colleagues etc. did not seem to have
      significantly related to the PA level. CONCLUSION: Gender, age, stress from work
      and supportive environment should be taken into account while planning on
      promoting the PA level among junior high school personnel in Hangzhou.

PMID- 25059364
TI  - [Trend on HIV prevalence and risk behaviors among men who have sex with men in
      China from 2010 to 2013].
AB  - OBJECTIVE: To understand the trends on HIV and syphilis infections, as well as on
      risk behaviors and intervention among MSM in China from 2010 to 2013 so as to
      provide information for the development of intervention strategies for MSM.
      METHODS: Study population involved MSM who were recruited for the national HIV
      sentinel surveillance between 2010 and 2013. Demographic information, HIV related
      risk behaviors, and results on HIV and syphilis infections were described and
      trend analysis was performed. RESULTS: Between 2010 and 2013, the total number of
      MSM under survey was 149 848. As for sources of the studied population, 12.3% of
      them were from public bathrooms (Group A), 30.1% from internet (Group B), and
      57.5% were others (Group C). Proportions of three groups were similar between
      2010 and 2013. The proportion of always using condom in the last six months
      increased from 30.2% to 37.8%, from 34.7% to 42.9% and from 35.3% to 43.1% in
      group A, B or C (trend:P < 0.01), from 2010 to 2013. The proportion of using
      condom in group A was the lowest among the three groups. The prevalence rate of
      HIV increased from 7.8% in 2010 to 9.2% in 2013 among group A, from 5.0% in 2010
      to 6.8% in 2013 among group B, from 5.6% in 2010 to 6.5% in 2013 among group
      C(trend:P < 0.01). The prevalence rate of syphilis decreased from 13.2% in 2010
      to 9.5% in 2013 among group A, from 6.1% in 2010 to 5.7% in 2013 among group B,
      from 8.7% in 2010 to 6.2% in 2013 among group C (trend:P < 0.01). In this MSM
      population, 77.1% of them were at age 21-40, 9.4% were at age 41-50 and 2.8% were
      older than 50 years of age. Both the prevalence rates of HIV and syphilis were
      the highest-10.1% and 13.6%, among age group of over 50s, respectively.
      CONCLUSION: HIV prevalence among MSM increased rapidly in the last four years,
      especially in older age groups and from public bathrooms. More intervention
      efforts should be targeting on MSM with the above mentioned characters.

PMID- 25059365
TI  - [Forecast the trend of burden from fatal road traffic injuries between 2015 and
      2030 in China].
AB  - OBJECTIVE: To predict the burden caused by fatal road traffic injuries from 2015
      to 2030. METHODS: We searched the websites of United Nations Population
      Division,United States Department of Agriculture, World Health Organization,
      China Energy Research Foundation and other agencies to obtain the predictive
      values of gross domestic product (GDP) per capita, urbanization, motorization and
      education from 2015 to 2030 in China. Predicted values were then applied to log
      linear models to estimate the numbers and years of life lost due to road traffic
      injuries from 2015 to 2030. RESULTS: The mortality rate caused by road traffic
      injury decreased slightly, from 13.7/100 000 in 2015 to 11.8/100 000 in 2030.
      191, 189, 183, 169 thousand persons were estimated to die from road traffic
      crashes in 2015, 2020, 2025 and 2030, respectively, showing a declining trend.
      Years of Life Lost (YLLs) caused by road traffic deaths were predicted to be 6
      918, 6 634, 6 189, 5 513 thousand years in 2015, 2020, 2025 and 2030,
      respectively, also showing a gradual downward trend. But the YLLs displayed an
      increase among people at 55 years of age or older, between 2015 and 2030. Results
      from the sensitivity analysis showed a stable forecasting result. CONCLUSION:
      Mortality, number of deaths and YLLs from road traffic crashes were predicted to
      decrease slightly, between 2015 and 2030 but the number of deaths and YLLs due to
      road traffic injuries will continue to increase from 2015 to 2030.

PMID- 25059366
TI  - [Evaluation on the effects of prevention and control programs regarding typhoid
      fever and paratyphoid fever in Guizhou province, from 2007 to 2012].
AB  - OBJECTIVE: This study was to evaluate the effects of prevention and control
      regarding programs on typhoid fever and paratyphoid fever, in Guizhou province,
      from 2007 to 2012, to provide evidence for the improvement of related programs.
      METHODS: Data on typhoid fever and paratyphoid including information on
      epidemics, individual, cases, measures for prevention and control programs taken
      and relative government documents were collected and analyzed in Guizhou
      province, from 2007 to 2012. Information related to the average annual incidence,
      nature of outbreaks, time span before confirmed diagnosis was made, unit which
      carried the case report, proportion of laboratory confirmed diagnosed cases and
      case-management were compared between 2007-2009 and 2010-2012 descriptively while
      chi-square test with Excel and EpiInfo software were used for data analysis.
      RESULTS: In the period of 2007-2009, a total of 5 978 typhoid fever and
      paratyphoid fever cases were reported in Guizhou province with the average yearly
      incidence as 5.29/100 000. In the period of 2010-2012, 2 765 cases were reported
      with the average yearly incidence as 2.57/100 000. When compared to the former,
      data from the latter period showed that the average yearly incidence had declined
      51.31% in all the prefectures. There were still some outbreaks appeared but the
      total number of cases involved reduced 87.50%. The time span before the
      confirmation of diagnosis became shorter but the difference was not statistically
      significant (chi2 = 0.08, P = 0.99). Number of cases reported by hospitals at
      county or above had 11.51% of increase while those cases reported at the township
      hospitals or below decreased for 61.47% . The proportion of laboratory diagnosed
      cases increased 23.63%. Rates of timeliness on cards being filled in, input and
      audited showed increase of 8.44%, 6.76% and 2.40% respectively. CONCLUSION:
      Successful measures for prevention and control on typhoid fever and paratyphoid
      fever had been remarkably taken in Guizhou province, but the potential risk of
      outbreaks still existed in some areas, suggesting that health education and
      surveillance programs including laboratory diagnosis, should be strengthened.

PMID- 25059367
TI  - [Association between body mass index and quality of life in Chinese adults].
AB  - OBJECTIVE: To assess the relationship between body mass index and quality of life
      (QOL) in Chinese adults. METHODS: 83 347 subjects from database of 2010 Chronic
      Non-communicable Disease and Risk Factor Surveillance in China were included in
      this study. Questionnaire was used to collect general information and health
      status. WHO QOL-BREF was adopted as an instrument to measure the quality of life
      among all the subjects. Weight and height of each subject were measured, and then
      body mass index (BMI) was calculated. Kruskal-Wallis test was used to compare QOL
      from different BMI classifications. Multiple logistic regression analysis was
      used to assess the association of QOL with BMI in different sex. RESULTS: Among
      83 347 subjects, when compared with normal weight adults, their QOL scores were
      relatively low for those underweight, overweight and obese adults. Scores of
      psychological and environment domains in the overweight adult groups were higher
      than other groups. The highest score of social relationship domain was for obese
      group and the lowest score was seen in the underweight group. Differences on the
      above said groups were significant (P < 0.000 1). When compared to normal weight
      adults, after adjusting for other factors, OR impaired QOLs in physical (OR =
      1.38, 95% CI:1.12-1.70), mental (OR = 1.29, 95% CI:1.08-1.54), social
      relationship and (OR = 1.26, 95% CI:1.08-1.47) and environment domains (OR =
      1.37, 95% CI:1.12-1.67) all increased among men in the underweight group.
      However, ORs of impaired QOL in physical (OR = 0.88, 95%CI:0.82-0.94; OR = 0.90,
      95%CI: 0.82-0.98), psychological (OR = 0.88, 95% CI:0.83-0.94; OR = 0.83, 95%
      CI:0.77-0.90), social relationship (OR = 0.89, 95%CI:0.84-0.94; OR = 0.78,
      95%CI:0.71-0.85) and environment domains (OR = 0.85, 95%CI:0.80-0.92; OR = 0.79,
      95%CI:0.73-0.86) decreased among both overweight and obese men, respectively. For
      women,ORs of impaired QOL in social relationship (OR = 0.92, 95%CI: 0.85-0.98)
      and environment domains (OR = 0.91, 95%CI:0.80-0.92) both decreased in the
      overweight group. And the ORs decreased also in impaired QOL in social
      relationship domain (OR = 0.86, 95%CI: 0.78-0.95) for obese women. CONCLUSION:
      QOLs of the four domains were different for adults with different BMl
      classification. Underweight men showed poor QOL on these four domains while
      overweight and obese men had better QOLs. For women, overweight group had better
      QOLs in both relationship and environment domains but obese women had better
      relationship QOL.

PMID- 25059368
TI  - [Epidemiological study on the trend of accidental deaths among children under
      five in Beijing, during 2003-2012].
AB  - OBJECTIVE: To study the trend of accidental death among children under 5 years of
      age in Beijing. METHODS: Cases of death in children under 5 years old in Beijing,
      during 2003-2012 were collected, to analyze the strength and trends of accidental
      death, main causes of accident and its epidemiological features. RESULTS: The
      overall accidental death was 8.47% of all death among children under 5 years old
      in Beijing during 2003-2012. During these 10 years, data showed a downward trend
      on the mortality rates on injuries (P < 0.05), especially on drowning, in 1-4
      year old and rural children under five years of age. In 2012, the accidental
      death rate of children under five was 6.37/105. The 5 main causes of accidental
      deaths were suffocation, traffic accident, falling, poisoning and drowning, in
      order of size. The main causes of death were suffocation in the 0-1 year group,
      suffocation and traffic accident in the 1-2 year group and traffic accident in
      the 3-4 year group. The proportion of deaths due to traffic accident increased
      gradually with age. Area distribution showed that accidental deaths mainly
      happened in rural area (52.19%), with two main types as traffic accident and
      suffocation. CONCLUSION: The reduction of accidental death rate among children
      under 5 years old in Beijing mainly was caused by the decline of accident
      mortality in 1-4 year old and children in the rural areas. Our data suggested
      that the focus in reducing the accidental death rate among children under 5 years
      old in Beijing should target on the prevention of infant suffocation and traffic
      accidents among the 1-4 year old, with rural areas in particular.

PMID- 25059369
TI  - [An investigation on surgical-site infection among post cesarean section patients
      with Burkholderia cepacia contaminated ultrasonic couplant].
AB  - OBJECTIVE: In May 2013, an abnormal increase of surgical-site infection among
      post cesarean section patients was reported at one hospital in Zhongshan. An
      investigation was conducted to identify the risk factors and related control
      measures. METHODS: All the reported surgical-site infection records among post
      cesarean section patients were checked. A review of cesarean section schedules of
      health workers was also performed. An 1 : 2 case-control study was conducted
      among surgical-site infection cases in May 2013. Microbiologic cultures were
      performed on 2 surgical site secretion samples and 12 samples from the
      environment. All the positive isolates were molecular typed by pulsed field gel
      electrophoresis (PFGE). RESULTS: In May 2013, 4 post cesarean section patients
      who developed surgical-site infection symptom at one hospital in Zhongshan were
      reported, with an attack rate as 10.3% (4/39). The emergence time of symptom was
      2-3 days after operation. All of the 4 cases underwent an emergency operation.
      The median time interval for cases from admission to operation was 7.2 hours
      (ranged from 2 to 9 hours), lower than that seen in the controls, with a median
      time of 20.8 hours (Z = 5.50, P = 0.03). Two of the 4 cases took type-B
      ultrasonic inspection 1.4 h and 8.4 h before the operation, and the other two
      cases took continuous fetal heart monitoring 2 hours before the operation. Skin
      of the operation area on the 4 cases had been exposed to ultrasonic couplant,
      without a thorough clean. The proportion of type-B ultrasonic inspection or
      continuous fetal heart monitoring was much higher in cases than in controls (chi2
      = 5.19, P = 0.01). Burkholderia cepacia (BC) isolates were discovered from:one
      surgical site secretion, 2 type-B ultrasonic probe samples, one ultrasonic
      couplant in use and one ultrasonic couplant unopened. All the isolates were
      identified as 100% identical by PFGE. CONCLUSION: The skin of operation area of
      cesarean section patients had been exposed to BC contaminated ultrasonic couplant
      without thorough cleaning, which seemed to be related to the outbreak of surgical
      site infection, in our case.

PMID- 25059370
TI  - [Influence of folate on fragile histidine triad gene expression, cell
      proliferation and apoptosis in cervical cancer cell lines].
AB  - OBJECTIVE: To explore the effect of folate on cell proliferation and apoptosis as
      well as on DNA methylation, expression of mRNA and protein of fragile histidine
      triad (FHIT)gene in cervical cancer cells. METHODS: Cervical cancer cell lines
      including CaSki (HPV16-positive) and C33A (HPV-negative)were cultured in vitro
      with different folate concentrations. Cell proliferation and apoptosis were
      determined by viable cell counting and flow cytometry while FHIT gene DNA
      methylation was used with methylation specific PCR (MSP). Both gene expression of
      FHIT protein and mRNA were detected by Western blot and Real-time PCR,
      respectively. RESULTS: Folate could inhibit the proliferation and promote the
      apoptosis in two kinds of cervical cancer cells. The number of viable cells
      decreased (C33A:r = 0.98, P < 0.001; CaSki:r = 0.98, P < 0.001) and the apoptosis
      rate increased (C33A:r = 0.98, P < 0.001; CaSki:r = 0.99, P < 0.001) along with
      the increase of folate concentration. FHIT gene DNA methylation showed all
      positive at the folate concentration levels of 1 ug/ml and 10 ug/ml, partially
      positive at 100 ug/ml and 250 ug/ml, but negative at 500 ug/ml and 1 000 ug/ml in
      both C33A and CaSki cells. Comparing with the control group, the mRNA or protein
      relative expression levels of FHIT gene in different folate concentrations were
      statistically significant in two kinds of cells, and showing that the FHIT gene
      mRNA expression (C33A:r = 0.96, P < 0.001; CaSki:r = 0.94, P < 0.001) and protein
      expression (C33A:r = 0.96, P < 0.001; CaSki:r = 0.97, P < 0.001) both increased
      along with the increase of folate concentration. CONCLUSION: Our findings
      indicated that adequate folate seemed to be able to effectively inhibit the
      proliferation of cervical cancer cells and facilitate their apoptosis in vitro,
      so would reverse the aberration mRNA and protein expression of FHIT gene.

PMID- 25059371
TI  - [Phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains identified
      in China].
AB  - OBJECTIVE: To understand the phenotypic diversity of toxigenic Vibrio cholerae O1
      El Tor strains isolated from different provinces in China during the last 50
      years. METHODS: Traditional biotyping testings including susceptibility to
      polymyxin B, sensitivity to group IV phage, Voges-Proskauer test and haemolysis
      of sheep erythrocytes were conducted. RESULTS: Data from Biotype-specific
      phenotype analysis revealed that only 133 isolates carried the typical El Tor
      phenotypes while the other 251 isolates displayed atypical El Tor phenotypes.
      Combined with ctxB, rstR genotypes and phenotypic characteristics, 64 isolates
      were identified as typical El Tor biotype, 21 were El Tor variants that showing
      the typical El Tor biotype-specific phenotype but with ctxB(class). 280 isolates
      were defined as the hybrid groups with traits of both classical and El Tor
      biotypes that could be further classified into 45 groups, based on the
      combination of genotypes of ctxB, rstR and phenotypic characteristics.
      CONCLUSION: Toxigenic Vibrio cholerae O1 El Tor strains that isolated from
      different provinces in China displayed high phenotypic diversity. The traditional
      biotype traits could not be used to correctly distinguish the two different
      biotypes.

PMID- 25059372
TI  - [Using the real-time PCR assay to establish TaqMan-MGB probe for rapid
      identification of Clostridium difficile and its toxin].
AB  - OBJECTIVE: To develop a real-time PCR assay for the rapid identification of
      Clostridium(C.)difficile and its toxin. METHODS: TaqMan real-time PCR was
      developed for the rapid identification of species specific gene(tpi) of C.
      difficile strains and the toxins A(TcdA), B(TcdB) and truncated toxin A(TcdAT).
      Sensitivity, specificity and anti-interference ability of these methods were
      estimated, as well. Feces sampled from fifty diarrhea patients were tested by
      real-time PCR and compared to the results from VIDAS assay. RESULTS: The
      detection limits of tpi were 6*10-2 CFU/ul and 6 * 10-1 CFU/ul in the non-oxin
      producing and toxin producing strains, respectively. The coefficients of
      variability(CV) of intra-assay and inter-assay for the detection limits of tpi in
      the non-toxin producing strain were 2.1% and 2.3% . The CVs of intra-assay and
      inter-assay for the detection limit of tpi, tcdA, tcdB and tcdAT in the toxin
      producing strain were 3.0% and 3.4%, 2.9% and 3.2%, 5.3% and 5.7%, 2.7% and 2.8%,
      respectively. No interference was detected from other genus or species in
      clostridium. From 50 clinical samples, thirty-nine of them were negative and six
      of them were positive under the TaqMan-MGB probe technique in accordance with
      VIDAS. Five samples appeared positive using the TaqMan-MGB probe technique, in
      which 3 were dubious and 2 were negative under VIDAS. CONCLUSION: The newly
      developed method was a sensitive and reliable assay for rapid identification of
      C. difficile and its toxin. This method could be used to screen C. difficile
      isolates harboring truncated toxin A to avoid misdiagnosis, clinically.

PMID- 25059373
TI  - [Clustered regularly interspaced short palindromic repeat associated protein
      genes cas1 and cas2 in Shigella].
AB  - OBJECTIVE: To detect the distribution of clustered regularly interspaced short
      palindromic repeat (CRISPR) associated protein genes cas1 and cas2 in Shigella
      and to understand the characteristics of CRISPR with relationship between CRISPR
      and related characteristics on drug resistance. METHODS: CRISPR associated
      protein genes cas1 and cas2 in Shigella were detected by PCR, with its products
      sequenced and compared. RESULTS: The CRISPR-associated protein genes cas1 and
      cas2 were found in all the 196 Shigella isolates which were isolated at different
      times and locations in China. Consistencies showed through related sequencing
      appeared as follows: cas2, cas1 (a) and cas1 (b) were 96.44%, 97.61% and 96.97%,
      respectively. There were two mutations including 3177129 site(C->G)and 3177126
      site (G->C) of cas1 (b) gene in 2003135 strain which were not found in the
      corresponding sites of Z23 and 2008113. RESULTS: showed that in terms of both
      susceptibility and antibiotic-resistance, strain 2003135 was stronger than Z23
      and 2008113. CONCLUSION: CRISPR system widely existed in Shigella, with the level
      of drug resistance in cas1 (b) gene mutant strains higher than in wild strains.
      Cas1 (b) gene mutation might be one of the reasons causing the different levels
      of resistance.

PMID- 25059374
TI  - [Multispacer typing of Chinese Anaplasma phagocytophilum isolates].
AB  - OBJECTIVE: To type the Chinese Anaplasma phagocytophilum isolates by Multispacer
      typing (MST). METHODS: Based on the genomes of the 4 published Anaplasma strains,
      4 genomic sequences were analyzed by Mauve 2.3.1 software and variable spacer
      sequences were selected for designing primers with the bio-software Primer
      Premier 5.0. A total of 11 Chinese A. phagocytophilum isolates, obtained from
      different areas of China during 2009-2012 were assayed by the MST. Twenty two
      intergenic sequences for each isolate tested and the reference A. phagocytophilum
      strain Webster and A. phagocytophilum strain HZ were concatenated in the order of
      HGA-mst 1F/1R-mst 2F/2R, HGA-mst 22F/22R. RESULTS: Twenty two pairs of primers
      were successfully used for typing the Human granulocytic anaplasmosis (HGA)
      strains in the study. Those 22 intergenic sequences exhibited a great diversity
      among the strains tested and each of the strain tested was identified as unique
      genotype, according to the alignment analysis of the 22 concatenated intergenic
      sequences. Of these single nucleotide polymorphism (SNPs) identified in the
      study, the nucleotide transitions shared the highest percentage (60.2%, 251/417)
      and then the nucleotide transversion, accounted for 23.0% (96/417) and the indel
      events (insertion/deletion) were observed of 16.7% (70/417)SNPs. Phylogenetic
      analysis indicated that the 5 strains from patients (LZ-H1, LZ-H2, LZ-H3, LZ-H4,
      LZ-H5) from Laizhou areas, Shandong province and 1 tick strain (LZ-T1) from
      Haemaphysalis longicornis collected from the same areas where the patients lived
      were grouped in the same clan with the reference A. phagocytophilum strain
      Webster and strain HZ. Beijing isolates (BJ-H1) grouped with Xinjiang isolates
      (XJ-H1 and XJ-H3) while another tick isolates from Laizhou areas (LZ-T2) and
      another Xinjiang human isolate(XJ-H2)were in the same clan, which was closely
      related to the isolates from severe patients in Laizhou. CONCLUSION: Chinese HGA
      isolates exhibited a great diversity of intergenic regions. MST seemed a valuable
      tool for the detection and tracing for any endemic strains of Anaplasma during
      the outbreak investigations in the public health events.

PMID- 25059375
TI  - [Association between polymorphism of ATP2B1 gene, its interaction with smoking
      and essential hypertension -a case-control study].
AB  - OBJECTIVE: To investigate the association between polymorphism of ATP2B1 gene,
      its interaction with smoking and susceptibility of essential hypertension.
      METHODS: A case-control study was conducted to elucidate the role of ATP2B1 gene
      variants related to the risk of essential hypertension. Genomic DNA was extracted
      from peripheral blood leukocytes, using the QIAamp DNA Mini Kit (QIAGEN,Germany).
      Two SNPs, - rs17249754 and rs6253, were examined on 1 280 patients and 1 010
      healthy controls, using a Snapshot method. Statistical analyses were performed
      with SPSS Windows software (version 19.0;SPSS, Chicago, IL). RESULTS: A
      significant difference was found in rs17249754 allele frequency between cases and
      controls (OR = 1.223, 95%CI: 1.083-1.381, P = 0.001). After adjustment for age,
      sex, BMI, smoking and drinking, the difference was still statistically
      significant (OR = 1.212, 95%CI:1.070-1.373, P = 0.003). In addition, data from
      genotype distribution analysis under different models showed that appeared
      significant associations between ATP2B1 gene polymorphism and essential
      hypertension (additive model OR = 1.469, 95%CI: 1.121-1.925, P = 0.005; dominant
      model OR = 1.324, 95%CI:1.029-1.704, P = 0.029;recessive model OR = 1.123,
      95%CI:1.031-1.223, P = 0.008). In this study, the proportion of smokers in cases
      was significantly higher than that in controls (P = 0.005), but no associations
      between rs17249754-smoking interaction and essential hypertension were found
      after the adjustment for gender, age, BMI and alcohol consumption (OR = 1.024,
      95% CI:0.614-1.707). CONCLUSION: Our research findings showed that the
      polymorphism of ATP2B1 gene rs17249754 was significantly associated with the
      incidence of essential hypertension in Han population of northeastern China.
      However, the interaction between rs17249754 and smoking did not seem to have
      contributed to the occurrence of the essential hypertension.

PMID- 25059376
TI  - [Association between the glomerular filtration rate of renal dysfunction and
      metabolic syndrome: an age-stratified analysis].
AB  - OBJECTIVE: To explore the relationship between the renal dysfunction rate and
      metabolic syndrome(MS), stratified by age. METHODS: People took part in physical
      check-up in a certain tertiary hospital from March 2010 to September 2012, were
      enrolled in this study. Estimated glomerular filtration rate (eGFR), -a renal
      dysfunction indicator, was calculated by modified MDRD equation [<60 ml/min(1.73
      m(2))]. Associations between the renal dysfunction rate and factors as age,
      gender and MS traits, were assessed by stratified analysis. RESULTS: Eligible
      data from 75 469 subjects were used. The prevalence rates of renal dysfunctions
      appeared to be 0.05%,0.20%, 1.68% in 18 to 44 year-olds (youth), 45 to 59 year
      olds (middle) and 60 year-olds or above (old), respectively. Participants with MS
      showed a significantly higher risk than those without, in the elderly only (P <
      0.05)but not in the other 2 groups (P > 0.05). Participants with 2 components of
      MS in middle-aged, 3 or 5 components of MS in the elderly showed a significantly
      high incidence (P < 0.05), but no significant differences seen in other subgroups
      (P > 0.05). Increasing trend was not seen in all the 3 groups (P > 0.05).
      Elevated blood pressure (BP+) in youth and middle-aged groups, decreased high
      density lipoprotein (HDL-C) in middle-aged and elderly groups and elevated
      fasting plasma glucose (FPG+) in elderly group could all cause the abnormality
      rate of eGFR which showed significantly high incidence rates in the subgroup
      analysis (P < 0.05). The maximum of population attributable risk proportion
      (PAR%) was 41.91% in youth when having elevated BP. Relationship between renal
      dysfunction rate and triglyceride (TG)/obesity was not identified. CONCLUSION:
      The prevalence of renal dysfunction was found low, in Xuzhou. The incidence was
      not associated with the numbers but might relate to the nature of certain
      components of MS. Increased BP showed both short-term and mid-term effects.
      Decreased HDL-C, however, indicated both mid-term and long-term effects. The
      elevated FPG only appeared long-term effects. Increased TG and obesity did not
      show significant effects in these observed samples. PAR% of increased BP seemed
      to be the most important factors which might lead to renal dysfunction.

PMID- 25059377
TI  - [Correlation between urinary stones and urinary tract infections].
AB  - OBJECTIVE: To explore the correlation of urinary stones and urinary tract
      infections. METHODS: 300 cases with urinary tract stones received in our hospital
      from Feb. 2010 to Oct. 2013 were chosen as study samples. Urine routine index,
      situation of urine positivity and urinary tract infection after surgery were
      analyzed while, intraoperative cotton swabs were tested after being dipped in
      liquid near stones. Main components of stones in non-infected and infected stone
      group were analyzed and compared. Data on urolithiasis was collected. RESULTS: 96
      infected stones were found in 300 patients, accounting for 32%, which including
      35 cases of E. coli (36.5%), 28 cases of Staphylococcus epidermidis (29.2%), and
      15 cases of Proteus mirabilis (15.6%). Numbers of urine abnormalities, urine
      positivities, positive intraoperative cotton swabs and urinary tract infections
      in patients in the group with infected stones, were significantly higher than in
      the group without infected stones and the differences were statistically
      significant (chi2 = 8.203, 73.99, 178.9, 24.26, P < 0.05). The incidence rates of
      hexahydrate magnesium ammonium phosphate, carbonate apatite and hydroxyapatite
      stones in the group with infected stones were significantly higher than those in
      the non-infected-rock group while the incidence rates of calcium oxalate and uric
      acid stones were found significantly lower than those in the non-infected-stone
      group, with differences statistically significant (chi2 = 167.6, 21.00, 8.586,
      73.17, 48.79, P < 0.05). CONCLUSION: Bacteria could cause urinary tract stones,
      and infected stones were always associated with urinary tract infections.
      Bacteria detection in patients with urinary calculi was particularly important to
      avoid the urinary tract infections.

PMID- 25059378
TI  - [Estimation and application of case fatality rate, using the summarizing data].
AB  - To evaluate five methods in the estimation on the rate of case fatality during
      the epidemics of diseases based on the summarizing data. Case fatality rates,
      derived from the simulation data, 2003 SARS epidemic data in Hong Kong, Singapore
      Beijing and the 2013 H7N9 epidemic data in mainland China were analyzed, using
      these 5 methods. Results from the simulation analysis discovered that the
      relative errors and the standard deviations of the Chen [7, 8] (method 3), Chen
      [9] (method 4)were minor with high accuracy. Data from the analysis on 2003 SARS
      epidemic was noticed that the estimation from method 3, 4 in Hong Kong and
      Singapore both showing high veracities. Since the case fatality rate reported in
      Beijing was not a constant value, method 5 showed low accuracy even though it was
      close to the final case fatality rate. Data from the 2013 H7N9 epidemic showed
      that the estimations of method 1, 2, 3, 4 were all higher than that in the method
      5, suggesting that method 3, 4 could be used to estimate the case fatality rates
      of epidemics more precisely. 

PMID- 25059379
TI  - [A review on the application of Markov model in AIDS research].

PMID- 25059380
TI  - [Application of metabolomics in research on cardiovascular disease].

PMID- 25059381
TI  - In vitro evaluation of some parameters involved in mucoadhesion of aqueous
      polymeric dispersions.
AB  - Abstract Context: The mucoadhesive formulations are constantly developing due to
      their relevance in the drug delivery to various districts of the organism.
      Objective: The purpose of this study was to find a direct link between
      physicochemical properties of the polymers and their adhesive ability in order to
      offer guidelines for the development of mucoadhesive semisolid formulations.
      Materials and methods: Twelve polymers were dispersed in water and characterized
      with regard to their mucoadhesiveness, apparent viscosity, contact angle on solid
      surface, and hydrodynamic diameter of their molecules. The adhesive properties
      were related to the other measured parameters. Results and discussion: The data
      seem to indicate the existence of an optimal value of viscosity, around 5-6 Pa s,
      to obtain the highest mucoadhesiveness of the polymeric dispersions. Regarding
      the molecular sizes, the best mucoadhesive performances seem to be given from
      polymers with a hydrodynamic diameter lower than 350-400 nm. In any case, the
      ability to wet the surface by the polymeric dispersion seems to play an essential
      role in bioadhesion process, capable of strongly limiting the phenomenon.
      Conclusions: Performing simple in vitro measurements, it seems possible to
      identify the best polymeric concentration to obtain a semisolid formulation with
      good mucoadhesive properties.

PMID- 25059382
TI  - Application of Capmul MCM and caprylic acid for the development of danazol-loaded
      SEDDS.
AB  - Abstract The feasibility of using Capmul MCM and caprylic acid (medium-chain
      triglyceride pre-digestion products) as the lipid phase was investigated for the
      development of self-emulsifying drug delivery system (SEDDS) as a carrier system
      to enhance solubilization of poorly water-soluble danazol. The composition of
      SEDDS was first evaluated by phase diagrams of lipid/surfactant/water systems.
      Thereafter, danazol-loaded SEDDS was formulated and subjected to
      dispersion/precipitation study in distilled water, HCl buffer, phosphate buffer,
      or biorelevant aqueous media. The mechanism of danazol dispersion was
      investigated by comparing the solubilization capacity of blank SEDDS dispersed in
      various aqueous media with respective dispersion/precipitation profiles obtained.
      Phase diagrams showed that at least 30% (w/w) Cremophor RH40, as the surfactant,
      was needed to properly emulsify Capmul MCM:caprylic acid (1:1), as the lipid
      phase. Different extent of danazol precipitation was observed upon the dispersion
      of danazol-loaded SEDDS in different aqueous media. Danazol precipitation was
      dominated by the solubilization capacity of danazol, which was influenced by the
      ratio of Capmul MCM:CA and Cremophor RH40, pH of aqueous media, gastrointestinal
      composition, and blank SEDDS concentration.

PMID- 25059383
TI  - The chloroplast view of the evolution of polyploid wheat.
AB  - Polyploid wheats comprise four species: Triticum turgidum (AABB genomes) and T.
      aestivum (AABBDD) in the Emmer lineage, and T. timopheevii (AAGG) and T.
      zhukovskyi (AAGGA(m) A(m) ) in the Timopheevi lineage. Genetic relationships
      between chloroplast genomes were studied to trace the evolutionary history of the
      species. Twenty-five chloroplast genomes were sequenced, and 1127 plant
      accessions were genotyped, representing 13 Triticum and Aegilops species. The A.
      speltoides (SS genome) diverged before the divergence of T. urartu (AA), A.
      tauschii (DD) and the Aegilops species of the Sitopsis section. Aegilops
      speltoides forms a monophyletic clade with the polyploid Emmer and Timopheevi
      wheats, which originated within the last 0.7 and 0.4 Myr, respectively. The
      geographic distribution of chloroplast haplotypes of the wild tetraploid wheats
      and A. speltoides illustrates the possible geographic origin of the Emmer lineage
      in the southern Levant and the Timopheevi lineage in northern Iraq. Aegilops
      speltoides is the closest relative of the diploid donor of the chloroplast
      (cytoplasm), as well as the B and G genomes to Timopheevi and Emmer lineages.
      Chloroplast haplotypes were often shared by species or subspecies within major
      lineages and between the lineages, indicating the contribution of introgression
      to the evolution and domestication of polyploid wheats.

PMID- 25059384
TI  - Self-report pain and symptom measures for primary dysmenorrhoea: a critical
      review.
AB  - Primary dysmenorrhoea (PD) is highly prevalent among women of reproductive age
      and it can have significant short- and long-term consequences for both women and
      society as a whole. Validated symptom measures are fundamental for researchers to
      understand women's symptom experience of PD and to test symptom interventions.
      The objective of this paper was to critically review the content and psychometric
      properties of self-report tools to measure symptoms of PD. Databases including
      PubMed, PsychoINFO, Cumulative Index of Nursing and Allied Health Literature, and
      Health and Psychosocial Instruments were searched for self-report symptom
      measures that had been used among women with either PD or perimenstrual symptoms.
      A total of 15 measures met inclusion criteria and were included in the final
      analysis. The measures were categorized into generic pain measures, dysmenorrhoea
      specific measures, and tools designed to measure perimenstrual symptoms. These
      measures had varying degrees of comprehensiveness of symptoms being measured,
      relevance to PD, multidimensionality and psychometric soundness. No single
      measure was found to be optimal for use, but some dysmenorrhoea-specific measures
      could be recommended if revised and further tested. Key issues in symptom
      measurement for PD are discussed. Future research needs to strengthen
      dysmenorrhoea-specific symptom measures by including a comprehensive list of
      symptoms based on the pathogenesis of PD, exploring relevant symptom dimensions
      beyond symptom severity (e.g., frequency, duration, symptom distress), and
      testing psychometric properties of the adapted tools using sound methodology and
      diverse samples. 

PMID- 25059385
TI  - Telocytes in mice bone marrow: electron microscope evidence.
AB  - Telocytes (TCs) are a novel type of interstitial cell of whom presence has been
      recently documented in many tissues and organs. However, whether TCs exists in
      bone marrow is still not reported. This study aims to find out TCs in mice bone
      marrow by using scanning electron microscope (SEM) and transmission electron
      microscope (TEM). SEM images showed that in mice bone marrow most of TCs have
      small spherical cell body (usually 4-6 MUm diameter) with thin long telopodes
      (Tps; usually one to three). The longest Tp observed was about 70 MUm, with an
      uneven calibre. Direct intercellular contacts exist between TCs. TEM shows
      mitochondria within dilations of Tps. Also, by TEM, we show the close spatial
      relations of Tps with blood vessels. In conclusion, this study provides
      ultrastructural evidence regarding the existence of TCs in mice bone marrow, in
      situ. 

PMID- 25059387
TI  - Sox4 up-regulates Cyr61 expression in colon cancer cells.
AB  - BACKGROUND/AIMS: Genetic changes leading to aberrant activation of oncogenes are
      viewed as a crucial step in colon cancer. Sox4, a member of Sox (Sry-box) family
      of transcription factors, plays a critical role in tumorigenesis. METHODS: PCR
      based microarrays were used to identify potential transcriptional target of Sox4.
      siRNA was used to knockdown the expression of Sox4. Luciferase and chromatin
      immunoprecipitation (ChIP) assays were used to test the transcriptional
      regulations. RESULTS: PCR-based microarrays found that Cyr61, a secreted
      extracellular matrix-associated signaling protein, was a transcriptional target
      of Sox4. Overexpression of Sox4 increased, while its knockdown using small
      interfering RNA (siRNA) reduced Cyr61 expression. A potential Sox4 binding motif
      located at the proximal Cyr61 promoter was identified. CONCLUSION: Thus, our
      results suggest a previously unknown Sox4-Cyr61 molecular network, which may
      control colon cancer cell proliferation and survival.

PMID- 25059386
TI  - Protein profiling of human lung telocytes and microvascular endothelial cells
      using iTRAQ quantitative proteomics.
AB  - Telocytes (TCs) are described as a particular type of cells of the interstitial
      space (www.telocytes.com). Their main characteristics are the very long telopodes
      with alternating podoms and podomers. Recently, we performed a comparative
      proteomic analysis of human lung TCs with fibroblasts, demonstrating that TCs are
      clearly a distinct cell type. Therefore, the present study aims to reinforce this
      idea by comparing lung TCs with endothelial cells (ECs), since TCs and ECs share
      immunopositivity for CD34. We applied isobaric tag for relative and absolute
      quantification (iTRAQ) combined with automated 2-D nano-ESI LC-MS/MS to analyse
      proteins extracted from TCs and ECs in primary cell cultures. In total, 1609
      proteins were identified in cell cultures. 98 proteins (the 5th day), and 82
      proteins (10th day) were confidently quantified (screened by two-sample t-test, P
      < 0.05) as up- or down-regulated (fold change >2). We found that in TCs there are
      38 up-regulated proteins at the 5th day and 26 up-regulated proteins at the 10th
      day. Bioinformatics analysis using Panther revealed that the 38 proteins
      associated with TCs represented cellular functions such as intercellular
      communication (via vesicle mediated transport) and structure morphogenesis, being
      mainly cytoskeletal proteins and oxidoreductases. In addition, we found 60 up
      regulated proteins in ECs e.g.: cell surface glycoprotein MUC18 (15.54-fold) and
      von Willebrand factor (5.74-fold). The 26 up-regulated proteins in TCs at 10th
      day, were also analysed and confirmed the same major cellular functions, while
      the 56 down-regulated proteins confirmed again their specificity for ECs. In
      conclusion, we report here the first extensive comparison of proteins from TCs
      and ECs using a quantitative proteomics approach. Our data show that TCs are
      completely different from ECs. Protein expression profile showed that TCs play
      specific roles in intercellular communication and intercellular signalling.
      Moreover, they might inhibit the oxidative stress and cellular ageing and may
      have pro-proliferative effects through the inhibition of apoptosis. The group of
      proteins identified in this study needs to be explored further for the role in
      pathogenesis of lung disease. 

PMID- 25059388
TI  - The proteomics of pediatric brain tumors.
AB  - Pediatric tumors of the CNS are the leading cause of cancer-related mortality in
      children. In pediatric pathology, brain tumors constitute the most frequent solid
      malignancy. An unparalleled outburst of information in pediatric neuro-oncology
      research has been witnessed over the last few years, largely due to increased use
      of high-throughput technologies such as genomics, proteomics and meta-analysis
      tools. Input from these technologies gives scientists the advantage of early
      prognosis assessment, more accurate diagnosis and prospective curative intent in
      the pediatric brain tumor clinical setting. The present review aims to summarize
      current knowledge on research applying proteomics techniques or proteomics-based
      approaches performed on pediatric brain tumors. Proteins that can be used as
      potential disease markers or molecular targets, and their biological
      significance, are herein listed and discussed. Furthermore, future perspectives
      that proteomics technologies may offer regarding this devastating disorder are
      presented. 

PMID- 25059389
TI  - Highly efficient photocatalytic hydrogen evolution by nickel phosphide
      nanoparticles from aqueous solution.
AB  - Monodispersed nickel phosphide (Ni2P) nanoparticles were for the first time
      applied to photocatalytic hydrogen evolution from lactic acid aqueous solution
      under visible light LED irradiation using CdS nanorods as a photosensitizer. The
      system exhibited high photocatalytic hydrogen-generating activity and excellent
      stability in aqueous acidic media. 

PMID- 25059391
TI  - Central white matter degeneration in bulbar- and limb-onset amyotrophic lateral
      sclerosis.
AB  - Previous studies using diffusion tensor imaging (DTI) have examined for
      differences between bulbar- and limb-onset amyotrophic lateral sclerosis (ALS).
      Findings between studies have been markedly inconsistent, though possibly as a
      consequence of poor matching for confounding variables. To address this problem,
      this study contrasted the DTI profiles of limb-onset (ALS-L) and bulbar-onset
      (ALS-B) in groups that were tightly matched for the potential confounding effects
      of power, age, cognitive impairment and motor dysfunction. 14 ALS-L and 14 ALS-B
      patients were selected from a large prospective study so as to be matched on
      clinical and demographic features. All subjects, including 29 controls, underwent
      neuropsychological and neurological assessment. Tract-based spatial statistics
      and region of interest techniques were used to analyse fractional anisotropy
      (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity
      (lambda1). Extensive bilateral FA and RD changes along the corticospinal tract
      were found in ALS-B compared to controls, p (corrected) <0.05; a similar
      distribution was seen for ALS-L at a less stringent statistical threshold. ROI
      analyses also showed more significant changes in ALS-B than ALS-L when each was
      compared to controls; for FA, MD and RD the changes reached statistical
      significance in the direct contrast between the two patient groups. With careful
      matching for confounding factors, the results suggest that ALS-B is associated
      with greater central white matter degeneration than ALS-L, possibly contributing
      to the known worse prognosis of ALS-B. The study, however, found no evidence that
      the spatial distribution of white matter degeneration differs between these
      groups.

PMID- 25059390
TI  - A new mutation in GJC2 associated with subclinical leukodystrophy.
AB  - Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause
      Pelizaeus-Merzbacher-like disease type 1, a severe dysmyelinating disorder. One
      recessive mutation (p.Ile33Met) has been associated with a much milder phenotype-
      hereditary spastic paraplegia type 44. Here, we present evidence that a novel
      Arg98Leu mutation causes an even milder phenotype--a subclinical leukodystrophy.
      The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild
      type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing
      Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand,
      coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such
      reductions. Single channel conductance and normalized steady-state junctional
      conductance-junctional voltage (G(j)-V(j)) relations differed only slightly from
      those for wild-type Cx47. Our data suggest that the minimal phenotype in this
      patient results from a reduced efficiency of opening of Cx47 channels between
      oligodendrocyte and oligodendrocyte with preserved coupling between
      oligodendrocyte and astrocyte, and support a partial loss of function model for
      the mild Cx47 associated disease phenotypes.

PMID- 25059392
TI  - Echocardiographic findings in patients with spontaneous CSF leak.
AB  - The presence of cardiovascular abnormalities in patients with spontaneous
      cerebrospinal fluid (CSF) leaks are not well-documented in the literature, as
      cardiovascular evaluation is not generally pursued if a patient does not exhibit
      additional clinical features suggesting an inherited connective tissue disorder.
      We aimed to assess this association, enrolling a consecutive group of 50 patients
      referred for spinal CSF leak consultation. Through echocardiographic evaluation
      and detailed medical history, we estimate that up to 20% of patients presenting
      with a spontaneous CSF leak may have some type of cardiovascular abnormality.
      Further, the increase in prevalence of aortic dilatation in our cohort was
      statistically significant in comparison to the estimated population prevalence.
      This supports a clinical basis for echocardiographic screening of these
      individuals for cardiovascular manifestations that may have otherwise gone
      unnoticed or evolved into a more severe manifestation.

PMID- 25059393
TI  - Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and
      Alzheimer's disease dementia.
AB  - Similar to Alzheimer's disease (AD), dementia with Lewy bodies (DLB) is
      characterized by a profound degeneration of cortically-projecting cholinergic
      neurons of the basal forebrain (BF) and associated depletion of cortical
      cholinergic activity. We aimed to investigate subregional atrophy of the BF in
      DLB in vivo and compare it to the pattern of BF atrophy in AD. Structural MRI
      scans of 11 patients with DLB, 11 patients with Alzheimer's disease, and 22
      healthy controls were analysed using a recently developed technique for automated
      BF morphometry based on high-dimensional image warping and cytoarchitectonic maps
      of BF cholinergic nuclei. For comparison, hippocampus volume was assessed within
      the same morphometric framework using recently published consensus criteria for
      the definition of hippocampus outlines on MRI. The DLB group demonstrated
      pronounced and subregion-specific atrophy of the BF which was comparable to BF
      atrophy in AD: volume of the nucleus basalis Meynert was significantly reduced by
      20-25%, whereas rostral BF nuclei were only marginally affected. By contrast,
      hippocampus volume was markedly less affected in DLB compared to AD. Global
      cognition as determined by MMSE score was associated with BF volume in AD, but
      not in DLB, whereas visuoperceptual function as determined by the trail making
      test was associated with BF volume in DLB, but not in AD. DLB may be
      characterized by a more selective degeneration of the cholinergic BF compared to
      AD, which may be related to the differential cognitive profiles in both
      conditions.

PMID- 25059394
TI  - Atypical late-onset hereditary spastic paraplegia with thin corpus callosum due
      to novel compound heterozygous mutations in the SPG11 gene.

PMID- 25059395
TI  - Prior medical conditions and the risk of amyotrophic lateral sclerosis.
AB  - Sporadic amyotrophic lateral sclerosis (ALS) is believed to be a complex disease
      in which multiple exogenous and genetic factors interact to cause motor neuron
      degeneration. Elucidating the association between medical conditions prior to the
      first symptoms of ALS could lend support to the theory that specific
      subpopulations are at risk of developing ALS and provide new insight into shared
      pathogenic mechanisms. We performed a population-based case-control study in the
      Netherlands, including 722 sporadic ALS patients and 2,268 age and gender matched
      controls. Data on medical conditions and use of medication were obtained through
      a structured questionnaire. Multivariate analyses showed that
      hypercholesterolemia (OR 0.76, 95% CI 0.63-0.92, P = 0.006), the use of statins
      (OR 0.45, 95% CI 0.35-0.59, P = 1.86 * 10(-9)) or immunosuppressive drugs (OR
      0.26, 95% CI 0.08-0.86, P = 0.03) were associated with a decreased risk of ALS.
      Head trauma was associated with an increased ALS susceptibility (OR 1.95, 95% CI
      1.11-3.43, P = 0.02). No association was found with autoimmune diseases, cancer,
      psychiatric disorders or cardiovascular diseases, or survival. The lower
      frequency of hypercholesterolemia and less use of statins in ALS patients
      indicate a favorable lipid profile prior to symptom onset in at least a
      subpopulation of ALS. Prior head trauma is a risk factor for ALS and the
      significantly lower use of immunosuppressive drugs in ALS patients could suggest
      a protective effect. The identification of specific subpopulations at risk for
      ALS may provide clues towards possible pathogenic mechanisms.

PMID- 25059396
TI  - Direct and indirect effects of glomalin, mycorrhizal hyphae, and roots on
      aggregate stability in rhizosphere of trifoliate orange.
AB  - To test direct and indirect effects of glomalin, mycorrhizal hyphae, and roots on
      aggregate stability, perspex pots separated by 37-MUm nylon mesh in the middle
      were used to form root-free hyphae and root/hyphae chambers, where trifoliate
      orange (Poncirus trifoliata) seedlings were colonized by Funneliformis mosseae or
      Paraglomus occultum in the root/hyphae chamber. Both fungal species induced
      significantly higher plant growth, root total length, easily-extractable glomalin
      related soil protein (EE-GRSP) and total GRSP (T-GRSP), and mean weight diameter
      (an aggregate stability indicator). The Pearson correlation showed that root
      colonization or soil hyphal length significantly positively correlated with EE
      GRSP, difficultly-extractable GRSP (DE-GRSP), T-GRSP, and water-stable aggregates
      in 2.00-4.00, 0.50-1.00, and 0.25-0.50 mm size fractions. The path analysis
      indicated that in the root/hyphae chamber, aggregate stability derived from a
      direct effect of root colonization, EE-GRSP or DE-GRSP. Meanwhile, the direct
      effect was stronger by EE-GRSP or DE-GRSP than by mycorrhizal colonization. In
      the root-free hyphae chamber, mycorrhizal-mediated aggregate stability was due to
      total effect but not direct effect of soil hyphal length, EE-GRSP and T-GRSP. Our
      results suggest that GRSP among these tested factors may be the primary
      contributor to aggregate stability in the citrus rhizosphere.

PMID- 25059398
TI  - Channelled porous TiO2 synthesized with a water-in-oil microemulsion.
AB  - Porous titanium dioxide synthesized with a bicontinuous surfactant template is a
      promising method that leads to a high active surface area electrode. The template
      used is based on a water/isooctane/dioctyl sodium sulfosuccinate salt together
      with lecithin. Several parameters were varied during the synthesis to understand
      and optimize channel formation mechanisms. The material is patterned in stacked
      conical channels, widening towards the centre of the grains. The active surface
      area increased by 116 % when the concentration of alkoxide precursors was
      decreased and increased by 241 % when the template formation temperature was
      decreased to 10  degrees C. Increasing the oil phase viscosity tends to widen the
      pore aperture, thus decreasing the overall active surface area. Changing the
      phase proportions alters the microemulsion integrity and disrupts channel
      formation. 

PMID- 25059397
TI  - Do chronic myeloid leukemia patients with late "warning" responses benefit from
      "watch and wait" or switching therapy to a second generation tyrosine kinase
      inhibitor?
AB  - In the latest recommendations for the management of chronic-phase chronic myeloid
      leukemia suboptimal responses have been reclassified as "warning responses." In
      contrast to previous recommendations current guidance advises close monitoring
      without changing therapy. We have identified 198 patients treated with first-line
      imatinib, with a warning response after 12 months of treatment (patients with a
      complete cytogenetic response but no major molecular response [MMR]). One hundred
      and forty-six patients remained on imatinib, while 52 patients changed treatment
      to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did
      not correlate with an increase in overall survival or progression-free survival.
      Nevertheless, a significant improvement was observed in the probability of a MMR:
      24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the
      probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7%
      vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to
      2GTKI remained safe; however, we have observed a 19% of treatment discontinuation
      due to side effects. We have observed an improvement of molecular responses after
      changing treatment to 2GTKI in patients with late suboptimal response treated
      with imatinib first line. However, these benefits were not correlated with an
      improvement of progression free survival or overall survival.

PMID- 25059399
TI  - Amelioration of doxorubicin-induced cardiotoxicity by resveratrol.
AB  - Doxorubicin (DOX), is a highly active anticancer agent, but its clinical use is
      limited by its severe cardiotoxic side-effects associated with increased
      oxidative stress and apoptosis. Resveratrol (RSVL) is a naturally occurring
      polyphenolic compound (trans-3,5,4'-trihydroxystilbene) found primarily in root
      extracts of the oriental plant Polygonum cuspidatum and of numerous additional
      plant species. It has recently been shown that RSVL has a number of beneficial
      effects in different biological systems, which include anti-oxidant,
      antineoplastic, anticarcinogenic, cardioprotective and antiviral effects. In this
      study, we examined whether RSVL has protective effects against DOX-induced free
      radical production and cardiotoxicity in male rats. The tested dose of DOX (20
      mg/kg) caused a significant increase in the serum activities of the cardiac
      enzymes lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) and the
      level of malondialdehyde (MDA) in the heart tissue. However, there was a
      significant decrease in the glutathione level in the heart tissue. Simultaneous
      treatment of rats with RSVL [10 mg/kg, intraperitoneal (i.p.) injection] reduced
      the activity of LDH and CPK and significantly reduced MDA production in the
      heart. The total antioxidant capacity was increased following RSVL
      administration. Electron microscopy examination of the heart tissue showed that
      DOX treatment results in massive fragmentation and lysis of the myofibrils, and
      that mitochondria show either vacuolization or complete loss of the cristae.
      Simultaneous treatment with RSVL ameliorated the effect of DOX administration on
      cardiac tissue, with cardiomyocytes appearing normal compared to the control
      samples, and mitochondria retaining their normal structure.

PMID- 25059401
TI  - The long-term effect of intravitreal ranibizumab on retinal nerve fiber layer
      thickness in exudative age-related macular degeneration.
AB  - The aim of this study was to evaluate the long-term effect of intravitreal
      ranibizumab on the retinal nerve fiber layer (RNFL) in exudative age-related
      macular degeneration (AMD). Patients with treatment naive neovascular AMD in one
      eye were enrolled into the study. Following 3 monthly intravitreal ranibizumab
      injections, the patients were evaluated according to disease activity and re
      injections were performed according to "treat and extend" protocol. During the
      follow-up, peripapillary nerve fiber layer thickness measurements were compared
      with normal fellow eyes. Forty-four eyes of 11 women and 11 men with the mean age
      of 66.3 +/- 8.8 years (50-80) were enrolled into the study. All patients had
      completed at least 12 months of follow-up time. Patients received an average of
      4.7 (3-11 injections) intravitreal injections. At baseline, no significant
      difference was observed between two groups for RNFL thickness, which was assessed
      as quadrants (p = 0.250-0.944) and globally (p = 0.814). In each group, there was
      a significant RNFL thinning (p = 0.009 and 0.022) after the third month, whereas
      no significant difference was observed between treated and untreated eyes.
      Patients were also classified according to the number of injections, and RNFL
      thickness showed no difference between eyes treated with less or more than five
      intravitreal injections (p = 0.757-0.973). Although there was no statistically
      significant difference in RNFL thickness between study and control eyes during 12
      months of follow-up, a significant thinning was recorded in both groups compared
      with baseline values. Cross-sectional images with higher resolutions and precise
      segmentation opportunities are needed to investigate the hypothesis "VEGF
      neutralization and inhibition of cell maintenance" in detail.

PMID- 25059400
TI  - Incidence of cystoid macular edema with iris-fixated posterior chamber
      intraocular lenses in patients presenting with lens dislocation.
AB  - The aim of this study is to determine the incidence of cystoid macular edema
      (CME) following repositioning and McCannel iris-suturing of dislocated
      intraocular lenses. This study is conducted in an urban private practice. A
      retrospective chart review was performed on consecutive patients who presented
      with posteriorly dislocated IOLs and underwent iris-sutured posterior chamber
      (PC) intraocular lens (IOL) placement using the McCannel suture technique by a
      single surgeon for IOL repositioning from December 2008 to August 2012. All
      charts were reviewed for etiology of dislocation, time elapsed from cataract
      surgery, best-corrected visual acuity (BCVA), slit-lamp examination, tonometry,
      and dilated fundus examination. Presence of CME was determined by spectral domain
      optical coherence tomography (Cirrus HD OCT; Carl Zeiss Meditec, Dublin,
      California, USA). Of the 58 cases reviewed, lens dislocation resulted from trauma
      in 21 %, zonular incompetence in 17 %, recent intraocular surgery in 12 %, and
      unknown in 50 %. Mean best-corrected logMAR visual acuity improved from 1.07
      preoperatively to 0.52 postoperatively (P < 0.001). The mean follow-up time was
      7.8 months. Two cases (3.4 %) of CME occurred postoperatively at a mean follow-up
      time of 4.5 months. Of these two patients, one had concurrent fragmetome
      lensectomy at the time of initial surgery. Iris-sutured PC IOL placement in this
      case series resulted in an improvement in BCVA with a low incidence of CME.

PMID- 25059402
TI  - Choroidal thickness changes in patients with pseudoexfoliation syndrome.
AB  - To evaluate the choroidal thickness using spectral-domain optical coherence
      tomography (OCT) in patients with pseudoexfoliation syndrome (PXS) and to compare
      them with healthy controls. This observational comparative study consisted of 35
      PXS patients and 35 age- and sex-matched control cases. The control cases had
      neither systemic nor ocular disease. All 70 patients underwent a complete
      ophthalmic examination as well as choroidal thickness measurement using a high
      speed and high resolution SD-OCT device (Topcon 3D OCT-2000, Japan). There was no
      significant difference with respect to mean refractive error and intraocular
      pressure measurement between patients with PXS and controls (p = 0.237 and 0.433,
      respectively). The mean choroidal thickness was found as 206.6 +/- 37.6 um in the
      PXS group and 215.9 +/- 47.3 um in controls, respectively. The mean choroidal
      thickness was not significant between the PXS patients and the control cases (p =
      0.362). Although PXS patients had lower mean choroidal thickness than controls,
      our results did not reach any statistical significance.

PMID- 25059403
TI  - The coelacanth and its genome.

PMID- 25059404
TI  - Cancer survivorship websites and resources.

PMID- 25059405
TI  - Diagnostic features of myelomeningocele: the role of ultrafast fetal MRI.
AB  - Fetal magnetic resonance imaging (MRI) is a useful adjunct to ultrasound in the
      evaluation of neural tube defects. The development of ultrafast imaging
      techniques has contributed to the increasing clinical use of fetal MRI. This
      review summarizes the utility, safety and technical aspects of fetal MRI and the
      role it plays in the evaluation of myelomeningocele. Emphasis is placed on the
      benefit of fetal MRI as it pertains to presurgical planning and perinatal
      management.

PMID- 25059406
TI  - Efficacy and safety of canagliflozin in patients with type 2 diabetes and stage 3
      nephropathy.
AB  - BACKGROUND/AIMS: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are
      approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with
      an estimated glomerular filtration rate (eGFR) of >=45 ml/min/1.73 m(2). The
      efficacy and safety of canagliflozin, an approved SGLT2 inhibitor, was evaluated
      in patients with stage 3 chronic kidney disease (CKD; eGFR >=30 to <60
      ml/min/1.73 m(2)). METHODS: This analysis used integrated data from four
      randomized, placebo-controlled, phase 3 studies that enrolled patients with T2DM
      and stage 3 CKD. RESULTS are presented for the overall population as well as
      subgroups with stage 3a CKD (eGFR >=45 and <60 ml/min/1.73 m(2)) and stage 3b CKD
      (eGFR >=30 and <45 ml/min/1.73 m(2)). RESULTS: Among all subjects studied with
      stage 3 CKD, placebo-subtracted reductions in HbA1c (-0.38 and -0.47%; p <
      0.001), body weight (-1.6 and -1.9%; p < 0.001), and systolic blood pressure (
      2.8 and -4.4 mm Hg; p < 0.01) were seen with canagliflozin 100 and 300 mg,
      respectively. Decreases in HbA1c, body weight, and systolic blood pressure were
      examined in the stage 3a and 3b CKD subgroups, with greater decreases in HbA1c, 
      0.47% (-0.61, -0.32) and body weight in subjects in stage 3a CKD, -1.8% (-2.3, 
      1.2) with canagliflozin 100 mg. Initial declines in eGFR were seen early
      following treatment initiation with canagliflozin, but trended towards baseline
      over time. The most common adverse events with canagliflozin included genital
      mycotic infections and adverse events related to reduced intravascular volume
      likely secondary to osmotic diuresis. CONCLUSION: In subjects with T2DM and stage
      3 CKD, canagliflozin reduced HbA1c, body weight, and blood pressure, and was
      generally well tolerated.

PMID- 25059407
TI  - To drill or to chisel? A long-term follow-up study of 92 exostectomy procedures
      in the UK.

PMID- 25059409
TI  - MPs call for risk assessment review of safety of UK blood supply.

PMID- 25059410
TI  - The divide between "evidenced-based" approaches and practitioners of traditional
      theories of family therapy.
AB  - Evidenced-based approaches continue to grow in the field of family therapy.
      However, practicing family therapists do not always embrace these approaches. In
      this article, we explore factors contributing to practitioners' concerns with
      evidence-based treatments and suggest a broader, more clinically palatable view
      of evidenced-based treatment. We also suggest how family therapy researchers,
      practitioners, and educators might begin to close the researcher-clinician divide
      in the best interest of all concerned. 

PMID- 25059411
TI  - The therapeutic pyramid: a common factors synthesis of techniques, alliance, and
      way of being.
AB  - Common factors in therapy such as the therapeutic alliance and client motivation
      have been found to account for more change than therapy models. But common
      factors have been critiqued as only lists of variables that provide little
      practical guidance. Some researchers have demonstrated that certain common
      elements (e.g., the therapeutic alliance) account for more variance than others
      (e.g., techniques), suggesting that some factors should be emphasized over
      others. Such findings suggest the need for alternatives to model-based therapy,
      with one alternative being meta-models, or "models of models," that focus on how
      therapeutic factors interact with each other to produce change. The purpose of
      this article is to propose a meta-model describing the relationship between two
      specific common factors-the therapeutic alliance and interventions. We also
      propose a new factor-a therapist's way of being-that we believe is foundational
      to effective therapy. The model is proposed in pyramid format, with techniques on
      top, the therapeutic alliance in the middle, and therapist way of being as the
      foundation. The hierarchical relationships between these three concepts are
      discussed, along with implications for training, research, and therapy. 

PMID- 25059412
TI  - Interpersonal forgiveness in emotion-focused couples' therapy: relating process
      to outcome.
AB  - The objective of this study was to relate the in-session processes involved in
      interpersonal forgiveness to outcome. The sample consisted of 33 couples who
      received 10-12 sessions of Emotion-focused couple therapy with the aim of
      resolving various forms of emotional injuries (i.e., transgression that violates
      the expectations of a close relationship, which leaves one partner feeling hurt
      and angry). The results of the present study were based on the analyses of 205
      video-taped segments from 33 couples' therapies. Hypotheses relating the role of
      three in-session components of resolution, the injurer's "expression of shame";
      the injured partner's "accepting response" to the shame, and the injured
      partner's "in-session expression of forgiveness", to outcome were tested using
      hierarchical linear regression analyses. Outcome measures included the Enright
      Forgiveness Inventory (The Enright Forgiveness Inventory user's manual. Madison:
      The International Forgiveness Institute, 2000), the Dyadic Adjustment Scale
      (Journal of Marriage and Family, 1976; 13: 723) and the The Interpersonal Trust
      Scale (Trust; Journal of Personality and Social Psychology, 1985; 49: 95). 

PMID- 25059408
TI  - In search of neural endophenotypes of postpartum psychopathology and disrupted
      maternal caregiving.
AB  - This is a selective review that provides the context for the study of perinatal
      affective disorder mechanisms and outlines directions for future research. We
      integrate existing literature along neural networks of interest for affective
      disorders and maternal caregiving: (i) the salience/fear network; (ii) the
      executive network; (iii) the reward/social attachment network; and (iv) the
      default mode network. Extant salience/fear network research reveals disparate
      responses and corticolimbic coupling to various stimuli based upon a
      predominantly depressive versus anxious (post-traumatic stress disorder) clinical
      phenotype. Executive network and default mode connectivity abnormalities have
      been described in postpartum depression (PPD), although studies are very limited
      in these domains. Reward/social attachment studies confirm a robust ventral
      striatal response to infant stimuli, including cry and happy infant faces, which
      is diminished in depressed, insecurely attached and substance-using mothers. The
      adverse parenting experiences received and the attachment insecurity of current
      mothers are factors that are associated with a diminution in infant stimulus
      related neural activity similar to that in PPD, and raise the need for additional
      studies that integrate mood and attachment concepts in larger study samples.
      Several studies examining functional connectivity in resting state and emotional
      activation functional magnetic resonance imaging paradigms have revealed
      attenuated corticolimbic connectivity, which remains an important outcome that
      requires dissection with increasing precision to better define neural treatment
      targets. Methodological progress is expected in the coming years in terms of
      refining clinical phenotypes of interest and experimental paradigms, as well as
      enlarging samples to facilitate the examination of multiple constructs.
      Functional imaging promises to determine neural mechanisms underlying maternal
      psychopathology and impaired caregiving, such that earlier and more precise
      detection of abnormalities will be possible. Ultimately, the discovery of such
      mechanisms will promote the refinement of treatment approaches toward maternal
      affective disturbance, parenting behaviours and the augmentation of parenting
      resiliency. 

PMID- 25059413
TI  - Effects of sex, sexual orientation, infidelity expectations, and love on distress
      related to emotional and sexual infidelity.
AB  - The purpose of this study was to investigate the influence of participant sex,
      sexual orientation, infidelity expectations, and love on emotional responses to
      emotional and sexual infidelity. Participants (72 lesbian women, 114 heterosexual
      women, 53 gay men, and 57 heterosexual men) completed a demographic form,
      continuous emotion ratings in response to hypothetical infidelity scenarios, the
      Infidelity Expectations Questionnaire (IEQ), and the Triangular Love Scale. Sex,
      sexual orientation, and commitment and intimacy among partners were significant
      predictors of various emotional responses to sexual and emotional infidelity.
      Alternatively, passion among partners and expectations about a partner's
      likelihood of committing infidelity were not significant predictors of emotional
      reactions to infidelity. Across participants, sexual infidelity elicited more
      distressing feelings than emotional infidelity. Group differences were also
      found, with women responding with stronger emotions to emotional and sexual
      infidelity than men, and heterosexuals rating emotional and sexual infidelity as
      more emotionally distressing than lesbian and gay individuals. Sex and sexual
      orientation differences emerged regarding the degree to which specific emotions
      were reported in response to sexual and emotional infidelity. Clinical
      implications are offered, including how mental health professionals might use
      these findings to help clients cope with the negative effects of infidelity on
      romantic relationships. 

PMID- 25059414
TI  - Couple's relationship with diabetes: means and meanings for management success.
AB  - Diabetes is a serious chronic illness that involves individuals, couples, and
      families in complex reciprocal interactions with the illness and other life
      dimensions. A major issue in diabetes management is how well the patient is able
      to follow the established medical regimen of selfcare. Situated within personal,
      physical, and social contexts, the meaning that a couple creates and the emotions
      they feel in their adaptation to living with diabetes and its demanding regimen
      can be viewed as the couple's relationship with diabetes. 

PMID- 25059415
TI  - Studying circular questioning "in situ": discourse analysis of a first systemic
      family therapy session.
AB  - The present article focuses on the study of circular questioning "in situ," that
      is, in the context of the discursive arena of an actual first systemic family
      therapy session. Two typical circular questions are selected, and discourse
      analysis heavily drawing from the discursive action model is deployed with the
      aim to highlight their function in the context of therapist and family members'
      problem talk. The analysis demonstrates the gradual building of two respective
      patterns, which both exhibit signs of shifts toward the instillment of a systemic
      epistemology in relation to problem talk: a shift from homogeneity to
      heterogeneity in family members' voices, which legitimizes the existence of
      different viewpoints within a system, and a shift from the construction of an
      accusation toward its deconstruction, which challenges the linear perception of
      causality underlying the accusation, thus introducing a more circular
      perspective. Implications are discussed in relation to contemporary,
      constructionist systemic family therapy practice, and reference is made to the
      methodological "promises" and challenges of the deployment of discourse analysis
      for the scrutiny of systemic family therapy therapeutic techniques and tools
      under a discursively informed light. 

PMID- 25059416
TI  - Navigating dual relationships in rural communities.
AB  - The literature examining dual relationships in rural communities is limited, and
      existing ethical guidelines lack guidelines about how to navigate these complex
      relationships. This study uses grounded theory to explore rural therapists'
      perceptions of dual relationship issues, the perceived impact of minority and/or
      religious affiliation on the likelihood of dual relationships, and the ways rural
      therapists handle inevitable dual relationship situations. All of the therapists
      who participated in the study practiced in small communities and encountered dual
      relationship situations with regularity. The overarching theme that emerged from
      the data was that of using professional judgment in engaging in the relationship,
      despite the fact that impairment of professional judgment is the main objection
      to dual relationships. This overall theme contained three areas where
      participants felt they most needed to use their judgment: the level of benefit or
      detriment to the client, the context, and the nature of the dual relationship.
      Surprisingly, supervision and/or consultation were not mentioned by the
      participants as strategies for handling dual relationships. The results of this
      study are compared with established ethical decision-making models, and
      implications for the ethical guidelines and appropriate ethical training are
      suggested. 

PMID- 25059419
TI  - Photosynthetic responses and accumulation of mesotrione in two freshwater algae.
AB  - Mesotrione is a herbicide used for killing annual grasses and broad-leaved weeds
      in maize. A recent investigation has shown that mesotrione has been detected as
      an organic contaminant in aquatic environments and may have a negative impact on
      aquatic organisms. To evaluate the eco-toxicity of mesotrione to algae,
      experiments focusing on photosynthetic responses and mesotrione accumulation in
      Microcystis sp. and Scenedesmus quadricauda were carried out. Both algae treated
      with mesotrione at 0.05-10 mg L(-1) for 7 days reduced the photosynthetic
      capacity. The fluorescence of chlorophyll a, the maximal PSII activity (Fv/Fm),
      and the parameters (Ik, alpha and ETRmax) of rapid light curves (RLCs) in both
      algae were decreased under mesotrione exposure. The 96 h EC50 values for
      mesotrione on S. quadricauda and Microcystis sp. were 4.41 and 6.19 mg L(-1),
      respectively. The latter shows more tolerance to mesotrione. Mesotrione was shown
      to be readily accumulated by both species. Such uptake of mesotrione led to the
      rapid removal of mesotrione from the medium. Overall, this study represents the
      initial comprehensive analyses of Microcystis sp. and S. quadricauda in
      adaptation to the mesotrione contaminated aquatic ecosystems. 

PMID- 25059418
TI  - Inflammatory conditions distinctively alter immunological functions of Langerhans
      like cells and dendritic cells in vitro.
AB  - The specific function of human skin-resident dendritic cell (DC) subsets in the
      regulation of immunity or tolerance is still a matter of debate. Langerhans cells
      (LC) induce anti-viral immune responses but, conversely to dermal DC, maintain
      tolerance to bacteria. However, the definite function of epidermal LC and
      cutaneous DC appears even more complex under inflammatory conditions. Here we
      investigated the immune responses of human immature monocyte-derived DC (MoDC)
      and LC-like cells (MoLC) upon stimulation with different Toll-like receptor
      ligands in the presence or absence of pro-inflammatory cytokines tumour necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). In MoDC, bacterial
      antigens selectively up-regulated CD83 and CD86 expression and induced the
      release of T helper type 1 (Th1) and Th17 cytokines and led to a higher CCR7
      dependent migratory capacity compared with a low responsiveness of MoLC.
      Importantly, MoLC activation with lipopolysaccharide under inflammatory
      conditions strongly enhanced a phenotypically mature state, increased IL-12p70,
      IL-23 and IL-6 production and Th1 cytokine secretion by CD4(+) T cells. Treatment
      with poly(I:C) specifically up-regulated surface expression of co-stimulatory
      molecules and increased release of IL-12p70 in MoLC and co-stimulation with TNF
      alpha and IL-1beta further elevated Th1 and Th17 cytokine production. Poly(I:C)
      induced up-regulation of type I interferon mRNA levels in MoLC and MoDC was Toll
      like receptor 3-dependent but not, or only weakly, modulated by pro-inflammatory
      cytokines. Our results indicate that inflammatory conditions greatly facilitate
      recognition of bacteria by MoLC. Furthermore, we suggest a critical involvement
      of both subsets in innate defence against viruses, whereas inflammatory skin
      environments additionally favour MoLC as potent inducers of Th1 and Th17
      cytokines. 

PMID- 25059420
TI  - Psychosocial status and mental health in adolescents before and after bariatric
      surgery: a systematic literature review.
AB  - OBJECTIVE: As long-term results of conservative treatment for obesity are
      discouraging, bariatric surgery is becoming a treatment option for extremely
      obese adolescents. However, mental and behavioral problems need to be respected
      when treating this vulnerable target group. METHODS: A detailed systematic
      literature review on pre- and post-operative depressive, anxiety and eating
      disorder symptoms of adolescent patients was performed in PsychINFO, PubMed and
      Medline electronic databases. RESULTS: Twelve studies met the inclusion criteria.
      Although strength of evidence was limited, results suggested that pre-operatively
      a third of adolescents suffered from moderate to severe depressive disorder
      symptoms and a quarter from anxiety disorder symptoms, while a substantial number
      showed eating disorder symptoms. Post-operatively, levels of depressive disorder
      symptoms significantly improved. Original articles on outcomes of eating and
      anxiety disorder symptoms after weight loss surgery were not found. CONCLUSIONS:
      Further attention is needed on consistent clinical assessment of mental health
      disturbances and their consecutive treatment in adolescents. Future research
      should also focus on psychological and psychosocial predictors of weight loss
      after bariatric surgery.

PMID- 25059421
TI  - Identifying patient-level health and social care costs for older adults
      discharged from acute medical units in England.
AB  - BACKGROUND: acute medical units allow for those who need admission to be
      correctly identified, and for those who could be managed in ambulatory settings
      to be discharged. However, re-admission rates for older people following
      discharge from acute medical units are high and may be associated with
      substantial health and social care costs. OBJECTIVE: identifying patient-level
      health and social care costs for older people discharged from acute medical units
      in England. DESIGN: a prospective cohort study of health and social care resource
      use. SETTING: an acute medical unit in Nottingham, England. PARTICIPANTS: four
      hundred and fifty-six people aged over 70 who were discharged from an acute
      medical unit within 72 h of admission. METHODS: hospitalisation and social care
      data were collected for 3 months post-recruitment. In Nottingham, further
      approvals were gained to obtain data from general practices, ambulance services,
      intermediate care and mental healthcare. Resource use was combined with national
      unit costs. RESULTS: costs from all sectors were available for 250 participants.
      The mean (95% CI, median, range) total cost was L1926 (1579-2383, 659, 0-23,612).
      Contribution was: secondary care (76.1%), primary care (10.9%), ambulance service
      (0.7%), intermediate care (0.2%), mental healthcare (2.1%) and social care
      (10.0%). The costliest 10% of participants accounted for 50% of the cost.
      CONCLUSIONS: this study highlights the costs accrued by older people discharged
      from acute medical units (AMUs): they are mainly (76%) in secondary care and half
      of all costs were incurred by a minority of participants (10%).

PMID- 25059423
TI  - Intimate partner violence among adolescents and young women: prevalence and
      associated factors in nine countries: a cross-sectional study.
AB  - BACKGROUND: Little is known about the prevalence of intimate partner violence
      (IPV) and its associated factors among adolescents and younger women. METHODS:
      This study analyzed data from nine countries of the WHO Multi-country Study on
      Women's Health and Domestic Violence against Women, a population based survey
      conducted in ten countries between 2000 and 2004. RESULTS: The lifetime
      prevalence of IPV ranged from 19 to 66 percent among women aged 15 to 24, with
      most sites reporting prevalence above 50 percent. Factors significantly
      associated with IPV across most sites included witnessing violence against the
      mother, partner's heavy drinking and involvement in fights, women's experience of
      unwanted first sex, frequent quarrels and partner's controlling behavior.
      Adolescent and young women face a substantially higher risk of experiencing IPV
      than older women. CONCLUSION: Adolescence and early adulthood is an important
      period in laying the foundation for healthy and stable relationships, and women's
      health and well-being overall. Ensuring that adolescents and young women enjoy
      relationships free of violence is an important investment in their future.

PMID- 25059424
TI  - Association analysis of polymorphisms in OAS1 with susceptibility and severity of
      hand, foot and mouth disease.
AB  - Hand, foot and mouth disease (HFMD) is a common childhood illness that mainly
      affects Asian children under the age of 5 years. Human enterovirus 71 (EV71) and
      coxsackievirus A16 (CA16) are the most common pathogens of HFMD. It is imperative
      that the susceptible population is screened early and that the severe illness
      population can be identified via genetic variation detection in children. Four
      single-nucleotide polymorphisms (SNP) [2'-5'-oligoadenylate synthetase1 (OAS1)
      rs10774671, selectin P ligand (SELPLG) rs2228315, scavenger receptor class B
      member 2 (SCARB2) rs41284767 and interleukin 28B (IL28B) rs12979860] were
      determined by Taqman assays in 333 HFMD samples and 163 control samples. The
      rs2228315, rs41284767 and rs12979860 polymorphisms did not differ significantly
      between HFMD patients and the controls, but the prevalence of the rs10774671
      polymorphism was significantly different between the control children and
      children infected with CA16 (GG genotype vs. AA + AG genotype, P < 0.05).
      Children with the GG genotype were more susceptible to CA16-type HFMD.
      Furthermore, the rs10774671 genotype distribution was clearly different between
      children with severe HFMD and those with mild HFMD [P < 0.05, OR 0.240, 95% CI
      (0.071-0.809)]. HFMD children with the AA+AG genotype were more likely to
      progress to encephalitis than were those with the GG genotype. Plasma gamma
      interferon (IFN) expression levels among control children and the mild and severe
      HFMD children were detected by ELISA. Those with mild HFMD had higher gamma-IFN
      expression levels compared with those with severe HFMD (P < 0.05). In addition,
      there is a significant correlation between gamma-IFN levels and OAS1 rs10774671
      SNP, as analysed by linear correlation assay. The GG genotype correlated with
      higher gamma-IFN levels (P < 0.05). In short, the OAS1 rs10774671 SNP GG genotype
      contributed to CA16 susceptibility and was associated with the development of
      mild HFMD. 

PMID- 25059422
TI  - Arterial stiffness, central pressures, and incident hospitalized heart failure in
      the chronic renal insufficiency cohort study.
AB  - BACKGROUND: Chronic kidney disease is associated with an increased risk of heart
      failure (HF). We aimed to evaluate the role of large artery stiffness, brachial,
      and central blood pressure as predictors of incident hospitalized HF in the
      Chronic Renal Insufficiency Cohort (CRIC), a multiethnic, multicenter prospective
      observational study of patients with chronic kidney disease. METHODS AND RESULTS:
      We studied 2602 participants who were free of HF at baseline. Carotid-femoral
      pulse wave velocity (CF-PWV; the gold standard index of large artery stiffness),
      brachial, and central pressures (estimated via radial tonometry and a generalized
      transfer function) were assessed at baseline. Participants were prospectively
      followed up to assess the development of new-onset hospitalized HF. During 3.5
      years of follow-up, 154 participants had a first hospital admission for HF. CF
      PWV was a significant independent predictor of incident hospitalized HF. When
      compared with the lowest tertile, the hazard ratios among subjects in the middle
      and top CF-PWV tertiles were 2.33 (95% confidence interval, 1.37-3.97; P=0.002)
      and 5.24 (95% confidence interval, 3.22-8.53; P<0.0001), respectively. After
      adjustment for multiple confounders, the hazard ratios for the middle and top CF
      PWV tertiles were 1.95 (95% confidence interval, 0.92-4.13; P=0.079) and 3.01
      (95% confidence interval, 1.45-6.26; P=0.003), respectively. Brachial systolic
      and pulse pressure were also independently associated with incident hospitalized
      HF, whereas central pressures were less consistently associated with this end
      point. The association between CF-PWV and incident HF persisted after adjustment
      for systolic blood pressure. CONCLUSIONS: Large artery stiffness is an
      independent predictor of incident HF in chronic kidney disease, an association
      with strong biological plausibility given the known effects of large artery
      stiffening of left ventricular pulsatile load.

PMID- 25059425
TI  - Neuronal glycogen synthesis contributes to physiological aging.
AB  - Glycogen is a branched polymer of glucose and the carbohydrate energy store for
      animal cells. In the brain, it is essentially found in glial cells, although it
      is also present in minute amounts in neurons. In humans, loss-of-function
      mutations in laforin and malin, proteins involved in suppressing glycogen
      synthesis, induce the presence of high numbers of insoluble polyglucosan bodies
      in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the
      aggressive neurodegeneration seen in Lafora's disease. Polysaccharide-based
      aggregates, called corpora amylacea (CA), are also present in the neurons of aged
      human brains. Despite the similarity of CA to LBs, the mechanisms and functional
      consequences of CA formation are yet unknown. Here, we show that wild-type
      laboratory mice also accumulate glycogen-based aggregates in the brain as they
      age. These structures are immunopositive for an array of metabolic and stress
      response proteins, some of which were previously shown to aggregate in
      correlation with age in the human brain and are also present in LBs. Remarkably,
      these structures and their associated protein aggregates are not present in the
      aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic
      intervention in Drosophila prevents the accumulation of glycogen clusters in the
      neuronal processes of aged flies. Most interestingly, targeted reduction of
      Drosophila glycogen synthase in neurons improves neurological function with age
      and extends lifespan. These results demonstrate that neuronal glycogen
      accumulation contributes to physiological aging and may therefore constitute a
      key factor regulating age-related neurological decline in humans. 

PMID- 25059426
TI  - Global sensitivity analysis used to interpret biological experimental results.
AB  - Modeling host/pathogen interactions provides insight into immune defects that
      allow bacteria to overwhelm the host, mechanisms that allow vaccine strategies to
      be successful, and illusive interactions between immune components that govern
      the immune response to a challenge. However, even simplified models require a
      fairly high dimensional parameter space to be explored. Here we use global
      sensitivity analysis for parameters in a simple model for biofilm infections in
      mice. The results indicate which parameters are insignificant and are 'frozen' to
      yield a reduced model. The reduced model replicates the full model with high
      accuracy, using approximately half of the parameter space. We used the
      sensitivity to investigate the results of the combined biological and
      mathematical experiments for osteomyelitis. We are able to identify parts of the
      compartmentalized immune system that were responsible for each of the
      experimental outcomes. This model is one example for a technique that can be used
      generally. 

PMID- 25059427
TI  - Political experiences of changing the focus in elderly care in one municipality.
AB  - AIM: To describe local politicians' experiences of an ongoing planning process
      for elderly care for the future in a medium-sized municipality in western Sweden.
      BACKGROUND: Elderly care is facing challenges because of an ageing population.
      METHOD: The study comprised a total of eight semi-structured interviews with
      politicians. The interviews were analysed using manifest qualitative content
      analysis. RESULTS: One category (political consensus) and three subcategories
      (involvement generates security, trust in change management and confidence to
      create visions) were identified. CONCLUSIONS: Political consensus across elderly
      care organisations could establish a sense of security for old people, their
      relatives and the staff in particular. Continuous information and support from
      different managerial levels is one way of implementing changes within large
      organisations. However, further research is needed to describe how to develop
      future elderly care. IMPLICATIONS FOR NURSING MANAGEMENT: An ageing population
      requires cooperation across provider boundaries to further develop high-quality
      elderly care services. Nursing leadership during a change process is crucial to
      implement political decisions in care organisations. Furthermore, active
      marketing of the health care profession for elderly care is needed as well as new
      knowledge regarding old people.

PMID- 25059428
TI  - Clinical course of gastrointestinal stromal tumor diagnosed by endoscopic
      ultrasound-guided fine-needle aspiration.
AB  - BACKGROUND AND AIM: Gastrointestinal stromal tumors (GIST) are the most common
      mesenchymal tumor of the gastrointestinal tract. However, little is known about
      the clinical presentation of GIST, especially small lesions. The purpose of the
      present study was to clarify the efficacy of endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA) for the diagnosis of GIST and to determine its
      clinical course. METHODS: Pathological and clinical records of GIST extracted
      from our institutional database between 1996 and 2012 were reviewed. All GIST
      cases were diagnosed pathologically by surgical specimen or EUS-FNA. To examine
      the efficacy of EUS-FNA for the diagnosis of GIST, the pathological findings of
      EUS-FNA were compared with the surgical findings from resected cases. Next, to
      clarify the clinical presentation of GIST, imaging findings and changes in tumor
      size over time were evaluated in follow up. RESULTS: Of 84 cases of GIST, 67 were
      resected surgically after EUS-FNA; tumor size was <20 mm in 19 patients, and >=20
      mm in 48 patients. For the diagnosis of small GIST<20 mm, sensitivity and
      positive predictive value of EUS-FNA were 81.3% and 100%, respectively. A total
      of 27 patients with GIST was follow up for more than 1 year. Tumor size increased
      significantly during follow up. However, generalized linear analysis showed that
      there was no significant relationship between tumor size and follow up period.
      CONCLUSIONS: The present results showed that even small GIST can be correctly
      identified by EUS-FNA. Moreover, size of small GIST increased significantly
      during follow up.

PMID- 25059429
TI  - The function of loud calls (Hoot Series) in wild western gorillas (Gorilla
      gorilla).
AB  - The use of loud vocal signals to reduce distance among separated social partners
      is well documented in many species; however, the underlying mechanisms by which
      the reduction of spacing occurs and how they differ across species remain
      unclear. Western gorillas (Gorilla gorilla) offer an opportunity to investigate
      these issues because their vocal repertoire includes a loud, long-distance call
      (i.e., hoot series) that is potentially used in within-group communication,
      whereas mountain gorillas use an identical call exclusively during intergroup
      encounters. First, we tested whether the hoot series functions as a
      contact/separation call. Second, we examined which individuals were more likely
      to reply and which party was more responsible for decreasing distance to identify
      the underlying mechanisms and cognitive implications of hoot series. We collected
      behavioral, spatial, and acoustic data on five adult gorillas over 15 months at
      the Mondika Research Center (Republic of Congo and CAR). Hoot series are
      individually distinct calls and given by both male and female gorillas when
      separated from each other. Following hooting, the distance between separated
      group members decreased significantly; thus we concluded that western gorillas
      use this call to reestablish group cohesion. The way in which proximity was
      achieved depended upon listeners replying or not to the caller. Replies may
      indicate a conflict between callers about intended travel direction, with vocal
      interchanges serving to negotiate a consensus. Although the acoustic features of
      vocal signals are highly constrained in closely related species, our results
      demonstrate that the function and usage of particular calls can be flexible.

PMID- 25059430
TI  - Foreword.

PMID- 25059431
TI  - Increasing role of interventional cardiologists for peripheral vascular disease.
AB  - Improvements in the design of endovascular devices and technical skills of
      interventionalists have opened new possibilities for patients with a wide range
      of peripheral vascular diseases. In lower extremity peripheral artery disease,
      percutaneous treatments have become the predominant revascularization strategy
      for simple and complex lesions. Newer generations of stents and drug-coated
      balloons have demonstrated strong potential in the treatment of femoropopliteal
      and infrainguinal diseases. One of the most dramatic advances in the recent past
      has been endovascular repair of thoracic and abdominal aortic aneurysms, which
      has become the preferred approach in lieu of open surgical repair. Contemporary
      trials have established the safety and effectiveness of carotid stenting in
      selected patients with severe stenosis. Endovascular treatments for venous
      occlusive disease have long been underutilized, but their effectiveness is being
      increasingly recognized. This review covers new endovascular procedures performed
      by interventional cardiologists for peripheral vascular diseases. 

PMID- 25059432
TI  - Data distributions in magnetic resonance images: a review.
AB  - Many image processing methods applied to magnetic resonance (MR) images directly
      or indirectly rely on prior knowledge of the statistical data distribution that
      characterizes the MR data. Also, data distributions are key in many parameter
      estimation problems and strongly relate to the accuracy and precision with which
      parameters can be estimated. This review paper provides an overview of the
      various distributions that occur when dealing with MR data, considering both
      single-coil and multiple-coil acquisition systems. The paper also summarizes how
      knowledge of the MR data distributions can be used to construct optimal parameter
      estimators and answers the question as to what precision may be achieved
      ultimately from a particular MR image. 

PMID- 25059433
TI  - Toward in situ tissue engineering: chemokine-guided stem cell recruitment.
AB  - Chemokines are potent stem cell homing and mobilization factors, and artificially
      increasing the concentrations of specific chemokines at injury sites is an up-to
      date strategy to potentiate and prolong the recruitment of endogenous stem cells
      and to amplify in situ tissue regeneration. We briefly outline the latest
      progress in stem cell recruitment focusing on the interactions of mesenchymal
      stem cells (MSCs) with chemokines, complement cascade peptides, bioactive lipids,
      and glycosaminoglycans (GAGs). We present recent advances in state-of-the-art
      chemokine delivery devices suitable for various applications and critically
      evaluate the perspectives and challenges of the chemokine-guided in situ strategy
      for translation in regenerative medicine. 

PMID- 25059434
TI  - Sonodynamic inactivation of methicillin-resistant Staphylococcus aureus in
      planktonic condition by curcumin under ultrasound sonication.
AB  - Methicillin-Resistant Staphylococcus aureus (MRSA) is an important cause of
      difficult-to-treat infections. The present study aims to investigate sonodynamic
      inactivation of MRSA in planktonic condition using curcumin under ultrasound
      sonication. Dark toxicity of curcumin to MRSA was investigated to choose the
      concentration range of curcumin used in the study. The uptake of curcumin in MRSA
      was observed before ultrasound sonication. After sonication colony forming units
      (CFUs) and bacterial viability were investigated using fluorescence assay.
      Additionally, chromosomal DNA fragmentation was also analyzed. Curcumin showed no
      dark toxicity to MRSA in the concentration range of?500MUM. The maximum uptake of
      curcumin in MRSA occurred in 50min after curcumin incubation. Counting of CFUs
      showed that curcumin had significantly sonodynamic killing effect on MRSA in a
      curcumin dose-dependent manner, and 5-log reduction in CFU was observed after
      curcumin treatment (40MUM) at room temperature in the dark for 50min followed by
      exposure to ultrasound with intensity of 1.56W/cm(2) for 5min. The ratio of green
      fluorescent intensity to red-fluorescent intensity was obviously decreased after
      curcumin treatment under ultrasound sonication. No significant change in
      chromosomal DNA was found in the cultured MRSA after the combined treatment of
      curcumin and ultrasound. These results demonstrated that sonodynamic action of
      curcumin had significant inactivation of MRSA in planktonic condition. 

PMID- 25059435
TI  - The behavior of lipid debris left on cell surfaces from microbubble based
      ultrasound molecular imaging.
AB  - Lipid monolayer coated microbubbles are currently being developed to identify
      vascular regions that express certain surface proteins as part of the new
      technique of ultrasound molecular imaging. The microbubbles are functionalized
      with targeting ligands which bind to the desired cells holding the microbubbles
      in place as the remaining unbound microbubbles are eliminated from circulation.
      Subsequent scanning with ultrasound can detect the highly reflectant microbubbles
      that are left behind. The ultrasound scanning and detection process results in
      the destruction of the microbubble, creating lipid fragments from the monolayer.
      Here we demonstrate that microbubbles targeted to 4T1 murine breast cancer cells
      and human umbilical cord endothelial cells leave behind adhered fragments of the
      lipid monolayer after exposure to ultrasound with peak negative pressures of 0.18
      and 0.8MPa. Most of the observed fragments were large enough to be resistant to
      receptor mediated endocytosis. The fragments were not observed to incorporate
      into the lipid membrane of the cell over a period of 96min. They were not
      observed to break into smaller pieces or significantly change shape but they were
      observed to undergo translation and rotation across the cell surface as the cells
      migrated over the substrate. These large fragments will apparently remain on the
      surface of the targeted cells for significant periods of time and need to be
      considered for their potential effects on blood flow through the microcapillaries
      and potential for immune system recognition. 

PMID- 25059436
TI  - 14-3-3 epsilon prevents G2/M transition of fertilized mouse eggs by binding with
      CDC25B.
AB  - BACKGROUND: The 14-3-3 (YWHA) proteins are highly conserved in higher eukaryotes,
      participate in various cellular signaling pathways including cell cycle
      regulation, development and growth. Our previous studies demonstrated that 14-3
      3epsilon (YWHAE) is responsible for maintaining prophase | arrest in mouse
      oocyte. However, roles of 14-3-3epsilon in the mitosis of fertilized mouse eggs
      have remained unclear. Here, we showed that 14-3-3epsilon interacts and
      cooperates with CDC25B phosphorylated at Ser321 regulating G2/M transition of
      mitotic progress of fertilized mouse eggs. RESULTS: Disruption of 14-3-3epsilon
      expression by RNAi prevented normal G2/M transition by inhibition of MPF activity
      and leaded to the translocation of CDC25B into the nucleus from the cytoplasm.
      Overexpression of 14-3-3epsilon-WT and unphosphorylatable CDC25B mutant (CDC25B
      S321A) induced mitotic resumption in dbcAMP-arrested eggs. In addition, we
      examined endogenous and exogenous distribution of 14-3-3epsilon and CDC25B.
      Endogenous 14-3-3epsilon and CDC25B were co-localized primarily in the cytoplasm
      at the G1, S, early G2 and M phases whereas CDC25B was found to accumulate in the
      nucleus at the late G2 phase. Upon coexpression with RFP-14-3-3epsilon, GFP
      CDC25B-WT and GFP-CDC25B-S321A were predominantly cytoplasmic at early G2 phase
      and then GFP-CDC25B-S321A moved to the nucleus whereas CDC25B-WT signals were
      observed in the cytoplasm without nucleus accumulation at late G2 phase at
      presence of dbcAMP. CONCLUSIONS: Our data indicate that 14-3-3epsilon is required
      for the mitotic entry in the fertilized mouse eggs. 14-3-3epsilon is primarily
      responsible for sequestering the CDC25B in cytoplasm and 14-3-3epsilon binding to
      CDC25B-S321 phosphorylated by PKA induces mitotic arrest at one-cell stage by
      inactivation of MPF in fertilized mouse eggs.

PMID- 25059437
TI  - What is frontotemporal dementia?
AB  - Frontotemporal dementia (FTD) is the clinical manifestation of progressive nerve
      cell loss in the frontal and anterior temporal lobes. It represents the second
      most frequent form of early-onset dementia. The two major types of FTD are
      determined by the localisation of the underlying pathology. The behaviour variant
      is characterised by disinhibition, socially inappropriate manners, loss of
      empathy, blunting of affect and hyperorality. Key features of the language
      variant are either non-fluent effortful speech and grammatical errors or impaired
      word finding and loss of meaning of words and objects. Histopathological changes
      are characterised by the abnormal processing of proteins including microtubule
      associated protein Tau, transactive response DNA-binding protein, and tumour
      associated protein fused in sarcoma. The familial forms of FTD are caused by
      mutations in 5 genes. The diagnosis of FTD rests on careful history and
      psychiatric, neuropsychological and neurological examination supported by
      laboratory assessments and brain imaging. The management requires an
      interdisciplinary approach involving the carer and using non-pharmacological
      approaches in the first line. Current antidementia drugs, including
      cholinesterase inhibitors and memantine, have no consistent positive effects in
      FTD. Behavioural symptoms may respond favourably to selective serotonergic
      antidepressants. Antipsychotic agents should be used with caution regarding
      motor, cardiovascular and mortality risks. 

PMID- 25059438
TI  - The influence of vascular risk factors on cognitive decline in patients with
      Alzheimer's disease.
AB  - INTRODUCTION: The influence of vascular risk factors (VRFs) on the rate of
      cognitive decline in patients with established dementia is unclear. This study
      aims to examine the association between VRFs and the rate of cognitive decline in
      patients with Alzheimer's disease (AD). METHODS: Data were obtained from patients
      visiting a memory clinic between 2004 and 2012. VRFs were determined at baseline
      and included hypertension, hypercholesterolemia, diabetes mellitus, overweight
      and smoking. Continuous values of blood pressure, total cholesterol, glucose
      level and body mass index were also obtained. Mini-Mental State Exam (MMSE)
      scores were obtained at baseline and during follow-up visits. The association
      between VRFs and the annual change in MMSE scores was analysed with a
      multivariable linear mixed model adjusted for age, sex and the aforementioned
      VRFs. RESULTS: From 174 patients (mean age 78.3 years), with a follow-up time up
      to 5.8 years (mean 1.1 year), in total 447 MMSE scores were obtained. The
      multivariable analyses showed an association between age as well as systolic
      blood pressure and a decline in annual rates of change in MMSE scores of -0.05
      (95% confidence interval (CI): -0.09 to 0.00) and -0.01 (CI: -0.03 to 0.00),
      respectively. For all other VRFs, including sex, patients did not show a
      significant difference. CONCLUSION: This study did not find an association
      between preventable vascular risk factors and cognitive decline in patients with
      AD, except for systolic blood pressure. As the association between systolic blood
      pressure and decline in MMSE was small, clinical relevance may be limited.

PMID- 25059439
TI  - Patients' views on the effectiveness of patient-held records: a systematic review
      and thematic synthesis of qualitative studies.
AB  - OBJECTIVE: To synthesise the views of patients on patient-held records (PHR) and
      to determine from a patient's perspective the effectiveness and any benefits or
      drawbacks to the PHR. DESIGN: Systematic review and thematic synthesis of
      qualitative studies, which investigate the perspective of patients on the
      effectiveness of the PHR. DATA SOURCES: Medline, CINAHL, PsychINFO, PubMed,
      Cochrane. REVIEW METHODS: Systematic review of literature relevant to the
      research question and thematic synthesis involving line by line coding of the
      quotations from participants and the interpretations of the findings offered by
      authors. RESULTS: Ten papers that reported the experiences of 455 patients were
      included in the thematic synthesis. Five studies focused on cancer care, two on
      mental health, one on antenatal care, one on chronic disease and one on learning
      disability. The completeness of reporting was variable. Three main themes were
      identified: (i) practical benefits of the PHR (having a record of one's
      condition, an aide memoire, useful information source and tool for sharing
      information across the health system); (ii) psychological benefits of the PHR
      (empowered to ask questions, a place to record thoughts and feelings and feeling
      in control); and (iii) drawbacks to the PHR (PHR imposes unwanted responsibility
      and ineffectiveness). CONCLUSIONS: The effectiveness of the PHR is largely
      dependent upon uptake across the health system from patients and health-care
      providers alike. Robust qualitative studies are needed, which offer more complete
      reporting and examine what patients want and need from a PHR.

PMID- 25059440
TI  - Functional assessment of mycosporine-like amino acids in Microcystis aeruginosa
      strain PCC 7806.
AB  - The biological role of the widespread mycosporine-like amino acids (MAAs) in
      cyanobacteria is under debate. Here, we have constructed and characterized two
      mutants impaired in MAA biosynthesis in the bloom-forming cyanobacterium
      Microcystis aeruginosa PCC 7806. We could identify shinorine as the sole MAA type
      of the strain, which is exclusively located in the extracellular matrix.
      Bioinformatic studies as wells as polymerase chain reaction screening revealed
      that the ability to produce MAAs is sporadically distributed within the genus.
      Growth experiments and reactive oxygen species quantification with wild-type and
      mutant strains did not support a role of shinorine in protection against UV or
      other stress conditions in M. aeruginosa PCC 7806. The shinorine content per dry
      weight of cells as well as transcription of the mys gene cluster was not
      significantly elevated in response to UV-A, UV-B or any other stress condition
      tested. Remarkably, both mutants exhibited pronounced morphological changes
      compared with the wild type. We observed an increased accumulation and an
      enhanced hydrophobicity of the extracellular matrix. Our study suggests that MAAs
      in Microcystis play a negligible role in protection against UV radiation but
      might be a strain-specific trait involved in extracellular matrix formation and
      cell-cell interaction.

PMID- 25059441
TI  - Novel type of VanB2 teicoplanin-resistant hospital-associated Enterococcus
      faecium.
AB  - Seven high-risk clones of vancomycin-resistant Enterococcus faecium (VREF)
      belonging to clonal complex 17 were identified using multilocus sequence typing
      (MLST) among clinical isolates from Saudi Arabia. Among these isolates, a new
      hospital-associated sequence type (ST795), VanB(2)-type teicoplanin-resistant
      strain was detected. Its unusual phenotype resulted from a new combination of
      mutations in the ddl, vanS and vanW genes, which confirmed the trend of evolution
      in VanB-type resistance. Furthermore, characteristics of adaptation and
      persistence in the hospital environment of ST795 were emphasised by the presence
      of genes and clusters recognised to be specific for hospital-associated VREF.

PMID- 25059442
TI  - Salmonella enterica serovar Typhimurium multidrug efflux pumps EmrAB and AcrEF
      support the major efflux system AcrAB in decreased susceptibility to triclosan.

PMID- 25059443
TI  - Response to: tigecycline and pneumonia.

PMID- 25059444
TI  - Carbapenem and multidrug resistance in Gram-negative bacteria in a single centre
      in Italy: considerations on in vitro assay of active drugs.
AB  - In intensive care units (ICUs), the most important causes of nosocomial bacterial
      infections are mainly multidrug-resistant (MDR) and extensively drug-resistant
      (XDR) Acinetobacter baumannii and Klebsiella pneumoniae strains. Mortality
      related to these infections is very high due to lack of effective therapy and the
      severity of patient conditions. This study aimed to assess the prevalence of
      carbapenem resistance genes in 77 carbapenem-resistant Gram-negative bacteria
      isolated from severe infections (bloodstream, pulmonary and urinary tract) during
      the period 1 January to 31 July 2013 in a general ICU in Catania, Italy, and to
      examine their susceptibility to tigecycline and colistin using two different
      methods. In total, 52 A. baumannii belonging to the same sequence type (ST) 2
      clone and carrying the bla(OXA-23) gene as well as 25 K. pneumoniae carrying
      bla(KPC-3) were isolated. Four distinct pulsotypes were identified in K.
      pneumoniae, which correlated with four distinct STs: ST258 and ST512, spread
      worldwide, and ST147 and ST395 detected for the first time in Italy. A. baumannii
      isolates showed an XDR profile and were fully susceptible only to colistin; all
      KPC-producing K. pneumoniae isolates were MDR, whilst colistin was active against
      19 of 25 strains. These results show that broth microdilution (BMD) is a reliable
      in vitro susceptibility test for colistin, above all K. pneumoniae, whilst both
      the gradient test and BMD are suitable for tigecycline susceptibility testing of
      A. baumannii.

PMID- 25059445
TI  - Tigecycline and pneumonia.

PMID- 25059446
TI  - Impact of structured personal on-site patient education on low posaconazole
      plasma concentrations in patients with haematological malignancies.
AB  - Low posaconazole plasma concentrations (PPCs) are associated with breakthrough
      invasive mould infections among patients with haematological malignancies. This
      study evaluated the influence of structured personal on-site patient education on
      low PPCs. The study was conducted from July 2012 to May 2013 at the Division of
      Hematology, Medical University Hospital of Graz (Graz, Austria). PPCs were
      measured in all patients with haematological malignancies receiving the drug
      prophylactically. Concentrations above the target of 0.5 mg/L were defined as
      satisfactory and those below this concentration as low. In patients with low
      PPCs, structured personal on-site education regarding the intake of posaconazole
      (e.g. intake with fatty/acid food, prevention of nausea and vomiting) was
      performed. In total, 258 steady-state PPCs were measured in 65 patients [median
      PPC 0.59 mg/L, interquartile range 0.25-0.92 mg/L; 141/258 (54.7%) satisfactory].
      Diarrhoea was the strongest predictor of low PPCs in the multivariate analysis.
      Initial steady-state PPCs were sufficient in 29 patients and low in 36 patients.
      Of the 36 patients with low initial steady-state PPCs, 8 were either discharged
      or antifungal therapy was modified before a follow-up PPC was obtained; in the
      remaining 28 patients, personal on-site education was performed. In 12/28
      patients (43%) the personal on-site education led to sufficient levels, whilst in
      16 (57%) PPCs stayed below the target, although increasing from <0.2 mg/L to >0.3
      mg/L in 6 of these patients. In conclusion, personal education appears to be a
      promising tool to increase low PPCs.

PMID- 25059447
TI  - Emergence of carbapenemase-producing Gram-negative bacteria in Saint Petersburg,
      Russia.
AB  - The emergence and spread of carbapenemase-producing Gram-negative bacteria
      represents a serious public health concern. Here we show that of 477 Gram
      negative isolates collected from 18 hospitals between November 2011 and February
      2013 in Saint Petersburg (Russia), minimum inhibitory concentrations (MICs) were
      greater than the European Committee on Antimicrobial Susceptibility Testing
      (EUCAST) epidemiological cut-off value of at least one carbapenem antibiotic in
      101 isolates (21.2%). The bla(NDM-1) gene was detected by PCR in 17 Klebsiella
      pneumoniae and 1 Acinetobacter nosocomialis isolate. Multilocus sequence typing
      (MLST) revealed that all NDM-1-producing K. pneumoniae isolates belonged to
      sequence type 340 (ST340) and harboured genes encoding additional beta
      lactamases; presence of the bla(CTX-M-1-like) gene correlated with aztreonam
      resistance, whilst its absence correlated with susceptibility. The
      epidemiological situation in Saint Petersburg can be assessed as regional spread
      of NDM-1-producers. The bla(KPC-2) gene was detected in two K. pneumoniae
      isolates (ST258 and ST273) and one Enterobacter cloacae isolate. Two E. cloacae
      isolates harboured the bla(VIM-4) gene, and one K. pneumoniae (ST395) isolate
      harboured the bla(OXA-48) gene. In NDM-1-producers, MICs of biapenem were the
      lowest compared with those of other carbapenems. Most isolates were susceptible
      to tigecycline and polymyxin, except for one K. pneumoniae isolate that was found
      to be polymyxin-resistant and one E. cloacae isolate that was tigecycline
      resistant. Only one patient with a urinary tract infection caused by KPC-2
      producing K. pneumoniae had a history of travel abroad (Southeast Asia). Thus,
      there is an actual threat of the emergence of an alarming endemic situation with
      NDM-1-producers in Saint Petersburg.

PMID- 25059448
TI  - The boy who lost his smile: facioscapulohumeral dystrophy in the head and neck.
AB  - BACKGROUND: Facioscapulohumeral dystrophy is the third most common muscular
      dystrophy and the one most likely to present primarily in the head and neck.
      METHODS: In this report, we present a case of a young child with subtle
      progressive bilateral facial weakness whose workup ultimately led to this
      diagnosis. Paralysis in this disorder is secondary to worsening muscle atrophy,
      which typically progresses in a cephalad to caudad direction. Despite facial
      paralysis being a key and early component of this illness, no prior descriptions
      in the otolaryngology literature exist. DISCUSSION: The case described is unusual
      in that the patient initially presented to a community otolaryngologist. In
      addition to workup, the disease characteristics, head and neck manifestations,
      and prognosis are discussed.

PMID- 25059449
TI  - Angiotensin converting enzyme inhibitor-related angioedema: onset, presentation,
      and management.
AB  - OBJECTIVE: This study aimed to determine the duration of use, presentation, and
      management of angiotensin converting enzyme (ACE) inhibitor-related angioedema
      patients at an urban academic medical center. METHODS: Retrospective chart
      review. RESULTS: Eighty-eight patients who presented with ACE inhibitor-related
      angioedema between January 1, 2012, and December 31, 2012, were identified. They
      presented anywhere from 1 day to 20 years after starting an ACE inhibitor. About
      half the patients (50.7%) presented after taking an ACE inhibitor for at least 1
      year. Fifty-five patients were female (62.5%). Twenty-eight patients (31.8%) had
      an airway intervention with 27 intubated and 1 requiring cricothyroidotomy. Six
      patients were intubated after more than 1 flexible laryngoscopy. The percentage
      of patients with involvement of the face, lips, tongue, floor of mouth, soft
      palate/uvula, and larynx were 12.5%, 60.2%, 39.7%, 6.8%, 17.0%, and 29.5%,
      respectively. Sixty-eight percent of patients with laryngeal edema were
      intubated. The majority of patients were treated with a corticosteroid and H1 and
      H2 receptor antagonists. CONCLUSION: Angioedema can occur at any time after
      starting ACE inhibitor use, with nearly half occurring after 1 year of use.
      Laryngeal involvement occurred in a minority of patients, but most of these
      patients were felt to require airway protection.

PMID- 25059450
TI  - Aneurysmal bone cysts of the spine: treatment options and considerations.
AB  - Aneurysmal bone cysts (ABCs) are benign bone lesions with annual incidences
      ranging from 1.4 to 3.2 cases per million people. Approximately, 10-30% of ABCs
      are found in the spine. Such lesions are traditionally treated with curettage or
      other intralesional techniques. Because ABCs can be locally aggressive,
      intralesional resection can be incomplete and result in recurrence. This has led
      to increased use of novel techniques, including selective arterial embolization
      (SAE). This study aims to: (1) compare outcomes based on extent of surgical
      resection, and (2) compare the efficacy of SAE versus surgical resection.
      Clinical data pertaining to 71 cases of spinal ABCs were ambispectively collected
      from nine institutions in Europe, North America, and Australia. Twenty-two spinal
      ABCs were treated with surgery, 32 received preoperative embolization and
      surgery, and 17 were treated with SAE. Most tumors were classified as Enneking
      stage 2 (n = 29, 41%) and stage 3 (n = 29, 41%). Local recurrence and survival
      were investigated and a significant difference was not observed between treatment
      groups. However, all three local recurrences occurred following surgical
      resection. Surgical resection was further categorized based on Enneking
      appropriateness. Recurrences only occurred following intralesional Enneking
      inappropriate (EI) resections (P = 0.10), a classification that characterized 47%
      of all surgical resections. Furthermore, 56% of intralesional resections were EI,
      compared to only 10% of en bloc resections (P = 0.01). Although SAE treatment did
      not result in any local recurrences, 35% involved more than five embolization
      procedures. Spinal ABCs can be effectively treated with intralesional resection,
      en bloc resection, or SAE. Preoperative embolization should be considered before
      intralesional resection to limit intraoperative bleeding. Treatment plans must be
      guided by lesion characteristics and clinical presentation.

PMID- 25059451
TI  - Local control after fractionated stereotactic radiation therapy for brain
      metastases.
AB  - Stereotactic radiosurgery (SRS) is frequently used in the management of brain
      metastases, but concerns over potential toxicity limit applications for larger
      lesions or those in eloquent areas. Fractionated stereotactic radiation therapy
      (SRT) is often substituted for SRS in these cases. We retrospectively analyzed
      the efficacy and toxicity outcomes of patients who received SRT at our
      institution. Seventy patients with brain metastases treated with SRT from 2006
      2012 were analyzed. The rates of local and distant intracranial progression,
      overall survival, acute toxicity, and radionecrosis were determined. The SRT
      regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor
      histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and
      melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4-6.4 cm).
      Median survival after SRT was 10.7 months. Median time to local progression was
      17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year.
      Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most
      common symptom being mild headache. Symptomatic radiation-induced treatment
      change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a
      safe and reasonably effective technique to treat brain metastases deemed less
      suitable for SRS, though dose intensification strategies may further improve
      local control.

PMID- 25059452
TI  - Retrospective review of relapse after systemic cyclosporine in children with
      atopic dermatitis.
AB  - Cyclosporine is a systemic therapy used for control of severe atopic dermatitis
      (AD) in children. Although traditionally recommended at a dose of 5 mg/kg/day for
      6 months, a longer duration of treatment may be necessary to bring a child with
      active and severe disease into remission. There are few data on the short- and
      long-term effectiveness of longer courses of therapy. This was a retrospective
      chart review of children treated with cyclosporine at a Canadian hospital
      affiliated clinic between 2000 and 2013. Fifteen patients with adequate follow-up
      were identified. Twelve (80%) were male and the mean age at initiation of
      cyclosporine was 11.2 +/- 3.4 years. The mean duration of cyclosporine therapy
      was 10.9 +/- 2.7 months (range 7-15 months) at a starting dose of 2.8 +/- 0.6
      mg/kg/day. Of 12 patients (80%) who responded to cyclosporine, 5 patients (42%)
      had relapsed at a follow-up of 22.7 +/- 15.0 months. The duration of therapy was
      longer in patients who did not relapse (17.7 +/- 10.7 months) than in those who
      did (10.2 +/- 2.7 months) (p = 0.06). Adverse events led to discontinuation in
      three patients (20%) and included infection-related complications in two patients
      and reversible renal toxicity in one. These results suggest that a longer
      duration of low-dose cyclosporine may help decrease the risk of relapse in
      patients with severe AD who are resistant to topical therapies.

PMID- 25059453
TI  - Treatment of inflammatory bowel disease patients with anti-TNF-alpha factors and
      immunosuppressives does not influence the prevalence of Helicobacter pylori
      infection.

PMID- 25059454
TI  - The prevention of fragility fractures in diabetic patients.
AB  - Patients with diabetes mellitus (DM) are at greater risk of fractures mostly due
      to not only extraskeletal factors, such as propensity to falls, but also to bone
      quality alteration, which reduces bone strength. In people with DM, insulin
      deficit and hyperglycemia seem to play a role in determining bone formation
      alteration by AGE accumulation which directly influences osteoblast activity.
      Although there are conflicting data in the literature, adequate glycemic control
      with hypoglycemic treatment may be an important element in preventing bone tissue
      alterations in both type 1 and type 2 DM. Diabetes status is a predictive of
      future hip and major osteoporosis fractures independently of BMD and FRAX
      probability. Attention should be paid to the use of thiazolidinediones,
      especially in older women, because the direct negative effect on bone could
      exceed the positive effect of glycemic control. Systematic screening for
      complications and fall prevention efforts, along with calcium and vitamin D
      repletion and adequate physical activity, represents the mainstay of fracture
      prevention in DM patients. All anticatabolic drugs (raloxifene, bisphosphonates,
      denosumab) seem to be effective in DM patients. On the basis of
      pathophysiological evidence that suggests low bone formation in DM patients,
      osteoanabolic therapies such as teriparatide might represent an important
      therapeutic option for DM patients with severe osteoporosis and/or multiple
      fractures. The search for better methods for the identification of fragility
      fracture risk in the growing population of adult and elderly subjects with DM
      might be considered a clinical priority which could improve the prevention of
      fracture in DM patients.

PMID- 25059455
TI  - Elucidating the neurophysiological underpinnings of autism spectrum disorder: new
      developments.
AB  - The study of neurophysiological approaches together with rare and common risk
      factors for Autism Spectrum Disorder (ASD) allows elucidating the specific
      underlying neurobiology of ASD. Whereas most neurophysiologically based research
      in ASD to date has focussed on case-control differences based on the DSM- or ICD
      based categorical ASD diagnosis, more recent studies have aimed at studying
      genetically and/or neurophysiologically defined homogeneous ASD subgroups for
      specific neuronal biomarkers. This review addresses the neurophysiological
      investigation of ASD by evoked and event-related potentials, by EEG/MEG
      connectivity measures such as coherence, and transcranial magnetic stimulation.
      As an example of classical neurophysiological studies in ASD, we report event
      related potential studies which have illustrated which brain areas and processing
      stages are affected in the visual perception of socially relevant stimuli.
      However, a paradigm shift has taken place in recent years focussing on how these
      findings can be tracked down to basic neuronal functions such as deficits in
      cortico-cortical connectivity and the interaction between brain areas.
      Disconnectivity, for example, can again be related to genetically induced shifts
      in the excitation/inhibition balance. Genetic causes of ASD may be grouped by
      their effects on the brain's system level to identify ASD subgroups which respond
      differentially to therapeutic interventions.

PMID- 25059456
TI  - Blepharospasm: long-term treatment with either Botox(r), Xeomin(r) or Dysport(r).
AB  - Botulinum toxin (BT) therapy is the treatment of choice for blepharospasm (BPS).
      Currently available BT type A drugs include Botox((r)), Dysport((r)) and
      Xeomin((r)). Until now, there are few long-term studies on BT therapy for BPS.
      This is the first long-term study comparing all three major BT drugs. We
      collected treatment, efficacy and adverse effect data on BPS patients treated
      with either Botox((r)), Dysport((r)) or Xeomin((r)) for at least eight
      consecutive treatments. Two hundred and eighty-eight patients (208 females, 80
      males, age 62 +/- 12 years) were included in this study. The treatment time was
      11.2 +/- 4.1 years covering 10,701 injection series. Doses were 47 +/- 10 MU for
      Botox((r)), 120 +/- 35 MU for Dysport((r)) and 62 +/- 11 MU for Xeomin((r))
      (Botox((r)) dose vs Xeomin((r)) dose: p < 0.001, unpaired t test). 85 % of all
      patients had stable doses. The onset of the therapeutic effect was after 6.1 +/-
      3.3 days and its duration lasted 10.2 +/- 3.5 weeks. The Global Clinical
      Improvement (GCI, 0 = no, 1 = slight, 2 = moderate, 3 = marked improvement in
      severity and function) as estimated by the patient was 2.5 +/- 0.6. It was stable
      in 90% of the patients. Adverse effect frequency was 3.0% (ptosis 2.3%, dry eye
      0.5%, diplopia 0.2%). None of these findings was significantly different between
      Botox((r)), Dysport((r)) and Xeomin((r)). Our study, one of the largest studies
      on BT therapy of BPS and the study with the longest follow-up, confirms that BT
      therapy produces robust clinical improvement which is stable throughout the
      treatment time. Therapeutic effects start after 6.1 days and last for about 10
      weeks before they start to vanish. With this, they are approximately 2 weeks
      shorter than the recommended inter-injection interval. Adverse effects were rare,
      mild and always transient. BT therapy is a safe and effective treatment for BSP.
      Shorter inter-injection intervals may improve therapeutic results.

PMID- 25059457
TI  - Correlations between plasma levels of amino acids and nonmotor symptoms in
      Parkinson's disease.
AB  - Converging evidence suggests that changes in plasma levels of amino acids are
      involved in Parkinson's disease (PD), but their roles in nonmotor symptoms (NMS)
      of PD remain unclear. The aim of this study was to evaluate the correlations
      between plasma amino acids and NMS of PD. Plasma levels of aspartate (Asp),
      glutamate (Glu), glycine (Gly) and gamma-aminobutyric acid (GABA) were measured
      in 92 PD patients and 60 healthy controls. Four NMS, including depression, pain,
      sleep disturbances and autonomic dysfunction were assessed in enrolled subjects
      using the Hamilton Depression Scale, the short form of the McGill Pain
      Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in
      Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple
      regression analysis was used to evaluate the correlations between plasma levels
      of amino acids and NMS. PD patients exhibited significantly higher scores of NMS
      scales and lower plasma levels of amino acids compared to healthy controls.
      Within the PD group, plasma levels of Asp and Glu were negatively associated with
      the severity of depression and sleep disturbances. Moreover, decreased plasma
      level of GABA was correlated with more severe symptoms of sleep disturbances.
      After controlling for gender, disease duration, severity of motor symptoms and
      anti-parkinsonian medications, Glu but not Asp remained significantly associated
      with depression, along with Asp, GABA but not Glu remained negatively associated
      with sleep disturbances. The altered plasma levels of amino acids may be
      implicated in the pathogenesis of NMS of PD. 

PMID- 25059458
TI  - The healing effect of over-the-counter wound healing agents applied under
      semiocclusive film dressing.

PMID- 25059459
TI  - Use of 1H-nuclear magnetic resonance to screen a set of biomarkers for monitoring
      metabolic disturbances in severe burn patients.
AB  - INTRODUCTION: To establish a plasma metabolomics fingerprint spectrum for severe
      burn patients and to use it to identify a set of biomarkers that could be used
      for clinical monitoring. METHODS: Twenty-one severe burn patients and three
      healthy control individuals were enrolled in this study, and the plasma samples
      from patients and healthy individuals were collected for nuclear magnetic
      resonance (NMR) measurements. The NMR spectra were analyzed using principal
      component analysis (PCA) and partial least squares (PLS) in order to establish
      the metabolomics fingerprint representing the changes in metabolism and to select
      the major biomarkers. RESULTS: NMR spectra of the plasma samples showed
      significant differences between burn patients and healthy individuals. Using
      metabolomics techniques, we found an Eigen-metabolome that consists of 12
      metabolites, which are regulated by 103 enzymes in a global metabolic network.
      Among these metabolites, alpha-ketoisovaleric acid, 3-methylhistidine, and beta
      hydroxybutyric acid were the most important biomarkers that were significantly
      increased during the early stage of burn injury. These results suggest that the
      mitochondrial damage and carbohydrate, protein and fatty acid metabolism
      disturbances occur after burn injury. Our analysis also show that histone
      deacetylases, which are protein transcription suppressors, were remarkably
      increased and indicate that protein transcription was inhibited and anabolism was
      restrained during the early stage of burn injury. CONCLUSIONS: Metabolomics
      techniques based on NMR can be used to monitor metabolism in severe burn
      patients. Our study demonstrates that integrated 1H-NMR metabolome and global
      metabolic network analysis is useful for visualizing complex metabolic
      disturbances after severe burn injury and may provide a new quantitative injury
      severity evaluation for future clinical use. TRIAL REGISTRATION: Chinese Clinical
      Trial Registry ChiCTR-OCC-12002145. Registered 25 April 2012.

PMID- 25059461
TI  - Intentional examination of esophagus by narrow-band imaging endoscopy increases
      detection rate of cervical inlet patch.
AB  - Foci of heterotopic gastric mucosa have been identified at different sites in the
      human body and the most common location is the proximal esophagus which is
      referred to as cervical inlet patch (CIP). The true prevalence of CIP varies and
      it is usually incidental findings during endoscopy. Because CIP is always
      asymptomatic, it was believed to be of little clinical relevance. However,
      emerging studies have described the acid-secreting characteristics of heterotopic
      gastric mucosa and associations of CIP with gastroesophageal reflux disease
      (GERD). In addition, complications such as stricture, fistula, infection, mucosal
      hyperplasia, and malignant transformation have been reported. In this study, we
      investigated the prevalence of CIP, its associations with clinical
      manifestations, and the effect of intentional screening upper esophagus by
      magnifying endoscopy-narrow-band imaging (ME-NBI) system. Consecutive healthy
      adults who underwent panendoscopy were separated into two groups. Patients in
      group I (n = 471) were examined by an endoscopist who intended to find CIPs by ME
      NBI. Patients in group II (n = 428) were examined by two endoscopists who were
      unaware of the study and performed white-light imaging endoscopy. Participants
      provided questionnaires on GERD-related symptoms. Higher CIP prevalence (11.7%
      vs. 1.9%, P < 0.0001) and longer duration of esophageal examination (mean +/-
      standard deviation, 17.50 +/- 12.40 vs. 15.24 +/- 10.78 seconds, P = 0.004) were
      noted in group I than in group II. Analyzing group I patients revealed the higher
      prevalences of reflux symptoms (32.7% vs. 18.3%, P = 0.013) and erosive
      esophagitis (43.6% vs. 25.5%, P = 0.005) in patients with CIP than in those
      without. CIP was not associated with globus or dysphagia symptoms. More small
      CIPs (< 5 mm) were detected by ME-NBI than by white-light imaging (85.3% vs.
      41.4%, P = 0.001). In conclusion, CIP prevalence was not low under intentional ME
      NBI examination of the upper esophagus. The clinical relevance of CIP and its
      association with GERD require further investigation.

PMID- 25059460
TI  - Effectiveness of strengthened stimulation during acupuncture for the treatment of
      allergic rhinitis: study protocol for a randomized controlled trial.
AB  - BACKGROUND: The traditional Chinese theory of acupuncture emphasizes that the
      intensity of acupuncture must reach a threshold to generate de qi (a specific and
      compound sensation during the acupuncture), which is necessary to achieve the
      best therapeutic effect. However, the notion that de qi must be achieved for
      maximum benefit has not been confirmed by modern scientific evidence. This study
      aims to compare the efficacy of acupuncture with either strong (intended to
      elicit de qi) or weak stimulation among patients with allergic rhinitis.
      METHODS/DESIGN: This study compares real versus sham acupuncture in 140 patients
      with a history of persistent allergic rhinitis (PER) or intermittent allergic
      rhinitis (IAR) and with a positive skin prick test (SPT). The trial will be
      conducted in the Teaching Hospital of Chengdu University of Traditional Chinese
      Medicine (China). In the study, patients will be randomly assigned into two
      groups by computer-generated randomization and assessed prior to treatment. They
      will then receive 12 sessions of treatments for 4 consecutive weeks and have a
      follow-up phase lasting 12 weeks. The main outcome measures include the primary
      and secondary indicators. Primary indicators are subjective symptoms scores as
      evaluated by visual analogue scales (VAS), rhinoconjunctivitis quality of life
      questionnaires (RQLQ), and the Modified Massachusetts General Hospital
      acupuncture sensation scale, Chinese version (C-MMASS). The secondary indicators
      are the results of laboratory examinations, such as serum allergen-specific
      immunoglobulin E (sIgE) nasal inflammatory cells counts (mast cells, eosinophils,
      and T cells), and nitric oxide concentration in nasal excretion. The use of anti
      allergic medication will also be recorded as one of the secondary indicators.
      Furthermore, adverse events will be recorded and analyzed. Intention-to-treat
      analysis (ITT) and per-protocol (PP) analysis will be performed to test and
      verify the results in this trial. DISCUSSION: The results of this trial will
      demonstrate the efficacy of using acupuncture to treat allergic rhinitis and
      verify whether the effectiveness of acupuncture is related to the needle
      sensation de qi. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC
      13003594 (registered on 16 August 2013, and the first patient was randomized on
      27 September 2013).

PMID- 25059462
TI  - Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile
      dysfunction.
AB  - The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile
      signalling was assessed. Ten control male rats and 50 diabetic male rats were
      used and divided into the following: diabetic (DM), curcumin (CURC), NCD,
      tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene
      expression of heme oxygenase-1 (HO-1), Nrf2, NF-B and p38, enzyme activities of
      heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal
      pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12
      weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the
      significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme
      activities, a significant decrease in HO-1 gene and a significant increase in NF
      ?beta, p38 genes. Administration of all therapeutic interventions led to a
      significant increase in ICP/MAP, cGMP levels, a significant increase in HO-1 and
      NOS enzymes, a significant increase in HO-1, and Nrf2 gene expression, and a
      significant decrease in NF-?beta, p38 gene expression. NCD or its combination
      with tadalafil showed significant superiority and more prolonged duration of
      action. In conclusion, a tendency was observed that CURC and NCD have high
      efficacy and more prolonged duration of action in enhancing erectile function.

PMID- 25059463
TI  - Early and repeated IgG1Fc-pCons chimera vaccinations (GX101) improve the outcome
      in SLE-prone mice.
AB  - A previous study showed that a tolerogenic gene vaccine based on a IgG1Fc-pCons
      chimera (here named GX101) protects NZB/NZW mice from SLE development. The
      present study was aimed at identifying the most effective schedule of
      immunization and the possible involvement of CD4(+) Foxp3(+) Treg in the
      mechanism of action, in view of its eventual translation to the human studies.
      NZB/NZW mice were vaccinated with B lymphocytes made transgenic by spontaneous
      transgenesis with a gene coding for a chimeric IgG1Fc-pCons construct. Different
      schedules of vaccination were set in relation to the timing and number of
      administrations. Survival, proteinuria levels, and CD4(+) Foxp3(+) Treg frequency
      were monitored during the full experiments. GX101-treated mice showed delayed
      disease onset and delayed mortality than controls. GX101 effects were implemented
      by early as well as repeated vaccine administrations. GX101 vaccination was
      associated with increased frequencies of CD4(+) CD25(+) Foxp3(+) Treg with
      respect to controls. This study demonstrates that early and repeated
      immunizations with GX101 vaccine provide a better outcome than late or single
      vaccine administration regarding onset/development in SLE-prone mice, acting as a
      possible disease-modifying approach. Vaccine effects are likely related to CD4(+)
      Foxp3(+) Treg cell expansion. 

PMID- 25059464
TI  - Recent advances in visualizing vulnerable plaque: focus on noninvasive molecular
      imaging.
AB  - Traditional imaging methods in atherosclerosis have focused primarily on anatomic
      information. Imaging approaches that visualize molecular targets rather than
      anatomic structures may emphasize biologic aspects of atherosclerosis. Molecular
      imaging of atherosclerotic lesions has become a crucial experimental tool and is
      now emerging in the clinical arena. In this review, we briefly highlight the
      rationale and fundamental principles of molecular imaging. We then discuss the
      promising imaging modalities, along with their potential limitations, and the
      molecular targets being investigated in experimental research. Finally, we
      summarize the most important clinical studies recently performed in humans. 

PMID- 25059465
TI  - Catheter ablation for premature ventricular contractions and ventricular
      tachycardia in patients with heart failure.
AB  - Ventricular arrhythmias (VA) are a significant contributor to morbidity and
      mortality in patients with heart failure (HF). Implantable cardioverter
      defibrillators are effective in reducing mortality, but do not prevent arrhythmia
      recurrence. There is increasing recognition that frequent premature ventricular
      contractions or repetitive ventricular tachycardia may also lead to new onset
      ventricular dysfunction or deterioration of ventricular function in patients with
      pre-existing HF. Suppression of the arrhythmia may lead to recovery of
      ventricular function. Catheter ablation has emerged as a safe and effective
      treatment option for reducing arrhythmia recurrence and for suppression of PVCs
      but its efficacy is governed by the nature of the arrhythmias, the underlying HF
      substrate and the accessibility of the arrhythmia substrates to ablation. 

PMID- 25059466
TI  - Migraine and the risk for stroke and cardiovascular disease.
AB  - Numerous data have pointed to an association between migraine and cardiovascular
      diseases. The majority of the available data have indicated that migraine with
      aura can be considered a risk factor for ischemic stroke, whereas migraine
      without aura cannot be reliably considered as such. High frequency of attacks and
      a recent onset of migraine have been related to an increased ischemic stroke
      risk. In addition, in young subjects with ischemic stroke migraine with aura
      represents an independent risk factor of overall recurrent vascular events and of
      recurrent ischemic stroke. Also the risk of transient ischemic attack seems to be
      increased in migraineurs, although this issue has not been extensively
      investigated. Several studies have also addressed the possible association
      between migraine and hemorrhagic stroke. Although the results of these individual
      studies were conflicting, their meta-analysis showed that migraine is associated
      with a 1.5-fold increase in the risk of hemorrhagic stroke (including
      intracerebral and subarachnoid hemorrhage). Some studies have identified migraine
      also as a possible risk factor for cardiac vascular events while others have
      yielded negative results. A meta-analysis did not show an increased risk of
      myocardial infarction in subjects with any migraine vs no migraine but
      subsequently, data has pointed to an association between any migraine with
      cardiac ischemic disease. Migraine has also been associated by some studies with
      vascular mortality and with vascular diseases in regions other than the brain and
      the heart. Several studies have also indicated that compared with nonmigraineurs,
      migraineurs have a higher burden of asymptomatic white matter brain lesions and,
      according to some studies, also infarct-like lesions at brain magnetic resonance.
      The mechanisms underlying the relationship between migraine and cardiovascular
      disease are still unclear. The possible explanation may rely on a peculiar
      vascular vulnerability of migraineurs that may contribute to the pathogenesis of
      migraine and, in the presence of some other unknown factors may also contribute,
      over time, to the development of cardiovascular disease. At the moment, there are
      no reliable features that may indicate which subjects, across the overall
      migraine population, will develop vascular events and so far, no drugs are
      recommended for the vascular prevention in migraineurs unless other clear
      indications are present. In general, the acute treatment and the secondary
      prevention measures of a patient with stroke who has a history of migraine do not
      differ from that of other stroke patients. There is currently no direct evidence
      to support that a migraine prophylactic treatment will reduce future stroke risk
      in secondary prevention. 

PMID- 25059467
TI  - Perceptions about the acceptability and prevalence of HIV testing and factors
      influencing them in different communities in South Africa.
AB  - HIV counselling and testing (HCT) is considered important because it is an entry
      point to a comprehensive continuum of care for HIV/AIDS. The South African
      Department of Health launched an HCT campaign in April 2010, and this reached
      13,269,746 people by June 2011, of which 16% tested HIV positive and 400,000 of
      those were initiated into antiretroviral treatment. The overall objective of this
      project was to gain insight into the general perceptions about HIV testing in the
      different South African communities. Factors influencing testing in these
      communities were also explored. Discussions with twelve focus groups (FG) of 8-12
      participants each were conducted with male and female participants recruited from
      both urban formal and informal communities in Cape Town and Durban. Participants
      included four racial groups represented by different age groups as follows:
      adolescents (12-17 years), youth (18-24 years) and adults (25 years and older).
      Data were analyzed using thematic coding. Among the key themes that emerged from
      the findings were the inaccurate perception of risk, fear of testing HIV
      positive, stigma and discrimination. Participants from both African and Indian
      FGs reported being less likely to do self-initiated HIV testing and counselling,
      while those from the FG consisting of young whites were more likely to learn
      about their HIV status through blood donations and campus HIV testing campaigns.
      Most FGs said they were likely to test if they understood the testing process
      better and also if the results are kept confidential. The present findings
      reiterate the importance of spreading positive messages and ensuring
      confidentiality for HIV testing in a society where there is still some stigma
      associated with people living with HIV/AIDS. This can partly be accomplished by
      the continuation of the national HCT campaign, which has been a considerable
      success in the fight against HIV/AIDS in South Africa during the past two years.

PMID- 25059468
TI  - Evidence for biological denitrification inhibition (BDI) by plant secondary
      metabolites.
AB  - Previous studies on the effect of secondary metabolites on the functioning of
      rhizosphere microbial communities have often focused on aspects of the nitrogen
      (N) cycle but have overlooked biological denitrification inhibition (BDI), which
      can affect plant N-nutrition. Here, we investigated the BDI by the compounds of
      Fallopia spp., an invasive weed shown to be associated with a low potential
      denitrification of the soil. Fallopia spp. extracts were characterized by
      chromatographic analysis and were used to test the BDI effects on the metabolic
      and respiratory activities of denitrifying bacteria, under aerobic and anaerobic
      (denitrification) conditions. The BDI of Fallopia spp. extracts was tested on a
      complex soil community by measuring denitrification enzyme activity (DEA),
      substrate induced respiration (SIR), as well as abundances of denitrifiers and
      total bacteria. In 15 strains of denitrifying bacteria, extracts led to a greater
      BDI (92%) than respiration inhibition (50%). Anaerobic metabolic activity
      reduction was correlated with catechin concentrations and the BDI was dose
      dependent. In soil, extracts reduced the DEA/SIR ratio without affecting the
      denitrifiers: total bacteria ratio. We show that secondary metabolite(s) from
      Fallopia spp. inhibit denitrification. This provides new insight into plant-soil
      interactions and improves our understanding of a plant's ability to shape
      microbial soil functioning.

PMID- 25059469
TI  - Retraction statement. Retraction: A novel rat model of cardiopulmonary bypass for
      deep hypothermic circulatory arrest without blood priming. Chin Med J 2014; 127
      (7): 1317-20.

PMID- 25059470
TI  - Retraction: A novel, minimally invasive rat model of normothermic cardiopulmonary
      bypass model without blood priming. Chin Med J 2014; 127 (8): 1541-4.

PMID- 25059471
TI  - Pain referents used to respond to the pain catastrophizing scale.
AB  - BACKGROUND: Pain catastrophizing has emerged as a highly important construct in
      pain research. The Pain Catastrophizing Scale (PCS) is a widely used self-report
      measure used to determine a person's level of pain catastrophizing, assumed to be
      associated with an ongoing, recalled or anticipated pain experience. In practice,
      instructions for self-reporting catastrophizing typically do not provide a
      specific pain referent, even when assessing patients with chronic pain.
      Researchers have noted that it is not known what type of pain participants are
      referring to when responding to a catastrophizing questionnaire. METHOD: In the
      current study, 182 presumably healthy undergraduate students completed the PCS
      followed by a query regarding the pain referent used to complete the scale. In
      addition, they were asked if they have ever experienced chronic pain and to list
      their worst pain experience. RESULTS: The most commonly used primary referents
      included pain due to acute injury (26.4%), headache (18.0%) and general physical
      pain (11.5%). The type of primary referent and the number of referents did not
      influence the catastrophizing scores. However, the catastrophizing scores were
      influenced by the context of the primary pain referent, i.e., whether the primary
      pain referent was non-chronic worst pain, both chronic and worst pain, chronic
      pain or unrelated to either chronic or worst pain. Notably, a larger than
      expected proportion of participants reported having experienced chronic pain
      (44.5%; n = 81). CONCLUSION: The examination of pain referents while responding
      to a catastrophizing measure would add to our understanding of a person's pain
      experience and related catastrophic cognitions.

PMID- 25059472
TI  - miR-101 promotes breast cancer cell apoptosis by targeting Janus kinase 2.
AB  - AIMS: microRNA-101 (miR-101) is down-regulated in several cancers. In this study,
      we explored the effects of dysregulated miR-101 on breast cancer cells and the
      underlying mechanisms. METHODS: miR-101 level was quantified by real-time RT-PCR.
      Cell viability was analyzed by MTT assay. Apoptosis was detected by flow
      cytometry and TUNEL assay. Moreover, the level of protein expression was
      determined by Western blot. RESULTS: miR-101 level was markedly reduced in both
      the human breast cancer samples and cultured breast cancer cell lines (MCF-7, MDA
      MB-231). Overexpression of miR-101 inhibited the proliferation and promoted the
      apoptosis in cultured MCF-7 and MDA-MB-231 cells, which were reversed by co
      transfection of AMO-101, the inhibitor of miR-101. We validated Janus kinase 2
      (Jak2) as a direct target of miR-101. Knockdown of Jak2 induced apoptosis in
      cultured breast cancer cells. Moreover, the level of miR-101 is negatively
      correlated with Jak2 in breast cancer tissues and cell lines. CONCLUSIONS: miR
      101 suppressed proliferation and promoted apoptosis in breast cancer cells by
      targeting Jak2. These findings indicate that manipulation of miR-101 expression
      may represent a novel therapeutic strategy in the treatment of breast cancer.

PMID- 25059474
TI  - Organ procurement from executed prisoners in China.
AB  - Organ procurement from executed prisoners in China is internationally condemned,
      yet this practice continues unabated in 2014. This is despite repeated
      announcements from Chinese authorities that constructive measures have been
      undertaken to conform to accepted ethical standards. While there is unanimous
      agreement on the unethical nature of using organs from executed prisoners, due to
      its limitations on voluntary and informed consent, there is insufficient coverage
      of forced organ procurement from prisoners of conscience without consent.
      Strategies to influence positive change in China over the last few decades have
      failed to bring this practice to an end. While organ donation and transplantation
      services in China have undergone considerable structural changes in the last few
      years, fundamental attempts to shift practice to ethically sourced organs have
      floundered. In this article, we discuss the organ trade in China, reflect upon
      organ procurement from executed prisoners (including both capital prisoners and
      prisoners of conscience) and provide an overview of contradictory Chinese efforts
      to halt forced organ procurement from executed prisoners. Finally, we highlight
      current actions being taken to address this issue and offer comprehensive
      recommendations to bring this ethically indefensible practice to an immediate
      end. 

PMID- 25059473
TI  - The necessity of and strategies for improving confidence in the accuracy of
      western blots.
AB  - Western blotting is one of the most commonly used laboratory techniques for
      identifying proteins and semi-quantifying protein amounts; however, several
      recent findings suggest that western blots may not be as reliable as previously
      assumed. This is not surprising since many labs are unaware of the limitations of
      western blotting. In this manuscript, we review essential strategies for
      improving confidence in the accuracy of western blots. These strategies include
      selecting the best normalization standard, proper sample preparation, determining
      the linear range for antibodies and protein stains relevant to the sample of
      interest, confirming the quality of the primary antibody, preventing signal
      saturation and accurately quantifying the signal intensity of the target protein.
      Although western blotting is a powerful and indispensable scientific technique
      that can be used to accurately quantify relative protein levels, it is necessary
      that proper experimental techniques and strategies are employed. 

PMID- 25059475
TI  - A new model for in vitro testing of vitreous substitute candidates.
AB  - PURPOSE: To describe a new model for in vitro assessment of novel vitreous
      substitute candidates. METHODS: The biological impact of three vitreous
      substitute candidates was explored in a retinal explant culture model; a
      polyalkylimide hydrogel (Bio-Alcamid(r)), a two component hydrogel of 20 wt.%
      poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked
      sodium hyaluronic acid hydrogel (Healaflow(r)). The gels where applied to
      explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel
      exposed explants were compared with explants incubated under standard tissue
      culture conditions. Cryosections of the specimens were stained with hematoxylin
      and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC,
      Rhodopsin) and TUNEL. RESULTS: Explants kept under standard conditions as well as
      PEG-exposed explants displayed disruption of retinal layers with moderate
      pyknosis of all neurons. They also displayed moderate labeling of apoptotic
      cells. Bio-Alcamid(r)-exposed explants displayed severe thinning and disruption
      of retinal layers with massive cell death. Healaflow(r)-treated explants
      displayed normal retinal lamination with significantly better preservation of
      retinal neurons compared with control specimens, and almost no signs of
      apoptosis. Retinas exposed to Healaflow(r) and retinas kept under standard
      conditions showed variable labeling of GFAP with generally low expression and
      some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling
      and Bio-Alcamid(r)-exposed retinas showed sparse labeling of GFAP. CONCLUSIONS:
      Research into novel vitreous substitutes has important implications for both
      medical and surgical vitreoretinal disease. The in vitro model presented here
      provides a method of biocompatibility testing prior to more costly and cumbersome
      in vivo experiments. The explant culture system imposes reactions within the
      retina including disruption of layers, cell death and gliosis, and the
      progression of these reactions can be used for comparison of vitreous substitute
      candidates. Bio-Alcamid(r) had strong adverse effects on the retina which is
      consistent with results of prior in vivo trials. PEG gel elicits reactions
      similar to the control retinas whereas Healaflow(r) shows protection from culture
      induced trauma indicating favorable biocompatibility.

PMID- 25059477
TI  - Tungsten carbide-nitride on graphene nanoplatelets as a durable hydrogen
      evolution electrocatalyst.
AB  - Alternatives to platinum-based catalysts are required to sustainably produce
      hydrogen from water at low overpotentials. Progress has been made in utilizing
      tungsten carbide-based catalysts, however, their performance is currently limited
      by the density and reactivity of active sites, and insufficient stability in
      acidic electrolytes. We report highly active graphene nanoplatelet-supported
      tungsten carbide-nitride nanocomposites prepared via an in situ solid-state
      approach. This nanocomposite catalyzes the hydrogen evolution reaction with very
      low overpotential and is stable operating for at least 300 h in harsh acidic
      conditions. The synthetic approach offers a great advantage in terms of
      structural control and kinetics improvement.

PMID- 25059476
TI  - The retinal pigment epithelium (RPE) induces FasL and reduces iNOS and Cox2 in
      primary monocytes.
AB  - PURPOSE: Retinal pigment epithelium (RPE) cells may alter the phenotype of
      monocytes by soluble factors that may be influenced by stimulation of the RPE.
      Since RPE cells carry the toll-like receptor-3 (TLR3) that detects and reacts to
      viral infection through binding of dsRNA we investigated the effects of RPE cells
      with or without TLR3 stimulation on blood-derived monocytes with respect to
      regulation of pro-/anti-inflammatory cytokines, anti-angiogenic factors and
      migratory properties. METHODS: Primary RPE cells were prepared from porcine eyes;
      monocytes were prepared from porcine blood. TLR3 activation was induced by
      polyinosinic:polycytidylic acid (Poly I:C). RPE cells were stimulated with Poly
      I:C in different concentrations for 24 hours and a cell culture supernatant was
      applied to the monocytes. Expression of CD14 and Fas ligand (FasL) was determined
      via flow cytometry. The expression of IL-6, IL-1beta, TNFalpha, Cox2, iNOS and IL
      10 was determined via quantitative RT-PCR. Migration was determined using Boyden
      chamber experiments. RESULTS: The supernatant of RPE cells, irrespective of TLR3
      activation, induced FasL expression in the monocytes. Expression of iNOS and Cox2
      was reduced by RPE cells and the reduction of Cox2 but not if iNOS was lost under
      TLR3 activation. No induction of IL-6, IL-1beta, IL-10 or TNFalpha by the RPE was
      seen. TLR3-activated RPE cells induced monocyte migration. CONCLUSION: RPE cells
      induce an upregulation of FasL and a downregulation of iNOS and Cox2 without
      upregulating inflammatory cytokines, possibly inducing an anti-angiogenic
      phenotype in the monocytes. This phenotype is still upheld after challenging RPE
      cells with dsRNA, mimicking a viral infection.

PMID- 25059480
TI  - Macroporous Fe3O4/carbon composite microspheres with a short Li+ diffusion
      pathway for the fast charge/discharge of lithium ion batteries.
AB  - Macroporous Fe3O4/carbon composite and core-shell Fe3O4@carbon composite
      microspheres have been prepared by means of one-pot spray pyrolysis. The addition
      of polystyrene (PS) nanobeads to a spray solution containing an iron salt and
      poly(vinylpyrrolidone) (PVP) led to macroporous Fe3O4/carbon composite
      microspheres, the carbon and iron components of which are uniformly distributed
      over the entire composite microsphere. The pore-size distribution curve for the
      macroporous Fe3O4/carbon composite shows distinct peaks at around 10 and 80 nm.
      An electrode prepared from the macroporous Fe3O4/carbon composite microspheres
      showed better cycling and rate performances than an electrode formed from core
      shell Fe3O4@carbon composite microspheres. The initial discharge and charge
      capacities of the macroporous Fe3O4/carbon composite microsphere electrode were
      determined to be 1258 and 908 mA h g(-1) at 2 A g(-1), respectively, and the
      corresponding initial coulombic efficiency was 72 %. The composite microsphere
      electrode cycled 500 times at 5 A g(-1) showed a high discharge capacity of 733
      mA h g(-1).

PMID- 25059478
TI  - Evaluation of transmission risks associated with in vivo replication of several
      high containment pathogens in a biosafety level 4 laboratory.
AB  - Containment level 4 (CL4) laboratories studying biosafety level 4 viruses are
      under strict regulations to conduct nonhuman primate (NHP) studies in compliance
      of both animal welfare and biosafety requirements. NHPs housed in open-barred
      cages raise concerns about cross-contamination between animals, and accidental
      exposure of personnel to infectious materials. To address these concerns, two NHP
      experiments were performed. One examined the simultaneous infection of 6 groups
      of NHPs with 6 different viruses (Machupo, Junin, Rift Valley Fever, Crimean
      Congo Hemorrhagic Fever, Nipah and Hendra viruses). Washing personnel between
      handling each NHP group, floor to ceiling biobubble with HEPA filter, and
      plexiglass between cages were employed for partial primary containment. The
      second experiment employed no primary containment around open barred cages with
      Ebola virus infected NHPs 0.3 meters from naive NHPs. Viral antigen-specific
      ELISAs, qRT-PCR and TCID50 infectious assays were utilized to determine antibody
      levels and viral loads. No transmission of virus to neighbouring NHPs was
      observed suggesting limited containment protocols are sufficient for multi-viral
      CL4 experiments within one room. The results support the concept that Ebola virus
      infection is self-contained in NHPs infected intramuscularly, at least in the
      present experimental conditions, and is not transmitted to naive NHPs via an
      airborne route. 

PMID- 25059481
TI  - An improved method for guinea pig airway smooth muscle cell culture and the
      effect of SPFF on intracellular calcium.
AB  - The aim of the present study was to establish an improved method for in vitro
      guinea pig airway smooth muscle (ASM) cell culture and to evaluate the effect of
      2-(4-amino-3-chloro-5-trifluomethyl-phenyl)-2-tert-butylamino-ethanol
      hydrochloride (SPFF), a novel beta2-adrenoceptor agonist, on the release of
      intracellular calcium in cells. A procedure for the efficient isolation, culture,
      passage and characterization of the cells was described. Primary ASM cells of
      guinea pigs were cultured by modified tissue cultivation. The cells were
      identified by their morphological characteristics and immunocytochemistry. The
      relative inhibition of the release of intracellular calcium by drugs in the cells
      was measured by fluorometric quantification with fluorochrome Fura-2/AM. The
      results were as follows: a) The ASM cells of the guinea pigs were successfully
      cultured and subcultured by using our improved method and typical peak-valley
      characteristics were observed under the phase contrast microscope; b) data from
      immunocytochemical staining with specific alpha-smooth muscle actin (alpha-SMA)
      demonstrated that the cells were ASM cells; c) the growth characteristics and
      cell viability demonstrated that the cells were in good condition and were able
      to be applied in the follow-up studies; d) the inhibitory effect of SPFF on the
      release of intracellular calcium was concentration-dependent when compared with
      the control and e) the potential mechanisms of SPFF on the inhibition of
      intracellular calcium may be independent of the ryanodine receptor, but may be
      closely associated with the inositol 1,4,5-trisphosphate receptor.

PMID- 25059482
TI  - Different TP53 mutations are associated with specific chromosomal rearrangements,
      telomere length changes, and remodeling of the nuclear architecture of telomeres.
AB  - TP53 mutations are the most common mutations in human cancers, and TP53-R175H and
      TP53-R273H are the most frequent. The impact of these mutations on genomic
      instability after tumor initiation is still uncovered. To gain insight into this,
      we studied the effects of three specific TP53 mutants (TP53-V143A, TP53-R175H,
      and TP53-R273H) on genomic instability using four isogenic lines of LoVo cells.
      Multicolor fluorescence in situ hybridization (FISH), three-dimensional (3D)
      quantitative FISH (Q-FISH) on interphase and Q-FISH on metaphases were used to
      investigate genomic instability. We found that LoVo cells expressing mutant TP53
      R175H displayed the highest level of chromosomal instability among the LoVo cell
      lines. Furthermore, we observed that mutant TP53-R175H and TP53-V143A showed more
      alterations in their 3D nuclear architecture of telomeres than the mutant TP53
      R273H and the wild type. Moreover, we noted an association between some
      chromosomal abnormalities and telomere elongation in the mutant TP53-R175H. Taken
      together, our results indicate that the mutation TP53-R175H is more likely to
      cause higher levels of genomic instability than the other TP53 mutations. We
      proposed that the type of TP53 mutations and the genetic background of a cancer
      cell are major determinants of the TP53-dependent genomic instability.

PMID- 25059484
TI  - Cleavage pattern and development of isolated D blastomeres in bivalves.
AB  - Although bivalves develop through spiral cleavage patterns, similar to other
      lophotrochozoans, the cleavage pattern of D lineage blastomeres is unique, since
      2d shows four rounds of stereotypic unequal cleavage before bilateral cleavage of
      the largest derivative of 2d: 2d(1121) . This unique modification of spiral
      cleavage is directly associated with the characteristic morphology of bivalves,
      namely, bilaterally separated shell plates, because the bilateral shell plates
      are thought to be derived from the bilateral derivatives of 2d(1121) . In this
      report, to determine whether the unique cleavage pattern of bivalves is regulated
      depending on the interaction with other cells or by cell autonomous mechanisms,
      we performed cell isolation experiments and observed subsequent cleavage patterns
      of isolated blastomeres. When focusing on the largest derivatives of D
      blastomeres, 8% of isolated D blastomeres followed the cleavage pattern of normal
      development up to bilateral cleavage. Importantly, the remainder of the partial
      embryos ended cleavage before that stage, and none of the isolated blastomeres
      showed abnormal cleavage patterns. We also examined the development of isolated
      blastomeres and found that isolated D blastomeres could develop shell plates,
      whereas larvae developed from AB blastomeres never had shell plates. Based on
      these observations, we concluded that D blastomeres control their unique cleavage
      pattern through intrinsic mechanisms and develop shell glands autonomously
      without any cell-cell interaction with other lineages.

PMID- 25059483
TI  - Genetic variation in melatonin pathway enzymes in children with autism spectrum
      disorder and comorbid sleep onset delay.
AB  - Sleep disruption is common in individuals with autism spectrum disorder (ASD).
      Genes whose products regulate endogenous melatonin modify sleep patterns and have
      been implicated in ASD. Genetic factors likely contribute to comorbid expression
      of sleep disorders in ASD. We studied a clinically unique ASD subgroup,
      consisting solely of children with comorbid expression of sleep onset delay. We
      evaluated variation in two melatonin pathway genes, acetylserotonin O
      methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher
      frequencies than currently reported (p < 0.04) for variants evidenced to decrease
      ASMT expression and related to decreased CYP1A2 enzyme activity (p <= 0.0007). We
      detected a relationship between genotypes in ASMT and CYP1A2 (r(2) = 0.63). Our
      results indicate that expression of sleep onset delay relates to melatonin
      pathway genes.

PMID- 25059485
TI  - Reduced plasma corticotropin-releasing hormone levels during late gestation in
      patients with intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) may lead to sudden onset
      of stillbirth, which most likely is related to uteroplacental insufficiency and
      dysregulation of the fetal blood supply. The relaxing effect of corticotropin
      releasing hormone (CRH) on blood vessels was measured to examine the role of CRH
      in the pathogenesis of ICP. METHODS: Eighty normal pregnant women and 80 ICP
      patients were divided into four groups of 20 cases, respectively, each based on
      gestational age from week 34 to 37. Radioimmunoassay was used to measure CRH in
      plasma samples collected from all of the subjects. RESULTS: Plasma CRH increased
      markedly from week 34 to 37 in both ICP and healthy patients, but the increase
      was lower in the ICP group. Plasma CRH was 322 +/- 61 pg/ml in mild ICP cases at
      37 weeks' compared to 1,066 +/- 173 pg/ml in controls (p < 0.05), but only 218 +/
      128 pg/ml in severe ICP (p < 0.05). Plasma CRH was significantly lower at all
      other measured time points in patients with severe ICP. In ICP patients, there
      was a negative correlation between plasma CRH and total bile acid (TBA).
      CONCLUSION: A limited increasing CRH level and negative correlation of CRH with
      TBA were unveiled in ICP patients.

PMID- 25059486
TI  - Placental hematoma mimicking twin anemia-polycythemia sequence following
      selective laser photocoagulation for twin-twin transfusion syndrome.

PMID- 25059487
TI  - Measuring educational needs among patients with systemic lupus erythematosus
      (SLE) using the Dutch version of the Educational Needs Assessment Tool (D-ENAT).
AB  - OBJECTIVE: The Educational Needs Assessment Tool (ENAT) was developed in the
      United Kingdom (UK) to systematically assess the educational needs of patients
      with rheumatic diseases. The aim of the present study was to describe the
      educational needs of Dutch patients with systemic lupus erythematosus (SLE) by
      means of a Dutch version of the ENAT (D-ENAT). METHODS: The D-ENAT was sent to a
      random sample of 244 SLE patients registered at the outpatient clinic of a
      university hospital. D-ENAT consists of 39 items in seven domains. The D-ENAT
      domain scores range from 0-16 to 0-28 (higher scoring equals higher educational
      needs) depending of the number of items in the domain. A total D-ENAT score (0
      156) is calculated by summing all 39 items. In addition, age, disease duration,
      gender, educational level, present information need (yes/no) and the extent of
      information need (1-4: nothing-everything) were recorded. Univariate regression
      analysis was used to examine the D-ENAT's potential determinants. RESULTS: The
      response rate was 122 out of 244 (50%). The mean (% of maximum score) educational
      needs scores were 56% for 'D-ENAT total score', 62% for 'Self-help measures', 60%
      for 'Disease process', 58% for 'Feelings', 56% for 'Treatments', 50% for
      'Movement', 49% for 'Support systems' and 46% for 'Managing pain'. Being female
      was significantly associated with higher scoring on the D-ENAT total score (beta
      23.0; 95% CI 5.9, 40.3). CONCLUSION: SLE patients demonstrated substantial
      educational needs, especially in the domains: 'Self-help measures', 'Disease
      process' and 'Feelings'. The validity and practical applicability of the D-ENAT
      to make an inventory of SLE patients' educational needs requires further
      investigation.

PMID- 25059488
TI  - Carotid subclinical atherosclerosis is associated with disease activity but not
      vitamin D in Korean systemic lupus erythematosus.
AB  - Atherosclerosis develops early in systemic lupus erythematosus (SLE) patients and
      is an important cause of mortality. Vitamin D deficiency is found to be
      associated with cardiovascular disease and autoimmunity. We evaluated the extent
      of carotid subclinical atherosclerosis and analyzed its correlation with vitamin
      D in SLE. One hundred and two female patients with SLE and 52 normal controls
      (NCs) were recruited. The mean carotid intima-media thickness (IMT) of SLE
      patients was 0.41 +/- 0.08 mm, which was higher than that of NCs (0.32 +/- 0.08
      mm, p = 0.012). In addition, carotid plaques were more frequent and the plaque
      index was higher in SLE patients than in NCs (0.68 +/- 1.39 vs. 0.26 +/- 0.87, p
      = 0.026). Carotid IMT was correlated with age, body mass index, SLE disease
      activity index, and aspirin use in SLE patients. The plaque index was correlated
      with renal involvement. Vitamin 25(OH)D3 level was not correlated with carotid
      IMT, plaque index or disease activity markers. In SLE, the risk of cardiovascular
      disease is higher than that in NCs, which may be derived from systemic
      inflammation. It may be not suitable to assess vitamin D as a marker of disease
      activity or subclinical atherosclerosis in SLE patients.

PMID- 25059489
TI  - Adalimumab-induced lupus panniculitis.

PMID- 25059490
TI  - Systemic lupus erythematosus patients in the low-latitude plateau of China:
      altitudinal influences.
AB  - The current study was to investigate the features of hospitalized patients with
      systemic lupus erythematosus (SLE) at different altitudes. The correlation
      between SLE activity and altitudinal variations was also explored. Medical
      records of 1029 patients were retrospectively reviewed. Activity of SLE in each
      organ system was recorded using the Systemic Lupus Erythematosus Disease Activity
      Index (SLEDAI). There was no significant correlation between SLE activity and
      altitudes (r = 0.003, p = 0.159). Age at onset for SLE patients at high altitudes
      was significantly younger than that at low and moderate altitudes (p = 0.022 and
      p = 0.004, respectively). Age at SLE admission at low altitudes was significant
      older than those at moderate and high altitudes (p = 0.011 and p < 0.001,
      respectively). Patients at high altitudes had shorter duration from disease onset
      to admission than those at moderate altitudes (p = 0.009). Incidence of Sm
      antibodies-positive for resident patients at high altitudes was 36.4%, which were
      higher than that at moderate altitudes (p = 0.003). We found increasing trends of
      CNS activity in active patients; immunological and renal activities in inactive
      patients were correlated with elevated altitudes (p = 0.024, p = 0.004, p =
      0.005), while arthritis scores in active patients showed the tendency of
      decreasing with the rise of elevation (p = 0.002). Hemoglobin level, red blood
      cell and platelet counts at high altitudes were significantly lower than those at
      low altitudes (p < 0.05, respectively). There was no significant difference in
      hemoglobin level between moderate- and low-altitude groups (p > 0.05). No
      significant difference in platelet counts between moderate- and high-altitude
      groups was observed (p > 0.05). Our findings suggest that some clinical features,
      laboratory tests and activity of main organs in SLE are influenced by altitudes.
      Furthermore, organ activities of active and inactive SLE patients have different
      patterns of altitudinal variations. These distinctive variations likely reveal
      that peculiar environmental factors at high altitudes can affect the development
      of SLE.

PMID- 25059491
TI  - Incidence and relevance of proteinuria in bevacizumab-treated patients: pooled
      analysis from randomized controlled trials.
AB  - BACKGROUND: This analysis evaluated the incidence of and risk factors for
      bevacizumab-related proteinuria and assessed for any associated clinical
      sequelae, including renal function changes. METHODS: Patient-level adverse event
      and laboratory data from a pooled safety database were used to characterize
      alterations in urine protein excretion following interventional therapy +/-
      bevacizumab in 17 randomized trials across multiple tumor types. Severity of
      renal function change was assessed using changes in serum creatinine
      concentration from baseline values. Potential predictors of proteinuria and the
      association between proteinuria and other adverse events were also investigated.
      RESULTS: Among 14,548 patients, the incidence of any-grade proteinuria was 8.2%
      (733/8,917) and 4.6% (257/5,631) in the bevacizumab and control groups,
      respectively; rates of grade >=3 proteinuria were 1.4 and 0.2%. Post-baseline
      proteinuria grade and bevacizumab were associated with increased rates of renal
      dysfunction. Patients developing proteinuria had an increased rate of any-grade
      infection but not thromboembolic events. History of diabetes was the only
      examined risk factor that appeared to have a significant association with
      proteinuria development. CONCLUSIONS: This analysis confirmed a significant
      increase in the development of proteinuria during bevacizumab treatment. We also
      observed an increased rate of renal dysfunction associated with bevacizumab
      treatment and among subjects with proteinuria, although the dysfunction was
      generally mild. The development of proteinuria was also associated with a modest
      increase in risk of infection.

PMID- 25059492
TI  - Concurrent oral human papilloma virus infection in patients with recurrent
      respiratory papillomatosis: a preliminary study.
AB  - OBJECTIVES/HYPOTHESIS: To determine oral human papilloma virus (HPV) colonization
      in patients with adult-onset recurrent respiratory papillomatosis (AO-RRP) and
      their long-term partners. STUDY DESIGN: Prospective, cohort study METHODS:
      Patients with pathology-confirmed AO-RRP and a small cohort of their long-term
      partners were subjected to a standardized oral rinse and swab protocol to obtain
      oral epithelial cells. DNA from these samples was extracted and subjected to both
      qualitative analyses via multiplex polymerase chain reaction as well as to a
      commercially available linear array assay for the determination of specific HPV
      subtypes. RESULTS: Samples were collected from 27 patients with AO-RRP and six
      long-term sexual partners. Qualitative analysis of agarose gel products using a
      multiple genotype primer cocktail suggested the presence of HPV DNA in oral rinse
      or swabs in 26 patients (96%) and four partner samples (67%). A subset of these
      positive patient samples was then subjected to genotyping; a spectrum of HPV
      subtypes was observed. Interestingly, HPV81 was identified in many samples.
      CONCLUSION: Recent data suggest that less than 7% of the general population is
      HPV positive in the oral cavity. Our data suggest that the oral colonization rate
      is much higher in patients with AO-RRP. Additionally, long-term sexual partners
      of patients with RRP had a much higher rate of HPV positivity. These preliminary
      data may have implications for viral transmission and provide a framework for
      enhanced patient education as well as further investigation. LEVEL OF EVIDENCE:
      4.

PMID- 25059493
TI  - Neuroendocrine regulation and homeostasis.

PMID- 25059494
TI  - Conditional inference trees: a method for predicting intimate partner violence.
AB  - A number of different methodologies have been employed to investigate the complex
      relationship between psychological and physical aggression. Herein, a method of
      unbiased recursive partitioning (conditional inference trees) was applied to a
      longitudinal sample to identify cutoffs of psychological aggression at baseline
      that differentiate between individuals who do and do not perpetrate physical
      aggression at follow-up. The algorithm categorized men into low- and high-risk
      groups, and women into mild-, moderate-, or high-risk categories of perpetration.
      Couples responded anonymously to a self-report measure of psychological and
      physical aggression (CTS2) at baseline and a 12-month follow-up. Sensitivity
      analyses for predicting physical aggression reached as high as 59% for women and
      60% for men. 

PMID- 25059495
TI  - Wolbachia endosymbiont of Brugia malayi elicits a T helper type 17-mediated pro
      inflammatory immune response through Wolbachia surface protein.
AB  - Wolbachia is an endosymbiotic bacterium of the filarial nematode Brugia malayi.
      The symbiotic relationship between Wolbachia and its filarial host is dependent
      on interactions between the proteins of both organisms. However, little is known
      about Wolbachia proteins that are involved in the inflammatory pathology of the
      host during lymphatic filariasis. In the present study, we cloned, expressed and
      purified Wolbachia surface protein (r-wsp) from Wolbachia and administered it to
      mice, either alone or in combination with infective larvae of B. malayi (Bm-L3)
      and monitored the developing immune response in infected animals. Our results
      show that spleens and mesenteric lymph nodes of mice immunized with either r-wsp
      or infected with Bm-L3 show increased percentages of CD4(+) T helper type 17
      (Th17) cells and Th1 cytokines like interferon-gamma and interleukin-2 (IL-2)
      along with decreased percentages of regulatory T cells, Th2 cytokines like IL-4
      and IL-10 and transforming growth factor beta (TGF-beta) levels in culture
      supernatants of splenocytes. These observations were stronger in mice immunized
      with r-wsp alone. Interestingly, when mice were first immunized with r-wsp and
      subsequently infected with Bm-L3, percentages of CD4(+) Th17 cells and Th1
      cytokines increased even further while that of regulatory T cells, Th2 cytokines
      and TGF-beta levels decreased. These results for the first time show that r-wsp
      acts synergistically with Bm-L3 in promoting a pro-inflammatory response by
      increasing Th17 cells and at the same time diminishes host immunological
      tolerance by decreasing regulatory T cells and TGF-beta secretion. 

PMID- 25059497
TI  - A novel method for classifying starch digestion by modelling the amylolysis of
      plant foods using first-order enzyme kinetic principles.
AB  - Studying starch amylolysis kinetics in vitro is valuable for predicting the
      postprandial glycaemic response to starch intake. Prediction of starch amylolysis
      behaviour is challenging however, because of the many physico-chemical factors
      which influence amylolysis. The Logarithm of Slope (LOS) method for analysis of
      digestibility curves using first-order enzyme kinetics can identify and quantify
      nutritionally important starch fractions. The early stages of in vitro amylolysis
      of hydrothermally processed chickpea and durum wheat with variable degrees of
      structural integrity were studied. The end-point product concentration
      (Cinfinity) and the pseudo first-order digestibility rate constant k, obtained
      from LOS analysis, were then used to compute predictive digestibility curves for
      evaluation of the model performance. LOS analysis enabled rapid identification of
      nutritionally important starch-fractions. It was clear that purified starches and
      flours were digested by a single-phase process, but starch amylolysis in
      macroparticles occurred by a two-phase system that reflected differences in
      substrate accessibility. The model gave an excellent fit to data obtained from a
      range of heterogeneous materials. It provides a rigorous means of studying the
      mechanisms of starch amylolysis in samples of varying complexity, and we strongly
      recommend its use for the rapid and accurate predictions of amylolysis. Such
      predictions have implications for prevention and management of type 2 diabetes
      mellitus and obesity. 

PMID- 25059496
TI  - Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL
      amyloidosis: a matched case-control study on 174 patients.
AB  - Oral melphalan and dexamethasone (MDex) is a standard treatment for patients with
      AL amyloidosis who are not eligible for stem cell transplantation at many
      referral centers. However, following encouraging reports on the activity of
      bortezomib combined with alkylators and dexamethasone, these combinations are
      being moved to frontline therapy. We compared the outcome of 87 patients treated
      with bortezomib plus MDex (BMDex) with that of 87 controls treated with MDex.
      Patients and controls were matched for age, cardiac and renal function and free
      light chain burden. A higher rate of complete responses was observed with BMDex
      (42 vs 19%), but this did not result in a survival improvement in the overall
      population. However, a significant survival advantage for BMDex was observed in
      patients without severe (New York Heart Association class III or IV) heart
      failure and with N-terminal pro-natriuretic peptide type-B <8500 ng/l. Patients
      treated with full-dose dexamethasone had similar response rates and survival
      whether they received bortezomib or not. Intermediate-risk patients who are not
      fit enough to receive high-dose dexamethasone are likely to take the greatest
      advantage from the addition of bortezomib to MDex. 

PMID- 25059498
TI  - Detection of fovea-threatening diabetic macular edema by optical coherence
      tomography to maintain good vision by prophylactic treatment.
AB  - BACKGROUND/AIMS: To establish a screening and treatment method for fovea
      threatening diabetic macular edema (DME) using spectral-domain optical coherence
      tomography (SD-OCT). In order to maintain good visual acuity (VA), focal/grid
      laser treatment for screened fovea-threatening DME was evaluated based on macular
      thickness map images produced by SD-OCT. METHODS: In 66 diabetic eyes with no
      visual deterioration, the sensitivity and the specificity of SD-OCT without the
      use of mydriatics for the detection of fovea-threatening DME were determined. A
      definite diagnosis of DME was made under mydriasis, using slitlamp biomicroscopy
      with a contact lens. Eyes with fovea-threatening DME then underwent prophylactic
      focal/grid laser treatment. The main outcome measures were corrected VA and
      central macular thickness (CMT). RESULTS: A definitive diagnosis of DME was made
      in 5 of the 66 eyes, while macular thickening above the 99th percentile was
      detected in 11 (Cirrus(r)) or 13 (RS-3000(r)) eyes by SD-OCT. The focal/grid
      laser treatment of the 5 eyes with fovea-threatening DME successfully maintained
      good VA, which was 0.91 +/- 0.76 (average: 20/22; 0.04 +/- 0.12 logMAR) before
      treatment and 0.89 +/- 0.70 (average: 20/22; 0.05 +/- 0.15 logMAR; p = 0.88) 1
      year afterwards. The average CMT was stable before and after focal/grid lasering
      at 302 +/- 29 and 329 +/- 55 um, respectively (p = 0.99). CONCLUSIONS: The
      detection of fovea-threatening DME is feasible by SD-OCT without using
      mydriatics. Prophylactic treatment, such as with focal/grid lasers, was effective
      in maintaining good VA by avoiding an otherwise highly likely foveal involvement.
      (c) 2014 S. Karger AG, Basel.

PMID- 25059499
TI  - A statewide assessment of smoke-free policy in multiunit housing settings.
AB  - INTRODUCTION: The prevalence of smoke-free policies in multiunit housing (MUH) in
      South Dakota was examined. Owner beliefs about smoke-free policies were
      identified. METHODS: Stratified random sampling included 27 South Dakota counties
      classified as frontier, large rural, or urban. Data collection with MUH owners in
      selected counties employed a telephone survey with mailed backup. RESULTS: The
      owner response rate was 41.5% (324/780). A written smoke-free policy was reported
      by 175 (54.0%) owners, and 31 (10%) reported a verbal smoke-free policy. Owners
      in large rural counties (57.4%) had more written smoke-free policies than owners
      in urban (52.2%) and frontier (53.5%) counties. Only 8.5% of properties had
      policies covering both buildings and grounds. Owners without policies were more
      than twice as likely to manage U.S. Department of Housing and Urban Development
      subsidized units and were three times as likely to be current smokers. Owners
      without a smoke-free policy anticipated that a policy would decrease maintenance
      costs but increase turnover and vacancy rates. Nearly one-half (47.9%) of owners
      with no smoke-free policy had previously considered implementing a policy. Owners
      self-reported beliefs about smoke-free policies identified perceived benefits
      such as decreased maintenance and costs, improved tenant safety and health, and
      conscientious tenants. Perceived drawbacks included increased outdoor
      maintenance, enforcement problems, concerns about long-term tenants who smoke,
      and freedom/rights of smokers. CONCLUSIONS: This study provides a baseline
      assessment of smoke-free polices in MUH settings. Perceptions of owners without
      smoke-free policies focused on economic concerns that were inconsistent with
      reports from those owners with smoke-free policies.

PMID- 25059500
TI  - Desk-based workers' perspectives on using sit-stand workstations: a qualitative
      analysis of the Stand@Work study.
AB  - BACKGROUND: Prolonged sitting time has been identified as a health risk factor.
      Sit-stand workstations allow desk workers to alternate between sitting and
      standing throughout the working day, but not much is known about their
      acceptability and feasibility. Hence, the aim of this study was to qualitatively
      evaluate the acceptability, feasibility and perceptions of using sit-stand
      workstations in a group of desk-based office workers. METHODS: This article
      describes the qualitative evaluation of the randomized controlled cross-over
      Stand@Work pilot trial. Participants were adult employees recruited from a non
      government health agency in Sydney, Australia. The intervention involved using an
      Ergotron Workfit S sit-stand workstation for four weeks. After the four week
      intervention, participants shared their perceptions and experiences of using the
      sit-stand workstation in focus group interviews with 4-5 participants. Topics
      covered in the focus groups included patterns of workstation use, barriers and
      facilitators to standing while working, effects on work performance, physical
      impacts, and feasibility in the office. Focus group field notes and transcripts
      were analysed in an iterative process during and after the data collection period
      to identify the main concepts and themes. RESULTS: During nine 45-min focus
      groups, a total of 42 participants were interviewed. Participants were largely
      intrinsically motivated to try the sit-stand workstation, mostly because of
      curiosity to try something new, interest in potential health benefits, and the
      relevance to the participant's own and organisation's work. Most participants
      used the sit-stand workstation and three common usage patterns were identified:
      task-based routine, time-based routine, and no particular routine. Common
      barriers to sit-stand workstation use were working in an open plan office, and
      issues with sit-stand workstation design. Common facilitators of sit-stand
      workstation use were a supportive work environment conducive to standing,
      perceived physical health benefits, and perceived work benefits. When prompted,
      most participants indicated they were interested in using a sit-stand workstation
      in the future. CONCLUSIONS: The use of a sit-stand workstation in this group of
      desk-based office workers was generally perceived as acceptable and feasible.
      Future studies are needed to explore this in different desk-based work
      populations and settings.

PMID- 25059501
TI  - Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer
      cell lines.
AB  - In an effort to establish new candidates with enhanced anticancer activity of 5
      hydroxy-7-methyl-1,4-naphthoquinone scaffold (7-methyljuglone) previously
      isolated from the root extract of Euclea natalensis, a series of 7-methyljuglone
      derivatives have been synthesized and assessed for cytotoxicity on selected human
      cancer lines. These compounds were screened in vitro for anticancer activity on
      MCF-7, HeLa, SNO and DU145 human cancer cell lines by MTT assay. Most of them
      exhibited significant toxicity on cancer cell lines with lower IC50 values. The
      most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines
      with IC50 value of 5.3 and 6.8MUM followed by compound (5) with IC50 value of
      10.1 and 9.3MUM, respectively. Structure-activity relationship reveals that the
      fluoro substituents at position C-8 while hydroxyl substituents at C-2 and C-5
      positions played an important role in toxicity. 

PMID- 25059502
TI  - Cyclic acyl guanidines bearing carbamate moieties allow potent and dirigible
      cholinesterase inhibition of either acetyl- or butyrylcholinesterase.
AB  - A series of cyclic acyl guanidine with carbamate moieties have been synthesized
      and evaluated in vitro for their AChE and BChE inhibitory activities. Structure
      activity relationships identified compound 23 as a nanomolar and selective BChE
      inhibitor, while compound 32 exhibited nanomolar and selective AChE inhibition,
      selectivity depending on both the structure of the carbamate substituent as well
      as the position of guanidines-N substitution. The velocity of enzyme
      carbamoylation was analyzed and showed similar behavior to physostigmine.
      Phenolic compounds formed after carbamate transfer to the active site of
      cholinesterases showed additional neuroprotective properties on a hippocampal
      neuronal cell line (HT-22) after glutamate-induced intracellular reactive oxygen
      species generation. 

PMID- 25059503
TI  - Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and
      vascular disrupting agents.
AB  - Described herein is the development of a novel series of 7-anilino-indoline-N
      benzenesulfonamides, derived from ABT751 (1), as potent anticancer agents.
      Amongst the synthesized series, compounds 6, 12, 13, and 14 have shown comparable
      to better anticancer activity on comparing with compound 1. 7-(4
      Cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline (13) was found to be the
      most potent one with up to 6 fold better activity against KB, HT29, and MKN45
      cancer cell lines with IC50 values of 49.7, 149, and 92nM, respectively. Compound
      13 was also found inhibiting multidrug resistant cancer cell lines, blocking cell
      cycle at G2/M phase, and inhibiting tubulin polymerization. Capillary disruption
      assay results revealed that compound 13 was able to disrupt formed capillaries in
      a concentration-dependent manner without affecting cell viability. 

PMID- 25059504
TI  - Active immunisation of mice with GnRH lipopeptide vaccine candidates: Importance
      of T helper or multi-dimer GnRH epitope.
AB  - Active immunisation against gonadotropin releasing hormone (GnRH) is a potential
      alternative to surgical castration. This study focused on the development of a
      GnRH subunit lipopeptide vaccine. A library of vaccine candidates that contained
      one or more (up to eight) copies of monomeric or dimeric GnRH peptide antigen, an
      adjuvanting lipidic moiety based on lipoamino acids, and an additional T helper
      epitope, was synthesised by solid phase peptide synthesis. The candidates were
      evaluated in vivo in order to determine the minimal components of this vaccine
      necessary to induce a systemic immune response. BALB/c mice were immunised with
      GnRH lipopeptide conjugates, co-administered with or without Complete Freund's
      Adjuvant, followed by two additional immunisations. Significant GnRH-specific IgG
      titres were detected in sera obtained from mice immunised with four of the seven
      lipopeptides tested, with an increase in titres observed after successive
      immunisations. This study highlights the importance of for epitope optimisation
      and delivery system design when producing anti-hapten antibodies in vivo. The
      results of this study also contribute to the development of future clinical and
      veterinary immunocontraceptives. 

PMID- 25059505
TI  - Accelerated rehabilitation following Achilles tendon repair after acute rupture -
      Development of an evidence-based treatment protocol.
AB  - The acute rupture of the Achilles tendon is a protracted injury. Surgery is only
      the beginning of a long rehabilitation period. Therefore, the rehabilitation
      protocol is an integral aspect to restore the pre-injury activity level. Despite
      several trials available comparing different treatment regimes, there is still no
      consensus regarding the optimal protocol. Consequently, the aim of our study was
      to systematically search the evidence available and define a precise
      rehabilitation programme after operative repair of acute Achilles tendon rupture
      based on the trials with the highest level of evidence. We performed a systematic
      literature search in Medline, Embase and Cochrane library. We identified twelve
      randomized controlled trials comparing different treatment regimes after
      operative repair of the Achilles tendon. Five trials compared full to non weight
      bearing, all applying immobilization in equinus. Immediate full weight bearing
      led to significant higher patient satisfaction, earlier ambulation and return to
      pre-injury activity. Four trials compared early ankle mobilization to
      immobilization. All trials found mobilization to be superior as it shortens time
      to return to work and sports significantly. Three trials compared the combination
      of full weight bearing and early ankle mobilization to immobilization. This
      combination was most beneficial. Patients showed significantly higher
      satisfaction, less use of rehabilitation resources, earlier return to pre-injury
      activities and further demonstrated significantly increased calf muscle strength,
      reduced atrophy and tendon elongation. No study found an increased rerupture rate
      for the more progressive treatment. In conclusion, the rehabilitation protocol
      after Achilles tendon repair should allow immediate full weight bearing. After
      the second postoperative week controlled ankle mobilization by free plantar
      flexion and limited dorsiflexion at 0 degrees  should be applied. 

PMID- 25059506
TI  - Sudden survival improvement in critical neurotrauma: An exploratory analysis
      using a stratified statistical process control technique.
AB  - BACKGROUND: Outcome after trauma depends on patient characteristics, quality of
      care, and random events. The TRISS model predicts probability of survival (Ps)
      adjusted for Injury Severity Score (ISS), Revised Trauma Score (RTS), mechanism
      of injury, and age. Quality of care is often evaluated by calculating the number
      of "excess" survivors, year by year. In contrast, the Variable Life-Adjusted
      Display (VLAD) technique allows rapid detection of altered survival. VLAD adjusts
      each death or survival by the patient's risk status and graphically displays
      accumulated number of unexpected survivors over time. We evaluated outcome
      changes and their time relation to trauma service improvements. METHODS:
      Observational, retrospective study of the total 2001-2011 trauma population from
      a Level I trauma centre. Outcome was 30-day survival. Ps was calculated with the
      TRISS model, 2005 coefficients. VLAD graphs were created for the entire
      population and for subpopulations stratified by ISS level, ISS body region
      (Head/Neck, Face, Chest, Abdomen/Pelvic contents, Extremities/Pelvic girdle,
      External), and maximum Abbreviated Injury Scale (maxAIS) score in each region.
      Piecewise linear regression identified VLAD graph breakpoints. RESULTS: 12,191
      consecutive trauma patients (median age 35 years, 72% males, 91% blunt injury,
      41% ISS>=16) formed the dataset. Their VLAD graph indicated performance equal to
      TRISS predicted survival until a sudden improvement in late 2004. From then
      survival remained improved but unchanged through 2011. Total number of excess
      survivors was 141. Inspection of subgroup VLAD graphs showed that the increased
      survival mainly occurred in patients having at least one Head/Neck AIS 5 injury.
      The effect was present in both isolated and multitraumatised maxAIS 5 Head/Neck
      trauma. The remaining trauma population showed unchanged survival, superior to
      TRISS predicted, throughout the study period. Important general and neurotrauma
      targeted improvements in our trauma service could underlie our findings: A
      formalised trauma service, damage control resuscitation protocols, structured
      training, increased helicopter transfer capacity, consultant-based neurosurgical
      assessment, a doubling of emergency neurosurgical procedures, and improved
      neurointensive care. CONCLUSIONS: Stratified VLAD enables continuous, high
      resolution system analysis. We encourage trauma centres to explore their data and
      to monitor future system changes.

PMID- 25059508
TI  - [Adnexal skin tumors].

PMID- 25059507
TI  - Fibroblasts derived from long-lived insulin receptor substrate 1 null mice are
      not resistant to multiple forms of stress.
AB  - Reduced signalling through the insulin/insulin-like growth factor-1 signalling
      (IIS) pathway is a highly conserved lifespan determinant in model organisms. The
      precise mechanism underlying the effects of the IIS on lifespan and health is
      currently unclear, although cellular stress resistance may be important. We have
      previously demonstrated that mice globally lacking insulin receptor substrate 1
      (Irs1(-/-) ) are long-lived and enjoy a greater period of their life free from
      age-related pathology compared with wild-type (WT) controls. In this study, we
      show that primary dermal fibroblasts and primary myoblasts derived from Irs1(-/-)
      mice are no more resistant to a range of oxidant and nonoxidant chemical
      stressors than cells derived from WT mice. 

PMID- 25059509
TI  - Longer waits in emergency departments are inevitable as services reach capacity,
      report finds.

PMID- 25059510
TI  - Ion jelly conductive properties using dicyanamide-based ionic liquids.
AB  - The thermal behavior and transport properties of several ion jellys (IJs), a
      composite that results from the combination of gelatin with an ionic liquid (IL),
      were investigated by dielectric relaxation spectroscopy (DRS), differential
      scanning calorimetry (DSC), and pulsed field gradient nuclear magnetic resonance
      spectroscopy (PFG NMR). Four different ILs containing the dicyanamide anion were
      used: 1-butyl-3-methylimidazolium dicyanamide (BMIMDCA), 1-ethyl-3
      methylimidazolium dicyanamide (EMIMDCA), 1-butyl-1-methylpyrrolidinium
      dicyanamide (BMPyrDCA), and 1-butylpyridinium dicyanamide (BPyDCA); the bulk ILs
      were also investigated for comparison. A glass transition was detected by DSC for
      all materials, ILs and IJs, allowing them to be classified as glass formers.
      Additionally, an increase in the glass transition temperature upon dehydration
      was observed with a greater extent for IJs, attributed to a greater hindrance
      imposed by the gelatin matrix after water removal, rendering the IL less mobile.
      While crystallization is observed for some ILs with negligible water content, it
      was never detected for any IJ upon thermal cycling, which persist always as fully
      amorphous materials. From DRS measurements, conductivity and diffusion
      coefficients for both cations (D+) and anions (D-) were extracted. D+ values
      obtained by DRS reveal excellent agreement with those obtained from PFG NMR
      direct measurements, obeying the same VFTH equation over a large temperature
      range (DeltaT ~ 150 K) within which D+ varies around 10 decades. At temperatures
      close to room temperature, the IJs exhibit D values comparable to the most
      hydrated (9%) ILs. The IJ derived from EMIMDCA possesses the highest conductivity
      and diffusion coefficient, respectively, ~10(-2) S.cm(-1) and ~10(-10) m(2).s(
      1). For BMPyrDCA the relaxational behavior was analyzed through the complex
      permittivity and modulus formalism allowing the assignment of the detected
      secondary relaxation to a Johari-Goldstein process. Besides the relevant
      information on the more fundamental nature providing physicochemical details on
      ILs behavior, new doorways are opened for practical applications by using IJ as a
      strategy to produce novel and stable electrolytes for different electrochemical
      devices. 

PMID- 25059511
TI  - First-line managers' descriptions and reflections regarding their staff's access
      to empowering structures.
AB  - AIM: To elucidate first-line managers' descriptions and reflections regarding
      their staff's access to empowering structures using Kanter's theory of structural
      empowerment. BACKGROUND: Good structural conditions within workplaces are
      essential to employees' wellbeing, and their ability to access empowerment
      structures is largely dependent on the management. METHOD: Twenty-eight first
      line managers in elderly care were interviewed. Deductive qualitative content
      analysis was used to analyse data. RESULTS: Managers perceived that staff had
      varying degrees of access to the empowering structures described in Kanter's
      theory - and that they possessed formal power in their roles as contact persons
      and representatives. The descriptions mostly started from the managers' own
      actions, although some started from the needs of staff members. CONCLUSION: All
      managers described their staff's access to the empowering structures in Kanter's
      theory as important, yet it seemed as though this was not always reflected on and
      discussed as a strategic issue. IMPLICATIONS FOR NURSING MANAGEMENT: Managers
      could make use of performance and appraisal dialogues to keep up to date on
      staff's access to empowering structures. Recurrent discussions in the management
      group based on such current information could promote staff's access to power
      through empowering structures and make job definitions a strategic issue in the
      organisation.

PMID- 25059512
TI  - Excitatory amino acid transporter 2 downregulation correlates with thalamic
      neuronal death following kainic acid-induced status epilepticus in rat.
AB  - Recurrent seizures without interictal resumption (status epilepticus) have been
      reported to induce neuronal death in the midline thalamic region that has
      functional roles in memory and decision-making; however, the pathogenesis
      underlying status epilepticus-induced thalamic neuronal death is yet to be
      determined. We performed histological and immunohistochemical studies as well as
      cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging
      spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7
      weeks after birth, body weight 250-300 g) treated with intraperitoneal injection
      of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline
      solution (n = 20). Histological study using paraffin-embedded specimens revealed
      neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with
      calcium deposition in the midline thalamic region of epileptic rats. The
      distribution of neuronal death was associated with focal loss of immunoreactivity
      for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for
      glutamate and increase in number of Iba-1-positive microglial cells showing
      swollen cytoplasm and long processes. Double immunofluorescence study
      demonstrated co-expression of interleukin-1 beta (IL-1beta) and inducible nitric
      oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity
      in reactive astrocytes. These microglial alterations and astrocytic EAAT2
      downregulation were also observed in tissue without obvious neuronal death in
      kainic acid-treated rats. These results suggest the possible role of glutamate
      excitotoxicity in neuronal death in the midline thalamic region following kainic
      acid-induced status epilepticus due to astrocytic EAAT2 downregulation following
      microglial activation showing upregulation of IL-1beta and iNOS.

PMID- 25059513
TI  - Analyzing the impact of the European unitary patent system on worldwide
      biotechnology.
AB  - Following the deepest recession in generations, the European Union (EU) has
      proposed a plan to rebuild its economy that includes restructuring of its science
      and innovation system. In this context, the EU has rolled out a unitary patent
      system to improve technological development across European countries. This
      decision brings to light a new scientific and administrative scenario that will
      change the rules of innovation in Europe, with consequences for global
      biotechnology. 

PMID- 25059514
TI  - Kinematics and spatiotemporal parameters of infant-carrying in olive baboons.
AB  - In the field of biomechanics of quadrupedal locomotion in primates, infant
      carrying has received little attention. This study presents the first
      biomechanical study of infant-carrying in captive female olive baboons (Papio
      anubis). We test whether females carrying infants conform 1) to the Support
      Polygon Model (Rollinson and Martin: Symp Zool Soc Lond 48 (1981) 377-427) of
      gait selection, according to which diagonality should decrease when the infant is
      carried cranially and increase when the infant is carried dorsally and caudally;
      2) to Biewener's (Biewener: Science 245 () 45-48) theory of limb postures,
      according to which females should extend their hind limbs more due to infant
      load, especially in the later stages when the infant is not fully autonomous but
      relatively heavy. This study focuses on the sagittal kinematics of quadrupedal
      gaits (joint angles and spatiotemporal parameters) of four females with and
      without infant loads at the CNRS Primatology Station (France). High-speed video
      recordings were made using the technical platform "Motion Analysis of Primates"
      available in the animals' place of life. Regarding diagonality, our results do
      not fully conform to those predicted by the Support Polygon Model of gait
      selection; however, the model cannot be rejected at this stage in experiment.
      With regard to limb posture, our results do not support Biewener's (Biewener:
      Science 245 () 45-48) theory: loaded females do not extend their hind limbs more
      as predicted; on the contrary, the hind limbs tend to be more flexed when the
      infant they carry is relatively heavy.

PMID- 25059515
TI  - [Stratification of clinical risk groups in a population over 65 years: features
      and nursing assessment].
AB  - OBJECTIVE: To analyze the characteristics of the population over 65 years served
      in a Basic Health Area, according to the Clinical Risk Group (CRG) classification
      and geriatric assessment test performed by the nurse in relation to their
      complexity. METHODS: A descriptive, cross-sectional and observational prevalence
      study was conducted on the population over 65 years served in a Basic Health
      Area. The variables collected were: socio-demographic, CRG classification,
      diseases (ICD-10), healthcare activity, geriatric assessment, and preventive
      activities. The CRG classification was used as a measurement tool. Data was
      collected from the Primary Care computerized clinical history (e-CAP). RESULTS:
      Population over 65 years: 3,219 people; served at home, 130 (4%), and in
      residential institutions, 92 (2.85%). The population was grouped into: CRG 1-2:
      83 (2.5%); CRG 3: 62 (2%); CRG 4: 99 (3%); CRG 5: 537 (17%); CRG 6: 2,077
      (64.5%); CRG 7: 276 (8.6%); CRG 8: 61 (2%); CRG 9: 14 (0.4%). Most frequent
      chronic diseases: 69.12% AHT; 24.94% DM; 19.51% depression; 11.09% kidney
      failure. The groups 6-7-8 that were analyzed included 2,414 people (75%). Of
      those within CRG 6-7-8, only 570 (24%) had tests carried out by the geriatric
      nurse. The mean number of individuals assigned by a nurse for CRG 6-7-8 was 302.
      CONCLUSIONS: The introduction of classification systems in clinical practice,
      such as the CRG, along with the use of the new information and communication
      technologies, helps to incorporate predictive models of health needs. It also
      promotes proactive actions by nurses and the team to prevent complications of
      diseases, as well as improving efficiency in the use of services and in care of
      the complex patients.

PMID- 25059516
TI  - [Motivation to change unhealthy life styles and cardiovascular risk].
AB  - OBJECTIVE: Study the relationship between motivation to change unhealthy life
      styles and cardiovascular risk. METHOD: Cross sectional study, random, stratified
      by age, carried out in the field of primary care with a sample of 369 people. It
      was felt that with smoking or smoking cessation active consumption less than a
      year, the physical habit was valued at work and leisure, food habits were
      assessed in adherence to mediterranean diet and the stages of motivation were
      categorized precontemplative phase to maintenance phase. The cardiovascular risk
      was stratified with the SCORE table calibrated in Spain. RESULTS: The 49.6% were
      men and 50.4% were women, with an average age of 41.2 years. The prevalence of
      smoking was 31.4% (95% CI 26.56-36,30), 58% in sedentary lifestyle (95% CI 52.27
      62,63) and 68% for bad diet (95% CI 63.97-73,69). The 69.8% of smokers, 77.8% of
      sedentary and 48.4% of people without proper diet was precontemplative to change
      their lifestyles. CONCLUSIONS: Precontemplative stages in unhealthy life styles
      have association with risk factors and increase the global cardiovascular risk.
      The transtheoretical model is a useful tool for the assessment of unhealthy
      behaviors in lifestyles.

PMID- 25059517
TI  - A model of hunter-gatherer skeletal element transport: the effect of prey body
      size, carriers, and distance.
AB  - Zooarchaeologists frequently use the relative abundance of skeletal elements in
      faunal assemblages in conjunction with foraging theory models to infer
      subsistence decisions made by prehistoric hunter-gatherers. However, foraging
      models applied to ethnoarchaeological cases have had variable success linking
      skeletal transport decisions with foraging predictions. Here, we approach this
      issue with the well-known Hadza data to statistically model the skeletal element
      transport decisions in response to distance from the residential hub and the
      number of carriers available for carcass transport. We compare our modeling
      approach to the traditional skeletal element utility curves from Binford's work
      with the Nunamiut, and to the more recently proposed Shannon evenness measure.
      Our approach, based on standard yet powerful statistical modeling techniques, can
      help researchers gain increased insight into the prey part transport responses of
      hunter-gatherers. Our analyses treat individual prey skeletal elements by body
      size as the response variable. The results of this analysis suggest that utility
      curves, and the Shannon evenness approach as a proxy for utility curves, are
      problematic for making statements about prehistoric foraging from
      zooarchaeological data. Transport distance does not explain a significant portion
      of small prey (size class 2) skeletal element transport variation. However,
      distance explains a great deal of transport variation in large prey (size classes
      4 and 5). Inferences from skeletal element profiles should be made relative to
      prey body size and the discard probability of individual elements. Understanding
      the influence of these variables allows construction of a framework for testing
      archaeological element profiles against ethnographically derived transport
      models. 

PMID- 25059518
TI  - Anteriorly pedicled wide temporalis muscle flap with the minimum zygomatic
      osteotomy technique for post-discectomy temporomandibular joint arthroplasty.
AB  - An anteriorly pedicled temporalis muscle flap has been shown to be a suitable
      interpositional material for the treatment of ankylosis and post-discectomy
      arthroplasty. The passage of the wide flap beneath the zygomatic arch into the
      joint space can be difficult owing to its bulk, causing excessive trauma to the
      vascularized pedicle. We describe the use of minimum zygomatic osteotomy without
      fixation for the passage of an anteriorly pedicled wide temporalis muscle flap
      for post-discectomy arthroplasty. 

PMID- 25059519
TI  - "Companion diagnostics": has their time come and gone?
AB  - Rapid development of molecularly targeted drugs requires a "companion diagnostic"
      that could delay drug development and limit availability of active drugs for
      relevant patients. Were the negative results from MetMab studies in patients with
      advanced non-small cell lung cancer due to drug failure or failure of the right
      companion diagnostic?

PMID- 25059521
TI  - Distal biceps brachii tendon repair complicated by a suture granuloma mimicking a
      soft-tissue sarcoma: a case report and review of the literature.

PMID- 25059520
TI  - Differential responses of osteoblasts and macrophages upon Staphylococcus aureus
      infection.
AB  - BACKGROUND: Staphylococcus aureus (S. aureus) is one of the primary causes of
      bone infections which are often chronic and difficult to eradicate. Bacteria like
      S. aureus may survive upon internalization in cells and may be responsible for
      chronic and recurrent infections. In this study, we compared the responses of a
      phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon
      S. aureus internalization. RESULTS: We found that upon internalization, S. aureus
      could survive for up to 5 and 7 days within macrophages and osteoblasts,
      respectively. Significantly more S. aureus was internalized in macrophages
      compared to osteoblasts and a significantly higher (100 fold) level of live
      intracellular S. aureus was detected in macrophages compared to osteoblasts.
      However, the percentage of S. aureus survival after infection was significantly
      lower in macrophages compared to osteoblasts at post-infection days 1-6.
      Interestingly, macrophages had relatively lower viability in shorter infection
      time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer
      infection time periods (i.e. 6-8 h; significant at 8 h) compared to osteoblasts.
      In addition, S. aureus infection led to significant changes in reactive oxygen
      species production in both macrophages and osteoblasts. Moreover, infected
      osteoblasts had significantly lower alkaline phosphatase activity at post
      infection day 7 and infected macrophages had higher phagocytosis activity
      compared to non-infected cells. CONCLUSIONS: S. aureus was found to internalize
      and survive within osteoblasts and macrophages and led to differential responses
      between osteoblasts and macrophages. These findings may assist in evaluation of
      the pathogenesis of chronic and recurrent infections which may be related to the
      intracellular persistence of bacteria within host cells.

PMID- 25059522
TI  - Delivering TB/HIV services in Ghana: a comparative study of service delivery
      models.
AB  - BACKGROUND: TB and HIV interaction increases TB incidence and HIV adverse
      outcomes. Integration improves patients' access to comprehensive care. This paper
      compares the impact of increasing integration on TB/HIV service delivery.
      METHODS: Three hospitals with different delivery models were identified and a
      survey of TB cases registered between June 2007 and December 2008 conducted. HIV
      screening, co-trimoxazole preventive therapy (CPT) and antiretroviral therapy
      (ART) uptake for HIV-positive TB patients were compared. RESULTS: Of the 590 TB
      patients, 85.9% (507/590) knew their HIV status. HIV screening was highest (98.6%
      [95%CI: 97.6-99.5%]) at the one-stop shop (OSS) and lowest (72.5% [71.9-73.9%])
      at the referral site (RS). CPT was highest [(93.8% [91.0-96.7%]) at the RS and
      least (74.7% [72.8-76.5%]) at the partially-integrated site (PIS). At the OSS it
      was 82.3% (80.6-84.0%). ART was highest (59.5% [58.0-61.0%]) at the PIS, and
      10.8% (10.4-11.1%) at the RS. No ART records existed at the OSS. CONCLUSIONS:
      Increasing integration improved HIV screening but not CPT or ART uptake. There
      was insufficient evidence to identify the most effective model due to design
      limitations and health system barriers. More research and training is needed to
      improve uptake, data completeness and accuracy.

PMID- 25059523
TI  - Mass drug administration with praziquantel reduces the prevalence of Schistosoma
      mansoni and improves liver morbidity in untreated preschool children.
AB  - BACKGROUND: The aim of this study was to investigate the effects of mass drug
      administration on Schistosoma mansoni prevalence and associated liver morbidity
      in treated school-aged children and untreated preschool children. METHODS: In
      April 2008, parasitological (using the Kato-Katz method) and morbidity
      (determined by portal vein score) data were collected from 263 schoolchildren
      aged 6 and 7 years. The children had never received praziquantel. In March 2010,
      following two annual rounds of mass drug administration, 207 children aged 8 and
      9 years old were examined to determine the effect of treatment. In addition, 158
      untreated 6-year-olds were assessed to compare with the untreated children from
      2008. RESULTS: Treatment significantly decreased the prevalence of S. mansoni and
      associated morbidity in the treated groups. The untreated preschool children also
      showed a significant decrease in the prevalence of S. mansoni, from 21.1% (2008)
      to 6.3% (2010) (p<0.001). The percentage of untreated schoolchildren with a
      normal portal vein score increased significantly from 57.8% (2008) to 70.3%
      (2010) (p=0.029). CONCLUSION: The significantly lower rates of S. mansoni and the
      decreased liver morbidity in untreated preschool children in 2010 suggest
      decreased environmental transmission rates and improved liver morbidity in
      untreated children following several rounds of mass drug administration.

PMID- 25059524
TI  - Non-clinical factors associated with TB: important for DOTS impact evaluation and
      disease elimination.
AB  - Initial optimism that DOTS (Directly Observed Treatment, Short-course) would have
      a dramatic effect on TB incidence rates in developing countries has not been
      supported by the evidence accumulated so far. Indeed, where TB incidence rates
      have decreased, non-clinical socio-economic factors appear to have played at
      least as great a role. We postulate that in those settings with little or no
      decrease in TB incidence, there are likely to be common pathway blockages that
      interfere with the effectiveness of DOTS implementation as socio-economic factors
      evolve. Measuring socio-economic trends, as well as DOTS implementation, is
      important for understanding TB control and opens up the opportunity for broader
      public health engagement. 

PMID- 25059525
TI  - How 'The association of endemic elephantiasis of the lower legs in East Africa
      with soil derived from volcanic rocks' has underpinned progress in podoconiosis
      research.
AB  - We demonstrate how an article from the Transactions of the Royal Society of
      Tropical Medicine & Hygiene archive has triggered two important series of studies
      into the aetiology and distribution of podoconiosis, 30 years after first
      publication of the article. It indicates the value of becoming familiar with
      hypotheses raised by earlier investigators and of direct use of historical data
      in understanding trends in disease distribution. 

PMID- 25059526
TI  - The current crisis in human resources for health in Africa: the time to adjust
      our focus is now.
AB  - The challenges as we strive towards universal health coverage are many, but the
      need for an improved health workforce is chief among them. Unfortunately the
      global deficit in skilled professionals continues to increase. Nevertheless,
      there are potential solutions, and success stories are well documented when the
      approach is on system building and sustainability. As we approach 2015 and the
      Millennium Development Goals, we must shift our focus to a more distant time
      point in order to achieve the dramatic gains in global health that are possible.
      However, we must understand that there can be no health without a workforce. 

PMID- 25059527
TI  - Transmission of helminth eggs through hands in a high-risk community.
AB  - BACKGROUND: The role that hands play in the transmission of Ascaris is not well
      understood. METHODS: A newly developed method to quantify the presence helminth
      eggs on hands was tested among a group of farmers in Vietnam. High turbidity in
      hand rinse samples meant that the adopted sugar solution had to be replaced by
      zinc sulphate as a flotation solution. RESULTS: The survey found 34% (31/90) of
      study participant hands' were positive for helminth eggs, though concentrations
      were low and ranged from 0-10 eggs/2 hands. The use of fresh excreta in
      agriculture was the only variable that showed an association with the
      concentrations of eggs found on hands. CONCLUSIONS: The results highlight the
      need to promote handwashing with soap to prevent the transmission of soil
      transmitted helminth infections.

PMID- 25059528
TI  - BactImAS: a platform for processing and analysis of bacterial time-lapse
      microscopy movies.
AB  - BACKGROUND: The software available to date for analyzing image sequences from
      time-lapse microscopy works only for certain bacteria and under limited
      conditions. These programs, mostly MATLAB-based, fail for microbes with irregular
      shape, indistinct cell division sites, or that grow in closely packed
      microcolonies. Unfortunately, many organisms of interest have these
      characteristics, and analyzing their image sequences has been limited to time
      consuming manual processing. RESULTS: Here we describe BactImAS - a modular,
      multi-platform, open-source, Java-based software delivered both as a standalone
      program and as a plugin for Icy. The software is designed for extracting and
      visualizing quantitative data from bacterial time-lapse movies. BactImAS uses a
      semi-automated approach where the user defines initial cells, identifies cell
      division events, and, if necessary, manually corrects cell segmentation with the
      help of user-friendly GUI and incorporated ImageJ application. The program
      segments and tracks cells using a newly-developed algorithm designed for movies
      with difficult-to-segment cells that exhibit small frame-to-frame differences.
      Measurements are extracted from images in a configurable, automated fashion and
      an SQLite database is used to store, retrieve, and exchange all acquired data.
      Finally, the BactImAS can generate configurable lineage tree visualizations and
      export data as CSV files. We tested BactImAS on time-lapse movies of
      Mycobacterium smegmatis and achieved at least 10-fold reduction of processing
      time compared to manual analysis. We illustrate the power of the visualization
      tool by showing heterogeneity of both icl expression and cell growth atop of a
      lineage tree. CONCLUSIONS: The presented software simplifies quantitative
      analysis of time-lapse movies overall and is currently the only available
      software for the analysis of mycobacteria-like cells. It will be of interest to
      the community of both end-users and developers of time-lapse microscopy software.

PMID- 25059529
TI  - Inflammatory myofibroblastic tumours of the urinary bladder: multi-centre 18-year
      experience.
AB  - OBJECTIVE: To review a series of inflammatory myofibroblastic tumours (IMTs) of
      the urinary bladder in 10 hospitals in Hong Kong. METHODS: A database search in
      the pathology archives of 10 hospitals in Hong Kong from 1995 to 2013 was
      performed using the key words 'inflammatory myofibroblastic tumour',
      'inflammatory pseudotumour' and 'spindle cell lesion'. Patient characteristics,
      clinical features, histological features, immunohistochemical staining results
      and treatment outcomes were reviewed. RESULTS: Nine cases of IMT of the urinary
      bladder were retrieved. The mean age was 45.4 +/- 22.8 years (range 11-78). Eight
      patients (88.9%) presented with haematuria and 5 patients (55.6%) had anaemia
      with a mean haemoglobin level of 6.8 +/- 1.3 g/dl. Histologically, the majority
      of patients (77.8%) had a compact spindle cell pattern. Anaplastic lymphoma
      kinase staining was positive in 75% of cases. During a mean follow-up period of
      43.4 months (range 8-94), none of them developed any local recurrence or distant
      metastasis. CONCLUSIONS: A high index of suspicion of IMT should be maintained
      for young patients presenting with bleeding bladder tumours and significant
      anaemia. IMTs of the urinary bladder run a benign disease course, and good
      prognosis can be achieved after surgical resection.

PMID- 25059530
TI  - An analysis of the Research Team-Service User relationship from the Service User
      perspective: a consideration of 'The Three Rs' (Roles, Relations, and
      Responsibilities) for healthcare research organisations.
AB  - BACKGROUND: This article debates interview data from service users who engaged
      with the work of a Collaboration for Leadership in Applied Health Research and
      Care (CLAHRC). The evidence base, to date, concerning the nature of CLAHRC work
      at the frontline (i.e. What is it actually like to do CLAHRC work?) is meagre;
      thus, this article represents an original contribution to that literature.
      Further, this article analyses service users' participation in research - as
      members of the research team - and so contributes to the body of developing
      literature regarding involvement too. OBJECTIVE: This article explores the nature
      of the Research Team-Service User relationship, plus associated roles, relations
      and responsibilities of collaborative health research. DESIGN: Qualitative social
      science research was undertaken in a health-care research organization utilizing
      interview method and a medical sociology and organizational sociology theoretical
      framework for analysis. Data utilized originate from a larger evaluation study
      that focuses on the CLAHRC as an iterative organization and explores members'
      experiences. RESULTS: There can be a disparity between initial expectations and
      actual experiences of involvement for service users. Therefore, as structured via
      'The Three Rs' (Roles, Relations and Responsibilities), aspects of the
      relationship are evaluated (e.g. motivation, altruism, satisfaction,
      transparency, scope, feedback, communication, time). Regarding the inclusion of
      service users in health research teams, a careful consideration of 'The Three Rs'
      is required to ensure expectations match experiences.

PMID- 25059531
TI  - Functional characterization and phylogenetic analysis of acquired and intrinsic
      macrolide phosphotransferases in the Bacillus cereus group.
AB  - The Bacillus cereus group is composed of Gram-positive spore-forming bacteria of
      clinical and ecological importance. More than 200 B. cereus group isolates have
      been sequenced. However, there are few reports of B. cereus group antibiotic
      resistance genes. This study identified two functional classes of macrolide
      phosphotransferases (Mphs) in the B. cereus group. Cluster A Mphs inactivate 14-
      and 15-membered macrolides while Cluster B Mphs inactivate 14-, 15- and 16
      membered compounds. The genomic region surrounding the Cluster B Mph gene is
      related to various plasmid sequences, suggesting that this gene is an acquired
      resistance gene. In contrast, the Cluster A Mph gene is located in a chromosomal
      region conserved among all B. cereus group isolates, and data indicated that it
      was acquired early in the evolution of the group. Therefore, the Cluster A gene
      can be considered an intrinsic resistance gene. However, the gene itself is not
      present in all strains and our comparative genomics analyses showed that it is
      exchanged among strains of the B. cereus group by the mean of homologous
      recombination. These results provide an alternative mechanism to intrinsic
      resistance.

PMID- 25059532
TI  - Guanfacine modulates the emotional biasing of amygdala-prefrontal connectivity
      for cognitive control.
AB  - Functional interactions between amygdala and prefrontal cortex provide a cortical
      entry point for emotional cues to bias cognitive control. Stimulation of alpha2
      adrenoceptors enhances the prefrontal control functions and blocks the amygdala
      dependent encoding of emotional cues. However, the impact of this stimulation on
      amygdala-prefrontal interactions and the emotional biasing of cognitive control
      have not been established. We tested the effect of the alpha2 adrenoceptor
      agonist guanfacine on psychophysiological interactions of amygdala with
      prefrontal cortex for the emotional biasing of response execution and inhibition.
      Fifteen healthy adults were scanned twice with event-related functional magnetic
      resonance imaging while performing an emotional go/no-go task following
      administration of oral guanfacine (1mg) and placebo in a double-blind,
      counterbalanced design. Happy, sad, and neutral faces served as trial cues.
      Guanfacine moderated the effect of face emotion on the task-related functional
      connectivity of left and right amygdala with left inferior frontal gyrus compared
      to placebo, by selectively reversing the functional co-activation of the two
      regions for response execution cued by sad faces. This shift from positively to
      negatively correlated activation for guanfacine was associated with selective
      improvements in the relatively low accuracy of responses to sad faces seen for
      placebo. These results demonstrate the importance of functional interactions
      between amygdala and inferior frontal gyrus to both bottom-up biasing of
      cognitive control and top-down control of emotional processing, as well as for
      the alpha2 adrenoceptor-mediated modulation of these processes. These mechanisms
      offer a possibile method to address the emotional reactivity that is common to
      several psychiatric disorders. 

PMID- 25059534
TI  - Lone aortic insufficiency and conduction disease: a marker of reactive arthritis.
AB  - A 48-year-old male with history of chronic arthritis and uveitis presented with 1
      year of progressively reduced exercise capacity and nonexertional chest pain.
      Physical examination was consistent with severe aortic insufficiency. An
      electrocardiogram demonstrated sinus rhythm with first degree atrioventricular
      block. Transthoracic and transesophageal echocardiography demonstrated severe
      lone central aortic insufficiency of a trileaflet valve due to leaflet
      thickening, retraction of leaflet margins and mild aortic root dilation in the
      setting of left ventricular dilatation. In addition, computed tomographic
      angiography revealed a small focal aneurysm of the distal transverse arch. He was
      found to be positive for the immunogenetic marker HLA-B27. The patient
      subsequently underwent uncomplicated mechanical aortic valve replacement. The
      diagnosis of HLA-B27 associated cardiac disease should be entertained in any
      individual with lone aortic insufficiency, especially if accompanied by
      conduction disease. 

PMID- 25059533
TI  - Development and validation of a disease-targeted quality of life instrument for
      chronic diverticular disease: the DV-QOL.
AB  - BACKGROUND: Colonic diverticular disease is typically conceived as acute
      diverticulitis attacks surrounded by periods of clinical silence. However,
      evolving data indicate that many patients have persistent symptoms and diminished
      health-related quality of life (HRQOL) long after acute attacks. We developed a
      disease-targeted HRQOL measure for symptomatic uncomplicated diverticular disease
      (SUDD)-the diverticulitis quality of life (DV-QOL) instrument. METHODS: We
      conducted a systematic literature review to craft a conceptual model of SUDD
      HRQOL. This was complemented by three focus groups including 45 SUDD patients. We
      developed items based on our literature search, focus groups, and cognitive
      debriefings. We administered the items to SUDD patients with persistent symptoms
      following a confirmed diverticulitis event. We created scales based on factor
      analysis and evaluated the scales for reliability and validity. RESULTS: Concept
      elicitation revealed a range of illness experiences attributed to SUDD. Coding of
      20,490 transcribed words yielded a 52-code network with four primary, condition
      related concepts: (1) physical symptoms (e.g., bloating); (2) behaviors (e.g.,
      restrictions); (3) cognitions and concerns (e.g., fear); and (4) impact and
      consequences (e.g., absenteeism, anxiety). Based on patient language, we
      developed the 17-item DV-QOL instrument. In a cross-sectional validation sample
      of 197 patients, DV-QOL discriminated between patients with recent versus distant
      diverticulitis events and correlated highly with Short Form 36 and hospital
      anxiety and depression scores. CONCLUSIONS: Patients with SUDD attribute a wide
      range of negative psychological, social, and physical symptoms to their
      condition, both during and after acute attacks; DV-QOL captures these symptoms in
      a valid, reliable manner.

PMID- 25059535
TI  - Negative outcomes after liver transplantation in patients with alcoholic liver
      disease beyond the fifth post-transplant year.
AB  - Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol
      consumption after liver transplantation (LT), numerous studies indicate that long
      term results are not compromised. This study focused on evaluating the impact of
      ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary
      LT recipients included in this study, 97 underwent transplantation for ALD.
      Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the
      only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was
      similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655)
      but worse during the five subsequent years among the five-yr survivors (70.6% vs.
      92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond
      the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717).
      Conversely, alcohol relapse increased the risk of death only during the first
      five post-transplant years (p = 0.039). There were no significant differences
      regarding graft failure incidence between ALD and non-ALD recipients up to the
      fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs.
      5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative
      effects on post-transplant outcomes beyond the fifth post-transplant year, not
      attributable to recidivism. 

PMID- 25059536
TI  - Violence prevention education program for psychiatric outpatient departments.
AB  - OBJECTIVE: Approximately 40 % of psychiatrists and up to 64 % of psychiatric
      residents have been physically assaulted. Ranges of 72-96 % of psychiatric
      residents in various studies have been verbally threatened. As violence risk
      occurs in outpatient settings, our department developed a quality and safety
      curriculum designed to prepare psychiatric residents and staff to optimally
      respond to aggressive outpatients and violence threats or events. METHODS: In
      2011 and 2012, we offered an 8-part violence prevention performance improvement
      curriculum/program including (1) situational awareness/creating a safe
      environment; (2) violence de-escalation training; (3) violence risk assessment
      training, use of risk assessment tools, and medical record documentation; (4)
      violence safety discharge planning; (5) legal issues and violence; (6) "shots
      fired on campus" video/discussion; (7) "2011 violence threat simulation"
      video/discussion; and (8) violence threat simulation exercise. This program was
      offered to approximately 60 psychiatric residents/staff in each year. RESULTS: We
      obtained qualitative comments about the entire program and data from 2 years of
      post-event surveys on the usefulness of the "violence threat simulation
      exercise." The large majority of comments about program elements 1 to 7 were
      positive. In 2011 and 2012, respectively, 76 and 86 % of participants responded
      to a post-event survey of the violence threat simulation exercise; 90 and 88 % of
      participants, respectively, reported the simulation to be very helpful/somewhat
      helpful; and 86 and 82 % of participants, respectively, reported feeling much
      better/better prepared to deal with a violent event. Although some participants
      experienced anxiety, sleep disturbances, increase in work safety concerns, and/or
      traumatic memories, the majority reported no post-simulation symptoms (72 and 80
      %, respectively). CONCLUSIONS: Although we are unable to demonstrate that this
      program effectively prevents violence, the overall positive response from
      participants encourages us to continue developing our quality and safety program
      and to offer our easily reproducible and modifiable curriculum to others.

PMID- 25059537
TI  - Training for suicide risk assessment and suicide risk formulation.
AB  - Suicide and suicidal behaviors are highly associated with psychiatric disorders.
      Psychiatrists have significant opportunities to identify at-risk individuals and
      offer treatment to reduce that risk. Although a suicide risk assessment (SRA) is
      a core competency requirement, many lack the requisite training and skills to
      appropriately assess for suicide risk. Moreover, the standard of care requires
      psychiatrists to foresee the possibility that a patient might engage in suicidal
      behavior, hence to conduct a suicide risk formulation (SRF) sufficient to guide
      triage and treatment planning. An SRA gathers data about observable and reported
      symptoms, behaviors, and historical factors that are associated with suicide risk
      and protection, ascertained by way of psychiatric interview; collateral
      information from family, friends, and medical records; and psychometric scales
      and/or screening tools. Based on data collected via an SRA, an SRF is a process
      whereby the psychiatrist forms a judgment about a patient's foreseeable risk of
      suicidal behavior in order to inform triage decisions, safety and treatment
      plans, and interventions to reduce risk. This paper addresses the need for a
      revised training model in SRA and SRF, and proposes a model of training that
      incorporates the acquisition of skills, relying heavily on case application
      exercises. 

PMID- 25059538
TI  - Haemoglobinopathies in eastern Indian states: a demographic evaluation.
AB  - Haemoglobinopathies are a leading cause of child mortality worldwide, although
      with a variable geographical incidence. A reliable estimate of prevalence of the
      disease is necessary for reducing its burden. However, most studies in India are
      either hospital based or from certain regions of the country and hence may not
      realistically reflect the disease burden. The eastern Indian states of Bihar,
      Chhattisgarh and Jharkhand and eastern region of Uttar Pradesh, which comprise
      ~25 % population of the country, are poorly studied with respect to
      haemoglobinopathies. The present study, conducted on 1,642 individuals from this
      region, shows a frequency of 3.4 % for beta-thalassaemia trait (BTT), 3.4 % for
      sickle cell haemoglobin trait (HbS)/haemoglobin E trait (HbE) and 18 % for alpha
      globin defects. While BTT mutations are distributed rather uniformly across the
      region, HbS occurs only in Chhattisgarh and Jharkhand, the regions rich in tribal
      populations. The frequency of alpha-gene mutation is strikingly high, occurring
      even in individuals with normal blood count, in tribal as well as non-tribal
      groups. The mutation spectrum of BTT is also distinct since the common mutations,
      IVS1-1 (G-T) and 619 bp del, are absent while CD15 (G-A) is the second most
      frequent. The HbA2 level in the suspected cases is strikingly low. We demonstrate
      association of the low HbA2 level with vitamin B12 and folate deficiency in this
      cohort. Thus, the present report besides providing an estimate of the carrier
      frequency of beta-thalassaemia traits also confirms high prevalence of alpha-gene
      defects and regional heterogeneity in distribution of HbS in the eastern parts of
      India. 

PMID- 25059539
TI  - In vivo and in vitro attenuation of naloxone-precipitated experimental opioid
      withdrawal syndrome by insulin and selective KATP channel modulator.
AB  - RATIONALE: Opiate exposure for longer duration develops state of dependence in
      humans and animals, which is revealed by signs and symptoms of withdrawal
      precipitated by opioid receptor antagonists. The sudden withdrawal of opioids
      produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP
      sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown
      to modulate morphine withdrawal. OBJECTIVE: Present study has been structured to
      investigate the role of insulin and pharmacological modulator of KATP channel
      (gliclazide) in experimental morphine withdrawal syndrome, both invivo and
      invitro. METHODS: In this study, naloxone-precipitated morphine withdrawal
      syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to
      assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping
      and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake,
      sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain
      malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2))
      were assessed. RESULTS: Naloxone has significantly increased morphine withdrawal
      syndrome, both invivo and invitro. Insulin and gliclazide have significantly
      attenuated, naloxone induced behavioral changes like jumping and rearing
      frequency, forepaw licking, wet dog shake, sneezing, straightening, circling,
      OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH,
      nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro,
      insulin and gliclazide have significantly reduced naloxone-induced contraction in
      morphine-withdrawn rat ileum preparation. CONCLUSIONS: Insulin and gliclazide
      (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal
      syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may
      provide new avenues for research in morphine withdrawal.

PMID- 25059541
TI  - A novel fibroblast growth factor receptor family member promotes neuronal
      outgrowth and synaptic plasticity in aplysia.
AB  - Fibroblast Growth Factor (FGF) Receptors (FGFRs) regulate essential biological
      processes, including embryogenesis, angiogenesis, cellular growth and memory
      related long-term synaptic plasticity. Whereas canonical FGFRs depend exclusively
      on extracellular Immunoglobulin (Ig)-like domains for ligand binding, other
      receptor types, including members of the tropomyosin-receptor-kinase (Trk)
      family, use either Ig-like or Leucine-Rich Repeat (LRR) motifs, or both. Little
      is known, however, about the evolutionary events leading to the differential
      incorporation of LRR domains into Ig-containing tyrosine kinase receptors.
      Moreover, although FGFRs have been identified in many vertebrate species, few
      reports describe their existence in invertebrates. Information about the
      biological relevance of invertebrate FGFRs and evolutionary divergences between
      them and their vertebrate counterparts is therefore limited. Here, we
      characterized ApLRRTK, a neuronal cell-surface protein recently identified in
      Aplysia. We unveiled ApLRRTK as the first member of the FGFRs family deprived of
      Ig-like domains that instead contains extracellular LRR domains. We describe that
      ApLRRTK exhibits properties typical of canonical vertebrate FGFRs, including
      promotion of FGF activity, enhancement of neuritic outgrowth and signaling via
      MAPK and the transcription factor CREB. ApLRRTK also enhanced the synaptic
      efficiency of neurons known to mediate in vivo memory-related defensive
      behaviors. These data reveal a novel molecular regulator of neuronal function in
      invertebrates, provide the first evolutionary linkage between LRR proteins and
      FGFRs and unveil an unprecedented mechanism of FGFR gene diversification in
      primeval central nervous systems. 

PMID- 25059542
TI  - Pure ocular mucous membrane pemphigoid reactive with both beta4 integrin and the
      BP180 C-terminal domain.

PMID- 25059540
TI  - Extended access nicotine self-administration with periodic deprivation increases
      immature neurons in the hippocampus.
AB  - RATIONALE: Limited access nicotine self-administration decreases hippocampal
      neurogenesis, providing a mechanism for the deleterious effects of nicotine on
      hippocampal neuronal plasticity. However, recent studies have shown that limited
      access nicotine self-administration does not exhibit key features of nicotine
      dependence such as motivational withdrawal and increased motivation for nicotine
      after deprivation. OBJECTIVES: The present study used extended access nicotine
      self-administration (0.03 mg/kg/infusion, 21 h/day, 4 days) with intermittent
      periods of deprivation (3 days) for 14 weeks, to test the hypothesis that this
      model enhances nicotine seeking and produces distinct responses in hippocampal
      neurogenesis when compared with limited access (1 h/day, 4 days) intake. Animals
      in the extended access group were either perfused prior to or following their
      final deprivation period, whereas animals in the limited access group were
      perfused after their last session. RESULTS: Limited- and extended access nicotine
      self-administration with periodic deprivation did not affect proliferation and
      differentiation of oligodendrocyte progenitors in the medial prefrontal cortex
      (mPFC). Conversely, extended access nicotine self-administration with periodic
      deprivation enhanced proliferation and differentiation of hippocampal neural
      progenitors. Furthermore, in the hippocampus, the number of differentiating
      NeuroD-labeled cells strongly and positively correlated with enhanced nicotine
      seeking in rats that experienced extended access nicotine self-administration.
      CONCLUSIONS: These findings demonstrate that extended versus limited access to
      nicotine self-administration differentially affects the generation of new
      oligodendroglia and new neurons during adulthood. The increases in the number of
      differentiating cells in extended access nicotine self-administering rats may
      consequently contribute to aberrant hippocampal neurogenesis and may contribute
      to maladaptive addiction-like behaviors dependent on the hippocampus.

PMID- 25059543
TI  - Edith Wharton's threshold phobia and two worlds.
AB  - The American novelist Edith Wharton suffered an unusual childhood neurotic
      symptom, a fear of crossing thresholds, a condition that might be called a
      "threshold phobia." This symptom is identified and examined in autobiographical
      material, letters, diaries, and selected literary fiction and nonfiction left by
      Wharton to arrive at a formulation not previously drawn together. A fascinating
      theme-living or being trapped between "two worlds"-runs through much of the
      writer's life and work. The phobia is related to this theme, and both can be
      linked more broadly to certain sexual conflicts in women. This understanding of
      Wharton's phobia, it is argued, throws new light on the developmental issues and
      conflicts related to the female "oedipal" or triadic phase, characterized by the
      need to negotiate the two worlds of mother and of father. 

PMID- 25059544
TI  - Grip on challenging behavior: process evaluation of the implementation of a care
      program.
AB  - BACKGROUND: The Grip on Challenging Behavior care program for managing
      challenging behavior was implemented in the dementia special care units of 17
      Dutch nursing homes. A process evaluation of the implementation of the care
      program was performed to determine the quality of the implementation and the
      lessons to be learned for future implementation. METHODS: The care program was
      implemented according to a stepped wedge design. First-order data (data on
      recruitment, reach, relevance and feasibility) were used to determine the
      validity of the study, and second-order data (intervention quality and the
      barriers and facilitators for implementing the care program) were used to
      describe the implementation process. Two structured questionnaires were
      administered to care staff and key stakeholders and semi-structured interviews
      were held in the units. RESULTS: University affiliated and non-affiliated nursing
      homes from different parts of the Netherlands participated. The resident
      participation rate was over 95% and the participation rate for the training
      sessions was 82%. Respondents considered the care program relevant and feasible.
      The degree of implementation was not optimal. The barriers and facilitators in
      implementing the care program could be divided into three categories:
      organizational aspects, culture on the unit and aspects of the care program
      itself. CONCLUSIONS: The recruitment, reach, relevance and feasibility are
      sufficient to allow for analysis and generalization of the effects of the care
      program, but the degree of implementation should be taken into account in further
      analysis. Future projects that involve implementation should consider the
      specific features of the organization and the cultural orientation of the unit to
      better adapt to specific needs. TRIAL REGISTRATION: The Netherlands National
      Trial register under number NTR2141 registered on 11 December 2009. Randomization
      took place in November 2010, and the first intervention group started using the
      intervention in February 2011.

PMID- 25059545
TI  - UVB irradiation enhances TiO2 nanoparticle-induced disruption of calcium
      homeostasis in human lens epithelial cells.
AB  - Currently, titanium dioxide nanoparticles (TiO2 NPs) have been widely used in
      various applications including cosmetics, food additives and biomedicine.
      However, there are few reports available using TiO2 NPs to treat ocular diseases.
      Posterior capsular opacification (PCO) is the most frequent complication after
      cataract surgery, which is induced by the proliferation and migration of lens
      epithelial cells. Thus, inhibiting the proliferation of lens epithelial cells
      will efficiently reduce the occurrence of PCO. In this study, we investigated the
      effects of TiO2 NPs on HLE B-3 cells with or without ultraviolet B (UVB)
      irradiation in vitro. We found that TiO2 NPs can inhibit HLE B-3 cell growth,
      cause the elevation of intracellular [Ca(2+)], produce excessive reactive oxygen
      species (ROS), further reduce Ca(2+)-ATPase activity and decrease the expression
      of plasma membrane calcium ATPase 1 (PMCA1), finally disrupt the intracellular
      calcium homeostasis and induce cell damage. Importantly, UVB irradiation can
      apparently enhance these effects on HLE B-3 cells in the presence of TiO2 NPs.
      Taken together, the generation of excessive ROS and the disruption of
      intracellular calcium homeostasis may be both involved in TiO2 nanoparticle
      induced HLE B-3 cell damage under UVB irradiation.

PMID- 25059546
TI  - Andrographolide radiosensitizes human esophageal cancer cell line ECA109 to
      radiation in vitro.
AB  - To explore the radiosensitivity of andrographolide on esophageal cancer cell line
      ECA109. The inhibition effects of andrographolide were measured using 3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Clonogenic
      survival assay was used to evaluate the effects of andrographolide on the
      radiosensitivity of esophageal cancer cells. Immunofluorescence was employed to
      examine Bax expression. The changes in cell cycle distribution and apoptosis were
      assayed using flow cytometry. The expression of NF-kappab/Cleaved
      Caspase3/Bax/Bcl-2 was measured using Western blot analysis. DNA damage was
      detected via gamma-H2AX foci counting. With a clear dose and time effects,
      andrographolide was found to inhibit the proliferation of esophageal cell line
      ECA109. The results of the clonogenic survival assay show that andrographolide
      could markedly enhance radiosensitivity (P < 0.05) with a sensitizing enhancement
      ratio of 1.28. Andrographolide caused a dose-dependent increase in Cleaved
      Caspase3/Bax protein expression and a decrease in Bcl-2/NF-kappab expression.
      Apoptosis in andrographolide-treated ECA-109 increased significantly compared
      with the apoptosis in the simple drug and radiation combined with drug groups (P
      < 0.001; P < 0.05). Moreover, compared with the independent radiation group, the
      andrographolide combined with radiation group increased the number of DNA double
      chain breaks. Andrographolide can increase the radiosensitivity of esophageal
      cell line ECA109. This result may be associated with the decrease in the NF
      kappab level and the induced apoptosis of esophageal cancer cells. 

PMID- 25059547
TI  - Synthesis of new thiazolo[4,5-d]pyrimidines as Corticotropin releasing factor
      modulators.
AB  - Corticotropin-releasing factor (CRF) is a neurohormone that plays a crucial role
      in integrating the body's overall response to stress. It appears necessary and
      sufficient for the organism to mount functional, physiological and endocrine
      responses to stressors. CRF is released in response to various triggers such as
      chronic stress. The role of CRF and its involvement in these neurological
      disorders suggest that new drugs that can target the CRF function or bind to its
      receptors may represent a new development of neuropsychiatric medicines to treat
      various stress-related disorders including depression, anxiety and addictive
      disorders. Based on pharmacophore of the CRF1 receptor antagonists, a new series
      of thiazolo[4,5-d] pyrimidines were synthesized as Corticotropin-releasing factor
      (CRF) receptor modulators and the prepared compounds carry groups shown to
      produce optimum binding affinity to CRF receptors. Twenty two compounds were
      evaluated for their CRF1 receptor binding affinity in HEK 293 cell lines and two
      compounds 5o and 5s showed approximately 25% binding affinity to CRF1 receptors.
      Selected compounds (5c and 5f) were also evaluated for their effect on expression
      of genes associated with depression and anxiety disorders such as CRF1, CREB1,
      MAO-A, SERT, NPY, DatSLC6a3, and DBH and significant upregulation of CRF1 mRNA
      has been observed with compound 5c. 

PMID- 25059548
TI  - Automatic computation of left ventricular volume changes over a cardiac cycle
      from echocardiography images by nonlinear dimensionality reduction.
AB  - Curve of left ventricular (LV) volume changes throughout the cardiac cycle is a
      fundamental parameter for clinical evaluation of various cardiovascular diseases.
      Currently, this evaluation is often performed manually which is tedious and time
      consuming and suffers from significant interobserver and intraobserver
      variability. This paper introduces a new automatic method, based on nonlinear
      dimensionality reduction (NLDR) for extracting the curve of the LV volume changes
      over a cardiac cycle from two-dimensional (2-D) echocardiography images.
      Isometric feature mapping (Isomap) is one of the most popular NLDR algorithms. In
      this study, a modified version of Isomap algorithm, where image to image distance
      metric is computed using nonrigid registration, is applied on 2-D
      echocardiography images of one cycle of heart. Using this approach, the nonlinear
      information of these images is embedded in a 2-D manifold and each image is
      characterized by a symbol on the constructed manifold. This new representation
      visualizes the relationship between these images based on LV volume changes and
      allows extracting the curve of the LV volume changes automatically. Our method in
      comparison to the traditional segmentation algorithms does not need any LV
      myocardial segmentation and tracking, particularly difficult in the
      echocardiography images. Moreover, a large data set under various diseases for
      training is not required. The results obtained by our method are quantitatively
      evaluated to those obtained manually by the highly experienced echocardiographer
      on ten healthy volunteers and six patients which depict the usefulness of the
      presented method. 

PMID- 25059550
TI  - Loss of GluN2A-containing NMDA receptors impairs extra-dimensional set-shifting.
AB  - Glutamate neurotransmission via the N-methyl-D-aspartate receptor (NMDAR) is
      thought to mediate the synaptic plasticity underlying learning and memory
      formation. There is increasing evidence that deficits in NMDAR function are
      involved in the pathophysiology of cognitive dysfunction seen in neuropsychiatric
      disorders and addiction. NMDAR subunits confer different physiological properties
      to the receptor, interact with distinct intracellular postsynaptic scaffolding
      and signaling molecules, and are differentially expressed during development.
      Despite these known differences, the relative contribution of individual subunit
      composition to synaptic plasticity and learning is not fully elucidated. We have
      previously shown that constitutive deletion of GluN2A subunit in the mouse
      impairs discrimination and re-learning phase of reversal when exemplars are
      complex picture stimuli, but spares acquisition and extinction of non
      discriminative visually cued instrumental response. To investigate the role of
      GluN2A containing NMDARs in executive control, we tested GluN2A knockout
      (GluN2A(KO) ), heterozygous (GluN2A(HET) ) and wild-type (WT) littermates on an
      attentional set-shifting task using species-specific stimulus dimensions. To
      further explore the nature of deficits in this model, mice were tested on a
      visual discrimination reversal paradigm using simplified rotational stimuli.
      GluN2A(KO) were not impaired on discrimination or reversal problems when tactile
      or olfactory stimuli were used, or when visual stimuli were sufficiently easy to
      discriminate. GluN2A(KO) showed a specific and significant impairment in
      ventromedial prefrontal cortex-mediated set-shifting. Together these results
      support a role for GluN2A containing NMDAR in modulating executive control that
      can be masked by overlapping deficits in attentional processes during high task
      demands.

PMID- 25059551
TI  - Biochemical and histopathological evaluations of ghrelin effects following
      cadmium toxicity in the rat testis.
AB  - Numerous reports demonstrate that cadmium (Cd) induces oxidative stress by
      increasing lipid peroxidation and altering antioxidative enzymes status. Thirty
      male rats were subdivided into control-saline, Cd-saline and Cd-ghrelin groups. A
      single dose of Cd was injected to induce testicular injury and also ghrelin for
      10 consecutive days to group 3. SOD activity decreased and lipid peroxidation
      increased by Cd administration. The mean activities of GPx and CAT as well as GSH
      content were lower in the Cd-saline rats; however, they did not statistically
      differ compared with the controls. Exposure to Cd resulted in complete
      degeneration of seminiferous tubules with severe depletion of germ cells and
      arrest in spermatogenesis. Notably, ghrelin treatment not only prevented
      reduction in SOD, GPx, CAT and GSH level, but also increased enzyme activities
      form their normal values. Moreover, TBARS concentration was significantly reduced
      by ghrelin administration. Furthermore, ghrelin pre-treatment resulted in partial
      but not significant prevention in testicular histopathological features damaged
      by Cd. In conclusion, the obtained results indicate for the first time the novel
      evidences of ghrelin ability in promotion of antioxidant enzyme activities and
      reduction of lipid peroxidation following Cd-induced oxidative stress in the rat
      testis. These observations also demonstrate that ghrelin may be considered as
      promising antioxidant agent in prevention and attenuation of testicular injury
      upon Cd toxicity. 

PMID- 25059552
TI  - Efficacy of daclatasvir in hepatitis C virus.
AB  - Daclatasvir is a novel NS5A inhibitor of hepatitis C virus (HCV). Daclatasvir
      combined with peginterferon alpha-2a and ribavirin in Japanese patients infected
      with genotype 1b HCV achieved sustained virological response (SVR) in 100% of
      treatment-naive patients, due to high rates of favorable IL28B allele and
      genotype 1b. SVR 24 was achieved by asunaprevir and daclatasvir in 87.4% of
      intolerant and 80.5% of nonresponder patients. Baseline NS5A-resistant variants
      were detected and they failed to achieve SVR. Most patients with genotype 1a
      experienced virological breakthrough by dual oral treatment, and should be
      treated QUAD or replaced by all oral regimens that are more potent and have fewer
      side effects. IFN-free regimens including daclatasvir and asunaprevir for
      genotype 1 null responders should be tailored to subtype, and preexisting NS5A
      resistant variants should be evaluated carefully before choosing the drugs. This
      regimen alone is unlikely to move forward without additional agents. 

PMID- 25059553
TI  - Public perceptions of cancer risk factors: a Western Australian study.
AB  - ISSUE ADDRESSED: People's perceptions of risk may influence health-related
      behaviours. The aim of this study was to investigate the perception of cancer
      risk factors among Western Australian adults in order to inform health promotion
      policies. METHODS: Cross-sectional surveys of 2094 adults were undertaken in
      2007/2008 in which respondents were asked whether they thought factors increased
      or decreased the risk of cancer. Factors included both established and
      unestablished risk factors for cancer. The distribution of perceptions was
      compared according to age and sex. RESULTS: The study found high levels of
      endorsement for some unestablished risk factors (74-91%) and comparatively lower
      levels of endorsement for many established risk factors (33-80%). The established
      risk factors of smoking and asbestos received high levels of endorsement (94
      98%). CONCLUSION: It appears that the alignment between scientifically
      established risk factors and the Western Australian public's perception of cancer
      risk factors could be improved. SO WHAT? Health promotion strategies are needed
      to improve the public's awareness of cancer risk factors. The high levels of
      endorsement attributed to unestablished risk factors highlight the need to dispel
      myths surrounding cancer and to reinforce the key factors in cancer prevention.
      Ongoing assessment of the alignment between community perceptions of cancer risk
      and the scientific evidence for cancer risk is important for guiding
      prioritisation within public health organisations.

PMID- 25059554
TI  - Nicotine induces the production of IL-1beta and IL-8 via the alpha7 nAChR/NF
      kappaB pathway in human periodontal ligament cells: an in vitro study.
AB  - BACKGROUND/AIMS: Tobacco smoking is a major risk factor for the occurrence and
      progression of periodontitis. We previously demonstrated that nicotine could
      induce the expression of alpha7 nicotinic acetylcholine receptors (alpha7 nAChR)
      in human and rat periodontal tissues. To further examine the signal pathways
      mediated by alpha7 nAChR in periodontal ligament (PDL) cells, we investigated
      whether nicotine affects interleukin-1beta (IL-1beta) and interleukin-8 (IL-8)
      via the alpha7 nAChR/NF-kappaB pathway in human PDL cells. METHODS: Human PDL
      cells were pre-incubated with alpha-bungarotoxin (alpha-BTX) or pyrrolidine
      dithiocarbamate (PDTC), then cultured with nicotine. Then, we used western
      blotting, a dual-luciferase reporter, real-time quantitative PCR and an enzyme
      linked immunoassay to assess expression of the NF-kappaB p65 subunit, NF-kappaB
      activity and production of IL-1beta and IL-8 in human PDL cells. RESULTS:
      Compared with the control group, nicotine could significantly induce production
      of IL-1beta and IL-8 in human PDL cells and cause the similar effects on the
      expression of the NF-kappaB p65 subunit and NF-kappaB activity. CONCLUSION: This
      study demonstrates that nicotine could induce production of IL-1beta and IL-8 via
      the alpha7 nAChR/NF-kappaB pathway in human PDL cells, providing data for a
      better understanding of the relationships among smoking, nicotine, and
      periodontitis.

PMID- 25059555
TI  - Evaluation of miR-216a and miR-217 as potential biomarkers of acute pancreatic
      injury in rats and mice.
AB  - Mild injury of the exocrine pancreas is often asymptomatic and can be under- or
      mis-diagnosed. The pancreas-enriched microRNAs miR-216a and miR-217 were
      evaluated as potential serum biomarkers of exocrine pancreas injury in rodent
      models of acute pancreatitis induced by caerulein, l-arginine, and pancreatic
      duct ligation. Both microRNAs showed time- and dose- relevant responses to
      pancreatic injury and wider dynamic ranges of response than serum amylase or
      lipase. Pancreas-selective microRNAs were found to be relatively sensitive serum
      biomarkers of pancreatic injury in rodents with potentially greater specificity
      than the current standard assays.

PMID- 25059556
TI  - Longitudinal in vivo MR imaging of live earthworms.
AB  - Earthworm (Oligochaeta, Lumbricidae) species are used widely in eco-toxicological
      tests especially with contaminated soils. These long-term tests are reliable, but
      a high sample size is needed. Magnetic resonance imaging (MRI) can produce fast,
      robust, sensitive, and longitudinal morphological results using a small sample
      size. Performing longitudinal in vivo examinations of earthworms using MRI
      requires the need for anesthetics to completely avoid earthworm's moving. Our
      goal was to develop a simple and non-invasive method to anesthetize earthworms
      for in vivo longitudinal imaging studies. We investigated a number of different
      anesthesia methods and found that propan-2-ol and its vapor was optimal. We used
      a commercial sequential nanoScan(r) PET/MRI system (Mediso Ltd, Hungary,
      Budapest) to explore feasibility of MR imaging in immobilized earthworms. It was
      possible to visualize via micro MRI the brain, gastrointestinal tract, seminal
      vesicles, calciferous gland (Morren gland), and main blood vessels of the
      circulatory system. Our findings show the possibilities to examine changes in
      morphology using MRI of certain organs using a reversible, long-term
      immobilization method.

PMID- 25059557
TI  - Hitchhiking of host biology by beneficial symbionts enhances transmission.
AB  - Transmission plays a key role in the evolution of symbiosis. Mixed mode
      transmission combines horizontal and vertical mechanisms for symbiont
      acquisition. However, features that enable mixed transmission are poorly
      understood. Here, we determine the mechanistic basis for the recruitment of the
      beneficial bacterium, Aeromonas veronii by the leech, Hirudo verbana. We
      demonstrate that host mucosal secretions complement imperfect symbiont vertical
      transmission. First, we show that the A. veronii population within secretions
      originates from the host digestive tract and proliferates synchronously with
      shedding frequency, demonstrating the coupling of partner biology. Furthermore,
      leeches are attracted to these castings with oral contact proving sufficient for
      symbiont transmission. Leech attraction to mucus is not affected by the symbiont
      state of either the host or mucus, suggesting that A. veronii exploits
      preexisting host behavior and physiological traits. A dual transmission mode,
      integrating multiple layers of host contributions, may prove evolutionarily
      advantageous for a wide range of symbioses. Using such a strategy, host infection
      is ensured, while also providing access to a higher genetic diversity of
      symbionts. Countless host-associated microbes exhibit mixed mode transmission,
      supporting the use of the leech symbiosis as a model for enhancing our
      understanding of the specificity, establishment and persistence of microbiotas. 

PMID- 25059558
TI  - Suddenly included: cultural differences in experiencing re-inclusion.
AB  - In the current research, we examined whether re-inclusion (i.e. the change from a
      previous state of exclusion to a new state of inclusion) was perceived
      differently by people with individualistic and collectivistic cultural
      backgrounds. Individualists (German and Austrian participants) but not
      collectivists (Chinese participants) experienced re-inclusion differently than
      continued inclusion: While collectivistic participants did not differentiate
      between both kinds of inclusion, individualistic participants showed reduced
      fulfilment of their psychological needs under re-inclusion compared to continued
      inclusion. The results moreover revealed that only participants from
      individualistic cultures expressed more feelings of exclusion when re-included
      than when continually included. These exclusionary feelings partially mediated
      the relationship between the different states of inclusion and basic need
      fulfilment. 

PMID- 25059559
TI  - The hydrophobic force: measurements and methods.
AB  - The hydrophobic force describes the attraction between water-hating molecules
      (and surfaces) that draws them together, causing aggregation, phase separation,
      protein folding and many other inherent physical phenomena. Attempts have been
      made to isolate the range and magnitude of this interaction between extended
      surfaces for more than four decades, with wildly varying results. In this
      perspective, we critically analyse the application of common force-measuring
      techniques to the hydrophobic force conundrum. In doing so, we highlight possible
      interferences to these measurements and provide physical rationalisation where
      possible. By analysing the most recent measurements, new approaches to
      establishing the form of this force become apparent, and we suggest potential
      future directions to further refine our understanding of this vital, physical
      force. 

PMID- 25059560
TI  - Affinity polymers tailored for the protein A binding site of immunoglobulin G
      proteins.
AB  - Rational design in combination with a screening process was used to develop
      affinity polymers for a specific binding site on the surface of immunoglobulin G
      (IgG) proteins. The concept starts with the identification of critical amino acid
      residues on the protein interface and their topological arrangement. Appropriate
      binding monomers were subsequently synthesized. Together with a sugar monomer (2
      5 equiv) for water solubility and a dansyl monomer (0.5 equiv) as a fluorescent
      label, they were subjected in aqueous solution to linear radical copolymerization
      in various compositions (e.g., azobisisobutyronitrile (AIBN), homogeneous
      water/DMF mixtures). After ultrafiltration and lyophilization, colorless dry
      water-soluble powders were obtained. NMR spectroscopic and gel permeation
      chromatography (GPC) characterization indicated molecular weights between 30 and
      500 kD and confirmed retention of monomer composition as well as the absence of
      monomers. In a competitive enzyme-linked immunosorbent assay (ELISA) screen of
      the polymer libraries (20-50 members), few copolymers qualified as strong and
      selective binders for the protein A binding site on the Fc fragment of the
      antibody. Their monomer composition precisely reflected the critical amino acids
      found at the interface. The simple combination of a charged and a nonpolar
      binding monomer sufficed for selective submicromolar IgG recognition by the
      synthetic polymer. Affinities were confirmed by fluorescence titrations; they
      increased with decreasing salt load but remained largely unaltered at lowered pH.
      Other proteins, including those of similar size and isoelectric point (pI), were
      bound 10-1000 times less tightly. This example indicates that interaction domains
      in other proteins may also be targeted by synthetic polymers if their comonomer
      composition reflects the nature and arrangement of amino acid residues on the
      protein surface. 

PMID- 25059561
TI  - Reasons for entering treatment reported by initially treatment-resistant patients
      with substance use disorders.
AB  - Many individuals with substance use disorders are resistant to entering formal
      treatment, despite the negative consequences that plague their own lives and the
      lives of concerned significant others (CSOs). Community Reinforcement and Family
      Training (CRAFT) has been developed as an effective strategy for helping family
      members who are concerned about the alcohol/drug use of a loved one who refuses
      to seek treatment. The present study explored reasons and feelings that played a
      part in these resistant individuals' (identified patients [IPs]) decision to
      begin treatment. Written statements and feelings of 36 initially treatment
      refusing IPs, who were engaged into treatment via their CRAFT-trained CSOs, were
      examined upon entering treatment. Self-report forms assessed three complementary
      domains about entering treatment: (1) feelings about coming for treatment, (2)
      important reasons for entering treatment, and (3) reasons for entering treatment
      narratives. It was shown that the occurrences of self-reported positive emotions
      and statements that expressed a positive wish for change outweighed negative
      feelings and statements. Although conceivably these CRAFT-exposed IPs may have
      provided different responses than other treatment-seeking populations, the
      current study's strong IP reports of positive feelings, reasons, and narrative
      statements regarding treatment entry nonetheless address potential concerns that
      treatment-refusing IPs might only enter treatment if felt coerced by family
      members and while experiencing salient negative feelings overall. 

PMID- 25059562
TI  - The T657C polymorphism on the SYCP3 gene is associated with recurrent pregnancy
      loss.
AB  - SYCP3 (Sinaptonemal complex protein 3) plays a critical role in pairing and
      recombination of homologous chromosomes in meiosis 1. It has been shown that lack
      of this gene leads to infertility in male and weakened fertility in female mice.
      In a case-control study, we investigated the SYCP3T657C polymorphism in the
      genome of 100 Iranian women with recurrent pregnancy losses of unknown causes as
      well as 100 control samples of normal fertile women having at least one healthy
      child. The general aim of our study was to determine whether there is a
      relationship between genetic changes in the SYCP3 gene and recurrent pregnancy
      loss in human or not. Frequency of the heterozygous genotype and mutated allele C
      were significantly higher in women with recurrent pregnancy losses (P-value <
      0.005). Our findings suggest that the T657C polymorphism of the SYCP3 gene is
      possibly associated with recurrent pregnancy loss of unknown cause in human. 

PMID- 25059563
TI  - Twists and turns in the business of gonadal stem cells.

PMID- 25059564
TI  - Elevated intracranial dopamine impairs the glutamate-nitric oxide-cyclic
      guanosine monophosphate pathway in cortical astrocytes in rats with minimal
      hepatic encephalopathy.
AB  - In a previous study by our group memory impairment in rats with minimal hepatic
      encephalopathy (MHE) was associated with the inhibition of the glutamate-nitric
      oxide-cyclic guanosine monophosphate (Glu-NO-cGMP) pathway due to elevated
      dopamine (DA). However, the effects of DA on the Glu-NO-cGMP pathway localized in
      primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In
      the present study, it was identified that when the levels of DA in the cerebral
      cortex of rats with MHE and high-dose DA (3 mg/kg)-treated rats were increased,
      the co-localization of N-methyl-d-aspartate receptors subunit 1 (NMDAR1),
      calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC)
      and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein
      (GFAP), a marker protein of astrocytes, all significantly decreased, in both the
      MHE and high-dose DA-treated rats (P<0.01). Furthermore, NMDA-induced
      augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in
      PCAs was decreased in MHE and DA-treated rats, as compared with the controls.
      Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose
      dependent decrease in the concentration of intracellular calcium, nitrites and
      nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and
      sGC/cGMP. High doses of DA (50 uM) significantly reduced NMDA-induced
      augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC
      and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu-NO
      cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE.

PMID- 25059565
TI  - Self-assembly of ferromagnetic organic-inorganic perovskite-like films.
AB  - Perovskite-based organic-inorganic hybrids hold great potential as active layers
      in electronics or optoelectronics or as components of biosensors. However, many
      of these applications require thin films grown with good control over structure
      and thickness--a major challenge that needs to be addressed. The work presented
      here is an effort towards this goal and concerns the layer-by-layer deposition at
      ambient conditions of ferromagnetic organic-inorganic hybrids consisting of
      alternating CuCl4-octahedra and organic layers. The Langmuir-Blodgett technique
      used to assemble these structures provides intrinsic control over the molecular
      organization and film thickness down to the molecular level. Magnetic
      characterization reveals that the coercive field for these thin films is larger
      than that for solution-grown layered bulk crystals. The strategy presented here
      suggests a promising cost effective route to facilitate the excellently
      controlled growth of sophisticated materials on a wide variety of substrates that
      have properties relevant for the high density storage media and spintronic
      devices.

PMID- 25059566
TI  - Diagnosis of influenza: only a problem of coding?
AB  - OBJECTIVE: To evaluate the characteristics of hospital discharge diagnoses of
      influenza measured by using specific International Classification of Diseases,
      9th Revision, Clinical Modification (ICD-9 CM) codes. SUBJECTS AND METHODS: The
      study was conducted for the 3 years 2007, 2008 and 2011. The database included
      (1) administrative and clinical data on Sicilian patients admitted to acute care
      hospitals and (2) data from the influenza virological surveillance of 10 European
      countries (FluNet database). All Sicilian patients diagnosed with at least 1 ICD
      9 CM code for influenza (487.0, 487.1 and 487.9) were considered influenza cases.
      RESULTS: Overall, 2,880 patients with an ICD-9 CM code attributable to influenza
      were hospitalized in Sicily: 2,119 (73.6%) were admitted from November to April,
      whereas 761 (26.4%) were admitted from May to October. In the 3 years studied,
      the analyzed European influenza surveillance systems recorded a peak of
      laboratory-confirmed influenza activity from November to April with 36,753
      (99.7%) influenza cases, whereas only 124 cases (0.3%) were observed from May to
      October. CONCLUSIONS: In Sicily, more than one quarter of all hospital admissions
      with an ICD-9 CM code for influenza were observed in the months with a negligible
      circulation of influenza viruses. Our findings show that several hospital
      discharge records included ICD-9 CM codes for influenza with low levels of
      sensitivity, specificity and/or appropriateness for clinical information and
      support the need for improving medical education on the epidemiology and hospital
      management of influenza cases.

PMID- 25059567
TI  - SMA carrier testing: a meta-analysis of differences in test performance by ethnic
      group.
AB  - INTRODUCTION: Spinal muscular atrophy (SMA) is a severe autosomal recessive
      genetic disease that occurs in about one in every 10 000 births. Prenatal carrier
      testing is available for SMA, and the utility of universal screening is actively
      debated. OBJECTIVE: The aim of this study was to perform a systematic review and
      meta-analysis of SMA genotype frequency, carrier frequency, and carrier test
      performance in different ethnic groups. METHODS: We performed a systematic review
      of the literature for studies on SMA carrier screening test performance.
      Ethnicity-specific allele frequencies, carrier rates, and screening test
      performance were determined from data of 169 000 individuals in 14 published
      studies. Pooled estimates were calculated for each ethnic group using a random
      effects meta-analysis. RESULTS: The detection rate of SMA screening in the non
      Black population was 87-95%; however, detection rates fell to 71% among the Black
      population. CONCLUSION: These results highlight that although SMA carrier testing
      generally performs well and could be considered as a routine prenatal screen, SMA
      testing should be used cautiously in the Black population.

PMID- 25059568
TI  - Glycyrrhizic acid ameliorates HMGB1-mediated cell death and inflammation after
      renal ischemia reperfusion injury.
AB  - BACKGROUND: Renal ischemia reperfusion injury (IRI) leads to acute kidney injury
      (AKI) and the death of tubular epithelial cells (TEC). The release of high
      mobility group box-1 (HMGB1) and other damage-associated molecular pattern
      moieties from dying cells may promote organ dysfunction and inflammation by
      effects on TEC. Glycyrrhizic acid (GZA) is a functional inhibitor of HMGB1, but
      its ability to attenuate the HMGB1-mediated injury of TEC has not been tested.
      METHODS/RESULTS: In vitro, hypoxia and cytokine treatment killed TEC and resulted
      in the progressive release of HMGB1 into the supernatant. GZA reduced the hypoxia
      induced TEC death as measured by annexin-V and propidium iodide. Hypoxia
      increased the expression of MCP-1 and CXCL1 in TEC, which was reduced by GZA in a
      dose-dependent manner. Similarly, the HMGB1 activation of effector NK cells was
      inhibited by GZA. To test the effect of HMGB1 neutralization by GZA in vivo, mice
      were subjected to renal IRI. HMGB1 protein expression increased progressively in
      kidneys from 4 to 24 h after ischemia and was detected in tubular cells by 4 h
      using immunohistochemistry. GZA preserved renal function after IRI and reduced
      tubular necrosis and neutrophil infiltration by histological analyses and
      ethidium homodimer staining. CONCLUSIONS: Importantly, these data demonstrate for
      the first time that AKI following hypoxia and renal IRI may be promoted by HMGB1
      release, which can reduce the survival of TEC and augment inflammation.
      Inhibition of the interaction of HMGB1 with TEC through GZA may represent a
      therapeutic strategy for the attenuation of renal injury following IRI and
      transplantation.

PMID- 25059569
TI  - Preoptic inputs and mechanisms that regulate maternal responsiveness.
AB  - The preoptic area is a well-established centre for the control of maternal
      behaviour. An intact medial preoptic area (mPOA) is required for maternal
      responsiveness because lesion of the area abolishes maternal behaviours. Although
      hormonal changes in the peripartum period contribute to the initiation of
      maternal responsiveness, inputs from pups are required for its maintenance.
      Neurones are activated in different parts of the mPOA in response to pup
      exposure. In the present review, we summarise the potential inputs to the mPOA of
      rodent dams from the litter that can activate mPOA neurones. The roles of
      potential indirect effects through increased prolactin levels, as well as
      neuronal inputs to the preoptic area, are described. Recent results on the
      pathway mediating the effects of suckling to the mPOA suggest that neurones
      containing the neuropeptide tuberoinfundibular peptide of 39 residues in the
      posterior thalamus are candidates for conveying the suckling information to the
      mPOA. Although the molecular mechanism through which these inputs alter mPOA
      neurones to support the maintenance of maternal responding is not yet known,
      altered gene expression is a likely candidate. Here, we summarise gene expression
      changes in the mPOA that have been linked to maternal behaviour and explore the
      idea that chromatin remodelling during mother-infant interactions mediates the
      long-term alterations in gene expression that sustain maternal responding. 

PMID- 25059570
TI  - An analysis of influenza prevention measures from air travellers' perspective.
AB  - BACKGROUND: The influenza A virus is easily transmitted through airborne saliva
      droplets disseminated by unprotected coughing or sneezing, particularly in a
      crowded, enclosed space. AIM: The purpose of this study was to analyse the
      knowledge, attitudes and practices of air travellers regarding influenza A
      preventive measures and to examine any significant differences in perceptions
      among different types of traveller groups. METHODS: This study used a 5-point
      Likert scale questionnaire and surveyed 1684 passengers at Taoyuan International
      Airport in Taiwan. The frequencies, mean score and ranking of descriptive
      analyses were used to evaluate respondents' demographic profiles. t-Test, one-way
      analysis of variance and Scheffe post hoc analyses were used to evaluate the
      relationship among knowledge, attitudes and practices, and respondents'
      characteristics. RESULTS: There were significant differences in the knowledge,
      attitudes and practices measures among groups with different types of trip
      purposes and among occupation groups. Most passengers expressed common knowledge
      regarding influenza A; however, their attitudes and their degree of perception
      were not consistent with their prevention practices. LIMITATIONS: This research
      is limited because it only examined surveyed air travellers in Taiwan.
      CONCLUSION: Air travellers could benefit greatly if the government and airlines
      were to implement a health policy that includes education on the importance of
      influenza prevention measures, such as frequent hand washing, to citizens. Nurses
      could be involved in this important health promotion activity. IMPLICATIONS FOR
      NURSING AND HEALTH POLICY: Schools should implement a health education policy to
      communicate the importance of prevention measures. Nurses can consider how they
      can be involved in emphasizing the importance of prevention and health promotion
      regarding this. Airlines should also include basic preventive measures as a
      component of flight attendant training.

PMID- 25059571
TI  - Associations Between Family of Origin Climate, Relationship Self-Regulation, and
      Marital Outcomes.
AB  - Using dyadic data from 961 married couples from the Relationship Evaluation
      Questionnaire project, the current study explored the direct association between
      family of origin climate and marital outcomes and the indirect association via
      relationship self-regulation (RSR). Results from the actor-partner
      interdependence model analysis indicated that family of origin climate was
      positively associated with marital stability directly and indirectly via the
      effects of RSR and marital satisfaction for both men and women. Results suggest
      that the experience one has in their family of origin is associated with their
      marital outcomes through their RSR. Actor-partner direct and indirect effects
      indicate that spouses' RSR may have important consequences for both partner's
      evaluation of the marriage. Implications for intervention and future research are
      discussed. 

PMID- 25059572
TI  - In vitro antioxidant activities and anti-proliferative properties of the
      functional herb Abrus cantoniensis and its main alkaloid abrine.
AB  - Abrus cantoniensis is a common and popular vegetative food consumed as beverage,
      soup and folk medicine in the tropical and subtropical areas of Asia. It has been
      claimed valuable for cleansing toxicants in the liver. However, the functional
      effects of A. cantoniensis have not yet been scientifically explored. This study
      comprehensively evaluated the in vitro antioxidant and anti-proliferative
      capacities of the herbal extract and the main alkaloid abrine. Abrine was
      qualitatively and quantitatively determined in methanol extract (ME) using HPLC
      DAD and LC-MS/MS. The results showed that ME, ethyl acetate fraction (EF) and
      abrine exhibited comparable ABTS radical cation scavenging activities and
      reducing power to two commercial antioxidants (BHT and Trolox). The EF exerted
      strong cellular antioxidant activity and selective cytotoxicity against three
      cancer cell lines in a dose-dependent manner. Biological assays revealed that the
      EF induced cell cycle arrest at G2/M and apoptosis in MCF-7 and Hep3B cells after
      48 h of treatment. Thus, A. cantoniensis exerted potent cellular antioxidant and
      anti-proliferative properties, highlighting why it has been traditionally used as
      a functional food. 

PMID- 25059573
TI  - Prognostic relevance of Federation Nationale des Centres de Lutte Contre le
      Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a
      study of 50 cases.
AB  - Dedifferentiated liposarcoma represents a form of liposarcoma composed of a non
      lipogenic sarcoma associated with well-differentiated liposarcoma. The prognostic
      significance of histological grading of the dedifferentiated component remains to
      be elucidated due to vague grading criteria employed in previous studies.
      Molecular markers of tumor behavior, including amplification levels of murine
      double minute-2 (MDM2) and cyclin-dependent kinase-4 (CDK4) genes, have been
      explored in a limited number of cases. Here we investigate whether 'Federation
      Nationale des Centres de Lutte Contre le Cancer' (FNCLCC) grade and MDM2 gene
      amplification levels have prognostic value in dedifferentiated liposarcoma in
      terms of local recurrence and disease-specific survival. Fifty cases were
      retrieved, reviewed and FNCLCC grade was scored for the dedifferentiated
      component. Testing for MDM2 gene amplification was performed by fluorescence in
      situ hybridization. Amplification was categorized as high level (>=20 copies) and
      as low level (<20 copies). Follow-up data was obtained through chart review. Log
      rank test and Cox proportional hazard models were used to determine the effect of
      grade and level of MDM2 amplification on outcomes. Our series includes 50
      patients (male n=28, female n=22) with an average age of 63 years (range, 28-88)
      and a median follow-up of 28 months (range, 2-120). Tumors were graded as grade 1
      (6%), grade 2 (58%), and grade 3 (36%). When adjusted for age, sex, site, tumor
      size, and margin status, grade 3 patients had a higher recurrence rate than
      grades 1 and 2 (HR=2.07, 95% CI: 1.24, 7.62; P=0.015). Patients with high-level
      MDM2 amplification had higher recurrence rate on univariate analysis (P=0.028),
      but not on multivariate analysis (HR=1.69, 95% CI: 0.73, 3.94; P=0.221). FNCLCC
      grade 3 dedifferentiation confers a worse prognosis in dedifferentiated
      liposarcoma in terms of local recurrence. MDM2 amplification level remains a
      useful diagnostic tool in dedifferentiated liposarcoma, but has no prognostic
      value in terms of local recurrence. 

PMID- 25059574
TI  - Erratum to: Perceived messages about bone health after a fracture are not
      consistent across healthcare providers.

PMID- 25059575
TI  - Intravitreal functional plasminogen in eyes with branch retinal vein occlusion.
AB  - PURPOSE: To evaluate whether intravitreal functional plasminogen is elevated in
      eyes with branch retinal vein occlusion (BRVO) and to discover whether
      intravitreal plasminogen activities are correlated with the extent of blood
      retina barrier (BRB) breakdown. METHODS: Our study is a prospective case series
      of 20 consecutive patients with BRVO and 10 consecutive patients serving as
      controls. Vitreous taps were extracted from the central vitreous body and
      plasminogen was functionally determined in an innovative, ultrasensitive p
      nitroanilide reaction after activation with streptokinase (100% of normal, %N =
      functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF
      levels were assayed to estimate BRB breakdown. RESULTS: Intravitreal functional
      plasminogen was detected in all analyzed samples (n = 30) and mean (+/-SD)
      plasminogen activities were found to be 0.97 +/- 1.06%N (range: 0.03-3.9%N).
      Patients suffering from BRVO exhibited significantly higher intravitreal
      plasminogen (1.35 +/- 1.11%N) in comparison with controls (0.20 +/- 0.21%N, p <
      0.001). Intravitreal VEGF concentrations in the BRVO group (576 +/- 547 pg/ml)
      were significantly higher than these in controls (111 +/- 120 pg/ml, p = 0.003).
      There was a significant correlation between intravitreal functional plasminogen
      and intravitreal VEGF levels (r = 0.519, p = 0.003). CONCLUSIONS: Intravitreal
      functional plasminogen is significantly elevated in eyes suffering from BRVO and
      correlates with the extent of BRB breakdown. The induction of posterior vitreous
      detachment by using intravitreally administered recombinant tissue plasminogen
      activator (enzymatic vitreolysis) should be explored in further investigations.

PMID- 25059576
TI  - Up regulation of liver-enriched transcription factors HNF4a and HNF6 and liver
      specific microRNA (miR-122) by inhibition of let-7b in mesenchymal stem cells.
AB  - MicroRNAs are small non-coding RNAs that regulate key processes of the stem
      cells. Although, microRNAs have emerged as powerful regulators of
      differentiation, few studies have been focused on the post-transcriptional
      regulation of hepatic differentiation in mesenchymal stem cells (MSCs) by
      microRNAs. The aim of this study was to evaluate the specific effect of let-7
      microRNAs in particular let-7b in hepatic commitment of human adipose tissue
      derived mesenchymal stem cells (hAT-MSCs). The dynamic expression profile of let
      7a, b, c microRNAs and two liver-enriched transcription factors (LETFs) HNF4a and
      HNF6 was studied during in vitro hepatic differentiation of hAT-MSCs. Let-7b was
      used for transient overexpression and knockdown investigations. It was shown that
      the expression of LETFs is inversely correlated with those of let-7 miRNAs during
      differentiation progress (p < 0.05). Inhibition of let-7b caused upregulation of
      LETFs, an increase in the expression of miR-122 (p < 0.01) emulating the features
      of functional hepatocytes, and accumulation of hAT-MSCs in the G0 /G1 phase of
      cell cycle, triggering initiation of hepatic commitment. In conclusion, transient
      inhibition of let-7b activates hepatic differentiation of hAT-MSCs. The findings
      of this work might help optimization of in vitro hepatogenic differentiation
      utilizing microRNAs and hAT-MSCs that could be used for therapeutic purposes.

PMID- 25059577
TI  - Post-Traumatic Brain Injury: Genetic Susceptibility to Outcome.
AB  - It is estimated that 2% of the population from industrialized countries live with
      lifelong disabilities resulting from traumatic brain injury (TBI) and roughly one
      in four adults are unable to return to work 1 year after injury because of
      physical or mental disabilities. TBI is a significant public health issue that
      causes substantial physical and economical repercussions for the individual and
      society. Electronic databases (PubMed, Web of Science, Google Scholar) were
      searched with the keywords traumatic brain injury, TBI, genes and TBI, TBI
      outcome, head injury. Human studies on non-penetrating traumatic brain injuries
      reported in English were included. To provide health care workers with the basic
      information for clinical management we summarize and compare the data on post-TBI
      outcome with regard to the impact of genetic variation: apolipoprotein E (APOE),
      brain-derived neurotrophic factor (BDNF), calcium channel, voltage dependent P/Q
      type, catechol-O-methyltransferase (COMT), dopamine receptor D2 and ankyrin
      repeat and kinase domain containing 1 (DRD2 and ANKK1), interleukin-1 (IL-1),
      interleukin-6 (IL-6), kidney and brain expressed protein (KIBRA), neurofilament,
      heavy polypeptide (NEFH), endothelial nitric oxide synthase 3 (NOS3), poly (ADP
      ribose) polymerase-1 (PARP-1), protein phosphatase 3, catalytic subunit, gamma
      isozyme (PPP3CC), the serotonin transporter (5-HTT) gene solute carrier family 6
      member (SLC6A4) and tumor protein 53 (TP53). It is evident that contradicting
      results are attributable to the heterogeneity of studies, thus further researches
      are warranted to effectively assess a relation between genetic traits and
      clinical outcome following traumatic injuries. 

PMID- 25059578
TI  - The role of advocacy in the national strategy for maternal death review in
      Nigeria.
AB  - Strategic advocacy has played a substantial role in the development and
      implementation of maternal death review (MDR) in Nigeria. Stakeholders that
      include the Society of Gynaecology and Obstetrics of Nigeria have partnered with
      the Federal Ministry of Health to ensure a robust arrangement that will guarantee
      the success of MDR in this country. Consequently, it is envisaged that the
      program will both contribute to a sustainable reduction in the maternal mortality
      ratio and promote improvements in maternal health care. The Nigerian experience
      indicates that the influence of stakeholders, such as professional organizations,
      is essential to drive the development of MDR programs through provision of
      advocacy and technical support. The current convergence of factors-including
      global support, political will, technical innovations, and increased financial
      resources-provides an ideal opportunity to make MDR a reality for all countries. 

PMID- 25059579
TI  - Electrically controlled release of benzoic acid from poly(3,4
      ethylenedioxythiophene)/alginate matrix: effect of conductive poly(3,4
      ethylenedioxythiophene) morphology.
AB  - A drug-loaded conductive polymer/hydrogel blend, benzoic acid-loaded poly(3,4
      ethylenedioxythiophene/alginate (BA-loaded PEDOT/Alg) hydrogel, was used as a
      carrier/matrix for an electrical stimuli transdermal drug delivery system (TDDS).
      The effects of cross-linking ratio, PEDOT particle size, and electric field
      strength on the release mechanism and the diffusion coefficient (D) of BA were
      examined by using a modified Franz-diffusion cell. The diffusion scaling exponent
      value of BA is close to 0.5 which refers to the diffusion controlled mechanism,
      or the Fickian diffusion as the BA release mechanism. The D increased when there
      was a decrease in the cross-linking ratio due to the mesh size-hindering effect.
      When increasing electric field strength, the D of BA-loaded PEDOT/Alg hydrogel
      increased because the cathode-BA(-) electrorepulsion, electroinduced alginate
      expansion, and PEDOT electroneutralization simultaneously occurred. The highest D
      belonged to a blend with the smallest PEDOT particle and highest electrical
      conductivity. The D of BA was a function of the matrix mesh size except when drug
      size/mesh size was lower than 2.38 * 10(-3), where D of BA became mesh size
      independent as the matrix mesh size was extremely large. Thus, the fabricated
      conductive polymer hydrogel blends have a great potential to be used in TDDS
      under electrical stimulation. 

PMID- 25059580
TI  - Calcaneal fractures.

PMID- 25059581
TI  - Pachydermoperiostosis genetic screening in Lebanese families uncovers a novel
      SLCO2A1mutation.

PMID- 25059582
TI  - Depletion of Rictor, an essential protein component of mTORC2, decreases male
      lifespan.
AB  - Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR), robustly
      extends the lifespan of model organisms including mice. We recently found that
      chronic treatment with rapamycin not only inhibits mTOR complex 1 (mTORC1), the
      canonical target of rapamycin, but also inhibits mTOR complex 2 (mTORC2) in vivo.
      While genetic evidence strongly suggests that inhibition of mTORC1 is sufficient
      to promote longevity, the impact of mTORC2 inhibition on mammalian longevity has
      not been assessed. RICTOR is a protein component of mTORC2 that is essential for
      its activity. We examined three different mouse models of Rictor loss: mice
      heterozygous for Rictor, mice lacking hepatic Rictor, and mice in which Rictor
      was inducibly deleted throughout the body in adult animals. Surprisingly, we find
      that depletion of RICTOR significantly decreases male, but not female, lifespan.
      While the mechanism by which RICTOR loss impairs male survival remains obscure,
      we find that the effect of RICTOR depletion on lifespan is independent of the
      role of hepatic mTORC2 in promoting glucose tolerance. Our results suggest that
      inhibition of mTORC2 signaling is detrimental to males, which may explain in part
      why interventions that decrease mTOR signaling show greater efficacy in females. 

PMID- 25059583
TI  - Identification of initial severity determinants to predict arthritis after
      chikungunya infection in a cohort of French gendarmes.
AB  - BACKGROUND: The objective was to identify severity characteristics of initial
      chikungunya infection (CHIKV) stages associated with post-CHIKV arthritis and
      arthralgia. METHODS: French gendarmes exposed to the 2005-2006 CHIKV epidemic in
      Reunion Island who completed the 2006 (self-reporting acute and early chronic
      [median: 6 months] symptoms) and 2008 (Endpoint [median: 30 months]: self
      perceived recovery and rheumatic disorders (RDs)) surveys were included.
      Multinomial logistic regression and multiple correspondence analysis (MCA) were
      used. Arthralgia was defined by joint pain and/or stiffness and arthritis by
      joint swelling in addition to pain and/or stiffness. RESULTS: In 2008, 124
      (31.3%)/403 participants (101 CHIKV+/302 CHIKV-) reported arthralgia and 57
      (14.1%) arthritis. The multivariate model kept CHIKV infection, comorbidity and
      acute stage depressed mood as independent prognostic factors for both arthralgia
      and arthritis, but found early chronic stage RD as the main determinant of the
      same RD two years later.The MCA performed with the 85 CHIKV + patients who
      answered the question on self-perceived recovery enabled the calculation of
      severity scores based on initial symptoms that were strongly associated with
      persistent arthritis and, to a lesser extent, to arthralgia in bivariate
      analyses. The MCA graph clearly distinguished arthritis as the only RD associated
      with early severity indicators represented by sick leave, joint swelling and
      depressed mood during the acute stage, and early chronification of arthritis and
      depressed mood. CONCLUSION: Initial CHIKV severity predicted recovery, with
      higher severity associated with arthritis and lower severity with arthralgia.
      More interestingly, specific markers of post-CHIKV arthritis, which can easily be
      used by clinicians for case management, were identified.

PMID- 25059585
TI  - Home ventilation therapy in obstructive sleep apnea-hypopnea syndrome.
AB  - Obstructive sleep apnea-hypopnea is a highly prevalent disease that is often
      underdiagnosed at present. It has a significant economic and social welfare
      impact, accounting for a large part of the resources assigned to home respiratory
      therapies. As part of the 2014 SEPAR Year of the Chronic Patient and Domiciliary
      Respiratory Care sponsored by the Spanish Society of Pulmonology and Thoracic
      Surgery, this article reviews the most recent publications on the indications and
      controversial issues in the treatment of sleep apnea, the latest evidence for
      indication of various positive pressure devices, and adjustment modes, ranging
      from the use of empirical formulae or mathematical estimations to modern auto
      CPAP equipment, while not forgetting the gold standard of manual titration.
      Emphasis is placed on the need for monitoring required by patients to ensure
      treatment adherence and compliance. Finally, other therapies that are not the
      object of this article are briefly reviewed. 

PMID- 25059586
TI  - Torsion of Middle Lobe after Lobectomy. Correlation between Optical Bronchoscopy
      Computed Tomography Virtual Bronchoscopy.

PMID- 25059584
TI  - A thaumatin-like protein, Rj4, controls nodule symbiotic specificity in soybean.
AB  - Soybeans exhibit a nitrogen-fixing symbiosis with soil bacteria of the genera
      Bradyrhizobium and Ensifer/Sinorhizobium in a unique organ, the root nodule. It
      is well known that nodulation of soybean is controlled by several host genes
      referred to as Rj (rj) genes. Among these genes, a dominant allele, Rj4,
      restricts nodulation with specific bacterial strains such as B. elkanii USDA61
      and B. japonicum Is-34. These incompatible strains fail to invade the host
      epidermal cells as revealed by observations using DsRed-labeled bacteria. Here,
      we describe the molecular identification of the Rj4 gene by using map-based
      cloning with several mapping populations. The Rj4 gene encoded a thaumatin-like
      protein (TLP) that belongs to pathogenesis-related (PR) protein family 5. In
      rj4/rj4 genotype soybeans and wild soybeans, we found six missense mutations and
      two consecutive amino acid deletions in the rj4 gene as compared with the Rj4
      allele. We also found, using hairy root transformation, that the rj4/rj4 genotype
      soybeans were fully complemented by the expression of the Rj4 gene. Whereas the
      expression of many TLPs and other PR proteins is induced by biotic/abiotic
      stress, Rj4 gene expression appears to be constitutive in roots including root
      nodules. 

PMID- 25059587
TI  - Diagnosis and treatment of malignant pleural mesothelioma.
AB  - There are three major challenges in the diagnosis of malignant pleural
      mesothelioma: mesothelioma must be distinguished from benign mesothelial
      hyperplasia; malignant mesothelioma (and its subtypes) must be distinguished from
      metastatic carcinoma; and invasion of structures adjacent to the pleura must be
      demonstrated. The basis for clarifying the first two aspects is determination of
      a panel of monoclonal antibodies with appropriate immunohistochemical evaluation
      performed by highly qualified experts. Clarification of the third aspect requires
      sufficiently abundant, deep biopsy material, for which thoracoscopy is the
      technique of choice. Video-assisted needle biopsy with real-time imaging can be
      of great assistance when there is diffuse nodal thickening and scant or absent
      effusion. Given the difficulties of reaching an early diagnosis, cure is not
      generally achieved with radical surgery (pleuropneumonectomy), so liberation of
      the tumor mass with pleurectomy/decortication combined with chemo- or radiation
      therapy (multimodal treatment) has been gaining followers in recent years. In
      cases in which surgery is not feasible, chemotherapy (a combination of pemetrexed
      and platinum-derived compounds, in most cases) with pleurodesis or a tunneled
      pleural drainage catheter, if control of pleural effusion is required, can be
      considered. Radiation therapy is reserved for treatment of pain associated with
      infiltration of the chest wall or any other neighboring structure. In any case,
      comprehensive support treatment for pain control in specialist units is
      essential: this acquires particular significance in this type of malignancy. 

PMID- 25059588
TI  - Talking about Endobronchial Lipoma.

PMID- 25059589
TI  - [Complications of diabetes mellitus in the USA: improved results].

PMID- 25059590
TI  - Editorial comment.

PMID- 25059593
TI  - Association between postoperative pelvic anatomic features on magnetic resonance
      imaging and lower tract urinary symptoms after radical prostatectomy.
AB  - OBJECTIVE: To elucidate the etiology of lower urinary tract symptoms (LUTS) after
      radical prostatectomy, the present study investigated associations between
      postoperative urethral and vesical anatomic features on magnetic resonance
      imaging (MRI) and LUTS. PATIENTS AND METHODS: Fifty consecutive patients
      undergoing radical prostatectomy also underwent preoperative and postoperative
      MRI. Preoperative MRI only evaluated preoperative membranous urethral length
      (MUL). Postoperative MRI evaluated postoperative MUL, posterior-urethral vesical
      angle, depth of the urethrovesical junction (UVJ), and urinary pooling inside the
      urethra and bladder neck configuration. At the same time as postoperative MRI,
      International Prostate Symptom Score (IPSS), quality of life index, continence
      grade, and uroflowmetry parameters were investigated. Associations between
      preoperative or postoperative MRI variables and questionnaire results or
      uroflowmetry were analyzed to examine the relationships between the morphology of
      urethral and vesical anatomic features and LUTS. RESULTS: Preoperative and
      postoperative MRI variables were not significantly associated with IPSS total
      score or uroflowmetry results. Urinary pooling inside the urethra was
      significantly associated with urgency score in the IPSS (P = .005). Postoperative
      MUL (P <.001), depth of the UVJ (P = .002), and urinary pooling inside the
      urethra (P = .04) were significantly associated with continence grade.
      CONCLUSION: Urinary pooling inside the urethra might induce urgency, and
      postoperative MUL and depth of UVJ were related to urinary incontinence. Avoiding
      damage to the nerves involved in continence to prevent inflow of urine into the
      urethra, preservation of MUL, and development of procedures to prevent descent of
      the bladder neck during surgery are therefore recommended.

PMID- 25059592
TI  - Factors associated with continuing medical therapy after transurethral resection
      of prostate.
AB  - OBJECTIVE: To report the clinical characteristics of patients who have persistent
      lower urinary tract symptoms (LUTS) after surgery for benign prostatic
      hyperplasia (BPH) and continue their medical therapy postoperatively. MATERIALS
      AND METHODS: We retrospectively studied 372 patients who underwent transurethral
      resection of prostate for LUTS/BPH in 8 institutions to determine the differences
      between patients who continued LUTS/BPH medications for >3 months after surgery
      and those who did not. Preoperative, intraoperative, and postoperative clinical
      parameters were assessed. The Student t test and chi square test were used to
      compare each parameter between patient groups. Multivariate logistic regression
      analysis was performed to identify risk factors for persistent LUTS and
      continuing medical therapy after surgery. RESULTS: There were 205 patients
      (55.1%) who continued their LUTS/BPH medications for >3 months postoperatively.
      They reported poorer International Prostate Symptom Scores and uroflowmetry
      results after surgery. Multivariate analysis showed that age >70 years (odds
      ratio [OR], 2.474; P = .001), history of diabetes (OR, 1.949; P = .040), history
      of cerebrovascular accident (OR, 5.932; P = .001), any previous LUTS/BPH
      medication use (OR, 5.384; P = <0.001), and previous antimuscarinic drug use (OR,
      2.962; P = .016) were significantly associated with symptom persistency and
      continuing medical therapy. CONCLUSION: Many patients have persistent voiding
      dysfunction after surgical treatment for LUTS/BPH. Older age, history of
      diabetes, history of cerebrovascular accidents, and preoperative antimuscarinic
      drug uses are possible risk factors.

PMID- 25059594
TI  - The number of cores at first biopsy may suggest the need for a confirmatory
      biopsy in patients eligible for active surveillance-implication for clinical
      decision making in the real-life setting.
AB  - OBJECTIVE: To assess whether the number of cores at first prostate biopsy affect
      pathologic findings at radical prostatectomy (RP) in potential candidates for
      active surveillance (AS). MATERIAL AND METHODS: Two hundred seventy-five patients
      fulfilling Prostate Cancer Research International: Active Surveillance criteria
      (prostate-specific antigen level <= 10 ng/mL, prostate-specific antigen density
      <0.2 ng/mL/cm(3), number of positive cores <= 2, T1c-T2 clinical stage, Gleason
      score [GS] <= 6) underwent RP between 2005 and 2013 at a single institution.
      Patients were stratified into 3 groups according to different biopsy schemes (<=
      12 vs 13-18 vs >= 19 cores). Rates of pathologically confirmed insignificant
      prostate cancer (pIPCa; defined as RP GS <= 6, tumor volume <= 0.5 mL, and organ
      confined disease) and unfavorable disease (UD, defined as non-organ-confined
      disease and/or pathologic GS >= 7) at RP were stratified according to the biopsy
      schemes. Logistic regression analyses tested the effect of preoperative variables
      in predicting pIPCa and UD at RP. RESULTS: Of all, 23.3% and 33.4% patients
      harbored pIPCa and UD, respectively. pIPCa and UD were found in 15.7%, 32.1%,
      25.3% (P = .04) and in 48.1%, 23.8%, 24.1% (P <.001) patients with <= 12, 13-18,
      >= 19 cores, respectively. At multivariate analyses, number of biopsy cores
      emerged as an independent predictor of both pIPCa (<= 12 vs 13-18 cores: odds
      ratio [OR] = 2.34; P = .02) and UD (<= 12 vs 13-18 cores: OR = 0.39; P <.01; <=
      12 vs >= 19 cores: OR = 0.38; P <.01). CONCLUSION: Among candidates for AS,
      number of biopsy cores emerged as an independent predictor of pIPCa and UD at RP.
      These findings would suggest that the extent of initial biopsy sampling should be
      considered when addressing patients to AS and before planning any surveillance
      strategies.

PMID- 25059595
TI  - Large accumulation of micro-sized synthetic polymer particles in the sea surface
      microlayer.
AB  - Determining the exact abundance of microplastics on the sea surface can be
      susceptible to the sampling method used. The sea surface microlayer (SML) can
      accumulate light plastic particles, but this has not yet been sampled. The
      abundance of microplastics in the SML was evaluated off the southern coast of
      Korea. The SML sampling method was then compared to bulk surface water filtering,
      a hand net (50 MUm mesh), and a Manta trawl net (330 MUm mesh). The mean
      abundances were in the order of SML water > hand net > bulk water > Manta trawl
      net. Fourier transform infrared spectroscopy (FTIR) identified that alkyds and
      poly(acrylate/styrene) accounted for 81 and 11%, respectively, of the total
      polymer content of the SML samples. These polymers originated from paints and the
      fiber-reinforced plastic (FRP) matrix used on ships. Synthetic polymers from ship
      coatings should be considered to be a source of microplastics. Selecting a
      suitable sampling method is crucial for evaluating microplastic pollution. 

PMID- 25059596
TI  - Comparative mapping in the Poaceae family reveals translocations in the complex
      polyploid genome of sugarcane.
AB  - BACKGROUND: The understanding of sugarcane genetics has lagged behind that of
      other members of the Poaceae family such as wheat, rice, barley and sorghum
      mainly due to the complexity, size and polyploidization of the genome. We have
      used the genetic map of a sugarcane cultivar to generate a consensus genetic map
      to increase genome coverage for comparison to the sorghum genome. We have
      utilized the recently developed sugarcane DArT array to increase the marker
      density within the genetic map. The sequence of these DArT markers plus SNP and
      EST-SSR markers was then used to form a bridge to the sorghum genomic sequence by
      BLAST alignment to start to unravel the complex genomic architecture of
      sugarcane. RESULTS: Comparative mapping revealed that certain sugarcane
      chromosomes show greater levels of synteny to sorghum than others. On a
      macrosyntenic level a good collinearity was observed between sugarcane and
      sorghum for 4 of the 8 homology groups (HGs). These 4 HGs were syntenic to four
      sorghum chromosomes with from 98% to 100% of these chromosomes covered by these
      linked markers. Four major chromosome rearrangements were identified between the
      other four sugarcane HGs and sorghum, two of which were condensations of
      chromosomes reducing the basic chromosome number of sugarcane from x = 10 to x =
      8. This macro level of synteny was transferred to other members within the
      Poaceae family such as maize to uncover the important evolutionary relationships
      that exist between sugarcane and these species. CONCLUSIONS: Comparative mapping
      of sugarcane to the sorghum genome has revealed new information on the genome
      structure of sugarcane which will help guide identification of important genes
      for use in sugarcane breeding. Furthermore of the four major chromosome
      rearrangements identified in this study, three were common to maize providing
      some evidence that chromosome reduction from a common paleo-ancestor of both
      maize and sugarcane was driven by the same translocation events seen in both
      species.

PMID- 25059597
TI  - Limited evidence for the use of imaging to detect prostate cancer: a systematic
      review.
AB  - OBJECTIVE: To assess the diagnostic accuracy of imaging technologies for
      detecting prostate cancer in patients with elevated PSA-values or suspected
      findings on clinical examination. METHODS: The databases Medline, EMBASE,
      Cochrane, CRD HTA/DARE/NHS EED and EconLit were searched until June 2013. Pre
      determined inclusion criteria were used to select full text articles. Risk of
      bias in individual studies was rated according to QUADAS or AMSTAR. Abstracts and
      full text articles were assessed independently by two reviewers. The performance
      of diagnostic imaging was compared with systematic biopsies (reference standard)
      and sensitivity and specificity were calculated. RESULTS: The literature search
      yielded 5141 abstracts, which were reviewed by two independent reviewers. Of
      these 4852 were excluded since they did not meet the inclusion criteria. 288
      articles were reviewed in full text for quality assessment. Six studies, three
      using MRI and three using transrectal ultrasound were included. All were rated as
      high risk of bias. Relevant studies on PET/CT were not identified. CONCLUSION:
      Despite clinical use, there is insufficient evidence regarding the accuracy of
      imaging technologies for detecting cancer in patients with suspected prostate
      cancer using TRUS guided systematic biopsies as reference standard.

PMID- 25059598
TI  - Evaluation of a 32-channel versus a 12-channel head coil for high-resolution post
      contrast MRI in giant cell arteritis (GCA) at 3T.
AB  - The aim of this study was to evaluate the diagnostic value of a 32-channel head
      coil for the characterization of mural inflammation patterns in the superficial
      cranial arteries in patients with giant cell arteritis (GCA) compared to a
      standard 12-channel coil at 3T MRI. 55 patients with suspected GCA underwent high
      resolution T1-weighted post-contrast MRI at 3T to detect inflammation related
      vessel wall enhancement using both coils. To account for different time delays
      between contrast agent injection and sequence acquisition, the patients were
      divided into two cohorts: 27 patients were examined with the 32-channel coil
      first and 28 patients with the 12-channel coil first. Images were evaluated by
      two blinded readers with regard to image quality, artifact level and arteries'
      inflammation according to a standardized ranking scale; furthermore signal-to
      noise ratio (SNR) measurements were performed at three locations. Identification
      of arteries' inflammation was achieved with both coils with excellent inter
      observer agreement (kappa=0.89 for 12-channel and kappa=0.96 for 32-channel
      coil). Regarding image grading, the inter-observer variability was moderate for
      the 12-channel (kappa=0.5) and substantial for the 32-channel coil (kappa=0.63).
      Significantly higher SNR and improved image quality (p<0.01) were obtained with
      the 32-channel coil in either coil order. Image quality for depiction of the
      superficial cranial arteries was superior for the 32-channel coil. For
      standardized GCA diagnosis, the 12-channel coil was sufficient. 

PMID- 25059599
TI  - Hepatic artery stent-grafts for the emergency treatment of acute bleeding.
AB  - PURPOSE: We evaluated the technical success and clinical efficacy of stent-graft
      implantation for the emergency management of acute hepatic artery bleeding.
      METHODS: Between January 2010 and July 2013, 24 patients with hemorrhage from the
      hepatic artery were scheduled for emergency implantation of balloon expandable
      stent-grafts. The primary study endpoints were technical and clinical success,
      which were defined as successful stent-graft implantation with sealing of the
      bleeding site at the end of the procedure, and cessation of clinical signs of
      hemorrhage. The secondary study endpoints were complications during the procedure
      or at follow-up and 30-day mortality rate. RESULTS: In 23 patients, hemorrhage
      occurred after surgery, and in one patient hemorrhage occurred after trauma.
      Eight patients had sentinel bleeding. In most patients (n=16), one stent-graft
      was implanted. In six patients, two overlapping stent-grafts were implanted. The
      stent-grafts had a target diameter between 4mm and 7 mm. Overall technical
      success was 88%. The bleeding ceased after stent-graft implantation in 21
      patients (88%). The mean follow-up was 137 +/- 383 days. In two patients, re
      bleeding from the hepatic artery occurred during follow-up after 4 and 29 days,
      respectively, which could be successfully treated by endovascular therapy. The
      complication rate was 21% (minor complication rate 4%, major complication rate
      17%). The 30-day mortality rate was 21%. CONCLUSIONS: Implantation of stent
      grafts in the hepatic artery is an effective emergency therapy and has a good
      technical success rate for patients with acute arterial hemorrhage.

PMID- 25059600
TI  - Fifteen years of Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC).
AB  - Here I describe the history of the Stable Isotope Labeling by Amino Acids in Cell
      culture (SILAC) technology. Although published in 2002, it had already been
      developed and used in my laboratory for a number of years. From the beginning, it
      was applied to challenging problems in cell signaling that were considered out of
      reach for proteomics at the time. It was also used to pioneer proteomic
      interactomics, time series and dynamic posttranslational modification studies.
      While initially developed for metabolically accessible systems, such as cell
      lines, it was subsequently extended to whole animal labeling as well as to
      clinical applications-in the form or spike-in or super-SILAC. New formats and
      applications for SILAC labeling continue to be developed, for instance for
      protein-turnover studies.

PMID- 25059601
TI  - Stable isotope labeling by amino acids applied to bacterial cell culture.
AB  - Stable isotope labeling by amino acids in cell culture (SILAC) is a widely used
      approach in quantitative proteomics; however, due to limitations such as required
      auxotrophy for the amino acids employed for labeling, it was thus far rarely
      employed in bacteria. Although limitations of SILAC in microbiological
      applications are significant and restrict its use exclusively to cells cultured
      in minimal media, we and others have successfully used it to fully label
      proteomes of model bacteria and measure their relative expression dynamics under
      different experimental conditions. Here we provide a brief overview of
      applications of SILAC in bacteria and describe a detailed protocol for SILAC
      labeling of Escherichia coli and Bacillus subtilis cells in culture, which in
      many cases can be applied to other members of both gram-positive and gram
      negative bacterial species. 

PMID- 25059602
TI  - SILAC labeling of yeast for the study of membrane protein complexes.
AB  - Despite their simplicity compared to multicellular organisms, single-celled
      yeasts such as the baker's yeast Saccharomyces cerevisiae are widely recognized
      as model organisms for the study of eukaryotic cell biology. To gain deeper
      insights into the molecular mechanisms underlying cellular processes, it is of
      utmost interest to establish the interactome of distinct proteins and to
      thoroughly analyze the composition of individual protein complexes and their
      dynamics. Combining affinity purification of epitope-tagged proteins with high
      resolution mass spectrometry and quantitative proteomics strategies, in
      particular stable isotope labeling by amino acids in cell culture (SILAC),
      represents an unbiased and powerful approach for a most accurate characterization
      of protein complexes. In this chapter, we provide detailed protocols for the
      generation of yeast strains (S. cerevisiae) amenable to SILAC-labeling, for
      epitope tagging of a protein of interest for affinity purification, and for the
      SILAC-based characterization of membrane protein complexes including the
      identification of stable core components and transient interaction partners. 

PMID- 25059603
TI  - Whole proteome analysis of the protozoan parasite Trypanosoma brucei using stable
      isotope labeling by amino acids in cell culture and mass spectrometry.
AB  - The single-celled protozoan Trypanosoma brucei spp. is the causative agent of
      human African trypanosomiasis and nagana in cattle. Quantitative proteomics for
      the first time has allowed for the characterization of the proteome from several
      different life stages of the parasite (Butter et al., Mol Cell Proteomics 12:172
      179, 2013; Gunasekera et al., BMC Genomics 13:556, 2012; Urbaniak et al., PloS
      One 7(5):e36619, 2012). To achieve this, stable isotope labeling by amino acids
      in cell culture (SILAC) (Ong et al., Mol Cell Proteomics 1:376-386, 2002) was
      adapted to T. brucei spp. cultures. T. brucei cells grown in standard media with
      dialyzed fetal calf serum containing heavy isotope-labeled amino acids (arginine
      and lysine) show efficient incorporation of the labeled amino acids into the
      whole cell proteome (8-12 divisions) and no detectable amino acid conversions.
      The method can be applied to both of the major life stages of the parasite and in
      combination with RNAi or gene knockout approaches.

PMID- 25059604
TI  - Stable isotope labeling by amino acids in cultured primary neurons.
AB  - Cultured primary neurons are a well-established model for the study of neuronal
      function. Conventional stable isotope labeling with amino acids in cell culture
      (SILAC) requires nearly complete metabolic labeling of proteins and therefore is
      difficult to apply to cultured primary neurons, which do not divide in culture.
      Here we describe a protocol that utilizes a multiplex SILAC labeling strategy for
      primary cultured neurons. In this strategy, two different sets of heavy amino
      acids are used for labeling cells for the different experimental conditions. This
      allows for a straightforward SILAC quantitation using partially labeled cells
      because the two cell populations are always equally labeled. 

PMID- 25059605
TI  - SILAC and alternatives in studying cellular proteomes of plants.
AB  - Quantitative proteomics by metabolic labeling has a high impact on the growing
      field of plant systems biology. SILAC has been pioneered and optimized for plant
      cell culture systems allowing for SILAC-based quantitative experiments in
      specialized experimental setups. In comparison to other model organisms, the
      application of SILAC to whole plants is challenging. As autotrophic organisms,
      plants under their natural growth conditions can hardly be fully labeled with
      stable isotope-coded amino acids. The metabolic labeling with inorganic nitrogen
      is therefore the method of choice for most whole-plant physiological questions.
      Plants can easily metabolize different inorganic nitrogen isotopes. The
      incorporation of the labeled inorganic nitrogen then results in proteins and
      metabolites with distinct molecular mass, which can be detected on a mass
      spectrometer. In comparative quantitative experiments, similarly as in SILAC
      experiments, treated and untreated samples are differentially labeled by nitrogen
      isotopes and jointly processed, thereby minimizing sample-to-sample variation. In
      recent years, heavy nitrogen labeling has become a widely used strategy in
      quantitative proteomics and novel approaches were developed for metabolite
      identification. Here we present a typical hydroponics setup, the workflow for
      processing of samples, mass spectrometry and data analysis for large-scale
      metabolic labeling experiments of whole plants.

PMID- 25059606
TI  - In vivo stable isotope labeling by amino acids in Drosophila melanogaster.
AB  - The fruit fly Drosophila melanogaster is one of the most widely used and well
      studied model organisms in biology and therefore a promising tool for
      quantitative proteomics. Here, we describe a method to label D. melanogaster with
      stable isotope labeled amino acids in vivo. Feeding flies with heavy lysine
      labeled yeast cells leads to virtually complete heavy labeling already in the
      first filial generation. The approach is simple, fast, and cost-effective, which
      makes SILAC flies an attractive model system for the emerging field of in vivo
      quantitative proteomics. 

PMID- 25059607
TI  - Stable isotope labeling for proteomic analysis of tissues in mouse.
AB  - Since the first metabolic labeling experiments with stable isotopes beginning of
      the last century, several approaches were pursued to monitor protein dynamics in
      living animals. Today, almost all model organisms from bacteria to rodents can be
      fully labeled with SILAC (stable isotope labeling of amino acids in cell culture)
      amino acids. The development of special media and diets containing the labeled
      amino acids provides an efficient way to metabolically label prokaryotic and
      eukaryotic organisms. Preferentially, the essential amino acid lysine ((13)C6
      lysine) is used to label mice (Mus musculus) and after one generation the natural
      isotope is fully replaced by the stable (13)C6-lysine isotope. So far, the SILAC
      mouse approach has been used to analyze several transgenic and knockout mouse
      models. Spike-in of labeled proteins into non-labeled samples provides an
      accurate relative protein quantification method without any chemical
      modification. Here we describe how to establish a SILAC mouse colony and describe
      the analysis of skeletal muscle tissue with different metabolic and contractile
      profiles. 

PMID- 25059608
TI  - Identification of novel protein functions and signaling mechanisms by genetics
      and quantitative phosphoproteomics in Caenorhabditis elegans.
AB  - Stable isotope labeling by amino acids combined with mass spectrometry is a
      widely used methodology for measuring relative changes in protein and
      phosphorylation levels at a global level. We have applied this method to the
      model organism Caenorhabditis elegans in combination with RNAi-mediated gene
      knockdown by feeding the nematode on pre-labeled lysine auxotroph Escherichia
      coli. In this chapter, we describe in details the generation of the E. coli
      strain, incorporation of heavy isotope-labeled lysine in C. elegans, and the
      procedure for a comprehensive global phosphoproteomic experiment. 

PMID- 25059609
TI  - SILAC-based temporal phosphoproteomics.
AB  - In recent years, thanks to advances in Mass Spectrometry (MS)-based quantitative
      proteomics, studies on signaling pathways have moved from a detailed description
      of individual components to system-wide analysis of entire signaling cascades,
      also providing spatio-temporal views of intracellular pathways. Quantitative
      proteomics that combines stable isotope labeling by amino acid in cell culture
      (SILAC) with enrichment strategies for post-translational modification-bearing
      peptides and high-performance tandem mass spectrometry represents a powerful and
      unbiased approach to monitor dynamic signaling events. Here we provide an
      optimized SILAC-based proteomic workflow to analyze temporal changes in
      phosphoproteomes, which involve a generic three step enrichment protocol for
      phosphopeptides. SILAC-labeled peptides from digested whole cell lysates are as a
      first step enriched for phosphorylated tyrosines by immunoaffinity and then
      further enriched for phosphorylated serine/threonine peptides by strong cation
      exchange in combination with titanium dioxide-beads chromatography. Analysis of
      enriched peptides on Orbitrap-based MS results in comprehensive and accurate
      reconstruction of temporal changes of signaling networks. 

PMID- 25059610
TI  - Global ubiquitination analysis by SILAC in mammalian cells.
AB  - Ubiquitination is a versatile and dynamic posttranslational modification in
      cells, regulating almost all cellular events. With rapid developments of affinity
      capture reagents and high-resolution mass spectrometry, it is now feasible to
      globally analyze the ubiquitinated proteome (ubiquitome) using quantitative
      strategies, such as stable isotope labeling with amino acids in cell culture
      (SILAC). Here we describe in detail a SILAC protocol to profile the ubiquitome in
      mammalian cells including protein labeling, antibody-based enrichment, and
      analysis by mass spectrometry. 

PMID- 25059611
TI  - Quantifying in vivo, site-specific changes in protein methylation with SILAC.
AB  - Interest in protein methylation has grown rapidly in recent years. Mass
      spectrometry-based proteomics is ideally suited to characterize protein
      modifications, but the multiplicity of methylated residues and the lack of
      efficient methods to enrich methylated proteins have limited the proteomic
      identification of protein methylation sites. In this protocol, we compare two
      metabolic labeling approaches, stable isotope labeling by amino acids in cell
      culture (SILAC) and its variant heavy methyl SILAC, for studying protein
      methylation. Instead of heavy lysine and arginine in the typical SILAC
      experiment, heavy methyl SILAC uses (13)C, (2)H methionine as the labeling amino
      acid. As cells convert methionine to S-adenosylmethionine, heavy methyl SILAC
      encodes a 4 Da mass tag for each methyl group, distinguishing between degrees of
      methylation is possible from mass difference alone. We provide a protocol for
      SILAC-based analyses of protein methylation and highlight the strengths and
      weaknesses of each method for targeted and proteomic analyses. 

PMID- 25059612
TI  - Applying SILAC for the differential analysis of protein complexes.
AB  - Pull-downs based on tag fusion proteins as well as immunoprecipitations (IP) are
      widely used methods to analyze protein interactions. Selectivity and specificity
      of both methods are compromised by nonspecific binding to the capture agent or
      carrier beads thereby generating false positives. Here, we provide a method
      combining stable isotope labeling of amino acids in cell culture (SILAC) with
      affinity purification, coupled to quantitative tandem mass spectrometry. It
      permits the analysis of protein interactions with high sensitivity, while being
      able to discriminate contaminants and nonspecific binders. Besides pruning out
      contaminants, high-resolution MS data combined with quantitative proteomics
      software allow the comparative analysis of protein interaction patterns of
      different protein variants, for example mutated versus normal protein variant or
      of regulatory changes in a given protein complex due to different states of
      activity. 

PMID- 25059613
TI  - Defining dynamic protein interactions using SILAC-based quantitative mass
      spectrometry.
AB  - Protein-protein interactions are essential to various physiological processes in
      living cells. A full characterization of protein interactions is critical to our
      understanding of their roles in the regulation of protein functions. Affinity
      purification coupled with mass spectrometry (AP-MS) has become one of the most
      effective approaches to systematically study protein-protein interactions. In
      combination with quantitative mass spectrometry, specific interacting proteins
      can be efficiently distinguished from nonspecific background proteins. Based on
      interaction affinity and kinetics, protein interactions can be classified into
      different categories such as stable and dynamic interactions. Standard
      biochemical methods are effective in capturing and identifying stable protein
      interactions but are not sufficient enough to identify dynamic interactors. In
      this chapter, we describe integrated strategies to allow the identification of
      dynamic interactors of protein complexes by incorporating new sample preparation
      methods with SILAC-based quantitation. 

PMID- 25059614
TI  - Identifying nuclear protein-protein interactions using GFP affinity purification
      and SILAC-based quantitative mass spectrometry.
AB  - Many cellular proteins assemble into macromolecular protein complexes. Therefore,
      identifying protein-protein interactions (PPIs) is essential to gain insight into
      the function of proteins. Recently established quantitative mass spectrometry
      based techniques have significantly improved the unbiased search for PPIs. In
      this chapter, we describe a single-step GFP affinity purification method combined
      with SILAC-based quantitative mass spectrometry that can be used to identify
      nuclear PPIs in mammalian cells. 

PMID- 25059615
TI  - Analyzing the protein assembly and dynamics of the human spliceosome with SILAC.
AB  - Quantitative mass spectrometry has become an indispensable tool in proteomic
      studies. Numerous methods are available and can be applied to approach different
      issues. In most studies these issues include the quantitative comparison of
      different cell states, the identification of specific interaction partners or
      determining degrees of posttranslational modification. In this chapter we
      describe a SILAC-based quantification in order to analyze dynamic protein changes
      during the assembly of the human spliceosome on a pre-mRNA in vitro. We provide
      protocols for assembly of spliceosomes on pre-mRNA (including generation of pre
      mRNAs and preparation of nuclear extracts), quantitative mass spectrometry (SILAC
      labeling, sample preparation), and data analysis to generate timelines for the
      dynamic protein assembly. 

PMID- 25059616
TI  - Identification and validation of protein-protein interactions by combining co
      immunoprecipitation, antigen competition, and stable isotope labeling.
AB  - Co-immunoprecipitation (coIP) in combination with mass spectrometry (MS) is a
      powerful tool to identify potential protein-protein interactions. However,
      unspecifically precipitated proteins usually result in large numbers of false
      positive identifications. Here we describe a detailed protocol particularly
      useful in plant sciences that is based on (15)N stable isotope labeling of cells,
      (14)N antigen titration, and coIP/MS to distinguish true from false protein
      protein interactions. 

PMID- 25059617
TI  - Protein correlation profiling-SILAC to study protein-protein interactions.
AB  - An interactome describes the global organization of protein interactions within a
      cell and is typically generated using affinity purification-mass spectrometry (AP
      MS), yeast two-hybrid screening, or protein-fragment complementation assays
      (Gavin et al. Nature 440: 631-636, 2006; Krogan et al. Nature 440: 637-643, 2006;
      Uetz et al. Nature 403: 623-627, 2000; Tarassov et al. Science 320: 1465-1470,
      2008). These techniques have been widely used to depict the interactome as we
      know it today but current models of interactomes do not contain stoichiometric or
      temporal information. In this chapter we describe size-exclusion chromatography
      (SEC) combined with protein correlation profiling-stable isotope labeling by
      amino acids in cell culture (PCP-SILAC) to generate dynamic chromatographs for
      thousands of proteins (Kristensen et al. Nat Methods 9: 907-909, 2012). Using the
      precise co-elution of two proteins as evidence that they interact, it is possible
      to identify similar numbers of protein interactions without overexpression or
      creating fusion proteins as other high-throughput techniques require. In
      addition, triplex SILAC allows us to quantify protein stoichiometry and temporal
      changes to the interactome following perturbation. Finally, SEC-PCP-SILAC is very
      time efficient since it generates two orders of magnitude fewer samples for LC-MS
      analysis and avoids the tedious tagging and purification steps, making it
      possible for everyone with a single mass spectrometer to study the interactome.

PMID- 25059618
TI  - Autophagosomal proteome analysis by protein correlation profiling-SILAC.
AB  - Autophagy is one of the two major degradation pathways within eukaryotic cells.
      Nevertheless, little is known about the protein composition of autophagosomes,
      the vesicles shuttling proteins to lysosomes for degradation. Protein correlation
      profiling in combination with stable isotope labeling by amino acids in cell
      culture is a stringent method to investigate the dynamics of the autophagosomal
      proteome. It enables the discrimination between autophagosomal and co-purifying
      proteins identifying organellar candidate proteins for further investigation. 

PMID- 25059619
TI  - Design and application of super-SILAC for proteome quantification.
AB  - Stable isotope labeling with amino acids in cell culture (SILAC) is considered
      the most accurate method for proteome quantification by mass spectrometry. As it
      relies on active protein translation, it was traditionally limited to cells in
      culture and was not applicable to tissues. We have previously developed the super
      SILAC mix, which is a mixture of several cell lines that serves as an internal
      spike-in standard for the study of human tumor tissue. The super-SILAC mix
      greatly improves the quantification accuracy while lowering error rates, and it
      is a simple, economic, and robust technique. Here we describe the design and
      application of super-SILAC to a broad range of biological systems, for basic
      biological research as well as clinical one. 

PMID- 25059620
TI  - Proteomics meets genetics: SILAC labeling of Drosophila melanogaster larvae and
      cells for in vivo functional studies.
AB  - Stable isotope labeling by amino acids in cell culture (SILAC) is an established
      and potent method for quantitative proteomics. When combined with high-resolution
      mass spectrometry (MS) and efficient algorithms for the analysis of quantitative
      MS data, SILAC has proven to be the strategy of choice for the in-depth
      characterization of functional states at the protein level. The fruit fly
      Drosophila melanogaster is one of the most widely used model systems for studies
      of genetics and developmental biology. Despite this, a global proteomic approach
      in Drosophila is rarely considered. Here, we describe an adaptation of SILAC for
      functional investigation of fruit flies by proteomics: We illustrate how to
      perform efficient SILAC labeling of cells in culture and whole fly larvae. The
      combination of SILAC, a highly accurate global protein quantification method, and
      of the fruit fly, the prime genetics and developmental model, represents a unique
      opportunity for quantitative proteomic studies in vivo.

PMID- 25059621
TI  - Analysis of secreted proteins using SILAC.
AB  - Secreted proteins serve a crucial role in the communication between cells,
      tissues, and organs. Proteins released to the extracellular environment exert
      their function either locally or at distant points of the organism. Proteins are
      secreted in a highly dynamic fashion by cells and tissues in the body responding
      to the stimuli and requirements presented by the extracellular milieu.
      Characterization of secretomes derived from various cell types has been performed
      using different quantitative mass spectrometry-based proteomics strategies,
      several of them taking advantage of labeling with stable isotopes. Here, we
      describe the use of Stable Isotope Labeling by Amino acids in Cell culture
      (SILAC) for the quantitative analysis of the skeletal muscle secretome during
      myogenesis. 

PMID- 25059622
TI  - Identification of microRNA targets by pulsed SILAC.
AB  - Pulsed stable isotope labeling by amino acids in cell culture (pulsed SILAC or
      pSILAC) allows to monitor and quantify the de novo synthesis of proteins in an
      unbiased fashion on a proteome-wide scale. The high applicability of this
      metabolic labeling technique has been demonstrated for the identification of
      posttranscriptional changes in gene expression on the proteome level, in
      particular those caused by microRNAs. The application of pSILAC allows the
      selective quantification of newly synthesized proteins and thus the detection of
      differences in protein translation. This is of particular interest in the case of
      microRNA-mediated regulations, which characteristically cause rather modest
      decreases in protein amounts that may be difficult to detect by other proteomic
      methods. Here, we describe a detailed protocol for using pSILAC to track miRNA
      mediated changes in protein expression, using the p53-induced miR-34a microRNA as
      a prototypic example of microRNA-mediated regulations.

PMID- 25059623
TI  - MaxQuant for in-depth analysis of large SILAC datasets.
AB  - Proteomics experiments can generate very large volumes of data, in particular in
      situations where within one experimental design many samples are compared to each
      other, possibly in combination with pre-fractionation of samples prior to LC-MS
      analysis. Here we provide a step-by-step protocol explaining how the current
      MaxQuant version can be used to analyze large SILAC-labeling datasets in an
      efficient way.

PMID- 25059624
TI  - Apixaban and risk of myocardial infarction: meta-analysis of randomized
      controlled trials.
AB  - The coagulation system contributes greatly to the evolution of myocardial
      infarction (MI). Anticoagulation may reduce the occurrence of MI as monotherapy
      or with concomitant use of aspirin. Activated factor X antagonists (anti-Xa) and
      direct thrombin inhibitors have promising results in various indications in non
      inferiority trials. However, results regarding their cardiovascular safety are
      heterogeneous. We systematically evaluated the risk of MI and mortality in
      patients receiving the new-generation oral anti-Xa agent apixaban. Electronic
      databases were searched to find prospective, randomized, controlled clinical
      trials (RCT) that evaluated the clinical impact of apixaban. Efficacy measures
      included frequency of MI, cardiovascular and overall mortality. Outcome
      parameters of RCTs were pooled with a random-effects model. Between January 2000
      and December 2013, 12 RCTs comprising 54,054 patients were identified. Based on
      the pooled results, there was no increase in the risk of MI in patients treated
      with apixaban [odds ratio (OR) 0.90; 95 % confidence interval (CI) 0.77-1.05; p =
      0.17] compared to different controls. Cardiovascular and overall mortality with
      apixaban was comparable to the control groups (OR 0.88; 95 % CI 0.72-1.06; p =
      0.18, OR 0.89; 95 % CI 0.77-1.03; p = 0.11, respectively). The pooled risk of
      major bleeding was lower in the apixaban treated groups (OR 0.84; 95 % CI 0.62
      1.12; p = 0.23) however this reached significant level only in subgroup analysis
      of trials with anticoagulant regimes in the control (OR 0.66; 95 % CI 0.51-0.87;
      p = 0.003). In a broad spectrum of patients and compared to different controls
      apixaban treatment was not associated with an increase in MI or mortality.

PMID- 25059625
TI  - Assessment of image quality in real time three-dimensional dobutamine stress
      echocardiography: an integrated 2D/3D approach.
AB  - BACKGROUND: Three-dimensional (3D) stress echocardiography is a relatively new
      technique offering the potential to acquire images of the entire left ventricle
      from 1 or 2 transducer positions in a time-efficient manner. Relative to two
      dimensional (2D) imaging, the ability to quickly acquire full volume images
      during peak stress with 3D echocardiography can eliminate left ventricular (LV)
      foreshortening while reducing inter-operator variability. Our objectives were to
      (1) determine the practicality of a novel integrated 2D/3D stress protocol in
      incorporating 3D imaging into a standard 2D stress echocardiogram and (2) to
      determine whether the quality of imaging using the novel 2D/3D protocol was
      sufficient for interpretation. METHODS: Twenty-five patients referred for stress
      echocardiography underwent an integrated 2D/3D image acquisition protocol. LV
      segments were scored from 0 (absent or no clear endocardial visualization) to 3
      (excellent/full visualization of endocardial border) with each modality. 2D
      segment quality scoring was compared with 3D. An integrated score was compared
      with either 2D or 3D imaging alone. RESULTS: Two-dimensional and 3D imaging were
      optimal for differing segments and the integrated protocol was superior to either
      modality alone. 3D imaging was superior in visualizing the anterior and
      anterolateral region of the base segments, compared to 2D imaging. 3D imaging was
      less useful for the base, the mid-inferior, and the inferoseptal segments, thus
      emphasizing the need to retain 2D imaging in stress echocardiography at this
      time. CONCLUSION: The integrated 2D/3D protocol approach to stress
      echocardiography is technically feasible and maximizes image quality of
      dobutamine stress echocardiography, improving patient assessment.

PMID- 25059626
TI  - Surface landmark quantification of embryonic mouse craniofacial morphogenesis.
AB  - BACKGROUND: Morphometric quantification of subtle craniofacial variation in
      studies of experimentally modified embryonic mice has proved valuable in
      determining the effects of developmental perturbations on craniofacial
      morphogenesis. The direct comparison of landmark coordinate data from embryos of
      many different mouse strains and mouse models can advance our understanding of
      the bases for craniofacial variation. We propose a standard set of craniofacial
      surface landmarks, for use with embryonic day (E) 10.5-12.5 mice, to serve as the
      foundation for this type of data compilation and analysis. We quantify the intra-
      and inter-observer landmark placement variation associated with each landmark and
      determine how the results of a simple ontogenetic analysis might be influenced by
      selection of landmark set. RESULTS: Intraobserver landmark placement error for
      experienced landmarkers generally remains below 0.1 mm, with some landmarks
      exhibiting higher values at E11.5 and E12.5. Interobserver error tends to
      increase with embryonic age and those landmarks defined on wide inflections of
      curves or facial processes exhibit the highest error. Landmarks with highest
      intra- or inter-observer are identified and we determine that their removal from
      the dataset does not significantly change the vectors of craniofacial shape
      change associated with an ontogenetic regression. CONCLUSIONS: Our quantification
      of landmark placement error demonstrates that it is preferable for a single
      observer to identify all landmark coordinates within a single study and that
      significant training and experience are necessary before a landmarker can produce
      data for use in larger meta-analyses. However, we are confident that this
      standard landmark set, once landmarks with higher error are removed, can serve as
      a foundation for a comparative dataset of facial morphogenesis across various
      mouse populations to help identify the developmental bases for phenotypic
      variation in the craniofacial complex.

PMID- 25059627
TI  - Obituary: Kenneth Alan Bennett (October 3, 1935 - February 6, 2014).

PMID- 25059628
TI  - Dissecting the cyclic di-guanylate monophosphate signalling network regulating
      motility in Salmonella enterica serovar Typhimurium.
AB  - Flagella-mediated swimming and swarming motility in Salmonella enterica serovar
      Typhimurium is intercalated with the cyclic di-guanylate monophosphate (c-di-GMP)
      signalling network. In this study, we identified the GGDEF domain proteins
      STM2672, STM4551 and STM1987 as key di-guanylate cyclases involved in regulation
      of motility in a DeltayhjH phosphodiesterase gene deletion mutant with elevated c
      di-GMP levels inhibiting motility. Surprisingly, these di-guanylate cyclases
      distinctively inhibited motility through the c-di-GMP receptors YcgR and the
      cellulose synthase BcsA, whereby STM2672 corresponded to YcgR, STM1987 to BcsA
      and STM4551 to both receptors. Although downregulation of motility is believed to
      prepare the bacterial cells for surface adhesion and biofilm formation, the major
      biofilm regulator CsgD of S. sv. Typhimurium was not involved in the regulation
      of swimming or swarming motility. Together with previously identified c-di-GMP
      networks regulating flagella-related phenotypes, flagella biosynthesis is a major
      target of c-di-GMP signalling in S. sv. Typhimurium. 

PMID- 25059629
TI  - Point: the quest for clean competition in sports: are we the dopes?

PMID- 25059630
TI  - Counterpoint: the quest for clean competition in sports: deterrence and the role
      of detection.

PMID- 25059631
TI  - Does neoadjuvant treatment before oncologic esophagectomy affect the
      postoperative quality of life? A prospective, longitudinal outcome study.
AB  - To evaluate the cancer patients' quality of life (QoL) following esophagectomy
      the focus was placed on the impact of neoadjuvant treatment before surgery. For
      patients undergoing oncologic surgery, the QoL is generally accepted as an
      important outcome parameter in addition to clinical parameters. This prospective
      nonrandomized study evaluated QoL in patients treated by preoperative
      chemo(radio)therapy followed by either surgery or surgery alone with special
      focus on the postoperative course. QoL was assessed in 131 consecutive patients
      who underwent surgery for esophageal cancer. The EORTC-QLQ-C30 and a tumor
      specific module were administered before surgery, at discharge, 3, 6, 12, and 24
      months after surgery. Clinical data were collected prospectively and a follow up
      was performed every 6 months. The histological type of cancer was squamous cell
      carcinoma in 49.6% and adenocarcinoma in 50.4%. There was no significant
      difference between patients that were treated neoadjuvantly and those that were
      first operated on with regard to morbidity, mortality, and survival rates (5-year
      survival rate of 34%). Most QoL scores dropped significantly below the baseline
      in the early postoperative period and recovered slowly during the follow-up
      period to almost preoperative levels in many scores. There was no statistically
      significant difference in any of the QoL scales between neoadjuvantly treated or
      primary operated patients. Esophageal resections are associated with significant
      deterioration of QoL, which slowly recovers during the follow-up period to an
      almost preoperative level. Neoadjuvant treatment seems to not further negatively
      affect the QoL deterioration. 

PMID- 25059632
TI  - Urodynamic after-contraction waves: a large observational study in an adult
      female population and correlation with bladder and ureter emptying functions in
      women.
AB  - OBJECTIVE: To evaluate different patterns of after-contraction (A-C) waves
      detected during urodynamic evaluation in women. PATIENTS AND METHODS: 4,110 women
      were prospectively observed regarding the presence of A-C waves upon urodynamic
      evaluation. Intravenous pyelography and ultrasound were requested. Paired t test,
      chi(2) test, Wilcoxon's rank sum test and correlation analysis were performed
      with a 95% significance level. RESULTS: There were three distinguishing patterns
      of A-C: type I - detrusor contraction after the regular voiding phase, type II -
      detrusor contraction persisting after the flow rate had stopped, and type III -
      rebound of the detrusor contraction after the flow. A-C was observed in 13.9% of
      the women. Type I A-C wave patterns were present in 68 patients (11.8%), type II
      A-C wave patterns in 477 patients (83.2%), and type III A-C wave patterns in 28
      patients (10.3%). Studies with intravenous pyelography and ultrasound very
      frequently showed bladder mucosa, muscle thickening or trabeculation. Secondary
      ureterectasis related to A-C waves was also observed. Additionally, watts factor,
      maximum flow rate, detrusor pressure and opening detrusor pressure were markedly
      elevated in patients with type III A-C, suggesting enhanced detrusor contraction
      in these A-C waves. CONCLUSION: A-C waves are a real urodynamic entity with
      different patterns of presentation and with clinical and morphological
      alterations.

PMID- 25059633
TI  - Platelet lysate and granulocyte-colony stimulating factor serve safe and
      accelerated expansion of human bone marrow stromal cells for stroke therapy.
AB  - Autologous human bone marrow stromal cells (hBMSCs) should be expanded in the
      animal serum-free condition within clinically relevant periods in order to secure
      safe and effective cell therapy for ischemic stroke. This study was aimed to
      assess whether the hBMSCs enhance their proliferation capacity and provide
      beneficial effect in the infarct brain when cultured with platelet lysate (PL)
      and granulocyte-colony stimulating factor (G-CSF). The hBMSCs were cultured in
      the fetal calf serum (FCS)-, PL-, or PL/G-CSF-containing medium. Cell growth
      kinetics was analyzed. The hBMSCs-PL, hBMSC-PL/G-CSF, or vehicle was
      stereotactically transplanted into the ipsilateral striatum of the rats subjected
      to permanent middle cerebral artery occlusion 7 days after the insult. Motor
      function was assessed for 8 weeks, and the fate of transplanted hBMSCs was
      examined using immunohistochemistry. As the results, the hBMSCs-PL/G-CSF showed
      more enhanced proliferation than the hBMSCs-FCS and hBMSCs-PL. Transplantation of
      hBMSCs expanded with the PL- or PL/G-CSF-containing medium equally promoted
      functional recovery compared with the vehicle group. Histological analysis
      revealed that there were no significant differences in their migration, survival,
      and neural differentiation in the infarct brain between the hBMSCs-PL and hBMSCs
      PL/G-CSF. These findings strongly suggest that the combination of PL and G-CSF
      may accelerate hBMSC expansion and serve safe cell therapy for patients with
      ischemic stroke at clinically relevant timing. 

PMID- 25059634
TI  - Predictors for chronic pain-related health care utilization: a cross-sectional
      nationwide study in Iceland.
AB  - BACKGROUND: Individuals with chronic pain are among the most frequent users of
      health care. Still, a significant percentage does not utilize health care for
      pain. A range of factors predict chronic pain-related health care utilization.
      DESIGN: A cross-sectional study aimed at identifying predictors of chronic pain
      related health care utilization and comparing predictors between men and women.
      METHODS: A postal questionnaire measuring sociodemographic variables, pain
      characteristics, health-related quality of life (HRQoL) and pain-related health
      care utilization, was sent to a sample of 4500 individuals randomly drawn from
      the national population of Iceland. The relationships between sociodemographic
      and pain-related factors and pain-related health care utilization among
      participants reporting chronic pain (>=3 months) were tested by using bivariate
      and multivariate statistical analysis. RESULTS: Among participants reporting
      chronic pain, 53.2% had consulted a health care provider for pain during the
      previous 6 months. Predictors for chronic pain-related health care utilization
      differed between men and women. Interference with life and pain pattern was the
      strongest predictors among women, as compared with interference with life and the
      physical components of HRQoL for men. Pain-related health care utilization was
      not linked to sociodemographic factors. CONCLUSIONS: Pain-related variables are
      better predictors of chronic pain-related health care utilization than
      sociodemographic factors. Even though gender does not predict chronic pain
      related health care utilization, there are gender differences in the
      relationships between pain-related variables and health care utilization. Men
      tend to postpone health care consultations for chronic pain longer than women.

PMID- 25059635
TI  - Alcohol intake and early-onset basal cell carcinoma in a case-control study.
AB  - BACKGROUND: Previous epidemiological studies of overall alcohol intake and basal
      cell carcinoma (BCC) are inconsistent, with some evidence for differences by type
      of alcoholic beverage. While alcohol may enhance the carcinogenicity of
      ultraviolet (UV) radiation, this has not been evaluated in existing
      epidemiological studies. OBJECTIVES: To evaluate alcohol intake in relation to
      early-onset BCC, and explore potential interactions with UV exposure. METHODS:
      Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n
      = 390) under 40 years of age were identified through Yale Dermatopathology.
      Participants provided information on lifetime alcohol intake, including type of
      beverage, during an in-person interview. Self-reported data on indoor tanning and
      outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios
      (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic
      regression in the full sample and in women only. RESULTS: There was no
      statistically significant association between lifetime alcohol intake and early
      onset BCC overall [above median intake vs. no regular alcohol intake (OR 1.10,
      95% CI 0.69-1.73)] or in women only (OR 1.21, 95% CI 0.73-2.01). Similarly,
      intake of red wine, white wine, beer or spirits and mixed drinks was not
      associated with early-onset BCC. In exploratory analyses, we saw limited evidence
      for an interaction (P(interaction) = 0.003), with highest risk for high alcohol
      and high UV exposures, especially in women, but subgroup risk estimates had wide
      and overlapping CIs. CONCLUSIONS: Overall, we did not observe any clear
      association between lifetime alcohol intake and early-onset BCC.

PMID- 25059636
TI  - The MMPI-2 in chronic psychiatric illness.
AB  - While previous studies on the MMPI-2 in patients with schizophrenia and
      depression have used mixed samples of both early stage and chronic psychiatric
      patients. Here, it is investigated whether chronicity itself might have a
      differential effect on the MMPI-2 profiles of these patients and whether
      demoralization 'associated with long-term illness' affects the scales of the MMPI
      2. Thirty long-term patients with schizophrenia, 30 long-term patients with
      depression, and 30 healthy participants completed the MMPI-2. Groups were
      compared on Clinical Scales and on the Restructured Clinical (RC) Scales.
      Patients with schizophrenia differed from patients with depression on 14 MMPI-2
      scales and from healthy controls on 10 scales, generally showing mean UT-scores <
      65, indicating a subjective experience of (near) normal functioning. Patients
      with depression differed from healthy controls on 17 scales mostly with UT-scores
      > 65, indicating impaired functioning. Demoralization was higher in patients with
      depression than in patients with schizophrenia and both psychiatric groups
      differed from the healthy control group. It is concluded that long-term patients
      with depression show impaired functioning and high demoralization, while long
      term patients with schizophrenia surprisingly show near normal functioning and
      less demoralization. 

PMID- 25059637
TI  - Polyhydroxyalkanoate biosynthesis and simultaneous remotion of organic inhibitors
      from sugarcane bagasse hydrolysate by Burkholderia sp.
AB  - Burkholderia sp. F24, originally isolated from soil, was capable of growth on
      xylose and removed organic inhibitors present in a hemicellulosic hydrolysate and
      simultaneously produced poly-3-hydroxybutyrate (P3HB). Using non-detoxified
      hydrolysate, Burkholderia sp. F24 reached a cell dry weight (CDW) of 6.8 g L(-1),
      containing 48 % of P3HB and exhibited a volumetric productivity (PP3HB) of 0.10 g
      L(-1) h(-1). Poly-3-hydroxybutyrate-co-3-hydroxyvalerate copolymers (P3HB-co-3HV)
      were produced using xylose and levulinic acid (LA) as carbon sources. In shake
      flask cultures, the 3HV content in the copolymer increased from 9 to 43 mol% by
      adding LA from 1.0 to 5.0 g L(-1). In high cell density cultivation using
      concentrated hemicellulosic hydrolysate F24 reached 25.04 g L(-1) of CDW
      containing 49 % of P3HB and PP3HB of 0.28 g L(-1 )h(-1). Based on these findings,
      second-generation ethanol and bioplastics from sugarcane bagasse is proposed. 

PMID- 25059638
TI  - Management of chronic Giardia infection.
AB  - Advances in our understanding of chronic giardiasis (CG) may improve our care of
      patients in this stage of the disease. This review proposes a new concept of CG
      and highlights the recent advances in our understanding and management of this
      condition. According to this review, management requires, initially, an accurate
      diagnosis, which may exclude several conditions that can mimic CG. Optimal
      treatment requires a tailored approach which includes the recognition of the
      known modifiable causes of this health condition, assessment of symptoms and
      potential complications, their treatment utilizing, if necessary, a
      multidisciplinary team, and an ongoing monitoring for the effect of therapy -
      weighing the efficacy of individual drugs - all of these together may lead to a
      successful treatment of CG. 

PMID- 25059640
TI  - The effect of chlorhexidine dentifrice or gel versus chlorhexidine mouthwash on
      plaque, gingivitis, bleeding and tooth discoloration: a systematic review.
AB  - OBJECTIVE: To systematically review and evaluate the available scientific
      evidence on the effectiveness of chlorhexidine dentifrice or gel (CHX DF/gel)
      compared to chlorhexidine mouthwash (CHX MW) on plaque, bleeding, gingival
      inflammation and tooth discoloration scores. MATERIAL AND METHODS: PubMed
      MEDLINE, Cochrane-CENTRAL and EMBASE databases were searched to identify
      appropriate studies. RESULTS: Independent screening of the 2256 unique titles and
      abstracts resulted in five publications that met the eligibility criteria.
      Considerable heterogeneity was found between the studies. Three of the five
      studies showed a positive effect on plaque scores in favour of the CHX MW. With
      respect to gingival index and bleeding scores, no significant differences were
      found. Chlorhexidine mouthwash, however, showed a significantly more tooth
      discoloration than the CHX DF/gel. A meta-analysis of the effect on 'de novo'
      plaque formation of CHX DF/gel versus CHX MW resulted in a difference in means of
      0.27 [95% CI: 0.14; 0.39] (P < 0.0001). CONCLUSION: Chlorhexidine gel can be
      successfully formulated and will inhibit plaque growth to some degree, but not to
      the same extent, as a CHX MW. When CHX DF/gel is used in a non-brushing model, it
      is significantly less effective in plaque inhibition compared to CHX MW. Based on
      one study when CHX gel was applied with a finger after brushing, it is
      significantly more effective on plaque scores and the gingival index. The only
      brushing study also with a long follow-up showed that there is no significant
      difference between CHX DF and CHX MW. However, as a corollary, significantly more
      tooth discoloration was observed with the CHX MW. Altogether, the data show that
      when daily oral hygiene cannot be performed, CHX MW is the first product of
      choice.

PMID- 25059639
TI  - Bladder outlet obstruction in women: functional causes.
AB  - Bladder outlet obstruction (BOO) in women has received less focus in the past, as
      compared with BOO in men; however, more recently, studies have further examined
      BOO and voiding dysfunction in women to define the various etiologies, diagnostic
      criteria, and treatment strategies. The differential diagnosis in women is broad
      and includes anatomic, neurologic, and functional etiologies. This review focuses
      on the functional etiologies, including dysfunctional voiding, Fowler's syndrome,
      and primary bladder neck obstruction in adult women. 

PMID- 25059641
TI  - Effect of mitochondrial calcium uniporter blocking on human spermatozoa.
AB  - Calcium (Ca(2+) ) regulates a number of essential processes in spermatozoa.
      Ca(2+) is taken up by mitochondria via the mitochondrial calcium uniporter (mCU).
      Oxygen-bridged dinuclear ruthenium amine complex (Ru360) has been used to study
      mCU because it is a potent and specific inhibitor of this channel. In bovine
      spermatozoa, it has been demonstrated that mitochondrial calcium uptake
      inhibition adversely affects the capacitation process. It has been demonstrated
      in human spermatozoa that mCU blocking, through Ru360, prevents apoptosis;
      however, the contribution of the mCU to normal human sperm function has not been
      studied. Therefore, the aim of this study was to evaluate the effect of mCU
      blocking on human sperm function. Spermatozoa obtained from apparently healthy
      donors were incubated with 5 and 10 MUm Ru360 for 4 h at 37  degrees C. Viability
      was assessed using propidium iodide staining; motility was determined by computer
      aided sperm analysis, adenosine triphosphate (ATP) levels using a luminescence
      based method, mitochondrial membrane potential (DeltaPsim) using JC-1 staining
      and reactive oxygen species (ROS) production using dihydroethidium dye. Our
      results show that mCU blocking significantly reduced total sperm motility and ATP
      levels without affecting sperm viability, DeltaPsim and ROS production. In
      conclusion, mCU contributes to the maintenance of sperm motility and ATP levels
      in human spermatozoa. 

PMID- 25059642
TI  - Acculturation and perceived stress in HIV+ immigrants: depression symptomatology
      in Asian and Pacific Islanders.
AB  - Asians and Pacific Islanders (API) are among the fastest growing minority groups
      within the USA, and this growth has been accompanied by an increase in HIV
      incidence. Between 2000 and 2010, the API HIV infection rate increased from 4.5%
      to 8.7%; however, there is a paucity of HIV-related research for this group, and
      even less is known about the prevalence and correlates of antiretroviral therapy
      adherence behavior, quality of life, impact of stress, and efficacious self
      management among HIV+ API Americans. This paper examines how acculturation and
      perceived stress affect depression symptomatology and treatment seeking in the
      HIV+ API population. A series of cross-sectional audio computer-assisted self
      interviews were conducted with a convenience sample of 50 HIV+ API (29 in San
      Francisco and 21 in New York City). The relationship between acculturation and
      perceived stress was analyzed, and the results indicate that for those HIV+ API
      who reported low or moderate acculturation (as compared to those who reported
      high acculturation), stress was significantly mediated by depression
      symptomology. Interventions to address acculturation and reduce perceived stress
      among API generally and Asians specifically are therefore needed. 

PMID- 25059643
TI  - Pathophysiology of Barrett's esophagus-associated neoplasia: circumferential
      spatial predilection.
AB  - The prevalence rates of Barrett's esophagus (BE) and esophageal adenocarcinoma
      (EAC) arising from BE show striking geographic patterns as they are much more
      common in Western as compared with Asian countries. However, recent
      epidemiological studies indicate that the number of patients with BE and EAC are
      gradually increasing in Asia including Japan, corresponding to the increase in
      prevalence of gastroesophageal reflux disease (GERD). Because the prognosis of
      patients with advanced-stage EAC remains poor, early detection of neoplastic
      lesion in those with BE has led to recent interest in effective treatment.
      Several promising studies have revealed that early neoplasia in BE is mainly
      located in the right anterior wall of the distal esophagus. Interestingly, this
      endoscopic characteristic has been found in both Western and Japanese
      populations. Potential pathophysiologic explanations underlying the
      circumferential distribution of neoplasia in BE include a nonuniform asymmetric
      distribution of esophageal acid exposure, with a tendency toward mucosal acid
      related injury on the right side of the esophageal wall in patients with GERD,
      and the functional structure of the lower esophageal sphincter. Findings of the
      present study should improve lesion detection and aid in developing a target
      biopsy protocol for surveillance of BE.

PMID- 25059644
TI  - Cux1 and Cux2 selectively target basal and apical dendritic compartments of layer
      II-III cortical neurons.
AB  - A number of recent reports implicate the differential regulation of apical and
      basal dendrites in autism disorders and in the higher functions of the human
      brain. They show that apical and basal dendrites are functionally specialized and
      that mechanisms regulating their development have important consequences for
      neuron function. The molecular identity of layer II-III neurons of the cerebral
      cortex is determined by the overlapping expression of Cux1 and Cux2. We
      previously showed that both Cux1 and Cux2 are necessary and nonredundant for
      normal dendrite development of layer II-III neurons. Loss of function of either
      gene reduced dendrite arbors, while overexpression increased dendritic complexity
      and suggested additive functions. We herein characterize the function of Cux1 and
      Cux2 in the development of apical and basal dendrites. By in vivo loss and gain
      of function analysis, we show that while the expression level of either Cux1 or
      Cux2 influences both apical and basal dendrites, they have distinct effects.
      Changes in Cux1 result in a marked effect on the development of the basal
      compartment whereas modulation of Cux2 has a stronger influence on the apical
      compartment. These distinct effects of Cux genes might account for the functional
      diversification of layer II-III neurons into different subpopulations, possibly
      with distinct connectivity patterns and modes of neuron response. Our data
      suggest that by their differential effects on basal and apical dendrites, Cux1
      and Cux2 can promote the integration of layer II-III neurons in the intracortical
      networks in highly specific ways.

PMID- 25059645
TI  - Anisotropic charge distribution and anisotropic van der Waals radius leading to
      intriguing anisotropic noncovalent interactions.
AB  - Although group (IV-VII) nonmetallic elements do not favor interacting with
      anionic species, there are counterexamples including the halogen bond. Such
      binding is known to be related to the charge deficiency because of the adjacent
      atom's electron withdrawing effect, which creates sigma/pi-holes at the bond
      ends. However, a completely opposite behavior is exhibited by N2 and O2, which
      have electrostatically positive/negative character around cylindrical-bond
      surface/bond-ends. Inspired by this, here we elucidate the unusual features and
      origin of the anisotropic noncovalent interactions in the ground and excited
      states of the 2(nd) and 3(rd) row elements belonging to groups IV-VII. The
      anisotropy in charge distributions and van der Waals radii of atoms in such
      molecular systems are scrutinized. This provides an understanding of their
      unusual molecular configuration, binding and recognition modes involved in new
      types of molecular assembling and engineering. This work would lead to the design
      of intriguing molecular systems exploiting anisotropic noncovalent interactions. 

PMID- 25059646
TI  - Inflammation-Induced Downregulation of Butyrate Uptake and Oxidation Is Not
      Caused by a Reduced Gene Expression.
AB  - In ulcerative colitis (UC) the butyrate metabolism is impaired, leading to energy
      deficiency in the colonic cells. The effect of inflammation on the butyrate
      metabolism was investigated. HT-29 cells were incubated with pro-inflammatory
      cytokines (TNF-alpha and/or IFN-gamma) for 1 and 24 h. Cells were additionally
      stimulated with butyrate to investigate its anti-inflammatory potential. Butyrate
      uptake and oxidation were measured using (14)C-labeled butyrate. Gene expression
      of the butyrate metabolism enzymes, interleukin 8 (IL-8; inflammatory marker) and
      villin-1 (VIL-1; epithelial cell damage marker) was measured via quantitative RT
      PCR. Significantly increased IL-8 expression and decreased VIL-1 expression after
      24 h incubation with TNF-alpha and/or IFN-gamma confirmed the presence of
      inflammation. These conditions induced a decrease of both butyrate uptake and
      oxidation, whereas the gene expression was not reduced. Simultaneous incubation
      with butyrate counteracted the reduced butyrate oxidation. In contrast, 1 h
      incubation with TNF-alpha induced a significant increased IL-8 expression and
      decreased butyrate uptake. Incubation with TNF-alpha and/or IFN-gamma for 1 h did
      not induce cell damage nor influence butyrate oxidation. The inflammation-induced
      downregulation of the butyrate metabolism was not caused by a reduced gene
      expression, but appeared consequential to a decreased butyrate uptake. Increasing
      the luminal butyrate levels might have therapeutic potential in UC.

PMID- 25059647
TI  - Ruthenium-catalyzed cycloadditions of 1-haloalkynes with nitrile oxides and
      organic azides: synthesis of 4-haloisoxazoles and 5-halotriazoles.
AB  - (Cyclopentadienyl)(cyclooctadiene) ruthenium(II) chloride [CpRuCl(cod)] catalyzes
      the reaction between nitrile oxides and electronically deficient 1-choro-, 1
      bromo-, and 1-iodoalkynes leading to 4-haloisoxazoles. Organic azides are also
      suitable 1,3-dipoles, resulting in 5-halo-1,2,3-triazoles. These air-tolerant
      reactions can be performed at room temperature with 1.25 equivalents of the
      respective 1,3-dipole relative to the alkyne component. Reactive 1-haloalkynes
      include propiolic amides, esters, ketones, and phosphonates. Post
      functionalization of the halogenated azole products can be accomplished by using
      palladium-catalyzed cross-coupling reactions and by manipulation of reactive
      amide groups. The lack of catalysis observed with [Cp*RuCl(cod)] (Cp* =
      pentamethylcyclopentadienyl) is attributed to steric demands of the Cp* (eta(5)
      C5Me5) ligand in comparison to the parent Cp (eta(5)-C5H5). This hypothesis is
      supported by the poor reactivity of [(eta(5)-C5Me4CF3)RuCl(cod)], which serves as
      a an isosteric mimic of Cp* and as an isoelectronic analogue of Cp.

PMID- 25059648
TI  - G-CSF pretreatment aggravates LPS-associated microcirculatory dysfunction and
      acute liver injury after partial hepatectomy in rats.
AB  - Liver dysfunction is a serious complication in the early phase following major
      liver resection or liver transplantation and might be aggravated by the
      translocation of bacteria and lipopolysaccharide (LPS). As a preventive strategy,
      granulocyte colony-stimulating factor (G-CSF) is prophylactically applied in
      patients who are subjected to major surgery. However, we previously demonstrated
      that G-CSF can induce LPS sensitization. In this study, we aimed to evaluate the
      effects of G-CSF pretreatment on hepatic microcirculatory disturbances and
      postoperative liver dysfunction after 70 % partial hepatectomy (PH) in rats. PH
      alone was well tolerated by all animals (100 % survival rate, slight liver damage
      and inflammation). LPS application after 70 % PH caused moderate inflammation,
      microcirculatory disturbances and hepatic damage and led to a 24-h survival rate
      of 30 % after the operations. In the G-CSF-LPS-PH group, all of the rats died
      within 4 h with severe inflammatory responses and liver damage (i.e., pronounced
      erythrocyte congestion and neutrophil infiltration). Portal hypertension and
      microcirculatory disorders (i.e., inhomogeneous perfusion, sinusoidal dilatation
      and reductions on functional capillary density) were more pronounced in the G-CSF
      LPS-PH group. In conclusion, increased circulating LPS levels were associated
      with an imbalanced inflammatory response and microcirculatory dysfunction that
      preceded liver damage and subsequent dysfunction following surgery. G-CSF
      pretreatment aggravated microcirculatory disturbances and liver damage, which
      might have been related to G-CSF-induced LPS sensitization.

PMID- 25059649
TI  - Chagasic megacolon: enteric neurons and related structures.
AB  - Megacolon, the irreversible dilation of a colonic segment, is a structural sign
      associated with various gastrointestinal disorders. In its hereditary, secondary
      form (e.g. in Hirschsprung's disease), dilation occurs in an originally healthy
      colonic segment due to an anally located, aganglionic zone. In contrast, in
      chronic Chagas' disease, the dilated segment itself displays pathohistological
      changes, and the earliest and most prominent being found was massive loss of
      myenteric neurons. This neuron loss was partial and selective, i.e. some neurons
      containing neuronal nitric oxide synthase and/or vasoactive intestinal peptide
      (VIP) were spared from neuron death. This disproportionate survival of inhibitory
      neurons, however, did not completely correlate with the calibre change along the
      surgically removed, megacolonic segments. A better correlation was observed as to
      potentially contractile muscle tissue elements and the interstitial cells of
      Cajal. Therefore, the decreased densities of alpha-smooth muscle actin- and c-kit
      immunoreactive profiles were estimated along resected megacolonic segments. Their
      lowest values were observed in the megacolonic zones itself, whereas less
      pronounced decreases were found in the non-dilated, transitional zones (oral and
      anal to dilation). In contrast to the myenteric plexus, the submucosal plexus
      displayed only a moderate neuron loss. Neurons co-immunoreactive for VIP and
      calretinin survived disproportionately. As a consequence, these neurons may have
      contributed to maintain the epithelial barrier and allowed the chagasic patients
      to survive for decades, despite their severe disturbance of colonic motility. Due
      to its neuroprotective and neuroeffectory functions, VIP may play a key role in
      the development and duration of chagasic megacolon. 

PMID- 25059650
TI  - Differential basolateral-apical distribution of scavenger receptor, class B, type
      I in cultured cells and the liver.
AB  - The high-density lipoprotein (HDL) receptor, scavenger receptor class B, type I
      (SR-BI), mediates selective cholesteryl ester uptake into the liver, which
      finally results in cholesterol secretion into the bile. Despite several reports,
      the distribution of hepatic SR-BI between the sinusoidal and canalicular
      membranes is still under debate. We present immunohistological data using
      specific markers showing that the bulk of SR-BI is present in sinusoidal
      membranes and, to a lesser extent, in canalicular membranes in murine and human
      liver sections. In addition, SR-BI was detected in preparations of rat liver
      canalicular membranes. We also compared the in vivo findings to HepG2 cells, a
      widely used in vitro hepatocyte model. Interestingly, SR-BI was enriched in bile
      canalicular-like (BC-like) structures in polarized HepG2 cells, which were
      cultivated either conventionally to form a monolayer or in Matrigel to form three
      dimensional structures. Fluorescently labeled HDL was transported into close
      proximity of BC-like structures, whereas HDL labeled with the fluorescent
      cholesterol analog BODIPY-cholesterol was clearly detected within these
      structures. Importantly, similarly to human and mouse liver, SR-BI was localized
      in basolateral membranes in three-dimensional liver microtissues from primary
      human liver cells. Our results demonstrate that SR-BI is highly enriched in
      sinusoidal membranes and is also found in canalicular membranes. There was no
      significant basolateral-apical redistribution of hepatic SR-BI in fasting and
      refeeding experiments in mice. Furthermore, in vitro studies in polarized HepG2
      cells showed explicit differences as SR-BI was highly enriched in BC-like
      structures. These structures are, however, functional and accumulated HDL-derived
      cholesterol. Thus, biological relevant model systems should be employed when
      investigating SR-BI distribution in vitro.

PMID- 25059651
TI  - Flow cytometric determination of 5-bromo-2'-deoxyuridine pharmacokinetics in
      blood serum after intraperitoneal administration to rats and mice.
AB  - 5-Bromo-2'-deoxyuridine (BrdU) is a marker that is widely used to label S-phase
      cells in neurobiological research in most common doses 50 or 100 mg/kg per single
      intraperitoneal (i.p.) injection. However, the important data regarding its
      pharmacokinetics in rodents are still missing. The aim of our study was to
      investigate the BrdU level in serum after a single i.p. injection to adult rats
      (doses: 50 or 100 mg/kg) and adult mice (50 mg/kg). The animals were killed at
      selected time-points after the BrdU injection, and proliferating tumour cells
      (cell lines HCT-116 and HL-60) were co-cultivated with isolated blood sera. BrdU
      incorporated in the DNA of the S-phase tumour cells was stained with an anti-BrdU
      antibody and analysed using flow cytometry. In rats, the efficacies of BrdU
      labelling of S-phase cells in both in vitro and in vivo conditions were compared
      in the 50 and 100 mg/kg groups. According to our results, BrdU was in saturated
      concentration to label almost all S-phase cells for 60 min in both doses and was
      detectable in blood serum until 120 min after the single i.p. injection. However,
      the 100 mg/kg dose of BrdU did not provide a prolonged staining period to offset
      the potentially higher toxicity in comparison with the 50 mg/kg dose. In mice,
      due to their faster metabolism, the concentration of BrdU in blood serum was
      sufficient to label the whole population of S-phase cells for only 15 min after
      the i.p. injection, then dropped rapidly.

PMID- 25059652
TI  - Muscle activity, cross-sectional area, and density following passive standing and
      whole body vibration: A case series.
AB  - OBJECTIVE: To investigate the effects of intermittent passive standing (PS) and
      whole body vibration (WBV) on the electromyography (EMG) activity, cross
      sectional area, and density of lower extremity muscles in individuals with
      chronic motor complete spinal cord injury (SCI). DESIGN: Case series. METHODS:
      Seven adult men with chronic (>=2 years), thoracic motor complete (AIS A-B) SCI
      completed a 40-week course of thrice-weekly intermittent PS-WBV therapy, in a
      flexed knee posture (160 degrees ), for 45 minutes per session at a frequency of
      45 Hz and 0.6-0.7 mm displacement using the WAVE((r)) Pro Plate, with an
      integrated EasyStandTM standing frame. EMG was measured in major lower extremity
      muscles to represent muscle activity during PS-WBV. The cross-sectional area and
      density of the calf muscles were measured using peripheral quantitative computed
      tomography at the widest calf cross-section (66% of the tibia length) at pre- and
      post-intervention. All measured variables were compared between the pre- and post
      intervention measurements to assess change after the PS-WBV intervention.
      RESULTS: PS-WBV acutely induced EMG activity in lower extremity muscles of SCI
      subjects. No significant changes in lower extremity EMG activity, muscle cross
      sectional area, or density were observed following the 40-week intervention.
      CONCLUSIONS: Although acute exposure to PS-WBV can induce electrophysiological
      activity of lower extremity muscles during PS in men with motor complete SCI, the
      PS-WBV intervention for 40 weeks was not sufficient to result in enhanced muscle
      activity, or to increase calf muscle cross-sectional area or density.

PMID- 25059653
TI  - The political epidemiology of HIV.

PMID- 25059654
TI  - Eupolyphaga sinensis Walker demonstrates angiogenic activity and inhibits A549
      cell growth by targeting the KDR signaling pathway.
AB  - Eupolyphaga sinensis Walker has been reported to have anticoagulation,
      antithrombotic, liver protective and antitumor effects. In the present study, the
      inhibitory effects on proliferation of A549 human non-small cell lung cancer
      cells and the underlying mechanisms were examined. Firstly, three solvents, 70%
      ethanol, distilled water and 95% ethanol, were used to extract Eupolyphaga
      sinensis Walker. The MTT assay results demonstrated that the 70% ethanol extract
      more potently reduced the growth of A549 cells and it was therefore adopted in
      the subsequent experiments. Eupolyphaga sinensis Walker 70% ethanol extract
      significantly inhibited A549 cell migration in a time- and dose-dependent manner
      and inhibited human umbilical vein endothelial cell proliferation, migration and
      tube formation. Furthermore, Eupolyphaga sinensis Walker 70% ethanol extract
      effectively inhibited blood vessel formation in the established tissue model for
      angiogenesis. In addition, Eupolyphaga sinensis Walker 70% ethanol extract was
      demonstrated to inhibit the autophosphorylation of KDR, and downregulate the
      subsequent activation of AKT and extracellular signal regulated kinase (ERK)1/2
      in A549 cells. In conclusion, these findings demonstrated that the antitumor
      mechanism of Eupolyphaga sinensis Walker 70% ethanol extract was through
      inhibiting angiogenesis. It functioned by interrupting the autophosphorylation of
      KDR and subsequently, AKT and ERK1/2. 

PMID- 25059655
TI  - Impact of FDA Actions, DTCA, and Public Information on the Market for Pain
      Medication.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most important
      classes of prescription drugs used by primary care physicians to manage pain. The
      NSAID class of products has a somewhat controversial history, around which a
      complex regulatory and informational environment has developed. This history
      includes a boxed warning mandated by the Food and Drug Administration (FDA) for
      all NSAIDs in 2005. We investigate the impact that various information shocks
      have had on the use of prescription medications for pain in primary care in the
      USA. We accomplish this by extracting data on nearly 600,000 patients from a
      unique nationwide electronic medical record database and estimate the probability
      of any active prescription for the four types of pain medications as a function
      of FDA actions, advertising, media coverage, and patient characteristics. We find
      that even after accounting for multiple sources of information, the FDA label
      changes and boxed warnings had a significant effect on pain medication
      prescribing. The boxed warning did not have the same impact on the use of all
      NSAID inhibitors. We find that the boxed warning reduced the use of NSAID COX-2
      inhibitor use, which was the focus of much of the press attention. In contrast,
      however, the warning actually increased the use of non-COX-2 NSAID inhibitors.
      Thus, the efficacy of the FDA's black box warning is clearly mixed.

PMID- 25059656
TI  - Anticipated motivation for genetic testing among smokers, nonsmokers, and former
      smokers: an exploratory qualitative study of decision making.
AB  - OBJECTIVES: This qualitative study explores the public's interest in genetic
      testing related to cigarette smoking, comparing the public's motivations with
      researchers' intentions for this technology. METHODS: Adult nonsmokers (n=463),
      former smokers (n=163), and current smokers (n=129) completed an online survey.
      Within a hypothetical scenario, respondents decided whether they desired genetic
      testing related to smoking and explained their decision making. A non-parametric
      Kruskal-Wallis test was used to compare the interest in genetic testing by
      smoking history group. Inductive content analysis was used to investigate
      respondents' explanations for their testing decisions. RESULTS: Most nonsmokers
      (64%) and former smokers (58%) did not want genetic testing. While most current
      daily smokers were interested in testing (56%), most current occasional smokers
      were not (52%). Respondents' decision-making explanations were categorized into 3
      major themes: Causality, Relevancy and Utility (e.g. personal benefits or harms).
      The use of causality, relevancy and utility explanations varied by smoking
      history. Notable perceived benefits of testing included recreation and altruism.
      Notable perceived harms included fear of fatalistic thoughts and concern about
      genetic discrimination. CONCLUSIONS: Interest in genetic testing was highest
      among current daily smokers, despite potential utility in other groups. Although
      respondents' motivations for testing paralleled researchers' intentions of
      tailoring smoking cessation therapies and increasing motivation to quit or
      abstain, respondents also raised alternative motivations and fears that
      healthcare providers would need to address.

PMID- 25059657
TI  - Harnessing the unique structural properties of isolated alpha-helices.
AB  - The alpha-helix is a ubiquitous secondary structural element that is almost
      exclusively observed in proteins when stabilized by tertiary or quaternary
      interactions. However, beginning with the unexpected observations of alpha-helix
      formation in the isolated C-peptide in ribonuclease A, there is growing evidence
      that a significant percentage (0.2%) of all proteins contain isolated stable
      single alpha-helical domains (SAH). These SAH domains provide unique structural
      features essential for normal protein function. A subset of SAH domains contain a
      characteristic ER/K motif, composed of a repeating sequence of ~4 consecutive
      glutamic acids followed by ~4 consecutive basic arginine or lysine (R/K)
      residues. The ER/K alpha-helix, also termed the ER/K linker, has been extensively
      characterized in the context of the myosin family of molecular motors and is
      emerging as a versatile structural element for protein and cellular engineering
      applications. Here, we review the structure and function of SAH domains, as well
      as the tools to identify them in natural proteins. We conclude with a discussion
      of recent studies that have successfully used the modular ER/K linker for
      engineering chimeric myosin proteins with altered mechanical properties, as well
      as synthetic polypeptides that can be used to monitor and systematically modulate
      protein interactions within cells. 

PMID- 25059658
TI  - Mycobacterium tuberculosis DinG is a structure-specific helicase that unwinds G4
      DNA: implications for targeting G4 DNA as a novel therapeutic approach.
AB  - The significance of G-quadruplexes and the helicases that resolve G4 structures
      in prokaryotes is poorly understood. The Mycobacterium tuberculosis genome is GC
      rich and contains >10,000 sequences that have the potential to form G4
      structures. In Escherichia coli, RecQ helicase unwinds G4 structures. However,
      RecQ is absent in M. tuberculosis, and the helicase that participates in G4
      resolution in M. tuberculosis is obscure. Here, we show that M. tuberculosis DinG
      (MtDinG) exhibits high affinity for ssDNA and ssDNA translocation with a 5' -> 3'
      polarity. Interestingly, MtDinG unwinds overhangs, flap structures, and forked
      duplexes but fails to unwind linear duplex DNA. Our data with DNase I
      footprinting provide mechanistic insights and suggest that MtDinG is a 5' -> 3'
      polarity helicase. Notably, in contrast to E. coli DinG, MtDinG catalyzes
      unwinding of replication fork and Holliday junction structures. Strikingly, we
      find that MtDinG resolves intermolecular G4 structures. These data suggest that
      MtDinG is a multifunctional structure-specific helicase that unwinds model
      structures of DNA replication, repair, and recombination as well as G4
      structures. We finally demonstrate that promoter sequences of M. tuberculosis
      PE_PGRS2, mce1R, and moeB1 genes contain G4 structures, implying that G4
      structures may regulate gene expression in M. tuberculosis. We discuss these data
      and implicate targeting G4 structures and DinG helicase in M. tuberculosis could
      be a novel therapeutic strategy for culminating the infection with this pathogen.

PMID- 25059659
TI  - Structural determinants for binding of sorting nexin 17 (SNX17) to the
      cytoplasmic adaptor protein Krev interaction trapped 1 (KRIT1).
AB  - Sorting nexin 17 (SNX17) is a member of the family of cytoplasmic sorting nexin
      adaptor proteins that regulate endosomal trafficking of cell surface proteins.
      SNX17 localizes to early endosomes where it directly binds NPX(Y/F) motifs in the
      cytoplasmic tails of its target receptors to mediate their rates of endocytic
      internalization, recycling, and/or degradation. SNX17 has also been implicated in
      mediating cell signaling and can interact with cytoplasmic proteins. KRIT1 (Krev
      interaction trapped 1), a cytoplasmic adaptor protein associated with cerebral
      cavernous malformations, has previously been shown to interact with SNX17. Here,
      we demonstrate that SNX17 indeed binds directly to KRIT1 and map the binding to
      the second Asn-Pro-Xaa-Tyr/Phe (NPX(Y/F)) motif in KRIT1. We further characterize
      the interaction as being mediated by the FERM domain of SNX17. We present the co
      crystal structure of SNX17-FERM with the KRIT1-NPXF2 peptide to 3.0 A resolution
      and demonstrate that the interaction is highly similar in structure and binding
      affinity to that between SNX17 and P-selectin. We verify the molecular details of
      the interaction by site-directed mutagenesis and pulldown assay and thereby
      confirm that the major binding site for SNX17 is confined to the NPXF2 motif in
      KRIT1. Taken together, our results verify a direct interaction between SNX17 and
      KRIT1 and classify KRIT1 as a SNX17 binding partner. 

PMID- 25059660
TI  - Src kinase determines the dynamic exchange of the docking protein NEDD9 (neural
      precursor cell expressed developmentally down-regulated gene 9) at focal
      adhesions.
AB  - Dynamic exchange of molecules between the cytoplasm and integrin-based focal
      adhesions provides a rapid response system for modulating cell adhesion.
      Increased residency time of molecules that regulate adhesion turnover contributes
      to adhesion stability, ultimately determining migration speed across two
      dimensional surfaces. In the present study we test the role of Src kinase in
      regulating dynamic exchange of the focal adhesion protein NEDD9/HEF1/Cas-L. Using
      either chemical inhibition or fibroblasts genetically null for Src together with
      fluorescence recovery after photobleaching (FRAP), we find that Src significantly
      reduces NEDD9 exchange at focal adhesions. Analysis of NEDD9 mutant constructs
      with the two major Src-interacting domains disabled revealed the greatest effects
      were due to the NEDD9 SH2 binding domain. This correlated with a significant
      change in two-dimensional migratory speed. Given the emerging role of NEDD9 as a
      regulator of focal adhesion stability, the time of NEDD9 association at the focal
      adhesions is key in modulating rates of migration and invasion. Our study
      suggests that Src kinase activity determines NEDD9 exchange at focal adhesions
      and may similarly modulate other focal adhesion-targeted Src substrates to
      regulate cell migration. 

PMID- 25059661
TI  - Cyanobacteriochrome SesA is a diguanylate cyclase that induces cell aggregation
      in Thermosynechococcus.
AB  - Cyanobacteria have unique photoreceptors, cyanobacteriochromes, that show diverse
      spectral properties to sense near-UV/visible lights. Certain cyanobacteriochromes
      have been shown to regulate cellular phototaxis or chromatic acclimation of
      photosynthetic pigments. Some cyanobacteriochromes have output domains involved
      in bacterial signaling using a second messenger cyclic dimeric GMP (c-di-GMP),
      but its role in cyanobacteria remains elusive. Here, we characterize the
      recombinant Tlr0924 from a thermophilic cyanobacterium Thermosynechococcus
      elongatus, which was expressed in a cyanobacterial system. The protein reversibly
      photoconverts between blue- and green-absorbing forms, which is consistent with
      the protein prepared from Escherichia coli, and has diguanylate cyclase activity,
      which is enhanced 38-fold by blue light compared with green light. Therefore,
      Tlr0924 is a blue light-activated diguanylate cyclase. The protein's relatively
      low affinity (10.5 mM) for Mg(2+), which is essential for diguanylate cyclase
      activity, suggests that Mg(2+) might also regulate c-di-GMP signaling. Finally,
      we show that blue light irradiation under low temperature is responsible for
      Thermosynechococcus vulcanus cell aggregation, which is abolished when tlr0924 is
      disrupted, suggesting that Tlr0924 mediates blue light-induced cell aggregation
      by producing c-di-GMP. Given our results, we propose the name "sesA (sessility
      A)" for tlr0924. This is the first report for cyanobacteriochrome-dependent
      regulation of a sessile/planktonic lifestyle in cyanobacteria via c-di-GMP.

PMID- 25059662
TI  - Mutational analysis of the integral membrane methyltransferase isoprenylcysteine
      carboxyl methyltransferase (ICMT) reveals potential substrate binding sites.
AB  - The eukaryotic integral membrane enzyme isoprenylcysteine carboxyl
      methyltransferase (ICMT) methylates the carboxylate of a lipid-modified cysteine
      at the C terminus of its protein substrates. This is the final post-translational
      modification of proteins containing a CAAX motif, including the oncoprotein Ras,
      and therefore, ICMT may serve as a therapeutic target in cancer development. ICMT
      has no discernible sequence homology with soluble methyltransferases, and aspects
      of its catalytic mechanism are unknown. For example, how both the methyl donor S
      adenosyl-l-methionine (AdoMet), which is water-soluble, and the methyl acceptor
      isoprenylcysteine, which is lipophilic, are recognized within the same active
      site is not clear. To identify regions of ICMT critical for activity, we combined
      scanning mutagenesis with methyltransferase assays. We mutated nearly half of the
      residues of the ortholog of human ICMT from Anopheles gambiae and observed
      reduced or undetectable catalytic activity for 62 of the mutants. The crystal
      structure of a distantly related prokaryotic methyltransferase (Ma Mtase), which
      has sequence similarity with ICMT in its AdoMet binding site but methylates
      different substrates, provides context for the mutational analysis. The data
      suggest that ICMT and Ma MTase bind AdoMet in a similar manner. With regard to
      residues potentially involved in isoprenylcysteine binding, we identified
      numerous amino acids within transmembrane regions of ICMT that dramatically
      reduced catalytic activity when mutated. Certain substitutions of these caused
      substrate inhibition by isoprenylcysteine, suggesting that they contribute to the
      isoprenylcysteine binding site. The data provide evidence that the active site of
      ICMT spans both cytosolic and membrane-embedded regions of the protein. 

PMID- 25059664
TI  - NLRP3 inflammasome mediates albumin-induced renal tubular injury through impaired
      mitochondrial function.
AB  - Proteinuria serves as a direct causative factor of renal tubular cell injury and
      is highly associated with the progression of chronic kidney disease via uncertain
      mechanisms. Recently, evidence demonstrated that both NLRP3 inflammasome and
      mitochondria are involved in the chronic kidney disease progression. The present
      study was undertaken to examine the role of NLRP3 inflammasome/mitochondria axis
      in albumin-induced renal tubular injury. In patients with proteinuria, NLRP3 was
      significantly up-regulated in tubular epithelial cells and was positively
      correlated with the severity of proteinuria. In agreement with these results,
      albumin remarkably activated NLRP3 inflammasome in both in vitro renal tubular
      cells and in vivo kidneys in parallel with significant epithelial cell phenotypic
      alteration and cell apoptosis. Genetic disruption of NLRP3 inflammasome
      remarkably attenuated albumin-induced cell apoptosis and phenotypic changes under
      both in vitro and in vivo conditions. In addition, albumin treatment resulted in
      a significant mitochondrial abnormality as evidenced by the impaired function and
      morphology, which was markedly reversed by invalidation of NLRP3/caspase-1
      signaling pathway. Interestingly, protection of mitochondria function by
      Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP) or cyclosporin A (CsA)
      robustly attenuated albumin-induced injury in mouse proximal tubular cells.
      Collectively, these findings demonstrated a pathogenic role of NLRP3
      inflammasome/caspase-1/mitochondria axis in mediating albumin-induced renal
      tubular injury. The discovery of this novel axis provides some potential targets
      for the treatment of proteinuria-associated renal injury. 

PMID- 25059663
TI  - TIF1gamma protein regulates epithelial-mesenchymal transition by operating as a
      small ubiquitin-like modifier (SUMO) E3 ligase for the transcriptional regulator
      SnoN1.
AB  - Epithelial-mesenchymal transition (EMT) is a fundamental cellular process that
      contributes to epithelial tissue morphogenesis during normal development and in
      tumor invasiveness and metastasis. The transcriptional regulator SnoN robustly
      influences EMT in response to the cytokine TGFbeta, but the mechanisms that
      regulate the fundamental role of SnoN in TGFbeta-induced EMT are not completely
      understood. Here we employ interaction proteomics to uncover the signaling
      protein TIF1gamma as a specific interactor of SnoN1 but not the closely related
      isoform SnoN2. A 16-amino acid peptide within a unique region of SnoN1 mediates
      the interaction of SnoN1 with TIF1gamma. Strikingly, although TIF1gamma is
      thought to act as a ubiquitin E3 ligase, we find that TIF1gamma operates as a
      small ubiquitin-like modifier (SUMO) E3 ligase that promotes the sumoylation of
      SnoN1 at distinct lysine residues. Importantly, TIF1gamma-induced sumoylation is
      required for the ability of SnoN1 to suppress TGFbeta-induced EMT, as assayed by
      the disruption of the morphogenesis of acini in a physiologically relevant three
      dimensional model of normal murine mammary gland (NMuMG) epithelial cells.
      Collectively, our findings define a novel TIF1gamma-SnoN1 sumoylation pathway
      that plays a critical role in EMT and has important implications for our
      understanding of TGFbeta signaling and diverse biological processes in normal
      development and cancer biology. 

PMID- 25059665
TI  - Binding of tissue-type plasminogen activator to the glucose-regulated protein 78
      (GRP78) modulates plasminogen activation and promotes human neuroblastoma cell
      proliferation in vitro.
AB  - The glucose-regulated protein 78 (GRP78) is a plasminogen (Pg) receptor on the
      cell surface. In this study, we demonstrate that GRP78 also binds the tissue-type
      plasminogen activator (t-PA), which results in a decrease in K(m) and an increase
      in the V(max) for both its amidolytic activity and activation of its substrate,
      Pg. This results in accelerated Pg activation when GRP78, t-PA, and Pg are bound
      together. The increase in t-PA activity is the result of a mechanism involving a
      t-PA lysine-dependent binding site in the GRP78 amino acid sequence
      (98)LIGRTWNDPSVQQDIKFL(115). We found that GRP78 is expressed on the surface of
      neuroblastoma SK-N-SH cells where it is co-localized with the voltage-dependent
      anion channel (VDAC), which is also a t-PA-binding protein in these cells. We
      demonstrate that both Pg and t-PA serve as a bridge between GRP78 and VDAC
      bringing them together to facilitate Pg activation. t-PA induces SK-N-SH cell
      proliferation via binding to GRP78 on the cell surface. Furthermore, Pg binding
      to the COOH-terminal region of GRP78 stimulates cell proliferation via its
      microplasminogen domain. This study confirms previous findings from our
      laboratory showing that GRP78 acts as a growth factor-like receptor and that its
      association with t-PA, Pg, and VDAC on the cell surface may be part of a system
      controlling cell growth.

PMID- 25059667
TI  - Negative regulation of Toll-like receptor-4 signaling through the binding of
      glycosylphosphatidylinositol-anchored glycoprotein, CD14, with the sialic acid
      binding lectin, CD33.
AB  - When monocyte-derived immature dendritic cells (imDCs) were stimulated with LPS
      in the presence of anti-CD33/Siglec-3 mAb, the production of IL-12 and
      phosphorylation of NF-kappaB decreased significantly. The cell surface proteins
      of imDCs were chemically cross-linked, and CD33-linked proteins were analyzed by
      SDS-PAGE and immunoblotting. It was CD14 that was found to be cross-linked with
      CD33. A proximity ligation assay also indicated that CD33 was colocalized with
      CD14 on the cell surface of imDCs. Sialic acid-dependent binding of CD33 to CD14
      was confirmed by a plate assay using recombinant CD33 and CD14. Three types of
      cells (HEK293T cells expressing the LPS receptor complex (Toll-like receptor
      (TLR) cells), and the LPS receptor complex plus either wild-type CD33 (TLR/CD33WT
      cells) or mutated CD33 without sialic acid-binding activity (TLR/CD33RA cells))
      were prepared, and then the binding and uptake of LPS were investigated. Although
      the level of LPS bound on the cell surface was similar among these cells, the
      uptake of LPS was reduced in TLR/CD33WT cells. A higher level of CD14-bound LPS
      and a lower level of TLR4-bound LPS were detected in TLR/CD33WT cells compared
      with the other two cell types, probably due to reduced presentation of LPS from
      CD14 to TLR4. Phosphorylation of NF-kappaB after stimulation with LPS was also
      compared. Wild-type CD33 but not mutated CD33 significantly reduced the
      phosphorylation of NF-kappaB. These results suggest that CD14 is an endogenous
      ligand for CD33 and that ligation of CD33 with CD14 modulates with the
      presentation of LPS from CD14 to TLR4, leading to down-regulation of TLR4
      mediated signaling. 

PMID- 25059666
TI  - MicroRNA-21 promotes glioblastoma tumorigenesis by down-regulating insulin-like
      growth factor-binding protein-3 (IGFBP3).
AB  - Despite advances in surgery, imaging, chemotherapy, and radiation, patients with
      glioblastoma multiforme (GBM), the most common histological subtype of glioma,
      have an especially dismal prognosis; >70% of GBM patients die within 2 years of
      diagnosis. In many human cancers, the microRNA miR-21 is overexpressed, and
      accumulating evidence indicates that it functions as an oncogene. Here, we report
      that miR-21 is overexpressed in human GBM cell lines and tumor tissue. Moreover,
      miR-21 expression in GBM patient samples is inversely correlated with patient
      survival. Knockdown of miR-21 in GBM cells inhibited cell proliferation in vitro
      and markedly inhibited tumor formation in vivo. A number of known miR-21 targets
      have been identified previously. By microarray analysis, we identified and
      validated insulin-like growth factor (IGF)-binding protein-3 (IGFBP3) as a novel
      miR-21 target gene. Overexpression of IGFBP3 in glioma cells inhibited cell
      proliferation in vitro and inhibited tumor formation of glioma xenografts in
      vivo. The critical role that IGFBP3 plays in miR-21-mediated actions was
      demonstrated by a rescue experiment, in which IGFBP3 knockdown in miR-21KD
      glioblastoma cells restored tumorigenesis. Examination of tumors from GBM
      patients showed that there was an inverse relationship between IGFBP3 and miR-21
      expression and that increased IGFBP3 expression correlated with better patient
      survival. Our results identify IGFBP3 as a novel miR-21 target gene in
      glioblastoma and suggest that the oncogenic miRNA miR-21 down-regulates the
      expression of IGFBP3, which acts as a tumor suppressor in human glioblastoma. 

PMID- 25059668
TI  - Amino acid derivatives as bitter taste receptor (T2R) blockers.
AB  - In humans, the 25 bitter taste receptors (T2Rs) are activated by hundreds of
      structurally diverse bitter compounds. However, only five antagonists or bitter
      blockers are known. In this study, using molecular modeling guided site-directed
      mutagenesis, we elucidated the ligand-binding pocket of T2R4. We found seven
      amino acids located in the extracellular side of transmembrane 3 (TM3), TM4,
      extracellular loop 2 (ECL2), and ECL3 to be involved in T2R4 binding to its
      agonist quinine. ECL2 residues Asn-173 and Thr-174 are essential for quinine
      binding. Guided by a molecular model of T2R4, a number of amino acid derivatives
      were screened for their ability to bind to T2R4. These predictions were tested by
      calcium imaging assays that led to identification of gamma-aminobutryic acid
      (GABA) and Nalpha,Nalpha-bis(carboxymethyl)-L-lysine (BCML) as competitive
      inhibitors of quinine-activated T2R4 with an IC50 of 3.2 +/- 0.3 MUM and 59 +/-
      18 nM, respectively. Interestingly, pharmacological characterization using a
      constitutively active mutant of T2R4 reveals that GABA acts as an antagonist,
      whereas BCML acts as an inverse agonist on T2R4. Site-directed mutagenesis
      confirms that the two novel bitter blockers share the same orthosteric site as
      the agonist quinine. The signature residues Ala-90 and Lys-270 play important
      roles in interacting with BCML and GABA, respectively. This is the first report
      to characterize a T2R endogenous antagonist and an inverse agonist. The novel
      bitter blockers will facilitate physiological studies focused on understanding
      the roles of T2Rs in extraoral tissues.

PMID- 25059670
TI  - Scalable high-fidelity growth of semiconductor nanorod arrays with controlled
      geometry for photovoltaic devices using block copolymers.
AB  - Controlled density semiconducting oxide arrays are highly desirable for matching
      nanometer length scales specific to emerging applications. This work demonstrates
      a facile one-step method for templating hydrothermal growth which provides arrays
      with high-fidelity tuning of nanorod spacing and diameter. This solution-based
      method leverages the selective swelling of block copolymer micelle templates,
      which can be rationally designed by tuning molecular weight and volume fraction. 

PMID- 25059671
TI  - Usability of mobile technology to screen for drug-drug interactions in kidney
      transplant patients.
AB  - BACKGROUND AND OBJECTIVES: Kidney transplant recipients are at increased risk for
      adverse safety events related to reduced renal function and polypharmacy. Health
      information technology tools have a precautionary role in improving safety in
      patients with kidney transplants who are at risk of drug-drug interactions.
      MATERIALS AND METHODS: Usability testing of a drug-drug interaction inquiry
      system on a convenience sample of kidney transplant patients and their family
      members was conducted between January and April 2013 by a single interviewer.
      Each participant was provided with 35 tasks to complete on a cell phone with a
      manual keypad. The tasks were classified according to how it was completed:
      easily completed, noncritical error, or critical error (where a participant was
      unable to complete the given task without intervention by the interviewer). The
      final task was timed using a stop watch. RESULTS: Out of a total of 16
      volunteers, 15 completed the testing. The median time to complete the final task
      was 4 min (range: 2-9). In a cumulative total of 525 tasks, 33 critical errors
      were noted. Twelve participants had one or more critical errors. The most
      frequent critical errors were related to typing and spelling mistakes. Twelve out
      15 participants were able to complete the final task without any critical errors.
      CONCLUSIONS: Understanding transplant patients' preference in technology use and
      adapting applications to a variety of technological portals will ensure the most
      effective use of targeted interventions in patient safety, particularly when
      applied to preventing drug-drug interactions.

PMID- 25059672
TI  - Diisocyanates, occupational asthma and IgE antibody: implications for hazard
      characterization.
AB  - Sensitization of the respiratory tract by chemicals resulting in rhinitis and
      asthma is an important occupational health issue. Occupational asthma is
      associated with significant morbidity and can be fatal. Tests for the
      identification and characterization of chemicals with the potential to cause
      sensitization of the respiratory tract are lacking. In spite of sustained
      interest there are no validated or widely accepted methods available, and this
      presents toxicologists with a considerable challenge. One important constraint on
      the development of appropriate testing strategies has been uncertainty and
      controversy about the immunological mechanisms through which chemicals may induce
      sensitization of the respiratory tract. By analogy with protein respiratory
      allergy it is legitimate to consider that IgE antibody-dependent mechanisms may
      play a pivotal role. However, although many aspects of chemical respiratory
      allergy are consistent with reactions caused by IgE antibody, uncertainty remains
      because among patients with occupational asthma caused by chemical respiratory
      allergens there are commonly a proportion, and sometimes a significant
      proportion, of subjects that lack detectable IgE antibody. Here we consider the
      relevance of IgE antibody responses for the development of a chemical respiratory
      allergy to diisocyanates. A case is made that IgE antibody responses are, either
      directly or indirectly, closely associated with occupational asthma to the
      diisocyanates (and to other chemical respiratory allergens). As such the argument
      is advanced here that IgE antibody represents an appropriate readout for the
      characterization of chemical respiratory allergens, and that uncertainty about
      mode of action should no longer represent a hurdle in the development of suitable
      test methods.

PMID- 25059669
TI  - Intracellular carbonic anhydrase activity sensitizes cancer cell pH signaling to
      dynamic changes in CO2 partial pressure.
AB  - Carbonic anhydrase (CA) enzymes catalyze the chemical equilibration among CO2,
      HCO3(-) and H(+). Intracellular CA (CAi) isoforms are present in certain types of
      cancer, and growing evidence suggests that low levels correlate with disease
      severity. However, their physiological role remains unclear. Cancer cell CAi
      activity, measured as cytoplasmic CO2 hydration rate (kf), ranged from high in
      colorectal HCT116 (~2 s(-1)), bladder RT112 and colorectal HT29, moderate in
      fibrosarcoma HT1080 to negligible (i.e. spontaneous kf = 0.18 s(-1)) in cervical
      HeLa and breast MDA-MB-468 cells. CAi activity in cells correlated with CAII
      immunoreactivity and enzymatic activity in membrane-free lysates, suggesting that
      soluble CAII is an important intracellular isoform. CAi catalysis was not
      obligatory for supporting acid extrusion by H(+) efflux or HCO3(-) influx, nor
      for maintaining intracellular pH (pHi) uniformity. However, in the absence of CAi
      activity, acid loading from a highly alkaline pHi was rate-limited by HCO3(-)
      supply from spontaneous CO2 hydration. In solid tumors, time-dependence of blood
      flow can result in fluctuations of CO2 partial pressure (pCO2) that disturb
      cytoplasmic CO2-HCO3(-)-H(+) equilibrium. In cancer cells with high CAi activity,
      extracellular pCO2 fluctuations evoked faster and larger pHi oscillations.
      Functionally, these resulted in larger pH-dependent intracellular [Ca(2+)]
      oscillations and stronger inhibition of the mTORC1 pathway reported by S6 kinase
      phosphorylation. In contrast, the pHi of cells with low CAi activity was less
      responsive to pCO2 fluctuations. Such low pass filtering would "buffer" cancer
      cell pHi from non-steady-state extracellular pCO2. Thus, CAi activity determines
      the coupling between pCO2 (a function of tumor perfusion) and pHi (a potent
      modulator of cancer cell physiology).

PMID- 25059673
TI  - Is oxytocin a maternal-foetal signalling molecule at birth? Implications for
      development.
AB  - The neuropeptide oxytocin was first noted for its capacity to promote uterine
      contractions and facilitate delivery in mammals. The study of oxytocin has grown
      to include awareness that this peptide is a neuromodulator with broad effects
      throughout the body. Accumulating evidence suggests that oxytocin is a powerful
      signal to the foetus, helping to prepare the offspring for the extrauterine
      environment. Concurrently, the use of exogenous oxytocin or other drugs to
      manipulate labour has become common practice. The use of oxytocin to expedite
      labour and minimise blood loss improves both infant and maternal survival under
      some conditions. However, further investigations are needed to assess the
      developmental consequences of changes in oxytocin, such as those associated with
      pre-eclampsia or obstetric manipulations associated with birth. This review
      focuses on the role of endogenous and exogenous oxytocin as a neurochemical
      signal to the foetal nervous system. We also examine the possible developmental
      consequences, including those associated with autism spectrum disorder, that
      arise from exogenous oxytocin supplementation during labour. 

PMID- 25059674
TI  - Protective effects of piperine against copper-ascorbate induced toxic injury to
      goat cardiac mitochondria in vitro.
AB  - Piperine, the main alkaloid of black pepper, Piper nigrum Linn., is an important
      Indian spice used in traditional food and medicine in India. In the present
      study, we investigated the antioxidant activities of piperine against copper
      ascorbate induced toxic injury to mitochondria obtained from a goat heart, in
      vitro. Incubation of isolated cardiac mitochondria with copper-ascorbate resulted
      in elevated levels of lipid peroxidation and protein carbonylation of the
      mitochondrial membrane, a reduced level of mitochondrial GSH and altered status
      of antioxidant enzymes as well as decreased activities of pyruvate dehydrogenase
      and the Kreb's cycle enzymes, altered mitochondrial morphology, mitochondrial
      swelling, di-tyrosine level and mitochondrial DNA damage. All these changes were
      found to be ameliorated when the cardiac mitochondria were co-incubated with
      copper-ascorbate and piperine, in vitro. Piperine, in our in vitro experiments,
      was found to scavenge hydrogen peroxide, superoxide anion free radicals, hydroxyl
      radicals and DPPH radicals, in a chemically defined system, indicating that this
      compound may provide protection to cardiac mitochondria against copper-ascorbate
      induced toxic injury through its antioxidant activities. The results of this
      study suggest that piperine may be considered as a future therapeutic antioxidant
      and may be used singly or as a co-therapeutic in the treatment of diseases
      associated with mitochondrial oxidative stress. 

PMID- 25059675
TI  - Chinese community-dwelling elders' needs: promoting ageing in place.
AB  - BACKGROUND: 'Ageing in place' is widely promoted as a response to global ageing
      and increased demand for services, but little evidence is available about what
      older people think they need in terms of services and supports to remain at home.
      AIM: To investigate older people's needs when ageing in place in order to provide
      evidence to inform policies and strategies promoting the option of ageing in
      place. METHODS: A total of 568 elderly persons in Hangzhou, China, were surveyed
      in 2009-2011 using a modified questionnaire validated in the USA and China.
      RESULTS: Overall, 88.9% of older adults were satisfied with the community in
      which they live; 97.2% were satisfied with life quality. Health problems and
      healthcare access difficulty increased with age. House repairs and housework were
      the most troubling. Respondents identified high need for social and health
      promotion services and this varied across age groups. LIMITATIONS: Cultural
      adaptation and validation of the questionnaire could have been influenced by
      differences in socioeconomic and cultural factors. The sample excluded older
      adults with disabilities, bed-ridden and/or unable to communicate thus limiting
      the scope of relevance. CONCLUSION: A majority of older adult respondents ageing
      at home lived a relatively healthy life; however, they required more
      comprehensive health insurance to cover costs of long-term health problems and
      access to home care support. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The
      needs of community-dwelling older Chinese people in the Xiacheng District are not
      being fully met and much remains be done to increase community and regional
      capacity before ageing in place can be promoted as a policy strategy. More
      generally, nursing and health policies geared to enhance the self-sufficiency of
      older people residing in their communities must draw upon evidence of assessed
      needs and client perspectives of their requirements before services can be
      designed and delivered.

PMID- 25059676
TI  - The utilisation and diagnostic yield of radiological imaging in a specialist
      functional GI disorder clinic: an 11-year retrospective study.
AB  - OBJECTIVES: The term functional gastrointestinal disorders (FGID) describes
      various aggregations of chronic gastrointestinal (GI) symptoms not explained by
      identifiable organic pathology; accordingly, their diagnosis rests on symptom
      based criteria and a process of exclusion. Evidence is lacking on the appropriate
      use of abdominal imaging studies (AIS) in FGIDs. METHODS: We investigated the
      utilisation of AIS (site, modality, diagnostic yield/significance) at a tertiary
      FGID clinic over an 11-year period. RESULTS: Of 1,621 patients, 507 (31%; 67.5%
      women, mean age 43.9 +/- 17.37 years) referred from primary care had 997 AIS (1.7
      per patient): ultrasonography (US) 36.1%, fluoroscopy (FLS) 28.8%, computed
      tomography (CT) 19.6%, plain radiography (PR) 13.5%, nuclear medicine (NM) 1%).
      Of the 997 AIS, 55.6% (554/997) were normal. Of the AIS with positive findings,
      9.9% (62/625) were deemed 'probably significant' and 14.7% (92/625)
      'significant'. Of the CT and FLS studies, 12.3% and 13.6%, respectively, yielded
      'significant' abnormalities compared to 2.2% of the US studies and 2.1% of the PR
      studies. CT identified five of seven neoplasms, associated with male sex,
      increasing age and symptom onset after age 50 years. CONCLUSIONS: This study
      confirmed low use of AIS in tertiary FGID clinics and a high proportion of normal
      studies. Barium swallow/meal and CT were more likely to identify 'probably
      significant' or 'significant' findings, including neoplasms. KEY POINTS: Imaging
      referral rates from a specialist functional gastrointestinal disorder clinic are
      low. Despite this, normal studies are still frequent in those who are imaged.
      Ultrasonography was the most frequent investigation, yet yielded significant
      findings infrequently. Abdominal radiographs accounted for 13.5% of
      investigations yet were normal in 71.8 %. CT and fluoroscopy were more likely to
      yield positive findings.

PMID- 25059677
TI  - 3D FIESTA pulse sequence for assessing renal artery stenosis: is it a reliable
      application in unenhanced magnetic resonance angiography?
AB  - OBJECTIVES: To assess the capability of the three-dimensional (3D) Fast Imaging
      Employing Steady-State Acquisition (FIESTA) sequence in evaluating renal artery
      stenosis (RAS). METHODS: We retrospectively analysed 79 patients referred for
      suspected RAS, examined by 3D FIESTA and contrast-enhanced magnetic resonance
      angiography (CE-MRA), using a 1.5T whole-body scanner. Image quality was assessed
      as well as the presence and grade of RAS. Patients with RAS >= 50% were evaluated
      for possible digital subtraction angiography (DSA). Sensitivity, specificity,
      negative predictive value (NPV), positive predictive value (PPV), and accuracy of
      3D FIESTA were calculated with ROC analysis using CE-MRA and DSA as the standard
      of reference. RESULTS: A total of 186 renal arteries were assessed; 36 had RAS >=
      50 % demonstrated by CE-MRA. Ten patients underwent DSA, for a total evaluation
      of 22 arteries. Sensitivity, specificity, NPV, PPV, and accuracy of 3D FIESTA
      were 91.7%, 100%, 98%, 100%, and 98%, respectively, as compared to CE-MRA, and
      88.2%, 100%, 71.4%, 100%, and 91%, respectively, as compared to DSA. The area
      under the ROC curve (AUC) of 3D FIESTA as compared to CE-MRA and DSA was 0.958
      and 0.941, respectively. CONCLUSIONS: Our study demonstrated the capability of
      the 3D FIESTA sequence in evaluating RAS, with high-quality images and good
      diagnostic accuracy. KEY POINTS: The 3D FIESTA sequence provides a robust
      evaluation of RAS. The 3D FIESTA sequence allows non-invasive evaluation of the
      renal arteries. The 3D FIESTA sequence could be a useful tool in evaluating RAS.

PMID- 25059679
TI  - Left ventricular hemodynamic changes and clinical outcomes after transcatheter
      atrial septal defect closure in adults.
AB  - OBJECTIVES: The objectives of this study are to assess current management
      algorithms for left ventricular (LV) hemodynamic and diastolic changes following
      atrial septal device occlusion in adult patients. BACKGROUND: Percutaneous
      closure is now routine for atrial septal defects (ASDs). Previous studies show
      ventricular size normalization following percutaneous closure. Case reports have
      discussed the incidence of early LV dysfunction following ASD device placement
      with some recommending delay of closure or placement of a fenestrated device in
      patients with elevated LV pressures. METHOD: All adult patients with an isolated
      secundum ASD who underwent percutaneous repair were included in this study. In
      addition to placement of the Amplatzer septal occluder, all patients had a pre
      and postprocedure transthoracic echocardiography performed measuring myocardial
      performance index (MPI). Left ventricular end diastolic pressure (LVEDP) was
      measured before and after balloon occlusion. RESULTS: Nineteen patients (17
      female and two male) were included in this study. Average age was 47.2 years (+/-
      12.7 years). All defects were of clinical significance with average Qp : Qs = 2.0
      (+/- 0.6). Balloon occlusion led to a significant (P < .01) increase in LVEDP
      (pre-LVEDP mean = 7.1 mm Hg, post-LVEDP mean = 15.3 mm Hg). There was no
      significant change in MPI. ASD device size displayed a modest correlation
      relative to the change in LVEDP (R = 0.42, P = .09). CONCLUSIONS: Percutaneous
      ASD closure induces an increase in LVEDP. Despite this, all patients tolerated
      device closure without complication. It appears safe to close ASDs in these
      patients.

PMID- 25059678
TI  - The profile of tumor antigens which can be targeted by immunotherapy depends upon
      the tumor's anatomical site.
AB  - Previously, we showed that vesicular stomatitis virus (VSV) engineered to express
      a cDNA library from human melanoma cells (ASMEL, Altered Self Melanoma Epitope
      Library) was an effective systemic therapy to treat subcutaneous (s.c.) murine
      B16 melanomas. Here, we show that intravenous treatment with the same ASMEL VSV
      cDNA library was an effective treatment for established intra-cranial (i.c.)
      melanoma brain tumors. The optimal combination of antigens identified from the
      ASMEL which treated s.c. B16 tumors (VSV-N-RAS+VSV-CYTC-C+VSV-TYRP-1) was
      ineffective against i.c. B16 brain tumors. In contrast, combination of VSV
      expressed antigens-VSV-HIF-2alpha+VSV-SOX-10+VSV-C-MYC+VSV-TYRP1-from ASMEL which
      was highly effective against i.c. B16 brain tumors, had no efficacy against the
      same tumors growing subcutaneously. Correspondingly, i.c. B16 tumors expressed a
      HIF-2alpha(Hi), SOX-10(Hi), c-myc(Hi), TYRP1, N-RAS(lo)Cytc(lo) antigen profile,
      which differed significantly from the HIF-2alpha(lo), SOX-10(lo), c-myc(lo),
      TYRP1, N-RAS(Hi)Cytc(Hi) phenotype of s.c. B16 tumors, and was imposed upon the
      tumor cells by CD11b(+) cells within the local brain tumor microenvironment.
      Combining T-cell costimulation with systemic VSV-cDNA treatment, long-term cures
      of mice with established i.c. tumors were achieved in about 75% of mice. Our data
      show that the anatomical location of a tumor profoundly affects the profile of
      antigens that it expresses. 

PMID- 25059680
TI  - Predictors of postoperative complications, prolonged length of hospital stay, and
      short-term mortality in elderly patients with malignant head and neck neoplasm.
AB  - PURPOSE: To identify and assess predictors of short-term outcomes and a prolonged
      length of hospital stay after head and neck cancer surgery in older-old and
      oldest-old patients. PROCEDURES: Patients aged >=75 years with head and neck
      cancer undergoing surgery at the Brazilian National Cancer Institute from January
      to December 2011 were assessed regarding postoperative complications, mortality,
      and length of hospital stay. RESULTS: Over the study period, 67 patients with
      head and neck cancer underwent surgery, 44.8% of whom developed complications
      within 30 days of surgery, surgical site and respiratory infections (29.9 and
      20.9%, respectively) being the most common. The mean length of hospital stay was
      7 days (range: 2-26). In multivariate analysis, previous radiotherapy, dependence
      in instrumental activities of daily living, and low serum hemoglobin (<=13.2
      g/dl) were predictors of complications. In addition, the presence of at least 1
      clinical or surgical complication, smoking, and an arm circumference <=25 cm were
      independent predictors of a prolonged length of hospital stay. CONCLUSIONS:
      Complications after head and neck cancer surgery in the elderly are common and
      related to the prolonged length of hospital stay, both being influenced by
      previous radiotherapy, smoking, functional dependence in instrumental activities
      of daily living, and nutritional conditions. Such predictors should be considered
      in a preoperative assessment of elderly patients as these are modifiable risk
      factors.

PMID- 25059681
TI  - Assessment of postpartum depressive symptoms: the importance of somatic symptoms
      and irritability.
AB  - Assessing postpartum depressive symptoms is complicated by the fact that
      irritability, fatigue, insomnia, and appetite disruptions are also related to
      normative aspects of the childbearing process. We used multigroup confirmatory
      factor analysis to compare symptoms in 271 postpartum women with those of 820 non
      postpartum women. We found that (a) irritability, insomnia, fatigue, and appetite
      loss were substantially associated with depressed mood among postpartum women
      whereas increased appetite was not; (b) irritability, insomnia, fatigue, and
      appetite changes were as strongly related to depression among postpartum women as
      they were among non-postpartum women; and (c) after controlling for overall
      depressed mood, postpartum women reported more irritability, insomnia, and
      appetite loss than the non-postpartum women. Irritability, fatigue, insomnia, and
      appetite loss are valid indicators and should be used to measure postpartum
      depressive symptoms. However, scores on these symptoms should be adjusted
      downward to account for their higher baseline rates in the postpartum population.

PMID- 25059682
TI  - The association of gender, ethnicity, age, and education with Rorschach scores.
AB  - We examined the association of gender, ethnicity, age, and education with 60
      Rorschach scores using three clinical and nonclinical samples of adults and
      youths (ns = 640, 249, and 241). As anticipated for our data sets, there were no
      reliable associations for gender, ethnicity, or adult age. However, in adults
      years of education was associated with variables indicative of complexity, the
      articulation of subtlety and nuance, cognitive synthesis, and coping resources.
      In the clinical sample of youths, increasing age was primarily associated with
      more conventional perception and less illogical thought processes. Limitations
      are discussed in conjunction with further research that could address them, along
      with implications for applied practice. 

PMID- 25059683
TI  - Social Anxiety Scale for Adolescents: factorial invariance across gender and age
      in Hispanic American adolescents.
AB  - Social anxiety is a common psychological disorder that often emerges during
      adolescence and is associated with significant impairment. Efforts to prevent
      social anxiety disorder require sound assessment measures for identifying anxious
      youth, especially those from minority backgrounds. We examined the factorial
      invariance and latent mean differences of the Social Anxiety Scale for
      Adolescents (SAS-A) across gender and age groups in Hispanic American adolescents
      (N = 1,191; 56% girls; 15-18 years) using multigroup confirmatory factor
      analyses. Results indicated that the factorial configuration of the correlated
      three-factor model of the SAS-A was invariant across gender and age. Analyses of
      latent mean differences revealed that boys exhibited higher structured means than
      girls on the Social Avoidance and Distress-General (SAD-General) subscale. On all
      SAS-A subscales, Fear of Negative Evaluation, Social Avoidance and Distress-New,
      and SAD-General, estimates of the structured means decreased with adolescent age.
      Implications for further research and clinical practice are discussed. 

PMID- 25059684
TI  - Shared decision making in chronic care in the context of evidence based practice
      in nursing.
AB  - In the decision-making environment of evidence-based practice, the following
      three sources of information must be integrated: research evidence of the
      intervention, clinical expertise, and the patient's values. In reality, evidence
      based practice usually focuses on research evidence (which may be translated into
      clinical practice guidelines) and clinical expertise without considering the
      individual patient's values. The shared decision-making model seems to be helpful
      in the integration of the individual patient's values in evidence-based practice.
      We aim to discuss the relevance of shared decision making in chronic care and to
      suggest how it can be integrated with evidence-based practice in nursing. We
      start by describing the following three possible approaches to guide the decision
      making process: the paternalistic approach, the informed approach, and the shared
      decision-making approach. Implementation of shared decision making has gained
      considerable interest in cases lacking a strong best-treatment recommendation,
      and when the available treatment options are equivalent to some extent. We
      discuss that in chronic care it is important to always invite the patient to
      participate in the decision-making process. We delineate the following six
      attributes of health care interventions in chronic care that influence the degree
      of shared decision making: the level of research evidence, the number of
      available intervention options, the burden of side effects, the impact on
      lifestyle, the patient group values, and the impact on resources. Furthermore,
      the patient's willingness to participate in shared decision making, the clinical
      expertise of the nurse, and the context in which the decision making takes place
      affect the shared decision-making process. A knowledgeable and skilled nurse with
      a positive attitude towards shared decision making-integrated with evidence-based
      practice-can facilitate the shared decision-making process. We conclude that
      nurses as well as other health care professionals in chronic care should
      integrate shared decision making with evidence-based practice to deliver patient
      centred care.

PMID- 25059685
TI  - Interaction of extracellular loop II of kappa-opioid receptor (196-228) with
      opioid peptide dynorphin in membrane environments as revealed by solid state
      nuclear magnetic resonance, quartz crystal microbalance and molecular dynamics
      simulation.
AB  - kappa-Opioid receptor is a member of the opioid receptor family and selectively
      interacts with the opioid peptide dynorphin. Extracellular loop II (ECL-II) of
      the kappa-opioid receptor displays an amphiphilic helix in membrane environments
      and the N-terminal alpha-helix of dynorphin A(1-17) (hereafter DynA17) is
      inserted into the membrane with the tilt angle of 21 degrees  to the bilayer
      normal. ECL-II peptides (1-33), corresponding to 196-228 of kappa-opioid receptor
      with [1-(13)C]- or [3-(13)C]-labeled amino acids were incorporated into large
      [dimyristoylphosphatidyl choline (DMPC)/ dihexanoylphosphatidyl choline (DHPC) =
      3, q = 3] and small bicelle (q = 1) systems. (13)C direct detection with dipolar
      decoupling and magic angle spinning (DD-MAS) nuclear magnetic resonance (NMR)
      spectra were recorded, and the (13)C chemical shift perturbation clearly
      indicated that DynA17 interacts with ECL-II at the location of Val10-Ala15.
      Quartz crystal microbalance measurements were performed to determine the binding
      constant of ECL-II with DynA17 and indicated that the binding constant between
      DynA17 and ECL-II embedded in the lipid layer was 72 times larger than that
      between DynA17 and the lipid. The result of the molecular dynamics simulation
      clearly indicates that the C-terminus of DynA17 interact with the amino acid
      residues of the region between Val10-Gln14 of ECL-II. These results suggest that
      DynA17 interacts with the ECL-II of the kappa-opioid receptor through a
      hydrophobic and short-lived electrostatic interaction with high affinity in the
      outer surface of the membrane. 

PMID- 25059686
TI  - Piezosurgery for orbital decompression surgery in thyroid associated orbitopathy.
AB  - The purpose of this study was to assess a piezosurgical device as a novel tool
      for bony orbital decompression surgery. At a multidisciplinary orbital center, 62
      surgeries were performed in 40 patients with thyroid associated orbitopathy
      (TAO). Within this retrospective case-series, we analyzed the medical records of
      these consecutive unselected patients. The reduction of proptosis was the main
      outcome measure. Indications for a two (n = 27, 44%) or three wall (35, 56%)
      decompression surgery were proptosis (n = 50 orbits, 81%) and optic neuropathy (n
      = 12, 19%). Piezosurgery enabled precise bone cuts without intraoperative
      complications. Proptosis decreased from 23.6 +/- 2.8 mm (SD) by 3 mm (95% CI: 
      3.6 to -2.5 mm) after surgery and stayed stable at 3 months (-3 mm, 95% CI: -3.61
      to -2.5 mm, p < 0.001, respectively). The effect was higher in those with
      preoperatively higher values (>24 mm versus <= 24 mm: -3.4 mm versus -2.81 mm
      before discharge from hospital and -4.1 mm versus -2.1 mm at 3 months: p < 0.001,
      respectively). After a mean long-term follow-up period of 14.6 +/- 10.4 months
      proptosis decreased by further -0.7 +/- 2.0 mm (p < 0.001). Signs of optic nerve
      compression improved after surgery. Infraorbital hypesthesia was present in 11 of
      21 (52%) orbits 3 months after surgery. The piezosurgical device is a useful tool
      for orbital decompression surgery in TAO. By cutting bone selectively, it is
      precise and reduces the invasiveness of surgery. Nevertheless, no improvement in
      outcome or reduction in morbidity over conventional techniques has been shown so
      far.

PMID- 25059687
TI  - Development and psychometric validation of the REFlective evaLuation of psoriasis
      Efficacy of Treatment and Severity (REFLETS) questionnaire: a common measure of
      plaque-type psoriasis severity and treatment efficacy for patients and
      clinicians.
AB  - BACKGROUND: To date, there is no global consensus on the definition of the
      severity of psoriasis. The REFlective evaLuation of psoriasis Efficacy of
      Treatment and Severity (REFLETS) questionnaire has recently been developed to
      provide a better understanding of plaque-type psoriasis severity and treatment
      efficacy from both patient and clinician perspectives. OBJECTIVE: This study
      aimed to develop and psychometrically validate the new REFLETS questionnaire to
      evaluate patient and clinician perceptions of plaque-type psoriasis severity and
      treatment efficacy. METHODS: Two similar versions of the REFLETS questionnaire
      were developed following a rigorous methodology for clinicians and patients,
      referring to 'the psoriasis of your patient' or to 'your psoriasis',
      respectively. An observational, longitudinal, multicentre study was conducted in
      France with 34 dermatologists and 430 mild to severe plaque-type psoriasis
      patients to finalize the questionnaire and evaluate its psychometric properties.
      RESULTS: Two dimensions were defined--severity and treatment efficacy--with three
      subdimensions within severity (impact of psoriasis, symptoms and disease course),
      and two individual items on joint pain. The questionnaire was well accepted by
      clinicians and patients. Excellent internal consistency (Cronbach's alpha = 0.66
      0.98) and test-retest reliability (intraclass correlation coefficients = 0.83
      0.94) were demonstrated. REFLETS scores were moderately to highly correlated to
      Psoriasis Area and Severity Index (r = 0.35-0.70), Skindex-29 (r = 0.46-0.82) and
      DLQI scores (r = 0.36-0.82). Patients with decreased psoriasis severity and those
      with increased treatment efficacy, according to patient global evaluations, had
      lower severity and higher treatment efficacy REFLETS scores, respectively.
      CONCLUSION: REFlective evaLuation of psoriasis Efficacy of Treatment and Severity
      is a promising tool for assessing plaque-type psoriasis severity and treatment
      efficacy from patient and clinician perspectives. It may help to improve patient
      and clinician communication in treatment decision making.

PMID- 25059688
TI  - RNA-seq of the aging brain in the short-lived fish N. furzeri - conserved
      pathways and novel genes associated with neurogenesis.
AB  - The brains of teleost fish show extensive adult neurogenesis and neuronal
      regeneration. The patterns of gene regulation during fish brain aging are
      unknown. The short-lived teleost fish Nothobranchius furzeri shows markers of
      brain aging including reduced learning performances, gliosis, and reduced adult
      neurogenesis. We used RNA-seq to quantify genome-wide transcript regulation and
      sampled five different time points to characterize whole-genome transcript
      regulation during brain aging of N. furzeri. Comparison with human datasets
      revealed conserved up-regulation of ribosome, lysosome, and complement activation
      and conserved down-regulation of synapse, mitochondrion, proteasome, and
      spliceosome. Down-regulated genes differ in their temporal profiles: neurogenesis
      and extracellular matrix genes showed rapid decay, synaptic and axonal genes a
      progressive decay. A substantial proportion of differentially expressed genes
      (~40%) showed inversion of their temporal profiles in the last time point:
      spliceosome and proteasome showed initial down-regulation and stress-response
      genes initial up-regulation. Extensive regulation was detected for chromatin
      remodelers of the DNMT and CBX families as well as members of the polycomb
      complex and was mirrored by an up-regulation of the H3K27me3 epigenetic mark.
      Network analysis showed extensive coregulation of cell cycle/DNA synthesis genes
      with the uncharacterized zinc-finger protein ZNF367 as central hub. In situ
      hybridization showed that ZNF367 is expressed in neuronal stem cell niches of
      both embryonic zebrafish and adult N. furzeri. Other genes down-regulated with
      age, not previously associated with adult neurogenesis and with similar patterns
      of expression are AGR2, DNMT3A, KRCP, MEX3A, SCML4, and CBX1. CBX7, on the other
      hand, was up-regulated with age. 

PMID- 25059689
TI  - A prospective study of the introduction of complementary foods in contemporary
      Australian infants: What, when and why?
AB  - AIM: To accurately establish the extent to which breastfeeding exclusivity and
      duration and the introduction of foods other than breast milk are congruous with
      Australian infant feeding guidelines among a cohort of primiparous women and
      their infants in Australia. METHOD: The Feeding Queensland Babies Study is
      primarily a questionnaire-based prospective birth cohort study of infant feeding
      attitudes and behaviours but also collected significant data on feeding patterns
      in infancy. These data were extracted from the demographic questionnaire and from
      questionnaires administered at 4 and 6 months of infant age. Participants were
      healthy primiparous Australian women aged between 18 and 40 years, recruited by
      convenience sampling in Queensland, Australia. Data were collected by self
      administered questionnaire both online and on paper between October 2010 and
      September 2011. RESULTS: Breastfeeding initiation in this cohort is high;
      however, by 4 months of age, 15.4% of mothers had completely ceased any
      breastfeeding, 28.7% of infants had been given formula and 18.5% had been
      introduced to baby cereal. By 6 months of age, 98.4% of infants had been
      introduced to non-milk foods, most commonly at a rate of one new food every 4 to
      5 days. CONCLUSION: Contemporary prospective data on infant feeding have value in
      describing trends that may influence the health outcomes of a generation of
      Australian children. Even in this group of relatively well-educated Australian
      women, premature cessation of breastfeeding and the early introduction of foods
      other than breast milk to infants demonstrate behaviours not congruous with
      evidence-based guidelines.

PMID- 25059690
TI  - Quality of life after volar locked plating: a 10-year follow-up study of patients
      with intra-articular distal radius fractures.
AB  - BACKGROUND: This study aimed to present functional results and patient's health
      related quality of life (HRQOL) data ten years after volar locked plate fixation
      (VPF) of unstable intra-articular distal radial fractures (DRF). METHODS: Thirty
      nine patients with a mean age of sixty-one years were operatively treated with
      VPF after intra-articular distal radial fractures. They were evaluated two, six,
      and ten years postoperatively according to the Gartland and Werley score. For
      subjective evaluation the Short Form 36 (SF-36) and the Disability of Arm,
      Shoulder and Hand (DASH) questionnaires were adopted. RESULTS: Overall, wrist
      function did not differ significantly two, six and ten years after the operation.
      Over 90% patients achieved "good" or "excellent" results ten years after surgery
      according to the Gartland and Werley score. Ten years postoperatively the results
      of the SF 36 did not differ significantly from the two- and six-year follow-up.
      Overall findings from the SF-36 did not differ significantly from the data of
      Austrian and American norm populations. Only in the subscale of mental health
      (MH) the ten-year follow-up did show significantly poorer results (p = 0.045)
      compared to the Austrian norm population. The median DASH scores did not show
      significant differences during the ten-year follow-up period. CONCLUSION: The ten
      year results of this single-center study suggest that operative treatment of
      intra-articular DRF with volar locked plates is a useful and satisfactory therapy
      option, both in terms of function and HRQOL.

PMID- 25059691
TI  - Early identification and management of chronic kidney disease in adults: summary
      of updated NICE guidance.

PMID- 25059693
TI  - Interobserver agreement in the interpretation of outpatient head CT scans in an
      academic neuroradiology practice.
AB  - BACKGROUND AND PURPOSE: The repeatability of head CT interpretations may be
      studied in different contexts: in peer-review quality assurance interventions or
      in interobserver agreement studies. We assessed the agreement between double
      blind reports of outpatient CT scans in a routine academic practice. MATERIALS
      AND METHODS: Outpatient head CT scans (119 patients) were randomly selected to be
      read twice in a blinded fashion by 8 neuroradiologists practicing in an academic
      institution during 1 year. Nonstandardized reports were analyzed to extract 4
      items (answer to the clinical question, major findings, incidental findings,
      recommendations for further investigations) from each report, to identify
      agreement or discrepancies (classified as class 2 [mentioned or not mentioned or
      contradictions between reports], class 1 [mentioned in both reports but diverging
      in location or severity], 0 [concordant], or not applicable), according to a
      standardized data-extraction form. Agreement regarding the presence or absence of
      clinically significant or incidental findings was studied with kappa statistics.
      RESULTS: The interobserver agreement regarding head CT studies with positive and
      negative results for clinically pertinent findings was 0.86 (0.77-0.95), but
      concordance was only 75.6% (67.2%-82.5%). Class 2 discrepancy was found in 15.1%;
      class 1 discrepancy, in 9.2% of cases. The kappa value for reporting incidental
      findings was 0.59 (0.45-0.74), with class 2 discrepancy in 29.4% of cases. Most
      discrepancies did not impact the clinical management of patients. CONCLUSIONS:
      Discrepancies in double-blind interpretations of head CT examinations were more
      common than reported in peer-review quality assurance programs.

PMID- 25059694
TI  - Treatment of poor-grade subarachnoid hemorrhage trial.
AB  - BACKGROUND AND PURPOSE: Management of poor-grade subarachnoid hemorrhage is based
      on limited evidence from small single-center retrospective observational studies.
      The purpose of this study was to undertake a single-center randomized controlled
      feasibility trial comparing a strategy of early endovascular aneurysm treatment
      with treatment after neurologic recovery in this group of patients. MATERIALS AND
      METHODS: Patients with poor-grade SAH were randomized within 24 hours of
      admission to early treatment or treatment after neurologic recovery. If a patient
      was randomized to early treatment, the aneurysm was treated endovascularly within
      24 hours of randomization. Recruitment rate, safety profile, and functional
      outcome at the time of discharge and at 6 months were assessed. RESULTS: Fourteen
      of 51 patients screened were eligible for the trial. Of these 14, 8 patients were
      randomized (57%). All patients in the early coiling arm received treatment within
      24 hours of randomization. There was no treatment-related complication. Overall,
      good outcome occurred in 25% of patients; the mortality rate was 75%. Patients in
      the early treatment arm (n = 5) had a good outcome rate of 20%, while those in
      treatment after neurologic recovery arm (n = 3) had a good outcome rate of 33.3%.
      CONCLUSIONS: This was a feasibility study that demonstrated that recruitment and
      randomization for comparing management strategies in poor-grade SAH are feasible.
      The recruitment rate among eligible patients was encouraging (57%), though a
      number of patients had to be excluded due to ineligibility. A multicenter study
      is necessary to recruit the numbers required to compare the clinical outcomes of
      these management strategies.

PMID- 25059695
TI  - Cement salvage of instrumentation-associated vertebral fractures.
AB  - BACKGROUND AND PURPOSE: Spinal instrumentation plays a key role in the treatment
      of spinal instability in patients with metastatic tumors. Poor bone quality,
      radiation, and diffuse osseous tumor involvement present significant challenges
      to spinal stabilization with instrumentation and occasionally result in
      postinstrumentation compression fractures. Vertebral cement augmentation has been
      effective in the treatment of painful tumor-related compression fractures. Our
      objective was to describe cement augmentation options in the treatment of
      vertebral compression fractures associated with spinal instrumentation in
      patients with metastatic tumors. MATERIALS AND METHODS: Patients who underwent
      percutaneous vertebral cement augmentation in the treatment of instrumentation
      associated vertebral compression fractures between 2005 and 2011 were included in
      the analysis. Only fractures that occurred within the construct or at an adjacent
      level were included. The change in Visual Analog Scale and need for further
      surgery were analyzed. RESULTS: Eleven patients met the inclusion criteria, with
      8 tumors located in the thoracic spine and 3 tumors in the lumbar spine. The
      median time between instrumented surgery and vertebral augmentation was 5 months
      (1-48 months) and the median follow-up after cement augmentation was 24 months (4
      59 months). A total of 22 vertebrae that were either within or immediately
      adjacent to the surgical instrumentation underwent vertebral augmentation. All
      patients reported a decrease in their pain scores (mean decrease: 6 Visual Analog
      Scale points; P < .003). One patient required reoperation after cement
      augmentation. None of the patients experienced vertebral cement augmentation
      related complications. CONCLUSIONS: Vertebral cement augmentation represents a
      safe and effective treatment option in patients with recurrent or progressive
      back pain and instrumentation-associated vertebral compression fractures.

PMID- 25059696
TI  - 3T intraoperative MRI for management of pediatric CNS neoplasms.
AB  - BACKGROUND AND PURPOSE: High-field-strength intraoperative MR imaging has emerged
      as a powerful adjunct for resection of brain tumors. However, its exact role has
      not been firmly established. We sought to determine the impact of 3T
      intraoperative MRI on the surgical management of childhood CNS tumors. MATERIALS
      AND METHODS: We evaluated patient data from a single academic children's hospital
      during a consecutive 24-month period after installation of a 3T-intraoperative
      MRI. Tumor location, histology, surgical approach, operating room time, presence
      and volume of residual tumor, need for tumor and non-tumor-related reoperation,
      and anesthesia- and MR imaging-related complications were evaluated. Comparison
      with pre-intraoperative MRI controls was performed. RESULTS: One hundred ninety
      four patients underwent intraoperative MRI-guided surgery. Of these, 168 were 18
      years or younger (mean, 8.9 +/- 5.0 years; 108 males/60 females). There were 65
      posterior fossa tumors. The most common tumors were pilocytic astrocytoma (n =
      31, 19%), low-grade glioma (n = 31, 19%), and medulloblastoma (n = 20, 12%). An
      average of 1.2 scanning sessions was performed per patient (maximum, 3). There
      were no MR imaging-related safety issues. Additional tumor was resected after
      scanning in 21% of patients. Among patients with a preoperative goal of gross
      total resection, 93% achieved this goal. The 30-day reoperation rate was <1% (n =
      1), and no patient required additional postoperative MR imaging during the same
      hospital stay. CONCLUSIONS: Intraoperative MRI is safe and increases the
      likelihood of gross total resection, albeit with increased operating room time,
      and reduces the need for early reoperation or repeat sedation for postoperative
      scans in children with brain tumors.

PMID- 25059697
TI  - Adding value to health care: where radiologists may contribute.

PMID- 25059698
TI  - Transcranial sonography of the substantia nigra: digital image analysis.
AB  - BACKGROUND AND PURPOSE: Increased echogenicity of the substantia nigra is a
      typical transcranial sonography finding in Parkinson disease. Experimental
      software for digital analysis of the echogenic substantia nigra area has been
      developed. The aim of this study was to compare the evaluation of substantia
      nigra echogenicity by using digital analysis with a manual measurement in
      patients with Parkinson disease and healthy volunteers. MATERIALS AND METHODS:
      One hundred thirteen healthy volunteers were enrolled in the derivation cohort,
      and 50 healthy volunteers and 30 patients with Parkinson disease, in the
      validation cohort. The substantia nigra was imaged from the right and left
      temporal bone window by using transcranial sonography. All subjects were examined
      twice by using different sonographic machines by an experienced sonographer.
      DICOM images of the substantia nigra were encoded; then, digital analysis and
      manual measurement of the substantia nigra were performed. The 90th percentile of
      the derivation cohort values was used as a cut-point for the evaluation of the
      hyperechogenic substantia nigra in the validation cohort. The Spearman
      coefficient was used for assessment of the correlation between both measurements.
      The Cohen kappa coefficient was used for the assessment of the correlation
      between both measurements and Parkinson disease diagnosis. RESULTS: The Spearman
      coefficient between measurements by using different machines was 0.686 for
      digital analysis and 0.721 for manual measurement (P < .0001). Hyperechogenic
      substantia nigra was detected in the same 26 (86.7%) patients with Parkinson
      disease by using both measurements. Cohen kappa coefficients for digital analysis
      and manual measurement were 0.787 and 0.762, respectively (P < .0001).
      CONCLUSIONS: The present study showed comparable results when measuring the
      substantia nigra features conventionally and by using the developed software.

PMID- 25059699
TI  - Early reperfusion rates with IV tPA are determined by CTA clot characteristics.
AB  - BACKGROUND AND PURPOSE: An ability to predict early reperfusion with IV tPA in
      patients with acute ischemic stroke and intracranial clots can help clinicians
      decide if additional intra-arterial therapy is needed or not. We explored the
      association between novel clot characteristics on baseline CTA and early
      reperfusion with IV tPA in patients with acute ischemic stroke by using
      classification and regression tree analysis. MATERIALS AND METHODS: Data are from
      patients with acute ischemic stroke and proximal anterior circulation occlusions
      from the Calgary CTA data base (2003-2012) and the Keimyung Stroke Registry (2005
      2009). Patients receiving IV tPA followed by intra-arterial therapy were
      included. Clot location, length, residual flow within the clot, ratio of contrast
      Hounsfield units pre- and postclot, and the M1 segment origin to the proximal
      clot interface distance were assessed on baseline CTA. Early reperfusion (TICI 2a
      and above) with IV tPA was assessed on the first angiogram. RESULTS: Two hundred
      twenty-eight patients (50.4% men; median age, 69 years; median baseline NIHSS
      score, 17) fulfilled the inclusion criteria. Median symptom onset to IV tPA time
      was 120 minutes (interquartile range = 70 minutes); median IV tPA to first
      angiography time was 70.5 minutes (interquartile range = 62 minutes). Patients
      with residual flow within the clot were 5 times more likely to reperfuse than
      those without it. Patients with residual flow and a shorter clot length (<=15 mm)
      were most likely to reperfuse (70.6%). Patients with clots in the M1 MCA without
      residual flow reperfused more if clots were distal and had a clot interface ratio
      in Hounsfield units of <2 (36.8%). Patients with proximal M1 clots without
      residual flow reperfused 8% of the time. Carotid-T/-L occlusions rarely
      reperfused (1.7%). Interrater reliability for these clot characteristics was
      good. CONCLUSIONS: Our study shows that clot characteristics on CTA help
      physicians estimate a range of early reperfusion rates with IV tPA.

PMID- 25059700
TI  - "Y" and "X" stent-assisted coiling of complex and wide-neck intracranial
      bifurcation aneurysms.
AB  - BACKGROUND AND PURPOSE: Stent-assisted coiling with two stents has been described
      in some series for the treatment of complex and wide-neck bifurcation aneurysms.
      Our aim was to report our experience of a stent-assisted coiling technique with
      double stents in "Y" and "X" configurations, with emphasis on safety,
      feasibility, and efficacy. MATERIALS AND METHODS: Clinical and angiographic
      outcomes of patients for whom the strategic therapeutic option was the stent
      assisted coiling technique in a Y or X configuration for neck scaffolding from
      June 2006 to June 2013 were retrospectively analyzed. RESULTS: One hundred five
      aneurysms in 97 patients were treated during 100 consecutive procedures. There
      were 54.2% (57/105) MCA, 28.6% (30/105) anterior communicating artery, 16.2%
      (17/105) basilar tip, and 1.0% (1/105) ICA termination aneurysms. A Y stent
      placement was used to treat 87 aneurysms in 85 procedures; an X stent placement
      was used to treat 7 aneurysms in 6 procedures, while 9 procedures failed for 11
      aneurysms. There were 10.0% (10/100) procedure-related permanent neurologic
      deficits and 1.0% (1/100) death. The immediate angiographic controls showed a
      complete occlusion in 47.6% (50/105) of the aneurysms and a partial (neck or sac
      remnant) occlusion in 52.4% (55/105). To date, 81.0% (85/105) of the aneurysms
      have been followed up (mean, 17 months) with angiography, disclosing a
      recanalization in 5.9% (5/85) and an improvement in 42.4% (36/85). At discharge
      and follow-up, the mRS score was 0 in 83.5% (81/97) of patients, 1 in 4.1%
      (4/97), 2 in 3.1% (3/97), 3 in 4.1% (4/97), 4 in 3.1% (3/97), and 6 in 2.1%
      (2/97). CONCLUSIONS: Y and X stent-assisted coiling of complex and wide-neck
      intracranial bifurcation aneurysms is an effective technique.

PMID- 25059701
TI  - Effect of the CT table strap on radiation exposure and image quality during
      cervical spine CT.
AB  - BACKGROUND AND PURPOSE: The CT table strap may impair shoulder lowering during
      cervical spine CT. The purpose of this investigation was to evaluate the effect
      of the CT table strap on radiation exposure and image quality during CT of the
      cervical spine. MATERIALS AND METHODS: Patients undergoing cervical spine CT were
      prospectively randomized to having the CT table strap placed around the torso and
      arms (control group) or around the torso only (intervention group). Radiation
      exposure, shoulder position, and image quality were evaluated. Potential
      confounders, including neck diameter and scan length, were also assessed.
      RESULTS: Fifty-eight patients were enrolled and randomized, and 51 subjects were
      included in the final study population. There was a 21% decrease in radiation
      exposure in the intervention group compared with the control group (mean dose
      length product, 540 +/- 152 versus 686 +/- 200 mGy * cm, P = .005). Subjects in
      the intervention group achieved shoulder lowering of an average of >1 vertebral
      body lower than the control group (mean shoulder level, 7.7 +/- 1.3 versus 6.5 +/
      1.3, P = .001). Subjective image quality, determined by the lowest level of
      spinal cord visibility, was also better in the intervention group (mean cord
      visibility level, 6.9 +/- 1.3 versus 5.9 +/- 1.3, P = .006). No differences in
      neck diameter (P = .28) or scan length (P = .55) were observed between groups.
      CONCLUSIONS: The CT table strap inhibits shoulder lowering during CT of the
      cervical spine. Placement of the patient's arms outside the CT table strap
      results in decreased radiation exposure and increased image quality compared with
      patients whose arms are placed inside the strap.

PMID- 25059702
TI  - The financial crisis, health and health inequities in Europe: the need for
      regulations, redistribution and social protection.
AB  - In 2009, Europe was hit by one of the worst debt crises in history. Although the
      Eurozone crisis is often depicted as an effect of government mismanagement and
      corruption, it was a consequence of the 2008 U.S. banking crisis which was caused
      by more than three decades of neoliberal policies, financial deregulation and
      widening economic inequities.Evidence indicates that the Eurozone crisis
      disproportionately affected vulnerable populations in society and caused sharp
      increases of suicides and deaths due to mental and behavioral disorders
      especially among those who lost their jobs, houses and economic activities
      because of the crisis. Although little research has, so far, studied the effects
      of the crisis on health inequities, evidence showed that the 2009 economic
      downturn increased the number of people living in poverty and widened income
      inequality especially in European countries severely hit by the debt crisis.
      Data, however, also suggest favorable health trends and a reduction of traffic
      deaths fatalities in the general population during the economic recession.
      Moreover, egalitarian policies protecting the most disadvantaged populations with
      strong social protections proved to be effective in decoupling the link between
      job losses and suicides.Unfortunately, policy responses after the crisis in most
      European countries have mainly consisted in bank bailouts and austerity programs.
      These reforms have not only exacerbated the debt crisis and widened inequities in
      wealth but also failed to address the root causes of the crisis. In order to
      prevent a future financial downturn and promote a more equitable and sustainable
      society, European governments and international institutions need to adopt new
      regulations of banking and finance as well as policies of economic redistribution
      and investment in social protection. These policy changes, however, require the
      abandonment of the neoliberal ideology to craft a new global political economy
      where markets and gross domestic product (GDP) are no longer the main national
      policy goals, but just means to human and health improvements. 

PMID- 25059703
TI  - Retrospective cohort study evaluating exenatide twice daily and long-acting
      insulin analogs in a Veterans Health Administration population with type 2
      diabetes.
AB  - AIM: This was a retrospective cohort study that evaluated the differences in
      glycated haemoglobin (HbA1c) and body mass index (BMI) in veterans with type 2
      diabetes mellitus (T2DM), prescribed exenatide twice daily (BID) versus long
      acting insulin analog (LAIA) two years after initiation in the United States (US)
      veteran population. MATERIALS AND METHODS: Patients were included if they were >=
      18 years old with T2DM, and initiated exenatide BID or LAIA at the Veterans
      Health Administration between January 1, 2006 and December 31, 2010. Multivariate
      models were used to evaluate the changes in HbA1c and BMI between groups,
      controlling for potential confounders. Logistic regression was used to evaluate
      the odds of achieving >= 0.5% HbA1c reduction based on baseline HbA1c
      stratifications: low,<7%; moderate, 7% to<9%; and high,>= 9%. RESULTS: A total of
      446 exenatide BID and 51,531 LAIA patients met inclusion/exclusion criteria. On
      average, exenatide BID patients were significantly older (64 versus 60 years)
      with a higher BMI (37.8 versus 32.9 kg/m(2)). Baseline HbA1c was 8.2% and 8.8%
      for exenatide BID and LAIA patients, respectively (P<0.001); otherwise, patients
      were similar for all other characteristics. Exenatide BID treatment was
      significantly associated with a 0.32% (95%CI: 0.18-0.47%) greater reduction in
      HbA1c at two years compared with LAIA. Similar findings were observed for BMI
      reduction (0.68 kg/m(2); 95%CI: 0.42-0.95 kg/m(2)). Exenatide BID patients with
      moderate baseline HbA1c had significantly higher odds of achieving >= 0.5% HbA1c
      reduction compared with LAIA patients (OR=1.5; 95%CI: 1.2-2.0). CONCLUSIONS:
      Veterans treated with exenatide BID had significantly greater reduction in HbA1c
      and BMI compared with patients treated with LAIA patients two years after
      initiation.

PMID- 25059704
TI  - A Hunter Patient with a Severe Phenotype Reveals Two Large Deletions and Two
      Duplications Extending 1.2 Mb Distally to IDS Locus.
AB  - Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is an X-linked lysosomal
      storage disorder caused by the deficit of iduronate 2-sulfatase (IDS), an enzyme
      involved in the glycosaminoglycans (GAGs) degradation. We here report the case of
      a 9-year-old boy who was diagnosed with an extremely severe form of MPS II at 10
      months of age. Sequencing of the IDS gene revealed the deletion of exons 1-7,
      extending distally and removing the entire pseudogene IDSP1. The difficulty to
      define the boundaries of the deletion and the particular severity of the patient
      phenotype suggested to verify the presence of pathological copy number variations
      (CNVs) in the genome, by the array CGH (aCGH) technology. The examination
      revealed the presence of two deletions alternate with two duplications, overall
      affecting a region of about 1.2 Mb distally to IDS gene. This is the first
      complex rearrangement involving IDS and extending to a large region located
      distally to it described in a severe Hunter patient, as evidenced by the CNVs
      databases interrogated. The analysis of the genes involved in the rearrangement
      and of the disorders correlated with them did not help to clarify the phenotype
      observed in our patient, except for the deletion of the IDS gene, which explains
      per se the Hunter phenotype. However, this cannot exclude a potential "contiguous
      gene syndrome" as well as the future rising of additional pathological symptoms
      associated with the other extra genes involved in the identified rearrangement. 

PMID- 25059705
TI  - Mycoplasma detection and isolation from one-humped camels (Camelus dromedarius).
AB  - In scientific literature, a small amount of information is found concerning
      mycoplasmosis in camel species. Mycoplasma (M.) arginini, Acholeplasma (A.)
      laidlawii, and Acholeplasma oculi have been reported to be isolated from these
      host species. Serologically positive results have been reported for Mycoplasma
      mycoides subsp. mycoides SC type, Mycoplasma capricolum subsp. capripneumoniae,
      and M. mycoides subsp. capri. The aims of this study were to detect, isolate, and
      identify mycoplasmas from camels (Camelus dromedarius). Initially, saliva and ear
      smears plus conjunctival and vaginal secretions were taken from five female
      animals, but only conjunctival secretions in three male animals, all belonging to
      the same farm. An unknown mycoplasma was isolated from one of the vagina samples.
      Additionally, another unknown and uncultured mycoplasma was detected with
      molecular biology in the same sample. In the second stage, 23 vaginal secretions
      were taken from the same farm plus another secretion from a different one. Ten
      isolates of the same unknown and previously isolated mycoplasma were detected,
      nine of them recovered from the vagina of female camels. Some mycoplasmas have
      been related to reproductive disorders; however, there is no evidence that the
      isolated mycoplasmas are related to such disorders. 

PMID- 25059706
TI  - Chlorophyll degradation: the tocopherol biosynthesis-related phytol hydrolase in
      Arabidopsis seeds is still missing.
AB  - Phytyl diphosphate (PDP) is the prenyl precursor for tocopherol biosynthesis.
      Based on recent genetic evidence, PDP is supplied to the tocopherol biosynthetic
      pathway primarily by chlorophyll degradation and sequential phytol
      phosphorylation. Three enzymes of Arabidopsis (Arabidopsis thaliana) are known to
      be capable of removing the phytol chain from chlorophyll in vitro:
      chlorophyllase1 (CLH1), CLH2, and pheophytin pheophorbide hydrolase (PPH), which
      specifically hydrolyzes pheophytin. While PPH, but not chlorophyllases, is
      required for in vivo chlorophyll breakdown during Arabidopsis leaf senescence,
      little is known about the involvement of these phytol-releasing enzymes in
      tocopherol biosynthesis. To explore the origin of PDP for tocopherol synthesis,
      seed tocopherol concentrations were determined in Arabidopsis lines engineered
      for seed-specific overexpression of PPH and in single and multiple mutants in the
      three genes encoding known dephytylating enzymes. Except for modestly increasing
      tocopherol content observed in the PPH overexpressor, none of the remaining lines
      exhibited significantly reduced tocopherol concentrations, suggesting that the
      known chlorophyll-derived phytol-releasing enzymes do not play major roles in
      tocopherol biosynthesis. Tocopherol content of seeds from double mutants in
      NONYELLOWING1 (NYE1) and NYE2, regulators of chlorophyll degradation, had modest
      reduction compared with wild-type seeds, although mature seeds of the double
      mutant retained significantly higher chlorophyll levels. These findings suggest
      that NYEs may play limited roles in regulating an unknown tocopherol biosynthesis
      related phytol hydrolase. Meanwhile, seeds of wild-type over-expressing NYE1 had
      lower tocopherol levels, suggesting that phytol derived from NYE1-dependent
      chlorophyll degradation probably doesn't enter tocopherol biosynthesis. Potential
      routes of chlorophyll degradation are discussed in relation to tocopherol
      biosynthesis. 

PMID- 25059707
TI  - Auxin and strigolactone signaling are required for modulation of Arabidopsis
      shoot branching by nitrogen supply.
AB  - The degree of shoot branching is strongly affected by environmental conditions,
      such as nutrient availability. Here we demonstrate that nitrate limitation
      reduces shoot branching in Arabidopsis (Arabidopsis thaliana) both by delaying
      axillary bud activation and by attenuating the basipetal sequence of bud
      activation that is triggered following floral transition. Ammonium supply has
      similar effects, suggesting that they are caused by plant nitrogen (N) status,
      rather than direct nitrate signaling. We identify increased auxin export from
      active shoot apices, resulting in increased auxin in the polar auxin transport
      stream of the main stem, as a likely cause for the suppression of basal branches.
      Consistent with this idea, in the auxin response mutant axr1 and the
      strigolactone biosynthesis mutant more axillary growth1, increased retention of
      basal branches on low N is associated with a failure to increase auxin in the
      main stem. The complex interactions between the hormones that regulate branching
      make it difficult to rule out other mechanisms of N action, such as up-regulation
      of strigolactone synthesis. However, the proposed increase in auxin export from
      active buds can also explain how reduced shoot branching is achieved without
      compromising root growth, leading to the characteristic shift in relative biomass
      allocation to the root when N is limiting. 

PMID- 25059708
TI  - Functional soil microbiome: belowground solutions to an aboveground problem.
AB  - There is considerable evidence in the literature that beneficial rhizospheric
      microbes can alter plant morphology, enhance plant growth, and increase mineral
      content. Of late, there is a surge to understand the impact of the microbiome on
      plant health. Recent research shows the utilization of novel sequencing
      techniques to identify the microbiome in model systems such as Arabidopsis
      (Arabidopsis thaliana) and maize (Zea mays). However, it is not known how the
      community of microbes identified may play a role to improve plant health and
      fitness. There are very few detailed studies with isolated beneficial microbes
      showing the importance of the functional microbiome in plant fitness and disease
      protection. Some recent work on the cultivated microbiome in rice (Oryza sativa)
      shows that a wide diversity of bacterial species is associated with the roots of
      field-grown rice plants. However, the biological significance and potential
      effects of the microbiome on the host plants are completely unknown. Work
      performed with isolated strains showed various genetic pathways that are involved
      in the recognition of host-specific factors that play roles in beneficial host
      microbe interactions. The composition of the microbiome in plants is dynamic and
      controlled by multiple factors. In the case of the rhizosphere, temperature, pH,
      and the presence of chemical signals from bacteria, plants, and nematodes all
      shape the environment and influence which organisms will flourish. This provides
      a basis for plants and their microbiomes to selectively associate with one
      another. This Update addresses the importance of the functional microbiome to
      identify phenotypes that may provide a sustainable and effective strategy to
      increase crop yield and food security. 

PMID- 25059709
TI  - Demographic events and evolutionary forces shaping European genetic diversity.
AB  - Europeans have been the focus of some of the largest studies of genetic diversity
      in any species to date. Recent genome-wide data have reinforced the hypothesis
      that present-day European genetic diversity is strongly correlated with
      geography. The remaining challenge now is to understand more precisely how
      patterns of diversity in Europe reflect ancient demographic events such as
      postglacial expansions or the spread of farming. It is likely that recent
      advances in paleogenetics will give us some of these answers. There has also been
      progress in identifying specific segments of European genomes that reflect
      adaptations to selective pressures from the physical environment, disease, and
      dietary shifts. A growing understanding of how modern European genetic diversity
      has been shaped by demographic and evolutionary forces is not only of basic
      historical and anthropological interest but also aids genetic studies of disease.

PMID- 25059710
TI  - Specialists and generalists: the sexual ecology of the genome.
AB  - Sexual antagonism occurs when an allele is beneficial in one sex but costly in
      the other. Parental antagonism occurs when an allele is beneficial when inherited
      from one sex but costly when inherited from the other because of fitness
      interactions among kin. Sexual and parental antagonisms together define four
      genetic niches within the genome that favor different patterns of gene
      expression. Natural selection generates linkage disequilibrium among sexually and
      parentally antagonistic loci with male-beneficial alleles coupled to alleles that
      are beneficial when inherited from males and female-beneficial alleles coupled to
      alleles that are beneficial when inherited from females. Linkage disequilibrium
      also develops between sexually and parentally antagonistic loci and loci that
      influence sex determination. Genes evolve sex-specific expression to resolve
      sexual antagonism and evolve imprinted expression to resolve parental antagonism.
      Sex-specific chromosomes allow a gene to specialize in a single niche. 

PMID- 25059711
TI  - Two-dimensional strain and strain rate imaging of the left atrium and left
      ventricle in adult patients with atrial septal defects before and after the later
      stage of percutaneous device closure.
AB  - AIM: Atrial septal defect (ASD) causes chronic volume overload of the right
      heart. The potential adverse effects of this long-standing volume overload to
      left atrium (LA) and left ventricle (LV) and their response to ASD closure has
      been poorly studied. METHODS: We studied 20 ASD patients before the procedure, at
      the 24-hour and 1 month following the percutaneous closure. Twenty age-matched
      controls served as the control group. The analysis for atrial deformation was
      performed on the lateral wall, mid segment of the LA from apical four-chamber
      view. Peak longitudinal strain (S) and strain rate (SR) during LA reservoir,
      passive emptying, atrial contraction phases and LV global longitudinal systolic S
      and SR were measured. RESULTS: Peak S and SR at LA reservoir, conduit and late
      contraction phases in ASD patients were similar to controls. All of these
      parameters increased immediately after the closure of the defect. Similarly, SLV
      and SRLV in ASD patients were not significantly different from the controls and
      significantly increased after the closure. But LA S, SR and LV S, SR results
      decreased in 1 month after the closure. SLV in ASD patients was significantly
      correlated with echocardiographic findings and the invasively measured defect
      size. CONCLUSION: LA and LV S and SR are not significantly affected in ASD
      patients. However, correction of the long-standing volume overload by
      percutaneous closure causes an early increase in LA and LV longitudinal
      deformation that correlates with the magnitude of the atrial septal defect. But
      this increase decreased in 1 month after closure.

PMID- 25059712
TI  - A comparative study of the diagnostic accuracy of cone beam computed tomography
      and intraoral radiographic modalities for the detection of noncavitated caries.
AB  - OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of
      cone beam computed tomography (CBCT) in the detection of approximal and occlusal
      noncavitated carious lesions. METHODS: A total of 135 extracted human posterior
      teeth were used. They were radiographed using the following: conventional film
      (Kodak Insight), a digital system (PSP plates Digora Optime, Soredex), and a CBCT
      system (NewTom 3G, Quantitative Radiology). All the images were assessed by two
      independent observers twice. Receiver operating characteristic analysis (Az) was
      used. RESULTS: NewTom 3G 9" CBCT was statistically inferior to conventional film
      and a digital system for the detection of approximal caries. NewTom 3G 9" had
      significantly higher Az values than PSP plate (p < 0.05), but there were no
      statistically significant differences between the Az values for CBCT and film (p
      > 0.33) for occlusal surface caries. CONCLUSION: The diagnostic accuracy of all
      three tested radiographic systems is low, and it is necessary to use other
      methods to improve early caries detection. CLINICAL RELEVANCE: CBCT has found a
      wide application in different fields of dentistry. The report from a CBCT
      examination performed for any of these reasons should include all abnormal
      findings, and the detection of noncavitated caries lesions is especially
      important because it facilitates the use of noninvasive treatment.

PMID- 25059713
TI  - Optical nonlinearity in Cu2CdSnS4 and alpha/beta-Cu2ZnSiS4: diamond-like
      semiconductors with high laser-damage thresholds.
AB  - Cu2CdSnS4 and alpha/beta-Cu2ZnSiS4 meet several criteria for promising nonlinear
      optical materials for use in the infrared (IR) region. Both are air-stable,
      crystallize in noncentrosymmetric space groups, and possess high thermal
      stabilities. Cu2CdSnS4 and alpha/beta-Cu2ZnSiS4 display wide ranges of optical
      transparency, 1.4-25 and 0.7-25 MUm, respectively, and have relatively large
      second-order nonlinearity as well as phase matchability for wide regions in the
      IR. The laser-damage threshold (LDT) for Cu2CdSnS4 is 0.2 GW/cm(2), whereas
      alpha/beta-Cu2ZnSiS4 has a LDT of 2.0 GW/cm(2) for picosecond near-IR excitation.
      Both compounds also exhibit efficient third-order nonlinearity. Electronic
      structure calculations provide insight into the variation in properties. 

PMID- 25059715
TI  - "Case finding" in dementia is simply screening with no evidence of benefit.

PMID- 25059714
TI  - The meningococcal autotransporter AutA is implicated in autoaggregation and
      biofilm formation.
AB  - Autotransporters (ATs) are proteins secreted by Gram-negative bacteria that often
      play a role in virulence. Eight different ATs have been identified in Neisseria
      meningitidis, but only six of them have been characterized. AutA is one of the
      remaining ATs. Its expression remains controversial. Here, we show that the autA
      gene is present in many neisserial species, but its expression is often disrupted
      by various genetic features; however, it is expressed in certain strains of N.
      meningitidis. By sequencing the autA gene in large panels of disease isolates and
      Western blot analysis, we demonstrated that AutA expression is prone to phase
      variation at AAGC nucleotide repeats located within the DNA encoding the signal
      sequence. AutA is not secreted into the extracellular medium, but remains
      associated with the bacterial cell surface. We further demonstrate that AutA
      expression induces autoaggregation in a process that, dependent on the particular
      strain, may require extracellular DNA (eDNA). This property influences the
      organization of bacterial communities like lattices and biofilms. In vitro assays
      evidenced that AutA is a self-associating AT that binds DNA. We suggest that AutA
      mediated autoaggregation might be particularly important for colonization and
      persistence of the pathogen in the nasopharynx of the host. 

PMID- 25059716
TI  - Antibiotics influence the toxicity of the delta endotoxins of Bacillus
      thuringiensis towards the cotton bollworm, Helicoverpa armigera.
AB  - BACKGROUND: The cotton bollworm, Helicoverpa armigera is one of the most
      important crop pests worldwide. It has developed high levels of resistance to
      synthetic insecticides, and hence, Bacillus thuringiensis (Bt) formulations are
      used as a safer pesticide and the Bt genes have been deployed in transgenic crops
      for controlling this pest. There is an apprehension that H. armigera might
      develop resistance to transgenic crops in future. Therefore, we studied the role
      of gut microbes by eliminating them with antibiotics in H. armigera larvae on the
      toxicity of Bt toxins against this pest. RESULTS: Commercial formulation of Bt
      (Biolep(r)) and the pure Cry1Ab and Cry1Ac toxin proteins were evaluated at ED50,
      LC50, and LC90 dosages against the H. armigera larvae with and without
      antibiotics (which removed the gut microbes). Lowest H. armigera larval mortality
      due to Bt formulation and the Bt toxins Cry1Ab and Cry1Ac was recorded in insects
      reared on diets with 250 and 500 MUg ml-1 diet of each of the four antibiotics
      (gentamicin, penicillin, rifampicin, and streptomycin), while the highest larval
      mortality was recorded in insects reared on diets without the antibiotics.
      Mortality of H. armigera larvae fed on diets with Bt formulation and the delta
      endotoxins Cry1Ab and Cry1Ac was inversely proportional to the concentration of
      antibiotics in the artificial diet. Nearly 30% reduction in larval mortality was
      observed in H. armigera larvae from F1 to F3 generation when the larvae were
      reared on diets without antibiotics (with gut microbes) and fed on 0.15% Bt or 12
      MUg Cry1Ab or Cry1Ac ml-1 diet, indicating development of resistance to Bt in the
      presence of gut microflora. However, there were no differences in larval
      mortality due to Bt, Cry1Ab or Cry1Ac across generations in insects when they
      were reared on diets with 250 MUg of each antibiotic ml-1 diet (without gut
      microflora). CONCLUSIONS: The results suggested that antibiotics which eliminated
      gut microflora influenced the toxicity of Bt towards H. armigera, and any
      variation in diversity and abundance of gut microflora will have a major bearing
      on development of resistance to Bt toxins applied as foliar sprays or deployed in
      transgenic crops for pest management.

PMID- 25059717
TI  - Photodynamic diagnostic ureterorenoscopy with orally administered 5
      aminolaevulinic acid as photosensitiser: how I do it.
AB  - OBJECTIVE: To explain our use of photodynamic diagnostic ureterorenoscopy, we
      provide a detailed description of the choice of photosensitiser, equipment
      needed, a safety profile, and pointers on our technique. TECHNIQUE: Patients are
      given oral 5-aminolaevulinic acid (5-ALA) as a photosensitiser 3-4 h pre
      operatively, and by using a Xenon blue light source, an eyepiece which blocks
      light below 450 nm which is fitted onto the ureterorenoscope, we are able to
      conduct a thorough photodiagnosis of the upper urinary tract. CONCLUSION: Our
      technique of photodynamic diagnostic ureterorenoscopy has shown that the
      sensitivity, specificity and detection rates of upper urinary tract lesions can
      be significantly increased with the use of oral 5-ALA. Therefore, we provide a
      detailed explanation of the use of oral 5-ALA photosensitiser, indications and
      contraindications of the technique in addition to equipment used and potential
      complications of the procedures.

PMID- 25059718
TI  - Life Experiences of People Affected by Crohn's Disease and Their Support
      Networks: Scoping Review.
AB  - This scoping review identifies and describes relevant studies related to the
      evidence published on life experiences and perceived social support of people
      affected by Crohn's disease. Twenty-three studies were definitely selected and
      analyzed for the topics explored. The overall findings show patients' needs and
      perceptions. There is a lack of evidence about patients' perceived needs as well
      as the understanding of social support that has contributed to improve their life
      experiences with that chronic illness. Lack of energy, loss of body control, body
      image damaged due to different treatments and surgeries, symptoms related to fear
      of disease, feeling burdened loss related to independence, and so on are some of
      the concerns with having to live with those affected by the Crohn. To underline
      those experiences through this scoping review provides valuable data for health
      care teams, especially for the nursing profession, considered by those affected
      as one of the main roles along the whole pathological process. This review
      provides the basis for developing broader research on the relatively
      underexplored topics and consequently improves specific programs that could
      address patients' needs. 

PMID- 25059719
TI  - Knowledge sources for evidence-based practice in rheumatology nursing.
AB  - As rheumatology nursing develops and extends, knowledge about current use of
      knowledge in rheumatology nursing practice may guide discussions about future
      knowledge needs. To explore what perceptions rheumatology nurses have about their
      knowledge sources and about what knowledge they use in their practice, 12 nurses
      working in specialist rheumatology were interviewed using a semi-structured
      interview guide. The data were analyzed using conventional qualitative content
      analysis. The analysis yielded four types of knowledge sources in clinical
      practice: interaction with others in the workplace, contacts outside the
      workplace, written materials, and previous knowledge and experience. Colleagues,
      and physicians in particular, were important for informal learning in daily
      rheumatology practice. Evidence from the medical arena was accessed through
      medical specialists, while nursing research was used less. Facilitating informal
      learning and continuing formal education is proposed as a way toward a more
      evidence-based practice in extended roles. 

PMID- 25059720
TI  - Structural basis for the extended CAP-Gly domains of p150(glued) binding to
      microtubules and the implication for tubulin dynamics.
AB  - p150(glued) belongs to a group of proteins accumulating at microtubule plus ends
      (+TIPs). It plays a key role in initiating retrograde transport by recruiting and
      tethering endosomes and dynein to microtubules. p150(glued) contains an N
      terminal microtubule-binding cytoskeleton-associated protein glycine-rich (CAP
      Gly) domain that accelerates tubulin polymerization. Although this
      copolymerization is well-studied using light microscopic techniques, structural
      consequences of this interaction are elusive. Here, using electron-microscopic
      and spectroscopic approaches, we provide a detailed structural view of
      p150(glued) CAP-Gly binding to microtubules and tubulin. Cryo-EM 3D
      reconstructions of p150(glued)-CAP-Gly complexed with microtubules revealed the
      recognition of the microtubule surface, including tubulin C-terminal tails by CAP
      Gly. These binding surfaces differ from other retrograde initiation proteins like
      EB1 or dynein, which could facilitate the simultaneous attachment of all
      accessory components. Furthermore, the CAP-Gly domain, with its basic extensions,
      facilitates lateral and longitudinal interactions of tubulin molecules by
      covering the tubulin acidic tails. This shielding effect of CAP-Gly and its basic
      extensions may provide a molecular basis of the roles of p150(glued) in
      microtubule dynamics. 

PMID- 25059721
TI  - Tumor necrosis factor-alpha-induced nuclear factor-kappaB activation in human
      cardiomyocytes is mediated by NADPH oxidase.
AB  - An elevated level of tumor necrosis factor (TNF)-alpha is implicated in several
      cardiovascular diseases including heart failure. Numerous reports have
      demonstrated that TNF-alpha activates nuclear factor (NF)-kappaB, resulting in
      the upregulation of several genes that regulate inflammation, proliferation, and
      apoptosis of cardiomyocytes. Nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase, a major source of reactive oxygen species (ROS), is also activated by
      TNF-alpha and plays a crucial role in redox-sensitive signaling pathways. The
      present study investigated whether NADPH oxidase mediates TNF-alpha-induced NF
      kappaB activation and NF-kappaB-mediated gene expression. Human cardiomyocytes
      were treated with recombinant TNF-alpha with or without pretreatment with
      diphenyleneiodonium (DPI) and apocynin, inhibitors of NADPH oxidase. TNF-alpha
      induced ROS production was measured using 5-(and-6)-chloromethyl-2', 7'
      dichlorodihydrofluorescein diacetate assay. TNF-alpha-induced NF-kappaB
      activation was also examined using immunoblot; NF-kappaB binding to its binding
      motif was determined using a Cignal reporter luciferase assay and an
      electrophoretic mobility shift assay. TNF-alpha-induced upregulation of
      interleukin (IL)-1beta and vascular cell adhesion molecule (VCAM)-1 was
      investigated using real-time PCR and immunoblot. TNF-alpha-induced ROS production
      in cardiomyocytes was mediated by NADPH oxidase. Phosphorylation of IKK
      alpha/beta and p65, degradation of IkappaBalpha, binding of NF-kappaB to its
      binding motif, and upregulation of IL-1beta and VCAM-1 induced by TNF-alpha were
      significantly attenuated by treatment with DPI and apocynin. Collectively, these
      findings demonstrate that NADPH oxidase plays a role in regulation of TNF-alpha
      induced NF-kappaB activation and upregulation of proinflammatory cytokines, IL
      1beta and VCAM-1, in human cardiomyocytes. 

PMID- 25059723
TI  - Detection of milk oligosaccharides in plasma of infants.
AB  - Human milk oligosaccharides (HMO) are one of the major components of human milk.
      HMO are non-digestible by the human gut, where they are known to play important
      functions as prebiotics and decoys for binding pathogens. Moreover, it has been
      proposed that HMO may provide sialic acids to the infant that are important in
      brain development, however this would require absorption of HMO into the
      bloodstream. HMO have consistently been found in the urine of humans and other
      mammals, suggesting systemic absorption. Here, we present a procedure for the
      profiling of milk oligosaccharides (MO) in plasma samples obtained from 13 term
      infants hospitalized for surgery for congenital heart disease. The method
      comprises protein denaturation, oligosaccharide reduction, and porous graphitized
      carbon solid phase extraction for purification followed by analysis using nHPLC
      PGC-chip-TOF-MS. Approximately 15 free MO were typically observed in the plasma
      of human infants, including LNT, LDFP, LNFT, 3'SL, 6'SL, 3'SLN, and 6'SLN, of
      which the presence was confirmed using fragmentation studies. A novel third
      isomer of SLN, not found in human or bovine milk was also consistently detected.
      Differences in the free MO profiles were observed between infants that were
      totally formula-fed and infants that received at least some part breast milk. Our
      results indicate that free MO similar in structure to those found in human milk
      and urine are present in the blood of infants. The method and results presented
      here will facilitate further research toward the possible roles of free MO in the
      development of the infant. 

PMID- 25059724
TI  - Lysis of gram-positive and gram-negative bacteria by antibacterial porous
      polymeric monolith formed in microfluidic biochips for sample preparation.
AB  - Bacterial cell lysis is demonstrated using polymeric microfluidic biochips
      operating via a hybrid mechanical shearing/contact killing mechanism. These
      biochips are fabricated from a cross-linked poly(methyl methacrylate) (X-PMMA)
      substrate by well-controlled, high-throughput laser micromachining. The unreacted
      double bonds at the surface of X-PMMA provide covalent bonding for the formation
      of a porous polymeric monolith (PPM), thus contributing to the mechanical
      stability of the biochip and eliminating the need for surface treatment. The
      lysis efficiency of these biochips was tested for gram-positive (Enterococcus
      saccharolyticus and Bacillus subtilis) and gram-negative bacteria (Escherichia
      coli and Pseudomonas fluorescens) and confirmed by off-chip PCR without further
      purification. The influence of the flow rate when pumping the bacterial
      suspension through the PPM, and of the hydrophobic-hydrophilic balance on the
      cell lysis efficiency was investigated at a cell concentration of 10(5) CFU/mL.
      It was shown that the contribution of contact killing to cell lysis was more
      important than that of mechanical shearing in the PPM. The biochip showed better
      lysis efficiency than the off-chip chemical, mechanical, and thermal lysis
      techniques used in this work. The biochip also acts as a filter that isolates
      cell debris and allows PCR-amplifiable DNA to pass through. The system performs
      more efficient lysis for gram-negative than for gram-positive bacteria. The
      biochip does not require chemical/enzymatic reagents, power consumption, or
      complicated design and fabrication processes, which makes it an attractive on
      chip lysis device that can be used in sample preparation for genetics and point
      of-care diagnostics. The biochips were reused for 20 lysis cycles without any
      evidence of physical damage to the PPM, significant performance degradation, or
      DNA carryover when they were back-flushed between cycles. The biochips
      efficiently lysed both gram-positive and gram-negative bacteria in about 35 min
      per lysis and PPM regeneration cycle. 

PMID- 25059722
TI  - Effects of dietary sea cucumber saponin on the gene expression rhythm involved in
      circadian clock and lipid metabolism in mice during nighttime-feeding.
AB  - In mammals, clock rhythms exist not only in the suprachiasmatic nucleus, which is
      entrained by light/dark (LD) cycles, but also in most peripheral tissues. Recent
      studies have revealed that most physiology and behavior are subject to well
      controlled daily oscillations; similarly, metabolic state influences the diurnal
      rhythm too. Previous studies have indicated that dietary sea cucumber saponin
      (SCS) could improve glucose and lipid metabolism of rodent. However, whether SCS
      could affect the expression of clock genes, which is involved in lipid
      metabolism, is unknown at present. The aim of this study is to investigate the
      effects of SCS on the clock and clock-controlled genes involved in lipid
      metabolism. ICR male mice were divided into a control and SCS group mice (add
      0.03% sea cucumber saponin to regular chow) and were fed at night (2030-0830
      hours). After 2 weeks, clock genes expression in brain and liver, blood glucose,
      hormones, and lipid metabolic markers were analyzed. The results showed that
      dietary SCS caused alteration in rhythms and/or amplitudes of clock genes was
      more significant in brain than in liver. In addition, peroxisome proliferator
      activated receptor (PPARalpha), sterol regulatory element binding protein-1c
      (SREBP-1c), together with their target genes carnitine palmitoyl transferase
      (CPT), and fatty acid synthase (FAS) showed marked changes in rhythm and/or
      amplitude in SCS group mice. These results suggested that SCS could affect the
      daily expression patterns of clock genes in brain and liver tissues, and alter
      the clock-controlled genes involved in lipid metabolism.

PMID- 25059725
TI  - Boron nitride nanotubes as novel sorbent for solid-phase microextraction of
      polycyclic aromatic hydrocarbons in environmental water samples.
AB  - Boron nitride nanotube (BNNT) is a novel material that shows potential ability in
      capturing organic pollutants. In this study, BNNTs fixed on a stainless steel
      fiber by a sol-gel technique were used as sorbent for solid-phase
      microextraction. Five polycyclic aromatic hydrocarbons with different numbers of
      aromatic rings were selected as target analysts. Gas chromatography coupled with
      tandem mass spectrometry was used for detection and quantitative determination.
      Under optimized conditions, the experimental results show a wide range of
      linearity (1 to 1,000 ng L(-1)), less than 10.1 % repeatability of relative
      standard deviation, and low detection limits (0.08 to 0.39 ng L(-1)). In
      addition, the fabricated fiber offered good thermal and chemical stability. The
      proposed method was successfully applied for the analysis of real water samples,
      and satisfactory results were obtained with relative recoveries ranging from 80.2
      to 116.8 %. The results demonstrated that BNNTs could be used as sorbent for the
      analysis of environmental pollutants at trace levels. 

PMID- 25059726
TI  - Government gives the go ahead for mitochondrial donation during IVF.

PMID- 25059727
TI  - The randomized crossover comparison of airway sealing with the laryngeal mask
      airway Supreme(TM) at three different intracuff pressures in children.
AB  - BACKGROUND: An intracuff pressure of 80 cm H2 O in the adult-sized laryngeal mask
      airway Supreme has been recommended to obtain a higher oropharyngeal leak
      pressure (OLP). However, the intracuff pressure for the higher OLP in the
      pediatric laryngeal mask airway Supreme could be different from that in the adult
      sized laryngeal mask airway Supreme. Thus, we measured and compared OLP at three
      intracuff pressures of 40, 60, and 80 cm H2 O in the pediatric laryngeal mask
      airway Supreme. METHODS: This study was designed as a randomized crossover study
      and enrolled 36 children, aged 0-108 months and 5-30 kg in weight. After
      insertion of the laryngeal mask airway Supreme, oropharyngeal leak pressure (OLP)
      was measured at intracuff pressures of 40, 60, and 80 cm H2 O according to one of
      six sequences produced on the basis of 3 * 6 Williams crossover design. During
      the intraoperative period, the laryngeal mask airway Supreme was maintained using
      the last intracuff pressure of the allocated sequence. The intraoperative and
      postoperative complications were compared among three maintenance intracuff
      pressures. RESULTS: OLP at the intracuff pressure of 60 cm H2 O was significantly
      higher than that of 40 cm H2 O (17.9 +/- 3.9 vs 16.9 +/- 4.2 cm H2 O, P = 0.004)
      and was comparable with that of 80 cm H2 O (17.9 +/- 3.9 vs 17.8 +/- 4.6 cm H2 O,
      P = 0.938). There were no significant differences of intraoperative and
      postoperative complications among the three maintenance intracuff pressures.
      CONCLUSION: Our results suggest that the use of an intracuff pressure of 60 cm H2
      O in pediatric laryngeal mask airway Supreme provides a higher OLP compared with
      40 cm H2 O.

PMID- 25059728
TI  - Rupture of zwitterionic lipid vesicles by an amphipathic, alpha-helical peptide:
      indirect effects of sensor surface and implications for experimental analysis.
AB  - Surface-based measurement approaches offer competitive advantages for studying
      lipid membranes and membrane-active drug candidates. Continued development of
      surface-based membrane assays for pharmaceutical and biotechnology applications
      should account for physicochemical properties of the sensor surface. As a model
      system, the rupture of surface-adsorbed, zwitterionic 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC) lipid vesicles by an amphipathic, alpha-helical
      (AH) peptide, which attaches to the vesicle surface and destabilizes the
      membrane, was investigated herein. The kinetics of vesicle rupture on three
      different sensor surfaces (gold, titanium oxide, and aluminum oxide) were tracked
      by simultaneous quartz crystal microbalance-dissipation (QCM-D) and ellipsometry.
      On all three surfaces, complete vesicle rupture was observed. However, the
      corresponding kinetics of the vesicle rupture process and its sub-steps varied
      significantly between the three surfaces. In particular, the experimental data
      supports that the vesicle-substrate interaction influences the rupture process
      via differences in vesicle shape and lipid-substrate adhesion. 

PMID- 25059729
TI  - Single molecule approaches: watching DNA repair one molecule at a time. Preface.

PMID- 25059730
TI  - Two cases of severe hidradenitis suppurativa with failure of anakinra therapy.

PMID- 25059731
TI  - Does child-parent resemblance in body weight status vary by sociodemographic
      factors in the USA?
AB  - BACKGROUND: Clustered obese parents and children are prevalent, but there is
      little knowledge about whether and how child-parent resemblance varies by
      sociodemographic groups. METHODS: This paper used nationally representative data
      from the National Health and Nutrition Examination Survey III (NHANES: 1988
      1994). We matched 4958 parents with 6765 children aged 2-16 years old for whom we
      had complete data on body mass index (BMI), overweight and obesity status.
      Correlation coefficients and kappa statistics between parents' and children's BMI
      and body weight status were calculated for different sociodemographic groups.
      Multivariate linear and logistic regression models were fit to study the child
      parent resemblance and socioeconomic and demographic differences in the
      resemblance. RESULTS: The child-parent correlation coefficients for BMI were
      greater in Caucasians than in minorities and greater in groups with higher
      socioeconomic status. The mother-child resemblance in BMI was negatively
      associated with child age (p<0.001). The mother-daughter resemblance in
      overweight was significantly lower in non-Hispanic blacks (OR=0.53, 95% CI (0.36
      to 0.78)) and Mexican Americans (OR=0.58, 95% CI (0.36 to 0.93)) than in
      Caucasians. The father-child resemblance in overweight was significantly lower in
      high school graduates compared with those with less-than-high-school-graduate
      fathers (OR=0.53, 95% CI (0.37 to 0.77) for father-son dyads and OR=0.69, 95% CI
      (0.50 to 0.96) for father-daughter dyads). Similar results were found for parent
      child resemblance in obesity. CONCLUSIONS: Child-parent resemblance in body
      weight status exists across sociodemographic groups in the USA, but it varies by
      demographics and socioeconomic status.

PMID- 25059732
TI  - Amenable mortality by household income and living arrangements: a linked register
      based study of Finnish men and women in 2000-2007.
AB  - BACKGROUND: Mortality amenable to healthcare interventions has increasingly been
      used as an indirect indicator of the effect of healthcare on health inequalities.
      Studies have consistently shown socioeconomic differences in amenable mortality,
      but evidence on the joint effects of multiple socioeconomic and demographic
      factors is limited. We examined whether income and living arrangements have an
      independent effect on amenable mortality taking into account other dimensions of
      social position. METHODS: The longitudinal and yearly updated individual level
      data were derived from different administrative registers and obtained from
      Statistics Finland. The data set includes an 11% random sample of all individuals
      aged 25-74 years at the end of 1999 and an 80% oversample of deaths in the follow
      up period between 2000 and 2007. We used Cox proportional hazard regression with
      appropriate weights. RESULTS: We found twofold to threefold differences in
      amenable mortality between the top and bottom income quintiles. These differences
      were found to be largely attenuated by economic activity and living arrangements.
      We also found differences in amenable mortality by living arrangements suggesting
      that those living alone, as well as lone parents and those cohabiting have higher
      amenable mortality. These differences were largely independent of our indicators
      of socioeconomic position and economic activity. CONCLUSIONS: While our results
      give indirect support to the hypothesis that income differences in amenable
      mortality may be at least partially due to barriers in access to care, the large
      independent effects of living arrangements on amenable mortality suggest that
      seeking care may also have an impact.

PMID- 25059733
TI  - Serum oestradiol levels in male partners of infertile couples.
AB  - A prospective clinical study was performed in the reproduction centre of Ichikawa
      General Hospital (Chiba, Japan) to investigate the relationship between sperm
      quality and serum oestradiol (E2) level in male partners of infertile couples.
      The semen parameters and blood samples were assessed in relation to several
      variables, including body mass index (BMI) and serum oestradiol (E2) levels. Four
      hundred and nine male partners of infertile couples aged 22-55 years (mean: 36.5
      years) were referred to the reproduction centre. In total, 143 patients (35.0%)
      were included in the low E2 level group (18 pg ml(-1) >= E2). Serum E2 levels
      were slightly correlated with testosterone levels, BMI and serum FSH levels.
      Total motile sperm count and morphology were decreased in low E2 level group. In
      multivariate analysis, serum testosterone, E2 levels, existence of varicocele and
      age were risk factors for decreased semen quality. Serum E2 might be associated
      with BMI, serum testosterone level and spermatogenesis.

PMID- 25059734
TI  - Nanoalloying bulk-immiscible iridium and palladium inhibits hydride formation and
      promotes catalytic performances.
AB  - The hydrogen sorption properties of oxide-supported Ir-Pd nanoalloys have been
      determined for the first time, and correlated with their catalytic behavior. The
      addition of Ir to Pd suppresses hydride formation and leads to improved catalytic
      performances with respect to pure metals in the preferential oxidation of CO in
      H2 excess (PROX). 

PMID- 25059735
TI  - Core content for training in venous and lymphatic medicine.
AB  - The major venous societies in the United States share a common mission to improve
      the standards of medical practitioners, the educational goals for teaching and
      training programs in venous disease, and the quality of patient care related to
      the treatment of venous disorders. With these important goals in mind, a task
      force made up of experts from the specialties of dermatology, interventional
      radiology, phlebology, vascular medicine, and vascular surgery was formed to
      develop a consensus document describing the Core Content for venous and lymphatic
      medicine and to develop a core educational content outline for training. This
      outline describes the areas of knowledge considered essential for practice in the
      field, which encompasses the study, diagnosis, and treatment of patients with
      acute and chronic venous and lymphatic disorders. The American Venous Forum and
      the American College of Phlebology have endorsed the Core Content. 

PMID- 25059736
TI  - Impact of graduated compression stockings on the prevention of post-thrombotic
      syndrome - results of a randomized controlled trial.
AB  - OBJECTIVE: Post-thrombotic syndrome is a chronic complication of acute deep
      venous thrombosis in the lower extremity. The role of graduated compression
      stockings in the prevention of post-thrombotic syndrome has been studied with
      opinion being divided on the beneficial effects. We aim to answer this question
      with a randomized controlled study that uses multiple scoring instruments to
      assess post-thrombotic syndrome. METHODS: Sixty-nine consecutive patients with
      acute deep venous thrombosis diagnosed by duplex ultrasonography were randomized
      to treatment with graduated compression stockings or no graduated compression
      stockings. Venous Clinical Severity Score and Villalta-Prandoni Score, commonly
      used scoring systems, were used to appraise post-thrombotic syndrome at 3, 6, 12,
      18, and 24 months following diagnosis of deep venous thrombosis. In both scoring
      systems, the individual either had post-thrombotic syndrome or no post-thrombotic
      syndrome. Cumulative incidence was computed using Kaplan-Meier analysis. Relative
      risk was assessed for age, obesity, varicose veins, and iliofemoral deep venous
      thrombosis. RESULTS: As measured by both Villalta-Prandoni Score and Venous
      Clinical Severity Score instruments, the graduated compression stockings group
      had a lower incidence of post-thrombotic syndrome compared to the control group,
      but only when one month was used as cut off time for the first diagnosis of post
      thrombotic syndrome. When 6 or 12 months were used, there was no difference in
      the incidence of post-thrombotic syndrome between the two groups. The burden of
      post-thrombotic syndrome was significantly more when the Villalta-Prandoni Score
      instrument (~75%) was used as compared to the Venous Clinical Severity Score
      instrument (~30%) at 24 months' follow-up. Obesity was the only statistically
      significant predictor for the development of post-thrombotic syndrome.
      CONCLUSION: As assessed by both Villalta-Prandoni Score and Venous Clinical
      Severity Score instruments, use of graduated compression stockings does not
      reduce the incidence of post-thrombotic syndrome. There is a significant
      difference in the incidence post-thrombotic syndrome as detected by Villalta
      Prandoni Score and Venous Clinical Severity Score instruments with incidence of
      post-thrombotic syndrome dependent on instrument and cut off time interval used
      to assess post-thrombotic syndrome. However, larger prospective studies are
      required to confirm these differences.

PMID- 25059737
TI  - Vitiligo: what's new in the psycho-neuro-endocrine-immune connection and related
      treatments.
AB  - Vitiligo is an acquired depigmentary skin disorder of unknown origin
      characterized by well-demarcated, white macules of varying size and distribution.
      Despite relevant new research and progresses, why melanocytes disappear to induce
      the characteristic achromic lesions of vitiligo is not fully understood. In spite
      of recent findings implicating genetic, immune and oxidative stress factors, the
      exact pathogenesis of vitiligo remains obscure. An innovative concept based on a
      functional cross-talk between the nervous and immune system is emerging.
      Neuropeptides released from peripheral nerve endings could synergize with new
      cytokines to adversely affect melanocyte function and viability. Evidence is
      increasing regarding the role of neuropeptides in the pathogenesis of vitiligo
      and a new winning approach to vitiligo therapy based on neuropeptides regulation
      is at the horizon. 

PMID- 25059738
TI  - Mathematica numerical simulation of peristaltic biophysical transport of a
      fractional viscoelastic fluid through an inclined cylindrical tube.
AB  - This paper studies the peristaltic transport of a viscoelastic fluid (with the
      fractional second-grade model) through an inclined cylindrical tube. The wall of
      the tube is modelled as a sinusoidal wave. The flow analysis is presented under
      the assumptions of long wave length and low Reynolds number. Caputo's definition
      of fractional derivative is used to formulate the fractional differentiation.
      Analytical solutions are developed for the normalized momentum equations.
      Expressions are also derived for the pressure, frictional force, and the
      relationship between the flow rate and pressure gradient. Mathematica numerical
      computations are then performed. The results are plotted and analysed for
      different values of fractional parameter, material constant, inclination angle,
      Reynolds number, Froude number and peristaltic wave amplitude. It is found that
      fractional parameter and Froude number resist the flow pattern while material
      constant, Reynolds number, inclination of angle and amplitude aid the peristaltic
      flow. Furthermore, frictional force and pressure demonstrate the opposite
      behaviour under the influence of the relevant parameters emerging in the
      equations of motion. The study has applications in uretral biophysics, and also
      potential use in peristaltic pumping of petroleum viscoelastic bio-surfactants in
      chemical engineering and astronautical applications involving conveyance of non
      Newtonian fluids (e.g. lubricants) against gravity and in conduits with
      deformable walls. 

PMID- 25059740
TI  - Personalized medicine and human genetic diversity.
AB  - Human genetic diversity has long been studied both to understand how genetic
      variation influences risk of disease and infer aspects of human evolutionary
      history. In this article, we review historical and contemporary views of human
      genetic diversity, the rare and common mutations implicated in human disease
      susceptibility, and the relevance of genetic diversity to personalized medicine.
      First, we describe the development of thought about diversity through the 20th
      century and through more modern studies including genome-wide association studies
      (GWAS) and next-generation sequencing. We introduce several examples, such as
      sickle cell anemia and Tay-Sachs disease that are caused by rare mutations and
      are more frequent in certain geographical populations, and common treatment
      responses that are caused by common variants, such as hepatitis C infection. We
      conclude with comments about the continued relevance of human genetic diversity
      in medical genetics and personalized medicine more generally. 

PMID- 25059739
TI  - Nonclassical T cells and their antigens in tuberculosis.
AB  - T cells that recognize nonpeptidic antigens, and thereby are identified as
      nonclassical, represent important yet poorly characterized effectors of the
      immune response. They are present in large numbers in circulating blood and
      tissues and are as abundant as T cells recognizing peptide antigens. Nonclassical
      T cells exert multiple functions including immunoregulation, tumor control, and
      protection against infections. They recognize complexes of nonpeptidic antigens
      such as lipid and glycolipid molecules, vitamin B2 precursors, and phosphorylated
      metabolites of the mevalonate pathway. Each of these antigens is presented by
      antigen-presenting molecules other than major histocompatibility complex (MHC),
      including CD1, MHC class I-related molecule 1 (MR1), and butyrophilin 3A1
      (BTN3A1) molecules. Here, we discuss how nonclassical T cells participate in the
      recognition of mycobacterial antigens and in the mycobacterial-specific immune
      response. 

PMID- 25059741
TI  - Alveolar T-helper type-2 immunity in atopic asthma is associated with poor
      clinical control.
AB  - Real-world evaluation studies have shown that many patients with asthma remain
      symptomatic despite treatment with inhaled corticosteroids (ICSs). As
      conventional ICSs have poor access to the peripheral airways, the aim of the
      present paper was to study the relationship between peripheral airway
      inflammation and clinical control in allergic asthma. Consequently, bronchial and
      transbronchial biopsies were obtained from patients with poorly controlled asthma
      [n=12, asthma control test (ACT) score<20], patients with well-controlled asthma
      (n=12, ACT score>=20) and healthy controls (n=8). Tissue sections were
      immunostained to assess multiple leucocyte populations. To determine the degree
      of T-helper type-2 (Th2) immunity, the logarithmic value of the ratio between Th2
      cells/mm2 and Th1 cells/mm2 was used as a surrogate score for Th2-skewed
      immunity. In the bronchi, the leucocyte infiltration pattern and the Th2-score
      were similar between patients with well-controlled asthma and those with poorly
      controlled asthma. In contrast, in the alveolar parenchyma, the expression of T
      helper cells was significantly higher in patients with poorly controlled asthma
      than in patients with well-controlled asthma (P<0.01). Furthermore, the alveolar
      Th2-score was significantly higher in patients with poorly controlled asthma
      (median 0.4) than in the controlled patients (median -0.10, P<0.05). In addition,
      in contrast with bronchial Th2-score, the alveolar Th2-score correlated
      significantly with ACT score (rs=-0.62, P<0.01) in the pooled asthma group.
      Collectively, our data reveal an alveolar Th2-skewed inflammation, specifically
      in asthmatic patients who are poorly controlled with ICSs, and suggest that
      pharmacological targeting of the peripheral airways may be beneficial in this
      large patient category.

PMID- 25059742
TI  - Drug-eluting stents versus bare metal stents prior to noncardiac surgery.
AB  - BACKGROUND: The safety of drug-eluting stents (DES) vs. bare metal stents (BMS)
      in the perioperative setting, a heightened state of inflammation and thrombosis
      is not well defined. METHODS: All adults undergoing noncardiac surgical (NCS)
      procedures within 1 year following percutaneous coronary intervention (PCI) in
      Massachusetts between April 1, 2004, and September 30, 2007, were identified from
      an administrative claims database. Patients were divided into those who received
      BMS vs. DES at index PCI. Primary net clinical outcome was death, myocardial
      infarction (MI) or bleeding within 30 days of NCS. Primary clinical outcome was
      30-day death or MI. RESULTS: Among 8,415 (22% BMS) patients that satisfied our
      inclusion criteria, 1,838 BMS patients were matched with 3,565 DES patients with
      similar propensity scores. In the DES cohort, the 30-day primary net clinical
      outcome rate was lower with longer time from PCI to NCS (P = 0.02) with lowest
      rates if NCS was performed after 90 days from PCI (event rate 8.57, 7.53, 5.21,
      and 5.75% for 1-30, 31-90, 91-180, and 181-365 days from PCI to NCS). However, in
      the BMS cohort, the event rate was uniformly high regardless of the time from PCI
      to NCS (P = 0.60) (event rate 8.20, 6.56, 8.05, and 8.82% for 1-30, 31-90, 91
      180, and 181-365 days from PCI to NCS). There was no significant difference
      between DES and the BMS group for 30-day primary net clinical outcome (6.64 vs.
      7.89%; P = 0.10), but there was a 26% lower odds of primary clinical outcome (OR
      = 0.74, 95% CI 0.58-0.94) with DES when compared with BMS, driven mainly by
      differences in event rates when NCS was performed >90 days post PCI. CONCLUSION:
      DES implantation was not associated with higher adverse events after NCS.
      Moreover, the incidence of adverse events following NCS was lower when NCS was
      performed >90 days post-DES implantation suggesting that it may not be necessary
      to wait until 12 months post PCI with DES before NCS.

PMID- 25059743
TI  - A review of abortion laws in Western-European countries. A cross-national
      comparison of legal developments between 1960 and 2010.
AB  - The extent to which women have had access to legal abortions has changed
      dramatically in Western-Europe between 1960 and 2010. In most countries, abortion
      laws developed from completely banning abortion to allowing its availability on
      request. Both the timing and the substance of the various legal developments
      differed dramatically between countries. Existing comparative studies on abortion
      laws in Western-European countries lack detail, usually focus either on first
      trimester abortions or second trimester abortions, cover a limited time-span and
      are sometimes inconsistent with one another. Combining information from various
      primary and secondary sources, we show how and when the conditions for legally
      obtaining abortion during the entire gestation period in 20 major Western
      European countries have changed between 1960 and 2010. We also construct a cross
      nationally comparable classification of procedural barriers that limit abortion
      access. Our cross-national comparison shows that Western-Europe witnessed a
      general trend towards decreased restrictiveness of abortion laws. However, legal
      approaches to regulating abortion are highly different in detail. Abortion access
      remains limited, sometimes even in countries where abortion is legally available
      without restrictions relating to reasons. 

PMID- 25059744
TI  - Evaluation of a possible predictor for Federal Joint Committee decisions on early
      benefit assessments according to the German act on the reform of the market for
      medicinal products.
AB  - OBJECTIVES: As of 1st January 2011 the German drug market is regulated by the act
      on the reform of the market for medicinal products (AMNOG). Since then the normal
      procedure for reimbursement of a new pharmaceutical is a benefit assessment by
      the joint federal committee (G-BA) which determines one of six additional benefit
      levels. METHODS: In order to evaluate a possible predictor of G-BA decisions, the
      'evaluation of pharmaceutical innovations (EVITA)' score was calculated for 40
      out of 63 dossiers and compared with published G-BA appraisals. RESULTS:
      Univariate ordinary least squares (p<0.001) and ordered logit regression
      (p=0.008) analyses show statistically significant correlations between EVITA
      scores and the G-BA additional benefit levels. Moreover, for the prediction of an
      additional benefit level of at least 'minor', an EVITA score cutpoint of >=3 is
      associated with a sensitivity of 100% and a specificity of 80%. For the
      prediction of an additional benefit level of at least 'considerable', an EVITA
      score cutpoint of >=7.5 is associated with a sensitivity of 100% and a
      specificity of 93.1%. CONCLUSION: The present investigation indicates that the
      EVITA score may have some potential to act as a possible predictor of G-BA
      decisions related to AMNOG early benefit assessments.

PMID- 25059745
TI  - A proposal to improve clarity and communication in the EU Classification process
      for chemicals for carcinogenicity and reproductive and developmental toxicity.
AB  - There is an issue in the EU classification of substances for carcinogenicity and
      for reproductive or developmental toxicity which has brought difficulties to
      those involved in the process. The issue lies in the inability of the
      classification system to distinguish between carcinogens and reproductive
      toxicants with different levels of concern. This has its origins in the early
      years of toxicology when it was thought that a relatively small number of
      chemicals would be either carcinogens or reproductive toxicants, but this has
      turned out not to be the case. This can cause problems in communicating to the
      users of chemicals, including the public, the nature of the hazard presented by
      chemicals. Processes have been developed within the classification system for
      setting specific concentration limits which assess the degree of hazard for
      carcinogens and reproductive toxicants as high, medium or low. However these
      categories are not otherwise used in classification. It is proposed that their
      wider use would bring the advantages of transparency, clarity of communication,
      certainty of the process and would allow chemicals with a high degree of hazard
      to be identified and managed in an appropriate way.

PMID- 25059746
TI  - Risk Factors Associated with Prolonged Mechanical Ventilation after Corrective
      Surgery for Tetralogy of Fallot.
AB  - INTRODUCTION: This study examined early postoperative results to identify
      perioperative factors that are associated with prolonged mechanical ventilation
      (PMV) in tetralogy of Fallot (TOF) patients undergoing corrective surgery.
      METHODS: We retrospectively examined the role of perioperative variables in
      determining the period of mechanical ventilatory support in TOF patients
      undergoing corrective surgery. A total of 821 patients were included in the
      study. The cohort was divided into a PMV group that included patients with >90th
      percentile for duration of mechanical ventilation and a non-PMV group which
      included all other patients. RESULTS: Non-PMV group consisted of 751 patients
      (454 males, 297 females; median age 12 months, interquartile range 8-19 months;
      mean weight 9.60 +/- 2.98 kg). PMV group consisted of 70 patients (51 males, 19
      females; median age 8 months, interquartile range 6.75-13 months; mean weight
      8.64 +/- 1.95 kg). No patients died in the non-PMV group compared with two deaths
      due to acute respiratory distress syndrome in the PMV group. Univariate risk
      factors for PMV included age, weight, left ventricular end-diastolic volume index
      (LVEDVI), McGoon ratio, Nakata index, previous palliative operations,
      cardiopulmonary bypass (CPB) time, aortic cross-clamp (ACC) time, preoperative
      major aortopulmonary collateral arteries (MAPCAs) occlusion by coils in hybrid
      procedure, postoperative right ventricular/left ventricular systolic pressure
      ratio, central venous pressure (CVP), left atrial pressure (LAP), endotracheal
      reintubation, vasoactive-inotropic score (VIS), renal replacement therapy, and
      early-onset ventilator-associated pneumonia (VAP). In a multivariable model, age,
      LVEDVI, McGoon ratio, Nakata index, previous palliative operations, CPB time,
      blood returning to left atrium during surgery as a surrogate marker for
      significant aortopulmonary collateral presence, and early-onset VAP were the
      independent risk factors for PMV. CONCLUSIONS: The risk factors for PMV were age,
      LVEDVI, McGoon ratio, Nakata index, previous palliative operations, CPB time,
      VIS, LAP, blood returning to left atrium during surgery, and early-onset VAP.

PMID- 25059748
TI  - Rapid identification of metal-binding peptoid oligomers by on-resin X-ray
      fluorescence screening.
AB  - N-Substituted glycine peptoid oligomers have recently attracted attention for
      their metal binding capabilities. Due to their efficient synthesis on solid
      phase, peptoids are well suited for generation of compound libraries, followed by
      screening for molecular recognition and other diverse functional attributes.
      Ideally, peptoids could be simultaneously screened for binding to a number of
      metal species. Here, we demonstrate the use of bench-top X-ray fluorescence (XRF)
      instrumentation to screen rapidly, on solid support, a library of peptoid
      oligomers incorporating metal-binding functionalities. A subset of the peptoid
      sequences exhibited significant metal binding capabilities, including a peptoid
      pentamer and a nonamer that were shown to selectively bind nickel. The binding
      capabilities were validated by colorimetric assay and by depletion of Ni(2+) ion
      concentration from solution, establishing bench-top XRF as a rapid, practicable
      high-throughput screening technique for peptoid oligomers. This protocol will
      facilitate discovery of metallopeptoids with unique material properties.

PMID- 25059749
TI  - Gas chromatography mass spectrometry based metabolic profiling reveals biomarkers
      involved in rice-gall midge interactions.
AB  - The Asian rice gall midge (Orseolia oryzae Wood-Mason) is a serious pest of rice
      that causes huge loss in yield. While feeding inside the susceptible host,
      maggots secrete substances that facilitate the formation of a hollow tube-like
      structure called gall and prevent panicle formation. The present investigation
      was carried out to get an account of biochemical changes occurring in the rice
      plant upon gall midge feeding. Metabolic profiling of host tissues from three
      rice varieties, namely, TN1, Kavya, and RP2068, exposed to gall midge biotype 1
      (GMB1), was carried out using gas chromatography mass spectrometry (GC-MS). TN1
      and GMB1 represented compatible interaction, while Kavya and GMB1 as well as
      RP2068 and GMB1 represented incompatible interactions. The current study
      identified several metabolites that could be grouped as resistance,
      susceptibility, infestation, and host features based on their relative abundance.
      These may be regarded as biomarkers for insect-plant interaction in general and
      rice-gall midge interaction in particular. 

PMID- 25059750
TI  - Changing implicit attitudes toward smoking: results from a web-based approach
      avoidance practice intervention.
AB  - Implicit attitudes have been shown to predict smoking behaviors. Therefore, an
      important goal is the development of interventions to change these attitudes.
      This study assessed the effects of a web-based intervention on implicit attitudes
      toward smoking and receptivity to smoking-related information. Smokers (N = 284)
      were recruited to a two-session web-based study. In the first session, baseline
      data were collected. Session two contained the intervention, which consisted of
      assignment to the experimental or control version of an approach-avoidance task
      and assignment to an anti-smoking or control public service announcement (PSA),
      and post-intervention measures. Among smokers with less education and with plans
      to quit, implicit attitudes were more negative for those who completed the
      approach-avoidance task. Smokers with more education who viewed the anti-smoking
      PSA and completed the approach-avoidance task spent more time reading smoking
      related information. An approach-avoidance task is a potentially feasible
      strategy for changing implicit attitudes toward smoking and increasing
      receptivity to smoking-related information.

PMID- 25059747
TI  - Operative versus non-operative treatment for closed, displaced, intra-articular
      fractures of the calcaneus: randomised controlled trial.
AB  - OBJECTIVE: To investigate whether surgery by open reduction and internal fixation
      provides benefit compared with non-operative treatment for displaced, intra
      articular calcaneal fractures. DESIGN: Pragmatic, multicentre, two arm, parallel
      group, assessor blinded randomised controlled trial (UK Heel Fracture Trial).
      SETTING: 22 tertiary referral hospitals, United Kingdom. PARTICIPANTS: 151
      patients with acute displaced intra-articular calcaneal fractures randomly
      allocated to operative (n=73) or non-operative (n=78) treatment. MAIN OUTCOME
      MEASURES: The primary outcome measure was patient reported Kerr-Atkins score for
      pain and function (scale 0-100, 100 being the best possible score) at two years
      after injury. Secondary outcomes were complications; hindfoot pain and function
      (American Orthopaedic Foot and Ankle Society score); general health (SF-36);
      quality of life (EQ-5D); clinical examination; walking speed; and gait symmetry.
      Analysis was by intention to treat. RESULTS: 95% follow-up was achieved for the
      primary outcome (69 in operative group and 74 in non-operative group), and a
      complete set of secondary outcomes were available for 75% of participants. There
      was no significant difference in the primary outcome (mean Kerr-Atkins score 69.8
      in operative group v 65.7 in non-operative group; adjusted 95% confidence
      interval of difference -7.1 to 7.0) or in any of the secondary outcomes between
      treatment groups. Complications and reoperations were more common in those who
      received operative care (estimated odds ratio 7.5, 95% confidence interval 2.0 to
      41.8). CONCLUSIONS: Operative treatment compared with non-operative care showed
      no symptomatic or functional advantage after two years in patients with typical
      displaced intra-articular fractures of the calcaneus, and the risk of
      complications was higher after surgery. Based on these findings, operative
      treatment by open reduction and internal fixation is not recommended for these
      fractures.Trial registration Current Controlled Trials ISRCTN37188541.

PMID- 25059751
TI  - The utility of ancillary tests in monitoring cutaneous melanoma patients to
      detect visceral metastasis.

PMID- 25059752
TI  - Immunohistochemical expression of heat shock proteins, p63 and androgen receptor
      in benign prostatic hyperplasia and prostatic carcinoma in the dog.
AB  - This study compared heat shock proteins Hsp60, Hsp72 and Hsp73, along with p63
      and androgen receptor (AR) immunoexpression between 16 cases of benign prostatic
      hyperplasia (BPH) and 11 prostatic carcinomas (PCa) in dogs. The proportion of
      Hsp60-positive cells was higher in PCa compared with BPH (P = 0.033), whereas the
      frequency and intensity of Hsp73 immunostaining did not differ significantly
      between the two groups. Hsp72-immunostained nuclei formed a discontinuous layer
      along the basement membrane in BPH, whereas cells in this layer in PCa were
      negative or weakly positive. Hsp72 nuclear score showed significant positive
      associations with both p63 (P = 0.016) and AR (P = 0.009) scores. Double
      immunofluorescence revealed Hsp72-p63 and Hsp72-AR co-expressions in basal cell
      nuclei. Aberrant cytoplasmic p63 immunolabelling was observed in 3 of 11 PCa
      cases. These results suggest a role of the combined expression of Hsp72, p63 and
      AR in basal epithelial cells in canine BPH and PCa.

PMID- 25059753
TI  - Expression and clinical significance of RCDG1 in renal cell carcinoma: a novel
      renal cancer-associated gene.
AB  - Recently identified molecular tumor markers have numerous potential applications
      in the diagnosis, therapy and prognostic prediction of renal cell carcinoma
      (RCC). Through bioinformatics-based screening approaches together with validation
      of western blot and immunohistochemical data, the present study identified a
      novel renal cancer-associated gene, preliminarily named Renal Cancer
      Differentiation Gene 1 (RCDG1), originally known as chromosome 4 open reading
      frame 46 (C4orf46). RCDG1 expression was evaluated by western blot analysis of
      RCC and adjacent normal tissues, renal cancer cell lines and normal kidney
      HEK293T cells. Additionally, RCDG1 expression was assessed in 124 RCC paraffin
      sections, including 92 paired adjacent normal tissues, by immunohistochemistry.
      The results showed that RCDG1 was significantly downregulated in RCC tissues as
      compared with normal adjacent tissues (P<0.001), and the expression of RCDG1 in
      clear cell (cc) RCC tissues was significantly lower as compared with that of non
      ccRCC tissues (P=0.005). Furthermore, statistical analysis revealed RCDG1
      expression was negatively correlated with the Fuhrman grade in ccRCC (P=0.008). A
      reduction in RCDG1 expression may be associated with the oncogenesis of RCC and
      the differentiation of ccRCC. Further studies may provide more information about
      the function of RCDG1 gene in RCC.

PMID- 25059754
TI  - Psychometric properties and confirmatory factor analysis of the CASP-19, a
      measure of quality of life in early old age: the HAPIEE study.
AB  - OBJECTIVES: The aim was to assess the reliability and validity of the quality of
      life (QoL) instrument CASP-19, and three shorter versions of CASP-12 in large
      population sample of older adults from the HAPIEE (Health, Alcohol, and
      Psychosocial factors In Eastern Europe) study. METHODS: From the Czech Republic,
      Russia, and Poland, 13,210 HAPIEE participants aged 50 or older completed the
      retirement questionnaire including CASP-19 at baseline. Three shorter 12-item
      versions were also derived from original 19-item instrument. Psychometric
      validation used confirmatory factor analysis, Cronbach's alpha, Pearson's
      correlation, and construct validity. RESULTS: The second-order four-factor model
      of CASP-19 did not provide a good fit to the data. Two-factor CASP-12v.3
      including residual covariances for negative items to account for the method
      effect of negative items had the best fit to the data in all countries (CFI =
      0.98, TLI = 0.97, RMSEA = 0.05, and WRMR = 1.65 in the Czech Republic; 0.96,
      0.94, 0.07, and 2.70 in Poland; and 0.93, 0.90, 0.08, and 3.04 in Russia).
      Goodness-of-fit indices for the two-factor structure were substantially better
      than second-order models. CONCLUSIONS: This large population-based study is the
      first validation study of CASP scale in Central and Eastern Europe (CEE), which
      includes a general population sample in Russia, Poland, and the Czech Republic.
      The results of this study have demonstrated that the CASP-12v.3 is a valid and
      reliable tool for assessing QoL among adults aged 50 years or older. This version
      of CASP is recommended for use in future studies investigating QoL in the CEE
      populations.

PMID- 25059755
TI  - Malignant mixed Mullerian tumor with an extensive squamous-cell carcinomatous
      component: a potential pitfall in liquid-based cervical cytology.
AB  - BACKGROUND: Malignant mixed Mullerian tumors (MMMTs) are aggressive tumors
      arising in the female lower genital tract and characterized by the presence of
      both a malignant epithelial and a mesenchymal component. Here, we report a case
      of an MMMT of the uterine corpus with an extensive squamous-cell carcinomatous
      component processed by liquid-based cytology (LBC). CASE REPORT: An 84-year-old
      woman with a prior history of anal squamous-cell carcinoma, who complained of
      vaginal bleeding, was discovered to have a mass protruding from the uterine
      cervix. A Papanicolaou (Pap) test was performed and the LBC (ThinPrep)
      preparation showed a background of neutrophils and cellular debris. Atypical
      cells were identified that presented with hyperchromatic nuclei, nuclear membrane
      irregularities, multinucleation and abundant cytoplasm with focal keratinization.
      Scattered nucleolated malignant elements were also identified. The cytological
      diagnosis resulted in 'suspicious for squamous-cell carcinoma', favoring primary
      cervical carcinoma rather than extracervical (anal) carcinoma. The histological
      examination showed that it was an MMMT with an extensive squamous-cell
      carcinomatous component. CONCLUSION: This case illustrates the potential
      diagnostic pitfall of MMMTs with extensive squamous-cell carcinomatous components
      in LBC Pap smears. Cytopathologists should keep in mind this diagnostic
      possibility in postmenopausal women who experience vaginal bleeding or spotting.

PMID- 25059757
TI  - Fabrication of wide-bandgap transparent electrodes by using conductive filaments:
      performance breakthrough in vertical-type GaN LED.
AB  - For realizing next-generation solid-state lighting devices, performance
      breakthroughs must be accomplished for nitride-based light-emitting diodes
      (LEDs). Highly transparent conductive electrodes (TCEs) may be key to achieving
      this goal, as they provide uniform current injection and distribution across a
      large device area, eventually increasing the light output power. However, the
      trade-off between electrical conductivity and optical transmittance of LEDs must
      be addressed. Herein, we introduce a novel strategy based on TCEs fabricated
      using wide-bandgap (WB) materials such as SiNx, incorporated beneath the n-type
      electrode of vertical-type LEDs, and show the feasibility of this strategy. We
      employ a novel electrical breakdown (EBD) technique to form conductive filaments
      (or current paths) between a TCE and n-GaN (GaN: gallium nitride). By employing
      the EBD process, we obtain both ohmic behavior for SiNx TCE/n-GaN and a current
      spreading effect across n-GaN. These results demonstrate the tremendous potential
      of WB-TCEs for use in high-performance optoelectronic devices. 

PMID- 25059756
TI  - Prevalence and risk factors for allergic rhinitis in two resource-limited
      settings in Peru with disparate degrees of urbanization.
AB  - BACKGROUND: Allergic rhinitis is a disease with a high global disease burden, but
      risk factors that contribute to this condition are not well understood.
      OBJECTIVE: To assess the prevalence and risk factors of allergic rhinitis in two
      Peruvian populations with disparate degrees of urbanization. METHODS: We
      conducted a population-based, cross-sectional study on 1441 children aged 13-15
      years at enrollment (mean age 14.9 years, 51% boys) to investigate the prevalence
      of allergic disease. We used a standardized, Spanish validated questionnaire to
      determine the prevalence of allergic rhinitis and asked about sociodemographics
      and family history of allergies. Children also underwent spirometry, exhaled
      nitric oxide, allergy skin testing to 10 common household allergens and provided
      a blood sample for measurement of 25OH vitamin D and total serum IgE. RESULTS:
      Overall prevalence of allergic rhinitis was 18% (95% CI 16% to 20%). When
      stratified by site, the prevalence of allergic rhinitis was 23% Lima vs. 13% in
      Tumbes (P < 0.001); however, this difference was no longer significant after
      controlling for subject-specific factors (P = 0.95). There was a strong
      association with other allergic diseases: 53% of children with asthma had
      allergic rhinitis vs. 15% in those without asthma (P < 0.001) and 42% of children
      with eczema vs. 17% of those without eczema (P < 0.001). Important risk factors
      for allergic rhinitis were parental rhinitis (adjusted OR = 3.0, 95% CI 1.9-4.7
      for 1 parent and adjusted OR = 4.4, 95% CI 1.5-13.7 for 2 parents); allergic
      sensitization to common household aeroallergens (1.6, 1.1-2.3); being overweight
      (1.5, 1.0-2.3); exhaled nitric oxide >= 20 ppb (1.9, 1.3-2.7); and total serum
      IgE >= 95th percentile (2.4, 1.2-4.8). Population attributable risk of important
      factors for allergic rhinitis were 25% for high exhaled nitric oxide, 22% for
      allergic sensitization to common household aeroallergens, 22% for paternal
      rhinitis, 10% for being overweight and 7% for an elevated total serum IgE.
      CONCLUSION AND CLINICAL RELEVANCE: Allergic rhinitis was prevalent in both
      settings, and important risk factors include elevated exhaled nitric oxide,
      allergic sensitization to common household aeroallergens, parental rhinitis,
      being overweight and high total serum IgE. When considering subject-specific
      factors, the difference in prevalence between the urban and rural settings became
      non-important.

PMID- 25059758
TI  - Pharmacological characterization of a highly selective and potent partial agonist
      of the MT2 melatonin receptor.
AB  - BACKGROUND/AIMS: The MT2 melatonin receptor is a potential target for treating
      circadian rhythm sleep disorders. This study aims to characterize the recently
      identified MT2 melatonin receptor agonist. METHODS: The pharmacological
      properties of the MT2 melatonin receptor-selective agonist as exemplified by
      compound 1 [N-(2-[7-benzyl-1,6-dihydro-2H-indeno(5,4-b)furan-8
      yl]ethyl)acetamide] were evaluated by use of cell-free binding and cell-based
      functional assays. RESULTS: Competition binding assays using 2
      [(125)I]iodomelatonin revealed rapid, reversible, and high-affinity binding of
      compound 1 to human, mouse, and rat MT2 melatonin receptors. cAMP, ERK1/2, and
      PathHunter beta-arrestin recruitment assays revealed partial agonist activities.
      However, compound 1 induced a more intense internalization of human MT2 melatonin
      receptor than melatonin. Based on studies using structurally related analogs of
      compound 1, we further demonstrated that the extent of internalization is
      independent of the intrinsic efficacy of agonists. CONCLUSION: These findings
      provide novel insights into the relationship between intrinsic agonist efficacy
      and agonist-induced internalization and demonstrate that compound 1 could serve
      as a pharmacological tool for future studies to elucidate the detailed molecular
      mechanism of MT2 receptor internalization.

PMID- 25059759
TI  - Circulatory responses to lower body negative pressure in young Afghans and Danes:
      implications for understanding ethnic effects on blood pressure regulation.
AB  - PURPOSE: We have previously shown that Afghans residing in Denmark for at least
      12 years exhibit a lower 24-h ambulatory blood pressure compared to Danes. The
      purpose of this study was to test the hypothesis that the lower blood pressure
      reflects attenuated compensatory baroreflex responses in the Afghans. METHODS: On
      a controlled diet (2,822 cal/day, 55-75 mmol + 2 mmol Na+/kg/day), 12 young males
      of Afghan (Afghans) and 12 young males of Danish (Danes) origin were exposed to a
      two-step lower body negative pressure (LBNP) protocol of -20 and -50 mmHg,
      respectively, each of 10-min duration. RESULTS: Afghans had lower 24-h systolic
      blood pressure compared to Danes (115 +/- 2 vs. 123 +/- 1 mmHg, p < 0.05).
      Cardiac output and stroke volume were significantly lower in Afghans compared to
      Danes prior to and during each level of LBNP. However, it decreased to the same
      extent in both groups during LBNP. During LBNP of -20 mmHg, plasma noradrenaline
      concentration and plasma renin activity (PRA) increased significantly only in the
      Afghans. At LBNP of -50 mmHg plasma noradrenaline concentration and PRA both
      increased significantly and similarly in the two groups. CONCLUSION: The lower 24
      h ambulatory blood pressure in the Afghans is probably caused by a lower stroke
      volume, which augmented the circulatory and vasoactive hormonal responses to LBNP
      in the Afghans. The lower stroke volume in Afghans residing in Denmark compared
      to that of matched native Danes remains to be explained.

PMID- 25059760
TI  - Acute metabolic, hormonal and psychological responses to cycling with
      superimposed electromyostimulation.
AB  - PURPOSE: The purpose of the present study was to evaluate the effects of
      superimposed electromyostimulation (E) during cycling on the acute hormonal and
      metabolic response, as E might be a useful tool to intensify endurance training
      without performing high external workloads. METHODS: Thirteen subjects
      participated in three experimental trials each lasting 60 min in a randomized
      order. (1) Cycling (C), (2) cycling with superimposed E (C + E) and (3) E. Human
      growth hormone (hGH), testosterone and cortisol were determined before (pre) and
      0', 30', 60', 240' and 24 h after each intervention. Metabolic stimuli and
      perturbations were characterized by lactate and blood gas analysis (pH, base
      excess, bicarbonate, partial pressure of oxygen, partial pressure of carbon
      dioxide). Furthermore, changes of the person's perceived physical state were
      determined. RESULTS: C + E caused the highest increases in cortisol and hGH,
      followed by C and E. Testosterone levels showed no significant differences
      between C + E and C. Metabolic stress was highest during C + E, followed by C and
      E. C + E was also the most demanding intervention from an athlete's point of
      view. CONCLUSION: As cortisol and hGH are known to react in an intensity
      dependent manner, the present study showed that superimposed E is a useful method
      to intensify endurance training, even when performing low to moderate external
      workloads. Even at lower exercise intensities, additional E may allow one to
      induce a high (local) stimulus. It can be speculated, that these acute hormonal
      increases and metabolic perturbations, might play a positive role in optimizing
      long-term training adaptations, similar to those of intense training protocols.

PMID- 25059762
TI  - Fluorine-doped porous single-crystal rutile TiO2 nanorods for enhancing
      photoelectrochemical water splitting.
AB  - Fluorine-doped hierarchical porous single-crystal rutile TiO(2) nanorods have
      been synthesized through a silica template method, in which F(-) ions acts as
      both n-type dopants and capping agents to make the isotropic growth of the
      nanorods. The combination of high crystallinity, abundant surface reactive sites,
      large porosity, and improved electronic conductivity leads to an excellent
      photoelectrochemical activity. The photoanode made of F-doped porous single
      crystals displays a remarkably enhanced solar-to-hydrogen conversion efficiency
      (~0.35 % at -0.33 V vs. Ag/AgCl) under 100 mW cm(-2) of AM=1.5 solar simulator
      illumination that is ten times of the pristine solid TiO(2) single crystals.

PMID- 25059764
TI  - Functional elucidation of antibacterial phage ORFans targeting Pseudomonas
      aeruginosa.
AB  - Immediately after infection, virulent bacteriophages hijack the molecular
      machinery of their bacterial host to create an optimal climate for phage
      propagation. For the vast majority of known phages, it is completely unknown
      which bacterial functions are inhibited or coopted. Early expressed phage genome
      regions are rarely identified, and often filled with small genes with no homology
      in databases (so-called ORFans). In this work, we first analysed the temporal
      transcription pattern of the N4-like Pseudomonas-infecting phages and selected 26
      unknown, early phage ORFans. By expressing their encoded proteins individually in
      the host bacterium Pseudomonas aeruginosa, we identified and further
      characterized six antibacterial early phage proteins using time-lapse microscopy,
      radioactive labelling and pull-down experiments. Yeast two-hybrid analysis
      gaveclues to their possible role in phage infection. Specifically, we show that
      the inhibitory proteins may interact with transcriptional regulator PA0120, the
      replicative DNA helicase DnaB, the riboflavin metabolism key enzyme RibB, the
      ATPase PA0657and the spermidine acetyltransferase PA4114. The dependency of phage
      infection on spermidine was shown in a final experiment. In the future, knowledge
      of how phages shut down their hosts as well ass novel phage-host interaction
      partners could be very valuable in the identification of novel antibacterial
      targets.

PMID- 25059765
TI  - Hepatic differentiation of human embryonic stem cells as microscaled multilayered
      colonies leading to enhanced homogeneity and maturation.
AB  - Directed differentiation of human embryonic stem cells (hESCs) towards hepatocyte
      like cells on planar tissue culture plates has been extensively investigated with
      great promise to provide alternative cell sources for drug metabolism/toxicity
      testing. Recently, hepatic differentiation of hESCs in 3D configuration with
      better mimicry of embryonic liver development represents incremental efforts to
      improve the differentiation efficiency and cellular maturation. However, most of
      the present 3D differentiation configurations involved interruptive operations
      during the multi-staged differentiation process, which might impose unwanted
      influence on cellular differentiation. Most of the current researches resulted in
      generation of hepatocytes with high expression of AFP, which is minimally
      expressed in primary hepatocytes. Here, off-the-shelf micro-stencil arrays are
      developed to generate adherent multilayered colonies composed of hESCs-derived
      cells. Uninterrupted cellular differentiation and proliferation is achieved to
      recapitulate the continuous and multi-stage liver development. Compared with
      conventional 2D format, the micro-scaled multilayered colonies with uniform and
      defined sizes constrained within the microwells are composed of more homogenous
      and mature hepatocyte-like cells with significantly lowered AFP expression and
      elevated hepatic functions. The multilayered colonies as novel 3D configuration
      for hepatic differentiation of hESCs represent a significant step toward
      efficient generation of functional hepatocytes for regenerative medicine and drug
      discovery. 

PMID- 25059763
TI  - Diverse and divergent protein post-translational modifications in two growth
      stages of a natural microbial community.
AB  - Detailed characterization of post-translational modifications (PTMs) of proteins
      in microbial communities remains a significant challenge. Here we directly
      identify and quantify a broad range of PTMs (hydroxylation, methylation,
      citrullination, acetylation, phosphorylation, methylthiolation, S-nitrosylation
      and nitration) in a natural microbial community from an acid mine drainage site.
      Approximately 29% of the identified proteins of the dominant Leptospirillum group
      II bacteria are modified, and 43% of modified proteins carry multiple PTM types.
      Most PTM events, except S-nitrosylations, have low fractional occupancy. Notably,
      PTM events are detected on Cas proteins involved in antiviral defense, an aspect
      of Cas biochemistry not considered previously. Further, Cas PTM profiles from
      Leptospirillum group II differ in early versus mature biofilms. PTM patterns are
      divergent on orthologues of two closely related, but ecologically differentiated,
      Leptospirillum group II bacteria. Our results highlight the prevalence and
      dynamics of PTMs of proteins, with potential significance for ecological
      adaptation and microbial evolution. 

PMID- 25059766
TI  - Preoperative magnetic resonance imaging for detecting uni- and bilateral
      extraprostatic disease in patients with prostate cancer.
AB  - OBJECTIVE: The objective of the study was to evaluate the diagnostic accuracy of
      preoperative magnetic resonance imaging (MRI) for detecting uni- and bilateral
      extraprostatic disease (T3) in patients with prostate cancer (PCa). MATERIALS AND
      METHODS: This prospective study included 199 patients with biopsy-proven PCa who
      underwent MRI prior to radical prostatectomy from December 2009 to July 2012.
      Extraprostatic extension and seminal vesicle invasion represented T3 disease, and
      was classified as uni- (right or left) or bilateral. MRI detection of T3 disease
      was assessed by descriptive statistics and odds ratio (OR). Whole-mount
      histopathology was used as the reference standard. RESULTS: The overall
      prevalence of pT3 was 105/199 (53 %), unilateral in 81/105 (77 %) and bilateral
      in 24/105 (23 %). The sensitivity of MRI for predicting pT3 was 76/105 (72 %),
      specificity 61/94 (65 %), accuracy 137/199 (69 %), and OR 4.8 (95 % CI 2.7-8.8).
      A complete match with respect to the laterality of pT3 was found in 52/105 (50
      %), and the side-specific accuracy was 113/199 (57 %). When unilateral pT3 was
      found, MRI falsely suggested contralateral T3 in 4/81 (5 %) and bilateral in 8/81
      (10 %). When bilateral pT3 was found, MRI falsely suggested unilateral T3 in
      12/24 (50 %). CONCLUSION: Magnetic resonance imaging (MRI) detected 72 % of all
      patients with T3 disease, and the accuracy dropped from 69 to 57 % when
      considering the laterality of T3. Thus far, the MRI technique is not yet adequate
      to meet the increasing demands of accurate diagnosis of locally advanced disease,
      and the contemporary MRI staging should be careful.

PMID- 25059767
TI  - [Stereotactic irradiation in head and neck cancers].
AB  - Stereotactic radiotherapy is increasingly used in head and neck tumours, either
      as a boost for dose escalation/early salvage, or in the reirradiation setting. We
      aimed to assess the level of evidence for each clinical setting and to discuss
      the different dose and frationation regimens. A search of the French and English
      literature was performed on PubMed until December 2013. Stereotactic
      reirradiation of locally recurrent squamous cell carcinomas can be performed with
      overall survival rates of about 12 months with good quality of life, and
      acceptable toxicity, based on several phase 2 trials and retrospective studies.
      Nasopharyngeal carcinomas may be irradiated with even better control rates. Late
      severe toxicities yield up to 20-30%. Patient and tumour selection criteria
      (limited volume) and dose constraints to the carotids (cumulative dose 110 Gy or
      less, to avoid the risk of potentially lethal carotid blowout) must be carefully
      chosen. Fractionated regimens (at least five fractions) should be preferred (30
      Gy in five fractions to 36 Gy in six fractions). Methods derived from
      stereotactic, intensity-modulated radiotherapy (IMRT) may be used with
      conventional fractionation for larger tumours. Stereotactic irradiation may be
      associated with cetuximab; data with chemotherapy or other targeted therapies are
      still lacking. Stereotactic irradiation is also used as a boost after 46 Gy IMRT
      in several institutions or for early salvage (8 to 10 weeks following full dose
      irradiation with evidence of residual tumour) in squamous or nasopharyngeal
      carcinomas. Such indications should be evaluated prospectively in clinical
      trials. Data in salivary gland and sinonasal neoplasms are still scarce. In
      conclusion, stereotactic body radiation therapy has the potential as a boost or
      in the reirradiation setting to improve local control in head and neck tumours.
      Careful hypofractionation with planning caring for the dose to the main vessels
      is highly recommended. Prospective studies with prolonged follow-up (at least 2
      years) should be encouraged.

PMID- 25059768
TI  - The influence of Ser-154, Cys-113, and the phosphorylated threonine residue on
      the catalytic reaction mechanism of Pin1.
AB  - Pin1 is an enzyme that specifically catalyzes the cis-trans isomerization of
      proline amide bonds in peptides that contain a phosphorylated threonine or serine
      residue in the position preceding proline. In the cell, the isomerization
      reaction is associated with cellular signaling and has been related to diseases
      such as Alzheimer and cancer. The catalytic mechanism by which Pin1 accelerates
      the isomerization reaction, however, is still unknown. In this study, we use
      molecular dynamics simulation in combination with the QM/MM methodology to
      disclose the influence of the residues Ser-154 and Cys-113 in the enzyme and the
      phosphorylated threonine residue in the peptide on the reaction mechanism. To
      account for the correct electrostatic interaction between the three residues and
      the reactive center, we derive atomic charges that account for the varying
      electrostatic field in the catalytic cavity. Different methods based on
      reproducing the molecular electrostatic potential or an atoms in molecules
      approach were investigated. Finally, the reaction mechanism is analyzed with the
      mean reaction force and the influence of the three residues is disclosed. Our
      results show that Pin1 specifically catalyzes the isomerization of the trans
      conformer in a jump-rope type of motion, as suggested by us and confirmed
      experimentally by others. This is accomplished by anchoring the threonine
      phosphate residue on one end of the peptide through electrostatic interactions
      with the basic triad of the enzyme and at the other end through specific enzyme
      peptide hydrogen bonds. Cys-113 reduces the structural contribution to the
      activation free energy through the stabilization of the cis conformer, and Ser
      154 in combination with Gln-131 assist in the isomerization reaction of the trans
      isomer. 

PMID- 25059770
TI  - Global myocardial contractile reserve assessed by high-dose dobutamine stress
      echocardiography predicts response to the cardiac resynchronization therapy.
AB  - BACKGROUND: Myocardial contractile reserve (CR) is a strong prognostic factor in
      patients with heart failure. The presence of significant myocardial fibrosis can
      lead to a reduced response to cardiac resynchronization therapy (CRT). We assumed
      that myocardial CR assessed by high-dose dobutamine stress echocardiography (DSE)
      would predict response to CRT. METHODS: Fifty-two consecutive symptomatic
      patients with heart failure (New York Heart Association [NYHA] class III), with
      depressed ejection fraction (EF) of the left ventricle (26.3 +/- 6.9%) and
      dyssynchronous contractions (QRS duration 149.8 +/- 23.8 msec) underwent DSE
      before CRT implantation. The difference in EF at rest and at peak (40 MUg/kg per
      minute) DSE indicated global CR. Responders to CRT were defined by a decrease in
      left ventricular end-systolic volume of >=15% and/or an increase in EF of >=5%
      after 6 months of CRT. RESULTS: During high-dose dobutamine infusion, responders
      (28 patients, 54%) showed a greater increase in EF compared with nonresponders
      (Delta 11 +/- 7% vs. Delta 2 +/- 9%, P = 0.007). CR correlated moderately with an
      improvement in EF after 6 months of CRT (r = 0.50, P = 0.0009). Furthermore,
      responders showed significant improvement in clinical status, evaluated by a
      reduction in NYHA functional class (-0.8 +/- 0.6 vs. 0.1 +/- 0.4, P = 0.02),
      compared with nonresponders. A 7% exercise-induced increase in EF yielded
      sensitivity of 79% and specificity of 87% in predicting the response to CRT after
      6 months. CONCLUSIONS: Myocardial CR assessed by high-dose DSE can play a
      potentially important role in identifying responders to CRT.

PMID- 25059769
TI  - Clinical and radiological dissociation of anti-TNF plus methotrexate treatment in
      early rheumatoid arthritis in routine care: results from the ABRAB study.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoinflammatory joint disease
      which leads to the destruction of joints and disability of the patients. Anti
      tumour necrosis factor (anti-TNF) drugs can halt radiological progression better
      than conventional DMARDs even in clinical non-responders. METHODS: The efficacy
      of anti-TNF plus methotrexate (MTX) treatment versus MTX monotherapy on clinical
      and radiological outcomes were compared in early rheumatoid arthritis (RA)
      patients in clinical practice by retrospective analysis of an observational
      cohort.49 early RA patients (group A) on first-line MTX monotherapy and 35 early
      RA patients (group B) on anti-TNF plus MTX treatment were selected from an
      observational cohort and evaluated retrospectively focusing on their first twelve
      months of treatment. Data on disease activity (DAS28) and functional status (HAQ
      DI) were collected three monthly. One-yearly radiological progression was
      calculated according to the van der Heijde modified Sharp method (vdHS). Clinical
      non-responder patients in both groups were selectively investigated from a
      radiological point of view. RESULTS: Disease activity was decreased and
      functional status was improved significantly in both groups. One-yearly
      radiological progression was significantly lower in group B than in group A. The
      percentage of patients showing radiological non-progression or rapid radiological
      progression demonstrated a significant advantage for group B patients. In
      addition non-responder patients in group B showed similar radiological results as
      responders, while a similar phenomenon was not observed in patients in group A.
      CONCLUSIONS: Clinical efficacy within our study was similar for tight-controlled
      MTX monotherapy as well as for combination treatment with anti-TNF and MTX.
      However MTX monotherapy was accompanied by more rapid radiological progression
      and less radiological non-progression. Anti-TNF plus MTX decreased radiological
      progression even in clinical non-responders supporting the advantage of anti-TNF
      plus MTX combination in dissociating clinical and radiological effects.

PMID- 25059771
TI  - NDM-1-producing Acinetobacter soli from Taiwan.

PMID- 25059772
TI  - Baby with a rash. Erythema multiforme.

PMID- 25059773
TI  - Commentary: hybrid electric vehicles: stealthily taking over roadways nationwide.

PMID- 25059774
TI  - Change of shift. My husband is a physician.

PMID- 25059775
TI  - Annals of Emergency Medicine Journal Club. Is it still cool to cool? Interpreting
      the latest hypothermia for cardiac arrest trial: answers to the March 2014
      Journal Club questions.

PMID- 25059776
TI  - Global emergency medicine journal club: social media responses to the march 2014
      annals of emergency medicine journal club on targeted temperature management.
AB  - In March 2014, Annals of Emergency Medicine continued a successful collaboration
      with an academic Web site, Academic Life in Emergency Medicine (ALiEM), to host
      another Global Emergency Medicine Journal Club session featuring the 2013 New
      England Journal of Medicine article "Targeted Temperature Management at 33
      degrees C (91.4 degrees F) Versus 36 degrees C (96.8 degrees F) After Cardiac
      Arrest" by Nielsen et al. This online journal club used Twitter conversations, a
      live videocast with the authors, and detailed discussions on the ALiEM Web site's
      comment section. This summary article details the community discussion, shared
      insights, and analytic data generated using this novel, multiplatform approach. 

PMID- 25059777
TI  - Images in emergency medicine. Young child with strabismus. Retinoblastoma.

PMID- 25059778
TI  - Upper extremity pseudoaneurysms thrombose more likely than currently believed.

PMID- 25059779
TI  - In reply.

PMID- 25059780
TI  - Extreme sporting events and transport-mitigating strategies: an Australian
      perspective.

PMID- 25059781
TI  - In reply.

PMID- 25059782
TI  - Recognition of subspecialty boards in emergency medicine. Policy statement.

PMID- 25059783
TI  - Definition of clinical ultrasonography. Policy statement.

PMID- 25059785
TI  - Dosimetric feasibility of stereotactic body radiation therapy as an alternative
      to brachytherapy for definitive treatment of medically inoperable early stage
      endometrial cancer.
AB  - PURPOSE: This study was designed to evaluate the dosimetric feasibility of
      definitive stereotactic body radiation therapy (SBRT) for the treatment of
      medically inoperable early stage endometrial cancer. METHODS: CT simulation scans
      from 10 medically inoperable early stage endometrial cancer patients previously
      treated with high dose-rate (HDR) intracavitary brachytherapy were used to
      generate Helical Tomotherapy (HT) plans using the IMRT mode with clinical target
      volumes (CTVs) that included the uterus plus cervix. A prescription dose of 34 Gy
      in 4 fractions was used. The SBRT dosimetry was compared to the 10 prior
      intracavitary brachytherapy plans normalized to a standard dose. Organs at risk
      (OARs) evaluated were the bladder, rectum, sigmoid, femoral heads, and other
      bowel, including both large and small bowel. The simulation CT and daily image
      guidance for 4 patients treated with this technique were evaluated to assess for
      interfraction variation in the uterine position and effects on dosimetry.
      RESULTS: Compared to intracavitary brachytherapy, HT SBRT produced significantly
      greater overall target coverage to the uterus, boost CTV, and PTV, with exception
      of the V150% of the uterus. HT SBRT significantly increased dose to the rectum,
      bowel, and femoral heads compared to intracavitary brachytherapy, though not
      outside of dose tolerance limits. Review of daily image guidance for patients
      treated with this technique demonstrated good reproducibility with a mean overlap
      index of 0.87 (range, 0.74 - 0.99). CONCLUSIONS: Definitive SBRT for medically
      inoperable early stage endometrial cancer appears to be a feasible treatment
      option. Future studies are warranted to evaluate long-term clinical outcomes with
      this technique, compared to HDR intracavitary brachytherapy.

PMID- 25059784
TI  - Genetic insulin resistance is a potent regulator of gene expression and
      proliferation in human iPS cells.
AB  - Insulin resistance is central to diabetes and metabolic syndrome. To define the
      consequences of genetic insulin resistance distinct from those secondary to
      cellular differentiation or in vivo regulation, we generated induced pluripotent
      stem cells (iPSCs) from individuals with insulin receptor mutations and age
      appropriate control subjects and studied insulin signaling and gene expression
      compared with the fibroblasts from which they were derived. iPSCs from patients
      with genetic insulin resistance exhibited altered insulin signaling, paralleling
      that seen in the original fibroblasts. Insulin-stimulated expression of immediate
      early genes and proliferation were also potently reduced in insulin resistant
      iPSCs. Global gene expression analysis revealed marked differences in both
      insulin-resistant iPSCs and corresponding fibroblasts compared with control iPSCs
      and fibroblasts. Patterns of gene expression in patients with genetic insulin
      resistance were particularly distinct in the two cell types, indicating
      dependence on not only receptor activity but also the cellular context of the
      mutant insulin receptor. Thus, iPSCs provide a novel approach to define effects
      of genetically determined insulin resistance. This study demonstrates that
      effects of insulin resistance on gene expression are modified by cellular context
      and differentiation state. Moreover, altered insulin receptor signaling and
      insulin resistance can modify proliferation and function of pluripotent stem cell
      populations.

PMID- 25059786
TI  - Incidence of additional primary malignancies in patients with pancreatic and
      gastrointestinal neuroendocrine tumors.
AB  - BACKGROUND: The incidence of secondary malignancies is increased in patients with
      malignant and premalignant conditions. Although neuroendocrine tumors (NET) are
      uncommon, their incidence is increasing. We evaluated the rate of additional
      malignancies in patients with NET. METHODS: Using the Surveillance, Epidemiology,
      and End Results (SEER) database, we identified a cohort of patients with
      pancreatic NET (PNET) or gastrointestinal NET (GINET). We determined the
      incidence of additional cancers diagnosed either before or after the diagnosis of
      PNET or GINET, by comparing these rates with the general population. Using
      multivariable regression, we evaluated factors that increased the risk of an
      additional malignancy. RESULTS: A cohort of 9,727 NET patients was identified. A
      total of 3,086 additional cancers occurred in 2,508 patients (25.8 %). The most
      common sites of additional malignancies included colorectal (21.1 %), prostate
      (14.5 %), breast (13.3 %), and lung (11.6 %). Among patients with PNET, the
      incidence of breast, lung, uterine, lymph, and pancreatic cancers was less than
      expected in the general population, whereas in patients with GINET, the observed
      incidence of nearly all malignancies exceeded that expected. Increasing age,
      marital status, and localized NET were associated with increased risk.
      CONCLUSION: Our study shows that the incidence of additional malignancies in
      patients with PNET and GINET is 25.8 %. Patients with GINET are at increased risk
      of additional malignancies, whereas patients with PNET have a decreased risk
      compared with the general population. More vigilant surveillance for secondary
      malignancies should be performed in patients with GINET. Studies investigating
      potential etiologic oncogenic pathways are warranted.

PMID- 25059787
TI  - Screening mammography following autologous breast reconstruction: an unnecessary
      effort.
AB  - BACKGROUND: Currently, no standard guidelines exist regarding routine screening
      imaging in breast cancer patients following autologous reconstruction. Concern
      over nonpalpable chest wall recurrence has prompted many to pursue screening
      imaging. We analyzed the pattern of locoregional recurrence (LRR) and yield of
      screening imaging and exam in these patients. METHODS: We performed a
      retrospective chart review of all patients who had mastectomy with autologous
      reconstruction between 2000 and 2009. Presentation of LRR and utility of imaging
      and breast exam were analyzed. Screening mammography was performed at the
      discretion of the treating physicians. RESULTS: A total of 615 patients were
      identified and follow-up data were available for 541. Median follow-up from time
      of reconstruction was 7 years. Twenty-seven patients developed a LRR (5.0 %).
      Among patients screened with mammography (n = 397), an abnormality led to 25
      biopsies in 25 patients, and 2 were malignant (8 %). Among patients receiving
      routine clinical exam (n = 537), an abnormality led to 77 biopsies in 66
      patients, and 30 were malignant (39 %). The median time from cancer surgery to
      LRR was 2.6 years. LRR was detected on clinical exam in 24 of 27 patients (88.9
      %). Screening mammography detected two recurrences that were palpable on follow
      up exam. One patient had an incidental chest wall recurrence found on PET/CT. In
      summary, 26 of 27 (96.3 %) patients had a clinically detectable LRR. CONCLUSIONS:
      Diligent surveillance with clinical breast exam is a reliable method of detecting
      LRR after autologous reconstruction, identifying 96.3 % of recurrences in our
      study. Our results do not support routine mammographic screening in this
      population.

PMID- 25059788
TI  - Tumor response ratio predicts overall survival in breast cancer patients treated
      with neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly used to treat locally
      advanced breast cancer. Pathologic complete response (pCR) predicts improved
      overall survival (OS); however, prognosis of patients with partial response
      remains unclear. We evaluated whether tumor response ratio (TRR) is a better
      predictor of OS than current staging methods. METHODS: Using the National
      Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified
      patients with stage I-III breast cancer who had NAC and pretreatment imaging at
      City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS
      were analyzed. TRR was calculated as residual in-breast disease divided by size
      on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4
      (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or
      TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and
      tested by the log-rank test. Cox regression was performed to evaluate
      associations between OS and TRR in a multivariable analysis while controlling for
      potential confounders. RESULTS: There were 218 eligible patients identified; 59
      (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS
      decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %),
      and TG (60 %). TRR was the only measure that significantly predicted OS (p =
      0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p =
      0.87) were not significant. TRR continued to be statistically significant by
      multivariable analysis (p = 0.016). CONCLUSIONS: TRR takes into account both
      pretreatment and residual disease and more accurately predicts OS than pathologic
      stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and
      OS in breast cancer patients undergoing NAC.

PMID- 25059789
TI  - Colon cancer lymph node evaluation among military health system beneficiaries: an
      analysis by race/ethnicity.
AB  - BACKGROUND: The number of lymph nodes examined during colon cancer surgery falls
      below nationally recommended guidelines in the general population, with Blacks
      and Hispanics less likely to have adequate nodal evaluation in comparison to
      Whites. The Department of Defense's (DoD) Military Health System (MHS) provides
      equal access to medical care for its beneficiaries, regardless of racial/ethnic
      background. This study aimed to investigate whether racial/ethnic treatment
      differences exist in the MHS, an equal-access medical care system. METHODS:
      Linked data from the DoD cancer registry and administrative claims databases were
      used and included 2,155 colon cancer cases. Multivariate logistic regression
      assessed the association between race/ethnicity and the number of lymph nodes
      examined (<12 and >=12) overall and for stratified analyses. RESULTS: No overall
      racial/ethnic differences in the number of lymph nodes examined was identified.
      Further stratified analyses yielded similar results, except potential
      racial/ethnic differences were found among persons with poorly differentiated
      tumors, where non-Hispanic Blacks tended to be less likely to have >=12 lymph
      nodes dissected (odds ratio 0.34; 95 % confidence interval 0.14-0.80; p = 0.01)
      compared with non-Hispanic Whites. CONCLUSION: Racial/ethnic disparities in the
      number of lymph nodes evaluated among patients with colon cancer were not
      apparent in an equal-access healthcare system. However, among poorly
      differentiated tumors there might be racial/ethnic differences in nodal yield,
      suggesting the possible effects of factors other than access to healthcare.

PMID- 25059790
TI  - Prognostic value of extracapsular invasion of axillary lymph nodes combined with
      peritumoral vascular invasion in patients with breast cancer.
AB  - BACKGROUND: Extracapsular invasion (ECI) of metastatic axillary lymph nodes has
      been associated with aggressive nodal disease but its prognostic role in breast
      cancer is unclear. The present study evaluated nodal ECI as a predictor of breast
      cancer recurrence. METHODS: We evaluated 154 women with histologically proven
      node-positive breast cancer who were diagnosed with invasive ductal carcinoma,
      and investigated the relationships between ECI and recurrences and other
      clinicopathological factors, particularly vascular invasion and the number of
      lymph node metastases. RESULTS: The presence of ECI at positive nodes was
      significantly associated with the number of positive nodes, and with disease
      recurrence and survival in univariate (but not multivariate) analysis.
      Interestingly, all ECI(+) patients with distant metastases in our series had
      peritumoral vascular invasion (PVI), which may have reflected systemic disease;
      ECI with PVI of the primary tumor strongly predicted recurrent disease and
      shorter survival. CONCLUSION: ECI of axillary metastases combined with PVI
      indicates high tumor aggressiveness. Patients with ECI and PVI may be considered
      for stronger adjuvant therapies because of their high risk for distant
      recurrences.

PMID- 25059791
TI  - Sentinel lymph node biopsy for melanoma: a plea to let the data speak.

PMID- 25059792
TI  - Surgical patterns of care in patients with invasive breast cancer treated with
      neoadjuvant systemic therapy and breast magnetic resonance imaging: results of a
      secondary analysis of TBCRC 017.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NCT) downstages advanced primary tumors,
      with magnetic resonance imaging (MRI) being the most sensitive imaging predictor
      of response. However, the impact of MRI evaluation on surgical treatment
      decisions in the neoadjuvant setting has not been well described. We report
      surgical patterns of care across 8 National Cancer Institute comprehensive cancer
      centers in women receiving both NCT and MRI to evaluate the impact of MRI
      findings on surgical planning. METHODS: Seven hundred seventy women from 8
      institutions received NCT with MRI obtained both before and after systemic
      treatment. Univariate and multivariate analyses of imaging, patient-, and tumor
      related covariates associated with choice of breast surgery were conducted.
      RESULTS: MRI and surgical data were available on 759 of 770 patients. A total of
      345 of 759 (45 %) patients received breast-conserving surgery and 414 of 759 (55
      %) received mastectomy. Mastectomy occurred more commonly in patients with
      incomplete MRI response versus complete (58 vs. 43 %) (p = 0.0003). On
      multivariate analysis, positive estrogen receptor status (p = 0.02), incomplete
      MRI response (p = 0.0003), higher baseline T classification (p < 0.0001), younger
      age (p < 0.0006), and institution (p = 0.003) were independent predictors of
      mastectomy. A statistically significant trend toward increasing use of mastectomy
      with increasing T stage at presentation (p < 0.0001) was observed in patients
      with incomplete response by MRI only. Among women with complete response on MRI,
      43 % underwent mastectomy. CONCLUSIONS: Within a multi-institutional cohort of
      women undergoing neoadjuvant treatment for breast cancer, MRI findings were not
      clearly associated with extent of surgery. This study shows that receptor status,
      T stage at diagnosis, young age, and treating institution are more significant
      determinants of surgical treatment choice than MRI response data.

PMID- 25059793
TI  - The effect of mental health on employment: evidence from Australian panel data.
AB  - To what extent does poor mental health affect employment outcomes? Answering this
      question involves multiple technical difficulties: two-way causality between
      health and work, unobservable confounding factors and measurement error in survey
      measures of mental health. We attempt to overcome these difficulties by combining
      10 waves of high-quality panel data with an instrumental variable model that
      allows for individual-level fixed effects. We focus on the extensive margin of
      employment, and we find evidence that a one-standard-deviation decline in mental
      health reduces employment by 30 percentage points. Further investigations suggest
      that this effect is predominantly a supply rather than a demand-side response and
      is larger for older than young workers.

PMID- 25059795
TI  - Biased self-perceptions of social competence and engagement in physical and
      relational aggression: the moderating role of peer status and sex.
AB  - This study sought to expand on prior research suggesting that children low in
      peer status who either over- or underestimate their social competence relative to
      others' reports are more likely to be aggressive (White and Kistner [2011].
      Journal of Abnormal Child Psychology, 39, 645-656). The curvilinear associations
      between social competence bias and two forms of aggression (physical and
      relational) were examined in a sample of 4th through 6th graders (n = 183);
      moderation by both sex and peer status (peer preference and popularity) also were
      tested. Social competence bias was operationally defined as the residual
      difference between child and teacher ratings of the child's social competence.
      Aggression and peer status were measured using peer nomination procedures. There
      was a significant curvilinear association between social competence bias and
      physical aggression moderated by both types of peer status. For low peer status
      children greater underestimation and overestimation of social competence was
      associated with higher physical aggression. The curvilinear association between
      social competence bias and relational aggression was moderated by both peer
      status and sex. Popular boys had higher rates of relational aggression when they
      had accurate, rather than biased, self-perceptions of social competence. However,
      for very highly preferred girls, a more extreme positive bias was associated with
      an exponential increase in relational aggression. Results are discussed in terms
      of implications for aggression theory and intervention.

PMID- 25059794
TI  - Withdrawal of BDNF from hippocampal cultures leads to changes in genes involved
      in synaptic function.
AB  - Neurotrophins play a crucial role in mediating neuronal survival and synaptic
      plasticity. A lack of trophic factor support in the peripheral nervous system
      (PNS) is associated with a transcription-dependent programmed cell death process
      in developing sympathetic neurons. While most of the attention has been on events
      culminating in cell death in the PNS, the earliest events that occur after
      trophic factor withdrawal in the central nervous system (CNS) have not been
      investigated. In the CNS, brain-derived neurotrophic factor (BDNF) is widely
      expressed and is released in an activity-dependent manner to shape the structure
      and function of neuronal populations. Reduced neurotrophic factor support has
      been proposed as a mechanism to account for changes in synaptic plasticity during
      neurodevelopment to aging and neurodegenerative disorders. To this end, we
      performed transcriptional profiling in cultured rat hippocampal neurons. We used
      a TrkB ligand scavenger (TrkB-FC ) to sequester endogenous neurotrophic factor
      activity from hippocampal neurons in culture. Using a high-density microarray
      platform, we identified a significant decrease in genes that are associated with
      vesicular trafficking and synaptic function, as well as selective increases in
      MAP kinase phosphatases. A comparison of these changes with recent studies of
      Alzheimer's disease and cognitive impairment in postmortem brain tissue revealed
      striking similarities in gene expression changes for genes involved in synaptic
      function. These changes are relevant to a wide number of conditions in which
      levels of BDNF are compromised.

PMID- 25059796
TI  - Isolation of methicillin-resistant Staphylococcus spp. from ready-to-eat fish
      products.
AB  - A hundred samples from ready-to-eat (RTE) fish products were examined for the
      presence and antimicrobial susceptibility of Staphylococcus spp. Staphylococci
      were isolated from 43% of these samples (n = 100). The identified species in the
      samples were Staphylococcus aureus (7%), Staphylococcus epidermidis (13%),
      Staphylococcus xylosus (12%), Staphylococcus sciuri (4%), Staphylococcus warneri
      (3%), Staphylococcus saprophyticus (2%), Staphylococcus schleiferi (1%) and
      Staphylococcus auricularis (1%). Two Staph. aureus (MRSA) isolates, three Staph.
      epidermidis (MRSE), five Staph. xylosus, four Staph. sciuri, one Staph.
      schleiferi and one Staph. saprophyticus isolates were resistant to oxacillin and
      all of them carried the mecA gene. The two MRSA isolates belonged to the spa
      types t316 (ST359) and t548 (ST5) and none of them was able to produce
      enterotoxins. Pulsed field gel electrophoresis for Staph. aureus and Staph.
      epidermidis isolates revealed 6 and 11 distinct PFGE types, respectively,
      reflecting diversity. The presence of methicillin-resistant staphylococci,
      especially MRSA and MRSE, in RTE fish products may constitute a potential health
      risk for consumers. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides the
      first data on the occurrence of methicillin-resistant Staphylococcus aureus and
      methicillin-resistant coagulase-negative staphylococci in salted and smoked fish
      products in Greece. These results are important and useful for Staphylococcus
      spp. risk assessment and management programmes for ready-to-eat fish products.

PMID- 25059797
TI  - Agreement and discrepancy between mother and child in the evaluation of
      children's anxiety symptoms and anxiety life interference.
AB  - This study explored the agreement and discrepancy between mother and child
      reports of children's anxiety symptoms and anxiety life interference. A large
      community sample of 1,065 Portuguese children aged between 7 and 14 years and
      their mothers completed a DSM-based anxiety symptoms scale. For a subsample of
      135 children with an anxiety disorder, additional data on children's anxiety life
      interference and maternal anxiety and depression symptoms were collected. The
      results showed that children generally reported higher levels of anxiety symptoms
      than their mothers. Overall, most correlations between mother and child reports
      of anxiety symptoms were significant but in the low to moderate range, with the
      strongest associations for symptoms of specific phobias and school phobia. In the
      subsample of children with an anxiety disorder, mothers reported higher levels of
      anxiety life interference than children, and the correlation between mother and
      child reports of anxiety life interference was significant but again modest in
      magnitude. Lastly, maternal anxiety was positively associated with the
      discrepancy between mother and child reports of anxiety symptoms. Together, the
      results of this study further underline the importance of a multi-informant
      approach in the evaluation of children's anxiety problems. 

PMID- 25059798
TI  - Movement propensity and ability correlate with ecological specialization in
      European land snails: comparative analysis of a dispersal syndrome.
AB  - Intra- and interspecific differences in movement behaviour play an important role
      in the ecology and evolution of animals, particularly in fragmented landscapes.
      As a consequence of rarer and generally more fragmented habitat, and because
      dispersal tends to disrupt benefits brought by local adaptation, theory predicts
      that mobility and dispersal should be counter-selected in specialists. Using
      experimental data and phylogenetic comparative tools, we analysed movement
      propensity and capacity, as well as dispersal-related phenotypic traits, in
      controlled conditions in 20 species of European land snails from the Helicoidea
      superfamily. Costs of movement in terrestrial gastropods are among the highest in
      animals, which make them a potentially powerful model to test these predictions.
      Habitat specialists were indeed less likely to cross a boundary between a
      familiar and an unfamiliar substrate than generalists. They also had smaller
      feet, after accounting for size. Furthermore, exploring specialists were slower
      than generalists and had more tortuous trajectories, leading them to stay closer
      to the familiar patch. Movement traits were generally evolutionary labile, but
      some were constrained by body size, a phylogenetically conserved trait. High
      specialization and low-dispersal ability are two traits often considered to
      increase species vulnerability to fragmentation, climate changes and extinction.
      This study confirms they should not be considered separately, due to their
      integration in a dispersal syndrome. Therefore, specialist species face double
      penalty under habitat loss and other environmental changes, making them more
      vulnerable to extinction and contributing to the biotic homogenization of
      communities. 

PMID- 25059799
TI  - EMG activity of finger flexor muscles and grip force following low-dose
      transcutaneous electrical nerve stimulation in healthy adult subjects.
AB  - Somatosensory stimulation modulates cortical and corticospinal excitability and
      consequently affects motor output. Therefore, low-amplitude transcutaneous
      electrical nerve stimulation (TENS) has the potential to elicit favorable motor
      responses. The purpose of the two presented pilot studies was to shed light on
      TENS parameters that are relevant for the enhancement of two desirable motor
      outcomes, namely, electromyographic (EMG) activity and contraction strength of
      the finger flexors and wrist muscles. In 5 and 10 healthy young adults (in Study
      I and Study II, respectively) TENS was delivered to the volar aspect of the
      forearm. We manipulated TENS frequency (150 Hz vs. 5 Hz), length of application
      (10, 20, and 60 min), and side of application (unilateral, right forearm vs.
      bilateral forearms). EMG amplitude and grip force were measured before (Pre),
      immediately after (Post), and following 15 min of no stimulation (Study I only).
      The results indicated that low-frequency bursts of TENS applied to the skin
      overlying the finger flexor muscles enhance the EMG activity of the finger
      flexors and grip force. The increase in EMG activity of the flexor muscles was
      observed after 20 min of stimulation, while grip force was increased only after 1
      h. The effects of uni- and bilateral TENS were comparable. These observations
      allude to a modulatory effect of TENS on the tested motor responses; however,
      unequivocal conclusions of the findings are hampered by individual differences
      that affect motor outcomes, such as in level of attention.

PMID- 25059800
TI  - Editorial--the global epidemic of obesity.

PMID- 25059801
TI  - Transmission of obesity-adiposity and related disorders from the mother to the
      baby.
AB  - The conventional aetiological model of obesity and diabetes proposes a genetic
      predisposition and a precipitation by an unhealthy adult lifestyle. This
      hypothesis was challenged by David Barker who proposed that the intrauterine
      environment influences the risk of non-communicable diseases (NCDs). The original
      idea was based on fetal undernutrition because lower birth weight was associated
      with a higher risk of diabetes and heart disease. However, soon it was clear that
      the association was U shaped, and that the increased risk in large babies was
      driven by maternal obesity and diabetes. A number of human and animal studies
      have refined our ideas of 'fetal programming', which is now thought to be related
      to acquired chemical changes in DNA (methylation), histones (acetylation and
      other) and the role of non-coding miRNAs. Maternal nutritional disturbances are
      the major programming stimulus, in addition to a deranged metabolism, infections,
      maternal stress, extreme atmospheric temperature, etc. The first demonstration of
      a link between fetal 'starvation' and future ill-health was in the Dutch Hunger
      Winter studies. In the prospective Pune Maternal Nutrition Study, we found that
      small and thin Indian babies were more adipose compared to larger English babies,
      and their higher risk of future diabetes was reflected in higher insulin and
      leptin and lower adiponectin concentrations in the cord blood. This phenotype was
      partly related to a deranged 1-carbon metabolism due to an imbalance in vitamin
      B12 (low) and folate (high) nutrition, which was also related to insulin
      resistance in the offspring. Maternal obesity and diabetes have made an
      increasing contribution to childhood obesity and diabetes at a young age. This
      was prominently shown in Pima Indians but is now obvious in all other
      populations. The best window of opportunity to prevent fetal programming of NCDs
      is in the periconceptional period. This is the period when gametogenesis,
      fertilisation, implantation, embryogenesis and placentation occur. Improving the
      nutrition and the health of young girls could make a substantial contribution to
      reducing the rapidly rising epidemic of NCDs in the world. This is referred to as
      'primordial' prevention.

PMID- 25059802
TI  - Fast growth of infants of overweight mothers: can it be slowed down?
AB  - Data from 3 recently completed studies were pooled and analyzed to answer the
      question whether breastfed infants of overweight/obese mothers show accelerated
      growth. It was shown that these infants gain weight faster than indicated by the
      WHO standards and that they grow significantly faster than infants of lean
      mothers. The question whether fast infant growth can be slowed down by lowering
      the protein content of formulas was examined. It was shown that formulas with a
      protein content that is just moderately above that of human milk support normal
      growth while significantly slowing down fast growth.

PMID- 25059803
TI  - Developmental programming and transgenerational transmission of obesity.
AB  - The global obesity pandemic is often causally linked to marked changes in diet
      and lifestyle, namely marked increases in dietary intakes of high-energy diets
      and concomitant reductions in physical activity levels. However, far less
      attention has been paid to the role of developmental plasticity and alterations
      in phenotypic outcomes resulting from environmental perturbations during the
      early-life period. Human and animal studies have highlighted the link between
      alterations in the early-life environment and increased susceptibility to obesity
      and related metabolic disorders in later life. In particular, altered maternal
      nutrition, including both undernutrition and maternal obesity, has been shown to
      lead to transgenerational transmission of metabolic disorders. This association
      has been conceptualised as the developmental programming hypothesis whereby the
      impact of environmental influences during critical periods of developmental
      plasticity can elicit lifelong effects on the physiology of the offspring.
      Further, evidence to date suggests that this developmental programming is a
      transgenerational phenomenon, with a number of studies showing transmission of
      programming effects to subsequent generations, even in the absence of continued
      environmental stressors, thus perpetuating a cycle of obesity and metabolic
      disorders. The mechanisms responsible for these transgenerational effects remain
      poorly understood; evidence to date suggests a number of potential mechanisms
      underpinning the transgenerational transmission of the developmentally programmed
      phenotype through both the maternal and paternal lineage. Transgenerational
      phenotype transmission is often seen as a form of epigenetic inheritance with
      evidence showing both germline and somatic inheritance of epigenetic
      modifications leading to phenotype changes across generations. However, there is
      also evidence for non-genomic components as well as an interaction between the
      developing fetus with the in utero environment in the perpetuation of programmed
      phenotypes. A better understanding of how developmental programming effects are
      transmitted is essential for the implementation of initiatives aimed at curbing
      the current obesity crisis.

PMID- 25059804
TI  - Developmental programming of appetite/satiety.
AB  - Obesity is often attributed to a Western lifestyle, a high-fat diet and decreased
      activity. While these factors certainly contribute to adult obesity, compelling
      data from our laboratory and others indicate that this explanation is
      oversimplified. Recent studies strongly argue that maternal/fetal under- or
      overnutrition predisposes the offspring to become hyperphagic and increases the
      risk of later obesity. Both infants small for gestational age (SGA) or infants
      born to obese mothers who consume a high-fat diet are at a markedly increased
      risk of adult obesity. Specific alterations in the fetal metabolic/energy
      environment directly influence the development of appetite regulatory pathways.
      Specifically, SGA infants demonstrate (1) impaired satiety and anorexigenic cell
      signaling, (2) enhanced cellular orexigenic responses, (3) programmed dysfunction
      of neuroprogenitor cell proliferation/differentiation, and (4) increased
      expression of appetite (NPY) versus satiety (POMC) neurons. In both hypothalamic
      tissue and ex vivo culture, SGA newborns exhibit increased levels of the nutrient
      sensor SIRT1, signifying reduced energy, whereas maternal high-fat-exposed
      newborns exhibit reduced levels of pAMPK, signifying energy excess. Via
      downstream regulation of bHLH neuroproliferation (Hes1) and neurodifferentiation
      factors (Mash1, Ngn3), neurogenesis is biased toward orexigenic and away from
      anorexigenic neurons, resulting in excess appetite, reduced satiety and
      development of obesity. Despite the developmental programming of appetite
      neurogenesis, the potential for neuronal remodeling raises the opportunity for
      novel interventions.

PMID- 25059805
TI  - Modulation of the blink reflex and P3 component of the startle response during an
      interoceptive challenge.
AB  - The blink reflex component of the startle response is potentiated during
      processing of exteroceptive unpleasant stimuli. In contrast, blink magnitudes are
      often inhibited during interoceptive challenges. We measured respiration, blink
      magnitudes, and the P3 component to the acoustic startle probes in 34
      participants while breathing against a mild resistance (mask-with-tubing)
      compared to breathing with no mask. Breathing through a mask with tubing resulted
      in increased inspiratory resistance as indicated by increased flow rate and tidal
      volume, a compensatory breathing pattern. Blink magnitudes to probes presented
      during the mask-with-tubing condition were inhibited compared to no-mask.
      Likewise, the probe P3 component was smaller during breathing through a mild
      resistance. These data suggest that startle inhibition during interoceptive
      challenges might be due to a shift in attention towards the mildly unpleasant
      interoceptive stimuli. 

PMID- 25059806
TI  - The effect of polyaromatic hydrocarbons on the spectral and photophysical
      properties of diaryl-pyrrole derivatives: an experimental and theoretical study.
AB  - A new class of diaryl-pyrrole derivatives of the polyaromatic hydrocarbons (PAH)
      benzene, naphthalene, anthracene and pyrene were synthesized in a multicomponent
      reaction under microwave irradiation and studied in solution at room (293 K) and
      low (77 K) temperature. The study includes a complete spectroscopic evaluation
      (singlet-singlet and triplet-triplet absorption, fluorescence and phosphorescence
      spectra) as well as photophysical evaluation (fluorescence, phosphorescence and
      triplet lifetimes together with fluorescence and triplet occupation and singlet
      oxygen sensitization quantum yields). From the above evaluation, a complete set
      of deactivation rate constants (kF, kIC and kISC) could be obtained. The study
      was further complemented with TDDFT calculations. It is shown that, with the
      exception of the anthracene derivative, the diaryl-pyrrole moiety strongly
      influences the spectral and photophysical properties of the PAH and that with the
      exception of the benzene derivative, the excited state internal conversion
      deactivation channel of the diaryl-pyrrole derivatives is higher than that of the
      PAH counterparts. 

PMID- 25059807
TI  - Thinking backwards can inform concerns about 'incomplete' data.
AB  - Ecologists often feel that they need complete data before they are able to advise
      or make decisions. Thinking backwards, an idea from mathematics, suggests that we
      need to focus on the desired outcome to tell us which way to go for practical
      solutions for our ecological ambitions. 

PMID- 25059808
TI  - Diagnosis of prolactinoma in two male-to-female transsexual subjects following
      high-dose cross-sex hormone therapy.
AB  - Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their
      physical bodies to the female sex. Doses are usually somewhat higher than those
      used by hypogonadal women receiving oestrogen replacement. Particularly in cases
      of self-administration of cross-sex hormones, doses may be very high. Oestrogens
      are powerful stimulators of synthesis and release of prolactin and serum
      prolactin levels are usually somewhat increased following oestrogen treatment.
      Prolactinomas have been reported in male-to-female transsexual persons, both
      after use of high and conventional doses of oestrogens but remain rare events. We
      report two new cases of prolactinomas in male-to-female transsexual persons, one
      in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment
      since the age of 23 years and another one in a 42 year old who had initiated
      oestrogen treatment at the age of 17 years. Their serum prolactin levels were
      strongly increased, and the diagnosis of a pituitary tumour was confirmed by
      imaging techniques. Both cases responded well to treatment with cabergoline
      treatment whereupon serum prolactin normalised. Our two cases are added to the
      three cases of prolactinomas in the literature in persons who had used
      supraphysiological doses of oestrogens.

PMID- 25059809
TI  - Acute acepromazine overdose: clinical effects and toxicokinetic evaluation.
AB  - INTRODUCTION: Acepromazine is a phenothiazine that is used exclusively in
      veterinary medicine for multiple purposes. Human overdoses are rarely reported
      and toxicokinetic data has never been reported. We present a case of intentional
      acepromazine overdose resulting in central nervous system and cardiovascular
      toxicity with confirmatory toxicokinetic data. CASE REPORT: A 54-year-old woman
      intentionally ingested 950 mg of her dog's acepromazine. Within 3 h of ingestion,
      she developed central nervous system and respiratory depression along with
      hypotension requiring non-invasive ventilation and vasopressors. Clinical
      toxicity resolved over the following 8 h. Serial plasma acepromazine levels were
      determined using gas chromatography/mass spectrometry. The initial acepromazine
      level (1-h post-ingestion) was 63 ng/ml. Follow-up levels at 8-, 10.5-, and 13.5
      h post-ingestion were 8.9 ng/ml, 7.6 ng/ml, and 6.3 ng/ml, respectively.
      DISCUSSION: Human acepromazine toxicity is rarely reported but results in
      clinical toxicity (central nervous system depression, respiratory depression,
      hypotension) are similar to other phenothiazines. Compared to other
      phenothiazines, it appears to have a short elimination half-life that may account
      for the brief duration of clinical toxicity with relatively rapid improvement. No
      significant human cardiac toxicity has been reported. Treatment is supportive.
      CONCLUSION: This case highlights the unique toxicity of acepromazine in
      demonstrating rapid improvement of severe toxicity within 8 h consistent with a
      short elimination half-life.

PMID- 25059810
TI  - Three difficult cases: the challenge of autoimmunity, immunodeficiency and
      recurrent infections in patients with Good syndrome.
AB  - Good syndrome (GS) is a rare, adult-acquired primary combined immunodeficiency
      syndrome arising in the context of previous or current thymoma. Patients with GS
      frequently develop recurrent sinopulmonary infections and are also at high risk
      of autoimmune manifestations, including skin conditions such as lichen planus. We
      report three middle-aged patients with GS complicated by multiple autoimmune and
      infectious manifestations. The combination of immunodeficiency, autoimmunity and
      recurrent infections seen in patients with GS continues to present a management
      challenge, particularly in patients with oral mucosal disease and recurrent
      candidiasis. Clinicians should be prompted to investigate an underlying
      immunodeficiency in patients with multiple autoimmune conditions and recurrent
      sinopulmonary infections. 

PMID- 25059811
TI  - Ultrasound-assisted synthesis, anticonvulsant activity, and docking study of
      indole-appended thiazolidin-4-ones.
AB  - Two series of novel indolyl thiazolidin-4-one derivatives 4a-j and 5a-j were
      obtained by an ecofriendly synthetic protocol by treating a mixture of Schiff's
      bases (0.01 mol) with thioglycolic acid or thiolactic acid (0.01 mol) and
      anhydrous zinc chloride in catalytic amount in DMF as solvent under ultrasound
      irradiation, using an ultrasound synthesizer with a synthetic solid probe. The
      structures of the synthesized compounds were confirmed by IR, (1) H NMR, (13) C
      NMR, MS, and elemental analysis. The anticonvulsant activity and neurotoxicity of
      the newly synthesized compounds were established by MES and sc-PTZ model and by
      rotarod test, respectively, in vivo using mouse models. The actophotometer was
      used for the screening of behavioral activity. The compounds exhibited promising
      anticonvulsant activity; especially, the compounds showed maximum protection in
      the MES model at a dose of 100 mg/kg. Further, docking studies of the synthesized
      compounds were performed against the sodium channel receptor and showed good
      binding interactions with the receptor. A computational study was carried out to
      highlight the pharmacophore distance mapping, log p determination, and
      pharmacokinetic parameters. 

PMID- 25059812
TI  - Cu3I7 trimer and Cu4I8 tetramer based cuprous iodide polymorphs for efficient
      photocatalysis and luminescent sensing: unveiling possible hierarchical assembly
      mechanism.
AB  - Solvothermal reactions of CuI, 1,4-diazabicyclo[2.2.2]octane (DABCO), and HI in
      an ethanol solution at 140  degrees C/150  degrees C for 7 days resulted in two
      24-membered-ring-based layered semiconducting iodocuprate open-network polymorphs
      formulated as [deDABCO]2[meDABCO]Cu11I17 (deDABCO = N,N'-diethyl-1,4
      diazabicyclo[2.2.2] octane and meDABCO = N-methyl-N'-ethyl-1,4
      diazabicyclo[2.2.2]octane). The deDABCO and meDABCO templates were in situ
      generated via alkylation of DABCO during solvothermal reactions. The formation of
      layered Cu11I17(6-) polymorphs can be rationalized via analyses of hierarchical
      building units. There are four hierarchical building units in polymorphs, namely,
      primary CuI3 triangle and CuI4 tetrahedron, secondary Cu3I7 trimer and Cu4I8
      tetramer, tertiary Cu6I12 hexamer, and quaternary Cu12I22 dodecamer. The trimeric
      Cu3I7 secondary building unit (SBU) is constructed by three edge-shared CuI4
      tetrahedra, while the tetrameric Cu4I8 SBU with an inversion center is formed by
      edge-shared two CuI3 triangles and two CuI4 tetrahedra. Two Cu3I7 SBUs are fused
      together via the sharing of two iodine atoms to form a Cu6I12 tertiary building
      unit (TBU), and two TBUs are further fused via the sharing of two iodine atoms
      into a Cu12I22 quaternary building unit (QBU). In colorless polymorph 1, each
      Cu3I7 SBU is connected to three neighbors via one Cu4I8 and two Cu6I12 linkers to
      form a 6,3-connected layer with 24-membered ring window. Different from 1, each
      Cu6I12 TBU in yellowish polymorph 2 is connected to four neighbors via two Cu4I8
      and two Cu12I22 linkers to form a (4,4) topological layer also with 24-membered
      ring window. These two compounds are very rare examples of copper halide
      polymorphs that exhibit similar local coordination geometries of copper(I) but
      different layered open networks. Electrical conductivity, band structure
      calculation, and UV-vis diffuse-reflectance spectrometry indicate that 1 and 2
      are potential semiconductor materials, and the performance on the photocatalytic
      degradation of organic pollutants upon UV-light irradiation reveals that both 1
      and 2 are highly efficient photocatalysts. Two polymorphs exhibit very similar
      green photoluminescence at room temperature in the solid state, and the study of
      the luminescent response to solvent on two polymorphs exhibits highly sensitive
      sensing of nitro explosives via quenching. 

PMID- 25059813
TI  - Fibrinogen concentrate for bleeding--a systematic review.
AB  - Fibrinogen concentrate as part of treatment protocols increasingly draws
      attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the
      potential to reduce bleeding, transfusion requirement and subsequently reduce
      morbidity and mortality. A systematic search for randomised controlled trials
      (RCTs) and non-randomised studies investigating fibrinogen concentrate in
      bleeding patients was conducted up to November 2013. We included 30 studies of
      3480 identified (7 RCTs and 23 non-randomised). Seven RCTs included a total of
      268 patients (165 adults and 103 paediatric), and all were determined to be of
      high risk of bias and none reported a significant effect on mortality. Two RCTs
      found a significant reduction in bleeding and five RCTs found a significant
      reduction in transfusion requirements. The 23 non-randomised studies included a
      total of 2825 patients, but only 11 of 23 studies included a control group. Three
      out of 11 found a reduction in transfusion requirements while mortality was
      reduced in two and bleeding in one. In the available RCTs, which all have
      substantial shortcomings, we found a significant reduction in bleeding and
      transfusions requirements. However, data on mortality were lacking. Weak evidence
      from RCTs supports the use of fibrinogen concentrate in bleeding patients,
      primarily in elective cardiac surgery, but a general use of fibrinogen across all
      settings is only supported by non-randomised studies with serious methodological
      shortcomings. It seems pre-mature to conclude whether fibrinogen concentrate has
      a routine role in the management of bleeding and coagulopathic patients. More
      RCTs are urgently warranted. 

PMID- 25059814
TI  - Colorectal peritoneal carcinomatosis treated with cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy: the experience of a tertiary Asian
      center.
AB  - INTRODUCTION: Compared with intravenous chemotherapy, cytoreductive surgery (CRS)
      and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve
      survival in patients with recurrent colorectal disease confined to the
      peritoneum. We report our experience with CRS and HIPEC for colorectal cancer
      patients with peritoneal carcinomatosis, evaluating prognostic factors for
      disease-free survival (DFS), overall survival (OS), and perioperative morbidity
      and mortality. METHODS: All patients who underwent CRS and HIPEC were included in
      our study. Clinical characteristics, operative data, and 30-day morbidity and
      mortality were collected and evaluated. RESULTS: Between January 2001 and
      December 2012, there were 35 consecutive patients who underwent CRS and HIPEC at
      our institution. Thirty-three patients (94%) had optimal cytoreduction. No 30-day
      mortality was reported, but 14 patients had postoperative complications. The
      median DFS was 9.4 months (95% confidence interval 5.5-18.7 months), and DFS at 1
      year, 3 years, and 5 years were 43.8%, 22.3%, and 22.3%, respectively. The median
      OS was calculated to be 27.1 months (95% confidence interval 15.3-39.1), and the
      OS at 1 year, 3 years, and 5 years were 83.7%, 38.2%, and 19.1%, respectively.
      CONCLUSION: CRS and HIPEC can provide survival benefit, with reasonable morbidity
      and mortality for Asian patients with peritoneal carcinomatosis from colorectal
      cancer. Patient selection and perioperative management of the patients are key to
      the success of the procedure.

PMID- 25059815
TI  - Surgically treated rectal cancer patients--outcomes at a tertiary care cancer
      hospital in Pakistan.
AB  - AIM: The aim of this study was to analyze our experience with rectal cancer
      patients who underwent surgical excision at our institution. METHODS: Data on 112
      rectal cancer patients who underwent surgical resection with total mesorectal
      excision, from January 2005 to December 2008, were evaluated retrospectively.
      RESULTS: We achieved an initial complete remission rate of 74.1%. Overall, 92.8%
      of patients had a complete total mesorectal excision. The overall survival
      analysis for all patients showed a 1-year survival rate of 98%, a 3-year survival
      rate of 82%, and a 5-year survival rate of 70%. We report a 41.9% rate of
      postoperative complications. The 1-, 3-, and 5-year survival rates for females
      were 100%, 90%, and 72%, respectively and for males, they were 90%, 80%, and 68%,
      respectively. Differences in overall survival by sex were not statistically
      significant (p > 0.05). Those patients who were treated with only surgery had the
      best outcomes with survival being worse in those treated with surgery and
      adjuvant therapy. Neoadjuvant treatment followed by surgery led to better
      results. CONCLUSION: We conclude that we have been successful in achieving high
      rates of curative resection, complete remission, and overall survival.
      Neoadjuvant and adjuvant chemotherapy significantly impact rates of remission.

PMID- 25059816
TI  - Experience and learning curve of retroperitoneal laparoscopic ureterolithotomy.
AB  - OBJECTIVE: This study was conducted to evaluate clinical experience and learning
      curve associated with laparoscopic ureterolithotomy performed for upper ureteral
      stones. MATERIALS AND METHODS: The medical data of 50 patients who had undergone
      retroperitoneal laparoscopic ureterolithotomy between June 2010 and March 2013
      were retrospectively analyzed. To assess the learning curve, patients were
      divided into two groups: Group A (the first 25 cases) and Group B (the last 25
      cases). In Group A, double J stents were placed in 17 patients, whereas in Group
      B 15 patients received double J stents. In Group A, three ports were placed in
      nine patients and four ports in 16 patients. In Group B, three ports were placed
      in 20 patients and five patients had four ports. The patients were compared
      according to demographics, operative time, stone size, complications, hospital
      stay, and transfusion. RESULTS: The mean age for Group A was 47.8 +/- 14.13 (21
      72) years and that for Group B was 44.2 +/- 14.98 (22-78) years. Mean operative
      times were 106.4 +/- 38 (55-210) minutes and 70.76 +/- 30.4 (30-180) minutes for
      Groups A and B, respectively (p < 0.05). The mean hospital stay was 7.12 +/- 4.47
      (3-22) days and 4.04 +/- 2.05 (2-12) days for Groups A and B, respectively (p <
      0.05). The mean stone size was 20.12 +/- 5.18 (12-30) mm and 19.44 +/- 4.44 (13
      28) mm for Groups A and B, respectively (p > 0.05). CONCLUSION: In our study, as
      staff experience (in performing laparoscopic retroperitoneal ureterolithotomy)
      increased, operative time, length of hospital stay, and complication rates have
      correspondingly declined.

PMID- 25059818
TI  - Comparative study on topical immunomodulatory and anti-inflammatory treatments
      for plasma cell vulvitis: long-term efficacy and safety.
AB  - BACKGROUND: Evidence on the treatment of plasma cell vulvitis (PCV) is scarce and
      comparative studies are lacking. OBJECTIVE: To assess and compare the
      effectiveness and safety, on a long-term basis, of three topical interventions
      for the treatment of PCV. METHODS: Retrospectively collected efficacy and safety
      data of a cohort of PCV patients treated with fusidic acid 2% and betamethasone
      valerate 0.1% cream fixed combination (FA/BM, 14 patients), clobetasol propionate
      0.05% ointment (CP, six patients) and tacrolimus 0.1% ointment (TC, four
      patients) at different regimens between January 2000 and June 2013 were analysed.
      Treatment outcome was assessed according to Investigator Global Assessment (i)
      symptoms and (ii) signs, at 12, 24 and 52 weeks. RESULTS: After 12 weeks, 85% of
      all patients achieved satisfactory improvement in PCV-related symptoms and
      maintained the improvement across a 52-week observation period. About 45%
      achieved a satisfactory result in clinical signs after 12 weeks, without further
      improvement during the following 9 months. No statistical differences in response
      were found among treatment groups at 12, 24 and 52 weeks. All study treatments
      were significantly more effective in improving PCV symptoms rather than clinical
      signs. With regard to treatment tolerability, one patient (7.1%) in FA/BM group
      and one (25%) in TC group discontinued the treatment due to local side-effects.
      CONCLUSIONS: CP, FA/BM and TC are effective and safe in treating PCV, inducing
      both a rapid improvement of the disease, notably of symptoms, and stabilizing its
      control.

PMID- 25059817
TI  - Preconceptual Folic Acid Use and Recurrence Risk Counseling for Congenital Heart
      Disease.
AB  - OBJECTIVE: Recurrence risk of congenital heart disease (CHD) in families with an
      affected first-degree relative is increased as compared with the general
      population. Advances in genetic testing and evidence that preconceptual folic
      acid supplementation may decrease risk of CHD warrant preventative counseling for
      at-risk families. Our goal was to document patterns of preconceptual folic acid
      supplementation and recurrence risk counseling in at-risk families in order to
      identify opportunities for improved preventative care. DESIGN: Mothers referred
      for a fetal echocardiogram were prospectively enrolled. Cases were defined as
      mothers deemed to be at higher risk of having an affected fetus with CHD given an
      affected parent or affected previous pregnancy with CHD. Controls were defined as
      mothers with no prenatal risk factors. Mothers completed a validated
      questionnaire assessing use of folic acid supplementation and receipt of
      recurrence risk counseling. Chi-square analyses were performed to analyze
      questionnaire responses and demographic data. RESULTS: A total of 314 subjects
      participated (controls = 216, cases = 98). Cases took preconceptual folic acid
      supplementation more often than controls (P < .001), but only 55% started
      preconceptually. Maternal advanced education and counseling (P < .001) were
      associated with preconceptual supplementation, whereas complexity of CHD in the
      relative was not. While 70% of cases received some recurrence risk counseling,
      those with advanced education and complex CHD in the affected relative were more
      likely to receive counseling. Few at-risk cases interacted with genetic services
      (19%). CONCLUSIONS: At-risk mothers with lower education are less likely to take
      preconceptual folic acid supplementation or receive recurrence risk counseling.
      Health care providers should proactively provide this information to all at-risk
      patients and develop collaborations with genetic services.

PMID- 25059819
TI  - In vitro validation and comparison of different software packages or algorithms
      for coronary bifurcation analysis using calibrated phantoms: implications for
      clinical practice and research of bifurcation stenting.
AB  - BACKGROUND: The accuracy and precision of quantitative coronary angiography (QCA)
      software dedicated for bifurcation lesions compared with conventional single
      vessel analysis remains unknown. Furthermore, comparison of different bifurcation
      analysis algorithms has not been performed. METHODS: Six plexiglas phantoms with
      18 bifurcations were manufactured with a tolerance < 10 um. The bifurcation
      angiograms were analyzed using Cardiovascular Angiography Analysis System (CAAS;
      Version 5.10, Pie Medical Imaging, Maastricht, The Netherlands) and QAngio XA
      (Version 7.3, Medis Medical Imaging System BV, Leiden, The Netherlands) software
      packages. RESULTS: Conventional single-vessel analysis underestimated the
      reference vessel diameter and percent diameter stenosis in the proximal main
      vessel while it overestimated these parameters in the distal main vessel and side
      branch. CAAS software showed better overall accuracy and precision than QAngio XA
      (with automatic Y- or T-shape bifurcation algorithm selection) for various
      phantom diameters including minimum lumen diameter (0.012 +/- 0.103 mm vs. 0.041
      +/- 0.322 mm, P = 0.003), reference vessel diameter (-0.050 +/- 0.043 mm vs.
      0.116 +/- 0.610 mm, P = 0.026), and % diameter stenosis (-0.94 +/- 4.07 % vs.
      1.74 +/- 7.49 %, P = 0.041). QAngio XA demonstrated higher minimal lumen
      diameter, reference vessel diameter, and % diameter stenosis when compared to the
      actual phantom diameters; however, the accuracy of these parameters improved to a
      similar level as CAAS when the sole T-shape algorithm in the QAnxio XA was used.
      CONCLUSION: The use of the single-vessel QCA method is inaccurate in bifurcation
      lesions. Both CAAS and QAngio XA (when the T shape is systematically used)
      bifurcation software packages are suitable for quantitative assessment of
      bifurcations.

PMID- 25059820
TI  - Recommendations for the ethical use and design of artificial intelligent care
      providers.
AB  - OBJECTIVE: This paper identifies and reviews ethical issues associated with
      artificial intelligent care providers (AICPs) in mental health care and other
      helping professions. Specific recommendations are made for the development of
      ethical codes, guidelines, and the design of AICPs. METHODS: Current developments
      in the application of AICPs and associated technologies are reviewed and a
      foundational overview of applicable ethical principles in mental health care is
      provided. Emerging ethical issues regarding the use of AICPs are then reviewed in
      detail. Recommendations for ethical codes and guidelines as well as for the
      development of semi-autonomous and autonomous AICP systems are described. The
      benefits of AICPs and implications for the helping professions are discussed in
      order to weigh the pros and cons of their use. RESULTS: Existing ethics codes and
      practice guidelines do not presently consider the current or the future use of
      interactive artificial intelligent agents to assist and to potentially replace
      mental health care professionals. AICPs present new ethical issues that will have
      significant ramifications for the mental health care and other helping
      professions. Primary issues involve the therapeutic relationship, competence,
      liability, trust, privacy, and patient safety. Many of the same ethical and
      philosophical considerations are applicable to use and design of AICPs in
      medicine, nursing, social work, education, and ministry. CONCLUSION: The ethical
      and moral aspects regarding the use of AICP systems must be well thought-out
      today as this will help to guide the use and development of these systems in the
      future. Topics presented are relevant to end users, AI developers, and
      researchers, as well as policy makers and regulatory boards.

PMID- 25059821
TI  - Detection of OvHV-2 from an outbreak of sheep associated malignant catarrhal
      fever from crossbred cattle of Southern India.
AB  - An outbreak of sheep associated malignant catarrhal fever in crossbred cattle in
      a village of Andhra Pradesh, southern India, affected thirteen adult cows and two
      calves from a population of forty animals. All the affected animals were died
      between December and January 2013-14. The clinical and gross postmortem findings
      were typical of MCF in Indian crossbred cattle. Migrating sheep flocks were
      suspected source of infection for the cattle. The diagnosis was confirmed by
      heminested PCR in all the affected cattle and the suspected sheep flock. The PCR
      provided evidence of ovine herpes virus type 2. 

PMID- 25059822
TI  - Vulnerability of ecosystems to climate change moderated by habitat intactness.
AB  - The combined effects of climate change and habitat loss represent a major threat
      to species and ecosystems around the world. Here, we analyse the vulnerability of
      ecosystems to climate change based on current levels of habitat intactness and
      vulnerability to biome shifts, using multiple measures of habitat intactness at
      two spatial scales. We show that the global extent of refugia depends highly on
      the definition of habitat intactness and spatial scale of the analysis of
      intactness. Globally, 28% of terrestrial vegetated area can be considered refugia
      if all natural vegetated land cover is considered. This, however, drops to 17% if
      only areas that are at least 50% wilderness at a scale of 48*48 km are considered
      and to 10% if only areas that are at least 50% wilderness at a scale of 4.8*4.8
      km are considered. Our results suggest that, in regions where relatively large,
      intact wilderness areas remain (e.g. Africa, Australia, boreal regions, South
      America), conservation of the remaining large-scale refugia is the priority. In
      human-dominated landscapes, (e.g. most of Europe, much of North America and
      Southeast Asia), focusing on finer scale refugia is a priority because large
      scale wilderness refugia simply no longer exist. Action to conserve such refugia
      is particularly urgent since only 1 to 2% of global terrestrial vegetated area is
      classified as refugia and at least 50% covered by the global protected area
      network.

PMID- 25059823
TI  - Lactobacillus acidophilus attenuates downregulation of DRA function and
      expression in inflammatory models.
AB  - Probiotics, including Lactobacilli, are commensal bacteria that have been used in
      clinical trials and experimental models for the prevention and treatment of
      diarrheal disorders. Our previous studies have shown that Lactobacillus
      acidophilus (LA) and its culture supernatant (CS) stimulated Cl(-)/HCO3 (-)
      exchange activity, acutely via an increase in the surface levels of downregulated
      in adenoma (DRA, SLC26A3) and in long-term treatments via increasing its
      expression involving transcriptional mechanisms. However, the role of LA in
      modulating DRA activity under inflammatory conditions is not known. Current in
      vitro studies using human intestinal epithelial Caco-2 cells examined the
      efficacy of LA or its CS in counteracting the inhibitory effects of interferon
      gamma (IFN-gamma) on Cl(-)/HCO3 (-) exchange activity. Pretreatment of cells with
      LA or LA-CS for 1 h followed by coincubation with IFN-gamma significantly
      alleviated the inhibitory effects of IFN-gamma on Cl(-)/HCO3 (-) exchange
      activity. In the in vivo model of dextran sulfate sodium-induced experimental
      colitis (3% in drinking water for 7 days) in C57BL/6J mice, administration of
      live LA (3 * 10(9) colony-forming units) via oral gavage attenuated colonic
      inflammation. LA administration also counteracted the colitis-induced decrease in
      DRA mRNA and protein levels. Efficacy of LA or its secreted soluble factors in
      alleviating inflammation and inflammation-associated dysregulation of DRA
      activity could justify their therapeutic potential in inflammatory diarrheal
      diseases. 

PMID- 25059824
TI  - Novel mechanisms and signaling pathways of esophageal ulcer healing: the role of
      prostaglandin EP2 receptors, cAMP, and pCREB.
AB  - Clinical studies indicate that prostaglandins of E class (PGEs) may promote
      healing of tissue injury e.g., gastroduodenal and dermal ulcers. However, the
      precise roles of PGEs, their E-prostanoid (EP) receptors, signaling pathways
      including cAMP and cAMP response element-binding protein (CREB), and their
      relation to VEGF and angiogenesis in the tissue injury healing process remain
      unknown, forming the rationale for this study. Using an esophageal ulcer model in
      rats, we demonstrated that esophageal mucosa expresses predominantly EP2
      receptors and that esophageal ulceration triggers an increase in expression of
      the EP2 receptor, activation of CREB (the downstream target of the cAMP
      signaling), and enhanced VEGF gene expression. Treatment of rats with
      misoprostol, a PGE1 analog capable of activating EP receptors, enhanced
      phosphorylation of CREB, stimulated VEGF expression and angiogenesis, and
      accelerated esophageal ulcer healing. In cultured human esophageal epithelial
      (HET-1A) cells, misoprostol increased intracellular cAMP levels (by 163-fold),
      induced phosphorylation of CREB, and stimulated VEGF expression. A cAMP analog
      (Sp-cAMP) mimicked, whereas an inhibitor of cAMP-dependent protein kinase A (Rp
      cAMP) blocked, these effects of misoprostol. These results indicate that the
      EP2/cAMP/protein kinase A pathway mediates the stimulatory effect of PGEs on
      angiogenesis essential for tissue injury healing via the induction of CREB
      activity and VEGF expression. 

PMID- 25059825
TI  - Tis7 deletion reduces survival and induces intestinal anastomotic inflammation
      and obstruction in high-fat diet-fed mice with short bowel syndrome.
AB  - Effective therapies are limited for patients with parenteral nutrition-dependent
      short bowel syndrome. We previously showed that intestinal expression of the
      transcriptional coregulator tetradecanoyl phorbol acetate-induced sequence 7
      (tis7) is markedly increased during the adaptive response following massive small
      bowel resection and tis7 plays a role in normal gut lipid metabolism. Here, we
      further explore the functional implications of tis7 deletion in intestinal lipid
      metabolism and the adaptive response following small bowel resection. Intestinal
      tis7 transgenic (tis7(tg)), tis7(-/-), and wild-type (WT) littermates were
      subjected to 50% small bowel resection. Mice were fed a control or a high
      saturated-fat (42% energy) diet for 21 days. Survival, body weight recovery,
      lipid absorption, mucosal lipid analysis, and the morphometric adaptive response
      were analyzed. Quantitative real-time PCR was performed to identify tis7
      downstream gene targets. Postresection survival was markedly reduced in high-fat,
      but not control, diet-fed tis7(-/-) mice. Decreased survival was associated with
      anastomotic inflammation and intestinal obstruction postresection. High-fat, but
      not control, diet-fed tis7(-/-) mice had increased intestinal IL-6 expression.
      Intestinal lipid trafficking was altered in tis7(-/-) compared with WT mice
      postresection. In contrast, high-fat diet-fed tis7(tg) mice had improved survival
      postresection compared with WT littermates. High-fat diet feeding in the setting
      of tis7 deletion resulted in postresection anastomotic inflammation and small
      bowel obstruction. Tolerance of a calorie-rich, high-fat diet postresection may
      require tis7 and its target genes. The presence of luminal fat in the setting of
      tis7 deletion promotes an intestinal inflammatory response postresection. 

PMID- 25059826
TI  - Interference of angiotensin II and enalapril with hepatic blood flow regulation.
AB  - Acute reduction of portal vein blood flow (Qpv) increases hepatic arterial
      perfusion (Qha) [the hepatic arterial buffer response (HABR)]. Angiotensin II (AT
      II) reduces Qpv, but its effect on HABR is not known. We explored interactions of
      AT-II and enalapril with hepatic blood flow regulation. Twenty healthy
      anesthetized pigs were randomized to receive AT-II (n = 8) from 5 to 61 ng/kg per
      min, enalapril (n = 8) from 3 to 24 MUg/kg per h, or saline (n = 4). HABR was
      assessed by occluding portal vein and expressed as 1) ratio between changes in
      Qha and Qpv, 2) hepatic arterial conductance (Cha). AT-II infusion increased mean
      arterial blood pressure from 74 (66-77) mmHg to 116 (109-130) mmHg (median, IQR;
      P < 0.0001) and decreased cardiac output, Qpv, and renal artery flow (-24%, -28%
      and -45%, respectively). The fraction of cardiac output of Qha, carotid, and
      femoral flows increased. With enalapril, blood pressure decreased, whereas
      cardiac output was maintained with flow redistribution favoring hepatic and renal
      arteries. In AT-II group, dQha/dQpv increased from 0.06 (0.03, 0.17) to 0.24
      (0.13, 0.31) (P = 0.002), but Cha during acute portal vein occlusion decreased
      from 4.3 (1.6, 6.6) to 2.9 (1.2, 3.7) ml/mmHg (P = 0.003). Both variables
      remained unchanged in the enalapril group and in controls. AT-II infusion reduces
      portal flow in parallel with cardiac output and induces a dose-dependent
      redistribution of flow, favoring brain, hepatic artery, and peripheral tissues at
      the expense of renal perfusion. During HABR, AT-II decreases Cha but increases
      Qha compensation, likely as result of increased hepatic arterial perfusion
      pressure. Enalapril had no effect on HABR. 

PMID- 25059827
TI  - Enteric dysbiosis promotes antibiotic-resistant bacterial infection: systemic
      dissemination of resistant and commensal bacteria through epithelial
      transcytosis.
AB  - Antibiotic usage promotes intestinal colonization of antibiotic-resistant
      bacteria. However, whether resistant bacteria gain dominance in enteric
      microflora or disseminate to extraintestinal viscera remains unclear. Our aim was
      to investigate temporal diversity changes in microbiota and transepithelial
      routes of bacterial translocation after antibiotic-resistant enterobacterial
      colonization. Mice drinking water with or without antibiotics were
      intragastrically gavaged with ampicillin-resistant (Amp-r) nonpathogenic
      Escherichia coli (E. coli) and given normal water afterward. The composition and
      spatial distribution of intestinal bacteria were evaluated using 16S rDNA
      sequencing and fluorescence in situ hybridization. Bacterial endocytosis in
      epithelial cells was examined using gentamicin resistance assay and transmission
      electromicroscopy. Paracellular permeability was assessed by tight junctional
      immunostaining and measured by tissue conductance and luminal-to-serosal dextran
      fluxes. Our results showed that antibiotic treatment enabled intestinal
      colonization and transient dominance of orally acquired Amp-r E. coli in mice.
      The colonized Amp-r E. coli peaked on day 3 postinoculation and was competed out
      after 1 wk, as evidenced by the recovery of commensals, such as Escherichia,
      Bacteroides, Lachnospiraceae, Clostridium, and Lactobacillus. Mucosal penetration
      and extraintestinal dissemination of exogenous and endogenous enterobacteria were
      correlated with abnormal epithelial transcytosis but uncoupled with paracellular
      tight junctional damage. In conclusion, antibiotic-induced enteric dysbiosis
      predisposes to exogenous infection and causes systemic dissemination of both
      antibiotic-resistant and commensal enterobacteria through transcytotic routes
      across epithelial layers. These results may help explain the susceptibility to
      sepsis in antibiotic-resistant enteric bacterial infection. 

PMID- 25059828
TI  - Chemical constitution and effect of extracts of tomato plants byproducts on the
      enteric viral surrogates.
AB  - Byproducts of tomato are known to include phenolic compounds but have not been
      studied in depth. In this study, the phenolic compositions of (stem, leaf, root,
      and whole plant) of two tomato cultivars, Pitenza and Floradade, were analyzed by
      HPLC-DAD. In parallel, the antiviral effects of crude extracts on viral
      surrogates, the bacteriophages MS2 and Av-05 were evaluated. The leaf extracts
      from the two varieties showed the highest concentration of phenolic compounds.
      The compounds identified were gallic acid, chlorogenic acid, ferulic acid, cafeic
      acid, rutin, and quercetin, and they represented 3174.3 and 1057.9 mg/100 g dried
      weight of the Pitenza and Floradade cultivars, respectively. MS2 and Av-05 titers
      at 5 mg/mL were reduced by 3.47 and 5.78 log10 PFU/mL and 3.78 and 4.93 log10
      PFU/mL by Pitenza and Floradade cultivar leaf extract, respectively. These
      results show that tomato extracts are natural sources of bioactive substances
      with antiviral activity.

PMID- 25059829
TI  - ACTN3 R577X polymorphism and long-term survival in patients with chronic heart
      failure.
AB  - BACKGROUND: Previous studies have shown the occurrence of actinin-3 deficiency in
      the presence of the R577X polymorphism in the ACTN3 gene. Our hypothesis is that
      this deficiency, by interfering with the function of skeletal muscle fiber, can
      result in a worse prognosis in patients with chronic heart failure. METHODS: A
      prospective cohort study was conducted from 2002 to 2004. The eligibility
      criteria included diagnosis of chronic heart failure stage C from different
      etiologies. We excluded all patients with concomitant disease that could be
      related to poor prognosis. ACTN3 rs1815739 (R577X) polymorphism was detected by
      high resolution melting analysis. Survival curves were calculated with the Kaplan
      Meier method and evaluated with the log-rank statistic. The relationship between
      the baseline variables and the composite end-point of all-cause death was
      assessed using a Cox proportional hazards survival model. RESULTS: A total of 463
      patients were included in this study. The frequency of the ACTN3 577X variant
      allele was 39.0%. The LVEF mean was 45.6 +/- 18.7% and the most common etiology
      of this study was hypertensive. After a follow-up of five years, 239 (51.6%)
      patients met the pre-defined endpoint. Survival curves showed higher mortality in
      patients carrying RX or XX genotypes compared with patients carrying RR genotype
      (p = 0.01). CONCLUSION: R577X polymorphism in the ACTN3 gene was independently
      associated with worse survival in patients with chronic heart failure. Further
      studies are necessary to ensure its use as a marker of prognosis for this
      syndrome.

PMID- 25059830
TI  - The role of echocardiography in the intraoperative management of the fetus
      undergoing myelomeningocele repair.
AB  - INTRODUCTION: Fetal surgery for myelomeningocele (MMC) results in better outcomes
      compared to postnatal treatment. However, risks are present. We describe our
      experience with intraoperative fetal echocardiography during repair of MMC and
      report on the management of serious cardiovascular events. MATERIAL AND METHODS:
      The subjects included fetuses with intent to repair MMC from January 2011 to
      February 2014. The protocol involved continuous echocardiography in a looping,
      sequential manner of systolic function, heart rate and tricuspid and mitral valve
      regurgitation. RESULTS: A total of 101 cases intended fetal MMC repair; 100
      completed surgery. Intraoperative ventricular dysfunction was present in 60% (20
      mild, 25 moderate, 15 severe). Heart rate <100 bpm was noted in 11 cases.
      Tricuspid valve regurgitation was present in 35% (26 mild, 7 moderate, 2 severe);
      mitral valve regurgitation was present in 19% (15 mild, 4 moderate). Serious
      cardiovascular events were experienced in 7 cases, which affected the conduct of
      surgery and/or outcome. In 4 of these, medications were given via the umbilical
      vein and external cardiac compressions were performed. Fetal echocardiography was
      used to gauge the efficacy of compressions and to guide resuscitation.
      DISCUSSION: Cardiovascular compromise is common during fetal surgery for MMC.
      Intraoperative fetal echocardiography is recommended as a growing number of
      centers contemplate offering this form of novel, but potentially risky, therapy.

PMID- 25059831
TI  - Bonding to oxide ceramics-laboratory testing versus clinical outcome.
AB  - OBJECTIVES: Despite a huge number of published laboratory bonding studies on
      dental oxide ceramics clinical long-term studies on resin bonded oxide ceramic
      restorations are rare. The purpose of this review is to present the best
      available clinical evidence for successful bonding of dental oxide ceramic
      restorations. METHODS: Clinical trials with resin-bonded restorations that had no
      or only limited mechanical retention and were made from alumina or zirconia
      ceramic were identified using an electronic search in PubMed database. Overall 10
      publications with clinical trials could be identified. Their clinical outcome was
      compared with that laboratory bond strength studies. RESULTS: Clinical data
      provide strong evidence that air-abrasion at a moderate pressure in combination
      with using phosphate monomer containing primers and/or luting resins provide long
      term durable bonding to glass-infiltrated alumina and zirconia ceramic under the
      humid and stressful oral conditions. SIGNIFICANCE: As simple and clinically
      reliable bonding methods to oxide ceramics exist, the rationale for development
      of alternative bonding methods might be reconsidered especially when these
      methods are more time consuming or require rather complicated and/or technique
      sensitive procedures.

PMID- 25059832
TI  - Molecular and cytogenetic analysis in stillbirth: results from 481 consecutive
      cases.
AB  - INTRODUCTION: The underlying causes of stillbirth are heterogeneous and in many
      cases unexplained. Our aim was to conclude clinical results from karyotype and
      quantitative fluorescence-polymerase chain reaction (QF-PCR) analysis of all
      stillbirths occurring in Stockholm County between 2008 and 2012. By screening a
      subset of cases, we aimed to study the possible benefits of chromosomal
      microarray (CMA) in the analysis of the etiology of stillbirth. METHODS: During
      2008-2012, 481 stillbirths in Stockholm County were investigated according to a
      clinical protocol including karyotype or QF-PCR analysis. CMA screening was
      performed on a subset of 90 cases, corresponding to all stillbirths from 2010
      without a genetic diagnosis. RESULTS: Chromosomal aberrations were detected by
      karyotype or QF-PCR analysis in 7.5% of the stillbirths. CMA analysis
      additionally identified two known syndromes, one aberration disrupting a known
      disease gene, and 26 variants of unknown significance. Furthermore, CMA had a
      significantly higher success rate than karyotyping (100 vs. 80%, p < 0.001).
      DISCUSSION: In the analysis of stillbirth, conventional karyotyping is prone to
      failure, and QF-PCR is a useful complement. We show that CMA has a higher success
      rate and aberration detection frequency than these methods, and conclude that CMA
      is a valuable tool for identification of chromosomal aberrations in stillbirth.

PMID- 25059834
TI  - Evaluation of a web-based portal to improve resident education by neonatology
      fellows.
AB  - BACKGROUND: Integration of web-based educational tools into medical training has
      been shown to increase accessibility of resources and optimize teaching. We
      developed a web-based educational portal (WBEP) to support teaching of pediatric
      residents about newborn medicine by neonatology fellows. OBJECTIVES: 1) To
      compare residents' attitudes about their fellow-led education in the NICU pre-
      and post-WBEP; including assessment of factors that impact their education and
      usefulness of teaching tools. 2) To compare fellow utilization of various
      teaching modalities pre- and post-WBEP. DESIGN/METHODS: We queried residents
      about their attitudes regarding fellow-led education efforts and various teaching
      modalities in the NICU and logistics potentially impacting effectiveness. Based
      on these data, we introduced the WBEP - a repository of teaching tools (e.g.,
      mock code cases, board review questions, journal articles, case-based discussion
      scenarios) for use by fellows to supplement didactic sessions in a faculty-based
      curriculum. We surveyed residents about the effectiveness of fellow teaching pre-
      and post-WBEP implementation and the type of fellow-led teaching modalities that
      were used. RESULTS: After analysis of survey responses, we identified that
      residents cited fellow level of interest as the most important factor impacting
      their education. Post-implementation, residents described greater utilization of
      various teaching modalities by fellows, including an increase in use of mock
      codes (14% to 76%, p<0.0001) and journal articles (33% to 59%, p=0.02).
      CONCLUSIONS: A web-based resource that supplements traditional curricula led to
      greater utilization of various teaching modalities by fellows and may encourage
      fellow involvement in resident teaching.

PMID- 25059833
TI  - (-)-Epigallocatechin gallate selectively inhibits adenosine diphosphate
      stimulated human platelet activation: suppression of heat shock protein 27
      phosphorylation via p38 mitogen-activated protein kinase.
AB  - (-)-Epigallocatechin gallate (EGCG) is a major component of green tea. It has
      been demonstrated that EGCG has an antithrombotic effect by inhibiting platelet
      aggregation. However, the detailed mechanisms underlying the effects of EGCG
      remain to be elucidated. The present study examined the effects of EGCG on human
      platelet activation by various stimulators and the exact underlying mechanisms.
      EGCG suppressed adenosine diphosphate (ADP)-stimulated platelet aggregation dose
      dependently between 30 and 70 uM. By contrast, EGCG failed to affect platelet
      aggregation stimulated by collagen, U46619 (a TP agonist) or ristocetin (an
      activator of GPIb/IX/V). EGCG attenuated the ADP-induced phosphorylation of p38
      mitogen-activated protein (MAP) kinase and heat shock protein 27 (HSP27). The ADP
      stimulated release of platelet-derived growth factor (PDGF)-AB and the soluble
      CD40 (sCD40) ligand was inhibited by EGCG. These findings suggest that EGCG
      selectively inhibits ADP-stimulated human platelet activation and that EGCG
      reduces the release of PDGF-AB and the sCD40 ligand due to suppressing HSP27
      phosphorylation via p38 MAP kinase.

PMID- 25059835
TI  - Self-assessment and goal-setting is associated with an improvement in
      interviewing skills.
AB  - PURPOSE: Describe the relationship between medical students' self-assessment and
      goal-setting (SAGS) skills and development of interviewing skills during the
      first-year doctoring course. METHOD: 157 first-year medical students completed
      three two-case standardized patient (SP) interviews. After each of the first two,
      students viewed videotapes of their interview, completed a SAGS worksheet, and
      reviewed a selected tape segment in a seminar. SAGS was categorized into good and
      poor quality and interviewing skills were rated by trained raters. RESULTS: SAGS
      improved over time (37% good week 1 vs. 61% good week 10). Baseline SAGS and
      interviewing skills were not associated. Initial SAGS quality was associated with
      change in interviewing skills - those with poor-quality SAGS demonstrated a
      decrease and those with good-quality SAGS demonstrated an increase in scores by
      17 weeks (ANOVA F=4.16, p=0.024). For students whose SAGS skills were good at
      both week 1 and 10, interviewing skills declined in weeks 1-10 and then increased
      significantly at week 17. For those whose SAGS remained 'poor' in weeks 1-10,
      interviewing skills declined in weeks 10-17. CONCLUSIONS: In general, the quality
      of students' SAGS improved over time. Poor baseline SAGS skills and failure to
      improve were associated with a decrease in interviewing skills at 17 weeks. For
      students with better SAGS, interviewing skills increased at week 17. Improvement
      in SAGS skills was not associated with improved interviewing skills.
      Understanding structured self-assessment skills helps identify student
      characteristics that influence progressive mastery of communication skills and
      therefore may inform curriculum and remediation tailoring.

PMID- 25059836
TI  - New web-based applications for mechanistic case diagramming.
AB  - The goal of mechanistic case diagraming (MCD) is to provide students with more in
      depth understanding of cause and effect relationships and basic mechanistic
      pathways in medicine. This will enable them to better explain how observed
      clinical findings develop from preceding pathogenic and pathophysiological
      events. The pedagogic function of MCD is in relating risk factors, disease
      entities and morphology, signs and symptoms, and test and procedure findings in a
      specific case scenario with etiologic pathogenic and pathophysiological sequences
      within a flow diagram. In this paper, we describe the addition of automation and
      predetermined lists to further develop the original concept of MCD as described
      by Engelberg in 1992 and Guerrero in 2001. We demonstrate that with these
      modifications, MCD is effective and efficient in small group case-based teaching
      for second-year medical students (ratings of ~3.4 on a 4.0 scale). There was also
      a significant correlation with other measures of competency, with a 'true' score
      correlation of 0.54. A traditional calculation of reliability showed promising
      results (alpha =0.47) within a low stakes, ungraded environment. Further, we have
      demonstrated MCD's potential for use in independent learning and TBL. Future
      studies are needed to evaluate MCD's potential for use in medium stakes
      assessment or self-paced independent learning and assessment. MCD may be
      especially relevant in returning students to the application of basic medical
      science mechanisms in the clinical years. 

PMID- 25059837
TI  - An in vitro and in vivo validation of a novel monitor for intracuff pressure in
      cuffed endotracheal tubes.
AB  - BACKGROUND: The clinical practice of pediatric anesthesiology has changed with
      increasing use of cuffed endotracheal tubes (cETTs) in infants and children. To
      limit the risk of tracheal mucosal damage, regular monitoring of intracuff
      pressure (CP) is necessary. This study evaluates the efficacy and accuracy of a
      novel syringe device that provides a digital readout of the CP. METHODS: The
      study was conducted in two phases. In phase 1, an in vitro study, cETTs of sizes
      4.0, 5.0, and 6.0 mm ID were placed into polyvinylchloride tubing of appropriate
      sizes. The cuffs were then inflated, and the CP was measured simultaneously using
      the syringe device and a manometer. In phase 2, an in vivo study on 200 pediatric
      patients, the syringe device and the manometer were simultaneously attached to
      the pilot balloon to measure the CP following endotracheal intubation.
      Statistical analysis included linear regression analysis and Bland-Altman
      comparison. RESULTS: Linear regression analysis of the in vitro study
      demonstrated an R2 value of 0.9989. Bias and precision were -1.92 +/- 0.62 with
      95% level of agreement (LOA) ranging from -3.13 to -0.72. For the in vivo study,
      the linear regression analysis demonstrated an R2 value of 0.9943. The bias and
      precision were -0.53 +/- 0.68 with 95% LOA ranging from -1.86 to 0.81.
      CONCLUSION: The study has demonstrated clinically acceptable correlation between
      the CPs obtained from the standard manometer and the syringe device both in vitro
      and in vivo. This device is a simple, reliable, portable, and affordable method
      to monitor CP.

PMID- 25059838
TI  - Antenatal micronutrient supplementation and third trimester cortisol and
      erythropoietin concentrations.
AB  - Antenatal iron and multiple micronutrient supplementation has been shown in
      randomized trials to improve birthweight, although mechanisms are unknown. We
      examined late pregnancy serum erythropoietin (EPO) and cortisol concentrations in
      relation to maternal micronutrient supplementation and iron status indicators
      (haemoglobin, serum ferritin, soluble transferrin receptor) in 737 rural Nepalese
      women to explore evidence of stress or anaemia-associated hypoxia. A double
      masked randomized control trial was conducted from December 1998 to April 2001 in
      Sarlahi, Nepal, in which women received vitamin A alone (as control), or with
      folic acid (FA), FA + iron, FA + iron + zinc and a multiple micronutrient
      supplement. In a substudy, we collected maternal blood in the first and third
      trimester for biochemical assessments. Generalized estimating equations linear
      regression analysis was used to examine treatment group differences. EPO was ~ 14
      17 mIU mL(-1) lower (P < 0.0001) in late pregnancy in groups receiving iron vs.
      the control group, with no difference in the FA-only group. Cortisol was 1.3 MUg
      dL(-1) lower (P = 0.04) only in the micronutrient supplement group compared with
      the control group. EPO was most strongly associated with iron status indicators
      in groups that did not receive iron, and in the non-iron groups cortisol was
      positively correlated with EPO (r = 0.15, P < 0.01) and soluble transferrin
      receptor (sTfR, r = 0.19, P < 0.001). In adjusted analyses, third trimester EPO
      was associated with a reduction in low birthweight, whereas cortisol was
      negatively associated with length of gestation and higher risk of preterm birth.
      Iron and multiple micronutrient supplementation may enhance birth outcomes by
      reducing mediators of maternal stress and impaired erythropoiesis.

PMID- 25059839
TI  - Thermal imaging evaluation of paravertebral block for mastectomy in high risk
      patient: case report.
AB  - Thoracic paravertebral block is the technique of injecting local anesthetic
      adjacent to the thoracic vertebra close to where the spinal nerves emerge from
      the intervertebral foramina. It is effective in treating acute and chronic pain
      of unilateral origin from the chest and abdomen. This technique causes pain
      relief with pulmonary function preservation and great hemodynamic stability. 66
      year old woman (156 cm, 80 kg, BMI 32) with chronic right heart failure,
      hypertension and obesity, on chronic oxygen therapy was presented for elective
      mastectomy due to breast cancer. She suffered from severe COPD and also bullous
      emphysema. FVC 1.59 l; FEV1 0.55 l; FEV1%FVC 34.6. The paravertebral block was
      performed using the multi-shot percutaneous technique with additional light
      general anesthesia. For confirmation, of proper analgesia range, control of
      temperature changes, using FLIR i7 infrared camera, was performed. Control photos
      were made 20 min after the blockade and then 10 min later. Infrared photo showed
      rise of temperature reading in every marked region. There were no hemodynamic and
      pulmonary complications postoperatively. Paravertebral block in combination with
      sedation creates excellent conditions for breast surgery procedures. Additional
      temperature changes monitoring performed with infrared camera may confirm proper
      range of analgesia needed to perform surgery. Great cardiovascular stability and
      very good pulmonary function preservation make this method excellent for high
      risk patients. Low complication rate is additional advantage. In our opinion this
      method is recommendable. 

PMID- 25059840
TI  - Defining 'medical necessity' in an age of personalised medicine: A view from
      Canada.
AB  - The concept of medical necessity plays a central role in many healthcare systems,
      including Canada's, by helping determine which healthcare services will receive
      funding. Despite its significance in health policy frameworks, medical necessity
      has proven to be notoriously difficult to define and operationalise. A shift
      toward a more personalised and genetically-informed approach to the provision of
      healthcare seems likely to heighten associated policy challenges. One of the
      stated goals of personalised medicine is to save healthcare systems money by
      facilitating the use of less and more effective treatments. However, any cost
      saving potential may ultimately be thwarted by physicians' legal and ethical
      obligations, given that physicians will inevitably be required to implement and
      define the bounds of genetically-informed medical necessity for their patients. 

PMID- 25059841
TI  - Podoplanin, E-cadherin, beta-catenin, and CD44v6 in recurrent ameloblastoma:
      their distribution patterns and relevance.
AB  - BACKGROUND: Ameloblastoma is a benign but locally infiltrative odontogenic
      epithelial neoplasm with a high risk for recurrence. Podoplanin, a lymphatic
      endothelium marker, putatively promotes collective cell migration and
      invasiveness in this neoplasm. However, its role in the recurrent ameloblastoma
      (RA) remains unclear. As morphological, signaling, and genetic differences may
      exist between primary and recurrent tumors, clarification of their distribution
      patterns is of relevance. MATERIALS AND METHODS: Podoplanin was examined
      immunohistochemically in conjunction with E-cadherin, beta-catenin, and CD44v6 in
      25 RA. Immunostaining according to tumor area, cellular type, and location, and
      relationship of these proteins were analyzed. Findings were compared with 25
      unrelated primary ameloblastomas (UPA). RESULTS: All four proteins were detected
      in RA and UPA samples. Expression rates for each protein were not significantly
      different between these two groups. RA demonstrated significant upregulation of
      podoplanin at the invasive front (P < 0.05), whereas upregulation of beta-catenin
      and CD44v6 and downregulation of E-cadherin at this site were not statistically
      significant (P > 0.05). Immunolocalization for all four proteins was
      predominantly membranous and less frequently cytoplasmic. Pre-ameloblast-like
      cells were podoplanin(+) /CD44v6(-), while stellate reticulum-like cells were
      podoplanin(-)/CD44v6(+). Acanthomatous, granular cell, and desmoplastic variants
      in both RA and UPA were podoplanin(-/low) but stained weak-to-moderate for E
      cadherin, beta-catenin, and CD44v6. Stromal fibroblasts and lymph channels were
      variably podoplanin-positive. CONCLUSIONS: Podoplanin, beta-catenin, and CD44v6
      upregulation at the tumor invasive fronts in RA and UPA supports a differential
      regulatory role by these molecules in mediating collective cell migration and
      local invasiveness. E-cadherin downregulation suggests altered cell adhesion
      function during tumor progression.

PMID- 25059842
TI  - Cosolvent, ions, and temperature effects on the structural properties of Cecropin
      A-Magainin 2 hybrid peptide in solutions.
AB  - Antimicrobial peptides are promising alternative to traditional antibiotics and
      antitumor drugs for the battle against new antibiotic resistant bacteria strains
      and cancer maladies. The study of their structural and dynamics properties at
      physiological conditions can help to understand their stability, delivery
      mechanisms, and activity in the human body. In this article, we have used
      molecular dynamics simulations to study the effects of solvent environment,
      temperature, ions concentration, and peptide concentration on the structural
      properties of the antimicrobial hybrid peptide Cecropin A-Magainin 2. In
      TFE/water mixtures, the structure of the peptide retained alpha-helix contents
      and an average hinge angle in close agreement with the experimental NMR and CD
      measurements reported in literature. Compared to the TFE/water mixture, the
      peptide simulated at the same ionic concentration lost most of its alpha-helix
      structure. The increase of peptide concentration at both 300 and 310 K resulted
      in the peptide aggregation. The peptides in the complex retained the initial N
      ter alpha-helix segment during all the simulation. The alpha-helix stabilization
      is further enhanced in the high salt concentration simulations. The peptide
      aggregation was not observed in TFE/water mixture simulations and, the peptide
      aggregate, obtained from the water simulation, simulated in the same conditions
      did dissolve within few tens of nanoseconds. The results of this study provide
      insights at molecular level on the structural and dynamics properties of the CA
      MA peptide at physiological and membrane mimic conditions that can help to better
      understand its delivery and interaction with biological interfaces.

PMID- 25059843
TI  - Serial changes of humor comprehension for four-frame comic Manga: an fMRI study.
AB  - Serial changes of humor comprehension evoked by a well organized four-frame comic
      Manga were investigated by fMRI in each step of humor comprehension. The neural
      substrates underlying the amusing effects in response to funny and mixed order
      manga were compared. In accordance with the time course of the four frames, fMRI
      activations changed serially. Beginning with the second frame (development
      scene), activation of the temporo-parietal junction (TPJ) was observed, followed
      by activations in the temporal and frontal areas during viewing of the third
      frame (turn scene). For the fourth frame (punch line), strong increased
      activations were confirmed in the medial prefrontal cortex (MPFC) and cerebellum.
      Interestingly, distinguishable activation differences in the cerebellum between
      funny and non-funny conditions were also found for the fourth frame. These
      findings suggest that humor comprehension evokes activation that initiates in the
      TPJ and expands to the MPFC and cerebellum at the convergence level. 

PMID- 25059844
TI  - Synergic effects of pregabalin-acetaminophen combination in somatic and visceral
      nociceptive reactivity.
AB  - BACKGROUND/AIMS: The present study investigates the effects of pregabalin (PGB),
      acetaminophen (ACET) and tenoxicam (TNX) administration in somatic and visceral
      nociception, using the tail flick test and the writhing test in mice. METHODS: In
      the tail flick test, the substances were administered orally and the latency time
      response was recorded 15, 30, 60, 90 and 120 min after administration. In the
      writhing test, pain responses were scored every 5 min during a 30-min period
      after intraperitoneal injection of diluted acetic acid. RESULTS: Our study
      demonstrated that oral administration of the combination PGB-ACET resulted in a
      stronger increase of latency reaction - statistically significant after 15 min
      compared to TNX and after 30 min compared to PGB in tail flick test. In the
      writhing test, the combination PGB-ACET, but also PGB-TNX, resulted in a stronger
      decrease of writhe numbers - statistically significant compared to the effects of
      the separate administration of each substance. This decrease was more intense in
      animals treated with the combination PGB-ACET than with PGB-TNX. CONCLUSION:
      These results suggest an antinociceptive activity which may be a consequence of
      the synergic action of the substances.

PMID- 25059845
TI  - Directly decoupled diffusion-ordered NMR spectroscopy for the analysis of
      compound mixtures.
AB  - For the analysis of compound mixtures by NMR spectroscopy, it is important to
      assign the different peaks to the individual constituents. Diffusion-ordered
      spectroscopy (DOSY) is often used for the separation of signals based on their
      self-diffusion coefficient. However, this method often fails in the case of
      signal overlap, which is a particular problem for (1)H-detected DOSY spectra.
      Herein, an approach that allows the acquisition of homonuclear broadband
      decoupled DOSY spectra without the introduction of an additional decoupling
      dimension, by instant decoupling during acquisition, is presented. It was
      demonstrated on a mixture of six alcohols, and the investigation of the binding
      of a dodecapeptide to membrane mimetics.

PMID- 25059846
TI  - Host iron status and iron supplementation mediate susceptibility to erythrocytic
      stage Plasmodium falciparum.
AB  - Iron deficiency and malaria have similar global distributions, and frequently co
      exist in pregnant women and young children. Where both conditions are prevalent,
      iron supplementation is complicated by observations that iron deficiency anaemia
      protects against falciparum malaria, and that iron supplements increase
      susceptibility to clinically significant malaria, but the mechanisms remain
      obscure. Here, using an in vitro parasite culture system with erythrocytes from
      iron-deficient and replete human donors, we demonstrate that Plasmodium
      falciparum infects iron-deficient erythrocytes less efficiently. In addition,
      owing to merozoite preference for young erythrocytes, iron supplementation of
      iron-deficient individuals reverses the protective effects of iron deficiency.
      Our results provide experimental validation of field observations reporting
      protective effects of iron deficiency and harmful effects of iron administration
      on human malaria susceptibility. Because recovery from anaemia requires transient
      reticulocytosis, our findings imply that in malarious regions iron
      supplementation should be accompanied by effective measures to prevent falciparum
      malaria. 

PMID- 25059848
TI  - Impact of surgical wait time on oncologic outcomes in upper urinary tract
      urothelial carcinoma.
AB  - BACKGROUND AND OBJECTIVES: To assess the effect of surgical wait time on the
      oncologic outcomes of patients with upper urinary tract urothelial carcinoma
      (UTUC), particularly in the ureter. METHODS: Using an optimal surgical wait time
      cutoff value of 30.5 days, we allocated patients to an early group or a late
      group. Cancer specific survival (CSS) and local/distant recurrence-free survival
      (RFS) rates were estimated using the Kaplan-Meier method. Factors influencing CSS
      and RFS after radical surgery were identified using Cox proportional hazards
      regression models. Subgroup analysis was performed on ureteral urothelial
      carcinoma using the same methods. RESULTS: Of the 138 UTUC patients, CSS and RFS
      were not significantly different between the two groups. However, subgroup
      analysis of the 80 patients with ureteral urothelial carcinoma showed that CSS
      and RFS were significantly higher in the early subgroup, and multivariate
      analysis showed that a surgical wait time of >1 month was an independent
      prognostic factor of CSS and RFS in ureteral urothelial carcinoma (P = 0.04 and P
      < 0.001). CONCLUSIONS: A surgical wait time of >1 month in ureteral urothelial
      carcinoma was found to be an independent prognostic factor of disease recurrence
      and cancer-specific mortality.

PMID- 25059847
TI  - Immunohistochemical profile of ductal adenocarcinoma of the prostate.
AB  - Ductal adenocarcinoma of the prostate (DAC) is considered to be an aggressive
      subtype of prostate cancer with greater risk of progression than acinar
      adenocarcinoma (AC). It has been debated whether DAC is a distinct subtype or a
      morphological variant of AC. Our aim was to examine the protein expression of DAC
      and to compare the results with AC. A tissue microarray was constructed from 60
      DAC and 46 AC matched by Gleason score. The slides were stained for 28
      immunomarkers (estrogen, progesterone and androgen receptor, prolactin, PSA,
      prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK,
      p63, p504s, c-myc, EGFR, Ki-67, p16, p21, p27, p53, PTEN, ERG, PAX-2, and PAX-8).
      HMWCK was positive in 8.5 % of DAC, but negative in all cases of AC (p = 0.045).
      p16 was positive in 53.3 % of DAC and in 26.1 % of AC (p = 0.005). p53 was
      positive in 42.4 % of DAC and 26.7 % of AC (p = 0.031). A distinct patchy
      positivity of CK20 was seen in 23.7 % of DAC, and this pattern was also seen in
      9.1 % of AC (p = 0.047). Villin was positive in 3.4 % of DAC while expression was
      negative in AC. Ki-67 labeling index was significantly higher in DAC than in AC
      (mean 9.2 % [95 % CI 6.4-12.0] and 2.6 % [1.9-3.4], p < 0.001). While there is
      some overlap in the immunohistochemical expression of DAC and AC, the differences
      between these two morphotypes of prostatic carcinoma are consistent with DAC
      having a more aggressive phenotype than AC.

PMID- 25059849
TI  - Editorial: Words hurt--avoiding dehumanizing language in orthopaedic research and
      practice.

PMID- 25059850
TI  - Systematic review of patient-specific instrumentation in total knee arthroplasty:
      new but not improved.
AB  - BACKGROUND: Patient-specific cutting blocks have been touted as a more efficient
      and reliable means of achieving neutral mechanical alignment during TKA with the
      proposed downstream effect of improved clinical outcomes. However, it is not
      clear to what degree published studies support these assumptions.
      QUESTIONS/PURPOSES: We asked: (1) Do patient-specific cutting blocks achieve
      neutral mechanical alignment more reliably during TKA when compared with
      conventional methods? (2) Does patient-specific instrumentation (PSI) provide
      financial benefit through improved surgical efficiency? (3) Does the use of
      patient-specific cutting blocks translate to improved clinical results after TKA
      when compared with conventional instrumentation? METHODS: We performed a
      systematic review in accordance with Cochrane guidelines of controlled studies
      (prospective and retrospective) in MEDLINE(r) and EMBASE(r) with respect to
      patient-specific cutting blocks and their effect on alignment, cost, operative
      time, clinical outcome scores, complications, and survivorship. Sixteen studies
      (Level I-III on the levels of evidence rubric) were identified and used in
      addressing the first question, 13 (Level I-III) for the second question, and two
      (Level III) for the third question. Qualitative assessment of the selected Level
      I studies was performed using the modified Jadad score; Level II and III studies
      were rated based on the Newcastle-Ottawa scoring system. RESULTS: The majority of
      studies did not show an improvement in overall limb alignment when PSI was
      compared with standard instrumentation. Mixed results were seen across studies
      with regard to the prevalence of alignment outliers when PSI was compared with
      conventional cutting blocks with some studies demonstrating no difference, some
      showing an improvement with PSI, and a single study showing worse results with
      PSI. The studies demonstrated mixed results regarding the influence of PSI on
      operative times. Decreased operative times were not uniformly observed, and when
      noted, they were found to be of minimal clinical or financial significance. PSI
      did reliably reduce the number of instrument trays required for processing
      perioperatively. The accuracy of the preoperative plan, generated by the PSI
      manufacturers, was found lacking, often leading to multiple intraoperative
      changes, thereby disrupting the flow of the operation and negatively impacting
      efficiency. Limited data exist with regard to the effect of PSI on postoperative
      function, improvement in pain, and patient satisfaction. Neither of the two
      studies we identified provided strong evidence to support an advantage favoring
      the use of PSI. No identified studies addressed survivorship of components placed
      with PSI compared with those placed with standard instrumentation. CONCLUSIONS:
      PSI for TKA has not reliably demonstrated improvement of postoperative limb or
      component alignment when compared with standard instrumentation. Although
      decisive evidence exists to support that PSI requires fewer surgical trays, PSI
      has not clearly been shown to improve overall surgical efficiency or the cost
      effectiveness of TKA. Mid- and long-term data regarding PSI's effect on
      functional outcomes and component survivorship do not exist and short-term data
      are scarce. Limited available literature does not clearly support any improvement
      of postoperative pain, activity, function, or ROM when PSI is compared with
      traditional instrumentation.

PMID- 25059851
TI  - Does advanced cryotherapy reduce pain and narcotic consumption after knee
      arthroplasty?
AB  - BACKGROUND: Cryotherapy has been used to enhance recovery after orthopaedic
      surgery. Several cooling devices are available but few can guarantee a fixed
      temperature during a prolonged time and therefore have been criticized. The
      arrival of new advanced cryotherapy devices made it possible to test the effect
      of prolonged cooling on rehabilitation after joint replacement.
      QUESTIONS/PURPOSES: The hypotheses of this randomized controlled trial (RCT) were
      that advanced cryotherapy devices compared with cold packs result in (1) better
      postoperative pain control resulting in a lower consumption of narcotics; (2)
      better early ROM; and (3) less postoperative bleeding and swelling. METHODS: A
      priori sample size calculation had determined that to detect a difference of 2
      points on the VAS, a sample size of 50 subjects per group at followup would be
      required, given a study power of 80%. One hundred sixteen patients were included
      and randomly allocated to receive advanced cryotherapy (n=58) or use of cold
      packs (n=58). The primary outcomes for the study were to evaluate pain with the
      VAS and analgesics consumption. Secondary outcomes were postoperative ROM,
      swelling, and blood loss. One hundred (50 in each group) patients had complete
      data available for analysis. RESULTS: No statistically significant differences in
      VAS, need for analgesics, nor in secondary outcomes were observed, except for
      substantially reduced flexion at 6 weeks in the advanced cryotherapy group (114
      degrees  versus 120 degrees ). CONCLUSIONS: Advanced cryotherapy with a
      continuous temperature for a prolonged period does not deliver expected results
      of superior early recovery after knee arthroplasty. Greater sample sizes are
      required to fully determine significant differences between the two techniques
      for these study parameters. Immobilization of the knee in extension during the
      prolonged cryotherapy session resulted in lower active flexion at 6 weeks after
      surgery for the advanced cryotherapy group. Advanced cryotherapy should not be
      used in fast track knee arthroplasty if the economic cost is higher than the
      price of cold packs or offers no other concomitant advantages. LEVEL OF EVIDENCE:
      Level II, therapeutic study. See the Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25059852
TI  - Apical and intermediate anchors without fusion improve Cobb angle and thoracic
      kyphosis in early-onset scoliosis.
AB  - BACKGROUND: The main goal of treatment in early-onset scoliosis is to obtain and
      maintain curve correction while simultaneously preserving spinal, trunk, and lung
      growth. This study introduces a new surgical strategy, called the modified
      growing rod technique, which allows spinal growth and lung development while
      controlling the main deformity with apical and intermediate anchors without
      fusion. The use of intraoperative traction at the initial procedure enables
      spontaneous correction of the deformity and decreases the need for forceful
      correction maneuvers on the immature spine and prevents possible implant
      failures. This study seeks to evaluate (1) curve correction; (2) spinal length;
      (3) number of procedures performed; and (4) complications with the new approach.
      DESCRIPTION OF TECHNIQUE: In the initial procedure, polyaxial pedicle screws were
      placed with a muscle-sparing technique. Rods were placed in situ after achieving
      correction with intraoperative skull-femoral traction. The most proximal and most
      distal screws were fixed and the rest of the screws were left with nonlocked set
      screws to allow vertical growth. The lengthening reoperations were performed
      every 6 months. METHODS: Between 2007 and 2011, we treated 19 patients surgically
      for early-onset scoliosis. Of those, 16 (29%) were treated with the modified
      growing rod technique by the senior author (AH); an additional three patients
      were treated using another technique that was being studied at the time by one of
      the coauthors (CO); those three were not included in this study. The 16 children
      included nine girls and seven boys (median, 5.5 years of age; range, 4-9 years),
      and all had progressive scoliosis (median, 64 degrees ; range, 38 degrees -92
      degrees ). All were available for followup at a minimum of 2 years (median, 4.5
      years; range, 2-6 years). RESULTS: The initial curve Cobb angle of 64 degrees 
      (range, 38 degrees -92 degrees ) improved to 21 degrees  (range, 4 degrees -36
      degrees ) and was maintained at 22 degrees  (range, 4 degrees -36 degrees )
      throughout followup. Preoperative thoracic kyphosis of 22 degrees  (range, 18
      degrees -46 degrees ) was maintained at 23 degrees  (range, 20 degrees -39
      degrees ) throughout followup without showing any substantial change. There was a
      47 mm (range, 38-72 mm) increase in T1-S1 height throughout followup. The mean
      number of lengthening operations was 5.5 (range, 4-10). The mean T1-S1 length
      gain from the first lengthening was 1.18 cm (range, 1.03-2.24 cm) and decreased
      to 0.46 cm (range, 0,33-1.1 cm) after the fifth lengthening procedure (p =
      0.009). The overall complication rate was 25% (four of 16 patients) and the
      procedural complication rate was 7% (seven of 102 procedures). We did not
      experience any rod breakages or other complications apart from two superficial
      wound infections managed without surgery during the treatment period. The only
      implant-related complications were loosening of two pedicle screws at the
      uppermost foundation in one patient. CONCLUSIONS: In this preliminary study, the
      modified growing rod technique with apical and intermediate anchors provided
      satisfactory curve control, prevented progression, maintained rotational
      stability, and allowed continuation of trunk growth with a low implant-related
      complication rate.

PMID- 25059853
TI  - Letter to the editor: Disc space preparation in transforaminal lumbar interbody
      fusion: a comparison of minimally invasive and open approaches.

PMID- 25059854
TI  - Role of gamma-aminobutyric acid signalling in the attenuation of counter
      regulatory hormonal responses after antecedent hypoglycaemia in healthy men.
AB  - The attenuated counter-regulatory response to hypoglycaemia after antecedent
      hypoglycaemic episodes has been observed in animals to be associated with an
      increase in gamma-aminobutyric acid (GABA) signalling. We therefore tested the
      hypothesis that the pharmacological suppression of GABAergic activity during a
      repeated hypoglycaemic episode enhances counter-regulatory responses. Fourteen
      healthy men participated in two experimental sessions each comprising three
      insulin-induced hypoglycaemic episodes. Before the third hypoglycaemic episode,
      participants received the GABA-antagonistic drug modafinil (200 mg orally) and
      placebo, respectively. In the placebo condition, the secretion of norepinephrine,
      adrenocorticotropic hormone, cortisol and growth hormone, and the perception of
      neuroglycopenic symptoms were attenuated during the third as compared with the
      first hypoglycaemic episode (each p < 0.05). Modafinil reversed this effect for
      the noradrenergic response (p < 0.05), while not significantly altering the
      attenuation of other hormonal responses and symptom perception (p > 0.3). Our
      findings indicate that increased GABAergic transmission could contribute to
      aspects of the attenuated counter-regulatory response after recurrent
      hypoglycaemia in humans.

PMID- 25059856
TI  - Complete Genome Sequence of Staphylococcus aureus XN108, an ST239-MRSA-SCCmec III
      Strain with Intermediate Vancomycin Resistance Isolated in Mainland China.
AB  - ST239-MRSA-SCCmec III (ST239, sequence type 239; MRSA, methicillin-resistant
      Staphylococcus aureus; SCCmec III, staphylococcal cassette chromosome mec type
      III) is the most predominant clone of hospital-acquired methicillin-resistant S.
      aureus in mainland China. We report here the complete genome sequence of XN108,
      the first vancomycin-intermediate S. aureus strain isolated from a steam-burned
      patient with a wound infection. 

PMID- 25059855
TI  - "Ballooning" patterns in takotsubo cardiomyopathy reflect different clinical
      backgrounds and outcomes: a BOREAS-TCM study.
AB  - Whether different patterns of ventricular ballooning in takotsubo cardiomyopathy
      (TCM) reflect differences in trigger mechanisms or clinical outcomes is unclear.
      Here we examined differences in the clinical characteristics of typical and
      atypical forms of TCM. TCM patients (n = 251) in the BOREAS Registry were
      enrolled for comparison of TCM with apical ballooning (type A, n = 217) and TCM
      with non-apical ballooning (type non-A, n = 34). The percentage of females was
      significantly lower in the type non-A group (58.8 vs. 75.6 %), while other
      demographic parameters and triggers of TCM were similar in the two groups. Rate
      of mid-ventricular obstruction (MVO) was lower (2.9 vs. 14.3 %) in the type non-A
      group than in the type A group, though left ventricular ejection fractions in the
      two groups were comparable. During a follow-up period of 2.6 +/- 2.8 years, TCM
      recurred in 2.9 % of the patients and cardiac death occurred in 4.0 %. Cox
      proportional hazard analysis indicated that body mass index (hazard ratio [HR]:
      0.75, 95 % confidence interval [CI] 0.54-0.99) and MVO (HR: 14.71, CI 1.87
      304.66) were determinants of TCM recurrence and that advanced age (HR: 1.09, CI
      1.02-1.17) and cardiogenic shock (HR: 4.27, CI 1.07-18.93) were significantly
      associated with cardiac death. In conclusion, approximately 20 % of TCM patients
      show non-apical left ventricular ballooning, and female sex and MVO are less
      frequent in this type than in apical ballooning type TCM. Low body mass index and
      MVO are risk factors of recurrence, and advanced age and cardiogenic shock are
      risk factors of cardiac death in TCM.

PMID- 25059857
TI  - Complete Genome Sequence of Coxsackievirus B1 Isolated during Case Outbreaks in
      2007 in the United States.
AB  - In 2007, clusters of severe coxsackievirus B1 (CVB1) infection occurred across
      the United States, and CVB1 became the most commonly reported enterovirus. The
      complete genome sequence of CVB1 isolated from an infant (CVB1-Chi07) was
      examined and found to be divergent from the Conn5 reference strain, with 80% and
      96% similarities at the nucleotide and amino acid levels, respectively. 

PMID- 25059858
TI  - Complete Sequencing and Chromosome-Scale Genome Assembly of the Industrial
      Progenitor Strain P2niaD18 from the Penicillin Producer Penicillium chrysogenum.
AB  - Penicillium chrysogenum is the major industrial producer of the beta-lactam
      antibiotic penicillin. Here, we report the complete genome sequence of the
      industrial progenitor strain P. chrysogenum P2niaD18 in a chromosome-scale genome
      assembly. P2niaD18 is distinguished from the recently sequenced P. chrysogenum
      Wisconsin 54-1255 strain by major chromosomal rearrangements leading to a
      modified chromosomal architecture. 

PMID- 25059859
TI  - Genome Sequence of Bacillus safensis CFA06, Isolated from Biodegraded Petroleum
      in Brazil.
AB  - Bacillus safensis is a microorganism recognized for its biotechnological and
      industrial potential due to its interesting enzymatic portfolio. Here, as a means
      of gathering information about the importance of this species in oil
      biodegradation, we report a draft genome sequence of a strain isolated from
      petroleum. 

PMID- 25059861
TI  - Draft Genome Sequence of Rickettsia aeschlimannii, Associated with Hyalomma
      marginatum Ticks.
AB  - Rickettsia aeschlimannii is a tick-associated human pathogen. We report here the
      draft genome of R. aeschlimannii strain MC16, isolated from Hyalomma marginatum
      marginatum ticks collected in Morocco. 

PMID- 25059860
TI  - Complete Genome Sequence of Staphylococcus xylosus HKUOPL8, a Potential
      Opportunistic Pathogen of Mammals.
AB  - We report here the first complete genome sequence of Staphylococcus xylosus
      strain HKUOPL8, isolated from giant panda feces. The whole genome sequence of
      this strain will provide an important framework for investigating the genes
      responsible for potential opportunistic infections with this species, as well as
      its survival in various environments. 

PMID- 25059862
TI  - Draft Genome Sequences of Two Marine Phototrophic Bacteria, Erythrobacter longus
      Strain DSM 6997 and Erythrobacter litoralis Strain DSM 8509.
AB  - Aerobic anoxygenic phototrophic bacteria (AAPB) are important functional groups
      and are widely distributed in the global upper ocean. Here we report the draft
      genomic sequences of two marine AAPB isolates belonging to the genus
      Erythrobacter, Erythrobacter longus strain DSM 6997 and Erythrobacter litoralis
      strain DSM 8509. 

PMID- 25059863
TI  - Complete Genome Sequence of the Model Rhizosphere Strain Azospirillum brasilense
      Az39, Successfully Applied in Agriculture.
AB  - We present the complete genome sequence of Azospirillum brasilense Az39, isolated
      from wheat roots in the central region of Argentina and used as inoculant in
      extensive and intensive agriculture during the last four decades. The genome
      consists of 7.39 Mb, distributed in six replicons: one chromosome, three
      chromids, and two plasmids. 

PMID- 25059864
TI  - Rapid detection of trichodysplasia spinulosa-associated polyomavirus in skin
      biopsy specimen.
AB  - Trichodysplasia spinulosa-associated polyomavirus (TSV) is responsible for a rare
      skin cancer. Using metagenomic approaches, we determined the complete genome
      sequence of a TSV first detected in Brazil in spicules of an immunocompromised
      patient suspected to have trichodysplasia spinulosa. 

PMID- 25059865
TI  - Draft Genome Sequence of Marine Cyanobacterium Synechococcus sp. Strain
      NKBG042902, Which Harbors a Homogeneous Plasmid Available for Metabolic
      Engineering.
AB  - The marine cyanobacterium Synechococcus sp. strain NKBG042902 was isolated from
      coastal areas in Japan. Strain NKBG042902 has four plasmids: pSY8, pSY9, pSY10,
      and pSY11. Moreover, the hybrid plasmid pUSY02 containing pSY11 and Escherichia
      coli plasmid pUC18 was constructed for this strain. The genetic manipulation
      technique using pUSY02 was established for this strain and used in metabolic
      engineering. Here, we report the draft genome sequence of this strain, which has
      77 contigs comprising a total length of 3,319,479 bp, with a G+C content of
      49.4%. 

PMID- 25059866
TI  - Characterization of the Whole-Genome Sequence of a Beak and Feather Disease Virus
      Isolate from a Mallee Ringneck Parrot (Barnardius zonarius barnardi).
AB  - The complete genome sequence of beak and feather disease virus (BFDV) from a wild
      Australian Mallee ringneck parrot (Barnardius zonarius barnardi) was
      characterized. The genome consists of 1,995 nucleotides and encodes two major
      proteins in opposing directions. This is the first evidence of BFDV infectivity
      and the first complete genome sequence for this novel host. 

PMID- 25059867
TI  - Whole-Genome Sequence of CMY-2 beta-Lactamase-Producing Salmonella enterica
      Serovar Typhimurium Strain L-3553.
AB  - Salmonella enterica serovar Typhimurium pulsed-field gel electrophoresis cluster
      VII has been isolated from cattle populations in Japan since the mid-2000s. Some
      cluster VII isolates exhibited extended-spectrum cephalosporin resistance defined
      by the blaCMY-2 gene located in a chromosomal genomic island, GI-VII-6. We
      determined the whole-genome sequence of strain L-3553 as the reference strain. 

PMID- 25059868
TI  - Genome Sequences of Cupriavidus metallidurans Strains NA1, NA4, and NE12,
      Isolated from Space Equipment.
AB  - Cupriavidus metallidurans NA1, NA4, and NE12 were isolated from space and
      spacecraft-associated environments. Here, we report their draft genome sequences
      with the aim of gaining insight into their potential to adapt to these
      environments. 

PMID- 25059869
TI  - Genome Sequence of a Newly Isolated Nicotine-Degrading Bacterium, Ochrobactrum
      sp. SJY1.
AB  - Ochrobactrum sp. SJY1 uses nicotine as the sources of carbon, nitrogen, and
      energy. The genome of SJY1 was sequenced in order to provide insights into its
      mechanism of nicotine degradation. Physiological characteristics and genome
      analysis indicate that strain SJY1 might have a different nicotine degradation
      pathway from the pyridine or pyrrolidine pathway. 

PMID- 25059870
TI  - Draft Whole Genome Sequence of Bacillus pumilus Strain 3-19, a Chemical Mutant
      Overproducing Extracellular Ribonuclease.
AB  - Here, we present a draft genome sequence of Bacillus pumilus strain 3-19. It was
      derived from soil-isolated B. pumilus 7P using chemical mutagenesis and is
      characterized by elevated production of extracellular ribonuclease which is known
      to possess different biological activities with potential of applications in
      experimental research, medicine, and biotechnology. 

PMID- 25059871
TI  - Improved Draft Genome Sequence of Probiotic Strain Lactobacillus gasseri K7.
AB  - Lactobacillus gasseri K7 is an isolate from infant feces and has in vitro and in
      vivo established probiotic properties. Here, we report the improved version of
      the draft genome sequence, which comprises 8 scaffolds (13 contigs), a total
      length of 1.99 Mb, and 1,841 predicted protein-coding sequences. 

PMID- 25059872
TI  - Draft Genome Sequence of the Multidrug-Resistant Clinical Isolate Dermabacter
      hominis 1368.
AB  - Dermabacter hominis is a common colonizer of the healthy human skin and is rarely
      detected as an opportunistic human pathogen. The genome sequence of the multidrug
      resistant D. hominis strain 1368, isolated from blood cultures of a
      pyelonephritis patient, provides insights into the repertoire of antibiotic
      resistance genes. 

PMID- 25059873
TI  - Draft Genome Sequence of Listeria monocytogenes Strain LI0521 (syn. HPB7171),
      Isolated in 1983 during an Outbreak in Massachusetts Caused by Contaminated
      Cheese.
AB  - Listeria monocytogenes, a pathogenic food-borne bacterium, is the causative agent
      of both sporadic and outbreak cases of human listeriosis. Here, we present the
      genome sequence of L. monocytogenes reference strain LI0521, isolated during an
      outbreak involving contaminated cheese, which has been used as the model during
      several proteomic studies. 

PMID- 25059874
TI  - Draft Genome Sequence of Komagataeibacter rhaeticus Strain AF1, a High Producer
      of Cellulose, Isolated from Kombucha Tea.
AB  - Here, we present the draft genome sequence of Komagatabaeicter rhaeticus strain
      AF1, which was isolated from Kombucha tea and is capable of producing high levels
      of cellulose. 

PMID- 25059875
TI  - Draft Genome Sequence of Bacillus amyloliquefaciens EBL11, a New Strain of Plant
      Growth-Promoting Bacterium Isolated from Rice Rhizosphere.
AB  - Bacillus amyloliquefaciens strain EBL11 is a bacterium that can promote plant
      growth by inhibiting the growth of fungi on plant surfaces and providing
      nutrients as a nonchemical biofertilizer. The estimated genome of this strain is
      4.05 Mb in size and harbors 3,683 coding genes (CDSs). 

PMID- 25059876
TI  - Draft Genome Sequence of Kluyveromyces marxianus Strain DMB1, Isolated from
      Sugarcane Bagasse Hydrolysate.
AB  - We determined the genome sequence of a thermotolerant yeast, Kluyveromyces
      marxianus strain DMB1, isolated from sugarcane bagasse hydrolysate, and the
      sequence provides further insights into the genomic differences between this
      strain and other reported K. marxianus strains. The genome described here is
      composed of 11,165,408 bases and has 4,943 protein-coding genes. 

PMID- 25059877
TI  - Draft Genome Sequence of Lutibaculum baratangense Strain AMV1T, Isolated from a
      Mud Volcano in Andamans, India.
AB  - The 4.3-Mb genome of Lutibaculum baratangense strain AMV1(T), isolated from a
      soil sample collected from a mud volcano in Andamans, India, is reported. The
      draft genome of strain Lutibaculum baratangense AMV1(T) consists of 4,300,776 bp
      with a G+C content of 66.93 mol% and 4,198 predicted coding regions, including 56
      RNAs. 

PMID- 25059878
TI  - Reduced aggregation and cytotoxicity of amyloid peptides by graphene oxide/gold
      nanocomposites prepared by pulsed laser ablation in water.
AB  - A novel and convenient method to synthesize the nanocomposites combining graphene
      oxides (GO) with gold nanoparticles (AuNPs) is reported and their applications to
      modulate amyloid peptide aggregation are demonstrated. The nanocomposites
      produced by pulsed laser ablation (PLA) in water show good biocompatibility and
      solubility. The reduced aggregation of amyloid peptides by the nanocomposites is
      confirmed by Thioflavin T fluorescence and atomic force microscopy. The cell
      viability experiments reveals that the presence of the nanocomposites can
      significantly reduce the cytotoxicity of the amyloid peptides. Furthermore, the
      depolymerization of peptide fibrils and inhibition of their cellular cytotoxicity
      by GO/AuNPs is also observed. These observations suggest that the nanocomposites
      combining GO and AuNPs have a great potential for designing new therapeutic
      agents and are promising for future treatment of amyloid-related diseases. 

PMID- 25059879
TI  - Pulmonary reversed halo sign as a presenting manifestation of rheumatoid
      arthritis.

PMID- 25059880
TI  - Is there a role for imatinib mesylate in the treatment of eosinophilic
      granulomatosis with polyangiitis?

PMID- 25059881
TI  - Intervention randomized controlled trials involving wrist and shoulder
      arthroscopy: a systematic review.
AB  - BACKGROUND: Although arthroscopy of upper extremity joints was initially a
      diagnostic tool, it is increasingly used for therapeutic interventions.
      Randomized controlled trials (RCTs) are considered the gold standard for
      assessing treatment efficacy. We aimed to review the literature for intervention
      RCTs involving wrist and shoulder arthroscopy. METHODS: We performed a systematic
      review for RCTs in which at least one arm was an intervention performed through
      wrist arthroscopy or shoulder arthroscopy. PubMed and Cochrane Library databases
      were searched up to December 2012. Two researchers reviewed each article and
      recorded the condition treated, randomization method, number of randomized
      participants, time of randomization, outcomes measures, blinding, and description
      of dropouts and withdrawals. We used the modified Jadad scale that considers the
      randomization method, blinding, and dropouts/withdrawals; score 0 (lowest
      quality) to 5 (highest quality). The scores for the wrist and shoulder RCTs were
      compared with the Mann-Whitney test. RESULTS: The first references to both wrist
      and shoulder arthroscopy appeared in the late 1970s. The search found 4 wrist
      arthroscopy intervention RCTs (Kienbock's disease, dorsal wrist ganglia, volar
      wrist ganglia, and distal radius fracture; first 3 compared arthroscopic with
      open surgery). The median number of participants was 45. The search found 50
      shoulder arthroscopy intervention RCTs (rotator cuff tears 22, instability 14,
      impingement 9, and other conditions 5). Of these, 31 compared different
      arthroscopic treatments, 12 compared arthroscopic with open treatment, and 7
      compared arthroscopic with nonoperative treatment. The median number of
      participants was 60. The median modified Jadad score for the wrist RCTs was 0.5
      (range 0-1) and for the shoulder RCTs 3.0 (range 0-5) (p = 0.012). CONCLUSION:
      Despite the increasing use of wrist arthroscopy in the treatment of various wrist
      disorders the efficacy of arthroscopically performed wrist interventions has been
      studied in only 4 randomized studies compared to 50 randomized studies of
      significantly higher quality assessing interventions performed through shoulder
      arthroscopy.

PMID- 25059882
TI  - Effective surface coverage of coarse-grained soft matter.
AB  - The surface coverage of coarse-grained macromolecules bound to a solid substrate
      is not simply proportional to the two-dimensional number density because
      macromolecules can overlap. As a function of the overlap probability delta, we
      have developed analytical formulas and computational models capable of
      characterizing this nonlinear relationship. For simplicity, we ignore site-site
      interactions that would be induced by length-scale mismatches between binding
      sites and the radius of gyration of the incident coarse-grained macromolecular
      species. The interactions between macromolecules are modeled with a finite
      bounded potential that allows multiple macromolecules to occupy the same binding
      site. The softness of the bounded potential is thereby reduced to the single
      parameter delta. Through variation of this parameter, completely hard (delta = 0)
      and completely soft (delta = 1) behavior can be bridged. For soft macromolecular
      interactions (delta > 0), multiple occupancy reduces the fraction of sites phi
      occupied on the substrate. We derive the exact transition probability between
      sequential configurations and use this probability to predict phi and the
      distribution of occupied sites. Due to the complexity of the exact phi
      expressions and their analytical intractability at the thermodynamic limit, we
      apply a simplified mean-field (MF) expression for phi. The MF model is found to
      be in excellent agreement with the exact result. Both the exact and MF models are
      applied to an example dynamical system with multibody interactions governed by a
      stochastic bounded potential. Both models show agreement with results measured
      from simulation. 

PMID- 25059883
TI  - Feasibility of perflutren microsphere contrast transthoracic echocardiography in
      the visualization of ventricular endocardium during venovenous extracorporeal
      membrane oxygenation in a validated ovine model.
AB  - BACKGROUND: Transthoracic echocardiography (TTE) during extra corporeal membrane
      oxygenation (ECMO) is important but can be technically challenging. Contrast
      specific TTE can improve imaging in suboptimal studies. These contrast
      microspheres are hydrodynamically labile structures. This study assessed the
      feasibility of contrast echocardiography (CE) during venovenous (VV) ECMO in a
      validated ovine model. METHOD: Twenty-four sheep were commenced on VV ECMO.
      Parasternal long-axis (Plax) and short-axis (Psax) views were obtained pre- and
      postcontrast while on VV ECMO. Endocardial definition scores (EDS) per segment
      were graded: 1 = good, 2 = suboptimal 3 = not seen. Endocardial border definition
      score index (EBDSI) was calculated for each view. Endocardial length (EL) in the
      Plax view for the left ventricle (LV) and right ventricle (RV) was measured.
      RESULTS: Summation EDS data for the LV and RV for unenhanced TTE (UE) versus CE
      TTE imaging: EDS 1 = 289 versus 346, EDS 2 = 38 versus 10, EDS 3 = 33 versus 4,
      respectively. Wilcoxon matched-pairs rank-sign tests showed a significant ranking
      difference (improvement) pre- and postcontrast for the LV (P < 0.0001), RV (P <
      0.0001) and combined ventricular data (P < 0.0001). EBDSI for CE TTE was
      significantly lower than UE TTE for the LV (1.05 +/- 0.17 vs. 1.22 +/- 0.38, P =
      0.0004) and RV (1.06 +/- 0.22 vs. 1.42 +/- 0.47, P = 0.0.0006) respectively.
      Visualized EL was significantly longer in CE versus UE for both the LV (58.6 +/-
      11.0 mm vs. 47.4 +/- 11.7 mm, P < 0.0001) and the RV (52.3 +/- 8.6 mm vs. 36.0 +/
      13.1 mm, P < 0.0001), respectively. CONCLUSIONS: Despite exposure to destructive
      hydrodynamic forces, CE is a feasible technique in an ovine ECMO model. CE
      results in significantly improved EDS and increased EL.

PMID- 25059884
TI  - Improper defibrillator pad usage by emergency medical care providers for
      children: an opportunity for reeducation.
AB  - PURPOSE: Approximately 14 000 pediatric out-of-hospital arrests occur annually.
      With this significant number and the diversity in the training backgrounds of
      medical providers, correct choice and placement of defibrillator pads are
      imperative to ensure maximum efficacy. METHODS: One hundred fifty-two emergency
      medical care providers from 6 medical fields were recruited for the study. Each
      participant answered a series of questions to ascertain baseline knowledge of
      correct defibrillator pad choice and placement in 2 scenarios with mannequins
      weighted less than 15 kg and more than 15kg. After the testing, each participant
      received an educational intervention. Six months after the first phase,
      participants received a questionnaire to ascertain knowledge retention. RESULTS:
      In the primary study phase, for correct pad choice for mannequins weighing less
      than 15 kg and more than 15 kg, overall results were 98% (95% confidence interval
      [CI], 94.1%-100%) and 38.8% (95% CI, 31.4%-46.8%), respectively. In the second
      phase, pad choices for mannequins weighing less than 15 kg and more than 15 kg
      were 77.3% (95% CI, 68.6%-84.2%) and 60% (95% CI, 47.7%-71.1%). The rates of
      correct pad placement during the initial phase for mannequins weighing less than
      15 kg and more than 15 kg were 5.8% (95% CI, 2.8%-11.2%) and 25.7%, respectively
      (95% CI, 19.4%-35.7%). Rates for correct pad placement (<15-kg and >15-kg
      mannequins) improved in the second phase to 68.2% (95% CI, 56%-78.4%) and 71.2%
      (95% CI, 62.8%-81.5%). CONCLUSION: Pediatric emergency providers have poor
      understanding of pad choice and placement. Emergency medical care providers for
      children who are educated about the correct defibrillator pad choices and
      placement have improved knowledge and can retain that knowledge for at least
      6months.

PMID- 25059885
TI  - Long-term efficacy of pressure immobilization bandages in a porcine model of
      coral snake envenomation.
AB  - BACKGROUND: Pressure immobilization bandages delay mortality for 8 hours after
      coral snake envenomation, but long-term efficacy has not been established.
      OBJECTIVE: The objective of this study is to determine the long-term efficacy of
      pressure immobilization bandages after coral snake envenomation in the absence of
      antivenom therapy. METHODS: A randomized, observational pilot study was
      conducted. Ten pigs (17.3-25.6 kg) were sedated, intubated for 5 hours, and
      injected subcutaneously with 10 mg of lyophilized Micrurus fulvius venom
      resuspended in water. Pigs were randomly assigned to a control group (no
      treatment) or a treatment group (compression bandage and splint) approximately 1
      minute after envenomation. Bandage pressure was not controlled. Pigs were
      monitored daily for 21 days for signs of respiratory depression, decreased oxygen
      saturations, and paralysis. In case of respiratory depression, pigs were humanely
      euthanized and time to death recorded. Statistical analysis was performed with
      Fisher exact test, Mann-Whitney U test, and Kaplan-Meier survival curve as
      appropriate. RESULTS: Median survival time of control animals was 307 minutes
      compared with 1172 minutes in treated animals (P = .10). Sixty percent of pigs in
      the treatment group survived to 24 hours vs 0% of control pigs (P = .08). Two of
      the treatment pigs survived to the end point of 21 days but showed necrosis of
      the distal lower extremity. CONCLUSIONS: Long-term survival after coral snake
      envenomation is possible in the absence of antivenom with the use of pressure
      immobilization bandages. The applied pressure of the bandage is critical to
      allowing survival without necrosis. Future studies should be designed to
      accurately monitor the pressures applied.

PMID- 25059886
TI  - Arterial lactate improves the prognostic performance of severity score systems in
      septic patients in the ED.
AB  - OBJECTIVE: To evaluate the prognostic performance of lactate in septic patients
      in the emergency department (ED) and investigate how to add lactate to the
      traditional score systems. METHODS: This was a single-centered, prospective,
      observational cohort study conducted in ED of Beijing Chao-Yang Hospital. The
      study enrolled adult septic patients admitted to the ED. Arterial lactate was
      measured in every patient. Acute Physiology and Chronic Health Evaluation
      (APACHE) II, Sequential Organ Failure Assessment (SOFA), and Mortality in
      Emergency Department Sepsis (MEDS) scores were calculated on ED arrival. The
      primary outcome was 28-day mortality. RESULTS: The average levels of lactate,
      MEDS, APACHE II, and SOFA were much higher in nonsurvivors than in survivors (P <
      .001), and they were the independent predictors of 28-day mortality. Area under
      receiver operating characteristic (AUC) curves of MEDS, APACHE II, SOFA, and
      lactate were 0.74, 0.74, 0.75, and 0.79, respectively. The AUCs of combination
      lactate and MEDS, APACHE II, and SOFA were 0.81, 0.81, and 0.82, respectively and
      were much higher than that of score systems alone (P < .05). The AUCs of modified
      MEDS, APACHE II, and SOFA were 0.80, 0.80, and 0.81, respectively. The prognostic
      value of the modified score systems was superior to the original score systems
      and similar to the combination of the lactate and original score systems.
      CONCLUSIONS: Lactate is a prognostic predictor in septic patients in the ED, and
      it may improve the performance of APACHE II, SOFA, and MEDS scores in predicting
      mortality.

PMID- 25059887
TI  - Hypofractionated radiotherapy for breast cancer acceleration of the START A
      treatment regime: intermediate tolerance and efficacy.
AB  - PURPOSE: Prospective evaluation of accelerated hypofractionated radiotherapy (RT)
      in breast cancer patients treated with 41.6 Gy in 13 fractions plus boost
      delivered five times a week. PATIENTS AND METHODS: Between 03/2009 and 10/2012 98
      consecutive patients aged >55 years presenting with breast cancer (invasive
      cancer: n = 95, ductal carcinoma in situ (DCIS): n = 3) after breast conserving
      surgery were treated in our institution with the following schedule: 41.6 Gy in
      13 fractions 4 times a week and 9 or 12 Gy boost in 3 or 4 fractions (on day 5
      each week), cumulative dose: 50.6 Gy in 3.2 weeks or 53.6 Gy in 3.4 weeks,
      respectively depending on resection status. 56 patients had a T1 tumor, 39 a T2
      tumor. N-status was as follows: N0: n = 71, N1: n = 25, N2/3: n = 2. 23 patients
      (24%) received chemotherapy before RT. A prospectively planned follow-up (FU)
      visit with objective and subjective assessment of treatment tolerance
      (questionnaires) was performed 0 and 8 weeks after RT completion, and one, two
      and four years later, respectively. RESULTS: Mean/median follow-up was 32/28
      months (range: 12-56). After 2 years local control, loco-regional control and
      disease-free survival was 100%, 100%, and 98%, respectively. Overall survival was
      96% at 2 years. Cosmetic outcome was very good with patients being satisfied or
      very satisfied in 99% (n = 86/87), 97% (n = 55/57) and 100% (n = 25/25) after
      one, two and four years after RT, respectively. No grade >= 2 pain was described
      in the 25 patients with a FU of at least 4 years. Fibrosis, telangiectasia and
      edema were found in 7-15%, 0-22% and 0-11% at one, two, and four years,
      respectively, and are comparable to other trials. CONCLUSION: The applied
      hypofractionated RT regime with single doses of 3.2 Gy plus boost doses of 9-12
      Gy in 3-4 fractions applied in 5 sessions a week was effective and well tolerated
      on intermediate term FU.

PMID- 25059888
TI  - Post-traumatic stress symptoms in cancer survivors: relationship to the impact of
      cancer scale and other associated risk factors.
AB  - PURPOSE: The purpose of this study was to determine the prevalence of post
      traumatic stress symptoms in a sample of cancer survivors and to investigate
      their association with the impact of cancer, depressive symptoms, and social
      support. METHODS: We administered a survey to participants in a cancer survivor
      registry. It included: Post-Traumatic Stress Disorder Checklist-Civilian version
      (PCL-C), Impact of Cancer Scale (IOC) v.2, and measures of social support,
      income, and long-term effects of cancer. We performed multivariate analyses to
      estimate associations between PCL-C and other variables. PCL-C score was examined
      as a continuous dependent variable and categorically. RESULTS: Responses were
      available from 162 cancer survivors. Mean age was 51 years (standard deviation
      (SD) 16); mean time since diagnosis was 11 years (SD 10). Mean PCL-C score was 27
      (SD 9, range 17-64); 29% of the sample scored 30 and above, 13% scored 38 and
      above, 7% scored 44 and above. Linear regression indicated that PCL-C scores were
      significantly associated with the IOC negative impact summary scale (NIS) (p <
      0.001), depressive symptoms (p = 0.003), less social support (p = 0.02), and
      lower income (p = 0.03). NIS subscale analyses showed that two subscales, life
      interference (LI) and worry (W), were significantly correlated with PCL-C score
      (LI: p < 0.001; W: p = 0.02). CONCLUSIONS: In this study, the IOC NIS was
      associated with endorsement of PTSD symptoms. Assessing survivors for PTSD
      symptoms with the PCL-C could detect those individuals in need of psychosocial
      support. The IOC may be useful for identifying target areas for interventions to
      reduce these symptoms among cancer survivors.

PMID- 25059890
TI  - Effect of telaprevir on the metabolism and hepatic uptake of tacrolimus (FK506).
AB  - Telaprevir, a chronic hepatitis C virus (HCV) protease inhibitor, is known to be
      a cytochrome P450 (CYP) 3A4/5 substrate and inhibitor. In the present study, the
      in vitro inhibitory effect of telaprevir on the metabolism of tacrolimus in human
      liver microsomes was investigated using 13-O-demethyltacrolimus (M-I) as a
      monitor metabolite. Telaprevir inhibited M-I formation in a time-dependent
      fashion with rate of enzyme inactivation (kinact ) and concentration to reach 50%
      of kinact (KI ) values of 0.113 min(-1) and 0.511 um, respectively. Using the
      inhibition parameters generated, in vitro-in vivo extrapolations were performed
      to evaluate the clinical relevance of the effect of telaprevir on the area under
      the curve versus time (AUC) of tacrolimus. When 750 mg of telaprevir was
      administered orally, the intestinal wall availability (Fg ) of tacrolimus was
      estimated to be increased 3.7- to 7.0-fold. The hepatic intrinsic clearance
      (CLint ) of tacrolimus was also estimated to be decreased 4.4- to 19-fold. These
      results suggest that the increased AUC of tacrolimus in the presence of
      telaprevir was caused by intestinal and hepatic metabolism inhibition. In
      addition, the inhibitory effect of telaprevir on the hepatic uptake of tacrolimus
      was also examined using human cryopreserved hepatocytes. However, no significant
      inhibitory effect was noted, suggesting that the effect of telaprevir on hepatic
      transporters did not contribute to the increase in tacrolimus exposure.

PMID- 25059891
TI  - Second messenger signaling for neuronal polarization: cell mechanics-dependent
      pattern formation.
AB  - Neuronal polarization is a critical step in the neuronal morphogenesis. Despite
      the identification of several evolutionarily conserved factors for neural
      polarization, the exact mechanisms by which cells initiate and maintain polarity
      remain to be characterized. Here, we review the recent progress on the roles of
      second messengers, specifically the cyclic nucleotides and membrane-associated
      phospholipids, in the initiation, propagation, and integration of polarization
      signals, and propose an inhibitor-free model for neural polarization. The
      characteristic features of neuron polarization include the formation of single
      axon and multiple dendrites. These features involve chemical and mechanical
      mechanisms such as reaction-diffusion and tug-of-war, by which second messengers
      can act in concert to initiate and stabilize the cellular asymmetry.
      Nevertheless, biochemical factors eliciting the long-range inhibition remain
      ambiguous. Thus, we provide a simple, inhibitor-free model that can incorporate
      known cytochemical and cytomechanical factors, and produce features of neuronal
      polarization in environments provided with minimized extracellular regulators.

PMID- 25059889
TI  - Lagrangian postprocessing of computational hemodynamics.
AB  - Recent advances in imaging, modeling, and computing have rapidly expanded our
      capabilities to model hemodynamics in the large vessels (heart, arteries, and
      veins). This data encodes a wealth of information that is often under-utilized.
      Modeling (and measuring) blood flow in the large vessels typically amounts to
      solving for the time-varying velocity field in a region of interest. Flow in the
      heart and larger arteries is often complex, and velocity field data provides a
      starting point for investigating the hemodynamics. This data can be used to
      perform Lagrangian particle tracking, and other Lagrangian-based postprocessing.
      As described herein, Lagrangian methods are necessary to understand inherently
      transient hemodynamic conditions from the fluid mechanics perspective, and to
      properly understand the biomechanical factors that lead to acute and gradual
      changes of vascular function and health. The goal of the present paper is to
      review Lagrangian methods that have been used in post-processing velocity data of
      cardiovascular flows. 

PMID- 25059892
TI  - Effects of pool isolation on trophic ecology of fishes in a highland stream.
AB  - The objective of this study was to examine the effects of pool isolation on fish
      diet and to answer three questions: Were food resources different or reduced in
      isolated compared with connected pools? Were fishes more selective and did they
      increase resource partitioning in isolated pools? Would individuals exhibit
      increased gastrointestinal tract (GIT) length in isolation to aid nutrient
      absorption? Benthic macroinvertebrate density and richness were significantly
      lower in isolated pools compared with connected pools; fishes became more
      selective and partitioned resources more in isolated pools and all three species
      showed an increase in GIT length in isolated pools compared with connected pools.
      With a changing climate predicted to increase intermittency within headwater
      streams, the results show that these fishes have the adaptive ability to respond
      and continue to survive. 

PMID- 25059893
TI  - Live attenuated influenza vaccine.
AB  - Cold-adapted Ann Arbor based live attenuated influenza vaccine (LAIV) has been
      available in the USA since 2003. The vaccine is efficacious against influenza
      infection. Features of LAIV include: easy administration suitable for mass
      immunization, cross-reactivity to drifted strains for broader coverage, and
      establishment of herd immunity for control of influenza spread. Annual seasonal
      LAIV now contains four strains against influenza A H1N1, H3N2, influenza B
      Victoria, and B-Yamagata lineages that are co-circulating in humans. LAIV played
      a significant role in protecting the public from the 2009 H1N1 pandemic and has
      been evaluated for pandemic preparedness. Pandemic vaccines including influenza
      H2, H5, H6, H7, and H9 subtypes have been produced and evaluated in preclinical
      and small-scale phase I clinical studies. This review summarizes the current
      status and perspectives of seasonal and pandemic LAIV. 

PMID- 25059894
TI  - Development of dynamic models of the Mauch prosthetic knee for prospective gait
      simulation.
AB  - Recent advances in computational modeling and simulation of human movement makes
      it possible to isolate and predict the potential contributions of a prosthetic
      device to the overall system performance. The Mauch S-N-S knee is one of the most
      widely used prosthetic knees in the market. The goal of this study is to develop
      dynamic models of the Mauch S-N-S knee for predictive simulation of a
      transfemoral amputee's gait under idealized conditions. Based on the functional
      description of the Mauch S-N-S prosthetic knee from the literature, a combined
      bench test and data fitting approach employing modified slow, normal, and fast
      gait patterns and nine combinations of stance and swing damping settings were
      performed. Two types of dynamic models, 2-phase and 4-phase models, of the Mauch
      S-N-S prosthetic knee were developed. The range of the coefficient of
      determination of the two dynamic models, when compared to the test data, was from
      39.9 to 95%. Both dynamic models of this study can be utilized in musculoskeletal
      modeling studies, to better understand amputee gait and the contributions and
      interactions of various prosthetic leg components to the ambulatory performance.

PMID- 25059895
TI  - Comparison of discrete-point vs. dimensionality-reduction techniques for
      describing performance-related aspects of maximal vertical jumping.
AB  - The aim of this study was to assess and compare the ability of discrete point
      analysis (DPA), functional principal component analysis (fPCA) and analysis of
      characterizing phases (ACP) to describe a dependent variable (jump height) using
      vertical ground reaction force curves captured during the propulsion phase of a
      countermovement jump. FPCA and ACP are continuous data analysis techniques that
      reduce the dimensionality of a data set by identifying phases of variation (key
      phases), which are used to generate subject scores that describe a subject's
      behavior. A stepwise multiple regression analysis was used to measure the ability
      to describe jump height of each data analysis technique. Findings indicated that
      the order of effectiveness (high to low) across the examined techniques was: ACP
      (99%), fPCA (78%) and DPA (21%). DPA was outperformed by fPCA and ACP because it
      can inadvertently compare unrelated features, does not analyze the whole data set
      and cannot examine important features that occur solely as a phase. ACP
      outperformed fPCA because it utilizes information within the combined magnitude
      time domain, and identifies and examines key phases separately without the
      deleterious interaction of other key phases.

PMID- 25059896
TI  - Is post-contrast MRI a valuable method for the study of the nutrition of the
      intervertebral disc?
AB  - Decreased nutrition has been proposed as a potential mechanism leading to
      intervertebral disc degeneration. A method to investigate it in vivo is the MRI
      evaluation of the transport of a paramagnetic contrast agent, which is assumed to
      diffuse through the endplate to the disc using the same mechanisms as the cell
      nutrients. However, previous numerical studies questioned the value of this
      method as a model to investigate disc nutrition. To assess its validity, a
      parametric osmoporoelastic finite element model of a lumbar intervertebral disc
      incorporating diffusion and convection of a solute (representing the contrast
      agent) was developed. A Taguchi sensitivity analysis was performed in order to
      assess the relevance of various parameters which influence the solute transport.
      Subsequently, a full-factorial sensitivity analysis was used to investigate
      specifically the diffusion coefficients of the contrast agent. The most important
      parameters in determining the results were the disc height, the diffusion
      coefficients and the pharmacokinetic of the contrast agent. However, diffusion
      coefficients values as measured in in vitro studies would lead to insubstantial
      enhancement of the MRI signal. Thus, transport mechanisms other than pure
      diffusion should be active in in vivo transport of the contrast agent. In
      conclusion, the study showed that post-contrast MRI may not be suited for a
      quantitative analysis, but only for a qualitative examination aimed for example
      to detect endplate lesions. Open questions remain on the use of post-contrast MRI
      for the investigation of the relevance of reduced nutrition as a trigger to disc
      degeneration. 

PMID- 25059897
TI  - Lessons learned through leadership.

PMID- 25059898
TI  - Is an appropriate wheelchair becoming out of reach?

PMID- 25059899
TI  - The value of maintaining primary board certification in physical medicine and
      rehabilitation.

PMID- 25059900
TI  - Ultrasonography of a sciatic nerve injury caused by a gunshot wound.

PMID- 25059901
TI  - Experiencing death: an insider's perspective.
AB  - For millennia, human beings have wondered what happens after death. What is the
      first-person experience of dying and being brought back to life? Technological
      advances in resuscitation science have now added an intriguing new chapter to the
      literature of out-of-body or near-death experiences by eliciting detailed and
      vivid accounts of those who have approached the threshold of death. Steve
      Paulson, executive producer and host of To the Best of Our Knowledge, moderated a
      discussion that included neurologist Kevin Nelson, neuropsychiatrist Peter
      Fenwick, emergency medicine expert Sam Parnia, and orthopedic surgeon and
      drowning survivor Mary Neal; they share some remarkable stories and discuss how
      they analyze such experiences in light of their own backgrounds and training. The
      following is an edited transcript of the discussion from December 11, 2013, 7:00
      8:30 PM, at the New York Academy of Sciences in New York City. 

PMID- 25059902
TI  - 'Not that I want to be thought of as a hero': narrative analysis of performative
      masculinities and the experience of informal cancer caring.
AB  - Providing care to a partner with cancer can have a significant impact on a
      carer's well-being and experience of subjectivity. However, there is little
      research examining how men experience the role of cancer carer, and in
      particular, how they negotiate constructions of gender in this role. This paper
      draws on a single case study of a heterosexual man caring for his partner, and
      conducts a narrative analysis of the construction and performance of masculine
      subjectivity. It was found that rather than inhabiting a stable masculinity, this
      carer engaged in a complex negotiation of masculinities, enacting a caring role
      associated with victimisation, rejection, distress and powerlessness, as well as
      strength and heroic resilience. We highlight the importance of the relationship
      context to the experience of caring, and suggest that research into the gendered
      experience of cancer care needs to acknowledge the active negotiation of
      masculinities and caring. We also discuss the utility of case study research in
      analyses of masculinity and cancer care, and in health psychology more broadly. 

PMID- 25059903
TI  - Incidence of cardioembolic stroke including paradoxical brain embolism in
      patients with acute ischemic stroke before and after the Great East Japan
      Earthquake.
AB  - BACKGROUND: The incidence of heart disease or deep vein thrombosis (DVT)
      reportedly increased after the Great East Japan Earthquake. We hypothesized that
      the incidence of cardioembolic stroke (CES) including paradoxical brain embolism
      (PBE) among patients with acute stroke would increase after the earthquake due to
      cessation of antithrombotic therapy or the increase in heart disease and DVT
      associated with the evacuation. The aim of this study is to evaluate the changes
      in the prevalence of DVT and the incidence of CES including PBE in acute ischemic
      stroke before and after the earthquake. METHODS: We retrospectively studied 1,044
      consecutive ischemic stroke patients (73.1 +/- 12.5 years old, male 61.5%) who
      were admitted to a comprehensive stroke center (from January 2010 through March
      2012) located in the earthquake disaster area within 7 days after stroke onset.
      The prevalence of DVT and the incidence of CES including PBE were compared before
      and after the earthquake of 11 March 2011. RESULTS: The median of the initial
      National Institutes of Health Stroke Scale (NIHSS) scores was 4 (interquartile
      range: 1-8). Two hundred and eighty-two patients (27.0% of those surveyed) were
      diagnosed with CES. After adjustment for sex, age, NIHSS score, and patient's
      residential address, the proportion of CES patients was significantly increased
      after the earthquake (odds ratio, OR 1.61, 95% confidence interval, 95% CI: 1.20
      2.17). Eighty-nine patients (8.5% of those surveyed) had DVT. Compared with 2010
      findings, the prevalence of DVT was significantly increased in the fourth quarter
      of 2011 and the first quarter of 2012 (OR 1.85, 95% CI: 1.05-3.24). Nineteen
      (1.8% of those surveyed) were diagnosed with PBE. The proportion of PBE patients
      was also significantly increased in the second half of 2011 (OR 3.69, 95% CI:
      1.28-12.1). CONCLUSIONS: The incidence of CES was significantly increased after
      the earthquake, compared with the period before the earthquake. We encountered
      more PBE in the period from 3 to 9 months after the earthquake and found more DVT
      in the acute ischemic stroke patients in the period from 6 through 12 months
      after the earthquake. In these types of disasters, we have to ensure the
      distribution of drugs, including antithrombotics, and support the prevention of
      DVT in the refugees.

PMID- 25059904
TI  - Effect of cryoprotectant and equilibration temperature on cryopreservation of
      Lama glama spermatozoa.
AB  - The aim of this study was to determine the effect of two equilibration
      temperatures (5  degrees C and room temperature) and two cryoprotectants
      (glycerol and dimethylformamide, both at 7%) on llama sperm cryopreservation.
      Llama ejaculates were divided into four aliquots. A lactose-EDTA-egg yolk (LEEY)
      extender with either 7% glycerol (LEEY-G) or 7% dimethylformamide (LEEY-DMF) was
      added to two of the aliquots, which were equilibrated for 20 min at room
      temperature and subsequently frozen. The other two aliquots were extended in
      LEEY, cooled to 5  degrees C, then LEEY-G or LEEY-DMF was added, equilibrated for
      20 min at 5  degrees C and frozen. No significant differences (P > 0.05) were
      observed in membrane function and chromatin condensation between any of the
      freeze-thawing protocols. Post-thaw motility was greater (P < 0.05) in LEEY-DMF
      than LEEY-G. DNA fragmentation was not different between raw and frozen semen
      with LEEY-DMF but was high in all samples with glycerol. Our results indicate
      that 7% glycerol would be detrimental for llama spermatozoa, but further studies
      are needed to evaluate effectiveness if used at lower concentrations.
      Dimethylformamide preserved motility and DNA integrity of frozen-thawed llama
      spermatozoa and could be used to replace glycerol at the concentrations used in
      this study.

PMID- 25059905
TI  - The differential expression of alternatively spliced transcripts and imprinting
      status of MEG9 gene in cows.
AB  - Meg9/Mirg (maternally expressed gene 9/microRNA containing gene), a non-coding
      RNA (ncRNA) comprising many alternatively splicing isoforms, has been identified
      as maternally expressed in mouse and sheep, but its imprinting status and
      splicing variants are still unknown in cattle. In this study, we found three
      splicing variants of the cattle MEG9 gene expressed in a tissue-specific manner.
      A single nucleotide polymorphism site (SNP c.1354C>G) was identified in exon 3 of
      cattle MEG9 and used to distinguish between monoallelic and biallelic expression.
      Our results showed that MEG9 exhibited monoallelic expression in all examined
      cattle tissues by comparing sequencing results between genomic DNA and cDNA
      levels at the c.1354C>G SNP site, suggesting that MEG9 is imprinted in cattle. 

PMID- 25059906
TI  - Quantum rules for planar boron nanoclusters.
AB  - This article presents the use of free particle models to obtain quantum rules for
      planar boron clusters, with nuclearities in the range from seven to twenty. The
      information obtained from the models is being compared with electronic structure
      calculations based on the DFT method. Separate rules for in-plane and out-of
      plane bonding are derived. In-plane bonding is precise on the cluster boundary
      and forms a network of alternating triangular 3c-2e bonds on the inside. The out
      of-plane bonding is strongly delocalized and only depends on the global shape and
      size of the cluster. 

PMID- 25059907
TI  - Lamins of the sea lamprey (Petromyzon marinus) and the evolution of the
      vertebrate lamin protein family.
AB  - Lamin proteins are found in all metazoans. Most non-vertebrate genomes including
      those of the closest relatives of vertebrates, the cephalochordates and
      tunicates, encode only a single lamin. In teleosts and tetrapods the number of
      lamin genes has quadrupled. They can be divided into four sub-types, lmnb1,
      lmnb2, LIII, and lmna, each characterized by particular features and functional
      differentiations. Little is known when during vertebrate evolution these features
      have emerged. Lampreys belong to the Agnatha, the sister group of the
      Gnathostomata. They split off first within the vertebrate lineage. Analysis of
      the sea lamprey (Petromyzon marinus) lamin complement presented here, identified
      three functional lamin genes, one encoding a lamin LIII, indicating that the
      characteristic gene structure of this subtype had been established prior to the
      agnathan/gnathostome split. Two other genes encode lamins for which orthology to
      gnathostome lamins cannot be designated. Search for lamin gene sequences in all
      vertebrate taxa for which sufficient sequence data are available reveals the
      evolutionary time frame in which specific features of the vertebrate lamins were
      established. Structural features characteristic for A-type lamins are not found
      in the lamprey genome. In contrast, lmna genes are present in all gnathostome
      lineages suggesting that this gene evolved with the emergence of the
      gnathostomes. The analysis of lamin gene neighborhoods reveals noticeable
      similarities between the different vertebrate lamin genes supporting the
      hypothesis that they emerged due to two rounds of whole genome duplication and
      makes clear that an orthologous relationship between a particular vertebrate
      paralog and lamins outside the vertebrate lineage cannot be established. 

PMID- 25059908
TI  - Playing beautifully when you have to be fast: spatial and temporal symmetries of
      movement patterns in skilled piano performance at different tempi.
AB  - Humans are capable of learning a variety of motor skills such as playing the
      piano. Performance of these skills is subject to multiple constraints, such as
      musical phrasing or speed requirements, and these constraints vary from one
      context to another. In order to understand how the brain controls highly skilled
      movements, we investigated pianists playing musical scales with their left or
      right hand at various speeds. Pianists showed systematic temporal deviations away
      from regularity. At slow tempi, pianists slowed down at the beginning and end of
      the movement (which we call phrasal template). At fast tempi, temporal deviation
      traces consisted of three peak delays caused by a thumb-under manoeuvre (which we
      call neuromuscular template). Intermediate tempi were a linear combination trade
      off between these two. We introduce and cross-validate a simple four-parameter
      model that predicted the timing deviation of each individual note across tempi
      (R(2) = 0.70). The model can be fitted on the data of individual pianists,
      providing a novel quantification of expert performance. The present study shows
      that the motor system can generate complex movements through a dynamic
      combination of simple movement templates. This provides insight into how the
      motor system flexibly adapts to varying contextual constraints.

PMID- 25059909
TI  - Jaw-opening accuracy is not affected by masseter muscle vibration in healthy men.
AB  - There is a functional integration between the jaw and neck regions with head
      extension-flexion movements during jaw-opening/closing tasks. We recently
      reported that trigeminal nociceptive input by injection of hypertonic saline into
      the masseter muscle altered this integrated jaw-neck function during jaw
      opening/closing tasks. Thus, in jaw-opening to a predefined position, the head
      neck component increased during pain. Previous studies have indicated that muscle
      spindle stimulation by vibration of the masseter muscle may influence jaw
      movement amplitudes, but the possible effect on the integrated jaw-neck function
      is unknown. The aim of this study was to investigate the effect of masseter
      muscle vibration on jaw-head movements during a continuous jaw-opening/closing
      task to a target position. Sixteen healthy men performed two trials without
      vibration (Control) and two trials with bilateral masseter muscle vibration
      (Vibration). Movements of the mandible and the head were registered with a
      wireless three-dimensional optoelectronic recording system. Differences in jaw
      opening and head movement amplitudes between Control and Vibration, as well as
      achievement of the predefined jaw-opening target position, were analysed with
      Wilcoxon's matched pairs test. No significant group effects from vibration were
      found for jaw or head movement amplitudes, or in the achievement of the target
      jaw-opening position. A covariation between the jaw and head movement amplitudes
      was observed. The results imply a high stability for the jaw motor system in a
      target jaw-opening task and that this task was achieved with the head-neck and
      jaw working as an integrated system. 

PMID- 25059910
TI  - A cognitive dual task affects gait variability in patients suffering from chronic
      low back pain.
AB  - Chronic pain and gait variability in a dual-task situation are both associated
      with higher risk of falling. Executive functions regulate (dual-task) gait
      variability. A possible cause explaining why chronic pain increases risk of
      falling in an everyday dual-task situation might be that pain interferes with
      executive functions and results in a diminished dual-task capability with
      performance decrements on the secondary task. The main goal of this experiment
      was to evaluate the specific effects of a cognitive dual task on gait variability
      in chronic low back pain (CLBP) patients. Twelve healthy participants and twelve
      patients suffering from CLBP were included. The subjects were asked to perform a
      cognitive single task, a walking single task and a motor-cognitive dual task.
      Stride variability of trunk movements was calculated. A two-way ANOVA was
      performed to compare single-task walking with dual-task walking and the single
      cognitive task performance with the motor-cognitive dual-task performance. We did
      not find any differences in both of the single-task performances between groups.
      However, regarding single-task walking and dual-task walking, we observed an
      interaction effect indicating that low back pain patients show significantly
      higher gait variability in the dual-task condition as compared to controls. Our
      data suggest that chronic pain reduces motor-cognitive dual-task performance
      capability. We postulate that the detrimental effects are caused by central
      mechanisms where pain interferes with executive functions which, in turn, might
      contribute to increased risk of falling. 

PMID- 25059911
TI  - Pain reported during prolonged standing is associated with reduced anticipatory
      postural adjustments of the deep abdominals.
AB  - Within the context of low back pain, the measurement of deep abdominal
      anticipatory postural adjustments (APAs) during rapid limb movement has received
      much interest. There is dispute about the association between APAs and back pain.
      Moreover, there is limited evidence examining compensatory postural adjustments
      (CPAs) in back pain. This study examined the relationship between APAs and CPAs
      with pain reported in the low back during 2 h of prolonged standing. Twenty-six
      participants with no history of severe back pain performed 2-h prolonged
      standing. APAs and CPAs of the deep abdominal muscles (transverse
      abdominis/internal obliques) were measured by surface electromyography during
      rapid shoulder flexion and extension. APAs and CPAs measured pre-standing
      revealed symmetrical anticipatory activity, but an asymmetry between the
      different sides of the abdominal wall for CPAs. APAs and CPAs measured pre
      standing were not associated with pain reported during standing. For the whole
      group, APA amplitudes were reduced post-standing during shoulder flexion (p =
      0.005). Pain reported during standing was associated with the changes in APA
      amplitudes post-standing (rs = 0.43, p = 0.002). These findings support previous
      research using hypertonic saline injections to induce back pain that showed
      reduced APA amplitudes, and extends findings to suggest pain does not effect
      compensatory postural adjustments.

PMID- 25059912
TI  - A leader-follower relationship in joint action on a discrete force production
      task.
AB  - The present study examined the development of a leader-follower relationship in
      joint action performed by participants with different skill levels. Two
      participants were instructed to produce discrete isometric forces such that the
      sum of the forces was the target force. The task did not prescribe the onset time
      or share of force each participant contributed to the target force. Although
      novices with low force variability did not produce an earlier force than those
      with high force variability in the novice-novice group, experienced participants
      produced an earlier force than novices in the novice-experienced group. While
      participants with low force variability always produced a stronger force than
      those with high force variability in both the groups, there was no significant
      difference in force distributions between participants with low and high force
      variabilities. Although a novice-experienced pair produced force more
      complementarily than a novice-novice pair in the first practice block, the
      difference between pairs vanished after the first practice block, suggesting that
      leader-follower relations were not always beneficial to task performance. In
      addition, practice of the joint action did not transfer to individual action. 

PMID- 25059913
TI  - Integrated approach for studying adaptation mechanisms in the human somatosensory
      cortical network.
AB  - Magnetoencephalography and independent component analysis (ICA) was utilized to
      study and characterize neural adaptation in the somatosensory cortical network.
      Repetitive punctate tactile stimuli were applied unilaterally to the dominant
      hand and face using a custom-built pneumatic stimulator called the TAC-Cell. ICA
      based source estimation from the evoked neuromagnetic responses indicated
      cortical activity in the contralateral primary somatosensory cortex (SI) for face
      stimulation, while hand stimulation resulted in robust contralateral SI and
      posterior parietal cortex (PPC) activation. Activity was also observed in the
      secondary somatosensory cortical area (SII) with reduced amplitude and higher
      variability across subjects. There was a significant difference in adaptation
      rate between SI and higher-order somatosensory cortices for hand stimulation.
      Adaptation was significantly dependent on stimulus frequency and pulse index
      within the stimulus train for both hand and face stimulation. The peak latency of
      the activity was significantly dependent on stimulation site (hand vs. face) and
      cortical area (SI vs. PPC). The difference in the peak latency of activity in SI
      and PPC is presumed to reflect a hierarchical serial-processing mechanism in the
      somatosensory cortex. 

PMID- 25059914
TI  - Tracing the time course of n - 2 repetition costs in task switching.
AB  - In order to flexibly adapt to a permanently changing environment, it is necessary
      to inhibit previously activated but now irrelevant processing pathways.
      Empirically, this inhibition manifests itself only indirectly in terms of a cost
      of reengaging a previously inhibited pathway (n - 2 repetition costs). While
      imaging studies suggest an involvement of the prefrontal cortex in this type of
      inhibition, it has recently been argued that the underlying processes are
      implicated not in triggering inhibition, but in overcoming it. To disentangle
      these processes on a behavioral level, we investigated the time course of
      inhibition using a cued task switching paradigm. The response-cue interval
      (between the response of trial n - 1 and the cue of trial n) was varied in five
      steps to capture its influence on inhibition in a fine-grained manner. The
      results suggest that the impact of inhibitory processes increases during the
      first 200-300 ms after the response of the previous trial, reaches its full
      extent with about 300 ms, and starts to diminish after that. Therefore, future
      research on the neural correlates of n - 2 repetition costs should employ
      techniques with a high temporal resolution that are able to capture this presumed
      time course of inhibitory processes.

PMID- 25059915
TI  - Diet and diet-related disorders in captive ruminants at the national zoological
      gardens of South Africa.
AB  - Although diet-related disorders have received much attention in the zoo
      literature, evidence-based results on relationships between diet and disease are
      still rare, often due to a lack of quantitative dietary information that can be
      linked to clinical or necropsy reports. We investigated 24 species of captive
      ruminants from one facility for which quantitative feeding instructions and
      necropsy reports between 1991 and 2012 were available. Species were classified as
      grazer (GR), intermediate feeder (IM), or browser (BR). Feeding type and body
      mass were significantly correlated to the diet fed, with smaller and BR species
      receiving higher proportions of non-roughage diet items. There were no
      significant differences between feeding types in the occurrence of
      parakeratosis/ruminitis/acidosis (PRA) at necropsy, but in body condition score,
      with BR more often in poor and less often in excellent body condition at
      necropsy. While there was no direct correlation between the proportion of non
      roughage diet items and PRA across species, there was a significant effect of the
      proportion of non-roughage diet items on PRA when body mass was also taken into
      account: larger species, and those that received more non-roughage diet items,
      had higher prevalence of PRA. The results underline that diet and lack of
      structured feed items can be associated with the disease complex of acidosis in
      ruminants, but also suggest that this is modified by factors related to animal
      size. These latter may include susceptibility to acidosis, or husbandry-related
      opportunities to monopolize non-roughage feeds and ingest higher proportions than
      intended by feeding instructions.

PMID- 25059916
TI  - Founder mutation in dystonin-e underlying autosomal recessive epidermolysis
      bullosa simplex in Kuwait.
AB  - Only two homozygous nonsense mutations in the epidermal isoform of the dystonin
      gene, DST-e, have been reported previously in autosomal recessive epidermolysis
      bullosa simplex (EBS); the affected pedigrees were Kuwaiti and Iranian. This
      subtype of EBS is therefore considered to be a rare clinicopathological entity.
      In this study, we identified four seemingly unrelated Kuwaiti families in which a
      total of seven individuals had predominantly acral trauma-induced blistering
      since infancy. All affected individuals were homozygous for the mutation
      p.Gln1124* in DST-e, the same mutation that was identified in the originally
      reported family from Kuwait. Haplotype analysis in the five pedigrees (including
      the previous case) revealed a shared block of ~60 kb of genomic DNA across the
      site of the mutation, consistent with a founder effect. Most heterozygotes had no
      clinical abnormalities although one subject had mild transient skin fragility
      during childhood, an observation noted in the previously reported Iranian
      pedigree, suggesting that the condition may also be semidominant in some
      pedigrees rather than purely autosomal recessive. Our study reveals propagation
      of a mutant ancestral allele in DST-e throughout Kuwait, indicating that this
      subtype of EBS may be more common in Kuwait, and perhaps other Middle Eastern
      countries, than is currently appreciated. 

PMID- 25059918
TI  - The use of ultrasound-guided regional anaesthetic techniques in neonates and
      young infants.
AB  - Optimal pain therapy during the perioperative period or at the neonatal intensive
      care unit and subsequent reduced use of opioids and various sedative drugs is an
      important factor for patients care. The use of various regional anaesthetic
      techniques in experienced hands provides excellent pain relief and has the
      potency to reduce the requirement for perioperative mechanical ventilation. Most
      of regional anaesthesia techniques are applicable also in neonates and young
      infants and can be used in an effective and safe manner. Ultrasound guidance
      should be used for all regional anaesthetic techniques to increase efficacy and
      safety. The spectrum of indications for ultrasound-guided regional anaesthesia in
      babies and infants are surgery, selective pain therapy and sympathicolysis. This
      review reflects an expert-based description of the most recent developments in
      ultrasound-guided regional anaesthetic techniques in babies and infants. 

PMID- 25059917
TI  - Identification of the valence and coordination environment of the particulate
      methane monooxygenase copper centers by advanced EPR characterization.
AB  - Particulate methane monooxygenase (pMMO) catalyzes the oxidation of methane to
      methanol in methanotrophic bacteria. As a copper-containing enzyme, pMMO has been
      investigated extensively by electron paramagnetic resonance (EPR) spectroscopy,
      but the presence of multiple copper centers has precluded correlation of EPR
      signals with the crystallographically identified monocopper and dicopper centers.
      A soluble recombinant fragment of the pmoB subunit of pMMO, spmoB, like pMMO
      itself, contains two distinct copper centers and exhibits methane oxidation
      activity. The spmoB protein, spmoB variants designed to disrupt one or the other
      or both copper centers, as well as native pMMO have been investigated by EPR,
      ENDOR, and ESEEM spectroscopies in combination with metal content analysis. The
      data are remarkably similar for spmoB and pMMO, validating the use of spmoB as a
      model system. The results indicate that one EPR-active Cu(II) ion is present per
      pMMO and that it is associated with the active-site dicopper center in the form
      of a valence localized Cu(I)Cu(II) pair; the Cu(II), however, is scrambled
      between the two locations within the dicopper site. The monocopper site observed
      in the crystal structures of pMMO can be assigned as Cu(I). (14)N ENDOR and ESEEM
      data are most consistent with one of these dicopper-site signals involving
      coordination of the Cu(II) ion by residues His137 and His139, the other with
      Cu(II) coordinated by His33 and the N-terminal amino group. (1)H ENDOR
      measurements indicate there is no aqua (HxO) ligand bound to the Cu(II), either
      terminally or as a bridge to Cu(I). 

PMID- 25059919
TI  - Declarative titles in original research papers in dermatologic journals 1974
      2014.

PMID- 25059920
TI  - A new spectrofluorimetric method for the determination of some tetracyclines
      based on their interfering effect on resonance fluorescence energy transfer.
AB  - A rapid, simple, inexpensive and highly sensitive spectrofluorimetric method was
      developed for the determination of trace amounts of some tetracyclines (TCs),
      namely tetracycline hydrochloride (TCH), oxytetracycline hydrochloride (OTCH) and
      minocycline hydrochloride (MCH). Binding rhodamine B (RhB) to gold nanoparticles
      (Au NPs) resulted in quenching of the fluorescence of RhB by a resonance energy
      transfer (FRET) mechanism, with Au NPs as the energy acceptors. The presence of
      TCs caused the release of RhB molecules and recovered their fluorescence, and
      this was used as a basis for the quantitative determination of TCs. The reaction
      was monitored spectrofluorimetrically by measuring the increase in fluorescence
      of RhB at 572 nm starting 5 min after mixing the reagents in Tris buffer solution
      (pH 6.5). The effect of various experimental factors such as buffer type, pH,
      concentrations of the involved reagents and reaction time were studied to
      optimize the reaction conditions. Under optimum conditions, the calibration
      graphs were linear within the ranges 2.08 * 10(-9) -1.04 * 10(-6)  mol/L, 2.01 *
      10(-9) -1.00 * 10(-6)  mol/L and 2.02 * 10(-9) -1.01 * 10(-6)  mol/L and
      detection limits (LODs) of 0.61 * 10(-9) , 0.32 * 10(-9) and 0.66 * 10(-9)  mol/L
      were calculated for TCH, OTCH and MCH, respectively, with corresponding percent
      relative standard deviations (%RSDs) of 1.18, 1.21 and 1.54 (n = 5). The method
      was successfully applied to the determination of TCs in drinking water, human
      urine, bovine milk and breast milk samples.

PMID- 25059921
TI  - Association between nutritional screening via the Controlling Nutritional Status
      index and bone mineral density in chronic liver disease of various etiologies.
AB  - AIM: Bone density disorders are prevalent in patients with chronic liver disease
      (CLD), who commonly present with hepatic osteodystrophy. However, the
      relationship between nutritional status and bone mineral density (BMD) has been
      scarcely studied in CLD. METHODS: This single-center, cross-sectional study
      included outpatients consecutively diagnosed with CLD during a 1.5-year period.
      The nutritional status was assessed with the Controlling Nutritional Status
      (CONUT) index; dual-energy X-ray absorptiometry scans and parameters of bone
      mineral metabolism were carried out. Bone fracture risk was estimated with the
      World Health Organization FRAX tool. RESULTS: Among the 126 patients recruited
      (58.7% male), osteopenia and osteoporosis were present in 31.1% and 10.7%,
      respectively. The 10-year fracture risk was significantly higher among women.
      Malnutrition estimated with the CONUT index was present in 29.9% of patients and
      was significantly more frequent in cirrhotic patients, 63.4% of whom were
      malnourished. Malnutrition stage directly correlated with hepatic function as
      expressed by the Model for End-Stage Liver Disease index. A non-significant
      relationship between CONUT-assessed nutritional status and BMD was documented. 25
      Hydroxyvitamin-D3 (25[OH]-D3) and fracture risk correlated positively with the
      CONUT stage, and total cholesterol had an inverse relationship with BMD.
      CONCLUSION: Malnutrition assessed by the CONUT was very frequent in patients with
      liver cirrhosis. The CONUT score inversely correlated with liver function, while
      malnutrition stage directly correlated with BMD, fracture risk and 25(OH)-D3.
      Total cholesterol showed a negative association with BMD in this population.

PMID- 25059923
TI  - Retraction statement: 'Species distributions shift downward across western North
      America' by M.A. Harsch and J. Hille Ris Lambers.
AB  - The above article, published online on 18 August 2014 in Wiley Online Library
      (wileyonlinelibrary.com), has been retracted by agreement between the authors, Dr
      Melanie Harsch and Associate Professor Janneke Hille Ris Lambers, journal Editor
      in-Chief, Professor Stephen Long, and John Wiley & Sons Ltd. The retraction has
      been agreed for the following reasons: a coding error affected the results and
      therefore invalidated the broadscale conclusions presented in the article. The
      article presented broad-scale patterns of species distribution shifts in response
      to recent climate change. Unfortunately, it has since been found that one
      approach used to account for sampling bias, the null model approach, was affected
      by the coding error. Following the identification of the coding error, we are
      therefore retracting the article. We thank Drs Adam Wolf and William Anderegg for
      bringing this issue to our attention.

PMID- 25059922
TI  - Hormone and radiotherapy versus hormone or radiotherapy alone for non-metastatic
      prostate cancer: a systematic review with meta-analyses.
AB  - AIMS: Radiotherapy is standard treatment for localised prostate cancer and is
      often combined with hormone treatment to prevent androgen stimulation of prostate
      cancer. Hormone therapy carries significant morbidity and can only be justified
      in the radical treatment of localised disease if it can be balanced against a
      significant gain in disease control and survival. MATERIALS AND METHODS: We
      searched Medline, Premedline, Embase, Cochrane Library, Web of Science (SCI &
      SSCI) and Biomed Central for randomised controlled trials published in English
      comparing radiotherapy or hormone therapy alone with radiotherapy and hormone
      therapy in combination as first-line treatment in patients with non-metastatic
      prostate cancer reporting overall survival, disease-free survival, distant
      metastases-free survival, biochemical survival, adverse events (including
      cardiovascular) and/or health-related quality of life. RESULTS: Fourteen trials
      were included and showed that combination therapy was associated with better or
      similar survival and disease-free outcomes compared with single-modality
      treatment, and that this may particularly be the case for patients with higher
      risk disease. The results also suggested that combination therapy is associated
      with more and worse adverse events and quality of life, although this was not
      always the case. Some of the results are at risk of reporting bias. CONCLUSION:
      The published data support the use of combined treatment with androgen
      deprivation and radiotherapy for intermediate- and high-risk localised and
      locally advanced prostate cancer. Optimal timing, duration, formulation and the
      management of side-effects remain important questions for further research.

PMID- 25059924
TI  - P2X receptors regulate adenosine diphosphate release from hepatic cells.
AB  - Extracellular nucleotides act as paracrine regulators of cellular signaling and
      metabolic pathways. Adenosine polyphosphate (adenosine triphosphate (ATP) and
      adenosine diphosphate (ADP)) release and metabolism by human hepatic carcinoma
      cells was therefore evaluated. Hepatic cells maintain static nanomolar
      concentrations of extracellular ATP and ADP levels until stress or nutrient
      deprivation stimulates a rapid burst of nucleotide release. Reducing the levels
      of media serum or glucose has no effect on ATP levels, but stimulates ADP release
      by up to 10-fold. Extracellular ADP is then metabolized or degraded and media ADP
      levels fall to basal levels within 2-4 h. Nucleotide release from hepatic cells
      is stimulated by the Ca(2+) ionophore, ionomycin, and by the P2 receptor agonist,
      2'3'-O-(4-benzoyl-benzoyl)-adenosine 5'-triphosphate (BzATP). Ionomycin (10 MUM)
      has a minimal effect on ATP release, but doubles media ADP levels at 5 min. In
      contrast, BzATP (10-100 MUM) increases both ATP and ADP levels by over 100-fold
      at 5 min. Ion channel purinergic receptor P2X7 and P2X4 gene silencing with small
      interference RNA (siRNA) and treatment with the P2X inhibitor, A438079 (100 MUM),
      decrease ADP release from hepatic cells, but have no effect on ATP. P2X
      inhibitors and siRNA have no effect on BzATP-stimulated nucleotide release. ADP
      release from human hepatic carcinoma cells is therefore regulated by P2X
      receptors and intracellular Ca(2+) levels. Extracellular ADP levels increase as a
      consequence of a cellular stress response resulting from serum or glucose
      deprivation. 

PMID- 25059925
TI  - Quantification of valproic acid in dried blood spots.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) of the antiepileptic drug valproic
      acid (VPA) is recommended in patients with multiple drug therapy or with
      concomitant disabilities to ensure treatment efficacy and avoid adverse reactions
      in both adults and children. The use of sampling techniques compatible with home
      sampling, such as dried blood spot sampling could potentially facilitate this for
      patients. AIM. To assess the usefulness of a bioanalytical method for
      quantification of VPA in dried blood spots. MATERIALS AND METHODS: Quantification
      was based on liquid chromatography-mass spectrometry (LC-MS), both for the DBS
      method and the plasma-based reference method. RESULTS: The method was validated
      in the range 10-1200 MUmol/L. Total imprecision ranged from 4.9-8.9 (%CV) and
      accuracy was within +/- 14%. CONCLUSION: The validated method has potential for
      evaluation in therapeutic drug monitoring in combination with home sampling of
      DBS. The impact of spot size can be controlled through acceptance criteria and
      hematocrit in the range 30-60% can be accepted in sampling. Comparison of VPA
      levels between plasma and whole blood cannot be done without considering the
      blood-plasma ratio.

PMID- 25059926
TI  - TNF alpha G308A gene polymorphism has an impact on renal function, microvascular
      permeability, organ involvement and severity of preeclampsia.
AB  - BACKGROUND/AIMS: Preeclampsia (PE) is a life-threatening complication of
      pregnancy that is associated with a high rate of maternal and perinatal morbidity
      and/or mortality worldwide. If untreated, it can progress to eclampsia, which can
      result in the death of the mother, the fetus or both. The etiology of PE is still
      uncertain; however, recently the role of the immune system has gained in
      importance. The role of tumor necrosis factor-alpha (TNF-alpha), a cytokine
      involved in inflammation processes, has been widely investigated in obstetric
      disorders. The aims of the present study were to investigate the effect of TNF
      alpha gene G308A (rs1800629) polymorphism on disease risk, renal function,
      microvascular permeability, endothelial cell dysfunction and organ involvement in
      women with PE. METHODS: Initially, 102 3rd-trimester pregnant women (preeclamptic
      cases and healthy controls) with singleton pregnancy were invited for
      participation, of which 76 were genotyped for TNF-alpha G308A polymorphism and
      evaluated for plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM
      1), fibronectin and TNF-alpha, which were tested for correlations with the
      profile of PE. The odds ratio (OR) and 95% confidence intervals obtained from
      unconditional logistic regression were used to test the association between the
      TNF-alpha polymorphism and PE risk. For continuous variables, we applied
      Student's t test and, for categorical variables, the Pearson chi(2) or Fisher's
      exact test. The two-way ANOVA test with Bonferroni correction was used in
      multivariate analyses. RESULTS: The A allele was more frequent in cases than
      controls (22.4 vs. 13.2%), which increased disease risk (OR = 2.73). Maternal
      serum levels of TNF-alpha, sVCAM-1 and fibronectin were significantly increased
      in cases (855.8 +/- 385.1 pg/ml, 1,243 +/- 671 ng/ml, 0.308 +/- 0.231 g/l,
      respectively) compared to controls (301.1 +/- 156.1 pg/ml, 651 +/- 250 ng/ml,
      0.218 +/- 0.101 g/l, respectively; p < 0.0001, p < 0.0001 and p = 0.031,
      respectively), and these levels showed an increasing trend with the mutant allele
      genotype. Moderate and severe proteinuria was higher in rs1800629 allele A
      subjects compared to G/G carriers (53.8 vs. 14.3% (p < 0.05) and 13.0 vs. 4.7% (p
      < 0.01), respectively). The adverse effect of rs1800629 allele A on renal
      function was confirmed by increased plasma creatine levels, urinary protein
      excretion and lower tubular resorption rate in preeclamptic patients. Moreover,
      rs1800629 allele A preeclamptic carriers showed higher serum levels of
      fibronectin and sVCAM-1 compared to G/G homozygotes. CONCLUSION: This study
      reveals a possible association between clinical and laboratory manifestations of
      PE and the TNF-alpha gene G308A (rs1800629) polymorphism.

PMID- 25059928
TI  - National Pain Strategy Task Force: the strategic plan for the IOM Pain Report.

PMID- 25059927
TI  - Risk score to predict gastrointestinal bleeding after acute ischemic stroke.
AB  - BACKGROUND: Gastrointestinal bleeding (GIB) is a common and often serious
      complication after stroke. Although several risk factors for post-stroke GIB have
      been identified, no reliable or validated scoring system is currently available
      to predict GIB after acute stroke in routine clinical practice or clinical
      trials. In the present study, we aimed to develop and validate a risk model
      (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB
      score) to predict in-hospital GIB after acute ischemic stroke. METHODS: The AIS
      GIB score was developed from data in the China National Stroke Registry (CNSR).
      Eligible patients in the CNSR were randomly divided into derivation (60%) and
      internal validation (40%) cohorts. External validation was performed using data
      from the prospective Chinese Intracranial Atherosclerosis Study (CICAS).
      Independent predictors of in-hospital GIB were obtained using multivariable
      logistic regression in the derivation cohort, and beta-coefficients were used to
      generate point scoring system for the AIS-GIB. The area under the receiver
      operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit
      test were used to assess model discrimination and calibration, respectively.
      RESULTS: A total of 8,820, 5,882, and 2,938 patients were enrolled in the
      derivation, internal validation and external validation cohorts. The overall in
      hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and
      external validation cohort, respectively. An 18-point AIS-GIB score was developed
      from the set of independent predictors of GIB including age, gender, history of
      hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke
      dependence, admission National Institutes of Health stroke scale score, Glasgow
      Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good
      discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95%
      CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts. The AIS
      GIB score was well calibrated in the derivation (P = 0.42), internal (P = 0.45)
      and external (P = 0.86) validation cohorts. CONCLUSION: The AIS-GIB score is a
      valid clinical grading scale to predict in-hospital GIB after AIS. Further
      studies on the effect of the AIS-GIB score on reducing GIB and improving outcome
      after AIS are warranted.

PMID- 25059929
TI  - Psychosocial aspects in cardiac rehabilitation: From theory to practice. A
      position paper from the Cardiac Rehabilitation Section of the European
      Association of Cardiovascular Prevention and Rehabilitation of the European
      Society of Cardiology.
AB  - A large body of empirical research shows that psychosocial risk factors (PSRFs)
      such as low socio-economic status, social isolation, stress, type-D personality,
      depression and anxiety increase the risk of incident coronary heart disease (CHD)
      and also contribute to poorer health-related quality of life (HRQoL) and
      prognosis in patients with established CHD. PSRFs may also act as barriers to
      lifestyle changes and treatment adherence and may moderate the effects of cardiac
      rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction
      between PSRFs and the cardiovascular system. Stress, anxiety and depression
      affect the cardiovascular system through immune, neuroendocrine and behavioural
      pathways. In turn, CHD and its associated treatments may lead to distress in
      patients, including anxiety and depression. In clinical practice, PSRFs can be
      assessed with single-item screening questions, standardised questionnaires, or
      structured clinical interviews. Psychotherapy and medication can be considered to
      alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a
      definite beneficial effect on cardiac endpoints is inconclusive. A multimodal
      behavioural intervention, integrating counselling for PSRFs and coping with
      illness should be included within comprehensive CR. Patients with clinically
      significant symptoms of distress should be referred for psychological counselling
      or psychologically focused interventions and/or psychopharmacological treatment.
      To conclude, the success of CR may critically depend on the interdependence of
      the body and mind and this interaction needs to be reflected through the
      assessment and management of PSRFs in line with robust scientific evidence, by
      trained staff, integrated within the core CR team. 

PMID- 25059930
TI  - Performance of the CHARGE-AF risk model for incident atrial fibrillation in the
      EPIC Norfolk cohort.
AB  - BACKGROUND: Identification of individuals at risk for developing atrial
      fibrillation (AF) will help to target screening and preventive interventions. We
      aimed to validate the CHARGE-AF model (including variables age, race, height,
      weight, blood pressure, smoking, antihypertensive medication, diabetes,
      myocardial infarction and heart failure) for prediction of five-year incident AF
      in a representative European population with a wide age range. METHODS AND
      RESULTS: The CHARGE-AF model was calculated in 24,020 participants of the
      population-based EPIC Norfolk study with 236 cases of hospitalization with
      diagnosis of AF within five years. The model showed good discrimination (c
      statistic 0.81, 95% confidence interval (CI) 0.75-0.85), but weak calibration
      (Chi(2)-statistic 142) with an almost two-fold overestimation of AF incidence. A
      recalibration to characteristics of the European Prospective Investigation into
      Cancer and Nutrition (EPIC) Norfolk cohort improved calibration considerably
      (Chi(2)-statistic 13.3), with acceptable discrimination in participants both >65
      and <=65 years of age (c-statistics 0.70, 95% CI 0.61-0.77 and 0.83, 95% CI 0.74
      0.88). The recalibrated model also showed good discrimination in participants
      free of cardiovascular disease (c-statistics 0.80, 95% CI 0.75-0.84). Categories
      of predicted risk (<2.5%, 2.5-5% or >5%) showed good concordance with observed
      five-year AF incidence of 0.62%, 3.49% and 8.74% (log rank test p < 0.001),
      respectively. CONCLUSION: A recalibration of the CHARGE-AF model is necessary for
      accurate predictions of five-year risk of AF in the EPIC Norfolk population. The
      recalibrated model showed good discrimination across a wide age range and in
      individuals free of cardiovascular disease, and hence is broadly applicable in
      primary care to identify people at risk for development of AF.

PMID- 25059931
TI  - Quantifying the benefits of achieving or maintaining long-term low risk profile
      for cardiovascular disease: The Doetinchem Cohort Study.
AB  - BACKGROUND: Studies investigating the relation between risk profiles and
      cardiovascular disease have measured risk at baseline only. We investigated
      maintenance and changes of risk profiles over time and their potential impact on
      incident cardiovascular disease. DESIGN: Population-based cohort study. METHODS:
      Risk factors were measured at baseline (1987-1991) among 5574 cardiovascular
      disease-free adults aged 20-59 years. They were classified into four risk
      categories according to smoking status, presence of diabetes and widely accepted
      cut-off values for blood pressure, total cholesterol/HDL-ratio and body mass
      index. Categories were subdivided (maintenance, deterioration, improvement) based
      on risk factor levels at six and 11 years of follow-up. Multivariable-adjusted
      hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular
      disease incidence 5-10 years following the risk-change period were fitted using
      Cox proportional hazards models. RESULTS: Only 12% of participants were low risk
      at baseline, and only 7% maintained it. Participants who maintained a low risk
      profile over 11 years had seven times lower risk of cardiovascular disease (HR:
      0.14, 95% CI: 0.05-0.41) than participants with long-term high risk profile,
      whereas those low risk at baseline whose profile deteriorated had three times
      lower risk (HR: 0.36, 95% CI: 0.18-0.71). Our results suggest that, within each
      baseline risk profile group, compared with a stable profile, improving profiles
      may be associated with up to two-fold lower HRs, and deteriorating profiles with
      about two-fold higher HRs. CONCLUSIONS: Our study, using long-term risk profiles,
      demonstrates the full benefits of low risk profile. These findings underscore the
      importance of achieving and maintaining low risk from young adulthood onwards.

PMID- 25059932
TI  - Factors influencing return-to-work after cerebrovascular disease: the importance
      of previous cardiovascular risk.
AB  - BACKGROUND: The role of prior cardiovascular risk (CVR) in the multifactorial
      process of returning to work after a cerebrovascular event has not been
      adequately investigated. Therefore, the objective of the present study was to
      analyse the association between previous CVR level, cardiovascular risk factors
      (CVRFs) and return-to-work (RTW) following cerebrovascular disease. DESIGN: This
      was a prospective observational study. METHODS: We analysed a cohort of 348
      patients who had experienced an episode of cerebrovascular disease-related work
      absence. These individuals were selected from the ICARIA study (Ibermutuamur
      CArdiovascular RIsk Assessment). Global CVR was assessed using the SCORE system.
      We investigated the association between demographics, work-related variables,
      CVRFs and RTW following a cerebrovascular event. RESULTS: We found that a total
      of 254 individuals (73.0%; 95% CI: 68.3-77.7) returned to work after
      cerebrovascular disease. Also, we observed a median loss of 12 working years due
      to disability. Moreover, adjusting for potential confounders revealed that low
      CVR level and the absence of the following CVRFs was associated with a higher
      likelihood of RTW: low vs moderate-to-high CVR level (OR: 2.55; 95% CI: 1.42
      4.57), no hypertension before stroke (OR: 1.95; 95% CI: 1.11-3.41), non-smoker
      status (OR: 2.26; 95% CI: 1.30-3.93) and no previous diabetes (OR: 2.46; 95% CI:
      1.26-4.79). CONCLUSIONS: Low CVR, along with the absence of several CVRFs, can be
      used to predict RTW rates following cerebrovascular events. Therefore,
      controlling hypertension, tobacco consumption and diabetes might contribute to
      the effectiveness of multidisciplinary rehabilitation and/or secondary/tertiary
      prevention programs for cerebrovascular disease.

PMID- 25059933
TI  - Perceived social support following myocardial infarction and long-term
      development of frailty.
AB  - AIM: Frailty is a multidimensional geriatric syndrome that indicates increasing
      vulnerability and decreasing resistance to stressors. Social support (SS) is
      linked both to cardiovascular disease and to frailty. However, few cohort studies
      evaluated SS as a potential predictor of frailty, and none involved coronary
      disease populations. The aim of this study was to evaluate the role of perceived
      SS (PSS) - a specific component of SS - in the prediction of frailty development
      in myocardial infarction (MI) survivors, controlling for other psychosocial risk
      factors. METHOD: A cohort of 558 patients aged <=65 years, admitted for first
      ever MI to hospitals in central Israel, was studied. PSS and other clinical and
      sociodemographic variables were assessed at baseline. Frailty was assessed via a
      frailty index of deficit accumulation 10-13 years later. Logistic regression
      models were constructed to assess the odds ratios (OR) for frailty associated
      with PSS as well as other covariates. RESULTS: At last follow-up, 154 (28%) met
      the criteria for frailty. In the logistic regression models, higher PSS level was
      associated with lower frailty risk (unadjusted OR = 0.63, 95%CI 0.53-0.76;
      multivariable-adjusted OR = 0.80, 95%CI 0.64-0.98). Below average family income,
      poor self-rated health and higher depression scores were all associated with the
      development of frailty, in both the unadjusted and adjusted models. CONCLUSIONS:
      PSS predicts frailty development post-MI, which has important implications for
      prognosis and healthcare use.

PMID- 25059934
TI  - Prognostic impact of abdominal fat distribution and cardiorespiratory fitness in
      asymptomatic type 2 diabetics.
AB  - BACKGROUND: Impaired cardiorespiratory fitness (CRF) is a potent risk factor for
      mortality in diabetes, and may modify the relation between adiposity and
      mortality. We evaluated the interaction between CRF and abdominal adiposity
      distribution with all-cause mortality, myocardial infarction or stroke in
      patients with diabetes. METHODS: We studied 294 type 2 diabetics without known
      coronary artery disease. CRF was quantified in metabolic equivalents by maximal
      treadmill testing, and categorized as low CRF (first tertile) or high CRF (second
      and third tertiles). Abdominal fat was quantified as subcutaneous or visceral
      adipose tissue from non-enhanced computed tomography scans. Association of CRF,
      adiposity distribution and their interaction with all-cause mortality, myocardial
      infarction or stroke was assessed by Cox proportional-hazard models. RESULTS:
      There were 31 (11%) events during 62 +/- 12 months. Low CRF was significantly
      associated with event risk before and after adjustment for each measure of
      adiposity (hazard ratio 3.79, 95% confidence interval 1.79-8.01, p < 0.001). CRF
      level was inversely correlated with subcutaneous (r = -0.44, p < 0.001) but not
      visceral adipose tissue (r = -0.06, p = 0.31). Absolute event rates increased
      progressively across visceral adipose tissue tertiles, but decreased across
      subcutaneous tertiles. However, within each tertile of both adiposity measures,
      increased events were observed in the low compared with the high CRF group; this
      trend was also observed in an adjusted multivariate proportional hazards model.
      CONCLUSIONS: Although subcutaneous and visceral adipose tissues differed in their
      association with CRF levels and absolute event rates, lower baseline CRF in type
      2 diabetics was significantly associated with higher risk of all-cause mortality,
      myocardial infarction or stroke, regardless of abdominal adiposity pattern.

PMID- 25059935
TI  - Neutrophil-lymphocyte ratio may predict in-hospital mortality in patients with
      acute type A aortic dissection.
AB  - INTRODUCTION: Inflammation has been reported to be associated with aortic
      dissection (AD), from the development to the prognosis of AD. In this study we
      aimed to find the role of the neutrophil-lymphocyte ratio (NLR) in the prediction
      of clinical events in patients with acute AD type A. PATIENTS AND METHODS: The
      study comprised 37 patients who were hospitalized at our center between 2009 and
      2013 with the diagnosis of acute AD type A. RESULTS: The mean NLR was
      significantly higher in patients with pericardial effusion than those without
      effusion (15.6 +/- 11.4 vs. 7.5 +/- 4.8, p = 0.005). An NLR value > 8.51 yielded
      an area under the curve (AUC) value of 0.829 [95 % confidence interval (CI) 0.674
      0.984, p = 0.004], which demonstrated a sensitivity of 77 % and specificity of 74
      % for the prediction of mortality. CONCLUSIONS: The novel inflammatory marker NLR
      could be used to predict pericardial effusion and in-hospital mortality in
      patients with acute AD type A.

PMID- 25059937
TI  - Bringing sex workers to the centre of the HIV response.

PMID- 25059938
TI  - A community empowerment approach to the HIV response among sex workers:
      effectiveness, challenges, and considerations for implementation and scale-up.
AB  - A community empowerment-based response to HIV is a process by which sex workers
      take collective ownership of programmes to achieve the most effective HIV
      outcomes and address social and structural barriers to their overall health and
      human rights. Community empowerment has increasingly gained recognition as a key
      approach for addressing HIV in sex workers, with its focus on addressing the
      broad context within which the heightened risk for infection takes places in
      these individuals. However, large-scale implementation of community empowerment
      based approaches has been scarce. We undertook a comprehensive review of
      community empowerment approaches for addressing HIV in sex workers. Within this
      effort, we did a systematic review and meta-analysis of the effectiveness of
      community empowerment in sex workers in low-income and middle-income countries.
      We found that community empowerment-based approaches to addressing HIV among sex
      workers were significantly associated with reductions in HIV and other sexually
      transmitted infections, and with increases in consistent condom use with all
      clients. Despite the promise of a community-empowerment approach, we identified
      formidable structural barriers to implementation and scale-up at various levels.
      These barriers include regressive international discourses and funding
      constraints; national laws criminalising sex work; and intersecting social
      stigmas, discrimination, and violence. The evidence base for community
      empowerment in sex workers needs to be strengthened and diversified, including
      its role in aiding access to, and uptake of, combination interventions for HIV
      prevention. Furthermore, social and political change are needed regarding the
      recognition of sex work as work, both globally and locally, to encourage
      increased support for community empowerment responses to HIV. 

PMID- 25059940
TI  - Steffanie Strathdee: "called" to HIV prevention.

PMID- 25059939
TI  - Male sex workers: practices, contexts, and vulnerabilities for HIV acquisition
      and transmission.
AB  - Male sex workers who sell or exchange sex for money or goods encompass a very
      diverse population across and within countries worldwide. Information
      characterising their practices, contexts where they live, and their needs is
      limited, because these individuals are generally included as a subset of larger
      studies focused on gay men and other men who have sex with men (MSM) or even
      female sex workers. Male sex workers, irrespective of their sexual orientation,
      mostly offer sex to men and rarely identify as sex workers, using local or
      international terms instead. Growing evidence indicates a sustained or increasing
      burden of HIV among some male sex workers within the context of the slowing
      global HIV pandemic. Several synergistic facilitators could be potentiating HIV
      acquisition and transmission among male sex workers, including biological,
      behavioural, and structural determinants. Criminalisation and intersectional
      stigmas of same-sex practices, commercial sex, and HIV all augment risk for HIV
      and sexually transmitted infections among male sex workers and reduce the
      likelihood of these people accessing essential services. These contexts, taken
      together with complex sexual networks among male sex workers, define this group
      as a key population underserved by current HIV prevention, treatment, and care
      services. Dedicated efforts are needed to make those services available for the
      sake of both public health and human rights. Evidence-based and human rights
      affirming services dedicated specifically to male sex workers are needed to
      improve health outcomes for these men and the people within their sexual
      networks. 

PMID- 25059941
TI  - HIV risk and preventive interventions in transgender women sex workers.
AB  - Worldwide, transgender women who engage in sex work have a disproportionate risk
      for HIV compared with natal male and female sex workers. We reviewed recent
      epidemiological research on HIV in transgender women and show that transgender
      women sex workers (TSW) face unique structural, interpersonal, and individual
      vulnerabilities that contribute to risk for HIV. Only six studies of evidence
      based prevention interventions were identified, none of which focused exclusively
      on TSW. We developed a deterministic model based on findings related to HIV risks
      and interventions. The model examines HIV prevention approaches in TSW in two
      settings (Lima, Peru and San Francisco, CA, USA) to identify which interventions
      would probably achieve the UN goal of 50% reduction in HIV incidence in 10 years.
      A combination of interventions that achieves small changes in behaviour and low
      coverage of biomedical interventions was promising in both settings, suggesting
      that the expansion of prevention services in TSW would be highly effective.
      However, this expansion needs appropriate sustainable interventions to tackle the
      upstream drivers of HIV risk and successfully reach this population. Case studies
      of six countries show context-specific issues that should inform development and
      implementation of key interventions across heterogeneous settings. We summarise
      the evidence and knowledge gaps that affect the HIV epidemic in TSW, and propose
      a research agenda to improve HIV services and policies for this population. 

PMID- 25059942
TI  - Combination HIV prevention for female sex workers: what is the evidence?
AB  - Sex work occurs in many forms and sex workers of all genders have been affected
      by HIV epidemics worldwide. The determinants of HIV risk associated with sex work
      occur at several levels, including individual biological and behavioural, dyadic
      and network, and community and social environmental levels. Evidence indicates
      that effective HIV prevention packages for sex workers should include
      combinations of biomedical, behavioural, and structural interventions tailored to
      local contexts, and be led and implemented by sex worker communities. A model
      simulation based on the South African heterosexual epidemic suggests that condom
      promotion and distribution programmes in South Africa have already reduced HIV
      incidence in sex workers and their clients by more than 70%. Under optimistic
      model assumptions, oral pre-exposure prophylaxis together with test and treat
      programmes could further reduce HIV incidence in South African sex workers and
      their clients by up to 40% over a 10-year period. Combining these biomedical
      approaches with a prevention package, including behavioural and structural
      components as part of a community-driven approach, will help to reduce HIV
      infection in sex workers in different settings worldwide. 

PMID- 25059944
TI  - Why are sex workers who use substances at risk for HIV?

PMID- 25059945
TI  - Trafficking, sex work, and HIV: efforts to resolve conflicts.

PMID- 25059943
TI  - Human rights violations against sex workers: burden and effect on HIV.
AB  - We reviewed evidence from more than 800 studies and reports on the burden and HIV
      implications of human rights violations against sex workers. Published research
      documents widespread abuses of human rights perpetrated by both state and non
      state actors. Such violations directly and indirectly increase HIV
      susceptibility, and undermine effective HIV-prevention and intervention efforts.
      Violations include homicide; physical and sexual violence, from law enforcement,
      clients, and intimate partners; unlawful arrest and detention; discrimination in
      accessing health services; and forced HIV testing. Abuses occur across all policy
      regimes, although most profoundly where sex work is criminalised through punitive
      law. Protection of sex workers is essential to respect, protect, and meet their
      human rights, and to improve their health and wellbeing. Research findings affirm
      the value of rights-based HIV responses for sex workers, and underscore the
      obligation of states to uphold the rights of this marginalised population. 

PMID- 25059946
TI  - Time for a revolution in reporting of global health data.

PMID- 25059948
TI  - Dispelling myths about sex workers and HIV.

PMID- 25059947
TI  - Global epidemiology of HIV among female sex workers: influence of structural
      determinants.
AB  - Female sex workers (FSWs) bear a disproportionately large burden of HIV infection
      worldwide. Despite decades of research and programme activity, the epidemiology
      of HIV and the role that structural determinants have in mitigating or
      potentiating HIV epidemics and access to care for FSWs is poorly understood. We
      reviewed available published data for HIV prevalence and incidence, condom use,
      and structural determinants among this group. Only 87 (43%) of 204 unique studies
      reviewed explicitly examined structural determinants of HIV. Most studies were
      from Asia, with few from areas with a heavy burden of HIV such as sub-Saharan
      Africa, Russia, and eastern Europe. To further explore the potential effect of
      structural determinants on the course of epidemics, we used a deterministic
      transmission model to simulate potential HIV infections averted through
      structural changes in regions with concentrated and generalised epidemics, and
      high HIV prevalence among FSWs. This modelling suggested that elimination of
      sexual violence alone could avert 17% of HIV infections in Kenya (95% uncertainty
      interval [UI] 1-31) and 20% in Canada (95% UI 3-39) through its immediate and
      sustained effect on non-condom use) among FSWs and their clients in the next
      decade. In Kenya, scaling up of access to antiretroviral therapy among FSWs and
      their clients to meet WHO eligibility of a CD4 cell count of less than 500 cells
      per MUL could avert 34% (95% UI 25-42) of infections and even modest coverage of
      sex worker-led outreach could avert 20% (95% UI 8-36) of infections in the next
      decade. Decriminalisation of sex work would have the greatest effect on the
      course of HIV epidemics across all settings, averting 33-46% of HIV infections in
      the next decade. Multipronged structural and community-led interventions are
      crucial to increase access to prevention and treatment and to promote human
      rights for FSWs worldwide. 

PMID- 25059951
TI  - Responses to HIV in sexually exploited children or adolescents who sell sex.

PMID- 25059950
TI  - An action agenda for HIV and sex workers.
AB  - The women, men, and transgender people who sell sex globally have
      disproportionate risks and burdens of HIV in countries of low, middle, and high
      income, and in concentrated and generalised epidemic contexts. The greatest HIV
      burdens continue to be in African female sex workers. Worldwide, sex workers
      still face reduced access to needed HIV prevention, treatment, and care services.
      Legal environments, policies, police practices, absence of funding for research
      and HIV programmes, human rights violations, and stigma and discrimination
      continue to challenge sex workers' abilities to protect themselves, their
      families, and their sexual partners from HIV. These realities must change to
      realise the benefits of advances in HIV prevention and treatment and to achieve
      global control of the HIV pandemic. Effective combination prevention and
      treatment approaches are feasible, can be tailored for cultural competence, can
      be cost-saving, and can help to address the unmet needs of sex workers and their
      communities in ways that uphold their human rights. To address HIV in sex workers
      will need sustained community engagement and empowerment, continued research,
      political will, structural and policy reform, and innovative programmes. But such
      actions can and must be achieved for sex worker communities everywhere. 

PMID- 25059952
TI  - Intrahepatic Cholestasis of Pregnancy: mRNAs for LIPF and ELOVL4 Genes Are Not
      Detectable in Circulating Maternal Plasma.

PMID- 25059953
TI  - The double-edged sword of electronic health records: implications for patient
      disclosure.
AB  - OBJECTIVE: Electronic health record (EHR) systems are linked to improvements in
      quality of care, yet also privacy and security risks. Results from research
      studies are mixed about whether patients withhold personal information from their
      providers to protect against the perceived EHR privacy and security risks. This
      study seeks to reconcile the mixed findings by focusing on whether accounting for
      patients' global ratings of care reveals a relationship between EHR provider-use
      and patient non-disclosure. MATERIALS AND METHODS: A nationally representative
      sample from the 2012 Health Information National Trends Survey was analyzed using
      bivariate and multivariable logit regressions to examine whether global ratings
      of care suppress the relationship between EHR provider-use and patient non
      disclosure. RESULTS: 13% of respondents reported having ever withheld information
      from a provider because of privacy/security concerns. Bivariate analysis showed
      that withholding information was unrelated to whether respondents' providers used
      an EHR. Multivariable analysis showed that accounting for respondents' global
      ratings of care revealed a positive relationship between having a provider who
      uses an EHR and withholding information. DISCUSSION: After accounting for global
      ratings of care, findings suggest that patients may non-disclose to providers to
      protect against the perceived EHR privacy and security risks. Despite evidence
      that EHRs inhibit patient disclosure, their advantages for promoting quality of
      care may outweigh the drawbacks. CONCLUSIONS: Clinicians should leverage the
      EHR's value in quality of care and discuss patients' privacy concerns during
      clinic visits, while policy makers should consider how to address the real and
      perceived privacy and security risks of EHRs.

PMID- 25059954
TI  - Prevalence and correlates of a 'knee' pattern on the maximal expiratory flow
      volume loop in young adults.
AB  - BACKGROUND AND OBJECTIVE: Visual inspection of the maximal flow-volume curve is
      an important step in interpreting spirometry. Many young people have a convex
      inflection or 'knee' on the expiratory part of the loop. This is thought to be a
      normal variant, but this view is based on theoretical grounds, and the
      epidemiology of the knee pattern has never been reported. METHODS: Flow-volume
      loops from an unselected birth cohort of 1037 individuals at ages 18, 26, 32 and
      38 years were visually inspected for a knee pattern. Associations with asthma
      diagnoses, smoking history, body mass index (BMI) and spirometry were assessed.
      RESULTS: The knee pattern was found in approximately two thirds of men and women
      at age 18. The prevalence decreased with age, but it was more likely to persist
      in women. The knee was more common after bronchodilator and was associated with
      higher forced expiratory volume in 1 s/forced vital capacity ratios and mid
      expiratory flow rates. There was no association with smoking, except for an
      inverse correlation in men at age 18. No association was found with BMI. Women
      with asthma were less likely to have a knee at both ages 18 and 38, whereas men
      with asthma showed an inverse association at age 18. CONCLUSIONS: A knee is a
      very common pattern on flow-volume loop in young adults. In accordance with
      theoretical predictions, the prevalence of the knee declines with age, but it is
      more likely to persist in women. It is associated with less airflow obstruction
      and is less common in people with asthma.

PMID- 25059955
TI  - Research councils unite to tackle antimicrobial resistance.

PMID- 25059957
TI  - Marking the end of an artistic residency.

PMID- 25059958
TI  - GM animals account for more than half of scientific procedures.

PMID- 25059956
TI  - Roundtable proposes a '3Rs' approach to use of antimicrobials.

PMID- 25059959
TI  - Timely recognition for conservation effort.

PMID- 25059960
TI  - Awards for outstanding contributions to animal welfare.

PMID- 25059961
TI  - One Health: time to move on from just talking.

PMID- 25059962
TI  - Taking the right track: new directions in veterinary education.

PMID- 25059963
TI  - Vaccination against tuberculosis in badgers and cattle: an overview of the
      challenges, developments and current research priorities in Great Britain.
AB  - Bovine tuberculosis (TB) is a significant threat to the cattle industry in
      England and Wales. It is widely acknowledged that a combination of measures
      targeting both cattle and wildlife will be required to eradicate bovine TB or
      reduce its prevalence until European official freedom status is achieved.
      Vaccination of cattle and/or badgers could contribute to bovine TB control in
      Great Britain, although there are significant gaps in our knowledge regarding the
      impact that vaccination would actually have on bovine TB incidence. Laboratory
      studies have demonstrated that vaccination with BCG can reduce the progression
      and severity of TB in both badgers and cattle. This is encouraging in terms of
      the prospect of a sustained vaccination programme achieving reductions in disease
      prevalence; however, developing vaccines for tackling the problem of bovine TB is
      challenging, time-consuming and resource-intensive, as this review article sets
      out to explain. 

PMID- 25059964
TI  - Potential pathway for Crimean Congo haemorrhagic fever virus to enter the UK.

PMID- 25059965
TI  - Launch of a voluntary camelid TB scheme.

PMID- 25059966
TI  - Consolidation of practice.

PMID- 25059949
TI  - Global, regional, and national incidence and mortality for HIV, tuberculosis, and
      malaria during 1990-2013: a systematic analysis for the Global Burden of Disease
      Study 2013.
AB  - BACKGROUND: The Millennium Declaration in 2000 brought special global attention
      to HIV, tuberculosis, and malaria through the formulation of Millennium
      Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a
      consistent and comprehensive approach to disease estimation for between 1990 and
      2013, and an opportunity to assess whether accelerated progress has occured since
      the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV,
      we used the UNAIDS Spectrum model appropriately modified based on a systematic
      review of available studies of mortality with and without antiretroviral therapy
      (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital
      registration data corrected for misclassification of HIV deaths. In generalised
      epidemics, we minimised a loss function to select epidemic curves most consistent
      with prevalence data and demographic data for all-cause mortality. We analysed
      counterfactual scenarios for HIV to assess years of life saved through prevention
      of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed
      vital registration and verbal autopsy data to estimate mortality using cause of
      death ensemble modelling. We analysed data for corrected case-notifications,
      expert opinions on the case-detection rate, prevalence surveys, and estimated
      cause-specific mortality using Bayesian meta-regression to generate consistent
      trends in all parameters. We analysed malaria mortality and incidence using an
      updated cause of death database, a systematic analysis of verbal autopsy
      validation studies for malaria, and recent studies (2010-13) of incidence, drug
      resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in
      2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7
      million to 2.1 million), 29.2 million prevalent HIV cases (28.1 to 31.7), and 1.3
      million HIV deaths (1.3 to 1.5). At the peak of the epidemic in 2005, HIV caused
      1.7 million deaths (1.6 million to 1.9 million). Concentrated epidemics in Latin
      America and eastern Europe are substantially smaller than previously estimated.
      Through interventions including PMTCT and ART, 19.1 million life-years (16.6
      million to 21.5 million) have been saved, 70.3% (65.4 to 76.1) in developing
      countries. From 2000 to 2011, the ratio of development assistance for health for
      HIV to years of life saved through intervention was US$4498 in developing
      countries. Including in HIV-positive individuals, all-form tuberculosis incidence
      was 7.5 million (7.4 million to 7.7 million), prevalence was 11.9 million (11.6
      million to 12.2 million), and number of deaths was 1.4 million (1.3 million to
      1.5 million) in 2013. In the same year and in only individuals who were HIV
      negative, all-form tuberculosis incidence was 7.1 million (6.9 million to 7.3
      million), prevalence was 11.2 million (10.8 million to 11.6 million), and number
      of deaths was 1.3 million (1.2 million to 1.4 million). Annualised rates of
      change (ARC) for incidence, prevalence, and death became negative after 2000.
      Tuberculosis in HIV-negative individuals disproportionately occurs in men and
      boys (versus women and girls); 64.0% of cases (63.6 to 64.3) and 64.7% of deaths
      (60.8 to 70.3). Globally, malaria cases and deaths grew rapidly from 1990
      reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1.2
      million deaths (1.1 million to 1.4 million) in 2004. Since 2004, child deaths
      from malaria in sub-Saharan Africa have decreased by 31.5% (15.7 to 44.1).
      Outside of Africa, malaria mortality has been steadily decreasing since 1990.
      INTERPRETATION: Our estimates of the number of people living with HIV are 18.7%
      smaller than UNAIDS's estimates in 2012. The number of people living with malaria
      is larger than estimated by WHO. The number of people living with HIV,
      tuberculosis, or malaria have all decreased since 2000. At the global level,
      upward trends for malaria and HIV deaths have been reversed and declines in
      tuberculosis deaths have accelerated. 101 countries (74 of which are developing)
      still have increasing HIV incidence. Substantial progress since the Millennium
      Declaration is an encouraging sign of the effect of global action. FUNDING: Bill
      & Melinda Gates Foundation.

PMID- 25059967
TI  - Assessing the association of oxytocin augmentation with obstetric anal sphincter
      injury in nulliparous women: a population-based, case-control study.
AB  - OBJECTIVE: To assess the association of oxytocin augmentation with obstetric anal
      sphincter injury among nulliparous women. DESIGN: Population-based, case-control
      study. SETTING: Primary and secondary teaching hospital serving a Norwegian
      region. POPULATION: 15 476 nulliparous women with spontaneous start of labour,
      single cephalic presentation and gestation >=37 weeks delivering vaginally
      between 1999 and 2012. METHODS: Based on the presence or absence of oxytocin
      augmentation, episiotomy, operative vaginal delivery and birth weight (<4000 vs
      >=4000 g), we modelled in logistic regression the best fit for prediction of anal
      sphincter injury. Within the modified model of main exposures, we tested for
      possible confounding, and interactions between maternal age, ethnicity, occiput
      posterior position and epidural analgaesia. MAIN OUTCOME MEASURE: Obstetric anal
      sphincter injury. RESULTS: Oxytocin augmentation was associated with a higher OR
      of obstetric anal sphincter injuries in women giving spontaneous birth to infants
      weighing <4000 g (OR 1.8; 95% CI 1.5 to 2.2). Episiotomy was not associated with
      sphincter injuries in spontaneous births, but with a lower OR in operative
      vaginal deliveries. Spontaneous delivery of infants weighing >=4000 g was
      associated with a threefold higher OR, and epidural analgaesia was associated
      with a 30% lower OR in comparison to no epidural analgaesia. CONCLUSIONS:
      Oxytocin augmentation was associated with a higher OR of obstetric anal sphincter
      injuries during spontaneous deliveries of normal-size infants. We observed a
      considerable effect modification between the most important factors predicting
      anal sphincter injuries in the active second stage of labour.

PMID- 25059968
TI  - Risk factors for bloodborne viral hepatitis in healthcare workers of Pakistan: a
      population based case-control study.
AB  - OBJECTIVES: A high prevalence of viral hepatitis B and C was found among
      healthcare workers during a province-wide screening in Sindh Province, Pakistan.
      A follow-up study was undertaken to identify risk factors for this high
      prevalence in healthcare workers. DESIGN: Population based case-control design.
      SETTING: Public sector healthcare facilities in a rural district of Pakistan.
      PARTICIPANTS: Healthcare workers who were screened for hepatitis B surface
      antigen (HBsAg) and hepatitis C virus (HCV) antibodies. 178 healthcare workers
      employed at the public sector clinics and hospitals of the district were
      approached, of which 14 refused to participate. Cases had detectable serum
      antibodies against HCV and the presence of HBsAg. Healthcare workers non-reactive
      to HCV antibodies and with no HBsAg were controls. These were matched in a ratio
      of 1:1. OUTCOME MEASURE: Detectable serum HBsAg and HCV antibody titer were taken
      as outcome. OR for various exposures was calculated; those with p<0.25 were
      entered in a multivariate logistic regression model to find out significant
      predictors. RESULTS: Needle stick injury (OR=6; CI95 1.4 to 23), recapping the
      needle (OR=5.7; CI95 1.1 to 28), wound care at accident and emergency of a
      hospital (OR=5.5; CI95 1 to 28), female gender (OR=3.4; CI95 1 to 12) and more
      than 10 years of formal education (OR=0.25; CI95 0.07 to 0.8) were associated
      with hepatitis C. Hepatitis B was found to be associated with trying to bend or
      break a needle after use (OR=4.9; CI95 1 to 24). CONCLUSIONS: Healthcare workers
      in Pakistan are at additional risk of exposure to bloodborne pathogens. Bi
      dimensional risk factors present at individual and broader health systems levels
      are responsible. Occupational safety, health trainings and redesigning of the
      curriculum for allied health professionals are required.

PMID- 25059969
TI  - Education Against Tobacco (EAT): a quasi-experimental prospective evaluation of a
      programme for preventing smoking in secondary schools delivered by medical
      students: a study protocol.
AB  - INTRODUCTION: A survey conducted by the German Federal Centre for Health
      Education in 2012 showed that 35.2% of all young adults (18-25 years) and 12.0%
      of all adolescents (12-17 years) in Germany are regular cigarette smokers. Most
      smoked their first cigarette in early adolescence. We recently reported a
      significantly positive short-term effect of a physician-delivered school-based
      smoking prevention programme on the smoking behaviour of schoolchildren in
      Germany. However, physician-based programmes are usually very expensive.
      Therefore, we will evaluate and optimise Education against Tobacco (EAT), a
      widespread, low-cost programme delivered by about 400 medical students from 16
      universities in Germany. METHODS AND ANALYSIS: A prospective quasi-experimental
      study design with two measurements at baseline (t1) and 6 months post
      intervention (t2) to investigate an intervention in 10-15-year-olds in grades 6-8
      at German secondary schools. The intervention programme consists of two 60-min
      school-based medical-student-delivered modules with (module 1) and without the
      involvement of patients with tobacco-related diseases and control groups (no
      intervention). The study questionnaire measuring smoking status (water pipe and
      cigarette smoking), smoking-related cognitions, and gender, social and cultural
      aspects was designed and pre-tested in advance. The primary end point is the
      prevalence of smokers and non-smokers in the two study arms at 6 months after the
      intervention. The percentage of former smokers and new smokers in the two groups
      and the measures of smoking behaviour will be studied as secondary outcome
      measures. ETHICS AND DISSEMINATION: In accordance with Good Epidemiologic
      Practice (GEP) guidelines, the study protocol was submitted for approval by the
      responsible ethics committee, which decided that the study does not need ethical
      approval (Goethe University, Frankfurt-Main, Germany). Findings will be
      disseminated in peer-reviewed journals, at conferences, within our scientific
      advisory board and through medical students within the EAT project.

PMID- 25059970
TI  - Risk factors for bone metastasis in patients with primary lung cancer: study
      protocol for a systematic review.
AB  - INTRODUCTION: Bone metastasis (BM) in patients with primary lung cancer poses a
      serious health problem. Numerous risk factors have been hypothesised to predict
      BM in these patients, but research studies are of mutable quality, and may not be
      of value in clinical evaluation. METHODS AND ANALYSIS: We will search a number of
      electronic databases including PubMed, MEDLINE, Web of Science, EMBASE, the
      Cochrane Library (Cochrane Database of Systematic Reviews) and the Cochrane
      Central Register of Controlled Trials (CENTRAL). We will carry out a secondary
      search for articles from references of included articles (from January 1990 to
      June 2014). Primary and secondary outcomes will be BM and skeletal-related events
      information. We will summarise the effect estimates of risk factors and use
      random-effect models to pool the estimates, if the outcomes and characteristics
      in studies are comparable. The quality of the study will be assessed using the
      Newcastle-Ottawa Scale and the Cochrane Collaboration tool. TRIAL REGISTRATION
      NUMBER: CRD42013003744.

PMID- 25059972
TI  - Glioma tissue obtained by modern ultrasonic aspiration with a simple sterile
      suction trap for primary cell culture and pathological evaluation.
AB  - OBJECTIVES: Ultrasonic aspiration is widely used in the resection of brain
      tumors. Nevertheless, tumor tissue fragments obtained by ultrasonic aspiration
      are usually discarded. In this study, we demonstrate that these fragments are
      possible sources of material for histopathological study and tissue culture and
      compare their microscopic features and viability in tissue culture of cavitron
      ultrasonic surgical aspirator tissue fragments. METHODS: Brain tumor tissue
      collected by ultrasonic aspiration (CUSA EXcel(r); Integra Radionics Inc.) in a
      simple sterile suction trap during resection was processed for primary cell
      culture. Cell viability and immunohistological markers were measured by the WST-1
      test, microscopy and immunofluorescent evaluation. RESULTS: Six gliomas are
      presented to demonstrate that these tissue fragments show good preservation of
      histological detail and tissue viability in culture. CONCLUSION: Utilization of
      this material may facilitate pathological interpretation by providing a more
      representative sample of tumor histology as well as an adequate and sterile
      biosource of material for tissue culture studies.

PMID- 25059971
TI  - Extended-release nifedipine and the risk of intestinal obstruction: a population
      based study.
AB  - OBJECTIVES: To examine the risk of bowel obstruction in older adults during
      treatment with extended-release nifedipine compared with patients treated with
      amlodipine. DESIGN: Retrospective cohort study using multiple linked healthcare
      databases. SETTING: Ontario, Canada from 1 April 1997 to 31 December 2010.
      PARTICIPANTS: We identified patients aged 66 years and older who started
      treatment with Adalat XL, an extended-release nifedipine product employing a
      tablet delivery system associated with mechanical bowel obstruction. For
      comparison, we studied patients receiving amlodipine, a long-acting calcium
      channel blocker that does not utilise the same delivery system and has not been
      implicated as a cause of bowel obstruction. Propensity score matching was used to
      ensure similarity of patients receiving the two drugs. PRIMARY OUTCOME MEASURE:
      HR for the association between extended-release nifedipine relative to amlodipine
      and hospitalisation for bowel obstruction during therapy. RESULTS: Over the 13
      year study period, we identified 103 657 patients treated with extended-release
      nifedipine and 204 733 patients treated with amlodipine. In these two groups, 591
      (0.6%) and 1185 (0.6%) of patients were hospitalised for bowel obstruction,
      respectively. We found no difference in the risk of bowel obstruction among
      patients treated with extended-release nifedipine compared with amlodipine (HR
      1.09, 95% CI 0.96 to 1.24). CONCLUSIONS: Bowel obstruction during treatment with
      extended-release nidefipine is rare, and the risk is not appreciably greater than
      that during treatment with amlodipine.

PMID- 25059973
TI  - Zoledronic acid and irradiation in oral squamous cell carcinoma.
AB  - OBJECTIVE: This in vitro study evaluated cytotoxicity and cell migration effects
      of zoledronic acid and irradiation upon oral squamous cell carcinoma. MATERIALS
      AND METHODS: Zoledronic acid was administrated at doses of 10, 25, 50, and 100
      MUM to PE/CA-PJ15 oral squamous cell carcinoma cultures, irradiated with
      different doses (0, 5, 15, and 30 Gy), followed by evaluation of the effects on
      cell viability. Cell migration capacity was studied after 24- and 72-h
      incubation. RESULTS: At 24 h, the 100 MUM concentration of zoledronic acid
      combined with 15 Gy irradiation caused the greatest decrease in cell viability.
      At 72 h, statistically significant decreases in cell viability were found with
      all concentrations of zoledronic acid with or without irradiation: 0 Gy (P <
      0.001), 5 Gy (P < 0.001), 15 Gy (P < 0.001), and 30 Gy (P < 0.001). 50 MUM and
      100 MUM doses of zoledronic acid combined with 5 Gy irradiation yielded the
      greatest decrease in cell migration capacity. CONCLUSIONS: Zoledronic acid
      increases cytotoxic activity in the PE/CA-PJ15 cell line and reduces cell
      migration capacity. These findings suggest that combination therapy using
      biphosphates and radiation may offer a promising therapy.

PMID- 25059975
TI  - Postnatal maturation of skin barrier function in premature infants.
AB  - BACKGROUND: In preterm infants, skin barrier maturation entails regional
      variability. OBJECTIVES: To characterize postnatal skin barrier development in
      covered, uncovered and diapered regions in healthy premature infants over a
      longitudinal observation period. METHODS: Transepidermal water loss (TEWL),
      stratum corneum hydration (SCH), pH and sebum were measured at postnatal ages of
      1-7 days and 2-7 weeks on the forehead, abdomen, thigh and buttock of preterm
      infants (gestational age 30-37 weeks; n = 48) under monitored ambient conditions.
      A standard minimal skin care regimen was practised. RESULTS: TEWL increased
      significantly on the buttock (p = 0.007), while remaining stable on the forehead,
      abdomen and thigh. SCH and sebum remained stable in all studied body regions with
      increasing age. On the buttock, pH increased (p = 0.049), while other body
      regions exhibited a significant decrease (p <= 0.019). TEWL (p < 0.001) and SCH
      (p <= 0.002) revealed significantly higher values on the buttock, compared to
      other body regions. CONCLUSIONS: Stable TEWL, SCH and sebum values may indicate a
      lack of skin barrier maturation. Postnatal decrease in skin pH suggests an
      adaptation process with acid mantle formation. Differences in skin barrier
      development were observed between anatomical regions. SCH, TEWL and pH values
      demonstrated a distinct course in the diaper area, indicating an impaired skin
      barrier function in this region.

PMID- 25059976
TI  - How big is the bioenergy piece of the energy pie? Who cares--it's pie!

PMID- 25059974
TI  - Phytohormone mediation of interactions between herbivores and plant pathogens.
AB  - Induced plant defenses against either pathogens or herbivore attackers are
      regulated by phytohormones. These phytohormones are increasingly recognized as
      important mediators of interactions between organisms associated with plants. In
      this review, we discuss the role of plant defense hormones in sequential tri
      partite interactions among plants, pathogenic microbes, and herbivorous insects,
      based on the most recent literature. We discuss the importance of pathogen
      trophic strategy in the interaction with herbivores that exhibit different
      feeding modes. Plant resistance mechanisms also affect plant quality in future
      interactions with attackers. We discuss exemplary evidence for the hypotheses
      that (i) biotrophic pathogens can facilitate chewing herbivores, unless plants
      exhibit effector-triggered immunity, but (ii) facilitate or inhibit phloem
      feeders. (iii) Necrotrophic pathogens, on the other hand, can inhibit both phloem
      feeders and chewers. We also propose herbivore feeding mode as predictor of
      effects on pathogens of different trophic strategies, providing evidence for the
      hypotheses that (iv) phloem feeders inhibit pathogen attack by increasing SA
      induction, whereas (v) chewing herbivores tend not to affect necrotrophic
      pathogens, while they may either inhibit or facilitate biotrophic pathogens.
      Putting these hypotheses to the test will increase our understanding of
      phytohormonal regulation of plant defense to sequential attack by plant pathogens
      and insect herbivores. This will provide valuable insight into plant-mediated
      ecological interactions among members of the plant-associated community. 

PMID- 25059977
TI  - Facile preparation of boronic acid-functionalized magnetic nanoparticles with a
      high capacity and their use in the enrichment of cis-diol-containing compounds
      from plasma.
AB  - The use of bronate affinity adsorbents is a new separation method that appeared
      recently with great potential for specific extraction of cis-diol-containing
      compounds. In this work,a new strategy for the facile construction of boronic
      acid-functionalized Fe3 O4 magnetic nanoparticles (Fe3 O4 @FPBA MNPs) with a high
      capacity was described. The extraction capacity of the Fe3 O4 @FPBA MNPs was
      determined to be 66.0 +/- 2.7 umol/g for catechol and 80.6 +/- 2.0 umol/g for
      dopamine, being higher than that for the reported methods. The Fe3 O4 @FPBA MNPs
      were used to extract four cis-diol drugs: caffeic acid isopropyl ester, caffic
      acid bornyl ester, isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate and 3
      (3, 4-dihydroxyphenyl)-2-hydroxylpropionic acid - from the spiked rabbit plasma,
      and the recoveries of four drugs were between 87.29 and104.37% with relative
      standard deviations ranging from 1.34 to 8.81%. Under the most favorable
      conditions, the solid-phase extraction combined with HPLC-UV for the analysis of
      four drugs in plasma could eliminate interferences from endogenous components of
      the biological fluids and exhibited sufficient precision and accuracy. These
      results showed that the prepared Fe3 O4 @FPBA MNPs were qualified for efficiently
      enriching and determining the trace cis-diol substances from biological samples.

PMID- 25059978
TI  - Starvation-response may not involve Atg1-dependent autophagy induction in non
      unikont parasites.
AB  - Autophagy, the lysosome-mediated self-degradation process, is implicated in
      survival during starvation in yeast, Dictyostelium and animals. In these
      eukaryotic taxa (collectively called Unikonts), autophagy is induced primarily
      through the Atg1/ULK1 complex in response to nutrient depletion. Autophagy has
      also been well-studied in non-unikont parasites, such as Trypanosoma and
      Plasmodium, and found important in their life-cycle transitions. However, how
      autophagy is induced in non-unikonts remains largely unrevealed. Using a
      bioinformatics approach, we examined the presence of Atg1 and of its complex in
      the genomes of 40 non-unikonts. We found that these genomes do not encode typical
      Atg1 proteins: BLAST and HMMER queries matched only with the kinase domain of
      Atg1, while other segments responsible for regulation and protein-binding were
      missing. Non-unikonts also lacked other components of the Atg1-inducing complex.
      Orthologs of an alternative autophagy inducer, Atg6 were found only in the half
      of the species, indicating that the other half may possess other inducing
      mechanisms. As key autophagy genes have differential expression patterns during
      life-cycle, we raise the possibility that autophagy in these protists is induced
      mainly at the post-transcriptional level. Understanding Atg1-independent
      autophagy induction mechanisms in these parasites may lead to novel
      pharmacological interventions, not affecting human Atg1-dependent autophagy. 

PMID- 25059979
TI  - Health benefits of serious involvement in leisure activities among older Korean
      adults.
AB  - The existing literature suggests that serious engagement in leisure activities
      leads to happiness, life satisfaction, and successful aging among older adults.
      This qualitative study was used to examine the benefits of serious involvement in
      leisure activities among older Korean adults who were members of a sports club.
      Using an analytic data analysis, we identified three main themes associated with
      the benefits of serious engagement in leisure activities: 1) the experience of
      psychological benefits, 2) the creation of social support, and 3) the enhancement
      of physical health. These themes indicate that, through serious involvement in
      certain physical activities, participants gain various health benefits, which may
      contribute to successful aging. 

PMID- 25059980
TI  - When a clear strong voice was needed: A retrospective review of Watson's
      (1924/1930) behaviorism.
AB  - Despite the attention given John B. Watson during the century since he introduced
      behaviorism, there remain questions about what he really contributed. He is still
      appropriately criticized for his arrogant self-promotion and especially for his
      perceived emphasis on a simple S-R reflexology. However, we argue that the former
      was necessary at the time and that criticism of Watson on the second count only
      diverts attention from the genuine contributions that he did make. In support of
      these contentions we examine several aspects of his contributions that warrant
      clarification, namely, his promotion of applied comparative psychology, his views
      on the nature of mind, his originality, criticism from and respect afforded by
      contemporaries, his relation to recent interest in "the embodiment of mind," his
      treatment of thinking, and his appreciation of Freud's work. We organize our
      discussion around specific chapters of the two editions of Behaviorism, but in
      support of our arguments we include publications of Watson that are less well
      known. Those works develop some important points that are only briefly treated in
      both editions of Behaviorism.

PMID- 25059981
TI  - Apps to promote physical activity among adults: a review and content analysis.
AB  - BACKGROUND: In May 2013, the iTunes and Google Play stores contained 23,490 and
      17,756 smartphone applications (apps) categorized as Health and Fitness,
      respectively. The quality of these apps, in terms of applying established health
      behavior change techniques, remains unclear. METHODS: The study sample was
      identified through systematic searches in iTunes and Google Play. Search terms
      were based on Boolean logic and included AND combinations for physical activity,
      healthy lifestyle, exercise, fitness, coach, assistant, motivation, and support.
      Sixty-four apps were downloaded, reviewed, and rated based on the taxonomy of
      behavior change techniques used in the interventions. Mean and ranges were
      calculated for the number of observed behavior change techniques. Using
      nonparametric tests, we compared the number of techniques observed in free and
      paid apps and in iTunes and Google Play. RESULTS: On average, the reviewed apps
      included 5 behavior change techniques (range 2-8). Techniques such as self
      monitoring, providing feedback on performance, and goal-setting were used most
      frequently, whereas some techniques such as motivational interviewing, stress
      management, relapse prevention, self-talk, role models, and prompted barrier
      identification were not. No differences in the number of behavior change
      techniques between free and paid apps, or between the app stores were found.
      CONCLUSIONS: The present study demonstrated that apps promoting physical activity
      applied an average of 5 out of 23 possible behavior change techniques. This
      number was not different for paid and free apps or between app stores. The most
      frequently used behavior change techniques in apps were similar to those most
      frequently used in other types of physical activity promotion interventions.

PMID- 25059982
TI  - Effect of sitagliptin therapy on triglyceride-rich lipoprotein kinetics in
      patients with type 2 diabetes.
AB  - AIM: To investigate the effects of sitagliptin therapy on the kinetics of
      triglyceride-rich lipoprotein (TRL) apolipoprotein (apo)B-48, VLDL apoB-100, apoE
      and apoC-III in patients with type 2 diabetes. METHODS: Twenty-two subjects with
      type 2 diabetes were recruited in this double-blind crossover study, during which
      the subjects received sitagliptin (100 mg/day) or placebo for a 6-week period
      each. At the end of each phase of treatment, the in vivo kinetics of the
      different apolipoproteins were assessed using a primed-constant infusion of l
      [5,5,5-D3]leucine for 12 h, with the participants in a constantly fed state.
      RESULTS: Sitagliptin therapy significantly reduced fasting plasma triglyceride (
      15.4%, p = 0.03), apoB-48 (-16.3%, p = 0.03) and free fatty acid concentrations (
      9.5%, p = 0.04), as well as plasma HbA1c (placebo: 7.0% +/- 0.8 vs. sitagliptin:
      6.6% +/- 0.7, p < 0.0001) and plasma glucose levels (-13.5%, p = 0.001), without
      any significant effect on insulin levels. Kinetic results showed that treatment
      with sitagliptin significantly reduced the pool size of TRL apoB-48 by -20.8% (p
      = 0.03), paralleled by a reduction in the production rate of these particles (
      16.0%, p = 0.03). The VLDL apoB-100 pool size was also significantly decreased by
      sitagliptin therapy (-9.3%, p = 0.03), mainly because of a reduction in the
      hepatic secretion of these lipoproteins, although this difference did not reach
      statistical significance (-9.2%, p = 0.06). CONCLUSIONS: Treatment with
      sitagliptin for 6 weeks reduced triglyceride-rich apoB-containing lipoprotein
      levels by reducing the synthesis of these particles.

PMID- 25059983
TI  - Differentiation of human induced pluripotent stem cells into insulin-like cell
      clusters with miR-186 and miR-375 by using chemical transfection.
AB  - Diabetes mellitus is characterized by either the inability to produce insulin or
      insensitivity to insulin secreted by the body. Islet cell replacement is an
      effective approach for diabetes treatment; however, it is not sufficient for all
      the diabetic patients. MicroRNAs (miRNAs) are a class of small noncoding RNAs
      that play an important role in mediating a broad and expanding range of
      biological activities, such as pancreas development. The present study aimed to
      develop a protocol to efficiently differentiate human induced pluripotent stem
      (iPS) cells into islet-like cell clusters (ILCs) in vitro by using miR-186 and
      miR-375. The human iPS colonies were transfected with hsa-miR-186 and hsa-miR-375
      by using siPORTTM NeoFXTM Transfection Agent, and the differentiation was
      compared to controls. Total RNA was extracted 24 and 48 h after transfection. The
      gene expressions of insulin, NGN3, GLUT2, PAX4, PAX6, KIR6.2, NKX6.1, PDX1,
      Glucagon, and OCT4 were then evaluated through real-time qPCR. On the third day,
      the potency of the clusters was assessed in response to high glucose levels.
      Dithizone (DTZ) was used to identify the existence of the beta-cells. Besides,
      the presence of insulin and NGN3 proteins was investigated by
      immunocytochemistry. Morphological changes were observed on the first day after
      the chemical transfection, and cell clusters were formed on the third day. The
      expression of pancreatic specific transcription factors was increased on the
      first day and significantly increased on the second day. The ILCs were positive
      for insulin and NGN3 proteins in the immunocytochemistry. Besides, the clusters
      were stained with DTZ and secreted insulin in glucose challenge test.
      Overexpression of miR-186 and miR-375 can be an alternative strategy for
      producing ILCs from the iPS cells in a short time. This work provides a new
      approach by using patient-specific iPSCs for beta-cell replacement therapy in
      diabetic patients.

PMID- 25059984
TI  - High-level expression of a manganese superoxide dismutase (PoMn-SOD) from
      Pleurotus ostreatus in Pichia pastoris.
AB  - The full-length cDNA of Pleurotus ostreatus superoxide dismutase (PoMn-SOD) was
      cloned and successfully expressed by using the pPIC9K vector under the control of
      alcohol oxidase 1 promoter with a secretion signal peptide (alpha-factor) in
      Pichia pastoris. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and Western blotting demonstrated that recombinant PoMn-SOD, a 21.8 kDa
      protein, was secreted into the culture medium. Nondenaturing PAGE experiments
      confirmed that recombinant PoMn-SOD was secreted in a functionally active form
      and the expression system did not require any acid activation process. The
      factors affecting the expression level were optimized in shaking flask cultures.
      The maximum enzyme activity (156.9 U/mg) was observed under the following
      conditions: Initial medium pH was 6.0, induction time point was at the 6th day,
      and methanol concentration was 0.7 % (v/v). This was the first report on
      secretory expression of recombinant PoMn-SOD in P. pastoris, which might provide
      a reference for further practical applications.

PMID- 25059985
TI  - D-wave recording during the surgery of a 10-month-old child.
AB  - PURPOSE: The purpose of this study is to evaluate the possibility of d-wave
      recording in very young patients during spinal cord surgery. METHOD: A 10-month
      old patient was operated on cystic intramedullary pathology and myelon tethering
      at level cervical VI. to thoracal III. During the surgical detethering, we did d
      wave recording for experimental purposes. After transcranial electric
      stimulation, we tried to detect the responses with epidural d-wave electrodes
      proximally and distally from the pathology. RESULTS: We found that proximally
      from the pathology, we could detect reproducible d-waves. CONCLUSION: Though
      earlier papers reported that due to the immature condition of the myelon d-wave
      recording is not possible under the age of 21 months, we proved that even in very
      young patients, the possibility of d-wave recording should not be excluded.

PMID- 25059986
TI  - Intradural extra medullary hemangiopericytoma of dorsal spine.
AB  - PURPOSE: Spinal hemangiopericytoma is a rare neoplasm that behaves similar to
      intracranial hemangiopericytoma, with approximately 60 cases being reported in
      the literature of which only 10 are located in the intradural extramedullary
      (IDEM) location. METHODS: We report a rare case of recurrent IDEM
      hemangiopericytoma of dorsal spine in a 16-year-old boy treated with surgery and
      adjuvant radiotherapy. RESULTS: Patient is disease free at 5 years posttreatment
      with residual neurological deficit, but is able to carry out his activities of
      daily living. CONCLUSION: Gross total resection, if feasible, followed by
      radiotherapy is the initial treatment of choice as radiotherapy improves
      recurrence free survival as well as overall survival.

PMID- 25059987
TI  - Inhibition of adjuvant-induced arthritis by nasal administration of novel
      synthetic peptides from heat shock protein 65.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease
      mediated by T cells. The aim of the present study was to investigate the
      therapeutic efficacy of synthetic peptides (HP-R1, HP-R2 and HP-R3), derived from
      the sequence of 65-kD mycobacterial heat shock protein (HSP), in the treatment of
      RA using adjuvant-induced arthritis (AA) animal model. METHODS: AA was induced by
      a single intradermal injection Freund's complete adjuvant in male Lewis rats. At
      the first clinical sign of disease, rats were administered nasally by
      micropipette of peptides or phosphate buffer saline (PBS). Disease progression
      was monitored by measurement of body weight, arthritis score and paw swelling.
      The changes of histopathology were assessed by hematoxylin eosin staining. The
      serum levels of tumor necrosis factor (TNF) - alpha and interleukin (IL)-4 were
      measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The peptides
      efficiently inhibited the footpad swelling and arthritic symptoms in AA rats. The
      synthetic peptides displayed significantly less inflammatory cellular
      infiltration and synovium hyperplasia than model controls. This effect was
      associated with a suppression of pro-inflammatory cytokine TNF-alpha production
      and an increase of anti-inflammatory cytokine IL-4 production after peptides
      treatment. CONCLUSIONS: These results suggest that the synthetic peptides derived
      from HSP65 induce highly effective protection against AA, which is mediated in
      part by down-regulation of inflammatory cytokines, and support the view that the
      synthetic peptides is a potential therapy for RA that may help to diminish both
      joint inflammation and destruction.

PMID- 25059988
TI  - Near-infrared light responsive multi-compartmental hydrogel particles synthesized
      through droplets assembly induced by superhydrophobic surface.
AB  - Light-responsive hydrogel particles with multi-compartmental structure are useful
      for applications in microreactors, drug delivery and tissue engineering because
      of their remotely-triggerable releasing ability and combinational
      functionalities. The current methods of synthesizing multi-compartmental hydrogel
      particles typically involve multi-step interrupted gelation of polysaccharides or
      complicated microfluidic procedures with limited throughput. In this study, a two
      step sequential gelation process is developed to produce agarose/alginate double
      network multi-compartmental hydrogel particles using droplets assemblies induced
      by superhydrophobic surface as templates. The agarose/alginate double network
      multi-compartmental hydrogel particles can be formed with diverse hierarchical
      structures showing combinational functionalities. The synthesized hydrogel
      particles, when loaded with polypyrrole (PPy) nanoparticles that act as
      photothermal nanotransducers, are demonstrated to function as near-infrared (NIR)
      light triggerable and deformation-free hydrogel materials. Periodic NIR laser
      switching is applied to stimulate these hydrogel particles, and pulsatile release
      profiles are collected. Compared with massive reagents released from single
      compartmental hydrogel particles, more regulated release profiles of the multi
      compartmental hydrogel particles are observed. 

PMID- 25059989
TI  - Synthesis, structure, and reactivity of diazene adducts: isolation of iso-diazene
      stabilized as a borane adduct.
AB  - This work describes the synthesis and full characterization of a series of GaCl3
      and B(C6 F5 )3 adducts of diazenes R(1) ?N?N?R(2) (R(1) =R(2) =Me3 Si, Ph; R(1)
      =Me3 Si, R(2) =Ph). Trans-Ph?N?N?Ph forms a stable adduct with GaCl3 , whereas no
      adduct, but instead a frustrated Lewis acid-base pair is formed with B(C6 F5 )3 .
      The cis-Ph?N?N?Ph?B(C6 F5 )3 adduct could only be isolated when UV light was
      used, which triggers the isomerization from trans- to cis-Ph?N?N?Ph, which
      provides more space for the bulky borane. Treatment of trans-Ph?N?N?SiMe3 with
      GaCl3 led to the expected trans-Ph?N?N?SiMe3 ?GaCl3 adduct but the reaction with
      B(C6 F5 )3 triggered a 1,2-Me3 Si shift, which resulted in the formation of a
      highly labile iso-diazene, Me3 Si(Ph)N?N; stabilized as a B(C6 F5 )3 adduct.
      Trans-Me3 Si?N?N?SiMe3 forms a labile cis-Me3 Si?N?N?SiMe3 ?B(C6 F5 )3 adduct,
      which isomerizes to give the transient iso-diazene species (Me3 Si)2 N?N?B(C6 F5
      )3 upon heating. Both iso-diazene species insert easily into one B?C bond of B(C6
      F5 )3 to afford hydrazinoboranes. All new compounds were fully characterized by
      means of X-ray crystallography, vibrational spectroscopy, CHN analysis, and NMR
      spectroscopy. All compounds were further investigated by DFT and the bonding
      situation was assessed by natural bond orbital (NBO) analysis. 

PMID- 25059990
TI  - When the hidden features become evident: the usefulness of PMCT in a
      strangulation-related death.
AB  - Asphyxia related-death is a common incident in forensic practice, since they can
      be related to suicide, homicide and accident. The deep structures of the neck can
      be very difficult to reach using the traditional neck dissection when no certain
      information about potential injuries are obtained. Furthermore in this kind of
      deaths no specific signs or injuries can be found at the external and internal
      examination of the body (such as the slight, if any, displacement of a body
      structure following a infraction and fissures, as well as injuries involving
      lamellae of the thyroid cartilage, cricoid cartilage, trachea). In recent years a
      great contribute to the field of postmortem diagnostics (e.g. gunshot wounds,
      sharp and blunt forces, etc.) has been given by the introduction of the post
      mortem CT (PMCT); that is becoming a standard procedure performed before the
      traditional postmortem examination. In cases of asphyxia related-death (with
      special regards to homicidal strangulation) the PMCT with 3D documentation can be
      very helpful in revealing injuries on the small structures of the neck, that can
      be also masked by soft tissues and surrounding bleedings and provides a useful
      guide for the pathologist to choose the right dissecting technique and avoid
      artifacts or iatrogenic injury to delicate structures, such as hyoid bone or
      thyroid cartilage. The case of a homicide by ligature strangulation using two
      items (electric wire and cotton bed sheet) is presented, in which the PMCT was
      performed before the autopsy, showing helpful features concerning the mechanism
      of death. 

PMID- 25059991
TI  - HPV prevalence and type distribution in women with normal or abnormal Pap smear
      in Bulgaria.
AB  - Human papillomavirus (HPV) is a well-known pathogen for lower genital tract
      neoplasias, yet little is known regarding HPV prevalence in Bulgaria. The aim of
      this study was to investigate the prevalence of HPV DNA and to determine HPV
      types distribution among women with normal and abnormal cytology. Cervical smears
      with different cytological diagnoses were collected from 355 Bulgarian patients.
      The cohort of patients selected is the biggest ever studied in this country.
      Using the Roche Linear Array HPV Genotyping Test, papillomavirus DNA was found in
      217 out of the 355 samples, 164 of which had only one and 53 had more than one
      HPV type. The distribution of the viruses tested in 355 samples was as follows:
      (i) the most common type was HPV 16, which was found in 61 samples; (ii) the next
      most frequent HPV type was HPV 33, found in 14 of the samples. A high prevalence
      of HPV infection was observed in this study. As HPV infection has a high
      correlation with cervical cancer, this study emphasizes the need for both primary
      prevention of cervical cancer with HPV vaccines as well as secondary prevention
      with screening. Currently, two HPV vaccines are included in the National
      immunization schedule in Bulgaria. Thus, new clinical studies will benefit from
      patient stratification by the presence or absence of HPV, and by designing
      separate clinical trials specifically for HPV associated cancers.

PMID- 25059992
TI  - Josephson parametric phase-locked oscillator and its application to dispersive
      readout of superconducting qubits.
AB  - The parametric phase-locked oscillator (PPLO) is a class of frequency-conversion
      device, originally based on a nonlinear element such as a ferrite ring, that
      served as a fundamental logic element for digital computers more than 50 years
      ago. Although it has long since been overtaken by the transistor, there have been
      numerous efforts more recently to realize PPLOs in different physical systems
      such as optical photons, trapped atoms, and electromechanical resonators. This
      renewed interest is based not only on the fundamental physics of nonlinear
      systems, but also on the realization of new, high-performance computing devices
      with unprecedented capabilities. Here we realize a PPLO with Josephson-junction
      circuitry and operate it as a sensitive phase detector. Using a PPLO, we
      demonstrate the demodulation of a weak binary phase-shift keying microwave signal
      of the order of a femtowatt. We apply PPLO to dispersive readout of a
      superconducting qubit, and achieved high-fidelity, single-shot and non
      destructive readout with Rabi-oscillation contrast exceeding 90%. 

PMID- 25059993
TI  - Gel-to-fluid phase transformations in solid-supported phospholipid bilayers
      assembled by the Langmuir-Blodgett technique: effect of the Langmuir monolayer
      phase state and molecular density.
AB  - Planar-supported phospholipid bilayers are increasingly used as synthetic
      membranes for scientific and practical applications. The thermotropic phase
      properties of supported bilayers are important for recreating biologically
      relevant situations. Unlike free-standing lipid membranes that undergo one gel-to
      fluid or main phase transition, mica-supported single bilayers have been found to
      undergo two separate leaflet transitions. Although the distinctive nature of the
      main transition in mica-supported bilayers has been attributed to different
      effects, determining their relevance has been problematic because vesicle fusion,
      the technique most widely used to prepare solid-supported bilayer membranes, does
      not allow one to readily control the lipid surface coverage and molecular
      density. To circumvent the limitations of the vesicle fusion method and
      systematically investigate the effects on the individual leaflet transitions of
      the lipid phase state and molecular density before deposition on the substrate,
      mica-supported single bilayers of 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were prepared using
      the Langmuir-Blodgett technique. The gel-to-fluid transitions of the bilayer
      leaflets were tracked by controlled-temperature atomic force microscopy to
      determine the relative fractions of the gel and fluid phases as a function of
      temperature. The fraction of solid versus temperature data was fit to the van't
      Hoff equation to determine the leaflet melting temperatures and transition
      enthalpies. The phase state and molecular density of the Langmuir monolayer
      precursor at the transfer pressure of 35 mN m(-1) was found to have a greater
      effect on the main transition temperature and width of the distal (upper) leaflet
      than that of the proximal (lower) one. The contributions of substrate-mediated
      condensation, asymmetric lipid densities, and surface area available for thermal
      expansion of the bilayer are addressed. This work demonstrates the potential of
      the Langmuir-Blodgett technique as a tool for identifying and manipulating the
      factors that govern the phase transition properties of surface-confined lipid
      bilayers. 

PMID- 25059994
TI  - Anaesthetic management of cytoreductive surgery followed by hyperthermic
      intrathoracic chemotherapy perfusion.
AB  - BACKGROUND: Macroscopic cytoreductive surgery and hyperthermic intrathoracic
      chemotherapy perfusion (HITHOC) is a new multimodal approach for selected
      patients with primary and secondary pleural tumors, which may provide the patient
      with better local tumor control and increased overall survival rate. METHODS: We
      present a single-center study including 20 patients undergoing cytoreductive
      surgery and HITHOC between September 2008 and April 2013 at the University
      Medical Center Regensburg, Germany. Objective of the study was to describe the
      perioperative, anaesthetic management with special respect to pain and
      complication management. RESULTS: Anaesthesia during this procedure is
      characterized by increased intrathoracic airway and central venous pressure,
      hemodynamic alterations and the risk of systemic hypo- and hyperthermia. Securing
      an adequate intravascular volume is one of the primary goals to prevent decreased
      cardiac output as well as pulmonary edema. Transfusion of packed red blood cells
      (PRBC) was necessary in seven of 20 (35%) patients. Only two patients (10%)
      showed an impairment of coagulation in postoperative laboratory analysis.
      Perioperative forced diuresis is recommended to prevent postoperative renal
      insufficiency. Supplementary thoracic epidural analgesia in 13 patients (65%)
      showed a significant reduction of post-operative pain compared with peroral
      administration of opioid and non-opioid analgesics. CONCLUSION: This article
      summarizes important experiences of the anaesthesiological and intensive care
      management in patients undergoing HITHOC.

PMID- 25059995
TI  - [Quality of vision studied by comparative measurement of light scattering].
AB  - PURPOSE: To assess quality of vision by measuring ocular light scattering with
      two platforms and comparing them to traditional tests, in healthy subjects and
      cataract patients. PATIENTS AND METHODS: One hundred and sixty-eight eyes divided
      in two groups were examined by the same clinician in a prospective study (group
      1, healthy controls, with a mean age of 31.22 [+/- 6.76]; and group 2, patients
      presenting with cataract, with a mean age of 60.36 [+/- 10.27]). Patients with
      ocular surface disease were excluded from this study. Each group responded to the
      VF-14 questionnaire, underwent an examination with lens opacities assessed by
      LOCS III and a measurement of ocular light scattering with two platforms: the
      OQAS (Visiometrics((c))) and the C-Quant (Oculus((c))). We analyzed correlations
      between indices of light scattering with the two platforms (respectively OSI and
      log(s)) and traditional quality of vision tests (VF-14 questionnaire and LOCS
      III). RESULTS: Strong correlations were found between the OSI and LOCS III.
      Moderate correlations were found between the OSI and the VF-14 questionnaire, as
      well as between log(s), VF-14 questionnaire and LOCS III. CONCLUSION: Indices of
      light scattering seems to be valid tools to assess quality of vision, thus
      lending themselves to routine testing of visual function.

PMID- 25059996
TI  - Isolation and characterization of eight microsatellite loci in the brook lamprey
      Lampetra planeri (Petromyzontiformes) using 454 sequence data.
AB  - Eight polymorphic microsatellite loci were developed for the brook lamprey
      Lampetra planeri through 454 sequencing and their usefulness was tested in 45
      individuals of both L. planeri and the river lamprey Lampetra fluviatilis. The
      number of alleles per loci ranged between two and five; the Italian and Irish
      populations had a mean expected heterozygosity of 0.388 and 0.424 and a mean
      observed heterozygosity of 0.418 and 0.411, respectively. 

PMID- 25059997
TI  - Mites from Cerrado fragments and adjacent soybean crops: does the native
      vegetation help or harm the plantation?
AB  - Aiming to recognize the distribution patterns of the mite fauna in soybean crops
      and to determine the existence of similarity in the composition of species
      between Cerrado fragments and these plantations, samplings were carried out in 10
      areas located in Brazilian Mid-Western and Southeastern regions. Each area was
      comprised of one fragment of Cerrado sensu stricto and one adjacent soybean crop
      plantation, with simultaneous samplings carried out on both of them. From the
      total sampled species, 111 were recorded in the Cerrado and 25 in soybean crops.
      About 68 % were common in both environments and only eight were exclusively found
      in soybean. All the species of Phytoseiidae recorded in soybean were also found
      in the Cerrado. The tetranychid mite Mononychellus planki (McGregor) was the most
      abundant species (96.3 % of the total individuals) and the only one recorded in
      every sampled crop. The main occurrence of M. planki was verified in soybean
      crops using the transgenic cultivar ANTA 82. In general terms, it has been
      observed that Cerrado fragments do not shelter pest species that may attack
      soybean and can contribute to the increase of possible predator species in this
      agroecosystem. 

PMID- 25059998
TI  - A new robot for flexible ureteroscopy: development and early clinical results
      (IDEAL stage 1-2b).
AB  - BACKGROUND: An improved armamentarium has had a significant impact on the
      emerging role of flexible ureteroscopy (FURS) for the management of
      nephrolithiasis; however, FURS still represents a challenging technique.
      OBJECTIVE: To examine a robotic device designed for FURS for its impact on
      ergonomics and outcome of the procedure based on the IDEAL (idea, development,
      evaluation, assessment, long-term study) framework. DESIGN, SETTING, AND
      PARTICIPANTS: Roboflex Avicenna consists of a surgeon's console and a manipulator
      for the flexible ureterorenoscope. Following experimental evaluation of the
      prototype (IDEAL stage 1) and receipt of ethical approval, seven surgeons treated
      81 patients (mean age: 42 yr [range: 6-68]) with renal calculi (mean volume:
      1296+/-544 mm(3) [range: 432-3100 mm3]) in an observational study (IDEAL stage
      2). SURGICAL PROCEDURE: Robotic FURS was performed with the Roboflex Avicenna
      robotic device. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Numerical data
      were analysed with the Mann-Whitney test, and categorical variables were analysed
      using the chi-square test or Fisher exact test. P values <0.05 were considered
      statistically significant. RESULTS AND LIMITATIONS: Mean robot docking time was
      59.6+/-45 s. Mean operative time was 74min (range: 40-182). Mean fragmentation
      speed was 29.1+/-6.1 mm3/min. Ergonomics based on a validated questionnaire
      showed significant advantage for robotic FURS (total score: 5.6 vs 31.3; p<0.01).
      A 10/12F-access sheath was used in 72 patients. Two cases required secondary
      FURS, one because of malfunction of the flexible digital ureteroscope and another
      because of larger residual fragments. In the remaining 79 cases, complete stone
      disintegration was accomplished. CONCLUSIONS: Roboflex Avicenna provides a
      suitable and safe platform for robotic FURS with significant improvement of
      ergonomics. Future studies should evaluate its impact on the clinical outcome of
      FURS. PATIENT SUMMARY: Robotic flexible ureteroscopy (FURS) was performed with
      the Roboflex Avicenna robotic device. Results showed that Roboflex Avicenna
      provides a suitable and safe platform for robotic FURS with significant
      improvement of ergonomics.

PMID- 25059999
TI  - High frequency of intracranial arterial stenosis and cannabis use in ischaemic
      stroke in the young.
AB  - BACKGROUND: Leading aetiologies of ischaemic stroke in young adults are cervico
      cerebral arterial dissections and cardio-embolism, but the causes remain
      undetermined in a considerable proportion of cases. In a few reports,
      intracranial arterial stenosis has been suggested to be a potential cause of
      ischaemic stroke in young adults. The aim of our work was to evaluate the
      frequency, characteristics and risk factors of intracranial arterial stenosis in
      a prospective series of young ischaemic stroke patients. METHODS: The study was
      based on a prospective consecutive hospital-based series of 159 patients aged 18
      45 years who were admitted to our unit for an acute ischaemic stroke from October
      2005 to December 2010. A structured questionnaire was used in order to assess
      common vascular risk factors such as hypertension, diabetes,
      hypercholesterolemia, use of tobacco, alcohol and illicit drugs, migraine, and,
      in women, oral contraceptive use. A systematic screening was performed, including
      the following: brain magnetic resonance imaging or, if not feasible, brain
      computed tomography scan, carotid and vertebral Duplex scanning and trans-cranial
      Doppler sonography, 3D time-of-flight magnetic resonance cerebral angiography or
      cerebral computed tomography angiography. Long-duration electrocardiography,
      trans-thoracic and trans-oesophageal echocardiography were performed and
      laboratory blood investigations were extensive. Urine samples were screened for
      cannabinoids, cocaine, amphetamine and methylene-dioxy-methamphetamine. When this
      initial work-up was inconclusive, trans-femoral intra-arterial selective digital
      subtraction angiography with reconstructed 3D images was performed. RESULTS: In
      this series, 49 patients (31%) had intracranial arterial stenosis. Other defined
      causes were found in 91 patients (57%), including cardio-embolism in 32 (20%),
      cervical dissection in 23 (14%), extracranial atherosclerosis in 7 (4%),
      haematological disorders in 7 (4%), small vessel disease in 1, and isolated
      patent foramen ovale in 21 (13%); in 19 patients (12%), ischaemic stroke was
      related to an undetermined aetiology. Comparing risk factors between patients
      with intracranial arterial stenosis and those with other definite causes showed
      that there were only two significant differences: a lower age and a higher
      frequency of vasoactive substances (especially cannabis) in patients with
      intracranial arterial stenosis. All intracranial arterial stenosis in patients
      who used vasoactive substances were located in several intracranial vessels.
      CONCLUSIONS: Intracranial arterial stenosis may be an important mechanism of
      stroke in young patients and it should be systematically investigated using
      vascular imaging. Strong questioning about illicit drug consumption (including
      cannabis) or vasoactive medication use should also be performed. It should be
      emphasized for health prevention in young adults that cannabis use might be
      associated with critical consequences such as stroke.

PMID- 25060000
TI  - Evolutionary multi-objective optimization based comparison of multi-column
      chromatographic separation processes for a ternary separation.
AB  - Performance characteristics of two advanced multi-column chromatographic
      separation processes with discontinuous feed, Multi-Column Recycling
      Chromatogrphy (MCRC) and Japan Organo (JO), were investigated for a ternary
      separation using multi-objective optimization with an evolutionary algorithm.
      Conventional batch process was used as a reference. Fractionation of a
      concentrated acid hydrolysate of wood biomass into sulfuric acid, monosaccharide,
      and acetic acid fractions was used as a model system. Comparison of the
      separation processes was based on selected performance parameters in their
      optimized states. Flow rates and step durations were taken as decision variables
      whereas the column configuration and dimensions were fixed. The MCRC process was
      found to be considerably more efficient than the other processes with respect to
      eluent consumption. The batch process gave the highest productivity and the JO
      process the lowest. Both of the multi-column processes gave significantly higher
      monosaccharide yield than the batch process. When eluent consumption and
      monosaccharide yield are taken into account together with productivity, the MCRC
      process was found to be the most efficient in the studied case. 

PMID- 25060001
TI  - Is starting hemodialysis on a twice-weekly regimen a valid option?

PMID- 25060002
TI  - Breaking down the vitamin D-GFR relationship.

PMID- 25060003
TI  - Revisiting frontiers of tolerability and efficacy in renal replacement therapy.

PMID- 25060004
TI  - In reply to 'A perspective from the Baltics regarding the Canadian Society of
      Nephrology commentary on the KDIGO Glomerulonephritis Guideline'.

PMID- 25060005
TI  - A perspective from the Baltics regarding the Canadian Society of Nephrology
      commentary on the KDIGO Glomerulonephritis Guideline.

PMID- 25060007
TI  - Quiz page August 2014: pruritus in a dialysis patient. Mycosis fungoides
      (folliculotropic variant) in a dialysis patient, with rare presentation of
      persistent generalized pruritus with characteristics of uremic pruritus without
      skin lesions.

PMID- 25060008
TI  - Oxidative rearrangements during fungal biosynthesis.
AB  - Oxidative rearrangements are key reactions during the biosyntheses of many
      secondary metabolites in fungi. This review highlights the most important
      examples of these reactions and aims to draw together key mechanistic themes to
      allow a better understanding and future exploitation of this key class of fungal
      catalysts.

PMID- 25060009
TI  - Descending necrotizing mediastinitis with diffuse ST elevation mimicking
      pericarditis: a case report.
AB  - BACKGROUND: Descending necrotizing mediastinitis (DNM) is a potentially fatal
      disease that requires aggressive treatment, including mediastinal exploration.
      The inflammation associated with DNM may involve the heart, which produces acute
      changes in the electrocardiogram (ECG). As a result, the ECG may mimic
      pericarditis, causing some diagnostic confusion. OBJECTIVES: The objectives of
      this case report are to describe a case of DNM presenting
      electrocardiographically with pericarditis, and to discuss how to differentiate
      between benign viral pericarditis and DNM, and the management of these two
      diseases. CASE REPORT: We present the case of a previously healthy 50-year-old
      man who presented to the Emergency Department for chest pain and presumed
      pericarditis. The patient presented with ST elevation on multiple leads on ECG,
      tenderness in the neck, widened mediastinum on the chest radiograph, and
      nonspecific laboratory test results. Echocardiography revealed normal ventricle
      function and the presence of mild pericardial effusion. The emergency physician
      performed contrast-enhanced neck computed tomography (CT) to rule out deep-neck
      infection. The CT scan showed marginal rim-enhancing abscesses in the
      retropharyngeal, bilateral submandibular, and anterior visceral spaces with
      extension into the thoracic cavity. Contrast-enhanced chest CT was performed
      consecutively. The final diagnosis was deep-neck infection with DNM. The patient
      underwent mediastinoscopy-assisted drainage and neck fasciotomy twice and
      received 7 weeks of therapy with intravenous meropenem. CONCLUSION: The present
      case highlights the importance of considering a mediastinal cause for acute ECG
      changes.

PMID- 25060010
TI  - Confronting blunt cardiac trauma.

PMID- 25060011
TI  - QTc prolongation as a useful prognostic factor in acute paraquat poisoning.
AB  - BACKGROUND: Acute paraquat poisoning has a high mortality rate. Several
      prognostic factors have been proposed to predict the mortality risk of paraquat
      poisoned patients. However, these prognostic factors are complex and some require
      a laboratory. Corrected QT (QTc) has been used as a prognostic factor in several
      clinical conditions, such as acute organophosphate poisoning. In addition, the
      measurement can be obtained in a reasonable amount of time. STUDY OBJECTIVES:
      This study's objective was to investigate whether QTc can predict mortality in
      paraquat-poisoned patients. METHODS: This was a retrospective study. Potential
      prognostic factors such as QTc, vital signs at admission, and certain
      biochemistry variables were analyzed with Cox regression analyses for their
      ability to predict a patient's survival from paraquat poisoning. RESULTS: Sixty
      acute paraquat-poisoned patients were admitted to the emergency department during
      the study period. The QTc of the survival group ranged from 0.35 to 0.48 s,
      whereas the nonsurvivor group ranged from 0.32 to 0.63 s. The nonsurvivor group
      contained a higher percentage of patients with QTc prolongation (>=0.45 s)
      compared with the survivor group (p = 0.04). The hazard ratio of QTc prolongation
      for a patient's death was found to be 2.47 (95% confidence interval [CI] 1.68
      5.67) in patients with a lower potassium level (<3.2 mEq/L) and 3.71 (95% CI 1.53
      8.97) in patients with a higher potassium level (>=3.2 mEq/L). In addition,
      hyperdynamic circulation was observed upon admission of these poisoned patients.
      CONCLUSION: QTc prolongation is a useful prognostic factor for predicting death
      in acute paraquat-poisoned patients. Cardiovascular collapse may occur in some
      paraquat-poisoned patients. Physicians can use QTc as an indicator of a patient's
      severity of poisoning and mortality risk.

PMID- 25060012
TI  - Ingested foreign body associated with bulimia nervosa.

PMID- 25060013
TI  - Comparative outcomes after unprotected left main stem percutaneous coronary
      intervention: a national linked cohort study of 5,065 acute and elective cases
      from the BCIS Registry (British Cardiovascular Intervention Society).
AB  - OBJECTIVES: The goal of this study was to report outcomes from percutaneous
      coronary intervention (PCI) to an unprotected left main stem (UPLMS) stenosis
      according to presenting syndrome, including ST-segment elevation myocardial
      infarction (STEMI), non-ST-segment elevation acute coronary syndrome (NSTEACS),
      and chronic stable angina (CSA). BACKGROUND: There are no published whole-country
      data concerning patient outcomes following PCI to UPLMS. METHODS: This study is a
      prospective national cohort study using data from the British Cardiovascular
      Intervention Society (BCIS) registry from January 1, 2005, through December 31,
      2010. RESULTS: Of 5,065 patients having PCI to an UPLMS, 784 (15.5%) presented
      with STEMI, 2,381 (47.0%) with NSTEACS, and 1,900 (37.5%) with CSA. Crude 30-day
      and 1-year mortality rates were STEMI: 28.3% and 37.6%, NSTEACS: 8.9% and 19.5%,
      and CSA: 1.4% and 7.0%, respectively. Unadjusted in-hospital major adverse
      cardiovascular and cerebrovascular event rates were STEMI: 26.6%, NSTEACS: 6.6%,
      and CSA: 3.3%. Risk of 30-day mortality was much greater for STEMI and NSTEACS
      patients than CSA (STEMI adjusted odds ratio [aOR]: 29.45, 95% confidence
      interval [CI]: 19.37 to 44.80, NSTEACS aOR: 6.45, 95% CI: 4.27 to 9.76). More
      than 40% of patients presenting with STEMI had cardiogenic shock, in whom
      mortality was higher than in STEMI cases without shock (30 days: 52.0% vs. 11.7%,
      1 year: 61.1% vs. 20.9%). Radial access, compared with the femoral approach, was
      associated with a lower risk of 30-day mortality (STEMI aOR: 0.37, 95% CI: 0.21
      to 0.62; NSTEACS aOR: 0.66, 95% CI: 0.45 to 0.97). CONCLUSIONS: More than one
      half of the patients who received UPLMS PCI were acute where outcomes were much
      worse than elective cases. Cardiogenic shock is common in STEMI patients, of whom
      more than one-half die at 30 days. The radial approach was associated with
      reduced early mortality in acute cases.

PMID- 25060014
TI  - How to optimize left main percutaneous coronary intervention.

PMID- 25060015
TI  - Impact of delay to reperfusion on reperfusion success, infarct size, and clinical
      outcomes in patients with ST-segment elevation myocardial infarction: the INFUSE
      AMI Trial (INFUSE-Anterior Myocardial Infarction).
AB  - OBJECTIVES: Our aim was to study the impact of delay from symptom onset to first
      coronary device on infarct size and clinical outcomes at 30 days and 1 year in
      patients with ST-segment elevation myocardial infarction (STEMI) treated with
      primary percutaneous coronary intervention. BACKGROUND: Longer delay from symptom
      onset to reperfusion has been linked to increased mortality and worse clinical
      outcome. The mechanisms underpinning this association are not entirely clear.
      METHODS: The INFUSE-AMI trial (INFUSE-Anterior Myocardial Infarction) randomized
      patients with anterior STEMI undergoing primary percutaneous coronary
      intervention with bivalirudin anticoagulation within 5 h of symptom onset to
      intralesion (IL) bolus abciximab versus no abciximab and to thrombus aspiration
      versus no aspiration. The primary endpoint was contrast magnetic resonance
      infarct size (IS) (percentage of left ventricular mass) at 30 days. Time to
      reperfusion was classified as <3 versus >=3 h. RESULTS: There were 280 patients
      (62%) with <3-h delay and 170 patients (38%) with >=3-h delay. Patients with
      longer delay were significantly older, more often women, and diabetic. Earlier
      reperfusion was not associated with higher rates of final Thrombolysis In
      Myocardial Infarction flow grade 3 or myocardial blush grade 2/3, but was an
      independent predictor of smaller IS (p = 0.02 by multivariable linear
      regression). Mortality at 1 year was reduced in patients with shorter delay to
      reperfusion (4.0% vs. 9.2%, p = 0.02). CONCLUSIONS: In patients with large
      anterior myocardial infarction undergoing relatively early reperfusion, longer
      delays to reperfusion were associated with larger IS and 1-year mortality, but
      not with reduced reperfusion success. (The INFUSE - Anterior Myocardial
      Infarction [AMI] Study; NCT00976521).

PMID- 25060016
TI  - ABSORB biodegradable stents versus second-generation metal stents: a comparison
      study of 100 complex lesions treated under OCT guidance.
AB  - OBJECTIVES: The aim of this study was to compare the acute performance of the
      PLLA ABSORB bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara,
      California) with second-generation metal drug-eluting stents (DES) in complex
      coronary artery lesions. BACKGROUND: Thick polymer-based BVS have different
      mechanical properties than thin second-generation DES. Data on the acute
      performance of BVS are limited to simple coronary lesions treated in trials with
      strict inclusion criteria. METHODS: Fifty complex coronary lesions (all type
      American College of Cardiology/American Heart Association B2-C) treated with a
      BVS undergoing a final optical coherence tomography (OCT) examination were
      compared with an equal number of matched lesions treated with second-generation
      DES. The following stent performance indexes were assessed with OCT: mean and
      minimal area, residual area stenosis (RAS), incomplete strut apposition (ISA),
      tissue prolapse, eccentricity index, symmetry index, strut fracture, and edge
      dissection. RESULTS: One hundred lesions from 73 patients were analyzed. A higher
      balloon diameter/reference vessel diameter ratio was used for predilation in the
      BVS group (p < 0.01). Most of the BVS and DES were post-dilated with short
      noncompliant (NC) balloons of similar diameter. OCT showed in the BVS group a
      higher tissue prolapse area (p = 0.08) and greater incidence of ISA at the
      proximal edge (p = 0.04) with no difference in the overall ISA. The RAS was 20.2%
      in the BVS group and 21.7% in the DES group (p = 0.32). There was no difference
      in the eccentricity index. The minimal and mean lumen areas were similar in the 2
      groups. Two cases of strut fractures occurred after the BVS, whereas none was
      observed in the DES. CONCLUSIONS: Based on OCT, the BVS showed similar post
      procedure area stenosis, minimal lumen area, and eccentricity index as second
      generation DES. The different approach for lesion preparation and routine use of
      OCT guidance during BVS expansion may have contributed to these results.

PMID- 25060017
TI  - Direct drug-eluting stenting to reduce stent restenosis: a randomized comparison
      of direct stent implantation to conventional stenting with pre-dilation or
      provisional stenting in elective PCI patients.
AB  - OBJECTIVES: The aim was to investigate whether a strategy of direct drug-eluting
      stent (DES) implantation without pre-dilation is associated with a reduced
      incidence of restenosis compared with CS with pre-dilation or provisional
      stenting (PS). BACKGROUND: Previous studies were performed comparing direct
      stenting (DS) with conventional stenting (CS) after pre-dilation; however, none
      of these in the DES era. Therefore, the STRESSED (direct Stenting To reduce
      REStenosis in Stent Era with Drug elution) study was designed and carried out.
      METHODS: A total of 600 patients with angina pectoris or recent myocardial
      infarction were randomized to a DS, CS, or PS strategy. The primary endpoint was
      the mean minimal lumen diameter at 9-month follow-up angiography. Secondary
      endpoints were clinical procedural success defined as angiographic success
      without in-hospital major adverse cardiac events (MACE), and MACE at 9-month and
      2-year follow-up. RESULTS: Stent implantation in the DS group was 98%, 99% in the
      CS group, and 77% in the PS group. Percutaneous coronary intervention success was
      99% in all groups. The minimal lumen diameter at 9-month follow-up was 2.12 +/-
      0.58 mm (DS), 2.17 +/- 0.67 mm (CS), and 1.99 +/- 0.69 mm (PS), p = 0.556 for
      comparison of DS with CS, p = 0.073 for comparison of DS with PS. The absolute
      difference was -0.05 (DS to CS), 95% confidence interval: -0.19 to -0.09, p =
      0.48 and 0.13 (DS to PS), confidence interval: -0.02 to -0.27, p = 0.087.
      Restenosis was found in 3.4% (DS), 6.7% (CS), and 11.5% (PS), p = 0.025. At 9
      month and 2-year follow-up, MACE occurred in 6.8% and 11.5% (DS), 4.6% and 10.3%
      (CS), and 7.6% and 13.8% (PS) (p = 0.439 and 0.536), respectively. CONCLUSIONS:
      Direct DES implantation compared with conventional DES implantation did not
      reduce restenosis. Provisional stenting, however, was associated with a higher
      rate of restenosis. This did not translate into a difference in the rate of MACE.
      (STRESSED study: direct Stenting To reduce REStenosis in Stent Era with Drug
      elution; ISRCTN41213536).

PMID- 25060018
TI  - Should every drug-eluting stent be deployed directly?

PMID- 25060019
TI  - Native coronary artery patency after coronary artery bypass surgery.
AB  - OBJECTIVES: The aim of the study was to determine native coronary artery patency
      1 year after coronary artery bypass grafting and to identify clinical and
      angiographic predictors for the development of a chronic total occlusion (CTO).
      BACKGROUND: In contrast to the large body of information regarding graft patency,
      data regarding atherosclerosis progression and vessel patency in surgically
      bypassed native coronary arteries are less clear. METHODS: Of the 440 patients
      who underwent 1-year follow-up angiography as part of the multicenter RAPS
      (Radial Artery Patency Study), included in our study were 388 patients (88%) for
      whom angiograms were available for review. Angiograms were reviewed for native
      coronary artery patency in an independent blinded manner. RESULTS: On the pre
      operative angiogram, CTO of at least 1 native coronary vessel was demonstrated in
      240 patients (61.9%) having 305 occluded vessels. At 1 year after coronary artery
      bypass grafting, at least 1 new native coronary artery CTO occurred in 169
      patients (43.6%). In 7.5% of patients, the native artery and the graft supplying
      that territory were both occluded. A new CTO was almost 5 times more likely to
      occur in coronary vessels with a pre-operative proximal stenosis >90% compared
      with vessels with proximal stenosis <90% (45.5% vs. 9.5%, respectively, p <
      0.001). Patients with a new CTO had significantly more baseline Canadian
      Cardiovascular Society class 4 angina compared with patients without a new CTO. A
      new CTO was less likely to occur in the left anterior descending artery (18.4%),
      supplied by the left internal thoracic artery. When comparing radial artery and
      saphenous vein grafts, neither the type of graft nor graft patency had any
      association with native coronary artery occlusion. CONCLUSIONS: CTO of surgically
      bypassed coronary arteries 1 year after coronary artery bypass grafting is
      extremely common.

PMID- 25060020
TI  - Fractional flow reserve calculation from 3-dimensional quantitative coronary
      angiography and TIMI frame count: a fast computer model to quantify the
      functional significance of moderately obstructed coronary arteries.
AB  - OBJECTIVES: This study sought to present a novel computer model for fast
      computation of myocardial fractional flow reserve (FFR) and to evaluate it in
      patients with intermediate coronary stenoses. BACKGROUND: FFR is an indispensable
      tool to identify individual coronary stenoses causing ischemia. Calculation of
      FFR from x-ray angiographic data may increase the utility of FFR assessment.
      METHODS: Consecutive patients with intermediate coronary stenoses undergoing
      pressure wire-based FFR measurements were analyzed by a core laboratory. Three
      dimensional quantitative coronary angiography (QCA) was performed and the mean
      volumetric flow rate at hyperemia was calculated using TIMI (Thrombolysis In
      Myocardial Infarction) frame count combined with 3-dimensional QCA. Computational
      fluid dynamics was applied subsequently with a novel strategy for the computation
      of FFR. Diagnostic performance of the computed FFR (FFRQCA) was assessed using
      wire-based FFR as reference standard. RESULTS: Computation of FFRQCA was
      performed on 77 vessels in 68 patients. Average diameter stenosis was 46.6 +/-
      7.3%. FFRQCA correlated well with FFR (r = 0.81, p < 0.001), with a mean
      difference of 0.00 +/- 0.06 (p = 0.541). Applying the FFR cutoff value of <=0.8
      to FFRQCA resulted in 18 true positives, 50 true negatives, 4 false positives,
      and 5 false negatives. The area under the receiver-operating characteristic curve
      was 0.93 for FFRQCA, 0.73 for minimum lumen area, and 0.65 for percent diameter
      stenosis. CONCLUSIONS: Computation of FFRQCA is a novel method that allows the
      assessment of the functional significance of intermediate stenosis. It may emerge
      as a safe, efficient, and cost-reducing tool for evaluation of coronary stenosis
      severity during diagnostic angiography.

PMID- 25060021
TI  - Fractional flow reserve from 3-dimensional quantitative coronary angiography:
      fresh light through an old window.

PMID- 25060022
TI  - Outcomes with post-dilation following transcatheter aortic valve replacement: the
      PARTNER I trial (placement of aortic transcatheter valve).
AB  - OBJECTIVES: This study sought to characterize the patients receiving post
      implantation balloon dilation (PD) following transcatheter aortic valve
      replacement (TAVR) and evaluate procedural outcomes in the PARTNER (Placement of
      Aortic Transcatheter Valve) I trial. BACKGROUND: Following TAVR, PD has been used
      to treat paravalvular regurgitation. METHODS: The PARTNER I trial cohort A (n =
      304) and cohort B (n = 194) patients randomized to TAVR and the nonrandomized
      continued access TAVR (n = 1,637) patients were included in the analysis. PD was
      performed at the discretion of the operator. Clinical events and
      echocardiographic variables were collected prospectively out to 1 year. RESULTS:
      The overall incidence of PD was 12.4%. PD patients had significantly less
      prosthesis-patient mismatch (p < 0.001) and larger effective orifice areas (p <
      0.001) throughout the follow-up period. There were significantly more subacute
      strokes (occurring <7 days: 4.9% vs. 2.6%; p = 0.04) in PD patients but no
      difference in late stroke, either at 7 to 30 days (0.0% vs. 0.8%; p = 0.16) or
      >30 days (1.9 vs. 1.7%; p = 0.75). Although there was no significant increase in
      early mortality with PD, at 1 year, there was a trend for higher all-cause
      mortality (p = 0.054) and a significant difference in death or stroke (p = 0.04).
      When the subgroup of patients with none/trace paravalvular regurgitation were
      evaluated, there was no significant association of PD with mortality (p = 0.61)
      and death or stroke (p = 0.96). Multivariable analysis failed to show a
      relationship between PD and mortality. CONCLUSIONS: PD is associated with reduced
      rates of moderate or severe prosthesis-patient mismatch with no evidence for
      short-term structural deterioration of the balloon-expandable transcatheter
      valve. Although PD is associated with a greater incidence of early stroke, there
      is no significant association between PD and stroke beyond 7 days. Multivariable
      analysis shows no significant association between PD and mortality.

PMID- 25060023
TI  - Balloon post-dilation after transcatheter aortic valve replacement: a solution
      worth trying in patients with residual aortic insufficiency.

PMID- 25060025
TI  - The superficial femoral artery conundrum: so close, yet so far away!

PMID- 25060024
TI  - Shared and differential factors influencing restenosis following endovascular
      therapy between TASC (Trans-Atlantic Inter-Society Consensus) II class A to C and
      D lesions in the femoropopliteal artery.
AB  - OBJECTIVES: This study sought to investigate factors associated with restenosis
      after endovascular therapy comparing TASC (Trans-Atlantic Inter-Society
      Consensus) II classes A to C with class D femoropopliteal (FP) lesions.
      BACKGROUND: It is unclear whether the determinants of restenosis for TASC II
      class D lesions are the same as those for TASC II classes A to C FP lesions.
      METHODS: We studied 2,400 limbs from 1,889 consecutive patients (73 +/- 17 years
      of age; 31% women; 30% critical limb ischemia) who underwent successful
      endovascular therapy for de novo FP lesions. Predictors for restenosis in TASC II
      classes A to C and class D lesions were assessed using a Cox proportional hazards
      model. RESULTS: The 5-year primary patency rate was 50% in TASC II classes A to C
      and 34% in TASC II class D lesions, respectively (p < 0.001). Overall, restenosis
      had a significant interaction with sex and renal failure (both p < 0.01). Female
      sex was a significant risk factor for restenosis in TASC II class D lesions
      (adjusted hazard ratio [HR]: 1.80, p < 0.001) but not TASC II classes A to C
      lesions (adjusted HR: 1.10, p = 0.352). Conversely, renal insufficiency was a
      significant risk factor for restenosis in TASC II classes A to C lesions
      (adjusted HR: 1.43, p < 0.001) but not TASC II class D lesions (adjusted HR:
      0.79, p = 0.129). Diabetes mellitus, no stent use, chronic total occlusion, and
      poor below-the-knee runoff were shared risk factors for restenosis between TASC
      II classes A to C and class D lesions (all p < 0.05). CONCLUSIONS: For de novo FP
      lesions, diabetes, no stent use, chronic total occlusion, and poor below-the-knee
      runoff were shared restenosis predictors for TASC II classes A to C and class D
      lesions, whereas renal failure was a predictor for TASC II classes A to C lesions
      and female sex for TASC II class D lesions.

PMID- 25060026
TI  - Impact of Watchman and Amplatzer devices on left atrial appendage adjacent
      structures and healing response in a canine model.
AB  - OBJECTIVES: This study was designed for conducting a comparative evaluation of
      the healing response after Watchman (WM) (Boston Scientific, Plymouth, Minnesota)
      and Amplatzer Cardiac Plug (ACP) (St. Jude Medical, Minneapolis, Minnesota) in a
      canine left atrial appendage (LAA) model. BACKGROUND: There is no direct
      comparison of the WM and ACP device in pre-clinical or clinical settings.
      METHODS: The LAA from canine (n = 6) and human (n = 19) hearts were compared to
      determine the feasibility of the canine model and its relevance to clinical
      applications. Subsequently, implantation of WM and ACP in the canine LAA was
      performed (n = 3 per device) to evaluate the device conformation to the LA
      anatomy as well as the healing response at 28 days. RESULTS: The LAA is a
      variable tubular structure in both canine and human hearts. Gross examination
      showed that the WM was properly seated inside the LAA ostium, in comparison to
      the ACP where the disk was outside of the LAA orifice and extended to the edge of
      the left superior pulmonary vein and mitral valve. At 28 days, complete neo
      endocardial coverage of the WM was observed; however, the ACP showed an
      incomplete covering on the disk surface especially at the lower edge and end
      screw hub regions. CONCLUSIONS: There are differences in conformation of LAA
      surrounding structures with variable healing response between WM and ACP after
      LAA closure in the canine model. WM does not obstruct or impact the LAA adjacent
      structures, resulting in a favorable surface recovery. In comparison, the disk of
      ACP could potentially jeopardize LAA neighboring structures and leads to delayed
      healing.

PMID- 25060027
TI  - Full polymer jacketing for long-segment spontaneous coronary artery dissection
      using bioresorbable vascular scaffolds.

PMID- 25060028
TI  - Valve migration into the left ventricular outflow tract managed by coaxial double
      valve alignment.

PMID- 25060029
TI  - Getting outside of our comfort zone.

PMID- 25060030
TI  - Percutaneous recanalization of occluded brachiocephalic vein-superior vena cava
      connection after resection of mediastinal mass.

PMID- 25060031
TI  - Acute myocardial infarction after Kawasaki disease.

PMID- 25060032
TI  - Multivessel spontaneous coronary artery dissection mimicking atherosclerosis.

PMID- 25060034
TI  - Localization of 9- and 13-oxo-octadecadienoic acids in tomato fruit.
AB  - We previously reported that the two peroxisome proliferator-activated receptor
      alpha agonists, 9- and 13-oxo-octadecadienoic acids (oxo-ODAs), were found in the
      tomato fruit. However, their localization remains unknown. Herein, we showed that
      oxo-ODAs localize primarily in the fruit peel and their amount increases after
      the homogenization of the tomato fruit. 

PMID- 25060033
TI  - Fear of recurrence: the importance of self-efficacy and satisfaction with care in
      gay men with prostate cancer.
AB  - OBJECTIVE: Limited research has investigated the psychosocial processes that
      underpin the effect of physical symptoms on fear of cancer recurrence.
      Additionally, despite evidence of increased vulnerability of marginalized
      populations to negative outcomes, few studies have examined the unique experience
      of gay men coping with the cancer process. The goals of this study were to
      determine whether disease-related self-efficacy and satisfaction with medical
      care mediated the relationship between greater physical symptoms and worse fear
      of recurrence among gay or bisexual prostate cancer survivors. METHODS:
      Participants were composed of 92 self-identified gay or bisexual men, who had
      received a diagnosis of prostate cancer in the past 4 years. Participants
      provided demographic information and completed self-report questionnaires that
      assessed symptom function, self-efficacy for prostate cancer symptoms,
      satisfaction with healthcare, and fear of recurrence. Bootstrapping procedures
      were used to assess for significant mediation. RESULTS: Results suggested
      significant mediation of the relationship between each of bowel, hormonal, and
      sexual function with fear of recurrence by self-efficacy and satisfaction with
      healthcare. Mediation was not significantly supported for the association between
      urinary function and fear of recurrence. CONCLUSIONS: Findings support the
      explanatory effects of self-efficacy for symptom management and satisfaction with
      healthcare on the relationship between symptom function and fear of recurrence.
      These results indicate that psychological processes, specifically psychological
      factors that hold particular relevance to gay or bisexual men, reflect a
      potential avenue for intervention to decrease fear of cancer recurrence.

PMID- 25060035
TI  - Caution or warning? A validity study of the MAYSI-2 with juvenile offenders.
AB  - Given the high prevalence of mental health and substance use disorders in the
      juvenile justice system and the emphasis on efficient screening and referrals,
      the current study sought to further validate the use of the Massachusetts Youth
      Screening Instrument version 2 (MAYSI-2). Using data from institutionalized
      delinquents (N=836) committed to the California Youth Authority, finite mixture
      modeling was employed to identify distinct latent classes based on MAYSI-2 scale
      scores. Identified classes were then compared across a range of covariates,
      including prior offenses, official records of misconduct, and multiple measures
      of mental health and psychological well-being. Findings revealed a three-class,
      gradient-based structure: low distress (n=380), moderate distress (n=327), and
      high distress (n=129). Overall, the MAYSI-2 identified juvenile offenders with
      mental health and substance use issues, but it did not differentiate youths with
      respect to offending patterns.

PMID- 25060036
TI  - Growth retardation and growth hormone deficiency in patients with Ataxia
      telangiectasia.
AB  - BACKGROUND: Ataxia telangiectasia (A-T) is a devastating human recessive disorder
      characterised by progressive cerebellar ataxia, immunodeficiency, genetic
      instability, and cancer susceptibility. In addition, many patients suffer from
      growth failure. METHODS: We analyzed growth and IGF-1/BP3 levels of 24 A-T
      patients compared with an age-matched group of healthy controls (n = 36).
      RESULTS: Ten (41.7%) A-T patients and none of healthy controls had an IGF-1 level
      below the 3rd percentile for age. The growth hormone (GH) stimulation tests
      revealed a severe GH deficiency with no increase of >5 ng/ml in six of the ten A
      T patients. The IGF-1 generation tests revealed normal increases in IGF-1 values
      in all patients. CONCLUSION: Our results show that a disturbance in the GH/IGF-1
      axis was present in 58.3% of A-T patients. Low levels of GH were the result of
      reduced central GH secretion. GH treatment may be a therapeutic option for A-T
      patients with severe growth failure.

PMID- 25060037
TI  - Cell-based assays for IGF-I bioactivity measurement: overview, limitations and
      current trends.
AB  - Insulin-like growth factor-I (IGF-I) is an important growth promoting protein
      that is involved in numerous cellular responses and multiple biological systems.
      Although the molecular structure, function and recombinant production of IGF-I in
      various hosts have been the subject of much researches over the recent past,
      methods to determine the bioactivity of this protein have not been fully
      explored. Several assays have traditionally been used to measure IGF-I
      bioactivity, but have not become a routine laboratory practice due to the high
      cost involved and technical problems. Thus, there is still a need for a rapid,
      technically simple and accurate assay to determine IGF-I bioactivity. This review
      highlights the various cell-based assays currently commercially available for
      measuring the bioactivity of IGF-I along with their limitations. This is aimed at
      presenting the modern-day IGF researcher with a holistic overview of the current
      trends and future prospects regarding IGF-I bioactivity determinations.

PMID- 25060038
TI  - The intersection of disability and healthcare disparities: a conceptual
      framework.
AB  - PURPOSE: This article provides a conceptual framework for understanding
      healthcare disparities experienced by individuals with disabilities. While health
      disparities are the result of factors deeply rooted in culture, life style,
      socioeconomic status, and accessibility of resources, healthcare disparities are
      a subset of health disparities that reflect differences in access to and quality
      of healthcare and can be viewed as the inability of the healthcare system to
      adequately address the needs of specific population groups. METHODS: This article
      uses a narrative method to identify and critique the main conceptual frameworks
      that have been used in analyzing disparities in healthcare access and quality,
      and evaluating those frameworks in the context of healthcare for individuals with
      disabilities. Specific models that are examined include the Aday and Anderson
      Model, the Grossman Utility Model, the Institute of Medicine (IOM)'s models of
      Access to Healthcare Services and Healthcare Disparities, and the Cultural
      Competency model. RESULTS: While existing frameworks advance understandings of
      disparities in healthcare access and quality, they fall short when applied to
      individuals with disabilities. Specific deficits include a lack of attention to
      cultural and contextual factors (Aday and Andersen framework), unrealistic
      assumptions regarding equal access to resources (Grossman's utility model), lack
      of recognition or inclusion of concepts of structural accessibility (IOM model of
      Healthcare Disparities) and exclusive emphasis on supply side of the healthcare
      equation to improve healthcare disparities (Cultural Competency model). In
      response to identified gaps in the literature and short-comings of current
      conceptualizations, an integrated model of disability and healthcare disparities
      is put forth. CONCLUSION: We analyzed models of access to care and disparities in
      healthcare to be able to have an integrated and cohesive conceptual framework
      that could potentially address issues related to access to healthcare among
      individuals with disabilities. The Model of Healthcare Disparities and Disability
      (MHDD) provides a framework for conceptualizing how healthcare disparities impact
      disability and specifically, how a mismatch between personal and environmental
      factors may result in reduced healthcare access and quality, which in turn may
      lead to reduced functioning, activity and participation among individuals with
      impairments and chronic health conditions. Researchers, health providers, policy
      makers and community advocate groups who are engaged in devising interventions
      aimed at reducing healthcare disparities would benefit from the discussions.
      Implications for Rehabilitation Evaluates the main models of healthcare disparity
      and disability to create an integrated framework. Provides a comprehensive
      conceptual model of healthcare disparity that specifically targets issues related
      to individuals with disabilities. Conceptualizes how personal and environmental
      factors interact to produce disparities in access to healthcare and healthcare
      quality. Recognizes and targets modifiable factors to reduce disparities between
      and within individuals with disabilities.

PMID- 25060039
TI  - The effects of practicing sitting Tai Chi on balance control and eye-hand
      coordination in the older adults: a randomized controlled trial.
AB  - PURPOSE: The purpose of this study was to examine the effects of 3 months of
      sitting Tai Chi training on the sitting balance control and eye-hand coordination
      of older adults subjects. METHODS: We randomly assigned 59 older adults from four
      residential care facilities to either sitting Tai Chi group or mobilizing
      exercises group as control. The sitting Tai Chi group underwent 3 months of
      training with a total of 36 sessions (1 hour/session, 3 sessions/week). The
      outcome measures included sitting balance tests (testing sequential weight
      shifting and forward reaching in a sitting position) and eye-hand coordination
      tests (reaction time, movement time and accuracy in finger pointing task).
      RESULTS: The Tai Chi practitioners showed significant improvement in their
      sequential weight shifting while sitting (improved by 29.0%, p <= 0.05) and in
      their maximum reaching distance from a sitting position (improved by 21.2%, p <=
      0.05). No such improvements were found in the control group. In the eye-hand
      coordination test, the sitting Tai Chi practitioners had significant improvements
      in accuracy (improved by 17.3%, p <= 0.05). Also, no improvement was found in the
      control group. CONCLUSIONS: The results demonstrate 3-months of sitting Tai Chi
      training can improve sitting balance and accuracy in finger pointing task in the
      older adults. IMPLICATIONS FOR REHABILITATION: Traditional Tai Chi poses
      difficulties for older adults with poor standing balance. This pilot study showed
      that a 3 months sitting Tai Chi training can improve sitting balance and accuracy
      in the finger pointing task in the older adults. Sitting Tai Chi can be a therapy
      option for older adults with poor standing balance.

PMID- 25060040
TI  - Confronting mortality: faith and meaning across cultures.
AB  - Despite advances in technology and medicine, death itself remains an immutable
      certainty. Indeed, the acceptance and understanding of our mortality are among
      the enduring metaphysical challenges that have confronted human beings from the
      beginning of time. How have we sought to cope with the inevitability of our
      mortality? How do various cultural and social representations of mortality shape
      and influence the way in which we understand and approach death? To what extent
      do personal beliefs and convictions about the meaning of life or the notion of an
      afterlife affect how we perceive and experience the process of death and dying?
      Steve Paulson, executive producer and host of To the Best of Our Knowledge,
      moderated a discussion on death, dying, and what lies beyond that included
      psychologist Lani Leary, professor of philosophy and religion Jeffrey J. Kripal,
      and sociologist Allan Kellehear. The following is an edited transcript of the
      discussion that occurred February 5, 7:00-8:30 pm, at the New York Academy of
      Sciences in New York City. 

PMID- 25060041
TI  - Modified Eu-doped Y2 O3 nanoparticles as turn-off luminescent probes for the
      sensitive detection of pyridoxine.
AB  - Europium-doped yttrium oxide nanoparticles (Y2 O3 :Eu NPs) modified by captopril
      were prepared in aqueous solution. In this study, we report the effect of
      pyridoxine hydrochloride on the photoluminescence intensity of Y2 O3 :Eu NPs in
      pH 7.2 buffer solution. By increasing the pyridoxine concentration, the
      luminescence intensity of Y2 O3 :Eu NPs is quenched. The results show that this
      method demonstrates high sensitivity for pyridoxine determination. A linear
      relationship is observed between 0.0 and 62.0 MUM with a correlation coefficient
      of 0.995 and a detection limit of 0.023 MUM.

PMID- 25060042
TI  - Endovascular recanalization of native chronic total occlusions in patients with
      failed lower-extremity bypass grafts.
AB  - PURPOSE: To investigate the feasibility, safety, and outcome of endovascular
      recanalization of native chronic total occlusions (CTOs) in patients with failed
      lower-extremity bypass grafts. MATERIALS AND METHODS: Retrospective review of 19
      limbs in 18 patients with failed lower-extremity bypass grafts that underwent
      recanalization of native arterial occlusions between February 2009 and April 2013
      was performed. Nine of the limbs presented with acute ischemia and 10 presented
      with chronic ischemia, including eight with critical limb ischemia and two with
      disabling claudication. RESULTS: The mean patency of the failed bypass grafts
      (63% venous) was 27 months. All limbs had Transatlantic Inter-Society Consensus
      class D lesions involving the native circulation. Technical success of the
      endovascular recanalization procedure was achieved in all but one limb (95%). The
      mean ankle brachial indices before and after treatment were 0.34 and 0.73,
      respectively. There were no major complications or emergency amputations. Mean
      patient follow-up was 64 weeks, and two patients were lost to follow-up. Primary
      patency rates at 3, 6, and 12 months were 87%, 48%, and 16%, respectively.
      Successful secondary procedures were performed in seven patients, with secondary
      patency rates at 3, 6, and 12 months of 88%, 73%, and 44%, respectively. Limb
      salvage rates at 12 and 24 months were 94% and 65%, and amputation-free survival
      rates at 12 and 24 months were 87% and 60%, respectively. CONCLUSIONS:
      Endovascular recanalization of native CTOs in patients with failed lower
      extremity bypass grafts is technically feasible and safe and results in
      acceptable limb salvage.

PMID- 25060043
TI  - Catalytic cleavage of ether C-O bonds by pincer iridium complexes.
AB  - The development of efficient catalytic methods to cleave the relatively
      unreactive C-O bonds of ethers remains an important challenge in catalysis.
      Building on our group's recent work, we report the dehydroaryloxylation of aryl
      alkyl ethers using pincer iridium catalysts. This method represents a rare fully
      atom-economical method for ether C-O bond cleavage.

PMID- 25060044
TI  - Effects of microwaves (950 MHZ mobile phone) on morphometric and apoptotic
      changes of rabbit epididymis.
AB  - The effect of mobile phone radiation on human reproduction system is still a
      matter of debate. In this study, 18 male rabbits were randomly divided into two
      experimental groups and one control group. Experimental groups received simulated
      microwaves with the frequency of 950 MHz and the output power of 3 and 6 watts
      for 2 weeks, 2 h a day. After a week of rest, the microscopic slides from the
      quada of the excised epididymis were prepared. Then, the diameter of epididymis,
      the height of epithelium and the number of apoptotic cells in epithelium in study
      groups were determined. The data were compared using spss software and one-way
      anova test. The epithelial height and diameter of the epididymis in 3 watt and 6
      watt groups had a significant decrease compared to the control group (P < 0.001),
      while the testosterone level only in 6 watt group was significantly decreased
      compared to control group. The rate of apoptosis in the epithelial cells of the
      epididymis had a significant increase only in 6 watt group compared to the
      control group (P < 0.001). This study showed that the microwaves with the
      frequency of 950 MHz can have negative impacts on morphometric and apoptotic
      changes of rabbit epididymis.

PMID- 25060045
TI  - Impact of malnutrition on propofol consumption and recovery time among patients
      undergoing laparoscopic gastrointestinal surgery.
AB  - BACKGROUND: Malnutrition is a major health problem, especially in hospitalized
      patients as it can be closely related to many post-operative complications.
      However, research on malnutrition and its effect on the outcome of general
      anesthesia have been largely neglected. Here we investigated malnutrition status
      on propofol consumption and recovery time among patients undergoing laparoscopic
      gastrointestinal surgery under general anesthesia. METHODS: One hundred and one
      patients were recruited between January and June 2012 at Tongji Hospital and
      assigned into three groups according to Nutritional Risk Screening Tool 2002
      score. A standard combined general anesthesia procedure was performed under
      regular monitoring. The dosage of propofol needed for induction, consumption
      during maintenance and recovery time were recorded. RESULTS: When compared with
      normal nutritional status individuals, the propofol dosage at induction was
      significantly decreased about 4.3% in moderate malnutritional status patients (P
      < 0.01) and about 16.8% in severely malnutritional status patients (P < 0.01).
      The average consumption of propofol was also significantly lower in malnourished
      individuals; for moderate malnutritional, the decrease was about 20% (P < 0.01)
      while for the severely malnutritional, it was 30% (P < 0.01) when compared with
      normal nutritional status individuals. For the recovery time of propofol
      anesthesia, the patients with severe malnutritional status awoke average 6.8 min
      later than those normally nourished (P < 0.01), but those patients with moderate
      malnutrition status did not (P = 0.885). CONCLUSION: The present results indicate
      that the dosage and recovery time of propofol does change in malnourished
      individuals. Therefore, malnutrition may somehow affect the outcome of general
      anesthesia.

PMID- 25060046
TI  - Scrotal cutaneous toxicity: an uncommon but important side-effect of sunitinib.

PMID- 25060047
TI  - Interstitial pregnancy: a 'road map' of surgical treatment based on a systematic
      review of the literature.
AB  - An electronic search concerning the surgical approach in cases of interstitial
      pregnancy from January 2000 to May 2013 has been carried out. Fifty three studies
      have been retrieved and included for statistical analysis. Conservative and
      radical surgical treatments in 354 cases of interstitial pregnancy are
      extensively described. Hemostatic techniques have been reported as well as
      clinical criteria for the medical approach. Surgical outcome in conservative
      versus radical treatment were similar. When hemostatic techniques were used,
      lower blood losses and lower operative times were recorded. Conversion to
      laparotomy involved difficulties in hemostasis and the presence of persistent or
      multiple adhesions. Laparoscopic injection of vasopressin into the myometrium
      below the cornual mass was the preferred approach.

PMID- 25060048
TI  - Radiation hybrid map of buffalo chromosome 7 detects a telomeric inversion
      compared to cattle chromosome 6.

PMID- 25060049
TI  - Ropivacaine for continuous wound infusion for postoperative pain management: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The use of continuous wound infusion (CWI) of local anaesthetics has
      been suggested as a safe and effective alternative technique to epidural
      anaesthesia/analgesia that allows surgeons to provide postoperative pain relief
      while reducing opioid consumption and associated adverse events. A previous meta
      analysis by Liu et al. [Am Coll Surg 2006;203:914-932] reported results mainly
      from studies of bupivacaine. Subsequently, several new randomized controlled
      trials (RCTs) of ropivacaine have been published. This systematic review and
      quantitative meta-analysis evaluates the efficacy of ropivacaine for CWI.
      METHODS: Systematic literature searches (EMBASE, MEDLINE) were performed to
      retrieve studies which met the following criteria: double-blind RCT of
      ropivacaine versus either placebo or an active comparator; use of ropivacaine
      solution without added active agents, and prohibition of other routine analgesics
      during the study period except rescue patient-controlled analgesia. For each
      included study, standardized effect sizes for ropivacaine versus placebo were
      calculated for opioid rescue use, pain score at rest, and pain score at
      mobilization. Meta-analyses were conducted for each endpoint. RESULTS: Fourteen
      RCTs comparing ropivacaine (n = 376) versus placebo (n = 380) were identified.
      Effect size estimates revealed significantly less opioid rescue use for
      ropivacaine patients (-1.3; 95% CI -1.5 to -1.1) and significantly less pain for
      ropivacaine patients both at rest (-1.1; 95% CI -1.3 to -0.9) and on mobilization
      (-1.5; 95% CI -1.7 to -1.3). The weighted mean reduction in opioid rescue use was
      22.4 mg. CONCLUSION: This systematic review and meta-analysis presents
      substantial evidence that ropivacaine provides clinically meaningful reductions
      in opioid use and pain outcomes. Ropivacaine CWI is effective for postoperative
      pain management in a wide range of surgical procedures.

PMID- 25060050
TI  - Decreased expression of Kallmann syndrome 1 sequence gene (KAL1) contributes to
      oral squamous cell carcinoma progression and significantly correlates with poorly
      differentiated grade.
AB  - BACKGROUND: Kallmann syndrome 1 sequence gene (KAL1) protein is an extracellular
      matrix associated protein which plays vital roles in neurons development and cell
      migration. However, its biological functions and clinical implications have yet
      not been revealed in oral carcinogenesis. The objective of the study was to
      evaluate the role of KAL1 in oral cancer and determine clinical significance of
      KAL1 in oral squamous cell carcinomas (OSCCs). METHODS: The expression pattern of
      KAL1 was examined in a testing cohort including OSCCs (n = 42) and paired
      adjacent tissues (PATs) (n = 14) by real-time PCR. The result was further
      validated in a validating cohort of OSCCs (n = 32). Correlation between
      clinicopathological parameters and KAL1 mRNA levels was analyzed by Kruskal
      Wallis test. In vitro, the effects of KAL1 ablation through siRNA-mediated
      knockdown on the proliferation of OSCC cells were determined by CCK-8, BrdU, and
      colonies formation assays, respectively. In addition, cell cycle distribution was
      further evaluated by cytometry. RESULTS: We observed that remarkably decreased
      expression of KAL1 mRNA in two independent cohorts (P = 0.0002 and P = 0.033,
      respectively). Furthermore, downregulated KAL1 mRNA was significantly associated
      with worse pathological grade (P = 0.013 and P = 0.035, respectively). Upon KAL1
      silencing, the proliferation and colonies formation potentials of OSCC cells were
      notably promoted by accelerating G1 to M phase transition. CONCLUSION: These data
      indicated that KAL1 plays a potential suppressive role on OSCC initiation and
      progression, and KAL1 gene may serve as an adjuvant biomarker for the
      identification of pathological grade.

PMID- 25060051
TI  - Asthma and respiratory physiology: putting lung function into perspective.
AB  - Bronchial asthma is a chronic disease characterized by airway
      hyperresponsiveness, airway inflammation and remodelling. The hypothesis that the
      illness is inflammatory in nature has recently been challenged by studies showing
      that airway smooth muscle (ASM) plays a more important role than previously
      thought. For example, it is now known that in asthma patients, ASM proliferates
      more and faster than in healthy subjects, carries intrinsic defects and exhibits
      impaired relaxation, increased velocity of shortening, plastic adaptation to
      short length and perturbed equilibrium of actin-to-myosin during cycling. Similar
      conclusions can be drawn from studies on airway mechanics. For instance, in
      asthma, abnormal ASM contributes to limiting the response to deep lung stretching
      and accelerates the return of bronchial tone to baseline conditions, and
      contributes to increased airway stiffness. Upon stimulation, ASM causes airway
      narrowing that is heterogeneous across the lung and variable over time. This
      heterogeneity leads to patchy ventilation. Experimental studies have shown that
      patchy ventilation may precipitate an asthma attack, and inability to maintain
      bronchial tone control over time can predict the occurrence of bronchospastic
      attacks over a matter of a few days. To improve our knowledge on the pathogenesis
      of asthma, we believe that it is necessary to explore the disease within the
      framework of the topographical, volume and time domains of the lung that play an
      important role in setting the severity and progression of the disease.
      Application of the forced oscillation technique and multiple breath nitrogen
      washout may, alone or in combination, help address questions unsolvable until
      now. 

PMID- 25060052
TI  - Serum fibroblast growth factor-23 is associated with incident kidney disease.
AB  - Fibroblast growth factor-23 is a bone-derived hormone that increases urinary
      phosphate excretion and inhibits hydroxylation of 25-hydroxyvitamin D. Recent
      studies suggest that fibroblast growth factor-23 may be an early biomarker of CKD
      progression. However, its role in kidney function decline in the general
      population is unknown. We assessed the relationship between baseline (1990-1992)
      serum levels of intact fibroblast growth factor-23 and incident ESRD in 13,448
      Atherosclerosis Risk in Communities study participants (56.1% women, 74.7% white)
      followed until December 31, 2010. At baseline, the mean age of participants was
      56.9 years and the mean eGFR was 97 ml/min per 1.73 m(2). During a median follow
      up of 19 years, 267 participants (2.0%) developed ESRD. After adjustment for
      demographic characteristics, baseline eGFR, traditional CKD risk factors, and
      markers of mineral metabolism, the highest fibroblast growth factor-23 quintile
      (>54.6 pg/ml) compared with the lowest quintile (<32.0 pg/ml) was associated with
      risk of developing ESRD (hazard ratio, 2.10; 95% confidence interval, 1.31 to
      3.36; trend P<0.001). In a large, community-based study comprising a broad range
      of kidney function, higher baseline fibroblast growth factor-23 levels were
      associated with increased risk of incident ESRD independent of the baseline level
      of kidney function and a number of other risk factors. 

PMID- 25060054
TI  - Cutting it out: ENaC processing in the human nephron.

PMID- 25060053
TI  - Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with
      resistance to immunosuppression.
AB  - In children, sporadic nephrotic syndrome can be related to a genetic cause, but
      to what extent genetic alterations associate with resistance to immunosuppression
      is unknown. In this study, we designed a custom array for next-generation
      sequencing analysis of 19 target genes, reported as possible causes of nephrotic
      syndrome, in a cohort of 31 children affected by sporadic steroid-resistant
      nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive
      clinical phenotype. Patients who exhibited extrarenal symptoms, had a familial
      history of the disease or consanguinity, or had a congenital onset were excluded.
      We identified a genetic cause in 32.3% of the children with steroid-resistant
      disease but zero of 38 children with steroid-sensitive disease. Genetic
      alterations also associated with lack of response to immunosuppressive agents in
      children with steroid-resistant disease (0% of patients with alterations versus
      57.9% of patients without alterations responded to immunosuppressive agents),
      whereas clinical features, age at onset, and pathologic findings were similar in
      steroid-resistant patients with and without alterations. These results suggest
      that heterogeneous genetic alterations in children with sporadic forms of
      nephrotic syndrome associate with resistance to steroids as well as
      immunosuppressive treatments. In these patients, a comprehensive screening using
      such an array may, thus, be useful for genetic counseling and may help clinical
      decision making in a fast and cost-efficient manner. 

PMID- 25060055
TI  - The biomarker niche for fibroblast growth factor 23 testing in CKD.

PMID- 25060057
TI  - The epithelial sodium channel gamma-subunit is processed proteolytically in human
      kidney.
AB  - The epithelial sodium channel (ENaC) of the kidney is necessary for extracellular
      volume homeostasis and normal arterial BP. Activity of ENaC is enhanced by
      proteolytic cleavage of the gamma-subunit and putative release of a 43-amino acid
      inhibitory tract from the gamma-subunit ectodomain. We hypothesized that
      proteolytic processing of gammaENaC occurs in the human kidney under physiologic
      conditions and that proteinuria contributes to aberrant proteolytic activation.
      Here, we used monoclonal antibodies (mAbs) with specificity to the human 43-mer
      inhibitory tract (N and C termini, mAbinhibit, and mAb4C11) and the neoepitope
      generated after proteolytic cleavage at the prostasin/kallikrein cleavage site
      (K181-V182 and mAbprostasin) to examine human nephrectomy specimens. By
      immunoblotting, kidney cortex homogenate from patients treated with angiotensin
      II type 1 receptor antagonists (n=6) or angiotensin-converting enzyme inhibitors
      (n=6) exhibited no significant difference in the amount of full-length or furin
      cleaved gammaENaC or the furin-cleaved-to-full-length ratio of gammaENaC compared
      with homogenate from patients on no medication (n=5). Patients treated with
      diuretics (n=4) displayed higher abundance of full-length and furin-cleaved
      gammaENaC, with no significant change in the furin-cleaved-to-full-length
      gammaENaC ratio. In patients with proteinuria (n=6), the inhibitory tract was
      detected only in full-length gammaENaC by mAbinhibit. Prostasin/kallikrein
      cleaved gammaENaC was detected consistently only in tissue from patients with
      proteinuria and observed in collecting ducts. In conclusion, human kidney
      gammaENaC is subject to proteolytic cleavage, yielding fragments compatible with
      furin cleavage, and proteinuria is associated with cleavage at the putative
      prostasin/kallikrein site and removal of the inhibitory tract within gammaENaC. 

PMID- 25060058
TI  - Exonic mutations in the SLC12A3 gene cause exon skipping and premature
      termination in Gitelman syndrome.
AB  - A variety of genetic backgrounds cause the loss of function of thiazide-sensitive
      sodium chloride cotransporter, encoded by SLC12A3, responsible for the phenotypes
      in Gitelman syndrome. Recently, the phenomenon of exon skipping, in which exonic
      mutations result in abnormal splicing, has been associated with various diseases.
      Specifically, mutations in exonic splicing enhancer (ESE) sequences can promote
      exon skipping. Here, we used a bioinformatics program to analyze 88 missense
      mutations in the SLC12A3 gene and identify candidate mutations that may induce
      exon skipping. The three candidate mutations that reduced ESE scores the most
      were further investigated by minigene assay, and two (p.A356V and p.M672I) caused
      abnormal splicing in vitro. Furthermore, we identified the p.M672I (c.2016G>A)
      mutation in a patient with Gitelman syndrome and found that this single
      nucleotide mutation causes exclusion of exon 16 in the SLC12A3 mRNA transcript.
      Functional analyses revealed that the protein encoded by the aberrant SLC12A3
      transcript does not transport sodium. These results suggest that aberrant exon
      skipping is one previously unrecognized mechanism by which missense mutations in
      SLC12A3 can lead to Gitelman syndrome. 

PMID- 25060056
TI  - Ferric citrate controls phosphorus and delivers iron in patients on dialysis.
AB  - Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and
      are iron deficient. We studied ferric citrate as a phosphorus binder and iron
      source. In this sequential, randomized trial, 441 subjects on dialysis were
      randomized to ferric citrate or active control in a 52-week active control period
      followed by a 4-week placebo control period, in which subjects on ferric citrate
      who completed the active control period were rerandomized to ferric citrate or
      placebo. The primary analysis compared the mean change in phosphorus between
      ferric citrate and placebo during the placebo control period. A sequential
      gatekeeping strategy controlled study-wise type 1 error for serum ferritin,
      transferrin saturation, and intravenous iron and erythropoietin-stimulating agent
      usage as prespecified secondary outcomes in the active control period. Ferric
      citrate controlled phosphorus compared with placebo, with a mean treatment
      difference of -2.2+/-0.2 mg/dl (mean+/-SEM) (P<0.001). Active control period
      phosphorus was similar between ferric citrate and active control, with comparable
      safety profiles. Subjects on ferric citrate achieved higher mean iron parameters
      (ferritin=899+/-488 ng/ml [mean+/-SD]; transferrin saturation=39%+/-17%) versus
      subjects on active control (ferritin=628+/-367 ng/ml [mean+/-SD]; transferrin
      saturation=30%+/-12%; P<0.001 for both). Subjects on ferric citrate received less
      intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active
      control; P<0.001) and less erythropoietin-stimulating agent (median epoetin
      equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active
      control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate.
      Thus, ferric citrate is an efficacious and safe phosphate binder that increases
      iron stores and reduces intravenous iron and erythropoietin-stimulating agent use
      while maintaining hemoglobin. 

PMID- 25060059
TI  - Dysregulation of autoantigen genes in ANCA-associated vasculitis involves
      alternative transcripts and new protein synthesis.
AB  - Proteinase 3 (PR3) and myeloperoxidase (MPO) are two major autoantigens in
      patients with vasculitis with ANCA. The genes encoding these autoantigens are
      abnormally expressed in peripheral granulocytes of patients with active ANCA
      associated vasculitis. This study provides evidence that this transcriptional
      dysregulation results in a variety of mRNA processing events from the PRTN3 gene
      locus. In addition to elevated levels of PR3 message, leukocyte RNA from patients
      contained PR3 transcripts with an alternative 3' untranslated region.
      Furthermore, we detected usage of an alternative transcription start site within
      intron 1 of the PRTN3 gene locus that coincided with active disease (odds ratio,
      3.3; 95% confidence interval, 1.3 to 8.4; P=0.01). This promoter may be
      developmentally regulated, because it was active in normal human bone marrow,
      multiple leukemia cell lines, MCF-7 cells, and subjects after GM-CSF treatment
      but not subjects with a neutrophil left shift. This transcript, which lacks exon
      1 of PRTN3, encodes a 24-kD protein (p24(PR3/MBN)) with a sequence similar to
      that previously described for myeloblastin. Notably, PR3, p24(PR3/MBN), and MPO
      were synthesized in cultured neutrophils from patients with active ANCA
      associated vasculitis, indicating that increased transcription results in newly
      synthesized autoantigens in peripheral neutrophils of patients. The synthesis of
      p24(PR3/MBN) seems to expand the autoantigen repertoire, because immunoblots
      showed that sera from patients recognized p24(PR3/MBN). These findings emphasize
      the importance of transcriptional dysregulation of the autoantigen in autoimmune
      disease. 

PMID- 25060060
TI  - A potential role for mechanical forces in the detachment of podocytes and the
      progression of CKD.
AB  - Loss of podocytes underlies progression of CKD. Detachment of podocytes from the
      glomerular basement membrane (GBM) rather than apoptosis or necrosis seems to be
      the major mechanism of podocyte loss. Such detachment of viable podocytes may be
      caused by increased mechanical distending and shear forces and/or impaired
      adhesion to the GBM. This review considers the mechanical challenges that may
      lead to podocyte loss by detachment from the GBM under physiologic and
      pathophysiologic conditions, including glomerular hypertension, hyperfiltration,
      hypertrophy, and outflow of filtrate from subpodocyte spaces. Furthermore, we
      detail the cellular mechanisms by which podocytes respond to these challenges,
      discuss the protective effects of angiotensin blockade, and note the questions
      that must be addressed to better understand the relationship between podocyte
      detachment and progression of CKD. 

PMID- 25060063
TI  - Nano-TiO2 modulates the dermal sensitization potency of dinitrochlorobenzene
      after topical exposure.
AB  - BACKGROUND: Little is known about the impact of engineered nanoparticles (ENPs)
      on skin sensitization caused by chemicals. OBJECTIVES: We determined the ability
      of different ENPs (TiO2 , Ag and SiO2 ) and aged paint particles containing ENPs
      to modulate dermal sensitization by a known potent dermal sensitizer. METHODS:
      The fur of BALB/c mice in the area around the ears was cut with scissors 1 day
      prior to topical exposure to ENPs (0.4, 4 or 40 mg mL(-1) ), paint particles
      containing ENPs (4 mg mL(-1) ) or vehicle (day 0). On days 1, 2 and 3, the mice
      received dermal applications on the back of both ears of 2,4-dinitrochlorobenzene
      (DNCB) or vehicle. The stimulation index (SI) was calculated on day 6. RESULTS:
      Topical exposure to TiO2 , Ag or SiO2 ENPs, or aged paint particles followed by
      vehicle treatment as a control, did not influence the SI. When 4 mg mL(-1) TiO2
      ENPs were applied prior to DNCB sensitization, we found an increased SI compared
      with vehicle-exposed mice prior to DNCB sensitization. Furthermore, an increased
      titanium concentration was found in the draining lymph node cells of this group.
      Topical exposure to Ag or SiO2 ENPs or aged paint particles prior to DNCB
      sensitization did not influence the SI. CONCLUSIONS: We have demonstrated that
      topical exposure to TiO2 ENPs increases chemical-induced dermal sensitization.

PMID- 25060062
TI  - Presence of an umbilical artery notch in monochorionic/monoamniotic twins.
AB  - OBJECTIVE: To examine the association between an umbilical artery notch and fetal
      deterioration in monochorionic/monoamniotic (MC/MA) twins. METHODS: Six MC/MA
      twin pregnancies were admitted at 24-28 weeks of gestation for close fetal
      surveillance until elective delivery at 32 weeks or earlier in the presence of
      signs of fetal deterioration. Ultrasound (US) examinations were performed twice
      weekly. The presence of cord entanglement, umbilical artery notch, abnormal
      Doppler parameters, a non-reassuring fetal heart rate pattern, or an abnormal
      fetal biophysical profile were evaluated. RESULTS: Umbilical cord entanglement
      was observed on US in all pregnancies. The presence of an umbilical artery notch
      was noted in four out of six pregnancies and in two of them an umbilical artery
      notch was seen in both twins. The umbilical artery pulsatility index was normal
      in all fetuses. Doppler parameters of the middle cerebral artery and ductus
      venosus, fetal biophysical profile and fetal heart rate monitoring remained
      normal until delivery in all pregnancies. All neonates experienced morbidity
      related to prematurity; however, all were discharged home in good condition.
      CONCLUSION: The presence of an umbilical artery notch and cord entanglement,
      without other signs of fetal deterioration, are not indicative of an adverse
      perinatal outcome.

PMID- 25060064
TI  - Mechanical Thrombectomy in Acute Occlusion of the Carotid-T: A Retrospective
      Single Centre Study in 51 Patients.
AB  - BACKGROUND AND PURPOSE: Acute occlusion of the carotid-T is associated with large
      ischemic lesions, poor outcome and up to 53 % mortality with conservative
      therapy. Endovascular mechanical thrombectomy (EMT) is a promising alternative
      treatment of large vessel occlusion. Here, we examine feasibility, safety and
      efficiency of EMT in acute ischemic stroke due to carotid-T-occlusion. METHODS:
      Single centre, retrospective analysis of 51 consecutive patients with acute
      occlusion of the carotid-T, treated by EMT within 6 h after symptom onset. Most
      patients (42/51) were treated with stentretrievers, 33 with stentretrievers only.
      Recanalization was assessed by the Thrombolysis in Cerebral Infarction (TICI)
      score. Early and mid-term clinical outcome was evaluated by National Institutes
      of Health Stroke Scale (NIHSS)- and modified Rankin Scale mRS-scores,
      respectively. RESULTS: Successful recanalization (TICI 2b/3) was achieved in 78.4
      % (40/51). Good clinical outcome (mRS 0-2) was observed in 24.4 % of patients,
      and only in patients treated successfully (TICI 2b/3). Stentretrievers yielded
      higher recanalization rates and better clinical outcomes than non-stentretriever
      devices. A total of 12 patients died (29.3 %) during the 90-day observation
      period. Clinically relevant procedure-related complications occurred in two
      patients, consisting in one vessel perforation with a microwire, and one
      symptomatic parenchymal haemorrhage after initiation of antiplatelet therapy
      following the inadvertent detachment of a stentretriever. Another symptomatic
      haemorrhage, not directly procedure-related, occurred in one additional patient.
      CONCLUSION: EMT in acute carotid-T-occlusion is efficient, yielding high
      recanalization rates, and reasonably safe, with a low rate of clinically relevant
      complications. Successful recanalization seems to be a prerequisite for good
      clinical outcome in this severe condition.

PMID- 25060065
TI  - Pretargeted immunoPET of prostate cancer with an anti-TROP-2 x anti-HSG
      bispecific antibody in mice with PC3 xenografts.
AB  - PURPOSE: Pretargeting with bispecific antibodies and radiolabeled hapten-peptides
      could be used to specifically target tumors with high target-to-background
      ratios. TF12 is a trivalent bispecific antibody that consists of two anti-TROP-2
      Fab fragments and one anti-HSG (histamine-succinyl-glycine) Fab fragment. The
      TROP-2 antigen is expressed in many epithelial cancers, including prostate cancer
      (PC), and therefore, this bispecific antibody can be used for pretargeting of PC.
      In this study, the potential for pretargeted radioimmunoPET with TF12 and the
      (68)Ga-labeled di-HSG peptide IMP288 in mice with human PC xenografts was
      investigated using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) as a reference.
      PROCEDURES: The potential of pretargeted immunoPET with TF12 and the (68)Ga
      labeled di-HSG hapten-peptide, IMP288, was studied in mice with subcutaneous PC3
      tumors using [(18)F]FDG as a reference. Furthermore, the use of this pretargeting
      system for imaging PC lesions was evaluated in mice with intraperitoneally
      growing tumors with [(18)F]FDG as a reference. RESULTS: [(68)Ga]lMP288 showed
      rapid accumulation in the TF12 pretargeted subcutaneous tumor (7.2 +/- 1.1 %
      ID/g) with low uptake in the kidneys (1.8 +/- 0.5 % ID/g) and high tumor-to-blood
      ratios (17.4 +/- 11.2) at 1 h p.i. Accumulation of [(18)F]FDG in the s.c. tumors
      was significantly lower (3.4 +/- 0.9 % ID/g, P = 0.008), with lower tumor-to
      blood ratios (3.0 +/- 1.9, P = 0.011). ImmunoPET/CT images clearly visualized
      both subcutaneous and intraperitoneal tumors as small as 5 mm(3) with low blood
      levels and kidney uptake as early as 1 h p.i. CONCLUSION: Pretargeted immunoPET
      with TF12 in combination with a (68)Ga-labeled hapten-peptide is an efficient
      system for rapid, sensitive, and specific imaging of prostate cancer.

PMID- 25060066
TI  - Ultrafast photo-induced ligand solvolysis of cis
      [Ru(bipyridine)2(nicotinamide)2](2+): experimental and theoretical insight into
      its photoactivation mechanism.
AB  - Mechanistic insight into the photo-induced solvent substitution reaction of cis
      [Ru(bipyridine)2(nicotinamide)2](2+) (1) is presented. Complex 1 is a photoactive
      species, designed to display high cytotoxicity following irradiation, for
      potential use in photodynamic therapy (photochemotherapy). In Ru(II) complexes of
      this type, efficient population of a dissociative triplet metal-centred ((3)MC)
      state is key to generating high quantum yields of a penta-coordinate intermediate
      (PCI) species, which in turn may form the target species: a mono-aqua
      photoproduct [Ru(bipyridine)2(nicotinamide)(H2O)](2+) (2). Following irradiation
      of 1, a thorough kinetic picture is derived from ultrafast UV/Vis transient
      absorption spectroscopy measurements, using a 'target analysis' approach, and
      provides both timescales and quantum yields for the key processes involved. We
      show that photoactivation of 1 to 2 occurs with a quantum yield >=0.36, all
      within a timeframe of ~400 ps. Characterization of the excited states involved,
      particularly the nature of the PCI and how it undergoes a geometry relaxation to
      accommodate the water ligand, which is a keystone in the efficiency of the
      photoactivation of 1, is accomplished through state-of-the-art computation
      including complete active space self-consistent field methods and time-dependent
      density functional theory. Importantly, the conclusions here provide a detailed
      understanding of the initial stages involved in this photoactivation and the
      foundation required for designing more efficacious photochemotherapy drugs of
      this type.

PMID- 25060067
TI  - The Panama Canal and the transoceanic dispersal of marine invertebrates:
      evaluation of the introduced amphipod Paracaprella pusilla Mayer, 1890 in the
      Pacific Ocean.
AB  - Although the Panama Canal is one of the major corridors for shipping and
      potential dispersal of marine invaders in the tropics, little is known about the
      effect that the Canal has had on the distribution of marine biota. In this study,
      we (a) document the existence of established populations of the Western Atlantic
      caprellid amphipod Paracaprella pusilla, Mayer, 1890 for the first time at the
      Pacific entrance to the Canal, (b) review its distribution in the Pacific Ocean,
      and (c) evaluate possible mechanisms of introduction. The confirmed distribution
      of P. pusilla in the Pacific Ocean is limited to Australia, Hawaii, and Panama,
      despite earlier published reports from Chile and China. Laboratory experiments
      demonstrated intolerance of P. pusilla to freshwater, causing 100% mortality, and
      suggest invasion of the Pacific coast of Panama occurred through the Canal via
      ships' ballast water or by secondary spread via ships (ballast water or hull
      fouling) from another Pacific region. 

PMID- 25060068
TI  - Recent benthic foraminiferal assemblages and their relationship to environmental
      variables on the shoreface and inner shelf off Valencia (western Mediterranean).
AB  - The environmental variables that determine the distributions of benthic
      foraminiferal assemblages on the shoreface and inner shelf of the north of
      Valencia province (Western Mediterranean) are identified. The possible influence
      of variables such as water depth, distance from shore, hydrodynamics, substrate
      type, carbonate content, organic matter content and human activity is evaluated.
      Multivariate cluster-Q-type analysis and redundancy analysis (RDA) are used to
      identify the environmental variables that have the greatest influence on the
      assemblage distribution. The spatial distribution of the assemblages is closely
      associated with water depth and substrate. The diversity and abundance of
      foraminifera shells increase with depth and their conservation improves. The most
      common species in the study area are Ammonia beccarii, Rosalina globularis,
      Buccella granulata, Planorbulina mediterranensis, and Lobatula lobatula. The
      presence of wastewater in the study area has not polluted the foraminiferal
      assemblages (absence of anomalous shells). The direction of the discharge plume
      is a potential source of nutrients for deep water. 

PMID- 25060069
TI  - Inhibition and mechanism of HDAC8 revisited.
AB  - Histone deacetylases (HDACs) have found intense interest as drug targets for a
      variety of diseases, but there is disagreement about basic aspects of the
      inhibition and mechanism of HDACs. QM/MM calculations of HDAC8 including a large
      QM region provide a model that is consistent with the available crystal
      structures and structure-activity relationships of different HDAC inhibitors. The
      calculations support a spontaneous proton transfer from a hydroxamic acid to an
      active site histidine upon binding to the zinc. The role of the H142/D176
      catalytic dyad as the general base of the reaction is elucidated. The reasons for
      the disagreements between previous proposals are discussed. The results provide
      detailed insights into the unique mechanism of HDACs, including the role of the
      two catalytic dyads and function of the potassium near the active site. They also
      have important implications for the design of novel inhibitors for a number of
      HDACs such as the class IIa HDACs. 

PMID- 25060070
TI  - CBB1003, a lysine-specific demethylase 1 inhibitor, suppresses colorectal cancer
      cells growth through down-regulation of leucine-rich repeat-containing G-protein
      coupled receptor 5 expression.
AB  - PURPOSE: Lysine-specific demethylase 1 (LSD1) was highly expressed in several
      malignancies and had been implicated in pathological processes of cancer cells.
      However, the role of LSD1 in colorectal cancer (CRC) carcinogenesis, prognosis
      and treatment remains uncharacterized. METHODS: In this study, we examined LSD1
      expression in paraffin-embedded CRC specimens from 295 patients, including 65
      patients with paired samples of colorectal carcinoma, adjacent adenoma and normal
      colorectal tissues. Using an LSD1 inhibitor, CBB1003, as a probe, we studied the
      association between LSD1 and leucine-rich repeat-containing G-protein-coupled
      receptor 5 (LGR5), a CRC stem cell marker involved in carcinogenesis. The anti
      tumor effects of CBB1003 on CRC cells were also examined. RESULTS: LSD1
      expression was significantly elevated in colorectal tumor tissues compared with
      adjacent adenoma and normal colorectal tissues (P < 0.001), and LSD1 levels were
      significantly correlated with an advanced AJCC T stage (P = 0.012) and distant
      metastasis (P = 0.004). CBB1003 inhibited CRC cell proliferation and colony
      formation. In cultured CRC cells, inhibiting LSD1 activity by CBB1003 caused a
      decrease in LGR5 levels while overexpression of LGR5 reduced CBB1003-induced cell
      death. We also observed the inactivation of beta-catenin/TCF signaling after
      CBB1003 treatment, consistent with the positive correlations among LSD1, LGR5,
      beta-catenin and c-Myc expression in human colon tumor and adenoma tissues.
      CONCLUSION: Our result suggested that LSD1 overexpression promotes CRC
      development and that the LSD1 inhibitor inhibits CRC cell growth by down
      regulating LGR5 levels and inactivates the Wnt/beta-catenin pathway. Thus, LSD1
      and its inhibitor might provide a new target or a useful strategy for therapy of
      CRC.

PMID- 25060071
TI  - Developing estimates of frequency and intensity of exposure to three types of
      metalworking fluids in a population-based case-control study of bladder cancer.
AB  - BACKGROUND: A systematic, transparent, and data-driven approach was developed to
      estimate frequency and intensity of exposure to straight, soluble, and
      synthetic/semi-synthetic metalworking fluids (MWFs) within a case-control study
      of bladder cancer in New England. METHODS: We assessed frequency using individual
      level information from job-specific questionnaires wherever possible, then
      derived and applied job group-level patterns to likely exposed jobs with less
      information. Intensity estimates were calculated using a statistical model
      developed from measurements and determinants extracted from the published
      literature. RESULTS: For jobs with probabilities of exposure>=0.5, median
      frequencies were 8-10 hr/week, depending on MWF type. Median intensities for
      these jobs were 2.5, 2.1, and 1.0 mg/m3 for soluble, straight, and synthetic/semi
      synthetic MWFs, respectively. CONCLUSIONS: Compared to case-by-case assessment,
      these data-driven decision rules are transparent and reproducible and may result
      in less biased estimates. These rules can also aid future exposure assessments of
      MWFs in population-based studies.

PMID- 25060073
TI  - Effect of changes in pelvic tilt on range of motion to impingement and
      radiographic parameters of acetabular morphologic characteristics.
AB  - BACKGROUND: The current understanding of the effect of dynamic changes in pelvic
      tilt on the functional acetabular orientation and occurrence of femoroacetabular
      impingement (FAI) is limited. PURPOSE: To determine the effect of changes in
      pelvic tilt on (1) terminal hip range of motion and (2) measurements of
      acetabular version as assessed on 2- and 3-dimensional imaging. STUDY DESIGN:
      Controlled laboratory study. METHODS: Preoperative pelvic computed tomographic
      scans of 48 patients (50 hips) who underwent arthroscopic surgery for the
      treatment of FAI were analyzed. The mean age of the study population was 25.7
      years (range, 14-56 years), and 56% were male. Three-dimensional models of the
      hips were created, allowing manipulation of the pelvic tilt and simulation of hip
      range of motion to osseous contact. Acetabular version was measured and the
      presence of the crossover sign, prominent ischial spine sign, and posterior wall
      sign was recorded on simulated plain radiographs. Measurements of range of motion
      to bony impingement during (1) hip flexion, (2) internal rotation in 90 degrees 
      of flexion, and (3) internal rotation in 90 degrees  of flexion and 15 degrees 
      adduction were performed, and the location of bony contact between the proximal
      femur and acetabular rim was defined. These measurements were calculated for -10
      degrees  (posterior), 0 degrees  (native), and +10 degrees  (anterior) pelvic
      orientations. RESULTS: In native tilt, mean cranial acetabular version was 3.3
      degrees , while central version averaged 16.2 degrees . Anterior pelvic tilt (10
      degrees  change) resulted in significant retroversion, with mean decreases in
      cranial and central version of 5.9 degrees  and 5.8 degrees , respectively (P <
      .0001 for both). Additionally, this resulted in a significantly increased
      proportion of positive crossover, posterior wall, and prominent ischial spine
      signs (P < .001 for all). Anterior pelvic tilt (10 degrees  change) resulted in a
      decrease in internal rotation in 90 degrees  of flexion of 5.9 degrees  (P <
      .0001) and internal rotation in 90 degrees  of flexion and 15 degrees  adduction
      of 8.5 degrees  (P < .0001), with a shift in the location of osseous impingement
      more anteriorly. Posterior pelvic tilt (10 degrees  change) resulted in an
      increase in internal rotation in 90 degrees  of flexion of 5.1 degrees  (P <
      .0001) and internal rotation in 90 degrees  of flexion and 15 degrees  adduction
      of 7.4 degrees  (P < .0001), with a superolateral shift in the location of
      osseous impingement. CONCLUSION/CLINICAL RELEVANCE: Dynamic changes in pelvic
      tilt significantly influence the functional orientation of the acetabulum and
      must be considered. Dynamic anterior pelvic tilt is predicted to result in
      earlier occurrence of FAI in the arc of motion, whereas dynamic posterior pelvic
      tilt results in later occurrence of FAI, which may have implications regarding
      nonsurgical treatments for FAI.

PMID- 25060074
TI  - Heart rate autonomic regulation system at rest and during paced breathing among
      patients with CRPS as compared to age-matched healthy controls.
AB  - OBJECTIVE: The objective of this study is to assess the autonomic nerve heart
      rate regulation system at rest and its immediate response to paced breathing
      among patients with complex regional pain syndrome (CRPS) as compared with age
      matched healthy controls. DESIGN: Quasiexperimental. SETTING: Outpatient clinic.
      SUBJECTS: Ten patients with CRPS and 10 age- and sex-matched controls. METHODS:
      Participants underwent Holter ECG (NorthEast Monitoring, Inc., Maynard, MA, USA)
      recording during rest and biofeedback-paced breathing session. Heart rate
      variability (HRV), time, and frequency measures were assessed. RESULTS: HRV and
      time domain values were significantly lower at rest among patients with CRPS as
      compared with controls. A significant association was noted between pain rank and
      HRV frequency measures at rest and during paced breathing; although both groups
      reduced breathing rate significantly during paced breathing, HRV time domain
      parameters increased only among the control group. CONCLUSIONS: The increased
      heart rate and decreased HRV at rest in patients with CRPS suggest a general
      autonomic imbalance. The inability of the patients to increase HRV time domain
      values during paced breathing may suggest that these patients have sustained
      stress response with minimal changeability in response to slow-paced breathing
      stimuli.

PMID- 25060072
TI  - Protective equipment and player characteristics associated with the incidence of
      sport-related concussion in high school football players: a multifactorial
      prospective study.
AB  - BACKGROUND: The incidence of sport-related concussion (SRC) in high school
      football is well documented. However, limited prospective data are available
      regarding how player characteristics and protective equipment affect the
      incidence of SRC. PURPOSE: To determine whether the type of protective equipment
      (helmet and mouth guard) and player characteristics affect the incidence of SRC
      in high school football players. DESIGN: Cohort study; Level of evidence, 2.
      METHODS: Certified athletic trainers (ATs) at each high school recorded the type
      of helmet worn (brand, model, purchase year, and recondition status) by each
      player as well as information regarding players' demographics, type of mouth
      guard used, and history of SRC. The ATs also recorded the incidence and days lost
      from participation for each SRC. Incidence of SRC was compared for various
      helmets, type of mouth guard, history of SRC, and player demographics. RESULTS: A
      total of 2081 players (grades 9-12) enrolled during the 2012 and/or 2013 football
      seasons (2287 player-seasons) and participated in 134,437 football (practice or
      competition) exposures. Of these players, 206 (9%) sustained a total of 211 SRCs
      (1.56/1000 exposures). There was no difference in the incidence of SRC (number of
      helmets, % SRC [95% CI]) for players wearing Riddell (1171, 9.1% [7.6%-11.0%]),
      Schutt (680, 8.7% [6.7%-11.1%]), or Xenith (436, 9.2% [6.7%-12.4%]) helmets.
      Helmet age and recondition status did not affect the incidence of SRC. The rate
      of SRC (hazard ratio [HR]) was higher in players who wore a custom mouth guard
      (HR = 1.69 [95% CI, 1.20-2.37], P < .001) than in players who wore a generic
      mouth guard. The rate of SRC was also higher (HR = 1.96 [95% CI, 1.40-2.73], P <
      .001) in players who had sustained an SRC within the previous 12 months (15.1% of
      the 259 players [95% CI, 11.0%-20.1%]) than in players without a previous SRC
      (8.2% of the 2028 players [95% CI, 7.1%-9.5%]). CONCLUSION: Incidence of SRC was
      similar regardless of the helmet brand (manufacturer) worn by high school
      football players. Players who had sustained an SRC within the previous 12 months
      were more likely to sustain an SRC than were players without a history of SRC.
      Sports medicine providers who work with high school football players need to
      realize that factors other than the type of protective equipment worn affect the
      risk of SRC in high school players.

PMID- 25060075
TI  - Iatrogenic injury to posterior antebrachial cutaneous nerve.

PMID- 25060076
TI  - Accommodating pregnant emergency physicians.

PMID- 25060078
TI  - Coming of age: emergency point of care ultrasonography in Canada.

PMID- 25060080
TI  - Teaching the RAPID approach at the start of emergency medicine clerkship: an
      evaluation.
AB  - BACKGROUND: The RAPID approach (Resuscitation, Analgesia and assessment, Patient
      needs, Interventions, Disposition) was developed as an approach to managing
      emergency department patients. It is a mental checklist to help trainees provide
      comprehensive care, addressing issues in priority. Its impact on trainee
      performance has not been assessed. METHODS: Forty-two clerkship students were
      enrolled, with 21 students in each group. They received or did not receive the
      teaching intervention on an alternate basis. Students were assessed through daily
      encounter cards, a case presentation, a self-assessment form, a prerotation case
      (case E), and a six-case short-answer exit examination (cases A to F) with case E
      repeated. Case E was designed specifically to assess students' ability to provide
      comprehensive care. Fourteen students participated in focus groups. RESULTS:
      Students in the intervention group had significantly higher exit examination case
      E scores (11.67 of 14 v. 10.26 of 14, p  =  0.008) and improvement in their case
      E scores from pre- to postrotation (1.82 v. 0.26, p  =  0.006). There were no
      significant differences in the other outcome measures. Intervention group
      students made positive comments around analgesia, addressing nonmedical needs and
      counseling on health promotion during focus groups. CONCLUSIONS: Students exposed
      to the RAPID approach at the start of their emergency medicine rotation performed
      better on the one component of the written examination for which it was designed
      to improve performance. Students found it to be a useful mental checklist for
      comprehensive care, possibly addressing the hidden curriculum. Emergency medicine
      educators should consider further study and careful implementation of the RAPID
      approach.

PMID- 25060081
TI  - Variation in the use of skull radiographs by emergency physicians in young
      children with minor head trauma.
AB  - BACKGROUND: Minor head trauma in young children is a major cause of emergency
      department visits. Conflicting guidelines exist regarding radiologic evaluation
      in such cases. OBJECTIVE: To determine the practice pattern among Canadian
      emergency physicians for ordering skull radiographs in young children suffering
      from minor head trauma. Physicians were also surveyed on their willingness to use
      a clinical decision rule in such cases. DESIGN/METHODS: A self-administered email
      questionnaire was sent to all members of the Pediatric Emergency Research Canada
      (PERC) group. It consisted of clinical vignettes followed by multiple-option
      answers on the management plan. The study was conducted using the principles of
      the Dillman Tailored Design method and included multiple emailings to maximize
      the response rate. The research protocol received Institutional Review Board
      approval. RESULTS: A total of 158 of 295 (54%) PERC members responded. Most
      participants were trained in pediatric emergency medicine and assessed more than
      500 children per year. Imaging management for the vignettes was highly variable:
      6 of the 11 case scenarios had a proportion of radiograph ordering between 20 and
      80%. Ninety-five percent of respondents stated that they would apply a validated
      clinical decision rule for the detection of skull fracture in young children with
      minor head trauma. The minimum sensitivity deemed acceptable for such a rule was
      98%. CONCLUSION: Canadian emergency physicians have a wide variation in skull
      radiography ordering in young children with minor head trauma. This variation,
      along with the need expressed by physicians, suggests that further research to
      develop a clinical decision rule is warranted.

PMID- 25060082
TI  - Socioeconomic status and the use of computed tomography in the emergency
      department.
AB  - BACKGROUND: Low socioeconomic status (SES) is associated with adverse health
      outcomes. Possible explanations include differences in health status, access to
      health care, and care provided by clinicians. We sought to determine whether SES
      is associated with computed tomography (CT) use in the emergency department (ED).
      METHODS: A retrospective cohort study of all Ontario ED patients (April 1, 2009,
      to March 31, 2010) using administrative databases was conducted, and patients
      were stratified into SES quintiles based on median neighbourhood income. Using
      multivariate logistical regression, CT scan use within SES quintiles was compared
      for all patients and subgroups based on chief complaints: headache, abdominal
      pain, and complex abdominal pain (age >= 65 years, high acuity, and admittance to
      hospital). RESULTS: We analyzed 4,551,101 patient visits, of which 52% were
      female. Overall, 8.2% underwent CT scanning. In adjusted analyses, the lowest SES
      patients were less likely to undergo CT scanning overall and in all clinical
      subgroups, except for complex abdominal pain. Compared to the lowest SES
      quintile, the adjusted odds ratios of CT scanning in the highest SES quintile
      were 1.08 (95% CI 1.07-1.09), 1.28 (95% CI 1.22-1.34), and 1.24 (95% CI 1.21
      1.27) for all patients, headache pain patients, and abdominal pain patients,
      respectively. For patients presenting with complex abdominal pain, no significant
      difference in CT use was observed. CONCLUSION: Lowest SES ED patients were less
      likely to receive CT scans overall and in headache and abdominal pain subgroups.
      No difference was seen among complex abdominal pain patients, suggesting that as
      clinical indications for the test become more clearcut, use across SES quintiles
      differs less.

PMID- 25060083
TI  - Diagnosis of occult scaphoid fractures: a randomized, controlled trial comparing
      bone scans to radiographs for diagnosis.
AB  - BACKGROUND: Many patients with suspected scaphoid fractures but negative
      radiographs are immobilized for >= 2 weeks and are eventually found to have no
      fracture. Bone scans are reportedly 99% sensitive for these injuries if done >=
      72 hours postinjury. OBJECTIVE: The purpose of this study was to determine if
      early bone scans would allow for shorter cast immobilization periods in patients
      with suspected scaphoid fractures. METHODS: Twenty-seven patients with clinically
      suspected scaphoid fractures and negative radiographs were randomized to early
      diagnosis (bone scan within 3-5 days; n  =  12) or traditional diagnosis
      (radiographs 10-14 days postinjury; n  =  15). The primary outcome was number of
      days immobilized in a cast. RESULTS: The mean number of days immobilized was 26
      in the traditional group and 29 in the bone scan group. Overall, 6 patients had
      scaphoid fractures (2 in the traditional diagnosis group and 4 in the bone scan
      group; p > 0.05), and 8 had other types of fractures. These other types of
      fractures included four distal radius fractures, two triquetral fractures, one
      trapezoid fracture, and one hamate fracture. There was no significant difference
      in the number of other types of fractures between groups. The Kaplan-Meier
      survival analysis using the log-rank test revealed that there was no
      statistically significant difference between days immobilized between the
      radiograph and bone scan groups (p  =  0.38). CONCLUSIONS: The current study
      suggests that the use of bone scans to help diagnose occult scaphoid fractures
      does not reduce the number of days immobilized and that the differential
      diagnosis of occult scaphoid fractures should remain broad because other injuries
      are common.

PMID- 25060084
TI  - Quality assurance evaluation of a simple linear protocol for the treatment of
      impending status epilepticus in a pediatric emergency department 2 years
      postimplementation.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a simple linear midazolam-based
      protocol for the management of impending status epilepticus in children up to 18
      years of age. METHODS: This is a descriptive, quality assessment, retrospective
      chart review of children presenting with the chief complaint of seizure disorder
      in the emergency department (ED) of a tertiary care pediatric hospital and a
      triage category of resuscitation or urgent from April 1, 2009, to August 31,
      2011. In children with at least one seizure episode in the ED treated according
      to the linear protocol, three main outcomes were assessed: compliance,
      effectiveness, and complications. RESULTS: Of the 128 children meeting the above
      study criteria, 68 had at least one seizure episode in the ED, and treatment was
      required to terminate at least one seizure episode in 46 of 68 patients (67.6%).
      Fifty-five seizure episodes were treated in the 46 patients: 51 of 55 seizure
      episodes were treated with midazolam (92.7%) and 4 of 55 with lorazepam or
      diazepam (7.3%). Of those treated with midazolam, 86.3% (44 of 51) were
      successfully treated with one or two doses of midazolam. The median seizure
      duration for all treated patients was 6 minutes. Of the 42 patients treated with
      midazolam, 7 required either continuous positive airway pressure or intubation,
      and two patients were treated for hypotension. One patient died of pneumococcal
      meningitis. CONCLUSION: This simple linear protocol is an effective and safe
      regimen for the treatment of impending status epilepticus in children.

PMID- 25060085
TI  - Drowning: an overlooked cause of out-of-hospital cardiac arrest in Canada.
AB  - INTRODUCTION: Drowning is a major public health concern, yet little is known
      about the characteristics of drowning patients. The objectives of this study were
      to describe the demographic and clinical characteristics of out-of-hospital
      cardiac arrest (OHCA) attributed to drowning in Ontario and to compare the
      characteristics of OHCA attributed to drowning to those of presumed cardiac
      etiology. METHODS: A retrospective, observational study was carried out of
      consecutive OHCA patients of drowning etiology in Ontario between August 2006 and
      July 2011. Bivariate analysis was used to evaluate differences between drowning
      and presumed cardiac etiologies. RESULTS: A total of 31,763 OHCA patients were
      identified, and 132 (0.42%) were attributed to drowning. Emergency medical
      services treated 98 patients, whereas the remaining 34 met the criteria for
      legislative death. Overall, 5.1% of drowning patients survived to hospital
      discharge. When compared to patients of presumed cardiac etiology, drowning
      patients were younger and their arrest was more likely to be unwitnessed, present
      with a nonshockable initial rhythm, occur in a public location, and receive
      bystander cardiopulmonary resuscitation (CPR). A nonsignificant trend was noted
      for drowning cases to more frequently have a public access AED applied. There
      were no significant differences in the gender ratio or paramedic response times.
      Drowning patients were more likely to be transported to hospital but had a trend
      to be less likely to arrive with a return of spontaneous circulation. They were
      also more likely to be admitted to hospital but had no difference in survival to
      hospital discharge. CONCLUSIONS: Significant differences exist between OHCA of
      drowning and presumed cardiac etiologies. Most drownings are unwitnessed, occur
      in public locations, and present with nonshockable initial rhythms, suggesting
      that treatment should focus on bystander CPR. Future initiatives should focus on
      strategies to improve supervision in targeted locations and greater emphasis on
      bystander-initiated CPR, both of which may reduce drowning mortality.

PMID- 25060086
TI  - How to diagnose a Canadian: a case of foreign body ingestion.

PMID- 25060087
TI  - Is it more accurate to measure the absolute or the relative change of new high or
      ultrasensitive troponin assays to diagnose acute myocardial infarction?
AB  - CLINICAL QUESTION: In emergency department patients with symptoms suggestive of
      acute myocardial infarction, is the absolute or relative change of cardiac
      troponin assays (either high sensitivity or ultrasenstive) more accurate in
      diagnosing acute myocardial infarction at 1 to 2 hours postpresentation? ARTICLE
      CHOSEN: Rechlin T, Ifran A, Twerenbold R, et al. Utility of absolute and relative
      changes in cardiac troponin concentrations in the early diagnosis of acute
      myocardial infarction. Circulation 2011;124:136-45. OBJECTIVE: To evaluate the
      accuracy of new troponin assays in diagnosing acute myocardial events.

PMID- 25060088
TI  - Traumatic intracranial hemorrhage in patients using warfarin or clopidogrel.
AB  - CLINICAL QUESTION: What is the prevalence of immediate and incidence of delayed
      intracranial hemorrhage in patients with blunt head trauma who use warfarin or
      clopidogrel? ARTICLE CHOSEN: Nishijima DK, Offerman SR, Ballard DW, et al.
      Immediate and delayed traumatic intracranial hemorrhage in patients with head
      trauma and preinjury warfarin or clopidogrel use. Ann Emerg Med 2012;59:460-8.e7.
      STUDY OBJECTIVE: To assess the prevalence of immediate and the cumulative
      incidence of delayed traumatic intracranial hemorrhage in patients using warfarin
      or clopidogrel.

PMID- 25060089
TI  - Unnecessary shock from an implantable cardioverter-defibrillator following
      transcutaneous pacing.
AB  - As the population ages and cardiovascular disease becomes more prevalent, an
      increasing number of patients are receiving implantable cardioverter
      defibrillators (ICDs). When these patients present to the emergency department,
      it is imperative that physicians are not only aware of the possible underlying
      medical issues that may have precipitated their admission but should also have a
      good understanding of the potential interactions that any medical intervention
      may have on the patient's device. We discuss a case in which a patient known to
      have an ICD in situ was transcutaneously paced for the management of bradycardia,
      leading to an unnecessary shock.

PMID- 25060090
TI  - Holocord spinal epidural abscess in a pregnant patient presenting as premature
      labour: a rare presentation of an unusual diagnosis.
AB  - Spinal epidural abscess (SEA) is a rare clinical entity. It is less common when
      the entire epidural space is involved, known as a holocord or panspinal SEA, and
      it is even less common in a pregnant patient. We report a case of methicillin
      resistant Staphylococcus aureus holocord SEA in a 30-year-old female at
      approximately 22 weeks' gestational age who presented with lumbar pain and pelvic
      pressure and the urge to bear down. Magnetic resonance imaging of the spine
      demonstrated extensive SEA and meningitis from the foramen magnum to the lumbar
      spine that was treated both medically and surgically. The incidence of, clinical
      presentation of, and risk factors for developing SEA are discussed. If untreated,
      expanding SEAs produce sensory symptoms and signs, motor dysfunction, and,
      eventually, paralysis and death. The medical and surgical management of SEA is
      also discussed. SEA can have an insidious and atypical presentation despite
      extensive involvement of the epidural space. Therefore, the diagnosis of SEA
      should always be considered in patients who present to the emergency department
      with back pain.

PMID- 25060091
TI  - Streptococcus pneumoniae-induced purpura fulminans in a woman with functional
      asplenia.
AB  - Purpura fulminans is a rare complication of septic shock, often associated with
      Streptococcus pneumoniae. Patients with anatomic or functional asplenia are at
      increased risk for infection because of impairment of their ability to defend
      against encapsulated pathogens. We report the case of a previously healthy,
      unimmunized 33-year-old female with functional asplenia who presented in septic
      shock and purpura fulminans and died in spite of maximal resuscitative measures.
      The clinical presentation, diagnosis, and management of purpura fulminans are
      reviewed. Purpura fulminans is a rare condition that requires early diagnosis and
      aggressive management by emergency physicians.

PMID- 25060093
TI  - Photodynamics of a Proton-Transfer Dye in Solutions and Confined Within NaX and
      NaY Zeolites.
AB  - We report on steady-state, picosecond and femtosecond time-resolved emission
      studies of 2-(2'-hydroxyphenyl)benzoxazole (HBO) in solutions and interacting
      with NaX and NaY zeolites. In solutions, an ultrafast (less than 150 fs) excited
      state intramolecular proton-transfer (ESIPT) reaction takes place in syn-enol
      form, and leads to keto-type tautomer. We also observed a torsional motion in the
      keto form (~20 ps in dichloromethane, DCM). For NaX and NaY DCM suspensions,
      anionic forms interacting with the zeolites at S0 and S1 states are generated.
      They show two fluorescence lifetimes in both zeolites (720 ps and 2.4 ns for NaY
      and 960 ps and 2.7 ns for NaX), while those of the enol bonded to the zeolite
      framework and of the free keto forms are ~100 and 250 ps, respectively. The
      ultrafast dynamics of the anion in alkaline solutions reveals two deactivation
      pathways: an intramolecular charge transfer (ICT, 1.2 ps) and a twisting motion,
      affected by the viscosity of the solvent (12 and 20 ps for MeOH and ethylene
      glycol). When HBO is interacting with NaX and NaY the twisting motion is
      cancelled, while the ICT becomes slower as a result of a combination of several
      environment effects. HBO anions within the faujasite framework show also a ~ 30
      ps decay associated to a non-fluorescent (n, pi*) state. Our results demonstrate
      how intermolecular H-bonds, the confinement and the electrostatic interactions of
      HBO with the used materials, affect its ground as well as its excited state
      properties. Our findings add new knowledge on the interactions of silica-based
      nanomaterials containing the H-bonding guests.

PMID- 25060092
TI  - Met1-linked ubiquitination in immune signalling.
AB  - N-terminal methionine-linked ubiquitin (Met1-Ub), or linear ubiquitin, has
      emerged as a central post-translational modification in innate immune signalling.
      The molecular machinery that assembles, senses and, more recently, disassembles
      Met1-Ub has been identified, and technical advances have enabled the
      identification of physiological substrates for Met1-Ub in response to activation
      of innate immune receptors. These discoveries have significantly advanced our
      understanding of how nondegradative ubiquitin modifications control
      proinflammatory responses mediated by nuclear factor-kappaB and mitogen-activated
      protein kinases. In this review, we discuss the current data on Met1-Ub function
      and regulation, and point to some of the questions that still remain unanswered. 

PMID- 25060094
TI  - Quantitative study of protein-protein interactions by quartz nanopipettes.
AB  - In this report, protein-modified quartz nanopipettes were used to quantitatively
      study protein-protein interactions in attoliter sensing volumes. As shown by
      numerical simulations, the ionic current through the conical-shaped nanopipette
      is very sensitive to the surface charge variation near the pore mouth. With the
      appropriate modification of negatively charged human neuroglobin (hNgb) onto the
      inner surface of a nanopipette, we were able to detect concentration-dependent
      current change when the hNgb-modified nanopipette tip was exposed to positively
      charged cytochrome c (Cyt c) with a series of concentrations in the bath
      solution. Such current change is due to the adsorption of Cyt c to the inner
      surface of the nanopipette through specific interactions with hNgb. In contrast,
      a smaller current change with weak concentration dependence was observed when Cyt
      c was replaced with lysozyme, which does not specifically bind to hNgb. The
      equilibrium dissociation constant (KD) for the Cyt c-hNgb complex formation was
      derived and the value matched very well with the result from surface plasmon
      resonance measurement. This is the first quantitative study of protein-protein
      interactions by a conical-shaped nanopore based on charge sensing. Our results
      demonstrate that nanopipettes can potentially be used as a label-free analytical
      tool to quantitatively characterize protein-protein interactions. 

PMID- 25060095
TI  - Global motion perception deficits in autism are reflected as early as primary
      visual cortex.
AB  - Individuals with autism are often characterized as 'seeing the trees, but not the
      forest'-attuned to individual details in the visual world at the expense of the
      global percept they compose. Here, we tested the extent to which global
      processing deficits in autism reflect impairments in (i) primary visual
      processing; or (ii) decision-formation, using an archetypal example of global
      perception, coherent motion perception. In an event-related functional MRI
      experiment, 43 intelligence quotient and age-matched male participants (21 with
      autism, age range 15-27 years) performed a series of coherent motion perception
      judgements in which the amount of local motion signals available to be integrated
      into a global percept was varied by controlling stimulus viewing duration (0.2 or
      0.6 s) and the proportion of dots moving in the correct direction (coherence: 4%,
      15%, 30%, 50%, or 75%). Both typical participants and those with autism evidenced
      the same basic pattern of accuracy in judging the direction of motion, with
      performance decreasing with reduced coherence and shorter viewing durations.
      Critically, these effects were exaggerated in autism: despite equal performance
      at the long duration, performance was more strongly reduced by shortening viewing
      duration in autism (P < 0.015) and decreasing stimulus coherence (P < 0.008). To
      assess the neural correlates of these effects we focused on the responses of
      primary visual cortex and the middle temporal area, critical in the early visual
      processing of motion signals, as well as a region in the intraparietal sulcus
      thought to be involved in perceptual decision-making. The behavioural results
      were mirrored in both primary visual cortex and the middle temporal area, with a
      greater reduction in response at short, compared with long, viewing durations in
      autism compared with controls (both P < 0.018). In contrast, there was no
      difference between the groups in the intraparietal sulcus (P > 0.574). These
      findings suggest that reduced global motion perception in autism is driven by an
      atypical response early in visual processing and may reflect a fundamental
      perturbation in neural circuitry.

PMID- 25060097
TI  - Intrathecal somatic hypermutation of IgM in multiple sclerosis and
      neuroinflammation.
AB  - Intrathecal oligoclonal bands of the cerebrospinal fluid are considered the most
      important immunological biomarkers of multiple sclerosis. They typically consist
      of clonally expanded IgG antibodies that underwent affinity maturation during
      sustained stimulation by largely unknown antigens. In addition, ~40% of patients
      with multiple sclerosis have oligoclonal bands that consist of expanded IgM
      antibodies. We investigated the molecular composition of IgM- and IgG-chains from
      cerebrospinal fluid of 12 patients with multiple sclerosis, seven patients with
      other neurological diseases, and eight healthy control subjects by high
      throughput deep-sequencing and single-cell PCR. Further, we studied the
      expression of activation-induced cytidine deaminase, the key enzyme for affinity
      maturation of antibodies, in cerebrospinal fluid samples of 16 patients. From the
      cerebrospinal fluid of two multiple sclerosis patients we isolated single B cells
      and investigated the co-expression of antibody chains with activation-induced
      cytidine deaminase. In striking contrast to IgM-chains from peripheral blood, IgM
      chains from cerebrospinal fluid of patients with multiple sclerosis or
      neuroborreliosis showed a high degree of somatic hypermutation. We found a high
      content of mutations that caused amino acid exchanges as compared to silent
      mutations. In addition, more mutations were found in the complementarity
      determining regions of the IgM-chains, which interact with yet unknown antigens,
      as compared to framework regions. Both observations provide evidence for antigen
      driven affinity maturation. Furthermore, single B cells from the cerebrospinal
      fluid of patients with multiple sclerosis co-expressed somatically hypermutated
      IgM-chains and activation-induced cytidine deaminase, an enzyme that is crucial
      for somatic hypermutation and class switch recombination of antibodies and is
      normally expressed during activation of B cells in germinal centres. Clonal
      tracking of particular IgM(+) B cells allowed us to relate unmutated ancestor
      clones in blood to hypermutated offspring clones in CSF. Unexpectedly, however,
      we found no evidence for intrathecal isotype switching from IgM to IgG. Our data
      suggest that the intrathecal milieu sustains a germinal centre-like reaction with
      clonal expansion and extensive accumulation of somatic hypermutation in IgM
      producing B cells.

PMID- 25060098
TI  - Association between a single nucleotide polymorphism in the TP53 region and risk
      of ovarian cancer.
AB  - TP53 is known as a tumor suppressor gene involved in cell cycle regulation. Many
      previous epidemiological and clinical studies have evaluated the effects of
      rs1042522 polymorphism on risk of ovarian cancer. But the results are conflicting
      and heterogeneous. The primary objective of this study was to examine whether
      rs1042522 polymorphism is associated with ovarian cancer risk. We performed a
      comprehensive meta-analysis of 19 case-control studies that analyzed rs1042522
      polymorphism in ovarian cancer risk. Odds ratios (ORs) were calculated using
      distinct genetic models. Heterogeneity between studies was detected by the chi(2)
      based Q test. Additional analyses such as sensitivity analyses and publication
      bias were also performed. The rs1042522 polymorphism was not overall associated
      with ovarian cancer risk. But there was a borderline association in the
      heterozygote model (OR = 1.09, 95 % CI 0.99-1.21). Similar effects were observed
      in the subgroup of Caucasian population (the heterozygote model: OR = 1.11, 95 %
      CI 1.00-1.24). No significant heterogeneity and publication bias were revealed in
      this meta-analysis. This study provides statistical evidence that TP53 rs1042522
      polymorphism may play a role in modulating risk of ovarian cancer. This
      observation requires further analysis of a larger study size.

PMID- 25060099
TI  - In silico analysis of miRNA-mediated gene regulation in OCA and OA genes.
AB  - Albinism is an autosomal recessive genetic disorder due to low secretion of
      melanin. The oculocutaneous albinism (OCA) and ocular albinism (OA) genes are
      responsible for melanin production and also act as a potential targets for
      miRNAs. The role of miRNA is to inhibit the protein synthesis partially or
      completely by binding with the 3'UTR of the mRNA thus regulating gene expression.
      In this analysis, we predicted the genetic variation that occurred in 3'UTR of
      the transcript which can be a reason for low melanin production thus causing
      albinism. The single nucleotide polymorphisms (SNPs) in 3'UTR cause more new
      binding sites for miRNA which binds with mRNA which leads to inhibit the
      translation process either partially or completely. The SNPs in the mRNA of OCA
      and OA genes can create new binding sites for miRNA which may control the gene
      expression and lead to hypopigmentation. We have developed a computational
      procedure to determine the SNPs in the 3'UTR region of mRNA of OCA (TYR, OCA2,
      TYRP1 and SLC45A2) and OA (GPR143) genes which will be a potential cause for
      albinism. We identified 37 SNPs in five genes that are predicted to create 87 new
      binding sites on mRNA, which may lead to abrogation of the translation process.
      Expression analysis confirms that these genes are highly expressed in skin and
      eye regions. It is well supported by enrichment analysis that these genes are
      mainly involved in eye pigmentation and melanin biosynthesis process. The network
      analysis also shows how the genes are interacting and expressing in a complex
      network. This insight provides clue to wet-lab researches to understand the
      expression pattern of OCA and OA genes and binding phenomenon of mRNA and miRNA
      upon mutation, which is responsible for inhibition of translation process at
      genomic levels.

PMID- 25060100
TI  - Soft selective sweeps in complex demographic scenarios.
AB  - Adaptation from de novo mutation can produce so-called soft selective sweeps,
      where adaptive alleles of independent mutational origin sweep through the
      population at the same time. Population genetic theory predicts that such soft
      sweeps should be likely if the product of the population size and the mutation
      rate toward the adaptive allele is sufficiently large, such that multiple
      adaptive mutations can establish before one has reached fixation; however, it
      remains unclear how demographic processes affect the probability of observing
      soft sweeps. Here we extend the theory of soft selective sweeps to realistic
      demographic scenarios that allow for changes in population size over time. We
      first show that population bottlenecks can lead to the removal of all but one
      adaptive lineage from an initially soft selective sweep. The parameter regime
      under which such "hardening" of soft selective sweeps is likely is determined by
      a simple heuristic condition. We further develop a generalized analytical
      framework, based on an extension of the coalescent process, for calculating the
      probability of soft sweeps under arbitrary demographic scenarios. Two important
      limits emerge within this analytical framework: In the limit where population
      size fluctuations are fast compared to the duration of the sweep, the likelihood
      of soft sweeps is determined by the harmonic mean of the variance effective
      population size estimated over the duration of the sweep; in the opposing slow
      fluctuation limit, the likelihood of soft sweeps is determined by the
      instantaneous variance effective population size at the onset of the sweep. We
      show that as a consequence of this finding the probability of observing soft
      sweeps becomes a function of the strength of selection. Specifically, in species
      with sharply fluctuating population size, strong selection is more likely to
      produce soft sweeps than weak selection. Our results highlight the importance of
      accurate demographic estimates over short evolutionary timescales for
      understanding the population genetics of adaptation from de novo mutation. 

PMID- 25060102
TI  - Melatonin: a well-documented antioxidant with conditional pro-oxidant actions.
AB  - Melatonin (N-acetyl-5-methoxytryptamine), an indoleamine produced in many organs
      including the pineal gland, was initially characterized as a hormone primarily
      involved in circadian regulation of physiological and neuroendocrine function.
      Subsequent studies found that melatonin and its metabolic derivatives possess
      strong free radical scavenging properties. These metabolites are potent
      antioxidants against both ROS (reactive oxygen species) and RNS (reactive
      nitrogen species). The mechanisms by which melatonin and its metabolites protect
      against free radicals and oxidative stress include direct scavenging of radicals
      and radical products, induction of the expression of antioxidant enzymes,
      reduction of the activation of pro-oxidant enzymes, and maintenance of
      mitochondrial homeostasis. In both in vitro and in vivo studies, melatonin has
      been shown to reduce oxidative damage to lipids, proteins and DNA under a very
      wide set of conditions where toxic derivatives of oxygen are known to be
      produced. Although the vast majority of studies proved the antioxidant capacity
      of melatonin and its derivatives, a few studies using cultured cells found that
      melatonin promoted the generation of ROS at pharmacological concentrations (MUm
      to mm range) in several tumor and nontumor cells; thus, melatonin functioned as a
      conditional pro-oxidant. Mechanistically, melatonin may stimulate ROS production
      through its interaction with calmodulin. Also, melatonin may interact with
      mitochondrial complex III or mitochondrial transition pore to promote ROS
      production. Whether melatonin functions as a pro-oxidant under in vivo conditions
      is not well documented; thus, whether the reported in vitro pro-oxidant actions
      come into play in live organisms remains to be established. 

PMID- 25060101
TI  - Shared genetic pathways contribute to the tolerance of endogenous and low-dose
      exogenous DNA damage in yeast.
AB  - DNA damage that escapes repair and blocks replicative DNA polymerases is
      tolerated by bypass mechanisms that fall into two general categories: error-free
      template switching and error-prone translesion synthesis. Prior studies of DNA
      damage responses in Saccharomyces cerevisiae have demonstrated that repair
      mechanisms are critical for survival when a single, high dose of DNA damage is
      delivered, while bypass/tolerance mechanisms are more important for survival when
      the damage level is low and continuous (acute and chronic damage, respectively).
      In the current study, epistatic interactions between DNA-damage tolerance genes
      were examined and compared when haploid yeast cells were exposed to either
      chronic ultraviolet light or chronic methyl methanesulfonate. Results demonstrate
      that genes assigned to error-free and error-prone bypass pathways similarly
      promote survival in the presence of each type of chronic damage. In addition to
      using defined sources of chronic damage, rates of spontaneous mutations generated
      by the Pol zeta translesion synthesis DNA polymerase (complex insertions in a
      frameshift-reversion assay) were used to infer epistatic interactions between the
      same genes. Similar epistatic interactions were observed in analyses of
      spontaneous mutation rates, suggesting that chronic DNA-damage responses
      accurately reflect those used to tolerate spontaneous lesions. These results have
      important implications when considering what constitutes a safe and acceptable
      level of exogenous DNA damage. 

PMID- 25060103
TI  - [Effectiveness of forgiveness therapy on resilience, self-esteem, and
      spirituality of wives of alcoholics].
AB  - PURPOSE: In this study the effects of forgiveness therapy on the resilience, self
      esteem, and spirituality of wives of men suffering from alcohol abuse was
      examined. METHODS: The study design was a quasi-experimental design. Forgiveness
      therapy was conducted once a week for 12 weeks. Data were obtained from March
      2012 to December 2013. Participants were chosen from women in two Alcohol
      Counseling Centers. Of the 29 participants, 16 were assigned to the experimental
      group and 13 to the control group. Data were analyzed using descriptive
      statistics, t-test, chi(2)-test, and repeated measure ANOVA. RESULTS: There were
      statistically significantly differences for resilience, self-esteem, and
      spirituality between the experimental and control groups. Forgiveness therapy
      improved the resilience, self-esteem, and spirituality in the experimental group
      compared to the control group (p<.05). In follow-up tests, the experimental group
      had a statistically significantly increase only in self-esteem. CONCLUSION: This
      study results show that forgiveness therapy is effective in improving resilience,
      self-esteem, and spirituality in wives of men suffering from alcohol abuse.
      Therefore, forgiveness therapy can be considered a useful nursing intervention to
      promote improvements in emotional stability and provide pain relief for these
      wives.

PMID- 25060104
TI  - [Development of reproductive health program and identification of effect for
      married women immigrants].
AB  - PURPOSE: This study was done to develop a reproductive health program to improve
      reproductive health of women immigrants. METHODS: The participants in the study
      were 58 immigrant women who lived in Vietnam, China, Philippines, or Cambodia
      before marriage. They were assigned to the experiment group (n=29) or the control
      group (n=29). The reproductive health program for this study consisted of
      reproductive health education, health counseling, phone monitoring, and emotional
      support based on Cox (1982)'s Interaction Model of Client Health Behavior and was
      implemented for four weeks. RESULTS: There were significant differences in
      reproductive health knowledge (t=9.78, p<.001), reproductive health attitude
      (t=6.59, p<.001), and reproductive health behavior (t=5.11, p<.001) within and
      between groups after the reproductive health program. But there were no
      significant differences in clinical indicators between the two groups.
      CONCLUSION: The results of this study indicate the that reproductive health
      program for the women immigrants is effective in terms of reproductive health
      knowledge, reproductive health attitude and reproductive health behaviors.
      Therefore, nurses in public and private facilities, such as multicultural centers
      and public health centers in each community, should develop strategies to expand
      and provide reproductive health programs for women immigrants.

PMID- 25060105
TI  - [Structural equation modeling on burnout in clinical nurses based on CS-CF
      model].
AB  - PURPOSE: The purpose of this study was to construct and test a structural
      equation modeling on burnout of clinical nurses based on CS-CF model. METHODS: A
      survey using a structured questionnaire was conducted with 557 clinical nurses.
      Data were analyzed using structural equation modeling. RESULTS: The modified
      hypothetical model yielded the following chi(2)=289.70, p<.001, RMSEA=.09,
      GFI=.93, TLI=.91, CFI=.94, PCFI=.65, AIC=363.21, SRMR=.05 or less and showed good
      fit indices. Nursing work environment, patient safety culture and resilience
      showed indirect effects on burnout while compassion fatigue and compassion
      satisfaction had direct effects. CONCLUSION: Results of this study suggest that
      compassion fatigue must be decreased and compassion satisfaction has to be
      increased, while burnout is lowered by enhancing the clinical nursing work
      environment, patient safety culture and resilience. In addition, more variables
      and longitudinal studies are necessary to validate the clear cause-and-effect
      relationship between the relevant variables.

PMID- 25060106
TI  - [Sleep disorder experience in older patients with depression].
AB  - PURPOSE: The purpose of this study was to identify sleep disorder experience in
      older patients living in the community and acknowledging being depressed.
      METHODS: For this study, 11 older patients with depression were purposively
      chosen. Data were collected through in-depth individual interviews from July 2013
      to January 2014 and analyzed in terms of by Giorgi's phenomenological
      methodology. RESULTS: The study results showed that sleep disorder experience in
      older patients with depression consisted of sixteen themes and five themes
      clusters: 1) exposure of the causes of sleep disorders; 2) life is painful; 3)
      harassing themselves and their family; 4) difficulty in controlling themselves;
      5) trying to deal with the sleep disorder to overcome the situation. CONCLUSION:
      It is necessary to develop educational guidelines for patients with sleep
      disorders or nursing interventions that anyone can easily provide for elders in
      the communities. The first priority should be given to efforts to apply diverse
      methods to improve sleep hygiene and minimize the period of exposure to
      medication before starting medication for patients with sleep disorders.

PMID- 25060107
TI  - [Development and evaluation of an enteral nutrition protocol for dysphagia in
      patients with acute stroke].
AB  - PURPOSE: The study was done to develop an evidence-based enteral nutrition (EN)
      protocol for effective nutritional support for dysphagia in patients with acute
      stroke, and to evaluate effects of this protocol on clinical outcomes. METHODS: A
      methodological study was used to develop the EN protocol and a quasi-experimental
      study to verify the effectiveness of the protocol. The preliminary EN protocol
      was drawn by selecting recommendations from previous well-designed EN guidelines,
      and then developing additional recommendations based on high-quality evidence.
      Content validation was assessed by an expert group, and clinical applicability by
      care providers and patients. The scale-level content validity index of the final
      EN protocol was 0.99. Assessment was done of differences in percentage of caloric
      goals achieved and presence of undernutrition, aspiration pneumonia, and
      gastrointestinal (GI) complications after application of the EN protocol.
      RESULTS: In the EN protocol group, the percentage of caloric goals achieved
      (R(2)=.24, p=.001) and the reduction of GI complications (p=.045) were
      significantly improved, but the presence of undernutrition (p=.296) and
      aspiration pneumonia (p=.601) did not differ from the usual care group.
      CONCLUSION: Results indicate that the new EN protocol for dysphagia in patients
      with acute stroke significantly increased their nutritional intake and reduced GI
      complications.

PMID- 25060108
TI  - [Implementation of ontology-based clinical decision support system for management
      of interactions between antihypertensive drugs and diet].
AB  - PURPOSE: The influence of dietary composition on blood pressure is an important
      subject in healthcare. Interactions between antihypertensive drugs and diet
      (IBADD) is the most important factor in the management of hypertension. It is
      therefore essential to support healthcare providers' decision making role in
      active and continuous interaction control in hypertension management. The aim of
      this study was to implement an ontology-based clinical decision support system
      (CDSS) for IBADD management (IBADDM). We considered the concepts of
      antihypertensive drugs and foods, and focused on the interchangeability between
      the database and the CDSS when providing tailored information. METHODS: An
      ontology-based CDSS for IBADDM was implemented in eight phases: (1) determining
      the domain and scope of ontology, (2) reviewing existing ontology, (3) extracting
      and defining the concepts, (4) assigning relationships between concepts, (5)
      creating a conceptual map with CmapTools, (6) selecting upper ontology, (7)
      formally representing the ontology with Protege (ver.4.3), (8) implementing an
      ontology-based CDSS as a JAVA prototype application. RESULTS: We extracted 5,926
      concepts, 15 properties, and formally represented them using Protege. An ontology
      based CDSS for IBADDM was implemented and the evaluation score was 4.60 out of 5.
      CONCLUSION: We endeavored to map functions of a CDSS and implement an ontology
      based CDSS for IBADDM.

PMID- 25060109
TI  - [Role adaptation process of elementary school health teachers: establishing their
      own positions].
AB  - PURPOSE: The purpose of this study was to explore and identify patterns from the
      phenomenon of the role adaptation process in elementary school health teachers
      and finally, suggest a model to describe the process. METHODS: Grounded theory
      methodology and focus group interviews were used. Data were collected from 24
      participants of four focus groups. The questions used were about their experience
      of role adaptation including situational contexts and interactional coping
      strategies. Transcribed data and field notes were analyzed with continuous
      comparative analysis. RESULTS: The core category was 'establishing their own
      positions', an interactional coping strategy. The phenomenon identified by
      participants was confusion and wandering in their role performance. Influencing
      contexts were unclear beliefs for their role as health teachers and non
      supportive job environments. The result of the adaptation process was
      consolidation of their positions. Pride as health teachers and social recognition
      and supports intervened to produce that result. The process had three stages;
      entry, growth, and maturity. CONCLUSION: The role adaptation process of
      elementary school health teachers can be explained as establishing, strengthening
      and consolidating their own positions. Results of this study can be used as
      fundamental information for developing programs to support the role adaptation of
      health teachers.

PMID- 25060110
TI  - [Comparison of boys' and girls' families for actor and partner effect of stress,
      depression and parent-adolescent communication on middle school students'
      suicidal ideation: triadic data analysis].
AB  - PURPOSE: This study was done to compare families of boys or of girls for actor
      and partner effect of stress, depression and parent-adolescent communication as
      perceived by mother, father and adolescent on adolescents' suicidal ideation.
      METHODS: Participants were 183 families (104 boys' families, 79 girls' families)
      who met eligibility criteria. All measures were self-administered. Data were
      analyzed using SPSS 18.0 and AMOS 18.0 program. RESULTS: In boys' families, boys'
      depression and communication with father showed actor effect on boys' suicidal
      ideation. Boys' stress showed indirect effect on boys' suicidal ideation through
      communication with father and boys' depression. Mothers' depression showed
      indirect partner effect on boys' suicidal ideation through boys' depression. In
      families of girls, girls' depression and stress showed actor effects on girls'
      suicidal ideation. Girls' communication with mother showed indirect effects
      through girls' depression. Also girls' stress showed indirect effect through
      girls' depression. Stress in mothers and/or fathers showed partner effect on
      girls' suicidal ideation. CONCLUSION: To intervene in adolescents' suicidal
      ideation and promote adolescents' mental health, programs should be developed
      differently according to gender and based on parent's psychological states.

PMID- 25060111
TI  - [An analysis of cancer survival narratives using computerized text analysis
      program].
AB  - PURPOSE: This study was done to explore experiences of persons living through the
      periods of cancer diagnosis, treatment, and self-care. METHODS: With permission,
      texts of 29 cancer survival narratives (8 men and 21 women, winners in contests
      sponsored by two institutes), were analyzed using Kang's Korean-Computerized-Text
      Analysis-Program where the commonly used Korean-Morphological-Analyzer and the
      21st-century-Sejong-Modern-Korean-Corpora representing laymen's Korean-language
      use are connected. Experiences were explored based on words included in 100
      highly-used-morphemes. For interpretation, we used 'categorizing words by
      meaning', 'comparing use-rate by periods and to the 21st-century-Sejong-Modern
      Korean-Corpora', and highly-used-morphemes that appeared only in a specific
      period. RESULTS: The most highly-used-word-morpheme was first-person-pronouns
      followed by, diagnosis.treatment-related-words, mind-expression-words, cancer,
      persons-in-meaningful-interaction, living and eating, information-related-verbs,
      emotion-expression-words, with 240 to 0.8 times for layman use-rate. 'Diagnosis
      process', 'cancer-thought', 'things-to-come-after-diagnosis',
      'physician.husband', 'result-related-information', 'meaningful-things before
      diagnosis-period', and 'locus-of-cause' dominated the life of the diagnosis
      period. 'Treatment', 'unreliable-body', 'husband . people . mother . physician',
      'treatment-related-uncertainty', 'hard-time', and 'waiting-time represented
      experiences in the treatment-period. Themes of living in the self-care-period
      were complex and included 'living-as-a-human', 'self-managing-of-diseased-body',
      'positive-emotion', and 'connecting past . present . future'. CONCLUSION: The
      results show that the experience of living for persons with cancer is influenced
      by each period's own situational-characteristics. Experiences of the diagnosis
      and treatment-period are negative disease-oriented while that of the self-care
      period is positive present-oriented.

PMID- 25060112
TI  - [Development of a measurement of stress for hospitalized schizophrenic patient].
AB  - PURPOSE: This study was done to develop a measurement for stress experienced by
      patients with schizophrenia during hospitalization. METHODS: The preliminary tool
      was developed through in-depth interviews and a validity verification test of
      content. For data collection, 15 inpatients with schizophrenia were selected as
      participants for in-depth interviews and 195 patients admitted to one of eight
      psychiatric hospitals in four provinces were recruited as participants to test
      reliability and validity of the preliminary tool. RESULTS: The questionnaire was
      developed as a four-point Likert-type scale in a self-report form with 28 items.
      Factor analysis showed 28 items in six factors. Factors were named 'Unjust human
      rights infringement', 'Futureless life', 'Alienation from other family members',
      'Infringement of basic needs', 'Infringement of personal preference' and
      'Inconvenience of shared living'. The six factors explained 63.5% of the total
      variance. Cronbach's alpha for the total items was .93 and for the factors ranged
      from .65 to .87. CONCLUSION: A tool to measure stress in patients hospitalized
      with schizophrenic was developed based on identified hospitalization stress
      experiences. Study results indicate that this tool can be used to evaluate
      hospitalization stress in these patients and will contribute to establishing
      nursing interventions for relief of hospitalization stress.

PMID- 25060114
TI  - Amyloid transition of ubiquitin on silver nanoparticles produced by pulsed laser
      ablation in liquid as a function of stabilizer and single-point mutations.
AB  - The interaction of nanoparticles with proteins has emerged as a key issue in
      addressing the problem of nanotoxicity. We investigated the interaction of silver
      nanoparticles (AgNPs), produced by laser ablation with human ubiquitin (Ub), a
      protein essential for degradative processes in cells. The surface plasmon
      resonance peak of AgNPs indicates that Ub is rapidly adsorbed on the AgNP surface
      yielding a protein corona; the Ub-coated AgNPs then evolve into clusters held
      together by an amyloid form of the protein, as revealed by binding of thioflavin
      T fluorescent dye. Transthyretin, an inhibitor of amyloid-type aggregation,
      impedes aggregate formation and disrupts preformed AgNP clusters. In the presence
      of sodium citrate, a common stabilizer that confers an overall negative charge to
      the NPs, Ub is still adsorbed on the AgNP surface, but no clustering is observed.
      Ub mutants bearing a single mutation at one edge beta strand (i.e. Glu16Val) or
      in loop (Glu18Val) behave in a radically different manner. 

PMID- 25060113
TI  - Effects of an intervention aimed at reducing the intake of sugar-sweetened
      beverages in primary school children: a controlled trial.
AB  - BACKGROUND: Since sugar-sweetened beverages (SSB) may contribute to the
      development of overweight in children, effective interventions to reduce their
      consumption are needed. Here we evaluated the effect of a combined school- and
      community-based intervention aimed at reducing children's SSB consumption by
      promoting the intake of water. Favourable intervention effects on children's SSB
      consumption were hypothesized. METHODS: In 2011-2012, a controlled trial was
      conducted among four primary schools, comprising 1288 children aged 6-12 years
      who lived in multi-ethnic, socially deprived neighbourhoods in Rotterdam, the
      Netherlands. Intervention schools adopted the 'water campaign', an intervention
      developed using social marketing. Control schools continued with their regular
      health promotion programme. Primary outcome was children's SSB consumption,
      measured using parent and child questionnaires and through observations at
      school, both at baseline and after one year of intervention. RESULTS: Significant
      positive intervention effects were found for average SSB consumption (B -0.19
      litres, 95% CI -0.28;-0.10; parent report), average SSB servings (B -0.54
      servings, 95% CI -0.82;-0.26; parent report) and bringing SSB to school (OR 0.51,
      95% CI 0.36;0.72; observation report). CONCLUSIONS: This study supports the
      effectiveness of the water campaign intervention in reducing children's SSB
      consumption. Further studies are needed to replicate our findings. TRIAL
      REGISTRATION: Current Controlled Trials: NTR3400.

PMID- 25060115
TI  - Social cycling and conditional responses in the Rock-Paper-Scissors game.
AB  - How humans make decisions in non-cooperative strategic interactions is a big
      question. For the fundamental Rock-Paper-Scissors (RPS) model game system,
      classic Nash equilibrium (NE) theory predicts that players randomize completely
      their action choices to avoid being exploited, while evolutionary game theory of
      bounded rationality in general predicts persistent cyclic motions, especially in
      finite populations. However as empirical studies have been relatively sparse, it
      is still a controversial issue as to which theoretical framework is more
      appropriate to describe decision-making of human subjects. Here we observe
      population-level persistent cyclic motions in a laboratory experiment of the
      discrete-time iterated RPS game under the traditional random pairwise-matching
      protocol. This collective behavior contradicts with the NE theory but is
      quantitatively explained, without any adjustable parameter, by a microscopic
      model of win-lose-tie conditional response. Theoretical calculations suggest that
      if all players adopt the same optimized conditional response strategy, their
      accumulated payoff will be much higher than the reference value of the NE mixed
      strategy. Our work demonstrates the feasibility of understanding human
      competition behaviors from the angle of non-equilibrium statistical physics. 

PMID- 25060116
TI  - Intensification of enzymatic hydrolysis of waste newspaper using ultrasound for
      fermentable sugar production.
AB  - An effective conversion of lignocellulose into fermentable sugars is a key step
      in producing bioethanol in an eco-friendly and cost effective manner. In this
      study, the effect of ultrasound on enzymatic hydrolysis of newspaper, a potential
      feedstock for bioethanol production due to its high cellulosic content, was
      investigated. The effect of substrate loading, enzyme loading, temperature,
      ultrasonic power and duty cycle on the hydrolysis has been studied. Optimum
      conditions for conventional enzymatic hydrolysis were substrate loading of 5%
      (w/v), enzyme loading of 0.14% (w/v), temperature of 323K, and under these
      conditions and 72h of hydrolysis, reducing sugar yield of 11.569g/L was obtained.
      In case of ultrasound-assisted enzymatic hydrolysis approach, optimum conditions
      obtained were substrate loading of 3% (w/v), enzyme loading of 0.8% (w/v),
      sonication power of 60W, duty cycle of 70%, hydrolysis time of 6.5h and the
      reducing sugar yield obtained under these conditions was 27.6g/L. Approximately
      2.4 times increase in the release of reducing sugar concentration was obtained by
      the ultrasound-assisted enzymatic hydrolysis approach. Results indicate that
      there is a synergistic effect obtained from the combination of ultrasound and
      enzymes which lowers the diffusion-limiting barrier to enzyme/substrate binding
      and results in an increase in reaction rate. The experimental data were also
      fitted in a simple three parameter kinetic model. 

PMID- 25060117
TI  - Ultrasonics in isocyanide-based multicomponent reactions: a new, efficient and
      fast method for the synthesis of fully substituted 1,3,4-oxadiazole derivatives
      under ultrasound irradiation.
AB  - A fast and convenient approach to the synthesis of fully substituted 1,3,4
      oxadiazoles via three-component reaction of aromatic carboxylic acids,
      acenaphthoquinone, and (N-isocyanimino)triphenylphosphorane under ultrasound
      irradiation is described. Furthermore, a series of compounds were synthesized and
      characterized by melting point, IR, NMR and MS. Utilization of easy reaction
      conditions, very high to excellent yields, and short reaction times makes this
      manipulation potentially very useful. 

PMID- 25060118
TI  - Sonocatalytic removal of an organic dye using TiO2/Montmorillonite nanocomposite.
AB  - The sonocatalytic performance of the synthesized TiO2/Montmorillonite K10
      (TiO2/MMT) nanocomposite was studied in removal of Basic Blue 3 (BB3) from water.
      The TiO2/MMT nanocomposite was prepared by hydrothermal method. Scanning electron
      microscope, X-ray diffraction and Fourier transform infrared were used to
      characterize the synthesized nanocomposite. The average size of TiO2
      nanoparticles decreased from 60-80nm to 40-60nm through the immobilization of
      this semiconductor on the surface of MMT. The obtained results indicated that the
      sonocatalytic activity of TiO2/MMT nanocomposite was higher than that of pure
      TiO2 nanoparticles and MMT particles. Furthermore, the main influence factors on
      the sonocatalytic activity such as the BB3 concentration, pH of solution,
      TiO2/MMT dose, power of ultrasonic generator, and inorganic salts were studied.
      The intermediates of BB3 degradation during the sonocatalytic process in the
      presence of the TiO2/MMT nanocomposite have been monitored by gas chromatography
      mass spectrometry. 

PMID- 25060119
TI  - Effect of pH on the sonochemical synthesis of BiPO4 nanostructures and its
      electrochemical properties for pseudocapacitors.
AB  - Using sonochemical method, BiPO4 nanocrystals were prepared at different pH
      conditions (pH-1, 3, 5, 7, 9 & 12) for the possible applications of
      pseudocapacitor electrodes. The prepared BiPO4 nanocrystals belong to monoclinic
      structure with P21 space group. The SEM image revealed that the particles changed
      from irregular coarse shape into rod like structure (pH-1 to 7) which finally
      collapsed into irregular aggregates (pH-9 to pH-12). The observed spot patterns
      from SAED inferred the polycrystalline nature of the material. The
      electrochemical performance of the synthesized BiPO4 in various ultrasound
      irradiation conditions such as irradiation time (30min, 1h, 2h and 3h) and
      ultrasonication power (40%, 50%, 60% and 70% of instrumental power) was studied.
      A maximum specific capacitance of 1052F/g (pH-7 at 2mV/s) was observed for the
      BiPO4 prepared in the ultrasonication reaction condition of 2h with 60% power.
      Also the obtained specific capacitance was high compared with the conventional
      precipitation method (623F/g at 2mV/s) that revealed the prominence of sonication
      method. Similarly, BiPO4 prepared at pH-7 delivered a maximum specific
      capacitance of 302F/g at 2mA/cm(2) calculated from galvanostatic charge-discharge
      (GCD) method than the other pH conditions. However, the cycling stability of
      BiPO4 (pH-7) was not appreciable even for 200 cycles. So, attempts were taken to
      enhance the cycling stability of the material by employing various carbon
      matrices such as acetylene black, activated carbon and MWCNT instead of carbon
      black during electrode preparation. BiPO4 material with activated carbon
      delivered good capacitance retention compared with other carbon matrices. This
      enhanced electrochemical performance of BiPO4 (pH-7) using activated carbon
      matrix inferred that it could be utilized as efficient negative electrode
      material for pseudocapacitors. 

PMID- 25060120
TI  - Ultra fast and effective treatment of dyes from water with the synergistic effect
      of Ni doped ZnO nanoparticles and ultrasonication.
AB  - The current research work focuses on the synergistic effect of Ni doped ZnO
      nanoparticles and ultrasonication for the degradation of anionic (Fast Green) and
      cationic (Victoria Blue) dyes. Well crystalline monodispersed Ni doped ZnO
      nanoparticles have been synthesized by quick and simple co-precipitation
      technique at low temperature. Synthesized nanoparticles have been characterized
      by X-ray diffraction, UV-vis spectroscopy, transmission electron microscopy and
      energy dispersive X-ray spectroscopy. The effects of operating parameters such as
      catalyst dosage, pH, power dissipation, temperature and dye initial concentration
      have been investigated, and the enhancement in degradation capability of Ni doped
      ZnO with undoped ZnO has also been discussed. The degradation of both the dyes
      follows pseudo-first-order kinetics. In concert with superior activity and reuse
      performance, the current route is promising for the application of ZnO-based
      catalysis for water decontamination. 

PMID- 25060121
TI  - Health disparities among common subcultural identities of young gay men:
      physical, mental, and sexual health.
AB  - Researchers, policymakers, and health agencies have tended to treat gay men as a
      relatively homogeneous population, with little attention given to its many
      subcultural identities. In this study, we focused on young gay men and
      investigated a range of health-related differences according to common
      subcultural identities, such as Bear, Cub, and Twink. In a nationwide cross
      sectional online survey of 1,034 Australian gay men aged 18-39 years, 44%
      reported a subcultural identity, the two most common being Cub (9%) and Twink
      (20%). Logistic and linear regression analyses compared Cub- and Twink-identified
      men and those without a subcultural identity (Non-identified) on a range of
      health-related outcomes. After adjusting for differences in age and body mass
      index (BMI), Twink-identified men had the highest risk profile overall, including
      significantly higher rates of smoking tobacco and alcohol consumption. They were
      also significantly more likely to report engaging in receptive anal sex. In
      addition, Cub-identified men were significantly more likely to report being in an
      ongoing relationship while Non-identified men were significantly less likely to
      report experiences of discrimination in the past 12 months. Differences on
      measures of mental health between the three groups were no longer significant
      after adjusting for age and BMI. In summary, we found numerous health-related
      differences according to subcultural identity that warrant further investigation
      by researchers, health agencies, and others concerned with further understanding
      and addressing health-related challenges of gay men.

PMID- 25060122
TI  - Stress and coping with racism and their role in sexual risk for HIV among African
      American, Asian/Pacific Islander, and Latino men who have sex with men.
AB  - The deleterious effects of racism on a wide range of health outcomes, including
      HIV risk, are well documented among racial/ethnic minority groups in the United
      States. However, little is known about how men of color who have sex with men
      (MSM) cope with stress from racism and whether the coping strategies they employ
      buffer against the impact of racism on sexual risk for HIV transmission. We
      examined associations of stress and coping with racism with unprotected anal
      intercourse (UAI) in a sample of African American (N = 403), Asian/Pacific
      Islander (N = 393), and Latino (N = 400) MSM recruited in Los Angeles County, CA
      during 2008-2009. Almost two-thirds (65 %) of the sample reported being stressed
      as a consequence of racism experienced within the gay community. Overall, 51 % of
      the sample reported having UAI in the prior 6 months. After controlling for
      race/ethnicity, age, nativity, marital status, sexual orientation, education, HIV
      serostatus, and lifetime history of incarceration, the multivariate analysis
      found statistically significant main effects of stress from racism and avoidance
      coping on UAI; no statistically significant main effects of dismissal,
      education/confrontation, and social-support seeking were observed. None of the
      interactions of stress with the four coping measures were statistically
      significant. Although stress from racism within the gay community increased the
      likelihood of engaging in UAI among MSM of color, we found little evidence that
      coping responses to racism buffered stress from racism. Instead, avoidance coping
      appears to suggest an increase in UAI. 

PMID- 25060123
TI  - Negative pressure wound therapy facilitates closure of large congenital abdominal
      wall defects.
AB  - The degree of viscero-abdominal disproportion often makes single-stage reduction
      difficult in large abdominal wall defects, without risking respiratory or
      hemodynamic compromise. As a consequence, clinicians have adopted a number of
      different methods to control these defects. Repair may be in the neonatal period,
      or later in life. Delayed repairs require epithelialization of the gastroschisis
      or omphalocele. Definitive repair may be in single or multiple stages. This paper
      describes four children in whom negative pressure wound therapy (NPWT) was used
      to facilitate closure of these complex defects. 

PMID- 25060124
TI  - Affective temperaments in pregnancy.
AB  - AIM: There are many studies on the mood disorders that occur during pregnancy,
      but no studies that question how affective temperaments, which are the
      antecedents of the mood disorders, are influenced by pregnancy. This study aims
      to examine the affective temperaments in women without any psychiatric diagnoses
      during the pregnancy period. METHOD: The study included 100 pregnant women at the
      third trimester of their pregnancy (pregnant group) and 75 non-pregnant women
      (control group). Structured Clinical Interview for DSM Axis-I Disorders (SCID-I)
      was used for the evaluation of psychiatric disorders; Temperament Evaluation of
      Memphis, Pisa, Paris and San Diego Auto-questionnaire (TEMPS-A) was used for the
      evaluation of affective temperaments. RESULTS: The cyclothymic, irritable and
      anxious temperament scores of the pregnant women were significantly lower than
      that of the non-pregnant women (p < 0.05). Pregnancy predicted lower scores of
      cyclothymic, irritable and anxious temperaments. Younger age and lower levels of
      education were predictors of higher cyclothymic, anxious and depressive
      temperament scores. Younger age also predicted higher irritable temperament
      scores. CONCLUSION: The third trimester of pregnancy is associated with
      significantly lower affective temperament. Future studies may help to understand
      the biological background of the present findings.

PMID- 25060125
TI  - Relief of uterine bleeding by cyclic administration of dienogest for
      endometriosis.
AB  - OBJECTIVE: This study assessed the relief of uterine bleeding and clinical
      symptoms during cyclic administration of dienogest for the treatment of
      endometriosis. METHODS: In total, 25 patients undergoing ovarian cyst enucleation
      and given dienogest participated in this study. Dienogest 2 mg/day was
      administered for 3 weeks, and the drug was then withdrawn for 1 week (cyclic
      administration of dienogest). This 4-week cycle was repeated six times. Patients'
      records were prospectively analyzed for the number of days on which any uterine
      bleeding occurred, as well as menstrual pain before and after the start of
      dienogest administration were evaluated with a view to using the data obtained
      herein as the basis. RESULTS: During the period of cyclic administration of
      dienogest, uterine bleeding occurred on 5.8 to 7.7 days per 4-week period on an
      average through cycles. Of uterine bleeding episodes, menstruation-like uterine
      bleeding was present in about 80% of patients. The visual analog scale (VAS)
      value for menstrual pain significantly decreased from 3.8 before dienogest
      administration after surgery to 1.5 at the completion of cycle 1, VAS remained
      low thereafter. CONCLUSION: These results raise the possibility that cyclic
      administration of dienogest may relieve lessen uterine bleeding, a major adverse
      event and menstrual pain.

PMID- 25060126
TI  - Timing of pre-dose baseline electrocardiograms in clinical trials: increased
      sampling over a prolonged baseline period worsens variance of QTc.
AB  - BACKGROUND AND PURPOSE: The US Food and Drug Administration (US FDA) currently
      recommends recording of electrocardiograms (ECGs) prior to drug administration in
      thorough QT studies over an hour or more time to improve reliability of baseline
      ECG values. However, the baseline period is usually in the morning during a
      period of intense trial activity and rapid circadian change in QTc. The purpose
      of this study was to determine if the practice of recording an extended baseline
      does, in fact, decrease QTc variance at baseline. METHODS: ECG data from three
      thorough QT studies (TQTS) in which three ECGs (commonly referred to as
      triplicates) were recorded at each of three pre-specified time points during the
      60 to 90 minutes before drug administration were analyzed by determining the
      intra-subject and inter-subject standard deviation (SD) of QTcF (Fridericia
      correct QT) for each of the three pre-drug time points and for the three time
      points combined. RESULTS: QTcF was relatively normally distributed in each study.
      Intra-subject variability of QTcF was greater for the combined triplicate
      recordings than for the individual triplicates at baseline treatment time points
      in 39 of 42 cases (93%). This was the case in 48% of the comparisons in the inter
      subject analysis. CONCLUSIONS: The practice of recording three sets of triplicate
      ECGs over an hour or more before drug administration in a TQTS increases
      variability of baseline QTcF consistently in cross-over designed trials, and in
      roughly half of parallel comparisons. Higher variability suggests that the three
      triplicate approach does not provide a more reliable baseline value. Less
      variability of QTcF can be obtained by simply recording one triplicate prior to
      drug administration. This principal may apply to other ECG and other
      physiological variables that have a monotonic circadian trend or that may be
      affected by intense trial activity during the pre-drug hour.

PMID- 25060127
TI  - Regional myocardial dysfunction assessed by two-dimensional speckle tracking
      echocardiography in systemic sclerosis patients with fragmented QRS complexes.
AB  - BACKGROUND: The aim of the study was to explore the relation between regional
      myocardial dysfunction and fragmented QRS (fQRS) complexes in systemic sclerosis
      (SSc). METHODS: Fifty-three SSc patients and 26 controls were included. All
      subjects underwent speckle tracking echocardiography for evaluation of left
      ventricular (LV) function and ECG to check for fQRS complexes. RESULTS: SSc
      patients had significantly lower LV global longitudinal, radial and
      circumferential strain and twist compared to controls. Thirteen SSc patients had
      fQRS (DII, DIII, aVF leads in eleven patients and V1 to V5 leads in two patients)
      and they had significantly lower global longitudinal and circumferencial strain
      compared to SSc patients with normal QRS. The SSc patients with fQRS in DII,
      DIII, and aVF leads had impaired longitudinal strain and delay in time to peak
      longitudinal strain in inferior LV segments compared to those with normal QRS.
      CONCLUSION: fQRS is associated with lower strain measures in SSc patients
      indicating impairment in LV function.

PMID- 25060128
TI  - The pathophysiologic aspects and clinical implications of electrocardiographic
      parameters of ventricular conduction delay in repaired tetralogy of Fallot.
AB  - The 12-lead surface electrocardiogram is a valuable and feasible clinical tool in
      the management of patients following tetralogy of Fallot (TOF) repair. The
      importance of QRS duration in TOF patients has long been acknowledged. A
      prolonged QRS complex has been associated with increased risk for subsequent life
      threatening ventricular arrhythmia and sudden cardiac death. Our current ability
      to risk-stratify TOF patients for malignant arrhythmogenic events primarily on
      the basis of QRS duration is rather limited. Nevertheless, increasing evidence
      suggests that QRS morphology and duration may be useful as surrogate markers of
      infundibular and regional right ventricular myocardial disease. The aim of this
      review is to provide a critical appraisal of the clinical implications of
      established and new electrocardiographic markers of ventricular conduction delay
      in TOF patients following surgical correction with a particular focus on QRS
      duration, lengthening, and fragmentation. In addition, the pathophysiological
      background of these parameters is addressed. 

PMID- 25060129
TI  - Differential diagnosis between left ventricular hypertrophy and cardiomyopathy in
      childhood.
AB  - The sensitivity and specificity of the electrocardiogram for the diagnosis of
      left ventricular hypertrophy of different etiologies are described. The
      sensitivity of the electrocardiogram for detecting left ventricular pressure
      overload is substantially lower (<35%) than the sensitivity for detecting
      evidence of a cardiomyopathy (55% to around 87%). Attention is drawn to the
      finding that in many differing etiologies of left ventricular hypertrophy ST-T
      wave changes commonly referred to as "strain"-pattern are a harbinger of an
      increased risk of malignant cardiac arrhythmias and sudden death. In the most
      common pediatric cause of sudden death, hypertrophic cardiomyopathy, a described
      ECG risk score, which scores both voltage and repolarization abnormalities, is
      the most powerful predictor hitherto described for predicting the risk of sudden
      death in this diagnosis. A point score over 5 points gives a relative risk for
      sudden death of 24.3 with a sensitivity of 96% and a specificity of 78% in
      childhood. 

PMID- 25060130
TI  - An atypical case of vagally mediated atrial fibrillation in an elderly woman:
      electrocardiographic caveats to diagnosis.
AB  - Vagally mediated paroxysmal atrial fibrillation is typically described to occur
      in otherwise healthy young-to-middle aged males during periods of high vagal
      tone. We report a case of cardioinhibitory type neurocardiogenic syncope
      associated with atrial fibrillation in an elderly female during episodes of
      nausea. This was replicated during tilt-table testing. The atrial fibrillation
      was part of a unique snap shot of the entire electrophysiological spectrum of the
      vagal response captured in detail in this index patient. 

PMID- 25060131
TI  - Interleukin-18 and interferon gamma levels in preeclampsia: a systematic review
      and meta-analysis.
AB  - PROBLEM: This systematic review and meta-analysis aimed to investigate the
      relationship between preeclampsia (PE) and circulating interleukin-18 (IL-18) and
      interferon gamma (IFN-gamma). METHOD OF STUDY: Three electronic databases
      (PubMed, EMBASE, and Web of Science) were searched. RESULTS: Eleven studies with
      947 participants reporting IL-18 and 16 studies with 2230 subjects reporting IFN
      gamma were included. There was no significant difference in the IL-18 levels in
      PE patients compared with controls. However, IFN-gamma was found to be
      significantly higher in women with PE than that in normotensive pregnant women
      (standardized mean difference = 0.93; 95% confident interval: 0.07, 1.79).
      Furthermore, stratification by specimen type, quality score, method of estimation
      of mean and standard deviation, and whether sampling not in labor/premature
      rupture of membrane/infection also showed significant differences in standardized
      mean difference of IL-18, as well as IFN-gamma. CONCLUSION: This meta-analysis
      suggests that circulating higher IFN-gamma levels may be associated with
      preeclampsia.

PMID- 25060132
TI  - An Expert Map of Gambling Risk Perception.
AB  - The purpose of the current study was to investigate the moderating or mediating
      role played by risk perception in decision-making, gambling behaviour, and
      disordered gambling aetiology. Eleven gambling expert clinicians and researchers
      completed a semi-structured interview derived from mental models and grounded
      theory methodologies. Expert interview data was used to construct a comprehensive
      expert mental model 'map' detailing risk-perception related factors contributing
      to harmful or safe gambling. Systematic overlapping processes of data gathering
      and analysis were used to iteratively extend, saturate, test for exception, and
      verify concepts and emergent themes. Findings indicated that experts considered
      idiosyncratic beliefs among gamblers result in overall underestimates of risk and
      loss, insufficient prioritization of needs, and planning and implementation of
      risk management strategies. Additional contextual factors influencing use of risk
      information (reinforcement and learning; mental states, environmental cues,
      ambivalence; and socio-cultural and biological variables) acted to shape risk
      perceptions and increase vulnerabilities to harm or disordered gambling. It was
      concluded that understanding the nature, extent and processes by which risk
      perception predisposes an individual to maintain gambling despite adverse
      consequences can guide the content of preventative educational responsible
      gambling campaigns. 

PMID- 25060133
TI  - Effects of VIE tagging and partial tissue sampling on the immune response of
      three-spined stickleback Gasterosteus aculeatus.
AB  - A 14 day experiment on effects of visible implant elastomer (VIE) tagging and
      spine-clipping of three-spined stickleback Gasterosteus aculeatus showed
      significant increases in immune response, particularly in the
      granulocyte:lymphocyte ratio, in both treatments and the sham control. A minimum
      two-week recovery after handling, anaesthesia, tagging and spine-clipping is
      recommended to minimize effect of manipulation on the immune system. 

PMID- 25060134
TI  - Fumaric acid production by Torulopsis glabrata: engineering the urea cycle and
      the purine nucleotide cycle.
AB  - A multi-vitamin auxotrophic Torulopsis glabrata strain, a pyruvate producer, was
      further engineered to produce fumaric acid. Using the genome-scale metabolic
      model iNX804 of T. glabrata, four fumaric acid biosynthetic pathways, involving
      the four cytosolic enzymes, argininosuccinate lyase (ASL), adenylosuccinate lyase
      (ADSL), fumarylacetoacetase (FAA), and fumarase (FUM1), were found. Athough
      single overexpression of each of the four enzymes in the cytosol improved fumaric
      acid production, the highest fumaric acid titer (5.62 g L(-1) ) was obtained with
      strain T.G-ASL(H) -ADSL(L) by controlling the strength of ASL at a high level and
      ADSL at a low level. In order to further improve the production of fumaric acid,
      the SpMAE1 gene encoding the C4 -dicarboxylic acids transporter was overexpressed
      in strain T.G-ASL(H) -ADSL(L) -SpMAE1 and the final fumaric acid titer increased
      to 8.83 g L(-1) . This study provides a novel strategy for fumaric acid
      biosynthesis by utilizing the urea cycle and the purine nucleotide cycle to
      enhance the bridge between carbon metabolism and nitrogen metabolism.

PMID- 25060135
TI  - Synthesis of silica vesicles with controlled entrance size for high loading,
      sustained release, and cellular delivery of therapeutical proteins.
AB  - A rationally designed two-step synthesis of silica vesicles is developed with the
      formation of vesicular structure in the first step and fine control over the
      entrance size by tuning the temperature in the second step. The silica vesicles
      have a uniform size of ~50 nm with excellent cellular uptake performance. When
      the entrance size is equal to the wall thickness, silica vesicles after
      hydrophobic modification show the highest loading amount (563 mg/g) towards
      Ribonuclease A with a sustained release behavior. Consequently, the silica
      vesicles are excellent nano-carriers for cellular delivery applications of
      therapeutical biomolecules. 

PMID- 25060136
TI  - Dual cell protective mechanisms activated by differing levels of oxidative stress
      in HT22 murine hippocampal cells.
AB  - Oxidative stress is recognized as one of the pathogenic mechanisms involved in
      neurodegenerative disease. However, recent evidence has suggested that regulation
      of cellular fate in response to oxidative stress appears to be dependent on the
      stress levels. In this study, using HT22 cells, we attempted to understand how an
      alteration in the oxidative stress levels would influence neuronal cell fate.
      HT22 cell viability was reduced with exposure to high levels of oxidative stress,
      whereas, low levels of oxidative stress promoted cell survival. Erk1/2 activation
      induced by a low level of oxidative stress played a role in this cell protective
      effect. Intriguingly, subtoxic level of H2O2 induced expression of a growth
      factor, progranulin (PGRN), and exogenous PGRN pretreatment attenuated HT22 cell
      death induced by high concentrations of H2O2 in Erk1/2-dependent manner.
      Together, our study indicates that two different cell protection mechanisms are
      activated by differing levels of oxidative stress in HT22 cells. 

PMID- 25060137
TI  - Complete bronchial obstruction by granuloma in a paediatric patient with
      translaryngeal endotracheal tube: a case report.
AB  - INTRODUCTION: Although continuous or frequent stimuli in tracheostomized patients
      may cause tracheal granulomas, little is known about management of patients with
      translaryngeal intubation. CASE PRESENTATION: A 1-month-old Japanese boy,
      weighing 3.5kg, was admitted to our hospital owing to cardiac failure caused by
      an atrial septal defect and intractable arrhythmia. To treat his unstable
      cardiovascular status, surgery was performed to close his atrial septal defect.
      After the operation, stenosis was detected by auscultation and flow limitation
      worsened. A bronchoscopy revealed granulomas completely obstructing his right
      bronchus and partially obstructing his left bronchus. Dexamethasone infusion
      partially reduced the mass, after which removal by yttrium aluminium garnet laser
      was tried. The airway obstruction was not resolved, however, because of granuloma
      reproliferation. Budesonide (aerosol liquid) inhalation was started, and tissue
      was reduced using an yttrium aluminium garnet laser and physically removed using
      forceps. After continued budesonide inhalation, he was successfully liberated
      from the ventilator. CONCLUSIONS: Life-threatening airway obstruction by
      granulomas developed in a translaryngeally intubated paediatric patient. The
      granuloma was detected after a couple of weeks of intubation. A bronchial
      granuloma is rare in paediatric patients. It should be suspected with evidence of
      bronchial obstruction. Treatment with corticosteroids and surgery using a laser
      maybe indicated.

PMID- 25060138
TI  - Academy deliverables: GENIE.

PMID- 25060139
TI  - Position of the Academy of Nutrition and Dietetics: nutrition guidance for
      healthy children ages 2 to 11 years.
AB  - It is the position of the Academy of Nutrition and Dietetics that children ages 2
      to 11 years should achieve optimal physical and cognitive development, maintain
      healthy weights, enjoy food, and reduce the risk of chronic disease through
      appropriate eating habits and participation in regular physical activity. Rapid
      increases in the prevalence of childhood obesity during the 1980s and 1990s
      focused attention on young children's overconsumption of energy-dense, nutrient
      poor foods and beverages and lack of physical activity. While recent data suggest
      a stabilization of obesity rates, several public health concerns remain. These
      include the most effective ways to promote healthy weights, the number of
      children living in food insecurity, the under-consumption of key nutrients, and
      the early development of diet-related risks for chronic diseases, such as
      cardiovascular disease, type 2 diabetes, cancer, obesity, and osteoporosis. This
      Position Paper reviews what children 2 to 11 years old in the United States are
      reportedly eating, explores trends in food and nutrient intakes, and examines the
      impact of federal nutrition programs on child nutrition. Current dietary
      recommendations and guidelines for physical activity are also discussed. The
      roles of parents and caregivers in influencing the development of life-long
      healthy eating behaviors are highlighted. The Academy of Nutrition and Dietetics
      works with other allied health and food industry professionals to translate
      dietary recommendations and guidelines into positive, practical health messages.
      Specific recommendations and sources of science-based nutrition messages to
      improve the nutritional well-being of children are provided for food and
      nutrition practitioners. 

PMID- 25060140
TI  - Using Academy Standards of Excellence in Nutrition and Dietetics for organization
      self-assessment and quality improvement.
AB  - Standards of Excellence in Nutrition and Dietetics for an Organization is a self
      assessment tool to measure and evaluate an organization's program, services, and
      initiatives that identify and distinguish the Registered Dietitian Nutritionist
      (RDN) brand as the professional expert in food and nutrition. The Standards of
      Excellence will serve as a road map to recognize RDNs as leaders and
      collaborators. Standards of Excellence criteria apply to all practice segments of
      nutrition and dietetics: health care, education and research, business and
      industry, and community nutrition and public health. Given the membership's call
      to action to be recognized for their professional expertise, the Academy of
      Nutrition and Dietetics Quality Management Committee developed four Standards of
      Excellence in Nutrition and Dietetics for Organizations: Quality of Leadership,
      Quality of Organization, Quality of Practice, and Quality of Outcomes. Within
      each standard, specific indicators provide strategies for an organization to
      demonstrate excellence. The Academy will develop a self-evaluation scoring tool
      to assist the organization in applying and implementing one or more of the
      strategies in the Standards of Excellence indicators. The organization can use
      the self-assessment tool to establish itself as a Center of Excellence in
      Nutrition and Dietetics. The role examples illustrate initiatives RDNs and
      organizations can take to identify themselves as a Center of Excellence in
      Nutrition and Dietetics. Achieving the Excellence level is an important
      collaborative initiative between nutrition and dietetics organizations and the
      Academy to provide increased autonomy, supportive management, respect within
      peers and community, opportunities for professional development, support for
      further education, and compensation for the RDN. For purposes of the Standards,
      "organization" means workplace or practice setting. 

PMID- 25060141
TI  - I have a client who wants to follow the Mediterranean diet--where do I start?

PMID- 25060142
TI  - Reversing death: the miracle of modern medicine.
AB  - Breakthroughs in emergency medicine have enabled science to halt and even reverse
      death. However, these advances have inadvertently led science into a domain that
      has traditionally been the purview of theology and philosophy. Steve Paulson,
      executive producer and host of To the Best of Our Knowledge, moderated a
      discussion that included emergency medicine experts Lance B. Becker and Sam
      Parnia, and neurosurgeon Stephan A. Mayer; they discussed recent discoveries and
      emerging technologies in resuscitation science and the ethical dilemmas they
      sometimes confront during medical crises. The following is an edited transcript
      of the discussion from October 9, 2013, 7:00-8:30 PM, at the New York Academy of
      Sciences in New York City. 

PMID- 25060143
TI  - Majorana modes and p-wave superfluids for fermionic atoms in optical lattices.
AB  - The quest for realization of non-Abelian phases of matter, driven by their
      possible use in fault-tolerant topological quantum computing, has been
      spearheaded by recent developments in p-wave superconductors. The chiral
      p(x)+ip(y)-wave superconductor in two-dimensions exhibiting Majorana modes
      provides the simplest phase supporting non-Abelian quasiparticles and can be seen
      as the blueprint of fractional topological order. Alternatively, Kitaev's
      Majorana wire has emerged as an ideal toy model to understand Majorana modes.
      Here we present a way to make the transition from Kitaev's Majorana wires to two
      dimensional p-wave superconductors in a system with cold atomic gases in an
      optical lattice. The main idea is based on an approach to generate p-wave
      interactions by coupling orbital degrees of freedom with strong s-wave
      interactions. We demonstrate how this design can induce Majorana modes at edge
      dislocations in the optical lattice, and we provide an experimentally feasible
      protocol for the observation of the non-Abelian statistics.

PMID- 25060144
TI  - The SIMS Screen for feigned mental disorders: the development of detection-based
      scales.
AB  - Time-efficient screens for feigned mental disorders (FMDs) constitute important
      tools in forensic assessments. The Structured Inventory of Malingered
      Symptomatology (SIMS) is a 75-item true-false questionnaire that has been
      extensively studied as an FMD screen. However, the SIMS scales are not based on
      established detection strategies, and only its total score is utilized as a
      feigning screen. This investigation develops two new feigning scales based on
      well-established detection-strategies: rare symptoms (RS) and symptom
      combinations (SC). They are studied in a between-subjects simulation design using
      inpatients with partial-malingering (i.e., patients with genuine disorders asked
      to feign greater disabilities) conditions. Subject to future cross-validation,
      the SC scale evidenced the highest effect size (d=2.01) and appeared the most
      effective at ruling out examinees, who have a high likelihood of genuine
      responding.

PMID- 25060145
TI  - Plasma natriuretic peptides and incidence of subtypes of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Natriuretic peptides predict poor outcomes in
      cardiovascular disease. However, the knowledge of their relationship to stroke is
      limited and prospective studies from the general population are few. The purpose
      of this study was to explore the relationship between N-terminal pro-brain
      natriuretic peptide (NT-proBNP) and midregional pro-atrial natriuretic peptide
      (MR-proANP) plasma levels and the risk for ischemic stroke and its subtypes.
      METHODS: NT-proBNP and MR-proANP were measured in fasting blood samples from
      4,862 subjects (40.2% men, mean age 57.5 +/- 6.0 years) without cardiovascular
      disease from the Malmo Diet and Cancer Study, a prospective, population-based
      study in Sweden. Incidence of ischemic stroke was monitored over a mean follow-up
      of 14.9 +/- 3.0 years. Stroke cases were etiologically classified according to
      the TOAST classification. Cox proportional-hazards regression was used to study
      the incidence of stroke in relationship to NT-proBNP and MR-proANP. RESULTS:
      During follow-up, 227 had a first-ever ischemic stroke (large-artery
      atherosclerosis, n = 35; cardioembolic stroke, n = 44; small-artery occlusion, n
      = 80; undetermined cause, n = 68). In the age- and sex-adjusted model, only NT
      proBNP was associated with total ischemic stroke. This association was completely
      explained by an increased incidence of cardioembolic stroke. Adjusted for
      cardiovascular risk factors (age, sex, hypertension, diabetes, smoking, body mass
      index and low-density lipoprotein cholesterol), the hazard ratios (HRs, 95%
      confidence interval, 95% CI) for cardioembolic stroke were 1.00 (reference), 1.42
      (0.34-6.00), 2.79 (0.77-10.12) and 5.64 (1.66-19.20), respectively, for the 1st,
      2nd, 3rd and 4th quartiles of NT-proBNP. The corresponding HRs (95% CIs) for
      quartiles of MR-proANP were 1.00 (reference), 1.83 (0.55-6.14), 1.20 (0.33-4.34)
      and 3.96 (1.31-11.99), respectively. In total, 335 (6.9%) subjects were diagnosed
      with atrial fibrillation during follow-up. Among the cardioembolic stroke cases,
      30% were diagnosed with atrial fibrillation before the stroke event and another
      36% within 6 months after the stroke. Of the cardioembolic stroke cases with
      atrial fibrillation, 59% were in the top quartile of NT-proBNP, 69% in the top
      quartile of MR-proANP and 79% were either in the top quartile of NT-proBNP or in
      the top quartile of MR-proANP. CONCLUSION: High plasma levels of NT-proBNP and MR
      proANP are associated with a substantially increased risk of cardioembolic
      stroke, but not with other subtypes of ischemic stroke. The results suggest that
      assessment of stroke risk, including electrocardiography, is warranted in
      subjects with high NT-proBNP or MR-proANP.

PMID- 25060146
TI  - Perturbation of spin crossover behavior by covalent post-synthetic modification
      of a porous metal-organic framework.
AB  - Covalent post-synthetic modification is a versatile method for gaining high-level
      synthetic control over functionality within porous metal-organic frameworks and
      for generating new materials not accessible through one-step framework syntheses.
      Here we apply this topotactic synthetic approach to a porous spin crossover
      framework and show through detailed comparison of the structures and properties
      of the as-synthesised and covalently modified phases that the modification
      reaction proceeds quantitatively by a thermally activated single-crystal-to
      single-crystal transformation to yield a material with lowered spin-switching
      temperature, decreased lattice cooperativity, and altered color. Structure
      function relationships to emerge from this comparison show that the approach
      provides a new route for tuning spin crossover through control over both outer
      sphere and steric interactions. 

PMID- 25060147
TI  - Structural insights into selective agonist actions of tamoxifen on human estrogen
      receptor alpha.
AB  - Tamoxifen-an anti-estrogenic ligand in breast tissues used as a first-line
      treatment in estrogen receptor (ER)-positive breast cancers-is associated with
      the development of resistance followed by resumption of tumor growth in about 30
      % of cases. Whether tamoxifen assists in proliferation in such cases or whether
      any ligand-independent pathway to transcription exists is not fully understood;
      also, no ERalpha mutants have been detected so far that could lead to tamoxifen
      resistance. Using in silico conformational analysis of the ERalpha ligand binding
      domain (LBD), in the absence and presence of selective agonist
      (diethylstilbestrol; DES), antagonist (Faslodex; ICI), and selective estrogen
      receptor modulator (SERM; 4-hydroxy tamoxifen; 4-OHT) ligands, we have elucidated
      ligand-responsive structural modulations of the ERalpha-LBD dimer in its agonist
      and antagonist complexes to address the issue of "tamoxifen resistance". DES and
      ICI were found to stabilize the dimer in their agonist and antagonist
      conformations, respectively. The ERalpha-LBD dimer without the presence of any
      bound ligand also led to a stable structure in agonist conformation. However,
      binding of 4-OHT to the antagonist structure led to a flexible conformation
      allowing the protein to visit conformations populated by agonists as was evident
      from principal component analysis and radius of gyration plots. Further, the
      relaxed conformations of the 4-OHT bound protein exhibited a diminished size of
      the co-repressor binding pocket in the LBD, thus signaling a partial blockage of
      the co-repressor binding motif. Thus, the ability of 4-OHT-bound ERalpha-LBD to
      assume flexible conformations visited by agonists and reduced co-repressor
      binding surface at the LBD provide crucial structural insights into tamoxifen
      resistance that complement our existing understanding. 

PMID- 25060148
TI  - Topological analyses of time-dependent electronic structures: application to
      electron-transfers in methionine enkephalin.
AB  - We have studied electron transfers (ET) between electron donors and acceptors,
      taking as illustrative example the case of ET in methionine enkephalin. Recent
      pulse and gamma radiolysis experiments suggested that an ultrafast ET takes place
      from the C-terminal tyrosine residue to the N-terminal, oxidized, methionine
      residue. According to standard theoretical frameworks like the Marcus theory, ET
      can be decomposed into two successive steps: i) the achievement through thermal
      fluctuations, of a set of nuclear coordinates associated with degeneracy of the
      two electronic states, ii) the electron tunneling from the donor molecular
      orbital to the acceptor molecular orbital. Here, we focus on the analysis of the
      time-dependent electronic dynamics during the tunneling event. This is done by
      extending the approaches based on the topological analyses of stationary
      electronic density and of the electron localization function (ELF) to the time
      dependent domain. Furthermore, we analyzed isosurfaces of the divergence of the
      current density, showing the paths that are followed by the tunneling electron
      from the donor to the acceptor. We show how these functions can be calculated
      with constrained density functional theory. Beyond this work, the topological
      tools used here can open up new opportunities for the electronic description in
      the time-dependent domain. 

PMID- 25060149
TI  - Comparison of several protocols for the computational prediction of the maximum
      absorption wavelength of chrysanthemin.
AB  - UV-Vis spectra were calculated using time-dependent density functional theory for
      the chrysanthemin pigment, which is used as natural dye in dye sensitized solar
      cells. To this end, we studied four different calculation protocols in order to
      obtain the best approximation according to the maximum absorption wavelength
      (lambdamax) of the experimental spectrum. Furthermore, the optimized geometry,
      highest occupied molecular orbitals, lowest unoccupied molecular orbitals and
      electron density were calculated and analyzed. Several chemical models were used
      with and without the presence of the chlorine atom: the chosen functionals,
      B3LYP, PBE0 and the M06 family, represent various approximations with different
      fractions of Hartree-Fock exchange energy. These functionals were combined with
      the 6-31+G (d), 6-311+G (d) and the MIDIX+basis sets. All of these calculation
      protocols proved a good option, though the B3LYP/MIDIX+chemistry model was the
      best for predicting the lambdamax value, using the equilibrium calculation
      protocol (M1a) in the presence of chlorine.

PMID- 25060150
TI  - Two novel glucagon receptor antagonists prove effective therapeutic agents in
      high-fat-fed and obese diabetic mice.
AB  - AIMS: To examine the effect of two novel, enzymatically stable, glucagon receptor
      peptide antagonists, on metabolic control in two mouse models of
      obesity/diabetes. METHOD: The effects of twice daily i.p. administration of
      desHis(1)Pro(4)Glu(9)-glucagon or desHis(1)Pro(4)Glu(9)Lys(12)FA-glucagon for 10
      days on metabolic control in high-fat-fed (HFF; 45% fat) and obese diabetic
      (ob/ob) mice were compared with saline-treated controls. RESULTS: Neither
      analogue altered body weight or food intake in either model over 10 days;
      however, treatment with each peptide restored non-fasting blood glucose towards
      normal control values in HFF mice. Basal glucose was also reduced (p < 0.01) in
      desHis(1)Pro(4)Glu(9)Lys(12)FA-glucagon treated ob/ob mice by day 10, coinciding
      with increases (p < 0.001) in circulating insulin. At the end of the treatment
      period, both analogues significantly (p < 0.05-0.01) improved oral and i.p.
      glucose tolerance (p < 0.05) and peripheral insulin sensitivity, increased
      pancreatic insulin and glucagon content (p < 0.05-0.01) and decreased (p < 0.05)
      cholesterol levels in HFF mice. Similarly beneficial metabolic effects on oral
      glucose tolerance (p < 0.01) and pancreatic insulin content (p < 0.05) were
      observed in ob/ob mice, especially after desHis(1)Pro(4)Glu(9)Lys(12)FA-glucagon
      treatment. No significant differences in circulating triglycerides or aspects of
      indirect calorimetry were noted between peptide treatment groups and respective
      control HFF and ob/ob mice. Finally, glucagon-mediated elevations of glucose and
      insulin were significantly (p < 0.05-0.01) annulled after 10 days of
      desHis(1)Pro(4)Glu(9)-glucagon or desHis(1)Pro(4)Glu(9)Lys(12)FA-glucagon
      treatment in both animal models. CONCLUSION: These data indicate that peptide
      based glucagon receptor antagonists can reverse aspects of genetically and
      dietary-induced obesity-related diabetes.

PMID- 25060151
TI  - Psycho-oncologic interventions to reduce distress in cancer patients: a meta
      analysis of controlled clinical studies published in People's Republic of China.
AB  - OBJECTIVE: This study aimed to summarize the current result of controlled
      clinical studies published in China and analyzed the effect of psycho-oncologic
      interventions on distress of cancer patients. METHODS: Electronic searches were
      conducted in four databases. The study inclusion criteria were established on the
      basis of the PICOS (population, intervention, comparator, outcomes, and study
      design) framework. The main outcome measures were emotional distress, anxiety,
      and depression. Meta-analytic techniques were applied to analyze published data
      from the retrieved studies. RESULTS: A total of 207 controlled studies (involving
      19,607 cancer patients) were included, among which 31 studies (3007 patients)
      were meta-analyzed. Pooled analysis showed large effects for psycho-oncologic
      interventions on anxiety (d = -8.71, p < 0.001) and depression (d = -8.12, p <
      0.001). Health education combined with psychological support (d = -8.17, p =
      0.04) or with relaxation training (d = -12.95, p < 0.001) significantly lowered
      the anxiety level in cancer patients. However, health education combined with
      relaxation training did not lower the depression levels (p > 0.05). Nurses were
      the primary health professionals (69.08%) responsible for delivering
      interventions. Meanwhile, none of the reports followed all the items of the
      consolidated standards of reporting trials checklist. Most studies suffered from
      some flaws concerning blinding, randomization procedures, participant follow-up,
      attrition, and so on. CONCLUSION: The findings pointed out that psycho-oncologic
      interventions significantly reduced distress in cancer patients of China;
      however, the quality of the randomized controlled trials was low. In the future,
      reports on controlled clinical studies should follow the consolidated standards
      of reporting trials statement and supply more comprehensive information.

PMID- 25060152
TI  - Regulatory T cells in the actinic cheilitis.
AB  - BACKGROUND: Actinic cheilitis (AC) is an oral potentially malignant lesion which
      is the counterpart of actinic keratosis of the skin and has potential to develop
      into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in
      modulating the antitumor immune responses. The presence of regulatory T cells in
      potentially malignant lesions has not been described. We chose investigate the
      involvement of regulatory T cells in potentially malignant lesions. METHODS: The
      frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and
      lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified
      by ELISA. Data were compared with samples from healthy subjects. RESULTS: The
      frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in
      AC patients and control subjects. However, the frequencies of IL-10-positive
      Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN
      gamma) and increased interleukin (IL)-10 productions in co-cultures. Furthermore,
      CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells
      suppressed lymphocyte proliferation and pro-inflammatory cytokine production.
      Moreover, high levels of IL-10 and transforming growth factor-beta (TGF-beta),
      and low IFN-gamma were detected in the potentially malignant lesions. CONCLUSION:
      Therefore, our data show that Tregs accumulate in AC lesions, and these cells
      could be suppressing immune responses in a potentially malignant
      microenvironment.

PMID- 25060153
TI  - [Personalized medicine - the wheel has been reinvented].

PMID- 25060154
TI  - Changes and interactions of flourishing, mindfulness, sense of coherence, and
      quality of life in patients of a mind-body medicine outpatient clinic.
AB  - BACKGROUND: Stress-related, behavioral or chronic diseases require a holistic
      therapeutic approach. Mind-body medicine (MBM) uses the interaction between mind,
      body, behavior, and the environment to affect physical and psychological health
      and function. This integrative strategy can be applied in clinical settings,
      e.g., in an outpatient clinic, to improve well-being as well as clinical
      outcomes. We hypothesized an improvement of flourishing, mindfulness, sense of
      coherence, and quality of life through a comprehensive MBM program. In addition,
      we hypothesized correlations between the measures themselves as well as between
      the measures influenced by the intervention. METHODS: We conducted a longitudinal
      cohort study in an outpatient clinic setting (n = 48 patients, with various
      diagnoses). A questionnaire battery, consisting of SF-12, Flourishing Scale (FS,
      FS-D), Freiburg Mindfulness Inventory (FMI), and Sense of Coherence Scale (SOC9),
      was used and applied in a pre-to-post format over a period of 18 weeks. The
      intervention was a 12-week MBM group program, with 1 session of 7 h per week.
      RESULTS: The pre-post comparison of the measures showed significant improvements
      in psychological health, flourishing, mindfulness, and coherence. We were able to
      verify correlations between the measures themselves, apart from physical health.
      Coherence correlated with psychological health, influenced by the intervention.
      Further analyses showed associations between coherence, mindfulness, and
      flourishing. CONCLUSIONS: The MBM program improved measures of psychological
      health and decreased the level of suffering from chronic disease. MBM led to an
      improvement of disease coping and appraisal of individual ailments, thereby
      enhancing quality of life. Personal flourishing, coherence, and mindfulness seem
      to interact with each other.

PMID- 25060155
TI  - Using hospital data and routines to estimate costs and effects of integrative
      care programmes for chronic pain and stress disorders--a feasibility study.
AB  - BACKGROUND: Evidence of cost and effects for comprehensive hospital-based
      integrative care (IC) is scarce. The aim of this study was to explore the
      feasibility of using local hospital data and routines to estimate costs and
      effects of anthroposophic IC programmes for chronic pain and stress disorders in
      Sweden. METHODS: Retrospective analysis of one IC hospital's local administrative
      registry data. Main outcomes embraced patient demographics, programme duration
      and costs, patients' health status (EQ-5D index, 0-1) and self-rated health (EQ
      5D VAS, 0-100), from hospital admittance to discharge. The use of postal
      questionnares for collecting follow-up data after hospital discharge was
      assessed. RESULTS: The IC pain programme had 461 records, all with complete data
      on costs and duration: average programme cost, EUR 5,925 (95% CI 5,780-6,070),
      and duration, 17.8 (SD 4.7) days. The IC stress programme had 263 records, all
      with complete cost and duration data: programme cost, EUR 5,494 (95%CI 5,318
      5,671); duration 18.0 (SD 4.7) days. From admittance to discharge, health status
      improved by 0.23 (95% CI 0.19-0.27) in the pain, and by 0.16 (95% CI 0.12-0.20)
      in the stress programme. Improvements in self-rated health were 20 (95% CI 18
      22), and 21 (95% CI 18-23), respectively. There was a general decrease in
      questionnaire response rate after hospital discharge, whereby 27-32% of
      respondents had completed data after 9 months. CONCLUSIONS: It was feasible to
      use hospital registry data to estimate costs and show positive effects of
      anthroposophic IC programmes for pain and stress disorders in Sweden. Clinical
      implications and the need for long-term follow-up are discussed.

PMID- 25060156
TI  - Effect of orally administered potentized capsaicin and dihydrocapsaicin in
      humans: a homeopathic pathogenetic trial.
AB  - BACKGROUND: A homeopathic pathogenetic trial is a procedure to examine the
      disease-producing effect of any substance on humans. Capsaicin and
      dihydrocapsaicin are known as pain-producing agents. According to the homeopathic
      law of similars, any substance having the capacity to produce certain symptoms
      should also be able to treat them in return, when administered in small
      (potentized) dose. METHODS: In a doubleblind, randomized placebo-controlled
      homeopathic pathogenetic trial with 22 volunteers, 15 received a combination of
      capsaicin and dihydrocapsaicin as a single remedy in 30c potency, while 7
      received placebo. The volunteers' symptoms during 5 weeks were carefully noted as
      per protocol. The participants signed an informed consent, the study was approved
      by the ethics committee, and laboratory investigations were documented and safety
      measures adopted. RESULTS: A preparation of orally administered ultra-high
      diluted capsaicin and dihydrocapsaicin unveiled qualitatively and quantitatively
      distinct symptoms, comparable with effects of the crude substance. Compared to
      placebo, the homeopathic preparation produced significant symptoms in healthy
      human volunteers. These findings can subsequently be used therapeutically.
      CONCLUSION: The administration of potentized capsaicin and dihydrocapsaicin
      combination produced symptoms of pain (and others) in healthy volunteers. This
      preparation can be applied therapeutically following a basic homeopathic
      principle. Further research to confirm the assumptions is warranted.

PMID- 25060157
TI  - Lipid profile and non-cholesterol sterols in obese women's serum after
      supplementing with plant stanol ester.
AB  - BACKGROUND: The aim of this study was to assess the influence of increased plant
      stanol ester intake on lipid profile and serum ratio of non-cholesterol sterols
      to cholesterol in obese women (50 years of age) with dyslipidemia. METHODS: 90
      females were assigned into 2 treatment groups: For a period of 4 weeks, group 1
      was receiving a yoghurt, enriched with 2 g of plant stanol ester (PS group), and
      group 2 was receiving a yoghurt drink without extra stanols. Anthropometric
      measurements included body height and weight. Lipid profile was determined by
      commercially available enzymatic methods. Serum non-cholesterol sterols and
      stanols concentrations were quantitated by gas chromatography. The study was
      single-blind and placebo-controlled. RESULTS: The yoghurt drink enriched with
      plant stanol ester significantly reduced serum total cholesterol, LDL
      cholesterol, and non-HDL cholesterol levels (p < 0.05). No changes were observed
      in HDL cholesterol and triacylglycerol levels. The highest drop of LDL
      cholesterol was noted in the upper quartile of total cholesterol concentrations.
      In the PS group the statistically significant (p < 0.0001) changes were also
      observed in serum ratios of non-cholesterol sterols to cholesterol: campesterol,
      sitosterol, sitostanol, and avenasterol. CONCLUSION: Plant stanol esters
      influence the concentration of total cholesterol, particularly LDL cholesterol.
      This effect seems to be related to the reduced dietary cholesterol absorption.

PMID- 25060158
TI  - Effects of chronic Bryophyllum pinnatum administration on Wistar rat pregnancy.
AB  - BACKGROUND: Drugs used in preterm labor (PTL) have side effects. Research into
      new tocolytic agents is recommended. The plant Bryophyllum pinnatum (Lam.) Oken
      (Kalanchoe pinnata (Lam.) Pers) is used in Anthroposophic Medicine for PTL,
      insomnia, and emotional disturbances. The aim of this study was to evaluate the
      effects of B. pinnatum mother tincture (MT) on Wistar rats and their fetuses
      throughout pregnancy. METHOD: Sixty animals were divided into 6 equal groups:
      controls C1 and C2 received 1 and 25 * the maximum daily dose of a 30% ethanol /
      water solution, serving as vehicle of B. pinnatum MT; B1 and B2 received 1 and 25
      * the maximum daily dose of B. pinnatum MT; and B3 and B4 received 50 and 100 *
      B. pinnatum concentrate. The following parameters were assessed: weight gain;
      maternal and fetal mortality; implantations and resorptions; number and weight of
      fetuses and placentas; major external fetal malformations. RESULTS: Rat weight
      gain (excluding fetal and placental weight) was higher in group B4 and lower in
      group B2. There were no maternal or fetal deaths and no group differences in
      implantations and resorptions or number and weight of fetuses and placentas. No
      macroscopic fetal abnormalities were observed at the 4 dosage levels
      investigated. CONCLUSION: Daily administration of B. pinnatum MT at high doses to
      pregnant Wistar rats interfered with maternal weight gain and did not interfere
      with fetal compartment.

PMID- 25060159
TI  - Introducing a computer-assisted, digital tongue-imaging device for
      standardization of traditional tongue diagnosis.
AB  - BACKGROUND: In Traditional Chinese Medicine (TCM) tongue diagnosis and pulse
      diagnosis are the major diagnostic methods up till now. As western research has
      tended to focus on acupuncture, attempts to standardize the classic diagnostic
      methods have been few. METHODS: A digital camera with a ring flash was fixed in a
      frame, so that the tongue-lens-distance and illumination were kept constant. A
      pilot study testing the inter-methods reliability, test-retest reliability, and
      interrater reliability of 2 observers was conducted: the tongues (1 *) as well as
      the tongue images (2 *) from 76 patients from our ward were assessed with a
      standardized rating list in a randomized order by both observers, who were
      mutually blinded. As primary outcome measure we used agreement beyond chance
      (Cohen's kappa). RESULTS: The colors of the tongue body / the tongue coating were
      the main criteria for the authentic reproduction of the tongue in our images.
      Inter-methods reliability for the color of the tongue body/coating was kappa 0.35
      / 0.34 (p < 0.001) for observer 1 and 0.59 / 0.57 (p < 0.001) for observer 2.
      Test-retest reliability for the color of the tongue body / the tongue coating was
      kappa 0.53 / 0.48 (p< 0.001) for observer 1 and 0.65 / 0.62 (p < 0.001) for
      observer 2. Interrater reliability was generally low. CONCLUSIONS: The introduced
      device represents a first step towards standardization of tongue diagnosis.
      However, inter-methods as well as test-retest reliability vary between observers
      and different morphological characteristics.

PMID- 25060161
TI  - Calculation of volatile anaesthetics consumption from agent concentration and
      fresh gas flow.
AB  - BACKGROUND: The assessment of volatile agents' consumption can be performed by
      weighing vapourisers before and after use. This method is technically demanding
      and unavailable for retrospective analysis of anaesthesia records. Therefore, a
      method based on calculations from fresh gas flow and agent concentration is
      presented here. METHODS: The presented calculation method herein enables a
      precise estimation of volatile agent consumption when average fresh gas flows and
      volatile agent concentrations are known. A pre-condition for these calculations
      is the knowledge of the vapour amount deriving from 1 ml fluid volatile agent.
      The necessary formulas for these calculations and an example for a sevoflurane
      anaesthesia are presented. RESULTS: The amount of volatile agent vapour deriving
      from 1 ml of fluid agent are for halothane 229 ml, isoflurane 195 ml, sevoflurane
      184 m, and desflurane 210 ml. The constant for sevoflurane is used in a
      fictitious clinical case to exemplify the calculation of its consumption in daily
      routine resulting in a total expenditure of 23.6 ml liquid agent. CONCLUSIONS: By
      application of the presented specific volatile agent constants and equations, it
      becomes easy to calculate volatile agent consumption if the fresh gas flows and
      the resulting inhaled concentration of the volatile agent are known. By this
      method, it is possible to extract data about volatile agent consumption both
      ways: (1) retrospectively from sufficiently detailed and accurate anaesthesia
      recordings, as well as (2) by application of this method in a prospective
      setting. Therefore, this method is a valuable contribution to perform
      pharmacoeconomical surveys.

PMID- 25060160
TI  - A systematic review of how studies describe educational interventions for
      evidence-based practice: stage 1 of the development of a reporting guideline.
AB  - BACKGROUND: The aim of this systematic review was to identify which information
      is included when reporting educational interventions used to facilitate
      foundational skills and knowledge of evidence-based practice (EBP) training for
      health professionals. This systematic review comprised the first stage in the
      three stage development process for a reporting guideline for educational
      interventions for EBP. METHODS: The review question was 'What information has
      been reported when describing educational interventions targeting foundational
      evidence-based practice knowledge and skills?'MEDLINE, Academic Search Premier,
      ERIC, CINAHL, Scopus, Embase, Informit health, Cochrane Library and Web of
      Science databases were searched from inception until October - December 2011.
      Randomised and non-randomised controlled trials reporting original data on
      educational interventions specific to developing foundational knowledge and
      skills of evidence-based practice were included.Studies were not appraised for
      methodological bias, however, reporting frequency and item commonality were
      compared between a random selection of studies included in the systematic review
      and a random selection of studies excluded as they were not controlled trials.
      Twenty-five data items were extracted by two independent reviewers (consistency >
      90%). RESULTS: Sixty-one studies met the inclusion criteria (n = 29 randomised, n
      = 32 non-randomised). The most consistently reported items were the learner's
      stage of training, professional discipline and the evaluation methods used
      (100%). The least consistently reported items were the instructor(s) previous
      teaching experience (n = 8, 13%), and student effort outside face to face contact
      (n = 1, 2%). CONCLUSION: This systematic review demonstrates inconsistencies in
      describing educational interventions for EBP in randomised and non-randomised
      trials. To enable educational interventions to be replicable and comparable,
      improvements in the reporting for educational interventions for EBP are required.
      In the absence of a specific reporting guideline, there are a range of items
      which are reported with variable frequency. Identifying the important items for
      describing educational interventions for facilitating foundational knowledge and
      skills in EBP remains to be determined. The findings of this systematic review
      will be used to inform the next stage in the development of a reporting guideline
      for educational interventions for EBP.

PMID- 25060162
TI  - Brain organization and habitat complexity in Anolis lizards.
AB  - Across vertebrates, there is a broad correlation between neuroanatomy and the
      type of habitat preferred by a species. In general, species occupying habitats
      classified as more structurally complex have relatively larger brains and
      exaggerated structures related to navigating and exploiting those habitats. We
      empirically measured the structural habitat complexity of six species of Puerto
      Rican Anolis lizards, which have traditionally been classified as occupying three
      distinct habitat types. We also measured the volume of the whole brain as well as
      six structures putatively related to exploiting complex habitats in these
      species. We found a significant interspecific variation in structural habitat
      complexity, including a substantial variation between those belonging to the same
      ecomorph category. Despite this, we found no evidence to support the hypothesis
      that interspecific differences in habitat preferences, particularly differences
      in the relative structural complexity of those habitats, can favor a divergence
      in neuroanatomy. However, our findings indicate that, at a finer scale, species
      preferences for structural habitats vary greatly between Anolis species belonging
      to the same ecomorph category. This variation might contribute to the community
      structure of anoles by allowing multiple sympatric species of the same ecomorph
      category to occupy what, at a coarse scale, appears to be the same structural
      niche. We propose that, in the case of arboreal species, differences in the
      complexity of arboreal habitats alone may not be sufficient to favor divergent
      brain evolution.

PMID- 25060163
TI  - Development of a flow-injection analysis system with fluorescence detection for
      gatifloxacin determination in organized medium.
AB  - This work reports the development and optimization of a flow injection analysis
      system with fluorescence detection (FIA-FLUO) for gatifloxacin (GFX)
      determination in organized medium. The analytical system was based on the
      enhanced fluorescence of gatifloxacin in micellar medium containing sodium
      dodecyl sulfate (SDS) at pH 6.0. The influence of physical (carrier flow rate,
      sample volume and volume of reaction coil) and chemical (pH, concentration of
      buffer and concentration of SDS) parameters that could affect the performance of
      the FIA system was evaluated in order to reach optimum conditions in terms of
      sensitivity and analytical throughput. Under optimized conditions, the FIA-FLUO
      system allowed the injection of 40 samples per hour with a limit of
      quantification of 72 ug/L and a RSD of 3.5% at 0.20 mg/L. Real samples of
      commercial pharmaceutical formulations containing GFX were analyzed, and no
      statistical difference was observed between the results obtained using the
      developed system and those obtained using the reference method based on high
      performance liquid chromatography with UV detection.

PMID- 25060164
TI  - A minimum fluid volume of 75 mL is needed to ensure adequacy in a pleural
      effusion: a retrospective analysis of 2540 cases.
AB  - BACKGROUND: No consensus exists regarding minimum fluid volume for adequacy of
      benign pleural effusion specimens. Although any volume is acceptable if cytologic
      findings are malignant, the distinction between the absence of disease and false
      negativity is not straightforward in low-volume specimens. Recent literature has
      offered conflicting results regarding what minimum volume is necessary. Moreover,
      no studies to date have evaluated this issue across a large series of specimens
      with a wide distribution of volumes. The objective of the current study was to
      determine the minimum volume of pleural fluid necessary for optimal
      cytopathological diagnosis. METHODS: The authors identified 2540 pleural fluid
      specimens received between January 2000 and December 2009 and retrospectively
      reviewed their diagnoses and characteristics. Because of the large range of
      volumes (1 mL-6500 mL), the cases were binned into 9 groups of roughly equivalent
      sample sizes. The malignancy fractions (percentage of cases with malignant
      diagnoses) were compared for each group. RESULTS: The current study specimens had
      a median volume of 200 mL and an overall malignancy fraction of 20.1%. The
      malignancy fraction increased from 10.1% (95% confidence interval, 8.1%-12.1%)
      for volumes < 5 mL to 23.3% (95% confidence interval, 20.0%-25.8%) for volumes
      between 50 mL and 75 mL (P = .009). Specimens with volumes >= 75 mL had
      malignancy fractions independent of volume. In addition, ratios of benign or
      malignant diagnoses versus nondiagnostic and atypical results continued to
      increase with volume. CONCLUSIONS: A fluid volume of >= 75 mL is required to
      eliminate the influence of specimen size on diagnostic adequacy. Although larger
      volumes do not appear to impact malignancy fraction, they do correlate with
      decreased nondiagnostic and atypical results.

PMID- 25060165
TI  - The arrow-tipped loop is a marker of radiculomedullary vein thrombosis linked to
      the anti-reflux mechanism--angiographic anatomy and clinical implications.
AB  - INTRODUCTION: This article proposes that the "arrow-tipped" loop or anastomosis
      classically described as an anatomic variant represents in fact a pathological
      phenomenon resulting from the partial thrombosis of a radiculomedullary vein
      (RMV) with a duplicated origin (double-rooted RMVs). METHODS: The arrow-tip loop
      concept proposed in this report is illustrated with angiographic observations of
      patients with underlying pathologies of the spinal venous system, three cases of
      spinal arteriovenous fistulas, and one case of spinal venous insufficiency.
      RESULTS: In each clinical case, the presence of arrow-tip loops was associated
      with diffuse alteration of the perimedullary venous system, including the lack of
      detectable RMVs. The angiographic appearance of the arrow-tip loops suggested
      partially thrombosed double-rooted RMVs, with rootlets originating either from
      the anterior or posterior spinal veins, or from both. CONCLUSION: While a
      thrombosed single-rooted RMV typically becomes anatomically and angiographically
      undetectable, double-rooted MRVs keep a flowing proximal segment made of their
      two rootlets of origin. This residual proximal segment takes the appearance of an
      arrow-tip loop, which therefore be seen as an indicator of spinal venous
      thrombosis.

PMID- 25060166
TI  - Minimal hepatic encephalopathy in children with liver cirrhosis: diffusion
      weighted MR imaging and proton MR spectroscopy of the brain.
AB  - INTRODUCTION: The aim of this work was to detect minimal hepatic encephalopathy
      (minHE) in children with diffusion-weighted MR imaging (DWI) and proton magnetic
      resonance spectroscopy (1H-MRS) of the brain. METHODS: Prospective study
      conducted upon 30 consecutive children (age range 6-16 years, 21 boys and 9
      girls) with liver cirrhosis and 15 age- and sex-matched healthy control children.
      Patients with minHE (n = 17) and with no minHE (n = 13) groups and control group
      underwent DWI, 1H-MRS, and neuropsychological tests (NPTs). The glutamate or
      glutamine (Glx), myoinositol (mI), choline (Cho), and creatine (Cr) at the right
      ganglionic region were determined at 1H-MRS. The apparent diffusion coefficient
      (ADC) value and metabolic ratios of Glx/Cr, mI/Cr, and Cho/Cr were calculated.
      RESULTS: There was elevated ADC value and Glx/Cr and decreased mI/CI and Ch/Cr in
      patients with minHE compared to no minHE and control group. There was significant
      difference between minHE, no minHE, and control group in the ADC value (P = 0.001
      for all groups), GLx/Cr (P = 0.001 for all groups), mI/Cr (P = 0.004, 0.001, and
      0.001, respectively), Ch/Cr (P = 0.001 for all groups), and full-scale IQ of NPT
      (P = 0.001, 0.001, and 0.143, respectively). The NPT of minHE had negative
      correlation with ADC value (r = -0.872, P = 0.001) and GLx/Cr (r = -0.812, P =
      0.001) and positive correlation with mI/Cr (r = 0.732, P = 0.001). CONCLUSION:
      DWI and 1H-MRS are imaging modalities that can detect minHE in children with
      liver cirrhosis and correlate well with parameters of NPT.

PMID- 25060167
TI  - The severity of circulating neutrophil dysfunction in patients with cirrhosis is
      associated with 90-day and 1-year mortality.
AB  - BACKGROUND: Patients with cirrhosis are susceptible to sepsis, pre-disposing to
      the development of encephalopathy, bleeding and organ dysfunction with associated
      high mortality. AIM: To characterise circulating neutrophil function in a
      cirrhotic cohort as a determinant of 90-day and 1-year mortality. METHODS: Sixty
      two patients with cirrhosis [49 stable (Child-Pugh A/B/C = 24%/39%/37%); 13 acute
      on-chronic liver failure] were prospectively studied and compared with 11 healthy
      controls. Neutrophil function was evaluated at baseline and repeated at critical
      points during the course of the patient's illness until death/transplantation.
      Neutrophil phenotype was determined using fluorochrome-labelled antibodies to
      CD16/CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA)
      and capacity (NPC) were determined using FITC-labelled opsonised Escherichia
      coli. Oxidative burst (OB) was quantified by the percentage of neutrophils
      producing reactive oxygen species (ROS) and mean fluorescence intensity at rest,
      and after stimulation with E. coli. Physiological variables, biochemistry,
      microbiology and outcomes were collected. Plasma pro- and anti-inflammatory
      cytokine profiles were performed by ELISA. RESULTS: NPA/NPC was impaired in
      cirrhosis with the most significant dysfunction being observed in those with
      advanced disease and in those treated with propranolol. NPC predicted survival in
      stable cirrhosis [AUROC 0.83 (95% CI 0.68-0.97); P = 0.021] and differentiated
      survivors from nonsurvivors (90-day P = 0.01; 1 year P < 0.001). Resting OB >=12%
      predicted 90-day mortality with 80% sensitivity and 71% specificity [AUROC 0.81
      (95% CI 0.64-0.97); P = 0.026 and differentiated survivors from nonsurvivors; P =
      0.015]. CONCLUSION: Circulating neutrophils in patients with cirrhosis are
      dysfunctional and predict the development of infection, organ dysfunction and
      survival at 90 days and 1 year.

PMID- 25060168
TI  - Investigational drugs targeting somatostatin receptors for treatment of
      acromegaly and neuroendocrine tumors.
AB  - INTRODUCTION: Octreotide long-acting release (LAR) and lanreotide Autogel (ATG)
      are the two somatostatin analogs currently approved for treatment of acromegaly
      and neuroendocrine tumors (NETs). The strength of these drugs has been their
      specificity for somatostatin receptor subtype 2. However, this peculiarity may
      become a weakness in some patients with tumors harboring somatostatin receptors
      different from the subtype 2. Another clinically relevant aspect related to the
      use of octreotide LAR and lanreotide ATG is the burden of injectable drug regimen
      that may adversely impact the quality of life of patients with acromegaly and
      NETs. AREAS COVERED: The authors review the recently published evidence on novel
      drugs targeting somatostatin receptors developed for treating acromegaly and
      NETs. Within this article, the authors discuss: i) the pharmacology of
      somatostatin and traditional somatostatin analogs; ii) the efficacy and safety of
      multireceptor-targeted somatostatin analogs in acromegaly and NETs; iii) the
      efficacy of chimeric molecules in acromegaly and NETs; iv) the preliminary data
      on the use of new injectable, oral and transdermal formulations of octreotide in
      acromegaly. EXPERT OPINION: The development of new somatostatin analogs and new
      formulations has opened a new scenario for treatment of acromegaly and NETs. That
      being said, even though there have been big steps taken in the development of new
      therapies for acromegaly, there are still a number of unresolved issues, while
      more trials are necessary for the use of somatostatin anaologs in the treatment
      of NETs.

PMID- 25060172
TI  - Effects of essential oils, yeast culture and malate on rumen fermentation, blood
      metabolites, growth performance and nutrient digestibility of Baluchi lambs fed
      high-concentrate diets.
AB  - The experiment was conducted to evaluate the effects of dietary supplementation
      with a mixture of essential oils (MEO), yeast culture (YC) and malate on
      performance, nutrient digestion, rumen fermentation and blood metabolites of
      lambs fed high-concentrate growing diets. For this purpose, twenty Baluchi lambs
      (17.3 +/- 0.5 kg body weight and 3 months old) were randomly assigned to four
      dietary treatments in a completely randomized design with five lambs per
      treatment. The treatment groups were as follows: (i) control: basal diet without
      any additive, (ii) basal diet plus 400 mg/day MEO (thymol, carvacrol, eugenol,
      limonene and cinnamaldehyde), (iii) basal diet with 4 g/day YC and (iv) basal
      diet plus 4 g/day malate. No differences between the dietary treatments were
      observed in dry matter intake, average daily gain or feed conversion ratio (p >
      0.05). Compared with control and malate treatment, lambs fed MEO and YC had an
      improved crude protein digestibility (p < 0.05). Yeast culture significantly
      increased (p > 0.05) cell wall digestibility compared to the other treatments. No
      differences were observed between treatments with respect to nitrogen balance or
      ruminal pH and ammonia concentrations (p > 0.05). No differences were observed
      between treatments with respect to ruminal total volatile fatty acid
      concentration and molar proportions of acetate, butyrate and valerate. Molar
      proportion of propionate was higher (p < 0.05) for YC and malate compared to
      control and MEO. Plasma glucose concentration was higher (p < 0.05) in lambs fed
      YC and malate than in lambs fed the control or the MEO diet. Blood concentration
      of triglycerides significantly decreased when feeding the MEO and YC diets (p <
      0.05). It was concluded that YC may be more useful as a feed additive for
      manipulation of rumen fermentation in lambs fed with high-concentrate diets than
      MEO and malate, because YC enhanced crude protein and cell wall digestibility,
      ruminal molar proportion of propionate and plasma glucose concentration. 

PMID- 25060169
TI  - Mozart, music and medicine.
AB  - According to the first publication in 1993 by Rauscher et al. [Nature
      1993;365:611], the Mozart effect implies the enhancement of reasoning skills
      solving spatial problems in normal subjects after listening to Mozart's piano
      sonata K 448. A further evaluation of this effect has raised the question whether
      there is a link between music-generated emotions and a higher level of cognitive
      abilities by mere listening. Positron emission tomography and functional magnetic
      resonance imaging have revealed that listening to pleasurable music activates
      cortical and subcortical cerebral areas where emotions are processed. These
      neurobiological effects of music suggest that auditory stimulation evokes
      emotions linked to heightened arousal and result in temporarily enhanced
      performance in many cognitive domains. Music therapy applies this arousal in a
      clinical setting as it may offer benefits to patients by diverting their
      attention from unpleasant experiences and future interventions. It has been
      applied in the context of various important clinical conditions such as
      cardiovascular disorders, cancer pain, epilepsy, depression and dementia.
      Furthermore, music may modulate the immune response, among other things,
      evidenced by increasing the activity of natural killer cells, lymphocytes and
      interferon-gamma, which is an interesting feature as many diseases are related to
      a misbalanced immune system. Many of these clinical studies, however, suffer from
      methodological inadequacies. Nevertheless, at present, there is moderate but not
      altogether convincing evidence that listening to known and liked music helps to
      decrease the burden of a disease and enhances the immune system by modifying
      stress.

PMID- 25060174
TI  - An enzymatic approach to bifunctional chelating agents.
AB  - Bifunctional chelating agents (BFCAs) combine the complexing properties of a
      multidentate ligand with the presence of a free reactive functional group, mainly
      devoted to conjugation purposes. Indeed, products obtained by conjugation of a
      BFCA to a biomolecule and coordination of a suitable metal ion are widely applied
      in medicine nowadays as diagnostic and therapeutic agents. BFCAs are generally
      prepared through multi-step syntheses and with extensive application of
      protection-deprotection strategies, due to the large number of functional groups
      involved. Hydrolytic enzymes, with their unique chemoselectivity, provided the
      best results in the preparation of three different BFCAs based on very useful and
      well known ligand platforms. 

PMID- 25060173
TI  - Effect of deworming on school-aged children's physical fitness, cognition and
      clinical parameters in a malaria-helminth co-endemic area of Cote d'Ivoire.
AB  - BACKGROUND: Malaria and helminth infections are thought to negatively affect
      children's nutritional status and to impair their physical and cognitive
      development. Yet, the current evidence-base is weak. The purpose of this study
      was to determine the effect of deworming against soil-transmitted helminthiasis
      and schistosomiasis on children's physical fitness, cognition and clinical
      parameters in a malaria-helminth co-endemic setting of Cote d'Ivoire. METHODS: We
      designed an intervention study with a 5-month follow-up among schoolchildren aged
      5-14 years from Niable, eastern Cote d'Ivoire. In late 2012, a baseline cross
      sectional survey was conducted. Finger-prick blood, stool and urine samples were
      subjected to standardised, quality-controlled techniques for the diagnosis of
      Plasmodium spp., Schistosoma spp., soil-transmitted helminths and intestinal
      protozoa infections. Haemoglobin level was determined and anthropometric
      measurements were taken for appraisal of anaemia and nutritional status. Children
      underwent memory (digit span) and attention (code transmission) cognitive
      testing, and their physical fitness and strength were determined (20 m shuttle
      run, standing broad jump and grip strength test). All children were treated with
      albendazole (against soil-transmitted helminthiasis) and praziquantel (against
      schistosomiasis) after the baseline cross-sectional survey and again 2 months
      later. Five months after the initial deworming, the same battery of clinical,
      cognitive and physical fitness tests was performed on the same children. RESULTS:
      Lower scores in strength tests were significantly associated with children with
      harbouring nutritional deficiencies. Surprisingly, boys infected with Schistosoma
      mansoni achieved longer jumping distances than their non-infected counterparts.
      Light-intensity infection with S. mansoni was associated with slightly better
      aerobic capacity. Deworming showed no effect on haemoglobin levels and anaemia,
      but children with moderate- to heavy-intensity Schistosoma infection at baseline
      gained weight more pronouncedly than non-infected children. Interestingly,
      children with soil-transmitted helminth or Schistosoma infection at baseline
      performed significantly better in the sustained attention test than their non
      infected counterparts at the 5-month follow-up. CONCLUSIONS: This study revealed
      conflicting results regarding clinical parameters and cognitive behaviour of
      children after two rounds of deworming. We speculate that potential beneficial
      effects of deworming are likely to be undermined in areas where malaria is co
      endemic and nutritional deficiencies are widespread.

PMID- 25060175
TI  - New possibilities for volumetric-modulated arc therapy using the AgilityTM 160
      leaf multileaf collimator.
AB  - PURPOSE: This study compares the quality of intensity-modulated radiotherapy
      (IMRT) and volumetric-modulated arc therapy (VMAT) plans optimized for an Elekta
      Agility(TM) (Elekta, Stockholm, Sweden) multileaf collimator (MLC; leaf width 5
      mm) and an Elekta MLCi2 (leaf width 10 mm) for complex target volumes (anal, AC;
      head and neck, H&N and prostate cancer, PC). PATIENTS AND METHODS: For plan
      comparisons, 15 patients who had been treated with IMRT or VMAT using the MLCi2
      were selected. For each patient, a retrospective treatment plan using the MLCi2
      for the technique not applied was created, as were treatment plans for both
      techniques using the Agility(TM) MLC. Dose-volume histograms (DHVs) for planning
      target volumes (PTVs) and organs at risk (OARs) were compared. Further parameters
      relating to dose conformity, dose homogeneity and mean dose (Dmean) to the PTV,
      compliance with the intended OAR dose criteria and overall dose to normal tissue
      were analyzed. Verification measurements were performed and optimization and
      treatment times were compared. RESULTS: Compared to the MLCi2 plans, the
      Agility(TM) IMRT and VMAT plans show better or equivalent results in terms of PTV
      dose conformity and homogeneity. Compliance with the intended OAR dose criteria
      does not differ according to technique or MLC type. Slight differences are shown
      for dose distributions in OARs and normal tissue. Verification measurements show
      that all plans fulfill the acceptance criteria of a minimum of 95 % matched dose
      points for the 3 %/3 mm gamma criterion. Optimization times for the VMAT plans
      increase compared to the IMRT plans, whereas treatment times decrease.
      CONCLUSION: With the MLCi2, treatment of complex target volumes with VMAT was
      only possible with compromises in terms of target coverage. Using the Agility(TM)
      MLC, even complex target volumes can be treated with VMAT without compromising
      target coverage or resulting in higher exposure of OARs or normal tissue.

PMID- 25060176
TI  - Kasabach-Merritt phenomenon in hepatic angiosarcoma.

PMID- 25060177
TI  - Serum CCL2 and CCL3 as potential biomarkers for the diagnosis of oral squamous
      cell carcinoma.
AB  - Monocyte chemotactic protein-1 (MCP-1/CCL2) and macrophage inflammatory protein
      1alpha (MIP-1alpha/CCL3) are small chemotactic proteins that have been found in
      several kinds of tumor tissue samples and function as key regulators of cancer
      progression. However, the expression of CCL2 and CCL3 in serum samples of oral
      squamous cell carcinoma (OSCC) patients remains unknown. This study aimed to
      investigate the prognostic meaning of serum CCL2 and CCL3 in OSCC. The
      concentration of CCL2 and CCL3 was assessed by ELISA in serum of OSCC patients (n
      = 98), leukoplakia patients (n = 14), and healthy donors (n = 27). The results
      showed that the concentration of CCL2 in the OSCC group was significantly lower
      compared to that in the healthy controls (67.81 vs. 108.1 pg/ml, P < 0.0001). The
      CCL3 concentration was higher in leukoplakia patients than in OSCC patients and
      healthy donors (201.9 vs. 153.9 or 118.3 pg/ml, P < 0.05). No significant
      difference in CCL3 concentration was observed between OSCC patients and healthy
      donors. However, the OSCC group clearly presented two subclusters, i.e., CCL3
      (LOW) and CCL3 (HIGH) OSCC subclusters, in which the serum level of CCL3 was
      positively related to the tumor size. Interestingly, the ratio of CCL2/CCL3 in
      OSCC patients was correlated to TNM (tumor, node, metastasis), smoking habits,
      and differentiation. The receiver operating characteristic (ROC) curve suggests
      that serum CCL2 is a good diagnostic marker to discriminate OSCC patients from
      healthy people (cutoff value, 101.1 pg/ml) and the ratio of CCL2/CCL3 also is a
      good diagnostic marker to discriminate leukoplakia patients and CCL3 (HIGH) OSCC
      patients from healthy people (cutoff values, 1.080 and 0.424, respectively).
      These results indicate that CCL2 and CCL3 are associated with progression of OSCC
      and may be potential biomarkers.

PMID- 25060178
TI  - The combination of a nuclear HMGB1-positive and HMGB2-negative expression is
      potentially associated with a shortened survival in patients with pancreatic
      ductal adenocarcinoma.
AB  - High-mobility group box (HMGB) proteins are ubiquitous, abundant nuclear non
      histone chromosomal proteins that play a critical role in binding to distorted
      DNA structures and subsequently regulating DNA transcription, replication,
      repair, and recombination. Both HMGB1 and HMGB2 exhibit a high expression in
      several human cancers and are closely associated with tumor progression and a
      poor prognosis. However, the expression patterns of these molecules in pancreatic
      ductal adenocarcinoma (PDAC) remain to be elucidated. As most cases of
      postoperative relapse of PDAC occur within the first 2 years, the clinical
      significance of accurate biomarkers is needed. Therefore, we investigated the
      correlation between the immunohistochemical HMGB1 and HMGB2 expression and the
      clinicopathological characteristics and prognosis using 62 paraffin-embedded
      tumor samples obtained from patients with surgically resected PDAC. The HMGB1/2
      expression was considered to be positive when 10 % or more of the cancer cells
      showed positive nuclear, not merely cytoplasmic, staining. Consequently, the
      expression of HMGB1/2 was observed in 54 (87.1 %) and 31 (50.0 %) patients,
      respectively. Unexpectedly, a positive HMGB1 expression was found to have a
      significantly close relationship with a negative HMGB2 expression. The univariate
      and multivariate analyses demonstrated that the patients with a HMGB1+ and HMGB2-
      status had markedly lower disease-specific survival rates, especially within the
      first 2 years postoperatively, whereas those with a HMGB1+ status alone did not.
      Therefore, the combination of a HMGB1+ and HMGB2- expression potentially predicts
      a poor prognosis in patients with PDAC, and these new biomarkers may be useful
      parameters for clinical management in the early postoperative phase.

PMID- 25060179
TI  - Relationship of serum MMP-7 levels for colorectal cancer: a meta-analysis.
AB  - This meta-analysis aimed to identify the value of serum matrix metalloproteinase
      7 (MMP-7) levels for the diagnosis of colorectal cancer (CRC). Through searching
      the following electronic databases: Cochrane Library (Issue 12, 2014), Web of
      Science (1945~2014), PubMed (1966~2014), CINAHL (1982~2014), EMBASE (1980~2014),
      and CBM (1982~2014), related articles were determined without any language
      restrictions. Stata statistical software (Version 12.0, Stata Corporation,
      College Station, TX, USA) was chosen to deal with statistical data. Standard mean
      difference (SMD) and its corresponding 95 % confidence interval (95 % CI) were
      calculated to clarify the correlation between serum MMP-7 levels and CRC. Seven
      clinical case-control studies which recruited 430 CRC patients and 357 healthy
      subjects were selected for statistical analysis. The main findings of our meta
      analysis showed that the serum MMP-7 level in CRC patients was significantly
      higher than that in control subjects (SMD = 2.15, 95 % CI = 1.46~2.84, P <
      0.001). Ethnicity-stratified analysis indicated a higher serum MMP-7 level in CRC
      patients than that of control subjects among the Asians and the Caucasians
      (Asians: SMD = 2.83, 95 % CI = 1.76~3.91, P < 0.001; Caucasians: SMD = 1.06, 95 %
      CI = 0.46~1.66, P = 0.001; respectively). The present meta-analysis indicated
      that the increased serum level of MMP-7 may be connected with the development of
      CRC; thus, serum levels of MMP-7 could be an independent biomarker for CRC
      patients.

PMID- 25060180
TI  - Diagnostic performance of microRNAs expression in prostate cancer.
AB  - MicroRNAs (miRNAs) have been proposed as ideal diagnostic indicators of prostate
      cancer (CaP). However, previous studies have reported conflicting results.
      Therefore, we conducted this meta-analysis to assess the potential diagnostic
      value of miRNAs for CaP. A systematic literature search was conducted in PubMed
      and other databases. Results from different studies were pooled using random
      effects models. The pooled sensitivity (SEN), specificity (SPE), positive and
      negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio
      (DOR), and area under the curve (AUC) were calculated to evaluate the overall
      test performance. Between-study heterogeneity was tested using the chi-squared
      test and the I (2) test. Meta-regression and subgroup analyses were performed to
      explore the potential sources of heterogeneity. Fifty-eight studies from ten
      articles, including 669 patients with CaP and 404 controls composed of healthy
      individuals and patients with benign prostatic hyperplasia (BPH), were included
      in this meta-analysis. The pooled SEN and SPE were 0.74 (95 % confidence interval
      (CI) 0.70-0.78) and 0.73 (95 % CI 0.70-0.76), respectively. The pooled PLR was
      2.7 (95 % CI 2.4-3.1); NLR was 0.35 (95 % CI 0.30-0.42); and DOR was 8 (95 % CI 6
      10). The pooled AUC was 0.79 (95 % CI 0.76-0.83). Subgroup analyses indicated
      that multiple miRNAs yielded a better diagnostic accuracy. This systematic review
      suggests that miRNA analysis can significantly improve the overall accuracy of
      CaP diagnosis. Moreover, using multiple miRNA-based assays could achieve
      significantly higher accuracy in diagnosing CaP than single miRNA-based assays.

PMID- 25060181
TI  - Combined use of lysyl oxidase, carcino-embryonic antigen, and carbohydrate
      antigens improves the sensitivity of biomarkers in predicting lymph node
      metastasis and peritoneal metastasis in gastric cancer.
AB  - The purpose of this study was to determine whether lysyl oxidase (LOX) is a
      useful marker of metastasis in gastric cancer (GC) patients in combination with
      tumor markers carcino-embryonic antigen (CEA), carbohydrate antigen 724 (CA724),
      carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125). There
      were 215 GC patients (67 without metastasis, 102 with lymph node metastasis, and
      46 with peritoneal metastasis) who presented to the Affiliated Cancer Hospital of
      Guangxi Medical University between May 2009 and November 2012 that were enrolled
      in this study. The LOX expression level and the serum concentration of the four
      tumor markers were evaluated preoperatively. All patients underwent computed
      tomography (CT) and ultrasonography (US) before surgery. Statistical analysis,
      including receiver operating characteristic (ROC) curve analysis, area under the
      curve (AUC) analysis, and logistic regression analysis, was performed to evaluate
      the diagnostic value of these markers in predicting metastasis in GC. For
      predicting lymph node metastasis in GC, the sensitivity of LOX, CEA, CA724,
      CA199, and CA125 was 44.12, 12.75, 21.57, 23.53, and 15.69 %, respectively, and
      increased to 79.41 % in combination. For predicting peritoneal metastasis in GC,
      the sensitivity of these markers was 56.52, 23.91, 34.78, 36.96, and 34.78 %,
      respectively, and increased to 91.30 % in combination. Combining LOX with CEA,
      CA724, CA199, and CA125 could increase the sensitivity of predicting lymph nodes
      metastasis and peritoneal metastasis in GC. Surgeons can use these markers to
      determine the best treatment options for patients. Additional large-scale,
      prospective, multicenter studies are urgently needed to further confirm the
      results of this study.

PMID- 25060182
TI  - Expression and clinical significance of Shh/Gli-1 in papillary thyroid carcinoma.
AB  - The Sonic Hedgehog (Shh) pathway affects cancer initiation, progression, and
      metastasis, but its role in papillary thyroid carcinoma (PTC) remains elusive. To
      characterize expression and clinical significance of Shh and the transcription
      factor Gli-1-the key elements of the Shh pathway in PTC tissues-we
      immunohistochemically examined Shh/Gli-1 expression in PTC tissues from 142
      patients, along with adjacent non-cancerous tissues as controls. We reviewed 142
      patients' clinical characteristics and analyzed their relationship with
      expression of Shh/Gli-1. Shh and Gli-1 were expressed in 64.1 % (91/142) and 47.9
      % (68/142) in PTC tissues, respectively, compared with 16.9 % (24/142) and 9.2 %
      (13/142) of adjacent non-cancerous tissues. Gli-1 expression was significantly
      associated with patients' ages (P < 0.05) and lymph node metastasis (P < 0.01).
      Increased Shh and Gli-1 expression was significantly associated with tumor-node
      metastasis (TNM) stage (P < 0.01). Shh and Gli-1 were expressed in 79.2 and 60.4
      %, respectively, of PTC tumors larger than 10 mm. Shh was significantly
      associated with tumor size (P < 0.01). Shh and Gli-1 were expressed in 72.5 and
      65.2 %, respectively, of patients with lymph node metastasis. Overall, we found
      increased expression of the main initiator Shh and transcription factor Gli-1 in
      Shh pathway in PTC tissues. The expression of Shh/Gli-1 was significantly
      associated with tumor size, clinical staging, and lymph node metastasis,
      indicating that aberrant activation of the Shh pathway is important to PTC
      occurrence and progression. Potentially, Shh/Gli-1 could be a diagnostic
      indicator and a marker of therapeutic response.

PMID- 25060183
TI  - Expression of estrogen receptors alpha and beta in the trigeminal mesencephalic
      nucleus of adult women and men.
AB  - Temporomandibular disorders are more prevalent in women than in men and phases of
      pain relate to the estrous cycle. Several studies described the location of
      estrogen receptors (ER) in the temporomandibular joint (TMJ), the masseteric
      muscles and cartilage, but it was unknown whether they are also expressed within
      the pseudounipolar neurons of the trigeminal mesencephalic nucleus, which
      receives direct sensory inputs from these structures. Therefore, we studied
      expression of ERalpha and ERbeta protein in the trigeminal mesencephalic nucleus
      of ten human brains (five female/five male). Both receptors were uniformly
      expressed on neurons, but not other cell types within the target structure. Thus,
      sensory inputs from the TMJ and adjacent structures are likely to be modulated by
      estrogen at the level of the first sensory neuron which may underlie the well
      known correlation of pain incidence and phases of the estrous cycle.

PMID- 25060184
TI  - Aggressive primary thyroid lymphoma: imaging features of two elderly patients.
AB  - We report two cases of aggressive thyroid lymphoma in elderly patients that
      presented as Epub ahead of print large infiltrative thyroid masses with extensive
      invasion to adjacent structures including trachea, esophagus, and common carotid
      artery. Ultrasonography displayed irregular shaped, heterogeneous hypoechoic
      mass, mimicking anaplastic carcinoma. Computed tomography showed heterogeneously
      enhancing mass compared to surrounding muscles without calcification and
      hemorrhage. After biopsy, the masses were histopathologically diagnosed as
      lymphoma. Aggressive primary thyroid lymphoma is rare; therefore, here we report
      its image features, with emphasis on ultrasonographic findings, and discuss its
      differential diagnosis. 

PMID- 25060185
TI  - Harmonic ultrasonography for the detection of microlithiasis in the gallbladder.
AB  - PURPOSE: To validate the use of harmonic ultrasonography (US) in the detection of
      gallbladder microlithiasis. METHODS: From November 30, 2012, to January 18, 2014,
      fundamental US (FUS) and harmonic US with a high background noise (HUS-N) were
      performed for evaluation of gallbladder during the routine abdomen US. During the
      US, a dot-like stone (or stones) with Brownian motion was regarded as a positive
      finding of microlithiasis. Fifty-five patients with microlithiasis in the
      gallbladder detected on US were enrolled as the subjects of a retrospective
      review. With respect to the obtained images, two abdominal radiologists
      independently scored the conspicuity of gallbladder microlithiasis on FUS and HUS
      N by using a 4-grade scale. The statistical analysis employed a kappa test and a
      Wilcoxon rank-sum test. RESULTS: For FUS, the conspicuity grades of gallbladder
      microlithiasis were G1 in 25 and 37, G2 in 21 and 9, G3 in 6 and 6, G4 in 3 and 3
      patients, while HUS-N showed G1 in 0 and 0, G2 in 3 and 2, G3 in 12 and 15, and
      G4 in 40 and 38 patients, respectively, by each of the two radiologists. The
      kappa value was 0.633 for FUS between the two radiologists and 0.708 for HUS-N.
      HUS-N showed better conspicuity of gallbladder microlithiasis than FUS with
      significant P-values of less than 0.001 and 0.001 for the two radiologists,
      respectively. CONCLUSION: Compared with FUS, HUS-N enables better detection of
      microlithiasis in the gallbladder.

PMID- 25060186
TI  - Potential cost-shifting and hidden costs and risks in the economic analysis of
      opioid abuse-deterrent formulations.

PMID- 25060188
TI  - A step forward for self-management in chronic obstructive pulmonary disease.

PMID- 25060187
TI  - TITAN: inference of copy number architectures in clonal cell populations from
      tumor whole-genome sequence data.
AB  - The evolution of cancer genomes within a single tumor creates mixed cell
      populations with divergent somatic mutational landscapes. Inference of tumor
      subpopulations has been disproportionately focused on the assessment of somatic
      point mutations, whereas computational methods targeting evolutionary dynamics of
      copy number alterations (CNA) and loss of heterozygosity (LOH) in whole-genome
      sequencing data remain underdeveloped. We present a novel probabilistic model,
      TITAN, to infer CNA and LOH events while accounting for mixtures of cell
      populations, thereby estimating the proportion of cells harboring each event. We
      evaluate TITAN on idealized mixtures, simulating clonal populations from whole
      genome sequences taken from genomically heterogeneous ovarian tumor sites
      collected from the same patient. In addition, we show in 23 whole genomes of
      breast tumors that the inference of CNA and LOH using TITAN critically informs
      population structure and the nature of the evolving cancer genome. Finally, we
      experimentally validated subclonal predictions using fluorescence in situ
      hybridization (FISH) and single-cell sequencing from an ovarian cancer patient
      sample, thereby recapitulating the key modeling assumptions of TITAN. 

PMID- 25060189
TI  - Evaluation of a community-based participatory farmworker eye health intervention
      in the "black dirt" region of New York state.
AB  - BACKGROUND: Eye irritation is a constant hazard for migrant and seasonal
      farmworkers, but there are few studies of the problem or how to address it.
      Researchers evaluated the effect of a community-based participatory eye health
      intervention on farmworker eye symptoms in the Hudson Valley, NY. METHODS: A
      randomized pre-post intervention with 2, 4-week follow-up periods was implemented
      with a sample of 97 farmworkers. Five eye symptoms were measured, along with
      utilization of protective eyewear and eye drops. RESULTS: Leading baseline eye
      symptoms were redness (49%), blurred vision (43%), itching (43%), and eye pain
      (29%). Significant reductions in eye pain (P = 0.009), and non-significant
      reductions in redness were observed for the intervention group while controls
      experienced increases in both. CONCLUSIONS: The intervention was effective in
      significantly reducing eye pain, and to a lesser extent, redness. Future eyewear
      promotion programs should offer a range of eye wear, tailor offerings to local
      climate and tasks, evaluate eyewear durability, and include eye drops.

PMID- 25060190
TI  - Incidence of acetylcholine receptor-antibody-positive myasthenia gravis in South
      Africa.
AB  - INTRODUCTION: The aim of this study was to assess age- and gender-specific
      incidence rates (IRs) of acetylcholine receptor (AChR)-antibody-positive
      myasthenia gravis (MG) in South Africa, and geographical variations in incidence.
      METHODS: IRs were calculated from positive AChR-antibody laboratory data between
      2011 and 2012, using 2011 population census data. RESULTS: 890 individuals were
      seropositive, for an annual IR of 8.5 per million. Age-standardized IR for early
      onset (<50) and late-onset (>=50) MG were 4.1 and 24 per million, respectively,
      and 4.3 per million for juveniles. The IR between provinces ranged from 1 to 19
      per million. CONCLUSIONS: In this Southern Hemisphere African population, the
      overall IR and peak IR (in older men) for seropositive MG is comparable to that
      in Europe and North America, arguing against environmental factors. However, IRs
      may be higher among children with African genetic ancestry. Geographical
      variation in incidence underscores the importance of outreach programs for
      regions with limited resources.

PMID- 25060191
TI  - Kinetic mechanism of putrescine oxidase from Rhodococcus erythropolis.
AB  - Putrescine oxidase from Rhodococcus erythropolis (PuO) is a flavin-containing
      amine oxidase from the monoamine oxidase family that performs oxidative
      deamination of aliphatic diamines. In this study we report pre-steady-state
      kinetic analyses of the enzyme with the use of single- and double-mixing stopped
      flow spectroscopy and putrescine as a substrate. During the fast and irreversible
      reductive half-reaction no radical intermediates were observed, suggesting a
      direct hydride transfer from the substrate to the FAD. The rate constant of
      flavin reoxidation depends on the ligand binding; when the imine product was
      bound to the enzyme the rate constant was higher than with free enzyme species.
      Similar results were obtained with product-mimicking ligands and this indicates
      that a ternary complex is formed during catalysis. The obtained kinetic data were
      used together with steady-state rate equations derived for ping-pong, ordered
      sequential and bifurcated mechanisms to explore which mechanism is operative. The
      integrated analysis revealed that PuO employs a bifurcated mechanism due to
      comparable rate constants of product release from the reduced enzyme and
      reoxidation of the reduced enzyme-product complex.

PMID- 25060192
TI  - AtMYB41 activates ectopic suberin synthesis and assembly in multiple plant
      species and cell types.
AB  - Suberin is a lipid and phenolic cell wall heteropolymer found in the roots and
      other organs of all vascular plants. Suberin plays a critical role in plant water
      relations and in protecting plants from biotic and abiotic stresses. Here we
      describe a transcription factor, AtMYB41 (At4g28110), that can activate the steps
      necessary for aliphatic suberin synthesis and deposition of cell wall-associated
      suberin-like lamellae in both Arabidopsis thaliana and Nicotiana benthamiana.
      Overexpression of AtMYB41 increased the abundance of suberin biosynthetic gene
      transcripts by orders of magnitude and resulted in the accumulation of up to 22
      times more suberin-type than cutin-type aliphatic monomers in leaves.
      Overexpression of AtMYB41 also resulted in elevated amounts of monolignols in
      leaves and an increase in the accumulation of phenylpropanoid and lignin
      biosynthetic gene transcripts. Surprisingly, ultrastructural data indicated that
      overexpression led to the formation of suberin-like lamellae in both epidermal
      and mesophyll cells of leaves. We further implicate AtMYB41 in the production of
      aliphatic suberin under abiotic stress conditions. These results provide insight
      into the molecular-genetic mechanisms of the biosynthesis and deposition of a
      ubiquitous cell wall-associated plant structure and will serve as a basis for
      discovering the transcriptional network behind one of the most abundant lipid
      based polymers in nature. 

PMID- 25060193
TI  - Implications of revised AASM rules on scoring apneic and hypopneic respiratory
      events in heart failure patients with nocturnal Cheyne-Stokes respiration.

PMID- 25060194
TI  - Is radiocholine PET/CT already clinically useful in patients with prostate
      cancer?

PMID- 25060195
TI  - In vivo evaluation of angiogenic activity and its correlation with efficacy of
      indirect revascularization surgery in pediatric moyamoya disease.
AB  - Indirect revascularization is the most widely used treatment to induce
      angiogenesis in pediatric moyamoya disease (MMD). Molecular imaging methods
      targeted for angiogenesis have recently been developed. We performed angiogenesis
      imaging in indirect revascularization surgery for MMD to evaluate angiogenic
      activity and its correlation with treatment efficacy. METHODS: Twelve patients
      with pediatric MMD were prospectively enrolled. Encephaloduroarteriosynangiosis
      surgery was conducted, and (68)Ga-Arg-Gly-Asp (RGD) PET was performed 3.7 +/- 1.0
      mo after surgery. Basal perfusion and stress perfusion (PStr) in the middle
      cerebral artery territory were evaluated by acetazolamide-stress brain perfusion
      SPECT using statistical probabilistic anatomic mapping, at preoperative, early
      postoperative, and long-term follow-up states. Angiogenic activity was assessed
      on the images in terms of maximal uptake ratio, volume of increased uptake, and
      uptake-volume product. RESULTS: Basal perfusion and PStr were significantly
      improved after surgery. Increased angiogenic activity was observed in the
      revascularized area, mainly around the bony flap. Angiogenic activity gradually
      decreased with time and significantly correlated with the postoperative time
      interval (P = 0.0015 for maximal uptake ratio and 0.0069 for volume of increased
      uptake). It was estimated to normalize at 6.3 mo after surgery. Uptake-volume
      product was inversely correlated with PStr improvement at the early postoperative
      state (r = -0.5960, P = 0.0409) and also weakly correlated with PStr improvement
      at long-term follow-up (r = -0.5010, P = 0.1165). CONCLUSION: Angiogenesis PET
      imaging with (68)Ga-RGD was successfully used for the assessment of angiogenic
      activity in indirect revascularization surgery for MMD, and angiogenic activation
      measured at approximately 3.7 mo after surgery was inversely correlated with
      perfusion improvement. The assessment of angiogenic activity using (68)Ga-RGD PET
      is expected to be effective for evaluating the mechanism or efficacy of
      revascularization treatment.

PMID- 25060197
TI  - Fluorescence correlation spectroscopy at micromolar concentrations without
      optical nanoconfinement.
AB  - Fluorescence correlation spectroscopy (FCS) is an important technique for
      studying biochemical interactions dynamically that may be used in vitro and in
      cell-based studies. It is generally claimed that FCS may only be used at nM
      concentrations. We show that this general consensus is incorrect and that the
      limitation to nM concentrations is not fundamental but due to detector limits as
      well as laser fluctuations. With a high count rate detector system and applying
      laser fluctuation corrections, we demonstrate FCS measurements up to 38 MUM with
      the same signal-to-noise as at lower concentrations. Optical nanoconfinement
      approaches previously used to increase the concentration range of FCS are not
      necessary, and further increases above 38 MUM may be expected using detectors and
      detector arrays with higher saturation rates and better laser fluctuation
      corrections. This approach greatly widens the possibilities of dynamic
      measurements of biochemical interactions using FCS at physiological
      concentrations. 

PMID- 25060196
TI  - A modular labeling strategy for in vivo PET and near-infrared fluorescence
      imaging of nanoparticle tumor targeting.
AB  - Advances in preclinical molecular imaging have generated new opportunities to
      noninvasively visualize the biodistribution and tumor targeting of nanoparticle
      therapeutics. Capitalizing on recent achievements in this area, we sought to
      develop an (89)Zr-based labeling strategy for liposomal nanoparticles that
      accumulate in tumors via passive targeting mechanisms. METHODS: (89)Zr-labeled
      liposomes were prepared using 2 different approaches: click labeling and surface
      chelation. Pharmacokinetic and biodistribution studies, as well as PET/CT imaging
      of the radiolabeled nanoparticles, were performed on a mouse model of breast
      cancer. In addition, a dual PET/optical probe was prepared by incorporation of a
      near-infrared fluorophore and tested in vivo by PET and near-infrared
      fluorescence imaging. RESULTS: The surface chelation approach proved to be
      superior in terms of radiochemical yield and stability, as well as in vivo
      performance. Accumulation of these liposomes in tumor peaked at 24 h after
      injection and was measured to be 13.7 +/- 1.8 percentage injected dose per gram.
      The in vivo performance of this probe was not essentially perturbed by the
      incorporation of a near-infrared fluorophore. CONCLUSION: We have developed a
      highly modular and efficient strategy for the labeling of liposomal nanoparticles
      with (89)Zr. In xenograft and orthotopic mouse models of breast cancer, we
      demonstrated that the biodistribution of these nanoparticles can be visualized by
      PET imaging. In combination with a near-infrared dye, these liposomal
      nanoparticles can serve as bimodal PET/optical imaging agents. The liposomes
      target malignant growth, and their bimodal features may be useful for
      simultaneous PET and intraoperative imaging.

PMID- 25060198
TI  - Takotsubo cardiomyopathy: the challenging diagnosis in clinical routine.
AB  - Takotsubo cardiomyopathy is rapidly reversible heart failure syndrome that
      usually mimics the symptoms of acute myocardial infarction with the
      characteristic regional wall-motion abnormalities (classically with a virtual
      apical ballooning caused by hypokinetic or akinetic apical or midventricular
      myocardium and hypercontraction of the basal segments) and absence of obstructive
      coronary artery disease. TC is usually associated with identifiable emotional,
      psychological or physical stress event and most commonly appears in
      postmenopausal women. The certain pathophysiological mechanism remains unknown.
      However, the central hypothesis is supported by the excess of catecholamines and
      hyperactivity of nervous system. In the last decades the frequency of the TC
      diagnosis is increasing rapidly but at the initial presentation the diagnosis
      remains challenging due to the close similarities between TC and ST elevation
      myocardial infarction clinical presentations that consider TC as an important
      part of differential diagnosis in acute coronary syndrome. 

PMID- 25060199
TI  - Pepsinogen testing for evaluation of the success of Helicobacter pylori
      eradication at 4 weeks after completion of therapy.
AB  - BACKGROUND AND OBJECTIVE: Pepsinogen levels in plasma are increased by
      inflammation in the gastric mucosa, including inflammation resulting from
      Helicobacter pylori infection. A decrease in pepsinogen II level has been
      suggested as a reliable marker to confirm the successful eradication of
      infection. The aim of our study was to evaluate the potential role of pepsinogens
      I and II, gastrin-17 and H. pylori antibodies in confirming successful
      eradication. MATERIAL AND METHODS: Altogether 42 patients (25 women, 17 men),
      mean age 45 years (range 23-74), were enrolled. Pepsinogens I and II, gastrin-17
      and H. pylori IgG antibodies were measured in plasma samples using an ELISA test
      (Biohit, Oyj., Finland) before the eradication and 4 weeks after completing the
      treatment. The success of eradication was determined by a urea breath test.
      RESULTS: Eradication was successful in 31 patients (74%) and unsuccessful in 11
      patients (26%). Pepsinogen II decreased significantly in both the successful
      (P=0.029) and unsuccessful (P=0.042) eradication groups. Pepsinogen I decreased
      significantly in the successful (P=0.025) but not the unsuccessful (P=0.29)
      eradication group. The pepsinogen I/II ratio increased in the successful
      eradication group (P=0.0018) but not in the group in which treatment failed
      (P=0.12). There were no differences in gastrin-17 or H. pylori antibody values.
      CONCLUSIONS: A decrease in pepsinogen II levels cannot be used as a reliable
      marker for the successful eradication of H. pylori 4 weeks after the completion
      of treatment. The increase in pepsinogen I/II ratio reflects differences in
      pepsinogen production following the eradication irrespective of improvement in
      atrophy.

PMID- 25060200
TI  - NOTCH1, NOTCH3, NOTCH4, and JAG2 protein levels in human endometrial cancer.
AB  - BACKGROUND AND OBJECTIVE: Notch signaling is a conserved developmental pathway,
      which plays an important role in the regulation of cell proliferation,
      differentiation and death. Deregulation of Notch pathway has been connected with
      the carcinogenesis in a variety of cancers. The aim of this study was to
      investigate the level of the Notch signaling pathway proteins (NOTCH1, 3, 4 and
      JAG2) in the samples from human endometrial cancer. MATERIALS AND METHODS: The
      amount of the Notch receptors NOTCH1, 3, 4 and ligand JAG2 protein was determined
      by Western blot analysis in the samples from stage I endometrial cancer and
      adjacent nontumor endometrial tissue of 22 patients. RESULTS: The level of NOTCH4
      receptor was 1.7 times lower in stage I endometrial cancer as compared with the
      healthy tissue of the same patients (P=0.04). The protein level of ligand JAG2
      was significantly reduced by 2.5 times in stage IB endometrial adenocarcinoma
      samples (P=0.01). It was reduced in the majority of stage IB adenocarcinomas.
      There were no significant changes in the protein amount of NOTCH1 and NOTCH3
      receptors comparing stage I endometrial adenocarcinoma and healthy tissues.
      CONCLUSIONS: The reduced amount of NOTCH4 and JAG2 proteins and the decreased
      level of mRNA coding Notch proteins, as reported in our previous studies,
      supports the notion that Notch pathway has rather tumor-suppressive than
      oncogenic role in human endometrial cancer cells. It suggests that Notch pathway
      activation is a potential therapeutic target.

PMID- 25060201
TI  - Role of genetic factors on the effect of additional loading doses and two
      maintenance doses used to overcome clopidogrel hyporesponsiveness.
AB  - BACKGROUND AND OBJECTIVE: Additional loading doses and higher maintenance doses
      (MDs) have been used to overcome hyporesponsiveness of clopidogrel. We aimed to
      investigate whether genetic polymorphisms of two cytochromes (CYP2C19 and CYP2C9)
      and ABCB1 modify effect of such dose-adjustment strategy. MATERIALS AND METHODS:
      We enrolled 118 patients undergoing elective or acute percutaneous coronary
      intervention (PCI) with drug eluting stent (DES). Platelet reactivity index (PRI)
      was measured using the vasodilator-stimulated phosphoprotein (VASP) index and a
      cut-off value of >= 60% was defined as hyporesponsiveness. Polymorphism of two
      cytochromes (CYP2C19, CYP2C9) and gene ABCB1 were determined. In patients
      hyporesponsive to the initial LD the dose-adjustment was performed using up to 3
      additional 600 mg LDs in order to achieve PRI <60%, and both 150 mg and 75 mg MD
      were tested at the follow-up. RESULTS: Patients with at least one CYP2C19*2
      allele had higher baseline PRI after the initial LD (78.2 +/- 13.1 vs. 65.3 +/-
      19.5, P=0.005). The PRI reduction with additional LD was significantly smaller in
      carriers of the CYP2C19*2 (25.2 +/- 15.6 vs. 35.5 +/- 16.8, P=0.025) and similar
      trend was observed with subsequent additional LDs. Both MDs were less effective
      in presence of CYP2C19*2. Target PRI was, however, more frequently achieved with
      higher MD even in presence of CYP2C19*2 (in 70.6% vs. 23.5% of hyporesponders,
      P=0.008). No such differences were observed for other polymorphisms. CONCLUSIONS:
      In patients hyporesponsive to a routine clopidogrel doses the potency of
      additional LD and higher MD of clopidogrel is compromised by presence of
      CYP2C19*2 allele. The dose-adjustment strategy is not affected by ABCB1 C3435T or
      CYP2C9 genotypes.

PMID- 25060202
TI  - Cure rates of childhood acute lymphoblastic leukemia in Lithuania and the benefit
      of joining international treatment protocol.
AB  - BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) represents the largest
      group of pediatric malignancies with long-term survival rates of more than 80%
      achieved in developed countries. Epidemiological data and survival rates of
      childhood ALL in Lithuania were lacking. Therefore, the aim of this study was to
      analyze the population-based long-term treatment results of childhood ALL in
      Lithuania during 1992-2012. MATERIALS AND METHODS: Data of all 459 children with
      T-lineage and B-cell precursor ALL treated in Lithuania from 1992 to 2012 were
      collected and analyzed. Results were compared among four time-periods: 1992-1996
      (N=132), 1997-2002 (N=136), 2003-2008 (N=109) and 2009-2012 (N=82). RESULTS: The
      incidence of childhood ALL in Lithuania was 3.2-3.6 cases per 100000 children per
      year during the study period. Five-year probability of event-free survival
      increased from 50%+/- 4% in 1992-1996 to 71%+/- 4% in 2003-2008 (P<0.001). Five
      year cumulative incidence of relapses reduced from 27%+/- 4.5% in 1992-1996 to
      14%+/- 3.6% in 2003-2008 (P=0.042). After introduction of high-dose methotrexate
      of 5 g/m(2), cumulative incidence of CNS-involving relapses reduced from 17%+/-
      3.9% in 1992-1996 to 1%+/- 1.0% in 2003-2008 (P<0.001). Trend for further
      improvement in survival was seen in 2009-2012 when Lithuania joined international
      the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL-2008
      treatment protocol. CONCLUSIONS: Cure rates of childhood ALL in Lithuania are
      improving steadily and are now approaching those reported by the largest
      international study groups. The reasons for such a positive effect are both
      better financial support for treatment of children with cancer in Lithuania and
      international collaboration with joining international treatment protocol for
      childhood ALL.

PMID- 25060203
TI  - Cyclosporine therapeutic window evaluation by Chebyshev's inequality method in
      kidney recipients.
AB  - OBJECTIVE: The aim of this study was to identify a cyclosporine therapeutic range
      for kidney recipients. MATERIALS AND METHODS: The cyclosporine exposure level was
      based on the calculation of the mean area under the concentration-time curve
      AUC(0-12). The AUC(0-12) was estimated using a Bayesian estimator and a 3-point
      limited sampling strategy. Cyclosporine exposure levels were obtained from 3
      blood samples: 0, 1, and 3h postdose; and analyses were performed using a liquid
      chromatography-tandem mass spectrometry method. The therapeutic window of
      cyclosporine was calculated by the Chebyshev's inequality method with a 99%
      guarantee (alpha=0.01) using the IBM SPSS Statistics 20 software. RESULTS: It was
      found that the therapeutic window of cyclosporine estimated by the Chebyshev's
      inequality method and put on the AUC(0-12) exposure lies in the ranges from 2.84
      3.13 mg h/L with the 99% confidence for the patients with the target AUC(0-12)
      exposure of 3.8 mg h/L (posttransplantation time >1 year). The therapeutic window
      of cyclosporine differs in different posttransplantation time groups: the
      estimated AUC exposure range in the group of patients who have a graft longer
      than 5 years is 2.70-2.98 mg h/L, and the estimated AUC exposure range in the
      group of patients who have a graft for 1-5 years is 3.05-3.75 mg h/L.
      CONCLUSIONS: Chebyshev's inequality could be an appropriate and more precise
      method to determine the therapeutic window for cyclosporine in kidney recipients
      than the target AUC(0-12) value and further studies should be conducted to
      evaluate patients with postoperative time <1 year.

PMID- 25060204
TI  - Prevalence of dyslipidemia in statin-treated patients in the Baltic states
      (Estonia, Latvia, and Lithuania): results of the Dyslipidemia International Study
      (DYSIS).
AB  - BACKGROUND AND OBJECTIVE: The Baltic nations (Estonia, Latvia, and Lithuania) are
      profoundly affected by cardiovascular disease (CVD). Studies have indicated that
      patients may experience persistent dyslipidemia despite chronic statin treatment.
      Therefore, the aim of this study was to analyze the risk factors for dyslipidemia
      despite statin-treatment in a large dataset from the Baltic nations. MATERIAL AND
      METHODS: Patients in primary care centers across the Baltic nations were enrolled
      into the cross-sectional, observational Dyslipidemia International Study (DYSIS).
      Patients were >= 45 years old and had been treated with statins for at least
      three months. Patient characteristics and lipid measurements were used to
      determine variables contributing to dyslipidemia (abnormal low-density
      lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], or
      total triglyceride [TG] values). RESULTS: We enrolled 1797 patients with a mean
      age of 66.1 years and 59.1% being female. Overall 63.4% had cardiovascular
      disease, 30.1% were diabetic and 77.8% at high risk for cardiovascular
      complications. LDL-C was not at target level for 80.7%; low HDL-C levels were
      observed for 26.0%, and elevated TG levels were found in 35.0% of all patients.
      Multivariate analyses indicated that a BMI >= 30 kg/m(2) (OR, 2.12; 95% CI, 1.45
      3.08) and hypertension (OR, 2.43; 95% CI, 1.1 6-5.10) were strongly associated
      with dyslipidemia (involving all three lipids) during statin therapy while age >=
      70 years (OR, 0.63; 95% CI, 0.42-0.94) and female gender (OR, 0.48; 95% CI, 0.33
      0.68) conferred reduced risk. CONCLUSIONS: Our findings indicate many statin
      treated patients in Estonia, Latvia, and Lithuania did not meet target lipid
      levels and had a very high risk of CVD. Combating other well-known CVD risk
      factors such as obesity and hypertension is vital to reduce the exceptionally
      high risk for CVD mortality seen in the Baltic nations.

PMID- 25060205
TI  - Direct cost of patients with type 2 diabetes mellitus healthcare and its
      complications in Lithuania.
AB  - OBJECTIVE: The main objective of this study was to estimate the annual direct
      healthcare cost of type 2 diabetes mellitus healthcare and its complications in
      Lithuanian population. MATERIAL AND METHODS: The study uses a prevalence-based
      top-down approach. The random sample of study participants was formed using the
      database of the National Health Insurance Fund under the Lithuanian Ministry of
      Health. 762 patients with diabetes mellitus type 2 data were analyzed in this
      research. The data on healthcare costs was recorded between January 1, 2011 and
      December 31, 2011. RESULTS: Ambulatory care cost mean per patients with diabetes
      mellitus type 2 in 2011 was EUR 156.14 (95% CI, 147.05-165.24). 34.4% patients
      had at least one hospitalization during the 2011 year. Mean annual cost per
      patients of hospitalization was EUR 1160.16 (95% CI, 1019.60-1300.73). Covered
      drugs and diabetes supplies annual direct cost mean per patients was EUR 448.34
      (95% CI, 411.14-485.54). The more expensive treatment was with oral and non
      insulin injectable hypoglycemic medications (P<0.001). 65.1% participants were
      diagnosed one or more diabetes-related chronic complications. Average annual cost
      per person, increased gradually with the numbers of complications from EUR 671.94
      (95% CI, 575.03-768.86) in patients without complications to EUR 1588.98 (95% CI,
      1052.09-2125.86) in patients with 3 and more complications (P<0.001).
      CONCLUSIONS: The largest part of direct costs in diabetes mellitus healthcare
      composes hospital inpatient care and covered drugs expenditures. In our study we
      observed that the presence of microvascular, macrovascular chronic complication
      increased the direct cost per patient, compared with patients without
      complications.

PMID- 25060206
TI  - The relationship between abuse, psychosocial factors, and pain complaints among
      older persons in Europe.
AB  - BACKGROUND AND OBJECTIVE: Abuse and pain complaints are common among older
      persons. However, little is known about relationships between abuse (e.g.
      psychological) and pain complaints (e.g. backache) among older persons while
      considering other factors (e.g. depression). Therefore, the aim of this study was
      to determine these relationships. MATERIALS AND METHODS: The design was cross
      sectional. A total of 4467 women and men aged 60-84 years from Germany, Greece,
      Italy, Lithuania, Portugal, Spain, and Sweden answered questionnaires regarding
      various areas such as abuse, mental health (e.g. anxiety) and pain complaints
      (e.g. backache). The data were examined with bivariate (analyses of variance) and
      multivariate methods (linear regressions). RESULTS: The bivariate analyses showed
      that psychological abuse was connected with all pain complaints; physical with
      headache and head pressure; sexual with neck or shoulder pain and headache;
      injury with all complaints (except pain in joints or limbs); financial with pain
      in joints or limbs and head pressure; and overall abuse (one or more types) with
      all complaints (except headache). The regressions showed that psychological abuse
      increased the likelihood of being affected by head pressure and heaviness or
      tiredness in the legs; physical abuse of being affected by headache and head
      pressure; financial abuse of being affected by head pressure; and overall abuse
      of being affected by headache and head pressure. In general, respondents from
      Sweden and younger (60-64 years) were less affected by the complaints than those
      from other countries (e.g. Germany) and older (e.g. 70-74 years), respectively.
      Respondents on medication (e.g. pain killers) were less affected by all pain
      complaints and those with high social support by pain in joints or limbs. High
      scores on anxiety and depression and having many diseases increased the
      likelihood of being affect by all pain complaints. CONCLUSIONS: Abuse was related
      with certain pain complaints (e.g. headache), but other factors and in particular
      mental health and physical diseases impacted on all pain complaints. Medication
      and partly social support had a positive effect on the pain experience, i.e. the
      complaints interfered less with for instance the daily-life of the respondents.

PMID- 25060207
TI  - Positron emission tomographic imaging of copper 64- and gallium 68-labeled
      chelator conjugates of the somatostatin agonist tyr3-octreotate.
AB  - The bifunctional chelator and radiometal have been shown to have a direct effect
      on the pharmacokinetics of somatostatin receptor (SSTR)-targeted imaging agents.
      We evaluated three Y3-TATE analogues conjugated to NOTA-based chelators for
      radiolabeling with 64Cu and 68Ga for small-animal positron emission
      tomographic/computed tomographic (PET/CT) imaging. Two commercially available
      NOTA analogues, p-SCN-Bn-NOTA and NODAGA, were evaluated. The p-SCN-Bn-NOTA
      analogues were conjugated to Y3-TATE through beta-Ala and PEG8 linkages. The
      NODAGA chelator was directly conjugated to Y3-TATE. The analogues labeled with
      64Cu or 68Ga were analyzed in vitro for binding affinity and internalization and
      in vivo by PET/CT imaging, biodistribution, and Cerenkov imaging (68Ga
      analogues). We evaluated the effects of the radiometals, chelators, and linkers
      on the performance of the SSTR subtype 2--targeted imaging agents and also
      compared them to a previously reported agent, 64Cu-CB-TE2A-Y3-TATE. We found that
      the method of conjugation, particularly the length of the linkage between the
      chelator and the peptide, significantly impacted tumor and nontarget tissue
      uptake and clearance. Among the 64Cu- and 68Ga-labeled NOTA analogues, NODAGA-Y3
      TATE had the most optimal in vivo behavior and was comparable to 64Cu-CB-TE2A-Y3
      TATE. An advantage of NODAGA-Y3-TATE is that it allows labeling with 64Cu and
      68Ga, providing a versatile PET probe for imaging SSTr subtype 2-positive tumors.

PMID- 25060208
TI  - Pulmonary hypertension and Hashimoto's thyroiditis: does a relationship exist?
AB  - Several studies examined the possibility that idiopathic pulmonary hypertension
      is related to thyroid autoimmune diseases. The aim of our study was to highlight
      the possible correlations between the pulmonary hypertension and Hashimoto's
      thyroiditis (HT). A total of 93 patients were enrolled, 70 suffering from HT in
      euthyroidism state and 23 controls. All underwent anthropometric [weight (Kg);
      height (m); Body Mass Index (Kg/m(2)): waist circumference (cm)] and biochemical
      [fasting blood glucose (mg/dl), TSH (uUI/mL), FT3 (pg/ml), FT4 (pg/ml), total,
      HDL and LDL-cholesterol (mg/dl), triglycerides (mg/dl)] evaluations. All patients
      underwent two-dimensional trans-thoracic echocardiographic evaluations in order
      to measure systolic (sPAP) and the end-diastolic pressure of the pulmonary artery
      (dPAP). There were no differences between the two populations regarding
      anthropometric and biochemical parameters. Patients with HT had higher sPAP
      values than controls (Hashimoto: 20.06 +/- 6.56 mmHg vs controls: 19.96 +/- 8.58
      mmHg, p = 0.044). Patients with HT had lower dPAP values than controls (2.51 +/-
      0.90 mmHg vs. controls 3.17 +/- 1.58 mmHg, p < 0.0001), and there was a
      statistically significant difference in the left ventricle ejection fraction
      between the two groups (60.57 +/- 1.60 % in patients with HT vs. 61.04 +/- 2.03 %
      in controls, p = 0.037). The multivariate regression analysis did not confirm
      such results. We demonstrated that patients with HT did not show relevant
      pulmonary hypertension when compared to healthy controls.

PMID- 25060209
TI  - Diagnosis of de quervain's subacute thyroiditis via sensor-navigated 124Iodine
      PET/ultrasound (124I-PET/US) fusion.
AB  - The role of (124)Iodine-PET/US Fusion technique is demonstrated in a 52-year-old
      woman with De Quervain's subacute thyroiditis. A small and adversely located
      lesion not detected by thyroid scintigraphy could be unambiguously matched with a
      hypofunctional PET finding. The presented case supports the clinical potential of
      PET/US Fusion technique in thyroid disease especially in small and uncertain
      findings. 

PMID- 25060210
TI  - Resolving the effects of maternal and offspring genotype on dyadic outcomes in
      genome wide complex trait analysis ("M-GCTA").
AB  - Genome wide complex trait analysis (GCTA) is extended to include environmental
      effects of the maternal genotype on offspring phenotype ("maternal effects", M
      GCTA). The model includes parameters for the direct effects of the offspring
      genotype, maternal effects and the covariance between direct and maternal
      effects. Analysis of simulated data, conducted in OpenMx, confirmed that model
      parameters could be recovered by full information maximum likelihood (FIML) and
      evaluated the biases that arise in conventional GCTA when indirect genetic
      effects are ignored. Estimates derived from FIML in OpenMx showed very close
      agreement to those obtained by restricted maximum likelihood using the published
      algorithm for GCTA. The method was also applied to illustrative perinatal
      phenotypes from ~4,000 mother-offspring pairs from the Avon Longitudinal Study of
      Parents and Children. The relative merits of extended GCTA in contrast to
      quantitative genetic approaches based on analyzing the phenotypic covariance
      structure of kinships are considered. 

PMID- 25060211
TI  - Nordic pulse oximetry screening--implementation status and proposal for uniform
      guidelines.
AB  - AIM: Pulse oximetry screening of newborn infants increases early detection of
      critical congenital heart disease and minimises the risk of circulatory collapse
      before surgery. This study provides an update on the implementation of pulse
      oximetry screening in the Nordic countries and proposes standardised guidelines.
      METHODS: A questionnaire exploring pulse oximetry screening, clinical examination
      routines and availability of echocardiography was distributed to all 157 delivery
      units in the Nordic countries in June 2013. RESULTS: We received responses from
      156 of the 157 delivery units, and 116 (74%) were using pulse oximetry screening
      by September 2013. Preductal and postductal screening were both used in 59 of 116
      units (51%), with just postductal screening in 51 of 116 (44%) and just preductal
      screening alone in 6 of 116 (5%). Screening was performed before 24 h in 105 of
      116 units (91%). The implementation of screening was highest in Finland (29/30,
      97%), Sweden (42/46, 91%) and Norway (43/48, 90%) and lowest in Denmark (2/24,
      8%) and Iceland (0/8 units). CONCLUSION: In Sweden, Norway and Finland, the
      implementation of pulse oximetry screening is currently the highest in the world
      and coverage will be close to 100% in 2014. We propose uniform Nordic guidelines
      using preductal and postductal screening before 24 h of age.

PMID- 25060212
TI  - Biomechanical evaluation of bending strength of spinal pedicle screws, including
      cylindrical, conical, dual core and double dual core designs using numerical
      simulations and mechanical tests.
AB  - Pedicle screws are used for treating several types of spinal injuries. Although
      several commercial versions are presently available, they are mostly either fully
      cylindrical or fully conical. In this study, the bending strengths of seven types
      of commercial pedicle screws and a newly designed double dual core screw were
      evaluated by finite element analyses and biomechanical tests. All the screws had
      an outer diameter of 7 mm, and the biomechanical test consisted of a cantilever
      bending test in which a vertical point load was applied using a level arm of 45
      mm. The boundary and loading conditions of the biomechanical tests were applied
      to the model used for the finite element analyses. The results showed that only
      the conical screws with fixed outer diameter and the new double dual core screw
      could withstand 1,000,000 cycles of a 50-500 N cyclic load. The new screw,
      however, exhibited lower stiffness than the conical screw, indicating that it
      could afford patients more flexible movements. Moreover, the new screw produced a
      level of stability comparable to that of the conical screw, and it was also
      significantly stronger than the other screws. The finite element analysis further
      revealed that the point of maximum tensile stress in the screw model was
      comparable to the point at which fracture occurred during the fatigue test.

PMID- 25060213
TI  - Streptococcus bovis endocarditis as first clinical expression of an occult
      colorectal neoplasm.

PMID- 25060214
TI  - Comment on Koskenvuo et al.: Risk of cancer and secondary proctectomy after
      colectomy and ileorectal anastomosis in familial adenomatous polyposis.

PMID- 25060215
TI  - Left colon cancer presenting as fecopneumothorax: a case report and review of
      literature.

PMID- 25060216
TI  - Lymph node metastasis of carcinomas of transverse colon including flexures.
      Consideration of the extramesocolic lymph node stations.
AB  - PURPOSE: Complete mesocolic excision (CME) is nowadays state of the art in the
      treatment of colon cancer. In cases of carcinoma of transverse colon and of both
      flexures an extramesocolic lymph node metastasis can be found in the
      infrapancreatic lymph node region (ILR) and across the gastroepiploic arcade
      (GLR). These direct metastatic routes were not previously systematically
      considered. In order to validate our hypothesis of these direct metastatic
      pathways and to obtain evidence of our approach of including dissection of these
      areas as part of CME, we initiated a prospective study evaluating these lymph
      node regions during surgery. METHODS: Forty-five consecutive patients with
      primary tumour manifestation in transverse colon and both flexures between May
      2010 and January 2013 were prospectively analyzed. Patients were followed up for
      at least 6 months. Mode of surgery, histopathology, morbidity and mortality were
      evaluated. RESULTS: Twenty-six patients had a carcinoma of transverse colon, 16
      patients one of hepatic flexure and four patients one of splenic flexure. The
      median lymph node yield was 40. Occurrence of lymph node metastasis in ILR was
      registered in five patients and in GLR in four patients. The mean lymph node
      ratio was 0.085. Postoperative complications occurred in nine patients, and
      postoperative mortality was 2 %. CONCLUSIONS: We were able to demonstrate this
      novel metastatic route of carcinomas of the transverse colon and of both flexures
      in ILR and GLR. These could be considered as regional lymph node regions and have
      to be included into surgery for cancer of the transverse colon including both
      flexures.

PMID- 25060217
TI  - The urogenital-hypogastric sheath: an anatomical observation on the relationship
      between the inferomedial extension of renal fascia and the hypogastric nerves.
AB  - PURPOSE: The study aimed to perform an anatomical observation on the inferomedial
      extension of the renal fascia (RF) to the pelvis and explore its relationship
      with the hypogastric nerves (HGNs). METHODS: Gross anatomy was performed on 12
      formalin-fixed and 12 fresh cadavers. Sectional anatomy was performed on four
      formalin-fixed cadavers. RESULTS: Different from the traditional concept, both
      the anterior and posterior RF included the outer and inner layer with different
      inferomedial extensions. The multiple layers of RF extended downward to form a
      sandwich-like and compound fascia sheath with potential and expandable spaces
      which was named as "the urogenital-hypogastric sheath." Below the level of the
      origin of the inferior mesenteric artery, the bilateral urogenital-hypogastric
      sheath communicated with the counterpart in front of the great vessels in the
      midline and the superior hypogastric plexus ran into the urogenital-hypogastric
      sheath which carried the HGNs, ureters, and genital vessels downward to their
      terminations in the pelvis. In the retrorectal space, the urogenital-hypogastric
      sheath surrounded the fascia propria of the rectum posterolaterally as a layer of
      coat containing HGNs. CONCLUSION: The multiple layers of RF with different
      extensions are the anatomical basis of the formation of the urogenital
      hypogastric sheath. As a special fascial structure in the retroperitoneal space
      and the pelvis, emphasis on its formation and morphology may be helpful for not
      only unifying the controversies about the relationship between the pelvic fascia
      and HGNs but also improving the intraoperative preservation of the HGNs by
      dissecting in the correct surgical plane.

PMID- 25060218
TI  - The impact of pyrvinium pamoate on colon cancer cell viability.
AB  - PURPOSE: The in vitro and in vivo effects of pyrvinium pamoate (PP), a newly
      identified WNT signaling inhibitor, were evaluated against colon cancer cell
      lines and primary colon cancer samples. EXPERIMENTAL DESIGN: Antiproliferative
      activity of PP and its effects on protein and RNA levels of WNT targets were
      evaluated on adenomatous polyposis coli (APC (mut)) and beta-catenin(mut) cell
      lines, one WNT(wt) colon cancer cell line, as well as six primary colon cancer
      samples with mutant APC in vitro. In addition, the effect of PP on the growth of
      liver metastasis was examined. RESULTS: PP blocked colon cancer cell growth in
      vitro in a dose-dependent manner with great differences in the inhibitory
      concentration (IC(50)), ranging from 0.6 * 10(-6) to 65 * 10(-6) mol/L for colon
      cancer cells with mutations in WNT signaling. In addition, PP demonstrated a
      cytotoxic effect on primary colon cancer samples. A combined cytotoxic effect of
      PP with 5-fluorouracil (5-FU) was observed for two cell lines. PP decreased
      messenger RNA (mRNA) and protein levels of known WNT target genes as c-MYC and
      thereby led to the induction of p21. PP inhibited the migration of HCT116 colon
      cancer cells in vitro and decreased tumor growth in vivo after intraportal
      injection of HCT116 cells in nude mice. CONCLUSIONS: PP displays promising
      anticancer activity against a broad panel of human colon cancer cell lines, as
      well as primary colon cancer samples. However, our findings do not demonstrate a
      predominant cytotoxic effect of PP on colon cancer cells with mutations in WNT
      signaling.

PMID- 25060219
TI  - Can C-reactive protein predict the severity of a post-operative complication
      after elective resection of colorectal cancer?
AB  - AIMS: To explore if post-operative day 3 C-reactive protein (CRP), the ratio of
      pre-operative to day 3 white cell count (WCC) and platelet count can be used to
      predict the risk of post-operative complication and stratify the severity of
      complications as defined by the Clavien-Dindo classification. METHODS: Data was
      obtained retrospectively on 127 patients who had elective bowel resection for
      malignancy between 2011 and 2013. Baseline demographics and clinical details were
      obtained including pre-operative and day 3 WCC and platelets and day 3 CRP. Ratio
      of pre-operative to day 3 WCC and platelets was calculated. Outcome measures were
      if a complication occurred (death included) and complication as defined by the
      Clavien-Dindo clasification. Mann-Whitney U test and Kruskal-Wallis were used to
      test for significance. RESULTS: Of 127 patients, 57 % (n = 73) were male with a
      total median age of 72 and the commonest histology result T3N0 (40.6 %, n = 52).
      CRP was found to predict a complication (p < 0.0005) and the severity of
      complication as per the Clavien-Dindo classification (p < 0.0005). Day 3 CRP over
      285 suggested a life-threatening complication (Clavien-Dindo score 4). There was
      no statistical significance between the ratio of WCC and platelets to any of the
      outcome measures. CONCLUSIONS: WCC, platelets and CRP are routinely performed in
      the post-operative period. Previous research has shown CRP to be a good predictor
      of a complication. This paper has shown that day 3 CRP can not only predict but
      can also stratify the severity of post-operative complications.

PMID- 25060220
TI  - Laparoscopic appendectomy for chronic right lower quadrant abdominal pain.
AB  - PURPOSE: The appendix can be a rare cause for chronic right lower quadrant
      abdominal pain (RLQAP), even though no objective disorder can be determined to
      the appendix. This condition can be described as chronic appendicitis or
      (neurogenic) appendicopathy. After careful selection, elective appendectomy is
      performed in our centre for this group of patients. METHODS: All patients that
      underwent an elective appendectomy between 2006 and 2013 were prospectively
      analysed. Inclusion criterion was chronic RLQAP without abnormalities seen on
      imaging. Exclusion criterion was pain after conservative treatment of
      (complicated) appendicitis or an abnormal appendix on imaging like a mass,
      mucocoele or faecolith. Primary outcome was the effect on the pain
      postoperatively. RESULTS: In the period of the study, ten patients met the
      inclusion criteria and underwent an appendectomy for chronic RLQAP. Average
      preoperative pain score assessed with visual analogue scale (VAS) was 8.6.
      Preoperative work-up showed no abnormalities. No macroscopic abnormalities were
      seen during surgery in any of the patients. Histopathological analysis was
      obtained and showed limited abnormalities in eight of ten patients, mostly
      suspicion of previous inflammation. Postoperatively, no complications occurred,
      and at revision after 3 weeks, average VAS was 1.0. Long-term follow-up showed
      that patients remained free of symptoms; average VAS after a median of 33 months
      was 1.0. CONCLUSIONS: A significant reduction of pain was achieved after an
      appendectomy in all patients suffering from chronic RLQAP in this series. Seven
      out of ten patients were completely free of pain.

PMID- 25060221
TI  - Early prediction of response by 18F-FDG PET/CT during preoperative therapy in
      locally advanced rectal cancer: a systematic review.
AB  - AIM: To assess the predictive value of fluorine-18-fluorodeoxyglucose ((18)F-FDG)
      positron emission tomography/computed tomography (PET/CT) in early assessing
      response during neo-adjuvant chemoradiotherapy (CRT) in patients with locally
      advanced rectal cancer. MATERIALS AND METHODS: A systematic review was performed
      by search of MEDLINE Library for the following terms: "rectal carcinoma OR rectal
      cancer", "predictive OR prediction OR response assessment OR response OR
      assessment", "early OR ad interim", "therapy", "FDG OR (18)F-FDG", "PET OR
      PET/CT". Articles performed by the use of stand-alone PET scanners were excluded.
      RESULTS: 10 studies met the inclusion criteria, including 302 patients. PET/CT
      demonstrated a good early predictive value in the global cohort (mean sensitivity
      = 79%; mean specificity = 78%). SUV and its percentage decrease (response index =
      RI) were calculated in all studies. A higher accuracy was demonstrated for RI
      (mean sensitivity = 82%; pooled specificity = 85%) with a mean cut-off of 42%.
      The mean time point to perform PET scan during CRT resulted to be at 1.85 weeks.
      Some PET parameters resulted to be both predictive and not statistical predictive
      of response, maybe due to the small population and few studies bias. CONCLUSION:
      PET showed high accuracy in early prediction response during preoperative CRT,
      increased with the use of RI as parameter. In the era of tailored treatment, the
      precocious assessment of non-responder patients allows modification of the
      subsequent strategy especially the timing and the type of surgical approach.

PMID- 25060223
TI  - Vascular imaging before intravenous thrombolysis: consequences of in-hospital
      delay in applying two diagnostic procedures.
AB  - BACKGROUND: Vascular imaging is increasingly used for diagnosis of arterial
      occlusions in acute ischemic stroke (AIS) patients. Our aim was to determine
      whether computed tomography angiography (CTA) and Doppler/duplex ultrasound (DUS)
      before intravenous thrombolysis (IVT) is associated with a delay in time-to
      treatment. METHODS: Observational analysis of a prospective cohort of AIS
      patients treated with IVT from January 2009 to December 2012. Patients were
      classified into three groups: the noncontrast computed tomography (NCCT) group
      (patients studied only with NCCT before IVT), CTA group (patients who underwent
      CTA in addition to NCCT), and the DUS group (patients studied with NCCT+DUS).
      RESULTS: We treated 244 patients: 116 patients (47.5%) were studied with NCCT, 79
      (32.4%) with CTA, and 49 (20.1%) with DUS. Door-to-needle time was significantly
      higher in the CTA group (median 60 [48-77] minutes) than in the NCCT group (51.5
      [40-65]) and DUS group (48 [42-61]) (P = .008). No differences were observed for
      onset-to-door time and onset-to-needle time. In the multivariate linear
      regression analysis, onset-to-door time, prehospital stroke code activation, and
      performance of CTA influenced door-to-needle time. CONCLUSIONS: Performing CTA
      before IVT seems to increase door-to-needle time. Vascular imaging based on DUS
      should be considered only if this does not lead to in-hospital delay.

PMID- 25060224
TI  - Factors influencing linezolid-nonsusceptible coagulase-negative staphylococci
      dissemination among patients in the intensive care unit: a retrospective cohort
      study.
AB  - BACKGROUND: The aim of the present study was to identify risk factors for
      linezolid-nonsusceptible coagulase-negative staphylococci (CNS) dissemination in
      the intensive care unit. METHODS: Among the 246 patients included, 33 revealed a
      linezolid-nonsusceptible CNS-positive culture specimen, 68 were positive for
      linezolid-susceptible CNS and 145 served as controls. Isolates were characterized
      by phenotypic and genotypic methods to species level, susceptibility to
      antistaphylococcal agents and clones. RESULTS: Among the 33 linezolid
      nonsusceptible CNS patients, 29 revealed Staphylococcus epidermidis and 4
      Staphylococcus capitis. All S. epidermidis strains belonged to the ST22 clone (by
      multilocus sequence typing), 26 carried both C2534T and T2504A and 3 strains were
      C2543T mutations. S. capitis strains were stratified as a common pulsed-field gel
      electrophoresis type and carried the G2576T mutation. Risk factors for linezolid
      nonsusceptible CNS isolation were linezolid administration and mean number of
      linezolid-nonsusceptible CNS-positive patients in nearby beds per day.
      CONCLUSIONS: These results reinforce the aspect of rational antibiotic usage, but
      also highlight the need for strict infection control measures to prevent the
      dissemination of linezolid-nonsusceptible CNS.

PMID- 25060222
TI  - TLR7-expressing cells comprise an interfollicular epidermal stem cell population
      in murine epidermis.
AB  - Normal interfollicular epidermis (IFE) homeostasis is maintained throughout the
      entire life by its own stem cells that self-renew and generate progeny that
      undergo terminal differentiation. However, the fine markers of the stem cells in
      interfollicular epidermis are not well defined yet. Here we found that TLR7
      identified the existence of progenitors and interfollicular epidermal stem cells
      in murine skin. In vitro, TLR7-expressing cells comprised of two subpopulations
      that were competent to proliferate and exhibited distinct differentiation
      potentials. Three-dimensional (3D) organotypic culture and skin reconstitution
      assays showed that TLR7-expressing cells were able to reconstruct the
      interfollicular epidermis. Finally, TLR7-expressing cells maintained the intact
      interfollicular epidermal structures revealed in serial transplantation assays in
      vivo in mice. Taken together, our results suggest that TLR7-expressing cells
      comprise an interfollicular epidermal stem cell population. 

PMID- 25060225
TI  - Phenotypic and genotypic characterisation of Haemonchus spp. and other
      gastrointestinal nematodes resistant to benzimidazole in infected calves from the
      tropical regions of Campeche State, Mexico.
AB  - The aim of this study was to identify the presence of anthelmintic resistance to
      benzimidazole (BZ) in gastrointestinal nematodes (GIN) from naturally infected
      calves in the tropical regions of Campeche State of Mexico. The faecal egg count
      reduction test (FECRT) was conducted at 10 livestock farms localised in the
      Carmen, Candelaria, Champoton, Escarcega and Palizada municipalities of Campeche.
      The assessed anthelmintic was albendazole. The trial period was between August
      and November 2012. Infected calves were allocated into two groups, control and
      treated, on each farm. The number of eggs excreted per g of faeces was estimated
      by the McMaster technique at 0 and 14 days pre- and post- treatment,
      respectively. Recovered infective larvae (L3) (pre- and post-treatment) were
      identified using taxonomic keys and a genomic DNA (gDNA) template from a pool of
      L3 species prior to BZ treatment. Additionally, BZ-resistance polymorphisms in
      Haemonchus were determined by Allele Specific PCR (AS-PCR) at codon 200 and by
      end-point PCR at codons 200, 198 and 167 from isotype 1 of the beta-tubulin gene.
      Morphological identification revealed Haemonchus, Cooperia, Trichostrongylus,
      Ostertagia and Oesophagostumum L3 species before BZ treatment, and Haemonchus and
      Cooperia L3 species after treatment. Additionally, of the GIN populations, three
      exhibited BZ resistance, and seven were BZ-susceptible by FECRT. Molecular
      analysis identified mutations in Haemonchus populations on nine farms at codon
      200 (TTC to TAC) by AS-PCR, while no changes were observed at 167 (TTC to TAC) or
      198 (GAA to GCA) codons in any population. In conclusion, resistance to BZ was
      determined in Haemonchus and Cooperia nematodes in infected cattle in five
      tropical regions of Campeche State. 

PMID- 25060226
TI  - Genetically distinct isolates of Spirocerca sp. from a naturally infected red fox
      (Vulpes vulpes) from Denmark.
AB  - Spirocerca lupi causes formation of nodules that may transform into sarcoma in
      the walls of aorta, esophagus and stomach of infected canids. In February 2013,
      post mortem examination of a red fox (Vulpes vulpes) hunted in Denmark revealed
      the presence of several nodules containing adult worms of Spirocerca sp. in the
      stomach and the omentum. The nodules largely consisted of fibrous tissue with
      infiltration of mononuclear cells, neutrophilic granulocytes and macrophages with
      hemosiderin deposition. Parasitological examination by three copromicroscopic
      methods, sedimentation, flotation with saturated sugar-salt solution, and sieving
      failed to detect eggs of Spirocerca sp. in feces collected from the colon. This
      is the first report of spirocercosis in Denmark, and may have been caused by a
      recent introduction by migrating paratenic or definitive host. Analysis of two
      overlapping partial sequences of the cox1 gene, from individual worms, revealed
      distinct genetic variation (7-9%) between the Danish worms and isolates of S.
      lupi from Europe, Asia and Africa. This was confirmed by phylogenetic analysis
      that clearly separated the Danish worms from other isolates of S. lupi. The
      distinct genetic differences of the current worms compared to other isolates of
      S. lupi may suggest the presence of a cryptic species within Spirocerca. 

PMID- 25060227
TI  - Molecular and ultrastructural characterization of Haplosporidium diporeiae n.
      sp., a parasite of Diporeia sp. (Amphipoda, Gammaridea) in the Laurentian Great
      Lakes (USA).
AB  - BACKGROUND: The phylum Haplosporidia contains coelozoic and histozoic, spore
      forming, obligate protozoan endoparasites that infect a number of freshwater and
      marine invertebrates including bivalves, crustaceans, and polychaetes. In
      amphipods, haplosporidians cause systemic infection resulting in a range of
      pathologies. While amphipods belonging to the genus Diporeia (Gammarideae) have
      been shown to host haplosporidians, the taxonomic relationship of the Diporeia
      haplosporidian(s) is largely unknown due to the lack of phylogenetic and detailed
      ultrastructural studies. METHODS: The infection characteristics and taxonomic
      identity of a haplosporidian infecting Diporeia spp. (Diporeia) were based on
      microscopical investigation, electron microscopy, and Bayesian phylogenetic
      inference using haplosporidian 16S rRNA gene sequences. RESULTS: In stained
      sections, the haplosporidian was observed to cause systemic infections in
      Diporeia that were often accompanied with host tissue degeneration. The
      haplosporidian appeared as binucleate plasmodia and sporocysts containing
      different spore maturation stages in the coelom, connective tissue, digestive
      tissue, and muscle. All of the observed systemic infections progressed to
      sporogenesis. Transmission electron microscopy revealed that fixed mature spores
      were slightly ellipsoidal and had a mean spore length X width of 5.34 +/- 0.17 *
      4.09 +/- 0.15 MUm. A hinged opercular lid with a length of 3.1 +/- 0.17 MUm was
      observed for a number of developing spores. The average thickness of the cell
      wall was 90.0 +/- 8.33 nm. Thin filaments (70 nm) composed of spore wall material
      were observed projecting from an abopercular thickening of the spore wall.
      Phylogenetic analysis showed that the haplosporidian is novel bearing some
      similarities with the oyster pathogen Haplosporidium nelsoni, yet distinctly
      different. CONCLUSIONS: Based on its morphology, genetic sequence, and host, it
      became evident that the Diporeia haplosporidian is taxonomically novel and we
      propose its nomenclature as Haplosporidium diporeiae. This is the first report of
      a haplosporidian infecting Diporeia in Lake Superior.

PMID- 25060228
TI  - Regioselective deiodination of iodothyronamines, endogenous thyroid hormone
      derivatives, by deiodinase mimics.
AB  - Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that play an
      important role in the activation and inactivationL of thyroid hormones. It is
      known that iodothyronamines (TnAMs), produced by the decarboxylation of thyroid
      hormones, act as substrates for deiodinases. To understand whether
      decarboxylation alters the rate and/or regioselectivity of deiodination by using
      synthetic deiodinase mimics, we studied the deiodination of different
      iodothyronamines. The triiodo derivative 3,3',5-triiodothyronamine (T3 AM) is
      deiodinated at the inner ring by naphthyl-based deiodinase mimics, which is
      similar to the deiodination of 3,3',5-triiodothyronine (T3). However, T3 AM
      undergoes much slower deiodination than T3. Detailed experimental and theoretical
      investigations suggest that T3 AM forms a weaker halogen bond with selenium
      donors than T3. Kinetic studies and single-crystal X-ray structures of T3 and T3
      AM reveal that intermolecular I???I interactions may play an important role in
      deiodination. The formation of hydrogen- and halogen-bonding assemblies, which
      leads to the formation of a dimeric species of T3 in solution, facilitates the
      interactions between the selenium and iodine atoms. In contrast, T3 AM, which
      does not have I???I interactions, undergoes much slower deiodination. 

PMID- 25060229
TI  - Vulvar and pelvic pain terminology review: implications for microsurgeons.

PMID- 25060230
TI  - Regulatory functions of B cells in allergic diseases.
AB  - B cells are essentially described for their capacity to produce antibodies
      ensuring anti-infectious immunity or deleterious responses in the case of
      autoimmunity or allergy. However, abundant data described their ability to
      restrain inflammation by diverse mechanisms. In allergy, some regulatory B-cell
      subsets producing IL-10 have been recently described as potent suppressive cells
      able to restrain inflammatory responses both in vitro and in vivo by regulatory T
      cell differentiation or directly inhibiting T-cell-mediated inflammation. A
      specific deficit in regulatory B cells participates to more severe allergic
      inflammation. Induction of allergen tolerance through specific immunotherapy
      induces a specific expansion of these cells supporting their role in
      establishment of allergen tolerance. However, the regulatory functions carried
      out by B cells are not exclusively IL-10 dependent. Indeed, other regulatory
      mechanisms mediated by B cells are (i) the production of TGF-beta, (ii) the
      promotion of T-cell apoptosis by Fas-Fas ligand or granzyme-B pathways, and (iii)
      their capacity to produce inhibitory IgG4 and sialylated IgG able to mediate anti
      inflammatory mechanisms. This points to Bregs as interesting targets for the
      development of new therapies to induce allergen tolerance. In this review, we
      highlight advances in the study of regulatory mechanisms mediated by B cells and
      outline what is known about their phenotype as well as their suppressive role in
      allergy from studies in both mice and humans. 

PMID- 25060231
TI  - Knowledge, attitudes, and practices for cervical cancer screening among the
      Bhutanese refugee community in Omaha, Nebraska.
AB  - Cervical cancer is the second most common cause of cancer mortality among women
      with the vast majority of patients in developing countries. Bhutanese refugees in
      the United States are from South Central Asia, the 4th leading region of the
      world for cervical cancer incidence. Over the past few years, Bhutanese refugees
      have increased significantly in Nebraska. This study evaluates current knowledge
      of cervical cancer and screening practices among the Bhutanese refugee women in
      Omaha, Nebraska. The study aimed to investigate cervical cancer and screening
      knowledge and perceptions about the susceptibility and severity of cervical
      cancer and perceived benefits and barriers to screening. Self-administered
      questionnaires and focus groups based on the Health Belief Model were conducted
      among 42 healthy women from the Bhutanese refugee community in Omaha. The study
      revealed a significant lack of knowledge in this community regarding cervical
      cancer and screening practices, with only 22.2 % reporting ever hearing of a Pap
      test and 13.9 % reporting ever having one. Only 33.3 % of women were in agreement
      with their own perceived susceptibility to cervical cancer. Women who reported
      ever hearing about the Pap test tended to believe more strongly about curability
      of the disease if discovered early than women who never heard about the test
      (71.4 vs. 45.0 %, for the two groups. respectively). Refugee populations in the
      United States are in need for tailored cancer education programs especially when
      being resettled from countries with high risk for cancer.

PMID- 25060232
TI  - The impact of state certification of community health workers on team climate
      among registered nurses in the United States.
AB  - A number of states have adopted certification programs for community health
      workers (CHWs) to improve recognition of CHWs as members of health care teams,
      increase oversight, and to provide sustainable funding. There has been little
      research into the impact of state CHW certification on the diffusion and adoption
      of CHWs into existing health care systems. This study examined the impact of
      state CHW certification on the perceptions of team climate among registered
      nurses (RNs) who work with CHWs in states with and without CHW certification
      programs. The study recruited RNs using a purposeful sampling method and used an
      online survey, which included the Team Climate Inventory (TCI), and compared the
      perceptions of team climate between the two groups. The study found no
      significant differences in the overall mean TCI score or TCI subscale scores
      between RNs who work in states with CHW certification programs (n = 81) and those
      who work in states without CHW certification programs (n = 115). There was a
      statistically significant difference on one survey question regarding whether RNs
      believe state certification of CHWs improved the ability of their health care
      team to deliver quality care. More research is needed to assess impact of state
      certification of CHWs and other factors that influence the diffusion and adoption
      of CHWs into the current health care system.

PMID- 25060233
TI  - Charge-tunable polymers as reversible and recyclable flocculants for the
      dewatering of microalgae.
AB  - Microalgae-derived biofuels have potential advantages over other renewable, crop
      based resources; however, large-scale production is not currently economical due,
      in part, to challenges in the harvesting step. In this article, we present a
      novel approach for the dewatering and harvesting of microalgae using flocculants
      that can be recovered and recycled. Polyampholytes with molecular charges
      dependent upon pH (ranging from net positively- to net negatively-charged) are
      used as a model flocculant system and provide reversible electrostatic
      interactions with the negatively-charged algal cells. These pH-dependent
      properties allow the polyampholytic flocculants to efficiently desorb from
      concentrated biomass and, unlike most commercial flocculants that have
      permanently charged functionalities, be recovered and recycled for further
      dewatering processes. The behavior of the model polyampholytic flocculants is
      characterized for the dewatering of Chlorella vulgaris (UTEX 395). The reversible
      and recyclable flocculants achieve >99% flocculation efficiencies, are recovered
      at more than 98 wt% yields after biomass dewatering, and can be recycled over
      five times for flocculation.

PMID- 25060234
TI  - Cysteine-2 and Cys30 are essential for chlorophyll-binding activity of the water
      soluble chlorophyll-binding protein (WSCP) of Chenopodium album.
AB  - Chenopodium album has a non-photosynthetic chlorophyll protein known as the water
      soluble chlorophyll (Chl)-binding protein (WSCP). The C. album WSCP (CaWSCP) is
      able to photoconvert the chlorin skeleton of Chl a into a bacteriochlorin-like
      skeleton. Reducing reagents such as beta-mercaptoethanol or dithiothreitol
      inhibit photoconversion, indicating that S-S bridge(s) in CaWSCP are quite
      important for it. Recently, we found that the mature region of CaWSCP contains
      five cysteine residues; Cys2, Cys30, Cys48, Cys63, and Cys144. To identify which
      cysteine residues are involved in the photoconversion, we generated five mutants
      (C2S, C30S, C48S, C63S, and C144S) by site-directed mutagenesis. Interestingly,
      C48S, C63S, and C144S mutants showed the same Chl-binding activity and
      photoconvertibility as those of the recombinant wild-type CaWSCP-His, while the
      C2S and C30S mutants completely lost Chl-binding activity. Our findings indicated
      that the S-S bridge between Cys2 and Cys30 in each CaWSCP subunit is essential
      for Chl-binding activity.

PMID- 25060235
TI  - Contextualized analysis of a needs assessment using the Theoretical Domains
      Framework: a case example in endocrinology.
AB  - BACKGROUND: The Theoretical Domains Framework (TDF) is a set of 14 domains of
      behavior change that provide a framework for the critical issues and factors
      influencing optimal knowledge translation. Considering that a previous study has
      identified optimal knowledge translation techniques for each TDF domain, it was
      hypothesized that the TDF could be used to contextualize and interpret findings
      from a behavioral and educational needs assessment. To illustrate this
      hypothesis, findings and recommendations drawn from a 2012 national behavioral
      and educational needs assessment conducted with healthcare providers who treat
      and manage Growth and Growth Hormone Disorders, will be discussed using the TDF.
      METHODS: This needs assessment utilized a mixed-methods research approach that
      included a combination of: [a] data sources (Endocrinologists (n:120), Pediatric
      Endocrinologists (n:53), Pediatricians (n:52)), [b] data collection methods
      (focus groups, interviews, online survey), [c] analysis methodologies
      (qualitative - analyzed through thematic analysis, quantitative - analyzed using
      frequencies, cross-tabulations, and gap analysis). Triangulation was used to
      generate trustworthy findings on the clinical practice gaps of endocrinologists,
      pediatric endocrinologists, and general pediatricians in their provision of care
      to adult patients with adult growth hormone deficiency or acromegaly, or
      children/teenagers with pediatric growth disorders. The identified gaps were then
      broken into key underlying determinants, categorized according to the TDF
      domains, and linked to optimal behavioral change techniques. RESULTS: The needs
      assessment identified 13 gaps, each with one or more underlying determinant(s).
      Overall, these determinants were mapped to 9 of the 14 TDF domains. The Beliefs
      about Consequences domain was identified as a contributing determinant to 7 of
      the 13 challenges. Five of the gaps could be related to the Skills domain, while
      three were linked to the Knowledge domain. CONCLUSIONS: The TDF categorization of
      the needs assessment findings allowed recommendation of appropriate behavior
      change techniques for each underlying determinant, and facilitated communication
      and understanding of the identified issues to a broader audience. This approach
      provides a means for health education researchers to categorize gaps and
      challenges identified through educational needs assessments, and facilitates the
      application of these findings by educators and knowledge translators, by linking
      the gaps to recommended behavioral change techniques.

PMID- 25060236
TI  - The use of tooth crown measurements in the assessment of ancestry.
AB  - As the hardest tissue in the body, teeth have the potential to offer a wealth of
      biological information to the forensic anthropologist, which can include the
      assessment of ancestry. Using a large data set of dental measurements, the
      efficacy of mesiodistal and buccolingual tooth dimensions to discriminate between
      broad, geographically based groups is explored. A general pattern is identified:
      African populations have the largest teeth, Asians possess teeth of intermediate
      size, and Europeans have the smallest teeth. In a discriminant function analysis
      using crown measurements of all teeth (mandibular and maxillary and excluding the
      third molar), individuals were correctly classified in 71.3% of cases. When the
      sex of the individual is known, classification is improved up to 88.1% in females
      and 71.9% of males (cross-validated). Based on these results, we argue that
      dental metrics can be regularly employed as part of the development of the
      biological profile. 

PMID- 25060237
TI  - Multi-protein assemblies underlie the mesoscale organization of the plasma
      membrane.
AB  - Most proteins have uneven distributions in the plasma membrane. Broadly speaking,
      this may be caused by mechanisms specific to each protein, or may be a
      consequence of a general pattern that affects the distribution of all membrane
      proteins. The latter hypothesis has been difficult to test in the past. Here, we
      introduce several approaches based on click chemistry, through which we study the
      distribution of membrane proteins in living cells, as well as in membrane sheets.
      We found that the plasma membrane proteins form multi-protein assemblies that are
      long lived (minutes), and in which protein diffusion is restricted. The formation
      of the assemblies is dependent on cholesterol. They are separated and anchored by
      the actin cytoskeleton. Specific proteins are preferentially located in different
      regions of the assemblies, from their cores to their edges. We conclude that the
      assemblies constitute a basic mesoscale feature of the membrane, which affects
      the patterning of most membrane proteins, and possibly also their activity. 

PMID- 25060238
TI  - "Acute intrathoracic stomach!" How should we deal with complicated type IV
      paraesophageal hernias?
AB  - PURPOSE: Management of emergently admitted patients due to a complicated large
      paraesophageal hernia with acute symptoms of an "intrathoracic stomach" is
      controversial. The aim of this study was to clarify whether emergency surgery in
      such cases should be the procedure of choice. METHODS: The retrospective analysis
      of patients who were hospitalized due to emerging acute symptoms of an
      "intrathoracic stomach" between January 2009 and May 2013 was used as method.
      Patients were categorized into three groups: emergency operation within 24 h
      after admission, semi-elective operation within the first 7 days after admission
      and elective operation. RESULTS: Twenty-four patients were identified. Only three
      (12.5 %) patients required laparoscopic emergency surgery and two incurred a
      perioperative complication. In consequence of persistent or early recurrent
      complaints a laparoscopic operation was required prior to discharge semi-elective
      in 6/24 (25 %) patients without complications. The remaining 15/24 (62.5 %)
      patients were free of complaints after conservative therapy, but all of them
      decided upon elective operation after informed consent. One minor complication
      occurred. CONCLUSION: The majority of patients with acute symptoms due to an
      intrathoracic stomach can primarily be treated conservatively and timing of
      elective repair should be performed after resuscitation in a center of
      laparoscopic antireflux surgery.

PMID- 25060239
TI  - DNA methyltransferase immunohistochemical expression in odontogenic tumours.
AB  - BACKGROUND: Odontogenic tumours are a heterogeneous group of lesions formed from
      tissues that give rise to the tooth. DNA methylation, a covalent addition of a
      methyl group to the 5-carbon position of a cytosine nucleotide, is considered an
      important regulator of gene expression. The addition of the methyl radical is
      catalysed by DNA methyltransferases (DNMTs). Although some epigenetic studies
      have been conducted in odontogenic tumours, a study with the three types of DNMTs
      in several different members of this group is missing. This study analyses the
      expression of DNMTs in odontogenic tumours. METHODS: Formalin-fixed and paraffin
      embedded tissue samples of 20 ameloblastomas, 10 calcifying cystic odontogenic
      tumours, 10 calcifying epithelial tumours, 10 adenomatoid odontogenic tumours, 10
      keratocystic odontogenic tumours, five ameloblastic fibromas, two ameloblastic
      fibro-odontomas, four central odontogenic fibromas, seven peripheral odontogenic
      fibromas and 10 odontogenic myxomas were included. Immunohistochemical expression
      of DNMT1, 3A and 3B was assessed using a semi-quantitative analysis, and also a
      correlation with p21, p27 and E-cadherin immunoexpression was made. RESULTS:
      DNMT1, 3A and 3B were expressed in the nucleus and/or cytoplasm of all
      odontogenic tumours. DNMT1 expression was directly correlated with p27 expression
      in ameloblastomas. CONCLUSION: The high expression of DNMTs in odontogenic tumour
      cells suggests methylation as an important mechanism for this group of tumours.

PMID- 25060240
TI  - An evaluation of sharp cut cyclones for sampling diesel particulate matter
      aerosol in the presence of respirable dust.
AB  - Two prototype cyclones were the subjects of a comparative research campaign with
      a diesel particulate matter sampler (DPMS) that consists of a respirable cyclone
      combined with a downstream impactor. The DPMS is currently used in mining
      environments to separate dust from the diesel particulate matter and to avoid
      interferences in the analysis of integrated samples and direct-reading monitoring
      in occupational environments. The sampling characteristics of all three devices
      were compared using ammonium fluorescein, diesel, and coal dust aerosols. With
      solid spherical test aerosols at low particle loadings, the aerodynamic size
      selection characteristics of all three devices were found to be similar, with 50%
      penetration efficiencies (d 50) close to the design value of 0.8 MUm, as required
      by the US Mine Safety and Health Administration for monitoring occupational
      exposure to diesel particulate matter in US mining operations. The prototype
      cyclones were shown to have 'sharp cut' size-selection characteristics that
      equaled or exceeded the sharpness of the DPMS. The penetration of diesel aerosols
      was optimal for all three samplers, while the results of the tests with coal dust
      induced the exclusion of one of the prototypes from subsequent testing. The
      sampling characteristics of the remaining prototype sharp cut cyclone (SCC) and
      the DPMS were tested with different loading of coal dust. While the
      characteristics of the SCC remained constant, the deposited respirable coal dust
      particles altered the size-selection performance of the currently used sampler.
      This study demonstrates that the SCC performed better overall than the DPMS. 

PMID- 25060241
TI  - Aerosols and criteria gases in an underground mine that uses FAME biodiesel
      blends.
AB  - The contribution of heavy-duty haulage trucks to the concentrations of aerosols
      and criteria gases in underground mine air and the physical properties of those
      aerosols were assessed for three fuel blends made with fatty acid methyl esters
      biodiesel and petroleum-based ultra-low-sulfur diesel (ULSD). The contributions
      of blends with 20, 50, and 57% of biodiesel as well as neat ULSD were assessed
      using a 30-ton truck operated over a simulated production cycle in an isolated
      zone of an operating underground metal mine. When fueled with the B20 (blend of
      biodiesel with ULSD with 20% of biodiesel content), B50 (blend of biodiesel with
      ULSD with 50% of biodiesel content), and B57 (blend of biodiesel with ULSD with
      57% of biodiesel content) blends in place of ULSD, the truck's contribution to
      mass concentrations of elemental and total carbon was reduced by 20, 50, and 61%,
      respectively. Size distribution measurements showed that the aerosols produced by
      the engine fueled with these blends were characterized by smaller median
      electrical mobility diameter and lower peak concentrations than the aerosols
      produced by the same engine fueled with ULSD. The use of the blends resulted in
      number concentrations of aerosols that were 13-29% lower than those when ULSD was
      used. Depending on the content of biodiesel in the blends, the average reductions
      in the surface area concentrations of aerosol which could be deposited in the
      alveolar region of the lung (as measured by a nanoparticle surface area monitor)
      ranged between 6 and 37%. The use of blends also resulted in slight but
      measurable reductions in CO emissions, as well as an increase in NOX emissions.
      All of the above changes in concentrations and physical properties were found to
      be correlated with the proportion of biodiesel in the blends. 

PMID- 25060242
TI  - Transient receptor potential channel modulators as pharmacological treatments for
      lower urinary tract symptoms (LUTS): myth or reality?
AB  - Transient receptor potential (TRP) channels belong to the most intensely pursued
      drug targets of the last decade. These ion channels are considered promising
      targets for the treatment of pain, hypersensitivity disorders and lower urinary
      tract symptoms (LUTS). The aim of the present review is to discuss to what extent
      TRP channels have adhered to their promise as new pharmacological targets in the
      lower urinary tract (LUT) and to outline the challenges that lie ahead. TRP
      vanilloid 1 (TRPV1) agonists have proven their efficacy in the treatment of
      neurogenic detrusor overactivity (DO), albeit at the expense of prolonged adverse
      effects as pelvic 'burning' pain, sensory urgency and haematuria. TRPV1
      antagonists have been very successful in preclinical studies to treat pain and
      DO. However, clinical trials with the first generation TRPV1 antagonists were
      terminated early due to hyperthermia, a serious, on-target, side-effect. TRP
      vanilloid 4 (TRPV4), TRP ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) have
      important sensory functions in the LUT. Antagonists of these channels have shown
      their potential in pre-clinical studies of LUT dysfunction and are awaiting
      clinical validation. 

PMID- 25060243
TI  - Multiscale modeling of biological functions: from enzymes to molecular machines
      (Nobel Lecture).
AB  - A detailed understanding of the action of biological molecules is a pre-requisite
      for rational advances in health sciences and related fields. Here, the challenge
      is to move from available structural information to a clear understanding of the
      underlying function of the system. In light of the complexity of macromolecular
      complexes, it is essential to use computer simulations to describe how the
      molecular forces are related to a given function. However, using a full and
      reliable quantum mechanical representation of large molecular systems has been
      practically impossible. The solution to this (and related) problems has emerged
      from the realization that large systems can be spatially divided into a region
      where the quantum mechanical description is essential (e.g. a region where bonds
      are being broken), with the remainder of the system being represented on a
      simpler level by empirical force fields. This idea has been particularly
      effective in the development of the combined quantum mechanics/molecular
      mechanics (QM/MM) models. Here, the coupling between the electrostatic effects of
      the quantum and classical subsystems has been a key to the advances in describing
      the functions of enzymes and other biological molecules. The same idea of
      representing complex systems in different resolutions in both time and length
      scales has been found to be very useful in modeling the action of complex
      systems. In such cases, starting with coarse grained (CG) representations that
      were originally found to be very useful in simulating protein folding, and
      augmenting them with a focus on electrostatic energies, has led to models that
      are particularly effective in probing the action of molecular machines. The same
      multiscale idea is likely to play a major role in modeling of even more complex
      systems, including cells and collections of cells. 

PMID- 25060244
TI  - Slaughtering sacred cows: six institutional obstacles to advances in family
      planning.
AB  - In order to capitalise on new opportunities to advance contraceptive and
      reproductive health choices globally, organisations working in these fields will
      need to overcome six institutional obstacles. These are: (i) committee
      management; (ii) over-medicalisation; (iii) fear of risk and controversy; (iv)
      conferences, meetings, and symposia; (v) obsession with coordination; and (vi)
      fear of sex. The reproductive health community will require energy, innovative
      approaches, and a sharp focus on service delivery to address these hurdles that
      will otherwise slow down and misdirect programmatic momentum.

PMID- 25060245
TI  - Recovery of gastrointestinal function with thoracic epidural vs. systemic
      analgesia following gastrointestinal surgery.
AB  - The objective of this review was to systematically assess the effect of thoracic
      epidural analgesia (TEA) vs. systemic analgesia (SA) on the recovery of
      gastrointestinal (GI) function in patients following GI surgery. We performed a
      comprehensive literature search to identify randomized controlled trials of adult
      patients undergoing GI surgery, comparing the effect of two postoperative
      analgesia regimens. Patients postoperatively receiving local anesthesia-based TEA
      with or without opioids were compared to patients receiving opioid-based SA. The
      outcomes considered were times to GI function recovery, GI complications, and
      specific side effects. Twelve studies with 331 patients in the TEA group and 319
      in the SA group were included. Compared to SA, TEA improved the GI recovery after
      GI procedures by shortening the time to first passage of flatus by 31.3 h, 95%
      confidence intervals (CIs): -33.2 to -29.4, P < 0.01; and shortening the time to
      first passage of stool by 24.1 h, 95% CIs: -27.2 to -20.9, P < 0.001. There was
      no difference between the groups in the incidence of anastomotic leakage and
      ileus. The occurrence of postoperative hypotension was relatively higher in the
      TEA group, risk ratio: 7.9, 95% CIs: 2.4 to 26.5, P = 0.001; other side effects
      (such as pruritus and vomiting) were similar in the two groups. There is evidence
      that TEA (compared to SA) improves the recovery of GI function after GI
      procedures without any increased risk of GI complications. To further confirm
      these effects, larger, better quality randomized controlled trials with standard
      outcome measurements are needed. 

PMID- 25060246
TI  - Oncologic mechanical emergencies.
AB  - Prevalence of cancer and its various related complications continues to rise.
      Increasingly these life-threatening complications are initially managed in the
      emergency department, making a prompt and accurate diagnosis crucial to
      effectively institute the proper treatment and establish goals of care. The
      following oncologic emergencies are reviewed in this article: pericardial
      tamponade, superior vena cava syndrome, brain metastasis, malignant spinal cord
      compression, and hyperviscosity syndrome. 

PMID- 25060247
TI  - Oncologic metabolic emergencies.
AB  - Cancer and its therapies may lead to several metabolic emergencies that emergency
      providers (EPs) should be well-versed in identifying and managing. With prompt
      recognition and treatment initiation in the emergency department, lives can be
      saved and quality of life maintained. Most oncologic metabolic emergencies occur
      in advanced cancer states, but some follow initiation of treatment or may be the
      presenting syndrome that leads to the cancer diagnosis. This article reviews the
      2 most emergent oncologic metabolic diagnoses: tumor lysis syndrome and
      hypercalcemia of malignancy. A discussion on associated cancers and conditions,
      pathogenesis and pathophysiology, and management recommendations is included. 

PMID- 25060248
TI  - Pediatric oncologic emergencies.
AB  - The overall prognosis for most pediatric cancers is good. Mortality for all
      childhood cancers combined is approximately half what it was in 1975, and the
      survival rates of many malignancies continue to improve. However, the incidence
      of childhood cancer is significant and the related emergencies that develop
      acutely carry significant morbidity and mortality. Emergency providers who can
      identify and manage oncologic emergencies can contribute significantly to an
      improved prognosis. Effective care of pediatric malignancies requires an age
      appropriate approach to patients and compassionate understanding of family
      dynamics. 

PMID- 25060249
TI  - Neutropenic fever.
AB  - Fever is a common presenting complaint among adult or pediatric patients in the
      emergency department setting. Although fever in healthy individuals does not
      necessarily indicate severe illness, fever in patients with neutropenia may
      herald a life-threatening infection. Therefore, prompt recognition of patients
      with neutropenic fever is imperative. Serious bacterial illness is a significant
      cause of morbidity and mortality for neutropenic patients. Neutropenic fever
      should trigger the initiation of a rapid work-up and the administration of
      empiric systemic antibiotic therapy to attenuate or avoid the progression along
      the spectrum of sepsis, severe sepsis, septic shock syndrome, and death. 

PMID- 25060250
TI  - Chemotherapeutic medications and their emergent complications.
AB  - Patients with complications of chemotherapy, either acute or chronic, are
      frequently encountered in the emergency department (ED). Some patients present
      with complaints immediately after chemotherapy administration, whereas others may
      show subtle, secondary signs or may have no signs or symptoms of chemotoxicity.
      An increased index of suspicion prompts early recognition, diagnosis, and
      prevention of further iatrogenic injury. This article reviews characteristic
      hypersensitivity reactions, typical organ system dysfunction, and treatment
      strategies for adult patients who present to the ED with complications after
      chemotherapy. 

PMID- 25060251
TI  - Acute leukemia.
AB  - Although great progress has been made in the understanding and treatment of acute
      leukemia, this disease has not been conquered. For emergency providers (EPs), the
      presentation of these patients to an emergency department presents a host of
      challenges. A patient may present with a new diagnosis of leukemia or with
      complications of the disease process or associated chemotherapy. It is incumbent
      on EPs to be familiar with the manifestations of leukemia in its various stages
      and maintain some suspicion for this diagnosis, given the nebulous and insidious
      manner in which leukemia can present. 

PMID- 25060252
TI  - Myeloproliferative disorders.
AB  - The emergency providers generally encounters myeloproliferative disorders (MPNs)
      in 1 of 2 ways: as striking laboratory abnormalities of seeming unknown
      consequence, or in previously diagnosed patients presenting with complications.
      The course of patients with MPNs is highly variable, but major complications can
      arise. Emergent conditions related to hyperviscosity need to be recognized early
      and treated aggressively. Rapid hydration, transfusion, cytoreduction, and early
      hematology consultation can be lifesaving. Likewise, although management is not
      altered, a high index of suspicion for thrombotic complications is required in
      patients with known MPNs as these are a significant cause of morbidity and
      mortality. 

PMID- 25060253
TI  - Anemia.
AB  - Patients with anemia are frequently encountered in the emergency department (ED);
      emergency physicians (EPs) often play an important role in the evaluation and
      management of anemia. Although many patients have findings consistent with anemia
      on routine laboratory tests, only a small percentage will require acute
      intervention. An understanding of the broader types of anemia and how to manage
      such patients is important in the practice of an EP, as the presence of anemia
      will impact treatment plans for a variety of other disorders. This article
      reviews the evaluation and management of adult patients presenting to the ED with
      anemia. 

PMID- 25060254
TI  - Sickle cell disease in the emergency department.
AB  - Acute painful episodes are the most common reason for emergency department visits
      among patients with sickle cell disease (SCD). Early and aggressive pain
      management is a priority. Emergency providers (EPs) must also diagnose other
      emergent diagnoses in patients with SCD and differentiate them from vaso
      occlusive crisis. EPs should be aware of cognitive biases that may misdirect the
      diagnostic process. Administration of intravenous fluids should be used
      judiciously. Blood transfusion may be considered. Coordination of care with
      hematology is an important part of the effective emergency department and long
      term management of patients with SCD. 

PMID- 25060255
TI  - Thrombotic microangiopathies (TTP, HUS, HELLP).
AB  - Thrombocytopenia, strictly defined as a platelet count less than 150,000, is
      common in the emergency department. Recognition, diagnostic investigation, and
      proper disposition of a thrombocytopenic patient are imperative. One group of
      disorders leading to thrombocytopenia is the thrombotic microangiopathies,
      hallmarked by platelet destruction. These thrombotic microangiopathies include
      thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and
      hemolysis, elevated liver enzyme levels, low platelet count (HELLP), which should
      be distinguished from similar disease processes such as immune thrombocytopenia
      (ITP), disseminated intravascular coagulation (DIC) and heparin induced
      thrombocytopenia (HIT). In this article, clinical presentations, pathophysiology,
      diagnostic workup, management plans, complications, and dispositions are
      addressed for this complex group of platelet disorders. 

PMID- 25060256
TI  - Evaluation and management of congenital bleeding disorders.
AB  - Patients presenting to the emergency department with acute bleeding and a history
      of clotting or platelet disorder present a unique challenge to the emergency
      physician. The severity of bleeding presentation is based on mechanism as well as
      factor levels: patients with factor levels greater than 5% can respond to most
      minor hemostatic challenges, whereas those with factor levels less than 1% bleed
      with minor trauma or even spontaneously. Treatment should be initiated in
      consultation with the patient's hematologist using medications and specific
      factor replacement, except in rare, life-threatening, resource-poor situations,
      when cryoprecipitate or activated prothrombin complex may be considerations. 

PMID- 25060257
TI  - Acquired bleeding disorders.
AB  - Emergency medicine practitioners treat bleeding patients on a regular basis.
      Disorders of hemostasis are an additional challenge in these patients but can be
      assessed and managed in a systematic fashion. Of particular importance to the
      emergency clinician are the iatrogenic causes of abnormal hemostasis. Other
      acquired causes of abnormal hemostasis include renal disease, immune
      thrombocytopenia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome,
      acquired coagulation factor inhibitors, acute traumatic coagulopathy, liver
      disease, and disseminated intravascular coagulopathy. 

PMID- 25060258
TI  - Antithrombotic reversal agents.
AB  - The actively bleeding anticoagulated patient presenting to the emergency
      department requires rapid evaluation and treatment, which is made increasingly
      complicated by the ever-evolving antithrombotic treatment options used in
      medicine. Even with excellent supportive care, the timeliness with which reversal
      decisions need to be made continues to demand of the emergency practitioner a
      familiarity with the properties and general characteristics of a variety of
      antithrombotic agents. Reversal options vary and may include vitamin K, FFP, PCC,
      rFVIIa, platelets, and desmopressin, among others. 

PMID- 25060259
TI  - Blood product transfusions and reactions.
AB  - Blood product transfusions are an essential component of the practice of
      emergency medicine. From acute traumatic hemorrhage to chronic blood loss
      necessitating transfusion for symptomatic anemia, familiarity with individual
      blood products and their indications for transfusion is an essential tool for
      every emergency physician (EP). Although the focus of this article is primarily
      on the transfusion of red blood cells, many of the concepts are applicable to the
      transfusion of all blood products. EPs must be fully familiar with both the
      individual blood components and the potential reactions and complications of
      these transfusions. 

PMID- 25060260
TI  - Hematology/oncology emergencies.

PMID- 25060261
TI  - Hematology/oncology emergencies.

PMID- 25060263
TI  - Foreward. Consanguinity and genomics.

PMID- 25060264
TI  - Consanguinity in the contemporary world.

PMID- 25060265
TI  - Marriage patterns and reproductive decision-making in the inhabitants of a single
      Muslim village during a 50-year period.
AB  - OBJECTIVES: In a single Muslim village in Israel, established about 300 years ago
      by a small number of founders, a longitudinal study was conducted on the types of
      marriages and their effects on family planning, with the age at which a woman had
      her first child and the size of the family assessed. METHODS: The information for
      the analysis was extracted from a detailed database including individuals
      residing in and originating from the village. RESULTS: A shift from the practice
      of marrying a close relative, in particular patrilateral parallel first-cousin
      marriages, to marrying a more remotely related individual was observed during the
      study period. Another major change was a significant reduction in the mean number
      of children born per woman from 8.7 among women born between 1930 and 1939 to 4.7
      among those born between 1960 and 1969. In families in which the parents were
      biological relatives, the number of children was always higher than in families
      in which the parents were unrelated. The mean age of the mother at the birth of
      her first child progressively increased during the study period from 20.9 to 23.7
      years. The maternal age was always higher when the spouses were from different
      villages than when they were biological relatives, either being first cousins or
      more distantly related. CONCLUSIONS: Significant sociodemographic changes were
      observed during the course of the last 50 years. However, the consequences of the
      long-lasting isolation of the population remain and still exert an important
      effect on present-day medical problems in the village.

PMID- 25060266
TI  - Consanguineous marriage, reproductive behaviour and postnatal mortality in
      contemporary Iran.
AB  - OBJECTIVES: The aims of the study were to determine the prevalence, types and
      socio-economic correlates of consanguineous marriages in Iran, and to gauge the
      extent to which consanguinity influenced fertility, pregnancy outcomes and the
      expression of genetic disorders in the present-day population. METHODS: Data on
      the prevalence of consanguinity and birth outcomes in the first marriages of
      5,515 women were abstracted from the 2005 Iran Low Fertility Study [Hosseini
      Chavoshi et al: Fertility and Contraceptive Use Dynamics in Iran: Special Focus
      on Low Fertility Regions. Canberra, Australian National University, 2007]. The
      results of associated socio-economic variables were collated and assessed by
      Pearson's chi(2) analysis and logistic regression. RESULTS: Overall, 37.4% of the
      marriages were consanguineous (alpha = 0.0149), but with major differences
      between 4 representative populations. Consanguinity was higher among rural
      couples, older marriage cohorts, women marrying at a younger age, and women with
      lower levels of formal education. In general, consanguineous couples had higher
      mean numbers of pregnancies, live births and surviving children. CONCLUSIONS:
      Given declining family sizes, a rapid urbanization and increased educational and
      employment opportunities, it seems inevitable that consanguineous marriages will
      decline in prevalence in Iran, albeit more slowly in more traditional rural
      communities. Predictably, there will be a concomitant reduction in the incidence
      of recessive genetic disorders, but this is against a background transition from
      communicable to non-communicable diseases.

PMID- 25060267
TI  - Drivers of cousin marriage among British Pakistanis.
AB  - BACKGROUND/AIM: Why has the apparently high rate of cousin marriage among
      Bradford Pakistanis been sustained, 50 years since Pakistani migration to Britain
      began? METHODS: A review of the anthropological literature on Pakistani migration
      and settlement, British Pakistani marriage patterns and the phenomenon of
      transnational marriage. RESULTS: British Pakistanis are diverse in regional
      origins and social class characteristics, with many Bradford Pakistanis
      originating from the Mirpur district and northern Punjab. British Pakistani
      marriages often involve a partner from Pakistan who joins a spouse in the UK.
      Transnational marriage of first cousins offers relatives in Pakistan
      opportunities for a 'better' life in the West and are important for British
      Pakistanis for economic, social, cultural and emotional reasons. These processes
      are also differentially influenced by region of origin and class characteristics
      in Pakistan as well as by education, employment and locality in Britain. The
      pattern observed in Bradford may not be applicable nationally. CONCLUSION:
      Further research examining marital decisions over several generations in families
      differing by social class, region of origin in Pakistan and locality in Britain
      is necessary to contextualise the findings from Bradford.

PMID- 25060262
TI  - Convergence of nanotechnology and cancer prevention: are we there yet?
AB  - Nanotechnology is emerging as a promising modality for cancer treatment; however,
      in the realm of cancer prevention, its full utility has yet to be determined.
      Here, we discuss the potential of integrating nanotechnology in cancer prevention
      to augment early diagnosis, precision targeting, and controlled release of
      chemopreventive agents, reduced toxicity, risk/response assessment, and
      personalized point-of-care monitoring. Cancer is a multistep, progressive
      disease; the functional and acquired characteristics of the early precancer
      phenotype are intrinsically different from those of a more advanced anaplastic or
      invasive malignancy. Therefore, applying nanotechnology to precancers is likely
      to be far more challenging than applying it to established disease. Frank cancers
      are more readily identifiable through imaging and biomarker and histopathologic
      assessment than their precancerous precursors. In addition, prevention subjects
      routinely have more rigorous intervention criteria than therapy subjects. Any
      nanopreventive agent developed to prevent sporadic cancers found in the general
      population must exhibit a very low risk of serious side effects. In contrast, a
      greater risk of side effects might be more acceptable in subjects at high risk
      for cancer. Using nanotechnology to prevent cancer is an aspirational goal, but
      clearly identifying the intermediate objectives and potential barriers is an
      essential first step in this exciting journey.

PMID- 25060269
TI  - Inbreeding coefficient estimation with dense SNP data: comparison of strategies
      and application to HapMap III.
AB  - BACKGROUND/AIMS: If the parents of an individual are related, it is possible for
      the individual to have received at 1 locus 2 identical-by-descent alleles that
      are copies of a single allele carried by the parents' common ancestor. The
      inbreeding coefficient measures the probability of this event and increases with
      increasing relatedness between the parents. It is traditionally computed from the
      observed inbreeding loops in the genealogies and its accuracy thus depends on the
      depth and reliability of the genealogies. With the availability of genome-wide
      genetic data, it has become possible to compute a genome-based inbreeding
      coefficient f, and different methods have been developed to estimate f and
      identify inbred individuals in a sample from the observed patterns of
      homozygosity at markers. METHODS: For this paper, we performed simulations with
      known genealogies using different SNP panels with different levels of linkage
      disequilibrium (LD) to compare several estimators of f, including single-point
      estimates, methods based on the length of runs of homozygosity (ROHs) and
      different methods that use hidden Markov models (HMMs). We also compared the
      performances of some of these estimators to identify inbred individuals in a
      sample using either HMM likelihood ratio tests or an adapted version of the ERSA
      software. RESULTS: Single-point methods were found to have higher standard
      deviations than other methods. ROHs gave the best estimates provided the correct
      length threshold is known. HMMs on sparse data gave equivalent or better results
      than HMMs modeling LD. Provided LD is correctly accounted for, the inbreeding
      estimates were very similar using the different SNP panels. The HMM likelihood
      ratio tests were found to perform better at detecting inbred individuals in a
      sample than the adapted ERSA. All methods accurately detected inbreeding up to
      second-cousin offspring. We applied the best method on release 3 of the HapMap
      phase III project, found up to 4% of inbred individuals, and created HAP1067, an
      unrelated and outbred dataset of this release. CONCLUSIONS: We recommend using
      HMMs on multiple sparse maps to estimate and detect inbreeding in large samples.
      If the sample of individuals is too small to estimate allele frequencies, we
      advise to estimate them on reference panels or to use 1,500-kb ROHs. Finally, we
      suggest to investigators using HapMap to be careful with inbred individuals,
      especially in the GIH (Gujarati Indians from Houston in Texas) population.

PMID- 25060268
TI  - Population-genetic influences on genomic estimates of the inbreeding coefficient:
      a global perspective.
AB  - BACKGROUND/AIMS: Culturally driven marital practices provide a key instance of an
      interaction between social and genetic processes in shaping patterns of human
      genetic variation, producing, for example, increased identity by descent through
      consanguineous marriage. A commonly used measure to quantify identity by descent
      in an individual is the inbreeding coefficient, a quantity that reflects not only
      consanguinity, but also other aspects of kinship in the population to which the
      individual belongs. Here, in populations worldwide, we examine the relationship
      between genomic estimates of the inbreeding coefficient and population patterns
      in genetic variation. METHODS: Using genotypes at 645 microsatellites, we compare
      inbreeding coefficients from 5,043 individuals representing 237 populations
      worldwide to demographic consanguinity frequency estimates available for 26
      populations as well as to other quantities that can illuminate population-genetic
      influences on inbreeding coefficients. RESULTS: We observe higher inbreeding
      coefficient estimates in populations and geographic regions with known high
      levels of consanguinity or genetic isolation and in populations with an increased
      effect of genetic drift and decreased genetic diversity with increasing distance
      from Africa. For the small number of populations with specific consanguinity
      estimates, we find a correlation between inbreeding coefficients and
      consanguinity frequency (r = 0.349, p = 0.040). CONCLUSIONS: The results
      emphasize the importance of both consanguinity and population-genetic factors in
      influencing variation in inbreeding coefficients, and they provide insight into
      factors useful for assessing the effect of consanguinity on genomic patterns in
      different populations.

PMID- 25060270
TI  - Detection of runs of homozygosity from whole exome sequencing data: state of the
      art and perspectives for clinical, population and epidemiological studies.
AB  - Runs of homozygosity (ROH) are sizeable stretches of homozygous genotypes at
      consecutive polymorphic DNA marker positions, traditionally captured by means of
      genome-wide single nucleotide polymorphism (SNP) genotyping. With the advent of
      next-generation sequencing (NGS) technologies, a number of methods initially
      devised for the analysis of SNP array data (those based on sliding-window
      algorithms such as PLINK or GERMLINE and graphical tools like HomozygosityMapper)
      or specifically conceived for NGS data have been adopted for the detection of ROH
      from whole exome sequencing (WES) data. In the latter group, algorithms for both
      graphical representation (AgileVariantMapper, HomSI) and computational detection
      (H(3)M(2)) of WES-derived ROH have been proposed. Here we examine these different
      approaches and discuss available strategies to implement ROH detection in WES
      analysis. Among sliding-window algorithms, PLINK appears to be well-suited for
      the detection of ROH, especially of the long ones. As a method specifically
      tailored for WES data, H(3)M(2) outperforms existing algorithms especially on
      short and medium ROH. We conclude that, notwithstanding the irregular
      distribution of exons, WES data can be used with some approximation for unbiased
      genome-wide analysis of ROH features, with promising applications to homozygosity
      mapping of disease genes, comparative analysis of populations and epidemiological
      studies based on consanguinity.

PMID- 25060271
TI  - Admixture and clinical phenotypic variation.
AB  - All human populations exhibit some level of genetic differentiation. This
      differentiation, or population stratification, has many interacting sources,
      including historical migrations, population isolation over time, genetic drift,
      and selection and adaptation. If differentiated populations remained isolated
      from each other over a long period of time such that there is no mating of
      individuals between those populations, then some level of global consanguinity
      within those populations will lead to the formation of gene pools that will
      become more and more distinct over time. Global genetic differentiation of this
      sort can lead to overt phenotypic differences between populations if
      phenotypically relevant variants either arise uniquely within those populations
      or begin to exhibit frequency differences across the populations. This can occur
      at the single variant level for monogenic phenotypes or at the level of aggregate
      variant frequency differences across the many loci that contribute to a phenotype
      with a multifactorial or polygenic basis. However, if individuals begin to
      interbreed (or 'admix') from populations with different frequencies of
      phenotypically relevant genetic variants, then these admixed individuals will
      exhibit the phenotype to varying degrees. The level of phenotypic expression will
      depend on the degree to which the admixed individuals have inherited causative
      variants that have descended from the ancestral population in which those
      variants were present (or, more likely, simply more frequent). We review studies
      that consider the association between the degree of admixture (or ancestry) and
      phenotypes of clinical relevance. We find a great deal of literature-based
      evidence for associations between the degree of admixture and phenotypic
      variation for a number of admixed populations and phenotypes, although not all
      this evidence is confirmatory. We also consider the implications of such
      associations for gene-mapping initiatives as well as general clinical
      epidemiology studies and medical practice. We end with some thoughts on the
      future of studies exploring phenotypic differences among admixed individuals as
      well as individuals with different ancestral backgrounds.

PMID- 25060272
TI  - The effect of consanguinity on neonatal outcomes and health.
AB  - Consanguineous marriages constitute a significant fraction of marriages worldwide
      and confer a major public health concern on newborns. In addition to the risk of
      acquiring a recessive genetic disease, the offspring of consanguineous parents
      are plausibly at an increased risk of preterm birth, decreased anthropometric
      measurements, congenital defects and mortality. How consanguinity confers such an
      increased risk is still largely unknown. In this review, we discuss the effect of
      consanguinity on selected gestational outcomes by delineating the different
      studies that have led to such findings. We also investigate the different
      conclusions that have emerged regarding the effect of consanguinity on
      gestational outcomes.

PMID- 25060273
TI  - Consanguinity and dysmorphology in Arabs.
AB  - Incidence rates of congenital disorders among the 350 million inhabitants of Arab
      countries could be influenced via the people's demographic and cultural
      characteristics. Arabs usually marry at a young age and have large families. They
      share certain core cultural values and beliefs, with the family accepted as the
      central structure of society. Consanguineous marriage is favored and respected in
      most if not all Arab communities, and intrafamilial unions currently account for
      20-50% of all marriages. First-cousin unions are especially popular and
      constitute almost one quarter of all marriages in many Arab countries.
      Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a
      considerable proportion of all birth defects among Arabs. Arab geneticists, with
      their persistent commitment to advancing research, have contributed to the
      description of a number of rare and new AR syndromes with the identification of
      novel genes. The collaboration with research teams in high-income countries
      resulted in a plethora of data on pathogenic variants and their function in
      causing dysmorphic syndromes. There could still be a considerable number of rare
      dysmorphic syndromes that prevail among Arabs which are not hitherto described
      and whose underlying molecular pathologies are not yet defined. Arab countries
      should thus strive to deploy DNA diagnostics and to build research capability
      around local priorities. Furthermore, a characterization of the prevailing
      genetic disorders in each geographic location, together with their mutations, is
      needed to plan for appropriate screening and testing protocols. An overview of
      consanguinity in Arab countries and examples of dysmorphology syndromes
      associated with consanguinity with their available molecular bases will be
      discussed.

PMID- 25060274
TI  - Consanguinity and disorders of sex development.
AB  - Disorders of sex development (DSD) are defined as 'congenital conditions in which
      the development of chromosomal, gonadal, or anatomical sex is atypical' [Lee et
      al., Pediatrics 2006;118:e488-e500]. Studies conducted in Western countries, with
      low rates of consanguinity, show that truly ambiguous genitalia have an estimated
      incidence of 1:5,000 births. There are indications that the prevalence of DSD is
      higher in endogamous communities. The incidence of ambiguous genitalia in Saudi
      Arabia has been estimated at 1:2,500 live births; whilst in Egypt, it has been
      estimated at 1:3,000 live births. This may be due in part to an increase in
      disorders of androgen synthesis associated with 46,XX DSD. There is clearly a
      need for further studies to address the frequency of DSD in communities with high
      levels of consanguinity. This will be challenging, as an accurate diagnosis is
      difficult and expensive even in specialized centres. In developing countries with
      high levels of consanguinity, these limitations can be compounded by cultural,
      social and religious factors. Overall there is an indication that consanguinity
      may lead to an increase in incidences of both 46,XY and 46,XX DSD, and a co
      ordinated study of populations with higher incidences of consanguinity/endogamy
      is needed to resolve this.

PMID- 25060275
TI  - The use of autozygosity mapping and next-generation sequencing in understanding
      anterior segment defects caused by an abnormal development of the lens.
AB  - The formation of the anterior segment of the eye is an intricate process that is
      dependent to a large degree on the normal development of the lens. Despite
      intensive study of the role of well-described eye genes, many causes of
      lenticular and anterior segment anomalies remain elusive. The majority of genes
      implicated thus far act in an autosomal dominant manner. Autosomal recessive
      causes are less well described; their diagnosis has been hindered by
      technological limitations, extreme genetic heterogeneity, a lack of understanding
      of eye biology and the role of many genes within the genome. The opportunity for
      the discovery of extremely rare autosomal recessive causes of ocular
      abnormalities from the study of consanguineous families is large, particularly
      through the powerful combination of next-generation sequencing with autozygosity
      mapping. Having begun to overcome the genetic heterogeneity bottleneck, it is
      increasingly recognised that the interpretation of genetic variants and the
      association of novel genes with a particular phenotype remain challenging.
      Nonetheless, increasing understanding of the genetic and mutational basis of lens
      and anterior segment abnormalities will be of enormous value to our comprehension
      of eye disease(s). Further, it will improve our ability to accurately interpret
      putative disease-causing variants with the aim of providing more personalised
      patient care and avoiding lifelong visual loss in children.

PMID- 25060276
TI  - Consanguinity and primary immunodeficiencies.
AB  - Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders
      caused by defects in the immune system that predispose patients to infections,
      autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are
      inherited in an autosomal recessive pattern; therefore, they are more common in
      areas with high rates of consanguineous marriage. Reports about PIDs from these
      areas have demonstrated a peculiar prevalence of more severe forms of diseases
      compared to other regions, and patients born to consanguineous parents have
      increased rates of morbidity and mortality compared to other patients.
      Individuals at high risk of having a child with a PID who wish to have a healthy
      child have limited options, these include prenatal diagnosis and pre-implantation
      genetic diagnosis. However, these options require a collaborative team of
      specialists and may not always be implemented due to geographic, religious,
      financial or social factors. The recent introduction of newborn-screening
      programs for a number of T and B lymphocyte deficiencies will facilitate early
      diagnosis and therapeutic interventions, which may include hematopoietic stem
      cell transplantation and intravenous immunoglobulin treatment. There is a need
      for the implementation of strategies to increase public awareness of the health
      risks associated with consanguineous marriage. It should be stressed that genetic
      counseling should be an important component of the care of patients with PIDs as
      well as their families.

PMID- 25060277
TI  - Consanguinity and polygenic diseases: a model for antibody deficiencies.
AB  - Primary immunodeficiencies represent a heterogeneous group of disorders of the
      immune system, predisposing to various types of infections. Among them, common
      variable immunodeficiency is the most common symptomatic antibody deficiency. It
      includes several different forms characterized by defects in the terminal stage
      of B lymphocyte differentiation, leading to markedly reduced immunoglobulin serum
      levels and increased susceptibility to bacterial infections. The clinical
      phenotype is complex, including autoimmunity, granulomatous inflammation,
      lymphoproliferative disorders and malignancies. Rare autosomal recessive
      mutations in a number of single genes have recently been reported. However, the
      underlying genetic defects remain unknown in the majority of cases. In order to
      seek new genes responsible for the disease, we studied a consanguineous Italian
      family through exome sequencing combined with homozygosity mapping. Six missense
      homozygous variants passed our filtering selection and at least two of them were
      associated with some aspects of the pathological phenotype. Our data remark the
      complexity of immune system disorders and emphasize the difficulty to understand
      the significance of genetic results and their correlation with the disease
      phenotype.

PMID- 25060278
TI  - Identifying genes responsible for intellectual disability in consanguineous
      families.
AB  - Consanguinity is an important determinant of birth defects including intellectual
      disability (ID). Consanguineous populations have a relative high prevalence of
      autosomal recessive forms of intellectual disability (ARID), which constitute a
      highly heterogeneous group of disorders both in their clinical presentation and
      in their genetic aetiology. The availability of large cohorts of consanguineous
      families and the advent of next-generation sequencing techniques is currently
      accelerating the pace of gene identification in ARID. Because of the extreme
      heterogeneity, it is anticipated that hundreds of ARID (candidate) genes will be
      identified in the near future. With this robust progress, the proof of causality
      of the identified candidate genes is challenging. To this end, genetic
      recurrence, cellular assays and animal modelling would serve as three non
      exclusive strategies, in order to assign causality to a certain gene. Extensive
      genetic investigations in consanguineous populations will help in reducing the
      total disease burden through proper genetic counselling. Moreover, such findings
      will be helpful to elucidate different pathways and further for possible
      therapeutic interventions.

PMID- 25060279
TI  - Consanguinity and endogamy in the Netherlands: demographic and medical genetic
      aspects.
AB  - This paper reviews what is currently known about the presence of consanguinity
      and endogamy in the Netherlands, in the past and today, and concludes with a
      discussion of medical genetic aspects. First geographic characteristics, the
      demographic history, the genetic make-up of the native population, legal aspects
      and the public opinion are reviewed. Then data on the prevalence of consanguinity
      in the native population are presented for marriages since 1840, followed by data
      on consanguineous marriages among immigrants from countries with a tradition of
      close-kin marriages. It is estimated that approximately 1% of at-risk
      consanguineous couples are referred to clinical genetic centres for prospective
      genetic counselling in the Netherlands. This picture will change dramatically if
      and when next-generation sequencing is introduced to identify couples at >= 25%
      risk prospectively.

PMID- 25060280
TI  - Specific aspects of consanguinity: some examples from the Tunisian population.
AB  - Located at the cross-road between Europe and Africa, Tunisia is a North African
      country of 11 million inhabitants. Throughout its history, it has been invaded by
      different ethnic groups. These historical events, and consanguinity, have
      impacted on the spectrum and frequency of genetic diseases in Tunisia.
      Investigations of Tunisian families have significantly contributed to elucidation
      of the genetic bases of rare disorders, providing an invaluable resource of cases
      due to particular familial structures (large family size, consanguinity and share
      of common ancestors). In the present study, we report on and review different
      aspects of consanguinity in the Tunisian population as a case study, representing
      several features common to neighboring or historically related countries in North
      Africa and the Middle East. Despite the educational, demographic and behavioral
      changes that have taken place during the last four decades, familial and
      geographical endogamy still exist at high frequencies, especially in rural areas.
      The health implications of consanguinity in Tunisian families include an
      increased risk of the expression of autosomal recessive diseases and particular
      phenotypic expressions. With new sequencing technologies, the investigation of
      consanguineous populations provides a unique opportunity to better evaluate the
      impact of consanguinity on the genome dynamic and on health, in addition to a
      better understanding of the genetic bases of diseases.

PMID- 25060282
TI  - Consanguinity, endogamy and inborn errors of metabolism in Oman: a cross
      sectional study.
AB  - The Sultanate of Oman, like many other Arab countries, has relatively high rates
      of consanguinity. Reports suggest that the incidence of inborn errors of
      metabolism (IEM) is also high in Oman. This retrospective cross-sectional study
      was designed to evaluate the number of patients with IEM being followed at the
      only two tertiary centers in Oman treating such patients, and to calculate the
      consanguinity rates among these families. The electronic medical records of all
      patients were reviewed for demographic and clinical characteristics. A total of
      285 patients with IEM were being followed at the 2 centers involved; 162 (56.8%)
      were male and 123 (43.2%) were female. The history of consanguinity was
      documented or available for 241 patients: 229 patients (95%) were born to
      consanguineous parents related as second cousins or closer. First-cousin
      marriages were reported in 191 families (79.3%), while 31 patients (12.9%) were
      born to second cousins. The parents of 5 patients (2%) were related as double
      first cousins, and 2 patients (1%) were born to first cousins once removed. The
      average coefficient of inbreeding (F) in our study was 0.081. Seventeen patients
      (6%) had associated comorbid conditions other than IEM. Our study highlights the
      clinical burden of IEM in Oman and emphasizes the high consanguinity rates among
      the parents of affected patients.

PMID- 25060281
TI  - Consanguinity and hereditary hearing loss in Qatar.
AB  - Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula
      in the Persian Gulf. Its native population consists of 3 major subgroups: people
      of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and
      individuals with African admixture. Historically, all types of consanguineous
      marriages have been and still are common in the Qatari population, particularly
      among first and double-first cousins. Thus, there is a higher risk for most
      inherited diseases including hereditary hearing loss (HHL). In particular, a
      hearing loss prevalence of 5.2% has been reported in Qatar, with parental
      consanguinity being more common among affected individuals as compared with
      unaffected ones. Our recent molecular results confirm a high homogeneity and
      level of inbreeding in Qatari HHL patients. Among all HHL genes, GJB2, the major
      player worldwide, accounts for a minor proportion of cases and at least 3
      additional genes have been found to be mutated in Qatari patients. Interestingly,
      one gene, BDP1, has been described to cause HHL only in this country. These
      results point towards an unexpected level of genetic heterogeneity despite the
      high level of inbreeding. This review provides an up-to-date picture of HHL in
      Qatar and of the impact of consanguinity on this disease.

PMID- 25060283
TI  - A community-based study of mucopolysaccharidosis type VI in Brazil: the influence
      of founder effect, endogamy and consanguinity.
AB  - Mucopolysaccharidosis type VI (MPS VI - Maroteaux-Lamy syndrome) is a globally
      rare lysosomal storage disease caused by a deficiency of arylsulfatase B.
      However, in Monte Santo, a poor and isolated rural region in Northeast Brazil
      with large family sizes and high rates of community endogamy and parental
      consanguinity (alpha = 0.00483), 9 living and 4 now deceased individuals in 11
      kindreds have been diagnosed with MPS VI, all with the same p.H178L missense
      founder mutation. A further 33 deceased persons have been identified by family
      members as exhibiting the disease phenotype. Detailed pedigrees were constructed
      for the 13 genomically confirmed MPS VI patients, with blood samples collected
      from 236 unaffected family members to determine the prevalence of the p.H178L
      mutation. A total of 98 (20.8%) mutant alleles and 374 (79.2%) normal alleles
      were identified, with 41.5% of the individuals heterozygous for the p.H178L
      mutation and 58.5% homozygous for the normal allele. A significant number of
      other family members with a 50 or 25% chance of being heterozygous for the
      p.H178L mutation were unavailable for testing. The data indicate a compelling
      case for community-based neonatal screening in conjunction with further
      initiatives among MPS VI family members to promote genetic education and genetic
      counselling.

PMID- 25060284
TI  - Investigating the potential effect of consanguinity on type 2 diabetes
      susceptibility in a Saudi population.
AB  - OBJECTIVE: To examine mechanisms by which consanguinity might increase the risk
      of type 2 diabetes (T2D) in a Saudi population. METHODOLOGY: 362 adult male
      participants were recruited, 179 were T2D patients and 183 healthy siblings. T2D
      severity was assessed in patients by recording age at diagnosis. In healthy
      subjects, diabetes risk was studied by measuring the body mass index, fasting
      blood glucose (FBG) level, and waist circumference. Extended pedigrees were
      constructed to calculate inbreeding coefficients. To account for tribal
      relatedness degrees reported in the constructed pedigrees, assumed inbreeding
      coefficients for tribal relatedness were added to the calculated inbreeding
      coefficients. A total of 23 SNPs associated with a higher risk of T2D were
      genotyped. Results : A significant inverse association was detected between
      inbreeding coefficients and age at diagnosis (Spearman's coefficient: -0.186, p =
      0.013). In 42 families, we were able to recruit 2 healthy siblings. Pearson's
      correlation coefficient of FBG between siblings was 0.317 (p = 0.04). The
      correlation between the siblings' FBG increased with an increasing degree of
      consanguinity. The effect of consanguinity on the FBG level was further assessed
      by regression line analysis and by controlling for differences in age, caloric
      intake, and level of physical activity (beta: -0.118, p = 0.024). No significant
      association between the number of T2D risk alleles and the traits was found.
      CONCLUSION: Our findings suggest that consanguinity might increase the risk of
      T2D by an earlier onset of the disease and by strengthening possible genetic
      effects on FBG.

PMID- 25060285
TI  - Consanguinity and prevalence patterns of inherited disease in the UK Pakistani
      community.
AB  - OBJECTIVES: The aim of this paper is to describe the current knowledge about
      inherited diseases in UK children of Pakistani origin, who now number over
      300,000, and to investigate disease associations with parental consanguinity.
      METHODS: Published data on the overall prevalence of inherited diseases were
      reviewed in conjunction with published and unpublished information from the city
      of Bradford where there is a large resident Pakistani community. RESULTS: There
      is significant literature on infant mortality, congenital anomalies, disabilities
      and many clinical conditions, often drawing attention to ethnic variations and an
      increased disease prevalence in UK Pakistani children. A further analysis is
      frequently necessary to differentiate both between genetic and non-genetic
      causes, and Pakistani and non-Pakistani children, who collectively have been
      labelled as 'Asian' or 'South Asian'. CONCLUSIONS: The analysis suggests that
      much of the increased mortality and morbidity in UK Pakistani children is due to
      autosomal recessive conditions. Evidence suggests that this finding is associated
      with the custom of consanguineous marriage, but future studies might also explore
      the role of community endogamy. Prevalence data from the first and second post
      migration generations could additionally be useful in informing health planning
      in Pakistan.

PMID- 25060286
TI  - Detection and reporting of homozygosity associated with consanguinity in the
      clinical laboratory.
AB  - The detection of consanguinity by the presence of multiple regions of
      homozygosity (ROH) is not an uncommon occurrence in clinical laboratories
      performing SNP microarray analysis. Reporting practices amongst laboratories are
      highly variable, due in part to differences in testing platforms, threshold
      parameters, language utilized, and laboratory policies. While guidance documents
      have provided a framework for detection and reporting practices, and will
      doubtless serve to harmonize the field, there are still many facets of the
      testing that remain at the discretion of the performing laboratory. Clinician and
      patient education remain a high priority. In the clinical laboratory, these
      homozygous segments are often examined to identify genes associated with a
      phenotype that matches that of the proband and autosomal recessive inheritance.
      While the detection of these ROH is possible with whole genome sequencing, it
      currently requires special algorithms be utilized, an uncommon practice in most
      clinical laboratories currently performing this type of testing.

PMID- 25060287
TI  - Value of whole exome sequencing for syndromic retinal dystrophy diagnosis in
      young patients.
AB  - BACKGROUND: Several retinal dystrophies are associated with syndromic features
      including such conditions as Bardet-Biedl and Joubert syndromes. Cohen syndrome
      is an autosomal recessive disorder associated with multiple clinical
      manifestations including developmental delay, acquired microcephaly, myopia,
      pigmentary retinopathy, joint hypermobility, truncal obesity, friendly
      disposition and intermittent neutropenia. In young patients, diagnosis is
      difficult, because several of the characteristic features may not be present
      until school age or later years and the intermittent neutropenia is not always
      detectable. DESIGN: This was a prospective study using whole exome sequencing in
      syndromic retinal dystrophy. It was undertaken in a hospital and research
      institute setting. PARTICIPANTS: Participants in this study were members of a
      consanguineous Australian family of Lebanese ethnicity with two siblings with
      retinal dystrophy, microcephaly and developmental delay. METHODS: Detailed
      clinical evaluation was undertaken. Whole exome capture and sequencing of patient
      genomic DNA samples was followed by sequence alignment, variant detection,
      comparison and prioritization. MAIN OUTCOME MEASURES: Pathogenic variant
      identification in the disease-causing gene in affected individuals. RESULTS: We
      identified a novel homozygous deletion leading to a frameshift mutation in
      VPS13B, c.11327del, p.(Asn3776Thrfs*102), the disease gene associated with Cohen
      syndrome. CONCLUSIONS: This report emphasizes the value of a broad-based whole
      exome sequencing approach in disease gene identification in the syndromic retinal
      dystrophies, where all disease characteristics may not be present in young
      patients to allow a clinical diagnosis. This facilitates improved prognostic and
      genetic information for patients and families.

PMID- 25060288
TI  - Main outcomes of the Move More for Life Trial: a randomised controlled trial
      examining the effects of tailored-print and targeted-print materials for
      promoting physical activity among post-treatment breast cancer survivors.
AB  - BACKGROUND: Participation in physical activity can improve the health outcomes of
      breast cancer survivors. To impact public health, broad-reaching sustainable
      interventions that promote physical activity are needed. PURPOSE: To evaluate the
      efficacy of two distance-based interventions for promoting physical activity
      among breast cancer survivors compared with a standard recommendation control.
      METHODS: Breast cancer survivors who had finished 'active' cancer treatment were
      eligible to participate. Participants (n = 330) were randomly assigned to receive
      one of the following mail-delivered interventions: three computer-tailored
      newsletters, a previously developed breast cancer-specific physical activity
      booklet or a pamphlet detailing the public health recommendations for physical
      activity (control). Primary outcomes were self-reported moderate to vigorous
      aerobic activity and participant's self-reported resistance training activity at
      4 months post-baseline. Secondary outcomes were pedometer step counts, whether or
      not participants were meeting the physical activity guidelines, time spent in
      sedentary behaviour, fatigue and health-related quality of life. RESULTS:
      Participants randomised into the tailored-print intervention group were three
      times more likely to commence resistance training and meet the resistance
      training guidelines immediately after the intervention than participants
      allocated to the control group. There were no other significant intervention
      effects. CONCLUSION: Computer-tailored newsletters may be an effective strategy
      for enhancing resistance-based physical activity among breast cancer survivors.
      The null findings relating to other outcomes may be due to ceiling effects (in
      the case of aerobic activity, fatigue and health-related quality of life) or the
      sensitivity of the measure used (in the case of sitting time). These issues
      require further exploration.

PMID- 25060289
TI  - A statewide assessment of youth sports- and recreation-related injuries using
      emergency department administrative records.
AB  - PURPOSE: Adequate levels of physical activity are essential for health, but
      participation in sports and recreational physical activities is associated with
      an increased risk of injury. The present study quantifies the impact of sports-
      and recreation-related injuries (SRIs) for middle and high school-aged Kentucky
      children. METHODS: The study describes unintentional injuries in 2010-2012
      Kentucky emergency department (ED) administrative records for patients age 10-18
      years. SRIs were identified based on external codes of injuries, according to the
      International Classification of Diseases, Ninth Revision, Clinical Modification.
      RESULTS: A total of 163,252 ED visits by 10- to 18-year olds occurred during the
      study period, of which 31,898 (20%) were related to participation in physical
      activity. Males accounted for 70% of the SRIs. The primary mechanisms for SRIs
      were strikings (55%), falls (26%), and overexertion (13%). Superficial contusions
      (25%), sprains/strains (33%), and fractures (18%) were the primary diagnoses. The
      total charges billed for SRIs exceeded $40 million, or 19% of the total charges
      billed for all unintentional injury-related ED visits in this age group.
      CONCLUSIONS: The present study revealed one fifth of all Kentucky ED visits, and
      ED charges billed for unintentional injury among youth aged 10-18 years were
      related to sport and recreation. In the absence of a dedicated SRI surveillance
      system, ED administrative records provide meaningful utility for conducting
      statewide assessments of adolescent SRIs.

PMID- 25060290
TI  - Positive attributes protect adolescents from risk for the metabolic syndrome.
AB  - PURPOSE: Risk for cardiovascular disease develops as early as adolescence. The
      primary objective of the present study was to identify whether low levels of
      positive and high levels of negative emotions and attitudes are associated with
      the combination of cardiovascular risk factors known as the metabolic syndrome.
      METHODS: Participants were 239 healthy adolescents (57% black; 53% female; mean
      age, 15.7 years) from a low-to-middle class community. They completed measures of
      negative and positive emotions and attitudes, which were factor analyzed and
      yielded two factors. Positive attributes included general positive affect,
      optimistic attitudes, subjective social status, and self-esteem. Negative
      emotions included cynical attitudes, depressive symptoms, trait anger, and
      general negative affect. Components of the metabolic syndrome (waist
      circumference, glucose, blood pressure, triglycerides, and high-density
      lipoprotein cholesterol) were standardized and averaged to create a metabolic
      syndrome composite risk score. RESULTS: Linear regression analyses showed that
      the positive attributes factor was inversely associated with metabolic syndrome
      composite risk score, p < .01. The relationship remained significant after
      adjusting for age, sex, race, socioeconomic status, physical activity, smoking,
      and body mass index percentile. The negative emotion factor was unrelated to
      metabolic risk score. CONCLUSIONS: Adolescents with more positive attributes had
      lower metabolic syndrome risk scores. This study emphasizes the importance of the
      development of psychosocial resources during the adolescent transition for
      potentially reducing future cardiovascular risk.

PMID- 25060291
TI  - Enhanced spectrofluorimetric determination of esomeprazole and pantoprazole in
      dosage forms and spiked human plasma using organized media.
AB  - A simple, sensitive and rapid spectrofluorimetric method was developed for the
      determination of esomeprazole (EMZ) and pantoprazole (PRZ) in their
      pharmaceutical formulations and human plasma. The proposed method is based on the
      fluorescence spectral behavior of EMZ in methanol in the presence of 0.1 m NaOH
      containing 0.5% methyl cellulose (MC) at 306/345 nm. The fluorescence intensity
      of EMZ was enhanced about 1.3-fold and good linearity in the range 0.4-4.0 ug/mL
      with a lower detection limit of 0.04 ug/mL and lower quantification limit of 0.14
      ug/mL. For PRZ, its methanolic solution exhibited marked native fluorescence at
      290/325 nm after enhancement (about 2.1- or 1.4-fold) using either 0.025% sodium
      dodecyl sulfate (SDS) or 0.05% MC in the presence of 0.2 m borate buffer of pH
      9.5. The fluorescence-concentration plots of PRZ were rectilinear over the ranges
      0.2-2.0 and 0.3-3.0 ug/mL with lower detection limits of 0.02 and 0.03 ug/mL and
      lower quantification limits of 0.07 and 0.09 ug/mL using sodium dodecyl sulfate
      and MC, respectively. The method was successfully applied to the analysis of EMZ
      and PRZ in their commercial dosage forms and the results were in good agreement
      with those obtained with the comparison method. Furthermore, in a preliminary
      investigation, the proposed method was extended to the in vitro determination of
      the two drugs in spiked human plasma and the results were satisfactory.

PMID- 25060292
TI  - Systematic review with meta-analysis: the I148M variant of patatin-like
      phospholipase domain-containing 3 gene (PNPLA3) is significantly associated with
      alcoholic liver cirrhosis.
AB  - BACKGROUND: Several studies have reported an association between alcoholic liver
      cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic
      variant rs738409 (C>G) in adiponutrin/patatin-like phospholipase domain
      containing 3 gene (PNPLA3). AIM: To evaluate the influence of this variant on ALC
      and other forms of ALD. METHODS: We performed a systematic review of previous
      studies on the relationship between rs738409 of PNPLA3 and ALD and meta-analysis
      was conducted in a random-effects model. Calculations of the odds ratios (ORs)
      and their confidence intervals (CIs), tests for heterogeneity and sensitivity
      analyses were performed. RESULTS: Database search identified 11 previous studies
      available for inclusion with a total of 3495 patients with ALD (2087 with ALC)
      and 5038 controls (4007 healthy subjects and 1031 alcoholics without ALD).
      Patients with ALC compared to controls had a significantly higher prevalence of
      the G allele when comparing GG vs. CC (OR 4.30, 95% CI 3.25-5.69; P < 0.00001) or
      GC vs. CC genotypes (GC vs. CC: OR 1.91, 95% CI 1.67-2.17) or under a recessive
      or dominant model. Similar results were found when comparing separately patients
      with ALC vs. alcoholics without ALD or healthy subjects. An association of the G
      allele with ALD emerged when comparing ALD patients vs. alcoholics without ALD
      and/or healthy subjects although moderate to large heterogeneity was observed.
      Our data suggested an additive genetic model for this variant in ALD. CONCLUSION:
      Our meta-analysis shows that the rs738409 variant of PNPLA3 is clearly associated
      with alcoholic liver cirrhosis.

PMID- 25060294
TI  - Is diffusion-weighted MRI superior to FDG-PET or FDG-PET/CT in evaluating and
      predicting pathological response to preoperative neoadjuvant therapy in patients
      with rectal cancer?
AB  - OBJECTIVE: This meta-analysis aimed to compare the diagnostic accuracy of
      diffusion-weighted magnetic resonance imaging (DW-MRI) and fluorodeoxyglucose
      positron emission tomography (FDG-PET) or FDG-PET/computed tomography (CT) in
      evaluating and predicting pathological response to preoperative neoadjuvant
      chemoradiotherapy (NCRT) in patients with rectal cancer. METHODS: A comprehensive
      literature research was conducted to identify the relevant studies for this meta
      analysis. Combined sensitivity, specificity, positive (PPV) and negative
      predictive values (NPV) were calculated. RESULTS: A total of 33 studies including
      1564 patients met the inclusion criteria. The pooled sensitivity (81% [95% CI 74
      86%] vs 85% [95% CI 75-91%]) and NPV (80% [95% CI 68-89%] vs 91% [95% CI 80-95%])
      for FDG-PET or FDG-PET/CT were significantly lower than those for DW-MRI (P <
      0.05). No differences were observed in pooled specificity and PPV between DW-MRI
      and FDG-PET or FDG-PET/CT. Further subgroup analyses showed that DW-MRI had
      higher sensitivity on adenocarcinomas alone than on those including mucinous-type
      adenocarcinomas (92% [95% CI 83-99%] vs 76% [95% CI 63-90%], P = 0.00).
      CONCLUSIONS: DW-MRI is superior to FDG-PET or FDG-PET/CT in predicting and
      evaluating pathological responses to preoperative NCRT in patients with rectal
      cancer. However, its relatively low specificity and PPV limit its application in
      clinic, making it currently inappropriate to monitor such patients, especially
      those with mucinous-type rectal adenocarcinomas.

PMID- 25060295
TI  - Periostin and receptor activator of nuclear factor kappa-B ligand expression in
      allergic fungal rhinosinusitis.
AB  - BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a disease demonstrating
      substantial eosinophilic inflammation and characteristic radiographic bony
      erosion/expansion. Periostin is an extracellular matrix protein associated with
      eosinophil accumulation in eosinophilic esophagitis, allergic asthma mucus
      production, and chronic rhinosinusitis (CRS) polyp formation. Receptor activator
      of nuclear factor kappa-B ligand (RANKL) is an osteoclast activator present in
      osteoporosis and periodontal disease. We sought to evaluate periostin and RANKL
      expression in AFRS and correlate these levels with radiographic scales of disease
      severity. METHODS: Thirty sinus tissue specimens were intraoperatively collected
      from 3 patient groups: AFRS; CRS without nasal polyps (CRSsNP); and controls (n =
      10 per group). Specimens were analyzed by semiquantitative reverse-transcription
      polymerase chain reaction (sq-RT-PCR) and immunofluorescence (IF)
      labeling/confocal microscopy for the presence of both periostin and RANKL.
      Immunofluorescence staining intensity was quantified by pixel density analysis.
      Preoperative computed tomography (CT) scans from each patient were scored using
      both the Lund-Mackay and CT bone erosion scoring systems. RESULTS: Periostin was
      significantly elevated in AFRS sinus tissue compared to CRSsNP and controls, as
      demonstrated by IF (p < 0.001) and PCR (p = 0.011). RANKL was not detected in
      sinus tissue by IF or PCR. Periostin levels positively correlated with
      radiographic indices of disease severity for both soft tissue and bone, using
      Lund-Mackay (r = 0.926 [PCR] and r = 0.581 [IF]) and CT bone erosion (r = 0.672
      [PCR] and r = 0.616 [IF]) scoring systems, respectively. CONCLUSION: Periostin is
      increased in AFRS tissue compared to CRSsNP and controls. Periostin levels
      positively correlate with radiologic disease severity scores. The increased
      levels of periostin in AFRS are possibly tied to its intense eosinophilic
      inflammatory etiology.

PMID- 25060296
TI  - [Assessment of environmental contamination of drinking water. Recommendation of
      the Federal Environment Agency (UBA) after consultation with the Drinking Water
      Commission of the Federal Ministry of Health (BMG) Federal Environment
      Agency.burtiger].

PMID- 25060297
TI  - [Identification and assessment of chemical contamination of the air of indoor
      work places (without activity involving hazardous substances). Joint Press
      Release by the working group air analysis of the Permanent Commission for the
      Investigation of Health Hazards of Chemical Compounds in the research community
      and the ad hoc working group indoor indicative of the Commission's Indoor Air
      Hygiene and the Supreme Health Authorities].

PMID- 25060293
TI  - Epigenetic pathway targets for the treatment of disease: accelerating progress in
      the development of pharmacological tools: IUPHAR Review 11.
AB  - The properties of a cell are determined both genetically by the DNA sequence of
      its genes and epigenetically through processes that regulate the pattern, timing
      and magnitude of expression of its genes. While the genetic basis of disease has
      been a topic of intense study for decades, recent years have seen a dramatic
      increase in the understanding of epigenetic regulatory mechanisms and a growing
      appreciation that epigenetic misregulation makes a significant contribution to
      human disease. Several large protein families have been identified that act in
      different ways to control the expression of genes through epigenetic mechanisms.
      Many of these protein families are finally proving tractable for the development
      of small molecules that modulate their function and represent new target classes
      for drug discovery. Here, we provide an overview of some of the key epigenetic
      regulatory proteins and discuss progress towards the development of
      pharmacological tools for use in research and therapy.

PMID- 25060298
TI  - Translational challenges in targeting latent HIV infection and the CNS reservoir
      problem.
AB  - Too controversial to discuss only a short time ago, achieving a cure for HIV
      infection has become a priority in HIV research. However, substantial challenges
      must be overcome. Among key hurdles to be surmounted is the definition of a
      reliable, validated model in which to test latency reversal agents (LRAs), as
      current primary cell models differ in their response to such agents. Animal
      models such as the HIV-infected humanized BLT mouse and SIV-infected macaque will
      be essential to study LRAs and to quantify their effects in anatomic reservoirs.
      Of several potential anatomic reservoirs, the central nervous system presents a
      significant obstacle, as it is known to harbor persistent HIV infection and is
      difficult to access for study and therapeutic intervention. 

PMID- 25060299
TI  - Evidence for cFMS signaling in HIV production by brain macrophages and microglia.
AB  - Combination antiretroviral therapy (cART) has improved the longevity and quality
      of life for people living with HIV; however, it does not target virus that
      persists in long-lived cells, such as macrophages (MPhis). This allows for the
      development of viral reservoirs in various anatomical compartments where these
      cells reside, including the central nervous system (CNS), where perivascular
      MPhis and resident microglia constitute the principle cellular reservoir of HIV.
      How HIV persists in MPhis/microglia is not completely understood; however,
      prosurvival signaling that protects infected MPhis/microglia from apoptosis is
      likely important to viral persistence. Macrophage colony-stimulating factor (M
      CSF) is an important factor in MPhi survival and has been implicated in HIV
      neuropathogenesis through its ability to enhance the susceptibility of MPhis to
      infection and promote virus production. While M-CSF has been detected in
      cerebrospinal fluid of HIV-infected patients, the cellular source of M-CSF in the
      CNS is unknown. Here, we demonstrate, for the first time, that MPhis comprising
      perivascular cuffs and nodular lesions in SIV encephalitis (SIVE) brain are the
      principle source of M-CSF. These cells also serve as the primary reservoir of
      productive SIV infection in the brain. We further demonstrate that M-CSF and IL
      34, which signal through the same receptor, cFMS, enhance HIV-1 production by
      microglia in vitro. This is attenuated by the addition of a receptor tyrosine
      kinase inhibitor with high specificity for cFMS, GW2580. Together, these data
      suggest that cFMS signaling may be an attractive target for eliminating long
      lived MPhi reservoirs of HIV in the brain and other tissues. 

PMID- 25060301
TI  - Venous uptake despite negative aspiration during fluoroscopically guided
      interlaminar cervical epidural steroid injections.

PMID- 25060300
TI  - HIV-1 transcriptional regulation in the central nervous system and implications
      for HIV cure research.
AB  - Human immunodeficiency virus type-1 (HIV-1) invades the central nervous system
      (CNS) during acute infection which can result in HIV-associated neurocognitive
      disorders in up to 50% of patients, even in the presence of combination
      antiretroviral therapy (cART). Within the CNS, productive HIV-1 infection occurs
      in the perivascular macrophages and microglia. Astrocytes also become infected,
      although their infection is restricted and does not give rise to new viral
      particles. The major barrier to the elimination of HIV-1 is the establishment of
      viral reservoirs in different anatomical sites throughout the body and viral
      persistence during long-term treatment with cART. While the predominant viral
      reservoir is believed to be resting CD4(+) T cells in the blood, other anatomical
      compartments including the CNS, gut-associated lymphoid tissue, bone marrow, and
      genital tract can also harbour persistently infected cellular reservoirs of HIV
      1. Viral latency is predominantly responsible for HIV-1 persistence and is most
      likely governed at the transcriptional level. Current clinical trials are testing
      transcriptional activators, in the background of cART, in an attempt to purge
      these viral reservoirs and reverse viral latency. These strategies aim to
      activate viral transcription in cells constituting the viral reservoir, so they
      can be recognised and cleared by the immune system, while new rounds of infection
      are blocked by co-administration of cART. The CNS has several unique
      characteristics that may result in differences in viral transcription and in the
      way latency is established. These include CNS-specific cell types, different
      transcription factors, altered immune surveillance, and reduced antiretroviral
      drug bioavailability. A comprehensive understanding of viral transcription and
      latency in the CNS is required in order to determine treatment outcomes when
      using transcriptional activators within the CNS.

PMID- 25060302
TI  - Female athletes: a population at risk of vitamin and mineral deficiencies
      affecting health and performance.
AB  - Adequate vitamin and mineral status is essential for optimal human health and
      performance. Female athletes could be at risk for vitamin and mineral
      insufficiency due to inadequate dietary intake, menstruation, and inflammatory
      responses to heavy physical activity. Recent studies have documented poor iron
      status and associated declines in both cognitive and physical performance in
      female athletes. Similarly, insufficient vitamin D and calcium status have been
      observed in female athletes, and may be associated with injuries, such as stress
      fracture, which may limit a female athlete's ability to participate in regular
      physical activity. This review will focus on recent studies detailing the
      prevalence of poor vitamin and mineral status in female athletes, using iron,
      vitamin D, and calcium as examples. Factors affecting the dietary requirement for
      these vitamins and minerals during physical training will be reviewed. Lastly,
      countermeasures for the prevention of inadequate vitamin and mineral status will
      be described. 

PMID- 25060303
TI  - Manganese pre-treatment attenuates cadmium induced hepatotoxicity in Swiss albino
      mice.
AB  - Cadmium (Cd) is a soft, malleable bluish-white metal with low melting point, a
      ubiquitous heavy metal and an environmental pollutant, found in soil, water and
      air. The presence of Cd in the components of the environment such as air, soil
      and groundwater is to a large part due to human activity, and the general
      population is exposed mainly by contaminated drinking water or food. Manganese
      (Mn) is a component in many enzymes, which play an important role in
      counteracting oxidative stress. In vitro experiments have revealed the ability of
      Mn to scavenge oxygen free radicals generated in differently mediated lipid
      peroxidation (LPO) conditions. The aim of the present study was to investigate
      the in vivo preventive effect of Mn(2+) pre-treatment on acute Cd-intoxication
      with regard to oxidative stress biomarker and antioxidant defense system in liver
      of Swiss albino mice. On exposure to Cd a significant increase in LPO levels,
      decrease in thiol content and induction in glutathione metabolizing enzyme were
      observed. Mn pre-treatment attenuated the modulation caused in the above
      mentioned parameters due to acute Cd exposure in mice. In conclusion, the results
      from this study demonstrate that the protective effect of Mn in Cd-induced
      systemic toxicity in mice. Further investigations are required on the relation
      between Mn accumulation and resistance to oxidative stress and on the factors
      influencing Mn/Cd transport in rodents are needed to elucidate the molecular
      basis of this protective effect. 

PMID- 25060304
TI  - First line and salvage therapy with total therapy 3-based treatment for multiple
      myeloma- an extended single center experience.
AB  - Total therapy 3 is an intensified protocol for multiple myeloma (MM). The "real
      life" outcomes of this protocol were seldom reported. Data was obtained for 81
      patients (newly diagnosed, n=49; progressive MM, n=32), most of which had high
      risk parameters. Overall response rate following (V)DT-PACE was 96% and 75% for
      the newly diagnosed and progressive groups, respectively. Median progression-free
      survival was 42.5 and 9 months, respectively. The 2-year overall survival was 88%
      and 40%, respectively. Treatment with (V)DT-PACE achieves high response rate
      among patients with high-risk disease, which can be translated into long-term
      remission only for newly diagnosed patients. 

PMID- 25060305
TI  - C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic
      significance?
AB  - C-myc protein expression has been studied in mature B-cell lymphomas and
      overexpression has been associated with poor prognosis. We sought to determine
      the prognostic significance of c-myc protein expression in B-ALL. We found >= 20%
      c-myc expression to predict risk of persistent disease in all age groups (odds
      ratio 7.487, p=0.013). There was no statistically significant association between
      c-myc expression and risk of relapse or death in our study. Routine c-myc
      immunostaining may help identify higher risk patients and guide management of B
      ALL. Additional studies are needed to further determine the molecular mechanisms
      and role of c-myc expression in B-ALL.

PMID- 25060306
TI  - Efficacy and tolerability of a high loading dose (25,000 IU weekly) vitamin D3
      supplementation in obese children with vitamin D insufficiency/deficiency.
AB  - BACKGROUND: The recommended dose of vitamin D supplementation of 400 IU/day might
      be inadequate to treat obese children with vitamin D insufficiency. Therefore, we
      tested the efficacy and tolerability of a high loading dose vitamin D3
      supplementation of 25,000 IU weekly in multiethnic obese children, 8-18 years of
      age, with vitamin D insufficiency/deficiency. METHODS: Fasting blood samples were
      drawn for the assessment of vitamin D. Vitamin D-insufficient/-deficient children
      (<50 nmol/l) were supplemented, using a high loading dose of 25,000 IU weekly,
      and measured again 9 weeks later. Vitamin D supplementation was considered
      effective and tolerable when an increase to vitamin D sufficiency (25(OH)D >50
      nmol/l) was reached in >75% without side effects nor reaching toxic levels.
      RESULTS: In total, 109 children (mean +/- SD age 11.1 +/- 3.0, 34.2% boys, 90.8%
      obese) received vitamin D supplementation. In 84.4% of the children, the vitamin
      D status improved from insufficiency/deficiency (<50 nmol/l) to sufficiency (>=50
      nmol/l). The majority of children that did not reach vitamin D sufficiency
      reported non-compliance. No side effects were reported, and the highest level
      reached was far below the threshold for toxicity. CONCLUSION: A high loading dose
      vitamin D3 supplementation is effective and well-tolerated in our cohort of
      multiethnic obese children with vitamin D insufficiency/deficiency.

PMID- 25060307
TI  - Genetic similarities between tobacco use disorder and related comorbidities: an
      exploratory study.
AB  - BACKGROUND: Tobacco use disorder (TUD), defined as the use of tobacco to the
      detriment of a person's health or social functioning, is associated with various
      disorders. We hypothesized that mutual variation in genes may partly explain this
      link. The aims of this study were to make a non-exhaustive inventory of the
      disorders using (partially) the same genetic pathways as TUD, and to describe the
      genetic similarities between TUD and the selected disorders. METHODS: We
      developed a 3 stage approach: (i) selection of genes influencing TUD using
      Gene2Mesh and Ingenuity Pathway Analysis (IPA), (ii) selection of disorders
      associated with the selected genes using IPA and (iii) genetic similarities
      between disorders associated with TUD using Jaccard distance and cluster
      analyses. RESULTS: Fourteen disorders and thirty-two genes met our inclusion
      criteria. The Jaccard distance between pairs of disorders ranged from 0.00 (e.g.
      oesophageal cancer and malignant hypertension) to 0.45 (e.g. bladder cancer and
      addiction). A lower number in the Jaccard distance indicates a higher similarity
      between the two disorders. Two main clusters of genetically similar disorders
      were observed, one including coexisting disorders (e.g. addiction and alcoholism)
      and the other one with the side-effects of smoking (e.g. gastric cancer and
      malignant hypertension). CONCLUSIONS: This exploratory study partly explains the
      potential genetic components linking TUD to other disorders. Two principle
      clusters of disorders were observed (i) coexisting disorders of TUD and (ii) side
      effects of TUD disorders. A further deepening of this observation in a real life
      study should allow strengthening this hypothesis.

PMID- 25060308
TI  - Immobilization of Pb, Cd, and Zn in a contaminated soil using eggshell and banana
      stem amendments: metal leachability and a sequential extraction study.
AB  - Heavy-metal-contaminated soil is one of the major environmental pollution issues
      all over the world. In this study, two low-cost amendments, inorganic eggshell
      and organic banana stem, were applied to slightly alkaline soil for the purpose
      of in situ immobilization of Pb, Cd, and Zn. The artificially metal-contaminated
      soil was treated with 5% eggshell or 10% banana stem. To simulate the rainfall
      conditions, a metal leaching experiment for a period of 12 weeks was designed,
      and the total concentrations of the metals in the leachates were determined every
      2 weeks. The results from the metal leaching analysis revealed that eggshell
      amendment generally reduced the concentrations of Pb, Cd, and Zn in the
      leachates, whereas banana stem amendment was effective only on the reduction of
      Cd concentration in the leachates. A sequential extraction analysis was carried
      out at the end of the experiment to find out the speciation of the heavy metals
      in the amended soils. Eggshell amendment notably decreased mobility of Pb, Cd,
      and Zn in the soil by transforming their readily available forms to less
      accessible fractions. Banana stem amendment also reduced exchangeable form of Cd
      and increased its residual form in the soil.

PMID- 25060309
TI  - Hydrochemistry dynamics in remote mountain lakes and its relation to catchment
      and atmospheric features: the case study of Sabocos Tarn, Pyrenees.
AB  - Increasing the understanding of high mountain lake dynamics is essential to use
      these remote aquatic ecosystems as proxies of global environmental changes. With
      this aim, at Sabocos, a Pyrenean cirque glacial lake or tarn, this study shows
      the main results of a morphological and catchment characterization, along with
      statistical analyses of its hydrochemical trends and their concomitant driving
      factors from 2010 to 2013. Dissolved oxygen, water temperature stratification,
      and its snow and ice cover composition and dynamics have been also investigated.
      According to morphological analyses, Sabocos can be classified as a medium-large
      and deep lake, having a circular contour and a long water retention time as
      compared to Pyrenean glacial lake average values. Sabocos hydrochemistry is
      mainly determined by very high alkalinity, pH and conductivity levels, and high
      Ca(2+), Mg(2+), and SO4(2-) content, coming from the easily weatherable limestone
      dolomite bedrock. Thus, lake water is well buffered, and therefore, Sabocos tarn
      is non-sensitive to acidification processes. On the other hand, the main source
      of K(+), Na(+), and Cl(-) (sea salts) and nutrients (NH4(+), NO3(-), and
      phosphorous) to lake water appears to be atmospheric deposition. Primary
      production is phosphorous limited, and due to the N-saturation stage of the
      poorly developed soils of Sabocos catchment, NO3(-) is the chief component in the
      total nitrogen pool. External temperature seems to be the major driver regulating
      lake productivity, since warm temperatures boot primary production. Although
      precipitation might also play an important role in lake dynamics, especially
      regarding to those parameters influenced by the weathering of the bedrock, its
      influence cannot be easily assessed due to the seasonal isolation produced by the
      ice cover. Also, as occurs in the whole Pyrenean lake district, chemical
      composition of bulk deposition is highly variable due to the contribution of air
      masses with different origin.

PMID- 25060311
TI  - Methods for assessing the energy-saving efficiency of industrial symbiosis in
      industrial parks.
AB  - The available energy resources are being depleted worldwide. Industrial symbiosis
      (IS) provides a promising approach for increasing the efficiency of energy
      utilization, with numerous studies reporting the superiority of this technology.
      However, studies quantifying the energy-saving efficiency of IS remain
      insufficient. This paper proposes an index system for the quantitative evaluation
      of the energy-saving efficiency of IS. Both energy-saving and financial indexes
      were selected, the former include the IS energy-saving index, the contribution
      rate of energy saved through IS, fractional energy savings, and cut rate of
      energy consumption per total output value; and the latter include the IS
      investment payback period, IS input-output ratio, net present value (NPV), and
      internal rate of return (IRR) of IS. The proposed methods were applied to a case
      study on the XF Industrial Park (XF IP), in the city of Liaocheng in Shandong
      Province of China. Three energy-saving channels using IS were found in the XF IP:
      (a) utilizing the energy of high-temperature materials among industrial
      processes, (b) recovering waste heat and steam between different processes, and
      (c) saving energy by sharing infrastructures. The results showed that the energy
      efficiency index of IS was 0.326, accounting for 34.6% of the comprehensive
      energy-saving index in 2011, and the fractional energy-savings were 12.42%. The
      index of energy consumption per total industrial output value varied from 90.9
      tce/MRMB to 51.6 tce/MRMB. Thus, the cut rate of energy consumption per total
      industrial output value was 43.42%. The average values of the IS input-output
      ratio was 406.2 RMB/tce, 57.2% lower than the price of standard coal. Static
      investment payback period in the XF IP was 8.5 months, indicating that the XF IP
      began to earn profit 8.5 months after the construction of all IS modes. The NVP
      and IRR of each IS mode in the XF IP were greater than zero, with average values
      equal to 1,789.96 MRMB and 140.96%, respectively. The computation result for each
      indicator revealed that IS could lead to the use of energy with high efficiency
      and lighten the financial burden of enterprises in the XF IP. And the proposed
      index system may help IPs and EIPs to make strategic decisions when designing IS
      modes.

PMID- 25060310
TI  - Role of AHR, AHRR and ARNT in response to dioxin-like PCBs in Spaurus aurata.
AB  - The aryl hydrocarbon receptor (AHR) mediates a variety of biological responses to
      ubiquitous dioxin and PCB dioxin-like. AHR together with ARNT, AHRR, represent a
      novel basic helix-loop-helix/PAS family of transcriptional regulators. Their
      interplay may affect the xenobiotic response. The aim of this study was to
      investigate, by histological, immunohistochemical investigations and western-blot
      analysis, the expression of AHR, ARNT and AHRR in liver of seabrem (Spaurus
      aurata) after exposure at different time to dioxin-like PCB126 in order to deep
      the knowledge about their specific role. The findings showed a significant
      increase of AHR and ARNT expression in juvenile fishes after 12 h than control
      group. The induction of AHR and ARNT is also significant at 24 and 72 hours
      compared to the control group. Furthemore, induction of AHRR expression has
      proved to increase both 12 h but this induction does not seem significant to 24
      and 72 hours. The most important data of this work is that the induction of AHRR,
      when the action of the toxic persistence substances, as dioxin and PCB-126, it is
      not enough to reduce AHR signaling and thus its hyperactivation leads to toxic
      effects in seabrem (Spaurus aurata). All this confirms the importance of AHR
      ligands as new class of drugs that can be directed against severe disease such as
      cancer.

PMID- 25060312
TI  - Life cycle analysis of management options for organic waste collected in an urban
      area.
AB  - Different options for managing the organic fraction (OF) of municipal solid waste
      generated in a given urban area were analyzed by life cycle assessment (LCA) for
      different source segregation (SS) intensities ranging from 0 to 52%. The best
      management option for processing the OF remaining in the residual organic
      fraction (ROF) for the different SS intensities was by incineration. Landfilling
      and mechanical biological treatment (MBT) of ROF gave higher impacts. Aerobic
      treatment alone or combined with anaerobic digestion (AD) for processing the
      source-segregated organic fraction (SSOF) led to relevant environmental impact
      reduction even if the difference between the two options was quite negligible.
      The weighted impact showed that scenarios using incineration always gave
      environmental gains, whereas there was a higher environmental burden with the
      scenarios using MBT.

PMID- 25060313
TI  - Soil heavy metal dynamics and risk assessment under long-term land use and
      cultivation conversion.
AB  - Long-term agricultural development and cultivation conversions affect soil heavy
      metal balance and the regional environmental safety. In this study, heavy metal
      parameters were used to identify changes in soil properties in response to land
      use and cultivation conversions. The integrated soil quality index, which
      involves seven heavy metal indices, was proposed to assess the environmental risk
      of long-term human activities in Northeast China. We used the remote sensing and
      geographical data for the four-term land use distribution from 1979 to 2009 to
      identify the spatial patterns of regional land use conversions. Then, 41 samples
      from the top 20 cm of the soil at sites corresponding to these seven types of
      conversions were collected (permanent dry land, dry land converted from wetland,
      dry land converted from forest, permanent wetland, permanent forest, paddy land
      converted from dry land, and paddy land converted from wetland). Based on the
      local soil properties and tillage practices, the following seven heavy metal
      parameters were employed: Arsenic (As), Cadmium (Cd), Chromium (Cr), Copper (Cu),
      Nickel (Ni), Lead (Pb), and Zinc (Zn). The conversion of farmland from wetland
      resulted in an increase in the concentration of Pb and Cr in the soil. In
      contrast, the concentrations of Zn, Cu, Ni, and Cd decreased when wetland was
      converted into farmland because the tillage practices washed these heavy metals
      away. During the conversion of dry land and paddy land to wetland, the levels of
      Pb increased by approximately 28.6% and 24.7%, respectively. Under the same
      conditions, the concentration of As increased by 32.5% and 14.1%, respectively.
      The integrated index also demonstrated that the farmlands were not contaminated
      by the heavy metals during long-term agricultural development.

PMID- 25060314
TI  - Synthesis of mesoporous Mn/TiO2 nanocomposites and investigating the
      photocatalytic properties in aqueous systems.
AB  - Mesoporous 20 wt% Mn/TiO2 nanocomposites were synthesized adopting modified sol
      gel method at different pH (pH = 2, 7 and 11) conditions and calcined at 400 
      degrees C. Based on the characteristics of the 20 wt% Mn/TiO2 nanocomposites
      synthesized at pH 11, same procedure was adopted for the synthesis of different
      wt% Mn/TiO2. The nanocomposite samples and their surface properties were
      characterized by X-ray powder diffraction (XRD), scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), high resolution transmission
      electron microscopy (HRTEM), mapping, inductively coupled plasma optical emission
      spectrometry (ICP-OES), Fourier transform infrared (FTIR), and fluorescence
      spectrometry. The nanocomposites existed in the anatase phase of TiO2 with no
      peak assigned to Mn on the diffractogram. The photocatalytic activities of the
      materials were evaluated by monitoring degradation of a model dye (methylene blue
      (MB)) in presence of visible light and ozone. The nanocomposite synthesized under
      neutral condition (pH = 7) exhibited the best photocatalytic activity resulting
      from its relatively smaller crystal size (5.98 nm) and larger pore volume (0.30
      cm(3)/g). One percentage of weight Mn/TiO2 showed 100% decolouration of MB in the
      presence of O3 after 100 min.

PMID- 25060315
TI  - Caregiving frequency and physical function: the Women's Health Initiative.
AB  - BACKGROUND: Informal caregiving is common for older women and can negatively
      affect health, but its impact on physical function remains unclear. Using inverse
      probability weighting methods, we quantified the association of caregiving with
      physical function over 6 years. METHODS: Study participants were 5,649 women aged
      65 years and older at baseline of the Woman's Health Initiative Clinical Trial
      (multicenter recruitment, 1993-1998) with complete caregiving data and function
      at baseline and at least one follow-up. Caregiving was self-reported (low
      frequency if <=2 times per week and high-frequency if >=3 times per week).
      Performance-based measures of physical function including timed walk
      (meters/second), grip strength (kilograms), and chair stands (number) were
      measured at baseline and years 1, 3, and 6. Associations and 95% confidence
      intervals of baseline caregiving with physical function were estimated by
      generalized estimating equations with inverse probability weighting by propensity
      and attrition scores, calculated by logistic regression of baseline health and
      demographic characteristics. RESULTS: Over follow-up, low-frequency caregivers
      had higher grip strength when compared with noncaregivers (mean difference =
      0.63kg, confidence interval: 0.24, 1.01). There were no observed differences
      between high-frequency caregivers and noncaregivers on grip strength or for
      either caregiver group when compared with noncaregivers on walk speed or chair
      stands. Rates of change in physical function measures did not differ by
      caregiving status. CONCLUSIONS: Caregiving was not associated with poorer
      physical function in this sample of older women. Low-frequency caregiving was
      associated with better grip strength at baseline which persisted through follow
      up. This study supports the concept that informal caregiving may not have
      universally negative health consequences.

PMID- 25060316
TI  - Comorbidity and functional trajectories from midlife to old age: the Health and
      Retirement Study.
AB  - BACKGROUND: The number of diseases and physical functioning difficulties tend to
      increase with age. The aim of this study was to examine the trajectories of
      physical functioning across age groups and whether the trajectories differ
      according to disease status in different population subgroups. METHODS: Repeat
      data from a nationally representative population sample, the Health and
      Retirement Study, was used. Participants were 10,709 men and 13,477 women aged 60
      107 years at baseline with biennial surveys from 1992 to 2010. Average length of
      follow-up was 10.3 years ranging from 0 to 18 years. Disease status and physical
      functioning was asked about at all study phases and 10 items were summed to
      obtain a physical functioning score (0-10). RESULTS: Age modified the
      relationship between number of chronic diseases and physical functioning with
      older participants having more physical functioning difficulties with increasing
      number of diseases. An average 70-year-old participant with no diseases had 0.89
      (95% CI: 0.85-0.93) physical functioning difficulties, with one disease 1.72 (95%
      CI: 1.69-1.76) difficulties, with two diseases 2.57 (95% CI: 2.52-2.62)
      difficulties, and with three or more diseases 3.82 (95% CI: 3.76-3.88)
      difficulties. Of the individual diseases memory-related diseases, stroke,
      pulmonary diseases, and arthritis were associated with significantly higher
      physical functioning difficulties compared with other diseases. CONCLUSIONS:
      Comorbidity is associated with greater burden of physical functioning
      difficulties. Of the studied diseases, memory-related diseases, stroke, pulmonary
      diseases, and arthritis alone or in combination limit most physical functioning.

PMID- 25060318
TI  - Adhesive attachments of the endangered botfly, Portschinskia magnifica (Diptera:
      Oestridae).
AB  - Portschinskia magnifica (Diptera: Oestridae) is an endangered subcutaneous
      parasitic fly that is mainly distributed in Eurasia. The external morphology of
      the main adhesive attachments that include the pretarsus and tarsus is studied
      using scanning electron microscopy. Two types of tenent setae that are
      characterised as spoon-like tip and pointed-like tip, which can increase the
      contact points for attachment to a surface, are described in this study. Hairs
      around the bristle of the empodium in P. magnifica are much denser than those of
      other flies, and thus, we proposed that the dense hairs around the empodium may
      be a more efficient way to perform the sensory function. Compared with
      saprophagous flies that are reported previously, the microsculpture of the
      unguitractor plate is obviously different in that microplates are scale-like and
      similar to those of the water bug, Ranatra linearis. In addition, microtrichia
      found in the lateral region of the unguitractor plate provides stronger fixation
      between two surfaces. These results provide anatomical information that allows us
      to understand the role of the pretarsus as an attachment device. 

PMID- 25060317
TI  - An identification key for the five most common species of Metastrongylus.
AB  - Species of the Metastrongylus genus, the lung nematodes of pigs that require an
      intermediate host (earthworm) to complete their cycle, pose a potential risk to
      both livestock and humans. This parasite which can result in lung pathology and
      mixed infections with other pathogens (e.g. viruses) can be fatal to pigs.
      Although this genus is distributed worldwide, there are no classification keys
      for identifying this common parasite species. In this work, we take advantage of
      parasitological surveys of wild boar (Sus scrofa) in northern and central Spain
      and southern Poland to develop a morphological identification key for the five
      most common Metastrongylus species (Metastrongylus apri, Metastrongylus
      pudendotectus, Metastrongylus salmi, Metastrongylus confusus and Metastrongylus
      asymetricus). In addition, we provide the first record of M. confusus in Spain,
      probably unidentified until now due to the lack of appropriate identification
      keys. We hope that this user-friendly identification key will enable
      parasitologists and veterinary practitioners to avoid further misclassifications
      of Metastrongylus species. 

PMID- 25060319
TI  - Trigeminal-hypoglossal silent period: a pontomedullary brainstem reflex.
AB  - INTRODUCTION: Animal studies have shown inhibitory connections between the
      sensory trigeminal nucleus and hypoglossal nucleus. I investigated whether these
      inhibitory projections are present in humans. METHODS: I examined 18 healthy
      subjects, 2 patients with brainstem stroke, and 5 patients with multiple
      sclerosis using a specially designed oral stimulation and recording device.
      RESULTS: In 16 of 18 subjects, a bilateral suppression period of tongue muscle
      activity after unilateral electrical stimulation of the mucosal V2 afferents was
      observed. The silent period started at 31.1 (SD 4.7) ms (ipsilateral) and 32.0
      (SD 4.9) ms (contralateral). The mean duration of the silent period was 31.4 (SD
      10.2) ms (ispilateral) and 32.5 (SD 9.8) ms (contralateral). Patients with
      dorsolateral pontomedullary lesions had ipsilateral absence of the silent period.
      CONCLUSIONS: This study confirms the existence of a bilateral trigeminal
      hypoglossal silent period in humans.

PMID- 25060320
TI  - Epigenetic regulation of adult stem cell function.
AB  - Understanding the cellular and molecular mechanisms that specify cell lineages
      throughout development, and that maintain tissue homeostasis during adulthood, is
      paramount towards our understanding of why we age or develop pathologies such as
      cancer. Epigenetic mechanisms ensure that genetically identical cells acquire
      different fates during embryonic development and are therefore essential for the
      proper progression of development. How they do so is still a matter of intense
      investigation, but there is sufficient evidence indicating that they act in a
      concerted manner with inductive signals and tissue-specific transcription factors
      to promote and stabilize fate changes along the three germ layers during
      development. In consequence, it is generally hypothesized that epigenetic
      mechanisms are also required for the continuous maintenance of cell fate during
      adulthood. However, in vivo models in which different epigenetic factors have
      been depleted in different tissues do not show overt changes in cell lineage,
      thus not strongly supporting this view. Instead, the function of some of these
      factors appears to be primarily associated with tissue functionality, and a
      strong causal relationship has been established between their misregulation and a
      diseased state. In this review, we summarize our current knowledge of the role of
      epigenetic factors in adult stem cell function and tissue homeostasis.

PMID- 25060321
TI  - Actinic keratosis: new concepts and therapeutic approaches for an ancestral
      condition.

PMID- 25060322
TI  - Lymph node micrometastases is a poor prognostic factor for patients in pN0
      gastric cancer: a meta-analysis of observational studies.
AB  - BACKGROUND: There is no consensus as to the impact of lymph node micrometastases
      (LNMM) on survival of patients with gastric cancer. The aim of this analysis was
      to investigate the prognostic significance of LNMM in patients with histologic
      node-negative gastric cancer. METHODS: We searched relevant studies from PubMed,
      Embase, and the Cochrane Library (1966-2013.5), used software STATA 12.0 to pool
      the outcomes of each study. Mantel-Haenszel and Inverse Variance methods were
      used in a fixed effect model and a random effect model, respectively. The hazard
      ratios (HR) and odds risk (OR) at their 95% confidence intervals (CIs) were used
      as measures to investigate the prognostic importance of LNMM, by searching for a
      correlation between the clinical pathologic features and LNMM. RESULTS: Our
      analysis of 18 eligible studies revealed that patients with LNMM had an increased
      likelihood of having a worse 5-y survival rate (HR 2.81; 95% CI: 1.96-4.02).
      Subgroup analyses showed a more significant result for patients in pT1-2N0 (HR
      3.52; 95% CI 1.88-6.62). The analyses also revealed that (OR 1.32; 95% CI 1.17
      1.48), lymphatic invasion (OR 2.21; 95% CI 1.42-3.44) and venous invasion (OR
      1.41; 95% CI 1.08-1.85) were associated with the occurrence of LNMM. CONCLUSIONS:
      There is a positive correlation between LNMM and an unfavorable surgical outcome
      in gastric cancer. Undifferentiated histologic findings, lymphatic invasion, and
      venous invasion are high risk factors for the occurrence of LNMM.

PMID- 25060323
TI  - Sonographic assessment of renal size in healthy adults.
AB  - OBJECTIVE: To assess the normal sonographic values of renal length and cortical
      thickness in healthy adults and establish reference ranges in our population for
      comparison when examining renal disease. SUBJECTS AND METHODS: Sonographic
      assessment of renal length and cortical thickness were performed from January
      2006 to December 2011 in 252 healthy individuals who were self-referred to the El
      Reshaid Renal Clinic in Kuwait. They were screened for the absence of renal
      abnormalities. Weight and height were measured, and body mass index (BMI) and
      body surface area calculated. Patients were divided into 5 age groups: 18-30, 31
      40, 41-50, 51-60 and 61-80 years, in order to generate reference graphs for renal
      length and cortical thickness. RESULTS: The mean renal lengths for the right and
      left kidney were 10.68 +/- 1.4 and 10.71 +/- 1.0 cm, respectively (p = 0.56)
      without a significant change with age. The minimum cortical thickness was 0.6 cm.
      The renal length correlated with the weight of the patients (p < 0.01) and their
      BMI (p < 0.01) but not with their height. There was no difference in renal size
      or cortical thickness in patients older than 60 years despite an age-related
      decline in the glomerular filtration rate (p < 0.001). CONCLUSIONS: Renal length
      and cortical thickness did not vary significantly with age. Renal length
      correlated well with weight and BMI but not with height. Hence, establishing
      normal ranges of renal parameters is essential for comparison in situations where
      possible renal disease is being investigated.

PMID- 25060324
TI  - SEUSS and SEUSS-LIKE 2 coordinate auxin distribution and KNOXI activity during
      embryogenesis.
AB  - In Arabidopsis, SEUSS (SEU) and SEUSS-LIKE 2 (SLK2) are components of the LEUNIG
      (LUG) repressor complex that coordinates various aspects of post-embryonic
      development. The complex also plays a critical role during embryogenesis, as seu
      slk2 double mutants have small, narrow cotyledons and lack a shoot apical
      meristem (SAM). Here we show that seu slk2 double mutant embryos exhibit delayed
      cotyledon outgrowth and that this is associated with altered PIN-FORMED1 (PIN1)
      expression and localisation during the early stages of embryogenesis. These
      observations suggest that SEU and SLK2 promote the transition to bilateral
      symmetry by modulating auxin distribution in the embryonic shoot. This study also
      shows that loss of SAM formation in seu slk2 mutants is associated with reduced
      expression of the class I KNOX (KNOXI) genes SHOOTMERISTEMLESS (STM),
      BREVIPEDICELLUS and KNAT2. Furthermore, elevating STM expression in seu slk2
      mutant embryos was sufficient to restore SAM formation but not post-embryonic
      activity, while both SAM formation and activity were rescued when SLK2 expression
      was restored in either the cotyledons or boundary regions. These results
      demonstrate that SEU and SLK2 function redundantly to promote embryonic shoot
      development and likely act through a non-cell autonomous pathway to promote KNOXI
      activity. 

PMID- 25060326
TI  - Targeting under-diagnosis in hereditary hemorrhagic telangiectasia: a model
      approach for rare diseases?
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal
      dominant disease, is considered under-diagnosed. Our primary objective was to
      provide evidence of under-diagnosis of HHT in a North American population. We
      hypothesized that variation would exist in the diagnosed prevalence (D
      prevalence) across regions in the province of Ontario, Canada and across age
      groups, due to under-diagnosis in certain groups. Our secondary objective was to
      collect data regarding contact and local access to consult specialists by HHT
      patients to help guide potential future diagnostic programs. METHODS: Primary
      objective- 556 adult patients with a definite HHT diagnosis seen at the Toronto
      HHT Centre were identified and geocoded with postal codes. Prevalence rates were
      calculated using Canadian census data. Secondary objective- A driving network
      model was developed in ArcGIS. Service area buffers around ear, nose and throat
      (ENT) clinics in Ontario were generated to evaluate the proportion of the Ontario
      population with access to these clinics. A survey was also sent to the email
      contact list of HHT Foundation International, targeting people with diagnosed
      HHT, regarding consultation with ENT physicians for epistaxis and timing of HHT
      diagnosis. RESULTS: Primary objective- D-prevalence rates varied among regions,
      from no cases to 1.1 cases per 5000 in large Ontario cities. There were no
      significant differences between urban and rural prevalence rates. Variation in
      prevalence was seen across age groups, with greater prevalence in older adults
      (>=50 years-old) compared with adults 20-49 years-old (0.36 versus 0.26 per 5000,
      p < 0.0005). Secondary objective- Most Ontarians had access to ENT clinics within
      a 30, 60 and 90 minute modeled drive time (92.7%, 97.8% and 98.6%, respectively).
      Nearly 40% of surveyed patients consulted an ENT physician for their epistaxis,
      on average 13.9 +/- 12.2 years prior to being diagnosed with HHT. CONCLUSIONS:
      The prevalence of HHT in Ontario is highly variable across regions and age
      groups, suggesting under-diagnosis. Given that patients with HHT frequently
      consult ENT physicians for epistaxis prior to HHT diagnosis, and that there is
      almost universal access to ENTs in Ontario, we propose targeting ENT clinics as a
      province-wide approach to detect undiagnosed HHT patients and families.

PMID- 25060325
TI  - Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase
      E1alpha in invasive front lesions of colorectal tumors predicts cancer metabolism
      and patient prognosis.
AB  - Although numerous studies have shown the significance of cancer-specific aerobic
      glycolysis, how glycolysis contributes to tumor invasion, a critical phenomenon
      in metastasis, remains unclear. With regard to colorectal cancer (CRC), we
      studied two critical gate enzymes, hexokinase 2 (HK2), which is involved in
      glycolysis, and phosphorylated pyruvate dehydrogenase-E1alpha (p-PDH), which is
      involved in oxidative phosphorylation (OxPhos). Immunohistochemical analyses
      using anti-HK2 and p-PDH antibodies were performed on surgically resected CRC
      samples (n = 104), and the expression in invasive front lesions of tumors was
      assessed. Positive HK2 expression correlated with extensive tumor diameter (P =
      0.0460), advanced tumor depth (P = 0.0395), and presence of lymph node metastasis
      (P = 0.0409). Expression of p-PDH tended to be higher in right-sided CRCs than in
      left-sided CRCs (P = 0.0883). In survival analysis, the combined evaluation of
      positive HK2 and negative p-PDH was associated with reduced recurrence-free
      survival (RFS) (P = 0.0169 in all stages and P = 0.0238 in Stage II and III
      patients, respectively). This evaluation could predict RFS more precisely than
      the independent evaluation. The present study indicated that high HK2 expression
      combined with low p-PDH expression in the invasive front lesions of CRC tumors is
      predictive of tumor aggressiveness and survival of CRC cases.

PMID- 25060327
TI  - Distinct MR Imaging Features of Triple-Negative Breast Cancer with Brain
      Metastasis.
AB  - BACKGROUND: Patients with triple-negative breast cancer (TNBC) are at increased
      risk of brain metastases (BMs). In this retrospective single-institutional study,
      we assessed the radiographic features from a cohort of breast cancer (BC)
      patients with confirmed BM. METHODS: Women diagnosed with BC with BM from January
      1, 1996 to May 31, 2012 were identified through institutional databases. Relevant
      medical records were reviewed to assess patterns of recurrence, treatment,
      magnetic resonance imaging (MRI) features of BM, and survival after BM. The MRI
      finding of BM was classified as solid, necrotic, leptomeningeal spread, or mixed
      type. We assigned the patient into three groups according to histologic subtype
      of primary BC. RESULTS: In total, 62 patients, median age 53 years (range 20-78),
      were identified and specific treatment for BM consisted of radiotherapy, surgical
      resection, and systemic chemotherapy. The initial stage, post-BM survival and
      overall survival were not significantly different. However, cystic necrotic BMs
      appeared on MR images were significantly more associated with the TNBC group.
      CONCLUSION: Patients with BMs from TNBC have distinct MRI features helping the
      assessment of newly developed BM. A large confirmatory study with correlated
      histology in this unique patient population will be required.

PMID- 25060328
TI  - Risks of a lifetime in construction part I: traumatic injuries.
AB  - BACKGROUND: Estimates of occupational risk are typically computed on an annual
      basis. In contrast, this article provides estimates of lifetime risks for fatal
      and nonfatal injuries among construction workers. A companion paper presents
      lifetime risks for occupational illnesses. METHODS: Using 2003-2007 data from
      three large data sources, lifetime risk was computed based on the number of fatal
      and nonfatal injuries per 100 FTEs for a working lifespan of 45 years. RESULTS:
      For a working life in construction, the risk of fatal injuries were approximately
      one death per 200 FTE, and the leading causes were falls and transportation
      incidents. For nonfatal injuries resulting in days away from work, the adjusted
      lifetime risk was approximately 78 per 100 FTEs, and the leading causes were
      contact with objects/equipment, overexertion, and falls to a lower level.
      CONCLUSIONS: Lifetime risk estimates help inform both workers and policymakers.
      Despite improvements over the past decades, risks in construction remain high.

PMID- 25060329
TI  - Elucidation of conformational states, dynamics, and mechanism of binding in human
      kappa-opioid receptor complexes.
AB  - Opioid G protein-coupled receptors (GPCRs) have been implicated in modulating
      pain, addiction, psychotomimesis, mood and memory, among other functions. We have
      employed the recently reported crystal structure of the human kappa-opioid
      receptor (kappa-OR) and performed molecular dynamics (MD), free energy, and ab
      initio calculations to elucidate the binding mechanism in complexes with
      antagonist JDTic and agonist SalA. The two systems were modeled in water and in
      DPPC lipid bilayers, in order to investigate the effect of the membrane upon
      conformational dynamics. MD and Atoms in Molecules (AIM) ab initio calculations
      for the complexes in water showed that each ligand was stabilized inside the
      binding site of the receptor through hydrogen bond interactions that involved
      residues Asp138 (with JDTic) and Gln115, His291, Leu212 (with SalA). The static
      description offered by the crystal structure was overcome to reveal a structural
      rearrangement of the binding pocket, which facilitated additional interactions
      between JDTic and Glu209/Tyr139. The role of Glu209 was emphasized, since it
      belongs to an extracellular loop that covers the binding site of the receptor and
      is crucial for ligand entrapment. The above interactions were retained in
      membrane complexes (SalA forms additional hydrogen bonds with Tyr139/312), except
      the Tyr139 interaction, which is abolished in the JDTic complex. For the first
      time, we report that JDTic alternates between a "V-shape" (stabilized via a water
      mediated intramolecular interaction) and a more extended conformation, a feature
      that offers enough suppleness for effective binding. Moreover, MM-PBSA
      calculations showed that the more efficient JDTic binding to kappa-OR compared to
      SalA (DeltaGJDTic = -31.6 kcal mol(-1), DeltaGSalA = -9.8 kcal mol(-1)) is
      attributed mostly to differences in electrostatic contributions. Importantly, our
      results are in qualitative agreement with the experiments (DeltaGJDTic,exp = 
      14.4 kcal mol(-1), DeltaGSalA,exp = -10.8 kcal mol(-1)). This study provides
      previously unattainable information on the dynamics of human kappa-OR and insight
      on the rational design of drugs with improved pharmacological properties. 

PMID- 25060330
TI  - Brain susceptibility weighted imaging signal changes in acute hemorrhagic anemia:
      an experimental study using a rabbit model.
AB  - BACKGROUND: The aim of this study was to investigate susceptibility-weighted
      imaging (SWI) signal changes in different brain regions in a rabbit model of
      acute hemorrhagic anemia. MATERIAL/METHODS: Ten New Zealand white rabbits were
      used for construction of the model of acute hemorrhagic anemia. Signal
      intensities of SWI images of the bilateral frontal cortex, frontal white matter,
      temporal lobe, and thalamic nuclei were measured. In addition, the cerebral gray
      white contrast and venous structures of the SWI images were evaluated by an
      experienced physician. RESULTS: Repeated bloodletting was associated with
      significant reductions in red blood cell count, hemoglobin concentration,
      hematocrit, pH, and PaCO2, and elevations of blood lactate and PaO2. In normal
      status, the SWI signal intensity was significantly higher in the frontal cortex
      than in the frontal white matter (63.10+/-22.82 vs. 52.50+/-20.29; P<0.05).
      Repeated bloodletting (5 occasions) caused significant (P<0.05) decreases in the
      SWI signals of the frontal cortex (from 63.10+/-22.82 to 37.70+/-4.32), temporal
      lobe (from 52.50+/-20.29 to 42.60+/-5.54), and thalamus (from 60.40+/-20.29 to
      39.40+/-3.47), but was without effect in the frontal white matter. The cerebral
      white-gray contrast and venous structures were clearer after bloodletting than
      before bloodletting. CONCLUSIONS: The effect of hemorrhage on the brain is
      reflected by SWI signal changes in the cerebral cortex and gray matter nuclei.

PMID- 25060331
TI  - The effects of olfactory stimulation and gender differences on pain responses in
      full-term infants.
AB  - AIM: Studies have reported conflicting findings on whether different smells can
      reduce distress when infants undergo painful procedures. Our study assessed the
      impact of vanilla on infants' responses to a painful toe lance, including
      possible gender differences. METHODS: We measured the pain responses of 69 full
      term infants - 34 girls and 35 boys - during toe lance, using two
      multidimensional scales - the Neonatal Facial Coding System and Behavioural
      Indicators of Infant Pain - together with crying duration and hand movements.
      Three sets of data were collected during baseline, toe lance and recovery, while
      the babies were exposed to the odour of vanilla (n = 39) or odourless water (n =
      30). RESULTS: Pain responses increased significantly during toe lance, then
      declined during recovery. Crying duration correlated significantly with finger
      splaying/fisting and both pain scale scores, with boys displaying higher pain
      scores than girls. Vanilla had no impact on pain levels. CONCLUSION: Crying and
      finger splaying/fisting were observable responses that may be useful for
      screening pain or distress in healthy neonates. Increased pain reactions by boys
      may reflect higher irritability. Exposure to an unfamiliar odour did not have a
      calming effect on full-term neonates.

PMID- 25060332
TI  - WITHDRAWN: Inspiratory muscle training with threshold or incentive spirometry:
      Which is the most effective?
AB  - This article has been withdrawn for editorial reasons because the journal will be
      published only in English. In order to avoid duplicated records, this article can
      be found at http://dx.doi.org/10.1016/j.rppnen.2014.05.005. 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- 25060333
TI  - The analysis of a World War I U.S. service member's dental remains recovered in
      France.
AB  - In October 2009, the grave of an unknown World War I (WWI) U.S. service member
      was exhumed in Rembercourt-Sur-Mad Village, in the Lorraine Region of France. The
      skeletal remains and material evidence were accessioned into the Joint POW/MIA
      Accounting Command's (JPAC) Central Identification Laboratory (CIL). The
      personnel records for the associated casualty were requested, received, and
      reviewed. A dental profile was present among the service member's personal
      information. There were multiple points of concordance between the dental records
      of the associated casualty, and the recovered dental remains to include eight
      restored teeth, 15 unrestored teeth, and three antemortem missing teeth.
      Distinctive restorations which compared favorably included a porcelain crown and
      multiple gold foil fillings. All lines of evidence (historical, material
      evidence/personal effects, anthropological, and dental) and the circumstances of
      loss compared positively with the associated casualty. On April 1, 2010, the
      previously unaccounted-for U.S. service member was positively identified and on
      June 23, 2010, was buried with full military honors at Arlington National
      Cemetery. 

PMID- 25060334
TI  - Origins of structural flexibility in protein-based supramolecular polymers
      revealed by DEER spectroscopy.
AB  - Modular assembly of bio-inspired supramolecular polymers is a powerful technique
      to develop new soft nanomaterials, and protein folding is a versatile basis for
      preparing such materials. Previous work demonstrated a significant difference in
      the physical properties of closely related supramolecular polymers composed of
      building blocks in which identical coiled-coil-forming peptides are cross-linked
      by one of two subtly different organic linkers (one flexible and the other
      rigid). Herein, we investigate the molecular basis for this observation by
      isolating a single subunit of the supramolecular polymer chain and probing its
      structure and conformational flexibility by double electron-electron resonance
      (DEER) spectroscopy. Experimental spin-spin distance distributions for two
      different labeling sites coupled with molecular dynamics simulations provide
      insights into how the linker structure impacts chain dynamics in the coiled-coil
      supramolecular polymer. 

PMID- 25060335
TI  - The expression of CAP1 after traumatic brain injury and its role in astrocyte
      proliferation.
AB  - Adenylate cyclase-associated protein 1 (CAP1), a member of cyclase-associated
      proteins involved in the regulation of actin filaments, was recently reported to
      play a role in the pathology of sciatic nerves injury. However, the distribution
      and function of CAP1 in the central nervous system (CNS) remain unclear. To
      investigate whether CAP1 is involved in CNS injury and repair, we used an acute
      traumatic brain injury (TBI) model in adult rats. Western blot analysis and
      immunohistochemistry showed a significant upregulation of CAP1 in ipsilateral
      peritrauma cortex compared with the contralateral and sham-operated ones. Double
      immunofluorescence staining showed that CAP1 was co-expressed with glial
      fibrillary acidic protein (GFAP). In addition, we detected that Ki-67 had
      colocalization with GFAP and CAP1 after TBI. In vitro, during the process of
      lipopolysaccharide (LPS)-induced primary astrocyte proliferation, we observed
      enhanced expression of CAP1. Specially, CAP1-specific siRNA-transfected primary
      astrocytes show significantly decreased ability for proliferation. Together, all
      these data indicated that the change of CAP1 protein expression was associated
      with astrocyte proliferation after the trauma of the central nervous system
      (CNS). 

PMID- 25060336
TI  - Health education and the control of intestinal worm infections in China: a new
      vision.
AB  - BACKGROUND: The transmission of soil-transmitted helminths (STHs) is associated
      with poverty, poor hygiene behaviour, lack of clean water and inadequate waste
      disposal and sanitation. Periodic administration of benzimidazole drugs is the
      mainstay for global STH control but it does not prevent re-infection, and is
      unlikely to interrupt transmission as a stand-alone intervention. FINDINGS: We
      reported recently on the development and successful testing in Hunan province, PR
      China, of a health education package to prevent STH infections in Han Chinese
      primary school students. We have recently commenced a new trial of the package in
      the ethnically diverse Xishuangbanna autonomous prefecture in Yunnan province and
      the approach is also being tested in West Africa, with further expansion into the
      Philippines in 2015. CONCLUSIONS: The work in China illustrates well the direct
      impact that health education can have in improving knowledge and awareness, and
      in changing hygiene behaviour. Further, it can provide insight into the public
      health outcomes of a multi-component integrated control program, where health
      education prevents re-infection and periodic drug treatment reduces prevalence
      and morbidity.

PMID- 25060338
TI  - Differentiation between KPC and IMP carbapenemase needs phenotypic and genotypic
      methods.

PMID- 25060337
TI  - Association between serum free fatty acid levels and nonalcoholic fatty liver
      disease: a cross-sectional study.
AB  - High serum free fatty acid (FFA) levels are associated with metabolic syndrome
      (MS). This study aimed to assess the association of fasting serum FFAs with
      nonalcoholic fatty liver disease (NAFLD) in a Chinese population. A total of 840
      subjects fulfilled the diagnostic criteria of NAFLD and 331 healthy control
      participants were enrolled in this cross-sectional study. Fasting serum FFA
      levels and other clinical and laboratory parameters were measured. NAFLD patients
      had significantly higher serum FFA levels than controls (P < 0.001). Serum FFA
      levels were significantly and positively correlated with parameters of MS,
      inflammation indexes, and markers of hepatocellular damage. Elevated serum FFA
      levels were found in NAFLD subjects with individual components of MS (obesity,
      hypertriglyceridaemia, and hyperglycaemia). Stepwise regression showed that serum
      FFA levels were an independent factor predicting advanced fibrosis (FIB-4 >= 1.3)
      in NAFLD patients. Serum FFA levels correlated with NAFLD and could be used as an
      indicator for predicting advanced fibrosis in NAFLD patients. 

PMID- 25060339
TI  - Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting
      polymer.
AB  - Although electrically stimulated neurite outgrowth on bioelectronic devices is a
      promising means of nerve regeneration, immunogenic scar formation can insulate
      electrodes from targeted cells and tissues, thereby reducing the lifetime of the
      device. Ideally, an electrode material capable of electrically interfacing with
      neurons selectively and efficiently would be integrated without being recognized
      by the immune system and minimize its response. Here we develop a cell membrane
      mimicking conducting polymer possessing several attractive features. This polymer
      displays high resistance towards nonspecific enzyme/cell binding and recognizes
      targeted cells specifically to allow intimate electrical communication over long
      periods of time. Its low electrical impedance relays electrical signals
      efficiently. This material is capable to integrate biochemical and electrical
      stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced
      greatly on this new conducting polymer; in addition, electrically stimulated
      secretion of proteins from primary Schwann cells can also occur on it. 

PMID- 25060340
TI  - Manganese-enhanced magnetic resonance imaging for early detection and
      characterization of breast cancers.
AB  - Very early cancer detection is the key to improving cure. Our objective was to
      investigate manganese (Mn)-enhanced magnetic resonance imaging (MRI) for very
      early detection and characterization of breast cancers. Eighteen NOD scid gamma
      mice were inoculated with MCF7, MDA, and LM2 breast cancer cells and imaged
      periodically on a 3 T scanner beginning on day 6. T1-weighted imaging and T1
      measurements were performed before and 24 hours after administering MnCl2. At the
      last imaging session, Gd-DTPA was administered and tumors were excised for
      histology (hematoxylin-eosin and CD34 staining). All mice, except for two
      inoculated with MCF7 cells, developed tumors. Tumors enhanced uniformly on Mn and
      showed clear borders. Early small tumors (<= 5 mm3) demonstrated the greatest
      enhancement with a relative R1 (1/T1) change of 1.57 +/- 0.13. R1 increases
      correlated with tumor size (r  =  -.34, p  =  .04). Differences in R1 increases
      among the three tumor subtypes were most evident in early tumors. Histology
      confirmed uniform cancer cell distribution within tumor masses and vasculature in
      the periphery, which was consistent with rim-like enhancement on Gd-DTPA. Mn
      enhanced MRI is a promising approach for detecting very small breast cancers in
      vivo and may be valuable for very early cancer detection.

PMID- 25060341
TI  - Transapical access for catheter ablation of left ventricular tachycardia in a
      patient with mechanical aortic and mitral valve prosthesis.

PMID- 25060342
TI  - Using daptomycin in hospitalised patients with cSSTI caused by Staphylococcus
      aureus has an impact on costs.
AB  - BACKGROUND: The aim was to assess the cost impact of daptomycin compared to
      vancomycin treatment in patients hospitalised for complicated skin and soft
      tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus
      aureus infection in the UK. METHODS: A decision model was developed to estimate
      the costs associated with cSSTI treatment. Data on efficacy, treatment duration
      and early discharge from published clinical trials were used, with data gaps on
      standard clinical practice being filled by means of clinician interviews.
      RESULTS: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for
      daptomycin and vancomycin, respectively. A sensitivity analysis suggested that
      modifying the parameters within a reasonable range does not impact on the
      conclusion that the higher cost of daptomycin is likely to be offset by lower
      costs of monitoring and hospitalisation. CONCLUSIONS: This study demonstrates
      that daptomycin not only provides an alternative treatment for multiple resistant
      infections, but may also reduce National Health Service costs.

PMID- 25060343
TI  - Response to the article by Evangelista et al.: Use of a portable gamma camera for
      guiding surgical treatment in locally advanced breast cancer in a post
      neoadjuvant therapy setting. Breast Cancer Res Treat 2014.

PMID- 25060344
TI  - Initial experience of EVAHEART explantation after continuous-flow LVAD off test
      with percutaneous occlusion balloon.
AB  - In contrast to a pulsatile-flow left ventricular assist device (LVAD), an LVAD
      off test for evaluation of cardiac recovery with a continuous-flow device is
      difficult because of intra-circuit backflow from the outflow graft when a device
      is stopped. We report a case of reliable evaluation of cardiac recovery using
      balloon occlusion of the outflow graft, followed by successful removal of a
      continuous-flow EVAHEART LVAD using a minimally invasive approach. 

PMID- 25060345
TI  - Identification of a novel PHEX mutation in a Chinese family with X-linked
      hypophosphatemic rickets using exome sequencing.
AB  - Familial hypophosphatemic rickets (HR), the most common inherited form of
      rickets, is a group of inherited renal phosphate wasting disorders characterized
      by growth retardation, rickets with bone deformities, osteomalacia, poor dental
      development, and hypophosphatemia. The purpose of this study was to identify the
      genetic defect responsible for familial HR in a four-generation Chinese Han
      pedigree by exome sequencing and Sanger sequencing. Clinical features include
      skeletal deformities, teeth abnormalities, hearing impairments and variable serum
      phosphate level in patients of this family. A novel deletion mutation, c.1553delT
      (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase
      homolog gene (PHEX). The mutation is predicted to result in prematurely truncated
      and loss-of-function PHEX protein. Our data suggest that exome sequencing is a
      powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical
      heterogeneity. The findings may also provide new insights into the cause and
      diagnosis of HR, and have implications for genetic counseling and clinical
      management.

PMID- 25060346
TI  - Quantification of adult T-cell leukemia/lymphoma cells using simple four-color
      flow cytometry.
AB  - BACKGROUND: The absolute number of adult T-cell leukemia/lymphoma (ATL) cells in
      peripheral blood is an essential indicator to evaluate disease status. However,
      microscopically counting ATL cells based on morphology requires experience and
      tends to be inaccurate due to the rarity of ATL. METHODS: Based on our research
      showing that acute-type ATL cells are specifically enriched in the CD4+/CD7-
      (CD7N) fraction, a new analytical method to accurately quantify ATL cells was
      established using an internal bead standard and simple four-color flow cytometry.
      This method was verified by comparison with microscopic examination of 49
      peripheral blood samples and used to follow up patients. RESULTS: A strong
      correlation was observed between the number of CD7N cells measured by flow
      cytometry and the number of abnormal lymphocytes measured microscopically by
      experienced technicians [Pearson's R, 0.963; Spearman's rho, 0.921;
      intercorrelation coefficient, 0.962]. The linear regression coefficient was close
      to 1 (beta=1.013). Our method could detect 1 cell/MUL, and the limit of
      quantitation was between 2.9 and 9.8 cells/MUL. The frequency of CD7N cells among
      CD4+ cells changed during chemotherapy, which reflected differences between
      chemosensitive and chemoresistant cases. Kaplan-Meier analysis with a log-rank
      test showed that patients with decreased CD7N proportion after chemotherapy had
      significantly longer disease-specific survival (p=0.003). CONCLUSIONS: Our newly
      established method quantified tumor cells in patients with acute-type ATL.
      Furthermore, this method was useful for assessing the efficacy of chemotherapy,
      and the change of the CD7N proportion could be more important to predict
      prognosis.

PMID- 25060347
TI  - Comparison of approaches and measurement of continuing professional development
      for specialists in laboratory medicine within four European countries.
AB  - BACKGROUND: This study investigated approaches to continuing professional
      development (CPD) for specialists in laboratory medicine within four European
      countries: Croatia, the Czech Republic, Malta and the UK. METHODS: The research
      questions focussed on ascertaining if continued registration/licence was linked
      to CPD and if so, were there requirements for certain amounts and types of CPD
      and for CPD activities to meet specified accreditation criteria. The Professional
      Associations Research Network (PARN) model of CPD measurement was applied to each
      country's registration/licencing body's CPD requirements. RESULTS: Our results
      indicate a spectrum of approaches to CPD within participating countries.
      CONCLUSIONS: It will be necessary for European employers to be familiar with
      these differences and to take them into account for this increasingly mobile
      European workforce.

PMID- 25060348
TI  - Serum fucosylated haptoglobin in chronic liver diseases as a potential biomarker
      of hepatocellular carcinoma development.
AB  - BACKGROUND: Fucosylation is one of the most important glycosylation events
      involved in cancer and inflammation. We previously developed a lectin antibody
      ELISA kit to measure fucosylated haptoglobin (Fuc-Hpt), which we identified as a
      novel cancer biomarker. In this study, we investigated Fuc-Hpt as a biomarker in
      chronic liver diseases, especially in hepatocellular carcinoma (HCC). METHODS: We
      measured serum Fuc-Hpt levels using our ELISA kit in 318 patients with chronic
      liver diseases, including 145 chronic hepatitis (CH) patients, 81 liver cirrhosis
      (LC) patients, and 92 HCC patients. During a long-term follow-up period of 7
      years (1996-2003), Fuc-Hpt levels were measured at three different time points in
      19 HCC patients. Serum Fuc-Hpt levels were also examined with a short-term follow
      up period of 3 years (2009-2012) in 13 HCC patients. RESULTS: Fuc-Hpt levels
      increased with liver disease progression. Patients with LC and HCC showed
      significantly increased Fuc-Hpt levels in comparison to CH patients or healthy
      volunteers. Fuc-Hpt levels tended to be higher in HCC patients than in LC
      patients. Fuc-Hpt was better than alpha-fetoprotein (AFP) and AFP-L3 for
      predicting HCC [diagnosed by computed tomography (CT) or ultrasound] in LC
      patients with long-term follow-up. More than 80% of LC patients with long-term
      follow-up showed increased Fuc-Hpt during hepatocarcinogenesis, and 38% of early
      stage HCC patients with short-term follow-up showed a gradual increase in Fuc-Hpt
      before imaging diagnosis. CONCLUSIONS: These results suggest that Fuc-Hpt is a
      novel and potentially useful biomarker for predicting liver disease progression
      and HCC development.

PMID- 25060349
TI  - A guest in the house: nursing instructors' experiences of the moral distress felt
      by students during inpatient psychiatric clinical rotations.
AB  - Significant research has been done on the impact of moral distress among nurses,
      particularly in acute and intensive care settings. However, little research to
      date has investigated the experiences that nursing students have with moral
      distress. Additionally, there is a dearth of research on the role of nursing
      instructors' perceptions of their responsibilities to their students when
      encountering morally distressing situations. This manuscript describes a
      qualitative study conducted with eight mental health nursing instructors who
      acknowledged a responsibility for helping students deal with moral distress and
      ethical issues, but who also struggled with ways to do so. Additionally,
      instructors expressed frustration with their "guest" status on inpatient
      psychiatric units and their powerlessness to effect moral change in a medical
      model of psychiatric care.

PMID- 25060350
TI  - Biosynthesis of rare ketoses through constructing a recombination pathway in an
      engineered Corynebacterium glutamicum.
AB  - Rare sugars have various known biological functions and potential for
      applications in pharmaceutical, cosmetics, and food industries. Here we designed
      and constructed a recombination pathway in Corynebacterium glutamicum, in which
      dihydroxyacetone phosphate (DHAP), an intermediate of the glycolytic pathway, and
      a variety of aldehydes were condensed to synthesize rare ketoses sequentially by
      rhamnulose-1-phosphate aldolase (RhaD) and fructose-1-phosphatase (YqaB) obtained
      from Escherichia coli. A wild-type strain harboring this artificial pathway had
      the ability to produce D-sorbose and D-psicose using D-glyceraldehyde and glucose
      as the substrates. The tpi gene, encoding triose phosphate isomerase was further
      deleted, and the concentration of DHAP increased to nearly 20-fold relative to
      that of the wild-type. After additional optimization of expression levels from
      rhaD and yqaB genes and of the fermentation conditions, the engineered strain
      SY6(pVRTY) exhibited preferable performance for rare ketoses production. Its
      yield increased to 0.59 mol/mol D-glyceraldehyde from 0.33 mol/mol D
      glyceraldehyde and productivity to 2.35 g/L h from 0.58 g/L h. Moreover, this
      strain accumulated 19.5 g/L of D-sorbose and 13.4 g/L of D-psicose using a fed
      batch culture mode under the optimal conditions. In addition, it was verified
      that the strain SY6(pVRTY) meanwhile had the ability to synthesize C4, C5, C6,
      and C7 rare ketoses when a range of representative achiral and homochiral
      aldehydes were applied as the substrates. Therefore, the platform strain
      exhibited the potential for microbial production of rare ketoses and deoxysugars.

PMID- 25060352
TI  - Investigation of gastric cancers in nude mice using X-ray in-line phase contrast
      imaging.
AB  - BACKGROUND: This paper is to report the new imaging of gastric cancers without
      the use of imaging agents. Both gastric normal regions and gastric cancer regions
      can be distinguished by using the principal component analysis (PCA) based on the
      gray level co-occurrence matrix (GLCM). METHODS: Human gastric cancer BGC823
      cells were implanted into the stomachs of nude mice. Then, 3, 5, 7, 9 or 11 days
      after cancer cells implantation, the nude mice were sacrificed and their stomachs
      were removed. X-ray in-line phase contrast imaging (XILPCI), an X-ray phase
      contrast imaging method, has greater soft tissue contrast than traditional
      absorption radiography and generates higher-resolution images. The gastric
      specimens were imaged by an XILPCIs' charge coupled device (CCD) of 9 MUm image
      resolution. The PCA of the projective images' region of interests (ROIs) based on
      GLCM were extracted to discriminate gastric normal regions and gastric cancer
      regions. Different stages of gastric cancers were classified by using support
      vector machines (SVMs). RESULTS: The X-ray in-line phase contrast images of nude
      mice gastric specimens clearly show the gastric architectures and the details of
      the early gastric cancers. The phase contrast computed tomography (CT) images of
      nude mice gastric cancer specimens are better than the traditional absorption CT
      images without the use of imaging agents. The results of the PCA of the texture
      parameters based on GLCM of normal regions is (F1+F2) >8.5, but those of cancer
      regions is (F1+F2) <8.5. The classification accuracy is 83.3% that classifying
      gastric specimens into different stages using SVMs. CONCLUSIONS: This is a very
      preliminary feasibility study. With further researches, XILPCI could become a
      noninvasive method for future the early detection of gastric cancers or medical
      researches.

PMID- 25060351
TI  - Potential role of hematopoietic pre-B-cell leukemia transcription factor
      interacting protein in oral carcinogenesis.
AB  - BACKGROUND: Hematopoietic pre-B-cell leukemia transcription factor-interacting
      protein (HPIP) is a corepressor of pre-B-cell leukemia homeobox (PBX) 1 and is
      known to play a role in hematopoiesis. Recently, HPIP was demonstrated to promote
      breast cancer cell proliferation and hepatocellular carcinoma growth. Moreover,
      it has been revealed that homeobox and PBX proteins, the expression of which is
      regulated by HPIP, play key roles in cancer of various organs, including oral
      squamous cell carcinoma (OSCC). Nevertheless, there has not been any study
      regarding the role of HPIP in OSCC. This study investigated the expression of
      HPIP in normal oral mucosa, epithelial precursor lesion (OEPL), and OSCC, and the
      functional roles of HPIP in OSCC cells and normal keratinocytes. MATERIALS AND
      METHODS: Immunohistochemical analysis of HPIP, Ki-67, and involucrin was
      performed in OSCC specimens, and the change in involucrin expression following
      RNA interference treatment against HPIP was examined by quantitative RT-PCR and
      Western blot analysis in SCC9 and NHEK cells undergoing extracellular calcium
      induced differentiation. Matrigel transwell and cell proliferation assays for
      both cell lines transfected with HPIP siRNA were also conducted. RESULTS: HPIP
      expression increased in OEPL and OSCC specimens. In vitro analysis revealed that
      HPIP suppressed differentiation and proliferation of SCC9 cells and transwell
      migration of NHEK cells, while HPIP promoted invasion of SCC9 and proliferation
      of NHEK cells. However, HPIP has no significant effect on NHEK cell
      differentiation. CONCLUSION: HPIP may play a critical role in oral carcinogenesis
      and is thus a potential target for anticancer therapy, with particular emphasis
      on its involvement in differentiation and migration/metastasis.

PMID- 25060353
TI  - Does the volatile hydrocarbon profile differ between the sexes: a case study on
      five aphidophagous ladybirds.
AB  - Insect hydrocarbons (HCs) primarily serve as a waterproofing cuticular layer and
      function extensively in chemical communication by facilitating species, sex, and
      colony recognition. In this study, headspace solid-phase microextraction is
      employed for investigating the sex-specific volatile HC profile of five ladybirds
      collected from Lucknow, India namely, Coccinella septempunctata (L.), Coccinella
      transversalis (Fabr.), Menochilus sexmaculatus (Fabr.), Propylea dissecta
      (Mulsant), and Anegleis cardoni (Weise) for the first time. Major compounds
      reported in C. septempunctata, C. transversalis, and A. cardoni are methyl
      branched saturated HCs, whereas in M. sexmaculatus, and P. dissecta, they are
      unsaturated HCs. Other than A. cardoni, both the sexes of the other four
      ladybirds had similar compounds at highest peak but with statistically
      significant differences. However, in A. cardoni, which is a beetle with a narrow
      niche, the major compound in both male and female was different. The difference
      in volatile HC profile of the sexes of the five ladybirds indicates that gender
      specific differences primarily exist due to quantitative differences in chemicals
      with only very few chemicals being unique to a gender. This variation in
      semiochemicals might have a role in behavioral or ecological aspects of the
      studied ladybirds. 

PMID- 25060354
TI  - Alpha-mangostin promotes myoblast differentiation by modulating the gene
      expression profile in C2C12 cells.
AB  - Alpha-mangostin, a xanthone contained mostly in mangosteen pericarp, has been
      reported to exert various biological functions. However, little is known about
      involvement of this xanthone in the muscle differentiation process. Here, we
      report the effect of alpha-mangostin on murine skeletal muscle-derived C2C12
      myoblasts. alpha-mangostin stimulated myoblast differentiation leading to myotube
      formation. DNA microarray analysis revealed that genes associated with myoblast
      differentiation and muscle cell component formation were up-regulated in alpha
      mangostin-treated cells. These results indicate that alpha-mangostin promotes
      myoblast differentiation through modulating the gene-expression profile in
      myoblasts. 

PMID- 25060355
TI  - Transumbilical laparoendoscopic single-site ureteral reimplantation.
AB  - OBJECTIVE: To analyze the outcomes of umbilical laparoendoscopic single-site
      (LESS) ureteral reimplantation using a reusable single-port platform. MATERIAL
      AND METHOD: The casuistic of LESS ureteral reimplantation in 5 patients is
      presented. The surgical technique using KeyPort system (reusable umbilical single
      site platform) is described. Dissection, suctioning and suturing by
      minilaparoscopy through 3.5mm accessory port in the iliac fossa are performed.
      Operative and postoperative outcomes are presented. The median follow-up at time
      of analysis was 11 +/- 14 months. RESULTS: The median age of patients was a 49 +/
      34 year; male-female ratio was 1:1.15. Left surgery was carried out in all
      cases. In 4 patients, the etiology was secondary to stenosis (3 iatrogenic and 1
      pelvic endometriosis). In the remaining case, the procedure was performed after
      excision of a symptomatic adult ureterocele. In all cases, bladder catheter and
      double-J ureteral catheter were inserted for 7 +/- 3 and 30 +/- 15 days and then
      removed. No conversion to convectional laparoscopic or open surgery occurred. The
      surgery time was 145 +/- 60 min, and intraoperative bleeding was 100 +/- 75 cc.
      Neither transfusion nor high analgesia was necessary. No postoperative
      complications, minor or major, have been reported. Hospital stay was 2 +/- 0.5
      days. In any patient, restenosis or worsening of renal function occurred.
      CONCLUSIONS: In experimented centers, transumbilical laparoendoscopic single-site
      ureteroneocystostomy is a safe alternative with comparable results to
      conventional laparoscopy and an excellent cosmetic result at low cost thanks to
      device reuse.

PMID- 25060356
TI  - Clinical analysis of port-wine stain in 130 Chinese patients treated by long
      pulsed 1064-nm Nd: YAG laser.
AB  - BACKGROUND: The long-pulsed 1064-nm Nd: YAG laser is effective for treating port
      wine stain (PWS). This study evaluated the efficacy and safety of Nd: YAG laser
      in treating PWS in Chinese patients. METHODS: A retrospective study of 130 PWS
      patients treated with long-pulsed 1064-nm Nd: YAG laser from 2009 to 2011.
      RESULTS: After treatment, 2, 15, 64, and 19 percent of patients experienced <
      25%, 25-49%, 50-75%, and > 75% lesion clearance, respectively. Purple lesions
      showed more significant improvement than pink lesions. The initial response was
      blistering, dark gray coloration, or light gray coloration, the best improvement
      occurred in 100% (27/27), 82.5% (52/63), and 72.5% (29/40), respectively.
      Patients older than 20 years showed the best improvement (37/38, 97.4%), followed
      by those 10-20 years old (20/24, 83.3%), 1-9 years old (23/29, 79.3%) and less
      than 1 year old (28/39, 71.8%). Patients with neck lesions had the best outcome
      (47/48, 97.9%), followed by those with lesions on the face (43/53, 81.2%),
      extremities (13/18, 72.2%), and trunk (5/11, 45.5%). The common adverse side
      effects were blistering and pigment changes. CONCLUSIONS: 1064-nm Nd: YAG laser
      is effective and safe for the treatment of PWS. The efficacy is affected by the
      age of the patient, the color and location of the lesions, and immediate
      responses to the laser.

PMID- 25060357
TI  - Exploration of ethical debates through Desai's The Inheritance of Loss,
      Ishiguro's Never Let Me Go and Smith's On Beauty.
AB  - This essay examines debates over alternative ethical formulations that break from
      the Kantian model through contemporary fiction--Kiran Desai's The Inheritance of
      Loss (2006), Kazuo Ishiguro's Never Let Me Go (2005) and Zadie Smith's On Beauty
      (2005). The essay returns to the theory, the ethics of care, put forward by Carol
      Gilligan in In a Different Voice (1982), which has regained significance in the
      context of questions surrounding care in contemporary ethical thinking. While the
      three novels are concerned with ideas of care, beauty, justice and the tyranny of
      the mainstream, this essay examines particular themes in particular texts which
      suggest that ideas with otherwise subversive potential--like care or beauty or
      justice--lose their radicalism when they are incorporated within the impersonal,
      masculinist mainstream. Carol Gilligan's feminine ethics of care, with its
      respect for the particular, is not only still important as the stimulus to
      thinking about alternatives to overarching ethical discourses, but it could also
      re-confer these concepts of care, beauty and justice their revolutionary
      potential.

PMID- 25060358
TI  - The changing reality of urothelial bladder cancer: should non-squamous variant
      histology be managed as a distinct clinical entity?
AB  - OBJECTIVES: To assess the effect of non-squamous differentiation (non-SQD)
      variant histology on survival in muscle-invasive bladder urothelial cancer (UC).
      PATIENTS AND METHODS: A cohort of 411 radical cystectomy (RC) cases performed
      with curative intent for muscle-invasive primary UC was identified between 2008
      and June 2013. Survival analysis was evaluated using Kaplan-Meier methodology
      comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD
      variants). Multivariable cox proportional hazards regression assessed all-cause
      and disease-specific mortality. RESULTS: Of the 411 RC cases, 77 (19%) had non
      SQD variant histology. The median overall survival (OS) for non-SQD variant
      histology was 28 months, whereas the NV+SQD group had not reached the median OS
      at 74 months (log-rank test P < 0.001). After adjusting for sex, age,
      pathological stage, and any systemic chemotherapy, patients with non-SQD variant
      histology at RC had a 1.57-times increased adjusted risk of all-cause mortality
      (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P =
      0.030) compared with NV+SQD patients. CONCLUSIONS: While SQD behaves similarly to
      NV, non-SQD variant histology portends worse OS and disease-specific survival
      regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non
      SQD variants of UC could perhaps be considered a distinct clinical entity in UC
      with goals for developing new treatment algorithms through novel clinical trials.

PMID- 25060359
TI  - Cerebral blood volume estimation by ferumoxytol-enhanced steady-state MRI at 9.4
      T reveals microvascular impact of alpha1 -adrenergic receptor antibodies.
AB  - Cerebrovascular abnormality is frequently accompanied by cognitive dysfunctions,
      such as dementia. Antibodies against the alpha1 -adrenoceptor (alpha1 -AR) can be
      found in patients with Alzheimer's disease with cerebrovascular disease, and have
      been shown to affect the larger vessels of the brain in rodents. However, the
      impact of alpha1 -AR antibodies on the cerebral vasculature remains unclear. In
      the present study, we established a neuroimaging method to measure the relative
      cerebral blood volume (rCBV) in small rodents with the ultimate goal to detect
      changes in blood vessel density and/or vessel size induced by alpha1 -AR
      antibodies. For this purpose, mapping of R2 * and R2 was performed using MRI at
      9.4 T, before and after the injection of intravascular iron oxide particles
      (ferumoxytol). The change in the transverse relaxation rates (DeltaR2 *, DeltaR2
      ) showed a significant rCBV decrease in the cerebrum, cortex and hippocampus of
      rats (except hippocampal DeltaR2 ), which was more pronounced for DeltaR2 * than
      for DeltaR2 . Immunohistological analyses confirmed that the alpha1 -AR antibody
      induced blood vessel deficiencies. Our findings support the hypothesis that
      alpha1 -AR antibodies lead to cerebral vessel damage throughout the brain, which
      can be monitored by MRI-derived rCBV, a non-invasive neuroimaging method. This
      demonstrates the value of rCBV estimation by ferumoxytol-enhanced MRI at 9.4 T,
      and further underlines the significance of this antibody in brain diseases
      involving vasculature impairments, such as dementia.

PMID- 25060360
TI  - Adverse drug reactions - examples of detection of rare events using databases.
AB  - It is recognised that randomised controlled trials are not feasible for capturing
      rare adverse events. There is an increasing trend towards observational research
      methodologies using large population-based health databases. These databases
      offer more scope for adequate sample sizes, allowing for comprehensive patient
      characterisation and assessment of the associated factors. While direct causality
      cannot be established and confounders cannot be ignored, databases present an
      opportunity to explore and quantify rare events. The use of databases for the
      detection of rare adverse events in the following conditions, sudden death
      associated with attention deficit hyperactivity disorder (ADHD) treatment,
      retinal detachment associated with the use of fluoroquinolones and toxic
      epidermal necrolysis associated with drug exposure, are discussed as examples. In
      general, rare adverse events tend to have immediate and important clinical
      implications and may be life-threatening. An understanding of the causative
      factors is therefore important, in addition to the research methodologies and
      database platforms that enable the undertaking of the research. 

PMID- 25060361
TI  - Genetic manipulation of the ghrelin signaling system in male mice reveals bone
      compartment specificity of acylated and unacylated ghrelin in the regulation of
      bone remodeling.
AB  - Ghrelin receptor-deficient (Ghsr-/-) mice that lack acylated ghrelin (AG)
      signaling retain a metabolic response to unacylated ghrelin (UAG). Recently, we
      showed that Ghsr-deficiency affects bone metabolism. The aim of this study was to
      further establish the impact of AG and UAG on bone metabolism. We compared bone
      metabolism in Ghsr-/- (lacking only AG signaling) and ghrelin-deficient (Ghrl-/-;
      both AG and UAG deficient) male mice. Ghrl-/- mice had lower cortical bone mass,
      whereas Ghsr-/- mice had lower trabecular bone mass. This demonstrates bone
      compartment-specific effects of AG and a role for UAG in bone metabolism. Also,
      Ghrl-/- but not Ghsr-/- mice had increased bone formation rate and increased
      osteogenic stem cell numbers in their bone marrow. In ex vivo bone marrow
      cultures both AG and UAG inhibited osteoblast differentiation. This indicated
      that bone resorption must be increased in these mice. Accordingly,
      osteoclastogenesis rate was faster in bone marrow cultures from Ghsr-/- and Ghrl
      /- mice, and osteoclast formation was inhibited by AG signaling and partially
      suppressed by UAG. In osteoblast cultures, AG markedly induced osteoprotegerin
      gene expression and both peptides reduced RANKL/osteoprotegerin ratio. These data
      describe unique cell-type specific effects of AG and UAG within a single tissue,
      supporting a tight and complex control of bone formation and resorption as well
      as a link between nutrition and bone metabolism. The balance between AG and UAG
      actions in the bone marrow may lead to bone compartmental-specific effects.

PMID- 25060362
TI  - Ghrelin induces leptin resistance by activation of suppressor of cytokine
      signaling 3 expression in male rats: implications in satiety regulation.
AB  - The anorexigenic adipocyte-derived hormone leptin and the orexigenic hormone
      ghrelin act in opposition to regulate feeding behavior via the vagal afferent
      pathways. The mechanisms by which ghrelin exerts its inhibitory effects on leptin
      are unknown. We hypothesized that ghrelin activates the exchange protein
      activated by cAMP (Epac), inducing increased SOCS3 expression, which negatively
      affects leptin signal transduction and neuronal firing in nodose ganglia (NG)
      neurons. We showed that 91 +/- 3% of leptin receptor (LRb) -bearing neurons
      contained ghrelin receptors (GHS-R1a) and that ghrelin significantly inhibited
      leptin-stimulated STAT3 phosphorylation in rat NG neurons. Studies of the
      signaling cascades used by ghrelin showed that ghrelin caused a significant
      increase in Epac and suppressor of cytokine signaling 3 (SOCS3) expression in
      cultured rat NG neurons. Transient transfection of cultured NG neurons to silence
      SOCS3 and Epac genes reversed the inhibitory effects of ghrelin on leptin
      stimulated STAT3 phosphorylation. Patch-clamp studies and recordings of single
      neuronal discharges of vagal primary afferent neurons showed that ghrelin
      markedly inhibited leptin-stimulated neuronal firing, an action abolished by
      silencing SOCS3 expression in NG. Plasma ghrelin levels increased significantly
      during fasting. This was accompanied by enhanced SOCS3 expression in the NG and
      prevented by treatment with a ghrelin antagonist. Feeding studies showed that
      silencing SOCS3 expression in the NG reduced food intake evoked by endogenous
      leptin. We conclude that ghrelin exerts its inhibitory effects on leptin
      stimulated neuronal firing by increasing SOCS3 expression. The SOCS3 signaling
      pathway plays a pivotal role in ghrelin's inhibitory effect on STAT3
      phosphorylation, neuronal firing, and feeding behavior.

PMID- 25060364
TI  - Heterozygous deletion of ventral anterior homeobox (vax1) causes subfertility in
      mice.
AB  - The known genetic causes of idiopathic hypogonadotropic hypogonadism (IHH) are
      often associated with the loss of GnRH neurons, leading to the disruption of the
      hypothalamic pituitary gonadal axis and subfertility. The majority of IHH cases
      have unknown origins and likely arise from compound mutations in more than one
      gene. Here we identify the homeodomain transcription factor ventral anterior
      homeobox1 (Vax1) as a potential genetic contributor to polygenic IHH. Although
      otherwise healthy, male and female Vax1 heterozygous (HET) mice are subfertile,
      indicating dosage sensitivity for the Vax1 allele. Although Vax1 mRNA is
      expressed in the pituitary, hypothalamus, and testis, we did not detect Vax1 mRNA
      in the sperm, ovary, or isolated pituitary gonadotropes. Whereas Vax1 HET females
      produced normal numbers of superovulated oocytes, corpora lutea numbers were
      reduced along with a slight increase in circulating basal LH and estrogen. The
      subfertility originated in the hypothalamus in which kisspeptin and GnRH
      transcripts were altered along with a substantial reduction of GnRH neuron
      number. Although the pituitary responded normally to a GnRH challenge, diestrus
      females had reduced LHbeta and FSHbeta in diestrus. Furthermore, Vax1 HET males
      had reduced GnRH mRNA and neuron numbers, whereas the pituitary had normal
      transcript levels and response to GnRH. Interestingly, the Vax1 HET males had an
      88% reduction of motile sperm. Taken together, our data suggest that Vax1 HET
      subfertility originates in the hypothalamus by disrupting the hypothalamic
      pituitary-gonadal axis. In addition, male subfertility may also be due to an
      unknown effect of Vax1 in the testis.

PMID- 25060363
TI  - Polybrominated diphenyl ether (DE-71) interferes with thyroid hormone action
      independent of effects on circulating levels of thyroid hormone in male rats.
AB  - Polybrominated diphenyl ethers (PBDEs) are routinely found in human tissues
      including cord blood and breast milk. PBDEs may interfere with thyroid hormone
      (TH) during development, which could produce neurobehavioral deficits. An
      assumption in experimental and epidemiological studies is that PBDE effects on
      serum TH levels will reflect PBDE effects on TH action in tissues. To test
      whether this assumption is correct, we performed the following experiments.
      First, five concentrations of diphenyl ether (0-30 mg/kg) were fed daily to
      pregnant rats to postnatal day 21. PBDEs were measured in dam liver and heart to
      estimate internal dose. The results were compared with a separate study in which
      four concentrations of propylthiouracil (PTU; 0, 1, 2, and 3 ppm) was provided to
      pregnant rats in drinking water for the same duration as for diphenyl ether. PBDE
      exposure reduced serum T4 similar in magnitude to PTU, but serum TSH was not
      elevated by PBDE. PBDE treatment did not affect the expression of TH response
      genes in the liver or heart as did PTU treatment. PTU treatment reduced T4 in
      liver and heart, but PBDE treatment reduced T4 only in the heart. Tissue PBDEs
      were in the micrograms per gram lipid range, only slightly higher than observed
      in human fetal tissues. Thus, PBDE exposure reduces serum T4 but does not produce
      effects on tissues typical of low TH produced by PTU, demonstrating that the
      effects of chemical exposure on serum T4 levels may not always be a faithful
      proxy measure of chemical effects on the ability of thyroid hormone to regulate
      development and adult physiology.

PMID- 25060366
TI  - Trends in acute myocardial infarction in young patients and differences by sex
      and race, 2001 to 2010.
AB  - BACKGROUND: Various national campaigns launched in recent years have focused on
      young women with acute myocardial infarctions (AMIs). Contemporary longitudinal
      data about sex differences in clinical characteristics, hospitalization rates,
      length of stay (LOS), and mortality have not been examined. OBJECTIVES: This
      study sought to determine sex differences in clinical characteristics,
      hospitalization rates, LOS, and in-hospital mortality by age group and race among
      young patients with AMIs using a large national dataset of U.S. hospital
      discharges. METHODS: Using the National Inpatient Sample, clinical
      characteristics, AMI hospitalization rates, LOS, and in-hospital mortality were
      compared for patients with AMI across ages 30 to 54 years, dividing them into 5
      year subgroups from 2001 to 2010, using survey data analysis techniques. RESULTS:
      A total of 230,684 hospitalizations were identified with principal discharge
      diagnoses of AMI in 30- to 54-year-old patients from Nationwide Inpatient Sample
      data, representing an estimated 1,129,949 hospitalizations in the United States
      from 2001 to 2010. No statistically significant declines in AMI hospitalization
      rates were observed in the age groups <55 years or stratified by sex. Prevalence
      of comorbidities was higher in women and increased among both sexes through the
      study period. Women had longer LOS and higher in-hospital mortality than men
      across all age groups. However, observed in-hospital mortality declined
      significantly for women from 2001 to 2010 (from 3.3% to 2.3%, relative change
      30.5%; p for trend < 0.0001) but not for men (from 2% to 1.8%, relative change
      8.6%; p for trend = 0.60). CONCLUSIONS: AMI hospitalization rates for young
      people have not declined over the past decade. Young women with AMIs have more
      comorbidity, longer LOS, and higher in-hospital mortality than young men,
      although their mortality rates are decreasing.

PMID- 25060367
TI  - Targeting priority populations to reduce disparities in cardiovascular care:
      health equity for all.

PMID- 25060365
TI  - Cobalt-catalyzed, aminoquinoline-directed C(sp2)-H bond alkenylation by alkynes.
AB  - A method for cobalt-catalyzed, aminoquinoline- and picolinamide-directed C(sp(2))
      H bond alkenylation by alkynes was developed. The method shows excellent
      functional-group tolerance and both internal and terminal alkynes are competent
      substrates for the coupling. The reaction employs a Co(OAc)2?4 H2O catalyst,
      Mn(OAc)2 co-catalyst, and oxygen (from air) as a terminal oxidant.

PMID- 25060368
TI  - Detection of myocardial injury by CMR after transcatheter aortic valve
      replacement.
AB  - BACKGROUND: Myocardial injury after transcatheter aortic valve replacement (TAVR)
      is common, but its cause and relationship to the extent of myocardial tissue loss
      remain unclear. OBJECTIVES: This study sought to examine the incidence and degree
      of ischemic myocardial damage using cardiac magnetic resonance imaging and
      myocardial biomarkers in patients undergoing TAVR. METHODS: Patients with severe
      aortic stenosis (n = 61) underwent cardiac magnetic resonance imaging before and
      after TAVR for the assessment of new myocardial injury. High-sensitivity cardiac
      troponin T and creatine kinase-myocardial band were measured before and at 24,
      48, and 72 h after TAVR. RESULTS: After TAVR, new myocardial late enhancement
      (LE) with an ischemic pattern occurred in 11 patients (18%), with a mean mass of
      3.7 g (interquartile range: 1.2 to 6 g) or 1.8% (interquartile range: 1.3% to
      4.1%) of the left ventricular mass. Patients with new LE had a decreased left
      ventricular function (ejection fraction: pre, 55.5 +/- 14.1% vs. post, 45.3 +/-
      14.9%; p = 0.001). In patients without new LE, no differences were observed
      (ejection fraction: pre, 53.9 +/- 17.3% vs. post, 54.6 +/- 16.3%; p = NS) after
      TAVR. CONCLUSIONS: New ischemic-type myocardial LE after TAVR can be observed in
      a notable proportion of patients and is assumed to be of embolic origin. Patients
      with new LE feature a significant decrease in left ventricular function at
      discharge.

PMID- 25060369
TI  - Myocardial damage after TAVR assessed with CMR: a new piece in a puzzle?

PMID- 25060370
TI  - Variability of individual platelet reactivity over time in patients treated with
      clopidogrel: insights from the ELEVATE-TIMI 56 trial.
AB  - BACKGROUND: The degree of antiplatelet response to clopidogrel has been
      associated with clinical outcomes. Studies have investigated whether adjustment
      of antiplatelet therapies based on a single platelet function test is beneficial.
      OBJECTIVES: The aim of the study was to test the stability of platelet reactivity
      measurements over time among patients treated with standard and double doses of
      clopidogrel. METHODS: The ELEVATE-TIMI 56 (Escalating Clopidogrel by Involving a
      Genetic Strategy-Thrombolysis In Myocardial Infarction 56) investigators
      genotyped 333 patients with coronary artery disease and randomized them to
      various clopidogrel regimens. Patients with at least 2 platelet function results
      on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed.
      Platelet aggregation was measured using P2Y12 reaction units (PRU). RESULTS: In
      total, the mean platelet reactivity and the total number of nonresponders (PRU
      >=230) with clopidogrel did not change between 2 periods for the 75-mg (22.4% vs.
      21.9%; p = 0.86) and 150-mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In
      contrast, when evaluating each patient individually, 15.7% of patients taking
      clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their
      responder status when tested at 2 different time points (p < 0.001). Despite
      being treated with the same dose of clopidogrel, >40% of patients had a change in
      PRU >40 on serial sampling, which approximates the average PRU difference caused
      by increasing the clopidogrel dose from 75 mg to 150 mg. CONCLUSIONS:
      Measurements of platelet reactivity vary over time in a significant proportion of
      patients. Thus, treatment adjustment according to platelet function testing at a
      single time point might not be sufficient for guiding antiplatelet therapy in
      clinical or research settings. (Escalating Clopidogrel by Involving a Genetic
      Strategy-Thrombolysis In Myocardial Infarction 56 [ELEVATE-TIMI 56];
      NCT01235351).

PMID- 25060371
TI  - The chronovariability of platelet reactivity: a hurdle in the road to
      personalized antiplatelet therapy?

PMID- 25060373
TI  - Infections post-cardiac surgery: new information during challenging times.

PMID- 25060372
TI  - Management practices and major infections after cardiac surgery.
AB  - BACKGROUND: Infections are the most common noncardiac complication after cardiac
      surgery, but their incidence across a broad range of operations, as well as the
      management factors that shape infection risk, remain unknown. OBJECTIVES: This
      study sought to prospectively examine the frequency of post-operative infections
      and associated mortality, and modifiable management practices predictive of
      infections within 65 days from cardiac surgery. METHODS: This study enrolled
      5,158 patients and analyzed independently adjudicated infections using a
      competing risk model (with death as the competing event). RESULTS: Nearly 5% of
      patients experienced major infections. Baseline characteristics associated with
      increased infection risk included chronic lung disease (hazard ratio [HR]: 1.66;
      95% confidence interval [CI]: 1.21 to 2.26), heart failure (HR: 1.47; 95% CI:
      1.11 to 1.95), and longer surgery (HR: 1.31; 95% CI: 1.21 to 1.41). Practices
      associated with reduced infection risk included prophylaxis with second
      generation cephalosporins (HR: 0.70; 95% CI: 0.52 to 0.94), whereas post
      operative antibiotic duration >48 h (HR: 1.92; 95% CI: 1.28 to 2.88), stress
      hyperglycemia (HR: 1.32; 95% CI: 1.01 to 1.73); intubation time of 24 to 48 h
      (HR: 1.49; 95% CI: 1.04 to 2.14); and ventilation >48 h (HR: 2.45; 95% CI: 1.66
      to 3.63) were associated with increased risk. HRs for infection were similar with
      either <24 h or <48 h of antibiotic prophylaxis. There was a significant but
      differential effect of transfusion by surgery type (excluding left ventricular
      assist device procedures/transplant) (HR: 1.13; 95% CI: 1.07 to 1.20). Major
      infections substantially increased mortality (HR: 10.02; 95% CI: 6.12 to 16.39).
      CONCLUSIONS: Major infections dramatically affect survival and readmissions.
      Second-generation cephalosporins were strongly associated with reduced major
      infection risk, but optimal duration of antibiotic prophylaxis requires further
      study. Given practice variations, considerable opportunities exist for improving
      outcomes and preventing readmissions. (Management Practices and Risk of Infection
      Following Cardiac Surgery; NCT01089712).

PMID- 25060374
TI  - Characterization of lipid-rich aortic plaques by intravascular photoacoustic
      tomography: ex vivo and in vivo validation in a rabbit atherosclerosis model with
      histologic correlation.
AB  - BACKGROUND: Histologic studies have demonstrated that lipid content and its
      spatial distribution is related to plaque vulnerability. However, in vivo imaging
      is still limited. Photoacoustic imaging may provide novel in vivo insights into
      these lipid-rich plaques. OBJECTIVES: This study sought to examine whether
      intravascular photoacoustic tomography (IVPAT) allows localization and
      quantification of lipid content in atherosclerotic plaques. METHODS: Rabbits fed
      with a high-fat/high-cholesterol diet served as the atherosclerotic model.
      Catheter-based IVPAT was used to evaluate pixel-based lipid relative
      concentration (LRC) of the vessel wall. The aorta of 4 groups of rabbits (n = 12)
      were examined ex vivo with IVPAT after 0, 5, 10, and 15 weeks of a high-fat diet,
      respectively. Six rabbits underwent 3-dimensional (3D) IVPAT after 20 weeks of
      the high-fat diet. Three rabbits were examined in vivo using IVPAT without
      interruption of blood flow. Concentration-based lipid map and quantitative index
      were calculated. For subsequent histologic correlation, all specimens were
      evaluated with Oil Red O staining. RESULTS: Cross-sectional LRC maps allowed
      visualization of concentration and depth information of lipid content in the
      atherosclerotic plaques. Lipid accumulation within plaque, assessed by the
      maximum LRC, mean LRC, and high lipid content area correlated to duration of a
      high-fat diet. Three-dimensional LRC maps enabled overall evaluation of focal
      plaques in an intact explanted aorta including spatial and structural features.
      In vivo-obtained LRC maps accurately showed the structure of lipid core with high
      contrast. Ex vivo and in vivo IVPAT results were highly consistent with
      histological results. CONCLUSIONS: In an animal model, IVPAT allowed
      characterization of spatial and quantitative features of lipid-rich plaques.

PMID- 25060375
TI  - Intravascular photoacoustic tomography of coronary atherosclerosis: riding the
      waves of light and sound.

PMID- 25060377
TI  - Paradoxical embolism.
AB  - Paradoxical embolism is an important clinical entity among patients with venous
      thromboembolism in the presence of intracardiac or pulmonary shunts. The clinical
      presentation is diverse and potentially life-threatening. Although the serious
      nature and complications of paradoxical embolism are recognized, the disease
      entity is still rarely considered and remains under-reported. This paper provides
      an overview on the different clinical manifestations of paradoxical embolism,
      describes the diagnostic tools for the detection of intracardiac and pulmonary
      shunts, reviews therapeutic options, and summarizes guideline recommendations for
      the secondary prevention of paradoxical embolism. 

PMID- 25060378
TI  - At the heart of global development.

PMID- 25060376
TI  - 2014 hypertension recommendations from the eighth joint national committee panel
      members raise concerns for elderly black and female populations.
AB  - A report from panel members appointed to the Eighth Joint National Committee
      titled "2014 Evidence-Based Guideline for the Management of High Blood Pressure
      in Adults" has garnered much attention due to its major change in recommendations
      for hypertension treatment for patients >=60 years of age and for their treatment
      goal. In response, certain groups have opposed the decision to initiate
      pharmacologic treatment to lower blood pressure (BP) at systolic BP >=150 mm Hg
      and treat to a goal systolic BP of <150 mm Hg in the general population age >=60
      years. This paper contains 3 sections-an introduction followed by the opinions of
      2 writing groups-outlining objections to or support of maintaining this proposed
      strategy in certain at-risk populations, namely African Americans, women, and the
      elderly. Several authors argue for maintaining current targets, as opposed to
      adopting the new recommendations, to allow for optimal treatment for older women
      and African Americans, helping to close sex and race/ethnicity gaps in
      cardiovascular disease morbidity and mortality.

PMID- 25060379
TI  - Medical malpractice litigation: a fellow's perspective.

PMID- 25060380
TI  - In regard to the TERISA trial.

PMID- 25060381
TI  - Reply: In regard to the TERISA trial.

PMID- 25060382
TI  - Resting heart rate: an independent predictor of congestive heart failure.

PMID- 25060383
TI  - Reply: Resting heart rate: an independent predictor of congestive heart failure.

PMID- 25060384
TI  - Tubular carcinoma of the breast: axillary involvement and prognostic factors.
AB  - BACKGROUND: Tubular carcinoma (TC) of the breast has a very favourable prognosis.
      The role for axillary staging in small TC was questioned. This study investigated
      the frequency of axillary metastases and prognostic factors in pure TC of the
      breast. It involved a retrospective review of prospectively collected data.
      METHODS: A consecutive series of patients presenting to The Strathfield Breast
      Centre (TSBC) between 1988 and 2011 were reviewed. Only pure TC was included.
      Information collected included demographics, surgery, pathology, adjuvant therapy
      and survival. RESULTS: Pure TC accounted for 146 out of 6110 cases of operable
      breast cancer. Ninety-five per cent were node negative (micrometastases and
      isolated tumour cells excluded). Ninety-eight per cent of those with known
      oestrogen receptor status were oestrogen receptor positive. Median tumour size
      was 10 mm (range 1-52 mm). Ten-year survival was 97%. Twelve per cent of patients
      had more than one tumour (either ipsilateral or contralateral). Eight patients
      had recurrent disease. All were node negative. Three of these patients died of
      their disease. CONCLUSION: Axillary metastases are uncommon in pure TC. Recurrent
      disease is not readily predicted by tumour size or node status.

PMID- 25060385
TI  - Multiple and atypical opportunistic infections in a HIV patient with Toxoplasma
      myocarditis.
AB  - Opportunistic infections cause significant morbidity and mortality in patients
      infected with the human immunodeficiency virus (HIV). Multiple opportunistic
      infections can occur in a patient in the setting of severe immunodeficiency and
      can have atypical clinicoradiological presentation. Cardiac involvement has also
      been observed on autopsy in HIV-infected patients in the form of myocarditis,
      dilated cardiomyopathy, endocarditis, neoplasms, and drug-related cardiotoxicity.
      Mostly, the cardiac opportunistic infections are clinically asymptomatic, and
      sudden death due to these is extremely rare. We report a case of 44-year-old
      gentleman who presented with cough, pleuritic chest pain, and breathlessness and
      died of refractory shock due to myocarditis. At autopsy, he was found to have
      Toxoplasma myocarditis, Pneumocystis jirovecii pneumonia, and cytomegalovirus
      adrenalitis. 

PMID- 25060386
TI  - Human cardiac fibroblast extracellular matrix remodeling: dual effects of tissue
      inhibitor of metalloproteinase-2.
AB  - OBJECTIVE: Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous
      inhibitor of matrix metalloproteinases (MMPs) that attenuates maladaptive cardiac
      remodeling in ischemic heart failure. We examined the effects of TIMP-2 on human
      cardiac fibroblast activation and extracellular matrix (ECM) remodeling. METHODS:
      Human cardiac fibroblasts within a three-dimensional collagen matrix were
      assessed for phenotype conversion, ECM architecture and key molecular regulators
      of ECM remodeling after differential exposure to TIMP-2 and Ala+TIMP-2 (a
      modified TIMP-2 analogue devoid of MMP inhibitory activity). RESULTS: TIMP-2
      induced opposite effects on human cardiac fibroblast activation and ECM
      remodeling depending on concentration. TIMP-2 activated fibroblasts into
      contractile myofibroblasts that remodeled ECM. At higher concentrations (>10 nM),
      TIMP-2 inhibited fibroblast activation and prevented ECM remodeling. As compared
      to profibrotic cytokine transforming growth factor (TGF)-beta1, TIMP-2 activated
      fibroblasts and remodeled ECM without a net accumulation of matrix elements. TIMP
      2 increased total protease activity as compared to TGF-beta1. Ala+TIMP-2 exposure
      revealed that the actions of TIMP-2 on cardiac fibroblast activation are
      independent of its effects on MMP inhibition. In the presence of GM6001, a broad
      spectrum MMP inhibitor, TIMP-2-mediated ECM contraction was completely abolished,
      indicating that TIMP-2-mediated fibroblast activation is MMP dependent.
      CONCLUSION: TIMP-2 functions in a contextual fashion such that the effect on
      cardiac fibroblasts depends on the tissue microenvironment. These observations
      highlight potential clinical challenges in using TIMP-2 as a therapeutic strategy
      to attenuate postinjury cardiac remodeling.

PMID- 25060387
TI  - Thrombotic complications associated with transcatheter aortic valve implantation:
      the role of Kounis hypersensitivity-associated thrombotic syndrome.

PMID- 25060388
TI  - New sensitive detection method for lectin hemagglutination using microscopy.
AB  - The blood group system AB0 is determined by the composition of terminal
      oligosaccharides on red blood cells. Thanks to this structural feature, these
      groups can be recognized by saccharide-recognizing compounds. Lectins are
      proteins that are able to reversibly bind saccharide structures. They generally
      occur as multimers and are known as hemagglutination agents. Hemagglutination is
      a process in which blood cells are cross-linked via multivalent molecules. Apart
      from lectins, hemagglutination can also be caused by antibodies or viruses. A
      hemagglutination assay is commonly used for the detection of multivalent
      molecules that recognize blood cells, in order to search for their sugar
      specificity. It is traditionally performed on a microtiter plate, where the
      lectin solution is serially diluted and the lowest concentration of lectin
      causing agglutination is detected. This experimental set-up is utilized further
      for testing lectin specificity via a hemagglutination inhibition assay. We have
      developed a new way of detecting hemagglutination using microscopy, which was
      tested on purified lectins as well as cell lysates. Hemagglutination was
      performed on a microscope slide directly and detected using a microscope.
      Comparison with the standard hemagglutination assay using microtiter plates
      revealed that microscopic approach is faster and more robust and allows fast
      determination of lectin activities immediately in bacterial cytosols.

PMID- 25060390
TI  - The interaction of CuInS2 /ZnS/TGA quantum dots with tyrosine kinase inhibitor
      and its application.
AB  - The interactions between thioglycolic acid-capped-CuInS2 /ZnS quantum dots
      (CuInS2 /ZnS/TGA QDs) and tyrosine kinase inhibitor (TKI) were investigated using
      fluorescence, ultraviolet-visible spectrometry and Fourier transform infrared
      spectrometry. The results indicated that the fluorescence intensity of CuInS2
      /ZnS/TGA could be quenched by imatinib, dasatinib, nilotinib, gefitinib and
      erlotinib, which hinted that CuInS2 /ZnS/TGA QDs could be used in the detection
      of TKI in active pharmaceutical ingredients (API). Calibration curves showed good
      linear correlation and low detection limits. The average recovery was between 98
      and 102%. Moreover, the nature of the fluorescence quenching mechanism of CuInS2
      /ZnS/TGA QDs by TKI was discussed. A ground state complex was formed by hydrogen
      bonding between the carboxyl group of CuInS2 /ZnS/TGA QDs and the amino group of
      TKI. This led to an increase in non-radiative transition and fluorescence
      quenching of CuInS2 /ZnS/TGA QDs.

PMID- 25060389
TI  - Association of common genetic variants with diabetes and metabolic syndrome
      related traits in the Arizona Insulin Resistance registry: a focus on Mexican
      American families in the Southwest.
AB  - BACKGROUND/AIMS: The increased occurrence of type 2 diabetes and its clinical
      correlates is a global public health issue, and there are continued efforts to
      find its genetic determinant across ethnically diverse populations. The aims of
      this study were to determine the heritability of diabetes and metabolic syndrome
      phenotypes in the Arizona Insulin Resistance (AIR) registry and to perform an
      association analysis of common single nucleotide polymorphisms (SNPs) identified
      by GWAS with these traits. All study participants were Mexican Americans from the
      AIR registry. METHODS: Metabolic, anthropometric, demographic and medical history
      information was obtained on the 667 individuals enrolled in the registry.
      RESULTS: The heritability estimates were moderate to high in magnitude and
      significant, indicating that the AIR registry is well suited for the
      identification of genetic factors contributing to diabetes and the metabolic
      syndrome. From the 30 GWAS genes selected (some genes were represented by
      multiple SNPs), 20 SNPs exhibited associations with one or more of the diabetes
      related traits with nominal significance (p <= 0.05). In addition, 25 SNPs were
      nominally significantly associated with one or more of the metabolic phenotypes
      tested (p <= 0.05). Most notably, 5 SNPs from 5 genes [body mass index (BMI), hip
      circumference: rs3751812/FTO; fasting plasma glucose, hemoglobin A1c:
      rs4607517/GCK; very-low-density lipoprotein: rs10830963/MTNR1B; BMI:
      rs13266634/SLC30A8, and total cholesterol, low-density lipoprotein:
      rs7578597/THADA] were significantly associated with obesity, glycemic, and lipid
      phenotypes when using the multiple testing significance threshold of 0.0015.
      CONCLUSION: These findings extend previous work on Mexican Americans to suggest
      that metabolic disease is strongly influenced by genetic background in this high
      risk population.

PMID- 25060391
TI  - Frequency of dosage prescribing medication errors associated with manual
      prescriptions for very preterm infants.
AB  - WHAT IS KNOWN AND OBJECTIVE: The risk of dosage Prescription Medication Error
      (PME) among manually written prescriptions within 'mixed' prescribing system
      (computerized physician order entry (CPOE) + manual prescriptions) has not been
      previously assessed in neonatology. This study aimed to evaluate the rate of
      dosage PME related to manual prescriptions in the high-risk population of very
      preterm infants (GA < 33 weeks) in a mixed prescription system. METHODS: The
      study was based on a retrospective review of a random sample of manual daily
      prescriptions in two neonatal intensive care units (NICU) A and B, located in
      different French University hospitals (Dijon and La Reunion island). Daily
      prescription was defined as the set of all drugs manually prescribed on a single
      day for one patient. Dosage error was defined as a deviation of at least +/-10%
      from the weight-appropriate recommended dose. RESULTS AND DISCUSSION: The
      analyses were based on the assessment of 676 manually prescribed drugs from NICU
      A (58 different drugs from 93 newborns and 240 daily prescriptions) and 354
      manually prescribed drugs from NICU B (73 different drugs from 131 newborns and
      241 daily prescriptions). The dosage error rate per 100 manually prescribed drugs
      was similar in both NICU: 3.8% (95% CI: 2.5-5.6%) in NICU A and 3.1% (95% CI: 1.6
      5.5%) in NICU B (P = 0.54). Among all the 37 identified dosage errors, the over
      dosing was almost as frequent as the under-dosing (17 and 20 errors,
      respectively). Potentially severe dosage errors occurred in a total of seven drug
      prescriptions. None of the dosage PME was recorded in the corresponding medical
      files and information on clinical outcome was not sufficient to identify clinical
      conditions related to dosage PME. Overall, 46.8% of manually prescribed drugs
      were off label or unlicensed, with no significant differences between
      prescriptions with or without dosage error. The risk of a dosage PME increased
      significantly if the drug was included in the CPOE system but was manually
      prescribed (OR = 3.3; 95% CI: 1.6-7.0, P < 0.001). WHAT IS NEW AND CONCLUSION:
      The presence of dosage PME in the manual prescriptions written within mixed
      prescription systems suggests that manual prescriptions should be totally avoided
      in neonatal units.

PMID- 25060392
TI  - Dutch evidence-based guidelines for amputation and prosthetics of the lower
      extremity: Amputation surgery and postoperative management. Part 1.
AB  - BACKGROUND: Surgeons still use a range of criteria to determine whether
      amputation is indicated. In addition, there is considerable debate regarding
      immediate postoperative management, especially concerning the use of
      'immediate/delayed fitting' versus conservative elastic bandaging. OBJECTIVES: To
      produce an evidence-based guideline for the amputation and prosthetics of the
      lower extremities. This guideline provides recommendations in support of daily
      practice and is based on the results of scientific research and further
      discussions focussed on establishing good medical practice. Part 1 focuses on
      amputation surgery and postoperative management. STUDY DESIGN: Systematic
      literature design. METHODS: Literature search in five databases. Quality
      assessment on the basis of evidence-based guideline development. RESULTS: An
      evidence-based multidisciplinary guideline on amputation and prosthetics of the
      lower extremity. CONCLUSION: The best care (in general) for patients undergoing
      amputation of a lower extremity is presented and discussed. This part of the
      guideline provides recommendations for diagnosis, referral, assessment, and
      undergoing amputation of a lower extremity and can be used to provide patient
      information. CLINICAL RELEVANCE: This guideline provides recommendations in
      support of daily practice and is based on the results of scientific research and
      further discussions focussed on establishing good medical practice.

PMID- 25060393
TI  - Dutch evidence-based guidelines for amputation and prosthetics of the lower
      extremity: Rehabilitation process and prosthetics. Part 2.
AB  - BACKGROUND: A structured, multidisciplinary approach in the rehabilitation
      process after amputation is needed that includes a greater focus on the
      involvement of both (para)medics and prosthetists. There is considerable
      variation in prosthetic prescription concerning the moment of initial prosthesis
      fitting and the use of replacement parts. OBJECTIVES: To produce an evidence
      based guideline for the amputation and prosthetics of the lower extremities. This
      guideline provides recommendations in support of daily practice and is based on
      the results of scientific research and further discussions focussed on
      establishing good medical practice. Part 2 focuses on rehabilitation process and
      prosthetics. STUDY DESIGN: Systematic literature design. METHODS: Literature
      search in five databases and quality assessment on the basis of evidence-based
      guideline development. RESULTS: An evidence-based multidisciplinary guideline on
      amputation and prosthetics of the lower extremity. CONCLUSION: The best care (in
      general) for patients undergoing amputation of a lower extremity is presented and
      discussed. This part of the guideline provides recommendations for treatment and
      reintegration of patients undergoing amputation of a lower extremity and can be
      used to provide patient information. CLINICAL RELEVANCE: This guideline provides
      recommendations in support of daily practice and is based on the results of
      scientific research and further discussions focussed on establishing good medical
      practice.

PMID- 25060394
TI  - Evaluation of quality of life and walking ability among amputated patients and
      those who refused to undergo amputation following infection of total knee
      arthroplasty: Small case series.
AB  - BACKGROUND: Patients who undergo transfemoral amputation after infection of a
      total knee arthroplasty do not have good functional outcomes and have major
      difficulty walking. OBJECTIVES: To evaluate the quality of life and walking
      ability among patients who underwent amputation and among those who refused to
      undergo amputation following infection of a total knee arthroplasty. STUDY
      DESIGN: Retrospective case series. METHODS: Patients who received an indication
      for amputation following an infection of a total knee arthroplasty were evaluated
      retrospectively. The patients were divided between those who accepted the
      amputation procedure and those who refused amputation (four amputee vs four non
      amputees). Walking ability and quality of life were evaluated using the Short
      Form-36 questionnaire. RESULTS: The average physical health was 27.4 for the
      amputees and 31.3 for the non-amputees. The average mental health was 49.9 for
      the amputees and 47.1 for the non-amputees. In relation to walking ability, only
      one (25%) of the amputees was able to walk, as opposed to 100% in the non-amputee
      groups. CONCLUSION: Twenty-five percent of the amputee patients continued to be
      able to walk. The functional outcome of non-amputee patients was better, with
      100% being able to walk, though with limitations. CLINICAL RELEVANCE: This is the
      first study evaluating patients who refused the amputation procedure and remained
      with the spacer. Despite the fact that this option is not recommended by the
      medical community, we believe that these data are useful when discussing, with a
      patient, quality of life after amputation.

PMID- 25060395
TI  - Rocker outsole shoe is not a threat to postural stability in patients with
      diabetic neuropathy.
AB  - BACKGROUND: Rocker outsole shoes are commonly prescribed to patients with
      diabetic neuropathy to offload a particular area of the foot sole, thereby
      decreasing the risk of foot ulceration. Contrary to this, some evidence has
      reported a postural destabilising effect of these shoes in healthy adults.
      OBJECTIVE: To explore the postural stability of patients with diabetic neuropathy
      who wear a rocker outsole shoe. STUDY DESIGN: Quasi-experimental. METHOD: In
      total, 17 patients with diabetic neuropathy (aged 49.29 +/- 7.48 years; 7 female,
      10 males) participated in this study. A Motor Control Test measuring centre of
      force displacement, response strength scale and response latency in medium and
      large perturbations was conducted using the EquiTest system to evaluate postural
      stability while wearing a baseline shoe (without a rocker outsole) or a rocker
      outsole shoe (with a toe-only rocker sole). RESULTS: No significant difference
      was observed between the shoe conditions in centre of force displacement and
      response latency of the participants (p > 0.05). The results indicated a
      significant increase in the response strength scale of participants by the rocker
      outsole, for medium forward and backward and large forward perturbations (p =
      0.014, p = 0.001 and p = 0.027, respectively). CONCLUSION: When the immediate
      effect is a concern, the rocker outsole shoe did not negatively affect postural
      stability in patients with diabetic neuropathy. CLINICAL RELEVANCE: This article
      will provide objective evidence about the effect of rocker outsole on postural
      balance in diabetic patients. In prescription of rocker outsole to prevent
      plantar ulceration of diabetic foot, immediate postural destabilising is not a
      concern.

PMID- 25060396
TI  - Contribution of transcription factor, SP1, to the promotion of HB-EGF expression
      in defense mechanism against the treatment of irinotecan in ovarian clear cell
      carcinoma.
AB  - Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other
      ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth
      factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of
      this study were to validate the efficacy of HB-EGF-targeted therapy for OCCC and
      to identify the transcription factor that contributed to the induction of HB-EGF
      by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and
      an increase of HB-EGF was induced by SN38 which had only antitumor effect among
      conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross
      reacting material 197 (CRM197), led to a synergistic increase in the number of
      apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5'
      deletion promoter constructs identified a GC-rich element between -125 and -178
      (the distal transcription start site was denoted +1) as a cis-regulatory region,
      and the treatment of SN38 induced luciferase activity in this region. An in
      silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the
      cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability
      assays showed that the transfection of a small interfering RNA targeting SP1
      suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced
      sensitivity of SN38. Taken together, these results indicate that induction of HB
      EGF expression contributed to defense mechanism against treatment of SN38 through
      the transcriptional activity of SP1 in OCCC cells. 

PMID- 25060397
TI  - [Indications for laparoscopic treatment of large incisional hernias].
AB  - Hernia surgeons and patients have learned to appreciate the advantages of
      minimally invasive laparoscopic procedures. After overcoming the early learning
      curve phase, smaller wound surface areas, shorter operation times and briefer
      hospital stays have become routine. Severe surgery-related complications are
      rare. Patients with poor risk profiles (e.g. age >70 years, BMI >30 and nicotine
      consumption) profit especially from these advantages. This positive picture is
      clouded, however, by the need for an intraperitoneal mesh and specifically by the
      unchanged recurrence rate. The latter is not significantly lowered even by
      laparoscopic intraperitoneal on-lay mesh (laparoscopic IPOM) procedures. The
      current literature shows that irrespective of surgical technique, e.g.
      retromuscular mesh or laparoscopic IPOM, the risk profile and size of the hernia
      defect are independent factors that determine the prognosis for recurrence. While
      a cure of incisional hernia is no longer the only goal, the new indication
      scenario has two main goals: (a) for young patients at low risk or in patients
      for whom functional and morphological reconstruction of the abdominal wall are of
      primary importance, an open retromuscular mesh procedure is indicated (despite
      the higher morbidity) and (b) for older patients and chiefly for patients with a
      complex risk profile for whom treatment of the ventral hernia symptoms is
      paramount, laparoscopic procedures are indicated (due to the lower morbidity).
      This algorithm assumes that the treating surgeons have the requisite expertise
      and is discussed using the examples of four complex case reports.

PMID- 25060398
TI  - [Long-term comparison of quality of life after total and proximal gastrectomy].

PMID- 25060399
TI  - Progression of liver disease in non-alcoholic fatty liver disease: a prospective
      clinicopathological follow-up study.
AB  - OBJECTIVE: To perform a follow-up study on non-alcoholic fatty liver disease
      (NAFLD) patients in our previous study using paired liver biopsy. METHODS:
      Patients who were included in our previous study on NAFLD and agreed to receive a
      repeat liver biopsy were included in the study. Their clinical characteristics,
      laboratory examination results and histological analysis on the repeat liver
      biopsied specimens were prospectively collected and compared with those in the
      previous study. RESULTS: Data from 35 patients (mean age 47.5 +/- 10.9 years,
      male 40.0%) were analyzed. The mean interval between the liver biopsies was 6.4
      +/- 0.8 years. NAFLD activity score (NAS) worsened in 13, remained unchanged in 9
      and ameliorated in 13. Fibrosis worsened in 18 and remained unchanged in 17. Two
      patients who were confirmed with cirrhosis at baseline developed decompensated
      cirrhosis. On multivariate analysis, elevated serum aspartate aminotransferase
      (AST) (odds ratio [OR] 10.74, 95% confidence interval [CI] 1.00-115.86, P =
      0.050) and gamma-glutamyl transpeptidase (gamma-GT) (OR 16.10, 95% CI 1.30
      198.90, P = 0.030) at follow-up were associated with worsened NAS. Patients with
      borderline NASH at baseline were more likely to have worsened NAS at follow-up
      than those with definite NASH (OR 12.67, 95% CI 2.29-70.02, P = 0.004). However,
      both groups had a similar likelihood of having worsened fibrosis at follow-up. No
      plausible factors were found to be associated with worsened fibrosis.
      CONCLUSIONS: NAFLD patients with persistently elevated serum AST and gamma-GT
      levels during follow-up should be suspected of having worsened NAS. NASH patients
      can have significant disease progression over a relatively short period of time
      and fibrosis might be irreversible without specific interventions.

PMID- 25060400
TI  - Blood lead, cadmium and mercury among children from urban, industrial and rural
      areas of Fez Boulemane Region (Morocco): relevant factors and early renal
      effects.
AB  - OBJECTIVES: To describe blood lead (Pb-B), cadmium (Cd-B) and mercury (Hg-B)
      levels in children living in urban, industrial and rural areas in Fez city (north
      of Morocco) and to identify the determinants and some renal effects of exposure.
      MATERIAL AND METHODS: The study was conducted from June 2007 to January 2008 in
      209 school children (113 girls, 96 boys), aged 6-12 years, from urban, industrial
      and rural areas in Fez city. Interview and questionnaires data were obtained.
      Blood and urinary samples were analyzed. RESULTS: The mean of blood lead levels
      (Pb-B) in our population was 55.53 MUg/l (range: 7.5-231.1 MUg/l). Children from
      the urban area had higher blood lead levels (BLLs) mean (82.36 MUg/l) than
      children from industrial and rural areas (48.23 and 35.99 MUg/l, respectively);
      with no significant difference between boys and girls. BLLs were associated with
      traffic intensity, passive smoking and infancy in the urban area. The mean of
      blood cadmium levels (BCLs) was 0.22 MUg/l (range: 0.06-0.68 MUg/l), with no
      difference between various areas. Rural boys had higher BCLs mean than rural
      girls, but no gender influence was noticed in the other areas. BCLs were
      associated with the number of cigarettes smoked at children's homes. The blood
      mercury levels (BMLs) mean was 0.49 MUg/l (range: 0.01-5.31 MUg/l). The BMLs mean
      was higher in urban and industrial areas than in the rural area with no gender
      related difference. BMLs were associated with amalgam fillings and infancy in the
      urban area. About 8% of the children had BLLs >= 100 MUg/l particularly in the
      urban area, microalbuminuria and a decrease in height were noticed in girls from
      the inner city of Fez and that can be related to high BLLs (89.45 MUg/l).
      CONCLUSIONS: There is a need to control and regulate potential sources of
      contamination by these trace elements in children; particularly for lead.

PMID- 25060401
TI  - A new method of determination of phases and symmetry in stand-to-sit-to-stand
      movement.
AB  - OBJECTIVES: Determination of the phases in a stand-to-sit-to-stand task based on
      a derivative of the parameter with the lowest variance calculated based on the
      modified symmetry index. MATERIAL AND METHODS: The study group comprised 11
      healthy women and 11 healthy men from the University of Physical Education in
      Warsaw. The examination of the kinematic and kinetic parameters of sitting down
      and standing up from a chair was carried out using the Vicon Mx system and
      Kistler force platforms. RESULTS: The modified symmetry index was employed to
      select the parameters used to choose those with the lowest variance.
      Consequently, the phases in a stand-to-sit-to-stand task were determined.
      CONCLUSIONS: It was demonstrated that the task of sitting down is a reverse task
      with respect to standing up in terms of the symmetry of the parameters analyzed.

PMID- 25060402
TI  - Occupational concerns associated with regular use of microscope.
AB  - OBJECTIVES: Microscope work can be strenuous both to the visual system and the
      musculoskeletal system. Lack of awareness or indifference towards health issues
      may result in microscope users becoming victim to many occupational hazards. Our
      objective was to understand the occupational problems associated with regular use
      of microscope, awareness regarding the hazards, attitude and practice of
      microscope users towards the problems and preventive strategies. MATERIAL AND
      METHODS: a questionnaire based survey done on 50 professionals and technicians
      who used microscope regularly in pathology, microbiology, hematology and cytology
      laboratories. RESULTS: Sixty two percent of subjects declared that they were
      suffering from musculoskeletal problems, most common locations being neck and
      back. Maximum prevalence of musculoskeletal problems was noted in those using
      microscope for 11-15 years and for more than 30 h/week. Sixty two percent of
      subjects were aware of workplace ergonomics. Fifty six percent of microscope
      users took regular short breaks for stretching exercises and 58% took visual
      breaks every 15-30 min in between microscope use sessions. As many as 94%
      subjects reported some form of visual problem. Fourty four percent of microscope
      users felt stressed with long working hours on microscope. CONCLUSIONS: The most
      common occupational concerns of microscope users were musculoskeletal problems of
      neck and back regions, eye fatigue, aggravation of ametropia, headache, stress
      due to long working hours and anxiety during or after microscope use. There is an
      immediate need for increasing awareness about the various occupational hazards
      and their irreversible effects to prevent them.

PMID- 25060404
TI  - Let me please introduce you to the contents of the July-August number of our
      bimonthly. Introduction.

PMID- 25060403
TI  - Acute methoxetamine and amphetamine poisoning with fatal outcome: a case report.
AB  - Methoxetamine (MXE) is a psychoactive substance distributed mostly via the
      Internet and is not liable to legal regulation in Poland. MXE has a toxicity
      profile similar to that of ketamine but longer-lasting effects. The paper
      describes a case of acute poisoning that resulted from recreational use of MXE
      and amphetamine and ended in death. In mid-July 2012, a 31-year old man was
      admitted to the clinical toxicology unit in Gdansk because of poisoning with an
      unknown psychoactive substance. The patient was transported to the emergency
      department (ED) at 5:15 a.m. in a very poor general condition, in a deep coma,
      with acute respiratory failure, hyperthermia (> 39 degrees C) and generalized
      seizures. Laboratory tests showed marked leukocytosis, signs of massive
      rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite
      intensive therapy, the patient died 4 weeks after the poisoning in the course of
      multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and
      urine samples collected on the poisoning day at 1:40 p.m. confirmed that
      amphetamine and MXE had been taken earlier that day. Concentration of amphetamine
      in the serum (0.06 MUg/ml) was within the non-toxic range, while MXE (0.32
      MUg/ml) was within the toxic range of concentrations. Amphetamine was also
      detected in the patient's hair, which suggested a possibility of its use within
      the last dozen weeks or so. The serious clinical course of intoxication and co
      existence of amphetamine and MXE in the patient's blood and urine suggest the
      possibility of adverse interactions between them. 

PMID- 25060405
TI  - Characteristics and behaviour of liposomes when incubated with natural bile salt
      extract: implications for their use as oral drug delivery systems.
AB  - The use of liposomes for oral administration of drugs and for food applications
      is based on their ability to preserve entrapped substances and to increase their
      bioavailability. Bile salts are one of the agents that affect the liposome
      structure during intestinal digestion and the main reported studies on
      liposome/bile salt systems used only one bile salt. The aim of this work is to
      characterise the interaction of liposomes with a natural bile salt extract (BSE)
      at physiological pH and temperature. Three types of liposomes (fluid, gel-state
      and liquid-ordered bilayers) were studied. Phase diagrams were obtained and a
      very different behaviour was found. Fluid bilayers were completely permeable to
      an entrapped dye with partial or complete disruption of vesicles (final size 10
      nm). Gel-state bilayers released their content but BSE led to the formation of
      large mixed structures (2000 nm). Liquid-ordered bilayers formed mixed vesicles
      (1000 nm) and, surprisingly, retained a high percentage of their aqueous content
      (about 50%). As a consequence, each type of liposome offers singular features to
      be used in oral applications due to their specific interaction with bile salts. 

PMID- 25060407
TI  - Personalised medicine: the cognitive side of patients.
AB  - BACKGROUND: Although the fashion for the "personalised" or "stratified" approach
      to medicine is valuable in exploiting the omic signatures of the individual
      patient, too little attention has been paid to the influence of psychological and
      cognitive factors in the care process. The aim of this paper is to highlight the
      importance of those individual psycho-cognitive components in affecting how
      people act to prevent, cope and react to illness, decide about different
      therapeutic options, interact with health care providers, and adhere to
      treatment. METHODS: We reviewed the medical and psychological literature about
      the effect of cognitive and psychological dimensions on treatment efficacy, on
      patients' global satisfaction, and on treatment compliance. RESULTS:
      Psychological dimensions have been proved to impact on treatment efficacy, on
      patients' global satisfaction, and on compliance to treatment. However, there are
      substantial individual differences among patients; therefore, it is important
      that physicians recognise how to apply these general recommendations to each
      individual patient, alongside the omic information emerging from the molecular
      diagnostic laboratory. CONCLUSION: The exam of the current literature allows one
      to derive several strategies which can help health professionals to improve the
      patients' understanding of their disease and involvement in the whole care
      process.

PMID- 25060406
TI  - Patient Satisfaction with Fentanyl Sublingual Spray in Opioid-Tolerant Patients
      with Breakthrough Cancer Pain.
AB  - OBJECTIVES: Breakthrough cancer pain (BTCP) is associated with decreased
      satisfaction with around-the-clock opioid therapy. This analysis examined patient
      satisfaction with fentanyl sublingual spray for BTCP during the open-label
      titration period of a randomized, placebo-controlled study. METHODS: Opioid
      tolerant patients with 1 to 4 daily BTCP episodes were included. During a 26-day,
      open-label titration phase, a successful dose (100 to 1600 mcg) of fentanyl
      sublingual spray was established that provided effective analgesia for 2
      consecutive BTCP episodes with tolerable side effects. The Treatment Satisfaction
      Questionnaire for Medication (TSQM) was administered at baseline to assess
      satisfaction with previous BTCP medication and at the end of the titration to
      assess satisfaction with fentanyl sublingual spray. RESULTS: Of 130 enrolled
      patients, 115 (88.5%) had a TSQM measure at baseline and at the end of their
      titration period. Scores on all 4 TSQM domains increased from baseline to end of
      the titration, with mean (standard error [SE]) improvements of 22.3 (2.3) for
      effectiveness, 7.7 (3.2) for side effects, 6.8 (2.2) for convenience, and 12.9
      (2.8) for global satisfaction (P < 0.05 for all). Satisfaction with symptom
      relief (26.1% to 77.4%) and onset of action (21.7% to 82.6%) also improved from
      baseline to end of titration. At least one adverse event (AE) was reported by 78
      patients (60.0%). The most common AEs considered possibly or probably related to
      study medication were dizziness, somnolence, and nausea (n = 10 [7.7%] each).
      DISCUSSION: These data indicate markedly improved satisfaction among patients
      receiving fentanyl sublingual spray relative to previous BTCP medications.

PMID- 25060409
TI  - Environmental influence on cyanobacteria abundance and microcystin toxin
      production in a shallow temperate lake.
AB  - The increasing frequency of harmful cyanobacterial blooms in freshwater systems
      is a commonly recognized problem due to detrimental effects on water quality.
      Vancouver Lake, a shallow, tidally influenced lake in the flood plain of the
      Columbia River within the city of Vancouver, WA, USA, has experienced numerous
      summertime cyanobacterial blooms, dominated by Aphanizomenon sp. and Anabaena sp.
      Cyanobacteria abundance and toxin (microcystin) levels have been monitored in
      this popular urban lake for several years; however, no previous studies have
      identified which cyanobacteria species produce toxins, nor analyzed how changes
      in environmental variables contribute to the fluctuations in toxic cyanobacteria
      populations. We used a suite of molecular techniques to analyze water samples
      from Vancouver Lake over two summer bloom cycles (2009 and 2010). Both
      intracellular and extracellular microcystin concentrations were measured using an
      ELISA kit. Intracellular microcystin concentrations exceeded WHO guidelines for
      recreational waters several times throughout the sampling period. PCR results
      demonstrated that Microcystis sp. was the sole microcystin-producing
      cyanobacteria species present in Vancouver Lake, although Microcystis sp. was
      rarely detected in microscopical counts. qPCR results indicated that the majority
      of the Microcystis sp. population contained the toxin-producing gene (mcyE),
      although Microcystis sp. abundance rarely exceeded 1 percent of overall
      cyanobacteria abundance. Non-metric multidimensional scaling (NMDS) revealed that
      PO4-P was the main environmental variable influencing the abundance of toxic and
      non-toxic cyanobacteria, as well as intracellular microcystin concentrations. Our
      study underscores the importance of using molecular genetic techniques, in
      addition to traditional microscopy, to assess the importance of less conspicuous
      species in the dynamics of harmful algal blooms. 

PMID- 25060410
TI  - Long working hours and pregnancy complications: women physicians survey in Japan.
AB  - BACKGROUND: Previous studies have investigated the impact of occupational risk
      factors on health outcomes among physicians. However, few studies have
      investigated the effects on pregnancy outcomes among physicians. In this study,
      we examined the association between working hours during pregnancy and pregnancy
      complications among physicians. METHODS: A cross-sectional study was based on a
      survey conducted in 2009-2011 of 1,684 alumnae (mean age, 44 +/- 8 years) who had
      graduated from 13 private medical schools in Japan. Data on threatened abortion
      (TA), preterm birth (PTB), and the number of working hours during the first
      trimester of pregnancy were obtained via retrospective assessments. RESULTS: Of
      the 939 physicians with a first pregnancy, 15% experienced TA and 12% experienced
      PTB. Women who experienced TA (mean weekly working hours: 62 h vs. 50 h, P <
      .0001) or PTB (62 h vs. 50 h, P < .0001) had longer weekly working hours during
      the first trimester than did those without pregnancy complications. Compared with
      women who worked 40 hours or less per week, women who worked 71 hours or more per
      week had a three-fold higher risk of experiencing TA (95% confidence interval
      (CI): 1.7-6.0) even after adjusting for medical specialty, maternal age, and
      current household income. The risk of experiencing PTB was 2.5 times higher (95%
      CI:1.2-5.2) in women who worked 51-70 hours and 4.2 times higher (95% CI: 1.9
      9.2) in women who worked 71 hours or more even after adjusting for specialty,
      maternal age, and current household income. The trend in the P statistic
      reflecting the effect of the quartile of hours worked per week (40 hours, 41-50
      hours, 51-70 hours, >= 71 hours) on TA or PTB was 0.0001 in the multivariate
      logistic regression models. CONCLUSION: These results suggest that working long
      hours during the first trimester of pregnancy is associated with TA and PTB.

PMID- 25060411
TI  - Setting the table for change.

PMID- 25060412
TI  - Improving the growth of Rubrivivax gelatinosus cultivated in sewage environment.
AB  - Rubrivivax gelatinosus cultivated in wastewater environment can combine the
      biomass resource recycling for generating chemicals with sewage purification.
      However, low biomass accumulation restricts the exertion of this advantage. Thus,
      this paper investigated Fe(3+) advancement for biomass production in starch
      wastewater under light-anaerobic condition. Results showed that addition of
      Fe(3+) was successful in enhancing biomass production, which certainly improved
      the feasibility of biomass recycling in R. gelatinosus starch wastewater
      treatment. With optimal Fe(3+) dosage (20 mg/L), biomass production reached 4,060
      mg/L, which was 1.63 times that of control group. Amylase activity was improved
      by 48 %. Both COD removal and starch removal reached 90 %. Hydraulic retention
      time was shortened by 25 %. Proper Fe(3+) dosage enhanced biomass production, but
      excess Fe(3+) was harmful for biomass accumulation. 

PMID- 25060413
TI  - Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9
      antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two
      weeks dosing from phase 2 trials).
AB  - Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease,
      with limited treatment options. This analysis evaluated the effect of a
      monoclonal antibody to proprotein convertase subtilisin/kexin 9, alirocumab 150
      mg every 2 weeks (Q2W), on Lp(a) levels in pooled data from 3 double-blind,
      randomized, placebo-controlled, phase 2 studies of 8 or 12 weeks' duration
      conducted in patients with hypercholesterolemia on background lipid-lowering
      therapy (NCT01266876, NCT01288469, and NCT01288443). Data were available for 102
      of 108 patients who received alirocumab 150 mg Q2W and 74 of 77 patients who
      received placebo. Alirocumab resulted in a significant reduction in Lp(a) from
      baseline compared with placebo (-30.3% vs -0.3%, p <0.0001). Median percentage
      Lp(a) reductions in the alirocumab group were of a similar magnitude across a
      range of baseline Lp(a) levels, resulting in greater absolute reductions in Lp(a)
      in patients with higher baseline levels. Regression analysis indicated that <5%
      of the variance in the reduction of Lp(a) was explained by the effect of
      alirocumab on low-density lipoprotein cholesterol. In conclusion, pooled data
      from 3 phase 2 trials demonstrate substantive reduction in Lp(a) with alirocumab
      150 mg Q2W, including patients with baseline Lp(a) >50 mg/dl. Reductions in Lp(a)
      only weakly correlated with the magnitude of low-density lipoprotein cholesterol
      lowering. 

PMID- 25060414
TI  - Mineralocorticoid receptor antagonist use in hospitalized patients with heart
      failure, reduced ejection fraction, and diabetes mellitus (from the EVEREST
      Trial).
AB  - Despite the well-established benefits of mineralocorticoid receptor agonists
      (MRAs) in heart failure with reduced ejection fraction, safety concerns remain in
      patients with concomitant diabetes mellitus (DM) because of common renal and
      electrolyte abnormalities in this population. We analyzed all-cause mortality and
      composite cardiovascular mortality and HF hospitalization over a median 9.9
      months among 1,998 patients in the placebo arm of the Efficacy of Vasopressin
      Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial by DM
      status and discharge MRA use. Of the 750 patients with DM, 59.2% were receiving
      MRAs compared with 62.5% in the non-DM patients. DM patients not receiving MRAs
      were older, more likely to be men, with an ischemic heart failure etiology and
      slightly worse renal function compared with those receiving MRAs. After
      adjustment for baseline risk factors, among DM patients, MRA use was not
      associated with either mortality (hazard ratio [HR] 0.93; 95% confidence interval
      [CI] 0.75 to 1.15) or the composite end point (HR 0.94; 95% CI 0.80 to 1.10).
      Similar findings were seen in non-DM patients (mortality [HR 1.01; 95% CI 0.84 to
      1.22] or the composite end point [HR 0.98; 95% CI 0.85 to 1.13] [p >0.43 for DM
      interaction]). In conclusion, in-hospital initiation of MRA therapy was low (15%
      to 20%), and overall discharge MRA use was only 60% (with regional variation),
      regardless of DM status. There does not appear to be clear, clinically
      significant in-hospital hemodynamic or even renal differences between those on
      and off MRA. Discharge MRA use was not associated with postdischarge end points
      in patients hospitalized for worsening heart failure with reduced ejection
      fraction and co-morbid DM. DM does not appear to influence the effectiveness of
      MRA therapy. 

PMID- 25060415
TI  - Optimal blood pressure in patients with atrial fibrillation (from the AFFIRM
      Trial).
AB  - Many medications used to treat atrial fibrillation (AF) also reduce blood
      pressure (BP). The relation between BP and mortality is unclear in patients with
      AF. We performed a post hoc analysis of 3,947 participants from the Atrial
      Fibrillation Follow-Up Investigation of Rhythm Management trial. Systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) at baseline and follow-up were
      categorized by 10-mm Hg increments. The end points were all-cause mortality (ACM)
      and secondary outcome (combination of ACM, ventricular tachycardia and/or
      fibrillation, pulseless electrical activity, significant bradycardia, stroke,
      major bleeding, myocardial infarction, and pulmonary embolism). SBP and DBP
      followed a "U-shaped" curve with respect to primary and secondary outcomes after
      multivariate analysis. A nonlinear Cox proportional hazards model showed that the
      incidence of ACM was lowest at 140/78 mm Hg. Subgroup analyses revealed similar U
      shaped curves. There was an increased ACM observed with BP <110/60 mm Hg (hazard
      ratio 2.4, p <0.01, respectively, for SBP and DBP). In conclusion, in patients
      with AF, U-shaped relation existed between BP and ACM. These data suggest that
      the optimal BP target in patients with AF may be greater than the general
      population and that pharmacologic therapy to treat AF may be associated with ACM
      or adverse events if BP is reduced to <110/60 mm Hg. 

PMID- 25060416
TI  - Getting evidence-based pressure ulcer prevention into practice: a multi-faceted
      unit-tailored intervention in a hospital setting.
AB  - The aim of the study was to evaluate whether a multi-faceted, unit-tailored
      intervention using evidenced-based pressure ulcer prevention affects (i) the
      performance of pressure ulcer prevention, (ii) the prevalence of pressure ulcers
      and (iii) knowledge and attitudes concerning pressure ulcer prevention among
      registered and assistant nurses. A quasi-experimental, clustered pre- and post
      test design was used. Five units at a hospital setting were included. The
      intervention was based on the PARIHS framework and included a multi-professional
      team, training and repeated quality measurements. An established methodology was
      used to evaluate the prevalence and prevention of pressure ulcers. Nurses'
      knowledge and attitudes were evaluated using a validated questionnaire. A total
      of 506 patients were included, of whom 105 patients had a risk to develop
      pressure ulcer. More patients were provided pressure ulcer prevention care (P =
      0.001) and more prevention care was given to each patient (P = 0.021) after the
      intervention. Corresponding results were shown in the group of patients assessed
      as being at risk for developing pressure ulcers. Nurses' knowledge about pressure
      ulcer prevention increased (P < 0.001). Positive attitudes towards pressure ulcer
      prevention remained high between pre- and post-test surveys. This multi-faceted
      unit-tailored intervention affected pressure ulcer prevention. Facilitation and
      repeated quality measurement together with constructed feedback of results seemed
      to be the most important factor for pressure ulcer prevention. 

PMID- 25060417
TI  - Efficacy of diflunisal on autonomic dysfunction of late-onset familial amyloid
      polyneuropathy (TTR Val30Met) in a Japanese endemic area.
AB  - OBJECTIVE: To evaluate the long-term efficacy and safety of diflunisal in late
      onset familial amyloid polyneuropathy (FAP) in a Japanese endemic area. METHODS:
      Consecutive six FAP patients (mean age: 65.8 +/- 7.3 years) with a transthyretin
      (TTR) Val30Met mutation from an endemic area of late-onset FAP were prospectively
      recruited to an open label study with oral diflunisal (250 mg twice a day). We
      evaluated clinical symptoms, Kumamoto FAP score, modified body mass index (mBMI),
      Medical Research Council sum score, nerve conduction studies (NCS),
      electrocardiogram (ECG), ECG Holter monitor test, echocardiography, and
      (123)iodine-metaiodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy.
      RESULTS: One patient ceased to take diflunisal because of hematuria which was
      reversible. The other five patients were treated with diflunisal for 3-5 (4.4 +/-
      0.9 years) years. Autonomic symptoms (orthostatic hypotension and
      gastrointestinal symptoms) disappeared after treatment in two of the four
      patients with the symptoms. Delayed heart to mediastinum ratio on (123)I-MIBG
      imaging, a marker of cardiac postganglionic sympathetic nerve function, increased
      during the three-year treatment. mBMI was maintained through observation period.
      While, motor and sensory symptoms, Kumamoto FAP scores, and data on NCS gradually
      deteriorated. CONCLUSION: Diflunisal might be effective especially for autonomic
      dysfunction in late-onset FAP with a TTR Val30Met mutation.

PMID- 25060418
TI  - A dose-response study of thymosin beta4 for the treatment of acute stroke.
AB  - BACKGROUND: Thymosin beta4 (Tbeta4) is a 5K actin binding peptide. Tbeta4
      improves neurological outcome in a rat model of embolic stroke and research is
      now focused on optimizing its dose for clinical trials. The purpose of this study
      was to perform a dose-response study of Tbeta4 to determine the optimal dose of
      neurological improvement in a rat model of embolic stroke. METHODS: Male Wistar
      rats were subjected to embolic middle cerebral artery occlusion (MCAo). Rats were
      divided into 4 groups of 10 animals/group: control, 2, 12 and 18 mg/kg. Tbeta4
      was administered intraperitoneally 24h after MCAo and then every 3 days for 4
      additional doses in a randomized controlled fashion. Neurological tests were
      performed after MCAo and before treatment and up to 8 weeks after treatment. The
      rats were sacrificed 56 days after MCAo and lesion volumes measured. Generalized
      estimating equation was used to compare the treatment effect on long term
      functional recovery at day 56. A quartic regression model was used for an optimal
      dose determination. RESULTS: Tbeta4 significantly improved neurological outcome
      at dose of 2 and 12 mg/kg at day 14 and extended to day 56 (p-values <0.05). The
      higher dose of 18 mg/kg did not show significant improvement. The estimated
      optimal dose of 3.75 mg/kg would provide optimal neurological improvement.
      CONCLUSIONS: This study shown that Tbeta4 significantly improved the long term
      neurological functional recovery at day 56 after MCAo with an optimal dose of
      3.75 mg/kg. These results provide preclinical data for human clinical trials.

PMID- 25060419
TI  - Bilateral cytotoxic edema of the centrum semiovale in uremic encephalopathy.

PMID- 25060420
TI  - Treatment outcome in carpal tunnel syndrome: does distribution of sensory
      symptoms matter?
AB  - BACKGROUND: Patients with complaints of carpal tunnel syndrome (CTS) with signs
      and symptoms not exclusively confined to the median nerve territory, but
      otherwise fulfilling the clinical criteria may erroneously be withheld from
      therapy. METHODS: One hundred and twenty one patients who fulfilled the clinical
      criteria for the diagnosis of CTS with signs and symptoms restricted to the
      median nerve territory (group A) and 91 patients without this restriction (group
      B) were included in a prospective cohort study. All patients fulfilled
      electrodiagnostic criteria of CTS. Outcome was determined after 7 to 9 months by
      means of Symptom Severity Score (SSS) and Functional Status Score (FSS) according
      to Levine and a patient satisfaction questionnaire. RESULTS: Response rates were
      81.8% (group A) and 82.4% (group B). All patients in group B had sensory symptoms
      involving digit 5. There were no significant differences in improvement of SSS,
      FSS and patient satisfaction scores between groups after treatment. CONCLUSION:
      CTS patients with characteristic sensory signs and symptoms not exclusively
      restricted to the median nerve innervated area should be treated in the same
      manner as patients with CTS symptoms restricted to the median nerve innervated
      area and should therefore not be withheld from surgical treatment.

PMID- 25060421
TI  - A review of the management of elderly patients with non-small-cell lung cancer.
AB  - Most patients with non-small-cell lung cancer (NSCLC) are elderly but evidence to
      guide appropriate treatment decisions for this age group is generally scant.
      Careful evaluation of the elderly should be undertaken to ensure that treatment
      appropriate for the stage of the tumour is guided by patient characteristics and
      not by age. The Comprehensive Geriatric Assessment (CGA) remains the preferred
      option, but briefer tools may be appropriate to select patients for further
      evaluation. The predicted outcome should be used to guide management decisions
      together with a reappraisal of polypharmacy. Patient expectations should also be
      taken into account. Management recommendations are generally similar to those of
      general guidelines for the NSCLC population, although the risks of surgery and
      toxicity of chemotherapy and radiotherapy are often increased in the elderly
      compared with younger patients; therefore, patients should be closely scrutinised
      and subjected to a CGA to ensure suitability of the planned treatment. If surgery
      is indicated, then lobectomy is generally the preferred option, although limited
      resection may be more feasible for some. Radiotherapy with curative intent is an
      alternative, with stereotactic body radiotherapy the most likely preferred
      modality. Adjuvant chemotherapy is also an appropriate approach, whereas adjuvant
      radiotherapy is generally not recommended. Concurrent chemoradiotherapy should be
      considered for elderly patients with inoperable locally advanced disease and
      chemotherapy for advanced/metastatic disease. Efforts should also be made to
      increase participation of elderly patients with NSCLC in clinical trials, thereby
      enhancing evidence-based treatment decisions for this majority group. This will
      require overcoming barriers relating to trial design and to physician and patient
      awareness and attitudes. 

PMID- 25060422
TI  - Rosacea and chronic rhinosinusitis: a case-controlled study.
AB  - OBJECTIVE: To determine the relationship between rosacea, chronic rhinosinusitis
      (CRS), and the clinical presentation of rosacea. SUBJECTS AND METHOD: Twenty
      eight female Saudi patients diagnosed with rosacea at the Dermatology Clinic,
      King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia,
      between September 2011 and September 2012 and 20 age- and sex-matched control
      patients were included in the study. Paranasal sinus X-rays and assessments of
      the serum concentration of IgE (ImmunoCAP test; Phadia Laboratory Systems) were
      performed in both groups. RESULT: The rosacea patients had significantly more
      radiological evidence of CRS than the patients without rosacea [19 (67.9%) vs. 4
      (20%), p = 0.003]. The median IgE concentration was similar in both groups (225.4
      vs. 223.1 kU/l). Nine rosacea patients (32.1%) without radiological evidence of
      CRS did not have a significantly different median concentration of IgE compared
      with those who had radiological evidence of CRS (190.5 vs. 111.5 kU/l, p =
      0.859). Erythematotelangiectatic severity was significantly associated with CRS
      (p = 0.038). Serum IgE did not correlate with the severity of the facial
      condition. CONCLUSION: Patients with rosacea and CRS manifested severe
      erythematotelangiectatic rosacea. There was enough evidence to suggest an
      association between rosacea and CRS. Clinical and radiological assessments of the
      paranasal sinuses are recommended.

PMID- 25060423
TI  - The effect of facilitated tucking on procedural pain control among premature
      babies.
AB  - AIMS AND OBJECTIVES: To determine the effectiveness of facilitated tucking in
      reducing pain when venepuncture is being performed on preterm infants.
      BACKGROUND: Preterm neonates are exposed to a myriad of invasive, often painful,
      procedures throughout their stay in the neonatal intensive care unit. A growing
      volume of evidence shows that pain in preterm infants has both short- and long
      term deleterious effects. It is within the power and ethical responsibility of
      neonatal nurses to help premature babies cope with procedural pain. DESIGN: A
      quasi-experimental study with two groups: control and treatment group. METHODS: A
      study was conducted on a cohort of preterm infants (n = 42), divided into control
      (n = 21) and treatment (n = 21) groups, to determine the effect of facilitated
      tucking on pain relief during venepuncture on preterm infants in the neonatal
      intensive care unit. The severity of pain was measured using the Premature Infant
      Pain Profile score. The primary outcome measure was reduction in the Premature
      Infant Pain Profile scores. RESULTS: The Premature Infant Pain Profile score for
      the treatment group was significantly lower (M = 6.62, SD 2.598) than for the
      control group (6.62 +/- 2.60 vs. 8.52 +/- 2.99, respectively, t = -2.202, p <
      0.05). CONCLUSIONS: Facilitated tucking reduced the Premature Infant Pain Profile
      scores in preterm infants. RELEVANCE TO CLINICAL PRACTICE: The findings of this
      study suggest that facilitated tucking is able to alleviate pain; therefore,
      nurses must be able to carry out facilitated tucking when necessary.

PMID- 25060425
TI  - Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has
      prognostic significance in hepatocellular carcinoma.
AB  - BACKGROUND: Karyopherin alpha 2 (KPNA2) promotes tumor growth in hepatocellular
      carcinoma (HCC). We aimed to determine the content and clinical significance of
      mechanism underlying. METHODS: The association of transcriptional factor
      pleomorphic adenoma gene 1 (PLAG1) with KPNA2 was explored by co
      immunoprecipitation. In vitro gain- and loss-of-function models were established
      to explore the functional interaction. Clinical samples from 314 HCC patients
      were applied to explore the clinical significance. RESULTS: We found that PLAG1
      could associate with KPNA2 and be promoted into nucleus by KPNA2. The increment
      of proliferative and metastatic abilities by KPNA2 over-expression can be
      significantly retarded by PLAG1 inhibition. The co-enrichment of KPNA2 and PLAG1
      in nucleus is observed in clinical samples and can distinguish patients with the
      worst prognosis. The positive PLAG1 expression is an independent risk factor of
      recurrence free survival (HR: 1.766, 1.315-2.371; P = 0.000) and overall survival
      (HR: 1.589, 1.138-2.220; P = 0.007). Especially for patients with positive KPNA2
      staining (N = 152), the positive PLAG1 expression is the sole risk factor for
      both recurrence free survival (HR: 1.749, 1.146-2.670; P = 0.010) and overall
      survival (HR: 1.662, 1.007-2.744; P = 0.047). CONCLUSIONS: The nuclear import of
      PLAG1 by KPNA2 is essential for the role of KPNA2 in HCC cells and is significant
      to predict poor survival of HCC patients after hepatectomy.

PMID- 25060424
TI  - Eribulin mesylate reduces tumor microenvironment abnormality by vascular
      remodeling in preclinical human breast cancer models.
AB  - Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge
      natural product halichondrin B and an inhibitor of microtubule dynamics. Some
      tubulin-binding drugs are known to have antivascular (antiangiogenesis or
      vascular-disrupting) activities that can target abnormal tumor vessels. Using
      dynamic contrast-enhanced MRI analyses, here we show that eribulin induces
      remodeling of tumor vasculature through a novel antivascular activity in MX-1 and
      MDA-MB-231 human breast cancer xenograft models. Vascular remodeling associated
      with improved perfusion was shown by Hoechst 33342 staining and by increased
      microvessel density together with decreased mean vascular areas and fewer
      branched vessels in tumor tissues, as determined by immunohistochemical staining
      for endothelial marker CD31. Quantitative RT-PCR analysis of normal host cells in
      the stroma of xenograft tumors showed that eribulin altered the expression of
      mouse (host) genes in angiogenesis signaling pathways controlling endothelial
      cell-pericyte interactions, and in the epithelial-mesenchymal transition pathway
      in the context of the tumor microenvironment. Eribulin also decreased hypoxia
      associated protein expression of mouse (host) vascular endothelial growth factor
      by ELISA and human CA9 by immunohistochemical analysis. Prior treatment with
      eribulin enhanced the anti-tumor activity of capecitabine in the MDA-MB-231
      xenograft model. These findings suggest that eribulin-induced remodeling of
      abnormal tumor vasculature leads to a more functional microenvironment that may
      reduce the aggressiveness of tumors due to elimination of inner tumor hypoxia.
      Because abnormal tumor microenvironments enhance both drug resistance and
      metastasis, the apparent ability of eribulin to reverse these aggressive
      characteristics may contribute to its clinical benefits. 

PMID- 25060426
TI  - Threshold selection criteria for quantification of lumbosacral cerebrospinal
      fluid and root volumes from MRI.
AB  - BACKGROUND AND PURPOSE: The high variability of CSF volumes partly explains the
      inconsistency of anesthetic effects, but may also be due to image analysis
      itself. In this study, criteria for threshold selection are anatomically defined.
      METHODS: T2 MR images (n = 7 cases) were analyzed using 3-dimentional software.
      Maximal-minimal thresholds were selected in standardized blocks of 50 slices of
      the dural sac ending caudally at the L5-S1 intervertebral space (caudal blocks)
      and middle L3 (rostral blocks). Maximal CSF thresholds: threshold value was
      increased until at least one voxel in a CSF area appeared unlabeled and decreased
      until that voxel was labeled again: this final threshold was selected. Minimal
      root thresholds: thresholds values that selected cauda equina root area but not
      adjacent gray voxels in the CSF-root interface were chosen. RESULTS: Significant
      differences were found between caudal and rostral thresholds. No significant
      differences were found between expert and nonexpert observers. Average max/min
      thresholds were around 1.30 but max/min CSF volumes were around 1.15. Great
      interindividual CSF volume variability was detected (max/min volumes 1.6-2.7).
      CONCLUSIONS: The estimation of a close range of CSF volumes which probably
      contains the real CSF volume value can be standardized and calculated prior to
      certain intrathecal procedures.

PMID- 25060427
TI  - Highly increased risk of type 2 diabetes in patients with binge eating disorder
      and bulimia nervosa.
AB  - OBJECTIVE: We aimed to examine the prevalence and incidence of type 2 diabetes
      (T2D) in a large patient cohort treated for binge eating disorder (BED), bulimia
      nervosa (BN), and anorexia nervosa. METHOD: Patients (N = 2,342) treated at the
      Eating Disorder Unit of Helsinki University Central Hospital over the period up
      to 16 years were compared with matched general population controls (N = 9,368) in
      three stages: before entering to the treatment for an eating disorder, after the
      entrance until the end of the study period, and combined any time before, during,
      and after the treatment. The study population was linked with the oral TSD
      medication data of 17 years from The Medical Reimbursement Register. Data were
      analyzed using conditional and Poisson regression models. RESULTS: Before
      entering to the treatment for eating disorders, the risk of T2D was substantially
      increased in patients compared with controls (OR 6.6, 95% CI 4.0-10.7). At the
      end of the study period, the lifetime prevalence of T2D was 5.2% among patients,
      1.7% among controls (OR 3.4, 95% CI 2.6-4.4), and in male patients, it was
      significantly higher compared with females. Of those treated for BED, every third
      had T2D by the end of the study period (OR 12.9, 95% CI 7.4-22.5), whereas the
      same was true for 4.4% of those with BN (OR 2.4, 95% CI 1.7-3.5). DISCUSSION: Our
      findings provide strong support for the association between T2D and clinically
      significant binge eating. Disturbed glucose metabolism may contribute to the
      onset and maintenance of BED and BN.

PMID- 25060428
TI  - Patients are a virtue.

PMID- 25060429
TI  - Medical emergencies: auto-injector confusion.

PMID- 25060430
TI  - Oral health: bamboo salt.

PMID- 25060431
TI  - Pharmacology: a new bleeding issue.

PMID- 25060433
TI  - View from my window: venerable views.

PMID- 25060432
TI  - Unreliable data.

PMID- 25060434
TI  - Facial burns: acid drops.

PMID- 25060435
TI  - Systemic diseases: periodontitis and Alzheimer's.

PMID- 25060437
TI  - Annual retention fee: GDC plans 64% ARF increase for dentists.

PMID- 25060438
TI  - BDJ readers respond to ARF hike.

PMID- 25060443
TI  - An oral surgeon's life: Abanazar the surgeon.

PMID- 25060445
TI  - Oxen thigh bones to make wartime brushes.

PMID- 25060451
TI  - Independence and oral health: implications of the Scottish referendum.
AB  - On 18 September 2014, a referendum will be held on Scotland becoming a nation
      independent from the rest of the United Kingdom. Since devolution in 1999 child
      dental health in Scotland has improved significantly, although the National
      Health Service in Scotland has always been governed through a separate
      legislative framework from that in England and Wales. Scotland was also first to
      introduce a ban on smoking in public places and is pursuing minimum alcohol
      pricing to directly improve public health. This article explores if a vote for an
      independent Scotland would influence either dental and/or general health. 

PMID- 25060452
TI  - Oral health of adult prisoners and factors that impact on oral health.
AB  - The first article in this series identified the medical and mental health issues
      among male patients in comparison to the general population. This article will
      discuss the oral health of male prisoners and those factors that impact upon
      their oral health including barriers to care. In general, the oral health of
      prisoners is poorer than that of age matched controls. A variety of factors
      including health related behaviours and pre-confinement access to dental services
      can influence this. 

PMID- 25060453
TI  - General medicine and surgery for dental practitioners: part 4. Infections and
      infection control.
AB  - Infection control and knowledge of common infectious agents is a cornerstone of
      safe dental practice. This paper summarises the measures that need to be taken to
      control cross infection and discusses some of the infectious agents of concern to
      dental practitioners. 

PMID- 25060458
TI  - Summary of: the assessment of oral dryness by photographic appearance of the
      tongue.

PMID- 25060459
TI  - Summary of: preaching to the converted - optimising adverse drug reaction
      reporting by dentists.

PMID- 25060460
TI  - Student-led oral health education for the homeless community of East London.
AB  - Within the BDS curriculum, dental public health and the importance of social
      responsibility is clearly emphasised though often in a didactic manner, without
      practical application. Preventative concepts are taught and relayed to individual
      patients being treated within a dental school. The impact of oral disease on
      general health within disadvantaged communities is a problem commonly addressed
      by healthcare professionals. Part of this responsibility should be shared with
      and experienced by the next generation of dental practitioners through health
      education outreach programmes within the undergraduate curriculum. Not only will
      this benefit recipients within disadvantaged populations such as the homeless,
      but it will also develop and encourage a philosophy of social responsibility
      throughout the future careers of undergraduate dental and hygiene/therapy
      students. To explore the feasibility of achieving this objective, we devised an
      oral health awareness programme to address the needs of 'hard to reach' homeless
      people within the communities served by the Community Dental Service of Tower
      Hamlets, City and Hackney, London. 

PMID- 25060461
TI  - Patients are asking about e-cigarettes. What do we tell them?
AB  - E-cigarettes are electronic devices that deliver vaporised nicotine liquid into
      the lungs. Since the introduction of e-cigarettes in 2004, the market in the UK
      has rapidly expanded and increasingly people are asking health professionals
      about them. This article gives an overview of e-cigarettes, their use, their
      regulatory status and evidence for their safety, quality and efficacy. Advice
      about e-cigarettes for dental health professionals to give patients is provided,
      as well as the five questions, proposed by Action on Smoking and Health, to
      consider when deciding whether to permit or prohibit use of e-cigarettes on
      premises. 

PMID- 25060478
TI  - The assessment of oral dryness by photographic appearance of the tongue.
AB  - BACKGROUND: Oral dryness or hyposalivation is a major clinical problem. Several
      chairside tests or visual inspections of the oral cavity have been proposed for
      the assessment. OBJECTIVE: To identify whether photographs of the tongue could be
      used to identify oral dryness. MATERIAL AND METHODS: Twenty-five dentists and 25
      individuals with another academic background were recruited. They assessed the
      severity of the oral dryness of 50 patients, based on an intraoral picture of
      each patient. The oral dryness was quantified with a five-point Likert scale and
      the scores were subsequently compared with the salivary flow rate and the level
      of xerostomia of these patients. RESULTS: No relation was found between the
      unstimulated salivary flow rate of a patient and the average oral dryness score,
      determined by dentists (p = 0.260) as well as non-dentists (p = 0.806). Also no
      relation was found between the self-reported xerostomia level of the patient and
      the average dryness score assessed by the dentists (p = 0.171) or non-dentists (p
      = 0.477). CONCLUSION: It does not seem possible to diagnose oral dryness by mere
      visual inspection of photographed tongues. Thus, for correct diagnosis of oral
      dryness further clinical investigation of the oral cavity and collection of
      saliva is indicated.

PMID- 25060479
TI  - Preaching to the converted - optimising adverse drug reaction reporting by
      dentists.
AB  - OBJECTIVE: To assess the level of knowledge and reporting of adverse drug
      reactions (ADRs) of dentists at different stages of their careers and conduct a
      training need analysis. DESIGN: Structured questionnaires were distributed to
      final year dental students (DSs), foundation year one students (DF1s) and general
      dental practitioners (GDPs). SETTING: Opportunity samples of DSs from Kings
      College London, DF1s from the postgraduate deaneries of Kent, Surrey and Sussex,
      and Oxford and GDPs in Hampshire and the Isle of Wight. The study was conducted
      from November 2012 to February 2013. MAIN OUTCOME MEASURES: Relative knowledge
      and awareness of ADRs and ADR reporting, and performance in an assessment of
      these aspects. RESULTS: Thirty-one DSs, 35 DF1s and 98 GDPs took part in the
      study. Awareness of the Yellow Card Scheme varied between groups (30.8%, 48.6%
      and 88.8% respectively). Reported use of the scheme was uniformly low (2.6%, 5.7%
      and 5.1% respectively). There were no differences in knowledge about ADRs and ADR
      reporting between the three groups of dentists as indicated by median scores
      achieved in the questionnaire test (54%, 73% and 62% for DSs, DF1s and GDPs
      respectively; p = 0.638). All of the DSs, 91.4% of DF1s and 91.8% of GDPs said
      that they would welcome further training. Key topics included training on ADRs to
      medicines commonly used in their dental practice and deciding what ADRs needed to
      be reported. The most popular format for delivery of this training was formal
      lectures for DF1s and GDPs, but workshops for DSs. Postgraduate deaneries were
      the most popular provider choice for DF1s and GDPs. CONCLUSIONS: Dentists at
      different stages of their careers showed variable awareness and knowledge of the
      UK Yellow Card Scheme and what to report. Training should be tailored to fit the
      needs of the different groups. A questionnaire survey incorporating a summative
      knowledge assessment demonstrated variable levels of knowledge about adverse drug
      reactions and what to report. Large majorities of all groups (>90%) expressed a
      desire for training in these areas and in the case of graduate and practising
      dentists, indicated that this should be organised by the postgraduate deaneries.

PMID- 25060480
TI  - Blood sugar levels are higher in obese young children in Sweden than in Poland.
AB  - AIM: An elevated fasting glucose level is an early sign of metabolic dysfunction
      in obese children. This study compared fasting glucose levels in obese young
      children in Poland and Sweden. METHODS: We identified 109 obese children aged
      between two and 10 years from a Polish obesity register, with a mean BMI SDS (SD)
      of 3.72 (0.86). Each Polish child was matched by gender, age and degree of
      obesity, with ten children (n = 1090) from BORIS, the Swedish national childhood
      obesity treatment register. A group of 86 Swedish nonobese children served as
      controls. RESULTS: The mean fasting glucose values of the Polish, Swedish and
      nonobese cohorts were 4.73 (0.51) mmol/L, 4.92 (0.50) mmol/L and 4.56 (0.39)
      mmol/L, respectively. After adjusting for variables affecting fasting glucose,
      the mean glucose value of the Swedish obese children was 0.20 mmol/L higher than
      that of Polish obese children (p < 0.0001) and 0.41 mmol/L higher than in
      nonobese controls (p < 0.0001). CONCLUSION: Swedish obese young children had
      higher glucose levels than Polish obese young children. This suggests that
      Swedish obese children face a higher risk of the prediabetic stage impaired
      fasting glycaemia.

PMID- 25060481
TI  - Germ cell tumors in children and adolescents in Finland: trends over 1969-2008.
AB  - PURPOSE: Malignant germ cell tumors (GCTs) are a heterogeneous group of neoplasms
      putatively originating from the primordial germ cell. In adults, an increasing
      incidence of GCTs, particularly testicular tumors, has been reported in recent
      decades. However, population-based evidence in children and adolescents remains
      limited. We investigated the incidence of malignant GCTs diagnosed in childhood
      or adolescence, using population-based nationwide data from Finland. METHODS: We
      obtained information from the Finnish Cancer Registry on all malignant GCTs
      registered in 1969-2008 in children or adolescents aged 0-19 years. Data on tumor
      location, histology, stage, and survival were collected. Age-standardized
      incidence and survival rates were calculated. RESULTS: A total of 334 cases of
      malignant GCT were identified. Their proportion among all malignant tumors among
      0- to 19-year-olds increased from 3 to 9.7% in boys with time, but remained
      stable in girls (3%). The overall incidence rate was 0.6 per 100,000 (0.8 in boys
      and 0.4 in girls), and differed significantly between the age groups. A
      significant increase in the incidence of testicular GCTs was seen in boys in the
      age group of 15-19 years. CONCLUSIONS: Although malignant GCTs are rare, their
      relative frequency in children and adolescents has increased during recent
      decades, the change being mainly due to an increasing frequency of the testicular
      tumors among teenagers. The causes of the increase remain unknown, but
      environmental exposures are likely to be involved.

PMID- 25060483
TI  - Synthesis of multisubstituted 2-aminopyrroles/pyridines via chemoselective
      Michael addition/intramolecular cyclization reaction.
AB  - A facile and efficient synthetic strategy to construct polysubstituted 2
      aminopyrroles/pyridines was developed via chemoselective Michael
      addition/intramolecular cyclization reaction under very mild conditions. It
      suggested that the chemoselectivity of the process could be controlled by the
      leaving ability of the halides. 

PMID- 25060482
TI  - Sedentary behavior is associated with colorectal adenoma recurrence in men.
AB  - PURPOSE: The association between physical activity and colorectal adenoma is
      equivocal. This study was designed to assess the relationship between physical
      activity and colorectal adenoma recurrence. METHODS: Pooled analyses from two
      randomized, controlled trials included 1,730 participants who completed the
      Arizona Activity Frequency Questionnaire at baseline, had a colorectal adenoma
      removed within 6 months of study registration, and had a follow-up colonoscopy
      during the trial. Logistic regression modeling was employed to estimate the
      effect of sedentary behavior, light-intensity physical activity, and moderate
      vigorous physical activity on colorectal adenoma recurrence. RESULTS: No
      statistically significant trends were found for any activity type and odds of
      colorectal adenoma recurrence in the pooled population. However, males with the
      highest levels of sedentary time experienced 47% higher odds of adenoma
      recurrence. Compared to the lowest quartile of sedentary time, the ORs (95% CIs)
      for the second, third, and fourth quartiles among men were 1.23 (0.88, 1.74),
      1.41 (0.99, 2.01), and 1.47 (1.03, 2.11), respectively (p(trend) = 0.03). No
      similar association was observed for women. CONCLUSIONS: This study suggests that
      sedentary behavior is associated with a higher risk of colorectal adenoma
      recurrence among men, providing evidence of detrimental effects of a sedentary
      lifestyle early in the carcinogenesis pathway.

PMID- 25060484
TI  - PTR-TOF-MS analysis of volatile compounds in olive fruits.
AB  - BACKGROUND: Volatile compounds of Cellina di Nardo and Ogliarola Barese, two
      typical Italian olive varieties, have been characterised at different ripening
      stages. Proton transfer reaction-time-of-flight-mass spectrometry (PTR-TOF-MS)
      was used for the first time on these fruits with the aim of characterising the
      volatile profile and, in the case of Ogliarola, the changes which may occur
      during the maturation process. RESULTS: PTR-TOF-MS does not involve any sample
      pre-treatment, and allows high-resolution measurements, large spectra and small
      fragmentation of the volatiles. Therefore it allows both compound identification
      and data statistical treatments. In the present work, about 40 compounds that
      contribute to the discrimination between samples of the two varieties have been
      identified. CONCLUSIONS: Three groups of compounds were identified: (1) compounds
      that are typical of mature fruits of Ogliarola, (2) compounds that tend to
      decrease during the change from green to mature fruits, and (3) compounds that
      increase during the maturation process.

PMID- 25060485
TI  - Chrysanthemum CmNAR2 interacts with CmNRT2 in the control of nitrate uptake.
AB  - Nitrate transporters are an important component of plant growth and development.
      Chrysanthemum morifolium is an important ornamental species, for which a
      sufficient supply of nitrogenous fertilizer is required to maintain economic
      yields. In this study, the full-length cDNA of the nitrate transporter genes
      CmNRT2 and CmNAR2 were isolated. CmNRT2 transcript accumulation was inducible by
      both nitrate and ammonium, but the latter ion down-regulated the transcript
      accumulation of CmNAR2. CmNRT2 might be a plasma membrane localized protein,
      while CmNAR2 was distributed throughout the cell. CmNAR2 was shown to interact
      with CmNRT2 by in vitro and in vivo assays. Arabidopsis thaliana plants
      heterologously expressing CmNRT2 showed an increased rate of nitrate influx,
      while this trait was unaltered in plants expressing CmNAR2. Double transformants
      (CmNRT2 plus CmNAR2) exhibited an enhanced rate of nitrate influx into the root.
      Our data indicated that the interaction of CmNAR2 with CmNRT2 contributed to the
      uptake of nitrate. 

PMID- 25060486
TI  - Construction and radiolabeling of adenovirus variants that incorporate human
      metallothionein into protein IX for analysis of biodistribution.
AB  - Using adenovirus (Ad)-based vectors is a promising strategy for novel cancer
      treatments; however, current tracking approaches in vivo are limited. The C
      terminus of the Ad minor capsid protein IX (pIX) can incorporate heterologous
      reporters to monitor biodistribution. We incorporated metallothionein (MT), a low
      molecular-weight metal-binding protein, as a fusion to pIX. We previously
      demonstrated 99mTc binding in vitro to a pIX-MT fusion on the Ad capsid. We
      investigated different fusions of MT within pIX to optimize functional display.
      We identified a dimeric MT construct fused to pIX that showed significantly
      increased radiolabeling capacity. After Ad radiolabeling, we characterized metal
      binding in vitro. We explored biodistribution in vivo in control mice, mice
      pretreated with warfarin, mice preimmunized with wild-type Ad, and mice that
      received both warfarin pretreatment and Ad preimmunization. Localization of
      activity to liver and bladder was seen, with activity detected in spleen,
      intestine, and kidneys. Afterwards, the mice were euthanized and selected organs
      were dissected for further analysis. Similar to the imaging results, most of the
      radioactivity was found in the liver, spleen, kidneys, and bladder, with
      significant differences between the groups observed in the liver. These results
      demonstrate this platform application for following Ad dissemination in vivo.

PMID- 25060487
TI  - The good EULAR response at the first year is strongly predictive of clinical
      remission in rheumatoid arthritis: results from the TARAC cohort.
AB  - The purpose of this study was to identify the prevalence and prognostic factors
      of clinical remission in patients with rheumatoid arthritis (RA). The Thai Army
      Rheumatoid Arthritis Cohort (TARAC) patients were included if baseline data were
      available. Clinical remission was defined as 28-joint count disease activity
      scores (DAS28) <2.6 in the last two consecutive visits, at least 3 months apart.
      Three hundred and thirty-five patients were enrolled, and 89.9 % were female.
      Mean (SD) age was 61 years (11.4), and mean disease duration was 145.9 months
      (93.7). Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)
      were positive in 69.9 and 67.8 %, respectively. Eighty-nine percent of patients
      were treated with synthetic DMARDs, of which 29 % received monotherapy. The
      combination of biologic and synthetic DMARDs was used in 10.4 % of the patients.
      Clinical remission was observed in 49 patients (14.6 %). Early diagnosis and
      treatment within 12 months of onset (odds ratio (OR) 1.95, 95 % confidence
      interval (CI) 1.02-3.74, p = 0.04), rheumatoid factor negativity (OR 2.10, 95 %
      CI 1.04-4.21, p = 0.04) and good EULAR response at the end of the first year of
      treatment (OR 2.75, 95 % CI 1.08-6.99, p = 0.03) were associated with clinical
      remission in univariate analysis. In multivariate regression analysis, only a
      good EULAR response at the first year was significantly correlated with clinical
      remission in this study (OR 3.1, 95 % CI 1.15-8.36, p = 0.03). Although remission
      is currently a treatment goal in patients with RA, only one-seventh of patients
      have achieved sustained clinical remission in clinical practice. The good EULAR
      response at the end of the first year was an independent predictive factor of
      clinical remission. 

PMID- 25060489
TI  - Genetic variants in AKT1 gene were associated with risk and survival of OSCC in
      Chinese Han Population.
AB  - BACKGROUND: AKT1 is an important downstream effector of PTEN/PI3K/AKT signal
      transduction pathway. Aberrant expression and genetic variant of AKT1 gene are
      suggested to be involved in several types of human cancers, including OSCC. The
      aim of this study was to investigate the possible association between AKT1 gene
      polymorphisms and OSCC in Chinese Han Population. METHODS: A total of 182 OSCC
      patients and 207 cancer-free controls were enrolled for this hospital-based
      study. Five single-nucleotide polymorphisms (SNPs) on AKT1 (rs1130214, rs1130233,
      rs2494732, rs3730358, rs3803300) were investigated and genotyped by Sequenom Mass
      ARRAY & iPLEX-MALDI-TOF technology. Chi-square test, SHEsis software, and Kaplan
      Meier method were used to evaluate the relationship between selected SNPs and
      OSCC susceptibility and progression. RESULTS: Significant difference of genotype
      distribution was observed between cases and control group at SNP sites rs1130214
      (P = 0.006) and rs3803300 (P = 0.033, P = 0.003 for heterozygote and homozygous
      mutant, respectively). In the haplotype analysis, haplotype H4 which contained
      mutant-type allele of rs1130214 and rs3803300 was also related to OSCC risk (OR =
      1.974, 95% CI = 1.048-3.718). Moreover, CT genotype of rs3730358 was associated
      with higher risk of OSCC progression (HR = 2.466, 95% CI = 1.017-5.981).
      CONCLUSION: Our results indicated that rs1130214 and rs3803300 were related to
      OSCC susceptibility in Chinese Han Population. In addition, rs3730358 might be
      associated with progression-free survival time of OSCC patients, suggesting that
      this SNP could be a potential prognosis marker for OSCC.

PMID- 25060488
TI  - Contemporary gene flow between wild An. gambiae s.s. and An. arabiensis.
AB  - BACKGROUND: In areas where the morphologically indistinguishable malaria
      mosquitoes Anopheles gambiae Giles and An. arabiensis Patton are sympatric,
      hybrids are detected occasionally via species-diagnostic molecular assays. An.
      gambiae and An. arabiensis exhibit both pre- and post-reproductive mating
      barriers, with swarms largely species-specific and male F1 (first-generation)
      hybrids sterile. Consequently advanced-stage hybrids (back-crosses to parental
      species), which would represent a route for potentially-adaptive introgression,
      are expected to be very rare in natural populations. Yet the use of one or two
      physically linked single-locus diagnostic assays renders them indistinguishable
      from F1 hybrids and levels of interspecific gene flow are unknown. METHODS: We
      used data from over 350 polymorphic autosomal SNPs to investigate post F1 gene
      flow via patterns of genomic admixture between An. gambiae and An. arabiensis
      from eastern Uganda. Simulations were used to investigate the statistical power
      to detect hybrids with different levels of crossing and to identify the hybrid
      category significantly admixed genotypes could represent. RESULTS: A range of
      admixture proportions were detected for 11 field-collected hybrids identified via
      single-locus species-diagnostic PCRs. Comparison of admixture data with
      simulations indicated that at least seven of these hybrids were advanced
      generation crosses, with backcrosses to each species identified. In addition, of
      36 individuals typing as An. gambiae or An. arabiensis that exhibited outlying
      admixture proportions, ten were identified as significantly mixed backcrosses,
      and at least four of these were second or third generation crosses. CONCLUSIONS:
      Our results show that hybrids detected using standard diagnostics will often be
      hybrid generations beyond F1, and that in our study area around 5% (95%
      confidence intervals 3%-9%) of apparently 'pure' species samples may also be
      backcrosses. This is likely an underestimate because of rapidly-declining
      detection power beyond the first two backcross generations. Post-F1 gene flow
      occurs at a far from inconsequential rate between An. gambiae and An. arabiensis,
      and, especially for traits under strong selection, could readily lead to adaptive
      introgression of genetic variants relevant for vector control.

PMID- 25060490
TI  - Durable benefit and the potential for long-term survival with immunotherapy in
      advanced melanoma.
AB  - Historically, the median overall survival for patients with stage IV melanoma was
      less than 1 year and the 5-year survival rate was ~10%. Recent advances in
      therapy have raised 5-year survival expectations to ~20%. Notably, a subset of
      melanoma patients who receive immunotherapy with high-dose interleukin-2, and now
      ipilimumab, can achieve long-term survival of at least 5 years. A major goal in
      melanoma research is to increase the number of patients who experience this
      overall survival benefit. In this review, we discuss the attributes of
      immunotherapy and newer targeted agents, and consider how combination strategies
      might improve the chances of achieving durable benefit and long-term survival. We
      also discuss three areas that we believe will be critical to making further
      advances in melanoma treatment. To better understand the clinical profile of
      patients who achieve long-term survival with immunotherapy, we first present data
      from ipilimumab clinical trials in which a subset of patients experienced durable
      responses. Second, we discuss the limitations of traditional metrics used to
      evaluate the benefits of immunotherapies. Third, we consider emerging issues that
      clinicians are currently facing when making treatment decisions regarding
      immunotherapy. A better understanding of these novel treatments may improve
      survival outcomes in melanoma, increase the number of patients who experience
      this overall survival benefit, and inform the future use of these agents in the
      treatment of other cancer types.

PMID- 25060491
TI  - Compulsive-like responding for opioid analgesics in rats with extended access.
AB  - The abuse of prescription opioids that are used for the treatment of chronic pain
      is a major public health concern, costing ~$53.4 billion annually in lost wages,
      health-care costs, and criminal costs. Although opioids remain a first-line
      therapy for the treatment of severe chronic pain, practitioners remain cautious
      because of the potential for abuse and addiction. Opioids such as heroin are
      considered very rewarding and reinforcing, but direct and systematic comparisons
      of compulsive intake between commonly prescribed opioids and heroin in animal
      models have not yet been performed. In the present study, we evaluated the
      potential for compulsive-like drug seeking and taking, using intravenous self
      administration of oxycodone, fentanyl, and buprenorphine in rats allowed long
      access sessions (12 h). We measured compulsive-like intake using an established
      escalation model and responding on a progressive ratio schedule of reinforcement.
      We compared the potential for compulsive-like self-administration of these
      prescription opioids and heroin, which has been previously established to induce
      increasing intake that models the transition to addiction in humans. We found
      that animals that self-administered oxycodone, fentanyl, or heroin, but not
      buprenorphine had similar profiles of escalation and increases in breakpoints.
      The use of extended access models of prescription opioid intake will help better
      understand the biological factors that underlie opioid dependence. 

PMID- 25060492
TI  - Addition of taxane to induction therapy in head and neck malignancies: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Head and neck cancer, mostly squamous cell carcinoma, ranks sixth
      among the most common cancers. Despite progress in treatment in recent years,
      survival remains poor. Since induction chemotherapy has been associated with
      survival benefit, it is a reasonable treatment option. The standard protocol up
      to recently has been cisplatin and 5-flourouracil. The addition of taxanes to the
      standard induction protocol has shown superiority in terms of the overall
      response rate. Nevertheless, not all trials demonstrated survival benefit. We
      aimed to evaluate the effect of taxane added to the standard protocol of
      induction therapy. METHODS: We performed a systematic review and meta-analysis of
      randomized controlled trials that compared the addition of taxane to the standard
      induction protocol of cisplatin and 5-flourouracil for patients with head and
      neck malignancy. We searched The Cochrane library, PubMed, LILACS, conference
      proceedings, and references of published trials. Two reviewers independently
      assessed the quality of the trials and extracted data. Hazard ratios (HRs) for
      time-to-event were determined and pooled. RESULTS: A total of 4 trials comprising
      1,441 patients were included in this meta-analysis. All patients were available
      for the meta-analysis of overall survival. Patients treated with the addition of
      taxane had statistically significant overall survival [HR = 0.82, 95% confidence
      interval (CI) 0.71-0.94] and progression-free survival (HR = 0.82, 95% CI 0.72
      0.93). No effect was observed in larynx preservation rate (relative risk = 0.88,
      95% CI 0.64-1.19). The rate of hematological adverse events was higher in the
      taxane group than in the control group. CONCLUSIONS: These results suggest that
      induction therapy with the addition of taxane is superior to induction therapy
      with cisplatin and 5-flourouracil in terms of overall survival and progression
      free survival. The higher rate of neutropenia and neutropenic fever should be
      taken into consideration when making treatment decisions.

PMID- 25060493
TI  - Microcell parasites of molluscs: introduction to DAO Special 7.
AB  - First discovered decades ago, microcell protistan parasites of the genera Bonamia
      and Mikrocytos remain relevant today for their economic impacts on growing
      molluscan aquaculture industries and fisheries. Bonamia parasites have received
      more attention over the years in part because they are more widespread and thus
      of wider concern, but there has been renewed interest in Mikrocytos recently with
      the generation of important new findings. Among these has been the surprising
      observation that Mikrocytos has phylogenetic affinities to the Rhizaria, which
      includes the haplosporidian protists and the genus Bonamia. This Diseases of
      Aquatic Organisms Special, emerging from the 5th Meeting of the Microcell Working
      Group held at the Central Veterinary Institute, Lelystad, the Netherlands, in
      February 2012, presents new insights into Mikrocytos and Bonamia diversity,
      distributions, diagnostics, ultrastructure, and infection dynamics, and captures
      major developments in the field since the last review of these genera in 2004. 

PMID- 25060494
TI  - Bonamia parasites: a rapidly changing perspective on a genus of important mollusc
      pathogens.
AB  - Organisms of the genus Bonamia are intracellular protistan parasites of oysters.
      To date, 4 species have been described (B. ostreae, B. exitiosa, B. perspora and
      B. roughleyi), although the status of B. roughleyi is controversial. Introduction
      especially of B. ostreae and B. exitiosa to naive host populations has been shown
      to cause mass mortalities in the past and has had a dramatic impact on oyster
      production. Both B. ostreae and B. exitiosa are pathogens notifiable to the World
      Organisation for Animal Health (OIE) and the European Union. Effective management
      of the disease caused by these pathogens is complicated by the extensive nature
      of the oyster production process and limited options for disease control of the
      cultured stocks in open water. This review focuses on the recent advances in
      research on genetic relationships between Bonamia isolates, geographical
      distribution, susceptible host species, diagnostics, epizootiology, host-parasite
      interactions, and disease resistance and control of this globally important genus
      of oyster pathogens. 

PMID- 25060495
TI  - Review of Mikrocytos microcell parasites at the dawn of a new age of scientific
      discovery.
AB  - The genus Mikrocytos is traditionally known for Mikrocytos mackini, the microcell
      parasite that typically infects Pacific oysters along the west coast of North
      America. Multiple factors have conspired to create difficulty for scientific
      research on Mikrocytos parasites. These include their tiny cell size, infections
      that are often of light intensity, lack of suitable cell lines and techniques for
      in vitro culture, and the seasonal nature of infections. The extreme rate of
      molecular evolution in Mikrocytos stymied new species discovery and confounded
      attempts to resolve its phylogenetic position for many years. Fortunately, 2
      recent landmark studies have paved the way forward for future research by
      drastically changing our understanding of the evolution and diversity of these
      parasites. No longer an orphan eukaryotic lineage, the phylogenetic placement of
      Mikrocytos has been confidently resolved within Rhizaria and as sister taxon to
      Haplosporidia. The genus has also found a taxonomic home within the newly
      discovered order, Mikrocytida - a globally distributed lineage of parasites
      infecting a wide range of invertebrate hosts. Here we review available scientific
      information on Mikrocytos parasites including their evolution and diversity, host
      and geographic ranges, epizootiology, and detection of the regulated pathogen, M.
      mackini. We also make recommendations towards a consistent taxonomic framework
      for this genus by minimally suggesting the use of 18S rDNA sequence, host species
      information, and histopathological presentation in new species descriptions. This
      is timely given that we are likely embarking on a new era of scientific
      advancements, including species discovery, in this genus and its relatives. 

PMID- 25060496
TI  - Phylogenetics of Bonamia parasites based on small subunit and internal
      transcribed spacer region ribosomal DNA sequence data.
AB  - The genus Bonamia (Haplosporidia) includes economically significant oyster
      parasites. Described species were thought to have fairly circumscribed host and
      geographic ranges: B. ostreae infecting Ostrea edulis in Europe and North
      America, B. exitiosa infecting O. chilensis in New Zealand, and B. roughleyi
      infecting Saccostrea glomerata in Australia. The discovery of B. exitiosa-like
      parasites in new locations and the observation of a novel species, B. perspora,
      in non-commercial O. stentina altered this perception and prompted our wider
      evaluation of the global diversity of Bonamia parasites. Samples of 13 oyster
      species from 21 locations were screened for Bonamia spp. by PCR, and small
      subunit and internal transcribed spacer regions of Bonamia sp. ribosomal DNA were
      sequenced from PCR-positive individuals. Infections were confirmed
      histologically. Phylogenetic analyses using parsimony and Bayesian methods
      revealed one species, B. exitiosa, to be widely distributed, infecting 7 oyster
      species from Australia, New Zealand, Argentina, eastern and western USA, and
      Tunisia. More limited host and geographic distributions of B. ostreae and B.
      perspora were confirmed, but nothing genetically identifiable as B. roughleyi was
      found in Australia or elsewhere. Newly discovered diversity included a Bonamia
      sp. in Dendostrea sandvicensis from Hawaii, USA, that is basal to the other
      Bonamia species and a Bonamia sp. in O. edulis from Tomales Bay, California, USA,
      that is closely related to both B. exitiosa and the previously observed Bonamia
      sp. from O. chilensis in Chile. 

PMID- 25060497
TI  - Ultrastructural comparison of Bonamia spp. (Haplosporidia) infecting ostreid
      oysters.
AB  - The ultrastructure of Bonamia from Ostrea angasi from Australia, Crassostrea
      ariakensis from the USA, O. puelchana from Argentina and O. edulis from Spain was
      compared with described Bonamia spp. All appear conspecific with B. exitiosa. The
      Bonamia sp. from Chile had similarities to the type B. exitiosa from New Zealand
      (NZ), but less so than the other forms recognized as B. exitiosa. Two groups of
      ultrastructural features were identified; those associated with metabolism
      (mitochondrial profiles, lipid droplets and endoplasmic reticulum), and those
      associated with haplosporogenesis (Golgi, indentations in the nuclear surface,
      the putative trans-Golgi network, perinuclear granular material and
      haplosporosome-like bodies). Metabolic features were regarded as having little
      taxonomic value, and as the process of haplosporogenesis is not understood, only
      haplosporosome shape and size may be of taxonomic value. However, the uni
      nucleate stages of spore-forming haplosporidians are poorly known and may be
      confused with Bonamia spp. uni-nucleate stages. The many forms of NZ B. exitiosa
      have not been observed in other hosts, which may indicate that it has a plastic
      life cycle. Although there are similarities between NZ B. exitiosa and Chilean
      Bonamia in the development of a larger uni-nucleate stage and the occurrence of
      cylindrical confronting cisternae, the clarification of the identity of Chilean
      Bonamia must await molecular studies. 

PMID- 25060498
TI  - Molecular taxonomy of Mikrocytos boweri sp. nov. from Olympia oysters Ostrea
      lurida in British Columbia, Canada.
AB  - Mikrocytos mackini is a microcell parasite that usually infects Crassostrea gigas
      distributed along the Pacific Northwest coast of North America. For many years,
      M. mackini was the only known species in the genus, but there have been multiple
      recent findings of genetically divergent forms of Mikrocytos in different hosts
      and in distantly located geographic locations. This note describes M. boweri sp.
      nov. found in Olympia oysters Ostrea lurida collected from and native to British
      Columbia, Canada, primarily using a molecular taxonomic approach. 

PMID- 25060499
TI  - Infection of Manila clams Ruditapes philippinarum from Galicia (NW Spain) with a
      Mikrocytos-like parasite.
AB  - The name 'microcells' is frequently used to refer to small-sized unicellular
      stages of molluscan parasites of the genera Bonamia (Rhizaria, Haplosporidia) and
      Mikrocytos (Rhizaria). Histological examination of Manila clams Ruditapes
      philippinarum revealed microcells in the connective tissue of adductor muscle,
      foot, mantle, gills, siphon and visceral mass. The clams had been collected from
      4 beds on the coast of Galicia, Spain. The prevalence of these microcells ranged
      from 73 to 93% in surface clams and from 3 to 33% in buried clams. However, the
      detection of brown ring disease signs in clams from every bed prevented us from
      making the assumption that the microcells alone were responsible for clam
      mortality. PCR assays using primer pairs designed to detect Bonamia spp. and
      haplosporidians gave negative results, whereas positive results were obtained
      with primers for the genus Mikrocytos. A consensus sequence of 1670 bp of the
      ribosomal gene complex of the microcells was obtained. It contained a section of
      the 18S region, the whole first internal transcribed spacer, the 5.8S region, the
      second internal transcribed spacer and a section of the 28S region. Comparison of
      this sequence with those of M. mackini infecting Crassostrea gigas and Mikrocytos
      sp. infecting Ostrea edulis showed that the microcells of Galician clams were the
      most divergent among the compared parasites. This is the first report of a
      Mikrocytos-like parasite infecting Manila clams. Care must be taken to avoid the
      spread of this parasite through Manila clam transfers. 

PMID- 25060500
TI  - Species-specific oligonucleotide probe for detection of Bonamia exitiosa
      (Haplosporidia) using in situ hybridisation assay.
AB  - Bonamiosis is a disease affecting various oyster species and causing oyster mass
      mortalities worldwide. The protozoans Bonamia exitiosa and B. ostreae
      (Haplosporidia) are included in the list of notifiable diseases of the World
      Organisation for Animal Health as the causative agents of this disease. Although
      the geographic range of both species was considered different for years, both
      species are now known to co-occur in some European areas affecting the same host,
      Ostrea edulis, which strengthens the need of species-specific methods to
      unequivocally identify the species of Bonamia. An oligonucleotide probe for
      specific detection of B. exitiosa (BEX_ITS) was designed to be used in in situ
      hybridisation (ISH) assays. ISH assay with BEX_ITS probe showed species
      specificity and more sensitivity than traditional histology to visualise the
      parasite inside host tissue. ISH assay showed that the oyster gonad was the area
      where the parasite was most frequently located, and was the exclusive organ of
      infection in some oysters. A recommendation arising from the study is that more
      than 1 organ (including gonad and gills) should be used for PCR-based diagnosis
      of B. exitiosa, to maximise the sensitivity. 

PMID- 25060501
TI  - Interlaboratory variability in screening for Bonamia ostreae, a protistan
      parasite of the European flat oyster Ostrea edulis.
AB  - The spread of the protozoan parasite Bonamia ostreae is of major concern to the
      European flat oyster Ostrea edulis industry. Many studies have looked at the
      sensitivity of individual methods available to screen for B. ostreae, but in this
      study, 3 separate laboratories examined 4 methods of diagnosis currently used
      routinely in laboratories: heart imprints, histology, polymerase chain reaction
      (PCR) and in situ hybridisation (ISH). The results were compared to estimate
      interlaboratory variability. Heart imprints and histology had the highest
      reproducibility amongst the 3 laboratories, with greatest agreement between
      detection of infected and uninfected individuals. PCR had the highest detection
      level in every laboratory. These positives were related to the presence of
      confirmed infections but also in unconfirmed infections, possibly due to the
      presence of traces of B. ostreae DNA in oysters where clinical infections were
      not observed. PCR, in combination with histology or ISH, provided the most
      reliable detection levels in every laboratory. Variation in results for PCR and
      ISH observed between laboratories may be due to the different protocols used by
      each laboratory for both methods. Overall, the findings from the 3 laboratories
      indicated that at least 2 methods, with fixed protocols, should be used for the
      accurate detection and determination of infection prevalence within a sample.
      This combination of methods would allow for a clearer and more precise diagnosis
      of B. ostreae, preventing further spread of the disease and providing more
      accurate detection levels and epidemiological information. 

PMID- 25060502
TI  - Epidemiology of Bonamia in the UK, 1982 to 2012.
AB  - Bonamiasis, caused by Bonamia ostreae, was confirmed in native flat oysters
      Ostrea edulis L. in England in 1982. Hudson & Hill (1991; Aquaculture 93:279-285)
      documented investigations into the initial spread of the disease in wild and
      cultivated stocks of native oysters in the UK. They also described the controls
      that were initially applied to prevent the further spread of the pathogen. This
      paper reports on subsequent controls and associated monitoring applied in the UK
      and reports on the epidemiology of the disease in the 30 yr from 1982 to 2012.
      Bonamiasis remained confined to the zones in England as documented by Hudson &
      Hill (1991) until 2005, when it was confirmed in Lough Foyle, Northern Ireland.
      In 2006 it was found in 2 new areas, one in Wales and one in Scotland. Subsequent
      further spread to additional areas in all parts of the UK has resulted in 9 zones
      being currently designated as infected with the disease. In addition, a single
      oyster from one area has tested positive for the closely related B. exitiosa. In
      general, analysis of the results of the monitoring programme in England and Wales
      shows no clear trend in infection levels over time, although there has been an
      apparent decrease in the level of infection in some fishery areas. In an autumn
      sampling programme the highest levels of infection were detected in October. 

PMID- 25060503
TI  - Thirty-year history of Irish (Rossmore) Ostrea edulis selectively bred for
      disease resistance to Bonamia ostreae.
AB  - The protistan pathogen Bonamia ostreae was first detected in Ostrea edulis at
      Rossmore, Cork Harbour, on the south coast of Ireland in 1987. A selective
      breeding programme commenced in 1988 by Atlantic Shellfish Ltd. to produce B.
      ostreae-resistant oysters using 3 to 4 yr old survivors as broodstock for
      controlled spawning in land-based spatting ponds. On-growing of oyster spat
      settled on mussel cultch was carried out on designated beds within Cork Harbour.
      Oyster production subsequently increased successfully, resulting in 3 yr old
      Rossmore O. edulis being marketed from 1993 onwards and a record tonnage of 4 yr
      old oysters being produced in 1995 and 1996. O. edulis production, B. ostreae
      prevalence and oyster mortalities have been monitored and recorded at Rossmore
      for over 30 yr. The collation and analysis of this data from 52 samples and 3190
      oysters demonstrate the introduction and progression of bonamiosis and subsequent
      interventions to ameliorate disease effects during this period at Rossmore.
      Results suggest that O. edulis mortalities are now negligible during the first 4
      yr of growth, prevalence of B. ostreae infection is low, and no correlation
      exists between prevalence of infection and oyster mortalities. This study, when
      compared to other studies of bonamiosis-infected oyster populations, suggests
      that an intervention in the form of a selective breeding programme is required to
      reduce the impact of the disease. 

PMID- 25060504
TI  - Oyster parasites Bonamia ostreae and B. exitiosa co-occur in Galicia (NW Spain):
      spatial distribution and infection dynamics.
AB  - Bonamiosis constrains the flat oyster industry worldwide. The protistan species
      Bonamia ostreae had been considered solely responsible for this disease in
      Europe, but the report of B. exitiosa infecting Ostrea edulis 5 yr ago in Galicia
      (NW Spain), and subsequently in other European countries, raised the question of
      the relevance of each species in bonamiosis. The spatial distribution of B.
      exitiosa and B. ostreae in Galicia was addressed by sampling 7 natural O. edulis
      beds and 3 culture raft areas, up to 3 times in the period 2009 to 2010. B.
      ostreae infected flat oysters in every natural bed and every raft culture area.
      True B. exitiosa infections (histological diagnosis) were detected in every raft
      culture area but only in 2 natural beds, i.e. in 4 rias. PCR-positive results for
      B. exitiosa were recorded in 4 out of 5 beds where true infections were not
      found, thus the occurrence of B. exitiosa in those 4 beds cannot be ruled out.
      Additionally, 4 cohorts of hatchery-produced oyster spat were transferred to a
      raft to analyse Bonamia spp. infection dynamics through oyster on-growing. The
      highest percentages of oysters PCR-positive for both Bonamia spp. were recorded
      in the first months of on-growing; other peaks of PCR-positive diagnosis were
      successively lower. Differences in the percentage of PCR-positive cases and in
      the prevalence of true infection between B. exitiosa and B. ostreae through on
      growing were not significant. Our results support that B. exitiosa is adapted to
      infect O. edulis in the Galician marine ecosystem. 

PMID- 25060505
TI  - Bonamiosis status in natural Ostrea puelchana beds in San Matias Gulf (Patagonia,
      Argentina), 14 years after an epizootic.
AB  - Between 1995 and 1996, Bonamia exitiosa caused an epizootic in San Matias Gulf,
      Argentina, that spread from a commercial culture site of Ostrea puelchana to
      natural beds located at the northeastern coast of the gulf. A mortality rate of
      95% was registered in cultured oysters, and oysters from natural beds were also
      affected. The aims of this study were to assess the parasite prevalence in oyster
      beds and the demographic structure 14 yr after the epizootic. Two different
      oyster beds were studied during 2009 and 2010. Parasite prevalence was studied
      related to oyster aggregation, density, sex, and oyster size. Prevalence reached
      35.3% at Las Grutas and 18.9% at Banco Reparo and was proportionally associated
      with density. Prevalence was also associated with the type of aggregation in
      Banco Reparo, where carrier oysters were more infected. Infection was independent
      of sex category, and infected oysters were larger than the non-infected ones.
      Oyster density decreased markedly compared to previous studies in both beds and
      mean sizes were lower, while prevalence doubled. Because of the persistence of
      the beds in this period, disease seems to control the population structure. 

PMID- 25060506
TI  - Bonamia exitiosa transmission among, and incidence in, Asian oyster Crassostrea
      ariakensis under warm euhaline conditions.
AB  - Previously reported in Australia, New Zealand, and more recently in Europe, the
      protistan parasite Bonamia exitiosa was also reported in the mid-Atlantic region
      of the USA after causing serious mortalities there in the Asian oyster
      Crassostrea ariakensis. At the time, this oyster was being considered for
      introduction, and the potential consequences of introducing this species were
      being assessed using field and laboratory studies. B. exitiosa emerged as the
      most serious disease threat for this oyster species, especially under warm
      euhaline conditions and for oysters <50 mm in size. To better evaluate how
      quickly this parasite may be able to spread among C. ariakensis, we investigated
      B. exitiosa transmission and incidence in C. ariakensis. During a first trial,
      potential direct transmission of B. exitiosa was evaluated by cohabitating
      infected C. ariakensis with uninfected C. ariakensis under in vivo quarantine
      conditions. In a second experiment, B. exitiosa incidence was estimated in situ
      by determining its prevalence in C. ariakensis deployed in an enzootic area after
      4, 7, 14, 21 and 28 d of exposure. Results suggest that under warm euhaline
      conditions B. exitiosa can be transmitted among C. ariakensis without requiring
      any other parasite source and that parasite incidence may be at least as high as
      40% after only 4 d exposure to an enzootic area. These results underscored the
      severity of the bonamiasis disease threat to C. ariakensis and provided further
      evidence that efforts to build an aquaculture industry based on C. ariakensis in
      the eastern USA might have been thwarted by parasitic disease. 

PMID- 25060507
TI  - Longitudinal study of winter mortality disease in Sydney rock oysters Saccostrea
      glomerata.
AB  - Winter mortality (WM) is a poorly studied disease affecting Sydney rock oysters
      Saccostrea glomerata in estuaries in New South Wales, Australia, where it can
      cause significant losses. WM is more severe in oysters cultured deeper in the
      water column and appears linked to higher salinities. Current dogma is that WM is
      caused by the microcell parasite Bonamia roughleyi, but evidence linking clinical
      signs and histopathology to molecular data identifying bonamiasis is lacking. We
      conducted a longitudinal study between February and November 2010 in 2 estuaries
      where WM has occurred (Georges and Shoalhaven Rivers). Results from molecular
      testing of experimental oysters for Bonamia spp. were compared to clinical
      disease signs and histopathology. Available environmental data from the study
      sites were also collated and compared. Oyster condition declined over the study
      period, coinciding with decreasing water temperatures, and was inversely
      correlated with the presence of histological lesions. While mortalities occurred
      in both estuaries, only oysters from the Georges River study site showed gross
      clinical signs and histological changes characteristic of WM (lesions were
      prevalent and intralesional microcell-like structures were sometimes noted). PCR
      testing for Bonamia spp. revealed the presence of an organism belonging to the B.
      exitiosa-B. roughleyi clade in some samples; however, the very low prevalence of
      this organism relative to histological changes and the lack of reactivity of
      affected oysters in subsequent in situ hybridisation experiments led us to
      conclude that this Bonamia sp. is not responsible for WM. Another aetiological
      agent and a confluence of environmental factors are a more likely explanation for
      the disease. 

PMID- 25060508
TI  - Modeling of plant in vitro cultures: overview and estimation of biotechnological
      processes.
AB  - Plant cell and tissue cultivations are of growing interest for the production of
      structurally complex and expensive plant-derived products, especially in
      pharmaceutical production. Problems with up-scaling, low yields, and high-priced
      process conditions result in an increased demand for models to provide
      comprehension, simulation, and optimization of production processes. In the last
      25 years, many models have evolved in plant biotechnology; the majority of them
      are specialized models for a few selected products or nutritional conditions. In
      this article we review, delineate, and discuss the concepts and characteristics
      of the most commonly used models. Therefore, the authors focus on models for
      plant suspension and submerged hairy root cultures. The article includes a short
      overview of modeling and mathematics and integrated parameters, as well as the
      application scope for each model. The review is meant to help researchers better
      understand and utilize the numerous models published for plant cultures, and to
      select the most suitable model for their purposes.

PMID- 25060509
TI  - A novel channel selection method for multiple motion classification using high
      density electromyography.
AB  - BACKGROUND: Selecting an appropriate number of surface electromyography (EMG)
      channels with desired classification performance and determining the optimal
      placement of EMG electrodes would be necessary and important in practical
      myoelectric control. In previous studies, several methods such as sequential
      forward selection (SFS) and Fisher-Markov selector (FMS) have been used to select
      the appropriate number of EMG channels for a control system. These exiting
      methods are dependent on either EMG features and/or classification algorithms,
      which means that when using different channel features or classification
      algorithm, the selected channels would be changed. In this study, a new method
      named multi-class common spatial pattern (MCCSP) was proposed for EMG selection
      in EMG pattern-recognition-based movement classification. Since MCCSP is
      independent on specific EMG features and classification algorithms, it would be
      more convenient for channel selection in developing an EMG control system than
      the exiting methods. METHODS: The performance of the proposed MCCSP method in
      selecting some optimal EMG channels (designated as a subset) was assessed with
      high-density EMG recordings from twelve mildly-impaired traumatic brain injury
      (TBI) patients. With the MCCSP method, a subset of EMG channels was selected and
      then used for motion classification with pattern recognition technique. In order
      to justify the performance of the MCCSP method against different electrode
      configurations, features and classification algorithms, two electrode
      configurations (unipolar and bipolar) as well as two EMG feature sets and two
      types of pattern recognition classifiers were considered in the study,
      respectively. And the performance of the proposed MCCSP method was compared with
      that of two exiting channel selection methods (SFS and FMS) in EMG control
      system. RESULTS: The results showed that in comparison with the previously used
      SFS and FMS methods, the newly proposed MCCSP method had better motion
      classification performance. Moreover, a fixed combination of the selected EMG
      channels was obtained when using MCCSP. CONCLUSIONS: The proposed MCCSP method
      would be a practicable means in channel selection and would facilitate the design
      of practical myoelectric control systems in the active rehabilitation of mildly
      impaired TBI patients and in other rehabilitation applications such as the
      multifunctional myoelectric prostheses for limb amputees.

PMID- 25060510
TI  - Disruptions in autobiographical memory processing in depression and the emergence
      of memory therapeutics.
AB  - Depression is characterized by distinct profiles of disturbance in ways
      autobiographical memories are represented, recalled, and maintained. We review
      four core domains of difficulty: systematic biases in favor of negative material;
      impoverished access and responses to positive memories; reduced access to the
      specific details of the personal past; and dysfunctional processes of rumination
      and avoidance around personal autobiographical material. These difficulties drive
      the onset and maintenance of depression; consequently, interventions targeted at
      these maladaptive processes have clinical potential. Memory therapeutics is the
      development of novel clinical techniques, translated from basic research, that
      target memory difficulties in those with emotional disorders. We discuss
      prototypical examples from this clinical domain including MEmory Specificity
      Training, positive memory elaboration, memory rescripting, and the method-of-loci
      (MoL). 

PMID- 25060511
TI  - Application and effects of neuromuscular electrical stimulation in critically ill
      patients: systematic review.
AB  - OBJECTIVE: To investigate the applications and effects of neuromuscular
      electrical stimulation (NMES) in critically ill patients in ICU by means of a
      systematic review. MATERIALS AND METHODS: Electronic searches were conducted in
      the databases Medline, CINAHL, Cochrane Central Register of Controlled Trials,
      Web of Science, Embase, ProQuest Health and Medical Complete, AMED, and PEDro.
      The PEDro score was used to assess the methodological quality of the eligible
      studies. RESULTS: The search yielded a total of 9759 titles and nine articles
      satisfied the eligibility criteria. These studies showed that NMES can maintain
      or increase muscle mass, strength and volume, reduce time in mechanical
      ventilation and weaning time, and increase muscle degradation in critically ill
      patients in ICU. Two studies allowed a meta-analysis of the effects of NMES on
      quadriceps femoris strength and it showed a significant effect in favor of NMES
      in the Medical Research Council (MRC) Scale (standardized mean difference 0.77
      points; p=0.02; 95% CI: 0.13-1.40). CONCLUSIONS: The selected studies showed that
      NMES has good results when used for the maintenance of muscle mass and strength
      in critically ill patients in ICU. Future studies with high methodological
      quality should be conducted to provide more evidence for the use of NMES in an
      ICU setting.

PMID- 25060512
TI  - A systematic review and meta-analysis of ketamine for the prevention of
      persistent post-surgical pain.
AB  - While post-operative pain routinely resolves, persistent post-surgical pain
      (PPSP) is common in certain surgeries; it causes disability, lowers quality of
      life and has economic consequences. The objectives of this systematic review and
      meta-analysis were to evaluate the effectiveness of ketamine in reducing the
      prevalence and severity of PPSP and to assess safety associated with its use. We
      searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE
      through December 2012 for articles in any language. We included randomized,
      controlled trials in adults in which ketamine was administered perioperatively
      via any route. Seventeen studies, the majority of which administered ketamine
      intravenously, met all inclusion criteria. The overall risk of developing PPSP
      was not significantly reduced at any time point in the ketamine group vs.
      placebo, nor did comparisons of pain severity scores reach statistical
      significance. Sensitivity analysis of exclusively intravenous ketamine studies
      included in this meta-analysis demonstrated statistically significant reductions
      in risk of developing PPSP at 3 and 6 months (P = 0.01 and P = 0.04,
      respectively). Adverse event rates were similar between ketamine and placebo
      groups. The study data from our review are heterogeneous and demonstrate efficacy
      of intravenously administered ketamine only in comparison with placebo. Highly
      variable timing and dosing of ketamine in these studies suggest that no unifying
      effective regimen has emerged. Future research should focus on clinically
      relevant outcomes, should stratify patients with pre-existing pain and possible
      central sensitization and should enroll sufficiently large numbers to account for
      loss to follow-up in long-term studies. 

PMID- 25060513
TI  - The treatment of penile carcinoma in situ (CIS) within a UK supra-regional
      network.
AB  - OBJECTIVES: To review outcomes of the treatment of carcinoma in situ (CIS) of the
      penis at a large supra-regional penile cancer network, where centralisation has
      permitted greater experience with treatment outcomes, and suggest treatment
      strategies. PATIENTS AND METHODS: The network penile cancer database, which
      details presentation, treatment and complications was analysed from 2003 to 2010,
      identifying patients with CIS, with a minimum follow-up of 2 years, looking at
      treatments administered and outcomes. RESULTS: In all, 57 patients with mean
      (range) age of 61 (34-91) years were identified. In all, 18 were treated by
      circumcision only, 20 by circumcision and local excision (LE) and 19 by
      circumcision and 5-flurouracil (5-FU). The mean (range) follow-up was 3.5 (2-8)
      years. Of those treated by circumcision none subsequently developed CIS on the
      glans. For those who underwent circumcision + LE, five of 20 (25%) developed
      recurrence requiring further treatment. Of those treated by circumcision + 5-FU,
      14/19 (73.7%) completely responded. Of the five incomplete responders, two had
      focal invasive malignancy at repeat biopsy. One incomplete responder underwent
      glansectomy and four grafting. No complete responders relapsed. Complications of
      5-FU included significant inflammatory response in seven (36.8%), with two
      requiring hospital admission and one neo-phimosis (5.3%). CONCLUSION: This study
      suggests that patients undergoing circumcision for isolated CIS and complete
      responders to 5-FU may require only short-term follow-up, as recurrence is
      unlikely, whereas longer follow up is required for all other patients. However,
      numbers in this study are small and larger studies are needed to support this. An
      incomplete response to 5-FU dictates immediate re-biopsy, as it carries a
      significant chance of previously undetected invasive disease.

PMID- 25060514
TI  - Assessing new developments in the pre-market regulatory process of medical
      devices in the People's Republic of China.
AB  - The objective of this paper is to provide a systematic overview of the Chinese
      medical device registration processes, identify challenges and suggest how these
      can be addressed. In addition, the paper will outline the impact of new policies
      and regulations since the restructuring of the China FDA. A systematic review was
      performed for journal articles between the year of 2009 and 2013 in the following
      databases: PubMed, ScienceDirect and Zhongguozhiwang. The review has identified
      184 papers which were potentially relevant. Seventeen articles were included in
      the review, which highlights the challenges and opportunities related to the
      medical device registration process. In order to understand the actual impact of
      the regulation environment and its policies including the lack of regulatory
      guidance regular assessment updates are crucial. The results of this paper are
      aimed at informing regulatory bodies, health policy decision makers, national and
      international Health Technology Assessment networks as well as medical devices
      manufacturers. 

PMID- 25060515
TI  - The effect of IL-4 and MTHFR gene variants in ankylosing spondylitis.
AB  - PURPOSE: Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic disease
      that characteristically affects the sacroiliac joints and the spine. The exact
      pathogenesis of AS remains poorly understood, but genetic factors play a key role
      in disease development. Several genes have been consistently associated with
      susceptibility to AS. This study was conducted in Turkish AS patients to
      determine the frequency of the methylenetetrahydrofolate reductase (MTHFR) gene
      C677T and interleukin-4 (IL-4) gene 70 bp variable number of tandem repeats
      (VNTR) variants, as well as their association with clinical characteristics.
      METHODS: Genomic DNA obtained from 272 persons (122 AS patients and 150 healthy
      controls) was used in this study. Genomic DNA was isolated and genotyped using a
      polymerase chain reaction (PCR)-based restriction fragment length polymorphism
      (RFLP) assay for the MTHFR C677T and IL-4 70 bp VNTR gene variants, which were
      determined using specific PCR primers. RESULTS: There was statistically
      significant difference between the groups with respect to MTHFR genotype
      distribution (p = 0.02) and allele frequencies (p < 0.001). When we examined
      MTHFR and IL-4 genotype frequencies according to clinical characteristics, we
      found an association between the homozygous MTHFR TT genotype and ocular
      involvement, although this did not reach statistical significance (p = 0.02).
      However, we did not find any difference between the groups with respect to IL-4
      genotype distribution or allele frequencies and clinical characteristics (p >
      0.05). CONCLUSION: Our findings suggest that there is an association of the MTHFR
      gene C677T polymorphism with the susceptibility of a person for development of
      AS. However, the IL-4 gene is not associated with AS within the same population.

PMID- 25060516
TI  - Meta-analysis of functional MBL polymorphisms. Associations with rheumatoid
      arthritis and primary Sjogren's syndrome.
AB  - OBJECTIVE: The aim of this study was to determine whether functional mannose
      binding lectin gene (MBL) polymorphisms are associated with the susceptibility to
      rheumatoid arthritis (RA) or primary Sjogren's syndrome (pSS). METHODS: A meta
      analysis was conducted to investigate the potential association of RA or pSS with
      MBL polymorphisms, including the codon 54 (allele B), codon 57 (allele C), and
      codon 52 (allele D) variants of exon 1, and the - 550 (allele L) and - 221
      (allele X) promoter variants. RESULTS: A total of 12 comparative studies,
      including eight RA (1623 patients and 1671 controls) and four pSS (280 patients
      and 516 controls) studies, were included in the meta-analysis. The meta-analysis
      revealed no association between the MBL B allele and RA in the overall study
      population (odds ratio [OR] 0.991, 95 % confidence interval [CI] 0.726-1.355, p =
      0.957). However, the meta-analysis showed significant associations between the
      MBL D, H, and X alleles and RA in the overall population (OR 1.708, 95 % CI 1.077
      2.707, p = 0.023; OR 1.936, 95 % CI 1.218-3.078, p = 0.005; OR 1.582, 95 % CI
      1.216-2.057, p = 0.001, respectively). An association was found between the MBL B
      allele and pSS in the overall study population (OR 0.691, 95 % CI 0.541-0.917, p
      = 0.010). Stratification by ethnicity indicated a trend toward an association
      between the B allele and pSS in European populations, but no association in Asian
      populations (OR 0.689, 95 % CI 0.465-1.021, p = 0.063; OR 0.896, 95 % CI 0.311
      2.562, p = 0.838, respectively). CONCLUSION: This meta-analysis demonstrated an
      association between the MBL D, L, and X alleles and the risk of RA. It also
      demonstrated an association between the MBL B allele and the susceptibility to
      pSS, suggesting a protective role of the MBL B allele against the development of
      pSS.

PMID- 25060517
TI  - Meta-analysis of the association between functional MICA-TM polymorphisms and
      systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis.
AB  - OBJECTIVE: The aim of this study was to determine whether the major
      histocompatibility complex class I chain-related gene A transmembrane (MICA-TM)
      polymorphism is associated with susceptibility to systemic lupus erythematous
      (SLE), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: A meta
      analysis was conducted to establish the association between MICA-TM polymorphisms
      and SLE, RA and AS in the overall study population, as well as in each ethnic
      group. RESULTS: A total of 13 comparison studies, including five SLE (1601
      patients; 1846 controls), four RA (701 patients; 887 controls) and four AS (346
      patients; 356 controls) studies were considered in the meta-analysis. An
      association between the MICA-TM A5.1 allele and SLE was demonstrated in Europeans
      but not in Asians: odds ratio (OR) = 1.699, 95 % confidence interval (CI) = 1.123
      2.569, p = 0.012 and OR = 0.949, 95 % CI = 0.502-1.793, p = 0.871, respectively.
      However, no association was found in Europeans after Bonferroni correction
      (pcorrected = 0.060). An association was found between the MICA-TM A9 allele and
      RA in Asians (OR = 0.527, 95 % CI = 0.408-0.681, p = 8.9 * 10(-7)) but not in
      Europeans; the association in Asians remained significant after Bonferroni
      correction (pcorrected = 4.5 * 10(-6)). An association between the MICA-TM A4
      phenotype and AS was observed in European and Asian populations (OR = 12.87, 95 %
      CI = 6.747-24.58, p < 1.0 * 10(-9) and OR = 9.461, 95 % CI = 5.754-15.55, p < 1.0
      * 10(-9), respectively). Meta-analysis stratified by human leukocyte antigen
      (HLA)-B27 status revealed an association between the MICA-TM A4 phenotype and HLA
      B27 positivity AS in Asians, but not in Europeans (OR = 0.318, 95 % CI = 0.102
      0.995, p = 0.049 and OR = 2.080, 95 % CI = 0.422-10.25, p = 0.368, respectively).
      However, the association in Asians was not significant after Bonferroni
      correction (pcorrected = 0.245). CONCLUSION: This meta-analysis demonstrated that
      there was no association between MICA-TM polymorphisms and SLE susceptibility,
      but that the MICA-TM A9 allele was associated with an RA risk in Asians.
      Moreover, the association between the MICA-TM A4 phenotype and AS was HLA-B27
      dependent.

PMID- 25060518
TI  - FLT3 kinase inhibitor TTT-3002 overcomes both activating and drug resistance
      mutations in FLT3 in acute myeloid leukemia.
AB  - There have been a number of clinical trials testing the efficacy of FMS-like
      tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) in patients with acute
      myeloid leukemia (AML) harboring a constitutively activating mutation in FLT3.
      However, there has been limited efficacy, most often because of inadequate
      achievement of FLT3 inhibition through a variety of mechanisms. In a previous
      study, TTT-3002 was identified as a novel FLT3 inhibitor with the most potent
      activity to date against FLT3 internal tandem duplication (FLT3/ITD) mutations.
      Here, the activity of TTT-3002 is demonstrated against a broad spectrum of FLT3
      activating point mutations, including the most frequently occurring D835
      mutations. The compound is also active against a number of point mutations
      selected for in FLT3/ITD alleles that confer resistance to other TKIs, including
      the F691L gatekeeper mutation. TTT-3002 maintains activity against patients with
      relapsed AML samples that are resistant to sorafenib and AC220. Studies utilizing
      human plasma samples from healthy donors and patients with AML indicate that TTT
      3002 is only moderately protein bound compared with several other TKIs currently
      in clinical trials. Tumor burden of mice in a FLT3 TKI-resistant transplant model
      is significantly improved by oral dosing of TTT-3002. Therefore, TTT-3002 has
      demonstrated preclinical potential as a promising new FLT3 TKI that may overcome
      some of the limitations of other TKIs in the treatment of FLT3-mutant AML. Cancer
      Res; 74(18); 5206-17. (c)2014 AACR. 

PMID- 25060519
TI  - Armed oncolytic virus enhances immune functions of chimeric antigen receptor
      modified T cells in solid tumors.
AB  - The clinical efficacy of chimeric antigen receptor (CAR)-redirected T cells
      remains marginal in solid tumors compared with leukemias. Failures have been
      attributed to insufficient T-cell migration and to the highly immunosuppressive
      milieu of solid tumors. To overcome these obstacles, we have combined CAR-T cells
      with an oncolytic virus armed with the chemokine RANTES and the cytokine IL15,
      reasoning that the modified oncolytic virus will both have a direct lytic effect
      on infected malignant cells and facilitate migration and survival of CAR-T cells.
      Using neuroblastoma as a tumor model, we found that the adenovirus Ad5Delta24
      exerted a potent, dose-dependent, cytotoxic effect on tumor cells, whereas CAR-T
      cells specific for the tumor antigen GD2 (GD2.CAR-T cells) were not damaged. When
      used in combination, Ad5Delta24 directly accelerated the caspase pathways in
      tumor cells exposed to CAR-T cells, whereas the intratumoral release of both
      RANTES and IL15 attracted CAR-T cells and promoted their local survival,
      respectively, increasing the overall survival of tumor-bearing mice. These
      preclinical data support the use of this innovative biologic platform of
      immunotherapy for solid tumors. Cancer Res; 74(18); 5195-205. (c)2014 AACR. 

PMID- 25060520
TI  - Neutralizing murine TGFbetaR2 promotes a differentiated tumor cell phenotype and
      inhibits pancreatic cancer metastasis.
AB  - Elevated levels of TGFbeta are a negative prognostic indicator for patients
      diagnosed with pancreatic cancer; as a result, the TGFbeta pathway is an
      attractive target for therapy. However, clinical application of pharmacologic
      inhibition of TGFbeta remains challenging because TGFbeta has tumor suppressor
      functions in many epithelial malignancies, including pancreatic cancer. In fact,
      direct neutralization of TGFbeta promotes tumor progression of genetic murine
      models of pancreatic cancer. Here, we report that neutralizing the activity of
      murine TGFbeta receptor 2 using a monoclonal antibody (2G8) has potent
      antimetastatic activity in orthotopic human tumor xenografts, syngeneic tumors,
      and a genetic model of pancreatic cancer. 2G8 reduced activated fibroblasts,
      collagen deposition, microvessel density, and vascular function. These stromal
      specific changes resulted in tumor cell epithelial differentiation and a potent
      reduction in metastases. We conclude that TGFbeta signaling within stromal cells
      participates directly in tumor cell phenotype and pancreatic cancer progression.
      Thus, strategies that inhibit TGFbeta-dependent effector functions of stromal
      cells could be efficacious for the therapy of pancreatic tumors. Cancer Res;
      74(18); 4996-5007. (c)2014 AACR. 

PMID- 25060521
TI  - Obesity, cholesterol metabolism, and breast cancer pathogenesis.
AB  - Obesity and altered lipid metabolism are risk factors for breast cancer in pre-
      and post-menopausal women. These pathologic relationships have been attributed in
      part to the impact of cholesterol on the biophysical properties of cell membranes
      and to the influence of these changes on signaling events initiated at the
      membrane. However, more recent studies have indicated that the oxysterol 27
      hydroxycholesterol (27HC), and not cholesterol per se, may be the primary
      biochemical link between lipid metabolism and cancer. The enzyme responsible for
      production of 27HC from cholesterol, CYP27A1, is expressed primarily in the liver
      and in macrophages. In addition, significantly elevated expression of this enzyme
      within breast tumors has also been observed. It is believed that 27HC, acting
      through the liver X receptor in macrophages and possibly other cells, is involved
      in maintaining organismal cholesterol homeostasis. It has also been shown
      recently that 27HC is an estrogen receptor agonist in breast cancer cells and
      that it stimulates the growth and metastasis of tumors in several models of
      breast cancer. These findings provide the rationale for the clinical evaluation
      of pharmaceutical approaches that interfere with cholesterol/27HC synthesis as a
      means to mitigate the impact of cholesterol on breast cancer pathogenesis. Cancer
      Res; 74(18); 4976-82. (c)2014 AACR. 

PMID- 25060522
TI  - ADAM9 promotes lung cancer metastases to brain by a plasminogen activator-based
      pathway.
AB  - The transmembrane cell adhesion protein ADAM9 has been implicated in cancer cell
      migration and lung cancer metastasis to the brain, but the underpinning
      mechanisms are unclear and clinical support has been lacking. Here, we
      demonstrate that ADAM9 enhances the ability of tissue plasminogen activator (tPA)
      to cleave and stimulate the function of the promigratory protein CDCP1 to promote
      lung metastasis. Blocking this mechanism of cancer cell migration prolonged
      survival in tumor-bearing mice and cooperated with dexamethasone and dasatinib (a
      dual Src/Abl kinase inhibitor) treatment to enhance cytotoxic treatment. In
      clinical specimens, high levels of ADAM9 and CDCP1 correlated with poor prognosis
      and high risk of mortality in patients with lung cancer. Moreover, ADAM9 levels
      in brain metastases derived from lung tumors were relatively higher than the
      levels observed in primary lung tumors. Our results show how ADAM9 regulates lung
      cancer metastasis to the brain by facilitating the tPA-mediated cleavage of
      CDCP1, with potential implications to target this network as a strategy to
      prevent or treat brain metastatic disease.

PMID- 25060523
TI  - Habitus of home and traditional drinking: a qualitative analysis of reported
      middle-class alcohol use.
AB  - There is evidence that alcohol consumption among those in middle-class
      occupations consistently exceeds safe levels, yet there has been little research
      into why this occurs. This article explores the meanings associated with alcohol
      use among professional, managerial and clerical workers. Qualitative data were
      collected from five focus groups of male and female employees aged 21-55 (N =49:
      32 male, 17 female). Each focus group was conducted on the premises of a medium
      scale or large-scale employer, four public sector and one private sector, in the
      north-east of England. Using Bourdieu's concepts of 'habitus', 'capitals' and
      'fields' we found that, among these middle-class occupational groups, alcohol use
      was associated with two habitus: a 'home drinking' habitus and a 'traditional
      drinking' habitus. Those of the home drinking habitus particularly used wine as a
      source of cultural capital and a means of distinction, whereas those in the
      traditional habitus consumed lager, beer and spirits to have fun in social
      settings. A small minority appeared to belong to a third, omnivorous, habitus
      where a wide range of alcoholic drinks were consumed in a variety of contexts.
      Existing public health initiatives to reduce alcohol consumption may require
      modification to accommodate a range of drinking cultures. 

PMID- 25060524
TI  - Hydrostatic pressure-driven three-dimensional cartilage induction using human
      adipose-derived stem cells and collagen gels.
AB  - BACKGROUND: The chondrogenic potential of adipose-derived stem cells (ASCs) has
      been previously demonstrated, although several reports have indicated that ASCs
      produce less cartilage-specific matrix than bone marrow-derived mesenchymal stem
      cells. In this study, we intended to improve chondrogenic phenotypes of ASCs
      using hydrostatic pressure (HP), without utilizing any growth factors other than
      the transforming growth factor-beta1. METHODS: Human ASCs (CD13(+), 44(+), 90(+),
      14(-), 31(-), 34(-)) were harvested and cultured. After three passages, the cells
      were suspended in 0.3% neutralized collagen type I solution and injected into
      semipermeable membrane tubes, from which 66 pouches were constructed. After a day
      of incubation, the 66 pouches were divided into three groups. Group HP1: Pouches
      were incubated for 1 week with treatment of cyclic HP at 0-0.5 MPa (4.93 atm),
      0.5 Hz, with a medium replenishment rate of 0.1 mL/min at 37 degrees C, 3% O2,
      and 5% CO2 in air using a bioprocessor. This was followed by 3 weeks with no HP
      and without pouches. Group HP2: Pouches were incubated for the first and third
      week (2 total weeks) with the same condition of Group HP1. No HP was applied in
      the second and fourth week. Group AP: Pouches with one end opened were incubated
      without HP. We evaluated the cell constructs histologically and
      immunohistochemically, as well as for specific gene expression. RESULTS:
      Accumulation of the matrix in the HP1 and HP2 groups was much denser than AP
      groups, particularly after 2 weeks. Cell numbers in the HP groups increased
      gradually in the middle zone and peaked at 1 week after incubation, maintaining
      their numbers for the entire course on the surface layer of the construct. In the
      genomic study results, COL 2A1, COL 10A1, ACAN, SOX9, MMP3, and MMP13 were
      upregulated and COL 1A1, ITGB1, and PCNA were downregulated by HP. There were no
      significant differences between HP1 and HP2 gene expression. CONCLUSION: It was
      suggested that HP is especially beneficial in the early stage of chondrogenesis
      of ASCs. Moreover, the expression profile of genes related to chondrocyte
      differentiation/proliferation was significantly enhanced by HP loading compared
      with the AP control.

PMID- 25060525
TI  - Lip reading without awareness.

PMID- 25060526
TI  - 1H and 13C assignments of three series bioactive imidazo[2,1-b]thiazole
      derivatives.

PMID- 25060527
TI  - Clinical impact of ABCC1 and ABCC2 genotypes and haplotypes in mediating imatinib
      resistance among chronic myeloid leukaemia patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: The introduction and success of imatinib mesylate
      (IM) has brought about a paradigm shift in chronic myeloid leukaemia (CML)
      treatment. However, despite the high efficacy of IM, clinical resistance develops
      due to a heterogeneous array of mechanisms. Pharmacogenetic variability as a
      result of genetic polymorphisms could be one of the most important factors
      influencing resistance to IM. The aim of this study was to investigate the
      association between genetic variations in drug efflux transporter ABCC1 (MRP1)
      and ABCC2 (MRP2) genes and response to IM in patients with CML. METHODS: We
      genotyped 215 Malaysian patients with CML (comprising of two groups with 108 IM
      resistant and 107 IM responsive) for polymorphisms of ABCC1 (2012G>T and 2168G>A)
      and ABCC2 (-24C>T, 1249G>A and 3972C>T) genes. Genotype, allele and haplotype
      frequencies were compared between two groups of patients. Patients with CML were
      further stratified according to their clinical response to IM into those having
      cytogenetics and molecular responses, and the associations with genotypes were
      evaluated. RESULTS AND DISCUSSION: We observed no significant differences in the
      distribution of any of the tested genotypes between the investigated groups.
      However, on evaluating the risk association, ABCC2 T-24 G1249 T3972 haplotype was
      found to be associated with IM resistance (P = 0.046). These results suggest that
      haplotype variants -24T and 3972T might be associated with lower expression of
      ABCC2 protein and reduced transport activity and hence might be contributing to
      development of IM resistance. WHAT IS NEW AND CONCLUSION: Our results suggest the
      ABCC2 T-24 G1249 T3972 haplotype was associated with imatinib resistance.
      However, the evidence is as yet insufficient to establish this haplotype as a
      predictive biomarker for response to the drug.

PMID- 25060528
TI  - Intracranial pathway for dermal lymphatic drainage.

PMID- 25060529
TI  - Structural variants of yeast prions show conformer-specific requirements for
      chaperone activity.
AB  - Molecular chaperones monitor protein homeostasis and defend against the
      misfolding and aggregation of proteins that is associated with protein
      conformational disorders. In these diseases, a variety of different aggregate
      structures can form. These are called prion strains, or variants, in prion
      diseases, and cause variation in disease pathogenesis. Here, we use variants of
      the yeast prions [RNQ+] and [PSI+] to explore the interactions of chaperones with
      distinct aggregate structures. We found that prion variants show striking
      variation in their relationship with Hsp40s. Specifically, the yeast Hsp40 Sis1
      and its human orthologue Hdj1 had differential capacities to process prion
      variants, suggesting that Hsp40 selectivity has likely changed through evolution.
      We further show that such selectivity involves different domains of Sis1, with
      some prion conformers having a greater dependence on particular Hsp40 domains.
      Moreover, [PSI+] variants were more sensitive to certain alterations in Hsp70
      activity as compared to [RNQ+] variants. Collectively, our data indicate that
      distinct chaperone machinery is required, or has differential capacity, to
      process different aggregate structures. Elucidating the intricacies of chaperone
      client interactions, and how these are altered by particular client structures,
      will be crucial to understanding how this system can go awry in disease and
      contribute to pathological variation. 

PMID- 25060531
TI  - Peripheral artery disease in patients with type 2 diabetes.

PMID- 25060530
TI  - Cystic fibrosis related diabetes--a new perspective on the optimal management of
      postprandial glycemia.
AB  - As the average life expectancy of patients with cystic fibrosis (CF) improves,
      the long term co-morbidities assume increasing importance. CF related diabetes
      (CFRD) has adverse effects on both nutrition and pulmonary function, and is
      associated with increased mortality. Abnormalities of glucose metabolism in CF
      represent a continuum; however the predominant abnormality is postprandial, not
      pre-prandial, glycemia. Insulin is currently recommended as the treatment of
      choice for CFRD, but its use is associated with a number of limitations,
      including hypoglycemia. Both the rate of gastric emptying and the consequent
      release of the 'incretin' hormones, glucose-dependent insulinotropic polypeptide
      (GIP) and glucagon-like-peptide-1 (GLP-1), from the gut are important
      determinants of overall glycemic control, particularly postprandial glycemia.
      Both are abnormal in conditions associated with exocrine pancreatic
      insufficiency. Incretin based therapies that have the capacity to slow gastric
      emptying and/or modulate the release of 'incretin' hormones, are now used widely
      in type 2 diabetes (T2D). This paper explores the determinants of glycemic
      control in CF, with a particular focus on the roles of gastric emptying and
      'incretin' hormones, providing a rationale for the use of therapies that delay
      gastric emptying, including incretin mimetics, to minimize postprandial glycemia
      and improve nutritional status. 

PMID- 25060532
TI  - Genotype-guided drug prescribing: a systematic review and meta-analysis of
      randomized control trials.
AB  - AIM: Adverse drug events lead to increased morbidity, mortality and health care
      costs. Pharmacogenetic testing that guides drug prescribing has the potential to
      reduced adverse drug events and increase drug effectiveness. Our aim was to
      quantify the clinical effectiveness of genotype-guided prescribing. METHODS:
      Three electronic databases were searched from January 1980 through December 2013.
      Studies were eligible if they were RCTs comparing genotype-guided prescribing
      with non-genetic informed prescribing, reported drug specific adverse drug events
      and clinical effectiveness outcomes. Two reviewers independently screened titles
      and abstracts, extracted data and assessed study quality. Meta-analyses of
      specific outcomes were conducted where data allowed. RESULTS: Fifteen studies,
      involving 5688 patients and 19 drugs, met the inclusion and exclusion criteria.
      Eight studies had statistically significant results for their primary outcome in
      favour of genotype-guided prescribing. Nine studies evaluated genotype-guided
      warfarin dosing. Analysis of percentage of time in therapeutic international
      normalized ratio range (1952 individuals) showed a statistically significant
      benefit in favour of genotype-guided warfarin dosing (mean difference = 6.67; 95%
      CI 1.34, 12.0, I(2) = 80%). There was a statistically significant reduction in
      numbers of warfarin-related minor bleeding, major bleeding and thromboembolisms
      associated with genotype guided warfarin dosing, relative risk 0.57 (95% CI 0.33,
      0.99; I(2) = 60%). It was not possible to meta-analyze genotype-guided dosing for
      other drugs. Of the six non-warfarin genotype-guided trials, two demonstrated a
      statistically significant benefit for their primary outcome, odds ratio 0.03 (95%
      CI 0.00, 0.62, P < 0.001) for abacavir. CONCLUSIONS: There is evidence of
      improved clinical effectiveness associated with genotype-guided warfarin dosing.

PMID- 25060533
TI  - [Atypical presentation of a treatment-resistant "forehead skin furuncle"].

PMID- 25060535
TI  - Mechanism of aggregate formation in simplified industrial silica styrene
      butadiene nanocomposites: effect of chain mass and grafting on rheology and
      structure.
AB  - The formation of aggregates in simplified industrial styrene-butadiene
      nanocomposites with silica filler has been studied using a recent model based on
      a combination of electron microscopy, computer simulations, and small-angle X-ray
      scattering. The influence of the chain mass (40 to 280 kg mol(-1), PI < 1.1),
      which sets the linear rheology of the samples, was investigated for a low (9.5
      vol%) and high (19 vol%) silica volume fraction. 50% of the chains bear a single
      graftable end-group, and it is shown that the (chain-mass dependent) grafting
      density is the structure-determining parameter. A model unifying all available
      data on this system is proposed and used to determine a critical aggregate
      grafting density. The latter is found to be closely related to the mushroom-to
      brush transition of the grafted layer. To our best knowledge, this is the first
      comprehensive evidence for the control of the complex nanoparticle aggregate
      structure in nanocomposites of industrial relevance by the physical parameters of
      the grafted layer. 

PMID- 25060534
TI  - Incorporating gene-environment interaction in testing for association with rare
      genetic variants.
AB  - OBJECTIVES: The incorporation of gene-environment interactions could improve the
      ability to detect genetic associations with complex traits. For common genetic
      variants, single-marker interaction tests and joint tests of genetic main effects
      and gene-environment interaction have been well-established and used to identify
      novel association loci for complex diseases and continuous traits. For rare
      genetic variants, however, single-marker tests are severely underpowered due to
      the low minor allele frequency, and only a few gene-environment interaction tests
      have been developed. We aimed at developing powerful and computationally
      efficient tests for gene-environment interaction with rare variants. METHODS: In
      this paper, we propose interaction and joint tests for testing gene-environment
      interaction of rare genetic variants. Our approach is a generalization of
      existing gene-environment interaction tests for multiple genetic variants under
      certain conditions. RESULTS: We show in our simulation studies that our
      interaction and joint tests have correct type I errors, and that the joint test
      is a powerful approach for testing genetic association, allowing for gene
      environment interaction. We also illustrate our approach in a real data example
      from the Framingham Heart Study. CONCLUSION: Our approach can be applied to both
      binary and continuous traits, it is powerful and computationally efficient.

PMID- 25060536
TI  - A new texture and shape based technique for improving meningioma classification.
AB  - Over the past decade, computer-aided diagnosis is rapidly growing due to the
      availability of patient data, sophisticated image acquisition tools and
      advancement in image processing and machine learning algorithms. Meningiomas are
      the tumors of brain and spinal cord. They account for 20% of all the brain
      tumors. Meningioma subtype classification involves the classification of benign
      meningioma into four major subtypes: meningothelial, fibroblastic, transitional,
      and psammomatous. Under the microscope, the histology images of these four
      subtypes show a variety of textural and structural characteristics. High
      intraclass and low interclass variabilities in meningioma subtypes make it an
      extremely complex classification problem. A number of techniques have been
      proposed for meningioma subtype classification with varying performances on
      different subtypes. Most of these techniques employed wavelet packet transforms
      for textural features extraction and analysis of meningioma histology images. In
      this article, a hybrid classification technique based on texture and shape
      characteristics is proposed for the classification of meningioma subtypes.
      Meningothelial and fibroblastic subtypes are classified on the basis of nuclei
      shapes while grey-level co-occurrence matrix textural features are used to train
      a multilayer perceptron for the classification of transitional and psammomatous
      subtypes. On the whole, average classification accuracy of 92.50% is achieved
      through the proposed hybrid classifier; which to the best of our knowledge is the
      highest.

PMID- 25060537
TI  - From the era of genome analysis to the era of genomic drug discovery: a
      pioneering example of rheumatoid arthritis.
AB  - Although we have obtained comprehensive catalogs of genetic risk loci that are
      linked to human diseases, little is known regarding how to devise a systematic
      strategy to integrate genetic study results with diverse biological resources.
      Such strategies will be crucial for providing novel insights into disease biology
      and for aiding drug discovery as an ultimate goal. Here we describe the current
      progress in this field using a pioneering example of large-scale genetic
      association studies on rheumatoid arthritis (RA), an autoimmune disease
      characterized by inflammation and destruction of joints. Through functional and
      bioinformatic annotations of risk single nucleotide polymorphisms (SNPs) and
      genes from >100 RA risk loci identified by genome-wide association study (GWAS)
      meta-analysis, we found novel biological insights into RA pathogenicity. Further,
      by integrating RA genetic findings with the complete catalog of approved drugs
      for RA and other diseases, we provide empirical data to indicate that human
      genetic-based approaches may be useful for supporting 'genetics-driven genomic
      drug discovery' efforts in complex human traits and suggest that further
      development of integrative approaches should be undertaken. 

PMID- 25060538
TI  - Lessons learned from mice deficient in lectin complement pathway molecules.
AB  - The lectin pathway of the complement system is initiated when the pattern
      recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11,
      bind to invading pathogens or damaged host cells. This leads to activation of
      MBL/ficolin/collectin-11 associated serine proteases (MASPs), which in turn
      activate downstream complement components, ultimately leading to elimination of
      the pathogen. Mice deficient in the key molecules of lectin pathway of complement
      have been generated in order to build knowledge of the molecular mechanisms of
      the lectin pathway in health and disease. Despite differences in the genetic
      arrangements of murine and human orthologues of lectin pathway molecules, the
      knockout mice have proven to be valuable models to explore the effect of
      deficiency states in humans. In addition, new insight and unexpected findings on
      the diverse roles of lectin pathway molecules in complement activation, pathogen
      infection, coagulation, host tissue injury and developmental biology have been
      revealed by in vivo investigations. This review provides an overview of the mice
      deficient in lectin pathway molecules and highlights some of the most important
      findings that have resulted from studies of these. 

PMID- 25060539
TI  - Sclerosing cholangitis with thumbprint appearance and incomplete steroid
      response.

PMID- 25060540
TI  - Recurring DNA copy number gain at chromosome 9p13 plays a role in the activation
      of multiple candidate oncogenes in progressing oral premalignant lesions.
AB  - Genomic alteration at chromosome 9p has been previously reported as a frequent
      and critical event in oral premalignancy. While this alteration is typically
      reported as a loss driven by selection for CDKN2A deactivation (at 9p21.3), we
      detect a recurrent DNA copy number gain of ~2.49 Mbp at chromosome 9p13 in oral
      premalignant lesions (OPLs) that later progressed to invasive lesions. This
      recurrent alteration event has been validated using fluorescence in situ
      hybridization in an independent set of OPLs. Analysis of publicly available gene
      expression datasets aided in identifying three oncogene candidates that may have
      driven selection for DNA copy number increases in this region (VCP, DCTN3, and
      STOML2). We performed in vitro silencing and activation experiments for each of
      these genes in oral cancer cell lines and found that each gene is independently
      capable of upregulating proliferation and anchorage-independent growth. We next
      analyzed the activity of each of these genes in biopsies of varying histological
      grades that were obtained from a diseased oral tissue field in a single patient,
      finding further molecular evidence of parallel activation of VCP, DCTN3, and
      STOML2 during progression from normal healthy tissue to invasive oral carcinoma.
      Our results support the conclusion that DNA gain at 9p13 is important to the
      earliest stages of oral tumorigenesis and that this alteration event likely
      contributes to the activation of multiple oncogene candidates capable of
      governing oral cancer phenotypes. 

PMID- 25060541
TI  - A randomized study of formoterol fumarate in a porous particle metered-dose
      inhaler in patients with moderate-to-severe COPD.
AB  - BACKGROUND: Formoterol fumarate (FF) is a well-established long-acting beta2
      agonist. This represents the first clinical study of FF in a metered-dose inhaler
      (FF MDI) based on proprietary lipid-based porous-particle engineering technology.
      METHODS: In this randomized, double-blind, 5-period, crossover study
      (NCT00880490), subjects received 2.4, 4.8, and 9.6 MUg of FF MDI, open-label
      Foradil((r)) Aerolizer((r)) (FA) 12 MUg, and placebo. Spirometry was performed at
      baseline, 15 and 30 min, and 1, 2, 4, 6, 8, 10, 11.5, and 12 h post-dose.
      RESULTS: Thirty-four subjects were enrolled. Improvement in forced expiratory
      volume in 1 s (FEV1) was similar between FF MDI 9.6 MUg and FA. Change in FEV1
      area under the curve for 0-12 h (AUC0-12) for each FF MDI dose demonstrated
      superior efficacy versus placebo (P < .001 for all 3 doses). Over 12 h and at
      each time point, FF MDI 9.6 MUg was non-inferior to FA for FEV1 AUC0-12 with the
      95% CI's supporting a maximum difference of approximately 45 mL. Peak and trough
      FEV1, forced vital capacity, peak expiratory flow rate, peak inspiratory
      capacity, and pharmacokinetics confirmed the primary endpoint, with dose ordering
      of the FF MDI 2.4, 4.8, and 9.6 MUg, and comparability of FF MDI 9.6 MUg to FA.
      All 3 doses of FF MDI were safe and well-tolerated, with a safety profile similar
      to that of placebo and FA. CONCLUSIONS: The efficacy and pharmacokinetic profile
      of FF MDI 9.6 MUg were comparable to FA 12 MUg and with similar safety to placebo
      and FA. TRIAL REGISTRATION: This clinical trial was registered on
      ClinicalTrials.gov, Identifier: NCT NCT00880490.

PMID- 25060542
TI  - Systemic corticosteroids for the treatment of asthma exacerbations during and
      outside of pregnancy in an acute-care setting.
AB  - BACKGROUND: Asthma exacerbations are common during pregnancy with a prevalence as
      high as 51.9% among women with severe asthma. OBJECTIVE: To compare the treatment
      of asthma exacerbations in an acute-care setting during and outside of pregnancy.
      METHODS: We formed a cohort of women who sought medical care for an asthma
      exacerbation at a teaching hospital during or in the year preceding pregnancy,
      between 1998 and 2008. An exacerbation was composed of one or more medical
      encounters in an acute-care setting (hospital-based outpatient clinic, emergency
      department, or during hospitalization). Data were retrieved from medical charts
      and health administrative databases. We compared the use of systemic
      corticosteroids (SCSs) during and outside of pregnancy with a Cox proportional
      hazards model. RESULTS: The cohort was formed of 39 women who had 40
      exacerbations during and 39 exacerbations outside of pregnancy. Use of SCSs to
      treat exacerbations was less frequent (adjusted hazard ratio: 0.51; 95% CI: 0.31
      0.84) during pregnancy. Moreover, upon the first medical encounter related to the
      exacerbation, SCSs, when administered, were given less frequently to women when
      pregnant than when non-pregnant (83% vs. 100%). The SCS prescription was filled
      at the community pharmacy 65% and 67% of the time when it was prescribed at
      discharge to women when pregnant than when non-pregnant, respectively.
      CONCLUSION: We observed a reduced and delayed use of SCSs for the treatment of
      asthma exacerbations in women when pregnant than when non-pregnant, with similar
      numbers of women in both conditions filling their SCSs prescription in
      pharmacies.

PMID- 25060543
TI  - Esse est percipi: a neurophilosophical model of psychosis.
AB  - Philosophers, psychiatrists and neuroscientists have all expressed interest in
      and formulated hypotheses on the nature of hallucinations, but no sufficient
      integration of these models exists to this date. The objective of this article is
      to present a neurophilosophical model of psychosis linking the neurobiology with
      the phenomenology of hallucinations and delusions. It is proposed that psychotic
      hallucinations could be regarded as 'intrusions' of subjective idealism, a
      condition where reality is mind dependent, into realism, a condition where
      reality is mind independent. Furthermore, delusions would be an attempt by the
      person to make sense of these intrusions. This approach is supported by
      phenomenological evidence of increased self-relatedness in hallucinations and
      delusions, and by current neurobiological evidence on the role of the reward
      system, default mode network and corollary discharge circuit in positive
      symptomatology. This model has clinical, research and therapeutic implications,
      and also demonstrates how scientific results can be informed and enhanced by
      philosophical theories and vice versa.

PMID- 25060544
TI  - Impact of behavioral genetic evidence on the perceptions and dispositions of
      child abuse victims.
AB  - BACKGROUND: Behavioral genetic research is beginning to elucidate some of the
      genetic contributions to human behaviors - including criminal and other
      problematic behaviors - and their interactions with environmental influences. One
      of the most studied of these interactions involves low-activity alleles of the
      monoamine oxidase A (MAOA) gene, which appear to increase the risk of antisocial
      behavior among males in the wake of childhood maltreatment. Some scholars have
      suggested that decisions about disposition of child abuse victims should be
      shaped by these findings, but the extent of public support for such approaches
      has not been assessed. METHODS: In this study, a representative sample of the US
      population (n = 250) was presented with a vignette about a child, physically
      abused by his mother, who was tested for the presence of an allele that increases
      the risk of future impulsive violent behavior. Participants were asked about
      their views regarding the child's disposition, including return to his mother,
      and medical or psychological treatment. RESULTS: Although participants thought
      that genetic data should be taken into account, the presence of an allele that
      increases the risk of impulsive violent behavior did not affect views regarding
      the child's return to his mother. However, it did increase respondents'
      willingness to provide the child with medical treatment and their view of the
      child as dangerous to other children. CONCLUSIONS: The findings suggest that
      behavioral genetic evidence has effects on perceptions of dangerousness and
      tendencies to view problems as medical but that the public is cautious about the
      use of genetic findings in child abuse adjudications.

PMID- 25060545
TI  - High-concentration supplemental perioperative oxygen and surgical site infection
      following elective colorectal surgery for rectal cancer: a prospective,
      randomized, double-blind, controlled, single-site trial.
AB  - BACKGROUND: Perioperative supplemental oxygen has been proposed to decrease the
      incidence of surgical site infection (SSI) in colorectal surgery with
      controversial results. We have assessed the influence of hyperoxygenation on SSI
      by using the most homogeneous study population. METHODS: We studied, in a
      prospective randomized study, 81 patients, who underwent elective open
      infraperitoneal anastomosis for rectal cancer. Patients were assigned randomly to
      an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n = 41)
      or 80% (n = 40). Administration was commenced after induction of anesthesia and
      maintained for 6 hours after surgery. RESULTS: The overall wound infection rate
      was 21%: 11 patients (26.8%) had wound infections in the 30% FiO2 group and 6
      (15%) in the 80% FiO2 group (P < .05). The risk of SSI was 41% lower in the 80%
      FiO2 group. CONCLUSION: Supplemental 80% FiO2 reduced postoperative SSI with few
      risks to the patient and little associated cost.

PMID- 25060546
TI  - Nanoelectrode for amperometric monitoring of individual vesicular exocytosis
      inside single synapses.
AB  - Chemical neurotransmission occurs at chemical synapses and endocrine glands, but
      up to now there was no means for direct monitoring of neurotransmitter exocytosis
      fluxes and their precise kinetics from inside an individual synapse. The
      fabrication of a novel finite conical nanoelectrode is reported perfectly suited
      in size and electrochemical properties for probing amperometrically inside what
      appears to be single synapses and monitoring individual vesicular exocytotic
      events in real time. This allowed obtaining direct and important physiological
      evidences which may yield important and new insights into the nature of synaptic
      communications. 

PMID- 25060547
TI  - A private affair: children's experiences prior to colonoscopy.
AB  - AIMS AND OBJECTIVES: To illuminate children's experiences prior to colonoscopy.
      BACKGROUND: It is well known that children need to be well prepared before
      undergoing stressful medical procedures, and the goal of such preparations should
      focus on minimising their level of anxiety. The clinical investigation of
      children with suspected inflammatory bowel disease involves several steps, with
      colonoscopy being routinely used to investigate the colon and the lower part of
      the small intestine. To minimise children's anxiety during various medical
      procedures, it is important that information about their experiences is obtained
      directly from the children themselves. DESIGN: A qualitative study. METHOD: The
      study was designed as a qualitative interview study involving 17 children aged 10
      17 years undergoing colonoscopy at a children's university hospital in Sweden.
      Verbatim transcripts were analysed using content analysis. RESULTS: The
      children's experiences prior to colonoscopy were identified as belonging to an
      overall theme, a private affair, and to four categories: preparing yourself,
      mastering the situation, reluctantly participating and feeling emotional support.
      CONCLUSION: This study shows that children's experiences prior to colonoscopy are
      a private affair and that the preparation needs to be individually adapted for
      the 'preprocedural' preparation to be comprehended. RELEVANCE TO CLINICAL
      PRACTICE: The children's experiences ascertained in this study can contribute to
      a greater understanding of children's needs prior to a colonoscopy and may
      provide professional care staff with the basis for future nursing assessments.

PMID- 25060548
TI  - Singing ability is rooted in vocal-motor control of pitch.
AB  - The inability to vocally match a pitch can be caused by poor pitch perception or
      by poor vocal-motor control. Although previous studies have tried to examine the
      relationship between pitch perception and vocal production, they have failed to
      control for the timbre of the target to be matched. In the present study, we
      compare pitch-matching accuracy with an unfamiliar instrument (the slider) and
      with the voice, designed such that the slider plays back recordings of the
      participant's own voice. We also measured pitch accuracy in singing a familiar
      melody ("Happy Birthday") to assess the relationship between single-pitch
      matching tasks and melodic singing. Our results showed that participants (all
      nonmusicians) were significantly better at matching recordings of their own
      voices with the slider than with their voice, indicating that vocal-motor control
      is an important limiting factor on singing ability. We also found significant
      correlations between the ability to sing a melody in tune and vocal pitch
      matching, but not pitch matching on the slider. Better melodic singers also
      tended to have higher quality voices (as measured by acoustic variables). These
      results provide important evidence about the role of vocal-motor control in poor
      singing ability and demonstrate that single-pitch-matching tasks can be useful in
      measuring general singing abilities. 

PMID- 25060549
TI  - Metabolic abnormalities and polymorphisms of the vitamin D receptor (VDR) and
      ZNF365 genes in children with urolithiasis.
AB  - Composition of urinary stones in children from Yucatan, Mexico, is calcium and
      uric acid. Polymorphisms in VDR and ZNF365 genes have been associated to calcium
      and uric acid lithiasis, respectively. We evaluated the association of
      polymorphisms TaqI and FokI of VDR gene and Ala62Thr of ZNF365 gene with the
      metabolic disorders (MD) in children with urolithiasis (UL). We included 109
      children with UL. Creatinine, calcium, phosphorus, magnesium, uric acid, oxalates
      and citrates were measured in fresh urine. Urinary indices were calculated for
      determining the MD. VDR and ZNF365 polymorphisms were determined by PCR-RFLP.
      Genotype frequencies were compared with the frequency of MD and with the averages
      of excretion of the analytes, using the statistical package STATA 11.0. The most
      frequent MD were hypocitraturia (35.8 %) and hyperuricosuria (22.9 %). The
      comparison of genotype frequencies with the frequency of MD did not show
      significant differences (p > 0.05). The comparison of the urinary excretion
      averages of analytes with respect to the genotype showed that GG homozygotes have
      higher concentrations of uric acid and citrate than AG heterozygotes (p = 0.03),
      and that fF heterozygotes have lower concentrations of citrate (p = 0.009).
      Hypocitraturia and hyperuricosuria were the most common metabolic disorders. The
      frequency of MD is not associated with polymorphisms. However, in children with
      urolithiasis of Yucatan, GG homozygotes excrete higher concentrations of uric
      acid and citrates, and fF heterozygotes have lower concentrations of citrates.

PMID- 25060550
TI  - Resuscitation practices in cardiac surgery.

PMID- 25060551
TI  - Stimulation of colonic motility by oral PEG electrolyte bowel preparation
      assessed by MRI: comparison of split vs single dose.
AB  - BACKGROUND: Most methods of assessing colonic motility are poorly acceptable to
      patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility
      and fluid distributions. We predicted that a dose of oral polyethylene glycol
      (PEG) and electrolyte solution would increase ileo-colonic inflow and stimulate
      colonic motility. We aimed to investigate the colonic response to distension by
      oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of
      single 2 L vs split (2 * 1 L) dosing. METHODS: Twelve HVs received a split dose
      (1 L the evening before and 1 L on the study day) and another 12 HVs a single
      dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans,
      completed symptom questionnaires, and provided stool samples. Outcomes included
      small bowel water content, ascending colon motility index, and regional colonic
      volumes. KEY RESULTS: Small bowel water content increased fourfold from baseline
      after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total
      colonic volume increase from baseline was smaller for the split dose at 35 +/- 8%
      than for the single dose at 102 +/- 27%, p = 0.0332. The ascending colon motility
      index after treatment was twofold higher for the single dose group (p = 0.0103).
      CONCLUSIONS & INFERENCES: Ingestion of 1 and 2 L PEG electrolyte solution caused
      a rapid increase in the small bowel and colonic volumes and a robust rise in
      colonic motility. The increase in both volumes and motility was dose dependent.
      Such a challenge, being well-tolerated, could be a useful way of assessing
      colonic motility in future studies.

PMID- 25060552
TI  - Race/Ethnicity is predictive of lymph node status in patients with early gastric
      cancer.
AB  - BACKGROUND: Race/ethnicity has long been suspected to affect survival in patients
      with gastric adenocarcinoma. However, the clinicohistopathological impact of race
      or ethnicity on early gastric cancer (EGC) is not known. METHODS: From 2000 to
      2013, 286 patients underwent gastrectomy and 104 patients had pathological
      confirmation of EGC. A retrospective analysis of pathological and clinical
      prognostic indicators was performed. RESULTS: The study population consisted of
      38 (37%) Asian Americans and 66 (63%) non-Asian Americans. Of these, 2 (5.3%)
      Asian Americans and 19 (28.8%) non-Asian Americans had pathological confirmation
      of lymph node metastasis (LNM) (p = 0.004). Univariate analysis comparing the
      clinicohistopathological characteristics in each group did not reveal significant
      difference regarding histotype, tumor size, grade, location, morphology, or
      lymphovascular invasion, except for the LNM rate and mean body mass index (23.2
      versus 26.6, p < 0.001). Multivariate analysis showed that non-Asian
      race/ethnicity (odds ratio (OR), 9.09; 95% confidence interval (CI), 1.12-71.43;
      p = 0.038), younger age (OR, 1.11; 95% CI, 1.01-1.12; p = 0.046), and
      lymphovascular invasion (OR, 13.9; 95% CI, 2.40-79.99; p = 0.003) were
      significant predictors for LNM. CONCLUSIONS: This study demonstrated that Asian
      American race in EGC is associated with a significantly decreased rate of LNM in
      comparison to non-Asian Americans, despite similar histopathological
      characteristics of each group.

PMID- 25060553
TI  - Transglutaminase 2 ablation leads to mitophagy impairment associated with a
      metabolic shift towards aerobic glycolysis.
AB  - Macroautophagy selectively degrades dysfunctional mitochondria by a process known
      as mitophagy. Here we demonstrate the involvement of transglutaminase 2 (TG2) in
      the turnover and degradation of damaged mitochondria. In TG2-ablated cells we
      observed the presence of a large number of fragmented mitochondria that display
      decreased membrane potential, downregulation of IF1 along with increased Drp1 and
      PINK1 levels, two key proteins regulating the mitochondrial fission. Of note, we
      demonstrate that in healthy mitochondria, TG2 interacts with the dynamic proteins
      Drp1 and Fis1; interestingly, their interaction is largely reduced upon induction
      of the fission process by carbonyl cyanide m-chlorophenyl hydrazine (CCCP). In
      keeping with these findings, mitochondria lacking TG2 are more susceptible to
      CCCP treatment. As a consequence of accumulation of damaged mitochondria, cells
      lacking TG2 increased their aerobic glycolysis and became sensitive to the
      glycolytic inhibitor 2-deoxy-D-glucose (2-DG). In contrast, TG2-proficient cells
      are more resistant to 2-DG-induced apoptosis as the caspase 3 is inactivated
      through the enzyme's crosslinking activity. The data presented in this study show
      that TG2 plays a key role in cellular dynamics and consequently influences the
      energetic metabolism. 

PMID- 25060554
TI  - Factors influencing women's decisions to drink alcohol during pregnancy: findings
      of a qualitative study with implications for health communication.
AB  - BACKGROUND: Despite Australian guidelines advising abstinence from alcohol during
      pregnancy, a relatively high number of Australian women continue to drink alcohol
      while pregnant. While some call for greater advocacy of the need for abstinence,
      others have expressed concern that abstinence messages may be harmful to pregnant
      women and their unborn babies due to the anxiety they could provoke. We present
      findings on women's deliberations over drinking alcohol during pregnancy,
      particularly their emotional dimensions, to inform debates about public health
      messages and practitioner-patient discussions regarding alcohol use during
      pregnancy. METHODS: Semi-structured face-to-face interviews were conducted with
      40 women in their homes. Our sample comprised women aged 34-39, drawn from the
      Australian Longitudinal Study on Women's Health, living in the Greater Brisbane
      Area who were pregnant, or had recently given birth, in 2009. An inductive
      qualitative framework analysis approach was used to identify and interpret themes
      explaining why pregnant women choose to drink or not. RESULTS: Women generally
      described drinking small amounts of alcohol during pregnancy as being a low risk
      activity and talked about the importance of alcohol to their social lives as a
      reason for continuing to drink or finding abstinence a burden; sensitisation to
      the judgements of others was not widespread. Women predominantly assessed the
      risk of their drinking in terms of the kinds of alcoholic beverages consumed
      rather than alcohol content. In reflecting on the advice they recalled receiving,
      women described their healthcare practitioners as being relaxed about the risks
      of alcohol consumption. CONCLUSIONS: The significance of alcohol to women's
      identity appeared to be an important reason for continued alcohol use during
      pregnancy among otherwise risk averse women. Anxiety about alcohol consumption
      during pregnancy was not widespread. However, obstetricians were an important
      mediator of this. Health messages that dispel the notion that wine is a "healthy"
      choice of alcoholic beverage, that provide women with strategies to help them
      avoid drinking, that advise the broader public not to pressure women to drink if
      they do not want to, and educate women about the effects of ethanol on maternal
      and fetal bodies, should be considered.

PMID- 25060556
TI  - Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate
      treatment are associated with losses of dimethylglycine and choline but not with
      increased losses of other osmolytes.
AB  - PURPOSE: Betaine deficiency is a probable cardiovascular risk factor and a cause
      of elevated homocysteine. Urinary betaine excretion is increased by fibrate
      treatment, and is also often elevated in diabetes. Does fibrate further increase
      betaine excretion in diabetes, and does it affect the plasma concentrations and
      excretions of related metabolites and of other osmolytes? METHODS: Samples from a
      previous study of type 2 diabetes were selected if participants were taking
      bezafibrate (n = 32). These samples were compared with participants matched for
      age and gender and not on a fibrate (comparator group, n = 64). Betaine, related
      metabolites, and osmolytes were measured in plasma and urine samples from these
      96 participants. RESULTS: Median urinary betaine excretion in those on
      bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself
      3.5-fold higher than the median reported for healthy populations. In the
      bezafibrate group, median dimethylglycine excretion was higher (9-fold, p <
      0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and
      glycerophosphorylcholine, were not significantly different between groups. Some
      participants excreted more betaine than usual dietary intakes. Several betaine
      fractional clearances were >100 %. Betaine excretion correlated with excretions
      of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the
      excretion of choline and N,N-dimethylglycine, but it was inconclusive whether
      these relationships were affected by bezafibrate therapy. CONCLUSIONS: Increased
      urinary betaine excretions in type 2 diabetes are further increased by fibrate
      treatment, sometimes to more than their dietary intake. Concurrent betaine
      supplementation may be beneficial.

PMID- 25060555
TI  - A signature of epithelial-mesenchymal plasticity and stromal activation in
      primary tumor modulates late recurrence in breast cancer independent of disease
      subtype.
AB  - INTRODUCTION: Despite improvements in adjuvant therapy, late systemic recurrences
      remain a lethal consequence of both early- and late-stage breast cancer. A
      delayed recurrence is thought to arise from a state of tumor dormancy, but the
      mechanisms that govern tumor dormancy remain poorly understood. METHODS: To
      address the features of breast tumors associated with late recurrence, but not
      confounded by variations in systemic treatment, we compiled breast tumor gene
      expression data from 4,767 patients and established a discovery cohort consisting
      of 743 lymph node-negative patients who did not receive systemic neoadjuvant or
      adjuvant therapy. We interrogated the gene expression profiles of the 743 tumors
      and identified gene expression patterns that were associated with early and late
      disease recurrence among these patients. We applied this classification to a
      subset of 46 patients for whom expression data from microdissected tumor
      epithelium and stroma was available, and identified a distinct gene signature in
      the stroma and also a corresponding tumor epithelium signature that predicted
      disease recurrence in the discovery cohort. This tumor epithelium signature was
      then validated as a predictor for late disease recurrence in the entire cohort of
      4,767 patients. RESULTS: We identified a novel 51-gene signature from
      microdissected tumor epithelium associated with late disease recurrence in breast
      cancer independent of the molecular disease subtype. This signature correlated
      with gene expression alterations in the adjacent tumor stroma and describes a
      process of epithelial to mesenchymal transition (EMT) and tumor-stroma
      interactions. CONCLUSIONS: Our findings suggest that an EMT-related gene
      signature in the tumor epithelium is related to both stromal activation and
      escape from disease dormancy in breast cancer. The presence of a late recurrence
      gene signature in the primary tumor also suggests that intrinsic features of this
      tumor regulate the transition of disseminated tumor cells into a dormant
      phenotype with the ability to outgrowth as recurrent disease.

PMID- 25060557
TI  - Central aortic pressure and pulsatility index in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We investigated the relationship between transcranial
      Doppler (TCD) pulsatility index (PI) and central aortic pressure by measurement
      of the aortic augmentation index (AIx). METHODS: We enrolled 148 consecutive
      patients with a diagnosis of acute ischemic stroke. Patients were eligible for
      the study if they experienced their first ischemic stroke within the preceding 7
      days and were 45 years of age or older. At Day 7 (+/-2) after stroke onset, TCD
      studies were performed and AIx was measured by applanation tonometry on the same
      days. RESULTS: The mean age was 66.3 (47-90) years and 37.8% were women. The mean
      middle cerebral artery (MCA) PI was significantly related with age (r =.361),
      hypertension (r = .184), peripheral systolic blood pressure (SBP; r = .211),
      peripheral pulse pressure (PP; r = .396), aortic SBP (r = .184), aortic DBP (r = 
      .181), and aortic PP (r = .371). The basilar artery (BA) PI was significantly
      related with age (r = .311), peripheral DBP (r = -.267), peripheral PP (r =
      .358), aortic DBP (r = -.266), and aortic PP (r = .347). CONCLUSIONS: TCD PI was
      significantly related with central aortic pressure, especially PP. The PI in the
      MCA and BA is closely associated with the pulsatile component of BP in the
      systemic circulation.

PMID- 25060558
TI  - Ask and you shall receive: desire and receipt of feedback via Facebook predicts
      disordered eating concerns.
AB  - OBJECTIVE: The current study examined whether certain types of Facebook content
      (i.e., status updates, comments) relate to eating concerns and attitudes. METHOD:
      We examined the effects of seeking and receiving negative feedback via Facebook
      on disordered eating concerns in a sample of 185 undergraduate students followed
      for approximately 4 weeks. RESULTS: Results indicated that individuals with a
      negative feedback seeking style who received a high number of comments on
      Facebook were more likely to report disordered eating attitudes four weeks later.
      Additionally, individuals who received extremely negative comments in response to
      their personally revealing status updates were more likely to report disordered
      eating concerns four weeks later. DISCUSSION: Results of the current study
      provide preliminary evidence that seeking and receiving negative feedback via
      social networking sites can increase risk for disordered eating attitudes, and
      suggest that reducing maladaptive social networking usage may be an important
      target for prevention and intervention efforts aimed at reducing disordered
      eating attitudes.

PMID- 25060559
TI  - Girdin, an actin-binding protein, is critical for migration, adhesion, and
      invasion of human glioblastoma cells.
AB  - Girdin, an actin-binding protein, possesses versatile functions in a multitude of
      cellular processes. Although several studies have shown that Girdin is involved
      in the cell DNA synthesis, actin cytoskeleton rearrangement, and cell motility,
      the molecular mechanisms of Girdin in tumor development and progression remain
      elusive. In this study, through over-expression and siRNA experiments, we found
      that Girdin increased migration of LN229 human glioblastoma cells. On the other
      hand, reducing Girdin impaired F-actin polymerization, which is essential for
      cell morphogenesis and motility. Matrix metalloproteinase 2, critical in human
      glioma migration and invasion, was down-regulated upon Girdin reduction and led
      to decreased invasion in vitro and in vivo. In addition, silencing Girdin
      expression impaired the phosphorylation of two important adhesion molecules,
      integrin beta1 and focal adhesion kinase, resulting in cell adhesion defects. Our
      immunohistochemical study on human gliomas tissue sections indicated that Girdin
      expression was positively related with glioma malignancy, supporting the in vitro
      and in vivo results from cell lines. Collectively, our findings suggest a
      critical role for Girdin in glioma infiltration. We show that reduction of
      Girdin, an actin-binding protein, leads to impaired F-actin polymerization and
      down-regulated expression of matrix metallopeptidase protein 2 (MMP-2),
      phosphorylated integrin beta1, and phosphorylated focal adhesion kinase (FAK),
      which resulted in decreased migration, adhesion, and invasion of glioblastoma
      cells. Girdin was positively correlated with glioma malignancy and negatively
      associated with clinical prognosis, suggesting Girdin as a critical regulator in
      glioma infiltration. 

PMID- 25060560
TI  - Results of the Oxford Phase 3 mobile bearing medial unicompartmental knee
      arthroplasty from an independent center: 467 knees at a mean 6-year follow-up:
      analysis of predictors of failure.
AB  - A retrospective review of 467 Oxford UKAs was performed in 387 patients. Thirty
      eight knees (8.1%) were revised to TKA at a mean of 49 months, most commonly for
      lateral compartment OA (47%). The 5-year cumulative survival using revision to
      TKA was 98.5%. Revisions required short stems in 26% and augments in 21% of
      cases. The mobile bearing dislocation rate was 0.64%. Correction of >=3-5 degrees
      from the preoperative alignment in a valgus direction was predictive of revision
      to TKA (P<.0001). Multivariate analysis revealed female gender (P=.002) also was
      associated with an increased risk of revision. Careful attention to the degree of
      mechanical axis correction with an overall maintained varus alignment may reduce
      revision rates for mobile bearing UKA.

PMID- 25060561
TI  - A novel methodological approach for measuring symptomatic change following total
      joint arthroplasty.
AB  - The OHS/OKS are PROMs for assessing symptomatic pain and function following TJA.
      However, actual change in pre-operative/post-operative scores cannot distinguish
      patients of varying baseline symptom severity. The percentage of potential change
      (PoPC) is a simple method that accounts for this, expressing the actual change
      attained, as a percentage of the potential change possible. Measures are
      described using OHS/OKS at baseline and 6-months (1784 - TKA, 1523 - THA) from
      the Elective Orthopaedic Centre. Each method identified different proportions of
      patients as satisfied and importantly, the measures identified different
      patients. PoPC overcomes floor and ceiling effects and standardises measures to
      an easy to interpret -100 to +100 scale. In addition to actual change, we
      recommend using PoPC to assess the overall outcome of patients. 

PMID- 25060562
TI  - Correlation of corrosion and biomechanics in the retrieval of a single modular
      neck total hip arthroplasty design: modular neck total hip arthroplasty system.
AB  - Increased modularity of total hip arthroplasty components has occurred, with
      theoretical advantages and disadvantages. Recent literature indicates the
      potential for elevated revision rates of modular neck systems and the potential
      for local pseudotumor and metallosis formation at the modular neck/stem site.
      Retrieval analysis of one modular neck implant design including SEM (SCANNING
      ELECTRON MICROSCOPY) assessment was done and correlated with FEA (finite element
      analysis) as well as clinical features of patient demographics, implant and
      laboratory analysis. Correlation of the consistent corrosion locations to FEA
      indicates that the material and design features of this system may result in a
      biomechanical reason for failure. The stem aspect of the modular neck/stem
      junction may be at particular risk.

PMID- 25060563
TI  - Chitosan coating incorporated with the lactoperoxidase system: an active edible
      coating for fish preservation.
AB  - BACKGROUND: As a result of consumers' concerns about chemicals there is a
      particular interest in the food industry to use natural bio-preservatives such as
      antimicrobial enzymes for antimicrobial packaging. Based on the antimicrobial
      activity of the lactoperoxidase system (LPOS), the present study evaluated the
      coating effect of LPOS incorporated into chitosan solution (CH) on the quality
      and shelf life extension of rainbow trout during refrigerated storage (4 +/- 1 
      degrees C), for a period of 16 days. RESULTS: The results indicated that samples
      of the CH+LPOS group had significantly lower numbers of Shewanella putrefaciens,
      Pseudomonas fluorescens, and psychrotrophic and mesophilic bacteria than did the
      CH and control group during the entire storage period. Total volatile basic
      nitrogen (TVB-N) levels for the CH+LPOS samples (22.07 mg 100 g(-1)) did not
      exceed the limit of consumption (30-35 mg N 100 g(-1)), while the CH (31.03 mg
      100 g(-1) ) and control groups (37.78 mg 100 g(-1) ) reached this level at days
      12 and 16, respectively. Thiobarbituric acid values of the CH and CH+LPOS
      samples, ranged between 0.49 and 0.51 on day 0 and 4.59-4.66 mg kg(-1) on day 16,
      were significantly lower (P < 0.05) than the corresponding values of the control
      samples (0.47 on day 0 to 4.78 mg kg(-1) on day 16 of storage) during the chilled
      storage period. CONCLUSION: The coating treatments (CH and CH+LPOS) extended the
      shelf life of trout fillets by at least 4 days as compared to the control
      samples, so that they showed moderate to high acceptability in all investigated
      sensory attributes even on the 16th day of storage.

PMID- 25060564
TI  - Maternal vegetarianism and neurodevelopment of children enrolled in The Danish
      National Birth Cohort.

PMID- 25060565
TI  - A direct synthesis of selenophenes by Cu-catalyzed one-pot addition of a selenium
      moiety to (E,E)-1,3-dienyl bromides and subsequent nucleophilic cyclization.
AB  - An efficient protocol for the synthesis of selenophenes and selanyl selenophenes
      has been achieved by a simple one-pot reaction of 1,3-dienyl bromides and 1,3
      dienyl-gem-dibromides respectively with KSeCN catalyzed by CuO nanoparticles.
      Several aryl, alkenyl, heteroaryl, and alkyl substituted selenophenes were
      obtained with a broad array of functional group tolerance. This is found to be a
      general methodology for chalcogenophenes being effective for the synthesis of
      thiophenes too. 

PMID- 25060566
TI  - SMAD4 and TS expression might predict the risk of recurrence after resection of
      colorectal liver metastases.
AB  - PURPOSE: Colorectal liver metastases (CLM) have significant molecular
      heterogeneity, which contributes to the risk of recurrence following surgery.
      Most of the traditional scores intended to predict recurrence is based on
      clinicopathological variables and it is unclear whether incorporating molecular
      biomarkers might improve our assessment of the risk of recurrence. Our aim was to
      determine if molecular biomarkers might be associated with the risk of recurrence
      after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed
      with colorectal cancer (CRC) with resected liver metastases were included. The
      role of several clinicopathological variables to predict patient's outcome after
      resection of liver metastases was analyzed. Eighteen genes related to CRC
      pathogenesis were also included in the analyses. Univariate and multivariate
      stepwise Cox regression analyses were performed to identify factors associated
      with recurrence and the risk of death. RESULTS: Eight prognostic factors for
      progression-free survival and nine factors for overall survival were identified
      in the univariate analyses. After adjusting for other risk factors, only the
      expression of two molecular factors was associated with the risk of recurrence:
      TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695).
      None of the variables was significantly associated with the risk of death in the
      multivariate analyses. CONCLUSIONS: The prognostic significance of most
      traditional clinicopathological variables might be insufficient to define
      patients at risk for recurrence after liver metastases resection. Molecular
      biomarkers might improve the identification of patients with higher risk of
      recurrence.

PMID- 25060567
TI  - The intra-tumor heterogeneity of cell signaling factors in breast cancer: p4E-BP1
      and peIF4E are diffusely expressed and are real potential targets.
AB  - Breast cancers and most malignant tumors are composed of heterogeneous tumor
      cells both at genetic and morphological levels; intra-tumor heterogeneity can be
      one underlying cause of therapeutic resistance. Classical studies have focused on
      analyses of the relationship between primary tumors and metastatic dissemination,
      and on subclone evolution. However, it should be noted that tumor heterogeneity
      at the level of protein expression (proteomics) has not been yet studied in
      depth. The differences in protein expression also can play an important role in
      elucidating the relationship between intra-tumor heterogeneity and resistance to
      systemic therapy. In fact, in human tumors there is not always a homogeneous
      expression of many of the crucial factors involved in cell signaling, such as
      pMAPK, pAKt, pMTOR, even with constitutive oncogenic alterations upstream, such
      as HER2, PI3 K. Conversely, two of these factors, peIF4E and p4E-BP1, which are
      downstream, and control protein translation, show a diffuse and strong protein
      expression. In summary, most of cell signaling factors show a heterogeneous
      expression, regardless of oncogenic alterations. Tissue heterogeneity could be
      driven by local factors, including hypoxia. The fact that the phosphorylation of
      crucial proteins such as 4E-BP1 and eIF4E is observed homogeneously throughout
      most tumors and are druggable opens the chance to get real potential targets in
      cancer therapy.

PMID- 25060568
TI  - Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity
      and apoptosis in DU-145 human prostate cancer cells by modulating PI3K-AKT
      pathway.
AB  - BACKGROUND: The treatment of castrate-resistant prostate cancer (CRPC) still
      remains as an important challenge of daily oncology practice. Docetaxel
      significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one
      of the flavonoid compounds isolated from Nigealla sativa, has been shown to
      possess cytotoxic activity against a variety of cancer cell lines. MATERIALS AND
      METHODS: The aim of the study was to investigate the possible synergistic
      cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145
      hormone- and drug-refractory prostate cancer cells and their effects on PI3K and
      ERK signaling pathways. RESULTS: We observed that the combination of docetaxel
      and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared
      to any single agent alone, in a dose-dependent manner. It was found that
      viability of the combination treated cells was not significantly changed in the
      presence of LY294002 as compared to inhibitor treated cells. However, in the
      presence of FR180204, viability of combination treated cells was significantly
      decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect
      of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt
      signaling pathway in DU-145 cells. CONCLUSION: Therefore, this combination
      strategy may be an alternative approach for the challenging era of daily
      oncologic practice. Also, the combination of docetaxel and TQ might allow a
      reduction in docetaxel doses and diminish adverse effects of docetaxel while
      maintaining the therapeutic effect in patients with CRPC.

PMID- 25060569
TI  - Complementary compressive imaging for the telescopic system.
AB  - Conventional single-pixel cameras recover images only from the data recorded in
      one arm of the digital micromirror device, with the light reflected to the other
      direction not to be collected. Actually, the sampling in these two reflection
      orientations is correlated with each other, in view of which we propose a
      sampling concept of complementary compressive imaging, for the first time to our
      knowledge. We use this method in a telescopic system and acquire images of a
      target at about 2.0 km range with 20 cm resolution, with the variance of the
      noise decreasing by half. The influence of the sampling rate and the integration
      time of photomultiplier tubes on the image quality is also investigated
      experimentally. It is evident that this technique has advantages of large field
      of view over a long distance, high-resolution, high imaging speed, high-quality
      imaging capabilities, and needs fewer measurements in total than any single-arm
      sampling, thus can be used to improve the performance of all compressive imaging
      schemes and opens up possibilities for new applications in the remote-sensing
      area.

PMID- 25060570
TI  - Spread of chikungunya from the Caribbean to mainland Central and South America: a
      greater risk of spillover in Europe?

PMID- 25060571
TI  - Cases of chikungunya virus infection in travellers returning to Spain from Haiti
      or Dominican Republic, April-June 2014.
AB  - Ten cases of chikungunya were diagnosed in Spanish travellers returning from
      Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between
      April and June 2014. These cases remind clinicians to consider chikungunya in
      European travellers presenting with febrile illness and arthralgia, who are
      returning from the Caribbean region and Central America, particularly from Haiti
      and the Dominican Republic. The presence of Aedes albopictus together with
      viraemic patients could potentially lead to autochthonous transmission of
      chikungunya virus in southern Europe.

PMID- 25060572
TI  - Large number of imported chikungunya cases in mainland France, 2014: a challenge
      for surveillance and response.
AB  - During the summer of 2014, all the pre-requisites for autochthonous transmission
      of chikungunya virus are present in southern France: a competent vector, Aedes
      albopictus, and a large number of travellers returning from the French Caribbean
      islands where an outbreak is occurring. We describe the system implemented for
      the surveillance of chikungunya and dengue in mainland France. From 2 May to 4
      July 2014, there were 126 laboratory-confirmed imported chikungunya cases in
      mainland France.

PMID- 25060573
TI  - Local and regional spread of chikungunya fever in the Americas.
AB  - Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is
      currently affecting several areas in the Caribbean. The vector is found in the
      Americas from southern Florida to Brazil, and the Caribbean is a highly connected
      region in terms of population movements. There is therefore a significant risk
      for the epidemic to quickly expand to a wide area in the Americas. Here, we
      describe the spread of CHIKV in the first three areas to report cases and between
      areas in the region. Local transmission of CHIKV in the Caribbean is very
      effective, the mean number of cases generated by a human case ranging from two to
      four. There is a strong spatial signature in the regional epidemic, with the risk
      of transmission between areas estimated to be inversely proportional to the
      distance rather than driven by air transportation. So far, this simple distance
      based model has successfully predicted observed patterns of spread. The spatial
      structure allows ranking areas according to their risk of invasion. This
      characterisation may help national and international agencies to optimise
      resource allocation for monitoring and control and encourage areas with elevated
      risks to act.

PMID- 25060575
TI  - ANGPTL4 regulates the metastatic potential of oral squamous cell carcinoma.
AB  - Lymph node metastasis is a major factor for poor prognosis in oral squamous cell
      carcinoma (OSCC). However, the molecular mechanisms of lymph node metastasis are
      unclear. We determined that angiopoietin-like protein 4 (ANGPTL4) mRNA and
      protein expression were increased in OSCC cells established from the primary site
      in metastatic cases. In addition, ANGPTL4 expression in biopsy specimens was
      correlated with the presence of lymph node metastasis. Therefore, our initial
      findings suggest that OSCC cells expressing ANGPTL4 may possess metastatic
      ability. Furthermore, cell culture supernatants from OSCC cells that metastasized
      to the lymph node contain ANGPTL4 and promote invasive ability. These findings
      suggest that secreted ANGPTL4 may affect the invasive ability of OSCC. Moreover,
      the rates of positive ANGPTL4 expression at the primary site were significantly
      higher in the lymph node metastasis group. These results demonstrate that ANGPTL4
      contributes to OSCC metastasis by stimulating cell invasion. Therefore, ANGPTL4
      is a potential therapeutic target for preventing cancer metastasis. 

PMID- 25060576
TI  - Individual differences in learning speed, performance accuracy and exploratory
      behaviour in black-capped chickadees.
AB  - Cognitive processes are important to animals because they not only influence how
      animals acquire, store and recall information, but also may underpin behaviours
      such as deciding where to look for food, build a nest, or with whom to mate.
      Several recent studies have begun to examine the potential interaction between
      variation in cognition and variation in personality traits. One hypothesis
      proposed that there is a speed-accuracy trade-off in cognition ability that
      aligns with a fast-slow behaviour type. Here, we explicitly examined this
      hypothesis by testing wild-caught black-capped chickadees in a series of
      cognitive tasks that assessed both learning speed (the number of trials taken to
      learn) and accuracy (post-acquisition performance when tested with un-trained
      exemplars). Chickadees' exploration scores were measured in a novel environment
      task. We found that slow-exploring chickadees demonstrated higher accuracy during
      the test phase, but did not learn the initial task in fewer trials compared to
      fast-exploring chickadees, providing partial support for the proposed link
      between cognition and personality. We report positive correlations in learning
      speed between different phases within cognitive tasks, but not between the three
      cognitive tasks suggesting independence in underlying cognitive processing. We
      discuss different rule-based strategies that may contribute to differential
      performance accuracy in cognitive tasks and provide suggestions for future
      experimentation to examine mechanisms underlying the relationship between
      cognition and personality. 

PMID- 25060577
TI  - Mice use start point orientation to solve spatial problems in a water T-maze.
AB  - Behavioral work has demonstrated that rats solve many spatial problems using a
      conditional strategy based on orientation at the start point. The present study
      assessed whether mice use a similar strategy and whether the strategy would be
      affected by the poorer directional sensitivity of mice. In Experiment 1, mice
      were trained on a response, a direction or one of two place problems to locate a
      hidden platform in a water T-maze located in two positions. In the response task,
      mice made a right (or left) turn from two different start points located 180
      degrees  apart. In the direction task, the maze was shifted (to the left or
      right) and the start points rotated by 180 degrees  across trials, but the
      platform was in a constant direction relative to room cues. In the translation
      place task, the mice were trained to locate the platform in a fixed location
      relative to extra-maze cues when the maze was shifted across trials, but the
      orientation of the start arm did not change. In the rotation place task, the mice
      were trained to locate the platform in a fixed location when the maze was shifted
      and the start points rotated by 90 degrees  across trials. As previously reported
      with rats, mice had difficulty solving the translation place problem compared
      with the other three problems. Unlike rats, mice learned the direction problem in
      significantly fewer trials than the rotation problem. This difference between
      acquisition of the direction and rotation problems was replicated in Experiment
      2. The difficulty mice have in discriminating start point orientations that are
      90 degrees  apart as opposed to 180 degrees  apart can be attributed to the
      broader firing ranges of HD cells in mice compared with rats. 

PMID- 25060578
TI  - T cell recognition: A hidden heavy metal.

PMID- 25060574
TI  - Nutritional psychiatry research: an emerging discipline and its intersection with
      global urbanization, environmental challenges and the evolutionary mismatch.
AB  - In 21st-century public health, rapid urbanization and mental health disorders are
      a growing global concern. The relationship between diet, brain function and the
      risk of mental disorders has been the subject of intense research in recent
      years. In this review, we examine some of the potential socioeconomic and
      environmental challenges detracting from the traditional dietary patterns that
      might otherwise support positive mental health. In the context of urban
      expansion, climate change, cultural and technological changes and the global
      industrialization and ultraprocessing of food, findings related to nutrition and
      mental health are connected to some of the most pressing issues of our time. The
      research is also of relevance to matters of biophysiological anthropology. We
      explore some aspects of a potential evolutionary mismatch between our ancestral
      past (Paleolithic, Neolithic) and the contemporary nutritional environment.
      Changes related to dietary acid load, advanced glycation end products and
      microbiota (via dietary choices and cooking practices) may be of relevance to
      depression, anxiety and other mental disorders. In particular, the results of
      emerging studies demonstrate the importance of prenatal and early childhood
      dietary practices within the developmental origins of health and disease concept.
      There is still much work to be done before these population studies and their
      mirrored advances in bench research can provide translation to clinical medicine
      and public health policy. However, the clear message is that in the midst of a
      looming global epidemic, we ignore nutrition at our peril. 

PMID- 25060579
TI  - Developmental gene networks: a triathlon on the course to T cell identity.
AB  - Cells acquire their ultimate identities by activating combinations of
      transcription factors that initiate and sustain expression of the appropriate
      cell type-specific genes. T cell development depends on the progression of
      progenitor cells through three major phases, each of which is associated with
      distinct transcription factor ensembles that control the recruitment of these
      cells to the thymus, their proliferation, lineage commitment and responsiveness
      to T cell receptor signals, all before the allocation of cells to particular
      effector programmes. All three phases are essential for proper T cell
      development, as are the mechanisms that determine the boundaries between each
      phase. Cells that fail to shut off one set of regulators before the next gene
      network phase is activated are predisposed to leukaemic transformation. 

PMID- 25060580
TI  - Assembly and localization of Toll-like receptor signalling complexes.
AB  - Signal transduction by the Toll-like receptors (TLRs) is central to host defence
      against many pathogenic microorganisms and also underlies a large burden of human
      disease. Thus, the mechanisms and regulation of signalling by TLRs are of
      considerable interest. In this Review, we discuss the molecular basis for the
      recognition of pathogen-associated molecular patterns, the nature of the protein
      complexes that mediate signalling, and the way in which signals are regulated and
      integrated at the level of allosteric assembly, post-translational modification
      and subcellular trafficking of the components of the signalling complexes. These
      fundamental molecular mechanisms determine whether the signalling output leads to
      a protective immune response or to serious pathologies such as sepsis. A detailed
      understanding of these processes at the molecular level provides a rational
      framework for the development of new drugs that can specifically target
      pathological rather than protective signalling in inflammatory and autoimmune
      disease. 

PMID- 25060581
TI  - Immune modulation by butyrophilins.
AB  - The B7 family of co-stimulatory molecules has an important role in driving the
      activation and inhibition of immune cells. Evolving data have shown that a
      related family of molecules - the butyrophilins - have similar immunomodulatory
      functions to B7 family members and may represent a novel subset of co-stimulatory
      molecules. These studies have taken the field by surprise, as the butyrophilins
      were previously thought to only be important in lactation and milk production. In
      this Review, we describe the expression patterns of the various members of the
      butyrophilin family and explore their immunomodulatory functions. In particular,
      we emphasize the contribution of butyrophilins to immune homeostasis and discuss
      the potential of targeting these molecules for therapeutic purposes. 

PMID- 25060582
TI  - First-line combination chemotherapy with cisplatin, etoposide and ifosfamide for
      the treatment of disseminated germ cell cancer: re-evaluation in the granulocyte
      colony-stimulating factor era.
AB  - BACKGROUND: This study re-evaluated the efficacy and tolerability of cisplatin,
      etoposide, and ifosfamide (VIP) combination chemotherapy as an alternative first
      line regimen for patients with disseminated germ cell cancer (GCC) in this
      granulocyte colony-stimulating factor (G-CSF) era. METHODS: The medical records
      of 91 consecutive patients with previously untreated disseminated GCC who
      received first-line VIP between 1995 and 2011 were retrospectively reviewed.
      RESULTS: The 5-year overall survival rates for patients with good (n = 49),
      intermediate (n = 22) and poor (n = 20) prognoses according to the International
      Germ Cell Cancer Collaborative Group classification were 100, 79 and 83%,
      respectively. G-CSF was given to all patients, and no treatment-related deaths
      due to myelosuppression occurred. CONCLUSION: The present study is the first to
      examine the therapeutic outcomes and safety profile of first-line VIP after
      routine G-CSF use. VIP might be an alternative first-line regimen for patients
      with disseminated GCC in this G-CSF era.

PMID- 25060583
TI  - A magnetic resonance imaging study on the articulatory and acoustic speech
      parameters of Malay vowels.
AB  - The phonetic properties of six Malay vowels are investigated using magnetic
      resonance imaging (MRI) to visualize the vocal tract in order to obtain dynamic
      articulatory parameters during speech production. To resolve image blurring due
      to the tongue movement during the scanning process, a method based on active
      contour extraction is used to track tongue contours. The proposed method
      efficiently tracks tongue contours despite the partial blurring of MRI images.
      Consequently, the articulatory parameters that are effectively measured as tongue
      movement is observed, and the specific shape of the tongue and its position for
      all six uttered Malay vowels are determined.Speech rehabilitation procedure
      demands some kind of visual perceivable prototype of speech articulation. To
      investigate the validity of the measured articulatory parameters based on
      acoustic theory of speech production, an acoustic analysis based on the uttered
      vowels by subjects has been performed. As the acoustic speech and articulatory
      parameters of uttered speech were examined, a correlation between formant
      frequencies and articulatory parameters was observed. The experiments reported a
      positive correlation between the constriction location of the tongue body and the
      first formant frequency, as well as a negative correlation between the
      constriction location of the tongue tip and the second formant frequency. The
      results demonstrate that the proposed method is an effective tool for the dynamic
      study of speech production. 

PMID- 25060584
TI  - Advanced retorting, microwave assisted thermal sterilization (MATS), and pressure
      assisted thermal sterilization (PATS) to process meat products.
AB  - Conventional thermal processes have been very reliable in offering safe
      sterilized meat products, but some of those products are of questionable overall
      quality. Flavor, aroma, and texture, among other attributes, are significantly
      affected during such processes. To improve those quality attributes, alternative
      approaches to sterilizing meat and meat products have been explored in the last
      few years. Most of the new strategies for sterilizing meat products rely on using
      thermal approaches, but in a more efficient way than in conventional methods.
      Some of these emerging technologies have proven to be reliable and have been
      formally approved by regulatory agencies such as the FDA. Additional work needs
      to be done in order for these technologies to be fully adopted by the food
      industry and to optimize their use. Some of these emerging technologies for
      sterilizing meat include pressure assisted thermal sterilization (PATS),
      microwaves, and advanced retorting. This review deals with fundamental and
      applied aspects of these new and very promising approaches to sterilization of
      meat products. 

PMID- 25060585
TI  - Science and animal welfare in France and European Union: Rules, constraints,
      achievements.
AB  - The welfare of food-producing animals is a focus of public debate in Europe.
      Political institutions, have introduced regulations based on scientific data.
      Meanwhile, the practices of producers and transformers were modified.
      Implementation of care practices is added to the goal of sustainable basic health
      of animals. Nevertheless urban consumers still look for the "naturalness" of
      living animals. A brief historical perspective introduces the building process of
      European regulations. A short list of Directories and Recommendations provides a
      clue on the complexity of resulting construct. Now, this complexity is calling
      for simplification of rules while practices should be compatible with
      professional constraints. Few selected examples are brought to illustrate how the
      concepts initially studied by scientists (welfare, pain, stress,
      "consciousness"/awareness) were integrated in regulations and implemented by
      producers and meat industry in order to simultaneously maintain the requirements
      for high quality and security standards. At the same time, free trade market
      constraints introduced new distortions, in particular those linked to the world
      demand for proteins. Indeed, the controversy about animal welfare, initially
      brought on ethical grounds, became a case for ongoing adjustements of EU policy,
      requesting to combine scientific knowledge on animals, consequent evolution in
      the representation of animals by urban consumers with the challenge of adaptation
      and implemention of regulations. 

PMID- 25060586
TI  - Meat consumption: trends and quality matters.
AB  - This paper uses quality theory to identify opportunities for the meat sector that
      are consistent with trends in meat consumption. Meat consumption has increased
      and is likely to continue into the future. Growth is largely driven by white
      meats, with poultry in particular of increasing importance globally. The
      influence of factors such as income and price is likely decline over time so that
      other factors, such as quality, will become more important. Quality is complex
      and consumers' quality expectations may not align with experienced quality due to
      misconception of certain intrinsic cues. Establishing relevant and effective
      cues, based on extrinsic and credence attributes, could offer advantage on the
      marketplace. The use of extrinsic cues can help convey quality characteristics
      for eating quality, but also for more abstract attributes that reflect individual
      consumer concerns e.g. health/nutrition, and collective concerns, e.g.
      sustainability. However, attributes are not of equal value to all consumers. Thus
      consumer segmentation and production differentiation is needed. 

PMID- 25060587
TI  - Ventilation/perfusion ratios measured by multiple inert gas elimination during
      experimental cardiopulmonary resuscitation.
AB  - BACKGROUND: During cardiopulmonary resuscitation (CPR) the ventilation/perfusion
      distribution (VA /Q) within the lung is difficult to assess. This experimental
      study examines the capability of multiple inert gas elimination (MIGET) to
      determine VA /Q under CPR conditions in a pig model. METHODS: Twenty-one
      anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0,
      0.7 or 0.21). VA/ Q by micropore membrane inlet mass spectrometry-derived MIGET
      was determined at baseline and during CPR following induction of ventricular
      fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical
      impedance tomography and return of spontaneous circulation were assessed.
      Intergroup differences were analysed by non-parametric testing. RESULTS: MIGET
      measurements were feasible in all animals with an excellent correlation of
      measured and predicted arterial oxygen partial pressure (R(2)  = 0.96, n = 21 for
      baseline; R(2)  = 0.82, n = 21 for CPR). CPR induces a significant shift from
      normal VA /Q ratios to the high VA /Q range. Electrical impedance tomography
      indicates a dorsal to ventral shift of the ventilation distribution. Diverging
      pulmonary shunt fractions induced by the three inspired oxygen levels
      considerably increased during CPR and were traceable by MIGET, while 100% oxygen
      most negatively influenced the VA /Q. Return of spontaneous circulation were
      achieved in 52% of the animals. CONCLUSIONS: VA /Q assessment by MIGET is
      feasible during CPR and provides a novel tool for experimental purposes. Changes
      in VA /Q caused by different oxygen fractions are traceable during CPR. Beyond
      pulmonary perfusion deficits, these data imply an influence of the inspired
      oxygen level on VA /Q. Higher oxygen levels significantly increase shunt
      fractions and impair the normal VA /Q ratio.

PMID- 25060588
TI  - MYC-associated and double-hit lymphomas: a review of pathobiology, prognosis, and
      therapeutic approaches.
AB  - Aberrant expression of the v-myc avian myelocytomatosis viral oncogene homolog
      (MYC) proto-oncogene has known transformative potential in healthy human cells.
      Chromosomal MYC rearrangements and consequent MYC overexpression is the defining
      lesion in Burkitt lymphoma (BL), conferring a highly proliferative state.
      However, abnormalities of MYC are increasingly appreciated in non-BL histologies,
      including diffuse large B-cell lymphoma (DLBCL) and B-cell lymphomas intermediate
      between BL and DLBCL, with a particularly aggressive clinical phenotype. Although
      there are conflicting data regarding prognostic implications of isolated MYC
      aberrancy in these non-BLs, the co-occurrence of MYC rearrangements and either
      the antiapoptotic gene B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) or
      the transcriptional repressor BCL6 leads to an entity termed double-hit B-cell
      lymphoma (DHL) (or triple-hit if all 3 abnormalities are observed) with a
      particularly poor prognosis and no established treatment paradigms. Notably, a
      distinct pattern of gene expression profiling has been noted when MYC is
      overexpressed in BL compared with other lymphomas, supporting the notion that,
      although MYC promotes target gene transcription, the target genes vary by disease
      subtype. The frequency of MYC activity depends on the method of detection and
      ranges from 5% to 10% using fluorescence in situ hybridization but up to 30% of
      DLBCL using immunohistochemistry. Standard therapies developed for DLBCL are less
      effective when the disease is driven by MYC, leading to lower response rates and
      response durations. An important clinical challenge is to pre-emptively identify
      MYC-associated lymphomas and to subsequently develop trials specifically for this
      group of patients. However, the design of such studies is complicated by variable
      definitions of MYC-associated lymphoid malignancies and the lack of effective
      therapies to date. The objective if the current review was to evaluate the
      implications of MYC aberrancy with respect to the B-cell lymphoma double-hit and
      triple-hit phenotypes and to consider the available data for clinical and
      practical management.

PMID- 25060589
TI  - Concurrent therapy with taxane versus non-taxane containing regimens in locally
      advanced squamous cell carcinomas of the head and neck (SCCHN): a systematic
      review.
AB  - BACKGROUND: Platinum compounds remain the most widely utilized systemic agents in
      combination with radiation for treating SCCHN in the concurrent setting. Despite
      recent interest in using taxanes in this setting, there is a lack of randomized
      clinical trials to support this approach. We conducted a systematic review of
      published clinical trials of taxane-containing versus standard non-taxane-based
      regimens used in definitive treatment of SCCHN. METHODS: Trials published between
      1994 and 2012 were identified by an electronic search of public databases
      (MEDLINE, EMBASE, Cochrane library). All prospective studies were independently
      identified by two authors for inclusion. Studies were excluded if induction
      therapy was part of the regimen or if targeted agents were used. Trials using
      cisplatin- or carboplatin-based regimens and paclitaxel or docetaxel were
      included. Demographic data, treatment response, locoregional failure free rate
      (LFFR), progression-free and overall survival (PFS, OS) and toxicities were
      extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0).
      Outcome data were pooled and reported as weighted response rate (RR), PFS and OS.
      RESULTS: A total of 790 studies were retrieved and 42 studies with 3120 patients
      were included: 804 patients were treated with taxanes (80% males, median age
      57years) and 2316 with non-taxanes (86% males, median age 56years). Progression
      free survival was not different between the two groups. Weighted median survival
      was compared from those studies that reported these data; taxanes=36.7months
      (N=197) versus non-taxanes=25months (N=503), P<0.001. Toxicity (grade 3 and
      above) was higher in non-taxane containing trials. CONCLUSIONS: The improved
      overall survival observed supports the choice of taxane-based regimens in the
      concurrent setting but may also reflect the predominance of single arm multi
      agent phase II trials in the taxane arm. Our findings urge the need for better
      standardization of taxane-based regimens.

PMID- 25060590
TI  - Evaluation of the WATCHMAN left atrial appendage closure device.
AB  - Left atrial appendage device occlusion for the preventions of systemic
      thromboembolism and stroke represents a major breakthrough in the field of
      cardiovascular disease. The wide prevalence of atrial fibrillation with
      devastating consequences of thromboembolic stroke as a result of thrombus arising
      from the left atrial appendage has led to the development of transcatheter and
      surgical based occlusion devices. Though this device is yet to be formally
      approved for a clinical indication in the USA, the WATCHMAN appendage occlusion
      device remains the most rigorously examined and studied of all transcatheter
      based devices in this space. This review will focus on the needs assessment in
      this space, the technology of the current WATCHMAN device, trials and studies
      looking at safety and efficacy, specific patient populations who might benefit as
      well as future perspectives. 

PMID- 25060591
TI  - [Early detection, prevention and management of renal failure in liver
      transplantation].
AB  - Renal failure is a frequent complication in liver transplant recipients and is
      associated with increased morbidity and mortality. A variety of risk factors for
      the development of renal failure in the pre- and post-transplantation periods
      have been described, as well as at the time of surgery. To reduce the negative
      impact of renal failure in this population, an active approach is required for
      the identification of those patients with risk factors, the implementation of
      preventive strategies, and the early detection of progressive deterioration of
      renal function. Based on published evidence and on clinical experience, this
      document presents a series of recommendations on monitoring RF in LT recipients,
      as well as on the prevention and management of acute and chronic renal failure
      after LT and referral of these patients to the nephrologist. In addition, this
      document also provides an update of the various immunosuppressive regimens tested
      in this population for the prevention and control of post-transplantation
      deterioration of renal function. 

PMID- 25060592
TI  - Revisionist or simply wrong? A rejoinder.

PMID- 25060593
TI  - Disease-specific death and metastasis do not occur in patients with Gleason score
      <=6 at radical prostatectomy.
AB  - OBJECTIVES: To assess the metastasis-free survival (MFS) and disease-specific
      survival (DSS) in men with Gleason score <=6 prostate cancer at radical
      prostatectomy (RP). PATIENTS AND METHODS: We included 1101 consecutive RP
      patients operated between March 1985 to July 2013 at a single institution. The
      outcome variables were MFS and DSS. The postoperative survival was estimated by
      the Kaplan-Meier method. RESULTS: The Gleason score distribution of the study
      population (1101 patients) was Gleason score <=6 (449, 41%), Gleason score 3 + 4
      = 7 (436, 40%), Gleason score 4 + 3 = 7 (99, 9%) and Gleason score 8-10 (117,
      11%). The median (interquartile range) postoperative follow-up was 100 (48-150)
      months. During follow-up 197 men (18%) died, of whom 42 (3.8%) died from prostate
      cancer-related causes. In all, 19/1101 patients (1.7%) had documented lymph node
      metastasis at the time of RP: none with Gleason score <=6, seven with Gleason
      score 3 + 4 = 7 (1.6%), six with Gleason score 4 + 3 = 7 (6.1%) and six with
      Gleason score 8-10 (5.1%). Distant metastasis occurred in 56/1101 patients
      (5.1%): none with Gleason score <=6, 23 with Gleason score 3 + 4 = 7 (5.3%), 17
      with Gleason score 4 + 3 = 7 (17%) and 16 with Gleason score 8-10 (14%). Disease
      specific death, stratified per Gleason-score group was: none in <=6, 16 (3.7%) in
      3 + 4 = 7, 16 (16%) in 4 + 3 = 7 and 10 (8.5%) in 8-10 group. CONCLUSION: No
      metastasis or disease-specific death were seen in men with Gleason score <=6
      prostate cancer at RP, showing the negligible potential to metastasise in this
      large subgroup of patients with prostate cancer.

PMID- 25060595
TI  - Maternal life course socio-economic position and offspring body composition at
      birth in a multi-ethnic population.
AB  - BACKGROUND: Size and body composition at birth may affect long-term health. Mean
      birthweight and body composition differ between ethnic groups living in Europe.
      We wanted to explore if this relates to differences in socio-economic conditions
      in country of origin and over the maternal life course. METHODS: This is a
      population-based cohort study of healthy pregnant women living in Oslo, Norway.
      Data on maternal early life and present socio-economic position (SEP) were
      collected in early gestation, and SEP scores were extracted through two separate
      principal components analyses. The associations between maternal present SEP and
      four different offspring anthropometric measures at birth were assessed
      separately, stratified by maternal early life SEP (dichotomised score) and Human
      Development Index (HDI, a country-level socio-economic indicator) in the country
      of origin [high HDI (Reference), n = 287 and low HDI, n = 250]. RESULTS: A strong
      positive association between maternal present SEP and offspring birthweight was
      observed if maternal early life SEP was high, but not if maternal early life SEP
      was low (P < 0.001 for the interaction term). This interactional effect was
      observed in both HDI groups. Maternal life course SEP affected offspring
      birthweight mainly through an effect on length and sum of skin folds. Offspring
      of mothers with origin from low HDI countries had smaller abdominal
      circumference, possibly indicating less fat-free mass, regardless of maternal
      life course SEP. CONCLUSION: Our results suggest that there are transgenerational
      effects of maternal past socio-economic conditions on offspring size and body
      composition at birth that modify the associations with present socio-economic
      factors.

PMID- 25060594
TI  - The effects of season and gender on the serum aflatoxins and ochratoxin A levels
      of healthy adult subjects from the Central Anatolia Region, Turkey.
AB  - PURPOSE: This study was undertaken to determine the effects of season and gender
      on serum aflatoxin (AF) levels (AFG1, AFB1, AFG2 and AFB2) and ochratoxin A (OTA)
      concentrations of healthy adult population living in Central Anatolia Region of
      Turkey. METHODS: AF levels were measured by high-performance liquid
      chromatography (HPLC) and OTA levels were measured by enzyme-linked immunosorbent
      assay (ELISA) in serum samples of healthy adults (n = 233). RESULTS: In summer
      and winter, total AF levels in females were 0.98 +/- 0.10 and 0.94 +/- 0.12 ng/ml
      and in males 1.35 +/- 0.17 and 0.93 +/- 0.11 ng/ml, respectively. Male subjects
      had significantly higher serum total AF levels in summer compared with females
      (~38%). There was no marked seasonal change in AFG1, AFB1 and AFG2 concentrations
      in the whole population, except AFB2. Both of the genders had significantly
      higher OTA levels in winter compared with summer (~60%). CONCLUSIONS: Overall
      results suggest that Central Anatolia residents are continuously exposed to AFs
      and OTA. Besides, season and gender can be effective in mycotoxin exposure.

PMID- 25060596
TI  - Differential response of encapsulated nucleus pulposus and bone marrow stem cells
      in isolation and coculture in alginate and chitosan hydrogels.
AB  - Cell-based therapies may hold significant promise for the treatment of early
      stage degeneration of the intervertebral disc (IVD). Given their propensity to
      proliferate and ability to form multiple tissue types, mesenchymal stem cells
      (MSCs) have been proposed as a potential cell source to promote repair of the
      nucleus pulposus (NP). However, for any successful cell-based therapy, a carrier
      biomaterial may be essential for targeted delivery providing key biophysical and
      biochemical cues to facilitate differentiation of MSCs. Two widely used
      biomaterials for NP regeneration are chitosan and alginate. The primary objective
      of this study was to assess the influence of alginate and chitosan hydrogels on
      bone marrow stem cells (BM) and NP cells in isolation or in coculture. A
      secondary objective of this study was to investigate coculture seeding density
      effects of BM and NP cells and simultaneously explore which cell type is
      responsible for matrix formation in a cocultured environment. Porcine NP and BM
      cells were encapsulated in alginate and chitosan hydrogels separately at two
      seeding densities (4*10(6) and 8*10(6) cells/mL) or in coculture (1:1, 8*10(6)
      cells/mL). Constructs (diameter=5 mm, height=3 mm) were maintained under IVD-like
      conditions [low-glucose, low (5%) oxygen] with or without transforming growth
      factor-beta3 (TGF-beta3) supplementation for 21 days. Results demonstrated
      differential viability depending on hydrogel type. NP cells remained viable in
      both biomaterial types whereas BM viability was diminished in chitosan. Further,
      hydrogel type was found to regulate sulfated glycosaminoglycan (sGAG) and
      collagen accumulation. Specifically, alginate better supports sGAG accumulation
      and collagen type II deposition for both NP and BM cell types compared with
      chitosan. Having identified that alginate more readily supports cell viability
      and matrix accumulation, we further explored additional effects of seeding
      density ratios (NP:BM--1:1, 1:2) for coculture studies. Interestingly, in
      coculture conditions, the BM cell population declined in number while NP cells
      increased, indicating that MSCs may in fact be signaling NP cells to proliferate
      rather than contributing to matrix formation. These findings provide exciting new
      insights on the potential of MSCs for NP tissue regeneration strategies.

PMID- 25060597
TI  - Adherence to adrenal incidentaloma guidelines is influenced by radiology report
      recommendations.
AB  - INTRODUCTION: Approximately 5% of all abdominal computed tomography (CT) and
      magnetic resonance imaging (MRI) scans reveal an adrenal incidentaloma. Although
      most adrenal incidentalomas are benign non-functioning adenomas, lesions may be
      hormonally active and/or malignant. The aim of this study was to determine
      adherence to recommended international guidelines and potential influencing
      factors when an adrenal incidentaloma is identified in routine clinical practice.
      METHODS: A retrospective study was performed of all CT and MRI reports from
      December 2009 to December 2011 using a key phrase search to identify patients
      with an incidental adrenal lesion. RESULTS: A total of 125 patients with
      incidental adrenal lesions were identified, of which 74 patients were considered
      appropriate for further endocrine/radiological workup. Of the 74 patients, only
      19 (26%) were initially referred to the endocrine service for investigation;
      21/74 (28%) had complete biochemical workup and 24/74 (32%) had imaging follow-up
      arranged. The reporting radiologist provided advice for follow-up in 31/74 (42%),
      and action was more likely to be taken when this recommendation was given. Follow
      up of the patients who had not received investigation was attempted resulting in
      assessment of a further 23 patients. Of the 44 patients who have undergone full
      assessment, four patients were found to have clinically significant lesions (one
      each of: Cushing's syndrome, phaeochromocytoma, Conn's syndrome and
      plasmacytoma). CONCLUSION: This study suggests that the majority of adrenal
      incidentalomas may not be investigated according to current international
      guidelines. The recommendations by the reporting radiologist appear to influence
      whether a patient is referred for further investigation.

PMID- 25060598
TI  - Routine Activities Preceding Adolescent Sexual Abuse of Younger Children.
AB  - Adolescent abuse of younger children has long been recognized, but empirical
      research on the circumstances of this phenomenon is rare. This article examines
      how adolescent offenders find and gain access to victims, work out time alone
      with them, and set up or exploit settings for sexual contact. Prior researchers
      learned that adult sex offenders use certain routine activities to perform these
      tasks. The current research inquires whether adolescent offenders are similar. We
      administered Kaufman's Modus Operandi Questionnaire to a sample of 116 Canadian
      adolescent males undergoing treatment for a sexual offense against a child.
      Adolescent offenders follow routines similar to adults but are better able to use
      games and activities as a prelude to sexual abuse. We discuss how routine legal
      activities set the stage for activities and should be considered when devising
      situational prevention strategies.

PMID- 25060599
TI  - Perspectives on personalized nutrition for obesity.

PMID- 25060600
TI  - Don't touch the gadget because it's hot! Mothers' and children's behavior in the
      presence of a contrived hazard at home: implications for supervising children.
AB  - OBJECTIVE: This study compared boys' with girls' hazard-directed behaviors at
      home when the mother was present and absent from the room. METHODS: Videos were
      coded for how children reacted to a contrived burn hazard ('Gadget'), maternal
      verbalizations to children about the hazard, and children's compliance with
      directives to avoid the hazard. Children's behavioral attributes (risk-taking
      tendency, inhibitory control) and maternal permissive parenting style were also
      measured. RESULTS: Boys engaged in more hazard-directed behaviors when the mother
      was present than absent, whereas girls' risk behaviors did not vary with
      caregiver presence and was comparable with how boys behaved when the parent was
      absent. Mothers emphasized reactive communications, and boys received
      significantly more of these than girls. Permissiveness was associated with fewer
      statements explaining about safety. Children high in inhibitory control showed
      fewer hazard-directed behaviors and greater compliance with parent
      communications, whereas those high in risk-taking propensity showed more hazard
      directed behaviors and less compliance. CONCLUSIONS: The hazard-directed
      behaviors of boys and girls vary with caregiver context, with boys reacting to
      parent presence with increased risk taking. Depending on child attributes,
      different supervision patterns are needed to keep young children safe in the
      presence of home hazards.

PMID- 25060601
TI  - Commentary: The Wright Ross Salk Award: Reflection on a strong foundation leading
      to the robust future of pediatric psychology.

PMID- 25060602
TI  - Investigation of gender role behaviors in boys with hypospadias: comparative
      study with unaffected boys and girls.
AB  - The purpose of the study was (1) to investigate gender role behaviors of boys
      with hypospadias compared with groups of unaffected boys and girls using parental
      reports and direct observations; and (2) to directly observe effects of
      socialization (mothers' presence) on children's gender role behaviors. Ages of 19
      children with hypospadias ranged from 3 to 7 years, and each of them were matched
      to controls of unaffected boys and girls by age. All the children participated
      with their mothers. Children's gender role behaviors and their mothers' behaviors
      were evaluated using an observation coding system. Mothers also completed
      questionnaires regarding their children's gender role behaviors. Results
      indicated no atypical gender role behavior for the boys with hypospadias and no
      direct effects of socialization on their gender role behaviors. However,
      differences were found in negative communicative behaviors between boys with
      hypospadias and unaffected boys, suggesting a possible role of socialization.

PMID- 25060603
TI  - A transcription factor links growth rate and metabolism in the hypersaline
      adapted archaeon Halobacterium salinarum.
AB  - Co-ordinating metabolism and growth is a key challenge for all organisms. Despite
      fluctuating environments, cells must produce the same metabolic outputs to
      thrive. The mechanisms underlying this 'growth homeostasis' are known in bacteria
      and eukaryotes, but remain unexplored in archaea. In the model archaeon
      Halobacterium salinarum, the transcription factor TrmB regulates enzyme-coding
      genes in diverse metabolic pathways in response to glucose. However, H. salinarum
      is thought not to catabolize glucose. To resolve this discrepancy, we demonstrate
      that TrmB regulates the gluconeogenic production of sugars incorporated into the
      cell surface S-layer glycoprotein. Additionally, we show that TrmB-DNA binding
      correlates with instantaneous growth rate, likely because S-layer glycosylation
      is proportional to growth. This suggests that TrmB transduces a growth rate
      signal to co-regulated metabolic pathways including amino acid, purine, and
      cobalamin biosynthesis. Remarkably, the topology and function of this growth
      homeostatic network appear conserved across domains despite extensive alterations
      in protein components. 

PMID- 25060604
TI  - Verapamil decreases the glucose-lowering effect of metformin in healthy
      volunteers.
AB  - AIM: The organic cation transporter 1 (OCT1) plays a key role in the cellular
      transport of metformin and its subsequent glucose-lowering effect. A recent non
      clinical study reported that metformin uptake into hepatocytes is regulated via
      OCT1, and that uptake was strongly inhibited by verapamil. Therefore, we
      investigated the effects of verapamil co-administration on the pharmacokinetics
      and pharmacodynamics of metformin in humans. METHODS: We evaluated the
      pharmacokinetics and the anti-hyperglycaemic effects of metformin using an oral
      glucose tolerance test (OGTT) in 12 healthy participants, before (day 1) and
      after metformin treatment (day 2), and again on days 15 and 16 after co
      administration with verapamil. RESULTS: Verapamil inhibited the ability of
      metformin to reduce maximum blood glucose concentrations (DeltaGmax ) by 62.5% (P
      = 0.008) and decreased the area under the glucose concentration-time curve
      (DeltaAUCgluc ) by 238% (P = 0.015). However, verapamil did not significantly
      alter the Cmax and the AUC of metformin, nor its renal clearance. CONCLUSIONS:
      Our results suggest that verapamil remarkably decreases the glucose-lowering
      effect of metformin, possibly by acting as a competitive inhibitor of OCT1.

PMID- 25060605
TI  - Autosomal recessive mutations in the COL2A1 gene cause severe spondyloepiphyseal
      dysplasia.

PMID- 25060606
TI  - In-office distal Symes lesser toe amputation: a safe, reliable, and cost
      effective treatment of diabetes-related tip of toe ulcers complicated by
      osteomyelitis.
AB  - Diabetes-related tip of lesser toe ulcers have typically been associated with
      both underlying hammertoe contracture and peripheral neuropathy. The combination
      of digital deformity and neuropathy commonly results in non-healing, deep sores
      that frequently become complicated by osteomyelitis. We report on a well-known,
      but poorly reported, technique for surgical management of non-healing tip of
      lesser toe ulcers. After approval by the institutional review board, a review was
      performed of consecutive patients who had undergone office-based distal Symes toe
      amputation for a non-healing tip of lesser toe ulcer from January 2007 to
      December 2012. A variety of clinical, laboratory, and radiographic data were
      collected. A total of 48 consecutive patients (48 toe ulcers) were identified for
      inclusion in the present study. All patients had ulcers at the time of surgery,
      and no patient developed repeat ulceration of the involved digit postoperatively.
      Of the 48 patients, 44 (92%) had hammertoe deformity preoperatively. Also, 30
      patients (63%) had positive probe-to-bone results, and 29 (97%) of these patients
      had culture or histologic findings positive for osteomyelitis. Of the 48 patients
      (48 ulcers), 73% had positive bone cultures, 69% had positive pathologic findings
      demonstrating osteomyelitis, and 100% had clean margins. Methicillin-resistant
      Staphylococcus epidermidis was the most common pathogen isolated (13 of 48, 27%).
      No patient required additional amputation related to the operative digit. The
      mean follow-up period was 28.79 months. Our results have shown that in-office
      distal Symes lesser toe amputation is a safe, reliable, and likely cost-effective
      treatment of non-healing tip of lesser toe ulcers complicated by osteomyelitis.
      This office-based procedure allows bone biopsy diagnosis, removes the non-healing
      ulcer, confirms clear margins regarding the osteomyelitis, and addresses the
      underlying toe deformity to minimize the chances of repeat ulceration.

PMID- 25060607
TI  - Pigmented Onychomatricoma: A Rare Pigmented Nail Unit Tumor Presenting as
      Longitudinal Melanonychia That Has Potential for Misdiagnosis as Melanoma.
AB  - Pigmented onychomatricoma is a rare nail unit tumor that can clinically mimic
      nail unit melanoma. We report the case of a 63-year-old male with new-onset
      longitudinal melanonychia involving his right second toe. An excisional biopsy
      was performed and demonstrated pigmented onychomatricoma. We present this case to
      alert clinicians of this rare nail unit tumor and the importance of
      clinicopathologic correlation to avoid misdiagnosis. 

PMID- 25060608
TI  - Identification of a novel nonsense mutation in the ligand-binding domain of the
      vitamin d receptor gene and clinical description of two greek patients with
      hereditary vitamin d-resistant rickets and alopecia.
AB  - BACKGROUND/AIMS: We analyzed the vitamin D receptor (VDR) gene in 2 Greek
      patients who exhibited the classical features of hereditary vitamin D-resistant
      rickets (HVDRR) type II, including severe bone deformities and alopecia. We also
      describe the clinical phenotypes and the response to treatment of our patients.
      METHODS: Genomic DNA was extracted from peripheral blood samples of both
      patients. Coding region and flanking introns of VDR gDNA was amplified and direct
      sequenced. RESULTS: A unique cytosine to thymine (C>T) transition was identified
      at nucleotide position 1066 (c.1066C>T) in the ligand-binding domain of the VDR
      gene of both patients, predicting the substitution of a glutamine to a terminal
      codon at position 356 (Gln356stop). CONCLUSIONS: The novel nonsense mutation
      c.1066C>T (Gln356stop) is expected to result in a VDR protein 71 amino acids
      shorter and thus to affect the normal VDR function. In particular, the missing
      protein part alters the VDR heterodimerization with the retinoid X receptor which
      has been correlated with the presence of alopecia. Both patients were introduced
      to treatment with supraphysiological doses of 1alpha-calcidiol which improved
      their clinical phenotypes except for alopecia.

PMID- 25060609
TI  - Occurrence of Bacillus amyloliquefaciens as a systemic endophyte of vanilla
      orchids.
AB  - We report the occurrence of Bacillus amyloliquefaciens in vanilla orchids
      (Vanilla phaeantha) and cultivated hybrid vanilla (V. planifolia * V. pompona) as
      a systemic bacterial endophyte. We determined with light microscopy and
      isolations that tissues of V. phaeantha and the cultivated hybrid were infected
      by a bacterial endophyte and that shoot meristems and stomatal areas of stems and
      leaves were densely colonized. We identified the endophyte as B.
      amyloliquefaciens using DNA sequence data. Since additional endophyte-free plants
      and seed of this orchid were not available, additional studies were performed on
      surrogate hosts Amaranthus caudatus, Ipomoea tricolor, and I. purpurea. Plants of
      A. caudatus inoculated with B. amyloliquefaciens demonstrated intracellular
      colonization of guard cells and other epidermal cells, confirming the pattern
      observed in the orchids. Isolations and histological studies suggest that the
      bacterium may penetrate deeply into developing plant tissues in shoot meristems,
      forming endospores in maturing tissues. B. amyloliquefaciens produced fungal
      inhibitors in culture. In controlled experiments using morning glory seedlings we
      showed that the bacterium promoted seedling growth and reduced seedling necrosis
      due to pathogens. We detected the gene for phosphopantetheinyl transferase (sfp),
      an enzyme in the pathway for production of antifungal lipopeptides, and purified
      the lipopeptide "surfactin" from cultures of the bacterium. We hypothesize that
      B. amyloliquefaciens is a robust endophyte and defensive mutualist of vanilla
      orchids. Whether the symbiosis between this bacterium and its hosts can be
      managed to protect vanilla crops from diseases is a question that should be
      evaluated in future research.

PMID- 25060610
TI  - Monthly versus as-needed ranibizumab injections in patients with retinal vein
      occlusion: the SHORE study.
AB  - OBJECTIVE: To compare pro re nata (PRN) and monthly injections of 0.5 mg
      ranibizumab in retinal vein occlusion (RVO) patients stabilized by monthly
      injections. DESIGN: Randomized, open-label, vision-examiner masked, 15-month
      study. PARTICIPANTS: Subjects with macular edema secondary to branch or central
      RVO. METHODS: Subjects received monthly injections of 0.5 mg ranibizumab for 7
      months and those meeting stability criteria between months 7 and 14 were
      randomized (1:1) to PRN injections versus continued monthly injections. Non
      randomized (NR) subjects (never met stability criteria) received monthly
      injections. MAIN OUTCOME MEASURES: The primary endpoint was the slope of change
      in best-corrected visual acuity (BCVA) between months 7 and 15. RESULTS: There
      was no significant difference in the slope of change in BCVA between months 7 and
      15 in patients treated PRN versus those treated with monthly injections (P =
      0.509). Mean (+/- standard deviation) change from baseline BCVA in Early
      Treatment Diabetic Retinopathy Study letter score at month 15 was 21.0 +/- 14.1
      in the PRN group (n = 82) versus 18.7 +/- 14.1 in the monthly group (n = 80) and
      14.5 +/- 14.7 in NR subjects (n = 13). The percentage of subjects who achieved
      BCVA >= 20/40 at month 15 was 76.8% in the PRN group, 71.3% in the monthly group,
      and 46.2% in NR subjects. The mean (+/- standard deviation) change from baseline
      central subfield thickness was -247.8 +/- 207.5 MUm in the PRN group, -289.9 +/-
      177.2 MUm in the monthly group, and -93.2 +/- 225.2 MUm in NR subjects. There
      were no significant differences in mean BCVA gains or central subfield thickness
      reductions at month 15 between the PRN and monthly injection groups (all > 0.05).
      CONCLUSIONS: After edema resolution from 7 or more monthly ranibizumab injections
      in RVO subjects, visual outcomes at month 15 were excellent and not significantly
      different in subjects treated PRN versus those who continued monthly injections.

PMID- 25060611
TI  - Pampagilas: Methamphetamine in the everyday economic lives of underclass male
      youths in a Philippine port.
AB  - BACKGROUND: Amid growing concerns about methamphetamine use in Southeast Asia,
      one important lesson from the field is that the drug serves various 'functions'
      for its users. The current study explores the functions of methamphetamine
      (locally known as shabu) in the economic and social lives of a community of
      underclass young men in a Philippine port. METHODS: Semi-structured interviews
      and focus group discussions were conducted with 20 young men (aged 18-25), most
      of whom worked as street vendors. Participant observation was carried out for 12
      months. FINDINGS: Methamphetamine use led these young men to experience various
      desirable effects: increased strength and confidence, disinhibition, insomnia,
      and an overall improvement of mood that facilitates performance at work and
      social bonding in their peer group. Methamphetamine, in short, is seen as a
      'performance enhancer' (pampagilas). While young people were aware of the legal,
      economic, and physiologic risks of using methamphetamine, these risks were
      outweighed by the perceived benefits in the context of an informal economy where
      opportunities are limited. CONCLUSION: Drug policies and programs in the
      Philippines must acknowledge the economic and social role of methamphetamine in
      the daily lives of young men. This group need skills training and opportunities
      to move out of an informal economy that generates the demand for drugs to enhance
      performance - necessary in an arena where performance means survival.

PMID- 25060612
TI  - Governance in EU illicit drugs policy.
AB  - This commentary represents the authors' views on EU governance in illicit drug
      policy, a field in which they were active for more than 10 years between them. EU
      drug policy has a narrow legal basis in the European Treaties and is mostly non
      binding. The main policy instruments are 8-year EU Drug Strategies, underpinned
      by 4-year Action Plans which set out specific objectives at national, EU or
      international level. The approach that guides EU drug policy is known as the
      'balanced approach'. It is remarkably restrained and reflects the reality that
      very few Member States have either the socio-political culture or the resources
      to consistently apply the punitive sanctions foreseen by the UN conventions. An
      important feature of EU governance in the field of drugs is the proactive support
      that is provided to non-governmental organisations both within the EU as well as
      in accession, associated or third countries. At a global level, the EU is a major
      financial aid donor also in this field. This position is not however reflected in
      corresponding political clout for the EU within the UN system. EU governance on
      drugs has made it possible for many of its Member States to accommodate the
      problem rather than to "solve" what by all the evidence from the last 100 years
      may well be insoluble, at least by means of criminalisation and prohibition. The
      big question is where EU drug policy is headed in the next few years. The EU has
      been promoting measures and practices that target real problems. It has done so
      without indulging too much in unhelpful rhetoric. However, like all successful
      formulae this one also has a sell-by date. EU governance in the field of drugs
      cannot afford to stand still. It needs to find a second wind. 

PMID- 25060613
TI  - Effects of transnational migration on drug use: an ethnographic study of Nepali
      female heroin users in Hong Kong.
AB  - BACKGROUND: Past studies of female drug users in South Asia tend to focus on
      their plights, for instance, how they have been driven to drug use and encounter
      more problems than their male counterparts, such as HIV/AIDS and sexual abuse.
      Few studies focus on their active role--how they actively make use of resources
      in the external environment to construct their desired femininity through drug
      consumption. Furthermore, little is known about the situation of female South
      Asian drug users who are living overseas. This paper is a study of transnational
      migration, drug use and gender--how transnational migration influences the drug
      use of female transnational migrants. METHODS: An 18-month ethnography has been
      carried out in a Nepali community in Hong Kong and 13 informants were
      interviewed. Data were coded and analyzed by using the grounded-theory approach.
      Themes related to the drug use of the female Nepali heroin users were identified.
      RESULTS: The findings show that there are three important themes that
      significantly affect the drug use of female Nepali heroin users, which include
      (1) their relationships with intimate partners, (2) their means of support, and
      (3) their legal status in migration. CONCLUSIONS: The findings are consistent
      with the concept of post-structuralism in gender and transnationalism theories.
      Female Nepali heroin users in Hong Kong are neither active agents nor passive
      victims; their active/passive role is largely dependent on their reconfigured
      opportunities and constraints in transnational migration. Thus, transnationalism
      should be taken as an important perspective to study the situation of female drug
      users in a globalized context.

PMID- 25060616
TI  - Introduction to the pediatric radiology research forum.

PMID- 25060615
TI  - Meniscal pathology in children: differences and similarities with the adult
      meniscus.
AB  - The normal meniscus undergoes typical developmental changes during childhood,
      reaching a mature adult appearance by approximately 10 years of age. In addition
      to recognizing normal meniscal appearances in children, identifying abnormalities
      - such as tears and the different types of discoid meniscus and meniscal cysts,
      as well as the surgical implications of these abnormalities - is vital in
      pediatric imaging. The reported incidence of meniscal tears in adolescents and
      young adults has increased because of increased sports participation and more
      widespread use of MRI. This review discusses the normal appearance of the
      pediatric meniscus, meniscal abnormalities, associated injuries, and prognostic
      indicators for repair.

PMID- 25060617
TI  - A new research paradigm for pediatric radiology-can we climb the pyramid?

PMID- 25060618
TI  - Basic science research in pediatric radiology - how to empower the leading edge
      of our field.
AB  - Basic science research aims to explore, understand and predict phenomena in the
      natural world. It spurs the discovery of fundamentally new principles and leads
      to new knowledge and new concepts. By comparison, applied research employs basic
      science knowledge toward practical applications. In the clinical realm, basic
      science research and applied research should be closely connected. Basic science
      discoveries can build the foundation for a broad range of practical applications
      and thereby bring major benefits to human health, education, environment and
      economy. This article explains how basic science research impacts our field, it
      describes examples of new research directions in pediatric imaging and it
      outlines current challenges that we need to overcome in order to enable the next
      groundbreaking discovery. 

PMID- 25060619
TI  - Comparative effectiveness research in pediatric radiology.
AB  - Comparative effectiveness research is designed to help patients, physicians and
      policymakers choose the best medical option among alternative diagnostic and
      interventional strategies. In this commentary, we provide a brief overview of
      comparative effectiveness research, discuss some of the challenges to applying it
      in pediatric radiology, and give several reasons behind the continued push for
      more comparative effectiveness research by governmental and other funding
      agencies. 

PMID- 25060622
TI  - Outpatient treatment costs and their potential impact on cancer care.
AB  - Cancer creates a tremendous financial burden. Cancer-related costs are
      categorized into direct, indirect, and psychosocial costs. Although there have
      been many reports on medical care costs, which are direct, those on other costs
      are extremely scarce. We estimated travel time and costs required for cancer
      patients to receive outpatient treatment. We studied 521 cancer patients
      receiving anti-cancer treatment between February 2009 and December 2012 at the
      Outpatient Chemotherapy Center of Teikyo University Chiba Medical Center. Address
      data were extracted from Data Warehouse electronic medical records, and travel
      distance and time required for outpatient treatment were calculated via MapInfo
      and ACT Distance Calculator Package. Transportation costs were estimated on the
      basis of Y274 (=$3.00) per kilometer. The study design was approved by an ethics
      review board of Teikyo University (12-851). Average round-trip travel distance,
      time, and cost for all patients were 26.7 km, 72.5 min, and Y7,303 ($79.99),
      respectively. Cancer patients incurred a travel cost of Y4000-Y9000 ($40.00 to
      $100.00) for each outpatient treatment. With population aging, seniors living
      alone and senior households are increasing, and outpatient visits are becoming a
      common burden.

PMID- 25060624
TI  - A new dataset of spermatogenic vs. oogenic transcriptomes in the nematode
      Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans is an important model for studies of germ
      cell biology, including the meiotic cell cycle, gamete specification as sperm or
      oocyte, and gamete development. Fundamental to those studies is a genome-level
      knowledge of the germline transcriptome. Here, we use RNA-Seq to identify genes
      expressed in isolated XX gonads, which are approximately 95% germline and 5%
      somatic gonadal tissue. We generate data from mutants making either sperm [fem
      3(q96)] or oocytes [fog-2(q71)], both grown at 22 degrees . Our dataset
      identifies a total of 10,754 mRNAs in the polyadenylated transcriptome of XX
      gonads, with 2748 enriched in spermatogenic gonads, 1732 enriched in oogenic
      gonads, and the remaining 6274 not enriched in either. These spermatogenic,
      oogenic, and gender-neutral gene datasets compare well with those of previous
      studies, but double the number of genes identified. A comparison of the
      additional genes found in our study with in situ hybridization patterns in the
      Kohara database suggests that most are expressed in the germline. We also query
      our RNA-Seq data for differential exon usage and find 351 mRNAs with sex-enriched
      isoforms. We suggest that this new dataset will prove useful for studies focusing
      on C. elegans germ cell biology. 

PMID- 25060625
TI  - Ploidy-regulated variation in biofilm-related phenotypes in natural isolates of
      Saccharomyces cerevisiae.
AB  - The ability of yeast to form biofilms contributes to better survival under
      stressful conditions. We see the impact of yeast biofilms and "flocs" (clumps) in
      human health and industry, where forming clumps enables yeast to act as a natural
      filter in brewing and forming biofilms enables yeast to remain virulent in cases
      of fungal infection. Despite the importance of biofilms in yeast natural
      isolates, the majority of our knowledge about yeast biofilm genetics comes from
      work with a few tractable laboratory strains. A new collection of sequenced
      natural isolates from the Saccharomyces Genome Resequencing Project enabled us to
      examine the breadth of biofilm-related phenotypes in geographically,
      ecologically, and genetically diverse strains of Saccharomyces cerevisiae. We
      present a panel of 31 haploid and 24 diploid strains for which we have
      characterized six biofilm-related phenotypes: complex colony morphology, complex
      mat formation, flocculation, agar invasion, polystyrene adhesion, and
      psuedohyphal growth. Our results show that there is extensive phenotypic
      variation between and within strains, and that these six phenotypes are primarily
      uncorrelated or weakly correlated, with the notable exception of complex colony
      and complex mat formation. We also show that the phenotypic strength of these
      strains varies significantly depending on ploidy, and the diploid strains
      demonstrate both decreased and increased phenotypic strength with respect to
      their haploid counterparts. This is a more complex view of the impact of ploidy
      on biofilm-related phenotypes than previous work with laboratory strains has
      suggested, demonstrating the importance and enormous potential of working with
      natural isolates of yeast. 

PMID- 25060627
TI  - Attenuated psychosis syndrome: need for debate on a new disorder.
AB  - This 'pro' statement of the controversial issue, defending the need for a new
      disorder classification of attenuated psychosis syndrome (APS), provides data
      supporting the clinical validity of this category and responds to the most
      frequently asserted criticisms. It provides arguments why APS is not
      pathologizing non-ill behaviors and is not stigmatizing for those affected but
      rather they merit clinical attention for what is already manifest. It also argues
      against the view that establishing the diagnostic category of APS results in an
      unreasoned excessive use of antipsychotic medications but rather encourages
      prevention and early intervention programs. Finally, bodies of research are
      presented which could contribute to further validating APS and provide the
      preconditions for moving this category from Section 3 to Section 2 of DSM-5.1.

PMID- 25060626
TI  - A multi-molecular marker assessment of organic pollution in shore sediments from
      the Rio de la Plata Estuary, SW Atlantic.
AB  - Organic pollution was evaluated in surface sediments along the middle portion of
      the Rio de la Plata Estuary, SW Atlantic. A multi-molecular marker approach was
      performed to identify major sources of organic compounds using diagnostic
      indices. The relative contribution of different sources of hydrocarbons was
      quantified by source apportionment employing Principal Component
      Analysis/Multiple Linear Regression (PCA/MLR) as chemometric technique. All
      molecular markers indicated high chronic organic pollution in the stations of
      Montevideo Bay. Main sources of aliphatic and polycyclic aromatic hydrocarbons
      were petroleum inputs and combustion, due to oil transport and refinement,
      harbour activities and vehicular emissions. Major sources of linear alkylbenzenes
      and steroids were industrial and domestic sewage. Although, significant
      anthropogenic inputs, a natural footprint of terrestrial higher plants
      contribution was recognized. Multi-molecular marker and comprehensive assessments
      can improve the establishment of more precise regulation actions to reduce
      pollution levels. 

PMID- 25060628
TI  - Histological features and severity of oxaliplatin-induced liver injury and
      clinical associations.
AB  - OBJECTIVE: Oxaliplatin, a component of chemotherapy for colorectal carcinoma
      liver metastases, can result in hepatic sinusoidal injury; rarely, the injury is
      fatal. The manifestations of injury are variable. There are no known predictors
      of susceptibility and outcome. A semi-quantitative system for assessing
      histological features in non-tumor liver was designed to compare with clinical
      short-term and long-term outcomes. METHODS: A review of 47 patients with
      metastatic colorectal carcinoma who received liver resection utilizing a system
      for an aggregate liver injury score (0-4) included hepatocellular and sinusoidal
      features. Immunohistochemistry (IHC) for aberrant capillarization was included.
      The proliferation of hepatocytes and sinusoidal lining cells was evaluated with
      Ki-67 stain. RESULTS: In total, 32 (68.1%) cases showed light microscopic lesions
      of oxaliplatin-induced liver injury, in which 26 were moderate to severe.
      Elevated preoperative aspartate aminotransferase (AST) and alkaline phosphatase
      levels were noted with higher injury scores (P = 0.01). Patients with higher
      injury scores had no significant increase in short-term postoperative
      complications, with one notable exception, who died of liver failure 10 months
      postoperatively. Increased CD34 expression was associated with higher injury
      scores (P = 0.00004), and abnormal AST levels (P = 0.04). Preoperative use of
      bevacizumab was not associated with lower injury scores. Steatosis was correlated
      with body mass index (P = 0.052) but not with exposure to oxaliplatin,
      bevacizumab or irinotecan. CONCLUSIONS: The proposed liver injury scoring system
      encompasses the spectrum of sinusoidal and hepatocellular lesions in oxaliplatin
      induced liver injury and is correlated with serum liver enzyme levels in this
      group. Most patients recovered without complications during the 93-month follow
      up, indicating that these lesions are reversible.

PMID- 25060629
TI  - Heat shock protein 90 maintains the stability and function of transcription
      factor Broad Z7 by interacting with its Broad-Complex-Tramtrack-Bric-a-brac
      domain.
AB  - Heat shock protein 90 (Hsp90) is a highly conserved chaperone protein that
      interacts with various client proteins to mediate their folding and stability.
      The Broad-Complex-Tramtrack-Bric-a-brac (BTB) domain, also known as poxvirus and
      zinc finger (POZ) domain, exists widely in different proteins and is highly
      conserved. However, the stability mechanism of BTB domain-containing proteins has
      not been fully understood. Co-immunoprecipitation and a protein pull-down assay
      were performed to investigate the interaction between Hsp90 and the transcription
      factor Broad isoform Z7 (BrZ7) in vivo and in vitro. The middle domain of Hsp90
      directly associated with the BTB domain of BrZ7. The Hsp90 inhibitor 17
      (Allylamino)-17-demethoxygeldanamycin (17-AAG) interrupted the interaction
      between Hsp90 and BrZ7 and decreased the protein level of BrZ7 but did not affect
      the mRNA level of BrZ7. The addition of the proteasome inhibitor peptide aldehyde
      Cbz-leu-leu leucinal suppressed the 17-AAG-induced degradation of BrZ7. BTB
      domain deletion and 17-AAG treatment resulted in inhibition of BrZ7 function in
      gene expression in the 20-hydroxyecdysone and juvenile hormone pathways. These
      results reveal that the middle domain of Hsp90 associates with the BTB domain of
      BrZ7 to prevent BrZ7 degradation and maintain BrZ7 function in gene expression in
      the lepidopteran insect Helicoverpa armigera. 

PMID- 25060630
TI  - Maternal and health care workers' perceptions of the effects of exclusive
      breastfeeding by HIV positive mothers on maternal and infant health in Blantyre,
      Malawi.
AB  - BACKGROUND: HIV-positive mothers are likely to exclusively breastfeed if they
      perceive exclusive breastfeeding (EBF) beneficial to them and their infants.
      Nevertheless, very little is known in Malawi about HIV-positive mothers'
      perceptions regarding EBF. In order to effectively promote EBF among these
      mothers, it is important to first understand their perceptions on benefits of
      exclusive breastfeeding. This study therefore, explored maternal and health care
      workers' perceptions of the effects of exclusive breastfeeding on HIV-positive
      mothers' health and that of their infants. METHODS: This was a qualitative study
      within a larger project. Face-to-face in-depth interviews and focus group
      discussions using a semi- structured interview and focus group guide were
      conducted. Sixteen HIV-positive breastfeeding mothers, between 18 and 35 years
      old, were interviewed and data saturation was achieved. Two focus group
      discussions (FGDs) comprising of five and six adult women of unknown HIV status
      who were personal assistants to maternity patients, and one FGD with five nurse
      midwives working in the maternity wards of Queen Elizabeth Central Hospital in
      Blantyre, Malawi, were also conducted. Thematic content data analysis was
      utilized. RESULTS: The study revealed more positive than negative perceived
      effects of exclusive breastfeeding. However, the fear of transmitting HIV to
      infants through breast milk featured strongly in the study participants' reports
      including those of the nurse-midwives. Only one nurse-midwife and a few HIV
      positive mothers believed that EBF prevents mother-to-child transmission of HIV.
      Furthermore, participants, especially the HIV-positive mothers felt that
      exclusive breastfeeding leads to maternal ill- health and would accelerate their
      progression to full blown AIDS. CONCLUSION: While most participants considered
      exclusive breastfeeding as an important component of the wellbeing of their
      infants' health, they did not share the worldwide acknowledged benefits of
      exclusive breastfeeding in the prevention of mother-to-child transmission (PMTCT)
      of HIV. These results suggest a need for more breastfeeding education for all
      mothers, communities and nurse-midwives involved in breastfeeding counseling in
      the context of HIV infection. Maternal wellbeing promotion activities such as
      nutrition supplementation need to be included in all PMTCT of HIV programs.

PMID- 25060631
TI  - MGr1-Ag/37LRP promotes growth and proliferation of gastric cancer in vitro and in
      vivo.
AB  - Gastric carcinoma (GC) is an aggressive cancer with a poor prognosis. We
      previously reported that MGr1-Ag was involved in multidrug resistance and anti
      apoptosis in GC. However, the exact function of MGr1-Ag in GC proliferation is
      not clear. In this study, we found that MGr1-Ag was highly expressed in GC
      tissues and four GC cell lines compared with nontumor gastric tissues or gastric
      epithelial mucosa cells. The high expression of MGr1-Ag/37LRP was also consistent
      with the decreased median survival time of GC patients. We employed lenti
      mediated RNA interference technique to knock down MGr1-Ag expression in SGC7901
      and MKN45 cells, respectively, and observed its effects on GC cells growth in
      vitro and in vivo. Further study showed that knockdown of MGr1-Ag could inhibit
      GC cell proliferation by inhibiting the cell cycle S-phase entry and induced
      apoptosis. Soft agar colony formation assay indicated that the colony formation
      ability of SGC7901 and MKN45 cells decreased after lenti-MGr1-Ag small
      interfering RNA (siRNA) infection. Western blot revealed that cyclin D1 and Bcl-2
      expression were downregulated whereas p27 and Bax were upregulated in lenti-MGr
      siRNA-infected GC cells. Further study demonstrated that the proliferation effect
      of MGr1-Ag in GC is dependent on its laminin-binding region. Taken together,
      these data revealed a novel function of MGr1-Ag that can possibly be used as an
      independent prognostic factor and a potential therapeutic target for GC. 

PMID- 25060633
TI  - Towards a safe lithium-sulfur battery with a flame-inhibiting electrolyte and a
      sulfur-based composite cathode.
AB  - Of the various beyond-lithium-ion batteries, lithium-sulfur (Li-S) batteries were
      recently reported as possibly being the closest to market. However, its
      theoretically high energy density makes it potentially hazardous under conditions
      of abuse. Therefore, addressing the safety issues of Li-S cells is necessary
      before they can be used in practical applications. Here, we report a concept to
      build a safe and highly efficient Li-S battery with a flame-inhibiting
      electrolyte and a sulfur-based composite cathode. The flame retardant not only
      makes the carbonates nonflammable but also dramatically enhances the
      electrochemical performance of the sulfur-based composite cathode, without an
      apparent capacity decline over 750 cycles, and with a capacity greater than 800
      mA h(-1)  g(-1) (sulfur) at a rate of 10 C. 

PMID- 25060634
TI  - Altered Brain White Matter Integrity in Temporal Lobe Epilepsy: A TBSS Study.
AB  - BACKGROUND AND PURPOSE: The aim of this study is to explore the possible changed
      cerebral white matter regions in patients with temporal lobe epilepsy (TLE) using
      diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS).
      METHODS: Twenty TLE patients and 22 age- and gender-matched normal controls were
      included in this study. Voxel-wise analyses of multiple diffusion metrics,
      including fractional anisotropy (FA) and mean diffusivity (MD) were performed
      with TBSS. RESULTS: TLE patients exhibited significantly reduced FA in widespread
      white matter regions including bilateral limbic circuit, corpus callosum,
      thalamus, internal/external capsule, temporooccipital connections, frontotemporal
      connections; increase of MD was exhibited significantly almost in the left
      hemisphere. A significant decrease in global FA integrity was shown in epilepsy
      subjects compared to healthy controls. Furthermore, it exhibited a significant
      positive correlation between the disease duration and MD of whole brain.
      CONCLUSIONS: TLE is associated with widespread abnormalities in cerebral white
      matter tracts and these changes may have important clinical consequences.

PMID- 25060635
TI  - Analysis of transplant urgency and benefit via multiple imputation.
AB  - Missing (censored) death times for lung candidates in urgent need of transplant
      are a signpost of success for allocation policy makers. However, statisticians
      analyzing these data must properly account for dependent censoring as the sickest
      patients are removed from the waitlist. Multiple imputation allows the creation
      of complete data sets that can be used for a variety of standard analyses in this
      setting. We propose an approach to multiply impute lung candidate outcomes that
      incorporates (i) time-varying factors predicting removal from the waitlist and
      (ii) estimates of transplant urgency via restricted mean models. The measures of
      transplant urgency and benefit for individual patient profiles are discussed in
      the context of lung allocation score modeling in the USA. Marginal survival
      estimates in the event that a transplant does not occur are also provided.
      Simulations suggest that the proposed imputation method gives attractive results
      when compared with existing methods.

PMID- 25060636
TI  - Introductory paragraph -Volume 28, Issue 8.

PMID- 25060632
TI  - MicroRNA and signaling pathways in gastric cancer.
AB  - MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors by
      inhibiting the expression of target genes, some of which are either directly or
      indirectly involved with canonical signaling pathways. The relationship between
      miRNAs and signaling pathways in gastric cancer is extremely complicated. In this
      paper, we determined the pathogenic mechanism of gastric cancer related to miRNA
      expression based on recent high-quality studies and then clarified the regulation
      network of miRNA expression and the correlated functions of these miRNAs during
      the progression of gastric cancer. We try to illustrate the correlation between
      the expression of miRNAs and outcomes of patients with gastric cancer.
      Understanding this will allow us to take a big step forward in the treatment of
      gastric cancer. 

PMID- 25060637
TI  - Confounding factors in observational study: the Achilles heel.

PMID- 25060638
TI  - Preadmission quality of life can predict mortality in intensive care unit--a
      prospective cohort study.
AB  - PURPOSE: We sought to investigate whether preadmission quality of life could act
      as a predictor of mortality among patients admitted to the intensive care unit
      (ICU). MATERIALS AND METHODS: This is a prospective observational study of all
      patients above the age of 18 years admitted to the ICU with a length of stay
      longer than 24 hours. Short form 36 (SF-36) and Acute Physiology and Chronic
      Health Evaluation II (APACHE II) were used. Mortality was assessed during ICU
      admission, 30, and 90 days hereafter. RESULTS: We included 318 patients. No
      patients were lost to follow-up. Using the physical component summary of short
      form 12 (SF-12) as a predictor of ICU mortality, the area under the curve (0.70;
      confidence interval, 0.62-0.77) was comparable with that of APACHE II (0.74;
      confidence interval, 0.67-0.82). The difference between SF-12 and SF-36 was
      nonsignificant. CONCLUSIONS: Preadmission quality of life, assessed by SF-36 and
      SF-12, is as good at predicting ICU, 30-, and 90-day mortality as APACHE II in
      patients admitted to the ICU for longer than 24 hours. This indicates that
      estimated preadmission quality of life, potentially available in the pre-ICU
      setting, could aid decision making regarding ICU admission and deserves more
      attention by those caring for critically ill patients.

PMID- 25060639
TI  - Historical evolution of the brain death concept: additional remarks.

PMID- 25060640
TI  - Goal-directed therapy after cardiac surgery and the incidence of acute kidney
      injury.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of goal-directed
      therapy (GDT), after cardiac surgery, on the incidence of acute kidney injury
      (AKI). DESIGN: This is a prospective observational study designed to achieve and
      maintain maximum stroke volume for 8 hours, in patients after cardiac surgery.
      SETTING: This is a single-center study in a 15-bedded cardiothoracic intensive
      care unit (ICU). PARTICIPANTS: Participants are patients after coronary artery
      bypass grafting and/or aortic valve surgery. INTERVENTIONS: Patients in the GDT
      group received cardiac output monitoring and fluid challenges targeting an
      increase in stroke volume by at least 10%. Stroke volume maximization was
      maintained for a period of 8 hours from admission to the ICU. All other aspects
      of care were dictated by the clinical team. Patients in the standard therapy (ST)
      group had intravenous fluids in accordance with the routine practice of the unit.
      Patients were divided into the GDT and ST group dependant on availability of
      cardiac output monitors and allocation of nursing staff with training in GDT.
      Patients' data were collected prospectively in both groups. MEASUREMENTS AND MAIN
      RESULTS: One hundred twenty-three patients received GDT compared with 141
      patients in the ST group. Both groups received similar volumes of fluid (GDT,
      2905 [1367] mL vs 2704 [1393] mL; P=.09). Incidence of AKI was reduced in the GDT
      group (n=8 [6.5%] vs n=28 [19.9%]; P=.002). The median duration of hospital stay
      was 6 (4) days in the GDT group vs 7 (8) days in the ST, P=.004. CONCLUSION:
      Postoperative GDT in patients after cardiac surgery was associated with reduction
      in the incidence of AKI and a reduction in ICU and hospital duration of stay.

PMID- 25060641
TI  - X-ray crystal structure of a xanthine oxidase complex with the flavonoid
      inhibitor quercetin.
AB  - Xanthine oxidase catalyzes the sequential hydroxylation of hypoxanthine to uric
      acid via xanthine as intermediate. Deposition of crystals of the catalytic
      product uric acid or its monosodium salt in human joints with accompanying joint
      inflammation is the major cause of gout. Natural flavonoids are attractive leads
      for rational design of preventive and therapeutic xanthine oxidase inhibitors due
      to their beneficial antioxidant, anti-inflammatory, and antiproliferative
      activities in addition to their micromolar inhibitory activities toward xanthine
      oxidase. We determined the first complex X-ray structure of mammalian xanthine
      oxidase with the natural flavonoid inhibitor quercetin at 2.0 A resolution. The
      inhibitor adopts a single orientation with its benzopyran moiety sandwiched
      between Phe 914 and Phe 1009 and ring B pointing toward the solvent channel
      leading to the molybdenum active center. The favorable steric complementarity of
      the conjugated three-ring structure of quercetin with the active site and
      specific hydrogen-bonding interactions of exocyclic hydroxy groups with
      catalytically relevant residues Arg 880 and Glu 802 correlate well with a
      previously reported structure-activity relationship of flavonoid inhibitors of
      xanthine oxidase. The current complex provides a structural basis for the
      rational design of flavonoid-type inhibitors against xanthine oxidase useful for
      the treatment of hyperuricemia, gout, and inflammatory disease states. 

PMID- 25060642
TI  - Bait station devices can improve mass trapping performance for the control of the
      Mediterranean fruit fly.
AB  - BACKGROUND: The use of traps and other attract-and-kill devices in pest
      management strategies to reduce Mediterranean fruit fly populations has proved to
      be efficient. Nevertheless, many farmers are concerned about the effect of these
      devices on the trees where they are hung. Direct field observations have revealed
      that fruit damage is higher in trees with traps than in trees without them. This
      work evaluates the efficacy of different types of attract-and-kill device to
      protect fruit of the single tree on which the device is placed. RESULTS: Results
      suggested that trees with traps had at least the same fruit damage than trees
      without them. When traps were baited with protein hydrolysate, fruit damage was
      even higher than in trees without traps. However, fruit damage was significantly
      diminished when efficient bait station devices were used. CONCLUSION: Although
      mass trapping is able to control fruit fly populations as a control method, trees
      with some types of trap and bait are more susceptible to fly puncture. However,
      bait station devices reduce fruit damage in the single trees where they are hung.
      Bait stations are more efficient in fruit protection because fruit flies are
      affected as soon as they contact the device. Some recommendations for the use of
      the different attract-and-kill devices are discussed.

PMID- 25060643
TI  - Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase
      promotes breast cancer progression.
AB  - INTRODUCTION: Expression of indoleamine 2,3-dioxygenase (IDO) in primary breast
      cancer increases tumor growth and metastasis. However, the clinical significance
      of stromal IDO and the regulation of stromal IDO are unclear. METHODS:
      Metabolomics and enzyme-linked immunosorbent assay (ELISA) were used to study the
      effect of cyclooxygenase-2 (COX-2)-overexpressing breast cancer cells on IDO
      expression in co-cultured human breast fibroblasts. Biochemical inhibitors and
      short-hairpin RNA (shRNA) were used to clarify how prostaglandin E2 (PGE2)
      upregulates IDO expression. Associations of stromal IDO with clinicopathologic
      parameters were tested in tumor specimens. An orthotopic animal model was used to
      examine the effect of COX-2 and IDO inhibitors on tumor growth. RESULTS:
      Kynurenine, the metabolite generated by IDO, increases in the supernatant of
      fibroblasts co-cultured with COX-2-overexpressing breast cancer cells. PGE2
      released by cancer cells upregulates IDO expression in fibroblasts through an
      EP4/signal transducer and activator of transcription 3 (STAT3)-dependent pathway.
      Conversely, fibroblast-secreted kynurenine promotes the formation of the E
      cadherin/Aryl hydrocarbon receptor (AhR)/S-phase kinase-associated protein 2
      (Skp2) complex, resulting in degradation of E-cadherin to increase breast cancer
      invasiveness. The enhancement of motility of breast cancer cells induced by co
      culture with fibroblasts is suppressed by the IDO inhibitor 1-methyl-tryptophan.
      Pathological analysis demonstrates that upregulation of stromal IDO is a poor
      prognosis factor and is associated with of COX-2 overexpression. Co-expression of
      cancer COX-2 and stromal IDO predicts a worse disease-free and metastasis-free
      survival. Finally, COX-2 and IDO inhibitors inhibit tumor growth in vivo.
      CONCLUSION: Integration of metabolomics and molecular and pathological approaches
      reveals the interplay between cancer and stroma via COX-2, and IDO promotes tumor
      progression and predicts poor patient survival.

PMID- 25060644
TI  - CLIC1 functional expression is required for cAMP-induced neurite elongation in
      post-natal mouse retinal ganglion cells.
AB  - During neuronal differentiation, axonal elongation is regulated by both external
      and intrinsic stimuli, including neurotropic factors, cytoskeleton dynamics,
      second messengers such as cyclic adenosine monophosphate (cAMP), and neuronal
      excitability. Chloride intracellular channel 1 (CLIC1) is a cytoplasmic
      hydrophilic protein that, upon stimulation, dimerizes and translocates to the
      plasma membrane, where it contributes to increase the membrane chloride
      conductance. Here, we investigated the expression of CLIC1 in primary hippocampal
      neurons and retinal ganglion cells (RGCs) and examined how the functional
      expression of CLIC1 specifically modulates neurite outgrowth of neonatal murine
      RGCs. Using a combination of electrophysiology and immunohistochemistry, we found
      that CLIC1 is expressed in hippocampal neurons and RGCs and that the chloride
      current mediated by CLIC1 is required for maintaining growth cone morphology and
      sustaining cAMP-stimulated neurite elongation in dissociated immunopurified RGCs.
      In cultured RGCs, inhibition of CLIC1 ionic current through the pharmacological
      blocker IAA94 or a specific anti-CLIC1 antibody directed against its
      extracellular domain prevents the neurite outgrowth induced by cAMP. CLIC1
      mediated chloride current, which results from an increased open probability of
      the channel, is detected only when cAMP is elevated. Inhibition of protein kinase
      A prevents such current. These results indicate that CLIC1 functional expression
      is regulated by cAMP via protein kinase A and is required for neurite outgrowth
      modulation during neuronal differentiation. Using a combination of
      electrophysiology and immunohistochemistry, we found that the chloride
      intracellular channel 1 (CLIC1) protein modulates the speed of neurite growth.
      The chloride current mediated by CLIC1 is essential for maintaining growth cone
      morphology and is required for sustaining cAMP-stimulated neurite elongation in
      dissociated immunopurified neurons. The presence of either the CLIC1 current
      blocker IAA94 or the anti-CLIC1 antibody inhibits neurite growth of Retina
      Ganglion Cells cultured in the presence of 10 micromolar forskolin for 24 h. 

PMID- 25060646
TI  - Highly uniform and reproducible surface enhanced Raman scattering on air-stable
      metallic glassy nanowire array.
AB  - Preparation of surface enhanced Raman scattering (SERS) nanostructures with both
      high sensitivity as well as high reproducibility has always been difficult and
      costly for routine SERS detection. Here we demonstrate air-stable metallic glassy
      nanowire arrays (MGNWAs), which were prepared by a cheap and rapid die
      nanoimprinting technique, could exhibit high SERS enhancement factor (EF) as well
      as excellent reproducibility. It shows that Pd(40.5)Ni(40.5)P(19) MGNWA with
      nanowires of 55 nm in diameter and 100 nm in pitch possesses high SERS activity
      with an EF of 1.1 * 10(5), which is 1-3 orders of magnitudes higher than that of
      the reported crystal Ni-based nanostructures, and an excellent reproducibility
      with a relative standard deviation of 9.60% measured by 121 points over an area
      of 100 MUm*100 MUm. This method offers an easy, rapid, and low-cost way to
      prepare highly sensitive and reproducible SERS substrates and makes the SERS more
      practicable.

PMID- 25060645
TI  - Health impact of the 2008 cold spell on mortality in subtropical China: the
      climate and health impact national assessment study (CHINAs).
AB  - BACKGROUND: Many studies have investigated heat wave related mortality, but less
      attention has been given to the health effects of cold spells in the context of
      global warming. The 2008 cold spell in China provided a unique opportunity to
      estimate the effects of the 2008 cold spell on mortality in subtropical regions,
      spatial heterogeneity of the effects, stratification effect and added effects
      caused by sustained cold days. METHODS: Thirty-six study communities were
      selected from 15 provinces in subtropical China. Daily mortality and
      meteorological data were collected for each community from 2006 to 2010. A
      distributed lag linear non-linear model (DLNM) with a lag structure of up to 27
      days was used to analyze the association between the 2008 cold spell and
      mortality. Multivariate meta-analyses were used to combine the cold effects
      across each community. RESULTS: The 2008 cold spell increased mortality by 43.8%
      (95% CI: 34.8% ~ 53.4%) compared to non-cold spell days with the highest effects
      in southern and central China. The effects were more pronounced for respiratory
      mortality (RESP) than for cardiovascular (CVD) or cerebrovascular mortality
      (CBD), for females more than for males, and for the elderly aged >=75 years old
      more than for younger people. Overall, 148,279 excess deaths were attributable to
      the 2008 cold spell. The cold effect was mainly from extreme low temperatures
      rather than sustained cold days during this 2008 cold spell. CONCLUSIONS: The
      2008 cold spell increased mortality in subtropical China, which was mainly
      attributable to the low temperature rather than the sustained duration of the
      cold spell. The cold effects were spatially heterogeneous and modified by
      individual-specific characteristics such as gender and age.

PMID- 25060647
TI  - Arsenic toxicity in rice with special reference to speciation in Indian grain and
      its implication on human health.
AB  - BACKGROUND: Rice is a potentially important route of human exposure to arsenic,
      especially in populations with rice-based diets. However, arsenic toxicity varies
      greatly with species. The initial purpose of the present study was to evaluate
      arsenic speciation in rice. RESULTS: It appeared very clear from the present
      study that inorganic arsenic shared maximum arsenic load in rice straw while in
      grains it is considerably low. As species recovered from rice grain and straw are
      principally As(III) and As(V) with a small amount of dimethylarsenic acid (DMA)
      and almost non-detectable monomethylarsonic acid (MMA) and arsenobetain (AsB).
      Discussion of the health risk of As in rice has largely been based on its
      inorganic arsenic content because these species have generally been considered to
      be more toxic than MMA and DMA and can be directly compared to As in drinking
      water, assuming equal bioavailability of inorganic As in the rice matrix and in
      water. The maximum dietary risk of exposure to inorganic arsenic through
      transplanted boro paddy in the present experiment was calculated to be almost
      1706% of the provisional tolerable weekly intake for an adult of 60 kg body
      weight. CONCLUSION: As species recovered from boro rice grain and straw are
      principally As(III) and As(V) with a small amount of DMA and almost non
      detectable MMA and AsB. Reductions in total As load through organic amendments in
      boro rice grain and straw samples were manifested predominately through reduced
      accumulations of inorganic As species [As(III) and As(V)], between which As(V)
      accounted for the larger share.

PMID- 25060648
TI  - Val158Met polymorphism of COMT gene and Parkinson's disease risk in Asians.
AB  - In previous study, we have found the catechol-O-methyltransferase (COMT)
      Val158Met polymorphism as an associated risk factor for Parkinson's disease (PD)
      in Asian rather than Caucasian populations. The aim of this study was to further
      evaluate the associations of PD risk with COMT polymorphisms in different Asian
      populations. We carried out a retrieval of studies that investigated associations
      between COMT Val158Met polymorphism and PD risk in Asians, and included the study
      if it met the eligibility criteria. Stata version 12.0 was used to analyze the
      data. A total of 13 studies including 1,834 patients and 2,298 controls were
      included. The overall result indicated that COMT Val158Met polymorphism was
      significantly associated with the risk of PD in Asians (AA vs others: OR = 1.58,
      95 % CI 1.26-1.97, p < 0.001; GG vs AA: OR = 0.63, 95 % CI 0.47-0.85, p = 0.002;
      AA vs GA: OR = 1.58, 95 % CI 1.24-2.00, p < 0.001). In Japanese population, the
      homozygote AA tends to increase the risk of PD (AA vs others: OR = 1.54, 95 % CI
      1.10-2.15, p = 0.012; AA vs GA: OR = 1.61, 95 % CI 1.14-2.29, p = 0.008). This
      study showed that the Val158Met polymorphism of COMT gene may be associated with
      PD in Japanese rather than Chinese population. Further studies are needed to
      confirm this association in more ethnicities. 

PMID- 25060649
TI  - PARK2 presenting as a disabling peripheral axonal neuropathy.

PMID- 25060650
TI  - Predictors of outcome of myasthenic crisis.

PMID- 25060651
TI  - Efficacy of high dose methylprednisolone in a patient with cervical dystonia and
      blepharospasm and Sjogren's syndrome.

PMID- 25060652
TI  - Biofilm formation on the surface of modern implant abutment materials.
AB  - OBJECTIVE: To investigate the formation of biofilms on the surface of materials
      applied for the fabrication of implant abutments. MATERIAL AND METHODS: Specimens
      were prepared from the implant abutment materials titanium, zirconia, and
      polyetheretherketone (PEEK); specimens made from polymethylmethacrylate (PMMA)
      were used for reference. All specimens were polished to high gloss using silicon
      carbide paper; surface roughness was determined using profilometry, and surface
      free energy was calculated from contact angle measurements. After the simulation
      of salivary pellicle formation, multispecies biofilm formation was initiated by
      exposing the specimens to a suspension of Streptococcus gordonii, Streptococcus
      mutans, Actinomyces naeslundii, and Candida albicans for either 20 or 44 h.
      Viable microbial biomass adherent to the specimens (n = 10 per material and
      incubation time) and the percentage of dead microorganisms in the different
      biofilms (n = 5, accordingly) were determined. RESULTS: Significantly lower
      surface roughness was identified for PEEK and PMMA than for zirconia and titanium
      (P < 0.001); surface free energy was significantly lower for zirconia than for
      PEEK (P = 0.038). Significantly higher viable biomass and a significantly higher
      percentage of dead microorganisms were identified after 44 h than after 20 h of
      biofilm formation (P < 0.001, respectively); after 20 h, PEEK surfaces harbored
      significantly lower viable biomass than the surfaces of the other materials (P <
      0.0125). After 44 h, significant differences were identified in the percentage of
      dead microorganisms organized in the biofilms on the different materials (P =
      0.012). CONCLUSIONS: Within the limitations of a laboratory study, the results
      suggest that biofilm formation on the surface of PEEK is equal or lower than on
      the surface of conventionally applied abutment materials such as zirconia and
      titanium. However, clinical studies are necessary to corroborate these
      preliminary results.

PMID- 25060653
TI  - Staff and parents are discriminators for outcomes in neonatal intensive care
      units.
AB  - AIM: We investigated the associations between staff work characteristics,
      parents' experiences and a number of medical outcome measures. METHODS: This
      explorative multicentre study took place in the neonatal intensive care units
      (NICUs) of five German university hospitals between 2009 and 2011. We assessed
      staff work characteristics by surveying 126 NICU nurses and 57 physicians and
      asked 214 parents about their relationships with staff. The outcome variables of
      230 premature infants with birth weights of less than 1500 g were collected over
      a period of 18 months. We used analysis of variance (ANOVA) and regression
      analyses for statistical purposes. RESULTS: We found differences in outcome
      measures between the NICUs, particularly parameters of respiratory support,
      weight gain and length of stay. When we controlled for the NICUs' baseline
      factors, perceptions of the relationship between staff and parents (empathy, p <
      0.001; conversation duration and frequency, p < 0.05; familiarity, p < 0.05) and
      staff work characteristics (workload, p < 0.05) were associated with at least one
      of these outcome measures. CONCLUSION: Staff and parents were discriminators for
      neonatal outcomes through perceptions of work characteristics and the
      relationship between staff and parents, respectively. Respiratory support and
      nutrition measures were particularly sensitive. This research has prompted a
      nationwide, multicentre study of 66 NICUs.

PMID- 25060654
TI  - Perimortem cesarean section for maternal and fetal salvage: concise review and
      protocol.
AB  - Cardiopulmonary arrest is a rare event during pregnancy and labor. Perimortem
      cesarean section has been resorted to as a rare event since ancient times;
      however, greater awareness regarding this procedure within the medical community
      has only emerged in the past few decades. Current recommendations for maternal
      resuscitation include performance of the procedure after five minutes of
      unsuccessful cardiopulmonary resuscitation. If accomplished in a timely manner,
      perimortem cesarean section can result in fetal salvage and is also critical for
      maternal resuscitation. Nevertheless, deficits in knowledge about this procedure
      are common. We have reviewed publications on perimortem cesarean section and
      present the most recent evidence on this topic, as well as recommending our "easy
      to-access protocol" adapted for resuscitation following maternal collapse. 

PMID- 25060655
TI  - Provider collaboration: cohesion, constellations, and shared patients.
AB  - BACKGROUND: There is a natural assumption that quality and efficiency are
      optimized when providers consistently work together and share patients. Diversity
      in composition and recurrence of groups that provide face-to-face care to the
      same patients has not previously been studied. OBJECTIVE: Claims data enable
      identification of the constellation of providers caring for a single patient. To
      indirectly measure teamwork and provider collaboration, we measure recurrence of
      provider constellations and cohesion among providers. DESIGN: Retrospective
      analysis of commercial healthcare claims from a single insurer. PARTICIPANTS:
      Patients with claims for office visits and their outpatient providers. To
      maximize capture of provider panels, the cohort was drawn from the four regions
      with the highest plan coverage. Regional outpatient provider networks were
      constructed with providers as nodes and number of shared patients as links. MAIN
      MEASURES: Measures of cohesion and stability of provider constellations derived
      from the networks of providers to quantify patient sharing. RESULTS: For 10,325
      providers and their 521,145 patients, there were 2,641,933 collaborative provider
      pairs sharing at least one patient. Fifty-four percent only shared a single
      patient, and 19 % shared two. Of 15,449,835 unique collaborative triads, 92 %
      shared one patient, 5 % shared two, and 0.2 % shared ten or more. Patient
      constellations had a median of four providers. Any precise constellation recurred
      rarely-89 % with exactly two providers shared just one patient and only 4 %
      shared over two; 97 % of constellations with exactly three providers shared just
      one patient. Four percent of constellations with 2+ providers were not at all
      cohesive, sharing only the hub patient. In the remaining constellations, a median
      of 93 % of provider pairs shared at least one additional patient beyond the hub
      patient. CONCLUSION: Stunning variability in the constellations of providers
      caring for patients may challenge underlying assumptions about the current state
      of teamwork in healthcare.

PMID- 25060656
TI  - Catalytic asymmetric assembly of C3-monosubstituted chiral carbazolones and
      concise formal synthesis of (-)-aspidofractinine: application of enantioselective
      Pd-catalyzed decarboxylative protonation of carbazolones.
AB  - The first method for the asymmetric synthesis of C3-monosubstituted chiral
      carbazolones, structural motifs common in medicinal chemistry, has been achieved
      using Pd-catalyzed decarboxylative protonation of carbazolones. This methodology
      has been applied to the first catalytic enantioselective formal synthesis of (-)
      aspidofractinine with step economy and simplicity. 

PMID- 25060657
TI  - Association of the 3'UTR FOXO3a polymorphism rs4946936 with an increased risk of
      childhood acute lymphoblastic leukemia in a Chinese population.
AB  - BACKGROUND/AIMS: FOXO3a is an essential tumor suppressor that regulates the
      mechanisms of tumorigenesis and leukemogenesis. FOXO3a polymorphisms have not
      been reported previously associated with an increased risk for childhood acute
      lymphoblastic leukemia (ALL). In this study, the rs4946936 polymorphism located
      in the 3'UTR of FOXO3a was selected to evaluate its relationship with a risk for
      ALL in Chinese children. METHODS: Questionnaires, SNaPshot genotyping, real-time
      PCR, cell transfection and dual luciferase reporter assays were used in this
      study. RESULTS: Parental alcohol consumption and whether the child's house had
      been painted had significantly different distributions among the cases and
      controls. In addition, the C to T mutation was significantly associated with the
      risk for ALL. We determined that FOXO3a expression levels in patients with the CT
      or TT genotype were significantly higher than those of patients with the CC
      genotype. The T allele significantly increased the expression levels in
      luciferase assays and affected the binding affinity of miR-223 to the FOXO3a
      3'UTR. CONCLUSION: Rs4946936 in FOXO3a was highly associated with an increased
      risk of childhood ALL in a Chinese population.

PMID- 25060658
TI  - BCI-FES: could a new rehabilitation device hold fresh promise for stroke
      patients?
AB  - It has been known that stroke constitutes a major source of acquired disability,
      with nearly 800,000 new strokes each year in the USA alone. While advances in
      public and preventative health have helped reduce stroke incidence in high-income
      countries in recent decades, growth of the aging population, increasing stroke
      rates in low- to middle-income countries and medical advances that have reduced
      stroke mortality are all contributing to an increase in stroke survivors
      worldwide. Large numbers of stroke survivors have residual motor deficits. This
      editorial will provide an introduction to a class of new therapies being
      investigated with the aim of improving motor outcomes in stroke patients that
      uses what is known as brain-computer interface technology. 

PMID- 25060659
TI  - A model and nomogram to predict tumor site origin for squamous cell cancer
      confined to cervical lymph nodes.
AB  - BACKGROUND: The current study was conducted to develop a multifactorial
      statistical model to predict the specific head and neck (H&N) tumor site origin
      in cases of squamous cell carcinoma confined to the cervical lymph nodes
      ("unknown primaries"). METHODS: The Surveillance, Epidemiology, and End Results
      (SEER) database was analyzed for patients with an H&N tumor site who were
      diagnosed between 2004 and 2011. The SEER patients were identified according to
      their H&N primary tumor site and clinically positive cervical lymph node levels
      at the time of presentation. The SEER patient data set was randomly divided into
      2 data sets for the purposes of internal split-sample validation. The effects of
      cervical lymph node levels, age, race, and sex on H&N primary tumor site were
      examined using univariate and multivariate analyses. Multivariate logistic
      regression models and an associated set of nomograms were developed based on
      relevant factors to provide probabilities of tumor site origin. RESULTS: Analysis
      of the SEER database identified 20,011 patients with H&N disease with both site
      level and lymph node-level data. Sex, race, age, and lymph node levels were
      associated with primary H&N tumor site (nasopharynx, hypopharynx, oropharynx, and
      larynx) in the multivariate models. Internal validation techniques affirmed the
      accuracy of these models on separate data. CONCLUSIONS: The incorporation of
      epidemiologic and lymph node data into a predictive model has the potential to
      provide valuable guidance to clinicians in the treatment of patients with
      squamous cell carcinoma confined to the cervical lymph nodes.

PMID- 25060660
TI  - Green synthesis of Kocuran-functionalized silver glyconanoparticles for use as
      antibiofilm coatings on silicone urethral catheters.
AB  - Microbial infections due to biofilm formation on medical implants are serious
      complications arising after surgery which can be prevented by using antimicrobial
      coatings on biomaterial surfaces. We developed a simple, rapid and green
      chemistry approach for synthesis of silver glyconanoparticles (AgNPs) using
      Kocuran, an exopolysaccharide produced by Kocuria rosea strain BS-1. Kocuran
      capped AgNPs exhibited a characteristic surface plasmon resonance (SPR) peak
      around 435 nm. They were mono-dispersed, spherical with an average particle size
      of 12 nm. XRD and SAED studies suggested that AgNPs were crystalline in nature.
      AgNPs had a zeta potential of -33.9 mV and were anionic charged. They showed
      colloidal stability at different pH (6 to 10), temperatures (30  degrees C to 100
      degrees C), in NaCl, NaNO3 and BSA solutions. Kocuran-capped AgNPs exhibited
      effective antimicrobial activity against Staphylococcus aureus and Escherichia
      coli and cell death was mainly due to hydroxyl radical induction and depletion of
      NADH. They also inhibited the biofilm development by S. aureus and E. coli and
      confocal scanning laser microscopic images revealed the damage of intact cell
      architecture. In vitro evaluation of Kocuran-capped silver glyconanoparticles on
      human gingival fibroblasts demonstrated good cell proliferation as compared to
      commercial AgNPs suggesting that they are biocompatible and non-toxic in nature.
      This is a first report on Kocuran-functionalized AgNPs exhibiting potential
      antibacterial and antiadhesive properties for use as antimicrobial coatings
      against bacterial adhesion and biofilm formation on silicone urethral catheters. 

PMID- 25060661
TI  - A novel point mutation in the beta1-tubulin gene in asymptomatic
      macrothrombocytopenic Norfolk and Cairn Terriers.
AB  - BACKGROUND: An asymptomatic macrothrombocytopenia, phenotypically similar to
      asymptomatic inherited macrothrombocytopenia in Cavalier King Charles Spaniels,
      was described in a group of Norfolk Terriers (NT) from Northern Italy, and
      isolated cases were also reported in Cairn Terriers (CT). OBJECTIVES: The purpose
      of this work was to evaluate for the presence of a genetic defect in the beta1
      tubulin gene in macrothrombocytopenic NT and CT. METHODS: Samples from 20 healthy
      dogs (13 NT and 7 CT) were collected at different institutions in Italy (n = 8),
      United Kingdom (n = 3), and United States (n = 9). Genomic DNA was harvested from
      EDTA-anticoagulated blood and all coding areas and exon-intron splice sites in
      the gene encoding beta1-tubulin were amplified and sequenced. RESULTS: Twelve
      dogs (9 NT and 3 CT) showed a single nucleotide polymorphism (SNP) in exon 1 at
      nucleotide position 5 (G5A) that would result in the change of an arginine to a
      histidine at amino acid position 2 (R2H). Four dogs (3 NT and one Cairn Terrier)
      were heterozygous for the SNP, and 4 dogs (one Norfolk Terrier and 3 CT) matched
      the normal canine genome. Homozygous dogs for the SNP were macrothrombocytopenic
      with platelet counts ranging from 19,000 to 110,000/MUL. Heterozygous and normal
      dogs had normal platelet counts and morphology. None had the CKCS point mutation.
      CONCLUSIONS: The beta1-tubulin N-terminal amino acids form the nucleotide-binding
      domain and thus this mutation could affect GTP binding enough to influence
      platelet formation in homozygous but not in heterozygous dogs. The presence of
      macrothrombocytopenia only in homozygous affected dogs reveals an association
      between the SNP and the phenotype.

PMID- 25060662
TI  - MicroRNA-144 is a circulating effector of remote ischemic preconditioning.
AB  - Remote ischemic preconditioning (rIPC) induced by cycles of transient limb
      ischemia and reperfusion is a powerful cardioprotective strategy with additional
      pleiotropic effects. However, our understanding of its underlying mediators and
      mechanisms remains incomplete. We examined the role of miR-144 in the
      cardioprotection induced by rIPC. Microarray studies first established that rIPC
      increases, and IR injury decreases miR-144 levels in mouse myocardium, the latter
      being rescued by both rIPC and intravenous administration of miR-144. Going along
      with this systemic treatment with miR-144 increased P-Akt, P-GSK3beta and P
      p44/42 MAPK, decreased p-mTOR level and induced autophagy signaling, and induced
      early and delayed cardioprotection with improved functional recovery and
      reduction in infarct size similar to that achieved by rIPC. Conversely, systemic
      administration of a specific antisense oligonucleotide reduced myocardial levels
      of miR-144 and abrogated cardioprotection by rIPC. We then showed that rIPC
      increases plasma miR-144 levels in mice and humans, but there was no change in
      plasma microparticle (50-400 nM) numbers or their miR-144 content. However, there
      was an almost fourfold increase in miR-144 precursor in the exosome pellet, and a
      significant increase in miR-144 levels in exosome-poor serum which, in turn, was
      associated with increased levels of the miR carriage protein Argonaute-2.
      Systemic release of microRNA 144 plays a pivotal role in the cardioprotection
      induced by rIPC. Future studies should assess the potential for plasma miR-144 as
      a biomarker of the effectiveness of rIPC induced by limb ischemia, and whether
      miR-144 itself may represent a novel therapy to reduce clinical ischemia
      reperfusion injury.

PMID- 25060663
TI  - Evaluation of an antibody avidity index method for detecting recent human
      immunodeficiency virus type 1 infection using an automated chemiluminescence
      immunoassay.
AB  - BACKGROUND: Recent infection testing algorithms (RITAs) are used in public health
      surveillance to estimate the incidence of recently acquired HIV-1 infection.
      OBJECTIVES: Our aims were (i) to evaluate the precision of the VITROS(r) Anti-HIV
      1+2 automated antibody avidity assay for qualitative detection of antibodies to
      HIV 1+2 virus; (ii) to validate the accuracy of an automated guanidine-based
      antibody avidity assay to discriminate between recent and long standing
      infections using the VITROS 3600 platform; (iii) to compare this method with BED
      CEIA assay; and (iv) to evaluate the occurrence of false recent
      misclassifications by the VITROS antibody avidity assay in patients with a CD4
      count <200 cells/MUL and in patients on combination antiretroviral therapy
      (cART). RESULTS: The VITROS(r) antibody avidity assay is highly reproducible. The
      ROC curve analysis of the accuracy of this assay, optimized for sensitivity and
      specificity, had an AI cut off of <=0.51, with sensitivity and specificity values
      of 86.67% (95% CI: 72.51-94.46) and 86.24% (95% CI: 78.00-91.84), respectively.
      The agreement between VITROS antibody avidity and BED-CEIA assays was good.
      Misclassifications of long standing infections as recent infection occurred in
      8.2% of patients with CD4 <200 cell/MUL and 8.7% in patients on combination
      antiretroviral therapy. CONCLUSIONS: The VITROS antibody avidity assay is a
      reliable serological method to detect recent HIV-1 infections and it could be
      incorporated into a RITA to estimate HIV incidence.

PMID- 25060664
TI  - Does cumulative prostate cancer length (CCL) in prostate biopsies improve
      prediction of clinically insignificant cancer at radical prostatectomy in
      patients eligible for active surveillance?
AB  - OBJECTIVES: To evaluate if cumulative prostate cancer length (CCL) on prostate
      needle biopsy divided by the number of biopsy cores (CCL/core) could improve
      prediction of insignificant cancer on radical prostatectomy (RP) in patients with
      prostate cancer eligible for active surveillance (AS). PATIENTS AND METHODS:
      Patients diagnosed with prostate cancer on extended (>=10 cores) biopsy with an
      initial prostate-specific antigen (iPSA) level of <15 ng/mL, clinical stage (cT)
      <= 2a, and highest biopsy Gleason score 3 + 3 = 6 or 3 + 4 = 7 with <3 positive
      cores who underwent RP were included in the study. The CCL/core and presence of
      insignificant cancer (organ-confined, volume <0.5 mL, Gleason score at RP <=6)
      were recorded. pT2 prostate cancer with RP Gleason score <=3 + 4 = 7 and volume
      <0.5 mL were categorised as low-tumour-volume organ-confined disease (LV-OCD).
      RESULTS: In all, 221 patients met the inclusion criteria: the mean age was 59
      years and the median iPSA level was 4.5 ng/mL. The clinical stage was cT1 in 86%
      of patients; biopsy Gleason score was 3 + 3 = 6 in 67% (group 1) and 3 + 4 = 7 in
      33% of patients (group 2). The maximum percentage of biopsy core involvement was
      <50 in 85%; the median CCL/core was 0.15 mm. Insignificant cancer was found in
      27% and LV-OCD in 44% of patients. Group 2 was associated with higher number of
      positive cores, maximum percentage core involvement, total prostate cancer
      length, and CCL/core. Group 1 was more likely to have insignificant cancer (39%)
      or LV-OCD (54%) than group 2 (3% and 23%, respectively). Group 2 had
      significantly higher RP Gleason score and pathological stage. Univariate analysis
      of group 1 showed that the iPSA level, maximum percentage core involvement,
      prostate cancer length, and CCL/core were all significantly associated with
      insignificant cancer and LV-OCD. For group 2, the number of positive cores (1 vs
      2) was also significantly associated with LV-OCD. On multivariate logistic
      regression analysis, maximum percentage core involvement of <50, and number of
      positive cores (1 vs 2) were independent predictors of insignificant cancer in
      group 1; biopsy Gleason score, maximum percentage core involvement of <50 and
      prostate cancer length of <3 mm or CCL/core of <0.2 mm were all independent
      predictors of LV-OCD in the whole population. The maximum percentage of core
      involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm
      were also independent predictors of LV-OCD in group 1 patients. CONCLUSION: In
      patients eligible for AS, a CCL/core of <0.20 mm was significantly associated
      with insignificant cancer and LV-OCD. However, when parameters of cancer burden
      were considered, CCL/core did not independently add any additional value for
      predicting insignificant cancer in patients with biopsy Gleason score 6. The
      CCL/core was an independent predictor of LV-OCD in the whole population and in
      group 1 patients, although the model including prostate cancer length showed
      slightly higher area under the receiver operating characteristic curve.

PMID- 25060665
TI  - Predicting and controlling risks from human exposures to vibration and mechanical
      shock: flag waving and flag weaving.
AB  - At work or in leisure activities, many people are exposed to vibration or
      mechanical shocks associated with risks of injury or disease. This paper
      identifies information that can be used to decide whether there may be a risk
      from exposure to hand-transmitted vibration or whole-body vibration and shock,
      and suggests actions that can control the risks. The complex and time-varying
      nature of human exposures to vibration and shock, the complexity of the different
      disorders and uncertainty as to the mechanisms of injury and the factors
      influencing injury have prevented the definition of dose-response relationships
      well proven by scientific study. It is necessary to wave a flag indicating when
      there is a need to control risks from exposure to vibration and shock while
      scientific enquiry provides understanding needed to weave a better flag. It is
      concluded that quantifying exposure severity is often neither necessary nor
      sufficient to either identify risks or implement measures that control the risks.
      PRACTITIONER SUMMARY: The identification of risks associated with exposure to
      vibration and mechanical shock cannot, and need not, rely solely on the
      quantification of exposure severity. Qualitative methods can provide a sufficient
      indication of the need for control measures, which should not be restricted to
      reducing standardised measures of exposure severity.

PMID- 25060666
TI  - Re-pressurization and rupture of common iliac artery aneurysms.

PMID- 25060667
TI  - On the possibility of lipid-induced regulation of conformation and immunogenicity
      of influenza a virus H1/N1 hemagglutinin as antigen of TI-complexes.
AB  - The tubular immunostimulating complex (TI-complex) consisting of cucumarioside A2
      2, cholesterol and monogalactosyldiacylglycerol (MGDG) from marine macrophytes is
      the perspective antigen delivery system for subunit vaccines. MGDG is a lipid
      matrix for the protein antigen incorporated in the TI-complex. The aim of the
      present work was to study the influence of MGDGs from different macrophytes on
      conformation and immunogenicity of the secreted recombinant uncleaved
      hemagglutinin monomer (HA0S) of influenza A virus H1/N1. Differential scanning
      calorimetry, fluorescence spectroscopy and circular dichroism showed a dependence
      of the conformational changes of HA0S on the microviscosity of MGDG. The most
      viscous MGDG from Zostera marina induced the strongest rearrangements in protein
      conformation. Immunization of mice with HA0S within TI-complexes comprising
      different MGDGs resulted in an approximately 2-fold increase of the levels of
      anti-HA0S antibodies and granulocyte-macrophage colony-stimulating factor (GM
      CSF) compared with those induced by HA0S alone. TI-complexes based on MGDG from
      Z. marina stimulated the maximal production of GM-CSF. However, humoral immune
      response (anti-HA0S antibodies), unlike cell-mediated immune response (GM-CSF),
      did not depend on the physicochemical properties of MGDGs. It is assumed that
      this is due to the different localization and conformational lipid sensitivity of
      the HA0S regions, which are responsible for these types of immune responses.

PMID- 25060668
TI  - Signalling-dependent interactions between the kinase-coupling protein CheW and
      chemoreceptors in living cells.
AB  - Chemical signals sensed on the periplasmic side of bacterial cells by
      transmembrane chemoreceptors are transmitted to the flagellar motors via the
      histidine kinase CheA, which controls the phosphorylation level of the effector
      protein CheY. Chemoreceptor arrays comprise remarkably stable supramolecular
      structures in which thousands of chemoreceptors are networked through
      interactions between their cytoplasmic tips, CheA, and the small coupling protein
      CheW. To explore the conformational changes that occur within this protein
      assembly during signalling, we used in vivo cross-linking methods to detect close
      interactions between the coupling protein CheW and the serine receptor Tsr in
      intact Escherichia coli cells. We identified two signal-sensitive contacts
      between CheW and the cytoplasmic tip of Tsr. Our results suggest that ligand
      binding triggers changes in the receptor that alter its signalling contacts with
      CheW (and/or CheA). 

PMID- 25060669
TI  - Chronic use of NSAIDs and/or statins does not affect PSA or PSA velocity in men
      at high risk for prostate cancer.
AB  - BACKGROUND: PSA and PSA velocity (PSAV, rate of PSA change over time) are
      biomarkers for diagnosis and prognosis of prostate cancer. Men who are at high
      risk for prostate cancer also have associated comorbidities for which they are
      taking NSAIDs and statins for long periods; therefore, it is important to
      understand the effect of these medications on markers used to assess prostate
      cancer risk. METHODS: Using a population of 699 men, multiple linear regressions
      were used to investigate the associations between PSA and concomitant
      medications, and mixed-effects models were used to investigate these associations
      with PSAV. RESULTS: After adjusting for selenium use, age, race, body mass index,
      and pack-years of smoking, aspirin, other NSAIDs, or statins did not demonstrate
      statistically significant associations with PSA (P = 0.79, 0.68, and 0.79,
      respectively) or PSAV (P = 0.23, 0.43, and 0.84, respectively). Results were not
      altered upon stratifying the sample between men who developed prostate cancer
      during the course of the study and those who did not. CONCLUSIONS: Results from
      this study indicate that chronic use of aspirin, other NSAIDs, or statins did not
      affect PSA levels or PSAV in men at high risk for prostate cancer. Larger
      prospective studies designed to investigate these relationships are needed to
      confirm this result. IMPACT: Long-term use of NSAIDs or statins in men at high
      risk for prostate cancer may not interfere with the diagnosis or prognosis of
      this disease, and supports appropriate use of these medications with regard to
      prostate cancer risk.

PMID- 25060670
TI  - Establishing reference intervals for D-dimer to trimesters.
AB  - OBJECTIVE: When D-dimer is used to evaluate suspected venous thromboembolism in
      pregnant patients, the reference interval of common population may cause
      misinterpretation. The present study aims to determine reference intervals of D
      dimer in the three trimesters. METHODS: Four-hundred sixteen pregnant women and
      32 non-pregnant women were enrolled in this cross-sectional study. Reference
      group had comprised 123 pregnant in the first trimester (5-11 week), 164 pregnant
      in the second trimester (13-20 week) and 126 pregnant women in the third
      trimester (25-35 week). D-dimer levels were analyzed via immunoturbidimetric
      assay. RESULTS: If the threshold of 0.50 mg/L for diagnosis of VTE is used, 4.8%
      of pregnant women in the second trimester and 23.8% of pregnant women in the
      third trimester would have D-dimer levels exceeding this cut-off value. Reference
      intervals of D-dimer were determined as 0.11-0.40 mg/L; 0.14-0.75 mg/L and 0.16
      1.3 mg/L in first, second and third trimester, respectively. CONCLUSION: The
      established D-dimer reference intervals for each trimester of pregnancy are
      different from those used in common population. These reference intervals may
      assist clinicians in making accurate clinical decisions. Further studies are
      needed to establish new cut-off values for the D-dimer to rule out VTE in each
      trimester.

PMID- 25060671
TI  - ICH E14 Q&A(R2) document: commentary on the further updated recommendations on
      thorough QT studies.

PMID- 25060672
TI  - Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non-muscle
      invasive bladder cancer.
AB  - OBJECTIVE: Neutrophil-to-lymphocyte ratio (NLR) predicts advanced stage disease
      and decreased survival in patients undergoing radical cystectomy for urothelial
      carcinoma of the bladder. The predictive value of NLR in non-muscle-invasive
      bladder cancer (NMIBC) has not been well studied. We aimed to evaluate whether
      NLR predicted disease recurrence and progression in NMIBC. MATERIALS AND METHODS:
      The medical records of 122 consecutive, newly diagnosed, patients with NMIBC
      treated with transurethral tumor resection, between the years 2003 and 2010, were
      reviewed. Patients with hematological malignancies (n = 4) and without
      preoperative NLR (n = 11) were excluded. Cutoff points for NLR were tested
      separately for recurrence and progression using the standardized cutoff-finder
      algorithm. Univariate and multivariate Cox regression analyses were used to
      evaluate the association between NLR and disease recurrence and progression.
      RESULTS: The study cohort comprised 91 men and 16 women at a median age of 68
      years. The median NLR was 2.85 (interquartile range: 2-3.9). In total, 68
      patients (64%) had an NLR>2.41. Patients with NLR>2.41 were more often men (P =
      0.02) and had T1 category tumors (P = 0.034). Analyzed as a continuous variable,
      higher NLR showed a weak positive association with high tumor grade (R = 0.21, P
      = 0.028). The median follow-up for patients without disease recurrence was 40
      months (interquartile range: 23-51). The estimated 3-year progression-free
      survival rate in patients with an NLR>2.41 was 61%, compared with 84% in patients
      with an NLR<=2.41 (P = 0.004). On multivariate analysis, an NLR>2.41 (hazard
      ratio [HR] = 3.52; 95% CI: 1.33-9.33; P = 0.012) and high-risk tumors compared
      with low-intermediate-risk tumors (HR = 4.83; 95% CI: 1.31-17.77; P = 0.018), as
      defined by the European Organization for Research and Treatment of Cancer risk
      tables, were associated with disease progression. An NLR>2.43 (HR = 1.75; 95% CI:
      1.05-2.92; P = 0.032) and treatment with intravesical instillations (HR = 0.49;
      95% CI: 0.28-0.85; P = 0.011) were associated with disease recurrence on
      multivariate analysis. CONCLUSIONS: NLR is an independent predictor of disease
      progression and recurrence in patients with NMIBC without hematological
      malignancies. Prospective studies are required to validate the role of NLR as a
      prognostic marker in NMIBC.

PMID- 25060673
TI  - An uncommon cause of hypoglycemia: insulin autoimmune syndrome.
AB  - BACKGROUND: Insulin autoimmune syndrome (IAS) is a condition characterized by
      hypoglycemia associated with the presence of autoantibodies to insulin in
      patients who have not been injected with insulin. CASE REPORT: A female patient
      (aged 16 years and 3 months) presented with the complaint of being overweight.
      Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of
      167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to
      be 40 mg/dl, blood ketone was negative and the serum insulin level was determined
      as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia.
      Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The
      daily blood glucose profile revealed postprandial hyperglycemia and reactive
      hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin
      antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie
      diet containing 40% carbohydrate and divided into 6 meals a day was given to the
      patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were
      not observed, but during 2 years of observation, serum levels of insulin and anti
      insulin antibodies remained elevated. CONCLUSION: In all hyperinsulinemic
      hypoglycemia cases, IAS should be considered in the differential diagnosis and
      insulin antibody measurements should be carried out.

PMID- 25060674
TI  - Pharmacological modulation of caspase-8 in thymus-related medical conditions.
AB  - The thymus is a lymphoid organ that governs the development of a diverse T-cell
      repertoire capable of defending against nonself-antigens and avoiding
      autoimmunity. However, the thymus can also succumb to different diseases.
      Hypertrophic diseases, such as thymomas, are typically associated with impairment
      of negative selection, which leads to autoimmune disease, or disruption of
      positive selection, which results in immunodeficiency. Hypotrophic diseases of
      the thymus can manifest during acute infections, cancer, allogeneic bone marrow
      transplantation, or with aging. This condition leads to decreased immune function
      and can be treated by either replacing lost thymic tissue or by preventing thymic
      tissue death. Studies have demonstrated the critical role of caspase-8 in
      regulating apoptosis in the thymus. In this review, we discuss how
      pharmacological activation and inhibition of caspase-8 can be used to treat
      hypertrophic and hypotrophic diseases of the thymus, respectively, to improve its
      function. 

PMID- 25060675
TI  - Sample preparation and biomass determination of SRF model mixture using cryogenic
      milling and the adapted balance method.
AB  - The biogenic fraction of a simple solid recovered fuel (SRF) mixture (80 wt%
      printer paper/20 wt% high density polyethylene) is analyzed with the in-house
      developed adapted balance method (aBM). This fairly new approach is a combination
      of combustion elemental analysis (CHNS) and a data reconciliation algorithm based
      on successive linearisation for evaluation of the analysis results. This method
      shows a great potential as an alternative way to determine the biomass content in
      SRF. However, the employed analytical technique (CHNS elemental analysis)
      restricts the probed sample mass to low amounts in the range of a few hundred
      milligrams. This requires sample comminution to small grain sizes (<200 MUm) to
      generate representative SRF specimen. This is not easily accomplished for certain
      material mixtures (e.g. SRF with rubber content) by conventional means of sample
      size reduction. This paper presents a proof of principle investigation of the
      sample preparation and analysis of an SRF model mixture with the use of cryogenic
      impact milling (final sample comminution) and the adapted balance method
      (determination of biomass content). The so derived sample preparation methodology
      (cutting mills and cryogenic impact milling) shows a better performance in
      accuracy and precision for the determination of the biomass content than one
      solely based on cutting mills. The results for the determination of the biogenic
      fraction are within 1-5% of the data obtained by the reference methods, selective
      dissolution method (SDM) and (14)C-method ((14)C-M).

PMID- 25060676
TI  - Food loss rates at the food retail, influencing factors and reasons as a basis
      for waste prevention measures.
AB  - This paper quantifies food loss rates for fruit & vegetables, dairy products and
      bread & pastry as well as donations to social services. In addition potential
      influencing factors and reasons for food losses are investigated in order to
      provide a basis for the development of waste prevention measures. Detailed data
      from 612 retail outlets all over Austria, which covered the period of one year,
      were analysed and sorting analyses of discarded food were carried out in a small
      sample of retail outlets. Food loss amounts to 1.3% of the sales of dairy
      products, 2.8% for bread & pastry and 4.2% for fruit & vegetables. Returned bread
      amounts to additional 9.7% of the sales of bread & pastry. The food loss rates
      are similar to the results of previous publications. At present, 7% of the food
      loss is donated to social services, 38% of retail outlets do not donate any
      articles at all. Food loss rates are declining with increasing sales areas,
      increasing numbers of purchases per year and increasing sales of the retail
      outlet, but explain only 33% or less of the variation of food loss rates. Large
      differences between retail outlets of comparable structure indicate potential for
      reduction. More than a quarter of discarded food articles did not show any flaws
      besides the expiration of the best before or sell-by date. Waste prevention
      approaches should focus on avoiding returns, transfer of best practices,
      information and education of employees and customers as well as strengthening the
      donation to social services. 

PMID- 25060677
TI  - Molecular ultrastructure of the urothelial surface: insights from a combination
      of various microscopic techniques.
AB  - The urothelium forms the blood-urine barrier, which depends on the complex
      organization of transmembrane proteins, uroplakins, in the apical plasma membrane
      of umbrella cells. Uroplakins compose 16 nm intramembrane particles, which are
      assembled into urothelial plaques. Here we present an integrated survey on the
      molecular ultrastructure of urothelial plaques in normal umbrella cells with
      advanced microscopic techniques. We analyzed the ultrastructure and performed
      measurements of urothelial plaques in the normal mouse urothelium. We used field
      emission scanning electron microscopy (FESEM), atomic force microscopy (AFM),
      transmission electron microscopy (TEM) on immunolabeled ultrathin sections
      (immuno-TEM), and freeze-fracture replicas (FRIL). We performed immunolabeling of
      uroplakins for scanning electron microscopy (immuno-FESEM). All microscopic
      techniques revealed a variability of urothelial plaque diameters ranging from 332
      to 1179 nm. All immunolabeling techniques confirmed the presence of uroplakins in
      urothelial plaques. FRIL showed the association of uroplakins with 16 nm
      intramembrane particles and their organization into plaques. Using different
      microscopic techniques and applied qualitative and quantitative evaluation, new
      insights into the urothelial apical surface molecular ultrastructure have emerged
      and may hopefully provide a timely impulse for many ongoing studies. The
      combination of various microscopic techniques used in this study shows how these
      techniques complement one another. The described advantages and disadvantages of
      each technique should be considered for future studies of molecular and
      structural membrane specializations in other cells and tissues.

PMID- 25060678
TI  - Bone marrow mesenchymal stem cells improve myocardial function in a swine model
      of acute myocardial infarction.
AB  - The aim of the current study was to confirm the effect and elucidate the
      mechanism of bone marrow mesenchymal stem cells (BMSCs) in acute myocardial
      infarction (AMI). AMI was induced in mini-swine by ligating the left anterior
      descending coronary artery, and BMSCs (1x107) were injected via a sterile
      microinjection into the ischemic area. Six months postoperatively,
      electrocardiograph-gated single photon emission computed tomography revealed that
      the myocardial filling defect was reduced and the left ventricular ejection
      fraction was improved in the BMSC group compared with the control group (P<0.05).
      Histopathological examination indicated that, in the BMSC treatment group, the
      percentage of survived myocardial tissue and the vessel density were increased,
      and the percentage of apoptosis was decreased compared with controls (P<0.05).
      Reverse transcription-polymerase chain reaction results indicated that the
      expression levels of multiple inflammatory factors were significantly upregulated
      in the BMSC group compared with levels in the control group (P<0.05). In
      conclusion, the present study demonstrated that BMSC injection significantly
      improved cardiac function and reduced infarct size in six months, indicating that
      this method may be valuable for future study in clinical trials. 

PMID- 25060679
TI  - Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a
      Lynch syndrome family with conserved MLH1 expression tumors.
AB  - Lynch syndrome (LS) is an autosomal dominant cancer-susceptibility disease caused
      by inactivating germline mutations in mismatch repair (MMR) genes. Variants of
      unknown significance (VUS) are often detected in mutational analysis of MMR
      genes. Here we describe a large family fulfilling Amsterdam I criteria carrying
      two rare VUS in the MLH1 gene: c.121G > C (p.D41H) and c.2128A > G (p.N710D).
      Collection of clinico-pathological data, multifactorial analysis, in silico
      predictions, and functional analyses were used to elucidate the clinical
      significance of the identified MLH1 VUS. Only the c.121G > C variant cosegregated
      with LS-associated tumors in the family. Diagnosed colorectal tumors were
      microsatellite unstable although immunohistochemical staining revealed no loss of
      MMR proteins expression. Multifactorial likelihood analysis classified c.2128A >
      G as a non-pathogenic variant and c.121G > C as pathogenic. In vitro functional
      tests revealed impaired MMR activity and diminished expression of c.121G > C.
      Accordingly, the N710 residue is located in the unconserved MLH1 C-terminal
      domain, whereas D41 is highly conserved and located in the ATPase domain. The
      obtained results will enable adequate genetic counseling of c.121G > C and
      c.2128A > G variant carriers and their families. Furthermore, they exemplify how
      cumulative data and comprehensive analyses are mandatory to refine the
      classification of MMR variants.

PMID- 25060680
TI  - Enhanced production of validamycin A in Streptomyces hygroscopicus 5008 by
      engineering validamycin biosynthetic gene cluster.
AB  - Validamycin A (VAL-A) is a widely used antifungal antibiotic for the treatment of
      sheath blight disease of rice and other plants. It can be produced from agro
      industrial by-products by Streptomyces hygroscopicus 5008. To enhance its
      production titer, in this work, the entire val gene cluster was amplified in
      tandem in S. hygroscopicus 5008 by integrating the zouA-mediated DNA
      amplification system into between the two boundaries of val gene cluster,
      resulting in multiple copies (mainly three to five) of the val gene cluster. The
      genetic stability of the amplified copies was confirmed by Southern blot and
      fermentation experiments. In shake flask fermentation, the recombinant strain
      (TC03) led to a 34% enhancement of VAL-A production titer compared to that of the
      wild-type strain, while the accumulation of intermediate validoxylamine A was
      decreased in TC03. Additionally, both the structural gene transcription levels
      and the ValG enzyme activity were significantly increased in TC03. This work
      demonstrated that the amplification of the val gene cluster was an efficient
      strategy to enhance VAL-A production by S. hygroscopicus 5008, and the
      information obtained would be helpful for engineering other interesting
      antibiotic biosynthesis by gene cluster amplification.

PMID- 25060681
TI  - Systemic Listeria monocytogenes infection in a 2-year-old immunocompetent child.
AB  - Central nervous system infection and sepsis are the most frequently observed
      clinical presentations of listeriosis infection; however, they are rare in
      immunocompetent children beyond the neonatal period. In the presented case, we
      described gastrointestinal involvement, subacute meningitis, sinusitis and sepsis
      in a two-year-old previously healthy child with acute infection caused by
      Listeria monocytogenes. We suggest that the infection was probably enhanced by an
      inappropriate corticosteroid treatment at the onset of the disease, while
      immunological testing did not confirm the primary deficiency of cellular
      immunity. 

PMID- 25060682
TI  - Perineal sigmoidopexy utilizing transanal endoscopic microsurgery (TEM) to treat
      full thickness rectal prolapse: a feasibility trial in porcine and human cadaver
      models.
AB  - BACKGROUND: Perineal approaches for rectal prolapse repair have low complication
      rates but high recurrence rates, while abdominal approaches that include
      sigmoidopexy have lower recurrence rates but higher complication rates. To
      optimize both recurrence and complication rates, we developed a novel procedure
      that uses transanal endoscopic microsurgery (TEM) to perform a sigmoidopexy via a
      perineal approach. METHODS: We created a rectal prolapse model in six swine and
      two human cadavers using a previously published technique. The rectum was
      mobilized and eviscerated transanally. After marking the planned point of sigmoid
      transection, the rectum was returned to the peritoneal cavity. A TEM proctoscope
      was inserted transanally alongside the rectum, and the lateral sigmoid colon
      walls were sutured to the sacrum. The sigmoid colon was then transected where
      previously planned, and a primary sigmoid anastomosis was performed. Total
      operative time, sigmoidopexy operative time, and suture security were measured
      and compared to standard rectosigmoidectomy and abdominal sigmoidopexy times.
      RESULTS: No sigmoid colon, iliac vessel, bladder, or ureteral injuries occurred.
      At least two sigmoidopexy sutures were secure on inspection in all animals and
      human cadavers, with increasing success of secure suture placement as experience
      increased. Operative length was similar to traditional abdominal sigmoidopexy.
      CONCLUSIONS: TEM sigmoidopexy is technically feasible. This approach has the
      potential to reduce the recurrence rate associated with perineal approaches
      alone, but further study is needed to confirm this hypothesis.

PMID- 25060683
TI  - The efficacy of topical bupivacaine and triamcinolone acetonide injection in the
      relief of pain after endoscopic submucosal dissection for gastric neoplasia: a
      randomized double-blind, placebo-controlled trial.
AB  - BACKGROUND: Although pain is a common complication of endoscopic submucosal
      dissection (ESD), management strategies are inadequate. The aim of this study was
      to evaluate the efficacy of topical bupivacaine and triamcinolone acetonide for
      abdominal pain relief and as a potential method of pain control after ESD for
      gastric neoplasia. METHODS: In this randomized, double-blind, placebo-controlled
      trial, 111 eligible patients with early gastric neoplasm were randomized into one
      of three groups: bupivacaine (BV) only, bupivacaine with triamcinolone (BV-TA),
      or placebo. The present pain intensity (PPI) score and the Short-Form McGill Pain
      Questionnaire (SF-MPQ) were used to evaluate pain at 0, 6, 12, and 24 h after
      ESD. RESULTS: The mean values for the 6-hour PPI in the BV-TA and BV groups were
      lower than those of the placebo group (1.57 +/- 1.09 and 1.97 +/- 1.09 vs. 2.63
      +/- 0.98, p < 0.001). The 12-hour PPI of the BV-TA group (1.20 +/- 0.83) was the
      lowest among the three groups (p = 0.001). The total 6-hour SF-MPQ score,
      especially in the sensory domain, was higher in the placebo group than in BV and
      BV-TA groups. The 12-hour SF-MPQ score was the lowest in the BV-TA group.
      Multivariate analysis demonstrated that BV-TA injection protocol, fibrosis, and
      size of residual ulcer were independently associated with the PPI score at 6 h.
      CONCLUSION: Bupivacaine after ESD was effective for pain relief at 6 h
      postoperatively. Particularly, topical infiltration of bupivacaine mixed with
      triamcinolone acetonide was helpful for producing a more long-lasting benefit of
      pain relief after gastric ESD.

PMID- 25060684
TI  - On the suitability of Thiel cadavers for natural orifice transluminal endoscopic
      surgery (NOTES): surgical training, feasibility studies, and anatomical
      education.
AB  - BACKGROUND: Surgical training in virtual, animal and cadaver models is essential
      for minimally invasive surgery. Thiel cadavers are suitable for laparoscopy, but
      there are few data about the use of embalmed (Tutsch method) and slightly
      embalmed (Thiel method) cadavers in procedures of Natural Orifice Transluminal
      Endoscopic Surgery (NOTES), which are usually developed and learned on swine
      models and fresh frozen cadavers. The aim of this study was thus to assess the
      use of these cadavers for NOTES approaches. METHODS: The following surgical
      procedures were evaluated: transanal total mesorectal excision (four cadavers:
      one Tutsch, two Thiel, one fresh frozen), transanal ileorectal bypass (five
      cadavers: one Tutsch, three Thiel, one fresh frozen), and transvaginal
      appendectomy (two Tutsch cadaver). RESULTS: The Thiel method ensured tissue
      flexibility and consistency suitable for performing the above surgical procedures
      with good results and without complications, with only a small increase in
      rigidity with respect to fresh specimens. Cadavers embalmed with higher formalin
      concentrations (Tutsch method) were more difficult to use, due to high tissue
      rigidity and resistance of the abdominal wall to pneumoperitoneum, although NOTES
      accesses were possible. CONCLUSIONS: Thiel cadavers are suitable for
      transanal/transrectal and transvaginal NOTES approaches, for training surgical
      residents/specialists and also for surgical research. In minimally invasive
      surgery (and particularly in NOTES), integration between cadaver (fresh frozen
      and/or Thiel) and animal models would represent the gold standard, allowing
      guaranteed knowledge of and respect for human surgical anatomy and correct
      management of surgery on living subjects. NOTES approaches to human cadavers may
      also be proposed for the anatomical education of medical students.

PMID- 25060685
TI  - Transanal endoscopic microsurgery for surgical repair of rectovesical fistula
      following radical prostatectomy.
AB  - BACKGROUND: Rectovesical fistula is a rare complication following prostatectomy,
      associated with significant symptoms such as urinary drainage from anus or
      faecaluria. While several surgical procedures have been described to treat this
      condition, none of them has been accepted as the universal standard. Transanal
      endoscopic microsurgery (TEM) is a well-established endoluminal procedure for
      local excision of rectal tumors. But its application to the repair of
      rectovesical fistula has been almost unknown. METHODS: We performed TEM as a
      surgical repair for refractory rectovesical fistula developing after radical
      prostatectomy in 10 patients. Under the magnified three-dimensional view, through
      the stereoscope, the fistula and the surrounding rectal mucosa were precisely
      resected. The defect and the muscle layer of the rectum were closed by hand-sew
      technique in four layers. RESULTS: Fistula was completely closed in 7 patients,
      who eventually underwent enterostomy closure, while in the other 3 patients the
      fistula recurred. In the three recurrent cases, the fistula was associated with
      wide, tough scar tissue due to previous irradiation, HIFU, or repeated surgical
      repair attempts. CONCLUSIONS: Rectovesical fistulas associated with wide, tough
      scar tissue due to multi-time attempt of surgical repair or any type of energy
      ablation should not be indicated for repair by TEM. However, for simple fistulas
      without tough, fibrotic surroundings, TEM can be indicated as a minimally
      invasive surgical option with very low morbidity, without any incision in healthy
      tissue for approach.

PMID- 25060686
TI  - Which should be the gold standard laparoscopic technique for handling Spigelian
      hernias?
AB  - BACKGROUND: The advantages and disadvantages of both extraperitoneal and intra
      abdominal laparoscopic Spigelian hernia repair are still being discussed. To our
      knowledge, no study has compared both techniques in terms of safety, feasibility,
      and cost-effectiveness. METHOD: Prospective data were collected to compare the
      results of the extraperitoneal approach with the intra-abdominal approach in
      laparoscopic Spigelian hernia repair, between 2000 and 2012 (n = 16). Diagnosis
      was confirmed preoperatively by ultrasonography and/or tomography. RESULTS:
      Spigelian hernias occur mostly in women (69 %), on the left side (56 %) and at a
      median age of 62 (range: 38-83). In our study, the extraperitoneal technique was
      performed in seven patients, while the intra-abdominal approach was indicated in
      nine. No complications, re-admissions, or recurrences were detected in either
      during a mean follow-up of 48 months (range: 18 months-9 years). The statistical
      study showed that there was no difference in either morbidity or the recurrence
      rate between a totally extraperitoneal (TEP) and an intraperitoneal onlay mesh
      (IPOM) repair. The mean duration of an IPOM repair was, though, shorter than that
      of a TEP repair (30 vs. 48 min, P = 0.06). The combined fixation technique (tacks
      + glue) did not modify the results but did reduce the costs, as shown in the cost
      effectiveness study where the intra-abdominal approach was cheaper (1260 vs. 2200
      euros, P < 0.001). CONCLUSION: Laparoscopy seems to be a safe and feasible
      technique whichever the approach chosen, be it intra or extraperitoneal. Our
      experience shows that intra-abdominal laparoscopic Spigelian hernia repair should
      be recommended as the gold standard because of its technical and economic
      advantages. The IPOM procedure with a lightweight titanium-coated mesh fixed
      using a combined technique is a highly effective option for Spigelian hernia
      repair.

PMID- 25060687
TI  - Endoscopic versus open component separation: systematic review and meta-analysis.
AB  - BACKGROUND: The component separation technique (CST) was developed to improve the
      integrity of abdominal wall reconstruction for large, complex hernias. Open CST
      necessitates large subcutaneous skin flaps and, therefore, is associated with
      significant ischemic wound complications. The minimally invasive or endoscopic
      component separation technique (MICST) has been suggested in preliminary studies
      to reduce wound complication rates post-operatively. In this study, we
      systematically reviewed the literature comparing open versus endoscopic component
      separation and performed a meta-analysis of controlled studies. METHODS: A
      comprehensive search of electronic databases was completed. All English,
      randomized controlled trials, non-randomized comparison study, and case series
      were included. All comparison studies included in the meta-analysis were assessed
      independently by two reviewers for methodological quality using the Cochrane Risk
      of Bias tools. RESULTS: 63 primary studies (3,055 patients) were identified; 7
      controlled studies and 56 case series. The total wound complication rate was
      lower for MICST (20.6 %) compared to Open CST (34.6 %). MICST compared to open
      CST was shown to have lower rates of superficial infections (3.5 vs 8.9 %), skin
      dehiscence (5.3 vs 8.2 %), necrosis (2.1 vs 6.8 %), hematoma/seroma formation
      (4.6 vs 7.4 %), fistula tract formation (0.4 vs 1.0 %), fascial dehiscence (0.0
      vs 0.4 %), and mortality (0.4 vs 0.6 %.) The open component CST did have lower
      rates of intra-abdominal abscess formation (3.8 vs 4.6 %) and recurrence rates
      (11.1 vs 15.1 %). The meta-analysis included 7 non-randomized controlled studies
      (387 patients). A similar suggestive overall trend was found favoring MICST,
      although most types of wound complications did not show to significance. MICST
      was associated with a significantly decreased rate of fascial dehiscence and was
      shown to be significantly shorter procedure. CONCLUSION: This systematic review
      and meta-analysis comparing MICST to open CST suggests MICST is associated with
      decreased overall post-operative wound complication rates. Further prospective
      studies are needed to verify these findings.

PMID- 25060688
TI  - Laparoscopic versus open reintervention for anastomotic leakage following
      minimally invasive colorectal surgery.
AB  - PURPOSE: The aim of this study is to evaluate the safety and feasibility of
      laparoscopic reintervention compared with open surgery in patients with
      anastomotic leakage after minimally invasive colorectal surgery. METHODS: Between
      January 2008 and December 2012, 77 patients who required surgical reintervention
      for anastomotic leakage following minimally invasive colorectal surgery were
      included in this study. Data on the patients' demographics, operative management,
      morbidity, hospital stay, and mortality were analyzed for differences based on
      whether they received laparoscopic or open surgery. RESULTS: Sixteen patients
      underwent open surgery following laparoscopy, and 61 patients received
      laparoscopic reintervention following laparoscopy. The conversion rate was 8.2 %
      (5/61). The median total hospital stay following reintervention was significantly
      shorter for laparoscopic surgery (16.0 days, range 9-117 days) than for open
      surgery (35.5 days, range 10-135 days, p < 0.001). The postoperative 30-day
      morbidity rate, including wound dehiscence (25.0 vs 3.3 %, p = 0.015) and intra
      abdominal infection (31.3 vs 6.6 %, p = 0.016), was lower in the laparoscopic
      surgery group than in the open surgery group. The rate of stoma closure was lower
      in the open surgery group than in the laparoscopic surgery group (43.8 vs 80.5 %,
      p < 0.001). There was one in-hospital mortality in the open surgery group.
      CONCLUSIONS: Laparoscopic reintervention for anastomotic leakage following
      minimally invasive colorectal surgery is associated with a shorter hospital stay,
      fewer postoperative complications, and a higher stoma closure rate than open
      surgery. Laparoscopic reintervention for anastomotic leakage is feasible and
      safe.

PMID- 25060689
TI  - Leptin modulates autophagy in human CD4+CD25- conventional T cells.
AB  - OBJECTIVE: In this report we show that the adipocytokine leptin directly
      modulates autophagy in human CD4(+)CD25(-) conventional (Tconv) T cells. RESULTS:
      In vitro treatment with recombinant human leptin determined an inhibition of
      autophagy during T cell receptor (TCR) stimulation, and this phenomenon was dose-
      and time-dependent. The events were secondary to the activation of the mammalian
      target of rapamycin (mTOR)-pathway induced by leptin, as testified by its
      reversion induced by mTOR inhibition with rapamycin. At molecular level these
      phenomena associated with Bcl-2 up-regulation and its interaction with Beclin-1,
      whose complex exerts a negative effect on autophagy. MATERIALS/METHODS: The
      impact of leptin on autophagy of Tconv cells was determined at biochemical level
      by western blotting and by flow cytometry; the interaction between BCL-2 and
      Beclin-1 by co-immunoprecipitation assays. CONCLUSIONS: Our results, suggest that
      in unconditioned, freshly-isolated human Tconv cells, autophagy and proliferation
      are controlled by leptin during TCR-engagement, and that both phenomena occur
      alternatively indicating a balance between these processes during immune
      activation.

PMID- 25060690
TI  - Circulating irisin, omentin-1, and lipoprotein subparticles in adults at higher
      cardiovascular risk.
AB  - OBJECTIVE: Muscle and fat are now recognized as metabolism-regulating endocrine
      organs. However, muscle and adipocyte-derived novel cytokines such as irisin and
      omentin-1 remain understudied in relation to metabolic biomarkers that are
      associated with cardiovascular risk. SUBJECTS AND METHODS: Thirty-nine subjects
      with mean (+/- SD) BMI of 29.2 +/- 5.4 kg/m(2) and either diabetes or two other
      cardiovascular risk factors were enrolled in a 6-month randomized trial of low
      dose ethanol. We examined cross-sectional data at baseline, 3-month, and 6-month
      visits to assess (1) within-person stability of novel cytokines (irisin, omentin
      1, visfatin, resistin, and soluble tumor necrosis factor receptor II) and (2)
      their associations with metabolic parameters, particularly lipoprotein
      subparticle profile. RESULTS: Repeated measures of irisin and omentin-1 were
      highly correlated, with intra-class correlations of 0.84 (95% CI: 0.74, 0.91; P <
      0.001) and 0.81 (0.70, 0.89; P < 0.001), respectively. Irisin was negatively
      correlated with omentin-1 (7.4% irisin decrease per a 1-SD increment in omentin
      1; 95% CI: 0.5%, 13.9%; P = 0.04). In models adjusted for age, sex, and race,
      irisin was negatively associated with HDL cholesterol (7.3% decrease per a
      10mg/dL increment; 1.0%, 13.3%; P = 0.02) and large HDL particles (15.5% decrease
      per a 1-SD or 3.5-MUmol/L increment; 5.2%, 24.7%; P=0.005). Omentin-1 was
      positively associated with mean VLDL size (3.8% increase per a 1-SD increment;
      0.06%, 7.8%; P = 0.05). Adjustment for alcohol intervention, BMI, and other
      cytokines did not materially affect these associations. CONCLUSIONS: Irisin and
      omentin-1 are stable within-person, inversely associated with each other, and
      closely related to lipoprotein profile. These molecules may be promising markers
      for cardiovascular risk.

PMID- 25060691
TI  - Association of GLP-1 secretion with anti-hyperlipidemic effect of ginsenosides in
      high-fat diet fed rats.
AB  - OBJECTIVE: Ginsenosides, major bioactive constituents in Panax ginseng, have been
      shown to exert anti-hyperlipidemia effects. However, the underlying mechanism was
      not well-elucidated due to the low bioavailability of ginsenosides. Glucagon-like
      peptide-1 (GLP-1) was considered to be a critical regulator of energy
      homeostasis. Our previous studies have showed that ginseng total saponins (GTS)
      exhibited antidiabetic effects partly via modulating GLP-1 release. The aim of
      this study was to investigate the potential role of GLP-1 in anti-hyperlipidemia
      effect of GTS in rats fed with high-fat diet. MATERIAL AND METHODS: Male Sprague
      Dawley rats were fed with normal diet (CON) or high-fat diet (HFD) for 4 weeks.
      Then, the HFD rats orally received vehicle (HFD), 150 mg/kg/day (HFD-GL) and 300
      mg/kg/day of GTS (HFD-GH) for another 4 weeks, respectively. RESULTS: Four-week
      GTS treatment significantly ameliorated hyperlipidemia, decreased body fat, liver
      weight and improved insulin resistance. It was found that high-dose GTS treatment
      increased portal GLP-1 level induced by glucose loading, accompanied by increased
      intestinal GLP-1 content, L-cell number and prohormone convertase 3 mRNA
      expression. Data from NCI-H716 cells showed that both GTS and ginsenoside Rb1
      significantly increased GLP-1 secretion as well as proglucagon mRNA level in NCI
      H716 cells supplemented with 10% HFD-rat serum. CONCLUSIONS: Hyperlipidemia and
      insulin resistance were attenuated effectively in response to GTS treatment.
      These improvements may be associated with the increased secretion of GLP-1.

PMID- 25060692
TI  - Shifts in dietary carbohydrate-lipid exposure regulate expression of the non
      alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver
      and HepG2 human liver cells.
AB  - OBJECTIVE: Patatin-like phospholipase domain containing 3 (PNPLA3, adiponutrin)
      has been identified as a modifier of lipid metabolism. To better understand the
      physiological role of PNPLA3/adiponutrin, we have investigated its regulation in
      intact mice and human hepatocytes under various nutritional/metabolic conditions.
      MATERIAL/METHODS: PNPLA3 gene expression was determined by real-time PCR in liver
      of C57BL/6 mice after dietary treatments and in HepG2 cells exposed to various
      nutritional/metabolic stimuli. Intracellular lipid content was determined in
      HepG2 cells after siRNA-mediated knockdown of PNPLA3. RESULTS: In vivo, mice fed
      a high-carbohydrate (HC) liquid diet had elevated hepatic lipid content, and
      PNPLA3 mRNA and protein expression, compared to chow-fed mice. Elevated
      expression was completely abrogated by addition of unsaturated lipid emulsion to
      the HC diet. By contrast, in mice with high-fat diet-induced steatosis, Pnpla3
      expression did not differ compared to low-fat fed mice. In HepG2 cells, Pnpla3
      expression was reversibly suppressed by glucose depletion and increased by
      glucose refeeding, but unchanged by addition of insulin and glucagon. Several
      unsaturated fatty acids each significantly decreased Pnpla3 mRNA, similar to
      lipid emulsion in vivo. However, Pnpla3 knockdown in HepG2 cells did not alter
      total lipid content in high glucose- or oleic acid-treated cells. CONCLUSIONS:
      Our results provide evidence that PNPLA3 expression is an early signal/signature
      of carbohydrate-induced lipogenesis, but its expression is not associated with
      steatosis per se. Under lipogenic conditions due to high-carbohydrate feeding,
      certain unsaturated fatty acids can effectively suppress both lipogenesis and
      PNPLA3 expression, both in vivo and in a hepatocyte cell line.

PMID- 25060693
TI  - Efficacy of topical recombinant human platelet-derived growth factor for
      treatment of diabetic lower-extremity ulcers: Systematic review and meta
      analysis.
AB  - OBJECTIVE: Recombinant human platelet-derived growth factor (rhPDGF) is used
      topically in the treatment of diabetic lower-extremity ulcers. There have been
      few meta-analyses of the efficacy of rhPDGF in this treatment context. The aim of
      this study was to perform an updated systematic review and meta-analysis to
      assess the clinical efficacy of rhPDGF in the treatment of diabetic lower
      extremity ulcers. METHODS: We searched the MEDLINE, Cochrane Library, EMBASE and
      Web of Knowledge databases up to April 30, 2014. Studies were identified and
      selected, and data were extracted by two independent reviewers. The primary
      efficacy outcome was complete healing rate. Adverse events were also assessed.
      The studies were evaluated for quality and publication bias. RESULTS: A total of
      6 randomized controlled trials including 992 patients were selected from 173
      identified studies. The studies compared rhPDGF treatment in the context of
      standard of care (SOC) to placebo or SOC alone. In the absence of study
      heterogeneity, a fixed-effects model was performed, and the combined odds ratio
      (OR) indicated a significantly greater complete healing rate in patients treated
      with rhPDGF compared to placebo or SOC alone. The ORs ranged from 0.58 to 2.77,
      with a combined OR of 1.53 (95% CI = 1.14 to 2.04, p = 0.004). A sensitivity
      analysis (leave-one-out method) indicated good study reliability, and a funnel
      plot with Egger test showed no publication bias. CONCLUSION: These results
      indicate that rhPDGF is efficacious in the treatment of diabetic lower-extremity
      ulcers.

PMID- 25060694
TI  - Liver-specific induction of Abcg5 and Abcg8 stimulates reverse cholesterol
      transport in response to ezetimibe treatment.
AB  - OBJECTIVE: Previous studies have shown ezetimibe treatment results in a 2-6-fold
      increase in reverse cholesterol transport (RCT). However, recent sterol balance
      studies question the role of biliary sterol secretion in RCT, and challenge the
      hypothesis that ezetimibe increases RCT through decreased absorption of biliary
      cholesterol in the intestine. We set out to determine whether ezetimibe may
      increase RCT by mechanisms that are independent of its well-established
      inhibition of intestinal cholesterol absorption. METHODS: C57BL/6J, Npc1l1-KO,
      and/or Abcg8-KO mice were fed a chow diet with or without ezetimibe and fecal
      [(14)C]-neutral and [(14)C]-acidic sterols were measured to examine macrophage-to
      feces RCT. We measured the expression of RCT related genes in the liver and
      jejunum in these mice. To confirm our significant gene expression findings, we
      utilized primary human hepatocytes cultured with or without a glucuronated
      metabolite of ezetimibe. RESULTS: Our studies revealed that treatment with
      ezetimibe was associated with increased expression of hepatic Abcg5 and Abcg8.
      Ezetimibe did not directly affect expression in the liver, but this expression
      was due to the inhibition of intestinal cholesterol absorption. This conclusion
      was supported by the absence of an ABCG5/ABCG8 expression response to treatment
      with an ezetimibe metabolite in primary human hepatocytes. Finally, we found that
      the ezetimibe-dependent stimulation of RCT was attenuated in the absence of
      Abcg8. CONCLUSIONS: Our study is the first to demonstrate ezetimibe treatment
      cooperatively stimulated macrophage-to-feces RCT by indirectly increasing liver
      Abcg5/Abcg8 expression in addition to its known suppression of intestinal
      cholesterol absorption.

PMID- 25060695
TI  - Identification of the minimal replicon and the origin of replication of the
      crenarchaeal plasmid pRN1.
AB  - We have determined the minimal replicon of the crenarchaeal plasmid pRN1. It
      consists of 3097 base pairs amounting to 58% of the genome of pRN1. The minimal
      replicon comprises replication operon orf56/orf904 coding for a transcriptional
      repressor and the replication protein of pRN1. An upstream region of 64 bp that
      contains the promoter of the replication operon is essential as well as 166 bp of
      sequence downstream of the orf904 gene. This region contains a putative
      transcriptional terminator and a 100 nucleotides long stem-loop structure. Only
      the latter structure was shown to be required for replication. In addition
      replication was sustained when the stem-loop was displaced to another part of the
      pRN1 sequence. By mutational analysis we also find that the integrity of the stem
      loop structure is required to maintain the replication of pRN1-derived
      constructs. As similar stem-loop structures are also present in other members of
      the pRN family, we suggest that this conserved structural element could be the
      origin of replication for the pRN plasmids. Further bioinformatic analysis
      revealed that the domain structure of the replication protein and the presence of
      a similar stem-loop structure as the putative replication origin are also found
      in several bacteriophages. 

PMID- 25060696
TI  - RNA polymerase II forms transcription networks in rye and Arabidopsis nuclei and
      its amount increases with endopolyploidy.
AB  - RNA polymerase II (RNAPII) is responsible for the transcription of most
      eukaryotic genes. In mammalian nuclei, RNAPII is mainly localized in relatively
      few distinct transcription factories. In this study--applying super-resolution
      microscopy--it is shown that in plants, inactive (non-phosphorylated) and active
      (phosphorylated) RNAPII modifications compose distinct 'transcription networks'
      within the euchromatin. These reticulate structures sometimes attach to each
      other, but they are absent from heterochromatin and nucleoli. The global RNAPII
      distribution within nuclei is not influenced by interphase chromatin organization
      such as Rabl (rye) versus non-Rabl (Arabidopsis thaliana) orientation.
      Replication of sister chromatids without cell division causes endopolyploidy, a
      phenomenon widespread in plants and animals. Endopolyploidy raises the number of
      gene copies per nucleus. Here, it is shown that the amounts of active and
      inactive RNAPII enzymes in differentiated 2-32C leaf nuclei of A. thaliana
      proportionally increase with rising endopolyploidy. Thus, increasing the
      transcriptional activity of cells and tissues seems to be an important function
      of endopolyploidy.

PMID- 25060697
TI  - The clinical utility of botulinum toxin injections targeted at the motor endplate
      zone in cervical dystonia.
AB  - BACKGROUND AND PURPOSE: Cervical dystonia (CD) patients usually receive repeated
      botulinum neurotoxin (BoNT) injections. The aims of this study were to evaluate
      the feasibility of motor endplate zone (MEZ) detection of relevant cervical
      muscles in CD patients receiving chronic BoNT treatment and to compare the
      treatment effect of half-dosed, endplate-targeted injections to standard BoNT
      injections. METHODS: In study 1, high-density surface electromyography (HD-sEMG)
      was recorded from the sternocleidomastoid (SCM) and splenius capitis (SC) muscles
      in 18 CD patients with ongoing BoNT treatment, by which the location of the MEZ
      was determined. In study 2, nine additional patients with rotational-type CD
      participated in a treatment effect study where they received either half of their
      regular BoNT dose through endplate-targeted injections or their normal BoNT dose
      through standard injections (crossover design). Dystonia severity was recorded
      before and 4 weeks after each treatment session (Toronto Western Spasmodic
      Torticollis Rating Scale severity subscore). RESULTS: In the SCM muscle the MEZ
      was located at the lower border of the superior third part of the muscle, and in
      the SC muscle at half muscle length. Endplate-targeted, half-dosed BoNT injection
      resulted in a similar treatment effect to injecting the full dose in the standard
      technique. CONCLUSIONS: Half-dosed, endplate-targeted BoNT injections lead to a
      similar treatment effect to the standard BoNT injection protocol. MEZ detection
      confronts the clinician with some technical challenges, such as the ability of
      accurate and technically optimal placement of the electrode grid and correct
      interpretation of the HD-sEMG signal.

PMID- 25060698
TI  - Gonorrhoea of the sigmoid neovagina in a male-to-female transgender.
AB  - A 33-year-old male-to-female transgender consulted our outpatient clinic with
      perneovaginal bleeding during and following coitus. Four years before, she
      underwent a total laparoscopic sigmoid neovaginoplasty. Physical, histological
      and endoscopic examination revealed neither focus of active bleeding nor signs of
      active inflammation. A polymerase chain reaction test performed on a neovaginal
      swab showed gonococcal infection. Treatment consisted of 500 mg intramuscular
      ceftriaxone. Three weeks later, our patient reported resolution of symptoms,
      consistent with eradication of the infection demonstrated by a follow-up
      neovaginal swab polymerase chain reaction. To our knowledge, this is the first
      case report of gonococcal infection of the sigmoid neovagina. 

PMID- 25060699
TI  - Prevalence of suicidal ideation and associated factors among HIV-positive MSM in
      Anhui, China.
AB  - The aim of this study was to investigate the prevalence and factors associated
      with suicidal ideation among HIV-positive men who have sex with men (MSM) in
      Anhui, China. A cross-sectional study was conducted to recruit HIV-positive MSM
      in Anhui, China. A total of 184 HIV-positive MSM gave informed consent and
      completed the interview. Correlates of suicidal ideation were assessed using
      multivariable logistic regression. Fifty-seven (31%) of HIV-positive MSM had
      suicidal ideations within six months before the interview. Multivariable analyses
      showed that learning of their HIV status in the past 12 months (adjusted odds
      ratio (AOR) = 3.4, 95% CI = 1.6-7.3), perceived HIV stigma (AOR = 2.4, 95% CI =
      1.1-5.2), depression symptoms (AOR = 2.6, 95% CI = 1.1-5.9) and anxiety symptoms
      (AOR = 2.7, 95% CI = 1.2-6.1) were significantly associated with the suicidal
      ideation among HIV-positive MSM. The results indicated that suicidal ideation was
      common among HIV-positive MSM in Anhui, China. There is an urgent need to
      establish psychological counselling services among HIV-positive MSM in China.
      Targeting of these potential risk factors could be an effective approach to
      reduce the suicide risk among this high-risk subgroup by the implementation of
      early intervention measurements. 

PMID- 25060700
TI  - Time trends in municipal distribution patterns of cancer mortality in Spain.
AB  - BACKGROUND: New disease mapping techniques widely used in small-area studies
      enable disease distribution patterns to be identified and have become extremely
      popular in the field of public health. This paper reports on trends in the
      geographical mortality patterns of the most frequent cancers in Spain, over a
      period of 20 years. METHODS: We studied the municipal spatial pattern of stomach,
      colorectal, lung, breast, prostate and urinary bladder cancer mortality in Spain
      across four quinquennia, spanning the period 1989-2008. Case data were broken
      down by town (8073 municipalities), period and sex. Expected cases for each town
      were calculated using reference rates for each five-year period. For map plotting
      purposes, smoothed municipal relative risks were calculated using the conditional
      autoregressive model proposed by Besag, York and Mollie, with independent data
      for each quinquennium. We evaluated the presence of spatial patterns in maps on
      the basis of models, calculating the variance in relative risk corresponding to
      the structured spatial component and the unstructured component, as well as the
      proportion of variance explained by the structured spatial component. RESULTS:
      The mortality patterns observed for stomach, colorectal and lung cancer were
      maintained over the 20 years covered by the study. Prostate cancer and the
      tumours studied in women showed no defined spatial pattern, with the single
      exception of stomach cancer. The trend in spatial fractional variance indicated
      the possibility of a change in the spatial pattern in breast, bladder and
      colorectal cancer in women during the last five-year period. The paper goes on to
      discuss ways in which spatio-temporal data are depicted in the case of cancer,
      and review the risk factors that may possibly influence the respective tumours'
      spatial patterns. CONCLUSION: In men, the marked geographical patterns of
      stomach, colorectal, lung and bladder cancer remained stable over time. Breast,
      colorectal and bladder cancer in women show signs of the possible appearance of a
      spatial pattern in Spain and should therefore be monitored.

PMID- 25060701
TI  - LeA(H)Rning self-control.
AB  - The aryl hydrocarbon receptor (AhR) is an important regulator of the immune
      response. A report by Puccetti and coworkers describes a regulatory pathway by
      which L-kynurenine (L-Kyn) produced by tryptophan 2,3-dioxygenase 2 (TDO2)
      activates AhR in cells of the innate immune system to limit endotoxin-triggered
      inflammation through a mechanism that involves the non-enzymatic anti
      inflammatory activities of indoleamine 2,3-dioxygenase 1 (IDO1). 

PMID- 25060702
TI  - A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
AB  - Thyroid transcription factor-1 (TTF-1, also known as NKX2-1) is a tissue-specific
      transcription factor in lung epithelial cells. Although TTF-1 inhibits the
      epithelial-to-mesenchymal transition induced by transforming growth factor-beta
      (TGF-beta) in lung adenocarcinoma cells, the mechanism through which TTF-1
      inhibits the functions of TGF-beta is unknown. Here we show that TTF-1 disrupts
      the nuclear Smad3-Smad4 complex without affecting the nuclear localization of
      phospho-Smad3. Genome-wide analysis by chromatin immunoprecipitation followed by
      sequencing revealed that TTF-1 colocalizes with Smad3 on chromatin and alters
      Smad3-binding patterns throughout the genome, while TTF-1 generally inhibits
      Smad4 binding to chromatin. Moreover, Smad3 binds to chromatin together with TTF
      1, but not with Smad4, at some Smad3-binding regions when TGF-beta signaling is
      absent, and knockdown of Smad4 expression does not attenuate Smad3 binding in
      these regions. Thus, TTF-1 may compete with Smad4 for interaction with Smad3, and
      in the presence of TTF-1, Smad3 regulates the transcription of certain genes
      independently of Smad4. These findings provide a new model of regulation of TGF
      beta-Smad signaling by TTF-1. 

PMID- 25060703
TI  - Relaxing the independent censoring assumption in the Cox proportional hazards
      model using multiple imputation.
AB  - The Cox proportional hazards model is frequently used in medical statistics. The
      standard methods for fitting this model rely on the assumption of independent
      censoring. Although this is sometimes plausible, we often wish to explore how
      robust our inferences are as this untestable assumption is relaxed. We describe
      how this can be carried out in a way that makes the assumptions accessible to all
      those involved in a research project. Estimation proceeds via multiple
      imputation, where censored failure times are imputed under user-specified
      departures from independent censoring. A novel aspect of our method is the use of
      bootstrapping to generate proper imputations from the Cox model. We illustrate
      our approach using data from an HIV-prevention trial and discuss how it can be
      readily adapted and applied in other settings.

PMID- 25060704
TI  - N-heterocyclic carbene coordinated neutral and cationic heavier
      cyclopropylidenes.
AB  - Cyclopropylidene is a transient intermediate of the allene-propyne-cyclopropene
      isomerization. The incorporation of heavier Group 14 elements into the
      cyclopropylidene scaffold has to date been restricted to the formal replacement
      of the carbenic carbon atom by a base-coordinated silicon(II) center. Herein we
      report the synthesis and characterization of NHC-coordinated heavier
      cyclopropylidenes (Si2GeR3X, and Si3R3Br; X=Cl, Mes; R=Tip=2,4,6-iPr3C6H2) in
      which the three-membered ring is exclusively formed by silicon and germanium. In
      case of the chloro-substituted Si2Ge-cyclopropylidene, a stable heavier cycloprop
      1-yl-2-ylidene cation is obtained by NHC-induced chloride dissociation.

PMID- 25060706
TI  - Addition of docosahexaenoic acid, but not arachidonic acid, activates glutathione
      and thioredoxin antioxidant systems in murine hippocampal HT22 cells: potential
      implications in neuroprotection.
AB  - Docosahexaenoic acid (DHA, 22:6n-3) is a major constituent of nerve cell membrane
      phospholipids. Besides a role in membrane architecture, DHA is a pleiotropic
      molecule involved in multiple facets of neuronal biology and also in
      neuroprotection. We show here that supplementation with DHA (but not arachidonic
      acid) to mouse hippocampal HT22 cells modulates the expression of genes encoding
      for antioxidant proteins associated with thioredoxin/peroxiredoxin and
      glutathione/glutaredoxin systems. Thus, within the thioredoxin system, DHA
      increased Txn1-2, Trxrd1-2, Prdx3, and Srxn1 gene expression. Paralleling these
      changes, DHA increased thioredoxin reductase activity, the main enzyme involved
      in thioredoxin regeneration. For the glutathione system, the most important
      change triggered by DHA was the upregulation of Gpx4 gene, encoding for the
      nuclear, cytosolic and mitochondrial isoforms of phospholipid-hydroperoxide
      glutathione peroxidase (PH-GPx/GPx4, the main enzyme protecting cell membranes
      against lipid peroxidation), which was followed by a significant increase in
      total glutathione peroxidase and GPx4 activities. Noticeably, DHA also
      upregulated a new Gpx4 splicing variant that retained part of the first intronic
      region. Finally, we demonstrate that DHA treatment, under the same time course,
      protects HT22 cells from the oxitoxic exposure to amyloid beta (Abeta25-35 )
      peptide. Altogether, our data pinpoint to a role of DHA as Indirect Antioxidant
      that modulates neuronal defences in neuroprotection. DHA improves the antioxidant
      capacity of cultured hippocampal HT22 cells. We propose that DHA supplementation
      induces the remodelling of membrane phospholipids, and also triggers a
      transcriptional program to increase the expression of members of the glutathione
      and thioredoxin systems. We postulate that this transcriptional effect is
      mediated by a signal arising from non-enzymatic oxidation of DHA. 

PMID- 25060705
TI  - Histone methylation and V(D)J recombination.
AB  - V(D)J recombination is the process by which the diversity of antigen receptor
      genes is generated and is also indispensable for lymphocyte development. This
      recombination event occurs in a cell lineage- and stage-specific manner, and is
      carefully controlled by chromatin structure and ordered histone modifications.
      The recombinationally active V(D)J loci are associated with hypermethylation at
      lysine4 of histone H3 and hyperacetylation of histones H3/H4. The recombination
      activating gene 1 (RAG1) and RAG2 complex initiates recombination by introducing
      double-strand DNA breaks at recombination signal sequences (RSS) adjacent to each
      coding sequence. To be recognized by the RAG complex, RSS sites must be within an
      open chromatin context. In addition, the RAG complex specifically recognizes
      hypermethylated H3K4 through its plant homeodomain (PHD) finger in the RAG2 C
      terminus, which stimulates RAG catalytic activity via that interaction. In this
      review, we describe how histone methylation controls V(D)J recombination and
      discuss its potential role in lymphoid malignancy by mistargeting the RAG
      complex. 

PMID- 25060707
TI  - HMGN2, a new anti-tumor effector molecule of CD8+ T cells.
AB  - BACKGROUND: Cytolytic T lymphocytes (CTL) and natural killer (NK) cells have been
      implicated as important cells in antitumor responses. Our previous research has
      shown that high mobility group nucleosomal-binding domain 2 (HMGN2) could be
      released by IL-2 and PHA stimulated peripheral blood mononuclear cells (PBMCs)
      and also induced tumor cells apoptosis at low doses. In this study, we isolated
      and cultured PBMCs and CD8+ T cells to analyze the expression and antitumor
      effects of HMGN2. METHODS: PBMCs from healthy donors were isolated using Human
      Lymphocyte Separation tube. CD8+ T cells were separated from the PBMCs using
      MoFlo XDP high-speed flow cytometry sorter. Activation of PBMCs and CD8+ T cells
      were achieved by stimulating with Phytohemagglutinin (PHA) or tumor antigen. In
      addition, the methods of ELISA, intracellular staining, and fluorescence-labeling
      assays were used. RESULTS: PHA induced PBMCs to release high levels of HMGN2, and
      CD8+ T cells was the major cell population in PBMCs that release HMGN2 after PHA
      activation. Tumor antigen-activated CD8+ T cells also released high levels of
      HMGN2. Supernatants of tumor antigen-activated CD8+ T cells were able to kill
      tumor cells in a dose-dependent manner. This antitumor effect could be
      significantly blocked by using an anti-HMGN2 antibody. Fluorescence-labeling
      assays showed that the supernatant proteins of activated CD8+ T cells could be
      transported into tumor cells, and the transport visibly decreased after HMGN2 was
      depleted by anti-HMGN2 antibody. CONCLUSIONS: These results suggest that HMGN2 is
      an anti-tumor effector molecule of CD8+ T cells.

PMID- 25060708
TI  - Nutritional status modulates box C/D snoRNP biogenesis by regulated subcellular
      relocalization of the R2TP complex.
AB  - BACKGROUND: Box C/D snoRNPs, which are typically composed of box C/D snoRNA and
      the four core protein components Nop1, Nop56, Nop58, and Snu13, play an essential
      role in the modification and processing of pre-ribosomal RNA. The highly
      conserved R2TP complex, comprising the proteins Rvb1, Rvb2, Tah1, and Pih1, has
      been shown to be required for box C/D snoRNP biogenesis and assembly; however,
      the molecular basis of R2TP chaperone-like activity is not yet known. RESULTS:
      Here, we describe an unexpected finding in which the activity of the R2TP complex
      is required for Nop58 protein stability and is controlled by the dynamic
      subcellular redistribution of the complex in response to growth conditions and
      nutrient availability. In growing cells, the complex localizes to the nucleus and
      interacts with box C/D snoRNPs. This interaction is significantly reduced in
      poorly growing cells as R2TP predominantly relocalizes to the cytoplasm. The R2TP
      snoRNP interaction is mainly mediated by Pih1. CONCLUSIONS: The R2TP complex
      exerts a novel regulation on box C/D snoRNP biogenesis that affects their
      assembly and consequently pre-rRNA maturation in response to different growth
      conditions.

PMID- 25060709
TI  - Fibroblast sources: Where can we get them?
AB  - Fibroblasts are cells widely used in cell culture, both for transient primary
      cell culture or permanent as transformed cell lines. Lately, fibroblasts become
      cell sources for use in disease modeling after cell reprogramming because it is
      easily accessible in the body. Fibroblasts in patients will maintain all genetic
      background during reprogramming into induced pluripotent stem cells. In spite of
      their large use, fibroblasts are obtained after an invasive procedure, a
      superficial punch skin biopsy, collected under patient's local anesthesia. Taking
      into consideration the minimum patient's discomfort during and after the biopsy
      procedure, as well as the aesthetics aspect, it is essential to reflect on the
      best site of the body for the biopsy procedure combined with the success of
      getting robust fibroblast cultures in the lab. For this purpose, we compared the
      efficiency of four biopsy sites of the body (skin from eyelid, back of the ear,
      abdominal cesarean scar and groin). Cell proliferation assays and viability after
      cryopreservation were measured. Our results revealed that scar tissue provided
      fibroblasts with higher proliferative rates. Also, fibroblasts from scar tissues
      presented a higher viability after the thawing process. 

PMID- 25060710
TI  - Low blood cell counts in wild Japanese monkeys after the Fukushima Daiichi
      nuclear disaster.
AB  - In April 2012 we carried out a 1-year hematological study on a population of wild
      Japanese monkeys inhabiting the forest area of Fukushima City. This area is
      located 70 km from the Fukushima Daiichi Nuclear Power Plant (NPP), which
      released a large amount of radioactive material into the environment following
      the Great East Japan Earthquake of 2011. For comparison, we examined monkeys
      inhabiting the Shimokita Peninsula in Aomori Prefecture, located approximately
      400 km from the NPP. Total muscle cesium concentration in Fukushima monkeys was
      in the range of 78-1778 Bq/kg, whereas the level of cesium was below the
      detection limit in all Shimokita monkeys. Compared with Shimokita monkeys,
      Fukushima monkeys had significantly low white and red blood cell counts,
      hemoglobin, and hematocrit, and the white blood cell count in immature monkeys
      showed a significant negative correlation with muscle cesium concentration. These
      results suggest that the exposure to some form of radioactive material
      contributed to hematological changes in Fukushima monkeys.

PMID- 25060713
TI  - The fundamentals of fetal MR imaging: Part 1.
AB  - Congenital malformations detected in any fetal system using ultrasound may be
      further evaluated with magnetic resonance imaging (MRI) to improve counseling, to
      plan deliveries appropriately, and sometimes to enable fetal interventions. In
      this first half of a 2-part review, the history and safety factors regarding
      fetal MRI, as well as the practical aspects of image acquisition, are discussed.
      In addition, as central nervous system anomalies are most commonly and best
      evaluated using fetal MRI, challenging central nervous system anomalies, such as
      fetal ventriculomegaly, posterior anomalies, and neural tube defects, detected
      using prenatal ultrasound are also reviewed with a focus on the fundamental
      implications of these diagnoses. 

PMID- 25060711
TI  - Nanosecond pulsed electric fields (nsPEFs) regulate phenotypes of chondrocytes
      through Wnt/beta-catenin signaling pathway.
AB  - Nanosecond pulsed electric fields (nsPEFs) characterized by high voltage, low
      energy and non-thermal effects, have been broadly investigated as a potential
      tumor therapy; however, little is known about their effects on somatic cells. In
      this current study, we evaluated effects of nsPEFs on the phenotype of
      chondrocytes (morphology, glycosaminoglycan (GAG) content, proliferation and gene
      expression) and explored the mechanisms involved. Our results demonstrated that
      exposing chondrocytes to nsPEFs led to enhanced proliferation and
      dedifferentiation, evidenced by the upregulated gene expression of collagen type
      I (COL I) and downregulated gene expression of Sox9, collagen type II (COL II)
      and aggrecan (AGG) with activation of the wnt/beta-catenin signaling pathway.
      Inhibition of the wnt/beta-catenin pathway partially blocked these effects. Thus
      we concluded that nsPEFs induce dedifferentiation of chondrocytes partially
      through transient activation of the wnt/beta-catenin signaling pathway. 

PMID- 25060714
TI  - Optimisation of ultrasound-assisted extraction of natural antioxidants from
      mustard seed cultivars.
AB  - BACKGROUND: Modified mustard varieties can produce edible oil with reduced
      amounts of erucic acid and glucosinolates and enhanced antioxidant potential.
      Therefore, this work focused on the optimisation of the ultrasound-assisted
      extraction of compounds with high antioxidant capacity from three white mustard
      seed cultivars using response surface methodology. RESULTS: The predicted optimum
      solvent polarity (57.2, 56.5 and 57.6) and ultrasound power-to-sonication time
      ratio (4.5, 4.8 and 4.3 W min(-1)) resulted in antioxidant capacities determined
      by the ferric-reducing antioxidant power (FRAP) assay [54.37, 65.75 and 68.55
      mmol Trolox equivalent (TE) kg(-1)] and the 2,2'-diphenyl-1-picrylhydrazyl (DPPH)
      method (141.65, 175.26 and 185.10 mmol TE kg(-1)) and total phenolics content
      (23.70, 27.16 and 11.29 mg sinapic acid g(-1)) for extracts obtained from one
      traditional and two modified mustard seed varieties. The highest FRAP and DPPH
      values (69.51 and 197.73 mmol TE kg(-1)) revealed 50% methanolic extract prepared
      from modified mustard seed cultivar without erucic acid and glucosinolates
      treated with ultrasound for 30 min (ultrasound power/ultrasound time = 4 W min(
      1)). CONCLUSION: Ultrasound-assisted extraction was found to be a more rapid,
      convenient and appropriate extraction method with higher yield of antioxidants,
      shorter time and lower solvent consumption in comparison to conventional
      extraction.

PMID- 25060715
TI  - Association of promoter polymorphism -765G>C in the PTGS2 gene with malignant
      melanoma in Italian patients and its correlation to gene expression in dermal
      fibroblasts.
AB  - Prostaglandins, especially prostaglandin E synthetase (PGE2), influence
      carcinogenesis by promoting cell proliferation, inhibiting apoptosis, stimulating
      angiogenesis and mediating immune suppression. Cyclooxygenase-2, coded by the
      PTGS2 gene, is the key enzyme in the production of prostaglandins. In melanoma,
      Cox-2 is over expressed in primary malignant melanoma (MM) and in their
      corresponding metastases. Polymorphisms in the promoter region of PTGS2 gene can
      modulate gene expression and could modify individual susceptibility to MM. Two
      hundred and forty melanoma patients and 342 controls were genotyped for
      polymorphisms -765G>C (rs20417) and -1195A>G (rs689466). Allele -765C frequency
      was significantly higher in melanoma patients. No allele frequency differences
      for -1195A>G polymorphism were observed. Haplotype analysis revealed that the
      haplotypes carrying the minor alleles were associated to a higher risk of
      melanoma (P = 0.02). Expression analysis showed that allele -765C is associated
      to a higher gene expression and could represent a risk allele by affecting the
      functionality of the promoter. 

PMID- 25060716
TI  - Is there an association between sonographically determined occipito-transverse
      position in the second stage of labor and operative delivery?
AB  - OBJECTIVE: To evaluate if ultrasound-determined occipito-transverse position
      early in the second stage of labor is associated with operative delivery. DESIGN:
      Retrospective review of two prospective cohort studies. SETTING: An Australian
      tertiary referral hospital. POPULATION: Women with term, cephalic singleton
      pregnancies. METHODS: Retrospective analysis of data from two prospective
      studies. Logistic regression was undertaken to assess the independent
      contribution of the occipito-transverse position to operative delivery. MAIN
      OUTCOME MEASURE: Operative delivery (cesarean section, forceps or vacuum
      extraction). RESULTS: Among 422 women included, the occipito-transverse position
      was present in 80, occipito-anterior in 303 and the occipito-posterior in 39.
      Compared with occipito-anterior, the adjusted odds ratio for operative delivery
      was 2.1 (95% confidence interval 1.2-3.8, p = 0.02) for the occipito-transverse
      position, and 7.4 (95% confidence interval 3.2-17) for the occipito-posterior
      position. Factors that independently predicted operative delivery were
      nulliparity, abnormal second stage cardiotocography, maternal place of birth and
      epidural analgesia. The length of second stage of labor was longer for the
      occipito-transverse group than for the occipito-anterior group (median 2 h 7 min
      vs. 1 h 36 min, p = 0.003). CONCLUSION: The occipito-transverse position early in
      the second stage of labor was associated with an increased operative delivery
      rate.

PMID- 25060717
TI  - Thoracoscopic radiofrequency ablation for lone atrial fibrillation: box-lesion
      technique.
AB  - BACKGROUND: We report the feasibility and outcomes of box-lesion ablation
      technique to treat stand-alone atrial fibrillation (AF). METHODS: There were 41
      patients with a mean age of 57.6 +/- 8.0 years who underwent bilateral totally
      thoracoscopic ablation of symptomatic paroxysmal AF (n = 24; 58.5%), persistent
      AF (n = 9; 22.0%), or long-standing persistent AF (n = 8; 19.5%). The box-lesion
      procedure included bilateral pulmonary vein and left atrial posterior wall
      ablation using irrigated bipolar radiofrequency with documentation of conduction
      block. RESULTS: There were no intra- or perioperative ablation-related
      complications. There was no operative mortality, no myocardial infarction, and no
      stroke. Skin-to-skin procedure time was 119.5 +/- 23.7 minutes and the
      postoperative average length of stay was 7.4 +/- 2.5 days. At discharge, 38
      patients (93%) were in sinus rhythm. Median follow-up time was 641 days (ranges,
      185-1636 days). At six months postsurgery, 31 patients of 41 (76%) were free from
      AF without the need of antiarrhythmic drugs. One-year success rate was 73% (off
      antiarrhythmic drugs). Eight patients (19.5%) underwent catheter reablation.
      Thirty-six patients (90%) were in sinus rhythm at six months after the last
      performed ablation (surgical ablation or catheter reablation). At 12 months
      follow-up, 61% patients discontinued oral anticoagulant therapy. CONCLUSION: The
      thoracoscopic box-lesion ablation procedure is a safe, effective, and minimally
      invasive method for the treatment of isolated (lone) AF. This procedure provided
      excellent short-term freedom from AF.

PMID- 25060718
TI  - Neurological complications of bariatric surgery.
AB  - Obesity is reaching pandemic proportions, and the number of bariatric surgeries
      is increasing. Neurological complications of bariatric procedures are more and
      more frequently reported and physicians need to recognize and be able to manage
      them. Neurological complications may result from mechanical or inflammatory
      mechanisms, but mainly from nutritional deficiencies. Vitamin B12, folate,
      thiamine, vitamin D, and vitamin E are the most frequent deficiencies. Different
      patterns of complications can be observed that may differ from time to
      presentation. At an early stage, immediate peripherical nerve injury, Wernicke's
      encephalopathy, and polyradiculoneuropathy are the most frequent. Late
      complications may appear after years and include optic neuropathy, myelopathy,
      peripherical neuropathy, and myopathy. Bariatric surgery patients should benefit
      from careful nutritional follow-up with routine monitoring of micronutrients at 6
      weeks and 3, 6, and 12 months post-op and then annually after surgery, and
      multivitamin supplementation for life.

PMID- 25060719
TI  - Measurement properties of asthma-specific quality-of-life measures: protocol for
      a systematic review.
AB  - BACKGROUND: Asthma is a frequent chronic inflammatory disease of the airways, and
      the assessment of health-related quality of life (HrQoL) is important in both
      research and routine care. Various asthma-specific measures of HrQoL exist but
      there is uncertainty which measures are best suited for use in research and
      routine care. Therefore, the aim of the proposed research is a comprehensive
      systematic assessment of the measurement properties of the existing measures that
      were developed to measure asthma-specific quality of life. METHODS/DESIGN: This
      study is a systematic review of the measurement properties of asthma-specific
      measures of health-related quality of life. PubMed and Embase will be searched
      using a selection of relevant search terms. Eligible studies will be primary
      empirical studies evaluating, describing or comparing measurement properties of
      asthma-specific HRQL tools. Eligibility assessment and data abstraction will be
      performed independently by two reviewers. Evidence tables will be generated for
      study characteristics, instrument characteristics, measurement properties and
      interpretability. The quality of the measurement properties will be assessed
      using predefined criteria. Methodological quality of studies will be assessed
      using the COnsensus-based Standards for the selection of health Measurement
      INstruments (COSMIN) checklist. A best evidence synthesis will be undertaken if
      more than one study have investigated a particular measurement property.
      DISCUSSION: The proposed systematic review will produce a comprehensive
      assessment of measurement properties of existing measures of asthma-specific
      health-related quality of life. We also aim to derive recommendations in order to
      help researchers and practitioners alike in the choice of instrument. TRIAL
      REGISTRATION: PROSPERO registration number: CRD42014010491.

PMID- 25060720
TI  - Orally delivered microencapsulated probiotic formulation favorably impacts polyp
      formation in APC (Min/+) model of intestinal carcinogenesis.
AB  - The development of intestinal polyps in an orthotopic colorectal mouse model,
      receiving a probiotic yogurt formulation containing microencapsulated live
      Lactobacillus acidophilus cells was investigated. The expression of various
      immunohistochemical markers namely CD8, Mac-1, Ki-67, and cleaved caspase-3, was
      evaluated. Results suggest that the probiotic formulation decreases overall
      intestinal inflammation. Mice receiving the probiotic formulation were found to
      develop almost two-fold fewer tumors in the small intestines. In the large
      intestine, however, there was no significant difference observed among polyp
      numbers. The formulation appears to have potential application in the prevention
      of various GI pathological conditions. 

PMID- 25060721
TI  - Effect of oxygenated polyethylene glycol decorated hemoglobin on microvascular
      diameter and functional capillary density in the transgenic mouse model of sickle
      cell anemia.
AB  - Malemide polyethylene glycol-conjugated Hb (MP4OX, Sangart Inc.), a high-affinity
      low-concentration acellular hemoglobin (P50 = 5 mmHg, 4.3 g/dl) solution, has
      been shown to optimize microvascular perfusion and target oxygen delivery to
      anoxic tissue. Microvascular perfusion during an acute hypoxic challenge in a
      transgenic anemic sickle cell disease mouse model was studied with MP4OX and
      saline. Arterioles were dilated in both groups. Functional capillary density
      (FCD) was maintained at a higher level with MP4OX. In conclusion, MP4OX treatment
      reduced the hypoxia-mediated decline in FCD, an effect in part due to higher
      arterial pressure resulting in increased microvascular perfusion pressures.

PMID- 25060722
TI  - Heart failure-induced diaphragm myopathy.
AB  - BACKGROUND: Intracellular signaling pathways involved in skeletal myosin heavy
      chain (MyHC) isoform alterations during heart failure (HF) are not completely
      understood. We tested the hypothesis that diaphragm expression of mitogen
      activated protein kinases (MAPK) and myogenic regulatory factors is changed in
      rats with myocardial infarction (MI) induced HF. METHODS: Six months after MI
      rats were subjected to transthoracic echocardiography. After euthanasia,
      infarcted rats were subdivided in MI/HF- group (with no HF evidence; n=10), and
      MI/HF+ (with right ventricular hypertrophy and lung congestion; n=10). Sham
      operated rats were used as controls (n=10). MyHC isoforms were analyzed by
      electrophoresis. STATISTICAL ANALYSIS: ANOVA and Pearson correlation. RESULTS:
      MI/HF- had left cardiac chambers dilation with systolic and diastolic left
      ventricular dysfunction. Cardiac injury was more intense in MI/HF+ than MI/HF-.
      MyHC I isoform percentage was higher in MI/HF+ than MI/HF-, and IIb isoform lower
      in MI/HF+ than Sham. Left atrial diameter-to-body weight ratio positively
      correlated with MyHC I (p=0.005) and negatively correlated with MyHC IIb
      (p=0.02). TNF-alpha serum concentration positively correlated with MyHC I
      isoform. Total and phosphorylated ERK was lower in MI/HF- and MI/HF+ than Sham.
      Phosphorylated JNK was lower in MI/HF- than Sham. JNK and p38 did not differ
      between groups. Expression of NF-kappaB and the myogenic regulatory factors MyoD,
      myogenin, and MRF4 was similar between groups. CONCLUSION: Diaphragm MyHC fast-to
      slow shift is related to cardiac dysfunction severity and TNF-alpha serum levels
      in infarcted rats. Reduced ERK expression seems to participate in MyHC isoform
      changes. Myogenic regulatory factors and NF-kappaB do not modulate diaphragm MyHC
      distribution during chronic HF.

PMID- 25060723
TI  - Interventional treatment of atrial fibrillation - contemporary methods and
      perspectives.
AB  - Atrial fibrillation (AF) is estimated to affect nearly 3 million people around
      the world. It is the most common arrhythmia and its incidence increases with age.
      Catheter ablation is an interventional procedure performed to reduce the
      patient's AF burden when pharmacotherapy did not succeed in relieving the
      patient's symptoms. The ablation is most effective in paroxysmal AF; however,
      many techniques are being developed to make this procedure more eligible for
      patients with persistent arrhythmia. The most common AF ablation technique
      involves separating electric activity of the pulmonary veins from the left
      atrium. Over recent years, many novel and promising techniques were developed
      (e.g., balloon cryoablation, circular catheter ablation, laser ablation, robotic
      navigation, etc.), which may further improve AF ablation efficacy. 

PMID- 25060724
TI  - Radiotherapy for benign head and neck paragangliomas: a 45-year experience.
AB  - BACKGROUND: Paragangliomas of the head and neck are rare, slow-growing, generally
      benign tumors of neuroendocrine cells associated with the peripheral nervous
      system that commonly involve the carotid body, jugular bulb, vagal ganglia, and
      temporal bone. Treatment options include surgery, radiotherapy (RT), stereotactic
      radiosurgery (SRS), and observation. This article briefly reviews our 45-year
      institutional experience treating this neoplasm with RT. METHODS: From January
      1968 through March 2011, 131 patients with 156 benign paragangliomas of the
      temporal bone, carotid body, jugular bulb, or glomus vagale were treated with RT
      at a median dose of 45 Gy in 25 fractions. The mean and median follow-up times
      were 11.5 years and 8.7 years, respectively. RESULTS: Five tumors (3.2%) recurred
      locally after RT, all within 10 years of treatment. The overall local control
      rates at 5 and 10 years were 99% and 96%, respectively. The cause-specific
      survival rates at 5 and 10 years were 98% and 97%, respectively. The distant
      metastasis free survival rates at 5 and 10 years were 99% and 99%, respectively.
      The overall survival rates at 5 and 10 years were 91% and 72%, respectively.
      There were no severe complications. CONCLUSION: RT for benign head and neck
      paragangliomas is a safe and efficacious treatment associated with minimal
      morbidity. Surgery is reserved for patients in good health whose risk of
      associated morbidity is low. SRS may be suitable for patients with skull base
      tumors <3 cm where RT is logistically unsuitable. Observation is a reasonable
      option for asymptomatic patients with a limited life expectancy.

PMID- 25060725
TI  - Reflectometric interference spectroscopy-based immunosensing using immobilized
      antibody via His-tagged recombinant protein A.
AB  - The proposed approach demonstrated in this study provides an immunosensing system
      based on reflectometric interference spectroscopy (RIfS) in combination with an
      antibody immobilization method using histidine-tagged recombinant protein A.
      Carboxymethyldextran (CMD) was immobilized on a 3-aminopropyltriethoxysilane
      treated a silicon nitride-coated silicon wafer, followed by chelating histidine
      tagged recombinant protein A with copper (II) ions. The CMD-layer was found to be
      advantageous in terms of not only immobilization of histidine-tagged recombinant
      protein A-mediated an antibody against myoglobin (anti-Myo) but also prevention
      of non-specific binding of myoglobin. Myoglobin was repeatedly detected, and the
      apparent detection limit was 0.1 MUg mL(-1). The proposed RIfS-based protein
      sensing system, in conjunction with the easy preparation of silicon-based
      inexpensive immunosensing chips, is expected to be applicable for label-free
      optical detection for other proteins in various fields. 

PMID- 25060726
TI  - Differentiation of industrial sake yeast strains by a loop-mediated isothermal
      amplification method that targets the PHO3 gene.
AB  - We developed a loop-mediated isothermal amplification method that targets the
      PHO3 gene for discriminating sake yeast strains. Our data indicate that this
      assay is simple, rapid, and useful to use for differentiation of specific yeasts
      in sake mash. 

PMID- 25060727
TI  - Molecularly imprinted protein recognition thin films constructed by
      controlled/living radical polymerization.
AB  - We demonstrated the synthesis of molecularly imprinted polymers (MIPs) with
      binding affinity toward a target protein, ribonuclease A (RNase) by atom transfer
      radical polymerization (ATRP) of acrylic acid, acrylamide, and N,N'
      methylenebisacrylamide in the presence of RNase. The binding activity of the MIPs
      was evaluated by surface plasmon resonance (SPR) of the MIP thin layers prepared
      on the gold-coated sensor chips. The MIPs prepared by ATRP (MIP-ATRP) had a
      binding affinity toward RNase with larger binding amount compared to MIPs
      prepared by conventional free radical polymerization methods (MIP-RP). Moreover,
      protein selectivity was evaluated using reference proteins (cytochrome c,
      myoglobin, and alpha-lactalbumin) and was confirmed in MIP-ATRP of optimum film
      thickness determined experimentally to be 15-30 nm; however, protein selectivity
      was not achieved in all MIP-RP. We have shown that ATRP is powerful technique for
      preparing protein recognition materials by molecular imprinting. 

PMID- 25060728
TI  - Nano-scale liquid chromatography coupled to tandem mass spectrometry using the
      multiple reaction monitoring mode based quantitative platform for analyzing
      multiple enzymes associated with central metabolic pathways of Saccharomyces
      cerevisiae using ultra fast mass spectrometry.
AB  - A widely targeted quantitative proteome analysis of Saccharomyces cerevisiae
      enzymes was performed employing an ultra fast mass spectrometry (UFMS). Nano
      liquid chromatography-UFMS analysis of trypsin digested peptide samples derived
      from yeast strains successfully determined relative abundances of 303 peptides of
      137 proteins. 

PMID- 25060729
TI  - Gas chromatography/mass spectrometry based component profiling and quality
      prediction for Japanese sake.
AB  - Sake is a Japanese traditional alcoholic beverage, which is produced by
      simultaneous saccharification and alcohol fermentation of polished and steamed
      rice by Aspergillus oryzae and Saccharomyces cerevisiae. About 300 compounds have
      been identified in sake, and the contribution of individual components to the
      sake flavor has been examined at the same time. However, only a few compounds
      could explain the characteristics alone and most of the attributes still remain
      unclear. The purpose of this study was to examine the relationship between the
      component profile and the attributes of sake. Gas chromatography coupled with
      mass spectrometry (GC/MS)-based non-targeted analysis was employed to obtain the
      low molecular weight component profile of Japanese sake including both
      nonvolatile and volatile compounds. Sake attributes and overall quality were
      assessed by analytical descriptive sensory test and the prediction model of the
      sensory score from the component profile was constructed by means of orthogonal
      projections to latent structures (OPLS) regression analysis. Our results showed
      that 12 sake attributes [ginjo-ka (aroma of premium ginjo sake), grassy/aldehydic
      odor, sweet aroma/caramel/burnt odor, sulfury odor, sour taste, umami, bitter
      taste, body, amakara (dryness), aftertaste, pungent/smoothness and appearance]
      and overall quality were accurately explained by component profiles. In addition,
      we were able to select statistically significant components according to variable
      importance on projection (VIP). Our methodology clarified the correlation between
      sake attribute and 200 low molecular components and presented the importance of
      each component thus, providing new insights to the flavor study of sake. 

PMID- 25060730
TI  - Isolation and characterization of awamori yeast mutants with L-leucine
      accumulation that overproduce isoamyl alcohol.
AB  - Awamori shochu is a traditional distilled alcoholic beverage made from steamed
      rice in Okinawa, Japan. Although it has a unique aroma that is distinguishable
      from that of other types of shochu, no studies have been reported on the breeding
      of awamori yeasts. In yeast, isoamyl alcohol (i-AmOH), known as the key flavor of
      bread, is mainly produced from alpha-ketoisocaproate in the pathway of L-leucine
      biosynthesis, which is regulated by end-product inhibition of alpha
      isopropylmalate synthase (IPMS). Here, we isolated mutants resistant to the L
      leucine analog 5,5,5-trifluoro-DL-leucine (TFL) derived from diploid awamori
      yeast of Saccharomyces cerevisiae. Some of the mutants accumulated a greater
      amount of intracellular L-leucine, and among them, one mutant overproduced i-AmOH
      in awamori brewing. This mutant carried an allele of the LEU4 gene encoding the
      Ser542Phe/Ala551Val variant IPMS, which is less sensitive to feedback inhibition
      by L-leucine. Interestingly, we found that either of the constituent mutations
      (LEU4(S542F) and LEU4(A551V)) resulted in the TFL tolerance of yeast cells and
      desensitization to L-leucine feedback inhibition of IPMS, leading to
      intracellular L-leucine accumulation. Homology modeling also suggested that L
      leucine binding was drastically inhibited in the Ser542Phe, Ala551Val, and
      Ser542Phe/Ala551Val variants due to steric hindrance in the cavity of IPMS. As we
      expected, awamori yeast cells expressing LEU4(S542F), LEU4(A551V), and
      LEU4(S542F/A551V) showed a prominent increase in extracellular i-AmOH production,
      compared with that of cells carrying the vector only. The approach described here
      could be a practical method for the breeding of novel awamori yeasts to expand
      the diversity of awamori taste and flavor.

PMID- 25060731
TI  - Trehalose accumulation enhances tolerance of Saccharomyces cerevisiae to acetic
      acid.
AB  - Trehalose confers protection against various environmental stresses on yeast
      cells. In this study, trehalase gene deletion mutants that accumulate trehalose
      at high levels showed significant stress tolerance to acetic acid. The
      enhancement of trehalose accumulation can thus be considered a target in the
      breeding of acetic acid-tolerant yeast strains. 

PMID- 25060732
TI  - Graphene-supported tunable extraordinary transmission.
AB  - By depositing a graphene layer on the metallic film with subwavelength hole
      arrays, the tunable extraordinary transmission property based on the metal
      dielectrics-graphene (MDG) structure has been investigated in the terahertz (THz)
      and near-infrared (NIR) regimes. The influences of operation frequency, composed
      materials, and the Fermi level of the graphene layer have been taken into
      account. The results show that by varying the Fermi level of the graphene layer,
      the transmission of the MDG structure can be tuned in a wide range and the
      modulation depth of the peak value of the transmission can reach more than 50%.
      But the tunable mechanisms in the THz and NIR regimes are quite different. In the
      infrared (THz) regime, the graphene behaves like the dielectric (metallic) layer;
      its dielectric constant decreases (increases) with the increase of Fermi level,
      resulting in the transmission increasing (decreasing). Compared with the metallic
      structure, the transmission of the semiconductor structure can also be modulated
      by using the doping or varying temperature; its peak position can also be changed
      in a much broader range. The results are very useful to understand the mechanism
      of the graphene plasmonic devices and to design novel filters, switchers,
      modulators, and sensors. 

PMID- 25060733
TI  - Response.

PMID- 25060734
TI  - [Parasite authors or altruism in the peer-review process. The importance of
      authors also being reviewers].

PMID- 25060735
TI  - Trends of indigenous healing among people with psychiatric disorders: comparative
      study of Arabic and Kurdish ethnicities in Iraq.
AB  - Indigenous healing is commonly practiced in Middle East. Little is known about
      trends of indigenous therapies among patients with psychiatric disorders in Iraq.
      To determine and compare rates and predictors of indigenous healings by
      individuals with psychiatric disorders, and the practiced rituals among Arabic
      and Kurdish ethnicities in Iraq, patients aged 18 year and older attending
      outpatients in Erbil and Najaf were assessed for their prior contacts with
      indigenous healers. About 48.9 % had indigenous healer's consultations before
      visiting their psychiatrists; the figure was three times higher among Arabs than
      Kurds. Higher consultation rate was detected among younger and less formally
      educated patients. Fourteen types of religious therapeutic rituals have been
      practiced. Indigenous healing is widespread in Iraq. It is more common among
      Arabs, younger and less educated people with psychiatric disorders. Participants
      consider indigenous healing for their psychiatric more than non-psychiatric
      disorders.

PMID- 25060736
TI  - A preliminary trial of the sedation induced by intranasal administration of
      midazolam alone or in combination with dexmedetomidine and reversal by
      atipamezole for a short-term immobilization in pigeons.
AB  - OBJECTIVE: To assess the sedative and immobilization effect of intranasal
      administration (INS) of midazolam (MID) without or with INS dexmedetomidine
      (DXM), and some physiological changes induced by the drugs. The ability of INS
      atipamezole to reverse the DXM component was also assessed. STUDY DESIGN:
      Prospective 'blinded' experimental study. ANIMALS: In total, 15 pigeons. METHODS:
      Pigeons were sedated by INS MID alone at a dose of 5 mg kg(-1) (group MID, n = 6)
      or in combination with INS DXM at a dose 80 MUg kg(-1) (group MID-DXM, n = 6).
      Measurements were made of heart rate (HR), respiratory rate (fR ) and cloacal
      temperature (CT). The degree of sedation was assessed at 15 minutes prior to,
      immediately after, and at intervals until 100 minutes after drug administrations.
      Following MID-DXM, INS atipamezole (250 MUg kg(-1) ) was administered and the
      same indices measured 5 and 10 minutes later. RESULTS: MID had no effect on HR
      and fR , and although CT decreased, it remained within physiological range. MID
      DXM caused significant falls in HR, fR and CT that persisted until the end of
      sedation. Atipamezole antagonized sedation and cardiorespiratory side effects of
      MID-DXM within 10 minutes of application. In addition, for MID compared to MID
      DXM, the lowest sedation scores [10 (7-14) and 10.5 (5-14) versus 2 (1-4) and 2
      (1-5)] were achieved in the 10th and 20th minute versus the 20th and 30th minute
      of the sedation, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: MID alone,
      given INS had minimal side effects on vital functions but caused inadequate
      immobilization of pigeons for restraint in dorsal recumbency. MID-DXM caused an
      effective degree of immobilization from 20 to 30 minutes after administration, at
      which time birds tolerated postural changes without resistance. Atipamezole
      antagonized both side effects and sedation, but complete recovery had not
      occurred within 10 minutes after its application.

PMID- 25060737
TI  - Determination of caramel colorants' by-products in liquid foods by ultra-high
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
AB  - 2-Methylimidazole, 4-methylimidazole (2-MI and 4-MI), 2-acetyl-4-(1,2,3,4
      tetrahydroxybutyl) imidazole (THI) and 5-hydroxymethylfurfural (5-HMF) are neo
      formed compounds generated during the manufacture of caramel colours and are
      transferred to the processed food. These contaminants are known to have a
      toxicological profile that may pose health risks. Hence, to characterise THI, 2-
      and 4-MI and 5-HMF levels in liquid foods, an ultra-high-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and
      sample preparation was divided into two analytical strategies depending on the
      concentration range expected in the type of foods targeted. For the determination
      of the imidazole substitutes (THI, 2- and 4-MI), a sample enrichment and clean-up
      step by strong cation solid-phase extraction was developed. This method is
      capable of quantifying over a range of 5 ng ml-1 (LOQ) to 500 ng ml-1 with
      recoveries of 75.4-112.4% and RSDs of 1.5-15%. For determination of 5-HMF, a
      standard addition method was applied covering the linear range of 0.25-30 ug ml-1
      with RSDs from 2.8% (for intraday precision) to 9.2% (for intermediate
      precision). The validated analytical methods were applied to 28 liquid food
      samples purchased from local markets. THI was found only in the beer samples at
      levels up to 141.2 ng ml-1. For 2-MI, non-quantifiable traces were observed for
      all samples, while 4-MI was observed in all samples with large concentration
      variations (from < LOQ to 563.9 ng ml-1). 5-HMF was found at expected
      concentrations, except for a sherry vinegar sample (113 ug ml-1), which required
      a high level of dilution before following the standard addition protocol.

PMID- 25060738
TI  - The relationship between cognitive performance and insulin resistance in non
      diabetic patients with mild cognitive impairment.
AB  - OBJECTIVE: Insulin resistance (IR) is a distinct and early feature of type 2
      diabetes mellitus and metabolic syndrome. IR is thought to play a vital role in
      cognitive impairment. We conducted this study to understand the early
      characteristics of cognitive dysfunctions attributable to IR. METHODS: This study
      included 85 consecutive non-diabetic elderly participants with mild cognitive
      impairment (MCI). IR was estimated with the homeostasis model assessment of
      insulin resistance (HOMA-IR). Cognitive performances were analyzed as a function
      of scores on the HOMA-IR. RESULTS: The group analysis those with and without IR
      did not show any differences in the cognitive performance although higher HOMA-IR
      was closely associated with lower performances in immediate recall on the Seoul
      Verbal Learning Test (SVLT-I) (r = -0.244, p = 0.026) and Controlled Oral Word
      Association Test (COWAT) (r = -0.270, p = 0.013). In subgroup analysis by APOE
      status, SVLT-delayed (p = 0.027) and COWAT (p = 0.016) scores were found to be
      significantly lower in the IR than the non-IR among those with APOE epsilon4
      allele. In multiple regression analysis, impairment on the COWAT remained
      significantly correlated with scores on HOMA-IR (beta = -0.271, t = -2.340, p =
      0.022). However, IR status was identified to interact with APOE epsilon4
      carriership toward poor performances in the COWAT (beta = -0.335, t = -2.285, p =
      0.026). CONCLUSION: This study found a domain-specific impact of HOMA-IR scores
      on cognitive performances in non-diabetic patients with MCI. This association was
      profound only in APOE epsilon4carriers.

PMID- 25060739
TI  - The diabetic rat kidney mediates inosituria and selective urinary partitioning of
      D-chiro-inositol.
AB  - Diabetic nephropathy is a serious complication of diabetes mellitus with a
      pressing need for effective metabolic markers to detect renal impairment. Of
      potential significance are the inositol compounds, myo-inositol (MI), and the
      less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at
      increased levels in the urine in diabetes mellitus, a phenomenon known as
      inosituria. There is also a selective urinary excretion of DCI compared to MI. As
      the biological origins of altered inositol metabolism in diabetes mellitus are
      unknown, the aim of this study was to determine whether the diabetic kidney was
      directly responsible. Kidneys isolated from four-week streptozotocin-induced
      diabetic rats were characterized by a 3-fold reduction in glomerular filtration
      rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed
      quantities of MI (50 uM) and DCI (5 uM) under normoglycemic conditions (5 mM
      glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in
      diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary
      excretion of DCI was increased by 4-fold. Perfusion conditions replicating
      hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in
      both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in
      DCI urinary excretion compared to MI in diabetic kidneys that was independent of
      glucose ambience. This increased urinary excretion of DCI and MI in diabetic
      kidneys occurred despite increased renal expression of the inositol transporters,
      sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings
      show that the diabetic kidney primarily mediates inosituria and altered urinary
      partitioning of MI and DCI. Urinary inositol levels might therefore serve as an
      indicator of impaired renal function in diabetes mellitus with wider implications
      for monitoring chronic kidney disease.

PMID- 25060740
TI  - Body shape shifting during growth permits tests that distinguish between
      competing geometric theories of metabolic scaling.
AB  - Metabolism fuels all of life's activities, from biochemical reactions to
      ecological interactions. According to two intensely debated theories, body size
      affects metabolism via geometrical influences on the transport of resources and
      wastes. However, these theories differ crucially in whether the size dependence
      of metabolism is derived from material transport across external surfaces, or
      through internal resource-transport networks. We show that when body shape
      changes during growth, these models make opposing predictions. These models are
      tested using pelagic invertebrates, because these animals exhibit highly variable
      intraspecific scaling relationships for metabolic rate and body shape. Metabolic
      scaling slopes of diverse integument-breathing species were significantly
      positively correlated with degree of body flattening or elongation during
      ontogeny, as expected from surface area theory, but contradicting the negative
      correlations predicted by resource-transport network models. This finding
      explains strong deviations from predictions of widely adopted theory, and
      underpins a new explanation for mass-invariant metabolic scaling during ontogeny
      in animals and plants. 

PMID- 25060741
TI  - Structure of the pneumococcal l,d-carboxypeptidase DacB and pathophysiological
      effects of disabled cell wall hydrolases DacA and DacB.
AB  - Bacterial cell wall hydrolases are essential for peptidoglycan turnover and
      crucial to preserve cell shape. The d,d-carboxypeptidase DacA and l,d
      carboxypeptidase DacB of Streptococcus pneumoniae function in a sequential
      manner. Here, we determined the structure of the surface-exposed lipoprotein
      DacB. The crystal structure of DacB, radically different to that of DacA,
      contains a mononuclear Zn(2+) catalytic centre located in the middle of a large
      and fully exposed groove. Two different conformations were found presenting a
      different arrangement of the active site topology. The critical residues for
      catalysis and substrate specificity were identified. Loss-of-function of DacA and
      DacB altered the cell shape and this was consistent with a modified peptidoglycan
      peptide composition in dac mutants. Contrary, an lgt mutant lacking lipoprotein
      diacylglyceryl transferase activity required for proper lipoprotein maturation
      retained l,d-carboxypeptidase activity and showed an intact murein sacculus. In
      addition we demonstrated pathophysiological effects of disabled DacA or DacB
      activities. Real-time bioimaging of intranasal infected mice indicated a
      substantial attenuation of DeltadacB and DeltadacADeltadacB pneumococci, while
      DeltadacA had no significant effect. In addition, uptake of these mutants by
      professional phagocytes was enhanced, while the adherence to lung epithelial
      cells was decreased. Thus, structural and functional studies suggest DacA and
      DacB as optimal drug targets. 

PMID- 25060743
TI  - Psychiatric and self-injury profiles of adolescent suicide attempters versus
      adolescents engaged in nonsuicidal self-injury.
AB  - To better delineate the unique correlates of self-injurious behaviors (SIB),
      psychiatric profiles of mutually exclusive groups of adolescents who made a
      suicide attempt (SA) versus those engaged in nonsuicidal self-injury (NSSI) were
      examined. Contrary to hypotheses, the NSSI group endorsed earlier onsets of SIB
      and suicidal ideation (SI), as well as higher rates of depression and anxiety
      compared with their SA counterparts. Future work is warranted to understand the
      role of SI, including duration of SI and anxiety in the development of NSSI, and
      to identify risk and resiliency factors useful in predicting an adolescent's SIB
      status. 

PMID- 25060742
TI  - Biofilm removal and antimicrobial activity of two different air-polishing
      powders: an in vitro study.
AB  - BACKGROUND: Biofilm removal plays a central role in the prevention of periodontal
      and peri-implant diseases associated with microbial infections. Plaque
      debridement may be accomplished by air polishing using abrasive powders. In this
      study, a new formulation consisting of erythritol and chlorhexidine is compared
      with the standard glycine powder used in air-polishing devices. Their in vitro
      antimicrobial and antibiofilm effects on Staphylococcus aureus, Bacteroides
      fragilis, and Candida albicans are investigated. METHODS: Biofilm was allowed to
      grow on sandblasted titanium disks and air polished with glycine or erythritol
      chlorhexidine powders. A semiquantitative analysis of biofilm by
      spectrophotometric assay was performed. A qualitative analysis was also carried
      out by confocal laser scanning microscopy. Minimum inhibitory concentrations and
      minimum microbicidal concentrations were evaluated, together with the microbial
      recovery from the residual biofilm after air-polishing treatment. RESULTS: The
      combination of erythritol and chlorhexidine displayed stronger antimicrobial and
      antibiofilm activity than glycine against all microbial strains tested.
      CONCLUSION: Air polishing with erythritol-chlorhexidine seems to be a viable
      alternative to the traditional glycine treatment for biofilm removal.

PMID- 25060744
TI  - Activation of the proapoptotic unfolded protein response in plaques of the human
      carotid artery.
AB  - OBJECTIVE: To analyze expression of keystone markers of apoptosis and the
      proapoptotic signaling pathway "unfolded protein response" (UPR) in rupture-prone
      plaques of the human carotid artery. METHODS: Plaque specimens were obtained
      during endarterectomy for high-grade carotid stenosis, and were formalin-fixed.
      Ten specimens were identified that exhibited criteria of advanced rupture-prone
      atherosclerotic plaques, and histological and immunohistological analysis of
      markers of apoptosis (cleaved Caspase-3, TUNEL) and UPR (KDEL, ATF3, CHOP, CHAC
      1) was performed. In addition, co-localization of apoptosis and UPR-activation
      was assessed by double-immunohistochemistry. RESULTS: The mean size of the
      necrotic core was 44 +/- 7% and the mean minimum/representative thicknesses of
      the fibrous cap were 129 +/- 39 MUm/280 +/- 60 MUm, respectively. Each specimen
      fulfilled at least two of the criteria for rupture-prone plaques. Semi
      quantitative analysis of immunohistochemistry showed a significant increase in
      cleaved Caspase-3-positive (1923 +/- 93 cells/mm(2)) and TUNEL-positive cells
      (1387 +/- 66 cells/mm(2)) when compared with control tissue. Furthermore,
      expression of UPR-markers KDEL, AFT3 and CHOP was significantly increased (1175
      +/- 40 cells/mm(2), 1971 +/- 69 cells/mm(2) and 2173 +/- 120 cells/mm(2),
      respectively). Co-localization of UPR-activation with apoptosis was confirmed by
      double-immunohistochemistry, and lesional macrophages were identified as the
      primary cell-type involved. CONCLUSION: For the first time, activation of the
      proapoptotic signaling pathway UPR has been identified in advanced rupture-prone
      plaques of the human carotid artery. This provides additional evidence for adding
      UPR to the potential targets for controlling plaque apoptosis and thereby
      preventing plaque progression/rupture.

PMID- 25060745
TI  - Shape memory particles capable of controlled geometric and chemical asymmetry
      made from aliphatic polyesters.
AB  - A novel method for producing monodisperse micro- and nanosized shape memory
      particles from various shape memory polymers (SMPs) is reported. This method uses
      a polydimethylsiloxane mold to uniformly deform particles from complex shapes to
      other well-defined shapes, harvest them without aggressive solvents or heat, and
      then return them to their original shapes upon heating above a preselected
      trigger temperature. By manipulating the material properties of both the mold and
      SMP, monodisperse asymmetric particles are easily achieved. This method is
      demonstrated with traditional SMPs and polymers with varying degrees of reactive
      functionality, crystallinity, and transition temperature. This additional
      reactivity and the robustness of this system allow easy tailoring of the surface
      with click chemistry to achieve chemical asymmetry. 

PMID- 25060746
TI  - Tissue engineering strategies for fetal myelomeningocele repair in animal models.
AB  - Myelomeningocele (MMC), the most severe form of spina bifida, is a common and
      devastating malformation. Over two decades of experimental work in animal models
      have led to the development and clinical application of open fetal surgery for
      the repair of the MMC defect. This approach offers improved neurofunctional
      outcomes and is now a clinical option for the management of prenatally diagnosed
      MMC in selected patients. However, there are still opportunities for further
      improvement in the prenatal treatment of MMC. A less invasive approach would
      allow for an application earlier in gestation, with a reduction in maternal and
      fetal risks and the potential for reduced neurological injury. Tissue engineering
      offers a realistic and appealing alternative approach for the prenatal treatment
      of MMC. This review discusses the rationale for tissue engineering in MMC,
      addresses recent experimental progress and describes potential future directions.

PMID- 25060747
TI  - Effectiveness of Day Hospital Mentalization-Based Treatment for Patients with
      Severe Borderline Personality Disorder: A Matched Control Study.
AB  - The present study extends the body of evidence regarding the effectiveness of day
      hospital Mentalization-Based Treatment (MBT) by documenting the treatment outcome
      of a highly inclusive group of severe borderline personality disorder (BPD)
      patients, benchmarked by a carefully matched group who received other specialized
      psychotherapeutic treatments (OPT). Structured diagnostic interviews were
      conducted to assess diagnostic status at baseline. Baseline, 18-month treatment
      outcome and 36-month treatment outcome (after the maintenance phase) on
      psychiatric symptoms (Brief Symptom Inventory) and personality functioning (118
      item Severity Indices of Personality Problems) were available for 29 BPD patients
      assigned to MBT, and an initial set of 175 BPD patients assigned to OPT.
      Propensity scores were used to determine the best matches for the MBT patients
      within the larger OPT group, yielding 29 MBT and 29 OPT patients for direct
      comparison. Treatment outcome was analysed using multilevel modelling. Pre to
      post effect sizes were consistently (very) large for MBT, with a Cohen's d of 
      1.06 and -1.42 for 18 and 36 months, respectively, for the reduction in
      psychiatric symptoms, and ds ranging from 0.81 to 2.08 for improvement in domains
      of personality functioning. OPT also yielded improvement across domains but
      generally of moderate magnitude. In conclusion, the present matched control
      study, executed by an independent research institute outside the UK, demonstrated
      the effectiveness of day hospital MBT in a highly inclusive and severe group of
      BPD patients, beyond the benchmark provided by a mix of specialized psychotherapy
      programmes. Interpretation of the (large) between condition effects warrants
      cautionary caveats given the non-randomized design, as well as variation in
      treatment dosages.

PMID- 25060749
TI  - Two-stage microfluidic chip for selective isolation of circulating tumor cells
      (CTCs).
AB  - Over the past few decades, circulating tumor cells (CTCs) have been studied as a
      means of overcoming cancer. However, the rarity and heterogeneity of CTCs have
      been the most significant hurdles in CTC research. Many techniques for CTC
      isolation have been developed and can be classified into positive enrichment
      (i.e., specifically isolating target cells using cell size, surface protein
      expression, and so on) and negative enrichment (i.e., specifically eluting non
      target cells). Positive enrichment methods lead to high purity, but could be
      biased by their selection criteria, while the negative enrichment methods have
      relatively low purity, but can isolate heterogeneous CTCs. To compensate for the
      known disadvantages of the positive and negative enrichments, in this study we
      introduced a two-stage microfluidic chip. The first stage involves a microfluidic
      magnetic activated cell sorting (MU-MACS) chip to elute white blood cells (WBCs).
      The second stage involves a geometrically activated surface interaction (GASI)
      chip for the selective isolation of CTCs. We observed up to 763-fold enrichment
      in cancer cells spiked into 5 mL of blood sample using the MU-MACS chip at 400
      MUL/min flow rate. Cancer cells were successfully separated with separation
      efficiencies ranging from 10.19% to 22.91% based on their EpCAM or HER2 surface
      protein expression using the GASI chip at a 100 MUL/min flow rate. Our two-stage
      microfluidic chips not only isolated CTCs from blood cells, but also classified
      heterogeneous CTCs based on their characteristics. Therefore, our chips can
      contribute to research on CTC heterogeneity of CTCs, and, by extension,
      personalized cancer treatment.

PMID- 25060750
TI  - CT sensitivities for large (>=3 cm) adrenal adenoma and cortical carcinoma.
AB  - PURPOSE: To retrospectively compare computed tomography (CT) sensitivities of
      large (>=3 cm) adenoma and cortical carcinoma. METHODS: Between January 2004 and
      November 2012, 43 non-oncologic patients with 43 adrenal masses [31 large
      adenomas, and 12 carcinomas] underwent unenhanced CT, early contrast-enhanced CT,
      and delayed contrast-enhanced CT scans prior to adrenalectomy. Three types of
      region-of-interest (ROI) were used on early contrast-enhanced CT images:aROI
      (large ROI) covering more than half of a mass and two small ROIs fitted to the
      highest (high ROI) or lowest (low ROI) attenuation area. These ROIs were also
      placed in the same area on the other CT images. Adenoma was diagnosed if a mass
      measured <=10 HU on unenhanced CT image, or if it had >=60% absolute percentage
      washout (APW)or >=40% relative percentage washout (RPW).Carcinoma was diagnosed
      if a mass had <60% APW and <40% RPW. CT sensitivities for large adenoma and
      carcinoma were compared. RESULTS: CT sensitivities for large adenoma vs.
      carcinoma were 64.5% (20/31) vs. 100% (12/12) using a large ROI, 100% (31/31) vs.
      50.0% (6/12) using a high ROI, and 51.6% (16/31) vs. 100% (12/12) using a low
      ROIs, respectively. CONCLUSIONS: CT sensitivities for large adenoma and cortical
      carcinoma are influenced by the size or location of an ROI.A large ROI helps to
      minimize loss of CT sensitivity for large adenoma and to detect carcinoma.

PMID- 25060748
TI  - Apogossypolone inhibits the proliferation of LNCaP cells in vitro and in vivo.
AB  - The aim of the present study was to investigate the anti-tumor effect of
      apogossypolone (ApoG2) on human LNCaP cells in vitro and in vivo. Cell viability
      was evaluated using an MTT assay. Cell autophagy and apoptosis were detected by
      flow cytometry and using a terminal deoxynucleotidyl transferase dUTP nick end
      labeling assay, respectively. Morphological autophagy alterations were observed
      by transmission electron microscopy. The formation of acidic vesicular organelles
      was assessed by acridine orange staining and fluorescence microscopy.
      Quantitative polymerase chain reaction (qPCR) was conducted to detect the
      expression levels of apoptosis-associated protein B-cell lymphoma 2 (Bcl-2) and
      Bak. The models of transplantation tumors in nude mice were established via
      subcutaneous injection of LNCaP cells. Growth of LNCaP cells was inhibited by
      ApoG2 treatment. Flow cytometry demonstrated that ApoG2 induced apoptosis in
      LNCaP cells. The Bcl-2 expression was decreased while Bak expression was
      increased. In addition, activation of cysteine aspartate protease (caspase)-3 and
      -8 was observed and 3-methyladenine (3-MA) enhanced apoptosis of LNCaP cells.
      Furthermore, nude mice treated with ApoG2 demonstrated a significant decrease in
      tumor volume and a significant increase in cell viability. Immunohistochemical
      analysis of tumor tissues demonstrated that ApoG2 enhanced caspase-3, -8, LC-3B
      and beclin-1 expression and reduced the expression of Bcl-2. ApoG2 was able to
      effectively suppress the growth of LNCaP cells through the induction of autophagy
      and apoptosis.

PMID- 25060751
TI  - Strategies for recruitment of relatives of BRCA mutation carriers to a genetic
      testing program in the Bahamas.
AB  - The prevalence of BRCA1 and BRCA2 mutations among unselected breast cancer
      patients in the Bahamas is 23%. It is beneficial to advise relatives of mutation
      carriers that they are candidates for genetic testing. Women who test positive
      are then eligible for preventive interventions, such as oophorectomy. It is not
      clear how often relatives of women with a mutation in the Bahamas wish to undergo
      genetic testing for the family mutation. Furthermore, it is not clear how best to
      communicate this sensitive information to relatives in order to maximize patient
      compliance. We offered genetic testing to 202 first-degree relatives of 58
      mutation carriers. Of 159 women who were contacted by the proband or other family
      member, only 14 made an appointment for genetic testing (9%). In contrast, among
      32 relatives who were contacted directly by the genetic counselor, 27 came for an
      appointment (84%). This study suggests that for recruitment of relatives in the
      Bahamas, direct contact by counselor is preferable to using the proband as an
      intermediary. 

PMID- 25060752
TI  - [FEES for neurogenic dysphagia: training curriculum of the German Society of
      Neurology and the German Stroke Society].
AB  - Neurogenic dysphagia is one of the most frequent and prognostically relevant
      neurological deficits in a variety of disorders, such as stroke, parkinsonism and
      advanced neuromuscular diseases. Flexible endoscopic evaluation of swallowing
      (FEES) is now probably the most frequently used tool for objective dysphagia
      assessment in Germany. It allows evaluation of the efficacy and safety of
      swallowing, determination of appropriate feeding strategies and assessment of the
      efficacy of different swallowing manoeuvres. The literature furthermore indicates
      that FEES is a safe and well-tolerated procedure. In spite of the huge demand for
      qualified dysphagia diagnostics in neurology, a systematic FEES education has yet
      not been established. The structured training curriculum presented in this
      article aims to close this gap and intends to enforce a robust and qualified FEES
      service. As management of neurogenic dysphagia is not confined to neurologists,
      this educational program is applicable to other clinicians and speech language
      therapists with expertise in dysphagia as well. 

PMID- 25060753
TI  - Stability-indicating liquid chromatographic method for determination of
      saxagliptin and structure elucidation of the major degradation products using LC
      MS.
AB  - A new, simple, selective, reproducible and sensitive stability-indicating liquid
      chromatographic method was developed and subsequently validated for the
      determination of saxagliptin (SXG). SXG was subjected to oxidation, thermal, acid
      hydrolysis, alkali hydrolysis and photodegradation according to ICH guidelines.
      The major degradation products were separated from the pure drug and the proposed
      structures' elucidation was performed, using an LC-MS technique. Isocratic
      chromatographic elution was achieved on a Symmetry((r)) C18 column (150 * 4.6 mm,
      5 um), using a mobile phase of potassium dihydrogen phosphate buffer (pH 4.6)
      acetonitrile-methanol (40 : 30 : 30, v/v/v) at a flow rate of 1 mL min(-1) with
      UV detection at 208 nm. Linearity, accuracy and precision were found to be
      acceptable over the concentration range of 25-400 ug mL(-1). All the results were
      statistically compared with the reference method, using one-way analysis of
      variance. The developed method was validated and proved to be specific and
      accurate for quality control of SXG in pharmaceutical dosage form. 

PMID- 25060754
TI  - Mechanisms of aortic aneurysm formation: translating preclinical studies into
      clinical therapies.
AB  - Aneurysms are common in the abdominal and thoracic regions of the aorta. While
      generally asymptomatic, progression of aneurysms is associated with the
      devastating consequences of aortic rupture. Current therapeutic options to
      prevent rupture are restricted to surgical repair, as there remains a lack of
      validated pharmaceutical approaches. Absence of proven medical therapies may be a
      consequence of the paucity of knowledge on mechanisms of aneurysmal initiation,
      progression and rupture. Many potential therapeutic targets have been identified
      in several widely used animal models of these diseases. A small number of these
      targets are currently under clinical evaluation, while many more are in
      preclinical stages of evaluation. The purpose of this review is to: (1) overview
      current understanding of mechanisms of aneurysmal initiation and progression and
      (2) summarise medical therapies that have been investigated clinically, as well
      as highlight future therapeutic targets. 

PMID- 25060755
TI  - Aortic regurgitation severity after transcatheter aortic valve implantation is
      underestimated by echocardiography compared with MRI.
AB  - OBJECTIVE: Aortic regurgitation (AR) after transcatheter aortic valve
      implantation (TAVI) is associated with a poor clinical outcome and its assessment
      therefore crucial. Quantification of AR by transthoracic echocardiography (TTE),
      however, remains challenging in this setting. The present study used quantitative
      flow measurement by cardiac MRI (CMR) with calculation of regurgitant fraction
      (RF) for the assessment of AR and compared the results with TTE. METHODS AND
      RESULTS: We included 65 patients with a mean age of 82.2+/-8.1 years (38 women)
      who underwent successful TAVI with Edwards SAPIEN valves (52 transfemoral, 13
      transapical). The post-interventional degree of AR was assessed by CMR and by
      TTE. There was agreement between CMR and TTE with regards to the absence of
      severe AR. However, TTE significantly underestimated the presence of moderate AR
      classifying it to be mild in 38 and moderate in only 5 patients, whereas CMR
      found mild AR in 23 and moderate in 16 patients. Overall, there was only fair
      agreement between CMR and TTE regarding the grading of AR with a weighted kappa
      of 0.33. The rate of detection of TTE for more than mild AR was only 19%.
      CONCLUSIONS: Using CMR for the quantification of AR in a sizeable group of TAVI
      patients, we demonstrate a strong tendency of TTE to underestimate AR compared
      with CMR. Since higher AR severity on echocardiography has been associated with
      worse patient outcome, the potential incremental prognostic value of CMR should
      be studied prospectively in this setting.

PMID- 25060756
TI  - beta-blockers for secondary prevention in stable coronary artery disease: can
      observational studies provide valid answers?

PMID- 25060757
TI  - Sex as a determinant of prehospital ECG in ST- and non-ST elevation myocardial
      infarction patients.

PMID- 25060759
TI  - Glucosinolate profile and distribution among plant tissues and phenological
      stages of field-grown horseradish.
AB  - Profile and distribution of glucosinolates (GLS) were detected in plant tissues
      of horseradish at different developmental stages: beginning of vegetative re
      growth, flowering and silique formation. The GLS profile varied widely in the
      different tissues: we identified 17 GLS in roots and sprouts, one of which was
      not previously characterized in horseradish, i.e. the 2(S)-hydroxy-2-phenylethyl
      GLS (glucobarbarin) and/or 2(R)-hydroxy-2-phenylethyl-GLS (epiglucobarbarin), 11
      already found in the roots, including the putative 2-methylsulfonyl-oxo-ethyl
      GLS, and 5 previously recognized only in the sprouts. Fifteen of those GLS were
      also identified in young and cauline leaves, 12 in the mature leaves and 13 in
      the inflorescences. No difference in GLS profile was observed in plant among the
      phenological stages. Differences in concentrations of GLS, quantified as
      desulfated, were found in plant. At the beginning of vegetative re-growth,
      sprouts while showing the same profile of the roots were much richer in GLS
      having the highest total GLS concentrations (117.5 and 7.7MUmolg(-1) dry weight
      in sprouts and roots, respectively). During flowering and silique forming stages,
      the roots still maintained lower amount of total GLS (7.4MUmolg(-1) of dry
      weight, on average) with respect to the epigeous tissues, in which mature and
      young leaves showed the highest total concentrations (70.5 and 73.8MUmolg(-1) of
      dry weight on average, respectively). Regardless of the phenological stages, the
      aliphatic GLS were always predominant in all tissues (95%) followed by indolic
      (2.6%) and benzenic (2.4%) GLS. Sinigrin contributed more than 90% of the total
      GLS concentration. Aliphatic GLS concentrations were much higher in the epigeous
      tissues, particularly in the mature and young leaves, while benzenic and indolic
      GLS concentrations were higher in the roots. Through the phenological stages, GLS
      concentration increased in young and mature leaves and decreased in cauline
      leaves and inflorescences, while it remained constant over time in roots.

PMID- 25060758
TI  - Annotation of the zebrafish genome through an integrated transcriptomic and
      proteomic analysis.
AB  - Accurate annotation of protein-coding genes is one of the primary tasks upon the
      completion of whole genome sequencing of any organism. In this study, we used an
      integrated transcriptomic and proteomic strategy to validate and improve the
      existing zebrafish genome annotation. We undertook high-resolution mass
      spectrometry-based proteomic profiling of 10 adult organs, whole adult fish body,
      and two developmental stages of zebrafish (SAT line), in addition to
      transcriptomic profiling of six organs. More than 7,000 proteins were identified
      from proteomic analyses, and ~ 69,000 high-confidence transcripts were assembled
      from the RNA sequencing data. Approximately 15% of the transcripts mapped to
      intergenic regions, the majority of which are likely long non-coding RNAs. These
      high-quality transcriptomic and proteomic data were used to manually reannotate
      the zebrafish genome. We report the identification of 157 novel protein-coding
      genes. In addition, our data led to modification of existing gene structures
      including novel exons, changes in exon coordinates, changes in frame of
      translation, translation in annotated UTRs, and joining of genes. Finally, we
      discovered four instances of genome assembly errors that were supported by both
      proteomic and transcriptomic data. Our study shows how an integrative analysis of
      the transcriptome and the proteome can extend our understanding of even well
      annotated genomes.

PMID- 25060760
TI  - Normal values for urine renalase excretion in children.
AB  - BACKGROUND: The objective of this study was to establish age-dependent values for
      urinary renalase/creatinine (renalase/Cr) ratio in healthy children and
      adolescents. METHODS: The study was conducted on a random sample of 157 healthy
      children and adolescents (0.1-17.9 years) divided into six age groups in 3-year
      intervals. Urine renalase concentration was measured using an enzyme-linked
      immunosorbent assay (ELISA) kit (Uscn Life Science, Wuhan, China). RESULTS: We
      analyzed median urine renalase/Cr ratio in particular age groups with the use of
      analysis of variance (ANOVA). Renalase/Cr levels were significantly higher in the
      youngest children < 3 years in comparison with other age groups (4.07 ng/mg Cr, p
      < 0.05). There was a statistically significant negative correlation between urine
      renalase/Cr and body mass index (BMI) Z-score (r = -0.22, p < 0.05) and both
      systolic (r = -0.22, p < 0.05) and diastolic (r = -0.21, p < 0.05) blood
      pressure. We constructed the reference renalase/Cr percentiles according to age
      in 3-year intervals. CONCLUSIONS: To the best of our knowledge, this study is the
      first to present reference values of urine renalase excretion in a healthy
      pediatric population. Further studies should concentrate on the influence of
      increased blood pressure or obesity on urine renalase excretion in children and
      teenagers.

PMID- 25060761
TI  - Urinary biomarkers for early diabetic nephropathy: beyond albuminuria.
AB  - Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease in
      the USA and accounts for a significant increase in morbidity and mortality in
      patients with diabetes. Early detection is critical in improving clinical
      management. Although microalbuminuria is regarded as the gold standard for
      diagnosing the onset of DN, its predictive powers are limited. Consequently,
      great efforts have been made in recent years to identify better strategies for
      the detection of early stages of DN and progressive kidney function decline in
      diabetic patients. Here, we review the various urinary biomarkers that have
      emerged from these studies which hold promise as more sensitive diagnostic tools
      for the earlier detection of diabetic kidney disease and the prediction of
      progression to end-stage kidney disease. A number of key biomarkers present in
      the urine have been identified that reflect kidney injury at specific sites along
      the nephron, including glomerular/podocyte damage and tubular damage, oxidative
      stress, inflammation and activation of the intrarenal renin-angiotensin system.
      We also describe newer approaches, including urinary microRNAs, which are short
      noncoding mRNAs that regulate gene expression, and urine proteomics, that can be
      used to identify potential novel biomarkers in the development and progression of
      diabetic kidney disease. 

PMID- 25060762
TI  - Paediatrics, insulin resistance and the kidney.
AB  - Systemic insulin resistance is becoming more prevalent in the young due to modern
      lifestyles predisposing to the metabolic syndrome and obesity. There is also
      evidence that there are critical insulin-resistant phases for the developing
      child, including puberty, and that renal disease per se causes systemic insulin
      resistance. This review considers the factors that render children insulin
      resistant, as well as the accumulating evidence that the kidney is an insulin
      responsive organ and could be affected by insulin resistance. 

PMID- 25060763
TI  - Inbreeding and inbreeding depression in endangered red wolves (Canis rufus).
AB  - In natural populations, the expression and severity of inbreeding depression can
      vary widely across taxa. Describing processes that influence the extent of
      inbreeding and inbreeding depression aid in our understanding of the evolutionary
      history of mating systems such as cooperative breeding and nonrandom mate
      selection. Such findings also help shape wildlife conservation theory because
      inbreeding depression reduces the viability of small populations. We evaluated
      the extent of inbreeding and inbreeding depression in a small, re-introduced
      population of red wolves (Canis rufus) in North Carolina. Since red wolves were
      first re-introduced in 1987, pedigree inbreeding coefficients (f) increased
      considerably and almost every wild born wolf was inbred (average f = 0.154 and
      max f = 0.383). The large inbreeding coefficients were due to both background
      relatedness associated with few founders and numerous close relative matings.
      Inbreeding depression was most evident for adult body size and generally absent
      for direct fitness measures such as reproductive success and survival; no lethal
      equivalents (LE = 0.00) were detected in juvenile survival. The lack of strong
      inbreeding depression in direct measures of fitness could be due to a founder
      effect or because there were no outbred individuals for comparison. Our results
      highlight the variable expression of inbreeding depression across traits and the
      need to measure a number of different traits when evaluating inbreeding
      depression in a wild population.

PMID- 25060764
TI  - Erythropoietin treatment in patients with myelodysplastic syndromes and type 2
      diabetes.
AB  - BACKGROUND: The aim of the present study was to assess the role of a concomitant
      type 2 diabetes as a potentially negative factor in the management of low-risk
      myelodysplastic syndrome (MDS) patients treated with high-dose (40,000 UI s.c. 2
      times/week) recombinant human erythropoietin (EPO) alpha (rHuEPO alpha). METHODS:
      One hundred and forty patients (M/F 69/71, median age 76, interquartile range
      [IR] 68-81) were included in the analysis: 27/140 (19.2%) had a concomitant type
      2 diabetes. RESULTS: No difference was reported between patients with and without
      diabetes as to the grade of anemia, the EPO endogenous levels and the need for
      transfusional requirement at baseline. Erythroid response was achieved in 79/140
      patients (56.4%): factors associated with response were lower EPO levels (P <
      0.0001), higher baseline Hb levels (P < 0.0001) and transfusion independence (P <
      0.0001). Diabetes was not predictive of response: 17/27 (62.9%) patients with
      diabetes were responsive to high-dose EPO compared with 62/113 (54.8%) patients
      without diabetes (P = 0.446). This was confirmed in multivariate analysis,
      controlling for the effects of Hb levels, transfusion-dependence and serum EPO
      levels. No difference was observed in relapse rate, response duration and OS
      between patients with and without diabetes. CONCLUSIONS: Concomitant type 2
      diabetes was not a major concern in the management of MDS patients.

PMID- 25060765
TI  - Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis
      B HBeAg negative with PEG-interferon.
AB  - In HBV-infected patients, the vitamin D deficiency has been related to chronic
      liver diseases, progression of hepatic fibrosis and poor response to the
      treatment. The CYP27B1 gene, which encodes the 1-alpha-hidroxylase and involved
      in the 1,25-dihydroxyvitamin D synthesis, was recently associated to type-1
      diabetes, autoimmune disorders and treatment response in HCV. Then, we aimed to
      investigate the role of CYP27B1 polymorphisms in HBV treatment with PEG-IFN. We
      retrospectively enrolled 190 patients with chronic hepatitis B HBeAg negative
      treated for 48 weeks with PEG-IFN alpha-2a. We examined the role of rs4646536
      CYP27B1 SNP (CYP27B1+2838) according to virological and serological response. Our
      results showed that the TT genotype of CYP27B1+2838 was significantly prevalent
      in patients with end-of-therapy virological response (37.6%) vs CT/CC (9.4%) (P <
      0.001). Virological relapse was prevalent in patients with CT/CC genotype (12.6%)
      vs TT genotype (2.1%) (P < 0.001). TT genotype was also related to HBsAg loss (P
      = 0.004) and anti-HBs appearance (P = 0.002). In the multivariate analysis, the
      TT genotype resulted to be a good positive predictor of sustained virological
      response (OR = 5.632, IC = 1.938-16.368, P = 0.001) and serological response (OR
      = 6.161, IC = 1.856-20.457, P = 0.003). The CYP27B1+2838 polymorphism may be
      useful as pretreatment factor to selection of patients with higher probability of
      response to therapy.

PMID- 25060767
TI  - Changes in histone methylation and acetylation during microspore reprogramming to
      embryogenesis occur concomitantly with Bn HKMT and Bn HAT expression and are
      associated with cell totipotency, proliferation, and differentiation in Brassica
      napus.
AB  - In response to stress treatments, microspores can be reprogrammed to become
      totipotent cells that follow an embryogenic pathway producing haploid and double
      haploid embryos which are important biotechnological tools in plant breeding.
      Recent studies have revealed the involvement of DNA methylation in regulating
      this process, but no information is available on the role of histone
      modifications in microspore embryogenesis. Histone modifications are major
      epigenetic marks controlling gene expression during plant development and in
      response to environmental changes. Lysine methylation of histones, accomplished
      by histone lysine methyltransferases (HKMTs), can occur on different lysine
      residues, with histone H3K9 methylation being mainly associated with
      transcriptionally silenced regions. In contrast, histone H3 and H4 acetylation is
      carried out by histone acetyltransferases (HATs) and is associated with actively
      transcribed genes. In this work, we analyzed 3 different histone epigenetic
      marks: dimethylation of H3K9 (H3K9me2) and acetylation of H3 and H4 (H3Ac and
      H4Ac) during microspore embryogenesis in Brassica napus by Western blot and
      immunofluorescence assays. The expression patterns of histone methyltransferase
      BnHKMT and histone acetyltransferase BnHAT genes have also been analyzed by qPCR.
      Our results revealed different spatial and temporal distribution patterns for
      methylated and acetylated histone variants during microspore embryogenesis and
      their similarity with the expression profiles of BnHKMT and BnHAT, respectively.
      The data presented suggest the participation of H3K9me2 and HKMT in embryo cell
      differentiation and heterochromatinization events, whereas H3Ac, H4Ac, and HAT
      would be involved in transcriptional activation, totipotency, and proliferation
      events during cell reprogramming and embryo development.

PMID- 25060766
TI  - MiR-17-5p modulates osteoblastic differentiation and cell proliferation by
      targeting SMAD7 in non-traumatic osteonecrosis.
AB  - MicroRNAs (miRNAs) have recently been recognized to have a role in human
      orthopedic disorders. The objective of our study was to explore the expression
      profile and biological function of miRNA-17-5p (miR-17-5p), which is well known
      to be related to cancer cell proliferation and invasion, in osteoblastic
      differentiation and in cell proliferation. The expression levels of miR-17-5p in
      the femoral head mesenchymal stem cells of 20 patients with non-traumatic
      osteonecrosis (ON) and 10 patients with osteoarthritis (OA) were examined by
      quantitative reverse transcription-PCR (qRT-PCR). Furthermore, the interaction
      between miR-17-5p and SMAD7 was observed. We found that in non-traumatic ON
      samples the level of mature miR-17-5p was significantly lower than that of OA
      samples (P=0.0002). By targeting SMAD7, miR-17-5p promoted nuclear translocation
      of beta-catenin, enhanced expression of COL1A1 and finally facilitated the
      proliferation and differentiation of HMSC-bm cells. We also demonstrated that
      restoring expression of SMAD7 in HMSC-bm cells partially reversed the function of
      miR-17-5p. Together, our data suggested a theory that dysfunction of a network
      containing miR-17-5p, SMAD7 and beta-catenin could contribute to ON pathogenesis.
      The present study prompts the potential clinical value of miR-17-5p in non
      traumatic ON. 

PMID- 25060768
TI  - An extreme value theory approach for the early detection of time clusters. A
      simulation-based assessment and an illustration to the surveillance of
      Salmonella.
AB  - We propose a new method that could be part of a warning system for the early
      detection of time clusters applied to public health surveillance data. This
      method is based on the extreme value theory (EVT). To any new count of a
      particular infection reported to a surveillance system, we associate a return
      period that corresponds to the time that we expect to be able to see again such a
      level. If such a level is reached, an alarm is generated. Although standard EVT
      is only defined in the context of continuous observations, our approach allows to
      handle the case of discrete observations occurring in the public health
      surveillance framework. Moreover, it applies without any assumption on the
      underlying unknown distribution function. The performance of our method is
      assessed on an extensive simulation study and is illustrated on real data from
      Salmonella surveillance in France.

PMID- 25060772
TI  - T3 levels in relation to prognostic factors in breast cancer: a population-based
      prospective cohort study.
AB  - BACKGROUND: The issue of a potential association between thyroid
      conditions/hormones and breast cancer has been studied extensively during the
      last decades but the results have been inconclusive and almost no studies have
      investigated breast cancer aggressiveness. We have previously found a positive
      association between prospectively measured levels of triiodothyronine (T3) and
      breast cancer incidence as well as breast cancer mortality. We now investigated
      prediagnostic T3 levels in relation to specific prognostic factors in breast
      cancer. METHODS: The Malmo Preventive Project is a population-based prospective
      cohort including 2185 women in whom T3 levels were measured at baseline. That is,
      total T3 levels were measured before a potential diagnosis of breast cancer. Mean
      follow-up was 23.3 years and 149 women in the study population were diagnosed
      with invasive breast cancer. Tumours were classified according to selected
      prognostic factors of breast cancer; i.e. grade, tumour size, lymph node
      metastasis, and hormonal receptor status. T3 was handled both as tertiles and as
      a continuous variable. A Cox's proportional hazards analysis yielded hazard
      ratios with 95% confidence intervals. All analyses were also restricted to
      postmenopausal women. RESULTS: Overall there was a statistically significant
      association between T3 and "all" breast cancers. The adjusted Hazard Ratio (HR)
      in the third tertile, as compared to the first, was (1.61:1.07-2.43). There was a
      statistically significant positive association between the third T3 tertile and
      large tumours, i.e. > 20 mm, (3.17:1.20-8.36) and the occurrence of lymph node
      metastases, (4.53:1.60-12.83). Other prognostic factors positively associated
      with T3 were negative oestrogen receptor (ER) status, (3.52:1.32-9.41) and
      negative progesterone receptor (PGR) status, (3.52:1.42-8.75). The analyses of T3
      as a continuous variable and analysis restricted to postmenopausal women,
      confirmed the results but also showed an association with smaller tumours and in
      postmenopausal women a contemporary association with negative lymph nodes.
      CONCLUSIONS: This prospective study of serum T3 levels in relation to breast
      cancer aggressiveness is the first of its kind. We found statistically
      significant positive associations between higher prediagnostic T3 levels and
      larger tumours, occurrence of lymph node metastases, and negative ER and PGR
      status.

PMID- 25060773
TI  - Next generation ligand binding assays-review of emerging real-time measurement
      technologies.
AB  - Over the last few years, numerous ligand binding assay technologies that utilize
      real-time measurement have been introduced; however, an assemblage and evaluation
      of these technologies has not previously been published. Herein, we describe six
      emerging real-time measurement technologies: MaverickTM, MX96 SPRTM, NanoDLSayTM,
      AMMP(r)/ViBE(r), SoPranoTM, and two Lab-on-a-Chip (LoC) microfluidic devices. The
      development stage gate of these technologies ranges from pre-commercial to
      commercially available. Due to the novelty, the application and utility of some
      of the technologies regarding bioanalysis are likely to evolve but it is our hope
      that this review will provide insight into the direction the development of real
      time measurement technologies is moving and the vision of those that are taking
      us there. Following the technology discussions, a comprehensive summary table is
      presented.

PMID- 25060774
TI  - High KLF4 level in normal tissue predicts poor survival in colorectal cancer
      patients.
AB  - BACKGROUND: Kruppel-like factor 4 (KLF4) is involved in many important cellular
      processes such as growth, development, differentiation, proliferation, and
      apoptosis. The purpose of this study was to determine the significance of KLF4 in
      both tumors and normal tissues of patients with colorectal cancer (CRC). METHODS:
      Between January 2003 and June 2005, 125 patients with CRC receiving treatment at
      the Yonsei Cancer Center were selected. We examined the mRNA level of the KLF4
      gene in primary CRC specimens and matched normal colon tissues using real-time RT
      PCR. Correlation of survival with clinicopathological parameters, including KLF4
      level, was investigated with univariate and multivariate analyses. RESULTS: CRC
      tissue had a significantly lower KLF4 level when compared with matched normal
      tissues (KLF4 in tumors: 2007 +/- 1531 copies/MUl, KLF4 in normal tissues: 6586
      +/- 2834 copies/MUl; P < 0.0001). However, there was a correlation between the
      KLF4 level in tumors and normal tissues. Patients with a high KLF4 level in
      matched normal tissues were more likely than those with a low KLF4 level to
      develop recurrence and had poorer overall survival (P = 0.005). Therefore, the
      KLF4 level in the normal tissue of individuals was associated with prognosis of
      individuals. CONCLUSIONS: Our data suggest that KLF4 mRNA expression level in
      normal tissues and tumors may be a useful prognostic marker in patients with CRC.

PMID- 25060775
TI  - Exercise intolerance, malnutrition, abnormal sweat chloride levels, and two CFTR
      mutations: is it cystic fibrosis?

PMID- 25060776
TI  - Isolation and characterization of a subtype C avian metapneumovirus circulating
      in Muscovy ducks in China.
AB  - Subtype C avian metapneumovirus (aMPV-C), is an important pathogen that can cause
      egg-drop and acute respiratory diseases in poultry. To date, aMPV-C infection has
      not been documented in Muscovy ducks in China. Here, we isolated and
      characterized an aMPV-C, designated S-01, which has caused severe respiratory
      disease and noticeable egg drop in Muscovy duck flocks in south China since 2010.
      Electron microscopy showed that the isolate was an enveloped virus exhibiting
      multiple morphologies with a diameter of 20-500 nm. The S-01 strain was able to
      produce a typical cytopathic effect (CPE) on Vero cells and cause death in 10- to
      11-day-old Muscovy duck embryos. In vivo infection of layer Muscovy ducks with
      the isolate resulted in typical clinical signs and pathological lesions similar
      to those seen in the original infected cases. We report the first complete
      genomic sequence of aMPV-C from Muscovy ducks. A phylogenetic analysis strongly
      suggested that the S-01 virus belongs to the aMPV-C family, sharing 92.3%-94.3%
      of nucleotide identity with that of aMPV-C, and was most closely related to the
      aMPV-C strains isolated from Muscovy ducks in France. The deduced eight main
      proteins (N, P, M, F, M2, SH, G and L) of the novel isolate shared higher
      identity with hMPV than with other aMPV (subtypes A, B and D). S-01 could bind a
      monoclonal antibody against the F protein of hMPV. Together, our results indicate
      that subtype-C aMPV has been circulating in Muscovy duck flocks in South China,
      and it is urgent for companies to develop new vaccines to control the spread of
      the virus in China.

PMID- 25060777
TI  - Self-assembling small molecules for the detection of important analytes.
AB  - Nano-materials formed by the self-assembly of small molecules are very promising
      for drug delivery, regenerative medicine, and detection of important analytes due
      to their unique properties, such as self-assembled multivalency,
      biocompatibility, and fast response to external stimuli. This tutorial review
      focuses on their applications in detection of important analytes. Self-assembling
      small molecules can show fast response to external stimuli. Therefore, the gel
      sol/sol-gel phase transitions of supramolecular hydrogels that can be easily
      identified by naked eyes have been applied for the detection of enzymes and
      enzyme-involving analytes. The supramolecular hydrogels can also provide semi-wet
      environments that can retain the activity of enzymes and recognition properties
      of molecular probes. Thus, they provide good platforms for the detection of many
      biologically and environmentally important analytes. Besides, self-assembling
      small molecules show big differences in fluorescence or the F-NMR signal between
      their self-assembled and un-assembled stages. Such small molecules can be
      rationally designed through the integration of fluorescent dyes or fluorine
      containing molecules in the self-assembling small molecules. Therefore, extensive
      recent research efforts have been made to explore their detection applications
      based on the dis-assembly triggered fluorescence/F-NMR signal turn on or the self
      assembly/aggregation induced fluorescence turn on. We believe that the research
      efforts made to this field will ultimately lead to the development of useful nano
      materials for detection applications. 

PMID- 25060778
TI  - Low treatment rates in patients meeting guideline criteria in diverse practice
      settings.
AB  - BACKGROUND AND AIMS: Data on usage of antiviral therapy and application of
      chronic hepatitis B (CHB) management guidelines in different settings are
      limited. Our goal is to evaluate the proportion of treatment-eligible patients by
      6-month follow-up and treatment rate among eligible patients by 12-month follow
      up in diverse settings. METHODS: In this retrospective cohort study, 1,976
      treatment-naive CHB patients were categorized as primary care physician (PCP)
      group if seen by community PCP (n = 329), gastroenterology (GI) group if seen by
      community gastroenterologists (n = 1,268), and hepatology group if seen by
      university hepatologists (n = 379). Treatment eligibility was based on the US
      Panel 2008 and American Association for the Study of Liver Diseases (AASLD) 2009
      guidelines. RESULTS: All groups had similar age, gender, and ethnic distribution.
      GI and hepatology groups had similar treatment eligibility rates by US Panel (53
      54 %) and AASLD guidelines (24-25 %). However, treatment rate was significantly
      higher in hepatology compared to GI group by the US Panel guideline (59 vs. 45 %,
      P = 0.001). PCP group had the lowest eligibility and treatment rates by both
      guidelines. Common reasons for non-treatment were perceived "normal" alanine
      aminotransferase, desire for further observation, and patient refusal. Male
      gender, age >50, and subspecialty care predicted treatment initiation in
      treatment-eligible patients. CONCLUSIONS: Less than half of treatment-eligible
      patients at primary care clinics received treatment. Community gastroenterology
      and university liver clinics treated about one-half to two-thirds of eligible
      patients. Patient and provider education should highlight treatment benefits and
      the new alanine aminotransferase upper limit of normal.

PMID- 25060779
TI  - Ceramide metabolism analysis in a model of binge drinking reveals both
      neuroprotective and toxic effects of ethanol.
AB  - Binge drinking is a common form of alcohol abuse that involves repeated rounds of
      intoxication followed by withdrawal. The episodic effects of binge drinking and
      withdrawal on brain resident cells are thought to contribute to neural remodeling
      and neurological damage. However, the molecular mechanisms for these
      neurodegenerative effects are not understood. Ethanol (EtOH) regulates the
      metabolism of ceramide, a highly bioactive lipid that is enriched in brain. We
      used a mouse model of binge drinking to determine the effects of EtOH
      intoxication and withdrawal on brain ceramide metabolism. Intoxication and acute
      alcohol withdrawal were each associated with distinct changes in ceramide
      regulatory genes and metabolic products. EtOH intoxication was accompanied by
      decreased concentrations of multiple ceramides, coincident with reductions in the
      expression of enzymes involved in the production of ceramides, and increased
      expression of ceramide-degrading enzymes. EtOH withdrawal was associated with
      specific increases in ceramide C16:0, C18:0, and C20:0 and increased expression
      of enzymes involved with ceramide production. These data suggest that EtOH
      intoxication may evoke a ceramide phenotype that is neuroprotective, whereas EtOH
      withdrawal results in a metabolic shift that increases the production of
      potentially toxic ceramide species.

PMID- 25060780
TI  - High genetic diversity and absence of founder effects in a worldwide aquatic
      invader.
AB  - The introduced oriental shrimp Palaemon macrodactylus has recently become
      widespread in temperate estuaries worldwide. However, this recent worldwide
      spread outside of its native range arises after a previous introduction to the US
      Pacific coast, where it was restricted for more than 30 years. Using a
      phylogeographic approach, the present work investigates the genetic history of
      the invasion of this decapod worldwide. Japan acted as the main native source
      area for worldwide introduced populations, but other native areas (likely South
      Korea and China) may act as source populations as well. The recently introduced
      European and NW Atlantic populations result from colonization from both Japan and
      an unknown area of the native range, although colonization from the NE Pacific
      could not be ruled out. Most introduced populations had higher haplotypic
      diversity than most native populations. P. macrodactylus has a strong potential
      to become one of the most widespread introduced species and may become the
      dominant estuarine shrimp in Europe. The ecological and economic consequences of
      this invasion remain to be thoroughly evaluated. 

PMID- 25060781
TI  - Hf-Nd isotopic variability in mineral dust from Chinese and Mongolian deserts:
      implications for sources and dispersal.
AB  - Mineral dust provenances are closely related to the orogenic processes which may
      have distinct Hf-Nd isotopic signatures. Here we report the clay-sized (<2 MUm)
      Hf-Nd isotope data from Asian dust sources to better constrain the source and
      transport dynamics of dust deposition in the North Pacific. Our results show that
      there is a more positive radiogenic Hf isotopic composition with clay-sized
      fractions than the corresponding bulk sample and a decoupling of the Hf-Nd
      couplets in the clay formation during the weathering process. The clay-sized Hf
      Nd isotopic compositions of the desert samples from the Sino-Korean-Tarim Craton
      (SKTC) are different from those of the Gobi and deserts from the Central Asian
      Orogeny Belt (CAOB) due to varying tectonic and weathering controls. The Hf-Nd
      isotopic compositions of dust in the North Pacific central province (NPC) match
      closely with those from the Taklimakan, Badain Jaran and adjacent Tengger
      deserts, implying that the NPC dust was mainly transported from these potential
      sources by the westerly jet. Our study indicates that dusts from the CAOB Gobi
      deserts either didn't arrive in NPC or were quantitatively insignificant, but
      they were likely transported to the North Pacific margin province (NPM) by East
      Asian winter monsoon.

PMID- 25060782
TI  - alpha-Fetoprotein and hepatocellular cancer recurrence: a paradigm of the chaos
      theory.

PMID- 25060783
TI  - An ultrasound biomicroscopy study after deep sclerectomy with supraciliary
      implant.
AB  - OBJECTIVE: To evaluate patients 24 months after deep sclerectomy (DE) with
      supraciliary implant, and identify any predictive success factors by examination
      with ultrasound biomicroscopy (UBM) MATERIAL AND METHODS: This study included 26
      eyes of 23 patients evaluated by UBM 24 months after a deep sclerectomy with a
      supraciliary hema implant. RESULTS: There was a significant reduction in
      intraocular pressure (IOP), changing from a preoperative mean of 25.6 +/- 6.4
      mmHg to a postoperative mean of 16.2 +/- 3.4 mmHg (P<.001). The number of
      preoperative glaucoma medications also decreased from 2.5 +/- 0.6 drugs per
      patient to 0.5 +/- 0.5 (P<.001). No change was observed in the best-corrected
      visual acuity. The anatomical characteristics of the surgical area, and its
      relationship with IOP were examined using UBM. There was no correlation between
      the level of IOP at the time of UBM and the horizontal (r=-.05: P=.71) and
      vertical diameter (r=-.1; P=.63), the height (r=.28; P=.25) and the volume of
      intrascleral space (r=-.08; P=.79), the thickness (r=-.07; P=.73) and the length
      (r=.39; P=.13) of trabeculo-Descemet's membrane (TDM), the presence of filtering
      bleb (P=.30) and the hypoechoic area in the supraciliary space (P=.24).
      CONCLUSIONS: The insertion of a hema implant in the supraciliary space is an
      effective and safe surgery for patients with open angle glaucoma (OAG). No
      predictive success factors for supraciliary implant were found using the UBM
      study.

PMID- 25060784
TI  - Translational implications of oxytocin-mediated social buffering following
      immobilization stress in female prairie voles.

PMID- 25060785
TI  - A drug to rob grief and anger of their sting and banish all painful memories.

PMID- 25060786
TI  - Testosterone, neural circuits, and male depression.

PMID- 25060787
TI  - Genetic diversity of Streptococcus suis isolated from three pig farms of China
      obtained by acquiring antibiotic resistance genes.
AB  - BACKGROUND: Acquiring antibiotic resistance genes may change an organism's
      genetic characteristics and the effect of antibiotics, resulting in a rapid
      transmission of microbial pathogens. The objectives of this experiment were to
      identify the features of Streptococcus suis (S. suis) isolated from three pig
      farms in China which are geographically isolated. RESULTS: Among the isolates,
      56.52% were sequence type 7 (ST7), followed by ST1 (26.09%), indicating that ST7
      prevails in China, as revealed by multi-locus sequence typing (MLST). Statistical
      analysis indicated an association between geography, sequence types and
      antibiotic resistance genotypes. 66.67% of the isolates in Sichuan province
      presented a (ermB(-) + mefA(-) + tetO(-) + tetM(-)) + ST7 type. The tetM(+) +ST7
      type was the most prevalent in Jiangsu province, whereas the strains from Hebei
      province had a phenotype ermB(+) +tetO(+) +ST1 (63.64%). Pulsed-field gel
      electrophoresis (PGFE) pattern A2 with 100% similarity reflected the clonal
      dissemination between Sichuan and Jiangsu provinces. Strains carrying or not
      carrying antibiotic resistance genes presented different PFGE patterns in Hebei
      province. CONCLUSION: ST7 is widespread in many regions of China and a clonal
      dissemination occurred between Sichuan and Jiangsu provinces in diseased pigs.
      However, ST1 strains with macrolide and tetracycline resistance (ermB(+) +tetO(+)
      +ST1) isolated from a farm in Hebei province demonstrated that the genetic
      diversity was contributed by horizontal acquiring of ermB and tetO carrying
      elements.

PMID- 25060788
TI  - Induction of lysosomal biogenesis in atherosclerotic macrophages can rescue lipid
      induced lysosomal dysfunction and downstream sequelae.
AB  - OBJECTIVE: Recent reports of a proatherogenic phenotype in mice with macrophage
      specific autophagy deficiency have renewed interest in the role of the autophagy
      lysosomal system in atherosclerosis. Lysosomes have the unique ability to process
      both exogenous material, including lipids and autophagy-derived cargo such as
      dysfunctional proteins/organelles. We aimed to understand the effects of an
      atherogenic lipid environment on macrophage lysosomes and to evaluate novel ways
      to modulate this system. APPROACH AND RESULTS: Using a variety of complementary
      techniques, we show that oxidized low-density lipoproteins and cholesterol
      crystals, commonly encountered lipid species in atherosclerosis, lead to profound
      lysosomal dysfunction in cultured macrophages. Disruptions in lysosomal pH,
      proteolytic capacity, membrane integrity, and morphology are readily seen. Using
      flow cytometry, we find that macrophages isolated from atherosclerotic plaques
      also display features of lysosome dysfunction. We then investigated whether
      enhancing lysosomal function can be beneficial. Transcription factor EB (TFEB) is
      the only known transcription factor that is a master regulator of lysosomal
      biogenesis although its role in macrophages has not been studied. Lysosomal
      stress induced by chloroquine or atherogenic lipids leads to TFEB nuclear
      translocation and activation of lysosomal and autophagy genes. TFEB
      overexpression in macrophages further augments this prodegradative response and
      rescues several deleterious effects seen with atherogenic lipid loading as
      evidenced by blunted lysosomal dysfunction, reduced secretion of the
      proinflammatory cytokine interleukin-1beta, enhanced cholesterol efflux, and
      decreased polyubiquitinated protein aggregation. CONCLUSIONS: Taken together,
      these data demonstrate that lysosomal function is markedly impaired in
      atherosclerosis and suggest that induction of a lysosomal biogenesis program in
      macrophages has antiatherogenic effects.

PMID- 25060790
TI  - Reciprocal effects of systemic inflammation and brain natriuretic peptide on
      adiponectin biosynthesis in adipose tissue of patients with ischemic heart
      disease.
AB  - OBJECTIVE: To explore the role of systemic inflammation in the regulation of
      adiponectin levels in patients with ischemic heart disease. APPROACH AND RESULTS:
      In a cross-sectional study of 575 subjects, serum adiponectin was compared
      between healthy subjects, patients with coronary artery disease with
      no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin
      expression and release from femoral, subcutaneous and thoracic adipose tissue was
      determined in 258 additional patients with coronary artery bypass grafting.
      Responsiveness of the various human adipose tissue depots to interleukin-6, tumor
      necrosis factor-alpha, and brain natriuretic peptide (BNP) was examined by using
      ex vivo models of human fat. The effects of inducible low-grade inflammation were
      tested by using the model of Salmonella typhi vaccine-induced inflammation in
      healthy individuals. In the cross-sectional study, HF strikingly increased
      adiponectin levels. Plasma BNP was the strongest predictor of circulating
      adiponectin and its release from all adipose tissue depots in patients with
      coronary artery bypass grafting, even in the absence of HF. Femoral AT was the
      depot with the least macrophages infiltration and the largest adipocyte cell size
      and the only responsive to systemic and ex vivo proinflammatory stimulation
      (effect reversible by BNP). Low-grade inflammation reduced circulating
      adiponectin levels, while circulating BNP remained unchanged. CONCLUSIONS: This
      study demonstrates the regional variability in the responsiveness of human
      adipose tissue to systemic inflammation and suggests that BNP (not systemic
      inflammation) is the main driver of circulating adiponectin in patients with
      advanced atherosclerosis even in the absence of HF. Any interpretation of
      circulating adiponectin as a biomarker should take into account the underlying
      disease state, background inflammation, and BNP levels.

PMID- 25060789
TI  - Diversity is in my veins: role of bone morphogenetic protein signaling during
      venous morphogenesis in zebrafish illustrates the heterogeneity within
      endothelial cells.
AB  - Endothelial cells are a highly diverse group of cells which display distinct
      cellular responses to exogenous stimuli. Although the aptly named vascular
      endothelial growth factor-A signaling pathway is hailed as the most important
      signaling input for endothelial cells, additional factors also participate in
      regulating diverse aspects of endothelial behaviors and functions. Given this
      heterogeneity, these additional factors seem to play a critical role in creating
      a custom-tailored environment to regulate behaviors and functions of distinct
      subgroups of endothelial cells. For instance, molecular cues that modulate
      morphogenesis of arterial vascular beds can be distinct from those that govern
      morphogenesis of venous vascular beds. Recently, we have found that bone
      morphogenetic protein signaling selectively promotes angiogenesis from venous
      vascular beds without eliciting similar responses from arterial vascular beds in
      zebrafish, indicating that bone morphogenetic protein signaling functions as a
      context-dependent regulator during vascular morphogenesis. In this review, we
      will provide an overview of the molecular mechanisms that underlie proangiogenic
      effects of bone morphogenetic protein signaling on venous vascular beds in the
      context of endothelial heterogeneity and suggest a more comprehensive picture of
      the molecular mechanisms of vascular morphogenesis during development. 

PMID- 25060791
TI  - Lower Apo A-I and lower HDL-C levels are associated with higher intermediate
      CD14++CD16+ monocyte counts that predict cardiovascular events in chronic kidney
      disease.
AB  - OBJECTIVE: Patients with chronic kidney disease (CKD) display impaired
      cholesterol efflux capacity and elevated CD14(++)CD16(+) monocyte counts. In
      mice, dysfunctional cholesterol efflux causes monocytosis. It is unknown whether
      cholesterol efflux capacity and monocyte subsets are associated in CKD. APPROACH
      AND RESULTS: In 438 patients with CKD, mediators of cholesterol efflux capacity
      (high-density lipoprotein cholesterol/apolipoprotein A-I) and monocyte subsets
      were analyzed as predictors of cardiovascular events. Monocyte subset-specific
      intracellular lipid content, CD36, CD68, and ABCA1 were measured in a subgroup.
      Experimentally, we analyzed subset-specific cholesterol efflux capacity and
      response to oxidized low-density lipoprotein cholesterol stimulation in CKD.
      Epidemiologically, both low Apo-I and low high-density lipoprotein cholesterol
      were associated with high CD14(++)CD16(+) monocyte counts in linear regression
      analyses (apolipoprotein A-I: beta=-0.171; P<0.001; high-density lipoprotein
      cholesterol: beta=-0.138; P=0.005), but not with counts of other monocyte
      subsets. In contrast to apolipoprotein A-I or high-density lipoprotein
      cholesterol, higher CD14(++)CD16(+) monocyte counts independently predicted
      cardiovascular events (hazard ratio per increase of 1 cell/MUL: 1.011 [1.003
      1.020]; P=0.007). Experimentally, CD14(++)CD16(+) monocytes demonstrated
      preferential lipid accumulation, high CD36, CD68, and low ABCA1 expression and,
      consequently, displayed low cholesterol efflux capacity, avid oxidized low
      density lipoprotein cholesterol uptake, and potent intracellular interleukin-6,
      interleukin-1beta, and tumor necrosis factor-alpha production. CONCLUSIONS: Taken
      together, mediators of cholesterol efflux are associated with CD14(++)CD16(+)
      monocyte counts, which independently predict adverse outcome in CKD.

PMID- 25060792
TI  - Olive oil polyphenols enhance high-density lipoprotein function in humans: a
      randomized controlled trial.
AB  - OBJECTIVE: Olive oil polyphenols have shown beneficial properties against
      cardiovascular risk factors. Their consumption has been associated with higher
      cholesterol content in high-density lipoproteins (HDL). However, data on
      polyphenol effects on HDL quality are scarce. We, therefore, assessed whether
      polyphenol-rich olive oil consumption could enhance the HDL main function, its
      cholesterol efflux capacity, and some of its quality-related properties, such HDL
      polyphenol content, size, and composition. APPROACH AND RESULTS: A randomized,
      crossover, controlled trial with 47 healthy European male volunteers was
      performed. Participants ingested 25 mL/d of polyphenol-poor (2.7 mg/kg) or
      polyphenol-rich (366 mg/kg) raw olive oil in 3-week intervention periods,
      preceded by 2-week washout periods. HDL cholesterol efflux capacity significantly
      improved after polyphenol-rich intervention versus the polyphenol-poor one
      (+3.05% and -2.34%, respectively; P=0.042). Incorporation of olive oil polyphenol
      biological metabolites to HDL, as well as large HDL (HDL2) levels, was higher
      after the polyphenol-rich olive oil intervention, compared with the polyphenol
      poor one. Small HDL (HDL3) levels decreased, the HDL core became triglyceride
      poor, and HDL fluidity increased after the polyphenol-rich intervention.
      CONCLUSIONS: Olive oil polyphenols promote the main HDL antiatherogenic function,
      its cholesterol efflux capacity. These polyphenols increased HDL size, promoted a
      greater HDL stability reflected as a triglyceride-poor core, and enhanced the HDL
      oxidative status, through an increase in the olive oil polyphenol metabolites
      content in the lipoprotein. Our results provide for the first time a first-level
      evidence of an enhancement in HDL function by polyphenol-rich olive oil.

PMID- 25060793
TI  - Impact of phospholipid transfer protein on nascent high-density lipoprotein
      formation and remodeling.
AB  - OBJECTIVE: Phospholipid transfer protein (PLTP), which binds phospholipids and
      facilitates their transfer between lipoproteins in plasma, plays a key role in
      lipoprotein remodeling, but its influence on nascent high-density lipoprotein
      (HDL) formation is not known. The effect of PLTP overexpression on apolipoprotein
      A-I (apoA-I) lipidation by primary mouse hepatocytes was investigated. APPROACH
      AND RESULTS: Overexpression of PLTP through an adenoviral vector markedly
      affected the amount and size of lipidated apoA-I species that were produced in
      hepatocytes in a dose-dependent manner, ultimately generating particles that were
      <7.1 nm but larger than lipid-free apoA-I. These <7.1-nm small particles
      generated in the presence of overexpressed PLTP were incorporated into mature HDL
      particles more rapidly than apoA-I both in vivo and in vitro and were less
      rapidly cleared from mouse plasma than lipid-free apoA-I. The <7.1-nm particles
      promoted both cellular cholesterol and phospholipid efflux in an ATP-binding
      cassette transporter A1-dependent manner, similar to apoA-I in the presence of
      PLTP. Lipid-free apoA-I had a greater efflux capacity in the presence of PLTP
      than in the absence of PLTP, suggesting that PLTP may promote ATP-binding
      cassette transporter A1-mediated cholesterol and phospholipid efflux. These
      results indicate that PLTP alters nascent HDL formation by modulating the
      lipidated species and by promoting the initial process of apoA-I lipidation.
      CONCLUSIONS: Our findings suggest that PLTP exerts significant effects on apoA-I
      lipidation and nascent HDL biogenesis in hepatocytes by promoting ATP-binding
      cassette transporter A1-mediated lipid efflux and the remodeling of nascent HDL
      particles.

PMID- 25060795
TI  - Thyroid hormones and coronary artery calcification in euthyroid men and women.
AB  - OBJECTIVE: Overt and subclinical hypothyroidism are risk factors for
      atherosclerosis. It is unclear whether thyroid hormone levels within the normal
      range are also associated with atherosclerosis measured by coronary artery
      calcium (CAC). APPROACH AND RESULTS: We conducted a cross-sectional study of 41
      403 apparently healthy young and middle-aged men and women with normal thyroid
      hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating
      hormone levels were measured by electrochemiluminescent immunoassay. CAC score
      was measured by multidetector computed tomography. The multivariable adjusted CAC
      ratios comparing the highest versus the lowest quartile of thyroid hormones were
      0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin,
      0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64
      0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds
      ratios for detectable CAC (CAC >0) comparing the highest versus the lowest
      quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001)
      for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free
      triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid
      stimulating hormone. CONCLUSIONS: In a large cohort of apparently healthy young
      and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid
      stimulating hormone were associated with a higher prevalence of subclinical
      coronary artery disease and with a greater degree of coronary calcification.

PMID- 25060794
TI  - Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk.
AB  - OBJECTIVE: CXCL12 encodes stromal cell-derived factor 1alpha (SDF-1), which binds
      to the receptor encoded by CXCR4. Variation at the CXCL12 locus is associated
      with coronary artery disease and endothelial progenitor cell numbers, whereas
      variation at the CXCR4 locus is associated with leukocyte telomere length, which
      has been shown to be associated with coronary artery disease. Therefore, we
      examined the relationships of plasma SDF-1 levels to cardiovascular disease (CVD)
      related outcomes, risk factors, leukocyte telomere length, and endothelial
      progenitor cells. APPROACH AND RESULTS: SDF-1 was measured in 3359 Framingham
      Heart Study participants. We used Cox regression to examine relationships of SDF
      1 to new-onset CVD, myocardial infarction, heart failure, and all-cause
      mortality; we used linear regression to evaluate associations of SDF-1 with risk
      factors, leukocyte telomere length, and CD34+ cell phenotypes. In multivariable
      models, higher SDF-1 levels were associated with older age, lower levels of high
      density lipoprotein-cholesterol and cigarette smoking. Higher SDF-1 levels were
      associated with lower CD34+ cell frequency (P=0.02) but not with leukocyte
      telomere length. During follow-up (median, 9.3 years), there were 263 new-onset
      CVD events, 160 myocardial infarctions, 200 heart failure events, and 385 deaths.
      After adjusting for clinical risk factors, SDF-1 levels were associated with
      heart failure (P=0.04) and all-cause mortality (P=0.003) but not with CVD
      (P=0.39) or myocardial infarction (P=0.10). The association of SDF-1 levels with
      myocardial infarction was attenuated after adjustment for high-density
      lipoprotein-cholesterol. CONCLUSIONS: After adjusting for traditional CVD risk
      factors, SDF-1 is associated with heart failure and all-cause mortality risk.
      Additional studies are needed to determine whether measurement of SDF-1 levels
      has clinical use.

PMID- 25060796
TI  - Osteopontin-CD44v6 interaction mediates calcium deposition via phospho-Akt in
      valve interstitial cells from patients with noncalcified aortic valve sclerosis.
AB  - OBJECTIVE: The activation of valve interstitial cells (VICs) toward an osteogenic
      phenotype characterizes aortic valve sclerosis, the early asymptomatic phase of
      calcific aortic valve disease. Osteopontin is a phosphorylated acidic
      glycoprotein that accumulates within the aortic leaflets and labels VIC
      activation even in noncalcified asymptomatic patients. Despite this, osteopontin
      protects VICs against in vitro calcification. Here, we hypothesize that the
      specific interaction of osteopontin with CD44v6, and the related intracellular
      pathway, prevents calcium deposition in human-derived VICs from patients with
      aortic valve sclerosis. APPROACH AND RESULTS: On informed consent, 23 patients
      and 4 controls were enrolled through the cardiac surgery and heart transplant
      programs. Human aortic valves and VICs were tested for osteogenic
      transdifferentiation, ex vivo and in vitro. Osteopontin-CD44 interaction was
      analyzed using proximity ligation assay and the signaling pathways investigated.
      A murine model based on angiotensin II infusion was used to mimic early
      pathological remodeling of the aortic valves. We report osteopontin-CD44
      functional interaction as a hallmark of early stages of calcific aortic valve
      disease. We demonstrated that osteopontin-CD44 interaction mediates calcium
      deposition via phospho-Akt in VICs from patients with noncalcified aortic valve
      sclerosis. Finally, microdissection analysis of murine valves shows increased
      cusp thickness in angiotensin II-treated mice versus saline infused along with
      colocalization of osteopontin and CD44 as seen in human lesions. CONCLUSIONS:
      Here, we unveil a specific protein-protein association and intracellular
      signaling mechanisms of osteopontin. Understanding the molecular mechanisms of
      early VIC activation and calcium deposition in asymptomatic stage of calcific
      aortic valve disease could open new prospective for diagnosis and therapeutic
      intervention.

PMID- 25060797
TI  - Thin-cap fibroatheroma rupture is associated with a fine interplay of shear and
      wall stress.
AB  - In this review, we summarized the effect of mechanical factors (shear and wall
      stress) on thin-cap fibroatheroma formation and rupture. To make this review
      understandable for a biology-oriented audience, we start with detailed
      definitions of relevant mechanical metrics. We then describe how biomechanics has
      supported histopathologic efforts to understand the basis of plaque rupture. In
      addition to plaque rupture, biomechanics also contributes toward the progression
      of thin-cap fibroatheroma through a multitude of reported mechanobiological
      mechanisms. We thus propose a new mechanism whereby both shear stress and wall
      stress interact to create thin-cap fibroatheromas. Specifically, when regions of
      certain blood flow and wall mechanical stimuli coincide, they synergistically
      create inflammation within the cellular environment that can lead to thin-cap
      fibroatheroma rupture. A consequence of this postulate is that local shear stress
      is not sufficient to cause rupture, but it must coincide with regions of local
      tissue stiffening and stress concentrations that can occur during plaque
      progression. Because such changes to the wall mechanics occur over a micrometer
      scale, high spatial resolution imaging techniques will be necessary to evaluate
      this hypothesis and ultimately predict plaque rupture in a clinical environment. 

PMID- 25060798
TI  - One-and-a-half ventricle repair as a surgical alternative to Fontan revision in
      an adult.
AB  - We report a case of a young man with hypoplastic right ventricle, who presented
      with recurrent untreatable arrhythmias after a Bjork Fontan procedure in infancy.
      He underwent one-and-a-half ventricle repair as an alternative surgery to Fontan
      revision.

PMID- 25060799
TI  - MRI of placental adhesive disorder.
AB  - Placental adhesive disorder (PAD) is a serious pregnancy complication that occurs
      when the chorionic villi invade the myometrium. Placenta praevia and prior
      caesarean section are the two important risk factors. PAD is classified on the
      basis of the depth of myometrial invasion (placenta accreta, placenta increta and
      placenta percreta). MRI is the preferred image modality for pre-natal diagnosis
      of PAD and as complementary technique when ultrasonography is inconclusive.
      Imaging findings that are helpful for the diagnosis include dark intraplacental
      bands, direct invasion of adjacent structures by placental tissue, interruption
      of normal trilayered myometrium and uterine bulging. Clinicians should be aware
      of imaging features of PAD to facilitate optimal patient management. 

PMID- 25060800
TI  - Inflammation and arrhythmias: potential mechanisms and clinical implications.
AB  - Inflammation is a pathological condition known since ancient times. Recent
      discoveries of inflammatory markers have given new insights into the role of
      inflammation in the pathogenesis of arrhythmias. This article reviews global data
      on possible correlations between inflammation - acute or chronic - and cardiac
      arrhythmias. The authors discuss the role of inflammation in patients with
      supraventricular and ventricular arrhythmias. Collected data support the
      hypothesis that the inflammatory process may be an important factor in cardiac
      rhythm disturbances. 

PMID- 25060801
TI  - First Polish outbreak of Clostridium difficile ribotype 027 infections among
      dialysis patients.
AB  - This report describes an outbreak of Clostridium difficile infection (CDI) in a
      nephrology ward in 2012, caused by the fluoroquinolone- and clindamycin-resistant
      polymerase chain reaction (PCR) ribotype 027 strains. An increase in the number
      of cases of diarrhoea was noted among patients hospitalised between 26 November
      2012 and 17 December 2012 in a hospital in North Poland. Eight patients were on
      haemodialysis in the outpatient dialysis facility, while one patient was
      receiving peritoneal dialysis. The 027 strain could be detected in eight
      haemodialysis patients. One strain, isolated from the patient receiving
      peritoneal dialysis, belonged to PCR ribotype 001. In this study, we documented
      the first outbreak of CDI caused by a fluoroquinolone-resistant (FQR) C.
      difficile PCR ribotype 027 strain in Polish dialysis patients. 

PMID- 25060803
TI  - Topical corticosteroid reduces inflammation without compromising the efficacy of
      photodynamic therapy for actinic keratoses: a randomized clinical trial.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an effective and established treatment
      for actinic keratoses (AK) and nonmelanoma skin cancer. The main side-effects of
      PDT are post-treatment erythema and oedema, and pain during illumination. Severe
      erythema after PDT enhances the down time associated with the treatment.
      OBJECTIVES: To evaluate in a randomized intraindividual study whether use of a
      topical corticosteroid just before and just after PDT would reduce treatment
      induced erythema compared with conventional PDT. METHODS: Twenty-two patients
      with multiple AKs in the face and scalp were treated with methyl aminolaevulinate
      PDT in two symmetrical areas. One area was randomized to superpotent
      corticosteroid (clobetasol propionate) before and just after PDT. Objective and
      visual erythema, protoporphyrin IX (PpIX) fluorescence and pain were evaluated.
      RESULTS: Topical corticosteroid significantly reduced PDT-induced erythema (P =
      0.012). The complete lesion response rate 3 months after PDT, and PpIX
      fluorescence prior to illumination did not differ significantly between the two
      treated areas. CONCLUSIONS: Superpotent corticosteroid before and just after PDT
      reduced the erythema 24 h after treatment of multiple AKs on the face and scalp.
      The use of topical corticosteroid did not affect the efficacy of PDT and may be
      an easy way to make PDT treatment of large visible areas more acceptable.

PMID- 25060804
TI  - The sweat matrix: a new perspective for drugs analysis.

PMID- 25060802
TI  - Best practice in healthcare environment decontamination.
AB  - There is now strong evidence that surface contamination is linked to healthcare
      associated infections (HCAIs). Cleaning and disinfection should be sufficient to
      decrease the microbial bioburden from surfaces in healthcare settings, and,
      overall, help in decreasing infections. It is, however, not necessarily the case.
      Evidence suggests that there is a link between educational interventions and a
      reduction in infections. To improve the overall efficacy and appropriate usage of
      disinfectants, manufacturers need to engage with the end users in providing clear
      claim information and product usage instructions. This review provides a clear
      analysis of the scientific evidence supporting the role of surfaces in HCAIs and
      the role of education in decreasing such infections. It also examines the debate
      opposing the use of cleaning versus disinfection in healthcare settings. 

PMID- 25060805
TI  - Long-term survivorship clinics led by primary care physicians within the cancer
      center may be a good option for coordinated survivorship care.

PMID- 25060806
TI  - Aflatoxins contamination in Pakistani brown rice: a comparison of TLC, HPLC, LC
      MS/MS and ELISA techniques.
AB  - Advancement in the field of analytical food-chemistry has explored various
      experimental techniques for aflatoxins (AFs) quantification. The present study
      was aimed to compare four different techniques; thin-layer chromatography (TLC),
      high-performance liquid chromatography (HPLC), liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) for the
      analysis of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) in brown rice
      (n = 120) being collected from Karachi, Pakistan. All the four assays provide
      precised, accurate and comparable results. However, some differences were
      observed. For instance, TLC, HPLC and LC-MS/MS methodologies offered the
      advantage of the quantification of individual toxins in contrast to ELISA
      technique. The contamination ranges of AFB1/AFB2 as determined by TLC, HPLC and
      LC-MS/MS were 1.18-9.97/0.59-1.52, 0.16-10.54/0.26-1.35 and 0.11-10.88/0.38-1.48
      ug/kg, respectively. However, AFG1 and AFG2 were not detected in any tested
      samples. Furthermore, owing to low-detection limit and sensitivity, HPLC and LC
      MS/MS methodologies have identified greater number of contaminated samples in
      comparison to TLC and ELISA techniques. The overall average results of total AFs
      as provided by HPLC (3.79 ug/kg) and LC-MS/MS (3.89 ug/kg) were found higher in
      comparison to TLC (3.68 ug/kg) and ELISA (3.70 ug/kg). On the basis of achieved
      results, it was concluded that TLC, HPLC, LC-MS/MS and ELISA techniques are
      valuable tool for the quantification of AFs in cereals and grains. Furthermore,
      HPLC and LC-MS/MS techniques offer an added advantage for the detection of AFs in
      diminutive levels.

PMID- 25060807
TI  - CD49d Treg cells with high suppressive capacity are remarkably less efficient on
      activated CD45RA- than on naive CD45RA+ Teff cells.
AB  - BACKGROUND: Impairment of regulatory T cells (Tregs) in common autoimmune
      diseases seems likely. However, the extent of Treg deficiency (number, function)
      or differential susceptibility of T effector cells (Teffs) to suppression is not
      completely understood. We hypothesize that even in healthy individuals both cell
      populations are heterogeneous and differ in their suppressive capability and
      their susceptibility to suppression. MATERIAL AND METHODS: Lymphocytes were
      enriched by MACS for CD4(+)CD25(+) Tregs or CD4(+)CD25(-) Teffs. After
      multicolour staining (anti-CD25, anti-CD127, anti-CD49d or anti-CD45RA) highly
      purified Treg and Teff subpopulations were collected by FACS. Functional capacity
      of Tregs or suppressive susceptibility of Teffs was analyzed in an in vitro
      assay. RESULTS: When CD4(+)CD25(high)CD127(-/low) CD49d(-) Tregs were tested on
      naive CD4(+)CD127(+)CD25(-)CD45RA(+) Teffs (93.8 %) suppression was almost
      complete, while the suppressive capacity of CD4(+)CD25(high)CD127(-/low) CD49d(+)
      Tregs was significantly less (71.8 %). Suppressive activity was low when
      CD4(+)CD25(high)CD127(-/low) CD49d(+) Tregs were analyzed on CD4(+)CD127(+)CD25(
      )CD45RA(-) Teffs (48.7%). CONCLUSION: Although CD49d(+) Tregs are functional, the
      suppressive capacity is significantly lower compared to CD49d(-) Tregs. CD45RA(+)
      Teffs can be completely suppressed, while CD45RA(-) Teffs display relative
      resistance. Phenotypic and functional heterogeneity of Tregs as well as Teffs has
      to be considered when analyzing deficiencies in immune regulation.

PMID- 25060808
TI  - [Facial edema in a 39-year-old woman].

PMID- 25060809
TI  - Long-term workforce participation patterns following head and neck cancer.
AB  - PURPOSE: This analysis describes the long-term workforce participation patterns
      of individuals diagnosed with head and neck cancer (HNC). METHODS: Survivors of
      HNC (ICD10 C00-C14, C32) diagnosed at least 8 months previously were identified
      from the National Cancer Registry Ireland and sent a survey including questions
      about working arrangements before and since diagnosis. Descriptive statistics and
      multivariate logistic regression were used to examine the factors that influence
      workforce participation at 0, 1 and 5 years after diagnosis. RESULTS: Two hundred
      sixty-four individuals employed at the time of diagnosis responded to the survey,
      an average 6 years post-diagnosis. Seventy-seven percent took time off work after
      diagnosis, with a mean work absence of 9 months (range 0-65 months). Fifty-two
      percent of participants reduced their working hours (mean reduction 15 h/week).
      The odds of workforce participation following HNC were increased by not being
      eligible for free medical care (OR 2.61, 95% CI 1.15-5.94), having lip, mouth or
      salivary gland cancer (compared to cancer of the pharynx or cancer of the larynx,
      OR 2.79, 1.20-6.46), being self-employed (OR 2.01, 1.07-3.80), having private
      health insurance (OR 2.06, 1.11-3.85) and not receiving chemotherapy (OR 2.82,
      1.31-6.06). After 5 years, only the effect of medical card remained (i.e.,
      medical insurance) (OR 4.03, 1.69-9.62). CONCLUSIONS: Workforce participation
      patterns after HNC are complex and are influenced by cancer, treatment and
      employment factors. IMPLICATIONS FOR CANCER SURVIVORS: Patients should be
      informed of the potential impacts of HNC on workforce participation, and
      clinicians, policy makers and employers should be aware of these potential longer
      term effects and related variables.

PMID- 25060810
TI  - Genomic complexity and plasticity ensure Pseudomonas success.

PMID- 25060811
TI  - International comparison of common risk factors of preterm birth between the U.S.
      and Canada, using PRAMS and MES (2005-2006).
AB  - Preterm birth (PTB) is a leading cause of newborn deaths and morbidities. The
      pregnancy risk assessment monitoring system (PRAMS) from the U.S., and the
      maternity experiences survey (MES) from Canada, which was modeled from PRAMS,
      were used to examine between-country differences in risk factors of preterm
      birth. The adjusted risk ratio and population attributable fraction (PAF) were
      calculated for modifiable and semi-modifiable risk factors of PTB, and all
      measures were compared between the U.S. and Canada. PTB was defined here as a
      live singleton birth between 28 and 37 completed weeks gestation (using the
      clinical gestational age estimate) where the baby was living with the mother at
      the time of the survey. The PTB risk was 7.6 % (SE = 0.2) in the U.S. and 4.9 %
      (SE = 0.3) in Canada. The a priori high risk category of factors was almost
      always more prevalent in the U.S. than Canada, suggesting broad social
      differences, but individually most of these differences were not associated with
      PTB. The underlying risk of PTB was generally higher in the U.S. in both the
      higher risk and referent categories, and the risk ratios for most risk factors
      were similar between the countries. The primary exception was for recurrence of
      PTB, where the risk ratio (RR) and PAF were much higher in Canada. We observed
      between-country differences in both the prevalence of risk factors and the
      adjusted RR. Further between-country comparisons may lead to important inferences
      as to the influence of modifiable risk factors contributing to PTB. 

PMID- 25060812
TI  - Interaction of mTOR and Erk1/2 signaling to regulate oligodendrocyte
      differentiation.
AB  - A multitude of factors regulate oligodendrocyte differentiation and
      remyelination, and to elucidate the mechanisms underlying this process, we
      analyzed the interactions of known signaling pathways involved in these
      processes. Previous work from our lab and others shows that Akt, mTOR, and Erk
      1/2 are major signaling pathways regulating oligodendrocyte differentiation and
      myelination in vitro and in vivo. However, the relative contribution of the
      different pathways has been difficult to establish because the impact of
      inhibiting one pathway in in vitro cell culture models or in vivo may alter
      signaling through the other pathway. These studies were undertaken to clarify the
      interactions between these major pathways and understand more specifically the
      crosstalk between them. Oligodendrocyte differentiation in vitro required Akt,
      mTOR, and Erk 1/2 signaling, as inhibition of Akt, mTOR, or Erk 1/2 resulted in a
      significant decrease of myelin basic protein mRNA and protein expression.
      Interestingly, while inhibition of the Erk1/2 pathway had little impact on
      Akt/mTOR signaling, inhibition of the Akt/mTOR pathways significantly increased
      Erk1/2 signaling, although not enough to overcome the loss of Akt/mTOR signaling
      in the regulation of oligodendrocyte differentiation. Furthermore, such crosstalk
      was also noted in an in vivo context, after mTOR inhibition by rapamycin
      treatment of perinatal pups. GLIA 2014;62:2096-2109. 

PMID- 25060813
TI  - SMARCA4-mutated atypical teratoid/rhabdoid tumors are associated with inherited
      germline alterations and poor prognosis.

PMID- 25060814
TI  - Nanoparticles and pop-off technique for electron microscopy: a known technique
      for a new purpose.
AB  - Because of the size of the nanoparticles, their detection and exact anatomical
      localization in tissue samples are very difficult. Consequently, suitable methods
      are needed to prove their presence, especially co-localized to histological
      lesions. Therefore, the aim of this study was to investigate whether
      nanoparticles were detectable in specimens after reprocessing samples from glass
      slides using the pop-off technique. Tissue slides containing agglomerates of
      titanium dioxide nanoparticles already visible on a light microscopic level and
      amorphous silicium dioxide (SiO2) particles not observable in tissue slides were
      reprocessed. Furthermore, cytospots of bronchoalveolar lavage acquired from rats
      that previously inhaled carbon nanotubes were used. After reprocessing the
      samples, they were investigated using transmission electron microscopy. In all
      the reprocessed samples, the respective nanoparticles were detectable. Even the
      light microscopically invisible amorphous SiO2 particles were observed as
      electron dense structures. Titanium and silicium were additionally confirmed in
      the respective nanoparticles by energy-dispersive X-ray spectroscopy (EDX). In
      summary, the pop-off technique represents a fast and easy way to detect
      nanoparticles in histological sections. This enables further characterization of
      these particles by additional techniques such as EDX, and their direct
      correlation with light microscopic lesions at exactly the same location is
      investigated.

PMID- 25060815
TI  - The radiographic effects of the scarf bunionectomy on rearfoot alignment.
AB  - STATEMENT OF PURPOSE: Excessive pronation of the rearfoot has been implicated as
      a destabilizing force in the progression of hallux abducto valgus. Although the
      scarf bunionectomy has been shown to effectively correct the intermetatarsal
      angle associated with hallux valgus deformity, its effect on the rearfoot has yet
      to be established. The purpose of this case series is to demonstrate the effect
      of the scarf bunionectomy on rearfoot alignment. METHODOLOGY: Medical records
      were reviewed to isolate patients who underwent unilateral or bilateral scarf
      bunionectomies (with or without akin osteotomy) who had complete medical records,
      follow-up of at least 12 months, and met the inclusion/exclusion criteria.
      Preoperative and postoperative radiographic measurements were analyzed at various
      postoperative time intervals. Standard deviations and statistical significance
      was obtained. RESULTS: One hundred feet (71 patients) were included in this
      analysis. The long-term results of this study highlighted the scarf osteotomy's
      ability to affect the medial longitudinal arch by decreasing the intermetatarsal
      angle and lateral talar-first metatarsal angle. The talar declination and
      calcaneal inclination angle were not significantly altered with the scarf
      bunionectomy. CONCLUSION: This case series demonstrates that the scarf
      bunionectomy had significant effect on radiographic alignment of the bunion
      deformity and medial longitudinal arch over time. However, its effect on the
      rearfoot position was not statistically significant. LEVELS OF EVIDENCE:
      Therapeutic, Level IV: Case Series.

PMID- 25060816
TI  - Transcriptome sequencing of different narrow-leafed lupin tissue types provides a
      comprehensive uni-gene assembly and extensive gene-based molecular markers.
AB  - Narrow-leafed lupin (NLL; Lupinus angustifolius L.) is an important grain legume
      crop that is valuable for sustainable farming and is becoming recognized as a
      human health food. NLL breeding is directed at improving grain production,
      disease resistance, drought tolerance and health benefits. However, genetic and
      genomic studies have been hindered by a lack of extensive genomic resources for
      the species. Here, the generation, de novo assembly and annotation of
      transcriptome datasets derived from five different NLL tissue types of the
      reference accession cv. Tanjil are described. The Tanjil transcriptome was
      compared to transcriptomes of an early domesticated cv. Unicrop, a wild accession
      P27255, as well as accession 83A:476, together being the founding parents of two
      recombinant inbred line (RIL) populations. In silico predictions for
      transcriptome-derived gene-based length and SNP polymorphic markers were
      conducted and corroborated using a survey assembly sequence for NLL cv. Tanjil.
      This yielded extensive indel and SNP polymorphic markers for the two RIL
      populations. A total of 335 transcriptome-derived markers and 66 BAC-end sequence
      derived markers were evaluated, and 275 polymorphic markers were selected to
      genotype the reference NLL 83A:476 * P27255 RIL population. This significantly
      improved the completeness, marker density and quality of the reference NLL
      genetic map. 

PMID- 25060817
TI  - Curcumin analogues with high activity for inhibiting human prostate cancer cell
      growth and androgen receptor activation.
AB  - The androgen receptor (AR) has a critical role in prostate cancer development and
      progression. Several curcumin analogues (A10, B10, C10, E10 and F10) with
      different linker groups were investigated for their effects in human prostate
      cancer CWR-22Rv1 and LNCaP cell lines. The ability of these compounds to inhibit
      testosterone (TT)- or dihydrotestosterone (DHT)-induced AR activity was
      determined by an AR-linked luciferase assay and by TT- or DHT-induced expression
      of prostate specific antigen. Compounds F10 and E10 had stronger inhibitory
      effects on the growth of cultured CWR-22Rv1 and LNCaP cell lines, and they also
      had enhanced stimulatory effects on apoptosis compared with curcumin and other
      curcumin analogues (A10, B10, C10) in CWR-22Rv1 cells. E10 and F10 were more
      potent inhibitors of AR activity than curcumin, A10 and B10. The higher
      activities of E10 and F10 may be correlated with a heteroatom linker. The results
      indicate that one of the potential mechanisms for the anticancer effect of the
      curcumin analogues was inhibition of AR pathways in human prostate cancer cells.

PMID- 25060818
TI  - Delayed clavulanic acid-induced anaphylaxis in a patient undergoing bariatric
      surgery.

PMID- 25060819
TI  - Impact of exhaled nitric oxide measurements on treatment decisions in an asthma
      specialty clinic.
AB  - BACKGROUND: Asthma management in an outpatient setting is best accomplished by
      clinical evaluation coupled with spirometry and symptom evaluation, but these
      assessments do not provide information about airway inflammation. Exhaled nitric
      oxide (fraction of exhaled nitric oxide [FeNO]) measures T-helper cell type 2
      mediated airway inflammation and may be a useful adjunct in asthma management.
      OBJECTIVE: To determine whether the use of FeNO in the specialist management of
      asthma results in more effective and cost-effective treatment decisions. METHODS:
      Fifty subjects 7 to 60 years old with established asthma participated in this
      observational study. Subjects were evaluated by clinical examination, spirometry,
      and symptom assessment using the Asthma Control Test, and clinicians estimated
      airway inflammation and made treatment decisions based on these assessments.
      Then, FeNO was measured, and changes in therapy based on FeNO levels were
      documented. The estimated cost impact of using FeNO was calculated presuming
      ongoing FeNO use in patient management. RESULTS: Without FeNO, the clinician's
      assessment of airway inflammation was incorrectly classified in 50% of subjects.
      FeNO results substantially altered treatment decisions in more than one third of
      subjects, notably medication augmentation in 10 (20%) and medication decreases in
      8 (16%). Use of FeNO in addition to standard of care was estimated to save $629
      per subject per year. CONCLUSION: Measurement of FeNO augments routine clinical
      assessment of asthma by measuring airway inflammation. Knowledge of FeNO affects
      medication treatment decisions to augment or decrease pharmacotherapy, which has
      important long-term asthma management implications, most notably the potential to
      lower the costs and morbidity associated with asthma exacerbation. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT01729247.

PMID- 25060820
TI  - Cardiac implanted electronic device-related infective endocarditis: clinical
      features, management, and outcomes of 80 consecutive patients.
AB  - BACKGROUND: The use of cardiac implantable electronic devices (CIEDs) has
      expanded dramatically over the past decade, but net clinical benefit has been
      curtailed by increasing infectious complications. In particular, CIED-related
      infectious endocarditis (IE) is a serious condition with significant morbidity
      and mortality. METHODS: We performed a single-center, retrospective study between
      July 2006 and February 2011 with CIED-related IE, defined by either lead
      vegetations detected on echocardiography or by fulfilling Duke criteria for
      definite endocarditis. Clinical parameters and outcomes were detailed by
      electronic medical record review and vital status was confirmed by the Social
      Security Death Index. RESULTS: Eighty patients (median age 67, interquartile
      range 56-75, 58 M/22 F) were diagnosed with CIED-related IE. Overall mortality
      was 36% with a median time to death of 95 days from presentation. Over half (52%)
      of the deaths were infection related with a median time to death of 29 days.
      Multivariate analysis showed methicillin-resistant Staphylococcus aureus (MRSA)
      infection (odds ratio [OR] 0.158; 95% confidence interval [CI], 0.047-0.534; P =
      .003) and concomitant valve endocarditis (OR 0.141, CI 0.041-0.491, P = .002)
      independently predicted mortality. CONCLUSION: In this contemporary series, all
      cause mortality in patients with CIED-related IE was high with a short time to
      death from onset of infection. MRSA and concomitant valve infection were the most
      powerful independent predictors of mortality.

PMID- 25060821
TI  - [CNS tumors in childhood].

PMID- 25060822
TI  - [Anterior knee pain of traumatic origin : Case report on a rare differential
      diagnosis].

PMID- 25060823
TI  - Printable planar lightwave circuits with a high refractive index.
AB  - We report a novel nanofabrication method to fabricate printable integrated
      circuits with a high refractive index working in the visible wavelength range.
      The printable planar ligthwave circuits are directly imprinted by ultra-violet
      nanoimprinting into functional TiO2-based resist on the top of planar waveguide
      core films. The printed photonic circuits are composed of several elementary
      components including ridge waveguides, light splitters and digital planar
      holograms. Multi-mode ridge waveguides with propagation losses around 40 dB cm(
      1) at 660 nm wavelength, and, on-chip demultiplexers operated in the visible
      range with 100 channels and a spectral channel spacing around 0.35 nm are
      successfully demonstrated. 

PMID- 25060824
TI  - Accumulation of the Type IV prepilin triggers degradation of SecY and YidC and
      inhibits synthesis of Photosystem II proteins in the cyanobacterium Synechocystis
      PCC 6803.
AB  - Type IV pilins are bacterial proteins that are small in size but have a broad
      range of functions, including motility, transformation competence and secretion.
      Although pilins vary in sequence, they possess a characteristic signal peptide
      that has to be removed by the prepilin peptidase PilD during pilin maturation. We
      generated a pilD (slr1120) null mutant of the cyanobacterium Synechocystis 6803
      that accumulates an unprocessed form of the major pilin PilA1 (pPilA1) and its
      non-glycosylated derivative (NpPilA1). Notably, the pilD strain had aberrant
      membrane ultrastructure and did not grow photoautotrophically because the
      synthesis of Photosystem II subunits was abolished. However, other membrane
      components such as Photosystem I and ATP synthase were synthesized at levels
      comparable to the control strain. Proliferation of the pilD strain was rescued by
      elimination of the pilA1 gene, demonstrating that PilA1 prepilin inhibited the
      synthesis of Photosystem II. Furthermore, NpPilA1 co-immunoprecipitated with the
      SecY translocase and the YidC insertase, and both of these essential translocon
      components were degraded in the mutant. We propose that unprocessed prepilins
      inactivate an identical pool of translocons that function in the synthesis of
      both pilins and the core subunits of Photosystem II. 

PMID- 25060825
TI  - Health-related quality of life 14 years after preoperative short-term
      radiotherapy and total mesorectal excision for rectal cancer: report of a
      multicenter randomised trial.
AB  - BACKGROUND: Preoperative short-term radiotherapy (PRT) in combination with total
      mesorectal excision (TME) has shown to improve local control in rectal cancer
      treatment, however without a survival benefit and at the cost of increased
      morbidity. The current study investigates the long-term health-related quality of
      life (HRQL) of patients 14 years after treatment in the Dutch TME trial. METHODS:
      In the TME trial (1996-1999) 1530 Dutch patients with rectal cancer were treated
      with TME and randomly assigned to PRT (5 * 5 Gy). In 2012 HRQL was evaluated in
      surviving patients (n=606) using a questionnaire combining EORTC QLQ-C30, EORTC
      QLQ-CR29 and additional questions. FINDINGS: Results were obtained from 478
      patients (82%), with a median follow up of 14 years. PRT+TME patients without
      stoma reported more faecal leakage and higher stool frequency, resulting in
      increased need of pads. Furthermore, irradiated males reported more erection
      problems. However, radiotherapy did not have negative effects on overall
      functioning. Compared with Dutch population, patients in both treatment arms
      reported a small decrease in overall functioning and males reported less sexual
      activity, interest and enjoyment and more erection difficulties. Irradiated
      females reported more vaginal dryness and more pain at intercourse compared with
      Dutch population. INTERPRETATION: Long-term HRQL evaluation shows that treatment
      related symptoms are still present 14 years after treatment for rectal cancer.
      Radiotherapy increased bowel dysfunction in patients without stoma. Compared with
      the Dutch population, both groups reported increased sexual dysfunction. Despite
      these treatment-related symptoms, there was no difference in overall functioning
      and global health between TME and PRT+TME.

PMID- 25060826
TI  - Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate
      tumour regression.
AB  - Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique
      tool to activate drugs within a neoplastic mass due to their property to home and
      engraft into tumours. In particular, MSC expressing the cytosine
      deaminase::uracil phosphoribosyltransferase (CD-MSC) have been previously
      demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks
      to their ability to convert the non-toxic 5-fluorocytosine into the
      antineoplastic 5-fluorouracil. Since both the immune system and the tumour
      microenvironment play a crucial role in directing cancer progression, in order to
      advance towards clinical applications, we tested the therapeutic potential of
      this approach on animal models that develop autochthonous prostate cancer and
      preserve an intact immune system. As cell vectors, we employed adipose-tissue and
      bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour
      tropism were verified in vitro and ex-vivo before starting the preclinical
      studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour
      progression. We demonstrated that intravenous injections of CD-MSC cells,
      followed by intraperitoneal administration of 5-fluorocytosine, caused tumour
      regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model,
      which develops aggressive and spontaneous prostate cancer. These results add new
      insights to the therapeutic potential of specifically engineered MSC in prostate
      cancer disease. 

PMID- 25060828
TI  - Linkage analysis and exome sequencing identify a novel mutation in KCTD7 in
      patients with progressive myoclonus epilepsy with ataxia.
AB  - Epilepsy affects approximately 1% of the world's population. Genetic factors and
      acquired etiologies, as well as a range of environmental triggers, together
      contribute to epileptogenesis. We have identified a family with three daughters
      affected with progressive myoclonus epilepsy with ataxia. Clinical details of the
      onset and progression of the neurologic presentation, epileptic seizures, and the
      natural history of progression over a 10-year period are described. Using
      autozygosity genetic mapping, we identified a high likelihood homozygous region
      on chromosome 7p12.1-7q11.22. We subsequently applied whole-exome sequencing and
      employed a rare variant prioritization analysis within the homozygous region. We
      identified p.Tyr276Cys in the potassium channel tetramerization domain-containing
      seven gene, KCTD7, which is expressed predominantly in the brain. Mutations in
      this gene have been implicated previously in epileptic phenotypes due to
      disturbances in potassium channel conductance. Pathogenicity of the mutation was
      supported by bioinformatic predictive analyses and variant cosegregation within
      the family. Further biologic validation is necessary to fully characterize the
      pathogenic mechanisms that explain the phenotypic causes of epilepsy with ataxia
      in these patients. 

PMID- 25060829
TI  - What is the quality of economic evaluations of non-drug therapies? A systematic
      review and critical appraisal of economic evaluations of radiotherapy for cancer.
AB  - BACKGROUND: Breast, cervical and colorectal cancers are the three most frequent
      cancers in women, while lung, prostate and colorectal cancers are the most
      frequent in men. Much attention has been given to the economic evaluation of
      pharmaceuticals for treatment of cancer by the National Institute for Health and
      Care Excellence (NICE) in the UK and similar authorities internationally, while
      economic analysis developed for other types of anti-cancer interventions,
      including radiotherapy and surgery, are less common. OBJECTIVES: Our objective
      was to review methods used in published cost-effectiveness studies evaluating
      radiotherapy for breast, cervical, colorectal, head and neck and prostate cancer,
      and to compare the economic evaluation methods applied with those defined in the
      guidelines used by the NICE technology appraisal programme. METHODS: A systematic
      search of seven databases (MEDLINE, EMBASE, CDSR, NHSEED, HTA, DARE, EconLit) as
      well as research registers, the NICE website and conference proceedings was
      conducted in July 2012. Only economic evaluations of radiotherapy interventions
      in individuals diagnosed with cancer that included quality-adjusted life-years
      (QALYs) or life-years (LYs) were included. Included studies were appraised on the
      basis of satisfying essential, preferred and UK-specific methods requirements,
      building on the NICE Reference Case for economic evaluations and on other methods
      guidelines. RESULTS: A total of 29 studies satisfied the inclusion criteria
      (breast 14, colorectal 2, prostate 10, cervical 0, head and neck 3). Only two
      studies were conducted in the UK (13 in the USA). Among essential methods
      criteria, the main issue was that only three (10%) of the studies used clinical
      effectiveness estimates identified through systematic review of the literature.
      Similarly, only eight (28%) studies sourced health-related quality-of-life data
      directly from patients with the condition of interest. Other essential criteria
      (e.g. clear description of comparators, patient group indication and appropriate
      time horizon) were generally fulfilled, while most of the UK-specific
      requirements were not met. CONCLUSION: Based on this review there is a dearth of
      up-to-date, robust evidence on the cost effectiveness of radiotherapy in cancer
      suitable to support decision making in the UK. Studies selected did not fully
      satisfy essential method standards currently recommended by NICE.

PMID- 25060830
TI  - EXOGEN ultrasound bone healing system for long bone fractures with non-union or
      delayed healing: a NICE medical technology guidance.
AB  - A routine part of the process for developing National Institute for Health and
      Care Excellence (NICE) medical technologies guidance is a submission of clinical
      and economic evidence by the technology manufacturer. The Birmingham and Brunel
      Consortium External Assessment Centre (EAC; a consortium of the University of
      Birmingham and Brunel University) independently appraised the submission on the
      EXOGEN bone healing system for long bone fractures with non-union or delayed
      healing. This article is an overview of the original evidence submitted, the
      EAC's findings, and the final NICE guidance issued. 

PMID- 25060831
TI  - Narcissism: is parenting style to blame, or is there X-chromosome involvement?

PMID- 25060832
TI  - In action or inaction? Social approach-avoidance tendencies in major depression.
AB  - In depression, approach deficits often impair everyday social functioning, but
      empirical findings on performance-based measurements of approach-avoidance
      behavior remain conflicting. To investigate action tendencies in patients with
      depression, the current study used an explicit version of the Approach-Avoidance
      Task (AAT). In this task, participants responded to emotional faces by either
      pulling a joystick toward (approach) or pushing it away from themselves (avoid).
      Reaction times to happy and angry expressions with direct and averted gaze were
      assessed in 30 patients with major depressive disorder and 20 matched healthy
      controls. In contrast to healthy individuals, depressed patients did not show
      approach-avoidance tendencies, i.e., there was no dominant behavioral tendency
      and they reacted to happy and angry expressions likewise. These results indicate
      that behavioral adjustments to different emotional expressions, gaze directions
      or motivational demands were lacking in depression. Crucially, this distinguishes
      depressed patients not only from healthy individuals, but also from other
      clinical populations that demonstrate aberrant approach-avoidance tendencies,
      e.g., patients with social anxiety or psychopathy. As responding flexibly to
      different social signals is integral to social interactions, the absence of any
      social motivational tendencies seems maladaptive, but may also provide
      opportunities for modifying action tendencies in a therapeutic context. 

PMID- 25060833
TI  - Efficacy of a multimodal treatment for disruptive behavior disorders in children
      and adolescents: focus on internalizing problems.
AB  - Disruptive Behavior Disorders (DBDs) are among the most common reasons for youth
      referrals to mental health clinics. Aim of this study is to compare short and
      medium term efficacy of a multimodal treatment program (MTP), compared to
      community care (treatment-as-usual, TAU). The sample included 135 youths with
      DBDs (113 males, age range 9-15 years, mean age 12+/-2.5 years) were assigned
      either to a MTP (n=64), or addressed to community care for a TAU (n=71). Outcome
      measures were the Child Behaviour Checklist (CBCL) and the Children's Global
      Assessment Scale (C-GAS). All subjects were assessed at the baseline (T0), after
      1-year treatment (T1) and after a 2-year follow-up (T2). Compared with patients
      receiving TAU, youths in the MTP showed, both at T1 and T2, significantly lower
      scores on CBCL Externalizing Scale, Internalizing Scale, Anxious/Depressed,
      Social Problems, and Aggressive Behavior, and higher scores at the C-GAS.
      Improvement in Internalizing Scales was particularly evident, with a shift from
      the clinical to the non-clinical range. Rate of use of mental health services and
      scholastic failure were reduced in the MTP. It is suggested that the improvement
      of the Internalizing symptoms is a crucial component of the therapeutic process
      in this MTP.

PMID- 25060834
TI  - Reproductive clonality in protozoan pathogens--truth or artefact?
AB  - The debate around the frequency and importance of genetic exchange in parasitic
      protozoa is now several decades old. Recently, fresh assertions have been made
      that predominant clonal evolution explains the population structures of several
      key protozoan pathogens. Here, we present an alternative perspective. On the
      assumption that much apparent clonality may be an artefact of inadequate sampling
      and study design, we review current research to define why sex might be so
      difficult to detect in protozoan parasite populations. In doing so, we contrast
      laboratory models of genetic exchange in parasitic protozoa with natural patterns
      of genetic diversity and consider the fitness advantage of sex at different
      evolutionary scales. We discuss approaches to improve the accuracy of efforts to
      characterize genetic exchange in the field. We also examine the implications of
      the first population genomic studies for the debate around sex and clonality in
      parasitic protozoa and discuss caveats for the future. 

PMID- 25060835
TI  - [Vascular assessment in stroke codes: role of computed tomography angiography].
AB  - Advances in imaging studies for acute ischemic stroke are largely due to the
      development of new efficacious treatments carried out in the acute phase.
      Together with computed tomography (CT) perfusion studies, CT angiography
      facilitates the selection of patients who are likely to benefit from appropriate
      early treatment. CT angiography plays an important role in the workup for acute
      ischemic stroke because it makes it possible to confirm vascular occlusion,
      assess the collateral circulation, and obtain an arterial map that is very useful
      for planning endovascular treatment. In this review about CT angiography, we
      discuss the main technical characteristics, emphasizing the usefulness of the
      technique in making the right diagnosis and improving treatment strategies. 

PMID- 25060836
TI  - Synergy of bone marrow transplantation and curcumin ensue protective effects at
      early onset of diabetes in mice.
AB  - BACKGROUND: The aim of this study was to investigate the early onset effects of
      diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells,
      organs (pancreas and kidney) damage and the reversal effect of diabetes by
      combinatorial treatment of curcumin and bone marrow transplantation in
      streptozotocin (STZ) induced diabetic mice. METHODS: In the present study,
      Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2
      * 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight).
      Effect of diabetes on the different organs was studied by H&E, Western blotting
      and immunofluorescence using vascular endothelial growth factor (VEGF),
      platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and
      Caspase-3 antibodies. RESULTS: The effect of diabetes results in the reduction of
      the total cell number and viability of the bone marrow cells, organ degeneration
      and lower VEGF/PECAM expression. However, transplantation with normal bone marrow
      cells significantly reduced the blood glucose levels (above normal range) and
      initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin
      treatment further reduced the blood glucose level (near normal); and accelerated
      the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase
      expression level in the organs. Curcumin also had a protective role against the
      glucotoxicity test performed on the bone marrow cells. CONCLUSION: This study
      suggests that bone marrow transplantation and curcumin administration is an
      effective treatment in reversing the early onset effects of diabetes via the
      VEGF/PECAM signaling pathway.

PMID- 25060837
TI  - Atomistic insight into the catalytic mechanism of glycosyltransferases by
      combined quantum mechanics/molecular mechanics (QM/MM) methods.
AB  - Glycosyltransferases catalyze the formation of glycosidic bonds by assisting the
      transfer of a sugar residue from donors to specific acceptor molecules. Although
      structural and kinetic data have provided insight into mechanistic strategies
      employed by these enzymes, molecular modeling studies are essential for the
      understanding of glycosyltransferase catalyzed reactions at the atomistic level.
      For such modeling, combined quantum mechanics/molecular mechanics (QM/MM) methods
      have emerged as crucial. These methods allow the modeling of enzymatic reactions
      by using quantum mechanical methods for the calculation of the electronic
      structure of the active site models and treating the remaining enzyme environment
      by faster molecular mechanics methods. Herein, the application of QM/MM methods
      to glycosyltransferase catalyzed reactions is reviewed, and the insight from
      modeling of glycosyl transfer into the mechanisms and transition states
      structures of both inverting and retaining glycosyltransferases are discussed. 

PMID- 25060838
TI  - Enzymatic synthesis using glycoside phosphorylases.
AB  - Carbohydrate phosphorylases are readily accessible but under-explored catalysts
      for glycoside synthesis. Their use of accessible and relatively stable sugar
      phosphates as donor substrates underlies their potential. A wide range of these
      enzymes has been reported of late, displaying a range of preferences for sugar
      donors, acceptors and glycosidic linkages. This has allowed this class of enzymes
      to be used in the synthesis of diverse carbohydrate structures, including at the
      industrial scale. As more phosphorylase enzymes are discovered, access to further
      difficult to synthesise glycosides will be enabled. Herein we review reported
      phosphorylase enzymes and the glycoside products that they have been used to
      synthesise. 

PMID- 25060840
TI  - Phenological models to predict the main flowering phases of olive (Olea europaea
      L.) along a latitudinal and longitudinal gradient across the Mediterranean
      region.
AB  - The aim of the present study was to develop pheno-meteorological models to
      explain and forecast the main olive flowering phenological phases within the
      Mediterranean basin, across a latitudinal and longitudinal gradient that includes
      Tunisia, Spain, and Italy. To analyze the aerobiological sampling points, study
      periods from 13 years (1999-2011) to 19 years (1993-2011) were used. The
      forecasting models were constructed using partial least-squares regression,
      considering both the flowering start and full-flowering dates as dependent
      variables. The percentages of variance explained by the full-flowering models
      (mean 84 %) were greater than those explained by the flowering start models (mean
      77 %). Moreover, given the time lag from the North African areas to the central
      Mediterranean areas in the main olive flowering dates, the regional full
      flowering predictive models are proposed as the most useful to improve the
      knowledge of the influence of climate on the olive tree floral phenology. The
      meteorological parameters related to the previous autumn and both the winter and
      the spring seasons, and above all the temperatures, regulate the reproductive
      phenology of olive trees in the Mediterranean area. The mean anticipation of
      flowering start and full flowering for the future period from 2081 to 2100 was
      estimated at 10 and 12 days, respectively. One question can be raised: Will the
      olive trees located in the warmest areas be northward displaced or will they be
      able to adapt their physiology in response to the higher temperatures? The
      present study can be considered as an approach to design more detailed future
      bioclimate research.

PMID- 25060839
TI  - Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in
      buprenorphine-maintained heroin users.
AB  - In spite of the clinical utility of buprenorphine, parenteral abuse of this
      medication has been reported in several laboratory investigations and in the real
      world. Studies have demonstrated lower abuse liability of the
      buprenorphine/naloxone combination relative to buprenorphine alone. However,
      clinical research has not yet examined the utility of the combined formulation to
      deter intranasal use in a buprenorphine-maintained population. Heroin-using
      volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on
      each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each
      maintenance dose, participants completed laboratory sessions during which the
      reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16
      mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo,
      heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone
      typically produced increases in positive subjective effects and the 8 mg dose was
      self-administered above the level of placebo. The addition of naloxone dose
      dependently reduced positive subjective effects and increased aversive effects.
      No buprenorphine/naloxone combination dose was self-administered significantly
      more than placebo. These data suggest that within a buprenorphine-dependent
      population, intranasal buprenorphine/naloxone has reduced abuse potential in
      comparison to buprenorphine alone. These data strongly argue in favor of
      buprenorphine/naloxone rather than buprenorphine alone as the more reasonable
      option for managing the risk of buprenorphine misuse.

PMID- 25060841
TI  - Apelin and G212A apelin receptor gene polymorphism in obese and diabese youth.
AB  - OBJECTIVE: The apelinergic system has been previously described to participate in
      fluid homeostasis, cardiac contractility, blood pressure and neo-vascularization.
      The role of apelin in obesity and glucose metabolism has also lately gained
      interest; however, it still remains obscure. This study aimed to assess serum
      apelin levels in obese youngsters and to investigate any possible association
      with the G212A polymorphism of the apelin receptor (APLNR) gene. METHODS: Ninety
      obese individuals and 90 matched for age and gender lean controls were included.
      Anthropometric measurements, data of glucose metabolism, including an oral
      glucose tolerance test, and serum apelin levels were obtained. The presence of
      the G212A polymorphism of the APLNR gene was also analyzed in the obese group.
      RESULTS: Obese participants had significantly lower serum apelin levels as
      compared with controls (P = 0.011). After being grouped according to their status
      of glucose metabolism, only obese subjects with impaired glucose metabolism
      (diabese) exhibited lower apelin levels as compared with controls. The presence
      of the G212A polymorphism did not differ from the HapMap-reported frequencies in
      Caucasians (GG = 53.3%/GA = 38.9%/AlphaAlpha = 7.8% vs. GG = 46.9%/GA =
      39.8%/AlphaAlpha = 13.3%, P = 0.232). The GG and GA obese subgroups had
      significantly lower apelin levels as compared with the AA group (P = 0.013 and P
      = 0.016, respectively). CONCLUSION: Obese (especially diabese) youngsters
      demonstrated lower serum apelin levels; the G212A polymorphism of the APLNR gene
      was found to exert a favourable effect on circulating apelin levels in childhood
      obesity.

PMID- 25060842
TI  - Histone H3 dynamics in plant cell cycle and development.
AB  - Chromatin is a macromolecular complex where DNA associates with histone proteins
      and a variety of non-histone proteins. Among the 4 histone types present in
      nucleosomes, histone H3 is encoded by a large number of genes in most eukaryotic
      species and is the histone that contains the largest variety of potential post
      translational modifications in the N-terminal amino acid residues. In addition to
      centromeric histone H3, 2 major types of histone H3 exist, namely the canonical
      H3.1 and the variant H3.3. In this article, we review the most recent
      observations on the distinctive features of plant H3 proteins in terms of their
      expression and dynamics during the cell cycle and at various developmental
      stages. We also include a discussion on the histone H3 chaperones that actively
      participate in H3 deposition, in particular CAF-1, HIRA and ASF1, and on the
      putative plant homologs of human ATRX and DEK chaperones. Accumulating evidence
      confirms that the balanced deposition of H3.1 and H3.3 is of primary relevance
      for cell differentiation during plant organogenesis.

PMID- 25060843
TI  - Oxygen saturation measurements of the retinal vasculature in treated asymmetrical
      primary open-angle glaucoma using hyperspectral imaging.
AB  - PURPOSE: To determine whether there are differences in retinal vascular oxygen
      saturation measurements, estimated using a hyperspectral fundus camera, between
      normal eyes and treated eyes of subjects with asymmetrical primary open-angle
      glaucoma (POAG). METHODS: A noninvasive hyperspectral fundus camera was used to
      acquire spectral images of the retina at wavelengths between 556 and 650 nm in 2
      nm increments. In total, 14 normal eyes and both eyes of 11 treated POAG subjects
      were imaged and analyzed using algorithms that use the spectral variation of the
      optical densities of blood vessels to estimate the oxygen saturation of blood
      within the retinal vasculature. In the treated POAG group, each of the eyes were
      categorized, based on the mean deviation of the Humphrey visual-field analyzer
      result, as either more-advanced or less-advanced, glaucomatous eyes. Unpaired t
      tests (two-tailed) with Welch's correction were used to compare the mean oxygen
      saturation between the normal subjects and the treated POAG subgroups. RESULTS:
      In less-advanced and more-advanced-treated POAG eyes, mean retinal venular oxygen
      saturations (48.2+/-21.6% and 42.6+/-18.8%, respectively) were significantly
      higher than in normal eyes (27.9+/-9.9%; P=0.03 and 0.01, respectively).
      Arteriolar oxygen saturation was not significantly different between normal eyes
      and treated POAG eyes. CONCLUSIONS: The increased oxygen saturation of the
      retinal venules in advanced-treated POAG eyes may indicate reduced metabolic
      consumption of oxygen in the inner retinal tissues.

PMID- 25060844
TI  - Response to Dr Soleimani.

PMID- 25060845
TI  - Intra-orbital gas following sutureless small-gauge (23-gauge) vitrectomy
      masquerading as orbital cellulitis.

PMID- 25060846
TI  - Urrets-Zavalia syndrome as a complication of ocular hypotonia due to intravenous
      cidofovir treatment.

PMID- 25060847
TI  - Pulsed vs continuous light accelerated corneal collagen crosslinking: in vivo
      qualitative investigation by confocal microscopy and corneal OCT.
AB  - PURPOSE: To assess qualitative corneal changes and penetration of pulsed and
      continuous light accelerated crosslinking by in vivo confocal microscopy and
      corneal OCT. METHODS: A total of 20 patients affected from progressive
      keratoconus were enrolled in the study. Ten eyes of 10 patients underwent an
      epithelium-off pulsed-light accelerated corneal collagen crosslinking (PL-ACXL)
      by the KXL UV-A source (Avedro Inc.) with 8 min (1 s on/1 s off) of UV-A exposure
      at 30 mW/cm(2) and energy dose of 7.2 J/cm(2); 10 eyes of 10 patients underwent
      an epithelium-off continuous-light accelerated corneal collagen crosslinking (CL
      ACXL) at 30 mW/cm(2) for 4 min. Riboflavin 0.1% dextran-free plus hydroxyl-propyl
      methylcellulose solution (VibeX Rapid, Avedro Inc.) was used for a 10-min corneal
      soaking. Treated eyes were examined by in vivo scanning laser confocal analysis
      and spectral anterior segment OCT at 1, 3, and 6 months. RESULTS: Epithelial
      stratification and nerves regeneration improved in time, being complete at month
      6 in both groups without endothelial damage. Keratocyte apoptosis in PL-ACXL was
      estimated at a mean depth of ~200 MUm, whereas an uneven demarcation line was
      detectable by confocal microscopy at a mean depth of 160 MUm in CL-ACXL.
      CONCLUSION: In vivo confocal microscopy and corneal OCT allowed a precise
      qualitative analysis of the cornea after epithelium-off PL-ACXL and CL-ACXL
      treatments. Apoptotic effect was higher in pulsed than in continuous light
      treatments, exceeding 200 MUm in corneal stroma. According to different
      morphological data, the clinical efficacy of ACXL needs to be determined in a
      long-term follow-up and large cohort of patients.

PMID- 25060849
TI  - Sterile postoperative endophthalmitis following HOYA IOL insertion.

PMID- 25060848
TI  - Intraoperative testing of opening and closing pressure predicts risk of low
      intraocular pressure after Ahmed glaucoma valve implantation.
AB  - PURPOSE: The aim of this study was to assess whether intraoperative testing of
      silicone Ahmed glaucoma valves (AGVs) would identify valves with an increased
      risk of low postoperative intraocular pressure (IOP). METHODS: In 30 consecutive
      cases of glaucoma surgery with AGV implantation, after priming the AGV, we
      intraoperatively measured the opening pressure A, closing pressure B, and re
      opening pressure C using the active infusion pump of a phako-machine. IOP was
      checked postoperatively on the same day. Low IOP was defined as <5 mm Hg.
      Intraoperatively measured pressure characteristics of the valve function were
      analysed for their ability to predict postoperative IOP outcomes. RESULTS:
      Opening A, closing B, and re-opening C pressures (mean, (SD)) were 18.4 (5.1),
      8.3 (4.7), and 11.7 (4.8)mm Hg, respectively. Ten patients (33.3%) had low IOP.
      An opening pressure of <=18 mm Hg predicted low postoperative IOP with a
      sensitivity (10/10) of 100% (95% CI, 69.2-100) and a specificity (13/20) of 65.0%
      (95% CI, 40.8-84.6). CONCLUSIONS: AGVs have a high variability of opening,
      closing, and re-opening pressures. An opening pressure of <=18 mm Hg, a closing
      pressure of <=10 mm Hg, or a re-opening pressure of <=11 mm Hg identified all
      patients with low postoperative IOP.

PMID- 25060850
TI  - A binocular iPad treatment for amblyopic children.
AB  - PURPOSE: Monocular amblyopia treatment (patching or penalization) does not always
      result in 6/6 vision and amblyopia often recurs. As amblyopia arises from
      abnormal binocular visual experience, we evaluated the effectiveness of a novel
      home-based binocular amblyopia treatment. METHODS: Children (4-12 y) wore
      anaglyphic glasses to play binocular games on an iPad platform for 4 h/w for 4
      weeks. The first 25 children were assigned to sham games and then 50 children to
      binocular games. Children in the binocular group had the option of participating
      for an additional 4 weeks. Compliance was monitored with calendars and tracking
      fellow eye contrast settings. About half of the children in each group were also
      treated with patching at a different time of day. Best-corrected visual acuity,
      suppression, and stereoacuity were measured at baseline, at the 4- and 8-week
      outcome visits, and 3 months after cessation of treatment. RESULTS: Mean (+/-SE)
      visual acuity improved in the binocular group from 0.47+/-0.03 logMAR at baseline
      to 0.39+/-0.03 logMAR at 4 weeks (P<0.001); there was no significant change for
      the sham group. The effect of binocular games on visual acuity did not differ for
      children who were patched vs those who were not. The median stereoacuity remained
      unchanged in both groups. An additional 4 weeks of treatment did not yield
      additional visual acuity improvement. Visual acuity improvements were maintained
      for 3 months after the cessation of treatment. CONCLUSIONS: Binocular iPad
      treatment rapidly improved visual acuity, and visual acuity was stable for at
      least 3 months following the cessation of treatment.

PMID- 25060851
TI  - Femtosecond-assisted intrastromal corneal cross-linking for early and moderate
      keratoconus.

PMID- 25060852
TI  - What would an environmentally sustainable reproductive technology industry look
      like?
AB  - Through the use of assisted reproductive technologies (ARTs), multiple children
      are born adding to worldwide carbon emissions. Evaluating the ethics of offering
      reproductive services against its overall harm to the environment makes
      unregulated ARTs unjustified, yet the ART business can move towards
      sustainability as a part of the larger green bioethics movement. By integrating
      ecological ethos into the ART industry, climate change can be mitigated and the
      conversation about consumption can become a broader public discourse. Although
      the impact of naturally made children on the environment is undeniable, I will
      focus on the ART industry as an anthropogenic source of carbon emissions which
      lead to climate change. The ART industry is an often overlooked source of
      environmental degradation and decidedly different from natural reproduction as
      fertility centres provide a service for a fee and therefore can be subject to
      economic, policy and bioethical scrutiny. In this article, I will provide a brief
      background on the current state of human-driven climate change before suggesting
      two conservationist strategies that can be employed in the ART business. First,
      endorsing a carbon capping programme that limits the carbon emissions of ART
      businesses will be proposed. Second, I will recommend that policymakers eliminate
      funded ARTs for those who are not biologically infertile. I will conclude the
      article by urging policymakers and all those concerned with climate change to
      consider the effects of the reproductive technologies industry in light of
      climate change and move towards sustainability. 

PMID- 25060853
TI  - Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one
      pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine
      alkaloids.
AB  - Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been
      designed as substrates for a one-pot, two-step multi-bond-forming process leading
      to the general preparation of aminoindenes and amino-substituted 1,4
      dihydronaphthalenes. The synthetic utility of the privileged structures formed
      from this one-pot process was demonstrated with the total synthesis of four
      oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine,
      oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction,
      catalyzed using the Hermann-Beller palladacycle was used to effect the key step
      during the synthesis of the natural products. 

PMID- 25060854
TI  - Explaining fullerene dispersion by using micellar solutions.
AB  - An effective computational strategy to describe the dispersion of C60 by
      surfactants is presented. The influence of parameters such as surfactant
      concentration and molecular length on the final morphology of the system is
      explored to explain the experimental results and to understand the incorporation
      of C60 inside micelles. Both neutral and charged amphiphilic molecules are
      simulated. The long-discussed problem of the location of fullerenes in micelles
      is addressed and C60 is found in the hydrocarbon-chain region of the micelles. If
      the available hydrophobic space increases, C60 is localized in the inner part of
      the micellar core. Short, charged amphiphilic stabilizers are more efficient at
      dispersing fullerenes monomolecularly. Two different phases of C60 are observed
      as the C60/surfactant ratio varies. In the first, aggregates of C60 are entrapped
      inside the micelles, whereas, in the second, colloidal nanoC60 is formed with
      surfactants adsorbed on the surface.

PMID- 25060855
TI  - Meta-analysis of the risk of cataract in type 2 diabetes.
AB  - BACKGROUND: This meta-analysis aimed to investigate the association between type
      2 diabetes (T2D) and the risk of cataract. METHODS: Databases of Pubmed, Embase,
      and SpringerLink were retrieved for observational studies published before
      November 2013. The odds ratio (OR) and 95% confidence interval (CI) were used for
      estimating the association. All statistical analyses were performed by Stata 10.0
      software. RESULTS: A total of 8 studies involving 20837 subjects were included in
      the meta-analysis. The risk of any cataract (AC) in T2D patients was higher than
      that in non-diabetic subjects (OR = 1.97, 95% CI: 1.45-2.67, P < 0.001). The
      risks of cortical cataract posterior (CC) (OR = 1.68, 95% CI: 1.47-1.91, P <
      0.001) and posterior subcapsular (PSC) (OR = 1.55, 95% CI: 1.27-1.90, P < 0.001)
      were significantly elevated in T2D patients, while no significant association was
      found in nuclear sclerosis (NS) (OR = 1.36, 95% CI: 0.97-1.90, P = 0.070).
      CONCLUSION: T2D patients had a higher risk of cataracts, excepting NS. Special
      attention should be paid on the ophthalmic extermination, especially for cataract
      in T2D patients.

PMID- 25060856
TI  - Utilizing everyday items in play to facilitate hand therapy for pediatric
      patients.
AB  - This article describes how hand therapy for pediatric patients can be enhanced
      through the use of play with everyday items. Playful activities integrate
      purposeful hand skills of pinch, grasp and manipulation, while encouraging the
      child to fully participate in therapy and home programs. By referring to Takata's
      developmental hierarchy of play, therapists can design the sessions to include
      novel, fun and age appropriate activities. The author offers eight sample
      activities for specific therapy goals utilizing inexpensive, everyday items. 

PMID- 25060857
TI  - Overexpression of Wild-Type p53-Induced Phosphatase 1 Confers Poor Prognosis of
      Patients with Nasopharyngeal Carcinoma.
AB  - This study aimed to analyze the expression, clinical significance of proto
      oncogene in nasopharyngeal carcinoma and the biological effect in its cell line
      by siRNA targeting wild-type p53-induced phosphatase 1 (Wip1).
      Immunohistochemistry and western blot were respectively used to analyze Wip1
      protein expression in 85 cases of nasopharyngeal cancer and normal tissues to
      study the relationship between Wip1 expression and clinical factors. Wip1 siRNA
      was transiently transfected into papillary nasopharyngeal carcinoma cell by
      liposome-mediated method and was detected by Quantitative real-time RT-PCR (qRT
      PCR) and western blot. MTT assay, cell apoptosis, migration and invasion were
      also conducted as to the influence of the down-regulated expression of Wip1 that
      might be found on CNE2 cells biological effect. The level of Wip1 protein
      expression was found to be significantly higher in nasopharyngeal cancer tissue
      than normal tissues (P <0.05). There were significant differences between Wip1
      expression and T stages, lymph node metastasis, clinical stages, tumor
      differentiation and radiotherapy response (P < 0.05), regardless of age, gender
      (P > 0.05). Meanwhile, Increased expression of Wip1 was significantly with poor
      overall survival time by Kaplan-Meier analysis (P < 0.05). Wip1 expression
      deletion determines independent risk factors for prognosis of patients with
      nasopharyngeal carcinoma in addition to tumor T stage, clinical stage,
      histological grade and lymph node metastasis outside by Cox-2 in the regression
      analysis (P < 0.05). qRT-PCR and Western blot showed that CNE2 cell transfected
      Wip1 siRNA had a lower relative expressive content than normal cell (P < 0.05).
      MTT assay, cell apoptosis, cell cycles demonstrated that CNE2 cell transfected
      Wip1 siRNA had a lower survival fraction, higher cell apoptosis, more percentage
      of the G0/G1 phases, significant decrease in migration and invasion, and higher
      P53 and P16 protein expression compared with CNE2 cell untransfected Wip1 siRNA
      (P < 0.05). Wip1 protein was increased in nasopharyngeal carcinoma, specifically
      in T stages, lymph node metastasis, clinical stages and tumor differentiation.
      Wip1 may involved in the biological processes of nasopharyngeal cancer cell
      proliferation, apoptosis, and migration and invasion by regulation P53 and P16
      protein expression.

PMID- 25060858
TI  - Overexpression of autophagy-related 16-like 1 in patients with oral squamous cell
      carcinoma.
AB  - Dyregulation of autophagy has been reported in various human cancers including
      oral squamous cell carcinoma (OSCC). The objective of this study was to link
      expression of autophagy-related 16-like 1 (ATG16L1), a protein essential for
      autophagosome formation, to clinical outcome in a cohort of 90 OSCC patients.
      Expression level of ATG16L1 was assessed by immunohistochemistry and an
      immunoreactivity score (IRS), ranging from 0 to 9, was assigned to each case. The
      results were correlated with clinicopathological parameters and outcome of
      patients. Twenty-seven patients (30%) exhibited ATG16L1 overexpression as
      indicated by an IRS of 9. Overexpression of ATG16L1 was significantly associated
      with disease stage (p = 0.001), size (p = 0.031) of the tumor, lymph node
      metastasis (p = 0.004), and histological grade (p = 0.038). ATG16L1
      overexpression significantly affected the overall survival (p = 0.020) and time
      to recurrence (p = 0.031) of OSCC patients in Kaplan-Meier analysis. The present
      study suggested that ATG16L1 may be used as a biomarker for selecting OSCC
      patients with a more aggressive phenotype.

PMID- 25060859
TI  - Channelrhodopsin2 current during the action potential: "optical AP clamp" and
      approximation.
AB  - The most widely used optogenetic tool, Channelrhodopsin2 (ChR2), is both light-
      and voltage-sensitive. A light-triggered action potential or light-driven
      perturbations of ongoing electrical activity provide instant voltage feedback,
      shaping ChR2 current. Therefore, depending on the cell type and the light pulse
      duration, the typically reported voltage-clamp-measured ChR2 current traces are
      often not a good surrogate for the ChR2 current during optically-triggered action
      potentials. We discuss two experimental methods to reveal ChR2 current during an
      action potential: an "optical AP clamp" and its approximation employing measured
      current-voltage curve for ChR2. The methods are applicable to voltage- and light
      sensitive ion currents operating in excitable cells, e.g. cardiomyocytes or
      neurons. 

PMID- 25060860
TI  - Mobility of spiromesifen in packed soil columns under laboratory conditions.
AB  - On percolating water equivalent to 1,156 mm of rainfall, spiromesifen formulation
      did not leach out of 25-cm long columns, and 62.7 % of this was recovered in 5-10
      cm soil depth. In columns treated with the analytical grade, 52.40 % of the
      recovered spiromesifen was confined to 0-5-cm soil depth, with 0.04 % in leachate
      fraction, suggesting high adsorption in soil. Results revealed that percolating
      400 mL of water, residues of enol metabolite of spiromesifen was detected up to
      20-25-cm soil layer, with 23.50 % residues of spiromesifen in this layer and 1.73
      % in the leachate fraction indicating that metabolite is more mobile as compared
      to the parent compound. Results suggested a significant reduction in leaching
      losses of enol metabolite in amended soil columns with 5 % nano clay, farmyard
      manure (FYM), and vermicompost. No enol spiromesifen was recovered in the
      leachate in columns amended with nano clay, vermicompost, and FYM; however,
      85.30, 70.5, and 65.40 %, respectively, was recovered from 0-5 cm-soil depth of
      column after percolating water equivalent to 1,156 mm of rainfall. Spiromesifen
      formulation is less mobile in sandy loam soil than analytical grade spiromesifen.
      The metabolite, enol spiromesifen, is relatively more mobile than the parent
      compound and may leach into groundwater. The study suggested that amendments were
      very effective in reducing the downward mobility of enol metabolite in soil
      column. Further, it resulted in greater retention of enol metabolite in the
      amendment application zone. 

PMID- 25060861
TI  - PAHs in PM2.5 in Zhengzhou: concentration, carcinogenic risk analysis, and source
      apportionment.
AB  - Ambient air samples were collected at two different locations between 2011 and
      2012 in Zhengzhou, China in order to assess the concentration level, health
      risks, as well as the sources of polycyclic aromatic hydrocarbons (PAHs) in
      particulate matter (PM2.5). The mean annual levels of PM2.5 observed at industry
      site and residential site were 172 +/- 121 and 160 +/- 72 MUg m(-3),
      respectively, which were about five times the annual value of proposed PM2.5
      standard (35 MUg m(-3)) in China. The PM2.5 in all daily samples (n = 47) exceeds
      the proposed PM2.5 standard in China (75 MUg m(-3)) at both industrial and
      residential sites. Seasonal variations of PM2.5 showed a clear trend of winter >
      autumn > spring > summer at both sites. The total concentrations of 16 PM2.5
      associated PAHs ranged from 61 +/- 51 to 431 +/- 281 and 38 +/- 25 to 254 +/- 189
      ng m(-3), with mean value of 176 +/- 233 and 111 +/- 146 ng m(-3) at industry and
      residential sites, respectively. The major species were fluoranthene, pyrene,
      chrysene, benzo[b]fluoranthene and benzo[k]fluoranthene, and the concentration
      levels of PAHs in PM2.5 were higher in winter than those of other seasons at both
      sites. The annual mean values of toxicity equivalency concentrations of ?16PAHs
      in PM2.5 were 22.8 and 13.5 ng m(-3) in industry and residential area,
      respectively. In this study, the risk level of adult citizens through inhalation
      exposure to PAHs was calculated. The average estimates of lifetime inhalation
      cancer risks were approximately 8.9 * 10(-7) and 6.3 * 10(-7) for industry and
      residential sites, respectively. The main sources of 16 PAHs from both diagnostic
      ratios and principle component analysis identified as vehicular emissions and
      coal combustion. 

PMID- 25060862
TI  - Routing cancer immunology and immunotherapy from the lab to the clinic 4-5 th
      March 2014, Center for Applied Medical Research and University Clinic, Pamplona,
      Spain.
AB  - New approaches to generate effective anticancer responses by either inducing
      immune responses or inhibiting immunosuppression are under development to improve
      efficacy in patients. On March 4-5th, 2014, a symposium was held in Pamplona,
      Spain, to report the new strategies showing preclinical and clinical results
      regarding translational research efforts on the topic. Participants interacted
      through oral presentations of 15 speakers and further discussions on topics that
      included novel therapeutic agents for cancer immunotherapy, viral vectors and
      interferon-based approaches, experimental tumor imaging and immunostimulatory
      monoclonal antibodies. Promising agents to target cancer cells and therapeutic
      approaches that are under translation from bench to patients were presented. 

PMID- 25060863
TI  - Supramolecular activation of a molecular photocatalyst.
AB  - The effects of the planar aromatic organic molecules anthracene and pyrene on the
      catalytic performance of the intramolecular hydrogen evolving photocatalyst
      [Ru(tbbpy)2(tpphz)PdCl2](PF6)2 functioning as a photocatalytic dyad have been
      studied. (1)H-NMR studies on [Ru(tbbpy)2(tpphz)PdCl2](PF6)2 and
      [Ru(tbbpy)2(tpphz)](PF6)2 show a pronounced interaction of pyrene with the
      ruthenium complexes due to pi-pi-interactions. The solid state structure of
      [Ru(tbbpy)2(tpphz)PdCl2]2[Mo8O24] shows a pronounced pi-pi-stacking of the
      polyaromatic ligands. In addition, dimerization constants for the complexes and
      association constants between the complexes and pyrene were determined. Studies
      on the photocatalytic hydrogen production show a decreased induction phase and
      increased turn over frequencies during the initial phase of the catalysis in the
      presence of anthracene and pyrene utilising the catalyst
      [Ru(tbbpy)2(tpphz)PdCl2](PF6)2 irrespective of the nature of the polycyclic
      aromatic hydrocarbon. 

PMID- 25060864
TI  - Direct detection of FoxP3 expression in thymic double-negative CD4-CD8- cells by
      flow cytometry.
AB  - Foxp3 expression is a marker of regulatory T cells (Treg), but how early it is
      expressed in the thymus is still not fully defined. In this study, we examined
      Foxp3 expression in double-negative (DN) CD4(-)CD8(-) T cell precursors in the
      thymus by flow cytometry. By increasing the number of collected cells from the
      conventional 10(4) cells up to more than 10(6) cells during flow cytometry, we
      found that DN cells exhibited higher Foxp3 expression than double-positive (DP)
      CD4(+)CD8(+) and single-positive (SP) CD4(+) or CD8(+) (SP) T cells. CD44(+)
      expression positively correlated with Foxp3 in thymic DN cells. Furthermore, TCR
      beta(-)CD25(+) DN cells exhibited the highest frequency of Foxp3-expressing
      cells. Almost all Foxp3(+) cells expressed CD25in DN cells. These results suggest
      that Foxp3 expression in DN cells can directly be detected by flow cytometry and
      it was positively corelated with CD25 and CD44 in DN cells. 

PMID- 25060865
TI  - [Fat grafting to improve severe tuberous breast].
AB  - INTRODUCTION: Tuberous breast is a rare malformation that has major, negative
      physical and psychological impacts during puberty. A range of surgical techniques
      has been used to correct breast shape and volume in this context. Most techniques
      are based on a combination of skin plasty and mammary gland remodelling, in order
      to redistribute volumes. Prostheses and local-regional flaps can also be used to
      correct the missing volume. Fat grafting to the breast has been used in our
      department since 1998 as a complementary technique in breast reconstruction; it
      constitutes a natural way of providing volume and modifying the shape of the
      breast. Since 2000, we have extended this lipomodelling technique to the
      correction of thorax malformations in general and tuberous breasts in particular.
      Here, we describe our experience of the correction of severe tuberous breasts by
      fat grafting. PATIENTS AND METHODS: Over an 11-year period, we performed a
      retrospective study on tuberous breast patients treated solely with fat grafting
      (i.e. without using an implant). Each breast deformation was graded according to
      the Grolleau classification. After aspiration, the fat was centrifuged and then
      transferred with a specific cannula. Using an 18-G trocar, we sometimes also
      performed fasioctomies to free up fibrous bridges and mammary gland remodelling.
      We evaluated the lipofilling for each case (number of sessions and mean fat
      transfer volume). Technical efficacy was evaluated in terms of patient's
      satisfaction and the surgeon's opinion. Safety was evaluated by screening for
      recipient site complications. RESULTS: We performed a retrospective study of 31
      cases of tuberous breasts treated between January 2000 and December 2010. The
      severe tuberous breasts were type 3 in 10 cases. The mean patient age was 21 and
      the mean body mass index was 21.5. Two session (mean transfer volume: 380 cc)
      were required in every case. The mean follow-up period after the last fat
      transfer session was 6 years (range: 1-11). The patients were very satisfied in
      90% of cases (n=9) and satisfied in 10% of cases (n=1). No complications were
      observed. Imaging performed before surgery and one year afterwards did not reveal
      any anomalies, other than oil cysts. CONCLUSION: The treatment of severe tuberous
      breast with fat grafting is a reliable technique that produces excellent results
      and high levels of patient satisfaction. The aesthetic outcome is natural,
      implant-free and long-lasting. Fat grafting decreases local fibrosis and helps
      (along with fasciotomies and mammary gland remodelling) modify the shape of the
      breast. The technique corrects the missing volume in a precise, personalized
      manner. Lipomodelling efficacy and absence of complications have made it our
      reference treatment for the correction of severe tuberous breasts (as long as the
      patient has sufficient adipose reserves).

PMID- 25060866
TI  - [Epidemiology of maternal mortality by infectious cause in France, 2007-2009,
      using data from confidential maternal mortality report].
AB  - Although deaths caused by infection during pregnancy and the postpartum period
      are rare in France, mortality rates have increased in several countries of the
      European community. In France, the rate of maternal mortality by infectious cause
      has decreased over the last 12 years. Infectious causes are currently in fifth
      place of maternal deaths. Over the period 2007-2009, 18 deaths occurred, eight by
      direct infectious causes and 10 by indirect infectious causes. Among the 18
      deaths, 17 were examined by the National Expert Committee on Maternal Mortality
      (CNEMM) with the objectives to determine the direct or indirect link with
      pregnancy, the adequacy of care and the preventability of death. Among 8 deaths
      from direct infectious causes, four deaths were deemed "preventable" or "possibly
      preventable" because of inadequate care. Among nine deaths from indirect
      infectious causes, preventability could not be established in two deaths, five
      were non-preventable and two were preventable due to non-optimal care. These
      cases of puerperal septicemia show that when sepsis is clinically manifest,
      infection is already well established and widespread deterioration is therefore
      often irreversible. Maternal mortality is preventable in most cases if several
      points are observed: early diagnosis, probabilistic antibiotics targeting most
      frequently involved bacteria including Escherichia coli and Streptococcus A,
      early transfer to ICU, control septic portal entry, simple preventive measures,
      influenza vaccination. A "microbiological clinical diagnosis" approach must be
      initiated at the first clinical signs.

PMID- 25060867
TI  - [Work-related distal radio-ulnar joint injury reported by an obstetrician... a
      rare complication of caesarean section].

PMID- 25060874
TI  - Community pediatric faculty--a valued but endangered resource.

PMID- 25060875
TI  - 50 years ago in the Journal of Pediatrics: an etiologic and diagnostic study of
      cerebral palsy.

PMID- 25060876
TI  - 50 years ago in the Journal of Pediatrics: nitrogen excretion by newborn infants
      during oxygen breathing.

PMID- 25060877
TI  - 50 years ago in the Journal of Pediatrics: the pattern of hearing following acute
      otitis media.

PMID- 25060878
TI  - 50 years ago in the Journal of Pediatrics: needle biopsy of the liver in infants
      and children.

PMID- 25060879
TI  - 50 years ago in the Journal of Pediatrics: a practical, quantitative method for
      recognizing behavioral illness in boys 9 to 14 years of age.

PMID- 25060880
TI  - Diversity and differences of postgraduate training in general and subspecialty
      pediatrics in the European Union.

PMID- 25060881
TI  - The importance of connections between the cell wall integrity pathway and the
      unfolded protein response in filamentous fungi.
AB  - In the external environment, or within a host organism, filamentous fungi
      experience sudden changes in nutrient availability, osmolality, pH, temperature
      and the exposure to toxic compounds. The fungal cell wall represents the first
      line of defense, while also performing essential roles in morphology, development
      and virulence. A polarized secretion system is paramount for cell wall
      biosynthesis, filamentous growth, nutrient acquisition and interactions with the
      environment. The unique ability of filamentous fungi to secrete has resulted in
      their industrial adoption as fungal cell factories. Protein maturation and
      secretion commences in the endoplasmic reticulum (ER). The unfolded protein
      response (UPR) maintains ER functionality during exposure to secretion and cell
      wall stress. UPR, therefore, influences secretion and cell wall homeostasis,
      which in turn impacts upon numerous fungal traits important to pathogenesis and
      biotechnology. Subsequently, this review describes the relevance of the cell wall
      and UPR systems to filamentous fungal pathogens or industrial microbes and then
      highlights interconnections between the two systems. Ultimately, the possible
      biotechnological applications of an enhanced understanding of such regulatory
      systems in combating fungal disease, or the removal of natural bottlenecks in
      protein secretion in an industrial setting, are discussed. 

PMID- 25060882
TI  - Early assessment of chronic kidney dysfunction using contrast-enhanced
      ultrasound: a pilot study.
AB  - OBJECTIVE: We performed a prospective study to evaluate the value of contrast
      enhanced (CE) ultrasound in quantitative evaluation of renal cortex perfusion in
      patients with chronic kidney dysfunction (CKD Stage I-II). METHODS: The present
      study was approved by the institutional ethics committee. The study focused on 41
      consecutive patients (males, 32; females, 9; mean age, 55.0 +/- 5.0 years) with
      clinical suspicion of CKD (Stages I-II). For both kidneys, CE ultrasound was
      performed after intravenous bolus injection of 1.0 ml SonoVue(r) (Bracco Imaging
      S.p.A., Milan, Italy). Time-intensity curves (TICs) and quantitative indexes were
      created with Qlab software (Philips, Bothell, WA). 45 healthy volunteers were
      included as control group. All statistical analyses were performed with SPSS(r)
      v. 15.0 software package (SPSS, Chicago, IL). A difference was considered
      statistically significant with p < 0.05. RESULTS: Patients with CKD (Stages I-II)
      had no obvious change in the shape of TICs. Among all quantitative indexes, the
      changes of area under the curve (AUC), derived peak intensity (DPI) and slope
      rate of elevation curve (A) were statistically significant (p < 0.05). DPI <12
      dB, A >2 and AUC >1300 dB s had high utility in the evaluation of CKD, with 81%,
      73% and 78% specificities and 76%, 73% and 77% sensitivities. CONCLUSION: CE
      ultrasound might be valuable in the early evaluation of CKD. AUC, A and DPI might
      be valuable quantitative indexes. ADVANCES IN KNOWLEDGE: Quantitative CE
      ultrasound analysis can be used for the standardized and early evaluation of
      renal dysfunction.

PMID- 25060883
TI  - Antioxidant activities of rice bran protein hydrolysates in bulk oil and oil-in
      water emulsion.
AB  - BACKGROUND: Recently, utilization of natural antioxidants in food processing has
      been of growing interest, owing to the concerns of health hazards of synthetic
      agents. Protein hydrolysates are a potent candidate for this purpose. In this
      work, rice bran protein hydrolysates (RBPH) with various degrees of hydrolysis
      (DH) were prepared, and their antioxidant activities in soybean oil and oil-in
      water (O/W) emulsion were examined. RESULTS: With increasing DH, RBPH showed
      increasing antioxidant activities, as evidenced by the increases in DPPH radical
      scavenging activity, reducing power and ferrous chelating activity (P < 0.05).
      The improved activity was associated with increasing surface hydrophobicity
      (SoANS). After hydrolysis for 60 min, the content of hydrophobic amino acids was
      increased. When RBPH with various DH were incorporated into bulk soybean oil and
      O/W emulsion stored at 37  degrees C for up to 15 days, lipid oxidation was
      successfully retarded, especially when DH increased. The efficiency in prevention
      of oxidation was dose dependent (0-10 g L(-1)), as indicated by the lower
      peroxide value and thiobarbituric reactive substances. CONCLUSION: The present
      work suggests that RBPH might be potently employed as a natural antioxidant in
      both bulk oil and emulsion models.

PMID- 25060885
TI  - Partial duct ligation: beta-cell proliferation and beyond.

PMID- 25060886
TI  - Diabetes and cardiovascular disease in older adults: current status and future
      directions.
AB  - The prevalence of diabetes increases with age, driven in part by an absolute
      increase in incidence among adults aged 65 years and older. Individuals with
      diabetes are at higher risk for cardiovascular disease, and age strongly predicts
      cardiovascular complications. Inflammation and oxidative stress appear to play
      some role in the mechanisms underlying aging, diabetes, cardiovascular disease,
      and other complications of diabetes. However, the mechanisms underlying the age
      associated increase in risk for diabetes and diabetes-related cardiovascular
      disease remain poorly understood. Moreover, because of the heterogeneity of the
      older population, a lack of understanding of the biology of aging, and inadequate
      study of the effects of treatments on traditional complications and geriatric
      conditions associated with diabetes, no consensus exists on the optimal
      interventions for older diabetic adults. The Association of Specialty Professors,
      along with the National Institute on Aging, the National Institute of Diabetes
      and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute,
      and the American Diabetes Association, held a workshop, summarized in this
      Perspective, to discuss current knowledge regarding diabetes and cardiovascular
      disease in older adults, identify gaps, and propose questions to guide future
      research. 

PMID- 25060888
TI  - Heparanase shakes hands with lipoprotein lipase: a tale of two cells.

PMID- 25060887
TI  - Metformin pharmacogenomics: current status and future directions.
AB  - The incidence of type 2 diabetes (T2D) and its costs to the health care system
      continue to rise. Despite the availability of at least 10 drug classes for the
      treatment of T2D, metformin remains the most widely used first-line
      pharmacotherapy for its treatment; however, marked interindividual variability in
      response and few clinical or biomarker predictors of response reduce its optimal
      use. As clinical care moves toward precision medicine, a variety of broad
      discovery-based "omics" approaches will be required. Technical innovation,
      decreasing sequencing cost, and routine sample storage and processing has made
      pharmacogenomics the most widely applied discovery-based approach to date. This
      opens up the opportunity to understand the genetics underlying the
      interindividual variation in metformin responses in order for clinicians to
      prescribe specific treatments to given individuals for better efficacy and
      safety: metformin for those predicted to respond and alternative therapies for
      those predicted to be nonresponders or who are at increased risk for adverse side
      effects. Furthermore, understanding of the genetic determinants of metformin
      response may lead to the identification of novel targets and development of more
      effective agents for diabetes treatment. The goals of this workshop sponsored by
      the National Institute of Diabetes and Digestive and Kidney Diseases were to
      review the state of research on metformin pharmacogenomics, discuss the
      scientific and clinical hurdles to furthering our knowledge of the variability in
      patient responses to metformin, and consider how to effectively use this
      increased understanding to improve patient outcomes. 

PMID- 25060889
TI  - Of bugs and men: antigen-fortified Lactoccoccus lactis for type 1 diabetes
      immunotherapy.

PMID- 25060890
TI  - Exercise and mitochondrial function in adipose biology: all roads lead to NO.

PMID- 25060891
TI  - Metformin pharmacogenomics: biomarkers to mechanisms.

PMID- 25060892
TI  - Improved mitochondrial function is linked with improved insulin sensitivity
      through reductions in FFA.

PMID- 25060893
TI  - Bilirubin: a potential biomarker and therapeutic target for diabetic nephropathy.

PMID- 25060894
TI  - Is there cross talk between portal and hypothalamic glucose-sensing circuits?

PMID- 25060896
TI  - Comment on Ye et al. The association between circulating lipoprotein(a) and type
      2 diabetes: is it causal? Diabetes 2014;63:332-342.

PMID- 25060897
TI  - Response to comment on Ye et al. The association between circulating
      lipoprotein(a) and type 2 diabetes: is it causal? Diabetes 2014;63:332-342.

PMID- 25060898
TI  - Central aortic cannulation for Stanford type a aortic dissection with the use of
      three-dimensional and two-dimensional transesophageal echocardiography.
AB  - BACKGROUND: There is still significant disagreement among surgeons about the best
      method for arterial cannulation to institute cardiopulmonary bypass (CPB) in
      patients with acute type A aortic dissection (STAADs). This study aimed to
      provide support for central aortic cannulation as a viable and preferable option,
      as it reduces time to institute CPB, operative times, and decreases the
      complexity of the procedure. METHODS: This study is a retrospective review of 34
      patients who underwent STAAD repairs consecutively between October 2006 and
      January 2014. The sample was analyzed for method of cannulation, CPB time, cross
      clamp time, circulatory arrest time, mortality, and complication rate.
      Statistical analysis was performed to compare a control group of patients who
      underwent nonaortic cannulation. RESULTS: The most common method of cannulation
      was the distal aortic arch, which also produced the lowest relative mortality.
      The 30-day mortality was found to be 17.6%. Arrhythmia, acute renal injury, and
      failure to extubate within 48  hours were the most frequent complications, and
      cerebrovascular accidents occurred in three patients (8.8%). Statistically
      significant differences in bypass and cardiac arrest times favored aortic
      cannulation. CONCLUSIONS: This study supports the notion that central aortic
      cannulation is a viable option for CPB in STAAD repair, but further prospective,
      randomized trials are necessary for the procedure to replace peripheral
      cannulation techniques.

PMID- 25060899
TI  - New models to enhance the assessment of mortality risk in low model for end-stage
      liver disease patients: "objectifying" the subjective.

PMID- 25060901
TI  - Synthesis and in vitro antiproliferative activity of thiazole-based nitrogen
      mustards: the hydrogen bonding interaction between model systems and nucleobases.
AB  - Synthesis, characterization and investigation of antiproliferative activity of
      eight thiazole-based nitrogen mustard against human cancer cells lines (MV4-11,
      A549, HCT116 and MCF-7) and normal mouse fibroblast (BALB/3T3) are presented.
      Their structures were determined using NMR, FAB MS, HRMS and elemental analyses.
      Among the derivatives, 3a, 3b, 3e and 3h were found to exhibit high activity
      against human leukemia MV4-11 cells with IC50 values of 0.634-3.61 ug/ml. The
      cytotoxic activity of compound 3a against BALB/3T3 cells is up to 40 times lower
      than against cancer cell lines. Our data indicated also that compound 3e had very
      strong activity against MCF-7 and HCT116 with IC50 equal to 2.32 ug/ml and 2.81
      ug/ml, respectively. Their activity was similar to the activity of cis-platin,
      which is clinically used as anticancer drug in the treatment of human solid
      tumours. We also perform quantum chemical calculation of interaction and binding
      energies in complexes of model systems and 3e with DNA bases. Interaction of real
      drug 3e with guanine is much stronger than with the remaining nucleobases, and
      the strongest among all investigated complexes. Computer simulations were
      performed with ATP-binding domain and DNA-binding site of hTopoII. Compounds 3a-h
      were recognized as potential inhibitors of hTopoII. 

PMID- 25060900
TI  - Real-time evaluation of two light delivery systems for photodynamic disinfection
      of Candida albicans biofilm in curved root canals.
AB  - Antimicrobial photodynamic therapy (APDT) combined with endodontic treatment has
      been recognized as an alternative approach to complement conventional root canal
      disinfection methods on bacterial biofilms. We developed an in  vitro model of
      bioluminescent Candida albicans biofilm inside curved dental root canals and
      investigated the microbial reduction produced when different light delivery
      methods are employed. Each light delivery method was evaluated in respect to the
      light distribution provided inside curved root canals. After conventional
      endodontic preparation, teeth were sterilized before canals were contaminated by
      a bioluminescent strain of C. albicans (CEC789). Methylene blue (90 MUM) was
      introduced into the canals and then irradiated (lambda = 660 nm, P = 100 mW, beam
      diameter = 2 mm) with laser tip either in contact with pulp chamber or within the
      canal using an optical diffuser fiber. Light distribution was evaluated by CCD
      camera, and microbial reduction was monitored through bioluminescence imaging.
      Our findings demonstrated that the bioluminescent C. albicans biofilm model had
      good reproducibility and uniformity. Light distribution in dental tissue was
      markedly dependent on the light delivery system, and this strategy was directly
      related to microbial destruction. Both light delivery systems performed
      significant fungal inactivation. However, when irradiation was performed with
      optical diffuser fiber, microbial burden reduction was nearly 100 times more
      effective. Bioluminescence is an interesting real-time analysis to endodontic C.
      albicans biofilm inactivation. APDT showed to be an effective way to inactivate
      C. albicans biofilms. Diffuser fibers provided optimized light distribution
      inside curved root canals and significantly increased APDT efficiency. 

PMID- 25060902
TI  - Ellagic acid inhibits VEGF/VEGFR2, PI3K/Akt and MAPK signaling cascades in the
      hamster cheek pouch carcinogenesis model.
AB  - BACKGROUND: Blocking vascular endothelial growth factor (VEGF) mediated tumor
      angiogenesis by phytochemicals has emerged as an attractive strategy for cancer
      prevention and therapy. METHODS: We investigated the anti-angiogenic effects of
      ellagic acid in a hamster model of oral oncogenesis by examining the transcript
      and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha), VEGF,
      VEGFR2, and the members of the PI3K/Akt and MAPK signaling cascades. Molecular
      docking studies and cell culture experiments with the endothelial cell line
      ECV304 were performed to delineate the mechanism by which ellagic acid regulates
      VEGF signaling. RESULTS: We found that ellagic acid significantly inhibits HIF
      1alpha-induced VEGF/VEGFR2 signalling in the hamster buccal pouch by abrogating
      PI3K/Akt and MAPK signaling via downregulation of PI3K, PDK-1, p-Akt(ser473),
      mTOR, p-ERK, and p-JNK. Ellagic acid was also found to reduce the expression of
      histone deacetylases that could inhibit neovascularization. Analysis of the
      mechanism revealed that ellagic acid inhibits hypoxia-induced angiogenesis via
      suppression of HDAC-6 in ECV304 cells. Furthermore, knockdown of endogenous HDAC6
      via small interfering RNA abrogated hypoxia-induced expression of HIF-1alpha and
      VEGF and blocked Akt activation. Molecular docking studies confirmed interaction
      of ellagic acid with upstream kinases that regulate angiogenic signaling.
      CONCLUSIONS: Taken together, these findings demonstrate that the anti-angiogenic
      activity of ellagic acid may be mediated by abrogation of hypoxia driven
      PI3K/Akt/mTOR, MAPK and VEGF/VEGFR2 signaling pathways involving suppression of
      HDAC6 and HIF-1alpha responses. GENERAL SIGNIFICANCE: Ellagic acid offers promise
      as a lead compound for anticancer therapeutics by virtue of its ability to
      inhibit key oncogenic signaling cascades and HDACs.

PMID- 25060903
TI  - Steroid treatment can improve the impaired quality of life of patients with
      acquired idiopathic generalized anhidrosis.

PMID- 25060904
TI  - Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia.
AB  - Hypoxia has been previously shown to inhibit the dihydroceramide (DHC)
      desaturase, leading to the accumulation of DHC. In this study, we used metabolic
      labeling with [3H]-palmitate, HPLC/MS/MS analysis, and specific inhibitors to
      show numerous sphingolipid changes after oxygen deprivation in cerebral
      microendothelial cells. The increased DHC, particularly long-chain forms, was
      observed in both whole cells and detergent-resistant membranes. This was reversed
      by reoxygenation and blocked by the de novo sphingolipid synthesis inhibitor
      myriocin, but not by the neutral sphingomyelinase inhibitor GW-4869. Furthermore,
      oxygen deprivation of microendothelial cells increased levels of dihydro
      sphingosine (DH-Sph), DH-sphingosine1-phosphate (DH-S1P), DH-sphingomyelin (DH
      SM), DH-glucosylceramide (DH-GlcCer), and S1P levels. In vitro assays revealed no
      changes in the activity of sphingomyelinases or sphingomyelin synthase, but
      resulted in reduced S1P lyase activity and 40% increase in glucosylceramide
      synthase (GCS) activity, which was reversed by reoxygenation. Inhibition of the
      de novo sphingolipid pathway (myriocin) or GCS (EtPoD4) induced endothelial
      barrier dysfunction and increased caspase 3-mediated cell death in response to
      hypoxia. Our findings suggest that hypoxia induces synthesis of S1P and multiple
      dihydro-sphingolipids, including DHC, DH-SM, DH-GlcCer, DH-Sph and DH-S1P, which
      may be involved in ameliorating the effects of stroke . Progressive hypoxia leads
      to the accumulation of several dihydrosphingolipids in cerebral microendothelial
      cells. Hypoxia also increases sphingosine-1-phosphate and the activity of
      glucosylceramide (Glc-Cer) synthase. These changes reverse by inhibiting the de
      novo sphingolipid synthesis, which worsens hypoxia-induced endothelial barrier
      dysfunction and apoptosis, suggesting that the identified sphingolipids may be
      vasculoprotective. 

PMID- 25060905
TI  - Reply to long-term survivorship clinics led by primary care physicians within the
      cancer center may be a good option for coordinated survivorship care.

PMID- 25060906
TI  - Changes in telomere length distribution in low-dose X-ray-irradiated human
      umbilical vein endothelial cells.
AB  - Ionizing radiation (IR) is known to be a cause of telomere dysfunction in tumor
      cells; however, very few studies have investigated X-ray-related changes in
      telomere length and the telomerase activity in normal human cells, such as
      umbilical vein endothelial cells (HUVECs). The loss of a few hundred base pairs
      from a shortened telomere has been shown to be important with respect to cellular
      senescence, although it may not be detected according to traditional mean
      telomere length [assessed as the terminal restriction fragment (TRF)] analyses.
      In the present study, a continuous time window from irradiation was selected to
      examine changes in the telomere length, including the mean TRF length, percentage
      of the telomere length, telomerase activity, apoptotic rate, and survival rate in
      HUVECs from the first day to the fourth day after the administration of a 0.5-Gy
      dose of irradiation. The mean TRF length in the irradiated HUVECs showed shorter
      telomere length in first 3 days, but they were not statistically significant. On
      the other hand, according to the percentage analysis of the telomere length, a
      decreasing tendency was noted in the longer telomere lengths (9.4-4.4 kb), with a
      significant increase in the shortest telomeres (4.4-2.3 kb) among the irradiated
      cells versus the controls from the first day to the third after irradiation; no
      significant differences were noted on the fourth day. These results suggest that
      the shortest telomeres are sensitive to the late stage of radiation damage. The
      proliferation of irradiated cells was suppressed after IR in contrast to the non
      irradiated cells. The apoptotic rate was elevated initially both in IR- and non
      IR-cells, but that of IR-cells was maintained at an elevated level thereafter in
      contrast to that of non-IR-cells decreasing promptly. Therefore, a 0.5-Gy dose of
      IR induces persistent apoptosis leading to an apparent growth arrest of the
      normal HUVECs.

PMID- 25060907
TI  - Taurine prevents high glucose-induced angiopoietin-2/tie-2 system alterations and
      apoptosis in retinal microvascular pericytes.
AB  - Previously, we confirmed that taurine prevented diabetes-induced apoptosis in
      retinal glial cells via its anti-oxidation and anti-glutamate excitotoxicity
      mechanisms. The aim of this study is to investigate the effects of taurine on
      angiopoietin-2 (Ang-2)/Tie-2 system expressions and apoptosis in high glucose
      treated retinal microvascular pericytes (RMPs). Also, the possible mechanism
      involved in the inhibition of taurine on RMPs apoptosis is investigated. The
      expressions of Ang-2, Tie-2 were detected by qRT-PCR and ELISA. The level of
      phosphorylated Tie-2 (P-Tie-2) was examined by ELISA. Hoechst 33342 and Annexin
      V/PI staining were used to detect RMPs apoptosis. The activity of caspase-3 was
      detected by assay kit. In 25 mM high glucose group, the expression of Ang-2 was
      increased significantly, taurine down-regulated Ang-2 in a dose (0.1, 1, and 10
      mM)-dependent manner (P < 0.05). The Tie-2 expression and P-Tie-2 level were
      decreased in high glucose group (P < 0.05). Interestingly, taurine at 1 and 10 mM
      showed significant increase in Tie-2 expression and P-Tie-2 level (P < 0.05). The
      number of apoptotic RMPs and the activity of caspase-3 increased in the presence
      of high glucose (P < 0.05). Treatment with taurine at 1 mM decreased the number
      of apoptotic RMPs and the activity of caspase-3 (P < 0.05). Blocking antibody and
      small interfering RNA (siRNA) treatment showed that taurine required Tie-2 to
      perform its anti-apoptotic effect. Taken together, our data suggest that high
      glucose-induced Ang-2/Tie-2 system expressions alteration can be reversed by
      taurine, and that taurine can inhibit high glucose-induced RMPs apoptosis via Tie
      2.

PMID- 25060908
TI  - Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and
      cerulein-induced rat model of pancreatitis.
AB  - Inflammasomes are protein complexes formed in response to tissue injury and
      inflammation to regulate the formation of proinflammatory cytokines. Nod-like
      receptor pyrin domain containing 3 (NLRP3) is one such inflammasome involved in
      pancreatic inflammation. Caspase activation recruitment domain (CARD) is an
      interaction motif found in all the major components of NLRP3 inflammasome such as
      apoptosis associated speck-like CARD containing protein (ASC) and procaspase-1.
      NLRP3 activates procaspase-1 with the concerted action of CARD domain of ASC. In
      the present study, the effect of rutin, a natural flavonoid on the expression of
      ASC of NLRP3, was investigated in rats treated with ethanol (EtOH) and cerulein
      (Cer). Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats
      were fed normal diet, whereas groups 3 and 4 rats were fed EtOH (36 % of total
      calories) containing diet for a total period of 5 weeks and also administered Cer
      (20 ug/kg body weight i.p.) thrice weekly for the last 3 weeks. In addition,
      groups 2 and 4 rats received daily 100 mg/kg body weight of rutin from third
      week. Rutin co-administration significantly decreased the level of pancreatic
      marker enzymes, oxidative stress markers, inflammatory markers, mRNA expression
      of caspase-1, cytokines, ASC-NLRP3, and protein expression of caspase-1 and ASC
      in rats received EtOH-Cer. The results of the study revealed that rutin can
      reduce inflammation in pancreas probably by influencing the down regulation of
      ASC-NLRP3 which might result in the reduced activation of caspase-1 and
      controlled cytokine production.

PMID- 25060909
TI  - The caspase-8 shRNA-modified mesenchymal stem cells improve the function of
      infarcted heart.
AB  - The beneficial effects of mesenchymal stem cells (MSCs) in cardiac cell therapy
      are greatly limited due to poor survival after transplantation into ischemic
      hearts. Here, we investigated whether caspase 8 small hairpin RNA (shRNA)
      modification enhance human MSCs (hMSCs) survival and improve infarcted heart
      function. Recombinant adenovirus encoding pre-miRNA-155-designed caspase 8 shRNA
      was prepared to inhibit caspase 8 expression in hMSCs. The effect of caspase 8
      shRNA modification on protecting hMSCs from apoptosis under the conditions of
      serum deprivation and hypoxia was tested by Annexin V/PI staining and caspase 8
      activity assay. The caspase 8 shRNA-modified and superparamagnetic iron oxide
      (SPIO)-labeled hMSCs were injected into the border zone of the infarcted region
      of rat heart. Echocardiography and Masson trichrome staining were performed to
      assess heart function and cardiac fibrosis. Our results showed that adenovirus
      mediated caspase 8 shRNA could efficiently inhibit caspase 8 expression in hMSCs.
      Knock-down of caspase 8 expression lead to inhibition of hMSCs apoptosis,
      reduction of caspase 8 activity and up-regulations of HGF, IGF-1 and Bcl-2.
      Transplantation of caspase 8 shRNA-modified hMSCs could significantly improve
      infracted heart function, attenuate cardiac fibrosis. Consistently, the rate of
      cardiomyocyte apoptosis and caspase 8 activity were significantly decreased, and
      the survival rate of transplanted hMSCs was markedly elevated in the myocardium
      receiving caspase 8 shRNA-modified hMSCs transplantation. Together, our findings
      implicated the therapeutic potential of caspase 8 shRNA-modified hMSCs in
      improving the infarcted heart function. 

PMID- 25060910
TI  - Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS
      mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2)
      cells.
AB  - Calycopterin is a flavonoid compound isolated from Dracocephalum kotschyi that
      has multiple medical uses, as an antispasmodic, analgesic, anti-hyperlipidemic,
      and immunomodulatory agents. However, its biological activity and the mechanism
      of action are poorly investigated. Herein, we investigated the apoptotic effect
      of calycopterin against the human hepatoblastoma cancer cell (HepG2) line. We
      discovered that calycopterin-treated HepG2 cells were killed off by apoptosis in
      a dose-dependent manner within 24 h, and was characterized by the appearance of
      nuclear shrinkage, cleavage of poly (ADP-ribose) polymerase and DNA
      fragmentation. Calycopterin treatment also affected HepG2 cell viability: (a) by
      inhibiting cell cycle progression at the G2/M transition leading to growth arrest
      and apoptosis; (b) by decreasing the expression of mitotic kinase cdc2, mitotic
      phosphatase cdc25c, mitotic cyclin B1, and apoptotic factors pro-caspases-3 and 
      9; and (c) increasing the levels of mitochondrial apoptotic-related proteins,
      intracellular levels of reactive oxygen species, and nitric oxide. We further
      examined the phosphorylation of extracellular signal-related kinase (ERK 1/2), c
      Jun N-terminal kinase, and p-38 mitogen-activated protein kinases (MAPKs) and
      found they all were significantly increased in HepG2 cells treated with
      calycopterin. Interestingly, we discovered that treated cells had significantly
      lower Akt phosphorylation. This mode of action for calycopterin in our study
      provides strong support that inhibition of PI3K/Akt and activation of MAPKs are
      pivotal in G2/M cell cycle arrest and apoptosis of human hepatocarcinoma cells
      mediated by calycopterin. 

PMID- 25060911
TI  - Clinical significance of serum epithelial cell adhesion molecule (EPCAM) levels
      in patients with lung cancer.
AB  - Cellular adhesion molecules might be good markers in some types of malignant
      tumors, thus providing useful information in diagnosis and prognosis. The
      objective of this study was to determine the clinical significance of the serum
      levels of epithelial cell adhesion molecule (EPCAM) in lung cancer patients. One
      hundred and thirty lung cancer patients were enrolled in this study. Serum EPCAM
      levels were determined by the solid-phase sandwich ELISA method. Age- and sex
      matched 34 healthy controls were included in the analysis. The median age was 58
      years, ranging 35-80 years. The majority of the patients had NSCLC (83.8 %) and
      stage IV disease (60.8 %). There was no significant difference in the serum EPCAM
      levels between lung cancer patients and healthy controls (p = 0.16). Moreover,
      known clinical variables including age of patient, gender, histology, stage of
      disease, and response to chemotherapy were not found to be correlated with serum
      EPCAM concentrations (p > 0.05). Similarly, no prognostic role was found for
      outcome (1-year survival rate 62 vs. 65.1 %, p = 0.89). In conclusion, serum
      EPCAM concentrations have no diagnostic, predictive, and prognostic roles in lung
      cancer patients.

PMID- 25060912
TI  - Depletion of thymosin beta4 promotes the proliferation, migration, and activation
      of human hepatic stellate cells.
AB  - BACKGROUND & AIMS: It has recently been reported that thymosin beta-4 (Tbeta4)
      has anti-fibrogenic effects in human hepatic stellate cells (HSCs) in vitro, but
      the mechanisms underlying these effects remain unclear. The aim of this study was
      to investigate the roles of Tbeta4 in the proliferation, migration, and
      activation of HSCs. METHODS: Enzyme-linked immunosorbent assays (ELISA),
      immunohistochemistry, and western blot assays were utilized to determine the
      expression levels of Tbeta4 in serum, liver tissues, and LX-2 cells. Tbeta4 was
      depleted in LX-2 cells using small interfering RNAs (siRNAs). Cell proliferation
      was analyzed using cell counting kit-8 (CCK-8) viability assays, and cell
      migration was investigated using wound-healing and transwell migration assays.
      RESULTS: The expression of Tbeta4 was significantly reduced during the
      progression of liver fibrosis. The depletion of Tbeta4 significantly promoted the
      proliferation and migration of LX-2 cells via the activation of the PI3K/Akt
      signaling pathway. The pro-migratory and pro-proliferative effects of Tbeta4
      depletion in LX-2 cells can be counteracted by treatment with the Akt inhibitor
      MK-2206. In addition, Tbeta4 depletion was also associated with the activation of
      HSCs via the enhanced expression of alpha-smooth muscle actin (alpha-SMA) and
      vimentin. CONCLUSIONS: Our results suggest that Tbeta4 participates in liver
      fibrosis by inhibiting the migration, proliferation, and activation of HSCs and
      that Tbeta4 may be an effective target in the treatment of liver fibrosis.

PMID- 25060913
TI  - A 12-week sports-based exercise programme for inactive Indigenous Australian men
      improved clinical risk factors associated with type 2 diabetes mellitus.
AB  - OBJECTIVES: This study assessed the effect of a 12-week sports-based exercise
      intervention on glucose regulation, anthropometry and inflammatory markers
      associated with the prevalence of type 2 diabetes mellitus (T2DM) in Indigenous
      Australian men. DESIGN: Twenty-six inactive Indigenous Australian men (48.6+/-6.6
      years) were randomized into exercise (n=16) or control (n=10)conditions. METHODS:
      Training included ~2-3 days/week for 12 weeks of sports and gym exercises in a
      group environment, whilst control participants maintained normal activity and
      dietary patterns. Pre- and post-intervention testing included: anthropometry,
      peak aerobic capacity, fasting blood chemistry of inflammatory cytokines,
      adiponectin, leptin, cholesterol, glucose, insulin and C-peptide. An oral glucose
      tolerance test measured glucose, insulin and C-peptide 30, 60, 90 and 120min post
      75g glucose ingestion. RESULTS: The exercise condition decreased insulin area
      under the curve (25+/-22%), increased estimated insulin sensitivity (35+/-62%)
      and decreased insulin resistance (9+/-35%; p<0.05), compared with control
      (p>0.05). The exercise condition decreased in body mass index, waist
      circumference and waist to hip ratio (p<0.05), compared to control (p>0.05).
      Leptin decreased in the exercise group, with no changes for adiponectin (p>0.05)
      or inflammatory markers (p>0.05) in either condition. Aerobic fitness variables
      showed significant increases in peak oxygen consumption for the exercise
      condition compared to no change in control (p>0.05). CONCLUSIONS: Findings
      indicate positive clinical outcomes in metabolic, anthropometric and aerobic
      fitness variables. This study provides evidence for sport and group-based
      activities leading to improved clinical risk factors associated with T2DM
      development in clinically obese Indigenous Australian men.

PMID- 25060914
TI  - B-mode and acoustic radiation force impulse (ARFI) imaging of prostate zonal
      anatomy: comparison with 3T T2-weighted MR imaging.
AB  - Prostate cancer (PCa) is the most common non-cutaneous malignancy among men in
      the United States and the second leading cause of cancer-related death. Multi
      parametric magnetic resonance imaging (mpMRI) has gained recent popularity to
      characterize PCa. Acoustic Radiation Force Impulse (ARFI) imaging has the
      potential to aid PCa diagnosis and management by using tissue stiffness to
      evaluate prostate zonal anatomy and lesions. MR and B-mode/ARFI in vivo imaging
      datasets were compared with one another and with gross pathology measurements
      made immediately after radical prostatectomy. Images were manually segmented in
      3D Slicer to delineate the central gland (CG) and prostate capsule, and 3D models
      were rendered to evaluate zonal anatomy dimensions and volumes. Both imaging
      modalities showed good correlation between estimated organ volume and gross
      pathologic weights. Ultrasound and MR total prostate volumes were well correlated
      (R(2) = 0.77), but B-mode images yielded prostate volumes that were larger
      (16.82% +/- 22.45%) than MR images, due to overestimation of the lateral
      dimension (18.4% +/- 13.9%), with less significant differences in the other
      dimensions (7.4% +/- 17.6%, anterior-to-posterior, and -10.8% +/- 13.9%, apex-to
      base). ARFI and MR CG volumes were also well correlated (R(2) = 0.85). CG volume
      differences were attributed to ARFI underestimation of the apex-to-base axis (
      28.8% +/- 9.4%) and ARFI overestimation of the lateral dimension (21.5% +/-
      14.3%). B-mode/ARFI imaging yielded prostate volumes and dimensions that were
      well correlated with MR T2-weighted image (T2WI) estimates, with biases in the
      lateral dimension due to poor contrast caused by extraprostatic fat. B-mode
      combined with ARFI imaging is a promising low-cost, portable, real-time modality
      that can complement mpMRI for PCa diagnosis, treatment planning, and management.

PMID- 25060915
TI  - A cohort study of toner-handling workers on inflammatory, allergic, and oxidative
      stress markers: cross-sectional and longitudinal analyses from 2003 to 2008.
AB  - OBJECTIVES: This study examines the relationship between toner exposure and its
      health effects in terms of biomarkers which are known to assess the damages to
      humans caused by toxic material exposure. METHODS: The subjects were 1504 male
      workers aged below 50 in 2003 in a Japanese toner and photocopier manufacturing
      company. Personal exposure measurements, pulmonary function tests, chest X-ray
      examinations, biomarker measurement, and a questionnaire about respiratory
      symptoms were conducted. We will report about biomarker measurement in this
      study. Cross-sectional survey studies and a longitudinal study from 2003 to 2008
      were conducted. RESULTS: Few significant findings were associated with the toner
      exposure in both the cross-sectional and the longitudinal studies. The higher
      toner exposure concentrations did not induce effects on increasing biomarkers.
      CONCLUSION: There was no evidence of excessive inflammatory, allergic, or
      oxidative stress reaction in toner-handling workers as compared to non-handling
      workers, despite some sporadically significant findings. There are no other
      reports of a longitudinal epidemiological study with regard to toner exposure;
      this report significantly contributes to toner exposure literature. Although in
      the current well-controlled working environment, the toner exposure
      concentrations are quite low; further studies are needed to completely understand
      the health effects toner may have, however small they may be.

PMID- 25060917
TI  - Flexibility in embodied language processing: context effects in lexical access.
AB  - According to embodied theories of language (ETLs), word meaning relies on
      sensorimotor brain areas, generally dedicated to acting and perceiving in the
      real world. More specifically, words denoting actions are postulated to make use
      of neural motor areas, while words denoting visual properties draw on the
      resources of visual brain areas. Therefore, there is a direct correspondence
      between word meaning and the experience a listener has had with a word's referent
      on the brain level. Behavioral and neuroimaging studies have provided evidence in
      favor of ETLs; however, recent studies have also shown that sensorimotor
      information is recruited in a flexible manner during language comprehension
      (e.g., Raposo et al.; Van Dam et al.,), leaving open the question as to what
      level of language processing sensorimotor activations contribute. In this study,
      we investigated the time course of modality-specific contributions (i.e., the
      contribution of action information) as to word processing by manipulating both
      (a) the linguistic and (b) the action context in which target words were
      presented. Our results demonstrate that processes reflecting sensorimotor
      information play a role early in word processing (i.e., within 200 ms of word
      presentation), but that they are sensitive to the linguistic context in which a
      word is presented. In other words, when sensorimotor information is activated, it
      is activated quickly; however, specific words do not reliably activate a
      consistent sensorimotor pattern.

PMID- 25060918
TI  - The influence of bodily experience on children's language processing.
AB  - The Body-Object Interaction (BOI) variable measures how easily a human body can
      physically interact with a word's referent (Siakaluk, Pexman, Aguilera, Owen, &
      Sears, ). A facilitory BOI effect has been observed with adults in language
      tasks, with faster and more accurate responses for high BOI words (e.g., mask)
      than for low BOI words (e.g., ship; Wellsby, Siakaluk, Owen, & Pexman, ). We
      examined the development of this effect in children. Fifty children (aged 6-9
      years) and a group of 21 adults completed a word naming task with high and low
      BOI words. Younger children (aged 6-7 years) did not show a BOI effect, but older
      children (aged 8-9 years) showed a significant facilitory BOI effect, as did
      adults. Magnitude of children's BOI effect was related to age as well as reading
      skills. These results suggest that bodily experience (as measured by the BOI
      variable) begins to influence visual word recognition behavior by about 8 years
      of age.

PMID- 25060919
TI  - Congenital intraosseous cavernous hemangioma of the skull: an unusual case.
AB  - Intraosseous hemangiomas are benign vascular malformations mostly seen in the
      spine. They rarely occur in the skull. The usual age-group involved is the 2nd to
      4th decades, and females outnumber males. We hereby report a rare case of
      congenital intraosseous cavernous hemangioma of the skull bone in a male infant.
      The patient underwent total excision of the lesion.

PMID- 25060920
TI  - Simple fabrication of an organic laser by microcontact molding of a distributed
      feedback grating.
AB  - Lasing from an organic polymer is demonstrated in a device utilizing a
      distributed feedback (DFB) grating, manufactured by microcontact molding of CdSe
      nanocrystals (NCs) directly on top of the emitter layer. Besides the simpler
      fabrication in comparison with a reference device based on a
      photolithographically prepared DFB grating in a bottom dielectric layer, a much
      higher DFB strength for NC-gratings is observed, resulting in reduced lasing
      threshold and a fourfold differential lasing efficiency. 

PMID- 25060921
TI  - Orthogeriatric care pathway: a prospective survey of impact on length of stay,
      mortality and institutionalisation.
AB  - INTRODUCTION: Care pathways for elderly hip fracture patients are increasingly
      implemented but there has been only limited evaluation of their use. Our
      objective was to investigate the impact of such a care pathway on the use of
      healthcare resources and on patients' outcomes. MATERIALS AND METHODS: The
      prospective survey covered 493 hip fracture patients 65 years of age or older
      that were treated either before "Usual Care = (UC)" or after "Co-Managed-Care =
      (CMC)" implementation of the care pathway. Primary outcome was length of stay
      (LoS). Secondary outcomes were 1-year mortality and change in residential status
      from prefracture baseline to 1-year after surgery. Data were analysed by
      descriptive and interferential statistics and adjustment for baseline differences
      amongst the two patient groups was done. RESULTS: Patients in the CMC sample had
      more preexisting comorbidities (CCI 2.5 versus 2.1). Prior to the fracture, a
      larger proportion amongst them needed help in ADL (49 versus 26%), and they were
      more likely to reside in a nursing home (36 versus 29%). Prefracture mobility
      status was equal in both samples. In the CMC sample LoS was significantly shorter
      (LoS 8.6 versus 11.3 days, p < 0.01) and patients were less likely to experience
      a complication (59 vs 73%, p < 0.01) while being in the hospital. There was no
      significant difference in 1-year mortality or in change of residential status.
      CONCLUSIONS: A care pathway for elderly hip fracture patients allowed decreased
      LoS without affecting mortality or change of residential status 1 year after
      fracture compared to prefracture baseline.

PMID- 25060922
TI  - A Medicago truncatula rdr6 allele impairs transgene silencing and endogenous
      phased siRNA production but not development.
AB  - RNA-dependent RNA polymerase 6 (RDR6) and suppressor of gene silencing 3 (SGS3)
      act together in post-transcriptional transgene silencing mediated by small
      interfering RNAs (siRNAs) and in biogenesis of various endogenous siRNAs
      including the tasiARFs, known regulators of auxin responses and plant
      development. Legumes, the third major crop family worldwide, has been widely
      improved through transgenic approaches. Here, we isolated rdr6 and sgs3 mutants
      in the model legume Medicago truncatula. Two sgs3 and one rdr6 alleles led to
      strong developmental defects and impaired biogenesis of tasiARFs. In contrast,
      the rdr6.1 homozygous plants produced sufficient amounts of tasiARFs to ensure
      proper development. High throughput sequencing of small RNAs from this specific
      mutant identified 354 potential MtRDR6 substrates, for which siRNA production was
      significantly reduced in the mutant. Among them, we found a large variety of
      novel phased loci corresponding to protein-encoding genes or transposable
      elements. Interestingly, measurement of GFP expression revealed that post
      transcriptional transgene silencing was reduced in rdr6.1 roots. Hence, this
      novel mis-sense mutation, affecting a highly conserved amino acid residue in
      plant RDR6s, may be an interesting tool both to analyse endogenous pha-siRNA
      functions and to improve transgene expression, at least in legume species. 

PMID- 25060923
TI  - Recent progress in sodium channel modulators for pain.
AB  - Voltage-gated sodium channels (Navs) are an important family of transmembrane ion
      channel proteins and Nav drug discovery is an exciting field. Pharmaceutical
      investment in Navs for pain therapeutics has expanded exponentially due to
      genetic data such as SCN10A mutations and an improved ability to establish an
      effective screen sequence for example IonWorks Barracuda(r), Synchropatch(r) and
      Qube(r). Moreover, emerging clinical data (AZD-3161, XEN402, CNV1014802, PF
      05089771, PF-04531083) combined with recent breakthroughs in Nav structural
      biology pave the way for a future of fruitful prospective Nav drug discovery.

PMID- 25060924
TI  - Improved mapping of interictal epileptiform discharges with EEG-fMRI and voxel
      wise functional connectivity analysis.
AB  - OBJECTIVE: We describe a novel method to spatially map interictal epileptiform
      discharges (IEDs) through voxel-wise functional connectivity analysis of the
      functional magnetic resonance imaging (fMRI) portion of simultaneous
      electroencephalography (EEG)-fMRI data. This method measures the local
      synchronicity of fMRI signals associated with IED and, in contrast to
      conventional methods, does not require modeling of neural activities or
      hemodynamic response. METHODS: Simultaneous EEG-fMRI was performed on six
      patients with focal epilepsy. IED events were detected from the EEG data. The
      fMRI data was subdivided into time segments of 20 s in length, and then
      reorganized into one set of concatenated time series containing the IED events
      and many sets without IEDs. Local degree centrality (LDC), a metric of functional
      connectivity, was computed for each brain voxel to summarize its signal
      correlations to brain voxels within 14 mm of physical distance. This computation
      was repeated for each set of concatenated time series, yielding one whole-brain
      LDC map for time with the IED events and many maps for time without IED. A
      statistical score was computed for each voxel to detect the voxels with
      significant LDC value differences associated with IEDs. The fMRI data were also
      processed separately by conventional methods for comparison. RESULTS: In all six
      patients, regions with significant LDC increase during IEDs were concordant in
      location to both simultaneous EEG and the epileptogenic focus determined from
      separate clinical studies. In contrast, results from the conventional methods
      were concordant in only three patients. SIGNIFICANCE: We show that for focal
      epilepsy, voxel-wise functional connectivity analysis of EEG-fMRI data may
      improve IED localization and EEG concordance compared to the conventional
      analysis. This new analytic method may improve the robustness of interictal EEG
      fMRI as a technique for mapping the epileptogenic focus, and helps study the
      local synchronization aspect of the epileptic network.

PMID- 25060925
TI  - Low-dose radiation-induced apoptosis in human leukemia K562 cells through
      mitochondrial pathways.
AB  - High-dose total body irradiation (TBI) has an established role as preparative
      regimen for bone-marrow transplantation in the treatment of chronic myelogenous
      leukemia (CML), but this regimen still has a relatively high rate of acute and
      late toxicity. Low-dose radiation (LDR) induces apoptosis of tumor cells and has
      numerous beneficial effects on normal tissues, including radiation homeostasis
      and adaptive response. Based on the previous evidence, in the present study, K562
      cells were exposed to LDR, high-dose radiation (HDR), and LDR in combination with
      HDR to investigate the possible mechanism of the apoptotic effect and
      hypersensitivity induced by LDR. The apoptotic rate increased in all radiation
      groups in a time-dependent manner. An upregulation of Bax protein expression and
      a downregulation of Bcl-xl in a dose-dependent manner in human leukemia K562
      cells was observed. However, the expression of p53 protein did not change in all
      of the radiation cell groups. The mitochondrial membrane potential (DeltaPsim) in
      K562 cells decreased in all of the radiation cell groups in a dose-dependent
      manner. Furthermore, the decrease of DeltaPsim was enhanced in the LDR/HDR group
      compared with that in the LDR or HDR groups. The activity of caspase-3 was
      enhanced in all of the radiation groups. In the LDR/HDR group, the activity of
      caspase-3 was higher than that in the HDR or LDR groups. The present study
      provided preliminary experimental evidence of LDR being beneficial in combination
      with TBI in the treatment of CML.

PMID- 25060926
TI  - Sensing propensity of a defected graphane sheet towards CO, H2O and NO2.
AB  - We have used density functional theory to investigate the sensing property of a
      hydrogenated graphene sheet (graphane) towards CO, H2O and NO2 gas molecules.
      Though the pristine graphane sheet is found not to have sufficient affinity
      towards the mentioned gas molecules, the defected sheet (removing few surface H
      atoms) has a strong affinity towards the gas molecules. While CO and H2O are
      found to be weakly physisorbed, the NO2 molecules are found to be strongly chemi
      sorbed to the defected graphane sheet. With NO2, the N(p) and O(p) states are
      found to have strong hybridization with the most active C(p) states which lie at
      the defected site of the graphane sheet. While increasing the coverage effect of
      the mentioned gas molecules toward the defected sheet, the adsorption energies do
      not change significantly. At the same time, the work function of the defected
      graphane sheet shows an increasing trend while adsorbed with CO, H2O and NO2 gas
      molecules, opening up the possibilities for a future gas sensor. 

PMID- 25060928
TI  - Preoperative assessment tool for the planning of inframammary incision and
      implant profile in breast augmentation.
AB  - When using the inframammary access incision for breast augmentation, careful
      planning is critical to allow the surgeon to set the inframammary fold (IMF) at
      the most optimal position, minimize scar visibility, and mitigate the main
      disadvantage of this approach. Current popular evaluation systems for breast
      augmentation include the High Five and Randquist systems and they base their
      calculations on inconsistent variables like skin stretch measurements. We propose
      a simple method that is not dependent on skin stretch measurements to properly
      determine implant size, profile, and position of the inframammary fold. Excluding
      digital scans and computer-based systems that are not universally available, the
      proposed simplified assessment tool was compared to the two most popular manual
      measuring tools (High Five and Randquist). Twenty-five female volunteers were
      included in the study. The projected IMF positions over the midsternal line for
      each measuring tool were recorded on each patient and the sternal notch (SN) to
      projected IMF distance SN-IMF1 (simplified evaluation system), SN-IMF2 (High Five
      System), and SN-IMF3 (Randquist system) were compared. The anticipated new IMF
      position is determined based on the vertical implant dimension and not on breast
      base width. For most subjects, the differences between the three evaluation
      systems were minimal. The proposed breast measurement tool constitutes a new,
      much simpler, and practical method that proved to be successful in our hands.

PMID- 25060927
TI  - Incidence of cervical lymph node metastasis and its association with outcomes in
      patients with adenoid cystic carcinoma. An international collaborative study.
AB  - BACKGROUND: The patterns of regional metastasis in adenoid cystic carcinoma (ACC)
      of the head and neck and its association with outcome is not established.
      METHODS: We conducted a retrospective multicentered multivariate analysis of 270
      patients who underwent neck dissection. RESULTS: The incidence rate of neck
      metastases was 29%. The rate observed in the oral cavity is 37%, and in the major
      salivary glands is 19% (p = .001). The rate of occult nodal metastases was 17%.
      Overall 5-year survival rates were 44% in patients undergoing therapeutic neck
      dissections, and 65% and 73% among those undergoing elective neck dissections,
      with and without nodal metastases, respectively (p = .017). Multivariate analysis
      revealed that the primary site, nodal classification, and margin status were
      independent predictors of survival. CONCLUSION: Our findings support the
      consideration of elective neck treatment in patients with ACC of the oral cavity.

PMID- 25060929
TI  - Performance of multidetector CT in the evaluation of the endometrium: Measurement
      of endometrial thickness and detection of disease.
AB  - AIM: To evaluate the performance of multidetector computed tomography (MDCT) in
      the measurement of endometrial thickness and assessment for endometrial disease.
      MATERIALS AND METHODS: Seventy-nine MDCT examinations, including sagittal
      reformats from isotropic data, were retrospectively evaluated for the presence of
      endometrial abnormality, endometrial thickness, and recommendation for
      transvaginal ultrasound (TVUS) after CT. The endometrial thickness was measured
      on sagittal images using two different methods, between the inner-to-inner
      hypoattenuating stripe, and when visible, between the outer-to-outer
      hyperattenuating stripe. TVUS performed within 48 h of CT in premenopausal and 1
      month in postmenopausal patients served as reference standard. Interobserver
      agreement for endometrial thickness and abnormalities was assessed using
      concordance correlation (CC) and kappa statistics. RESULTS: Interobserver
      agreement for endometrial thickness on sagittal CT images was excellent (CC
      0.98), and highly accurate using the inner-to-inner measurement. For
      determination of abnormal thickening, the positive predictive value and negative
      predictive value were 67-100% and 99.5-100%. For detection of any endometrial
      abnormality, the positive predictive value and negative predictive value were 79
      90% and 84-95%, respectively. False-negative missed abnormalities included small
      volume hydrometra, a polyp, and endometrial distortion by a fibroid. CONCLUSION:
      At MDCT, sagittal reformatted images provide reliable endometrial measurement
      using the inner-to-inner hypoattenuating stripe and are accurately categorized as
      normal or abnormal thickness using the same numerical criteria as at sonography.

PMID- 25060930
TI  - Re: Ultrasonographic elastography of thyroid nodules: Is adding strain ratio to
      colour mapping better? A reply.

PMID- 25060931
TI  - Real-time phase-contrast flow MRI of haemodynamic changes in the ascending aorta
      and superior vena cava during Mueller manoeuvre.
AB  - AIM: To evaluate the potential of real-time phase-contrast flow magnetic
      resonance imaging (MRI) at 40 ms resolution for the simultaneous determination of
      blood flow in the ascending aorta (AA) and superior vena cava (SVC) in response
      to reduced intrathoracic pressure (Mueller manoeuvre). MATERIALS AND METHODS:
      Through-plane flow was assessed in 20 healthy young subjects using real-time
      phase-contrast MRI based on highly undersampled radial fast low-angle shot
      (FLASH) with image reconstruction by regularized non-linear inversion.
      Haemodynamic alterations (three repetitions per subject = 60 events) were
      evaluated during normal breathing (10 s), inhalation with nearly closed
      epiglottis (10 s), and recovery (20 s). RESULTS: Relative to normal breathing and
      despite interindividual differences, reduced intrathoracic pressure by at least
      30 mmHg significantly decreased the initial peak mean velocity (averaged across
      the lumen) in the AA by -24 +/- 9% and increased the velocity in the SVC by +28
      +/- 25% (p < 0.0001, n = 23 successful events). Respective changes in flow volume
      per heartbeat were -25 +/- 9% in the AA and +49 +/- 44% in the SVC (p < 0.0001, n
      = 23). Flow parameters returned to baseline during sustained pressure reduction,
      while the heart rate was elevated by 10% (p < 0.0001) after the start (n = 24)
      and end (n = 17) of the manoeuvre. CONCLUSIONS: Real-time flow MRI during low
      intrathoracic pressure non-invasively revealed quantitative haemodynamic
      adjustments in both the AA and SVC.

PMID- 25060932
TI  - Visualizing cerebral veins in fetal brain using susceptibility-weighted MRI.
AB  - AIM: To explore the feasibility of two-dimensional (2D) susceptibility-weighted
      imaging (SWI) in the visualization of cerebral veins in the foetal brain.
      MATERIALS AND METHODS: Forty-two pregnant healthy women (gestational age: 19-37
      weeks, mean: 28.5 +/- 7.1 weeks) underwent SWI examination using a 1.5 T MRI
      system. Two neurologists independently analysed all magnetic resonance imaging
      (MRI) studies. The relationship between the veins detected and the gestational
      age was investigated. The prominence of veins was assessed using a categorical
      score. RESULTS: In total, 167 veins were detected by SWI in 29 subjects with a
      symmetric hemisphere distribution (p > 0.05). An additional vein was detected by
      SWI biweekly from 24 weeks of gestation. Most veins of Galen and internal
      cerebral veins on SWI images were prominent, whereas others were faint or
      moderate. CONCLUSION: SWI appears to be a feasible method of detecting cerebral
      veins in the foetal brain.

PMID- 25060933
TI  - Low b-value (black blood) respiratory-triggered fat-suppressed single-shot spin
      echo echo-planar imaging (EPI) of the liver: comparison of image quality at 1.5
      and 3 T.
AB  - AIM: To compare echo-planar imaging (EPI) of the liver at 1.5 and 3 T. MATERIALS
      AND METHODS: Under a waiver from the institutional review board, 46 patients
      underwent respiratory-triggered fat-suppressed b = 50 s/mm(2) EPI at 1.5 or 3 T
      between 2010-2013. Thirty liver lesions were included with no therapy performed
      between studies. Signal- and contrast-to-noise ratios (SNR/CNR) were compared
      using a paired t-test. Two blinded readers independently assessed EPI at 1.5 and
      3 T in two separate reading sessions for image quality by hepatic region and the
      presence and severity of artefacts. Results were compared using the Wilcoxon sign
      rank test. Interobserver agreement was assessed using Cohen's kappa statistic.
      RESULTS: There was no difference in mean SNR/CNR at 3 T (20.26 +/- 10.25/9.55 +/-
      15.78); compared to 1.5 T (21.96 +/- 9.75/5.35 +/- 7.89); p = 0.43 and p = 0.09,
      respectively. Image quality was better at 1.5 T for all hepatic regions (p <
      0.001). Image quality was poor or suboptimal at 3 T in 57% of regions studied,
      compared to 5.6% at 1.5 T. With the exception of image blur (p = 0.27), all
      artefacts were more prevalent at 3 T with higher rates of image distortion (p <
      0.001), failed fat suppression (p = 0.002), ghosting (p < 0.001), parallel
      imaging artefact (p < 0.001), and shading (p < 0.001). Interobserver agreement
      was moderate (kappa = 0.43-0.53). CONCLUSION: Fat-suppressed low b-value EPI of
      the liver is significantly better at 1.5 T compared to 3 T.

PMID- 25060934
TI  - Pain following double-bundle anterior cruciate ligament reconstruction:
      correlation with morphological graft findings and dynamic contrast-enhanced MRI.
AB  - AIM: To determine the relationship between knee pain following anterior cruciate
      ligament (ACL) graft placement with morphological graft findings and dynamic
      contrast enhancement as assessed at MRI. MATERIAL AND METHODS: Following
      institutional review board approval, 37 consecutive patients with double-bundle
      ACL reconstruction were enrolled. Thirteen patients had pain and 24 were
      asymptomatic. Imaging was performed using a 1.5 T MRI machine an average of 7.6
      months after surgery. Graft-related (increase signal intensity, abnormal
      orientation, discontinuity, cystic degeneration, anterior translation of lateral
      tibia, arthrofibrosis), and non-graft related causes of knee pain (meniscal tear,
      cartilage injury, loose bodies, and synovitis) were evaluated. During dynamic
      contrast enhancement analysis, peak enhancement (ePeak) was calculated by placing
      a region of interest at the osteoligamentous interface of each bundle. Student's
      t-test was used for continuous variables analysis and chi-square or Fisher's
      exact test was used for categorical variables analysis. RESULTS: There was no
      difference between symptomatic and asymptomatic patients regarding morphological
      graft-related or non-graft-related causes of knee pain. For dynamic contrast
      enhancement analysis, symptomatic patients had significantly lower ePeak values
      than asymptomatic patients in the anteromedial (p = 0.008) and posterolateral (p
      = 0.001) bundles or when using the higher ePeak value in either bundle (p =
      0.003). CONCLUSION: Morphological ACL graft findings as assessed at MRI could not
      be used to distinguish between symptomatic and asymptomatic patients. However,
      lower ePeak values had a significant association with knee pain. This may
      indicate poor neovascularization of the graft, potentially leading to graft
      failure.

PMID- 25060935
TI  - Normal anatomical variants of the menisci and cruciate ligaments that may mimic
      disease.
AB  - There are many normal anatomical variants of the knee joint. Some are common and
      others are rare. With continuing improvements in the spatial resolution of MRI,
      smaller variants are more clearly demonstrated and can be mistaken for disease.
      They can all be differentiated from pathological conditions by understanding
      their anatomy and key differentiating features. This review compares normal
      variants of the menisci and cruciate ligaments with the pathological disorders
      that can mimic them. 

PMID- 25060936
TI  - Radiofrequency ablation guided by contrast-enhanced ultrasound for hepatic
      malignancies: preliminary results.
AB  - AIM: To evaluate whether contrast-enhanced ultrasound (CEUS)-guided
      radiofrequency ablation (RFA) can be performed effectively in small hepatic
      malignancies that are invisible or poorly visualized at traditional grey-scale
      ultrasonography (US). MATERIALS AND METHODS: The institutional ethics committee
      approved the study, and all patients provided written informed consent before
      their enrolment. The study focused on 55 patients (43 men, 12 women, age 57.4 +/-
      10.9 years) with 60 hepatic lesions from May 2010 to March 2011. All lesions were
      treated with multipolar radiofrequency ablation (RFA). During the RFA procedure,
      with the injection of ultrasound contrast agent (sulphur hexafluoride; SonoVue,
      Bracco Imaging Spa, Milan, Italy), RFA was conducted under CEUS guidance when the
      optimal depiction of a lesion was obtained. Artificial pleural effusions were
      used in those cases obstructed by the lungs. Twenty-four hours after RFA,
      contrast-enhanced MRI was used as the reference standard to evaluate the primary
      effectiveness rate and complete tumour necrosis. The follow-up time was 12-24
      months (median 15 months). RESULTS: Among 60 hepatic malignancies, CEUS detected
      57 lesions (95%), which was higher than that at US (26.6%). Artificial pleural
      effusions were performed in three cases, resulting in the detection of three
      additional lesions. The insertion of RFA electrodes was monitored by CEUS in all
      lesions. Immediately after RFA, complete tumour necrosis were achieved in all 60
      lesions as apparent at MRI, for a primary effectiveness rate of 100%. CONCLUSION:
      CEUS-guided RFA is a promising technique for targeting and improving the
      efficiency of treatment of hepatic malignancies.

PMID- 25060937
TI  - Otolaryngological presentations of Cornelia de Lange syndrome.
AB  - AIM: Children with Cornelia de Lange syndrome frequently present to
      otolaryngology services with hearing problems. Airway problems have not
      previously been reported. We wish to describe our experience of the overall
      management in a series of children with Cornelia de Lange syndrome. METHODS:
      Retrospective case note review of children diagnosed with Cornelia de Lange
      syndrome presenting to our department between 2005 and 2014. RESULTS: Six
      patients were seen. Airway problems consisted of laryngeal overspill with severe
      gastroesophageal dysmotility and reflux despite structurally normal airway (1
      case), laryngomalacia requiring supraglottoplasty (2 cases), reflux laryngitis
      with secondary laryngomalacia and coincidental tracheal diverticulum (1 case)
      choanal atresia requiring stents (1 case) and obstructive sleep apnoea (1 case).
      Supraglottoplasty produced a dramatic improvement in feeding and breathing in
      both children who underwent the procedure. Two children had palatal anomalies and
      one underwent cochlear implantation for a profound sensorineural hearing loss.
      CONCLUSION: Children with Cornelia de Lange syndrome have multifaceted ENT
      problems. Airway pathology has not previously been described in Cornelia de Lange
      syndrome but has been common in our experience. We wish to highlight that
      laryngomalacia in Cornelia de Lange syndrome responds well to supraglottoplasty.

PMID- 25060938
TI  - Strategies to prevent biofilm-based tympanostomy tube infections.
AB  - OBJECTIVE: To review the potential contributory role of biofilms to post
      tympanstomy tube otorrhea and plugging as well as the available interventions
      currently utilized to prevent biofilm formation on tympanostomy tubes. DATA
      SOURCES: A literature review was performed utilizing the MEDLINE/Pubmed database
      from 1980 to 2013. REVIEW METHODS: Electronic database was searched with
      combinations of keywords "biofilm", "tympanostomy tube", "ventilation tube", and
      "post-tympanostomy tube otorrhea". RESULTS: Two of the most common sequelae that
      occur after tympanostomy tube insertion are otorrhea and tube occlusion. There is
      an increased evidence supporting a role for biofilms in the pathogenesis of
      otitis media. In this review, we have shown a multitude of novel approaches for
      prevention of biofilm associated sequelae of otitis media with effusion. These
      interventions include (i) changing the inherent composition of the tube itself,
      (ii) coating the tubes with antibiotics, polymers, plant extracts, or other
      biofilm-resistant materials, (iii) tubal impregnation with antimicrobial
      compounds, and (iv) surface alterations of the tube by ion-bombardment or surface
      ionization. CONCLUSION: Currently, there is not one type of tympanostomy tube in
      which bacteria will not adhere. The challenges of treating chronic post
      tympanostomy tube otorrhea and tube occlusion indicate the need for further
      research in optimization of tympanostomy tube design in addition to development
      of novel therapies.

PMID- 25060939
TI  - Direct Streptococcus pneumoniae real-time PCR serotyping from pediatric
      parapneumonic effusions.
AB  - BACKGROUND: To determine the serotypes of Streptococcus pneumoniae responsible
      for pneumonia complicated by parapneumonic effusion in children, we performed
      real-time PCR based pneumococcal "serotyping" directly on parapneumonic fluid
      samples. METHODS: Specimens were collected at two children's hospitals in
      Ontario, Canada from 2009 to 2011. Samples in which S. pneumoniae was detected by
      PCR were tested with serotype-specific 5'exonuclease PCR assays for the 13
      serotypes contained in the 13-serotype pneumococcal vaccine. RESULTS: Thirty-five
      S. pneumoniae PCR-positive pleural samples were studied. Pneumococcal serotyping
      PCR assays were positive for 34 of 35 (97%). Serotype 3 was detected most
      frequently, in 19/35 (54%), followed by serotype 19A in 9/35 (26%), serotype 7
      F/A in 4/35 (11%), serotype 1 in 1/35 (3%), and serotype 6A also in 1/35 (3%).
      CONCLUSIONS: PCR testing demonstrated that the vast majority (97%) of S.
      pneumoniae parapneumonic effusions were caused by serotypes present in the 13
      serotype vaccine that were not present in the original 7 serotype vaccine. This
      suggests that use of the 13-serotype vaccine could potentially prevent many S.
      pneumoniae pneumonias complicated by parapneumonic effusion in our region,
      provided serotype replacement does not occur.

PMID- 25060940
TI  - Successful perioperative use of prothrombin complex concentrate in the treatment
      of acquired factor X deficiency in the setting of systemic light-chain (AL)
      amyloidosis.

PMID- 25060941
TI  - A data-driven approach to prostate cancer detection from dynamic contrast
      enhanced MRI.
AB  - Magnetic resonance imaging (MRI), particularly dynamic contrast enhanced (DCE)
      imaging, has shown great potential in prostate cancer diagnosis and staging. In
      the current practice of DCE-MRI, diagnosis is based on quantitative parameters
      extracted from the series of T1-weighted images acquired after the injection of a
      contrast agent. To calculate these parameters, a pharmacokinetic model is fitted
      to the T1-weighted intensities. Most models make simplistic assumptions about the
      perfusion process. Moreover, these models require accurate estimation of the
      arterial input function, which is challenging. In this work we propose a data
      driven approach to characterization of the prostate tissue that uses the time
      series of DCE T1-weighted images without pharmacokinetic modeling. This approach
      uses a number of model-free empirical parameters and also the principal component
      analysis (PCA) of the normalized T1-weighted intensities, as features for cancer
      detection from DCE MRI. The optimal set of principal components is extracted with
      sparse regularized regression through least absolute shrinkage and selection
      operator (LASSO). A support vector machine classifier was used with leave-one
      patient-out cross validation to determine the ability of this set of features in
      cancer detection. Our data is obtained from patients prior to radical
      prostatectomy and the results are validated based on histological evaluation of
      the extracted specimens. Our results, obtained on 449 tissue regions from 16
      patients, show that the proposed data-driven features outperform the traditional
      pharmacokinetic parameters with an area under ROC of 0.86 for LASSO-isolated PCA
      parameters, compared to 0.78 for pharmacokinetic parameters. This shows that our
      novel approach to the analysis of DCE data has the potential to improve the
      multiparametric MRI protocol for prostate cancer detection. 

PMID- 25060942
TI  - Blue luminescence of dendrimer-encapsulated gold nanoclusters.
AB  - Direct evidence for the blue luminescence of gold nanoclusters encapsulated
      inside hydroxyl-terminated polyamidoamine (PAMAM) dendrimers was provided by
      spectroscopic studies as well as by theoretical calculations. Steady-state and
      time-resolved spectroscopic studies showed that the luminescence of the gold
      nanoclusters consisted largely of two electronic transitions. Theoretical
      calculations indicate that the two transitions are attributed to the different
      sizes of the gold nanoclusters (Au8 and Au13). The luminescence of the gold
      nanoclusters was clearly distinguished from that of the dendrimers.

PMID- 25060943
TI  - The Global Online Sexuality Survey (GOSS): male homosexuality among Arabic
      speaking internet users in the Middle East--2010.
AB  - INTRODUCTION: The prevalence of male homosexuality is difficult to elicit
      considering the sensitivity of one's sexual orientation. The Global Online
      Sexuality Survey (GOSS) is an online epidemiologic study of male and female
      sexuality. The online nature of GOSS allows more confidentiality and wider
      geographic reach, particularly important in investigating sexual issues within
      the more conservative societies. AIM: This study aims to determine the prevalence
      of male homosexuality among Internet users in the Arabic-speaking Middle East and
      the unique characteristics of this subset of the population. MAIN OUTCOME
      MEASURES: Prevalence of male homosexuality. METHODS: In the year 2010, GOSS was
      offered to Arabic-speaking web surfers above 18 years of age in the Middle East.
      Potential participants were invited via advertising on Facebook(r). Invitations
      were dispatched randomly with the exception of geographic region and age,
      regardless web surfing preferences. GOSS relied in part on validated
      questionnaires such as the International Index of Erectile Function, as well on
      other nonvalidated questions. RESULTS: 17.1% reported desire toward the same sex,
      of whom 5.6% had homosexual encounters, mostly in the form of external
      stimulation rather than intercourse, and exclusively undercover. An overwhelming
      majority was ego-dystonic (78.2%). CONCLUSION: This is--to our knowledge--the
      first online survey to address the prevalence of homosexual orientation and
      practice in the Middle East, discriminating desire from practice, ego-syntonic
      from ego-dystonic, and investigating the pattern of practice. Homosexual desire
      is present in the Middle East as it is around the world, and homosexual
      encounters are as prevalent. Yet, the undercover and ego-dystonic states prevail.

PMID- 25060944
TI  - Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the
      ventromedial prefrontal cortex.
AB  - Endocrine signals such as ghrelin and leptin are known to modulate the
      mesocorticolimbic dopaminergic system and, consequently, show associations with
      food and drug reward. In animal models, nicotine was demonstrated to reduce body
      weight by attenuating food intake and effects of leptin and ghrelin are partly
      modulated by nicotinic acetylcholine receptors which hint at potential
      interactions. However, the neuropharmacological modulation of endocrine signals
      by nicotine in healthy humans remains to be tested experimentally. We used
      functional magnetic resonance imaging to investigate food-cue reactivity after an
      overnight fast and following a caloric load (oral glucose tolerance test, OGTT)
      in 26 healthy normal-weight never-smokers. Moreover, we administered either
      nicotine (2 mg) or placebo gums using a randomized cross-over design and assessed
      blood plasma levels of ghrelin and leptin. During fasting, nicotine
      administration decreased correlations with ghrelin levels in the
      mesocorticolimbic system whereas correlations with leptin were increased. After
      the OGTT, nicotine increased the modulatory effects of ghrelin and leptin on food
      cue reactivity, particularly in the ventromedial prefrontal cortex (vmPFC) and
      the amygdala. Critically, this led to an indirect modulation of the behavioral
      'appetizer effect' (i.e. cue-induced increases in subjective appetite) by
      homeostatic feedback signals via food-cue reactivity in vmPFC. We conclude that
      nicotine enhances the effect of ghrelin and leptin in the valuation and relevance
      network which might, in turn, reduce appetite. This highlights that amplifying
      the impact of homeostatic signals such as ghrelin and leptin in normal-weight
      individuals might hint at a mechanism contributing to nicotine's anorexic
      potential.

PMID- 25060945
TI  - Cytotoxic activity of octahydropyrazin[2,1-a:5,4-a']diisoquinoline derivatives in
      human breast cancer cells.
AB  - Evaluation of the cytotoxicity of novel octahydropyrazin[2,1-a:5,4
      a']diisoquinoline derivatives (1a-2c) employing a 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay and inhibition of [(3)H]thymidine
      incorporation into DNA demonstrated that these compounds were more active than
      etoposide and camptothecin in both MDA-MB-231 and MCF-7 human breast cancer
      cells. Flow cytometric analysis after Annexin V-FITC and propidium iodide
      staining also confirmed that apoptosis was the main response of human breast
      cancer cells to 1a-2c treatment. Our results suggest that apoptosis of human
      breast cancer cells in the presence of 1a-2c follows the mitochondrial pathway,
      with the decrease in mitochondrial membrane potential and activation of caspase
      9, as well as by the external pathway with the significant increase in caspase 8
      expression. Cytotoxic properties of compounds 1a-2c in cultured human breast
      cancer cells correlate to their ability to inhibit topoisomerase I/II. 

PMID- 25060946
TI  - Efficacy and safety of olmesartan medoxomil/amlodipine fixed-dose combination for
      hypertensive patients uncontrolled with monotherapy.
AB  - This study aimed to evaluate the efficacy and safety of olmesartan medoxomil
      (OM)/amlodipine (AML) 20/5 mg fixed-dose combination tablet in Chinese mild to
      moderately hypertensive patients with inadequate blood pressure (BP) control on
      monotherapy. Two multicenter, randomized, double-blind, double-dummy, active
      controlled, parallel group clinical trials were conducted. After screening and a
      2-week placebo run-in period, patients with 95 mmHg <= seated diastolic blood
      pressure (SeDBP) < 110 mmHg received monotherapy with OM 20 mg (in Study 1) or
      AML 5 mg (in Study 2), once daily for 4 weeks. Patients with 90 mmHg <= mean
      SeDBP < 110 mmHg at the end of the monotherapy period were randomized to receive
      OM/AML 20/5 mg treatment or continue with the monotherapy, once daily for 8
      weeks. OM/AML (20/5 mg) treatment significantly lowered both systolic and
      diastolic BP at 4 and 8 weeks compared to 40 mg olmesartan or 5 mg AML. The
      incidence of drug-related adverse effects did not differ significantly between
      the groups. OM/AML 20/5 mg was superior to OM 40 mg or AML 5 mg monotherapy in
      lowering BP in Chinese mild to moderately hypertensive patients with inadequate
      BP control on monotherapy. No new or unexpected safety issues were identified
      with OM/AML combination therapy compared to monotherapy.

PMID- 25060947
TI  - Two new sesquiterpenoids from endophytic fungus J3 isolated from Mangrove Plant
      Ceriops tagal.
AB  - Two new sesquiterpenoids, named 2alpha-hydroxyxylaranol B (1) and 4beta
      hydroxyxylaranol B (2), together with a known diterpenoid 3,4-seco-sonderianol
      (3) were isolated from the fermentation of endophytic fungus J3 of Ceriops tagal.
      Their structures were elucidated based on spectroscopic methods including 1D and
      2D NMR (HMQC, (1)H-(1)H COSY and HMBC). All compounds were evaluated for their
      cytotoxic activities by MTT method, and compound 3 exhibited cytotoxic activities
      against K562, SGC-7901, and BEL-7402 cell lines. 

PMID- 25060948
TI  - Effects of age increase on hepatic expression and activity of cytochrome P450 in
      male C57BL/6 mice.
AB  - Effects of aging on hepatic expression and activity of cytochrome P450 (CYP)
      isoforms were investigated in male mice aged 2, 6, 18, and 30 months. Microsomal
      protein, total CYP, cytochrome b5 and NADPH-dependent cytochrome P450 reductase
      contents in liver were fully expressed in young (2-month-old) mice. Neither
      Cyp1a1 nor Cyp2c was detected in any aged mice. And Cyp1a2 was maximally
      expressed at 2 months and decreased with age. Hepatic levels of Cyp2b10 and
      Cyp3a11 were decreased in 30-month-old mice. Hepatic Cyp2e1 levels were
      constantly maintained from 2-month to 30-month old mice. Hepatic activities of
      ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase were gradually
      decreased after 6 months. The 30-month-old mice exhibited the lowest activity of
      midazolam 1'-hydroxylase. Pentoxyresorufin-O-depenthylase activity was decreased
      in 30-month-old mice, but not statistically significant. There were no
      significant differences in hepatic activities of chlorzoxazone 6-hydroxylase and
      midazolam 4-hydroxylase. The present study shows that increasing age, especially
      30-month-old mice, leads to decrease in expression and activity of hepatic CYP
      isoforms, suggesting that aging mice exhibit poor hepatic drug-metabolizing
      capacity. 

PMID- 25060949
TI  - [Anaesthetic management of Stiff Man syndrome].
AB  - Stiff Man syndrome or stiff-person syndrome is a rare autoimmune disorder. It is
      characterized by increased axial muscular tone and limb musculature, and painful
      spasms triggered by stimulus. The case is presented of a 44-year-old man with
      stiff-person syndrome undergoing an injection of botulinum toxin in the urethral
      sphincter under sedation. Before induction, all the surgical team were ready in
      order to minimise the anaesthetic time. The patient was monitored by continuous
      ECG, SpO2 and non-invasive blood pressure. He was induced with fractional dose of
      propofol 150 mg, fentanyl 50 MUg and midazolam 1mg. Despite careful titration,
      the patient had an O2 saturation level of 90%,which was resolved by manual
      ventilation. There was no muscle rigidity or spasm during the operation. Post
      operative recovery was uneventful and the patient was discharged 2 days later. A
      review of other cases is presented. The anaesthetic concern in patients with
      stiff-person syndrome is the interaction between the anaesthetic agents, the
      preoperative medication, and the GABA system. For a safe anaesthetic management,
      total intravenous anaesthesia is recommended instead of inhalation anaesthetics,
      as well as the close monitoring of the respiratory function and the application
      of the electrical nerve stimulator when neuromuscular blockers are used.

PMID- 25060950
TI  - Single shot spinal anesthesia with very low hyperbaric bupivacaine dose (3.75 mg)
      for hip fracture repair surgery in the elderly. A randomized, double blinded
      study.
AB  - PURPOSE: Single shot spinal anesthesia is used worldwide for hip fracture repair
      surgery in the elderly. Arterial hypotension is a frequent adverse effect. We
      hypothesized that lowering local anesthetics dose could decrease the incidence of
      arterial hypotension, while maintaining quality of surgical anesthesia. METHODS:
      In a randomized double blinded study, 66 patients over the age of 65 years, with
      hip fracture needing surgical repair, were assigned to B0.5 group 7.5mg
      hyperbaric bupivacaine 5mg/ml (control group), and B0.25 group 3.75mg hyperbaric
      bupivacaine 2.5mg/ml (study group). Sensory and motor block level, and
      hemodynamic parameters including blood presure, heart rate and vasopressor dose
      administration were registered, along with rescue anesthesia needs, the
      feasibility of surgery, its duration, and regression time of sensory anesthesia
      to T12. RESULTS: After exclusions, 61 patients were included in the final
      analysis. Arterial hypotension incidence was lower in the B0.25 group (at the 5,
      10, and 15min determinations), and a lower amount of vasopressor drugs was needed
      (mean accumulated ephedrine dose 1.6mg vs. 8.7mg in the B0.5 group, p<0.002).
      Sensory block regression time to T12 was shorter in the B0.25 group, mean 78.6+/
      23.6 (95% CI 51.7-110.2)min vs. 125.5+/-37.9 (95% CI 101.7-169.4)min in the B0.5
      group, p=0.033. All but one patient in the B0.25 group were operated on under the
      anesthetic procedure first intended. No rescue anesthesia was needed. CONCLUSION:
      Lowering bupivacaine dose for single shot spinal anesthesia for hip fracture
      repair surgery in elderly patients was effective in decreasing the occurrence of
      arterial hypotension and vasopressor use, while intraoperative quality remained.

PMID- 25060951
TI  - Patterns of genetic diversity in the polymorphic ground snake (Sonora
      semiannulata).
AB  - We evaluated the genetic diversity of a snake species with color polymorphism to
      understand the evolutionary processes that drive genetic structure across a large
      geographic region. Specifically, we analyzed genetic structure of the highly
      polymorphic ground snake, Sonora semiannulata, (1) among populations, (2) among
      color morphs (3) at regional and local spatial scales, using an amplified
      fragment length polymorphism dataset and multiple population genetic analyses,
      including FST-based and clustering analytical techniques. Based upon these
      methods, we found that there was moderate to low genetic structure among
      populations. However, this diversity was not associated with geographic locality
      at either spatial scale. Similarly, we found no evidence for genetic divergence
      among color morphs at either spatial scale. These results suggest that despite
      dramatic color polymorphism, this phenotypic diversity is not a major driver of
      genetic diversity within or among populations of ground snakes. We suggest that
      there are two mechanisms that could explain existing genetic diversity in ground
      snakes: recent range expansion from a genetically diverse founder population and
      current or recent gene flow among populations. Our findings have further
      implications for the types of color polymorphism that may generate genetic
      diversity in snakes. 

PMID- 25060952
TI  - Unconditional and conditional QTL analysis of kernel weight related traits in
      wheat (Triticum aestivum L.) in multiple genetic backgrounds.
AB  - Wheat thousand kernel weight (TKW) is a complex trait, and is largely controlled
      by several kernel traits, including kernel length (KL) and kernel width (KW). In
      order to reveal the genetic relationship between TKW and these kernel traits (KW
      and KL) as accurate as possible, we applied both unconditional and conditional
      mapping analyses to three distinct genetic populations, one DH population and two
      RIL populations. This report describes the identifications of 36 unconditional
      and conditional additive QTLs and 30 pairs of unconditional and conditional
      epistatic QTLs, all of which are closely associated with TKW. While the
      conditional additive locus Qtkw1B, detected in the RIL2 population, exhibited the
      largest contribution, explaining 14.12 % of TKW variance, the unconditional
      epistatic QTLs Qtkw3A-2/Qtkw5B.1, detected in the DH population, accounted for
      11.95 % of phenotypic variance. This study also showed that, compared with
      unconditional mapping, conditional mapping resulted in very different numbers and
      different extent of effects of additive and epistatic QTLs that were associated
      with TKW when TKW was conditioned on kernel traits (KW and KL). These data
      strongly suggest that KW and KL indeed play a significant role in determining
      TKW. Furthermore, we demonstrated that the effects of the 25 additive QTLs for
      TKW were either entirely or largely determined by KW, while the effects of the
      other 25 additive QTLs for TKW were either entirely or largely affected by KL. We
      conclude that the conditional mapping can be useful for a better understanding of
      the interrelationship between the yield contributing traits at the QTL level. 

PMID- 25060953
TI  - Remarkable luminescence enhancement of chloroplatinum(II) complexes of
      hexaethylene glycol methyl ether substituted 2,6-bis(benzimidazol-2'-yl)pyridine
      in water triggered by PF6-.
AB  - Three chloroplatinum(II) complexes of 2,6-bis(benzimidazol-2'-yl)pyridine bearing
      hexaethylene glycol methyl ether are almost nonemissive in dilute aqueous
      solutions. Upon addition of excessive hexafluorophosphate salts to their dilute
      aqueous solutions, one of them was found to show a remarkable luminescence
      enhancement.

PMID- 25060955
TI  - Influence of fear-avoidance beliefs on disability in patients with subacromial
      shoulder pain in primary care: a secondary analysis.
AB  - BACKGROUND: Little information exists about the role of fear-avoidance beliefs
      and catastrophizing in subacromial pain syndrome. OBJECTIVE: The purpose of this
      study was to investigate the associations among pain, catastrophizing, fear, and
      disability and the contribution of fear-avoidance beliefs to disability at
      baseline and at 3-month follow-up. DESIGN: A cross-sectional and longitudinal
      analysis was conducted. METHODS: Baseline demographic and clinical data,
      including fear-avoidance beliefs and catastrophizing, of 90 patients were
      assessed for this analysis. Disability was measured with the Shoulder Pain and
      Disability Index at baseline and at 3-month follow-up. First, bivariate and
      partial correlations were calculated among pain, fear-avoidance beliefs,
      catastrophizing, and disability, based on the fear-avoidance model. Second, the
      contribution of fear-avoidance beliefs to disability at baseline and at 3-month
      follow-up was examined with hierarchical regression analyses. RESULTS:
      Correlations between clinical variables and disability were largely in line with
      the fear-avoidance model. Regression analyses identified a significant
      contribution of fear-avoidance beliefs to baseline disability but not to
      disability at 3 months. LIMITATIONS: Patients with subacromial pain syndrome were
      studied; therefore, the results should be transferred with caution to other
      diagnoses. A modified version of the Fear-Avoidance Beliefs Questionnaire was
      used, which was not validated for this patient group. CONCLUSIONS: Fear-avoidance
      beliefs contribute significantly to baseline disability but not to disability
      change scores after 3-month follow-up. Duration of complaints and baseline
      disability were the main factors influencing disability change scores. Although
      the results help to improve understanding of the role of fear-avoidance beliefs,
      further studies are needed to fully understand the influence of psychological and
      clinical factors on the development of disability in patients with subacromial
      shoulder pain.

PMID- 25060954
TI  - Salt-inducible kinase 3, SIK3, is a new gene associated with hearing.
AB  - Hearing function is known to be heritable, but few significant and reproducible
      associations of genetic variants have been identified to date in the adult
      population. In this study, genome-wide association results of hearing function
      from the G-EAR consortium and TwinsUK were used for meta-analysis. Hearing
      ability in eight population samples of Northern and Southern European ancestry (n
      = 4591) and the Silk Road (n = 348) was measured using pure-tone audiometry and
      summarized using principal component (PC) analysis. Genome-wide association
      analyses for PC1-3 were conducted separately in each sample assuming an additive
      model adjusted for age, sex and relatedness of subjects. Meta-analysis was
      performed using 2.3 million single-nucleotide polymorphisms (SNPs) tested against
      each of the three PCs of hearing ability in 4939 individuals. A single SNP lying
      in intron 6 of the salt-inducible kinase 3 (SIK3) gene was found to be associated
      with hearing PC2 (P = 3.7*10(-8)) and further supported by whole-genome sequence
      in a subset. To determine the relevance of this gene in the ear, expression of
      the Sik3 protein was studied in mouse cochlea of different ages. Sik3 was
      expressed in murine hair cells during early development and in cells of the
      spiral ganglion during early development and adulthood. Our results suggest a
      developmental role of Sik3 in hearing and may be required for the maintenance of
      adult auditory function. 

PMID- 25060956
TI  - Perceived exercise barriers explain exercise participation in Australian women
      treated for breast cancer better than perceived exercise benefits.
AB  - OBJECTIVES: This study aimed to determine the effect of perceived exercise
      benefits and barriers on exercise levels among women who have been treated for
      breast cancer and have not participated in a formal exercise intervention.
      DESIGN: This was an anonymous, national, online cross-sectional survey study.
      METHODS: Four hundred thirty-two women treated for breast cancer completed an
      online survey covering their treatment and demographic background, current
      exercise levels, and perceived exercise benefits and barriers. Each perceived
      benefit and barrier was considered in a binary logistic regression against
      reported exercise levels to ascertain significant relationships and associative
      values (odds ratio [OR]). RESULTS: Agreement with 16 out of 19 exercise barriers
      was significantly related to being more likely to report insufficient exercise
      levels, whereas agreement with 6 out of 15 exercise benefits was significantly
      related to being less likely to report insufficient levels of exercise. Feeling
      too weak, lacking self-discipline, and not making exercise a priority were the
      barriers with the largest association to insufficient exercise levels (OR=10.97,
      95% confidence interval [CI]=3.90, 30.86; OR=8.12, 95% CI=4.73, 13.93; and
      OR=7.43, 95% CI=3.72, 14.83, respectively). Conversely, exercise enjoyment,
      improved feelings of well-being, and decreased feelings of stress and tension
      were the top 3 benefits associated with being less likely to have insufficient
      exercise levels (OR=0.21, 95% CI=0.11, 0.39; OR=0.21, 95% CI=0.07, 0.63; and
      OR=0.31, 95% CI=0.15, 0.63, respectively). LIMITATIONS: Self-reported data
      measures were used to collect exercise data. CONCLUSIONS: Targeting exercise
      barriers specific to women treated for breast cancer may improve exercise
      participation levels in this cohort. Awareness of the impact of exercise barriers
      identified in the present study will enable physical therapists to better plan
      exercise interventions that support all women treated for breast cancer.

PMID- 25060957
TI  - Rehabilitation therapies after botulinum toxin-A injection to manage limb
      spasticity: a systematic review.
AB  - BACKGROUND: Botulinum toxin A (BoNT-A) injections are increasingly used to treat
      muscle spasticity and are often complemented by adjunctive rehabilitation
      therapies; however, little is known about the effect of therapy after injection.
      PURPOSE: The aim of this study was to identify and summarize evidence on
      rehabilitation therapies used after BoNT-A injections to improve motor function
      in adults with neurological impairments. DATA SOURCES: Searches were conducted in
      PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL,
      National Research Register, metaRegistry of Controlled Trials, PEDro, and
      OTseeker. STUDY SELECTION: Randomized and quasi-randomized controlled trials were
      considered for inclusion. Participants with neurological impairments received
      BoNT-A to treat focal spasticity in limbs, with rehabilitation interventions
      provided to experimental groups only. Primary outcome measures were joint
      mobility, function of the affected limb, and spasticity. Eleven studies with 234
      participants, most of whom had stroke, were included in the review. DATA
      EXTRACTION: Two reviewers extracted study details and data. DATA SYNTHESIS:
      Methodological quality was rated using the PEDro scale. Both fixed-effects and
      random-effects models were used to calculate effect size. RESULTS: Studies were
      of variable quality: 3 were poor (PEDro score 1 to 4), and 8 were moderate (PEDro
      score 6 to 7). No study investigated effects for longer than 24 weeks (6 months).
      Included trials presented 9 therapy types, including ergometer cycling,
      electrical stimulation, stretch (casting, splinting, taping, or manual or
      exercise-induced stretch), constraint-induced movement therapy, task-specific
      motor training, and exercise programs. Statistical findings suggest that combined
      therapy and BoNT-A is slightly more effective than BoNT-A alone. CONCLUSION:
      Evidence relating to impact of adjunct therapy is available, but the
      heterogeneity of studies limits the opportunity to demonstrate overall impact.
      Researchers need to consider the benefits of greater consistency in study
      approaches and measures so that meaningful evaluations of overall adjunct therapy
      effects can be made.

PMID- 25060958
TI  - Assessment of glenohumeral subluxation in poststroke hemiplegia: comparison
      between ultrasound and fingerbreadth palpation methods.
AB  - BACKGROUND: Glenohumeral subluxation (GHS) is a common poststroke complication.
      Treatment of GHS is hampered by the lack of objective, real-time clinical
      measurements. OBJECTIVE: The aims of this study were: (1) to compare an
      ultrasound method of GHS measurement with the fingerbreadth palpation method
      using a receiver operating characteristic curve (ROC) and (2) to report the
      sensitivity and specificity of this method. DESIGN: A prospective study was
      conducted. SETTING: The study was conducted in local hospitals and day centers in
      the southwest of England. PATIENTS: One hundred five patients who had one-sided
      weakness following a first-time stroke (51 men, 54 women; mean age=71 years,
      SD=11) and who gave informed consent were enrolled in the study. MEASUREMENTS:
      Ultrasound measurements of acromion-greater tuberosity (AGT) distance were used
      for the assessment of GHS. Measurements were undertaken on both shoulders by a
      research physical therapist trained in shoulder ultrasound with the patient
      seated in a standardized position. Fingerbreadth palpation assessment of GHS was
      undertaken by a clinical physical therapist based at the hospital, who also
      visited the day centers. RESULTS: The area under the ROC curve was 0.73 (95%
      confidence interval [95% CI]=0.63, 0.83), suggesting that the ultrasound method
      has good agreement compared with the fingerbreadth palpation method. A cutoff
      point of >=0.2 cm AGT measurement difference between affected and unaffected
      shoulders generated a sensitivity of 68% (95% CI=51%, 75%), a specificity of 62%
      (95% CI=47%, 80%), a positive likelihood ratio of 1.79 (95% CI=1.1, 2.9), and a
      negative likelihood ratio of 0.55 (95% CI=0.4, 0.8). LIMITATIONS: Clinical
      therapists involved in the routine care of patients conducted the fingerbreadth
      palpation method. It is likely that they were aware of the patients' subluxation
      status. CONCLUSION: The ultrasound method can detect minor asymmetry (<=0.5 cm)
      and has the potential advantage over the fingerbreadth palpation method of
      identifying patients with minor subluxation.

PMID- 25060959
TI  - The contribution of conceptual frameworks to knowledge translation interventions
      in physical therapy.
AB  - There is growing recognition of the importance of knowledge translation
      activities in physical therapy to ensure that research findings are integrated
      into clinical practice, and increasing numbers of knowledge translation
      interventions are being conducted. Although various frameworks have been
      developed to guide and facilitate the process of translating knowledge into
      practice, these tools have been infrequently used in physical therapy knowledge
      translation studies to date. Knowledge translation in physical therapy implicates
      multiple stakeholders and environments and involves numerous steps. In light of
      this complexity, the use of explicit conceptual frameworks by clinicians and
      researchers conducting knowledge translation interventions is associated with a
      range of potential benefits. This perspective article argues that such frameworks
      are important resources to promote the uptake of new evidence in physical
      therapist practice settings. Four key benefits associated with the use of
      conceptual frameworks in designing and implementing knowledge translation
      interventions are identified, and limits related to their use are considered. A
      sample of 5 conceptual frameworks is evaluated, and how they address common
      barriers to knowledge translation in physical therapy is assessed. The goal of
      this analysis is to provide guidance to physical therapists seeking to identify a
      framework to support the design and implementation of a knowledge translation
      intervention. Finally, the use of a conceptual framework is illustrated through a
      case example. Increased use of conceptual frameworks can have a positive impact
      on the field of knowledge translation in physical therapy and support the
      development and implementation of robust and effective knowledge translation
      interventions that help span the research-practice gap. 

PMID- 25060960
TI  - Quorum-quenching activity of the AHL-lactonase from Bacillus licheniformis DAHB1
      inhibits Vibrio biofilm formation in vitro and reduces shrimp intestinal
      colonisation and mortality.
AB  - Vibrio parahaemolyticus is a significant cause of gastroenteritis resulting from
      the consumption of undercooked sea foods and often cause significant infections
      in shrimp aquaculture. Vibrio virulence is associated with biofilm formation and
      is regulated by N-acylated homoserine lactone (AHL)-mediated quorum sensing. In
      an attempt to reduce vibrio colonisation of shrimps and mortality, we screened
      native intestinal bacilli from Indian white shrimps (Fenneropenaeus indicus) for
      an isolate which showed biofilm-inhibitory activity (quorum quenching) against
      the pathogen V. parahaemolyticus DAHP1. The AHL-lactonase (AiiA) expressed by one
      of these, Bacillus licheniformis DAHB1, was characterised as having a broad
      spectrum AHL substrate specificity and intrinsic resistance to the acid
      conditions of the shrimp intestine. Purified recombinant AiiA inhibited vibrio
      biofilm development in a cover slip assay and significantly attenuated infection
      and mortality in shrimps reared in a recirculation aquaculture system.
      Investigation of intestinal samples also showed that AiiA treatment also reduced
      vibrio viable counts and biofilm development as determined by confocal laser
      scanning microscopy (CLSM) imaging. These findings suggest that the B.
      licheniformis DAHB1 quorum-quenching AiiA might be developed for use as a
      prophylactic treatment to inhibit or reduce vibrio colonisation and mortality of
      shrimps in aquaculture. 

PMID- 25060961
TI  - Using conditioned suppression to investigate compulsive drug seeking in rats.
AB  - BACKGROUND: Persistent drug seeking despite harmful consequences is a defining
      characteristic of addiction. Recent preclinical studies have demonstrated the
      occurrence of this hallmark feature of addictive behaviour in rodents. For
      example, it has been shown that the ability of an aversive conditioned stimulus
      (CS) to suppress cocaine seeking was diminished after an extended self
      administration history. The present study aimed to optimize the experimental
      conditions to examine conditioned suppression of sucrose and cocaine seeking in
      rats, and its dependence on the longevity of self-administration experience.
      METHODS: We investigated whether conditioned suppression depends on the intensity
      and quantity of footshocks during conditioning. In addition, the effects of CS
      omission, extinction and reconditioning were investigated, as well as the
      influence of the CS interval sequence on conditioned suppression. We also
      compared conditioned suppression after a limited and extended sucrose or cocaine
      self-administration history. RESULTS: We found that conditioned suppression
      depended on the intensity rather than the quantity of footshocks, whereby a
      higher footshock intensity was necessary to induce suppression of cocaine seeking
      compared to sucrose seeking. Conditioned suppression was most pronounced when the
      test started with presentation of the aversive CS, and conditioned suppression
      could be extinguished and reacquired. In addition, conditioned suppression of
      cocaine, but not sucrose seeking was reduced after extended self-administration
      experience. CONCLUSIONS: These data provide a detailed analysis of conditioned
      suppression of cocaine and sucrose seeking. Importantly, we confirm the
      usefulness of conditioned suppression to study persistent drug seeking after
      prolonged drug self-administration.

PMID- 25060963
TI  - Short-term storage evaluation of quality and antioxidant capacity in chestnut
      wheat bread.
AB  - BACKGROUND: Bread traditionally made from wheat is now often supplemented with
      alternative functional ingredients as chestnut flours; no data have been
      previously published about the staling of chestnut-containing bread. Thus short
      term storage (3 days) for chestnut flour-supplemented soft wheat bread is
      evaluated by means of selected physicochemical properties (i.e. water dynamics,
      texture, colour, crumb grain characteristic, total antioxidant capacity).
      RESULTS: Bread prepared with a 20:80 ratio of chestnut:soft wheat flours
      maintained its moisture content in both crust and crumb. Crumb hardness, after
      baking, was found to be significantly higher than that of the soft wheat bread;
      it did not change during storage, whereas it significantly increased in the
      control bread until the end of the shelf life. The supplemented bread presented a
      heterogeneous crumb structure, with a significant decrease in the largest pores
      during shelf life, relative to the shrinkage of crumb grain. The control
      exhibited a significant redistribution of crumb holes, with a decrease in the
      smallest grain classes and an increase in the intermediate ones, most likely
      caused by cell wall thickening. The colour of the crumb remained unaltered in
      both breads. The crust of the control presented a significant decrease of a*
      (redness) and that of the supplemented bread exhibited a decrease of b*
      (yellowness). The antioxidant capacity was detected after day 1 of storage in the
      chestnut flour bread only. CONCLUSION: Chestnut flour supplementation could
      represent a feasible way of producing bread with improved characteristics, not
      only just after baking but also during shelf life.

PMID- 25060962
TI  - Determinants of waterpipe smoking initiation among school children in Irbid,
      Jordan: a 4-year longitudinal analysis.
AB  - OBJECTIVE: Guided by the Attitude-Social influence-self Efficacy (ASE) theory,
      this study identified predictors of waterpipe (WP) smoking initiation in a WP
      naive cohort of Jordanian school children. METHODS: A school-based cohort of all
      7th grade students (N=1781) in 19 of 60 schools in Irbid, Jordan, was followed
      from 2008 to 2011. Generalized linear mixed modeling was used to examine
      predictors of WP initiation among WP-naive students (N=1243). RESULTS: During the
      3-year study, WP initiation was documented in 39% of boys and 28% of girls. Prior
      cigarette smoking (boys: odds ratio 7.41; 95% confidence interval 4.05-12.92 and
      girls: 8.48; 4.34-16.56) and low WP refusal self-efficacy (boys: 26.67; 13.80
      51.53 and girls: 11.49; 6.42-20.55) were strongly predictive of initiating WP.
      Boys were also more likely to initiate WP smoking if they had siblings (2.30;
      1.14-4.64) or teachers (2.07; 1.12-3.84) who smoked and girls if they had friends
      (2.96; 1.59-5.54) who smoked. CONCLUSION: There is a sizeable incidence of WP
      initiation among students of both sexes. These findings will help in designing
      culturally responsive prevention interventions against WP smoking. Gender
      specific factors, refusal skills, and cigarette smoking need to be important
      components of such initiatives.

PMID- 25060964
TI  - Biliary complications in living donor right hepatectomy are affected by the
      method of bile duct division.
AB  - The bile duct division is a crucial step in the donor hepatectomy. Multiple small
      ducts will make the biliary reconstruction more difficult and may influence the
      outcome of the recipient. Biliary leakage, bilomas and biliary strictures are
      well recognized donor complications that may be directly linked to bile duct
      division. Biliary division still needs more standardization. This work aims to
      analyze our experience with two different methods of bile duct division in
      relation to the development of intraoperative and postoperative biliary
      complications. Between April 2004 and March 2013, 216 liver donors underwent
      right hepatectomy, in Gastro-Enterology Surgical Center, Mansoura University,
      Egypt. According to the method of bile duct division, the study population was
      divided into 2 groups; 1- extrahepatic dissection group (EDG) and 2- fluoroscopy
      guided transection group (FGG), each comprised 108 patients. Data were collected
      from a prospectively registered database, with special emphasis on the occurrence
      of biliary complications. Complications were classified according to the latest
      version of Clavien classification. Intraoperative biliary complications did not
      differ between both groups, p = 0.313. The commonest postoperative complication
      was biliary leak/biloma accounting for 32.5% of all donor complications, followed
      by non-biliary fluid collections. 24 (11.1%) donors developed 27 biliary
      complications. The FGG showed significantly less biliary complications (5.6%, 6
      donors), when compared to EDG (15.7%, 18 donors), p = 0.015. Grade 3
      complications were significantly higher in EDG, p = 0.024. On multivariate
      analysis, the only significant factor predicting the occurrence of biliary
      complications was the use of fluoroscopy guided bile duct division, p = 0.009. In
      conclusion, we believe that the proposed method of biliary division is safe,
      simple and reproducible.

PMID- 25060965
TI  - The protective effect of Borago Officinalis extract on amyloid beta (25-35)
      induced long term potentiation disruption in the dentate gyrus of male rats.
AB  - Alzheimer's disease (AD) begins with impairment in synaptic functions before
      developing into later neurodegeneration and neural loss. In the present study we
      have examined the protective effects of Borago Officinalis (borage) extract on
      amyloid beta (Abeta)--Induced long term potentiation (LTP) disruption in
      hippocampal dentate gyrus (DG). Wistar male rats received intrahippocampal (IHP)
      injection of the Abeta (25-35) and borage extract throughout gestation (100
      mg/kg). LTP in perforant path- DG synapses was assessed using electrophysiology
      method and field excitatory post- synaptic potential (fEPSP) slope and population
      spike (PS) amplitude were measured by 400 Hz tetanization. Finally, the total
      thiol content of hippocampus was measured using colorimetric reaction based on
      the Ellman's method. The results showed that Abeta (25-35) significantly
      decreased fEPSP slope and SP amplitude comparing with the control and sham group,
      whereas borage extract administration increased these parameters compared to the
      Abeta group. Abeta induced a remarkable decrease in total thiol content of
      hippocampus and borage prevented the decrease of the hippocampal total sulfhydryl
      (SH) groups. This data suggest that Abeta (25-35) can effectively inhibit LTP in
      the granular cells of the DG in hippocampus, and borage supplementation reverse
      the synaptic plasticity in DG following Abeta treatment and that borage
      consumption may lead to an improvement of AD-induced cognitive dysfunction.

PMID- 25060966
TI  - Brain glycogen--vestigial no more. Foreword.

PMID- 25060967
TI  - Effects of different etomidate doses on intraoperative somatosensory-evoked
      potential monitoring.
AB  - BACKGROUND: Somatosensory-evoked potentials (SSEPs) are widely used for
      intraoperative spinal cord monitoring. Although many general anesthetics inhibit
      SSEPs, etomidate has been reported to boost SSEPs. This clinical study aimed to
      test whether etomidate doses less than 0.3 mg/kg amplify SSEP monitoring.
      METHODS: Patients were divided into four groups: A, B, C, and D. Etomidate doses
      of 0.1, 0.2, and 0.3 mg/kg were infused into patients in groups A, B, and C,
      respectively, after baseline SSEPs were obtained. Group D patients were infused
      with saline. In the subsequent 15 min, the amplitudes and latencies of SSEPs were
      recorded and compared. RESULTS: Etomidate exhibited amplification effects on
      SSEPs, and this effect increased with dose escalation. The amplitude changes in
      groups A, B, and C were significantly different (P = 0.002, P = 0.000, and P =
      0.000, respectively) from that of group D. The amplitude change was largest in
      group C and significantly greater than those in groups A and B (P = 0.006, P =
      0.000). Latency was not significantly affected (P < 0.05) by etomidate.
      CONCLUSION: Small doses of etomidate that were less than 0.3 mg/kg had dose
      related amplification effects on SSEP monitoring.

PMID- 25060968
TI  - Sleep-wake disturbance in interepisode bipolar disorder and high-risk
      individuals: a systematic review and meta-analysis.
AB  - Over the past decade, researchers have shifted focus from the manic and
      depressive episodes to the interepisode period in the study of sleep-wake
      disturbance in bipolar disorder. The objective of this systematic review was to
      compile and synthesize studies that employed sleep diary, actigraphy,
      polysomnography, and questionnaires to compare sleep-wake patterns in people with
      interepisode bipolar disorder or high-risk individuals vs. normal controls and/or
      people with primary insomnia. We searched key databases until June 2013. Our
      search identified 21 eligible studies, yielding 24 sleep-wake variables. A total
      of 531 people with interepisode bipolar disorder, 157 high-risk individuals, 678
      normal controls and 67 adults with primary insomnia were evaluated. Using a
      random-effects model, our analyses suggest that adults with interepisode bipolar
      disorder appear worse than normal controls in most variables and comparable to
      adults with primary insomnia in certain aspects. Sleep onset latency, wake after
      sleep onset, and variability of sleep-wake variables were most consistently
      impaired in interepisode bipolar disorder. In comparison with controls, high-risk
      individuals were found to have higher variability in sleep efficiency and lower
      relative amplitude. The findings provide a foundation for the search for
      candidate endophenotypes and the development of novel interventions for bipolar
      disorder. 

PMID- 25060969
TI  - The conundrum of primary snoring in children: what are we missing in regards to
      cognitive and behavioural morbidity?
AB  - Sleep disordered breathing (SDB) is common in children and describes a continuum
      of nocturnal respiratory disturbance from primary snoring (PS) to obstructive
      sleep apnoea (OSA). Historically, PS has been considered benign, however there is
      growing evidence that children with PS exhibit cognitive and behavioural deficits
      equivalent to children with OSA. There are two popular mechanistic theories
      linking SDB with daytime morbidity: hypoxic insult to the developing brain; and
      sleep disruption due to repeated arousals. These theories apply well to OSA, but
      children with PS experience neither hypoxia nor increased arousals when compared
      to non snoring controls. So what are we missing? This review summarises the
      literature examining daytime morbidity in children with PS and discusses the
      current debates surrounding this relationship. Specifically, questions exist as
      to the sensitivity of our standard assessment techniques to measure subtle
      hypoxia and arousal. There is also a suggestion that the association between PS
      and daytime morbidity may not be mediated by nocturnal respiratory disturbance at
      all, but by a number of other comorbid, but perhaps unrelated factors. As
      approximately 70% of children with SDB are diagnosed with PS, but are rarely
      treated, a paradigm shift in the investigation of PS may be required. 

PMID- 25060970
TI  - Direct observation of doping sites in temperature-controlled, p-doped P3HT thin
      films by conducting atomic force microscopy.
AB  - The distribution of dopant sites in doped poly(3-hexylthiophene) (P3HT) thin
      films is characterized using optical absorption, grazing-incidence X-ray
      diffraction, and conducting atomic force microscopy (c-AFM). It is shown that
      dopant sites can be directly observed using c-AFM and that the solution
      temperature dramatically impacts phase separation and conductivity in spin-cast
      films. 

PMID- 25060971
TI  - Molecular epidemiology of Pneumocystis jiroveci in human immunodeficiency virus
      positive and -negative immunocompromised patients in The Netherlands.
AB  - Pneumocystis jiroveci infections can cause pneumocystis pneumonia (PCP) or lead
      to colonization without signs of PCP. Over the years, different genotypes of P.
      jiroveci have been discovered. Genomic typing of P. jiroveci in different
      subpopulations can contribute to unravelling the pathogenesis, transmission and
      spread of the different genotypes. In this study, we wanted to determine the
      distribution of P. jiroveci genotypes in immunocompetent and immunocompromised
      patients in The Netherlands and determine the clinical relevance of these
      detected mutations. A real-time PCR targeting the major surface glycoprotein gene
      (MSG) was used as a screening test for the presence of P. jiroveci DNA. Samples
      positive for MSG were genotyped based on the internal transcribed spacer (ITS)
      and dihydropteroate synthase (DHPS) genes. Of the 595 included bronchoalveolar
      lavage fluid samples, 116 revealed the presence of P. jiroveci DNA. A total of 52
      of the 116 samples were ITS genotyped and 58 DHPS genotyped. The ITS genotyping
      revealed 17 ITS types, including two types that have not been described
      previously. There was no correlation between ITS genotype and underlying disease.
      All ITS- and DHPS-genotyped samples were found in immunocompromised patients. Of
      the 58 DHPS-genotyped samples, 50 were found to be WT. The other eight samples
      revealed a mixed genotype consisting of WT and type 1. The majority of the latter
      recovered on trimethoprim-sulfamethoxazole suggesting no clinical relevance for
      this mutation.

PMID- 25060972
TI  - Molecular screening of carbapenemase-producing Gram-negative strains in Romanian
      intensive care units during a one year survey.
AB  - This is the first study, to our knowledge, performed on a significant number of
      strains (79 carbapenem-resistant Enterobacteriaceae and 84 carbapenem-resistant
      non-fermenting Gram-negative rods, GNRs) isolated from tissue samples taken from
      patients in the intensive care units of two large hospitals in Bucharest,
      Romania, between 2011 and 2012. The results revealed a high prevalence and great
      diversity of carbapenemase genes (CRG), in both fermenting and non-fermenting
      Gram-negative carbapenem-resistant strains. The molecular screening of carbapenem
      resistant GNRs revealed the presence of worldwide-distributed CRGs (i.e. blaOXA
      48 and blaNDM-1 in Enterobacteriaceae and blaOXA-23, blaVIM-4, blaOXA-10-like,
      blaOXA-60-like, blaSPM-like and blaGES-like in non-fermenting GNRs), reflecting
      the rapid evolution and spread of carbapenemase producers, particularly in
      hospitals. Rapid identification of the colonized or infected patients is
      required, as are epidemiological investigations to establish the local or
      imported origin of the respective strains. 

PMID- 25060973
TI  - Bio-Oss((r)) for delayed osseointegration of implants in dogs: a histological
      study.
AB  - We evaluated the effects of Bio-Oss(r) (a natural bone substitute derived from
      the mineral portion of bovine bone) on delayed osseointegration of implants. The
      bilateral third and fourth mandibular premolars of 4 adult, healthy, male and
      female dogs were extracted. We randomly selected 2 extraction sockets in each dog
      to be filled with Bio-Oss(r) (the experimental group); the other 2 extraction
      sockets, which were not treated, served as controls. Dental implants were
      inserted into the alveolar bone of the experimental group and the control group 3
      months after insertion of the Bio-Oss(r). The osteogenic activity in the bone
      around the implants was assessed by evaluating the histological morphology and
      estimating histomorphometric variables at 3 and 6 months after delayed
      implantation. After 3 months, Goldner's trichrome staining analysis showed that
      the rate of content between the bone and the implant and the mineralised area of
      bone around the implant were significantly higher in the experimental group
      (76%(9%) and 69.5% (9.6%), respectively) than those in the control group (56.1%
      (8.2%) and 52.8% (7.3%), respectively, p=0.003 and 0.000). However, the 2 groups
      did not differ significantly at 6 months. Fluorescence microscopy showed that the
      mean rates of mineralisation of the bony tissue around the implant in the
      experimental group at months 3 and 6 were 6.8 (0.4) MUm and 8.4 (0.8) MUm,
      respectively, which were significantly higher than those in the control group
      (p=0.000 and 0.03). These data indicate that putting Bio-Oss(r) into the
      extraction sockets can promote osseointegration after delayed implantation, and
      may be a promising option for clinical use. 

PMID- 25060975
TI  - Safety of the haemostatic agent Surgiflo(r) in excisions of the submandibular
      gland: our experience in 17 cases.
AB  - Excision of the submandibular gland is a common operation. A surgical drain is
      usually inserted into the wound to prevent the formation of a haematoma, but this
      may not be necessary. We retrospectively studied 17 patients whose submandibular
      glands had been excised and haemostasis achieved with Surgiflo(r) (Ethicon,
      Somerville, USA). There were no complications or side effects. Surgiflo(r)
      established good haemostasis, and can safely be used in place of a surgical
      drain.

PMID- 25060974
TI  - Effect of psychological stress on the structure of the temporomandibular joint
      and the expression of MMP-3 and TIMP-3 in the cartilage in rats.
AB  - Our aim was to observe the effects of psychological stress on the structure of
      the temporomandibular joint (TMJ), and to evaluate the expression of matrix
      metallopeptidase-3 (MMP-3) and tissue inhibitor of metalloproteinase-3 (TIMP-3)
      in condylar chondrocytes in rats. The rats were divided into 3 groups of 12
      according to the duration of psychological stress: 3 weeks or 6 weeks, and 6
      weeks of recovery. A fourth group of 12 rats was used as controls. Each rat was
      evaluated by the open-field test and the weight measured. The results confirmed
      psychological stress in 24 of the 36 rats (67%). The tissues of the TMJ were
      stained with haematoxylin and eosin and pathological changes were studied under a
      light microscope. MMP-3 and TIMP-3 expression was investigated using the SP kit.
      The experimental groups showed thinning of articular cartilage, shedding of
      collagen fibres, cracks in the articular discs, and other structural changes that
      were aggravated with time, from three weeks to six weeks. The 6-week recovery
      group showed an improvement in these changes, which indicated the initiation of
      joint repair. The MMP-3 expression rate correlated with the degree of joint
      lesion, while the TIMP-3 rate showed an opposite trend and was highest in the 6
      week recovery group. Our findings clearly indicate that psychological stress may
      play an important part in the development of TMJ diseases in rats; further
      studies should be made to extrapolate the results to other models before clinical
      use. 

PMID- 25060976
TI  - Percutaneous aspiration thrombectomy in treatment of massive pulmonary embolism.
AB  - BACKGROUND: Pulmonary embolism (PE) associated with haemodynamic instability has
      exceedingly high mortality. We describe our experience using percutaneous
      mechanical thrombectomy (PMT) in patients with massive PE and right ventricle
      dysfunction. METHODS: Sixteen patients (11 males and five females; mean age, 55.7
      +/- 8.3 years) with massive PE were treated with PMT. A percutaneous Aspiration
      Device (8 French Aspirex(r) aspiration thrombectomy catheter, Straub Medical,
      Switzerland) was used in all patients. Clinical outcomes, right ventricle and
      pulmonary artery pressures (PAP), thrombus clearance and complications were
      evaluated. RESULTS: Treatment of 16 patients resulted in complete thrombus
      clearance (>= 90%), in 87.5% of the patients and near-complete (50%-90%)
      clearance in 6.3%. Measurements before and after treatment showed a decrease in
      PAP (73 +/- 11 mm Hg to 34 +/- 8 mm Hg, P<.001). The RV/LV ratio decreased from
      1.32 +/- 0.15 to 0.84 +/- 0.13 at follow-up (P<.001). One patient died from
      refractory shock. No cardiovascular deaths or recurrent PE were documented during
      clinical follow-up but one patient demonstrated evidence of mild cor pulmonale.
      CONCLUSIONS: This study demonstrates safety and effectiveness of percutaneous
      mechanical aspiration thrombectomy in patients with massive PE with a large
      thrombus burden.

PMID- 25060977
TI  - Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1
      expression in allergic rhinitis.
AB  - Azelastine was suggested as a supplementary choice of glucocorticoid for the
      control of moderate to severe allergic rhinitis (AR). However, the underlying
      mechanism has not been completely understood. In this study, primary cultured
      nasal epithelial cells and bronchial epithelial cells were stimulated with
      proinflammatory cytokines (IL-1beta and IL-17A) and anti-inflammatory agents
      (azelastine and budesonide) in vitro. The expression of intercellular adhesion
      molecule 1 (ICAM-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1)
      was examined using qPCR and ELISA, respectively. Moreover, the additive effects
      of azelastine and budesonide nasal spray on nasal ICAM-1 level and total nasal
      symptom scores were evaluated in six uncontrolled severe AR patients by
      budesonide nasal spray alone. We found azelastine significantly inhibited
      cytokine-induced ICAM-1 upregulation, which is reversed by MKP-1 silencing.
      Azelastine and budesonide additively increased MKP-1 expression and inhibited
      ICAM-1 expression in vitro. After treatment for two consecutive weeks, combined
      azelastine and budesonide nasal spray significantly decreased nasal ICAM-1 level
      and TNSS in six uncontrolled AR patients. Our findings suggested that azelastine
      is able to additively enhance the anti-inflammatory effect of budesonide by
      modulating MKP-1 expression, which may implicate in the treatment of uncontrolled
      severe AR. 

PMID- 25060978
TI  - On the need for comprehensive assessment of impact of comorbidity in elderly
      patients with head and neck cancer.

PMID- 25060979
TI  - Outcomes of patients with lobular in situ neoplasia of the breast: the role of
      vacuum-assisted biopsy.
AB  - OBJECTIVES: To audit the outcomes of patients with non-pleomorphic lobular in
      situ neoplasia (LISN) of the breast and clarify the role of vacuum-assisted
      biopsy (VAB), surgical biopsy and conservative management for this condition.
      MATERIALS AND METHOD: A single-centre retrospective review of hospital databases
      covering a 14-year period was performed. Patients with LISN as the most pertinent
      diagnosis on core needle biopsy (CNB), vacuum-assisted biopsy (VABs) or surgical
      biopsy were identified. The radiological features, histopathological findings and
      outcome of subsequent annual mammography were recorded. RESULTS: Between 1998 and
      2012 there were 70 patients with LISN as the most pertinent diagnosis at CNB, VAB
      or surgery. 52 underwent VAB, typically 18 11-gauge samples. The pathology was
      upgraded from the preceding 14-gauge CNB in 7 cases. Of 11 patients who underwent
      surgery after VAB, one (who had undergone a low tissue yield VAB) was upgraded.
      There were no new breast cancers during a mean annual mammographic follow-up
      period of 53 months in 40 patients who had VAB with complete radiological
      histopathological concordance. CONCLUSION: Provided there is adequate tissue
      sampling and radiological-pathological concordance, VAB is a safe alternative to
      open biopsy in the management of non-pleomorphic LISN.

PMID- 25060980
TI  - Macitentan: a review of its use in patients with pulmonary arterial hypertension.
AB  - Macitentan (Opsumit((r))) is an orally active, dual endothelin receptor
      antagonist (ERA) with tissue targeting properties. Macitentan was approved
      recently in the EU (as monotherapy or combination therapy) for the long-term
      treatment of pulmonary arterial hypertension (PAH) in adults of WHO functional
      class II or III, and in the USA for the treatment of PAH (WHO group I) to delay
      disease progression and reduce hospitalization for PAH. This article reviews the
      pharmacological properties, efficacy and tolerability data relevant to the use of
      macitentan in this indication. Treatment with macitentan 10 mg once daily
      significantly reduced the risk for the primary composite endpoint of morbidity
      and mortality in patients with PAH (mostly WHO functional class II or III) in the
      large, randomized, placebo-controlled SERAPHIN study. Other efficacy outcomes,
      including exercise capacity, haemodynamic parameters and health-related quality
      of life also improved significantly with macitentan relative to placebo.
      Macitentan was generally well tolerated in this study. As with other ERAs,
      haemoglobin levels decreased with macitentan therapy; however, these were not
      progressive and stabilized following longer-term treatment. Although comparative
      studies are needed to definitively position macitentan with respect to other
      approved agents, current evidence suggests that macitentan is a useful treatment
      option for initial therapy in patients with WHO functional class II or III PAH,
      which has the potential advantage of once-daily administration. 

PMID- 25060981
TI  - New therapies for hepatitis C: considerations in patients with renal impairment.
AB  - Hepatitis C virus (HCV) is a major public health issue because infection may lead
      to liver failure, cirrhosis and hepatocellular carcinoma. In patients with renal
      dysfunction, hepatitis C can also worsen the underlying renal disease. Treating
      HCV infection is thus mandatory in this population. New therapies for hepatitis C
      have recently been developed, and some have been launched. Most of them are used
      in combination with the current standard of care, ribavirin and pegylated
      interferon alfa. Some of them can be used in regimens without ribavirin and/or
      pegylated interferon. However, few data are available on dosage adjustment for
      renal function in patients receiving these very new drugs. We reviewed the
      literature on this subject and gathered information, although scarce, to propose
      guidelines for using these drugs in patients with chronic kidney disease.

PMID- 25060982
TI  - OnabotulinumtoxinA (Botox((r))): a review of its use in the treatment of urinary
      incontinence in patients with multiple sclerosis or subcervical spinal cord
      injury.
AB  - OnabotulinumtoxinA (BOTOX((r))) is a type A neurotoxin derived from Clostridium
      botulinum bacteria that is approved as treatment for urinary incontinence (UI) in
      patients with neurogenic detrusor overactivity resulting from multiple sclerosis
      (MS) or subcervical spinal cord injury (SCI) who are not adequately treated by
      antimuscarinics. This article reviews the pharmacology of intradetrusor
      onabotulinumtoxinA in this indication. The presumed mode of action of
      onabotulinumtoxinA in bladder disorders is by interfering with efferent
      innervation of the detrusor muscle and afferent pathways involved in the
      micturition reflex. In phase III trials in adult patients with MS or SCI with UI
      who were not adequately treated with antimuscarinics, intradetrusor
      onabotulinumtoxinA 200 U produced significantly greater mean changes (reductions)
      from baseline in UI episodes/week at week 6 than placebo (primary endpoint).
      Similar significant benefits of intradetrusor onabotulinumtoxinA 200 U over
      placebo were observed on other UI, urodynamic, health-related quality of life and
      treatment satisfaction endpoints. Intradetrusor onabotulinumtoxinA 200 U was
      generally well tolerated, with the most frequent adverse events being urinary
      tract infections and urinary retention. Few patients discontinued treatment
      because of adverse events. Based on interim analyses of an extension study of the
      phase III trials, repeat injections of onabotulinumtoxinA 200 U were similarly
      efficacious and well tolerated. Intradetrusor onabotulinumtoxinA represents a
      clinically important advance in the therapy of UI in patients with MS or SCI who
      have not responded to antimuscarinics or who are unable to tolerate
      antimuscarinics. 

PMID- 25060983
TI  - Custom-designed arrays of anodic alumina nanochannels with individually tunable
      pore sizes.
AB  - We demonstrate a process to selectively tune the pore size of an individual
      nanochannel in an array of high-aspect-ratio anodic aluminum oxide (AAO)
      nanochannels in which the pore sizes were originally uniform. This novel process
      enables us to fabricate arrays of AAO nanochannels of variable sizes arranged in
      any custom-designed geometry. The process is based on our ability to selectively
      close an individual nanochannel in an array by using focused ion beam (FIB)
      sputtering, which leads to redeposition of the sputtered material and closure of
      the nanochannel with a capping layer of a thickness depending on the energy of
      the FIB. When such a partially capped array is etched in acid, the capping layers
      are dissolved after different time delays due to their different thicknesses,
      which results in differences in the time required for the following pore-widening
      etching processes and therefore creates an array of nanochannels with variable
      pore sizes. The ability to fabricate such AAO templates with high-aspect-ratio
      nanochannels of tunable sizes arranged in a custom-designed geometry paves the
      way for the creation of nanophotonic and nanoelectronic devices. 

PMID- 25060984
TI  - Question the questions on CPAF.

PMID- 25060985
TI  - Prospective assessment of trocar-specific morbidity in laparoscopy.
AB  - BACKGROUND: The purpose of the present study was to challenge the hypothetical
      advantage of single port laparoscopy (SPL) over conventional laparoscopy by
      measuring prospectively the morbidity specifically related to conventional trocar
      sites (TS). METHODS: From November 2010 to December 2011, 300 patients undergoing
      various laparoscopic procedures were enrolled. Patient, surgery, and trocar
      characteristics were recorded. We evaluated at three time points (in-hospital and
      at 1 and 6 months postoperatively) specifically for each TS, pain (Visual Analog
      Scale), morbidity (infection, hematoma, hernia), and cosmesis (Patient Scar
      Assessment Score; PSAS). Patients designated their "worst TS," and a composite
      endpoint "bad TS" was defined to include any adverse outcome at a TS. RESULTS: We
      analyzed 1,074 TS. Follow-up was >90 %. Pain scores of >3/10 at 1 and 6 months
      postoperatively, were reported by 3 and 1 % of patients at the 5 mm TS and by 9
      and 1 % at the larger TS, respectively (5 mm TS vs larger TS; p = 0.001). Pain
      was significantly lower for TS located in the lower abdomen than for the upper
      abdomen or the umbilicus (p = 0.001). The overall complication rate was <1 % and
      significantly lower for the 5 mm TS (hematoma p = 0.046; infection p = 0.0001).
      No hernia was found. The overall PSAS score was low and significantly lower for
      the 5 mm TS (p = 0.0001). Significant predictors of "bad TS" were larger TS (p =
      0.001), umbilical position (p = 0.0001), emergency surgery (p = 0.0001),
      accidental trocar exit (p = 0.022), fascia closure (p = 0.006), and specimen
      extraction site (p = 0.0001). CONCLUSIONS: Specific trocar morbidity is low and
      almost negligible for 5 mm trocars. The umbilicus appears to be an unfavorable
      TS.

PMID- 25060986
TI  - Preliminary report of major surgery in liver transplant recipients receiving m
      TOR inhibitors without therapeutic discontinuation.
AB  - INTRODUCTION: Mammalian target rapamycin inhibitors (m-TORi) are increasingly
      used in patients undergoing liver transplantation (LT). Yet, there is rising
      concern that they also could impair wound healing and favor the development of
      several surgical complications. This report was designed to evaluate both
      feasibility and safety of major surgery in liver transplant recipients receiving
      m-TORi-based immunosuppression without therapeutic discontinuation. METHODS: From
      2007 to 2012, six liver transplant recipients underwent nine major abdominal or
      thoracic surgical procedures without m-TORi discontinuation or specific dosage
      adjustment. Their characteristics and postoperative outcomes were retrospectively
      analyzed. RESULTS: Indications for m-TORi were de novo or recurrent malignant
      disease in five patients and calcineurin inhibitors related neurologic toxicity
      in one patient. Abdominal procedures, thoracic procedures, and combined thoracic
      and abdominal procedures were performed in six, two, and one cases respectively.
      Emergency surgery was performed in one case and elective procedures were
      performed in eight cases, including five for malignant disease and three for late
      surgical complications following LT. No patient died postoperatively. One major
      complication was observed, but no patient required reoperation. No evisceration,
      incisional surgical site infection, or lymphocele occurred. CONCLUSIONS: Major
      surgery in liver transplant recipients receiving m-TOR inhibitors appears both
      feasible and safe without therapeutic discontinuation or specific dosage
      adjustment.

PMID- 25060987
TI  - During early and mid-adolescence, greater mental toughness is related to
      increased sleep quality and quality of life.
AB  - The aim of this study was to explore the association between mental toughness,
      subjective sleep, physical activity, and quality of life during early and mid
      adolescence. A total of 1475 participants (mean age = 13.4 years; range: 11-16
      years) took part in the study. They completed questionnaires related to mental
      toughness, physical activity, subjective sleep, and quality of life. Greater
      mental toughness was related to more favorable quality of life and increased
      subjective sleep. Mental toughness was not related to physical activity.
      Increased mental toughness, favorable quality of life, and sleep are related
      during early and mid-adolescence. Against our expectations, mental toughness was
      not related to physical activity.

PMID- 25060988
TI  - Understanding causal associations between self-rated health and personal
      relationships in older adults: A review of evidence from longitudinal studies.
AB  - BACKGROUND: As we age we experience many life changes in our health, personal
      relationships, work, or home life which can impact on other aspects of our life.
      There is compelling evidence that how we feel about our health influences, or is
      influenced by, the personal relationships we experience with friends and
      relatives. Currently the direction this association takes is unclear. AIM: To
      assess the level of published evidence available on causal links between self
      rated health and personal relationships in older adults. METHODS: MEDLINE,
      CINAHL, and PsycINFO searches from inception to June 2012 and hand searches of
      publication lists, reference lists and citations were used to identify primary
      studies utilizing longitudinal data to investigate self-rated health and personal
      relationships in older adults. RESULTS: Thirty-one articles were identified. Only
      three articles employed methods suitable to explore causal associations between
      changes in self-rated health and changes in personal relationships. Two of these
      articles suggested that widowhood leads to a reduction in self-rated health in
      the short term, while the remaining article suggested a causal relationship
      between self-rated health and negative emotional support from family or friends,
      but this was complex and mediated by self-esteem and sense of control.
      CONCLUSION: While there is an abundance of longitudinal aging cohorts available
      which can be used to investigate self-rated health and personal relationships
      over time the potential for these databases to be used to investigate causal
      associations is currently not being recognized.

PMID- 25060989
TI  - Altered spontaneous neuronal activity of visual cortex and medial anterior
      cingulate cortex in treatment-naive posttraumatic stress disorder.
AB  - BACKGROUND: Although no more traumatic stimuli exists, a variety of symptoms are
      persisting in chronic Posttraumatic Stress Disorder (PTSD) patients. It is
      therefore necessary to explore the spontaneous brain activity of treatment-naive
      PTSD patients during resting-state. METHOD: Seventeen treatment-naive PTSD
      patients and twenty traumatized controls were recruited and underwent a resting
      functional magnetic resonance imaging (Rs-fMRI) scan. The differences of regional
      brain spontaneous activity between the participants with and without PTSD were
      measured by Amplitude of Low-frequency fluctuation (ALFF). The relationship
      between the altered brain measurements and the symptoms of PTSD were analyzed.
      RESULT: Compared to traumatized controls, the PTSD group showed significantly
      altered ALFF in many emotion-related brain regions, such as the medial anterior
      cingulate cortex (MACC), dorsolateral prefrontal cortex (DLPFC), insular (IC),
      middle temporal gyrus (MTG), and ventral posterior cingulate cortex (VPCC).
      Interestingly this is the first report of a hyperactive visual cortex (V1/V2)
      during resting-state in treatment-naive PTSD patients. There were significant
      positive correlations between ALFF values in the bilateral visual cortex and re
      experiencing or avoidance in PTSD. Negative correlation was observed between ALFF
      values in MACC and avoidance. CONCLUSION: This study suggested that the visual
      cortex and the MACC may be involved in the characteristic symptoms of chronic
      PTSD, such as re-experiencing and avoidance. Future studies that focus on these
      areas of the brain are required, as alteration of these areas may act as a
      biomarker and could be targeted in future treatments for PTSD.

PMID- 25060990
TI  - Prognostic value of histologic grading for feline mammary carcinoma: a
      retrospective survival analysis.
AB  - Feline mammary carcinoma is highly malignant and generally associated with a poor
      prognosis, although studies suggest the range of survival times in affected cats
      is broad. Histologic grading of these tumors is achieved using the Elston and
      Ellis system, originally developed for human breast cancer. In cats, however,
      classification using this method has variable prognostic value. Therefore,
      objectives of this study were (1) to evaluate the Elston and Ellis grading system
      for feline mammary carcinoma in a predominantly spayed population and (2) to
      determine whether modification of this system or development of a novel system
      improved the prognostic value of histologic grading. Survey data and histologic
      features for 108 carcinomas from 97 cats were analyzed with respect to overall
      survival. Elston and Ellis grading failed to correlate significantly with overall
      survival. Using multivariable analysis, lymphovascular invasion, nuclear form,
      and mitotic count each demonstrated independent prognostic significance (P =
      .008, <.001, and .004, respectively). Modifications of the Elston and Ellis
      system and a novel grading system were proposed based on these results; all
      showed significant correlation with overall survival (P < .001). Median survival
      times were 27, 29, or 31 months for grade I; 14, 12, or 14 months for grade II;
      and 13, 5, or 8 months for grade III carcinomas using the mitotic-modified Elston
      and Ellis, the revised Elston and Ellis, or the novel grading system,
      respectively. Based on this retrospective study, adoption of the species-specific
      systems as proposed here may improve the prognostic value of histologic grading
      for feline mammary carcinoma. 

PMID- 25060991
TI  - Targeting survival and cell trafficking in multiple myeloma and Waldenstrom
      macroglobulinemia using pan-class I PI3K inhibitor, buparlisib.
AB  - The phosphatidylinositol-3 kinase (PI3K) pathway is activated in multiple myeloma
      (MM) and Waldenstrom Macroglobulenima (WM), and plays a crucial role in tumor
      progression and drug resistance. In this study, we characterized the role of pan
      class I PI3K inhibition on cell trafficking and survival of MM and WM cells. We
      tested the effect of pan-class I PI3K inhibition by siRNA silencing or
      pharmacologic inhibition with buparlisib on MM cell survival, apoptosis and cell
      cycle in vitro and tumor growth and mobilization of MM cells in vivo. We then
      evaluated buparlisib-dependent mechanisms of induced MM cell mobilization.
      Moreover, the effect of buparlisib on cell survival, apoptosis, and adhesion of
      WM cells to bone marrow stromal cells (BMSCs) has been evaluated. We showed that
      buparlisib induced toxicity in MM cells, supported by induction of apoptosis and
      cell cycle arrest. Buparlisib was also found to reduce tumor progression in vivo.
      Importantly, buparlisib enhanced MM cell mobilization in vivo which was driven by
      decreased adhesion of MM cells to BMSCs and increased chemotaxis via up
      regulation of CXCR4 expression. Similar to its effects on MM cells, buparlisib
      also induced cell survival and apoptosis, and decreased adhesion in WM cells.
      These data highlight the critical contribution of class I PI3K signaling to the
      regulation of survival and cell dissemination in B-cell malignancies.

PMID- 25060992
TI  - Cellular metabolic, stress, and histological response on exposure to acute
      toxicity of endosulfan in tilapia (Oreochromis mossambicus).
AB  - Endosulfan is one of the most hazardous organochlorines pesticides responsible
      for environmental pollution, as it is very persistent and shows bio
      magnification. This study evaluated the impact of acute endosulfan toxicity on
      metabolic enzymes, lysozyme activities, heat shock protein (Hsp) 70 expression,
      and histopathology in Tilapia (Oreochromis mossambicus). Among the indicators
      that were induced in dose dependent manner were the enzymes of amino acid
      metabolism (serum alanine aminotransferase and aspartate aminotransferase),
      carbohydrate metabolism (serum lactate dehydrogenase), pentose phosphate pathway
      (Glucose-6-phosphate dehydrogenase) as well as lysozyme and Hsp70 in liver and
      gill, while liver and gill Isocitrate dehydrogenase (TCA cycle enzyme) and marker
      of general energetics (Total adenosine triphosphatase) were inhibited.
      Histopathological alterations in gill were clubbing of secondary gill lamellae,
      marked hyperplasia, complete loss of secondary lamellae and atrophy of primary
      gill filaments. Whereas in liver, swollen hepatocyte, and degeneration with loss
      of cellular boundaries were distinctly noticed. Overall results clearly
      demonstrated the unbalanced metabolism and damage of the vital organs like liver
      and gill in Tilapia due to acute endosulfan exposure.

PMID- 25060993
TI  - Atypical course in individuals from Spanish families with benign familial
      infantile seizures and mutations in the PRRT2 gene.
AB  - A benign prognosis has been claimed in benign familial infantile seizures (BFIS).
      However, few studies have assessed the long-term evolution of these patients. The
      objective of this study is to describe atypical courses and presentations in BFIS
      families with mutations in PRRT2 gene. We studied clinically affected individuals
      from five BFIS Spanish families. We found mutations in PRRT2 in all 5 families. A
      non-BFIS phenotype or an atypical BFIS course was found in 9/25 (36%) patients
      harbouring a PRRT2 mutation. Atypical features included neonatal onset, mild
      hemiparesis, learning difficulties or mental retardation, and recurrent seizures
      during adulthood. We also report a novel PRRT2 mutation (c.121_122delGT). In BFIS
      families an atypical phenotype was present in a high percentage of the patients.
      These findings expand the clinical spectrum of PRRT2 mutations including non
      benign epileptic phenotypes. 

PMID- 25060994
TI  - Early evaluation of the therapeutic effectiveness in children with epilepsy by
      quantitative EEG: a model of Mozart K.448 listening--a preliminary study.
AB  - PURPOSE: There are many treatments being developed for patients with epilepsy,
      including anti-epileptic drugs, ketogenic diet and vagus nerve stimulation. To
      date, there is a lack of valid methods to predict at an early stage the
      therapeutic effects on patients with epilepsy who receive one of these
      treatments. Our previous studies revealed that epileptiform discharges which were
      observed in patients with epilepsy were significantly decreased while listening
      to Mozart K.448. In this study, we attempted to develop a useful marker by
      utilizing a quantitative electroencephalogram (qEEG) method in analyzing the
      features of EEG to early evaluate the effect of the music on children with
      epilepsy, even without epileptiform discharges. METHODS: EEG segments from 19
      Taiwanese children who were selected from a large screen study of music effect
      (eight boys and 11 girls) diagnosed with epilepsy were analyzed. EEG examinations
      were performed in two parallel periods in each patient; before, and while
      listening to Mozart K.448's first movement (8 min 22s) and EEG data were compared
      by qEEG. EEG segments were classified into music effective/ineffective group. The
      term "effective" was defined as patient exposure to music resulting in over a 25%
      reduction in epileptiform discharges. On the contrary, the term "ineffective" was
      defined as patient exposure to music resulting in less than a 5% reduction in
      epileptiform discharges. RESULTS: There were four global feature descriptors
      selected for the music effective/ineffective classification. Two descriptors,
      DecorrTime_avg_AVG and DecorrTime_std_AVG, were related to the EEG feature
      "decorrelation" whereas the other two descriptors, RelPowGamma_avg_SNR and
      RelPowGamma_std_SNR, were related to "relative power of gamma." There were
      significantly higher RelPowGamma_std_SNR (0.190+/-0.133 vs. -0.026+/-0.119,
      p=0.0029), DecorrTime_std_AVG (0.005+/-0.004 vs. 0.0003+/-0.0016, p=0.0055),
      DecorrTime_avg_AVG (0.005+/-0.005 vs. -0.002+/-0.008, p=0.0179), and
      RelPowGamma_avg_SNR (0.176+/-0.219 vs. -0.078+/-0.244, p=0.0222) in the effective
      group than in the ineffective group. The precision rate of classification was
      0.953. CONCLUSIONS: Using qEEG, we have developed a useful model for predicting
      therapeutic effectiveness of music in patients with epilepsy. Among the limited
      number of patients, the tool is of potential to predict the effectiveness in
      patients even without epileptiform discharges. It is worthwhile in the
      application of other therapeutic model.

PMID- 25060995
TI  - Self-rated and assessed cognitive functions in epilepsy: impact on quality of
      life.
AB  - AIM OF THE STUDY: To compare the effects of perceived and assessed cognitive
      functions on quality of life (QoL) in patients with epilepsy (PWE). METHODS: The
      study analyzed the data from a series of PWE who compiled the Quality of Life in
      Epilepsy-89 Inventory (QOLIE-89) and the Multiple Ability Self-Report
      Questionnaire (MASQ) for QoL and perceived cognitive abilities, respectively. The
      State-Trait Anxiety and Beck Depression inventories were used to assess mood.
      Neuropsychological tests evaluated abstract reasoning, attention, conceptual
      motor tracking, constructional praxis, language, verbal and non-verbal memory,
      abstraction, category shifting, verbal fluency, and visual-spatial abilities.
      RESULTS: The QOLIE-89 overall score was predicted by the Mood and Attention and
      Executive Functions factors and MASQ scores, explaining 38, 6, and 4% of its
      variance, while disease duration, seizure frequency, and schooling determined
      16%. The QOLIE-89 Psychosocial, Cognitive, and Physical Performance sub-domains
      related to mood. The Cognitive and Physical Performance factors also related to
      the MASQ and Attention and Executive Functions factor scores, respectively.
      CONCLUSIONS: In PWE, self-rated and assessed cognitive deficits may influence
      QoL, explaining 10% of its variance irrespective from mood and clinical
      variables. Treating cognitive deficits and their perception may help improve QoL.

PMID- 25060996
TI  - Low vitamin D levels are common in patients with epilepsy.
AB  - PURPOSE: Vitamin D is important for bone health, and vitamin D deficiency may
      contribute to other disorders (e.g., autoimmune, infections, cancer,
      degenerative, diabetic, and vascular). Enzyme-inducing antiepileptic drugs have
      been particularly implicated for osteoporosis risk given their effects on vitamin
      D. We examined the prevalence of vitamin D deficiency in adult epilepsy patients.
      METHODS: We conducted an observational study of consecutive epilepsy patients
      treated by two clinicians at the Emory University Epilepsy Center from 2008 to
      2011 in order to determine the frequency of low vitamin D levels and possible
      differential antiepileptic drug risks. Vitamin D 25-OH levels were categorized as
      low (<20 ng/ml), borderline (20-29 ng/ml), or normal (>=30 ng/ml). Antiepileptic
      drugs were categorized based on their enzyme inducing properties. Descriptive and
      inferential statistics were employed. RESULTS: Vitamin D levels were obtained on
      596 patients with epilepsy. Mean age was 41 years (SD=14; range=18-81); 56% were
      women. Race/ethnicity was 55% Caucasian, 34% Black, 2% Asian, and 7% Unknown. The
      mean vitamin D level was 22.5 (SD=11.9; range = <4 to 98), and 45% had level <20
      ng/ml. Mean vitamin D levels (F=6.48, p=.002) and frequencies of vitamin D
      categories (p=.002, Chi square test) differed across the antiepileptic drug
      groups. Vitamin D deficiency was present in 54% of enzyme-inducing and 37% of non
      enzyme-inducing antiepileptic drugs groups. CONCLUSIONS: Vitamin D deficiency is
      common in patients with epilepsy on antiepileptic drugs. Monitoring of vitamin D
      should be considered as part of the routine management of patients with epilepsy.

PMID- 25060997
TI  - Two-year follow-up with eslicarbazepine acetate: a consecutive, retrospective,
      observational study.
AB  - PURPOSE: Eslicarbazepine acetate (ESL) is a new generation voltage-gated sodium
      channel blocker. It has completed one phase II clinical trial and three phase III
      clinical trials, two of which with 1-year open label extensions. ESL was approved
      in 2009 by the European Medicines Agency as adjunctive therapy in adults with
      partial-onset seizures with or without secondary generalization. It is marketed
      in Portugal since April 1st 2010. Despite good safety and efficacy shown in
      clinical trials, little is known about its effectiveness in a clinical day-to-day
      setting. Our purpose was to assess the post-marketing experience with ESL in our
      centre, in terms of safety and efficacy profile, and ascertain whether the
      results were comparable to the published data. METHODS: This is a retrospective,
      consecutive, single-centre 2-year observational study. All the patients who
      initiated treatment with ESL between April 1st 2010 and October 31st 2011 at
      Hospital de Santo Antonio were consecutively included. Data was collected on
      demographics, clinical features, adverse events and treatment response, using a
      standardized data form. Follow-up data was considered until October 31st 2013.
      Efficacy analysis was performed using an "intention to treat" approach. KEY
      FINDINGS: We included 152 patients, 74 (48.7%) female. Mean age was 38.5 years
      old (sd=14.2). Eight patients were less than 18 years old. Mean epilepsy duration
      was 26.8 (sd=13.1) years and mean seizure frequency in the previous 3 months was
      19.7 seizures per month. At baseline, about 57.9% of all patients were taking <=2
      concomitant AEDs. The total adverse rate was 42.1% (64/152), with 50.0% (32/64)
      leading to treatment discontinuation. The most frequent adverse events were
      dizziness and somnolence/slowness. Adverse events were higher in regimens
      including carbamazepine, and mean age was higher in the patients reporting
      adverse events. Retention rates as estimated by Kaplan-Meyer curves were 82.9%,
      71.3%, 65.1% and 62.8%, respectively, at 6, 12, 18 and 24 months. Retention time
      was not influenced by gender, diagnosis, age or epilepsy duration. Fifty-six
      patients (36.8%) dropped out of treatment, 32 (57.1%) due to adverse events, 19
      (33.9%) due to lack of efficacy and 5 (8.9%) for other reasons. At 6,12,18 and 24
      months, the responder rates were 25.7%, 25.7%, 19.0% and 17.1%, respectively and
      favourable global clinical impression rates were 27.7%, 19.7%, 17.8% and 16.5%.
      SIGNIFICANCE: This is the first study reporting follow-up data for up to 2 years
      in patients treated with ESL in the setting of daily clinical practice. The
      retention rates in our study are sustained throughout the 2 years of follow-up,
      and at 6 and 12 months are globally comparable to those of phase III trials and
      open-label extensions. The adverse event rate is also comparable to previous
      studies, and no new safety issues attributable to ESL were found. Responder rates
      were lower than those of previous studies, even though efficacy results must be
      interpreted with caution given the different study design. Thus, ESL appears to
      be a clinically useful add-on AED, with good safety profile and high retention
      rates, even in a very refractory group of patients like the presented cohort.

PMID- 25060998
TI  - Basis set error estimation for DFT calculations of electronic g-tensors for
      transition metal complexes.
AB  - We present a detailed study of the basis set dependence of electronic g-tensors
      for transition metal complexes calculated using Kohn-Sham density functional
      theory. Focus is on the use of locally dense basis set schemes where the metal is
      treated using either the same or a more flexible basis set than used for the
      ligand sphere. The performance of all basis set schemes is compared to the
      extrapolated complete basis set limit results. Furthermore, we test the
      performance of the aug-cc-pVTZ-J basis set developed for calculations of NMR spin
      spin and electron paramagnetic resonance hyperfine coupling constants. Our
      results show that reasonable results can be obtain when using small basis sets
      for the ligand sphere, and very accurate results are obtained when an aug-cc-pVTZ
      basis set or similar is used for all atoms in the complex.

PMID- 25061002
TI  - Phage tail-like particles kill Clostridium difficile and represent an alternative
      to conventional antibiotics.
AB  - BACKGROUND: Current Clostridium difficile infection (CDI) antibiotic regimens
      have become increasingly ineffective at achieving cure and preventing recurrence.
      A recently developed alternative to conventional antibiotics are phage tail-like
      particles (PTLPs), which are proteins that are morphologically similar to
      bacteriophages and are produced by C difficile. This study examines the in vitro
      killing spectrum of a previously unreported PTLP isolated from a clinical isolate
      of C difficile. METHODS: Using patient-derived samples from an institutional
      review board-approved C difficile tissue bank, a ribotype 078 C difficile isolate
      was anaerobically incubated on blood agar plates that were preswabbed with
      norfloxacin to induce the production of PTLPs. Concentrated PTLP populations were
      confirmed using transmission electron microscopy. Using a standard lawn spot
      approach, bactericidal activity was assessed as indicated by a clearing within
      the bacterial lawn. The PTLP genomic cluster was also fully sequenced and open
      reading frames were annotated according to predicted function. RESULTS: PTLPs
      were assessed using 64 patient-derived C difficile isolates of varying ribotypes.
      PTLPs demonstrated complete bactericidal activity in 21 of 25 ribotype 027
      isolates with partial activity in 2 of the 25. Complete bactericidal activity was
      not demonstrated against any other ribotype or non-difficile bacteria, suggesting
      a species and ribotype specificity. Functional genes, which may be necessary for
      killing, were identified within the PTLP genetic locus. CONCLUSION: PTLPs
      demonstrate capability in eradicating C difficile in vitro, and with further
      development, may represent an organism-specific, microbiome-sparing therapy for
      CDI.

PMID- 25061004
TI  - Pd-Ni alloy nanoparticle doped mesoporous SiO2 film: the sacrificial role of Ni
      to resist Pd-oxidation in the C-C coupling reaction.
AB  - A Pd-Ni alloy nanoparticle (NP) doped mesoporous SiO2 film was synthesized using
      a one pot inorganic-organic sol-gel process in the presence of structure director
      P123. Pure Pd and Ni NP containing films were also synthesized as controls.
      Overall a composition of 10 mol% metal (in the case of Pd-Ni, 5 mol% of each
      metal) and 90 equivalent mol% SiO2 was maintained in the heat-treated films.
      Grazing incidence X-ray diffraction and transmission electron microscopy studies
      of the final heat-treated Pd-Ni doped films revealed the (111) oriented growth of
      the Pd-Ni alloy NPs, with an average size of 5.3 nm, residing inside the
      mesopores of the SiO2 film. We performed the C-C coupling reaction employing the
      film-catalysts and the progress of the reaction was monitored using a
      fluorimeter. Overall, only the Pd-Ni alloy NP doped film showed good catalytic
      activity with excellent recyclability. It has been determined that the higher
      oxidising ability of metallic Ni restricted the oxidation of Pd in the Pd-Ni
      alloy catalyst under the reaction conditions, leading to the maintained
      reusability in consecutive cycles. 

PMID- 25061003
TI  - Definition of a standard lymphadenectomy in surgery for pancreatic ductal
      adenocarcinoma: a consensus statement by the International Study Group on
      Pancreatic Surgery (ISGPS).
AB  - BACKGROUND: The lymph node (Ln) status of patients with resectable pancreatic
      ductal adenocarcinoma is an important predictor of survival. The survival benefit
      of extended lymphadenectomy during pancreatectomy is, however, disputed, and
      there is no true definition of the optimal extent of the lymphadenectomy. The aim
      of this study was to formulate a definition for standard lymphadenectomy during
      pancreatectomy. METHODS: During a consensus meeting of the International Study
      Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement
      based on available literature and their experience. RESULTS: The nomenclature of
      the Japanese Pancreas Society was accepted by all participants. Extended
      lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the
      left side of the superior mesenteric artery (SMA) and around the celiac trunk,
      splenic artery, or left gastric artery showed no survival benefit compared with a
      standard lymphadenectomy. No level I evidence was available on prognostic impact
      of positive para-aortic Ln's. Consensus was reached on selectively removing
      suspected Ln's outside the resection area for frozen section. No consensus was
      reached on continuing or terminating resection in cases where these nodes were
      positive. CONCLUSION: Extended lymphadenectomy cannot be recommended. Standard
      lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no.
      5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the
      body and tail of the pancreas, removal of stations 10, 11, and 18 is standard.
      Furthermore, lymphadenectomy is important for adequate nodal staging. Both
      pancreatic resection in relatively fit patients or nonresectional palliative
      treatment were accepted as acceptable treatment in cases of positive Ln's outside
      the resection plane. This consensus statement could serve as a guide for surgeons
      and researchers in future directives and new clinical studies.

PMID- 25061005
TI  - A longitudinal study of the effect of psychosocial factors on exclusive
      breastfeeding duration.
AB  - OBJECTIVE: to examine the effect of psychosocial factors on exclusive
      breastfeeding duration to six months postpartum DESIGN: longitudinal, prospective
      questionnaire based study. SETTING: participants were recruited from a publically
      funded antenatal clinic located in the western metropolitan region of Melbourne,
      Victoria, Australia and asked to complete questionnaires at three time points; 32
      weeks pregnancy, two months postpartum and six months postpartum. PARTICIPANTS:
      the participants were 125 pregnant women aged 22-44 years. MEASUREMENTS AND
      FINDINGS: psychosocial variables such as breastfeeding self-efficacy, body
      attitude, psychological adjustment, attitude towards pregnancy, intention,
      confidence and motivation to exclusively breastfeed and importance of exclusive
      breastfeeding were assessed using a range of psychometrically validated tools.
      Exclusive breastfeeding behaviour up to six months postpartum was also measured.
      At 32 weeks gestation a woman's confidence to achieve exclusive breastfeeding was
      a direct predictor of exclusive breastfeeding duration to six months postpartum.
      At two months postpartum, psychological adjustment and breastfeeding self
      efficacy were predictive of exclusive breastfeeding duration. Finally, at six
      months postpartum, psychological adjustment, breastfeeding self-efficacy,
      confidence to maintain and feeling fat were directly predictive of exclusive
      breastfeeding duration. KEY CONCLUSIONS: psychosocial factors are significantly
      predictive of exclusive breastfeeding duration. Self-efficacy, psychological
      adjustment, body image, motivation and confidence are all important psychosocial
      factors implicated in a woman's ability to maintain exclusive breastfeeding over
      time. IMPLICATIONS FOR PRACTICE: Individualised antenatal breastfeeding education
      and support may be strengthened by strategies that build a woman's confidence to
      exclusive breastfeeding. Implementing psychosocial supports and methods providing
      positive feedback that increase a woman's self-efficacy to exclusively breastfeed
      to six months are also important two months postpartum.

PMID- 25061007
TI  - Molecular and serologic detection of Coxiella burnetii in native Korean goats
      (Capra hircus coreanae).
AB  - The occurrence of Q fever in native Korean goats (Capra hircus coreanae) was
      investigated for the first time in the country using ELISA and PCR. A total of
      597 blood samples were collected from goats belonging to five different provinces
      of Korea. To detect Coxiella burnetii, sera were separated from the whole blood
      and analysed by ELISA; DNA was extracted directly from the whole blood and
      analysed by PCR. Overall, 114 (19.1%, 95% C.I.=16.1-22.4) and 57 goats (9.5%, 95%
      C.I.=7.5-12.2) tested positive for C. burnetii in the ELISA- and PCR-based
      screening, respectively, while 18 goats (3.0%, 95% C.I.=1.9-4.7) tested positive
      in both the assays. There was a significant difference between the number of
      ELISA- and PCR-positive goats (P<0.05). The seroprevalence of Q fever was
      significantly higher among the adult goats (>=1y, 22.0%) than among the young
      goats (<1y, 13.8%) (P<0.05). While the results of the serologic analysis showed
      no seasonal variation, data from the PCR-based assay indicated that there were a
      higher number of positive cases during the cold seasons. Because Q fever
      infection has high rates of prevalence in native Korean goats, further studies on
      humans at a high risk of contracting this disease should be conducted. The PCR
      based assay used in this study is a useful method for the direct detection of C.
      burnetii in blood samples from small ruminants. 

PMID- 25061006
TI  - The development of a new breast feeding assessment tool and the relationship with
      breast feeding self-efficacy.
AB  - OBJECTIVE: to develop a breast feeding assessment tool to facilitate improved
      targeting of optimum positioning and attachment advice and to describe the
      changes seen following the release of a tongue-tie. DESIGN: development and
      validation of the Bristol Breastfeeding Assessment Tool (BBAT) and correlation
      with breast feeding self-efficacy. SETTING: maternity hospital in South West
      England. PARTICIPANTS: 218 breast feeds (160 mother-infant dyads); seven midwife
      assessors. FINDINGS: the tool has more explanation than other tools to remind
      those supporting breast-feeding women about the components of an efficient breast
      feed. There was good internal reliability for the final 4-item BBAT (Cronbach's
      alpha=0.668) and the midwives who used it showed a high correlation in the
      consistency of its use (ICC=0.782). Midwives were able to score a breast feed
      consistently using the BBAT and felt that it helped them with advice to mothers
      about improving positioning and attachment to make breast feeding less painful,
      particularly with a tongue-tied infant. The tool showed strong correlation with
      breast feeding self-efficacy, indicating that more efficient breast feeding
      technique is associated with increased confidence in breast feeding an infant.
      CONCLUSIONS: the BBAT is a concise breast feeding assessment tool facilitating
      accurate, rapid breast feeding appraisal, and targeting breast feeding advice to
      mothers acquiring early breast feeding skills or for those experiencing problems
      with an older infant. Accurate assessment is essential to ensure enhanced breast
      feeding efficiency and increased maternal self-confidence. IMPLICATIONS FOR
      PRACTICE: the BBAT could be used both clinically and in research to target advice
      to improve breast feeding efficacy. Further research is needed to establish its
      wider usefulness.

PMID- 25061008
TI  - Dietary supplementation of Gracilariopsis persica is associated with some quality
      related sera and egg yolk parameters in laying quails.
AB  - BACKGROUND: Gracilariopsis persica (Gp) is one of the most abundant red algae
      distributed in the Persian Gulf, containing various bioactive components with
      hypolipedimic, hypoglycemic and antioxidant properties. Therefore using laying
      quails as a model we aimed to investigate the effect of dietary Gp on body
      weight, feed conversion, estradiol, progesterone, calcium and lipid levels in
      serum, as well as the high-density:low-density lipoprotein (HDL:LDL) ratio. Yolk
      cholesterol and yolk lipid oxidation were also evaluated. To accomplish this,
      diets containing 0, 10, 30 and 50 g kg(-1) Gp were fed to 5-week-old laying
      quails for 12 weeks. RESULTS: Our data revealed that Gp had no effect on body
      weight, feed conversion, triglycerides and estradiol levels of serum. Dietary Gp
      decreased the serum and yolk cholesterol in a dose-dependent manner. In addition,
      the sera progesterone and calcium levels and HDL:LDL ratios were increased by
      feeding diets containing 50 g kg(-1) Gp. Our results relating to yolk lipid
      oxidation showed that malondialdehyde content was decreased in Gp-fed laying
      quails. CONCLUSIONS: The results of the present study demonstrate that not only
      serum and egg yolk cholesterol levels, but also susceptibility of yolk lipids to
      oxidation, can be decreased by feeding Gp to laying quails.

PMID- 25061010
TI  - Update on putative novel antipsychotics.

PMID- 25061009
TI  - Lysosome: regulator of lipid degradation pathways.
AB  - Autophagy is a catabolic pathway that has a fundamental role in the adaptation to
      fasting and primarily relies on the activity of the endolysosomal system, to
      which the autophagosome targets substrates for degradation. Recent studies have
      revealed that the lysosomal-autophagic pathway plays an important part in the
      early steps of lipid degradation. In this review, we discuss the transcriptional
      mechanisms underlying co-regulation between lysosome, autophagy, and other steps
      of lipid catabolism, including the activity of nutrient-sensitive transcription
      factors (TFs) and of members of the nuclear receptor family. In addition, we
      discuss how the lysosome acts as a metabolic sensor and orchestrates the
      transcriptional response to fasting. 

PMID- 25061011
TI  - Highlights from the 2014 Schizophrenia International Research Society Conference
      April 5-9, 2014.
AB  - The 2014 Schizophrenia International Research Society (SIRS) Conference, held in
      Florence, Italy, attracted more than 1,700 attendees from over 55 countries to
      the stately Firenze Fiera Conference Center from April 5-9, 2014. Providing
      plenary sessions, special sessions, symposia, workshops, oral presentations and
      poster presentations, this 4th Biennial SIRS Conference was jointly sponsored by
      Vanderbilt University School of Medicine, Department of Psychiatry and SIRS. In
      conjunction with the Schizophrenia Research Forum, a Web project of the Brain and
      Behavior Research Foundation, and with our thanks to the SIRS organizers and
      staff, we bring you the following report on the meeting's discussions concerning
      drug therapy developments for schizophrenia. 

PMID- 25061012
TI  - A functional high-content miRNA screen identifies miR-30 family to boost
      recombinant protein production in CHO cells.
AB  - The steady improvement of mammalian cell factories for the production of
      biopharmaceuticals is a key challenge for the biotechnology community. Recently,
      small regulatory microRNAs (miRNAs) were identified as novel targets for
      optimizing Chinese hamster ovary (CHO) production cells as they do not add any
      translational burden to the cell while being capable of regulating entire
      physiological pathways. The aim of the present study was to elucidate miRNA
      function in a recombinant CHO-SEAP cell line by means of a genome-wide high
      content miRNA screen. This screen revealed that out of the 1, 139 miRNAs
      examined, 21% of the miRNAs enhanced cell-specific SEAP productivity mainly
      resulting in elevated volumetric yields, while cell proliferation was accelerated
      by 5% of the miRNAs. Conversely, cell death was diminished by 13% (apoptosis) or
      4% (necrosis) of all transfected miRNAs. Besides these large number of identified
      target miRNAs, the outcome of our studies suggest that the entire miR-30 family
      substantially improves bioprocess performance of CHO cells. Stable miR-30 over
      expressing cells outperformed parental cells by increasing SEAP productivity or
      maximum cell density of approximately twofold. Our results highlight the
      application of miRNAs as powerful tools for CHO cell engineering, identified the
      miR-30 family as a critical component of cell proliferation, and support the
      notion that miRNAs are powerful determinants of cell viability. 

PMID- 25061013
TI  - Synthesis and photocurrent of amorphous boron nanowires.
AB  - Although theoretically feasible, synthesis of boron nanostructures is challenging
      due to the highly reactive nature, high melting and boiling points of boron. We
      have developed a thermal vapor transfer approach to synthesizing amorphous boron
      nanowire using a solid boron source. The amorphous nature and chemical
      composition of boron nanowires were characterized by high resolution transmission
      electron microscopy, selected area electron diffraction, and electron energy loss
      spectroscopy. Optical properties and photoconduction of boron nanowires have not
      yet been reported. In our investigation, the amorphous boron nanowire showed much
      better optical and electrical properties than previously reported photo-response
      of crystalline boron nanobelts. When excited by a blue LED, the photo/dark
      current ratio (I/I0) is 1.5 and time constants in the order of tens of seconds.
      I/I0 is 1.17 using a green light.

PMID- 25061014
TI  - Kounis syndrome associated with brain injury after Hymenoptera sting: new
      presentation of an established entity.

PMID- 25061015
TI  - Pulmonary embolism and Takotsubo syndrome as comorbidities versus employing mere
      pulmonary embolism to model the Takotsubo syndrome pathophysiology.

PMID- 25061016
TI  - Virtual histology findings in rapid cardiac allograft vasculopathy progression
      and bioresorbable vascular scaffolds.

PMID- 25061018
TI  - Selective and efficient electrochemical biosensing of ultrathin molybdenum
      disulfide sheets.
AB  - Atomically thin molybdenum disulfide (MoS2) sheets were synthesized and isolated
      via solvent-assisted chemical exfoliation. The charge-dependent electrochemical
      activities of these MoS2 sheets were studied using positively charged hexamine
      ruthenium (III) chloride and negatively charged ferricyanide/ferrocyanide redox
      probes. Ultrathin MoS2 sheet-based electrodes were employed for the
      electrochemical detection of an important neurotransmitter, namely dopamine (DA),
      in the presence of ascorbic acid (AA). MoS2 electrodes were identified as being
      capable of distinguishing the coexistence of the DA and the AA with an excellent
      stability. Moreover, the enzymatic detection of the glucose was studied by
      immobilizing glucose oxidase on the MoS2. This study opens enzymatic and non
      enzymatic electrochemical biosensing applications of atomic MoS2 sheets, which
      will supplement their established electronic applications.

PMID- 25061017
TI  - Post-Traumatic Stress Symptoms in Post-ICU Family Members: Review and
      Methodological Challenges.
AB  - Family members of intensive care unit (ICU) patients are at risk for symptoms of
      post-traumatic stress disorder (PTSD) following ICU discharge. The aim of this
      systematic review is to examine the current literature regarding post-ICU family
      PTSD symptoms with an emphasis on methodological issues in conducting research on
      this challenging phenomenon. An extensive review of the literature was performed
      confining the search to English language studies reporting PTSD symptoms in adult
      family members of adult ICU patients. Ten studies were identified for review
      published from 2004 to 2012. Findings demonstrate a significant prevalence of
      family PTSD symptoms in the months following ICU hospitalization. However, there
      are several methodological challenges to the interpretation of existing studies
      and to the conduct of future research including differences in sampling,
      identification of risk factors and covariates of PTSD, and lack of consensus
      regarding the most appropriate PTSD symptom measurement tools and timing. 

PMID- 25061019
TI  - Occult bilateral invasive lobular carcinoma of the breast presenting as
      gastroduodenal metastases: a case report.
AB  - Breast cancer, after malignant melanoma, is the most common cancer metastasizing
      to the gastrointestinal tract [1,4]. Isolated gastrointestinal metastasis from
      breast cancer is a quite rare finding. We describe a female patient with a
      gastric metastasis from an undiagnosed breast cancer who presented to
      gastroenterology department with a symptoms of abdominal pain. 

PMID- 25061020
TI  - Malignant phyllodes tumor of the breast with liposarcomatous differentiation and
      intraductal hyperplasia.
AB  - Phyllodes tumor of the breast is a biphasic fibroepithelial neoplasm. 10 to 20%
      of phyllodes tumor show malignant transformation, often in the form of stroma,
      which usually shows fibrosarcomatous differentiation and rarely heterologous
      sarcomatous elements. Liposarcomatous differentiation is not common among
      phyllodes tumors. The correct diagnosis of heterologous liposarcomatous
      differentiation in a malignant PT requires identification of the biphasic
      component of the tumor. We reported a case of malignant phyllodes tumor which
      initially transformed into liposarcoma, in addition to a very rare intraductal
      hyperplasia and flat epithelial atypia. The patient was a 75-year-old woman, with
      a lump in the left breast without axillary lymphadenopathy. She also have a
      positive family history of breast carcinoma. She underwent surgery and still
      alive and disease free after one year. 

PMID- 25061021
TI  - Integrated imaging of breast hamartoma: two case reports.
AB  - Hamartoma of the breast is an uncommon, benign, slow-growing mass usually
      diagnosed in women in the fourth and fifth decade of life undergoing mammography
      (MX). Here we report two cases of hamartoma of the breast assessed by integrated
      MX, ultrasonography and magnetic resonance imaging (MRI) examination. Case 1 was
      an asymptomatic 47-year-old woman who had never been screened previously. A 90 mm
      mass was found in her left breast on MX. Case 2 was a 35-year-old woman with pain
      in her right breast where a 50 mm mass was found on MX. Both patients underwent
      MRI examination. Breast MRI is an adjunct to MX that can confirm hamartoma
      diagnosis and exclude rare malignant transformation. 

PMID- 25061022
TI  - Features of non-mass enhancing lesions detected on 1.5 T breast MRI: a radiologic
      and pathologic analysis.
AB  - BACKGROUND: With increased utilization of magnetic resonance imaging (MRI) of the
      breast in clinical practice, many non-mass lesions are being detected
      incidentally. Although MRI-guided biopsies are usually performed for these
      lesions, no clear guidelines exist to determine the management of these lesions.
      OBJECTIVE: The purpose of this study was to explore the pathological features of
      incidentally detected non-mass lesions on breast MRI to determine rates of
      malignancy and to assess the predictive value of kinetic enhancement curves for
      further characterization of these lesions as benign versus malignant. METHODS: A
      retrospective review was performed of all MRI-guided core needle biopsies done at
      our institution between January 2009 and January 2012. RESULTS: 172 consecutively
      biopsied lesions were identified. 43% of the lesions were non-mass lesions, out
      of which 74.3% were benign, whereas 14.9% and 10.8% of these lesions had
      malignant and atypical features, respectively. The most commonly encountered non
      mass malignant lesion was ductal carcinoma in situ, whereas the most frequently
      seen invasive non-mass lesion was invasive lobular carcinoma. Kinetic enhancement
      curves for these lesions did not demonstrate a statistically significant
      relationship with their pathologic features. CONCLUSIONS: Non-mass enhancing
      lesions incidentally detected on breast MRI carry a significant risk of atypia
      and malignancy, either in situ or invasive. Hence, it is prudent to biopsy these
      lesions.

PMID- 25061023
TI  - Continuum beliefs and attitudes towards people with mental illness: Results from
      a national survey in France.
AB  - BACKGROUND: Whether mental disorders should be considered as categorical or
      dimensional has found increasing attention among mental health professionals.
      Only little is known about what the public thinks about this issue. AIMS: First,
      to assess how prevalent the belief in a continuum of symptoms from mental health
      to mental illness is among the general public. Second, to examine how continuum
      beliefs are associated with attitudes towards people with mental disorder.
      METHODS: In 2012, an on-line survey was conducted in France (N = 1,600). After
      the presentation of a case-vignette depicting a person with either schizophrenia
      or depression, belief in a continuum of symptoms, emotional reactions and desire
      for social distance related to the person in the vignette were assessed. RESULTS:
      While 58.2% of respondents agreed in a symptom continuum for depression, this
      percentage was only 28.5% for schizophrenia. In both disorders, continuum beliefs
      were associated with more pro-social reactions and less desire for social
      distance. Only in schizophrenia, there was an inverse relationship with the
      expression of anger. CONCLUSIONS: There is increasing evidence of an association
      between continuum beliefs and positive attitudes towards people with mental
      illness. Information on the continuous nature of psychopathological phenomena may
      usefully be included in anti-stigma messages.

PMID- 25061024
TI  - Structured assessment of suicide risk in a psychiatric emergency service:
      Psychometric evaluation of the Nurses' Global Assessment of Suicide Risk scale
      (NGASR).
AB  - BACKGROUND: Risk of suicide is notoriously difficult to assess, and no gold
      standard is available, in terms of an instrument of first choice. Many different
      instruments are in use, among which are some that are not properly
      psychometrically investigated. AIM: The aim of this study is to establish the
      psychometric properties of the Dutch version of the Nurses' Global Assessment of
      Suicide Risk scale (NGASR), and the feasibility of its use in assessing suicide
      risk. Therefore, our research questions are as follows: what is the reliability,
      validity, interpretability and feasibility of the NGASR? METHODS: A psychometric
      study of acceptability, reliability and predictive validity among 252 patients
      making use of a concurrent instrument, the Suicide Intention Scale (SIS),
      concurrent assessment by a physician and 6-month follow-up. RESULTS: Factor
      analysis identified five factors. Cronbach's alpha was .45. Intraclass
      correlation was .92 (95% confidence interval (CI) = .85-.95). Association between
      total NGASR and SIS was substantial and significant (B = 0.66, standard error of
      mean (SE) = 0.19, beta = .66, p = .003). NGASR total score had a significant and
      moderately strong association with judgement by a physician on 'suicidal
      thoughts' (odds ratio (OR) = 1.24, p = < .001) or 'suicidal thoughts or plans'
      (OR = 1.35, p = .001). No significant association of NGASR scores and 6-month
      follow-up of suicidality was found. CONCLUSIONS: Internal consistency of the
      NGASR and most of the subscales identified was low. Other indicators of
      reliability of the NGASR were sufficient, although predictive validity was poor.
      The NGASR did not outperform other instruments but is easy to use, and may
      contribute to identification of risk factors, as well as to a more integral
      assessment of suicide risk.

PMID- 25061025
TI  - Clinical prediction models to inform individualized decision-making in subfertile
      couples: a stratified medicine approach.
AB  - Infertility is defined as failure to conceive after 1 year of unprotected
      intercourse. This dichotomization into fertile versus infertile, based on lack of
      conception over 12-month period, is fundamentally flawed. Time to conception is
      strongly influenced by factors such as female age and whilst a minority of
      couples have absolute infertility (sterility), many are able to conceive without
      intervention but may take longer to do so, reflecting the degree of subfertility.
      This natural variability in time to conception means that subfertility reflects a
      prognosis rather than a diagnosis. Current clinical prediction models in
      fertility only provide individualized estimates of the probability of either
      treatment-independent pregnancy or treatment-dependent pregnancy, but do not take
      account of both. Together, prognostic factors which are able to predict natural
      pregnancy and predictive factors of response to treatment would be required to
      estimate the absolute increase in pregnancy chances with treatment. This
      stratified medicine approach would be appropriate for facilitating personalized
      decision-making concerning whether or not to treat subfertile patients. Published
      models are thus far of little value for decisions regarding when to initiate
      treatment in patients who undergo a period of, ultimately unsuccessful, expectant
      management. We submit that a dynamic prediction approach, which estimates the
      change in subfertility prognosis over the course of follow-up, would be ideally
      suited to inform when the commencement of treatment would be most beneficial in
      those undergoing expectant management. Further research needs to be undertaken to
      identify treatment predictive factors and to identify or create databases to
      allow these approaches to be explored. In the interim, the most feasible approach
      is to use a combination of previously published clinical prediction models. 

PMID- 25061026
TI  - Cost of fertility treatment and live birth outcome in women of different ages and
      BMI.
AB  - STUDY QUESTION: What is the impact of different age and BMI groups on total
      investigation and treatment costs in women attending a secondary/tertiary care
      fertility clinic? SUMMARY ANSWER: Women in their early to mid-30s and women with
      normal BMI had higher cumulative investigation and treatment costs, but also
      higher probability of live birth. WHAT IS KNOWN ALREADY: Female age and BMI have
      been used as criteria for rationing publically funded fertility treatments.
      Population-based data on the costs of investigating and treating infertility are
      lacking. STUDY DESIGN, SIZE AND DURATION: A retrospective cohort study of 2463
      women was conducted in a single secondary/tertiary care fertility clinic in
      Aberdeen, Scotland from 1998 to 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Participants included all women living in a defined geographical area referred
      from primary care to a specialized fertility clinic over an 11-year period. Women
      were followed up for 5 years or until live birth if this occurred sooner. Mean
      discounted cumulative National Health Service costs (expressed in 2010/2011 GBP)
      of fertility investigations, treatments (including all types of assisted
      reproduction), and pregnancy (including delivery episode) and neonatal admissions
      were calculated and summarized by age (<= 30, 31-35, 36-40, >40 years) and BMI
      groupings (<18.50, 18.50-24.99 (normal BMI), 25.00-29.99, 30.00-34.99, >= 35.00
      kg/m(2)). Further multivariate modelling was carried out to estimate the impact
      of age and BMI on investigation and treatment costs and live birth outcome,
      adjusting for covariates predictive of the treatment pathway and live birth. MAIN
      RESULTS AND THE ROLE OF CHANCE: Of the 2463 women referred, 1258 (51.1%) had a
      live birth within 5 years, with 694 (55.1%) of these being natural conceptions.
      The live birth rate was highest among women in the youngest age group (64.3%),
      and lowest in those aged >40 years (13.4%). Overall live birth rates were
      generally lower in women with BMI >30 kg/m(2). The total costs of investigations
      were generally highest among women younger than 30 years (L491 in those with
      normal BMI), whilst treatment costs tended to be higher in 31-35 year olds
      (L1,840 in those with normal BMI). Multivariate modelling predicted a cost
      increase associated with treatment which was highest among women in the lowest
      BMI group (across all ages), and also highest among women aged 31-35 years. The
      increase in the predicted probability of live birth with exposure to treatment
      was consistent across age and BMI categories (~ 10%), except in the oldest age
      group where a slightly smaller increase in the probability of live birth was
      observed. The ratio of increased costs to the increased probability of live birth
      in women who were treated increased markedly in women over the age of 40 years,
      but tended to fall as BMI increased within all age groups. LIMITATIONS AND REASON
      FOR CAUTION: Our results, based on retrospective observational data from a single
      centre, have limited generalizability and are not free from clinician and clinic
      selection bias which can influence the choice of treatments as well as their
      costs. WIDER IMPLICATIONS OF THE FINDINGS: Spontaneous live birth rates were
      particularly high in younger women with unexplained infertility, suggesting that
      expectant management is a reasonable option in this group. The policy of not over
      investigating older women and offering early treatment where appropriate still
      incurred the highest costs per additional live birth associated with treatment,
      owing to the lower probability of treatment success. The increased additional
      cost for each live birth associated with treatment for women with decreasing BMI
      across all age groups, suggests that it may be possible to identify a more
      targeted approach to treatment. STUDY FUNDING/COMPETING INTERESTS: This study was
      partly funded by an NHS endowment grant (Grant Number 12/48) and D.J.M. by a
      Chief Scientist Office Postdoctoral Fellowship (Ref PDF/12/06). There are no
      conflicts of interest to declare.

PMID- 25061027
TI  - Age of menarche and time to pregnancy.
AB  - STUDY QUESTION: Is age of menarche (AOM) associated with subfecundity and/or
      infertility in adulthood? STUDY ANSWER: A late onset of menarche was associated
      with a slightly increased risk of subfecundity and infertility. WHAT IS KNOWN
      ALREADY: Abnormal age at onset of menarche is a risk factor for several diseases
      later in life, but the effect on infertility is unknown. STUDY DESIGN, SIZE AND
      DURATION: A cohort study of  73 107 pregnant Danish women enrolled in the Danish
      National Birth Cohort (DNBC) between 1996 and 2002 with self-reported data on AOM
      and waiting time to pregnancy (TTP). PARTICIPANTS/MATERIALS, SETTING AND METHODS:
      Information on AOM and TTP was collected through a computer-assisted telephone
      interview scheduled in pregnancy Week 12. We estimated adjusted odds ratios (ORs)
      with 95% confidence intervals (CIs) using multivariate logistic regression with
      TTP categorized as subfecundity (TTP >=6 months) and infertility (TTP >12
      months). Multiple imputation was performed to account for missing data. MAIN
      RESULTS AND THE ROLE OF CHANCE: We found trends towards higher odds of
      subfecundity and infertility with increasing age of menarche, using 13 years as
      the starting point. Among women reaching menarche at 15 years, the odds for
      subfecundity were 1.09 (95% CI: 1.03-1.15), and 1.17 (95% CI: 1.09-1.25) for
      women reaching menarche later than 15 years compared with the reference group of
      girls reaching menarche at 13 years. Additionally, women reaching menarche older
      than 15 years had an OR of infertility of 1.18 (95% CI: 1.08-1.29). Women younger
      than 11 years at menarche had lower odds of subfecundity. The results were
      generally attenuated when adjusting for women's age of pregnancy, but the
      significant positive trend of higher OR for subfecundity persisted, as did the
      higher OR for subfecundity among women experiencing menarche older than 15 years.
      LIMITATIONS, REASONS FOR CAUTION: We used retrospectively collected self-reported
      information on AOM and TTP. Information on male factors was limited in this
      cohort. We only included pregnant women and have therefore no data on women with
      untreated and unsuccessfully treated infertility, limiting the generalizability
      to women who became pregnant. WIDER IMPLICATION OF THE FINDINGS: This study
      indicates that the onset of menarche at 15 years or later is associated with
      subfecundity and infertility. STUDY FUNDING/COMPETING INTERESTS: The Danish
      National Research Foundation has established the Danish Epidemiology Science
      Centre that initiated and created the DNBC. The cohort is furthermore a result of
      a major grant from this Foundation. Additional support for the DNBC is obtained
      from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth
      Defects Foundation, the Augustinus Foundation and the Health Foundation. This
      specific study was supported by a scholarship from the Ministry of Science and
      Innovation. No conflict of interest declared.

PMID- 25061028
TI  - A comparison of acute effects between    Kinesio tape and electrical muscle
      elongation   in hamstring extensibility.
AB  - BACKGROUND: To improve hamstring extensibility some methods have been analyzed
      and compared for determining their acute and chronic effectiveness. OBJECTIVE: To
      compare the immediate effect of electrical muscle elongation (EME) versus Kinesio
      tape (KT) in hamstring muscle extensibility. METHODS: One hundred and twenty
      adult amateur athletes with hamstring shortness (straight leg raise test angle
      <80?) were randomly assigned to a group: group 1 (EME session of 4 KHz
      interferential current, bipolar technique and AMF = 100 Hz, n = 40), group 2 (KT,
      n = 40) or group 3 (control group, no intervention, n = 40). Hamstring
      extensibility was assessed before and after the intervention through the active
      knee extension test. Results: Significant improvements were found in both EME and
      KT groups whereas no changes were detected in the control group. However, no
      significant differences between both techniques were detected. The EME group
      showed large effect size (d = 0.843) while the KT group reached medium effect
      size (d = 0.431). CONCLUSIONS: Both electrical muscle elongation and Kinesio tape
      are effective techniques in the short-term in amateur athletes with decreased
      hamstring extensibility. The higher increase of hamstring extensibility, with a
      better clinical effect was achieved with the application of electrical muscle
      elongation. However, no significant differences were found when comparing the
      effectiveness of both techniques.

PMID- 25061029
TI  - MMPI-2 profiles and illness perception in   fibromyalgia syndrome: The role of  
      therapeutic exercise as adapted physical   activity.
AB  - BACKGROUND: Control of pain management is an important up-stream process in
      fibromyalgia (FM) mechanisms. OBJECTIVE: To investigate whether adapted physical
      activity (APA) could change the illness perception in relation to the FM
      personality profile. METHODS: Thirty-seven women with FM allocated randomly: 19
      treatment group (TG) and 18 control group (CG). Interventions: exercises program
      included ten sessions, two times for week for one hour each and observation for
      CG. Scales: Illness Perception Questionnaire-revisited (IPQ-r) for the mental
      representation of the disease, Minnesota Multiphasic Personality Inventory
      profiles (MMPI-2) for personality tool and Fibromyalgia Impact Questionnaire
      (FIQ) for function, impact and symptoms. Outcome assessments were performed
      before rehabilitation treatment (T0) than at the end (T1), and a follow-up 12
      weeks after treatment (T2). RESULTS: APA was efficacy to improve FIQ values in TG
      at T1 and T2 test days (P = 0.014). Changes in IPQ-R values in T2 were not
      significant. All patients presented a baseline T-score>=65 in at least one of the
      basic and content MMPI-2 scales (Hy, D, Hs and Hea and Anx). CONCLUSION: APA was
      efficacy in FM, but further research to differentiate between illness experience
      rather than focus ona strict personality profile are necessary.

PMID- 25061030
TI  - Relationship between standing postural   alignments and physical function among  
      elderly women using day service centers in   Japan.
AB  - BACKGROUND: Posture and physical function have been quantified in mature adults,
      but not in elderly females. OBJECTIVE: To quantify standing posture and measures
      of physical function in community-dwelling women over the age of 65 years, and to
      examine relationships between these variables. METHODS: Fifty-three women were
      recruited from day care service users (average age: 83.7 +/-6.3 years old).
      Standing postural alignments were assessed using 2-dimensional analyses with a
      digital video camera. The time up and go test (TUG) and other physical function
      tests were conducted. RESULTS: Decreased lower cervical angle (increased forward
      head position) was significantly correlated with increased upper cervical angle
      (increased chin-up, r = -0.45), increased thoracic spine angle (increased
      kyphosis, r = -0.38), and decreased lumbar spine angle (thoracolumbar segments
      backward relative to the pelvis, r = 0.48). The decreased lumbar spine angle was
      significantly correlated with increased thoracic angle (increased kyphosis, r = 
      0.37), increased pelvic plane angle (increased anterior pelvic tilt, r = -0.49),
      and decreased knee flexion angle (r = 0.46). Increased TUG time (slower walking
      speed) was correlated to increased forward head position (r = 0.30) and
      thoracolumbar segments forward relative to the pelvis (r = 0.34). CONCLUSIONS:
      Posture and physical function measures were provided for community-dwelling
      females who were >65 years of age. They did not demonstrate any correlation
      between measured knee strength, back strength or single leg standing with
      measures of postural alignment, but TUG showed a moderate correlation with the
      lower cervical and lumbar spine posture measures.

PMID- 25061031
TI  - Effects of intra-articular application of pulsed   radiofrequency on pain,
      functioning and   quality of life in patients with advanced knee  
      osteoarthritis.
AB  - BACKGROUND AND OBJECTIVE: The number of studies and evidences is inadequate
      especially with regard to the efficacy of pulsed radiofrequency (PRF) application
      in non-spinal indications. The purpose of this study was to investigate the
      effect of PRF on pain, functioning and quality of life in patients with advanced
      knee OA. METHODS: The study included 21 patients with complaints of knee pain.
      Intra-articular PRF was applied for 10 minutes at 42?C. Pain severity was
      assessed using the 10 cm standard visual analogue scale (VAS). Outcome measures
      also included a 20-meter walk test, a 6-minute walk test, WOMAC, Lequesne index,
      and the Short Form-36 (SF-36). All measurements were assessed before treatment
      and 4 and 12 weeks after the treatment. RESULTS: A statistically significant
      improvement was found in VAS scores at rest and after walking, subscores of SF36
      pain and SF36-social functioning, and Lequesne score at week four (p < 0.05).
      This improvement was maintained for the scores of VAS-walking at week 12 (p <
      0.05). CONCLUSION: It is possible to state that intra-articular PRF application
      is effective and safe for the pain treatment of patients with advanced knee OA.
      Therefore, we think that PRF application will be included in chronic pain
      treatment guidelines in the future with the increase in the number of future
      studies.

PMID- 25061032
TI  - A note of caution with respect to the Low Back Pain Perception Scale in primary
      care physiotherapy.
AB  - BACKGROUND: The predictive validity of the Low Back Pain Perception Scale is
      determined in two studies in general practice and showed sufficient
      discriminative ability, although the psychometric properties of the scale have
      never been established until now. OBJECTIVE: To determine the reliability and
      validity of the Low Back Pain Perception Scale in acute nonspecific low back pain
      patients. METHODS: The Low Back Pain Perception Scale has been authorized
      translated into Dutch by two bilingual content experts. A sample of 84 acute low
      back pain patients in physiotherapy primary care, mean age (SD) age 42 (12) years
      participated in this study. Internal reliability and a test-retest procedure
      within one-week interval were evaluated. RESULTS: The internal consistency
      Cronbach alpha=0.38 (95% CI 0.09 to 0.56) and test - retest reliability within
      one week Intra Class Correlation coefficient=0.50 (95% CI 0.31 to 0.64). Minimal
      Detectable Change was measured 1.95. The concurrent validity demonstrates
      Pearson's r=0.35 (95% CI 0.14 to 0.53). CONCLUSIONS: The Low Back Pain Perception
      Scale demonstrates poor internal consistency and reliability and moderate
      concurrent validity. Extreme high or low scores may be clinical relevant
      therefore the scale can be used as a first screening instrument.

PMID- 25061033
TI  - Predicting low back pain outcome following  rehabilitation for low back pain.
AB  - BACKGROUND: Psychosocial factors are known to play a key role in determining the
      progress of back pain patients. However, it is not known whether these factors
      are applicable to military personnel, who tend to be fitter than the general
      population. OBJECTIVE: The aim was to identify physical and psychological
      predictors in a prospective study of the outcome of back pain rehabilitation over
      6 months and a longer follow-up time of between 15 and 32 months. METHODS: Two
      hundred and fifty military personnel reporting for a residential rehabilitation
      programme completed a battery of physical and psychological tests. The physical
      tests included 800 m run time and the Biering-Sorensen test. The
      psychological/psychosocial measures included items on fear avoidance, self
      efficacy, anxiety and depression and occupational psychosocial factors such as
      job satisfaction. RESULTS: Self efficacy and 800 m run time predicted self
      reported functional ability at 6 months and medical discharge/return to full
      fitness at 15-32 months. Patients with 800 m run times of more than 3 minutes 31
      seconds had a four times greater chance of medical discharge from the Armed
      forces. CONCLUSIONS: Eight hundred metre run time and self-efficacy were
      independent predictors of both self-reported functional ability at 6 months and
      return to full fitness/medical discharge at 15-32 months. Self-efficacy also
      predicted 40% of the variance in the intensity of back pain and 10% of other non
      back pain. Rehabilitation should include greater emphasis on physical fitness and
      on improving self-efficacy.

PMID- 25061034
TI  - Efficacy of low level laser therapy and   intramuscular electrical stimulation on
      myofascial pain syndrome.
AB  - BACKGROUND: Myofascial pain syndrome (MPS) which is an important cause of
      musculoskeletal pain has shown a dramatic increase in recent years. OBJECTIVES:
      We aimed to evaluate the efficacy of intramuscular electrical stimulation therapy
      (IMS) and low-level-lasertherapy (LLLT) in patients with MPS. METHODS: Patients
      were randomly divided into three groups. First group were treated with LLLT and
      stretching exercise. Second group were treated with IMS and stretching exercise.
      Third group were treated with only stretching exercise. The patients were
      evaluated through the pain intensity, pain threshold, cervical joint movement
      range and the neck disability index parameters. RESULTS: An improvement was found
      in all parameters for all groups, except for the pain threshold within the
      control group at the end of the treatment and one month after the treatment. It
      was found that pain score was significantly lower in Group 1 and 2 at one month
      after the treatment compared to Group 3. Similarly, it was found that pain
      threshold score was significantly higher in Group 2 at one month after the
      treatment compared to Group 3. CONCLUSIONS: In this study we observed that both
      LLLT and IMS treatments added on to stretching are effective in improving pain
      parameters in patients with MPS.

PMID- 25061035
TI  - Measurement precision for Oswestry Back   Pain Disability Questionnaire versus a 
      web-based computer adaptive testing for   measuring back pain.
AB  - BACKGROUND AND OBJECTIVES: Relative precision is to denote the ratio of the error
      variance of two sample designs. The aim of the present study was to compare
      measurement precisions of the Oswestry Back Pain Disability Questionnaire and a
      computer adaptive testing (CAT) method for measuring disability resulting from
      back pain. MATERIAL AND METHOD: A cross-sectional study was carried out with two
      independent convenient samples from two out-patient rehabilitation clinics for
      back pain (N = 42) and non-back pain groups (N = 42). Participants were asked to
      fill out the ODQ and CAT of International Classification of Functioning,
      Disability and Health - Activity Measure (ICF-AM). A series of Rasch analyses
      were performed to calculate person ability measures. RESULTS: The CAT measures
      had greater precision in discriminating the groups than did the ODQ measure in
      comparisons of the relative precision. CONCLUSIONS: The CAT measure appears to be
      more effective than the ODQ measure in terms of measurement precision. By
      administering test items calibrated in a way, CAT measures using item response
      theory may promise a means with measurement precision as well as efficiency.

PMID- 25061036
TI  - The influence of handlebar-hands position on   spinal posture in professional
      cyclists.
AB  - BACKGROUND AND OBJECTIVE: Systematic repetition or prolonged posture in specific
      postures adopted during training could generate modifications on the sagittal
      spinal curvatures. Spinal alteration in its physiologic curvatures in the
      sagittal plane has been associated with predisposition to spinal disorders. The
      objective was to evaluate and compare the changes produced on the sagittal
      thoracic and lumbar spinal curvatures, and pelvic tilt from standing posture on
      the floor to upper, middle, lower and aerodynamic handlebars postures adopted on
      their own road bicycles. MATERIAL AND METHOD: A total of twenty-eight male
      professional cyclists (179.92 +/- 5.78 cm; 67.18 +/- 5.74 kg) participated in the
      study. Cyclists had an experience of 17.22 +/- 6.16 years in cycling, and spent
      6.52 +/- 0.51 days per week and 3.78 +/- 0.61 hours per day training on their
      bicycles. Sagittal spinal curvatures (thoracic and lumbar) and pelvic tilt were
      measured in the standing position on the floor and while sitting on a bicycle
      with different handlebar-hand positions (high, middle, low and aerodynamic) using
      a Spinal Mouse system. RESULTS: The thoracic spine showed significantly greater
      angular values while in a standing posture than on the bicycle in all handlebar
      hands postures evaluated. The lumbar curvature changed from lordosis (negative
      values - anterior convexity) in standing posture to kyphosis (positive values -
      posterior convexity) in all handlebar-hands positions on the bicycle. The
      aerodynamic handlebar positions showed the greatest lumbar flexion (lumbar
      kyphosis) and anterior pelvic tilt. CONCLUSIONS: Professional cyclists passively
      maintain their thoracic spine straighter on the bicycle due to handlebar-hands
      support than in standing posture. However, the lumbar spine is flexed on the
      bicycle in all handlebar-hands evaluated. The pelvis is modified to greater
      anterior pelvic tilt when the handlebar-hands position is farther and lower
      regarding the saddle of the bicycle.

PMID- 25061037
TI  - Spinal postural training: Comparison of the   postural and mobility effects of  
      electrotherapy, exercise, biofeedback trainer   in addition to postural education
      in university   students.
AB  - BACKGROUND AND OBJECTIVE: Spinal posture and mobility are significant for
      protecting spine. The aim was to compare effects of different postural training
      interventions on spinal posture and mobility. MATERIAL AND METHOD: Ninety-six
      university students (ages: 18-25 years) were allocated into Electrical
      Stimulation (ES) (n = 24), Exercise (n = 24), Biofeedback Posture Trainer
      (Backtone) (n = 24), and Postural Education (n = 24, Controls) groups. All the
      groups got postural education. The interventions were carried out 3 days a week
      for 8 weeks. Spinal Mouse device (Idiag, Fehraltorf, Switzerland) was used to
      detect thoracic and lumbar curvatures and mobility (degrees) in standing and
      sitting positions. Paired Student's t-test, one-way ANOVA, and pairwise post-hoc
      tests were used. RESULTS: ES decreased thoracic curvature, the exercise decreased
      thoracic and lumbar curvature and increased thoracic mobility in standing
      position between pre-post training (p < 0.05). Exercise and Backtone improved
      thoracic curvature in sitting (p <0.05). In Exercise Group, thoracic curvature
      decreased compared to Backtone and Education Groups, and thoracic mobility
      increased compared to all groups (p < 0.05). CONCLUSIONS: The exercise was
      effective and superior in improving thoracic and lumbar curves, and mobility
      among university students. ES decreased thoracic curve. Biofeedback posture
      trainer improved sitting posture. LEVEL OF EVIDENCE: A prospective randomized
      controlled trial, Level 1.

PMID- 25061038
TI  - Short-term effectiveness of short-wave diathermy treatment on pain, clinical
      symptoms, and hand function in patients with mild or moderate idiopathic carpal
      tunnel syndrome.
AB  - OBJECTIVE: We determined the effects of short-wave diathermy (SWD) treatment on
      mild and moderate idiopathic carpal tunnel syndrome (CTS). METHODS: This was a
      prospective, randomized, controlled, double-blind clinical trial. The study
      involved 58 wrists in 31 patients diagnosed clinically and electrophysiologically
      with mild and moderate CTS. They were assigned randomly to one of two groups.
      Group 1 received a hot pack, SWD, and nerve and tendon gliding exercises and
      Group 2 received a hot pack, placebo SWD, and nerve and tendon gliding exercises.
      The treatment was applied five times weekly for a total of 15 sessions. Patients
      were evaluated using the Tinel test, Phalen test, carpal compression test,
      reverse Phalen test, carpal tunnel compression test, Boston Carpal Tunnel
      Questionnaire (BCTQ) Symptom Severity Scale (SSS), Functional Status Scale (FSS),
      and a visual analog scale (VAS). Clinical tests and scales were evaluated at the
      beginning and end of therapy. RESULTS: In the SWD group, in the Tinel test,
      Phalen test, reverse Phalen test, carpal compression test, VAS, BCTQ-FSS, and
      BCTQ-SSS, statistically significant improvements were detected (p < 0.001). In
      the placebo group, although improvements were seen in all parameters, the results
      were not statistically significantly different (p > 0.05) from baseline. All
      parameters improved significantly in the SWD group versus the controls (p <
      0.05). CONCLUSION: SWD provided short-term improvements in pain, clinical
      symptoms, and hand function in patients with mild and moderate CTS.

PMID- 25061040
TI  - Transcriptional dynamics of developmental genes assessed with an FMN-dependent
      fluorophore in mature heterocysts of Anabaena sp. strain PCC 7120.
AB  - Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that differentiates
      nitrogen-fixing heterocysts when available combined nitrogen is limiting. Growth
      under diazotrophic conditions results in a mixture of 'new' (recently
      differentiated) and 'old' (mature) heterocysts. The microoxic environment present
      in heterocysts makes the interpretation of gene expression using oxygen-dependent
      fluorophores, including GFP, difficult. The work presented here evaluates the
      transcriptional dynamics of three developmental genes in mature heterocysts
      utilizing EcFbFP, a flavin mononucleotide-dependent fluorophore, as the reporter.
      Expression of both GFP and EcFbFP from the heterologous petE promoter showed
      that, although GFP and EcFbFP fluoresced in both vegetative cells and new
      heterocysts, only EcFbFP fluoresced in old heterocysts. A transcriptional fusion
      of EcFbFP to the late-stage heterocyst-specific nifB promoter displayed continued
      expression beyond the cessation of GFP fluorescence in heterocysts. Promoter
      fusions of the master regulator of differentiation, hetR, and its inhibitors,
      patS and hetN, to GFP and EcFbFP were visualized to determine their role(s) in
      heterocyst function after morphogenesis. The expression of hetR and hetN was
      found to persist beyond the completion of development in most heterocysts,
      whereas patS expression ceased. These data are consistent with a model of
      heterocyst patterning in which patS is involved in de novo pattern formation,
      hetN is required for pattern maintenance, and hetR is needed for all stages of
      development. 

PMID- 25061039
TI  - Increased expression of GAP43 in interneurons in a rat model of experimental
      polymicrogyria.
AB  - To investigate seizure susceptibility in polymicrogyria, the seizure threshold
      and growth-associated protein GAP43 expression were analyzed in a rat
      experimental model of polymicrogyria induced by intracerebral injection of
      ibotenate. A total of 72 neonates from 9 pregnant rats were used. Intraperitoneal
      pentylenetetrazole injection did not induce any seizure activity in the control
      rats, although it elicited seizures of variable severity in the polymicrogyria
      rats. Fluoro-Jade B-positive degenerating interneurons were found in the
      polymicrogyria brains; however, no such neurons were detected in the control
      brains. In the polymicrogyria rats, the GAP43 expression was significantly and
      widely distributed in the brain, and the percentage of parvalbumin-positive
      interneurons in the GAP43-positive cells was significantly higher than that
      observed in the nonphosphorylated neurofilament-positive pyramidal cells. We
      conclude that the relatively selective vulnerability of inhibitory interneurons
      constitutes the basis for the decreased seizure threshold observed in this model
      of polymicrogyria. 

PMID- 25061041
TI  - A cAMP-independent carbohydrate-driven mechanism inhibits tnaA expression and
      TnaA enzyme activity in Escherichia coli.
AB  - When Escherichia coli is grown in a medium lacking glucose or another preferred
      carbohydrate, the concentration of cAMP-cAMP receptor protein (cAMP-CRP)
      increases, and this latter complex regulates the expression of more than 180
      genes. To respond rapidly to changes in carbohydrate availability, E. coli must
      maintain a suitable intracellular concentration of cAMP by either exporting or
      degrading excess cAMP. Currently, cAMP export via the TolC protein is thought to
      be more efficient at reducing these levels than is CpdA-mediated degradation of
      cAMP. Here, we compared the contributions of TolC and CpdA by measuring the
      expression of cAMP-regulated genes that encode tryptophanase (TnaA) and beta
      galactosidase. In the presence of exogenous cAMP, a tolC mutant produced
      intermediate levels of these enzymes, suggesting that cAMP levels were held in
      check by CpdA. Conversely, a cpdA mutant produced much higher amounts of these
      enzymes, indicating that CpdA was more efficient than TolC at reducing cAMP
      levels. Surprisingly, expression of the tnaA gene halted rapidly when glucose was
      added to cells lacking both TolC and CpdA, even though under these conditions
      cAMP could not be removed by either pathway and tnaA expression should have
      remained high. This result suggests the existence of an additional mechanism that
      eliminates intracellular cAMP or terminates expression of some cAMP-CRP-regulated
      genes. In addition, adding glucose and other carbohydrates rapidly inhibited the
      function of pre-formed TnaA, indicating that TnaA is regulated by a previously
      unknown carbohydrate-dependent post-translational mechanism. 

PMID- 25061042
TI  - Structure and gene cluster of the O antigen of Escherichia coli L-19, a candidate
      for a new O-serogroup.
AB  - Escherichia coli L-19 isolated from a healthy individual did not agglutinate with
      any of 21 polyvalent antisera that cover 174 E. coli O-serogroups. The strain was
      studied in respect to the O-antigen (O-specific polysaccharide, OPS) structure
      and genetics. The LPS was isolated by phenol-water extraction of bacterial cells
      and cleaved by mild acid hydrolysis to yield the OPS. The OPS was studied by
      sugar and methylation analyses, along with 1D and 2D (1)H and (13)C NMR
      spectroscopy. The established structure of the linear tetrasaccharide repeating
      unit was found to be unique among known bacterial polysaccharide structures. A
      peculiar component of the L-19 OPS was an amide of glucuronic acid with 2-amino
      1,3-propanediol (2-amino-2-deoxyglycerol) (GroN). The O-antigen gene cluster of L
      19 between the conserved genes galF and gnd was sequenced, and gene functions
      were tentatively assigned by a comparison with sequences in the available
      databases and found to be in agreement with the OPS structure. Except for
      putative genes for synthesis and transfer of GroN, the sequences in the L-19 O
      antigen gene cluster were little related to those of reference strains of the 174
      known E. coli O-serogroups. The data obtained suggest that L-19 can be considered
      as a candidate for a new E. coli O-serogroup. 

PMID- 25061043
TI  - Sro7 and Sro77, the yeast homologues of the Drosophila lethal giant larvae (Lgl),
      regulate cell proliferation via the Rho1-Tor1 pathway.
AB  - Saccharomyces cerevisiae Sro7 and Sro77 are homologues of the Drosophila tumour
      suppressor lethal giant larvae (Lgl), which regulates cell polarity in Drosophila
      epithelial cells. Here, we showed that double mutation of SRO7/SRO77 was
      defective in colony growth. The colony of the SRO7/SRO77 double deletion was much
      smaller than the WT and appeared to be round with a smooth surface, compared with
      the WT. Analysis using transmission electron microscopy revealed multiple defects
      of the colony cells, including multiple budding, multiple nuclei, cell lysis and
      dead cells, suggesting that the double deletion caused defects in cell polarity
      and cell wall integrity (CWI). Overexpression of RHO1, one of the central
      regulators of cell polarity and CWI, fully recovered the sro7Delta/sro77Delta
      phenotype. We further demonstrated that sro7Delta/sro77Delta caused a decrease of
      the GTP-bound, active Rho1, which in turn caused an upregulation of TOR1.
      Deletion of TOR1 in sro7Delta/sro77Delta (sro7Delta/sro77Delta/tor1Delta)
      recovered the cell growth and colony morphology, similar to WT. Our results
      suggested that the tumour suppressor homologue SRO7/SRO77 regulated cell
      proliferation and yeast colony development via the Rho1-Tor1 pathway. 

PMID- 25061044
TI  - Terrestrial locomotion-where do we stand, where are we going? An introduction to
      the symposium.
AB  - Locomotion is fundamental to the survival of many animal species, and terrestrial
      environments are one of the primary habitats through which a wide range of
      animals (including humans) must move. Many recent efforts have been made to
      broaden the approaches and systems used to understand how terrestrial locomotion
      is executed and modulated. This symposium highlights these efforts and seeks to
      identify new directions for the study of this diverse behavior. Studies focusing
      on the structural and functional foundations of terrestrial locomotion,
      terrestrial locomotor dynamics, and terrestrial locomotor diversity point toward
      several promising areas for future work. These include: the development,
      application, and refinement of computational and robotic models; the integration
      of approaches to clarify which of multiple layers of selection and biological
      organization influence locomotor performance; increasing the taxonomic,
      environmental, and behavioral range of study systems to promote new research
      syntheses and questions; and expansion of studies from laboratory settings to
      examinations in the field and in the context of ontogenetic and evolutionary
      time. With new, integrative data from diverse systems in natural settings, new
      opportunities will emerge for understanding how locomotion contributes to the
      survival and fitness of terrestrial animals. 

PMID- 25061045
TI  - Features and machine learning classification of connected speech samples from
      patients with autopsy proven Alzheimer's disease with and without additional
      vascular pathology.
AB  - Mixed vascular and Alzheimer-type dementia and pure Alzheimer's disease are both
      associated with changes in spoken language. These changes have, however, seldom
      been subjected to systematic comparison. In the present study, we analyzed
      language samples obtained during the course of a longitudinal clinical study from
      patients in whom one or other pathology was verified at post mortem. The aims of
      the study were twofold: first, to confirm the presence of differences in language
      produced by members of the two groups using quantitative methods of evaluation;
      and secondly to ascertain the most informative sources of variation between the
      groups. We adopted a computational approach to evaluate digitized transcripts of
      connected speech along a range of language-related dimensions. We then used
      machine learning text classification to assign the samples to one of the two
      pathological groups on the basis of these features. The classifiers' accuracies
      were tested using simple lexical features, syntactic features, and more complex
      statistical and information theory characteristics. Maximum accuracy was achieved
      when word occurrences and frequencies alone were used. Features based on
      syntactic and lexical complexity yielded lower discrimination scores, but all
      combinations of features showed significantly better performance than a baseline
      condition in which every transcript was assigned randomly to one of the two
      classes. The classification results illustrate the word content specific
      differences in the spoken language of the two groups. In addition, those with
      mixed pathology were found to exhibit a marked reduction in lexical variation and
      complexity compared to their pure AD counterparts. 

PMID- 25061047
TI  - The Montreal Cognitive Assessment in cognitively-intact elderly: a case for age
      adjusted cutoffs.
AB  - The Montreal Cognitive Assessment (MoCA) is a widely used screening test for
      evaluation of mild cognitive impairment (MCI), with a single cutoff for all ages.
      We examined whether it is associated with age in a sample of cognitively-intact
      elderly (CIE). The average MoCA score was negatively correlated with age and was
      significantly higher for younger than older CIE. Additionally, 42% of the older
      elderly fell below the proposed MCI cutoff score, although all subjects were CIE.
      Thus, cognitive abilities captured by the MoCA test decrease with age, even in
      CIE. Therefore, cutoff scores by age for the MoCA are needed. 

PMID- 25061046
TI  - Abeta1-17 is a major amyloid-beta fragment isoform in cerebrospinal fluid and
      blood with possible diagnostic value in Alzheimer's disease.
AB  - This work was prompted by the finding that Abeta1-17 (Abeta17) appeared to be the
      second-most abundant cerebrospinal fluid (CSF) Abeta fragment, after Abeta40. We
      developed an ELISA to quantify levels of Abeta17 directly accessible in plasma
      (DA17), recovered from the proteomic plasma matrix (RP17) and associated with the
      cellular pellet (CP17) that remained after plasma collection. Then, we used a
      sample of 19 healthy control (HC), 27 mild cognitive impairment (MCI), and 17
      mild Alzheimer's disease (AD) patients to explore the association of the
      diagnostic groups with those direct markers, their ratios or the ratios with
      their Abeta40 or Abeta42 counterparts. After dichotomization (d) for the median
      of the sample population, logistic regression analysis showed that in the AD
      versus HC subgroup, subjects with a dDA/CP17 higher than the median had a
      significantly greater risk of being AD than those with marker levels equal to or
      below the median (odds ratio OR; 95% confidence interval; 17.21; 1.42-208.81).
      Subjects with dRP17/42 below the median had an increased likelihood of being MCI
      (20.00; 1.17-333.33) or AD (40.00; 1.87-1000) versus being HC, than those with
      dRP17/42 higher than the median. Although the confidence intervals are wide,
      these findings suggest that assessment of Abeta17 may increase the diagnostic
      performance of blood-based Abeta tests which might be developed into minimally
      invasive first-step screening tests for people with increased risk for AD. 

PMID- 25061048
TI  - Presence and release of ATP from the retina in an Alzheimer's disease model.
AB  - The aim of this study was to assess the changes of extracellular ATP levels
      during the progress of Alzheimer's disease by using a murine model of the
      disease. Retinal nucleotide release was measured from flattened whole-mounts
      stimulated with 59 mM KCl or non-stimulated maintained in Ringer solution. Mice
      exhibited an increase in retinal ATP release as long as the pathology progressed
      up to 14 months. This value decreased to normal values by 18 months of age.
      Changes occurred also when comparing to non-pathological mice. The increase in
      the presence of ATP levels may contribute, together with other factors, to the
      changes in the functionality of the retina and the concomitant death of retinal
      cells. 

PMID- 25061049
TI  - Effectiveness and cost-effectiveness of the pharmacological treatment of
      Alzheimer's disease and vascular dementia.
AB  - Until an effective and especially disease-modifying treatment for Alzheimer's
      disease (AD) and vascular dementia (VaD) is available, the currently available
      pharmacological therapeutic arsenal aims at merely improving symptomatology.
      Health economic data make an important contribution to the planning of healthcare
      services and the estimation of the cost of drug reimbursement. As such, both for
      cholinesterase inhibitors and, to a lesser extent, for memantine it can be
      claimed that the direct cost of the drug itself is eclipsed by the cost savings
      associated with delaying institutionalization or delaying the time of progression
      into a more severe disease state. The present manuscript reviews several factors
      contributing to the costs of dementia, gives an overview of available studies
      claiming both the effectiveness and cost-effectiveness of current dementia
      treatments, and highlights strengths and weaknesses of the aforementioned
      studies. 

PMID- 25061050
TI  - High levels of homocysteine results in cerebral amyloid angiopathy in mice.
AB  - High levels of homocysteine is a risk factor for developing Alzheimer's disease
      (AD), and the effect that this amino acid has on amyloid-beta (Abeta) protein
      precursor metabolism is considered one of the potential mechanism(s) involved in
      this effect. However, despite consistent literature indicating that this
      condition results in brain parenchyma amyloidosis, no data are available on
      whether it may also influence the amount of Abeta deposited in the vasculature.
      To test this hypothesis, we implemented a model of diet-inducing high
      homocysteinemia in AD transgenic mice, 3xTg, and assessed them for the
      development of cerebral amyloid angiopathy (CAA). Compared with controls, mice
      with high homocysteine showed a significant increase in the amount of Abeta
      deposited in the brain vasculature, which was not associated with histological
      evidence of microhemorrhage occurrence. Mice with high homocysteine had a
      significant reduction in steady state level of the apolipoprotein E, which is a
      main Abeta chaperon protein, but no changes in its receptor, the low-density
      lipoprotein-receptor-1. Our data demonstrate that a diet-induced high
      homocysteine level favors the development of CAA via a reduction of Abeta
      clearance and transport within the brain. Therapeutic approaches aimed at
      restoring brain apolipoprotein E levels should be considered in individuals
      carrying this environmental risk factor in order to reduce the incidence of
      homocysteine-dependent CAA. 

PMID- 25061051
TI  - MPTP/MPP+ suppresses activation of protein C in Parkinson's disease.
AB  - Endothelial dysfunction and disruption of the blood-brain barrier have been found
      to be associated with Parkinson's disease (PD). However, the mechanisms
      underlying these effects have yet to be elucidated. It has also been found that
      activated protein C (APC) displays neuroprotective properties. Presently, the
      effects of APC on PD remain unknown. Using a 1-methyl-4-phenyl-1, 2, 3, 6
      tetrahydropyridine (MPTP) neurotoxin rodent model of PD, we found that
      administration of MPTP can reduce expression of endothelial protein C receptor
      (EPCR), an N-glycosylated type I membrane protein that has the ability to enhance
      protein C activation. However, the use of MPTP does not alter levels of
      thrombomodulin. These findings were verified in an in vitro study showing that 1
      methyl-4-phenylpyridinium (MPP+) treatment leads to suppression of EPCR along
      with reduction of protein C activation in human primary endothelial cells.
      Importantly, our results display that activation of the transcriptional factor
      SP1 is involved in the inhibitory effects of MPTP/MPP+ on EPCR expression. We
      found that using 300 nM of the SP1 inhibitor MIT can abolish the effects of MPP+
      on EPCR expression. Consistently, SP1 silencing using small RNA interference was
      able to prevent the inhibitory effects of MPTP/MPP+ on the reduction of EPCR
      expression and impairment of protein C activation. Importantly, our results
      indicate that overexpression of SP1 inhibits EPCR promoter activity. Our study
      suggests that EPCR-APC may be a potential therapeutic target for endothelial
      dysfunction in PD. 

PMID- 25061052
TI  - Detection, prevention, and pre-clinical treatment of Alzheimer's disease.

PMID- 25061053
TI  - Distinct chronology of neuronal cell cycle re-entry and tau pathology in the 3xTg
      AD mouse model and Alzheimer's disease patients.
AB  - Cell cycle re-entry in Alzheimer's disease (AD) has emerged as an important
      pathological mechanism in the progression of the disease. This appearance of cell
      cycle related proteins has been linked to tau pathology in AD, but the causal and
      temporal relationship between the two is not completely clear. In this study, we
      found that hyperphosphorylated retinoblastoma protein (ppRb), a key regulator for
      G1/S transition, is correlated with a late marker for hyperphosphorylation of tau
      but not with other early markers for tau alteration in the 3xTg-AD mouse model.
      However, in AD brains, ppRb can colocalize with both early and later markers for
      tau alterations, and can often be found singly in many degenerating neurons,
      indicating the distinct development of pathology between the 3xTg-AD mouse model
      and human AD patients. The conclusions of this study are two-fold. First, our
      findings clearly demonstrate the pathological link between the aberrant cell
      cycle re-entry and tau pathology. Second, the chronological pattern of cell cycle
      re-entry with tau pathology in the 3xTg-AD mouse is different compared to AD
      patients suggesting the distinct pathogenic mechanism between the animal AD model
      and human AD patients. 

PMID- 25061054
TI  - Inclusion of an informant yields strong associations between cognitive complaint
      and longitudinal cognitive outcomes in non-demented elders.
AB  - BACKGROUND: The relation between the source of cognitive complaint and objective
      cognitive performance is not well understood. OBJECTIVE: Examine self and
      informant cognitive complaint as predictors of objective cognitive and functional
      trajectory in non-demented elders. METHODS: Participants from the National
      Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC;
      n = 6133, 72+/-8 years, 68% female) or mild cognitive impairment (MCI; n = 3010,
      74+/-8 years, 55% female). Four independent groups defined cognitive complaint:
      no complaint, self-only complaint, informant-only complaint, or mutual complaint
      (both self and informant complaint). Linear mixed model regression analyses
      related complaint status (referent was no complaint) to cognitive and functional
      trajectories, adjusting for age, sex, race, education, and follow-up period.
      RESULTS: Among NC participants, mutual complaint related to faster decline in
      global cognition (p < 0.0001), language (all p-values <0.0001), processing speed
      (p = 0.0002), and executive functioning (p = 0.0006). Informant-only complaint
      related to faster decline in global cognition (p = 0.0001) and processing speed
      (p = 0.0001). Self-only complaint related to greater decline in immediate (p <
      0.0001) and delayed (p = 0.0005) episodic memory. In MCI, mutual complaint
      related to faster decline in global cognition (p < 0.0001), verbal episodic
      memory (all p-values <0.0001), language (all p-values <0.0001), and processing
      speed(all p-values <0.0006). Informant-only or self-only complaint associations
      with cognitive trajectory did not survive correction factor for multiple
      comparisons.Conclusion: Cognitive complaint appears to have clinical
      significance, as it is related to declines in objective cognitive performance
      over time. Mutual complaint was associated with the worst cognitive trajectory in
      both NC and MCI elders, highlighting the importance of incorporating an informant
      into evaluation of elders whenever feasible.

PMID- 25061055
TI  - Active invasion of Porphyromonas gingivalis and infection-induced complement
      activation in ApoE-/- mice brains.
AB  - Periodontal disease is a polymicrobial inflammatory disease that leads to chronic
      systemic inflammation and direct infiltration of bacteria/bacterial components,
      which may contribute to the development of Alzheimer's disease. ApoE-/- mice were
      orally infected (n = 12) with Porphyromonas gingivalis, Treponema denticola,
      Tannerella forsythia, and Fusobacterium nucleatum as mono- and polymicrobial
      infections. ApoE-/- mice were sacrificed following 12 and 24 weeks of chronic
      infection. Bacterial genomic DNA was isolated from all brain tissues except for
      the F. nucleatum mono-infected group. Polymerase chain reaction was performed
      using universal 16 s rDNA primers and species-specific primer sets for each
      organism to determine whether the infecting pathogens accessed the brain.
      Sequencing amplification products confirmed the invasion of bacteria into the
      brain during infection. The innate immune responses were detected using
      antibodies against complement activation products of C3 convertase stage and the
      membrane attack complex. Molecular methods demonstrated that 6 out of 12 ApoE-/-
      mice brains contained P. gingivalis genomic DNA at 12 weeks (p = 0.006), and 9
      out of 12 at 24 weeks of infection (p = 0.0001). Microglia in both infected and
      control groups demonstrated strong intracellular labeling with C3 and C9, due to
      on-going biosynthesis. The pyramidal neurons of the hippocampus in 4 out of 12
      infected mice brains demonstrated characteristic opsonization with C3 activation
      fragments (p = 0.032). These results show that the oral pathogen P. gingivalis
      was able to access the ApoE-/- mice brain and thereby contributed to complement
      activation with bystander neuronal injury. 

PMID- 25061056
TI  - A therapeutic approach for senile dementias: neuroangiogenesis.
AB  - Alzheimer's disease (AD) and related senile dementias (SDs) represent a growing
      medical and economic crisis in this country. Apart from cautioning persons about
      risk factors, no practical, effective therapy is currently available. Much of the
      recent research in AD has been based on the amyloid cascade theory. Another
      approach assumes a vascular basis for SDs. This paper presents evidence from a
      score of studies that cerebral capillary density (CCD) declines during old age in
      animals and people as well as in AD. Neuroangiogenic (NAG) factors initiate and
      maintain capillaries in the brain. Thus a waning level of these factors and the
      ensuing declining CCD would lead to local areas of reduced oxygen and glucose and
      result in impaired synaptic and neuronal function. The NAG hypothesis developed
      here proposes that the age-linked decline in CCD is a terminal condition in SDs,
      including many cases of AD. This age-linked decline is independent of any other
      of the various pathologies proposed as causing AD and listed in Table 1. Waning
      NAG factors would render the SDs a deficiency condition, somewhat like falling
      androgen levels in aging males. A logical corollary of this hypothesis is that
      chronic replacement therapy with recombinant forms of NAG factors may arrest the
      age-linked decline in CCD and prevent further loss of memory and mental
      deterioration. A transnasal route of therapy seems the most practical one for
      general use in the large aging populations. 

PMID- 25061057
TI  - Chronic brain hypoperfusion due to multi-vessel extracranial atherosclerotic
      disease: a potentially reversible cause of cognitive impairment.
AB  - A 62-year-old patient presented with persistent cognitive deficits 3 months after
      a right temporal ischemic stroke due to ipsilateral carotid occlusion. Work-up
      disclosed hemodynamically significant contralateral carotid artery stenosis and
      left subclavian steal phenomenon. Brain SPECT imaging revealed bihemispheric
      chronic brain hypoperfusion that substantially improved on repeat imaging when
      the subclavian steal was temporarily diminished by inflating a cuff around the
      left arm. Carotid endarterectomy of the asymptomatic carotid stenosis
      substantially ameliorated bihemispheric brain perfusion and reversed cognitive
      impairment. This case highlights that multi-vessel, extracranial atherosclerotic
      disease may cause chronic diffuse brain hypoperfusion that can be associated with
      cognitive impairment. 

PMID- 25061058
TI  - Cognitive enhancers (Nootropics). Part 3: drugs interacting with targets other
      than receptors or enzymes. Disease-modifying drugs. Update 2014.
AB  - Scientists working in the field of Alzheimer's disease and, in particular,
      cognitive enhancers, are very productive. The review "Drugs interacting with
      Targets other than Receptors or Enzymes. Disease-modifying Drugs" was accepted in
      October 2012. In the last 20 months, new targets for the potential treatment of
      Alzheimer's disease were identified. Enormous progress was realized in the
      pharmacological characterization of natural products with cognitive enhancing
      properties. This review covers the evolution of research in this field through
      May 2014. 

PMID- 25061059
TI  - In a rush to decide: deep brain stimulation and dopamine agonist therapy in
      Parkinson's disease.
AB  - BACKGROUND: It has been suggested that all patients with Parkinson's disease (PD)
      who undergo functional neurosurgery have difficulties in slowing down in high
      conflict tasks. However, it is unclear whether concomitant dopaminergic
      medication is responsible for this impairment. OBJECTIVE: To assess perceptual
      decision making in PD patients with bilateral deep brain stimulation. METHODS: We
      tested 27 PD patients with bilateral deep brain stimulation on a task in which
      participants had to filter task relevant information from background noise.
      Thirteen patients were treated with Levodopa monotherapy and 14 patients were
      treated with Levodopa in combination with a dopamine agonist. RESULTS were
      compared to healthy matched controls. RESULTS: We found that all PD patients who
      were treated with a dopamine agonist made faster decisions than controls and PD
      patients who were not exposed to a dopamine agonist. Further, all patients made
      more errors than controls, but there was no difference between the two patient
      groups. CONCLUSIONS: Our results suggest that dopamine agonist therapy rather
      than deep brain stimulation is likely responsible for the inability to slow down
      in high conflict situations in PD. These results further strengthen the need to
      reduce dopamine agonists in PD patients undergoing functional neurosurgery in
      order to prevent them making inadvisable decisions.

PMID- 25061060
TI  - Genetic susceptibility model of Parkinson's disease resulting from exposure of DJ
      1 deficient mice to MPTP: evaluation of neuroprotection by Ubisol-Q10.
AB  - INTRODUCTION: Parkinson's disease arises from a combination of environmental and
      genetic risk factors. At present neither the curative nor preventative therapies
      are available; hence, there is an urgent need to develop reliable animal models
      to facilitate their development. Water soluble nanomiceller formulation of CoQ10
      (Ubisol-Q10) has shown neuroprotection against neurotoxin on human neuronal
      cells. We have combined the genetic deficiency of DJ-1/PARK7 mice with MPTP
      exposure and develop a genetic susceptibility model of PD and evaluated the
      neuroprotective efficacy of (Ubisol-Q10). METHODS: Transgenic mice with DJ-1
      deficiency (DJ-1/PARK7) were given either water or Ubisol-Q10 prophylactically at
      a dose of 6 mg/kg/day added directly to a drinking water for one month followed
      challenged with MPTP injections while keeping the same drinking water regiments.
      Four weeks after the last injection we evaluated neuroprotective efficacy of
      Ubisol-Q10 in DJ-1/MPTP model of PD using histochemical and behavioral readouts.
      RESULTS: We confirmed genetic susceptibility to MPTP and showed that prophylactic
      oral treatment with Ubisol-Q10 significantly offset the neurotoxicity and
      ameliorated motor dysfunction, otherwise correlated with the MPTP injury.
      CONCLUSION: Ubisol-Q10 protects against MPTP-induced neurodegeneration and motor
      dysfunction in DJ-1 deficient mice. Ubisol-Q10 might be a treatment prospect for
      people genetically predisposed to PD as well as with sporadic PD.

PMID- 25061062
TI  - Single versus repetitive injection of lignocaine in the management of carpal
      tunnel syndrome--a randomized controlled trial.
AB  - The aim of this study was to determine the efficacy of single versus repetitive
      injection of lignocaine into the carpal tunnel for the management of carpal
      tunnel syndrome. The 42 patients included were randomly assigned to two Groups:
      group 1 was injected with 4 mL of 1% lignocaine once and Group 2 was injected
      with 4 mL of 1% lignocaine twice a week for 2 weeks. Clinical and
      electrophysiological evaluations were performed at the study onset, and at 6 and
      12 weeks following the final injection. Initially, the groups were similar with
      respect to clinical and electrophysiological findings. All parameters in Group 2
      improved 6 weeks post treatment (p < 0.05), and these improvements persisted at
      12 weeks post treatment (p < 0.05). Repetitive local lignocaine injection was
      effective in reducing the symptoms of carpal tunnel syndrome and improving
      electrophysiological findings. 

PMID- 25061061
TI  - Peripheral administration of the selective inhibitor of soluble tumor necrosis
      factor (TNF) XPro(r)1595 attenuates nigral cell loss and glial activation in 6
      OHDA hemiparkinsonian rats.
AB  - BACKGROUND: Parkinson's disease (PD) is a complex multi-system age-related
      neurodegenerative disorder. Targeting the ongoing neuroinflammation in PD
      patients is one strategy postulated to slow down or halt disease progression.
      Proof-of-concept studies from our group demonstrated that selective inhibition of
      soluble Tumor Necrosis Factor (solTNF) by intranigral delivery of dominant
      negative TNF (DN-TNF) inhibitors reduced neuroinflammation and nigral dopamine
      (DA) neuron loss in endotoxin and neurotoxin rat models of nigral degeneration.
      OBJECTIVE: As a next step toward human clinical trials, we aimed to determine the
      extent to which peripherally administered DN-TNF inhibitor XPro(r)1595 could: i)
      cross the blood-brain-barrier in therapeutically relevant concentrations, ii)
      attenuate neuroinflammation (microglia and astrocyte), and iii) mitigate loss of
      nigral DA neurons in rats receiving a unilateral 6-hydroxydopamine (6-OHDA)
      striatal lesion. METHODS: Rats received unilateral 6-OHDA (20 MUg into the right
      striatum). Three or 14 days after lesion, rats were dosed with XPro(r)1595 (10
      mg/kg in saline, subcutaneous) every third day for 35 days. Forelimb asymmetry
      was used to assess motor deficits after the lesion; brains were harvested 35 days
      after the lesion for analysis of XPro(r)1595 levels, glial activation and nigral
      DA neuron number. RESULTS: Peripheral subcutaneous dosing of XPro(r)1595 achieved
      plasma levels of 1-8 microgram/mL and CSF levels of 1-6 ng/mL depending on the
      time the rats were killed after final XPro(r)1595 injection. Irrespective of
      start date, XPro(r)1595 significantly reduced microglia and astrocyte number in
      SNpc whereas loss of nigral DA neurons was attenuated when drug was started 3,
      but not 14 days after the 6-OHDA lesion. CONCLUSIONS: Our data suggest that
      systemically administered XPro(r)1595 may have disease-modifying potential in PD
      patients where inflammation is part of their pathology.

PMID- 25061063
TI  - Comparison of Dexmedetomidine Versus Propofol on Hospital Costs and Length of
      Stay.
AB  - OBJECTIVE: The objective of this evaluation was to compare total hospital costs
      and length of stay of critically ill patients who received dexmedetomidine versus
      propofol for sedation in the intensive care unit (ICU). METHODS: This was a
      retrospective quality improvement evaluation at a tertiary care, academic medical
      center in the United States. Data were retrieved for patients discharged between
      April 2012 and June 2013. Patients were included if they were admitted to the
      ICU, were 18 years of age or older, and received dexmedetomidine or propofol for
      sedation. Multivariate regression models were developed to determine the
      association between sedative type and hospital costs, ICU length of stay, and
      hospital length of stay. RESULTS: The final cohort included 3294 patients. Of
      these, 2685 received propofol and 609 received dexmedetomidine. The median
      hospital cost was US$31 041 (interquartile range [IQR] US$17 963-US$57 826) in
      the propofol group and US$46 716 (IQR US$31 247 to US$85 490) in the
      dexmedetomidine group (P < .001). The median ICU length of stay was 2 days (IQR 1
      6 days) and 4 days (IQR 2-9 days) in the propofol and dexmedetomidine groups,
      respectively (P < .001). Overall, hospital length of stay was 8 days (IQR 4-15
      days) and 9 days (IQR 5-18 days) in the 2 groups, respectively (P < .001). In the
      multivariate analyses, dexmedetomidine use was associated with increased costs,
      ICU length of stay, and hospital length of stay (P < .001 for each outcome).
      CONCLUSIONS: In this academic medical center, dexmedetomidine use was associated
      with higher costs when compared to propofol for sedation in the ICU. Also, use of
      dexmedetomidine was associated with increased lengths of ICU and hospital stay.
      Future prospective trials are needed to confirm these findings.

PMID- 25061064
TI  - Saccharopolyspora halotolerans sp. nov., a halophilic actinomycete isolated from
      a hypersaline lake.
AB  - A novel actinomycete strain, designated TRM 45123(T), was isolated from a
      hypersaline habitat in Xinjiang Province (40 degrees  20' N 90 degrees  49' E),
      north-west China. The isolate was characterized using a polyphasic approach. 16S
      rRNA gene sequence analysis indicated that strain TRM 45123(T) belonged to the
      genus Saccharopolyspora and was closely related to Saccharopolyspora gloriosae
      (96.7% similarity). The G+C content of the DNA was 69.07 mol%. The isolate
      contained meso-diaminopimelic acid as the diagnostic diamino acid, and arabinose
      and ribose as the major whole-cell sugars. The diagnostic phospholipids were
      phosphatidylethanolamine, phosphatidylcholine and phosphatidylglycerol. The
      predominant menaquinone was MK-9(H4). The major fatty acids were iso-C16 : 0,
      anteiso-C17:0, iso-C15:0 and anteiso-C15:0. On the basis of the evidence from
      this polyphasic study, a novel species, Saccharopolyspora halotolerans sp. nov.,
      is proposed. The type strain of Saccharopolyspora halotolerans is TRM 45123(T) (
      = CCTCC AA 2013006(T) = DSM 45990(T)).

PMID- 25061065
TI  - Description of Propionispira arcuata sp. nov., isolated from a methanogenic
      reactor of cattle waste, reclassification of Zymophilus raffinosivorans and
      Zymophilus paucivorans as Propionispira raffinosivorans comb. nov. and
      Propionispira paucivorans comb. nov. and emended description of the genus
      Propionispira.
AB  - A strictly anaerobic bacterial strain, WK011(T), was isolated from a methanogenic
      reactor treating waste from cattle farms. The cells stained Gram-negative and
      were curved rods with a polar or subpolar flagellum. Spore formation was not
      observed. The optimum temperature for growth was 35  degrees C and the optimum pH
      was 6.7. Tests for oxidase, catalase and nitrate-reduction activities were
      negative. Hydrogen sulfide was produced. The strain fermented carbohydrates and
      produced acetate and propionate as major fermentation products. The genomic DNA
      G+C content was 41.7 mol%. The major cellular fatty acids were C15:0,
      C16:1omega9c and C18:1 dimethylacetal. The diagnostic diamino acid of the cell
      wall peptidoglycan was meso-diaminopimelic acid. The most closely related species
      to strain WK011(T) on the basis of 16S rRNA gene sequences were Propionispira
      arboris and Zymophilus raffinosivorans (95.6% sequence similarity to the type
      strains of both species). It was shown by phylogenetic and phenotypic examination
      of the type strains of related species, including the second species of the genus
      Zymophilus, Zymophilus paucivorans, that the two genera should be combined and
      that the two species of the genus Zymophilus should be transferred to the genus
      Propionispira, as Propionispira raffinosivorans comb. nov. (type strain SH2(T) =
      ATCC 49691(T) = DSM 20765(T)) and Propionispira paucivorans comb. nov. (type
      strain AA1(T) = ATCC 49689(T) = DSM 20756(T)), with an emended description of the
      genus Propionispira. Based on differences in the phylogenetic and phenotypic
      characteristics of strain WK011(T) from those of closely related species, the
      novel species Propionispira arcuata sp. nov. is proposed to accommodate the
      strain. The type strain is WK011(T) ( = JCM 16475(T) = DSM 22929(T)).

PMID- 25061066
TI  - Alcanivorax xenomutans sp. nov., a hydrocarbonoclastic bacterium isolated from a
      shrimp cultivation pond.
AB  - Two bacterial strains (JC109(T) and JC261) were isolated from a sediment sample
      collected from a shrimp cultivation pond in Tamil Nadu (India). Cells were Gram
      stain-negative, motile rods. Both strains were positive for catalase and oxidase,
      hydrolysed Tween 80, and grew chemo-organoheterotrophically with an optimal pH of
      6 (range pH 4-9) and at 30  degrees C (range 25-40  degrees C). Based on 16S rRNA
      gene sequence analysis, strains JC109(T) and JC261 were identified as belonging
      to the genus Alcanivorax with Alcanivorax dieselolei B-5(T) (sequence similarity
      values of 99.3 and 99.7%, respectively) and Alcanivorax balearicus MACL04(T)
      (sequence similarity values of 98.8 and 99.2%, respectively) as their closest
      phylogenetic neighbours. The 16S rRNA gene sequence similarity between strains
      JC109(T) and JC261 was 99.6%. The level of DNA-DNA relatedness between the two
      strains was 88%. Strain JC109(T) showed 31 +/- 1 and 26 +/- 2% DNA-DNA
      relatedness with A. dieselolei DSM 16502(T) and A. balearicus DSM 23776(T),
      respectively. The DNA G+C content of strains JC109(T) and JC261 was 54.5 and 53.4
      mol%, respectively. Polar lipids of strain JC109(T) included
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two
      unidentified aminophospholipids, two unidentified phospholipids and two
      unidentified lipids. The major fatty acids were C10:0, C12:0, C16:0, C12:0 3-OH,
      C16:1omega7c, C18:1omega7c and C19:0 cyclo omega8c. Both strains could utilize
      diesel oil and a variety of xenobiotics as carbon and energy sources. The results
      of physiological, biochemical, chemotaxonomic and molecular analyses allowed the
      clear differentiation of strains JC109(T) and JC261 from all other members of the
      genus Alcanivorax. Strains JC109(T) and JC261 are thus considered to represent a
      novel species, for which the name Alcanivorax xenomutans sp. nov. is proposed.
      The type strain is JC109(T) ( = KCTC 23751(T) = NBRC 108843(T)).

PMID- 25061067
TI  - Predicting protein phosphorylation from gene expression: top methods from the
      IMPROVER Species Translation Challenge.
AB  - MOTIVATION: Using gene expression to infer changes in protein phosphorylation
      levels induced in cells by various stimuli is an outstanding problem. The intra
      species protein phosphorylation challenge organized by the IMPROVER consortium
      provided the framework to identify the best approaches to address this issue.
      RESULTS: Rat lung epithelial cells were treated with 52 stimuli, and gene
      expression and phosphorylation levels were measured. Competing teams used gene
      expression data from 26 stimuli to develop protein phosphorylation prediction
      models and were ranked based on prediction performance for the remaining 26
      stimuli. Three teams were tied in first place in this challenge achieving a
      balanced accuracy of about 70%, indicating that gene expression is only
      moderately predictive of protein phosphorylation. In spite of the similar
      performance, the approaches used by these three teams, described in detail in
      this article, were different, with the average number of predictor genes per
      phosphoprotein used by the teams ranging from 3 to 124. However, a significant
      overlap of gene signatures between teams was observed for the majority of the
      proteins considered, while Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathways were enriched in the union of the predictor genes of the three teams for
      multiple proteins. AVAILABILITY AND IMPLEMENTATION: Gene expression and protein
      phosphorylation data are available from ArrayExpress (E-MTAB-2091). Software
      implementation of the approach of Teams 49 and 75 are available at
      http://bioinformaticsprb.med.wayne.edu and
      http://people.cs.clemson.edu/~luofeng/sbv.rar, respectively. CONTACT:
      gyanbhanot@gmail.com or luofeng@clemson.edu or atarca@med.wayne.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25061068
TI  - Mas-o-menos: a simple sign averaging method for discrimination in genomic data
      analysis.
AB  - MOTIVATION: The successful translation of genomic signatures into clinical
      settings relies on good discrimination between patient subgroups. Many
      sophisticated algorithms have been proposed in the statistics and machine
      learning literature, but in practice simpler algorithms are often used. However,
      few simple algorithms have been formally described or systematically
      investigated. RESULTS: We give a precise definition of a popular simple method we
      refer to as mas-o-menos, which calculates prognostic scores for discrimination by
      summing standardized predictors, weighted by the signs of their marginal
      associations with the outcome. We study its behavior theoretically, in
      simulations and in an extensive analysis of 27 independent gene expression
      studies of bladder, breast and ovarian cancer, altogether totaling 3833 patients
      with survival outcomes. We find that despite its simplicity, mas-o-menos can
      achieve good discrimination performance. It performs no worse, and sometimes
      better, than popular and much more CPU-intensive methods for discrimination,
      including lasso and ridge regression. AVAILABILITY AND IMPLEMENTATION: Mas-o
      menos is implemented for survival analysis as an option in the survHD package,
      available from http://www.bitbucket.org/lwaldron/survhd and submitted to
      Bioconductor.

PMID- 25061070
TI  - STAMP: statistical analysis of taxonomic and functional profiles.
AB  - STAMP is a graphical software package that provides statistical hypothesis tests
      and exploratory plots for analysing taxonomic and functional profiles. It
      supports tests for comparing pairs of samples or samples organized into two or
      more treatment groups. Effect sizes and confidence intervals are provided to
      allow critical assessment of the biological relevancy of test results. A user
      friendly graphical interface permits easy exploration of statistical results and
      generation of publication-quality plots. AVAILABILITY AND IMPLEMENTATION: STAMP
      is licensed under the GNU GPL. Python source code and binaries are available from
      our website at: http://kiwi.cs.dal.ca/Software/STAMP.

PMID- 25061069
TI  - Inferring condition-specific miRNA activity from matched miRNA and mRNA
      expression data.
AB  - MOTIVATION: MicroRNAs (miRNAs) play crucial roles in complex cellular networks by
      binding to the messenger RNAs (mRNAs) of protein coding genes. It has been found
      that miRNA regulation is often condition-specific. A number of computational
      approaches have been developed to identify miRNA activity specific to a condition
      of interest using gene expression data. However, most of the methods only use the
      data in a single condition, and thus, the activity discovered may not be unique
      to the condition of interest. Additionally, these methods are based on
      statistical associations between the gene expression levels of miRNAs and mRNAs,
      so they may not be able to reveal real gene regulatory relationships, which are
      causal relationships. RESULTS: We propose a novel method to infer condition
      specific miRNA activity by considering (i) the difference between the regulatory
      behavior that an miRNA has in the condition of interest and its behavior in the
      other conditions; (ii) the causal semantics of miRNA-mRNA relationships. The
      method is applied to the epithelial-mesenchymal transition (EMT) and multi-class
      cancer (MCC) datasets. The validation by the results of transfection experiments
      shows that our approach is effective in discovering significant miRNA-mRNA
      interactions. Functional and pathway analysis and literature validation indicate
      that the identified active miRNAs are closely associated with the specific
      biological processes, diseases and pathways. More detailed analysis of the
      activity of the active miRNAs implies that some active miRNAs show different
      regulation types in different conditions, but some have the same regulation types
      and their activity only differs in different conditions in the strengths of
      regulation. AVAILABILITY AND IMPLEMENTATION: The R and Matlab scripts are in the
      Supplementary materials.

PMID- 25061071
TI  - FisHiCal: an R package for iterative FISH-based calibration of Hi-C data.
AB  - The fluorescence in situ hybridization (FISH) method has been providing valuable
      information on physical distances between loci (via image analysis) for several
      decades. Recently, high-throughput data on nearby chemical contacts between and
      within chromosomes became available with the Hi-C method. Here, we present
      FisHiCal, an R package for an iterative FISH-based Hi-C calibration that exploits
      in full the information coming from these methods. We describe here our
      calibration model and present 3D inference methods that we have developed for
      increasing its usability, namely, 3D reconstruction through local stress
      minimization and detection of spatial inconsistencies. We next confirm our
      calibration across three human cell lines and explain how the output of our
      methods could inform our model, defining an iterative calibration pipeline, with
      applications for quality assessment and meta-analysis. AVAILABILITY AND
      IMPLEMENTATION: FisHiCal v1.1 is available from http://cran.r-project.org/.

PMID- 25061072
TI  - Systematic analysis of gene properties influencing organ system phenotypes in
      mammalian perturbations.
AB  - MOTIVATION: Diseases and adverse drug reactions are frequently caused by
      disruptions in gene functionality. Gaining insight into the global system
      properties governing the relationships between genotype and phenotype is thus
      crucial to understand and interfere with perturbations in complex organisms such
      as diseases states. RESULTS: We present a systematic analysis of phenotypic
      information of 5047 perturbations of single genes in mice, 4766 human diseases
      and 1666 drugs that examines the relationships between different gene properties
      and the phenotypic impact at the organ system level in mammalian organisms. We
      observe that while single gene perturbations and alterations of nonessential,
      tissue-specific genes or those with low betweenness centrality in protein-protein
      interaction networks often show organ-specific effects, multiple gene alterations
      resulting e.g. from complex disorders and drug treatments have a more widespread
      impact. Interestingly, certain cellular localizations are distinctly associated
      to systemic effects in monogenic disease genes and mouse gene perturbations, such
      as the lumen of intracellular organelles and transcription factor complexes,
      respectively. In summary, we show that the broadness of the phenotypic effect is
      clearly related to certain gene properties and is an indicator of the severity of
      perturbations. This work contributes to the understanding of gene properties
      influencing the systemic effects of diseases and drugs.

PMID- 25061073
TI  - Observing the use of tactile schedules.
AB  - This article explores the use of tactile schedules in a heterogeneous sample of
      children with congenital blindness and varying degrees of additional
      disabilities. Basic conditions for the use of tactile schedules are proposed and
      discussed. Child behaviour indicative of some particular functions that can be
      attained with the use of tactile schedules, such as sense of agency and increased
      predictability and communication, is described and discussed. The role of the
      teacher is emphasized throughout the article.

PMID- 25061074
TI  - Vision 2020: moving beyond blindness.
AB  - Most industrialized countries and many emerging economies have chosen to define
      'blindness' at a visual acuity above that which WHO uses. This reflects the
      increasing visual demands of modern society for tasks such as driving or using
      cell phones. Meeting these demands will require more highly skilled health
      workers using more sophisticated equipment than has generally been considered
      sufficient for primary eye care. 

PMID- 25061075
TI  - Educating the security forces, a high risk group in malaria elimination efforts:
      an example from Sri Lanka.
AB  - BACKGROUND: The security forces are a high risk group for malaria transmission in
      Sri Lanka. Interrupting transmission and maintaining surveillance in this group
      is an important component of elimination efforts. The objective of the study was
      to develop a prototype educational programme on malaria for security forces
      serving in endemic areas. METHODS: An interactive seminar was designed to deliver
      the required knowledge. The content was on current status, transmission, signs
      and symptoms and the role of security personnel in identification and prevention
      of malaria. Each seminar was preceded by a pre-test and followed by a post test
      to assess the improvement of knowledge. RESULTS: Fifty seminars were held in
      eight districts over 2 months with 2301 security forces personnel participating.
      Pre seminar knowledge on malaria was significantly better in the medical corps,
      those who had completed secondary education and in the Army compared to other
      security forces (p<0.001). Participation in the seminar resulted in an
      improvement in all domains tested as shown by test scores in post seminar
      assessment (p<0.001). CONCLUSIONS: Conducting a formal educational programme is
      an effective strategy to improve awareness on malaria amongst security forces
      personnel who are a high risk group for re-introduction of malaria into the
      country.

PMID- 25061076
TI  - Long-term mortality after first-ever and recurrent stroke in young adults.
AB  - BACKGROUND AND PURPOSE: Mortality after first-ever stroke, and particularly after
      recurrent stroke, and predictors of long-term mortality among young and middle
      aged stroke patients are not well-known. We assessed 17-year risk of mortality
      with focus on the effect of recurrence on the risk of death of young and middle
      aged patients with stroke. METHODS: Mortality and recurrent stroke rate of 970
      consecutive 30-day survivors of first-ever ischemic stroke aged 15 to 49 years
      (1994-2007) were studied. Prospective follow-up data came from the Finnish Care
      Register for Health Care and Statistics Finland. Mean follow-up was 10.2+/-4.3
      years. We compared survival between clinical subgroups and identified factors
      associated with mortality. Standardized mortality ratio was calculated for
      demographic and pathogenetic subgroups using mortality data of the general
      population matched with age, sex, calendar year, and geographical area. RESULTS:
      At the end of follow-up, 152 (15.7%) patients had died (cumulative risk, 23.0%;
      95% confidence interval, 19.1%-26.9%) and 132 (13.6%) had experienced a recurrent
      stroke. After adjusting for baseline characteristics, recurrent stroke was
      statistically the most important risk factor for mortality after first-ever
      ischemic stroke (hazard ratio, 16.68; 95% confidence interval, 2.33-119.56;
      P=0.005). Observed mortality was 7-fold higher than the expected mortality
      (standardized mortality ratio, 6.94; 95% confidence interval, 5.84-8.04) and
      particularly high among patients who experienced a recurrent stroke (standardized
      mortality ratio, 14.43; 95% confidence interval, 10.11-18.74). CONCLUSIONS: The
      high mortality rates and the striking impact of recurrent stroke on the risk of
      death should lead to development of more robust primary and secondary prevention
      strategies for young patients with stroke.

PMID- 25061077
TI  - Modeling immunity and inflammation in stroke: can mice be trusted?

PMID- 25061078
TI  - Different risk factor profiles for ischemic and hemorrhagic stroke in type 1
      diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Despite the fact that patients with type 1 diabetes
      mellitus have a markedly increased risk of experiencing a stroke, independent
      risk factors for stroke and its subtypes in these patients have remained unclear.
      METHODS: A total of 4083 patients with type 1 diabetes mellitus from the Finnish
      Diabetic Nephropathy (FinnDiane) Study, without a history of stroke at baseline,
      were included. Strokes were classified based on medical files and brain imaging.
      At baseline, mean age was 37.4+/-11.8 years, duration of diabetes mellitus was
      20.0 (11.0-30.0) years, and 51% were men. During 9.0+/-2.7 years (36 680 patient
      years) of follow-up, 105 patients experienced an ischemic stroke and 44 a
      hemorrhagic stroke. Cox proportional hazards analyses were performed to determine
      independent risk factors. RESULTS: Independent risk factors for ischemic stroke
      were duration of diabetes mellitus, presence of diabetic nephropathy, higher
      hemoglobin A1c, higher systolic blood pressure, insulin resistance, and history
      of smoking, whereas sex, lipids, high-sensitivity C-reactive protein, and the
      metabolic syndrome were not associated with an increased risk. Diabetic
      nephropathy, severe diabetic retinopathy, higher systolic blood pressure, and
      lower body mass index were independently associated with hemorrhagic stroke.
      CONCLUSIONS: The risk factor profile for ischemic stroke seems partly different
      from that of hemorrhagic stroke in patients with type 1 diabetes mellitus.

PMID- 25061079
TI  - Modeling immunity and inflammation in stroke: don't be afraid of mice?

PMID- 25061080
TI  - Intraventricular thrombolysis in intracerebral hemorrhage requiring
      ventriculostomy: a decade-long real-world experience.
AB  - BACKGROUND AND PURPOSE: Intraventricular thrombolysis (IVT) is a promising
      treatment in facilitating intraventricular clot resolution after intraventricular
      hemorrhage. We examined in-hospital outcomes and resource utilization after
      thrombolysis in patients with intraventricular hemorrhage requiring
      ventriculostomy in a real-world setting. METHODS: We identified adult patients
      with primary diagnosis of nontraumatic intracerebral hemorrhage requiring
      ventriculostomy from the Nationwide Inpatient Sample from 2002 to 2011. We
      compared demographic and hospital characteristics, comorbidities, inpatient
      outcomes, and resource utilization measures between patients treated with IVT and
      those managed with ventriculostomy, but without IVT. Population estimates were
      extrapolated using standard Nationwide Inpatient Sample weighting algorithms.
      RESULTS: We included 34 044 patients in the analysis, of whom 1133 (3.3%)
      received IVT. The thrombolysis group had significantly lower inpatient mortality
      (32.4% versus 41.6%; P=0.001) and it remained lower after controlling for
      baseline demographics, hospital characteristics, comorbidity, case severity, and
      withdrawal of care status (adjusted odds ratio, 0.670; 95% confidence interval,
      0.520-0.865; P=0.002). There was a trend toward favorable discharge (home or
      rehabilitation) among the thrombolysis cohort (adjusted odds ratio, 1.335; 95%
      confidence interval, 0.983-1.812; P=0.064). The adjusted rates of bacterial
      meningitis and ventricular shunt placement were similar between groups. The
      thrombolysis group had longer length of stay and higher inflation-adjusted cost
      of care, but cost of care per day length of stay was similar to the non-IVT
      group. CONCLUSIONS: IVT for intracerebral hemorrhage requiring ventriculostomy
      resulted in lower inpatient mortality and a trend toward favorable discharge
      outcome with similar rates of inpatient complications compared with the non-IVT
      group.

PMID- 25061081
TI  - Response to letter regarding article, "blocking of alpha4 integrin does not
      protect from acute ischemic stroke in mice".

PMID- 25061082
TI  - Modeling immunity and inflammation in stroke: differences between rodents and
      humans?

PMID- 25061083
TI  - Letter by Elkins et al regarding article, "blocking of alpha4 integrin does not
      protect from acute ischemic stroke in mice".

PMID- 25061085
TI  - Achieving a climate for patient safety by focusing on relationships.
AB  - OBJECTIVE: Despite many initiatives, advances in patient safety remain uneven in
      part because poor relationships among health professionals have not been
      addressed. The purpose of this study was to determine whether relationships
      between health professionals contributed to a patient safety climate, after
      implementation of an intervention to improve inter-professional collaboration.
      DESIGN/SETTING: This was a secondary analysis of data collected to evaluate the
      Interprofessional Model of Patient Care (IPMPC) at The Ottawa Hospital in
      Ontario, Canada, which consists of five sites. A series of generalized estimating
      equation models were generated, accounting for the clustering of responses by
      site. PARTICIPANTS: Thirteen health professionals including physicians, nurses,
      physiotherapists and others (n = 1896) completed anonymous surveys about 1 year
      after the IPMPC was introduced. INTERVENTION: The IPMPC was implemented to
      improve interdisciplinary collaboration. MAIN OUTCOME MEASURES: Reliable
      instruments were used to measure collaboration, respect, inter-professional
      conflict and patient safety climate. RESULTS: Collaboration (beta = 0.13; P =
      0.002) and respect (beta = 1.07; P = 0.03) were significant independent
      predictors of patient safety climate. Conflict was an independent and significant
      inverse predictor of patient safety climate (beta = -0.29; P = 0.03), but did not
      moderate linkages between collaboration and patient safety climate or between
      respect and patient safety climate. CONCLUSIONS: Through the IPMPC, all health
      professionals learned how to collaborate and build a patient safety climate, even
      in the presence of inter-professional conflict. Efforts by others to foster
      better work relationships may yield similar improvements in patient safety
      climate.

PMID- 25061084
TI  - The globin gene repertoire of lampreys: convergent evolution of hemoglobin and
      myoglobin in jawed and jawless vertebrates.
AB  - Agnathans (jawless vertebrates) occupy a key phylogenetic position for
      illuminating the evolution of vertebrate anatomy and physiology. Evaluation of
      the agnathan globin gene repertoire can thus aid efforts to reconstruct the
      origin and evolution of the globin genes of vertebrates, a superfamily that
      includes the well-known model proteins hemoglobin and myoglobin. Here, we report
      a comprehensive analysis of the genome of the sea lamprey (Petromyzon marinus)
      which revealed 23 intact globin genes and two hemoglobin pseudogenes. Analyses of
      the genome of the Arctic lamprey (Lethenteron camtschaticum) identified 18 full
      length and five partial globin gene sequences. The majority of the globin genes
      in both lamprey species correspond to the known agnathan hemoglobins. Both
      genomes harbor two copies of globin X, an ancient globin gene that has a broad
      phylogenetic distribution in the animal kingdom. Surprisingly, we found no
      evidence for an ortholog of neuroglobin in the lamprey genomes. Expression and
      phylogenetic analyses identified an ortholog of cytoglobin in the lampreys; in
      fact, our results indicate that cytoglobin is the only orthologous vertebrate
      specific globin that has been retained in both gnathostomes and agnathans.
      Notably, we also found two globins that are highly expressed in the heart of P.
      marinus, thus representing functional myoglobins. Both genes have orthologs in L.
      camtschaticum. Phylogenetic analyses indicate that these heart-expressed globins
      are not orthologous to the myoglobins of jawed vertebrates (Gnathostomata), but
      originated independently within the agnathans. The agnathan myoglobin and
      hemoglobin proteins form a monophyletic group to the exclusion of functionally
      analogous myoglobins and hemoglobins of gnathostomes, indicating that specialized
      respiratory proteins for O2 transport in the blood and O2 storage in the striated
      muscles evolved independently in both lineages. This dual convergence of O2
      transport and O2-storage proteins in agnathans and gnathostomes involved the
      convergent co-option of different precursor proteins in the ancestral globin
      repertoire of vertebrates. 

PMID- 25061086
TI  - Relationship of Paternity Status, Welfare Reform Period, and Racial/Ethnic
      Disparities in Infant Mortality.
AB  - The objective of this study was to examine the relationship of paternity status,
      welfare reform period, and racial/ethnic disparities in infant mortality. The
      study used retrospective analysis of birth outcomes data from singleton
      birth/infant death data in Milwaukee, Wisconsin, from 1993 to 2009. Multivariate
      logistic regression was used to examine the relationship between paternity
      status, welfare reform period, and infant mortality, adjusting for maternal and
      infant characteristics. Data consisted of almost 185,000 singleton live births
      and 1,739 infant deaths. Although unmarried women with no father on record made
      up about 32% of the live births, they accounted for over two thirds of the infant
      deaths compared with married women with established paternity who made up 39% of
      live births but had about a quarter of infant deaths. After adjustments, any form
      of paternity establishment was protective against infant mortality across all
      racial/ethnic groups. Unmarried women with no father on record had twice to
      triple the odds of infant mortality among all racial/ethnic groups. The
      likelihood of infant mortality was only significantly greater for African
      American women in the postwelfare (1999-2004; odds ratio = 1.27; 95% confidence
      interval = 1.10-1.46) period compared with the 1993 to 1998 period. Study
      findings suggest that any form of paternity establishment may have protective
      effect against infant mortality. Welfare reform changes may have reduced some of
      the protection against infant mortality among unmarried African American women
      that was present before the welfare legislation. Policies and programs that
      promote or support increased paternal involvement and establishment of paternity
      may improve birth outcomes and help reduce infant mortality. 

PMID- 25061087
TI  - Prostate cancer support groups: Canada-based specialists' perspectives.
AB  - To understand prostate cancer (PCa) specialists' views about prostate cancer
      support groups (PCSGs), a volunteer sample of Canada-based PCa specialists (n =
      150), including urologists (n = 100), radiation oncologists (n = 40), and medical
      oncologists (n = 10) were surveyed. The 56-item questionnaire used in this study
      included six sets of attitudinal items to measure prostate cancer specialists'
      beliefs about positive and negative influences of PCSGs, reasons for attending
      PCSGs, the attributes of effective PCSGs, and the value of face-to-face and web
      based PCSGs. In addition, an open-ended question was included to invite
      additional input from participants. Results showed that PCSGs were positively
      valued, particularly for information sharing, education and psychosocial support.
      Inclusivity, privacy, and accessibility were identified as potential barriers,
      and recommendations were made for better marketing PCSGs to increase engagement.
      Findings suggest prostate cancer specialists highly valued the role and potential
      benefits of face-to-face PCSGs. Information provision and an educational role
      were perceived as key benefits. Some concerns were expressed about the ability of
      web-based PCSGs to effectively engage and educate men who experience prostate
      cancer. 

PMID- 25061088
TI  - Study on alcohol dependence and factors related to erectile dysfunction among
      aborigines in Taiwan.
AB  - Relatively few studies have addressed the risk factors of erectile dysfunction
      (ED) in Taiwanese- most have described ED and medical problems in the general
      population. In this study, the cardiovascular risk factors of ED among aborigines
      in Taiwan were investigated. However, alcohol dependence (AD) was prevalent in
      Taiwan's aborigine population. So this study also focused on the relationship
      among AD, the cardiovascular risk factors and ED. A cross-sectional study was
      conducted, and data was obtained from a baseline survey of 192 aboriginal adults
      (35-75 years of age). The participants' demographic data, AD, markers of
      endothelial function, serum testosterone, and ED status were assessed. Ninety
      four (49%) of the 192 participants had a history of alcoholism and 79 (84%) of
      those with alcoholism had ED. The study reported that AD and hyperlipidemia,
      metabolic syndrome (MetS), ED, abnormality of testosterone, and high-sensitivity
      C-reactive protein are highly prevalent among the aborigines. Factors that may
      affect ED included age, AD, central obesity, diabetes mellitus, hyperlipidemia,
      hypertension, MetS, and testosterone. ED is highly prevalent among aborigines
      with the risk factors of AD, MetS, old age, and abnormal testosterone serum
      level. MetS, atherosclerosis, and ED are risk factors for cardiovascular
      diseases. Hence, an increased focus on Taiwanese aborigines with ED is necessary.

PMID- 25061089
TI  - Current issues in malignant pleural mesothelioma evaluation and management.
AB  - Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated
      with occupational asbestos exposure and is steadily increasing in worldwide
      incidence. Patients typically present at an older age, with advanced clinical
      stage and other medical comorbidities, making management quite challenging.
      Despite great efforts, the prognosis of MPM remains poor, especially at
      progression after initial treatment. Macroscopic complete resection of MPM can be
      achieved through extrapleural pneumonectomy (EPP) or extended (ie, radical)
      pleurectomy (e-P/D) in selected patients and can result in prolonged survival
      when incorporated into a multimodality approach. Given the morbidity associated
      with surgical resection of MPM, optimizing identification of appropriate patients
      is essential. Unfortunately, most patients are not candidates for EPP or e-P/D
      due to advanced stage, age, and/or medical comorbidity. Pemetrexed and platinum
      combination chemotherapy has become the cornerstone of therapy for patients with
      unresectable disease because the combination is associated with improved survival
      and quality of life in treated patients. However, MPM eventually becomes
      resistant to initial therapy, and benefit to further lines of therapy has not
      been substantiated in randomized clinical trials. Translational research has
      provided exciting insights into tumorigenesis, biomarkers, and immune response in
      MPM, leading to the development of multiple novel therapeutic agents that are
      currently in clinical trials. These advances hold the promise of a new era in the
      treatment of MPM and suggest that this disease will not be left behind in the war
      on cancer. 

PMID- 25061090
TI  - Type 2 diabetes mellitus is associated with increased mortality in Chinese
      patients receiving curative surgery for colon cancer.
AB  - BACKGROUND: We investigated the association between diabetes mellitus (DM) and
      the prognosis of patients with early colon cancer who had undergone curative
      surgery. METHODS: From three national databases of patients in Taiwan, we
      selected a cohort of colon cancer patients who had been newly diagnosed with
      stage I or stage II colon cancer between January 1, 2004 and December 31, 2008
      and had undergone curative surgery. We collected information regarding DM (type 2
      DM only), the use of antidiabetic medications, other comorbidities, and survival
      outcomes. The colon cancer-specific survival (CSS) and the overall survival (OS)
      were compared between patients with and without DM. RESULTS: We selected 6,937
      colon cancer patients, among whom 1,371 (19.8%) had DM. The colon cancer patients
      with DM were older and less likely to receive adjuvant chemotherapy but had a
      similar tumor stage and grade, compared with colon cancer patients without DM.
      Compared with colon cancer patients without DM, patients with DM had
      significantly shorter OS (5-year OS: 71.0% vs. 81.7%) and CSS (5-year CSS: 86.7%
      vs. 89.2%). After adjusting for age, sex, stage, adjuvant chemotherapy, and
      comorbidities in our multivariate analysis, DM remained an independent prognostic
      factor for overall mortality (adjusted hazards ratio: 1.32, 95% confidence
      interval: 1.18-1.49), but not for cancer-specific mortality. Among the colon
      cancer patients who had received antidiabetic drug therapy, patients who had used
      insulin had significantly shorter CSS and OS than patients who had not.
      CONCLUSION: Among patients who receive curative surgery for early colon cancer,
      DM is a predictor of increased overall mortality.

PMID- 25061092
TI  - Transition Planning for Youth With Special Health Care Needs (YSHCN) in Illinois
      Schools.
AB  - "Transition Planning for Youth with Special Health Care Needs (YSHCN)" chronicles
      the research and work completed by agencies in Illinois to provide examples of
      best practice in transition planning. Increasing numbers of YSHCN survive into
      adulthood creating a need for focus on the transition to adult life for these
      young people, including meeting health care needs. As a part of the Transitions
      project, the Illinois Chapter of the American Academy of Pediatrics and the
      University of Illinois at Chicago Division of Specialized Care for Children
      surveyed Illinois public high schools to identify transition planning efforts,
      staff training needs and used those results to develop and implement training. A
      natural way to organize health services is by integration with school transition
      services. The credentialed school nurse would be the ideal person to contribute
      to the development of the health care transition plans based on the student's
      heath care provider's medical management plan. 

PMID- 25061091
TI  - Pre-exercise participation cardiovascular screening in a heterogeneous cohort of
      adult cancer patients.
AB  - BACKGROUND: The purpose of this study was to investigate the extent of pre
      exercise participation ("preparticipation") health screening in a heterogeneous
      cohort of adult cancer patients. METHODS: Patients (n = 413) with histologically
      confirmed solid or hematologic malignancy were categorized into preparticipation
      health screening risk stratification based on American College Sports Medicine
      (ACSM) recommendations. Risk of an exercise-related event was evaluated during a
      symptom-limited cardiopulmonary exercise test (CPET) with 12-lead
      electrocardiography (ECG). RESULTS: Participant risk was categorized as low risk
      (n = 59, 14%), moderate risk (n = 217, 53%), and high risk (n = 137, 33%). Mean
      peak oxygen consumption was 21.7 +/- 6.7 mL/kg(-1) per minute(-1) or 19.5 +/-
      21.7% below age- and sex-predicted sedentary values. No major serious adverse
      events or fatal events were observed during CPET procedures. A total of 31
      positive ECG tests were observed, for an event rate of 8%. ACSM risk
      stratification did not predict the risk of a positive test. Age, statin use,
      antiplatelet therapy use, cardiovascular disease, prior treatment with
      anthracycline or radiation therapy, and being sedentary were predictors of a
      positive test (all p < .10). CONCLUSION: The patient risk-stratification profile
      strongly suggests that the use of formalized preparticipation health screening is
      required in all oncology scenarios; however, risk of an exercise-induced event is
      low, suggesting that the use of exercise testing is not required for pre-exercise
      clearance in the majority of patients.

PMID- 25061093
TI  - Challenges of Documenting Schoolchildren's Psychosocial Health: A Qualitative
      Study.
AB  - The aim of this study was to explore school nurses' experience of challenges
      related to documenting schoolchildren's psychosocial health in Sweden. Six focus
      group discussions were carried out. Areas for discussions included questions
      about situations, especially challenging to document as well as what constrains
      and/or facilitates documenting psychosocial health problem issues. Qualitative
      content analysis was used for interpreting the data. The analysis resulted in one
      overarching theme: having to do one's duty and being afraid of doing wrong; and
      three subthemes: uncertainty related to one's own ability, concerns related to
      future consequences, and strategies to handle the documentation. School nurses
      relying on their intuition and using a structured documentation model may
      increase the opportunities for a reliable documentation. To further develop their
      professional skills with regular, clinical supervision can be of great
      importance. This in turn may increase contributions to research and development
      for the benefit of schoolchildren's psychosocial health. 

PMID- 25061094
TI  - Role of cytoskeleton in regulating fusion of nucleoli: a study using the
      activated mouse oocyte model.
AB  - Although fusion of nucleoli was observed during pronuclear development of zygotes
      and the behavior of nucleoli in pronuclei has been suggested as an indicator of
      embryonic developmental potential, the mechanism for nucleolar fusion is unclear.
      Although both cytoskeleton and the nucleolus are important cellular entities,
      there are no special reports on the relationship between the two. Role of
      cytoskeleton in regulating fusion of nucleoli was studied using the activated
      mouse oocyte model. Mouse oocytes were cultured for 6 h in activating medium
      (Ca2+-free CZB medium containing 10 mM SrCl2) supplemented with or without
      inhibitors for cytoskeleton or protein synthesis before pronuclear formation,
      nucleolar fusion, and the activity of maturation-promoting factor (MPF) were
      examined. Whereas treatment with microfilament inhibitor cytochalasin D or B or
      intermediate filament inhibitor acrylamide suppressed nucleolar fusion
      efficiently, treatment with microtubule inhibitor demecolcine or nocodazole or
      protein synthesis inhibitor cycloheximide had no effect. The cytochalasin D- or
      acrylamide-sensitive temporal window coincided well with the reported temporal
      window for nucleolar fusion in activated oocytes. Whereas a continuous incubation
      with demecolcine prevented pronuclear formation, pronuclei formed normally when
      demecolcine was excluded during the first hour of activation treatment when the
      MPF activity dropped dramatically. The results suggest that 1) microfilaments and
      intermediate filaments but not microtubules support nucleolar fusion, 2) proteins
      required for nucleolar fusion including microfilaments and intermediate filaments
      are not de novo synthesized, and 3) microtubule disruption prevents pronuclear
      formation by activating MPF.

PMID- 25061095
TI  - Ovarian steroid hormone-regulated uterine remodeling occurs independently of
      macrophages in mice.
AB  - Macrophages are abundant in the uterine stroma and are intimately juxtaposed with
      other cell lineages comprising the uterine epithelial and stromal compartments.
      We postulated that macrophages may participate in mediating or amplifying the
      effects of ovarian steroid hormones to facilitate the uterine remodeling that is
      a characteristic feature of every estrus cycle and is essential for pregnancy.
      Using the Cd11b-Dtr transgenic mouse model with an ovariectomy and hormone
      replacement strategy, we depleted macrophages to determine their role in hormone
      driven proliferation of uterine epithelial and stromal cells and uterine vascular
      development. Following diphtheria toxin (DT) administration, approximately 85% of
      EMR1-positive (EMR1+) macrophages, as well as 70% of CD11C+ dendritic cells, were
      depleted from Cd11b-Dtr mice. There was no change in bromodeoxyuridine
      incorporation into epithelial cells induced to proliferate by administration of
      17beta-estradiol (E2) to ovariectomized mice or into stromal cells induced to
      proliferate in response to E2 and progesterone (P4), and the resulting sizes and
      structures of the luminal epithelial and stromal cell compartments were not
      altered compared with those of leukocyte replete controls. Depletion of CD11B+
      myeloid cells failed to alter the density or pattern of distribution of uterine
      blood vessels, as identified by staining PECAM1-positive endothelial cells in the
      uterine stroma of E2- or E2 combined with P4 (E2P4)-treated ovariectomized mice.
      These experiments support the interpretation that macrophages are dispensable to
      regulation of proliferative events induced by steroid hormones in the cycling and
      early pregnant mouse uterus to establish the epithelial, stromal, and vascular
      architecture which is critical for normal reproductive competence.

PMID- 25061096
TI  - Functions and transcriptional regulation of thrombospondins and their
      interrelationship with fibroblast growth factor-2 in bovine luteal cells.
AB  - Previously, we showed luteal stage-specific regulation of angiogenesis-modulating
      factors by prostaglandin F2 alpha (PGF2alpha). Fibroblast growth factor 2 (FGF2)
      and thrombospondins (THBSs) exhibited the most divergent profile of induction by
      PGF2alpha. We therefore examined the transcriptional regulation and roles of
      THBSs in luteal cells and studied their interaction with FGF2. THBSs and their
      receptors exhibited cell-specific expression: THBS1 was the predominant form in
      luteal endothelial cells (LEC), whereas luteinized granulosa cells (LGC)
      expressed mostly THBS2. CD36 was confined to LGC, but CD47 did not exhibit
      preferential expression between LEC and LGC. THBS1 and THBS2 were both stimulated
      in vitro by PGF2a and its analog in LGC. In contrast, luteinizing signals (LH and
      insulin) decreased the expression of THBS1, THBS2, and CD36. Importantly, LH
      increased FGF2 expression, suggesting that THBSs and FGF2 are conversely
      regulated. We found that FGF2 inhibited THBS1 and vice versa, and that THBS1
      treatment decreased FGF2 expression, suggesting reciprocal inhibition. In
      agreement, ablation of THBS1 by specific small interference RNAs elevated FGF2
      levels. THBS1 reduced LEC numbers and promoted apoptosis by activation of caspase
      3. In contrast, FGF2 reduced basal and THBS1-induced caspase-3 levels. Consistent
      with these findings, small interference RNA silencing of THBS1 in luteal cells
      reduced the levels of active caspase-3 and improved the survival of cells when
      challenged with staurosporine. Taken together, these studies suggest that THBSs
      are suppressed during luteinization but are induced by PGF2alpha in luteolysis.
      THBS1 has antiangiogenic, proapoptotic properties; these, together with its
      ability to inhibit FGF2 expression and activity, can promote luteolysis. 

PMID- 25061097
TI  - Comparison of the absolute level of epigenetic marks 5-methylcytosine, 5
      hydroxymethylcytosine, and 5-hydroxymethyluracil between human leukocytes and
      sperm.
AB  - 5-Methylcytosine is one of the most important epigenetic modifications and has a
      profound impact on embryonic development. After gamete fusion, there is a
      widespread and rapid active demethylation process of sperm DNA, which suggests
      that the paternal epigenome has an important role during embryonic development.
      To better understand the epigenome of sperm DNA and its possible involvement in a
      developing embryo, we determined epigenetic marks in human sperm DNA and in
      surrogate somatic tissue leukocytes; the analyzed epigenetic modifications
      included 5-methyl-2'-deoxycytidine, 5-hydroxymethyl-2'-deoxycytidine, and 5
      hydroxymethyl-2'-deoxyuridine. For absolute determination of the modification, we
      used liquid chromatography with UV detection and tandem mass spectrometry
      techniques with isotopically labeled internal standards. Our analyses
      demonstrated, for the first time to date, that absolute global values of 5-methyl
      2'-deoxycytidine, 5-hydroxymethyl-2'-deoxycytidine, and 5-hydroxymethyl-2'
      deoxyuridine in sperm are highly statistically different from those observed for
      leukocyte DNA, with respective mean values of 3.815% versus 4.307%, 0.797 versus
      2.945 per 104 deoxynucleosides, and 5.209 versus 0.492 per 106 deoxynucleosides.
      We hypothesize that an exceptionally high value of 5-hydroxymethyluracil in sperm
      (>10-fold higher than in leukocytes) may play a not yet recognized regulatory
      role in the paternal genome.

PMID- 25061098
TI  - Functional role of arginine during the peri-implantation period of pregnancy. II.
      Consequences of loss of function of nitric oxide synthase NOS3 mRNA in ovine
      conceptus trophectoderm.
AB  - Nitric oxide (NO) is a gaseous molecule that regulates angiogenesis and
      vasodilation via activation of the cGMP pathway. However, functional roles of NO
      during embryonic development from spherical blastocysts to elongated filamentous
      conceptuses (embryo and extraembryonic membrane) during the peri-implantation
      period of pregnancy have not been elucidated in vivo. In order to assess roles of
      NO production in survival and development of the ovine conceptus, we conducted an
      in vivo morpholino antisense oligonucleotide (MAO)-mediated knockdown trial of
      nitric oxide synthase-3 (NOS3) mRNA, the major isoform of NO synthase, in ovine
      conceptus trophectoderm (Tr). Translational knockdown of NOS3 mRNA results in
      small, thin, and underdeveloped conceptuses, but normal production of interferon
      tau, the pregnancy recognition signal in sheep. MAO-NOS3 knockdown in conceptuses
      decreased the abundance of NOS3 (72%, P < 0.05) and the arginine transporter
      SLC7A1 proteins in conceptus Tr. Furthermore, the amounts of ornithine and
      polyamines were less (P < 0.01) in uterine fluid, whereas the amounts of arginine
      (58%, P < 0.01), citrulline (68%, P < 0.05), ornithine (68%, P < 0.001),
      glutamine (78%, P < 0.001), glutamate (68%, P < 0.05), and polyamines (P < 0.01)
      were less in conceptuses, which likely accounts for the failure of MAO-NOS3
      conceptuses to develop normally. For MAO-NOS3 conceptuses, there were no
      compensatory increases in the expression levels of either nitric oxide synthase-1
      (NOS1) or nitric oxide synthase-2 (NOS2) or in expression of enzymes for
      synthesis of polyamines (ornithine decarboxylase, arginine decarboxylase,
      agmatinase) from arginine or ornithine with which to rescue development of MAO
      NOS3 conceptuses. Thus, the adverse effect of MAO-NOS3 to reduce NO generation
      and the transport of arginine and ornithine into conceptuses is central to an
      explanation for failure of normal development of MAO-NOS3, compared to control
      conceptuses. The study, for the first time, created an NO-deficient mammalian
      conceptus model in vivo and provided new insights into the orchestrated events of
      conceptus development during the peri-implantation period of pregnancy. Our data
      suggest that NOS3 is the key enzyme for NO production by conceptus Tr and that
      this protein also regulates the availability of arginine in conceptus tissues for
      synthesis of polyamines that are essential for conceptus survival and
      development. 

PMID- 25061100
TI  - Risk factors for sleep-disordered breathing in pregnancy.

PMID- 25061099
TI  - Adrenomedullin promotes rat trophoblast stem cell differentiation.
AB  - Accumulating data suggest that adrenomedullin (ADM) regulates the trophoblast
      cell growth, migration, and invasion. However, the effect of ADM on trophoblast
      differentiation is poorly understood. In this study, we hypothesized that ADM
      promotes the differentiation of trophoblast stem cells (TSCs) into trophoblast
      giant cells (TGCs). Using rat TSCs, Rcho-1 cells, we investigated the effect of
      ADM on TSC differentiation into TGCs in differentiation or stem cell media,
      respectively, and explored the effect of ADM on the mechanistic target of
      rapamycin (MTOR) signaling in trophoblast cell differentiation. The results
      include: 1) in the presence of differentiation medium, 10-7 M ADM, but not lower
      doses, elevated (P < 0.05) Prl3b1/Esrrb (i.e., the ratio of mRNA levels) by 1.7
      fold compared to that in control; 2) the supplementation of ADM antagonist,
      regardless of the concentration of ADM, reduced (P < 0.05) Prl3b1/Esrrb by 2
      fold, compared to control group, while the supplementation of CGRP antagonist,
      regardless of the concentration of ADM, did not change Prl3b1/Esrrb; 3) in the
      presence of stem cell medium, ADM did not alter the expression of TSC and TGC
      marker genes, however, the ratio of Prl3b1/Esrrb was reduced (P < 0.05) by ADM
      antagonist compared to that in control; and 4) ADM increased (P < 0.05)
      phosphorylated MTOR proteins and the ratio of phosphorylated to total MTOR
      proteins by 2.0- and 1.7-fold, respectively. The results indicate that ADM
      promotes but does not induce the differentiation of TSCs to TGCs in a dose
      dependent manner and MTOR signaling may play a role in this process.

PMID- 25061101
TI  - Targeting mTORC1-mediated metabolic addiction overcomes fludarabine resistance in
      malignant B cells.
AB  - MTOR complex-1(mTORC1) activation occurs frequently in cancers, yet clinical
      efficacy of rapalogs is limited because of the associated activation of upstream
      survival pathways. An alternative approach is to inhibit downstream of mTORC1;
      therefore, acquired resistance to fludarabine (Flu), a purine analogue and
      antimetabolite chemotherapy, active agent for chronic lymphocytic leukemia (CLL)
      was investigated. Elevated phospho-p70S6K, also known as RPS6KB1 (ribosomal
      protein S6 kinase, 70kDa, polypeptide 1) (T389), an mTORC1 activation marker,
      predicted Flu resistance in a panel of B-cell lines, isogenic Flu-resistant
      (FluR) derivatives, and primary human CLL cells. Consistent with the anabolic
      role of mTORC1, FluR cells had higher rates of glycolysis and oxidative
      phosphorylation than Flu-sensitive (FluS) cells. Rapalogs (everolimus and
      rapamycin) induced moderate cell death in FluR and primary CLL cells, and
      everolimus significantly inhibited glycolysis and oxidative phosphorylation in
      FluR cells. Strikingly, the higher oxidative phosphorylation in FluR cells was
      not coupled to higher ATP synthesis. Instead, it contributed primarily to an
      essential, dihydroorotate dehydrogenase catalyzed, step in de novo pyrimidine
      biosynthesis. mTORC1 promotes pyrimidine biosynthesis by p70S6 kinase-mediated
      phosphorylation of CAD (carbamoyl-phosphate synthetase 2, aspartate
      transcarbamylase, and dihydroorotase; Ser1859) and favors S-phase cell-cycle
      progression. We found increased phospho-CAD (S1859) and higher S-phase population
      in FluR cells. Pharmacological inhibition of de novo pyrimidine biosynthesis
      using N-phosphonacetyl-l-aspartate and leflunomide, RNAi-mediated knockdown of
      p70S6K, and inhibition of mitochondrial respiration were selectively cytotoxic to
      FluR, but not FluS, cells. These results reveal a novel link between mTORC1
      mediated metabolic reprogramming and Flu resistance identifying mitochondrial
      respiration and de novo pyrimidine biosynthesis as potential therapeutic targets.
      IMPLICATIONS: This study provides the first evidence for mTORC1/p70S6K-dependent
      regulation of pyrimidine biosynthesis in a relevant disease setting.

PMID- 25061102
TI  - FOXD3 modulates migration through direct transcriptional repression of TWIST1 in
      melanoma.
AB  - The neural crest is a multipotent, highly migratory cell population that gives
      rise to diverse cell types, including melanocytes. Factors regulating the
      development of the neural crest and emigration of its cells are likely to
      influence melanoma metastasis. The transcription factor FOXD3 plays an essential
      role in premigratory neural crest development and has been implicated in melanoma
      cell dormancy and response to therapeutics. FOXD3 is downregulated during the
      migration of the melanocyte lineage from the neural crest, and our previous work
      supports a role for FOXD3 in suppressing melanoma cell migration and invasion.
      Alternatively, TWIST1 is known to have promigratory and proinvasive roles in a
      number of cancers, including melanoma. Using ChIP-seq analysis, TWIST1 was
      identified as a potential transcriptional target of FOXD3. Mechanistically, FOXD3
      directly binds to regions of the TWIST1 gene locus, leading to transcriptional
      repression of TWIST1 in human mutant BRAF melanoma cells. In addition, depletion
      of endogenous FOXD3 promotes upregulation of TWIST1 transcripts and protein.
      Finally, FOXD3 expression leads to a significant decrease in cell migration that
      can be efficiently reversed by the overexpression of TWIST1. These findings
      uncover the novel interplay between FOXD3 and TWIST1, which is likely to be
      important in the melanoma metastatic cascade. IMPLICATIONS: FOXD3 and TWIST1
      define distinct subgroups of cells within a heterogeneous tumor.

PMID- 25061103
TI  - Cytoskeletal regulatory gene expression and migratory properties of B-cell
      progenitors are affected by the ETV6-RUNX1 rearrangement.
AB  - Although the ETV6-RUNX1 fusion is a frequent initiating event in childhood
      leukemia, its role in leukemogenesis is only partly understood. The main impact
      of the fusion itself is to generate and sustain a clone of clinically silent
      preleukemic B-cell progenitors (BCP). Additional oncogenic hits, occurring even
      several years later, are required for overt disease. The understanding of the
      features and interactions of ETV6-RUNX1-positive cells during this "latency"
      period may explain how these silent cells can persist and whether they could be
      prone to additional genetic changes. In this study, two in vitro murine models
      were used to investigate whether ETV6-RUNX1 alters the cellular adhesion and
      migration properties of BCP. ETV6-RUNX1-expressing cells showed a significant
      defect in the chemotactic response to CXCL12, caused by a block in CXCR4
      signaling, as demonstrated by inhibition of CXCL12-associated calcium flux and
      lack of ERK phosphorylation. Moreover, the induction of ETV6-RUNX1 caused changes
      in the expression of cell-surface adhesion molecules. The expression of genes
      regulating the cytoskeleton was also affected, resulting in a block of CDC42
      signaling. The abnormalities described here could alter the interaction of ETV6
      RUNX1 preleukemic BCP with the microenvironment and contribute to the
      pathogenesis of the disease. IMPLICATIONS: Alterations in the expression of
      cytoskeletal regulatory genes and migration properties of BCP represent early
      events in the evolution of the disease, from the preleukemic phase to the
      clinical onset, and suggest new strategies for effective eradication of leukemia.

PMID- 25061104
TI  - SMAD4 suppresses AURKA-induced metastatic phenotypes via degradation of AURKA in
      a TGFbeta-independent manner.
AB  - SMAD4 has been suggested to inhibit the activity of the WNT/beta-catenin
      signaling pathway in cancer. However, the mechanism by which SMAD4 antagonizes
      WNT/beta-catenin signaling in cancer remains largely unknown. Aurora A kinase
      (AURKA), which is frequently overexpressed in cancer, increases the
      transcriptional activity of beta-catenin/T-cell factor (TCF) complex by
      stabilizing beta-catenin through the inhibition of GSK-3beta. Here, SMAD4
      modulated AURKA in a TGFbeta-independent manner. Overexpression of SMAD4
      significantly suppressed AURKA function, including colony formation, migration,
      and invasion of cell lines. In addition, SMAD4 bound to AURKA induced degradation
      of AURKA by the proteasome. A luciferase activity assay revealed that the
      transcriptional activity of the beta-catenin/TCF complex was elevated by AURKA,
      but decreased by SMAD4 overexpression. Moreover, target gene analysis showed that
      SMAD4 abrogated the AURKA-mediated increase of beta-catenin target genes.
      However, this inhibitory effect of SMAD4 was abolished by overexpression of AURKA
      or silencing of AURKA in SMAD4-overexpressed cells. Meanwhile, the SMAD4-mediated
      repression of AURKA and beta-catenin was independent of TGFbeta signaling because
      blockage of TGFbetaR1 or restoration of TGFbeta signaling did not prevent
      suppression of AURKA and beta-catenin signaling by SMAD4. These results indicate
      that the tumor-suppressive function of SMAD4 is mediated by downregulation of
      beta-catenin transcriptional activity via AURKA degradation in a TGFbeta
      independent manner. IMPLICATIONS: SMAD4 interacts with AURKA and antagonizes its
      tumor-promoting potential, thus demonstrating a novel mechanism of tumor
      suppression.

PMID- 25061105
TI  - Letter to the editor.

PMID- 25061106
TI  - Advances in G protein-coupled receptor allostery: from function to structure.
AB  - It is now widely accepted that G protein-coupled receptors (GPCRs) are highly
      dynamic proteins that adopt multiple active states linked to distinct functional
      outcomes. Furthermore, these states can be differentially stabilized not only by
      orthosteric ligands but also by allosteric ligands acting at spatially distinct
      binding sites. The key pharmacologic characteristics of GPCR allostery include
      improved selectivity due to either greater sequence divergence between receptor
      subtypes and/or subtype-selective cooperativity, a ceiling level to the effect,
      probe dependence (whereby the magnitude and direction of the allosteric effect
      change with the nature of the interacting ligands), and the potential for biased
      signaling. Recent chemical biology developments are beginning to demonstrate how
      the incorporation of analytical pharmacology and operational modeling into the
      experimental workflow can enrich structure-activity studies of allostery and
      bias, and have also led to the discovery of a new class of hybrid
      orthosteric/allosteric (bitopic) molecules. The potential for endogenous
      allosteric modulators to play a role in physiology and disease remains to be
      fully appreciated but will likely represent an important area for future studies.
      Finally, breakthroughs in structural and computational biology are beginning to
      unravel the mechanistic basis of GPCR allosteric modulation at the molecular
      level. 

PMID- 25061107
TI  - Mycophenolic acid in the treatment of birdshot chorioretinopathy: long-term
      follow-up.
AB  - AIM: To assess the long-term efficacy and tolerability of both derivatives of
      mycophenolic acid, mycophenolate mofetil (MMF) and mycophenolate sodium (MPS), in
      the therapy of patients with birdshot chorioretinopathy (BSCR). METHODS:
      Retrospective analysis of 24 patients (48 eyes) with BSCR, treated with MMF or
      MPS with a follow-up of at least 1 year. The main outcome measures included
      control of inflammation, steroid-sparing potential and side effects. Secondary
      outcome measure was the development of retinal function during the therapy
      measured by best-corrected visual acuity (BCVA), visual field and/or
      electroretinography (ERG). RESULTS: Twelve patients (50%) were treated with MMF
      and 12 patients (50%) with MPS. Control of intraocular inflammation, defined as
      complete lack of clinical and angiographic signs of inflammatory activity, was
      achieved in 16 of 24 patients (67%). The angiographic signs of activity were
      significantly reduced during the follow-up (p<0.05). No significant difference
      was found in the mean BCVA, the visual field and the ERG parameters during the
      treatment compared with the baseline (p>0.05). In 20 out of 21 patients (95%) who
      received systemic corticosteroids, the corticosteroids could be tapered to a
      daily dose of <=10 mg (rate 0.26/patient-year). Drug-related side effects
      occurred in 12 patients (50%, rate 0.16/patient-year). In four patients (17%), a
      therapy switch from MMF to MPS was undertaken due to gastrointestinal discomfort.
      CONCLUSIONS: Derivatives of mycophenolic acid are effective and safe drugs for
      the treatment of BSCR. In cases with gastrointestinal side effects, a therapy
      switch from MMF to MPS should be considered.

PMID- 25061108
TI  - Descemet's stripping automated endothelial keratoplasty with anterior chamber
      intraocular lenses.

PMID- 25061110
TI  - Human recombinant cytochrome P450 enzymes display distinct hydrogen peroxide
      generating activities during substrate independent NADPH oxidase reactions.
AB  - Microsomal enzymes generate H2O2 in the presence of NADPH. In this reaction,
      referred to as "oxidase" activity, H2O2 is generated directly or indirectly via
      the formation of superoxide anion. In the presence of redox active transition
      metals, H2O2 can form highly toxic hydroxyl radicals and, depending on the
      "oxidase" activity of individual cytochrome P450 isoenzymes, this can compromise
      cellular functioning and contribute to tissue injury. In the present studies, we
      compared the initial rates of H2O2 generating activity of microsomal preparations
      containing various human recombinant cytochromes P450s. In the absence of
      cytochrome P450s the human recombinant NADPH cytochrome P450 reductase (CPR)
      generated low, but detectable amounts of H2O2 (~0.04 nmol H2O2/min/100 units of
      reductase). Significantly greater activity was detected in preparations
      containing individual cytochrome P450s coexpressed with CPR (from 6.0 nmol
      H2O2/min/nmol P450 to 0.2 nmol/min/nmol P450); CYP1A1 was the most active,
      followed by CYP2D6, CYP3A4, CYP2E1, CYP4A11, CYP1A2, and CYP2C subfamily enzymes.
      H2O2 generating activity of the cytochrome P450s was independent of the ratio of
      CYP/CPR. Thus, similar H2O2 generating activity was noted with the same
      cytochrome P450s (CYP3A4, CYP2E1, and CYP2C9) expressed at or near the ratio of
      CYP/CPR in human liver microsomes (5-7), and when CPR was present in excess
      (CYP/CPR = 0.2-0.3). Because CYP3A4/5/7 represent up to 40% of total cytochrome
      P450 in the liver, these data indicate that these enzymes are the major source of
      H2O2 in human liver microsomes. 

PMID- 25061109
TI  - Control of transcriptional repression of the vitellogenin receptor gene in
      largemouth bass (Micropterus salmoides) by select estrogen receptors isotypes.
AB  - The vitellogenin receptor (Vtgr) plays an important role in fish reproduction.
      This receptor functions to incorporate vitellogenin (Vtg), a macromolecule
      synthesized and released from the liver in the bloodstream, into oocytes where it
      is processed into yolk. Although studies have focused on the functional role of
      Vtgr in fish, the mechanistic control of this gene is still unexplored. Here we
      report the identification and analysis of the first piscine 5' regulatory region
      of the vtgr gene which was cloned from largemouth bass (Micropterus salmoides).
      Using this putative promoter sequence, we investigated a role for hormones,
      including insulin and 17beta-estradiol (E2), in transcriptional regulation
      through cell-based reporter assays. No effect of insulin was observed, however,
      E2 was able to repress transcriptional activity of the vtgr promoter through
      select estrogen receptor subtypes, Esr1 and Esr2a but not Esr2b. Electrophoretic
      mobility shift assay demonstrated that Esr1 likely interacts with the vtgr
      promoter region through half ERE and/or SP1 sites, in part. Finally we also show
      that ethinylestradiol (EE2), but not bisphenol-A (BPA), represses promoter
      activity similarly to E2. These results reveal for the first time that the Esr1
      isoform may play an inhibitory role in the expression of LMB vtgr mRNA under the
      influence of E2, and potent estrogens such as EE2. In addition, this new evidence
      suggests that vtgr may be a target of select endocrine disrupting compounds
      through environmental exposures. 

PMID- 25061111
TI  - Oxidative stress and aromatic hydrocarbon response of human bronchial epithelial
      cells exposed to petro- or biodiesel exhaust treated with a diesel particulate
      filter.
AB  - The composition of diesel exhaust has changed over the past decade due to the
      increased use of alternative fuels, like biodiesel, and to new regulations on
      diesel engine emissions. Given the changing nature of diesel fuels and diesel
      exhaust emissions, a need exists to understand the human health implications of
      switching to "cleaner" diesel engines run with particulate filters and engines
      run on alternative fuels like biodiesel. We exposed well-differentiated normal
      human bronchial epithelial cells to fresh, complete exhaust from a diesel engine
      run (1) with and without a diesel particulate filter and (2) using either
      traditional petro- or alternative biodiesel. Despite the lowered emissions in
      filter-treated exhaust (a 91-96% reduction in mass), significant increases in
      transcripts associated with oxidative stress and polycyclic aromatic hydrocarbon
      response were observed in all exposure groups and were not significantly
      different between exposure groups. Our results suggest that biodiesel and filter
      treated diesel exhaust elicits as great, or greater a cellular response as
      unfiltered, traditional petrodiesel exhaust in a representative model of the
      bronchial epithelium. 

PMID- 25061112
TI  - Bevacizumab reduces neurocan content and gene expression in newborn rat retina in
      vitro.
AB  - PURPOSE: Extracellular matrix (ECM) and cellular membrane proteoglycans (PGs)
      play important roles in neural differentiation and cell adhesion. Vascular
      endothelial growth factor, an important signal protein in vascular and retinal
      neural cell development, is retained in the ECM due to its high affinity for PG.
      Bevacizumab, an anti-VEGF agent, has been extensively used for treating retinal
      diseases in adult and newborn patients, although its effect on the developing
      retina remains largely unknown. The purpose of this study was to investigate the
      effect of bevacizumab on neurocan, phosphacan, and syndecan-3 PG levels in
      newborn rat retina. METHODS: Retinal explants of sixty 2-day-old Lister hooded
      rats were obtained after eye enucleation and maintained in culture media with or
      without bevacizumab for 48 hours. Immunohistochemical staining was assessed
      against neurocan, phosphacan, and syndecan-3. Proteoglycan content was quantified
      based on the intensity of immunohistochemical labeling. Gene expressions were
      quantified by real-time reverse-transcription polymerase chain reaction. The
      results from the treatment and control groups were compared. RESULTS: No
      significant difference in the staining intensity and mRNA expression of
      phosphacan and syndecan-3 was observed between the groups. However, a significant
      decrease in neurocan content and mRNA expression was observed in bevacizumab
      treated retinal explants compared with controls. CONCLUSIONS: Bevacizumab did not
      affect phosphacan and syndecan-3 levels but decreased neurocan content and gene
      expression. Therefore, it may interfere with early postnatal retinal cell
      differentiation. Although further studies are necessary to confirm our findings,
      we suggest anti-VEGF agents be used with caution in developing retinal tissue.

PMID- 25061113
TI  - The roles of urokinase-type plasminogen activator in leukocyte infiltration and
      inflammatory responses in mice corneas treated with lipopolysaccharide.
AB  - PURPOSE: Urokinase-type plasminogen activator (u-PA) plays an important role in
      corneal wound healing, yet its role in corneal inflammation remains poorly
      understood. We investigated the role of u-PA in a murine model of
      lipopolysaccharide (LPS)-induced corneal inflammation. METHODS: The corneal
      epithelium was scraped and LPS was applied to u-PA wild-type (u-PA(+/+)) and u-PA
      deficient (u-PA(-/-)) mice. Corneal re-epithelialization and opacity were
      measured by stereomicroscopy. Fibrin zymography was performed to detect
      plasminogen activators in corneas from u-PA(+/+) and u-PA(-/-) mice. Neutrophil,
      macrophage, and u-PA receptor (u-PAR) expression were determined by
      immunohistochemistry. Gene expression of corneal macrophage chemoattractant
      protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 was assessed with
      reverse transcription-polymerase chain reaction. The in vitro effects of
      endogenous u-PA on MCP-1, MIP-2, matrix metalloproteinase (MMP)-2, and MMP-9
      expression, and macrophage migration activity in mouse ocular fibroblasts
      stimulated by LPS, were examined. RESULTS: The u-PA(+/+) mice showed enhanced
      corneal inflammation as compared with u-PA(-/-) mice. The u-PA expression was
      increased by LPS stimulation. Immunohistochemical analyses indicated that more
      neutrophils and macrophages were present in corneas from u-PA(+/+) mice than u
      PA(-/-) mice. The u-PAR expression was detected in inflammatory cells and in the
      leading edges of the epithelial migrating cells. Enhanced mRNA expression of MCP
      1 and MIP-2 was observed in corneas from u-PA(+/+) mice compared to u-PA(-/-)
      mice. Macrophage chemoattractant protein-1, MIP-2, and MMP-9, but not MMP-2,
      significantly increased in corneal fibroblasts from u-PA(+/+) mice compared with
      u-PA(-/-) mice. CONCLUSIONS: These data indicate that u-PA promotes LPS-induced
      leukocyte infiltration in cornea and that u-PA is an important component in LPS
      induced corneal inflammatory responses.

PMID- 25061115
TI  - Visual acuity and increased mortality: the role of allostatic load and functional
      status.
AB  - PURPOSE: Poor vision may detrimentally impact functional status and affect
      allostatic load (AL), a measure of cumulative physiological wear and tear on the
      body's regulatory systems. We examined the direct effects of visual acuity (VA)
      on mortality and its indirect effect on mortality through its impact on
      functional status and AL in older adults. METHODS: Data from 4981 participants
      (age >= 60 years) from the 1999-2004 National Health and Nutrition Examination
      Survey (NHANES) with mortality linkage through 2006 were analyzed. Functional
      status was assessed by activities of daily living (ADL) and instrumental
      activities of daily living (IADL). The AL index was composed of 10 biomarkers:
      systolic and diastolic blood pressures, body mass index (BMI), glycosylated
      hemoglobin, total cholesterol, triglycerides, albumin, C-reactive protein,
      homocysteine, and creatinine clearance. Visual acuity was categorized as no
      (20/20-20/25), mild (20/30-20/40), moderate (20/50-20/80), or severe (>=20/200)
      visual impairment. Structural equation modeling using three mediating variables
      representing ADL, IADL, and AL examined the effects of VA on all-cause and
      cardiovascular disease (CVD)-related mortality. RESULTS: Adjusting for all
      covariates, a one-unit change in VA category increased mortality risk (hazard
      ratio [HR] = 1.17; 95% confidence interval [CI] 1.05, 1.32); IADL and AL
      predicted mortality (HR = 1.15; CI 1.10, 1.20 and HR = 1.13; CI 1.06, 1.20,
      respectively). Activities of daily living did not predict mortality (HR = 0.98;
      CI 0.91, 1.05). Worse VA was associated with increased AL (beta = 0.11; P =
      0.013) and worse IADL (beta = 1.06; P < 0.001). Worse VA increased mortality risk
      indirectly through AL (HR = 1.01; CI 1.00, 1.03) and IADL (HR = 1.16; CI 1.09,
      1.23). The total effect of VA on mortality including through IADL and AL was HR =
      1.38 (CI 1.23, 1.54). Similar but slightly stronger patterns of association were
      found when examining CVD-related mortality, but not cancer-related mortality.
      CONCLUSIONS: Allostatic load and particularly IADL may function as mediators
      between VA impairment and mortality. Older adults with VA impairment could
      potentially benefit from interventions designed to prevent IADL functional status
      decline to reduce the risk of mortality.

PMID- 25061114
TI  - Elevated transforming growth factor beta1 in plasma of primary open-angle
      glaucoma patients.
AB  - PURPOSE: To test the hypothesis that primary open-angle glaucoma (POAG) patients
      have a systemic elevation of transforming growth factor beta1 (TGFbeta1).
      METHODS: Plasma was prepared from blood samples drawn from patients of the
      Vanderbilt Eye Institute during clinic visits. Concentrations of total TGFbeta1
      and thrombospondin-1 (TSP1) in plasma were determined by ELISA. Statistical
      significance of differences between POAG and control samples was evaluated by
      Mann-Whitney test. Regression analysis was used to evaluate correlations between
      plasma TGFbeta1 and patient age and between plasma TGFbeta1 and TSP1. RESULTS:
      Plasma samples were obtained from 148 POAG patients and 150 controls.
      Concentration of total TGFbeta1 in the plasma of POAG patients (median = 3.25
      ng/mL) was significantly higher (P < 0.0001) than in controls (median = 2.46
      ng/mL). Plasma TGFbeta1 was not correlated with age of patient (P = 0.17).
      Thrombospondin-1 concentration was also significantly higher (P < 0.0001) in POAG
      patients (median = 0.774 MUg/mL) as compared to controls (median = 0.567 MUg/mL).
      Plasma total TGFbeta1 and TSP1 concentrations were linearly correlated (P <
      0.0001). CONCLUSIONS: Plasma samples from POAG patients display elevated total
      TGFbeta1 compared to controls, consistent with elevated systemic TGFbeta1 in POAG
      patients.

PMID- 25061116
TI  - Quantitative regional differences in corneal endothelial abnormalities in the
      central and peripheral zones in Fuchs' endothelial corneal dystrophy.
AB  - PURPOSE: To quantitate the regional corneal differences in endothelial
      abnormalities in Fuchs' endothelial corneal dystrophy at multiple sites,
      including the peripheral zone. METHODS: Forty-one eyes of 23 patients with Fuchs'
      endothelial corneal dystrophy were studied at Osaka University Hospital. The
      sizes of the areas of degeneration resulting from guttae were measured using a
      new noncontact specular microscope in the central cornea, the paracentral zone
      0.6 mm from the center, and the peripheral zone 3.7 mm peripheral to the center.
      RESULTS: The percentages of the images covered by the abnormal areas were 71% +/-
      36% in the center, 68% +/- 35% in the paracentral zone, and 33% +/- 36% in the
      peripheral zone. The values in the peripheral zone were significantly (P < 0.001)
      smaller than in the center and paracentral zones. The percentage of the abnormal
      area in the peripheral zone was correlated significantly (P < 0.001, R(2) =
      0.452) with the disease grade in advanced cases, whereas those in the center or
      paracentral zones were not. Among the areas of the peripheral zone, the abnormal
      inferotemporal areas were significantly (P < 0.001) larger than superonasally.
      CONCLUSIONS: In Fuchs' endothelial corneal dystrophy, the corneal endothelium is
      damaged more severely in the center and paracentral zones than in the peripheral
      zone, and peripheral measurement can objectively grade the disease. In the
      peripheral zones, the inferotemporal endothelium is damaged more severely. These
      findings might provide a new understanding of the disease mechanisms.

PMID- 25061117
TI  - Effect of vitamin D receptor knockout on cornea epithelium wound healing and
      tight junctions.
AB  - PURPOSE: Our laboratory previously determined that vitamin D3, the vitamin D
      receptor (VDR), and 1alpha hydroxylase are present and active in the eye. In this
      study, we examined the effects of VDR knockout on wound healing, the tight
      junction-associated proteins occludin and ZO-1, and tight junction numbers in
      mouse corneas. METHODS: Epithelial wounds (2-mm) were made with an agar brush on
      4-week-old and 10-week-old wild-type, heterozygous, and VDR knockout mouse
      corneas. Mice were on a normal or high lactose, Ca(2+), and PO4(-) diet. Wound
      healing area was measured over time. Real-time PCR was used to quantify occludin
      and ZO-1 message expression. Western blot was used for protein expression.
      Transmission electron microscopy was used to examine corneal epithelium and
      endothelium tight junctions. Immunofluorescence was used to examine epithelial ZO
      1 distribution. RESULTS: Results showed a decreased healing rate in 10-week-old
      VDR knockout mice compared with wild-types. Vitamin D receptor knockout mice on
      the special diet had no difference in healing rate compared with wild-types. Real
      time PCR showed decreased expression of occludin and ZO-1 in 10-week-old VDR
      knockout mice compared with wild-types. Western blot of 10-week-old knockout
      mouse corneas showed decreased occludin expression compared with wild-types.
      Transmission electron microscopy showed a significant difference in tight
      junction numbers in VDR knockouts versus wild-types. Immunofluorescence showed a
      change in ZO-1 distribution among genotypes. CONCLUSIONS: Vitamin D receptor
      knockout affects mouse corneal epithelium wound healing and tight junction
      integrity.

PMID- 25061118
TI  - Misuse of benzodiazepines and Z-drugs in the UK.
AB  - Benzodiazepines and Z-drugs are commonly prescribed for insomnia and anxiety
      syndromes and there is increasing concern regarding their misuse. Using an
      internet-based questionnaire we found that of 1500 respondents 7.7% (n = 116) had
      misused one or more of these medications. Almost 15% of those misusing at least
      one of these drugs did so once weekly or more often. The main reasons reported
      for their use were to help sleep (66.4%), to cope with stress (37.1%) and/or to
      get high (31.0%). A total of 31% obtained the medications from multiple sources;
      healthcare professionals (55.2%) and friends/family (39.7%) most commonly. Our
      study can be used to inform prevention measures for their misuse. 

PMID- 25061119
TI  - Mental and physical illness in caregivers: results from an English national
      survey sample.
AB  - BACKGROUND: Caregivers make a significant and growing contribution to the social
      and medical care of people with long-standing disorders. The effective provision
      of this care is dependent on their own continuing health. AIMS: To investigate
      the relationship between weekly time spent caregiving and psychiatric and
      physical morbidity in a representative sample of the population of England.
      METHOD: Primary outcome measures were obtained from the Adult Psychiatric
      Morbidity Survey 2007. Self-report measures of mental and physical health were
      used, along with total symptom scores for common mental disorder derived from the
      Clinical Interview Schedule-Revised. RESULTS: In total, 25% (n = 1883) of the
      sample identified themselves as caregivers. They had poorer mental health and
      higher psychiatric symptom scores than non-caregivers. There was an observable
      decline in mental health above 10 h per week. A twofold increase in psychiatric
      symptom scores in the clinical range was recorded in those providing care for
      more than 20 h per week. In adjusted analyses, there was no excess of physical
      disorders in caregivers. CONCLUSIONS: We found strong evidence that caregiving
      affects the mental health of caregivers. Distress frequently reaches clinical
      thresholds, particularly in those providing most care. Strategies for maintaining
      the mental health of caregivers are needed, particularly as demographic changes
      are set to increase involvement in caregiving roles.

PMID- 25061122
TI  - Sleep disorders of Whipple's disease of the brain.
AB  - OBJECTIVE: To understand the effects of Whipple's disease (WD) of the brain on
      sleep function. METHODS: Clinical and polysomnographic studies of two patients
      with severe disruption of sleep due to WD: a 48-year-old female with primary WD
      of the brain and a 41-year-old male with secondary WD of the brain. RESULTS: The
      patient with primary WD had hypersomnolence with severe obstructive sleep apnoea,
      reduced sleep efficiency, frequent waking and sleep fragmentation. The patient
      with secondary WD was also hypersomnolent with oculomastictory myorhythmia. He
      was shown to have severe sleep initiation insomnia with poor sleep efficiency,
      severe obstructive sleep apnoea/hypopnoea and oculomasticatory myorhythmia at
      sleep-wake transitions. CONCLUSION: WD of the brain may affect sleep biology in
      its primary and secondary forms leading to hypersomnolence from obstructive sleep
      apnoea, sleep fragmentation, reduced sleep efficiency, sleep initiation insomnia
      and intrusive oculomasticatory myorhythmia.

PMID- 25061120
TI  - Behavioural and psychiatric symptoms in people with dementia admitted to the
      acute hospital: prospective cohort study.
AB  - BACKGROUND: Dementia is common in older people admitted to acute hospitals. There
      are concerns about the quality of care they receive. Behavioural and psychiatric
      symptoms of dementia (BPSD) seem to be particularly challenging for hospital
      staff. AIMS To define the prevalence of BPSD and explore their clinical
      associations. METHOD: Longitudinal cohort study of 230 people with dementia, aged
      over 70, admitted to hospital for acute medical illness, and assessed for BPSD at
      admission and every 4 (+/- 1) days until discharge. Other measures included
      length of stay, care quality indicators, adverse events and mortality. RESULTS:
      Participants were very impaired; 46% at Functional Assessment Staging Scale
      (FAST) stage 6d or above (doubly incontinent), 75% had BPSD, and 43% had some
      BPSD that were moderately/severely troubling to staff. Most common were
      aggression (57%), activity disturbance (44%), sleep disturbance (42%) and anxiety
      (35%). CONCLUSIONS: We found that BPSD are very common in older people admitted
      to an acute hospital. Patients and staff would benefit from more specialist
      psychiatric support.

PMID- 25061123
TI  - A slight increase within the normal range of serum uric acid and the decline in
      renal function: associations in a community-based population.
AB  - BACKGROUND: Hyperuricemia is a risk factor for adverse renal outcomes in patients
      with chronic kidney disease. This study investigated the effect of uric acid on
      renal function in a community-based population. METHODS: We used a nationwide
      database of 165 847 subjects (aged 29-74, male 40%) who participated in the
      annual 'Specific Health Check and Guidance in Japan' checkup between 2008 and
      2010; we examined the relationship between serum uric acid levels at baseline and
      2-year change in the estimated glomerular filtration rate (eGFR) obtained by
      using the Japanese equation. RESULTS: After adjusting for possible confounders,
      the eGFR change was inversely correlated with uric acid at baseline. In the
      multivariable analysis, the decline in eGFR was significantly more rapid in
      subjects with the slight increase in uric acid (males >=5.7 mg/dL, females >=4.4
      mg/dL), and the risk for incidental renal insufficiency (eGFR <60 mL/min/1.73
      m(2)) was increased at uric acid of >=6.3 mg/dL in males and >=5.5 mg/dL in
      females, compared with the lowest quintile. The multiple linear regression
      analysis revealed that the effect of uric acid on eGFR changes was significant,
      especially in females, those with proteinuria and diabetes and those without
      alcohol consumption. CONCLUSION: This study showed that serum uric acid is
      independently associated with a more rapid decline of eGFR and incident renal
      insufficiency, and that a slight increase within the normal range of serum uric
      acid might be a risk for renal damage in the general population.

PMID- 25061124
TI  - End-stage kidney disease due to Alport syndrome: outcomes in 296 consecutive
      Australia and New Zealand Dialysis and Transplant Registry cases.
AB  - BACKGROUND: Alport syndrome is a rare inheritable renal disease. Clinical
      outcomes for patients progressing to end-stage kidney disease (ESKD) are not well
      described. METHODS: This study aimed to investigate the characteristics and
      clinical outcomes of patients from Australia and New Zealand commencing renal
      replacement therapy (RRT) for ESKD due to Alport syndrome between 1965 and 1995
      (early cohort) and between 1996 and 2010 (contemporary cohort) compared with
      propensity score-matched, RRT-treated, non-Alport ESKD controls. RESULTS: A total
      of 58 422 patients started RRT during this period of which 296 (0.5%) patients
      had Alport ESKD. In the early cohort, Alport ESKD was associated with superior
      dialysis patient survival [adjusted hazard ratio (HR): 0.41, 95% confidence
      interval (CI): 0.20-0.83, P = 0.01], renal allograft survival (HR: 0.74, 95% CI:
      0.54-1.01, P = 0.05) and renal transplant patient survival (HR: 0.43, 95% CI:
      0.28-0.66, P < 0.001) compared with controls. In the contemporary cohort, no
      differences were observed between the two groups for dialysis patient survival
      (HR: 1.42, 95% CI: 0.65-3.11, P = 0.38), renal allograft survival (HR: 1.01, 95%
      CI: 0.57-1.79, P = 0.98) or renal transplant patient survival (HR: 0.67, 95% CI:
      0.26-1.73, P = 0.41). One Alport patient (0.4%) had post-transplant anti
      glomerular basement membrane (anti-GBM) disease. Four female and 41 male Alport
      patients became parents on RRT with generally good neonatal outcomes. CONCLUSION:
      Alport syndrome patients experienced comparable dialysis and renal transplant
      outcomes to matched non-Alport ESKD controls in the contemporary cohort due to
      relatively greater improvements in outcomes for non-Alport ESKD patients over
      time. Post-transplant anti-GBM disease was rare.

PMID- 25061125
TI  - The influence of birthweight, past poststreptococcal glomerulonephritis and
      current body mass index on levels of albuminuria in young adults: the
      multideterminant model of renal disease in a remote Australian Aboriginal
      population with high rates of renal disease and renal failure.
AB  - BACKGROUND: Australian Aborigines in remote areas have very high rates of kidney
      disease, which is marked by albuminuria. We describe a 'multihit' model of
      albuminuria in young adults in one remote Aboriginal community. METHODS: Urinary
      albumin/creatinine ratios (ACRs) were measured in 655 subjects aged 15-39 years
      and evaluated in the context of birthweights, a history of 'remote'
      poststreptococcal glomerulonephritis (PSGN; >=5 years earlier) and current body
      mass index (BMI). Birthweight had been <2.5 kg (low birthweight, LBW) in 25.4% of
      subjects and 22.8% had a remote history of PSGN. RESULTS: ACR levels rose with
      age. It exceeded the microalbuminuria threshold in 33.6% of subjects overall (25%
      of males and 45% of females). In multivariate models, birthweight (inversely),
      remote PSGN and current BMI were all independent predictors of ACR levels. The
      effects of birthweight and PSGN and their combination were expressed through
      amplification of ACR levels in relation to age and around the group median BMI of
      20.8 kg/m(2). In people with BMI <20.8 (57.8% of all males and 40.3% of the
      females), LBW and PSGN alone had minimal effects on ACR, but in combination they
      strikingly amplified ACR in relation to age. Those with BMI >=20.8 (which
      included 42.2% of the males and 59.7% of the females) had higher ACR levels, and
      both LBW and a PSGN history, separately and in combination, were associated with
      striking further amplification of ACR in the context of age. CONCLUSION: Much of
      the great excess of disease in this population is explained by high rates of the
      early life risk factors, LBW and PSGN. Their effects are expressed through
      amplification of ACR in the context of increasing age and are further moderated
      by levels of current body size. Both early life risk factors are potentially
      modifiable.

PMID- 25061126
TI  - Use of vascular access for haemodialysis in Europe: a report from the ERA-EDTA
      Registry.
AB  - BACKGROUND: Although arteriovenous fistulas (AVFs) are actively promoted, their
      use at the start of haemodialysis (HD) seems to be decreasing worldwide. In this
      paper, we describe recent trends in incidence and prevalence of vascular access
      types in Europe from 2005 to 2009 and their relationship with patient
      characteristics and survival. METHODS: Ten European renal registries
      participating in the ERA-EDTA Registry provided data on incidence (n = 13,044)
      and/or prevalence (n = 75,715) of vascular access types. We used logistic
      regression to assess which factors influence the likelihood to be treated with an
      AVF rather than another type. RESULTS: The use of AVFs at the start of HD showed
      a significant decreasing trend from 42% in 2005 to 32% in 2009 (P < 0.0001),
      while the use of central venous catheters (CVCs) increased from 58 to 68% (P <
      0.0001). A similar evolution pattern was observed for the prevalence; use of AVFs
      decreased from 66 to 62% and use of CVCs increased from 28 to 32%. There was a
      large international variation in the use of the different vascular access types.
      Female patients [adjusted odds ratio: 0.84, 95% confidence interval (CI): 0.78
      0.90] and those >=80 years (0.77, 95% CI: 0.67-0.90) were least likely to start
      HD with an AVF. CONCLUSION: In Europe, there is a decreasing trend in the use of
      AVFs and an increasing trend in the use of CVCs at the start and after the start
      of HD. We cannot explain all between-country variations we found, and more
      research is needed to clarify how healthcare around vascular access is organized
      in Europe.

PMID- 25061127
TI  - Effects of intradialytic cycling compared with pedometry on physical function in
      chronic outpatient hemodialysis: a prospective randomized trial.
AB  - BACKGROUND: Individuals on hemodialysis have low physical function and activity
      levels. Clinical trials have shown improvements in these parameters with exercise
      programming. Pedometers have not been extensively evaluated in individuals on
      hemodialysis. This randomized clinical trial compared the effects of
      intradialytic cycling versus a pedometer program on physical function, physical
      activity and quality of life. METHODS: Sixty patients were randomly assigned to
      two study groups. The ergometer group cycled during each hemodialysis session for
      24 weeks. Pedometer participants followed a home-based walking program for 24
      weeks. The primary outcome was aerobic capacity [VO2peak and 6-minute walk (6MW)
      test]. Secondary outcomes included lower extremity strength [sit-to-stand (SS)
      test], flexibility [sit-and-reach (SR) test], physical activity (accelerometer)
      and health-related quality of life. Measurements were collected at baseline and
      at 12 and 24 weeks. RESULTS: At 12 and 24 weeks, there was no significant change
      in the VO2peak or 6MW test between or within study groups. SS testing in the
      ergometer group improved from 10.2 (SD 3.4) to 11.4 (SD 2.5) cycles from baseline
      to 24 weeks (P < 0.005). Similarly, in the pedometer group, SS cycles improved
      from 10.1 (SD 3.3) to 12.2 (SD 3.5) (P < 0.005). The SR test also significantly
      improved over time in both the study groups. No significant changes were noted
      for other secondary outcomes. CONCLUSIONS: Both intradialytic cycling and
      pedometer programming improved aspects of physical function. Neither intervention
      had a significant effect on aerobic capacity. No significant differences in any
      outcomes were identified between interventions groups.

PMID- 25061128
TI  - A comparison of radon and its decay products' behaviour in indoor air.
AB  - The inhalation of short-lived radon decay products (RDP) yields the greatest
      contribution to the natural radiation exposure. This paper deals with a study
      carried out to improve the knowledge of the behaviour of RDPs, their interaction
      with particulates and the plateout during the time. The tests confirmed that a
      high aerosol particle concentration increases the probability that an ion sticks
      to aerosol and remains long in the air, leading to both an increase of F and a
      decrease of fp, as reported in the literature. The same experimental protocol
      applied in a small radon chamber showed a strong reduction of the equilibrium
      factor (an average of ~10 %), because in a small environment the plateout
      phenomenon prevails on the attachment to particulate. 

PMID- 25061129
TI  - Development of a computer code to calculate the distribution of radionuclides
      within the human body by the biokinetic models of the ICRP.
AB  - This paper describes the Basic Radionuclide vAlue for Internal Dosimetry (BRAID)
      code, which was developed to calculate the time-dependent activity distribution
      in each organ and tissue characterised by the biokinetic compartmental models
      provided by the International Commission on Radiological Protection (ICRP).
      Translocation from one compartment to the next is taken to be governed by first
      order kinetics, which is formulated by the first-order differential equations. In
      the source program of this code, the conservation equations are solved for the
      mass balance that describes the transfer of a radionuclide between compartments.
      This code is applicable to the evaluation of the radioactivity of nuclides in an
      organ or tissue without modification of the source program. It is also possible
      to handle easily the cases of the revision of the biokinetic model or the
      application of a uniquely defined model by a user, because this code is designed
      so that all information on the biokinetic model structure is imported from an
      input file. The sample calculations are performed with the ICRP model, and the
      results are compared with the analytic solutions using simple models. It is
      suggested that this code provides sufficient result for the dose estimation and
      interpretation of monitoring data. 

PMID- 25061132
TI  - Intense foreshocks and a slow slip event preceded the 2014 Iquique Mw 8.1
      earthquake.
AB  - The subduction zone in northern Chile is a well-identified seismic gap that last
      ruptured in 1877. The moment magnitude (Mw) 8.1 Iquique earthquake of 1 April
      2014 broke a highly coupled portion of this gap. To understand the seismicity
      preceding this event, we studied the location and mechanisms of the foreshocks
      and computed Global Positioning System (GPS) time series at stations located on
      shore. Seismicity off the coast of Iquique started to increase in January 2014.
      After 16 March, several Mw > 6 events occurred near the low-coupled zone. These
      events migrated northward for ~50 kilometers until the 1 April earthquake
      occurred. On 16 March, on-shore continuous GPS stations detected a westward
      motion that we model as a slow slip event situated in the same area where the
      mainshock occurred. 

PMID- 25061130
TI  - Specific features of the influence of high-energy electron beams on the
      luminescent properties of undoped and Nb, Fe-doped Al2O3 crystals.
AB  - The influence of 10 MeV high-current electron beams accelerated by the M-30
      microtron on the luminescent properties of the alpha-Al2O3, Al2O3:Nb and Al2O3:Fe
      crystals has been studied. The effect of the long-term phosphorescence at room
      temperature has been found that can be used to monitor electron and gamma
      accelerator beams.

PMID- 25061133
TI  - Self-assembly of magnetite nanocubes into helical superstructures.
AB  - Organizing inorganic nanocrystals into complex architectures is challenging and
      typically relies on preexisting templates, such as properly folded DNA or
      polypeptide chains. We found that under carefully controlled conditions, cubic
      nanocrystals of magnetite self-assemble into arrays of helical superstructures in
      a template-free manner with >99% yield. Computer simulations revealed that the
      formation of helices is determined by the interplay of van der Waals and magnetic
      dipole-dipole interactions, Zeeman coupling, and entropic forces and can be
      attributed to spontaneous formation of chiral nanocube clusters. Neighboring
      helices within their densely packed ensembles tended to adopt the same handedness
      in order to maximize packing, thus revealing a novel mechanism of symmetry
      breaking and chirality amplification. 

PMID- 25061136
TI  - Weight-loss intervention by telephone: lessons learned.

PMID- 25061135
TI  - NIDDK international conference report on diabetes and depression: current
      understanding and future directions.
AB  - Comorbid diabetes and depression are a major clinical challenge as the outcomes
      of each condition are worsened by the other. This article is based on the
      presentations and discussions during an international meeting on diabetes and
      depression convened by the National Institute of Diabetes and Digestive and
      Kidney Diseases (NIDDK) in collaboration with the National Institute of Mental
      Health and the Dialogue on Diabetes and Depression. While the psychological
      burden of diabetes may contribute to depression in some cases, this explanation
      does not sufficiently explain the relationship between these two conditions.
      Shared biological and behavioral mechanisms, such as hypothalamic-pituitary
      adrenal axis activation, inflammation, autonomic dysfunction, sleep disturbance,
      inactive lifestyle, poor dietary habits, and environmental and cultural risk
      factors, are important to consider in understanding the link between depression
      and diabetes. Both individual psychological and pharmacological depression
      treatments are effective in people with diabetes, but the current range of
      treatment options is limited and has shown mixed effects on glycemic outcomes.
      More research is needed to understand what factors contribute to individual
      differences in vulnerability, treatment response, and resilience to depression
      and metabolic disorders across the life course and how best to provide care for
      people with comorbid diabetes and depression in different health care settings.
      Training programs are needed to create a cross-disciplinary workforce that can
      work in different models of care for comorbid conditions. 

PMID- 25061137
TI  - A new era in understanding diabetes disparities among U.S. Latinos--all are not
      equal.

PMID- 25061138
TI  - Prevalence of diabetes among Hispanics/Latinos from diverse backgrounds: the
      Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
AB  - OBJECTIVE: We examine differences in prevalence of diabetes and rates of
      awareness and control among adults from diverse Hispanic/Latino backgrounds in
      the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). RESEARCH DESIGN
      AND METHODS: The HCHS/SOL, a prospective, multicenter, population-based study,
      enrolled from four U.S. metropolitan areas from 2008 to 2011 16,415 18-74-year
      old people of Hispanic/Latino descent. Diabetes was defined by either fasting
      plasma glucose, impaired glucose tolerance 2 h after a glucose load, glycosylated
      hemoglobin (A1C), or documented use of hypoglycemic agents (scanned medications).
      RESULTS: Diabetes prevalence varied from 10.2% in South Americans and 13.4% in
      Cubans to 17.7% in Central Americans, 18.0% in Dominicans and Puerto Ricans, and
      18.3% in Mexicans (P < 0.0001). Prevalence related positively to age (P <
      0.0001), BMI (P < 0.0001), and years living in the U.S. (P = 0.0010) but was
      negatively related to education (P = 0.0005) and household income (P = 0.0043).
      Rate of diabetes awareness was 58.7%, adequate glycemic control (A1C <7%, 53
      mmol/mol) was 48.0%, and having health insurance among those with diabetes was
      52.4%. CONCLUSIONS: Present findings indicate a high prevalence of diabetes but
      considerable diversity as a function of Hispanic background. The low rates of
      diabetes awareness, diabetes control, and health insurance in conjunction with
      the negative associations between diabetes prevalence and both household income
      and education among Hispanics/Latinos in the U.S. have important implications for
      public health policies.

PMID- 25061140
TI  - Leukocyte profiles differ between type 1 and type 2 diabetes and are associated
      with metabolic phenotypes: results from the German Diabetes Study (GDS).
AB  - OBJECTIVE: Altered immune reactivity precedes and accompanies type 1 and type 2
      diabetes. We hypothesized that the metabolic phenotype relates to the systemic
      cellular immune status. RESEARCH DESIGN AND METHODS: A total of 194 metabolically
      well-controlled patients with type 1 diabetes (n = 62, mean diabetes duration
      1.29 years) or type 2 diabetes (n = 132, 1.98 years) and 60 normoglycemic persons
      underwent blood sampling for automated white blood cell counting (WBC) and flow
      cytometry. Whole-body insulin sensitivity was measured with hyperinsulinemic
      euglycemic clamp tests. RESULTS: Patients with type 2 diabetes had higher WBC
      counts than control subjects along with a higher percentage of T cells and
      activated T helper (Th) and cytotoxic T (Tc) cells but lower proportions of
      natural killer (NK) cells. In type 1 diabetes, the percentage of activated Th and
      Tc cells was also higher compared with control subjects, whereas the ratio of
      regulatory T (Treg) cells to activated Th cells was lower, suggesting diminished
      regulatory capacity. Parameters of glycemic control related positively to Treg
      cells only in type 2 diabetes. Upon age, sex, and body mass adjustments, insulin
      sensitivity correlated positively with monocytes, while circulating lipids
      correlated positively with T cell subsets in type 1 diabetes. CONCLUSIONS: Immune
      cell phenotypes showed distinct frequencies of occurrence in both diabetes types
      and associate with insulin sensitivity, glycemia, and lipidemia.

PMID- 25061139
TI  - Job strain as a risk factor for type 2 diabetes: a pooled analysis of 124,808 men
      and women.
AB  - OBJECTIVE: The status of psychosocial stress at work as a risk factor for type 2
      diabetes is unclear because existing evidence is based on small studies and is
      subject to confounding by lifestyle factors, such as obesity and physical
      inactivity. This collaborative study examined whether stress at work, defined as
      "job strain," is associated with incident type 2 diabetes independent of
      lifestyle factors. RESEARCH DESIGN AND METHODS: We extracted individual-level
      data for 124,808 diabetes-free adults from 13 European cohort studies
      participating in the IPD-Work Consortium. We measured job strain with baseline
      questionnaires. Incident type 2 diabetes at follow-up was ascertained using
      national health registers, clinical screening, and self-reports. We analyzed data
      for each study using Cox regression and pooled the study-specific estimates in
      fixed-effect meta-analyses. RESULTS: There were 3,703 cases of incident diabetes
      during a mean follow-up of 10.3 years. After adjustment for age, sex, and
      socioeconomic status (SES), the hazard ratio (HR) for job strain compared with no
      job strain was 1.15 (95% CI 1.06-1.25) with no difference between men and women
      (1.19 [1.06-1.34] and 1.13 [1.00-1.28], respectively). In stratified analyses,
      job strain was associated with an increased risk of diabetes among those with
      healthy and unhealthy lifestyle habits. In a multivariable model adjusted for
      age, sex, SES, and lifestyle habits, the HR was 1.11 (1.00-1.23). CONCLUSIONS:
      Findings from a large pan-European dataset suggest that job strain is a risk
      factor for type 2 diabetes in men and women independent of lifestyle factors.

PMID- 25061141
TI  - Prevalence of metabolic syndrome among Hispanics/Latinos of diverse background:
      the Hispanic Community Health Study/Study of Latinos.
AB  - OBJECTIVE: Approximately one-third of the adult U.S. population has the metabolic
      syndrome. Its prevalence is the highest among Hispanic adults, but variation by
      Hispanic/Latino background is unknown. Our objective was to quantify the
      prevalence of the metabolic syndrome among men and women 18-74 years of age of
      diverse Hispanic/Latino background. RESEARCH DESIGN AND METHODS: Two-stage area
      probability sample of households in four U.S. locales, yielding 16,319 adults
      (52% women) who self-identified as Cuban, Dominican, Mexican, Puerto Rican,
      Central American, or South American. The metabolic syndrome was defined according
      to the American Heart Association/National Heart, Lung, and Blood Institute 2009
      Joint Scientific Statement. The main outcome measures were age-standardized
      prevalence of the metabolic syndrome per the harmonized American Heart
      Association/National Heart, Lung, and Blood Institute definition and its
      component abnormalities. RESULTS: The metabolic syndrome was present in 36% of
      women and 34% of men. Differences in the age-standardized prevalence were seen by
      age, sex, and Hispanic/Latino background. The prevalence of the metabolic
      syndrome among those 18-44, 45-64, and 65-74 years of age was 23%, 50%, and 62%,
      respectively, among women; and 25%, 43%, and 55%, respectively, among men. Among
      women, the metabolic syndrome prevalence ranged from 27% in South Americans to
      41% in Puerto Ricans. Among men, prevalences ranged from 27% in South Americans
      to 35% in Cubans. In those with the metabolic syndrome, abdominal obesity was
      present in 96% of the women compared with 73% of the men; more men (73%) than
      women (62%) had hyperglycemia. CONCLUSIONS: The burden of cardiometabolic
      abnormalities is high in Hispanic/Latinos but varies by age, sex, and
      Hispanic/Latino background. Hispanics/Latinos are thus at increased, but
      modifiable, predicted lifetime risk of diabetes and its cardiovascular sequelae.

PMID- 25061142
TI  - Physical activity at altitude: challenges for people with diabetes: a review.
AB  - BACKGROUND: A growing number of subjects with diabetes take part in physical
      activities at altitude such as skiing, climbing, and trekking. Exercise under
      conditions of hypobaric hypoxia poses some unique challenges on subjects with
      diabetes, and the presence of diabetes can complicate safe and successful
      participation in mountain activities. Among others, altitude can alter
      glucoregulation. Furthermore, cold temperatures and altitude can complicate
      accurate reading of glucose monitoring equipment and storage of insulin. These
      factors potentially lead to dangerous hyperglycemia or hypoglycemia. Over the
      last years, more information has become available on this subject. PURPOSE: To
      provide an up-to-date overview of the pathophysiological changes during physical
      activity at altitude and the potential problems related to diabetes, including
      the use of (continuous) blood glucose monitors and insulin pumps. To propose
      practical recommendations for preparations and travel to altitude for subjects
      with diabetes. DATA SOURCES AND SYNTHESIS: We researched PubMed, medical
      textbooks, and related Internet sites, and extracted human studies and data based
      on relevance for diabetes, exercise, and altitude. LIMITATIONS: Given the paucity
      of controlled trials regarding diabetes and altitude, we composed a narrative
      review and filled in areas lacking diabetes-specific studies with data obtained
      from nondiabetic subjects. CONCLUSIONS: Subjects with diabetes can take part in
      activities at high, and even extreme, altitude. However, careful assessment of
      diabetes-related complications, optimal preparation, and adequate knowledge of
      glycemic regulation at altitude and altitude-related complications is needed.

PMID- 25061144
TI  - Virtual Look AHEAD program: initial support for a partly virtualized intensive
      lifestyle intervention in type 2 diabetes.

PMID- 25061145
TI  - Amelioration of cardiac morphology and function in type 1 diabetic patients with
      sustained success of pancreas transplant alone.

PMID- 25061146
TI  - Bariatric surgery induces weight loss but does not improve glycemic control in
      patients with type 1 diabetes.

PMID- 25061147
TI  - Resistance and aerobic exercise among adults with diabetes in the U.S.

PMID- 25061148
TI  - GLP-1 provoked severe hypoglycemia in an individual with type 2 diabetes and a
      benign insulinoma.

PMID- 25061149
TI  - Efficacy of the Telemedicine for Reach, Education, Access, and Treatment (TREAT)
      model for diabetes care.

PMID- 25061150
TI  - No sign of proliferative retinopathy in 15 patients with permanent neonatal
      diabetes with a median diabetes duration of 24 years.

PMID- 25061151
TI  - Comment on Home et al. Predictive and explanatory factors of change in HbA1c in a
      24-week observational study of 66,726 people with type 2 diabetes starting
      insulin analogs. Diabetes Care 2014;37:1237-1245.

PMID- 25061152
TI  - Response to comment on Home et al. Predictive and explanatory factors of change
      in HbA1c in a 24-week observational study of 66,726 people with type 2 diabetes
      starting insulin analogs. Diabetes Care 2014;37:1237-1245.

PMID- 25061153
TI  - Comment on Kahn and Davidson. The reality of type 2 diabetes prevention. Diabetes
      care 2014;37:943-949.

PMID- 25061154
TI  - Response to comment on Kahn and Davidson. The reality of type 2 diabetes
      prevention. Diabetes care 2014;37:943-949.

PMID- 25061155
TI  - Comment on Kahn and Sievenpiper. Dietary sugar and body weight: have we reached a
      crisis in the epidemic of obesity and diabetes? We have, but the pox on sugar is
      overwrought and overworked. Diabetes care 2014;37:957-962.

PMID- 25061156
TI  - Response to comment on Kahn and Sievenpiper. Dietary sugar and body weight: have
      we reached a crisis in the epidemic of obesity and diabetes? We have, but the pox
      on sugar is overwrought and overworked. Diabetes care 2014;37:957-962.

PMID- 25061157
TI  - Comment on Underwood et al. Preoperative A1C and clinical outcomes in patients
      with diabetes undergoing major noncardiac surgical procedures. Diabetes Care
      2014;37:611-616.

PMID- 25061158
TI  - Response to comment on Underwood et al. Preoperative A1C and clinical outcomes in
      patients with diabetes undergoing major noncardiac surgical procedures. Diabetes
      Care 2014;37:611-616.

PMID- 25061159
TI  - Lost in centrifugation: accounting for transporter protein losses in quantitative
      targeted absolute proteomics.
AB  - In drug development, considerable efforts are made to extrapolate from in vitro
      and preclinical findings to predict human drug disposition by using in vitro-in
      vivo extrapolation (IVIVE) approaches. Use of IVIVE strategies linked with
      physiologically based pharmacokinetic (PBPK) modeling is widespread, and
      regulatory agencies are accepting and occasionally requesting model analysis to
      support licensing submissions. Recently, there has been a drive to improve PBPK
      models by characterizing the absolute abundance of enzymes, transporters, and
      receptors within mammalian tissues and in vitro experimental systems using
      quantitative targeted absolute proteomics (QTAP). The absolute abundance of
      proteins relevant to processes governing drug disposition provided by QTAP will
      enable IVIVE-PBPK to incorporate terms for the abundance of enzymes and
      transporters in target populations. However, most studies that report absolute
      abundances of enzymes and transporter proteins do so in enriched membrane
      fractions so as to increase the abundance per sample, and thus the assay's
      sensitivity, rather than measuring the expected lower abundance in the more
      biologically meaningful whole cells or tissues. This communication discusses the
      balance between protein enrichment and potential loss during the preparation of
      membrane fractions from whole cells or tissues. Accounting for losses with
      recovery factors throughout the fractionation procedure provides a means to
      correct for procedural losses, thereby enabling the scaling of protein abundance
      from subcellular fractions to whole-cell or organ abundances. PBPK models based
      on corrected abundances will more closely resemble biological systems and
      facilitate development of more meaningful IVIVE scaling factors, producing more
      accurate quantitative predictions of drug disposition. 

PMID- 25061160
TI  - Microbial metabolites of omeprazole activate murine aryl hydrocarbon receptor in
      vitro and in vivo.
AB  - Omeprazole (OME), a proton pump inhibitor used to treat gastritis, is also an
      aryl hydrocarbon receptor (AhR) activator. OME activates AhR in human hepatocytes
      and hepatoma cells, but not in mice in vivo or in vitro. We recently discovered
      that this species-specific difference results from a difference in a few amino
      acids in the ligand-binding domain of AhR. However, OME activates both mouse and
      human AhRs in the yeast reporter assay system. Nevertheless, the cause of this
      discrepancy in OME responses remains unknown. Here, we report that CYP1A1 mRNA
      expression in mouse cecum was elevated after OME administration, although the
      mouse is regarded as an OME-unresponsive animal. Using the yeast reporter assay
      system with human and murine AhRs, we found AhR agonist-like activity in the
      cecal extracts of OME-treated mice. We speculated that OME metabolites produced
      by cecal bacteria might activate murine AhRs in vivo. In high-performance liquid
      chromatography (HPLC) analysis, AhR agonist-like activity of cecal bacterial
      culture and cecal extracts were detected at the same retention time. AhR agonist
      like activity was also detected in the HPLC fractions of yeast culture media
      containing OME. This unknown substance could induce reporter gene expression via
      mouse and human AhRs. The agonist-like activity of the OME metabolite was reduced
      by concomitant alpha-naphthoflavone exposure. These results indicate that a yeast
      generated OME metabolite elicited the response of mouse AhR to OME in the yeast
      system, and that bacterial OME metabolites may act as AhR ligands in human and
      mouse intestines. 

PMID- 25061161
TI  - Assessment of intestinal availability (FG) of substrate drugs of cytochrome p450s
      by analyzing changes in pharmacokinetic properties caused by drug-drug
      interactions.
AB  - In this study, we developed the drug-drug interaction (DDI) method as a new
      assessment technique of intestinal availability (F(G), the fraction of drug
      transferred from the intestinal enterocytes into the liver, escaping from
      intestinal metabolism) based on the clearance theory. This method evaluates F(G)
      from changes caused by DDIs in the area under the blood concentration-time curve
      and in the elimination half-life of victim drugs. Application of the DDI method
      to data from the literature revealed that the mean and S.D. of F(G) values for 20
      substrate drugs of CYP3A was 0.56 +/- 0.29, whereas that for 8 substrate drugs of
      CYP2C9, CYP2C19, and CYP2D6 was 0.86 +/- 0.11. These results were consistent with
      the fact that intestinal metabolism is mediated predominantly by CYP3A. The DDI
      method showed reasonable correlations with the conventional i.v./p.o. method and
      the grape fruit juice (GFJ) method (coefficients of determination of 0.41 and
      0.81, respectively). The i.v./p.o. method was more susceptible to fluctuations in
      the hepatic blood flow rate compared with the DDI and GFJ methods. The DDI method
      evaluates F(G) separating from the absorption ratio (F(A)) although it requires
      approximation of F(A). Since preciseness of approximation of F(A) does not
      greatly affect the evaluation of F(G) by the DDI method, we proposed a reasonable
      approximation method of F(A) for the evaluation of F(G) in the DDI method. The
      DDI method would be applicable to a broad range of situations in which various
      DDI data are utilizable.

PMID- 25061162
TI  - Pharmacoproteomics-based reconstruction of in vivo P-glycoprotein function at
      blood-brain barrier and brain distribution of substrate verapamil in
      pentylenetetrazole-kindled epilepsy, spontaneous epilepsy, and phenytoin
      treatment models.
AB  - The purpose of this study was to demonstrate experimentally that alterations of
      in vivo transporter function at the blood-brain barrier (BBB) in disease and
      during pharmacotherapy can be reconstructed from in vitro data based on our
      established pharmacoproteomic concept of reconstructing in vivo function by
      integrating intrinsic transport activity per transporter molecule and absolute
      protein expression level at the BBB. Pentylenetetrazole (PTZ)-kindled and
      spontaneous model of epilepsy (EL) mice were used as models of chemically induced
      and spontaneous epilepsy, respectively. A mouse model of antiepileptic drug
      treatment was prepared by consecutive 5-week administration of phenytoin (PHT).
      Quantitative targeted absolute proteomic analysis of 31 membrane proteins showed
      that P-glycoprotein (P-gp/mdr1a) protein expression levels were significantly
      increased in brain capillaries of PTZ (129%), EL (143%), and PHT mice (192%)
      compared with controls. The brain-to-plasma concentration ratios (Kp brain) of P
      gp/mdr1a substrate verapamil were 0.563, 0.394, 0.432, and 0.234 in control, PTZ,
      EL, and PHT mice, respectively. In vivo P-gp/mdr1a function at the BBB was
      reconstructed from the measured P-gp/mdr1a protein expression levels and
      intrinsic transport activity for verapamil per P-gp/mdr1a previously reported by
      our group. Then, the reconstructed P-gp/mdr1a functional activities were
      integrated with unbound fractions of verapamil in plasma and brain to reconstruct
      Kp brain of verapamil. In all mice, reconstructed Kp brain values agreed well
      with the observed values within a 1.21-fold range. These results demonstrate that
      altered P-gp functions at the BBB in epilepsy and during pharmacotherapy can be
      reconstructed from in vitro data by means of our pharmacoproteomic approach. 

PMID- 25061163
TI  - TIF-90 tips the balance in rRNA synthesis.

PMID- 25061164
TI  - Carfilzomib: a new opportunity for WM patients.

PMID- 25061165
TI  - Molecular response in CML: where is the bar?

PMID- 25061166
TI  - HSCs and niche relations marked by CD166.

PMID- 25061167
TI  - Writing guidelines without a net: ECD.

PMID- 25061168
TI  - Erythroid mRNA processing: a "splice of life".

PMID- 25061169
TI  - Platelets as pivot in the antiphospholipid syndrome.

PMID- 25061170
TI  - Big bang theory of stem-like T cells confirmed.

PMID- 25061171
TI  - Prediction of IVIG treatment efficiency in fetal/neonatal alloimmune
      thrombocytopenia.

PMID- 25061172
TI  - Identification of ITK deficiency as a novel genetic cause of idiopathic CD4+ T
      cell lymphopenia.

PMID- 25061173
TI  - Myeloma cell sensitivity to bortezomib is associated with Dicer1 expression.

PMID- 25061174
TI  - Imaging flow cytometry documents incomplete resistance of human sickle F-cells to
      ex vivo hypoxia-induced sickling.

PMID- 25061175
TI  - Misleading results from saliva samples of patients post-BMT in exome analyses.

PMID- 25061176
TI  - The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma.
AB  - Glycosylation is a stepwise procedure of covalent attachment of oligosaccharide
      chains to proteins or lipids, and alterations in this process, especially
      increased sialylation, have been associated with malignant transformation and
      metastasis. The role of altered sialylation in multiple myeloma (MM) cell
      trafficking has not been previously investigated. In the present study we
      identified high expression of beta-galactoside alpha-2,3-sialyltransferase,
      ST3GAL6, in MM cell lines and patients. This gene plays a key role in selectin
      ligand synthesis in humans through the generation of functional sialyl Lewis X.
      In MRC IX patients, high expression of this gene is associated with inferior
      overall survival. In this study we demonstrate that knockdown of ST3GAL6 results
      in a significant reduction in levels of alpha-2,3-linked sialic acid on the
      surface of MM cells with an associated significant reduction in adhesion to MM
      bone marrow stromal cells and fibronectin along with reduced transendothelial
      migration in vitro. In support of our in vitro findings, we demonstrate
      significantly reduced homing and engraftment of ST3GAL6 knockdown MM cells to the
      bone marrow niche in vivo, along with decreased tumor burden and prolonged
      survival. This study points to the importance of altered glycosylation,
      particularly sialylation, in MM cell adhesion and migration. 

PMID- 25061177
TI  - A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG
      gene.
AB  - Macrothrombocytopenias are the most important subgroup of inherited
      thrombocytopenias. This subgroup is particularly heterogeneous because the
      affected genes are involved in various functions such as cell signaling,
      cytoskeleton organization, and gene expression. Herein we describe the clinical
      and hematological features of a consanguineous family with a severe autosomal
      recessive macrothrombocytopenia associated with a thrombocytopathy inducing a
      bleeding tendency in the homozygous mutated patients. Platelet activation and
      cytoskeleton reorganization were impaired in these homozygous patients. Exome
      sequencing identified a c.222C>G mutation (missense p.74Ile>Met) in PRKACG, a
      gene encoding the gamma-catalytic subunit of the cyclic adenosine monophosphate
      dependent protein kinase, the mutated allele cosegregating with the
      macrothrombocytopenia. We demonstrate that the p.74Ile>Met PRKACG mutation is
      associated with a marked defect in proplatelet formation and a low level in
      filamin A in megakaryocytes (MKs). The defect in proplatelet formation was
      rescued in vitro by lentiviral vector-mediated overexpression of wild-type PRKACG
      in patient MKs. We thus conclude that PRKACG is a new central actor in platelet
      biogenesis and a new gene involved in inherited thrombocytopenia with giant
      platelets associated with a thrombocytopathy. 

PMID- 25061179
TI  - Ghosts from the past.

PMID- 25061181
TI  - Infectious diseases. Ebola drugs still stuck in lab.

PMID- 25061178
TI  - CYR61/CCN1 overexpression in the myeloma microenvironment is associated with
      superior survival and reduced bone disease.
AB  - Secreted protein CCN1, encoded by CYR61, is involved in wound healing,
      angiogenesis, and osteoblast differentiation. We identified CCN1 as a
      microenvironmental factor produced by mesenchymal cells and overexpressed in
      bones of a subset of patients with monoclonal gammopathy of undetermined
      significance (MGUS), asymptomatic myeloma (AMM), and multiple myeloma (MM). Our
      analysis showed that overexpression of CYR61 was independently associated with
      superior overall survival of MM patients enrolled in our Total Therapy 3
      protocol. Moreover, elevated CCN1 was associated with a longer time for MGUS/AMM
      to progress to overt MM. During remission from MM, high levels of CCN1 were
      associated with superior progression-free and overall survival and stratified
      patients with molecularly defined high-risk MM. Recombinant CCN1 directly
      inhibited in vitro growth of MM cells, and overexpression of CYR61 in MM cells
      reduced tumor growth and prevented bone destruction in vivo in severe combined
      immunodeficiency-hu mice. Signaling through alphavbeta3 was required for CCN1
      prevention of bone disease. CYR61 expression may signify early perturbation of
      the microenvironment before conversion to overt MM and may be a compensatory
      mechanism to control MM progression. Therapeutics that upregulate CYR61 should be
      investigated for treating MM bone disease. 

PMID- 25061182
TI  - Planetary science. Road hazards threaten rover.

PMID- 25061183
TI  - Funding. NIH institute considers broad shift to 'people' awards.

PMID- 25061184
TI  - Tropical diseases. Dengue vaccine trial poses public health quandary.

PMID- 25061185
TI  - Energy policy. Oil sands fight heats up in U.S.

PMID- 25061186
TI  - Fusion's restless pioneers.

PMID- 25061187
TI  - Conservation policy. Wildlife decline and social conflict.

PMID- 25061188
TI  - Molecular biology. Ribosome rescue and neurodegeneration.

PMID- 25061189
TI  - Biophysics. Ultraslow relaxation of confined DNA.

PMID- 25061190
TI  - Catalysis. Self-control tames the coupling of reactive radicals.

PMID- 25061191
TI  - Ecology. Why are plant-pollinator networks nested?

PMID- 25061192
TI  - Metamaterials. A cloaking coating for murky media.

PMID- 25061193
TI  - Neuroscience. Astrocytes eyeball axonal mitochondria.

PMID- 25061194
TI  - In defense of fences.

PMID- 25061195
TI  - In defense of fences--response.

PMID- 25061196
TI  - Early Americans: misstated results.

PMID- 25061197
TI  - Early Americans: respecting ancestors.

PMID- 25061198
TI  - Early Americans: respecting ancestors--response.

PMID- 25061199
TI  - Vanishing fauna. Introduction.

PMID- 25061200
TI  - The empty forest.

PMID- 25061201
TI  - An animal-rich future.

PMID- 25061202
TI  - Defaunation in the Anthropocene.
AB  - We live amid a global wave of anthropogenically driven biodiversity loss: species
      and population extirpations and, critically, declines in local species abundance.
      Particularly, human impacts on animal biodiversity are an under-recognized form
      of global environmental change. Among terrestrial vertebrates, 322 species have
      become extinct since 1500, and populations of the remaining species show 25%
      average decline in abundance. Invertebrate patterns are equally dire: 67% of
      monitored populations show 45% mean abundance decline. Such animal declines will
      cascade onto ecosystem functioning and human well-being. Much remains unknown
      about this "Anthropocene defaunation"; these knowledge gaps hinder our capacity
      to predict and limit defaunation impacts. Clearly, however, defaunation is both a
      pervasive component of the planet's sixth mass extinction and also a major driver
      of global ecological change. 

PMID- 25061203
TI  - Reversing defaunation: restoring species in a changing world.
AB  - The rate of biodiversity loss is not slowing despite global commitments, and the
      depletion of animal species can reduce the stability of ecological communities.
      Despite this continued loss, some substantial progress in reversing defaunation
      is being achieved through the intentional movement of animals to restore
      populations. We review the full spectrum of conservation translocations, from
      reinforcement and reintroduction to controversial conservation introductions that
      seek to restore populations outside their indigenous range or to introduce
      ecological replacements for extinct forms. We place the popular, but
      misunderstood, concept of rewilding within this framework and consider the future
      role of new technical developments such as de-extinction. 

PMID- 25061204
TI  - Ultrafast optics. Ultrafast optical control by few photons in engineered fiber.
AB  - Fast control of a strong optical beam by a few photons is an outstanding
      challenge that limits the performance of quantum sensors and optical processing
      devices. We report that a fast and efficient optical gate can be realized in an
      optical fiber that has been engineered with molecular-scale accuracy. Highly
      efficient, distributed phase-matched photon-photon interaction was achieved in
      the fiber with locally controlled, nanometer-scale core variations. A three
      photon input was used to manipulate a Watt-scale beam at a speed exceeding 500
      gigahertz. In addition to very fast beam control, the results provide a path to
      developing a new class of sensitive receivers capable of operating at very high
      rates. 

PMID- 25061205
TI  - Quantum computing. Defining and detecting quantum speedup.
AB  - The development of small-scale quantum devices raises the question of how to
      fairly assess and detect quantum speedup. Here, we show how to define and measure
      quantum speedup and how to avoid pitfalls that might mask or fake such a speedup.
      We illustrate our discussion with data from tests run on a D-Wave Two device with
      up to 503 qubits. By using random spin glass instances as a benchmark, we found
      no evidence of quantum speedup when the entire data set is considered and
      obtained inconclusive results when comparing subsets of instances on an instance
      by-instance basis. Our results do not rule out the possibility of speedup for
      other classes of problems and illustrate the subtle nature of the quantum speedup
      question. 

PMID- 25061206
TI  - Quantum metrology. Fisher information and entanglement of non-Gaussian spin
      states.
AB  - Entanglement is the key quantum resource for improving measurement sensitivity
      beyond classical limits. However, the production of entanglement in mesoscopic
      atomic systems has been limited to squeezed states, described by Gaussian
      statistics. Here, we report on the creation and characterization of non-Gaussian
      many-body entangled states. We develop a general method to extract the Fisher
      information, which reveals that the quantum dynamics of a classically unstable
      system creates quantum states that are not spin squeezed but nevertheless
      entangled. The extracted Fisher information quantifies metrologically useful
      entanglement, which we confirm by Bayesian phase estimation with sub-shot-noise
      sensitivity. These methods are scalable to large particle numbers and applicable
      directly to other quantum systems. 

PMID- 25061207
TI  - Quantum simulation. Coherent imaging spectroscopy of a quantum many-body spin
      system.
AB  - Quantum simulators, in which well-controlled quantum systems are used to
      reproduce the dynamics of less understood ones, have the potential to explore
      physics inaccessible to modeling with classical computers. However, checking the
      results of such simulations also becomes classically intractable as system sizes
      increase. Here, we introduce and implement a coherent imaging spectroscopic
      technique, akin to magnetic resonance imaging, to validate a quantum simulation.
      We use this method to determine the energy levels and interaction strengths of a
      fully connected quantum many-body system. Additionally, we directly measure the
      critical energy gap near a quantum phase transition. We expect this general
      technique to become a verification tool for quantum simulators once experiments
      advance beyond proof-of-principle demonstrations and exceed the resources of
      conventional computers. 

PMID- 25061208
TI  - Paleoclimate. Synchronization of North Pacific and Greenland climates preceded
      abrupt deglacial warming.
AB  - Some proposed mechanisms for transmission of major climate change events between
      the North Pacific and North Atlantic predict opposing patterns of variations;
      others suggest synchronization. Resolving this conflict has implications for
      regulation of poleward heat transport and global climate change. New multidecadal
      resolution foraminiferal oxygen isotope records from the Gulf of Alaska (GOA)
      reveal sudden shifts between intervals of synchroneity and asynchroneity with the
      North Greenland Ice Core Project (NGRIP) delta(18)O record over the past 18,000
      years. Synchronization of these regions occurred 15,500 to 11,000 years ago, just
      prior to and throughout the most abrupt climate transitions of the last 20,000
      years, suggesting that dynamic coupling of North Pacific and North Atlantic
      climates may lead to critical transitions in Earth's climate system. 

PMID- 25061209
TI  - Dinosaur evolution. A Jurassic ornithischian dinosaur from Siberia with both
      feathers and scales.
AB  - Middle Jurassic to Early Cretaceous deposits from northeastern China have yielded
      varied theropod dinosaurs bearing feathers. Filamentous integumentary structures
      have also been described in ornithischian dinosaurs, but whether these filaments
      can be regarded as part of the evolutionary lineage toward feathers remains
      controversial. Here we describe a new basal neornithischian dinosaur from the
      Jurassic of Siberia with small scales around the distal hindlimb, larger
      imbricated scales around the tail, monofilaments around the head and the thorax,
      and more complex featherlike structures around the humerus, the femur, and the
      tibia. The discovery of these branched integumentary structures outside theropods
      suggests that featherlike structures coexisted with scales and were potentially
      widespread among the entire dinosaur clade; feathers may thus have been present
      in the earliest dinosaurs. 

PMID- 25061210
TI  - RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes
      neurodegeneration.
AB  - In higher eukaryotes, transfer RNAs (tRNAs) with the same anticodon are encoded
      by multiple nuclear genes, and little is known about how mutations in these genes
      affect translation and cellular homeostasis. Similarly, the surveillance systems
      that respond to such defects in higher eukaryotes are not clear. Here, we
      discover that loss of GTPBP2, a novel binding partner of the ribosome recycling
      protein Pelota, in mice with a mutation in a tRNA gene that is specifically
      expressed in the central nervous system causes ribosome stalling and widespread
      neurodegeneration. Our results not only define GTPBP2 as a ribosome rescue factor
      but also unmask the disease potential of mutations in nuclear-encoded tRNA genes.

PMID- 25061211
TI  - Clathrin adaptors. AP2 controls clathrin polymerization with a membrane-activated
      switch.
AB  - Clathrin-mediated endocytosis (CME) is vital for the internalization of most cell
      surface proteins. In CME, plasma membrane-binding clathrin adaptors recruit and
      polymerize clathrin to form clathrin-coated pits into which cargo is sorted.
      Assembly polypeptide 2 (AP2) is the most abundant adaptor and is pivotal to CME.
      Here, we determined a structure of AP2 that includes the clathrin-binding beta2
      hinge and developed an AP2-dependent budding assay. Our findings suggest that an
      autoinhibitory mechanism prevents clathrin recruitment by cytosolic AP2. A large
      scale conformational change driven by the plasma membrane phosphoinositide
      phosphatidylinositol 4,5-bisphosphate and cargo relieves this autoinhibition,
      triggering clathrin recruitment and hence clathrin-coated bud formation. This
      molecular switching mechanism can couple AP2's membrane recruitment to its key
      functions of cargo and clathrin binding. 

PMID- 25061212
TI  - Mechanism of actin filament pointed-end capping by tropomodulin.
AB  - Proteins that cap the ends of the actin filament are essential regulators of
      cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed
      end, tropomodulin (Tmod) is the only protein known to cap the slowly growing
      pointed end. The lack of structural information severely limits our understanding
      of Tmod's capping mechanism. We describe crystal structures of actin complexes
      with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal
      domains of Tmod. The structures and biochemical analysis of structure-inspired
      mutants showed that one Tmod molecule interacts with three actin subunits at the
      pointed end, while also contacting two tropomyosin molecules on each side of the
      filament. We found that Tmod achieves high-affinity binding through several
      discrete low-affinity interactions, which suggests a mechanism for controlled
      subunit exchange at the pointed end. 

PMID- 25061213
TI  - A scientific partnership.

PMID- 25061214
TI  - Ecological networks. On the structural stability of mutualistic systems.
AB  - In theoretical ecology, traditional studies based on dynamical stability and
      numerical simulations have not found a unified answer to the effect of network
      architecture on community persistence. Here, we introduce a mathematical
      framework based on the concept of structural stability to explain such a
      disparity of results. We investigated the range of conditions necessary for the
      stable coexistence of all species in mutualistic systems. We show that the
      apparently contradictory conclusions reached by previous studies arise as a
      consequence of overseeing either the necessary conditions for persistence or its
      dependence on model parameterization. We show that observed network architectures
      maximize the range of conditions for species coexistence. We discuss the
      applicability of structural stability to study other types of interspecific
      interactions. 

PMID- 25061215
TI  - Ex vivo lung perfusion in clinical lung transplantation--state of the art.
AB  - Ex vivo lung perfusion (EVLP) has emerged as a new technique for assessing and
      potentially reconditioning human donor lungs previously unacceptable for clinical
      transplantation with the potential to dramatically push the limits of organ
      acceptability. With the recent introduction of portable EVLP, a new era in lung
      preservation may be upon us with the opportunity to also limit organ ischaemic
      times and potentially improve the outcome of donor lungs already deemed
      acceptable for transplantation. It took over half a century for the technique to
      evolve from basic theory to semi-automated circuits fit for clinical use that are
      now rapidly being adopted in transplant centres across the globe. With this field
      in constant evolution and many unanswered questions remaining, our review serves
      as an update on the state of the art of EVLP in clinical lung transplantation. 

PMID- 25061216
TI  - Incidence and severity of primary graft dysfunction after lung transplantation
      using rejected grafts reconditioned with ex vivo lung perfusion.
AB  - OBJECTIVES: Ex vivo lung perfusion (EVLP) is a novel technique used to evaluate
      and recondition marginal or rejected grafts. Primary graft dysfunction (PGD) is a
      major early complication after lung transplantation (LTx). The use of marginal or
      initially rejected grafts may increase its incidence and severity. The aim of
      this study is to evaluate the incidence of PGD after LTx using rejected grafts
      reconditioned with EVLP. METHODS: PGD has been evaluated immediately after LTx
      (t0) and after 72 h (t72) in patients receiving standard (Group A) or
      reconditioned (Group B) grafts. EVLP was performed using a controlled acellular
      perfusion according to the Toronto technique. RESULTS: From July 2011 to February
      2013, 36 LTxs have been performed: 28 patients (21 M/7 F, mean age 51.7 +/- 14.7
      years) in Group A and 8 (6 M/2 F, mean age 46.6 +/- 9.8 years) in Group B
      (successful recondition rate of 73%, 8 of 11 cases). Incidence rate of PGD 3 at
      t0 and at t72 (Group A versus Group B) was 50 vs 37% (P = NS) and 25 vs 0% (P =
      NS), respectively. Post-transplant extracorporeal membrane oxygenation was
      required in 5 and 2 patients in Groups A and B, respectively (P = NS).
      CONCLUSIONS: The use of initially rejected grafts treated with EVLP does not
      increase the incidence and severity of PGD after LTx. Although comparison of PGD
      3 incidence in the two groups did not reach a statistical difference, all EVLP
      patients suffering from severe PGD early after transplant recovered normal lung
      function at 72 h, suggesting a protective role of EVLP against PGD occurrence and
      severity.

PMID- 25061217
TI  - Bioprinting technology and its applications.
AB  - Bioprinting technology has emerged as a powerful tool for building tissue and
      organ structures in the field of tissue engineering. This technology allows
      precise placement of cells, biomaterials and biomolecules in spatially predefined
      locations within confined three-dimensional (3D) structures. Various bioprinting
      technologies have been developed and utilized for applications in life sciences,
      ranging from studying cellular mechanisms to constructing tissues and organs for
      implantation, including heart valve, myocardial tissue, trachea and blood
      vessels. In this article, we introduce the general principles and limitations of
      the most widely used bioprinting technologies, including jetting- and extrusion
      based systems. Application-based research focused on tissue regeneration is
      presented, as well as the current challenges that hamper clinical utility of
      bioprinting technology. 

PMID- 25061218
TI  - Towards a better understanding of ex vivo lung perfusion.

PMID- 25061219
TI  - Lung transplantation from initially rejected donors after ex vivo lung
      reconditioning: the French experience.
AB  - OBJECTIVES: Only 15% of brain death donors are considered suitable for lung
      transplantation (LTx). The normothermic ex vivo lung perfusion technique is used
      to potentially increase the availability of high-risk lung donors. We report our
      experience of LTx with initially rejected donors after ex vivo lung
      reconditioning (EVLR). METHODS: From April 2011 to May 2013, we performed EVLR
      for 32 pairs of donor lungs deemed unsuitable for transplantation and rejected by
      the 11 French lung transplant teams. After EVLR, lungs with acceptable function
      were transplanted. During the same period, 81 double-lung transplantations (DLTx)
      were used as controls. RESULTS: During EVLR, 31 of 32 donor lungs recovered
      physiological function with a median PO2/FiO2 ratio increasing from 274 (range
      162-404) mmHg to 511 (378-668) mmHg at the end of EVLR (P < 0.0001). Thirty-one
      DLTx were performed. The incidence of primary graft dysfunction 72 h after LTx
      was 9.5% in the EVLR group and 8.5% in the control group (P = 1). The median time
      of extubation, intensive care unit and hospital lengths of stay were 1, 9 and 37
      days in the EVLR group and 1 (P = 0.17), 6 (P = 0.06) and 28 days (P = 0.09) in
      the control group, respectively. Thirty-day mortality rates were 3.3% (n = 1) in
      the EVLR group and 3.7% (n = 3) in the control group (P = 0.69). One-year
      survival rates were 93% in the EVLR group and 91% in the control group.
      CONCLUSIONS: EVLR is a reliable and repeatable technique that offers a
      significant increase of available donors. The results of LTx with EVLR lungs are
      similar to those obtained with conventional donors.

PMID- 25061220
TI  - Repair of unbalanced atrioventricular septal defect with small right ventricle.
AB  - A 2-month-old boy with trisomy 21, a small right ventricle, and an unbalanced
      atrioventricular septal defect underwent successful biventricular repair without
      atrial fenestration. We decided to perform leftward partitioning of the
      atrioventricular valve to widen the right ventricle inflow tract. This procedure
      increases the size of the right-sided valve and allows full function of the right
      ventricle without an atrial communication. This technique should be employed in
      patients with a small right ventricle and an unbalanced atrioventricular septal
      defect, as an alternative to atrial septal fenestration or univentricular
      palliation. 

PMID- 25061221
TI  - Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy.
AB  - BACKGROUND: Ongoing debate exists concerning the optimal choice and duration of
      antibiotic prophylaxis as well as the reasonable calculated empiric antibiotic
      therapy for hospital-acquired infections in critically ill cardiac surgery
      patients. METHODS: A nationwide questionnaire was distributed to all German heart
      surgery centers concerning antibiotic prophylaxis and the calculated empiric
      antibiotic therapy. RESULTS: The response to the questionnaire was 87.3%. All
      clinics that responded use antibiotic prophylaxis, 79% perform it not longer than
      24 h (single-shot: 23%; 2 doses: 29%; 3 doses: 27%; 4 doses: 13%; and >5 doses:
      8%). Cephalosporin was used in 89% of clinics (46% second-generation, 43% first
      generation cephalosporin). If sepsis is suspected, the following diagnostics are
      performed routinely: wound inspection 100%; white blood cell count 100%;
      radiography 99%; C-reactive protein 97%; microbiological testing of urine 91%,
      blood 81%, and bronchial secretion 81%; procalcitonin 74%; and echocardiography
      75%. The calculated empiric antibiotic therapy (depending on the suspected focus)
      consists of a multidrug combination with broad-spectrum agents. CONCLUSION: This
      survey shows that existing national guidelines and recommendations concerning
      perioperative antibiotic prophylaxis and calculated empiric antibiotic therapy
      are well applied in almost all German heart centers.

PMID- 25061222
TI  - Single-operator knot-tying by knot-pusher for minimally invasive cardiac surgery.
AB  - We describe a single-operator knot-tying technique using a knot-pusher for
      minimally invasive cardiac surgery. With this technique, the surgeon is able to
      control the tension on both suture ends in tightening knots without the aid of an
      assistant. 

PMID- 25061223
TI  - Adult-born granule cells mature through two functionally distinct states.
AB  - Adult-born granule cells (ABGCs) are involved in certain forms of hippocampus
      dependent learning and memory. It has been proposed that young but functionally
      integrated ABGCs (4-weeks-old) specifically contribute to pattern separation
      functions of the dentate gyrus due to their heightened excitability, whereas old
      ABGCs (>8 weeks old) lose these capabilities. Measuring multiple cellular and
      integrative characteristics of 3- 10-week-old individual ABGCs, we show that
      ABGCs consist of two functionally distinguishable populations showing highly
      distinct input integration properties (one group being highly sensitive to narrow
      input intensity ranges while the other group linearly reports input strength)
      that are largely independent of the cellular age and maturation stage, suggesting
      that 'classmate' cells (born during the same period) can contribute to the
      network with fundamentally different functions. Thus, ABGCs provide two
      temporally overlapping but functionally distinct neuronal cell populations,
      adding a novel level of complexity to our understanding of how life-long
      neurogenesis contributes to adult brain function.

PMID- 25061224
TI  - Traffic control: adaptor proteins guide dynein-cargo takeoff.

PMID- 25061225
TI  - "Father knows best?".

PMID- 25061226
TI  - Sox2, a marker for stem-like tumor cells in skin squamous cell carcinoma and
      hedgehog subgroup medulloblastoma.
AB  - Heterogeneity within tumors is becoming increasingly recognized as an important
      cause of treatment failure in cancer. Two recent studies use fate-mapping and
      limiting dilution transplantation assays to identify SRY (sex determining region
      Y)-box 2 (Sox2) as cancer stem-cell marker and driver of cancer stemness.

PMID- 25061227
TI  - Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein
      girdin.
AB  - In clathrin-mediated endocytosis (CME), specificity and selectivity for cargoes
      are thought to be tightly regulated by cargo-specific adaptors for distinct
      cellular functions. Here, we show that the actin-binding protein girdin is a
      regulator of cargo-selective CME. Girdin interacts with dynamin 2, a GTPase that
      excises endocytic vesicles from the plasma membrane, and functions as its GTPase
      activating protein. Interestingly, girdin depletion leads to the defect in
      clathrin-coated pit formation in the center of cells. Also, we find that girdin
      differentially interacts with some cargoes, which competitively prevents girdin
      from interacting with dynamin 2 and confers the cargo selectivity for CME.
      Therefore, girdin regulates transferrin and E-cadherin endocytosis in the center
      of cells and their subsequent polarized intracellular localization, but has no
      effect on integrin and epidermal growth factor receptor endocytosis that occurs
      at the cell periphery. Our results reveal that girdin regulates selective CME via
      a mechanism involving dynamin 2, but not by operating as a cargo-specific
      adaptor. 

PMID- 25061228
TI  - Incidence of sudden cardiac death in Germany: results from an emergency medical
      service registry in Lower Saxony.
AB  - AIMS: Sudden cardiac death (SCD) is among the most common causes of death in
      western countries including Germany. Whereas risk stratification and primary
      prevention is still insufficient, we also lack accurate incidence estimates.
      Current estimates vary widely (18.6-128/100,000/year), but data on SCD incidence
      in Germany are missing. Depending on SCD definitions, death needs to occur
      between 1 and 24 h after the onset of symptoms. METHODS AND RESULTS: In the
      district of Aurich (190,000 inhabitants, Lower Saxony, Germany), emergency
      medical service (EMS) is provided by a district government operated single
      carrier and two hospitals. To evaluate all EMS calls in this district from 2002
      to 2009, we obtained EMS protocols, medical records, and death certificates for
      data analysis and adjudication of SCD. We defined SCD according to the definition
      of the World Health Organization, considering patients with cardiac arrest within
      <=1 h after the onset of symptoms. We also required cardiopulmonary resuscitation
      being performed by EMS personnel. The overall mortality rate in the district of
      Aurich (1060/100,000/year) corresponded well with the average mortality rate in
      Germany (1030/100,000/year). During the observation period, we adjudicated 1212
      SCD cases, equivalent to an annual rate of 151 SCD cases (81 cases/100,000/year).
      Rates remained remarkably stable over time, and affected a considerable number of
      individuals of working age (32/100,000/year). CONCLUSION: Consistent with prior
      reports, the SCD incidence in a district of Germany is substantial. Despite an
      elaborate EMS system and advanced medical care, SCD rates remain stable and
      necessitate improved, individualized risk stratification.

PMID- 25061230
TI  - Birth year distribution in reported hepatitis C cases in Switzerland.
AB  - Data of the national hepatitis C virus (HCV) notification system and the Swiss
      hepatitis C cohort study have been analysed for birth year distribution. Persons
      born between 1955 and 1974 are disproportionally affected by HCV, accounting for
      61% of all reported infections. Over the course of the reporting period from 1988
      to 2012, the majority of affected persons were born in the mid-60s and a sharply
      increasing proportion between 1975 and 1984 (from 0.6 to 19.5%). To enhance the
      so far insufficient HCV detection rates in Switzerland, additional testing
      strategies such as birth cohort screening must be further evaluated and
      discussed. 

PMID- 25061229
TI  - Catheter ablation of atrial tachyarrhythmias causing inappropriate implantable
      cardioverter-defibrillator shocks.
AB  - AIMS: Inappropriate shocks have been an important issue post-implantable
      cardioverter-defibrillator (ICD) implantation. Moreover, inappropriate ICD shocks
      are associated with increased mortality. The objective of this study was to
      evaluate the feasibility of catheter ablation therapy for atrial tachyarrhythmias
      (ATa) responsible for inappropriate ICD shocks. METHODS AND RESULTS: Among 108
      consecutive patients who underwent ICD implantations, 22, 5, and 3 experienced
      inappropriate ICD shocks due to ATa, sinus tachycardia, and T-wave oversensing,
      respectively. Among the 22 patients with ATa, 18 patients (55 +/- 10 years, 15
      men, structural heart disease in 9) underwent catheter ablation of ATa causing
      inappropriate shocks. The median duration between the ICD implantation and first
      inappropriate shock was 10.0 (3.0-24.5) months. The ATa were atrial fibrillation
      (AF), atrial flutter (AFL), and atrioventricular nodal reentrant tachycardia in
      14, 2, and 2 patients, respectively. One patient underwent an atrioventricular
      nodal ablation for persistent AF associated with a venous anomaly. Among 13
      patients who underwent pulmonary vein antrum isolation, 10 (76.9%) were free from
      AF for a median of 21.0 (13-37.3) months after an average of 1.3 +/- 0.5
      procedures. In four patients with AFL or a supraventricular tachycardia, none had
      any arrhythmia recurrence for a median of 6.0 (3.3-93.5) months after a
      cavotricuspid isthmus or slow pathway ablation, respectively. There were no
      procedural complications. During the median follow-up of 19.0 (9.5-37.3) months
      after the last procedure, no patients experienced any inappropriate shocks.
      CONCLUSION: Catheter ablation is a feasible therapeutic option for treating ATa
      responsible for inappropriate shock(s) in patients with ICD.

PMID- 25061231
TI  - Healthy behaviours and mental health: findings from the German Health Update
      (GEDA).
AB  - BACKGROUND: Health risk behaviours such as smoking, physical inactivity and poor
      diet are independently associated with depression. However, there is a paucity of
      data examining associations between combined healthy behaviours and mental
      distress and depression. METHODS: Using cross-sectional data from a nationwide
      population-based sample of adults in Germany [German Health Update (GEDA) 2009
      and 2010 telephone surveys; n = 21 940 women, n = 17 061 men], we examined
      associations between five healthy behaviours and frequent mental distress (FMD)
      and self-reported diagnosed depression in the past 12 months. Healthy behaviours
      included non-smoking, low-risk alcohol drinking, regular sport, maintaining
      normal weight and healthy fruit and vegetable consumption. Multiple logistic
      regression analyses adjusted for potential confounders examined associations
      between the combined number of healthy behaviours and FMD and self-reported
      diagnosed depression. RESULTS: FMD was reported by 13.6 and 8.0% and diagnosed
      depression in the last 12 months by 8.3 and 4.7% of women and men, respectively.
      At least four of five assessed healthy behaviours were reported by 29.1% of women
      and 17.8% of men. Compared with those with less than two healthy behaviours,
      women and men with at least four behaviours were about half as likely to report
      FMD [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.44-0.64, and OR 0.52,
      95% CI 0.41-0.66, respectively) and women with at least four behaviours were less
      likely to report diagnosed depression (OR 0.76, 95% CI 0.61-0.95). CONCLUSION: A
      higher number of healthy behaviours are associated with a lower prevalence of FMD
      for both women and men and of self-reported diagnosed depression in women.

PMID- 25061232
TI  - Do lifestyle, health and social participation mediate educational inequalities in
      frailty worsening?
AB  - BACKGROUND: Lower educated older persons are at increased risk of becoming frail
      as compared with higher educated older persons. To reduce educational
      inequalities in the development of frailty, we investigated whether lifestyle,
      health and social participation mediate this relationship. METHODS: Longitudinal
      data of 14 082 European community-dwelling persons aged 55 years and older
      participating in the Survey on Health, Ageing, and Retirement in Europe (SHARE)
      in 2004 and 2006, were used. Associations of lifestyle (smoking behaviour and
      alcohol consumption), health (depression, memory function, chronic diseases) and
      social participation, with educational level and frailty worsening were
      investigated using regression models. In multinomial logistic regression
      analysis, mediators were added to models in which educational level was
      associated with worsening in frailty over 2 years follow-up. RESULTS: In all
      countries, frailty worsening was more prevalent among lower as compared with
      higher educated persons, although odds ratios were only statistically significant
      in five of the 11 countries included [ORs varying from 1.40 (95% CI: 1.06-1.84)
      to 1.61 (95% CI: 1.21-2.14)]. Except for smoking behaviour and memory function,
      the factors under study all showed associations with educational level and
      frailty worsening that met the conditions for mediation. After inclusion of the
      four relevant mediators, attenuation of odds ratios varied between 4.9 and 31.5%.
      CONCLUSION: While lifestyle, health and social participation were associated with
      frailty worsening over 2 years among European community-dwelling older persons,
      only small to moderate parts of educational inequalities in frailty worsening
      were explained by these factors.

PMID- 25061233
TI  - A stepped wedge cluster randomized control trial of dried blood spot testing to
      improve the uptake of hepatitis C antibody testing within UK prisons.
AB  - BACKGROUND: The prevalence of hepatitis C (HCV) is elevated within prison
      populations, yet diagnosis in prisons remains low. Dried blood spot testing
      (DBST) is a simple procedure for the detection of HCV antibodies; its impact on
      testing in the prison context is unknown. METHODS: We carried out a stepped-wedge
      cluster-randomized control trial of DBST for HCV among prisoners within five male
      prisons and one female prison. Each prison was a separate cluster. The order in
      which the intervention (training in use of DBST for HCV testing and logistic
      support) was introduced was randomized across clusters. The outcome measure was
      the HCV testing rate by prison. Imputation analysis was carried out to account
      for missing data. Planned and actual intervention times differed in some prisons;
      data were thus analysed by intention to treat (ITT) and by observed step times.
      RESULTS: There was insufficient evidence of an effect of the intervention on
      testing rate using either the ITT intervention time (OR: 0.84; 95% CI: 0.68-1.03;
      P = 0.088) or using the actual intervention time (OR: 0.86; 95% CI: 0.71-1.06; P
      = 0.153). This was confirmed by the pooled results of five imputed data sets.
      CONCLUSIONS: DBST as a stand-alone intervention was insufficient to increase HCV
      diagnosis within the UK prison setting. Factors such as staff training and
      allocation of staff time for regular clinics are key to improving service
      delivery. We demonstrate that prisons can conduct rigorous studies of new
      interventions, but data collection can be problematic. TRIAL REGISTRATION:
      International Standard Randomized Controlled Trial Number Register (ISRCTN number
      ISRCTN05628482).

PMID- 25061234
TI  - Early determinants of postsecondary education participation and degree
      attainment: Findings from an inner-city minority cohort.
AB  - Early determinants of college attendance and degree attainment for economically
      disadvantaged minority youth were examined in the present study. The study sample
      (n=1,379) was drawn from the Chicago Longitudinal Study (CLS), an on-going
      investigation of a panel of low-income minority children born at 1980, growing up
      in high-poverty neighborhoods in Chicago. Regression findings indicated that
      three factors in elementary grades can potentially improve both college
      attendance and BA degree completion for economically disadvantaged minority
      students: better classroom adjustment, high parent expectation in child's
      education, and better academic performance. Findings have implications for
      schools, educators, and policy makers.

PMID- 25061235
TI  - Guidelines in the Register of the Association of Scientific Medical Societies in
      Germany - A Quality Improvement Campaign.
AB  - The Association of Scientific Medical Societies in Germany (AWMF) is the umbrella
      organization of medical scientific societies in Germany. The development of
      guidelines goes back to an initiative of the medical scientific societies and is
      coordinated by the AWMF. Rules for the inclusion of guidelines in the AWMF
      Guideline Register have been defined including how guidelines are classified. S1
      guidelines are based only on recommendations by experts, whereas S2 guidelines
      require a structured consensus process or a systematic literature review. S3
      guidelines include both elements. In addition to compulsory disclosure of any
      potential conflict of interest, transparent handling of potential conflicts of
      interest is an important confidence-building measure. For years, the trend has
      been to develop higher order (S2/S3) guidelines, and the German Society for
      Gynecology and Obstetrics (DGGG) has been no exception to the trend. In addition
      to its responsibility for specific S2 and S3 guidelines, the DGGG is also
      involved in numerous other interdisciplinary guidelines. When developing a
      guideline, it is essential to define the guideline's scope, identify aspects
      which require improvement and agree on the goals. Target groups affected by the
      guidelines should be involved if they are interested. Different formats (long and
      short versions, practical instructions, conventional or electronic decision aids,
      patient versions) are useful to disseminate the guideline. The guideline can be
      adapted to local circumstances to encourage implementation of its
      recommendations. Implementation can be measured using quality indicators.
      Feedback from practitioners is important as this highlights areas which require
      improvement. The medical scientific societies in Germany can look back on almost
      two decades of work spent on developing guidelines, most of it done by unpaid
      voluntary contributors, making this a very successful quality initiative.

PMID- 25061236
TI  - Synthesis of phospholipids on a glyceric acid scaffold: design and preparation of
      phospholipase A2 specific substrates.
AB  - Synthesis of a new series of phospholipid analogues to serve as activity-based
      probes of secretory phospholipase A2 enzymes is reported. The synthesis is based
      upon 1) preparation of long-chain esters and amides of glyceric acid, followed by
      2) regioselective derivatization of the diol function of the molecule to achieve
      phosphorylation at the primary hydroxyl group, and to introduce the incipient sn
      2-ester group of the target compounds. The sequence has been shown to allow
      incorporation of fluorescent, paramagnetic, and redox-active reporter groups,
      leading to phospholipid analogues applicable to detect and measure enzyme
      activity, to develop highly specific, real-time spectroscopic assay of
      phospholipase A2 enzymes, as well as to track the metabolic fate of the
      hydrolysis products. The synthetic method has a great deal of flexibility to open
      the way to the design and synthesis of activity-probes for other phospholipid
      metabolizing enzymes as well.

PMID- 25061237
TI  - Thermally-Induced Substrate Release Via Intramolecular Cyclizations of Amino
      Esters and Amino Carbonates.
AB  - The relative cleavage of an alcohol from a panel of amino esters and amino
      carbonates via intramolecular cyclization was examined as a mechanism for
      substrate release. Thermal stability at 37  degrees C was observed only for the 7
      membered ring progenitors. Applicability of the approach was illustrated by delta
      lactam formation within a poly(dimethylsiloxane) microchannel for release of a
      captured fluorescent probe.

PMID- 25061238
TI  - A mild and efficient AgSbF6-catalyzed synthesis of fully substituted pyrroles
      through a sequential propargylation/amination/cycloisomerization reaction.
AB  - Development of an efficient synthesis of fully substituted pyrroles via a
      sequential as a catalyst. The propargylation/amination/cycloisomerization was
      accomplished using AgSbF6 one-pot three-component reaction of propargylic
      alcohols, 1,3-dicarbonyl compounds, and primary amines proceeds at a mild
      temperature, which prevents the formation of furan by-product. The reaction was
      also successfully applied to the more basic aliphatic amines with the addition of
      1.1 eq. of acetic acid.

PMID- 25061239
TI  - Relaxor-based ferroelectric single crystals: growth, domain engineering,
      characterization and applications.
AB  - In the past decade, domain engineered relaxor-PT ferroelectric single crystals,
      including (1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT), (1-x)Pb(Zn1/3Nb2/3)O3-xPbTiO3
      (PZN-PT) and (1-x-y)Pb(In1/2Nb1/2)O3-yPb(Mg1/3Nb2/3)O3-xPbTiO3 (PIN-PMN-PT), with
      compositions near the morphotropic phase boundary (MPB) have triggered a
      revolution in electromechanical devices owing to their giant piezoelectric
      properties and ultra-high electromechanical coupling factors. Compared to
      traditional PbZr1-x Ti x O3 (PZT) ceramics, the piezoelectric coefficient d33 is
      increased by a factor of 5 and the electromechanical coupling factor k33 is
      increased from < 70% to > 90%. Many emerging rich physical phenomena, such as
      charged domain walls, multi-phase coexistence, domain pattern symmetries, etc.,
      have posed challenging fundamental questions for scientists. The superior
      electromechanical properties of these domain engineered single crystals have
      prompted the design of a new generation electromechanical devices, including
      sensors, transducers, actuators and other electromechanical devices, with greatly
      improved performance. It took less than 7 years from the discovery of larger size
      PMN-PT single crystals to the commercial production of the high-end ultrasonic
      imaging probe "PureWave". The speed of development is unprecedented, and the
      research collaboration between academia and industrial engineers on this topic is
      truly intriguing. It is also exciting to see that these relaxor-PT single
      crystals are being used to replace traditional PZT piezoceramics in many new
      fields outside of medical imaging. The new ternary PIN-PMN-PT single crystals,
      particularly the ones with Mn-doping, have laid a solid foundation for
      innovations in high power acoustic projectors and ultrasonic motors, hinting
      another revolution in underwater SONARs and miniature actuation devices. This
      article intends to provide a comprehensive review on the development of relaxor
      PT single crystals, spanning material discovery, crystal growth techniques,
      domain engineering concept, and full-matrix property characterization all the way
      to device innovations. It outlines a truly encouraging story in materials science
      in the modern era. All key references are provided and 30 complete sets of
      material parameters for different types of relaxor-PT single crystals are listed
      in the Appendix. It is the intension of this review article to serve as a
      resource for those who are interested in basic research and practical
      applications of these relaxor-PT single crystals. In addition, possible
      mechanisms of giant piezoelectric properties in these domain-engineered relaxor
      PT systems will be discussed based on contributions from polarization rotation
      and charged domain walls.

PMID- 25061240
TI  - Changing crops in response to climate: virtual Nang Rong, Thailand in an agent
      based simulation.
AB  - The effects of extended climatic variability on agricultural land use were
      explored for the type of system found in villages of northeastern Thailand. An
      agent based model developed for the Nang Rong district was used to simulate land
      allotted to jasmine rice, heavy rice, cassava, and sugar cane. The land use
      choices in the model depended on likely economic outcomes, but included elements
      of bounded rationality in dependence on household demography. The socioeconomic
      dynamics are endogenous in the system, and climate changes were added as
      exogenous drivers. Villages changed their agricultural effort in many different
      ways. Most villages reduced the amount of land under cultivation, primarily with
      reduction in jasmine rice, but others did not. The variation in responses to
      climate change indicates potential sensitivity to initial conditions and path
      dependence for this type of system. The differences between our virtual villages
      and the real villages of the region indicate effects of bounded rationality and
      limits on model applications.

PMID- 25061241
TI  - The ups and downs of synapses during sleep and learning.

PMID- 25061242
TI  - Work-life balance.

PMID- 25061243
TI  - Sleep apnea: a redox edge with aging?

PMID- 25061244
TI  - Sleep promotes cortical response potentiation following visual experience.
AB  - STUDY OBJECTIVES: Sleep has been hypothesized to globally reduce synaptic
      strength. However, recent findings suggest that in the context of learning and
      memory consolidation, sleep may promote synaptic potentiation. We tested the
      requirement for sleep in a naturally occurring form of experience-dependent
      synaptic potentiation in the adult mouse visual cortex (V1), which is initiated
      by patterned visual experience. DESIGN: Visual responses were recorded in
      individual V1 neurons before and after presentation of an oriented grating
      stimulus, and after subsequent sleep or sleep deprivation. MEASUREMENTS AND
      RESULTS: We find that V1 response potentiation-associated with a shift in
      orientation preference in favor of the presented stimulus-occurs only after sleep
      and only during the entrained circadian sleep phase, and is blocked by sleep
      deprivation. Induction of plasticity following stimulus presentation is
      associated with an increase in principal neuron firing in V1, which is present in
      all behavioral states and occurs regardless of time of day. Sleep dependent
      potentiation is proportional to phase-locking of neuronal activity with
      thalamocortical spindle oscillations. CONCLUSIONS: Our results suggest that sleep
      can promote cortical synaptic potentiation in vivo, and that this potentiation
      may be mediated by slow wave sleep spindles. CITATION: Aton SJ, Suresh A,
      Broussard C, Frank MG. Sleep promotes cortical response potentiation following
      visual experience.

PMID- 25061245
TI  - Sleep duration and age-related changes in brain structure and cognitive
      performance.
AB  - STUDY OBJECTIVES: To investigate the contribution of sleep duration and quality
      to age-related changes in brain structure and cognitive performance in relatively
      healthy older adults. DESIGN: Community-based longitudinal brain and cognitive
      aging study using a convenience sample. SETTING: Participants were studied in a
      research laboratory. PARTICIPANTS: Relatively healthy adults aged 55 y and older
      at study commencement. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants
      underwent magnetic resonance imaging and neuropsychological assessment every 2 y.
      Subjective assessments of sleep duration and quality and blood samples were
      obtained. Each hour of reduced sleep duration at baseline augmented the annual
      expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate
      in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after
      controlling for the effects of age, sex, education, and body mass index. In
      contrast, global sleep quality at baseline did not modulate either brain or
      cognitive aging. High-sensitivity C-reactive protein, a marker of systemic
      inflammation, showed no correlation with baseline sleep duration, brain
      structure, or cognitive performance. CONCLUSIONS: In healthy older adults, short
      sleep duration is associated with greater age-related brain atrophy and cognitive
      decline. These associations are not associated with elevated inflammatory
      responses among short sleepers. CITATION: Lo JC, Loh KK, Zheng H, Sim SK, Chee
      MW. Sleep duration and age-related changes in brain structure and cognitive
      performance.

PMID- 25061246
TI  - Subjective and objective sleep disturbance and longitudinal risk of depression in
      a cohort of older women.
AB  - OBJECTIVE: To investigate the longitudinal relationship between subjective and
      objective sleep disturbance and depressive symptoms. DESIGN: Longitudinal.
      SETTING: Three US clinical centers. PARTICIPANTS: Nine hundred fifty-two
      community-dwelling older women (70 y or older). MEASUREMENTS: At baseline,
      subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index
      (PSQI) and objective sleep measures were assessed with wrist actigraphy.
      Depressive symptoms were assessed with the Geriatric Depression Scale (GDS) at
      baseline and approximately 5 y later. The analysis was restricted to women with
      few (GDS 0-2) depressive symptoms at baseline. RESULTS: There was an independent
      association between greater PSQI score (per standard deviation increase,
      indicating worse subjective sleep quality) at baseline and greater odds of
      worsening depressive symptoms (>= 2-point increase in GDS) (Multivariate Odds
      Ratio [MOR] 1.19, confidence interval [CI] 1.01-1.40, P = 0.036). Higher scores
      specifically on the sleep quality (MOR 1.41, CI 1.13-1.77, P < 0.003) and sleep
      latency (MOR 1.21, CI 1.03-1.41, P = 0.018) PSQI subscales were also associated
      with greater odds for worsening depressive symptoms. Objective assessments
      revealed an association between baseline prolonged wake after sleep onset (WASO
      >= 60 min) and worsening depressive symptoms at follow-up (MOR 1.36, CI 1.01
      1.84, P = 0.046). There were no associations between other objectively assessed
      sleep measures and worsening depressive symptoms. CONCLUSIONS: In older women
      with few or no depressive symptoms at baseline, those with more subjectively
      reported sleep disturbance and more objectively assessed fragmentation of sleep
      at baseline had greater odds of worsening depressive symptoms 5 y later. Future
      studies investigating this relationship in more detail are indicated. CITATION:
      Maglione JE, Ancoli-Israel S, Peters KW, Paudel ML, Yaffe K, Ensrud KE, Stone KL,
      Study of Osteoporotic Fractures Research Group. Subjective and objective sleep
      disturbance and longitudinal risk of depression in a cohort of older women.

PMID- 25061247
TI  - Hippocampal substructural vulnerability to sleep disturbance and cognitive
      impairment in patients with chronic primary insomnia: magnetic resonance imaging
      morphometry.
AB  - STUDY OBJECTIVES: Despite compelling evidence from animal studies indicating
      hippocampal subfield-specific vulnerability to poor sleep quality and related
      cognitive impairment, there have been no human magnetic resonance imaging (MRI)
      studies investigating the relationship between hippocampal subfield volume and
      sleep disturbance. Our aim was to investigate the pattern of volume changes
      across hippocampal subfields in patients with primary insomnia relative to
      controls. DESIGN: Pointwise morphometry allowed for volume measurements of
      hippocampal regions on T1-weighted MRI. SETTING: University hospital. PATIENTS:
      Twenty-seven unmedicated patients (age: 51.2 +/- 9.6 y) and 30 good sleepers as
      controls (50.4 +/- 7.1 y). INTERVENTIONS: N/A. MEASUREMENTS: We compared
      hippocampal subfield volumes between patients and controls and correlated volume
      with clinical and neuropsychological features in patients. RESULTS: Patients
      exhibited bilateral atrophy across all hippocampal subfields (P < 0.05
      corrected). Cornu ammonis (CA) 1 subfield atrophy was associated with worse sleep
      quality (higher Pittsburgh Sleep Quality Index and higher arousal index of
      polysomnography) (r < -0.45, P < 0.005). The volume of the combined region,
      including the dentate gyrus (DG) and CA3-4, negatively correlated with verbal
      memory, verbal information processing, and verbal fluency in patients (|r| >
      0.45, P < 0.05). Hemispheric volume asymmetry of this region (left smaller than
      right) was associated with impaired verbal domain functions (r = 0.50, P <
      0.005). CONCLUSION: Hippocampal subfield atrophy in chronic insomnia suggests
      reduced neurogenesis in the dentate gyrus (DG) and neuronal loss in the cornu
      ammonis (CA) subfields in conditions of sleep fragmentation and related chronic
      stress condition. Atrophy in the CA3-4-DG region was associated with impaired
      cognitive functions in patients. These observations may provide insight into
      pathophysiological mechanisms that make patients with chronic sleep disturbance
      vulnerable to cognitive impairment. CITATION: Joo EY, Kim H, Suh S, Hong SB.
      Hippocampal substructural vulnerability to sleep disturbance and cognitive
      impairment in patients with chronic primary insomnia: magnetic resonance imaging
      morphometry.

PMID- 25061248
TI  - Moderators and mediators of the relationship between stress and insomnia:
      stressor chronicity, cognitive intrusion, and coping.
AB  - STUDY OBJECTIVES: To assess moderators, such as stressor chronicity, and
      mediators, including stress response in the form of cognitive intrusion and
      coping behavior, of the prospective association between naturalistic stress and
      incident insomnia. DESIGN: Longitudinal. SETTING: Epidemiological. PARTICIPANTS:
      A community-based sample of good sleepers (n = 2,892) with no lifetime history of
      insomnia. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Participants reported
      the number of stressful events they had encountered at baseline, as well as the
      perceived severity and chronicity of each event. Similarly, volitional stress
      responses such as coping, as well as more involuntary responses such as cognitive
      intrusion were assayed for each stressor. Follow-up assessment 1 y hence revealed
      an insomnia incidence rate of 9.1%. Stress exposure was a significant predictor
      of insomnia onset, such that the odds of developing insomnia increased by 19% for
      every additional stressor. Chronicity significantly moderated this relationship,
      such that the likelihood of developing insomnia as a result of stress exposure
      increased as a function of chronicity. Cognitive intrusion significantly mediated
      the association between stress exposure and insomnia. Finally, three specific
      coping behaviors also acted as mediators: behavioral disengagement, distraction,
      and substance use. CONCLUSIONS: Most studies characterize the relationship
      between stress exposure and insomnia as a simple dose-response phenomenon.
      However, our data suggest that certain stressor characteristics significantly
      moderate this association. Stress response in the form of cognitive intrusion and
      specific maladaptive coping behaviors mediate the effects of stress exposure.
      These findings highlight the need for a multidimensional approach to stress
      assessment in future research and clinical practice. CITATION: Pillai V, Roth T,
      Mullins HM, Drake CL. Moderators and mediators of the relationship between stress
      and insomnia: stressor chronicity, cognitive intrusion, and coping.

PMID- 25061249
TI  - Long-term effectiveness and compliance of positional therapy with the sleep
      position trainer in the treatment of positional obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVES: To investigate effectiveness, long-term compliance, and effects
      on subjective sleep of the Sleep Position Trainer (SPT) in patients with position
      dependent obstructive sleep apnea syndrome (POSAS). DESIGN: Prospective,
      multicenter cohort study. PATIENTS OR PARTICIPANTS: Adult patients with mild and
      moderate POSAS were included. INTERVENTIONS: Patients were [corrected] asked to
      use the SPT for 6 mo. At baseline and after 1, 3, and 6 mo, questionnaires would
      be completed: Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index
      (PSQI), Functional Outcomes of Sleep Questionnaire (FOSQ), and questions related
      to SPT use. MEASUREMENTS AND RESULTS: One hundred forty-five patients were
      included. SPT use and SPT data could not be retrieved in 39 patients. In the
      remaining 106 patients, median percentage of supine sleep decreased rapidly
      during SPT's training phase (day 3 to 9) to near-total avoidance of supine sleep.
      This decrease was maintained during the following months of treatment (21% at
      baseline versus 3% at 6 mo). SPT compliance, defined as more than 4 h of nightly
      use, was 64.4%. Regular use, defined as more than 4 h of usage over 5 nights/w,
      was 71.2%. Subjective compliance and regular use were 59.8% and 74.4%,
      respectively. Median ESS (11 to 8), PSQI (8 to 6), and FOSQ (87 to 103) values
      significantly improved compared with baseline. CONCLUSIONS: Positional therapy
      using the Sleep Position Trainer (SPT) effectively diminished the percentage of
      supine sleep and subjective sleepiness and improved sleep related quality of life
      in patients with mild to moderate position-dependent obstructive sleep apnea
      syndrome. SPT treatment appeared to have sustained effects over 6 months. SPT
      compliance and regular use rate were relatively good. Subjective and objective
      compliance data corresponded well. The lack of a placebo-controlled group limited
      the efficacy of conclusions. CITATION: van Maamen JP, de Vries N. Long-term
      effectiveness and compliance of positional therapy with the Sleep Position
      Trainer in the treatment of positional obstructive sleep apnea syndrome.

PMID- 25061250
TI  - Work time control and sleep disturbances: prospective cohort study of Finnish
      public sector employees.
AB  - OBJECTIVES: Employee control over work times has been associated with favorable
      psychosocial and health-related outcomes, but the evidence regarding sleep
      quality remains inconclusive. We examined cross-sectional and prospective
      associations between work time control and sleep disturbances in a large working
      population, taking into account total hours worked. METHODS: The data were from a
      full-panel longitudinal cohort study of Finnish public sector employees who
      responded to questions on work time control and sleep disturbances in years 2000
      2001, 2004-2005, 2008-2009, and 2012. The analysis of cross-sectional
      associations was based on 129,286 person measurements from 68,089 participants
      (77% women) aged 17-73 years (mean 43.1). Data from 16,503 participants were used
      in the longitudinal analysis. Log-binomial regression analysis with the
      generalized estimating equations method was used. RESULTS: Consistently in both
      cross-sectional and longitudinal models, less control over work time was
      associated with greater sleep disturbances in the total population and among
      those working normal 40-hour weeks. Among participants working more than 40 hours
      a week, work time that was both very high (cross-sectional prevalence ratio
      compared to intermediate work time control [PR] 1.32, 95% confidence interval
      [CI] 1.05-1.65) and very low (PR 1.23, 95% CI 1.08-1.39) was associated with
      sleep disturbances, after adjustment for potential confounding factors.
      CONCLUSIONS: These data suggest that having few opportunities to influence the
      duration and positioning of work time may increase the risk of sleep disturbances
      among employees. For persons working long hours, very high levels of control over
      working times were also associated with increased risk of sleep disturbances.
      CITATION: Salo P, Ala-Mursula L, Rod NH, Tucker P, Pentti J, Kivimaki M, Vahtera
      J. Work time control and sleep disturbances: prospective cohort study of Finnish
      public sector employees.

PMID- 25061251
TI  - Obstructive sleep apnea in older adults is a distinctly different physiological
      phenotype.
AB  - STUDY OBJECTIVES: Current evidence suggests that the pathological mechanisms
      underlying obstructive sleep apnea (OSA) are altered with age. However, previous
      studies examining individual physiological traits known to contribute to OSA
      pathogenesis have been assessed in isolation, primarily in healthy individuals.
      DESIGN: We assessed the four physiological traits responsible for OSA in a group
      of young and old patients with OSA. SETTING: Sleep research laboratory.
      PARTICIPANTS: Ten young (20-40 y) and old (60 y and older) patients with OSA
      matched by body mass index and sex. MEASUREMENTS AND RESULTS: Pharyngeal
      anatomy/collapsibility, loop gain (LG), upper airway muscle responsiveness/gain
      (UAG) and the respiratory arousal threshold were determined using multiple 2- to
      3-min decreases or drops in continuous positive airway pressure (CPAP). Passive
      pharyngeal anatomy/collapsibility was quantified as the ventilation at CPAP = 0
      cmH2O immediately after the CPAP drop. LG was defined as the ratio of the
      ventilatory overshoot to the preceding reduction in ventilation. UAG was taken as
      the ratio of the increase in ventilation to the increase in ventilatory drive
      across the pressure drop. Arousal threshold was estimated as the ventilatory
      drive that caused arousal. Veupnea was quantified as the mean ventilation prior
      to the pressure drop. In comparison with younger patients with OSA, older
      patients had a more collapsible airway (ventilation at 0 cmH2O = 3.4 +/- 0.9
      versus 1.5 +/- 0.7 L/min; P = 0.05) but lower Veupnea (8.2 +/- 0.5 versus 6.1 +/-
      0.4 L/min; P < 0.01) and a lower LG (5.0 +/- 0.7 versus 2.9 +/- 0.5; P < 0.05).
      The remaining traits were similar between groups. CONCLUSIONS: Our data suggest
      that airway anatomy/collapsibility plays a relatively greater pathogenic role in
      older adults, whereas a sensitive ventilatory control system is a more prominent
      trait in younger adults with obstructive sleep apnea. CITATION: Edwards BA,
      Wellman A, Sands SA, Owens RL, Eckert DJ, White DP, Malhotra A. Obstructive sleep
      apnea in older adults is a distinctly different physiological phenotype.

PMID- 25061252
TI  - Examining the mechanism of action of a new device using oral pressure therapy for
      the treatment of obstructive sleep apnea.
AB  - STUDY OBJECTIVES: The objective of this study was to explore the mechanism of
      action of the oral pressure therapy (OPT) device, a new treatment for sleep
      apnea. DESIGN: Case series. SETTING: Academic medical center. PATIENTS: Fifteen
      subjects with sleep apnea who had been successfully treated (responders) with the
      OPT device and 4 subjects who were not successfully treated (non-responders) with
      the OPT device. INTERVENTIONS: All subjects underwent a MRI (without the device,
      with the device in place without vacuum and with the device in place with vacuum)
      to examine the biomechanical changes associated with the OPT device. MEASUREMENTS
      AND RESULTS: Oral pressure therapy significantly (P = 0.002) increased the size
      of the retropalatal airway in both the lateral and anterior-posterior dimensions
      by moving the soft palate anteriorly and superiorly and the anterior-superior
      segment of the tongue forward, toward the teeth. The percentage and absolute
      increase in the cross-sectional area of the retropalatal region, the superior
      movement of the soft palate, and the anterior displacement of the tongue were
      significantly greater in the responders than in the non-responders. In
      responders, there were significant increases in the mean (P = 0.002), maximum (P
      = 0.0002), and minimum (P = 0.04) cross-sectional areas of the retropalatal
      region with the OPT device. However, in the retroglossal region, airway caliber
      decreased with the OPT device. CONCLUSIONS: In those who responded to oral
      pressure therapy, it increased airway caliber in the retropalatal region by
      moving the soft palate anteriorly and superiorly and the anterior-superior
      segment of the tongue forward. CITATION: Schwab RJ, Kim C, Siegel L, Keenan BT,
      Black J, Farid-Moayer M, Podmore J, Vaska M. Examining the mechanism of action of
      a new device using oral pressure therapy for the treatment of obstructive sleep
      apnea.

PMID- 25061254
TI  - Sparse Additive Ordinary Differential Equations for Dynamic Gene Regulatory
      Network Modeling.
AB  - The gene regulation network (GRN) is a high-dimensional complex system, which can
      be represented by various mathematical or statistical models. The ordinary
      differential equation (ODE) model is one of the popular dynamic GRN models. High
      dimensional linear ODE models have been proposed to identify GRNs, but with a
      limitation of the linear regulation effect assumption. In this article, we
      propose a sparse additive ODE (SA-ODE) model, coupled with ODE estimation methods
      and adaptive group LASSO techniques, to model dynamic GRNs that could flexibly
      deal with nonlinear regulation effects. The asymptotic properties of the proposed
      method are established and simulation studies are performed to validate the
      proposed approach. An application example for identifying the nonlinear dynamic
      GRN of T-cell activation is used to illustrate the usefulness of the proposed
      method.

PMID- 25061253
TI  - Brain tissue hypoxia and oxidative stress induced by obstructive apneas is
      different in young and aged rats.
AB  - STUDY OBJECTIVES: To test the hypotheses that brain oxygen partial pressure
      (PtO2) in response to obstructive apneas changes with age and that it might lead
      to different levels of cerebral tissue oxidative stress. DESIGN: Prospective
      controlled animal study. SETTING: University laboratory. PARTICIPANTS: Sixty-four
      male Wistar rats: 32 young (3 mo old) and 32 aged (18 mo). INTERVENTIONS:
      Protocol 1: Twenty-four animals were subjected to obstructive apneas (50
      apneas/h, lasting 15 sec each) or to sham procedure for 50 min. Protocol 2: Forty
      rats were subjected to obstructive apneas or sham procedure for 4 h. MEASUREMENTS
      AND RESULTS: Protocol 1: Real-time PtO2 measurements were performed using a fast
      response oxygen microelectrode. During successive apneas cerebral cortex PtO2
      presented a different pattern in the two age groups; there was a fast increase in
      young rats, whereas it remained without significant changes between the beginning
      and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress
      assessed by lipid peroxidation increased after apneas in young rats (1.34 +/-
      0.17 nmol/mg of protein) compared to old ones (0.63 +/- 0.03 nmol/mg), where a
      higher expression of antioxidant enzymes was observed. CONCLUSIONS: The results
      suggest that brain oxidative stress in aged rats is lower than in young rats in
      response to recurrent apneas, mimicking obstructive sleep apnea. This could be
      due to the different PtO2 response observed between age groups and the increased
      antioxidant expression in aged rats. CITATION: Dalmases M, Torres M, Marquez
      Kisinousky L, Almendros I, Planas AM, Embid C, Martinez-Garcia MA, Navajas D,
      Farre R, Montserrat JM. Brain tissue hypoxia and oxidative stress induced by
      obstructive apneas is different in young and aged rats.

PMID- 25061255
TI  - Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints.
AB  - Evaluation of candidate surrogate endpoints using individual patient data from
      multiple clinical trials is considered the gold standard approach to validate
      surrogates at both patient and trial levels. However, this approach assumes the
      availability of patient-level data from a relatively large collection of similar
      trials, which may not be possible to achieve for a given disease application. One
      common solution to the problem of too few similar trials involves performing
      trial-level surrogacy analyses on trial sub-units (e.g., centers within trials),
      thereby artificially increasing the trial-level sample size for feasibility of
      the multi-trial analysis. To date, the practical impact of treating trial sub
      units (centers) identically to trials in multi-trial surrogacy analyses remains
      unexplored, and conditions under which this ad hoc solution may in fact be
      reasonable have not been identified. We perform a simulation study to identify
      such conditions, and demonstrate practical implications using a multi-trial
      dataset of patients with early stage colon cancer.

PMID- 25061256
TI  - Inadequate child supervision: The role of alcohol outlet density, parent drinking
      behaviors, and social support.
AB  - Supervisory neglect, or the failure of a caregiver to appropriately supervise a
      child, is one of the predominant types of neglectful behaviors, with alcohol use
      being considered a key antecedent to inadequate supervision of children. The
      current study builds on previous work by examining the role of parental drinking
      and alcohol outlet densities while controlling for caregiver and child
      characteristics. Data were obtained from 3,023 participants via a telephone
      survey from 50 cities throughout California. The telephone survey included items
      on neglectful parenting practices, drinking behaviors, and socio-demographic
      characteristics. Densities of alcohol outlets were measured for each of the 202
      zip codes in the study. Multilevel Bernoulli models were used to analyze the
      relationship between four supervisory neglect parenting practices and individual
      level and zip code-level variables. In our study, heavy drinking was only
      significantly related to one of our four outcome variables (leaving a child where
      he or she may not be safe). The density of on premise alcohol outlets was
      positively related to leaving a child home alone when an adult should be present.
      This study demonstrates that discrete relationships exist between alcohol related
      variables, social support, and specific supervisory neglect subtypes at the
      ecological and individual levels.

PMID- 25061257
TI  - Child Perceived Parenting Behavior: Childhood Anxiety and Related Symptoms.
AB  - The current study examined the relationship between child-reported parenting
      behaviors and children's anxiety, depressive, and externalizing symptoms. Youth
      ages 7 - 14 (N = 175; 52.6% male) and their parents seeking treatment for child
      anxiety were evaluated. The parenting behaviors that were measured separately
      included father's and mother's acceptance, psychological control, and
      firm/behavioral control. Children's symptoms were assessed using diagnostic
      interviews, self-reports, parent-reports, and teacher-reports. Independent t
      tests revealed that children diagnosed with a primary anxiety disorder perceived
      higher parental control than children without an anxiety disorder. Results from
      regression analyses indicated that child-reported maternal acceptance was
      associated with lower symptoms of child anxiety, depression, and externalizing
      behavior, whereas psychological control predicted higher symptoms. Further, child
      reported depressive symptoms moderated the relationship between maternal
      psychological control and children's anxiety, such that the relationship was
      weaker for anxious children with more depressive symptoms. The current findings
      support that children's perception of parenting behavior is associated with
      anxiety, and children's depressive symptoms moderate this relationship.

PMID- 25061258
TI  - Just-About-Right and ideal scaling provide similar insights into the influence of
      sensory attributes on liking.
AB  - Just-about-right (JAR) scaling is criticized for measuring attribute intensity
      and acceptability simultaneously. Using JAR scaling, an attribute is evaluated
      for its appropriateness relative to one's hypothetical ideal level that is pre
      defined at the middle of a continuum. Alternatively, ideal scaling measures these
      two constructs separately. Ideal scaling allows participants to rate their ideal
      freely on the scale (i.e., without assuming the "Too Little" and "Too Much"
      regions are equal in size). We hypothesized that constraining participants' ideal
      to the center point, as is done in the JAR scale, may cause a scaling bias and,
      thereby, influence the magnitude of "Too Little" and "Too Much". Furthermore, we
      hypothesized that the magnitude of "Too Little" and "Too Much" would influence
      liking to different extents. Coffee-flavored dairy beverages (n=20) were
      formulated using a fractional, constrained-mixture design that varied the ratio
      of water, milk, coffee extract, and sucrose. Participants tasted 4 of 20
      prototypes that were served in a monadic sequential order using a balanced
      incomplete block design. Data reported here are for participants randomly
      assigned to one of two research conditions: ideal scaling (n=129) or JAR scaling
      (n=132). For both conditions, participants rated overall liking using a 9-point
      hedonic scale. Four attributes (sweetness, milk flavor, coffee flavor and
      thickness) were evaluated. The reliability of an individual participant's ideal
      rating for an attribute was evaluated using the standard deviation of their ideal
      ratings (n=4). All data from a participant were eliminated from further analyses
      when his/her standard deviation of the ideal ratings for any of the four rated
      attributes was identified as a statistical outlier. This resulted in the
      elimination of 15 of 129 (12 %) of participants in the ideal scaling group.
      Multiple linear regression was employed to model liking as a function of "Too
      Little" or "Too Much" attribute intensities. Mean ideal ratings (averaged across
      participants) for all four attributes were significantly different from the
      central point of the scale (i.e., 50). However, Coffee flavor was the only
      attribute for which the mean ideal rating (57.2) fell outside the central 10%
      (45.0-55.0). Even so, the magnitude of "Too Little" and "Too Much" was not
      affected by the scaling method. The influence of the magnitude of "Too Little"
      and "Too Much" on liking was asymmetrical. Both scaling methods agreed that
      sweetness and coffee flavor were the main sensory attributes affecting liking.
      Overall, JAR scaling and ideal scaling were comparable for measuring "Too Little"
      and "Too Much", and identifying the main factors affecting liking.

PMID- 25061259
TI  - Biological treatments in Behcet's disease: beyond anti-TNF therapy.
AB  - Behcet's disease (BD) is universally recognized as a multisystemic inflammatory
      disease of unknown etiology with chronic course and unpredictable exacerbations:
      its clinical spectrum varies from pure vasculitic manifestations with thrombotic
      complications to protean inflammatory involvement of multiple organs and tissues.
      Treatment has been revolutionized by the progressed knowledge in the pathogenetic
      mechanisms of BD, involving dysfunction and oversecretion of multiple
      proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) alpha,
      interleukin- (IL-) 1beta, and IL-6. However, although biological treatment with
      anti-TNF-alpha agents has been largely demonstrated to be effective in BD, not
      all patients are definite responders, and this beneficial response might drop off
      over time. Therefore, additional therapies for a subset of refractory patients
      with BD are inevitably needed. Different agents targeting various cytokines and
      their receptors or cell surface molecules have been studied: the IL-1 receptor
      has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6
      receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B
      lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all
      current experiences and the most recent evidence regarding these novel approaches
      with biological drugs other than TNF-alpha blockers in BD, providing a valuable
      addition to the actually available therapeutic armamentarium.

PMID- 25061261
TI  - Biomarkers in rheumatoid arthritis.

PMID- 25061260
TI  - An overview of the role of innate lymphoid cells in gut infections and
      inflammation.
AB  - Innate lymphoid cells (ILCs) are a group of hematopoietic cells devoid of antigen
      receptors that have important functions in lymphoid organogenesis, in the defense
      against extracellular pathogens, and in the maintenance of the epithelial
      barrier. Three distinct groups of ILCs have been identified on the basis of
      phenotypic and functional criteria and termed ILCs1, ILCs2, and ILCs3.
      Specifically, ILCs1 express the transcription factor T-bet and secrete T helper
      type-1- (Th1-) related cytokines, ILCs2 are dependent on the transcription factor
      RORalpha and express Gata-3 and the chemokine receptor homologous molecule
      (CRTH2) and produce Th2-related cytokines, and ILCs3 express the transcription
      factor RORgammat and synthesize interleukin- (IL-) 17, IL-22, and, under specific
      stimuli, interferon-gamma. ILCs represent a relatively small population in the
      gut, but accumulating evidence suggests that these cells could play a decisive
      role in orchestrating both protective and detrimental immune responses. In this
      review, we will summarize the present knowledge on the distribution of ILCs in
      the intestinal mucosa, with particular focus on their role in the control of both
      infections and effector cytokine response in immune-mediated pathologies. 

PMID- 25061262
TI  - 25-Hydroxyvitamin D, IL-31, and IL-33 in children with allergic disease of the
      airways.
AB  - Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33
      correlate with Th2-associated cytokines in allergic disease. We investigated
      whether low vitamin D is linked with circulating IL-31 and IL-33 in children with
      allergic disease of the airways. 25-Hydroxyvitamin D [25(OH) Vit D], IL-31, and
      IL-33 plasma levels were measured in 28 controls (HC), 11 allergic rhinitis (AR)
      patients, and 35 allergic asthma with rhinitis (AAR) patients. We found
      significant lower levels of 25(OH) Vit D in AR and in AAR than in HC. IL-31 and
      IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33
      positively correlated in AR and AAR. 25(OH) Vit D deficient AAR had higher levels
      of blood eosinophils, exacerbations, disease duration, and total IgE than
      patients with insufficient or sufficient 25(OH) Vit D. In AAR 25(OH) Vit D levels
      inversely correlated with total allergen sIgE score and total atopy index. IL-31
      and IL-33 did not correlate with 25(OH) Vit D in AR and AAR. In conclusion, low
      levels of 25(OH) Vit D might represent a risk factor for the development of
      concomitant asthma and rhinitis in children with allergic disease of the airways
      independently of IL-31/IL-33 Th2 activity. 

PMID- 25061263
TI  - Genetic vaccination against experimental infection with myotropic parasite
      strains of Trypanosoma cruzi.
AB  - In earlier studies, we reported that a heterologous prime-boost regimen using
      recombinant plasmid DNA followed by replication-defective adenovirus vector, both
      containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote
      surface protein (ASP) 2, provided protective immunity against experimental
      infection with a reticulotropic strain of this human protozoan parasite. Herein,
      we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged
      with myotropic parasite strains (Brazil and Colombian). Initially, we determined
      that the coadministration during priming of a DNA plasmid containing the murine
      IL-12 gene improved the immune response and was essential for protective immunity
      elicited by the heterologous prime-boost regimen in susceptible male mice against
      acute lethal infections with these parasites. The prophylactic or therapeutic
      vaccination of resistant female mice led to a drastic reduction in the number of
      inflammatory infiltrates in cardiac and skeletal muscles during the chronic phase
      of infection with either strain. Analysis of the electrocardiographic parameters
      showed that prophylactic vaccination reduced the frequencies of sinus arrhythmia
      and atrioventricular block. Our results confirmed that prophylactic vaccination
      using the TS and ASP-2 genes benefits the host against acute and chronic
      pathologies caused by T. cruzi and should be further evaluated for the
      development of a veterinary or human vaccine against Chagas disease. 

PMID- 25061265
TI  - Effective Clinical Supervision in Substance Use Disorder Treatment Programs and
      Counselor Job Performance.
AB  - When mental health counselors have limited and/or inadequate training in
      substance use disorders (SUDs), effective clinical supervision (ECS) may advance
      their professional development. The purpose of the current study was to
      investigate whether ECS is related to the job performance of SUD counselors. Data
      were obtained in person via paper-and-pencil surveys from 392 matched SUD
      counselor-clinical supervisor dyads working in 27 SUD treatment organizations
      across the United States. ECS was rated by counselors and measured with five
      multi-item scales (i.e., sponsoring counselors' careers, providing challenging
      assignments, role modeling, accepting/confirming counselors' competence, overall
      supervisor task proficiency). Clinical supervisors rated counselors' job
      performance, which was measured with two multi-item scales (i.e., task
      performance, performance within supervisory relationship). Using mixed-effects
      models, we found that most aspects of ECS are related to SUD counselor job
      performance. Thus, ECS may indeed enhance counselors' task performance and
      performance within the supervisory relationship, and, as a consequence, offset
      limited formal SUD training.

PMID- 25061264
TI  - Cardiopulmonary exercise capacity and preoperative markers of inflammation.
AB  - Explanatory mechanisms for the association between poor exercise capacity and
      infections following surgery are underexplored. We hypothesized that aerobic
      fitness-assessed by cardiopulmonary exercise testing (CPET)-would be associated
      with circulating inflammatory markers, as quantified by the neutrophil-lymphocyte
      ratio (NLR) and monocyte subsets. The association between cardiopulmonary reserve
      and inflammation was tested by multivariable regression analysis with covariates
      including anaerobic threshold (AT) and malignancy. In a first cohort of 240
      colorectal patients, AT was identified as the sole factor associated with higher
      NLR (P = 0.03) and absolute and relative lymphopenia (P = 0.01). Preoperative
      leukocyte subsets and monocyte CD14(+) expression (downregulated by endotoxin and
      indicative of chronic inflammation) were also assessed in two further cohorts of
      age-matched elective gastrointestinal and orthopaedic surgical patients. Monocyte
      CD14(+) expression was lower in gastrointestinal patients (n = 43) compared to
      age-matched orthopaedic patients (n = 31). The circulating CD14(+)CD16(-)
      monocyte subset was reduced in patients with low cardiopulmonary reserve. Poor
      exercise capacity in patients without a diagnosis of heart failure is
      independently associated with markers of inflammation. These observations suggest
      that preoperative inflammation associated with impaired cardiorespiratory
      performance may contribute to the pathophysiology of postoperative outcome. 

PMID- 25061266
TI  - The Association Between Peer and own Aggression is Moderated by the BDNF Val-met
      Polymorphism.
AB  - Peer antisocial behavior robustly predicts adolescents' own behavior but not all
      adolescents are equally vulnerable to their peers' influence and genetic factors
      may confer vulnerability. This study used data of n = 3081 adolescents from the
      Avon Longitudinal Study of Parents and Children (ALSPAC) to examine whether BDNF,
      a polymorphism that affects psychological functioning, moderates the association
      between affiliation with aggressive peers at age 10 and own aggression at age 15.
      A significant gene-environment interaction was found, where those who affiliated
      with aggressive peers in childhood showed increased risk for being aggressive in
      adolescence if they carried the BDNF met-met variant compared to val-val
      carriers. Our findings underline the importance of both biological and social
      factors for adolescent development.

PMID- 25061267
TI  - Prospective, randomized, contralateral eye comparison of tetracaine and
      proparacaine for pain control in laser in situ keratomileusis and photorefractive
      keratectomy.
AB  - BACKGROUND: Tetracaine and proparacaine are two of the most commonly used
      medications for providing topical anesthesia in laser in situ keratomileusis
      (LASIK) and photorefractive keratectomy (PRK). These agents have not been
      previously compared in a prospective manner to determine their efficacy in these
      settings. METHODS: This prospective, single-masked, randomized study comprised
      256 eyes from 128 consecutive patients being treated with LASIK or PRK who were
      randomized to receive tetracaine in one eye and proparacaine in the other. The
      patients were blinded as to which anesthetic agent was used in each eye. Pain
      levels were graded on a 0-10 scale, and were assessed upon instillation, during
      surgery, immediately postoperatively, 30 minutes postoperatively, overnight, and
      on postoperative day 1. Patients were asked 30 minutes after surgery which
      anesthetic agent they would choose. RESULTS: Both anesthetic agents resulted in
      diminished amounts of subjective pain in patients undergoing LASIK and PRK.
      Tetracaine caused significantly more pain upon instillation than proparacaine for
      both LASIK and PRK patients. LASIK patients noted significantly less pain 30
      minutes after surgery when treated with tetracaine. Significantly more LASIK
      patients preferred the eye treated with tetracaine. These differences were not
      present in the PRK group. CONCLUSION: Both tetracaine and proparacaine are
      effective methods of topical anesthesia in LASIK and PRK. Tetracaine caused
      significantly more pain upon instillation in all patients, but resulted in
      greater analgesia 30 minutes after surgery in the LASIK group. Patients in the
      LASIK group expressed a preference for tetracaine over proparacaine. There was no
      significant drop preference among PRK patients.

PMID- 25061268
TI  - Intensity of side effects of topical glaucoma medication and its influence on
      adherence behavior in patients with glaucoma.
AB  - BACKGROUND: The aim of this study was to investigate the intensity of side
      effects that patients attribute to their topical glaucoma medication and their
      relationship to adherence behavior. METHODS: This was a questionnaire-based study
      of 123 glaucoma patients at a university eye clinic in Erlangen, Germany. An
      initial questionnaire asked about patient demographic data, the treatment plan,
      and intensity of side effects, and included Adherence to Refills and Medication
      Scale 2 (ARMS2) and visual analog scale (VAS-AD) scores. In a follow-up
      questionnaire, the treatment plan, intensity of side effects, ARMS2, and VAS-AD
      were reanalyzed. RESULTS: Most patients reported having few side effects,
      although only 20% said that they had no symptoms suggestive of side effects at
      all. The patients showed good adherence behavior on both the ARMS2 and VAS-AD
      scores, which were stable over time. The intensity of side effects experienced in
      the previous 7 days did not correlate with adherence scores and had no predictive
      value for adherence. CONCLUSION: This study could not detect any significant
      influence of the subjectively experienced intensity of side effects on patients'
      adherence behavior. However, we believe that a simple and clear treatment plan
      with few side effects is still preferred by most patients.

PMID- 25061269
TI  - Factors affecting the use of antioxidant supplements in patients with late AMD.
AB  - BACKGROUND: The purpose of this study was to assess the use of oral antioxidant
      supplements in patients with late age-related macular degeneration (AMD) and to
      identify influencing factors that may affect the use of such supplements.
      METHODS: The study included 47 patients with late AMD. Using a questionnaire, the
      patients were asked for their demographic, ophthalmologic, and systemic data,
      their source of recommendation of antioxidant use for AMD, and/or their reasons
      for nonuse. The demographic, ophthalmologic, and systemic information was
      correlated with use or nonuse of oral antioxidant supplements for AMD. RESULTS:
      Sixty-eight percent (32/47) of patients took antioxidant supplements for AMD and
      32% (15/47) of patients did not. There were no statistically significant
      differences in demographic, ophthalmologic, and systemic parameters between
      patients with late AMD who used supplements and those who did not. Two thirds of
      patients with late AMD (66%, 31/47) reported being recommended oral antioxidant
      supplements for AMD by their ophthalmologist. Patients who did not use
      antioxidant supplements either did not obtain any recommendation or did not
      believe in their benefits. CONCLUSION: This study shows that most patients with
      late AMD use antioxidant supplements despite the recommendation to do so being
      missing in the Age-Related Eye Disease Study. Our study emphasizes the importance
      of seeking further therapeutic options for patients with late AMD.

PMID- 25061270
TI  - Assessment of beta-zone peripapillary atrophy by optical coherence tomography and
      scanning laser ophthalmoscopy imaging in glaucoma patients.
AB  - PURPOSE: To assess beta-zone peripapillary atrophy (beta-PPA) using spectral
      domain optical coherence tomography (SD-OCT), scanning laser ophthalmoscopy
      (SLO), and fundus auto-fluorescence (FAF) imaging in patients with primary open
      angle glaucoma with advanced glaucomatous visual field defects. METHODS: A
      consecutive, prospective series of 82 study eyes with primary open-angle glaucoma
      were included in this study. All study participants underwent a full ophthalmic
      examination followed by SD-OCT, wide-field SLO, and FAF imaging of the optic
      nerve head and the peripapillary region. RESULTS: Eighty-four glaucomatous eyes
      were included in our prospective study. Correlation analyses for horizontally and
      vertically obtained beta-PPA for all three imaging modalities (color SLO, FAF,
      and SD-OCT) revealed highest correlations between FAF and color SLO (Pearson
      correlation coefficient: 0.904 [P<0.001] for horizontal beta-PPA and 0.786
      [P<0.001] for vertical beta-PPA). Bland-Altman plotting revealed highest
      agreements between color SLO and FAF, with -2.1 pixels +/-1.96 standard deviation
      (SD) for horizontal beta-PPA, SD: 10.5 pixels and 2.4 pixels +/-1.96 SD for
      vertical beta-PPA. CONCLUSION: beta-PPA can be assessed using en-face SLO and
      cross-sectional SD-OCT imaging. Correlation analyses revealed highest
      correlations between color SLO and FAF imaging, while correlations between SLO
      and SD-OCT were weak. A more precise structural definition of beta-PPA is needed.

PMID- 25061271
TI  - Efficacy and safety of benzalkonium chloride-free fixed-dose combination of
      latanoprost and timolol in patients with open-angle glaucoma or ocular
      hypertension.
AB  - BACKGROUND: Benzalkonium chloride (BAK) is a common preservative in topical
      ocular preparations; however, prolonged use may lead to deleterious effects on
      the ocular surface, affecting quality of life and reducing adherence to treatment
      and overall outcomes. This study compared the intraocular pressure (IOP)-lowering
      efficacy and safety of a novel once-daily, BAK-free, fixed-dose combination of
      latanoprost plus timolol with latanoprost or timolol administered as monotherapy
      or concomitantly. METHODS: This was a 6-week, randomized, open-label, parallel
      group, active-controlled study in patients aged >=18 years with open-angle
      glaucoma or ocular hypertension. A total of 227 patients were randomized to
      either a once-daily, BAK-free, fixed-dose combination of latanoprost
      0.005%/timolol 0.5% ophthalmic solution or concomitant administration of once
      daily latanoprost 0.005% plus twice-daily timolol 0.5% or once-daily latanoprost
      0.005% monotherapy, or twice-daily timolol 0.5% monotherapy. Efficacy end points
      were assessed at three time points on visits at weeks 1, 2, 4, and 6 versus
      baseline. RESULTS: The IOP-lowering efficacy of the fixed-dose combination of
      latanoprost/timolol was similar to that of latanoprost plus timolol administered
      concomitantly at all time points (mean IOP difference and 95% confidence interval
      within +/-1.5 mmHg; P=0.4223 to P=0.9981). The fixed-dose combination of
      latanoprost/timolol demonstrated significantly better IOP-lowering efficacy than
      timolol monotherapy at all time points (P=0.001 to P<0.0001) and significantly
      better IOP-lowering efficacy than latanoprost monotherapy at all time points.
      Responder rates on at least one time point and on at least two time points with
      fixed-dose combination latanoprost/timolol were similar to those with concomitant
      latanoprost plus timolol (85.5% versus 82.1%, P=0.6360; 78.2% versus 75%,
      P=0.6923), but significantly better than either latanoprost or timolol
      monotherapy (68.5%, P=0.0355; 55.4%, P=0.0005; 57.4%, P=0.0202; and 46.4%,
      P=0.0006, respectively). No significant differences in ocular and nonocular
      treatment-emergent adverse events were found between the treatment groups.
      CONCLUSION: A BAK-free, fixed-dose combination of latanoprost 0.005%/timolol 0.5%
      was as effective and well tolerated as concomitant latanoprost and timolol for
      treatment of elevated IOP in patients with open-angle glaucoma or ocular
      hypertension.

PMID- 25061272
TI  - Efficacy of intravitreal dexamethasone implant for prostaglandin-induced
      refractory pseudophakic cystoid macular edema: case report and review of the
      literature.
AB  - BACKGROUND: Macular edema is a known complication even after uneventful cataract
      surgery. The chronic use of prostaglandin analogs is a risk factor for the
      development of pseudophakic cystoid macular edema (CME). Nonsteroidal anti
      inflammatory drugs (NSAIDs) are considered first-line therapy but refractory
      postsurgical CME represents a therapeutic challenge, as there is not an evidence
      based treatment. OBJECTIVE: To report the use of a single implant of intravitreal
      dexamethasone for tafluprost-associated pseudophakic CME refractory to NSAIDs and
      to sub-Tenon's corticosteroid injections. CASE REPORT: A 64-year-old female with
      ocular hypertension treated with tafluprost experienced decreased vision (visual
      acuity 20/60) and metamorphopsia 2 months after uneventful cataract extraction.
      Spectral domain optical coherence tomography (SD-OCT) revealed CME. After 1 month
      of topical and oral NSAIDs, CME was still evident on SD-OCT (visual acuity
      20/50). Two sub-Tenon's betamethasone injections were performed at a 2-week
      interval. As CME was still present, 2 months after the diagnosis of CME (visual
      acuity 20/40), the patient underwent a single dexamethasone intravitreal implant.
      One month later, macular appearance was normal, and visual acuity increased to
      20/30. This result was maintained throughout the 6 months of follow-up.
      CONCLUSION: In this report, a single implant of intravitreal dexamethasone
      successfully treated pseudophakic CME associated with the use of prostaglandin
      analogs unresponsive to NSAIDs and sub-Tenon's betamethasone. The results of this
      report need to be corroborated by powered, prospective, randomized trials. The
      need for repeated treatments as well as the retreatment interval in patients
      requiring more than a single injection are issues still needing further
      investigations.

PMID- 25061273
TI  - A 6-year-old girl with ectopic cilia and hypochromic nevus.
AB  - Ectopic cilia are rare in humans. We report a 6-year-old girl with typical
      characteristics of ectopic cilia as described in the rare cases reported in the
      literature, in association with cutaneous lesions that appeared to be hypochromic
      nevi. This framework could be a different clinical presentation of ectopic cilia.

PMID- 25061274
TI  - Ocular alignment and refraction in preterm children at 1 and 6 years old.
AB  - PURPOSE: To investigate cycloplegic refraction and ocular alignment in a
      population of preterm children at 1 and 6 years old. PATIENTS AND METHODS: We
      included 261 preterm infants with a birth weight <=1,500 g and a gestational age
      <=32 weeks; there were 217 preterm infants (group 1), 28 preterm infants with
      mild retinopathy of prematurity (ROP) (group 2), and 16 preterm infants affected
      by severe ROP (group 3). Each patient underwent retinoscopy, ocular alignment
      assessment, and fundus examination at 1 and 6 years old. RESULTS: The prevalence
      of refractive errors and ocular alignment abnormalities at 1 year old in groups 2
      and 3 compared to group 1 were, respectively (P<0.05): myopia 18% and 40.6%
      versus 6.9%; hyperopia 28.6% and 22% versus 39.2%; astigmatism 53.4% and 37.4%
      versus 53.9%; and strabismus 12.5% and 38% versus 5.3%. At 6 years old, they
      were, respectively (P<0.05): myopia 10.8% and 28.4% versus 7.4%; hyperopia 48.3%
      and 40.5% versus 62%; astigmatism 40.9% and 31.1% versus 30.6%; and strabismus
      25% and 56.25% versus 11.5%. CONCLUSION: At 6 years old, we observed increased
      rates of both hyperopia and strabismus in all groups compared to 1-year-old
      children. In preterm children with mild and severe ROP, we recorded increased
      rates of myopia and strabismus versus preterm children without ROP, and the risk
      of developing these disorders increased significantly with ROP severity.
      Astigmatism at 1 year old is not predictive of further development during growth.
      Patients born prematurely should be informed of the possible risks of ocular
      alterations due to refractive and ocular component changes.

PMID- 25061275
TI  - Efficacy and safety of switching to latanoprost 0.005%-timolol maleate 0.5% fixed
      combination eyedrops from an unfixed combination for 36 months.
AB  - PURPOSE: We prospectively investigated the intraocular pressure (IOP)-reducing
      effect, the visual field-maintenance effect, and the adverse reactions caused by
      administration of latanoprost/timolol maleate fixed-combination eyedrops for 3
      years. SUBJECTS AND METHODS: The subjects were 162 patients (162 eyes) with
      glaucoma or ocular hypotension who were using latanoprost and timolol maleate
      eyedrops concomitantly. The latanoprost and timolol maleate eyedrop regimen was
      discontinued without any washout period and subsequently changed to a latanoprost
      timolol maleate fixed-combination eyedrop regimen. IOP values before the change
      and at 6, 12, 18, 24, 30, and 36 months after the change were measured and
      compared. The Humphrey visual field test was conducted before the change and at
      12, 24, and 36 months after the change, and mean-deviation values were compared.
      Adverse reactions were assessed at every checkup. RESULTS: The IOPs before the
      change and at 6-36 months after the change were 15.2+/-3.3 mmHg and 14.3-15.2
      mmHg, respectively, and a significant decrease was observed at 36 months after
      the change (P<0.01). Mean-deviation values before the change and at 12-36 months
      after the change were -9.11+/-6.94 dB and -10.08 to -9.22 dB, respectively, and
      these values were not significantly different (P=0.2148). Within the 36-month
      period, the eyedrops were discontinued because of insufficient IOP decrease in 33
      cases (20.4%) and adverse reactions in eleven cases (6.8%). CONCLUSION: IOP and
      the visual field were maintained for 3 years when a latanoprost and timolol
      maleate eyedrop regimen was changed to a latanoprost-timolol maleate fixed
      combination eyedrop regimen. However, administration of the latanoprost-timolol
      maleate fixed-combination eyedrops was discontinued in approximately 27% of cases
      because of insufficient IOP decrease and adverse reactions.

PMID- 25061276
TI  - Management of mydriasis and pain in cataract and intraocular lens surgery: review
      of current medications and future directions.
AB  - The maintenance of mydriasis and the control of postoperative pain and
      inflammation are critical to the safety and success of cataract and intraocular
      lens replacement surgery. Appropriate mydriasis is usually achieved by topical
      and/or intracameral administration of anticholinergic agents, sympathomimetic
      agents, or both, with the most commonly used being cyclopentolate, tropicamide,
      and phenylephrine. Ocular inflammation is common after cataract surgery. Topical
      steroids and nonsteroidal anti-inflammatory drugs are widely used because they
      have been proved effective to control postsurgical inflammation and decrease
      pain. Topical nonsteroidal anti-inflammatory drugs have also been shown to help
      maintain dilation. However, use of multiple preoperative drops for pupil
      dilation, inflammation, and pain control have been shown to be time consuming,
      resulting in delays to the operating room, and they cause dissatisfaction among
      perioperative personnel; their use can also be associated with systemic side
      effects. Therefore, ophthalmologists have been in search of new options to
      streamline this process. This article will review the current medications
      commonly used for intraoperative mydriasis, as well as pain and inflammation
      control. In addition, a new combination of ketorolac, an anti-inflammatory agent,
      and phenylephrine, a mydriatic agent has recently been designed to maintain
      intraoperative mydriasis and to reduce postoperative pain and irritation from
      intraocular lens replacement surgery. Two Phase III clinical trials evaluating
      this combination have demonstrated statistically significant differences when
      compared to placebo in maintaining intraoperative mydriasis (P<0.00001) and in
      reducing pain in the early postoperative period (P=0.0002). This medication may
      be of benefit for use in cataract and lens replacement surgery in the near
      future. 

PMID- 25061278
TI  - Virologic breakthrough in a patient with chronic hepatitis B by combination
      treatment with tenofovir disoproxil fumarate and entecavir.
AB  - Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus
      (HBV) patients in the USA and Europe. No confirmed report of resistance selection
      during treatment with TDF in treatment-naive and nucleoside/nucleotide analog
      treated chronic hepatitis B patients has yet been reported. Here, we report for
      the first time a patient with chronic hepatitis B and cirrhosis who emerged with
      virologic breakthrough during combination therapy with TDF and entecavir (ETV),
      against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e
      antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously
      followed by TDF and ETV combination therapy, because her HBV DNA levels had been
      >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions
      of the reverse transcriptase (rt) gene, rtL180M, rtT184I/M, and rtM204V, were
      detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and
      remained at this level until 31 months of combination therapy, when it again
      began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V
      emerged and were associated with an increase in serum HBV DNA at virologic
      breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the
      potential to induce virologic breakthrough and resistance, and careful follow-up
      should be carried out. 

PMID- 25061277
TI  - Clinical effectiveness and safety of montelukast in asthma. What are the
      conclusions from clinical trials and meta-analyses?
AB  - Asthma is a common childhood atopic disease associated with chronicity and
      impaired quality of life. As there is no cure for this disease, treatment relies
      on avoidance of triggers such as food and aeroallergens, the use of inhaled
      bronchodilators/corticosteroids and antiallergic or immunomodulating therapies.
      Inhaled corticosteroids (ICSs) and bronchodilators have been the mainstay.
      However, in Asia, myths and fallacies regarding Western medicine and
      corticosteroids are prevalent and lead to nonadherence to treatment. Also, use of
      traditional and proprietary herbal medicines is popular. In the past decades, a
      novel class of nonsteroidal immunomodulating montelukasts has become available.
      This article reviews the evidence for the effectiveness and clinical efficacy of
      these medications. A number of randomized and controlled trials have been
      performed over the years. The majority of studies confirm the usefulness of
      montelukast as monotherapy and add-on therapy to ICS in mild to moderate
      childhood asthma across all age groups. ICSs are generally superior to
      montelukasts for asthma management. However, montelukast has a place in the
      treatment of young children with viral-triggered wheezing diseases, exercise
      induced asthma, and in children whose parents are steroid-phobic and find ICS
      unacceptable. 

PMID- 25061279
TI  - Treatment of pulmonary hypertension in idiopathic pulmonary fibrosis: shortfall
      in efficacy or trial design?
AB  - Idiopathic pulmonary fibrosis (IPF) is a disease that carries a high mortality.
      Pulmonary hypertension (PH) frequently complicates the course of patients with
      IPF and is associated with significantly worse outcomes. Whether PH is a
      surrogate or driver of these worse outcomes remains unanswered, but the presence
      of PH represents an attractive target for therapy. This review delves into the
      various pulmonary vasoactive agents that have been subjected to study in IPF, the
      pitfalls of some of these prior studies, and attempts to lay a foundation for
      future study designs targeting PH in IPF. 

PMID- 25061281
TI  - Acceptance of orthodontic miniscrews as temporary anchorage devices.
AB  - OBJECTIVE: To study the patient's acceptance, expectation, and experience of pain
      with orthodontic temporary miniscrews. METHODS: Questionnaires were distributed
      to 165 potential temporary orthodontic miniscrew recipients or their parents.
      Using the numeric rating scale, patients who received miniscrews as part of their
      orthodontic treatment were also asked to rate the pain or discomfort experience
      after miniscrew placement. RESULTS: A total of 165 subjects completed the first
      set of questions. There was a significant relationship between level of education
      and prior knowledge about orthodontic miniscrews (P=0.029). Even though only
      12.7% had heard about miniscrews, 82.4% agreed to have miniscrews placed to
      facilitate orthodontic tooth movement. Eighty-three subjects who needed
      miniscrews as part of their orthodontic treatment completed two more sets of
      questions after 6 and 24 hours of miniscrew insertion. After 6 hours of miniscrew
      insertion, there was a significant difference in pain perception between men
      (mean =2.6+/-2.2) and women (mean =2.1+/-1.5; P=0.03). After 24 hours, there was
      no difference between men (0.2+/-0.4) and women (0.2+/-0.5; P>0.05).
      Postplacement, 32.5% did not require any pain medication, while 59.1% required a
      single dose and only 8.4% required two doses. A total of 76 patients (91.6%) said
      that they would recommend this procedure. CONCLUSION: Patients do accept
      miniscrew as a treatment option in orthodontics. Postoperative pain is
      significantly low. The acceptance of miniscrews was not related to patient's
      previous knowledge of the device, and patients preferred miniscrews to
      extractions.

PMID- 25061282
TI  - Guidelines for adapting cognitive stimulation therapy to other cultures.
AB  - Cognitive stimulation therapy (CST) has been shown to be an useful and cost
      effective intervention that increases cognition and quality of life of people
      with mild to moderate dementia. It is increasing in popularity in the UK and
      worldwide, and a number of research teams have examined its effectiveness in
      other contexts and cultures. However, it is necessary to develop clear evidence
      based guidelines for cultural modification of the intervention. This article
      describes a community-based developmental approach to adapt CST to different
      cultures, following the five phases of the formative method for adapting
      psychotherapy (FMAP), an approach that involves collaborating with service users
      as a first step to generate and support ideas for therapy adaptation. Examples
      based on clinical and practical experience are presented, along with suggestions
      for applying these changes in different cultural contexts. 

PMID- 25061280
TI  - New approaches to the management of schizophrenia: focus on aberrant hippocampal
      drive of dopamine pathways.
AB  - Schizophrenia is a disease affecting up to 1% of the population. Current
      therapies are based on the efficacy of chlorpromazine, discovered over 50 years
      ago. These drugs block dopamine D2-like receptors and are effective at primarily
      treating positive symptoms in a subset of patients. Unfortunately, current
      therapies are far from adequate, and novel treatments require a better
      understanding of disease pathophysiology. Here we review the dopamine, gamma
      aminobutyric acid (GABA), and glutamate hypotheses of schizophrenia and describe
      a pathway whereby a loss of inhibitory signaling in ventral regions of the
      hippocampus actually drives a dopamine hyperfunction. Moreover, we discuss novel
      therapeutic approaches aimed at attenuating ventral hippocampal activity in a
      preclinical model of schizophrenia, namely the MAM GD17 rat. Specifically,
      pharmacological (allosteric modulators of the alpha5 GABAA receptor),
      neurosurgical (deep brain stimulation), and cell-based (GABAergic precursor
      transplants) therapies are discussed. By better understanding the underlying
      circuit level dysfunctions in schizophrenia, novel treatments can be advanced
      that may provide better efficacy and a superior side effect profile to
      conventional antipsychotic medications. 

PMID- 25061283
TI  - Appropriate blood pressure for the "old-old" (85 years and older).

PMID- 25061284
TI  - Type 2 diabetes as a risk factor for cognitive impairment: current insights.
AB  - Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction and
      dementia in the elderly. T2DM has been thought to be associated with vascular
      diseases, eventually leading to vascular dementia, but recent studies have
      established that T2DM is also associated with Alzheimer's disease (AD). With the
      increase in the number of elderly individuals with T2DM, the number of diabetic
      patients with cognitive dysfunction has been increasing. T2DM may accelerate AD
      associated pathologies through insulin resistance. Vascular pathologies may also
      be associated with cognitive dysfunction and dementia in T2DM subjects. Several
      other mechanisms also seem to be involved in T2DM-related cognitive dysfunction.
      More investigations to clarify the association of T2DM with cognitive impairment
      are warranted. These investigations may help to increase our understanding of AD
      and open a new door to the development of therapeutics. Recent pharmaceutical
      advancement in T2DM treatment has resulted in the availability of a wide range of
      antidiabetics. Some evidence has suggested that antidiabetic therapies help to
      prevent cognitive dysfunction. At present, however, the optimal level of blood
      glucose control and the best combination of medications to achieve it in terms of
      cognitive preservation have not been established. More investigation is
      warranted. Cognitive dysfunction is an emerging new complication of T2DM that
      requires further study. 

PMID- 25061285
TI  - Estrogen receptor alpha gene polymorphisms and risk of Alzheimer's disease:
      evidence from a meta-analysis.
AB  - OBJECTIVE: Human estrogen receptor alpha (ESR1), a member of the nuclear receptor
      superfamily of ligand-activated transcription factors, is one of the key
      mediators of hormonal response in estrogen-sensitive tissues. Accumulating
      evidence has demonstrated that two of the most widely studied single-nucleotide
      polymorphisms in ESR1 - PvuII (T/C, rs223493) and Xbal (A/G, rs9340799) - are
      possibly associated with Alzheimer's disease (AD). However, individual study
      results are still controversial. MATERIALS AND METHODS: We searched PubMed,
      Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National
      Knowledge Infrastructure databases for eligible studies assessing the association
      of ESR1 polymorphisms and AD risk (last search performed in November 2013).
      Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was
      conducted to evaluate the association between ESR1 polymorphisms and
      susceptibility to AD. RESULTS: The results indicated that a significant
      association was found between the ESR1 PvuII polymorphism and AD risk in
      Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence
      interval [CI] 1.02-1.28, P=0.03; CT versus TT, OR 1.16, 95% CI 1.02-1.31,
      P=0.02), whereas no evidence of association was found in Asian populations.
      Nevertheless, we did not find any significant association between the ESR1 XbaI
      polymorphism and AD risk for any model in Caucasian and Asian populations (all
      P>0.05). CONCLUSION: Based on this meta-analysis, we conclude that the ESR1 PvuII
      polymorphism might be a risk factor in AD development in Caucasian populations,
      not in Asian populations. Further confirmation is needed from better-designed and
      larger studies.

PMID- 25061286
TI  - Extent and prevalence of cognitive dysfunction in chronic obstructive pulmonary
      disease, chronic non-obstructive bronchitis, and in asymptomatic smokers,
      compared to normal reference values.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) can affect cognition.
      The effects of other less severe chronic airway disorders on cognition remain to
      be clarified. This study aimed to measure and compare cognitive deterioration in
      subjects with COPD, subjects with chronic non-obstructive bronchitis (CNOB), and
      asymptomatic smokers (AS), and to relate the corresponding prevalence to several
      demographic and clinical variables and to normal reference values. METHODS: Four
      hundred and two subjects (COPD n=229, CNOB n=127, and AS n=46) of comparable age
      were included in the study. Cognitive impairment was assessed using the Mini
      Mental Status test, the Clock Drawing test, and the Trail Making test A and B.
      RESULTS: The extent and prevalence of cognitive deterioration was greater in COPD
      subjects, followed by CNOB subjects and AS (P<0.001). The Medical Research
      Council and COPD Assessment test scores, forced expiratory volume in the first
      second predicted, and arterial partial pressure of O2 and of CO2 were related to
      the extent and the prevalence of cognitive deterioration. COPD subjects, CNOB
      subjects, and AS aged 40-69 years showed the greatest cognitive impairment
      (P<0.01 compared to normal values). This was particularly clear in COPD subjects.
      CONCLUSION: Cognitive impairment may start at the early stages of chronic airway
      damage and progress with a worsening of the respiratory condition. Indeed, the
      greatest cognitive deterioration was seen in COPD subjects. Cognition impairment
      may contribute to explaining the insufficient adherence to therapeutic plans and
      strategies, and the increasing social costs in respiratory subjects.

PMID- 25061288
TI  - Differential pharmacology and clinical utility of emerging combination treatments
      in the management of COPD--role of umeclidinium/vilanterol.
AB  - Chronic obstructive pulmonary disease (COPD) is a preventable and treatable
      disease characterized by airflow limitation that is not fully reversible.
      Bronchodilator therapy is the cornerstone in COPD treatment. Bronchodilation in
      COPD is mainly achieved via administration of long- and ultralong-acting beta2
      agonists and with long-acting muscarinic antagonists. New combinations of
      bronchodilators with dual-acting muscarinic antagonist and beta2-agonist
      properties have been licensed, and others are currently being developed with the
      aim of achieving once-daily dosing, and therefore may improve the likelihood of
      treatment compliance. These combination bronchodilators include glycopyrronium
      bromide/indacaterol maleate, umeclidinium (UMEC) bromide/vilanterol trifenatate
      (VI), aclidinium bromide/formoterol and tiotropium bromide/olodaterol (Boehringer
      Ingelheim, Germany). This review will focus mainly on studies and clinical trials
      involving the novel fixed-dose combination of UMEC/VI at doses of 125/25 MUg and
      62.5/25 MUg in patients with COPD. Data from large clinical trials involving more
      than 4,500 COPD patients indicate that UMEC/VI is an effective once-daily
      treatment in COPD with improved pulmonary function. Future studies assessing the
      impact of this combination on exacerbations, delay in disease progression, and
      health status in patients with COPD are warranted. 

PMID- 25061289
TI  - A new approach for noninvasive transdermal determination of blood uric acid
      levels.
AB  - The aims of this study were to investigate the most effective combination of
      physical forces from laser, electroporation, and reverse iontophoresis for
      noninvasive transdermal extraction of uric acid, and to develop a highly
      sensitive uric acid biosensor (UAB) for quantifying the uric acid extracted. It
      is believed that the combination of these physical forces has additional benefits
      for extraction of molecules other than uric acid from human skin. A diffusion
      cell with porcine skin was used to investigate the most effective combination of
      these physical forces. UABs coated with ZnO2 nanoparticles and constructed in an
      array configuration were developed in this study. The results showed that a
      combination of laser (0.7 W), electroporation (100 V/cm(2)), and reverse
      iontophoresis (0.5 mA/cm(2)) was the most effective and significantly enhanced
      transdermal extraction of uric acid. A custom-designed UAB coated with ZnO2
      nanoparticles and constructed in a 1*3 array configuration (UAB-1*3-ZnO2)
      demonstrated enough sensitivity (9.4 MUA/mM) for quantifying uric acid extracted
      by the combined physical forces of laser, electroporation, and RI. A good linear
      relationship (R(2)=0.894) was demonstrated to exist between the concentration of
      uric acid (0.2-0.8 mM) inside the diffusion cell and the current response of the
      UAB-1*3-ZnO2. In conclusion, a new approach to noninvasive transdermal extraction
      and quantification of uric acid has been established.

PMID- 25061290
TI  - Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle
      dispersion for enhancement of stability and anticancer activity.
AB  - Despite the promising anticancer potential of curcumin, its therapeutic
      application has been limited, owing to its poor solubility, bioavailability, and
      chemical fragility. Therefore, various formulation approaches have been attempted
      to address these problems. In this study, we entrapped curcumin into monoolein
      (MO)-based liquid crystalline nanoparticles (LCNs) and evaluated the
      physicochemical properties and anticancer activity of the LCN dispersion. The
      results revealed that particles in the curcumin-loaded LCN dispersion were
      discrete and monodispersed, and that the entrapment efficiency was almost 100%.
      The stability of curcumin in the dispersion was surprisingly enhanced (about 75%
      of the curcumin survived after 45 days of storage at 40 degrees C), and the in
      vitro release of curcumin was sustained (10% or less over 15 days). Fluorescence
      activated cell sorting (FACS) analysis using a human colon cancer cell line
      (HCT116) exhibited 99.1% fluorescence gating for 5 MUM curcumin-loaded LCN
      dispersion compared to 1.36% for the same concentration of the drug in dimethyl
      sulfoxide (DMSO), indicating markedly enhanced cellular uptake. Consistent with
      the enhanced cellular uptake of curcumin-loaded LCNs, anticancer activity and
      cell cycle studies demonstrated apoptosis induction when the cells were treated
      with the LCN dispersion; however, there was neither noticeable cell death nor
      significant changes in the cell cycle for the same concentration of the drug in
      DMSO. In conclusion, entrapping curcumin into MO-based LCNs may provide, in the
      future, a strategy for overcoming the hurdles associated with both the stability
      and cellular uptake issues of the drug in the treatment of various cancers. 

PMID- 25061291
TI  - Anticancer nanodelivery system with controlled release property based on
      protocatechuate-zinc layered hydroxide nanohybrid.
AB  - BACKGROUND: We characterize a novel nanocomposite that acts as an efficient
      anticancer agent. METHODS: This nanocomposite consists of zinc layered hydroxide
      intercalated with protocatechuate (an anionic form of protocatechuic acid), that
      has been synthesized using a direct method with zinc oxide and protocatechuic
      acid as precursors. RESULTS: The resulting protocatechuic acid nanocomposite
      (PAN) showed a basal spacing of 12.7 A, indicating that protocatechuate was
      intercalated in a monolayer arrangement, with an angle of 54 degrees  from the Z
      axis between the interlayers of the zinc layered hydroxide, and an estimated drug
      loading of about 35.7%. PAN exhibited the properties of a mesoporous type
      material, with greatly enhanced thermal stability of protocatechuate as compared
      to its free counterpart. The presence of protocatechuate in the interlayers of
      the zinc layered hydroxide was further supported by Fourier transform infrared
      spectroscopy. Protocatechuate was released from PAN in a slow and sustained
      manner. This mechanism of release was well represented by a pseudo-second order
      kinetics model. PAN has shown increased cytotoxicity compared to the free form of
      protocatechuic acid in all cancer cell lines tested. Tumor growth suppression was
      extensive, particularly in HepG2 and HT29 cell lines. CONCLUSION: PAN is suitable
      for use as a controlled release formulation, and our in vitro evidence indicates
      that PAN is an effective anticancer agent. PAN may have potential as a
      chemotherapeutic drug for human cancer.

PMID- 25061292
TI  - Chitosan gel containing polymeric nanocapsules: a new formulation for vaginal
      drug delivery.
AB  - The vaginal route of administration is an alternative for several treatments for
      either local or systemic pharmacological effects. However, the permanence of a
      drug in this route represents a challenge for formulation development that can be
      overcome by using nanoencapsulation and chitosan gel. Thus, this work aimed to
      evaluate the performance of chitosan hydrogels containing cationic and anionic
      acrylic-based nanocapsules (Eudragit RS 100 and Eudragit S 100, respectively)
      with Nile red as a model of lipophilic substance in the vaginal route of
      administration, as measured by increases in the residence time and the
      penetration of these formulations. Several formulations were prepared with
      increasing chitosan concentrations, and were analyzed in terms of pH and
      rheological behavior so that the most suitable formulation could be selected. The
      enhancement of the adhesion (tensile stress test and washability profile) and
      penetration (confocal laser scanning microscopy and extraction followed by
      quantification) properties of the formulations, when applied to porcine vaginal
      mucosa, were evaluated. The nanocapsule suspensions produced presented adequate
      properties: size of approximately 200 nm (polydispersity index of <=0.2); zeta
      potential around +10 mV for the cationic formulation and -10 mV for the anionic
      formulation; and pH values of 6.1+/-0.1 (Eudragit RS 100), 5.3+/-0.2 (Eudragit S
      100), 6.2+/-0.1 (Nile red loaded Eudragit RS 100), and 5.1+/-0.1 (Nile red loaded
      Eudragit S 100). The chitosan formulation presented suitable viscosity for
      vaginal application and acidic pH (approximately 4.5). The tensile stress test
      showed that both formulations containing polymeric nanocapsules presented higher
      mucoadhesion when compared with the formulation without nanocapsules. In the
      washability experiment, no significant differences were found between
      formulations. Confocal microscopy and fluorescence quantification after
      extraction from the mucosa showed higher penetration of Nile red when it was
      nanoencapsulated, particularly in cationic nanocapsules. The formulations
      developed based on chitosan gel vehicle at 2.5% weight/weight containing
      polymeric nanocapsules, especially the cationic nanocapsules, demonstrated
      applicability for the vaginal delivery of hydrophobic substances.

PMID- 25061294
TI  - Stepwise encapsulation and controlled two-stage release system for cis
      Diamminediiodoplatinum.
AB  - cis-Diamminediiodoplatinum (cis-DIDP) is a cisplatin-like anticancer drug with
      higher anticancer activity, but lower stability and price than cisplatin. In this
      study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared
      by an emulsion solvent evaporation method. The maximum drug loading capacity of
      cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation
      efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH
      =7.4) at 37.5 degrees C exhibited a unique two-stage process, which could prove
      beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol
      2-yl]-2, 5-diphenyltetrazolium bromide) assay results showed that cis-DIDP
      released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition
      activity than cis-DIDP that had not been loaded. 

PMID- 25061295
TI  - Novel gramicidin formulations in cationic lipid as broad-spectrum microbicidal
      agents.
AB  - Dioctadecyldimethylammonium bromide (DODAB) is an antimicrobial lipid that can be
      dispersed as large closed bilayers (LV) or bilayer disks (BF). Gramicidin (Gr) is
      an antimicrobial peptide assembling as channels in membranes and increasing their
      permeability towards cations. In mammalian cells, DODAB and Gr have the drawbacks
      of Gram-positive resistance and high toxicity, respectively. In this study, DODAB
      bilayers incorporating Gr showed good antimicrobial activity and low toxicity.
      Techniques employed were spectroscopy, photon correlation spectroscopy for sizing
      and evaluation of the surface potential at the shear plane, turbidimetric
      detection of dissipation of osmotic gradients in LV/Gr, determination of
      bacterial cell lysis, and counting of colony-forming units. There was
      quantitative incorporation of Gr and development of functional channels in LV. Gr
      increased the bilayer charge density in LV but did not affect the BF charge
      density, with localization of Gr at the BF borders. DODAB/Gr formulations
      substantially reduce Gr toxicity against eukaryotic cells and advantageously
      broaden the antimicrobial activity spectrum, effectively killing Escherichia coli
      and Staphylococcus aureus bacteria with occurrence of cell lysis. 

PMID- 25061293
TI  - Glial cell line-derived neurotrophic factor gene delivery via a polyethylene
      imine grafted chitosan carrier.
AB  - Parkinson's disease is known to result from the loss of dopaminergic neurons.
      Direct intracerebral injections of high doses of recombinant glial cell line
      derived neurotrophic factor (GDNF) have been shown to protect adult nigral
      dopaminergic neurons. Because GDNF does not cross the blood-brain barrier,
      intracerebral gene transfer is an ideal option. Chitosan (CHI) is a naturally
      derived material that has been used for gene transfer. However, the low water
      solubility often leads to decreased transfection efficiency. Grafting of highly
      water-soluble polyethylene imines (PEI) and polyethylene glycol onto polymers can
      increase their solubility. The purpose of this study was to design a non-viral
      gene carrier with improved water solubility as well as enhanced transfection
      efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800
      g/mol) of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI,
      respectively) by opening the epoxide ring of ethylene glycol diglycidyl ether (EX
      810). This modification resulted in a non-viral gene carrier with less
      cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid
      (DNA) polyplexes was significantly higher than either PEI1800-g-CHI/DNA or
      CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the
      polymer:DNA weight ratio of 10:1, which was 1.7-fold higher than the maximal GDNF
      expression of PEI1800-g-CHI/DNA. The low toxicity and high transfection
      efficiency of PEI600-g-CHI make it ideal for application to GDNF gene therapy,
      which has potential for the treatment of Parkinson's disease. 

PMID- 25061296
TI  - Novel flower-shaped albumin particles as controlled-release carriers for drugs to
      penetrate the round-window membrane.
AB  - Controlled-release carriers for local drug delivery have attracted increasing
      attention for inner-ear treatment recently. In this paper, flower-shaped bovine
      serum albumin (FBSA) particles were prepared by a modified desolvation method
      followed by glutaraldehyde or heat denaturation. The size of the FBSA particles
      varied from 10 MUm to 100 MUm, and most were 50-80 MUm. Heat-denatured FBSA
      particles have good cytocompatibility with a prolonged survival time for L929
      cells. The FBSA particles were utilized as carriers to investigate the release
      behaviors of the model drug - rhodamine B. Rhodamine B showed a sustained-release
      effect and penetrated the round-window membrane of guinea pigs. We also confirmed
      the attachment of FBSA particles onto the round-window membrane by microscopy.
      The FBSA particles, with good biocompatibility, drug-loading capacity, adhesive
      capability, and biodegradability, may have potential applications in the field of
      local drug delivery for inner-ear disease treatment. 

PMID- 25061297
TI  - MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for
      pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal cancer,
      characterized by a set of known mutations, invasive features, and aberrant
      microRNA expression that have been associated with hallmark malignant properties
      of PDAC. The lack of effective PDAC treatment options prompted us to investigate
      whether microRNAs would constitute promising therapeutic targets toward the
      generation of a gene therapy approach with clinical significance for this
      disease. In this work, we show that the developed human serum albumin-1-palmitoyl
      2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA
      oligonucleotides (+/-) (4/1) nanosystem exhibits the ability to efficiently
      deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR
      21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete
      abolishment of microRNA expression. Silencing of these microRNAs resulted in a
      significant increase in the levels of their targets. Moreover, the combination of
      microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug
      sunitinib resulted in a strong and synergistic antitumor effect, showing that
      this combined strategy could be of great importance for therapeutic application
      in PDAC. 

PMID- 25061299
TI  - Elucidating the role of free polycationic chains in polycation gene carriers by
      free chains of polyethylenimine or N,N,N-trimethyl chitosan plus a certain
      polyplex.
AB  - Polycations as gene carriers have attracted considerable attention over the past
      decade. Generally, polyplexes between polycations and deoxyribonucleic acid (DNA)
      are formed at low N/P ratios (the ratios of the numbers of nitrogen atoms in a
      polycation to the numbers of phosphorus atoms in DNA), but high transfection
      efficiency can only be obtained at much higher N/P ratios. Thus, many
      polycationic chains are still free in solution. In this study, we investigated
      the detailed functions of free polyethylenimine chains (PEI-F) and free N,N,N
      trimethyl chitosan chains (TMC-F) using the same polyplex, ie, TMC polyplex (TMC
      P), which has high stability in Dulbecco's Modified Eagle's Medium (DMEM).
      Meanwhile, PEI polyplex (PEI-P)/PEI-F was also evaluated rather than PEI-P/TMC-F
      because the stability of PEI-P is low in DMEM and, in the latter case, the TMC-F
      may replace the bound PEI chain in PEI-P to form TMC-P. The transfection results
      show that both TMC-F and PEI-F can significantly increase the transfection
      efficiency of TMC-P; however, PEI-F can upregulate the gene expression of TMC-P
      more efficiently than TMC-F. Further investigations on the endocytosis and
      intracellular trafficking show that PEI-P/PEI-F, TMC-P/PEI-F, and TMC-P/TMC-F
      exhibit similar cellular uptake efficiency. However, by shutting down the
      clathrin-mediated endocytosis or vacuolar proton pump, the transfection
      efficiency decreases in the order of PEI-P/PEI-F > TMC-P/PEI-F > TMC-P/TMC-F.
      These findings indicate that PEI-F and TMC-F may promote the transfection
      efficiency of the polyplex by affecting its cellular uptake pathway and
      intracellular trafficking. 

PMID- 25061298
TI  - Effect of nanostructured TiO2 crystal phase on photoinduced apoptosis of breast
      cancer epithelial cells.
AB  - PURPOSE: The use of nanoparticles has seen exponential growth in the area of
      health care, due to the unique physicochemical properties of nanomaterials that
      make them desirable for medical applications. The aim of this study was to
      examine the effects of crystal phase-nanostructured titanium dioxide particles on
      bioactivity/cytotoxicity in breast cancer epithelial cells. MATERIALS AND
      METHODS: Cultured Michigan Cancer Foundation (MCF)-7 and human breast
      adenocarcinoma (MDA-MB-468) breast cancer epithelial cells were exposed to
      ultraviolet A light (wavelength 350 nm) for 20 minutes in the presence of aqueous
      dispersions of two different nanostructured titanium dioxide (TiO2) crystal
      phases: anatase and an anatase-rutile mixture. Detailed characterization of each
      titanium dispersion was performed by dynamic light scattering. A 3-(4,5
      dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) colorimetric assay
      was employed to estimate the percentage of viable cells after each treatment.
      Western blot analysis of protein expression and characterization, as well as a
      deoxyribonucleic acid (DNA)-laddering assay, were used to detect cell apoptosis.
      RESULTS: Our results documented that 100% anatase TiO2 nanoparticles (110-130 nm)
      exhibited significantly higher cytotoxicity in the highly malignant MDA-MB-468
      cancer cells than anatase- rutile mixtures (75%/25%) with the same size. On the
      contrary, MCF-7 cells (characterized by low invasive properties) were not
      considerably affected. Exposure of MDA-MB-468 cells to pure anatase nanoparticles
      or anatase-rutile mixtures for 48 hours resulted in increased proapoptotic Bax
      expression, caspase-mediated poly(adenosine diphosphate ribose) polymerase (PARP)
      cleavage, DNA fragmentation, and programmed cell death/apoptosis. CONCLUSION: The
      obtained results indicated that pure anatase TiO2 nanoparticles exhibit superior
      cytotoxic effects compared to anatase-rutile mixtures of the same size. The
      molecular mechanism of TiO2 nanoparticle cytotoxicity involved increased Bax
      expression and caspase-mediated PARP inactivation, thus resulting in DNA
      fragmentation and cell apoptosis.

PMID- 25061300
TI  - Towards Horizon 2020: challenges and advances for clinical mental health research
      - outcome of an expert survey.
AB  - BACKGROUND: The size and increasing burden of disease due to mental disorders in
      Europe poses substantial challenges to its population and to the health policy of
      the European Union. This warrants a specific research agenda concerning clinical
      mental health research as one of the cornerstones of sustainable mental health
      research and health policy in Europe. The aim of this research was to identify
      the top priorities needed to address the main challenges in clinical research for
      mental disorders. METHODS: The research was conducted as an expert survey and
      expert panel discussion during a scientific workshop. RESULTS: Eighty-nine
      experts in clinical research and representing most European countries
      participated in this survey. Identified top priorities were the need for new
      intervention studies, understanding the diagnostic and therapeutic implications
      of mechanisms of disease, and research in the field of somatic-psychiatric
      comorbidity. The "subjectivity gap" between basic neuroscience research and
      clinical reality for patients with mental disorders is considered the main
      challenge in psychiatric research, suggesting that a shift in research paradigms
      is required. CONCLUSION: Innovations in clinical mental health research should
      bridge the gap between mechanisms underlying novel therapeutic interventions and
      the patient experience of mental disorder and, if present, somatic comorbidity.
      Clinical mental health research is relatively underfunded and should receive
      specific attention in Horizon 2020 funding programs.

PMID- 25061301
TI  - A failure to confirm the effectiveness of a brief group psychoeducational program
      for mothers of children with high-functioning pervasive developmental disorders:
      a randomized controlled pilot trial.
AB  - OBJECTIVE: The purpose of this study was to examine the effectiveness of group
      psychoeducation to relieve the psychological distress of mothers of children with
      high-functioning pervasive developmental disorders (HFPDD) and to improve the
      behaviors of the children. METHODS: Seventy-two mothers of preschool outpatients
      with HFPDD were randomly assigned to a four-session brief group psychoeducational
      program (GP). The sessions were held every second week in addition to the usual
      treatment (GP + treatment as usual [TAU] group), or to a TAU-alone group. The
      primary outcome was self-reported symptoms of maternal mental health as assessed
      using the 28-item General Health Questionnaire (GHQ-28) at 21 weeks post
      randomization (week 21). The GHQ-28 at the end of the intervention (week 7),
      Aberrant Behavior Checklist (ABC) for the behavior of the children, the Zarit
      Burden Interview (ZBI), and the Medical Outcomes Study 36-item Short Form Health
      Survey (SF-36) were carried out at weeks 7 and 21. We tested the group effects
      with the interaction between the intervention and the evaluation points. RESULTS:
      The GHQ-28 score at week 21 was significantly higher in the GP + TAU group as
      compared to that in the TAU-alone group, indicating a greater improvement in the
      TAU-alone group. There was no evidence that GP + TAU led to a greater improvement
      of maternal mental health than TAU-alone at week 7. Similarly, no evidence was
      obtained to indicate that GP + TAU led to a reduction in the ABC or ZBI scores by
      week 7 or 21. The adjusted scores for the RF (role emotional) and MH (mental
      health) subscales of the SF-36 at week 21 were also significantly lower in the GP
      + TAU group, indicating a similar tendency to that of the change of the GHQ-28
      score at week 21. CONCLUSION: The psychoeducational program did not alleviate
      maternal distress, aberrant behaviors of the children, or caregiver burden.

PMID- 25061303
TI  - COMT Val158Met, but not BDNF Val66Met, is associated with white matter
      abnormalities of the temporal lobe in patients with first-episode, treatment
      naive major depressive disorder: a diffusion tensor imaging study.
AB  - We investigated the association between the Val158Met polymorphism of the
      catechol-O-methyltransferase (COMT) gene, the Val66Met polymorphism of the brain
      derived neurotrophic factor (BDNF) gene, and white matter changes in patients
      with major depressive disorder (MDD) and healthy subjects using diffusion tensor
      imaging (DTI). We studied 30 patients with MDD (17 males and 13 females, with
      mean age +/- standard deviation [SD] =44+/-12 years) and 30 sex- and age-matched
      healthy controls (17 males and 13 females, aged 44+/-13 years). Using DTI
      analysis with a tract-based spatial statistics (TBSS) approach, we investigated
      the differences in fractional anisotropy, radial diffusivity, and axial
      diffusivity distribution among the three groups (patients with the COMT gene
      Val158Met, those with the BDNF gene Val66Met, and the healthy subjects). In a
      voxel-wise-based group comparison, we found significant decreases in fractional
      anisotropy and axial diffusivity within the temporal lobe white matter in the Met
      carriers with MDD compared with the controls (P<0.05). No correlations in
      fractional anisotropy, axial diffusivity, or radial diffusivity were observed
      between the MDD patients and the controls, either among those with the BDNF
      Val/Val genotype or among the BDNF Met-carriers. These results suggest an
      association between the COMT gene Val158Met and the white matter abnormalities
      found in the temporal lobe of patients with MDD. 

PMID- 25061302
TI  - Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment
      of pseudobulbar affect.
AB  - Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated
      with many neurological diseases, including amyotrophic lateral sclerosis,
      Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease, and
      traumatic brain injury. PBA is defined by involuntary and uncontrollable
      expressed emotion that is exaggerated and inappropriate, and also incongruent
      with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a
      combination product indicated for the treatment of PBA. The quinidine component
      of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of
      dextromethorphan to its active metabolite dextrorphan, thereby increasing
      dextromethorphan systemic bioavailability and driving the pharmacology toward
      that of the parent drug and away from adverse effects of the dextrorphan
      metabolite. Three published efficacy and safety studies support the use of DM/Q
      in the treatment of PBA; significant effects were seen on the primary end point,
      the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end
      points and quality of life. While concentration-effect relationships appear
      relatively weak for efficacy parameters, concentrations of DM/Q may have an
      impact on safety. Some special safety concerns exist with DM/Q, primarily because
      of the drug interaction and QT prolongation potential of the quinidine component.
      However, because concentrations of dextrorphan (which is responsible for many of
      the parent drug's side effects) and quinidine are lower than those observed in
      clinical practice with these drugs administered alone, some of the perceived
      safety issues may not be as relevant with this low dose combination product.
      However, since patients with PBA have a variety of other medical problems and are
      on numerous other medications, they may not tolerate DM/Q adverse effects, or may
      be at risk for drug interactions. Some caution is warranted when initiating DM/Q
      treatment, particularly in patients with underlying risk factors for torsade de
      pointes and in those receiving medications that may interact with DM/Q. 

PMID- 25061304
TI  - The predictive value of somatic and cognitive depressive symptoms for cytokine
      changes in patients with major depression.
AB  - CONTEXT: Elevated concentrations of proinflammatory cytokines have been
      hypothesized as an important factor in the pathophysiology of depression.
      Depression itself is considered to be a heterogeneous disorder. Current findings
      suggest that "cognitive" and "somatic" symptom dimensions are related to immune
      function in different ways. So far, little research has been done on the
      longitudinal aspects of inflammation in patients with major depression,
      especially with respect to different symptom dimensions of depression. Therefore,
      we investigated which aspects of depression may predict changes in tumor necrosis
      factor-alpha (TNF-alpha) and interleukin (IL)-6 over 4 weeks. METHODS: Forty-one
      patients with major depression diagnosed according to the Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and 45 healthy
      controls were enrolled. Serum measurements of TNF-alpha and IL-6 were conducted
      at baseline and 4 weeks later. Psychometric measures included the assessment of
      cognitive-affective depressive symptoms and somatic symptoms during the last 7
      days as well as somatic symptoms during the last 2 years. RESULTS: Patients with
      depression showed increased levels of TNF-alpha (P<0.05) compared to healthy
      controls. Hierarchical regression analyses indicated that neither depressive nor
      somatic symptoms predict changes in proinflammatory cytokines in the whole sample
      of depressed patients. Moderation analyses and subsequent sex-stratified
      regression analyses indicated that higher somatoform symptoms during the last 2
      years significantly predict an increase in TNF-alpha in women with major
      depression (P<0.05) but not in men. Exploratory analyses indicated that the
      stability of TNF-alpha and IL-6 (as indicated by intraclass correlation
      coefficients) over 4 weeks was high for TNF-alpha but lower for IL-6. CONCLUSION:
      The present study demonstrated that a history of somatoform symptoms may be
      important for predicting future changes in TNF-alpha in women with major
      depression.

PMID- 25061305
TI  - Sleep duration and subjective psychological well-being in adolescence: a
      longitudinal study in Switzerland and Norway.
AB  - BACKGROUND: Adolescents' sleep duration and subjective psychological well-being
      are related. However, few studies have examined the relationship between sleep
      duration and subjective psychological well-being longitudinally across
      adolescence - a time of profound biological and psychosocial change. The aim of
      this longitudinal study was to investigate whether shorter sleep duration in
      adolescents is predictive of lower subjective psychological well-being 6 months
      and 12 months later or whether lower subjective psychological well-being is
      predictive of shorter sleep duration. METHODS: Adolescents (age range, 10.02
      15.99 years; mean age, 13.05+/-1.49 years; 51.8%, female) from German-speaking
      Switzerland (n=886) and Norway (n=715) reported their sleep duration and
      subjective psychological well-being on school days using self-rating
      questionnaires at baseline (T1), 6 months (T2), and 12 months from baseline (T3).
      RESULTS: Cross-sectional and longitudinal analyses revealed that sleep duration
      decreased with age. Longer sleep duration was concurrently associated with better
      subjective psychological well-being. Crossed-lagged autoregressive longitudinal
      panel analysis showed that sleep duration prospectively predicted subjective
      psychological well-being while there was no evidence for the reverse
      relationship. CONCLUSION: Sleep duration is predictive of subjective
      psychological well-being. The findings offer further support for the importance
      of healthy sleep patterns during adolescence.

PMID- 25061306
TI  - The effects of electroconvulsive therapy on tardive dystonia or dyskinesia
      induced by psychotropic medication: a retrospective study.
AB  - BACKGROUND: Tardive dystonia and dyskinesia are potentially irreversible
      neurological syndromes. Successful electroconvulsive treatment (ECT) has been
      reported by multiple sources; however, the existing retrospective reviews and
      open prospective trials provide little information on the response rate. METHODS:
      Eighteen consecutive patients with tardive dystonia or dyskinesia received a
      standard course of ECT to treat abnormal movement. The severity of the tardive
      dystonia and dyskinesia was evaluated using the Abnormal Involuntary Movement
      Scale (AIMS) before and after the course of ECT. The patients who displayed a
      greater than 50% improvement in the AIMS score were classified as the responders.
      RESULTS: The mean AIMS score decreased from 19.1+/-4.7 to 9.6+/-4.2. There were
      seven responders among the 18 patients, which yielded a 39% response rate.
      CONCLUSION: ECT has a moderate but significant effect on tardive dystonia and
      dyskinesia.

PMID- 25061307
TI  - Quantification of functional abilities in Rett syndrome: a comparison between
      stages III and IV.
AB  - We aimed to evaluate the functional abilities of persons with Rett syndrome (RTT)
      in stages III and IV. The group consisted of 60 females who had been diagnosed
      with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of
      5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a
      standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made
      using the Pediatric Evaluation of Disability Inventory, which has 197 items in
      the areas of self-care, mobility, and social function. The results showed that in
      the area of self-care, stage III and stage IV RTT persons had a level of 24.12
      and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22
      and stage IV had 14.64 (P<0.001), while in the area of social function, stage III
      had 17.72 and stage IV had 12.14 (P=0.016). In conclusion, although persons with
      stage III RTT have better functional abilities when compared with stage IV, the
      areas of mobility, self-care, and social function are quite affected, which shows
      a great functional dependency and need for help in basic activities of daily
      life. 

PMID- 25061309
TI  - Safety and efficacy of acarbose in the treatment of diabetes in Chinese patients.
AB  - Acarbose is an alpha-glucosidase inhibitor that is commonly used to control
      postprandial blood glucose. It functions as a competitive and reversible
      inhibitor of small intestinal brush border glucosidase, blocks the degradation of
      starch and sucrose, and delays the absorption of glucose and fructose in the
      alimentary tract. The starch content of a diet might alter the hypoglycemic
      effects of acarbose because of its mechanism of action. Chinese individuals
      consume a typical Eastern diet, which is characterized by a high intake of whole
      grains, legumes, vegetables, fruits, and fish. These dietary habits allow
      acarbose to be used extensively in the People's Republic of China. Several
      Chinese-based studies have demonstrated that the use of acarbose as a monotherapy
      had similar effects on other anti-diabetes agents in decreasing glycosylated
      hemoglobin (HbA1c) and blood glucose levels, and acarbose in combination with
      other anti-diabetic drugs could further reduce blood glucose and decrease the
      mean amplitude of glycemic excursions. Importantly, acarbose is safe and well
      tolerated, with a low incidence of adverse effects. This article provides a
      comprehensive review of the safety and efficacy of acarbose for the treatment of
      diabetes in Chinese patients. 

PMID- 25061310
TI  - Severe complications after negative pressure wound therapy in burned wounds: two
      case reports.
AB  - We present two typical cases of severe complications (sepsis and hemorrhage)
      after negative pressure wound therapy (NPWT) in burned patients. Necrotic tissues
      in some deep burn wounds are difficult to judge correctly and remove thoroughly.
      An electrically burned blood vessel looks "intact" but can easily break. Necrotic
      tissue or injured blood vessels when using NPWT are dangerous, both for causing
      sepsis and hemorrhage. This is the first article that reports the severe
      complications of NPWT in burned patients. It is imperative to heed indications
      and avoid contraindications. Proper preparation of wound beds, close observation,
      and sufficient irrigation are also crucial to avoid these severe complications,
      and there is an urgent need to substitute the central vacuum system with the low
      pressure system. 

PMID- 25061308
TI  - Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection.
AB  - According to the World Health Organization, approximately 150 million people
      worldwide are chronic carriers of hepatitis C virus (HCV). HCV infection can
      evolve into cirrhosis of the liver and its complications, which are ultimately
      responsible for more than 350,000 deaths every year. Antiviral therapy, when
      successful, is able to decrease the rate of progression and increase survival.
      Two types of therapies are currently available, ie, interferon-based therapies
      and interferon-free ones. The latter have several advantages in terms of safety
      and tolerability, and could be used even in the most advanced stages of the
      disease. However, their use is restricted to some viral genotypes (genotype 2 and
      3) and they are expensive. Several molecules are in an advanced phase of
      development. This review deals with the pharmacokinetics, pharmacodynamics,
      tolerability, and safety of asunaprevir, an inhibitor of HCV nonstructural 3
      protease. Asunaprevir exerts optimal in vitro activity particularly against HCV
      genotypes 1 and 4, and its pharmacokinetic profile enables twice daily
      administration. The drawback of asunaprevir, and of all protease inhibitors, is
      its low barrier to resistance. Consequently, it is used in association with other
      drugs to prevent resistance. Specifically, when combined with daclatasvir, an
      NS5A inhibitor, asunaprevir results in a very high rate of viral eradication in
      both treatment-naive and treatment-experienced patients, with a sustained
      virological response rate of 80%-90%. Tolerability is fair; in fact, asunaprevir
      is associated with a transient increase in aminotransferase levels, which is mild
      in most cases. In conclusion, asunaprevir is a good candidate component of
      interferon-free combinations and may revolutionize the treatment of chronic HCV
      infection in the near future. 

PMID- 25061311
TI  - Anti-N-methyl-D-aspartate-receptor encephalitis: diagnosis, optimal management,
      and challenges.
AB  - OBJECTIVE: Anti-N-methyl-D-aspartate-receptor (NMDA-R) encephalitis is a new
      autoimmune disorder, often paraneoplastic in nature, presenting with complex
      neuropsychiatric symptoms. Diagnosed serologically, this disorder is often
      responsive to immunosuppressant treatment. The objective of this review is to
      educate clinicians on the challenges of diagnosis and management of this
      disorder. MATERIALS AND METHODS: A review of the relevant literature on clinical
      presentation, pathophysiology, and recommended management was conducted using a
      PubMed search. Examination of the results identified articles published between
      2007 and 2014. RESULTS: The literature highlights the importance of recognizing
      early common signs and symptoms, which include hallucinations, seizures, altered
      mental status, and movement disorders, often in the absence of fever. Although
      the presence of blood and/or cerebrospinal fluid autoantibodies confirms
      diagnosis, approximately 15% of patients have only positive cerebrospinal fluid
      titers. Antibody detection should prompt a search for an underlying teratoma or
      other underlying neoplasm and the initiation of first-line immunosuppressant
      therapy: intravenous methylprednisolone, intravenous immunoglobulin, or
      plasmapheresis, or a combination thereof. Second-line treatment with rituximab or
      cyclophosphamide should be implemented if no improvement is noted after 10 days.
      Complications can include behavioral problems (eg, aggression and insomnia),
      hypoventilation, catatonia, and autonomic instability. Those patients who can be
      managed outside an intensive care unit and whose tumors are identified and
      removed typically have better rates of remission and functional outcomes.
      CONCLUSION: There is an increasing need for clinicians of different specialties,
      including psychiatrists, neurologists, oncologists, neurooncologists,
      immunologists, and intensivists to become familiar with this disorder and its
      potential complications. Remission can be optimized with prompt detection and
      aggressive, collaborative treatment within a multidisciplinary team.

PMID- 25061312
TI  - Serum lipid profile and its association with hypertension in Bangladesh.
AB  - BACKGROUND: Hypertension and dyslipidemia are major risk factors for
      cardiovascular disease, accounting for the highest morbidity and mortality among
      the Bangladeshi population. The objective of this study was to determine the
      association between serum lipid profiles in hypertensive patients with
      normotensive control subjects in Bangladesh. METHODS: A cross-sectional study was
      carried out among 234 participants including 159 hypertensive patients and 75
      normotensive controls from January to December 2012 in the National Centre for
      Control of Rheumatic Fever and Heart Disease in Dhaka, Bangladesh. Data were
      collected on sociodemographic factors, anthropometric measurements, blood
      pressure, and lipid profile including total cholesterol (TC), triglyceride (TG),
      low density lipoprotein (LDL), and high density lipoprotein (HDL). RESULTS: The
      mean (+/- standard deviation) systolic blood pressure and diastolic blood
      pressure of the participants were 137.94+/-9.58 and 94.42+/-8.81, respectively,
      which were higher in the hypertensive patients (P<0.001). The serum levels of TC,
      TG, and LDL were higher while HDL levels were lower in hypertensive subjects
      compared to normotensives, which was statistically significant (P<0.001). Age,
      waist circumference, and body mass index showed significant association with
      hypertensive patients (P<0.001) but not with normotensives. The logistic
      regression analysis showed that hypertensive patients had 1.1 times higher TC and
      TG, 1.2 times higher LDL, and 1.1 times lower HDL than normotensives, which was
      statistically significant (P<0.05). CONCLUSION: Hypertensive patients in
      Bangladesh have a close association with dyslipidemia and need measurement of
      blood pressure and lipid profile at regular intervals to prevent cardiovascular
      disease, stroke, and other comorbidities.

PMID- 25061314
TI  - Cardiac angiosarcoma: utility of [(18)F]fluorodeoxyglucose positron emission
      tomography-computed tomography in evaluation of residue, metastases, and
      treatment response.
AB  - Cardiac angiosarcomas are a rare form of malignancy. The majority of cases arise
      from the right atrium as mural masses. These tumors have extremely aggressive
      behavior, with early clinical symptoms that vary depending on location, size, and
      extent of the tumor. Most of these patients have a very short survival time.
      Surgical therapy is considered the best choice of therapy approach in cardiac
      angiosarcoma patients with nonmetastatic disease, even though the disease is
      rarely cured. Advanced diagnostic techniques facilitate accurate, noninvasive
      assessments of cardiac sarcomas. We report a case of a 62-year-old man with
      cardiac angiosarcoma who had multiple distant metastases that were revealed by
      [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography
      imaging. 

PMID- 25061313
TI  - Effects of aliskiren- and ramipril-based treatment on central aortic blood
      pressure in elderly with systolic hypertension: a substudy of AGELESS.
AB  - BACKGROUND: Systolic hypertension is the most common form of hypertension in
      elderly patients. There is increasing evidence that measurement of central aortic
      pressure (CAP) better accounts for cardiovascular risk than brachial blood
      pressure (BP). The Aliskiren for GEriatric LowEring of SyStolic hypertension
      (AGELESS) study in elderly patients with systolic hypertension showed that
      aliskiren-based therapy provided greater reductions in peripheral BP than
      ramipril-based therapy over 12 and 36 weeks of treatment. Here, we present CAP
      results in a substudy of elderly patients from the AGELESS study. METHODS: This
      was a post hoc analysis of a 36-week, randomized, double-blind, parallel-group,
      active-controlled, optional-titration study in patients >=65 years of age with
      systolic BP >=140 mmHg. Changes in both central and peripheral BP and pulse
      pressure (PP) and changes in systolic and PP amplification ratios from baseline
      to the week 36 end point with aliskiren-based versus ramipril-based therapy were
      analyzed. RESULTS: Of the 901 patients randomized in the overall study, 154
      patients (aliskiren, n=78; ramipril, n=76) had CAP data. Numerically comparable
      reductions were seen for central aortic systolic pressure (CASP) in aliskiren
      based therapy (baseline: 143.7+/-15.0; week 36: -20.3+/-16.2) compared with
      ramipril-based therapy (baseline: 147.9+/-11.9; week 36: -20.7+/-14.6). However,
      for the change in central aortic diastolic pressure, the least squares mean
      between-treatment difference (-3.6 mmHg [95% confidence interval, -6.76, -0.43;
      P=0.0263]) was in favor of aliskiren, while the other changes were comparable
      between the two groups with a trend in favor of aliskiren for CASP as well (-2.6
      mmHg [95% confidence interval, -7.38, 2.19; P=0.2855)]. Correlation coefficients
      for change from baseline between CASP and systolic BP and between central aortic
      pulse pressure and PP (r=0.8, P<0.0001) were highly significant. CONCLUSION:
      Aliskiren-based therapy provides comparable reductions in CASP to ramipril-based
      therapy. Although the results did not reach statistical significance, these
      findings, when coupled with those of the main study, suggest that aliskiren may
      offer effective control of central BP in elderly patients with systolic
      hypertension and may be a good alternative to ramipril.

PMID- 25061316
TI  - The effects of shared situational awareness on functional and hospital outcomes
      of hospitalized older adults with heart failure.
AB  - BACKGROUND: Functional decline of hospitalized older adults is common and
      triggers health care expenditures. Physical therapy can retard the functional
      decline that occurs during hospitalization. This study aims to examine whether
      shared situational awareness (SSA) intervention may enhance the benefits of
      physical therapy for hospitalized older persons with a common diagnosis, heart
      failure. METHOD: An SSA intervention that involved daily multidisciplinary
      meetings was applied to the care of functionally declining older adults admitted
      to the medicine floor for heart failure. Covariates were matched between the
      intervention group (n=473) and control group (n=475). Both intervention and
      control groups received physical therapy for >=0.5 hours per day. The following
      three outcomes were compared between groups: 1) disability, 2) transition to
      skilled nursing facility (SNF, post-acute care setting), and 3) 30-day
      readmission rate. RESULTS: Disability was lower in the intervention group (28%)
      than in the control group (37%) (relative risk [RR] =0.74; 95% confidence
      interval [CI], 0.35-0.97; P=0.026), and transition to SNF was lower in the
      intervention group (22%) than in the control group (30%) (RR =0.77; 95% CI, 0.39
      0.98; P=0.032). The 30-day readmission rate did not significantly differ between
      the two groups. CONCLUSION: SSA intervention enhanced the benefits of physical
      therapy for functionally declining older adults. When applied to older adults
      with heart failure in the form of daily multidisciplinary meetings, SSA
      intervention improved functional outcomes and reduced transfer to SNFs after
      hospitalization.

PMID- 25061318
TI  - Modeling pegylated liposomal doxorubicin-induced hand-foot syndrome and
      intestinal mucositis in zebrafish.
AB  - Pegylated liposomal doxorubicin (PLD) has been widely used to treat cancer. The
      adverse effects of PLD noted in clinical practice, especially hand-foot syndrome
      (HFS), are regarded as unique, and the management methods for them remain
      limited. This study was aimed at developing a feasible experimental model for
      translational medicine to solve this clinical issue by using skin fluorescent
      transgenic zebrafish. We established an optimal protocol for the administration
      of Lipo-DoxTM, a PLD in current clinical use, to the Tg(k18:dsred) zebrafish line
      expressing red fluorescence in keratinocytes. We made use of bodyweight, survival
      rate, gross observation, flssuorescent microscopic assessment, and pathological
      examination of the zebrafish to assess this model. The consecutive administration
      protocol of PLD resulted in growth retardation of the zebrafish embryo and
      survival impairment, indicating establishment of a significant toxicity. We
      observed fin necrosis and keratinocyte dissociation phenotypes in the PLD-treated
      fish after consecutive administration. The skin toxicity induced by the Lipo-Dox
      injection was subsequently reversible, which might be compatible with a clinical
      course of skin recovery after discontinuation of Lipo-Dox administration.
      Furthermore, we found that the number of intestinal goblet cells, an important
      marker of intestinal inflammation, in the Lipo-Dox-injected zebrafish was
      markedly increased, accompanied by impaired mucosal integrity. The intestinal
      inflammation induced by Lipo-Dox resembled the intestinal mucositis the clinical
      patients suffered from after the administration of PLD. In conclusion, we
      established a zebrafish model for PLD-induced HFS. The intestinal mucositis
      simultaneously noted in the PLD-treated zebrafish validated the similarity of
      clinical courses after administration of PLD. This model is easily assessable,
      efficient, and worthy for use in developing a new therapeutic protocol for
      prevention or treatment of HFS as well as intestinal mucositis. Further clinical
      investigations to validate the correlation between human and zebrafish data are
      warranted. 

PMID- 25061319
TI  - A single-institution experience with bevacizumab in the treatment of metastatic
      colorectal cancer and in conjunction with liver resection.
AB  - BACKGROUND: Bevacizumab is active in the treatment of metastatic colorectal
      cancer (mCRC). However, efficacy of bevacizumab has predominantly been evaluated
      on selected patients with relatively good performance status and minor
      comorbidities. We evaluated the efficacy and safety of bevacizumab in unselected
      patients with mCRC, some of whom underwent liver resection. MATERIAL AND METHODS:
      All patients with inoperable mCRC, fit for combination chemotherapy (n=180), who
      were initially not resectable, not included into studies and without
      contraindications to bevacizumab, and initiated on bevacizumab at the Helsinki
      University Central Hospital between April 2004 and December 2005 were included
      (n=114). Most (n=70) received 5-fluorouracil/leucovorin/irinotecan plus
      bevacizumab as first-line therapy. The remainder (n=44) of the patients received
      bevacizumab in combination with oxaliplatin or irinotecan with or without 5
      fluorouracil or capecitabine. Minimum follow-up was 7 years. Treatment response
      was evaluated every 8-10 weeks according to RECIST criteria. RESULTS: Median age
      was 59.6 years (range 35-79); male/female ratio was 54%/46%; World Health
      Organization performance status 0/1/2-3 was 33%/55%/11%, respectively; and the
      number of metastatic sites, one/two/three or more, was 31%/21%/48%, respectively.
      Median duration of bevacizumab therapy was 7.8 months (range 0.5-70.5 with
      pauses). In first-line (n=40), response rate (RR) was 62%, progression-free
      survival (PFS) 11.7 months, and overall survival (OS) 22.1 months. In second-line
      (n=43), RR was 44%, PFS 8.7 months, and OS 18.7 months. In later lines (n=31), RR
      was 14%, PFS 6.7 months, and OS 14.2 months. Ten patients with initially
      unresectable liver metastases became operable and R0 resection was achieved in
      90% (9/10 resections). In 23% (7/31) of operated metastases, no vital tumor cells
      were found in histologic examination. Operative morbidity was low: two mild
      infections, no increased bleeding tendency was noticed, and no impaired wound
      healing occurred. DISCUSSION: Bevacizumab-containing combination therapy was
      effective with acceptable tolerability in an unselected mCRC patient population
      in which liver resections could be safely performed.

PMID- 25061317
TI  - Identifying and meeting the challenges of insulin therapy in type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is a chronic illness that requires clinical
      recognition and treatment of the dual pathophysiologic entities of altered
      glycemic control and insulin resistance to reduce the risk of long-term micro-
      and macrovascular complications. Although insulin is one of the most effective
      and widely used therapeutic options in the management of diabetes, it is used by
      less than one-half of patients for whom it is recommended. Clinician-, patient-,
      and health care system-related challenges present numerous obstacles to insulin
      use in T2DM. Clinicians must remain informed about new insulin products, emerging
      technologies, and treatment options that have the potential to improve adherence
      to insulin therapy while optimizing glycemic control and mitigating the risks of
      therapy. Patient-related challenges may be overcome by actively listening to the
      patient's fears and concerns regarding insulin therapy and by educating patients
      about the importance, rationale, and evolving role of insulin in individualized
      self-treatment regimens. Enlisting the services of Certified Diabetes Educators
      and office personnel can help in addressing patient-related challenges. Self
      management of diabetes requires improved patient awareness regarding the
      importance of lifestyle modifications, self-monitoring, and/or continuous glucose
      monitoring, improved methods of insulin delivery (eg, insulin pens), and the
      enhanced convenience and safety provided by insulin analogs. Health care system
      related challenges may be improved through control of the rising cost of insulin
      therapy while making it available to patients. To increase the success rate of
      treatment of T2DM, the 2012 position statement from the American Diabetes
      Association and the European Association for the Study of Diabetes focused on
      individualized patient care and provided clinicians with general treatment goals,
      implementation strategies, and tools to evaluate the quality of care. 

PMID- 25061320
TI  - Correlation between EGFR mutation status and response to first-line platinum
      based chemotherapy in patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: The purpose of this research was to investigate the relationship
      between epidermal growth factor receptor (EGFR) mutations and the response to
      first-line chemotherapy in patients with advanced non-small cell lung cancer
      (NSCLC). METHODS: A total of 266 patients with stage IIIB or IV NSCLC who
      received platinum-based doublet therapies as first-line chemotherapy were
      investigated retrospectively, and their clinical data were assessed according to
      EGFR mutation. RESULTS: EGFR mutations were identified in 45.5% of patients.
      There was no significant difference in response rate between EGFR mutation
      carriers and EGFR wild-type carriers (P=0.484). Among the patients with Kirsten
      rat sarcoma viral oncogene homolog (KRAS) wild-type, however, those with EGFR
      mutations responded better to treatment than EGFR wild-type patients (46.2%
      versus 20.8%, P=0.043). The disease control rate associated with pemetrexed-based
      treatments was higher than for vinorelbine-based therapies in EGFR mutation
      patients (P=0.001). EGFR mutation was found in patients with longer progression
      free survival and median survival time, and improved 1-year and 2-year overall
      survival when compared with EGFR wild-type patients (6.1 versus 5.0 months,
      P=0.004; 18.9 versus 13.8 months, P=0.001; 81.0% versus 63.4%, P=0.002; and 33.9%
      versus 22.8% P=0.044, respectively). Patients with the EGFR exon 19 mutation had
      longer progression-free survival than those with EGFR exon 21 mutation (P=0.007).
      Multivariate analysis showed that the response to first-line chemotherapy and the
      presence of EGFR mutations were independent prognostic factors in patients with
      advanced NSCLC. CONCLUSION: Our data showed that the presence of EGFR mutations
      meant longer survival times for patients with advanced NSCLC who received
      platinum-based doublet first-line chemotherapy, especially in those with the exon
      19 deletion mutation. Among KRAS wild-type patients, those with EGFR mutation
      responded better to first-line chemotherapy than EGFR wild-type patients.

PMID- 25061321
TI  - Expression profiles and initial confirmation of long noncoding RNAs in Chinese
      patients with pulmonary adenocarcinoma.
AB  - BACKGROUND: The purpose of this study was to investigate differentially expressed
      long noncoding RNAs (lncRNAs) in pulmonary adenocarcinoma tissue and adjacent
      noncancerous tissue from Chinese patients using lncRNA expression microarray and
      preliminary analysis. METHODS: RNA extracted from three paired pulmonary
      adenocarcinoma tissue and adjacent noncancerous tissue specimens was used to
      synthesize double-stranded complementary DNA after labeling and hybridization.
      The complementary DNA was labeled and hybridized to the lncRNA expression
      microarray, and array data were analyzed for hierarchical clustering. Gene
      coexpression networks were constructed to identify interactions among genes. To
      validate the microarray findings, we measured the relative expression levels of
      four random differentially expressed lncRNAs in the same tissue used for
      microarray using real-time quantitative polymerase chain reaction. The expression
      level of one lncRNA, AK124939, in the paired pulmonary adenocarcinoma/adjacent
      noncancerous tissue of another 30 patients was measured using real-time
      quantitative polymerase chain reaction. The experimental data were further
      analyzed and compared with clinical features. RESULTS: Of 39,000 lncRNAs
      investigated, 704 were differentially expressed in pulmonary adenocarcinoma
      tissue; 385 were upregulated and 319 were downregulated compared with those in
      the adjacent noncancerous tissue (fold change >=2 and <=-2, P<0.05). AK124939
      expression levels in poorly differentiated adenocarcinoma tissue were lower than
      those found in well to moderately differentiated adenocarcinoma tissue (P=0.05).
      CONCLUSION: There are significant differences in the lncRNA expression profiles
      in Chinese patients with pulmonary adenocarcinoma. LncRNAs such as AK124939 may
      be anticancer factors related to the progression of pulmonary adenocarcinoma.

PMID- 25061322
TI  - Histological type-specific prognostic factors of cervical small cell
      neuroendocrine carcinoma, adenocarcinoma, and squamous cell carcinoma.
AB  - BACKGROUND: The study aimed to determine the prognostic impact of clinical and
      pathological factors on survival among patients with small cell neuroendocrine
      carcinoma (SNEC), adenocarcinoma (ADC), and squamous cell carcinoma (SCC).
      METHODS: Eligible participants were all patients with histologically confirmed
      cervical cancer treated at Chiang Mai University Hospital between 1995 and 2011.
      We included all patients with SNEC and randomly enrolled patients with ADC and
      SCC. We used competing-risk regression analysis to examine the risk of cancer
      related death by histological type. RESULTS: We included 130 (6.2%) women with
      SNEC, 346 (16.4%) with ADC, and 1,632 (77.4%) with SCC. Age >60 years (hazard
      ratio [HR] 4.9, 95% confidence interval [CI] 2.0-12.0) and lymph node involvement
      (HR 3.0, 95% CI 1.2-7.4) were prognostic factors among surgically-treated
      patients with SNEC. Deeper stromal invasion (HR 3.6, 95% CI 1.6-8.3) was a
      prognostic factor in patients with SCC. In patients with advanced SNEC, age >60
      years had a strong prognostic impact (HR 2.6, 95% CI 1.0-6.5) while the
      International Federation of Gynecology and Obstetrics stages III and IV were
      prognostic factors for patients with advanced stage ADC (HR 2.9, 95% CI 2.0-4.4
      and HR 4.5, 95% CI 2.6-7.9, respectively) and SCC (HR 1.7, 95% CI 1.4-2.0 and HR
      3.7, 95% CI 2.8-4.9, respectively) compared with the International Federation of
      Gynecology and Obstetrics stage IIB. CONCLUSION: Clinical and pathological
      prognostic factors in cervical cancer differed according to histological type.
      Taking the important prognostic factors for each histological type into
      consideration may be beneficial for tailored treatment and follow-up planning.

PMID- 25061323
TI  - Safety and feasibility of antibiotic de-escalation in bacteremic pneumonia.
AB  - BACKGROUND: Antibiotic de-escalation is a potential strategy advocated to
      conserve the effectiveness of broad-spectrum antibiotics. The aim of this study
      was to examine the safety and feasibility of antibiotic de-escalation in patients
      admitted with bacteremic pneumonia. METHODS: A retrospective chart review was
      done for patients with bacteremic pneumonia admitted to Northwest Texas Hospital
      in Amarillo, TX, USA, during 2008. Antibiotic de-escalation was defined as
      changing the empiric antibiotic regimen to a culture-directed single agent with a
      narrower spectrum than the original regimen. RESULTS: Sixty-eight patients were
      admitted with bacteremic pneumonia. Eight patients were not eligible for de
      escalation. Among the 60 patients who were eligible for de-escalation, the
      treating physicians failed to de-escalate antibiotics in 27 cases (45.0%).
      Discharge to a long-term care facility predicted failure to de-escalate
      antibiotics, while an infectious diseases consultation was significantly
      associated with antibiotic de-escalation. The average daily cost of antibacterial
      therapy in the de-escalation group was $25.7 compared with $61.6 in the group
      where de-escalation was not implemented. The difference in mean length of
      hospital stay and mortality between the two groups was not statistically
      significant. CONCLUSION: Antibiotic de-escalation is a safe management strategy
      but unfortunately is not widely adopted. Although bacterial resistance poses a
      significant threat and is rising, antimicrobial de-escalation has emerged as a
      potential intervention that can conserve the effectiveness of broad-spectrum
      antibiotics without compromising the patient's outcome. This practice is becoming
      important in the face of slow development of new anti-infective agents.

PMID- 25061324
TI  - Management of adult diabetic ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is a rare yet potentially fatal hyperglycemic crisis
      that can occur in patients with both type 1 and 2 diabetes mellitus. Due to its
      increasing incidence and economic impact related to the treatment and associated
      morbidity, effective management and prevention is key. Elements of management
      include making the appropriate diagnosis using current laboratory tools and
      clinical criteria and coordinating fluid resuscitation, insulin therapy, and
      electrolyte replacement through feedback obtained from timely patient monitoring
      and knowledge of resolution criteria. In addition, awareness of special
      populations such as patients with renal disease presenting with DKA is important.
      During the DKA therapy, complications may arise and appropriate strategies to
      prevent these complications are required. DKA prevention strategies including
      patient and provider education are important. This review aims to provide a brief
      overview of DKA from its pathophysiology to clinical presentation with in depth
      focus on up-to-date therapeutic management. 

PMID- 25061325
TI  - Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with
      orlistat or sibutramine further improves the body-weight reduction and glucose
      homeostasis of obese rats fed a cafeteria diet.
AB  - The present study assessed the potential of the sodium glucose-linked transporter
      (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone
      or in combination with the clinically effective weight-loss agents orlistat and
      sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed
      to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10,
      30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed
      using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or
      orlistat. Body weight, food, and water intake were recorded daily. The effect of
      drug treatment on glucose tolerance, relevant plasma parameters, and carcass
      composition was determined. Empagliflozin dose-dependently reduced body weight,
      plasma leptin, and body fat though increased urinary glucose excretion. The
      combination of empagliflozin and orlistat significantly reduced body weight
      compared to animals treated with either drug alone, and significantly improved
      glucose tolerance, plasma insulin, and leptin compared to vehicle-treated
      controls. The effect of sibutramine to improve glycemic control in an oral
      glucose-tolerance test was also significantly increased, with empagliflozin and
      combination treatment leading to a reduction in carcass fat greater than that
      observed with either drug alone. These data demonstrate that empagliflozin
      reduces body weight in cafeteria-fed obese rats. In combination studies,
      empagliflozin further improved the body-weight or body-fat loss of animals in
      comparison to orlistat or sibutramine alone. Such studies may indicate improved
      strategies for the treatment of obese patients with prediabetes or type 2
      diabetes. 

PMID- 25061326
TI  - Cryolipolysis for noninvasive body contouring: clinical efficacy and patient
      satisfaction.
AB  - In recent years, a number of modalities have become available for the noninvasive
      reduction of adipose tissue, including cryolipolysis, radiofrequency, low-level
      laser, and high-intensity focused ultrasound. Each technology employs a different
      mechanism of action to cause apoptosis or necrosis of the targeted adipocytes.
      Among these technologies, cryolipolysis has not only been commercially available
      for the longest time, but has also been best researched including in vitro and
      animal models and randomized controlled clinical trials in humans. The principle
      behind cryolipolysis exploits the premise that adipocytes are more susceptible to
      cooling than other skin cells. The precise application of cold temperatures
      triggers apoptosis of the adipocytes, which invokes an inflammatory response and
      leads to slow digestion by surrounding macrophages. In clinical studies,
      cryolipolysis was shown to reduce subcutaneous fat at the treatment site by up to
      25% after one treatment. Improvements were seen in 86% of treated subjects. At
      73%, the patient satisfaction rate is higher than with other technologies used
      for noninvasive lipolysis. Cryolipolysis has been proven to be a very safe method
      for body contouring, and is accomplished with only minimal discomfort. Expected
      side effects are temporary erythema, bruising, and transient numbness that
      usually resolve within 14 days after treatment. With a prevalence of 0.1%, the
      most common complaint is late-onset pain, occurring 2 weeks post-procedure, which
      resolves without intervention. Although no procedure has been accepted as the
      gold standard for noninvasive body contouring as yet, cryolipolysis is considered
      to be both safe and efficient with a high patient satisfaction rate. 

PMID- 25061327
TI  - Genetic polymorphisms and skin aging: the identification of population genotypic
      groups holds potential for personalized treatments.
AB  - INTRODUCTION: Skin changes are among the most visible signs of aging. Skin
      properties such as hydration, elasticity, and antioxidant capacity play a key
      role in the skin aging process. Skin aging is a complex process influenced by
      heritable and environmental factors. Recent studies on twins have revealed that
      up to 60% of the skin aging variation between individuals can be attributed to
      genetic factors, while the remaining 40% is due to non-genetic factors. Recent
      advances in genomics and bioinformatics approaches have led to the association of
      certain single nucleotide polymorphisms (SNPs) to skin properties. Our aim was to
      classify individuals based on an ensemble of multiple polymorphisms associated
      with certain properties of the skin for providing personalized skin care and anti
      aging therapies. METHODS AND RESULTS: We identified the key proteins and SNPs
      associated with certain properties of the skin that contribute to skin aging. We
      selected a set of 13 SNPs in gene coding for these proteins which are potentially
      associated with skin aging. Finally, we classified a sample of 120 female
      volunteers into ten clusters exhibiting different skin properties according to
      their genotypic signature. CONCLUSION: This is the first study that describes the
      actual frequency of genetic polymorphisms and their distribution in clusters
      involved in skin aging in a Caucasian population. Individuals can be divided into
      genetic clusters defined by genotypic variables. These genotypic variables are
      linked with polymorphisms in one or more genes associated with certain properties
      of the skin that contribute to a person's perceived age. Therefore, by using this
      classification, it is possible to characterize human skin care and anti-aging
      needs on the basis of an individual's genetic signature, thus opening the door to
      personalized treatments addressed at specific populations. This is part of an
      ongoing effort towards personalized anti-aging therapies combining genetic
      signatures with environmental and life style evaluations.

PMID- 25061329
TI  - Potentiated clinoptilolite: artificially enhanced aluminosilicate reduces
      symptoms associated with endoscopically negative gastroesophageal reflux disease
      and nonsteroidal anti-inflammatory drug induced gastritis.
AB  - PURPOSE: The cation exchanger, a potentiated clinoptilolite (AbsorbatoxTM 2.4D),
      is a synthetically enhanced aluminosilicate. The aim of this study was to
      evaluate the possible benefits of a potentiated clinoptilolite as a
      gastroprotective agent in reducing the severity of clinical symptoms and signs
      associated with 1) endoscopically negative gastroesophageal reflux disease
      (ENGORD) and 2) nonsteroidal anti-inflammatory drug (NSAID) medication. METHODS
      AND PATIENTS: Two randomized, double-blind, placebo-controlled, pilot studies,
      the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy,
      a total of 25 patients suffering from ENGORD were randomized to receive either
      placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study
      recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or
      placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent
      gastroscopic evaluation of their stomach linings prior to and on day 14 of the
      study. Gastric biopsies were obtained and evaluated via the upgraded Sydney
      system, whereas visible gastric events and status of the gastric mucosa were
      evaluated via a 0-3 rating scale. During both studies, patients recorded gastric
      symptoms in a daily symptom diary. RESULTS: In the ENGORD study, patients who
      received the potentiated clinoptilolite reported a significant reduction
      (P<=0.05) in severity of symptoms including reduction in heartburn (44%),
      discomfort (54%), and pain (56%). Symptom-free days improved by 41% compared to
      the group who received placebo (not significant). This was over and above the
      benefits seen with the proton pump inhibitor. In the NSAID study, the reduction
      in gastric symptom severity was echoed in the group who received the potentiated
      clinoptilolite. Treatment with the potentiated clinoptilolite resulted in
      significant prevention (P<=0.05) of mucosal erosion severity as graded by the
      gastroenterologist. CONCLUSION: Absorbatox is a nonabsorbable aluminosilicate
      with potential gastroprotective benefits as it protected against ENGORD symptoms
      and NSAID-induced gastric events. The exact mechanism of action is not clear but
      may be due to its binding to hydrogen ions and biologically active amines and
      nitrates.

PMID- 25061328
TI  - S1pping fire: Sphingosine-1-phosphate signaling as an emerging target in
      inflammatory bowel disease and colitis-associated cancer.
AB  - Inflammatory bowel disease (IBD) is a complex disease that involves unpredictable
      and destructive inflammation in the gastrointestinal tract resulting in
      gastrointestinal symptoms, infection, and tissue destruction, and which can be
      associated with an increased risk of colon cancer. The underlying cause of IBD
      involves disruption of the innate and adaptive immune mechanisms that maintain
      homeostasis between the gut mucosa and its environment. Elucidating how the
      homeostatic mechanisms controlling gut mucosal immunity and inflammation are
      disrupted in IBD represents the first steps to identifying novel therapeutic
      targets. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that is
      enriched in the blood and lymph, and functions in innate and adaptive immunity.
      S1P signaling regulates inflammation via its impact on the trafficking,
      differentiation, and effector functions of bone marrow-derived immune cells. S1P
      also activates nuclear factor kappa B and signal transducer and activator of
      transcription 3 inflammatory pathways. S1P is generated by the ubiquitously
      expressed lipid kinase, sphingosine kinase (SphK)1 and its tissue-restricted
      homolog, SphK2. S1P is irreversibly degraded by S1P lyase, which is highly
      expressed in enterocytes. Recent studies targeting S1P metabolism and signaling
      have shown promise in preclinical models of IBD and have shed light on the
      mechanisms by which S1P signaling impacts IBD. The evidence suggests that
      targeting S1P signaling and metabolism may represent a novel strategy in treating
      IBD and it may reduce colon cancer risk by interrupting the progression from
      inflammation to carcinogenesis. 

PMID- 25061330
TI  - An epidemiologic model to project the impact of changes in glomerular filtration
      rate on quality of life and survival among persons with chronic kidney disease.
AB  - PURPOSE: Predicting the timing and number of end-stage renal disease (ESRD) cases
      from a population of individuals with pre-ESRD chronic kidney disease (CKD) has
      not previously been reported. The objective is to predict the timing and number
      of cases of ESRD occurring over the lifetime of a cohort of hypothetical CKD
      patients in the US based on a range of baseline estimated glomerular filtration
      rate (eGFR) values and varying rates of eGFR decline. METHODS: A three-state
      Markov model - functioning kidney, ESRD, and death - with an annual cycle length
      is used to project changes in baseline eGFR on long-term health outcomes in a
      hypothetical cohort of CKD patients. Using published eGFR-specific risk equations
      and adjusting for predictive characteristics, the probability of ESRD (eGFR <10),
      time to death, and incremental cost-effectiveness ratios for hypothetical
      treatments (costing US$10, $5, and $2/day), are projected over the cohort's
      lifetime under two scenarios: an acute drop in eGFR (mimicking acute kidney
      injury) and a reduced hazard ratio for ESRD (mimicking an effective
      intervention). RESULTS: Among CKD patients aged 50 years, an acute eGFR decrement
      from 45 mL/minute to 35 mL/minute yields decreases of 1.6 life-years, 1.5 quality
      adjusted life-years (QALYs), 0.8 years until ESRD, and an increase of 183 per
      1,000 progressing to ESRD. Among CKD patients aged 60 years, lowering the hazard
      ratio of ESRD to 0.8 yields values of 0.2, 0.2, 0.2, and 46 per 1,000,
      respectively. Incremental cost-effectiveness ratios are higher (ie, less
      favorable) for higher baseline eGFR, indicating that interventions occurring
      later in the course of disease are more likely to be economically attractive.
      CONCLUSION: Both acute kidney injury and slowing the rate of eGFR decline produce
      substantial shifts in expected numbers and timing of ESRD among CKD patients.
      This model is a useful tool for planning management of CKD patients.

PMID- 25061331
TI  - Cardiac arrest teams and time of day: effects on surviving in-hospital
      resuscitation.
AB  - OBJECTIVES: Little is known about the factors that influence survival following
      in-hospital resuscitation, but previous investigations have suggested that in
      hospital resuscitations outside of regular working hours are associated with
      worse survival rates. MATERIAL AND METHODS: In-hospital cardiac arrest teams at
      our hospital were instructed to complete a questionnaire following every
      emergency call between July 2011 and June 2013. Data on all resuscitation
      attempts were collected and analyzed. RESULTS: A total of 65 in-hospital
      resuscitations were recorded in 42 males (64.6%) and 23 females (35.4%) (mean age
      72.0+/-14.3 years). A total of 54 (83.1%) cardiac arrests were witnessed; seven
      (10.8%) showed a shockable rhythm at the time of the first ECG. Resuscitation
      attempts lasted 29.3+/-41.3 minutes, and 4.1+/-3.1 mg epinephrine was given.
      Return of spontaneous circulation could be achieved in 38 patients (58.5%); 29
      (44.6%) survived the first day, 23 (35.4%) the seventh day, and 15 patients
      (23.1%) were discharged alive. Significantly more in-hospital resuscitations were
      obtained for those performed during non-regular working hours (P<0.001), with
      higher neuron-specific enolase levels at 72 hours after resuscitation during
      nonregular working hours (P=0.04). Patients who were discharged alive were
      significantly younger (P=0.01), presented more often with an initial shockable
      rhythm (P=0.04), and had a shorter duration of resuscitation (P<0.001) with the
      need of a lower dose of epinephrine (P<0.001). DISCUSSION: Survival rates
      following in-hospital resuscitation were poor at any time, but appear to depend
      less on time-dependent effects of the quality of resuscitation and more on time
      dependent effects of recognition of cardiac arrests.

PMID- 25061332
TI  - Kearns-Sayre syndrome: a case series of 35 adults and children.
AB  - BACKGROUND: Kearns-Sayre syndrome (KSS) is a rare mitochondrial cytopathy, first
      described at Mayo Clinic in 1958. AIMS: We aimed to define patient and disease
      characteristics in a large group of adult and pediatric patients with KSS.
      METHODS: We retrospectively searched the Mayo Clinic medical index patient
      database for the records of patients with KSS between 1976 and 2009. The 35
      patients identified with KSS were analyzed in terms of demographic
      characteristics, presenting signs and symptoms, diagnostic features, clinical
      evolution, and associations between disease features and the development of
      disability. RESULTS: The mean (standard [SD]) age at KSS presentation was 17 (10)
      years, but the mean age at diagnosis was 26 (15) years. Ophthalmologic symptoms
      developed in all patients, and neurologic and cardiac involvement was common.
      Only four patients (11%) in the series died, but all deaths were from sudden
      cardiac events. The development of physical disability was significantly
      associated with cognitive decline (P=0.004) but not with other clinical features,
      such as sex or sudden cardiac death. CONCLUSION: We report the largest case
      series to date of patients with KSS from a single institution. In addition to the
      conduction system abnormalities identified in previous series, our cohort
      included patients with syncope and sudden cardiac death. This underscores the
      need to consider formal electrophysiologic studies and prophylactic
      defibrillators in patients with KSS.

PMID- 25061333
TI  - Lung cancer trends: smoking, obesity, and sex assessed in the Staten Island
      University's lung cancer patients.
AB  - INTRODUCTION: The incidence of lung cancer in the United States decreased by 1.8%
      from 1991 to 2005 while it increased by 0.5% in females. We assessed whether
      nonsmokers afflicted with lung cancer at Staten Island University Hospital are
      disproportionately female in comparison to national averages. We also evaluated
      different factors including race, histology, and body mass index (BMI) in
      correlation with smoking history. METHODS: A retrospective chart review was
      conducted from 2005 to 2011 on 857 patients. Patients were divided into two
      groups according to their smoking status: current or ever-smokers, and former or
      never-smokers. A chi-square test for categorical data and multivariate logistic
      regression analyses was used to study the relation between BMI and the other
      clinical and demographic data. RESULTS: Forty-nine percent of patients were men
      and 51% were women with a mean age at diagnosis of 67.8 years. Current smokers
      were most common (50.2%) followed by ever-smokers (18.2%), former smokers (15.8%)
      and never-smokers (15.6%). Forty eight percent had stage IV lung cancer upon
      presentation. Never-smokers with lung cancer were 24 times more likely to be
      females. However, the proportion of female former smokers (31.6%) was lower than
      the proportion of male former smokers (68.4%) (P=0.001). There was no significant
      association between American Joint Committee on Cancer (AJCC) stage, sex, race,
      and histological type in the two smoking groups. Current/ever-smokers tended to
      be younger at age of diagnosis (P=0.0003). BMI was lower in the current/ever
      smokers (26.8 kg/m(2)) versus former/never-smokers (28.8) in males (P=0.0005).
      BMI was significantly higher in males (30.26) versus females (25.25) in the never
      smoker category (P=0.004). Current smokers, compared to others, had a lower BMI
      in males (26.4 versus 28.3; P=0.0001) and females (25.5 versus 26.9; P=0.013) but
      the mean BMI for all groups was in the overweight/obese range. CONCLUSION: Our
      population of lung cancer patients although demographically distinct, reflects a
      similar proportion of afflicted nonsmokers to the national population. Smoking is
      a major risk factor for lung cancer, but there is also a possible direct
      correlation with BMI that would support obesity as a potential risk factor for
      lung cancer.

PMID- 25061334
TI  - Efficacy and tolerability of carbamazepine for the treatment of painful diabetic
      neuropathy in adults: a 12-week, open-label, multicenter study.
AB  - OBJECTIVE: Anticonvulsants are increasingly being used in the symptomatic
      management of several neuropathic pain disorders. The present observational study
      was designed to evaluate the efficacy, tolerability, and quality of life (QoL) of
      carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in
      Pakistan. METHODS: This was a 12-week, multicenter, open-label, uncontrolled
      trial in adult type 2 diabetic patients (aged 18-65 years) suffering from
      clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score
      >=4). Change in neuropathic pain at week 12 compared with baseline was assessed
      using the Brief Pain Inventory Scale-Short Form (pain severity score and pain
      interference score). QoL was determined by the American Chronic Pain Association
      QoL scale. Safety was assessed based on patient reported adverse events (AEs) and
      serious AEs. RESULTS: Of the total 500 screened patients, 452 enrolled and
      completed the study. The mean (+/- standard deviation [SD]) pain interference
      score decreased from 4.5+/-2.0 at baseline to 3.1+/-1.9 at week 12 (P<0.001). The
      mean (+/- SD) pain severity score decreased from 5.8+/-2.0 at baseline to 3.6+/
      2.2 at week 12 (P<0.001). There was a decrease of >=30% in the pain severity
      score between visits. The mean (+/- SD) QoL scale score improved from 5.9+/-1.6
      at baseline to 8.0+/-1.7 at week 12. A total of ten (2.2%) patients reported AEs
      during the study period. No patient discontinued the study due to AEs.
      CONCLUSION: In this real-life experience study, carbamazepine, when prescribed
      for 12 weeks to adult diabetic patients suffering from neuropathic pain, showed
      pain-relief effect, with reduced mean pain severity and mean pain interference
      scores and with improved QoL and good tolerability profile.

PMID- 25061335
TI  - Patient-related barriers to hypertension control in a Nigerian population.
AB  - BACKGROUND: Hypertension control is a challenge globally. Barriers to optimal
      control exist at the patient, physician, and health system levels. Patient
      related barriers in our environment are not clear. The aim of this study was to
      identify patient-related barriers to control of hypertension among adults with
      hypertension in a semiurban community in South-East Nigeria. METHODS: This was a
      cross-sectional descriptive study of patients with a diagnosis of hypertension
      and on antihypertensive medication. RESULTS: A total of 252 participants were
      included in the survey, and comprised 143 males (56.7%) and 109 females (43.3%).
      The mean age of the participants was 56.6+/-12.7 years, with a diagnosis of
      hypertension for a mean duration of 6.1+/-3.3 years. Among these patients, 32.9%
      had controlled blood pressure, while 39.3% and 27.8%, respectively, had stage 1
      and stage 2 hypertension according to the Seventh Report of the Joint National
      Committee on Prevention, Detection and Evaluation of High Blood Pressure. Only
      23.4% knew the consequences of poor blood pressure control and 64% were expecting
      a cure from treatment even when the cause of hypertension was not known.
      Furthermore, 68.7% showed low adherence to medication, the reported reasons for
      which included forgetfulness (61.2%), financial constraints (56.6%), high pill
      burden (22.5%), side effects of medication (17.3%), and low measured blood
      pressure (12.1%). Finally, knowledge and practice of the lifestyle modifications
      necessary for blood pressure control was inadequate among the participants.
      CONCLUSION: Poor knowledge regarding hypertension, unrealistic expectations of
      treatment, poor adherence with medication, unawareness of lifestyle modification,
      and failure to apply these were identified as patient-related barriers to blood
      pressure control in this study.

PMID- 25061337
TI  - Health care utilization and expenditures among Medicaid beneficiaries with
      neuropathic pain following spinal cord injury.
AB  - BACKGROUND: The study aimed to evaluate health care resource utilization (HRU)
      and costs for neuropathic pain (NeP) secondary to spinal cord injury (SCI) among
      Medicaid beneficiaries. METHODS: The retrospective longitudinal cohort study used
      Medicaid beneficiary claims with SCI and evidence of NeP (SCI-NeP cohort) matched
      with a cohort without NeP (SCI-only cohort). Patients had continuous Medicaid
      eligibility 6 months pre- and 12 months postindex, defined by either a diagnosis
      of central NeP (ICD-9-CM code 338.0x) or a pharmacy claim for an NeP-related
      antiepileptic or antidepressant drug within 12 months following first SCI
      diagnosis. Demographics, clinical characteristics, HRU, and expenditures were
      compared between cohorts. RESULTS: Propensity score-matched cohorts each
      consisted of 546 patients. Postindex percentages of patients with physician
      office visits, emergency department visits, SCI- and pain-related procedures, and
      outpatient prescription utilization were all significantly higher for SCI-NeP
      (P<0.001). Using regression models to account for covariates, adjusted mean
      expenditures were US$47,518 for SCI-NeP and US$30,150 for SCI only, yielding
      incremental costs of US$17,369 (95% confidence interval US$9,753 to US$26,555)
      for SCI-NeP. Factors significantly associated with increased cost included SCI
      type, trauma-related SCI, and comorbidity burden. CONCLUSION: Significantly
      higher HRU and total costs were incurred by Medicaid patients with NeP secondary
      to SCI compared with matched SCI-only patients.

PMID- 25061336
TI  - Medication-overuse headache: a review.
AB  - Medication-overuse headache (MOH) is a worldwide health problem with a prevalence
      of 1%-2%. It is a severe form of headache where the patients often have a long
      history of headache and of unsuccessful treatments. MOH is characterized by
      chronic headache and overuse of different headache medications. Through the
      years, withdrawal of the overused medication has been recognized as the treatment
      of choice. However, currently, there is no clear consensus regarding the optimal
      strategy for management of MOH. Treatment approaches are based on expert opinion
      rather than scientific evidence. This review focuses on aspects of epidemiology,
      diagnosis, pathogenesis, prevention, and treatment of MOH. We suggest that
      information and education about the risk of MOH is important since the condition
      is preventable. Most patients experience reduction of headache days and intensity
      after successful treatment. The first step in the treatment of MOH should be
      carried out in primary care and focus primarily on withdrawal, leaving
      prophylactic medication to those who do not manage primary detoxification. For
      most patients, a general practitioner can perform the follow-up after
      detoxification. More complicated cases should be referred to neurologists and
      headache clinics. Patients suffering with MOH have much to gain by an earlier
      treatment-focused approach, since the condition is both preventable and
      treatable. 

PMID- 25061339
TI  - Joint medicine-information and pharmacovigilance services could improve detection
      and communication about drug-safety problems.
AB  - BACKGROUND: RELIS is a Norwegian network of four regional medicine-information
      and pharmacovigilance centers where pharmacists and clinical pharmacologists
      provide feedback to health care professionals in spontaneous drug-related
      questions and adverse drug-reaction (ADR) reports published in a question-answer
      pair (QAP) database (the RELIS database) and the Norwegian ADR database,
      respectively. OBJECTIVE: To describe the potential of RELIS's dual service to
      improve detection and communication of drug-safety problems. MATERIALS AND
      METHODS: We searched the RELIS database for QAPs about ADRs with use of the
      Norwegian ADR database as a reference. We also searched the Norwegian ADR
      database for reports that used the RELIS database as a reference. Both searches
      were limited to the years 2003-2012. We then selected the example of pregabalin
      and drug abuse after the marketing of Lyrica in Norway in September 2004 to
      illustrate RELIS's potential to detect new drug-safety information through a
      limited number of QAPs and ADR reports. RESULTS: A total of 5,427 (26%) of 21,071
      QAPs in the RELIS database concerned ADRs. QAPs from this database were used as
      references in 791 (4%) of a total of 22,090 reports in the Norwegian ADR
      database. The Norwegian ADR database was used as a reference in 363 (7%) of 5,427
      QAPs that concerned ADRs. Between September 2004 and September 2008, RELIS
      received eleven questions and 13 ADR reports about suspicion of Lyrica
      (pregabalin) and different aspects of abuse. CONCLUSION: RELIS processes data
      through two databases that facilitate communication about ADRs. Our service also
      has the potential to detect new drug-safety problems with a limited number of
      questions and ADR reports.

PMID- 25061338
TI  - Prognostic stratification of colorectal cancer patients: current perspectives.
AB  - Tumor staging according to the American Joint Committee on Cancer/Union for
      International Cancer Control tumor, node, metastasis (TNM) system is currently
      regarded as the standard for staging of patients with colorectal cancer. This
      system provides the strongest prognostic information for patients with early
      stage disease and those with advanced disease. For patients with intermediate
      levels of disease, it is less able to predict disease outcome. Therefore,
      additional prognostic markers are needed to improve the management of affected
      patients. Ideal markers are readily assessable on hematoxylin and eosin-stained
      tumor slides, and in this way are easily applicable worldwide. This review
      summarizes the histological features of colorectal cancer that can be used for
      prognostic stratification. Specifically, we refer to the different histological
      variants of colorectal cancer that have been identified, each of these variants
      carrying distinct prognostic significance. Established markers of adverse
      outcomes are lymphatic and venous invasion, as well as perineural invasion, but
      underreporting still occurs in the routine setting. Tumor budding and tumor
      necrosis are recent advances that may help to identify patients at high risk for
      recurrence. The prognostic significance of the antitumor inflammatory response
      has been known for quite a long time, but a lack of standardization prevented its
      application in routine pathology. However, scales to assess intra- and
      peritumoral inflammation have recently emerged, and can be expected to strengthen
      the prognostic significance of the pathology report. 

PMID- 25061340
TI  - The influence of psychoeducation on regulating biological rhythm in a sample of
      patients with bipolar II disorder: a randomized clinical trial.
AB  - INTRODUCTION: Changes in biological rhythm are among the various characteristics
      of bipolar disorder, and have long been associated with the functional impairment
      of the disease. There are only a few viable options of psychosocial interventions
      that deal with this specific topic; one of them is psychoeducation, a model that,
      although it has been used by practitioners for some time, only recently have
      studies shown its efficacy in clinical practice. AIM: To assess if patients
      undergoing psychosocial intervention in addition to a pharmacological treatment
      have better regulation of their biological rhythm than those only using
      medication. METHOD: This study is a randomized clinical trial that compares a
      standard medication intervention to an intervention combined with drugs and
      psychoeducation. The evaluation of the biological rhythm was made using the
      Biological Rhythm Interview of Assessment in Neuropsychiatry, an 18-item scale
      divided in four areas (sleep, activity, social rhythm, and eating pattern). The
      combined intervention consisted of medication and a short-term psychoeducation
      model summarized in a protocol of six individual sessions of 1 hour each.
      RESULTS: The sample consisted of 61 patients with bipolar II disorder, but during
      the study, there were 14 losses to follow-up. Therefore, the final sample
      consisted of 45 individuals (26 for standard intervention and 19 for combined).
      The results showed that, in this sample and time period evaluated, the combined
      treatment of medication and psychoeducation had no statistically significant
      impact on the regulation of biological rhythm when compared to standard
      pharmacological treatment. CONCLUSION: Although the changes in biological rhythm
      were not statistically significant during the time period evaluated in this
      study, it is noteworthy that the trajectory of the score showed a trend towards
      improvement, which may indicate a positive impact on treatment, though it may
      take a longer time than expected.

PMID- 25061341
TI  - Impacts of pay for performance on the quality of primary care.
AB  - Increasingly, financial incentives are being used in health care as a result of
      increasing demand for health care coupled with fiscal pressures. Financial
      incentive schemes are one approach by which the system may incentivize providers
      of health care to improve productivity and/or adapt to better quality provision.
      Pay for performance (P4P) is an example of a financial incentive which seeks to
      link providers' payments to some measure of performance. This paper provides a
      discussion of the theoretical underpinnings of P4P, gives an overview of the
      health P4P evidence base, and provide a detailed case study of a particularly
      large scheme from the English National Health Service. Lessons are then drawn
      from the evidence base. Overall, we find that the evidence for the effectiveness
      of P4P for improving quality of care in primary care is mixed. This is to some
      extent due to the fact that the P4P schemes used in primary care are also mixed.
      There are many different schemes that incentivize different aspects of care in
      different ways and in different settings, making evaluation problematic. The
      Quality and Outcomes Framework in the United Kingdom is the largest example of
      P4P in primary care. Evidence suggests incentivized quality initially improved
      following the introduction of the Quality and Outcomes Framework, but this was
      short-lived. If P4P in primary care is to have a long-term future, the question
      about scheme effectiveness (perhaps incorporating the identification and
      assessment of potential risk factors) needs to be answered robustly. This would
      require that new schemes be designed from the onset to support their evaluation:
      control and treatment groups, coupled with before and after data. 

PMID- 25061343
TI  - First record of the mygalomorph spider family Paratropididae (Arachnida, Araneae)
      in North America with the description of a new species of Paratropis Simon from
      Mexico, and with new ultramorphological data for the family.
AB  - A new species of the genus Paratropis is described from North America: Paratropis
      tuxtlensis sp. n., from a tropical rainforest in Veracruz, Mexico. This is the
      fifth Paratropis and the tenth paratropidid species described and the first North
      American record of this Neotropical family. The species is described based on
      adult males and females, and juveniles. The juveniles show ontogenetic variation
      in the number of cuspules on the labium and endites, and in the number and
      position of leg trichobothria. This is the second Paratropis species, and the
      third paratropidid known from both sexes. The scanning electron photographs (SEM)
      reveal new morphological data and contribute to the knowledge of the family. 

PMID- 25061344
TI  - A new species of Tullbergia (Collembola, Tullbergiidae) from Buenos Aires,
      Argentina.
AB  - A new species of Tullbergia from Argentina is described and illustrated; it is
      differentiated from Tullbergia paranensis by the number of vesicles of
      postantennal organ, pseudocelli shape and its formulae and the number of dorsal
      sensilla on Ant. IV. In addition a key for the identification of the members of
      the family from Argentina is included. 

PMID- 25061342
TI  - Nonadherence with antipsychotic medication in schizophrenia: challenges and
      management strategies.
AB  - Nonadherence with medication occurs in all chronic medical disorders. It is a
      particular challenge in schizophrenia due to the illness's association with
      social isolation, stigma, and comorbid substance misuse, plus the effect of
      symptom domains on adherence, including positive and negative symptoms, lack of
      insight, depression, and cognitive impairment. Nonadherence lies on a spectrum,
      is often covert, and is underestimated by clinicians, but affects more than one
      third of patients with schizophrenia per annum. It increases the risk of relapse,
      rehospitalization, and self-harm, increases inpatient costs, and lowers quality
      of life. It results from multiple patient, clinician, illness, medication, and
      service factors, but a useful distinction is between intentional and
      unintentional nonadherence. There is no gold standard approach to the measurement
      of adherence as all methods have pros and cons. Interventions to improve
      adherence include psychoeducation and other psychosocial interventions,
      antipsychotic long-acting injections, electronic reminders, service-based
      interventions, and financial incentives. These overlap, all have some evidence of
      effectiveness, and the intervention adopted should be tailored to the individual.
      Psychosocial interventions that utilize combined approaches seem more effective
      than unidimensional approaches. There is increasing interest in electronic
      reminders and monitoring systems to enhance adherence, eg, Short Message Service
      text messaging and real-time medication monitoring linked to smart pill
      containers or an electronic ingestible event marker. Financial incentives to
      enhance antipsychotic adherence raise ethical issues, and their place in practice
      remains unclear. Simple pragmatic strategies to improve medication adherence
      include shared decision-making, regular assessment of adherence, simplification
      of the medication regimen, ensuring that treatment is effective and that side
      effects are managed, and promoting a positive therapeutic alliance and good
      communication between the clinician and patient. These elements remain essential
      for all patients, not least for the small minority where vulnerability and risk
      issue dictate that compulsory treatment is necessary to ensure adherence. 

PMID- 25061345
TI  - Two new species of the genus Doryphorina Melichar, 1912 (Hemiptera,
      Fulgoromorpha, Dictyopharidae) from China.
AB  - Two new species of the genus Doryphorina Melichar, 1912, D. conglobatus Zheng,
      Yang & Chen, sp. n. and D. guizhouensis Zheng, Yang & Chen, sp. n., from China
      are described and illustrated. A key is given to identify all the known species
      of Doryphorina. 

PMID- 25061346
TI  - A taxonomic revision of Limnobaris Bedel in the strict sense (Coleoptera,
      Curculionidae, Baridinae), with particular emphasis on the species found in
      China.
AB  - The genus name Limnobaris Bedel is applied in a restricted sense to baridine
      weevils with a covered pygidium and non-prominent, decussate mandibles which
      occur on sedges in the Palaearctic Region and immediately adjacent parts of
      tropical Southeast Asia. Calyptopygus Marshall and Pertorcus Voss are syn. n. of
      Limnobaris. Some species from Africa and the Americas are maintained
      provisionally in Limnobaris in the widest sense but will need to be transferred
      to other genera in future studies. A total of eleven species is recognized in
      Asia, two of which are widespread and occur also in the Western Palaearctic
      Region. Limnobaris martensi Korotyaev sp. n. is described from Nepal. Pertorcus
      tibialis basalis Voss is raised to species rank, as L. basalis (stat. prom.). New
      or reestablished synonyms are L. dolorosa (Goeze) (= L. jucunda Reitter, = L.
      koltzei Reitter), L. tibialis (Voss) (= Pertorcus tibialis pilifer Voss) and L. t
      album (Linnaeus) (= L. bedeli Reitter, = Baridius crocopelmus Gyllenhal, = L.
      sahlbergi Reitter, = L. scutellaris Reitter, = Baris t-album sculpturata Faust).
      Calandra uniseriata Dufour is considered a junior synonym of Sitophilus oryzae
      (L.) (syn. n.). A key for identification and a distribution map are provided. 

PMID- 25061347
TI  - Two new species of the Stenochinus amplus species-group from China (Coleoptera,
      Tenebrionidae, Stenochiini).
AB  - Two new species of the Stenochinus amplus species-group are described, S.
      apiciconcavus sp. n. (CHINA: Shaanxi) and S. xinyicus sp. n. (CHINA: Guangdong).
      Also, some new distribution data are provided for S. cylindricus (Gebien, 1914),
      and a key to the seven species of the S. amplus species-group from China is
      given. 

PMID- 25061348
TI  - Taxonomic review of Cratocerus Dejean, 1829 (Coleoptera, Carabidae) with the
      description of six new species.
AB  - A diagnosis of the South and Central American genus Cratocerus Dejean
      (Coleoptera: Carabidae) and a key to all species is provided. Eight species are
      recognized including six species that are newly described: Cratocerus sinesetosus
      sp. n. from French Guiana and Peru; Cratocerus multisetosus sp. n. from Costa
      Rica and Panama; Cratocerus tanyae sp. n. from Costa Rica, Guatemala, and Mexico;
      Cratocerus indupalmensis sp. n. a species widely distributed throughout Central
      and South America; Cratocerus kavanaughi sp. n. from French Guiana and Peru; and
      Cratocerus culpepperi sp. n. from Peru. A lectotype for Cratocerus sulcatus
      Chaudoir is designated. Habitus images are provided along with illustrations and
      images of male genitalia, female genitalia, and diagnostic morphological
      characters. 

PMID- 25061349
TI  - An unexpected clade of South American ground beetles (Coleoptera, Carabidae,
      Bembidion).
AB  - Phylogenetic relationships of the Antiperyphanes Complex of the genus Bembidion
      are inferred using DNA sequences from seven genes (two nuclear ribosomal, four
      nuclear protein coding, and one mitochondrial protein coding). Redefined
      subgenera within the complex are each well-supported as monophyletic. Most
      striking was the discovery that a small set of morphologically and ecologically
      heterogeneous species formed a clade, here called subgenus Nothonepha. This
      unexpected result was corroborated by the discovery of deep pits in the lateral
      body wall (in the mesepisternum) of all Nothonepha, a trait unique within
      Bembidion. These pits are filled with a waxy substance in ethanol-preserved
      specimens. In one newly discovered species (Bembidion tetrapholeon sp. n.,
      described here), these pits are so deep that their projections into the body
      cavity from the two sides touch each other internally. These structures in
      Bembidion (Nothonepha) are compared to very similar mesepisternal pits which have
      convergently evolved in two other groups of carabid beetles. The function of
      these thoracic pits is unknown. Most members of subgenus Nothonepha have in
      addition similar but smaller pits in the abdomen. A revised classification is
      proposed for the Antiperyphanes Complex. 

PMID- 25061350
TI  - A new species of Dicranocentrus (Collembola, Entomobryidae) from China with
      comments on the systematic position of the genus.
AB  - Dicranocentrus liuae sp. n. is described from the northern subtropical region of
      China. The new species is most similar to D. wangi Ma & Chen, 2007, but differs
      from it in the relatively shorter Ant. V, the 1+1 central macrochaetae on Abd.
      III, the number of chaetae on tenaculum, and the absence of dental spines. The
      systematic position of Dicranocentrus is also discussed. Present evidence,
      particularly S-chaetotaxy, indicates that the genus is closer to Heteromurus than
      to the unscaled species of Orchesella and Orchesellides. 

PMID- 25061351
TI  - The effect of latitudinal gradient on the species diversity of Chinese litter
      dwelling thrips.
AB  - To understand the global distribution patterns of litter-dwelling thrips, a total
      150 leaf litter samples were collected from 6 natural reserves located in three
      climatic regions, temperate, subtropical and tropical. The results showed the
      relative abundance of Thysanoptera was over 3.0% in 4 natural reserves from
      subtropical and tropical zone, and reached 5.9% in one tropical reserve, only
      less than Acarina and Collembola. In contrast it was only 0.3% in the warm
      temperate natural reserves, and no thrips were collected in a mid temperate
      reserve. The order on the average species numbers per plot of litter thrips was
      tropic > subtropics > temperate (n=25, p<0.05). Mean density of litter thrips per
      plots in the tropics and subtropics was significantly higher than that in the
      temperate region (n=25, p<0.05), but the average density was not significantly
      different between tropical and subtropical zones (n=25, p>0.05). The diversity of
      litter thrips in the tropics and subtropics was much higher than that in the
      temperate area based on comparsions of Shannon-Wiener diversity index (H'),
      Pielou eveness index (J), and Simpson dominance index (D). All of these results
      indicated that litter-dwelling thrips lived mainly in tropical and subtropical
      regions; meanwhile, species number and relative abundance increased with
      decreasing latitude. 

PMID- 25061352
TI  - Review of the Chinese species of the genus Varma Distant (Hemiptera,
      Fulgoromorpha, Tropiduchidae), with description of two new species.
AB  - Two new species of Varma Distant, 1906, V. falcata Chang & Chen, sp. n. (China:
      Guizhou) and V. lobata Chang & Chen, sp. n. (China: Guizhou) are described and
      illustrated. The female genitalia of four speices including two known species are
      described and illustrated for the first time. The diagnostic characters of this
      genus are redefined. A checklist to the species of Varma in China is given. The
      Keys on male and female genitalia to the Chinese species of Varma are provided. 

PMID- 25061353
TI  - A new species of Megoura (Hemiptera, Aphididae) from Japan.
AB  - A new species of the genus Megoura, M. lathyricola sp. n., was collected from
      Lathyrus japonicus subsp. japonicus (Leguminosae) in seashore areas of northern
      and southern Japan. This species is described and illustrated, and a revised key
      to the identification of the world species of Megoura is presented. 

PMID- 25061354
TI  - A new species of Zagrammosoma Ashmead (Hymenoptera, Eulophidae) from Qinghai
      Province, China.
AB  - The new species Zagrammosoma dulanense Cao & Zhu, sp. n., from Qinghai Province,
      China, is described and illustrated. All type specimens were reared from the
      pupae of Micrurapteryx sophorivora Kuznetzov & Tristan (Lepidoptera:
      Gracillariidae), a leafmining moth attacking the plant Thermopsis lanceolata R.
      Br. (Fabaceae). A key to the three known Asian species of Zagrammosoma is
      provided. All specimens are deposited in the Insect Collection, the Institute of
      Zoology, Chinese Academy of Sciences, Beijing, China. 

PMID- 25061355
TI  - Carlota, a new genus of Agrypnini from the Valdivian Forests of Chile
      (Elateridae, Agrypninae, Agrypnini).
AB  - Carlota gen. n., with one included species C. coigue sp. n., is described and
      illustrated from the Valdivian forests of Chile. The relationships of this genus
      to other Agrypnini from Chile are discussed and generic key for Chilean
      Agrypninae genera is provided. 

PMID- 25061356
TI  - Life beneath the surface of the central Texan Balcones Escarpment: genus
      Anillinus Casey, 1918 (Coleoptera, Carabidae, Bembidiini): new species, a key to
      the Texas species, and notes about their way of life and evolution.
AB  - The Texas fauna of the genus Anillinus Casey, 1918 includes three previously
      described species (A. affabilis (Brues), 1902, A. depressus (Jeannel), 1963 and
      A. sinuatus (Jeannel), 1963) and four new species here described: A. acutipennis
      Sokolov & Reddell, sp. n. (type locality: Fort Hood area, Bell County, Texas); A.
      comalensis Sokolov & Kavanaugh, sp. n. (type locality: 7 miles W of New
      Braunfels, Comal County, Texas); A. forthoodensis Sokolov & Reddell, sp. n. (type
      locality: Fort Hood area, Bell County, Texas); A. wisemanensis Sokolov &
      Kavanaugh, sp. n. (type locality: Wiseman Sink, Hays County, Texas). A key for
      identification of adults of these species is provided. The fauna includes both
      soil- and cave-inhabiting species restricted to the Balcones Fault Zone and
      Lampasas Cut Plain and adjacent areas underlain by the Edwards-Trinity Aquifer.
      Based on morphological and distributional data, we hypothesize that four lineages
      of endogean Anillinus species extended their geographical ranges from a source
      area in the Ouachita-Ozark Mountains to the Balconian region in central Texas.
      There the cavernous Edwards-Trinity aquifer system provided an excellent refugium
      as the regional climate in the late Tertiary and early Quaternary became
      increasingly drier, rendering life at the surface nearly impossible for small,
      litter-inhabiting arthropods. Isolated within the Edwards-Trinity aquifer system,
      these anilline lineages subsequently differentiated, accounting for the currently
      known diversity. The paucity of specimens and difficulty in collecting them
      suggest that additional undiscovered species remain to be found in the region. 

PMID- 25061357
TI  - Diversity and altitudinal distribution of Chrysomelidae (Coleoptera) in Peregrina
      Canyon, Tamaulipas, Mexico.
AB  - The Chrysomelidae (Coleoptera) is a highly speciose family that has been poorly
      studied at the regional level in Mexico. In the present study, we estimated
      species richness and diversity in oak-pine forest, Tamaulipan thorny scrub and in
      tropical deciduous forests in Peregrina Canyon within the Altas Cumbres Protected
      Area of the northeastern state of Tamaulipas, Mexico. Sampling of Chrysomelidae
      consisted of five sweep net samples (200 net sweeps) within each of three sites
      during four sample periods: early dry season, late dry season, early wet season,
      and late wet season. Species were identified and total numbers per species were
      recorded for each sample. A total of 2,226 specimens were collected belonging to
      six subfamilies, 81 genera and 157 species of Chrysomelidae from the study area.
      Galerucinae was the most abundant subfamily with 1,828 specimens, representing
      82.1% of total abundance in the study area. Lower abundance was recorded in
      Cassidinae (8.5%), Eumolpinae (3.6%), Cryptocephalinae (2.2%), Chrysomelinae
      (2.2%), and finally Criocerinae (1.3%). The highest species richness was also
      presented in the subfamily Galerucinae with 49% of the total obtained species
      followed by Cassidinae (20%), Cryptocephalinae (9.7%), Eumolpinae (9.7%),
      Chrysomelinae (6.5%) and Criocerinae (5.2%). The most common species were
      Centralaphthona fulvipennis Jacoby (412 individuals), Centralaphthona diversa
      (Baly) (248), Margaridisa sp.1 (219), Acallepitrix sp.1 (134), Longitarsus sp.1
      (104), Heterispa vinula (Erichson) (91), Epitrix sp.1 (84) and Chaetocnema sp.1
      (72). Twenty-two species were doubletons (1.97% of total abundance) and 52 were
      singletons (2.33%). The estimated overall density value obtained was 0.0037
      individuals/m2. The greatest abundance and density of individuals were recorded
      at the lowest elevation site. However, alpha diversity increased with increasing
      altitude. Similarity values were less than 50% among the three sites indicating
      that each site had distinct species assemblages of Chrysomelidae. The highest
      abundance was obtained during the late dry season, whereas diversity indices were
      highest during the early wet season. The present work represents the first report
      of the altitudinal variation in richness, abundance, and diversity of
      Chrysomelidae in Mexico. These results highlight the importance of conservation
      of this heterogeneous habitat and establish baseline data for Chrysomelidae
      richness and diversity for the region. 

PMID- 25061358
TI  - A review of Cunaxidae (Acariformes, Trombidiformes): Histories and diagnoses of
      subfamilies and genera, keys to world species, and some new locality records.
AB  - Cunaxidae are predaceous mites found in a variety of habitats. This work provides
      comprehensive keys to world subfamilies, genera, and species. Diagnoses and
      historical reviews are provided for subfamilies and genera. Cunaxa boneti, C.
      denmarki, C. exoterica, C. floridanus, C. lehmanae, C. lukoschusi, C. metzi, C.
      myabunderensis, C newyorkensis, C. rackae, C. reevesi, and C. reticulatus are
      moved to Rubroscirus and C. otiosus,  C. valentis, and C. rasile are returned to
      Rubroscirus. Cunaxoides neopectinatus is moved to Pulaeus. Neocunaxoides pradhani
      and N. gilbertoi are transferred to Scutopalus. Pulaeus minutus and P.
      subterraneus are moved to Lupaeus. Pseudobonzia bakari, P. malookensis, and P.
      shamshadi are transferred to Neobonzia. Dactyloscirus bifidus is transferred to
      Armascirus. Scirula papillata is reported from the Western Hemisphere for the
      first time. Armascirus ozarkensis, A. primigenius, and Dactyloscirus
      dolichosetosus are reported from new localities. 

PMID- 25061359
TI  - The intertidal polychaete (Annelida) fauna of the Sitakunda coast (Chittagong,
      Bangladesh), with notes on the Capitellidae, Glyceridae, Lumbrineridae,
      Nephtyidae, Nereididae and Phyllodocidae of the "Northern Bay of Bengal
      Ecoregion".
AB  - Of seven species of polychaetous annelids collected from the intertidal zone of
      Sitakunda coast, Chittagong, Bangladesh, five were new records for the country.
      The seven are listed, with brief notes on these, some previously recorded!
      species and others housed in the collections of the Natural History Museum,
      London. Keys are given to the recorded species of Phyllodocidae, Nereididae,
      Lumbrineridae, Nephtyidae and Capitellidae of the "Northern Bay of Bengal
      Ecoregion", and to the recognised species of Glyceridae from the Bay of Bengal.
      The worms in this Ecoregion are subject to the outflows of the Irrawaddy, Ganges,
      Hooghly and Mahanadi Rivers, and many of them are known to be freshwater
      tolerant. 

PMID- 25061360
TI  - Ecological biogeography of the terrestrial nematodes of victoria land,
      antarctica.
AB  - The terrestrial ecosystems of Victoria Land, Antarctica are characteristically
      simple in terms of biological diversity and ecological functioning. Nematodes are
      the most commonly encountered and abundant metazoans of Victoria Land soils, yet
      little is known of their diversity and distribution. Herein we present a summary
      of the geographic distribution, habitats and ecology of the terrestrial nematodes
      of Victoria Land from published and unpublished sources. All Victoria Land
      nematodes are endemic to Antarctica, and many are common and widely distributed
      at landscape scales. However, at smaller spatial scales, populations can have
      patchy distributions, with the presence or absence of each species strongly
      influenced by specific habitat requirements. As the frequency of nematode
      introductions to Antarctica increases, and soil habitats are altered in response
      to climate change, our current understanding of the environmental parameters
      associated with the biogeography of Antarctic nematofauna will be crucial to
      monitoring and possibly mitigating changes to these unique soil ecosystems. 

PMID- 25061361
TI  - Genetics and shell morphometrics of assimineids (Mollusca, Caenogastropoda,
      Truncatelloidea) in the St Lucia Estuary, South Africa.
AB  - The Assimineidae are a family of amphibious microgastropods that can be mostly
      found in estuaries and mangroves in South Africa. These snails often occur in
      great numbers and are ecologically important to the St Lucia Estuary, which forms
      a crucial part of the iSimangaliso Wetland Park, a UNESCO World Heritage Site.
      Genetic and shell morphometric analyses were conducted on individuals collected
      from nine localities distributed from the northern lake regions to the southern
      lake and the mouth of the St Lucia estuarine lake. Mitochondrial (COI) and
      nuclear (28S) DNA was used to construct Bayesian Inference, Neighbour-joining,
      Maximum Parsimony and Maximum Likelihood trees. Principal Component Analysis and
      Cluster Analysis were performed on standard shell parameter data. Results
      indicate that two different taxa are present in St Lucia. The taxon comprising
      individuals from the South Lake and St Lucia Estuary Mouth is identified as
      Assiminea cf. capensis Bartsch, in accordance with the latest taxonomic
      consensus. The taxon comprising assimineid individuals from False Bay, North Lake
      and South Lake, is here tentatively named "Assiminea" aff. capensis (Sowerby).
      These two taxa exhibit patterns of spatial overlap that appear to vary depending
      on environmental parameters, particularly salinity. The need to resolve the
      complex taxonomy of assimineids is highlighted. 

PMID- 25061362
TI  - Typhlonesticus gocmeni sp. n., a new cave-dwelling blind spider species from the
      Aegean region of Turkey (Araneae, Nesticidae).
AB  - A new species of the troglobitic spider genus Typhlonesticus is described from
      specimens found in Keloglan Cave (Denizli Province, Dodurgalar Town), Turkey.
      Typhlonesticus gocmeni sp. n. is described on the basis of both sexes; and its
      phylogenetic relationships with closely related European genera and species are
      discussed based on morphological and molecular data (the cox1, rrnL and H3
      genes). Three new combinations are proposed: Typhlonesticus idriacus (Roewer,
      1931), comb. n., Typhlonesticus morisii (Brignoli, 1975) comb. n. and
      Typhlonesticus obcaecatus (Simon, 1907), comb. n. all ex Nesticus. 

PMID- 25061363
TI  - Two new species of the genus Abrus Dai & Zhang, 2002 (Hemiptera, Cicadellidae,
      Deltocephalinae) from China.
AB  - TWO NEW SPECIES OF LEAFHOPPERS: Abrus damingshanensis sp. n. (from Guangxi) and
      A. expansivus sp. n. (from Guizhou) are described and illustrated from China. A
      map showing the geographic distribution of the two new species is given.
      Taxonomic notes on species of the genus Abrus is also provided.

PMID- 25061364
TI  - Onthophagus cervicornis Kirby, 1825, new synonym under Onthophagus dama
      (Fabricius, 1798) (Coleoptera, Scarabaeidae, Scarabaeinae).
AB  - After examining syntypes of Onthophagus cervicornis Kirby, 1825, previously
      considered to be a synonym of the North American Onthophagus striatulus (Palisot
      de Beauvois, 1809), we confirm the true identity and new synonymy under South
      Asian Onthophagus dama (Fabricius, 1798). 

PMID- 25061365
TI  - New data on the Paederus biacutus species group from mainland China (Coleoptera,
      Staphylinidae, Paederinae).
AB  - Paederus jianyueae Peng & Li, sp. n. (Zhejiang: Qingliangfeng) is described and
      illustrated. Additional records of P. biacutus Li, Zhou & Solodovnikov, 2014 and
      P. parvidenticulatus Li, Zhou & Solodovnikov, 2014 are reported. 

PMID- 25061366
TI  - A new species of Diartiger Sharp (Staphylinidae, Pselaphinae, Clavigeritae) from
      the Fengyangshan - Baishanzu Nature Reserve, East China.
AB  - A new clavigerine pselaphine, Diartiger zhejiangensis Yin & Li, sp. n., from the
      Fengyangshan - Baishanzu Nature Reserve, southern Zhejiang, is described,
      illustrated, and compared with congeners. The species is hosted by ants in the
      genus Lasius. The key to Diartiger species from China is modified to accommodate
      the new species. 

PMID- 25061367
TI  - One new species of the Clubiona obesa-group from China, with the first
      description of Clubiona kropfi male (Araneae, Clubionidae).
AB  - The present paper describes two Clubiona obesa-group species: Clubiona
      bicuspidata sp. n. and the male Clubiona kropfi Zhang, Zhu & Song, 2003, which is
      described for the first time. 

PMID- 25061368
TI  - Validation of Eustiromastix guianae (Caporiacco, 1954) (Araneae, Salticidae) with
      a first description of the female, and additions to the salticid fauna of French
      Guiana.
AB  - In this paper, we validate the doubtful species status of E. guianae, with
      redescriptions of (supposedly lost) type and holotype males, and a first
      description of the female. Both sexes are measured and illustrated by pictures of
      habitus and copulatory organs. Seventeen new salticid species for French Guiana
      are also reported and a detailed catalogue of all salticid species from the
      Trinite National Nature Reserve is provided. 

PMID- 25061369
TI  - The species of Thalerosphyrus Eaton, 1881 (Insecta, Ephemeroptera, Heptageniidae,
      Ecdyonurinae) in Java and Sumatra, with some comments on the diversity of the
      genus in the Oriental Realm.
AB  - Three species belonging to the genus Thalerosphyrus Eaton, 1881 are reported from
      Java and Sumatra. The nymphs of Th. determinatus (Walker, 1853) from Java, Th.
      sinuosus (Navas, 1933) from Java and Sumatra and Th. lamuriensis Sartori, 2014
      from Sumatra are redescribed. The egg morphology of the three species is also
      presented for the first time. A key to the nymphs is proposed. General
      considerations on the composition of the genus Thalerosphyrus in the Oriental
      Realm are given. The distribution of the genus is greatly expended, and currently
      ranges over the Himalaya and Sumbawa in the Sunda Islands. 

PMID- 25061370
TI  - A new species of Litopeltis Hebard, 1920 from Rio de Janeiro, Brazil (Blattodea,
      Blaberidae, Epilamprinae) with a key to males and geographical distribution of
      the remaining species of the genus.
AB  - This contribution describes a new species of Litopeltis from Brazil, L.
      teresopolitensis sp. n., which shows similarities with L. paineirensis Lopes &
      Oliveira, 2010 and L. ribeiropretano Lopes & Oliveira, 2010. It differs in
      characters of morphology genitalia and configuration, with the median sclerite
      bearing microspines on the sclerotic apex. A map showing the geographic
      distribution of the Brazilian species and a key to males of the other species of
      the genus are also presented. 

PMID- 25061371
TI  - Description of Ortheziolamameti tranfagliai new species (Hemiptera, Coccoidea,
      Ortheziidae) from India.
AB  - This paper describes a new Ortheziolamameti species from the Oriental region
      (India), namely Ortheziolamameti tranfagliai Konczne Benedicty, sp. n. The
      examined material was extracted from forest litter from India, using Berlese
      funnels. With this new species the genus Ortheziolamameti now includes six
      species. An identification key and distribution map are provided. 

PMID- 25061372
TI  - Identity of the leafhopper Kolla albescens, with new synonymy (Hemiptera,
      Cicadellidae).
AB  - Newly collected male and female specimens of the leafhopper Kolla albescens
      Jacobi, 1943 from the type-locality (Northeast China), are identified as
      Pagaronia albescens (Jacobi), comb. n. (Evacanthinae: Pagaroniini). A
      redescription of the species is provided together with habitus photographs of the
      male and female and illustrations of the male and female genitalia. P.
      continentalis Anufriev, 1970 is placed as a junior synonym of P. albescens syn.
      n. 

PMID- 25061373
TI  - Morphological identification of Lucilia sericata, Lucilia cuprina and their
      hybrids (Diptera, Calliphoridae).
AB  - Hybrids of Lucilia sericata and Lucilia cuprina have been shown to exist in
      previous studies using molecular methods, but no study has shown explicitly that
      these hybrids can be identified morphologically. Published morphological
      characters used to identify L. sericata and L. cuprina were reviewed, and then
      scored and tested using specimens of both species and known hybrids. Ordination
      by multi-dimensional scaling indicated that the species were separable, and that
      hybrids resembled L. cuprina, whatever their origin. Discriminant function
      analysis of the characters successfully separated the specimens into three
      unambiguous groups - L. sericata, L. cuprina and hybrids. The hybrids were
      morphologically similar irrespective of whether they were from an ancient
      introgressed lineage or more modern. This is the first evidence that hybrids of
      these two species can be identified from their morphology. The usefulness of the
      morphological characters is also discussed and photographs of several characters
      are included to facilitate their assessment. 

PMID- 25061374
TI  - CracidMex1: a comprehensive database of global occurrences of cracids (Aves,
      Galliformes) with distribution in Mexico.
AB  - Cracids are among the most vulnerable groups of Neotropical birds. Almost half of
      the species of this family are included in a conservation risk category. Twelve
      taxa occur in Mexico, six of which are considered at risk at national level and
      two are globally endangered. Therefore, it is imperative that high quality,
      comprehensive, and high-resolution spatial data on the occurrence of these taxa
      are made available as a valuable tool in the process of defining appropriate
      management strategies for conservation at a local and global level. We
      constructed the CracidMex1 database by collating global records of all cracid
      taxa that occur in Mexico from available electronic databases, museum specimens,
      publications, "grey literature", and unpublished records. We generated a database
      with 23,896 clean, validated, and standardized geographic records. Database
      quality control was an iterative process that commenced with the consolidation
      and elimination of duplicate records, followed by the geo-referencing of records
      when necessary, and their taxonomic and geographic validation using GIS tools and
      expert knowledge. We followed the geo-referencing protocol proposed by the
      Mexican National Commission for the Use and Conservation of Biodiversity. We
      could not estimate the geographic coordinates of 981 records due to
      inconsistencies or lack of sufficient information in the description of the
      locality. Given that current records for most of the taxa have some degree of
      distributional bias, with redundancies at different spatial scales, the
      CracidMex1 database has allowed us to detect areas where more sampling effort is
      required to have a better representation of the global spatial occurrence of
      these cracids. We also found that particular attention needs to be given to taxa
      identification in those areas where congeners or conspecifics co-occur in order
      to avoid taxonomic uncertainty. The construction of the CracidMex1 database
      represents the first comprehensive research effort to compile current, available
      global geographic records for a group of cracids. The database can now be
      improved by continuous revision and addition of new records. The CracidMex1
      database will provide high quality input data that could be used to generate
      species distribution models, to assess temporal changes in species distributions,
      to identify priority areas for research and conservation, and in the definition
      of management strategies for this bird group. This compilation exercise could be
      replicated for other cracid groups or regions to attain a better knowledge of the
      global occurrences of the species in this vulnerable bird family. 

PMID- 25061375
TI  - Avibase - a database system for managing and organizing taxonomic concepts.
AB  - Scientific names of biological entities offer an imperfect resolution of the
      concepts that they are intended to represent. Often they are labels applied to
      entities ranging from entire populations to individual specimens representing
      those populations, even though such names only unambiguously identify the type
      specimen to which they were originally attached. Thus the real-life referents of
      names are constantly changing as biological circumscriptions are redefined and
      thereby alter the sets of individuals bearing those names. This problem is
      compounded by other characteristics of names that make them ambiguous identifiers
      of biological concepts, including emendations, homonymy and synonymy. Taxonomic
      concepts have been proposed as a way to address issues related to scientific
      names, but they have yet to receive broad recognition or implementation. Some
      efforts have been made towards building systems that address these issues by
      cataloguing and organizing taxonomic concepts, but most are still in conceptual
      or proof-of-concept stage. We present the on-line database Avibase as one
      possible approach to organizing taxonomic concepts. Avibase has been successfully
      used to describe and organize 844,000 species-level and 705,000 subspecies-level
      taxonomic concepts across every major bird taxonomic checklist of the last 125
      years. The use of taxonomic concepts in place of scientific names, coupled with
      efficient resolution services, is a major step toward addressing some of the main
      deficiencies in the current practices of scientific name dissemination and use. 

PMID- 25061376
TI  - Contributions to the systematics of New World macro-moths V.

PMID- 25061377
TI  - The Phyllodonta latrata (Guenee) species group in Costa Rica (Geometridae,
      Ennominae).
AB  - Historically, the name Phyllodonta latrata (Guenee) has been applied to what is a
      complex of three undescribed species in Costa Rica. They are very similar in
      maculation, but can be differentiated by genitalic characters and barcodes. P.
      alajuela Sullivan, sp. n. occurs at lower altitudes in the northwestern part of
      Costa Rica whereas P. intermediata Sullivan, sp. n. and P. esperanza Sullivan,
      sp. n. are found at partially overlapping altitudes in the central mountain
      ranges. 

PMID- 25061378
TI  - The Disphragis notabilis (Schaus) species-group in Costa Rica (Lepidoptera,
      Notodontidae).
AB  - The four described taxa in the Disphragis notabilis (Schaus) species-group are
      reviewed, including the types and their dissected genitalia. Disphragis hemicera
      (Schaus), stat. rev., is elevated to species rank, D. normula (Dognin) is
      retained as a synonym of D. notabilis, D. sobolis Miller is confirmed as distinct
      from D. hemicera, and D. bifurcata sp. n., is newly described. Both D. hemicera
      and D. bifurcata occur in Costa Rica. The known ranges of the other species are
      outlined. Defining characters of each species are presented and a key to species
      is provided. Unusual variation in the genitalia is noted. 

PMID- 25061379
TI  - Four new species of Symmerista Hubner, 1816 (Notodontidae, Nystaleinae) from
      Costa Rica.
AB  - The genus Symmerista Hubner (Notodontidae, Nystaleinae) is reviewed for Costa
      Rica, based on 49 wild-caught specimens. Four species are newly described:
      Symmerista luisdiegogomezi Chacon, Symmerista inbioi Chacon, Symmerista minaei
      Chacon and Symmerista aura Chacon. All are from the cloud forests of the
      Talamanca moutain range, southern Costa Rica. Photographs of the adults, male and
      female genitalia, and barcodes are also provided. The species Symmerista tlotzin
      Schaus (1892) is removed from Symmerista and assigned to the genus Elymiotis
      Walker as a new combination. 

PMID- 25061380
TI  - The type-material of Arctiinae (Lepidoptera, Erebidae) described by Burmeister
      and Berg in the collection of the Museo Argentino de Ciencias Naturales
      Bernardino Rivadavia (Buenos Aires, Argentina).
AB  - Carlos G. Burmeister and Carlos Berg were among the most important and
      influential naturalists and zoologists in Argentina and South America and
      described 241 species and 34 genera of Lepidoptera. The Museo Argentino de
      Ciencias Naturales Bernardino Rivadavia (MACN) housed some of the Lepidoptera
      type specimens of these authors. In this study we present a catalogue with
      complete information and photographs of 11 Burmeister type specimens and 10 Berg
      type specimens of Phaegopterina, Arctiina and Pericopina (Lepidoptera, Erebidae,
      Arctiinae, Arctiini) housed in the MACN. Lectotypes or holotypes were designated
      where primary type specimens could be recognized; in some cases we were not able
      to recognize types. The catalogue also proposes nomenclatural changes and new
      synonymies: Opharus picturata (Burmeister, 1878), comb. n.; Opharus brunnea
      Gaede, 1923: 7, syn. n.; Hypocrisias jonesi (Schaus, 1894), syn. n.; Leucanopsis
      infucata (Berg, 1882), stat. rev.; Paracles argentina (Berg, 1877), sp. rev.;
      Paracles uruguayensis (Berg, 1886), sp. rev. 

PMID- 25061381
TI  - Taxonomy and biogeography of the Nearctic Raphia Hubner (Lepidoptera, Noctuidae,
      Raphiinae).
AB  - The taxonomic status and biogeography of the North American Raphia species is
      reviewed using adult morphology, larval host plants, geographic phenotypic
      variation, and variation of mtDNA COI barcode sequences. Lack of diagnostic
      morphological differences, combined with relatively low mtDNA barcode divergences
      and clinal phenotypic variation in key geographic regions indicate that the six
      previously recognized species of North American Raphia are best interpreted as
      parapatric subspecies. Raphia frater abrupta Grote, stat. n., R. f. coloradensis
      Putnam-Cramer, stat. r., R. f. piazzi Hill, stat. n., and R. f. elbea Smith,
      stat. n., are accordingly revised to subspecies of R. frater Grote. Type locality
      restrictions are provided for Raphia abrupta and Raphia frater and a neotype is
      designated for Raphia frater var. coloradensis. 

PMID- 25061382
TI  - Polyphyly of Lichen-cryptic Dagger Moths: synonymy of Agriopodes Hampson and
      description of a new basal acronictine genus, Chloronycta, gen. n. (Lepidoptera,
      Noctuidae).
AB  - The taxonomic composition and systematic position of Agriopodes Hampson is
      examined through an integrated approach using adult and larval morphology,
      biology, and molecular sequence data. The type-species of Agriopodes, Moma fallax
      Herrich-Schaffer is shown to be derived within the Acronicta grisea Walker
      species-group; accordingly, Agriopodes is relegated to synonymy under Acronicta
      Ochsenheimer, syn. n. (Acronictinae). Additionally, molecular markers and
      morphology show that Agriopodes is not monophyletic: Agriopodes tybo (Barnes) is
      not closely related to A. fallax nor to Acronicta, and is transferred to a new
      genus, Chloronycta Schmidt & Anweiler, gen. n. The immature stages of Chloronycta
      tybo comb. n. are described and illustrated for the first time. Although
      previously treated as a valid species, we show that Agriopodes geminata (Smith)
      represents the northern terminus of clinal variation in wing pattern of A. fallax
      and synonymize A. geminata under A. fallax (syn. n.). The history and identity of
      Agriopodes corticosa (Boisduval), a nomen dubium, is discussed. 

PMID- 25061383
TI  - A revision of the genus Protorthodes McDunnough with descriptions of a new genus
      and four new species (Lepidoptera, Noctuidae, Noctuinae, Eriopygini).
AB  - The genus Protorthodes McDunnough is revised to include 15 species including P.
      ustulata Lafontaine, Walsh & Ferris, sp. n., from southwestern United States, P.
      texicana Lafontaine, sp. n., from Texas and Mexico, and P. mexicana Lafontaine,
      sp. n., from Mexico. A new genus, Nudorthodes Lafontaine, Walsh & Ferris, is
      proposed for two species formerly included in Protorthodes, P. texana (Smith,
      1900), comb. n., and P. variabilis (Barnes & McDunnough, 1912), comb. n., and N.
      molino Lafontaine, Walsh & Ferris, sp. n., described from southern Arizona. A key
      to species, descriptions, illustrations of adults and genitalia, and distribution
      maps are included. 

PMID- 25061384
TI  - A new apameine genus and species from the southern Appalachian Mountains, USA
      (Lepidoptera, Noctuidae, Noctuinae).
AB  - Cherokeea gen. n. is proposed for a rarely collected apameine moth species from
      the southern Appalachian Mountains, C. attakullakulla sp. n. It is recorded from
      foothills and lower montane habitats of North Carolina and Georgia where hill
      cane, Arundinaria appalachiana Triplett, Weakley & L.G. Clark is found. Adults
      and their genitalia are figured and a mtDNA barcode sequence is given. 

PMID- 25061385
TI  - Photosymbiotic ascidians from Pari Island (Thousand Islands, Indonesia).
AB  - Photosymbiotic ascidian fauna were surveyed in the subtidal zone off Pari Island
      in the Thousand Islands (Java Sea, Indonesia). Nine species were recorded:
      Didemnum molle, Trididemnum miniatum, Lissoclinum patella, L. punctatum, L.
      timorense, Diplosoma gumavirens, D. simile, D. simileguwa, and D. virens. All of
      these species have been previously recorded in the Ryukyu Archipelago, Japan.
      Diplosoma gumavirens and D. simileguwa were originally described from the Ryukyu
      Archipelago in 2009 and 2005, respectively, and all of the observed species are
      potentially widely distributed in Indo-West Pacific coral reefs. 

PMID- 25061386
TI  - A new genus and species in the mite family Eupodidae (Acari, Eupodoidea) from
      Crimea.
AB  - A new genus Pseudoeupodes Khaustov, gen. n. and new species Pseudoeupodes porosus
      sp. n. are described from moss in Crimea. The taxonomy of the Eupodidae and some
      other families and genera of Eupodoidea is reviewed. The genus Turanopenthalodes
      Barilo, 1988 is transferred from Penthalodidae to Penthaleidae. The family
      Cocceupodidae Jesionowska, 2010 and the genus Filieupodes Jesionowska, 2010 are
      considered as junior synonyms of Eupodidae Koch, 1842 and Cocceupodes Thor, 1934,
      respectively. A key to genera of the family Eupodidae is provided. 

PMID- 25061387
TI  - First fossil record of Discocephalinae (Insecta, Pentatomidae): a new genus from
      the middle Eocene of Rio Pichileufu, Patagonia, Argentina.
AB  - A new genus and species of Discocephalini, Acanthocephalonotum martinsnetoi gen.
      n. et sp. n. is described from Rio Pichileufu, middle Eocene of Patagonia,
      Argentina at palaeolatitude ~ 46 degrees S. The new species is the first fossil
      representative of the Discocephalinae. This taxon is extant in equatorial to
      subtropical America, and some species reach warm temperate latitudes (Buenos
      Aires province). The new genus is distinguished from the other genera of
      Discocephalini by the combination of these characters: interocular width greater
      than head length; head massive and quadrangular with the anterior margin almost
      straight; juga touching each other; labrum thick and curved; triangular ante
      ocular process extending beyond the eye; broad spine-like antero-lateral process
      of the pronotum; pronotum explanate and bean shaped; scutellum triangular with a
      circular tongue reaching the anterior side of abdominal segment 7; and wings well
      developed with membrane just surpassing end of abdomen. 

PMID- 25061388
TI  - Then there were five: a reexamination of the ant genus Paratrechina (Hymenoptera,
      Formicidae).
AB  - The ant genus Paratrechina is reexamined based on the discovery of two new
      species from Madagascar (P. ankarana sp. n. and P. antsingy sp. n.). Paratrechina
      kohli, a species known from central Africa, is transferred to Paratrechina from
      Prenolepis based on a new morphological interpretation of the genus and an
      updated morphological diagnosis of the genus is provided. This means that other
      than the widespread P. longicornis, whose origins remain uncertain, all
      Paratrechina are restricted either to the Afrotropical or Malagasy regions. It
      would also appear that of the five Paratrechina species now known, three are from
      dry forest habitats. With this reexamination of the genus, the possible origins
      of P. longicornis are discussed. A key to the genera of the Prenolepis genus
      group is provided, as is a key to the workers of Paratrechina. In addition, we
      also designate a lectotype for Paratrechina kohli. 

PMID- 25061389
TI  - New records of bee flies (Diptera, Bombyliidae) from Cuatro Cienegas, Coahuila,
      Mexico.
AB  - Forty one new records of species of Bombyliidae are reported for Coahuila in
      northeastern Mexico. Nine of these species are reported for the first time for
      the country. The specimens were collected in the Cuatro Cienegas Basin and Sierra
      La Madera mountains during 2007-2013. The modified distributions of species are
      discussed. The gaps in the distribution of many species suggest an undersampling
      of this group of insects in the north of Mexico. 

PMID- 25061390
TI  - A Linnaeus NG (TM) interactive key to the Lithocolletinae of North-West Europe
      aimed at accelerating the accumulation of reliable biodiversity data
      (Lepidoptera, Gracillariidae).
AB  - We present an interactive key that is available online through any web browser
      without the need to install any additional software, making it an easily
      accessible tool for the larger public. The key can be found at
      http://identify.naturalis.nl/lithocolletinae. The key includes all 86 North-West
      European Lithocolletinae, a subfamily of smaller moths ("micro-moths") that is
      commonly not treated in field guides. The user can input data on several external
      morphological character systems in addition to distribution, host plant and even
      characteristics of the larval feeding traces to reach an identification. We
      expect that this will enable more people to contribute with reliable observation
      data on this group of moths and alleviate the workload of taxonomic specialists,
      allowing them to focus on other new keys or taxonomic work. 

PMID- 25061391
TI  - New species of Eriopeltastes Burmeister & Schaum, 1840 (Coleoptera, Scarabaeidae,
      Cetoniinae, Trichiini) from South Africa.
AB  - Both male and female of a new species of Eriopeltasttes Burmeister & Schaum,
      1840, E. (E.) ornatus Ricchiardi, sp. n., are described from the mistbelt
      grassland of KwaZulu-Natal. Sexual dimorphism is extreme in this genus, with
      females being brachypterous, fossorial and entirely black to dark brown in
      general body colour. This is only the fifth out of 12 known species in this genus
      for which the female is known. The species appears to be restricted to areas
      within or in the immediate vicinities of two marginal nature reserves, Karkloof
      and Blinkwater, in a grassland habitat that is regarded as one of the most
      threatened in the Province of KwaZulu-Natal. Despite its acknowledged importance
      as centre of endemism the area is currently in a precarious state of large-scale
      degradation. 

PMID- 25061392
TI  - Two new species of Mediomastus (Annelida, Capitellidae) from Tokyo Bay, Japan.
AB  - Two undescribed species of polychaetes in Mediomastus (Annelida: Capitellidae)
      were collected from intertidal to shallow habitats in Tokyo Bay, Japan. These are
      M. duobalteus sp. n. and M. hanedaensis sp. n. Mediomastus duobalteus sp. n. is
      distinguishable from all congeners by the following characters: 1) segments 3, 4,
      8-11 stainable with methyl green, 2) thoracic capillary chaetae unilimbate, 3)
      abdominal capillary chaetae absent, 4) paddle-like chaetae in the thorax absent,
      and 5) abdominal hooded hooks not flared. Mediomastus hanedaensis sp. n. is
      similar to M. warrenae Green, 2002, but differs from the latter in the shapes of
      the thoracic capillary chaetae and the abdominal hooded hooks, and the staining
      pattern with methyl green. In addition, a key to all Mediomastus species is
      provided. 

PMID- 25061393
TI  - A revision of the Neotropical species of Bolitogyrus Chevrolat, a geographically
      disjunct lineage of Staphylinini (Coleoptera, Staphylinidae).
AB  - The Neotropical species of the rarely collected genus Bolitogyrus (Coleoptera:
      Staphylinidae: Staphylininae: Staphylinini) are revised. The genus exhibits an
      uncommon, disjunct distribution between the Neotropical and Oriental Regions and
      is of unknown phylogenetic position within Staphylinini. Morphological evolution
      remarkable for Staphylinini was discovered within Bolitogyrus, including sexually
      dimorphic modifications of the pronotum that may be involved in male competition
      for females. rSEM interactive animations were used to establish morphological
      species boundaries between two highly variable species and are provided to
      illustrate diagnostic characters of the genitalia in unconventional views. The
      genus is redescribed based on the world fauna and twenty-eight Neotropical
      species are considered valid. Of these, nineteen are described as new to science:
      Bolitogyrus ashei sp. n.; B. apicofasciatus sp. n.; B. brevistellus sp. n.; B.
      bufo sp. n.; B. cheungi sp. n.; B. cornutus sp. n.; B. divisus sp. n.; B. falini
      sp. n.; B. gracilis sp. n.; B. inexspectatus sp. n.; B. longistellus sp. n.; B.
      marquezi sp. n.; B. newtoni sp. n.; B. pseudotortifolius sp. n.; B. pulchrus sp.
      n.; B. silex sp. n.; B. thomasi sp. n.; B. tortifolius sp. n.; and B. viridescens
      sp. n. Bolitogyrus sallei (Kraatz), stat. r. is removed from synonymy with B.
      buphthalmus (Erichson) and the following new synonyms are proposed: Cyrtothorax
      cyanescens Sharp, 1884, syn. n. = Quedius buphthalmus Erichson, 1840; C.
      nevermanni Scheerpeltz, 1974, syn. n. = C. costaricensis Wendeler, 1927. A
      summary of all available bionomic and distributional data, as well as an
      illustrated identification key to and diagnoses of all Neotropical species are
      provided. 

PMID- 25061394
TI  - Two new species of oribatid mites of Lasiobelba (Acari, Oribatida, Oppiidae) from
      Nepal, including a key to all species of the genus.
AB  - Two new species of oribatid mites of the genus Lasiobelba (Oribatida, Oppiidae),
      Lasiobelba (Lasiobelba) daamsae sp. n. and Lasiobelba (Antennoppia) nepalica sp.
      n., are described from eastern Nepal. Lasiobelba (L.) daamsae sp. n. is most
      similar to L. (L.) remota Aoki, 1959 and L. (L.) gibbosa (Mahunka, 1985),
      however, it differs from both by the anterior part of pedotecta I specifically
      curved, rostrum pointed and exobothridial setae not shorter than bothridial
      setae. Lasiobelba (Antennoppia) nepalica sp. n. is most similar to L. (A.)
      granulata (Mahunka, 1986), however, it differs from the latter by the larger body
      size, exobothridial setae longer than rostral setae and bothridial setae not
      longer than interlamellar setae. An identification key to known species of
      Lasiobelba is given. 

PMID- 25061395
TI  - Systematic and biogeographical study of Protura (Hexapoda) in Russian Far East:
      new data on high endemism of the group.
AB  - Proturan collections from Magadan Oblast, Khabarovsk Krai, Primorsky Krai, and
      Sakhalin Oblast are reported here. Twenty-five species are found of which 13
      species are new records for Russian Far East which enrich the knowledge of
      Protura known for this area. Three new species Baculentulus krabbensis sp. n.,
      Fjellbergella lazovskiensis sp. n. and Yichunentulus alpatovi sp. n. are
      illustrated and described. The new materials of Imadateiella sharovi (Martynova,
      1977) are studied and described in details. Two new combinations, Yichunentulus
      borealis (Nakamura, 2004), comb. n. and Fjellbergella jilinensis (Wu & Yin,
      2007), comb. n. are proposed as a result of morphological examination. Keys to
      species of the genera Fjellbergella and Yichunentulus are given. An annotated
      list of all species of Protura from Russian Far East is provided and discussed.
      Widely distributed species were not recorded in this area. This may be because of
      the high sensitivity of Protura to anthropogenic impact and low dispersal ability
      of the group. 

PMID- 25061396
TI  - Addition to the study of the genus Dusona (Hymenoptera, Ichneumonidae,
      Campopleginae) in Korea with description of a new species and key to the Korean
      species.
AB  - Korean species of the genus Dusona Cameron (Hymenoptera: Ichneumonidae:
      Campopleginae) are reviewed. Twenty seven species of Dusona are reported from
      South Korea, including 12 previously unrecorded species, D. bellipes (Holmgren,
      1872), D. bicoloripes (Ashmead, 1906), D. chabarowski Hinz & Horstmann, 2004, D.
      cultrator (Gravenhorst, 1829), D. japonica (Cameron, 1906), D. mactatoides Hinz,
      1994, D. scalprata Horstmann, 2004, D. sasayamae Hinz & Horstmann, 2004, D.
      oblitera (Holmgren, 1872), D. obtutor Hinz, 1994, D. auriculator Aubert, 1964, D.
      longicauda (Uchida, 1928), and a new species, D. koreana sp. n. An illustrated
      key to Korean species of Dusona provided. 

PMID- 25061397
TI  - Descriptions of three new species of the Termitophilous tribe Termitopaediini in
      China (Coleoptera, Staphylinidae, Aleocharinae).
AB  - Three new species belonging to two genera of the aleocharine tribe
      Termitopaediini Seevers, viz., Dioxeuta rara Song & Li, sp. n., D. yunnanensis
      Song & Li, sp. n., and Termitopulex sinensis Song & Li, sp. n. from Baihualing
      Natural Reserve (Southwest China: Yunnan) are described and illustrated. This is
      the first record of Termitopulex Fauvel, 1899 from China. 

PMID- 25061398
TI  - Serendipity at the Smithsonian: The 107-year journey of Rhipidocyrtus muiri Falin
      & Engel, new genus and species (Ripidiinae, Ripidiini), from jungle beast to
      valid taxon.
AB  - THE LONG AND TORTUOUS HISTORY OF AN ENIGMATIC AND RARE NEW GENUS AND SPECIES OF
      RIPIDIINE WEDGE BEETLE (RIPIPHORIDAE: Ripidiinae: Ripidiini) from Borneo is
      discussed and the taxon described and figured as Rhipidocyrtus muiri Falin &
      Engel, gen. n. and sp. n. The holotype male, and only known specimen, was
      collected 107 years ago in Borneo but subsequent to this it was transferred among
      early researchers in the early 1900s. The specimen was dissected and many
      portions slide mounted, but these were disassociated from the pinned body for
      more than a generation. A happenstance encounter led to the rediscovery and
      reassociation of the body and slide-mounted abdomen and other sclerites in 2011,
      and to its eventual description herein. Ripidiine diversity is briefly discussed
      and comparisons made between Rhipidocyrtus and other members of the subfamily. 

PMID- 25061399
TI  - Review of the genus Chrysotimus Loew from Tibet (Diptera, Dolichopodidae).
AB  - A review of the species of the genus Chrysotimus from Tibet is provided. The
      following four species are described as new to science: C. motuoensis sp. n., C.
      tibetensis sp. n., C. xuankuni sp. n., C. zhui sp. n. A key to the eight Tibetan
      species is presented. 

PMID- 25061400
TI  - Skin care: Historical and contemporary views.
AB  - Primary prevention, specifically skin care, is an important principle in Islamic
      theology just as it is emphasized in contemporary medicine. Many skin diseases
      can be prevented by a proactive approach to skin care, such as proper hygiene and
      routine inspections, principles that are constantly highlighted in the Islamic
      literature. Islam promotes primary prevention of disease, including
      recommendations for skin care practices. The recommendations for skin care
      practices in Islamic teachings are analogous to current medical guidelines. Sun
      avoidance, which is recommended by Islam, is mandatory for diseases such as
      systemic lupus erythematosus, melasma and skin cancers. Skin care and hygiene
      practices are recommended in Islam and it is considered an important mechanism
      for reducing the transmission of infections in modern medicine. The body creases
      and hair are ideal sites for malicious infestations to grow. The practice of
      "Wudu" includes washing the hands, feet, and hair with clean water. It is an
      indispensible part of daily prayers which is mandatory for every Muslim. Oral
      hygiene is also an integral part of both preventive medicine and Islamic
      teachings. Genital hygiene, particularly after urination and defecation, is
      recommended in Islamic teachings and is known to prevent urinary and vaginal
      infections in contemporary medicine. Male circumcision is an Islamic practice.
      Recently, it was proven that circumcised men are less likely to have sexually
      transmitted diseases, including HIV. This paper reviews skin care from an Islamic
      perspective and its relevance to contemporary medicine by translating the simple
      self care principles into practical guidelines in everyday use. 

PMID- 25061402
TI  - Methylphenidate vs. resperidone in treatment of methamphetamine dependence: A
      clinical trial.
AB  - BACKGROUND AND AIMS: Currently, there is no widely accepted evidence-based
      pharmacotherapy regime for the treatment of psychostimulant dependence. Yet,
      different pharmacological approaches have been tried in the treatment of MA
      addiction. The present study was conducted to compare efficiency of
      methylphenidate which is relatively easily accessible in our country, with
      resperidone for this purpose. METHODS: Eighty-six patients with MA dependence
      according to criteria defined by DSM IV-TR were divided into two groups. Patients
      in group R were given oral resperidone 1 mg daily for 1 week; then 2 mg daily in
      a divided dose for 3 weeks. Patients in group M were given oral methylphenidate
      10 mg daily for 2 weeks, 7.5 mg daily for 1 week, then 5 mg daily for 1 week.
      They were evaluated for drug craving, psychological, neurologic and somatic
      symptoms at the start and end of the study. FINDINGS: Both drugs were useful for
      lowering drug craving in patients; however resperidone was more effective (6.31
      +/- 8.31 vs.19.6 +/- 12.45 cravings per week, respectively). The effects of
      resperidone were more notable in lowering frequency and intensity of psychiatric,
      neurologic, cardiac and somatic symptoms of the patients after discontinuation of
      MA abuse; however methylphenidate was effective too; though with a lower potency.
      CONCLUSION: The present study confirmed that both methylphenidate and resperidone
      can successfully be used for treatment of MA dependence, in order to reduce drug
      craving and psychological, neurologic, and somatic problems in patients. However,
      the efficacy of methylphenidate was estimated to be less than that of resperidone
      for this purpose.

PMID- 25061401
TI  - Therapeutic approaches to drug targets in atherosclerosis.
AB  - Non-communicable diseases such as cancer, atherosclerosis and diabetes are
      responsible for major social and health burden as millions of people are dying
      every year. Out of which, atherosclerosis is the leading cause of deaths
      worldwide. The lipid abnormality is one of the major modifiable risk factors for
      atherosclerosis. Both genetic and environmental components are associated with
      the development of atherosclerotic plaques. Immune and inflammatory mediators
      have a complex role in the initiation and progression of atherosclerosis.
      Understanding of all these processes will help to invent a range of new
      biomarkers and novel treatment modalities targeting various cellular events in
      acute and chronic inflammation that are accountable for atherosclerosis. Several
      biochemical pathways, receptors and enzymes are involved in the development of
      atherosclerosis that would be possible targets for improving strategies for
      disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering
      treatments could be useful for alleviating morbidity and mortality of
      atherosclerotic cardiovascular diseases. However, novel drug targets like
      endoglin receptor, PPARalpha, squalene synthase, thyroid hormone analogues,
      scavenger receptor and thyroid hormone analogues are more powerful to control the
      process of atherosclerosis. Therefore, the review briefly focuses on different
      novel targets that act at the starting stage of the plaque form to the thrombus
      formation in the atherosclerosis. 

PMID- 25061403
TI  - Community pharmacists' attitudes toward dispensing errors at community pharmacy
      setting in Central Saudi Arabia.
AB  - PURPOSE: The main objective of this study was to survey pharmacists' attitudes
      toward dispensing errors in community pharmacy settings in Saudi Arabia. METHODS:
      A cross-sectional survey of community pharmacists in Riyadh region, Saudi Arabia
      was conducted over a period of 6 months from March through September 2012. A
      stratified random sample of eight hundred registered pharmacy practitioners was
      collected all over Riyadh region. Statistical analysis was done using SPSS
      version19.0 for windows (SPSS Inc., Chicago, Illinois). RESULTS: The response
      rate was almost 82%. The majority of the respondents are young adults (90.2%).
      The median for years of registration of respondent pharmacists was 9 years (range
      1-37 years). About 62% (407) of the respondents have a positive response while
      only 37.8% (n = 248) have a negative response in this respect. The major factors
      identified were pharmacist assistant (82.2%) and high workload (72.5%). The most
      appreciated factors that help reducing dispensing errors are improving doctors'
      hand writing and reducing work load of the pharmacist (82.9% and 82.8%
      respectively), having drug names that are distinctive (76.1%) and having more
      than one pharmacist in duty (75.5%). CONCLUSION: In conclusion, majority of
      community pharmacists indicated that the risk of dispensing errors was increasing
      and most of them were aware of dispensing errors. It is obvious from the study
      results that dispensing errors is a big concern for community pharmacy practice
      in Saudi Arabia. Therefore, there is an urgent need for the professional
      organizations and Pharmacy Boards in Saudi Arabia to determine standards for the
      profession.

PMID- 25061404
TI  - Glycemic control in diabetic patients in King Khalid University Hospital (KKUH) -
      Riyadh - Saudi Arabia.
AB  - OBJECTIVES: To evaluate glycemic control of diabetic patients at the King Khalid
      University Hospital (KKUH) in Riyadh, Saudi Arabia. METHODS: A cross sectional
      study was conducted among diabetic patients attending KKUH, Riyadh. Patients were
      identified through the hospital pharmacy records, over a one year period (January
      December, 2009). A total of 20,000 patients were identified, and 1520 patients
      were selected by a simple random method. Medical charts were reviewed, the data
      were collected in a specially designed data sheet: and entered in a computer, and
      finally analyzed using a SPSS program. RESULTS: About 90% of patients were older
      than 40 years old and 90% were overweight or obese. Fasting blood sugar was above
      7.2 mmol/L in 60% of the patients and random blood sugar was more than 10 mmol/L
      in about 70% of patients. The overall glycemic control as evaluated by HBA1C was
      acceptable in about 40% of the patients. Cholesterol level was normal in more
      than 70% of patients while triglyceride was normal in 56% of patients. In about
      half of the patients systolic blood pressure was not controlled, while in 27% the
      diastolic blood pressure was above the target level. CONCLUSION: The control of
      diabetes and its associated cardiovascular risk factors in this hospital - based
      survey, in Riyadh is far from optimal. Further studies are needed to find out the
      possible causes for this defective care of diabetic patients.

PMID- 25061405
TI  - Evaluating factors affecting the implementation of evidence based medicine in
      primary healthcare centers in Dubai.
AB  - OBJECTIVES: To assess the current evidence based medicine (EBM) knowledge,
      attitude and perceptions of physicians at Dubai Primary Health Care Sector
      (PHCS). Further to evaluate barrier and facilitator factors toward implementing
      the EBM practice. METHODOLOGY: A cross-sectional study, at Dubai PHCS, UAE
      between June and August 2010. The survey was composed of two phases. The first
      phase was a self administrated questionnaire employed for data collection and the
      second phase was qualitative method, which was in the form of individual
      interviews. Statistical Package for Social Sciences (SPSS) was used for data
      analysis. RESULTS: In total 48 participants responded to the survey questionnaire
      and 13 responded to individual interviews. The response rate was 70.0%. Mean age
      was 42.18 (SD 10.46). The majority were females (64.6%). The physicians who
      attended EBM courses reported 70.30% using EBM and showed statistical
      significance (p = 0.002) from those who did not attend the EBM courses. 65.0%
      believe that 50-75% of the patients are capable of participating in clinical
      decision while 71.8% disagreed that the concept of EBM is not applicable to their
      culture. In addition they showed significance (p = 0.03) between physician
      beliefs with regard to patient capacity to take decision. About 67.0% of the
      family physicians were knowledgeable and followed systematic review as the
      strongest evidence. They had no access to the EBM resources (37.0%) and had no
      time to practice the EBM (38.0%). Nearly 40.0% interviewees reported lack of
      encouragement to attend EBM courses. EBM activities (22.0%) and active audit
      (18.0%) were top rated facilitating factors. CONCLUSIONS: EBM is not fully
      utilized by indefinite physicians in the Dubai PHC sector. Factors associated
      with non-utilization of EBM in the PHCS are lack of encouragement to attend EBM
      courses, senior physicians resist adoption of EBM, lack of time and insufficient
      dissemination process for implementing the clinical guideline.

PMID- 25061406
TI  - Saudi school students' knowledge, attitude and practice toward medicines.
AB  - The current study was aimed to assess Saudi school students' knowledge, attitude
      and practice about medicines. A pretested self-administered questionnaire was
      used anonymously among 15-20 year-old adolescents attending tertiary schools in
      Taif City, KSA. A total of 1022 students completed the questionnaires. Only 15.4%
      of the respondents knew the medicines' uses. Most of the students 79.6% affirmed
      that they used to take medicines after consulting physicians, and 45.1% of the
      students thought that tablet size affects the medicine's efficacy. More than half
      of the students knew that high temperatures affect the efficacy of medicines,
      there was a significant difference between rural and urban areas (P = 0.005).
      Physicians (50.6%) and community pharmacists (15.7%), were the main students'
      reliable sources of information about medicines. The majority of the students
      70.5% were interested in learning more about medicines. The younger students ?18
      years wish to learn more than the older ones (P < 0.014). The study showed that
      Saudi school students aged 15-20 years old have poor knowledge, misconception and
      negative attitudes about medicines. Low level of knowledge may expose adolescents
      to health-related problems. Educational efforts are important to improve
      students' practice toward medicines. 

PMID- 25061407
TI  - Nanoprecipitation is more efficient than emulsion solvent evaporation method to
      encapsulate cucurbitacin I in PLGA nanoparticles.
AB  - Cucurbitacin I is a hydrophobic molecule that exerts a degree of polarity, which
      is expected to complicate its loading in PLGA nanoparticles by the classical
      emulsion solvent evaporation technique. In the current study, variants of
      emulsion solvent evaporation method were used to prepare PLGA nanoparticles of
      cucurbitacin: CI-NP1 (single emulsion starting with 1000 MUg drug), CI-NP2
      (double emulsion starting with 250 MUg drug), and CI-NP3 (double emulsion
      starting with 500 MUg drug). On the other hand, CI-NP4 was prepared by
      nanoprecipitation (starting with 1000 MUg drug). In CI-NP1, cucurbitacin I
      encapsulation efficiency (EE) was 1.29%. The employment of double emulsion, in CI
      NP2 and CI-NP3, increased cucurbitacin I EE to 4.8% and 7.96%, respectively.
      Nanoprecipitation significantly increased the EE of cucurbitacin I to 48.79% in
      CI-NP4. It is likely that cucurbitacin I escapes with the organic solvent after
      the emulsification step to the aqueous phase leading to ineffective entrapment in
      the polymeric matrix. Avoiding emulsification seems efficient in increasing
      cucurbitacin I disposition in the instantly-precipitating NPs. Therefore,
      nanoprecipitation method increases cucurbitacin I entrapment in PLGA NPs and
      possibly other water-insoluble polar drugs. 

PMID- 25061408
TI  - Engineering erythrocytes as a novel carrier for the targeted delivery of the
      anticancer drug paclitaxel.
AB  - Paclitaxel (PTX) is formulated in a mixture of Cremophor EL and dehydrated
      alcohol. The intravenous administration of this formula is associated with a risk
      of infection and hypersensitivity reactions. The presence of Cremophor EL as a
      pharmaceutical vehicle contributes to these effects. Therefore, in this study, we
      used human erythrocytes, instead of Cremophor, as a pharmaceutical vehicle. PTX
      was loaded into erythrocytes using the preswelling method. Analysis of the
      obtained data indicates that 148.8 MUg of PTX was loaded/mL erythrocytes, with an
      entrapment efficiency of 46.36% and a cell recovery of 75.94%. Furthermore, we
      observed a significant increase in the mean cell volume values of the
      erythrocytes, whereas both the mean cell hemoglobin and the mean cell hemoglobin
      concentration decreased following the loading of PTX. The turbulence fragility
      index values for unloaded, sham-loaded and PTX-loaded erythrocytes were 3, 2, and
      1 h, respectively. Additionally, the erythrocyte glutathione level decreased
      after PTX loading, whereas lipid peroxidation and protein oxidation increased.
      The release of PTX from loaded erythrocytes followed first-order kinetics, and
      about 81% of the loaded drug was released into the plasma after 48 h. The results
      of the present study revealed that PTX was loaded successfully into human
      erythrocytes with acceptable loading parameters and with some oxidative
      modification to the erythrocytes. 

PMID- 25061409
TI  - Design of liposomal colloidal systems for ocular delivery of ciprofloxacin.
AB  - Ophthalmic drug bioavailability is limited due to protective mechanisms of the
      eye which require the design of a system to enhance ocular delivery. In this
      study several liposomal formulations containing ciprofloxacin (CPX) have been
      formulated using reverse phase evaporation technique with final dispersion of pH
      7.4. Different types of phospholipids including Phosphatidylcholine,
      Dipalmitoylphosphatidylcholine and Dimyristoyl-sn-glycero-3-phosphocholine were
      utilized. The effect of formulation factors such as type of phospholipid,
      cholesterol content, incorporation of positively charging inducing agents and
      ultrasonication on the properties of the liposomal vesicles was studied.
      Bioavailability of selected liposomal formulations in rabbit eye aqueous humor
      has been investigated and compared with that of commercially available CPX eye
      drops (Ciprocin(r)). Pharmacokinetic parameters including Cmax, Tmax, elimination
      rate constant, t1/2, MRT and AUC0-infinity, were determined. The investigated
      formulations showed more than three folds of improvement in CPX ocular
      bioavailability compared with the commercial product. 

PMID- 25061410
TI  - A novel approach to formulation factor of aceclofenac eye drops efficiency
      evaluation based on physicochemical characteristics of in vitro and in vivo
      permeation.
AB  - The purpose of the present study was to evaluate aceclofenac eye drop through
      excised goat cornea. Raising pH of the formulation from 6.0 to 8.0, effect of
      different preservatives or effect of viscosity enhancer decreases apparent
      permeability coefficient. Topical ophthalmic NSAID are used to treat ocular
      surface and anterior segment inflammation as well as post operative management of
      pain and inflammation. Aceclofenac's unique chemical structure makes it both a
      potent anti inflammatory drug and lipophilic molecule that penetrates ocular
      tissue, ensuring relief of pain in cataract and refractive surgery and corneal
      abrasion. The octanol/water partition coefficient of aceclofenac drug is 1.86 +/-
      0.75. Permeation characteristics of the drug were evaluated by putting 1 ml
      formulation on freshly excised goat cornea fixed between donor and receptor
      compartments of an all-glass modified Franz diffusion cell and measuring the drug
      permeated in the receptor by spectrophotometry at 275 nm, after 120 min. The
      results suggest that aceclofenac ophthalmic solution (pH 7) containing BAC
      provides increased in vitro ocular availability through goat corneas. The
      combination of methyl paraben and propyl paraben MP-PP preservative in
      aceclofenac ophthalmic eye drop 0.1% formulated in phosphate buffer increases
      transcorneal permeation. The developed formulations were evaluated for their
      pharmacodynamics in albino rabbits, by measuring in-vivo study and were compared
      to a marketed voltrane ophthalmic solution. 

PMID- 25061411
TI  - Evaluation of the hepatroprotective and nephroprotective activities of
      Scrophularia hypericifolia growing in Saudi Arabia.
AB  - The hepatroprotective and nephroprotective effects of the ethanol extract of the
      aerial parts of Scrophularia hypericifolia growing in Saudi Arabia were evaluated
      at 250 and 500 mg kg(-1) doses using Wistar albino rats as experimental animal
      model. Toxic doses of paracetamol were used to induce liver and kidney
      toxicities, while the standard drug silymarin was used as reference. The
      biochemical parameters such as aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase
      (GGT) and total bilirubin were estimated as reflections of the liver condition.
      Kidney condition was investigated through measurement of serum urea, serum
      creatinine, sodium and potassium levels. Liver and kidney samples of rats treated
      with 500 mg kg(-1) of the extract were subjected to the histopathological study.
      The ethanol extract of the aerial parts of S. hypericifolia showed dose dependent
      moderate level of protection against paracetamol induced hepatrotoxicity and
      nephrotoxicity as indicated from the obtained results. The reduction of the
      sodium and potassium levels by the higher dose of the extract exceeded that
      obtained by silymarin. 

PMID- 25061412
TI  - Combating oxidative stress as a hallmark of cancer and aging: Computational
      modeling and synthesis of phenylene diamine analogs as potential antioxidant.
AB  - The cross talk between the over expression of oxygen-free radicals is known as
      reactive oxygen species (ROS) that is associated with the excessive telomerase
      activity (TA). Telomerase activity is an invariable finding where human
      telomerase (hTERT) has been implicated in tumor oxidative stress and redox
      mediated malignancy. The hTERT over expression is a novel tumor marker and is
      promising as a novel class of therapeutic weapons to fight against cancer. A new
      series of phenylene diamines were designed, synthesized, and evaluated for their
      in vitro antioxidant as an indicator of inhibiting the oxidative stress tumor.
      Compounds 3b and 7b proved to be the most active antioxidants with high
      percentage ABTS inhibition ranged from 89.40% to 88.59% respectively. Molecular
      modeling studies indicated that the crest configuration of phenylene diamine
      nucleus with substitutions of trimethoxy benzamido functional proved to be
      crucial for enhancing the free radical scavenging activity. Molecular modeling
      exploration indicated the proper binding selectivity of the 3b and 7b to the 3KYL
      pocket with promising hTERT inhibitors as a hallmark of cancer. 

PMID- 25061413
TI  - Plackett-Burman randomization method for Bacterial Ghosts preparation form E.
      coli JM109.
AB  - Plackett-Burman randomization method is a conventional tool for variables
      randomization aiming at optimization. Bacterial Ghosts (BGs) preparation has been
      recently established using methods other than the E lysis gene. The protocol has
      been based mainly on using critical concentrations from chemical compounds able
      to convert viable cells to BGs. The Minimum Inhibition Concentration (MIC) and
      the Minimum Growth Concentration (MGC) were the main guide for the BGs
      preparation. In this study, Escherichia coli JM109 DEC has been used to produce
      the BGs following the original protocol. The study contained a detail protocol
      for BGs preparation that could be used as a guide. 

PMID- 25061414
TI  - Spatial and Temporal Dynamics of Flora in Forest, Grassland and Common Land
      Ecosystems of Western Chitwan, Nepal.
AB  - This paper describes changes of species composition and population of flora in
      space and time in western Chitwan, Nepal. This paper also discusses on the
      changes in flora due to flood and human activities. To illustrate these changes,
      we used survey data collected from January to April of 1996, 2000, and 2007 from
      the Barandabhar forest, National Park forest and the forests along the Narayani
      River banks, grasslands of National Park and common lands of western Chitwan as a
      part of longitudinal study on "reciprocal relation of population and the
      environment". From these data, density values were calculated to analyze spatial
      and temporal changes in flora species composition and population. We also noted
      the changes of top species in time and space in due course of time. If the
      species and its rank not changed, their densities (population) values of flora
      species changed. We found that changes in species composition, population,
      appearance or disappearance of flora from a particular space (research plot) were
      noted as a result of natural forces or human activities.

PMID- 25061415
TI  - Editorial.

PMID- 25061416
TI  - Correlation between magnetic resonance imaging and physical exam in assessment of
      injuries to posterolateral corner of the knee.
AB  - OBJECTIVE: Evaluate the correlation between magnetic resonance imaging, clinical
      examination and intraoperative identification of posterolateral corner injuries
      of the knee. METHODS: We compared the findings of physical examination under
      anesthesia and intraoperative findings as the gold standard for the
      posterolateral corner injury with the reports of the MRIs of patients who
      underwent reconstruction of the posterolateral corner. Thus, we evaluated the use
      of MRI for the diagnosis of lesions. RESULTS: We found a sensitivity of 100% in
      lesions of the anterior cruciate ligament (ACL), 86.96% in lesions of the
      posterior cruciate ligament (PCL), 57.58% in lesions of the lateral collateral
      ligament (LCL) and 24.24 % in tendon injuries of the popliteal muscle (PMT).
      CONCLUSION: Posterolateral corner injury is difficult to visualize and interpret;
      therefore, MRI imaging should not be used alone for diagnosis.

PMID- 25061417
TI  - Common injuries in athletes' knee: experience of a specialized center.
AB  - OBJECTIVE: The present cross-sectional study aims to identify the most common
      knee injuries in athletes cared at a Specialized Outpatient Clinics. METHOD:
      Analysis of patients cared at the Knee Outpatient Clinics of a Sports Trauma
      Center, divided by gender, age and diagnosed injury. RESULTS: Initially 440
      patients were divided into 33 types of sports; after excluding the less
      statistically significant practices, nine sports remained. The most frequently
      performed sports were football with almost 50% of total patients presenting
      anterior cruciate ligament (ACL) injury, and road runs with great frequency of
      meniscal injury. There was no correlation of the disorder with the type of sports
      performed but a correlation was found with patient's age/gender. CONCLUSION: The
      complete ACL rupture was the most common injury found in football, basketball and
      volleyball players, followed by meniscal injury in street runners.

PMID- 25061418
TI  - Effectiveness of histology and cytology on musculoskeletal tumor diagnosis.
AB  - OBJECTIVE: To compare cytology and histology on the diagnosis of musculoskeletal
      neoplasms. METHOD: Fifty eight cases available to evaluation were analyzed both
      by cytology and histology. The results of the biopsies studied by histology and
      cytology were compared to the results obtained on the surgical specimen or
      immunohistochemistry. We determined the percentage of correct results,
      sensitivity, specificity, positive and negative predictive values and accuracy of
      each method. RESULTS: Twelve per cent of biopsies were inconclusive by cytology.
      The percentage of correct diagnosis was 70.7% and 81% (p=.179), the ability to
      differentiate benign lesions from malignant ones was 84.5% and 93.1% (p=0.18)
      respectively, for cytology and histology. Cytology showed sensitivity of 87.8%,
      specificity of 76.5%, positive predictive value of 90%, negative predictive value
      of 72% and accuracy 84.5%. Histology showed sensitivity of 90.2%, specificity of
      100%, positive predictive value of 100%, negative predictive value of 81% and
      accuracy of 93.1%. The Youden index for cytology was 64.3% and for histology it
      was 90.2%. CONCLUSION: Despite promising, cytology obtained by thin needle
      aspiration is less accurate and reliable than the histological evaluation on
      musculoskeletal tumors diagnosis.

PMID- 25061419
TI  - Obesity, ostearthritis and clinical treatment.
AB  - OBJECTIVE: To evaluate the relationship between BMI and pain and function in
      patients with OA undergoing medical treatment following OARSI recommendations.
      METHODS: Thirty-eight patients were classified according to their arthritis
      degree by X-ray and body mass index (BMI). All patients completed the WOMAC,
      Lequesne, and visual analogue pain scale (VAS) questionnaires at baseline and
      after six months treatment. All patients were treated with diacerhein and
      analgesics (according to pain), orthotics (when indicated), and an educational
      program on osteoarthritis. They were instructed on balanced diet and exercise at
      least three times a week. RESULTS: There was no significant BMI variation in this
      study. The higher the initial BMI, the lower the improvement in pain (p = 0.03).
      Pain did not improve significantly (p = 0.2). Function improved (p <0.001) in
      inverse ratio to the initial BMI. CONCLUSION: BMI determines how patients will
      improve pain and function.

PMID- 25061420
TI  - Flexor hallux tendon transfer: comparative study through double or single
      approach.
AB  - OBJECTIVE: To quantify the FHL length difference obtained through a single
      approach and by a double combined approach. METHODS: 16 fresh cadavers, a total
      of 32 feet, were used to measure the FHL graft length. With the cadaver
      positioned in ventral decubitus, a posteromedial incision in the ankle and a
      second incision in the plantar cavus were performed. RESULTS: The average gain of
      tendon's length (GTL) was of 42.43 mm, the lowest value being 32 mm and the
      largest 48 mm. The comparative analysis of the GTL on the right and left sides
      through the paired "t" Test does not show statistical differences, with a p-value
      = 0.463 and a statistical power of 0.1443. The height analysis of the sample and
      the right and left GTL performed through linear regression do not show
      statistically significant differences, with a p-value of 0.38311 and 0.82640,
      respectively. CONCLUSION: Harvesting the FHL graft using a double combined
      approach yields a 42.43 mm length gain in comparison to harvesting using the
      single approach.

PMID- 25061421
TI  - Arthroscopic study of injuries in articular fractures of distal radius extremity.
AB  - OBJECTIVE: To analyze the incidence of wrist ligament and cartilage associated
      fractures of the distal radius, through arthroscopy, correlating with AO/ASIF
      classification. METHODS: Thirty patients aged between 20 and 50 years old, with
      closed fracture from groups B and C according to AO/ASIF classification were
      selected. All of them were submitted to wrist arthroscopy to address intra
      articular injuries and reduction and osteosynthesis of the fracture. RESULTS: A
      high incidence of intra-articular injuries was noticed, and 76.6% of them
      presented injury of the triangular fibrocartilage complex, 36.6% of the intrinsic
      scapholunate ligament, 6.6% of the intrinsic triquetrolunate ligament, and 33%
      articular cartilage injury larger than three millimeters. Patients with fractures
      from type C according to AO/ASIF classification presented a higher incidence of
      ligament injuries. CONCLUSION: There is no relationship between the presence of
      chondral injury and the AO/ASIF classification of the fractures in the cases
      reported in this study.

PMID- 25061422
TI  - Epidemiology of traumatic hip dislocation in patients treated in Ceara, Brazil.
AB  - OBJECTIVE: To describe the epidemiological profile of patients with traumatic hip
      dislocation treated in our Institute from November/2012 to July/2013. METHODS: A
      descriptive cross-sectional study based on interviews and involving 43 patients
      who suffered traumatic hip dislocation was conducted. RESULTS: The mean age of
      patients was 34.4 years old and 90.7% were male. Regarding the mechanism of
      injury, 95% involved traffic accidents. The posterior dislocation of the hip was
      the most common injury (93%). Associated lesions were observed in 74.4% of
      patients, hip fractures being the most frequent. The time span between accident
      and dislocation reduction was less than 6 hours in 37.2% of patients, between 6
      and 12 hours in 32.5% and over 12 hours in 30.3%, ranging from 1 hour to 15 days.
      A fraction of 90.7% of patients was submitted to closed reduction. CONCLUSION:
      Traumatic hip dislocation affected mostly young adults, victims of traffic
      accidents. The posterior dislocation of the hip was the most frequent injury and
      closed reduction was performed in 90.7% of patients. The time span between
      accident and dislocation reduction was less than 12 hours in most patients.

PMID- 25061423
TI  - Mechanical analysis of femoral neck fracture fixation in synthetic bone.
AB  - OBJECTIVE: To analyze statistically results obtained between biomechanical assays
      on fixation of femoral neck fracture type Pauwels III, on synthetic bone, using
      7.5 mm non parallel cannulated screws and control group. METHODS: Ten synthetic
      bones from a national brand were used. Test group: fixation of 70((o)) tilt
      femoral neck osteotomy was performed using three 7.5 mm non parallel cannulated
      screws. We analyzed the resistance of this fixation with 5 mm of displacement,
      and rotational deviation (phase 1) and with 10 mm offset (phase 2). CONTROL
      GROUP: the models were tested in their integrity until the femoral neck fracture
      occurred. RESULTS: the values of the test group in phase 1, in sample 1-5 had a
      mean of 517N and SD = 96N. Rotational deviations showed a mean of 3.79 degrees  e
      SD = 2. 03 degrees . In phase 2, mean was 649N and SD = 94N. The values of the
      maximum load in the control group were: 1544N, 1110N, 1359N, 1194N, 1437N;
      respectively. Statistical analysis between the groups showed a statistically
      significant lower value in the test group. CONCLUSION: the analysis of mechanical
      resistance between the groups has determined statistically significant value for
      the test group.

PMID- 25061424
TI  - Internal fixators: a safe option for managing distal femur fractures?
AB  - OBJECTIVE: Evaluate safety and reliability of internal fixator for the treatment
      of intra-articular and periarticular distal femur fractures. METHODS:
      Retrospective data evaluation of 28 patients with 29 fractures fixed with
      internal fixator was performed. There was a predominance of male patients
      (53.5%), with 52% of open wound fractures, 76% of AO33C type fractures, and a
      mean follow up of 21.3 months. Time of fracture healing, mechanical axis
      deviation, rate of infection and postoperative complications were registered.
      RESULTS: Healing rate was 93% in this sample, with an average time of 5.5 months.
      Twenty-seven percent of patients ended up with mechanical axis deviation, mostly
      resulting from poor primary intra-operative reduction. There were two cases of
      implant loosening; two implant breakage, and three patients presented stiff knee.
      No case of infection was observed. Healing rate in this study was comparable with
      current literature; there was a high degree of angular deviation, especially in
      the coronal plane. CONCLUSION: Internal fixators are a breakthrough in the
      treatment of knee fractures, but its use does not preclude application of
      principles of anatomical articular reduction and mechanical axis restoration.

PMID- 25061425
TI  - Prevalence of falls in fibromyalgia patients.
AB  - OBJECTIVE: To compare the risk of falls in fibromyalgia (FM) patients compared to
      rheumatoid arthritis (RA) patients and normal controls. METHODS: We studied 60
      FM, 60 RA patients and 60 controls for fall frequency in one week, one month, six
      months and one year. Patients were submitted to body mass index determination and
      balance evaluation through the Berg scale. Data on disease impact and depression
      were collected in FM patients through the Fibromyalgia Impact Questionnaire (FIQ)
      and the Beck Questionnaire. RESULTS: FM patients had a higher frequency of falls
      than RA patients and control individuals in one month (p<0.0001), in six months
      (p<0.0001) and in one year (p<0.0001). No relationship was found between falls
      and body mass index, pain or depression scores. Falls in 12 months were
      associated with higher FIQ values. CONCLUSION: FM patients fall more often than
      RA patients and control individuals.

PMID- 25061426
TI  - Gender differences in sore throat and hoarseness following endotracheal tube or
      laryngeal mask airway: a prospective study.
AB  - BACKGROUND: Postoperative sore throat and hoarseness are common minor
      complications following airway manipulation. This study was primarily done to
      determine gender differences in the incidence of these symptoms and the location
      of POST after laryngeal mask airway (LMA) and endotracheal tube (ETT). METHODS: A
      total of 112 men and 185 women were included during a four month period. All
      patients were evaluated postoperatively and after 24 hours about the occurrence
      of sore throat, its location and hoarseness. If the patients had any symptom,
      they were followed-up at 48, 72 and 96 hours until the symptoms resolved.
      RESULTS: There was no significant gender difference in postoperative sore throat
      (POST) and postoperative hoarseness (PH) when analyzing both airway devices
      together. The incidence of sore throat and hoarseness were higher postoperatively
      after an ETT than an LMA (32% vs. 19%, p = 0.012) and 57% vs. 33% (p < 0.001)
      respectively. Significantly more women than men had POST after an LMA (26% vs.
      6%, p = 0.004). No significant gender difference was found in either POST or PH
      after an ETT or in the incidence of PH after an LMA. More patients located their
      pain below the larynx after an ETT vs. an LMA (24% vs. 4%). Pain above the larynx
      was more common after an LMA than an ETT (52% vs. 37%). CONCLUSIONS: In a
      clinical setting where women are intubated with a smaller size ETT than men,
      there were no significant differences in POST or PH between genders.
      Additionally, more women than men have POST when an LMA is used. Awareness of
      POST and PH may help streamline patients in whom the best airway device could be
      used during anesthesia and surgery.

PMID- 25061427
TI  - Relationship between intraoperative regional cerebral oxygen saturation trends
      and cognitive decline after total knee replacement: a post-hoc analysis.
AB  - BACKGROUND: Bilateral regional brain oxygen saturation (rSO2) trends, reflecting
      intraoperative brain oxygen imbalance, could warn of brain dysfunction. Various
      types of cognitive impairment, such as memory decline, alterations in executive
      function or subjective complaints, have been described three months after
      surgery. Our aim was to explore the potential utility of rSO2 values as a warning
      sign for the development of different types of decline in postoperative
      psychological function. METHODS: Observational post-hoc analysis of data for the
      patient sample (n = 125) of a previously conducted clinical trial in patients
      over the age of 65 years undergoing total knee replacement under spinal
      anesthesia. Demographic, hemodynamic and bilateral rSO2 intraoperative values
      were recorded. An absolute rSO2 value of <50% or a reduction of >20% or >25%
      below baseline were chosen as relevant cutoffs. Composite function test scores
      were created from baseline to three months for each patient and adjusted for the
      mean (SD) score changes for a control group (n = 55). Tests were used to assess
      visual-motor coordination and executive function (VM-EF) (Wechsler Digit Symbol
      Coding and Visual Reproduction, Trail Making Test) and memory (Auditory Verbal
      Learning, Wechsler Memory Scale); scales were used to assess psychological
      symptoms. RESULTS: We observed no differences in baseline rSO2 values; rSO2
      decreased significantly in all patients during surgery (P < 0.0001). Seventy-five
      patients (60%) had no sign of cognitive decline or psychological symptoms. Twenty
      one patients (16.8%) had memory decline, 3 (2.4%) had VM-EF decline, and 33
      (26.4%) had psychological symptoms. Left and right rSO2 values were asymmetric in
      patients who had memory decline (mean [SD] left-right ratio of 95.03 [8.51] vs
      101.29 [6.7] for patients with no changes, P = 0.0012). The mean right-left
      difference in rSO2 was also significant in these patients (-2.87% [4.73%], lower
      on the right, P = 0.0034). CONCLUSIONS: Detection of a trend to asymmetry in rSO2
      values can warn of possible postoperative onset of memory decline. Psychological
      symptoms and memory decline were common three months after knee replacement in
      our patients over the age of 65 years.

PMID- 25061428
TI  - Dynamic changes of urinary proteins in a focal segmental glomerulosclerosis rat
      model.
AB  - BACKGROUND: In contrast to blood, which has mechanisms to maintain a homeostatic
      internal environment, urine is more likely to reflect changes in the body. As
      urine accumulates all types of changes, identifying the precise cause of changes
      in the urine proteome is challenging and crucial in biomarker discovery. To
      reduce the effects of both genetic and environmental factors on the urinary
      proteome, this study used a rat model of adriamycin-induced nephropathy
      resembling human focal segmental glomerulosclerosis (FSGS) development. RESULTS:
      Urine samples were collected at before adriamycin administration and day3, 7, 11,
      15 and 23 after. Urinary proteins were profiled by liquid chromatography coupled
      with tandem mass spectrometry (LC-MS/MS). Of 23 changed proteins with disease
      development, 20 have human orthologs, and 13 proteins were identified as stable
      in normal human urine, meaning that changes in these proteins are more likely to
      reflect disease. Fifteen of the identified proteins have not been established to
      function in FSGS development. Seven proteins were selected for verification in
      ten more rats as markers closely associated with disease severity by western
      blot. CONCLUSION: We identified proteins changed in different stages of FSGS in
      rat models, which may aid in biomarker development and the understanding of FSGS
      pathogenesis.

PMID- 25061429
TI  - The multiple sclerosis self-management scale: clinicometric testing.
AB  - BACKGROUND: The Multiple Sclerosis Self-Management Scale (MSSM) is currently the
      only measure that was developed specifically to address self-management among
      individuals with multiple sclerosis (MS). While good internal consistency (alpha
      = 0.85) and construct validity have been demonstrated, other psychometric
      properties have not been established. This study was undertaken to evaluate the
      criterion validity, test-retest reliability, and face validity of the MSSM.
      METHODS: Thirty-one individuals with MS who met the inclusion criteria were
      recruited to complete a series of questionnaires at two time points. At Time 1,
      participants completed the MSSM and two generic self-management tools-the
      Partners in Health (PIH-12) and the Health Education Impact Questionnaire (heiQ)
      as well as a short questionnaire to capture participants' opinions about the
      MSSM. At Time 2, approximately 2 weeks after Time 1, participants completed the
      MSSM again. RESULTS: The available MSSM factors showed moderate to high
      correlations with both PIH-12 and heiQ and were deemed to have satisfactory test
      retest reliability. Face validity pointed to areas of the MSSM that need to be
      revised in future work. As indicated by the participants, some dimensions of MS
      self-management are missing in the MSSM and some items such as medication are
      redundant. CONCLUSIONS: This study provides evidence for the reliability and
      validity of the MSSM; however, further changes are required for both researchers
      and clinicians to use the tool meaningfully in practice.

PMID- 25061430
TI  - Treatment satisfaction in multiple sclerosis.
AB  - BACKGROUND: Disease-modifying therapies (DMTs) for the treatment of multiple
      sclerosis (MS) are associated with inconvenient methods of administration,
      significant side effects, and low adherence rates. This study was undertaken to
      compare treatment satisfaction in MS patients treated with interferon beta-1a
      intramuscular (IFNbeta-1a IM), interferon beta-1a subcutaneous (IFNbeta-1a SC),
      glatiramer acetate (GA), and natalizumab (NTZ), and to examine the associations
      between treatment satisfaction ratings and adherence to therapy. METHODS: Two
      hundred twenty-six treated MS patients completed the Treatment Satisfaction
      Questionnaire for Medicine. Multivariable models were used to compare treatment
      satisfaction across groups. RESULTS: There were no statistically significant
      differences in overall treatment satisfaction. The NTZ group reported greater
      satisfaction with the ability of the medication to treat or prevent MS than the
      IFNbeta-1a IM group. The NTZ group also reported higher overall convenience
      scores than the IFNbeta-1a IM group and greater satisfaction with ease of use of
      the medication than the interferon and GA groups. Patients in the IFNbeta-1a IM
      group reported less satisfaction with ease of planning when to use the medication
      than those in the other groups. Convenience was associated with adherence in
      IFNbeta-1a SC- and GA-treated patients, with lower convenience scores associated
      with lower adherence. CONCLUSIONS: These results may be useful to MS patients and
      health-care providers facing decisions about DMT use.

PMID- 25061431
TI  - Short-term effect of aerobic exercise on symptoms in multiple sclerosis and
      chronic fatigue syndrome: a pilot study.
AB  - BACKGROUND: This pilot study was conducted to determine whether a 15-minute bout
      of moderate-intensity aerobic cycling exercise would affect symptoms (pain and
      fatigue) and function (Timed 25-Foot Walk test [T25FW] and Timed Up and Go test
      [TUG]) in people with multiple sclerosis (MS) or chronic fatigue syndrome (CFS),
      and to compare these results with those of a healthy control group. METHODS:
      Eight people with MS (Expanded Disability Status Scale score 5-6; Karnofsky score
      50-80), eight people with CFS (Karnofsky score 50-80), and eight healthy
      volunteers participated in the study. Pain and fatigue levels and results of the
      T25FW and TUG were established at baseline as well as at 30 minutes, 2 hours, and
      24 hours following a 15-minute stationary cycling aerobic exercise test. Repeated
      measures analysis of variance (ANOVA) and covariance (ANCOVA) were used to
      analyze the findings over time. RESULTS: At baseline there were statistically
      significant differences between groups in fatigue (P = .039), T25FW (P = .034),
      and TUG (P = .010). A significant group/time interaction emerged for fatigue
      levels (P= .005). We found no significant group/time interaction for pain levels
      or function. CONCLUSIONS: Undertaking 15 minutes of moderate-intensity aerobic
      cycling exercise had no significant adverse effects on pain or function in people
      with MS and CFS (with a Karnofsky score of 50-80) within a 24-hour time period.
      These initial results suggest that people with MS or CFS may undertake 15 minutes
      of cycling as moderate aerobic exercise with no expected negative impact on pain
      or function.

PMID- 25061432
TI  - Value, challenges, and satisfaction of certification for multiple sclerosis
      specialists.
AB  - BACKGROUND: Specialist certification among interdisciplinary multiple sclerosis
      (MS) team members provides formal recognition of a specialized body of knowledge
      felt to be necessary to provide optimal care to individuals and families living
      with MS. Multiple sclerosis specialist certification (MS Certified Specialist, or
      MSCS) first became available in 2004 for MS interdisciplinary team members, but
      prior to the present study had not been evaluated for its perceived value,
      challenges, and satisfaction. METHODS: A sample consisting of 67 currently
      certified MS specialists and 20 lapsed-certification MS specialists completed the
      following instruments: Perceived Value of Certification Tool (PVCT), Perceived
      Challenges and Barriers to Certification Scale (PCBCS), Overall Satisfaction with
      Certification Scale, and a demographic data form. RESULTS: Satisfactory
      reliability was shown for the total scale and four factored subscales of the PVCT
      and for two of the three factored PCBCS subscales. Currently certified MS
      specialists perceived significantly greater value and satisfaction than lapsed
      certification MS specialists in terms of employer and peer recognition,
      validation of MS knowledge, and empowering MS patients. Lapsed-certification MS
      specialists reported increased confidence and caring for MS patients using
      evidence-based practice. Both currently certified and lapsed-certification groups
      reported dissatisfaction with MSCS recognition and pay/salary rewards.
      CONCLUSIONS: The results of this study can be used in efforts to encourage
      initial certification and recertification of interdisciplinary MS team members.

PMID- 25061433
TI  - Multiple sclerosis symptom recrudescence at the end of the natalizumab dosing
      cycle.
AB  - BACKGROUND: This study was undertaken to determine how frequently patients
      receiving natalizumab for multiple sclerosis (MS) experience recrudescence of
      their MS symptoms at the end of the dosing cycle. METHODS: One hundred
      consecutive MS patients receiving natalizumab completed a survey evaluating
      changes in symptoms during the natalizumab dosing cycle. Ninety-one patients also
      completed questionnaires at two time points: the first week after natalizumab
      infusion and the last week of the dosing cycle. These included the Multiple
      Sclerosis Quality of Life-54 (MSQOL-54), Fatigue Visual Analog Scale (VAS),
      Fatigue Severity Scale (FSS), and Beck Depression Inventory-II (BDI-II). RESULTS:
      End of dosing interval (EDI) symptoms were reported as currently being
      experienced by 57% of respondents. An additional 10% reported that they
      previously experienced that phenomenon, but not currently, and 33% reported never
      experiencing this. In those with EDI symptoms, they began to occur a median of 21
      days after infusion and improved again a median of 1 day after infusion. The most
      common symptoms reported were fatigue, weakness, walking impairment, and
      cognitive difficulties. No specific demographic or disease characteristics were
      associated with this phenomenon. In the subgroup with EDI symptoms, the MSQOL-54,
      Fatigue VAS, FSS, and BDI-II scores were all significantly worse in the last week
      of the dosing cycle when compared with the first week. No difference was seen in
      these scores between first and last week in the subgroup not experiencing symptom
      recrudescence. CONCLUSIONS: Recrudescence of fatigue, weakness, walking
      impairment, or cognitive difficulties at the end of the dosing cycle occurs in
      about two-thirds of MS patients receiving natalizumab.

PMID- 25061434
TI  - Rehabilitation interventions for the management of multiple sclerosis relapse: a
      short scoping review.
AB  - BACKGROUND: This review was undertaken to identify and summarize the existing
      evidence regarding postrelapse rehabilitation interventions in people with
      multiple sclerosis (MS). METHODS: Literature searches were conducted within the
      following databases: CINAHL Plus with Full Text, MEDLINE via Ovid, and PsycINFO
      via CSA Illumina. The following terms were searched as subject headings or
      keywords: choice behavior, counseling, decision making, disease management,
      health education, health promotion, patient education, patient participation,
      patient satisfaction, psychotherapy, rehabilitation, self-care, self-management.
      Then these searches were combined with the subject headings for relapsing
      remitting multiple sclerosis and subject heading or keywords for
      recurrence/relapse. Through the initial database search and additional citation
      search, 260 potentially relevant citations were identified. After screening the
      titles and abstracts as well as the citation search results, the reviewers agreed
      to keep five studies for the full-text reviews. Three rehabilitation intervention
      studies were included in the final review. RESULTS: A combined total of 145
      adults who experienced a relapse within the previous 5 months received 3 to 18
      days of rehabilitation. All three studies suggested the benefit of
      multidisciplinary rehabilitation for individuals with MS to improve impairment or
      disability. CONCLUSIONS: The three multidisciplinary rehabilitation interventions
      included in this review appear to be effective in improving impairment or
      disability of people with MS who experienced a relapse. Given the limited number
      of studies and their methodological limitations, the results must be interpreted
      cautiously. Further investigation is needed to better understand the
      rehabilitation needs of people with MS after relapse in order to improve research
      and care.

PMID- 25061435
TI  - Validation of mood measures for people with multiple sclerosis.
AB  - BACKGROUND: Valid assessments are needed in order to identify anxiety and
      depression in people with multiple sclerosis (MS). The objective of this study
      was to assess the validity of questionnaire measures of mood in people with MS.
      METHODS: People with MS were recruited from a clinic database and asked to
      complete and return a questionnaire containing the Beck Anxiety Inventory (BAI),
      Beck Depression Inventory-II (BDI-II), and Hospital Anxiety and Depression Scale
      (HADS). Those who returned the questionnaire were invited to complete a
      structured clinical interview, which was blind to the results of the
      questionnaire. RESULTS: The BDI-II and HADS were both found to be valid measures
      to detect depression and anxiety in people with MS. An optimum cutoff score of 23
      for the BDI-II yielded high sensitivity (85%) and high specificity (76%). An
      optimum cutoff score of 11 for the HADS demonstrated high sensitivity and
      specificity for both the Anxiety subscale (sensitivity 90%, specificity 92%) and
      the Depression subscale (sensitivity 77%, specificity 81%). The BAI had high
      sensitivity (80%) but poor specificity (46%) for detecting anxiety. CONCLUSION:
      The BDI-II and HADS can be used to identify mood disorders in people with MS.

PMID- 25061436
TI  - Letter to the editor.

PMID- 25061437
TI  - Editorial.

PMID- 25061438
TI  - Food Safety Knowledge, Beliefs and Behavior of Persons with AIDS: A Multicenter
      Study.
AB  - Persons living with AIDS are highly vulnerable to foodborne enteric infections
      including recurrent Salmonella septicemia and toxoplasmosis of the brain with the
      potential for substantial morbidity and mortality. Patients with immunologic AIDS
      in Chicago, New Orleans, and Bayamon were interviewed to determine gaps in food
      safety knowledge and prevalence of related behaviors in order to create targeted
      educational material for this population. A food safety score was calculated
      based on responses to 40 knowledge, belief, and behavior questions. Among 268
      AIDS patients interviewed, the overall food safety score was 63% (range 28% to
      93%). Many patients believed it was okay to eat higher risk food (38% for eating
      eggs served loose or runny, 27% for eating store-bought hot dogs without heating
      them first), 40% did not know that eating unpasteurized cheese may get germs
      inside their body that could cause hospitalization and possibly death, and 40%
      would not throw away salad that had been splashed with a few drops of raw chicken
      juice. These data demonstrate substantial knowledge gaps and behavioral risk
      related to acquisition of foodborne disease among AIDS patients. Healthcare
      providers should incorporate education regarding foodborne disease risk into
      routine outpatient discussion of improving and maintaining their health.

PMID- 25061440
TI  - Oxygen Pathways and Allostery in Monomeric Sarcosine Oxidase via Single-Sweep
      Free-Energy Reconstruction.
AB  - Monomeric sarcosine oxidase (MSOX) is a flavoprotein D-amino acid oxidase with
      reported sarcosine and oxygen activation sites on the re and si faces of the
      flavin ring, respectively. O2 transport routes to the catalytic interior are not
      well understood and are difficult to ascertain solely from MSOX crystal
      structures. A composite free-energy method known as single-sweep is used to map
      and thermodynamically characterize oxygen sites and routes leading to the
      catalytically active Lys265 from the protein surface. The result is a network of
      pathways and free energies within MSOX illustrating that oxygen can access two
      free-energy minima on the re face of the reduced flavin from four separate
      solvent portals. No such minimum is observed on the si face. The pathways are
      geometrically similar for three major states of the enzyme: (1) apo with a closed
      flavin cleft, (2) apo with an open flavin cleft, and (3) inhibitor-bound with a
      closed flavin cleft. Interestingly, free energies along these transport pathways
      display significantly deeper minima when the substrate-mimicking inhibitor 2
      furoic acid is bound at the sarcosine site, even at locations far from this site.
      This suggests a substrate-dependent allosteric modulation of the kinetics of O2
      transport from the solvent to the active site.

PMID- 25061439
TI  - Deregulation of the IL-1beta axis in chronic recurrent multifocal osteomyelitis.
AB  - BACKGROUND: This study aims to investigate the inflammasome response in
      peripheral blood mononuclear cells (PBMCs) and the expression of inflammasome
      components in bone biopsies from patients with chronic recurrent multifocal
      osteomyelitis (CRMO). METHODS: The expression of inflammasome components mRNAs
      was evaluated in PBMCs isolated from 15 CRMO patients and 13 healthy controls by
      quantitative real-time PCR. The Interleukin (IL)-1beta released in the medium of
      PBMC cultures after treatment with lipopolysaccharides (LPS) alone or LPS and ATP
      was measured by ELISA. Immunohistochemical staining for Apoptosis-associated
      Speck-like protein (ASC), caspase-1 (CASP-1), Nod-like receptor protein-3 (NLRP3)
      and IL-1beta expression was performed in bone biopsies from CRMO patients.
      RESULTS: mRNA levels of ASC, CASP-1 and IL-1beta were significantly higher in
      freshly isolated PBMCs from CRMO patients in active disease than in healthy
      controls. CASP-1 and IL-1beta transcript levels were significantly higher also in
      PBMCs from CRMO patients in remission compared to healthy controls. PBMCs from
      CRMO patients in active disease stimulated in vitro with LPS showed a significant
      increase in IL-1beta release compared to healthy control cells.
      Immunohistochemistry staining of bone tissue revealed the expression of
      inflammasome components in CRMO osteoclasts. CONCLUSIONS: Our data suggest that
      an abnormal regulation of IL-1beta axis may be involved in CRMO pathogenesis.

PMID- 25061441
TI  - Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free
      Energy Calculation.
AB  - Accelerated molecular dynamics (aMD) simulations greatly improve the efficiency
      of conventional molecular dynamics (cMD) for sampling biomolecular conformations,
      but they require proper reweighting for free energy calculation. In this work, we
      systematically compare the accuracy of different reweighting algorithms including
      the exponential average, Maclaurin series, and cumulant expansion on three model
      systems: alanine dipeptide, chignolin, and Trp-cage. Exponential average
      reweighting can recover the original free energy profiles easily only when the
      distribution of the boost potential is narrow (e.g., the range <=20kBT) as found
      in dihedral-boost aMD simulation of alanine dipeptide. In dual-boost aMD
      simulations of the studied systems, exponential average generally leads to high
      energetic fluctuations, largely due to the fact that the Boltzmann reweighting
      factors are dominated by a very few high boost potential frames. In comparison,
      reweighting based on Maclaurin series expansion (equivalent to cumulant expansion
      on the first order) greatly suppresses the energetic noise but often gives
      incorrect energy minimum positions and significant errors at the energy barriers
      (~2-3kBT). Finally, reweighting using cumulant expansion to the second order is
      able to recover the most accurate free energy profiles within statistical errors
      of ~kBT, particularly when the distribution of the boost potential exhibits low
      anharmonicity (i.e., near-Gaussian distribution), and should be of wide
      applicability. A toolkit of Python scripts for aMD reweighting "PyReweighting" is
      distributed free of charge at http://mccammon.ucsd.edu/computing/amdReweighting/.

PMID- 25061442
TI  - Multiscale Reactive Molecular Dynamics for Absolute pKa Predictions and Amino
      Acid Deprotonation.
AB  - Accurately calculating a weak acid's pKa from simulations remains a challenging
      task. We report a multiscale theoretical approach to calculate the free energy
      profile for acid ionization, resulting in accurate absolute pKa values in
      addition to insights into the underlying mechanism. Importantly, our approach
      minimizes empiricism by mapping electronic structure data (QM/MM forces) into a
      reactive molecular dynamics model capable of extensive sampling. Consequently,
      the bulk property of interest (the absolute pKa) is the natural consequence of
      the model, not a parameter used to fit it. This approach is applied to create
      reactive models of aspartic and glutamic acids. We show that these models predict
      the correct pKa values and provide ample statistics to probe the molecular
      mechanism of dissociation. This analysis shows changes in the solvation structure
      and Zundel-dominated transitions between the protonated acid, contact ion pair,
      and bulk solvated excess proton.

PMID- 25061443
TI  - Constant pH Molecular Dynamics in Explicit Solvent with Enveloping Distribution
      Sampling and Hamiltonian Exchange.
AB  - We present a new computational approach for constant pH simulations in explicit
      solvent based on the combination of the enveloping distribution sampling (EDS)
      and Hamiltonian replica exchange (HREX) methods. Unlike constant pH methods based
      on variable and continuous charge models, our method is based on discrete
      protonation states. EDS generates a hybrid Hamiltonian of different protonation
      states. A smoothness parameter s is used to control the heights of energy
      barriers of the hybrid-state energy landscape. A small s value facilitates state
      transitions by lowering energy barriers. Replica exchange between EDS potentials
      with different s values allows us to readily obtain a thermodynamically accurate
      ensemble of multiple protonation states with frequent state transitions. The
      analysis is performed with an ensemble obtained from an EDS Hamiltonian without
      smoothing, s = infinity, which strictly follows the minimum energy surface of the
      end states. The accuracy and efficiency of this method is tested on aspartic
      acid, lysine, and glutamic acid, which have two protonation states, a histidine
      with three states, a four-residue peptide with four states, and snake cardiotoxin
      with eight states. The pKa values estimated with the EDS-HREX method agree well
      with the experimental pKa values. The mean absolute errors of small benchmark
      systems range from 0.03 to 0.17 pKa units, and those of three titratable groups
      of snake cardiotoxin range from 0.2 to 1.6 pKa units. This study demonstrates
      that EDS-HREX is a potent theoretical framework, which gives the correct
      description of multiple protonation states and good calculated pKa values.

PMID- 25061444
TI  - Relative Binding Enthalpies from Molecular Dynamics Simulations Using a Direct
      Method.
AB  - The potential for reliably predicting relative binding enthalpies, DeltaDeltaE,
      from a direct method utilizing molecular dynamics is examined for a system of
      three phosphotyrosyl peptides binding to a protein receptor, the Src SH2 domain.
      The binding enthalpies were calculated from the potential energy differences
      between the bound and the unbound end-states of each peptide from equilibrium
      simulations in explicit water. The statistical uncertainties in the ensemble-mean
      energy values from multiple, independent simulations were obtained using a
      bootstrap method. Simulations were initiated with different starting coordinates
      as well as different velocities. Statistical uncertainties in DeltaDeltaE are 2
      to 3 kcal/mol based on calculations from 40, 10 ns trajectories for each system
      (three SH2-peptide complexes or unbound peptides). Uncertainties in relative
      component energies, comprising solute-solute, solute-solvent and solvent-solvent
      interactions, are considerably larger. Energy values were estimated from an
      unweighted ensemble averaging of multiple trajectories with the a priori
      assumption that all trajectories are equally likely. Distributions in energy-rmsd
      space indicate that the trajectories sample the same basin and the difference in
      mean energy values between trajectories is due to sampling of alternative local
      regions of this superbasin. The direct estimate of relative binding enthalpies is
      concluded to be a reasonable approach for well-ordered systems with DeltaDeltaE
      values greater than ~3 kcal/mol, although the approach would benefit from future
      work to determine properly distributed starting points that would enable
      efficient sampling of conformational space using multiple trajectories.

PMID- 25061445
TI  - Evaluation of CM5 Charges for Condensed-Phase Modeling.
AB  - The recently developed Charge Model 5 (CM5) is tested for its utility in
      condensed-phase simulations. The CM5 approach, which derives partial atomic
      charges from Hirshfeld population analyses, provides excellent results for gas
      phase dipole moments and is applicable to all elements of the periodic table.
      Herein, the adequacy of scaled CM5 charges for use in modeling aqueous solutions
      has been evaluated by computing free energies of hydration (DeltaGhyd) for 42
      neutral organic molecules via Monte Carlo statistical mechanics. An optimal
      scaling factor for the CM5 charges was determined to be 1.27, resulting in a mean
      unsigned error (MUE) of 1.1 kcal/mol for the free energies of hydration. Testing
      for an additional 20 molecules gave an MUE of 1.3 kcal/mol. The high precision of
      the results is confirmed by free energy calculations using both sequential
      perturbations and complete molecular annihilation. Performance for specific
      functional groups is discussed; sulfur-containing molecules yield the largest
      errors. In addition, the scaling factor of 1.27 is shown to be appropriate for
      CM5 charges derived from a variety of density functional methods and basis sets.
      Though the average errors from the 1.27*CM5 results are only slightly lower than
      those using 1.14*CM1A charges, the broader applicability and easier access to CM5
      charges via the Gaussian program are additional attractive features. The 1.27*CM5
      charge model can be used for an enormous variety of applications in conjunction
      with many fixed-charge force fields and molecular modeling programs.

PMID- 25061446
TI  - Further Development of the FFT-based Method for Atomistic Modeling of Protein
      Folding and Binding under Crowding: Optimization of Accuracy and Speed.
AB  - Recently, we (Qin, S.; Zhou, H. X. J. Chem. Theory Comput.2013, 9, 4633-4643)
      developed the FFT-based method for Modeling Atomistic Proteins-crowder
      interactions, henceforth FMAP. Given its potential wide use for calculating
      effects of crowding on protein folding and binding free energies, here we aimed
      to optimize the accuracy and speed of FMAP. FMAP is based on expressing protein
      crowder interactions as correlation functions and evaluating the latter via fast
      Fourier transform (FFT). The numerical accuracy of FFT improves as the grid
      spacing for discretizing space is reduced, but at increasing computational cost.
      We sought to speed up FMAP calculations by using a relatively coarse grid spacing
      of 0.6 A and then correcting for discretization errors. This strategy was tested
      for different types of interactions (hard-core repulsion, nonpolar attraction,
      and electrostatic interaction) and over a wide range of protein-crowder systems.
      We were able to correct for the numerical errors on hard-core repulsion and
      nonpolar attraction by an 8% inflation of atomic hard-core radii and on
      electrostatic interaction by a 5% inflation of the magnitudes of protein atomic
      charges. The corrected results have higher accuracy and enjoy a speedup of more
      than 100-fold over those obtained using a fine grid spacing of 0.15 A. With this
      optimization of accuracy and speed, FMAP may become a practical tool for
      realistic modeling of protein folding and binding in cell-like environments.

PMID- 25061448
TI  - ANALYSIS OF THE NEW REGULATORY BIOETHICAL REVIEW FRAMEWORK FOR CLINICAL TRIALS IN
      TURKEY.
AB  - We conducted a descriptive study of the existing research ethics committee (REC)
      review structure in Turkey with respect to clinical trials and discuss what can
      be expected in the future under the new regulation that came into effect in April
      2013. We identified 78 RECs in Turkey under the Ministry of Health (MOH) as of
      September 2012, categorised under geographic location, type and institution. We
      identified REC member lists from the MOH in the same month and further
      characterize them under: membership number, gender, and speciality. MOH,
      universities, national nongovernmental organizations such as the Turkish Medical
      Association and the Turkish Bioethics Association, as well as clinical research
      and pharmaceutical bodies are intensively interested in the enhancement of the
      current system of research ethics review in the country. The European Union and
      Council directives have been important sources that have guided new developments.
      Proper evaluation of the existing system and introduction of new regulatory
      framework are expected to further clarify the obstacles and offer opportunities
      for institutions, researchers, REC members and administrators.

PMID- 25061447
TI  - Thermodynamics of Deca-alanine Folding in Water.
AB  - The determination of the folding dynamics of polypeptides and proteins is
      critical in characterizing their functions in biological systems. Numerous
      computational models and methods have been developed for studying structure
      formation at the atomic level. Due to its small size and simple structure, deca
      alanine is used as a model system in molecular dynamics (MD) simulations. The
      free energy of unfolding in vacuum has been studied extensively using the end-to
      end distance of the peptide as the reaction coordinate. However, few studies have
      been conducted in the presence of explicit solvent. Previous results show a
      significant decrease in the free energy of extended conformations in water, but
      the alpha-helical state is still notably favored over the extended state.
      Although sufficient in vacuum, we show that end-to-end distance is incapable of
      capturing the full complexity of deca-alanine folding in water. Using alpha
      helical content as a second reaction coordinate, we deduce a more descriptive
      free-energy landscape, one which reveals a second energy minimum in the extended
      conformations that is of comparable free energy to the alpha-helical state.
      Equilibrium simulations demonstrate the relative stability of the extended and
      alpha-helical states in water as well as the transition between the two states.
      This work reveals both the necessity and challenge of determining a proper
      reaction coordinate to fully characterize a given process.

PMID- 25061449
TI  - Identification of Posttranslational Modifications in Peroxisome Proliferator
      Activated Receptor gamma Using Mass Spectrometry.
AB  - Posttranslational modification (PTM) of proteins is critical for various cellular
      processes. However, there are few studies examining PTMs in specific proteins
      using unbiased approaches. Here we report the attempt to identify the PTMs in
      peroxisome proliferator-activated receptor gamma (PPARgamma) proteins using our
      previously established PTM analysis system. In this study, we identified several
      PTMs in exogenously expressed PPARgamma2 proteins from 293T cells as well as
      endogenous PPARgamma1 proteins from a Caco-2 colon cancer cell line. The
      identified PTMs include phosphorylation of serine 112 and serine 81 in PPARgamma2
      and PPARgamma1, respectively, both of which are well-known mitogen-activated
      protein kinase- (MAP kinase-) mediated PTMs in PPARgamma proteins, thus
      confirming our experimental approach. Furthermore, previously unknown PTMs were
      also identified, demonstrating that this method can be applied to find previously
      unidentified PTMs in PPARgamma proteins and other proteins including nuclear
      receptors. 

PMID- 25061450
TI  - Percutaneous elimination of the left atrial appendage in quest for effective and
      safe prevention of stroke in patients with atrial fibrillation.

PMID- 25061451
TI  - Renal denervation after the symplicity HTN-3 trial.

PMID- 25061452
TI  - Is it worth closing the atrial septal defect in patients with insignificant
      shunt?
AB  - INTRODUCTION: Closure of the atrial septal defect in patients with insignificant
      shunt is controversial. AIM: To evaluate the outcomes of transcatheter closure of
      atrial septal defect (ASD) in symptomatic patients with borderline shunt.
      MATERIAL AND METHODS: One hundred and sixty patients (120 female, 40 male) with a
      mean age of 30.1 +/-16.2 (20-52) years with a small ASD who underwent
      transcatheter closure were analyzed. All patients had a small ASD with Qp: Qs
      ratio <= 1.5, mean 1.2 +/-0.9 (1.1-1.5) in echo examination. Cardiopulmonary
      exercise tests, clinical study, transthoracic echocardiographic study as well as
      quality of life (QoL) (measured using the SF36 questionnaire (SF36q)) were
      repeated in all patients before and after the procedure. RESULTS: The devices
      were successfully implanted in all patients. After 12 months of ASD closure, all
      the patients showed a significant improvement of exercise capacity (oxygen
      consumption - 21.9 +/-3.1 vs. 30.4 +/-7.7, p > 0.001). The QoL improved in 7
      parameters at 12-month follow-up. The mean SF36q scale increased significantly in
      141 (88.1%) patients of mean 43.2 +/-20.1 (7-69). A significant decrease of the
      right ventricular area (20.3 +/-1.3 cm(2) vs. 18.3 +/-1.2 cm(2), p < 0.001) and
      the right atrial area (15.2 +/-1.9 cm(2) vs. 12.0 +/-1.6 cm(2), p < 0.001) was
      observed at 12-month follow-up. CONCLUSIONS: Closure of ASD in the patients with
      insignificant shunt resulted in significant durable clinical and hemodynamic
      improvement after percutaneous treatment.

PMID- 25061453
TI  - Early outcomes of transcatheter aortic valve replacement in patients with severe
      aortic stenosis: single center experience.
AB  - INTRODUCTION: Transcatheter aortic valve implantation is a promising alternative
      to high risk surgical aortic valve replacement. The procedure is mainly indicated
      in patients with severe symptomatic aortic stenosis who cannot undergo surgery or
      who are at very high surgical risk. AIM: Description early results of our single
      center experience with balloon expandable aortic valve implantation. MATERIAL AND
      METHODS: Between July 2011 and August 2012, we screened in total 75 consecutive
      patients with severe aortic stenosis and high risk for surgery. Twenty-one of
      them were found ineligible for transcatheter aortic valve implantation (TAVI)
      because of various reasons, and finally we treated a total of 54 patients with
      symptomatic severe aortic stenosis (AS) who could not be treated by open heart
      surgery (inoperable) because of high-risk criteria. The average age of the
      patients was 77.4 +/-7.1; 27.8% were male and 72.2% were female. The number of
      patients in NYHA class II was 7 while the number of patients in class III and
      class IV was 47. RESULTS: The average mortality score of patients according to
      the STS scoring system was 8.5%. Pre-implantation mean and maximal aortic valve
      gradients were measured as 53.2 +/-14.1 mm Hg and 85.5 +/-18.9 mm Hg,
      respectively. Post-implantation mean and maximal aortic valve gradients were 9.0
      +/-3.0 and 18.2 +/-5.6, respectively (p < 0.0001). The left ventricular ejection
      fraction was calculated as 54.7 +/-14.4% before the operation and 58.0 +/-11.1%
      after the operation (p < 0.0001). The duration of discharge after the operation
      was 5.29 days, and a statistically significant correlation between the duration
      of discharge after the operation and STS was found (r = 0385, p = 0.004).
      CONCLUSIONS: We consider that with decreasing cost and increasing treatment
      experience, TAVI will be used more frequently in broader indications. Our
      experience with TAVI using the Edwards-Sapien XT (Edwards Lifesciences, Irvine,
      CA) devices suggests that this is an effective and relatively safe procedure for
      the treatment of severe aortic stenosis in suitable patients.

PMID- 25061454
TI  - A novel predictor of infarct-related artery patency before percutaneous
      intervention and in-hospital outcomes for ST-segment elevation myocardial
      infarction patients: serum bilirubin level.
AB  - INTRODUCTION: Previous studies have reported a relationship between serum
      bilirubin levels and coronary artery disease (CAD). However, data are rare up to
      now regarding the relation of bilirubin levels with infarct-related artery (IRA)
      patency in the setting of ST-segment elevation myocardial infarction (STEMI).
      Moreover, previous studies reported that increased bilirubin was related to
      impaired post-intervention coronary flow. To our knowledge, the association
      between serum total bilirubin (TB) levels and pre-primary percutaneous coronary
      intervention (PCI) with patency of IRA flow in STEMI patients has not been
      investigated. AIM: To evaluate the association of TB with pre-primary PCI,
      coronary flow and in-hospital major adverse cardiac events (MACE) in patients
      with STEMI. MATERIAL AND METHODS: A total of 360 consecutive patients with STEMI
      (mean age = 61.4 +/-13.7 years) admitted within 12 h from the time of symptom
      onset were enrolled. Patients were divided into 2 groups based on the serum TB
      levels. We defined normal flow as pre-PCI TIMI 3 flow, while impaired flow was
      defined as pre-PCI TIMI <= 2 flow. RESULTS: Pre-PCI impaired flow was higher in
      the TB group than pre-PCI normal flow (p < 0.001). In-hospital mortality and MACE
      were significantly higher in the high TB group (p = 0.002, p < 0.001
      respectively). In the receiver operating characteristic curve analysis, TB >
      0.825 mg/dl predicted impaired IRA flow before p-PCI with a sensitivity of 79%
      and specificity of 71%. CONCLUSIONS: The TB is an inexpensive and readily
      available marker for STEMI patients undergoing PCI. It can be used for risk
      stratification in this patient population.

PMID- 25061455
TI  - Comparison of inflammatory markers in non-dipper hypertension vs. dipper
      hypertension and in normotensive individuals: uric acid, C-reactive protein and
      red blood cell distribution width readings.
AB  - AIM: In this study, we investigated the relationship of increased inflammatory
      parameters (C-reactive protein - CRP), oxidative stress markers (serum uric acid 
      SUA) and red blood cell distribution width (RDW) with non-dipper hypertension
      (NDHT). MATERIAL AND METHODS: Among the individuals who presented to the
      cardiology clinic, 40 patients (32.5% male, 67.5% female; mean age: 54.4 +/-7.1)
      who had hypertension and were diagnosed with NDHT through ambulatory blood
      pressure monitoring, 40 age- and sex-matched dipper hypertension (DHT) patients
      (25% male, 75% female, mean age: 54.2 +/-7.0), and 40 normotensive individuals
      (42.5% male, 57.5% female, mean age: 51.9 +/-9.0) were enrolled in the study.
      Peripheral venous blood samples were collected from all the patients in order to
      evaluate the hematological and biochemical parameters. All the assessed
      parameters were compared among the groups. RESULTS: The CRP, RDW and uric acid
      levels were observed to be significantly higher in the non-dipper hypertension
      group in comparison to the dipper hypertension patients and the normotensive
      population (p < 0.05). These parameters were also significantly higher in the
      dipper HT group compared to the normotensive population (p < 0.05). CONCLUSIONS:
      We found in our study that increased CRP, uric acid and RDW levels, which are
      indicators of increased inflammation and oxidative stress, are significantly
      higher in the non-dipper HT patients in comparison to the dipper HT patients and
      control group.

PMID- 25061456
TI  - To uncover what is unknown or forgotten - cardiac magnetic resonance in the
      identification of vascular pathologies in patients after tetralogy of Fallot
      repair.
AB  - INTRODUCTION: In patients with repaired tetralogy of Fallot (TOF), various
      pathologies of the vascular system (both arterial and venous) may be present as a
      result of the previous therapeutic procedures or due to the congenital disease
      itself. Because of the limited diagnostic capabilities in the past, lacking
      surgical reports of patients operated on several decades ago and/or a long time
      since a corrective procedure, some of these pathologies/anomalies may remain
      unknown. AIM: To identify selected vascular pathologies with the use of cardiac
      magnetic resonance in patients after TOF repair. MATERIAL AND METHODS: We
      included 208 consecutive patients (median age 24.9 years, interquartile range
      20.5-36.7; 126 (60.6%) males) with repaired TOF undergoing cardiac magnetic
      resonance (CMR) imaging. RESULTS: Significant unexpected vascular
      pathologies/anomalies were found in 30 patients (14.4%) and included: uni- or
      bilateral occlusion of the subclavian artery (n = 20), persistent left superior
      vena cava (n = 7, in 1 case draining into the left atrium), occluded subclavian
      vein (n = 1), and interruption of the inferior vena cava (n = 2). Additionally, 1
      patient with the left subclavian artery occluded had an occlusion of the
      brachiocephalic vein. In none of the patients was the information about the
      uncovered pathology/anomaly present either in the referral information or in the
      present medical history. CONCLUSIONS: The CMR in patients with repaired TOF may
      uncover some pathologies/anomalies which were unknown or forgotten at the time of
      patients' referral for the study, and which may have a significant impact on
      patient management.

PMID- 25061457
TI  - Sudden cardiac arrest in takotsubo cardiomyopathy - a case study.
AB  - We present a 59-year-old woman who was admitted to hospital after sudden cardiac
      arrest due to ventricular fibrillation. Finally takotsubo syndrome was diagnosed.
      In the acute phase of takotsubo syndrome life-threatening ventricular arrhythmias
      and significant hemodynamic disorders may occur due to strong adrenergic
      stimulation and myocardial ischemia. It has been proved that the occurrence of
      torsade de pointes tachycardia in the acute phase of takotsubo cardiomyopathy is
      associated with QT prolongation. There are no clear guidelines on pharmacological
      treatment and implantable cardioverter defibrillator implantation after a past
      takotsubo episode. Takotsubo cardiomyopathy has not been entirely explained as an
      etiological disease. 

PMID- 25061458
TI  - Double stent loss during multivessel percutaneous coronary intervention in non-ST
      segment elevation acute coronary syndrome.
AB  - The following description presents a case of a 75-year-old female patient with
      non-ST-segment elevation acute coronary syndrome in whom there occurred an
      infrequent complication of percutaneous coronary angioplasty: uncontrolled
      intracoronary stent displacement from a balloon catheter. During the attempt to
      retrieve the device using the "small-balloon" technique, further slippage of the
      stent from the balloon catheter to the right deep femoral artery was observed.
      Therefore, it was decided to provide a commercial intravascular microloop,
      whereby the stent was successfully retrieved outside the vascular system. 

PMID- 25061459
TI  - Stroke caused by carotid artery dissection during ablation of atrial arrhythmia.
AB  - A 55-year-old woman was admitted to the Cardiology Department due to a poorly
      tolerated attack of tachyarrhythmia. The patient was enrolled in the
      electrophysiology study (EPS) study with radiofrequency ablation (RF). After a
      few applications, during transseptal puncture, the patient demonstrated a
      neurological syndrome in the form of progressive aphasia and weakness in the
      right extremities. Computed tomography angiography showed dissection of the left
      common carotid artery and internal carotid artery with a thrombus within their
      lumen. Intravenous thrombolytic therapy was initiated, which resulted in an
      improvement in the patient's neurological status. 

PMID- 25061460
TI  - Transcatheter closure of patent foramen ovale using the internal jugular venous
      approach.
AB  - Transcatheter closure of patent foramen ovale is routinely performed using the
      transfemoral approach, which is safe and technically easy. Our case represents
      the rare situation where the procedure needs to be performed using the right
      internal jugular venous approach. According to our best knowledge this is the
      first report of a patent foramen ovale closure procedure with access through the
      internal jugular with necessity to advance the guide wire and transseptal sheath
      into the left ventricle. Developing alternative techniques of transcatheter
      patent foramen ovale closure seems to be especially important in rare cases where
      transfemoral access is unavailable. 

PMID- 25061461
TI  - Chronic total occlusion successfully treated with a bioresorbable everolimus
      eluting vascular scaffold.
AB  - Fully bioresorbable vascular scaffolds (BVS) are a new approach to the
      percutaneous treatment of coronary artery disease. The BVS have not yet been
      fully tested in complex lesions, including chronic total occlusion (CTO). We
      report a CTO case successfully treated with a second-generation bioabsorbable
      drug-eluting scaffold. 

PMID- 25061462
TI  - Intervention on the left main coronary artery. Importance of periprocedural and
      follow-up intravascular ultrasonography guidance.
AB  - Periprocedural intravascular ultrasonography guidance for left main coronary
      artery stenting is well established. However, the role of this tool is also
      important at follow-up interventions. We present a case of a patient with
      previous history of left main coronary artery angioplasty. During a recent
      attempt to treat tight stenosis in the left anterior descending coronary artery,
      it was not possible to advance the stent into the left main coronary artery.
      Intravascular ultrasonography explained the difficulties encountered. 

PMID- 25061463
TI  - Collateral blood supply to common femoral artery from intercostal arteries.

PMID- 25061464
TI  - Myocardial ischemia induced by three-vessel coronary-cameral fistulas.
AB  - Coronary-cameral fistula is a scarce clinical entity, which is defined as an
      anomalous communication between any epicardial coronary artery and cardiac
      chambers or large vessels. We aimed to present a case of multiple coronary
      cameral fistulas causing myocardial ischemia. 

PMID- 25061465
TI  - Coronary spasm that caused non-ST elevation myocardial infarction appeared in
      cath lab due to vasovagal reaction.
AB  - Coronary artery spasm is sometimes an unrecognized cause of myocardial ischemia.
      Myocardial ischemia is not always a product of fixed stenosis; it can also be
      induced by dynamic, transient stenosis. The angiogram represents the current
      state of vasculature at the time of examination and absence of stenosis does not
      mean disease absence. We present a case of right coronary artery spasm that
      caused non-ST elevation myocardial infarction and arrhythmias and was induced
      again in the cath lab due to vasovagal reaction. 

PMID- 25061466
TI  - Functional assessment of a left coronary-pulmonary artery fistula by coronary
      flow reserve.
AB  - We report a 71-year-old man who presented with atypical chest pain. Coronary
      angiography did not reveal left main or proximal left anterior descending
      coronary artery stenosis, but a fistulous communication with a stronger tube-like
      fistula was present originating from the proximal left anterior descending
      coronary artery and emptying into the main pulmonary artery. Fractional flow
      reserve and coronary flow reserve measurements were performed to gain more data
      on the potential functional aspects of this fistula. With the present case, the
      importance of functional evaluation of these fistulas is demonstrated. 

PMID- 25061467
TI  - Uric Acid Puzzle: Dual Role as Anti-oxidantand Pro-oxidant.
AB  - Hyperuricemia is known to be associated with the presence of cardiovascular and
      metabolic syndrome and with the development of incipient kidney disease and an
      accelerated renal progression. However, an elevated uric acid level was not
      generally regarded as a true etiology or mediator, but an indicator of these
      diseases. Uric acid has recently regained the clinical interest and popularity
      based on emerging data suggesting the causative role of hyperuricemia in
      cardiovascular and renal disease. Experimental data demonstrates oxidative stress
      is one of the earliest phenomena observed in vascular, renal, liver cells and
      adipocytes exposed to uric acid. Since uric acid is one of the major antioxidants
      of plasma acting as a free radical scavenger and a chelator of transitional metal
      ion, uric acid-induced oxidative stress seems paradoxical. Data regarding the
      clinical implication of hyperuricemia is even more confusing, which defines
      hyperuricemia as a useless parameter to be eliminated from routine follow-up or a
      major risk factor to be therapeutic target. With a review of experimental and
      epidemiologic data, the presence of molecular switch to regulate the role of uric
      acid as anti- or pro-oxidant in different compartment of our body is suggested,
      which may shed light on understanding the paradoxical role of uric acid and
      solving the "uric acid debate". 

PMID- 25061468
TI  - Dietary salt intake and hypertension.
AB  - Over the past century, salt has been the subject of intense scientific research
      related to blood pressure elevation and cardiovascular mortalities. Moderate
      reduction of dietary salt intake is generally an effective measure to reduce
      blood pressure. However, recently some in the academic society and lay media
      dispute the benefits of salt restriction, pointing to inconsistent outcomes noted
      in some observational studies. A reduction in dietary salt from the current
      intake of 9-12 g/day to the recommended level of less than 5-6 g/day will have
      major beneficial effects on cardiovascular health along with major healthcare
      cost savings around the world. The World Health Organization (WHO) strongly
      recommended to reduce dietary salt intake as one of the top priority actions to
      tackle the global non-communicable disease crisis and has urged member nations to
      take action to reduce population wide dietary salt intake to decrease the number
      of deaths from hypertension, cardiovascular disease and stroke. However, some
      scientists still advocate the possibility of increased risk of CVD morbidity and
      mortality at extremes of low salt intake. Future research may inform the optimal
      sodium reduction strategies and intake targets for general populations. Until
      then, we have to continue to build consensus around the greatest benefits of salt
      reduction for CVD prevention, and dietary salt intake reduction strategies must
      remain at the top of the public health agenda. 

PMID- 25061469
TI  - Association between Hypophosphatemia and Cardiac Arrhythmias in the Early Stage
      of Sepsis: Could Phosphorus Replacement Treatment Reduce the Incidence of
      Arrhythmias?
AB  - It is well known that new-onset arrhythmias are common in septic patients. It is
      thought that hypophosphatemia in the early stages of sepsis may contribute to the
      development of new arrhythmias. In this study, we hypothesized that intravenous
      (IV) phosphorus replacement may reduce the incidence of arrhythmias in critically
      ill patients. 34 adult septic patients with hypophosphatemia admitted to the
      general intensive care unit were treated with IV phosphorus replacement per ICU
      protocol, and the incidence of new arrhythmias were compared with 16 patients
      from previously published data. IV phosphorus replacement was associated with a
      significantly reduced incidence of arrhythmias (38% vs. 63%, p=0.04). There were
      no differences in observed mortality between subgroups, which may be due to the
      small sample size. This study demonstrated that IV phosphorus replacement might
      be effective in reducing the incidence of new arrhythmias in septic patients. 

PMID- 25061470
TI  - A Case of Post-radiotherapy Urethral Stricture with Spontaneous Bladder Rupture,
      Mimicking Obstructive Uropathy due to Cancer Metastasis.
AB  - Non-traumatic, spontaneous urinary bladder rupture is a rare complication of
      urethral stricture. Furthermore, its symptoms are often nonspecific, and
      misdiagnosis is common. The authors experienced a case of urethral stricture with
      spontaneous bladder rupture and bilateral hydronephrosis, mimicking obstructive
      uropathy attributed to cancer metastasis. A 55-year-old woman was admitted with
      abdominal pain and distension, oliguria, and an elevated serum creatinine level.
      She had undergone radical hysterectomy for uterine cervical cancer and received
      post-operative concurrent chemoradiation therapy 13 years previously. Non
      contrast enhanced computed tomography showed massive ascites and bilateral
      hydronephrosis. The initial diagnosis was acute kidney injury due to obstructive
      uropathy caused by malignant disease. After improvement of her renal function by
      bilateral percutaneous nephrostomy catheterization, contrast-enhanced computed
      tomography and a cytologic examination of ascites showed no evidence of
      malignancy. However, during retrograde pyelography, a severe urethral stricture
      was found, and subsequent cystography showed leakage of contrast into the
      peritoneal cavity and cystoscopy revealed a defect of the posterior bladder wall.
      After urethral dilatation and primary closure of the bladder wall, acute kidney
      injury and ascites were resolved. 

PMID- 25061471
TI  - Inhibition of Human Cytochrome P450 Enzymes by Allergen Removed Rhus verniciflua
      Stoke Standardized Extract and Constituents.
AB  - Objective. Potential interactions between herbal extracts and the cytochrome P450
      (CYP) system lead to serious adverse events or decreased drug efficacy. Rhus
      verniciflua stoke (RVS) and its constituents have been reported to have various
      pharmacological properties. We evaluated the inhibitory potential of RVS and its
      constituents on the major CYP isoforms. Methods. The effects of allergen removed
      RVS (aRVS) standardized extract and major components, fustin and fisetin isolated
      from aRVS, were evaluated on CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4
      isoenzyme activity by a luminescent CYP recombinant human enzyme assay. Results.
      The aRVS extract showed relative potent inhibitory effects on the CYP2C9 (IC50,
      <0.001 MUg/mL), CYP2C19 (IC50, 9.68 MUg/mL), and CYP1A2 (IC50, 10.0 MUg/mL).
      However, it showed weak inhibition on CYP3A4 and CYP2D6. Fustin showed moderate
      inhibitory effects on the CYP2C19 (IC50, 64.3 MUg/mL) and weak inhibition of the
      other CYP isoforms similar to aRVS. Fisetin showed potent inhibitory effects on
      CYP2C9, CYP2C19, and CYP1A2. Fisetin showed moderate inhibition of CYP2D6 and
      weak inhibition of CYP3A4. Conclusions. These results indicate that aRVS, a
      clinically available herbal medicine, could contribute to herb-drug interactions
      when orally coadministered with drugs metabolized by CYP2C9, CYP2C19, and CYP1A2.

PMID- 25061472
TI  - Image segmentation and identification of paired antibodies in breast tissue.
AB  - Comparing staining patterns of paired antibodies designed towards a specific
      protein but toward different epitopes of the protein provides quality control
      over the binding and the antibodies' ability to identify the target protein
      correctly and exclusively. We present a method for automated quantification of
      immunostaining patterns for antibodies in breast tissue using the Human Protein
      Atlas database. In such tissue, dark brown dye 3,3'-diaminobenzidine is used as
      an antibody-specific stain whereas the blue dye hematoxylin is used as a
      counterstain. The proposed method is based on clustering and relative scaling of
      features following principal component analysis. Our method is able (1) to
      accurately segment and identify staining patterns and quantify the amount of
      staining and (2) to detect paired antibodies by correlating the segmentation
      results among different cases. Moreover, the method is simple, operating in a low
      dimensional feature space, and computationally efficient which makes it suitable
      for high-throughput processing of tissue microarrays. 

PMID- 25061473
TI  - Advanced medical image analysis.

PMID- 25061474
TI  - Enumerating all maximal frequent subtrees in collections of phylogenetic trees.
AB  - BACKGROUND: A common problem in phylogenetic analysis is to identify frequent
      patterns in a collection of phylogenetic trees. The goal is, roughly, to find a
      subset of the species (taxa) on which all or some significant subset of the trees
      agree. One popular method to do so is through maximum agreement subtrees (MASTs).
      MASTs are also used, among other things, as a metric for comparing phylogenetic
      trees, computing congruence indices and to identify horizontal gene transfer
      events. RESULTS: We give algorithms and experimental results for two approaches
      to identify common patterns in a collection of phylogenetic trees, one based on
      agreement subtrees, called maximal agreement subtrees, the other on frequent
      subtrees, called maximal frequent subtrees. These approaches can return subtrees
      on larger sets of taxa than MASTs, and can reveal new common phylogenetic
      relationships not present in either MASTs or the majority rule tree (a popular
      consensus method). Our current implementation is available on the web at
      https://code.google.com/p/mfst-miner/. CONCLUSIONS: Our computational results
      confirm that maximal agreement subtrees and all maximal frequent subtrees can
      reveal a more complete phylogenetic picture of the common patterns in collections
      of phylogenetic trees than maximum agreement subtrees; they are also often more
      resolved than the majority rule tree. Further, our experiments show that
      enumerating maximal frequent subtrees is considerably more practical than
      enumerating ordinary (not necessarily maximal) frequent subtrees.

PMID- 25061475
TI  - Comparative survey of go/no-go results to identify the inhibitory control ability
      change of Japanese children.
AB  - This research, conducted in 1998 and 2008, uses go/no-go data to investigate the
      fundamentals of cognitive functioning in the inhibitory control ability of
      Japanese children. 844 subjects from kindergarten to junior high school
      participated in go/no-go task experiments. Performance of go/no-go tasks, which
      are frequently used to investigate response inhibition, measures a variety of
      cognitive components besides response inhibition. With normal brain development,
      the ability to inhibit responses improves substantially in adolescence. An
      increase over time in the error rate during the go/no-go tasks of subjects of the
      same age indicates that these processes are not functioning properly. Comparisons
      between the 1998 and 2008 data revealed several differences in error rates. In
      2008, there were increases in the number of errors in groups from each age range.
      The comparison also revealed that overall error rates peaked at later ages in the
      2008 subjects. Taken together, these results show changing conditions in the
      inhibitory function of the prefrontal cortex. However, the reason for these
      changing conditions remains unclear. While a lifestyle questionnaire revealed
      several differences in factors such as bedtimes and hours spent watching TV,
      analysis did not reveal a significant correlation. 

PMID- 25061476
TI  - Modified method to improve the design of Petlyuk distillation columns.
AB  - BACKGROUND: A response surface analysis was performed to study the effect of the
      composition and feeding thermal conditions of ternary mixtures on the number of
      theoretical stages and the energy consumption of Petlyuk columns. A modification
      of the pre-design algorithm was necessary for this purpose. RESULTS: The modified
      algorithm provided feasible results in 100% of the studied cases, compared with
      only 8.89% for the current algorithm. The proposed algorithm allowed us to attain
      the desired separations, despite the type of mixture and the operating conditions
      in the feed stream, something that was not possible with the traditional pre
      design method. The results showed that the type of mixture had great influence on
      the number of stages and on energy consumption. A higher number of stages and a
      lower consumption of energy were attained with mixtures rich in the light
      component, while higher energy consumption occurred when the mixture was rich in
      the heavy component. CONCLUSIONS: The proposed strategy expands the search of an
      optimal design of Petlyuk columns within a feasible region, which allow us to
      find a feasible design that meets output specifications and low thermal loads.

PMID- 25061477
TI  - Different stability of social-communication problems and negative demanding
      behaviour from infancy to toddlerhood in a large Dutch population sample.
AB  - BACKGROUND: Little is known about the stability of behavioural and developmental
      problems as children develop from infants to toddlers in the general population.
      Therefore, we investigated behavioural profiles at two time points and determined
      whether behaviours are stable during early development. METHODS: Parents of 4,237
      children completed questionnaires with 62 items about externalizing,
      internalizing, and social-communicative behaviour when the children were 14-15
      and 36-37 months old. Factor mixture modelling identified five homogeneous
      profiles at both time points: three with relatively normal behaviour or with
      mild/moderate problems, one with clear communication and interaction problems,
      and another with pronounced negative and demanding behaviour. RESULTS: More than
      85% of infants with normal behaviour or mild problems at 14-15 months were
      reported to behave relatively typically as toddlers at 36-37 months. A similar
      percentage of infants with moderate communication problems outgrew their problems
      by the time they were toddlers. However, infants with severe problems had mild to
      severe problems as toddlers, and did not show completely normal behaviour.
      Improvement over time occurred more often in children with negative and demanding
      behaviour than in children with communication and interaction problems. The
      former showed less homotypic continuity than the latter. CONCLUSIONS: Negative
      and demanding behaviour is more often transient and a less specific predictor of
      problems in toddlerhood than communication and interaction problems.

PMID- 25061478
TI  - Health in older age: The German Ageing Survey (DEAS).

PMID- 25061479
TI  - A fibrin/hyaluronic acid hydrogel for the delivery of mesenchymal stem cells and
      potential for articular cartilage repair.
AB  - BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease affecting
      approximately 27 million Americans, and even more worldwide. OA is characterized
      by degeneration of subchondral bone and articular cartilage. In this study, a
      chondrogenic fibrin/hyaluronic acid (HA)-based hydrogel seeded with bone marrow
      derived mesenchymal stem cells (BMSCs) was investigated as a method of
      regenerating these tissues for OA therapy. This chondrogenic hydrogel system can
      be delivered in a minimally invasive manner through a small gauge needle, forming
      a three-dimensional (3D) network structure in situ. However, an ongoing problem
      with fibrin/HA-based biomaterials is poor mechanical strength. This was addressed
      by modifying HA with methacrylic anhydride (MA) (HA-MA), which reinforces the
      fibrin gel, thereby improving mechanical properties. In this study, a range of
      fibrinogen (the fibrin precursor) and HA-MA concentrations were explored to
      determine optimal conditions for increased mechanical strength, BMSC
      proliferation, and chondrogenesis potential in vitro. RESULTS: Increased
      mechanical strength was achieved by HA-MA reinforcement within fibrin hydrogels,
      and was directly correlated with increasing HA-MA concentration. Live/dead
      staining and metabolic assays confirmed that the crosslinked fibrin/HA-MA
      hydrogels provided a suitable 3D environment for BMSC proliferation. Quantitative
      polymerase chain reaction (qPCR) of BMSCs incubated in the fibrin/HA-MA hydrogel
      confirmed decreased expression of collagen type 1 alpha 1 mRNA with an increase
      in Sox9 mRNA expression especially in the presence of a platelet lysate,
      suggesting early chondrogenesis. CONCLUSION: Fibrin/HA-MA hydrogel may be a
      suitable delivery method for BMSCs, inducing BMSC differentiation into
      chondrocytes and potentially aiding in articular cartilage repair for OA therapy.

PMID- 25061482
TI  - Introduction to the Special Issue.

PMID- 25061480
TI  - Orquestic regulation of neurotransmitters on reward-seeking behavior.
AB  - The ventral tegmental area is strongly associated with the reward system.
      Dopamine is released in areas such as the nucleus accumbens and prefrontal cortex
      as a result of rewarding experiences such as food, sex, and neutral stimuli that
      become associated with them. Electrical stimulation of the ventral tegmental area
      or its output pathways can itself serve as a potent reward. Different drugs that
      increase dopamine levels are intrinsically rewarding. Although the dopaminergic
      system represent the cornerstone of the reward system, other neurotransmitters
      such as endogenous opioids, glutamate, gamma-Aminobutyric acid, acetylcholine,
      serotonin, adenosine, endocannabinoids, orexins, galanin and histamine all affect
      this mesolimbic dopaminergic system. Consequently, genetic variations of
      neurotransmission are thought influence reward processing that in turn may affect
      distinctive social behavior and susceptibility to addiction. Here, we discuss
      current evidence on the orquestic regulation of different neurotranmitters on
      reward-seeking behavior and its potential effect on drug addiction. 

PMID- 25061481
TI  - Genetics and genomics of Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressively debilitating neurodegenerative
      syndrome. Although best described as a movement disorder, the condition has
      prominent autonomic, cognitive, psychiatric, sensory and sleep components.
      Striatal dopaminergic innervation and nigral neurons are progressively lost, with
      associated Lewy pathology readily apparent on autopsy. Nevertheless, knowledge of
      the molecular events leading to this pathophysiology is limited. Current
      therapies offer symptomatic benefit but they fail to slow progression and
      patients continue to deteriorate. Recent discoveries in sporadic, Mendelian and
      more complex forms of parkinsonism provide novel insight into disease etiology;
      28 genes, including those encoding alpha-synuclein (SNCA), leucine-rich repeat
      kinase 2 (LRRK2) and microtubule-associated protein tau (MAPT), have been linked
      and/or associated with PD. A consensus regarding the affected biological pathways
      and molecular processes has also started to emerge. In early-onset and more a
      typical PD, deficits in mitophagy pathways and lysosomal function appear to be
      prominent. By contrast, in more typical late-onset PD, chronic, albeit subtle,
      dysfunction in synaptic transmission, early endosomal trafficking and receptor
      recycling, as well as chaperone-mediated autophagy, provide a unifying synthesis
      of the molecular pathways involved. Disease-modification (neuroprotection) is no
      longer such an elusive goal given the unparalleled opportunity for diagnosis,
      translational neuroscience and therapeutic development provided by genetic
      discovery. 

PMID- 25061483
TI  - Prospective validation of neonatal vancomycin dosing regimens is urgently needed.
AB  - BACKGROUND: Although vancomycin is frequently used to treat neonatal late-onset
      sepsis, there is no consensus on the optimal dosing regimen. Because many
      neonates needed dosing adaptation due to suboptimal trough values, the vancomycin
      dosing regimen in our neonatal department was changed during 2012. OBJECTIVE: We
      aimed to document the need for validation of neonatal vancomycin dosing by
      exploring serum trough levels achieved using 2 published dosing regimens
      (previous regimen: based on postmenstrual age and serum creatinine and new
      regimen: based on postmenstrual age and postnatal age) and to identify covariates
      associated with suboptimal vancomycin trough levels (<10 mg/L). METHODS: Routine
      therapeutic drug monitoring serum trough levels quantified after initiation of
      intravenous vancomycin therapy and clinical covariates were retrospectively
      collected. Median vancomycin trough levels of both dosing regimens were compared
      using the Mann-Whitney U test. The influence of continuous and dichotomous
      covariates on achieving a suboptimal trough level was explored using the Van
      Elteren test (stratified Mann-Whitney U test) and Mantel-Haenszel test
      (stratified chi(2) test), respectively. Covariates significant in monovariate
      analysis were subsequently included in a logistic regression analysis. RESULTS:
      In total, 294 observations (median current weight 1870 g [range = 420-4863 g] and
      median postmenstrual age 35.07 weeks [range = 25.14-56.00 weeks]) were included.
      Using the previous and new dosing regimens, 66.3% and 76.2% of trough levels,
      respectively, were below 10 mg/L. Overall, suboptimal vancomycin trough values
      were significantly associated with lower weight (birth weight and current weight)
      and age (gestational age and postmenstrual age). CONCLUSIONS: The majority of
      vancomycin trough levels in neonates achieved using 2 published dosing regimens
      did not reach the target of 10 mg/L. This illustrates the urgent need for
      prospective validation of neonatal vancomycin dosing regimens. We anticipate that
      dosing regimens integrating covariates reflecting general physiological
      maturation and renal maturation, as well as disease characteristics, could
      improve vancomycin exposure in neonates.

PMID- 25061484
TI  - Therapeutic and prophylactic management of bleeding from oesophageal and gastric
      varices - recommendations of the Working Group of the National Consultant for
      Gastroenterology.
AB  - Gastroesophageal varices are one of the most serious consequences of portal
      hypertension. One-third of patients with varices will develop variceal
      haemorrhage. Despite significant improvements in the outcomes of treatment,
      mortality due to bleeding from gastro-oesophageal varices still remains very
      high. These recommendations present optimal management of patients with non
      bleeding and bleeding varices. 

PMID- 25061485
TI  - The role of gastrointestinal hormones in the pathogenesis of obesity and type 2
      diabetes.
AB  - Obesity, influencing the increase of incidence of type 2 diabetes, cardiovascular
      complications and cancer is a growing medical problem worldwide. The feelings of
      hunger and satiety are stimulated by the "gut-brain axis", where a crucial role
      is played by gastrointestinal hormones: glucagon-like peptide 1, glucose
      dependent insulinotropic polypeptide, pancreatic polypeptide, peptide YY,
      oxyntomodulin, cholecystokinin and ghrelin. These hormones affect not only the
      functioning of the digestive tract, but also might have effects on insulin
      secretion and are mediators which affect brain areas involved in the regulation
      of food intake. The effect of their actions can be antagonistic as well as an
      additive or synergistic, and their secretion is dependent on many factors, such
      as dietary nutrients or the energy state of the body. Changes in circulating gut
      hormones concentrations result in activation of various pathways primarily within
      the hypothalamus and brain stem areas, which modulate feeding behaviour and a
      number of metabolic processes. 

PMID- 25061486
TI  - Procedural sedation and analgesia in children undergoing digestive endoscopic
      procedures - paediatrician or anaesthesiologist?
AB  - Endoscopic procedures of the gastrointestinal tract were successfully introduced
      into paediatric practice in the 1970s. Recent expansive development has become
      useful for improvement of both diagnosis and treatment in many children with
      gastrointestinal diseases. Most of these procedures are performed under
      procedural sedation (PSA) knowing anatomical, physiological and psychological
      differences and requiring good experience from the paediatrician and
      anaesthesiologist. These principles help to provide the procedure safely and
      minimise adverse events, which are greater the smaller the child is. Procedural
      sedation and analgesia in healthy children can be performed by a paediatrician,
      but children with congenital defects and serious coexisting diseases (ASA >= III)
      and also during the usage of anaesthetics (e.g. propofol), should be managed by
      an anaesthesiologist. 

PMID- 25061487
TI  - Osteoporosis in primary biliary cirrhosis of the liver.
AB  - Osteoporosis is a metabolic bone disease associated with a reduction in bone mass
      and deterioration of bone architecture, leading to increased fragility and
      subsequent low-trauma fractures in the vertebral column, hip, forearm and other
      bones. In literature, metabolic bone diseases such as osteoporosis and
      osteomalacia have been recognised as a complication of chronic liver disease,
      although the mechanisms of this association remain unclear. An increasing body of
      research data indicates a strong relationship between osteoporosis and primary
      biliary cirrhosis (PBC), which mainly results from early diagnosis of the
      disease, usually when it is still asymptomatic. The incidence of osteoporosis in
      PBC ranges from 20% to 44% and increases with the progression of the disease.
      Similarly, the incidence of bone fractures is high in this group of patients (10
      20%). In this article, current knowledge on risk factors, pathogenesis, diagnosis
      and treatment of osteoporosis in PBC is reviewed. 

PMID- 25061488
TI  - IRS-2 G1057D polymorphism in Turkish patients with colorectal cancer.
AB  - INTRODUCTION: Gene polymorphisms have a broad range of analysis, but are of
      particular use in molecular medicine due to their potential in revealing the
      genetic tendency in diseases such as cancer, heart attack etc. These studies
      basically depend on mutations that can be detected by proper techniques. The
      genes coding the insulin receptor substrate (IRS) proteins are among the most
      widely analysed polymorphisms in various cancer types, in which a G1057D mutation
      is seen. AIM: To determine the risk of colon cancer by analysing the IRS-2 gene
      polymorphism in Turkish patients. MATERIAL AND METHODS: A total of 161 newly
      diagnosed colorectal cancer patients were analysed and compared to 197 unrelated
      healthy controls. A polymerase chain reaction-based restriction fragment length
      polymorphism method was carried out. RESULTS: No differences were observed
      between the patient and control groups for both allele and genotype frequencies
      of the IRS-2 G1057D gene. CONCLUSIONS: Our results demonstrated that IRS-2 G1057D
      polymorphism is not associated with colorectal cancer in the Turkish population.
      This research is a preliminary and original study in Turkish patients with
      colorectal cancer. It also provides population-level genetic data on IRS-2 in the
      Turkish population. Further studies should be performed on larger number of
      patients and controls for more reliable results about the genetic tendency in
      colorectal cancer in Turkey. The study is a collaborative work of different
      universities and scientists.

PMID- 25061489
TI  - Health-related quality of life in patients with anal fissure: effect of type D
      personality.
AB  - INTRODUCTION: Health-related quality of life (HRQL) is a significant factor in
      describing the burden of illness and the impact of treatment in patients with
      gastrointestinal disease. Type D (distressed) personality is defined as the co
      occurrence of negative affect and social inhibition. AIM: To assess the
      prevalence of type D personality in patients with anal fissure and to investigate
      whether the presence of a type D personality would affect HRQL in patients with
      anal fissure. MATERIAL AND METHODS: One hundred outpatients with anal fissure
      with no psychiatric comorbidity were consecutively enrolled, along with 100
      healthy controls. Type D Scale (DS14) and General Health Survey Short Form-36 (SF
      36) were used in the collection of data. RESULTS: Patients with anal fissure
      scored lower on physical roles and bodily pain dimensions of SF-36 than healthy
      subjects (p < 0.05). Thirty-three patients with anal fissure (33%) and 16
      controls (16%) had scored above the cut-off score of the DS14 (p < 0.05).
      Patients with a type D personality were found to score lower on bodily pain and
      social roles domains of HRQL than patients without a type D personality.
      CONCLUSIONS: Type D personality was associated with increased perceived bodily
      pain and social roles in patients with anal fissure. Type D personality construct
      may be an important consideration when assessing HRQL outcomes. A
      multidimensional approach may be valuable in the assessment of patients
      presenting with anal fissure, because a subgroup with type-D personality might
      benefit from psychological therapies.

PMID- 25061490
TI  - A clinical psychologist's perspective of mental disorders in patients of 70 years
      of age or more, who underwent digestive tract cancer surgeries.
AB  - INTRODUCTION: Behavioural and psychological disorders in surgical patients
      treated for malignant diseases are not always adequately appreciated and often
      neglected. However, they are very important in the therapeutic process because
      they may severely disturb physical and psychological rehabilitation, the
      patient's effective struggle with malignancy, environmental relationships and
      quality of life. Professional preoperative psychological assessment is necessary
      to facilitate therapy for malignant diseases in those patients who are
      specifically exposed to a severely stressful situation. AIM: To investigate the
      incidence of depression, hallucinations and anxiety in patients undergoing
      surgery for malignancy of the digestive tract. The influence of those disorders
      on the period of hospitalisation, cooperation with medical staff and
      postoperative quality of life was analysed. MATERIAL AND METHODS: A routine
      program of psychological and psychiatric care for patients with malignancy, who
      undergo extensive surgical procedures, was implemented in our department several
      years ago. The program allows for identification of patients with a high risk of
      psychiatric disorders to provide them with special psychological support. Sixty
      nine patients with advanced malignancy were followed after the surgery between
      2009 and 2010. All were examined by a professional psychologist. A QLQ C-30
      (EORTC) questionnaire was used to assess the quality of life. RESULTS: Psychotic
      disorders were present in 53.6% of examined patients. Depression was dominating
      (57%), followed by anxiety (28%) and hallucinations (15%). The mean hospital stay
      was different between those, respectively, with and without psychotic disorders
      (17 days vs. 15 days). Quality of life index for patients at risk was 3.8 vs. 5.1
      for more psychologically stable patients. CONCLUSIONS: Approximately 50% of
      patients undergoing surgery for malignant diseases develop severe psychotic
      disorders in the postoperative period. Preoperative psychological assessment
      seems to be extremely useful in providing adequate postoperative psychological
      support for individual patients.

PMID- 25061491
TI  - Preoperative glucose abnormalities in patients with pancreatic tumours.
AB  - INTRODUCTION: Pancreatic cancer is a neoplasm characterised by poor prognosis.
      The only effective, possible treatment is radical surgery, but most patients do
      not qualify for surgery because of delayed diagnosis. AIM: To determine if
      assessment of endocrine pancreatic function could serve as a means of screening
      for pancreatic cancer. MATERIAL AND METHODS: This prospective study was conducted
      on a group of 50 patients diagnosed with pancreatic tumour, who were qualified
      for surgery. RESULTS: From 1.07.2010 to 4.07.2011 a further 50 patients were
      added to the study group. They had been admitted to the hospital with pancreatic
      tumours. During the preoperative period, nine of these people had been treated
      for diabetes, 14 were newly diagnosed with diabetes and 15 had been diagnosed
      with impaired glucose tolerance, but only 12 had a normal glucose profile.
      Afterwards, patients underwent the surgical treatment. Histopathological
      examination revealed that out of the 50 operated patients, 36 suffered from
      malignant disease, and of these only four had no impaired glucose tolerance
      before treatment. CONCLUSIONS: In most cases, patients with pancreatic tumours
      have impaired glucose tolerance. Screening patients over 50 years of age could
      speed up diagnosis and surgical treatment.

PMID- 25061492
TI  - The effect of biliary stenting on difficult common bile duct stones.
AB  - INTRODUCTION: If common bile duct (CBD) stones (choledocholithiasis) are left
      untreated, they may cause increases in morbidity and mortality due to several
      conditions. AIM: In this study, using transient biliary stenting following the
      failure of an initial endoscopic retrograde cholangiopancreatography (ERCP)
      session, we aimed to show the effects of making the CBD stones smaller and easier
      to remove in the following session. MATERIAL AND METHODS: In 156 of 1300 (12%)
      patients with CBD stones, who underwent balloon screening and/or basket
      lithotripsy following ERCP and CBD cannulation, it was not possible to remove the
      stones in the first session. Of these 156 patients, 64 (4.9%) were further
      followed and tested following transient biliary stenting. RESULTS: In the last
      ERCP following biliary stenting, the maximum stone sizes and stone indices were
      decreased in 54 (83%) patients and stone fragmentation was observed in 46 (72%)
      patients. Complete and incomplete removal was obtained in 40 (62.5%) and 24
      (37.5%) patients, respectively. CONCLUSIONS: Biliary stenting, fragmentation and
      the reduction in the size of difficult common bile duct stones caused by the
      first session of ERCP may increase the chance of success in the next session of
      ERCP.

PMID- 25061493
TI  - Moulded calculus of common bile duct mimicking a stenosis.
AB  - Bile duct stenosis, in most cases, appears to be the consequence of pancreatic
      head, ampulla of Vater and bile duct tumours, cholangitis sclerosans, as well as
      iatrogenic damages, which may all be diagnosed during endoscopic retrograde
      cholangiopancreatography (ERCP). In very rare cases the restriction may result
      from an atypically shaped wedged stone. This situation creates many diagnostic
      problems, which in the majority of cases can be solved using imaging studies.
      However, in some patients even a significant extension of diagnostic procedures
      may not lead to a correct diagnosis. We present a diagnostically difficult case
      of a deposit imitating restriction. We present a 70-year-old woman with common
      bile duct restriction undiagnosed despite several ultrasound examinations (USG),
      computed tomography (CT), double magnetic resonance cholangiopancreatography
      (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). Only after the
      third ERCP examination a fragmented, by formerly introduced prosthesis, deposit,
      imitating narrowing, was revealed. Identification of bile duct deposits depends
      on their composition, localisation and the imaging techniques used. Pigment
      calculi with atypical shape, bile density, air density or surrounding tissue
      density are very difficult to diagnose. Thus, the sensitivity of common bile duct
      stone detection in USG, CT, MRCP and endoscopic ultrasound (EUS) is 5-88%; 6-88%;
      73-97%; and 84-98%, respectively. Moreover, ERCP may not diagnose the character
      of the restriction even in 5.2% up to 30% of the patients. Consequently,
      assessment of diagnosis in a number of patients is difficult. A deposit imitating
      common bile duct (CBD) restriction is a rare, difficult to diagnose phenomenon,
      which should be taken into account during differential diagnosis of CBD
      restrictions. 

PMID- 25061494
TI  - Hepatotoxicity caused by montelukast in a paediatric patient.
AB  - Montelukast is a selective and competitive cysteinyl leukotriene receptor
      antagonist (CystLTRA) which is increasingly used for the treatment of allergic
      asthma. Recently, hepatotoxicity has been reported with this drug in adult
      patients, but only one letter to the editor has reported a case of probable
      montelukast-induced hepatotoxicity in a child. We present a case of a 3.5-year
      old boy, receiving treatment with montelukast, who developed hepatocellular
      injury. The exclusion of other causes of increased activity of aminotransferases
      (viral, metabolic, autoimmune), improvement after dechallenge, the morphological
      findings and previous reports of comparable cases support the diagnosis of
      montelukast-induced liver injury in this boy. Physicians should strictly analyse
      indications for this drug and be aware of potential drug-induced liver disease
      caused by this agent. Therefore, the periodical assessment of aminotransferases
      should be recommended during treatment with this leukotriene modifier. 

PMID- 25061495
TI  - Idiopathic scrotal hematoma simulating a testicular torsion, in association with
      cryptorchidism: US findings.
AB  - BACKGROUND: An acute scrotum concerns endoscrotal organs (testicles, spermatic
      cord, tunica vaginalis) and is characterized by pain, swelling and hyperemia of
      the hemi-scrotum. It represents one of the most common surgical emergencies in
      children often caused by testicular torsion; the diagnosis is mostly clinical but
      must be supported by ultrasonographic examination of the scrotal region in
      association with a colour Doppler study of the spermatic cord vessels and
      glandular parenchyma. An idiopathic scrotal hematoma is a very rare condition
      that can simulate it. CASE REPORT: A 3-day-old full-term baby, otherwise in good
      health, showed swelling and pain of the left inguinal-scrotal region. A
      testicular torsion was suspected, so the baby underwent an ultrasound examination
      of the testis and spermatic cord that showed a left scrotal hematoma with
      superior displacement of the didymus; the right testicle was located in the
      internal inguinal canal. Surgical intervention confirmed the sonographic
      diagnosis of left testicular hematoma and of the right cryptorchidism.
      CONCLUSIONS: Although testicular torsion is the most frequent cause of acute
      scrotum, the possibility of a persistent idiopathic scrotal haematoma and/or
      haematoma secondary to a trauma of the inguino-scrotal region, must be always
      taken into account. US diagnosis can avoid unnecessary emergency surgical
      treatment, required in case of testicular torsion.

PMID- 25061496
TI  - Quenched Assembly of NIR-Active Gold Nanoclusters Capped with Strongly Bound
      Ligands by Tuning Particle Charge via pH and Salinity.
AB  - Gold nanospheres coated with a binary monolayer of bound citrate and cysteine
      ligands were assembled into nanoclusters, in which the size and near-infrared
      (NIR) extinction were tuned by varying the pH and concentration of added NaCl.
      During full evaporation of an aqueous dispersion of 4.5 +/- 1.8 nm Au primary
      particles, the nanoclusters were formed and quenched by the triblock copolymer
      polylactic acid (PLA)(1K)-b-poly(ethylene glycol) (PEG)(10K)-b-PLA(1K), which
      also provided steric stabilization. The short-ranged depletion and van der Waals
      attractive forces were balanced against longer ranged electrostatic repulsion to
      tune the nanocluster diameter and NIR extinction. Upon lowering the pH from 7 to
      5 at a given salinity, the magnitude of the charge on the primary particles
      decreased, such that the weaker electrostatic repulsion increased the
      hydrodynamic diameter and, consequently, NIR extinction of the clusters. At a
      given pH, as the concentration of NaCl was increased, the NIR extinction
      decreased monotonically. Furthermore, the greater screening of the charges on the
      nanoclusters weakened the interactions with PLA(1K)-b-PEG(10K)-b-PLA(1K) and thus
      lowered the amount of adsorbed polymer on the nanocluster surface. The
      generalization of the concept of self-assembly of small NIR-active nanoclusters
      to include a strongly bound thiol and the manipulation of the morphologies and
      NIR extinction by variation of pH and salinity not only is of fundamental
      interest but also is important for optical biomedical imaging and therapy.

PMID- 25061497
TI  - Acute pulmonary embolism caused by enlarged uterine leiomyoma: a rare
      presentation.
AB  - PATIENT: Female, 42. FINAL DIAGNOSIS: Acute pulmonary embolism. SYMPTOMS: Chest
      pain * dyspnea. MEDICATION: Streptokinase * Warfarin. CLINICAL PROCEDURE: .-
      SPECIALTY: Cardiology and Neoplasm. OBJECTIVE: Management of emergency care.
      BACKGROUND: Deep venous thrombosis (DVT) and subsequent pulmonary embolism (PE)
      caused by pelvic vein compression are rare and life-threatening complications of
      leiomyoma of the uterus. CASE REPORT: We report a 42-year-old virgin woman with a
      history of leiomyoma who presented to the emergency department with complaints of
      dyspnea and pleuritic chest pain with transient spotting. On physical
      examination, she had a non-tender abdomen with a 20-week size uterus. Imaging
      investigations revealed an acute DVT in her left leg and a huge uterine-derived
      mass compressing the common iliac veins. Transesophageal echocardiography (TEE)
      demonstrated an echogenic mass in her right pulmonary artery consistent with
      thrombosis. The patient was completely cured using thrombolytic therapy and
      myomectomy, and was well at 1 year after thrombolysis. CONCLUSIONS: PE caused by
      pelvic vein compression is a rare complication of leiomyoma, which should be
      considered. Thrombolytic therapy associated with myomectomy can be implemented
      for treating such cases, and TEE can be used for diagnosing suspected high-risk
      PE.

PMID- 25061498
TI  - Ribosome biogenesis: Achilles heel of cancer?

PMID- 25061499
TI  - Biological significance and therapeutic implication of resveratrol-inhibited Wnt,
      Notch and STAT3 signaling in cervical cancer cells.
AB  - Cervical cancers/CCs are one of the commonest malignancies and the second leading
      cause of cancer-related death in women. Resveratrol inhibits CC cell growth but
      its molecular target(s) remains unclear. Since the signaling pathways mediated by
      STAT3, Notch1 and Wnt2 play beneficial roles in CC formation and progression, the
      effects of resveratrol on them in cervical adenocarcinoma (HeLa) and squamous
      cell carcinoma (SiHa) cells were analyzed. The biological significances of the
      above signaling for HeLa and SiHa cells were evaluated by treating the cells with
      STAT3, Wnt or Notch selective inhibitors. The frequencies of STAT3, Notch and Wnt
      activations in 68 cases of CC specimens and 38 non-cancerous cervical epithelia
      were examined by tissue microarray-based immunohistochemical staining. The
      results revealed that HeLa and SiHa cells treated by 100MUM resveratrol showed
      extensive apoptosis, accompanied with suppression of STAT3, Notch and Wnt
      activations. Growth inhibition and apoptosis were found in HeLa and SiHa
      populations treated by AG490, a STAT3/JAK3 inhibitor but not the ones treated by
      Notch inhibitor L-685,458 or by Wnt inhibitor XAV-939. Immunohistochemical
      staining performed on the tissue microarrays showed that the frequencies of
      Notch1, Notch2, Hes1, Wnt2, Wnt5a and p-STAT3 detection as well as beta-catenin
      nuclear translocation in CC samples were significantly higher than that of
      noncancerous group (p<0.01), while the expression rate of PIAS3 was remarkably
      low in cancer samples (p<0.01). Our results thus demonstrate that STAT3, Wnt and
      Notch signaling are frequently co-activated in human CC cells and specimens and
      resveratrol can concurrently inhibit those signaling activations and meanwhile
      lead cervical squamous cell carcinoma and adenocarcinoma cells to growth arrest
      and apoptosis. STAT3 signaling is more critical for CC cells and is the major
      target of resveratrol because selective inhibition of STAT3 rather than Wnt or
      Notch activation commits SiHa and HeLa cells to apoptosis. 

PMID- 25061500
TI  - HOXA10 is associated with temozolomide resistance through regulation of the
      homologous recombinant DNA repair pathway in glioblastoma cell lines.
AB  - Temozolomide resistance is associated with multiple DNA repair pathways. We
      investigated homeobox (HOX) genes for their role in temozolomide resistance,
      focusing on the homologous recombination (HR) pathway, and we tested their
      therapeutic implications in conjunction with O(6)-methylguanine DNA
      methyltransferase (MGMT) status. Two glioblastoma cell lines with different MGMT
      statuses were used to test the augmented anticancer effect of temozolomide with
      HOXA10 inhibition. In vitro experiments, including gene expression studies with
      RNA interference, were performed to verify the related pathway dynamics. HOXA10
      inhibition reinforced temozolomide sensitivity independent of MGMT status and was
      related to the impaired double-strand DNA breakage repair process resulting from
      the downregulation of Rad51 paralogs. Early growth response 1 (EGR1) and
      phosphatase and tensin homolog (PTEN) were the regulatory mediators between
      HOXA10 and the HR pathway. Moreover, HOXA10 inhibition selectively affected the
      nuclear function of PTEN without interfering with its cytoplasmic function of
      suppressing the phosphoinositide 3-kinase/Akt pathway. The mechanism of HR
      pathway regulation by HOXA10 harbors another target mechanism for overcoming
      temozolomide resistance in glioblastoma patients. 

PMID- 25061501
TI  - NDRG2 overexpression enhances glucose deprivation-mediated apoptosis in breast
      cancer cells via inhibition of the LKB1-AMPK pathway.
AB  - The newly identified tumor suppressor, N-myc downstream-regulated gene 2 (NDRG2),
      has been studied in various cancers because of its anticancer and antimetastasis
      effects. In this study, we examined the effect of NDRG2 expression on cell
      viability in MDA-MB-231 human breast cancer cells under conditions that are
      similar to the microenvironment of solid tumors, which include glucose
      deprivation. NDRG2 overexpression enhanced the pro-apoptotic effects of glucose
      deprivation. Glucose deprivation also induced the activation of AMP-activated
      protein kinase (AMPK), which plays a role in protecting tumor cells from
      metabolic stresses. NDRG2 overexpression strongly reduced glucose deprivation
      induced AMPK phosphorylation and increased the cleavage of poly (ADP-ribose)
      polymerase (PARP), which indicated the induction of apoptosis. The expression of
      a constitutively active form of AMPK effectively blocked glucose deprivation
      induced apoptosis in NDRG2-overexpressing MDA-MB-231 cells. Moreover, NDRG2
      overexpression also enhanced the pro-apoptotic effects of 2-deoxyglucose (2-DG)
      or hypoxia, an inducer of metabolic stresses. Finally, we showed that LKB1 is an
      upstream kinase of AMPK that is involved in the inhibition of glucose deprivation
      induced AMPK activity in NDRG2-overexpressing cells. Our findings collectively
      suggest that NDRG2 is a negative regulator of AMPK activity and functions as a
      sensitizer of glucose deprivation. 

PMID- 25061503
TI  - Mirk kinase inhibition targets ovarian cancer ascites.
AB  - The Mirk/dyrk1B gene is commonly amplified or upregulated in ovarian cancers, and
      Mirk is an active kinase in these cancers. Mirk mediates cancer cell survival by
      decreasing toxic ROS levels through maintaining expression of a series of
      antioxidant genes, possibly through its transcriptional activator functions. Mirk
      has the unusual property of being most active in quiescent cancer cells because
      of marked transcriptional downregulation by Akt/mTOR signaling and by MEK/erk
      signaling in cycling cells. Metastatic ovarian cancer cells form ascites, non
      adherent multicellular aggregates floating within the peritoneal fluid. Most
      ascites cancer cells are in a reversible quiescent, dormant state, suggesting
      that Mirk might be expressed in these quiescent cells and thus a therapeutic
      target. The current studies show that ovarian cancer cell line spheroids that
      mimic ascites cancer spheroids were largely quiescent in G0/G1, and enriched in
      Mirk and the quiescence proteins, p130/Rb2 and the CDKI p27. Mirk kinase
      inhibition in spheroids made from established cell lines and in patient-derived
      ascites cancer cell spheroids reduced spheroid volume, disrupted spheroid
      structure to single cells, increased apoptosis, and decreased cell numbers.
      Earlier studies had shown that the mTOR inhibitor RAD001 increased transcription
      of the Mirk/dyrk1B gene, so treatments combined RAD001 with the most active Mirk
      kinase inhibitor. The number of ascites cells from 9 patients was reduced a
      similar amount by cisplatin, Mirk kinase inhibition or RAD001, but reduced
      substantially more, about 90%, by concurrent treatment with both the Mirk kinase
      inhibitor EHT5372 and RAD001. Addition of RAD001 increased the amount of toxic
      ROS induced by Mirk kinase inhibition. Two ascites samples taken one month apart
      gave similar drug responses, showing reproducibility of the techniques. Thus
      Mirk/dyrk1B kinase may be a therapeutic target in ovarian cancer ascites. 

PMID- 25061504
TI  - Increased expression of Id1 and Id3 promotes tumorigenicity by enhancing
      angiogenesis and suppressing apoptosis in small cell lung cancer.
AB  - Constant deregulation of Id1 and Id3 has been implicated in a wide range of
      carcinomas. However, underlying molecular evidence for the joint role of Id1 and
      Id3 in the tumorigenicity of small cell lung cancer (SCLC) is sparse.
      Investigating the biological significance of elevated expression in SCLC cells,
      we found that Id1 and Id3 co-suppression resulted in significant reduction of
      proliferation rate, invasiveness and anchorage-independent growth. Suppressing
      both Id1 and Id3 expression also greatly reduced the average size of tumors
      produced by transfectant cells when inoculated subcutaneously into nude mice.
      Further investigation revealed that suppressed expression of Id1 and Id3 was
      accompanied by decreased angiogenesis and increased apoptosis. Therefore, the
      SCLC tumorigenicity suppression effect of double knockdown of Id1 and Id3 may be
      regulated through pathways of apoptosis and angiogenesis. 

PMID- 25061502
TI  - Identification of a novel lytic peptide for the treatment of solid tumours.
AB  - Originally known as host defence peptides for their substantial bacteriotoxic
      effects, many cationic antimicrobial peptides also exhibit a potent cytotoxic
      activity against cancer cells. Their mode of action is characterized mostly by
      electrostatic interactions with the plasma membrane, leading to membrane
      disruption and rapid necrotic cell death. In this work, we have designed a novel
      cationic peptide of 27 amino acids (Cypep-1), which shows efficacy against a
      number of cancer cell types, both in vitro and in vivo, while normal human
      fibroblasts were significantly less affected. Surface plasmon resonance
      experiments as well as liposome leakage assays monitored by fluorescence
      spectroscopy revealed a substantial binding affinity of Cypep-1 to negatively
      charged liposomes and induced significant leakage of liposome content after
      exposure to the peptide. The observed membranolytic effect of Cypep-1 was
      confirmed by scanning electron microscopy (SEM) as well as by time-lapse confocal
      microscopy. Pharmacokinetic profiling of Cypep-1 in rats showed a short plasma
      half-life after i.v. injection, followed mainly by retention in the liver, spleen
      and kidneys. Extremely low concentrations within the organs of the central
      nervous system indicated that Cypep-1 did not pass the blood-brain-barrier. Local
      treatment of 4T1 murine mammary carcinoma allografts by means of a single local
      bolus injection of Cypep-1 led to a significant reduction of tumour growth in the
      following weeks and prolonged survival. Detailed histological analysis of the
      treated tumours revealed large areas of necrosis. In sum, our findings show that
      the novel cationic peptide Cypep-1 displays a strong cytolytic activity against
      cancer cells both in vitro and in vivo and thus holds a substantial therapeutic
      potential. 

PMID- 25061505
TI  - MORE THAN MONEY: THE EXPONENTIAL IMPACT OF ACADEMIC TECHNOLOGY TRANSFER.
AB  - Academic technology transfer in its current form began with the passage of the
      Bayh-Dole Act in 1980, which allowed universities to retain ownership of
      federally funded intellectual property. Since that time, a profession has evolved
      that has transformed how inventions arising in universities are treated,
      resulting in significant impact to US society. While there have been a number of
      articles highlighting benefits of technology transfer, now, more than at any
      other time since the Bayh-Dole Act was passed, the profession and the impacts of
      this groundbreaking legislation have come under intense scrutiny. This article
      serves as an examination of the many positive benefits and evolution, both
      financial and intrinsic, provided by academic invention and technology transfer,
      summarized in Table 1.

PMID- 25061507
TI  - Vouchers versus Lotteries: What works best in promoting Chlamydia screening? A
      cluster randomised controlled trial.
AB  - In this cluster randomised trial (N=1060), we tested the impact of financial
      incentives (L5 voucher vs. L200 lottery) framed as a gain or loss to promote
      Chlamydia screening in students aged 18-24 years, mimicking the standard outreach
      approach to student in halls of residence. Compared to the control group (1.5%),
      the lottery increased screening to 2.8% and the voucher increased screening to
      22.8%. Incentives framed as gains were marginally more effective (10.5%) that
      loss-framed incentives (7.1%). This work fundamentally contributes to the
      literature by testing the predictive validity of Prospect Theory to change health
      behaviour in the field.

PMID- 25061506
TI  - Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals
      effects on central and peripheral pathways associated with schizophrenia and
      autism spectrum disorders.
AB  - BACKGROUND: Over the last decade, the transgenic N-methyl-D-aspartate receptor
      (NMDAR) NR1-knockdown mouse (NR1(neo-/-)) has been investigated as a glutamate
      hypofunction model for schizophrenia. Recent research has now revealed that the
      model also recapitulates cognitive and negative symptoms in the continuum of
      other psychiatric diseases, particularly autism spectrum disorders (ASD). As
      previous studies have mostly focussed on behavioural readouts, a molecular
      characterisation of this model will help to identify novel biomarkers or
      potential drug targets. METHODS: Here, we have used multiplex immunoassay
      analyses to investigate peripheral analyte alterations in serum of NR1(neo-/-)
      mice, as well as a combination of shotgun label-free liquid chromatography mass
      spectrometry, bioinformatic pathway analyses, and a shotgun-based 40-plex
      selected reaction monitoring (SRM) assay to investigate altered molecular
      pathways in the frontal cortex and hippocampus. All findings were cross compared
      to identify translatable findings between the brain and periphery. RESULTS:
      Multiplex immunoassay profiling led to identification of 29 analytes that were
      significantly altered in sera of NR1(neo-/-) mice. The highest magnitude changes
      were found for neurotrophic factors (VEGFA, EGF, IGF-1), apolipoprotein A1, and
      fibrinogen. We also found decreased levels of several chemokines. Following this,
      LC-MS(E) profiling led to identification of 48 significantly changed proteins in
      the frontal cortex and 41 in the hippocampus. In particular, MARCS, the
      mitochondrial pyruvate kinase, and CamKII-alpha were affected. Based on the
      combination of protein set enrichment and bioinformatic pathway analysis, we
      designed orthogonal SRM-assays which validated the abnormalities of proteins
      involved in synaptic long-term potentiation, myelination, and the ERK-signalling
      pathway in both brain regions. In contrast, increased levels of proteins involved
      in neurotransmitter metabolism and release were found only in the frontal cortex
      and abnormalities of proteins involved in the purinergic system were found
      exclusively in the hippocampus. CONCLUSIONS: Taken together, this multi-platform
      profiling study has identified peripheral changes which are potentially linked to
      central alterations in synaptic plasticity and neuronal function associated with
      NMDAR-NR1 hypofunction. Therefore, the reported proteomic changes may be useful
      as translational biomarkers in human and rodent model drug discovery efforts.

PMID- 25061508
TI  - rLOAD: does sex mediate the effect of acute antiplatelet loading on stroke
      outcome.
AB  - BACKGROUND: Biologic sex can influence response to pharmacologic therapy. The
      purpose of this proof-of-concept study was to evaluate the medicating effects of
      estrogen in the efficacy of acute antiplatelet loading therapy on stroke outcome
      in the rabbit small clot embolic model. METHODS: Female and male (20/group) New
      Zealand White rabbits were embolized to produce embolic stroke by injecting small
      blood clots into the middle cerebral artery via an internal carotid artery
      catheter. Two hours after embolization, rabbits were treated with standard dose
      antiplatelet loading (aspirin 10 mg/kg plus clopidogrel 10 mg/kg). Primary
      outcome measures were platelet inhibition, behavioral outcome P 50 (the weight of
      microclots (mg) that produces neurologic dysfunction in 50% of a group of
      animals), and effect of endogenous estrogen on outcome. RESULTS: For the first
      time in a non-rodent model of stroke, it was found that higher endogenous
      estrogen levels resulted in significantly better behavioral outcome in female
      subjects (r s -0.70, p < 0.011). Platelet inhibition in response to collagen,
      arachidonic acid, and adenosine diphosphate (ADP) was not significantly different
      in females with higher vs. lower estrogen levels. CONCLUSIONS: Behavioral
      outcomes are improved with females with higher endogenous estrogen levels treated
      with standard dose antiplatelet loading. This is the first non-rodent study to
      demonstrate that higher endogenous estrogen levels in female rabbits appear to be
      neuroprotective in ischemic stroke. This research supports the further study of
      the effect of endogenous estrogen levels on outcome with standard dose
      antiplatelet loading in stroke patients not eligible for revascularization
      therapies.

PMID- 25061509
TI  - Transcriptome profiling identifies ABA mediated regulatory changes towards
      storage filling in developing seeds of castor bean (Ricinus communis L.).
AB  - BACKGROUND: The potential biodiesel plant castor bean (Ricinus communis) has been
      in the limelight for bioenergy research due to the availability of its genome
      which raises the bar for genome-wide studies claiming advances that impact the
      "genome-phenome challenge". Here we report the application of phytohormone ABA as
      an exogenous factor for the improvement of storage reserve accumulation with a
      focus on the complex interaction of pathways associated with seed filling.
      RESULTS: After the application of exogenous ABA treatments, we measured an
      increased ABA levels in the developing seeds cultured in vitro using the ELISA
      technique and quantified the content of major biomolecules (including total
      lipids, sugars and protein) in treated seeds. Exogenous ABA (10 MUM) enhanced the
      accumulation of soluble sugar content (6.3%) followed by deposition of total
      lipid content (4.9 %). To elucidate the possible ABA signal transduction pathways
      towards overall seed filling, we studied the differential gene expression
      analysis using Illumina RNA-Sequencing technology, resulting in 2568 (1507
      up/1061-down regulated) differentially expressed genes were identified. These
      genes were involved in sugar metabolism (such as glucose-6-phosphate, fructose
      1,6 bis-phosphate, glycerol-3-phosphate, pyruvate kinase), lipid biosynthesis
      (such as ACS, ACBP, GPAT2, GPAT3, FAD2, FAD3, SAD1 and DGAT1), storage proteins
      synthesis (such as SGP1, zinc finger protein, RING H2 protein, nodulin 55 and
      cytochrome P450), and ABA biosynthesis (such as NCED1, NCED3 and beta carotene).
      Further, we confirmed the validation of RNA-Sequencing data by Semi-quantitative
      RT-PCR analysis. CONCLUSIONS: Taken together, metabolite measurements supported
      by genes and pathway expression results indicated in this study provide new
      insights to understand the ABA signaling mechanism towards seed storage filling
      and also contribute useful information for facilitating oilseed crop functional
      genomics on an aim for utilizing castor bean agricultural and bioenergy use.

PMID- 25061510
TI  - Molecular mechanism of double Holliday junction dissolution.
AB  - Processing of homologous recombination intermediates is tightly coordinated to
      ensure that chromosomal integrity is maintained and tumorigenesis avoided.
      Decatenation of double Holliday junctions, for example, is catalysed by two
      enzymes that work in tight coordination and belong to the same 'dissolvasome'
      complex. Within the dissolvasome, the RecQ-like BLM helicase provides the
      translocase function for Holliday junction migration, while the topoisomerase III
      alpha-RMI1 subcomplex works as a proficient DNA decatenase, together resulting in
      double-Holliday-junction unlinking. Here, we review the available architectural
      and biochemical knowledge on the dissolvasome machinery, with a focus on the
      structural interplay between its components. 

PMID- 25061511
TI  - Phylogenetic grouping, epidemiological typing, analysis of virulence genes, and
      antimicrobial susceptibility of Escherichia coli isolated from healthy broilers
      in Japan.
AB  - BACKGROUND: The aim of our study was to investigate the possible etiology of
      avian colibacillosis by examining Escherichia coli isolates from fecal samples of
      healthy broilers. FINDINGS: Seventy-eight E. coli isolates from fecal samples of
      healthy broilers in Japan were subjected to analysis of phylogenetic background,
      virulence-associated gene profiling, multi-locus sequence typing (MLST), and
      antimicrobial resistance profiling. Phylogenetic analysis demonstrated that 35 of
      the 78 isolates belonged to group A, 28 to group B1, one to group B2, and 14 to
      group D. Virulence-associated genes iutA, iss, cvaC, tsh, iroN, ompT, and hlyF
      were found in 23 isolates (29.5%), 16 isolates (20.5%), nine isolates (11.5%),
      five isolates (6.4%), 19 isolates (24.4%), 23 isolates (29.5%), and 22 isolates
      (28.2%) respectively. Although the genetic diversity of group D isolates was
      revealed by MLST, the group D isolates harbored iutA (10 isolates, 71.4%), iss (6
      isolates, 42.9%), cvaC (5 isolates, 35.7%), tsh (3 isolates, 21.4%), hlyF (9
      isolates, 64.3%), iroN (7 isolates, 50.0%), and ompT (9 isolates, 64.3%).
      CONCLUSIONS: Our results indicated that E. coli isolates inhabiting the
      intestines of healthy broilers pose a potential risk of causing avian
      colibacillosis.

PMID- 25061512
TI  - High-coverage sequencing and annotated assemblies of the budgerigar genome.
AB  - BACKGROUND: Parrots belong to a group of behaviorally advanced vertebrates and
      have an advanced ability of vocal learning relative to other vocal-learning
      birds. They can imitate human speech, synchronize their body movements to a
      rhythmic beat, and understand complex concepts of referential meaning to sounds.
      However, little is known about the genetics of these traits. Elucidating the
      genetic bases would require whole genome sequencing and a robust assembly of a
      parrot genome. FINDINGS: We present a genomic resource for the budgerigar, an
      Australian Parakeet (Melopsittacus undulatus) -- the most widely studied parrot
      species in neuroscience and behavior. We present genomic sequence data that
      includes over 300* raw read coverage from multiple sequencing technologies and
      chromosome optical maps from a single male animal. The reads and optical maps
      were used to create three hybrid assemblies representing some of the largest
      genomic scaffolds to date for a bird; two of which were annotated based on
      similarities to reference sets of non-redundant human, zebra finch and chicken
      proteins, and budgerigar transcriptome sequence assemblies. The sequence reads
      for this project were in part generated and used for both the Assemblathon 2
      competition and the first de novo assembly of a giga-scale vertebrate genome
      utilizing PacBio single-molecule sequencing. CONCLUSIONS: Across several quality
      metrics, these budgerigar assemblies are comparable to or better than the chicken
      and zebra finch genome assemblies built from traditional Sanger sequencing reads,
      and are sufficient to analyze regions that are difficult to sequence and
      assemble, including those not yet assembled in prior bird genomes, and promoter
      regions of genes differentially regulated in vocal learning brain regions. This
      work provides valuable data and material for genome technology development and
      for investigating the genomics of complex behavioral traits.

PMID- 25061513
TI  - Effect of chemotherapy on the microbiota and metabolome of human milk, a case
      report.
AB  - BACKGROUND: Human milk is an important source of bacteria for the developing
      infant and has been shown to influence the bacterial composition of the neonatal
      gut, which in turn can affect disease risk later in life. Human milk is also an
      important source of nutrients, influencing bacterial composition but also
      directly affecting the host. While recent studies have emphasized the adverse
      effects of antibiotic therapy on the infant microbiota, the effects of maternal
      chemotherapy have not been previously studied. Here we report the effects of drug
      administration on the microbiota and metabolome of human milk. METHODS: Mature
      milk was collected every two weeks over a four month period from a lactating
      woman undergoing chemotherapy for Hodgkin's lymphoma. Mature milk was also
      collected from healthy lactating women for comparison. Microbial profiles were
      analyzed by 16S sequencing and the metabolome by gas chromatography-mass
      spectrometry. FINDINGS: Chemotherapy caused a significant deviation from a
      healthy microbial and metabolomic profile, with depletion of genera
      Bifidobacterium, Eubacterium, Staphylococcus and Cloacibacterium in favor of
      Acinetobacter, Xanthomonadaceae and Stenotrophomonas. The metabolites
      docosahexaenoic acid and inositol known for their beneficial effects were also
      decreased. CONCLUSION: With milk contents being critical for shaping infant
      immunity and development, consideration needs to be given to the impact of drugs
      administered to the mother and the long-term potential consequences for the
      health of the infant.

PMID- 25061514
TI  - The dynamics of a family's gut microbiota reveal variations on a theme.
AB  - BACKGROUND: It is clear that the structure and function of the human microbiota
      has significant impact on maintenance of health and yet the factors that give
      rise to an adult microbiota are poorly understood. A combination of genetics,
      diet, environment, and life history are all thought to impact the development of
      the gut microbiome. Here we study a chronosequence of the gut microbiota found in
      eight individuals from a family consisting of two parents and six children
      ranging in age from two months to ten years old. RESULTS: Using 16S rRNA gene and
      metagenomic shotgun sequence data, it was possible to distinguish the family from
      a cohort of normal individuals living in the same geographic region and to
      differentiate each family member. Interestingly, there was a significant core
      membership to the family members' microbiota where the abundance of this core
      accounted for the differences between individuals. It was clear that the
      introduction of solids represents a significant transition in the development of
      a mature microbiota. This transition was associated with increased diversity,
      decreased stability, and the colonization of significant abundances of
      Bacteroidetes and Clostridiales. Although the children and mother shared
      essentially the identical diet and environment, the children's microbiotas were
      not significantly more similar to their mother than they were to their father.
      CONCLUSIONS: This analysis underscores the complex interactions that give rise to
      a personalized microbiota and suggests the value of studying families as a
      surrogate for longitudinal studies.

PMID- 25061515
TI  - Radiation oncology in Latin speaking countries: A link between Europe and Latin
      America.

PMID- 25061516
TI  - Toxicity outcome in patients treated with modulated arc radiotherapy for
      localized prostate cancer.
AB  - AIM: This study evaluates the acute toxicity outcome in patients treated with
      RapidArc for localized prostate cancer. BACKGROUND: Modern technologies allow the
      delivery of high doses to the prostate while lowering the dose to the
      neighbouring organs at risk. Whether this dosimetric advantage translates into
      clinical benefit is not well known. MATERIALS AND METHODS: Between December 2009
      and May 2012, 45 patients with primary prostate adenocarcinoma were treated using
      RapidArc. All patients received 1.8 Gy per fraction, the median dose to the
      prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy
      (range, 77.4-81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6-79.2 Gy),
      respectively. RESULTS: The time between the last session and the last treatment
      follow up was a median of 10 months (range, 3-24 months). The incidence of grade
      3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%,
      respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of
      patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older
      patients (>median) or patients with V60 higher than 35% had significantly higher
      rates of grade >=2 acute GI toxicity compared with the younger ones. CONCLUSIONS:
      RapidArc in the treatment of localized prostate cancer is tolerated well with no
      Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had
      significantly higher rates of grade >=2 acute GI toxicity. Further research is
      necessary to assess definitive late toxicity and tumour control outcome.

PMID- 25061517
TI  - Intraoperative radiation therapy opportunities for clinical practice
      normalization: Data recording and innovative development.
AB  - BACKGROUND: Intraoperative radiotherapy (IORT) refers to the delivery of a high
      dose of radiation at the time of surgery. AIM: To analyze clinical and research
      oriented innovative activities developed in a 17-year period using intraoperative
      electron-radiation therapy (IOeRT) as a component of treatment in a
      multidisciplinary approach for cancer management. MATERIALS AND METHODS: From
      01/1995 to 03/2012 IOeRT procedures were registered in a specific Hospital-based
      database. Research and developments in imaging and recording for treatment
      planning implementation are active since 2006. RESULTS: 1004 patients were
      treated and 1036 IORT procedures completed. Median age of patients was 61 (range
      5 months to 94 years). Gender distribution was male in 54% of cases and female in
      46%. Disease status at the time of IORT was 796 (77%) primary and 240 (23%)
      recurrent. Cancer type distribution included: 62% gastrointestinal, 18% sarcoma,
      5% pancreas, 2% paediatric, 3% breast, 77 7% oligotopic recurrences, 2% other.
      IORT technical characteristics were: Applicator size 5 cm 22%, 6 cm 21%, 7 cm
      21%, 8 cm 15%, 9 cm 6%, 10 cm 7% 12 cm 5% 15 cm 3%. Electron energies: 6 MeV 19%,
      8 MeV 15%, 10 MeV 15%, 12 MeV 23%, 15 MeV 19%, 18 MeV 6%, other 3%. Multiple
      fields: 108 (11%). Dose: 7.5 Gy 3%, 10 Gy 35%, 12 Gy 3%, 12.5 Gy 49%, 15 Gy 5%,
      other 5%. CONCLUSION: An IORT programme developed in an Academic Hospital based
      on practice-oriented medical decisions is an attractive interdisciplinary
      oncology initiative proven to be able to generate an intensive clinical activity
      for cancer patient quality care and a competitive source of scientific patient
      oriented research, development and innovation.

PMID- 25061518
TI  - Intraoperative radiation therapy, opportunities for clinical practice
      normalization: MEDTING, a scientific platform.
AB  - AIM: To use a platform to analyze a subgroup specialized in evaluation of
      patients candidates to IOERT. BACKGROUND: Medting is a project that was initiated
      to support daily clinical activity, knowledge management and medical education by
      sharing information with other physicians. The project began at the "Hospital
      General Universitario Gregorio Maranon", which has a dedicated oncology
      physician's multi-specialist committee. There are many scientific social networks
      all over the world. Medting is the only platform that specializes in healthcare
      and has been developed for hospital purposes. MATERIALS AND METHODS: Medting
      brings all together the relevant clinical information from electronic medical
      records and picture archiving about the patient to study. Subplatform Medting
      IORT was created on February 2, 2012 at the Hospital General Universitario
      Gregorio Maranon. It has 23 members, have been registered 18 cases with 238
      multimedia images. RESULTS: Medting started with 28 physicians and five
      departments. After 6 months, proof of concept period, there are 225 physicians,
      more than 120 medical students and 39 departments in 3 hospitals using the
      scientific social network. Furthermore, the project is being extended on three
      more hospitals in Madrid. CONCLUSION: Medting gives the opportunity to oncology
      physicians to access all relevant clinical information with the ability to
      discuss case notes and view images at any time. The impact of the Medting
      platform in a subgroup working team to evaluate IOERT patients candidates is
      included in the analysis. The use of a constantly updated repository based on
      real cases and the documentation of the internal activity of the tumor committee
      beyond the medical record, has become an extraordinary tool for teaching,
      training and learning.

PMID- 25061519
TI  - Evidence based radiation oncology with existing technology.
AB  - AIM: To assess the real contribution of modern radiation therapy (RT) technology
      in the more common tumoral types in Central America, Caribbean and South America.
      BACKGROUND: RT is an essential tool in the management of cancer. RT can be either
      palliative or of curative intent. In general, for palliative radiotherapy, major
      technologies are not needed. MATERIALS AND METHODS: We analyzed the contribution
      of RT technology based on published evidence for breast, lung, gastric,
      gallbladder, colorectal, prostate and cervix cancer in terms of disease control,
      survival or toxicity with especial focus on Latin America. RESULTS: Findings
      indicate that three dimensional conformal radiation therapy (3D RT) is the gold
      standard in most common type of cancer in the studied regions. Prostate cancer is
      probably the pathology that has more benefits when using new RT technology such
      as intensity modulated radiation therapy (IMRT) versus 3DRT in terms of toxicity
      and biochemical progression-free survival. CONCLUSIONS: In light of the changes
      in technology, the ever-increasing access of developing countries to such
      technology, and its current coverage in Latin America, any efforts in this area
      should be aimed at improving the quality of the radiotherapy departments and
      centers that are already in place.

PMID- 25061520
TI  - Rare breast tumors: Review of the literature.
AB  - Breast cancer tumors have different morphological phenotypes and specific
      histopathological types with particular prognostic and clinical characteristics.
      The treatment of rare malignant lesions is frequently controversial due to the
      absence of trials to determine the optimal managements. This review describes the
      spectrum of rare breast tumors indicating the clinical, epidemiological and
      treatment characteristics. 

PMID- 25061521
TI  - Is stereotactic ablative radiotherapy an alternative to surgery in operable stage
      I non-small cell lung cancer?
AB  - Surgery is the gold therapeutic standard for patients affected with stage I non
      small cell lung cancer. Stereotactic ablative radiotherapy is currently
      considered the preferred treatment option for inoperable patients, representing
      approximately 25%. Limited data are available directly comparing surgery and SABR
      in operable patients, none of them prospective. Preliminary results are
      encouraging, showing that the two treatment modalities are equally effective in
      terms of tumour control, with expected similar survival projections. Moreover, in
      elderly patients SABR could represent a valid treatment alternative in comparison
      to surgery due to the lower morbidity. We here review and discuss the potential
      role of SABR as an alternative to surgery in operable early stage lung cancer
      patients. 

PMID- 25061522
TI  - Radio-chemotherapy in anal cancer: Institutional experience at a large radiation
      oncology center in Chile.
AB  - AIM: In this article the aim is to provide a concise narrative review and inform
      the institutional experience at a referral center in Chile with the use of radio
      chemotherapy in anal cancer. BACKGROUND: Cancer of the anus and anal canal is
      mainly a loco-regional disease. For years the standard of care has been
      concomitant radio-chemotherapy, which permits organ preservation and better local
      control than alternative surgical procedures. MATERIALS AND METHODS: A
      retrospective analysis of 44 patients treated between 2002 and 2010 was
      performed. Local recurrence, distant recurrence and overall survival were
      analyzed with the Kaplan-Meier method. Relevant groups where compared with the
      log-rank test and univariate analysis were done with the Cox proportional hazards
      model. RESULTS: Median follow-up of the cohort was 56 months, with a minimum
      follow-up of at least 24 months. There was a significant difference between
      clinical stages in disease free survival (log-rank trend p < 0.001), and a
      significant difference in overall survival (OS) when comparing clinical stages
      that were grouped in stage I-IIIa and IIIB (log-rank p = 0.001). On univariate
      analysis, age older than 60, having received full treatment and dose above 45 Gy
      were all significantly related to OS (p < 0.05). An overall survival of 45% and
      disease free survival of 45% at 5 years were found in our series. CONCLUSIONS:
      Our findings show that results at the Instituto de Radiomedicina in Chile are
      comparable to published literature. Dismal results in stage IIIb cases indicate
      much work remains in therapies to achieve loco-regional control in locally
      advanced cases.

PMID- 25061523
TI  - Combined Tractional and Rhegmatogenous Retinal Detachment in Proliferative
      Diabetic Retinopathy in the Anti-VEGF Era.
AB  - Purpose. To investigate the clinical features, surgical outcomes, and prognostic
      factors of combined rhegmatogenous and tractional detachment (combined RD) in
      proliferative diabetic retinopathy (PDR) in recent years. Methods. Medical
      records of PDR and combined RD treated with vitrectomy from 2008 to 2013 were
      retrospectively reviewed. Results. A total of 57 eyes from 49 patients were
      included. Nine eyes had received panretinal photocoagulation (PRP) and 7 eyes had
      intravitreal bevacizumab (IVB) within 3 months before RD developed. Thirty-eight
      eyes (66.7%) had ?3 sites of broad adhesion of fibrovascular proliferation (FVP).
      Thirty-three eyes (57.9%) showed active FVP. Thirty-four eyes (59.6%) had extent
      of RD involving 3 or 4 quadrants. The primary reattachment rate was 93.0%, and
      the final visual acuity (VA) improved by more than 3 lines in 80.7% of eyes.
      Neovascular glaucoma occurred in 4 eyes postoperatively. Poor preoperative VA,
      severe vitreoretinal adhesion, and broad extent of RD had significant correlation
      with poor visual outcomes. Conclusion. PRP or IVB might play a role in provoking
      combined RD. The anatomical and functional success rates of surgery were high.
      Poor preoperative VA and severe proliferations predicted poor visual outcomes. 

PMID- 25061525
TI  - The effect of a nurse-led multidisciplinary team on ventilator-associated
      pneumonia rates.
AB  - Background. Ventilator-associated pneumonia (VAP) is a worrisome, yet potentially
      preventable threat in critically ill patients. Evidence-based clinical practices
      targeting the prevention of VAP have proven effective, but the most optimal
      methods to ensure consistent implementation and compliance remain unknown.
      Methods. A retrospective study of the trend in VAP rates in a community
      hospital's open medical intensive care unit (MICU) after the enactment of a nurse
      led VAP prevention team. The period of the study was between April 1, 2009, and
      September 30, 2012. The team rounded on mechanically ventilated patients every
      Tuesday and Thursday. They ensured adherence to the evidence-based VAP
      prevention. A separate and independent infection control team monitored VAP
      rates. Results. Across the study period, mean VAP rate was 3.20/1000 ventilator
      days +/-5.71 SD. Throughout the study time frame, there was an average monthly
      reduction in VAP rate of 0.27/1000 ventilator days, P < 0.001 (CI: -0.40--0.13).
      Conclusion. A nurse-led interdisciplinary team dedicated to VAP prevention
      rounding twice a week to ensure adherence with a VAP prevention bundle lowered
      VAP rates in a community-hospital open MICU. The team had interdepartmental and
      administrative support and addressed any deficiencies in the VAP prevention
      bundle components actively. 

PMID- 25061526
TI  - Long-term effects of the treatment of depressive female inpatients in a
      naturalistic study: is early improvement a valid predictor of outcome?
AB  - Objectives. To examine the predictive value of early improvement for short- and
      long-term outcome in the treatment of depressive female inpatients and to explore
      the influence of comorbid disorders (CD). Methods. Archival data of a
      naturalistic sample of 277 female inpatients diagnosed with a depressive disorder
      was analyzed assessing the BDI at baseline, after 20 days and 30 days,
      posttreatment, and after 3 to 6 months at follow-up. Early improvement, defined
      as a decrease in the BDI score of at least 30% after 20 and after 30 days, and CD
      were analyzed using binary logistic regression. Results. Both early improvement
      definitions were predictive of remission at posttreatment. Early improvement
      after 30 days showed a sustained treatment effect in the follow-up phase, whereas
      early improvement after 20 days failed to show a persistent effect regarding
      remission at follow-up. CD were not significantly related neither at
      posttreatment nor at follow-up. At no time point CD moderated the prediction by
      early improvement. Conclusions. We show that early improvement is a valid
      predictor for short-term remission and at follow-up in an inpatient setting. CD
      did not predict outcome. Further studies are needed to identify patient subgroups
      amenable to more tailored treatments. 

PMID- 25061524
TI  - Exercise and dietary-mediated reductions in postprandial lipemia.
AB  - Postprandial hyperlipemia produces long-term derangements in lipid/lipoprotein
      metabolism, vascular endothelial dysfunction, hypercoagulability, and sympathetic
      hyperactivity which are strongly linked to atherogenesis. The purpose of this
      review is to (1) provide a qualitative analysis of the available literature
      examining the dysregulation of postprandial lipid metabolism in the presence of
      obesity, (2) inspect the role of adiposity distribution and sex on postprandial
      lipid metabolism, and (3) examine the role of energy deficit (exercise- and/or
      energy restriction-mediated), isoenergetic low-carbohydrate diets, and omega-3 (n
      3) fatty acid supplementation on postprandial lipid metabolism. We conclude from
      the literature that central adiposity primarily accounts for sex-related
      differences in postprandial lipemia and that aerobic exercise attenuates this
      response in obese or lean men and women to a similar extent through potentially
      unique mechanisms. In contrast, energy restriction produces only mild reductions
      in postprandial lipemia suggesting that exercise may be superior to energy
      restriction alone as a strategy for lowering postprandial lipemia. However,
      isoenergetic very low-carbohydrate diets and n-3 fatty acid supplementation
      reduce postprandial lipemia indicating that macronutrient manipulations reduce
      postprandial lipemia in the absence of energy restriction. Therefore,
      interactions between exercise/energy restriction and alterations in macronutrient
      content remain top priorities for the field to identify optimal behavioral
      treatments to reduce postprandial lipemia. 

PMID- 25061527
TI  - Polyphenols from Berries of Aronia melanocarpa Reduce the Plasma Lipid
      Peroxidation Induced by Ziprasidone.
AB  - Background. Oxidative stress in schizophrenia may be caused partially by the
      treatment of patients with antipsychotics. The aim of the study was to establish
      the effects of polyphenol compounds derived from berries of Aronia melanocarpa
      (Aronox) on the plasma lipid peroxidation induced by ziprasidone in vitro.
      Methods. Lipid peroxidation was measured by the level of thiobarbituric acid
      reactive species (TBARS). The samples of plasma from healthy subjects were
      incubated with ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml) alone and with
      Aronox (5 ug/ml; 50 ug/ml). Results. We observed a statistically significant
      increase of TBARS level after incubation of plasma with ziprasidone (40 ng/ml;
      139 ng/ml; and 250 ng/ml) (after 24 h incubation: P = 7.0 * 10(-4), P = 1.6 * 10(
      3), and P = 2.7 * 10(-3), resp.) and Aronox lipid peroxidation caused by
      ziprasidone was significantly reduced. After 24-hour incubation of plasma with
      ziprasidone (40 ng/ml; 139 ng/ml; and 250 ng/ml) in the presence of 50 ug/ml
      Aronox, the level of TBARS was significantly decreased: P = 6.5 * 10(-8), P = 7.0
      * 10(-6), and P = 3.0 * 10(-5), respectively. Conclusion. Aronox causes a
      distinct reduction of lipid peroxidation induced by ziprasidone. 

PMID- 25061528
TI  - Noninvasive and multidisciplinary approach to the functional and esthetic
      rehabilitation of amelogenesis imperfecta: a pediatric case report.
AB  - Case Report. An 8-year-old girl with amelogenesis imperfecta (AI) reported
      unsatisfactory aesthetics, difficulty in mastication, and dental
      hypersensitivity. The intraoral examination observed mixed dentition,
      malocclusion in anteroposterior relationships, anterior open bite, and dental
      asymmetry. A hypoplastic form of AI was diagnosed in the permanent dentition. A
      multidisciplinary planning was performed and divided into preventive, orthopedic,
      and rehabilitation stages. Initially, preventive treatment was implemented, with
      fluoride varnish applications, in order to protect the fragile enamel and reduce
      the dental sensitivity. In the second stage, the patient received an interceptive
      orthopedic treatment to improve cross-relationship of the arches during six
      months. Finally, the rehabilitation treatment was executed to establish the
      vertical dimension. In the posterior teeth, indirect composite resin crowns were
      performed with minimally invasive dental preparation. Direct composite resin
      restorations were used to improve the appearance of anterior teeth. Follow-Up.
      The follow-up was carried out after 3, 6, 12, and 18 months. After 18 months of
      follow-up, The restoration of integrity, oral hygiene, and patient satisfaction
      were observed . Conclusion. Successful reduction of the dental hypersensitivity
      and improvement of the aesthetic and functional aspects as well as quality of
      life were observed. 

PMID- 25061529
TI  - Impression material mass retained in the mucobuccal fold.
AB  - Trapped foreign bodies and tissue reactions to foreign materials are commonly
      encountered in the oral cavity. Traumatically introduced dental materials,
      instruments, or needles are the most common materials referred to in the dental
      literature. This paper describes an iatrogenic foreign body encapsulation in the
      oral mucosa, clinically appearing as 5 * 10 mm tumor-like swelling with an intact
      overlying epithelium and diagnosed as a polymeric impression material. Detailed
      case history and, clinical and radiographic examinations including CBCT and
      spectrometric analysis of the retrieved sample were necessary to determine
      accurately the nature, size, and location of the foreign body. It is suggested
      that the origin of the material relates to an impression made 2 years ago,
      leaving a mass trapped in a traumatized mucosal tissue. 

PMID- 25061530
TI  - Axillary artery injury caused by fracture of humerus neck and its repair using
      basilic vein graft.
AB  - Proximal humerus fractures are rarely associated with axillary artery injury. We
      present a case of a 59-year-old female who had fracture neck humerus along with
      absent pulsations in the left upper limb after blunt trauma. Computed tomographic
      angiogram revealed complete occlusion of the left axillary artery. Urgent
      surgical intervention was done in the form of fixation of fracture followed by
      exploration and repair of axillary artery. Axillary artery was contused and
      totally occluded by fractured edge of humerus. Repair of the axillary artery was
      done using basilic vein graft harvested through the same incision. Postprocedure
      pulsations were present in the upper limb. 

PMID- 25061531
TI  - Middle segment-preserving pancreatectomy for recurrent metastasis of renal cell
      carcinoma after pancreatoduodenectomy: a case report.
AB  - Many cases of surgical resection of metastatic pancreatic tumors originating from
      renal cell carcinoma have been reported; however, cases of reresection of
      recurrent pancreatic metastasis of renal cell carcinoma in the remnant pancreas
      are rare. We performed a second resection for recurrent pancreatic metastasis of
      renal cell carcinoma six years after pancreatoduodenectomy with
      pancreaticogastrostomy reconstruction. By performing middle segment-preserving
      pancreatectomy, we were able to successfully spare the exocrine and endocrine
      pancreatic function compared to that observed after total pancreatectomy, with no
      signs of recurrence for two years after the surgery. 

PMID- 25061532
TI  - Differing tales of two patients after receiving a kidney transplant from a donor
      with disseminated intravascular coagulation.
AB  - In order to decrease the time on the deceased donor kidney wait list and to have
      more organs available, criteria for acceptable organs for transplant could be
      made less stringent. There are reports of successful recipient outcomes using
      kidney donors presenting with disseminated intravascular coagulation (DIC). We
      report a unique circumstance where two patients received kidneys from the same
      deceased donor who had DIC; one patient developed thrombotic microangiopathy
      (TMA) while the other did not. This difference in outcome may indicate that both
      donor and recipient factors contribute to the development of posttransplant TMA. 

PMID- 25061533
TI  - Conservative management of a delayed neovesicocutaneous fistula.
AB  - A neovesicocutaneous fistula is a rare complication after orthotopic bladder
      reconstruction, particularly in the late postoperative period. We report the case
      of a 59-year-old man who had undergone ileal neobladder construction 17 months
      previously. He presented with urinary retention concomitant with urinary tract
      infection due to a neovesicourethral anastomotic stricture. After a combination
      of transurethral catheter drainage and broad-spectrum antibiotic therapy for 3
      weeks, the fistulous tract completely closed. Therefore, conservative treatment
      may be regarded as a valid option for a delayed neovesicocutaneous fistula. 

PMID- 25061534
TI  - Neuroprotective Properties of a Standardized Extract from Myracrodruon urundeuva
      Fr. All. (Aroeira-Do-Sertao), as Evaluated by a Parkinson's Disease Model in
      Rats.
AB  - Myracrodruon urundeuva Fr. All. (Anacardiaceae) is a Brazilian medicinal species,
      which is common to the Northeastern Brazilian semiarid region, whose stem-bark is
      widely used in folk medicine. It is an endangered species, presenting as main
      bioactive components tannins and chalcones. In this work, we studied the
      neuroprotective effects of a standardized extract from cultivated M. urundeuva
      (SEMU), in a model of Parkinson's disease. Thus, a unilateral injection of 6-OHDA
      was done into the rat right stratum. The animals were submitted to stereotaxic
      surgery, then treated with SEMU (5, 10, 20, or 40 mg/kg, p.o.) for 2 weeks,
      subjected to behavioral tests, and euthanized for striata dissections and
      neurochemical, histological, and immunohistochemical analyses. We showed, for the
      first time, that SEMU reverted behavioral alterations seen in the 6-OHDA-lesioned
      group and partially blocked the decrease in DA and DOPAC contents. The numbers of
      viable neurons and TH immunopositive cells were increased by SEMU. In addition,
      the SEMU-treated 6-OHDA groups showed lower numbers of GFAP and OX-42
      immunopositive cells. The neuroprotective action of SEMU is possibly related to
      the antioxidant and anti-inflammatory properties of M. urundeuva, pointing out to
      its potential use in the prevention or treatment of neurodegenerative conditions,
      such as Parkinson's disease. 

PMID- 25061535
TI  - Mouse models of gastric carcinogenesis.
AB  - Gastric cancer is one of the most common cancers in the world. Animal models have
      been used to elucidate the details of the molecular mechanisms of various
      cancers. However, most inbred strains of mice have resistance to gastric
      carcinogenesis. Helicobacter infection and carcinogen treatment have been used to
      establish mouse models that exhibit phenotypes similar to those of human gastric
      cancer. A large number of transgenic and knockout mouse models of gastric cancer
      have been developed using genetic engineering. A combination of carcinogens and
      gene manipulation has been applied to facilitate development of advanced gastric
      cancer; however, it is rare for mouse models of gastric cancer to show
      aggressive, metastatic phenotypes required for preclinical studies. Here, we
      review current mouse models of gastric carcinogenesis and provide our
      perspectives on future developments in this field. 

PMID- 25061537
TI  - Comparison of short-term postoperative outcomes in totally laparoscopic distal
      gastrectomy versus laparoscopy-assisted distal gastrectomy.
AB  - PURPOSE: The advantages of totally laparoscopic surgery in early gastric cancer
      (EGC) are unproven, and some concerns remain regarding the oncologic safety and
      technical difficulty. This study aimed to evaluate the technical feasibility and
      clinical benefits of totally laparoscopic distal gastrectomy (TLDG) for the
      treatment of gastric cancer compared with laparoscopy-assisted distal gastrectomy
      (LADG). MATERIALS AND METHODS: A retrospective review of 211 patients who
      underwent either TLDG (n=134; 63.5%) or LADG (n=77; 36.5%) for EGC between April
      2005 and October 2013 was performed. Clinicopathologic features and surgical
      outcomes were analyzed and compared between the groups. RESULTS: The operative
      time in the TLDG group was significantly shorter than that in the LADG group (193
      [range, 160~230] vs. 215 minutes [range, 170~255]) (P=0.021). The amount of blood
      loss during TLDG was estimated at 200 ml (range, 100~350 ml), which was
      significantly less than that during LADG, which was estimated at 400 ml (range,
      400~700 ml) (P<0.001). The hospital stay in the TLDG group was shorter than that
      in the LADG group (7 vs. 8 days, P<0.001). One patient from each group underwent
      laparotomic conversion. Two patients in the TLDG group required reoperation: one
      for hemostasis after intraabdominal bleeding and 1 for repair of wound dehiscence
      at the umbilical port site. CONCLUSIONS: TLDG for distal EGC is a technically
      feasible and safe procedure when performed by a surgeon with sufficient
      experience in laparoscopic gastrectomy and might provide the benefits of reduced
      operating time and intraoperative blood lossand shorter convalescence compared
      with LADG.

PMID- 25061538
TI  - Does the retrieval of at least 15 lymph nodes confer an improved survival in
      patients with advanced gastric cancer?
AB  - PURPOSE: The standard surgical procedure recommended to treat gastric cancer in
      advanced cases is dissection of D2 lymph nodes (LNs). However, the optimum number
      of LNs that should be retrieved in advanced gastric cancer (AGC) remains
      debatable. Therefore, this study aimed to investigate the optimum number of
      retrieved LNs and determine the clinical implications of retrieved LN numbers on
      the treatment of AGC. MATERIALS AND METHODS: Of 575 AGC patients reviewed, 369
      who underwent open curative gastrectomy with D2 or more extensive LN dissection
      at our institution were analyzed according to their clinicopathologic
      characteristics and number of LNs retrieved. RESULTS: Multivariate regression
      analysis revealed that tumor size (P=0.006), depth of invasion (P=0.000), LN
      metastasis (P=0.000), and stage (P=0.000) were independent variables with
      predictive value. The 5-year survival rates were differed significantly according
      to the numbers of LNs retrieved ([1] 15~25 vs. >25 and [2] 15~39 vs. >=40) in
      patients with differentiated carcinoma. CONCLUSIONS: Tumor size, depth of
      invasion, LN metastasis, and stage were independent predictive factors for
      survival. The number of retrieved LNs was significantly associated with a long
      term survival benefit in patients with differentiated carcinoma. Therefore, our
      data suggest that the retrieval of a minimum of 15 LNs may not be sufficient to
      warrant a recommendation for further curative surgery and that extensive LN
      dissection should be considered in advanced carcinoma of the differentiated type.

PMID- 25061539
TI  - Initial clinical experience with cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy in signet-ring cell gastric cancer with peritoneal
      metastases.
AB  - PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) have been shown to improve survival in select patients with
      gastric cancer and peritoneal metastases. It remains unclear, however, whether
      this multimodal treatment protocol is also beneficial for signet-ring cell
      gastric cancer (SRC) patients with peritoneal metastases. MATERIALS AND METHODS:
      Clinical data of patients scheduled for upfront systemic chemotherapy consisting
      of 5-FU (2,600 mg/m(2)), folinic acid (200 mg/m(2)), docetaxel (50 mg/m(2)), and
      oxaliplatin (85 mg/m(2)) followed by CRS and HIPEC using cisplatin (50 mg/m(2))
      at the Comprehensive Cancer Center, University Hospital Tubingen, Germany were
      retrospectively analyzed. RESULTS: Eighteen consecutive patients for whom
      irresectability has been ruled out by a computed tomography scan were enrolled.
      However, complete cytoreduction could only be achieved in 72% of patients. When
      categorizing patients with respect to the completeness of cytoreduction, we found
      no difference between both groups considering tumor- or patient-related factors.
      The overall complication rate following complete cytoreduction and HIPEC was 46%.
      Within a median follow-up of 6.6 (0.5~31) months, the median survival for CRS and
      HIPEC patients was 8.9 months as opposed to 1.1 months for patients where
      complete cytoreduction could not be achieved. Following complete cytoreduction
      and HIPEC, progression-free survival was 6.2 months. CONCLUSIONS: In SRC with
      peritoneal metastases, the prognosis appears to remain poor irrespective of
      complete CRS and HIPEC. Moreover, complete cytoreduction could not be achieved in
      a considerable percentage of patients. In SRC, CRS and HIPEC should be restricted
      to highly selective patients in order to avoid exploratory laparotomy.

PMID- 25061536
TI  - Clinical practice guidelines for gastric cancer in Korea: an evidence-based
      approach.
AB  - Although gastric cancer is quite common in Korea, the treatment outcome is
      relatively favorable compared to those in western countries. However, there are
      currently no Korean multidisciplinary guidelines for gastric cancer. Experts from
      related societies developed guidelines de novo to meet Korean circumstances and
      requirements, including 23 recommendation statements for diagnosis (n=9) and
      treatment (n=14) based on relevant key questions. The quality of the evidence was
      rated according to the GRADE evidence evaluation framework: the evidence levels
      were based on a systematic review of the literature, and the recommendation
      grades were classified as either strong or weak. The applicability of the
      guidelines was considered to meet patients' view and preferences in the context
      of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy,
      endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery,
      therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic
      evaluation. An external review of the guidelines was conducted during the
      finalization phase. 

PMID- 25061540
TI  - At which stage of gastric cancer progression do levels of carcinoembryonic
      antigen and carbohydrate antigen 19-9 increase? Application in advanced gastric
      cancer treatment.
AB  - PURPOSE: Since there are no proven tumor markers that reflect the course of
      gastric cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9
      (CA19-9) are commonly used alternatives. However, the degree of progression that
      corresponds to an increase in these markers, and the values of these markers at
      different cancer stages, remains unclear. MATERIALS AND METHODS: This study
      enrolled 1,733 gastric cancer patients who underwent surgery and whose pre
      operative CEA and CA19-9 levels were known. Survival curves and mean values of
      the two markers were compared according to the degree of cancer progression:
      serosa-unexposed (SU), serosa-exposed (SE), direct invasion (DI), localized
      seeding (P1), and extensive seeding (P2). RESULTS: The 5-year overall survival
      rates at each stage differed significantly, except between DI and P1 patients
      (17.1% vs. 10.5%, P=0.344). The mean CEA values in SU, SE, DI, P1, and P2
      patients were 5.80, 5.48, 13.36, 8.06, and 22.82, respectively. The CA19-9 values
      for these patients were 49.40, 38.97, 101.67, 73.77, and 98.57, respectively. The
      increase in CEA in P2 patients was statistically significant (P=0.002), and the
      increases in CA19-9 in DI and P2 patients were significant (P=0.025, 0.007,
      respectively). There was a fair correlation between the two markers in P2
      patients (r=0.494, P<0.001). CONCLUSIONS: CA19-9 can be used to assess DI of
      gastric cancer into adjacent organs. Both markers are useful for predicting the
      presence of extensive peritoneal seeding.

PMID- 25061541
TI  - Effects of screening on gastric cancer management: comparative analysis of the
      results in 2006 and in 2011.
AB  - PURPOSE: This study aimed to analyze the effect of screening by using endoscopy
      on the diagnosis and treatment of gastric cancer. MATERIALS AND METHODS: The
      clinicopathologic characteristics of gastric cancer were compared in individuals
      who underwent an endoscopy because of symptoms (non-screening group) or for
      screening purposes (screening group). The distributions of gastric cancer stages
      and treatment modalities in 2006 and 2011 were compared. RESULTS: The proportion
      of patients in the screening group increased from 45.1% in 2006 to 65.4% in 2011
      (P<0.001). The proportion of stage I cancers in the entire patient sample also
      increased (from 60.5% in 2006 to 70.6% in 2011; P=0.029). In 2011, the
      percentages of patients with cancer stages I, II, III, and IV were 79.9%, 8.2%,
      10.9%, and 1.1%, respectively, in the screening group, and 47.9%, 10.8%, 29.8%,
      and 11.5%, respectively, in the non-screening group. The proportion of
      laparoscopic and robotic surgeries increased from 9.6% in 2006 to 48.3% in 2011
      (P<0.001), and endoscopic submucosal dissection increased from 9.8% in 2006 to
      19.1% 2011 (P<0.001). CONCLUSIONS: The proportion of patients diagnosed with
      gastric cancer by using the screening program increased between 2006 and 2011.
      This increase was associated with a high proportion of early-stage cancer
      diagnoses and increased use of minimally invasive treatments.

PMID- 25061542
TI  - Gastric adenocarcinoma with prostatic metastasis.
AB  - Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare.
      Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with
      prostatic metastasis diagnosed through the analysis of biopsy specimens from
      representative lesions in the stomach and prostate gland. Immunohistochemistry of
      the prostatic tissue showed positive staining for cytokeratin 7 and negative
      staining for prostate-specific antigen (PSA), whereas the serum PSA level was
      normal, confirming the diagnosis of prostatic metastasis from carcinoma of the
      stomach. 

PMID- 25061543
TI  - Gastric metastasis from ovarian cancer presenting as a submucosal tumor: a case
      report.
AB  - Gastric metastasis from ovarian cancer is rarely reported worldwide. In Korea,
      only 2 such cases have been reported. Here we report a case of a 58-year-old
      woman with metastatic gastric cancer from an ovarian adenocarcinoma. Endoscopic
      examination showed that the cancer presented as a submucosal tumor without
      ulceration. A subsequent gastrectomy confirmed the diagnosis of metastatic
      ovarian serous adenocarcinoma. 

PMID- 25061544
TI  - Occult gastric cancer presenting as hypoxia from pulmonary tumor thrombotic
      microangiopathy.
AB  - Pulmonary tumor thrombotic microangiopathy (PTTM) causing fatal pulmonary
      hypertension is a rare presentation of malignancy. In general, patients with PTTM
      rapidly succumb to death due to severe hypoxia. To date, very few cases of PTTM
      have been reported in the literature; and most of these cases were from gastric
      cancer and were diagnosed on post mortem autopsy, as it is extremely challenging
      to make an ante mortem diagnosis. We here report on a case of undiagnosed diffuse
      gastric cancer, presenting as worsening hypoxia. The clinical, radiographic, and
      echocardiographic features, and laboratory and pathological results were
      consistent with PTTM from gastric cancer. The patient was started on
      anticoagulation therapy, corticosteroids, and high-flow oxygen. However, her
      hypoxia worsened to the extent that she required ventilator support, and she died
      soon after intubation due to cardiac arrest. Since diffuse gastric cancer is
      associated with hereditary diffuse gastric cancer syndrome, cadherin 1 gene
      mutation analysis was performed to estimate the risk to her daughters. The test
      came back negative. 

PMID- 25061545
TI  - A More Accurate Kinetic Monte Carlo Approach to a Monodimensional Surface
      Reaction: The Interaction of Oxygen with the RuO2(110) Surface.
AB  - The theoretical study of catalysis would substantialy benefit from the use of
      atomistic simulations that can provide information beyond mean-field approaches.
      To date, the nanoscale understanding of surface reactions has been only
      qualitatively achieved by means of kinetic Monte Carlo coupled to density
      functional theory, KMC-DFT. Here, we examine a widely employed model for oxygen
      interaction with the RuO2(110) surface, a highly anisotropic system. Our analysis
      reveals several covert problems that render as questionable the model's
      predictions. We suggest an advanced approach that considers all the relevant
      elementary steps and configurations while smoothing the intrinsic errors in the
      DFT description of oxygen. Under these conditions, KMC provides quantitative
      agreement to temperature-programmed desorption experiments. These results
      illustrate how KMC-based simulations can be pushed forward so that they evolve
      toward being the standard methodology to study complex chemistry at the
      nanoscale.

PMID- 25061546
TI  - Combinations of immunostimulatory antibodies with synergistic effects against
      spontaneous cancer.
AB  - Immunostimulatory monoclonal antibodies can be given in combinations, hence
      modulating the activity of 2 or more receptors of the immune system. Some of
      these combinations have been shown to synergize at the elicitation of
      therapeutically relevant immune responses in transgenic mice developing
      spontaneous, oncogene-driven tumors, including multifocal hepatocellular
      carcinomas expressing ovalbumin as a surrogate tumor-associated antigen.

PMID- 25061547
TI  - UTE MRI of the Osteochondral Junction.
AB  - The osteochondral junction is composed of numerous tissue components and serves
      important functions relating to structural stability and proper nutrition in
      joints such as the knee and spine. Conventional MR techniques have been
      inadequate at imaging the tissues of the osteochondral junction primarily because
      of the intrinsically short T2 nature of these tissues, rendering them "invisible"
      with the standard acquisitions. Ultrashort time to echo (UTE) MR techniques
      acquire sufficient MR signal of osteochondral tissues, thereby allowing direct
      evaluation. This article reviews the anatomy of the osteochondral junction of the
      knee and the spine, technical aspects of UTE MRI, and the application of UTE MRI
      for evaluation of the osteochondral junction.

PMID- 25061548
TI  - Instability of the Vertebrae Remains following Balloon Kyphoplasty.
AB  - Study Design Retrospective cohort study. Objectives The mechanism underlying the
      pain relief observed following balloon kyphoplasty (BKP) to vertebral compression
      fractures is reported to involve stabilization of the fractured vertebrae.
      However, whether fixation of the vertebrae was achieved immediately after BKP has
      not been investigated. The purpose of this study was to assess fixation of the
      vertebrae immediately after BKP and whether the instability was related to visual
      analog scale (VAS) scores. Methods Thirty-eight patients with vertebrae that were
      evaluated on lateral roentgenkymography within 1 week after BKP were recruited.
      Instability was defined as a cleft observed between the cement and end plate of
      the vertebra in the supine position that disappeared in the sitting position, and
      the posterior wall height of the vertebra was reduced in the sitting position.
      Results Instability of the vertebrae immediately after BKP was observed in 17
      cases. VAS scores improved in all cases, and no significant differences were
      observed with or without instability. Conclusions The mechanism of rapid pain
      relief following BKP was not strong fixation but some degree of stabilization or
      other factors. We suggest that more research is needed about the mechanism of
      pain relief following BKP in the future. 

PMID- 25061549
TI  - Multiple myeloma-associated amyloidoma of the sacrum: case report and review of
      the literature.
AB  - Study Design Case report. Objectives With only two previously reported cases,
      localized amyloidosis of the sacrum is extremely rare. Here we report a 64-year
      old woman with a large osteolytic lesion accompanied by weakness and paresthesia
      of the right leg and difficulties in bladder control. Methods Fine needle biopsy
      and standard staging procedures revealed a primary solitary amyloidoma that was
      treated with intralesional resection, lumbopelvic stabilization, and
      consolidation radiotherapy. Results Clinical follow-up revealed the diagnosis of
      multiple myeloma 9 months after initial treatment. At 12 months, no local
      recurrence has occurred, the neurologic symptoms have resolved, and the systemic
      disease is in remission. Conclusions Intralesional resection with adjuvant
      radiotherapy of the amyloidoma achieved good local tumor control with limited
      morbidity. 

PMID- 25061550
TI  - Study of analytical method to seek for exact solutions of variant Boussinesq
      equations.
AB  - ABSTRACT: In this paper, we have been acquired the soliton solutions of the
      Variant Boussinesq equations. Primarily, we have used the enhanced (G'/G)
      expansion method to find exact solutions of Variant Boussinesq equations. Then,
      we attain some exact solutions including soliton solutions, hyperbolic and
      trigonometric function solutions of this equation. MATHEMATICS SUBJECT
      CLASSIFICATION: 35 K99; 35P05; 35P99.

PMID- 25061551
TI  - Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium,
      antimony, selenium and lead in the equine liver and kidneys.
AB  - The concentrations of specific elements in the equine liver and kidneys are of
      practical relevance since horses are not only food-producing animals, but also
      partially serve as an indicator for the environmental pollution, as the basic
      feed includes plants like grass, grain and fruits. In this study, the
      concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc
      (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se) and lead (Pb)
      were measured in the liver, renal cortex and renal medulla of 21 horses (8 male;
      13 female; aged between 5 months-28 years), using inductively coupled plasma mass
      spectrometry. Comparable Cu and Zn concentrations were detected in the liver and
      renal cortex, while approximately 50% lower concentrations were measured in the
      renal medulla. The lowest Sr, Cd and Se, but the highest Mn, Sb and Pb
      concentrations were measured in the liver. The Ba concentrations were comparable
      in the renal cortex and medulla, but lower in the liver of the horses. Gender
      related differences were observed for Cd, Mn and Cr, with higher Cd
      concentrations in the liver, but lower Mn concentrations in the renal cortex and
      lower Cr concentrations in the renal medulla of female horses. Age-related
      differences were detected for most measured elements, however, the animal number
      per age-group was only low. In conclusion, the present study provides important
      reference data for the storage of Sr, Ba, Cd, Cu, Zn, Mn, Cr, Sb, Se and Pb in
      the liver and kidneys of horses, which are of practical relevance for an
      evaluation of the exposure of horses to these elements, either via feed or the
      environment. 

PMID- 25061552
TI  - Predictors for mortality in hospitalized patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been the only
      leading cause of death associated with a continuously increasing trend in the US
      over the past 30 years. OBJECTIVES: The aim of this research was to identify
      predictors for all-cause in-hospital mortality for COPD patients. METHODS: We
      conducted a cross-sectional study of patients with the discharge diagnosis of
      COPD, utilizing the 2007 Premier Perspective database. Inpatients aged 40 years
      and above were selected if they had a discharge with a primary diagnosis of COPD
      between January 1, 2007 and December 31, 2007. All data analyses were based on
      individual level. If a patient had multiple discharges, only the last discharge
      was included for mortality analysis. Predictors for mortality were identified by
      multiple logistic regressions. Bonferroni correction for multiple logistic
      regression models was adapted to control for family-wise errors. RESULTS: The
      total of 57,224 patients was selected for data analysis in the study. All-cause
      in-hospital mortality for patients with COPD was 2.4%. Older age, insurance
      coverage, elective admission, intensive care unit admission, prolonged length of
      stay, increased Deyo-adapted Charlson Index (DCI) score and Elixhauser
      comorbidities of renal failure, metastatic cancer, solid tumor without
      metastasis, and weight loss were identified as independent predictors for all
      cause in-hospital mortality. Antibiotics and beta-blockers were predictors of
      lower all-cause in-hospital mortality risk after adjusting for other factors.
      CONCLUSIONS: The nationwide discharge database provides useful information to
      identify predictors for all-cause in-hospital mortality of patients with COPD.

PMID- 25061553
TI  - Intraocular lens implantation in unilateral congenital cataract with minimal
      levels of persistent fetal vasculature in the first 18 months of life.
AB  - PURPOSE: To describe the incidence of unilateral congenital cataract associated
      with minimal (ultrasonically undetectable) levels of persistent fetal vasculature
      in the first 18 months of the life and to report surgical methods for intraocular
      lens implantation, using 25-gauge vitrectomy system. METHODS: Retrospective
      review was made on 16 consecutive patients with bilateral or unilateral
      congenital cataract in the first 18 months of the life who underwent surgery at
      Okayama University Hospital after the introduction of the 25-gauge vitrectomy
      system from October 2005 to March 2013. As the standard of care at this hospital
      in the study period, intraocular lenses were not implanted in children with
      bilateral cataract while intraocular lenses were implanted in those with
      unilateral cataract. RESULTS: Ten children with bilateral cataract underwent
      lensectomy in both eyes with a 25-gauge vitreous cutter under irrigation with a
      25-gauge infusion cannula, inserted from two side ports at the corneal limbus.
      Six children with unilateral cataract underwent intraocular lens implantation and
      posterior capsulotomy after lens aspiration from limbal side ports. No patient
      showed vitreous abnormalities on ultrasound examinations before the surgery. At
      the surgery, all 10 children with bilateral cataract showed no additional
      abnormalities. In contrast, 3 children with unilateral cataract at the age
      younger than 12 months showed white fibrous tissue in the anterior vitreous
      integrated with the posterior lens capsule while the other 3 children with
      unilateral cataract at the age from 12 to 18 months did not have vitreous
      abnormalities. The fibrous tissue was cut together in the process of posterior
      capsulotomy from a 25-gauge trocar inserted at 1.5 mm posterior from the corneal
      limbus. CONCLUSIONS: Unilateral congenital cataract in the first 12 months of the
      life has a high incidence for the association with anterior type of persistent
      fetal vasculature which could not be detected by preoperative ultrasound
      examinations. Intraocular lens implantation was technically feasible in
      unilateral cataract with or without minimal levels of persistent fetal
      vasculature in the first 18 months of the life.

PMID- 25061555
TI  - Human obesity: FTO, IRX3, or both?

PMID- 25061554
TI  - Systematic analysis of transcription-level effects of neurodegenerative diseases
      on human brain metabolism by a newly reconstructed brain-specific metabolic
      network.
AB  - Network-oriented analysis is essential to identify those parts of a cell affected
      by a given perturbation. The effect of neurodegenerative perturbations in the
      form of diseases of brain metabolism was investigated by using a newly
      reconstructed brain-specific metabolic network. The developed stoichiometric
      model correctly represents healthy brain metabolism, and includes 630 metabolic
      reactions in and between astrocytes and neurons, which are controlled by 570
      genes. The integration of transcriptome data of six neurodegenerative diseases
      (Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic
      lateral sclerosis, multiple sclerosis, schizophrenia) with the model was
      performed to identify reporter features specific and common for these diseases,
      which revealed metabolites and pathways around which the most significant changes
      occur. The identified metabolites are potential biomarkers for the pathology of
      the related diseases. Our model indicated perturbations in oxidative stress,
      energy metabolism including TCA cycle and lipid metabolism as well as several
      amino acid related pathways, in agreement with the role of these pathways in the
      studied diseases. The computational prediction of transcription factors that
      commonly regulate the reporter metabolites was achieved through binding-site
      analysis. Literature support for the identified transcription factors such as
      USF1, SP1 and those from FOX families are known from the literature to have
      regulatory roles in the identified reporter metabolic pathways as well as in the
      neurodegenerative diseases. In essence, the reconstructed brain model enables the
      elucidation of effects of a perturbation on brain metabolism and the illumination
      of possible machineries in which a specific metabolite or pathway acts as a
      regulatory spot for cellular reorganization. 

PMID- 25061556
TI  - Inactivation of the cardiomyocyte glucagon-like peptide-1 receptor (GLP-1R)
      unmasks cardiomyocyte-independent GLP-1R-mediated cardioprotection.
AB  - GLP-1R agonists improve outcomes in ischemic heart disease. Here we studied GLP
      1R-dependent adaptive and cardioprotective responses to ventricular injury. Glp1r
      (-/-) hearts exhibited chamber-specific differences in gene expression, but
      normal mortality and left ventricular (LV) remodeling after myocardial infarction
      (MI) or experimental doxorubicin-induced cardiomyopathy. Selective disruption of
      the cardiomyocyte GLP-1R in Glp1r (CM-/-) mice produced no differences in
      survival or LV remodeling following LAD coronary artery occlusion. Unexpectedly,
      the GLP-1R agonist liraglutide still produced robust cardioprotection and
      increased survival in Glp1r (CM-/-) mice following LAD coronary artery occlusion.
      Although liraglutide increased heart rate (HR) in Glp1r (CM-/-) mice, basal HR
      was significantly lower in Glp1r (CM-/-) mice. Hence, endogenous cardiomyocyte
      GLP-1R activity is not required for adaptive responses to ischemic or
      cardiomyopathic injury, and is dispensable for GLP-1R agonist-induced
      cardioprotection or enhanced chronotropic activity. However the cardiomyocyte GLP
      1R is essential for the control of HR in mice. 

PMID- 25061557
TI  - PTBP1 is required for glucose-stimulated cap-independent translation of insulin
      granule proteins and Coxsackieviruses in beta cells.
AB  - Glucose and GLP-1 stimulate not only insulin secretion, but also the post
      transcriptional induction of insulin granule biogenesis. This process involves
      the nucleocytoplasmic translocation of the RNA binding protein PTBP1. Binding of
      PTBP1 to the 3'-UTRs of mRNAs for insulin and other cargoes of beta cell granules
      increases their stability. Here we show that glucose enhances also the binding of
      PTBP1 to the 5'-UTRs of these transcripts, which display IRES activity, and their
      translation exclusively in a cap-independent fashion. Accordingly, glucose
      induced biosynthesis of granule cargoes was unaffected by pharmacological,
      genetic or Coxsackievirus-mediated inhibition of cap-dependent translation.
      Infection with Coxsackieviruses, which also depend on PTBP1 for their own cap
      independent translation, reduced instead granule stores and insulin release.
      These findings provide insight into the mechanism for glucose-induction of
      insulin granule production and on how Coxsackieviruses, which have been
      implicated in the pathogenesis of type 1 diabetes, can foster beta cell failure. 

PMID- 25061558
TI  - A link between hepatic glucose production and peripheral energy metabolism via
      hepatokines.
AB  - Type 2 diabetes is characterized by a deterioration of glucose tolerance, which
      associates insulin resistance of glucose uptake by peripheral tissues and
      increased endogenous glucose production. Here we report that the specific
      suppression of hepatic glucose production positively modulates whole-body glucose
      and energy metabolism. We used mice deficient in liver glucose-6 phosphatase that
      is mandatory for endogenous glucose production. When they were fed a high
      fat/high sucrose diet, they resisted the development of diabetes and obesity due
      to the activation of peripheral glucose metabolism and thermogenesis. This was
      linked to the secretion of hepatic hormones like fibroblast growth factor 21 and
      angiopoietin-like factor 6. Interestingly, the deletion of hepatic glucose-6
      phosphatase in previously obese and insulin-resistant mice resulted in the rapid
      restoration of glucose and body weight controls. Therefore, hepatic glucose
      production is an essential lever for the control of whole-body energy metabolism
      during the development of obesity and diabetes. 

PMID- 25061559
TI  - ER calcium release promotes mitochondrial dysfunction and hepatic cell
      lipotoxicity in response to palmitate overload.
AB  - Palmitate overload induces hepatic cell dysfunction characterized by enhanced
      apoptosis and altered citric acid cycle (CAC) metabolism; however, the mechanism
      of how this occurs is incompletely understood. We hypothesize that elevated doses
      of palmitate disrupt intracellular calcium homeostasis resulting in a net flux of
      calcium from the ER to mitochondria, activating aberrant oxidative metabolism. We
      treated primary hepatocytes and H4IIEC3 cells with palmitate and calcium
      chelators to identify the roles of intracellular calcium flux in lipotoxicity. We
      then applied (13)C metabolic flux analysis (MFA) to determine the impact of
      calcium in promoting palmitate-stimulated mitochondrial alterations. Co-treatment
      with the calcium-specific chelator BAPTA resulted in a suppression of markers for
      apoptosis and oxygen consumption. Additionally, (13)C MFA revealed that BAPTA co
      treated cells had reduced CAC fluxes compared to cells treated with palmitate
      alone. Our results demonstrate that palmitate-induced lipoapoptosis is dependent
      on calcium-stimulated mitochondrial activation, which induces oxidative stress. 

PMID- 25061560
TI  - 11beta-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by
      modulating fatty acid transport protein-5 in the liver of mice.
AB  - 11beta-Hydroxysteroid dehydrogenase-1 (11beta-HSD1) plays a key role in
      glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols
      and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of
      impaired 11beta-HSD1 activity remained unknown. We profiled plasma and liver BAs
      in liver-specific and global 11beta-HSD1-deficient mice. 11beta-HSD1-deficiency
      resulted in elevated circulating unconjugated BAs, an effect more pronounced in
      global than liver-specific knockout mice. Gene expression analyses revealed
      decreased expression of the BA-CoA ligase Fatp5, suggesting impaired BA
      amidation. Reduced organic anion-transporting polypeptide-1A1 (Oatp1a1) and
      enhanced organic solute-transporter-beta (Ostb) mRNA expression were observed in
      livers from global 11beta-HSD1-deficient mice. The impact of 11beta-HSD1
      deficiency on BA homeostasis seems to be GR-independent because intrahepatic
      corticosterone and GR target gene expression were not substantially decreased in
      livers from global knockout mice. Moreover, Fatp5 expression in livers from
      hepatocyte-specific GR knockout mice was unchanged. The results revealed a role
      for 11beta-HSD1 in BA homeostasis. 

PMID- 25061561
TI  - Methyl-donor supplementation in obese mice prevents the progression of NAFLD,
      activates AMPK and decreases acyl-carnitine levels.
AB  - Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic lipid
      accumulation and steatosis, and is closely linked to liver one-carbon (C1)
      metabolism. We assessed in C57BL6/N mice whether NAFLD induced by a high-fat (HF)
      diet over 8 weeks can be reversed by additional 4 weeks of a dietary methyl-donor
      supplementation (MDS). MDS in the obese mice failed to reverse NAFLD, but
      prevented the progression of hepatic steatosis associated with major changes in
      key hepatic C1-metabolites, e.g. S-adenosyl-methionine and S-adenosyl
      homocysteine. Increased phosphorylation of AMPK-alpha together with enhanced beta
      HAD activity suggested an increased flux through fatty acid oxidation pathways.
      This was supported by concomitantly decreased hepatic free fatty acid and acyl
      carnitines levels. Although HF diet changed the hepatic phospholipid pattern, MDS
      did not. Our findings suggest that dietary methyl-donors activate AMPK, a key
      enzyme in fatty acid beta-oxidation control, that mediates increased fatty acid
      utilization and thereby prevents further hepatic lipid accumulation. 

PMID- 25061562
TI  - Stress- and diet-induced fat gain is controlled by NPY in catecholaminergic
      neurons.
AB  - Neuropeptide Y (NPY) and noradrenaline are commonly co-expressed in sympathetic
      neurons. Both are key regulators of energy homeostasis and critical for stress
      coping. However, little is known about the specific function of NPY in the
      catecholaminergic system in these regulations. Here we show that mice with NPY
      expression only in the noradrenergic and adrenergic cells of the
      catecholaminergic system (catNPY) exhibited exacerbated diet-induced obesity,
      lower body and brown adipose tissue temperatures compared to WT and NPY(-/-) mice
      under a HFD. Furthermore, chronic stress increased adiposity and serum
      corticosterone level in WT but not NPY(-/-) mice. Re-introducing NPY specifically
      to the catecholaminergic system in catNPY mice restored stress responsiveness
      associated with increased respiratory exchange ratio and decreased liver pACC to
      tACC ratio. These results demonstrate catecholaminergic NPY signalling is
      critical in mediating diet- and chronic stress-induced fat gain via effects on
      diet-induced thermogenesis and stress-induced increases in corticosterone levels
      and lipogenic capacity. 

PMID- 25061563
TI  - Voxel-based gray and white matter morphometry correlates of hallucinations in
      schizophrenia: The superior temporal gyrus does not stand alone.
AB  - INTRODUCTION: Auditory verbal hallucinations (AVH) in schizophrenia (SZ) have
      been proposed to result from abnormal local, interregional and interhemispheric
      integration of brain signals in regions involved in language production and
      perception. This abnormal functional integration may find its base in
      morphological abnormalities. Structurally, AVHs have been frequently linked to
      abnormal morphology of the superior temporal gyrus (STG), but only a few studies
      investigated the relation of hallucination presence with both whole-brain gray
      matter (GM) and white matter (WM) morphometry. METHODS: Using a unified voxel
      based morphometry-DARTEL approach, we investigated correlates of AVH presence in
      51 schizophrenia patients (20 non-hallucinating [SZ -], 31 hallucinating [SZ +]),
      and included 51 age and sex matched healthy participants. Effects are reported at
      p < .05 FWE corrected. RESULTS: Patients showed lower GM volume of the left STG
      than controls, irrespective of AVH presence. In addition, SZ + showed lower GM
      volume of the left inferior frontal and right parahippocampal gyrus, and higher
      WM volume of the left postcentral and superior parietal lobule than controls.
      Finally, volume of the putamen was lower in SZ + compared to SZ -. No effects on
      corpus callosum morphometry were observed. Delusion severity, general positive
      and negative symptomatology illness duration, and medication status could not
      explain the results. DISCUSSION: Results suggest that STG GM abnormalities
      underlie the general susceptibility to experience psychotic symptoms and that
      additional abnormalities in a network of medial temporal, ventrolateral,
      putaminal, and parietal regions related to verbal memory and speech production
      may specifically increase the likelihood of experiencing AVH. Future studies
      should clarify the meaning of morphometry abnormalities for functional
      interregional communication.

PMID- 25061564
TI  - Visual and proprioceptive interaction in patients with bilateral vestibular loss.
AB  - Following bilateral vestibular loss (BVL) patients gradually adapt to the loss of
      vestibular input and rely more on other sensory inputs. Here we examine changes
      in the way proprioceptive and visual inputs interact. We used functional magnetic
      resonance imaging (fMRI) to investigate visual responses in the context of
      varying levels of proprioceptive input in 12 BVL subjects and 15 normal controls.
      A novel metal-free vibrator was developed to allow vibrotactile neck
      proprioceptive input to be delivered in the MRI system. A high level (100 Hz) and
      low level (30 Hz) control stimulus was applied over the left splenius capitis;
      only the high frequency stimulus generates a significant proprioceptive stimulus.
      The neck stimulus was applied in combination with static and moving (optokinetic)
      visual stimuli, in a factorial fMRI experimental design. We found that high level
      neck proprioceptive input had more cortical effect on brain activity in the BVL
      patients. This included a reduction in visual motion responses during high levels
      of proprioceptive input and differential activation in the midline cerebellum. In
      early visual cortical areas, the effect of high proprioceptive input was present
      for both visual conditions but in lateral visual areas, including V5/MT, the
      effect was only seen in the context of visual motion stimulation. The finding of
      a cortical visuo-proprioceptive interaction in BVL patients is consistent with
      behavioural data indicating that, in BVL patients, neck afferents partly replace
      vestibular input during the CNS-mediated compensatory process. An fMRI cervico
      visual interaction may thus substitute the known visuo-vestibular interaction
      reported in normal subject fMRI studies. The results provide evidence for a
      cortical mechanism of adaptation to vestibular failure, in the form of an
      enhanced proprioceptive influence on visual processing. The results may provide
      the basis for a cortical mechanism involved in proprioceptive substitution of
      vestibular function in BVL patients. 

PMID- 25061565
TI  - Neuroimaging after mild traumatic brain injury: review and meta-analysis.
AB  - This paper broadly reviews the study of mild traumatic brain injury (mTBI),
      across the spectrum of neuroimaging modalities. Among the range of imaging
      methods, however, magnetic resonance imaging (MRI) is unique in its applicability
      to studying both structure and function. Thus we additionally performed meta
      analyses of MRI results to examine 1) the issue of anatomical variability and
      consistency for functional MRI (fMRI) findings, 2) the analogous issue of
      anatomical consistency for white-matter findings, and 3) the importance of
      accounting for the time post injury in diffusion weighted imaging reports. As we
      discuss, the human neuroimaging literature consists of both small and large
      studies spanning acute to chronic time points that have examined both structural
      and functional changes with mTBI, using virtually every available medical imaging
      modality. Two key commonalities have been used across the majority of imaging
      studies. The first is the comparison between mTBI and control populations. The
      second is the attempt to link imaging results with neuropsychological
      assessments. Our fMRI meta-analysis demonstrates a frontal vulnerability to mTBI,
      demonstrated by decreased signal in prefrontal cortex compared to controls. This
      vulnerability is further highlighted by examining the frequency of reported mTBI
      white matter anisotropy, in which we show a strong anterior-to-posterior gradient
      (with anterior regions being more frequently reported in mTBI). Our final DTI
      meta-analysis examines a debated topic arising from inconsistent anisotropy
      findings across studies. Our results support the hypothesis that acute mTBI is
      associated with elevated anisotropy values and chronic mTBI complaints are
      correlated with depressed anisotropy. Thus, this review and set of meta-analyses
      demonstrate several important points about the ongoing use of neuroimaging to
      understand the functional and structural changes that occur throughout the time
      course of mTBI recovery. Based on the complexity of mTBI, however, much more work
      in this area is required to characterize injury mechanisms and recovery factors
      and to achieve clinically-relevant capabilities for diagnosis. 

PMID- 25061566
TI  - Automated cerebellar segmentation: Validation and application to detect smaller
      volumes in children prenatally exposed to alcohol.
AB  - OBJECTIVE: To validate an automated cerebellar segmentation method based on
      active shape and appearance modeling and then segment the cerebellum on images
      acquired from adolescents with histories of prenatal alcohol exposure (PAE) and
      non-exposed controls (NC). METHODS: Automated segmentations of the total
      cerebellum, right and left cerebellar hemispheres, and three vermal lobes
      (anterior, lobules I-V; superior posterior, lobules VI-VII; inferior posterior,
      lobules VIII-X) were compared to expert manual labelings on 20 subjects, studied
      twice, that were not used for model training. The method was also used to segment
      the cerebellum on 11 PAE and 9 NC adolescents. RESULTS: The test-retest
      intraclass correlation coefficients (ICCs) of the automated method were greater
      than 0.94 for all cerebellar volume and mid-sagittal vermal area measures,
      comparable or better than the test-retest ICCs for manual measurement (all ICCs >
      0.92). The ICCs computed on all four cerebellar measurements (manual and
      automated measures on the repeat scans) to compare comparability were above 0.97
      for non-vermis parcels, and above 0.89 for vermis parcels. When applied to
      patients, the automated method detected smaller cerebellar volumes and mid
      sagittal areas in the PAE group compared to controls (p < 0.05 for all regions
      except the superior posterior lobe, consistent with prior studies). DISCUSSION:
      These results demonstrate excellent reliability and validity of automated
      cerebellar volume and mid-sagittal area measurements, compared to manual
      measurements. These data also illustrate that this new technology for
      automatically delineating the cerebellum leads to conclusions regarding the
      effects of prenatal alcohol exposure on the cerebellum consistent with prior
      studies that used labor intensive manual delineation, even with a very small
      sample.

PMID- 25061567
TI  - MRI texture heterogeneity in the optic nerve predicts visual recovery after acute
      optic neuritis.
AB  - PURPOSE: To test the feasibility of using multi-scale MRI texture analysis to
      assess optic nerve pathology and to investigate how visual recovery relates to
      the severity of acute tissue damage in the optic nerve in patients after optic
      neuritis (ON). MATERIALS AND METHODS: We recruited 25 patients with acute ON.
      Retinal nerve fiber layer (RNFL) thickness; MRI lesion length and enhancement;
      optic nerve area ratio; and multi-scale MRI texture analysis, a measure of
      structural integrity, were used to assess tissue damage at baseline, and at 6 and
      12 months. The recovery in vision was defined as the functional outcome. Eight
      healthy subjects were imaged for control. RESULTS: We identified 25 lesions in
      the affected eyes (9 enhanced) and 5 in the clinically non-affected eyes (none
      enhanced). At baseline, we found that RNFL values were 20% thicker and lesion
      texture 14% more heterogeneous in the affected eyes than in the non-affected
      eyes, and lesion texture ratio of affected to non-affected eyes was greater in
      patients than in controls. In the affected eyes, visual acuity recovered
      significantly over 6 (18/23 patients) and 12 months (18/21 patients) when RNFL
      thickness and optic nerve area ratio decreased over time. Texture heterogeneity
      in the standard MRI of acute optic nerve lesions was the only measure that
      predicted functional recovery after ON. CONCLUSIONS: Tissue heterogeneity may be
      a potential measure of functional outcome in ON patients and advanced analysis of
      the texture in standard MRI could provide insights into mechanisms of injury and
      recovery in patients with similar disorders.

PMID- 25061568
TI  - General and specific effects of early-life psychosocial adversities on adolescent
      grey matter volume.
AB  - Exposure to childhood adversities (CA) is associated with subsequent alterations
      in regional brain grey matter volume (GMV). Prior studies have focused mainly on
      severe neglect and maltreatment. The aim of this study was to determine in
      currently healthy adolescents if exposure to more common forms of CA results in
      reduced GMV. Effects on brain structure were investigated using voxel-based
      morphometry in a cross-sectional study of youth recruited from a population-based
      longitudinal cohort. 58 participants (mean age = 18.4) with (n = 27) or without
      (n = 31) CA exposure measured retrospectively from maternal interview were
      included in the study. Measures of recent negative life events (RNLE) recorded at
      14 and 17 years, current depressive symptoms, gender, participant/parental
      psychiatric history, current family functioning perception and 5-HTTLPR genotype
      were covariates in analyses. A multivariate analysis of adversities demonstrated
      a general association with a widespread distributed neural network consisting of
      cortical midline, lateral frontal, temporal, limbic, and cerebellar regions.
      Univariate analyses showed more specific associations between adversity measures
      and regional GMV: CA specifically demonstrated reduced vermis GMV and past
      psychiatric history with reduced medial temporal lobe volume. In contrast RNLE
      aged 14 was associated with increased lateral cerebellar and anterior cingulate
      GMV. We conclude that exposure to moderate levels of childhood adversities
      occurring during childhood and early adolescence exerts effects on the developing
      adolescent brain. Reducing exposure to adverse social environments during early
      life may optimize typical brain development and reduce subsequent mental health
      risks in adult life. 

PMID- 25061569
TI  - Abeta and tau toxicities in Alzheimer's are linked via oxidative stress-induced
      p38 activation: protective role of vitamin E.
AB  - Oxidative stress is a hallmark of Alzheimer's disease (AD). We propose that
      rather than causing damage because of the action of free radicals, oxidative
      stress deranges signaling pathways leading to tau hyperphosphorylation, a
      hallmark of the disease. Indeed, incubation of neurons in culture with 5 uM beta
      amyloid peptide (Abeta) causes an activation of p38 MAPK (p38) that leads to tau
      hyperphosphorylation. Inhibition of p38 prevents Abeta-induced tau
      phosphorylation. Abeta-induced effects are prevented when neurons are co
      incubated with trolox (the water-soluble analog of vitamin E). We have confirmed
      these results in vivo, in APP/PS1 double transgenic mice of AD. We have found
      that APP/PS1 transgenic mice exhibit a high level of P-p38 in the hippocampus but
      not in cortex and this is prevented by feeding animals with a diet supplemented
      with vitamin E. Our results underpin the role of oxidative stress in the altered
      cell signaling in AD pathology and suggest that antioxidant prevention may be
      useful in AD therapeutics.

PMID- 25061571
TI  - Impact of Enzyme Replacement Therapy and Hematopoietic Stem Cell Therapy on
      Growth in Patients with Hunter Syndrome.
AB  - Patients with Hunter syndrome (mucopolysaccharidosis II) present with skeletal
      dysplasia including short stature as well as CNS and visceral organ involvement.
      A previous study on Hunter syndrome indicated an impact on brain and heart
      involvement after hematopoietic stem cell therapy (HSCT) at an early stage but
      little impact after enzyme replacement therapy (ERT) (Tanaka et al 2012).
      Meanwhile, impact on growth in patients with Hunter syndrome treated with ERT and
      HSCT has not been compared until now. We recently developed baseline growth
      charts for untreated patients with Hunter syndrome to evaluate the natural
      history of growth of these patients compared to unaffected controls (Patel et al,
      2014). To assess impact of ERT and HSCT on growth, clinical data were obtained
      from 44 Japanese male patients with MPS II; 26 patients had been treated with
      ERT, 12 patients had been treated with HSCT, and 6 had been treated with both ERT
      and HSCT. Height and weight were compared to untreated patients and unaffected
      controls from the previous study. We demonstrated 1) that MPS II patients, who
      had been treated with either ERT or HSCT, had increased height and weight when
      compared to untreated patients, and 2) that HSCT and ERT were equally effective
      in restoring growth of MPS II patients. In conclusion, HSCT should be considered
      as one of the primary therapeutic options for early stage treatment of MPS II, as
      HSCT has also been reported to have a positive effect on brain and heart valve
      development (Tanaka et al 2012).

PMID- 25061570
TI  - Formation of electrophilic oxidation products from mitochondrial cardiolipin in
      vitro and in vivo in the context of apoptosis and atherosclerosis.
AB  - Emerging evidence indicates that mitochondrial cardiolipins (CL) are prone to
      free radical oxidation and this process appears to be intimately associated with
      multiple biological functions of mitochondria. Our previous work demonstrated
      that a significant amount of potent lipid electrophiles including 4-hydroxy
      nonenal (4-HNE) was generated from CL oxidation through a novel chemical
      mechanism. Here we provide further evidence that a characteristic class of CL
      oxidation products, epoxyalcohol-aldehyde-CL (EAA-CL), is formed through this
      novel mechanism in isolated mice liver mitochondria when treated with the pro
      apoptotic protein t-Bid to induce cyt c release. Generation of these oxidation
      products are dose-dependently attenuated by a peroxidase inhibitor acetaminophen
      (ApAP). Using a mouse model of atherosclerosis, we detected significant amount of
      these CL oxidation products in liver tissue of low density lipoprotein receptor
      knockout (LDLR -/-) mice after Western diet feeding. Our studies highlight the
      importance of lipid electrophiles formation from CL oxidation in the settings of
      apoptosis and atherosclerosis as inhibition of CL oxidation and lipid
      electrophiles formation may have potential therapeutic value in diseases linked
      to oxidant stress and mitochondrial dysfunctions. 

PMID- 25061572
TI  - Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer.
AB  - PURPOSE: Survival outcome of locally advanced pancreatic cancer has been poor and
      little is known about prognostic factors of the disease, especially in locally
      advanced cases treated with concurrent chemoradiation. This study was to analyze
      overall survival and prognostic factors of patients treated with concurrent
      chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. MATERIALS AND
      METHODS: Medical records of 34 patients diagnosed with unresectable pancreatic
      cancer and treated with definitive CCRT, from December 2003 to December 2012,
      were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8
      Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. RESULTS: With a
      mean follow-up of 10 months (range, 0 to 49 months), median overall survival was
      9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median
      and mean time to progression were 5 and 7 months, respectively. Prognostic
      parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the
      Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose
      (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT
      CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant
      independent prognostic factors associated with improved overall survival (p <
      0.01 and p = 0.02, respectively). CONCLUSION: Overall treatment results in
      locally advanced pancreatic cancer are relatively poor and few improvements have
      been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and
      ECOG performance status 0 and 1 were significantly associated with an improved
      overall survival.

PMID- 25061573
TI  - The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal
      toxicity in locally advanced cervical cancer patients who were evaluated by
      rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.
AB  - PURPOSE: To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal
      point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT)
      and intracavitary brachytherapy (ICBT) in cervical cancer patients who were
      evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.
      MATERIALS AND METHODS: Retrospective study was designed for the patients with
      locally advanced cervical cancer, treated by radical radiotherapy from 2004 to
      2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and
      ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the
      association of toxicities. RESULTS: Thirty-nine patients were evaluated for late
      rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy.
      Grade 1 toxicities were the most common findings. According to endoscopic exam,
      the most common toxicities were congested mucosa (36 patients) and telangiectasia
      (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no
      association of cumulative rectal dose to rectal toxicity, except the association
      of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT
      SOMA) scale >= grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval,
      1.269-22.244). CONCLUSION: The cumulative rectal dose in EQD2 >65 Gy have
      association with >= grade 2 LENT-SOMA scale.

PMID- 25061575
TI  - Postoperative radiation therapy following the incomplete resection of a non-small
      cell lung cancer.
AB  - PURPOSE: To review the results of postoperative radiation therapy (PORT) for
      residual non-small cell lung cancer (NSCLC) following surgical resection and
      evaluate multiple clinicopathologic prognostic factors. MATERIALS AND METHODS: A
      total of 58 patients, who completed scheduled PORT for positive resection margin,
      among 658 patients treated with PORT from January 2001 to November 2011 were
      retrospectively analyzed. Radiation therapy was started at 4 to 6 weeks after
      surgery. Chemotherapy was also administered to 35 patients, either sequentially
      or concurrently with PORT. RESULTS: The median age of patients was 63 years
      (range, 40 to 82 years). The postoperative pathological stage I NSCLC was
      diagnosed in 10 (17.2%), stage II in 18 (31.0%), and stage III in 30 patients
      (51.7%). Squamous cell carcinoma was identified in 43, adenocarcinoma in 10,
      large cell in 1, others in 4 patients. Microscopic residual disease (R1) was
      diagnosed in 55 patients (94.8%), and the remaining three patients were diagnosed
      with gross residual disease (R2). The median dose of PORT was 59.4 Gy (range,
      50.0 to 64.8 Gy). Chemotherapy was administered to 35 patients (60%), and the
      median follow-up time was 22.0 months (range, 6.0 to 84.0 months). The 3-year
      locoregional relapse-free survival and distant metastasis-free survival rates
      were 82.1% and 52.9%, respectively. The median overall survival was 23.8 months
      (range, 6.0 to 84.1 months), and the 3-year overall survival rate was 58.2%.
      Chemotherapy did not influence the failure pattern or survival outcome.
      CONCLUSION: PORT is an effective modality for improving local tumor control in
      incompletely resected NSCLC patients. Major failure pattern was distant
      metastasis despite chemotherapy.

PMID- 25061574
TI  - Patterns of failure and prognostic factors in resected extrahepatic bile duct
      cancer: implication for adjuvant radiotherapy.
AB  - PURPOSE: To find the applicability of adjuvant radiotherapy for extrahepatic bile
      duct cancer (EBDC), we analyzed the pattern of failure and evaluate prognostic
      factors of locoregional failure after curative resection without adjuvant
      treatment. MATERIALS AND METHODS: In 97 patients with resected EBDC, the location
      of tumor was classified as proximal (n = 26) and distal (n = 71), using the
      junction of the cystic duct and common hepatic duct as the dividing point.
      Locoregional failure sites were categorized as follows: the hepatoduodenal
      ligament and tumor bed, the celiac artery and superior mesenteric artery, and
      other sites. RESULTS: The median follow-up time was 29 months for surviving
      patients. Three-year locoregional progression-free survival, progression-free
      survival, and overall survival rates were 50%, 42%, and 52%, respectively.
      Regarding initial failures, 79% and 81% were locoregional failures in proximal
      and distal EBDC patients, respectively. The most common site was the
      hepatoduodenal ligament and tumor bed. In the multivariate analysis, perineural
      invasion was associated with poor locoregional progression-free survival (p =
      0.023) and progression-free survival (p = 0.012); and elevated postoperative CA19
      9 (>=37 U/mL) did with poor locoregional progression-free survival (p = 0.002),
      progression-free survival (p < 0.001) and overall survival (p < 0.001).
      CONCLUSION: Both proximal and distal EBDC showed remarkable proportion of
      locoregional failure. Perineural invasion and elevated postoperative CA19-9 were
      risk factors of locoregional failure. In these patients with high risk of
      locoregional failure, adjuvant radiotherapy could be considered to improve
      locoregional control.

PMID- 25061576
TI  - Prognostic and predictive value of liver volume in colorectal cancer patients
      with unresectable liver metastases.
AB  - PURPOSE: To determine the prognostic and predictive value of liver volume in
      colorectal cancer patients with unresectable liver metastases. MATERIALS AND
      METHODS: Sixteen patients received whole liver radiotherapy (WLRT) between
      January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions.
      RESULTS: The median survival time after WLRT was 9 weeks. In univariate analysis,
      performance status, serum albumin and total bilirubin level, liver volume and
      extrahepatic metastases were associated with survival. The mean liver volume was
      significantly different between subgroups with and without pain relief (3,097 and
      4,739 mL, respectively; p = 0.002). CONCLUSION: A larger liver volume is a poor
      prognostic factor for survival and also a negative predictive factor for response
      to WLRT. If patients who are referred for WLRT have large liver volume, they
      should be informed of the poor prognosis and should be closely observed during
      and after WLRT.

PMID- 25061577
TI  - Cardiac dose reduction with breathing adapted radiotherapy using self respiration
      monitoring system for left-sided breast cancer.
AB  - PURPOSE: To quantify the cardiac dose reduction during breathing adapted
      radiotherapy using Real-time Position Management (RPM) system in the treatment of
      left-sided breast cancer. MATERIALS AND METHODS: Twenty-two patients with left
      sided breast cancer underwent CT scans during breathing maneuvers including free
      breathing (FB), deep inspiration breath-hold (DIBH), and end inspiration breath
      hold (EIBH). The RPM system was used to monitor respiratory motion, and the in
      house self respiration monitoring (SRM) system was used for visual feedback. For
      each scan, treatment plans were generated and dosimetric parameters from DIBH and
      EIBH plans were compared to those of FB plans. RESULTS: All patients completed CT
      scans with different breathing maneuvers. When compared with FB plans, DIBH plans
      demonstrated significant reductions in irradiated heart volume and the heart V25,
      with the relative reduction of 71% and 70%, respectively (p < 0.001). EIBH plans
      also resulted in significantly smaller irradiated heart volume and lower heart
      V25 than FB plans, with the relative reduction of 39% and 37%, respectively (p =
      0.002). Despite of significant expansion of lung volume using inspiration breath
      hold, there were no significant differences in left lung V25 among the three
      plans. CONCLUSION: In comparison with FB, both DIBH and EIBH plans demonstrated a
      significant reduction of radiation dose to the heart. In the training course, SRM
      system was useful and effective in terms of positional reproducibility and
      patient compliance.

PMID- 25061578
TI  - Aggressive clinical course of extramammary Paget disease after radiotherapy.
AB  - Extramammary Paget disease (EMPD) is a rare disease, especially in Asian
      populations. Surgical resection is considered the primary treatment option.
      Recently, radiotherapy has been suggested as an EMPD treatment, either as an
      alternative to surgical resection or in combination with surgical resection. This
      report reviewed a patient with EMPD who was treated with wide excision of the
      EMPD site followed by radiotherapy for remaining gross lymph node metastases. The
      aim of this report was to determine the optimal treatment for advanced EMPD. 

PMID- 25061579
TI  - Short-course hypofractionated radiochemotherapy for unresectable locally advanced
      cancer of the base of tongue: palliation only? A case report and short review of
      the literature.
AB  - We present a case of unresectable cancer of the base of tongue treated with
      hypofractionated 3D conformal radiotherapy and concomitant chemotherapy. Based on
      the excellent tumour response in this radiotherapy regimen and international
      experience in short course treatments we shortly reviewed, we propose that this
      therapeutic approach could be considered in a curative setting for patients
      unsuitable for the a standard long course radiochemotherapy schedule. 

PMID- 25061581
TI  - Is This Symptom Even a Food Allergy?: Clinical Types of Food Protein-induced
      Enterocolitis Syndrome.
AB  - Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized non
      IgE-mediated gastrointestinal food allergy. The diagnosis of FPIES is based on
      clinical history, sequential symptoms and the timing, after excluding other
      possible causes. It is definitively diagnosed by an oral food challenge test.
      Unfortunately, the diagnosis of FPIES is frequently delayed because of non
      specific symptoms and insufficient definitive diagnostic biomarkers. FPIES is not
      well recognized by clinicians; the affected infants are often mismanaged as
      having viral gastroenteritis, food poisoning, sepsis, or a surgical disease.
      Familiarity with the clinical features of FPIES and awareness of the indexes of
      suspicion for FPIES are important to diagnose FPIES. Understanding the recently
      defined clinical terms and types of FPIES is mandatory to suspect and correctly
      diagnose FPIES. The aim of this review is to provide a case-driven presentation
      as a guide of how to recognize the clinical features of FPIES to improve
      diagnosis and management of patients with FPIES. 

PMID- 25061580
TI  - Middle East Consensus Statement on the Prevention, Diagnosis, and Management of
      Cow's Milk Protein Allergy.
AB  - Presented are guidelines for the prevention, diagnosis, and treatment of cow's
      milk protein allergy (CMPA) which is the most common food allergy in infants. It
      manifests through a variety of symptoms that place a burden on both the infant
      and their caregivers. The guidelines were formulated by evaluation of existing
      evidence-based guidelines, literature evidence and expert clinical experience.
      The guidelines set out practical recommendations and include algorithms for the
      prevention and treatment of CMPA. For infants at risk of allergy, appropriate
      prevention diets are suggested. Breastfeeding is the best method for prevention;
      however, a partially hydrolyzed formula should be used in infants unable to be
      breastfed. In infants with suspected CMPA, guidelines are presented for the
      appropriate diagnostic workup and subsequent appropriate elimination diet for
      treatment. Exclusive breastfeeding and maternal dietary allergen avoidance are
      the best treatment. In infants not exclusively breastfed, an extensively
      hydrolyzed formula should be used with amino acid formula recommended if the
      symptoms are life-threatening or do not resolve after extensively hydrolyzed
      formula. Adherence to these guidelines should assist healthcare practitioners in
      optimizing their approach to the management of CMPA and decrease the burden on
      infants and their caregivers. 

PMID- 25061582
TI  - Clostridium difficile in Children: To Treat or Not to Treat?
AB  - Clostridium difficile infection has been increasing since 2000 in children and in
      adults. Frequent antibiotics use, comorbidity, and the development of
      hypervirulent strains have increased the risk of infection. Despite the high
      carriage rates of C. difficile, infants rarely develop clinical infection.
      Discontinuing antibiotics and supportive management usually leads to resolution
      of disease. Antibiotics use should be stratified depending on the patient's age
      and severity of the disease. 

PMID- 25061583
TI  - Dyslipidemia in children and adolescents: when and how to diagnose and treat?
AB  - Recently, the incidence and prevalence of obesity and dyslipidemia are
      increasing. Dyslipidemia is associated with significant comorbidities and
      complications, and with cardiovascular risk factors (obesity, diabetes mellitus,
      hypertension and smoking). The main objectives of this article are that describe
      the prevalence of dyslipidemia in Korean children and adolescents and review the
      diagnosis and management of dyslipidemia in children and adolescents. 

PMID- 25061584
TI  - Fundoplication in neonates and infants with primary gastroesophageal reflux.
AB  - PURPOSE: Gastroesophageal reflux in infant is a physiological process. However,
      surgery is performed in high risk infants with severe gastroesophageal reflux
      disease (GERD) when medical management fails. This study focuses on efficacy and
      safety of Nissen fundoplication for GERD in infants under age 12 months. METHODS:
      This study was a retrospective case analysis of 11 neonates and infants under 12
      months of age who underwent Nissen fundoplication following a failure of medical
      treatment between June 2010 and June 2013 at Pusan National University Children's
      Hospital. The records were reviewed to determine the effect of fundoplication on
      symptoms and post-operative complications. RESULTS: A total of 11 infants consist
      of four males and seven females. Mean birth weight was 2,305.5+/-558.6 g (1,390
      3,130 g). They had some underlying disease, which are not related with GERD such
      as congenital heart disease (54.5%), prematurity (45.5%), neurologic disease
      (18.2%), respiratory disease (18.2%), and other gastrointestinal disease. Mean
      body weight at surgery was 3,803.6+/-1,864.9 g (1,938.7-5,668.5 g). Mean age at
      operation was 99.9+/-107.6 days (17-276 days). Duration from operation to full
      enteral feeding was 10.9 days. Symptoms related GERD disappeared in all patients
      including one who got reoperation. One infant died of congenital heart disease
      unrelated to surgery. There were no complications related to fundoplication.
      CONCLUSION: Fundoplication is effective and safe treatment in the neonates and
      infants with severe GERD.

PMID- 25061585
TI  - Acalculous diffuse gallbladder wall thickening in children.
AB  - PURPOSE: Gallbladder (GB) wall thickening can be found in various conditions
      unrelated to intrinsic GB disease. We investigated the predisposing etiologies
      and the outcome of acalculous GB wall thickening in children. METHODS: We
      retrospectively analyzed 67 children with acalculous GB wall thickening who had
      visited our institute from June 2010 to June 2013. GB wall thickening was defined
      as a GB wall diameter >3.5 mm on abdominal ultrasound examination or computed
      tomography. Underlying diseases associated with GB wall thickening, treatment,
      and outcomes were studied. RESULTS: There were 36 boys and 31 girls (mean age,
      8.5+/-4.8 years [range, 7 months-16 years]). Systemic infection in 24 patients
      (35.8%), acute hepatitis in 18 (26.9%), systemic disease in 11 (16.4%),
      hemophagocytic lymphohistiocytosis in 4 (6.0%), acute pancreatitis in 3 (4.5%),
      and specific liver disease in 3 (4.5%) predisposed patients to GB wall
      thickening. Systemic infections were caused by bacteria in 10 patients (41.7%),
      viruses in 5 patients (20.8%), and fungi in 2 patients (8.3%). Systemic diseases
      observed were systemic lupus erythematosus in 2, drug-induced hypersensitivity in
      2, congestive heart failure in 2, renal disorder in 2. Sixty-one patients (91.0%)
      received symptomatic treatments or treatment for underlying diseases. Five
      patients (7.5%) died from underlying diseases. Cholecystectomy was performed in 3
      patients during treatment of the underlying disease. CONCLUSION: A wide range of
      extracholecystic conditions cause diffuse GB wall thickening that resolves
      spontaneously or with treatment of underlying diseases. Surgical treatments
      should be avoided if there are no definite clinical manifestations of
      cholecystitis.

PMID- 25061586
TI  - Growth and Tolerance Assessment of a Lutein-fortified Infant Formula.
AB  - PURPOSE: To evaluate safety, gastrointestinal tolerance, and growth of a new
      experimental starter formula (NESF) fortified with lutein, prebiotics,
      probiotics, nucleotides and beta-carotene, fed to infants within the first months
      of life. METHODS: This was a non-randomized, open, uncontrolled study conducted
      from December 2010 to May 2011. Twenty-three healthy infants aged 10 days to 2
      months old were enrolled. Outcomes included gastrointestinal tolerance, physical
      growth and safety. Prior to the initiation of the trial, the Scientific Research
      Institute of Nutrition of the Russian Academy of Medical Sciences confirmed that
      the NESF met all safety and nutritional parameters. RESULTS: NESF was well
      tolerated. The majority of infants fed this formula passed semi-liquid, yellow or
      yellow-brown. The mean stool frequency/day was 2.5+/-0.4 on study-day 14 and
      1.8+/-0.5 on study-day 28. The mean daily weight gain was 30.9+/-3.8 grams and
      the mean length gain during the 28 days of follow up was 3.1+/-0.8 cm,
      corresponding to the average physical growth normally seen in the first months of
      life in Russian infants. Six children left the study: one refused to drink the
      formula, one left the study as parents changed residence; and one child's parents
      have recalled their informed consent due to adverse event unrelated to the
      product. Three infants presented adverse events possibly related to the product
      (rash; colic and abdominal pain; constipation). Seventeen infants completed the
      trial. CONCLUSION: This study demonstrated that lutein-fortified formula is safe,
      well-tolerated and supported physical growth of evaluated infants.

PMID- 25061587
TI  - Duodenal perforation: unusual complication of gastrostomy tube replacement.
AB  - Feeding gastrostomy is widely used for children with feeding impairment. The
      replacement of gastrostomy tube is known as an easy and safe procedure. However,
      various complications associated with replacement of gastrostomy tube were
      reported, including fistula disruption and colo-cutaneous fistula. For
      replacement of gastrostomy tube in small children with small stomach, special
      cautions are needed. Here, we report a rare case of duodenal perforation as an
      acute complication after the replacement of gastrostomy tube for a 33-month-old
      girl. 

PMID- 25061588
TI  - Two Cases of Infantile Intra-abdominal Inflammatory Myofibroblastic Tumor.
AB  - Inflammatory myofibroblastic tumor (IMT) is rare mesenchymal solid tumor that
      consists of proliferating myofibroblasts with an inflammatory infiltrate
      background. It has a very low prevalence in infants and occurs mainly in children
      and young adults. IMT are mainly located in the thoracic cavity, but intra
      abdominal lesions are rare. IMT can exhibit locally aggressive neoplastic
      processes and metastases similar to malignancies, so, have clinical importance.
      Herein, we describe two infantile intra-abdominal IMT cases presenting with
      incidentally found palpable abdominal mass. A 4-month-old male infant had IMT at
      the ileal mesentery and a 5-month-old male infant had IMT at liver. Both cases
      were successfully treated by complete surgical resection without complication or
      recurrence. Considering the biological behavior of the intermediate type of
      neoplasm in IMT, we expect good survivals when achieving appropriate surgical
      resection without adjuvant therapy in infantile intra-abdominal IMT. 

PMID- 25061589
TI  - Omega-3 Polyunsaturated Fatty Acid for Cholestasis due to Bile Duct Paucity.
AB  - Omega (omega)-3 polyunsaturated fatty acids appear to be effective in preventing
      and treating parenteral nutrition-associated liver disease, and several
      mechanisms were proposed for this observation. An 8-week-old male infant with
      cholestasis and acholic stool was diagnosed non-syndromic intrahepatic
      interlobular bile duct paucity by open-wedge liver biopsy. Initially he was
      treated with usual supportive medical therapy, including ursodeoxycholic acid.
      However, the clinical status and laboratory tests did not improve. Omega (omega)
      3 polyunsaturated fatty acids (initially intravenous administration and oral
      administration later), were started and his liver function, including
      aminotransferase level and bilirubin levels normalized, and the ivory stool color
      turned green. We report the possible effectiveness of omega-3 polyunsaturated
      fatty acids as a potent choleretic agent for non-syndromic intrahepatic
      interlobular bile duct paucity, a very rare structural pediatric hepatic disease.

PMID- 25061590
TI  - Dedication: the korean society of pediatric gastroenterology, hepatology and
      nutrition celebrates the retirement of professor jeong kee seo.

PMID- 25061591
TI  - Anti-apoptotic effect of exercise on neuropsychiatric disorders.

PMID- 25061592
TI  - Psychopathology of social isolation.
AB  - The most important defining factor of being human is the use of symbolic
      language. Language or communication problem occurs during the growth, the child
      will have a higher risk of social isolation and then the survival will be
      threatened constantly. Today, adolescents and youths are familiar with computer
      and smart-phone devices, and communication with others by these devices is easy
      than face-to-face communication. As adolescents and youths live in the
      comfortable and familiar cyber-world rather than actively participating real
      society, so they make social isolation. Extreme form of this isolation in
      adolescents and youths is so-called Socially Withdrawn Youth. In this study, the
      psychopathological factors inducing social isolation were discussed. Development
      stages of social isolation in relation with types of social isolation, Ego
      syntonic isolation and Ego-dystonic isolation, were also considered. 

PMID- 25061593
TI  - Influence of mild traumatic brain injury during pediatric stage on short-term
      memory and hippocampal apoptosis in adult rats.
AB  - Traumatic brain injury (TBI) is a leading cause of neurological deficit in the
      brain, which induces short- and long-term brain damage, cognitive impairment
      with/without structural alteration, motor deficits, emotional problems, and death
      both in children and adults. In the present study, we evaluated whether mild TBI
      in childhood causes persisting memory impairment until adulthood. Moreover, we
      investigated the influence of mild TBI on memory impairment in relation with
      hippocampal apoptosis. For this, step-down avoidance task, terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and
      immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were
      used in the experiments. The animals were randomly divided into two groups: sham
      operation group and TBI-induction group. The mild TBI model was created with an
      electromagnetic contusion device activated at a velocity of 3.0 m/sec. The
      results showed that mild TBI during the pediatric stage significantly decreased
      memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were
      increased in the TBI-induction group compared to those in the sham-operation
      group. Defective memory retention and apoptosis sustained up to the adult stage.
      The present results shows that mild TBI induces long-lasting cognitive impairment
      from pediatric to adult stages in rats through the high level of apoptosis. The
      finding of this study suggests that children with mild TBI may need intensive
      treatments for the reduction of long-lasting cognitive impairment by secondary
      neuronal damage. 

PMID- 25061594
TI  - Treadmill exercise ameliorates disturbance of spatial learning ability in
      scopolamine-induced amnesia rats.
AB  - Alzheimer's disease is the most common neurodegenerative disease and this disease
      induces progressive loss of memory function Scopolamine is a non-selective
      muscarinic cholinergic receptor antagonist and it induces impairment of learning
      ability. Exercise is known to ameliorate memory deficits induced by various brain
      diseases. In the present study, we investigated the effect of treadmill exercise
      on spatial learning ability in relation with cell proliferation in the
      hippocampus using the scopolamine-induced amnesia mice. For the induction of
      amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once
      a day for 14 days. Morris water maze test for spatial learning ability was
      conducted. Immonofluorescence for 5-bromo-2-deoxyuri-dine (BrdU) and western blot
      for brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B
      (TrkB) were performed. In the present results, scopolamine-induced amnesia mice
      showed deterioration of spatial learning ability. Inhibition of cell
      proliferation and suppression of BDNF and TrkB expressions were observed in the
      scopolamine-induced amnesia mice. Treadmill exercise improved spatial learning
      ability and increased cell proliferation through activating of BDNF-TrkB pathway
      in the amnesia mice. These findings offer a possibility that treadmill exercise
      may provide preventive or therapeutic value for the memory loss induced by
      variable neurodegenerative diseases including Alzheimer's disease. 

PMID- 25061596
TI  - The effect of action observation training on knee joint function and gait ability
      in total knee replacement patients.
AB  - The purpose of this study is to investigate that effect of action observation
      training (AOT) on knee joint function and balance in total knee replacement (TKR)
      patients. The subjects consisted of eighteen post-TKR patients. All participants
      underwent conventional physical therapy. In addition, patients in the AOT group
      (n= 9) were asked to observe video clips showing daily actions and to imitate
      them afterward. Patients in the control group (n= 9) were asked to execute the
      same actions as patients in the AOT group. Outcome measures Western Ontario and
      Mc-Master Universities Osteoarthritis Index (WOMAC) included pain, stiffness,
      function and Timed Up and Go (TUG) test. After intervention, patients in the AOT
      group score better than patients in the control group. After TUG test, patients
      in the AOT group and control group were no significant difference between two
      groups. In addition to conventional physical therapy, AOT is effective in the
      rehabilitation of post-TKR patients. Action observation training is considered
      conducive to improving knee functions and ameliorating pain and stiffness, of
      patients who underwent TKR. 

PMID- 25061595
TI  - Treadmill exercise improves spatial learning ability by enhancing brain-derived
      neurotrophic factor expression in the attention-deficit/hyperactivity disorder
      rats.
AB  - Attention-deficit/hyperactivity disorder (ADHD) patients show learning difficulty
      and impulsiveness. Exercise is known to improve learning ability and memory
      function. In the present study, we investigated the duration-dependence of the
      effect of treadmill exercise on spatial learning ability in relation with brain
      derived neurotrophic factor (BDNF) expression in ADHD rats. For this study,
      radial 8-arm maze test and western blot for BDNF and tyrosine kinase B (TrkB)
      were performed. Spontaneous hypertensive rats were used as the ADHD rats and
      Wistar-Kyoto rats were used as the control rats. The rats in the exercise groups
      were forced to run on a treadmill for 10 min, 30 min, and 60 min once a day for
      28 consecutive days. ADHD rats displayed impairment of spatial learning ability,
      in contrast treadmill exercise ameliorated impairment of spatial learning
      ability. Treadmill exercise for 30 min per day showed most potent ameliorating
      effect on impairment of spatial learning ability. BDNF and TrkB expressions in
      the hippocampus were decreased in the ADHD rats, in contrast treadmill exercise
      enhanced BDNF and TrkB expressions. Treadmill exercise for 30 min and for 60 min
      per day showed enhancing effects on BDNF and TrkB expressions. Treadmill exercise
      alleviated deficits in the spatial learning ability through enhancing BDNF and
      TrkB expressions in the ADHD rats. Treadmill exercise for 30 min per day can be
      considered as the most effective therapeutic modality for the ADHD symptoms. 

PMID- 25061597
TI  - The effect of complex training on the children with all of the deformities
      including forward head, rounded shoulder posture, and lumbar lordosis.
AB  - The purpose of this study is to investigate the effect of complex training on
      children with the deformities including forward head, rounded shoulder posture,
      and lumbar lordosis. The complex training program was performed for 6 month three
      times per week. The complex training improved posture as measured by forward head
      angle (FHA), forward shoulder angle (FSA), and angle between anterior superior
      iliac spine and posterior superior iliac spine (APA). In the present results,
      complex training might overcome vertebral deformity through decreasing forward
      head, rounded shoulder posture, and lumbar lordosis and increasing flexibility in
      the children. 

PMID- 25061598
TI  - The effect of the action observation physical training on the upper extremity
      function in children with cerebral palsy.
AB  - The purpose this study was to investigate the effect of action observation
      physical training (AOPT) on the functioning of the upper extremities in children
      with cerebral palsy (CP), using an evaluation framework based on that of the
      International Classification of Functioning, Disability and Health (ICF). The
      subjects were divided into an AOPT group and a physical training (PT) group. AOPT
      group practiced repeatedly the actions they observed on video clips, in which
      normal child performed an action with their upper extremities. PT group performed
      the same actions as the AOPT group did after observing landscape photographs. The
      subjects participated in twelve 30-min sessions, 3 days a week, for 4 weeks.
      Evaluation of upper extremity function using the following: the power of grasp
      and Modified Ashworth Scale for body functions and structures, a Box and Block
      test, an ABILHAND-Kids questionnaire, and the WeeFIM scale for activity and
      participation. Measurements were performed before and after the training, and 2
      weeks after the end of training. The results of this study showed that, in
      comparison with the PT group, the functioning of the upper extremities in the
      AOPT group was significantly improved in body functions and activity and
      participation according to the ICF framework. This study demonstrates that AOPT
      has a positive influence on the functioning of the upper extremities in children
      with CP. It is suggested that this alternative approach for functioning of the
      upper extremities could be an effective method for rehabilitation in children
      with CP. 

PMID- 25061599
TI  - The effects of aquatic exercise on body composition, physical fitness, and
      vascular compliance of obese elementary students.
AB  - The purpose of this study was to investigate the effects of aquatic exercise on
      body composition, physical fitness, and vascular compliance of obese elementary
      school students. For the purpose of this study, 20 obese elementary students were
      selected as subjects. The subjects were then divided into two groups: the
      swimming group (n= 10) and the control group (n= 10). The subjects were asked to
      exercise for 60 minutes a day, 3 times a week for 12 weeks with an exercise
      intensity of 50-70% HRmax. The following results were achieved: first, in terms
      of body composition, both body fat percentage and fat-free mass showed
      significant differences within the swimming group. There were also significant
      differences again in the posttest of difference between the two groups. Second,
      in terms of changes in physical fitness, there were, again, no significant
      changes in muscular strength between the two groups. However, muscular endurance,
      flexibility, and cardiopulmonary endurance showed significant differences in the
      swimming group's test for difference within groups. Significant differences in
      both groups for the posttest of differences between groups were also seen. Third,
      in terms of vascular compliance, there was a significant increase in the right
      leg for the swimming groups' test of difference within groups, as well as in the
      posttest of difference between groups. 

PMID- 25061600
TI  - Feasibility of integrating the "Healthy moves for aging well" program into home
      care aide services for frail older adults.
AB  - The purpose of the study was to assess the feasibility of implementing simple,
      safe, non-equipment evidence-based movements (Healthy Moves for Aging Well
      program) using an affordable and sustainable homecare-aide based delivery model
      that reaches the maximum possible number of frail older adults living at home in
      Illinois. Two local agencies were asked to identify two experienced home care
      aides and two inexperienced home care aides (n= 8). Each home care aides
      delivered the Healthy Moves to four clients (n= 16). Eight home care aides
      visited the client in the home and were asked to deliver the Healthy Moves
      program on a regular basis for a four-month time period. Outcome measures
      included a pre-and post- survey, a functional fitness test (older adults), and
      interviews. Evaluation procedures focused on older adult participants, homecare
      aids, and sites. The results showed that both interview and survey data revealed
      that most participants including older adults, home care aides, and site
      directors had a positive perception and high satisfaction with the program.
      Specially, 100% of older adult participants reported that they would recommend
      the program to others. Additionally, seniors and home care aides reported that
      they enjoyed working with each other on the program and both site directors
      reported that dissemination of the program in the State of Illinois employing
      home care aides was feasible and acceptable. Our study results indicate that
      Healthy Moves for Aging Well could be safely and successfully be disseminated to
      frail older adults in the State of Illinois. 

PMID- 25061602
TI  - Involvement of the inconstant bursa of the fifth metatarsophalangeal joint in
      psoriatic arthritis: a clinical and ultrasonographic study.
AB  - OBJECTIVE: To evaluate the involvement of the bursa located next to the head of
      the 5th metatarsal bone in patients with psoriatic arthritis (PsA) in comparison
      with the other seronegative spondyloarthritis (SpA). METHODS: All patients with
      PsA seen during a period of 24 months were enrolled. The control group included
      healthy subjects and patients with the other SpA. All subjects underwent clinical
      and ultrasound (US) examination of the lateral surface of the 5th metatarsal.
      RESULTS: 150 PsA patients (88 M; 62 F), 172 SpA (107 M; 65 F), and 95 healthy
      controls (58 M; 37 F) were evaluated. Based on clinical and US evaluation,
      bursitis was diagnosed in 17/150 (11.3%) PsA patients but in none of the SpA (P <
      0.0001) and healthy (P = 0.0002) controls. In detecting bursitis, US was more
      sensitive than clinical examination, although the difference did not reach
      statistical significance (P = 0.09). CONCLUSION: The bursa of the 5th
      metatarsophalangeal joint appears to be involved in PsA more frequently than by
      chance. If confirmed by other studies, this finding could be considered as a
      distinctive clinical sign of PsA, useful for differential diagnosis with the
      other SpA. In asymptomatic patients, US proved to be more sensitive in the
      detection of bursitis.

PMID- 25061601
TI  - Circulating endothelial-derived activated microparticle: a useful biomarker for
      predicting one-year mortality in patients with advanced non-small cell lung
      cancer.
AB  - BACKGROUND: This study tested the hypothesis that circulating microparticles
      (MPs) are useful biomarkers for predicting one-year mortality in patients with
      end-stage non-small cell lung cancer (ES-NSCLC). METHODS AND RESULTS: One hundred
      seven patients were prospectively enrolled into the study between April 2011 and
      February 2012, and each patient received regular follow-up after enrollment.
      Levels of four MPs in circulation, (1) platelet-derived activated MPs (PDAc-MPs),
      (2) platelet-derived apoptotic MPs (PDAp-MPs), (3) endothelial-derived activated
      MPs (EDAc-MPs), and (4) endothelial-derived apoptotic MPs (EDAp-MPs), were
      measured just after the patient was enrolled into the study using flow cytometry.
      Patients who survived for more than one year were categorized into group 1 (n =
      56) (one-year survivors) and patients who survived less than one year were
      categorized into group 2 (n = 51) (one-year nonsurvivors). Male gender, incidence
      of liver metastasis, progression of disease after first-line treatment, poor
      performance status, and the Charlson comorbidity index were significantly higher
      in group 2 than in group 1 (all P < 0.05). Additionally, as measured by flow
      cytometry, only the circulating level of EDAc-MPs was found to be significantly
      higher in group 2 than in group 1 (P = 0.006). Multivariate analysis demonstrated
      that circulating level of EDAc-MPs along with brain metastasis and male gender
      significantly and independently predictive of one-year mortality (all P < 0.035).
      CONCLUSION: Circulating EDAc-MPs may be a useful biomarker predictive of one-year
      morality in ES-NSCLC patients.

PMID- 25061604
TI  - Repairing the osteochondral defect in goat with the tissue-engineered
      osteochondral graft preconstructed in a double-chamber stirring bioreactor.
AB  - To investigate the reparative efficacy of tissue-engineered osteochondral (TEO)
      graft for repairing the osteochondral defect in goat, we designed a double
      chamber stirring bioreactor to construct the bone and cartilage composites
      simultaneously in one beta-TCP scaffold and observed the reparative effect in
      vivo. The osteochondral defects were created in goats and all the animals were
      divided into 3 groups randomly. In groups A, the defect was treated with the TEO
      which was cultured with mechanical stimulation of stir; in group B, the defect
      was treated with TEO which was cultured without mechanical stimulation of stir;
      in groups C, the defect was treated without TEO. At 12 weeks and 24 weeks after
      operation, the reparative effects in different groups were assessed and compared.
      The results indicated that the reparative effect of the TEO cultured in the
      bioreactor was better than the control group, and mechanical stimulation of stir
      could further improve the reparative effect. We provided a feasible and effective
      method to construct the TEO for treatment of osteochondral defect using
      autologous BMSCs and the double-chamber bioreactor. 

PMID- 25061603
TI  - Amelioration of colitis in mouse model by exploring antioxidative potentials of
      an indigenous probiotic strain of Lactobacillus fermentum Lf1.
AB  - Based on the preliminary screening of eight indigenous putative probiotic
      Lactobacilli, Lactobacillus fermentum Lf1 was selected for assessing its
      antioxidative efficacy in DSS colitis mouse model based on its ability to enhance
      the expression of "Nrf2" by 6.43-fold and malondialdehyde (MDA) inhibition by
      78.1 +/- 0.24% in HT-29 cells under H2O2 stress. The Disease Activity Index and
      histological scores of Lf1-treated mice were lower than the control group.
      However, expression of "Nrf2" was not observed in Lf1-treated mice. A significant
      increase in the expression of antioxidative enzymes such as SOD2 and TrxR-1 was
      recorded in both of the groups. The expression of SOD2 was significantly
      downregulated in colitis-induced mice by -100.00-fold relative to control group,
      and the downregulation was considerably reduced to -37.04-fold in colitis Lf1
      treatment group. Almost, a similar trend was recorded in case of "thioredoxin"
      expression, though "CAT" was refractile to expression. The Lf1-treated group had
      decreased malondialdehyde level as compared to colitis control (37.92 +/- 6.31
      versus 91.13 +/- 5.76 MUM/g). These results point towards Lf1-induced activation
      of the antioxidant enzyme system in the mouse model and its prospects to be
      explored as a new strategy for IBD management.

PMID- 25061605
TI  - Advance in ERG analysis: from peak time and amplitude to frequency, power, and
      energy.
AB  - PURPOSE: To compare time domain (TD: peak time and amplitude) analysis of the
      human photopic electroretinogram (ERG) with measures obtained in the frequency
      domain (Fourier analysis: FA) and in the time-frequency domain (continuous (CWT)
      and discrete (DWT) wavelet transforms). METHODS: Normal ERGs (n = 40) were
      analyzed using traditional peak time and amplitude measurements of the a- and b
      waves in the TD and descriptors extracted from FA, CWT, and DWT. Selected
      descriptors were also compared in their ability to monitor the long-term
      consequences of disease process. RESULTS: Each method extracted relevant
      information but had distinct limitations (i.e., temporal and frequency
      resolutions). The DWT offered the best compromise by allowing us to extract more
      relevant descriptors of the ERG signal at the cost of lesser temporal and
      frequency resolutions. Follow-ups of disease progression were more prolonged with
      the DWT (max 29 years compared to 13 with TD). CONCLUSIONS: Standardized time
      domain analysis of retinal function should be complemented with advanced DWT
      descriptors of the ERG. This method should allow more sensitive/specific
      quantifications of ERG responses, facilitate follow-up of disease progression,
      and identify diagnostically significant changes of ERG waveforms that are not
      resolved when the analysis is only limited to time domain measurements.

PMID- 25061606
TI  - Correlates of smoke-free home policies in Shanghai, China.
AB  - BACKGROUND: Approximately 63.7% of nonsmokers in China are exposed to secondhand
      smoke (SHS) in their homes. The current study documents the prevalence and
      correlates of smoke-free home policies in Shanghai, as well as reasons for
      implementing such a policy and places where smoking is most commonly allowed.
      METHODS: We conducted in-person surveys of 500 participants using a multistage
      proportional random sampling design in an urban and suburban district. RESULTS:
      Overall, 35.3% had a smoke-free home policy. In the logistic regression, having
      higher income, not having smokers in the home, having children in the home,
      having fewer friends/relatives who permit smoking at home, and not being a
      current smoker were correlates of having a smoke-free home policy (P < 0.05).
      Concern about the health impact of SHS was reportedly the most important reason
      for establishing a smoke-free home. Among participants with no or partial bans,
      the most common places where smoking was allowed included the living room
      (64.2%), kitchen (46.1%), and bathroom (33.8%). CONCLUSIONS: Smoke-free home
      policies were in place for a minority of households surveyed. Establishing such a
      policy was influenced by personal smoking behavior and social factors. These
      findings suggest an urgent need to promote smoke-free home policies through
      tobacco control programs.

PMID- 25061607
TI  - Development of the Sri Lankan early teenagers' violence inventory: an instrument
      to measure peer violence in schools.
AB  - This study was designed to develop an inventory to measure peer violence among
      early teens (13-15 years of age) in schools in Sri Lanka. Development of SLETVI
      was carried out in two phases. In phase I, development of an operational
      definition for peer violence, identification, and finalizing violent acts for
      inventory was done by a combination of qualitative methods: a comprehensive
      literature review, focus group discussions among 13-15-year-old adolescents,
      their teachers and parents, and consultative meetings with experts in the field.
      Inventory was then pretested. In phase II, elaboration of SLETVI was carried out
      by administering it to a sample of 1700 adolescents (13-15 years old).
      Exploratory factor analysis using principal component analysis was performed
      separately for experiences of victimization and perpetration. Test-retest
      reliability of SLETVI was assessed. SLETVI included 37 items in three factors:
      "less severe violence," "severe physical," and "severe relational" violence.
      Combined use of qualitative and quantitative methods enabled development of a
      culturally valid and reliable operational inventory to assess early teenagers'
      peer violence in Sri Lankan and other South Asian schools. 

PMID- 25061608
TI  - Cofactor independent phosphoglycerate mutase of Brugia malayi induces a mixed
      Th1/Th2 type immune response and inhibits larval development in the host.
AB  - Lymphatic filariasis is a major debilitating disease, endemic in 72 countries
      putting more than 1.39 billion people at risk and 120 million are already
      infected. Despite the significant progress in chemotherapeutic advancements,
      there is still need for other measures like development of an effective vaccine
      or discovery of novel drug targets. In this study, structural and immunological
      characterization of independent phosphoglycerate mutase of filarial parasite
      Brugia malayi was carried out. Protein was found to be expressed in all major
      parasite life stages and as an excretory secretory product of adult parasites. Bm
      iPGM also reacted to all the categories of human bancroftian patient's sera
      including endemic normals. In vivo immunological behaviour of protein was
      determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c
      mice and Mastomys coucha. Immunization with Bm-iPGM led to generation of a mixed
      Th1/Th2 type immune response offering 58.2% protection against larval challenge
      in BALB/c and 65-68% protection in M. coucha. In vitro studies confirmed
      participation of anti-Bm-iPGM antibodies in killing of B. malayi infective larvae
      and microfilariae through ADCC mechanism. The present findings reveal potential
      immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial
      vaccine candidate. 

PMID- 25061610
TI  - Multisensory integration and internal models for sensing gravity effects in
      primates.
AB  - Gravity is crucial for spatial perception, postural equilibrium, and movement
      generation. The vestibular apparatus is the main sensory system involved in
      monitoring gravity. Hair cells in the vestibular maculae respond to
      gravitoinertial forces, but they cannot distinguish between linear accelerations
      and changes of head orientation relative to gravity. The brain deals with this
      sensory ambiguity (which can cause some lethal airplane accidents) by combining
      several cues with the otolith signals: angular velocity signals provided by the
      semicircular canals, proprioceptive signals from muscles and tendons, visceral
      signals related to gravity, and visual signals. In particular, vision provides
      both static and dynamic signals about body orientation relative to the vertical,
      but it poorly discriminates arbitrary accelerations of moving objects. However,
      we are able to visually detect the specific acceleration of gravity since early
      infancy. This ability depends on the fact that gravity effects are stored in
      brain regions which integrate visual, vestibular, and neck proprioceptive signals
      and combine this information with an internal model of gravity effects. 

PMID- 25061611
TI  - A comparison between gadofosveset trisodium and gadobenate dimeglumine for steady
      state MRA of the thoracic vasculature.
AB  - PURPOSE: Retrospective comparison between gadofosveset trisodium and gadobenate
      dimeglumine steady state magnetic resonance angiography (SS-MRA) of the thoracic
      vasculature at 1.5T using signal-to-noise ratio (SNR) and vessel edge sharpness
      (ES) as markers of image quality. MATERIALS AND METHODS: IRB approval was
      obtained. Twenty separate patients each underwent SS-MRA using high-resolution 3D
      ECG-triggered coronal IR-TFE at 1.5T approximately 3-4 minutes following 10 or 15
      mL gadofosveset or 20 mL gadobenate. ROIs were placed in the right atrium, left
      ventricle, left atrium, ascending aorta, descending aorta, and right pulmonary
      artery to estimate SNR. Vessel ES was estimated as 20-80% rise distances from
      line intensity profiles in the left pulmonary vein, ascending aorta, and
      descending aorta. Data were analyzed using nonpaired Student's t-test (threshold
      for significance set at P < 0.05). RESULTS: There was no significant difference
      in mean SNR for the gadofosveset or gadobenate groups (P values: 0.14 to 0.85).
      There was no significant difference in mean vessel ES for gadofosveset and
      gadobenate groups (P values: 0.17 to 0.78). CONCLUSION: High quality thoracic SS
      MRA can be achieved with gadobenate dimeglumine, similar to that achieved with
      the blood pool agent gadofosveset trisodium provided that imaging is initiated
      quickly (3-4 min) after contrast injection.

PMID- 25061609
TI  - Role of endoplasmic reticulum stress in atherosclerosis and diabetic
      macrovascular complications.
AB  - Age-related changes in endoplasmic reticulum (ER) are associated with stress of
      this cell organelle. Unfolded protein response (UPR) is a normal physiological
      reaction of a cell in order to prevent accumulation of unfolded and misfolded
      proteins in the ER and improve the normal ER function. However, in pathologic
      conditions such as atherosclerosis, obesity, and diabetes, ER function becomes
      impaired, leading to the development of ER stress. In chronic ER stress,
      defective posttranslational protein folding results in deposits of aberrantly
      folded proteins in the ER and the induction of cell apoptosis mediated by UPR
      sensors C/EBPalpha-homologous protein (CHOP) and inositol requiring protein-1
      (IRE1). Since ER stress and ER-induced cell death play a nonredundant role in the
      pathogenesis of atherosclerosis and diabetic macrovascular complications,
      pharmaceutical targeting of ER stress components and pathways may be beneficial
      in the treatment and prevention of cardiovascular pathology. 

PMID- 25061612
TI  - Anthropometric characteristics and sex influence magnitude of skin cooling
      following exposure to whole body cryotherapy.
AB  - This study explored whether anthropometric measures influence magnitude of skin
      cooling following exposure to whole body cryotherapy (WBC). Height, weight, body
      fat percentage, and lean mass were measured in 18 male and 14 female
      participants. Body surface area, body surface area to mass ratio, body mass
      index, fat-free mass index, and fat mass index were calculated. Thermal images
      were captured before and after WBC (-60 degrees C for 30 seconds, -110 degrees C
      for 2 minutes). Skin temperature was measured at the chest, arm, thigh, and calf.
      Mean skin temperature before and after WBC and change in mean skin temperature
      (DeltaT sk) were calculated. DeltaT sk was significantly greater in females
      (12.07 +/- 1.55 degrees C) than males (10.12 +/- 1.86 degrees C; t(30) = -3.09, P
      = .004). A significant relationship was observed between body fat percentage and
      DeltaT sk in the combined dataset (P = .002, r = .516) and between fat-free mass
      index and DeltaT sk in males (P = .005, r = .622). No other significant
      associations were found. Skin response of individuals to WBC appears to depend
      upon anthropometric variables and sex, with individuals with a higher adiposity
      cooling more than thinner individuals. Effects of sex and anthompometrics should
      be considered when designing WBC research or treatment protocols. 

PMID- 25061614
TI  - Day-ahead crude oil price forecasting using a novel morphological component
      analysis based model.
AB  - As a typical nonlinear and dynamic system, the crude oil price movement is
      difficult to predict and its accurate forecasting remains the subject of intense
      research activity. Recent empirical evidence suggests that the multiscale data
      characteristics in the price movement are another important stylized fact. The
      incorporation of mixture of data characteristics in the time scale domain during
      the modelling process can lead to significant performance improvement. This paper
      proposes a novel morphological component analysis based hybrid methodology for
      modeling the multiscale heterogeneous characteristics of the price movement in
      the crude oil markets. Empirical studies in two representative benchmark crude
      oil markets reveal the existence of multiscale heterogeneous microdata structure.
      The significant performance improvement of the proposed algorithm incorporating
      the heterogeneous data characteristics, against benchmark random walk, ARMA, and
      SVR models, is also attributed to the innovative methodology proposed to
      incorporate this important stylized fact during the modelling process. Meanwhile,
      work in this paper offers additional insights into the heterogeneous market
      microstructure with economic viable interpretations. 

PMID- 25061615
TI  - Estrogen Receptor Alpha Binding to ERE is Required for Full Tlr7- and Tlr9
      Induced Inflammation.
AB  - We previously found that a maximum innate inflammatory response induced by
      stimulation of Toll-like receptors (TLRs) 3, 7 and 9 requires ERalpha, but does
      not require estrogen in multiple cell types from both control and lupus-prone
      mice. Given the estrogen-independence, we hypothesized that ERalpha mediates TLR
      signaling by tethering to, and enhancing, the activity of downstream
      transcription factors such as NFkappaB, rather than acting classically by binding
      EREs on target genes. To investigate the mechanism of ERalpha impact on TLR
      signaling, we utilized mice with a knock-in ERalpha mutant that is unable to bind
      ERE. After stimulation with TLR ligands, both ex vivo spleen cells and bone
      marrow-derived dendritic cells (BM-DCs) isolated from mutant ERalpha ("KIKO")
      mice produced significantly less IL-6 compared with cells from wild-type (WT)
      littermates. These results suggest that ERalpha modulation of TLR signaling does
      indeed require ERE binding for its effect on the innate immune response.

PMID- 25061616
TI  - The times they are a-changin'.

PMID- 25061613
TI  - Immunopathogenesis of ocular Behcet's disease.
AB  - Behcet's disease (BD) is a chronic recurrent systemic inflammatory disorder of
      unknown etiology characterized by oral and genital ulcerations, skin lesions, and
      uveitis. The ocular involvement of BD, or Behcet's uveitis (BU), is characterized
      by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to
      be more recurrent and sight threatening than other endogenous autoimmune
      uveitides, despite aggressive immunosuppression. Although pathogenesis of BD is
      unclear, researches have revealed that immunological aberrations may be the
      cornerstone of BD development. General hypothesis of BD pathogenesis is that
      inflammatory response is initiated by infectious agents or autoantigens in
      patients with predisposing genetic factors and perpetuated by both innate and
      acquired immunity. In addition, a network of immune mediators plays a substantial
      role in the inflammatory cascade. Recently, we found that the immunopathogenesis
      of BU is distinct from other autoimmune uveitides regarding intraocular effector
      cell profiles, maturation markers of dendritic cells, and the cytokine/chemokine
      environment. In addition, accumulating evidence indicates the involvement of Th17
      cells in BD and BU. Recent studies on genetics and biologics therapies in
      refractory BU also support the immunological association with the pathogenesis of
      BU. In this review, we provide an overview of novel findings regarding the
      immunopathogenesis of BU. 

PMID- 25061617
TI  - How optimistic should we be about family medicine?

PMID- 25061618
TI  - Health care reform: possibilities & opportunities for primary care.
AB  - Amid the swirl of change in today's US health care system, there are
      opportunities for new care delivery models to slow rising costs and improve
      outcomes in family medicine. This review summarizes the possibilities. 

PMID- 25061619
TI  - Fatigue, arthralgia, amenorrhea--Dx?
AB  - A 46-year-old Caucasian female with a history of epilepsy came into our family
      medicine center complaining of weakness, fatigue, and arthralgia that made it
      difficult for her to walk. She'd had these symptoms for 6 months and reported
      having amenorrhea and hot flashes for the past 2 years. 

PMID- 25061620
TI  - Autism: 5 misconceptions that can complicate care.

PMID- 25061621
TI  - Autism: why the rise in rates?

PMID- 25061622
TI  - Teenager with shortness of breath and hypoxia.

PMID- 25061623
TI  - Clinical inquiry: do complementary agents lower HbA1c when used with standard
      type 2 diabetes therapy?

PMID- 25061624
TI  - PURLs: Think twice about nebulizers for asthma attacks.

PMID- 25061625
TI  - Clinical inquiry: what is the best treatment for impetigo ?

PMID- 25061626
TI  - PURLs: Why you shouldn't start beta-blockers before surgery.

PMID- 25061627
TI  - Intrauterine fetal demise: care in the aftermath, and beyond.

PMID- 25061628
TI  - A better approach to opioid prescribing in primary care.
AB  - PURPOSE: Primary care physicians are at the center of a national prescription
      opioid epidemic, with little training or knowledge about the management of
      patients on opioids for chronic noncancer pain (CNCP). We developed an electronic
      medical record (EMR)-based protocol and educational intervention to standardize
      documentation and management of patients prescribed opioids by primary care
      providers. Our objective was to evaluate provider adherence to this protocol,
      attitudes toward the management of these patients, and knowledge of opioid
      prescribing. METHODS: We trained providers and select staff from 3 primary care
      practices at the Division of General Internal Medicine at the University of
      Pennsylvania in the use of a protocol for managing patients taking opioids for
      CNCP. The following served as measures of protocol adherence: 1) the provider
      used a standard diagnosis (chronic pain, ICD-9 code 338.29A) in the problem list,
      2) the provider ordered at least one urine drug screen (UDS) for the patient in
      the past year, and 3) the patient came in for at least one office visit every 6
      months. We assessed physician and staff attitudes and knowledge with pre- and
      post-intervention surveys. Adherence to the protocol was linked to a monetary
      incentive. RESULTS: Provider adherence to the protocol significantly improved
      measured outcomes. The number of UDSs ordered increased by 145%, and the
      diagnosis of chronic pain on the problem list increased by 424%. There was a
      statistically significant improvement in providers' role adequacy, role support,
      and job satisfaction/role-related self-esteem when working with patients taking
      opioids. In addition, provider knowledge of proper management of these patients
      improved significantly. Eighty-nine percent of our physicians attained the
      monetary incentive. CONCLUSIONS: We developed a quality improvement intervention
      that addressed the need for better regulation of opioid prescribing, resulted in
      increased adherence to best-practice guidelines, and improved provider knowledge
      and attitudes.

PMID- 25061629
TI  - Biofeedback: a way to regain some control over pain.
AB  - Integrating biofeedback into a patient's treatment plan can ease pain and improve
      quality of life. 

PMID- 25061630
TI  - Sleep dysfunction, diabetes, and pain: a troublesome triad.
AB  - Critical to helping patients break the stranglehold of these 3 comorbidities is
      an understanding of how they interact with one other. 

PMID- 25061631
TI  - Assessing suicide risk in patients with chronic pain and depression.
AB  - Nearly one-half of all patients seen in primary care experience persistent pain,
      and major depressive disorder is a common comorbidity with chronic pain. 

PMID- 25061632
TI  - Analysis and discrimination of grape spoilage via volatiles: a comparison between
      long optical path Fourier-transform-infrared spectroscopy and sensor arrays.
AB  - Fruits release specific volatiles as vapors during spoilage that can provide
      information about the spoilage stages of fruits. We used long optical path
      Fourier Transform Infrared Spectroscopy (FTIR) and sensor arrays comprising
      carbon dioxide and ethanol sensors to study the grape spoilage process
      synchronously. The results revealed that specific volatiles, such as carbon
      dioxide, ethanol and esters, are released from grapes during spoilage. The
      presence and concentrations of these compounds gradually change with storage
      time. Through chemometric analysis, the infrared spectra of volatiles from
      different spoilage stages of grapes were successfully classified. As a simple
      form of instrumentation, the sensor arrays also have the ability to discriminate
      whether the grapes have decayed. We established a Soft Independent Modeling of
      Class Analogy (SIMCA) model to classify the grape samples into different spoilage
      stages, and the model according to different quantities of grapes is also
      discussed. This study demonstrates that it is possible to characterize grape
      spoilage by analyzing the released volatiles. 

PMID- 25061633
TI  - A 1D dysprosium chain with slow magnetic relaxation constructed from a pyridine-N
      oxide ligand.
AB  - A novel 1D dysprosium complex was synthesized by employing a pyridine-N-oxide
      ligand. It exhibits slow magnetic relaxation with an energy barrier of 227 K
      under zero dc field. 

PMID- 25061634
TI  - Electrodeposition of gallium in the presence of NH4Cl in an ionic liquid: hints
      for GaN formation.
AB  - Group III-V semiconductors are important in the production of a variety of
      optoelectronic devices. At present, these semiconductors are synthesized by high
      vacuum techniques. Here we report on the electrochemical deposition of GaN which
      seems to form in quite a thin layer from NH4Cl and GaCl3 in an ionic liquid. 

PMID- 25061635
TI  - Incorporation of iron hydrogenase active sites into a highly stable metal-organic
      framework for photocatalytic hydrogen generation.
AB  - A new biomimetic heterogeneous photocatalyst ([FeFe]@ZrPF) has been synthesized
      through the incorporation of homogeneous complex 1 [(i-SCH2)2NC(O)C5H4N]
      [Fe2(CO)6] into the highly robust zirconium-porphyrin based metal-organic
      framework (ZrPF). The immobilized biomimetic [Fe2S2] catalyst inside the MOF
      shows great improvement in hydrogen generation compared to the reference
      homogeneous catalyst complex 1.

PMID- 25061636
TI  - Unique ultrafast energy transfer in a series of phenylene-bridged subporphyrin
      porphyrin hybrids.
AB  - A series of phenylene-bridged subporphyrin-Zn(II) porphyrin (SubP-ZnP) hybrid
      systems undergo extraordinarily fast excitation energy transfer (EET) processes
      from the SubP to the ZnP, aided by conjugative electronic elongation of the SubP
      to the phenylene-bridge.

PMID- 25061637
TI  - Silicon diatom frustules as nanostructured photoelectrodes.
AB  - In the quest for solutions to meeting future energy demands, solar fuels play an
      important role. A particularly promising example is photocatalysis since even
      incremental improvements in performance in this process are bound to translate
      into significant cost benefits. Here, we report that semiconducting and high
      surface area 3D silicon replicas prepared from abundantly available diatom
      fossils sustain photocurrents and enable solar energy conversion. 

PMID- 25061638
TI  - Highly efficient anti-cancer therapy using scorpion 'NanoVenin'.
AB  - Host defence peptidotoxins from animal venoms have been identified to possess
      substantial anticancer properties. Towards a safer, translatable approach, we
      have developed a viable chemical methodology based on a well-defined, self
      assembled polymeric nano-architecture for controlled delivery of toxins derived
      from scorpion venom. 

PMID- 25061639
TI  - Obituary: Maureen Young, 1915-2013.

PMID- 25061640
TI  - Reply to Liu: Amino acid 104 asparagine/glutamic acid of p53 is an adaptively
      selected site for extreme environments in mammals of the Tibet plateau.

PMID- 25061641
TI  - Reply to Skalsky et al.: A microRNA-like small RNA from Dengue virus.

PMID- 25061642
TI  - [Rheumatism: immunosuppressants and operation].

PMID- 25061643
TI  - Europe: FCTC article 5.3 complaint.

PMID- 25061644
TI  - Poland: 'truth' style counter tobacco industry campaign.

PMID- 25061645
TI  - World: poor sales blamed for factory closures.

PMID- 25061646
TI  - Germany: international vaporfair.

PMID- 25061647
TI  - Malaysia: empowering dentists into smoking cessation.

PMID- 25061648
TI  - [Rheumatology].

PMID- 25061649
TI  - Diversity: equal access.

PMID- 25061650
TI  - Protocol-based care for early septic shock.

PMID- 25061651
TI  - [Comparison of recurrence patterns in esophageal carcinoma after surgery alone
      and surgery after neoadjuvant chemoradiotherapy: a secondary analysis of the
      CROSS study].

PMID- 25061652
TI  - [Significant cardiotoxicity of trastuzumab in adjuvant systemic therapy of
      elderly patients with breast cancer].

PMID- 25061653
TI  - Resident rounds part III: plaque on left areola of an African-American woman.
AB  - Basal cell carcinoma (BCC) is the most common cutaneous malignancy, and usually
      presents on sun-exposed areas of the skin. Unsurprisingly, BCC appearing on the
      nipple-areola complex (NAC) is rare, and even more so in females and dark skin
      types. BCC of the NAC is more aggressive than other locations, thus diagnosis and
      treatment are imperative. We present a case of an African American female with a
      lichenified, scaly plaque on her left areola that was unresponsive to clobetasol.
      After biopsy, the lesion was identified as pigmented BCC of the NAC. The patient
      denied surgical treatment and was treated with topical 5-fluorouracil. The BCC
      initially resolved but recurred at 22 month follow-up. We plan to treat the
      recurrence with Mohs surgery.

PMID- 25061654
TI  - [Waiting ("Watch and Wait") for complete clinical remission after neoadjuvant
      radiochemotherapy of rectal carcinomas: influence of salvage-therapy on local
      tumor control].

PMID- 25061655
TI  - Bone transport of the tibia with a motorized intramedullary lengthening nail--a
      case report.

PMID- 25061656
TI  - Cemented or uncemented hemiarthroplasty for the treatment of femoral neck
      fractures?

PMID- 25061657
TI  - Distributing a limited resource: ethical allocation of deceased donor kidneys.

PMID- 25061658
TI  - Range of services remains popular.

PMID- 25061659
TI  - Steady stream of variety.

PMID- 25061660
TI  - In situ formation of carbon nanotubes encapsulated within boron nitride nanotubes
      via electron irradiation.
AB  - We report experimental evidence of the formation by in situ electron-irradiation
      of single-walled carbon nanotubes (C-NT) confined within boron nitride nanotubes
      (BN-NT). The electron radiation stemming from the microscope supplies the energy
      required by the amorphous carbonaceous structures to crystallize in a tubular
      form in a catalyst-free procedure, at room temperature and high vacuum. The
      structural defects resulting from the interaction of the shapeless carbon with
      the BN nanotube are corrected in a self-healing process throughout the
      crystallinization. Structural changes developed during the irradiation process
      such as defects formation and evolution, shrinkage, and shortness of the BN-NT
      were in situ monitored. The outer BN wall provides a protective and insulating
      shell against environmental perturbations to the inner C-NT without affecting
      their electronic properties, as demonstrated by first-principles calculations.

PMID- 25061661
TI  - Increased hyaluronan levels in HABP1/p32/gC1qR overexpressing HepG2 cells inhibit
      autophagic vacuolation regulating tumor potency.
AB  - Tumor growth and development is influenced by its microenvironment. A major
      extracellular matrix molecule involved in cancer progression is hyaluronan (HA).
      Hyaluronan and expression of a number of hyaladherin family proteins are
      dramatically increased in many cancer malignancies. One such hyaladherin,
      hyaluronan-binding protein 1 (HABP1/p32/gC1qR) has been considered to be a
      biomarker for tumor progression. Interestingly, overexpression of HABP1 in
      fibroblast has been shown to increase autophagy via generation of excess reactive
      oxygen species (ROS) and depletion of HA leading to apoptosis. Cancerous cells
      are often found to exhibit decreased rate of proteolysis/autophagy in comparison
      to their normal counterparts. To determine if HABP1 levels alter tumorigenicity
      of cancerous cells, HepR21, the stable transfectant overexpressing HABP1 in HepG2
      cell line was derived. HepR21 has been shown to have increased proliferation rate
      than HepG2, intracellular HA cable formation and enhanced tumor potency without
      any significant alteration of intracellular ROS. In this paper we have observed
      that HepR21 cells containing higher endogenous HA levels, have downregulated
      expression of the autophagic marker, MAP-LC3, consistent with unaltered levels of
      endogenous ROS. In fact, HepR21 cells seem to have significant resistance to
      exogenous ROS stimuli and glutathione depletion. HepR21 cells were also found to
      be more resilient to nutrient starvation in comparison to its parent cell line.
      Decline in intracellular HA levels and HA cables in HepR21 cells upon treatment
      with HAS inhibitor (4-MU), induced a surge in ROS levels leading to increased
      expression of MAP-LC3 and tumor suppressors Beclin 1 and PTEN. This suggests the
      importance of HABP1 induced HA cable formation in enhancing tumor potency by
      maintaining the oxidant levels and subsequent autophagic vacuolation. 

PMID- 25061662
TI  - Attachment and children's biased attentional processing: evidence for the
      exclusion of attachment-related information.
AB  - Research in both infants and adults demonstrated that attachment expectations are
      associated with the attentional processing of attachment-related information.
      However, this research suffered from methodological issues and has not been
      validated across ages. Employing a more ecologically valid paradigm to measure
      attentional processes by virtue of eye tracking, the current study tested the
      defensive exclusion hypothesis in late childhood. According to this hypothesis,
      insecurely attached children are assumed to defensively exclude attachment
      related information. We hypothesized that securely attached children process
      attachment- related neutral and emotional information in a more open manner
      compared to insecurely attached children. Sixty-two children (59.7% girls, 8-12
      years) completed two different tasks, while eye movements were recorded: task one
      presented an array of neutral faces including mother and unfamiliar women and
      task two presented the same with happy and angry faces. Results indicated that
      more securely attached children looked longer at mother's face regardless of the
      emotional expression. Also, they tend to have more maintained attention to
      mother's neutral face. Furthermore, more attachment avoidance was related to a
      reduced total viewing time of mother's neutral, happy, and angry face. Attachment
      anxiety was not consistently related to the processing of mother's face. Findings
      support the theoretical assumption that securely attached children have an open
      manner of processing all attachment-related information. 

PMID- 25061664
TI  - Estimation of infiltration parameters and the irrigation coefficients with the
      surface irrigation advance distance.
AB  - A theory based on Manning roughness equation, Philip equation and water balance
      equation was developed which only employed the advance distance in the
      calculation of the infiltration parameters and irrigation coefficients in both
      the border irrigation and the surge irrigation. The improved procedure was
      validated with both the border irrigation and surge irrigation experiments. The
      main results are shown as follows. Infiltration parameters of the Philip equation
      could be calculated accurately only using water advance distance in the
      irrigation process comparing to the experimental data. With the calculated
      parameters and the water balance equation, the irrigation coefficients were also
      estimated. The water advance velocity should be measured at about 0.5 m to 1.0 m
      far from the water advance in the experimental corn fields. 

PMID- 25061666
TI  - Efficient CO2-reducing activity of NAD-dependent formate dehydrogenase from
      Thiobacillus sp. KNK65MA for formate production from CO2 gas.
AB  - NAD-dependent formate dehydrogenase (FDH) from Candida boidinii (CbFDH) has been
      widely used in various CO2-reduction systems but its practical applications are
      often impeded due to low CO2-reducing activity. In this study, we demonstrated
      superior CO2-reducing properties of FDH from Thiobacillus sp. KNK65MA (TsFDH) for
      production of formate from CO2 gas. To discover more efficient CO2-reducing FDHs
      than a reference enzyme, i.e. CbFDH, five FDHs were selected with biochemical
      properties and then, their CO2-reducing activities were evaluated. All FDHs
      including CbFDH showed better CO2-reducing activities at acidic pHs than at
      neutral pHs and four FDHs were more active than CbFDH in the CO2 reduction
      reaction. In particular, the FDH from Thiobacillus sp. KNK65MA (TsFDH) exhibited
      the highest CO2-reducing activity and had a dramatic preference for the reduction
      reaction, i.e., a 84.2-fold higher ratio of CO2 reduction to formate oxidation in
      catalytic efficiency (kcat/KB) compared to CbFDH. Formate was produced from CO2
      gas using TsFDH and CbFDH, and TsFDH showed a 5.8-fold higher formate production
      rate than CbFDH. A sequence and structural comparison showed that FDHs with
      relatively high CO2-reducing activities had elongated N- and C-terminal loops.
      The experimental results demonstrate that TsFDH can be an alternative to CbFDH as
      a biocatalyst in CO2 reduction systems. 

PMID- 25061668
TI  - Zinc(II) catalyzed conversion of alkynes to vinyl triflates in the presence of
      silyl triflates.
AB  - The conversion of alkynes to their corresponding vinyl triflates in the presence
      of stoichiometric TMS-triflate was greatly facilitated by the triflate salt of
      several transition metal catalysts most especially Zn(OTf)2. Products are formed
      in high regioselectivity under mild conditions. Internal alkynes bearing an aryl
      substituent afford vinyl triflates with a modest preference for the Z-isomer
      especially with larger substituents. A mechanism is put forward to explain the
      unique role of silicon in this system. 

PMID- 25061667
TI  - Diverse functions of mRNA metabolism factors in stress defense and aging of
      Caenorhabditis elegans.
AB  - Processing bodies (PBs) and stress granules (SGs) are related, cytoplasmic RNA
      protein complexes that contribute to post-transcriptional gene regulation in all
      eukaryotic cells. Both structures contain translationally repressed mRNAs and
      several proteins involved in silencing, stabilization or degradation of mRNAs,
      especially under environmental stress. Here, we monitored the dynamic formation
      of PBs and SGs, in somatic cells of adult worms, using fluorescently tagged
      protein markers of each complex. Both complexes were accumulated in response to
      various stress conditions, but distinct modes of SG formation were induced,
      depending on the insult. We also observed an age-dependent accumulation of PBs
      but not of SGs. We further showed that direct alterations in PB-related genes can
      influence aging and normal stress responses, beyond their developmental role. In
      addition, disruption of SG-related genes had diverse effects on development,
      fertility, lifespan and stress resistance of worms. Our work therefore underlines
      the important roles of mRNA metabolism factors in several vital cellular
      processes and provides insight into their diverse functions in a multicellular
      organism. 

PMID- 25061669
TI  - Bayesian spatial semi-parametric modeling of HIV variation in Kenya.
AB  - Spatial statistics has seen rapid application in many fields, especially
      epidemiology and public health. Many studies, nonetheless, make limited use of
      the geographical location information and also usually assume that the
      covariates, which are related to the response variable, have linear effects. We
      develop a Bayesian semi-parametric regression model for HIV prevalence data.
      Model estimation and inference is based on fully Bayesian approach via Markov
      Chain Monte Carlo (McMC). The model is applied to HIV prevalence data among men
      in Kenya, derived from the Kenya AIDS indicator survey, with n = 3,662. Past
      studies have concluded that HIV infection has a nonlinear association with age.
      In this study a smooth function based on penalized regression splines is used to
      estimate this nonlinear effect. Other covariates were assumed to have a linear
      effect. Spatial references to the counties were modeled as both structured and
      unstructured spatial effects. We observe that circumcision reduces the risk of
      HIV infection. The results also indicate that men in the urban areas were more
      likely to be infected by HIV as compared to their rural counterpart. Men with
      higher education had the lowest risk of HIV infection. A nonlinear relationship
      between HIV infection and age was established. Risk of HIV infection increases
      with age up to the age of 40 then declines with increase in age. Men who had STI
      in the last 12 months were more likely to be infected with HIV. Also men who had
      ever used a condom were found to have higher likelihood to be infected by HIV. A
      significant spatial variation of HIV infection in Kenya was also established. The
      study shows the practicality and flexibility of Bayesian semi-parametric
      regression model in analyzing epidemiological data. 

PMID- 25061670
TI  - The evolution of altruism in humans.
AB  - Humans are an intensely social species, frequently performing costly behaviors
      that benefit others. Efforts to solve the evolutionary puzzle of altruism have a
      lengthy history, and recent years have seen many important advances across a
      range of disciplines. Here we bring together this interdisciplinary body of
      research and review the main theories that have been proposed to explain human
      prosociality, with an emphasis on kinship, reciprocity, indirect reciprocity,
      punishment, and morality. We highlight recent methodological advances that are
      stimulating research and point to some areas that either remain controversial or
      merit more attention. 

PMID- 25061671
TI  - Multiple identities in social perception and interaction: challenges and
      opportunities.
AB  - Categorization plays a fundamental role in organizing daily interactions with the
      social world. However, there is increasing recognition that social categorization
      is often complex, both because category membership can be ambiguous (e.g.,
      multiracial or transgender identities) and because different categorical
      identities (e.g., race and gender) may interact to determine the meaning of
      category membership. These complex identities simultaneously impact social
      perceivers' impressions and social targets' own experiences of identity, thereby
      shaping perceptions, experiences, and interactions in fundamental ways. This
      review examines recent research on the perception and experience of the complex,
      multifaceted identities that both complicate and enrich our lives. Although
      research has historically tended to focus more on difficulties and challenges
      associated with multiple identities, increasing attention is being paid to
      opportunities that emerge from the possession of identities that include multiple
      distinct or overlapping groups. We consider how these opportunities might benefit
      both perceivers and targets. 

PMID- 25061672
TI  - Developmental flexibility in the age of globalization: autonomy and identity
      development among immigrant adolescents.
AB  - The socioeconomic and cultural changes that result from an increasingly
      interconnected world have been speculated to have important implications for the
      nature of adolescent development. Unfortunately, the historical time necessary
      for these changes to take place means that definitive research on the impact of
      globalization necessarily will be slow in forthcoming. Adolescents from immigrant
      families, however, already experience the social and cultural shifts thought to
      typify globalization, and an analysis of their experiences could shed light on
      what to expect as existing national barriers become more permeable. The value of
      flexibility in the face of great social and cultural change appears to be the
      dominant theme from research on immigrant youth, although that flexibility can be
      constrained by socioeconomic, ethnic, and racial stratification systems in host
      societies. This review highlights the implications of these findings for what may
      lie ahead for teenagers as globalization continues to expand. 

PMID- 25061673
TI  - Causality in thought.
AB  - Causal knowledge plays a crucial role in human thought, but the nature of causal
      representation and inference remains a puzzle. Can human causal inference be
      captured by relations of probabilistic dependency, or does it draw on richer
      forms of representation? This article explores this question by reviewing
      research in reasoning, decision making, various forms of judgment, and
      attribution. We endorse causal Bayesian networks as the best normative framework
      and as a productive guide to theory building. However, it is incomplete as an
      account of causal thinking. On the basis of a range of experimental work, we
      identify three hallmarks of causal reasoning-the role of mechanism, narrative,
      and mental simulation-all of which go beyond mere probabilistic knowledge. We
      propose that the hallmarks are closely related. Mental simulations are
      representations over time of mechanisms. When multiple actors are involved, these
      simulations are aggregated into narratives. 

PMID- 25061674
TI  - Interesting open questions in disease ecology and evolution.

PMID- 25061675
TI  - Infection dynamics in coexisting sexual and asexual host populations: support for
      the Red Queen hypothesis.
AB  - The persistence of sexual reproduction is a classic problem in evolutionary
      biology. The problem stems from the fact that, all else equal, asexual lineages
      should rapidly replace coexisting sexual individuals due to the cost of producing
      males in sexual populations. One possible countervailing advantage to sexual
      reproduction is that, on average, outcrossed offspring are more resistant than
      common clones to coevolving parasites, as predicted under the Red Queen
      hypothesis. In this study, we evaluated the prevalence of infection by a
      sterilizing trematode (Microphallus sp.) in a natural population of freshwater
      snails that was composed of both sexual and asexual individuals (Potamopyrgus
      antipodarum). More specifically, we compared the frequency of infection in sexual
      and asexual individuals over a 5-year period at four sites at a natural glacial
      lake (Lake Alexandrina, South Island, New Zealand). We found that at most sites
      and over most years, the sexual population was less infected than the coexisting
      asexual population. Moreover, the frequency of uninfected sexual females was
      periodically greater than two times the frequency of uninfected asexual females.
      These results give clear support for a fluctuating parasite-mediated advantage to
      sexual reproduction in a natural population.

PMID- 25061676
TI  - The ecology and evolution of animal medication: genetically fixed response versus
      phenotypic plasticity.
AB  - Animal medication against parasites can occur either as a genetically fixed
      (constitutive) or phenotypically plastic (induced) behavior. Taking the
      tritrophic interaction between the monarch butterfly Danaus plexippus, its
      protozoan parasite Ophryocystis elektroscirrha, and its food plant Asclepias spp.
      as a test case, we develop a game-theory model to identify the epidemiological
      (parasite prevalence and virulence) and environmental (plant toxicity and
      abundance) conditions that predict the evolution of genetically fixed versus
      phenotypically plastic forms of medication. Our model shows that the relative
      benefits (the antiparasitic properties of medicinal food) and costs (side effects
      of medicine, the costs of searching for medicine, and the costs of plasticity
      itself) crucially determine whether medication is genetically fixed or
      phenotypically plastic. Our model suggests that animals evolve phenotypic
      plasticity when parasite risk (a combination of virulence and prevalence and thus
      a measure of the strength of parasite-mediated selection) is relatively low to
      moderately high and genetically fixed medication when parasite risk becomes very
      high. The latter occurs because at high parasite risk, the costs of plasticity
      are outweighed by the benefits of medication. Our model provides a simple and
      general framework to study the conditions that drive the evolution of alternative
      forms of animal medication.

PMID- 25061677
TI  - The effect of immunodeficiency on the evolution of virulence: an experimental
      test with the rodent malaria Plasmodium chabaudi.
AB  - Host immunity plays an important role in the evolution of pathogen virulence and
      disease emergence. There is increasing theoretical and empirical evidence that
      enhanced immunity through vaccination may have the unfortunate side effect of
      selecting for more virulent parasites, but the effect of host immune suppression
      on pathogen evolution is less clear. Here, we use serial passage experiments in
      mice to test how immune-suppressed hosts may alter pathogen virulence evolution.
      We passaged Plasmodium chabaudi through CD4(+) T cell-depleted or control mice
      every 7 days for 20 weeks and then measured virulence differences during
      infection of immunologically normal mice. We found that those parasites that had
      been selected through CD4(+) T cell-depleted mice were more virulent than
      parasites selected through control mice. Virulence increases during serial
      passage are believed to be caused by pathogen adaptation to the passage host.
      These data suggest that immune-suppressed hosts could provide a within-host
      environment that lowers the barrier to parasite adaptation and promotes the
      evolution of virulence.

PMID- 25061678
TI  - Heritable, heterogeneous, and costly resistance of sheep against nematodes and
      potential feedbacks to epidemiological dynamics.
AB  - Infected hosts may preserve fitness by resisting parasites (reducing parasite
      burden) and/or tolerating them (preventing or repairing infection-induced
      damage). Theory predicts that these individual-level defense strategies generate
      divergent population-level feedbacks that would maintain genetic heterogeneity
      for resistance but purge heterogeneity for tolerance. Because resistance reduces
      parasite abundance, selection for costly resistance traits will weaken as
      resistance becomes common. Such negative frequency-dependent selection contrasts
      with predictions for tolerance, which maintains parasite abundance and so is
      expected to generate positive frequency-dependent selection, unless, for example,
      tolerance trades off with resistance. Thus far, there have been few tests of this
      theory in natural systems. Here, we begin testing the predictions in a mammalian
      field system, using data on individual gastrointestinal nematode burdens,
      nematode-specific antibody titers (as a resistance metric), the slope of body
      weight on parasite burden (as a tolerance metric), and fitness from an unmanaged
      population of Soay sheep. We find that nematode resistance is costly to fitness
      and underpinned by genetic heterogeneity, and that resistance is independent of
      tolerance. Drawing upon empirical metrics such as developed here, future work
      will elucidate how resistance and tolerance feedbacks interact to generate
      population-scale patterns in the Soay sheep and other field systems.

PMID- 25061679
TI  - Predators and patterns of within-host growth can mediate both among-host
      competition and evolution of transmission potential of parasites.
AB  - Parasite prevalence shows tremendous spatiotemporal variation. Theory indicates
      that this variation might stem from life-history characteristics of parasites and
      key ecological factors. Here, we illustrate how the interaction of an important
      predator and the schedule of transmission potential of two parasites can explain
      parasite abundance. A field survey showed that a noncastrating fungus
      (Metschnikowia bicuspidata) commonly infected a dominant zooplankton host
      (Daphnia dentifera), while a castrating bacterial parasite (Pasteuria ramosa) was
      rare. This result seemed surprising given that the bacterium produces many more
      infectious propagules (spores) than the fungus upon host death. The fungus's
      dominance can be explained by the schedule of within-host growth of parasites
      (i.e., how transmission potential changes over the course of infection) and the
      release of spores from "sloppy" predators (Chaoborus spp., who consume Daphnia
      prey whole and then later regurgitate the carapace and parasite spores). In
      essence, sloppy predators create a niche that the faster-schedule fungus
      currently occupies. However, a selection experiment showed that the slower
      schedule bacterium can evolve into this faster-schedule, predator-mediated niche
      (but pays a cost in maximal spore yield to do so). Hence, our study shows how
      parasite life history can interact with predation to strongly influence the
      ecology, epidemiology, and evolution of infectious disease.

PMID- 25061680
TI  - Bacteria-phage interactions across time and space: merging local adaptation and
      time-shift experiments to understand phage evolution.
AB  - The study of parasite local adaptation to host populations offers important
      insight into the spatial scale of host-parasite interactions. For parasites
      adapting to local hosts, the process is continually driven by change in the host
      population, in response to either the parasite or alternative selection
      pressures. In the case of reciprocal coevolutionary change, this adaptation
      should generate a pattern whereby parasites are most fit against hosts from the
      recent past (which have not yet responded to parasite-mediated selection) and
      least fit against future host populations (with increased resistance). I argue
      that combining data on local adaptation across space with data on evolutionary
      responses over time can offer novel insight into the process of adaptation. Using
      bacteriophages from horse chestnut trees, I compare infectivity on bacterial
      hosts isolated from either the same tree or different trees over multiple months
      of the growing season and find that phage adaptation to local hosts is most
      pronounced on bacterial hosts from the recent past. These results confirm that
      phages are well adapted to bacterial populations living within eukaryotes and
      more broadly suggest that local adaptation studies may underestimate the
      magnitude of parasite evolution, as host and parasite adaptation are confounded
      within contemporary time points.

PMID- 25061681
TI  - Experimental coevolution: rapid local adaptation by parasites depends on host
      mating system.
AB  - Host-parasite interactions can drive rapid, reciprocal genetic changes
      (coevolution), provided both hosts and parasites have high heritabilities for
      resistance/infectivity. Similarly, the host's mating system should also affect
      the rate of coevolutionary change in host-parasite interactions. Using
      experimental coevolution, we determined the effect of obligate outcrossing verses
      partial self-fertilization (mixed mating) on the rate of evolutionary change in a
      nematode host (Caenorhabditis elegans) and its bacterial parasite (Serratia
      marcescens). Bacterial populations were derived from a common ancestor. We
      measured the effects of host mating system on host adaptation to the parasite. We
      then determined the extent of parasite adaptation to their local host
      populations. Obligately outcrossing hosts exhibited more rapid adaptation to
      parasites than did mixed mating hosts. In addition, most of the parasites became
      adapted to infecting their local hosts, but parasites from obligately outcrossing
      hosts showed a greater level of local adaptation. These results suggest that host
      populations evolved along separate trajectories and that outcrossing host
      populations diverged further than partially selfing populations. Finally,
      parasites tracking outcrossing host populations diverged further than parasites
      tracking the partially selfing host populations. These results show that the
      evolutionary trajectories of both hosts and parasites can be shaped by the host's
      mating system.

PMID- 25061682
TI  - Baboons' response speed is biased by their moods.
AB  - The affect-as-information hypothesis (e.g., Schwarz & Clore, 2003), predicts that
      the positive or negative valence of our mood differentially affects our
      processing of the details of the environment. However, this hypothesis has only
      been tested with mood induction procedures and fairly complex cognitive tasks in
      humans. Here, six baboons (Papio papio) living in a social group had free access
      to a computerized visual search task on which they were over-trained. Trials that
      immediately followed a spontaneously expressed emotional behavior were analyzed,
      ruling out possible biases due to induction procedures. RTs following negatively
      valenced behaviors are slower than those following neutral and positively
      valenced behaviors, respectively. Thus, moods affect the performance of nonhuman
      primates tested in highly automatized tasks, as it does in humans during tasks
      with much higher cognitive demands. These findings reveal a presumably universal
      and adaptive mechanism by which moods influence performance in various ecological
      contexts. 

PMID- 25061683
TI  - Online community detection for large complex networks.
AB  - Complex networks describe a wide range of systems in nature and society. To
      understand complex networks, it is crucial to investigate their community
      structure. In this paper, we develop an online community detection algorithm with
      linear time complexity for large complex networks. Our algorithm processes a
      network edge by edge in the order that the network is fed to the algorithm. If a
      new edge is added, it just updates the existing community structure in constant
      time, and does not need to re-compute the whole network. Therefore, it can
      efficiently process large networks in real time. Our algorithm optimizes expected
      modularity instead of modularity at each step to avoid poor performance. The
      experiments are carried out using 11 public data sets, and are measured by two
      criteria, modularity and NMI (Normalized Mutual Information). The results show
      that our algorithm's running time is less than the commonly used Louvain
      algorithm while it gives competitive performance. 

PMID- 25061684
TI  - Diverse wild bird host range of Mycoplasma gallisepticum in eastern North
      America.
AB  - Emerging infectious diseases often result from pathogens jumping to novel hosts.
      Identifying possibilities and constraints on host transfer is therefore an
      important facet of research in disease ecology. Host transfers can be studied for
      the bacterium Mycoplasma gallisepticum, predominantly a pathogen of poultry until
      its 1994 appearance and subsequent epidemic spread in a wild songbird, the house
      finch Haemorhous mexicanus and some other wild birds. We screened a broad range
      of potential host species for evidence of infection by M. gallisepticum in order
      to answer 3 questions: (1) is there a host phylogenetic constraint on the
      likelihood of host infection (house finches compared to other bird species); (2)
      does opportunity for close proximity (visiting bird feeders) increase the
      likelihood of a potential host being infected; and (3) is there seasonal
      variation in opportunity for host jumping (winter resident versus summer resident
      species). We tested for pathogen exposure both by using PCR to test for the
      presence of M. gallisepticum DNA and by rapid plate agglutination to test for the
      presence of antibodies. We examined 1,941 individual birds of 53 species from 19
      avian families. In 27 species (15 families) there was evidence for exposure with
      M. gallisepticum although conjunctivitis was very rare in non-finches. There was
      no difference in detection rate between summer and winter residents, nor between
      feeder birds and species that do not come to feeders. Evidence of M.
      gallisepticum infection was found in all species for which at least 20
      individuals had been sampled. Combining the present results with those of
      previous studies shows that a diverse range of wild bird species may carry or
      have been exposed to M. gallisepticum in the USA as well as in Europe and Asia. 

PMID- 25061685
TI  - Enhanced photodynamic therapy and effective elimination of cancer stem cells
      using surfactant-polymer nanoparticles.
AB  - Photodynamic therapy is a potentially curative treatment for various types of
      cancer. It involves energy transfer from an excited photosensitizer to
      surrounding oxygen molecules to produce cytotoxic singlet oxygen species, a
      process termed as type II reaction. The efficiency of photodynamic therapy is
      greatly reduced because of the reduced levels of oxygen, often found in tumor
      microenvironments that also house cancer stem cells, a subpopulation of tumor
      cells that are characterized by enhanced tumorigenicity and resistance to
      conventional therapies. We show here that encapsulation of a photosensitizer,
      methylene blue, in alginate-Aerosol OT nanoparticles leads to an increased
      production of reactive oxygen species (ROS) under both normoxic and hypoxic
      conditions. ROS generation was found to depend on the interaction of the cationic
      photosensitizer with the anionic alginate polymer. Dye-polymer interaction was
      characterized by formation of methylene blue dimers, potentially enabling
      electron transfer and a type I photochemical reaction that is less sensitive to
      environmental oxygen concentration. We also find that nanoparticle encapsulated
      methylene blue has the capacity to eliminate cancer stem cells under hypoxic
      conditions, an important goal of current cancer therapy. 

PMID- 25061686
TI  - Development of a reference material of a single DNA molecule for the quality
      control of PCR testing.
AB  - We developed a reference material of a single DNA molecule with a specific
      nucleotide sequence. The double-strand linear DNA which has PCR target sequences
      at the both ends was prepared as a reference DNA molecule, and we named the PCR
      targets on each side as confirmation sequence and standard sequence. The highly
      diluted solution of the reference molecule was dispensed into 96 wells of a
      plastic PCR plate to make the average number of molecules in a well below one.
      Subsequently, the presence or absence of the reference molecule in each well was
      checked by real-time PCR targeting for the confirmation sequence. After an
      enzymatic treatment of the reaction mixture in the positive wells for the
      digestion of PCR products, the resultant solution was used as the reference
      material of a single DNA molecule with the standard sequence. PCR analyses
      revealed that the prepared samples included only one reference molecule with high
      probability. The single-molecule reference material developed in this study will
      be useful for the absolute evaluation of a detection limit of PCR-based testing
      methods, the quality control of PCR analyses, performance evaluations of PCR
      reagents and instruments, and the preparation of an accurate calibration curve
      for real-time PCR quantitation. 

PMID- 25061687
TI  - Development of [18F]-labeled pyrazolo[4,3-e]-1,2,4- triazolo[1,5-c]pyrimidine
      (SCH442416) analogs for the imaging of cerebral adenosine A2A receptors with
      positron emission tomography.
AB  - Cerebral adenosine A2A receptors (A2ARs) are attractive therapeutic targets for
      the treatment of neurodegenerative and psychiatric disorders. We developed high
      affinity and selective compound 8 (SCH442416) analogs as in vivo probes for A2ARs
      using PET. We observed the A2AR-mediated accumulation of [18F]fluoropropyl ([18F]
      10b) and [18F]fluoroethyl ([18F]-10a) derivatives of 8 in the brain. The striatum
      was clearly visualized in PET and in vitro autoradiography images of control
      animals and was no longer visible after pretreatment with the A2AR subtype
      selective antagonist KW6002. In vitro and in vivo metabolite analyses indicated
      the presence of hydrophilic (radio)metabolite(s), which are not expected to cross
      the blood-brain-barrier. [18F]-10b and [18F]-10a showed comparable striatum-to-
      cerebellum ratios (4.6 at 25 and 37 min post injection, respectively) and
      reversible binding in rat brains. We concluded that these compounds performed
      equally well, but their kinetics were slightly different. These molecules are
      potential tools for mapping cerebral A2ARs with PET.

PMID- 25061688
TI  - Sustained effects of a nurse coaching intervention via telehealth to improve
      health behavior change in diabetes.
AB  - BACKGROUND: Diabetes educators and self-management programs are scarce in rural
      communities, where diabetes is the third highest-ranking health concern. The goal
      of this study was to evaluate the benefits of nurse telehealth coaching for
      persons with diabetes living in rural communities through a person-centered
      approach using motivational interviewing (MI) techniques. MATERIALS AND METHODS:
      A randomized experimental study design was used to assign participants to receive
      either nurse telehealth coaching for five sessions (intervention group) or usual
      care (control group). Outcomes were measured in both groups using the Diabetes
      Empowerment Scale (DES), SF-12, and satisfaction surveys. Mean scores for each
      outcome were compared at baseline and at the 9-month follow-up for both groups
      using a Student's t test. We also evaluated the change from baseline by
      estimating the difference in differences (pre- and postintervention) using
      regression methods. RESULTS: Among the 101 participants included in the analysis,
      51 received nurse telehealth coaching, and 50 received usual care. We found
      significantly higher self-efficacy scores in the intervention group compared with
      the control group based on the DES at 9 months (4.03 versus 3.64, respectively;
      p<0.05) and the difference in difference estimation (0.42; p<0.05). CONCLUSIONS:
      The nurse MI/telehealth coaching model used in this study shows promise as an
      effective intervention for diabetes self-management in rural communities. The
      sustained effect on outcomes observed in the intervention group suggests that
      this model could be a feasible intervention for long-term behavioral change among
      persons living with chronic disease in rural communities.

PMID- 25061689
TI  - Cellular uptake and cytotoxicity of a near-IR fluorescent corrole-TiO2
      nanoconjugate.
AB  - We are investigating the biological and biomedical imaging roles and impacts of
      fluorescent metallocorrole-TiO2 nanoconjugates as potential near-infrared optical
      contrast agents in vitro in cancer and normal cell lines. The TiO2 nanoconjugate
      labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15
      tris(pentafluorophenyl)corrolato aluminum(III) (1-Al-TiO2) was prepared. The
      nanoparticle 1-Al-TiO2 was characterized by transmission electron microscopy
      (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of
      three different samples of TiO2 nanoparticles (bare, H2O2 etched, and 1-Al
      functionalized) showed similarity in shapes and sizes with an average diameter of
      29nm for 1-Al-TiO2. Loading of 1-Al on the TiO2 surfaces was determined to be ca.
      20-40mg 1-Al/g TiO2. Confocal fluorescence microscopy (CFM) studies of luciferase
      transfected primary human glioblastoma U87-Luc cells treated with the
      nanoconjugate 1-Al-TiO2 as the contrast agent in various concentrations were
      performed. The CFM images revealed that 1-Al-TiO2 was found inside the cancer
      cells even at low doses (0.02-2MUg/mL) and localized in the cytosol.
      Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al
      TiO2 showed minimal cytotoxic effects even at higher doses (2-2000MUg/mL) after
      24h. A similar observation was made using primary mouse hepatocytes (PMH) treated
      with 1-Al-TiO2 at low doses (0.0003-3MUg/mL). Longer incubation times (after 48
      and 72h for U87-Luc) and higher doses (>20MUg/mL 1-Al-TiO2 for U87-Luc and
      >3MUg/mL 1-Al-TiO2 for PMH) showed decreased cell viability. 

PMID- 25061690
TI  - Synthesis and properties of a new micellar polyphosphazene-platinum(II) conjugate
      drug.
AB  - Aiming at tumor targeting delivery of oxaliplatin using polymer therapy, a new
      monomeric platinum(II) complex (dach)Pt[HEDM] (dach: trans-(+/-)-1,2
      diaminocyclohexane; HEDM: 2-hydroxyethoxydiethylmalate) was designed to include
      the antitumor moiety (dach)Pt and HEDM as a linker to the polyphosphazene
      backbone. This monomeric Pt-complex could easily be grafted to the PEGylated
      polyphosphazene backbone to prepare a novel polyphosphazene-Pt conjugate,
      [NP(MPEG550)(dach)Pt(EM)]n [MPEG550: methoxy poly(ethylene glycol) with an
      average molecular weight of 550; EM: ethoxymalate]. This amphiphilic
      polyphosphazene-Pt conjugate was found to self-assemble into stable polymeric
      micelles of a mean diameter of 130nm, which is suitable for passive tumor
      targeting by enhanced permeability and retention (EPR) effect. Pharmacokinetic
      study of this polymer conjugate exhibited long blood circulation as expected and
      longer half-life (t1/2beta=9.52h) compared with oxaliplatin (3.47h), and much
      larger AUC (area under the curve) value (25,831ng.h/mL) compared with oxaliplatin
      (1194ng.h/mL). Biodistribution study of the polymer conjugate has shown excellent
      tumor selectivity with the tumor to tissue ratio of 3.84 at 2h post injection and
      11.7 at 24h post injection probably due to the EPR effect of the polymer
      conjugate while no tumor selectivity was observed for monomeric oxaliplatin.
      Furthermore, accumulation of this polymer conjugate in kidney was much lower
      compared with oxaliplatin. Also the nude mouse xenograft trial of the polymer
      conjugate has shown higher antitumor efficacy compared with oxaliplatin. 

PMID- 25061691
TI  - Synthesis, characterization and binding affinities of rhenium(I)
      thiosemicarbazone complexes for the estrogen receptor (alpha/beta).
AB  - The binding affinities towards estrogen receptors (ERs) alpha and beta of a set
      of thiosemicarbazone ligands (HL(n)) and their rhenium(I) carbonyl complexes
      [ReX(HL(n))(CO)3] (X=Cl, Br) were determined by a competitive standard
      radiometric assay with [(3)H]-estradiol. The ability of the coordinated
      thiosemicarbazone ligands to undergo deprotonation and the lability of the ReX
      bond were used as a synthetic strategy to obtain [Re(hpy)(L(n))(CO)3] (hpy=3- or
      4-hydroxypyridine). The inclusion of the additional hpy ligand endows the new
      thiosemicarbazonate complexes with an improved affinity towards the estrogen
      receptors and, consequently, the values of the inhibition constant (Ki) could be
      determined for some of them. In general, the values of Ki for both ER subtypes
      suggest an appreciable selectivity towards ERalpha.

PMID- 25061692
TI  - Factors affecting the presence of human-associated and fecal indicator real-time
      quantitative PCR genetic markers in urban-impacted recreational beaches.
AB  - Urban runoff can carry a variety of pollutants into recreational beaches, often
      including bacterial pathogens and indicators of fecal contamination. To develop
      complete recreational criteria and risk assessments, it is necessary to
      understand conditions under which human contamination could be present at beaches
      solely impacted by urban runoff. Accurately estimating risk requires
      understanding sources, concentrations, and transport mechanisms of microbial
      contaminants in these environments. By applying microbial source tracking methods
      and empirical modeling, we assessed the presence and level of human contamination
      at urban runoff impacted recreational beaches. We also identified environmental
      parameters and pollution sources that can influence the concentration and
      transport of culturable and molecular fecal indicator bacteria (FIB) in systems
      impacted solely by urban runoff. Water samples and physico-chemical parameters
      were collected from shoreline locations from three South Carolina (SC) beaches
      (five locations per beach) and two Florida (FL) beaches (three locations per
      beach). Each SC beach was directly impacted by swashes or tidal creeks receiving
      stormwater runoff from the urbanized area and therefore were designated as swash
      drain associated (SDA) beaches, while FL beaches were designated as non-swash
      drain associated (NSDA). Sampling in swash drains (SD; three sites per SD)
      directly impacting each SC beach was also conducted. Results indicate that
      although culturable (enterococci) and real-time quantitative polymerase chain
      reaction (qPCR) (EC23S857, Entero1, and GenBac3) FIB concentrations were, on
      average, higher at SD locations, SDA beaches did not have consistently higher
      molecular FIB signals compared to NSDA beaches. Both human-associated markers
      (HF183 and HumM2) were concomitantly found only at SDA beaches. Bacteroidales
      species-specific qPCR markers (BsteriF1 and BuniF2) identified differences in the
      Bacteroidales community, depending on beach type. The marker for general
      Bacteroidales was most abundant at SD locations and exhibited a high correlation
      with both culturable and other molecular markers. Combining molecular information
      with predictive modeling allowed us to identify both alongshore movement of
      currents and SD outflow as significant influences on the concentration of
      molecular and culturable indicators in the bathing zone. Data also suggests that
      combining methodologies is a useful and cost effective approach to help
      understand transport dynamics of fecal contamination and identify potential
      sources of contamination at marine beaches. 

PMID- 25061693
TI  - The impacts of wind power integration on sub-daily variation in river flows
      downstream of hydroelectric dams.
AB  - Due to their operational flexibility, hydroelectric dams are ideal candidates to
      compensate for the intermittency and unpredictability of wind energy production.
      However, more coordinated use of wind and hydropower resources may exacerbate the
      impacts dams have on downstream environmental flows, that is, the timing and
      magnitude of water flows needed to sustain river ecosystems. In this paper, we
      examine the effects of increased (i.e., 5%, 15%, and 25%) wind market penetration
      on prices for electricity and reserves, and assess the potential for altered
      price dynamics to disrupt reservoir release schedules at a hydroelectric dam and
      cause more variable and unpredictable hourly flow patterns (measured in terms of
      the Richards-Baker Flashiness (RBF) index). Results show that the greatest
      potential for wind energy to impact downstream flows occurs at high (~25%) wind
      market penetration, when the dam sells more reserves in order to exploit spikes
      in real-time electricity prices caused by negative wind forecast errors.
      Nonetheless, compared to the initial impacts of dam construction (and the dam's
      subsequent operation as a peaking resource under baseline conditions) the
      marginal effects of any increased wind market penetration on downstream flows are
      found to be relatively minor. 

PMID- 25061694
TI  - Nanoscale electrocatalysis: visualizing oxygen reduction at pristine, kinked, and
      oxidized sites on individual carbon nanotubes.
AB  - There is a prevailing and widely adopted view that carbon nanotubes, which are
      finding considerable application in energy, healthcare, and electronics
      applications, are highly (electro)catalytically inert unless modified, doped, or
      defected. By visualizing the electrochemical reduction of oxygen (hydrogen
      peroxide generation) at high resolution along pristine (defect-free) regions of
      individual single-walled carbon nanotubes, we show that there is, in fact,
      significant activity comparable to that of standard gold electrocatalysts.
      Moreover, the activity is greatly enhanced at strained (kinked) sites and regions
      modified by oxidation. Single-walled carbon nanotubes are thus effective
      electrocatalysts in their own right and not just supports for other materials. 

PMID- 25061695
TI  - Constrained bithiazoles: small molecule correctors of defective DeltaF508-CFTR
      protein trafficking.
AB  - Conformationally constrained bithiazoles were previously found to have improved
      efficacy over nonconstrained bithiazoles for correction of defective cellular
      processing of the DeltaF508 mutant cystic fibrosis transmembrane conductance
      regulator (CFTR) protein. In this study, two sets of constrained bithiazoles were
      designed, synthesized, and tested in vitro using DeltaF508-CFTR expressing
      epithelial cells. The SAR data demonstrated that modulating the constraining ring
      size between 7- versus 8-membered in these constrained bithiazole correctors did
      not significantly enhance their potency (IC50), but strongly affected maximum
      efficacy (Vmax), with constrained bithiazoles 9e and 10c increasing Vmax by 1.5
      fold compared to benchmark bithiazole corr4a. The data suggest that the 7- and 8
      membered constrained ring bithiazoles are similar in their ability to accommodate
      the requisite geometric constraints during protein binding. 

PMID- 25061696
TI  - Levofloxacin-resistant haemophilus influenzae, Taiwan, 2004-2010.
AB  - Levofloxacin resistance in Haemophilus influenzae has increased significantly in
      Taiwan, from 2.0% in 2004 to 24.3% in 2010 (p<0.001). Clinical and molecular
      investigations of 182 levofloxacin-resistant isolates revealed that the increase
      was mainly the result of the spread of several clones in the elderly population
      in different regions. 

PMID- 25061697
TI  - Yersinia pestis in Pulex irritans fleas during plague outbreak, Madagascar.

PMID- 25061698
TI  - New introductions of enterovirus 71 subgenogroup C4 strains, France, 2012.
AB  - In France during 2012, human enterovirus 71 (EV-A71) subgenogroup C4 strains were
      detected in 4 children hospitalized for neonatal fever or meningitis.
      Phylogenetic analysis showed novel and independent EV-A71 introductions,
      presumably from China, and suggested circulation of C4 strains throughout France.
      This observation emphasizes the need for monitoring EV-A71 infections in Europe. 

PMID- 25061700
TI  - Evaluation of thermal antinociceptive effects after intramuscular administration
      of buprenorphine hydrochloride to American kestrels (Falco sparverius).
AB  - OBJECTIVE: To evaluate the thermal antinociceptive effects and duration of action
      of buprenorphine hydrochloride after IM administration to American kestrels
      (Falco sparverius). ANIMALS: 12 healthy 3-year-old American kestrels. PROCEDURES:
      Buprenorphine hydrochloride (0.1, 0.3, and 0.6 mg/kg) and a control treatment
      (saline [0.9% NaCl] solution) were administered IM in a randomized crossover
      experimental design. Foot withdrawal response to a thermal stimulus was
      determined 1 hour before (baseline) and 1.5, 3, and 6 hours after treatment
      administration. Agitation-sedation scores were determined 3 to 5 minutes before
      each thermal stimulus. Adverse effects were monitored for 6 hours after treatment
      administration. RESULTS: Buprenorphine hydrochloride at 0.1, 0.3, and 0.6 mg/kg,
      IM, increased thermal threshold for 6 hours, compared with the response for the
      control treatment. There were no significant differences among buprenorphine
      treatments. A mild sedative effect was detected at a dose of 0.6 mg of
      buprenorphine/kg. CONCLUSION AND CLINICAL RELEVANCE: At the doses tested,
      buprenorphine hydrochloride resulted in thermal antinociception in American
      kestrels for at least 6 hours, which suggested that buprenorphine has analgesic
      effects in this species. Further studies with longer evaluation periods and
      additional forms of noxious stimuli, formulations, dosages, and routes of
      administration are needed to fully evaluate the analgesic effects of
      buprenorphine in American kestrels.

PMID- 25061701
TI  - Pharmacokinetics of buprenorphine hydrochloride following intramuscular and
      intravenous administration to American kestrels (Falco sparverius).
AB  - OBJECTIVE: To determine the pharmacokinetics of buprenorphine hydrochloride after
      IM and IV administration to American kestrels (Falco sparverius). ANIMALS: 13
      healthy 3-year-old captive-bred American kestrels. PROCEDURES: Buprenorphine
      hydrochloride (0.6 mg/kg) was administered IM to all birds. Blood samples were
      collected at 9 times, ranging from 5 minutes to 9 hours after drug
      administration. Plasma buprenorphine concentrations were measured by use of
      tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were
      determined by use of least squares linear regression and noncompartmental
      analysis of naive pooled data. After a washout period of 2 weeks, the same dose
      of buprenorphine was administered IV to all birds and blood samples were
      collected at the same times after drug administration. RESULTS: Maximum plasma
      buprenorphine concentration was achieved within 5 minutes after IM
      administration. For IM administration, bioavailability was 94.8% and elimination
      half-life was 92.1 minutes. For IV administration, steady-state volume of
      distribution was 4,023.8 mL/kg, plasma clearance was 49.2 mL/min/kg, and
      elimination half-life was 105.5 minutes. CONCLUSIONS AND CLINICAL RELEVANCE:
      Buprenorphine was rapidly absorbed, and bioavailability was good after IM
      administration to American kestrels. Plasma buprenorphine concentrations were > 1
      ng/mL for 9 hours after both IM and IV administration. These results, in
      combination with those of a pharmacodynamic study, suggested that the analgesic
      effects of buprenorphine could last at least 6 to 9 hours in this species.
      Further investigations of the duration of analgesic effects, multiple-dose
      protocols, and potential adverse effects of buprenorphine are warranted in
      American kestrels and other raptors.

PMID- 25061702
TI  - Pharmacokinetics and pharmacodynamics of a constant rate infusion of fentanyl (5
      MUg/kg/h) in awake cats.
AB  - OBJECTIVE: To evaluate the pharmacokinetics and thermal and mechanical
      antinociceptive effects of a fentanyl constant rate infusion (CRI) in conscious
      cats. ANIMALS: 8 healthy adult cats. PROCEDURES: At a >= 14-day interval, 7 cats
      received a loading dose (LD) of fentanyl (5 MUg/kg, IV [administered at 0 hours])
      followed by fentanyl infusion (5 MUg/kg/h, IV) for 2 hours or similar
      administrations of equivalent volumes of 0.9% saline (NaCl) solution. One cat
      received only the fentanyl treatment. For both treatments, sedation and adverse
      events were evaluated and mechanical threshold (MT) and thermal threshold (TT)
      testing was performed prior to (baseline) and at predetermined times up to 26
      hours after LD administration; plasma fentanyl concentrations were determined at
      similar times when the cats received fentanyl. RESULTS: Fentanyl induced mild
      sedation during the infusion. The only adverse effect associated with fentanyl LD
      administration was profuse salivation (1 cat). Saline solution administration did
      not significantly change MT or TT over time. For the duration of the CRI, MT and
      TT differed significantly between treatments, except for TT 1 hour after LD
      administration. For the fentanyl treatment, MT and TT were significantly higher
      than baseline at 0.25 to 0.75 hours and at 0.25 to 1 hour, respectively. During
      the fentanyl CRI, mean +/- SD plasma fentanyl concentration decreased from 4.41
      +/- 1.86 ng/mL to 2.99 +/- 1.28 ng/mL and was correlated with antinociception;
      plasma concentrations < 1.33 +/- 0.30 ng/mL were not associated with
      antinociception. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl CRI (5 MUg/kg/h)
      induced mechanical and thermal antinociception in cats.

PMID- 25061703
TI  - Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial
      fluid of horses with osteochondral injury.
AB  - OBJECTIVE: To determine whether stromal cell-derived factor-1 (SDF-1)
      concentrations in serum, plasma, and synovial fluid differed among untrained,
      race-trained, and osteochondral-injured Thoroughbred racehorses. ANIMALS: 22
      racehorses without osteochondral injury and 37 racehorses with osteochondral
      injury. PROCEDURES: Horses without osteochondral injury were examined before and
      after 5 to 6 months of race training. Horses with osteochondral injury were
      undergoing arthroscopic surgery for removal of osteochondral fragments from
      carpal or metacarpophalangeal or metatarsophalangeal joints (fetlock joints).
      Serum, plasma, and fetlock or carpal synovial fluid samples were obtained and
      analyzed for SDF-1 concentration by use of an ELISA. RESULTS: In horses with
      fetlock or carpal joint injury, mean synovial fluid SDF-1 concentrations were
      significantly higher, serum SDF-1 concentrations were significantly lower, and
      synovial fluid-to-serum SDF-1 ratios were significantly higher than in untrained
      and trained horses. Synovial fluid SDF-1 concentrations were not significantly
      different between trained and untrained horses. Plasma SDF-1 concentrations were
      not different among the 3 groups. Results obtained with serum, compared with
      synovial fluid and plasma, had better sensitivity for differentiating between
      osteochondral-injured horses and uninjured horses. In horses with fetlock joint
      osteochondral injury, serum SDF-1 concentrations were correlated with
      radiographic and arthroscopic inflammation scores, but not arthroscopic cartilage
      scores. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that serum SDF-1
      concentrations were more sensitive than plasma and synovial fluid concentrations
      for detection of osteochondral injury in the fetlock or carpal joint of
      racehorses. Analysis of serum and synovial SDF-1 concentrations in horses with
      experimentally induced joint injury may help define the onset and progression of
      post-traumatic osteoarthritis and aid in the evaluation of anti-inflammatory
      treatments.

PMID- 25061704
TI  - Evaluation of tranexamic acid and epsilon-aminocaproic acid concentrations
      required to inhibit fibrinolysis in plasma of dogs and humans.
AB  - OBJECTIVE: To determine minimum plasma concentrations of the antifibrinolytic
      agents tranexamic acid (TEA) and epsilon-aminocaproic acid (EACA) needed to
      completely inhibit fibrinolysis in canine and human plasma after induction of
      hyperfibrinolysis. SAMPLES: Pooled citrated plasma from 7 dogs and commercial
      pooled citrated human plasma. PROCEDURES: Concentrations of EACA from 0 MUg/mL to
      500 MUg/mL and of TEA from 0 MUg/mL to 160 MUg/mL were added to pooled citrated
      canine and human plasma. Hyperfibrinolysis was induced with 1,000 units of tissue
      plasminogen activator/mL, and kaolin-activated thromboelastography was performed
      in duplicate. The minimum concentrations required to completely inhibit
      fibrinolysis 30 minutes after maximum amplitude of the thromboelastography
      tracing occurred were determined. RESULTS: Minimum plasma concentrations
      necessary for complete inhibition of fibrinolysis by EACA and TEA in pooled
      canine plasma were estimated as 511.7 MUg/mL (95% confidence interval [CI], 433.2
      to 590.3 MUg/mL) and 144.7 MUg/mL (95% CI, 125.2 to 164.2 MUg/mL), respectively.
      Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis
      in pooled human plasma were estimated as 122.0 MUg/mL (95% CI, 106.2 to 137.8
      MUg/mL) and 14.7 MUg/mL (95% CI, 13.7 to 15.6 MUg/mL), respectively. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results supported the concept that dogs are
      hyperfibrinolytic, compared with humans. Higher doses of EACA and TEA may be
      required to fully inhibit fibrinolysis in dogs.

PMID- 25061705
TI  - Comparison of air sac volume, lung volume, and lung densities determined by use
      of computed tomography in conscious and anesthetized Humboldt penguins
      (Spheniscus humboldti) positioned in ventral, dorsal, and right lateral
      recumbency.
AB  - OBJECTIVE: To determine the effects of recumbency on air sac volume, lung volume,
      and lung densities in CT images of healthy, conscious and anesthetized
      spontaneously breathing Humboldt penguins (Spheniscus humboldti). ANIMALS: 25
      adult (13 male and 12 female) Humboldt penguins. PROCEDURES: CT images of
      conscious penguins in ventral recumbency and anesthetized penguins in dorsal,
      ventral, and right lateral recumbency were obtained. Air sac volume, lung volume,
      and lung densities in CT images were calculated. A paired samples t test was used
      to determine whether right and left lung densities differed among recumbencies.
      Repeated-measures ANOVA (controlled for sex and order of recumbencies during CT)
      was used to determine whether air sac or lung volumes differed among
      recumbencies. RESULTS: Recumbency had a significant effect on air sac volume but
      not lung volume. Air sac volume was largest in conscious penguins in ventral
      recumbency (mean +/- SD, 347.2 +/- 103.1 cm(3)) and lowest in anesthetized
      penguins in dorsal recumbency (median, 202.0 cm(3); 10th to 90th percentile,
      129.2 to 280.3 cm(3)). Lung densities were highest in anesthetized penguins in
      dorsal recumbency (right lung median, 0.522 g/cm(3); left lung median, 0.511
      g/cm(3)) and lowest in anesthetized penguins in ventral recumbency (right lung
      median, 0.488 g/cm(3); left lung median, 0.482 g/cm(3)). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that anesthetized Humboldt penguins had the lowest
      air sac volume and highest lung densities in dorsal recumbency. Therefore, this
      recumbency may not be recommended. Minimal changes in lung volume were detected
      among recumbencies or between conscious and anesthetized penguins.

PMID- 25061706
TI  - Expression of apical junction complex proteins in duodenal mucosa of dogs with
      inflammatory bowel disease.
AB  - OBJECTIVE: To determine the expression of tight junction and adherens junction
      proteins in duodenal mucosa samples of dogs with inflammatory bowel disease
      (IBD). ANIMALS: 12 dogs with IBD and 6 healthy control Beagles. PROCEDURES:
      Duodenal mucosa biopsy samples were endoscopically obtained from dogs with IBD
      and healthy control Beagles. The expression of claudin-1, -2, -3, -4, -5, -7, and
      -8; E-cadherin; and beta-catenin in the duodenal mucosa samples was determined by
      means of immunoblotting. The subcellular localization of E-cadherin in the
      duodenal mucosa samples was determined with immunofluorescence microscopy.
      RESULTS: The expression of each claudin and beta-catenin was not significantly
      different between control dogs and dogs with IBD. However, expression of E
      cadherin was significantly lower in duodenal mucosa samples of dogs with IBD than
      it was in samples obtained from healthy control dogs. Results of
      immunofluorescence microscopy indicated decreased intensity of E-cadherin
      labeling in the tips of villi in duodenal mucosa samples obtained from 6 dogs
      with IBD, compared with staining intensity for other dogs. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results of this study indicated expression of claudin-1, -2, 
      3, -4, -5, -7, and -8 and beta-catenin was not significantly different between
      duodenal mucosa samples obtained from control dogs and those obtained from dogs
      with IBD. However, E-cadherin expression was significantly lower in the villus
      epithelium in duodenal mucosa samples obtained from dogs with IBD versus samples
      obtained from control dogs, which suggested that decreased expression of that
      protein has a role in the pathogenesis of IBD in dogs.

PMID- 25061707
TI  - Modulation of growth and immunity by dietary supplementation with resveratrol in
      young chickens receiving conventional vaccinations.
AB  - OBJECTIVE: To determine the effects of resveratrol (RES) on growth and immune
      status in chickens receiving conventional vaccinations. ANIMALS: Two hundred
      forty 1-day-old layer chickens. PROCEDURES: Chickens received conventional
      vaccinations throughout the study and were randomly assigned to 1 of 4 treatments
      in 6 replicate pens/treatment. Treatments included 1 control group (basal diet)
      and 3 experimental groups fed the basal diet plus 200, 400, and 800 mg of RES/kg
      of diet. At 40 days of age, 1 bird/pen was randomly selected to have blood and
      tissues collected to determine serum immunity indices; mRNA relative expression
      of proinflammatory cytokines in splenocytes; mRNA relative expression of nuclear
      transcription factor-kappaB, growth hormone receptor, and insulin-like growth
      factor-1 in hepatocytes; cell proliferation; and apoptosis. RESULTS: Average
      daily gain, antibody titers against Newcastle disease virus and avian influenza
      viruses H5 and H9, and insulin-like growth factor-1 expression were quadratically
      increased with increasing RES concentration. In hepatocytes, growth hormone
      receptor gene mRNA relative expression was quadratically increased and nuclear
      transcription factor-kappaB gene mRNA relative expression was linearly decreased
      with increasing RES concentration. In splenocytes, nterleukin-1beta and tumor
      necrosis factor-alpha mRNA relative expression was linearly decreased with
      increasing RES concentration. Resveratrol supplementation delayed cell
      proliferation and reduced apoptosis in immunocytes. With increasing RES
      concentration, proliferation index and relative weight of the thymus, ratio of
      CD4+ to CD8+ cells, and CD4+ cell count were quadratically increased, and IgM
      concentration was linearly increased. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary
      resveratrol supplementation improved growth, protected immunocytes against
      antigen-induced apoptosis, and upregulated immune response in chickens that
      received conventional vaccinations.

PMID- 25061708
TI  - Effects of clopidogrel on horses with experimentally induced endotoxemia.
AB  - OBJECTIVE: To evaluate the effects of clopidogrel on clinical and
      clinicopathologic variables in healthy horses with experimentally induced
      endotoxemia. ANIMALS: 12 adult mares. Procedures-Horses were assigned with a
      randomization procedure to receive clopidogrel (4 mg/kg, once, then 2 mg/kg, q 24
      h; n = 6) or a placebo (6) through a nasogastric tube. After 72 hours of
      treatment, horses received lipopolysaccharide (LPS; 30 ng/kg, IV). Heart rate,
      respiratory rate, rectal temperature, CBC variables, plasma fibrinogen
      concentration, serum tumor necrosis factor-alpha concentration, plasma von
      Willebrand factor concentration, and measures of platelet activation (including
      ADP- and collagen-induced platelet aggregation and closure times,
      thrombelastography variables, and results of flow cytometric detection of
      platelet membrane P-selectin, phosphatidylserine, and microparticles) were
      determined at various times before and after LPS administration by investigators
      unaware of the treatment groups. Statistical analyses were performed with
      repeated-measures ANOVA. RESULTS: 4 of 6 clopidogrel-treated horses had
      significant decreases in ADP-induced platelet aggregation before and after LPS
      administration. Heart rate increased significantly after LPS administration only
      for the placebo group. No significant differences were detected between groups
      for CBC variables, closure time, and plasma concentration of fibrinogen or serum
      concentration of tumor necrosis factor-alpha, and no clinically relevant
      differences were detected for other hemostatic variables. CONCLUSIONS AND
      CLINICAL RELEVANCE: In this study, administration of LPS did not induce platelet
      hyperreactivity in horses on the basis of measures of platelet adhesion,
      aggregation, degranulation, and procoagulant activity. Administration of
      clopidogrel was associated with variable platelet antiaggregatory activity and
      attenuated some clinical signs of endotoxemia.

PMID- 25061709
TI  - Efficacy of a multivalent modified-live virus vaccine containing a Mannheimia
      haemolytica toxoid in calves challenge exposed with Bibersteinia trehalosi.
AB  - OBJECTIVE: To determine the efficacy of a multivalent modified-live virus (MLV)
      vaccine containing a Mannheimia haemolytica toxoid to reduce pneumonia and
      mortality rate when administered to calves challenge exposed with virulent
      Bibersteinia trehalosi. Animals-74 Holstein calves. PROCEDURES: Calves were
      assigned to 2 treatment groups. Calves in the control group (n = 36) were
      vaccinated by SC administration of 2 mL of a commercial 5-way MLV vaccine, and
      calves in the other group (38) were vaccinated by SC administration of a 2-mL
      dose of a 5-way MLV vaccine containing M haemolytica toxoid (day 0). On day 21,
      calves were transtracheally administered B trehalosi. Serum was obtained for
      analysis of antibody titers against M haemolytica leukotoxin. Nasopharyngeal swab
      specimens were collected from calves 1 day before vaccination (day -1) and
      challenge exposure (day 20) and cultured to detect bacterial respiratory
      pathogens. Clinical scores, rectal temperature, and death attributable to the
      challenge-exposure organism were recorded for 6 days after challenge exposure.
      Remaining calves were euthanized at the end of the study. Necropsy was performed
      on all calves, and lung lesion scores were recorded. RESULTS: Calves vaccinated
      with the MLV vaccine containing M haemolytica toxoid had significantly lower lung
      lesion scores, mortality rate, and clinical scores for respiratory disease,
      compared with results for control calves. CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of a multivalent MLV vaccine containing M haemolytica toxoid
      protected calves against challenge exposure with virulent B trehalosi by reducing
      the mortality rate, lung lesion scores, and clinical scores for respiratory
      disease.

PMID- 25061710
TI  - Strongly conjugated hydroporphyrin dyads: extensive modification of
      hydroporphyrins' properties by expanding the conjugated system.
AB  - We report the synthesis and basic photophysical characterization of strongly
      conjugated hydroporphyrin (chlorin and bacteriochlorin) dyads. Hydroporphyrins
      are connected at their respective 13 (beta) or 15 (meso) positions by ethynyl or
      butadiynyl linkers. Synthesis entails a series of palladium-catalyzed reactions,
      starting from appropriate bromobacteriochlorin or bromochlorin. Strong
      conjugation in the dyads results in a significant bathochromic shift of longest
      wavelength (Qy-like) band, which in case of the 13-13' ethynyl-linked
      bacteriochlorin dyad is positioned past 800 nm. The Qy-like band is broad and
      split for the 13-13' linked chlorin and bacteriochlorin dyads. All dyads exhibit
      an intense, relatively narrow fluorescence emission band in nonpolar solvents.
      Bacteriochlorin dyads exhibit a strong dependence of fluorescence intensity on
      the solvent polarity, which results in more than 10-fold quenching of
      fluorescence in dimethylformamide. The assembling of hydroporphyrins into
      strongly conjugated arrays represents an efficient means to tune and expand their
      optical and photochemical properties, which should greatly broaden the properties
      attainable for these chromophores. 

PMID- 25061711
TI  - Medial temporal lobe atrophy in Alzheimer's disease/mild cognitive impairment
      with depression.
AB  - OBJECTIVE: Depression is common in patients with Alzheimer's disease (AD) and
      mild cognitive impairment (MCI). Patients with depression have an earlier onset
      and rapid progression of cognitive decline. Medial temporal lobe atrophy (MTA) is
      common in AD and MCI, and some degree of atrophy is found in almost all patients.
      In the present study, an attempt was made to know if MTA is more common in
      patients with AD/MCI with depression than those without it. METHODS: Patients
      reporting to the outpatient department of a neurology centre of a tertiary care
      hospital were recruited for the present study. After initial general physical and
      neurological examination, they were evaluated using National Institute of
      Neurological and Communicative Disorders and Stroke and Related Disorders
      Association criteria for diagnosis of AD. Clinical Dementia rating scale was used
      for the diagnosis of MCI. Cornell scale for depression in dementia (CSDD) was
      used. RESULTS: We found 20 cases with depression as per CSDD out of a sample of
      37 patients (male:female = 30:7). There were 26 patients with AD and 11 with MCI.
      The mean age of all patients was 72.33 +/- 6.45 years. The mean mini mental
      status examination score was 19.00 +/- 6.73. The mean time since diagnosis was
      4.19 +/- 3.26 years. The mean Scheltens visual rating scale score for right MTA
      was 2.08 +/- 0.95 and was 2.05 +/- 0.94 for the left. Both scores did not differ
      statistically when analyzed using paired t-test (p > 0.05). However, difference
      in those with depression (2.36 +/- 0.95) from those without depression (1.60 +/-
      0.74) was significant (p < 0.05). CONCLUSION: MTA scores were higher in those
      with AD/MCI with depression than those without it.

PMID- 25061712
TI  - Effective 2D-RPLC/RPLC enrichment and separation of micro-components from
      Hedyotis diffusa Willd. and characterization by using ultra-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry.
AB  - An effective method aiming at enrichment and analysis of micro-components in
      traditional Chinese medicine (TCM) was developed. One fraction (fraction E) from
      the extract of Hedyotis diffusa Willd. was selected as test sample, which was
      isolated by using the XAD-4 macroporous resin. To study the micro-components, a
      two-dimensional reverse-phase liquid chromatography (2D-RPLC/RPLC) method was
      developed, comprising Click OEG and C18 stationary phases as the first and second
      dimensions, respectively. Of the eight sub-fractions isolated from the first
      dimension, three sub-fractions (fractions II-IV) containing micro-components were
      further separated with the second dimension. The 2D-RPLC/RPLC system was proved
      to possess high orthogonality. Furthermore, the micro-components were
      characterized by using ultra-performance liquid chromatography-diode array
      detector/quadrupole time-of-flight mass spectrometry (UPLC-DAD/Q-TOF MS) with
      electrospray ionization (ESI) source. With the optimized separation and
      characterization method, a large number (>400) of micro-components were enriched
      and detected from the extracts of H. diffusa Willd., the majority of which has
      not been isolated from the herb before. Among these isolated micro-components, 38
      compounds involving 24 phenylpropanoids, 7 flavonoids and 7 iridoid glucosides
      (IGs), were identified or tentatively identified from the H. diffusa extracts on
      the basis of spectral data of the authentic standards and the fragmentation
      characteristics information available in literatures. The proposed method made it
      possible to effectively screen and analyze the micro-components in TCMs or other
      complex natural medicines. 

PMID- 25061713
TI  - Comparative analysis of main aromatic acids and phthalides in Angelicae Sinensis
      Radix, Chuanxiong Rhizoma, and Fo-Shou-San by a validated UHPLC-TQ-MS/MS.
AB  - Fo-Shou-San (FSS) is an ancient and classic formula comprised of Angelicae
      Sinensis Radix (Danggui, DG) and Chuanxiong Rhizoma (Chuanxiong, CX) in a weight
      ratio of 3:2 with nourishing blood and dissipating blood stasis activities for
      the treatment of blood deficiency and blood stasis. In this study, a ultra-high
      performance liquid chromatography coupled with a triple quadrupole electrospray
      tandem mass spectrometry (UHPLC-TQ-MS/MS) method was developed for simultaneous
      quantification of three aromatic acids (chlorogenic acid, caffeic acid, ferulic
      acid) and six phthalides (senkyunolide I, senkyunolide H, senkyunolide A,
      butylphthalide, ligustilide and butylidenephthalide) in DG, CX and FSS. The nine
      components were simultaneously determined within 10min. The proposed method was
      fully validated in terms of linearity, sensitivity, precision, repeatability as
      well as recovery. The results showed that there were significant differences in
      their contents of DG and CX, and there were remarkable differences between the
      theorized content and observed content in FSS. The content of each component in
      formulae was not just the simple addition among its content in the single herbs.
      These research results might be helpful to illustrate the drug interactions
      during decocting process of herb pair according to the quantity changes of these
      marker compounds, which would lay foundation to further reveal the compatibility
      rule of the herb pair and other related formulae. 

PMID- 25061714
TI  - Impact of vitamin D supplementation on sustained virological response in chronic
      hepatitis C genotype 4 patients treated by pegylated interferon/ribavirin.
AB  - The current standard of care therapy (SOC) for chronic HCV is pegylated
      interferon/ribavirin (Peg-IFN/RBV). Many reports showed the possible role of
      vitamin D supplementation in augmenting the response to SOC. The aim of this
      study was to assess the role of vitamin D supplementation on the response to
      treatment in chronic HCV genotype 4 patients. One hundred and one chronic HCV
      patients were classified into two groups (Group 1): 51 patients received the SOC
      therapy consisting of Peg-interferon alfa-2b plus ribavirin, (Group 2): 50
      patients received the SOC therapy+vitamin D3 (Cholecalciferol) in a dose of
      15,000 IU/week during the treatment course. Vitamin D deficiency was found in 95%
      of patients. No correlation was found between vitamin D levels and stage of
      fibrosis in the whole population. Vitamin D supplementation had no positive
      impact on treatment outcome where sustained virological response (SVR) was
      achieved in 51.2% in group 2 and 71.4% in group 1 by per-protocol analysis and in
      44% in group 2 and in 68.6% in group 1 by intention to treat analysis (P value
      0.22 and 0.220 respectively). Despite its role in other genotypes, vitamin D
      supplementation has no significant impact on SVR in HCV Genotype 4 patient. No
      correlation was found between vitamin D levels and stage of liver fibrosis.

PMID- 25061715
TI  - Influence of evidence type and narrative type on HPV risk perception and
      intention to obtain the HPV vaccine.
AB  - This research examines the influence of evidence type (statistical, narrative, or
      hybrid) and narrative type (first-person or third-person) on risk perception
      about human papillomavirus (HPV) and behavioral intention to get the HPV vaccine.
      In total, 174 college students who had not received the HPV vaccine participated
      in a controlled experiment. Results show that the hybrid message containing both
      statistical and narrative descriptions of HPV resulted in greater perceived risk
      of getting HPV than either of the messages containing just one type of evidence-
      statistical or narrative. Moreover, the first-person narrative message led to
      greater risk perception about HPV than the third-person narrative message. Both
      evidence type and narrative type had an indirect effect on intention to get the
      HPV vaccine free of cost through HPV risk perception. Implications of the
      findings for vaccine risk communication are discussed.

PMID- 25061716
TI  - Tolerance of formulas containing prebiotics in healthy, term infants.
AB  - OBJECTIVE: The aim of the study was to compare infants' gastrointestinal
      tolerance of formulas supplemented with 2 different levels of galacto
      oligosaccharides (GOS) versus a control formula (CF) or human milk. METHODS:
      Healthy, full-term infants (n = 180) were enrolled in this 3-group controlled,
      double-blind, multicenter study, and a concurrently enrolled, nonrandomized human
      milk-fed group (HM) by 8 days of age. Infants were randomized to be fed formula
      supplemented with either 4 g (EF4) or 8 g (EF8) GOS/L or a CF until day of life
      (DOL) 119. Infants were to be seen at DOL 14, 35, 56, 84, and 119. Parents were
      to record detailed 24-hour information about intake, tolerance to feedings, and
      stool patterns and consistency each day from enrollment to DOL 35, and for 3 days
      before DOL 56, 84, and 119. Stool consistency was scored on a 5-point scale as
      watery (1), loose/mushy, soft, formed, or hard (5). RESULTS: The mean stool
      consistency score was higher in the CF group throughout the study (CF >  EF8 and
      CF > HM for all study periods and CF > EF4 from DOL 15 to 35, P < 0.05). There
      was a significantly higher percentage of watery stools in the EF8 versus the CF
      group from study day 1 (SD 1) to DOL 14 (P < 0.05), but no differences between
      the groups in number of stools per day. The percentage of feedings with spit up
      and/or vomiting within 1 hour after feeding was significantly lower for HM versus
      EF8 and CF from SD 1 to DOL 14 (P < 0.05). CONCLUSIONS: In this clinical study,
      milk-based term infant formula (Similac Advance) with 4 g GOS/L was well
      tolerated in terms of stool consistency and additional measures of
      gastrointestinal tolerance by newborn infants through the first 4 months of life.

PMID- 25061717
TI  - Antiviral effects of cyclosporine A in neonatal mice with rotavirus-induced
      diarrhea.
AB  - OBJECTIVES: Because rotavirus gastroenteritis is associated with high morbidity
      and mortality especially in developing countries, it is necessary to develop
      antirotavirus drugs for the treatment of rotavirus infection. Previous studies
      have demonstrated that cyclosporin A (CsA) has antiviral properties against
      rotavirus. Its effect has not yet been evaluated against rotavirus diarrheal
      disease. The aim of this study was to assess the anti-rotavirus efficacy of CsA
      in neonatal mice after induction of rotavirus diarrhea. METHODS: Suckling mice
      were inoculated with murine rotavirus. On the onset of diarrhea, mice were given
      different concentrations of CsA. To evaluate the effects of CsA on reduction of
      rotavirus diarrhea, diarrhea score, fecal virus shedding, and pathological lesion
      change in the small intestine, messenger RNA (mRNA) expression levels in the
      small intestine and spleen of mice were measured for type I interferon (IFN-alpha
      and IFN-beta), inflammation-related cytokines (interleukin [IL]-8, IL-10, IFN
      gamma, and tumor necrosis factor-alpha), and inflammatory signaling pathways
      (p38, c-Jun N-terminal kinase, activator protein-1, and nuclear factor-kappa B).
      RESULTS: Among virus-inoculated and CsA-treated groups, a dose of 5 mg . kg-1 .
      day-1 of CsA inhibited diarrhea and improved fecal virus shedding and intestinal
      lesion changes. IFN-beta mRNA expression was significantly increased in rotavirus
      induced diarrhea mice treated with 5 mg . kg-1 . day-1 of CsA, whereas the mRNA
      expression levels of inflammation-related cytokines (IL-8, IL-10, IFN-gamma, and
      tumor necrosis factor-alpha) and inflammatory signaling pathways (p38, c-Jun N
      terminal kinase, activator protein-1, and nuclear factor-kappa B) were markedly
      decreased. Antiviral effects of CsA were dose dependent. CONCLUSIONS: CsA can
      inhibit rotavirus infection in neonatal mice through its antiviral properties.
      The mechanism for this may be through CsA suppression of inflammation by viral
      inhibition in animal models.

PMID- 25061718
TI  - Occult Gastrointestinal Bleeding in a 15-Year-Old Pediatric Cancer Survivor.

PMID- 25061719
TI  - Coeliac disease in children with type 1 diabetes: are current guidelines proving
      difficult to implement in practice?
AB  - Updated European guidelines for the diagnosis of coeliac disease (CD) in the
      paediatric population (the European Society for Gastroenterology, Hepatology, and
      Nutrition, January 2012) outlined distinct diagnostic algorithms for patients
      with type 1 diabetes mellitus (T1DM). In this short report we demonstrate a
      period prevalence of CD in the T1DM population of 5.8% at a large tertiary
      centre. In addition to this, using a questionnaire circulated to paediatricians,
      we assessed present practice in the diagnosis of CD in T1DM 16 months following
      the European Society for Gastroenterology, Hepatology, and Nutrition guideline
      publication. Our results indicate that present practice and adherence to
      guidelines varies substantially. Further dissemination and perhaps simplification
      of guidelines may be required. 

PMID- 25061720
TI  - A QSAR, pharmacokinetic and toxicological study of new artemisinin compounds with
      anticancer activity.
AB  - The Density Functional Theory (DFT) method and the 6-31G** basis set were
      employed to calculate the molecular properties of artemisinin and 20 derivatives
      with different degrees of cytotoxicity against the human hepatocellular carcinoma
      HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis
      (HCA) were employed to select the most important descriptors related to
      anticancer activity. The significant molecular descriptors related to the
      compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP
      energy. The Pearson correlation between activity and most important descriptors
      were used for the regression partial least squares (PLS) and principal component
      regression (PCR) models built. The regression PLS and PCR were very close, with
      variation between PLS and PCR of R(2) = +/- 0.0106, R(2)(ajust) = +/- 0.0125, s =
      +/- 0.0234, F(4,11) = +/- 12.7802, Q(2) = +/- 0.0088, SEV = +/- 0.0132, PRESS =
      +/- 0.4808 and SPRESS = +/- 0.0057. These models were used to predict the
      anticancer activity of eight new artemisinin compounds (test set) with unknown
      activity, and for these new compounds were predicted pharmacokinetic properties:
      human intestinal absorption (HIA), cellular permeability (PCaCO2), cell
      permeability Maden Darby Canine Kidney (PMDCK), skin permeability (P(Skin)),
      plasma protein binding (PPB) and penetration of the blood-brain barrier
      (C(Brain/Blood)), and toxicological: mutagenicity and carcinogenicity. The test
      set showed for two new artemisinin compounds satisfactory results for anticancer
      activity and pharmacokinetic and toxicological properties. Consequently, further
      studies need be done to evaluate the different proposals as well as their
      actions, toxicity, and potential use for treatment of cancers.

PMID- 25061721
TI  - Synthesis and biological activities of some new (Nalpha-dinicotinoyl)-bis-L
      leucyl linear and macrocyclic peptides.
AB  - A series of linear and macrocyclic peptides 3-12 were synthesized using 3,5
      pyridinedicarboxylic acid (1) as starting material and screened for their
      antimicrobial, anti-inflammatory and anticancer activities. Bis-ester 3 was
      prepared from 1 and L-leucine methyl ester. Hydrazinolysis and hydrolysis of
      dipeptide methyl ester 3 with hydrazine hydrate or 1 N sodium hydroxide afforded
      compounds 4 and 5, respectively. Cyclization of the dipeptide 5 with L-lysine
      methyl ester afforded cyclic pentapeptide ester 6. Compounds 7-9 were synthesized
      by reacting hydrazide 4 with phthalic anhydride, 1,8-naphthalene anhydride or
      acetophenone derivatives. Treatment of acid hydrazide 4 with aromatic aldehydes
      or tetraacid dianhydrides afforded the corresponding bis-dipeptide hydrazones 10a
      e and macrocyclic peptides 11 and 12, respectively. The structures of newly
      synthesized compounds were confirmed by IR, 1H-NMR, MS spectral data and
      elemental analysis. The detailed synthesis, spectroscopic data, biological and
      pharmacological activities of the synthesized compounds was reported. 

PMID- 25061722
TI  - Transcriptional responses of the Bdtf1-deletion mutant to the phytoalexin
      brassinin in the necrotrophic fungus Alternaria brassicicola.
AB  - Brassica species produce the antifungal indolyl compounds brassinin and its
      derivatives, during microbial infection. The fungal pathogen Alternaria
      brassicicola detoxifies brassinin and possibly its derivatives. This ability is
      an important property for the successful infection of brassicaceous plants.
      Previously, we identified a transcription factor, Bdtf1, essential for the
      detoxification of brassinin and full virulence. To discover genes that encode
      putative brassinin-digesting enzymes, we compared gene expression profiles
      between a mutant strain of the transcription factor and wild-type A. brassicicola
      under two different experimental conditions. A total of 170 and 388 genes were
      expressed at higher levels in the mutants than the wild type during the infection
      of host plants and saprophytic growth in the presence of brassinin, respectively.
      In contrast, 93 and 560 genes were expressed, respectively, at lower levels in
      the mutant than the wild type under the two conditions. Fifteen of these genes
      were expressed at lower levels in the mutant than in the wild type under both
      conditions. These genes were assumed to be important for the detoxification of
      brassinin and included Bdtf1 and 10 putative enzymes. This list of genes provides
      a resource for the discovery of enzyme-coding genes important in the chemical
      modification of brassinin. 

PMID- 25061723
TI  - Hypericum japonicum Thunb. ex Murray: phytochemistry, pharmacology, quality
      control and pharmacokinetics of an important herbal medicine.
AB  - Hypericum japonicum Thunb. ex Murray is mainly distributed throughout Asia,
      Oceania and North America and is used as an important herbal medicine. H.
      japonicum contains many valuable secondary metabolites, such as flavonoids,
      phloroglucinols and xanthones and has hepatoprotective, anti-tumor,
      antibacterial, antiviral, and antioxidant activities and effects on the
      cardiovascular system and immunity. Coupled with phytochemical and
      pharmacological research, a series of analytical methods have been developed to
      evaluate the quality of H. japonicum based on its bioactive components. A
      pharmacokinetics study involved the absorption of two main flavonoids of H.
      japonicum in rats. This review aims to present an up-to-date and comprehensive
      overview of the phytochemistry, pharmacology, quality control and
      pharmacokinetics of H. japonicum, which should be useful for the greater
      development of H. japonicum, especially in the development of new drugs and
      therapeutics for various diseases. 

PMID- 25061724
TI  - Metal complexes containing natural and and artificial radioactive elements and
      their applications.
AB  - Recent advances (during the 2007-2014 period) in the coordination and
      organometallic chemistry of compounds containing natural and artificially
      prepared radionuclides (actinides and technetium), are reviewed. Radioactive
      isotopes of naturally stable elements are not included for discussion in this
      work. Actinide and technetium complexes with O-, N-, N,O, N,S-, P-containing
      ligands, as well pi-organometallics are discussed from the view point of their
      synthesis, properties, and main applications. On the basis of their properties,
      several mono-, bi-, tri-, tetra- or polydentate ligands have been designed for
      specific recognition of some particular radionuclides, and can be used in the
      processes of nuclear waste remediation, i.e., recycling of nuclear fuel and the
      separation of actinides and fission products from waste solutions or for
      analytical determination of actinides in solutions; actinide metal complexes are
      also usefulas catalysts forcoupling gaseous carbon monoxide,as well as
      antimicrobial and anti-fungi agents due to their biological activity. Radioactive
      labeling based on the short-lived metastable nuclide technetium-99m ((99m)Tc) for
      biomedical use as heart, lung, kidney, bone, brain, liver or cancer imaging
      agents is also discussed. Finally, the promising applications of technetium
      labeling of nanomaterials, with potential applications as drug transport and
      delivery vehicles, radiotherapeutic agents or radiotracers for monitoring
      metabolic pathways, are also described.

PMID- 25061725
TI  - Effects of single amino acid substitution on the biophysical properties and
      biological activities of an amphipathic alpha-helical antibacterial peptide
      against Gram-negative bacteria.
AB  - An antimicrobial peptide, known as V13K, was utilized as the framework to study
      the effects of charge, hydrophobicity and helicity on the biophysical properties
      and biological activities of alpha-helical peptides. Six amino acids (Lys, Glu,
      Gly, Ser, Ala, and Leu) were individually used to substitute the original
      hydrophobic valine at the selected sixteenth location on the non-polar face of
      V13K. The results showed that the single amino acid substitutions changed the
      hydrophobicity of peptide analogs as monitored by RP-HPLC, but did not cause
      significant changes on peptide secondary structures both in a benign buffer and
      in a hydrophobic environment. The biological activities of the analogs exhibited
      a hydrophobicity-dependent behavior. The mechanism of peptide interaction with
      the outer membrane and cytoplasmic membrane of Gram-negative bacteria was
      investigated. We demonstrated that this single amino acid substitution method has
      valuable potential for the rational design of antimicrobial peptides with
      enhanced activities. 

PMID- 25061726
TI  - Cudarflavone B provides neuroprotection against glutamate-induced mouse
      hippocampal HT22 cell damage through the Nrf2 and PI3K/Akt signaling pathways.
AB  - Oxidative cell damage contributes to neuronal degeneration in many central
      nervous system (CNS) diseases such as Alzheimer's disease, Parkinson's disease,
      and ischemia. Nrf2 signaling-mediated heme oxygenase (HO)-1 expression acts
      against oxidants that are thought to play a key role in the pathogenesis of
      neuronal diseases. Cudraflavone B is a prenylated flavone isolated from C.
      tricuspidata which has shown anti-proliferative activity, mouse brain monoamine
      oxidase (MAO) inhibitory effects, apoptotic actions in human gastric carcinoma
      cells and mouse melanoma cells, and hepatoprotective activity. In this study,
      cudraflavone B showed neuroprotective effects and reactive oxygen species (ROS)
      inhibition against glutamate-induced neurotoxicity by inducing the expression of
      HO-1 in mouse hippocampal HT22 cells. Furthermore, cudraflavone B caused the
      nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased
      the promoter activity of antioxidant response elements (ARE) in mouse hippocampal
      HT22 cells. In addition, we found that the Nrf2-midiated HO-1 expression by
      cudraflavone B is involved in the cell protective response and ROS reductions,
      and cudraflavone B-induced expression of HO-1 was mediated through the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway in HT22 cells. Our results
      demonstrated the potential application of naturally occurring cudraflavone B as a
      therapeutic agent from neurodegenerative disease. 

PMID- 25061727
TI  - Purification and characterization of guanylate kinase, a nucleoside monophosphate
      kinase of Brugia malayi.
AB  - Guanylate kinase, a nucleoside monophosphate kinase of Brugia malayi which is
      involved in reversible transfer of phosphate groups from ATP to GMP, was cloned,
      expressed and characterized. The native molecular mass of BmGK was found to be 45
      kDa as determined by size exclusion chromatography and glutaraldehyde cross
      linking which revealed that the protein is homodimer in nature. This is a unique
      characteristic among known eukaryotic GKs. GMP and ATP served as the most
      effective phosphate acceptor and donor, respectively. Recombinant BmGK utilized
      both GMP and dGMP, as substrates showing Km values of 30 and 38 MU m,
      respectively. Free Mg+2 (un-complexed to ATP) and GTP play a regulatory role in
      catalysis of BmGK. The enzyme showed higher catalytic efficiency as compared with
      human GK and showed ternary complex (BmGK-GMP-ATP) formation with sequential
      substrate binding. The secondary structure of BmGK consisted of 45% alpha
      helices, 18% beta-sheets as revealed by CD analysis. Homology modelling and
      docking with GMP revealed conserved substrate binding residues with slight
      differences. Differences in kinetic properties and oligomerization of BmGK
      compared with human GK can provide the way for design of parasite-specific
      inhibitors.

PMID- 25061728
TI  - Integrated transcriptional and metabolic profiling in human endotoxemia.
AB  - In this meta-study, we aimed to integrate biological insights gained from two
      levels of -omics analyses on the response to systemic inflammation induced by
      lipopolysaccharide in humans. We characterized the interplay between plasma
      metabolite compositions and transcriptional response of leukocytes through
      integration of transcriptomics with plasma metabonomics. We hypothesized that the
      drastic changes in the immediate environment of the leukocytes might have an
      adaptive effect on shaping their transcriptional response in conjunction with the
      initial inflammatory stimuli. Indeed, we observed that leukocytes, most notably,
      tune the activity of lipid- and protein-associated processes at the
      transcriptional level in accordance with the fluctuations in metabolite
      compositions of surrounding plasma. A closer look into the transcriptional
      control of only metabolic pathways uncovered alterations in bioenergetics and
      defenses against oxidative stress closely associated with mitochondrial
      dysfunction and shifts in energy production observed during inflammatory
      processes. 

PMID- 25061729
TI  - Association of miR-149C>T and miR-499A>G polymorphisms with the risk of
      hepatocellular carcinoma in the Chinese population.
AB  - We investigate the potential association of miR-149C>T and miR-499A>G
      polymorphisms and the risk of hepatocellular carcinoma (HCC). A matched case
      control study of 152 cases and 304 controls were conducted. The miR-149C>T and
      miR-499A>G genotypes were analyzed using duplex polymerase chain reaction with
      restricted fragment length polymorphism. HCC patients were more likely to be
      smokers and drinkers, have hepatitis B and C virus infections, and a family
      history of cancer. The miR-149 CC genotype was associated with a reduced risk of
      HCC, while the miR-499 GG genotype was associated with an increased risk of HCC.
      However, we did not find that the miR-149 CC and miR-499 GG genotypes were
      associated with risk of HCC, and no interaction was found between miR-149C>T and
      miR-499A>G polymorphisms and hepatitis B virus infection. In conclusion, the
      miRNA-149C>T and miR-499A>G polymorphisms were found to play an important role
      for HCC risk in China. This finding could be useful in identifying people at high
      risk for the disease for early intervention. 

PMID- 25061730
TI  - Equol promotes rat osteoblast proliferation and differentiation through
      activating estrogen receptor.
AB  - Phytoestrogens have been suggested as alternative treatment for postmenopausal
      osteoporosis. Equol, a metabolite of daidzein, has been shown to inhibit bone
      loss in ovariectomized mice and rats. However, whether or not equol influences
      the formation of bone has not yet been investigated. Therefore, we investigated
      the effect of equol on the proliferation and differentiation of rat primary
      osteoblasts and explored the involved mechanisms. Different equol concentrations
      significantly promoted the proliferation of osteoblasts after 48- and 72-h
      incubations. The alkaline phosphatase (ALP) activity also increased significantly
      in all of the equol and 17beta-estradiol (E2) groups, except for the lowest (0.01
      MUM) equol group. Equol also significantly elevated the osteocalcin levels. The
      effects of equol on osteoblast proliferation, ALP activity, and osteocalcin
      levels were blocked by the estrogen receptor (ER) antagonist ICI182780. After a
      24-h incubation, the expression of protein kinase C alpha (PKCalpha) in
      osteoblasts was significantly increased by equol. In conclusion, our study
      demonstrated that equol could promote the proliferation and differentiation of
      rat osteoblasts through activating the ER-PKCalpha-related signaling pathway,
      suggesting that equol could promote bone formation. These results suggest that
      equol could be a potential alternative agent for the management of postmenopausal
      osteoporosis. 

PMID- 25061731
TI  - 5-Azacytidine suppresses the proliferation of pancreatic cancer cells by
      inhibiting the Wnt/beta-catenin signaling pathway.
AB  - 5-Azacytidine has been shown to be an effective anti-pancreatic cancer drug, but
      the mechanism remains unknown. In the current study, we explored the effect of 5
      azacytidine on abnormal activation of the Wnt-beta-catenin signaling pathway in
      pancreatic cancer cells. The human pancreatic cancer cell line Bxpc-3 was treated
      with different concentrations of 5-azacytidine for various times. The
      proliferation and early apoptosis of the cells were evaluated using the CCK8
      method and flow cytometry, respectively. mRNA and protein expression of beta
      catenin, c-myc, and cyclinD1 were detected using real-time fluorescent
      quantitative polymerase chain reaction and Western blot analysis, respectively.
      The proliferation of Bxpc-3 cells was suppressed by 5-azacytidine. The early
      apoptosis of the cells was significantly enhanced over time and with increasing
      drug concentrations. The expression of beta-catenin, c-myc, and cyclinD1 were
      down-regulated, showing significant differences between different concentrations
      and treatment times (P < 0.05). 5-Azacytidine suppressed the proliferation of
      pancreatic cancer cells by inhibiting the Wnt/beta-catenin signaling pathway,
      particularly the expression of beta-catenin, c-myc, and cyclinD1. This study may
      provide a new potential strategy for diagnosing and treating pancreatic cancer. 

PMID- 25061732
TI  - Identifying human disease genes: advances in molecular genetics and computational
      approaches.
AB  - The human genome project is one of the significant achievements that have
      provided detailed insight into our genetic legacy. During the last two decades,
      biomedical investigations have gathered a considerable body of evidence by
      detecting more than 2000 disease genes. Despite the imperative advances in the
      genetic understanding of various diseases, the pathogenesis of many others
      remains obscure. With recent advances, the laborious methodologies used to
      identify DNA variations are replaced by direct sequencing of genomic DNA to
      detect genetic changes. The ability to perform such studies depends equally on
      the development of high-throughput and economical genotyping methods. Currently,
      basically for every disease whose origen is still unknown, genetic approaches are
      available which could be pedigree-dependent or -independent with the capacity to
      elucidate fundamental disease mechanisms. Computer algorithms and programs for
      linkage analysis have formed the foundation for many disease gene detection
      projects, similarly databases of clinical findings have been widely used to
      support diagnostic decisions in dysmorphology and general human disease. For
      every disease type, genome sequence variations, particularly single nucleotide
      polymorphisms are mapped by comparing the genetic makeup of case and control
      groups. Methods that predict the effects of polymorphisms on protein stability
      are useful for the identification of possible disease associations, whereas
      structural effects can be assessed using methods to predict stability changes in
      proteins using sequence and/or structural information. 

PMID- 25061733
TI  - Association of peroxisome proliferator-activated receptor-delta polymorphisms
      with sugar metabolism indices and tumor necrosis factor alpha level.
AB  - This study aims to investigate the association of peroxisome proliferator
      activated receptor (PPAR) delta -87T/C polymorphism with several sugar metabolism
      indices and tumor necrosis factor alpha (TNF alpha) level. The body mass index
      (BMI), waist size, and levels of fasting plasma glucose, serum lipid, fasting
      insulin, TNFalpha, and PPAR delta -87T/C of 286 patients with type 2 diabetes
      mellitus (T2DM) and 158 subjects with normal fasting glucose (NFG) were measured
      in a Dalian population. The distribution of genotypic frequencies between T2DM
      and NFG were not significantly different (chi(2) = 0.012, P = 0.994). BMI,
      fasting blood glucose (FBG), homeostasis model assessment-estimated insulin
      resistance (HOMA-IR), triglyceride, and TNFalpha levels were significantly
      different among different T2DM genotypes. HOMA-IR and FBG were significantly
      different among different NFG genotypes. The PPAR delta -87T/C polymorphism is
      known to be closely related with glucose levels and lipid metabolism. A close
      relationship was also found between HOMA-IR and TNFalpha levels and HOMA-IR and
      FBG in T2DM and NFG, respectively. 

PMID- 25061734
TI  - Effects of VEGF suppression by small hairpin RNA interference combined with
      radiotherapy on the growth of cervical cancer.
AB  - This study aimed to investigate the inhibition of vascular endothelial growth
      factor (VEGF) by small hairpin RNA (shRNA) interference combined with
      radiotherapy on the growth of cervical cancer SiHa cell xenografts in nude mice.
      The effective pVEGF-shRNA plasmid was screened by reverse transcription
      polymerase chain reaction (RT-PCR), and the cell apoptosis rate was estimated by
      flow cytometry. A nude mouse cervical xenograft model was established and all
      models were divided into four groups: blank control, VEGF shRNA, radiotherapy,
      and combined treatment. We calculated the tumor growth curve and the inhibitory
      rate. The histopathological changes of the microvascular density and VEGF protein
      expression were observed by immunohistochemistry. The expressions of VEGF and
      hypoxia inducible factor-1alpha (HIF-1alpha) proteins in the tumor tissue were
      analyzed via Western blot. VEGF shRNA interference inhibited the expression of
      radiation-induced VEGF (P < 0.05), induced apoptosis (P < 0.05), downregulated
      the HIF-1alpha protein, and reduced angiogenesis. Compared with the other three
      groups, the combined treatment group showed the most significant effects (P <
      0.01). VEGF shRNA interference combined with radiotherapy promotes the
      radiosensitivity of tumors via improvement of the hypoxic microenvironment. 

PMID- 25061735
TI  - Analysis of thyroid peroxidase antibody in early pregnancy.
AB  - This study aimed to investigate the thyroid peroxidase antibody (TPOAb) positive
      rate and how TPOAb affects thyroid function between 7 and 12 weeks of gestation.
      Six hundred and eleven cases of healthy primipara were enrolled in this study
      between September 2010 and June 2011, and all of them were given a regular
      prenatal check in Beijing Friendship Hospital. By detecting the levels of thyroid
      stimulating hormone (TSH), free thyroxine (FT4), and TPOAb between 7 to 12 weeks
      gestation, we developed an early thyroid function normal reference interval
      during pregnancy. Additionally, we analyzed the TPOAb-positivity cutoff value,
      the positive rate, and the affect of TSH and FT4. We found that the TPOAb median
      values and changes in the range were 38.9 (6.4-1300+) mU/L. By establishing an 7
      12 week gestational-specific reference standard for pregnancy, we set a positive
      cutoff value of 206.77 mU/L according to the 90th percentile TPOAb. The TPOAb
      positive rate was 10.8% (66/611). Regression analysis showed that, during
      gestation between 7 and 12 weeks, the titers of TPOAb and TSH correlate
      positively and negatively with FT4, beta = 1.406 and 0.820, respectively [95%CI
      (1.349-1.413, 0.805-0.835), P = 0.000]. Pregnant TPOAb positive women are more
      likely to suffer from markedly increased TSH levels, with increased risk being 3
      4-fold greater than in a normal pregnancy. 

PMID- 25061736
TI  - Wnt/beta-catenin aids in regulating the proliferation of hepG2 cells mediated by
      thy-1.
AB  - Cancer stem cells have been found to play important roles in carcinoma. Although
      thy-1 has been identified as a potential stem cell marker of liver cancer,
      whether the Wnt/beta-catenin signaling pathway plays an important role in
      regulating hepatocarcinoma proliferation and apoptosis mediated by thy-1 remains
      unknown. Our results showed that high thy-1 expression caused hepG2 cells
      transfected with a pReceiver-M29/thy-1 eukaryotic expression vector to exhibit
      obvious heteromorphism, featuring double or multiple nuclei and weaker apoptosis.
      A high expression of beta-catenin, as a critical signaling protein of Wnt/beta
      catenin, and its downstream transcription factor, cyclinD1, were detected in
      transfected hepG2 cells. We also used aspirin as an inhibitor of the Wnt
      signaling pathway in the treatment of hepG2 cells transfected with the pReceiver
      M29/thy-1 expression vector to make detailed observations of apoptosis in hepG2
      cells as well as the differential expression of beta-catenin, cyclinD1, and thy
      1. An increasing apoptosis rate was detected in the hepG2 cells and downregulated
      expression of the three proteins was detected. Hence, we suggest that thy-1
      upregulation promotes the proliferation and inhibits apoptosis of hepG2 cells,
      and that these processes are regulated by the Wnt/beta- catenin signaling
      pathway. 

PMID- 25061737
TI  - Clinical effects and safety review of self-expanding stent surgery for
      extracranial carotid artery stenosis treatment.
AB  - This study aimed to investigate the clinical effects and safety review of self
      expanding stent surgery in the treatment of extracranial carotid artery stenosis.
      Seventy-eight patients with carotid artery stenosis were applied with the self
      expanding stent for endovascular interventional therapy. Eighty-one stents were
      implanted into 80 blood vessels of the 78 patients, in which protective umbrellas
      were used in 56 cases, and the success rate of stent implantation was 100%. The
      stenosis degree decreased from the preoperative (86.72 +/- 9.5%) to the
      postoperative (13.43 +/- 5.62%) stage, and the blood peak velocity of the
      stenosed vessels decreased from 189.58 +/- 13.5 to 83.73 +/- 5.61 cm/s. Transient
      blood pressure and heart rate decreases occurred in 21 cases, continuously low
      blood pressure and heart rate decreasing occurred in 29 cases, and acute
      occlusion of the ipsilateral middle cerebral artery occurred in 1 case, which was
      resolved through thrombolysis and thrombus breaking in time. Over-perfusion
      symptoms were observed in 13 cases, although without serious complications such
      as cerebral hemorrhage. The follow-up period continued for 6-32 months, and
      ultrasonography revealed that 77 cases had no stent-restenosis, while 1 case had
      restenosis. The application of self-expanding stents had good clinical effects,
      with fewer complications and higher safety for the treatment of extracranial
      carotid artery stenosis. 

PMID- 25061738
TI  - Development and characterization of microsatellite loci for Ocotea species
      (Lauraceae) threatened with extinction.
AB  - The Atlantic rainforest species Ocotea catharinensis, Ocotea odorifera, and
      Ocotea porosa have been extensively harvested in the past for timber and oil
      extraction and are currently listed as threatened due to overexploitation. To
      investigate the genetic diversity and population structure of these species, we
      developed 8 polymorphic microsatellite markers for O. odorifera from an enriched
      microsatellite library by using 2 dinucleotide repeats. The microsatellite
      markers were tested for cross-amplification in O. catharinensis and O. porosa.
      The average number of alleles per locus was 10.2, considering all loci over 2
      populations of O. odorifera. Observed and expected heterozygosities for O.
      odorifera ranged from 0.39 to 0.93 and 0.41 to 0.92 across populations,
      respectively. Cross-amplification of all loci was successfully observed in O.
      catharinensis and O. porosa except 1 locus that was found to lack polymorphism in
      O. porosa. Combined probabilities of identity in the studied Ocotea species were
      very low ranging from 1.0 x 10-24 to 7.7 x 10-24. The probability of exclusion
      over all loci estimated for O. odorifera indicated a 99.9% chance of correctly
      excluding a random nonparent individual. The microsatellite markers described in
      this study have high information content and will be useful for further
      investigations on genetic diversity within these species and for subsequent
      conservation purposes. 

PMID- 25061739
TI  - Serum levels of high-sensitivity troponin T: a novel marker for left ventricular
      remodeling and performance in hypertensive subjects.
AB  - It has been well established that high-sensitivity cardiac troponin T (hs-TnT) is
      a specific and highly sensitive marker in acute coronary syndromes. On the other
      hand, studies on serum concentrations of hs-TnT in patients with hypertension in
      the absence of significant coronary stenosis are limited. Therefore, we
      hypothesized that hs-TnT levels are related to left ventricular (LV) remodeling
      and performance in hypertension. We included 537 hemodynamically stable
      hypertensive subjects, 247 males aged 60.7 +/- 11.1 years, and 100 normotensive
      subjects of similar age and gender. Clinical examination, clinical assessment and
      laboratory assays were performed for all hypertensive and normotensive subjects.
      The detectable rate (>0.003 ng/mL) and elevated rate (>0.013 ng/mL) of hs-TnT
      were higher in hypertensive subjects than those in normotensive subjects. hs-TnT
      level gradually increased in hypertensive subjects with LV normal geometry,
      concentric remodeling, concentric hypertrophy and eccentric hypertrophy. hs-TnT
      was independently related to age, gender, hypertension, fasting blood glucose,
      renal function, and LV hypertrophy, and diastolic function on multiple analysis
      during the whole participation. An increase in hs-TnT levels could be a reliable
      biomarker of cardiac remodeling and function in hypertension, as an indicator of
      subclinical ongoing cardiomyocyte injury. 

PMID- 25061740
TI  - Nucleolar activity during larval development of Myrmeleon uniformis Navas, 1920
      (Neuroptera, Myrmeleontidae).
AB  - It has been reported in the literature that the Malpighian tubules of Neuroptera
      in the third instar undergo drastic histological changes, when they stop
      functioning in osmoregulation and start to secrete silk fibers for a cocoon.
      Therefore, to increase our knowledge about these cellular alterations that occur
      in the larvae of Neuroptera, we analyzed the cells that constitute the Malpighian
      tubules of each larval instar of the species Myrmeleon uniformis, with emphasis
      on nucleolar activity. Malpighian tubules, after being removed, were fixed on a
      slide using liquid nitrogen and stained by silver impregnation. In addition,
      total protein of the tubules was quantified. By analyzing the cells in the first
      instar larval stage, we observed only two silver-stained nucleolar regions. In
      cells of second instar larvae, there was an increase in the number of stained
      regions, and in the third instar, the number of nucleolar regions was very large.
      Agarose gel electrophoresis indicated that third instar larvae had high synthetic
      activity, where the total amount of proteins was larger in third instar stage
      than in the other larval stages. Furthermore, the most abundant proteins
      displayed molecular weights of about 32-43 kDa and were probably precursors of
      silk fibers. Thus, the results obtained showed that nucleolar alterations occur
      in the cells of the Malpighian tubules of larval instars of M. uniformis and this
      is directly related to the production of silk fibers used by the pupa to ensure
      the completion of metamorphosis. 

PMID- 25061741
TI  - Comprehensive gene expression analysis of the DNA (cytosine-5) methyltransferase
      family in rice (Oryza sativa L.).
AB  - Cytosine DNA methylation is a conserved epigenetic regulatory mechanism in both
      plants and animals. DNA methyltransferases (DNA MTases) not only initiate (de
      novo) but also maintain the process of DNA methylation. Here, we characterized
      the genome-wide expression profiles of 10 cytosine DNA MTase genes belonging to 4
      subfamilies, MET1, CMT, DNMT2, and DRM, in rice. Tissue-specific gene expression
      analysis showed that all family members varied widely in their expression and
      specificities and might be involved in some basic metabolic pathways. Similarly,
      the expression of all rice cytosine DNA MTase genes was not regulated by plant
      hormones except OsDRM1a and OsDRM1b, which were downregulated by jasmonic acid.
      The transcription level of 10 genes in rice shoots and roots was also measured
      under salt and osmotic stress. Meanwhile, quantitative polymerase chain reaction
      data of the japonica and indica rice cultivars revealed that there is large
      variation in the expression activities of all genes. The results provide a
      foundation to further explore the roles of DNA MTases and the epigenetic
      regulation of abiotic stress responses in rice. 

PMID- 25061742
TI  - Role of aluminum adjuvant in producing an allergic rhinitis animal model.
AB  - This study evaluated different dosage forms of aluminum adjuvant in generating
      allergic rhinitis animal models. Forty female BALB/c mice were assigned to four
      groups, including three dosage forms of aluminum adjuvant [powder, gel, and
      hydrosolvent of aluminum hydroxide, Al(OH)3] mixed with ovalbumin to simulate the
      symptoms of allergic rhinitis and one control group. Although the aluminum
      adjuvants were in different dosage forms, the content was 5 mg after conversion
      in all groups. The fourth group was given normal saline instead as a control.
      Mice of the powder group displayed typical symptoms of allergic rhinitis. We also
      found discrete eosinophils in the nasal mucosa of mice from the hydrosolvent
      group; however, no eosinophils were found in the gel group. These two groups both
      displayed cytotoxic symptoms and foreign body granuloma. Aluminum adjuvant used
      in producing animal models can induce foreign body granuloma and other untoward
      reactions, which are associated with the dosage level and form. 

PMID- 25061743
TI  - Relationship between RUNX3 methylation and hepatocellular carcinoma in Asian
      populations: a systematic review.
AB  - Runt-related transcription factor 3 (RUNX3) is a potential tumor suppressor that
      is frequently hypermethylated in hepatocellular carcinoma (HCC). The present meta
      analysis of case-control studies was carried out to determine whether RUNX3
      hypermethylation is associated with HCC. The PubMed, Embase, and Chinese National
      Knowledge Infrastructure databases were searched for all relevant studies
      published between May 2000 and May 2012. A total of 11 studies were identified,
      and 8 studies involving 491 patients with HCC and 409 patients without tumors
      were found to satisfy the inclusion criteria for the meta-analysis. All tissue
      samples were from Asian populations. There was significant heterogeneity between
      the studies. Over the entire sample, the odds ratio (OR) of RUNX3 promoter
      methylation was 18.5 [95% confidence interval (CI), 11.6-29.6] for HCC tissues
      relative to control tissues. The ORs of RUNX3 methylation were 16.6 (95%CI = 6.5
      42.4) for tumor tissues relative to tumor-adjacent tissues in patients with HCC,
      67.3 (95%CI = 13.0-348.5) for tumor tissues from patients with HCC relative to
      liver tissues from patients with non-neoplastic liver diseases, and 3.26 (95%CI =
      1.54-6.90) for tissues from patients with hepatitis C virus (HCV)- related HCC
      relative to liver tissues from patients with HCC unrelated to HCV. There was no
      association between RUNX3 methylation and age, gender, pathological stage, or
      hepatitis B virus infection in HCC tissues. Methylation of the RUNX3 promoter
      strongly correlated with HCC in Asian populations, especially in individuals with
      HCV-related HCC, and may be a useful marker for HCC diagnosis in these
      populations. 

PMID- 25061744
TI  - Tumor necrosis factor receptor-II nt587 polymorphism in Chinese Han patients with
      ankylosing spondylitis.
AB  - We aimed to explore the association between the onset of ankylosing spondylitis
      (AS) and nt587 polymorphisms of the tumor necrosis factor receptor II (TNFRII)
      gene in the Han population of Hunan Province, China. Correlation analysis was
      performed in a case-control study involving 100 AS cases and 100 healthy
      controls. The nt587 single nucleotide polymorphism of the TNFRII gene was
      examined by polymerase chain reaction-restriction fragment length polymorphism.
      The relationship between AS and the frequencies of genotypes and alleles in
      TNFRII nt587 were analyzed using the SPSS software. There were 43 cases with the
      TNFRII nt587 T/T genotype, 32 cases with the TNFRII nt587 T/G genotype, and 25
      cases with the TNFRII nt587 G/G genotype. In the 100 healthy controls, 56
      subjects had the TNFRII nt587 T/T genotype, 34 had the TNFRII nt587 T/G genotype,
      and 10 had the TNFRII nt587 G/G genotype. The G allele frequency of the AS group
      was significantly higher (chi(2) = 8.734, P = 0.003) than that in the control
      group (41.0 vs 27.0%). The odds ratio (OR) in AS cases with the TNFRII nt587 G/G
      genotype was 3.256, which was obviously higher than in those with T/G (OR =
      1.226) and T/T (OR = 1.0) genotype. The polymorphism at position nt587 of the
      TNFRII gene was found to be associated with AS, and the TNFRII nt587 G allele may
      play an important role in AS susceptibility. The TNFRII nt587 G/G genotype may
      increase the risk of developing AS in the Hunan population. 

PMID- 25061745
TI  - Comparative analysis of mucosal immunity to Mycoplasma hyopneumoniae in
      Jiangquhai porcine lean strain and DLY piglets.
AB  - The Jiangquhai porcine lean strain (JQHPL) is a new pork meat-type strain that
      has been developed in recent years from the parent lines Duroc, Fengjing, and
      Jiangquhai pigs (DurocxFengjing pigxJiangquhai pig). Enzootic pneumonia (EP) in
      pigs induced by Mycoplasma hyopneumoniae (M. hyopneumoniae) is a chronic
      respiratory disease of pigs, generating high economic losses in the swine
      industry. Here, we investigated the degree of resistance to M. hyopneumoniae for
      the Jiangquhai porcine lean strain and the Duroc x Landrace x Yorkshire (DLY)
      pigs, which are Western commercial pigs that have been introduced in China. A
      total of 209 DLY piglets and 221 JQHPL piglets from 19 Landrace x Yorkshire and
      22 JQHPL M. hyopneumoniae positive gestating sows with different expected dates
      of confinement were selected and raised in the same M. hyopneumoniae positive
      farrowing barn. When the oldest suckling piglets were 37 days old, nasal swabs
      were collected from all the piglets (ranging from 4 to 37 days old) to detect the
      M. hyopneumoniae pathogen using n-PCR and M. hyopneumoniae specific SIgA using
      ELISA. Positive M. hyopneumoniae infection rates in both the strains increased
      with age; however, positive rates for JQHPL were lower compared to DLY at 14 to
      35 days old. The level of the specific SIgA rose rapidly in JQHPL respiratory
      tracts, particularly in piglets 21 to 35 days in age compared to DLY piglets of
      the same age; however, the level of the specific SIgA in DLY also marginally
      increased. In conclusion, JQHPL pigs exhibits higher resistance to M.
      hyopneumoniae compared to DLY. It is possible that this characteristic is caused
      by the faster and stronger mucosal immunity phenotype of the JQHPL strain. 

PMID- 25061746
TI  - Mutagenic potential of Cordia ecalyculata alone and in association with Spirulina
      maxima for their evaluation as candidate anti-obesity drugs.
AB  - Obesity is one of the most important nutritional disorders, and can be currently
      considered as an epidemic. Although there are few weight reduction drugs
      available on the market, some new drug candidates have been proposed, including
      Cordia ecalyculata, a Brazilian plant with anorectic properties, and Spirulina
      maxima, a cyanobacterium with antioxidant and anti-genotoxic activity. In this
      study, we evaluated the mutagenic potential of C. ecalyculata at doses of 150,
      300, and 500 mg/kg alone and in association with S. maxima at doses of 75, 150,
      and 250 mg/kg, respectively, through an in vivo micronucleus test, using mice of
      both sexes, and an in vitro micronucleus test and comet assay, using human
      peripheral blood. For all tests, cyclophosphamide was used as a positive control.
      The results showed that treatment of 300 mg/kg C. ecalyculata and the combination
      treatment of 500 mg/kg C. ecalyculata with 250 mg/kg S. maxima resulted in
      anorectic effects. The mutagenic tests did not reveal any clastogenic or
      genotoxic activity for any treatment, indicating that these candidates could be
      marketed as weight-reduction drugs. Moreover, the drugs contain chemo-preventive
      substances that can protect against tumorigenesis, which has been associated with
      obesity. 

PMID- 25061747
TI  - Genetically modified crops: Brazilian law and overview.
AB  - In Brazil, the first genetically modified (GM) crop was released in 1998, and it
      is estimated that 84, 78, and 50% of crop areas containing soybean, corn, and
      cotton, respectively, were transgenic in 2012. This intense and rapid adoption
      rate confirms that the choice to use technology has been the main factor in
      developing national agriculture. Thus, this review focuses on understanding these
      dynamics in the context of farmers, trade relations, and legislation. To
      accomplish this goal, a survey was conducted using the database of the National
      Cultivar Registry and the National Service for Plant Variety Protection of the
      Ministry of Agriculture, Livestock and Supply [Ministerio da Agricultura,
      Pecuaria e Abastecimento (MAPA)] between 1998 and October 13, 2013. To date, 36
      events have been released: five for soybeans, 18 for corn, 12 for cotton, and one
      for beans. From these events, 1395 cultivars have been developed and registered:
      582 for soybean, 783 for corn and 30 for cotton. Monsanto owns 73.05% of the
      technologies used to develop these cultivars, while the Dow AgroScience - DuPont
      partnership and Syngenta have 16.34 and 4.37% ownership, respectively. Thus, the
      provision of transgenic seeds by these companies is an oligopoly supported by
      legislation. Moreover, there has been a rapid replacement of conventional crops
      by GM crops, whose technologies belong almost exclusively to four multinational
      companies, with the major ownership by Monsanto. These results reflect a warning
      to the government of the increased dependence on multinational corporations for
      key agricultural commodities. 

PMID- 25061749
TI  - Cation-pi interactions in protonated phenylalkylamines.
AB  - Phenylalkylamines of the general formula C6H5(CH2)nNH2 (n = 1-4) have been
      delivered to the gas phase as protonated species using electrospray ionization.
      The ions thus formed have been assayed by IRMPD spectroscopy in two different
      spectroscopic domains, namely, the 600-1800 and the 3000-3500 cm(-1) regions
      using either an IR free electron laser or a tabletop OPO/OPA laser source. The
      interpretation of the experimental spectra is aided by density functional theory
      calculations of candidate species and vibrational frequency analyses. Protonated
      benzylamine presents a relatively straightforward instance of a single stable
      conformer, providing a trial case for the adopted approach. Turning to the higher
      homologues, C6H5(CH2)nNH3(+) (n = 2-4), more conformations become accessible. For
      each C6H5(CH2)nNH3(+) ion (n = 2-4), the most stable geometry is characterized by
      cation-pi interactions between the positively charged ammonium group and the
      aromatic pi-electronic system, permitted by the folding of the polymethylene
      chain. The IRMPD spectra of the sampled ions confirm the presence of the folded
      structures by comparison with the calculated IR spectra of the various possible
      conformers. An inspection of the NH stretching region is helpful in this regard. 

PMID- 25061748
TI  - Cloning and characterization of a norbelladine 4'-O-methyltransferase involved in
      the biosynthesis of the Alzheimer's drug galanthamine in Narcissus sp. aff.
      pseudonarcissus.
AB  - Galanthamine is an Amaryllidaceae alkaloid used to treat the symptoms of
      Alzheimer's disease. This compound is primarily isolated from daffodil (Narcissus
      spp.), snowdrop (Galanthus spp.), and summer snowflake (Leucojum aestivum).
      Despite its importance as a medicine, no genes involved in the biosynthetic
      pathway of galanthamine have been identified. This absence of genetic information
      on biosynthetic pathways is a limiting factor in the development of synthetic
      biology platforms for many important botanical medicines. The paucity of
      information is largely due to the limitations of traditional methods for finding
      biochemical pathway enzymes and genes in non-model organisms. A new bioinformatic
      approach using several recent technological improvements was applied to search
      for genes in the proposed galanthamine biosynthetic pathway, first targeting
      methyltransferases due to strong signature amino acid sequences in the proteins.
      Using Illumina sequencing, a de novo transcriptome assembly was constructed for
      daffodil. BLAST was used to identify sequences that contain signatures for plant
      O-methyltransferases in this transcriptome. The program HAYSTACK was then used to
      identify methyltransferases that fit a model for galanthamine biosynthesis in
      leaf, bulb and inflorescence tissues. One candidate gene for the methylation of
      norbelladine to 4'-O-methylnorbelladine in the proposed galanthamine biosynthetic
      pathway was identified. This methyltransferase cDNA was expressed in E. coli and
      the protein purified by affinity chromatography. The resulting protein was found
      to be a norbelladine 4'-O-methyltransferase (NpN4OMT) of the proposed
      galanthamine biosynthetic pathway. 

PMID- 25061751
TI  - Physiological regulation of isocitrate dehydrogenase and the role of 2
      oxoglutarate in Prochlorococcus sp. strain PCC 9511.
AB  - The enzyme isocitrate dehydrogenase (ICDH; EC 1.1.1.42) catalyzes the oxidative
      decarboxylation of isocitrate, to produce 2-oxoglutarate. The incompleteness of
      the tricarboxylic acids cycle in marine cyanobacteria confers a special
      importance to isocitrate dehydrogenase in the C/N balance, since 2-oxoglutarate
      can only be metabolized through the glutamine synthetase/glutamate synthase
      pathway. The physiological regulation of isocitrate dehydrogenase was studied in
      cultures of Prochlorococcus sp. strain PCC 9511, by measuring enzyme activity and
      concentration using the NADPH production assay and Western blotting,
      respectively. The enzyme activity showed little changes under nitrogen or
      phosphorus starvation, or upon addition of the inhibitors DCMU, DBMIB and MSX.
      Azaserine, an inhibitor of glutamate synthase, induced clear increases in the
      isocitrate dehydrogenase activity and icd gene expression after 24 h, and also in
      the 2-oxoglutarate concentration. Iron starvation had the most significant
      effect, inducing a complete loss of isocitrate dehydrogenase activity, possibly
      mediated by a process of oxidative inactivation, while its concentration was
      unaffected. Our results suggest that isocitrate dehydrogenase responds to changes
      in the intracellular concentration of 2-oxoglutarate and to the redox status of
      the cells in Prochlorococcus. 

PMID- 25061753
TI  - The use of directed evolution to create a stable and immunogenic recombinant BCG
      expressing a modified HIV-1 Gag antigen.
AB  - Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for
      HIV. It has a good safety profile, it elicits long-lasting cellular immune
      responses and in addition manufacturing costs are affordable. Despite these
      advantages it is often difficult to express viral antigens in BCG, which results
      in genetic instability and low immunogenicity. The aim of this study was to
      generate stable recombinant BCG (rBCG) that express high levels of HIV antigens,
      by modification of the HIV genes. A directed evolution process was applied to
      recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent
      protein (GFP). Higher growth rates and increased GFP expression were selected
      for. Through this process a modified Gag antigen was selected. Recombinant BCG
      that expressed the modified Gag (BCG[pWB106] and BCG[pWB206]) were more stable,
      produced higher levels of antigen and grew faster than those that expressed the
      unmodified Gag (BCG[pWB105]). The recombinant BCG that expressed the modified HIV
      1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those
      expressing the unmodified Gag (BCG[pWB105]). Mice primed with 10(7) CFU
      BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with
      a frequency of 1343+/-17 SFU/10(6) splenocytes, 16 fold greater than the response
      induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately
      5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in
      those receiving the MVA-Gag boost alone. In addition mice vaccinated with
      BCG[pWB206] were protected from a surrogate vaccinia virus challenge.

PMID- 25061754
TI  - Repeated oronasal exposure to lipopolysaccharide induced mucosal IgA responses in
      periparturient dairy cows.
AB  - This study investigated the effects of repeated oronasal treatment with
      lipopolysaccharide (LPS) on the humoral immune responses in saliva, vaginal
      mucus, and the plasma markers of the acute phase response in periparturient dairy
      cows. One hundred pregnant Holstein cows were administered either 3 increasing
      doses of LPS (n = 50) as follows: 1) 0.01 ug/kg body weight (BW) on d -28, 2)
      0.05 ug/kg BW on d -25, and -21, and 3) 0.1 ug/kg BW on d -18, and -14, or
      sterile saline solution (controls; n = 50) oronasally for 3 consecutive wk
      starting at 28 d before parturition. Intensive sampling was conducted on thirty
      cows (n = 15/group). Multiple saliva, vaginal mucus and blood samples were
      collected around parturition and analyzed for total immunoglobulin-(Ig)A, plasma
      serum amyloid A (SAA), lipopolysaccharide-binding protein (LBP), anti-LPS IgA,
      IgG, IgM, tumour necrosis factor(TNF)-alpha, and interleukin(IL)-1. Results
      regarding total secretory IgA (sIgA) antibodies showed greater concentrations in
      the saliva and an overall tendency for higher total sIgA in the vaginal mucus of
      the LPS-treated cows. Treatment had no effect on plasma sIgA, IgG, IgM anti-LPS
      antibodies, haptoglobin, SAA, LBP, TNF-alpha, and IL-1. Treatments by time
      interactions were observed for SAA and IL-1 with lowered concentrations of both
      variables in the plasma of LPS-treated cows after parturition. Overall, repeated
      oronasal LPS treatment clearly enhanced total sIgA antibodies in the saliva,
      stimulated their production in vaginal mucus shortly before calving, and lowered
      plasma IL-1 around parturition, but showed limited effects on markers of the
      acute phase response in the plasma in dairy cows around parturition. 

PMID- 25061755
TI  - Screening for intellectual disability using high-resolution CMA technology in a
      retrospective cohort from Central Brazil.
AB  - Intellectual disability is a complex, variable, and heterogeneous disorder,
      representing a disabling condition diagnosed worldwide, and the etiologies are
      multiple and highly heterogeneous. Microscopic chromosomal abnormalities and well
      characterized genetic conditions are the most common causes of intellectual
      disability. Chromosomal Microarray Analysis analyses have made it possible to
      identify putatively pathogenic copy number variation that could explain the
      molecular etiology of intellectual disability. The aim of the current study was
      to identify possible submicroscopic genomic alterations using a high-density
      chromosomal microarray in a retrospective cohort of patients with otherwise
      undiagnosable intellectual disabilities referred by doctors from the public
      health system in Central Brazil. The CytoScan HD technology was used to detect
      changes in the genome copy number variation of patients who had intellectual
      disability and a normal karyotype. The analysis detected 18 CNVs in 60% of
      patients. Pathogenic CNVs represented about 22%, so it was possible to propose
      the etiology of intellectual disability for these patients. Likely pathogenic and
      unknown clinical significance CNVs represented 28% and 50%, respectively.
      Inherited and de novo CNVs were equally distributed. We report the nature of CNVs
      in patients from Central Brazil, representing a population not yet screened by
      microarray technologies. 

PMID- 25061756
TI  - The sequential application of macroalgal biosorbents for the bioremediation of a
      complex industrial effluent.
AB  - Fe-treated biochar and raw biochar produced from macroalgae are effective
      biosorbents of metalloids and metals, respectively. However, the treatment of
      complex effluents that contain both metalloid and metal contaminants presents a
      challenging scenario. We test a multiple-biosorbent approach to bioremediation
      using Fe-biochar and biochar to remediate both metalloids and metals from the
      effluent from a coal-fired power station. First, a model was derived from
      published data for this effluent to predict the biosorption of 21 elements by Fe
      biochar and biochar. The modelled outputs were then used to design biosorption
      experiments using Fe-biochar and biochar, both simultaneously and in sequence, to
      treat effluent containing multiple contaminants in excess of water quality
      criteria. The waste water was produced during ash disposal at an Australian coal
      fired power station. The application of Fe-biochar and biochar, either
      simultaneously or sequentially, resulted in a more comprehensive remediation of
      metalloids and metals compared to either biosorbent used individually. The most
      effective treatment was the sequential use of Fe-biochar to remove metalloids
      from the waste water, followed by biochar to remove metals. Al, Cd, Cr, Cu, Mn,
      Ni, Pb, Zn were reduced to the lowest concentration following the sequential
      application of the two biosorbents, and their final concentrations were predicted
      by the model. Overall, 17 of the 21 elements measured were remediated to, or
      below, the concentrations that were predicted by the model. Both metalloids and
      metals can be remediated from complex effluent using biosorbents with different
      characteristics but derived from a single feedstock. Furthermore, the extent of
      remediation can be predicted for similar effluents using additive models. 

PMID- 25061757
TI  - Improving the safety of Staphylococcus aureus polyvalent phages by their
      production on a Staphylococcus xylosus strain.
AB  - Team1 (vB_SauM_Team1) is a polyvalent staphylococcal phage belonging to the
      Myoviridae family. Phage Team1 was propagated on a Staphylococcus aureus strain
      and a non-pathogenic Staphylococcus xylosus strain used in industrial meat
      fermentation. The two Team1 preparations were compared with respect to their
      microbiological and genomic properties. The burst sizes, latent periods, and host
      ranges of the two derivatives were identical as were their genome sequences.
      Phage Team1 has 140,903 bp of double stranded DNA encoding for 217 open reading
      frames and 4 tRNAs. Comparative genomic analysis revealed similarities to
      staphylococcal phages ISP (97%) and G1 (97%). The host range of Team1 was
      compared to the well-known polyvalent staphylococcal phages phi812 and K using a
      panel of 57 S. aureus strains collected from various sources. These bacterial
      strains were found to represent 18 sequence types (MLST) and 14 clonal complexes
      (eBURST). Altogether, the three phages propagated on S. xylosus lysed 52 out of
      57 distinct strains of S. aureus. The identification of phage-insensitive strains
      underlines the importance of designing phage cocktails with broadly varying and
      overlapping host ranges. Taken altogether, our study suggests that some
      staphylococcal phages can be propagated on food-grade bacteria for biocontrol and
      safety purposes. 

PMID- 25061758
TI  - Development of a freeze-dried fungal wettable powder preparation able to
      biodegrade chlorpyrifos on vegetables.
AB  - Continuous use of the pesticide chlorpyrifos has resulted in harmful
      contaminations in environment and species. Based on a chlorpyrifos-degrading
      fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M
      20711), a fungal wettable powder preparation was developed aiming to efficiently
      remove chlorpyrifos residues from vegetables. The formula was determined to be
      11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of
      primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and
      40% of freeze dried fungi by response surface methodology (RSM). The results of
      quality inspection indicated that the fungal preparation could reach
      manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal
      preparation was determined on pre-harvest cabbage. Compared to the controls
      without fungal preparation, the degradation of chlorpyrifos on cabbages, which
      was sprayed with the fungal preparation, was up to 91% after 7 d. These results
      suggested this freeze-dried fungal wettable powder may possess potential for
      biodegradation of chlorpyrifos residues on vegetables and provide a potential
      strategy for food and environment safety against pesticide residues. 

PMID- 25061759
TI  - Grammatical aspect and event recognition in children's online sentence
      comprehension.
AB  - This study investigated whether or not the temporal information encoded in
      aspectual morphemes can be used immediately by young children to facilitate event
      recognition during online sentence comprehension. We focused on the contrast
      between two grammatical aspectual morphemes in Mandarin Chinese, the perfective
      morpheme -le and the (imperfective) durative morpheme -zhe. The perfective
      morpheme -le is often used to indicate that an event has been completed, whereas
      the durative morpheme -zhe indicates that an event is still in progress or
      continuing. We were interested to see whether young children are able to use the
      temporal reference encoded in the two aspectual morphemes (i.e., completed versus
      ongoing) as rapidly as adults to facilitate event recognition during online
      sentence comprehension. Using the visual world eye-tracking paradigm, we tested
      34 Mandarin-speaking adults and 99 Mandarin-speaking children (35 three-year
      olds, 32 four-year-olds and 32 five-year-olds). On each trial, participants were
      presented with spoken sentences containing either of the two aspectual morphemes
      while viewing a visual image containing two pictures, one representing a
      completed event and one representing an ongoing event. Participants' eye
      movements were recorded from the onset of the spoken sentences. The results show
      that both the adults and the three age groups of children exhibited a
      facilitatory effect trigged by the aspectual morpheme: hearing the perfective
      morpheme -le triggered more eye movements to the completed event area, whereas
      hearing the durative morpheme -zhe triggered more eye movements to the ongoing
      event area. This effect occurred immediately after the onset of the aspectual
      morpheme, both for the adults and the three groups of children. This is evidence
      that young children are able to use the temporal information encoded in aspectual
      morphemes as rapidly as adults to facilitate event recognition. Children's eye
      movement patterns reflect a rapid mapping of grammatical aspect onto the temporal
      structures of events depicted in the visual scene. 

PMID- 25061760
TI  - Commentary: imagine a world without abortion stigma.
AB  - This commentary explores what a world without abortion stigma might look like at
      the individual, community and institutional level. The article further
      articulates the need for interdisciplinary collaboration for developing a vision,
      research agenda, and intervention strategy for change.

PMID- 25061761
TI  - Human infections with Borrelia miyamotoi, Japan.
AB  - We confirmed infection of 2 patients with Borrelia miyamotoi in Japan by
      retrospective surveillance of Lyme disease patients and detection of B. miyamotoi
      DNA in serum samples. One patient also showed seroconversion for antibody against
      recombinant glycerophosphodiester phosphodiesterase of B. miyamotoi. Indigenous
      relapsing fever should be considered a health concern in Japan. 

PMID- 25061763
TI  - Nutritional and health benefits of pulses.
AB  - Pulses (beans, peas, and lentils) have been consumed for at least 10 000 years
      and are among the most extensively used foods in the world. A wide variety of
      pulses can be grown globally, making them important both economically as well as
      nutritionally. Pulses provide protein and fibre, as well as a significant source
      of vitamins and minerals, such as iron, zinc, folate, and magnesium, and
      consuming half a cup of beans or peas per day can enhance diet quality by
      increasing intakes of these nutrients. In addition, the phytochemicals, saponins,
      and tannins found in pulses possess antioxidant and anti-carcinogenic effects,
      indicating that pulses may have significant anti-cancer effects. Pulse
      consumption also improves serum lipid profiles and positively affects several
      other cardiovascular disease risk factors, such as blood pressure, platelet
      activity, and inflammation. Pulses are high in fibre and have a low glycemic
      index, making them particularly beneficial to people with diabetes by assisting
      in maintaining healthy blood glucose and insulin levels. Emerging research
      examining the effect of pulse components on HIV and consumption patterns with
      aging populations indicates that pulses may have further effects on health. In
      conclusion, including pulses in the diet is a healthy way to meet dietary
      recommendations and is associated with reduced risk of several chronic diseases.
      Long-term randomized controlled trials are needed to demonstrate the direct
      effects of pulses on these diseases. 

PMID- 25061762
TI  - Co-circulation of Dengue and Chikungunya Viruses, Al Hudaydah, Yemen, 2012.
AB  - We investigated 400 cases of dengue-like illness in persons hospitalized during
      an outbreak in Al Hudaydah, Yemen, in 2012. Overall, 116 dengue and 49
      chikungunya cases were diagnosed. Dengue virus type 2 was the predominant
      serotype. The co-circulation of these viruses indicates that mosquitoborne
      infections represent a public health threat in Yemen. 

PMID- 25061764
TI  - Maintaining hydration with a carbohydrate-electrolyte solution improves
      performance, thermoregulation, and fatigue during an ice hockey scrimmage.
AB  - Research in "stop-and-go" sports has demonstrated that carbohydrate ingestion
      improves performance and fatigue, and that dehydration of ~1.5%-2% body mass (BM)
      loss results in decreased performance, increased fatigue, and increased core
      temperature. The purpose of this investigation was to assess the physiological,
      performance, and fatigue-related effects of maintaining hydration with a
      carbohydrate-electrolyte solution (CES) versus dehydrating by ~2% BM (no fluid;
      NF) during a 70-min ice hockey scrimmage. Skilled male hockey players (n = 14;
      age, 21.3 +/- 0.2 years; BM, 80.1 +/- 2.5 kg; height, 182.0 +/- 1.2 cm)
      volunteered for the study. Subjects lost 1.94% +/- 0.1% BM in NF, and 0.12% +/-
      0.1% BM in CES. Core temperature (Tc) throughout the scrimmage (10-50 min) and
      peak Tc (CES: 38.69 +/- 0.10 vs. NF: 38.92 +/- 0.11  degrees C; p < 0.05) were
      significantly reduced in CES compared with NF. Players in CES had increased mean
      skating speed and time at high effort between 30-50 min of the scrimmage. They
      also committed fewer puck turnovers and completed a higher percentage of passes
      in the last 20 min of play compared with NF. Postscrimmage shuttle skating
      performance was improved in CES versus NF and fatigue was lower following the CES
      trial. The results indicated that ingesting a CES to maintain BM throughout a 70
      min hockey scrimmage resulted in improved hockey performance and
      thermoregulation, and decreased fatigue as compared with drinking no fluid and
      dehydrating by ~2%. 

PMID- 25061765
TI  - Are housestaff identifying malnourished hospitalized medicine patients?
AB  - Clinical nutrition and nutritional assessment are often a neglected component of
      medical school curriculums despite the high prevalence of malnutrition in
      hospitalized patients. This study found that medical housestaff performed
      nutritional assessments in only 4% of admitted patients despite a high rate of
      malnutrition (57%). Survey results show housestaff lack knowledge in the area of
      malnutrition. Medical schools and training programs must place greater emphasis
      of providing qualified physician nutrition specialists to implement effective
      nutrition instruction. 

PMID- 25061766
TI  - The psychosocial and financial impact of non-severe hypoglycemic events on people
      with diabetes: two international surveys.
AB  - OBJECTIVES: To understand the impact of nocturnal and daytime non-severe
      hypoglycemic events on healthcare systems, work productivity and quality of life
      in people with type 1 or type 2 diabetes. METHODS: People with diabetes who
      experienced a non-severe hypoglycemic event in the 4 weeks prior to the survey
      were eligible to participate in a nocturnal and/or daytime hypoglycemia survey.
      Surveys were conducted in Argentina, Australia, Brazil, Israel, Mexico and South
      Africa. RESULTS: In total, 300 respondents were included in nocturnal/daytime
      hypoglycemia surveys (50/participating country/survey). All respondents with type
      1 diabetes and 68%/62% (nocturnal/daytime) with type 2 diabetes were on insulin
      treatment. After an event, 25%/30% (nocturnal/daytime) of respondents decreased
      their insulin dose and 39%/36% (nocturnal/daytime) contacted a healthcare
      professional. In the week after an event, respondents performed an average of
      5.6/6.4 (nocturnal/daytime) additional blood glucose tests. Almost half of the
      respondents (44%) reported that the event had a high impact on the quality of
      their sleep. Among nocturnal survey respondents working for pay, 29% went to work
      late, 16% left work early and 12% reported missing one or more full work days due
      to the surveyed event. In addition, 50%/39% (nocturnal/daytime) indicated that
      the event had a high impact on their fear of future hypoglycemia. CONCLUSIONS:
      The findings suggest that nocturnal and daytime non-severe hypoglycemic events
      have a large financial and psychosocial impact. Diabetes management that
      minimizes hypoglycemia while maintaining good glycemic control may positively
      impact upon the psychological wellbeing of people with diabetes, as well as
      reducing healthcare costs and increasing work productivity.

PMID- 25061768
TI  - Home- and community-based waivers for children with autism: effects on service
      use and costs.
AB  - We examined (a) the associations between Medicaid home and community-based waiver
      participation and service use and expenditures among children with ASD; and (b)
      how states' waiver spending moderates these effects. We used 2005 Medicaid claims
      to identify a sample of children with autism spectrum disorder (ASD). We selected
      two comparison groups who had no waiver participation: (a) children who were
      eligible for Medicaid through disability (disability group), and (b) children who
      had at least one inpatient/long-term care (IP/LT) episode (IP/LT group). Waiver
      participants were less likely to use IP/LT services and had lower associated
      expenditures than the disability group. As states' waiver spending increased,
      waiver participants became increasingly less likely to use IP/LT services. Waiver
      participants had more outpatient visits and associated expenditures; this
      difference increased as state waiver spending increased. Compared with the IP/LT
      group, waiver participants had lower IP/LT expenditures, more outpatient visits,
      and associated expenditures. Higher state waiver generosity increased this effect
      on outpatient visits and expenditures.

PMID- 25061769
TI  - Perceptions of positive contributions and burnout in community developmental
      disability workers.
AB  - Research on staff supporting individuals with intellectual and developmental
      disabilities (IDD) tends to focus on negative aspects of the work. This study
      expanded on previous research on the positive consequences that work in the IDD
      field has on staff using a brief version of the Staff Positive Contributions
      Questionnaire with 926 staff. Factor analysis suggested two factors: General
      positive contributions and Positive work motivation. Positive work motivation was
      associated with high levels of personal accomplishment, but shared limited
      variance with the other two burnout dimensions (emotional exhaustion,
      depersonalization). Findings lend support to the idea that we need to consider
      both positive and negative aspects of work life. This brief scale may be a useful
      index of how staff benefit from their work.

PMID- 25061770
TI  - Formative evaluation of project TEAM (Teens Making Environment and Activity
      Modifications).
AB  - Research documents the negative impact of physical and social environmental
      barriers on engagement in school, work, and the community for youth with
      intellectual and /or developmental disabilities (IDD). Project TEAM (Teens making
      Activity and Environment Modifications) was designed to teach youth to
      systematically identify environmental barriers, generate modification strategies,
      and request accommodations. This formative evaluation used a mixed methods
      expansion design to investigate outcomes, activities, and experiences. Trainees
      had a significant increase in knowledge of environmental factors and modification
      strategies but no changes in applied problem-solving. 76% attained at least one
      goal as measured through goal attainment scaling. Intervention activities ranged
      in quality. Trainees enjoyed the interactive and applied aspects of Project TEAM
      but found some concepts and materials difficult to understand. Lessons learned
      from this comprehensive evaluation can inform future revisions to Project TEAM
      and may be equally relevant for other researchers evaluating programs targeting
      transition-age youth with IDD.

PMID- 25061767
TI  - Why sleep is important for health: a psychoneuroimmunology perspective.
AB  - Sleep has a critical role in promoting health. Research over the past decade has
      documented that sleep disturbance has a powerful influence on the risk of
      infectious disease, the occurrence and progression of several major medical
      illnesses including cardiovascular disease and cancer, and the incidence of
      depression. Increasingly, the field has focused on identifying the biological
      mechanisms underlying these effects. This review highlights the impact of sleep
      on adaptive and innate immunity, with consideration of the dynamics of sleep
      disturbance, sleep restriction, and insomnia on (a) antiviral immune responses
      with consequences for vaccine responses and infectious disease risk and (b)
      proinflammatory immune responses with implications for cardiovascular disease,
      cancer, and depression. This review also discusses the neuroendocrine and
      autonomic neural underpinnings linking sleep disturbance and immunity and the
      reciprocal links between sleep and inflammatory biology. Finally, interventions
      are discussed as effective strategies to improve sleep, and potential
      opportunities are identified to promote sleep health for therapeutic control of
      chronic infectious, inflammatory, and neuropsychiatric diseases. 

PMID- 25061771
TI  - Validity evidence for self-report with assistance to measure physical activity
      behavior in adults with intellectual disabilities.
AB  - Self-reported physical activity (PA) behavior with assistance from a secondary
      source has previously been used with adults with an intellectual disability (ID).
      Limited evidence of reliability and validity have been provided for this
      approach. This study examined evidence of convergent (CV) and discriminant (DV)
      validity for self-report with assistance from a secondary source as a measure of
      PA in adults with ID. PA of 37 participants with ID were assessed using (a) self
      report, (b) accelerometers, and (c) pedometers. The multitrait-multimethod (MTMM)
      analysis was used to evaluate validity. MTMM analysis revealed high reliability
      among variables, low to strong CV, and moderate DV. The study outcomes provide
      initial convergent and discriminant validity evidence for this measure of PA in
      adults with ID.

PMID- 25061772
TI  - Empirically derived model of social outcomes and predictors for adults with ASD.
AB  - This study used data from the National Core Indicators (NCI) Survey to derive an
      empirically validated measurement model for social outcomes and associated
      constructs for both individuals with Autism Spectrum Disorder (ASD) and
      individuals with other disabilities. Items consistent with the survey structure
      of the NCI were selected as initial indicators of the latent constructs Social
      Relationships, Community Inclusion, and Opportunity for Choice in factor
      analyses. Results yielded a novel factor structure that is different from the
      original NCI survey structure. Three factors emerged as a result of these
      analyses: Personal Control, Social Determination, and Social Participation and
      Relationships. The factor structure of each of these constructs was consistent
      although not identical across individuals with ASD and individuals with
      developmental disabilities other than ASD.

PMID- 25061773
TI  - Effect of supported employment on vocational rehabilitation outcomes of
      transition-age youth with intellectual and developmental disabilities: a case
      control study.
AB  - The purpose of this study was to examine the effect of supported employment
      intervention on the employment outcomes of transition-age youth with intellectual
      and developmental disabilities served by the public vocational rehabilitation
      system using a case-control study design. Data for this study were extracted from
      the Rehabilitation Services Administration Case Service Report (RSA-911) database
      for fiscal year 2009. The sample included 23,298 youth with intellectual and
      developmental disabilities aged between 16 and 25 years old at the time of
      application. The classification and regression tree (CART) method was used to
      estimate propensity scores and to adjust for selection bias on the basis of all
      prominent covariates relevant to the dependent variable (i.e., competitive
      employment). Results yielded six homogeneous subgroups, and receipt of supported
      employment was found to increase the employment rates across all of the groups.
      The effect of supported employment was especially strong for youth who were
      Social Security beneficiaries, special education students, and individuals with
      intellectual disabilities or autism who were high school graduates. These
      findings suggest that supported employment is an effective service for enhancing
      the vocational rehabilitation outcomes of young adults and provides valuable
      information for policy makers, health care providers, rehabilitation counselors,
      and educators.

PMID- 25061776
TI  - MR simulation for prostate radiation therapy: effect of coil mounting position on
      image quality.
AB  - OBJECTIVE: To eliminate the effects of body deformation for MR-based prostate
      treatment planning, coil mounts are essential. In this study, we evaluated the
      effect of the coil set-up on image quality. METHODS: A custom-designed pelvic
      shaped phantom was scanned by systematically increasing the anterior body-to-coil
      (BTC) distance from 30 to 90 mm. The image quality near the organs of interest
      was determined in order to characterize the relationship between image quality
      and BTC distance at the critical organ structures. The half intensity reduction
      (HIR) was calculated to determine the sensitivity of each organ structure to the
      BTC distance change. RESULTS: As the BTC distance increased, the uniformity
      reduced at 3% per millimetre. The HIR value indicated that the bladder signal is
      most sensitive to the change in BTC distance. By maintaining a constant BTC
      distance set-up, the intensity uniformity was improved by 28% along the B0
      directions. CONCLUSION: Positioning the MRI coil on mounts can reduce body
      deformation but adversely degrades the image quality. The magnitude of this
      effect has been quantified for prostate MR simulation scanning. The coil needs to
      be positioned not only with a minimal but also uniform BTC distance in order to
      maximize image quality. ADVANCES IN KNOWLEDGE: A method to characterize the
      effect on image quality due to the use of coil mounts was demonstrated. Coil
      mounts whose height can be adjusted individually to keep BTC distance constant
      are necessary to maintain a uniform image across the entire field of view.

PMID- 25061777
TI  - Mycophenolate mofetil versus methotrexate for prevention of graft-versus-host
      disease in people receiving allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is
      associated with improved outcomes for people with various hematologic diseases;
      however, the morbidity and mortality resulting from acute and subsequently
      chronic graft-versus-host disease (GVHD) pose a serious challenge to wider
      applicability of allo-HCT. Intravenous methotrexate in combination with a
      calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for
      the prophylaxis of acute GVHD, but the administration of methotrexate is
      associated with a number of adverse events. Mycophenolate mofetil, in combination
      with a calcineurin inhibitor, has been used extensively in people undergoing allo
      HCT. Conflicting results regarding various clinical outcomes following allo-HCT
      have been observed when comparing mycophenolate mofetil-based regimens against
      methotrexate-based regimens for acute GVHD prophylaxis. OBJECTIVES:  PRIMARY
      OBJECTIVE: to assess the effect of mycophenolate mofetil versus methotrexate for
      prevention of acute GVHD in people undergoing allo-HCT. SECONDARY OBJECTIVES: to
      evaluate the effect of mycophenolate mofetil versus methotrexate for overall
      survival, prevention of chronic GVHD, incidence of relapse, treatment-related
      harms, nonrelapse mortality, and quality of life. SEARCH METHODS: We searched
      Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from
      inception to March 2014. We handsearched conference abstracts from the last two
      meetings (2011 and 2012) of relevant societies in the field. We searched
      ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche
      clinical trial protocol registry (www.roche-trials.com), Australian New Zealand
      Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for
      ongoing trials. SELECTION CRITERIA: Two review authors independently reviewed all
      titles/abstracts and selected full-text articles for inclusion. We included all
      references that reported results of randomized controlled trials (RCTs) of
      mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among
      people undergoing allo-HCT in this review. DATA COLLECTION AND ANALYSIS: Two
      review authors independently extracted data on outcomes from all studies and
      compared prior to data entry and analysis. We expressed results as risk ratios
      (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios
      (HR) and 95% CIs for time-to-event outcomes. We pooled the individual study
      effects using the random-effects model. Estimates lower than one indicate that
      mycophenolate mofetil was favored over methotrexate. MAIN RESULTS: We included
      three trials enrolling 177 participants (174 participants analyzed). All
      participants in the trials by Keihl et al. and Bolwell et al. received
      cyclosporine while all participants enrolled in the trial by Perkins et al.
      received tacrolimus. However, the results did not differ by the type of
      calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no
      evidence for a difference between mycophenolate mofetil versus methotrexate for
      the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value =
      0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17;
      P value = 0.19, low-quality evidence), median days to neutrophil engraftment (HR
      0.77; 95% CI 0.51 to 1.17; P value = 0.23, low-quality evidence), incidence of
      relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low-quality evidence), non
      relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low-quality
      evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value =
      0.62, low-quality evidence). There was low-quality evidence that mycophenolate
      mofetil compared with methotrexate improved platelet engraftment period (HR 0.87;
      95% CI 0.81 to 0.93; P value < 0.0001, low-quality evidence). There was low
      quality evidence that mycophenolate mofetil compared with methotrexate resulted
      in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value
      = 0.0006, low-quality evidence), use of parenteral nutrition (RR 0.48; 95% CI
      0.26 to 0.91; P value = 0.02, low-quality evidence), and medication for pain
      control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low-quality evidence).
      Overall heterogeneity was not detected in the analysis except for the outcome of
      neutrophil engraftment. None of the included studies reported any outcomes
      related to quality of life. Overall quality of evidence was low. AUTHORS'
      CONCLUSIONS: The use of mycophenolate mofetil compared with methotrexate for
      primary prevention of GVHD seems to be associated with a more favorable toxicity
      profile, without an apparent compromise on disease relapse, transplant-associated
      mortality, or overall survival. The effects on incidence of GVHD between people
      receiving mycophenolate mofetil compared with people receiving methotrexate were
      uncertain. There is a need for additional high-quality RCTs to determine the
      optimal GVHD prevention strategy. Future studies should take into account a
      comprehensive view of clinical benefit, including measures of morbidity, symptom
      burden, and healthcare resource utilization associated with interventions.

PMID- 25061781
TI  - Recent advances and remaining challenges for the spectroscopic detection of
      explosive threats.
AB  - In 2010, the U.S. Army initiated a program through the Edgewood Chemical
      Biological Center to identify viable spectroscopic signatures of explosives and
      initiate environmental persistence, fate, and transport studies for trace
      residues. These studies were ultimately designed to integrate these signatures
      into algorithms and experimentally evaluate sensor performance for explosives and
      precursor materials in existing chemical point and standoff detection systems.
      Accurate and validated optical cross sections and signatures are critical in
      benchmarking spectroscopic-based sensors. This program has provided important
      information for the scientists and engineers currently developing trace-detection
      solutions to the homemade explosive problem. With this information, the
      sensitivity of spectroscopic methods for explosives detection can now be
      quantitatively evaluated before the sensor is deployed and tested. 

PMID- 25061778
TI  - Patient question-asking about glaucoma and glaucoma medications during videotaped
      medical visits.
AB  - We applied the ecologic model of communication in medical consultations to
      examine how patient, physician, and situational/contextual factors are associated
      with whether patients ask one or more questions about glaucoma and glaucoma
      medications during visits to ophthalmologists. Patients with glaucoma who were
      newly prescribed or already on glaucoma medications were recruited at six
      ophthalmology clinics. Patients' visits with their doctors were video-recorded
      and patients were interviewed after visits. Generalized estimating equations were
      used to analyze the data. Two hundred and seventy-nine patients participated.
      Patients asked one or more questions about glaucoma during 59% of visits and
      about glaucoma medications during 48% of visits. Patients who were newly
      prescribed glaucoma medications were significantly more likely to ask one or more
      questions about glaucoma and glaucoma medications. Whether providers asked
      patients if they had questions was not significantly associated with patient
      question-asking. Patients were significantly more likely to ask older providers
      questions about glaucoma medications and female providers questions about
      glaucoma. Eye care providers should encourage glaucoma patients to ask questions
      during their medical visits. 

PMID- 25061782
TI  - Determination using synchrotron radiation-based Fourier transform infrared
      microspectroscopy of putative stem cells in human adenocarcinoma of the
      intestine: corresponding benign tissue as a template.
AB  - The epithelial-cell layer lining the two morphologically and functionally
      distinct segments of the mammalian intestinal tract, small intestine, and colon
      is constantly being renewed. This renewal is necessitated by a harsh lumen
      environment and is hypothesized to be driven by a small population of stem cells
      (SCs) that are believed to reside at the base of intestinal crypts. A lack of
      specific markers has hampered previous attempts to identify their exact location.
      We obtained tissue sections containing small intestine and colon crypts derived
      from normal (benign) or adenocarcinoma (AC) human intestine. The samples were
      floated onto BaF2 windows and analyzed using synchrotron radiation-based Fourier
      transform infrared microspectroscopy via an aperture size of 10 * 10 MUm. Derived
      infrared (IR) spectral data was then analyzed using principal component analysis
      and/or linear discriminant analysis. Hypothesized cell types (as a function of
      aperture location along the length of individual crypts) within benign crypts
      were classed based on exploratory unsupervised IR spectral point clustering.
      Scores plots derived from individual small intestine crypts consistently
      generated one or two distinct spectra that clustered away from the remaining cell
      categories; these were retrospectively classed as "distinct base region" spectra.
      In these plots, a clear progression of locations along crypt lengths designated
      as from putative stem cells (SCs) to transit-amplifying (TA) cells to terminally
      differentiated (TD) cells was observed in benign small intestine and colon
      crypts. This progression of spectral points was crypt specific, pointing away
      from a unifying cell lineage model in human intestinal crypts. On comparison of
      AC-derived spectra versus corresponding benign, a subpopulation of AC-derived
      spectra suggested a putative SC-like spectral fingerprint; remaining IR spectra
      were classed as exhibiting TA cell-like or TD cell-like spectral characteristics.
      These observations could point to a cancer SC phenotype; an approach capable of
      identifying their in situ location has enormous therapeutic applications. 

PMID- 25061783
TI  - Discrimination among melanoma, nevi, and normal skin by using synchronous
      luminescence spectroscopy.
AB  - Novel optical spectroscopy and imaging methods may be valuable in the early
      detection of cancer. This paper reports differences in the luminescence responses
      of pigmented skin lesions (melanomas and nevi) and apparently normal non
      pigmented human skin, based on analyses of synchronous luminescence spectroscopy
      measurements. Measurements were performed in the excitation range of 330-545 nm,
      with synchronous intervals varying from 30-120 nm. Normal skin, nevi, and
      melanomas differ in the way they fluoresce, and these differences are more
      distinct in the synchronous fluorescence spectra than in the conventional
      emission and excitation spectra. The differences in the fluorescence
      characteristics of pigmented and normal skin samples were ascribed to differences
      in concentrations of endogenous fluorophores and chromophores. Principal
      component and linear discriminant analysis of the synchronous spectra measured at
      different synchronous intervals showed that the greatest variance among the
      sample groups was at the 70 nm interval spectra. These spectra were then used to
      create partial least squares discriminant analysis-based classification models.
      Evaluation of the quality of these models from the receiver operating
      characteristic curves showed they performed well, with a maximum value of 1 for
      the area under the curve for melanoma detection. Hence, synchronous luminescence
      spectroscopy coupled with statistical methods may be advantageous in the early
      detection of skin cancer. 

PMID- 25061784
TI  - Soil organic carbon content estimation with laboratory-based visible-near
      infrared reflectance spectroscopy: feature selection.
AB  - This study, with Yixing (Jiangsu Province, China) and Honghu (Hubei Province,
      China) as study areas, aimed to compare the successive projection algorithm (SPA)
      and the genetic algorithm (GA) in spectral feature selection for estimating soil
      organic carbon (SOC) contents with visible-near-infrared (Vis-NIR) reflectance
      spectroscopy and further to assess whether the spectral features selected from
      one site could be applied to another site. The SOC content and Vis-NIR
      reflectance spectra of soil samples were measured in the laboratory. Savitzky
      Golay smoothing and log10(1/R) (R is reflectance) were used for spectral
      preprocessing. The reflectance spectra were resampled using different spacing
      intervals ranging from 2 to 10 nm. Then, SPA and GA were conducted for selecting
      the spectral features of SOC. Partial least square regression (PLSR) with full
      spectrum PLSR and the spectral features selected by SPA (SPA-PLSR) and GA (GA
      PLSR) were calibrated and validated using independent datasets, respectively.
      Moreover, the spectral features selected from one study area were applied to
      another area. Study results showed that, for the two study areas, the SPA-PLSR
      and GA-PLSR improved estimation accuracies and reduced spectral variables
      compared with the full spectrum PLSR in estimating SOC contents; GA-PLSR obtained
      better estimation results than SPA-PLSR, whereas SPA was simpler than GA, and the
      spectral features selected from Yixing could be well applied to Honghu, but not
      the reverse. These results indicated that the SPA and GA could reduce the
      spectral variables and improve the performance of PLSR model and that GA
      performed better than SPA in estimating SOC contents. However, SPA is simpler and
      time-saving compared with GA in selecting the spectral features of SOC. The
      spectral features selected from one dataset could be applied to a target dataset
      when the dataset contains sufficient information adequately describing the
      variability of samples of the target dataset. 

PMID- 25061785
TI  - Dual-wavelength Y-branch distributed Bragg reflector diode laser at 785
      nanometers for shifted excitation Raman difference spectroscopy.
AB  - A dual-wavelength Y-branch distributed Bragg reflector (DBR) diode laser at 785
      nm is presented as an excitation light source for shifted excitation Raman
      difference spectroscopy (SERDS). The monolithic device was realized with deeply
      etched surface DBR gratings using one-step epitaxy. An optical output power of
      140 mW was obtained in continuous-wave (CW) operation for each laser cavity, with
      emission wavelengths of the device at 784.50 and 785.12 nm. A spectral width of
      the laser emission of 30 pm (0.5 cm(-1)), including 95% of optical power, was
      measured. The mean spectral distance of both excitation lines is 0.63 nm (10.2
      cm(-1)) over the whole operating range. Raman experiments using polystyrene as
      the test sample and ambient light as the interference source were carried out and
      demonstrate the suitability of the dual-wavelength diode laser for SERDS. 

PMID- 25061786
TI  - Two-dimensional correlation spectroscopy (2D-COS) variable selection for near
      infrared microscopy discrimination of meat and bone meal in compound feed.
AB  - This article presents a novel method for combining auto-peak and cross-peak
      information for sensitive variable selection in synchronous two-dimensional
      correlation spectroscopy (2D-COS). This variable selection method is then applied
      to the case of near-infrared (NIR) microscopy discrimination of meat and bone
      meal (MBM). This is of important practical value because MBM is currently banned
      in ruminate animal compound feed. For the 2D-COS analysis, a set of NIR
      spectroscopy data of compound feed samples (adulterated with varying
      concentrations of MBM) was pretreated using standard normal variate and
      detrending (SNVD) and then mapped to the 2D-COS synchronous matrix. For the auto
      peak analysis, 12 main sensitive variables were identified at 6852, 6388, 6320,
      5788, 5600, 5244, 4900, 4768, 4572, 4336, 4256, and 4192 cm(-1). All these
      variables were assigned their specific spectral structure and chemical component.
      For the cross-peak analysis, these variables were divided into two groups, each
      group containing the six sensitive variables. This grouping resulted in a
      correlation between the spectral variables that was in accordance with the
      chemical-component content of the MBM and compound feed. These sensitive
      variables were then used to build a NIR microscopy discrimination model, which
      yielded a 97% correct classification. Moreover, this method detected the presence
      of MBM when its concentration was less than 1% in an adulterated compound feed
      sample. The concentration-dependent 2D-COS-based variable selection method
      developed in this study has the unique advantages of (1) introducing an
      interpretive aspect into variable selection, (2) substantially reducing the
      complexity of the computations, (3) enabling the transferability of the results
      to discriminant analysis, and (4) enabling the efficient compression of spectral
      data. 

PMID- 25061787
TI  - Robust calibration transfer in noninvasive ethanol measurements, Part I:
      Mathematical basis for spectral distortions in Fourier transform near-infrared
      spectroscopy (FT-NIR).
AB  - Multivariate calibration transfer in spectroscopy is an active area of interest.
      Many current approaches rely on the measurement of a subset of calibration
      samples on each instrument produced, an approach that can be impractical in many
      applications. Furthermore, such methods attempt to model implicitly, rather than
      explicitly, interinstrument differences. In Part I of this work, a Fourier
      transform near-infrared spectroscopy (FT-NIR) system designed to perform
      noninvasive ethanol measurements is discussed. Optical distortions caused by self
      apodization, shear, and off-axis detector field of view (FOV) are examined and
      equations describing their effects are given. The effects of shear and off-axis
      detector FOV are shown to yield nonlinear distortions of the amplitude and
      wavenumber axes of measured spectra that cannot be accommodated by typical
      wavenumber calibration procedures or background correction. The distortions
      forecast by these equations are verified using laboratory measurements, and an
      analysis of the spectral complexity caused by the distortions is presented. The
      theoretical and experimental aspects presented in Part I are incorporated into a
      new calibration transfer method whose benefits are illustrated in Part II using
      noninvasive alcohol measurements. Although this work discusses a specific FT-NIR
      instrument and application, the methods developed form a general framework for
      modeling the distortions of other types of optical spectrometers to improve
      instrument standardization and multivariate calibration transfer. 

PMID- 25061788
TI  - Robust calibration transfer in noninvasive ethanol measurements, Part II:
      Modification of instrument measurements by incorporation of expert knowledge
      (MIMIK).
AB  - Several calibration transfer methods require measurement of a subset of the
      calibration samples on each future instrument, which is impractical in some
      applications. Another consideration is that these methods model inter-instrument
      spectral differences implicitly rather than explicitly. The present work argues
      that explicit knowledge of the origins of inter-instrument spectral distortions
      can benefit calibration transfer during the fabrication and assembly of
      instrumentation, the formation of the multivariate regression, and its subsequent
      transfer to future instruments. In Part I of this work, a Fourier transform near
      infrared system designed to perform noninvasive ethanol measurements was
      discussed and equations describing the optical distortions caused by self
      apodization, retroreflector misalignment, and off-axis detector field of view
      were provided and examined using laboratory measurements. The spectral
      distortions were shown to be nonlinear in the amplitude and wavenumber domains,
      and thus cannot be compensated by simple wavenumber calibration procedures or
      background correction. Part II presents a calibration transfer method that
      combines in vivo data with controlled amounts of optical distortions in order to
      develop a multivariate regression model that is robust to instrument variation.
      Evaluation of the method using clinical data showed improved measurement
      accuracy, outlier detection, and generalization to future instruments relative to
      simple background correction. 

PMID- 25061789
TI  - Response mechanism of the phase transitions of poly(n-isopropylacrylamide-co
      benzo-18-crown-6-acrylamide) using infrared spectroscopy.
AB  - The thermal and ionic effects on the phase transitions of poly(N
      isopropylacrylamide) (PNIPAAm) and its copolymer with benzo-18-crown-6
      acrylamide, poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNIPAAm
      co-BCAm), were investigated using infrared (IR) spectral variations of methyl
      (CH3), C=O, and amine (NH) groups. Subsequently, perturbation correlation moving
      window two-dimensional correlation infrared spectroscopy (PCMW 2D-IR) was applied
      to clarify the differences in the phase-transition mechanisms of the polymers.
      The dominant influence on the phase-transition mechanism of PNIPAAm is whether
      the anion is evenly distributed in the bulk solution. The results show that the
      phase transition shifts to a lower temperature with increasing barium chloride
      (BaCl2) concentrations. In addition, the effect of the anion on the chemical
      group is homogeneous upon heating. As a result, the relevant transition
      temperature ranges have remain approximately constant. In contrast, the dominant
      influence on the phase-transition mechanism of PNIPAAm-co-BCAm is the
      interactions of the polymer chains with barium ions (Ba(2+)). The hydrophilic
      BCAm-Ba(2+) complexes distributed in the PNIPAAm-co-BCAm chain prevent the water
      molecules from leaving the polymer chains, which leads to an increase in the
      transition temperature and the complicated variation of the transition
      temperature range, as environmental stimuli-response behavior, with increasing
      BaCl2 concentrations. 

PMID- 25061790
TI  - Influence of protein size on surface-enhanced Raman scattering (SERS) spectra in
      binary protein mixtures.
AB  - The size-dependent interactions of eight blood proteins with silver nanoparticles
      (AgNPs) in their binary mixtures were investigated using surface-enhanced Raman
      scattering (SERS). Principal component analysis (PCA) was performed on the SERS
      spectra of each binary mixture, and the differentiation ability of the mixtures
      was tested. It was found that the effect of relative concentration change on the
      SERS spectra of the binary mixtures of small proteins could be detected using
      PCA. However, this change was not observed with the binary mixtures of large
      proteins. This study demonstrated that the relative interactions of the smaller
      proteins with an average size of 50 nm AgNPs smaller than the large proteins
      could be monitored, and this information can be used for the detection of
      proteins in protein mixtures. 

PMID- 25061791
TI  - Temperature profile retrieval in axisymmetric combustion plumes using multilayer
      perceptron modeling and spectral feature selection in the infrared CO2 emission
      band.
AB  - In this work, a methodology based on the combined use of a multilayer perceptron
      model fed using selected spectral information is presented to invert the
      radiative transfer equation (RTE) and to recover the spatial temperature profile
      inside an axisymmetric flame. The spectral information is provided by the
      measurement of the infrared CO2 emission band in the 3-5 MUm spectral region. A
      guided spectral feature selection was carried out using a joint criterion of
      principal component analysis and a priori physical knowledge of the radiative
      problem. After applying this guided feature selection, a subset of 17 wavenumbers
      was selected. The proposed methodology was applied over synthetic scenarios.
      Also, an experimental validation was carried out by measuring the spectral
      emission of the exhaust hot gas plume in a microjet engine with a Fourier
      transform-based spectroradiometer. Temperatures retrieved using the proposed
      methodology were compared with classical thermocouple measurements, showing a
      good agreement between them. Results obtained using the proposed methodology are
      very promising and can encourage the use of sensor systems based on the spectral
      measurement of the CO2 emission band in the 3-5 MUm spectral window to monitor
      combustion processes in a nonintrusive way. 

PMID- 25061792
TI  - Detection of deoxyribonucleic acid (DNA) targets using polymerase chain reaction
      (PCR) and paper surface-enhanced Raman spectroscopy (SERS) chromatography.
AB  - Surface-enhanced Raman spectroscopy (SERS) enables multiplex detection of
      analytes using simple, portable equipment consisting of a single excitation
      source and detector. Thus, in theory, SERS is ideally suited to replace
      fluorescence in assays that screen for numerous deoxyribonucleic acid (DNA)
      targets, but in practice, SERS-based assays have suffered from complexity and
      elaborate processing steps. Here, we report an assay in which a simple inkjet
      fabricated plasmonic paper device enables SERS-based detection of multiple DNA
      targets within a single polymerase chain reaction (PCR). In prior work, we
      demonstrated the principles of chromatographic separation and SERS-based
      detection on inkjet-fabricated plasmonic paper. The present work extends that
      capability for post-PCR gene sequence detection. In this design, hydrolysis DNA
      probes with 5' Raman labels are utilized; if the target is present, the probe is
      hydrolyzed during PCR, freeing the reporter. After applying the PCR sample to a
      paper SERS device, an on-device chromatographic separation and concentration is
      conducted to discriminate between hydrolyzed and intact probes. SERS is then used
      to detect the reporter released by the hydrolyzed probes. This simple separation
      and detection on paper eliminates the need for complex sample processing steps.
      In this work, we simultaneously detect the methicillin-resistant Staphylococcus
      aureus genes mecA and femB to illustrate the concept. We envision that this
      approach could contribute to the development of multiplex DNA diagnostic tests
      enabling screening for several target sequences within a single reaction, which
      is necessary for cases in which sample volume and resources are limited. 

PMID- 25061793
TI  - A modified transmission tip-enhanced Raman scattering (TERS) setup provides
      access to opaque samples.
AB  - The combination of scanning probe microscopy and Raman spectroscopy enables
      chemical characterization of surfaces at highest spatial resolution. This so
      called tip-enhanced Raman scattering (TERS) can be employed for a variety of
      samples where a label-free characterization or identification of constituents on
      the nanometer scale is pursued. Present TERS setup geometries are always a
      compromise for specific dedicated applications and show different advantages and
      disadvantages: Transmission back-reflection setups, when using immersion
      objectives with a high numerical aperture, intrinsically provide the highest
      collection efficiency but cannot be applied for opaque samples. Those samples
      demand upright setups, at the cost of lower collection efficiency, even though
      very efficient systems using a parabolic mirror for illumination and collection
      have been demonstrated. In this contribution it is demonstrated that the
      incorporation of a dichroic mirror to a transmission TERS setup provides easy
      access to opaque samples without further modification of the setup. 

PMID- 25061794
TI  - Differentiation of aflatoxigenic and non-aflatoxigenic strains of Aspergilli by
      FT-IR spectroscopy.
AB  - Fourier transform infrared spectroscopy (FT-IR) is a well-established and widely
      accepted methodology to identify and differentiate diverse microbial species. In
      this study, FT-IR was used to differentiate 20 strains of ubiquitous and
      agronomically important phytopathogens of Aspergillus flavus and Aspergillus
      parasiticus. By analyzing their spectral profiles via principal component and
      cluster analysis, differentiation was achieved between the aflatoxin-producing
      and nonproducing strains of both fungal species. This study thus indicates that
      FT-IR coupled to multivariate statistics can rapidly differentiate strains of
      Aspergilli based on their toxigenicity. 

PMID- 25061795
TI  - Acoustic communication and sound degradation: how do the individual signatures of
      male and female zebra finch calls transmit over distance?
AB  - BACKGROUND: Assessing the active space of the various types of information
      encoded by songbirds' vocalizations is important to address questions related to
      species ecology (e.g. spacing of individuals), as well as social behavior (e.g.
      territorial and/or mating strategies). Up to now, most of the previous studies
      have investigated the degradation of species-specific related information
      (species identity), and there is a gap of knowledge of how finer-grained
      information (e.g. individual identity) can transmit through the environment. Here
      we studied how the individual signature coded in the zebra finch long distance
      contact call degrades with propagation. METHODOLOGY: We performed sound
      transmission experiments of zebra finches' distance calls at various propagation
      distances. The propagated calls were analyzed using discriminant function
      analyses on a set of analytical parameters describing separately the spectral and
      temporal envelopes, as well as on a complete spectrographic representation of the
      signals. RESULTS/CONCLUSION: We found that individual signature is remarkably
      resistant to propagation as caller identity can be recovered even at distances
      greater than a hundred meters. Male calls show stronger discriminability at long
      distances than female calls, and this difference can be explained by the more
      pronounced frequency modulation found in their calls. In both sexes, individual
      information is carried redundantly using multiple acoustical features.
      Interestingly, features providing the highest discrimination at short distances
      are not the same ones that provide the highest discrimination at long distances.

PMID- 25061796
TI  - Pain management in ambulatory surgery-a review.
AB  - Day surgery, coming to and leaving the hospital on the same day as surgery as
      well as ambulatory surgery, leaving hospital within twenty-three hours is
      increasingly being adopted. There are several potential benefits associated with
      the avoidance of in-hospital care. Early discharge demands a rapid recovery and
      low incidence and intensity of surgery and anaesthesia related side-effects; such
      as pain, nausea and fatigue. Patients must be fit enough and symptom intensity so
      low that self-care is feasible in order to secure quality of care. Preventive
      multi-modal analgesia has become the gold standard. Administering paracetamol,
      NSIADs prior to start of surgery and decreasing the noxious influx by the use of
      local anaesthetics by peripheral block or infiltration in surgical field prior to
      incision and at wound closure in combination with intra-operative fast acting
      opioid analgesics, e.g., remifentanil, have become standard of care. Single
      preoperative 0.1 mg/kg dose dexamethasone has a combined action, anti-emetic and
      provides enhanced analgesia. Additional alpha-2-agonists and/or gabapentin or
      pregabalin may be used in addition to facilitate the pain management if patients
      are at risk for more pronounced pain. Paracetamol, NSAIDs and rescue oral opioid
      is the basic concept for self-care during the first 3-5 days after common
      day/ambulatory surgical procedures. 

PMID- 25061797
TI  - Computational design of nucleic acid feedback control circuits.
AB  - The design of synthetic circuits for controlling molecular-scale processes is an
      important goal of synthetic biology, with potential applications in future in
      vitro and in vivo biotechnology. In this paper, we present a computational
      approach for designing feedback control circuits constructed from nucleic acids.
      Our approach relies on an existing methodology for expressing signal processing
      and control circuits as biomolecular reactions. We first extend the methodology
      so that circuits can be expressed using just two classes of reactions: catalysis
      and annihilation. We then propose implementations of these reactions in three
      distinct classes of nucleic acid circuits, which rely on DNA strand displacement,
      DNA enzyme and RNA enzyme mechanisms, respectively. We use these implementations
      to design a Proportional Integral controller, capable of regulating the output of
      a system according to a given reference signal, and discuss the trade-offs
      between the different approaches. As a proof of principle, we implement our
      methodology as an extension to a DNA strand displacement software tool, thus
      allowing a broad range of nucleic acid circuits to be designed and analyzed
      within a common modeling framework. 

PMID- 25061798
TI  - Synthesis of crystalline molecular gyrotops and phenylene rotation inside the
      cage.
AB  - Phenylene-bridged macrocage molecules were synthesized as molecular gyrotops
      because the rotor can rotate even in a crystal. The chain-length-dependent
      properties of the molecular gyrotops were investigated in order to explore the
      potential to create new molecular materials. The formation of the cage in the
      synthesis of each molecular gyrotop depended on the length of the alkyl chains of
      the precursor. The rotation modes and energy barriers for phenylene rotation
      inside the crystals of the molecular gyrotops were changed by varying the chain
      length of the cage. 

PMID- 25061799
TI  - Efficient synthesis of Empagliflozin, an inhibitor of SGLT-2, utilizing an AlCl3
      promoted silane reduction of a beta-glycopyranoside.
AB  - An efficient production synthesis of the SGLT-2 inhibitor Empagliflozin (5) from
      acid 1 is described. The key tactical stage involves I/Mg exchange of aryl iodide
      2 followed by addition to glucono lactone 3 in THF. Subsequent in situ treatment
      of the resulting lactol with HCl in MeOH produces beta-anomeric methyl
      glycopyranoside 4 which is, without isolation, directly reduced with Et3SiH
      mediated by AlCl3 as a Lewis acid in CH2Cl2/MeCN to afford 5 in 50% overall
      yield. The process was implemented for production on a metric ton scale for
      commercial launch. 

PMID- 25061800
TI  - Polymorph control of luminescence properties in molecular crystals of a platinum
      and organoarsenic complex and formation of stable one-dimensional nanochannel.
AB  - The mononuclear diiodoplatinum(II) complex (trans-PtI2(cis-DHDAMe)2), where cis
      DHDAMe = cis-1,4-dihydro-1,4-dimethyl-2,3,5,6-tetrakis(methoxycarbonyl)-1,4
      diarsinine, forms three different crystalline polymorphs that can be either
      concomitantly or separately obtained on varying the recrystallization conditions.
      Cubic red crystals (alpha-phase) and red-orange needles (beta-phase) exhibit
      solid-state red emissions at room temperature. Cubic red crystals of the gamma
      phase show no solid-state emission at room temperature. All crystalline
      structures were confirmed by X-ray crystallography. Room-temperature strongly
      luminescent crystals (alpha-phase) (lambdaem = 657 nm, Phi = 0.52) have a
      triclinic P1 (No. 2) structure and no voids in the crystal structure. Red-orange
      needle-shaped crystals of the beta-phase exhibit moderate red luminescence
      (lambdaem = 695 nm, Phi = 0.09) at room temperature and have a trigonal, R3 (No.
      148), structure. In the needlelike crystals of the beta-phase, stable hexagonal
      arrays of nanoporous channels, 5.0 A in diameter, are formed. Room-temperature
      nonluminescent crystals (gamma-phase) have an orthorhombic, Pbca (No. 61),
      structure with a void volume that is 4.9% of the total crystal volume. After
      heating the alpha-phase crystals at 150  degrees C for 2 min, a powder XRD
      pattern different from the original crystal is obtained, and its solid-state
      emission at room temperature decreased. After heating the beta-phase crystals at
      150  degrees C for 2 min, the emission wavelength and the quantum yield of the
      solid-state emission at room temperature and the powder XRD pattern are the same
      as those of the alpha-phase after heating at 150  degrees C. A crystal-to-crystal
      transition triggered by the thermal stimulus produces a different stable
      polymorph of the mononuclear diiodoplatinum(II) complex. The one-dimensional
      nanoporous crystals encapsulated iodine without distorting the crystal packing.

PMID- 25061802
TI  - Proanthocyanidins in wild sea buckthorn (Hippophae rhamnoides) berries analyzed
      by reversed-phase, normal-phase, and hydrophilic interaction liquid
      chromatography with UV and MS detection.
AB  - A rapid and sensitive method for profiling of proanthocyanidins (PAs) of sea
      buckthorn (Hippophae rhamnoides) berries was established based on aqueous,
      acidified acetone extraction. The extract was purified by Sephadex column
      chromatography and analyzed using reversed-phase, normal-phase, and hydrophilic
      interaction liquid chromatography (HILIC). Negative ion electrospray ionization
      mass spectrometry (ESI-MS) in single ion recording (SIR) and full scan modes
      combined with UV detection were used to define the combinations and ratios of PA
      oligomer classes. PAs with degree of polymerization from 2 to 11 were detected by
      HILIC-ESI-MS. Quantification of dimeric, trimeric, and tetrameric PAs was carried
      out with ESI-MS-SIR, and their molar proportions were 40, 40, and 20%,
      respectively. Only B-type PAs were found, and (epi)gallocatechins were the main
      monomeric units. More than 60 combinations of (epi)catechins and
      (epi)gallocatechins of proanthocyanidin dimers and trimers were found. A majority
      of the PAs were shown to be higher polymers based on the HILIC-UV analysis. 

PMID- 25061803
TI  - Discovery of potent cytotoxic ortho-aryl chalcones as new scaffold targeting
      tubulin and mitosis with affinity-based fluorescence.
AB  - A series of new ortho-aryl chalcones have been designed and synthesized. Many of
      these compounds were found to exhibit significant antiproliferation activity
      toward a panel of cancer cell lines. Selected compounds show potent cytotoxicity
      against several drug resistant cell lines including paclitaxel (Taxol) resistant
      human ovarian carcinoma cells, vincristine resistant human ileocecum carcinoma
      cells, and doxorubicin resistant human breast carcinoma cells. Further
      investigation revealed that active analogues could inhibit the microtubule
      polymerization by binding to colchicine site and thus induce multipolar mitosis,
      G2/M phase arrest, and apoptosis of cancer cells. Furthermore, affinity-based
      fluorescence enhancement was observed during the binding of active compounds with
      tubulin, which greatly facilitated the determination of tubulin binding site of
      the compounds. Finally, selected compound 26 was found to exhibit obvious in vivo
      antitumor activity in A549 tumor xenografts model. Our systematic studies implied
      a new scaffold targeting tubulin and mitosis for novel antitumor drug discovery. 

PMID- 25061804
TI  - Rapid synthesis of polyprenylated acylphloroglucinol analogs via dearomative
      conjunctive allylic annulation.
AB  - Polyprenylated acylphloroglucinols (PPAPs) are structurally complex natural
      products with promising biological activities. Herein, we present a biosynthesis
      inspired, diversity-oriented synthesis approach for rapid construction of PPAP
      analogs via double decarboxylative allylation (DcA) of acylphloroglucinol
      scaffolds to access allyl-desoxyhumulones followed by dearomative conjunctive
      allylic alkylation (DCAA). 

PMID- 25061806
TI  - Gaze Stabilization Test Asymmetry Score as an Indicator of Previous Concussion in
      a Cohort of Collegiate Football Players.
AB  - OBJECTIVE: Vestibular dysfunction may lead to decreased visual acuity with head
      movements, which may impede athletic performance and result in injury. The
      purpose of this study was to test the hypothesis that athletes with history of
      concussion would have differences in gaze stabilization test (GST) as compared
      with those without a history of concussion. DESIGN: Cross-sectional, descriptive.
      SETTING: University Athletic Medicine Facility. PARTICIPANTS: Fifteen collegiate
      football players with a history of concussion, 25 collegiate football players
      without a history of concussion. INTERVENTION: Participants completed the
      dizziness handicap inventory (DHI), static visual acuity, perception time test,
      active yaw plane GST, stability evaluation test (SET), and a bedside oculomotor
      examination. MAIN OUTCOME MEASURES: Independent samples t test was used to
      compare GST, SET, and DHI scores per group, with Bonferroni-adjusted alpha at P <
      0.01. Receiver operating characteristic curve analysis and area under the curve
      (AUC) were used to assess the clinical performance of the GST and SET. RESULTS:
      Athletes with previous concussion had a larger GST asymmetry score [mean (M) =
      12.40, SD = 9.09] than those without concussion (M = 4.92, SD = 4.67; t (18.70) =
      -2.955, P = 0.008, 95% CI, -12.79 to -2.18, d = -1.37). Clinical performance of
      the GST (AUC = 0.77) was better than the SET (AUC = 0.61). CONCLUSIONS: Results
      suggest peripheral vestibular or vestibular-visual interaction deficits in
      collegiate athletes with a history of concussion. The results support further
      research on the use of GST for sport-related concussion evaluation and
      monitoring. CLINICAL RELEVANCE: Inclusion of objective vestibular tests in the
      concussion protocol may reveal the presence of peripheral vestibular or visual
      vestibular deficits. Therefore, the GST may add an important perspective on the
      effects of concussion.

PMID- 25061805
TI  - Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different
      effects on fracture healing in mice.
AB  - The canonical Wnt/beta-catenin pathway plays a key role in the regulation of bone
      remodeling in mice and humans. Two transmembrane proteins that are involved in
      decreasing the activity of this pathway by binding to extracellular antagonists,
      such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related
      protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5-/-) as well as
      osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe
      osteoporosis occurring at young age. In this study, we analyzed the influence of
      Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture
      healing in mice using flexible and semi-rigid fracture fixation. We demonstrated
      that fracture healing was highly impaired in both mouse genotypes, but that
      impairment was more severe in Col1a1-Krm2 than in Lrp5-/- mice and particularly
      evident in mice in which the more flexible fixation was used. Bone formation was
      more reduced in Col1a1-Krm2 than in Lrp5-/- mice, whereas osteoclast number was
      similarly increased in both genotypes in comparison with wild-type mice. Using
      microarray analysis we identified reduced expression of genes mainly involved in
      osteogenesis that seemed to be responsible for the observed stronger impairment
      of healing in Col1a1-Krm2 mice. In line with these findings, we detected
      decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active
      beta-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a
      significant role in regulating bone formation during fracture healing,
      antagonizing KRM2 might be a therapeutic option to improve fracture healing under
      compromised conditions, such as osteoporosis. 

PMID- 25061807
TI  - Reliability of a Computerized Neurocognitive Test in Baseline Concussion Testing
      of High School Athletes.
AB  - OBJECTIVE: Baseline assessments using computerized neurocognitive tests are
      frequently used in the management of sport-related concussions. Such testing is
      often done on an annual basis in a community setting. Reliability is a
      fundamental test characteristic that should be established for such tests. Our
      study examined the test-retest reliability of a computerized neurocognitive test
      in high school athletes over 1 year. DESIGN: Repeated measures design. SETTING:
      Two American high schools. PARTICIPANTS: High school athletes (N = 117)
      participating in American football or soccer during the 2011-2012 and 2012-2013
      academic years. INTERVENTIONS: All study participants completed 2 baseline
      computerized neurocognitive tests taken 1 year apart at their respective schools.
      The test measures performance on 4 cognitive tasks: identification speed
      (Attention), detection speed (Processing Speed), one card learning accuracy
      (Learning), and one back speed (Working Memory). MAIN OUTCOME MEASURES:
      Reliability was assessed by measuring the intraclass correlation coefficient
      (ICC) between the repeated measures of the 4 cognitive tasks. Pearson and
      Spearman correlation coefficients were calculated as a secondary outcome measure.
      RESULTS: The measure for identification speed performed best (ICC = 0.672; 95%
      confidence interval, 0.559-0.760) and the measure for one card learning accuracy
      performed worst (ICC = 0.401; 95% confidence interval, 0.237-0.542). All tests
      had marginal or low reliability. CONCLUSIONS: In a population of high school
      athletes, computerized neurocognitive testing performed in a community setting
      demonstrated low to marginal test-retest reliability on baseline assessments 1
      year apart. Further investigation should focus on (1) improving the reliability
      of individual tasks tested, (2) controlling for external factors that might
      affect test performance, and (3) identifying the ideal time interval to repeat
      baseline testing in high school athletes. CLINICAL RELEVANCE: Computerized
      neurocognitive tests are used frequently in high school athletes, often within a
      model of baseline testing of asymptomatic individuals before the start of a
      sporting season. This study adds to the evidence that suggests in this population
      such testing may lack sufficient reliability to support clinical decision making.

PMID- 25061808
TI  - Diagnosis of Bartonella henselae prosthetic valve endocarditis in man, France.

PMID- 25061809
TI  - Analyzing genome-wide association studies with an FDR controlling modification of
      the Bayesian Information Criterion.
AB  - The prevailing method of analyzing GWAS data is still to test each marker
      individually, although from a statistical point of view it is quite obvious that
      in case of complex traits such single marker tests are not ideal. Recently
      several model selection approaches for GWAS have been suggested, most of them
      based on LASSO-type procedures. Here we will discuss an alternative model
      selection approach which is based on a modification of the Bayesian Information
      Criterion (mBIC2) which was previously shown to have certain asymptotic
      optimality properties in terms of minimizing the misclassification error.
      Heuristic search strategies are introduced which attempt to find the model which
      minimizes mBIC2, and which are efficient enough to allow the analysis of GWAS
      data. Our approach is implemented in a software package called MOSGWA. Its
      performance in case control GWAS is compared with the two algorithms HLASSO and d
      GWASelect, as well as with single marker tests, where we performed a simulation
      study based on real SNP data from the POPRES sample. Our results show that MOSGWA
      performs slightly better than HLASSO, where specifically for more complex models
      MOSGWA is more powerful with only a slight increase in Type I error. On the other
      hand according to our simulations GWASelect does not at all control the type I
      error when used to automatically determine the number of important SNPs. We also
      reanalyze the GWAS data from the Wellcome Trust Case-Control Consortium and
      compare the findings of the different procedures, where MOSGWA detects for
      complex diseases a number of interesting SNPs which are not found by other
      methods. 

PMID- 25061811
TI  - Structure and IR vibrational spectra of Na8[AlSiO4]6(BH4)2: comparison of theory
      and experiment.
AB  - The structure and IR vibrational spectra of tetrahydroborate sodalite
      (Na8[AlSiO4]6(BH4)2) were calculated using density functional theory (DFT)
      methods. The calculations, performed at the GGA hybrid DFT level yield a close
      agreement with XRD refinements of the structure and allow interpretation of
      observed bands of the enclosed BH4(-) and the framework and, in particular, a
      verification of hydrogen positions (Buhl, J.-C., Gesing, T. M., and Ruscher, C.
      H. Microporous Mesoporous Mater. 2005, 80, 57-63). In a first step, different
      basis sets and functionals were tested on NaBH4 and Na8[AlSiO4]6Cl2. We show that
      accurate treatment of B-H stretching modes requires anharmonic corrections, while
      lattice vibrations are well described within the harmonic approximation.

PMID- 25061810
TI  - Quantitative analysis of T cell receptor complex interaction sites using
      genetically encoded photo-cross-linkers.
AB  - The T cell receptor (TCR)-cluster of differentiation 3 (CD3) signaling complex
      plays an important role in initiation of adaptive immune responses, but weak
      interactions have obstructed delineation of the individual TCR-CD3 subunit
      interactions during T cell signaling. Here, we demonstrate that unnatural amino
      acids (UAA) can be used to photo-cross-link subunits of TCR-CD3 on the cell
      surface. Incorporating UAA in mammalian cells is usually a low efficiency
      process. In addition, TCR-CD3 is composed of eight subunits and both TCR and CD3
      chains are required for expression on the cell surface. Photo-cross-linking of
      UAAs for studying protein complexes such as TCR-CD3 is challenging due to the
      difficulty of transfecting and expressing multisubunit protein complexes in cells
      combined with the low efficiency of UAA incorporation. Here, we demonstrate that
      by systematic optimization, we can incorporate UAA in TCR-CD3 with high
      efficiency. Accordingly, the incorporated UAA can be used for site-specific photo
      cross-linking experiments to pinpoint protein interaction sites, as well as to
      confirm interaction sites identified by X-ray crystallography. We systemically
      compared two different photo-cross-linkers--p-azido-phenylalanine (pAzpa) and H-p
      Bz-Phe-OH (pBpa)--for their ability to map protein subunit interactions in the
      2B4 TCR. pAzpa was found to have higher cross-linking efficiency, indicating that
      optimization of the selection of the most optimal cross-linker is important for
      correct identification of protein-protein interactions. This method is therefore
      suitable for studying interaction sites of large, dynamic heteromeric protein
      complexes associated with various cellular membrane systems.

PMID- 25061812
TI  - Silencer of death domains controls cell death through tumour necrosis factor
      receptor 1 and caspase-10 in acute lymphoblastic leukemia.
AB  - Resistance to apoptosis remains a significant problem in drug resistance and
      treatment failure in malignant disease. NO-aspirin is a novel drug that has
      efficacy against a number of solid tumours, and can inhibit Wnt signaling, and
      although we have shown Wnt signaling to be important for acute lymphoblastic
      leukemia (ALL) cell proliferation and survival inhibition of Wnt signaling does
      not appear to be involved in the induction of ALL cell death. Treatment of B
      lineage ALL cell lines and patient ALL cells with NO-aspirin induced rapid
      apoptotic cell death mediated via the extrinsic death pathway. Apoptosis was
      dependent on caspase-10 in association with the formation of the death-inducing
      signaling complex (DISC) incorporating pro-caspase-10 and tumor necrosis factor
      receptor 1 (TNF-R1). There was no measurable increase in TNF-R1 or TNF-alpha in
      response to NO-aspirin, suggesting that the process was ligand-independent.
      Consistent with this, expression of silencer of death domain (SODD) was reduced
      following NO-aspirin exposure and lentiviral mediated shRNA knockdown of SODD
      suppressed expansion of transduced cells confirming the importance of SODD for
      ALL cell survival. Considering that SODD and caspase-10 are frequently over
      expressed in ALL, interfering with these proteins may provide a new strategy for
      the treatment of this and potentially other cancers. 

PMID- 25061813
TI  - Antibodies against severe fever with thrombocytopenia syndrome virus in healthy
      persons, China, 2013.
AB  - In June 2013, a subclinical infection with severe fever with thrombocytopenia
      syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting
      seroprevalence studies in 6 districts within the province. Of 986 healthy persons
      tested, 71 had IgG antibodies against SFTSV. This finding suggests that most
      natural infections with SFTSV are mild or subclinical. 

PMID- 25061814
TI  - Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new
      paradigm in nanotoxicology.
AB  - The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the
      mechanisms underlying their cytotoxicity remain still largely unclear. Here we
      demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of
      cellular internalization. In particular, if otherwise toxic gold, silver, and
      iron oxide NPs are forced through the cell membrane bypassing any form of active
      mechanism (e.g., endocytosis), no significant cytotoxic effect is registered.
      Pneumatically driven NPs across the cell membrane show a different distribution
      within the cytosol compared to NPs entering the cell by active endocytosis.
      Specifically, they exhibit free random Brownian motions within the cytosol and do
      not accumulate in lysosomes. Results suggest that intracellular accumulation of
      metallic nanoparticles into endo-lysosomal compartments is the leading cause of
      nanotoxicity, due to consequent nanoparticle degradation and in situ release of
      metal ions. 

PMID- 25061815
TI  - Hippocampal effective synchronization values are not pre-seizure indicator
      without considering the state of the onset channels.
AB  - In this paper, a model-based approach is presented to quantify the effective
      synchrony between hippocampal areas from depth-EEG signals. This approach is
      based on the parameter identification procedure of a realistic Multi-Source/Multi
      Channel (MSMC) hippocampal model that simulates the function of different areas
      of hippocampus. In the model it is supposed that the observed signals recorded
      using intracranial electrodes are generated by some hidden neuronal sources,
      according to some parameters. An algorithm is proposed to extract the intrinsic
      (solely relative to one hippocampal area) and extrinsic (coupling coefficients
      between two areas) model parameters, simultaneously, by a Maximum Likelihood (ML)
      method. Coupling coefficients are considered as the measure of effective
      synchronization. This work can be considered as an application of Dynamic Causal
      Modeling (DCM) that enables us to understand effective synchronization changes
      during transition from inter-ictal to pre -ictal state. The algorithm is first
      validated by using some synthetic datasets. Then by extracting the coupling
      coefficients of real depth-EEG signals by the proposed approach, it is observed
      that the coupling values show no significant difference between ictal, pre-ictal
      and inter-ictal states, i.e. either the increase or decrease of coupling
      coefficients has been observed in all states. However, taking the value of
      intrinsic parameters into account, pre-seizure state can be distinguished from
      inter-ictal state. It is claimed that seizures start to appear when there are
      seizure-related physiological parameters on the onset channel, and its coupling
      coefficient toward other channels increases simultaneously. As a result of
      considering both intrinsic and extrinsic parameters as the feature vector, inter
      ictal, pre-ictal and ictal activities are discriminated from each other with an
      accuracy of 91.33% accuracy. 

PMID- 25061816
TI  - Dissociable processes for orientation discrimination learning and contextual
      illusion magnitude.
AB  - Previous research suggests an inverse relationship between human orientation
      discrimination sensitivity and tilt illusion magnitude. To test whether these
      perceptual functions are inherently linked, we measured both orientation
      discrimination sensitivity and the magnitude of the tilt illusion before and
      after participants had been trained for three days on an orientation
      discrimination task. Discrimination sensitivity improved with training and this
      improvement remained one month after the initial learning. However, tilt illusion
      magnitude remained unchanged before and after orientation training, at either
      trained or untrained orientations. Our results suggest that orientation
      discrimination sensitivity and illusion magnitude are not inherently linked. They
      also provide further evidence that, at least for the training periods we
      employed, perceptual learning of orientation discrimination may involve high
      level processes. 

PMID- 25061818
TI  - The mGluR5 antagonist fenobam induces analgesic conditioned place preference in
      mice with spared nerve injury.
AB  - Antagonists of metabotropic glutamate receptors (mGluRs) have the potential to
      act as analgesic drugs that may help alleviate chronic pain. This study was done
      to look at the possible rewarding properties of the mGluR5 antagonist, fenobam,
      in a cognitive assay. Analgesic conditioned place preference (aCPP) was used to
      examine the effects of fenobam (30 mg/kg) and the prototypical mGluR5 antagonist,
      MPEP, and these effects were compared to those of a drug with known analgesic
      properties, morphine (10 mg/kg). In each experiment, one group of mice received
      spared nerve injury (SNI) surgery to model chronic pain; the other group received
      a control sham surgery. Both fenobam and MPEP induced preference in the SNI mice,
      such that SNI mice spent significantly more time in the mGluR5 antagonist-paired
      chamber compared to a vehicle-paired chamber. No such preference developed for
      sham mice. Morphine induced preference in male and female mice in both the SNI
      and sham groups. The results showed that fenobam and MPEP likely reduced on-going
      distress in the SNI mice, causing them to prefer the chamber paired with the drug
      compared to the vehicle-paired chamber. Since sham animals did not prefer the
      drug-paired chamber, these data demonstrate that mGluR5 antagonism is non
      rewarding in the absence of pain-like injury. 

PMID- 25061819
TI  - Galleria mellonella infection model demonstrates high lethality of ST69 and ST127
      uropathogenic E. coli.
AB  - Galleria mellonella larvae are an alternative in vivo model for investigating
      bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from
      five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae.
      Larvae were challenged with a range of inoculum doses to determine the 50% lethal
      dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots.
      Virulence was correlated with carriage of a panel of 29 virulence factors (VF).
      Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming
      units/larvae) showed significantly higher mortality rates than those infected
      with ST73, ST95 and ST131 isolates, killing 50% of the larvae within 24 hours.
      Interestingly, ST131 isolates were the least virulent. We observed that ST127
      isolates are significantly associated with a higher VF-score than isolates of all
      other STs tested (P<=0.0001), including ST69 (P<0.02), but one ST127 isolate
      (strain EC18) was avirulent. Comparative genomic analyses with virulent ST127
      strains revealed an IS1 mediated deletion in the O-antigen cluster in strain
      EC18, which is likely to explain the lack of virulence in the larvae infection
      model. Virulence in the larvae was not correlated with serotype or phylogenetic
      group. This study illustrates that G. mellonella are an excellent tool for
      investigation of the virulence of UPEC strains. The findings also support our
      suggestion that the incidence of ST127 strains should be monitored, as these
      isolates have not yet been widely reported, but they clearly have a pathogenic
      potential greater than that of more widely recognised clones, including ST73,
      ST95 or ST131.

PMID- 25061820
TI  - The associations of objectively measured physical activity and sedentary time
      with cognitive functions in school-aged children.
AB  - Low levels of physical activity among children have raised concerns over the
      effects of a physically inactive lifestyle, not only on physical health but also
      on cognitive prerequisites of learning. This study examined how objectively
      measured and self-reported physical activity and sedentary behavior are
      associated with cognitive functions in school-aged children. The study population
      consisted of 224 children from five schools in the Jyvaskyla school district in
      Finland (mean age 12.2 years; 56% girls), who participated in the study in the
      spring of 2011. Physical activity and sedentary time were measured objectively
      for seven consecutive days using the ActiGraph GT1M/GT3X accelerometer. Self
      reported moderate to vigorous physical activity (MVPA) and screen time were
      evaluated with the questions used in the "WHO Health Behavior in School-aged
      Children" study. Cognitive functions including visual memory, executive functions
      and attention were evaluated with a computerized Cambridge Neuropsychological
      Test Automated Battery by using five different tests. Structural equation
      modeling was applied to examine how objectively measured and self-reported MVPA
      and sedentary behavior were associated with cognitive functions. High levels of
      objectively measured MVPA were associated with good performance in the reaction
      time test. High levels of objectively measured sedentary time were associated
      with good performance in the sustained attention test. Objectively measured MVPA
      and sedentary time were not associated with other measures of cognitive
      functions. High amount of self-reported computer/video game play was associated
      with weaker performance in working memory test, whereas high amount of computer
      use was associated with weaker performance in test measuring shifting and
      flexibility of attention. Self-reported physical activity and total screen time
      were not associated with any measures of cognitive functions. The results of the
      present study propose that physical activity may benefit attentional processes.
      However, excessive video game play and computer use may have unfavorable
      influence on cognitive functions. 

PMID- 25061822
TI  - Quantitative trait loci for thermal time to flowering and photoperiod
      responsiveness discovered in summer annual-type Brassica napus L.
AB  - Time of flowering is a key adaptive trait in plants and is conditioned by the
      interaction of genes and environmental cues including length of photoperiod,
      ambient temperature and vernalisation. Here we investigated the photoperiod
      responsiveness of summer annual-types of Brassica napus (rapeseed, canola). A
      population of 131 doubled haploid lines derived from a cross between European and
      Australian parents was evaluated for days to flowering, thermal time to flowering
      (measured in degree-days) and the number of leaf nodes at flowering in a compact
      and efficient glasshouse-based experiment with replicated short and long day
      treatments. All three traits were under strong genetic control with heritability
      estimates ranging from 0.85-0.93. There was a very strong photoperiod effect with
      flowering in the population accelerated by 765 degree-days in the long day versus
      short day treatments. However, there was a strong genetic correlation of line
      effects (0.91) between the long and short day treatments and relatively low
      genotype x treatment interaction indicating that photoperiod had a similar effect
      across the population. Bivariate analysis of thermal time to flowering in short
      and long days revealed three main effect quantitative trait loci (QTLs) that
      accounted for 57.7% of the variation in the population and no significant
      interaction QTLs. These results provided insight into the contrasting adaptations
      of Australian and European varieties. Both parents responded to photoperiod and
      their alleles shifted the population to earlier flowering under long days. In
      addition, segregation of QTLs in the population caused wide transgressive
      segregation in thermal time to flowering. Potential candidate flowering time
      homologues located near QTLs were identified with the aid of the Brassica rapa
      reference genome sequence. We discuss how these results will help to guide the
      breeding of summer annual types of B. napus adapted to new and changing
      environments. 

PMID- 25061823
TI  - Measuring stigma among abortion providers: assessing the Abortion Provider Stigma
      Survey instrument.
AB  - We explored the psychometric properties of 15 survey questions that assessed
      abortion providers' perceptions of stigma and its impact on providers'
      professional and personal lives referred to as the Abortion Provider Stigma
      Survey (APSS). We administered the survey to a sample of abortion providers
      recruited for the Providers' Share Workshop (N = 55). We then completed analyses
      using Stata SE/12.0. Exploratory factor analysis, which resulted in 13 retained
      items and identified three subscales: disclosure management, resistance and
      resilience, and discrimination. Stigma was salient in abortion provider's lives:
      they identified difficulties surrounding disclosure (66%) and felt unappreciated
      by society (89%). Simultaneously, workers felt they made a positive contribution
      to society (92%) and took pride in their work (98%). Paired t-test analyses of
      the pre- and post-Workshop APSS scores showed no changes in the total score.
      However, the Disclosure Management subscale scores were significantly lower
      (indicating decreased stigma) for two subgroups of participants: those over the
      age of 30 and those with children. This analysis is a promising first step in the
      development of a quantitative tool for capturing abortion providers' experiences
      of and responses to pervasive abortion stigma.

PMID- 25061824
TI  - Attitudes, Intentions, and Barriers Toward Influenza Vaccination Among Pregnant
      Korean Women.
AB  - Following our study of attitudes, barriers, and intentions concerning the
      influenza vaccination among pregnant women in South Korea, we discovered that
      women displaying a more positive attitude toward the influenza vaccination were
      more likely to receive it during their pregnancy. We also found that attitudes
      toward vaccination were more positive among vaccinated pregnant women than among
      those who were unvaccinated. Furthermore, women showed a greater intention to get
      vaccinated if a clinician, rather than friends, recommended it. The major
      perceived barriers to receiving an influenza vaccination were being pregnant,
      fearing harm to the baby, feeling healthy, and thinking it is unnecessary. 

PMID- 25061825
TI  - Dancing around infertility: the use of metaphors in a complex medical situation.
AB  - People use metaphors to cognitively frame their experiences as well as to explain
      those experiences to others, especially in complex medical situations. However,
      previous research has not fully explored the extent to which metaphors may be
      helpful or harmful to achieving well-being. This investigation fills this gap by
      identifying and explaining metaphor use in the context of infertility. Guided by
      self-determination theory, in-depth interviews were conducted with 22 women and
      men who had experienced an inability to conceive a child. Analysis of participant
      narratives yielded 10 prominent metaphors that reflect how participants' need for
      competence, autonomy, and relatedness were (and were not) met during their
      infertility experience. Results indicate that cognitively framing the infertility
      experience using certain metaphors is more likely to enhance personal and
      relational well-being, while others may be more harmful. Suggestions for
      communication with doctors, partners, families, and friends are discussed. 

PMID- 25061826
TI  - Are they overtreated?

PMID- 25061827
TI  - Response to 'Are they overtreated'.

PMID- 25061828
TI  - Comment on the article 'Flexibility of idiopathic congenital clubfeet treated by
      posteromedial release without talocalcaneal joint release' by Machida et al.

PMID- 25061829
TI  - Response to "Comment on the article 'Flexibility of idiopathic congenital
      clubfeet treated by posteromedial release without talocalcaneal joint release' by
      Machida et al.".

PMID- 25061830
TI  - Automated real-time needle-guide tracking for fast 3-T MR-guided transrectal
      prostate biopsy: a feasibility study.
AB  - PURPOSE: To assess the feasibility of automatic needle-guide tracking by using a
      real-time phase-only cross correlation ( POCC phase-only cross correlation )
      algorithm-based sequence for transrectal 3-T in-bore magnetic resonance (MR)
      guided prostate biopsies. MATERIALS AND METHODS: This study was approved by the
      ethics review board, and written informed consent was obtained from all patients.
      Eleven patients with a prostate-specific antigen level of at least 4 ng/mL (4
      MUg/L) and at least one transrectal ultrasonography-guided biopsy session with
      negative findings were enrolled. Regions suspicious for cancer were identified on
      3-T multiparametric MR images. During a subsequent MR-guided biopsy, the regions
      suspicious for cancer were reidentified and targeted by using the POCC phase-only
      cross correlation -based tracking sequence. Besides testing a general technical
      feasibility of the biopsy procedure by using the POCC phase-only cross
      correlation -based tracking sequence, the procedure times were measured, and a
      pathologic analysis of the biopsy cores was performed. RESULTS: Thirty-eight core
      samples were obtained from 25 regions suspicious for cancer. It was technically
      feasible to perform the POCC phase-only cross correlation -based biopsies in all
      regions suspicious for cancer in each patient, with adequate biopsy samples
      obtained with each biopsy attempt. The median size of the region suspicious for
      cancer was 8 mm (range, 4-13 mm). In each region suspicious for cancer (median
      number per patient, two; range, 1-4), a median of one core sample per region was
      obtained (range, 1-3). The median time for guidance per target was 1.5 minutes
      (range, 0.7-5 minutes). Nineteen of 38 core biopsy samples contained cancer.
      CONCLUSION: This study shows that it is feasible to perform transrectal 3-T MR
      guided biopsies by using a POCC phase-only cross correlation algorithm-based real
      time tracking sequence.

PMID- 25061831
TI  - Multimodal approach to detect osseous involvement in meningioma: additional value
      of (18)F-fluoride PET/CT for conventional imaging.
AB  - PURPOSE: To compare the diagnostic performance of fluorine 18 ((18)F) fluoride
      positron emission tomography (PET)/computed tomography (CT) with that of
      conventional imaging (CT and magnetic resonance [MR] imaging) in evaluating the
      osseous involvement in meningioma. MATERIALS AND METHODS: The study was approved
      by the ethics committee and institutional review board and was conducted
      according to the Declarations of Helsinki and Tokyo. Written informed consent was
      obtained from all patients. A retrospective comparative study between (18)F
      fluoride PET/CT and conventional imaging was conducted to detect osseous
      involvement in patients with a verified diagnosis of meningioma. Osseous
      involvement was verified by using definitive surgery (including drilling or
      careful sampling of the skull in all patients). The diagnostic performance,
      determined by calculating the sensitivity, specificity, positive predictive value
      ( PPV positive predictive value ), negative predictive value ( NPV negative
      predictive value ), and accuracy, was assessed. RESULTS: Data sets from a total
      of 78 patients with proven meningioma were compared. Osseous involvement was
      histopathologically confirmed in 25 patients (32%). The sensitivity, specificity,
      PPV positive predictive value , NPV negative predictive value , and accuracy were
      92.0%, 86.8%, 76.7%, 95.8%, and 88.5% for (18)F-fluoride PET/CT and 64.0%, 83.0%,
      64.0%, 83.0%, and 76.9% for conventional imaging, respectively. The receiver
      operating characteristic ( ROC receiver operating characteristic ) analysis
      revealed that the area under the ROC receiver operating characteristic curve ( Az
      area under the ROC curve ) value of (18)F-fluoride PET/CT was significantly
      greater than that of conventional imaging (0.965 +/- 0.02 [standard error] vs
      0.703 +/- 0.066 [standard error], P < .0001). CONCLUSION: An approach using (18)F
      fluoride PET/CT improves preoperative detection of osseous involvement. In those
      without abnormal (18)F-fluoride uptake within the skull, the patient may proceed
      directly to conventional surgery. However, a positive finding of osseous
      involvement at (18)F-fluoride PET/CT should prompt confirmation by drilling or
      sampling of bone.

PMID- 25061832
TI  - Movement of chikungunya virus into the Western hemisphere.

PMID- 25061833
TI  - Conversion, correction, and International Scale standardization: results From a
      Multicenter External Quality Assessment Study for BCR-ABL1 testing.
AB  - CONTEXT: Monitoring BCR-ABL1 expression levels relative to clinically validated
      response criteria on the International Scale (IS) is vital in the optimal
      management of patients with chronic myeloid leukemia, yet significant variability
      remains across laboratories worldwide. OBJECTIVE: To assess method performance,
      interlaboratory precision, and different IS standardization modalities in
      representative laboratories performing routine BCR-ABL1 testing. DESIGN: Fifteen
      blinded test specimens with 5-level nominal BCR-ABL1 to ABL1 IS percentage ratios
      ranging from 5% to 0.0005% and 4-level secondary IS reference panels, the ARQ IS
      Calibrator Panels, were tested by relative quantitative polymerase chain reaction
      in 15 laboratories in 5 countries. Both raw and IS percentage ratios calculated
      by using local conversion factors (CFs) or analytic correction parameters (CPs)
      were collected and analyzed. RESULTS: A total of 670 valid positive results were
      generated. BCR-ABL1 detection was associated with variable ABL1 quality metric
      passing rates (P < .001) and reached at least 0.01% in 13 laboratories.
      Intralaboratory precision was within 2.5-fold for all sample levels combined with
      a relative mean difference greater than 5-fold across laboratories. International
      Scale accuracy was increased by using both the CF and CP standardization methods.
      Classification agreement for major molecular response status was 90% after CF
      conversion and 93% after CP correction, with precision improved by 3-fold for the
      CP method. CONCLUSIONS: Despite preanalytic and analytic differences between
      laboratories, conversion and correction are effective IS standardization methods.
      Validated secondary reference materials can facilitate global diffusion of the IS
      without the need to perform sample exchange and improve the accuracy and
      precision of BCR-ABL1 quantitative measurements, including at low levels of
      residual disease.

PMID- 25061834
TI  - Temperature measurement in PV facilities on a per-panel scale.
AB  - This paper presents the design, construction and testing of an instrumentation
      system for temperature measurement in PV facilities on a per-panel scale (i.e.,
      one or more temperature measurements per panel). Its main characteristics are:
      precision, ease of connection, immunity to noise, remote operation, easy scaling;
      and all of this at a very low cost. The paper discusses the advantages of
      temperature measurements in PV facilities on a per-panel scale. The paper
      presents the whole development to implementation of a real system that is being
      tested in an actual facility. This has enabled the authors to provide the readers
      with practical guidelines, which would be very difficult to achieve if the
      developments were implemented by just simulation or in a theoretical way. The
      instrumentation system is fully developed, from the temperature sensing to its
      presentation in a virtual instrument. The developed instrumentation system is
      able to work both locally and remotely connected to both wired and wireless
      network. 

PMID- 25061835
TI  - A sensor fusion method for tracking vertical velocity and height based on
      inertial and barometric altimeter measurements.
AB  - A sensor fusion method was developed for vertical channel stabilization by fusing
      inertial measurements from an Inertial Measurement Unit (IMU) and pressure
      altitude measurements from a barometric altimeter integrated in the same device
      (baro-IMU). An Extended Kalman Filter (EKF) estimated the quaternion from the
      sensor frame to the navigation frame; the sensed specific force was rotated into
      the navigation frame and compensated for gravity, yielding the vertical linear
      acceleration; finally, a complementary filter driven by the vertical linear
      acceleration and the measured pressure altitude produced estimates of height and
      vertical velocity. A method was also developed to condition the measured pressure
      altitude using a whitening filter, which helped to remove the short-term
      correlation due to environment-dependent pressure changes from raw pressure
      altitude. The sensor fusion method was implemented to work on-line using data
      from a wireless baro-IMU and tested for the capability of tracking low-frequency
      small-amplitude vertical human-like motions that can be critical for stand-alone
      inertial sensor measurements. Validation tests were performed in different
      experimental conditions, namely no motion, free-fall motion, forced circular
      motion and squatting. Accurate on-line tracking of height and vertical velocity
      was achieved, giving confidence to the use of the sensor fusion method for
      tracking typical vertical human motions: velocity Root Mean Square Error (RMSE)
      was in the range 0.04-0.24 m/s; height RMSE was in the range 5-68 cm, with
      statistically significant performance gains when the whitening filter was used by
      the sensor fusion method to track relatively high-frequency vertical motions. 

PMID- 25061836
TI  - A digital multigate Doppler method for high frequency ultrasound.
AB  - Noninvasive visualization of blood flow with high frequency Doppler ultrasound
      has been extensively used to assess the morphology and hemodynamics of the
      microcirculation. A completely digital implementation of multigate pulsed-wave
      (PW) Doppler method was proposed in this paper for high frequency ultrasound
      applications. Analog mixer was eliminated by a digital demodulator and the same
      data acquisition path was shared with traditional B-mode imaging which made the
      design compact and flexible. Hilbert transform based quadrature demodulation
      scheme was employed to achieve the multigate Doppler acquisition. A programmable
      high frequency ultrasound platform was also proposed to facilitate the multigate
      flow visualization. Experimental results showed good performance of the proposed
      method. Parabolic velocity gradient inside the vessel and velocity profile with
      different time slots were acquired to demonstrate the functionality of the
      multigate Doppler. Slow wall motion was also recorded by the proposed method. 

PMID- 25061837
TI  - Emotion recognition from single-trial EEG based on kernel Fisher's emotion
      pattern and imbalanced quasiconformal kernel support vector machine.
AB  - Electroencephalogram-based emotion recognition (EEG-ER) has received increasing
      attention in the fields of health care, affective computing, and brain-computer
      interface (BCI). However, satisfactory ER performance within a bi-dimensional and
      non-discrete emotional space using single-trial EEG data remains a challenging
      task. To address this issue, we propose a three-layer scheme for single-trial EEG
      ER. In the first layer, a set of spectral powers of different EEG frequency bands
      are extracted from multi-channel single-trial EEG signals. In the second layer,
      the kernel Fisher's discriminant analysis method is applied to further extract
      features with better discrimination ability from the EEG spectral powers. The
      feature vector produced by layer 2 is called a kernel Fisher's emotion pattern
      (KFEP), and is sent into layer 3 for further classification where the proposed
      imbalanced quasiconformal kernel support vector machine (IQK-SVM) serves as the
      emotion classifier. The outputs of the three layer EEG-ER system include labels
      of emotional valence and arousal. Furthermore, to collect effective training and
      testing datasets for the current EEG-ER system, we also use an emotion-induction
      paradigm in which a set of pictures selected from the International Affective
      Picture System (IAPS) are employed as emotion induction stimuli. The performance
      of the proposed three-layer solution is compared with that of other EEG spectral
      power-based features and emotion classifiers. Results on 10 healthy participants
      indicate that the proposed KFEP feature performs better than other spectral power
      features, and IQK-SVM outperforms traditional SVM in terms of the EEG-ER
      accuracy. Our findings also show that the proposed EEG-ER scheme achieves the
      highest classification accuracies of valence (82.68%) and arousal (84.79%) among
      all testing methods. 

PMID- 25061838
TI  - MobiPag: integrated mobile payment, ticketing and couponing solution based on
      NFC.
AB  - Mobile payments still remain essentially an emerging technology, seeking to fill
      the gap between the envisioned potential and widespread usage. In this paper, we
      present an integrated mobile service solution based on the near field
      communication (NFC) protocol that was developed under a research project called
      MobiPag. The most distinctive characteristic of Mobipag is its open architectural
      model that allows multiple partners to become part of the payment value-chain and
      create solutions that complement payments in many unexpected ways. We describe
      the Mobipag architecture and how it has been used to support a mobile payment
      trial. We identify a set of design lessons resulting from usage experiences
      associated with real-world payment situations with NFC-enabled mobile phones.
      Based on results from this trial, we identify a number of challenges and
      guidelines that may help to shape future versions of NFC-based payment systems.
      In particular, we highlight key challenges for the initial phases of payment
      deployments, where it is essential to focus on scenarios that can be identified
      as more feasible for early adoption. We also have identified a fundamental trade
      off between the flexibility supported by the Mobipag solution and the respective
      implications for the payment process, particularly on the users' mental model. 

PMID- 25061839
TI  - Experimental energy consumption of Frame Slotted ALOHA and Distributed Queuing
      for data collection scenarios.
AB  - Data collection is a key scenario for the Internet of Things because it enables
      gathering sensor data from distributed nodes that use low-power and long-range
      wireless technologies to communicate in a single-hop approach. In this kind of
      scenario, the network is composed of one coordinator that covers a particular
      area and a large number of nodes, typically hundreds or thousands, that transmit
      data to the coordinator upon request. Considering this scenario, in this paper we
      experimentally validate the energy consumption of two Medium Access Control (MAC)
      protocols, Frame Slotted ALOHA (FSA) and Distributed Queuing (DQ). We model both
      protocols as a state machine and conduct experiments to measure the average
      energy consumption in each state and the average number of times that a node has
      to be in each state in order to transmit a data packet to the coordinator. The
      results show that FSA is more energy efficient than DQ if the number of nodes is
      known a priori because the number of slots per frame can be adjusted accordingly.
      However, in such scenarios the number of nodes cannot be easily anticipated,
      leading to additional packet collisions and a higher energy consumption due to
      retransmissions. Contrarily, DQ does not require to know the number of nodes in
      advance because it is able to efficiently construct an ad hoc network schedule
      for each collection round. This kind of a schedule ensures that there are no
      packet collisions during data transmission, thus leading to an energy consumption
      reduction above 10% compared to FSA. 

PMID- 25061840
TI  - Trends in correlation-based pattern recognition and tracking in forward-looking
      infrared imagery.
AB  - In this paper, we review the recent trends and advancements on correlation-based
      pattern recognition and tracking in forward-looking infrared (FLIR) imagery. In
      particular, we discuss matched filter-based correlation techniques for target
      detection and tracking which are widely used for various real time applications.
      We analyze and present test results involving recently reported matched filters
      such as the maximum average correlation height (MACH) filter and its variants,
      and distance classifier correlation filter (DCCF) and its variants. Test results
      are presented for both single/multiple target detection and tracking using
      various real-life FLIR image sequences. 

PMID- 25061841
TI  - From the solution processing of hydrophilic molecules to polymer-phthalocyanine
      hybrid materials for ammonia sensing in high humidity atmospheres.
AB  - We have prepared different hybrid polymer-phthalocyanine materials by solution
      processing, starting from two sulfonated phthalocyanines, s-CoPc and CuTsPc, and
      polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), poly(acrylic acid-co
      acrylamide) (PAA-AM), poly(diallyldimethylammonium chloride) (PDDA) and
      polyaniline (PANI) as polymers. We also studied the response to ammonia (NH3) of
      resistors prepared from these sensing materials. The solvent casted films,
      prepared from s-CoPc and PVP, PEG and PAA-AM, were highly insulating and very
      sensitive to the relative humidity (RH) variation. The incorporation of s-CoPc in
      PDDA by means of layer-by-layer (LBL) technique allowed to stabilize the film,
      but was too insulating to be interesting. We also prepared PANI-CuTsPc hybrid
      films by LBL technique. It allowed a regular deposition as evidenced by the
      linear increase of the absorbance at 688 nm as a function of the number of
      bilayers. The sensitivity to ammonia (NH3) of PANi-CuTsPc resistors was very high
      compared to that of individual materials, giving up to 80% of current decrease
      when exposed to 30 ppm NH3. Contrarily to what happens with neutral polymers, in
      PANI, CuTsPc was stabilized by strong electrostatic interactions, leading to a
      stable response to NH3, whatever the relative humidity in the range 10%-70%.
      Thus, the synergy of PANI with ionic macrocycles used as counteranions combined
      with their simple aqueous solution processing opens the way to the development of
      new gas sensors capable of operating in real world conditions. 

PMID- 25061842
TI  - Serologic surveillance for West Nile virus in dogs, Africa.

PMID- 25061843
TI  - Quantifying inter-laboratory variability in stable isotope analysis of ancient
      skeletal remains.
AB  - Over the past forty years, stable isotope analysis of bone (and tooth) collagen
      and hydroxyapatite has become a mainstay of archaeological and
      paleoanthropological reconstructions of paleodiet and paleoenvironment. Despite
      this method's frequent use across anthropological subdisciplines (and beyond),
      the present work represents the first attempt at gauging the effects of inter
      laboratory variability engendered by differences in a) sample preparation, and b)
      analysis (instrumentation, working standards, and data calibration). Replicate
      analyses of a 14C-dated ancient human bone by twenty-one archaeological and
      paleoecological stable isotope laboratories revealed significant inter-laboratory
      isotopic variation for both collagen and carbonate. For bone collagen, we found a
      sizeable range of 1.80/00 for delta13Ccol and 1.90/00 for delta15Ncol among
      laboratories, but an interpretatively insignificant average pairwise difference
      of 0.20/00 and 0.40/00 for delta13Ccol and delta15Ncol respectively. For bone
      hydroxyapatite the observed range increased to a troublingly large 3.50/00 for
      delta13Cap and 6.70/00 for delta18Oap, with average pairwise differences of
      0.60/00 for delta13Cap and a disquieting 2.00/00 for delta18Oap. In order to
      assess the effects of preparation versus analysis on isotopic variability among
      laboratories, a subset of the samples prepared by the participating laboratories
      were analyzed a second time on the same instrument. Based on this duplicate
      analysis, it was determined that roughly half of the isotopic variability among
      laboratories could be attributed to differences in sample preparation, with the
      other half resulting from differences in analysis (instrumentation, working
      standards, and data calibration). These findings have serious implications for
      choices made in the preparation and extraction of target biomolecules, the
      comparison of results obtained from different laboratories, and the
      interpretation of small differences in bone collagen and hydroxyapatite isotope
      values. To address the issues arising from inter-laboratory comparisons, we
      devise a novel measure we term the Minimum Meaningful Difference (MMD), and
      demonstrate its application. 

PMID- 25061844
TI  - Systematic evaluation and optimization of modification reactions of
      oligonucleotides with amines and carboxylic acids for the synthesis of DNA
      encoded chemical libraries.
AB  - DNA-encoded chemical libraries are collections of small molecules, attached to
      DNA fragments serving as identification barcodes, which can be screened against
      multiple protein targets, thus facilitating the drug discovery process. The
      preparation of large DNA-encoded chemical libraries crucially depends on the
      availability of robust synthetic methods, which enable the efficient conjugation
      to oligonucleotides of structurally diverse building blocks, sharing a common
      reactive group. Reactions of DNA derivatives with amines and/or carboxylic acids
      are particularly attractive for the synthesis of encoded libraries, in view of
      the very large number of building blocks that are commercially available.
      However, systematic studies on these reactions in the presence of DNA have not
      been reported so far. We first investigated conditions for the coupling of
      primary amines to oligonucleotides, using either a nucleophilic attack on
      chloroacetamide derivatives or a reductive amination on aldehyde-modified DNA.
      While both methods could be used for the production of secondary amines, the
      reductive amination approach was generally associated with higher yields and
      better purity. In a second endeavor, we optimized conditions for the coupling of
      a diverse set of 501 carboxylic acids to DNA derivatives, carrying primary and
      secondary amine functions. The coupling efficiency was generally higher for
      primary amines, compared to secondary amine substituents, but varied considerably
      depending on the structure of the acids and on the synthetic methods used.
      Optimal reaction conditions could be found for certain sets of compounds (with
      conversions >80%), but multiple reaction schemes are needed when assembling large
      libraries with highly diverse building blocks. The reactions and experimental
      conditions presented in this article should facilitate the synthesis of future
      DNA-encoded chemical libraries, while outlining the synthetic challenges that
      remain to be overcome. 

PMID- 25061845
TI  - Intramolecular dehydro-Diels-Alder reaction affords selective entry to
      arylnaphthalene or aryldihydronaphthalene lignans.
AB  - Intramolecular dehydro-Diels-Alder (DDA) reactions are performed affording
      arylnaphthalene or aryldihydronaphthalene lactones selectively as determined by
      choice of reaction solvent. This constitutes the first report of an entirely
      selective formation of arylnaphthalene lactones utilizing DDA reactions of
      styrene-ynes. The synthetic utility of the DDA reaction is demonstrated by the
      synthesis of taiwanin C, retrohelioxanthin, justicidin B, isojusticidin B, and
      their dihydronaphthalene derivatives. Computational methods for chemical shift
      assignment are presented that allow for regioisomeric lignans to be
      distinguished. 

PMID- 25061846
TI  - Kinetics of pressure induced structural changes in super- or near-critical CO2
      microemulsions.
AB  - CO2-microemulsions show strong pressure dependent properties. Using time-resolved
      SANS to investigate the kinetics of structural changes upon periodic pressure
      jumps of adjustable amplitude, we found that the compression-induced formation of
      cylinders occurs on a timescale of one second, whereas the expansion-induced
      disintegration into CO2 swollen spherical micelles is much faster. 

PMID- 25061848
TI  - Biocolloids based on amphiphilic block copolymers as a medium for enzyme
      encapsulation.
AB  - The ability of two biocompatible amphiphilic block copolymers consisting of
      hydrophilic poly(ethylene oxide) and hydrophobic poly(epsilon-caprolactone) with
      different hydrophilic/hydrophobic block ratio to act as stabilizers of water-in
      oil (w/o) microemulsions and enzyme encapsulation therein has been tested. Phase
      diagrams of the two block copolymers in mixtures of chloroform/isopropanol/water
      were constructed, revealing that the systems can incorporate important amounts of
      aqueous phase. The w/o microemulsions were then used to encapsulate R. miehei
      lipase. Empty as well as lipase-loaded systems were characterized by DLS as well
      as EPR spectroscopy. It was found that the incorporated lipase was preferably
      localized in the interior of the droplets. The apparent hydrodynamic radii of the
      droplets were found to vary from 86 to 3000 nm and from 66 to 2140 nm for empty
      PEO-PCL 30 and PEO-PCL 53 stabilized systems, respectively. In the presence of
      the lipase, the hydrodynamic radii were considerably decreased. The catalytic
      activity of the encapsulated lipase was successfully tested via a model
      esterification reaction. The effect of temperature on the catalytic behavior of
      the encapsulated R. miehei lipase was investigated, revealing that the initial
      rate of the esterification reaction depended on the type of the block copolymer
      used. 

PMID- 25061847
TI  - Developmental programming: prenatal steroid excess disrupts key members of
      intraovarian steroidogenic pathway in sheep.
AB  - Prenatal testosterone (T) excess disrupts ovarian cyclicity and increases
      circulating estradiol levels as well as follicular recruitment and persistence
      culminating in multifollicular ovary similar to women with polycystic ovary
      syndrome. We tested whether prenatal T excess, by androgenic or estrogenic
      action, disrupts the steroid biosynthetic machinery in sheep in a cell-, follicle
      stage-, age-, and treatment-specific manner consistent with the ovarian
      disruptions and increased estradiol release. Impact of T/dihydrotestosterone
      (DHT) treatments from days 30-90 of gestation on steroidogenic acute regulatory
      protein, 3beta-hydroxysteroid dehydrogenase, cytochrome P-450 17alpha
      hydroxylase/C17, 20-lyase (CYP17A1), and cytochrome P-450 aromatase (CYP19A1)
      were examined on fetal day 90, 140 and 10 months (postpubertal), and 21 months
      (adult, no DHT group) of age by immunohistochemistry. All 4 markers changed in a
      cell-, follicle stage-, and age-specific manner. Both treatments increased
      steroidogenic acute regulatory protein expression in preantral follicles of
      postpubertal and adult females. Effects of prenatal T and DHT on 3beta
      hydroxysteroid dehydrogenase differed in a follicle- and age-specific manner.
      CYP17A1 was reduced in the theca interna of antral follicles by T, but not DHT,
      in 10- and 21-month-old females. CYP19A1 was reduced by both T and DHT at all
      ages barring an increase on fetal day 140. Reduced granulosa CYP19A1 and thecal
      CYP17A1 in adults likely disrupt the intrafollicular androgen/estrogen balance
      contributing to follicular persistence. The reduced thecal CYP17A1 expression
      suggests that the hyperandrogenic ovarian phenotype may originate from increased
      enzyme activity or alternatively via a different isoform of CYP17. The reduced
      CYP19A1 in antral follicles of adults indicates that the increased circulating
      estradiol release likely arises from the increased number of persisting
      follicles. 

PMID- 25061849
TI  - Activatable fluorescence/MRI bimodal platform for tumor cell imaging via MnO2
      nanosheet-aptamer nanoprobe.
AB  - A novel dual-activatable fluorescence/MRI bimodal platform is designed for tumor
      cell imaging by using a redoxable manganese dioxide (MnO2) nanosheet-aptamer
      nanoprobe. The redoxable MnO2 nanosheet acts as a DNA nanocarrier, fluorescence
      quencher, and intracellular glutathione (GSH)-activated MRI contrast agent. In
      the absence of target cells, neither fluorescence signaling nor MRI contrast of
      the nanoprobe is activated. In the presence of target cells, the binding of
      aptamers to their targets weakens the adsorption of aptamers on the MnO2
      nanosheets, causing partial fluorescence recovery, illuminating the target cells,
      and also facilitating the endocytosis of nanoprobes into target cells. After
      endocytosis, the reduction of MnO2 nanosheets by GSH further activates the
      fluorescence signals and generates large amounts of Mn(2+) ions suitable for MRI.
      This platform should facilitate the development of various dual-activatable
      fluorescence/MRI bimodalities for use in cells or in vivo. 

PMID- 25061852
TI  - Density functional theory versus complete active space self-consistent field
      investigation of the half-metallic character of graphite-like and amorphous
      carbon nanoparticles.
AB  - Model carbon nanoparticles representative of the graphite-like and amorphous
      domains of active carbon are investigated with density functional theory (DFT)
      and complete active space self-consistent field (CASSCF) methods. Cyclic carbon
      clusters containing conjugated carbene groups are found to undergo Jahn-Teller
      distortion. More importantly, the half-metallicity, that is, the equal or similar
      stability of various spin states, previously suggested by DFT calculations for
      both types of nanosized clusters is confirmed by CASSCF calculations.
      Furthermore, the model carbon clusters are found to possess a
      multiconfigurational electronic structure dominated by high-spin configurations.
      When compared to CASSCF results, the single-reference DFT predicts proper
      electronic structures, characterized by antiferromagnetically coupled electron
      pairs, at the expense of spin contamination as a reflection of the
      multiconfigurational character. In fact, spin contamination, which is normally
      viewed as an error, does not corrupt the energetics of the half-metallic systems
      and therefore does not preclude the applicability of DFT to such systems. 

PMID- 25061850
TI  - Transformation of human cathelicidin LL-37 into selective, stable, and potent
      antimicrobial compounds.
AB  - This Letter reports a family of novel antimicrobial compounds obtained by
      combining peptide library screening with structure-based design. Library
      screening led to the identification of a human LL-37 peptide resistant to
      chymotrypsin. This d-amino-acid-containing peptide template was active against
      Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It
      possesses a unique nonclassic amphipathic structure with hydrophobic defects. By
      repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against
      the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella
      pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter
      species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In
      vivo, the peptide prevented staphylococcal biofilm formation in a mouse model of
      catheter-associated infection. Meanwhile, it boosted the innate immune response
      to further combat the infection. Because these peptides are potent, cell
      selective, and stable to several proteases, they may be utilized to combat one or
      more ESKAPE pathogens. 

PMID- 25061851
TI  - Severe fever with thrombocytopenia syndrome virus in ticks collected from humans,
      South Korea, 2013.
AB  - We investigated the infection rate for severe fever with thrombocytopenia
      syndrome virus (SFTSV) among ticks collected from humans during May-October 2013
      in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV
      vector. However, we detected the virus in H. longicornis, Amblyomma
      testudinarium, and Ixodes nipponensis ticks, indicating additional potential
      SFTSV vectors. 

PMID- 25061853
TI  - Sika deer carrying Babesia parasites closely related to B. divergens, Japan.

PMID- 25061854
TI  - What's new in the topical treatment of allergic skin diseases.
AB  - PURPOSE OF REVIEW: To review recent literature on the topical treatment of
      allergic skin diseases to help clinicians make informed evidence-based decisions.
      RECENT FINDINGS: Twenty-four publications were identified from a PubMed search of
      randomized controlled trials and systematic reviews of topical treatment of
      atopic dermatitis and allergic contact dermatitis published from 1 January 2013
      to 31 January 2014. Studies on the topical treatment of atopic dermatitis largely
      supported the recommended use of topical corticosteroids and topical calcineurin
      inhibitors. Barrier therapy continues to play an important role without evidence
      supporting use of one emollient over another. Lipoxin A4, an eicosanoid with anti
      inflammatory properties, and a 5% cis-urocanic acid emulsion cream were effective
      in the treatment of atopic dermatitis, although studies were small. Adjunct
      therapy with bleach baths, natural oils, and textiles all showed some benefit;
      however, studies are limited. Literature on topical treatment of allergic contact
      dermatitis was limited to one publication, providing evidence for a natural
      multicomponent cream as maintenance therapy after control of disease with a
      topical corticosteroid. SUMMARY: There is strong evidence for the use of topical
      anti-inflammatory therapies in the treatment of atopic dermatitis. There is
      little evidence to suggest that one emollient is better than others.

PMID- 25061856
TI  - Ruled by ubiquitylation: a new order for polycomb recruitment.
AB  - Polycomb complexes are found in most cells, but they must be targeted to specific
      genes in specific cell types in order to regulate pluripotency and
      differentiation. The recruitment of Polycomb complexes to specific targets has
      been widely thought to occur in two steps: first, one complex, PRC2, produces
      histone H3 lysine 27 (H3K27) trimethylation at a specific gene, and then the PRC1
      complex is recruited by its ability to bind to H3K27me3. Now, three new articles
      turn this model upside-down by showing that binding of a variant PRC1 complex and
      subsequent H2A ubiquitylation of surrounding chromatin is sufficient to trigger
      the recruitment of PRC2 and H3K27 trimethylation. These studies also show that
      ubiquitylated H2A is directly sensed by PRC2 and that ablation of PRC1-mediated
      H2A ubiquitylation impairs genome-wide PRC2 binding and disrupts mouse
      development. 

PMID- 25061855
TI  - Conjunctival epithelial and goblet cell function in chronic inflammation and
      ocular allergic inflammation.
AB  - PURPOSE OF REVIEW: Although conjunctival goblet cells are a major cell type in
      ocular mucosa, their responses during ocular allergy are largely unexplored. This
      review summarizes the recent findings that provide key insights into the
      mechanisms by which their function and survival are altered during chronic
      inflammatory responses, including ocular allergy. RECENT FINDINGS: Conjunctiva
      represents a major component of the ocular mucosa that harbors specialized
      lymphoid tissue. Exposure of mucin-secreting goblet cells to allergic and
      inflammatory mediators released by the local innate and adaptive immune cells
      modulates proliferation, secretory function, and cell survival. Allergic
      mediators like histamine, leukotrienes, and prostaglandins directly stimulate
      goblet cell mucin secretion and consistently increase goblet cell proliferation.
      Goblet cell mucin secretion is also detectable in a murine model of allergic
      conjunctivitis. Additionally, primary goblet cell cultures allow evaluation of
      various inflammatory cytokines with respect to changes in goblet cell mucin
      secretion, proliferation, and apoptosis. These findings in combination with the
      preclinical mouse models help understand the goblet cell responses and their
      modulation during chronic inflammatory diseases, including ocular allergy.
      SUMMARY: Recent findings related to conjunctival goblet cells provide the basis
      for novel therapeutic approaches, involving modulation of goblet cell mucin
      production, to improve treatment of ocular allergies.

PMID- 25061857
TI  - Full-length recombinant human SCF1-165 is more thermostable than the truncated
      SCF1-141 form.
AB  - Human stem cell factor initiates a diverse array of cellular responses, including
      hematopoiesis, cell proliferation, differentiation, migration and survival. To
      explore the relationship between its structure and function, we produced
      recombinant soluble human stem cell factor1-165 (wild type) and human stem cell
      factor1-141 (C-terminal truncated) in a yeast expression system and compared
      their biological activities and thermal stabilities. The biological activity of
      the two proteins was measured as a function of TF-1 cell viability and effects on
      downstream signaling targets after incubation. We found that these proteins
      enhanced cell viability and downstream signaling to a similar extent, in a dose
      dependent manner. The biological activity of recombinant human stem cell factor1
      165 was significantly greater than that of recombinant human stem cell factor1
      141 after heating the proteins (100 ng/mL) at 25-110 degrees C for 10 minutes
      (P<0.05 for all temperatures). In addition, circular dichroism spectral analysis
      indicated that beta-sheet structures were altered in recombinant human stem cell
      factor1-141 but not recombinant human stem cell factor1-165 after heating at 90
      degrees C for 15 or 30 min. Molecular modeling and limited proteolytic digestion
      were also used to compare the thermo stability between human stem cell factor1
      165 and human stem cell factor1-141. Together, these data indicate that stem cell
      factor1-165 is more thermostable than stem cell factor1-141. 

PMID- 25061858
TI  - Documenting biogeographical patterns of African timber species using herbarium
      records: a conservation perspective based on native trees from Angola.
AB  - In many tropical regions the development of informed conservation strategies is
      hindered by a dearth of biodiversity information. Biological collections can help
      to overcome this problem, by providing baseline information to guide research and
      conservation efforts. This study focuses on the timber trees of Angola, combining
      herbarium (2670 records) and bibliographic data to identify the main timber
      species, document biogeographic patterns and identify conservation priorities.
      The study recognized 18 key species, most of which are threatened or near
      threatened globally, or lack formal conservation assessments. Biogeographical
      analysis reveals three groups of species associated with the enclave of Cabinda
      and northwest Angola, which occur primarily in Guineo-Congolian rainforests, and
      evergreen forests and woodlands. The fourth group is widespread across the
      country, and is mostly associated with dry forests. There is little
      correspondence between the spatial pattern of species groups and the ecoregions
      adopted by WWF, suggesting that these may not provide an adequate basis for
      conservation planning for Angolan timber trees. Eight of the species evaluated
      should be given high conservation priority since they are of global conservation
      concern, they have very restricted distributions in Angola, their historical
      collection localities are largely outside protected areas and they may be under
      increasing logging pressure. High conservation priority was also attributed to
      another three species that have a large proportion of their global range
      concentrated in Angola and that occur in dry forests where deforestation rates
      are high. Our results suggest that timber tree species in Angola may be under
      increasing risk, thus calling for efforts to promote their conservation and
      sustainable exploitation. The study also highlights the importance of studying
      historic herbarium collections in poorly explored regions of the tropics, though
      new field surveys remain a priority to update historical information. 

PMID- 25061859
TI  - Slik and the receptor tyrosine kinase Breathless mediate localized activation of
      Moesin in terminal tracheal cells.
AB  - A key element in the regulation of subcellular branching and tube morphogenesis
      of the Drosophila tracheal system is the organization of the actin cytoskeleton
      by the ERM protein Moesin. Activation of Moesin within specific subdomains of
      cells, critical for its interaction with actin, is a tightly controlled process
      and involves regulatory inputs from membrane proteins, kinases and phosphatases.
      The kinases that activate Moesin in tracheal cells are not known. Here we show
      that the Sterile-20 like kinase Slik, enriched at the luminal membrane, is
      necessary for the activation of Moesin at the luminal membrane and regulates
      branching and subcellular tube morphogenesis of terminal cells. Our results
      reveal the FGF-receptor Breathless as an additional necessary cue for the
      activation of Moesin in terminal cells. Breathless-mediated activation of Moesin
      is independent of the canonical MAP kinase pathway. 

PMID- 25061862
TI  - Correlation of diffusion tensor tractography and intraoperative macrostimulation
      during deep brain stimulation for Parkinson disease.
AB  - OBJECTIVES: The purpose of this study was to investigate whether diffusion tensor
      imaging (DTI) of the corticospinal tract (CST) is a reliable surrogate for
      intraoperative macrostimulation through the deep brain stimulation (DBS) leads.
      The authors hypothesized that the distance on MRI from the DBS lead to the CST as
      determined by DTI would correlate with intraoperative motor thresholds from
      macrostimulations through the same DBS lead. METHODS: The authors retrospectively
      reviewed pre- and postoperative MRI studies and intraoperative macrostimulation
      recordings in 17 patients with Parkinson disease (PD) treated by DBS stimulation.
      Preoperative DTI tractography of the CST was coregistered with postoperative MRI
      studies showing the position of the DBS leads. The shortest distance and the
      angle from each contact of each DBS lead to the CST was automatically calculated
      using software-based analysis. The distance measurements calculated for each
      contact were evaluated with respect to the intraoperative voltage thresholds that
      elicited a motor response at each contact. RESULTS: There was a nonsignificant
      trend for voltage thresholds to increase when the distances between the DBS leads
      and the CST increased. There was a significant correlation between the angle and
      the voltage, but the correlation was weak (coefficient of correlation [R] =
      0.36). CONCLUSIONS: Caution needs to be exercised when using DTI tractography
      information to guide DBS lead placement in patients with PD. Further studies are
      needed to compare DTI tractography measurements with other approaches such as
      microelectrode recordings and conventional intraoperative MRI-guided placement of
      DBS leads.

PMID- 25061861
TI  - Intoxication of host cells by the T3SS phospholipase ExoU: PI(4,5)P2-associated,
      cytoskeletal collapse and late phase membrane blebbing.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that is associated with
      hospital-acquired infections, ventilator-associated pneumonia, and morbidity of
      immunocompromised individuals. A subpopulation of P. aeruginosa encodes a
      protein, ExoU, which exhibits acute cytotoxicity. Toxicity is directly related to
      the phospholipase A2 activity of the protein after injection into the host
      cytoplasm via a type III secretion system. ExoU enzymatic activity requires
      eukaryotic cofactors, ubiquitin or ubiquitin-modified proteins. When administered
      extracellularly, ExoU is unable to intoxicate epithelial cells in culture, even
      in the presence of the cofactor. Injection or transfection of ExoU is necessary
      to observe the acute cytotoxic response. Biochemical approaches indicate that
      ExoU possesses high affinity to a multifunctional phosphoinositide,
      phosphatidylinositol 4,5-bisphosphate or PI(4,5)P2 and that it is capable of
      utilizing this phospholipid as a substrate. In eukaryotic cells, PI(4,5)P2 is
      mainly located in the cytoplasmic side of the plasma membrane and anchors adaptor
      proteins that are involved in cytoskeletal structures, focal adhesions, and
      plasma membranes. Time-lapse fluorescent microscopy analyses of infected live
      cells demonstrate that ExoU intoxication correlates with intracellular damage in
      the early phases of infection, such as disruption of focal adhesions,
      cytoskeletal collapse, actin depolymerization, and cell rounding. At later time
      points, a membrane blebbing phenotype was prominent prior to the loss of the
      plasma membrane integrity and barrier function. Membrane blebbing appears to
      accelerate membrane rupture and the release of intracellular markers. Our data
      suggest that in eukaryotic host cells, intracellular ExoU targets and hydrolyzes
      PI(4,5)P2 on the plasma membrane, causing a subsequent disruption of cellular
      structures and membrane integrity. 

PMID- 25061863
TI  - Stereotactic radiosurgery for brain metastases: a case-matched study comparing
      treatment results for patients 80 years of age or older versus patients 65-79
      years of age.
AB  - OBJECT: Recently, an increasing number of patients with brain metastases, even
      patients over 80 years of age, have been treated with stereotactic radiosurgery
      (SRS). However, there is little information on SRS treatment results for patients
      with brain metastases 80 years of age and older. The authors undertook this study
      to reappraise whether SRS treatment results for patients 80 years of age or older
      differ from those of patients who are 65-79 years old. METHODS: This was an
      institutional review board-approved, retrospective cohort study. Among 2552
      consecutive brain metastasis patients who underwent SRS during the 1998-2011
      period, we studied 165 who were 80 years of age or older (Group A) and 1181 who
      were age 65-79 years old (Group B). Because of the remarkable disproportion in
      patient numbers between the 2 groups and considerable differences in pre-SRS
      clinical factors, the authors conducted a case-matched study using the propensity
      score matching method. Ultimately, 330 patients (165 from each group, A and B)
      were selected. For time-to-event outcomes, the Kaplan-Meier method was used to
      estimate overall survival and competing risk analysis was used to estimate other
      study end points, as appropriate. RESULTS: Although the case-matched study showed
      that post-SRS median survival time (MST, months) was shorter in Group A patients
      (5.3 months, 95% CI 3.9-7.0 months) than in Group B patients (6.9 months, 95% CI
      5.0-8.1 months), this difference was not statistically significant (HR 1.147, 95%
      CI 0.921-1.429, p = 0.22). Incidences of neurological death and deterioration
      were slightly lower in Group A than in Group B patients (6.3% vs 11.8% and 8.5%
      vs 13.9%), but these differences did not reach statistical significance (p = 0.11
      and p = 0.16). Furthermore, competing risk analyses showed that the 2 groups did
      not differ significantly in cumulative incidence of local recurrence (HR 0.830,
      95% CI 0.268-2.573, p = 0.75), rates of repeat SRS (HR 0.738, 95% CI 0.438-1.242,
      p = 0.25), or incidence of SRS-related complications (HR 0.616, 95% CI 0.152
      2.495, p = 0.49). Among the Group A patients, post-SRS MSTs were 11.6 months (95%
      CI 7.8-19.6 months), 7.9 months (95% CI 5.2-10.9 months), and 2.8 months (95% CI;
      2.4-4.6 months) in patients whose disease status was modified-recursive
      partitioning analysis (RPA) Class(es) I+IIa, IIb, and IIc+III, respectively (p <
      0.001). CONCLUSIONS: Our results suggest that patients 80 years of age or older
      are not unfavorable candidates for SRS as compared with those 65-79 years old.
      Particularly, even among patients 80 years and older, those with modified-RPA
      Class I+IIa or IIb disease are considered to be favorable candidates for more
      aggressive treatment of brain metastases.

PMID- 25061864
TI  - Editorial: normal pressure hydrocephalus.

PMID- 25061865
TI  - Outpatient follow-up of nonoperative cerebral contusion and traumatic
      subarachnoid hemorrhage: does repeat head CT alter clinical decision-making?
AB  - OBJECTIVES: Many neurosurgeons obtain repeat head CT at the first clinic follow
      up visit for nonoperative cerebral contusion and traumatic subarachnoid
      hemorrhage (tSAH). The authors undertook a single-center, retrospective study to
      determine whether outpatient CT altered clinical decision-making. METHODS: The
      authors evaluated 173 consecutive adult patients admitted to their institution
      from April 2006 to August 2012 with an admission diagnosis of cerebral contusion
      or tSAH and at least 1 clinic follow-up visit with CT. Patients with epidural,
      subdural, aneurysmal subarachnoid, or intraventricular hemorrhage, and those who
      underwent craniotomy, were excluded. Patient charts were reviewed for new CT
      findings, new patient symptoms, and changes in treatment plan. Patients were
      stratified by neurological symptoms into 3 groups: 1) asymptomatic; 2) mild,
      nonspecific symptoms; and 3) significant symptoms. Mild, nonspecific symptoms
      included minor headaches, vertigo, fatigue, and mild difficulties with
      concentration, short-term memory, or sleep; significant symptoms included
      moderate to severe headaches, nausea, vomiting, focal neurological complaints,
      impaired consciousness, or new cognitive impairment evident on routine clinical
      examination. RESULTS: One hundred seventy-three patients met inclusion criteria,
      with initial clinic follow-up obtained within approximately 6 weeks. Of the 173
      patients, 104 (60.1%) were asymptomatic, 68 patients (39.3%) had mild,
      nonspecific neurological symptoms, and 1 patient (1.0%) had significant
      neurological symptoms. Of the asymptomatic patients, 3 patients (2.9%) had new CT
      findings and 1 of these patients (1.0%) underwent a change in treatment plan
      because of these findings. This change involved an additional clinic appointment
      and CT to monitor a 12-mm chronic subdural hematoma that ultimately resolved
      without treatment. Of the patients with mild, nonspecific neurological symptoms,
      6 patients (8.8%) had new CT findings and 3 of these patients (4.4%) underwent a
      change in treatment plan because of these findings; none of these patients
      required surgical intervention. The single patient with significant neurological
      symptoms did not have any new CT findings. CONCLUSIONS: Repeat outpatient CT of
      asymptomatic patients after nonoperative cerebral contusion and tSAH is very
      unlikely to demonstrate significant new pathology. Given the cost and radiation
      exposure associated with CT, imaging should be reserved for patients with
      significant symptoms or focal findings on neurological examination.

PMID- 25061866
TI  - Meningioma surgery in the era of 5-aminolevulinic acid fluorescence-guided
      surgery.

PMID- 25061867
TI  - Patient outcomes and surgical complications in coccidioidomycosis-related
      hydrocephalus: an institutional review.
AB  - OBJECTIVES: Coccidioidomycosis is a common fungal infection in the southwestern
      US. Hydrocephalus is a serious complication of cranial coccidioidomycosis, and
      the surgical management of coccidioidomycosis-related hydrocephalus has unique
      challenges. The authors reviewed their institutional experience with
      hydrocephalus in the setting of coccidioidomycosis. METHODS: The authors
      retrospectively identified 44 patients diagnosed with coccidioidomycosis-related
      hydrocephalus at their institution since 1990, who underwent a total of 99
      shunting procedures. The authors examined patient demographics, type of shunt and
      valve used, pressure settings, failure rates, medical treatment, ventricular
      response to shunting, and other variables. RESULTS: The majority of patients were
      young (average age 37 years) men (male/female ratio 28:16) with a mean follow-up
      of 63 months. Patients of Asian and African descent were overrepresented in the
      cohort compared with regional demographic data. The overall shunt failure rate
      during follow-up was 50%, and the average number of revisions required if the
      shunt failed was 2.5 (range 1-8). Low to moderate draining pressures (mean 88 mm
      H2O) were used in this cohort. Fourteen patients received intrathecal
      antifungals, and a trend of initiating intrathecal therapy after need for a shunt
      revision was observed (p = 0.051). The majority of shunt failures (81%) were due
      to mechanical blockages in the drainage system. Most patients (59%) had at least
      partial persistent postoperative ventriculomegaly despite successful CSF
      diversion. Four patients (9%) died due to coccidioidomycosis during the follow-up
      period. CONCLUSIONS: Coccidioidomycosis-related hydrocephalus more often affected
      young males in the study's cohort, especially those of African and Asian descent.
      Despite the best medical therapy, there was a high rate of shunt failure due to
      clogged catheters or valves due to the underlying disease process. Many patients
      continued to have ventriculomegaly even with adequate CSF diversion. The
      morbidity and mortality of this chronic disease process must be recognized by the
      treatment team, and patients should be appropriately counseled.

PMID- 25061868
TI  - Residual tumor volume and patient survival following reoperation for recurrent
      glioblastoma.
AB  - OBJECTIVES: Maximal safe tumor resection is part of the standard of care for
      patients with newly diagnosed glioblastoma. The role of reoperation in the care
      of patients with recurrent glioblastoma is less clear, and less than a quarter of
      patients undergo a second surgery. Previous studies have identified preoperative
      variables associated with the improved survival of patients following
      reoperation, and guidelines for the selection of patients for reoperation have
      been devised and validated. In this study, the authors analyzed the relative
      survival benefit of maximal safe tumor removal in a series of patients with
      recurrent glioblastoma who all underwent reoperation. METHODS: In this
      longitudinal study, the clinical and radiological data of 97 consecutive patients
      who underwent reoperation for recurrent glioblastoma were prospectively
      collected. Multiple regression analyses and Kaplan-Meier plotting were performed
      to identify pre- and postoperative clinical and radiological variables associated
      with increased survival following reoperation. RESULTS: The median postoperative
      survival of all patients following reoperation was 12.4 months (95% confidence
      interval [CI] 9.0-15.6 months). Multiple Cox regression analysis revealed that
      patients with large (> 3 cm(3)) residual tumors following reoperation had
      significantly decreased survival relative to those with residual tumors that were
      small (> 0-3 cm(3); hazard ratio [HR] = 3.10, 95% CI 1.69-5.70; p < 0.001) or
      radiologically absent (0 cm(3); HR = 5.82, 95% CI 2.98-11.37; p < 0.001). Large
      residual tumors had faster rates of subsequent regrowth than small (odds ratio
      [OR] = 4.22, 95% CI 1.19-14.97; p = 0.026) or radiologically absent (OR = 11.00,
      95% CI 2.79-43.43; p = 0.001) residual tumors, and a faster regrowth rate was
      significantly associated with decreased survival (HR = 4.01, 95% CI 2.26-7.14; p
      < 0.001). CONCLUSIONS: The overall survival of patients with recurrent
      glioblastoma who underwent reoperations increased with decreasing postoperative
      residual tumor volumes. For patients meeting prognostic criteria for reoperation,
      the surgical goal should be to minimize residual tumor volume to maximize overall
      survival. Clinical trial registration no.: NCT00060541 ( ClinicalTrials.gov ).

PMID- 25061869
TI  - Outcome of modern shunt therapy in patients with idiopathic normal pressure
      hydrocephalus 6 years postoperatively.
AB  - OBJECTIVE: Shunt therapy in idiopathic normal pressure hydrocephalus (iNPH) can
      improve symptoms in 84% of patients 1 year postoperatively. Therefore,
      implantation of a ventriculoperitoneal shunt (VPS) prevents or at least prolongs
      the time during which patients are not dependent on care from others because of
      gait disorder or dementia. In this study, the medium-term results of modern shunt
      therapy were evaluated. METHODS: The authors retrospectively studied outcome in
      iNPH patients in whom VPSs were implanted. At yearly follow-up examinations over
      at least 6 years, clinical symptoms were recorded according to the NPH recovery
      rate (NPH-RR): (preoperative Kiefer Scale [KS] score - postoperative KS
      score)/(preoperative KS score * 10). Time and cause of death over this period
      were also analyzed. RESULTS: Among the 147 patients treated for iNPH in the
      period between 1997 and 2006, 69 had died at the time of the authors' survey.
      Sixty-one patients reached the 6-year examination. The median age was 64 years
      (range 33-83 years) at the time of VPS implantation and 73 years (range 41-91
      years) at the time of this study. Six years after shunt implantation, the median
      KS score was significantly lower than the preoperative score (4.3 vs 8.1 points).
      Fifty-nine percent of 61 patients had an excellent outcome, 15% had satisfactory
      benefit, and 26% had unsatisfactory results 6 years postoperatively. Three of the
      147 patients who underwent implantation of a VPS died of cerebral diseases 4-10
      years postoperatively. CONCLUSIONS: Implantation of a VPS is a safe procedure and
      can improve symptoms in 74% of patients with iNPH in the longer term.

PMID- 25061870
TI  - Commentary: abortion provider stigma and mainstream medicine.
AB  - This commentary describes the various manifestations of the stigmatization and
      marginalized status of abortion providers in relation to mainstream medicine. The
      article also addresses some of the current efforts to respond to this
      stigmatization.

PMID- 25061871
TI  - Schlemm's canal: more than meets the eye, lymphatics in disguise.
AB  - Schlemm's canal (SC) is a unique vascular structure that functions to maintain
      fluid homeostasis by draining aqueous humor from the eye into the systemic
      circulation. The endothelium lining the inner wall of SC has both blood and
      lymphatic vascular characteristics, thus prompting exploration of the development
      and regulation of this unique channel. In this issue of the JCI, back-to-back
      papers by Aspelund et al. and Park et al. detail the mechanisms of SC
      development, which includes a lymphatic reprogramming that is necessary to
      maintain proper function. Furthermore, both groups exploit the lymph-like
      qualities of this canal: they identify VEGF-C as a potential therapeutic for
      glaucoma and suggest that expression of PROX1, a marker of lymphatic fate, could
      also serve as a biosensor for monitoring SC integrity. These studies provide
      substantial insight into the molecular and cellular pathways that govern SC
      development and reveal that ocular pathology is associated with deregulation of
      the lymph-like characteristics of SC. 

PMID- 25061872
TI  - Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes.
AB  - The endocannabinoid system (ECS) regulates multiple physiological processes,
      including cutaneous cell growth and differentiation. Here, we explored the
      effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)
      cannabidiol (CBD), on human sebaceous gland function and determined that CBD
      behaves as a highly effective sebostatic agent. Administration of CBD to cultured
      human sebocytes and human skin organ culture inhibited the lipogenic actions of
      various compounds, including arachidonic acid and a combination of linoleic acid
      and testosterone, and suppressed sebocyte proliferation via the activation of
      transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of
      TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the
      downregulation of nuclear receptor interacting protein-1 (NRIP1), which
      influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis.
      CBD also exerted complex antiinflammatory actions that were coupled to A2a
      adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and
      inhibition of the NF-kappaB signaling. Collectively, our findings suggest that,
      due to the combined lipostatic, antiproliferative, and antiinflammatory effects,
      CBD has potential as a promising therapeutic agent for the treatment of acne
      vulgaris. 

PMID- 25061873
TI  - IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset.
AB  - Invariant natural killer T (iNKT) cells rapidly produce copious amounts of
      multiple cytokines after activation, thereby impacting a wide variety of
      different immune reactions. However, strong activation of iNKT cells with alpha
      galactosylceramide (alphaGalCer) reportedly induces a hyporeactive state that
      resembles anergy. In contrast, we determined here that iNKT cells from mice
      pretreated with alphaGalCer retain cytotoxic activity and maintain the ability to
      respond to TCR-dependent as well as TCR-independent cytokine-mediated
      stimulation. Additionally, alphaGalCer-pretreated iNKT cells acquired
      characteristics of regulatory cells, including production and secretion of the
      immunomodulatory cytokine IL-10. Through the production of IL-10, alphaGalCer
      pretreated iNKT cells impaired antitumor responses and reduced disease in
      experimental autoimmune encephalomyelitis, a mouse model of autoimmune disease.
      Furthermore, a subset of iNKT cells with a similar inhibitory phenotype and
      function were present in mice not exposed to alphaGalCer and were enriched in
      mouse adipose tissue and detectable in human PBMCs. These data demonstrate that
      IL-10-producing iNKT cells with regulatory potential (NKT10 cells) represent a
      distinct iNKT cell subset. 

PMID- 25061874
TI  - EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted
      tumorigenesis.
AB  - Aberrant activation of EGFR in human cancers promotes tumorigenesis through
      stimulation of AKT signaling. Here, we determined that the discoidina neuropilin
      like membrane protein DCBLD2 is upregulated in clinical specimens of
      glioblastomas and head and neck cancers (HNCs) and is required for EGFR
      stimulated tumorigenesis. In multiple cancer cell lines, EGFR activated
      phosphorylation of tyrosine 750 (Y750) of DCBLD2, which is located within a
      recently identified binding motif for TNF receptor-associated factor 6 (TRAF6).
      Consequently, phosphorylation of DCBLD2 Y750 recruited TRAF6, leading to
      increased TRAF6 E3 ubiquitin ligase activity and subsequent activation of AKT,
      thereby enhancing EGFR-driven tumorigenesis. Moreover, evaluation of patient
      samples of gliomas and HNCs revealed an association among EGFR activation, DCBLD2
      phosphorylation, and poor prognoses. Together, our findings uncover a pathway in
      which DCBLD2 functions as a signal relay for oncogenic EGFR signaling to promote
      tumorigenesis and suggest DCBLD2 and TRAF6 as potential therapeutic targets for
      human cancers that are associated with EGFR activation. 

PMID- 25061875
TI  - Shifting FcgammaRIIA-ITAM from activation to inhibitory configuration ameliorates
      arthritis.
AB  - Rheumatoid arthritis-associated (RA-associated) inflammation is mediated through
      the interaction between RA IgG immune complexes and IgG Fc receptors on immune
      cells. Polymorphisms within the gene encoding the human IgG Fc receptor IIA
      (hFcgammaRIIA) are associated with an increased risk of developing RA. Within the
      hFcgammaRIIA intracytoplasmic domain, there are 2 conserved tyrosine residues
      arranged in a noncanonical immunoreceptor tyrosine-based activation motif (ITAM).
      Here, we reveal that inhibitory engagement of the hFcgammaRIIA ITAM either with
      anti-hFcgammaRII F(ab')2 fragments or intravenous hIgG (IVIg) ameliorates RA
      associated inflammation, and this effect was characteristic of previously
      described inhibitory ITAM (ITAMi) signaling for hFcalphaRI and hFcgammaRIIIA, but
      only involves a single tyrosine. In hFcgammaRIIA-expressing mice, arthritis
      induction was inhibited following hFcgammaRIIA engagement. Moreover, hFcgammaRIIA
      ITAMi-signaling reduced ROS and inflammatory cytokine production through
      inhibition of guanine nucleotide exchange factor VAV-1 and IL-1 receptor
      associated kinase 1 (IRAK-1), respectively. ITAMi signaling was mediated by
      tyrosine 304 (Y304) within the hFcgammaRIIA ITAM, which was required for
      recruitment of tyrosine kinase SYK and tyrosine phosphatase SHP-1. Anti
      hFcgammaRII F(ab')2 treatment of inflammatory synovial cells from RA patients
      inhibited ROS production through induction of ITAMi signaling. These data suggest
      that shifting constitutive hFcgammaRIIA-mediated activation to ITAMi signaling
      could ameliorate RA-associated inflammation. 

PMID- 25061876
TI  - Proteasome function is required for platelet production.
AB  - The proteasome inhibiter bortezomib has been successfully used to treat patients
      with relapsed multiple myeloma; however, many of these patients become
      thrombocytopenic, and it is not clear how the proteasome influences platelet
      production. Here we determined that pharmacologic inhibition of proteasome
      activity blocks proplatelet formation in human and mouse megakaryocytes. We also
      found that megakaryocytes isolated from mice deficient for PSMC1, an essential
      subunit of the 26S proteasome, fail to produce proplatelets. Consistent with
      decreased proplatelet formation, mice lacking PSMC1 in platelets (Psmc1(fl/fl)
      Pf4-Cre mice) exhibited severe thrombocytopenia and died shortly after birth. The
      failure to produce proplatelets in proteasome-inhibited megakaryocytes was due to
      upregulation and hyperactivation of the small GTPase, RhoA, rather than NF
      kappaB, as has been previously suggested. Inhibition of RhoA or its downstream
      target, Rho-associated protein kinase (ROCK), restored megakaryocyte proplatelet
      formation in the setting of proteasome inhibition in vitro. Similarly, fasudil, a
      ROCK inhibitor used clinically to treat cerebral vasospasm, restored platelet
      counts in adult mice that were made thrombocytopenic by tamoxifen-induced
      suppression of proteasome activity in megakaryocytes and platelets (Psmc1(fl/fl)
      Pdgf-Cre-ER mice). These results indicate that proteasome function is critical
      for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential
      strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma
      patients.

PMID- 25061877
TI  - Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity.
AB  - Schlemm's canal (SC) is a specialized vascular structure in the eye that
      functions to drain aqueous humor from the intraocular chamber into systemic
      circulation. Dysfunction of SC has been proposed to underlie increased aqueous
      humor outflow (AHO) resistance, which leads to elevated ocular pressure, a factor
      for glaucoma development in humans. Here, using lymphatic and blood vasculature
      reporter mice, we determined that SC, which originates from blood vessels during
      the postnatal period, acquires lymphatic identity through upregulation of
      prospero homeobox protein 1 (PROX1), the master regulator of lymphatic
      development. SC expressed lymphatic valve markers FOXC2 and integrin alpha9 and
      exhibited continuous vascular endothelial-cadherin (VE-cadherin) junctions and
      basement membrane, similar to collecting lymphatics. SC notably lacked luminal
      valves and expression of the lymphatic endothelial cell markers podoplanin and
      lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Using an ocular
      puncture model, we determined that reduced AHO altered the fate of SC both during
      development and under pathologic conditions; however, alteration of VEGF-C/VEGFR3
      signaling did not modulate SC integrity and identity. Intriguingly, PROX1
      expression levels linearly correlated with SC functionality. For example, PROX1
      expression was reduced or undetectable under pathogenic conditions and in
      deteriorated SCs. Collectively, our data indicate that PROX1 is an accurate and
      reliable biosensor of SC integrity and identity. 

PMID- 25061878
TI  - The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.
AB  - In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite
      striking structural and functional similarities with the lymphatic vascular
      system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we
      demonstrated the expression of lymphatic endothelial cell markers by the SC in
      murine and zebrafish models as well as in human eye tissue. The initial stages of
      SC development involved induction of the transcription factor PROX1 and the
      lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in
      postnatal mice. Using gene deletion and function-blocking antibodies in mice, we
      determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR
      3, are essential for SC development. Delivery of VEGF-C into the adult eye
      resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas
      VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of
      recombinant VEGF-C induced SC growth and was associated with trend toward a
      sustained decrease in intraocular pressure in adult mice. These results reveal
      the evolutionary conservation of the lymphatic-like phenotype of the SC,
      implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and
      provide a basis for further studies on therapeutic manipulation of the SC with
      VEGF-C in glaucoma treatment. 

PMID- 25061879
TI  - Targeted p16(Ink4a) epimutation causes tumorigenesis and reduces survival in
      mice.
AB  - Cancer has long been viewed as a genetic disease; however, epigenetic silencing
      as the result of aberrant promoter DNA methylation is frequently associated with
      cancer development, suggesting an epigenetic component to the disease.
      Nonetheless, it has remained unclear whether an epimutation (an aberrant change
      in epigenetic regulation) can induce tumorigenesis. Here, we exploited a
      functionally validated cis-acting regulatory element and devised a strategy to
      induce developmentally regulated genomic targeting of DNA methylation. We used
      this system to target DNA methylation within the p16(Ink4a) promoter in mice in
      vivo. Engineered p16(Ink4a) promoter hypermethylation led to transcriptional
      suppression in somatic tissues during aging and increased the incidence of
      spontaneous cancers in these mice. Further, mice carrying a germline p16(Ink4a)
      mutation in one allele and a somatic epimutation in the other had accelerated
      tumor onset and substantially shortened tumor-free survival. Taken together,
      these results provide direct functional evidence that p16(Ink4a) epimutation
      drives tumor formation and malignant progression and validate a targeted
      methylation approach to epigenetic engineering.

PMID- 25061881
TI  - Culture and maternity care in Kazakhstan: what new mothers expected.
AB  - Maternity care in the developing nation of Kazakhstan has been characterized as
      low in quality, with mothers having low levels of health knowledge. Some
      nongovernmental organizations have been offering childbirth preparation courses
      to address the lack of knowledge and encourage participation and decision making
      among expecting mothers. The participants of this study, however, report that
      information is more for preparation than for decision making, and that the
      relational aspects of their care, namely, emotional support and trust, are most
      important. This emphasis reflects the cultural and historical influences that
      need to be considered when adopting foreign models of care and health education. 

PMID- 25061880
TI  - Expression profiling of RNA transcripts during neuronal maturation and ischemic
      injury.
AB  - Neuronal development is a pro-survival process that involves neurite growth,
      synaptogenesis, synaptic and neuronal pruning. During development, these
      processes can be controlled by temporal gene expression that is orchestrated by
      both long non-coding RNAs and microRNAs. To examine the interplay between these
      different components of the transcriptome during neuronal differentiation, we
      carried out mRNA, long non-coding RNA and microRNA expression profiling on
      maturing primary neurons. Subsequent gene ontology analysis revealed regulation
      of axonogenesis and dendritogenesis processes by these differentially expressed
      mRNAs and non-coding RNAs. Temporally regulated mRNAs and their associated long
      non-coding RNAs were significantly over-represented in proliferation and
      differentiation associated signalling, cell adhesion and neurotrophin signalling
      pathways. Verification of expression of the Axin2, Prkcb, Cntn1, Ncam1, Negr1,
      Nrxn1 and Sh2b3 mRNAs and their respective long non-coding RNAs in an in vitro
      model of ischemic-reperfusion injury showed an inverse expression profile to the
      maturation process, thus suggesting their role(s) in maintaining neuronal
      structure and function. Furthermore, we propose that expression of the cell
      adhesion molecules, Ncam1 and Negr1 might be tightly regulated by both long non
      coding RNAs and microRNAs. 

PMID- 25061882
TI  - Moxibustion treatment for knee osteoarthritis: a multi-centre, non-blinded,
      randomised controlled trial on the effectiveness and safety of the moxibustion
      treatment versus usual care in knee osteoarthritis patients.
AB  - INTRODUCTION: This study tested the effectiveness of moxibustion on pain and
      function in chronic knee osteoarthritis (KOA) and evaluated safety. METHODS: A
      multi-centre, non-blinded, parallel-group, randomised controlled trial compared
      moxibustion with usual care (UC) in KOA. 212 South Korean patients aged 40-70
      were recruited from 2011-12, stratified by mild (Kellgren/Lawrence scale grades
      0/1) and moderate-severe KOA (grades 2/3/4), and randomly allocated to
      moxibustion or UC for four weeks. Moxibustion involved burning mugwort devices
      over acupuncture and Ashi points in affected knee(s). UC was allowed. Korean
      Western Ontario and McMaster Universities Questionnaire (K-WOMAC), Short Form 36
      Health Survey (SF-36v2), Beck Depression Inventory (BDI), physical performance
      test, pain numeric rating scale (NRS) and adverse events were evaluated at 5 and
      13 weeks. K-WOMAC global score at 5 weeks was the primary outcome. RESULTS: 102
      patients (73 mild, 29 moderate-severe) were allocated to moxibustion, 110 (77
      mild, 33 moderate-severe) to UC. K-WOMAC global score (moxibustion 25.42+/-SD
      19.26, UC 33.60+/-17.91, p<0.01, effect size = 0.0477), NRS (moxibustion 44.77+/
      22.73, UC 56.23+/-17.71, p<0.01, effect size = 0.0073) and timed-stand test
      (moxibustion 24.79+/-9.76, UC 25.24+/-8.84, p = 0.0486, effect size  = 0.0021)
      were improved by moxibustion at 5 weeks. The primary outcome improved for mild
      but not moderate-severe KOA. At 13 weeks, moxibustion significantly improved the
      K-WOMAC global score and NRS. Moxibustion improved SF-36 physical component
      summary (p = 0.0299), bodily pain (p = 0.0003), physical functioning (p = 0.0025)
      and social functioning (p = 0.0418) at 5 weeks, with no difference in mental
      component summary at 5 and 13 weeks. BDI showed no difference (p = 0.34) at 5
      weeks. After 1158 moxibustion treatments, 121 adverse events included first (n =
      6) and second degree (n = 113) burns, pruritus and fatigue (n = 2). CONCLUSIONS:
      Moxibustion may improve pain, function and quality of life in KOA patients, but
      adverse events are common. Limitations included no sham control or blinding.
      TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0000130.

PMID- 25061884
TI  - Association between polymorphisms in the TSHR gene and Graves' orbitopathy.
AB  - BACKGROUND: Graves' orbitopathy (GO) as well as Graves' disease (GD)
      hyperthyroidism originate from an autoimmune reaction against the common auto
      antigen, thyroid-stimulating hormone receptor (TSHR). GO phenotype is associated
      with environmental risk factors, mainly nicotinism, as well as genetic risk
      factors which initiate an immunologic reaction. In some patients GO is observed
      before diagnosis of GD hyperthyroidism, while it can also be observed far after
      diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus,
      the pathogenesis of GD and GO may correlate with different genetic backgrounds,
      which has been confirmed by studies of correlations between GO and polymorphisms
      in cytokines involved in orbit inflammation. The aim of our analysis was to
      assess genetic predisposition to GO in young patients (age of diagnosis <=30
      years of age), for whom environmental effects had less time to influence outcomes
      than in adults. METHODS: 768 GD patients were included in the study. 359 of them
      had clinically evident orbitopathy (NOSPECS >=2). Patients were stratified by age
      at diagnosis. Association analyses were performed for genes with a known
      influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4
      (CTLA4) and lymphoid protein tyrosine phosphatase (PTPN22). RESULTS: The rs179247
      TSHR polymorphism was associated with GO in young patients only. In young GO-free
      patients, allele A was statistically more frequent and homozygous carriers had a
      considerable lower risk of disease incidence than patients with AG or GG
      genotypes. Those differences were not found in either elderly patients or the
      group analyzed as a whole. CONCLUSIONS: Allele A of the rs179247 polymorphism in
      the TSHR gene is associated with lower risk of GO in young GD patients.

PMID- 25061885
TI  - Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and
      flurbiprofen.
AB  - BACKGROUND: In addition to their effects upon prostaglandin synthesis, the non
      steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the
      metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide
      (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH),
      respectively. Here, we investigated whether these effects upon endocannabinoid
      metabolism are shared by the main metabolites of ibuprofen and flurbiprofen.
      METHODOLOGY/PRINCIPAL FINDINGS: COX activities were measured via changes in
      oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and
      arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring
      hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of
      ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at
      lower concentrations than the oxygenation of arachidonic acid was seen with 4'
      hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower
      potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites
      retained the ability to inhibit FAAH in a pH-dependent manner, although the
      potency was lower than seen with the parent compounds. CONCLUSIONS/SIGNIFICANCE:
      It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain
      some of the properties of the parent compound with respect to inhibition of
      endocannabinoid metabolism. However, these effects are unlikely to contribute to
      the actions of the parent compounds in vivo.

PMID- 25061886
TI  - Electrochemical and sonoelectrochemical processes applied to amaranth dye
      degradation.
AB  - Amaranth dye is an organic compound largely used in the food and beverage
      industries with potential toxicity effects on humans. It can be found as a
      pollutant species in aquatic environments and has been classified as an endocrine
      disruptor. This study describes amaranth degradation upon ultrasonication
      associated with an electrochemical system that uses a boron-doped diamond anode
      BDD, defined as a sonoelectrochemical process. Ninety-minute electrolyses were
      performed using current densities in the 10-50 mA cm(-2) range, and the
      concentration decay, pH, energy and current efficiencies, as well as the
      discoloration rate were evaluated. The amaranth concentration decayed as a
      function of electrolysis time and the reactions obeyed pseudo first-order
      kinetics, with an apparent constant rate between 10(-1) and 10(-3)min(-1). The
      electrochemical and sonoelectrochemical processes at 35 mA cm(-2) yielded TOC
      removal values between 92.1% and 95.1% respectively, after 90 min. Current
      efficiency values obtained for both processes were 18.2% and 23.6%. Exhaustive 5h
      electrolysis was performed and the degradation products were identified by HPLC
      MS. A mechanism for the degradation of amaranth was proposed based on an analysis
      of the aromatic and aliphatic intermediates.

PMID- 25061887
TI  - Evidence for cooperative mineralization of diuron by Arthrobacter sp. BS2 and
      Achromobacter sp. SP1 isolated from a mixed culture enriched from diuron exposed
      environments.
AB  - Diuron was found to be mineralized in buffer strip soil (BS) and in the sediments
      (SED) of the Morcille river in the Beaujolais vineyard repeatedly treated with
      this herbicide. Enrichment cultures from BS and SED samples led to the isolation
      of three bacterial strains transforming diuron to 3,4-dichloroaniline (3,4-DCA)
      its aniline derivative. 16S rRNA sequencing revealed that they belonged to the
      genus Arthrobacter (99% of similarity to Arthrobacter globiformis strain K01-01)
      and were designated as Arthrobacter sp. BS1, BS2 and SED1. Diuron-degrading
      potential characterized by sequencing of the puhA gene, characterizing the diuron
      degradaing potential, revealed 99% similarity to A. globiformis strain D47 puhA
      gene isolated a decade ago in the UK. These isolates were also able to use
      chlorotoluron for their growth. Although able to degrade linuron and monolinuron
      to related aniline derivatives they were not growing on them. Enrichment cultures
      led to the isolation of a strain from the sediments entirely degrading 3,4-DCA.
      16S rRNA sequence analysis showed that it was affiliated to the genus
      Achromobacter (99% of similarity to Achromobacter sp. CH1) and was designated as
      Achromobacter sp. SP1. The dcaQ gene encoding enzyme responsible for the
      transformation of 3,4-DCA to chlorocatechol was found in SP1 with 99% similarity
      to that of Comamonas testosteroni WDL7. This isolate also used for its growth a
      range of anilines (3-chloro-4-methyl-aniline, 4-isopropylaniline, 4
      chloroaniline, 3-chloroaniline, 4-bromoaniline). The mixed culture composed of
      BS2 and SP1 strains entirely mineralizes (14)C-diuron to (14)CO2. Diuron
      mineralization observed in the enrichment culture could result from the metabolic
      cooperation between these two populations. 

PMID- 25061888
TI  - NACCHO's national community of practice support for local evidenced-based chronic
      disease self-management program.

PMID- 25061889
TI  - Population health: no one does it alone.

PMID- 25061890
TI  - Independent state health surveys: responding to the need for local population
      health data.
AB  - CONTEXT: There is high demand for local-level population health data. A national
      system of state and local data collection would help improve both population
      health and health care delivery. The primary source of state-level population
      health data for adults is the Behavioral Risk Factor Surveillance System.
      However, many states need data on children and adolescents, racial and ethnic
      subpopulations, consistent estimates for localities, or more in-depth information
      on key topics than the Behavioral Risk Factor Surveillance System provides.
      Eleven state health surveys (SHSs) have emerged in an effort to address these
      gaps. DESIGN: Semistructured telephone interviews were conducted in 2009 with
      representatives of 9 SHSs. The interviews were recorded, and data were
      transcribed, organized, and analyzed according to the query structure. This
      analysis identified (1) the core elements of SHS that have been successful in
      meeting needs for local data and (2) the processes and strategies used by state
      officials in creating these surveys. RESULTS: Key findings include the following:
      (1) SHSs provide concrete data on local health issues that meet the needs of
      policy makers who wish to adopt evidence-based public health policies; (2) data
      from SHSs allow researchers to identify issues, apply for grants, and evaluate,
      assess, and track health indicators; (3) a "champion" is required to build the
      case for a survey and push through barriers to obtain funding and stakeholder buy
      in; and (4) SHSs face challenges such as inconsistent funding and lack of uniform
      standards. CONCLUSION: Opportunities to support SHSs include (1) identifying
      sustained funding sources; (2) providing technical assistance and facilitating
      training to foster best practices, quality standards, and comparability across
      states; and (3) supporting an organization for SHS researchers to share
      resources, information, and experiences.

PMID- 25061891
TI  - Effective atomic numbers, water and tissue equivalence properties of human
      tissues, tissue equivalents and dosimetric materials for total electron
      interaction in the energy region 10 keV-1 GeV.
AB  - Effective atomic numbers (Zeff) of 107 different materials of dosimetric interest
      have been calculated for total electron interactions in the wide energy region
      10keV-1GeV. The stopping cross sections of elements and dosimetric materials were
      used to calculate Zeff of the materials. Differences (%) in Zeff relative to
      water have been calculated in the entire energy region to evaluate the water
      equivalency of the used materials. Moreover, the tissue equivalent materials have
      been compared with the tissues and dosimetric materials in terms of Zeff to
      reveal their ability to use as tissue substitutes. Possible conclusions were
      drawn based on the variation of Zeff through the entire energy region and water
      and tissue equivalency comparisons in terms of Zeff. 

PMID- 25061892
TI  - Environmental side effects of pharmaceutical cocktails: what we know and what we
      should know.
AB  - Cocktails of pharmaceuticals are released in the environment after human
      consumption and due to the incomplete removal at the wastewater treatment plants.
      Pharmaceuticals are considered as contaminants of emerging concern and, a
      plethora of journal articles addressing their possible adverse effects have been
      published during the past 20 years. The emphasis during the early years of
      research within this field, was on the assessment of acute effects of
      pharmaceuticals applied singly, leading to results regarding their environmental
      risk, potentially not realistic or relevant to the actual environmental
      conditions. Only recently has the focus been shifted to chronic exposure and to
      the assessment of cocktail effects. To this end, this review provides an up-to
      date compilation of 57 environmental and human toxicology studies published
      during 2000-2014 dealing with the adverse effects of pharmaceutical mixtures. The
      main challenges regarding the design of experiments and the analysis of the
      results regarding the effects of pharmaceutical mixtures to different biological
      systems are presented and discussed herein. The gaps of knowledge are critically
      reviewed highlighting specific future research needs and perspectives. 

PMID- 25061893
TI  - Social looking, social referencing and humor perception in 6- and-12-month-old
      infants.
AB  - Social referencing refers to infants' use of caregivers as emotional referents in
      ambiguous situations (Walden, 1993). Studies of social referencing typically
      require ambulation, thereby over-looking younger, non-ambulatory infants (i.e.,
      <=8-months) and resulting in a widespread assumption that young infants do not
      employ this strategy. Using a novel approach that does not require mobility, we
      found that when parents provided unsolicited affective cues during an ambiguous
      absurd (i.e., humorous) event, 6-month-olds employ one component of social
      referencing, social looking Additionally, 6-month-olds who did not laugh at the
      event were significantly more likely to look toward parents than their
      counterparts who found the event funny. Sequential analyses revealed that,
      following a reference to a smiling parent, 6-month olds were more likely to smile
      at the parent, but by 12 months were more likely to smile at the event suggesting
      that older infants are influenced by parental affect in humorous situations. The
      developmental implications of these findings are discussed, as well as the
      usefulness of studying humor for understanding important developmental phenomena.

PMID- 25061894
TI  - The influence of parents, older siblings, and non-parental care on infant
      development at nine months of age.
AB  - BACKGROUND: The majority of research examining the influence of social
      environment on early child development suggests benefits to two-parent
      households, but contradictory evidence for the effects of siblings. The aims of
      the present study were to examine the influence of the child's proximal social
      environment, and the effects of interactions between socioeconomic status and
      social environment on developmental outcomes. METHODS: Primary caregivers of a
      representative sample of 10,748 nine-month-old infants in Ireland completed the
      Ages and Stages Questionnaire and provided information on social environment.
      Adjustment was made for infant and maternal characteristics, household income,
      and area where the child was living at the time of the study. Further analyses
      tested for interactions between social environment and household income. RESULTS:
      Binary logistic regressions indicated no effects for number of parents in the
      household. However, the presence of siblings in the household was a consistent
      predictor of failing to reach milestones in communication, gross motor, problem
      solving, and personal-social development. Furthermore, there was a gradient of
      increasing likelihood of failing in gross motor, problem-solving, and personal
      social development with increasing numbers of siblings. Care by a grandparent
      decreased the likelihood of failing in communication and personal-social
      development. CONCLUSIONS: These findings do not support the majority of research
      that finds positive benefits for two-parent households. Similarly, the findings
      suggest limited effects for non-parental care. However, the observed negative
      effects of siblings support both the confluence and resource dilution models of
      sibling effect. Examination of follow-up data may elucidate current findings.

PMID- 25061895
TI  - Epigenetic regulation and functional exaptation of transposable elements in
      higher plants.
AB  - Transposable elements (TEs) are mobile genetic elements that can proliferate in
      their host genomes. Because of their robust amplification, TEs have long been
      considered 'selfish DNA', harmful insertions that can threaten host genome
      integrity. The idea of TEs as junk DNA comes from analysis of epigenetic
      silencing of their mobility in plants and animals. This idea contrasts with
      McClintock's characterization of TEs as 'controlling elements'. Emerging studies
      on the regulatory functions of TEs in plant genomes have updated McClintock's
      characterization, indicating exaptation of TEs for genetic regulation. In this
      review, we summarize recent progress in TE silencing, particularly in Arabidopsis
      and rice, and show that TEs provide an abundant, natural source of regulation for
      the host genome. 

PMID- 25061896
TI  - Shedding light on integrative GA signaling.
AB  - Gibberellic acid (GA) regulates a diversity of processes associated with plant
      growth and development. The DELLA proteins act as repressors of GA signaling, and
      are destabilized by GA. Although it is known that GA signaling integrates various
      endogenous and environmental signals, the molecular basis of their modulation of
      plant growth and development is only now beginning to be understood. The current
      suggestion is that the DELLA proteins act as one possible quantitative modulator
      of plant growth, achieved by integrating multiple environmental and hormonal
      signals via protein-protein interactions. This review discusses recent
      elaborations of the de-repression model proposed to describe the GA response, and
      focuses on integrative networks thought to regulate plant growth, development and
      the adaptation to a fluctuating environment. 

PMID- 25061897
TI  - Beyond repression of photomorphogenesis: role switching of COP/DET/FUS in light
      signaling.
AB  - Light is a pivotal environmental stimulus that promotes plant photomorphogenesis.
      Substantial progress has been achieved in defining the central repressors of
      photomorphogenesis, the CONSTITUTIVE PHOTOMORPHOGENIC/DE-ETIOLATED/FUSCA
      (COP/DET/FUS) loci, in the past 20 years. COP/DET/FUS proteins are well
      conserved, and regulate a variety of biological processes in plants and animals.
      The fact that these proteins contribute to the repression of plant
      photomorphogenesis by regulating the ubiquitin-proteasome-dependent pathway has
      been well established. Recently, molecular insight has been gained into the
      functional diversity of COP/DET/FUS. Here, we review the current research on the
      roles of COP/DET/FUS, with a focus on the functional conversion of COP1 in
      photomorphogenesis. 

PMID- 25061898
TI  - Green toxicology.
AB  - Historically, early identification and characterization of adverse effects of
      industrial chemicals was difficult because conventional toxicological test
      methods did not meet R&D needs for rapid, relatively inexpensive methods amenable
      to small amounts of test material. The pharmaceutical industry now front-loads
      toxicity testing, using in silico, in vitro, and less demanding animal tests at
      earlier stages of product development to identify and anticipate undesirable
      toxicological effects and optimize product development. The Green Chemistry
      movement embraces similar ideas for development of less toxic products, safer
      processes, and less waste and exposure. Further, the concept of benign design
      suggests ways to consider possible toxicities before the actual synthesis and to
      apply some structure/activity rules (SAR) and in silico methods. This requires
      not only scientific development but also a change in corporate culture in which
      synthetic chemists work with toxicologists. An emerging discipline called Green
      Toxicology (Anastas, 2012) provides a framework for integrating the principles of
      toxicology into the enterprise of designing safer chemicals, thereby minimizing
      potential toxicity as early in production as possible. Green Toxicology's novel
      utility lies in driving innovation by moving safety considerations to the
      earliest stage in a chemical's lifecycle, i.e., to molecular design. In
      principle, this field is no different than other subdisciplines of toxicology
      that endeavor to focus on a specific area - for example, clinical, environmental
      or forensic toxicology. We use the same principles and tools to evaluate an
      existing substance or to design a new one. The unique emphasis is in using 21st
      century toxicology tools as a preventative strategy to "design out" undesired
      human health and environmental effects, thereby increasing the likelihood of
      launching a successful, sustainable product. Starting with the formation of a
      steering group and a series of workshops, the Green Toxicology concept is
      currently spreading internationally and is being refined via an iterative
      process.

PMID- 25061899
TI  - Consensus report on the future of animal-free systemic toxicity testing.
AB  - Since March 2013, animal use for cosmetics testing for the European market has
      been banned. This requires a renewed view on risk assessment in this field.
      However, in other fields as well, traditional animal experimentation does not
      always satisfy requirements in safety testing, as the need for human-relevant
      information is ever increasing. A general strategy for animal-free test
      approaches was outlined by the US National Research Council's vision document for
      Toxicity Testing in the 21st Century in 2007. It is now possible to provide a
      more defined roadmap on how to implement this vision for the four principal areas
      of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity,
      reproductive toxicity and allergy induction (skin sensitization), as well as for
      the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe
      assembled experts from Europe, America and Asia to design a scientific roadmap
      for future risk assessment approaches and the outcome was then further discussed
      and refined in two consensus meetings with over 200 stakeholders. The key
      recommendations include: focusing on improving existing methods rather than
      favoring de novo design; combining hazard testing with toxicokinetics
      predictions; developing integrated test strategies; incorporating new high
      content endpoints to classical assays; evolving test validation procedures;
      promoting collaboration and data-sharing of different industrial sectors;
      integrating new disciplines, such as systems biology and high throughput
      screening; and involving regulators early on in the test development process. A
      focus on data quality, combined with increased attention to the scientific
      background of a test method, will be important drivers. Information from each
      test system should be mapped along adverse outcome pathways. Finally,
      quantitative information on all factors and key events will be fed into systems
      biology models that allow a probabilistic risk assessment with flexible
      adaptation to exposure scenarios and individual risk factors.

PMID- 25061900
TI  - Developing microphysiological systems for use as regulatory tools--challenges and
      opportunities.

PMID- 25061901
TI  - 3Rs and new frontiers in laboratory techniques.

PMID- 25061902
TI  - National workshop/CME on alternatives to animal experimentation in medical
      science education.

PMID- 25061903
TI  - Animal testing--science or tradition? What future for alternatives to animal
      testing?

PMID- 25061904
TI  - Social media and online attention as an early measure of the impact of research
      in solid organ transplantation.
AB  - INTRODUCTION: Traditional measures of the impact of published research, such as
      citation counts, are limited to measuring academic impact. The use of social
      media and other online tools as alternative measures of research impact is
      gaining popularity and used by leading medical journals. METHODS: MEDLINE was
      searched for articles published with subject headings relating to solid organ
      transplantation between August 1, 2011, and July 31, 2012. Citation data were
      retrieved from SCOPUS, and statistics regarding mentions in social media, social
      bookmarking sites, news outlets, and expert recommendation sites were retrieved
      from the data at www.altmetric.com. Data were analyzed for associations between
      alternative metric data and citation rates. RESULTS: The search retrieved 6,981
      publications. Sixty-six percent of the articles had at least one citation.
      Mentions in social media were 19.3%, 13.1% had social bookmarks, 0.9% had expert
      recommendations, and online news outlets picked up eight articles. Significantly
      higher citation rates were associated with mention in social media, expert
      recommendation, social bookmarking, and for articles identified as meta-analyses,
      multicenter studies, randomized controlled trials, and reviews (all P<0.001). The
      odds of an article being highly cited were significantly increased by a mention
      in social media (odds ratio, 2.58; P<0.001). Qualitative analysis suggests that
      article topics discussed on social media are more likely to relate to the more
      controversial and emotive areas of transplantation. DISCUSSION: Social media and
      online attention act as early predictors of the impact of transplant research as
      measured by later citation rate. Blogging and expert recommendation, in
      particular, are associated with higher citation rates.

PMID- 25061905
TI  - Statistics provide guidance for indigenous organic carbon detection on Mars
      missions.
AB  - Data from the Viking and Mars Science Laboratory missions indicate the presence
      of organic compounds that are not definitively martian in origin. Both
      contamination and confounding mineralogies have been suggested as alternatives to
      indigenous organic carbon. Intuitive thought suggests that we are repeatedly
      obtaining data that confirms the same level of uncertainty. Bayesian statistics
      may suggest otherwise. If an organic detection method has a true positive to
      false positive ratio greater than one, then repeated organic matter detection
      progressively increases the probability of indigeneity. Bayesian statistics also
      reveal that methods with higher ratios of true positives to false positives give
      higher overall probabilities and that detection of organic matter in a sample
      with a higher prior probability of indigenous organic carbon produces greater
      confidence. Bayesian statistics, therefore, provide guidance for the planning and
      operation of organic carbon detection activities on Mars. Suggestions for future
      organic carbon detection missions and instruments are as follows: (i) On Earth,
      instruments should be tested with analog samples of known organic content to
      determine their true positive to false positive ratios. (ii) On the mission, for
      an instrument with a true positive to false positive ratio above one, it should
      be recognized that each positive detection of organic carbon will result in a
      progressive increase in the probability of indigenous organic carbon being
      present; repeated measurements, therefore, can overcome some of the deficiencies
      of a less-than-definitive test. (iii) For a fixed number of analyses, the highest
      true positive to false positive ratio method or instrument will provide the
      greatest probability that indigenous organic carbon is present. (iv) On Mars,
      analyses should concentrate on samples with highest prior probability of
      indigenous organic carbon; intuitive desires to contrast samples of high prior
      probability and low prior probability of indigenous organic carbon should be
      resisted.

PMID- 25061907
TI  - Latest developments in TEVAR.

PMID- 25061906
TI  - Independent origin of plasmodium falciparum antifolate super-resistance, Uganda,
      Tanzania, and Ethiopia.
AB  - Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine
      pyrimethamine in intermittent preventive treatment for malaria during pregnancy.
      It is characterized by the A581G Pfdhps mutation on a background of the double
      mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004
      2008, we investigated the evolutionary origin of the A581G mutation by
      characterizing microsatellite diversity flanking Pfdhps triple-mutant
      (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with
      double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles
      derived from 1 lineage that was distinct from those in Uganda and Tanzania.
      Uganda and Tanzania triple mutants derived from the previously characterized
      southeastern Africa double-mutant lineage. The A581G mutation has occurred
      multiple times on local Pfdhps double-mutant backgrounds; however, a novel
      microsatellite allele incorporated into the Tanzania lineage since 2004
      illustrates the local expansion of emergent triple-mutant lineages. 

PMID- 25061908
TI  - Iatrogenic iliac rupture and acute limb ischemia during recanalization of
      bilateral iliac axis occlusion (TASC D).

PMID- 25061909
TI  - Severe encephalitis caused by Toscana virus, Greece.

PMID- 25061910
TI  - Impact of (18)F-FDG PET/CT on the staging and management of follicular lymphoma.
AB  - Follicular lymphoma (FL) is the most common indolent lymphoma. Despite the
      evidence-based utilization of fluorine-18 fludeoxyglucose positron emission
      tomography ((18)F-FDG PET)/CT in aggressive lymphomas, the utility of PET in FL
      remains controversial and varies across different jurisdictions. The management
      of patients with FL differs from aggressive lymphomas and is usually reserved for
      patients with localized disease in whom long-term control may potentially be
      achieved by involved field radiotherapy, or for symptomatic patients with
      advanced-stage disease in whom systemic therapy is indicated. There is a growing
      body of literature supporting the use of PET/CT in initial staging of FL to guide
      management decisions. In this review, we summarize the existing literature and
      present cases from our experience to illustrate current knowledge on the
      potential role of (18)F-FDG PET/CT in FL. 

PMID- 25061911
TI  - Unusual reaction behavior of gem-difluorocyclopropane derivatives:
      stereoselective synthesis of beta-monofluoroallylic alcohols, ethers, esters, and
      amide.
AB  - On treating gem-difluorocyclopropylstannanes, derived from the radical
      hydrostannation of gem-difluorocyclopropenes, with 1.5 equiv of MeLi in THF at 
      78  degrees C for 5 min, followed by quenching the reaction with various agents,
      such as H2O, alcohols, carboxylic acids, and tosylamide, the corresponding beta
      fluoroallylic alcohols, ethers, esters, and amide were obtained with exclusive Z
      selectivity in acceptable yields. 

PMID- 25061912
TI  - Controlling the pirouetting motion in rotaxanes by counterion exchange.
AB  - A fine control of the pirouetting motion of rotaxanes was achieved by using a
      series of metallabisdicarbollides. The latter were used as anions in the
      protonated form of benzylic amide macrocycle-containing fumaramide rotaxanes. The
      present paper discusses the synthesis and the structural and dynamic
      characterizations of the first examples of anionic boron cluster-containing
      rotaxanes. To study the dynamic properties of such molecules, the pirouetting
      rate of the weakly coordinating boron cluster-containing rotaxanes with the more
      strongly coordinating trifluoroacetate anion (TFA(-)), which would form a close
      ion pair with the macrocycle, was measured using the exchange spectroscopy NMR
      technique. Our hypothesis was that the stronger the ion pair the lower the rate
      of rotation due to the presence of a bigger volume of solvent to be moved. The
      anion would act as an anchor for the pirouetting motion. Indeed, the results show
      the expected trend: the rotaxane with the closely coordinating TFA(-) anion
      pirouettes most slowly, and the most weakly coordinating hexabromoderivative of
      cobaltabisdicarbollide pirouettes the fastest. 

PMID- 25061913
TI  - Morphological and genetic diversity of the wood-boring Xylophaga (Mollusca,
      Bivalvia): new species and records from deep-sea Iberian canyons.
AB  - Deep-sea bivalves of the Xylophagaidae, a poorly known group, are obligate wood
      borers. Deployment of wood in three submarine canyons off the Iberian coast, the
      Blanes and La Fonera Canyons (Mediterranean Sea) and the Aviles Canyon (Cantabric
      Sea, Bay of Biscay), lead to the discovery of four xylophagaid species in our
      samples. Xylophaga dorsalis (the dominant species), X. atlantica, X. cf. anselli
      and the new species X. brava, were identified on the basis of morphological data,
      and supported by a phylogenetic reconstruction based on the nuclear genes 18S
      rDNA and 28S rDNA and including several genus of Xylophagaidae. Genetic
      divergence between species of Xylophaga varied between genes, ranging from 0.5 to
      4.0% for the 18SrDNA and from 4.1 to 16.6% for the 28SrDNA. Xylophaga brava sp.
      nov. appeared to be restricted to the Mediterranean and morphologically resembled
      the closely related X. cf. anselli from the Cantabrian Sea. However, they clearly
      diverged in two well-supported clades. Low levels of intraspecific variability
      and higher interspecific divergence between species also supported the existence
      of these two different species. Morphologically they differ in the number of
      cirri at the siphon openings, in the shape of the posterior shell and in the size
      of prodissoconch II. The new species is characterized by having weak, poorly
      mineralized mesoplax and siphons united throughout, covered by a periostracal,
      non-calcified tube; distinct proximal and distal siphons, the former translucent
      and soft, the latter muscular, with concentric rings. Xylophaga atlantica,
      previously known only from the western Atlantic, is reported for the first time
      in the Mediterranean Sea. Whether its presence in the Mediterranean indicates its
      natural distribution or reflects its recent introduction is unknown. Although
      xylophagaids have been previously reported to recruit heavily to wood deposited
      on the seabed, these four species colonized wood suspended 30 m above the
      seafloor. 

PMID- 25061914
TI  - Chinese herbal medicines for treating skin and soft-tissue infections.
AB  - BACKGROUND: Skin and soft-tissue infections (SSTIs) are common infections of the
      epidermis, dermis or subcutaneous tissue. SSTIs range in severity from minor,
      self-limiting, superficial infections to deep, aggressive, gangrenous, life
      threatening infections. Some classifications divide SSTIs into 'complicated' and
      'uncomplicated' infections based on clinical severity. Treatments of SSTIs
      involves antibiotic therapy, surgical debridement or drainage, and resuscitation
      if required. Sometimes these treatments are limited by high treatment costs,
      bacterial resistance to antibiotics and side effects, therefore, many people with
      SSTIs are turning to Chinese herbal medicines to treat this problem.Chinese
      herbal medicines are natural substances that have been used for centuries in
      China where they are generally considered to be effective for SSTIs. Some Chinese
      herbal medicines have been shown to have antibacterial and anti-inflammatory
      properties, although a few herbal medicines have been reported to have side
      effects. Therefore there is a need to review the current clinical evidence
      systematically to inform current practice and guide future studies on Chinese
      herbal medicines for SSTIs. OBJECTIVES: To evaluate the benefits and harms of
      Chinese herbal medicines for treating skin and soft-tissue infections (SSTIs).
      SEARCH METHODS: Searches were not restricted by date, language or publication
      status. In July 2014 we searched the following electronic databases: the Cochrane
      Wounds Group Specialised Register; the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process &
      Other Non-Indexed Citations); Ovid EMBASE; Ovid AMED (Allied and Complementary
      Medicine); and EBSCO CINAHL. SELECTION CRITERIA: All randomised controlled trials
      (RCTs) in people with SSTIs that compared Chinese herbal medicines with another
      intervention or control. DATA COLLECTION AND ANALYSIS: Two review authors
      screened the literature search results independently; there were no
      disagreements. MAIN RESULTS: We identified no RCTs that met the inclusion
      criteria. AUTHORS' CONCLUSIONS: There is currently no information available from
      RCTs to support or refute the use of Chinese herbal medicines in treating people
      with SSTIs.

PMID- 25061915
TI  - Oxygen-free atomic layer deposition of indium sulfide.
AB  - Atomic layer deposition (ALD) of indium sulfide (In2S3) films was achieved using
      a newly synthesized indium precursor and hydrogen sulfide. We obtain dense and
      adherent thin films free from halide and oxygen impurities. Self-limiting half
      reactions are demonstrated at temperatures up to 225  degrees C, where oriented
      crystalline thin films are obtained without further annealing. Low-temperature
      growth of 0.89 A/cycle is observed at 150  degrees C, while higher growth
      temperatures gradually reduce the per-cycle growth rate. Rutherford
      backscattering spectroscopy (RBS) together with depth-profiling Auger electron
      spectroscopy (AES) reveal a S/In ratio of 1.5 with no detectable carbon,
      nitrogen, halogen, or oxygen impurities. The resistivity of thin films prior to
      air exposure decreases with increasing deposition temperature, reaching <1
      Omega.cm for films deposited at 225  degrees C. Hall measurements reveal n-type
      conductivity due to free electron concentrations up to 10(18) cm(-3) and
      mobilities of order 1 cm(2)/(V.s). The digital synthesis of In2S3 via ALD at
      temperatures up to 225  degrees C may allow high quality thin films to be
      leveraged in optoelectronic devices including photovoltaic absorbers, buffer
      layers, and intermediate band materials. 

PMID- 25061916
TI  - Simultaneous analysis of nanoparticles and small molecules by high-performance
      liquid chromatography using a silica monolithic column.
AB  - A high-performance liquid chromatography method using a commercially available
      silica monolithic column for the simultaneous analysis of nanoparticles and small
      molecules was developed. The method uses the micrometer-sized flow-through pores
      and nanometer-sized mesopores of the monolithic column for separation: first,
      size separation of nanoparticles was performed by the micrometer-sized pores
      using the hydrodynamic mode, and then small molecules were separated by the
      nanometer-sized pores using the normal-phase mode. The method was used to
      evaluate and compare three existing methods for purifying nanoparticles and to
      analyse nanoparticle stability. The bimodal structure of the monolithic column is
      promising for the simultaneous separation of nanoparticles and small molecules. 

PMID- 25061918
TI  - Embedding covalency into metal catalysts for efficient electrochemical conversion
      of CO2.
AB  - CO2 conversion is an essential technology to develop a sustainable carbon economy
      for the present and the future. Many studies have focused extensively on the
      electrochemical conversion of CO2 into various useful chemicals. However, there
      is not yet a solution of sufficiently high enough efficiency and stability to
      demonstrate practical applicability. In this work, we use first-principles-based
      high-throughput screening to propose silver-based catalysts for efficient
      electrochemical reduction of CO2 to CO while decreasing the overpotential by 0.4
      0.5 V. We discovered the covalency-aided electrochemical reaction (CAER)
      mechanism in which p-block dopants have a major effect on the modulating reaction
      energetics by imposing partial covalency into the metal catalysts, thereby
      enhancing their catalytic activity well beyond modulations arising from d-block
      dopants. In particular, sulfur or arsenic doping can effectively minimize the
      overpotential with good structural and electrochemical stability. We expect this
      work to provide useful insights to guide the development of a feasible strategy
      to overcome the limitations of current technology for electrochemical CO2
      conversion. 

PMID- 25061917
TI  - Identification of a small molecule that increases hemoglobin oxygen affinity and
      reduces SS erythrocyte sickling.
AB  - Small molecules that increase the oxygen affinity of human hemoglobin may reduce
      sickling of red blood cells in patients with sickle cell disease. We screened
      38,700 compounds using small molecule microarrays and identified 427 molecules
      that bind to hemoglobin. We developed a high-throughput assay for evaluating the
      ability of the 427 small molecules to modulate the oxygen affinity of hemoglobin.
      We identified a novel allosteric effector of hemoglobin, di(5-(2,3-dihydro-1,4
      benzodioxin-2-yl)-4H-1,2,4-triazol-3-yl)disulfide (TD-1). TD-1 induced a greater
      increase in oxygen affinity of human hemoglobin in solution and in red blood
      cells than did 5-hydroxymethyl-2-furfural (5-HMF), N-ethylmaleimide (NEM), or
      diformamidine disulfide. The three-dimensional structure of hemoglobin complexed
      with TD-1 revealed that monomeric units of TD-1 bound covalently to beta-Cys93
      and beta-Cys112, as well as noncovalently to the central water cavity of the
      hemoglobin tetramer. The binding of TD-1 to hemoglobin stabilized the relaxed
      state (R3-state) of hemoglobin. TD-1 increased the oxygen affinity of sickle
      hemoglobin and inhibited in vitro hypoxia-induced sickling of red blood cells in
      patients with sickle cell disease without causing hemolysis. Our study indicates
      that TD-1 represents a novel lead molecule for the treatment of patients with
      sickle cell disease.

PMID- 25061919
TI  - Rickettsia felis Infections and comorbid conditions, Laos, 2003-2011.

PMID- 25061920
TI  - Comparing the effects of age, BMI and gender on severe injury (AIS 3+) in motor
      vehicle crashes.
AB  - BACKGROUND: The effects of age, body mass index (BMI) and gender on motor vehicle
      crash (MVC) injuries are not well understood and current prevention efforts do
      not effectively address variability in occupant characteristics. OBJECTIVES: (1)
      Characterize the effects of age, BMI and gender on serious-to-fatal MVC injury.
      (2) Identify the crash modes and body regions where the effects of occupant
      characteristics on the numbers of occupants with injury is largest, and thereby
      aid in prioritizing the need for human surrogates that represent different types
      of occupant characteristics and adaptive restraint systems that consider these
      characteristics. METHODS: Multivariate logistic regression was used to model the
      effects of occupant characteristics (age, BMI, gender), vehicle and crash
      characteristics on serious-to-fatal injuries (AIS 3+) by body region and crash
      mode using the 2000-2010 National Automotive Sampling System (NASS-CDS) dataset.
      Logistic regression models were applied to weighted crash data to estimate the
      change in the number of annual injured occupants with AIS 3+ injury that would
      occur if occupant characteristics were limited to their 5th percentiles (age<=17
      years old, BMI<=19kg/m(2)) or male gender. RESULTS: Limiting age was associated
      with a decrease in the total number of occupants with head [8396, 95% CI 6871
      9070] and thorax injuries [17,961, 95% CI 15,960-18,859] across all crash modes,
      decreased occupants with spine [3843, 95% CI 3065-4242] and upper extremity
      [3578, 95% CI 1402-4439] injuries in frontal and rollover crashes and decreased
      abdominal [1368, 95% CI 1062-1417] and lower extremity [4584, 95% CI 4012-4995]
      injuries in frontal impacts. The age effect was modulated by gender with older
      females more likely to have thorax and upper extremity injuries than older males.
      Limiting BMI was associated with 2069 [95% CI 1107-2775] fewer thorax injuries in
      nearside crashes, and 5304 [95% CI 4279-5688] fewer lower extremity injuries in
      frontal crashes. Setting gender to male resulted in fewer occupants with head
      injuries in farside crashes [1999, 95% CI 844-2685] and fewer thorax [5618, 95%
      CI 4212-6272], upper [3804, 95% CI 1781-4803] and lower extremity [2791, 95% CI
      2216-3256] injuries in frontal crashes. Results indicate that age provides the
      greater relative contribution to injury when compared to gender and BMI,
      especially for thorax and head injuries. CONCLUSIONS: Restraint systems that
      account for the differential injury risks associated with age, BMI and gender
      could have a meaningful effect on injury in motor-vehicle crashes. Computational
      models of humans that represent older, high BMI, and female occupants are needed
      for use in simulations of particular types of crashes to develop these restraint
      systems.

PMID- 25061921
TI  - Elemental composition of particulate matter and the association with lung
      function.
AB  - BACKGROUND: Negative effects of long-term exposure to particulate matter (PM) on
      lung function have been shown repeatedly. Spatial differences in the composition
      and toxicity of PM may explain differences in observed effect sizes between
      studies. METHODS: We conducted a multicenter study in 5 European birth cohorts
      BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA
      (The Netherlands)-for which lung function measurements were available for study
      subjects at the age of 6 or 8 years. Individual annual average residential
      exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc
      within PM smaller than 2.5 MUm (PM2.5) and smaller than 10 MUm (PM10) was
      estimated using land-use regression models. Associations between air pollution
      and lung function were analyzed by linear regression within cohorts, adjusting
      for potential confounders, and then combined by random effects meta-analysis.
      RESULTS: We observed small reductions in forced expiratory volume in the first
      second, forced vital capacity, and peak expiratory flow related to exposure to
      most elemental pollutants, with the most substantial negative associations found
      for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases
      in forced expiratory volume in the first second of 1.6% (95% confidence interval
      = 0.4% to 2.7%) and 2.3% (-0.1% to 4.6%) per increase in exposure of 2 and 200
      ng/m, respectively. Associations remained after adjusting for PM mass. However,
      associations with these elements were not evident in all cohorts, and
      heterogeneity of associations with exposure to various components was larger than
      for exposure to PM mass. CONCLUSIONS: Although we detected small adverse effects
      on lung function associated with annual average levels of some of the evaluated
      elements (particularly nickel and sulfur), lower lung function was more
      consistently associated with increased PM mass.

PMID- 25061922
TI  - Regression discontinuity designs in epidemiology: causal inference without
      randomized trials.
AB  - When patients receive an intervention based on whether they score below or above
      some threshold value on a continuously measured random variable, the intervention
      will be randomly assigned for patients close to the threshold. The regression
      discontinuity design exploits this fact to estimate causal treatment effects. In
      spite of its recent proliferation in economics, the regression discontinuity
      design has not been widely adopted in epidemiology. We describe regression
      discontinuity, its implementation, and the assumptions required for causal
      inference. We show that regression discontinuity is generalizable to the survival
      and nonlinear models that are mainstays of epidemiologic analysis. We then
      present an application of regression discontinuity to the much-debated
      epidemiologic question of when to start HIV patients on antiretroviral therapy.
      Using data from a large South African cohort (2007-2011), we estimate the causal
      effect of early versus deferred treatment eligibility on mortality. Patients
      whose first CD4 count was just below the 200 cells/MUL CD4 count threshold had a
      35% lower hazard of death (hazard ratio = 0.65 [95% confidence interval = 0.45
      0.94]) than patients presenting with CD4 counts just above the threshold. We
      close by discussing the strengths and limitations of regression discontinuity
      designs for epidemiology. 

PMID- 25061923
TI  - Prenatal exposure to phenols and growth in boys.
AB  - BACKGROUND: Phenols interact with nuclear receptors implicated in growth and
      adipogenesis regulation. Only a few studies have explored their effects on growth
      in humans. OBJECTIVES: We studied the associations of maternal exposure to
      phenols during pregnancy with prenatal and postnatal growth of male newborns.
      METHODS: Within a cohort of women recruited during pregnancy, we selected 520
      mother-son pairs and quantified 9 phenols in spot urine samples collected during
      pregnancy. We used ultrasonography during pregnancy, together with birth
      measurements, to assess fetal growth. We modeled individual postnatal growth
      trajectories from repeated measures of weight and height in the first 3 years of
      life. RESULTS: Triclosan concentration was negatively associated with growth
      parameters measured at the third ultrasound examination but not earlier in
      pregnancy. At birth, this phenol tended to be negatively associated with head
      circumference (-1.2 mm for an interquartile range [IQR] increase in ln
      transformed triclosan concentration [95% confidence interval = -2.6 to 0.3]) but
      not with weight or height. Parabens were positively associated with weight at
      birth. This positive association remained for 3 years for methylparaben (beta =
      193 g [-4 to 389]) for an IQR increase in ln-transformed concentrations.
      CONCLUSION: We relied on only 1 spot urine sample to assess exposure; because of
      the high variability in phenol urinary concentrations reported during pregnancy,
      using only 1 sample may result in exposure misclassification, in particular for
      bisphenol A. Our study suggested associations between prenatal exposure to
      parabens and triclosan and prenatal or early postnatal growth.

PMID- 25061924
TI  - Light at night and breast cancer risk among California teachers.
AB  - BACKGROUND: There is convincing evidence that circadian disruption mediated by
      exposure to light at night promotes mammary carcinogenesis in rodents. The role
      that light at night plays in human breast cancer etiology remains unknown. We
      evaluated the relationship between estimates of indoor and outdoor light at night
      and the risk of breast cancer among members of the California Teachers Study.
      METHODS: Indoor light-at-night estimates were based on questionnaire data
      regarding sleep habits and use of nighttime lighting while sleeping. Estimates of
      outdoor light at night were derived from imagery data obtained from the US
      Defense Meteorological Satellite Program assigned to geocoded addresses of study
      participants. Analyses were conducted among 106,731 California Teachers Study
      members who lived in California, had no prior history of breast cancer, and
      provided information on lighting while sleeping. Five thousand ninety-five cases
      of invasive breast cancer diagnosed 1995-2010 were identified via linkage to the
      California Cancer Registry. We used age-stratified Cox proportional hazard models
      to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting
      for breast cancer risk factors and neighborhood urbanization and socioeconomic
      class. RESULTS: An increased risk was found for women living in areas with the
      highest quintile of outdoor light-at-night exposure estimates (HR = 1.12 [95% CI
      = 1.00-1.26]; test for trend, P = 0.06). Although more pronounced among
      premenopausal women (HR = 1.34 [95% CI = 1.07-1.69]; test for trend, P = 0.04),
      the associations did not differ statistically by menopausal status (test for
      interaction, P = 0.34). CONCLUSIONS: Women living in areas with high levels of
      ambient light at night may be at an increased risk of breast cancer. Future
      studies that integrate quantitative measurements of indoor and outdoor light at
      night are warranted.

PMID- 25061926
TI  - Prior experience biases subcortical sensitivity to sound patterns.
AB  - To make sense of our ever-changing world, our brains search out patterns. This
      drive can be so strong that the brain imposes patterns when there are none. The
      opposite can also occur: The brain can overlook patterns because they do not
      conform to expectations. In this study, we examined this neural sensitivity to
      patterns within the auditory brainstem, an evolutionarily ancient part of the
      brain that can be fine-tuned by experience and is integral to an array of
      cognitive functions. We have recently shown that this auditory hub is sensitive
      to patterns embedded within a novel sound stream, and we established a link
      between neural sensitivity and behavioral indices of learning [Skoe, E., Krizman,
      J., Spitzer, E., & Kraus, N. The auditory brainstem is a barometer of rapid
      auditory learning. Neuroscience, 243, 104-114, 2013]. We now ask whether this
      sensitivity to stimulus statistics is biased by prior experience and the
      expectations arising from this experience. To address this question, we recorded
      complex auditory brainstem responses (cABRs) to two patterned sound sequences
      formed from a set of eight repeating tones. For both patterned sequences, the
      eight tones were presented such that the transitional probability (TP) between
      neighboring tones was either 33% (low predictability) or 100% (high
      predictability). Although both sequences were novel to the healthy young adult
      listener and had similar TP distributions, one was perceived to be more musical
      than the other. For the more musical sequence, participants performed above
      chance when tested on their recognition of the most predictable two-tone
      combinations within the sequence (TP of 100%); in this case, the cABR differed
      from a baseline condition where the sound sequence had no predictable structure.
      In contrast, for the less musical sequence, learning was at chance, suggesting
      that listeners were "deaf" to the highly predictable repeating two-tone
      combinations in the sequence. For this condition, the cABR also did not differ
      from baseline. From this, we posit that the brainstem acts as a Bayesian sound
      processor, such that it factors in prior knowledge about the environment to index
      the probability of particular events within ever-changing sensory conditions. 

PMID- 25061925
TI  - Dynamics of self-monitoring and error detection in speech production: evidence
      from mental imagery and MEG.
AB  - A critical subroutine of self-monitoring during speech production is to detect
      any deviance between expected and actual auditory feedback. Here we investigated
      the associated neural dynamics using MEG recording in mental-imagery-of-speech
      paradigms. Participants covertly articulated the vowel /a/; their own
      (individually recorded) speech was played back, with parametric manipulation
      using four levels of pitch shift, crossed with four levels of onset delay. A
      nonmonotonic function was observed in early auditory responses when the onset
      delay was shorter than 100 msec: Suppression was observed for normal playback,
      but enhancement for pitch-shifted playback; however, the magnitude of enhancement
      decreased at the largest level of pitch shift that was out of pitch range for
      normal conversion, as suggested in two behavioral experiments. No difference was
      observed among different types of playback when the onset delay was longer than
      100 msec. These results suggest that the prediction suppresses the response to
      normal feedback, which mediates source monitoring. When auditory feedback does
      not match the prediction, an "error term" is generated, which underlies deviance
      detection. We argue that, based on the observed nonmonotonic function, a
      frequency window (addressing spectral difference) and a time window (constraining
      temporal difference) jointly regulate the comparison between prediction and
      feedback in speech. 

PMID- 25061927
TI  - Predicting the semantic category of internally generated words from neuromagnetic
      recordings.
AB  - In this study, we explore the possibility to predict the semantic category of
      words from brain signals in a free word generation task. Participants produced
      single words from different semantic categories in a modified semantic fluency
      task. A Bayesian logistic regression classifier was trained to predict the
      semantic category of words from single-trial MEG data. Significant classification
      accuracies were achieved using sensor-level MEG time series at the time interval
      of conceptual preparation. Semantic category prediction was also possible using
      source-reconstructed time series, based on minimum norm estimates of cortical
      activity. Brain regions that contributed most to classification on the source
      level were identified. These were the left inferior frontal gyrus, left middle
      frontal gyrus, and left posterior middle temporal gyrus. Additionally, the
      temporal dynamics of brain activity underlying the semantic preparation during
      word generation was explored. These results provide important insights about
      central aspects of language production. 

PMID- 25061928
TI  - An electrophysiological dissociation between orbitofrontal reality filtering and
      context source monitoring.
AB  - Memory influences behavior in multiple ways. One important aspect is to remember
      in what precise context in the past a piece of information was acquired (context
      source monitoring). Another important aspect is to sense whether an upcoming
      thought, composed of fragments of memories, refers to present reality and can be
      acted upon (orbitofrontal reality filtering). Whether these memory control
      processes share common underlying mechanisms is unknown. Failures of both have
      been held accountable for false memories, including confabulation.
      Electrophysiological and imaging studies suggest a dissociation but used very
      different paradigms. In this study, we juxtaposed the requirements of context
      source monitoring and reality filtering within a unique continuous recognition
      task, which healthy participants performed while high-resolution evoked
      potentials were recorded. The mechanisms dissociated both behaviorally and
      electrophysiologically: Reality filtering induced a frontal positivity, absence
      of a specific electrocortical configuration, and posterior medial orbitofrontal
      activity at 200-300 msec. Context source monitoring had no electrophysiological
      expression in this early period. It was slower and less accurate than reality
      filtering and induced a prolonged positive potential over frontal leads starting
      at 400 msec. The study demonstrates a hitherto unrecognized separation between
      orbitofrontal reality filtering and source monitoring. Whereas deficient
      orbitofrontal reality filtering is associated with reality confusion in thinking,
      the behavioral correlates of deficient source monitoring should be verified with
      controlled experimental exploration. 

PMID- 25061929
TI  - Multisensory integration: the case of a time window of gesture-speech
      integration.
AB  - This experiment investigates the integration of gesture and speech from a
      multisensory perspective. In a disambiguation paradigm, participants were
      presented with short videos of an actress uttering sentences like "She was
      impressed by the BALL, because the GAME/DANCE...." The ambiguous noun (BALL) was
      accompanied by an iconic gesture fragment containing information to disambiguate
      the noun toward its dominant or subordinate meaning. We used four different
      temporal alignments between noun and gesture fragment: the identification point
      (IP) of the noun was either prior to (+120 msec), synchronous with (0 msec), or
      lagging behind the end of the gesture fragment (-200 and -600 msec). ERPs
      triggered to the IP of the noun showed significant differences for the
      integration of dominant and subordinate gesture fragments in the -200, 0, and
      +120 msec conditions. The outcome of this integration was revealed at the target
      words. These data suggest a time window for direct semantic gesture-speech
      integration ranging from at least -200 up to +120 msec. Although the -600 msec
      condition did not show any signs of direct integration at the homonym,
      significant disambiguation was found at the target word. An explorative analysis
      suggested that gesture information was directly integrated at the verb,
      indicating that there are multiple positions in a sentence where direct gesture
      speech integration takes place. Ultimately, this would implicate that in natural
      communication, where a gesture lasts for some time, several aspects of that
      gesture will have their specific and possibly distinct impact on different
      positions in an utterance.

PMID- 25061930
TI  - Rehearsing biological motion in working memory: an EEG study.
AB  - Holding biological motion (BM), the movements of animate entities, in working
      memory (WM) is important to our daily social life. However, how BM is maintained
      in WM remains unknown. The current study investigated this issue and hypothesized
      that, analogous to BM perception, the human mirror neuron system (MNS) is
      involved in rehearsing BM in WM. To examine the MNS hypothesis of BM rehearsal,
      we used an EEG index of mu suppression (8-12 Hz), which has been linked to the
      MNS. Using a change detection task, we manipulated the BM memory load in three
      experiments. We predicted that mu suppression in the maintenance phase of WM
      would be modulated by the BM memory load; moreover, a negative correlation
      between the number of BM stimuli in WM and the degree of mu suppression may
      emerge. The results of Experiment 1 were in line with our predictions and
      revealed that mu suppression increased as the memory load increased from two to
      four BM stimuli; however, mu suppression then plateaued, as WM could only hold,
      at most, four BM stimuli. Moreover, the predicted negative correlation was
      observed. Corroborating the findings of Experiment 1, Experiment 2 further
      demonstrated that once participants used verbal codes to process the motion
      information, the mu suppression or modulation by memory load vanished. Finally,
      Experiment 3 demonstrated that the findings in Experiment 1 were not limited to
      one specific type of stimuli. Together, these results provide evidence that the
      MNS underlies the process of rehearsing BM in WM. 

PMID- 25061931
TI  - Autobiographically significant concepts: more episodic than semantic in nature?
      An electrophysiological investigation of overlapping types of memory.
AB  - A common assertion is that semantic memory emerges from episodic memory, shedding
      the distinctive contexts associated with episodes over time and/or repeated
      instances. Some semantic concepts, however, may retain their episodic origins or
      acquire episodic information during life experiences. The current study examined
      this hypothesis by investigating the ERP correlates of autobiographically
      significant (AS) concepts, that is, semantic concepts that are associated with
      vivid episodic memories. We inferred the contribution of semantic and episodic
      memory to AS concepts using the amplitudes of the N400 and late positive
      component, respectively. We compared famous names that easily brought to mind
      episodic memories (high AS names) against equally famous names that did not bring
      such recollections to mind (low AS names) on a semantic task (fame judgment) and
      an episodic task (recognition memory). Compared with low AS names, high AS names
      were associated with increased amplitude of the late positive component in both
      tasks. Moreover, in the recognition task, this effect of AS was highly correlated
      with recognition confidence. In contrast, the N400 component did not
      differentiate the high versus low AS names but, instead, was related to the
      amount of general knowledge participants had regarding each name. These results
      suggest that semantic concepts high in AS, such as famous names, have an episodic
      component and are associated with similar brain processes to those that are
      engaged by episodic memory. Studying AS concepts may provide unique insights into
      how episodic and semantic memory interact. 

PMID- 25061932
TI  - Predictors of consistent condom use among Chinese female sex workers: an
      application of the protection motivation theory.
AB  - We utilized Protection Motivation Theory to assess predictors of intention and
      behavior of consistent condom use among Chinese female sex workers (FSWs). A self
      administered questionnaire was used in a cross-sectional survey among 700 FSWs in
      Guangxi, China. Multivariate logistic regression analysis indicated that
      extrinsic and intrinsic rewards, self-efficacy, and response costs predicted
      consistent condom use intention and behavior among FSWs. Sexually transmitted
      infection/ HIV prevention programs need to reduce FSWs' perceptions of positive
      extrinsic rewards and intrinsic rewards for engaging in consistent condom use,
      reduce FSWs' perception of response costs for using a condom, and increase condom
      use self-efficacy among FSWs. 

PMID- 25061933
TI  - Leptospira and leptospirosis in China.
AB  - PURPOSE OF REVIEW: In this review, we introduce the epidemiological features,
      clinical types, laboratory diagnosis, and routine surveillance of leptospirosis
      in China. RECENT FINDINGS: Leptospirosis has been prevalent sporadically in China
      in recent years, but its incidence has decreased, probably due to the lower
      leptospire-carrying rate in pigs. Leptospira interrogans serogroup
      Icterohaemorrhagiae serovar Lai is the most common pathogen in Chinese
      leptospirosis patients and Apodemus agrarius is its major animal host. At least
      75% of Chinese leptospirosis patients suffer from the mild influenza-like type of
      leptospirosis that is caused by any serovars of L. interrogans. However,
      leptospirosis patients with the pulmonary diffuse hemorrhagic type have a high
      mortality (40-60%). L. interrogans serovar Lai is the causative agent in 75% of
      the pulmonary diffuse hemorrhagic leptospirosis patients. Several outer membrane
      protein antigens exist in all the L. interrogans serovars prevailing in China and
      predominant T- and B-cell combined epitopes in the outer membrane protein
      antigens have been identified that can be used for developing novel universal
      leptospirosis vaccines. SUMMARY: Leptospirosis cases in the Chinese population
      have gradually decreased in recent years, but it is still an important zoonotic
      infectious disease. The development of universal vaccines is critical for the
      prevention and control of leptospirosis.

PMID- 25061934
TI  - Does land-use intensification decrease plant phylogenetic diversity in local
      grasslands?
AB  - Phylogenetic diversity (PD) has been successfully used as a complement to
      classical measures of biological diversity such as species richness or functional
      diversity. By considering the phylogenetic history of species, PD broadly
      summarizes the trait space within a community. This covers amongst others complex
      physiological or biochemical traits that are often not considered in estimates of
      functional diversity, but may be important for the understanding of community
      assembly and the relationship between diversity and ecosystem functions. In this
      study we analyzed the relationship between PD of plant communities and land-use
      intensification in 150 local grassland plots in three regions in Germany.
      Specifically we asked whether PD decreases with land-use intensification and if
      so, whether the relationship is robust across different regions. Overall, we
      found that species richness decreased along land-use gradients the results
      however differed for common and rare species assemblages. PD only weakly
      decreased with increasing land-use intensity. The strength of the relationship
      thereby varied among regions and PD metrics used. From our results we suggest
      that there is no general relationship between PD and land-use intensification
      probably due to lack of phylogenetic conservatism in land-use sensitive traits.
      Nevertheless, we suggest that depending on specific regional idiosyncrasies the
      consideration of PD as a complement to other measures of diversity can be useful.

PMID- 25061935
TI  - Effects of high pressure homogenization on the activity, stability, kinetics and
      three-dimensional conformation of a glucose oxidase produced by Aspergillus
      niger.
AB  - High pressure homogenization (HPH) is a non-thermal method, which has been
      employed to change the activity and stability of biotechnologically relevant
      enzymes. This work investigated how HPH affects the structural and functional
      characteristics of a glucose oxidase (GO) from Aspergillus niger. The enzyme was
      homogenized at 75 and 150 MPa and the effects were evaluated with respect to the
      enzyme activity, stability, kinetic parameters and molecular structure. The
      enzyme showed a pH-dependent response to the HPH treatment, with reduction or
      maintenance of activity at pH 4.5-6.0 and a remarkable activity increase (30
      300%) at pH 6.5 in all tested temperatures (15, 50 and 75 degrees C). The enzyme
      thermal tolerance was reduced due to HPH treatment and the storage for 24 h at
      high temperatures (50 and 75 degrees C) also caused a reduction of activity.
      Interestingly, at lower temperatures (15 degrees C) the activity levels were
      slightly higher than that observed for native enzyme or at least maintained.
      These effects of HPH treatment on function and stability of GO were further
      investigated by spectroscopic methods. Both fluorescence and circular dichroism
      revealed conformational changes in the molecular structure of the enzyme that
      might be associated with the distinct functional and stability behavior of GO. 

PMID- 25061937
TI  - A new algorithm and problems in automatic anterior eye chamber volume
      determining.
AB  - This study investigates the problem of automatic determination of the anterior
      eye chamber volume using previously published as well as new algorithms of image
      analysis and processing proposed by the authors. A new method for determining the
      anterior eye chamber volume that provides more accurate results has been
      proposed. The entire algorithm was implemented in Matlab and C language. 60,000
      images were obtained using OCT SS-1000 CASIA and Zeiss Visante OCT. The acquired
      images of the anterior segment of the eye had a resolution of 256*1024 pixels
      with a measuring range of 8*16mm(2). The images were acquired during routine
      medical examination at the Clinical Department of Ophthalmology, District Railway
      Hospital in Katowice, Poland, and were analysed in accordance with the
      Declaration of Helsinki. The new algorithm uses edge detection, morphological
      operations, binarization and filtration. The proposed algorithm gave the anterior
      chamber surface measurement error at the level of 4.3% and the anterior chamber
      volume measurement error of 12%. For comparison, the surface measurement error of
      the tomograph software was at 6.7%. Thus the obtained results were better by
      2.4%. The proposed algorithm provides reproducible results automatically at a
      runtime of 3s per patient using a Core i7 PC computer with 8GB of RAM. 

PMID- 25061936
TI  - Increasing HIV and decreasing syphilis prevalence in a context of persistently
      high unprotected anal intercourse, six consecutive annual surveys among men who
      have sex with men in Guangzhou, China, 2008 to 2013.
AB  - INTRODUCTION: Previous studies have reported a possibly increasing HIV prevalence
      among men who have sex with men (MSM) in China. However there have been limited
      systematic analyses of existing surveillance data to learn the trend of HIV
      prevalence and factors driving the trend. The aims of this study were to examine
      the trend of HIV prevalence among MSM in Guangzhou and to explore the role of
      unprotected anal intercourse (UAI) in the trend. METHODS: Snow-ball sampling was
      applied in the subject recruitment for the annual serological and behavioral
      surveys among MSM from 2008 to 2013. Data collected in the behavioral survey
      include demographic information, HIV related sexual behavior with men and women,
      access to HIV prevention services, and symptoms of sexually transmitted
      infections. Chi-square test was used to analyze the trend of HIV prevalence.
      Multivariate logistic regression was conducted to test the factors associated
      with HIV infection. RESULTS: HIV prevalence increased significantly from 5.0% in
      2008 to 11.4% in 2013 while syphilis prevalence decreased from 17.4% to 3.3% in
      the same period. UAI rates were high and stable in every single year, ranging
      from 54.5% to 62.0%. Those who were having UAI (OR = 1.80, 95% confidence
      interval (CI): 1.26-2.58), being migrants, having more than 10 partners, and
      infected with syphilis had higher risk for HIV infection. CONCLUSIONS: HIV
      epidemic is expanding in Guangzhou. The persistently high UAI may have played a
      major role in the increasing trend of HIV prevalence. Targeted prevention program
      should be conducted among MSM who are migrants, low educational level, syphilis
      infected, or having multiple partners to encourage HIV test and change UAI
      behavior. The general high UAI calls for tailored intervention program to promote
      healthy culture and form a safe sex social norm in the MSM community.

PMID- 25061939
TI  - Multi-scale and shape constrained localized region-based active contour
      segmentation of uterine fibroid ultrasound images in HIFU therapy.
AB  - PURPOSE: To overcome the severe intensity inhomogeneity and blurry boundaries in
      HIFU (High Intensity Focused Ultrasound) ultrasound images, an accurate and
      efficient multi-scale and shape constrained localized region-based active contour
      model (MSLCV), was developed to accurately and efficiently segment the target
      region in HIFU ultrasound images of uterine fibroids. METHODS: We incorporated a
      new shape constraint into the localized region-based active contour, which
      constrained the active contour to obtain the desired, accurate segmentation,
      avoiding boundary leakage and excessive contraction. Localized region-based
      active contour modeling is suitable for ultrasound images, but it still cannot
      acquire satisfactory segmentation for HIFU ultrasound images of uterine fibroids.
      We improved the localized region-based active contour model by incorporating a
      shape constraint into region-based level set framework to increase segmentation
      accuracy. Some improvement measures were proposed to overcome the sensitivity of
      initialization, and a multi-scale segmentation method was proposed to improve
      segmentation efficiency. We also designed an adaptive localizing radius size
      selection function to acquire better segmentation results. RESULTS: Experimental
      results demonstrated that the MSLCV model was significantly more accurate and
      efficient than conventional methods. The MSLCV model has been quantitatively
      validated via experiments, obtaining an average of 0.94 for the DSC (Dice
      similarity coefficient) and 25.16 for the MSSD (mean sum of square distance).
      Moreover, by using the multi-scale segmentation method, the MSLCV model's average
      segmentation time was decreased to approximately 1/8 that of the localized region
      based active contour model (the LCV model). CONCLUSIONS: An accurate and
      efficient multi-scale and shape constrained localized region-based active contour
      model was designed for the semi-automatic segmentation of uterine fibroid
      ultrasound (UFUS) images in HIFU therapy. Compared with other methods, it
      provided more accurate and more efficient segmentation results that are very
      close to those obtained from manual segmentation by a specialist.

PMID- 25061940
TI  - Application of colloidal gas aphron suspensions produced from Sapindus mukorossi
      for arsenic removal from contaminated soil.
AB  - Colloidal gas aphron dispersions (CGAs) can be described as a system of
      microbubbles suspended homogenously in a liquid matrix. This work examines the
      performance of CGAs in comparison to surfactant solutions for washing low levels
      of arsenic from an iron rich soil. Sodium Dodecyl Sulfate (SDS) and saponin, a
      biodegradable surfactant, obtained from Sapindus mukorossi or soapnut fruit were
      used for generating CGAs and solutions for soil washing. Column washing
      experiments were performed in down-flow and up flow modes at a soil pH of 5 and 6
      using varying concentration of SDS and soapnut solutions as well as CGAs. Soapnut
      CGAs removed more than 70% arsenic while SDS CGAs removed up to 55% arsenic from
      the soil columns in the soil pH range of 5-6. CGAs and solutions showed
      comparable performances in all the cases. CGAs were more economical since it
      contains 35% of air by volume, thereby requiring less surfactant. Micellar
      solubilization and low pH of soapnut facilitated arsenic desorption from soil
      column. FT-IR analysis of effluent suggested that soapnut solution did not
      interact chemically with arsenic thereby facilitating the recovery of soapnut
      solution by precipitating the arsenic. Damage to soil was minimal arsenic
      confirmed by metal dissolution from soil surface and SEM micrograph. 

PMID- 25061941
TI  - Monitoring of sixteen fragrance allergens and two polycyclic musks in wastewater
      treatment plants by solid phase microextraction coupled to gas chromatography.
AB  - A methodology based on headspace solid phase microextraction (HS-SPME) and gas
      chromatography-mass spectrometry (GC-MS) determination was developed for the
      monitoring and evaluation of the removal efficiency of 16 common fragrance
      allergens and two polycyclic musks in wastewater treatment plants (WWTPs). An
      experimental design with a full factorial model was applied to evaluate the
      effects of the experimental parameters on the extraction (e.g., salt content,
      time and extraction temperature). After determining the optimum conditions (2.4 g
      NaCl, 45 min at 90  degrees C), an external calibration was performed and quality
      parameters of the proposed method were evaluated. Method detection limits in the
      range of 0.01-1.7 MUg L(-1) were obtained. Satisfactory inter-day precision
      values between 4% and 23% (n=5) were obtained for most compounds. The method was
      applied to the monitoring of the target analytes in samples from two WWTPs. Seven
      target compounds were detected at the primary effluent of both plants at MUg L(
      1) levels. Limonene, linalool and eugenol were quantitatively eliminated during
      the secondary treatments of both WWTPs, while lilial, benzyl salicylate,
      galaxolide, and tonalide were still detected at the effluent waters.

PMID- 25061942
TI  - Release of potassium accompanying the dissolution of rice straw phytolith.
AB  - In rice, Si assimilated from the soil solution is deposited in inter- and
      intracellular spaces throughout the leaf and stems to form silicified structures
      (so-called phytoliths). Because K is also present in significant concentrations
      in rice stems and leaves, the question arises if K is immobilized in the
      mineralized silica during the precipitation of Si. This work determined whether
      desilification of the phytolith is a factor regulating K release by implementing
      batch experiments. Solubility of Si and K of the rice straw heated at different
      temperatures were examined to identify effect of pretreatment. Analyses of
      phytoliths using SEM-EDX and X-ray tomographic microscopy in conjunction with the
      results from batch experiments revealed that K might co-exist with occluded
      organic matter inside the phytolith structure. In the kinetic experiments,
      corresponding increases of K and Si concentrations in the supernatants were
      observed which suggested that desilification of the phytolith is a main factor
      regulating K release. The extent of heat pretreatment of the rice straw is of
      significant importance with respect to dissolution of the phytolith by affecting
      organic removal and surface modification. At temperatures lower than 600  degrees
      C, corresponding increases of the soluble Si and K with heating temperature have
      been obviously observed. In contrast, the solubility of Si and K gradually
      decreased at temperatures above 600  degrees C. This work provides insights into
      factors that control release of K and Si from phytolith and a practical
      recommendation for practices of burning rice straw that may maximize subsequent
      release of Si and K for crops.

PMID- 25061943
TI  - History of metal contamination in Lake Illawarra, NSW, Australia.
AB  - Lake Illawarra has a long history of sediment contamination, particularly by
      metals, as a result of past and current industrial operations and land uses
      within the catchment. In this study, we examined the history of metal
      contamination in sediments using metal analysis and (210)Pb and (137)Cs dating.
      The distributions of copper, zinc, arsenic, selenium, cadmium and lead
      concentrations within sediment cores were in agreement with historical events in
      the lake, and indicated that metal contamination had been occurring since the
      start of industrial activities in Port Kembla in the late 1800 s. Most metal
      contamination, however, has occurred since the 1960s. Sedimentation rates were
      found to be 0.2 cm year(-1) in Griffins Bay and 0.3 cm year(-1) in the centre of
      the lake. Inputs from creeks bringing metals from Port Kembla in the northeast of
      the lake and a copper slag emplacement from a former copper refinery on the
      Windang Peninsula were the main sources of metal inputs to Lake Illawarra. The
      metals of highest concern were zinc and copper, which exceeded the Australian and
      New Zealand sediment quality guideline values at some sites. Results showed that
      while historical contamination persists, current management practices have
      resulted in reduced metal concentrations in surface sediments in the depositional
      zones in the centre of the lake.

PMID- 25061944
TI  - Metabolic therapy with Deanna Protocol supplementation delays disease progression
      and extends survival in amyotrophic lateral sclerosis (ALS) mouse model.
AB  - Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a
      neurodegenerative disorder of motor neurons causing progressive muscle weakness,
      paralysis, and eventual death from respiratory failure. There is currently no
      cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is
      associated with impaired energy metabolism, which is pathophysiologically linked
      to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol
      (DP) is a metabolic therapy that has been reported to alleviate symptoms in
      patients with ALS. In this study we hypothesized that alternative fuels in the
      form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate
      (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would
      increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS
      mice were fed standard rodent diet (SD), KD, or either diets containing a
      metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma
      aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic
      triglyceride. Assessment of ALS-like pathology was performed using a pre-defined
      criteria for neurological score, accelerated rotarod test, paw grip endurance
      test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body
      weight were also monitored. SD+DP-fed mice exhibited improved neurological score
      from age 116 to 136 days compared to control mice. KD-fed mice exhibited better
      motor performance on all motor function tests at 15 and 16 weeks of age compared
      to controls. SD+DP and KD+DP therapies significantly extended survival time of
      SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty
      three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125
      days, while only 9% of the control animals survived past that point. Targeting
      energy metabolism with metabolic therapy produces a therapeutic effect in ALS
      mice which may prolong survival and quality of life in ALS patients. 

PMID- 25061946
TI  - AtFtsH4 perturbs the mitochondrial respiratory chain complexes and auxin
      homeostasis in Arabidopsis.
AB  - Mitochondrial AtFtsH4 protease is one of four inner membrane-bound FtsH proteases
      in Arabidopsis. We found that the loss of AtFtsH4 regulates Arabidopsis
      development and architecture by mediating the peroxidase-dependent interplay
      between hydrogen peroxide (H 2O 2) and auxin homeostasis. These morphological
      changes were correlated with elevated levels of both hydrogen peroxide and
      peroxidases, which suggested that ftsh4-4 plant was related to the oxidative
      stress, and that the architecture was caused by the auxin homeostasis
      perturbation. This view was supported by the expression levels of several auxin
      signaling genes and auxin binding and transport genes were decreased
      significantly in ftsh4-4 plants. Taken together, our data published in the May
      issue of Molecular Plant suggests a link between the lack of AtFtsH4 protease,
      oxidative stress,s and auxin homeostasis to regulate plant growth and
      development. However, the detail molecular mechanisms of AtFtSH4 regulating
      oxidation stress and auxin homeostasis is unclear. Here, we present evidence that
      the high level accumulated of H 2O 2 in ftsh4-4 may correlates with the decreased
      mitochondrial respiration genes. We also showed that the decreased auxin level
      and auxin transport may caused by the inhibition of mitochondrial respiratory
      chain complexes.

PMID- 25061945
TI  - Down-regulation of complement receptors on the surface of host monocyte even as
      in vitro complement pathway blocking interferes in dengue infection.
AB  - In dengue virus (DENV) infection, complement system (CS) activation appears to
      have protective and pathogenic effects. In severe dengue fever (DF), the levels
      of DENV non-structural-1 protein and of the products of complement activation,
      including C3a, C5a and SC5b-9, are higher before vascular leakage occurs,
      supporting the hypothesis that complement activation contributes to unfavourable
      outcomes. The clinical manifestations of DF range from asymptomatic to severe and
      even fatal. Here, we aimed to characterise CS by their receptors or activation
      product, in vivo in DF patients and in vitro by DENV-2 stimulation on monocytes.
      In comparison with healthy controls, DF patients showed lower expression of CR3
      (CD11b), CR4 (CD11c) and, CD59 on monocytes. The DF patients who were high
      producers of SC5b-9 were also those that showed more pronounced bleeding or
      vascular leakage. Those findings encouraged us to investigate the role of CS in
      vitro, using monocytes isolated from healthy subjects. Prior blocking with CR3
      alone (CD11b) or CR3 (CD11b/CD18) reduced viral infection, as quantified by the
      levels of intracellular viral antigen expression and soluble DENV non-structural
      viral protein. However, we found that CR3 alone (CD11b) or CR3 (CD11b/CD18)
      blocking did not influence major histocompatibility complex presentation neither
      active caspase-1 on monocytes, thus probably ruling out inflammasome-related
      mechanisms. Although it did impair the secretion of tumour necrosis factor alpha
      and interferon alpha. Our data provide strategies of blocking CR3 (CD11b)
      pathways could have implications for the treatment of viral infection by
      antiviral-related mechanisms. 

PMID- 25061948
TI  - Radical-triplet pair interactions as probes of long-range polymer motion in
      solution.
AB  - Radical-triplet pair interactions are used to investigate the dynamics of acrylic
      polymers in dilute solution. Methyl methacrylate was randomly copolymerized with
      a small amount of an amine-containing monomer to create the polymers. The amine
      subunits were then oxidized to nitroxide moieties (stable free radicals). Using
      time-resolved electron paramagnetic resonance (TREPR) spectroscopy on the sub
      microsecond time scale, competition is observed between two deactivation
      processes of the ester side chain photoexcited triplet state: (1) Norrish I alpha
      cleavage, leading to a 21-line main chain polymeric free radical TREPR spectrum
      with emissive triplet mechanism spin polarization, and (2) spin polarization
      transfer or quenching by a nearby stable nitroxide radical, which gives a 3-line
      spectrum exhibiting emissive radical-triplet pair spin polarization. The main
      chain polymer radical signal dominates the TREPR spectrum if the probability of
      radical-triplet pair encounters is low. These competing reactions show a strong
      dependence on nitroxide incorporation (mol %), temperature, solvent, and acrylic
      polymer ester side chain structure. A comparison of steady state EPR and TREPR
      signals from inter- vs intramolecular processes clearly demonstrates the
      influence of polymer chain dynamics on the observed phenomena. 

PMID- 25061947
TI  - Influenza virus-glycan interactions.
AB  - It has been known for many years that influenza viruses bind by their
      hemagglutinin surface glycoprotein to sialic acid (N-acetylneuraminic acid) on
      the surface of the host cell, and that avian viruses most commonly bind to sialic
      acid linked alpha2-3 to galactose while most human viruses bind to sialic acid in
      the alpha2-6 configuration. Over the past few years there has been a large
      increase in data on this binding due to technological advances in glycan binding
      assays, reverse genetic systems for influenza and in X-ray crystallography. The
      results show some surprising changes in binding specificity that do not appear to
      affect the ability of the virus to infect host cells. 

PMID- 25061950
TI  - Location matters: trends in inequalities in child mortality in Indonesia.
      Evidence from repeated cross-sectional surveys.
AB  - BACKGROUND: Considerable improvements in life expectancy and other human
      development indicators in Indonesia are thought to mask considerable disparities
      between populations in the country. We examine the existence and extent of these
      disparities by measuring trends and inequalities in the under-five mortality rate
      and neonatal mortality rate across wealth, education and geography. METHODOLOGY:
      Using data from seven waves of the Indonesian Demographic and Health Surveys,
      direct estimates of under-five and neonatal mortality rates were generated for
      1980-2011. Absolute and relative inequalities were measured by rate differences
      and ratios, and where possible, slope and relative indices of inequality.
      Disparities were assessed by levels of rural/urban location, island groups,
      maternal education and household wealth. FINDINGS: Declines in national rates of
      under-five and neonatal mortality have accorded with reductions of absolute
      inequalities in clusters stratified by wealth, maternal education and rural/urban
      location. Across these groups, relative inequalities have generally stabilised,
      with possible increases with respect to mortality across wealth subpopulations.
      Both relative and absolute inequalities in rates of under-five and neonatal
      mortality stratified by island divisions have widened. CONCLUSION: Indonesia has
      made considerable gains in reducing under-five and neonatal mortality at a
      national level, with the largest reductions happening before the Asian financial
      crisis (1997-98) and decentralisation (2000). Hasty implementation of
      decentralisation reforms may have contributed to a slowdown in mortality rate
      reduction thereafter. Widening inequities between the most developed provinces of
      Java-Bali and those of other island groupings should be of particular concern for
      a country embarking on an ambitious plan for universal health coverage by 2019. A
      focus on addressing the key supply side barriers to accessing health care and on
      the social determinants of health in remote and disadvantaged regions will be
      essential for this plan to be realised.

PMID- 25061949
TI  - Effects of methamphetamine administration on information gathering during
      probabilistic reasoning in healthy humans.
AB  - Jumping to conclusions (JTC) during probabilistic reasoning is a cognitive bias
      repeatedly demonstrated in people with schizophrenia and shown to be associated
      with delusions. Little is known about the neurochemical basis of probabilistic
      reasoning. We tested the hypothesis that catecholamines influence data gathering
      and probabilistic reasoning by administering intravenous methamphetamine, which
      is known to cause synaptic release of the catecholamines noradrenaline and
      dopamine, to healthy humans whilst they undertook a probabilistic inference task.
      Our study used a randomised, double-blind, cross-over design. Seventeen healthy
      volunteers on three visits were administered either placebo or methamphetamine or
      methamphetamine preceded by amisulpride. In all three conditions participants
      performed the "beads" task in which participants decide how much information to
      gather before making a probabilistic inference, and which measures the cognitive
      bias towards jumping to conclusions. Psychotic symptoms triggered by
      methamphetamine were assessed using Comprehensive Assessment of At-Risk Mental
      States (CAARMS). Methamphetamine induced mild psychotic symptoms, but there was
      no effect of drug administration on the number of draws to decision (DTD) on the
      beads task. DTD was a stable trait that was highly correlated within subjects
      across visits (intra-class correlation coefficients of 0.86 and 0.91 on two
      versions of the task). The less information was sampled in the placebo condition,
      the more psychotic-like symptoms the person had after the methamphetamine plus
      amisulpride condition (p = 0.028). Our results suggest that information gathering
      during probabilistic reasoning is a stable trait, not easily modified by
      dopaminergic or noradrenergic modulation. 

PMID- 25061951
TI  - Student evaluations of teaching tools: a qualitative examination of student
      perceptions.
AB  - Student evaluations of teaching (SET) are common and controversial, yet there is
      limited understanding of student perceptions of these evaluation tools. The
      authors examined an evidence-based SET tool for content validity using BSN, RN-to
      BSN, and MSN student focus groups to explore individual question items and
      identify themes. Through communication and relationships with students, SET can
      influence teaching effectiveness and student learning, although student
      perceptions of individual items vary greatly. 

PMID- 25061952
TI  - Comparison of 1 long versus 2 shorter clinical days on clinical learning outcomes
      of nursing students.
AB  - Clinical practice experiences for nursing students may be scheduled as 1 long
      day, 2 shorter days, and many other variations. Which schedule is most effective
      for learning has not been studied. This research compared competency achievement
      of students (n = 146) randomly assigned to 1 long clinical day (12 hours) with
      those in 2 shorter days (7-8 hours each). Study results found no difference in
      learning outcomes between the 2 groups. 

PMID- 25061953
TI  - Using a multidimensional approach to improve quality related to students' hand
      hygiene practice.
AB  - When faced with a hand hygiene compliance rate of 44% of nursing students in
      clinical courses, faculty took on the challenge of meeting the hospital's
      expectation of 90% compliance or greater. A multidimensional approach to improve
      students' hand hygiene compliance was used to implement interventions in the
      school's simulation center and to create supports in the clinical area. This
      approach showed positive, sustainable improvement. 

PMID- 25061954
TI  - A content analysis of visual cancer information: prevalence and use of
      photographs and illustrations in printed health materials.
AB  - Researchers and practitioners have an increasing interest in visual components of
      health information and health communication messages. This study contributes to
      this evolving body of research by providing an account of the visual images and
      information featured in printed cancer communication materials. Using content
      analysis, 147 pamphlets and 858 images were examined to determine how frequently
      images are used in printed materials, what types of images are used, what
      information is conveyed visually, and whether or not current recommendations for
      the inclusion of visual content were being followed. Although visual messages
      were found to be common in printed health materials, existing recommendations
      about the inclusion of visual content were only partially followed. Results are
      discussed in terms of how relevant theoretical frameworks in the areas of
      behavior change and visual persuasion seem to be used in these materials, as well
      as how more theory-oriented research is necessary in visual messaging efforts. 

PMID- 25061955
TI  - Neuropsychological performance in melancholic, atypical and undifferentiated
      major depression during depressed and remitted states: a prospective longitudinal
      study.
AB  - BACKGROUND: Considerable evidence has demonstrated that melancholic and atypical
      major depression have distinct biological correlates relative to undifferentiated
      major depression, but few studies have specifically delineated neuropsychological
      performance for them. METHOD: In a six-week prospective longitudinal study, we
      simultaneously compared neuropsychological performance among melancholic
      depression (n=142), atypical depression (n=76), undifferentiated major depression
      (n=91), and healthy controls (n=200) during a major depressive episode and a
      clinically remitted state, respectively. We administered neuropsychological tests
      assessing processing speed, attention, shifting, planning, verbal fluency, visual
      spatial memory, and verbal working memory to all participants. RESULTS: During
      the depressive state, the three subtypes displayed extensive cognitive
      impairment, except for attention, when compared with the healthy controls.
      Melancholic depression significantly differed from atypical depression in
      processing speed and verbal fluency. In the remitted state, the three subtypes
      recovered their visual spatial memory and verbal working memory functions to the
      healthy control level. The recovery of the other domains (processing speed, set
      shifting, planning, and verbal fluency), however, was different across the
      subtypes. No predictive relationship existed between neuropsychological
      performance and the treatment outcome. LIMITATIONS: The drop-out rate in the six
      week longitudinal study was relatively high. CONCLUSION: Our data provide
      preliminary evidence that during depressed states the three major depressive
      subtypes display similar cognitive deficits in some domains but differ in such
      domains as processing speed and verbal fluency. The recovery of the cognitive
      deficits following clinical remission from depression may be associated with
      subtypes of major depressive disorder.

PMID- 25061956
TI  - Can increased atmospheric CO2 levels trigger a runaway greenhouse?
AB  - Recent one-dimensional (globally averaged) climate model calculations by
      Goldblatt et al. (2013) suggest that increased atmospheric CO(2) could
      conceivably trigger a runaway greenhouse on present Earth if CO(2) concentrations
      were approximately 100 times higher than they are today. The new prediction runs
      contrary to previous calculations by Kasting and Ackerman (1986), which indicated
      that CO(2) increases could not trigger a runaway, even at Venus-like CO(2)
      concentrations. Goldblatt et al. argued that this different behavior is a
      consequence of updated absorption coefficients for H(2)O that make a runaway more
      likely. Here, we use a 1-D climate model with similar, up-to-date absorption
      coefficients, but employ a different methodology, to show that the older result
      is probably still valid, although our model nearly runs away at ~12 preindustrial
      atmospheric levels of CO(2) when we use the most alarmist assumptions possible.
      However, we argue that Earth's real climate is probably stable given more
      realistic assumptions, although 3-D climate models will be required to verify
      this result. Potential CO(2) increases from fossil fuel burning are somewhat
      smaller than this, 10-fold or less, but such increases could still cause
      sufficient warming to make much of the planet uninhabitable by humans.

PMID- 25061957
TI  - Colorectal endoscopic submucosal dissection: when and by whom?

PMID- 25061958
TI  - ERCP after bypass surgery. Which option would patients prefer?

PMID- 25061959
TI  - Reply to Fan et al.

PMID- 25061960
TI  - Can we develop self-expandable metallic stents without consideration of
      mechanical properties?

PMID- 25061961
TI  - Reply to Isayama et al.

PMID- 25061964
TI  - Sedation for gastrointestinal endoscopy.

PMID- 25061965
TI  - Global and local persistence of influenza A(H5N1) virus.
AB  - An understanding of the global migration dynamics of highly pathogenic avian
      influenza A(H5N1) virus is helpful for surveillance and disease prevention. To
      characterize the migration network of this virus, we used genetic analysis, which
      supported a global persistence model in which each of 9 regions acts to some
      extent as a source. Siberia is the major hub for the dispersal of the virus.
      Southeast Asia and Africa are major sources of genetically and antigenically
      novel strains. We found evidence of local persistence of the virus in Southeast
      Asia and Africa, which is rare for human influenza A viruses. The differences in
      migration dynamics between avian and human influenza viruses might help with the
      design of region-specific surveillance efforts and the selection of vaccine
      candidates. 

PMID- 25061966
TI  - Vascular endothelial growth factor A improves quality of matured porcine oocytes
      and developing parthenotes.
AB  - Vascular endothelial growth factor is a multipotent angiogenic factor implicated
      in cell survival and proliferation. The objective was to determine effects of
      exogenous recombinant human VEGFA (or VEGFA165) in culture media on porcine
      oocyte maturation and parthenote development. Adding 5 ng/mL VEGFA to the culture
      medium improved the maturation rate of denuded oocytes (P < 0.05), although 5,
      50, or 500 ng/mL did not significantly affect nuclear maturation of oocytes.
      Parthenotes from oocytes cultured either in in vitro maturation or in vitro
      culture medium supplemented with 5 or 50 ng/mL VEGFA had an improved blastocyst
      rate and increased total numbers of cells (P < 0.05). Moreover, those treated
      with 5 ng/mL of VEGFA had a higher hatched blastocyst rate (average of 121 cells
      per blastocyst). All VEGFA-treated oocytes had reduced apoptotic indices (P <
      0.05), except for those with a higher dose (500 ng/mL) of VEGFA which had more
      apoptotic cells (P < 0.05). Adding 5 ng/mL VEGFA to oocytes during the last 22 h
      of in vitro maturation improved (P < 0.05) blastocyst rates and total numbers of
      cells, with reduced apoptosis indices similar to that of long-term (44 h)
      culture. Furthermore, Axitinib (VEGFR inhibitor) reversed the effects of VEGFA on
      parthenote development (P < 0.05). Follicular fluids from medium (2-6 mm) to
      large (>6 mm) follicles contained 5.3 and 7.0 ng/mL vascular endothelial growth
      factor protein, respectively, higher (P < 0.05) than concentrations in small (<2
      mm) follicles (0.4 ng/mL). Also, VEGFA and its receptor (VEGFR-2) were detected
      (immunohistochemistry) in growing follicles and developing blastocysts. In
      addition, VEGFA inhibited caspase-3 activation in matured oocytes (P < 0.05). In
      conclusion, this is apparently the first report that VEGFA has proliferative and
      cytoprotective roles in maturing porcine oocytes and parthenotes. Furthermore, an
      optimal VEGFA concentration promoted porcine oocyte maturation and subsequent
      development. 

PMID- 25061967
TI  - Appearances can be deceptive: revealing a hidden viral infection with deep
      sequencing in a plant quarantine context.
AB  - Comprehensive inventories of plant viral diversity are essential for effective
      quarantine and sanitation efforts. The safety of regulated plant material
      exchanges presently relies heavily on techniques such as PCR or nucleic acid
      hybridisation, which are only suited to the detection and characterisation of
      specific, well characterised pathogens. Here, we demonstrate the utility of
      sequence-independent next generation sequencing (NGS) of both virus-derived small
      interfering RNAs (siRNAs) and virion-associated nucleic acids (VANA) for the
      detailed identification and characterisation of viruses infecting two quarantined
      sugarcane plants. Both plants originated from Egypt and were known to be infected
      with Sugarcane streak Egypt Virus (SSEV; Genus Mastrevirus, Family
      Geminiviridae), but were revealed by the NGS approaches to also be infected by a
      second highly divergent mastrevirus, here named Sugarcane white streak Virus
      (SWSV). This novel virus had escaped detection by all routine quarantine
      detection assays and was found to also be present in sugarcane plants originating
      from Sudan. Complete SWSV genomes were cloned and sequenced from six plants and
      all were found to share >91% genome-wide identity. With the exception of two SWSV
      variants, which potentially express unusually large RepA proteins, the SWSV
      isolates display genome characteristics very typical to those of all other
      previously described mastreviruses. An analysis of virus-derived siRNAs for SWSV
      and SSEV showed them to be strongly influenced by secondary structures within
      both genomic single stranded DNA and mRNA transcripts. In addition, the
      distribution of siRNA size frequencies indicates that these mastreviruses are
      likely subject to both transcriptional and post-transcriptional gene silencing.
      Our study stresses the potential advantages of NGS-based virus metagenomic
      screening in a plant quarantine setting and indicates that such techniques could
      dramatically reduce the numbers of non-intercepted virus pathogens passing
      through plant quarantine stations. 

PMID- 25061968
TI  - Screening-level microbial risk assessment of urban water locations: a tool for
      prioritization.
AB  - People in urban areas are exposed to microbial hazards in urban waters. In this
      study, various hazards, diseases, and water systems, where different recreation
      activities take place, are compared in an integrated quantitative microbial risk
      assessment (QMRA). The event and annual probability of gastrointestinal illness
      (GI) and Legionnaires'disease (LD) were analyzed in QMRA models using selected
      literature data. Highest mean event probabilities of GI were found for playing in
      pluvial flood from a combined sewer overflow (34%), swimming (18%), and rowing
      (13%) in the river, swimming (8.7%) and rowing (4.5%) in the lake, and playing in
      a water playground (3.7%) and in the pluvial flood from stormwater sewers (4.7%).
      At these locations, the GI probability was above the EU Bathing Water Directive
      threshold for excellent water quality (3%). All the annual risk medians were
      below the national incidence of legionellosis of 0.002%. The illness probability
      was most sensitive to the pathogens concentration (particularly Campylobacter,
      Norovirus, and Legionella) and exposure frequency. Therefore, site-specific
      pathogen data collection is the best next step to strengthen the certainty of the
      risk estimates. This study created an evidence-base that was used by water
      authorities to understand the health risks and set priorities for risk
      management. 

PMID- 25061969
TI  - Bioengineered vaults: self-assembling protein shell-lipophilic core nanoparticles
      for drug delivery.
AB  - We report a novel approach to a new class of bioengineered, monodispersed, self
      assembling vault nanoparticles consisting of a protein shell exterior with a
      lipophilic core interior designed for drug and probe delivery. Recombinant vaults
      were engineered to contain a small amphipathic alpha-helix derived from the
      nonstructural protein 5A of hepatitis C virus, thereby creating within the vault
      lumen a lipophilic microenvironment into which lipophilic compounds could be
      reversibly encapsulated. Multiple types of electron microscopy showed that
      attachment of this peptide resulted in larger than expected additional mass
      internalized within the vault lumen attributable to incorporation of host lipid
      membrane constituents spanning the vault waist (>35 nm). These bioengineered
      lipophilic vaults reversibly associate with a sample set of therapeutic
      compounds, including all-trans retinoic acid, amphotericin B, and bryostatin 1,
      incorporating hundreds to thousands of drug molecules per vault nanoparticle.
      Bryostatin 1 is of particular therapeutic interest because of its ability to
      potently induce expression of latent HIV, thus representing a preclinical lead in
      efforts to eradicate HIV/AIDS. Vaults loaded with bryostatin 1 released free
      drug, resulting in activation of HIV from provirus latency in vitro and induction
      of CD69 biomarker expression following intravenous injection into mice. The
      ability to preferentially and reversibly encapsulate lipophilic compounds into
      these novel bioengineered vault nanoparticles greatly advances their potential
      use as drug delivery systems. 

PMID- 25061970
TI  - Enzymatic synthesis of polybrominated dioxins from the marine environment.
AB  - Polyhalogenated dibenzo-p-dioxins are arguably among the most toxic molecules
      known to man. In addition to anthropogenic sources, marine invertebrates also
      harbor polybrominated dibenzo-p-dioxins of as yet unknown biogenic origin. Here,
      we report that the bmp gene locus in marine bacteria, a recently characterized
      source of polybrominated diphenyl ethers, can also synthesize dibenzo-p-dioxins
      by employing different phenolic initiator molecules. Our findings also diversify
      the structural classes of diphenyl ethers accessed by the bmp biosynthetic
      pathway. This report lays the biochemical foundation of a likely biogenetic
      origin of dibenzo-p-dioxins present in the marine metabolome and greatly expands
      the toxicity potential of marine derived polyhaloganated natural products. 

PMID- 25061973
TI  - Facile enzymatic synthesis of base J-containing oligodeoxyribonucleotides and an
      analysis of the impact of base J on DNA replication in cells.
AB  - We reported here the use of T4 bacteriophage beta-glucosyltransferase (T4 beta
      GT) for the facile synthesis of base J-containing oligodeoxyribonucleotides
      (ODNs). We found that the enzyme could catalyze the glucosylation of 5
      hydroxymethyl-2-deoxyuridine (5hmU) in both single- and double-stranded ODNs,
      though the latter reaction occurred only when 5hmU was mispaired with a guanine.
      In addition, base J blocked moderately DNA replication, but it did not induce
      mutations during replication in human cells. 

PMID- 25061974
TI  - Comparing vibrational spectra of free bumetanide and its solutions.
AB  - Bumetanide, which is known as a potent diuretic, is currently under investigation
      for its potential anti-epileptic effects in neonatal seizures. The purpose of
      this study was to examine the molecular structure of bumetanide both in the free
      form and its solutions via vibrational spectra (FT-IR, FT-Raman spectroscopies)
      and quantum chemical calculations. FT-IR and FT-Raman spectra of the title
      compound were recorded for the solid phase and the solutions of DMSO and ethanol.
      Optimized molecular geometry and vibrational wavenumbers of bumetanide were
      calculated by DFT/B3LYP functional with 6-31G(d,p), 6-31G++(d,p) and 6
      311++G(d,p) basis sets. The assignment of the vibrational modes were performed
      based on total energy distribution (TED). The same calculations were performed
      for the molecule in DMSO and ethanol solutions using the polarizable conductor
      continuum model (CPCM) method. Lastly, probable donor-acceptor interactions of
      the molecule were examined with NBO analysis in different media. In all forms of
      bumetanide (the free molecule and the other solvents), some significant changes
      were observed in the dihedral angles and the vibrational frequencies. 

PMID- 25061971
TI  - The association between serum leptin and post stroke depression: results from a
      cohort study.
AB  - BACKGROUND: Depression is a frequent mood disorder that affects around a third of
      stroke patients and has been associated with poorer outcomes. Our aim was to
      determine whether there was a relationship between inflammatory markers (leptin)
      and post-stroke depression (PSD). METHODS: One hundred and ninety-one ischemic
      stroke patients admitted to the hospital within the first 24 hours after stroke
      onset were consecutively recruited and followed up for 3 months. Enzyme-linked
      immunosorbent assay (ELISA) was used to measure serum levels of leptin at
      admission. Based on the symptoms, diagnoses of depression were made in accordance
      with DSM-IV criteria for post-stroke depression at 3 month. RESULTS: Forty-four
      patients (23.0%) were diagnosed as having major depression at 3 month. Patients
      with depression showed higher serum leptin levels at 3 month after stroke (32.2
      [IQR, 20.8-57.7] v. 9.9 [IQR, 4.6-13.1]ng/ml, respectively; P = 0.000). Serum
      levels of leptin >=20 ng/ml were independently associated with PSD [odds ratio
      (OR) 20.23, 95% confidence interval (CI) 9.11-51.26, P =  0.000], after adjusting
      for possible confounders. CONCLUSIONS: Serum leptin levels elevated at admission
      were found to be associated with PSD and may provide a new proposal for the
      treatment of PSD.

PMID- 25061975
TI  - Infection with possible precursor of avian influenza A(H7N9) virus in a child,
      China, 2013.
AB  - During the early stage of the avian influenza A(H7N9) epidemic in China in March
      2013, a strain of the virus was identified in a 4-year-old boy with mild
      influenza symptoms. Phylogenetic analysis indicated that this strain, which has
      similarity to avian subtype H9N2 viruses, may represent a precursor of more
      evolved H7N9 subtypes co-circulating among humans. 

PMID- 25061976
TI  - Phylogenetic analysis of West Nile virus genome, Iran.

PMID- 25061977
TI  - Using SCC antigen and CRP levels as prognostic biomarkers in recurrent oral
      cavity squamous cell carcinoma.
AB  - Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have
      been successfully used to stratify risk groups in primary oral squamous cell
      carcinoma (OSCC) patients; however, related biomarkers have rarely been
      investigated in recurrent OSCC. The purpose of the present study was to analyze
      the relationships of SCC-Ag and CRP levels at the time of recurrence with
      clinical factors and prognosis. We retrospectively recruited patients with
      recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One
      hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at
      the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease
      free, and at the time of recurrence. The SCC-Ag levels were significantly lowered
      after treatment (paired t-test: p = 0.001) and re-elevated at the time of
      recurrence (paired t-test: p = 0.027). An SCC-Ag level >=2.0 ng/ml and a CRP
      level >=5.0 mg/L at the time of recurrence were significantly associated with
      recurrent tumor status (P<0.001), recurrent nodal metastasis (chi2 trend test: P
      = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover,
      the influence of both elevated SCC-Ag and CRP levels on overall survival
      (P<0.001, H.R. [95% CI]: 5.406 [2.210-13.222]) still existed after adjusting for
      the recurrent tumor stage and patient age. The present study demonstrates that
      concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts
      as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant
      metastasis, and survival after the diagnosis of recurrence. This study expands
      the applicability of these two markers in the risk stratification in recurrent
      OSCC. 

PMID- 25061978
TI  - Increased arterial stiffness in resistant hypertension is associated with
      inflammatory biomarkers.
AB  - BACKGROUND: Increased levels of inflammatory biomarkers such as interleukin-6 (IL
      6), 10 (IL-10), 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) high
      sensitivity C-reactive protein (hs-CRP) are associated with arterial stiffness in
      hypertension. Indeed, resistant hypertension (RHTN) leads to unfavorable
      prognosis attributed to poor blood pressure (BP) control and target organ damage.
      This study evaluated the potential impact of inflammatory biomarkers on arterial
      stiffness in RHTN. METHODS: In this cross-sectional study, 32 RHTN, 20 mild
      hypertensive (HTN) and 20 normotensive (NT) patients were subjected to office BP
      and arterial stiffness measurements assessed by pulse wave velocity (PWV).
      Inflammatory biomarkers were measured in plasma samples. RESULTS: PWV was
      increased in RHTN compared with HTN and NT (p < 0.05). TNF-alpha levels were
      significantly higher in RHTN and HTN than NT patients. No differences in IL-6
      levels were observed. RHTN patients had a higher frequency of subjects with
      increased levels of IL-10 and IL-1beta compared with HTN and NT patients.
      Finally, IL-1beta was independently associated with PWV (p < 0.001; R(2) = 0.5;
      beta = 0.077). CONCLUSION: RHTN subjects have higher levels of inflammatory
      cytokines (TNF-alpha, IL-1beta and IL-10) as well as increased arterial
      stiffness, and detectable IL-1beta levels are associated arterial stiffness.
      These findings suggest that inflammation plays a possible role in the
      pathophysiology of RHTN.

PMID- 25061980
TI  - Alpine scree plants benefit from cryptic coloration with limited cost.
AB  - Like animals, plants are attacked by enemies (herbivores) that forage using
      visual cues; however, the defensive coloration type known as cryptic coloration
      was rarely reported in plants. For most autotrophic plants, because
      photosynthesis relies on the presence of chlorophyll, a green leaf appearance is
      standard. However, if having leaves that are not green is more beneficial than
      costly, such coloration may evolve under certain conditions. Taking advantage of
      the leaf color dimorphism of Corydalis benecincta, we showed that the cryptically
      colored leaves confer a clear benefit without obvious cost in natural
      populations. Based on this study, we try to provide a framework on which to base
      a cost-benefit analysis to investigate the evolution of cryptic leaf coloration
      in plants.

PMID- 25061979
TI  - How a replication origin and matrix attachment region accelerate gene
      amplification under replication stress in mammalian cells.
AB  - The gene amplification plays a critical role in the malignant transformation of
      mammalian cells. The most widespread method for amplifying a target gene in cell
      culture is the use of methotrexate (Mtx) treatment to amplify dihydrofolate
      reductase (Dhfr). Whereas, we found that a plasmid bearing both a mammalian
      origin of replication (initiation region; IR) and a matrix attachment region
      (MAR) was spontaneously amplified in mammalian cells. In this study, we attempted
      to uncover the underlying mechanism by which the IR/MAR sequence might accelerate
      Mtx induced Dhfr amplification. The plasmid containing the IR/MAR was
      extrachromosomally amplified, and then integrated at multiple chromosomal
      locations within individual cells, increasing the likelihood that the plasmid
      might be inserted into a chromosomal environment that permits high expression and
      further amplification. Efficient amplification of this plasmid alleviated the
      genotoxicity of Mtx. Clone-based cytogenetic and sequence analysis revealed that
      the plasmid was amplified in a chromosomal context by breakage-fusion-bridge
      cycles operating either at the plasmid repeat or at the flanking fragile site
      activated by Mtx. This mechanism explains how a circular molecule bearing IR/MAR
      sequences of chromosomal origin might be amplified under replication stress, and
      also provides insight into gene amplification in human cancer. 

PMID- 25061981
TI  - Analysis of Clonostachys rosea-induced resistance to tomato gray mold disease in
      tomato leaves.
AB  - Tomato gray mold disease, caused by Botrytis cinerea, is a serious disease in
      tomato. Clonostachys rosea is an antagonistic microorganism to B. cinerea. To
      investigate the induced resistance mechanism of C. rosea, we examined the effects
      of these microorganisms on tomato leaves, along with changes in the activities of
      three defense enzymes (PAL, PPO, GST), second messengers (NO, H2O2, O2(-)) and
      phytohormones (IAA, ABA, GA3, ZT, MeJA, SA and C2H4). Compared to the control,
      all treatments induced higher levels of PAL, PPO and GST activity in tomato
      leaves and increased NO, SA and GA3 levels. The expression of WRKY and MAPK, two
      important transcription factors in plant disease resistance, was upregulated in
      C. rosea- and C. rosea plus B. cinerea-treated samples. Two-dimensional gel
      electrophoresis analysis showed that two abundant proteins were present in the C.
      rosea plus B. cinerea-treated samples but not in the other samples. These
      proteins were determined (by mass spectrum analysis) to be LEXYL2 (beta
      xylosidase) and ATP synthase CF1 alpha subunit. Therefore, C. rosea plus B.
      cinerea treatment induces gray mold resistance in tomato. This study provides a
      basis for elucidating the mechanism of C. rosea as a biocontrol agent.

PMID- 25061983
TI  - Systems biology brings new dimensions for structure-based drug design.
AB  - In this Perspective, we focus on new, systems-centric views of structure-based
      drug design (SBDD) that we believe will impact future drug discovery research and
      development. We will first discuss new ways to identify drug targets based on
      systems intervention analysis, and then we will introduce emerging SBDD methods
      driven by advancements in systems biology. 

PMID- 25061982
TI  - Thrombin enhances NGF-mediated neurite extension via increased and sustained
      activation of p44/42 MAPK and p38 MAPK.
AB  - Rapid neurite remodeling is fundamental to nervous system development and
      plasticity. It involves neurite extension that is regulated by NGF through
      PI3K/AKT, p44/42 MAPK and p38 MAPK. It also involves neurite retraction that is
      regulated by the serine protease, thrombin. However, the intracellular signaling
      pathway by which thrombin causes neurite retraction is unknown. Using the PC12
      neuronal cell model, we demonstrate that thrombin utilizes the PI3K/AKT pathway
      for neurite retraction in NGF-differentiated cells. Interestingly, however, we
      found that thrombin enhances NGF-induced neurite extension in differentiating
      cells. This is achieved through increased and sustained activation of p44/42 MAPK
      and p38 MAPK. Thus, thrombin elicits opposing effects in differentiated and
      differentiating cells through activation of distinct signaling pathways: neurite
      retraction in differentiated cells via PI3K/AKT, and neurite extension in
      differentiating cells via p44/42 MAPK and p38 MAPK. These findings, which also
      point to a novel cooperative role between thrombin and NGF, have significant
      implications in the development of the nervous system and the disease processes
      that afflicts it as well as in the potential of combined thrombin and NGF therapy
      for impaired learning and memory, and spinal cord injury which all require
      neurite extension and remodeling. 

PMID- 25061984
TI  - Position paper on PRM and persons with long term disabilities.
AB  - In the current population we observe a rise of chronic health problems often with
      multiple characteristics. This results in a growing number of people who are
      experiencing long-term disabilities or difficulties in functioning because of
      disability. These conditions require a complex response over an extended period
      of time, that involves coordinated inputs from a wide range of health
      professionals. This paper argues the central role and benefit of rehabilitation
      and describes the rehabilitation as an integral component in the management of
      people with chronic disabilities. It also presents the most important related
      definitions: long-term care, rehabilitation for chronic disease and disability,
      the aim of physical and rehabilitation medicine (PRM). An interdisciplinary team
      is ideal for an effective implementation of rehabilitation for chronic disease
      and disability. However, the article mainly focuses on defining the role and
      contribution of the PRM physician in the rehabilitation of persons with long-term
      disabilities. The article includes: descriptions of his/her key role and
      competencies, particularly with regard to medical and functional status and
      prognosis, of the ability to comprehensively define the rehabilitation needs of
      the patient/person with respect to ICD-WHO classification domains, of the
      cooperation with other medical specialists and health professionals, of
      determining the rehabilitation potential, of developing the rehabilitation plan
      tailored to specific needs, as well as of the contribution of PRM physician in
      the follow-up care pathways. 

PMID- 25061985
TI  - Selective induction and subcellular distribution of ACONITASE 3 reveal the
      importance of cytosolic citrate metabolism during lipid mobilization in
      Arabidopsis.
AB  - Arabidopsis thaliana has three genes that encode distinct aconitases (ACO), but
      little is known about the function of each isoenzyme during plant development. In
      newly emerged seedlings of Arabidopsis, transcript and protein levels for ACO3
      were selectively induced to yield more than 80% of total aconitase activity.
      Characterization of knockout mutants for each of the three ACOs suggests a major
      role for only ACO3 in citrate metabolism. The aco3 mutant showed delayed early
      seedling growth, altered assimilation of [14C]acetate feeding and elevated
      citrate levels, which were nearly 4-fold greater than in wild-type, aco1 or aco2.
      However, both ACO1 and ACO2 are active in seedlings as shown by inhibition of
      aco3 growth by the toxin monofluoroacetate, and altered [14C]acetate assimilation
      and metabolite levels in aco1 and aco2. Relative levels of fumarate and malate
      differed between aco2 and aco3, indicating metabolically isolated pools of these
      metabolites in seedlings. Our inability to enrich ACO protein through
      mitochondria isolation, and the reduced cytosolic ACO activity of the iron-sulfur
      centre assembly mutant atm3-1, indicated a cytosolic localization of ACO3 in 3
      day-old seedlings. Subsequently, we determined that more than 90% of ACO3 was
      cytosolic. We conclude that ACO3 is cytosolic in young seedlings and functions in
      citrate catabolism consistent with the operation of the classic glyoxylate and
      not direct catabolism of citrate within mitochondria. 

PMID- 25061986
TI  - Polarity related influence maximization in signed social networks.
AB  - Influence maximization in social networks has been widely studied motivated by
      applications like spread of ideas or innovations in a network and viral marketing
      of products. Current studies focus almost exclusively on unsigned social networks
      containing only positive relationships (e.g. friend or trust) between users.
      Influence maximization in signed social networks containing both positive
      relationships and negative relationships (e.g. foe or distrust) between users is
      still a challenging problem that has not been studied. Thus, in this paper, we
      propose the polarity-related influence maximization (PRIM) problem which aims to
      find the seed node set with maximum positive influence or maximum negative
      influence in signed social networks. To address the PRIM problem, we first extend
      the standard Independent Cascade (IC) model to the signed social networks and
      propose a Polarity-related Independent Cascade (named IC-P) diffusion model. We
      prove that the influence function of the PRIM problem under the IC-P model is
      monotonic and submodular Thus, a greedy algorithm can be used to achieve an
      approximation ratio of 1-1/e for solving the PRIM problem in signed social
      networks. Experimental results on two signed social network datasets, Epinions
      and Slashdot, validate that our approximation algorithm for solving the PRIM
      problem outperforms state-of-the-art methods. 

PMID- 25061987
TI  - A metal free domino synthesis of 3-aroylindoles via two sp3 C-H activation.
AB  - A metal free synthesis of 3-aroylindole involving two sp(3) C-H activation has
      been achieved starting from o-alkynyl-N,N-dialkylamines using catalyst TBAI and
      oxidant TBHP. 

PMID- 25061988
TI  - Sulfate but not thiosulfate reduces calculated and measured urinary ionized
      calcium and supersaturation: implications for the treatment of calcium renal
      stones.
AB  - BACKGROUND: Urinary sulfate (SO4(2-)) and thiosulfate (S2O3(2-)) can potentially
      bind with calcium and decrease kidney stone risk. We modeled the effects of these
      species on the concentration of ionized calcium (iCa) and on supersaturation (SS)
      of calcium oxalate (CaOx) and calcium phosphate (CaP), and measured their in
      vitro effects on iCa and the upper limit of stability (ULM) of these salts.
      METHODS: Urine data from 4 different types of stone patients were obtained from
      the Mayo Nephrology Clinic (Model 1). A second data set was obtained from healthy
      controls and hypercalciuric stone formers in the literature who had been treated
      with sodium thiosulfate (STS) (Model 2). The Joint Expert Speciation System
      (JESS) was used to calculate iCa and SS. In Model 1, these parameters were
      calculated as a function of sulfate and thiosulfate concentrations. In Model 2,
      data from pre- and post STS urines were analyzed. ULM and iCa were determined in
      human urine as a function of sulfate and thiosulfate concentrations. RESULTS:
      Calculated iCa and SS values for all calcium salts decreased with increasing
      sulfate concentration. Thiosulfate had no effect on these parameters. In Model 2,
      calculated iCa and CaOx SS increased after STS treatment, but CaP SS decreased,
      perhaps due to a decrease in pH after STS treatment. In confirmatory in vitro
      experiments supplemental sulfate, but not thiosulfate, significantly increased
      the calcium needed to achieve the ULM of CaP and tended to increase the oxalate
      needed to reach the ULM of CaOx. Sulfate also significantly decreased iCa in
      human urine, while thiosulfate had no effect. CONCLUSION: Increasing urinary
      sulfate could theoretically reduce CaOx and CaP stone risk. Although STS may
      reduce CaP stone risk by decreasing urinary pH, it might also paradoxically
      increase iCa and CaOx SS. As such, STS may not be a viable treatment option for
      stone disease.

PMID- 25061989
TI  - Chikungunya outbreak in Bueng Kan Province, Thailand, 2013.

PMID- 25061991
TI  - Interventional management in hypertension: where do we stand?
AB  - PURPOSE OF REVIEW: Device-based interventions to lower drug-resistant
      hypertension have made the management of this disorder more complicated. In this
      review, we will focus on developments in this approach to blood pressure care
      which have appeared over the last year in a published or abstract form. RECENT
      FINDINGS: Much of the recent literature in this area is characterized by very
      large office systolic blood pressure reductions, on the order of 25 mmHg at 6
      months after intervention. However, the largest and the most rigorously conducted
      trial of renal denervation failed to meet its efficacy endpoint. We will review
      some speculations on why that may have occurred. SUMMARY: There is little
      guidance for the management of drug-resistant hypertension in existing guidelines
      due largely to an absence of clinical trials with hard cardiovascular outcomes;
      thus, most of the literature relies on short-term (generally less than 1 year)
      studies that are oriented toward efficacy (i.e., blood pressure reduction per
      se). With the failure of the Symplicity HTN3 trial to meet its efficacy endpoint,
      the entire field of renal denervation is under careful scrutiny. From this
      reviewer's perspective, this finding seems to be more of a speed-bump than a
      'road closed' sign for renal denervation, a prompt to reconsider the adequacy of
      denervation techniques and an encouragement to continue the search for robust
      predictors of clinical response.

PMID- 25061992
TI  - On the possibility of magneto-structural correlations: detailed studies of
      dinickel carboxylate complexes.
AB  - A series of water-bridged dinickel complexes of the general formula [Ni2(MU2
      OH2)(MU2-O2C(t)Bu)2(O2C(t)Bu)2(L)(L')] (L = HO2C(t)Bu, L' = HO2C(t)Bu (1),
      pyridine (2), 3-methylpyridine (4); L = L' = pyridine (3), 3-methylpyridine (5))
      has been synthesized and structurally characterized by X-ray crystallography. The
      magnetic properties have been probed by magnetometry and EPR spectroscopy, and
      detailed measurements show that the axial zero-field splitting, D, of the
      nickel(II) ions is on the same order as the isotropic exchange interaction, J,
      between the nickel sites. The isotropic exchange interaction can be related to
      the angle between the nickel centers and the bridging water molecule, while the
      magnitude of D can be related to the coordination sphere at the nickel sites. 

PMID- 25061995
TI  - Parental selection of hybrid breeding based on maternal and paternal inheritance
      of traits in rapeseed (Brassica napus L.).
AB  - Parental selection is crucial for hybrid breeding, but the methods available for
      such a selection are not very effective. In this study, a 6*6 incomplete diallel
      cross was designed using 12 rapeseed germplasms, and a total of 36 hybrids
      together with their parental lines were planted in 4 environments. Four yield
      related traits and seed oil content (OC) were evaluated. Genetic distance (GD)
      was estimated with 359 simple sequence repeats (SSRs) markers. Heterosis levels,
      general combining ability (GCA) and specific combining ability (SCA) were
      evaluated. GD was found to have a significant correlation with better-parent
      heterosis (BPH) of thousand seed weight (TSW), SCA of seeds per silique (SS),
      TSW, and seed yield per plant (SY), while SCA showed a statistically significant
      correlation with heterosis levels of all traits at 1% significance level.
      Statistically significant correlations were also observed between GCA of maternal
      or paternal parents and heterosis levels of different traits except for SS.
      Interestingly, maternal (TSW, SS, and OC) and paternal (siliques per plant (SP)
      and SY) inheritance of traits was detected using contribution ratio of maternal
      and paternal GCA variance as well as correlations between GCA and heterosis
      levels. Phenotype and heterosis levels of all the traits except TSW of hybrids
      were significantly correlated with the average performance of parents. The
      correlations between SS and SP, SP and OC, and SY and OC were statistically
      significant in hybrids but not in parents. Potential applications of parental
      selection in hybrid breeding were discussed. 

PMID- 25061996
TI  - The role of implied motion in engaging audiences for health promotion:
      encouraging naps on a college campus.
AB  - OBJECTIVE: Lack of sleep among college students negatively impacts health and
      academic outcomes. Building on research that implied motion imagery increases
      brain activity, this project tested visual design strategies to increase viewers'
      engagement with a health communication campaign promoting napping to improve
      sleep habits. PARTICIPANTS: PARTICIPANTS (N = 194) were recruited from a large
      southwestern university in October 2012. METHODS: Utilizing an experimental
      design, participants were assigned to 1 of 3 conditions: an implied motion
      superhero spokes-character, a static superhero spokes-character, and a control
      group. RESULTS: The use of implied motion did not achieve the hypothesized effect
      on message elaboration, but superheroes are a promising persuasive tool for
      health promotion campaigns for college audiences. CONCLUSIONS: Implications for
      sleep health promotion campaigns and the role of implied motion in message design
      strategies are discussed, as well as future directions for research on the
      depiction of implied motion as it relates to theoretical development.

PMID- 25061993
TI  - Depressive symptoms are associated with mental stress-induced myocardial ischemia
      after acute myocardial infarction.
AB  - OBJECTIVES: Depression is an adverse prognostic factor after an acute myocardial
      infarction (MI), and an increased propensity toward emotionally-driven myocardial
      ischemia may play a role. We aimed to examine the association between depressive
      symptoms and mental stress-induced myocardial ischemia in young survivors of an
      MI. METHODS: We studied 98 patients (49 women and 49 men) age 38-60 years who
      were hospitalized for acute MI in the previous 6 months. Patients underwent
      myocardial perfusion imaging at rest, after mental stress (speech task), and
      after exercise or pharmacological stress. A summed difference score (SDS),
      obtained with observer-independent software, was used to quantify myocardial
      ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II)
      was used to measure depressive symptoms, which were analyzed as overall score,
      and as separate somatic and cognitive depressive symptom scores. RESULTS: There
      was a significant positive association between depressive symptoms and SDS with
      mental stress, denoting more ischemia. After adjustment for demographic and
      lifestyle factors, disease severity and medications, each incremental depressive
      symptom was associated with 0.14 points higher SDS. When somatic and cognitive
      depressive symptoms were examined separately, both somatic [beta = 0.17, 95% CI:
      (0.04, 0.30), p = 0.01] and cognitive symptoms [beta = 0.31, 95% CI: (0.07,
      0.56), p = 0.01] were significantly associated with mental stress-induced
      ischemia. Depressive symptoms were not associated with ischemia induced by
      exercise or pharmacological stress. CONCLUSION: Among young post-MI patients,
      higher levels of both cognitive and somatic depressive symptoms are associated
      with a higher propensity to develop myocardial ischemia with mental stress, but
      not with physical (exercise or pharmacological) stress.

PMID- 25061998
TI  - Stress, behavior, and biology: risk factors for cardiovascular diseases in youth.
AB  - Psychological stress reactivity is associated with atherogenesis in youth. The
      novel hypothesis is that stress promotes atherogenic behaviors, including
      snacking on energy-dense food and reducing physical activity, and increases
      adiposity. Stress also increases systolic blood pressure cardiovascular
      reactivity, which also may be atherogenic. Exercise dampens stress reactivity and
      may be one mechanism by which it protects against the development of
      cardiovascular diseases. 

PMID- 25061999
TI  - Revisiting cardiopulmonary exercise testing applications in heart failure:
      aligning evidence with clinical practice.
AB  - American Heart Association/American College of Cardiology class recommendations
      and associated level of evidence for cardiopulmonary exercise testing (CPX) have
      been put forth. A new paradigm is proposed for CPX use and interpretation in
      heart failure (HF). Evidence for this new paradigm will be provided, showing that
      clinical utilization, class recommendations, and the associated level of evidence
      for CPX in the HF population can be expanded significantly. 

PMID- 25062000
TI  - Mitochondrial plasticity with exercise training and extreme environments.
AB  - Mitochondria form a reticulum in skeletal muscle. Exercise training stimulates
      mitochondrial biogenesis, yet an emerging hypothesis is that training also
      induces qualitative regulatory changes. Substrate oxidation, oxygen affinity, and
      biochemical coupling efficiency may be regulated differentially with training and
      exposure to extreme environments. Threshold training doses inducing mitochondrial
      upregulation remain to be elucidated considering fitness level. 

PMID- 25062001
TI  - Influence of sex and estrogen on musculotendinous protein turnover at rest and
      after exercise.
AB  - Women differ from men with regard to muscle and tendon, most likely because of
      sex differences in estrogen. The present experimental findings suggest the
      hypothesis that estrogen has an anabolic effect on muscle primarily by lowering
      the protein turnover and enhancing sensitivity to resistance training.
      Furthermore, estrogen may reduce the stiffness of tendons, an effect that may be
      modified by physical training. 

PMID- 25062002
TI  - Exercise-based fall prevention: can you be a bit more specific?
AB  - Trip-specific perturbation training reduces trip-related falls after laboratory
      induced trips and, prospectively, in the community. Based on an emerging body of
      evidence, we hypothesize that using task-specific perturbation training as a
      stand-alone approach or in conjunction with conventional exercise-based
      approaches will improve the effectiveness of fall prevention interventions
      significantly. 

PMID- 25062003
TI  - Arterial compliance in obese children: implications for cardiovascular health.
AB  - Recent work showed that arterial compliance may be elevated unexpectedly in obese
      children, attributable to accelerated growth and maturation. We hypothesize that
      children with obesity or Type 2 diabetes may reach peak arterial maturation
      earlier in life and then experience an earlier, and potentially more rapid,
      decline in arterial compliance, leading toward earlier cardiovascular disease
      development. 

PMID- 25062004
TI  - Purifying selection in deeply conserved human enhancers is more consistent than
      in coding sequences.
AB  - Comparison of polymorphism at synonymous and non-synonymous sites in protein
      coding DNA can provide evidence for selective constraint. Non-coding DNA that
      forms part of the regulatory landscape presents more of a challenge since there
      is not such a clear-cut distinction between sites under stronger and weaker
      selective constraint. Here, we consider putative regulatory elements termed
      Conserved Non-coding Elements (CNEs) defined by their high level of sequence
      identity across all vertebrates. Some mutations in these regions have been
      implicated in developmental disorders; we analyse CNE polymorphism data to
      investigate whether such deleterious effects are widespread in humans. Single
      nucleotide variants from the HapMap and 1000 Genomes Projects were mapped across
      nearly 2000 CNEs. In the 1000 Genomes data we find a significant excess of rare
      derived alleles in CNEs relative to coding sequences; this pattern is absent in
      HapMap data, apparently obscured by ascertainment bias. The distribution of
      polymorphism within CNEs is not uniform; we could identify two categories of
      sites by exploiting deep vertebrate alignments: stretches that are non-variant,
      and those that have at least one substitution. The conserved category has fewer
      polymorphic sites and a greater excess of rare derived alleles, which can be
      explained by a large proportion of sites under strong purifying selection within
      humans--higher than that for non-synonymous sites in most protein coding regions,
      and comparable to that at the strongly conserved trans-dev genes. Conversely, the
      more evolutionarily labile CNE sites have an allele frequency distribution not
      significantly different from non-synonymous sites. Future studies should exploit
      genome-wide re-sequencing to obtain better coverage in selected non-coding
      regions, given the likelihood that mutations in evolutionarily conserved enhancer
      sequences are deleterious. Discovery pipelines should validate non-coding
      variants to aid in identifying causal and risk-enhancing variants in complex
      disorders, in contrast to the current focus on exome sequencing.

PMID- 25062005
TI  - Click chemistry inspired synthesis and bioevaluation of novel triazolyl
      derivatives of osthol as potent cytotoxic agents.
AB  - A new series of diverse triazoles linked through the hydroxyl group of lactone
      ring opened osthol (1) were synthesized using click chemistry approach. All the
      derivatives were subjected to 3-(4,5-Dimethylthiazol-yl)-diphenyl
      tetrazoliumbromide (MTT) cytotoxicity screening against a panel of seven
      different human cancer cell lines viz. colon (colo-205), colon (HCT-116), breast
      (T47D), lung (NCI-H322), lung (A549), prostate (PC-3) and Skin (A-431) to check
      their cytotoxic potential. Interestingly, among the tested molecules, most of the
      analogs displayed better cytotoxic activity than the parent osthol (1). Of the
      synthesized triazoles, compounds 8 showed the best activity with IC50 of 1.3,
      4.9, 3.6, 41.0, 35.2, 26.4 and 7.2 MUM against colon (Colo-205 and HCT-116),
      breast (T47D), lung (NCI-H322 and A549), prostate (PC-3) and Skin (A-431) cancer
      lines respectively. Compound 8 induced potent apoptotic effects in Colo-205
      cells. The population of apoptotic cells increased from 11.4% in case of negative
      control to 24.1% at 25 MUM of 8. Compound 8 also induced a remarkable decrease in
      mitochondrial membrane potential (LambdaPsim) leading to apoptosis of cancer
      cells used. The present study resulted in identification of broad spectrum
      cytotoxic activity of analogs bearing electron withdrawing substituents, besides
      the enhanced selective activity of analogs with electron donating moieties.

PMID- 25062006
TI  - Synthesis, antitumor activity, and structure-activity relationship study of
      trihydroxylated 2,4,6-triphenyl pyridines as potent and selective topoisomerase
      II inhibitors.
AB  - A series of eighteen trihydroxylated 2,4,6-triphenyl pyridines were designed and
      synthesized which contain hydroxyl groups at ortho, meta or para position of each
      phenyl rings attached to the central pyridine. They were evaluated for
      topoisomerase I and II inhibitory activity, and cytotoxicity against several
      human cancer cell lines for the development of novel anticancer agents. Most of
      the compounds exhibited strong and selective topoisomerase II inhibitory activity
      compared to the positive control, etoposide, and also displayed significant
      cytotoxicity in low micromolar range. Trihydroxylated 2,4,6-triphenyl pyridines
      were more potent than mono- and di-hydroxylated 2,4,6-triphenyl pyridines, which
      have been previously studied in our research group. Positive correlation between
      topoisomerase II inhibitory activity and cytotoxicity was observed for the most
      compounds. Molecular docking study shows qualitatively consistent with the
      results of biological assays. 

PMID- 25062007
TI  - beta-amino-alcohol tethered 4-aminoquinoline-isatin conjugates: synthesis and
      antimalarial evaluation.
AB  - A series of beta-amino alcohol tethered 4-aminoquinoline-isatin conjugates were
      synthesized with the aim of probing their antimalarial structure activity
      relationship. Two of the most active conjugates (11b and 11f) exhibited
      antimalarial efficacy comparable to that of chloroquine, with IC50 values of 11.8
      and 13.5 nM, respectively against chloroquine resistant W2 strain of Plasmodium
      falciparum and are devoid of any cytotoxicity.

PMID- 25062008
TI  - Synthesis and anticonvulsant activity of novel purine derivatives.
AB  - A series of new purines containing triazole and other heterocycle substituents
      was synthesized and evaluated for their preliminary anticonvulsant activity and
      neurotoxicity by using the maximal electroshock (MES), subcutaneous
      pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the
      compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most
      potent compound, with a median effective dose of 23.4 mg/kg and a high protective
      index of more than 25.6 after intraperitoneal administration in mice. Compound 5e
      showed significant oral activity against MES-induced seizures in mice, with an
      ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound
      5e possesses better anticonvulsant activity and is safer than the commercially
      available drugs carbamazepine and valproate in MES, scPTZ and TOX models.

PMID- 25062009
TI  - Synthesis, screening and docking of small heterocycles as glycogen phosphorylase
      inhibitors.
AB  - A series of morpholine substituted amino acids (phenylalanine, leucine, lysine
      and glutamic acid) was synthesized. A fragment-based screening approach was then
      used to evaluate a series of small heterocycles, including morpholine, oxazoline,
      dihydro-1,3-oxazine, tetrahydro-1,3-oxazepine, thiazoline, tetrahydro-1,3
      pyrimidine, tetrahydro-1,3-diazepine and hexahydro-1H-benzimidazole, as potential
      inhibitors of Glycogen Phosphorylase a. Thiazoline 7 displayed an improved
      potency (IC50 of 25 MUM) and had good LE and LELP values, as compared to
      heterocycles 1, 5, 9-13 and 19 (IC50 values of 1.1 mM-23.9 mM). A docking study
      using the crystal structure of human liver Glycogen Phosphorylase, provided
      insight into the interactions of heterocycles 5, 7, 9-13 and 19 with Glycogen
      Phosphorylase.

PMID- 25062010
TI  - Synthesis and antiproliferative activity of 8-hydroxyquinoline derivatives
      containing a 1,2,3-triazole moiety.
AB  - Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by
      performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition ("click" reaction)
      between an 8-O-alkylated-quinoline containing a terminal alkyne and various
      aromatic or protected sugar azides. These compounds were evaluated in vitro for
      their antiproliferative activity on various cancer cell types. Protected sugar
      derivative 16 was the most active compound in the series, exhibiting potent
      antiproliferative activity and high selectivity toward ovarian cancer cells
      (OVCAR-03, GI50 < 0.25 MUg mL(-1)); this derivative was more active than the
      reference drug doxorubicin (OVCAR-03, GI50 = 0.43 MUg mL(-1)). In structure
      activity relationship (SAR) studies, the physico-chemical parameters of the
      compounds were evaluated and docking calculations were performed for the alpha
      glucosidase active site to predict the possible mechanism of action of this
      series of compounds.

PMID- 25062011
TI  - Design, synthesis and antimycobacterial evaluation of 1-(4-(2-substitutedthiazol
      4-yl)phenethyl)-4-(3-(4-substitutedpiperazin-1-yl)alkyl)piperazine hybrid
      analogues.
AB  - A series of twenty six new 1-(4-(2-substitutedthiazol-4-yl)phenethyl)-4-(3-(4
      substitutedpiperazin-1-yl)alkyl)piperazine analogues were synthesized by seven
      steps and evaluated for their anti-tubercular activity against Mycobacterium
      tuberculosis H37Rv strain. Among the tested compounds, 7j, 7p, and 7r exhibited
      moderate activity (MIC = 6.25 MUg/mL) and compounds 7a, 7f, 7g, 7n and 7v
      exhibited good activity (MIC = 3.125 MUg/mL), while 7h displayed excellent
      activity (MIC = 1.56 MUg/mL) by inhibiting 99% growth of M. tuberculosis H37Rv
      strain. In addition, all the active compounds were subjected to cytotoxic studies
      against mouse macrophage (RAW264.7) cell lines and the selectivity index values
      for most of the compounds is >10 indicating suitability of compounds in an
      endeavour to attain lead molecule for further drug development.

PMID- 25062012
TI  - Molecular and morphological identification of mealybug species (Hemiptera:
      Pseudococcidae) in Brazilian vineyards.
AB  - Mealybugs (Hemiptera: Pseudococcidae) are pests constraining the international
      trade of Brazilian table grapes. They damage grapes by transmitting viruses and
      toxins, causing defoliation, chlorosis, and vigor losses and favoring the
      development of sooty mold. Difficulties in mealybug identification remain an
      obstacle to the adequate management of these pests. In this study, our primary
      aim was to identify the principal mealybug species infesting the major table
      grape-producing regions in Brazil, by morphological and molecular
      characterization. Our secondary aim was to develop a rapid identification kit
      based on species-specific Polymerase Chain Reactions, to facilitate the routine
      identification of the most common pest species. We surveyed 40 sites infested
      with mealybugs and identified 17 species: Dysmicoccus brevipes (Cockerell),
      Dysmicoccus sylvarum Williams and Granara de Willink, Dysmicoccus texensis
      (Tinsley), Ferrisia cristinae Kaydan and Gullan, Ferrisia meridionalis Williams,
      Ferrisia terani Williams and Granara de Willink, Phenacoccus baccharidis
      Williams, Phenacoccus parvus Morrison, Phenacoccus solenopsis Tinsley,
      Planococcus citri (Risso), Pseudococcus viburni (Signoret), Pseudococcus cryptus
      Hempel, four taxa closely related each of to Pseudococcus viburni, Pseudococcus
      sociabilis Hambleton, Pseudococcus maritimus (Ehrhorn) and Pseudococcus
      meridionalis Prado, and one specimen from the genus Pseudococcus Westwood. The
      PCR method developed effectively identified five mealybug species of economic
      interest on grape in Brazil: D. brevipes, Pl. citri, Ps. viburni, Ph. solenopsis
      and Planococcus ficus (Signoret). Nevertheless, it is not possible to assure that
      this procedure is reliable for taxa that have not been sampled already and might
      be very closely related to the target species. 

PMID- 25062013
TI  - Granulocyte-colony stimulating factor attenuates oligomeric amyloid beta
      neurotoxicity by activation of neprilysin.
AB  - Soluble oligomeric amyloid beta (oAbeta) causes synaptic dysfunction and neuronal
      cell death, which are involved in the pathogenesis of Alzheimer's disease (AD).
      The hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) is
      expressed in the central nervous system (CNS) and drives neurogenesis. Here we
      show that G-CSF attenuated oAbeta neurotoxicity through the enhancement of the
      enzymatic activity of Abeta-degrading enzyme neprilysin (NEP) in neurons, while
      the NEP inhibitor thiorphan abolished the neuroprotection. Inhibition of
      MEK5/ERK5, a major downstream effector of G-CSF signaling, also ablated
      neuroprotective effect of G-CSF. Furthermore, intracerebroventricular
      administration of G-CSF enhanced NEP enzymatic activity and clearance of Abeta in
      APP/PS1 transgenic mice. Thus, we propose that G-CSF may be a possible
      therapeutic strategy against AD. 

PMID- 25062014
TI  - Mechanical ventilation for comatose patients with inoperative acute intracerebral
      hemorrhage: possible futility of treatment.
AB  - BACKGROUND: Comatose patients with acute intracerebral hemorrhage (ICH) diagnosed
      as inoperative due to their severe comorbidity will be treated differently
      between countries. In certain countries including Japan, aggressive medical care
      may be performed according to the patients' family requests although the effects
      on the outcome are obscure. For respiratory distress in comatose patients with
      inoperative acute ICH, the role of mechanical ventilation on the outcome is
      unknown. We speculated that the efficacy of a ventilator in such a specific
      condition is limited and possibly futile. METHODS: We retrospectively evaluated
      the in-hospital mortality and further outcome of 65 comatose patients with
      inoperative ICH. Among the patients, 56 manifested respiratory distress, and the
      effect of the ventilator was evaluated by comparing the patients treated with and
      without the ventilator. RESULTS: The in-hospital mortality was calculated as 80%.
      A statistically significant parameter affecting the mortality independently was
      the motor subset on the Glasgow Coma Scale (P = 0.015). Among the patients who
      manifested respiratory distress, 7.7% of patients treated with a ventilator and
      14.0% of patients not treated with a ventilator survived; an outcome is not
      significantly different. The mean survival duration of patients treated with a
      ventilator was significantly longer than the mean survival duration of patients
      not treated with a ventilator (P = 0.021). Among the surviving 13 patients, 7
      patients died 5 to 29 months after onset without significant consciousness
      recovery. Another 6 patients suffered continuous disablement due to prolonged
      severe consciousness disturbances. CONCLUSION: The current results indicate that
      treating comatose patients resulting from inoperative acute ICH may be futile. In
      particular, treating these patients with a ventilator only has the effect of
      prolonging unresponsive life, and the treatment may be criticized from the
      perspective of the appropriate use of public medical resources.

PMID- 25062015
TI  - Toxicological assessment of trace beta-diketone antibiotic mixtures on zebrafish
      (Danio rerio) by proteomic analysis.
AB  - beta-Diketone antibiotics (DKAs) can produce chronic toxicity in aquatic
      ecosystems due to their pseudo-persistent in the environment. In this study,
      after long-term DKA exposure to zebrafish (Danio rerio), 47 protein spots had
      greater than 2-fold differential expression as compared to the control; there
      were 26 positive proteins with 14 up-regulated and 12 down-regulated. The main
      functions of the differentially expressed proteins were related to signal
      transduction mechanisms and the cytoskeleton. Of the 26 target genes, 11 genes
      were consistent between their transcriptional and translational levels. Low dose
      DKA exposure (4.69 and 9.38 mg/L) stimulated spontaneous movement in zebrafish.
      Changes in both creatine kinase activity and creatine concentration showed a
      similar trend to zebrafish activity. There was no obvious change in SV-BA after
      DKA exposure, while a reduction of heart rate was concomitant with increasing DKA
      concentrations. DKAs also induced severe histopathological changes in zebrafish
      heart tissue, such as dissolution of cristae and vacuolation of mitochondria.
      These results demonstrated that trace-level DKA exposure affects a variety of
      cellular and biological processes in zebrafish. 

PMID- 25062018
TI  - Botulinum toxin for myofascial pain syndromes in adults.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in Issue 4, 2012. Myofascial pain syndrome (MPS) is a regional muscular pain
      syndrome characterised by the presence of trigger points, which are painful
      points in one or more muscles. The pain can be felt at the site where the trigger
      point is located or it can be felt away from that place when the muscle is
      pressed (referred pain). Botulinum toxin is a protein produced by the bacterium
      Clostridium botulinum and is a potent neurotoxin that eventually inhibits muscle
      contractions. It is capable of selectively weakening painful muscles and
      interrupting the pain cycle. OBJECTIVES: To assess the effectiveness and safety
      of botulinum toxin A (BTXA) in the treatment of myofascial pain syndrome (MPS),
      excluding MPS in neck and head muscles. SEARCH METHODS: This is an updated
      version of the original Cochrane review published in Issue 4, 2012. The search
      strategy for the update was the same as in the original review and we searched
      CENTRAL in The Cochrane Library (2013, Issue 11 of 12), MEDLINE (Ovid) (2012 to
      29 November 2013) and EMBASE (Ovid) (2012 to 27 November 2013). The search
      strategy was composed of terms for myofascial pain and botulinum toxin. For the
      original review, we also searched the Cochrane Pain, Palliative and Supportive
      Care (PaPaS) Review Group Specialised Register until December 2011, PubMed (from
      1966 to 2011) and LILACS (from 1982 to 2011). There was no language restriction.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving
      botulinum toxin for treating participants with MPS. We excluded studies with MPS
      of the neck and head from this review as they have already been assessed in
      existing systematic reviews. We considered a diagnosis of MPS to be based on the
      identification of trigger points in the taut band through palpation of sensitive
      nodules, local twitch response and specific patterns of referred pain associated
      with each trigger point. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened identified studies, extracted data, assessed trial quality
      and analysed results using the Cochrane PaPaS Review Group criteria. MAIN
      RESULTS: Four studies with a total of 233 participants, comparing BTXA with
      placebo, met the inclusion criteria. In one study with 145 participants,
      significant improvement rates of pain intensity scores and duration of daily pain
      were demonstrated when comparing BTXA with placebo. The three other studies
      showed that there was no statistically significant difference between BTXA and
      placebo in pain intensity. AUTHORS' CONCLUSIONS: Since the first publication of
      this review, no new studies were found. There is inconclusive evidence to support
      the use of botulinum toxin in the treatment of MPS based on data from four
      studies with a total of 233 participants, which we considered were of sufficient
      quality to be included in this review. Meta-analyses were not possible due to the
      heterogeneity between studies. We suggest that in future studies the same
      methodology to assess pain, a standardised dose of treatment, follow-up of at
      least four months (to observe the maximum and minimum curve of the drug effect)
      and appropriate data presentation should be used. More high-quality RCTs of
      botulinum toxin for treating MPS need to be conducted before firm conclusions on
      its effectiveness and safety can be drawn.

PMID- 25062017
TI  - Local order in the unfolded state: conformational biases and nearest neighbor
      interactions.
AB  - The discovery of Intrinsically Disordered Proteins, which contain significant
      levels of disorder yet perform complex biologically functions, as well as
      unwanted aggregation, has motivated numerous experimental and theoretical studies
      aimed at describing residue-level conformational ensembles. Multiple lines of
      evidence gathered over the last 15 years strongly suggest that amino acids
      residues display unique and restricted conformational preferences in the unfolded
      state of peptides and proteins, contrary to one of the basic assumptions of the
      canonical random coil model. To fully understand residue level order/disorder,
      however, one has to gain a quantitative, experimentally based picture of
      conformational distributions and to determine the physical basis underlying
      residue-level conformational biases. Here, we review the experimental,
      computational and bioinformatic evidence for conformational preferences of amino
      acid residues in (mostly short) peptides that can be utilized as suitable model
      systems for unfolded states of peptides and proteins. In this context particular
      attention is paid to the alleged high polyproline II preference of alanine. We
      discuss how these conformational propensities may be modulated by peptide solvent
      interactions and so called nearest-neighbor interactions. The relevance of
      conformational propensities for the protein folding problem and the understanding
      of IDPs is briefly discussed. 

PMID- 25062019
TI  - The games plant viruses play.
AB  - Mixed virus infections in plants are common in nature. The outcome of such virus
      virus interactions ranges from cooperation and coexistence (synergism) to mutual
      exclusion (antagonism). A priori, the outcome of mixed infections is hard to
      predict. To date, the analyses of plant virus mixed infections were limited to
      reports of emerging symptoms and/or to qualitative, at best quantitative,
      descriptions of the accumulation of both viruses. Here, we show that evolutionary
      game theory provides an adequate theoretical framework to analyze mixed viral
      infections and to predict the long-term evolution of the mixed populations. 

PMID- 25062020
TI  - Antibacterial activities of plant-derived compounds and essential oils toward
      Cronobacter sakazakii and Cronobacter malonaticus.
AB  - Cronobacter sakazakii and C. malonaticus are opportunistic pathogens that cause
      infections in children and immunocompromised adults. In the present study, the
      antibacterial activity of 19 plant-derived compounds, 5 essential oils, and an
      extract of propolis were assessed against C. sakazakii and C. malonaticus. The
      effects of most of these antimicrobials have not been reported previously. Both
      strains were susceptible to thymol, carvacrol, thymoquinone, p-cymene, linalool,
      camphor, citral, eugenol, and trans-cinnamaldehyde as well as cinnamon,
      lemongrass, oregano, clove, and laurel essential oils; their minimum inhibitory
      concentrations varied between 0.1 and 2.0 mg/mL. As an alternative treatment
      method, vapors of the volatiles were tested as an indirect treatment. Vapors of
      trans-cinnamaldehyde, eugenol, oregano, and cinnamon essential oils inhibited
      both tested strains, while vapors of linalool were only active against C.
      sakazakii. To our knowledge, this study is the first time that the inhibitory
      activity of the vapors of these compounds and essential oils has been reported
      against Cronobacter spp.

PMID- 25062021
TI  - Origin and consequences of the relationship between protein mean and variance.
AB  - Cell-to-cell variance in protein levels (noise) is a ubiquitous phenomenon that
      can increase fitness by generating phenotypic differences within clonal
      populations of cells. An important challenge is to identify the specific
      molecular events that control noise. This task is complicated by the strong
      dependence of a protein's cell-to-cell variance on its mean expression level
      through a power-law like relationship (sigma2?MU1.69). Here, we dissect the
      nature of this relationship using a stochastic model parameterized with
      experimentally measured values. This framework naturally recapitulates the power
      law like relationship (sigma2?MU1.6) and accurately predicts protein variance
      across the yeast proteome (r2 = 0.935). Using this model we identified two
      distinct mechanisms by which protein variance can be increased. Variables that
      affect promoter activation, such as nucleosome positioning, increase protein
      variance by changing the exponent of the power-law relationship. In contrast,
      variables that affect processes downstream of promoter activation, such as mRNA
      and protein synthesis, increase protein variance in a mean-dependent manner
      following the power-law. We verified our findings experimentally using an
      inducible gene expression system in yeast. We conclude that the power-law-like
      relationship between noise and protein mean is due to the kinetics of promoter
      activation. Our results provide a framework for understanding how molecular
      processes shape stochastic variation across the genome. 

PMID- 25062022
TI  - Characterization of the small exported Plasmodium falciparum membrane protein
      SEMP1.
AB  - Survival and virulence of the human malaria parasite Plasmodium falciparum during
      the blood stage of infection critically depend on extensive host cell
      refurbishments mediated through export of numerous parasite proteins into the
      host cell. The parasite-derived membranous structures called Maurer's clefts (MC)
      play an important role in protein trafficking from the parasite to the red blood
      cell membrane. However, their specific function has yet to be determined. We
      identified and characterized a new MC membrane protein, termed small exported
      membrane protein 1 (SEMP1). Upon invasion it is exported into the RBC cytosol
      where it inserts into the MCs before it is partly translocated to the RBC
      membrane. Using conventional and conditional loss-of-function approaches we
      showed that SEMP1 is not essential for parasite survival, gametocytogenesis, or
      PfEMP1 export under culture conditions. Co-IP experiments identified several
      potential interaction partners, including REX1 and other membrane-associated
      proteins that were confirmed to co-localize with SEMP1 at MCs. Transcriptome
      analysis further showed that expression of a number of exported parasite proteins
      was up-regulated in SEMP1-depleted parasites. By using Co-IP and transcriptome
      analysis for functional characterization of an exported parasite protein we
      provide a new starting point for further detailed dissection and characterisation
      of MC-associated protein complexes. 

PMID- 25062024
TI  - N-phenacylthiazolium bromide reduces bone fragility induced by nonenzymatic
      glycation.
AB  - Nonenzymatic glycation (NEG) describes a series of post-translational
      modifications in the collagenous matrices of human tissues. These modifications,
      known as advanced glycation end-products (AGEs), result in an altered collagen
      crosslink profile which impacts the mechanical behavior of their constituent
      tissues. Bone, which has an organic phase consisting primarily of type I
      collagen, is significantly affected by NEG. Through constant remodeling by
      chemical resorption, deposition and mineralization, healthy bone naturally
      eliminates these impurities. Because bone remodeling slows with age, AGEs
      accumulate at a greater rate. An inverse correlation between AGE content and
      material-level properties, particularly in the post-yield region of deformation,
      has been observed and verified. Interested in reversing the negative effects of
      NEG, here we evaluate the ability of n-phenacylthiazolium bromide (PTB) to cleave
      AGE crosslinks in human cancellous bone. Cancellous bone cylinders were obtained
      from nine male donors, ages nineteen to eighty, and subjected to one of six PTB
      treatments. Following treatment, each specimen was mechanically tested under
      physiological conditions to failure and AGEs were quantified by fluorescence.
      Treatment with PTB showed a significant decrease in AGE content versus control
      NEG groups as well as a significant rebound in the post-yield material level
      properties (p<0.05). The data suggest that treatment with PTB could be an
      effective means to reduce AGE content and decrease bone fragility caused by NEG
      in human bone. 

PMID- 25062025
TI  - Impact of dietary selenium on methylmercury toxicity in juvenile Atlantic cod: a
      transcriptional survey.
AB  - Selenium (Se) and its derivatives are known to have protective effects against
      mercury (Hg) toxicity in mammals. In this study we wanted to evaluate whether Se
      co-exposure affect the transcription of methylmercury (MeHg) toxicity-relevant
      genes in early life stages of fish. Juvenile Atlantic cod were exposed to regular
      feed (control), Se-spiked feed (3mg Se kg(-1)), MeHg-spiked feed (10mg Hg kg(-1))
      or to Se- and MeHg-spiked feed (3mg Se kg(-1) and 10mg Hg kg(-1), respectively)
      for ten weeks. Liver tissue was harvested for transcriptional analysis when the
      fish were weighing 11.4 +/- 3.2g. Accumulated levels of Hg in liver of the two
      groups of fish exposed to MeHg were 1.5mg Hg kg(-1) wet weight, or 44-fold higher
      than in the control group, while the Se concentrations differed with less than 2
      fold between the fish groups. Selenium co-exposure had no effect on the
      accumulated levels of Hg in liver tissue; however, MeHg co-exposure reduced the
      accumulated level of Se. Dietary exposure to MeHg had no effect on fish growth.
      Interaction effects between Se and MeHg exposure were observed for the
      transcriptional levels of CAT, GPX1, GPX3, NFE2L2, UBA52, SEPP1 and DNMT1.
      Significant effects of MeHg exposure were seen for DNMT1 and PPARG, while effects
      of Se exposure were seen for GPX4B and SEPP1A, as well as for DNA
      methyltransferase activity. The transcriptional results suggest, by considering
      up-regulation as a proxy for negative impact and at the tested concentrations, a
      pro-oxidative effect of Se co-exposure with MeHg, rather than an antioxidative
      effect.

PMID- 25062026
TI  - Photo-induced toxicity of titanium dioxide nanoparticles to Daphnia magna under
      natural sunlight.
AB  - Titanium dioxide nanoparticles (TiO2 NP) are one of the most abundantly utilized
      nanoparticles in the world. Studies have demonstrated the ability of the anatase
      crystal of TiO2 NP to produce reactive oxygen species (ROS) in the presence of
      ultraviolet radiation (UVR), a co-exposure likely to occur in aquatic ecosystems.
      The goal of this study was to examine the photo-induced toxicity of anatase TiO2
      NP under natural sunlight to Daphnia magna. D. magna were exposed to a range of
      UVR intensities and anatase TiO2 concentrations in an outdoor exposure system
      using the sun as the source of UVR. Different UVR intensities were achieved using
      UVR opaque and transparent plastics. AnataseTiO2-NP demonstrated the reciprocal
      relationship seen in other phototoxic compounds such as polycyclic aromatic
      hydrocarbons (PAHs) at higher UVR treatments. The calculated 8h LC50 of anatase
      TiO2 NP was 139 ppb under full intensity ambient natural sunlight, 778 ppb under
      50% natural sunlight, and >500 ppm under 10% natural sunlight. Mortality was also
      compared between animals allowed to accumulate a body burden of anatase TiO2 for
      1h and organisms whose first exposure to anatase TiO2 aqueous suspensions
      occurred under UVR. A significantly greater toxic effect was observed in aqueous,
      low body burden suspensions than that of TiO2 1h body burdens, which is
      dissimilar from the model presented in PAHs. Anatase TiO2 presents a unique photo
      induced toxic model that is different than that of established phototoxic
      compounds.

PMID- 25062028
TI  - Preliminary outcomes of a pilot physical therapy program for HIV-infected
      patients with chronic pain.
AB  - Chronic pain in HIV-infected individuals is common and often undertreated.
      Physical therapy (PT) is an evidence-based nonpharmacologic treatment for chronic
      pain. Our objective is to present the results of a pilot PT program in an HIV
      pain/palliative care clinic, which is embedded within a Ryan White-funded
      multidisciplinary HIV primary care clinic. Medical records of HIV-infected
      patients participating in a PT program between November 2012 and July 2013 were
      retrospectively reviewed. Pain scores on a 0-10 scale and cost data were
      collected and analyzed. Among 43 patients referred, 27 collectively attended 86
      sessions. Median age of enrolled patients was 54 (IQR 49-58). Sixteen (59%) were
      African-American and 20 (77%) had an undetectable HIV viral load. Mean pain score
      at initial visit was 6.5 (SD = 1.1). The average session-level decrease was 2.6
      (SD = 1.7) and patient-level decrease was 2.5 (SD = 1.2). The largest payors were
      Medicare managed care (28%), Medicaid (21%), and Ryan White grant-related funds
      (18%). When the first four months of the program are excluded to account for slow
      start-up, the program's monthly net revenue during the remaining five months was
      $163. We present preliminary data from a low-cost pilot PT program integrated
      into an HIV clinic in a primary care setting associated with clinically
      significant improvements in pain. Further investigation into the implementation
      of such programs is essential. 

PMID- 25062029
TI  - Optical imaging of neuronal activity and visualization of fine neural structures
      in non-desheathed nervous systems.
AB  - Locating circuit neurons and recording from them with single-cell resolution is a
      prerequisite for studying neural circuits. Determining neuron location can be
      challenging even in small nervous systems because neurons are densely packed,
      found in different layers, and are often covered by ganglion and nerve sheaths
      that impede access for recording electrodes and neuronal markers. We revisited
      the voltage-sensitive dye RH795 for its ability to stain and record neurons
      through the ganglion sheath. Bath-application of RH795 stained neuronal membranes
      in cricket, earthworm and crab ganglia without removing the ganglion sheath,
      revealing neuron cell body locations in different ganglion layers. Using the
      pyloric and gastric mill central pattern generating neurons in the stomatogastric
      ganglion (STG) of the crab, Cancer borealis, we found that RH795 permeated the
      ganglion without major residue in the sheath and brightly stained somatic, axonal
      and dendritic membranes. Visibility improved significantly in comparison to
      unstained ganglia, allowing the identification of somata location and number of
      most STG neurons. RH795 also stained axons and varicosities in non-desheathed
      nerves, and it revealed the location of sensory cell bodies in peripheral nerves.
      Importantly, the spike activity of the sensory neuron AGR, which influences the
      STG motor patterns, remained unaffected by RH795, while desheathing caused
      significant changes in AGR activity. With respect to recording neural activity,
      RH795 allowed us to optically record membrane potential changes of sub-sheath
      neuronal membranes without impairing sensory activity. The signal-to-noise ratio
      was comparable with that previously observed in desheathed preparations and
      sufficiently high to identify neurons in single-sweep recordings and synaptic
      events after spike-triggered averaging. In conclusion, RH795 enabled staining and
      optical recording of neurons through the ganglion sheath and is therefore both a
      good anatomical marker for living neural tissue and a promising tool for studying
      neural activity of an entire network with single-cell resolution. 

PMID- 25062030
TI  - Microcontact peeling as a new method for cell micropatterning.
AB  - Micropatterning is becoming a powerful tool for studying morphogenetic and
      differentiation processes of cells. Here we describe a new micropatterning
      technique, which we refer to as microcontact peeling. Polydimethylsiloxane (PDMS)
      substrates were treated with oxygen plasma, and the resulting hydrophilic layer
      of the surface was locally peeled off through direct contact with a peeling stamp
      made of aluminum, copper, or silicon. A hydrophobic layer of PDMS could be
      selectively exposed only at the places of the physical contact as revealed by
      water contact angle measurements and angle-resolved X-ray photoelectron
      spectroscopy, which thus enabled successful micropatterning of cells with micro
      featured peeling stamps. This new micropatterning technique needs no procedure
      for directly adsorbing proteins to bare PDMS in contrast to conventional
      techniques using a microcontact printing stamp. Given the several unique
      characteristics, the present technique based on the peel-off of inorganic
      materials may become a useful option for performing cell micropatterning. 

PMID- 25062031
TI  - Systematic approach to in-depth understanding of photoelectrocatalytic bacterial
      inactivation mechanisms by tracking the decomposed building blocks.
AB  - A systematic approach was developed to understand, in-depth, the mechanisms
      involved during the inactivation of bacterial cells using photoelectrocatalytic
      (PEC) processes with Escherichia coli K-12 as the model microorganism. The
      bacterial cells were found to be inactivated and decomposed primarily due to
      attack from photogenerated H2O2. Extracellular reactive oxygen species (ROSs),
      such as H2O2, may penetrate into the bacterial cell and cause dramatically
      elevated intracellular ROSs levels, which would overwhelm the antioxidative
      capacity of bacterial protective enzymes such as superoxide dismutase and
      catalase. The activities of these two enzymes were found to decrease due to the
      ROSs attacks during PEC inactivation. Bacterial cell wall damage was then
      observed, including loss of cell membrane integrity and increased permeability,
      followed by the decomposition of cell envelope (demonstrated by scanning
      electronic microscope images). One of the bacterial building blocks, protein, was
      found to be oxidatively damaged due to the ROSs attacks, as well. Leakage of
      cytoplasm and biomolecules (bacterial building blocks such as proteins and
      nucleic acids) were evident during prolonged PEC inactivation process. The leaked
      cytoplasmic substances and cell debris could be further degraded and, ultimately,
      mineralized with prolonged PEC treatment. 

PMID- 25062032
TI  - Localization and mobility of synaptic vesicles in Myosin VI mutants of
      Drosophila.
AB  - BACKGROUND: At the Drosophila neuromuscular junction (NMJ), synaptic vesicles are
      mobile; however, the mechanisms that regulate vesicle traffic at the nerve
      terminal are not fully understood. Myosin VI has been shown to be important for
      proper synaptic physiology and morphology at the NMJ, likely by functioning as a
      vesicle tether. Here we investigate vesicle dynamics in Myosin VI mutants of
      Drosophila. RESULTS: In Drosophila, Myosin VI is encoded by the gene, jaguar
      (jar). To visualize active vesicle cycling we used FM dye loading and compared
      loss of function alleles of jar with controls. These studies revealed a
      differential distribution of vesicles at the jar mutant nerve terminal, with the
      newly endocytosed vesicles observed throughout the mutant boutons in contrast to
      the peripheral localization visualized at control NMJs. This finding is
      consistent with a role for Myosin VI in restraining vesicle mobility at the
      synapse to ensure proper localization. To further investigate regulation of
      vesicle dynamics by Myosin VI, FRAP analysis was used to analyze movement of GFP
      labeled synaptic vesicles within individual boutons. FRAP revealed that synaptic
      vesicles are moving more freely in the jar mutant boutons, indicated by changes
      in initial bleach depth and rapid recovery of fluorescence following
      photobleaching. CONCLUSION: This data provides insights into the role for Myosin
      VI in mediating synaptic vesicle dynamics at the nerve terminal. We observed
      mislocalization of actively cycling vesicles and an apparent increase in vesicle
      mobility when Myosin VI levels are reduced. These observations support the notion
      that a major function of Myosin VI in the nerve terminal is tethering synaptic
      vesicles to proper sub-cellular location within the bouton.

PMID- 25062033
TI  - Native rodent species are unlikely sources of infection for Leishmania (Viannia)
      braziliensis along the Transoceanic Highway in Madre de Dios, Peru.
AB  - An estimated 2.3 million disability-adjusted life years are lost globally from
      leishmaniasis. In Peru's Amazon region, the department of Madre de Dios (MDD)
      rises above the rest of the country in terms of the annual incidence rates of
      human leishmaniasis. Leishmania (Viannia) braziliensis is the species most
      frequently responsible for the form of disease that results in tissue destruction
      of the nose and mouth. However, essentially nothing is known regarding the
      reservoirs of this vector-borne, zoonotic parasite in MDD. Wild rodents have been
      suspected, or proven, to be reservoirs of several Leishmania spp. in various
      ecosystems and countries. Additionally, people who live or work in forested
      terrain, especially those who are not regionally local and whose immune systems
      are thus naive to the parasite, are at most risk for contracting L. (V.)
      braziliensis. Hence, the objective of this study was to collect tissues from wild
      rodents captured at several study sites along the Amazonian segment of the newly
      constructed Transoceanic Highway and to use molecular laboratory techniques to
      analyze samples for the presence of Leishmania parasites. Liver tissues were
      tested via polymerase chain reaction from a total of 217 rodents; bone marrow and
      skin biopsies (ear and tail) were also tested from a subset of these same
      animals. The most numerous rodent species captured and tested were Oligoryzomys
      microtis (40.7%), Hylaeamys perenensis (15.7%), and Proechimys spp. (12%). All
      samples were negative for Leishmania, implying that although incidental
      infections may occur, these abundant rodent species are unlikely to serve as
      primary reservoirs of L. (V.) braziliensis along the Transoceanic Highway in MDD.
      Therefore, although these rodent species may persist and even thrive in
      moderately altered landscapes, we did not find any evidence to suggest they pose
      a risk for L. (V.) braziliensis transmission to human inhabitants in this highly
      prevalent region. 

PMID- 25062034
TI  - delta18O in the tropical conifer Agathis robusta records ENSO-related
      precipitation variations.
AB  - Long-lived trees from tropical Australasia are a potential source of information
      about internal variability of the El Nino-Southern Oscillation (ENSO), because
      they occur in a region where precipitation variability is closely associated with
      ENSO activity. We measured tree-ring width and oxygen isotopic composition
      (delta18O) of alpha-cellulose from Agathis robusta (Queensland Kauri) samples
      collected in the Atherton Tablelands, Queensland, Australia. Standard ring-width
      chronologies yielded low internal consistency due to the frequent presence of
      false ring-like anatomical features. However, in a detailed examination of the
      most recent 15 years of growth (1995-2010), we found significant correlation
      between delta18O and local precipitation, the latter associated with ENSO
      activity. The results are consistent with process-based forward modeling of the
      oxygen isotopic composition of alpha-cellulose. The delta18O record also enabled
      us to confirm the presence of a false growth ring in one of the three samples in
      the composite record, and to determine that it occurred as a consequence of
      anomalously low rainfall in the middle of the 2004/5 rainy season. The
      combination of incremental growth and isotopic measures may be a powerful
      approach to development of long-term (150+ year) ENSO reconstructions from the
      terrestrial tropics of Australasia.

PMID- 25062035
TI  - Rapid whole-genome sequencing for surveillance of Salmonella enterica serovar
      enteritidis.
AB  - For Salmonella enterica serovar Enteritidis, 85% of isolates can be classified
      into 5 pulsed-field gel electrophoresis (PFGE) types. However, PFGE has limited
      discriminatory power for outbreak detection. Although whole-genome sequencing has
      been found to improve discrimination of outbreak clusters, whether this procedure
      can be used in real-time in a public health laboratory is not known. Therefore,
      we conducted a retrospective and prospective analysis. The retrospective study
      investigated isolates from 1 confirmed outbreak. Additional cases could be
      attributed to the outbreak strain on the basis of whole-genome data. The
      prospective study included 58 isolates obtained in 2012, including isolates from
      1 epidemiologically defined outbreak. Whole-genome sequencing identified
      additional isolates that could be attributed to the outbreak, but which differed
      from the outbreak-associated PFGE type. Additional putative outbreak clusters
      were detected in the retrospective and prospective analyses. This study
      demonstrates the practicality of implementing this approach for outbreak
      surveillance in a state public health laboratory. 

PMID- 25062037
TI  - Voltage charging enhances ionic conductivity in gold nanotube membranes.
AB  - Ionically conductive membranes are used in many electrochemical processes and
      devices, including batteries, fuel cells, and electrolyzers. In all such
      applications, it is advantageous to use membranes with high ionic conductivity
      because membrane resistance causes a voltage loss suffered by the cell. We
      describe here a method for enhancing ionic conductivity in membranes containing
      small diameter (4 nm) gold nanotubes. This entails making the gold nanotube
      membrane the working electrode in an electrochemical cell and applying a voltage
      to the membrane. We show here that voltage charging in this way can increase
      membrane ionic conductivity by over an order of magnitude. When expressed in
      terms of the ionic conductivity of the electrolyte, kappa, within an individual
      voltage-charged tube, the most negative applied voltage yielded a kappa
      comparable to that of 1 M aqueous KCl, over 2 orders of magnitude higher than
      kappa of the 0.01 M KCl solution contacting the membrane. 

PMID- 25062036
TI  - Chemical reporter for visualizing metabolic cross-talk between carbohydrate
      metabolism and protein modification.
AB  - Metabolic chemical reporters have been largely used to study posttranslational
      modifications. Generally, it was assumed that these reporters entered one
      biosynthetic pathway, resulting in labeling of one type of modification. However,
      because they are metabolized by cells before their addition onto proteins,
      metabolic chemical reporters potentially provide a unique opportunity to read-out
      on both modifications of interest and cellular metabolism. We report here the
      development of a metabolic chemical reporter 1-deoxy-N-pentynyl glucosamine (1
      deoxy-GlcNAlk). This small-molecule cannot be incorporated into glycans; however,
      treatment of mammalian cells results in labeling of a variety proteins and
      enables their visualization and identification. Competition of this labeling with
      sodium acetate and an acetyltransferase inhibitor suggests that 1-deoxy-GlcNAlk
      can enter the protein acetylation pathway. These results demonstrate that
      metabolic chemical reporters have the potential to isolate and potentially
      discover cross-talk between metabolic pathways in living cells. 

PMID- 25062039
TI  - Analytical model of an isolated single-atom electron source.
AB  - An analytical model of a single-atom electron source is presented, where
      electrons are created by near-threshold photoionization of an isolated atom. The
      model considers the classical dynamics of the electron just after the photon
      absorption, i.e. its motion in the potential of a singly charged ion and a
      uniform electric field used for acceleration. From closed expressions for the
      asymptotic transverse electron velocities and trajectories, the effective source
      temperature and the virtual source size can be calculated. The influence of the
      acceleration field strength and the ionization laser energy on these properties
      has been studied. With this model, a single-atom electron source with the optimum
      electron beam properties can be designed. Furthermore, we show that the model is
      also applicable to ionization of rubidium atoms, and thus also describes the
      ultracold electron source, which is based on photoionization of laser-cooled
      alkali atoms. 

PMID- 25062038
TI  - Serum autotaxin is a parameter for the severity of liver cirrhosis and overall
      survival in patients with liver cirrhosis--a prospective cohort study.
AB  - BACKGROUND: Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are
      considered to be involved in the development of liver fibrosis and elevated
      levels of serum ATX have been found in patients with hepatitis C virus associated
      liver fibrosis. However, the clinical role of systemic ATX in the stages of liver
      cirrhosis was unknown. Here we investigated the relation of ATX serum levels and
      severity of cirrhosis as well as prognosis of cirrhotic patients. METHODS:
      Patients with liver cirrhosis were prospectively enrolled and followed until
      death, liver transplantation or last contact. Blood samples drawn at the day of
      inclusion in the study were assessed for ATX content by an enzyme-linked
      immunosorbent assay. ATX levels were correlated with the stage as well as
      complications of cirrhosis. The prognostic value of ATX was investigated by uni-
      and multivariate Cox regression analyses. LPA concentration was determined by
      liquid chromatography-tandem mass spectrometry. RESULTS: 270 patients were
      enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as
      compared to healthy subjects (0.814+/-0.42 mg/l vs. 0.258+/-0.40 mg/l, P<0.001).
      Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end
      stage liver disease) score and LPA levels (r = 0.493, P = 0.027). Patients with
      hepatic encephalopathy (P = 0.006), esophageal varices (P = 0.002) and portal
      hypertensive gastropathy (P = 0.008) had higher ATX levels than patients without
      these complications. Low ATX levels were a parameter independently associated
      with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365
      0.905, P = 0.017). CONCLUSION: Serum ATX is an indicator for the severity of
      liver disease and the prognosis of cirrhotic patients.

PMID- 25062040
TI  - Dynamical effects in strain measurements by dark-field electron holography.
AB  - Here, we study the effect of dynamic scattering on the projected geometric phase
      and strain maps reconstructed using dark-field electron holography (DFEH) for non
      uniformly strained crystals. The investigated structure consists of a {SiGe/Si}
      superlattice grown on a (001)-Si substrate. The three-dimensional strain field
      within the thin TEM lamella is modelled by the finite element method. The
      observed projected strain is simulated in two ways by multiplying the strain at
      each depth in the crystal by a weighting function determined from a recently
      developed analytical two-beam dynamical theory, and by simply taking the average
      value. We demonstrate that the experimental results need to be understood in
      terms of the dynamical theory and good agreement is found between the
      experimental and simulated results. Discrepancies do remain for certain cases and
      are likely to be from an imprecision in the actual two-beam diffraction
      conditions, notably the deviation parameter, and points to limitations in the 2
      beam approximation. Finally, a route towards a 3D reconstruction of strain fields
      is proposed. 

PMID- 25062041
TI  - Atmospheric scanning electron microscope system with an open sample chamber:
      configuration and applications.
AB  - An atmospheric scanning electron microscope (ASEM) with an open sample chamber
      and optical microscope (OM) is described and recent developments are reported. In
      this ClairScope system, the base of the open sample dish is sealed to the top of
      the inverted SEM column, allowing the liquid-immersed sample to be observed by OM
      from above and by SEM from below. The optical axes of the two microscopes are
      aligned, ensuring that the same sample areas are imaged to realize quasi
      simultaneous correlative microscopy in solution. For example, the
      cathodoluminescence of ZnO particles was directly demonstrated. The improved
      system has (i) a fully motorized sample stage, (ii) a column protection system in
      the case of accidental window breakage, and (iii) an OM/SEM operation system
      controlled by a graphical user interface. The open sample chamber allows the
      external administration of reagents during sample observation. We monitored the
      influence of added NaCl on the random motion of silica particles in liquid.
      Further, using fluorescence as a transfection marker, the effect of small
      interfering RNA-mediated knockdown of endogenous Varp on Tyrp1 trafficking in
      melanocytes was examined. A temperature-regulated titanium ASEM dish allowed the
      dynamic observation of colloidal silver nanoparticles as they were heated to 240
      degrees C and sintered. 

PMID- 25062042
TI  - Regulation of cardiac expression of the diabetic marker microRNA miR-29.
AB  - Diabetes mellitus (DM) is an independent risk factor for heart disease and its
      underlying mechanisms are unclear. Increased expression of diabetic marker miR-29
      family miRNAs (miR-29a, b and c) that suppress the pro-survival protein Myeloid
      Cell Leukemia 1(MCL-1) is reported in pancreatic beta-cells in Type 1 DM. Whether
      an up-regulation of miR-29 family miRNAs and suppression of MCL-1 (dysregulation
      of miR-29-MCL-1 axis) occurs in diabetic heart is not known. This study tested
      the hypothesis that insulin regulates cardiac miR-29-MCL-1 axis and its
      dysregulation correlates with DM progression. In vitro studies with mouse
      cardiomyocyte HL-1 cells showed that insulin suppressed the expression of miR
      29a, b and c and increased MCL-1 mRNA. Conversely, Rapamycin (Rap), a drug
      implicated in the new onset DM, increased the expression of miR-29a, b and c and
      suppressed MCL-1 and this effect was reversed by transfection with miR-29
      inhibitors. Rap inhibited mammalian target of rapamycin complex 1 (mTORC1)
      signaling in HL-1 cells. Moreover, inhibition of either mTORC1 substrate S6K1 by
      PF-4708671, or eIF4E-induced translation by 4E1RCat suppressed MCL-1. We used
      Zucker diabetic fatty (ZDF) rat, a rodent model for DM, to test whether
      dysregulation of cardiac miR-29-MCL-1 axis correlates with DM progression. 11
      week old ZDF rats exhibited significantly increased body weight, plasma glucose,
      insulin, cholesterol, triglycerides, body fat, heart weight, and decreased lean
      muscle mass compared to age-matched lean rats. Rap treatment (1.2 mg/kg/day, from
      9-weeks to 15-weeks) significantly reduced plasma insulin, body weight and heart
      weight, and severely dysregulated cardiac miR-29-MCL1 axis in ZDF rats.
      Importantly, dysregulation of cardiac miR-29-MCL-1 axis in ZDF rat heart
      correlated with cardiac structural damage (disorganization or loss of myofibril
      bundles). We conclude that insulin and mTORC1 regulate cardiac miR-29-MCL-1 axis
      and its dysregulation caused by reduced insulin and mTORC1 inhibition increases
      the vulnerability of a diabetic heart to structural damage. 

PMID- 25062043
TI  - Human infection with West Nile Virus, Xinjiang, China, 2011.

PMID- 25062045
TI  - Dynamic recruitment of protein tyrosine phosphatase PTPD1 to EGF stimulation
      sites potentiates EGFR activation.
AB  - Balanced activity of protein tyrosine kinases and phosphatases (PTPs) controls
      tyrosine phosphorylation levels and, consequently, is needed to prevent
      pathologies like cancer. Phosphatase activity is tightly regulated in space and
      time. Thus, in order to understand how phospho-tyrosine signalling is regulated,
      the intracellular dynamics of PTPs should be investigated. Here, we have studied
      the intracellular dynamics of PTPD1, a FERM (four-point-one, ezrin, radixin,
      moesin) domain-containing PTP that is over expressed in cancer cells and
      potentiates EGFR signalling. Whereas PTPD1 was excluded from E-cadherin rich cell
      cell adhesions in epithelial cell monolayers, it diffused from the cytoplasm to
      those membranes in contact with the extracellular medium. Localisation of PTPD1
      at the plasma membrane was mediated by its FERM domain and enabled the formation
      of EGFR/PTPD1-containing signalling complexes that pre-existed at the plasma
      membrane before EGF stimulation. PTPD1 and EGFR transiently co-localised at EGF
      stimulation sites until the formation of macropinosomes containing active species
      of EGFR. Interference of PTPD1 expression caused a decrease in EGFR
      phosphorylated species at the periphery of the cell. Presented data suggest that
      the transient formation of dynamic PTPD1/EGFR signalling complexes strengthens
      EGF signalling by promoting the spatial propagation of EGFR phosphorylated
      species. 

PMID- 25062048
TI  - Synthesis, crystal growth, characterization and theoretical studies of 4
      aminobenzophenonium picrate.
AB  - Single crystals of 4-aminobenzophenonium picrate (4ABPP) were grown by slow
      evaporation of a mixed solvent system methanol-acetone (1:1,v/v) containing
      equimolar quantities of picric acid and 4-aminobenzophenone. The proton and
      carbon signals are confirmed by nuclear magnetic resonance spectroscopy. The
      various functional groups present in the molecule are identified by FT-IR
      analysis. Optimized geometry, first-order molecular hyperpolarizability (beta),
      polarizability (alpha), bond length, bond angles and excited state energy from
      theoretical UV were derived by Hartree-Fock calculations. The complete assignment
      of the vibrational modes for 4-aminobenzophenonium picrate was performed by the
      scaled quantum mechanics force field (SQMFF) methodology using potential energy
      distribution. Natural bond orbital (NBO) calculations were employed to study the
      stabilities arising from charge delocalization and intermolecular interactions of
      4ABPP. The atomic charge distributions of the various atoms present in 4ABPP are
      obtained by Mulliken charge population analysis. The as-grown crystal is further
      characterized by thermal and optical absorbance studies. 

PMID- 25062049
TI  - The influence of the various central metals on photophysical and photochemical
      properties of benzothiazole-substituted phthalocyanines.
AB  - The photophysical (fluorescence quantum yields and lifetimes, fluorescence
      quenching studies by 1,4-benzoquinone (BQ)) and photochemical (singlet oxygen
      quantum yields and photodegradation studies under light irradiation) properties
      of tetra-benzothiazole substituted metal-free (H2Pc, 1), lead (II) (PbPc, 2) and
      zinc(II) (ZnPc, 3) phthalocyanine compounds were investigated in tetrahydrofuran
      (THF) solution. All of these compounds did not show any aggregation and they
      produced good singlet oxygen (especially ZnPc). The influence of the various
      central metal ions (zinc, lead or without metal) on the photophysical and
      photochemical parameters was also investigated and compared. 

PMID- 25062050
TI  - Asymmetric multibranched conjugated molecules: synthesis, structure and
      photophysical properties.
AB  - The symmetric multibranched pi-conjugated compounds with C3 or C6 configuration
      have been intensively studied. The reports on asymmetric multibranched compounds
      are very limited. In this work, we designed and synthesized two asymmetric
      multibranched pi-conjugated molecules using truxene as the central core,
      diphenylamino and thiophenyl (or thiophenylethynyl) groups as the different
      branches respectively: 2,7-di(N,N-diphenylamino)-12-(2-thiophenyl)
      5,5',10,10',15,15'-hexaethyltruxene and 2,7-di(N,N-diphenylamino)-12-(2
      thiophenylethynyl)-5,5',10,10',15,15'-hexaethyltruxene. Their photophysical
      properties have been explored combining with their theoretical calculation and X
      ray single-crystal structure of a key intermediate. Though their different pi
      conjugation length of branches, the two title compounds exhibit almost same
      absorption maxima. However, their emission peaks behave a gradual red-shift with
      the increase of the conjugation length. The theoretical calculation results
      indicate that the two asymmetric compounds behave a main transition from the HOMO
      1 to the LUMO or from the HOMO to the LUMO+1 upon excited. 

PMID- 25062051
TI  - Microwave-assisted of dispersive liquid-liquid microextraction and
      spectrophotometric determination of uranium after optimization based on Box
      Behnken design and chemometrics methods.
AB  - In this study an analytical procedure based on microwave-assisted dispersive
      liquid-liquid microextraction (MA-DLLME) and spectrophotometric coupled with
      chemometrics methods is proposed to determine uranium. In the proposed method, 4
      (2-pyridylazo) resorcinol (PAR) is used as a chelating agent, and chloroform and
      ethanol are selected as extraction and dispersive solvent. The optimization
      strategy is carried out by using two level full factorial designs. Results of the
      two level full factorial design (2(4)) based on an analysis of variance
      demonstrated that the pH, concentration of PAR, amount of dispersive and
      extraction solvents are statistically significant. Optimal condition for three
      variables: pH, concentration of PAR, amount of dispersive and extraction solvents
      are obtained by using Box-Behnken design. Under the optimum conditions, the
      calibration graphs are linear in the range of 20.0-350.0 ng mL(-1) with detection
      limit of 6.7 ng mL(-1) (3deltaB/slope) and the enrichment factor of this method
      for uranium reached at 135. The relative standard deviation (R.S.D.) is 1.64%
      (n=7, c=50 ng mL(-1)). The partial least squares (PLS) modeling was used for
      multivariate calibration of the spectrophotometric data. The orthogonal signal
      correction (OSC) was used for preprocessing of data matrices and the prediction
      results of model, with and without using OSC, were statistically compared. MA
      DLLME-OSC-PLS method was presented for the first time in this study. The root
      mean squares error of prediction (RMSEP) for uranium determination using PLS and
      OSC-PLS models were 4.63 and 0.98, respectively. This procedure allows the
      determination of uranium synthesis and real samples such as waste water with good
      reliability of the determination.

PMID- 25062052
TI  - A view of microstructure with technological behavior of waste incorporated
      ceramic bricks.
AB  - Production of ceramic bricks from mixtures of ceramic industry wastes (up to 50
      wt%) from the area of Vriddhachalam, Cuddalore district, Tamilnadu, India and
      kaolinitic clay from Thiruvananthapuram district, Kerala were investigated. The
      firing behavior of the ceramic mixtures was studied by determining their changes
      in mineralogy and basic ceramic properties such as water absorption, porosity,
      compressive strength and firing shrinkage at temperatures ranging from 900 to
      1200  degrees C in short firing cycles. The effect of the rejects addition
      gradually up to 50 wt% was analyzed with the variation of temperature on the
      mechanical properties and microstructure of the bricks. The highest compressive
      strength and lowest water absorption is observed for the sample with 40% rejects
      at 1100  degrees C which is supported by the results of SEM analysis. The
      resulting ceramic bricks exhibit features that suggest possibilities of using the
      ceramic rejects in the conventional brick making methods.

PMID- 25062053
TI  - Molecular structure, FT-IR, NBO, HOMO and LUMO, MEP and first order
      hyperpolarizability of (2E)-1-(2,4-Dichlorophenyl)-3-(3,4,5-trimethoxyphenyl)prop
      2-en-1-one by HF and density functional methods.
AB  - (2E)-1-(2,4-Dichlorophenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one is
      synthesized by using 2,4-dichloroacetophenone and 3,4,5-trimethoxybenzaldehyde in
      ethanol. The structure of the compound was confirmed by IR and single crystal X
      ray diffraction studies. FT-IR spectrum of (2E)-1-(2,4-dichloro-phenyl)-3-(3,4,5
      trimethoxyphenyl)prop-2-en-1-one was recorded and analyzed. The crystal structure
      is also described. The vibrational wavenumbers were computed using HF and DFT
      methods and are assigned with the help of potential energy distribution method.
      The first hyperpolarizability and infrared intensities are also reported. The
      geometrical parameters of the title compound obtained from XRD studies are in
      agreement with the calculated (DFT) values. The stability of the molecule arising
      from hyper-conjugative interaction and charge delocalization has been analyzed
      using NBO analysis. The HOMO and LUMO analysis are used to determine the charge
      transfer within the molecule. MEP was performed by the DFT method. From the MEP
      map of the title molecule, negative region is mainly localized over the
      electronegative oxygen atoms, in the carbonyl group and the oxygen atom O4 of the
      methoxy group and the maximum positive region is localized on the phenyl rings. 

PMID- 25062054
TI  - Synthesis, characterization and catalytic activity of Ag-acidfuchsin nanohybrid
      system towards the ring opening polymerization of epsilon-caprolactone.
AB  - The acidfuchsin (AF) decorated Ag nanoparticle (NP) was synthesized and its
      ability towards the ring opening polymerization (ROP) of epsilon-caprolactone
      (CL) was studied under N2 atmosphere at 160  degrees C in the presence of
      stannous octoate (SO) as a catalyst. Both the nanohybrid and nanocomposites were
      characterized by various analytical tools like Fourier transform infrared (FTIR)
      spectroscopy, UV-visible spectroscopy, nuclear magnetic resonance (NMR)
      spectroscopy, fluorescence spectroscopy, gel permeation chromatography (GPC),
      field emission scanning electron microscopy (FESEM), transmission electron
      microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). The number of
      binding site from the fluorescence spectrum confirmed that all the functional
      groups present in AF might have been involved in the ROP of CL.

PMID- 25062055
TI  - DNA-binding, topoisomerases I and II inhibition and in vitro cytotoxicity of
      ruthenium(II) polypyridyl complexes: [Ru(dppz)2L](2+) (L=dppz-11-CO2Me and dppz).
AB  - Two ruthenium(II) polypyridyl complexes, [Ru(dppz)2dppz-11-CO2Me](ClO4)2 (Ru1)
      and [Ru(dppz)3](ClO4)2 (Ru2), have been synthesized and characterized. The
      spectral characteristics of Ru1 and Ru2 were investigated by fluorescence
      spectroscopy and revealed that both complexes were sensitive to solvent polarity.
      The binding properties of the two complexes towards calf-thymus DNA (CT-DNA) have
      been investigated by different spectrophotometric methods and viscosity
      measurements, indicating that both complexes bind to CT-DNA by means of
      intercalation, but with different binding affinities. Topoisomerase inhibition
      and DNA strand passage assay demonstrates that the two complexes are dual
      inhibitors of topoisomerases I and IIa. On the other hand, the cytotoxicity of
      both complexes has been evaluated by MTT assays and Giemsa staining experiments.
      The main results reveal that the ester functional group has a significant effect
      on the DNA-binding affinities and topoisomerases inhibition effects of Ru1 and
      Ru2, and further advance our knowledge on the DNA-binding and topoisomerase
      inhibition by Ru(II) complexes. 

PMID- 25062056
TI  - Optimization of reaction conditions to fabricate nano-silver using Couroupita
      guianensis Aubl. (leaf & fruit) and its enhanced larvicidal effect.
AB  - Currently bioactive principles of plants and their nanoproducts have been
      extensively studied in agriculture and medicine. In this study Couroupita
      guianensis Aubl. leaf and fruit extracts were selected for rapid and cost
      effective synthesis of silver nanoparticles (leaf-LAgNPs and fruit-FAgNPs).
      Various physiological conditions such as temperature, pH, concentration of metal
      ions, stoichiometric proportion of reaction mixture and reaction time showed
      influence on the size, dispersity and synthesis rate of AgNPs. Generation of
      AgNPs was initially confirmed with the surface plasmon vibrations at 420 nm in UV
      visible spectrophotometer. The results recorded from X-ray diffractometer (XRD)
      and Transmission electron microscope (TEM) supports the biosynthesis of cubic
      crystalline LAgNPs & FAgNPs with the size ranges between 10-45 nm and 5-15 nm
      respectively. Surface chemistry of synthesized AgNPs was studied with Fourier
      transform infrared spectroscopy (FTIR), it reveals that water soluble phenolic
      compounds present in the extracts act as reducing and stabilizing agent. Leaf,
      fruit extracts and synthesized AgNPs were evaluated against IV instar larvae of
      Aedes aegypti (Diptera; Culicidae). Furthermore, different extracts and
      synthesized AgNPs showed dose dependent larvicidal effect against A. aegypti
      after 24h of treatment. Compare to all extracts such as ethyl acetate (leaf; LC50
      - 44.55 ppm and LC90 - 318.39 ppm & fruit; LC50 - 49.96 ppm and LC90 - 568.84 ppm
      respectively) and Methanol (leaf; LC50 - 85.75 ppm and LC90 - 598.63 ppm & fruit;
      LC50 - 67.78 ppm and LC90 - 714.45 ppm respectively) synthesized AgNPs showed
      extensive mortality rate (LAgNPs; LC50 - 2.1 ppm and LC90 - 5.59 ppm & FAgNPs;
      LC50 - 2.09 ppm and LC90 - 5.7 ppm). Hence, this study proves that C. guianensis
      is a potential bioresource for stable, reproducible nanoparticle synthesis
      (AgNPs) and also can be used as an efficient mosquito control agent.

PMID- 25062057
TI  - Synthesis and characterization of palladium nanoparticles using Catharanthus
      roseus leaf extract and its application in the photo-catalytic degradation.
AB  - The potential effect of Catharanthus roseus leaf extract for the formation of
      palladium nanoparticles and its application on dye degradation was discussed. The
      efficiency of C.roseus leaves are used as a bio-material for the first time as
      reducing agent. Synthesized palladium nanoparticles were supported by UV-vis
      spectrometry, XRD, FT-IR and TEM analysis. The secondary metabolites which are
      responsible for the formation of nanoparticles were identified by GC-MS. The
      results showed that effect of time was directly related to synthesized
      nanoparticles and functional groups has a critical role in reducing the metal
      ions and stabilizing the palladium nanoparticles in an eco-friendly process. 

PMID- 25062058
TI  - Comprehensive quantum chemical and spectroscopic (FTIR, FT-Raman, (1)H, (13)C
      NMR) investigations of (1,2-epoxyethyl)benzene and (1,2-epoxy-2-phenyl)propane.
AB  - Aromatic epoxides are causative factors for mutagenic and carcinogenic activity
      of polycyclic arenes. The 1,2- or 2,3-epoxy compounds are widely used to a
      considerable extent in the textile, plastics, pharmaceutical, cosmetics,
      detergent and photochemical industries. The FTIR and FT-Raman spectra of (1,2
      epoxyethyl)benzene and (1,2-epoxy-2-phenyl)propane are recorded in the regions
      4000-400 cm(-1) and 4000-100 cm(-1), respectively. The observed fundamentals are
      assigned to different normal modes of vibration. The structure of the compound
      has been optimised with B3LYP method using 6-311++G(**) and cc-pVTZ basis sets.
      The IR and Raman intensities are determined. The total electron density and
      molecular electrostatic potential surfaces of the molecule are constructed by
      using B3LYP/6-311++G(d,p) method to display electrostatic potential
      (electron+nuclei) distribution. The electronic properties HOMO and LUMO energies
      were measured. Natural bond orbital analysis of the compounds has been performed
      to indicate the presence of intramolecular charge transfer. The (1)H and (13)C
      NMR chemical shifts of the molecules have been analysed.

PMID- 25062059
TI  - Experimental and computational study on molecular structure and vibrational
      analysis of an antihyperglycemic biomolecule: gliclazide.
AB  - In present study, the experimental and theoretical harmonic vibrational
      frequencies of gliclazide molecule have been investigated. The experimental FT-IR
      (400-4000 cm(-1)) and Laser-Raman spectra (100-4000 cm(-1)) of the molecule in
      the solid phase were recorded. Theoretical vibrational frequencies and geometric
      parameters (bond lengths and bond angles) have been calculated using ab initio
      Hartree Fock (HF), density functional theory (B3LYP hybrid function) methods with
      6-311++G(d,p) and 6-31G(d,p) basis sets by Gaussian 09W program. The assignments
      of the vibrational frequencies were performed by potential energy distribution
      (PED) analysis by using VEDA 4 program. Theoretical optimized geometric
      parameters and vibrational frequencies have been compared with the corresponding
      experimental data, and they have been shown to be in a good agreement with each
      other. Also, the highest occupied molecular orbital (HOMO) and lowest unoccupied
      molecular orbital (LUMO) energies have been found.

PMID- 25062060
TI  - Spectroscopic studies on the interaction between novel polyvinylthiol
      functionalized silver nanoparticles with lysozyme.
AB  - Silver nanoparticles were functionalized with polyvinylthiol (Ag-PVT) and their
      effect on the conformation of hen-egg white lysozyme was seen by means of
      spectroscopic techniques, viz., UV visible, fluorescence (intrinsic and
      synchronous), resonance Rayleigh scattering and circular dichroism. UV absorption
      spectra of lysozyme show a hyperchromic shift on the addition of Ag-PVT
      nanoparticles indicating the complex formation between the two. The interaction
      between lysozyme and Ag-PVT nanoparticles was takes place via static quenching
      with 1:1 binding ratio as revealed by the analysis of fluorescence measurements.
      Circular dichroism spectroscopic data show a decrease in alpha-helical content of
      lysozyme on interaction with Ag-PVT nanoparticles which was due to the partial
      unfolding of the protein. Synchronous fluorescence spectroscopy disclosed that
      the microenvironments of both tryptophan and tyrosine residues were perturbed in
      the presence of Ag-PVT nanoparticles and perturbation in the tryptophan
      environment was more prominent. Rayleigh scattering (RRS) intensity increases on
      increasing the Ag-PVT nanoparticles concentration till it reaches to the
      saturation. The RRS intensity increases four times as compared to the native
      protein indicating the possibility of protein aggregation at higher
      concentrations of nanoparticles. 

PMID- 25062061
TI  - Role of irradiation in the green synthesis of silver nanoparticles mediated by
      fig (Ficus carica) leaf extract.
AB  - Biosynthesis of silver nanoparticles in an aqueous mixture of fig (Ficus carica)
      leaf extract and AgNO3 solution exposed to a set of irradiances at different
      wavelengths are studied. Nanoparticle formation for irradiances between 6.5
      mW/cm(2) and 13.3 mW/cm(2) in the 330-550 nm wavelength range is investigated and
      the results are compared to those of the nanoparticles synthesized in the dark
      and under direct sunlight. Ultraviolet-visible spectroscopy, Fourier-transform
      infrared spectroscopy and proton nuclear magnetic resonance spectroscopy, along
      with particle size analysis and transmission electron microscopy are employed for
      the characterization of samples and extracts. Irradiance is found to have
      profound influence on the reduction rates. However, size and spherical shape of
      the nanoparticles are persistent, irrespective of irradiance and wavelength.
      Irradiance is discussed to influence the particle formation and aggregation rates
      through the formation of free radicals in the fig extract.

PMID- 25062062
TI  - FT-IR, molecular structure, first order hyperpolarizability, NBO analysis, HOMO
      and LUMO and MEP analysis of 1-(10H-phenothiazin-2-yl)ethanone by HF and density
      functional methods.
AB  - FT-IR spectrum of 1-(10H-phenothiazin-2-yl)ethanone was recorded and analyzed.
      The equilibrium geometry, bonding features and harmonic vibrational wavenumbers
      were investigated with the help of HF and DFT methods. The normal modes are
      assigned with the help of potential energy distribution analysis. The observed
      vibrational wavenumbers were compared with the calculated results. The
      geometrical parameters of the title compound obtained from XRD studies are in
      agreement with the calculated (DFT) values. The first hyperpolarizability value
      is also reported. Natural bond orbital analysis confirms the presence of intra
      molecular charge transfer and hydrogen bonding interaction. The HOMO-LUMO gap
      explains the charge transfer interaction taking place within the molecule. The N
      H stretching frequency is red shifted in the IR spectrum with a strong intensity
      from the computed frequency, which indicates weakening of the N-H bond resulting
      in proton transfer to the neighboring units. From the MEP analysis it is evident
      that the negative charge covers the carbonyl and benzene and the positive region
      is over the NH group.

PMID- 25062063
TI  - Inconsistencies and misleading information in officially approved prescribing
      information from three major drug markets.
AB  - The summary of product characteristics (SPC) should provide information for the
      safe prescription and use of a drug. We evaluated the consistency of critical
      interaction warnings, the quality of presentation of undesirable effects as well
      as concordance of critical information of representative drugs marketed in the
      United States, the UK, and Germany. Reciprocal warnings regarding drug-drug
      interactions that constitute contraindications were frequently missing in the
      SPCs of the drugs concerned (all countries >40%). Most SPCs did not explicitly
      exclude adverse reactions considered not reasonably attributable to the use of
      the drug. Comparing SPCs of different generic brands of the same drug, only 60,
      10, and 20% of the US, UK, and German SPCs, respectively, provided identical
      contraindications. Current SPCs contain inconsistencies and misleading data that
      are not compatible with the purpose of SPCs, which is to provide a basis for the
      safe prescription and use of drugs. 

PMID- 25062064
TI  - Molecular docking simulations provide insights in the substrate binding sites and
      possible substrates of the ABCC6 transporter.
AB  - The human ATP-binding cassette family C member 6 (ABCC6) gene encodes an ABC
      transporter protein (ABCC6), primarily expressed in liver and kidney. Mutations
      in the ABCC6 gene cause pseudoxanthoma elasticum (PXE), an autosomal recessive
      connective tissue disease characterized by ectopic mineralization of the elastic
      fibers. The pathophysiology underlying PXE is incompletely understood, which can
      at least partly be explained by the undetermined nature of the ABCC6 substrates
      as well as the unknown substrate recognition and binding sites. Several
      compounds, including anionic glutathione conjugates (N-ethylmaleimide; NEM-GS)
      and leukotriene C4 (LTC4) were shown to be modestly transported in vitro;
      conversely, vitamin K3 (VK3) was demonstrated not to be transported by ABCC6. To
      predict the possible substrate binding pockets of the ABCC6 transporter, we
      generated a 3D homology model of ABCC6 in both open and closed conformation,
      qualified for molecular docking and virtual screening approaches. By docking 10
      reported in vitro substrates in our ABCC6 3D homology models, we were able to
      predict the substrate binding residues of ABCC6. Further, virtual screening of
      4651 metabolites from the Human Serum Metabolome Database against our open
      conformation model disclosed possible substrates for ABCC6, which are mostly
      lipid and biliary secretion compounds, some of which are found to be involved in
      mineralization. Docking of these possible substrates in the closed conformation
      model also showed high affinity. Virtual screening expands this possibility to
      explore more compounds that can interact with ABCC6, and may aid in understanding
      the mechanisms leading to PXE. 

PMID- 25062065
TI  - A sea change in exoplanet climate models?

PMID- 25062066
TI  - ITS polymorphisms shed light on hybrid evolution in apomictic plants: a case
      study on the Ranunculus auricomus complex.
AB  - The reconstruction of reticulate evolutionary histories in plants is still a
      major methodological challenge. Sequences of the ITS nrDNA are a popular marker
      to analyze hybrid relationships, but variation of this multicopy spacer region is
      affected by concerted evolution, high intraindividual polymorphism, and shifts in
      mode of reproduction. The relevance of changes in secondary structure is still
      under dispute. We aim to shed light on the extent of polymorphism within and
      between sexual species and their putative natural as well as synthetic hybrid
      derivatives in the Ranunculus auricomus complex to test morphology-based
      hypotheses of hybrid origin and parentage of taxa. We employed direct sequencing
      of ITS nrDNA from 68 individuals representing three sexuals, their synthetic
      hybrids and one sympatric natural apomict, as well as cloning of ITS copies in
      four representative individuals, RNA secondary structure analysis, and landmark
      geometric morphometric analysis on leaves. Phylogenetic network analyses indicate
      additivity of parental ITS variants in both synthetic and natural hybrids. The
      triploid synthetic hybrids are genetically much closer to their maternal
      progenitors, probably due to ploidy dosage effects, although exhibiting a
      paternal-like leaf morphology. The natural hybrids are genetically and
      morphologically closer to the putative paternal progenitor species. Secondary
      structures of ITS1-5.8S-ITS2 were rather conserved in all taxa. The observed
      similarities in ITS polymorphisms suggest that the natural apomict R. variabilis
      is an ancient hybrid of the diploid sexual species R. notabilis and the sexual
      species R. cassubicifolius. The additivity pattern shared by R. variabilis and
      the synthetic hybrids supports an evolutionary and biogeographical scenario that
      R. variabilis originated from ancient hybridization. Concerted evolution of ITS
      copies in R. variabilis is incomplete, probably due to a shift to asexual
      reproduction. Under the condition of comprehensive inter- and intraspecific
      sampling, ITS polymorphisms are powerful for elucidating reticulate evolutionary
      histories. 

PMID- 25062067
TI  - Frequency and correlates of maladaptive responses to paranoid thoughts in
      patients with psychosis compared to a population sample.
AB  - INTRODUCTION: The aims of this study were to identify whether responses to
      paranoid thoughts distinguish patients with psychotic disorders from people in
      the population who have paranoid thoughts occasionally and to identify factors
      that are associated with and might explain the different ways of responding.
      METHODS: Paranoid thoughts were assessed in patients diagnosed with a psychotic
      disorder (n = 32) and a population control sample (n = 34) with the Paranoia
      Checklist. Responses to paranoid thoughts were assessed with the Reactions to
      Paranoid Thoughts Scale (RePT) and social support, self-efficacy and cognitive
      insight were assessed as potential correlates of the responses to paranoid
      thoughts. RESULTS: The patients showed significantly more depressed, physical and
      devaluating responses to paranoid thoughts and employed less normalising
      responses than the controls. The differences in normalising responses were
      explained by perceived social integration, whereas the differences in depressive
      responses were explained by the overall levels of depression and partly explained
      by externality and social integration. CONCLUSIONS: Maladaptive responses to
      paranoid thoughts could be relevant to the pathogenesis and maintenance of
      persecutory delusions. Interventions aimed at reducing paranoia could benefit
      from targeting dysfunctional responses to paranoid thoughts and by placing a
      stronger emphasis on treating depression and improving social integration.

PMID- 25062069
TI  - The CER (Comparative Effectiveness Research) collaborative toolkit.

PMID- 25062068
TI  - A quantitative study of the relationship between the distribution of different
      types of collagen and the mechanical behavior of rabbit medial collateral
      ligaments.
AB  - The mechanical properties of ligaments are key contributors to the stability and
      function of musculoskeletal joints. Ligaments are generally composed of ground
      substance, collagen (mainly type I and III collagen), and minimal elastin fibers.
      However, no consensus has been reached about whether the distribution of
      different types of collagen correlates with the mechanical behaviors of
      ligaments. The main objective of this study was to determine whether the collagen
      type distribution is correlated with the mechanical properties of ligaments.
      Using axial tensile tests and picrosirius red staining-polarization observations,
      the mechanical behaviors and the ratios of the various types of collagen were
      investigated for twenty-four rabbit medial collateral ligaments from twenty-four
      rabbits of different ages, respectively. One-way analysis of variance was used in
      the comparison of the Young's modulus in the linear region of the stress-strain
      curves and the ratios of type I and III collagen for the specimens (the mid
      substance specimens of the ligaments) with different ages. A multiple linear
      regression was performed using the collagen contents (the ratios of type I and
      III collagen) and the Young's modulus of the specimens. During the maturation of
      the ligaments, the type I collagen content increased, and the type III collagen
      content decreased. A significant and strong correlation (R2 = 0.839, P < 0.05)
      was identified by multiple linear regression between the collagen contents (i.e.,
      the ratios of type I and type III collagen) and the mechanical properties of the
      specimens. The collagen content of ligaments might provide a new perspective for
      evaluating the linear modulus of global stress-strain curves for ligaments and
      open a new door for studying the mechanical behaviors and functions of connective
      tissues.

PMID- 25062070
TI  - Understanding and overcoming barriers to medication adherence: a review of
      research priorities.
AB  - Improving medication adherence has been identified as a crucial step towards
      improving health outcomes for patients with chronic disease and has provided the
      motivation for many changes in our health care system. Despite the volume of
      research done on this topic, however, we still lack important basic information
      about how to improve adherence in a cost-effective way. There is a need for a
      better understanding of what areas of research are most likely to produce
      advances that could be used by policymakers, providers, payers, or other
      stakeholders to generate real improvements in medication adherence. To address
      this, we developed a set of research priorities designed to improve understanding
      about whom to target for adherence interventions and which particular
      interventions to employ for specific subpopulations. To produce this research
      agenda, we synthesized information from the existing literature with a series of
      stakeholder interviews and expert panel meetings. We identified 6 key areas for
      research: (1) predicting nonadherence, (2) behavioral factors affecting
      nonadherence, (3) measuring the impact of nonadherence on health and cost
      outcomes, (4) effectiveness of existing interventions, (5) misaligned incentives
      between payers and providers, and (6) provider training and coordination of care.
      We provide detailed descriptions and example topics within each area.  As the
      health care system continues to embrace reforms designed to improve the value of
      care, more and better information is needed to guide efforts designed to improve
      medication adherence. Addressing the topic areas identified here will be an
      important step towards accomplishing this goal.  

PMID- 25062071
TI  - Medication monitoring and optimization: a targeted pharmacist program for
      effective and cost-effective improvement of chronic therapy adherence.
AB  - BACKGROUND: Community pharmacies provide a promising platform for monitoring
      and improving therapy adherence and providing pharmaceutical care. Structured
      methods and appropriate software are important tools to increase pharmacist
      effectiveness and improve health outcomes. In 2006, the Medication Monitoring and
      Optimization (MeMO) program was introduced in several community pharmacies in the
      Netherlands. MeMO facilitates targeted and continuous patient-centered
      pharmaceutical care around chronic medication, such as for osteoporosis,
      cardiovascular disease, and asthma/chronic obstructive pulmonary disease (COPD).
      OBJECTIVES: To describe the MeMO program and summarize findings from publications
      on its effectiveness, patient satisfaction, and cost-effectiveness.  METHODS: In
      the first part of this article, the MeMO program is extensively described. In the
      second part, a review of the evidence of effectiveness, cost-effectiveness, and
      patient satisfaction of the MeMO program is provided. Evidence is based on 5
      previously published articles. RESULTS: The MeMO program starts with structured
      counseling sessions with patients at the initiation and follow-up of chronic
      therapies. This process is followed by a continuous phase in which patients'
      therapy adherence is monitored on a monthly basis, using standardized search
      algorithms in the pharmacy database. When the algorithm detects a patient's
      discontinuation of therapy, tailored interventions are used to improve adherence
      and optimize pharmacotherapy. For osteoporosis patients, treatment
      discontinuation with bisphosphonates after 1 year dropped from 31.7% to 16.1% (P 
      less than  0.001). This program was shown to be cost-effective in patients
      initiating osteoporotic therapy. Future scenarios with lower drug prices (e.g.,
      from generic prescribing) result in cost savings for the MeMO program. For lipid
      lowering drugs, the MeMO program has been shown to lower therapy discontinuation
      after 1 year from 25.9% to 13.6% (P  less than  0.001). By extrapolating these
      results to patients' lifetimes, the intervention was estimated to be cost
      effective, with gains for primary prevention of cardiovascular events, and even
      cost saving in secondary prevention. Results from the ongoing MeMO asthma/COPD
      program are promising, showing marked improvements in therapy control and quality
      of life for asthma and COPD patients. Almost all patients participating in MeMO
      programs are satisfied with the pharmacy team and have gained knowledge of the
      effectiveness and administration of their medications and the importance of
      therapy adherence. CONCLUSION: The MeMO program is an effective and structured
      method to improve patients' adherence to chronic medication in the field of
      osteoporosis, lipid-lowering drugs, and asthma/COPD and is well received by
      patients. By targeting the program toward nonadherent and high-risk patients, the
      program showed favorable cost-effectiveness.

PMID- 25062072
TI  - Frequency and economic impact of comorbid cardiac conditions with multiple
      sclerosis.
AB  - BACKGROUND: Fingolimod, an oral immunomodulatory therapy approved to treat
      multiple sclerosis (MS) is contraindicated in patients with certain cardiac
      conditions, yet the frequency of these conditions in patients with MS is not
      known. This study assessed the frequency and economic impact of cardiac
      conditions among hospitalizations of patients with MS. OBJECTIVE: To determine
      the frequency and economic impact of selected comorbid cardiac conditions among
      hospitalizations of patients with a diagnosis of MS. METHODS: This was a
      retrospective, discharge-level cohort study of hospital discharge data from 2006
      2010. The frequencies of cardiac conditions of interest (based on
      contraindications to fingolimod in the prescribing information) were reported
      among all discharges with a diagnosis of MS. Two cohorts were defined: (1) MS
      with cardiac condition of interest and (2) MS with no cardiac condition of
      interest. The mean adjusted cost per discharge and incremental cost per hospital
      day were reported. RESULTS: Among 136,542 discharges with a diagnosis of MS, 9.2%
      (n = 12,504) had a comorbid cardiac condition of interest based on
      contraindications to fingolimod in the prescribing information. Heart failure
      (59.4%), myocardial infarction (17.2%), and occlusion of cerebral arteries
      (12.4%) were the most common cardiac conditions. The mean adjusted cost per
      discharge was significantly higher for the MS with cardiac condition cohort
      compared with the MS with no cardiac condition cohort ($17,623 vs. $11,663, P 
      less than  0.0001). The incremental cost per hospital day was $6,479 for the MS
      with cardiac condition cohort.  CONCLUSIONS: The presence of comorbid cardiac
      conditions among hospital discharges in patients with MS is substantial and
      associated with higher hospitalization costs. Health plans should give
      consideration to the overlapping presence of these diseases when determining
      coverage criteria for immunomodulatory therapies and designing clinical programs
      for MS.

PMID- 25062073
TI  - Use of an early disease-modifying drug adherence measure to predict future
      adherence in patients with multiple sclerosis.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) who are adherent to their
      treatment regimens are less likely to experience relapses and the cost associated
      with relapse. Pharmacists whose practice involves these specialty pharmaceuticals
      used to treat MS are striving for ways to improve outcomes by achieving treatment
      adherence in their patients. Specialty pharmacies have reported higher adherence
      rates than traditional pharmacies, which may translate to improved outcomes.
      Identifying patients who warrant increased adherence intervention is critical.
      Models using administrative health care claims to predict adherence have
      typically included demographic characteristics, comorbidities, and/or previous
      consumption of health care resources. Addition of a measure of early adherence
      may improve the ability to predict future adherence outcomes.  OBJECTIVE: To
      evaluate early adherence with disease-modifying drugs (DMDs) as a predictor of
      future adherence in patients with MS.  METHODS: The first DMD claim (i.e., index
      event) for adult MS patients (aged >=18 years and aged <= 65 years) who received
      self-injected DMDs between January 1, 2006, and May 31, 2010, was identified in a
      national U.S. managed care database. Patients were required to have continuous
      eligibility for 12 months pre- and 24 months post-index. Multiple regression
      models were used to predict future adherence as measured by the proportion of
      days covered (PDC). The base model included age, gender, a medication intensity
      measure, presence of a non-MS-related hospitalization pre-index, and markers for
      physical difficulty, forgetfulness, or depression/stress. Models adding early DMD
      adherence as a covariate were analyzed using incrementing 30-day periods
      predicting the subsequent 360 days.  RESULTS: There were 4,606 patients included
      with an average age of 46.0 (SD 9.4) years, and 78.7% were female. Average PDC in
      the first 360 days post-index was 80.0% (SD 26.0). Using the first 60 days of
      early adherence as the only predictor in the model showed an R2 of 20.6%. The
      base model (i.e., no early adherence measure but other covariates included)
      yielded an adjusted R2 of only 2.3%. As the time period of early adherence is
      increased (from 60 to 360 days), the explained variance as measured by adjusted
      R2 values increased from 20.6% to 53.5% (early adherence-only models). Addition
      of the covariates, other than early adherence, increased the R2 by 1% to 2%. 
      CONCLUSIONS: Statistical predictive models that include early adherence with DMDs
      were able to explain the variance in future adherence outcomes to a greater
      extent than models based solely on baseline characteristics. The efficiency of an
      adherence intervention in reaching its intended target can be improved by using
      models such as these with enhanced specificity and selectivity.

PMID- 25062074
TI  - Comparison of adherence rates for antiretroviral, blood pressure, or mental
      health medications for HIV-positive patients at an academic medical center
      outpatient pharmacy.
AB  - BACKGROUND: Despite advances in safety, tolerability, and decreased pill burden
      for human immunodeficiency virus (HIV) antiretroviral therapy (ART), nonadherence
      continues to be a major cause of HIV-related morbidity and mortality. Adherence
      to these medications presents particular challenges because persons living with
      HIV (PLWH) must use medication more consistently (>= 95%) than persons with other
      chronic diseases, such as hypertension or diabetes mellitus (>= 80%). OBJECTIVES:
      To (a) quantify PLWH adherence rates to scheduled ART, blood pressure
      medications, or mental health medications, (b) examine how pill burden and dosing
      schedule affected adherence, and (c) analyze a non-HIV comparator group for
      comparison with PLWH patients on adherence rates. METHODS: Patients >= 18 years
      of age, on any prescribed HIV ART, scheduled prescription blood pressure
      medication, or scheduled prescription mental health medication filled between
      March 1, 2012, and March 31, 2013, were included in the analysis of data from the
      University of Colorado Hospital outpatient pharmacy system. The proportion of
      days covered (PDC) was calculated to measure adherence. Statistical analyses were
      performed to compare adherence rates between groups. RESULTS: The study included
      865 PLWH, who filled 1,943 antiviral prescriptions with an average PDC of 84.5%.
      However, only 40% of patients had high enough adherence to achieve therapeutic
      benefits based on a criterion of at least 95% of scheduled doses taken. When
      separated by regimen, 282 patients filled single-tablet once-daily regimens; 295
      patients filled multitablet once-daily regimens; and 288 patients filled
      multitablet twice-daily regimens. The calculated PDC of PLWH on a single-tablet
      once-daily regimen was 89.7% versus 81.0% for PLWH on a multitablet once-daily
      regimen (P  less than  0.001). The average PDC for PLWH (n = 269) who filled 460
      scheduled blood pressure prescriptions was 82.7%. The average PDC for PLWH (n =
      295) filling 467 scheduled mental health prescriptions was 81.7%. This difference
      was statistically significant in adherence between ART and blood pressure
      medications of 2.5% (P = 0.013) and a difference between ART and scheduled mental
      health medications of 3.03% (P = 0.002). For the comparator group of similar
      patients without HIV, 895 patients filled 1,398 scheduled blood pressure
      medications, with an average adherence of 83.8%. The difference between groups
      was not statistically significant (P = 0.390). For scheduled mental health
      medications in the comparator group, there were 666 patients filling 828
      prescriptions. The comparator group had a higher average PDC than PLWH, with
      85.1% versus 81.7%, respectively (P = 0.009). CONCLUSIONS: Based on average PDC,
      PLWH filling prescriptions at the University of Colorado Hospital Infectious
      Disease Group Practice pharmacy had an adherence of 84.5% to ART. However, only
      40% of patients were adherent at the needed 95% level for therapeutic effects.
      Additionally, PLWH were more adherent to single-tablet once-daily regimens than
      to multitablet once-daily regimens or multitablet twice-daily regimens. Adherence
      in PLWH to HIV ART was better than the same patients' adherence to scheduled
      blood pressure and scheduled mental health medications. Levels of adherence still
      need to be improved to optimal to reduce rates of resistance and maximize
      therapeutic durability of selected regimens. When analyzed with the comparator
      group, adherence in PLWH to scheduled blood pressure medications was similar, but
      adherence to scheduled mental health medications was slightly worse. Further work
      is needed to address nonadherence among PLWH, including their adherence both to
      ART and to medications prescribed for other chronic diseases.

PMID- 25062075
TI  - Adherence to multiple medications prescribed for a chronic disease: a
      methodological investigation.
AB  - BACKGROUND: Many patients receive multiple medications for the treatment of a
      disease. While monitoring adherence is important, a composite measure of
      adherence is useful for estimating adherence to multiple medications in these
      patients. There are multiple ways to compute composite estimates of adherence to
      multiple medications, including (a) 80% of days covered by at least 1 medication
      ("at least 1"); (b) 80% of days covered by both medications ("both"); (c) 80% of
      days covered by each medication measured separately ("all"); and (d) computing an
      average of the individual medication adherence estimates ("average"). Comparison
      of adherence rates to individual medications and that of composite estimates are
      important for intervention decisions and effective disease management. 
      OBJECTIVES: To (a) examine adherence to multiple medications prescribed for a
      disease; (b) estimate composite adherence to multiple medications prescribed for
      a disease; and (c) determine the rate of differential classification of a patient
      being adherent as is estimated by different available algorithms.   METHODS: A
      retrospective cohort study was designed using 2002-2003 MarketScan Commercial
      Claims and Encounters data. To be included in the cohort, patients had to be less
      than aged 65 years and had to have separate prescriptions filled for 2 classes of
      diabetes medications (i.e., any sulfonylurea [SU] and any thiazolidinedione
      [TZD]) at least once; patients taking other diabetic medications over the
      observation period were excluded. Adherence was measured by proportion of days
      covered (PDC) over periods of 90 days (8 quarters total) and cumulatively over
      the 2-year study period. For some composite adherence estimates, patients were
      considered adherent if PDC >= 80%. Survival curves using the life-table method
      were constructed to compare the time until PDC became less than  80% as estimated
      by the 3 different categorical composite measures. RESULTS: A total of 6,043
      patients were included in the analysis. Across the 8 quarters under
      consideration, the average PDC estimates ranged between 69.8%-84.2% for SUs and
      70.3%-85.6% for TZDs. The mean composite PDC based on the average algorithm
      varied between 69.4% and 84.9% when measured over each quarter or cumulatively.
      Similarly, the rates of composite adherence ranged from 74.5% to 88.2%, 46.4% to
      61.2%, and 47.7% to 62.9% for the "at least 1," "both," and "all" methods,
      respectively. Many subjects were classified as adherent by 1 composite
      dichotomous measure but not by all 3 dichotomous measures (i.e., "all," "at least
      1," and "both"); of these patients, 30.6%-38.2% were classified differently as to
      their adherence status over different quarters by different measures. Survival
      curves of categorical composite measures were different (P  less than  0.05) from
      one another. "At least 1" identified more patients as persistent and showed a
      much slower decline than did the "all" or "both" approaches.  CONCLUSIONS:
      Subjects were found to have a level of adherence-as estimated by individual
      medication adherence and composite adherence metrics-for multiple medications
      prescribed for a disease that, while not optimal from the perspective of patient
      care, was not entirely poor. In addition, composite estimates of adherence
      considerably varied depending on algorithms used. Most importantly, a large
      number of patients appeared to be subject to inconsistent classification based on
      adherence measurement algorithm. Adherence estimates produced by different
      composite measurement approaches give rise to difficulty in consistent
      interpretation, which may be detrimental to appropriate patient care decision
      making.

PMID- 25062076
TI  - Store and prescription characteristics associated with primary medication
      nonadherence.
AB  - BACKGROUND: Primary medication nonadherence (PMN) is any instance whereby
      patients fail to initiate a pharmacotherapy regimen after receiving a
      prescription for new therapy. The Pharmacy Quality Alliance (PQA) has proposed a
      standardized definition for PMN and a quality measure to assess the rates of PMN
      in community pharmacies. OBJECTIVES: To (a) measure PMN using the proposed PQA
      measure with data available from a pharmacy dispensing system and (b) identify
      the prescription-level (patient, prescriber, and medication) and store-level
      (store and neighborhood) characteristics associated with PMN. METHODS: This study
      was approved by a southern university institutional review board, and a data use
      agreement was in place. A large national pharmacy grocery chain provided de
      identified, transactional data for 2010 through January 2012, for 100 pharmacies
      (de-identified unique patient and store codes were available). The proposed PQA
      PMN measure was used, and PMN rates were calculated. Investigators examined adult
      individuals with a new electronic prescription for any of the included
      medications during the measurement period and determined whether the medication
      or an appropriate alternative was claimed within 30 days. Multilevel logistic
      regression with a random intercept was used to evaluate prescription-level and
      store-level predictors of PMN. Prescription-level variables included prescriber
      type, PQA-defined drug class, patient gender and age, whether the prescription
      was accompanied by another prescription on the same day, payment source, and out
      of-pocket costs. A daily average prescription volume variable was calculated for
      each pharmacy as a store-level variable. Additional store-level variables were
      derived from the 2007-2011 American Community Survey, available from the U.S.
      Census Bureau (median household income, educational level, percentage of
      minorities, and percentage aged 65 years and over in the census tracts where the
      pharmacies are located).  RESULTS: Of the e-prescriptions during the 1-year
      measurement period, 29,238 were for new therapies as defined by the PMN measure,
      and 3,570 (12.2%) of those new prescriptions were not claimed within a 30-day
      period. There was significant variability among the pharmacies (intraclass
      correlation coefficient=0.140). In the adjusted multilevel model, the estimated
      odds of an unclaimed prescription were significantly different among drug classes
      comprising the PQA-PMN measure and were higher as out-of-pocket costs increased,
      when the prescription was accompanied by another prescription on the same day,
      and for primary care physicians relative to physician assistants and advanced
      practice nurses. The estimated odds were slightly higher for younger individuals,
      when originating at stores with lower prescription volumes and when originating
      at stores located in neighborhoods with higher household incomes. Although
      neither the gender of the patient nor the payment source were related to whether
      the prescription went unclaimed in the multivariable model, these variables,
      along with out-of-pocket costs and the accompaniment of the prescription with
      another prescription on the same day, were involved in cross-level interactions
      with household income and educational level.  CONCLUSIONS: This study is one of
      the first to use pharmacy prescription data to calculate PMN using the PQA
      standardized measure and to identify prescription-level and store-level factors
      associated with PMN. PMN remains a significant challenge in this setting, and
      there is significant variation in the outcome among pharmacies in the same chain,
      even after accounting for several potential store-level predictors. There is
      considerable opportunity for quality improvement to reduce the number of
      unclaimed prescriptions. Efforts directed at further understanding this behavior
      and how to design tailored interventions to reduce its occurrence are warranted.

PMID- 25062077
TI  - Geographic variation in medication adherence in commercial and Medicare part D
      populations.
AB  - BACKGROUND: Previous literature has emphasized the importance of cost sharing,
      health literacy, socioeconomic status, cognitive function, disease burden, and
      polypharmacy as some of the determinants of medication adherence. Little research
      has been published examining disparities in adherence rates when comparing
      different regions of the United States. OBJECTIVE: To examine the impact of
      geography, socioeconomic status, and other demographic variables on medication
      adherence rates in a large national sample of Medicare Part D and commercially
      insured beneficiaries. METHODS: This study focused on users of oral antidiabetic,
      antihypertensive, and/or antilipidemic medications. Beneficiaries who had at
      least 2 antidiabetic, antihypertensive, or antilipidemic prescription fills in
      2010, 2011, or 2012 and who were enrolled in a large commercial or Medicare Part
      D prescription drug plan for at least 80% of one of these years (9.6 months) were
      included in this study. Results were stratified by year and by benefit type.
      Logistic regression was used to test for the adherence differences among the 9
      U.S. regions as defined by the U.S. Census Bureau. Additional variables included
      in the model to control for population differences were age, gender,
      socioeconomic status, and yearly out-of-pocket medication expenses. RESULTS:
      After meeting all inclusion and exclusion criteria, 379,533 beneficiaries were in
      the 2012 Medicare cohort, and 659,553 beneficiaries were in the 2012 commercial
      cohort. New England was statistically the most adherent geographic region in both
      cohorts (Medicare odds ratio [OR] = 1.512, CI = 1.399-1.635); commercial OR =
      1.193, CI = 1.109-1.284). Younger age beneficiaries, lower income beneficiaries,
      and females were less adherent in both groups. CONCLUSIONS: In the commercial and
      Medicare populations, geography, socioeconomic status, age, and gender all impact
      the likelihood of a beneficiary being adherent to chronic medications for
      hypertension, diabetes, and hyperlipidemia. While this study does not elucidate
      the specific factors (i.e., health literacy, disease severity) driving geographic
      and other differences in medication adherence observed between groups, it does
      highlight the limitations of quality metrics and wellness initiatives that assume
      relative homogeneity in beneficiary characteristics across the United States.

PMID- 25062078
TI  - Concurrent use of comedications reduces adherence to antiretroviral therapy among
      HIV-infected patients.
AB  - BACKGROUND: The use of highly active antiretroviral therapy has significantly
      reduced morbidity and mortality, thus increasing life expectancy of human
      immunodeficiency virus (HIV)-infected individuals, transforming HIV into a
      chronic disease. Accordingly, there has been an increase in the number of
      comorbidities concomitantly present in these individuals and also an increased
      use of comedications, which may negatively impact antiretroviral therapy
      adherence. These factors can affect adherence to antiretroviral therapy. The role
      of the HIV clinical pharmacist is essential to achieve therapeutic objectives and
      enhance adherence. OBJECTIVE: To determine the influence of the comorbidities and
      comedications on antiretroviral therapy adherence among HIV-infected patients
      receiving services from a clinical pharmacist. METHODS: We conducted a
      prospective observational study that included HIV-infected outpatients who
      attended the pharmaceutical care office of a hospital pharmacy service, which
      initiated antiretroviral treatment between January 2002, and December 2011. The
      variables analyzed in the study were demographics (sex and age), HIV transmission
      mode, and the following variables at the time of comedication collection:
      hepatitis C virus or hepatitis B virus coinfection, HIV plasma viral load
      (copies/mL) and CD4+ T-cell count (cells/uL), Centers for Disease Control and
      Prevention HIV classification, number of hospital admissions and emergency room
      visits, and antiretroviral therapy-related features (type at baseline, treatment
      naive status, and number of changes since starting antiretroviral therapy). For
      follow-up at 12 months, antiretroviral therapy adherence was measured through
      pharmacy dispensing records and the Morisky Medication Adherence Scale (MMAS).
      Patients were considered adherent if antiretroviral therapy adherence through
      dispensing records was greater than 90%, and the MMAS score was 4. Other
      variables were number of comorbidities and number of comedications for other
      chronic diseases (non-HIV drugs). According to the number of comorbidities,
      patients were categorized as having multiple chronic conditions (polypathology)
      if they had 2 or more chronic diseases. Polypharmacy was defined specifically as
      the use of 5 or more prescription medications in a medication regimen. In
      addition, a complexity therapeutic index of antiretroviral therapy was calculated
      for each patient. We determined the risk of drug-related problems using the tool
      Predictor Index. To identify independent predictors of adherence to
      antiretroviral therapy, we performed a univariate logistic regression. Afterward,
      those variables that showed statistical significance in the univariate analysis
      and those with P  less than  0.25 were included in a multivariate model. The
      sample size was estimated by the Freeman equation. RESULTS: We included 594
      patients in the study (80.1% men, median age 47 years). In the univariate
      analysis, the variables that showed statistically significant relationships with
      antiretroviral therapy adherence were HIV transmission mode, detectable viral
      load, CD4+ T-cell count, AIDS-defining condition, hospital admission,
      antiretroviral therapy-naive treatment, type of antiretroviral therapy, high risk
      of drug-related problems, polypathology, and polypharmacy. Multivariate analysis
      showed that independent predictors of nonadherence to antiretroviral therapy were
      HIV transmission by intravenous drug use (OR = 0.56, 95% CI = 0.35-0.90),
      previous treatment with antiretroviral therapy (OR = 0.09, CI = 0.04-0.24),
      nontreatment changes (OR = 0.12, CI = 0.05-0.31), high risk of drug-related
      problems (OR = 0.38, CI = 0.23-0.63), and polypharmacy (OR = 0.36, CI = 0.21
      0.61). The value of the Hosmer and Lemeshow test confirmed the validity of this
      model (P = 0.378). CONCLUSIONS: Recently, the number of HIV-infected patients
      with polypharmacy has been higher, increasing the risk of nonadherence.
      Furthermore, previous treatment with antiretroviral therapy, HIV transmission by
      intravenous drug use, and high risk of drug-related problems are also associated
      with lower adherence.

PMID- 25062079
TI  - Association between dispensing channel and medication adherence among medicare
      beneficiaries taking medications to treat diabetes, high blood pressure, or high
      blood cholesterol.
AB  - BACKGROUND: Medication adherence, defined as taking medications as prescribed, is
      a key component in controlling disease progression and managing chronic illnesses
      such as diabetes, hypertension, and high blood cholesterol. These diseases
      constitute 3 of the top 5 most prevalent conditions among Medicare beneficiaries,
      warranting further attention to find ways to promote better medication adherence.
      The scientific literature has established the clinical and financial benefits of
      medication adherence and the role of dispensing channel in impacting adherence to
      medications. However, a common limitation in channel-adherence studies is the
      failure to control for healthy adherer effect (HAE), referring to individuals who
      are likely to engage proactively in activities that improve their adherence.
      Healthier individuals may choose the home-delivery channel to ensure continuity
      in their medication regimens and to minimize obstacles to adherence, such as
      inadequate access, inconvenience, and financial concerns. Thus, better medication
      adherence in home delivery may reflect healthier patients' predisposition to self
      select for home delivery options. To accurately attribute the impact of
      dispensing channel on adherence, research would need to control for bias from a
      patient's predisposition to be adherent.  OBJECTIVE: To examine the association
      of pharmacy dispensing channel (home delivery or retail pharmacy) with medication
      adherence for Medicare Part D beneficiaries taking medications for diabetes,
      hypertension, or high blood cholesterol, while controlling for low-income subsidy
      status, differences in days supply, and prior adherence behavior (PAB) as a way
      to partly control for HAE. METHODS: A retrospective analysis using de-identified
      pharmacy claims data from a large national pharmacy benefits manager between
      October 2010 and December 2012. Continuously eligible Medicare Part D
      beneficiaries (Medicare Advantage and prescription drug plans participants only)
      aged 65 years or older who had an antidiabetic, antihypertensive, or
      antihyperlipidemic prescription claim between October and December 2010, were
      identified and followed for the next 2 years. Those enrolled in a home delivery
      auto refill program were excluded from this analysis. Multivariate logistic
      regression was used to evaluate the impact of dispensing channel on medication
      adherence, controlling for differences in demographics, low-income subsidy
      status, disease burden, and drug-use pattern. Patients with a proportion of days
      covered of >= 80% were considered to be adherent. The analysis controlled for PAB
      by using patients' adherence status in the year 2011.  RESULTS: The final
      analytical samples consisted of 150,389 diabetic patients, 615,618 hypertension
      patients, and 358,795 high blood cholesterol patients. The adjusted odds of being
      adherent for beneficiaries using home delivery were 1.25 times higher (CI = 1.20
      1.30) for diabetes medications, 1.29 times higher (CI = 1.27-1.32) for
      hypertension medications, and 1.26 times higher (CI = 1.23-1.29) for high blood
      cholesterol medications, compared with beneficiaries using retail channels to
      obtain their prescriptions. PAB was the strongest contributor to the odds of a
      patient being adherent across all 3 therapy classes, ranging from odds ratio of
      4.48 to 8.09.  CONCLUSIONS: After excluding patients who received any
      prescriptions via home delivery auto refill programs and controlling for PAB,
      differences in days supply, low-income subsidy status, demographics, and disease
      burden, Medicare beneficiaries who use home delivery for antidiabetics,
      antihypertensives, or antihyperlipidemics have a greater likelihood of being
      adherent than patients who fill their prescriptions at retail. The results of
      this study provide evidence that where medications are received may impact
      adherence, even when controlling for PAB. Use of the home delivery dispensing
      channel may be an effective method to improve adherence for Medicare
      beneficiaries.

PMID- 25062080
TI  - Adherence and persistence to prescribed medication therapy among Medicare part D
      beneficiaries on dialysis: comparisons of benefit type and benefit phase.
AB  - BACKGROUND: The implementation of Medicare Part D provided insurance coverage for
      outpatient medications, but when persons reach the "gap," they have very limited
      or no medication insurance coverage until they reach a second threshold for
      catastrophic coverage. In addition, some patients have a low-income subsidy
      (LIS), and their out-of-pocket costs do not reach the threshold for the gap.
      Little is known about how these Part D types (LIS versus non-LIS) and benefit
      phases (before the gap, during the gap, after the gap) affect medication
      adherence and persistence of dialysis patients.  OBJECTIVE: To examine medication
      use, adherence, and persistence for Medicare-eligible dialysis patients by Part D
      benefit type and benefit phase.  METHODS: A retrospective cohort study using data
      from the U.S. Renal Data System (USRDS) was conducted for Medicare-eligible
      dialysis patients. Outcomes included medication use, adherence, and persistence.
      Patients were categorized into 4 cohorts based on their Part D benefit phase that
      the beneficiaries reached at the end of the year and LIS receipt in 2007: Cohort
      1 = non-LIS and did not reach the coverage gap; Cohort 2 = non-LIS and reached
      the coverage gap; Cohort 3 = non-LIS and reached catastrophic coverage after the
      gap; and Cohort 4 = received an LIS and none of the LIS patients reached the
      coverage gap. Outcomes were measured separately for 5 therapeutic classes of
      outpatient prescription drugs: antihyperglycemics, antihypertensives,
      antilipidemics, phosphate binders, and calcimimetics.  RESULTS: A total of 11,732
      patients met the study inclusion criteria. Patients were distributed among the
      cohorts as follows: 3,678 (31.3%) patients in Cohort 1 who did not reach the
      coverage gap; 4,349 (37.1%) patients in Cohort 2 who reached the coverage gap but
      not catastrophic coverage; 1,310 (11.2%) patients in Cohort 3 who reached
      catastrophic coverage; and 2,395 (20.4%) patients in Cohort 4 who had an LIS
      (none of whom reached the gap). Overall, the percentage of patients who were
      adherent to their medications (>= 80% medication possession ratio) was low: 39%
      for antihyperglycemics, 59% for antihypertensives, 54% for antilipidemics, 22%
      for phosphate binders, and 35% for cinacalcet. There were wide ranges in
      adherence rates depending on the cohort. For patients on antihyperglycemics,
      antihypertensives, antilipidemics, phosphate binders, and cinacalcet, the odds
      ratios for adherence to therapy were 0.76 (95% C I =0.63-0.92), 1.06 (0.94-1.19),
      0.80 (0.67-0.95), 0.65 (0.55-0.76), and 0.39 (0.30-0.49), respectively; the
      hazard ratios for discontinuation of therapy were 1.18 (95% CI 1.06-1.31), 1.01
      (0.93-1.10), 1.25 (1.12-1.40), 1.13 (1.05-1.21), and 1.61 (1.75-1.82),
      respectively, for Cohort 2 patients who reached the coverage gap compared with
      those in Cohort 4 who received an LIS. In addition, when comparing adherence
      before and after the benefit gap, patients in Cohort 2 were significantly more
      likely to be nonadherent to medications for diabetes (relative risk (RR) = 1.71,
      95% CI = 1.48-1.99), hypertension (RR = 1.69, 95% CI = 1.54-1.85), hyperlipidemia
      (RR = 2.01, 95% CI = 1.76-2.29), hyperphosphatemia (RR = 1.74, 95% CI = 1.55
      1.95), and hyperparathyroidism (RR = 2.08, 95% CI = 1.66-2.60) after reaching the
      coverage gap.  CONCLUSIONS: More than half of Medicare beneficiaries on dialysis
      reached the Part D coverage gap in 2007. Our findings suggest that the Part D
      coverage gap was significantly associated with decreases in adherence and
      persistence for medications frequently used in patients undergoing dialysis.
      Patients who reached the coverage gap (Cohort 2) often decreased use of or
      discontinued critical medications after reaching the coverage gap. Compared with
      patients who had an LIS (Cohort 4), patients in Cohort 2 had significantly lower
      medication adherence and persistence levels. The negative impact of the Part D
      coverage gap (high out-of-pocket cost sharing) on medication adherence and
      persistence for Medicare-eligible dialysis patients has implications for
      currently proposed Medicare end-stage renal disease bundled reimbursement payment
      and requires more research.

PMID- 25062081
TI  - Do apolipoproteins improve coronary risk prediction in subjects with metabolic
      syndrome? Insights from the North Italian Brianza cohort study.
AB  - OBJECTIVE: We assessed predictive abilities and clinical utility of CVD risk
      algorithms including ApoB and ApoAI among non-diabetic subjects with metabolic
      syndrome (MetS). METHODS: Three independent population-based cohorts (3677 35-74
      years old) were enrolled in Northern Italy, adopting standardized MONICA
      procedures. Through Cox models, we assessed the associations between lipid
      measures and first coronary events, as well as the changes in discrimination and
      reclassification (NRI) when standard lipids or apolipoproteins were added to the
      CVD risk algorithm including non-lipids risk factors. Finally, the best models
      including lipids or apolipoproteins were compared. RESULTS: During the 14.5 years
      median follow-up time, 164 coronary events were validated. All measures showed
      statistically significant associations with the endpoint, while in the MetS
      subgroup HDL-C and ApoAI (men, HR = 1.59; 95%CI: 0.96-2.65) were not associated.
      Models including HDL-C plus TC and ApoB plus ApoAI for lipids and
      apolipoproteins, respectively, showed the best predictive values. When ApoB plus
      ApoAI replaced TC plus HDL-C, NRI values improved in subjects with MetS (13.8;
      CI95%: -5.1,53.1), significantly in those previously classified at intermediate
      risk (44.5; CI95% 13.8,129.6). In this subgroup, 5.5% of subjects was moved in
      the high (40.0% of expected events) and 17.0% in the low risk class (none had an
      event at 10 years). CONCLUSIONS: ApoB and ApoAI could improve coronary risk
      prediction when used as second level biomarkers in non-diabetic subjects with
      MetS classified at intermediate risk. The absence of cases moved downward
      suggests the gain in avoiding treatments in non-cases and favor the use of
      apolipoproteins for risk assessment.

PMID- 25062083
TI  - Placental lesions of vascular insufficiency are associated with anti-angiogenic
      state in women with preeclampsia.
AB  - OBJECTIVE: To evaluate if placental histopathological changes of vascular
      insufficiency correlate with circulating angiogenic factors in patients with
      preeclampsia. MATERIALS AND METHODS: Subjects were selected from a previous
      prospective cohort study of preeclampsia based on the availability of plasma anti
      angiogenic factor (sFlt1) and pro-angiogenic factor (PlGF) measurements and
      placental histology specimens. Preeclamptic patients were divided into two groups
      based on plasma levels of these factors described as a ratio: anti-angiogenic
      preeclampsia with sFlt1/PlGF ratio >=85 and normal angiogenic preeclampsia with
      sFlt1/PlGF < 85. The placental lesions of vascular insufficiency that were
      studied specifically included atherosis, infarcts, syncytial knots, acute and
      chronic abruption, hematoma, and fetal thrombosis. The data are shown as median
      (quartile 1 and quartile 3) or n (%) when appropriate. RESULTS: The anti
      angiogenic preeclampsia group (N = 48) presented at an earlier gestational age
      (weeks) than the normal angiogenic group (N = 28); {32 (28, 34) versus 35 (32,
      36), p = 0.002}, had higher systolic blood pressure (mmHg) {154 (147, 168) versus
      147 (132, 158), p = 0.02}, delivered early (weeks) {(32 (29, 34) versus 36 (34,
      37), p < 0.001} and had lower birth weight (grams) {(1550 (1055, 2060) versus
      2655 (2285, 3343), p < 0.001}. Several pathologic lesions were found
      significantly more often in the anti-angiogenic preeclampsia group; atherosis
      {27.7% versus 3.6%, p < 0.05}, infarcts {58.3% versus 3.6%, p = 0.002}, and
      syncytial knots {81.3% versus 39.3%, p < 0.001}. CONCLUSION: Preeclamptic
      patients with imbalance in circulating angiogenic factors have disproportionally
      higher rates of placental vascular lesions historically associated with severe
      disease.

PMID- 25062082
TI  - Redox proteomics changes in the fungal pathogen Trichosporon asahii on arsenic
      exposure: identification of protein responses to metal-induced oxidative stress
      in an environmentally-sampled isolate.
AB  - Trichosporon asahii is a yeast pathogen implicated in opportunistic infections.
      Cultures of an isolate collected from industrial wastewater were exposed for 2
      days to 100 mg/L sodium arsenite (NaAsO2) and cadmium (CdCl2). Both metals
      reduced glutathione transferase (GST) activity but had no effect on superoxide
      dismutase or catalase. NaAsO2 exposure increased glutathione reductase activity
      while CdCl2 had no effect. Protein thiols were labeled with 5-iodoacetamido
      fluorescein followed by one dimensional electrophoresis which revealed extensive
      protein thiol oxidation in response to CdCl2 treatment but thiol reduction in
      response to NaAsO2. Two dimensional electrophoresis analyses showed that the
      intensity of some protein spots was enhanced on treatment as judged by SameSpots
      image analysis software. In addition, some spots showed decreased IAF
      fluorescence suggesting thiol oxidation. Selected spots were excised and tryptic
      digested for identification by MALDI-TOF/TOF MS. Twenty unique T. asahii proteins
      were identified of which the following proteins were up-regulated in response to
      NaAsO2: 3-isopropylmalate dehydrogenase, phospholipase B, alanine-glyoxylate
      aminotransferase, ATP synthase alpha chain, 20S proteasome beta-type subunit
      Pre3p and the hypothetical proteins A1Q1_08001, A1Q2_03020, A1Q1_06950,
      A1Q1_06913. In addition, the following showed decreased thiol-associated
      fluorescence consistent with thiol oxidation; aconitase; aldehyde reductase I;
      phosphoglycerate kinase; translation elongation factor 2; heat shock protein 70
      and hypothetical protein A1Q2_04745. Some proteins showed both increase in
      abundance coupled with decrease in IAF fluorescence; 3-hydroxyisobutyryl-CoA
      hydrolase; homoserine dehydrogenase Hom6 and hypothetical proteins A1Q2_03020 and
      A1Q1_00754. Targets implicated in redox response included 10 unique metabolic
      enzymes, heat shock proteins, a component of the 20S proteasome and translation
      elongation factor 2. These data suggest extensive proteomic alterations in
      response to metal-induced oxidative stress in T. asahii. Amino acid metabolism,
      protein folding and degradation are principally affected.

PMID- 25062084
TI  - Dengue virus transmission by blood stem cell donor after travel to Sri Lanka;
      Germany, 2013.
AB  - Three days after donation of peripheral blood stem cells to a recipient with
      acute myeloblastic leukemia, dengue virus was detected in the donor, who had
      recently traveled to Sri Lanka. Transmission to the recipient, who died 9 days
      after transplant, was confirmed. 

PMID- 25062086
TI  - Mandibular function after Myorelaxation Therapy in temporomandibular disorders.
AB  - PURPOSE: The aim of this study was to analyze the efficacy of Myorelaxation
      Therapy in temporomandibular disorders on the basis of mandibular movement
      measurements, reported functional impairment and clinical findings.
      MATERIAL/METHODS: To ascertain the mandibular movements 78 women were
      investigated. The first group consisted of 32 consecutive patients (23.3+/-4.8
      years) suffering from muscle disorder and disk displacement with a reduction
      serving as a treated group. The second group was formed from 46 volunteers, as a
      healthy group (20.1+/-1.3 years). Jaw-tracking records (K7, Myotronics-Noromed
      Inc.) were performed including the measurements of opening, lateral and
      protrusive movement range, maximal and average velocity of opening/closing.
      Reported impairment and clinical data were collected. The treatment involved
      nocturnally applied a non-occluding sublingual relaxation splint combined with
      daily performed stretching exercises. Measurements were taken before treatment,
      after 4 weeks with no interventions (control period) and after 3 weeks, 3 and 6
      months. RESULTS: After the treatment mandibular opening range increased by 8mm
      (19%, p<0.05), lateral movement by 2.1mm (36%, p<0.05) while protrusive movement
      decreased by 0.5mm (p>0.05). Maximal and average velocity parameters
      significantly increased (p>0.05). These results were supported by the decrease in
      reported impairment and clinical pain occurrence (p<0.05). Only joint clicking
      change was non-significant (p>0.05). CONCLUSIONS: Myorelaxation Therapy was
      effective in the treatment of our group of patients. A significant improvement in
      the opening and lateral movement range, as well as opening/closing velocity was
      obtained after 6 months of treatment. This method can be easily managed by
      general practitioner, especially in muscles-related TMD types.

PMID- 25062085
TI  - Serological association of Chlamydia pneumoniae infection with age-related
      macular degeneration: a systematic review and meta-analysis.
AB  - BACKGROUND: We investigated the serological association of Chlamydia pneumoniae
      infection with age-related macular degeneration (AMD). METHODS: A systematic
      review and meta-analysis was performed. PubMed, Embase, Web of Science and the
      Association of Research in Vision and Ophthalmology abstracts were searched to
      identify studies investigating the serological association of Chlamydia
      pneumoniae infection with age-related macular degeneration. The quality of
      original studies was assessed using the Newcastle-Ottawa scale. Heterogeneity was
      explored with meta-regression. The odds ratios (ORs) and standardized mean
      differences (SMD) of Chlamydia pneumoniae infection between AMD patients and
      controls were pooled. RESULTS: In total, 9 studies met the inclusion criteria
      using the Newcastle-Ottawa scale scores ranging from 4 to 9. There was
      heterogeneity among studies due to a difference in the study designs and
      measurement of exposure to Chlamydia pneumoniae infection. The overall OR of
      Chlamydia pneumoniae infection with AMD was 1.11 (95% confidence interval: 0.78
      1.57, P = 0.56). The overall SMD of antibody titer between AMD and control was
      0.43 (95% confidence interval: -0.12 to 0.99, P = 0.13). CONCLUSIONS: Evidence
      from the current published literature suggested no statistically significant
      association between Chlamydia pneumoniae infection and AMD.

PMID- 25062087
TI  - A lysosome-targeted drug delivery system based on sorbitol backbone towards
      efficient cancer therapy.
AB  - A straightforward synthetic approach was adopted for the construction of a
      lysosome-targeted drug delivery system (TDDS) using sorbitol scaffold (Sor)
      linked to octa-guanidine and tetrapeptide GLPG, a peptide substrate of lysosomal
      cysteine protease, cathepsin B. The main objective was to efficiently deliver the
      potential anticancer drug, doxorubicin to the target sites, thereby minimizing
      dose-limiting toxicity. Three TDDS vectors were synthesized viz., DDS1: Sor-GLPG
      Fl, DDS2: Sor-Fl (control) and DDS3: Sor-GLPGC-SMCC-Dox. Dox release from DDS3 in
      the presence of cathepsin B was studied by kinetics measurement based on the
      fluorescent property of Dox. The cytotoxicity of DDS1 was assessed and found to
      be non-toxic. Cellular internalization and colocalization studies of all the 3
      systems were carried out by flow cytometry and confocal microscopy utilizing
      cathepsin B-expressing HeLa cells. DDS1 and DDS3 revealed significant
      localization within the lysosomes, in contrast to DDS2 (control). The doxorubicin
      conjugated carrier, DDS3, demonstrated significant cytotoxic effect when compared
      to free Dox by MTT assay and also by flow cytometric analysis. The targeted
      approach with DDS3 is expected to be promising, because it is indicated to be
      advantageous over free Dox, which possesses dose-limiting toxicity, posing risk
      of injury to normal tissues. 

PMID- 25062089
TI  - Anthropology, ethical dissonance, and the construction of the object.
AB  - In this article, I discuss certain questions relating to the ethical difficulties
      faced by anthropologists when dealing with two different social groups and when
      one group holds a position of dominance over the other. In the first example, I
      draw on my work on doctor-patient relationships in France; in the second, on a
      study on reproduction in immigrant African families from Mali and Senegal, living
      in polygynous households in France. I use these examples to explore questions of
      positionality, beneficence, and potential harm. I show the choices I made in
      order to construct an epistemologically ethical object. 

PMID- 25062088
TI  - IGF-1 regulates Cyr61 induced breast cancer cell proliferation and invasion.
AB  - BACKGROUND: Studies from our laboratory and others have shown that cysteine-rich
      61 (Cyr61) may be involved in tumor proliferation and invasion. In earlier
      studies, we demonstrated increased insulin-like growth factor-I (IGF-1) is
      associated with breast tumor formation and poor clinical outcomes. In our current
      study we have investigated IGF-1 regulation of Cyr61 and whether targeting IGF-1
      could inhibit Cyr61 induced tumor growth and proliferation. METHODS: Several ATCC
      derived normal and breast cancer cell lines were used in this study: MDA-MB231,
      BT474, MCF-7, and SKBR3. We also tested cells stably transfected in our
      laboratory with active Akt1 (pAkt; SKBR3/AA and MCF-7/AA) and dominant negative
      Akt1 (SKBR3/DN and MCF-7/DN). In addition, we used MCF-7 cells transfected with
      full length Cyr61 (CYA). Monolayer cultures treated with IGF-1 were analyzed for
      Cyr61 expression by RT-PCR and immunohistochemical staining. Migration assays and
      MTT based proliferation assays were used to determine invasive characteristics in
      response to IGF-1/Cyr61 activation. RESULTS: Cells with activated Akt have
      increased levels of Cyr61. Conversely, cells with inactive Akt have decreased
      levels of Cyr61. IGF-1 treatment increased Cyr61 expression significantly and
      cells with high level of Cyr61 demonstrate increased invasiveness and
      proliferation. Cyr61 overexpression and activation led to decrease in E-cadherin
      and decrease in FOXO1. Inhibition of the PI3K and MAPK pathways resulted in
      significant decrease in invasiveness and proliferation, most notably in the PI3K
      pathway inhibited cells. CONCLUSION: The findings of this study show that IGF-1
      upregulates Cyr61 primarily through activation of the Akt-PI3K pathway. IGF-1
      induced MAPK plays a partial role. Increase in Cyr61 leads to increase in breast
      cancer cell growth and invasion. Hence, targeting Cyr61 and associated pathways
      may offer an opportunity to inhibit IGF-1 mediated Cyr61 induced breast cancer
      growth and invasion.

PMID- 25062090
TI  - Laparoscopic salpingotomy using the floseal hemostatic sealant in patients with
      tubal pregnancy.
AB  - BACKGROUND: To present our initial experience with laparoscopic salpingotomy
      using the FlosealTM (Baxter International Corp., Deerfield, IL) hemostatic matrix
      for tubal pregnancy and to evaluate the efficacy and tubal patency after
      salpingotomy. MATERIALS AND METHODS: A prospective study was conducted on 20
      consecutive patients with tubal pregnancy undergoing laparoscopic salpingotomy
      using the Floseal hemostatic matrix. The outcome measures were treatment success
      rates and homolateral patency rates. RESULTS: Of 20 cases, 19 cases (95%) were
      successfully performed without any additional intervention, and 1 case was
      switched to salpingectomy during the initial surgery. During the mean beta-human
      chorionic gonadotropin resolution time of 17.9+/-6.4 days, postoperative
      complications or persistent trophoblasts did not occur. Of 19 salpingotomy
      patients, only 12 patients received a tubal patency test using
      hysterosalpingography, and the homolateral tubal patency rate was 75% (9 of 12).
      CONCLUSIONS: The use of Floseal allows laparoscopic salpingotomy to be performed
      successfully and easily with comparable outcomes.

PMID- 25062091
TI  - Systematic review of strategies to increase men's HIV-testing in sub-Saharan
      Africa.
AB  - OBJECTIVE: This systematic review summarizes evidence on the effectiveness of
      strategies to increase men's HIV-testing in sub-Saharan Africa. METHODS: Medline,
      EmBase, Africa-Wide Information and Global Health were searched. Cluster and
      individually randomized trials evaluating interventions to increase the
      proportion of adults (>= 15 years) testing for HIV were eligible if they were
      conducted in sub-Saharan Africa, included men in the study population, and
      reported HIV-testing data by sex. References were independently screened.
      RESULTS: Of the 1852 references, 15 papers including 16 trials were eligible.
      Trials were judged too heterogeneous to combine in meta-analysis. Three
      interventions invited men to attend antenatal care-based HIV-testing via pregnant
      partners, of which two showed a significant effect on partner-testing. One
      intervention invited men to HIV-test through pregnant partners and showed an
      increase in HIV-testing when it was offered in bars compared with health
      facilities. A trial of notification to partners of newly diagnosed HIV-positive
      patients showed an increase in testing where notification was by healthcare
      providers compared with notification by the patient. Three interventions reached
      men already at health facilities and eight reported the effects of community
      based HIV testing. Mobile-testing had a significant effect on HIV-testing
      compared with standard voluntary counselling and testing. Home-based testing also
      had a significant effect, but reached smaller numbers of men than mobile-testing.
      DISCUSSION: Interventions to encourage HIV-testing can increase men's levels of
      HIV testing. Community-based programmes in particular had a large effect on
      population levels of HIV-testing. More data on costs and potential population
      impact of these approaches over different time-horizons would aid policy-makers
      in planning resource allocation to increase male HIV-testing.

PMID- 25062093
TI  - Manganese-substituted rare-earth zinc arsenides RE(1-y)Mn(x)Zn(2-x)As2 (RE = Eu
      Lu) and RE(2-y)Mn(x)Zn(4-x)As4 (RE = La-Nd, Sm, Gd).
AB  - Two series of Mn-substituted rare-earth zinc arsenides RE(1-y)Mn(x)Zn(2-x)As2 (RE
      = Eu-Lu) and RE(2-y)Mn(x)Zn(4-x)As4 (RE = La-Nd, Sm, Gd) were prepared by
      reaction of the elements at 750  degrees C. Both series are derived from ideal
      empirical formula REM2As2 (M = Mn, Zn) and adopt crystal structures related to
      the trigonal CaAl2Si2-type (space group P3m1) in which hexagonal nets of RE atoms
      and [M2As2] slabs built up of edge-sharing M-centered tetrahedra are alternately
      stacked along the c-direction. For compounds with divalent RE components (Eu,
      Yb), the fully stoichiometric and charge-balanced formula REM2As2 is obtained,
      with Mn and Zn atoms statistically disordered within the same tetrahedral site.
      For compounds with trivalent RE components, the RE sites become deficient, and
      the Mn atoms are segregated from the Zn atoms in separate tetrahedral sites.
      Within the series RE(1-y)Mn(x)Zn(2-x)As2 (Gd-Tm, Lu), the parent CaAl2Si2-type
      structure is retained, and the Mn atoms are disordered within partially occupied
      interstitial sites above and below [Zn(2-x)As2] slabs. Within the series RE(2
      y)Mn(x)Zn(4-x)As4 (RE = La-Nd, Sm, Gd), the c-axis becomes doubled as a result of
      partial ordering of Mn atoms between every other pair of [Zn(2-x)As2] slabs.
      Attempts to synthesize Gd-containing solid solutions with the charge-balanced
      formula Gd0.67Mn(x)Zn(2-x)As2 suggested that these phases could be formed with up
      to 50% Mn substitution. Band structure calculations reveal that a hypothetical
      superstructure model with the formula La1.33MnZn3As4 would have no gap at the
      Fermi level and that slightly lowering the electron count alleviates antibonding
      Mn-As interactions; a spin-polarized calculation predicts nearly ferromagnetic
      half-metallic behavior. X-ray photoelectron spectroscopy confirms the presence of
      divalent Mn in these compounds.

PMID- 25062092
TI  - Renal epithelial cells produce and spread HIV-1 via T-cell contact.
AB  - OBJECTIVES: Increasing evidence supports the role of the kidney as a reservoir
      for HIV-1. In-vitro co-cultivation of HIV-infected T cells with renal tubule
      epithelial (RTE) cells results in virus transfer to the latter, whereas cell-free
      virus infection is inefficient. We further characterized the fate of HIV-1 after
      it is internalized in renal epithelial cells. METHODS: Primary or immortalized
      CD4 cells were infected with a green fluorescent protein (GFP)-expressing
      replication competent HIV-1. HIV-1 transfer from T cells to RTE cells was carried
      out in a co-culture system and evaluated by fluorescence-activated cell sorting
      analysis. HIV-1 integration in renal cells was evaluated by Alu-PCR and the
      production of infectious particles was assessed by p24-ELISA and TZM-bl assay.
      HIV-infected renal cells were used as donor cells in a co-culture system to
      evaluate their ability to transfer the virus back to T cells. RESULTS: Renal
      cells become productively infected by HIV-1 and multiple copies of HIV-1 can be
      transferred from infected T cells to renal cells. Two separate cell populations
      were identified among infected renal cells based on reporter gene GFP expression
      level (low vs. high), only the high showing sensitivity to azidothymidine and
      ritonavir. Co-cultivation of HIV-1-infected renal cells with noninfected T cells
      resulted in HIV-1 transmission to T cells, supporting bidirectional exchange of
      virus between T cells and kidney-derived cells. Persistent expression and
      generation of infectious virus in renal cells required HIV integration.
      CONCLUSION: These results support the kidney as a potential reservoir where virus
      is exchanged between interstitial T cells and RTE cells.

PMID- 25062094
TI  - Modulating the electronic structure of chromophores by chemical substituents for
      efficient energy transfer: application to fluorone.
AB  - Strong electron correlation within a quasi-spin model of chromophores was
      recently shown to enhance exciton energy transfer significantly. Here we
      investigate how the modulation of the electronic structure of the chromophores by
      chemical substitution can enhance energy-transfer efficiency. Unlike previous
      work that does not consider the direct effect of the electronic structure on
      exciton dynamics, we add chemical substituents to the fluorone dimer to study the
      effect of electron-donating and electron-withdrawing substituents on exciton
      energy transfer. The exciton dynamics are studied from the solution of a quantum
      Liouville equation for an open system whose model Hamiltonian is derived from
      excited-state electronic structure calculations. Both van der Waals energies and
      coupling energies, arising from the Hellmann-Feynman force generated upon
      transferring the dimers from infinity to a finite separation, are built into the
      model Hamiltonian. Though these two effects are implicitly treated in dipole
      based models, their explicit and separate treatment as discussed here is critical
      to forging the correct connection with the electronic structure calculations. We
      find that the addition of electron-donating substituents to the fluorone system
      results in an increase in exciton-transfer rates by factors ranging from 1.3-1.9.
      The computed oscillator strength is consistent with the recent experimental
      results on a larger heterodimer system containing fluorone. The oscillator
      strength increases with the addition of electron-donating substituents. Our
      results indicate that the study of chromophore networks via electronic structure
      will help in the future design of efficient synthetic light-harvesting systems. 

PMID- 25062096
TI  - Functional classifications for cerebral palsy: correlations between the gross
      motor function classification system (GMFCS), the manual ability classification
      system (MACS) and the communication function classification system (CFCS).
AB  - This study aimed to investigate a possible correlation between the gross motor
      function classification system-expanded and revised (GMFCS-E&R), the manual
      abilities classification system (MACS) and the communication function
      classification system (CFCS) functional levels in children with cerebral palsy
      (CP) by CP subtype. It was also geared to verify whether there is a correlation
      between these classification systems and intellectual functioning (IF) and
      parental socio-economic status (SES). A total of 87 children (47 males and 40
      females, age range 4-18 years, mean age 8.9+/-4.2) were included in the study. A
      strong correlation was found between the three classifications: Level V of the
      GMFCS-E&R corresponds to Level V of the MACS (rs=0.67, p=0.001); the same
      relationship was found for the CFCS and the MACS (rs=0.73, p<0.001) and for the
      GMFCS-E&R and the CFCS (rs=0.61, p=0.001). The correlations between the IQ and
      the global functional disability profile were strong or moderate (GMFCS and IQ:
      rs=0.66, p=0.001; MACS and IQ: rs=0.58, p=0.001; CFCS and MACS: rs=0.65,
      p=0.001). The Kruskal-Wallis test was used to determine if there were differences
      between the GMFCS-E&R, the CFCS and the MACS by CP type. CP types showed
      different scores for the IQ level (Chi-square=8.59, df=2, p=0.014), the GMFCS-E&R
      (Chi-square=36.46, df=2, p<0.001), the CFCS (Chi-square=12.87, df=2, p=0.002),
      and the MACS Level (Chi-square=13.96, df=2, p<0.001) but no significant
      differences emerged for the SES (Chi-square=1.19, df=2, p=0.554). This study
      shows how the three functional classifications (GMFCS-E&R, CFCS and MACS)
      complement each other to provide a better description of the functional profile
      of CP. The systematic evaluation of the IQ can provide useful information about a
      possible future outcome for every functional level. The SES does not appear to
      affect functional profiles. 

PMID- 25062095
TI  - Cranberry extract standardized for proanthocyanidins promotes the immune response
      of Caenorhabditis elegans to Vibrio cholerae through the p38 MAPK pathway and HSF
      1.
AB  - Botanicals are rich in bioactive compounds, and some offer numerous beneficial
      effects to animal and human health when consumed. It is well known that
      phytochemicals in cranberries have anti-oxidative and antimicrobial activities.
      Recently, an increasing body of evidence has demonstrated that cranberry
      phytochemicals may have potential benefits that promote healthy aging. Here, we
      use Caenorhabditis elegans as a model to show that water-soluble cranberry
      extract standardized to 4.0% proanthocyanidins (WCESP), a major component of
      cranberries, can enhance host innate immunity to resist against Vibrio cholerae
      (V. cholerae; wild type C6706 (O1 El Tor biotype)) infection. Supplementation of
      WCESP did not significantly alter the intestinal colonization of V. cholerae, but
      upregulated the expression of C. elegans innate immune genes, such as clec-46,
      clec-71, fmo-2, pqn-5 and C23G10.1. Additionally, WCESP treatment did not affect
      the growth of V. cholerae and expression of the major bacterial virulence genes,
      and only slightly reduced bacterial colonization within C. elegans intestine.
      These findings indicate that the major components of WCESP, including
      proanthocyanidins (PACs), may play an important role in enhancing the host innate
      immunity. Moreover, we engaged C. elegans mutants and identified that the p38
      MAPK signaling, insulin/IGF-1 signaling (IIS), and HSF-1 play pivotal roles in
      the WCESP-mediated host immune response. Considering the level of conservation
      between the innate immune pathways of C. elegans and humans, the results of this
      study suggest that WCESP may also play an immunity-promoting role in higher order
      organisms. 

PMID- 25062098
TI  - An RNA Aptamer Targets the PDZ-Binding Motif of the HPV16 E6 Oncoprotein.
AB  - Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus which is the
      primary causative agent of cervical cancer. Cell transformation arises from
      deregulated expression of the E6 and E7 oncogenes. E6 has been shown to bind a
      number of cellular proteins, including p53 and proteins containing a PDZ domain.
      This study reports the first RNA aptamers to E6. These have been employed as
      molecular tools to further investigate E6-p53 and E6-PDZ interactions. This study
      is focussed on two aptamers (termed F2 and F4) which induced apoptosis in cells
      derived from an HPV16-transformed cervical carcinoma. The molecules were able to
      inhibit the interaction between E6 and PDZ1 from Magi1, with F2 being the most
      effective inhibitor. Neither of the aptamers inhibited E6-p53 interaction or p53
      degradation. This study shows the specificity of this approach and highlights the
      potential benefits of the E6 aptamers as potential therapeutic or diagnostic
      agents in the future. 

PMID- 25062097
TI  - Effects of labeling and pointing on object gaze in boys with fragile X syndrome:
      an eye-tracking study.
AB  - We examined the visual processing of a social learning stimulus and the ways in
      which visual attention was distributed to objects as well as to the examiner's
      face during word learning under conditions that varied only in the presence or
      absence of a label. The goal of the current study, then, was to evaluate the
      effects of differentially providing pointing and labeling during exposure to a
      novel target object in males with fragile X syndrome (FXS) (n=14, ages 4.33
      10.02), autism spectrum disorder (ASD) (n=17, ages 4.04-10.4), or typical
      development (TD) (n=18, ages 2.05-5.33). In particular, the present study
      examined attention to the examiner's face as well as target and distracter
      objects that were presented as video stimuli. An eye-tracker captured gaze to the
      video stimuli as they were shown in order to examine the way in which children
      with FXS, ASD, or TD distributed their gaze toward the examiner and the objects.
      Results indicated that no group showed increased gaze toward the target object
      compared to the distracter object. However, results revealed that participants
      with FXS showed significantly increased face gaze compared to the novel objects,
      whereas children with ASD and TD both showed similar amounts of relative gaze
      toward the face and objects. Furthermore, the act of pointing at the target
      object was found to increase gaze toward the target objects compared to when
      there was no pointing in all groups. Together, these findings suggest that social
      cues like those employed in a word-learning task, when presented with video, may
      relate to gaze in FXS in context- or task-dependent ways that are distinct from
      those expected during live interaction. 

PMID- 25062099
TI  - Palladium/copper-catalyzed aerobic intermolecular cyclization of enediyne
      compounds and alkynes: interrupting cycloaromatization for (4 + 2) cross
      benzannulation.
AB  - A tandem coupling-ketooxygenation reaction of readily accessible enediyne
      carboxylic compounds with inner alkynes has been developed that utilizes the
      PdCl2/CuBr2 catalytic system under an O2 atmosphere and assembles a class of
      isoindolinones and o-acylbenzoic acids. The two oxygen atoms are regioselectively
      incorporated into enediyne units at the 1- and 6-positions from atmospheric
      molecular oxygen and H2O, respectively, during the present process. This study
      uncovered a formal [4C + 2C] benzannulation-diketonization of enediynes and
      alkynes via a coupling and decoupling strategy. 

PMID- 25062101
TI  - Comparison of initial experiences of robot-assisted radical cystectomy with those
      of laparoscopic for bladder cancer.
AB  - OBJECTIVE: The aim of the present study was to evaluate perioperative outcomes in
      initial experiences of robot-assisted laparoscopic radical cystectomy (RARC) in
      comparison with those of laparoscopic radical cystectomy (LRC) for muscle
      invasive or high-risk non-muscle-invasive bladder cancer. METHODS: We performed
      RARC on six patients with muscle-invasive or high-risk non-muscle-invasive
      bladder cancer starting in October 2011. During the same period, another five
      patients underwent LRC. Perioperative outcomes in initial experiences of RARC
      were elucidated by comparing them with those of LRC. RESULTS: Robot-assisted
      procedures were completed in all cases without conversion to open surgery. The
      median time of pneumoperitoneum was 252 minutes, and the median blood loss was
      340 mL. No severe complications were observed. Perioperative outcomes did not
      significantly differ between RARC and LRC. Although two cases of troubles in
      uretero-conduit anastomosis sites were observed after LRC, no patients
      experienced postoperative complication related to urinary diversion after RARC.
      CONCLUSIONS: Our data indicate that RARC is an acceptable option even in the
      initial period, and it may become one of the most favorable procedures for
      treatment of muscle-invasive bladder cancer in the near future, although more
      tests and longer follow-ups are required to confirm its effectiveness and safety.

PMID- 25062102
TI  - One-and-a-half ventricular repair for isolated right ventricle metastatic tumor
      resection after lobectomy for lung cancer.
AB  - A 77-year-old woman presented with shortness of breath 1 year after a right upper
      lobectomy for lung cancer. She showed a possible intracardiac metastasis on
      positron emission tomography scan. There was no other evidence of recurrence. The
      large right ventricular mass was associated with the right ventricle free wall,
      the apex, the papillary muscle, and the chordae to the tricuspid valve. After
      mass resection of the right ventricle, a one-and-a-half ventricular repair was
      performed with tricuspid valve replacement and defect closure. The patient was
      discharged on postoperative day 14 without complications and has been well for
      the first 3 months after the surgery. 

PMID- 25062103
TI  - Aortic valve replacement and concomitant right coronary artery bypass grafting
      performed via a right minithoracotomy approach.
AB  - OBJECTIVE: We present our experience of concomitant right coronary artery bypass
      grafting (CABG) and aortic valve replacement performed via a right
      minithoracotomy in patients with coronary lesions not amenable to percutaneous
      intervention. METHODS: A total of 17 patients underwent concomitant aortic valve
      replacement and right CABG between April 2008 and July 2013. A 5- to 6-cm
      minithoracotomy incision was made over the right second or third intercostal
      space, and the costochondral cartilage was transected. A saphenous vein bypass to
      the right coronary artery was then performed, initiating the anastomosis from the
      toe of the graft. Subsequently, the aortic valve was replaced using standard
      techniques. RESULTS: There were 6 men and 11 women. The median European System
      for Cardiac Operative Risk Evaluation II score mortality risk was 5%
      [interquartile range (IQR), 2%-8%]. The mean (SD) age was 77 (10) years, the left
      ventricular ejection fraction was 59% (8%), and the New York Heart Association
      functional class was 2.4 (0.8). One patient had a history of CABG. The mean (SD)
      cardiopulmonary bypass time was 168 (57) minutes, and the aortic cross-clamp time
      was 133 (36) minutes. Three patients underwent concomitant mitral valve surgery
      (replacement, 2; repair, 1). The median intensive care unit and hospital lengths
      of stay were 47 hours (IQR, 24-90) and 9 days (IQR, 5-13), respectively. There
      was one reoperation for bleeding, and there was one postoperative stroke. All
      patients were alive at a mean (SD) follow-up of 2 (1.1) years. CONCLUSIONS:
      Aortic valve replacement with concomitant CABG performed via a right
      minithoracotomy approach is feasible.

PMID- 25062104
TI  - The assessment of arterial stiffness in pre-eclamptic patients; role of
      antihypertensive drugs.

PMID- 25062107
TI  - Fabrication of both the photoactive layer and the electrode by electrochemical
      assembly: towards a fully solution-processable device.
AB  - We present an economical route to achieve an all-solution and vacuum-deposition
      free device for fabrication of both the photoactive layer and the electrode. This
      low cost strategy offers a wide range of possibilities in terms of chemical and
      physical properties for the fabrication of tailor-made materials and their
      devices. 

PMID- 25062106
TI  - Identification of novel GRM1 mutations and single nucleotide polymorphisms in
      prostate cancer cell lines and tissues.
AB  - Metabotropic glutamate receptor 1 (GRM1) signaling has been implicated in benign
      and malignant disorders including prostate cancer (PCa). To further explore the
      role of genetic alterations of GRM1 in PCa, we screened the entire human GRM1
      gene including coding sequence, exon-intron junctions, and flanking untranslated
      regions (UTRs) for the presence of mutations and single nucleotide polymorphisms
      (SNPs) in several PCa cell lines and matched tumor-normal tissues from Caucasian
      Americans (CAs) and African Americans (AAs). We used bidirectional sequencing,
      allele-specific PCR, and bioinformatics to identify the genetic changes in GRM1
      and to predict their functional role. A novel missense mutation identified at
      C1744T (582 Pro > Ser) position of GRM1 gene in a primary AA-PCa cell line
      (E006AA) was predicted to affect the protein stability and functions. Another
      novel mutation identified at exon-intron junction of exon-8 in C4-2B cell line
      resulted in alteration of the GRM1 splicing donor site. In addition, we found
      missense SNP at T2977C (993 Ser > Pro) position and multiple non-coding mutations
      and SNPs in 3'-UTR of GRM1 gene in PCa cell lines and tissues. These novel
      mutations may contribute to the disease by alterations in GRM1 gene splicing,
      receptor activation, and post-receptor downstream signaling. 

PMID- 25062108
TI  - Primary renal neuroblastoma metastasizing into liver and lungs with tumor
      thrombus extension into the right atrium.
AB  - Neuroblastomas are malignant tumors of the sympathetic nervous system. Areas of
      manifestation most commonly involve the abdomen, neck, thorax and pelvis. Primary
      renal neuroblastomas are extremely rare, only a few case reports exist worldwide,
      and even those are discussed controversially.We present the case of a 6-year-old
      girl with a renal tumor and a tumor thrombus extending into the right atrium,
      which radiologically appeared to be a Wilms tumor. Since the lesion did not
      respond to nephroblastoma-specific therapy, a biopsy from one of the liver
      metastases was taken, revealing the revised diagnosis of a clear cell renal cell
      carcinoma. Histopathology of the reference center, however, described a primary
      renal neuroblastoma. After adjusting the chemotherapy tumornephrectomy including
      the complete venous thrombus could be performed without any
      complications.Neuroblastoma originating from a kidney is an absolute rarity that
      can easily be misdiagnosed as Wilms tumor, especially, if a typical tumor
      thrombus with extension into the inferior vena cava is seen. Therefore
      neuronspecific enolase in serum as well as vanillylmandelic acid and homovanillic
      acid in the urine should be determined in all patients when Wilms tumor is
      assumed. To the best of our knowledge, this is the first published case of a
      primary renal neuroblastoma with a tumor thrombus extending into the right
      atrium. 

PMID- 25062109
TI  - Early postnatal diagnosis of Costello syndrome.
AB  - Costello syndrome is a rare congenital disease with typical craniofacial and
      musculoskeletal features, cutaneous lesions, cardiac defects and cancer
      susceptibility. Affected patients show severe feeding difficulties for the first
      years of life and developmental delay. We present the case of a patient, in whom
      fetal tachycardia, polyhdramnios and physical characteristics led to an early
      diagnosis of Costello syndrome. Based on this patient we describe challenges and
      problems of therapeutic management of infants with Costello syndrome. 

PMID- 25062110
TI  - Health related quality of life after corrective surgery for congenital heart
      disease.
AB  - After corrective surgery for congenital heart defects (CHD) many patients suffer
      from residual defects, some with reduced cardiorespiratory capacity and possible
      impairment of their health related quality of life (HRQoL). The aim of our study
      is to evaluate, how children after surgery for CHD rate their HRQoL. METHOD: A
      standardised questionnaire deve-loped for self-rating in children between 8 and
      18 years and dealing with 7 different domains concerning the HRQoL (friends,
      family, physical functioning, cognition, body image, emotional function and
      autonomy) was independently answered from patients and their parents during an
      outpatient visit at their pediatric cardiologist throughout Germany. RESULTS: 173
      patients (40% female, 60% male, mean age 11.6 years) were interviewed, 167
      questionnaires could be evaluated. The mean time interval after surgery was 9.8+/
      3.4 years. Patient had had surgery for complete different types of CHD
      (ventricular septal defects n=50, Tetralogy of Fallot n=51, univentricular heart
      n=26, transposition of great arteries n=40). The results were compared with those
      of an age-matched control group (n=169). Patients with CHD reported a better
      HRQoL than the controls for all items (p<0.01). There was no significant gender
      specific difference. After puberty, the rating for most items, except of "body
      image", had become very similar compared to controls. Pa-rents assessed their
      children significantly worse in 3 domains (friends, body image and emotion;
      p<0.01). CONCLUSION: Children with congenital heart defects are able to develop
      coping structures, that enable them to live a normal life from their individual
      point of view. Integration in psychosocial structures seems to be rather normal
      when compared to healthy controls. Many patients considered their HRQoL as even
      better.

PMID- 25062111
TI  - Neonatal abstinence syndrome in European and North American neonates: differences
      in clinical characteristics derived from a prospective randomized trial.
AB  - BACKGROUND: Due to the steady increase of substance-dependent pregnant women the
      neonatal abstinence syndrome has become an increasingly important issue in
      neonatology. The present study investigates site-specific differences of detailed
      symptoms and treatment of neonatal abstinence syndrome within the context of an
      international multicenter clinical trial. METHODS: Site specific neonatal data
      analyses from a prospective randomized, double-blind, double-dummy clinical trial
      (MOTHER study) was performed. A standardized NAS rating and treatment protocol
      was applied, while non-pharmacological care of NAS symptoms differed across the
      sites. RESULTS: Urban US neonates exhibited most neurological symptoms (p<0.001)
      while in Europe autonomous, respiratory and gastrointestinal symptoms were found
      significantly more often compared to urban and/or rural US (p<0.05). Methadone
      produced significantly greater scores than buprenorphine in neurological,
      behavioural and respiratory symptoms regardless of the sites (ps<0.05). NAS
      treatment rates in all site clusters were similar for methadone-exposed neonates,
      while in Europe significantly more buprenorphine-exposed neonates were treated
      (p=0.001) than in US site clusters. Urban US neonates had significantly higher
      NAS scores (p<0.01) compared to rural US and European neonates, and needed
      significantly higher morphine doses (p<0.05) with longer treatment duration.
      Birth weight, length and head circumference did not differ significantly among
      the site clusters, but APGAR scores were significantly higher in European
      (p<0.01) neonates. CONCLUSION: In addition to intrauterine medication exposure
      other aspects such as different addiction severity of the mothers, different
      treatment modalities including rooming-in as well as the frequency of NAS ratings
      may be influencing the course of NAS.

PMID- 25062112
TI  - Significantly increased CD70 up regulation on TEL-AML positive B cell precursor
      acute lymphoblastic leukemia cells following CD40 stimulation.
AB  - BACKGROUND: TEL-AML the most common genetic alteration in childhood precursor B
      acute lymphoblastic leukemia (BCP-ALL) is associated with a favorable prognosis.
      PATIENTS AND METHOD: We studied the expression of nerve growth factor/tumor
      necrosis factor receptor (NGFR/TNFR)/ligand family members on 108 primary BCP-ALL
      samples by flow cytometry and compared both their baseline expression and CD40
      induced modulation on TEL-AML positive and negative leukemia samples. RESULTS:
      Our findings demonstrate that TEL-AML positive patients exhibit a significantly
      higher percentage of CD40, CD27 and p75NTR positive blasts at diagnosis. This
      might well contribute to the improved relapse-free survival of these patients
      assessed in Kaplan Meier analysis as CD27 and p75NTR directly mediate apoptotic
      signals. Furthermore CD40 ligation enhances antigen presenting and T cell
      stimulatory capacity via significant up regulation of CD70 while adequate
      response to physiological maturation signals as indicated by concomitant down
      regulation of CD27 is retained in TEL-AML positive leukemia. CONCLUSION: These
      data provide novel insights in immunological control mechanisms preserved in this
      leukemia subtype and suggest that not only treatment with chemicals such as HDAC
      inhibitors but also retained in vivo response to CD40 ligation contributes to
      improved immune surveillance in these patients which may add to a superior
      relapse-free survival observed particularly in the presence of other risk
      factors.

PMID- 25062113
TI  - Neurofibromatosis type 1 (NF1) and associated tumors.
AB  - Neurofibromatosis type 1 (NF1) is a frequent neurocutaneous syndrome that
      predisposes for various benign and malignant tumors. Most characteristic are
      neurofibromas which occur in almost all NF1 patients at some point in lifetime.
      Although neurofibromas are benign tumors they can be disfiguring and plexiform
      neurofibromas may progress to malignant peripheral nerve sheath tumors. Overall
      survival rates of patients with these malignant tumors are poor. Other neoplasias
      frequently observed in NF1 patients are pilocytic astrocytomas, gastrointestinal
      stromal tumors, pheochromocytomas and juvenile myelomonocytic leukemia. Several
      other tumors have been reported in NF1 patients but it is unclear if there is a
      true association between the particular tumor type and NF1. Some of these tumors
      might be caused by a rare recessively inherited childhood cancer syndrome termed
      constitutive mismatch repair deficiency syndrome which shows certain phenotypic
      overlap with NF1 but includes a broad spectrum of tumors which usually do not
      occur in NF1. The development of NF1-associated tumors is largely explained by
      the underlying defect of the NF1 gene which results in activation of the RAS
      proto-oncogene- a key mechanism of tumorigenesis. Several downstream effectors of
      activated RAS as well as cooperating molecular pathways have been identified.
      These insights provide the basis to develop novel targeted treatment strategies
      which are urgently needed to improve the outcome for patients with NF1-associated
      malignancies. 

PMID- 25062114
TI  - Cancer Risk Awareness and Concern among Women with a Family History of Breast or
      Ovarian Cancer.
AB  - Women with a documented deleterious mutation in BRCA1 or BRCA2 are at
      substantially elevated risk for ovarian cancer. To understand what percentage of
      women with high-risk family histories know their risk is elevated we surveyed
      1,885 women with a high- or moderate-risk family history and no personal history
      of breast or ovarian cancer, and asked about their perceived risk of breast and
      ovarian cancer. Among high-risk women, fewer than 20% reported use of genetic
      counseling, and knowledge of elevated risk of ovarian cancer was low. Prior
      genetic counseling was associated with greater perceived risk for ovarian cancer.
      Results suggest that most high-risk women (>75%) do not know their risk for
      ovarian cancer. Identification of potentially high-risk women for referral to
      genetic counseling may improve informed ovarian cancer risk management. 

PMID- 25062115
TI  - Decline in Japanese encephalitis, Kushinagar District, Uttar Pradesh, India.

PMID- 25062116
TI  - Rain-induced increase in background radiation detected by Radiation Portal
      Monitors.
AB  - A complete understanding of both the steady state and transient background
      measured by Radiation Portal Monitors (RPMs) is essential to predictable system
      performance, as well as maximization of detection sensitivity. To facilitate this
      understanding, a test bed for the study of natural background in RPMs has been
      established at the Oak Ridge National Laboratory. This work was performed in
      support of the Second Line of Defense Program's mission to enhance partner
      country capability to deter, detect, and interdict the illicit movement of
      special nuclear material. In the present work, transient increases in gamma-ray
      counting rates in RPMs due to rain are investigated. The increase in background
      activity associated with rain, which has been well documented in the field of
      environmental radioactivity, originates primarily from the wet-deposition of two
      radioactive daughters of (222)Rn, namely, (214)Pb and (214)Bi. In this study,
      rainfall rates recorded by a co-located weather station are compared with RPM
      count rates and high-purity germanium spectra. The data verify that these
      radionuclides are responsible for the largest environmental background
      fluctuations in RPMs. Analytical expressions for the detector response function
      in Poly-Vinyl Toluene have been derived. Effects on system performance and
      potential mitigation strategies are discussed. 

PMID- 25062117
TI  - Ribosomal protein S19-binding domain provides insights into hantavirus
      nucleocapsid protein-mediated translation initiation mechanism.
AB  - The hantaviral zoonotic diseases pose a significant threat to human health due to
      the lack of potential antiviral therapeutics or a vaccine against hantaviruses. N
      (Sin Nombre hantavirus nucleocapsid protein) augments mRNA translation. N binds
      to both the mRNA 5' cap and 40S ribosomal subunit via RPS19 (ribosomal protein
      S19). N with the assistance of the viral mRNA 5'-UTR preferentially favours the
      translation of a downstream ORF. We identified and characterized the RPS19
      binding domain at the N-terminus of N. Its deletion did not influence the
      secondary structure, but affected the conformation of trimeric N molecules. The N
      variant lacking the RPS19-binding region was able to bind both the mRNA 5' cap
      and panhandle-like structure, formed by the termini of viral genomic RNA. In
      addition, the N variant formed stable trimers similar to wild-type N. Use of this
      variant in multiple experiments provided insights into the mechanism of ribosome
      loading during N-mediated translation strategy. The present study suggests that N
      molecules individually associated with the mRNA 5' cap and RPS19 of the 40S
      ribosomal subunit undergo N-N interaction to facilitate the engagement of N
      associated ribosomes at the mRNA 5' cap. This has revealed new targets for
      therapeutic intervention of hantavirus infection. 

PMID- 25062118
TI  - Expression of Ki-67, Oct-4, gamma-tubulin and alpha-tubulin in human tooth
      development.
AB  - AIMS: To analyze factors controlling cell proliferation and differentiation, and
      appearance of primary cilia during the cap and bell stages of incisor or/and
      canine human enamel organs. MATERIALS AND METHODS: Qualitative and quantitative
      analysis of proliferating Ki-67 positive cells and expression of gamma-tubulin,
      alpha-tubulin and Oct-4 was immunohistochemically analyzed in the cap an bell
      stages of 10 developing human incisor and canine germs, 8-21 weeks old. RESULTS:
      During the analyzed period, ratio of Ki-67 positive cells changed in outer enamel
      epithelium from 48.86% to 24.52%, in inner enamel epithelium increased from
      56.11% to 60.06% and then dropped to 44.24%. While in dental papilla
      proliferation first increased from 46.26% to 55.45%, and then dropped to 22.08%,
      a constant decrease of proliferation characterized enamel reticulum (from 46.26%
      to 15.49%). Strong cytoplasmic Oct-4 expression characterized epithelial parts of
      enamel organ, particularly the differentiating ameloblasts. During further
      development, Oct-4 expression shifted to both nuclear and cytoplasmic expression
      in mesenchymal tooth components. Primary cilia characterized most of the cells in
      developing enamel organ. While non-ciliated (proliferating) cells mainly
      contained two centrioles (gamma-tubulin), the primary cilia (alpha-tubulin) were
      arising from basal bodies (gamma-tubulin) of non-proliferating cells.
      CONCLUSIONS: We suggest that increase in cell proliferation enables growth of
      enamel organ, while its selective decrease leads to disintegration of some tooth
      parts. Drop of proliferation coincided with initiation of ameloblast and
      odontoblast differentiation. Additionally, cell differentiation was accompanied
      by increased expression of Oct-4 and probably by signalling via primary cilia,
      both regulating processes of cell proliferation and differentiation.

PMID- 25062119
TI  - Testing the implicit processing hypothesis of precognitive dream experience.
AB  - Seemingly precognitive (prophetic) dreams may be a result of one's unconscious
      processing of environmental cues and having an implicit inference based on these
      cues manifest itself in one's dreams. We present two studies exploring this
      implicit processing hypothesis of precognitive dream experience. Study 1
      investigated the relationship between implicit learning, transliminality, and
      precognitive dream belief and experience. Participants completed the Serial
      Reaction Time task and several questionnaires. We predicted a positive
      relationship between the variables. With the exception of relationships between
      transliminality and precognitive dream belief and experience, this prediction was
      not supported. Study 2 tested the hypothesis that differences in the ability to
      notice subtle cues explicitly might account for precognitive dream beliefs and
      experiences. Participants completed a modified version of the flicker paradigm.
      We predicted a negative relationship between the ability to explicitly detect
      changes and precognitive dream variables. This relationship was not found. There
      was also no relationship between precognitive dream belief and experience and
      implicit change detection. 

PMID- 25062121
TI  - Dye-sensitized MoS2 photodetector with enhanced spectral photoresponse.
AB  - We fabricated dye-sensitized MoS2 photodetectors that utilized a single-layer
      MoS2 treated with rhodamine 6G (R6G) organic dye molecules (with an optical band
      gap of 2.38 eV or 521 nm). The proposed photodetector showed an enhanced
      performance with a broad spectral photoresponse and a high photoresponsivity
      compared with the properties of the pristine MoS2 photodetectors. The R6G dye
      molecules deposited onto the MoS2 layer increased the photocurrent by an order of
      magnitude due to charge transfer of the photoexcited electrons from the R6G
      molecules to the MoS2 layer. Importantly, the photodetection response extended to
      the infrared (lambda < 980 nm, which corresponded to about half the energy band
      gap of MoS2), thereby distinguishing the device performance from that of a
      pristine MoS2 device, in which detection was only possible at wavelengths shorter
      than the band gap of MoS2, i.e., lambda < 681 nm. The resulting device exhibited
      a maximum photoresponsivity of 1.17 AW(-1), a photodetectivity of 1.5 * 10(7)
      Jones, and a total effective quantum efficiency (EQE) of 280% at 520 nm. The
      device design described here presents a significant step toward high-performance
      2D nanomaterial-based photodetector.

PMID- 25062120
TI  - Dispositional mindfulness is associated with reduced implicit learning.
AB  - Behavioral and neuroimaging evidence suggest that mindfulness exerts its salutary
      effects by disengaging habitual processes supported by subcortical regions and
      increasing effortful control processes supported by the frontal lobes. Here we
      investigated whether individual differences in dispositional mindfulness relate
      to performance on implicit sequence learning tasks in which optimal learning may
      in fact be impeded by the engagement of effortful control processes. We report
      results from two studies where participants completed a widely used questionnaire
      assessing mindfulness and one of two implicit sequence learning tasks. Learning
      was quantified using two commonly used measures of sequence learning. In both
      studies we detected a negative relationship between mindfulness and sequence
      learning, and the relationship was consistent across both learning measures. Our
      results, the first to show a negative relationship between mindfulness and
      implicit sequence learning, suggest that the beneficial effects of mindfulness do
      not extend to all cognitive functions. 

PMID- 25062122
TI  - Modulation of immune responses by immunotherapy in allergic diseases.
AB  - Allergen immunotherapy (AIT) has been used for 100 years and until now different
      immunoregulatory pathways have been shown to take place in its mechanisms of
      action. It is characterized by administration of the causative allergen and is
      shown to be clinically efficient even after discontinuation of therapy
      particularly in allergic respiratory diseases, bee venom allergy, and food
      allergy. Generation of antigen/allergen-specific peripheral tolerance is the key
      mechanism during immunotherapy. It is mediated by development of T and B
      regulatory cells, IgG4 isotype allergen-specific antibodies and the involvement
      of multiple suppressor factors, which lead to decreased tissue inflammation,
      early and late phase responses. Describing novel regulatory mechanisms in the
      process of immune tolerance induction will help to identify treatment modalities
      not only for allergic disorders, but also for autoimmune diseases, organ
      transplantation, chronic infections, and cancer. 

PMID- 25062123
TI  - Pharmacological modulation of monocytes and macrophages.
AB  - Mononuclear phagocytes are major players in diverse pathological conditions which
      include chronic inflammatory diseases, infection, autoimmunity, atherosclerosis,
      metabolic disorders, and cancer. Plasticity is a fundamental property of cells of
      the monocyte-macrophage lineage and a variety of modulators profoundly affect
      monocytes and macrophages. Tumor-associated macrophages (TAMs) provide a paradigm
      for macrophage plasticity and anticancer therapeutic modalities (chemotherapy,
      radiotherapy, and immunotherapy) profoundly affect their function. The
      development of innovative strategies targeting cells of the monocyte-macrophage
      lineage may pave the way to innovative therapies for a wide range of diseases. 

PMID- 25062124
TI  - Connecting bulk viscosity measurements to kinetic limitations on attaining
      equilibrium for a model aerosol composition.
AB  - The growth, composition, and evolution of secondary organic aerosol (SOA) are
      governed by properties of individual compounds and ensemble mixtures that affect
      partitioning between the vapor and condensed phase. There has been considerable
      recent interest in the idea that SOA can form highly viscous particles where the
      diffusion of either water or semivolatile organics within the particle is
      sufficiently hindered to affect evaporation and growth. Despite numerous indirect
      inferences of viscous behavior from SOA evaporation or "bounce" within aerosol
      instruments, there have been no bulk measurements of the viscosity of well
      constrained model aerosol systems of atmospheric significance. Here the viscous
      behavior of a well-defined model system of 9 dicarboxylic acids is investigated
      directly with complementary measurements and model predictions used to infer
      phase state. Results not only allow us to discuss the atmospheric implications
      for SOA formation through this representative mixture, but also the potential
      impact of current methodologies used for probing this affect in both the
      laboratory and from a modeling perspective. We show, quantitatively, that the
      physical state transformation from liquid-like to amorphous semisolid can
      substantially increase the importance of mass transfer limitations within
      particles by 7 orders of magnitude for 100 nm diameter particles. Recommendations
      for future research directions are given. 

PMID- 25062125
TI  - Chikungunya in the Caribbean--threat for Europe.

PMID- 25062126
TI  - Quantifying separation and similarity in a Saccharomyces cerevisiae
      metapopulation.
AB  - Eukaryotic microbes are key ecosystem drivers; however, we have little theory and
      few data elucidating the processes influencing their observed population
      patterns. Here we provide an in-depth quantitative analysis of population
      separation and similarity in the yeast Saccharomyces cerevisiae with the aim of
      providing a more detailed account of the population processes occurring in
      microbes. Over 10,000 individual isolates were collected from native plants,
      vineyards and spontaneous ferments of fruit from six major regions spanning 1000
      km across New Zealand. From these, hundreds of S. cerevisiae genotypes were
      obtained, and using a suite of analytical methods we provide comprehensive
      quantitative estimates for both population structure and rates of gene flow or
      migration. No genetic differentiation was detected within geographic regions,
      even between populations inhabiting native forests and vineyards. We do, however,
      reveal a picture of national population structure at scales above ~100 km with
      distinctive populations in the more remote Nelson and Central Otago regions
      primarily contributing to this. In addition, differential degrees of connectivity
      between regional populations are observed and correlate with the movement of
      fruit by the New Zealand wine industry. This suggests some anthropogenic
      influence on these observed population patterns.

PMID- 25062127
TI  - Microbial degradation of isosaccharinic acid at high pH.
AB  - Intermediate-level radioactive waste (ILW), which dominates the radioactive waste
      inventory in the United Kingdom on a volumetric basis, is proposed to be disposed
      of via a multibarrier deep geological disposal facility (GDF). ILW is a
      heterogeneous wasteform that contains substantial amounts of cellulosic material
      encased in concrete. Upon resaturation of the facility with groundwater, alkali
      conditions will dominate and will lead to the chemical degradation of cellulose,
      producing a substantial amount of organic co-contaminants, particularly
      isosaccharinic acid (ISA). ISA can form soluble complexes with radionuclides,
      thereby mobilising them and posing a potential threat to the surrounding
      environment or 'far field'. Alkaliphilic microorganisms sampled from a legacy
      lime working site, which is an analogue for an ILW-GDF, were able to degrade ISA
      and couple this degradation to the reduction of electron acceptors that will
      dominate as the GDF progresses from an aerobic 'open phase' through nitrate- and
      Fe(III)-reducing conditions post closure. Furthermore, pyrosequencing analyses
      showed that bacterial diversity declined as the reduction potential of the
      electron acceptor decreased and that more specialised organisms dominated under
      anaerobic conditions. These results imply that the microbial attenuation of ISA
      and comparable organic complexants, initially present or formed in situ, may play
      a role in reducing the mobility of radionuclides from an ILW-GDF, facilitating
      the reduction of undue pessimism in the long-term performance assessment of such
      facilities. 

PMID- 25062128
TI  - Discovery of clinical candidate 1-(4-(3-(4-(1H-benzo[d]imidazole-2
      carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone (AMG 579), a potent,
      selective, and efficacious inhibitor of phosphodiesterase 10A (PDE10A).
AB  - We report the identification of a PDE10A clinical candidate by optimizing potency
      and in vivo efficacy of promising keto-benzimidazole leads 1 and 2. Significant
      increase in biochemical potency was observed when the saturated rings on
      morpholine 1 and N-acetyl piperazine 2 were changed by a single atom to
      tetrahydropyran 3 and N-acetyl piperidine 5. A second single atom modification
      from pyrazines 3 and 5 to pyridines 4 and 6 improved the inhibitory activity of 4
      but not 6. In the in vivo LC-MS/MS target occupancy (TO) study at 10 mg/kg, 3, 5,
      and 6 achieved 86-91% occupancy of PDE10A in the brain. Furthermore, both CNS TO
      and efficacy in PCP-LMA behavioral model were observed in a dose dependent
      manner. With superior in vivo TO, in vivo efficacy and in vivo PK profiles in
      multiple preclinical species, compound 5 (AMG 579) was advanced as our PDE10A
      clinical candidate. 

PMID- 25062129
TI  - Contact lens lipid spoliation of hydrogel and silicone hydrogel lenses.
AB  - PURPOSE: The purpose of the study was to measure contact lens lipid spoliation of
      silicone hydrogel PureVision (balafilcon A) and hydrogel Acuvue 2 (etafilcon A)
      contact lenses worn for 10 hours single use (DD) and 7 days of extended wear
      (EW). METHODS: Two similar study populations (DD, n = 55; EW, n = 53), were
      enrolled at four study sites. In each population, a bilateral, randomized,
      crossover (lens material), subject-masked experimental design was followed. Worn
      contact lenses were analyzed for lipid uptake using high-performance liquid
      chromatography by two laboratories: Alcon Laboratories (right lens total uptake)
      and OTG Research & Consultancy (left lens total uptake and individual lipid
      classes). RESULTS: Lipid uptake was different for the two materials: total lipid
      (p < 0.007), cholesterol esters (p < 0.001), cholesterol (p < 0.001 EW only), and
      triglycerides/phospholipids (p < 0.001) were higher for balafilcon A, whereas
      fatty acid (p < 0.0025 EW only) was higher for etafilcon A. The ratio of the
      extracted lipids was also different: higher percentages of
      triglycerides/phospholipids (p < 0.001) and cholesterol (p < 0.001 EW only) for
      balafilcon A and higher percentages of fatty acids/di- and monoglycerides (p <
      0.014) for etafilcon A. CONCLUSIONS: Total lipid uptake was highly material
      dependent. Both laboratories measured a greater uptake of lipids by the silicone
      hydrogel than the hydrogel material, a difference that was evident after only 10
      hours of DD. Total lipid uptake was greater after 7 days of EW compared with 10
      hours of DD. Of interest for contact lens spoliation and its avoidance was the
      differential lipid uptake profile, indicating material selectivity. Whereas
      greater differentiation between materials was possible after 7 days of EW for
      each material, the lipid uptake profile was similar for DD and EW, indicating a
      greater material effect than a wear modality effect.

PMID- 25062130
TI  - Learning to read vertical text in peripheral vision.
AB  - PURPOSE: English-language text is almost always written horizontally. Text can be
      formatted to run vertically, but this is seldom used. Several studies have found
      that horizontal text can be read faster than vertical text in the central visual
      field. No studies have investigated the peripheral visual field. Studies have
      also concluded that training can improve reading speed in the peripheral visual
      field for horizontal text. We aimed to establish whether the horizontal vertical
      differences are maintained and if training can improve vertical reading in the
      peripheral visual field. METHODS: Eight normally sighted young adults
      participated in the first study. Rapid serial visual presentation (RSVP) reading
      speed was measured for horizontal and vertical text in the central visual field
      and at 10 degrees eccentricity in the upper or lower (horizontal text) and right
      or left (vertical text) visual fields. Twenty-one normally sighted young adults
      split equally between two training groups and one control group participated in
      the second study. Training consisted of RSVP reading using either vertical text
      in the left visual field or horizontal text in the inferior visual field.
      Subjects trained daily over 4 days. Pre- and post- horizontal and vertical RSVP
      reading speeds were carried out for all groups. For the training groups, these
      measurements were repeated 1 week and 1 month posttraining. RESULTS: Before
      training, RSVP reading speeds were faster for horizontal text in the central and
      peripheral visual fields when compared with vertical text. Training vertical
      reading improved vertical reading speeds by an average factor of 2.8. There was
      partial transfer of training to the opposite (right) hemifield. The training
      effects were retained for up to a month. CONCLUSIONS: Rapid serial visual
      presentation training can improve RSVP vertical text reading in peripheral
      vision. These findings may have implications for patients with macular
      degeneration or hemianopic field loss.

PMID- 25062131
TI  - Alcohol-assisted debridement in PRK with intraoperative mitomycin C.
AB  - PURPOSE: To compare corneal stromal and endothelial cells after photorefractive
      keratectomy with intraoperative mitomycin C in alcohol-assisted versus mechanical
      epithelial debridement using confocal microscopy. METHODS: This prospective
      randomized comparative study was performed on 88 eyes (44 patients) with myopia
      up to -6.00 diopters. The right eye of each patient was randomly assigned to
      either mechanical or alcohol-assisted groups, and the left eye was assigned to
      the alternate group. Confocal microscopy was performed preoperatively and at 3
      months postoperatively. The main outcome measures were epithelial thickness;
      number of keratocytes in the anterior, mid-, and posterior stroma; and
      characteristics of the central corneal endothelial cells in terms of density,
      mean cell area, and polymegathism and hexagonality. RESULTS: Three months after
      surgery, no statistically significant difference was noted between the study
      groups in terms of epithelial thickness. We also found no statistically
      significant difference in central corneal endothelial cells regarding cell
      density, mean cell area, hexagonality, or polymegathism. Compared with baseline
      values, the density of mid- and posterior stromal keratocytes showed no
      significant change in either group, whereas it decreased significantly in the
      anterior stroma in both groups 3 months after surgery. CONCLUSIONS: We found that
      the adverse effects of photorefractive keratectomy with mitomycin C on central
      corneal endothelial cells were comparable between the mechanical and alcohol
      assisted epithelial debridement groups and the significant decrease in
      postoperative keratocyte density in anterior stroma was comparable between the
      two groups. The choice of their application could be left to the discretion of
      the ophthalmologist.

PMID- 25062132
TI  - The relationship between tear meniscus regularity and conjunctival folds.
AB  - PURPOSE: To investigate the capability of a new portable digital meniscometer
      (PDM) to measure tear meniscus radius (TMR) and tear meniscus height (TMH) at
      different locations along the lower lid and to evaluate relationships between
      tear meniscus regularity and the degree of lid-parallel conjunctival folds
      (LIPCOFs). METHODS: Using the PDM, the TMR and TMH of 42 subjects were measured
      at three locations along the lower lid of one eye: central, perpendicularly below
      the pupil center (TMR-C, TMH-C), and temporal (TMR-T, TMH-T) and nasal (TMR-N,
      TMH-N), perpendicularly below the limbus. Nasal and temporal LIPCOF grades were
      recorded. Correlations between the measurements were analyzed using the Pearson
      coefficient (or Spearman rank in nonparametric data), and the differences were
      evaluated by paired t tests or analysis of variance and post hoc Fisher least
      significant difference test. RESULTS: Temporal TMR was 0.041 mm flatter (p =
      0.002) and TMH-T was 0.063 mm higher (p < 0.001), whereas TMR-N was 0.026 mm
      flatter (p = 0.038) and TMH-N was 0.046 mm higher (p < 0.001) than TMR-C and TMH
      C. Temporal LIPCOF grades were significantly correlated to temporal alterations
      in TMH (r = 0.590; p < 0.001) and TMR (r = 0.530; p < 0.001), and nasal LIPCOF
      grades were significantly correlated to nasal alterations in TMH (r = 0.492; p =
      0.001) and TMR (r = 0.350; p = 0.023). CONCLUSIONS: The PDM is able to
      noninvasively detect significant differences in TMR and TMH along the lower lid.
      The flatter TMR and higher TMH at the nasal and temporal locations are associated
      with increased LIPCOF. Because increased LIPCOF scores may affect tear film
      disruption along the lower lid, measuring TMR and TMH at the central position
      below the pupil may provide the best intersubject reliability.

PMID- 25062133
TI  - Central and peripheral autorefraction repeatability in normal eyes.
AB  - PURPOSE: To determine the between-visit repeatability of peripheral
      autorefraction measurements using the Grand Seiko WAM-5500 in normal eyes.
      METHODS: Cycloplegic autorefraction of the right eye was measured on 25 myopic
      young adults using a modified Grand Seiko autorefractor. Measurements were made
      centrally (along the line of sight) and +/-20, +/-30, and +/-40 degrees from the
      line of sight in the horizontal meridian at two visits separated by 1 to 15 days.
      Five autorefraction measurements at each location were converted to vector space
      and averaged. Relative peripheral refraction (RPR) was calculated as the
      difference between the peripheral and central spherical equivalent. Between-visit
      repeatability was evaluated by plotting the difference versus the mean of the
      measurements at the two visits (bias) and by calculating the 95% limits of
      agreement (LoA). RESULTS: The mean (+/-SD) age and spherical-equivalent
      refractive error centrally (at visit 1) were 24.0 +/- 1.3 years and -3.45 +/-
      1.42 diopters (D), respectively. There was no significant between-visit bias for
      any refractive component evaluated (M, J0, J45, and RPR) at any location measured
      (all p > 0.05). The 95% LoA of defocus (M) was +/-0.21 D centrally and increased
      with increasing eccentricity to +/-0.73 and +/-0.88 D at 40 degrees nasally and
      temporally on the retina, respectively. The 95% LoA of RPR increased with
      increasing eccentricity to +/-0.67 and +/-0.82 D at 40 degrees nasally and
      temporally on the retina, respectively. CONCLUSIONS: In normal eyes, the
      repeatability of cycloplegic autorefraction was best centrally and decreased as
      eccentricity increased; however, repeatability in the far periphery was still
      better than previously reported between-visit repeatability for foveal
      cycloplegic subjective refraction. With clear knowledge of the repeatability of
      on- and off-axis cycloplegic autorefraction with the Grand Seiko, peripheral
      measurements can be properly interpreted in longitudinal studies.

PMID- 25062135
TI  - What's your diagnosis? Infantile glaucoma. . .and discoid cataracts.
      Oculocerebrorenal syndrome of Lowe.

PMID- 25062134
TI  - Surgical management of a case of divergence insufficiency in a pseudophakic adult
      patient.

PMID- 25062136
TI  - Bonds that belong in the Hall of fame.

PMID- 25062137
TI  - OCT infrared reflectance imaging in the diagnosis of neurofibromatosis type 1.

PMID- 25062138
TI  - Pediatric canalicular lacerations: epidemiology and variables affecting repair
      success.
AB  - PURPOSE: To evaluate the epidemiology and outcomes of all pediatric canalicular
      lacerations at a high-volume urban tertiary eye care center. Variables of repair
      were evaluated in relation to age and success of repair. METHODS: A retrospective
      review over a 10-year span of all primary pediatric canalicular laceration
      repairs was performed. Variables included patient demographics, repair setting,
      mechanism of injury, associated injuries, type of stent used, and success of
      repair. RESULTS: Of 137 canalicular lacerations evaluated, 27.7% occurred in
      patients younger than 18 years. The majority of the children were male (73.7%)
      and white (68.4%), with a mean age of 10.8 years (range: 1.1 to 17.9 years). The
      mechanism of injury was significantly more likely to be due to dog bites in
      children when compared to adults (P < .0001), particularly those younger than 10
      years (P = .0068). Repair was significantly more successful in the operating room
      than the minor procedure room, regardless of type of stent used (P = .0247). The
      majority of children did not have other injuries (60.5%). However, of the other
      injuries sustained, 52.6% required further monitoring or repair. CONCLUSIONS:
      Pediatric canalicular lacerations are most common in young boys and dog bites are
      the most common etiology. Although many children may not have other injuries,
      full examination is warranted because other injuries may require intervention or
      more frequent monitoring.

PMID- 25062139
TI  - WEBINO after binge drinking.

PMID- 25062140
TI  - Effect of a long alkyl group on cyclopentadithiophene as a conjugated bridge for
      D-A-pi-A organic sensitizers: IPCE, electron diffusion length, and charge
      recombination.
AB  - The option of using conjugated pi-linkers is critical for rational molecular
      design toward an energy-level strategy for organic sensitizers. To further
      optimize photovoltaic performance, methyl- and octyl-substituted 4H
      cyclopenta[2,1-b:3,4-b']dithiophene (CPDT) are introduced into D-A-pi-A featured
      sensitizers. Along with CPDT, instead of thiophene as conjugated bridge, WS-39
      and WS-43 exhibit an extended spectral response due to the excellent conjugation
      and coplanarity of CPDT. Specifically, we focused on the critical effect of
      length of the alkyl group linked to the bridging carbon atoms of CPDT on the
      photovoltaic performances. Octyl-substituted WS-39 shows a broader IPCE onset
      with an enhanced photovoltage relative to the analogue WS-5. In contrast, WS-43,
      with methyl substituted on the CPDT moiety, presents a relatively low quantum
      conversion efficiency within the whole spectral response region, along with low
      photocurrent density. WS-43 displays a distinctly low IPCE platform,
      predominately arising from the short electron diffusion length with significant
      electron loss during the electron transport. The relative movement of the
      conduction band edge (E(CB)) and charge transfer resistance as well as lifetime
      of injected electrons are studied in detail. Under standard AM 1.5 conditions, WS
      39-based solar cells show a promising photovoltaic efficiency of 9.07% (J(SC) =
      16.61 mA cm(-2), V(OC) = 770 mV, FF = 0.71). The octyl chains attached on CPDT
      can provide dual protection and exhibit a high propensity to prevent binding of
      the iodide-triiodide redox couple, producing an efficient shielding effect to
      retard the charge recombination and resulting in improvement of V(OC). Our
      research paves the way to explore more efficient sensitizers through ingenious
      molecular engineering.

PMID- 25062141
TI  - A Black woman's commentary on breastfeeding.

PMID- 25062142
TI  - Spectral and entanglement properties of the bosonic Haldane insulator.
AB  - We discuss the existence of a nontrivial topological phase in one-dimensional
      interacting systems described by the extended Bose-Hubbard model with a mean
      filling of one boson per site. Performing large-scale density-matrix
      renormalization group calculations we show that the presence of nearest-neighbor
      repulsion enriches the ground-state phase diagram of the paradigmatic Bose
      Hubbard model by stabilizing a novel gapped insulating state, the so-called
      Haldane insulator, which, embedded into superfluid, Mott insulator, and density
      wave phases, is protected by the lattice inversion symmetry. The quantum phase
      transitions between the different insulating phases were determined from the
      central charge via the von Neumann entropy. The Haldane phase reveals a
      characteristic fourfold degeneracy of the entanglement spectrum. We finally
      demonstrate that the intensity maximum of the dynamical charge structure factor,
      accessible by Bragg spectroscopy, features the gapped dispersion known from the
      spin-1 Heisenberg chain. 

PMID- 25062143
TI  - Quantum steering ellipsoids.
AB  - The quantum steering ellipsoid of a two-qubit state is the set of Bloch vectors
      that Bob can collapse Alice's qubit to, considering all possible measurements on
      his qubit. We provide an elementary construction of the ellipsoid for arbitrary
      states, calculate its volume, and explain how this geometric representation can
      be made faithful. The representation provides a range of new results, and
      uncovers new features, such as the existence of "incomplete steering" in
      separable states. We show that entanglement can be analyzed in terms of three
      geometric features of the ellipsoid and prove that a state is separable if and
      only if it obeys a "nested tetrahedron" condition. 

PMID- 25062144
TI  - Thermal and nonthermal signatures of the Unruh effect in Casimir-Polder forces.
AB  - We show that Casimir-Polder forces between two relativistic uniformly accelerated
      atoms exhibit a transition from the short distance thermal-like behavior
      predicted by the Unruh effect to a long distance nonthermal behavior, associated
      with the breakdown of a local inertial description of the system. This
      phenomenology extends the Unruh thermal response detected by a single accelerated
      observer to an accelerated spatially extended system of two particles, and we
      identify the characteristic length scale for this crossover with the inverse of
      the proper acceleration of the two atoms. Our results are derived separating at
      fourth order in perturbation theory the contributions of vacuum fluctuations and
      radiation reaction field to the Casimir-Polder interaction between two atoms
      moving in two generic stationary trajectories separated by a constant distance
      and linearly coupled to a scalar field. The field can be assumed in its vacuum
      state or at finite temperature, resulting in a general method for the computation
      of Casimir-Polder forces in stationary regimes. 

PMID- 25062145
TI  - Determination of scale-invariant equations of state without fitting parameters:
      application to the two-dimensional Bose gas across the Berezinskii-Kosterlitz
      Thouless transition.
AB  - We present a general "fit-free" method for measuring the equation of state (EoS)
      of a scale-invariant gas. This method, which is inspired from the procedure
      introduced by Ku et al. [Science 335, 563 (2012)] for the unitary three
      dimensional Fermi gas, provides a general formalism which can be readily applied
      to any quantum gas in a known trapping potential, in the frame of the local
      density approximation. We implement this method on a weakly interacting two
      dimensional Bose gas across the Berezinskii-Kosterlitz-Thouless transition and
      determine its EoS with unprecedented accuracy in the critical region. Our
      measurements provide an important experimental benchmark for classical-field
      approaches which are believed to accurately describe quantum systems in the
      weakly interacting but nonperturbative regime.

PMID- 25062146
TI  - Optomechanical sensing of spontaneous wave-function collapse.
AB  - Quantum experiments with nanomechanical oscillators are regarded as a test bed
      for hypothetical modifications of the Schrodinger equation, which predict a
      breakdown of the superposition principle and induce classical behavior at the
      macroscale. It is generally believed that the sensitivity to these unconventional
      effects grows with the mass of the mechanical quantum system. Here we show that
      the opposite is the case for optomechanical systems in the presence of generic
      noise sources, such as thermal and measurement noise. We determine conditions for
      distinguishing these decoherence processes from possible collapse-induced
      decoherence in continuous optomechanical force measurements. 

PMID- 25062147
TI  - Anomalous minimum in the shear viscosity of a Fermi gas.
AB  - We measure the static shear viscosity eta in a two-component Fermi gas near a
      broad collisional (Feshbach) resonance, as a function of interaction strength and
      energy. We find that eta has both a quadratic and a linear dependence on the
      interaction strength 1/(k(FI)a), where a is the s-wave scattering length and
      k(FI) is the Fermi wave vector for an ideal gas at the trap center. For energies
      above the superfluid transition, the minimum in eta as a function of interaction
      strength is significantly shifted toward the BEC side of resonance, to
      1/(k(FI)a)?0.25.

PMID- 25062148
TI  - Ignorance is bliss: general and robust cancellation of decoherence via no
      knowledge quantum feedback.
AB  - A "no-knowledge" measurement of an open quantum system yields no information
      about any system observable; it only returns noise input from the environment.
      Surprisingly, performing such a no-knowledge measurement can be advantageous. We
      prove that a system undergoing no-knowledge monitoring has reversible noise,
      which can be canceled by directly feeding back the measurement signal. We show
      how no-knowledge feedback control can be used to cancel decoherence in an
      arbitrary quantum system coupled to a Markovian reservoir that is being
      monitored. Since no-knowledge feedback does not depend on the system state or
      Hamiltonian, such decoherence cancellation is guaranteed to be general and
      robust, and can operate in conjunction with any other quantum control protocol.
      As an application, we show that no-knowledge feedback could be used to improve
      the performance of dissipative quantum computers subjected to local loss. 

PMID- 25062149
TI  - Realization of the Dicke model using cavity-assisted Raman transitions.
AB  - We realize an open version of the Dicke model by coupling two hyperfine ground
      states using two cavity-assisted Raman transitions. The interaction due to only
      one of the couplings is described by the Tavis-Cummings model and we observe a
      normal mode splitting in the transmission around the dispersively shifted cavity.
      With both couplings present the dynamics are described by the Dicke model and we
      measure the onset of superradiant scattering into the cavity above a critical
      coupling strength. 

PMID- 25062150
TI  - How psi-epistemic models fail at explaining the indistinguishability of quantum
      states.
AB  - We study the extent to which psi-epistemic models for quantum measurement
      statistics-models where the quantum state does not have a real, ontic status-can
      explain the indistinguishability of nonorthogonal quantum states. This is done by
      comparing the overlap of any two quantum states with the overlap of the
      corresponding classical probability distributions over ontic states in a psi
      epistemic model. It is shown that in Hilbert spaces of dimension d>=4, the ratio
      between the classical and quantum overlaps in any psi-epistemic model must be
      arbitrarily small for certain nonorthogonal states, suggesting that such models
      are arbitrarily bad at explaining the indistinguishability of quantum states. For
      dimensions d=3 and 4, we construct explicit states and measurements that can be
      used experimentally to put stringent bounds on the ratio of classical-to-quantum
      overlaps in psi-epistemic models, allowing one in particular to rule out
      maximally psi-epistemic models more efficiently than previously proposed. 

PMID- 25062151
TI  - Discriminating single-photon states unambiguously in high dimensions.
AB  - The ability to uniquely identify a quantum state is integral to quantum science,
      but for nonorthogonal states, quantum mechanics precludes deterministic, error
      free discrimination. However, using the nondeterministic protocol of unambiguous
      state discrimination enables the error-free differentiation of states, at the
      cost of a lower frequency of success. We discriminate experimentally between
      nonorthogonal, high-dimensional states encoded in single photons; our results
      range from dimension d=2 to d=14. We quantify the performance of our method by
      comparing the total measured error rate to the theoretical rate predicted by
      minimum-error state discrimination. For the chosen states, we find a lower error
      rate by more than 1 standard deviation for dimensions up to d=12. This method
      will find immediate application in high-dimensional implementations of quantum
      information protocols, such as quantum cryptography. 

PMID- 25062152
TI  - Stringent and efficient assessment of boson-sampling devices.
AB  - Boson sampling holds the potential to experimentally falsify the extended Church
      Turing thesis. The computational hardness of boson sampling, however, complicates
      the certification that an experimental device yields correct results in the
      regime in which it outmatches classical computers. To certify a boson sampler,
      one needs to verify quantum predictions and rule out models that yield these
      predictions without true many-boson interference. We show that a semiclassical
      model for many-boson propagation reproduces coarse-grained observables that are
      proposed as witnesses of boson sampling. A test based on Fourier matrices is
      demonstrated to falsify physically plausible alternatives to coherent many-boson
      propagation. 

PMID- 25062153
TI  - Strain coupling of a nitrogen-vacancy center spin to a diamond mechanical
      oscillator.
AB  - We report on single electronic spins coupled to the motion of mechanical
      resonators by a novel mechanism based on crystal strain. Our device consists of
      single-crystal diamond cantilevers with embedded nitrogen-vacancy center spins.
      Using optically detected electron spin resonance, we determine the unknown spin
      strain coupling constants and demonstrate that our system resides well within the
      resolved sideband regime. We realize coupling strengths exceeding 10 MHz under
      mechanical driving and show that our system has the potential to reach strong
      coupling. Our novel hybrid system forms a resource for future experiments on spin
      based cantilever cooling and coherent spin-oscillator coupling. 

PMID- 25062154
TI  - Fundamental bounds in measurements for estimating quantum states.
AB  - Quantum measurement unavoidably disturbs the state of a quantum system if any
      information about the system is extracted. Recently, the concept of reversing
      quantum measurement has been introduced and has attracted much attention.
      Numerous efforts have thus been devoted to understanding the fundamental relation
      of the amount of information obtained by measurement to either state disturbance
      or reversibility. Here, we experimentally prove the trade-off relations in
      quantum measurement with respect to both state disturbance and reversibility. By
      demonstrating the quantitative bound of the trade-off relations, we realize an
      optimal measurement for estimating quantum systems with minimum disturbance and
      maximum reversibility. Our results offer fundamental insights on quantum
      measurement and practical guidelines for implementing various quantum information
      protocols. 

PMID- 25062155
TI  - Efficient quantum algorithm for computing n-time correlation functions.
AB  - We propose a method for computing n-time correlation functions of arbitrary
      spinorial, fermionic, and bosonic operators, consisting of an efficient quantum
      algorithm that encodes these correlations in an initially added ancillary qubit
      for probe and control tasks. For spinorial and fermionic systems, the
      reconstruction of arbitrary n-time correlation functions requires the measurement
      of two ancilla observables, while for bosonic variables time derivatives of the
      same observables are needed. Finally, we provide examples applicable to different
      quantum platforms in the frame of the linear response theory. 

PMID- 25062156
TI  - Fast room-temperature phase gate on a single nuclear spin in diamond.
AB  - Nuclear spins support long lived quantum coherence due to weak coupling to the
      environment, but are difficult to rapidly control using nuclear magnetic
      resonance as a result of the small nuclear magnetic moment. We demonstrate a fast
      ~500  ns nuclear spin phase gate on a (14)N nuclear spin qubit intrinsic to a
      nitrogen-vacancy center in diamond. The phase gate is enabled by the hyperfine
      interaction and off-resonance driving of electron spin transitions. Repeated
      applications of the phase gate bang-bang decouple the nuclear spin from the
      environment, locking the spin state for up to ~140  MUs.

PMID- 25062157
TI  - Steering most probable escape paths by varying relative noise intensities.
AB  - We demonstrate the possibility to systematically steer the most probable escape
      paths (MPEPs) by adjusting relative noise intensities in dynamical systems that
      exhibit noise-induced escape from a metastable point via a saddle point. With the
      use of a geometric minimum action approach, an asymptotic theory is developed
      that is broadly applicable to fast-slow systems and shows the important role
      played by the nullcline associated with the fast variable in locating the MPEPs.
      A two-dimensional quadratic system is presented which permits analytical
      determination of both the MPEPs and associated action values. Analytical
      predictions agree with computed MPEPs, and both are numerically confirmed by
      constructing prehistory distributions directly from the underlying stochastic
      differential equation. 

PMID- 25062158
TI  - Breakdown of the generalized Gibbs ensemble for current-generating quenches.
AB  - We establish a relation between two hallmarks of integrable systems: the
      relaxation towards the generalized Gibbs ensemble (GGE) and the dissipationless
      charge transport. We show that the former one is possible only if the so-called
      Mazur bound on the charge stiffness is saturated by local conserved quantities.
      As an example we show how a non-GGE steady state with a current can be generated
      in the one-dimensional model of interacting spinless fermions with a flux quench.
      Moreover, an extended GGE involving the quasilocal conserved quantities can be
      formulated for this case. 

PMID- 25062159
TI  - Multiple scattering tomography.
AB  - Multiple scattering represents a challenge for numerous modern tomographic
      imaging techniques. In this Letter, we derive an appropriate line integral that
      allows for the tomographic reconstruction of angular resolved scattering
      distributions, even in the presence of multiple scattering. The line integral is
      applicable to a wide range of imaging techniques utilizing various kinds of
      probes. Here, we use x-ray grating interferometry to experimentally validate the
      framework and to demonstrate additional structural sensitivity, which exemplifies
      the impact of multiple scattering tomography. 

PMID- 25062160
TI  - Sparse representations of gravitational waves from precessing compact binaries.
AB  - Many relevant applications in gravitational wave physics share a significant
      common problem: the seven-dimensional parameter space of gravitational waveforms
      from precessing compact binary inspirals and coalescences is large enough to
      prohibit covering the space of waveforms with sufficient density. We find that by
      using the reduced basis method together with a parametrization of waveforms based
      on their phase and precession, we can construct ultracompact yet high-accuracy
      representations of this large space. As a demonstration, we show that less than
      100 judiciously chosen precessing inspiral waveforms are needed for 200 cycles,
      mass ratios from 1 to 10, and spin magnitudes <=0.9. In fact, using only the
      first 10 reduced basis waveforms yields a maximum mismatch of 0.016 over the
      whole range of considered parameters. We test whether the parameters selected
      from the inspiral regime result in an accurate reduced basis when including
      merger and ringdown; we find that this is indeed the case in the context of a
      nonprecessing effective-one-body model. This evidence suggests that as few as
      ~100 numerical simulations of binary black hole coalescences may accurately
      represent the seven-dimensional parameter space of precession waveforms for the
      considered ranges. 

PMID- 25062162
TI  - Tying dark matter to baryons with self-interactions.
AB  - Self-interacting dark matter (SIDM) models have been proposed to solve the small
      scale issues with the collisionless cold dark matter paradigm. We derive
      equilibrium solutions in these SIDM models for the dark matter halo density
      profile including the gravitational potential of both baryons and dark matter.
      Self-interactions drive dark matter to be isothermal and this ties the core sizes
      and shapes of dark matter halos to the spatial distribution of the stars, a
      radical departure from previous expectations and from cold dark matter
      predictions. Compared to predictions of SIDM-only simulations, the core sizes are
      smaller and the core densities are higher, with the largest effects in baryon
      dominated galaxies. As an example, we find a core size around 0.3 kpc for dark
      matter in the Milky Way, more than an order of magnitude smaller than the core
      size from SIDM-only simulations, which has important implications for indirect
      searches of SIDM candidates. 

PMID- 25062163
TI  - Quantum spectral curve of the N=6 supersymmetric Chern-Simons theory.
AB  - Recently, it was shown that the spectrum of anomalous dimensions and other
      important observables in planar N=4 supersymmetric Yang-Mills theory are encoded
      into a simple nonlinear Riemann-Hilbert problem: the PMU system or quantum
      spectral curve. In this Letter, we extend this formulation to the N=6
      supersymmetric Chern-Simons theory introduced by Aharony, Bergman, Jafferis, and
      Maldacena. This may be an important step towards the exact determination of the
      interpolating function h(lambda) characterizing the integrability of this model.
      We also discuss a surprising relation between the quantum spectral curves for the
      N=4 supersymmetric Yang-Mills theory and the N=6 supersymmetric Chern-Simons
      theory considered here. 

PMID- 25062161
TI  - Measurement of the cosmic microwave background polarization lensing power
      spectrum with the POLARBEAR experiment.
AB  - Gravitational lensing due to the large-scale distribution of matter in the cosmos
      distorts the primordial cosmic microwave background (CMB) and thereby induces
      new, small-scale B-mode polarization. This signal carries detailed information
      about the distribution of all the gravitating matter between the observer and CMB
      last scattering surface. We report the first direct evidence for polarization
      lensing based on purely CMB information, from using the four-point correlations
      of even- and odd-parity E- and B-mode polarization mapped over ~30 square degrees
      of the sky measured by the POLARBEAR experiment. These data were analyzed using a
      blind analysis framework and checked for spurious systematic contamination using
      null tests and simulations. Evidence for the signal of polarization lensing and
      lensing B modes is found at 4.2sigma (stat+sys) significance. The amplitude of
      matter fluctuations is measured with a precision of 27%, and is found to be
      consistent with the Lambda cold dark matter cosmological model. This measurement
      demonstrates a new technique, capable of mapping all gravitating matter in the
      Universe, sensitive to the sum of neutrino masses, and essential for cleaning the
      lensing B-mode signal in searches for primordial gravitational waves. 

PMID- 25062164
TI  - Geometrical hierarchies in classical supergravity.
AB  - We introduce a N=1 supergravity model with a very simple hidden sector coupled to
      the electroweak gauge and Higgs sectors of the minimal supersymmetric standard
      model. At the classical level, supersymmetry and SU(2)*U(1) are both
      spontaneously broken, with vanishing vacuum energy. Two real flat directions
      control the two symmetry-breaking scales m(3/2) and m(Z). The two massless
      scalars are a gauge singlet and the standard Higgs boson. All other unobserved
      particles have masses of order m(3/2). This may be a new starting point for
      studying the compatibility of naturalness with the observed mass hierarchies.

PMID- 25062165
TI  - Fragmentation contributions to J/psi production at the Tevatron and the LHC.
AB  - We compute leading-power fragmentation corrections to J/psi production at the
      Tevatron and the LHC. We find that, when these corrections are combined with
      perturbative corrections through next-to-leading order in the strong coupling
      constant alpha(s), we obtain a good fit to high-p(T) cross section data from the
      CDF and CMS Collaborations. The fitted long-distance matrix elements lead to
      predictions of near-zero J/psi polarization in the helicity frame at large p(T).

PMID- 25062166
TI  - Precision measurement of the neutron twist-3 matrix element d(2)(n): probing
      color forces.
AB  - Double-spin asymmetries and absolute cross sections were measured at large
      Bjorken x  (0.25<=x<=0.90), in both the deep-inelastic and resonance regions, by
      scattering longitudinally polarized electrons at beam energies of 4.7 and 5.9 GeV
      from a transversely and longitudinally polarized (3)He target. In this dedicated
      experiment, the spin structure function g(2)((3)He) was determined with precision
      at large x, and the neutron twist-3 matrix element d(2)(n) was measured at ?Q(2)?
      of 3.21 and 4.32  GeV(2)/c(2), with an absolute precision of about 10(-5). Our
      results are found to be in agreement with lattice QCD calculations and resolve
      the disagreement found with previous data at ?Q(2)?=5  GeV(2)/c(2). Combining
      d(2)(n) and a newly extracted twist-4 matrix element f(2)(n), the average neutron
      color electric and magnetic forces were extracted and found to be of opposite
      sign and about 30  MeV/fm in magnitude.

PMID- 25062170
TI  - Fusion hindrance for a positive-q-value system (24)Mg+(30)Si.
AB  - Measurements of the excitation function for the fusion of (24)Mg+(30)Si (Q=17.89 
      MeV)have been extended toward lower energies with respect to previous
      experimental data. The S-factor maximum observed in this large, positive-Q-value
      system is the most pronounced among such systems studied thus far. The
      significance and the systematics of an S-factor maximum in systems with positive
      fusion Q values are discussed. This result would strongly impact the extrapolated
      cross sections and reaction rates in the carbon and oxygen burnings and, thus,
      the study of the history of stellar evolution.

PMID- 25062172
TI  - Two-pulse field-free orientation reveals anisotropy of molecular shape resonance.
AB  - We report the observation of macroscopic field-free orientation, i.e., more than
      73% of CO molecules pointing in the same direction. This is achieved through an
      all-optical scheme operating at high particle densities (>10(17)  cm(-3)) that
      combines one-color (omega) and two-color (omega+2omega) nonresonant femtosecond
      laser pulses. We show that the achieved orientation solely relies on the
      hyperpolarizability interaction as opposed to an ionization-depletion mechanism,
      thus, opening a wide range of applications. The achieved strong orientation
      enables us to reveal the molecular-frame anisotropies of the photorecombination
      amplitudes and phases caused by a shape resonance. The resonance appears as a
      local maximum in the even-harmonic emission around 28 eV. In contrast, the odd
      harmonic emission is suppressed in this spectral region through the combined
      effects of an asymmetric photorecombination phase and a subcycle Stark effect,
      generic for polar molecules, that we experimentally identify.

PMID- 25062171
TI  - Half-life systematics across the N=126 shell closure: role of first-forbidden
      transitions in the beta decay of heavy neutron-rich nuclei.
AB  - This Letter reports on a systematic study of beta-decay half-lives of neutron
      rich nuclei around doubly magic (208)Pb. The lifetimes of the 126-neutron shell
      isotone (204)Pt and the neighboring (200-202)Ir, (203)Pt, (204)Au are presented
      together with other 19 half-lives measured during the "stopped beam" campaign of
      the rare isotope investigations at GSI collaboration. The results constrain the
      main nuclear theories used in calculations of r-process nucleosynthesis.
      Predictions based on a statistical macroscopic description of the first-forbidden
      beta strength reveal significant deviations for most of the nuclei with N<126. In
      contrast, theories including a fully microscopic treatment of allowed and first
      forbidden transitions reproduce more satisfactorily the trend in the measured
      half-lives for the nuclei in this region, where the r-process pathway passes
      through during beta decay back to stability.

PMID- 25062168
TI  - Probing the repulsive core of the nucleon-nucleon interaction via the
      (4)He(e,e'pN) triple-coincidence reaction.
AB  - We studied simultaneously the (4)He(e,e'p), (4)He(e,e'pp), and (4)He(e,e'pn)
      reactions at Q(2)=2(GeV/c)(2) and x(B)>1, for an (e,e'p) missing-momentum range
      of 400 to 830  MeV/c. The knocked-out proton was detected in coincidence with a
      proton or neutron recoiling almost back to back to the missing momentum, leaving
      the residual A=2 system at low excitation energy. These data were used to
      identify two-nucleon short-range correlated pairs and to deduce their isospin
      structure as a function of missing momentum, in a region where the nucleon
      nucleon (NN) force is expected to change from predominantly tensor to repulsive.
      The abundance of neutron-proton pairs is reduced as the nucleon momentum
      increases beyond ~500  MeV/c. The extracted fraction of proton-proton pairs is
      small and almost independent of the missing momentum. Our data are compared with
      calculations of two-nucleon momentum distributions in (4)He and discussed in the
      context of probing the elusive repulsive component of the NN force.

PMID- 25062173
TI  - Nuclear polarization study: new frontiers for tests of QED in heavy highly
      charged ions.
AB  - A systematic investigation of the nuclear polarization effects in one- and few
      electron heavy ions is presented. The nuclear polarization corrections in the
      zeroth and first orders in 1/Z are evaluated to the binding energies, the
      hyperfine splitting, and the bound-electron g factor. It is shown that the
      nuclear polarization contributions can be substantially canceled simultaneously
      with the rigid nuclear corrections. This allows for new prospects for probing the
      QED effects in a strong electromagnetic field and the determination of
      fundamental constants. 

PMID- 25062174
TI  - Multimode Kapitza-Dirac interferometry with trapped cold atoms.
AB  - We design a multimode interferometer with cold atoms confined in a harmonic trap.
      A first Kapitza-Dirac pulse creates several spatially addressable modes which are
      coherently recombined by the harmonic potential and mixed again by a second
      Kapitza-Dirac pulse. A phase shift among the mode is estimated by fitting the
      density profile or by measuring the number of atoms in each output mode. The
      expected sensitivity is rigorously calculated with the Fisher information and the
      Cramer-Rao lower bound. For the measurement of the gravitational acceleration g
      we predict, with typical parameters of a compact setup, a temperature independent
      sensitivity which can exceed, by several orders of magnitude, the sensitivity of
      current atomic interferometers. 

PMID- 25062175
TI  - Simplest molecules as candidates for precise optical clocks.
AB  - The precise measurement of transition frequencies in cold, trapped molecules has
      applications in fundamental physics, and extremely high accuracies are desirable.
      We determine suitable candidates by considering the simplest molecules with a
      single electron, for which the external-field shift corrections can be calculated
      theoretically with high precision. Our calculations show that H(2)(+) exhibits
      particular transitions whose fractional systematic uncertainties may be reduced
      to 5*10(-17) at room temperature. We also generalize the method of composite
      frequencies, introducing tailored linear combinations of individual transition
      frequencies that are free of the major systematic shifts, independent of the
      strength of the external perturbing fields. By applying this technique, the
      uncertainty of the composite frequency is reduced compared to what is achievable
      with a single transition, e.g., to the 10(-18) range for HD(+). Thus, these
      molecules are of metrological relevance for future studies.

PMID- 25062176
TI  - Test of Einstein equivalence principle for 0-spin and half-integer-spin atoms:
      search for spin-gravity coupling effects.
AB  - We report on a conceptually new test of the equivalence principle performed by
      measuring the acceleration in Earth's gravity field of two isotopes of strontium
      atoms, namely, the bosonic (88)Sr isotope which has no spin versus the fermionic
      (87)Sr isotope which has a half-integer spin. The effect of gravity on the two
      atomic species has been probed by means of a precision differential measurement
      of the Bloch frequency for the two atomic matter waves in a vertical optical
      lattice. We obtain the values eta=(0.2+/-1.6)*10(-7) for the Eotvos parameter and
      k=(0.5+/-1.1)*10(-7) for the coupling between nuclear spin and gravity. This is
      the first reported experimental test of the equivalence principle for bosonic and
      fermionic particles and opens a new way to the search for the predicted spin
      gravity coupling effects.

PMID- 25062169
TI  - Measurement of the target-normal single-spin asymmetry in deep-inelastic
      scattering from the reaction (3)He(?)(e,e')X.
AB  - We report the first measurement of the target-normal single-spin asymmetry in
      deep-inelastic scattering from the inclusive reaction 3)He(?)(e,e')X on a
      polarized (3)He gas target. Assuming time-reversal invariance, this asymmetry is
      strictly zero in the Born approximation but can be nonzero if two-photon-exchange
      contributions are included. The experiment, conducted at Jefferson Lab using a
      5.89 GeV electron beam, covers a range of 1.7<W<2.9  GeV, 1.0<Q(2)<4.0  GeV(2)
      and 0.16<x<0.65. Neutron asymmetries were extracted using the effective nucleon
      polarization and measured proton-to-(3)He cross-section ratios. The measured
      neutron asymmetries are negative with an average value of (-1.09+/-0.38)*10(-2)
      for invariant mass W>2  GeV, which is nonzero at the 2.89sigma level. Our
      measured asymmetry agrees both in sign and magnitude with a two-photon-exchange
      model prediction that uses input from the Sivers transverse momentum distribution
      obtained from semi-inclusive deep-inelastic scattering.

PMID- 25062177
TI  - Full counting statistics and phase diagram of a dissipative Rydberg gas.
AB  - Ultracold gases excited to strongly interacting Rydberg states are a promising
      system for quantum simulations of many-body systems. For off-resonant excitation
      of such systems in the dissipative regime, highly correlated many-body states
      exhibiting, among other characteristics, intermittency and multimodal counting
      distributions are expected to be created. Here we report on the realization of a
      dissipative gas of rubidium Rydberg atoms and on the measurement of its full
      counting statistics and phase diagram for both resonant and off-resonant
      excitation. We find strongly bimodal counting distributions in the off-resonant
      regime that are compatible with intermittency due to the coexistence of dynamical
      phases. Our results pave the way towards detailed studies of many-body effects in
      Rydberg gases. 

PMID- 25062178
TI  - Optomechanical Rydberg-atom excitation via dynamic Casimir-Polder coupling.
AB  - We study the optomechanical coupling of a oscillating effective mirror with a
      Rydberg atomic gas, mediated by the dynamical atom-mirror Casimir-Polder force.
      This coupling may produce a near-field resonant atomic excitation whose
      probability scales as ?(d(2)an(4)t)(2)/z(0)(8), where z(0) is the average atom
      surface distance, d the atomic dipole moment, a the mirror's effective
      oscillation amplitude, n the initial principal quantum number, and t the time. We
      propose an experimental configuration to realize this system with a cold atom gas
      trapped at a distance ~2*10  MUm from a semiconductor substrate whose dielectric
      constant is periodically driven by an external laser pulse, hence realizing an
      effective mechanical mirror motion due to the periodic change of the substrate
      from transparent to reflecting. For a parabolic gas shape, this effect is
      predicted to excite about ~10(2) atoms of a dilute gas of 10(3) trapped Rydberg
      atoms with n=75 after about 0.5  MUs, which is high enough to be detected in
      typical Rydberg gas experimental conditions.

PMID- 25062179
TI  - Experimental generation of multiple quantum correlated beams from hot rubidium
      vapor.
AB  - Quantum correlations and entanglement shared among multiple quantum modes are
      important for both fundamental science and the future development of quantum
      technologies. This development will also require an efficient quantum interface
      between multimode quantum light sources and atomic ensembles, which makes it
      necessary to implement multimode quantum light sources that match the atomic
      transitions. Here, we report on such a source that provides a method for
      generating quantum correlated beams that can be extended to a large number of
      modes by using multiple four-wave mixing (FWM) processes in hot rubidium vapor.
      Experimentally, we show that two cascaded FWM processes produce strong quantum
      correlations between three bright beams but not between any two of them. In
      addition, the intensity-difference squeezing is enhanced with the cascaded system
      to -7.0+/-0.1  dB from the -5.5+/-0.1/-4.5+/-0.1  dB squeezing obtained with only
      one FWM process. One of the main advantages of our system is that as the number
      of quantum modes increases, so does the total degree of quantum correlations. The
      proposed method is also immune to phase instabilities due to its phase
      insensitive nature, can easily be extended to multiple modes, and has potential
      applications in the production of multiple quantum correlated images. 

PMID- 25062180
TI  - Implementation of the Dicke lattice model in hybrid quantum system arrays.
AB  - Generalized Dicke models can be implemented in hybrid quantum systems built from
      ensembles of nitrogen-vacancy (NV) centers in diamond coupled to superconducting
      microwave cavities. By engineering cavity assisted Raman transitions between two
      spin states of the NV defect, a fully tunable model for collective light-matter
      interactions in the ultrastrong coupling limit can be obtained. Our analysis of
      the resulting nonequilibrium phases for a single cavity and for coupled cavity
      arrays shows that different superradiant phase transitions can be observed using
      existing experimental technologies, even in the presence of large inhomogeneous
      broadening of the spin ensemble. The phase diagram of the Dicke lattice model
      displays distinct features induced by dissipation, which can serve as a genuine
      experimental signature for phase transitions in driven open quantum systems. 

PMID- 25062181
TI  - Quantum-limited amplification and parametric instability in the reversed
      dissipation regime of cavity optomechanics.
AB  - Cavity optomechanical phenomena, such as cooling, amplification, or
      optomechanically induced transparency, emerge due to a strong imbalance in the
      dissipation rates of the parametrically coupled electromagnetic and mechanical
      resonators. Here we analyze the reversed dissipation regime where the mechanical
      energy relaxation rate exceeds the energy decay rate of the electromagnetic
      cavity. We demonstrate that this regime allows for mechanically induced
      amplification (or cooling) of the electromagnetic mode. Gain, bandwidth, and
      added noise of this electromagnetic amplifier are derived and compared to
      amplification in the normal dissipation regime. In addition, we analyze the
      parametric instability, i.e., optomechanical Brillouin lasing, and contrast it to
      conventional optomechanical phonon lasing. Finally, we propose an experimental
      scheme that realizes the reversed dissipation regime using parametric coupling
      and optomechanical cooling with a second electromagnetic mode enabling quantum
      limited amplification. Recent advances in high-Q superconducting microwave
      resonators make the reversed dissipation regime experimentally realizable. 

PMID- 25062182
TI  - Bistability with optical beams propagating in a reorientational medium.
AB  - We investigated bistability with light beams in reorientational nematic liquid
      crystals. For a range of input powers, beams can propagate as either diffracting
      or self-trapped, the latter corresponding to spatial solitons. The first-order
      transition in samples exhibiting abrupt self-focusing with a threshold is in
      agreement with a simple model. 

PMID- 25062183
TI  - High performance bianisotropic metasurfaces: asymmetric transmission of light.
AB  - It is experimentally shown that bianisotropic metasurfaces allow for extreme
      polarization control of light with high performance. A metasurface providing
      asymmetric transmission (i.e., polarization conversion) of circularly polarized
      light is reported at a wavelength of 1.5  MUm. The experimental transmittance and
      extinction ratio are 50% and 20:1, which represents an order of magnitude
      improvement over previous optical structures exhibiting asymmetric transmission.
      The metasurface consists of patterned gold sheets that are spaced at a
      subwavelength distance from each other. The same design and fabrication processes
      can be used in the future to completely control the phase, amplitude, and
      polarization of light. 

PMID- 25062184
TI  - Negative refraction and planar focusing based on parity-time symmetric
      metasurfaces.
AB  - We introduce a new mechanism to realize negative refraction and planar focusing
      using a pair of parity-time symmetric metasurfaces. In contrast to existing
      solutions that achieve these effects with negative-index metamaterials or phase
      conjugating surfaces, the proposed parity-time symmetric lens enables loss-free,
      all-angle negative refraction and planar focusing in free space, without relying
      on bulk metamaterials or nonlinear effects. This concept may represent a pivotal
      step towards loss-free negative refraction and highly efficient planar focusing
      by exploiting the largely uncharted scattering properties of parity-time
      symmetric systems. 

PMID- 25062167
TI  - Dielectron mass spectra from Au+Au collisions at ?[s(NN)]=200  GeV.
AB  - We report the STAR measurements of dielectron (e(+)e(-)) production at
      midrapidity (|y(ee)|<1) in Au+Au collisions at ?[s(NN)]=200  GeV. The
      measurements are evaluated in different invariant mass regions with a focus on
      0.30-0.76 (rho-like), 0.76-0.80 (omega-like), and 0.98-1.05 (phi-like)  
      GeV/c(2). The spectrum in the omega-like and phi-like regions can be well
      described by the hadronic cocktail simulation. In the rho-like region, however,
      the vacuum rho spectral function cannot describe the shape of the dielectron
      excess. In this range, an enhancement of 1.77+/-0.11(stat)+/-0.24(syst)+/
      0.33(cocktail) is determined with respect to the hadronic cocktail simulation
      that excludes the rho meson. The excess yield in the rho-like region increases
      with the number of collision participants faster than the omega and phi yields.
      Theoretical models with broadened rho contributions through interactions with
      constituents in the hot QCD medium provide a consistent description of the
      dilepton mass spectra for the measurement presented here and the earlier data at
      the Super Proton Synchrotron energies.

PMID- 25062185
TI  - Self-amplified gamma-ray laser on positronium atoms from a Bose-Einstein
      condensate.
AB  - A scheme of an intense coherent gamma-ray source based on the spontaneous
      radiation of positronium atoms in a Bose-Einstein condensate (BEC) due to two
      photon collective annihilation decay is investigated analytically arising from
      the second quantized formalism. It is shown that because of the intrinsic
      instability of annihilation decay of BEC, the spontaneously emitted entangled
      photon pairs are amplified, leading to an exponential buildup of a macroscopic
      population into end-fire modes at a certain shape of the elongated condensate.
      The considered scheme may also be applied to a BEC of atoms or quasiparticles as
      a laser mechanism with double coherence to create entangled photonic beams with a
      macroscopic number of photons. 

PMID- 25062186
TI  - Collision time measurements in a sonoluminescing microplasma with a large plasma
      parameter.
AB  - The plasma which forms inside of a micron-sized sonoluminescing bubble in water
      for under a nanosecond has been probed with 3 ns long laser pulses. A comparison
      of the response to 532 and 1064 nm light indicates that the plasma number density
      is about 2*10(21)  cm(-3) and that transport properties are dominated by strong
      screening and correlation effects. The spherical shape, well-defined atomic
      density, and blackbody temperature make the sonoluminescing plasma a test bed for
      theories of strongly coupled plasmas. The plasma in this experiment distinguishes
      between competing theories of strong, intermediate, and weak effective screening.

PMID- 25062187
TI  - New type of anomaly in turbulence.
AB  - The turbulent energy flux through scales, epsilon, remains constant and
      nonvanishing in the limit of zero viscosity, which results in the fundamental
      anomaly of time irreversibility. It was considered straightforward to deduce from
      this the Lagrangian velocity anomaly, ?du(2)/dt?=-4epsilon at t=0, where u[over 
      >] is the velocity difference of a pair of particles, initially separated by a
      fixed distance. Here we demonstrate that this assumed first taking the limit t->0
      and then nu->0, while a zero-friction anomaly requires taking viscosity to zero
      first. We find that the limits t->0 and nu->0 do not commute if particles deplete
      (accumulate) in shocks backward (forward) in time on the viscous time scale. We
      compute analytically the resultant Lagrangian anomaly for one-dimensional Burgers
      turbulence and find it completely altered: ?du(2)/dt? has different values
      forward and backward in time. For incompressible flows, on the other hand, we
      show that the limits commute and the Lagrangian anomaly is still induced by the
      flux law, apparently due to a homogeneous distribution of fluid particles at all
      times.

PMID- 25062188
TI  - Hydrodynamic fingering instability induced by a precipitation reaction.
AB  - We experimentally demonstrate that a precipitation reaction at the miscible
      interface between two reactive solutions can trigger a hydrodynamic instability
      due to the buildup of a locally adverse mobility gradient related to a decrease
      in permeability. The precipitate results from an A+B->C type of reaction when a
      solution containing one of the reactants is injected into a solution of the other
      reactant in a porous medium or a Hele-Shaw cell. Fingerlike precipitation
      patterns are observed upon displacement, the properties of which depend on
      whether A displaces B or vice versa. A mathematical modeling of the underlying
      mobility profile confirms that the instability originates from a local decrease
      in mobility driven by the localized precipitation. Nonlinear simulations of the
      related reaction-diffusion-convection model reproduce the properties of the
      instability observed experimentally. In particular, the simulations suggest that
      differences in diffusivity between A and B may contribute to the asymmetric
      characteristics of the fingering precipitation patterns. 

PMID- 25062189
TI  - Facilitated ignition in turbulence through differential diffusion.
AB  - Contrary to the belief that ignition of a combustible mixture by a high-energy
      kernel is more difficult in turbulence than in quiescence because of the
      increased dissipation rate of the deposited energy, we experimentally demonstrate
      that it can actually be facilitated by turbulence for mixtures whose thermal
      diffusivity sufficiently exceeds its mass diffusivity. In such cases, turbulence
      breaks the otherwise single spherical flame of positive curvature, and hence
      positive aerodynamics stretch, into a multitude of wrinkled flamelets subjected
      to either positive or negative stretch, such that the intensified burning of the
      latter constitutes local sources to facilitate ignition. 

PMID- 25062190
TI  - Scaling of near-wall flows in quasi-two-dimensional turbulent channels.
AB  - The law of the wall and the log law rule the near-wall mean velocity profile of
      three-dimensional turbulent flows. These well-known laws, which are validated by
      legions of experiments and simulations, may be universal. Here, using a soap-film
      channel, we report the first experimental test of these laws in quasi-two
      dimensional turbulent channel flows under two disparate turbulent spectra. We
      find that despite the differences with three-dimensional flows, the laws prevail,
      albeit with notable distinctions: the two parameters of the log law are markedly
      distinct from their three-dimensional counterpart; further, one parameter (the
      von Karman constant) is independent of the spectrum whereas the other (the offset
      of the log law) depends on the spectrum. Our results suggest that the classical
      theory of scaling in wall-bounded turbulence is incomplete wherein a key missing
      element is the link with the turbulent spectrum. 

PMID- 25062191
TI  - Experimental evidence for nonaxisymmetric magnetorotational instability in a
      rotating liquid metal exposed to an azimuthal magnetic field.
AB  - The azimuthal version of the magnetorotational instability (MRI) is a
      nonaxisymmetric instability of a hydrodynamically stable differentially rotating
      flow under the influence of a purely or predominantly azimuthal magnetic field.
      It may be of considerable importance for destabilizing accretion disks, and plays
      a central role in the concept of the MRI dynamo. We report the results of a
      liquid metal Taylor-Couette experiment that shows the occurrence of an azimuthal
      MRI in the expected range of Hartmann numbers. 

PMID- 25062192
TI  - Superheating and homogeneous single bubble nucleation in a solid-state nanopore.
AB  - We demonstrate extreme superheating and single bubble nucleation in an
      electrolyte solution within a nanopore in a thin silicon nitride membrane. The
      high temperatures are achieved by Joule heating from a highly focused ionic
      current induced to flow through the pore by modest voltage biases. Conductance,
      nucleation, and bubble evolution are monitored electronically and optically.
      Temperatures near the thermodynamic limit of superheat are achieved just before
      bubble nucleation with the system at atmospheric pressure. Bubble nucleation is
      homogeneous and highly reproducible. This nanopore approach more generally
      suggests broad application to the excitation, detection, and characterization of
      highly metastable states of matter. 

PMID- 25062193
TI  - Experiments of drops impacting a smooth solid surface: a model of the critical
      impact speed for drop splashing.
AB  - Making use of experimental and theoretical considerations, in this Letter we
      deduce a criterion to determine the critical velocity for which a drop impacting
      a smooth dry surface either spreads over the substrate or disintegrates into
      smaller droplets. The derived equation, which expresses the splash threshold
      velocity as a function of the material properties of the two fluids involved, the
      drop radius, and the mean free path of the molecules composing the surrounding
      gaseous atmosphere, has been thoroughly validated experimentally at normal
      atmospheric conditions using eight different liquids with viscosities ranging
      from MU=3*10(-4) to MU=10(-2)  Pa s, and interfacial tension coefficients varying
      between sigma=17 and sigma=72  mN m(-1). Our predictions are also in fair
      agreement with the measured critical speed of drops impacting in different gases
      at reduced pressures given by Xu et al. [Phys. Rev. Lett. 94, 184505 (2005).

PMID- 25062194
TI  - Free-electron laser design for four-wave mixing experiments with soft-x-ray
      pulses.
AB  - We present the design of a single-pass free-electron laser amplifier suitable for
      enabling four-wave mixing x-ray spectroscopic investigations. The production of
      longitudinally coherent, single-spike pulses of light from a single electron beam
      in this scenario relies on a process of selective amplification where a strong
      undulator taper compensates for a large energy chirp only for a short region of
      the electron beam. This proposed scheme offers improved flexibility of operation
      and allows for independent control of the color, timing, and angle of incidence
      of the individual pulses of light at an end user station. Detailed numerical
      simulations are used to illustrate the more impressive characteristics of this
      scheme. 

PMID- 25062195
TI  - First observation of a (1,0) mode frequency shift of an electron plasma at
      antiproton beam injection.
AB  - The frequency shift of the center-of-mass oscillation, known as the (1,0) mode,
      of a trapped electron plasma and, furthermore, its time evolution were observed
      during the cooling of an injected antiproton beam for the first time. Here,
      antiprotons mixed with the electrons did not follow faster electron oscillations
      but contributed to the modification of the effective potential. The time
      evolution of the plasma temperature, deduced from the frequency shift of the
      excited (3,0) mode, suggested that there was an abnormal energy deposition of the
      antiproton beam in the electron plasma before thermalization. 

PMID- 25062196
TI  - Slow plastic creep of 2D dusty plasma solids.
AB  - We report complex plasma experiments, assisted by numerical simulations,
      providing an alternative qualitative link between the macroscopic response of
      polycrystalline solid matter to small shearing forces and the possible underlying
      microscopic processes. In the stationary creep regime we have determined the
      exponents of the shear rate dependence of the shear stress and defect density,
      being alpha=1.15+/-0.1 and beta=2.4+/-0.4, respectively. We show that the
      formation and rapid glide motion of dislocation pairs in the lattice are dominant
      processes. 

PMID- 25062197
TI  - Linear technique to understand non-normal turbulence applied to a magnetized
      plasma.
AB  - In nonlinear dynamical systems with highly nonorthogonal linear eigenvectors,
      linear nonmodal analysis is more useful than normal mode analysis in predicting
      turbulent properties. However, the nontrivial time evolution of nonmodal
      structures makes quantitative understanding and prediction difficult. We present
      a technique to overcome this difficulty by modeling the effect that the advective
      nonlinearities have on spatial turbulent structures. The nonlinearities are taken
      as a periodic randomizing force with time scale consistent with critical balance
      arguments. We apply this technique to a model of drift wave turbulence in the
      Large Plasma Device [W. Gekelman et al., Rev. Sci. Instrum. 62, 2875 (1991)],
      where nonmodal effects dominate the turbulence. We compare the resulting growth
      rate spectra to the spectra obtained from a nonlinear simulation, showing good
      qualitative agreement, especially in comparison to the eigenmode growth rate
      spectra. 

PMID- 25062198
TI  - Electron plasma orbits from competing diocotron drifts.
AB  - The perpendicular dynamics of a pure electron plasma column are investigated when
      the plasma spans two Penning-Malmberg traps with noncoinciding axes. The plasma
      executes noncircular orbits described by competing image-charge electric-field
      (diocotron) drifts from the two traps. A simple model is presented that predicts
      a set of nested orbits in agreement with observed plasma trajectories. 

PMID- 25062199
TI  - Plasma-based generation and control of a single few-cycle high-energy ultrahigh
      intensity laser pulse.
AB  - A laser-boosted relativistic solid-density paraboloidal foil is known to
      efficiently reflect and focus a counterpropagating laser pulse. Here we show that
      in the case of an ultrarelativistic counterpropagating pulse, a high-energy and
      ultrahigh-intensity reflected pulse can be more effectively generated by a
      relatively slow and heavy foil than by a fast and light one. This
      counterintuitive result is explained with the larger reflectivity of a heavy
      foil, which compensates for its lower relativistic Doppler factor. Moreover,
      since the counterpropagating pulse is ultrarelativistic, the foil is abruptly
      dispersed and only the first few cycles of the counterpropagating pulse are
      reflected. Our multidimensional particle-in-cell simulations show that even few
      cycle counterpropagating laser pulses can be further shortened (both temporally
      and in the number of laser cycles) with pulse amplification. A single few-cycle,
      multipetawatt laser pulse with several joules of energy and with a peak intensity
      exceeding 10(23)  W/cm(2) can be generated already employing next-generation high
      power laser systems. In addition, the carrier-envelope phase of the generated few
      cycle pulse can be tuned provided that the carrier-envelope phase of the initial
      counterpropagating pulse is controlled.

PMID- 25062200
TI  - Nonmodal growth of the magnetorotational instability.
AB  - We analyze the linear growth of the magnetorotational instability (MRI) in the
      short-time limit using nonmodal methods. Our findings are quite different from
      standard results, illustrating that shearing wave energy can grow at the maximum
      MRI rate -dOmega/dlnr for any choice of azimuthal and vertical wavelengths. In
      addition, by comparing the growth of shearing waves with static structures, we
      show that over short time scales shearing waves will always be dynamically more
      important than static structures in the ideal limit. By demonstrating that fast
      linear growth is possible at all wavelengths, these results suggest that nonmodal
      linear physics could play a fundamental role in MRI turbulence. 

PMID- 25062201
TI  - Optimal persistent currents for interacting bosons on a ring with a gauge field.
AB  - We study persistent currents for interacting one-dimensional bosons on a tight
      ring trap, subjected to a rotating barrier potential, which induces an artificial
      U(1) gauge field. We show that, at intermediate interactions, the persistent
      current response is maximal, due to a subtle interplay of effects due to the
      barrier, the interaction, and quantum fluctuations. These results are relevant
      for ongoing experiments with ultracold atomic gases on mesoscopic rings. 

PMID- 25062202
TI  - Tuning ultracold chemical reactions via Rydberg-dressed interactions.
AB  - We show that ultracold chemical reactions with an activation barrier can be tuned
      using Rydberg-dressed interactions. Scattering in the ultracold regime is
      sensitive to long-range interactions, especially when weakly bound (or
      quasibound) states exist near the collision threshold. We investigate how, by
      Rydberg dressing a reactant, one enhances its polarizability and modifies the
      long-range van der Waals collision complex, which can alter chemical reaction
      rates by shifting the position of near-threshold bound states. We carry out a
      full quantum mechanical scattering calculation for the benchmark system H(2)+D,
      and show that resonances can be moved substantially and that rate coefficients at
      cold and ultracold temperatures can be increased by several orders of magnitude.

PMID- 25062203
TI  - Origin of anomalous slip in tungsten.
AB  - Low-temperature deformation of body-centered cubic metals shows a significant
      amount of plastic slip on planes with low shear stresses, a phenomenon called
      anomalous slip. Despite progress in atomistic modeling of the consequences of
      complex stress states on dislocation mobility, the phenomenon of anomalous slip
      remained elusive. Using in situ Laue microdiffraction and discrete dislocation
      dynamics in micrometer sized tungsten single crystals, we demonstrate the
      occurrence of significant anomalous slip. It occurs as a consequence of cross
      kinks, topological configurations generated by prior dislocation interactions.
      This clearly identifies anomalous slip as a multidislocation process and not a
      property of isolated dislocations. The cross-kink mechanism also explains the
      ambiguous reporting of anomalous slip traces in the past and directs us to ways
      of including anomalous slip in continuum crystal plasticity formulations. 

PMID- 25062204
TI  - Kinetic signature of fractal-like filament networks formed by orientational
      linear epitaxy.
AB  - We study a broad class of epitaxial assembly of filament networks on lattice
      surfaces. Over time, a scale-free behavior emerges with a 2.5-3 power-law
      exponent in filament length distribution. Partitioning between the power-law and
      exponential behaviors in a network can be used to find the stage and kinetic
      parameters of the assembly process. To analyze real-world networks, we develop a
      computer program that measures the network architecture in experimental images.
      Application to triaxial networks of collagen fibrils shows quantitative agreement
      with our model. Our unifying approach can be used for characterizing and
      controlling the network formation that is observed across biological and
      nonbiological systems. 

PMID- 25062205
TI  - Hydrogen-free amorphous silicon with no tunneling states.
AB  - The ubiquitous low-energy excitations, known as two-level tunneling systems
      (TLSs), are one of the universal phenomena of amorphous solids. Low temperature
      elastic measurements show that e-beam amorphous silicon (a-Si) contains a
      variable density of TLSs which diminishes as the growth temperature reaches 400 
      degrees C. Structural analyses show that these a-Si films become denser and more
      structurally ordered. We conclude that the enhanced surface energetics at a high
      growth temperature improved the amorphous structural network of e-beam a-Si and
      removed TLSs. This work obviates the role hydrogen was previously thought to play
      in removing TLSs in the hydrogenated form of a-Si and suggests it is possible to
      prepare "perfect" amorphous solids with "crystal-like" properties for
      applications. 

PMID- 25062206
TI  - Direct measurement of hydrogen dislocation pipe diffusion in deformed
      polycrystalline Pd using quasielastic neutron scattering.
AB  - The temperature-dependent diffusivity D(T) of hydrogen solute atoms trapped at
      dislocations-dislocation pipe diffusion of hydrogen-in deformed polycrystalline
      PdH(x) (x~10(-3)  [H]/[Pd]) has been quantified with quasielastic neutron
      scattering between 150 and 400 K. We observe diffusion coefficients for trapped
      hydrogen elevated by one to two orders of magnitude above bulk diffusion.
      Arrhenius diffusion behavior has been observed for dislocation pipe diffusion and
      regular bulk diffusion, the latter in well-annealed polycrystalline Pd. For
      regular bulk diffusion of hydrogen in Pd we find D(T)=D(0)exp(-E(a)/kT)=0.005exp(
      0.23  eV/kT)  cm(2)/s, in agreement with the known diffusivity of hydrogen in Pd.
      For hydrogen dislocation pipe diffusion we find D(T)?10(-5)exp(-E(a)/kT) 
      cm(2)/s, where E(a)=0.042 and 0.083 eV for concentrations of 0.52*10(-3) and
      1.13*10(-3)[H]/[Pd], respectively. Ab initio computations provide a physical
      basis for the pipe diffusion pathway and confirm the reduced barrier height.

PMID- 25062207
TI  - Structures of late transition metal monoxides from Jahn-Teller instabilities in
      the rock salt lattice.
AB  - Most late transition metal (LTM) monoxides crystallize in other than a rock salt
      structure, which is so common in the earlier transition metal monoxides. Here we
      present theoretical evidence based on density functional theory that an electron
      phonon coupling involving a single soft mode in the cubic cell is responsible for
      the onset of the experimentally observed structures of the late transition metal
      monoxides. 

PMID- 25062208
TI  - Localization of propagative phonons in a perfectly crystalline solid.
AB  - Perfectly crystalline solids are excellent heat conductors. Prominent
      counterexamples are intermetallic clathrates, guest-host systems with a high
      potential for thermoelectric applications due to their ultralow thermal
      conductivities. Our combined experimental and theoretical investigation of the
      lattice dynamics of a particularly simple binary representative, Ba(8)Si(46),
      identifies the mechanism responsible for the reduction of lattice thermal
      conductivity intrinsic to the perfect crystal structure. Above a critical wave
      vector, the purely harmonic guest-host interaction leads to a drastic transfer of
      spectral weight to the guest atoms, corresponding to a localization of the
      propagative phonons.

PMID- 25062209
TI  - Strong dynamical heterogeneity and universal scaling in driven granular fluids.
AB  - Large-scale simulations of two-dimensional bidisperse granular fluids allow us to
      determine spatial correlations of slow particles via the four-point structure
      factor S(4)(q,t). Both cases, elastic (epsilon=1) and inelastic (epsilon<1)
      collisions, are studied. As the fluid approaches structural arrest, i.e., for
      packing fractions in the range 0.6<=phi<=0.805, scaling is shown to hold:
      S(4)(q,t)/chi(4)(t)=s(qxi(t)). Both the dynamic susceptibility chi(4)(tau(alpha))
      and the dynamic correlation length xi(tau(alpha)) evaluated at the alpha
      relaxation time tau(alpha) can be fitted to a power law divergence at a critical
      packing fraction. The measured xi(tau(alpha)) widely exceeds the largest one
      previously observed for three-dimensional (3d) hard sphere fluids. The number of
      particles in a slow cluster and the correlation length are related by a robust
      power law, chi(4)(tau(alpha))~xi(d-p)(tau(alpha)), with an exponent d-p~1.6. This
      scaling is remarkably independent of epsilon, even though the strength of the
      dynamical heterogeneity at constant volume fraction depends strongly on epsilon.

PMID- 25062210
TI  - (N(2))(6)Ne(7): A high pressure van der Waals insertion compound.
AB  - The binary phase diagram of N(2)-Ne mixtures has been measured at 296 K by visual
      observation and Raman spectroscopy. The topology of the phase diagram points to
      the existence of the stoichiometric compound N(2))(6)Ne(7). Its structure has
      been solved by single-crystal synchrotron x-ray diffraction. The N(2) molecules
      form a guest lattice that hosts the Ne atoms. This insertion compound can be
      viewed as a clathrate with the centers of the N(2) molecules forming distorted
      dodecahedron cages, each enclosing 14 Ne atoms. Remarkably, the N(2))(6)Ne(7)
      compound is somehow the first clathrate organized by the quadrupolar interaction.

PMID- 25062211
TI  - Polar effects on the thermal conductivity of cubic boron nitride under pressure.
AB  - We report the lattice thermal conductivity (kappa) of cubic boron nitride (c-BN)
      under pressure calculated using density functional theory. Pressure was used to
      manipulate the c-BN phonon dispersion and study its effect on thermal
      conductivity. These results were compared to c-BN's mass-equivalent, nonpolar
      counterpart, diamond, in order to isolate the effect of polar bonds on thermal
      conductivity. Unlike diamond, the variation of kappa at room temperature
      (kappa(RT)) with applied pressure in c-BN is nonlinear in the low-pressure regime
      followed by a transition to a linear regime with a distinct change in the slope
      at P>114  GPa. We find that the change in kappa with pressure cannot be described
      with power law expressions commonly used for Earth mantle materials. The
      nonlinearity in the low-pressure regime can be related to the nonlinear change in
      LO-TO gap, group velocities, and specific heat with increasing pressure. In
      addition, we find that, although optical branch contributions to thermal
      conductivity are small (~2% at RT), the rise in kappa(RT) for P>114  GPa is due
      to (1) the decoupling of the longitudinal acoustic branch from the optical
      branches and (2) depopulation of the optical branches. These lead to a sharp
      reduction in acoustic-acoustic-optic (a-a-o) scattering and a discrete change in
      the acoustic phonon mean free paths. This study illustrates the importance of
      optical branches and their interactions with acoustic branches in determining the
      total thermal conductivity of polar materials. This finding is also relevant for
      current research in geologic minerals under pressure and the design of
      thermoelectrics.

PMID- 25062212
TI  - Generalized two-temperature model for coupled phonon-magnon diffusion.
AB  - We generalize the two-temperature model [Sanders and Walton, Phys. Rev. B 15,
      1489 (1977)] for coupled phonon-magnon diffusion to include the effect of the
      concurrent magnetization flow, with a particular emphasis on the thermal
      consequence of the magnon flow driven by a nonuniform magnetic field. Working
      within the framework of the Boltzmann transport equation, we derive the
      constitutive equations for coupled phonon-magnon transport driven by gradients of
      both temperature and external magnetic fields, and the corresponding conservation
      laws. Our equations reduce to the original Sanders-Walton two-temperature model
      under a uniform external field, but predict a new magnon cooling effect driven by
      a nonuniform magnetic field in a homogeneous single-domain ferromagnet. We
      estimate the magnitude of the cooling effect in an yttrium iron garnet, and show
      it is within current experimental reach. With properly optimized materials, the
      predicted cooling effect can potentially supplement the conventional
      magnetocaloric effect in cryogenic applications in the future.

PMID- 25062213
TI  - Substrate curvature gradient drives rapid droplet motion.
AB  - Making small liquid droplets move spontaneously on solid surfaces is a key
      challenge in lab-on-chip and heat exchanger technologies. Here, we report that a
      substrate curvature gradient can accelerate micro- and nanodroplets to high
      speeds on both hydrophilic and hydrophobic substrates. Experiments for microscale
      water droplets on tapered surfaces show a maximum speed of 0.42  m/s, 2 orders of
      magnitude higher than with a wettability gradient. We show that the total free
      energy and driving force exerted on a droplet are determined by the substrate
      curvature and substrate curvature gradient, respectively. Using molecular
      dynamics simulations, we predict nanoscale droplets moving spontaneously at over
      100  m/s on tapered surfaces. 

PMID- 25062214
TI  - Coherent structural dynamics of a prototypical charge-density-wave-to-metal
      transition.
AB  - Using femtosecond time-resolved x-ray diffraction, we directly monitor the
      coherent lattice dynamics through an ultrafast charge-density-wave-to-metal
      transition in the prototypical Peierls system K(0.3)MoO(3) over a wide range of
      relevant excitation fluences. While in the low fluence regime we directly follow
      the structural dynamics associated with the collective amplitude mode; for
      fluences above the melting threshold of the electronic density modulation we
      observe a transient recovery of the periodic lattice distortion. We can describe
      these structural dynamics as a motion along the coordinate of the Peierls
      distortion triggered by the prompt collapse of electronic order after
      photoexcitation. The results indicate that the dynamics of a structural symmetry
      breaking transition are determined by a high-symmetry excited state potential
      energy surface distinct from that of the initial low-temperature state.

PMID- 25062215
TI  - Fermi-edge transmission resonance in graphene driven by a single Coulomb
      impurity.
AB  - The interaction between the Fermi sea of conduction electrons and a nonadiabatic
      attractive impurity potential can lead to a power-law divergence in the tunneling
      probability of charge through the impurity. The resulting effect, known as the
      Fermi edge singularity (FES), constitutes one of the most fundamental many-body
      phenomena in quantum solid state physics. Here we report the first observation of
      FES for Dirac fermions in graphene driven by isolated Coulomb impurities in the
      conduction channel. In high-mobility graphene devices on hexagonal boron nitride
      substrates, the FES manifests in abrupt changes in conductance with a large
      magnitude ~e(2)/h at resonance, indicating total many-body screening of a local
      Coulomb impurity with fluctuating charge occupancy. Furthermore, we exploit the
      extreme sensitivity of graphene to individual Coulomb impurities and demonstrate
      a new defect-spectroscopy tool to investigate strongly correlated phases in
      graphene in the quantum Hall regime.

PMID- 25062216
TI  - Quantum transport of disordered Weyl semimetals at the nodal point.
AB  - Weyl semimetals are paradigmatic topological gapless phases in three dimensions.
      We here address the effect of disorder on charge transport in Weyl semimetals.
      For a single Weyl node with energy at the degeneracy point and without
      interactions, theory predicts the existence of a critical disorder strength
      beyond which the density of states takes on a nonzero value. Predictions for the
      conductivity are divergent, however. In this work, we present a numerical study
      of transport properties for a disordered Weyl cone at zero energy. For weak
      disorder, our results are consistent with a renormalization group flow towards an
      attractive pseudoballistic fixed point with zero conductivity and a scale
      independent conductance; for stronger disorder, diffusive behavior is reached. We
      identify the Fano factor as a signature that discriminates between these two
      regimes. 

PMID- 25062217
TI  - Emergence of decoupled surface transport channels in bulk insulating Bi(2)Se(3)
      thin films.
AB  - In ideal topological insulator (TI) films the bulk state, which is supposed to be
      insulating, should not provide any electric coupling between the two metallic
      surfaces. However, transport studies on existing TI films show that the
      topological states on opposite surfaces are electrically tied to each other at
      thicknesses far greater than the direct coupling limit where the surface wave
      functions overlap. Here, we show that as the conducting bulk channels are
      suppressed, the parasitic coupling effect diminishes, and the decoupled surface
      channels emerge as expected for ideal TIs. In Bi(2)Se(3) thin films with fully
      suppressed bulk states, the two surfaces, which are directly coupled below ~10 
      QL, become gradually isolated with increasing thickness and are completely
      decoupled beyond ~20  QL. On such a platform, it is now feasible to implement
      transport devices whose functionality relies on accessing the individual surface
      layers without any deleterious coupling effects.

PMID- 25062218
TI  - Electron supercollimation in graphene and Dirac fermion materials using one
      dimensional disorder potentials.
AB  - Electron supercollimation, in which a wave packet is guided to move undistorted
      along a selected direction, is a highly desirable property that has yet to be
      realized experimentally. Disorder in general is expected to inhibit
      supercollimation. Here we report a counterintuitive phenomenon of electron
      supercollimation by disorder in graphene and related Dirac fermion materials. We
      show that one can use one-dimensional disorder potentials to control electron
      wave packet transport. This is distinct from known systems where an electron wave
      packet would be further spread by disorder and hindered in the potential
      fluctuating direction. The predicted phenomenon has significant implications in
      the understanding and applications of electron transport in Dirac fermion
      materials. 

PMID- 25062219
TI  - Tightly bound excitons in monolayer WSe(2).
AB  - Exciton binding energy and excited states in monolayers of tungsten diselenide
      (WSe(2)) are investigated using the combined linear absorption and two-photon
      photoluminescence excitation spectroscopy. The exciton binding energy is
      determined to be 0.37 eV, which is about an order of magnitude larger than that
      in III-V semiconductor quantum wells and renders the exciton excited states
      observable even at room temperature. The exciton excitation spectrum with both
      experimentally determined one- and two-photon active states is distinct from the
      simple two-dimensional (2D) hydrogenic model. This result reveals significantly
      reduced and nonlocal dielectric screening of Coulomb interactions in 2D
      semiconductors. The observed large exciton binding energy will also have a
      significant impact on next-generation photonics and optoelectronics applications
      based on 2D atomic crystals.

PMID- 25062220
TI  - Images of edge current in InAs/GaSb quantum wells.
AB  - Quantum spin Hall devices with edges much longer than several microns do not
      display ballistic transport; that is, their measured conductances are much less
      than e(2)/h per edge. We imaged edge currents in InAs/GaSb quantum wells with
      long edges and determined an effective edge resistance. Surprisingly, although
      the effective edge resistance is much greater than h/e(2), it is independent of
      temperature up to 30 K within experimental resolution. Known candidate scattering
      mechanisms do not explain our observation of an effective edge resistance that is
      large yet temperature independent.

PMID- 25062221
TI  - Lamb-shift enhancement and detection in strongly driven superconducting circuits.
AB  - It is shown that strong driving of a quantum system substantially enhances the
      Lamb shift induced by broadband reservoirs, which are typical for solid-state
      devices. By varying drive parameters the impact of environmental vacuum
      fluctuations with continuous spectral distribution onto system observables can be
      tuned in a distinctive way. This provides experimentally feasible measurement
      schemes for the Lamb shift in superconducting circuits based on Cooper pair
      boxes, where it can be detected either in shifted dressed transition frequencies
      or in pumped charge currents. 

PMID- 25062222
TI  - Model of the electronic structure of electron-doped iron-based superconductors:
      evidence for enhanced spin fluctuations by diagonal electron hopping.
AB  - We present a theoretical understanding of the superconducting phase diagram of
      the electron-doped iron pnictides. We show that, besides the Fermi surface
      nesting, a peculiar motion of electrons, where the next nearest neighbor
      (diagonal) hoppings between iron sites dominate over the nearest neighbor ones,
      plays an important role in the enhancement of the spin fluctuation and thus
      superconductivity. In the highest T(c) materials, the crossover between the Fermi
      surface nesting and this "prioritized diagonal motion" regime occurs smoothly
      with doping, while in relatively low T(c) materials, the two regimes are
      separated and therefore results in a double dome T(c) phase diagram.

PMID- 25062223
TI  - Plaquette ordered phase and quantum phase diagram in the spin-1/2 J(1)-J(2)
      square Heisenberg model.
AB  - We study the spin-1/2 Heisenberg model on the square lattice with first- and
      second-neighbor antiferromagnetic interactions J(1) and J(2), which possesses a
      nonmagnetic region that has been debated for many years and might realize the
      interesting Z(2) spin liquid. We use the density matrix renormalization group
      approach with explicit implementation of SU(2) spin rotation symmetry and study
      the model accurately on open cylinders with different boundary conditions. With
      increasing J(2), we find a Neel phase and a plaquette valence-bond (PVB) phase
      with a finite spin gap. From the finite-size scaling of the magnetic order
      parameter, we estimate that the Neel order vanishes at J(2)/J(1)?0.44. For
      0.5<J(2)/J(1)<0.61, we find dimer correlations and PVB textures whose decay
      lengths grow strongly with increasing system width, consistent with a long-range
      PVB order in the two-dimensional limit. The dimer-dimer correlations reveal the s
      wave character of the PVB order. For 0.44<J(2)/J(1)<0.5, spin order, dimer order,
      and spin gap are small on finite-size systems, which is consistent with a near
      critical behavior. The critical exponents obtained from the finite-size spin and
      dimer correlations could be compatible with the deconfined criticality in this
      small region. We compare and contrast our results with earlier numerical studies.

PMID- 25062224
TI  - Berry-phase-induced dimerization in one-dimensional quadrupolar systems.
AB  - We investigate the effect of the Berry phase on quadrupoles that occur, for
      example, in the low-energy description of spin models. Specifically, we study
      here the one-dimensional bilinear-biquadratic spin-one model. An open question
      for many years about this model is whether it has a nondimerized fluctuating
      nematic phase. The dimerization has recently been proposed to be related to Berry
      phases of the quantum fluctuations. We use an effective low-energy description to
      calculate the scaling of the dimerization according to this theory and then
      verify the predictions using large scale density-matrix renormalization group
      simulations, giving good evidence that the state is dimerized all the way up to
      its transition into the ferromagnetic phase. We furthermore discuss the multiplet
      structure found in the entanglement spectrum of the ground state wave functions. 

PMID- 25062225
TI  - Magnetic edge anisotropy in graphenelike honeycomb crystals.
AB  - The independent predictions of edge ferromagnetism and the quantum spin Hall
      phase in graphene have inspired the quest of other two-dimensional honeycomb
      systems, such as silicene, germanene, stanene, iridates, and organometallic
      lattices, as well as artificial superlattices, all of them with electronic
      properties analogous to those of graphene, but a larger spin-orbit coupling.
      Here, we study the interplay of ferromagnetic order and spin-orbit interactions
      at the zigzag edges of these graphenelike systems. We find an in-plane magnetic
      anisotropy that opens a gap in the otherwise conducting edge channels that should
      result in large changes of electronic properties upon rotation of the
      magnetization. 

PMID- 25062226
TI  - Order-by-disorder and quantum Coulomb phase in quantum square ice.
AB  - We show that quantum square ice-namely, the two-dimensional version of proton or
      spin ice with tunable quantum tunneling of the electric or magnetic dipole moment
      exhibits a quantum spin-liquid phase supporting fractionalized spinons. This
      phase corresponds to a thermally induced, deconfined quantum Coulomb phase of a
      two-dimensional lattice gauge theory. It emerges at finite, yet exceedingly low
      temperatures from the melting of two distinct order-by-disorder phases appearing
      in the ground state: a plaquette valence-bond solid for low tunneling; and a
      canted Neel state for stronger tunneling. The latter phases appear via the highly
      nonlinear effect of quantum fluctuations within the degenerate manifold of ice
      rule states, and they can be identified as the two competing ground states of a
      discrete lattice gauge theory (quantum link model) emerging as the effective
      Hamiltonian of the system within degenerate perturbation theory. 

PMID- 25062227
TI  - Pinning-dependent field-driven domain wall dynamics and thermal scaling in an
      ultrathin Pt/Co/Pt magnetic film.
AB  - Magnetic-field-driven domain wall motion in an ultrathin Pt/Co(0.45  nm)/Pt
      ferromagnetic film with perpendicular anisotropy is studied over a wide
      temperature range. Three different pinning dependent dynamical regimes are
      clearly identified: the creep, the thermally assisted flux flow, and the
      depinning, as well as their corresponding crossovers. The wall elastic energy and
      microscopic parameters characterizing the pinning are determined. Both the
      extracted thermal rounding exponent at the depinning transition, psi=0.15, and
      the Larkin length crossover exponent, phi=0.24, fit well with the numerical
      predictions. 

PMID- 25062228
TI  - Optical feedback-enhanced photon entanglement from a biexciton cascade.
AB  - In a solid-state platform for quantum information science, the biexciton cascade
      is an important source of entangled photons. However, the entanglement is usually
      reduced considerably by the fine-structure splitting of the exciton levels. We
      show how to counteract this loss of entanglement by applying optical feedback.
      Substantial control and enhancement of photon entanglement can be achieved by
      coherently feeding back a part of the emitted signal, e.g., by a mirror, and by
      tuning the feedback phase and delay time. We present full quantum-mechanical
      calculations, which include the external photon mode continuum, and discuss the
      mechanisms leading to the above effects. 

PMID- 25062229
TI  - Observation of standing waves of electron-hole sound in a photoexcited
      semiconductor.
AB  - Three-dimensional multicomponent plasmas composed of species with very different
      masses support a new branch of charge-density fluctuations known as acoustic
      plasmons. Here, we report on an ultrafast optical method to generate and probe
      coherent states of acoustic plasmons in a slab of GaAs, which relies on strong
      photoexcitation to create a large population of light electrons and heavy holes.
      Consistent with the random-phase-approximation theory, the data reveal standing
      plasma waves confined to these slabs, similar to those of conventional sound but
      with associated velocities that are significantly larger. 

PMID- 25062230
TI  - Resonant interactions between a Mollow triplet sideband and a strongly coupled
      cavity.
AB  - We demonstrate resonant coupling of a Mollow triplet sideband to an optical
      cavity in the strong coupling regime. We show that, in this regime, the resonant
      sideband is strongly enhanced relative to the detuned sideband. Furthermore, the
      linewidth of the Mollow sidebands exhibits a highly nonlinear pump power
      dependence when tuned across the cavity resonance due to strong resonant
      interactions with the cavity mode. We compare our results to calculations using
      the effective phonon master equation and show that the nonlinear linewidth
      behavior is caused by strong coherent interaction with the cavity mode that
      exists only when the Mollow sideband is near cavity resonance. 

PMID- 25062231
TI  - Graphene optomechanics realized at microwave frequencies.
AB  - Cavity optomechanics has served as a platform for studying the interaction
      between light and micromechanical motion via radiation pressure. Here we observe
      such phenomena with a graphene mechanical resonator coupled to an electromagnetic
      mode. We measure thermal motion and backaction cooling in a bilayer graphene
      resonator coupled to a microwave on-chip cavity. We detect the lowest flexural
      mode at 24 MHz down to 60 mK, corresponding to 50+/-6 mechanical quanta, which
      represents a phonon occupation that is nearly 3 orders of magnitude lower than
      that which has been recorded to date with graphene resonators. 

PMID- 25062232
TI  - Nonlinear electromagnetic response of a uniform electron gas.
AB  - The linear electromagnetic response of a uniform electron gas to a longitudinal
      electric field is determined, within the self-consistent-field theory, by the
      linear polarizability and the Lindhard dielectric function. Using the same
      approach, we derive analytical expressions for the second- and third-order
      nonlinear polarizabilities of the three-, two-, and one-dimensional homogeneous
      electron gases with the parabolic electron energy dispersion. The results are
      valid both for degenerate (Fermi) and nondegenerate (Boltzmann) electron gases. A
      resonant enhancement of the second- and third-harmonics generation due to a
      combination of the single-particle and collective (plasma) resonances is
      predicted. 

PMID- 25062233
TI  - Observation of the spin Peltier effect for magnetic insulators.
AB  - We report the observation of the spin Peltier effect (SPE) in the ferrimagnetic
      insulator yttrium iron garnet (YIG), i.e., a heat current generated by a spin
      current flowing through a platinum (Pt)|YIG interface. The effect can be
      explained by the spin transfer torque that transforms the spin current in the Pt
      into a magnon current in the YIG. Via magnon-phonon interactions the magnetic
      fluctuations modulate the phonon temperature that is detected by a thermopile
      close to the interface. By finite-element modeling we verify the reciprocity
      between the spin Peltier and spin Seebeck effect. The observed strong coupling
      between thermal magnons and phonons in YIG is attractive for nanoscale cooling
      techniques. 

PMID- 25062234
TI  - Probing surface noise with depth-calibrated spins in diamond.
AB  - Sensitive nanoscale magnetic resonance imaging of target spins using nitrogen
      vacancy (NV) centers in diamond requires a quantitative understanding of dominant
      noise at the surface. We probe this noise by applying dynamical decoupling to
      shallow NVs at calibrated depths. Results support a model of NV dephasing by a
      surface bath of electronic spins having a correlation rate of 200 kHz, much
      faster than that of the bulk N spin bath. Our method of combining nitrogen delta
      doping growth and nanoscale depth imaging paves a way for studying spin noise
      present in diverse material surfaces. 

PMID- 25062235
TI  - Experimental realization of a three-dimensional Dirac semimetal.
AB  - We report the direct observation of the three-dimensional (3D) Dirac semimetal
      phase in cadmium arsenide (Cd(3)As(2)) by means of angle-resolved photoemission
      spectroscopy. We identify two momentum regions where electronic states that
      strongly disperse in all directions form narrow conelike structures, and thus
      prove the existence of the long sought 3D Dirac points. This electronic structure
      naturally explains why Cd(3)As(2) has one of the highest known bulk electron
      mobilities. This realization of a 3D Dirac semimetal in Cd(3)As(2) not only opens
      a direct path to a wide spectrum of applications, but also offers a robust
      platform for engineering topologically nontrivial phases including Weyl
      semimetals and quantum spin Hall systems.

PMID- 25062236
TI  - Direct experimental observation of a new mechanism for sputtering of solids by a
      large polyatomic projectile: velocity-correlated cluster emission.
AB  - We have measured kinetic energy distributions of Ta(n)C(n)(+) (n=1-10) and
      Ag(n)(+) (n=1-9) cluster ions sputtered off Ta and Ag targets, following impact
      of C(60)(-) at 14 keV kinetic energy. A gradual increase of the most probable
      kinetic energies with increased size of the emitted cluster was observed (nearly
      the same velocity for all n values). This behavior is in sharp contrast to that
      reported for cluster emission induced by the impact of a monoatomic projectile.
      Our observation is in good agreement with a mechanism based on the new concept of
      a superhot moving precursor as the source of the emitted clusters.

PMID- 25062237
TI  - Knotted defects in nematic liquid crystals.
AB  - We show that the number of distinct topological states associated with a given
      knotted defect, L, in a nematic liquid crystal is equal to the determinant of the
      link L. We give an interpretation of these states, demonstrate how they may be
      identified in experiments, and describe the consequences for material behavior
      and interactions between multiple knots. We show that stable knots can be created
      in a bulk cholesteric and illustrate the topology by classifying a simulated Hopf
      link. In addition, we give a topological heuristic for the resolution of strand
      crossings in defect coarsening processes which allows us to distinguish
      topological classes of a given link and to make predictions about defect
      crossings in nematic liquid crystals. 

PMID- 25062238
TI  - Universality in stochastic exponential growth.
AB  - Recent imaging data for single bacterial cells reveal that their mean sizes grow
      exponentially in time and that their size distributions collapse to a single
      curve when rescaled by their means. An analogous result holds for the division
      time distributions. A model is needed to delineate the minimal requirements for
      these scaling behaviors. We formulate a microscopic theory of stochastic
      exponential growth as a Master Equation that accounts for these observations, in
      contrast to existing quantitative models of stochastic exponential growth (e.g.,
      the Black-Scholes equation or geometric Brownian motion). Our model, the
      stochastic Hinshelwood cycle (SHC), is an autocatalytic reaction cycle in which
      each molecular species catalyzes the production of the next. By finding exact
      analytical solutions to the SHC and the corresponding first passage time problem,
      we uncover universal signatures of fluctuations in exponential growth and
      division. The model makes minimal assumptions, and we describe how more complex
      reaction networks can reduce to such a cycle. We thus expect similar scalings to
      be discovered in stochastic processes resulting in exponential growth that appear
      in diverse contexts such as cosmology, finance, technology, and population
      growth. 

PMID- 25062239
TI  - Stress reorganization and response in active solids.
AB  - We present a microscopic model of a disordered viscoelastic active solid, i.e.,
      an active material whose long time behavior is elastic as opposed to viscous. It
      is composed of filaments, passive cross-links, and molecular motors powered by
      stored chemical energy, e.g., actomyosin powered by adenosine triphosphate. Our
      model allows us to study the collective behavior of contractile active elements
      and how their interaction with each other and the passive elastic elements
      determines the macroscopic mechanical properties of the active material. As a
      result of the (un)binding dynamics of the active elements, we find that this
      system provides a highly responsive material with a dynamic mechanical response
      strongly dependent on the amount of deformation. 

PMID- 25062240
TI  - Swim pressure: stress generation in active matter.
AB  - We discover a new contribution to the pressure (or stress) exerted by a
      suspension of self-propelled bodies. Through their self-motion, all active matter
      systems generate a unique swim pressure that is entirely athermal in origin. The
      origin of the swim pressure is based upon the notion that an active body would
      swim away in space unless confined by boundaries-this confinement pressure is
      precisely the swim pressure. Here we give the micromechanical basis for the swim
      stress and use this new perspective to study self-assembly and phase separation
      in active soft matter. The swim pressure gives rise to a nonequilibrium equation
      of state for active matter with pressure-volume phase diagrams that resemble a
      van der Waals loop from equilibrium gas-liquid coexistence. Theoretical
      predictions are corroborated by Brownian dynamics simulations. Our new swim
      stress perspective can help analyze and exploit a wide class of active soft
      matter, from swimming bacteria to catalytic nanobots to molecular motors that
      activate the cellular cytoskeleton. 

PMID- 25062241
TI  - Imbibition kinetics of spherical colloidal aggregates.
AB  - The imbibition kinetics of a millimeter-sized aggregate of 300 nm diameter
      colloidal particles by a wetting pure solvent is studied. Three successive
      regimes are observed. First, the imbibition proceeds by compressing the air
      inside the aggregate. Next, the solvent stops when the pressure of the compressed
      air is equal to the excess of capillary pressure at the meniscus of the wetting
      solvent in the porous aggregate. The interface is pinned and the aggregate slowly
      degases up to the point where the pressure of the entrapped air stops decreasing
      and is controlled by the capillary pressure. Finally, the imbibition starts again
      at a constant excess of pressure, smaller than the capillary pressure but larger
      than the one of the atmosphere. This last stage leads to the complete
      infiltration of the aggregate. 

PMID- 25062242
TI  - Zero-mode waveguide detection of flow-driven DNA translocation through nanopores.
AB  - We directly measure the flow-driven injection of DNA through nanopores at the
      level of single molecule and single pore using a modified zero-mode waveguide
      method. We observe a flow threshold independent of the pore radius, the DNA
      concentration, and length. We demonstrate that the flow injection of DNA in
      nanopores is controlled by an energy barrier as proposed in the de Gennes
      Brochard suction model. Finally, we show that the height of the energy barrier is
      modulated by functionalizing the nanopores. 

PMID- 25062243
TI  - Calculated rates of diffusion-limited reactions in a three-dimensional network of
      connected compartments: application to porous catalysts and biological systems.
AB  - We describe the diffusion limit for reaction rates in a three-dimensional system
      of connected compartments. This model exhibits the length-scale dependent
      diffusion that can be observed in many heterogeneous environments, such as porous
      catalysts and biological environments. We obtain a simple analytical expression
      for the diffusion limit applicable to any scale of the compartment confinement.
      This diffusion limit exceeds the classic Smoluchowski diffusion limit that was
      derived for homogeneous environments but is often applied to biological reactions
      in heterogeneous environments. We expect our new diffusion limit to provide a
      more appropriate upper bound on reaction rates in biological systems, porous
      structures, and other heterogeneous environments where obstacles create local
      confinement. 

PMID- 25062244
TI  - Assessing carbon-based anodes for lithium-ion batteries: a universal description
      of charge-transfer binding.
AB  - Many key performance characteristics of carbon-based lithium-ion battery anodes
      are largely determined by the strength of binding between lithium (Li) and sp(2)
      carbon (C), which can vary significantly with subtle changes in substrate
      structure, chemistry, and morphology. Here, we use density functional theory
      calculations to investigate the interactions of Li with a wide variety of sp(2) C
      substrates, including pristine, defective, and strained graphene, planar C
      clusters, nanotubes, C edges, and multilayer stacks. In almost all cases, we find
      a universal linear relation between the Li-C binding energy and the work required
      to fill previously unoccupied electronic states within the substrate. This
      suggests that Li capacity is predominantly determined by two key factors-namely,
      intrinsic quantum capacitance limitations and the absolute placement of the Fermi
      level. This simple descriptor allows for straightforward prediction of the Li-C
      binding energy and related battery characteristics in candidate C materials based
      solely on the substrate electronic structure. It further suggests specific
      guidelines for designing more effective C-based anodes. The method should be
      broadly applicable to charge-transfer adsorption on planar substrates, and
      provides a phenomenological connection to established principles in
      supercapacitor and catalyst design.

PMID- 25062245
TI  - Comment on "Electromagnetic vortex fields, spin, and spin-orbit interactions in
      electron vortices".

PMID- 25062246
TI  - Comment on "Tuning the magnetic dimensionality by charge ordering in the
      molecular TMTTF salts".

PMID- 25062247
TI  - Seo et al. reply:.

PMID- 25062248
TI  - Comment on "Circular motion of asymmetric self-propelling particles".

PMID- 25062249
TI  - Kummel et al. reply:.

PMID- 25062250
TI  - Excitability of the motor cortex in de novo patients with celiac disease.
AB  - INTRODUCTION: Celiac disease (CD) may initially present as a neurological
      disorder or may be complicated by neurological changes. To date,
      neurophysiological studies aiming to an objective evaluation of the potential
      central nervous system involvement in CD are lacking. OBJECTIVE: To assess the
      profile of cortical excitability to Transcranial Magnetic Stimulation (TMS) in a
      group of de novo CD patients. MATERIALS AND METHODS: Twenty CD patients underwent
      a screening for cognitive and neuropsychiatric symptoms by means of the Mini
      Mental State Examination and the Structured Clinical Interview for DSM-IV Axis I
      Disorders, respectively. Instrumental exams, including electroencephalography and
      brain computed tomography, were also performed. Cortico-spinal excitability was
      assessed by means of single and paired-pulse TMS using the first dorsal
      interosseus muscle of the dominant hand. TMS measures consisted of resting motor
      threshold, motor evoked potentials, cortical silent period (CSP), intracortical
      inhibition (ICI) and facilitation (ICF). None of the CD was on gluten-free diet.
      A group of 20 age-matched healthy controls was used for comparisons. RESULTS: CD
      showed a significantly shorter CSP (78.0 vs 125.0 ms, p<0.025), a reduced ICI
      (0.3 vs 0.2, p<0.045) and an enhanced ICF (1.1 vs 0.7, p<0.042) compared to
      controls. A dysthymic disorder was identified in five patients. The effect size
      between dysthymic and non-dysthymic CD patients indicated a low probability of
      interference with the CSP (Cohen's d -0.414), ICI (-0.278) and ICF (-0.292)
      measurements. CONCLUSION: A pattern of cortical excitability characterized by
      "disinhibition" and "hyperfacilitation" was found in CD patients. Immune system
      dysregulation might play a central role in triggering changes of the motor cortex
      excitability.

PMID- 25062251
TI  - Association between the intrinsically disordered protein PEX19 and PEX3.
AB  - In peroxisomes, peroxins (PEXs) 3 and 19 are the principal protein components of
      the machinery required for early peroxisomal biogenesis. For further insight into
      the interaction of PEX3 and PEX19, we used hydrogen exchange mass spectrometry to
      monitor conformational changes during complex formation between PEX3 and PEX19 in
      vitro. Our data showed that PEX19 remained highly flexible during interaction
      with PEX3. However, we could detect three changes, one each in the N-and C
      terminus along with a small stretch in the middle of PEX19 (F64-L74) which became
      shielded from hydrogen exchange when interacting with PEX3. PEX3 became more
      protected from hydrogen exchange in the binding groove for PEX19 with only small
      changes elsewhere. Most likely the N-terminus of PEX19 initiates the binding to
      PEX3, and then subtle conformational changes in PEX3 affect the surface of the
      PEX3 molecule. PEX19 in turn, is stabilized by folding of a short helix and its C
      terminal folding core permitting PEX19 to bind to PEX3 with higher affinity than
      just the N-terminal interaction allows. Thus within the cell, PEX3 is stabilized
      by PEX19 preventing PEX3 aggregation. 

PMID- 25062253
TI  - Proteasome inhibitors activate autophagy involving inhibition of PI3K-Akt-mTOR
      pathway as an anti-oxidation defense in human RPE cells.
AB  - The two major intracellular protein degradation systems, the ubiquitin-proteasome
      system (UPS) and autophagy, work collaboratively in many biological processes
      including development, apoptosis, aging, and countering oxidative injuries. We
      report here that, in human retinal pigment epithelial cells (RPE), ARPE-19 cells,
      proteasome inhibitors, clasto-lactacystinbeta-lactone (LA) or epoxomicin (Epo),
      at non-lethal doses, increased the protein levels of autophagy-specific genes
      Atg5 and Atg7 and enhanced the conversion of microtubule-associated protein light
      chain (LC3) from LC3-I to its lipidative form, LC3-II, which was enhanced by co
      addition of the saturated concentration of Bafilomycin A1 (Baf). Detection of co
      localization for LC3 staining and labeled-lysosome further confirmed autophagic
      flux induced by LA or Epo. LA or Epo reduced the phosphorylation of the protein
      kinase B (Akt), a downstream target of phosphatidylinositol-3-kinases (PI3K), and
      mammalian target of rapamycin (mTOR) in ARPE-19 cells; by contrast, the induced
      changes of autophagy substrate, p62, showed biphasic pattern. The autophagy
      inhibitor, Baf, attenuated the reduction in oxidative injury conferred by
      treatment with low doses of LA and Epo in ARPE-19 cells exposed to menadione
      (VK3) or 4-hydroxynonenal (4-HNE). Knockdown of Atg7 with siRNA in ARPE-19 cells
      reduced the protective effects of LA or Epo against VK3. Overall, our results
      suggest that treatment with low levels of proteasome inhibitors confers
      resistance to oxidative injury by a pathway involving inhibition of the PI3K-Akt
      mTOR pathway and activation of autophagy. 

PMID- 25062254
TI  - Geographic distribution of MERS coronavirus among dromedary camels, Africa.
AB  - We found serologic evidence for the circulation of Middle East respiratory
      syndrome coronavirus among dromedary camels in Nigeria, Tunisia, and Ethiopia.
      Circulation of the virus among dromedaries across broad areas of Africa may
      indicate that this disease is currently underdiagnosed in humans outside the
      Arabian Peninsula. 

PMID- 25062255
TI  - JAGuaR: junction alignments to genome for RNA-seq reads.
AB  - JAGuaR is an alignment protocol for RNA-seq reads that uses an extended reference
      to increase alignment sensitivity. It uses BWA to align reads to the genome and
      reference transcript models (including annotated exon-exon junctions)
      specifically allowing for the possibility of a single read spanning multiple
      exons. Reads aligned to the transcript models are then re-mapped on to genomic
      coordinates, transforming alignments that span multiple exons into large-gapped
      alignments on the genome. While JAGuaR does not detect novel junctions, we
      demonstrate how JAGuaR generates fast and accurate transcriptome alignments,
      which allows for both sensitive and specific SNV calling. 

PMID- 25062256
TI  - Identification of copy number variants through whole-exome sequencing in
      autosomal recessive nonsyndromic hearing loss.
AB  - Genetic variants account for more than half of the cases with congenital or
      prelingual onset hearing loss. Autosomal recessive nonsyndromic hearing loss
      (ARNSHL) is the most common subgroup. Whole-exome sequencing (WES) has been shown
      to be effective detecting deafness-causing single-nucleotide variants (SNVs) and
      insertion/deletions (INDELs). After analyzing the WES data for causative SNVs or
      INDELs involving previously reported deafness genes in 78 families with ARNSHL,
      we searched for copy number variants (CNVs) through two different tools in 24
      families that remained unresolved. We detected large homozygous deletions in STRC
      and OTOA in single families. Thus, causative CNVs in known deafness genes explain
      2 out of 78 (2.6%) families in our sample set. We conclude that CNVs can be
      reliably detected through WES and should be the part of pipelines used to clarify
      genetic basis of hearing loss. 

PMID- 25062257
TI  - Two decades of history of laparoscopic pediatric inguinal hernia repair.

PMID- 25062258
TI  - Immunolabeling for p16, WT1, and Fli-1 in the assignment of growth phase for
      cutaneous melanomas.
AB  - Distinction between radial growth phase (RGP) and vertical growth phase (VGP) in
      cutaneous melanomas is prognostically significant. Despite established
      morphological criteria, molecular markers to separate RGP and VGP have not been
      well established. The goal of this study was to investigate associations of p16,
      WT1, and Fli-1 with RGP-to-VGP progression, by immunohistochemistry. The p16 is a
      tumor suppressor, whereas WT1 and Fli-1 are transcriptional activators. The
      authors hypothesized that entry into VGP would be associated with decreased p16
      and increased WT1 and Fli-1. Paraffin sections from 18 RGP and 15 VGP melanomas
      were immunostained with well-characterized antibodies to p16, WT1, and Fli-1.
      Melanoma growth phases were determined using precodified morphological
      attributes. In RGP melanomas, p16 was expressed in 15 of 18 (83%), WT1 in 17 of
      17 (100%), and Fli-1 at least focally in 6 of 18 (33%). The deep dermal component
      of VGP melanomas stained positively for Fli-1 in 9 of 14 (64%), strongly for WT1
      in 10 of 14 (71%), and strongly for p16 in only 2 of 15 (13%). Observed patterns
      of WT1 immunopositivity did not support the authors' hypothesis; it is not likely
      to be a good indicator of VGP. On the other hand, Fli-1 staining trended toward
      more positive deep tumor compartment staining and p16 to weaker staining in the
      deep compartment. At present, application of histological criteria remains the
      best method for assignment of growth phase in melanomas; however, p16 and
      possibly Fli-1 immunostains may serve as useful adjuncts in morphologically
      indeterminate cases.

PMID- 25062259
TI  - Primary cutaneous adenoid cystic carcinoma of the scalp with p16 expression: a
      case report and review of the literature.
AB  - INTRODUCTION: Adenoid cystic carcinoma (ACC) is a rare carcinoma that typically
      arises in salivary glands but can also occur in other sites including skin.
      Primary salivary ACC is a locally aggressive tumor characterized by local
      recurrence and late metastasis. Primary cutaneous ACC is found predominately on
      the scalp and is more indolent than salivary ACC; and, despite a high incidence
      of local recurrence, metastases are exceedingly rare. METHODS: A 62-year-old
      white male presented with a 6-mm mobile, blue-tinted nodule on the left mid scalp
      unchanged for several years. RESULTS: The histopathological findings of an
      excisional biopsy were diagnostic for a primary cutaneous ACC.
      Immunohistochemistry demonstrated focal positivity for p16. CONCLUSIONS: Primary
      cutaneous ACC is a rare malignancy that should be considered in the differential
      diagnosis of adnexal neoplasms and, when occurring on the head and neck, must be
      distinguished from cutaneous involvement by salivary ACC. The majority of
      reported salivary ACC with p16 protein expression were not positive for high-risk
      human papilloma virus by in situ hybridization. Immunostaining for p16 has
      previously been reported in salivary gland ACC. This is the first report in the
      English literature of p16 immunoexpression in primary cutaneous ACC.

PMID- 25062260
TI  - An unusual case of porocarcinoma arising on the scalp of a 22-year-old woman.
AB  - Porocarcinoma is a rare malignant neoplasm that arises from the intraepidermal
      ductal portion of the eccrine sweat glands. This neoplasm most often presents in
      elderly individuals on the lower extremities. We present an unusual case of
      porocarcinoma arising on the scalp of a young patient. To the best of our
      knowledge, there have been fewer than 20 cases of porocarcinomas arising at this
      site reported in the literature.

PMID- 25062261
TI  - Noninfectious cutaneous granulomas in primary immunodeficiency disorders: report
      from a national registry.
AB  - : The association of noninfectious cutaneous granulomas with primary
      immunodeficiency disorders (PIDs) is a rare but well-recognized phenomenon. With
      the recent advent of new classification and broadening of the list of PIDs, there
      is now ever-growing number of PIDs having being reported with noninfectious
      cutaneous granulomas or granulomatous tissue reactions. The authors observed 4
      patients with cutaneous granulomas associated with PIDs that constitute 2% of
      total PIDs registered with them. In this report, the authors describe these 4
      patients with cutaneous granulomas/granulomatous skin reactions associated one
      each with common variable immunodeficiency, Omenn syndrome, combined
      immunodeficiency, and Blau syndrome (BS), and briefly review the literature on
      various clinicopathological patterns of cutaneous granulomas with possible
      underlying pathogenetic mechanisms responsible for such tissue reactions in
      patients with PID. 

PMID- 25062262
TI  - Isolated Cutaneous Leishmaniasis by Leishmania donovani in a Soldier Returning
      From Afghanistan.

PMID- 25062263
TI  - Metastatic melanoma in association with a giant congenital melanocytic nevus in
      an adult: controversial CGH findings.
AB  - Giant congenital melanocytic nevi (GCMNs) represent a distress to patients for 2
      reasons: one is disfigurement, and the other is the increased risk of developing
      secondary melanocytic tumors, such as benign proliferative nodules (BPNs) and
      malignant melanoma (MM). BPN present as a rapid growth nodule arising within a
      congenital melanocytic nevus (CMN) that often ulcerates, occurs in children
      younger than 2 years of age. BPNs arising within a CMN are exceedingly rare after
      childhood, and very few cases have been described in adults. Despite the
      worrisome clinical and histologic findings of BPN, most laboratory investigations
      seem to support their benignity. The distinction between MM and BPN is extremely
      important, but the histopathology of BPN of GCMN can be a challenge to
      differentiate from MM. In the recent years, molecular tests that investigate DNA
      copy number alterations such as fluorescence in situ hybridization and
      comparative genomic hybridization have shown promise to help guide the diagnosis
      of ambiguous melanocytic proliferations arising within CMNs. We report the case
      of a 22-year-old woman with a nodule arising in a GCMN and with an axillary mass
      suggesting a nodal metastasis of melanoma, and discuss the unusual clinical,
      histopathologic, and molecular findings that make this case particularly
      interesting. 

PMID- 25062264
TI  - Hemophagocytosis in Cutaneous Autoimmune Disease.
AB  - BACKGROUND: The significance of the histological visualization of
      hemophagocytosis in tissues depends on the context, varying from a nonspecific
      phenomenon to a characteristic or diagnostic feature for certain disease
      entities. Hemophagocytosis is also one of the key features of macrophage
      activation syndrome (MAS) (hemophagocytic syndrome) a potentially life
      threatening complication of underlying conditions such as infections, malignancy,
      and autoimmune disorders. Clinical manifestations of MAS are high fever,
      pancytopenia, liver dysfunction, and coagulopathy. These clinical symptoms are
      due to an abnormal activation of the immune system in a strong association with
      the cytokine milieu. The diagnosis of MAS may be easily missed; it is usually
      detected in the bone marrow, lymph node, liver, and spleen. Only few reports
      exist in the literature with histological description of cutaneous
      hemophagocytosis as a sign for MAS in patients with lymphoma and infection. In
      this report, the authors present the clinicopathological and immunohistochemical
      features of 3 patients with cutaneous hemophagocytosis, specifically
      erythrophagocytosis, associated with autoimmune disease, and discuss the
      relevance of these findings. OBSERVATION: The authors report 3 patients who
      developed cutaneous hemophagocytosis during the course of an underlying
      autoimmune disorder. One patient suffered from dermatomyositis, the other 2
      patients from systemic lupus erythematosus, whereby one of them was a 3-month old
      girl with neonatal lupus erythematosus. The patient with dermatomyositis
      developed MAS according to the current diagnostic criteria. Although the 2 other
      patients had an acute flare of their autoimmune disease with histological signs
      of cutaneous hemophagocytosis, they did not fulfill the complete criteria for a
      diagnosis of MAS. Histiocyte proliferation and activation with increase of
      cytokines could be demonstrated by immunohistology. CONCLUSIONS: This report is
      the first to describe hemophagocytosis in cutaneous biopsies of patients with
      autoimmune diseases, associated with a complete or incomplete constellation of
      MAS. Key players in this process are histiocytes/macrophages engaged in
      phagocytosis of erythrocytes. Hemophagocytosis observed in skin biopsies may be a
      diagnostic clue for MAS and an indicator for a potentially aggressive course of
      the underlying disease.

PMID- 25062265
TI  - Subungual Acral Fibromyxoma Involving the Bone: A Mimicker of Malignancy.
AB  - Superficial acral fibromyxoma (SAF) is a recently recognized myxoid tumor that
      usually occurs on the fingers and toes of middle-aged adults. We report the case
      of a 53-year-old man with a SAF on the first left toe that had been slowly
      growing for 2 years. Hispathologically, the lesion was nonencapsulated and was
      composed of stellate and spindle cells, arranged in a myxoid matrix. No atypia or
      mitotic figures were found. Neoplastic cells showed positive staining for CD34
      and negative staining for epithelial membrane antigen, actin, desmin, keratins, S
      100 protein, and HMB45. Main differential diagnoses of SAF include benign and
      malignant myxoid and spindle cells tumors, such as myxoid fibrous histiocytoma,
      superficial angiomyxoma, myxoid neurofibroma, myxoid dermatofibrosarcoma
      protuberans, and low-grade fibromyxoid sarcoma. 

PMID- 25062266
TI  - Comparative expression of matrix metalloproteinases in internal malignancies and
      paired cutaneous metastatic lesions.
AB  - BACKGROUND: Matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase
      (TIMP), and membrane-type 1 matrix metalloproteinase (MT1-MMP) are thought to be
      involved in the destruction of basement membrane and stromal invasion by cancer
      cells. OBJECTIVE: The aim of this study was to identify and compare MMP and TIMP
      expression in internal malignancies and paired cutaneous metastatic lesions.
      MATERIALS AND METHODS: We compared the expression of MMP-2, MMP-9, MT1-MMP, and
      TIMP-2 in the internal malignancy and paired cutaneous metastatic lesion using
      immunohistochemical stains. RESULTS: The cutaneous metastatic lesions expressed
      significantly more MMP-2, MMP-9, and MT1-MMP and significantly less TIMP-2 than
      did the paired internal malignancies. In breast cancer, cutaneous metastatic
      lesions expressed significantly more MMP-9 and significantly less TIMP-2 than did
      the primary breast cancer lesion. In lung cancer, the cutaneous metastatic lesion
      expressed significantly more MMP-2 and MT1-MMP than did the primary lesion. In
      stomach cancer, the cutaneous metastatic lesion expressed significantly less TIMP
      2 than did the primary lesion. CONCLUSIONS: Our study demonstrates that cutaneous
      metastatic lesions have different MMPs and TIMP-2 expression patterns compared
      with their paired internal malignancies. Also, MMPs and TIMP-2 expression differs
      according to the type of primary cancer.

PMID- 25062268
TI  - Opposed effects of enzymatic gliotoxin N- and S-methylations.
AB  - Gliotoxin (1), a virulence factor of the human pathogenic fungus Aspergillus
      fumigatus, is the prototype of epipoly(thiodioxopiperazine) (ETP) toxins. Here we
      report the discovery and functional analysis of two methyl transferases (MTs)
      that play crucial roles for ETP toxicity. Genome comparisons, knockouts, and in
      vitro enzyme studies identified a new S-adenosyl-l-methionine-dependent S-MT
      (TmtA) that is, surprisingly, encoded outside the gli gene cluster. We found that
      TmtA irreversibly inactivates ETP by S-alkylation and that this detoxification
      strategy appears to be not only limited to ETP producers. Furthermore, we
      unveiled that GliN functions as a freestanding amide N-MT. GliN-mediated amide
      methylation confers stability to ETP, damping the spontaneous formation of tri-
      and tetrasulfides. In addition, enzymatic N-alkylation constitutes the last step
      in gliotoxin biosynthesis and is a prerequisite for the cytotoxicity of the
      molecule. Thus, these specialized alkylating enzymes have dramatic and fully
      opposed effects: complete activation or inactivation of the toxin. 

PMID- 25062269
TI  - Adult Bland-White-Garland syndrome presenting as a sudden cardiac death:
      successful resuscitation, implantable cardioverter defibrillator and surgery.

PMID- 25062267
TI  - Structural characterization of the Saccharomyces cerevisiae THO complex by small
      angle X-ray scattering.
AB  - The THO complex participates during eukaryotic mRNA biogenesis in coupling
      transcription to formation and nuclear export of translation-competent messenger
      ribonucleoprotein particles. In Saccharomyces cerevisiae, THO has been defined as
      a heteropentamer composed of the Tho2p, Hpr1p, Tex1p, Mft1p, and Thp2p subunits
      and the overall three-dimensional shape of the complex has been established by
      negative stain electron microscopy. Here, we use small-angle X-ray scattering
      measured for isolated THO components (Mft1p and Thp2p) as well as THO
      subcomplexes (Mft1p-Thp2p and Mft1p-Thp2p-Tho2p) to construct structural building
      blocks that allow positioning of each subunit within the complex. To accomplish
      this, the individual envelopes determined for Mft1p and Thp2p are first fitted
      inside those of the Mft1p-Thp2p and Mft1p-Thp2p-Tho2p complexes. Next, the
      ternary complex structure is placed in the context of the five-component electron
      microscopy structure. Our model reveals not only the position of each protein in
      the THO complex relative to each other, but also shows that the pentamer is
      likely somewhat larger than what was observed by electron microscopy. 

PMID- 25062270
TI  - Highly calcific in-stent restenosis as a substrate for sirolimus-eluting stent
      very late stent thrombosis.
AB  - We describe a case of very late stent thrombosis with documentation of highly
      calcific restenosis at optical coherence tomography without clear signs of stent
      malapposition, neoatherosclerosis disruption, or vascular toxicity to stent
      polymer. To the best of our knowledge, this is one of the first reports dealing
      with highly calcific restenosis as a potential background to very late stent
      thrombosis. 

PMID- 25062271
TI  - Voltage-gated potassium channels autoantibodies in a child with rasmussen
      encephalitis.
AB  - Rasmussen encephalitis (RE) is a severe epileptic and inflammatory encephalopathy
      of unknown etiology, responsible for focal neurological signs and cognitive
      decline. The current leading hypothesis suggests a sequence of immune reactions
      induced by an indeterminate factor. This sequence is thought to be responsible
      for the production of autoantibody-mediated central nervous system degeneration.
      However, these autoantibodies are not specific to the disease and not all
      patients present with them. We report the case of a 4-year-old girl suffering
      from RE displaying some atypical features such as fast evolution and seizures of
      left parietal onset refractory to several antiepileptics, intravenous
      immunoglobulins, and corticosteroids. Serum autoantibodies directed against
      voltage-gated potassium channels (VGKC) were evidenced at 739 pM, a finding never
      previously reported in children. This screening was performed because of an
      increased signal in the temporolimbic areas on brain magnetic resonance imaging,
      which was similar to what is observed during limbic encephalitis. The patient
      experienced epilepsia partialis continua with progressive right hemiplegia and
      aphasia. She underwent left hemispherotomy at the age of 5.5 years after which
      she became seizure free with great cognitive improvement. First described in
      adults, VGKC autoantibodies have been recently described in children with various
      neurological manifestations. The implication of VGKC autoantibodies in RE is a
      new observation and opens up new physiopathological and therapeutic avenues of
      investigation. 

PMID- 25062273
TI  - Rapid engineering of versatile molecular logic gates using heterologous genetic
      transcriptional modules.
AB  - We designed and constructed versatile modular genetic logic gates in bacterial
      cells. These function as digital logic 1-input Buffer gate, 2-input and 3-input
      AND gates with one inverted input and integrate multiple chemical input signals
      in customised logic manners. Such rapidly engineered devices serve to achieve
      increased sensing signal selectivity. 

PMID- 25062272
TI  - Nox4: a hydrogen peroxide-generating oxygen sensor.
AB  - Nox4 is an oddity among members of the Nox family of NADPH oxidases [seven
      isoenzymes that generate reactive oxygen species (ROS) from molecular oxygen] in
      that it is constitutively active. All other Nox enzymes except for Nox4 require
      upstream activators, either calcium or organizer/activator subunits (p47(phox),
      NOXO1/p67(phox), and NOXA1). Nox4 may also be unusual as it reportedly releases
      hydrogen peroxide (H2O2) in contrast to Nox1-Nox3 and Nox5, which release
      superoxide, although this result is controversial in part because of possible
      membrane compartmentalization of superoxide, which may prevent detection. Our
      studies were undertaken (1) to identify the Nox4 ROS product using a membrane
      free, partially purified preparation of Nox4 and (2) to test the hypothesis that
      Nox4 activity is acutely regulated not by activator proteins or calcium, but by
      cellular pO2, allowing it to function as an O2 sensor, the output of which is
      signaling H2O2. We find that approximately 90% of the electron flux through
      isolated Nox4 produces H2O2 and 10% forms superoxide. The kinetic mechanism of
      H2O2 formation is consistent with a mechanism involving binding of one oxygen
      molecule, which is then sequentially reduced by the heme in two one-electron
      reduction steps first to form a bound superoxide intermediate and then H2O2;
      kinetics are not consistent with a previously proposed internal superoxide
      dismutation mechanism involving two oxygen binding/reduction steps for each H2O2
      formed. Critically, Nox4 has an unusually high Km for oxygen (~18%), similar to
      the values of known oxygen-sensing enzymes, compared with a Km of 2-3% for Nox2,
      the phagocyte NADPH oxidase. This allows Nox4 to generate H2O2 as a function of
      oxygen concentration throughout a physiological range of pO2 values and to
      respond rapidly to changes in pO2.

PMID- 25062274
TI  - Evaluation of prolonged fatigue post-West Nile virus infection and association of
      fatigue with elevated antiviral and proinflammatory cytokines.
AB  - This study aimed to characterize fatigue postinfection among study participants
      with a history of West Nile virus (WNV) infection and determine whether antiviral
      and pro-inflammatory cytokines were significantly elevated in those reporting
      prolonged fatigue. We found that 31% (44/140) of study participants experienced
      prolonged (more than 6 months) fatigue postinfection, with an average length of
      fatigue duration of 5 years. Females, those younger than 50 years of age, and
      those with symptomatic clinical WNV disease were significantly more likely to
      report fatigue. Pro-inflammatory and antiviral cytokines (granulocyte macrophage
      colony stimulating factor, interferon-gamma, interferon-gamma inducing protein
      10, interleukin 2, interleukin 6, and interleukin 12p70) were significantly
      elevated in those reporting fatigue postinfection compared to those not reporting
      fatigue. Clinicians should consider history of WNV infection as a possible factor
      when evaluating causes of prolonged fatigue following a febrile viral illness in
      their patients.

PMID- 25062275
TI  - Leptospira spp. in rodents and shrews in Germany.
AB  - Leptospirosis is an acute, febrile disease occurring in humans and animals
      worldwide. Leptospira spp. are usually transmitted through direct or indirect
      contact with the urine of infected reservoir animals. Among wildlife species,
      rodents act as the most important reservoir for both human and animal infection.
      To gain a better understanding of the occurrence and distribution of pathogenic
      leptospires in rodent and shrew populations in Germany, kidney specimens of 2973
      animals from 11 of the 16 federal states were examined by PCR. Rodent species
      captured included five murine species (family Muridae), six vole species (family
      Cricetidae) and six shrew species (family Soricidae). The most abundantly trapped
      animals were representatives of the rodent species Apodemus flavicollis,
      Clethrionomys glareolus and Microtus agrestis. Leptospiral DNA was amplified in
      10% of all animals originating from eight of the 11 federal states. The highest
      carrier rate was found in Microtus spp. (13%), followed by Apodemus spp. (11%)
      and Clethrionomys spp. (6%). The most common Leptospira genomospecies determined
      by duplex PCR was L. kirschneri, followed by L. interrogans and L.
      borgpetersenii; all identified by single locus sequence typing (SLST).
      Representatives of the shrew species were also carriers of Leptospira spp. In 20%
      of Crocidura spp. and 6% of the Sorex spp. leptospiral DNA was detected. Here,
      only the pathogenic genomospecies L. kirschneri was identified. 

PMID- 25062276
TI  - Assessing health risk due to exposure to arsenic in drinking water in Hanam
      Province, Vietnam.
AB  - We assessed health risks related to Arsenic (As) in contaminated drinking water
      in Hanam, applying the Australian Environmental Health Risk Assessment Framework,
      which promotes stakeholder involvement in risk assessments. As concentrations in
      300 tube-well water samples, before and after filtration, were analyzed and the
      water consumption levels in 150 households were estimated. Skin cancer risk was
      characterized using Cancer Slope Factor index and lifetime average daily dose
      with a probabilistic approach. The results showed that arsenic concentrations in
      tube-well water ranged from 8-579 ppb (mean 301 ppb) before filtration and
      current sand filters used by the households did not meet the standard for As
      removal. Arsenic daily consumption of 40% of the adults exceeded the level of TDI
      (Tolerable Daily Intake) at 1 ug/kg/day. The average skin cancer risk in adults
      due to consuming filtered tube-well water for drinking purpose were 25.3 * 10-5
      (using only well water) and 7.6 * 10-5 (using both well and rain water). The skin
      cancer risk would be 11.5 times higher if the water was not filtered. Improvement
      of filtration measures or the replacement of the current drinking water sources
      to minimize the health risks to the local population is urgently needed. 

PMID- 25062277
TI  - A new method to monitor the contribution of fast food restaurants to the diets of
      US children.
AB  - BACKGROUND: American adults consume 11.3% of total daily calories from foods and
      beverages from fast food restaurants. The contribution of different types of fast
      food restaurants to the diets of US children is unknown. OBJECTIVE: To estimate
      the consumption of energy, sodium, added sugars, and solid fats among US children
      ages 4-19 y by fast food restaurant type. METHODS: Analyses used the first 24-h
      recall for 12,378 children in the 2003-2010 cycles of the nationally
      representative National Health and Nutrition Examination Survey (NHANES 2003
      2010). NHANES data identify foods by location of origin, including stores and
      fast food restaurants (FFR). A novel custom algorithm divided FFRs into 8
      segments and assigned meals and snacks to each. These included burger, pizza,
      sandwich, Mexican, Asian, fish, and coffee/snack restaurants. The contribution of
      each restaurant type to intakes of energy and other dietary constituents was then
      assessed by age group (4-11 y and 12-19 y) and by race/ethnicity. RESULTS: Store
      bought foods and beverages provided 64.8% of energy, 61.9% of sodium, 68.9% of
      added sugars, and 60.1% of solid fats. FFRs provided 14.1% of energy, 15.9% of
      sodium, 10.4% of added sugars and 17.9% of solid fats. Among FFR segments, burger
      restaurants provided 6.2% of total energy, 5.8% of sodium, 6.2% of added sugars,
      and 7.6% of solid fats. Less energy was provided by pizza (3.3%), sandwich
      (1.4%), Mexican (1.3%), and chicken restaurants (1.2%). Non-Hispanic black
      children obtained a greater proportion of their total energy (7.4%), sodium
      (7.1%), and solid fats (9.5%) from burger restaurants as compared to non-Hispanic
      white children (6.0% of energy, 5.5% of sodium, and 7.3% of solid fat).
      CONCLUSIONS: These novel analyses, based on consumption data by fast food market
      segment, allow public health stakeholders to better monitor the effectiveness of
      industry efforts to promote healthier menu options.

PMID- 25062278
TI  - Babesiosis surveillance, new jersey, USA, 2006-2011.

PMID- 25062279
TI  - Incidence of anticancer drugs in an aquatic urban system: from hospital effluents
      through urban wastewater to natural environment.
AB  - The presence of 10 anticancer drugs was studied along the entire urban water
      cycle -from hospital effluents through urban wastewater treatment plant till
      surface waters- and their potential environmental risk was assessed.
      Azathioprine, etoposide, docetaxel, paclitaxel, methotrexate, cyclophosphamide,
      tamoxifen and ciprofloxacin were detected in hospital effluent and in the urban
      influent of the sewage treatment plant although most of them were totally
      eliminated after WWTP. Only cyclophosphamide, tamoxifen and ciprofloxacin were
      found in both WWTP effluent and in the receiving river at a concentration range
      between nd-20 ng L(-1), 25-38 ng L(-1) and 7-103 ng L(-1) respectively. Tamoxifen
      and ciprofloxacin, commonly used for veterinary practices, were also detected in
      the river upstream the sewage discharge. In addition, they both were considered
      to pose a potential risk to the environment based on the levels found in the WWTP
      effluent together with their ecotoxicological impact in selected organisms. 

PMID- 25062280
TI  - How much do PCB toxic equivalents account for PHAH toxicity in predatory birds?
AB  - Various diffuse polyhalogenated aromatic hydrocarbons (PHAHs) exert common
      toxicity through the aryl hydrocarbon receptor (AhR). Apex predators spatially
      and temporally integrate diffuse contamination and simultaneous exposure can
      cause additive toxicity. We investigated the extent to which PCBs, still amongst
      the most prevalent PHAHs accumulated by predators, accounted for total PHAH
      toxicity in raptors and fish eating birds from Britain. We analysed egg or liver
      extracts from six species and compared chemically determined SigmaPCB-TEQs
      concentrations with total AhR-mediated toxicity determined using the chemical
      activated luciferase gene expression bioassay (CALUX-TEQ). Dioxin-like PCB
      profiles in eggs and livers were dominated by congeners 118, 105 and 167.
      SigmaPCB-TEQ and CALUX-TEQ concentrations were positively associated but not in a
      1:1 relationship. SigmaPCB-TEQ were broadly similar to CALUX-TEQ concentrations
      in eggs and livers with CALUX-TEQ concentrations >50-80 and 160-320 pg g(-1)
      lipid respectively, but were lower than CALUX-TEQ concentrations in less
      contaminated samples. 

PMID- 25062282
TI  - Gigahertz flexible graphene transistors for microwave integrated circuits.
AB  - Flexible integrated circuits with complex functionalities are the missing link
      for the active development of wearable electronic devices. Here, we report a
      scalable approach to fabricate self-aligned graphene microwave transistors for
      the implementation of flexible low-noise amplifiers and frequency mixers, two
      fundamental building blocks of a wireless communication receiver. A devised AlOx
      T-gate structure is used to achieve an appreciable increase of device
      transconductance and a commensurate reduction of the associated parasitic
      resistance, thus yielding a remarkable extrinsic cutoff frequency of 32 GHz and a
      maximum oscillation frequency of 20 GHz; in both cases the operation frequency is
      an order of magnitude higher than previously reported. The two frequencies work
      at 22 and 13 GHz even when subjected to a strain of 2.5%. The gigahertz microwave
      integrated circuits demonstrated here pave the way for applications which require
      high flexibility and radio frequency operations. 

PMID- 25062281
TI  - Shelter dogs as sentinels for Trypanosoma cruzi transmission across Texas.
AB  - Chagas disease, an infection with the parasite Trypanosoma cruzi, is increasingly
      diagnosed among humans in the southern United States. We assessed exposure of
      shelter dogs in Texas to T. cruzi; seroprevalence across diverse ecoregions was
      8.8%. Canine serosurveillance is a useful tool for public health risk assessment.

PMID- 25062283
TI  - Assessing Raman spectroscopy as a prescreening tool for the selection of
      archaeological bone for stable isotopic analysis.
AB  - Stable isotope analyses for paleodiet investigations require good preservation of
      bone protein, the collagen, to obtain reliable stable isotope values. Burial
      environments cause diagenetic alterations to collagen, especially in the leaching
      of the organic bone content. The survival of bone protein may be assessed by the
      weight % collagen, % carbon and % nitrogen yields, but these values are achieved
      only after destructive chemical processing. A non-destructive method of
      determining whether bone is suitably preserved would be desirable, as it would be
      less costly than chemical processing, and would also preserve skeletal
      collections. Raman analysis is one such potential non-destructive screening
      method. In previous applications, Raman spectroscopy has been used to test both
      the alteration of the mineral portion of bone, as well as to indicate the
      relative amount of organic material within the bone structure. However, there has
      been no research to test the relationship between the Raman spectroscopic results
      and the survival of bone protein. We use a set of 41 bone samples from the
      prehistoric archaeological site of Ban Non Wat, Northeast Thailand, to assess if
      Raman spectroscopy analysis of the organic-phosphate ratio has a significant
      correlation with the weight % collagen, and carbon and nitrogen yields obtained
      by isotopic analysis. The correlation coefficients are highly statistically
      significant in all cases (r = 0.716 for collagen, r = 0.630 for carbon and r =
      0.706 for nitrogen, p<=0.001 for all) with approximately or close to half of the
      variation in each explained by variation in the organic-phosphate ratio (51.2%
      for collagen, 39.6% for carbon, and 49.8% for nitrogen). Although the Raman
      screening method cannot directly quantify the extent of collagen survival, it
      could be of use in the selection of bone most likely to have viable protein
      required for reliable results from stable isotope analysis. 

PMID- 25062284
TI  - Ecological accounting based on extended exergy: a sustainability perspective.
AB  - The excessive energy consumption, environmental pollution, and ecological
      destruction problems have gradually become huge obstacles for the development of
      societal-economic-natural complex ecosystems. Regarding the national ecological
      economic system, how to make explicit the resource accounting, diagnose the
      resource conversion, and measure the disturbance of environmental emissions to
      the systems are the fundamental basis of sustainable development and coordinated
      management. This paper presents an extended exergy (EE) accounting including the
      material exergy and exergy equivalent of externalities consideration in a
      systematic process from production to consumption, and China in 2010 is chosen as
      a case study to foster an in-depth understanding of the conflict between high
      speed development and the available resources. The whole society is decomposed
      into seven sectors (i.e., Agriculture, Extraction, Conversion, Industry,
      Transportation, Tertiary, and Domestic sectors) according to their distinct
      characteristics. An adaptive EE accounting database, which incorporates
      traditional energy, renewable energy, mineral element, and other natural
      resources as well as resource-based secondary products, is constructed on the
      basis of the internal flows in the system. In addition, the environmental
      emission accounting has been adjusted to calculate the externalities-equivalent
      exergy. The results show that the EE value for the year 2010 in China was 1.80 *
      10(14) MJ, which is greatly increased. Furthermore, an EE-based sustainability
      indices system has been established to provide an epitomized exploration for
      evaluating the performance of flows and storages with the system from a
      sustainability perspective. The value of the EE-based sustainability indicator
      was calculated to be 0.23, much lower than the critical value of 1, implying that
      China is still developing in the stages of high energy consumption and a low
      sustainability level. 

PMID- 25062285
TI  - Surgical outcomes and natural history of intramedullary spinal cord cavernous
      malformations: a single-center series and meta-analysis of individual patient
      data: Clinic article.
AB  - OBJECT: Information pertaining to the natural history of intramedullary spinal
      cord cavernous malformations (ISCCMs) and patient outcomes after surgery is
      scarce. To evaluate factors associated with favorable outcomes for patients with
      surgically and conservatively managed ISCCMs, the authors performed a systematic
      review and metaanalysis of the literature. In addition, they included their
      single-center series of ISCCMs. METHODS: The authors searched MEDLINE, EMBASE,
      CINAHL, Google Scholar, and The Cochrane Library for studies published through
      June 2013 that reported cases of ISCCMs. Data from all eligible studies were used
      to examine the epidemiology, clinical features, and neurological outcomes of
      patients with surgically managed and conservatively treated ISCCMs. To evaluate
      several variables as predictors of favorable neurological outcomes, the authors
      conducted a meta-analysis of individual patient data and performed univariate and
      multivariate logistic regression analyses. Variables included patient age,
      patient sex, lesion spinal level, lesion size, cerebral cavernomas, family
      history of cavernous malformations, clinical course, presenting symptoms,
      treatment strategy (operative or conservative), symptom duration, surgical
      approach, spinal location, and extent of resection. In addition, they performed a
      meta-analysis to determine a pooled estimate of the annual hemorrhage rate of
      ISCCMs. RESULTS: Eligibility criteria were met by 40 studies, totaling 632
      patients, including the authors' institutional series of 24 patients. Mean
      patient age was 39.1 years (range 2-80 years), and the male-to-female ratio was
      1.1:1. Spinal levels of cavernomas were cervical (38%), cervicothoracic (2.4%),
      thoracic (55.2%), thoracolumbar (0.6%), lumbar (2.1%), and conus medullaris
      (1.7%). Average cavernoma size was 9.2 mm. Associated cerebral cavernomas
      occurred in 16.5% of patients, and a family history of cavernous malformation was
      found for 11.9% of evaluated patients. Clinical course was acute with stepwise
      progression for 45.4% of patients and slowly progressive for 54.6%. Symptoms were
      motor (60.5%), sensory (57.8%), pain (33.8%), bladder and/or bowel (23.6%),
      respiratory distress (0.5%), or absent (asymptomatic; 0.9%). The calculated
      pooled annual rate of hemorrhage was 2.1% (95% CI 1.3%-3.3%). Most (89.9%)
      patients underwent resection, and 10.1% underwent conservative management
      (observation). Outcomes were better for those who underwent resection than for
      those who underwent conservative management (OR 2.79, 95% CI 1.46-5.33, p =
      0.002). A positive correlation with improved neurological outcomes was found for
      resection within 3 months of symptom onset (OR 2.11, 95% CI 1.31-3.41, p =
      0.002), hemilaminectomy approach (OR 3.20, 95% CI 1.16-8.86, p = 0.03), and gross
      total resection (OR 3.61, 95% CI 1.24-10.52, p = 0.02). Better outcomes were
      predicted by an acute clinical course (OR 1.72, 95% CI 1.10-2.68, p = 0.02) and
      motor symptoms (OR 1.76, 95% CI 1.08-2.86, p = 0.02); poor neurological recovery
      was predicted by sensory symptoms (OR 0.58, 95% CI 0.35-0.98, p = 0.04). Rates of
      neurological improvement after resection were no higher for patients with
      superficial ISCCMs than for those with deep-seated ISCCMs (OR 1.36, 95% CI 0.71
      2.60, p = 0.36). CONCLUSIONS: Intramedullary spinal cord cavernous malformations
      tend to be clinically progressive. The authors' findings support an operative
      management plan for patients with a symptomatic ISCCM. Surgical goals include
      gross-total resection through a more minimally invasive hemilaminectomy approach
      within 3 months of presentation.

PMID- 25062286
TI  - Nerve growth factor promotes expression of novel genes in intervertebral disc
      cells that regulate tissue degradation: Laboratory investigation.
AB  - OBJECT: Increased neurotrophin activity in degenerative intervertebral discs
      (IVDs) is one potential cause of chronic low-back pain (LBP). The aim of the
      study was to assess if nerve growth factor (NGF) might alter gene expression of
      IVD cells and contribute to disc degeneration by enhancing expression or activity
      of factors that cause breakdown of IVD matrix. METHODS: Rat-tail IVD cells were
      stimulated by NGF and subjected to microarray analysis. Real-time polymerase
      chain reaction, Western blotting, and immunocytochemistry of rat and human IVD
      cells and tissues treated with NGF in vitro in the absence or presence of the NGF
      inhibitor Ro 08-2750 were used to confirm findings of the microarray studies.
      Phosphorylation of mitogen-activated protein kinase (MAPK) was used to identify
      cell signaling pathways involved in NGF stimulation in the absence or presence of
      Ro 08-2750. RESULTS: Microarray analysis demonstrated increased expression of
      chitinase 3-like 1 (Chi3l1), lipocalin 2 (Lcn2), and matrix metalloproteinase-3
      (Mmp3) following NGF stimulation of rat IVD cells in vitro. Increased gene
      expression was confirmed by real-time polymerase chain reaction with a relative
      increase in the Mmp/Timp ratio. Increased expression of Chi3l1, Lcn2, and Mmp3
      following NGF stimulation was also demonstrated in rat cells and human tissue in
      vitro. Effects of NGF on protein expression were blocked by an NGF inhibitor and
      appear to function through the extracellular-regulation kinase 1/2 (ERK1/2) MAPK
      pathway. CONCLUSIONS: Nerve growth factor has potential effects on matrix
      turnover activity and influences the catabolic/anabolic balance of IVD cells in
      an adverse way that may potentiate IVD degeneration. Anti-NGF treatment might be
      beneficial to ameliorate progressive tissue breakdown in IVD degeneration and may
      lead to pain relief.

PMID- 25062287
TI  - An open-label pilot trial of N-acetylcysteine and varenicline in adult cigarette
      smokers.
AB  - BACKGROUND: Varenicline (VAR) has demonstrated superior efficacy over other
      smoking cessation pharmacotherapies, though 50-60% of those treated do maintain
      abstinence. Some preclinical findings suggest that new nicotine dependence
      pharmacotherapies should target the glutamatergic system, given its demonstrated
      role in addiction. Attention has been given to N-acetylcysteine (NAC), which
      appears to restore normal glutamate signaling in animal models. It is possible
      that NAC and VAR may work in concert to promote abstinence at higher rates than
      with either medication alone. OBJECTIVE: To demonstrate the feasibility and
      safety of co-administering NAC and VAR in nicotine-dependent participants.
      METHODS: Participants (n = 19) were daily cigarette smokers, and did not need to
      be seeking treatment. They received 4 weeks of open-label treatment with NAC
      (1200 mg twice daily) and VAR (1 mg twice daily, following titration) and were
      assessed weekly for adverse events (AEs), smoking, craving and withdrawal.
      RESULTS: Sixteen participants reported a total of 40 AEs, and most were mild
      (88%). The most commonly reported AE was nausea (15%). Medication adherence,
      assessed via self-reports and pill counts, was excellent (98%). Exploratory
      analyses showed reductions in cigarettes per day, though point prevalence
      abstinence at the end of the study was low. CONCLUSIONS: These preliminary data
      provide the first demonstration of safety and feasibility of the co
      administration of NAC and VAR in cigarette smokers. AEs were consistent with
      those typically reported for VAR and NAC. These data support future efficacy
      research on NAC and VAR for smoking cessation.

PMID- 25062288
TI  - Steviol glycoside rebaudioside A induces glucagon-like peptide-1 and peptide YY
      release in a porcine ex vivo intestinal model.
AB  - Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones important for
      satiation and are involved in the process called "ileal brake". The aim of this
      study was to investigate the GLP-1- and PYY-stimulating efficacy of rebaudioside
      A, casein, and sucrose. This was studied using tissue segments collected from
      various regions of the pig small intestine. GLP-1 release was strongest from the
      distal ileum. There, control release was 0.06 +/- 0.01 (GLP-1) and 0.07 +/- 0.01
      (PYY) pmol/cm(2) of tissue. Rebaudioside A (2.5, 12.5, and 25 mM) stimulated GLP
      1 release (0.14 +/- 0.02, 0.16 +/- 0.02, and 0.13 +/- 0.02 pmol/cm(2) of tissue,
      p < 0.001) and PYY release (0.19 +/- 0.02, 0.42 +/- 0.06, and 0.27 +/- 0.03
      pmol/cm(2) of tissue, p < 0.001). Sucrose stimulated GLP-1 release (0.08 +/- 0.01
      pmol/cm(2) of tissue, p < 0.05) only at 10 mM. Casein (0.5%, 1%, and 2.5%, w/v)
      stimulated GLP-1 release (0.15 +/- 0.03, 0.13 +/- 0.02, and 0.14 +/- 0.01
      pmol/cm(2) of tissue, p < 0.001) and PYY release (0.13 +/- 0.02, 0.20 +/- 0.03,
      and 0.27 +/- 0.03 pmol/cm(2) of tissue, p < 0.01). These findings may help in
      developing dietary approaches for weight management. 

PMID- 25062289
TI  - The assessment of arterial stiffness in pre-eclamptic patients.

PMID- 25062291
TI  - Should pediatric emergency physicians be decentralized in the medical community?
AB  - INTRODUCTION: Pediatric emergency physicians (PEPs) are well established as
      primary emergency department (ED) providers in dedicated pediatric centers and
      university settings. However, the optimum role of these subspecialists is less
      well defined in the community hospital environment. This study examined the
      impact on the ED care of children after the introduction of 10 PEPs into a
      simulated medical community. METHODS: A computer-generated community was created,
      containing 10 community hospitals treating 250,000 pediatric ED patients.
      Children requiring ED treatment received their care at the closest ED to their
      location. Ten PEPs were introduced into the community, and their impact on
      patient care was examined under 2 different models. In a restrictive model, the
      PEPs established 2 full-time pediatric EDs within the 2 busiest hospitals,
      whereas, in a distributive model, the PEPs were distributed throughout the 8
      busiest hospitals. In the 8-hospital model, the PEPs provided direct patient care
      along with the general emergency physicians in that facility and also provided
      educational, administrative, and performance improvement support for the
      department. In the restrictive model, the PEPs impacted the care of 100% of the
      children presenting for treatment at their 2 practice sites. In the distributive
      model, impact included the direct patient care by the PEP but also included
      changes produced in the care provided by the general emergency physicians at the
      site. Three different levels of impact were considered for the presence of the
      PEPs: a low-impact version in which the PEPs' presence only impacted 25% of the
      children at that site, a moderate-impact version in which the impact affected 50%
      of the children, and a high-impact version in which the impact affected 75% of
      the children. A secondary analysis was performed to account for the possibility
      of patients self-diverting from the closest ED to 1 of the pediatric EDs in the
      restrictive model. RESULTS: In the restrictive model, the addition of 10 PEPs to
      the community would impact 27% of the pediatric ED care in the community. In the
      3 distributive models, the PEPs would impact 23% of pediatric care in the low
      impact version, 46% of pediatric care in the moderate-impact version, and 69% of
      pediatric care in the high-impact version. If self-diversion were to occur in the
      restrictive model, then 19% of the patients would need to bypass the closest ED
      and travel to the pediatric ED to match the same effect on patient care produced
      in the moderate-impact version of the distributive model and 46% would need to
      divert to match the effect of the high-impact version. CONCLUSIONS: The greatest
      impact of PEPs on an ED population of children is produced when the PEPs
      distribute themselves throughout a medical community rather than create
      individual pediatric EDs in a small number of hospitals.

PMID- 25062290
TI  - Memory outcome one year after stereotactic interstitial radiosurgery in patients
      with epilepsy due to hypothalamic hamartomas.
AB  - Epileptic seizures caused by hypothalamic hamartomas (HHs) are highly
      pharmacoresistant. Resective surgical approaches have shown some efficacy in
      controlling seizures; however, they bear a significant risk of postoperative
      mnemonic deterioration due to the close anatomical proximity of the HHs to
      structures essential for memory functions. We report on cognitive outcome in 26
      patients with structural epilepsy due to HHs one year after interstitial
      radiosurgery. Individually, deteriorations occurred more frequently in
      declarative memory functions (in 20 to 50% of the patients), whereas more than
      80% of the patients revealed stable or even improved performance in attentional
      functions. Preoperative better memory functions were associated with higher risk
      of postoperative performance decline. After radiosurgery, half of the patients
      showed more than 50%, and some up to 90%, of seizure reduction. Hypothalamic
      hamartoma volumes were significantly reduced at follow-up. Transient radiogenic
      edema found in 10/26 patients was not associated with further cognitive decline
      after radiosurgery. These results are highly relevant for therapeutic decisions
      and patient consultation on timing and choice of nonmedical treatment options for
      HHs. 

PMID- 25062292
TI  - Motivation to quit smoking in parental smokers in the pediatric emergency
      department.
AB  - OBJECTIVE: To examine if motivation to quit is associated with parental smoker's
      perceived presence of a personal or child health illness or risk due to tobacco
      use. DESIGN/METHODS: This was a cross-sectional study of a convenience sample of
      218 parental smokers who presented to the pediatric emergency department with
      their child. We assessed factors related to motivation to quit, including
      personal and child smoking-related illness, perceived personal and child health
      risk, smoking behaviors, and demographic characteristics. Motivation to quit was
      measured using the Contemplation Ladder score. RESULTS: The mean score on the
      Contemplation Ladder was 6.2 (SD, 2.5), representing the response: thinking about
      cutting down or quitting . Eighty-four participants (39%) had high motivation to
      quit (Contemplation Ladder score 8). Bivariate analysis showed significant
      associations between high motivation to quit and perceived child health risk with
      continued smoking and perceived personal and child health benefit following
      smoking cessation. Parents with high motivation to quit were more likely to have
      high perceived self-efficacy and confidence in their ability to quit, prior quit
      attempts, and lower nicotine dependence. With the exception of race/ethnicity,
      demographic variables were not associated with motivation to quit. CONCLUSIONS: A
      significant proportion of parental smokers who present to the pediatric emergency
      department endorse strong motivation to quit. Parents who endorse health risk or
      quitting-related health benefits in their child are more likely to have high
      motivation to quit smoking. Future studies are needed to determine if high
      motivation translates into smoking cessation.

PMID- 25062293
TI  - Effectiveness of intravenous levetiracetam as an adjunctive treatment in
      pediatric refractory status epilepticus.
AB  - OBJECTIVES: Intravenous levetiracetam (LEV) has been shown to be effective and
      safe in treating adults with refractory status epilepticus (SE). We sought to
      investigate the efficacy and safety of intravenous LEV for pediatric patients
      with refractory SE. METHODS: We performed a retrospective medical-record review
      of pediatric patients who were treated with intravenous LEV for refractory SE.
      Clinical information regarding age, sex, seizure type, and underlying
      neurological status was collected. We evaluated other anticonvulsants that were
      used prior to administration of intravenous LEV and assessed loading dose,
      response to treatment, and any adverse events from intravenous LEV
      administration. RESULTS: Fourteen patients (8 boys and 6 girls) received
      intravenous LEV for the treatment of refractory SE. The mean age of the patients
      was 4.4 +/- 5.5 years (range, 4 days to 14.6 years). Ten of the patients were
      neurologically healthy prior to the refractory SE, and the other 4 had been
      previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was
      26 +/- 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of
      the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years
      showed seizure termination. No immediate adverse events occurred during or after
      infusions. CONCLUSIONS: The current study demonstrated that the adjunctive use of
      intravenous LEV was effective and well tolerated in pediatric patients with
      refractory SE, even in patients younger than 2 years. Intravenous LEV should be
      considered as an effective and safe treatment option for refractory SE in
      pediatric patients.

PMID- 25062294
TI  - Rate of and risk factors for early recurrence in patients with febrile seizures.
AB  - OBJECTIVE: Patients with febrile seizures (FSs) are observed in emergency
      departments or admitted to hospitals because of the possibility of recurrence.
      There are no guidelines regarding the observation time for recurring FS. The aim
      of this study was to identify the rate, time, risk factors, and cumulative
      probability of early recurrence. PATIENTS AND METHODS: This study was a
      retrospective chart review of patients visiting an emergency department with FS
      from January to December 2011. Early recurrence was defined as FS recurring
      within 7 days after the first episode. Patients were divided into 2 groups: early
      recurrence and nonearly recurrence. The 2 groups were compared in terms of
      demographics, clinical data, and laboratory findings to identify risk factors for
      early recurrence. The cumulative probability over time was determined. RESULTS:
      In total, 228 patients were identified. The recurrence rate was 17.5% (40/228),
      and the median time to recurrence was 6.0 hours (interquartile range, 1.1-13.0
      hours). The overall cumulative probability of early recurrence was 8.8% within 6
      hours, 12.7% within 12 hours, and 15.8% within 24 hours. Most recurrences (90.0%)
      occurred within 24 hours of the first FS. Early recurrence occurred frequently in
      patients with nongeneralized-type seizures or seizures of 15-minute duration or
      longer. CONCLUSIONS: The majority of recurrent FSs occurred in the first 24
      hours. The type and duration of seizures were significant risk factors for early
      recurrence.

PMID- 25062295
TI  - Epidemiology of hospital-based emergency department visits due to sports
      injuries.
AB  - BACKGROUND: Sports-related injuries in adolescents incur a significant amount of
      hospital resources. Sports-related injuries are not an uncommon cause of ED
      visit; however, national estimates of such injuries in teenagers are unknown.
      OBJECTIVES: The aim of this study was to identify and characterize emergency
      department (ED) visits that result from sports-related injuries among teenagers
      across the United States. This study describes the outcomes associated with
      sports-related injuries necessitating ED visits among teenagers at a national
      level. STUDY DESIGN: This is a descriptive epidemiology study. METHODS: The 2008
      Nationwide Emergency Department Sample data set, the largest all-payer health
      care database in the United States, was used to identify ED visits with external
      cause of injury related to sports occurring in patients aged 13 through 19 years.
      Outcomes examined included discharge status after the ED visit and presence of
      concomitant injuries. Descriptive statistics was used to summarize the estimates.
      Nationwide representative estimates were computed using the discharge weight
      variable. RESULTS: There were 432,609 ED visits by those between the ages of 13
      and 19 years who experienced sports-related injuries, with total charges close to
      $447.4 million, with a mean total per-visit charge of $1205. The male patients
      accounted for 76.8% of the total ED visits. The most frequently occurring
      injuries were superficial injury or contusion (n = 118,250 ED visits); sprains
      and strains (n = 105,476); fracture of the upper limb (n = 63,151); open wounds
      of the head, the neck, and the trunk (n = 46,176); as well as intracranial injury
      (n = 30,726). Close to 29% of all ED visits occurred among those residing in
      geographical areas with median household income levels of greater than $64,000.
      After the ED visit, 1.6% were admitted to the same hospital, with a mean length
      of stay of 2.4 days and a mean hospital charge for ED visit and inpatient
      services of $22,703. The male patients composed 87.5% of the hospitalizations.
      The total of hospitalization charges across the entire United States was $154.8
      million. CONCLUSIONS: Sports injuries account for a substantial number of 2008
      teenage ED visits in the United States. Patient- and hospital-level
      characteristics were analyzed and highlighted.

PMID- 25062296
TI  - Adolescents' and young adults' perspectives on their emergency care.
AB  - OBJECTIVES: The aim of this study was to assess the perspectives of adolescents
      and young adults seen in the emergency department (ED) on the optimal age for
      transition from a pediatric ED (PED) to an adult ED (AED) as well as the
      appropriateness of their assigned ED site. Secondary aims were to determine ED
      physicians' understanding and assessment of their psychosocial needs, to
      determine whether subjects had a primary care provider (PCP), as well as to
      identify resources they felt would improve their ED experience. METHODS: This
      study used in-person structured interviews on a convenience sample of ED patients
      aged 15 to 25 years. Data were analyzed with the SPSS for Windows (v15.0) using t
      tests and uncertainty coefficients. RESULTS: We interviewed 200 subjects; the
      mean age was 20.5 (SD, 3) years, 65% were female, and 54% were seen in the PED.
      The subjects reported a mean age of 18.5 years as optimal for transition to an
      AED (mode, 18; second peak, 21); only 5% chose an age older than 21 years. The
      AED subjects more likely felt that their site of care was appropriate (Likert
      scale, 1-3; 2.5 vs 2.2, P < 0.05). HEADSS (Home, Education/Employment, Activity,
      Drugs, Sexuality, Suicide) topics were rarely addressed in both ED sites. The PED
      subjects more often identified a PCP (87% vs 68%); there was no difference in
      notifying their PCP (27% vs 19%). The PED subjects more often desired magazines
      (83% vs 70%) and entertainment videos (61% vs 34%). CONCLUSIONS: Adolescents and
      young adults identify the age of 18 years as optimal for transition from a PED to
      an AED setting. Instituting a standardized HEADSS assessment protocol and
      offering age-appropriate resources may enhance the emergency experience for this
      population.

PMID- 25062297
TI  - J-splint use for temporizing management of pediatric femur fractures: a review of
      18 cases.
AB  - OBJECTIVES: Pediatric femoral fractures are common injuries encountered in the
      field and in emergency departments. Currently described temporizing management
      strategies include skeletal traction, skin traction, traction splinting, and
      posterior splinting, all of which are suboptimal in some instances. J-splinting
      femur fractures may be advantageous in temporizing management of pediatric femur
      fractures. The objective of this study was to evaluate the safety and
      effectiveness of J-splint use for temporizing management of pediatric femur
      fractures. METHODS: This study used a retrospective review of 18 pediatric
      patients with femur fractures treated with J-splinting in the emergency
      department. Patient age, weight, and presplinting and postsplinting pain scale
      ratings were recorded, as well as presplint and postsplint anteroposterior and
      lateral radiographic fracture angulation. Pain before and after J-splinting was
      compared using a paired t test. RESULTS: The mean age of this cohort was 5.4
      years (range, 6 months-13 y), with a mean weight of 21.1 kg (range, 7.7-57 kg).
      In this cohort, there was a significant reduction in pain after reduction and
      splinting from a mean of 6 to a mean of 1 (P < 0.001). No significant difference
      in fracture alignment was noted after J-splinting. No complications were noted.
      CONCLUSIONS: The J-splint is a reliable, simple, and rapidly applied splint that
      prevents many of the complications and downfalls of other described temporizing
      measures and helps to provide excellent pain management in the acute setting.

PMID- 25062298
TI  - The role of medical home in emergency department use for children with
      developmental disabilities in the United States.
AB  - OBJECTIVE: Children with developmental disabilities (DDs) have higher rates of
      emergency department use (EDU) than their typically developing peers do. This
      study sought to elucidate the relationship between EDU frequency and access to a
      comprehensive medical home for children with DD. METHODS: This study conducted
      multivariate logistic regression analysis on data from the 2005-2006 National
      Survey of Children with Special Health Care Needs to explore the association
      between EDU frequency among children with DD and medical home. RESULTS: Compared
      with children with DD reporting zero EDU, children with 3 or more EDU were less
      likely to report access to usual health care source (adjusted odds ratio [AOR],
      0.63; 95% confidence interval [CI], 0.45-0.88). Moreover, children with DD who
      had 3 or more EDU were less likely to have clinicians who listen to parental
      concerns (AOR, 0.58; 95% CI, 0.45-0.76), demonstrate sensitivity toward family
      values and customs (AOR = 0.60, 95% CI = 0.46, 0.78), and build meaningful family
      partnerships (AOR, 0.69; 95% CI, 0.53-0.89). CONCLUSIONS: The study suggests that
      children with DD reporting 3 or more EDU per year would likely reduce their EDU
      by having access to usual source of primary care services and to clinicians with
      skills in building meaningful partnership with the parents. The inclusion of
      these medical home attributes in the adoption of patient-centered medical homes
      with the implementation of the Affordable Care Act presents a mechanism to
      improve care at lower cost as well as facilitate chronic disease management and
      coordination between emergency medicine and primary care physicians that may lead
      to reductions in EDU and unnecessary hospitalization.

PMID- 25062299
TI  - Dispersion morphology and correlation to moduli using buckling metrology in clay
      biopolymer nanocomposite thin films.
AB  - Structure-interaction-mechanical property correlation in bionanocomposite thin
      films is an area of growing interest for research and application areas from
      barrier to molecular transport to UV blocking layers for polymer solar cells to
      dielectric properties modification. Here we study flow coated ultrathin to thin
      films (70-150 nm) of clay bionanocomposites to understand the nanoparticle
      dispersion and its effect on nanomechanical properties. Binary and ternary thin
      film systems of polylactide (PLA), polycaprolactone (PCL), and Cloisite 30B
      (C30B) clay platelets were investigated. While C30B was only partially
      intercalated by PLA, it was almost completely intercalated by PCL due to strong
      hydrogen bonding. In addition, the dispersion of C30B improved continuously and
      linearly with increasing PCL content in homogeneously cast blended PLA:PCL.
      GIWAXS confirmed that the intercalated clay platelets in PLA and PCL were
      dominantly oriented parallel to the substrate. The method of strain induced
      elastic buckling instability for mechanical measurements (SIEBIMM) showed that
      pure PLA and PCL had in-plane modulus unchanged from bulk values for this range
      of ultrathin-thin films. In PLA/C30B nanocomposite thin films, the in-plane
      elastic modulus rapidly increased by up to 26% with 2 wt % C30B, but saturated
      thereafter up to 10 wt % C30B forming C30B aggregates. On the other hand, the in
      plane elastic modulus of PCL/C30B thin films increased linearly by up to 43% with
      10 wt % C30B due to the higher interaction driven dispersion, results that were
      shown to fit well with the Halpin-Tsai model. We conclude that the different
      strengthening behavior came from different interaction driven dispersion states
      of C30B in polymer matrices, governed by their molecular structures. 

PMID- 25062300
TI  - Do hospitals cross-subsidize?
AB  - Despite its salience as a regulatory tool to ensure the delivery of unprofitable
      medical services, cross-subsidization of services within hospital systems has
      been notoriously difficult to detect and quantify. We use repeated shocks to a
      profitable service in the market for hospital-based medical care to test for
      cross-subsidization of unprofitable services. Using patient-level data from
      general short-term hospitals in Arizona and Colorado before and after entry by
      cardiac specialty hospitals, we study how incumbent hospitals adjusted their
      provision of three uncontested services that are widely considered to be
      unprofitable. We estimate that the hospitals most exposed to entry reduced their
      provision of psychiatric, substance-abuse, and trauma care services at a rate of
      about one uncontested-service admission for every four cardiac admissions they
      stood to lose. Although entry by single-specialty hospitals may adversely affect
      the provision of unprofitable uncontested services, these findings warrant
      further evaluation of service-line cross-subsidization as a means to finance
      them. 

PMID- 25062301
TI  - Multifocal intraparenchymal hemorrhages after ventriculoperitoneal shunt surgery
      in infants.
AB  - OBJECT: Ventriculoperitoneal (VP) shunt surgery is the most common treatment for
      hydrocephalus. In certain situations, uncommon complications can occur after
      shunting procedures. The authors undertook this study to analyze the clinical
      characteristics of pediatric patients who developed multifocal intraparenchymal
      hemorrhages (MIPHs) as a complication of shunt surgery. The authors also analyzed
      the risk factors for MIPH in a large cohort of patients with hydrocephalus.
      METHODS: This study included all pediatric patients (age < 18 years) who
      underwent VP shunt surgery at the authors' institution between January 2001 and
      December 2012. During this period, 507 VP shunt operations were performed in 330
      patients. Four of these patients were subsequently diagnosed as having MIPH. The
      authors analyzed the clinical characteristics of these patients in comparison
      with those of the entire group of shunt-treated patients. RESULTS: The incidence
      of MIPH was 1.2% (4 of 330 cases) for all pediatric patients who underwent VP
      shunt placement but 2.9% (4 of 140 cases) for infants less than 1 year old. When
      the analysis was limited to patients whose corrected age was less than 3 months,
      the incidence was 5.3% (4 of 76 cases). Of the 4 patients with MIPH, 2 were male
      and 2 were female. Their median age at surgery was 54 days (range 25-127 days),
      and in all 4 cases, the patients' corrected age was less than 1 month. Three
      patients were preterm infants, whereas one patient was full-term. None of these
      patients had a prior history of intracranial surgery (including CSF diversion
      procedures). All showed severe hydrocephalus during the preoperative period.
      Their clinical courses as patients with MIPH were comparatively favorable,
      despite the radiological findings. CONCLUSIONS: MIPH is a rare but not negligible
      complication of VP shunt surgery. This complication might be a unique phenomenon
      in infants, especially young, preterm infants with severe hydrocephalus.
      Moreover, the absence of previous intracranial procedures might be one of the
      risk factors for this complication. The rapid alteration of brain conditions in
      the setting of immaturity might cause MIPH. To prevent this complication, the
      authors recommend that pressure settings of programmable valves should be
      gradually adapted to the target pressure.

PMID- 25062302
TI  - Pediatric posterior reversible encephalopathy syndrome presenting with isolated
      cerebellar edema and obstructive hydrocephalus.
AB  - In this report, the authors describe the case of a teenage boy who presented with
      hypertensive emergency, posterior reversible encephalopathy syndrome, and
      hydrocephalus due to fourth ventricle outlet obstruction. Posterior reversible
      encephalopathy syndrome is a well-characterized but uncommon syndrome in children
      that is generally triggered by severe hypertension. The unusual clinical picture
      of this patient, who had isolated cerebellar edema leading to obstructive
      hydrocephalus, has been rarely described in children. 

PMID- 25062303
TI  - Recurrence after gross-total resection of low-grade pediatric brain tumors: the
      frequency and timing of postoperative imaging.
AB  - OBJECT: Low-grade glial and glioneuronal brain tumors are frequently encountered
      in the pediatric population and can be effectively treated by resection. The
      authors aimed to use imaging to evaluate how often tumors recurred and to
      determine if recurrences were associated with any clinical symptoms, along with
      the financial costs of imaging, in patients with radiographically proven gross
      total resection (GTR) at Boston Children's Hospital. These data were assessed to
      propose guidelines regarding postoperative surveillance. METHODS: The authors
      performed a retrospective cohort analysis of the Pediatric Brain Tumor Program
      database from 1993 to 2003 to identify patients with glial or glioneuronal tumors
      initially evaluated at Boston Children's Hospital. Among the 888 patients
      evaluated for any type of brain tumor during this period, 67 patients had WHO
      Grade I glial or glioneuronal lesions with radiographically proven GTR and
      available follow-up data. The frequency and timing of postoperative imaging was
      compared with the institutional protocol. Recurrence-free survival was calculated
      using the Kaplan-Meier method. Financial costs of imaging were available from
      2001 to 2009 and were averaged to extrapolate the postoperative surveillance
      costs. RESULTS: Among the 67 patients with GTR, 13 recurrences were detected
      radiographically with a mean time to recurrence of 32.4 months (range 2.9-128.5
      months). The mean duration of follow-up after surgery was 6.6 years. The
      recurrence-free survival at 2 and 5 years after GTR for all low-grade glial and
      glioneuronal tumors was 0.90 (95% CI 0.82-0.97) and 0.82 (95% CI 0.73-0.92),
      respectively. No clinical symptoms were associated with any of the recurrences,
      and no deaths occurred. Under the institutional protocol of surveillance imaging,
      the estimated cost per recurrence at 5 years was $104,094 per patient. The
      proposed protocol would reduce the number of MR scans in the first 5 years from
      10 to 5, providing a potential cost savings of $52,047 per recurrence.
      CONCLUSIONS: Given the slow-growing, clinically asymptomatic nature of low-grade
      glial and glioneuronal tumors coupled with the financial and psychological costs
      of repeated imaging, the authors propose a postoperative surveillance MRI
      schedule that is less intensive than current institutional practice.

PMID- 25062304
TI  - Spontaneous out-of-body experience in a child with refractory right
      temporoparietal epilepsy.
AB  - The authors describe the case of a spontaneous out-of-body experience (OBE) in a
      15-year-old right-handed boy with intractable epilepsy in whom psychosis had been
      misdiagnosed. After successful resection of a right temporoparietal focal
      cortical dysplasia, the OBE and seizures resolved. The authors analyzed the
      underlying causes of the OBE and discussed the mechanism of the OBE caused by an
      epileptic lesion. 

PMID- 25062305
TI  - Atypical location and clinical behavior of a subset of intracranial germ cell
      tumors in children younger than 3 years of age.
AB  - The authors describe a series of 15 intracranial germ cell tumors (IGCTs)
      excluding mature teratomas; 3 cases in children younger than 3 years of age who
      were treated at 3 different international institutions over the course of 20
      years, and 12 from a PubMed search. These tumors, with possible in utero origins,
      often occur in atypical locations. The clinical behavior differed significantly
      from these tumors' counterparts in older children. In this young age group
      germinoma is highly aggressive, whereas nongerminomatous germ cell tumors may be
      cured without radiotherapy. Ongoing genomic studies reveal insights to attain an
      understanding of the biology of these tumors. New treatment strategies are needed
      to improve outcomes for IGCTs in this age group, particularly for germinomas. 

PMID- 25062306
TI  - Preparedness for threat of chikungunya in the pacific.
AB  - Chikungunya virus (CHIKV) caused significant outbreaks of illness during 2005
      2007 in the Indian Ocean region. Chikungunya outbreaks have also occurred in the
      Pacific region, including in Papua New Guinea in 2012; New Caledonia in April
      2013; and Yap State, Federated States of Micronesia, in August 2013. CHIKV is a
      threat in the Pacific, and the risk for further spread is high, given several
      similarities between the Pacific and Indian Ocean chikungunya outbreaks. Island
      health care systems have difficulties coping with high caseloads, which
      highlights the need for early multidisciplinary preparedness. The Pacific Public
      Health Surveillance Network has developed several strategies focusing on
      surveillance, case management, vector control, laboratory confirmation, and
      communication. The management of this CHIKV threat will likely have broad
      implications for global public health. 

PMID- 25062307
TI  - Metal contamination of sediment by paint peeling from abandoned boats, with
      particular reference to lead.
AB  - Fragments of flaking paint have been sampled from eighteen boats (including
      sailing barges, houseboats, a trawler and a ferry) abandoned on the intertidal
      mudflats of two estuaries in eastern England and analysed for Cu, Pb and Zn by X
      ray fluorescence (XRF) spectrometry. Median concentrations of Pb on each boat
      ranged from about 350 to 35,000 MUg g(-1), with individual concentrations
      exceeding 200,000 MUg g(-1) in several cases. Median concentrations of Cu and Zn
      ranged from about 50 to 1900 MUg g(-1) and 50 to 10,000 MUg g(-1), respectively,
      with respective maxima of 172,000 MUg g(-1) and 239,000 MUg g(-1). Because of
      peeling paint, local sediment (analysed by ICP following acid digestion) was
      often measurably contaminated by the metals and, based on median, Al-normalised
      enrichment factors, in the order Pb>Zn>Cu. Due to its abundance and persistence
      in old paints, Pb is of greatest concern from both environmental and human health
      perspectives.

PMID- 25062309
TI  - Assessing the impact of the Draft Bill that never made it.

PMID- 25062308
TI  - The association of genotype-based inbreeding coefficient with a range of physical
      and psychological human traits.
AB  - Across animal species, offspring of closely related mates exhibit lower fitness,
      a phenomenon called inbreeding depression. Inbreeding depression in humans is
      less well understood because mating between close relatives is generally rare and
      stigmatised, confounding investigation of its effect on fitness-relevant traits.
      Recently, the availability of high-density genotype data has enabled
      quantification of variation in distant inbreeding in 'outbred' human populations,
      but the low variance of inbreeding detected from genetic data in most outbred
      populations means large samples are required to test effects, and only a few
      traits have yet been studied. However, it is likely that isolated populations, or
      those with a small effective population size, have higher variation in inbreeding
      and therefore require smaller sample sizes to detect inbreeding effects. With a
      small effective population size and low immigration, Northern Finland is such a
      population. We make use of a sample of ~5,500 'unrelated' individuals in the
      Northern Finnish Birth Cohort 1966 with known genotypes and measured phenotypes
      across a range of fitness-relevant physical and psychological traits, including
      birth length and adult height, body mass index (BMI), waist-to-hip ratio, blood
      pressure, heart rate, grip strength, educational attainment, income, marital
      status, handedness, health, and schizotypal features. We find significant
      associations in the predicted direction between individuals' inbreeding
      coefficient (measured by proportion of the genome in runs of homozygosity) and
      eight of the 18 traits investigated, significantly more than the one or two
      expected by chance. These results are consistent with inbreeding depression
      effects on a range of human traits, but further research is needed to replicate
      and test alternative explanations for these effects. 

PMID- 25062310
TI  - IBD nurses: a vital resource for patients and clinics.

PMID- 25062311
TI  - Enhancing nurse-patient communication: a critical reflection.
AB  - Patients with cancer can easily become overloaded with information about
      diagnosis, prognosis, treatments and side effects. One of a nurse's most
      important roles is to help patients and their families make sense of this,
      providing support and information through their cancer journey. However, many
      barriers exist, including the nurse's own knowledge limitations, time constraints
      and the patient's engagement with the nurse. This paper uses critical reflection
      to evaluate an incident from clinical practice involving a patient with prostate
      cancer suffering from a distressing side effect of treatment: urinary
      incontinence following a transurethral resection of the prostate (TURP). The
      paper examines nurse-patient communication, and evaluates how nurses can use
      communication strategies to minimise patient distress. Practical approaches to
      managing urinary incontinence are also discussed. This paper demonstrates that
      critical reflection is a valuable learning process that can alter clinical
      nursing practice to provide the best care for people with cancer. 

PMID- 25062312
TI  - Outcomes in non-surgical management for bowel dysfunction.
AB  - This retrospective review considers clinical outcomes of patients following non
      surgical management of bowel dysfunction (faecal incontinence and constipation),
      within a tertiary centre's pelvic floor unit. Between November 2010 and January
      2013, 443 patients were entered into a database and the results of their
      treatment were recorded. To capture the treatment modalities that patients
      received they were grouped into three categories: defaecatory techniques and/or
      pelvic floor exercises; dietary advice and/or medication recommendations; rectal
      irrigation or the use of anal plugs. Patients received a median number of three
      sessions with a specialist nurse or physiotherapist. After completing a programme
      of therapy, 81% of patients had an improved St Mark's incontinence score and 75%
      of patients had an improved Thompson's functional constipation score. Subjective
      symptom improvement was reported in 78% of patients. The majority of these
      patients were discharged in 2011 and 2012 and have not required follow-up,
      suggesting that non-surgical management is effective on a medium-term basis. 

PMID- 25062313
TI  - Preventing muscular contractures through routine stroke patient care.
AB  - The aim of this article is to elevate the standard of ward-based routine care by
      informing readers about the prevention and management of muscular contractures
      post-cerebrovascular accident (CVA). Musculoskeletal complications can develop at
      any time during the acute or latter stages of stroke care and rehabilitation;
      therefore, it is imperative that all nurses understand the importance of correct
      limb placement and some of the detrimental complications that can occur. By
      placing more onus on therapeutic positioning and earlier mobilisation, nurses,
      working alongside allied health professionals, can significantly improve
      morbidity-related outcomes. 

PMID- 25062314
TI  - Attending to the spiritual in dementia care nursing.
AB  - Spirituality is a complex and subjective concept. However, spiritual wellness is
      an important component in a person's overall well-being and the spiritual support
      of patients is central to nursing care. People with dementia may not be well
      supported in this aspect of care; this may lead to spiritual distress. Spiritual
      needs may be identified by taking the person's spiritual history or, in the case
      of advanced dementia, by asking a person's significant others about the important
      spiritual aspects of the person's life. Spiritual care for people with dementia
      involves reflective practice and meaningful engagement with the person with
      dementia, so as to facilitate shared understanding. Furthermore, the support of
      the spiritual and religious beliefs of the person need to be facilitated within
      an individualised or person centred approach to care and delivered within a multi
      disciplinary collaborative context.

PMID- 25062315
TI  - Spiritual coping of older people in Malta and Australia (part 1).
AB  - This descriptive sequential explanatory study, which forms part of a larger
      study, investigated the use of spiritual coping strategies by three cohort groups
      of Maltese older residents in three phases. The theoretical model of causal
      pathway for mental health based on monotheistic religions (Christianity, Judaism,
      and Islam) guided the study. Participants were recruited from four private homes:
      two in Australia (n=30), two in Malta (n=43) and two state residences also in
      Malta (n=64). The residents (n=137; men n=103, women n=34), mean (M) age 72.8
      years, were all Roman Catholics, mobile and with a minimum residence of 6 months.
      The quantitative data (phase I) were collected by the Maltese version of the
      Spiritual Coping Strategies scale ( Baldacchino and Buhagiar, 2003 ). The
      qualitative findings in phase II derived from the face-to-face interviews and
      focus groups explain the use of spiritual coping strategies and how they
      contributed toward coping with institutionalisation. Significant differences were
      found in spiritual coping (F=11.434; p=0.001; degree of freedom (df)=2) whereby
      the cohort in Australia scored the highest scores in the total spiritual coping
      (M=48.60; standard deviation (SD)=6.251), religious coping (M=23.47; SD=2.145)
      and existential coping (M=25.13; SD=6.033). No significant differences were found
      in the total spiritual coping between subgroups of mobility and demographic
      characteristics except by gender (Student's t-test (t)=2.455; p=0.015) whereby
      women (M=22.09; SD=4.325) scored higher than the men (M=19.67; SD=4.508).
      Australian private homes reported the highest (significant) mean scores in total
      spiritual coping, religious coping and existential coping. Recommendations were
      set for clinical practice and management, nursing education, and further
      research. 

PMID- 25062317
TI  - Psychological impact of cancer pain on patients and their quality of life.

PMID- 25062316
TI  - Sedation and its psychological effects following intensive care.
AB  - Significant psychological impacts, including post-traumatic stress disorder
      (PTSD), have been associated with patients under sedation in intensive care units
      (ICUs). However, it remains unknown if and how sedation is related to post-ICU
      psychological outcomes. This literature review explores the relationships between
      sedation, the depth of sedation and psychological disorders. A review of existing
      literature was undertaken systematically with key terms and included peer
      reviewed primary research and randomised controlled trials (RCTs). To ensure
      subject relevance pre-2006, non-English and paediatric-based research was
      excluded. Findings highlighted that reduced sedation levels did not significantly
      reduce the outcome of PTSD, yet reduced ICU length of stay and length of
      mechanical ventilation (MV) were both associated with lighter sedation. Further
      research is recommended into more specific factual and delusional memories post
      ICU in relation to the level of sedation and to psychological distress. 

PMID- 25062318
TI  - Tackling one thing at a time.

PMID- 25062319
TI  - User involvement: beyond the tick-box.

PMID- 25062320
TI  - Mental Capacity and Mental Health Acts part 1: advance decisions.
AB  - The Department of Health is undertaking a review of the Mental Health Act 1983
      code of practice and as part of that review has opened a consultation on what
      changes should be made. One key area for change is a chapter that provides
      clearer information about the interface between the Mental Health Act 1983 and
      the Mental Capacity Act 2005. Both the House of Commons Health Select Committee
      and the House of Lords Mental Capacity Act Committee have argued that poor
      understanding of the interface has led to flawed decision making by doctors and
      nurses. In the first of a short series of articles, Richard Griffith considers
      the interface between these two important statutes, beginning with advance
      decisions to refuse treatment (ADRT). 

PMID- 25062321
TI  - Promoting safety, honesty and openness in the NHS.

PMID- 25062322
TI  - End-of-life care: replacing the Liverpool Care Pathway.

PMID- 25062323
TI  - Reflection: from staff nurse to nurse consultant. Part 12: series summary.

PMID- 25062324
TI  - What's right with nursing?

PMID- 25062325
TI  - Highly selective and ultra fast solid-phase extraction of N-glycoproteome by
      oxime click chemistry using aminooxy-functionalized magnetic nanoparticles.
AB  - For the highly efficient extraction of the N-glycoproteome, a novel solid-phase
      extraction method based on oxime click chemistry has been developed. With the use
      of a newly synthesized aminooxy-functionalized magnetic nanoparticle, the
      oxidized glycan chains on glycopeptides readily react with the aminooxy groups
      through oxime click chemistry, resulting in the highly selective extraction of
      glycopeptides. Compared to the traditional hydrazide chemistry-based method,
      which takes 12-16 h of coupling time, this new method renders excellent
      enrichment performance within 1 h. Furthermore, the enrichment sensitivity (fmol
      level), selectivity (extracting glycopeptides from mixtures of nonglycopeptides
      at a 1:100 molar ratio), and reproducibility (CVs < 20%) are also dramatically
      improved. We have successfully profiled the N-glycoproteome from only 1 MUL of
      human colorectal cancer serum using this innovative protocol, which offers a more
      efficient alternative N-glycoproteome extraction method. 

PMID- 25062326
TI  - Coffee intake is associated with lower levels of oxidative DNA damage and
      decreasing body iron storage in healthy women.
AB  - Habitual coffee drinking has been linked to a lower risk for some forms of
      cancer, but the mechanism remains elusive. Coffee may decrease oxidative DNA
      damage, an important pathway to carcinogenesis. We examined the association
      between coffee consumption and urinary 8-hydroxydeoxyguanosine (8-OHdG)
      concentrations, a biomarker of systemic oxidative DNA damage and repair, in 507
      healthy subjects (298 men and 209 women aged 21-67 yr) while adjusting for age,
      sex, smoking status, body mass index, job type, and fasting blood glucose in
      multivariable regression models. The association with green tea consumption was
      also assessed. Urinary 8-OHdG concentrations tended to decrease with coffee
      consumption in women (trend P = 0.046), with women drinking 2-3 cups of coffee
      per day showing the lowest mean of urinary 8-OHdG concentrations. This
      association was largely attenuated after further adjustment for serum ferritin
      concentrations, a marker of body iron storage (trend P = 0.96). Green tea
      consumption was not associated with urinary 8-OHdG concentrations. Coffee
      drinking may be associated with decreased systemic oxidative DNA damage through
      decreasing body iron storage in women.

PMID- 25062328
TI  - Structural and mechanical characteristics of polymersomes.
AB  - Polymersomes self-assembled from amphiphilic macromolecules have attracted
      growing attention because of their multifunctionality and stability. By
      controlling the structural characteristics of polymersomes, including vesicle
      shape, size, and membrane thickness, their mechanical and transport properties as
      well as their fusion behavior can be manipulated. Numerous experimental
      techniques have been developed to explore polymersome characteristics; however,
      experimental microscopic observations and knowledge of vesicles are limited.
      Mesoscale simulations can complement experimental studies of the vesicular
      features at the microscopic level and thus provide a feasible method to better
      understand the relationship between the fundamental structures and
      physicochemical properties of polymersomes. Moreover, the predictive ability of
      the simulation approaches may greatly assist developments and future applications
      of polymersomes. 

PMID- 25062327
TI  - Real-time analysis of porphyrin J-aggregation on a plant-esterase-functionalized
      surface using quartz crystal microbalance with dissipation monitoring.
AB  - The J-aggregation of meso-tetra (4-sulfonatophenyl) porphine (TPPS4) on a plant
      esterase-functionalized surface in a 1:1 v/v mixture of 0.05 M HCl/ethanol (pH
      ~1.38) was analyzed in real time using a quartz crystal microbalance with
      dissipation monitoring (QCM-D). Simultaneous changes in frequency (Deltaf) and
      energy dissipation (DeltaD) correlated well with mass and structural changes
      during the sequential phases of slow nucleation, rapid aggregation, and
      equilibration in J-aggregation. The time-dependent mass adsorption could be
      quantitatively analyzed with a model, which integrated two simple equations
      obtained when the surface concentration of TPPS4 (Gamma(TPPS4)) was below and
      above the critical aggregation surface concentration (CASC). This study provides
      a new view for the protein-induced J-aggregation process, which may be helpful
      for understanding the interactions of self-assembled nanostructures with
      biomolecules.

PMID- 25062330
TI  - Improved Calibration of Voltammetric Sensors for Studying Pharmacological Effects
      on Dopamine Transporter Kinetics in Vivo.
AB  - The distribution and density of neurons within the brain poses many challenges
      when making quantitative measurements of neurotransmission in the extracellular
      space. A volume neurotransmitter is released into the synapse during chemical
      communication and must diffuse through the extracellular space to an implanted
      sensor for real-time in situ detection. Fast-scan cyclic voltammetry is an
      excellent technique for measuring biologically relevant concentration changes in
      vivo; however, the sensitivity is limited by mass-transport-limited adsorption.
      Due to the resistance to mass transfer in the brain, the response time of
      voltammetric sensors is increased, which decreases the sensitivity and the
      temporal fidelity of the measurement. Here, experimental results reveal how the
      tortuosity of the extracellular space affects the response of the electrode.
      Additionally, a model of mass-transport-limited adsorption is utilized to account
      for both the strength of adsorption and the magnitude of the diffusion
      coefficient to calculate the response time of the electrode. The response time is
      then used to determine the concentration of dopamine released in response to
      salient stimuli. We present the method of kinetic calibration of in vivo
      voltammetric data and apply the method to discern changes in the KM for the
      murine dopamine transporter. The KM increased from 0.32 +/- 0.08 MUM (n = 3
      animals) prior to drug administration to 2.72 +/- 0.37 MUM (n = 3 animals) after
      treatment with GBR-12909. 

PMID- 25062331
TI  - Discovery of small-molecule inhibitors selectively targeting the DNA-binding
      domain of the human androgen receptor.
AB  - The human androgen receptor (AR) is considered as a master regulator in the
      development and progression of prostate cancer (PCa). As resistance to clinically
      used anti-AR drugs remains a major challenge for the treatment of advanced PCa,
      there is a pressing need for new anti-AR therapeutic avenues. In this study, we
      identified a binding site on the DNA binding domain (DBD) of the receptor and
      utilized virtual screening to discover a set of micromolar hits for the target.
      Through further exploration of the most potent hit (1), a structural analogue (6)
      was identified demonstrating 10-fold improved anti-AR potency. Further
      optimization resulted in a more potent synthetic analogue (25) with anti-AR
      potency comparable to a newly FDA-approved drug Enzalutamide. Site-directed
      mutagenesis demonstrated that the developed inhibitors do interact with the
      intended target site. Importantly, the AR DBD inhibitors could effectively
      inhibit the growth of Enzalutamide-resistant cells as well as block the
      transcriptional activity of constitutively active AR splice variants, such as V7.

PMID- 25062332
TI  - Moesin expression in fibrosis in the mouse cornea after sterile mechanical trauma
      or infection.
AB  - PURPOSE: The aim of this study was to compare the expression patterns of 3
      important biochemical characteristics of fibrosis-moesin, transforming growth
      factor (TGF)-beta1, and alpha-smooth muscle actin (SMA) in the mouse cornea with
      fibrosis induced by common etiologies-sterile mechanical injury and infection.
      METHODS: Corneas of 8-week-old C57BL6 mice were either wounded after an anterior
      keratectomy or were infected by Pseudomonas aeruginosa, and the animals were
      killed on days 2 and 7, and on weeks 2 and 4 after the procedure. Western blot
      and immunofluorescence were used to analyze the expression of moesin and phospho
      moesin, and the presence of myofibroblasts identified by the expression of alpha
      SMA in the corneal stroma. The expression of TGF-beta1 was analyzed by
      immunofluorescence. RESULTS: By immunofluorescent analysis, TGF-beta1, alpha-SMA,
      and phospho-moesin were not detected in the normal corneal stroma. However, after
      either treatment, TGF-beta1 expression increased, along with phospho-moesin in
      the wounded corneal stroma until day 7, and decreased after week 2. No expression
      of TGF-beta1 and phospho-moesin was found at postoperative week 4. Moesin
      expression increased until week 2. Myofibroblasts positive for alpha-SMA were
      detected on day 2 until week 4 and peaked at week 2. Western blot analysis
      confirmed the immunofluorescent data for moesin, phospho-moesin, and alpha-SMA.
      CONCLUSIONS: The similar expression pattern of moesin, phospho-moesin, TGF-beta1,
      and alpha-SMA in the mouse cornea with fibrosis caused by sterile mechanical
      injury or infection indicated a role for moesin signaling in corneal fibrosis.
      Interference with the action of moesin may be a potential approach for
      intervention strategies to avert fibrosis after infection or mechanical injury.

PMID- 25062333
TI  - Progressive corneal clearance after a DMEK graft partially folded over on itself
      in a non-fuchs pseudophakic eye.
AB  - PURPOSE: The aim of this study was to report progressive corneal clearance and
      endothelial cell repopulation after a Descemet membrane endothelial keratoplasty
      graft that was partially folded over on itself in a pseudophakic patient without
      endothelial dystrophy. METHODS: Retrospective case report. RESULTS: A 75-year-old
      man without Fuchs dystrophy underwent cataract extraction on his right eye in
      2007, and 5 years later, Descemet membrane endothelial keratoplasty was performed
      for pseudophakic edema in the same eye at another center. On presentation at our
      institution, a graft that is partially folded over on itself was observed in the
      right eye, leaving about 2/3 of donor endothelium correctly exposed. The graft
      was only attached in the lower part of the cornea. We observed progressive
      clearance of the entire cornea within 7 months with reendothelialization of the
      entire cornea. Good visual acuity was achieved, with no evidence of recurrent
      corneal edema. CONCLUSIONS: Endothelial cell migration and repopulation in the
      presence of a folded attached endothelium graft may occur, resulting in corneal
      clearance and improved visual outcome. This could happen in patients with
      pseudophakic edema without congenital endothelial dystrophy.

PMID- 25062334
TI  - Herpes zoster stromal keratitis after varicella vaccine booster in a pediatric
      patient.
AB  - PURPOSE: In this study, the case of a healthy pediatric patient who presented
      with herpes zoster (HZ) stromal keratitis after vaccination with live attenuated
      varicella vaccine (Varivax) and subsequent booster is described. METHOD: This is
      a retrospective case review. RESULTS: A 6-year-old girl with no medical history
      presented with HZ ophthalmicus and stromal keratitis. She had received the
      original Varivax vaccine at 1 year of age and a booster 1 year before
      presentation. Topical prednisolone acetate was started with subsequent
      improvement in inflammation and visual acuity. However, the patient was unable to
      be completely tapered off the steroids because of reactivation. CONCLUSIONS: HZ
      ophthalmicus with stromal keratitis is a rare but potentially damaging
      manifestation of the varicella zoster virus in the pediatric population. Long
      term data regarding reactivation rates in the post-vaccination era are still
      limited. Close follow-up is needed to ensure resolution of the infiltrates, and
      reactivation may require long-term steroid therapy.

PMID- 25062335
TI  - Interface infection after descemet stripping automated endothelial keratoplasty:
      outcomes of therapeutic keratoplasty.
AB  - PURPOSE: The aim of this study was to evaluate the visual outcomes and graft
      survival rate after therapeutic keratoplasty performed for interface infection
      after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS:
      This is a retrospective, interventional case series. The study population
      comprised 7 patients who developed unilateral post-DSAEK interface infection
      unresponsive to conservative treatment, with or without graft exchange, and were
      treated with penetrating keratoplasty (PK), 9 to 9.5 mm in diameter, with en bloc
      excision of the recipient cornea and DSAEK graft. The main outcome measures
      included best spectacle-corrected visual acuity, refractive error, histological
      examination, reinfection, and rejection and graft survival rates. RESULTS:
      Interface infection was diagnosed in 10 (0.92%) of 1088 eyes that underwent DSAEK
      at our institution between 2005 and 2013. Seven of 10 eyes (0.64% of the total)
      were unresponsive to conservative treatment and underwent therapeutic
      keratoplasty. Candida and Staphylococcus species were identified in 3 cases each,
      and Nocardia species was identified in 1 case. With a mean post-PK follow-up of
      25.4 months (range 4-60 months), no recurrence of infection was seen in any eye,
      and 5 of 7 PK grafts remained clear. Best spectacle-corrected visual acuity was
      20/20 in 2 eyes, better than 20/50 in 4 eyes, and 20/100 or worse in 3 eyes, in 2
      of which the graft had failed within 1 year of performing the PK. CONCLUSIONS:
      Therapeutic keratoplasty is instrumental in eliminating interface infection after
      DSAEK, possibly leading to excellent visual outcomes with a relatively high graft
      survival rate.

PMID- 25062336
TI  - Randomized comparison of topical prednisolone acetate 1% versus fluorometholone
      0.1% in the first year after descemet membrane endothelial keratoplasty.
AB  - PURPOSE: The aim of this study was to compare the efficacy and side effects of
      prednisolone acetate 1% versus fluorometholone 0.1% after Descemet membrane
      endothelial keratoplasty (DMEK). METHODS: DMEK recipients used prednisolone
      acetate 1% for 1 month, and they were randomized to either prednisolone or
      fluorometholone for months 2 through 12. Dosing was 4 times daily in months 1 to
      3, thrice daily in month 4, twice daily in month 5, and once daily in months 6 to
      12. The main outcomes were immunologic rejection episodes and intraocular
      pressure (IOP) elevation (defined as >=24 mm Hg or >=10 mm Hg increase over the
      preoperative baseline level), assessed by the Kaplan-Meier survival analysis.
      RESULTS: The study included 325 eyes (99% were white, 96% had Fuchs dystrophy,
      and 9% had a previous glaucoma diagnosis). No eyes (0%) assigned to prednisolone
      versus 2 eyes (1.4%) assigned to fluorometholone experienced a possible (n = 1)
      or probable (n = 1) rejection episode (P = 0.17). Both rejection episodes
      resolved successfully with increased topical steroids. In the prednisolone arm, a
      significantly higher proportion exceeded the defined IOP elevation threshold (22%
      vs. 6%, P = 0.0005), and glaucoma medications were initiated or increased more
      often (17% vs. 5%, P = 0.0003). The most frequent reasons for discontinuing the
      assigned intervention were IOP management (n = 13 eyes assigned to prednisolone)
      or inflammation management (n = 3 eyes assigned to fluorometholone). One-year
      endothelial cell loss was comparable in both arms (30% vs. 31%, P = 0.50).
      CONCLUSIONS: DMEK has a remarkably low rejection episode rate (<1% through 1
      year), as confirmed in this prospective randomized study. This provides a unique
      opportunity to reduce postoperative topical corticosteroid strength and thereby
      reduce the risk of steroid-associated complications.

PMID- 25062337
TI  - Do it right the first time: advice for cornea authors.

PMID- 25062338
TI  - Prognostic indices of perioperative outcome following transperitoneal
      laparoscopic adrenalectomy.
AB  - OBJECTIVES: We sought to identify preoperative patient and tumor characteristics
      that may be useful prognostic indicators of postsurgical outcome in patients
      undergoing laparoscopic adrenalectomy (LA). SUBJECTS AND METHODS: Data from 92
      patients who underwent 93 transabdominal LA procedures between 2006-2012 were
      retrieved. Patients were stratified based on estimated blood loss (EBL), length
      of stay (LOS), and perioperative complications. Interdependencies between
      surgical outcome and patient demographics, tumor characteristics, comorbidities,
      and Charlson Comorbidity Index (CCI) were statistically analyzed. The predictive
      capacity of each index was assessed using receiver operating characteristic
      curves. RESULTS: Neither age, gender, tumor laterality, body mass index, American
      Society of Anesthesiologists (ASA) score, nor CCI predicted the occurrence of
      perioperative complications. EBL was significantly associated with increased age,
      tumor size, ASA score, and CCI, whereas prolonged LOS was associated with higher
      ASA score. Tumor size was related, although not significantly, to LOS and
      perioperative complications. Tumors >=7.5 cm in diameter were significantly
      associated with worse perioperative outcomes. CONCLUSIONS: LA for adrenal lesions
      demonstrated reasonable complication rates and perioperative outcomes. Tumor
      size, CCI, and ASA score are predictive of increased EBL and LOS.

PMID- 25062339
TI  - The incidence and risk of early postoperative small bowel obstruction after
      laparoscopic resection for colorectal cancer.
AB  - BACKGROUND: Early postoperative small bowel obstruction is associated with
      considerable morbidity and mortality but has not been well documented in the era
      of laparoscopic surgery for colorectal cancer. SUBJECTS AND METHODS: Consecutive
      patients who had undergone laparoscopic resection for colorectal cancer were
      studied. RESULTS: In total, 1787 patients (105 with and 1682 without early
      postoperative small bowel obstruction) with colorectal cancer requiring
      laparoscopic colorectal surgery were evaluated in this study. Ten patients (0.56%
      among the total patient population, 9.5% among patients who experienced early
      postoperative small bowel obstruction) who did not respond to conservative
      treatment for more than 14 days required surgical intervention. Multivariate
      analysis showed that male sex (adjusted odds ratio [AOR]=2.27), combined
      operation (AOR=2.23), and diverting stoma (AOR=4.79) were associated with a
      higher early postoperative small bowel obstruction rate. For factors related to
      surgical difficulty, open conversion (AOR=2.85), blood transfusion (AOR=3.51),
      and an operation time longer than 180 minutes (AOR=1.91) were independent factors
      associated with an increased early postoperative small bowel obstruction rate.
      CONCLUSIONS: Early postoperative small bowel obstruction following laparoscopic
      resection for colorectal cancer occurred in 5.9% of patients. Factors for
      predicting the development of early postoperative small bowel obstruction in
      patients with colorectal cancer are variables reflective of a more difficult
      surgery, rather than pathologic disease severity or anatomical location. In
      addition, most patients with early postoperative small bowel obstruction improved
      with conservative treatment, and surgical treatment was rarely needed.

PMID- 25062340
TI  - Robotic rectovesical fistula repair: a successful approach.
AB  - OBJECTIVE: To describe our technique of robotic rectovesical fistula (RVF) repair
      through the report of a case unique for its pathogenesis. RVF is a rare but
      devastating complication of prostatic surgery and can nowadays be managed with a
      minimally invasive approach. PATIENT AND METHODS: We describe in detail all the
      steps of our robotic RVF repair, performed on a 76-year-old man who developed RVF
      after radical prostatectomy. The RVF had been induced by tissue erosion due to
      Hem-o-lok((r)) (Teleflex Medical, Research Triangle Park, NC) clips and had been
      unsuccessfully treated with an over-the-scope clip. RESULTS: Our surgery was
      successful with an operative time of 70 minutes and an estimated blood loss of
      150 mL. The postoperative course was uneventful, and the patient was discharged
      on postoperative Day 3. CONCLUSIONS: Our technique of robotic RVF repair was safe
      and effective. Care must be taken when considering new, endoscopic devices for
      the cure of RVF. A prospective study with a long follow-up is advised to validate
      our results.

PMID- 25062341
TI  - Accessible laparoscopic instrument tracking ("InsTrac"): construct validity in a
      take-home box simulator.
AB  - INTRODUCTION: Objective performance feedback has potential to maximize the
      training benefit of laparoscopic simulators. Instrument movement metrics are,
      however, currently the preserve of complex and expensive systems. We aimed to
      develop and validate affordable, user-ready software that provides objective
      feedback by tracking instrument movement in a "take-home" laparoscopic simulator.
      MATERIALS AND METHODS: Computer-vision processing tracks the movement of colored
      bands placed around the distal instrument shafts. The position of each instrument
      is logged from the simulator camera feed and movement metrics calculated in real
      time. Ten novices (junior doctors) and 13 general surgery trainees (StR)
      (training years 3-7) performed a standardized task (threading string through
      hoops) on the eoSim (eoSurgicalTM Ltd., Edinburgh, Scotland, United Kingdom) take
      home laparoscopic simulator. Statistical analysis was performed using unpaired t
      tests with Welch's correction. RESULTS: The software was able to track the
      instrument tips reliably and effectively. Significant differences between the two
      groups were observed in time to complete task (StR versus novice, 2 minutes 33
      seconds versus 9 minutes 53 seconds; P=.01), total distance traveled by
      instruments (3.29 m versus 11.38 m, respectively; P=.01), average instrument
      motion smoothness (0.15 mm/second(3) versus 0.06 mm/second(3), respectively;
      P<.01), and handedness (mean difference between dominant and nondominant hand)
      (0.55 m versus 2.43 m, respectively; P=.03). There was no significant difference
      seen in the distance between instrument tips, acceleration, speed of instruments,
      or time off-screen. CONCLUSIONS: We have developed software that brings objective
      performance feedback to the portable laparoscopic box simulator. Construct
      validity has been demonstrated. Removing the need for additional motion-tracking
      hardware makes it affordable and accessible. It is user-ready and has the
      potential to enhance the training benefit of portable simulators both in the
      workplace and at home.

PMID- 25062343
TI  - An autopsy case of sudden unexpected death due to a glial cyst of the pineal
      gland.
AB  - Pineal cysts are usually asymptomatic; however, they may rarely cause symptoms
      such as chronic headache, paroxysmal headache with gaze paresis, postural
      syncope, loss of consciousness, and sudden death. A 30-year-old woman with no
      specific medical history except chronic headache was found collapsed in a public
      toilet per se. Postmortem examination revealed no external injuries or internal
      diseases except a cystic lesion of the pineal gland. Histologic examination
      showed an internal cyst surrounded by glial tissues and pineal parenchyma that
      was diagnosed as a glial cyst of the pineal gland. Although the pineal cyst
      cannot be confirmed as the cause of death, it was considered, as no other cause
      was evident. Herein, we report a pineal cyst considered as an assumed cause of
      death. 

PMID- 25062342
TI  - Cosmetic outcomes following appendectomy in children: a comparison of surgical
      techniques.
AB  - BACKGROUND: Although cosmetic superiority is widely stated as an advantage of
      single-incision laparoscopy, there are limited studies looking at cosmetic
      outcome. We sought to determine patients' cosmetic satisfaction after undergoing
      appendectomy by the single-incision laparoscopic appendectomy (SILA), multiport
      laparoscopic appendectomy (LA), or open appendectomy (OA) procedure. PATIENTS AND
      METHODS: Five hundred eighty pediatric patients who underwent appendectomy at a
      single institution between February 2010 and July 2011 were identified and asked
      to complete the Patient Scar Assessment Scale (PSAS), a validated evaluation tool
      for linear scars. In addition, patients were asked the "Ultimate Question" (UQ),
      which correlates with a patient's overall satisfaction. Linear regression models
      were used to examine differences between surgical approaches with statistical
      significance set at P<.05. Covariates for all models included patient
      demographics, length of stay, and surgeon. RESULTS: In total, 212 surveys were
      returned (SILA, 122; LA, 41; OA, 49) for a response rate of 37%. Regression
      models demonstrated significantly higher mean total PSAS scores for patients who
      underwent SILA and laparoscopic appendectomy (LA) appendectomy procedures
      compared with the open procedure (SILA, 8.70; LA, 8.86; OA, 8.01; beta=-0.21,
      P<.05). Patients who experienced the SILA and LA procedures reported
      significantly higher mean UQ scores compared with OA (SILA, 9.79; LA, 9.75; OA,
      9.39; beta=-0.22, P<.05). SILA patients reported a 10 on the UQ significantly
      more often (91.1%) compared with either LA (81%) or OA (75.5%) (P<.05).
      CONCLUSIONS: SILA or LA appendectomy was associated with significantly increased
      cosmetic satisfaction by patients and their families when compared with OA. This
      is the first study to show that pediatric patients value attempts to minimize
      scarring with laparoscopic surgery. Further studies are needed to determine if
      specific patient factors influence satisfaction with scars.

PMID- 25062344
TI  - Novel solvates M(BH4)3S(CH3)2 and properties of halide-free M(BH4)3 (M = Y or
      Gd).
AB  - Rare earth metal borohydrides have been proposed as materials for solid-state
      hydrogen storage because of their reasonably low temperature of decomposition.
      New synthesis methods, which provide halide-free yttrium and gadolinium
      borohydride, are presented using dimethyl sulfide and new solvates as
      intermediates. The solvates M(BH4)3S(CH3)2 (M = Y or Gd) are transformed to alpha
      Y(BH4)3 or Gd(BH4)3 at ~140  degrees C as verified by thermal analysis. The
      monoclinic structure of Y(BH4)3S(CH3)2, space group P21/c, a = 5.52621(8), b =
      22.3255(3), c = 8.0626(1) A and beta = 100.408(1) degrees , is solved from
      synchrotron radiation powder X-ray diffraction data and consists of buckled
      layers of slightly distorted octahedrons of yttrium atoms coordinated to five
      borohydride groups and one dimethyl sulfide group. Significant hydrogen loss is
      observed from Y(BH4)3 below 300  degrees C and rehydrogenation at 300  degrees C
      and p(H2) = 1550 bar does not result in the reformation of Y(BH4)3, but instead
      yields YH3. Moreover, composites systems Y(BH4)3-LiBH4 1 : 1 and Y(BH4)3-LiCl 1 :
      1 prepared from as-synthesised Y(BH4)3 are shown to melt at 190 and 220  degrees
      C, respectively.

PMID- 25062346
TI  - Predictive medicine, pathophysiology and therapeutics.

PMID- 25062345
TI  - Rapid detection of atrazine and metolachlor in farm soils: gas chromatography
      mass spectrometry-based analysis using the bubble-in-drop single drop
      microextraction enrichment method.
AB  - Tracking of metolachlor and atrazine herbicides in agricultural soils, from
      spraying through to harvest, was conducted using our recently reported "bubble-in
      drop single-drop microextraction" method. The method showed good linearity (R(2)
      = 0.999 and 0.999) in the concentration range of 0.01-1.0 ng/mL with LOD values
      of 0.01 and 0.02 ng/mL for atrazine and metolachlor, respectively. Sonication
      methods were poor at releasing these herbicides from the soil matrixes, while hot
      water extraction readily liberated them, providing an efficient accessible
      alternative to sonication techniques. Good recoveries of 97% and 105% were shown
      for atrazine and metolachlor, respectively, from the soil. The spiking protocol
      was also investigated, resulting in a traceless spiking method. We demonstrate a
      very sensitive technique by which to assess, for example, the length of residence
      of pesticides in given soils and thus risk of exposure. 

PMID- 25062347
TI  - In memoriam: Mr. Donald Nixon Ross October 4, 1922 to July 7, 2014.

PMID- 25062348
TI  - Overexpression of Shox2 leads to congenital dysplasia of the temporomandibular
      joint in mice.
AB  - Our previous study reported that inactivation of Shox2 led to dysplasia and
      ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with
      human Shox partially rescued the phenotype with a prematurely worn out articular
      disc. However, the mechanisms of Shox2 activity in TMJ development remain to be
      elucidated. In this study, we investigated the molecular and cellular basis for
      the congenital dysplasia of TMJ in Wnt1-Cre; pMes-stop Shox2 mice. We found that
      condyle and glenoid fossa dysplasia occurs primarily in the second week after the
      birth. The dysplastic TMJ of Wnt1-Cre; pMes-stop Shox2 mice exhibits a loss of
      Collagen type I, Collagen type II, Ihh and Gli2. In situ zymography and
      immunohistochemistry further demonstrate an up-regulation of matrix
      metalloproteinases (MMPs), MMP9 and MMP13, accompanied by a significantly
      increased cell apoptosis. In addition, the cell proliferation and expressions of
      Sox9, Runx2 and Ihh are no different in the embryonic TMJ between the wild type
      and mutant mice. Our results show that overexpression of Shox2 leads to the loss
      of extracellular matrix and the increase of cell apoptosis in TMJ dysplasia by up
      regulating MMPs and down-regulating the Ihh signaling pathway. 

PMID- 25062350
TI  - Antibodies against West Nile and Shuni Viruses in Veterinarians, South Africa.

PMID- 25062349
TI  - Potential spermatogenesis recovery with bone marrow mesenchymal stem cells in an
      azoospermic rat model.
AB  - Non-obstructive azoospermia is the most challenging type of male infertility.
      Stem cell based therapy provides the potential to enhance the recovery of
      spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem
      cells (BMSCs) possess the potential to differentiate or trans-differentiate into
      multi-lineage cells, secrete paracrine factors to recruit the resident stem cells
      to participate in tissue regeneration, or fuse with the local cells in the
      affected region. In this study, we tested whether spermatogenically-induced BMSCs
      can restore spermatogenesis after administration of an anticancer drug.
      Allogeneic BMSCs were co-cultured in conditioned media derived from cultured
      testicular Sertoli cells in vitro, and then induced stem cells were transplanted
      into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8
      weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and
      protein markers, and after implantation the donor cells survived and located at
      the basement membranes of the recipient seminiferous tubules, in accordance with
      what are considered the unique biological characteristics of spermatogenic stem
      cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa,
      Stella, SMAD1, Dazl, GCNF, HSP90alpha, integrinbeta1, and c-kit) were expressed
      in the recipient testis tissue. No tumor mass, immune response, or inflammatory
      reaction developed. In conclusion, BMSCs might provide the potential to trans
      differentiate into spermatogenic-like-cells, enhancing endogenous fertility
      recovery. The present study indicates that BMSCs might offer alternative
      treatment for the patients with azoospermatic infertility after cancer
      chemotherapy. 

PMID- 25062351
TI  - Natural intrauterine infection with Schmallenberg virus in malformed newborn
      calves.
AB  - We surveyed morphologic alterations in calves in Belgium that were naturally
      infected in utero by Schmallenberg virus (SBV) and born with deformities during
      January-March 2012. SBV-specific RNA was distributed unevenly in different
      tissues. Natural intrauterine SBV infection of calves might cause serious damage
      to the central nervous system and muscles. 

PMID- 25062352
TI  - Nurse-police coalition: improves safety in acute psychiatric hospital.
AB  - Although police officers protect and secure the safety of citizens everywhere,
      nurses are the primary guardians of patient safety within the treatment milieu.
      At New Hampshire Hospital, both nurses and police officers share ownership of
      this responsibility, depending on the needs that arise specific to each
      profession. Psychiatric nurses take pride in their ability to de-escalate
      agitated and potentially aggressive patients; however, times arise when the best
      efforts of nurses fail, or when a situation requires intervention from police
      officers. Nurses and police officers at New Hampshire Hospital have worked
      together for many years to develop a trusting, respectful alliance. This
      coalition has resulted in a safe, clear, orderly process for transfer of
      authority from nurses to police during violent, clinically unmanageable
      psychiatric emergencies. Nurses and police officers work collaboratively toward
      the common goal of ensuring safety for patients and staff, while also
      acknowledging the unique strengths of each profession.

PMID- 25062353
TI  - Use of technology to enhance mental health for older adults.
AB  - Recent research suggests that older adults may gain significant mental health
      benefits from health resources made available through emerging modern
      technologies, especially because this population is becoming more Internet savvy.
      Technology-enhanced interventions for older adults have been shown to be helpful
      not only for general wellness activities (i.e., exercise), but also to
      specifically enhance mental health. This article focuses on two types of
      interventions for mental health: (a) cognitive-behavioral therapy for depression
      and anxiety and (b) assistive technology for individuals with dementia. Nurses
      should reevaluate their assumptions that older adults fear technology and explore
      whether different types of modern technology might be effective in enhancing
      mental health for these clients.

PMID- 25062354
TI  - Characterization of the symbiont Rickettsia in the mirid bug Nesidiocoris tenuis
      (Reuter) (Heteroptera: Miridae).
AB  - Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae) is an omnivorous insect used
      for biological control. Augmentative release and conservation of N. tenuis have
      been used for pest control in tomato crops. Intracellular bacterial symbionts of
      arthropods are common in nature and have diverse effects on their hosts; in some
      cases they can dramatically affect biological control. Fingerprinting methods
      showed that the symbiotic complex associated with N. tenuis includes Wolbachia
      and Rickettsia. Rickettsia of N. tenuis was further characterized by sequencing
      the 16S rRNA and gltA bacterial genes, measuring its amount in different
      developmental stages of the insect by real-time polymerase chain reaction, and
      localizing the bacteria in the insect's body by fluorescence in situ
      hybridization. The Rickettsia in N. tenuis exhibited 99 and 96% similarity of
      both sequenced genes to Rickettsia bellii and Rickettsia reported from Bemisia
      tabaci, respectively. The highest amount of Rickettsia was measured in the 5th
      instar and adult, and the symbionts could be detected in the host gut and
      ovaries. Although the role played by Rickettsia in the biology of N. tenuis is
      currently unknown, their high amount in the adults and localization in the gut
      suggest that they may have a nutritional role in this insect. 

PMID- 25062355
TI  - Exotic reaction front migration and stage structure in lithiated silicon
      nanowires.
AB  - Nanostructured silicon anodes, which possess extremely high energy density and
      accommodate large strain without pulverization, have been developed rapidly for
      high-power lithium ion batteries. Here, using in situ transmission electron
      microscopy, the lithiation behavior of silicon nanowires with diameters smaller
      than 60 nm was investigated. The study demonstrated a direct dependence of the
      self-limiting lithiation on the pristine diameter. A "punch-through" lithiation
      process at the core of nanowires with pristine diameters slightly larger than the
      self-limiting threshold is suggested to occur with the consequent formation of a
      stage structure. Our work demonstrates the crucial role of mechanical stress and
      local defects in determining the migration and geometry of the reaction front at
      the mesoscopic scale. This intriguing finding holds critical significance for the
      application of silicon nanostructures in high-power lithium ion batteries. 

PMID- 25062356
TI  - Food self-sufficiency across scales: how local can we go?
AB  - This study explores the potential for regions to shift to a local food supply
      using food self-sufficiency (FSS) as an indicator. We considered a region food
      self-sufficient when its total calorie production is enough to meet its demand.
      For future scenarios, we considered population growth, dietary changes, improved
      feed conversion efficiency, climate change, and crop yield increments. Starting
      at the 5' resolution, we investigated FSS from the lowest administrative levels
      to continents. Globally, about 1.9 billion people are self-sufficient within
      their 5' grid, while about 1 billion people from Asia and Africa require cross
      continental agricultural trade in 2000. By closing yield gaps, these regions can
      achieve FSS, which also reduces international trade and increases a self
      sufficient population in a 5' grid to 2.9 billion. The number of people depending
      on international trade will vary between 1.5 and 6 billion by 2050. Climate
      change may increase the need for international agricultural trade by 4% to 16%. 

PMID- 25062357
TI  - A comparison between brand-specific and traditional alcohol surveillance methods
      to assess underage drinkers' reported alcohol use.
AB  - BACKGROUND: Adolescent alcohol consumption remains common and is associated with
      many negative health outcomes. Unfortunately, common alcohol surveillance methods
      often underestimate consumption. Improved alcohol use measures are needed to
      characterize the landscape of youth drinking. OBJECTIVES: We aimed to compare a
      standard quantity-frequency measure of youth alcohol consumption to a novel brand
      specific measure. METHODS: We recruited a sample of 1031 respondents across the
      United States to complete an online survey. Analyses included 833 male and female
      underage drinkers ages 13-20. Respondents reported on how many of the past 30
      days they consumed alcohol, and the number of drinks consumed on an average
      drinking day. Using our brand-specific measure, respondents identified which
      brands they consumed, how many days they consumed each brand, and how many drinks
      per brand they usually had. RESULTS: Youth reported consuming significantly more
      alcohol (on average, 11 drinks more per month) when responding to the brand
      specific versus the standard measure (p < 0.001). The two major predictors of the
      difference between the two measures were being a heavy episodic drinker (p <
      0.001, 95% CI = 4.1-12.0) and the total number of brands consumed (p < 0.001, 95%
      CI = 2.0-2.8). CONCLUSION: This study contributes to the field of alcohol and
      adolescent research first by investigating a potentially more accurate alcohol
      surveillance method, and secondly by promoting the assessment of alcohol use
      among adolescents vulnerable to risky alcohol use. Finally, our survey addresses
      the potential impact of alcohol marketing on youth and their subsequent alcohol
      brand preferences and consumption.

PMID- 25062358
TI  - Potential of a renin inhibitory peptide from the red seaweed Palmaria palmata as
      a functional food ingredient following confirmation and characterization of a
      hypotensive effect in spontaneously hypertensive rats.
AB  - This work examined the resistance of the renin inhibitory, tridecapeptide
      IRLIIVLMPILMA derived previously from a Palmaria palmata papain hydrolysate,
      during gastrointestinal (GI) transit. Following simulated GI digestion, breakdown
      products were identified using mass spectrometry analysis and the known renin and
      angiotensin I converting enzyme inhibitory dipeptide IR was identified. In vivo
      animal studies using spontaneously hypertensive rats (SHRs) were used to confirm
      the antihypertensive effects of both the tridecapeptide IRLIIVLMPILMA and the
      seaweed protein hydrolysate from which this peptide was isolated. After 24 h, the
      SHR group fed the P. palmata protein hydrolysate recorded a drop of 34 mm Hg in
      systolic blood pressure (SBP) from 187 (+/-0.25) to 153 (+/- 0.64) mm Hg SBP,
      while the group fed the tridecapeptide IRLIIVLMPLIMA presented a drop of 33 mm Hg
      in blood pressure from 187 (+/-0.95) to 154 (+/-0.94) mm Hg SBP compared to the
      SBP recorded at time zero. The results of this study indicate that the seaweed
      protein derived hydrolysate has potential for use as antihypertensive agents and
      that the tridecapeptide is cleaved and activated to the dipeptide IR when it
      travels through the GI tract. Both the hydrolysate and peptide reduced SHR blood
      pressure when administered orally over a 24 h period. 

PMID- 25062359
TI  - Electrochemical control of cell and tissue polarity.
AB  - Localized ion fluxes at the plasma membrane provide electrochemical gradients at
      the cell surface that contribute to cell polarization, migration, and division.
      Ion transporters, local pH gradients, membrane potential, and organization are
      emerging as important factors in cell polarization mechanisms. The power of
      electrochemical effects is illustrated by the ability of exogenous electric
      fields to redirect polarization in cells ranging from bacteria, fungi, and
      amoebas to keratocytes and neurons. Electric fields normally surround cells and
      tissues and thus have been proposed to guide cell polarity in development,
      cancer, and wound healing. Recent studies on electric field responses in model
      systems and development of new biosensors provide new avenues to dissect
      molecular mechanisms. Here, we review recent advances that bring molecular
      understanding of how electrochemistry contributes to cell polarity in various
      contexts. 

PMID- 25062360
TI  - Cadherin adhesion and mechanotransduction.
AB  - Cadherins are the principal adhesion proteins at intercellular junctions and
      function as the biochemical Velcro that binds cells together. Besides this
      mechanical function, cadherin complexes are also mechanotransducers that sense
      changes in tension and trigger adaptive reinforcement of intercellular junctions.
      The assembly and regulation of cadherin adhesions are central to their mechanical
      functions, and new evidence is presented for a comprehensive model of cadherin
      adhesion, which is surprisingly more complex than previously appreciated. Recent
      findings also shed new light on mechanisms that regulate cadherin junction
      assembly, adhesion, and mechanotransduction. We further describe recent evidence
      for cadherin-based mechanotransduction, and the rudiments of the molecular
      mechanism, which involves alpha-catenin and vinculin as key elements. Potential
      roles of a broader cast of possible force-sensitive partners are considered, as
      well as known and speculative biological consequences of adhesion and force
      transduction at cadherin-mediated junctions. 

PMID- 25062361
TI  - The rhomboid-like superfamily: molecular mechanisms and biological roles.
AB  - The rhomboid proteases were first discovered as regulators of Drosophila EGF
      receptor signaling; soon after, it was recognized that they represented the
      founder members of a widespread family of intramembrane serine proteases
      conserved in all kingdoms. More recently still, the family was promoted to a
      superfamily, encompassing a wide variety of distantly related proteins. One of
      the surprises has been that many members of the rhomboid-like superfamily are not
      active proteases. Given the size of this clan, and its relatively recent
      discovery, there is still much to learn. Nevertheless, we already understand much
      about how rhomboid proteases perform their surprising function of cleaving
      transmembrane domains. We also already know that members of the rhomboid-like
      superfamily participate in biological functions as diverse as growth factor
      signaling, mitochondrial dynamics, inflammation, parasite invasion, and the
      machinery of protein quality control. Their potential medical significance is now
      becoming apparent in several areas. 

PMID- 25062365
TI  - Intercalation anode material for lithium ion battery based on molybdenum dioxide.
AB  - MoO2 is one of the most studied anode systems in lithium ion batteries.
      Previously, the reaction of MoO2 with lithium via conversion reaction has been
      widely studied. The present study highlights the possible application of MoO2 as
      an intercalation-based anode material to improve the safety of lithium ion
      batteries. Nanobelts of MoO2 are prepared by reduction of MoO3 nanobelts under
      hydrogen atmosphere. The intercalation behavior of MoO2 is specially focused upon
      by limiting the charge-discharge cycling to narrow potential window of 1.0 to 2.2
      V vs Li/Li(+) to avoid conversion reaction. An excellent electrochemical
      stability over 200 cycles is achieved at a current rate of 100 mAh g(-1). A phase
      transformation from monoclinic to orthorhombic to monoclinic is observed during
      the lithiation process, which is reversible during delithiation process and is
      confirmed by ex-situ XRD and electrochemical impedance spectroscopy. To further
      demonstrate the viability of MoO2 as a commercial anode material, MoO2 is tested
      in a full-cell configuration against LiFePO4. The full-cell assembly is cycled
      for 100 cycles and stable performance is observed. The combination showed an
      energy density of 70 Wh kg(-1) after 100 cycles. 

PMID- 25062363
TI  - Prenatal organochlorine and methylmercury exposure and memory and learning in
      school-age children in communities near the New Bedford Harbor Superfund site,
      Massachusetts.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs), organochlorine pesticides, and
      methylmercury (MeHg) are environmentally persistent with adverse effects on
      neurodevelopment. However, especially among populations with commonly experienced
      low levels of exposure, research on neurodevelopmental effects of these toxicants
      has produced conflicting results. OBJECTIVES: We assessed the association of low
      level prenatal exposure to these contaminants with memory and learning. METHODS:
      We studied 393 children, born between 1993 and 1998 to mothers residing near a
      PCB-contaminated harbor in New Bedford, Massachusetts. Cord serum PCB, DDE
      (dichlorodiphenyldichloroethylene), and maternal peripartum hair mercury (Hg)
      levels were measured to estimate prenatal exposure. Memory and learning were
      assessed at 8 years of age (range, 7-11 years) using the Wide Range Assessment of
      Memory and Learning (WRAML), age-standardized to a mean +/- SD of 100 +/- 15.
      Associations with each WRAML index-Visual Memory, Verbal Memory, and Learning
      were examined with multivariable linear regression, controlling for potential
      confounders. RESULTS: Although cord serum PCB levels were low (sum of four PCBs:
      mean, 0.3 ng/g serum; range, 0.01-4.4), hair Hg levels were typical of the U.S.
      fish-eating population (mean, 0.6 MUg/g; range, 0.3-5.1). In multivariable
      models, each microgram per gram increase in hair Hg was associated with, on
      average, decrements of -2.8 on Visual Memory (95% CI: -5.0, -0.6, p = 0.01), -2.2
      on Learning (95% CI: -4.6, 0.2, p = 0.08), and -1.7 on Verbal Memory (95% CI: 
      3.9, 0.6, p = 0.14). There were no significant adverse associations of PCBs or
      DDE with WRAML indices. CONCLUSIONS: These results support an adverse
      relationship between low-level prenatal MeHg exposure and childhood memory and
      learning, particularly visual memory.

PMID- 25062362
TI  - Insights into morphology and disease from the dog genome project.
AB  - Although most modern dog breeds are less than 200 years old, the symbiosis
      between man and dog is ancient. Since prehistoric times, repeated selection
      events have transformed the wolf into man's guardians, laborers, athletes, and
      companions. The rapid transformation from pack predator to loyal companion is a
      feat that is arguably unique among domesticated animals. How this transformation
      came to pass remained a biological mystery until recently: Within the past
      decade, the deployment of genomic approaches to study population structure,
      detect signatures of selection, and identify genetic variants that underlie
      canine phenotypes is ushering into focus novel biological mechanisms that make
      dogs remarkable. Ironically, the very practices responsible for breed formation
      also spurned morbidity; today, many diseases are correlated with breed identity.
      In this review, we discuss man's best friend in the context of a genetic model to
      understand paradigms of heritable phenotypes, both desirable and disadvantageous.

PMID- 25062364
TI  - Transmission of methicillin-resistant Staphylococcus aureus CC398 from livestock
      veterinarians to their household members.
AB  - There are indications that livestock-associated MRSA CC398 has a reduced human-to
      human transmissibility, limiting its impact on public health and justifying
      modified control measures. This study determined the transmissibility of MRSA
      CC398 from livestock veterinarians to their household members in the community as
      compared to MRSA non-CC398 strains. A one-year prospective cohort study was
      performed to determine the presence of MRSA CC398 in four-monthly nasal and
      oropharyngeal samples of livestock veterinarians (n  =  137) and their household
      members (n  =  389). In addition, a cross-sectional survey was performed to
      detect the presence of MRSA non-CC398 in hospital derived control patients (n  = 
      20) and their household members (n  =  41). Staphylococcus aureus isolates were
      genotyped by staphylococcal protein A (spa) typing and multiple-locus variable
      number tandem repeat analysis (MLVA). Mean MRSA CC398 prevalence over the study
      period was 44% (range 41.6-46.0%) in veterinarians and 4.0% (range 2.8-4.7%) in
      their household members. The MRSA CC398 prevalence in household members of
      veterinarians was significantly lower than the MRSA non-CC398 prevalence in
      household members of control patients (PRR 6.0; 95% CI 2.4-15.5), indicating the
      reduced transmissibility of MRSA CC398. The impact of MRSA CC398 appears to be
      low at the moment. However, careful monitoring of the human-to-human
      transmissibility of MRSA CC398 remains important. 

PMID- 25062369
TI  - Evidence-based practice requires research and data.

PMID- 25062373
TI  - WoCoVA 2014: sharing best practice.
AB  - The Berlin Congress Centre filled up from 18-20 June 2014 with IV professionals
      from around the world for the 3rd World Congress on Vascular Access. The theme of
      the Congress this year was about how to achieve safe and cost-effective venous
      access in every patient. Julie Smith, Editor of BJN, reports the highlights of
      the Congress below and emphasises the importance of sharing best practice in IV
      therapy. 

PMID- 25062374
TI  - A century of pathologising grief and bereavement.

PMID- 25062375
TI  - Health-promoting palliative care: a Scottish perspective.

PMID- 25062376
TI  - The implications of mandatory do not attempt cardiopulmonary resuscitation
      discussions.

PMID- 25062377
TI  - Compassionate paternalism and the Janet Tracey judgment.

PMID- 25062378
TI  - Palliative care staff's perceptions of do not attempt cardiopulmonary
      resuscitation discussions.
AB  - BACKGROUND: Do not attempt cardiopulmonary resuscitation (DNACPR) decisions aim
      to prevent unwanted and/or clinically inappropriate CPR attempts. As the NHS
      Scotland DNACPR policy has become embedded into clinical practice there has been
      greater awareness of the need to discuss DNACPR decisions with patients who would
      not benefit from CPR; however, little is known about how nursing and medical
      staff experience these discussions. AIM: This study aimed to explore clinician
      experiences of discussing DNACPR decisions with patients in a Scottish specialist
      palliative care inpatient and community setting. METHOD: Semi-structured face-to
      face interviews were held with 11 specialist palliative care clinicians. These
      were transcribed and thematic analysis was undertaken. RESULTS: The clinicians
      found DNACPR discussions challenging and experienced anxiety before discussions
      took place. They found it most appropriate to discuss DNACPR in the context of
      wider end-of-life discussions and in response to patient triggers. Patient
      clinician relationships were complex and could make the conversation easier or
      more difficult. Negative patient reactions were rare and discussions were thought
      to provide some patients with a sense of relief. CONCLUSION: The clinicians
      reported finding DNACPR discussions worthwhile and that they continue to discuss
      DNACPR decisions with patients despite the challenges. Recommendations for
      discussing DNACPR with patients are outlined.

PMID- 25062379
TI  - 'Cancer changes everything!' Exploring the lived experiences of women with
      metastatic breast cancer.
AB  - STUDY PURPOSE: The aim of this study was to further explore the lived experiences
      of women with metastatic breast cancer (MBC), to inform the development of
      interventions to enhance survivorship care for women with advanced disease.
      METHODOLOGY: Four semi-structured focus groups were conducted with women with
      MBC. The data was analysed using qualitative content analysis. RESULTS:
      Participants described the challenges of living with uncertainty, as a result of
      a lack of information regarding treatment options and symptom management, and a
      sense of the unknown related to prognosis and survival. Of major concern were
      changes in role functioning, altered relationships, and self-image. CONCLUSION:
      Women with metastatic breast cancer must cope with dramatic changes in all
      aspects of their lives. Clinicians should tailor survivorship care and evidence
      based interventions to individuals' concerns with changes in role functioning,
      fatigue, relationships, and self-image. A multidisciplinary approach should be
      used to address practical and existential concerns focused on improving quality
      of life.

PMID- 25062380
TI  - Work engagement and attitudes toward caring for dying patients and families among
      home-visiting nurses in Japan.
AB  - BACKGROUND: Nurses with higher levels of work engagement tend to be highly
      efficient in their work and more willing to keep working and to provide patient
      centred care. However, whether more engaged nurses provide end-of-life care more
      proactively has not been examined in the home-care setting. AIM: This study aimed
      to examine work engagement among home-visiting nurses in Japan and its
      relationship with their attitudes toward caring for dying patients and their
      families. METHODS: A total of 343 nurses working in 62 agencies across Chiba
      prefecture, eastern Japan, received an anonymous self-administered questionnaire
      from July to August 2012. The authors performed multiple regression analysis to
      explore the relationships between home-visiting nurses' work engagement and
      attitudes. RESULTS: Data from 184 nurses (53.6%) was analysed. Work engagement
      was significantly positively related to the nurses' attitudes toward caring for
      dying patients and their families. CONCLUSION: As more engaged nurses tend to
      have more positive attitudes toward caring for dying patients and their families,
      further research is needed to identify the factors that might help nursing
      managers to enhance their staff's engagement and perhaps thereby improve their
      attitudes, with the ultimate aim of achieving better outcomes for patients and
      families.

PMID- 25062381
TI  - Supporting service change in palliative care: a framework approach.
AB  - BACKGROUND: Palliative care services are increasingly identifying areas for
      improvement, then trying to create appropriate changes in response. Nurses in
      particular are often expected to take leading roles in quality improvement (QI)
      but are not necessarily trained or supported in these processes. METHODS: A
      framework approach to change was developed to guide services through a change
      cycle and delivered via workshops by representatives of three Australian national
      projects. Participants were predominantly nurses (80%), with the majority (63.7%)
      over the age of 50. FINDINGS: The workshops and the framework were positively
      evaluated, with participants feeling confident in a number of QI-related
      activities following workshop training. CONCLUSION: Recognising and addressing
      problems in clinical practice and service delivery is an important way for nurses
      to ensure quality care for patients; however, they need support in developing the
      skills and knowledge that are essential to successful QI activities.

PMID- 25062382
TI  - Reflections on the introduction of the Palliative Performance Scale (PPS) to NHS
      Grampian: 5 years on.

PMID- 25062384
TI  - Politics and palliative care: Panama.
AB  - Dion Smyth's review of the internet for palliative nursing. 

PMID- 25062385
TI  - Analysis of lipid phase behavior and protein conformational changes in
      nanolipoprotein particles upon entrapment in sol-gel-derived silica.
AB  - The entrapment of nanolipoprotein particles (NLPs) and liposomes in transparent,
      nanoporous silica gel derived from the precursor tetramethylorthosilicate was
      investigated. NLPs are discoidal patches of lipid bilayer that are belted by
      amphiphilic scaffold proteins and have an average thickness of 5 nm. The NLPs in
      this work had a diameter of roughly 15 nm and utilized membrane scaffold protein
      (MSP), a genetically altered variant of apolipoprotein A-I. Liposomes have
      previously been examined inside of silica sol-gels and have been shown to exhibit
      instability. This is attributed to their size (~150 nm) and altered structure and
      constrained lipid dynamics upon entrapment within the nanometer-scale pores (5-50
      nm) of the silica gel. By contrast, the dimensional match of NLPs with the
      intrinsic pore sizes of silica gel opens the possibility for their entrapment
      without disruption. Here we demonstrate that NLPs are more compatible with the
      nanometer-scale size of the porous environment by analysis of lipid phase
      behavior via fluorescence anisotropy and analysis of scaffold protein secondary
      structure via circular dichroism spectroscopy. Our results showed that the lipid
      phase behavior of NLPs entrapped inside of silica gel display closer resemblance
      to its solution behavior, more so than liposomes, and that the MSP in the NLPs
      maintain the high degree of alpha-helix secondary structure associated with
      functional protein-lipid interactions after entrapment. We also examined the
      effects of residual methanol on lipid phase behavior and the size of NLPs and
      found that it exerts different influences in solution and in silica gel; unlike
      in free solution, silica entrapment may be inhibiting NLP size increase and/or
      aggregation. These findings set precedence for a bioinorganic hybrid nanomaterial
      that could incorporate functional integral membrane proteins. 

PMID- 25062386
TI  - Coping as a caregiver for an elderly family member.
AB  - With nearly 30% of the adult U.S. population acting as caregivers for sick,
      disabled, or elderly family members, it is imperative that caregivers become
      better equipped to cope with this challenging role. Although caregiving is
      regarded as an arduous endeavor, caring for an older family member may actually
      produce positive experiences. This study examines how caregivers use
      communication as a tool to cope with caring for an older family member. Over a
      span of 15 months, more than 150 caregiver stories were gathered from
      AgingCare.com, analyzed thematically, and categorized. The results show that
      stories utilize emotion-based techniques, including humor (20%), positive framing
      (16%), and acceptance (11%), to reveal that lasting, meaningful bonds can develop
      between caregivers and caregivers' relatives. These techniques allow caregivers
      to redefine their familial role and to find comfort in disheartening situations.
      Thus, coping is a truly communicative event since emotions can facilitate
      behaviors directed at ailing family members. 

PMID- 25062387
TI  - Diversity-oriented syntheses: coupling reactions between electron-deficient
      olefins and aryl aldehydes via C(sp2)-H functionalization.
AB  - A diversity-oriented syntheses by coupling three electron-deficient olefins
      (vinyl sulfonamides, methacrylamides, and methyl acrylates, respectively) with
      aryl aldehydes via C(sp(2))-H functionalization were reported. These reactions
      gave four different skeletal products respectively under environment-friendly and
      mild conditions. All these reactions are highly regioselective and effective,
      very suitable for the preparation of synthetic building blocks and compound
      library, the results will enrich current coupling chemistry of olefins with
      aldehydes and can be applied to other chemistry areas as well. 

PMID- 25062390
TI  - STOP STEMI(c)-a novel medical application to improve the coordination of STEMI
      care: a brief report on door-to-balloon times after initiating the application.
AB  - OBJECTIVE: The objective of our study was to evaluate the effect of the STOP
      STEMI(c) medical application on door-to-balloon (D2B) time in patients arriving
      to our emergency department with an acute ST Elevation Myocardial Infarction
      (STEMI). STOP STEMI(c) is a novel medical application developed by physicians to
      improve the coordination and communication tasks essential to rapid assessment
      and care of the patients suffering from a STEMI. METHODS: We conducted a
      retrospective before and after review of the Good Shepherd Health System STEMI
      quality assurance/improvement dashboard for a 10-month period between November,
      2012 and September, 2013 (4 months before STOP STEMI(c) and 6 months after). Data
      was collected using a standard data collection form and entered on the dashboard
      by a STEMI coordinator blinded to study objectives. We calculated the average D2B
      times before and after initiation of STOP STEMI(c) along with the improvement in
      the benchmarks of D2B less than 90 min and D2B less than 60 minutes. A subgroup
      analysis of Center for Medicare and Medicaid services (CMS) reportable cases was
      conducted to evaluate these benchmarks in the subset of patients meeting the
      criteria for CMS reporting by our facility. RESULTS: During the study period, we
      received 155 STEMI patients, average 0.5 patients per day. One hundred twelve of
      the patients underwent percutaneous coronary intervention (PCI), 37 preSTOP
      STEMI(c), and 75 postSTOP STEMI(c). Of the 112 PCI cases, 7 were excluded leaving
      105 cases for analysis, 36 preapplication and 69 postapplication. We found a 22%
      reduction in the average door-to-balloon time after implementing the STOP
      STEMI(c) application (91-71 minutes) respectively, the average difference of 20
      minutes P = 0.05 (95% CI, -1-40minutes). In the analysis of CMS reportable cases
      (n = 64 cases), we observed a decrease in the average D2B of 15 minutes (68-53
      minutes), a 22% reduction P = 0.03 (95% CI 1-29min). In the CMS reportable cases,
      we saw an improvement in the D2B time less than 90 minutes from 78-95% and less
      than 60 minutes D2B improvement from 56-80%. We also observed an appropriate
      absolute reduction in PCI resource utilization by 11%. CONCLUSIONS: In this
      cohort of patients, the utilization of STOP STEMI(c) decreased the average door
      to-balloon times by 22% in the patients with acute STEMI arriving at our
      emergency department. This effect was maintained when looking at the subset of
      all STEMI cases reportable to CMS. We also observed modest improvements in
      meeting the less than 60-minute, less than 90-minute benchmarks, and improvements
      in the resource utilization.

PMID- 25062389
TI  - Free-living amoebae (FLA) co-occurring with legionellae in industrial waters.
AB  - Legionella pneumophila is known as the causative agent of Legionnaires' disease
      and free-living amoebae (FLA) can serve as vehicles for legionellae. The aim of
      this study was to screen industrial waters for the occurrence of FLA and their co
      occurrence with legionellae. A total of 201 water samples, including 129 cooling
      waters and 72 process waters, and 30 cooling lubricants were included in the
      study. Treated waters were screened periodically, pre and post treatment.
      Altogether, 72.6% of the water samples were positive for FLA, acanthamoebae being
      most prevalent (in 23.9% of the samples) followed by Vermamoeba vermiformis
      (19.4%). Only one cooling lubricant was positive (Acanthamoeba genotype T4).
      Legionella spp. were detected in 34.8% of the water samples and in 15% in high
      concentrations (>1000 CFU/100 ml). Altogether, 81.4% of the Legionella-positive
      samples were positive for FLA by standard methods. By applying a highly sensitive
      nested PCR to a representative set of random samples it was revealed that
      Legionella spp. always co-occurred with Acanthamoeba spp. Although the addition
      of disinfectants did influence amoebal density and diversity, treated waters
      showed no difference concerning FLA in the interphases of disinfection. It
      appears that FLA can re-colonize treated waters within a short period of time.

PMID- 25062388
TI  - An allosteric modulator of HIV-1 protease shows equipotent inhibition of wild
      type and drug-resistant proteases.
AB  - NMR and MD simulations have demonstrated that the flaps of HIV-1 protease (HIV
      1p) adopt a range of conformations that are coupled with its enzymatic activity.
      Previously, a model was created for an allosteric site located between the flap
      and the core of HIV-1p, called the Eye site (Biopolymers 2008, 89, 643-652).
      Here, results from our first study were combined with a ligand-based, lead
      hopping method to identify a novel compound (NIT). NIT inhibits HIV-1p,
      independent of the presence of an active-site inhibitor such as pepstatin A.
      Assays showed that NIT acts on an allosteric site other than the dimerization
      interface. MD simulations of the ligand-protein complex show that NIT stably
      binds in the Eye site and restricts the flaps. That bound state of NIT is
      consistent with a crystal structure of similar fragments bound in the Eye site
      (Chem. Biol. Drug Des. 2010, 75, 257-268). Most importantly, NIT is equally
      potent against wild-type and a multidrug-resistant mutant of HIV-1p, which
      highlights the promise of allosteric inhibitors circumventing existing clinical
      resistance.

PMID- 25062391
TI  - Noise versus signal: the clinical implications of an increasingly sensitive
      troponin assay for patients with suspected acute coronary syndrome.
AB  - OBJECTIVES: To evaluate the clinical impact of a troponin assay switch in
      suspected acute coronary syndromes (ACS). METHODS: Retrospective analysis of ACS
      cases in the 3 months before and after changing to a contemporary, higher
      sensitivity troponin assay. Admitting diagnosis, proportion with a positive
      result, initial treatment and testing, coronary artery intervention, inhospital
      events, and final discharge diagnosis were compared by assay group. RESULTS:
      Seven hundred seventy patients were included: 319 (41.4%) preassay and 451
      (58.6%) postassay. Preassay change, non-ST segment elevation myocardial
      infarction at admission (43.0% vs. 70.5%; diff [95% confidence interval (CI)] = 
      27.5 [-34.2, -20.6]) was diagnosed less often, and a positive troponin was less
      common (33.2% vs. 72.3%; diff [95% CI] = -39.1 [-45.4, -32.2]). However,
      anticoagulation (53.3% vs. 42.4%; diff [95% CI] = 10.9 [3.8, 18.0]) and cardiac
      catheterization use were more frequent (53.9% vs. 41.9%; diff [95% CI] = 12.0
      [19.0, 48.5]). There was no difference in coronary intervention (41.9% vs. 40.7%;
      diff [95% CI] = 1.2 [-9.0, 11.2]) by assay period. Inhospital event were rare
      (unstable ventricular arrhythmia = 1.2%, cardiac arrest = 3.4%, death = 4.4%)
      with no difference between groups. A non-ACS diagnosis at discharge was more
      common in the postassay group (31.6% vs. 46.5%; diff [95% CI] = 14.9 [7.9,
      21.6]). CONCLUSIONS: Although non-ST segment elevation myocardial infarction
      diagnosis at admission and a positive troponin were more frequent postassay
      change, rates of anticoagulation and cardiac catheterization were lower and a non
      ACS diagnosis at discharge was more common. These data suggest an evolving
      understanding and clinical impact of contemporary troponin assays when used in
      real-world settings.

PMID- 25062392
TI  - Ranolazine refractory angina registry: 1-year results.
AB  - Patients with refractory angina (RA) have limited therapeutic options and
      significant limitations in their quality of life. Ranolazine is approved for
      patients with chronic stable angina but has not been studied in patients with RA.
      The Ranolazine Refractory Angina Registry was designed to evaluate the safety,
      tolerability, and effectiveness in RA patients. In a dedicated RA clinic using an
      extensive prospective database, 100 patients were enrolled. Angina class,
      medications, major adverse cardiac events including death, myocardial infarction,
      and revascularization were obtained at 1, 6, and 12 months. Overall 43% of
      patients had a >=2 class improvement in angina. At 1 year, 57% patients remained
      on ranolazine (91.2%; 500 mg BID), including 58% with a >=2 class improvement in
      angina. Reasons for discontinuation included: side effects (n = 16), major
      adverse cardiac events (n = 10), cost (n = 5), ineffective (n = 6), cost and
      ineffective (n = 3), and unknown (n = 3). In conclusion, ranolazine is an
      effective antianginal therapy in patients with RA; still at 1 year only 57% of
      patients remained on ranolazine because of side effects, suboptimal
      effectiveness, cost, or progression of disease. 

PMID- 25062393
TI  - Emergency physicians' acute coronary syndrome testing threshold and diagnostic
      performance: acute coronary syndrome critical pathway with return visit feedback.
AB  - OBJECTIVES: Emergency physician threshold to test for acute coronary syndrome
      (ACS) is directly related to ACS diagnosis rate and inversely related to ACS
      missed diagnosis rate. Feedback to emergency physicians of information on their
      prior patients whose ACS diagnosis was not identified may improve physician
      diagnostic performance. METHODS: A critical pathway for evaluation of patients
      for ACS was modified to include feedback to physicians on their cases who had a
      return visit and did not have their ACS diagnosis identified at their prior
      emergency department visit. Feedback included case-specific details, discussion
      of the case at the monthly Morbidity and Mortality conference, and a yearly a
      report to each physician comparing their performance to their peers (ACS
      evaluation rate, ACS diagnosis rate, and ACS missed diagnosis rate). Cases were
      identified, and physician-specific performance was calculated from a computerized
      encounter database at 2 community teaching hospitals. RESULTS: During the study
      period, 29 emergency physicians evaluated 295,758 patients and identified 6472
      ACS cases. During the study, the yearly ACS evaluation rate for individual
      physician ranged from 19% to 70% (average 40.3%; 95% confidence interval [CI],
      39.5%-41.1%), the yearly ACS diagnosis rate for individual physician ranged from
      1.1% to 4.2% (average 1.7%; 95% CI, 1.65%-1.75%), and the yearly missed ACS
      diagnosis rate for individual physician ranged from 0% to 17% (average 2.8%; 95%
      CI, 2.3%-3.3%). Individual physician ACS evaluation rate was directly related to
      physician ACS diagnosis rate (r 0.76, P = 0.00012) and was inversely related to
      that physician missed ACS rate (r 0.45, P = 0.001). During the study,
      implementation of the critical pathway increased the ACS evaluation rate from 30%
      to 48% and decreased the ACS missed diagnosis rate from 1.5% to 0.3%.
      CONCLUSIONS: Emergency physicians with lower threshold for ACS evaluation more
      frequently diagnose patients with ACS and less frequently miss the diagnosis of
      ACS. Feedback to emergency physicians of information on their patient's return
      visits and their own diagnostic performance may improve outcome for patients with
      ACS.

PMID- 25062394
TI  - False-positive rates of provocative cardiac testing in chest pain patients
      admitted to an emergency department observation unit.
AB  - Emergency department observation units (EDOUs) typically perform routine cardiac
      stress testing or coronary computed tomography (CCTA) to rule out ischemic
      cardiac chest pain. Some have questioned the utility of routine stress testing
      and advanced anatomic imaging in the low-risk chest pain patients. EDOU chest
      pain patients undergoing stress testing or CCTA prior to cardiac catheterization
      between June 1, 2009 and May 31, 2012 were studied in a prospective,
      observational manner. Baseline data, EDOU-related outcomes, and testing results
      were recorded. Stress tests were treadmill echocardiogram or myocardial perfusion
      stress tests and were considered positive if a "positive" or "equivocal"
      interpretation by the reviewing cardiologist prompted cardiac catheterization.
      CCTA was considered positive if it led to subsequent cardiac catheterization.
      Cardiac catheterization was considered positive if subsequent stent placement,
      coronary artery bypass graft (CABG), or change in medical management occurred. Of
      1276 patients evaluated, 112 (8.8%) underwent cardiac catheterization of which 56
      underwent some modality of prior testing. Forty-two of 56 were subject to stress
      testing (30 stress echo and 12 myocardial perfusion) and 14 underwent CCTA prior
      to catheterization. False-positive rate overall was 62.5% (35/56, 95% CI, 48.5%
      74.7%). False-positive rate for stress testing was 75% and 66.7% for perfusion
      and stress echo respectively. False-positive rate for CCTA was 42.9%. It must be
      acknowledged that while these findings do not directly impugn the utility of
      stress testing or CCTA, it may indicate the need for more appropriate patient
      selection to avoid unnecessary cardiac catheterization among EDOU chest pain
      patient cohorts. 

PMID- 25062395
TI  - A standardized bleeding risk score aligns anticoagulation choices with current
      evidence.
AB  - OBJECTIVES: Atrial fibrillation (AF), the most common arrhythmia in elderly
      patients, accounts for 15% of strokes. Oral anticoagulation (OAC) can reduce the
      risk of stroke by 60% but is underprescribed. The HAS-BLED score (Hypertension,
      Abnormal renal or liver function, Stroke, Bleeding, Labile INR, Elderly, Drugs)
      can predict OAC bleeding complications. The authors hypothesized that use of HAS
      BLED can help align decision making with current evidence. METHODS: The authors
      developed a survey with four clinical vignettes designed to highlight the
      complexity in deciding whether to anticoagulate elderly patients with AF.
      Physicians were randomly assigned to receive the survey either including the HAS
      BLED score and the estimated annual risk of bleeding (intervention) or without
      (control). Following each vignette, participants were asked: (1) whether they
      would recommend OAC and (2) to estimate the risk of bleeding and stroke. The
      "appropriate" anticoagulation decision was defined as the choice that minimized
      the risk of stroke and major bleeding. RESULTS: A total of 203 physicians were
      recruited for the survey, with 55 responses obtained (27%). Physicians who were
      given the HAS-BLED score were 18% more likely to choose appropriate
      anticoagulation (74% vs. 56%, P < .05). The HAS-BLED score assisted physicians in
      both choosing to anticoagulate when appropriate and not to anticoagulate when the
      risk of bleeding outweighed the benefit. Overall, physicians were poor at
      estimating the risk of stroke (42% correct) and major bleeding (31% correct).
      CONCLUSIONS: Presentation of the HAS-BLED score led to an 18% improvement in
      appropriate OAC choices. Future study should evaluate incorporation of HAS-BLED
      use in real-time clinical situations.

PMID- 25062396
TI  - Utility of Framingham risk score in urban emergency department patients with
      asymptomatic hypertension.
AB  - Hypertension (HTN) is the primary population-attributable risk for the
      development of heart failure (HF); a disease with devastating consequences
      particularly in urban centers where morbidity and mortality are more pronounced.
      The Framingham Risk Profile (FRP) is widely used to quantify risk for
      cardiovascular disease (CVD), but its applicability in an urban population who
      utilize the emergency department (ED) for primary care is unknown. The objective
      of this study is to evaluate FRP scores in ED patients with asymptomatic HTN and
      subclinical hypertensive heart disease (SHHD). This is a substudy of a
      prospective randomized clinical trial designed to evaluate optimal blood pressure
      (BP) targets. Eligible patients were screened with echocardiography for the
      presence of SHHD and FRP scores were calculated. One hundred forty-nine patients
      enrolled in the study, 133 (89.2%) of whom had detectable SHHD. Mean [SD]
      calculated FRP scores were statistically similar for patients with SHHD versus
      those without (general CVD: 20.2 [8.5] vs. 15.6 [8.7]; P = 0.13 and HF
      calibrated: 2.4 [1.0] vs. 1.8 [1.0]; P = 0.12) corresponding to a calculated risk
      of 15%-30% for subsequent development of CVD. The HF-specific risk score for
      patients with SHHD was 2.4, which equates to a 2.5% risk of HF development in 10
      years. The FRP correctly identified those with SHHD as high-risk for general CVD
      but appeared to underestimate the likelihood of HF. Recalibration of the HF
      adjustment factor and inclusion of additional data elements such as
      echocardiography is needed to enhance applicability of the FRP in this setting. 

PMID- 25062397
TI  - 2014 Oman Heart Association protocol for the management of acute atrial
      fibrillation.
AB  - Although atrial fibrillation (AF) is the most common cardiac arrhythmia, there is
      variation in practice with regard to the management of acute AF among the
      hospitals and even within the same hospital in Oman. This variation likely
      reflects a lack of high-quality evidence. Standard guidelines and textbooks do
      not offer clear evidence-based direction for physicians to guide the management
      of acute AF. Particularly controversial is the issue of using rhythm control or
      rate control. This stimulated Oman Heart Association (OHA) to issue a simplified
      protocol for the management of acute AF to be applied by the entire cardiac
      caregivers all over the country. The priorities for acute management of AF
      include stabilizing the patient's hemodynamic status, symptom control, treatment
      of the underlying and precipitating cause, and more importantly protecting the
      brain. 

PMID- 25062398
TI  - Esophageal gastrointestinal stromal tumor: is tumoral enucleation a viable
      therapeutic option?
AB  - OBJECTIVE: The primary objective was to evaluate the feasibility of surgical
      enucleation of esophageal gastrointestinal stromal tumors (E-GISTs). Secondary
      objectives evaluated (i) the impact of tumor enucleation on oncological outcomes,
      (ii) the effect of pretherapeutic biopsy on the feasibility of E-GIST
      enucleation, and (iii) the impact of mucosal ulceration on outcome. BACKGROUND: E
      GISTs are very rare tumors and esophageal resection has been the recommended
      approach. The feasibility and impact on outcomes of tumor enucleation are
      unknown. METHODS: Through a large national multicenter retrospective study, 19
      patients with E-GISTs were identified between 2001 and 2010. Patients who
      underwent either enucleation or esophagectomy were compared. RESULTS: Of over 19
      patients identified with E-GISTs, curative treatment was surgical for 16
      patients, with enucleation in 8 and esophagectomy in 8. In the enucleation group,
      median tumoral diameter was 40 mm (18-65 mm), without any mucosal ulceration,
      preoperative capsular ruptures, or incomplete resections. In the esophagectomy
      group, the median tumoral diameter was 85 mm (55-250 mm), with mucosal ulceration
      in 4 patients, preoperative capsular rupture in 1, and no incomplete resections.
      Severe postoperative complication rates were 50% and 25% in the esophagectomy and
      enucleation groups, respectively, with 2 postoperative deaths after
      esophagectomy. After a median follow-up of 6.4 years, 2 recurrences were observed
      after esophagectomy versus 0 after enucleation. Endoscopic biopsies did not
      expose patients to complications or local recurrence after enucleation.
      Endoscopic mucosal ulceration was associated with more aggressive tumors.
      CONCLUSIONS: E-GIST enucleation seems safe for tumors of less than 65 mm in
      diameter.

PMID- 25062399
TI  - A learning agenda for abortion stigma: recommendations from the Bellagio expert
      group meeting.
AB  - Stigma discredits individuals, communities, and institutions and marks them as
      inferior. The stigma surrounding abortion plays a critical role in its social,
      medical, and legal marginalization around the world. Based on the existing field
      of knowledge, in June 19, 2012, researchers, practitioners, and advocates from 11
      countries participated in an intensive meeting on abortion stigma to refine a
      conceptual framework for abortion stigma and set a future learning agenda to
      guide research and programmatic efforts to address abortion stigma.

PMID- 25062400
TI  - Recent advances in transition-metal-catalyzed functionalization of unstrained
      carbon-carbon bonds.

PMID- 25062401
TI  - Self-attempted labioplasty with elastic bands resulting in severe necrosis.
AB  - BACKGROUND: Labial hypertrophy is protuberant labial tissue extending beyond the
      labia majora. Self-perception of poor cosmetic appearance is common in young
      patients and not necessarily pathologic. Labioplasty is indicated for patients
      with persistent symptoms including entrapment and painful intercourse. CASE: A 26
      year-old woman presented with genital pain and foul odor after self-applying
      elastic bands to her labia minora. The bands were applied for a self-perceived
      abnormal appearance and lack of insurance for medical consultation. Surgical
      debridement and revision of the labia were performed using a straight vertical
      approach. CONCLUSIONS: Self-attempted labioplasty can result in necrosis and
      infection. Education and counseling of patients on the normal variants of labial
      anatomy and the recommended therapeutic methods will lead to better cosmetic
      results and prevent self-mutilation.

PMID- 25062402
TI  - Glassy cell carcinoma of the cervix and metastasis in episiotomy scar: a case
      report.
AB  - OBJECTIVE: The authors describe the 20th known case of cervical cancer with
      metastasis in an episiotomy scar, being the first case describing an implant of
      malignant cells in the episiotomy scar associated with glassy cell carcinoma.
      MATERIALS AND METHODS: One case report. RESULTS: We describe the case of a 34
      year-old woman, with cervical cancer diagnosed 1 month after delivery. Four
      months later, a radical hysterectomy was performed. During surgery, a nodule at
      the site of the episiotomy scar was identified and removed. The histologic
      diagnosis revealed a glassy cell carcinoma of the cervix, with metastasis in the
      episiotomy scar. After surgery, chemotherapy and radiotherapy were performed. The
      disease progressed rapidly, and the patient died 9 months after surgery.
      CONCLUSIONS: The implantation of neoplastic cells in the perineum is a potential
      risk of vaginal delivery, with a 40% mortality rate. It thus seems advisable to
      avoid vaginal delivery as much as possible when cervical cancer is diagnosed
      during pregnancy. Given the rarity, there are no studies on the most effective
      treatment in such situations.

PMID- 25062403
TI  - Spindle cell sarcoma of the vulva with myofibroblastic differentiation.
AB  - OBJECTIVE: Primary vulvar sarcomas are rare lesions of the lower genital tract.
      We report the case of a patient with a spindle cell sarcoma of the vulva.
      MATERIALS AND METHODS: A 44-year-old woman presented with a painless vulvar mass.
      Vulvar biopsy demonstrated a spindle cell sarcoma with myofibroblastic
      differentiation. RESULTS: Pretreatment evaluation revealed no evidence of
      metastatic disease, and magnetic resonance imaging found no local masses. The
      patient underwent right radical vulvectomy with negative margins and tolerated
      the procedure well. CONCLUSIONS: Women undergoing gynecologic care should have
      routine evaluation of the vulva to detect these rare neoplasms.

PMID- 25062404
TI  - Omega-3 fatty acids and cardiovascular disease: epidemiology and effects on
      cardiometabolic risk factors.
AB  - Clinical and epidemiological studies provide support that the polyunsaturated
      omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid from fish and
      fish oils are cardioprotective, particularly in the setting of secondary
      prevention. Omega-3 fatty acids benefit multiple cardiometabolic risk factors
      including lipids, blood pressure, vascular reactivity and cardiac function, as
      well as having antithrombotic, anti-inflammatory and anti-oxidative actions.
      Omega-3 fatty acids do not associate with any adverse effects and do not
      adversely interact with prescriptive drugs such as lipid-lowering,
      antihypertensive or hypoglycaemic medications. Clinical studies suggest that
      doses up to 4 g daily when prescribed with anticoagulant or antiplatelet drugs do
      not associate with increased risk of major bleeding episodes. Omega-3 fatty acids
      have gained widespread usage by general practitioners and clinicians in clinical
      settings such as pregnancy and infant development, secondary prevention in
      coronary heart disease patients and treatment of dyslipidaemias. Health
      authorities currently recommend an intake of at least two oily fish meals per
      week for the general population which equates to approximately 500 mg per day of
      eicosapentaenoic acid and docosahexaenoic acid. In patients with coronary heart
      disease the guidelines recommend 1 g daily supplements and in
      hypertriglyceridaemic patients up to 4 g per day. These doses are now achievable
      with readily available purified encapsulated preparations of omega-3 fatty acids.
      However, a more practical recommendation for increasing omega-3 fatty acid intake
      in the general population is to incorporate fish as part of a healthy diet that
      includes increased consumption of fruits and vegetables, and moderation of salt
      intake. 

PMID- 25062405
TI  - Cell size as a key determinant of phytoplankton metabolism and community
      structure.
AB  - Phytoplankton size structure controls the trophic organization of planktonic
      communities and their ability to export biogenic materials toward the ocean's
      interior. Our understanding of the mechanisms that drive the variability in
      phytoplankton size structure has been shaped by the assumption that the pace of
      metabolism decreases allometrically with increasing cell size. However, recent
      field and laboratory evidence indicates that biomass-specific production and
      growth rates are similar in both small and large cells but peak at intermediate
      cell sizes. The maximum nutrient uptake rate scales isometrically with cell
      volume and superisometrically with the minimum nutrient quota. The unimodal size
      scaling of phytoplankton growth arises from ataxonomic, size-dependent trade-off
      processes related to nutrient requirement, acquisition, and use. The superior
      ability of intermediate-size cells to exploit high nutrient concentrations
      explains their biomass dominance during blooms. Biogeographic patterns in
      phytoplankton size structure and growth rate are independent of temperature and
      driven mainly by changes in resource supply. 

PMID- 25062406
TI  - Reflections on my career as a marine physical chemist, and tales of the deep.
AB  - This is a personal review of how one can apply the principles of physical
      chemistry to study the ocean and other natural waters. Physical chemistry is the
      study of chemical thermodynamics, kinetics, and molecular structure. My long-term
      interest in the chemistry of seawater is an extension of my early work on water
      and the interactions that occur in aqueous electrolyte solutions, which I began
      as part of my PhD research on the thermodynamics of organic acids in water. Over
      the years, I have attempted to apply the tools of physical chemistry to elucidate
      the structures of seawater, brines, lakes, and rivers. I have developed and
      continue to work on ionic interaction models that can be applied to all natural
      waters. Here, I reflect on how my students, postdocs, research assistants, and
      scientific colleagues have influenced my life, my career, and the field of marine
      physical chemistry. My hope was and is to use these tools to understand the
      molecular structures of natural waters. 

PMID- 25062407
TI  - Molecular cloning and functional characterization of a novel CBL-interacting
      protein kinase NtCIPK2 in the halophyte Nitraria tangutorum.
AB  - CBL-interacting protein kinases (CIPKs) mediate many plant responses to abiotic
      stress. However, their functions are poorly understood in halophytes. In this
      study, we isolated a CIPK gene, NtCIPK2, from the halophyte Nitraria tangutorum.
      By sequence alignment and the construction of a phylogenetic tree, we found that
      NtCIPK2 is similar to CIPK2 proteins from other plants, and contains conserved
      domains and motifs. The promoter of NtCIPK2 harbors many cis-acting elements that
      might be recognized and bound by transcription factors that are related to
      hormones and stress responses. NtCIPK2 was ubiquitously and robustly expressed in
      all tested organs, and was induced by salinity, drought, heat, and cold stress.
      The overexpression of NtCIPK2 in Escherichia coli caused better growth against
      high salinity, alkalinity, and osmotic conditions, dehydration, and extreme
      temperatures (i.e., heat and cold) compared to the control. Thus, NtCIPK2 is a
      candidate gene that might improve the stress tolerance of crops and herbs through
      genetic manipulation. 

PMID- 25062408
TI  - Effects of different doses of Savda Munziq on myocardial ischemia-reperfusion
      injury in rats with abnormal Savda syndrome.
AB  - To investigate the effects of different doses of abnormal Savda Munziq on
      myocardial ischemia-reperfusion injury (MI/RI) in rats with the abnormal Savda
      syndrome, 50 abnormal Savda animal models were randomly divided into a control
      group, a model group, a high-dose group, a middle-dose group, and a low-dose
      group, with each group containing 10 rats. The enzyme-linked immunosorbent assay
      was used to detect the serum myocardial enzyme and troponin levels, and
      hematoxylin and eosin (HE) staining was used to observe changes of the myocardial
      tissues in the different groups. Results showed that in the Munziq intervention
      groups, the serum creatine kinase and troponin levels were significantly lower
      than those in the model group, and the middle-dose group showed the lowest
      levels. The HE staining of myocardial tissue showed that the myocardial edema and
      muscle fiber proliferation levels were significantly higher in the Munziq
      intervention groups than in the model group, and the middle-dose group showed the
      least cardiac tissue damage. Therefore, intervention with an intermediate Munziq
      dose could significantly reduce MI/RI in rats with abnormal Savda syndrome. 

PMID- 25062409
TI  - Relationship between progeny growth performance and molecular marker-based
      genetic distances in Eucommia ulmoides parental genotypes.
AB  - Progeny performances, variations and combining abilities for growth traits were
      evaluated in a factorial mating design of Eucommia ulmoides. Three marker
      systems, sequence-related amplified polymorphism, amplified fragment length
      polymorphism, and inter-simple sequence repeat, were used to determine genetic
      distances between parents. Correlations of genetic distances with progeny
      performances, within-family coefficients of variation and specific-combining
      abilities were established for height and basal diameter traits. Significant
      positive correlations were found between progeny performances of growth traits
      and genetic distances of parents based on sequence-related amplified polymorphism
      markers or a combination of all 3 marker systems. This revealed that crosses
      between genetically distant parents produced progenies with excellent growth
      performances. The lack of correlations between parental genetic distances and
      within-family coefficients of variation or specific-combining abilities suggested
      that these characteristics were unpredictable. The results of this study
      represent a potential criterion to predict progeny performances and choose
      parents in the breeding program. 

PMID- 25062410
TI  - Lactoferrin mRNA expression in mouse mammary glands during pregnancy and
      lactation.
AB  - Lactoferrin (Lf) is an iron-binding glycoprotein that is produced by mucosal
      epithelial cells in mammals. Lf has non-immune natural defense functions and
      biological functions in addition to and distinct from its role in regulating
      inflammatory responses. Lf also improved some physiological and immunological
      parameters. Lf is a biomarker for monitoring medical treatment in inflammatory
      bowel diseases. Current LF research focuses on iron absorption, antimicrobial
      activity, and the modulation of iron metabolism during inflammation. No
      systematic research about Lf expression levels in mouse mammary glands during
      pregnancy and lactation exists. We investigated Lf mRNA expression levels in
      mouse mammary glands by collecting samples on days 1, 6, 12, and 18 of pregnancy
      and lactation (six mice per group). The expression levels of Lf mRNA were
      measured by semi-quantitative reverse transcription polymerase chain reaction
      using GAPDH as an internal control. Lf mRNA was not expressed in mammary glands
      on days 1, 6, and 12 of pregnancy, but it was expressed on day 18 (IOD:
      integrated optical density; Lf(IOD)/GAPDH(IOD) = 0.46). Lf expression levels were
      higher during lactation stages than during pregnancy stages, and it stabilized at
      0.71-0.73 (Lf(IOD)/GAPDH(IOD)) from day 1 to 12 of lactation; however, the
      difference was not significant (P > 0.05). At day 18 of lactation, Lf expression
      began to decline (Lf(IOD)/GAPDH(IOD) = 0.61), but the difference was not
      significant (P > 0.05). Based on these results, the variation in Lf expression
      levels during developmental stages may be related to its regulatory role in mouse
      mammary gland immunity.

PMID- 25062411
TI  - Genetic diversity of HLA-DRB1 alleles in the Tujia population of Wufeng, Hubei
      Province, China.
AB  - We established a genetic database by investigating human leukocyte antigen (HLA)
      DRB1 allelic frequencies in a disease-association study in the Tujia population
      in Wufang, Hubei, China. The allele frequencies of the HLA-DRB1 locus in 262
      healthy, unrelated Tujia individuals living in the Wufeng region of the Hubei
      Province were analyzed using the Luminex HLA sequence-specific oligonucleotide
      method with a WAKFlow HLA typing kit. A total of 13 alleles were detected at the
      HLA-DRB1 locus. HLA-DRB1*09 was the most common allele (22.52%), followed by
      DRB1*08 and DRB1*15 (11.07%), and DRB1*12 and DRB1*04 (10.69%). These data were
      compared with the results obtained for 10 other ethnic groups living in other
      regions as well as to Han groups using neighbor-joining dendrograms and principal
      component analysis. The results showed that the Tujia population has a close
      genetic relationship with the Middle Han population at the HLA-DRB1 locus. This
      information will be useful for HLA-DRB1-linked disease-association studies. 

PMID- 25062412
TI  - Molecular characterization of Anthurium genotypes by using DNA fingerprinting and
      SPAR markers.
AB  - We characterized single primer amplification reaction (SPAR) molecular markers
      from 20 genotypes of Anthurium andraeanum Lind., including 3 from commercial
      varieties and 17 from 2 communities in the State of Espirito Santo, Brazil.
      Twenty-four SPAR, consisting of 7 random amplified polymorphic DNA and 17 inter
      simple sequence repeat markers were used to estimate the genetic diversity of 20
      Anthurium accessions. The set of SPAR markers generated 288 bands and showed an
      average polymorphism percentage of 93.39%, ranging from 71.43 to 100%. The
      polymorphism information content (PIC) of the random amplified polymorphic DNA
      primers averaged 0.364 and ranged from 0.258 to 0.490. Primer OPF 06 showed the
      lowest PIC, while OPAM 14 was the highest. The average PIC of the inter-simple
      sequence repeat primers was 0.299, with values ranging from 0.196 to 0.401.
      Primer UBC 845 had the lowest PIC (0.196), while primer UCB 810 had the highest
      (0.401). By using the complement of Jaccard's similarity index and unweighted
      pair group method with arithmetic mean clustering, 5 clusters were formed with a
      cophenetic correlation coefficient of 0.8093, indicating an acceptable clustering
      consistency. However, no genotype clustering patterns agreed with the
      morphological data. The Anthurium genotypes investigated in this study are a
      germplasm source for conservational research and may be used in improvement
      programs for this species.

PMID- 25062413
TI  - New roles of filopodia and podosomes in the differentiation and fusion process of
      osteoclasts.
AB  - The cytoskeleton mediates various cellular processes such as differentiation and
      fusion, including in the filopodia and podosomes. However, apart from cell
      migration and formation of the sealing zone, little is known regarding the
      changes and related regulatory mechanisms of the cytoskeleton and additional
      roles of the filopodia and podosomes during the differentiation and fusion of
      osteoclasts. The cytomorphology and cytoskeleton of osteoclasts in the
      differentiation process were evaluated using tartrate-resistant acid phosphatase
      staining and immunofluorescence staining. Moreover, the expression levels of Rho
      GTPases and enzymes related to osteoclast differentiation and bone resorption
      were detected by quantitative reverse transcription-polymerase chain reaction. We
      detected 3 types of filopodia in osteoclast precursors and only 1 type of
      filopodia in undifferentiated cells. Mature osteoclasts were completely devoid of
      filopodia. Interestingly, cell fusion was highly specific, and the fusion
      initially occurred to the filopodia. Confocal images revealed that F-actin and
      microtubules significantly differed among fused cells. These results suggest that
      filopodia and podosomes not only play important roles in cell migration and the
      formation of sealing zones but also in the pre-fusion selectivity of 2 cells and
      the movement direction of the cell nucleus and cytoplasm during the fusion
      process. In addition, cdc42v1, RhoU, and RhoF regulate the formation of 3 types
      of filopodia during various stages of differentiation, while Rac1, Rac2, and
      filament A may be associated with cell selectivity during the fusion process. 

PMID- 25062414
TI  - HLA-B51 subtypes in Turkish patients with Behcet's disease and their correlation
      with clinical manifestations.
AB  - Behcet's disease (BD) is a multisystemic inflammatory disease believed to be
      triggered by microbial or environmental factors on a genetic platform.
      Clinically, it may have an impact on many body systems, including the
      mucocutaneous, ocular, articular, vascular, and neurological systems. In this
      study, we aimed to determine the HLA-B51 subtypes and their correlations with the
      clinical findings of BD. Fifty-one patients with BD and 44 gender- and age
      matched healthy subjects were included in this study. The HLA-B51 subtypes of all
      participants were determined, and the correlations of the clinical manifestations
      of the disease with the HLA-B51 subtypes were analyzed. HLA-B51 positivity was
      found to be significantly higher in the patient group (P < 0.001, RR = 15.20),
      which had significantly more frequent HLA-B5101, HLA-B5102(01), HLA-B5109, and
      HLA-B5122 subtypes than the healthy subjects (all P < 0.05). Furthermore,
      considering the correlation between the genetic makeup and clinical findings, the
      HLA-B5109 subtype was found to be less frequent in patients with papulopustular
      skin lesions (P = 0.042). The frequency of HLA-B5103 was significantly higher in
      patients with central nervous system involvement (P = 0.015). There may be a
      relationship between HLA-B5102(01), HLA-B5109, and HLA-B5122 in addition to HLA
      B51 and HLA-B5101(01) in Turkish patients with BD. The HLA-B5109 subtype can be
      protective against papulopustular lesion development; however, the HLA-B5103
      subtype may pose a risk for neuro-Behcet development in BD.

PMID- 25062415
TI  - Efficiency of circulant diallels via mixed models in the selection of papaya
      genotypes resistant to foliar fungal diseases.
AB  - Diallel crossing methods provide information regarding the performance of
      genitors between themselves and their hybrid combinations. However, with a large
      number of parents, the number of hybrid combinations that can be obtained and
      evaluated become limited. One option regarding the number of parents involved is
      the adoption of circulant diallels. However, information is lacking regarding
      diallel analysis using mixed models. This study aimed to evaluate the efficacy of
      the method of linear mixed models to estimate, for variable resistance to foliar
      fungal diseases, components of general and specific combining ability in a
      circulant table with different s values. Subsequently, 50 diallels were simulated
      for each s value, and the correlations and estimates of the combining abilities
      of the different diallel combinations were analyzed. The circulant diallel method
      using mixed modeling was effective in the classification of genitors regarding
      their combining abilities relative to the complete diallels. The numbers of
      crosses in which each genitor(s) will compose the circulant diallel and the
      estimated heritability affect the combining ability estimates. With three crosses
      per parent, it is possible to obtain good concordance (correlation above 0.8)
      between the combining ability estimates. 

PMID- 25062416
TI  - Atorvastatin in combination with ezetimibe and carotid atherosclerosis.

PMID- 25062417
TI  - Antigenotoxic and antimutagenic effects of glutamine supplementation on mice
      treated with cisplatin.
AB  - We evaluated the effects of glutamine on clastogenic and genotoxic damage
      prevention caused by the administration of cisplatin. Forty Swiss mice were
      divided into 8 experimental groups: G1 and G2, which were control groups; G3, G4,
      and G5, which were administered [2 doses of glutamine (orally)] separated by a 24
      h period (150, 300, and 600 mg/kg, respectively), and a dose of phosphate
      buffered saline by intraperitoneal injection; G6, G7, and G8, which were treated
      in the same manner as the previous groups, but received cisplatin rather than
      phosphate-buffered saline. The antimutagenicity groups showed damage reduction
      percentages of 79.05, 80.00, and 94.27% at the time point T1, 53.18, 67.05, and
      64.74 at time point T2 for the 150, 300, and 600 mg/kg doses of glutamine,
      respectively. Antigenotoxic activity was evident for all 3 doses with damage
      reduction percentages of 115.05, 119.06, and 114.38 for the doses of glutamine of
      150, 300, and 600 mg/ kg, respectively. These results suggest that further
      studies are needed to confirm the clastogenic activity of glutamine. However, our
      results may lead to rational strategies for supplementation of this antioxidant
      as an adjuvant in cancer treatment or for preventing genomic lesions. 

PMID- 25062418
TI  - FAS -670A>G promoter polymorphism is associated with soluble Fas levels in
      primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a chronic systemic autoimmune disease
      characterized by lymphocytic infiltration of exocrine glands. Soluble Fas
      receptor (sFas) has been suggested as a Fas-mediated apoptosis blocker that could
      impair clonal deletion in infiltrated autoreactive cells. The FAS -670A>G
      promoter polymorphism has been studied in pSS. However, a relationship between
      FAS -670A>G promoter polymorphism and sFas levels in pSS had not been found. We
      examined this relationship in 77 Mexican pSS patients and 84 healthy subjects
      were included. Genotypes were identified by PCR-RFLP, and Fas soluble levels were
      quantified by ELISA. No significant differences between allele and genotype
      frequencies were found between these two groups. The sFas levels in the serum of
      pSS patients were significantly higher than in controls (9961 vs 8840 pg/mL,
      respectively). In addition, AA genotype carriers had significantly higher levels
      of sFas than GG carriers (pSS: 10,763 and 9422 pg/mL; controls: 9712 and 8305
      pg/mL, respectively). An additive model analysis between genotypes (AG+GG vs AA)
      in both groups, demonstrated a significant association between carriers of the A
      allele and high sFas levels. In conclusion, carrying the double dose of A allele
      of FAS -670A>G polymorphism is associated with high levels of sFas in pSS, but it
      is not a susceptibility marker for pSS. 

PMID- 25062419
TI  - Antibody preparation and identification of the Cashmere goat c-kit protein in the
      testes.
AB  - The c-kit protein plays a major role in the regulation of germ cell development.
      Its expression and distribution in rodent testes have been widely reported.
      However, research regarding c-kit expression in domestic animals is scarce, and
      the expression pattern and distribution of c-kit in germ cells have not been
      clearly defined. In this study, a specific antigenic region for goat c-kit was
      designed, and a c-kit polyclonal antibody was prepared. This antibody was then
      applied in a study evaluating c-kit expression in Cashmere goat tissues. A
      Western blot analysis showed that three forms of c-kit were expressed in goat
      testes: precursor, mature, and soluble c-kit. Fluorescent immunohistochemical
      analyses showed that c-kit was primarily expressed in the spermatogonia and
      spermatocytes of goat testes. These results not only clarify the expression and
      localization of c-kit in the goat testis, but also accelerate further research
      regarding the function of c-kit in goat spermatogenesis. 

PMID- 25062420
TI  - Intervention for prehypertension and its cardiovascular risk factors in Inner
      Mongolia.
AB  - Blood pressure levels were evaluated among prehypertension patients with
      associated cardiovascular risk factors to determine the effect of different
      interventions with respect to new endpoint events. A total of 1112 patients were
      equally and randomly divided into control, lifestyle, drug, and lifestyle + drug
      groups, and were followed-up for 12 months. We collected the age, height, weight,
      blood pressure, heart rate, blood lipid levels, blood glucose levels, and other
      clinical data from all subjects at the baseline and at the end of the follow-up
      period. The average systolic blood pressure (SBP) and diastolic blood pressure
      (DBP) in the intervention groups were significantly reduced after the
      intervention (lifestyle + drug > drug > lifestyle). SBP and DBP were higher in
      the control group than before intervention (P < 0.05). Age, gender, heart rate,
      triglyceride (TG) levels, body mass index (BMI), alcohol consumption, and family
      history were the major factors affecting blood pressure. Increased BMI, TG, high
      sensitivity C-reactive protein, alcohol consumption, family history, SBP, and DBP
      were major risk factors of hypertension. At the end of the follow-up period,
      there were 67 cases of hypertension, 32 cases of diabetes, and 12 cases of the
      endpoint events. Hypertension and diabetes events were reduced in the
      intervention groups relative to the control group (P < 0.05). The number of cases
      with incident cardiovascular endpoints did not differ among the three
      intervention groups (P > 0.05). Therefore, hypertension and related
      cardiovascular events can be controlled with different interventions. 

PMID- 25062421
TI  - Isolation, identification, and antioxidant activity of polysaccharides from the
      shell of abalone (Haliotis discus hannai Ino).
AB  - In this study, two antioxidative substances, a homogeneous polysaccharide
      [abalone shell polysaccharide (ASP-1), corresponding to the first peak by size
      exclusion chromatography] and a non-polysaccharide compound [abalone shell
      compound (ACS-2), corresponding to the second peak by size exclusion
      chromatography], were extracted from the abalone (Haliotis discus hannai Ino)
      shell. We primarily focused on the investigation of ASP-1. As a
      heteropolysaccharide, ASP-1 is comprised of 9.3% uronic acid and 86.4%
      saccharide, the latter including mannose, ribose, rhamnose, glucose, galactose,
      arabinose, and two unknown monosaccharides, NO1 and NO2, with a mass ratio of
      9.5:10.1:2.2:18.2:21.8:5.5:16.5:16.2. The antioxidant activity assays indicated
      that 5.0 mg/mL ASP-1 has significant scavenging effects on superoxide radicals
      (86.2%) compared to the positive control of ascorbic acid (95.6%). 

PMID- 25062423
TI  - Genetic associations of the INSIG2 rs7566605 polymorphism with obesity-related
      metabolic traits in Malaysian Malays.
AB  - A genome-wide association study showed that the tagging single nucleotide
      polymorphism (SNP) rs7566605 in the insulin-induced gene 2 (INSIG2) was
      associated with obesity. Attempts to replicate this result in different
      populations have produced inconsistent findings. We aimed to study the
      association between the rs7566605 SNP with obesity and other metabolic parameters
      in Malaysian Malays. Anthropometric and obesity-related metabolic parameters and
      DNA samples were collected. We genotyped the rs7566605 polymorphism in 672
      subjects using real-time polymerase chain reaction. No significant associations
      were found between the rs7566605 tagging SNP of INSIG2 with obesity or other
      metabolic parameters in the Malaysian Malay population. The INSIG2 rs7566605 SNP
      may not play a role in the development of obesity-related metabolic traits in
      Malaysian Malays. 

PMID- 25062422
TI  - Association of chicken growth hormone polymorphisms with egg production.
AB  - Growth hormone (GH) has diverse functions in animals, together with other
      hormones from the somatotropic axis. Here, chicken GH (cGH) was investigated in
      recessive white chickens and Qingyuan partridge chickens as a candidate gene
      affecting egg production traits. Chicken egg production traits were studied in
      association with 4 selected single nucleotide polymorphisms (T185G, G662A,
      T3094C, and C3199T). Genotyping was performed by the polymerase chain reaction
      ligase detection reaction method. T185G was significantly associated with the egg
      production traits of body weight at first egg (BW), egg weight at first egg (EW),
      and the total egg production of 300-day old birds (EN 300). T3094C was also
      significantly associated with certain egg production traits; however, it affected
      the 2 breeds differently. Haplotypes of the 4 single nucleotide polymorphisms
      were also significantly associated with egg production traits of chicken age at
      first egg laying, BW, EW, and EN 300. H1H6 was the most advantageous diplotype
      for egg production. We putatively concluded that polymorphisms in the cGH gene
      and its haplotypes could be used as potential molecular markers for egg
      production traits to enhance the breeding programs of indigenous chickens. 

PMID- 25062424
TI  - A novel set of single-copy nuclear DNA markers for the genetic study of
      Salicaceae.
AB  - Species of Populus are widely distributed worldwide, playing a significant role
      in both ecology and economy. However, the lack of single-copy nuclear markers
      limits knowledge about the phylogeny and population genetics of this genus. In
      the present study, primer pairs of 15 single-copy nuclear markers were developed
      through bioinformatic methods based on complete genomic sequences of Populus
      trichocarpa and Salix arbutifolia. Twenty individuals of Populus davidiana Dode
      and Salix matsudana Koidz were used to evaluate the basic application of these
      markers with respect to marker length and diversity indices, respectively. The
      utility of single-copy nuclear markers is anticipated to facilitate further
      studies about the phylogeny, population genetics, and phylogeography of this
      genus, in addition to providing information about the evolutionary dynamics of
      Salicaceae. 

PMID- 25062425
TI  - Combined post-modification of iodide ligands and wide band gap ZnS in quantum dot
      sensitized solar cells.
AB  - Combined post-modification strategy of iodide ligands and wide band gap ZnS layer
      were employed in quantum dot sensitized solar cells. J-V curves show that the
      combined post-modification could improve the photoconversion efficiency compared
      to the single post-modification of ZnS because of the more effective passivation.
      CdS-sensitized and CdS/CdSe-co-sensitized solar cells both reveal that the
      assembly structure of QDs/I(-)/ZnS is more beneficial for the efficiency of solar
      cells than that of QDs/ZnS/I(-). EIS results show that the former structure
      exhibit higher interface resistance and could suppress electron recombination
      more powerfully. XPS results reveal that the iodide ligands have different
      binding energy, which indicates a different coordination state of the iodide atom
      in these two structures. Finally, 3.28% efficiency and 18.16 mA cm(-2) were
      achieved for CdS/CdSe QDSCs by applying this combined post-modification. 

PMID- 25062426
TI  - A new pro-prodrug aminoacid-based for trans-ferulic Acid and silybin intestinal
      release.
AB  - The aim of this work was the preparation and characterization of a pro-prodrug
      able to simultaneously transport silybin, a drug possessing various
      pharmacological effects, and trans-ferulic acid, a known antioxidant. More
      specifically, l-phenylalanine-N-(4-hydroxy-3-methoxy-phenyl) prop-2-en-O-(2R,3R)
      3,5,7-trihydroxy-2-((2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3
      dihydro-benzo-(1,4)-dioxin-6-yl)croman-4-one was synthesized by using the
      aminoacid l-phenylalanine (l-Phe) as carrier. Indeed, l-Phe is characterized by
      an intrinsic chemical reactivity due to the presence of an amino group, placed on
      the chiral center, and of a carboxylic group. The synthesis has been
      characterized first by adding silybin by means of carboxylic group and then, with
      the aim to confer antioxidant properties to this new carrier, by linking trans
      ferulic acid to l-Phe via amino group. The so obtained derivative was then
      characterized by FT-IR, and 1H-NMR spectroscopies. Furthermore, its ability to
      inhibit lipid peroxidation induced by tert-butyl hydroperoxide in rat liver
      microsomes, was evaluated. The 1,1-diphenyl-2-picrylhydrazyl radical-scavenging
      effect, was also assessed. The release of silybin and trans-ferulic acid was
      determined in simulated gastric and intestinal fluids over the time. The results
      showed that the covalent bond between both (i) silybin; or (ii) trans-ferulic
      acid and the amino acid was degraded by enzymatic reactions. In addition, the pro
      prodrug, showed strong antioxidant and scavenger activities. Due to these
      properties, this new pro-prodrug could be applied for the treatment of intestinal
      pathologies and it might improve the therapeutic potential of silybin which is
      strongly limited by its low solubility. 

PMID- 25062427
TI  - Zika virus infection after travel to Tahiti, December 2013.

PMID- 25062428
TI  - Role of migratory birds in spreading Crimean-Congo hemorrhagic fever, Turkey.
AB  - We investigated migratory birds' role in spreading Crimean-Congo hemorrhagic
      fever virus (CCHFV) through attached ticks. We detected CCHFV RNA in ticks on
      migratory birds in Turkey. Two isolates showed similarity with CCHFV genotype 4,
      suggesting a role for ticks in CCHFV epidemics in Turkey and spread of CCHFV by
      birds. 

PMID- 25062429
TI  - Is there an excess of significant findings in published studies of psychotherapy
      for depression?
AB  - BACKGROUND: Many studies have examined the efficacy of psychotherapy for major
      depressive disorder (MDD) but publication bias against null results may exist in
      this literature. However, to date, the presence of an excess of significant
      findings in this literature has not been explicitly tested. METHOD: We used a
      database of 1344 articles on the psychological treatment of depression,
      identified through systematic search in PubMed, PsycINFO, EMBASE and the Cochrane
      database of randomized trials. From these we identified 149 studies eligible for
      inclusion that provided 212 comparisons. We tested for an excess of significant
      findings using the method developed by Ioannidis and Trikalinos (2007), and
      compared the distribution of p values in this literature with the distribution in
      the antidepressant literature, where publication bias is known to be operating.
      RESULTS: The average statistical power to detect the effect size indicated by the
      meta-analysis was 49%. A total of 123 comparisons (58%) reported a statistically
      significant difference between treatment and control groups, but on the basis of
      the average power observed, we would only have expected 104 (i.e. 49%) to do so.
      There was therefore evidence of an excess of significance in this literature (p =
      0.010). Similar results were obtained when these analyses were restricted to
      studies including a cognitive behavioural therapy (CBT) arm. Finally, the
      distribution of p values for psychotherapy studies resembled that for published
      antidepressant studies, where publication bias against null results has already
      been established. CONCLUSIONS: The small average size of individual psychotherapy
      studies is only sufficient to detect large effects. Our results indicate an
      excess of significant findings relative to what would be expected, given the
      average statistical power of studies of psychotherapy for major depression.

PMID- 25062430
TI  - Distance and plasmon wavelength dependent fluorescence of molecules bound to
      silica-coated gold nanorods.
AB  - Plasmonic nanoparticles can strongly interact with adjacent fluorophores,
      resulting in plasmon-enhanced fluorescence or fluorescence quenching. This
      dipolar coupling is dependent upon nanoparticle composition, distance between the
      fluorophore and the plasmonic surface, the transition dipole orientation, and the
      degree of spectral overlap between the fluorophore's absorbance/emission and the
      surface plasmon band of the nanoparticles. In this work, we examine the distance
      and plasmon wavelength dependent fluorescence of an infrared dye ("IRDye") bound
      to silica-coated gold nanorods. Nanorods with plasmon band maxima ranging from
      530 to 850 nm are synthesized and then coated with mesoporous silica shells 11-26
      nm thick. IRDye is covalently attached to the nanoparticle surface via a click
      reaction. Steady-state fluorescence measurements demonstrate plasmon wavelength
      and silica shell thickness dependent fluorescence emission. Maximum fluorescence
      intensity, with approximately 10-fold enhancement, is observed with 17 nm shells
      when the nanorod plasmon maximum is resonant with IRDye absorption. Time-resolved
      photoluminescence reveals multiexponential decay and a sharp reduction in
      fluorescence lifetime with decreasing silica shell thickness and when the plasmon
      maximum is closer to IRDye absorption/emission. Control experiments are carried
      out to confirm that the observed changes in fluorescence are due to plasmonic
      interactions, is simply surface attachment. There is no change in fluorescence
      intensity or lifetime when IRDye is bound to mesoporous silica nanoparticles. In
      addition, IRDye loading is limited to maintain a distance between dye molecules
      on the surface to more than 9 nm, well above the Forster radius. This assures
      minimal dye-dye interactions on the surface of the nanoparticles. 

PMID- 25062431
TI  - Using discriminant analysis to determine sources of salinity in shallow
      groundwater prior to hydraulic fracturing.
AB  - High-volume hydraulic fracturing (HVHF) gas-drilling operations in the Marcellus
      Play have raised environmental concerns, including the risk of groundwater
      contamination. Fingerprinting water impacted by gas-drilling operations is not
      trivial given other potential sources of contamination. We present a multivariate
      statistical modeling framework for developing a quantitative, geochemical
      fingerprinting tool to distinguish sources of high salinity in shallow
      groundwater. The model was developed using new geochemical data for 204 wells in
      New York State (NYS), which has a HVHF moratorium and published data for
      additional wells in NYS and several salinity sources (Appalachian Basin brines,
      road salt, septic effluent, and animal waste). The model incorporates a
      stochastic simulation to predict the geochemistry of high salinity (>20 mg/L Cl)
      groundwater impacted by different salinity sources and then employs linear
      discriminant analysis to classify samples from different populations. Model
      results indicate Appalachian Basin brines are the primary source of salinity in
      35% of sampled NYS groundwater wells with >20 mg/L Cl. The model provides an
      effective means for differentiating groundwater impacted by basin brines versus
      other contaminants. Using this framework, similar discriminatory tools can be
      derived for other regions from background water quality data. 

PMID- 25062432
TI  - Intracellular Nef detected in peripheral blood mononuclear cells from HIV
      patients.
AB  - We report here the novel finding that HIV-negative factor (Nef) protein is
      present in considerable numbers of peripheral blood mononuclear cells (PBMCs)
      from viremic HIV-infected patients not on antiretroviral therapy (ART) and also
      in patients receiving virologically suppressive ART, though to a smaller degree.
      Interestingly, these Nef-positive PBMCs constitute predominantly uninfected
      bystander cells. These results may explain systemic pathology in HIV patients,
      even in those receiving ART.

PMID- 25062433
TI  - Chiral metallohelical complexes enantioselectively target amyloid beta for
      treating Alzheimer's disease.
AB  - Stereochemistry is a very important issue for the pharmaceutical industry and can
      determine drug efficacy. The design and synthesis of small molecules, especially
      chiral molecules, which selectively target and inhibit amyloid-beta (Abeta)
      aggregation, represent valid therapeutic strategies for treatment of Alzheimer's
      disease (AD). Herein we report that two triple-helical dinuclear
      metallosupramolecular complexes can act as a novel class of chiral amyloid-beta
      inhibitors. Through targeting alpha/beta-discordant stretches at the early steps
      of aggregation, these metal complexes can enantioselectively inhibit Abeta
      aggregation, which is demonstrated using fluorescent living cell-based screening
      and multiple biophysical and biochemical approaches. To the best of our
      knowledge, this is the first report of enantioselective inhibition of Abeta
      aggregation. Intriguingly, as a promising candidate for AD treatment, the chiral
      metal complex can cross the blood-brain barrier and have superoxide dismutase
      activity. It is well-known that chiral discrimination is important for
      understanding chiral drug action. Generally, one enantiomer is pharmaceutically
      active while the other is inactive or exerts severe side effects. Chiral
      discrimination should be important for AD treatment. Our work provides new
      insights into chiral inhibition of Abeta aggregation and opens a new avenue for
      design and screening of chiral agents as Abeta inhibitors against AD. 

PMID- 25062434
TI  - How does the quality of phospholipidosis data influence the predictivity of
      structural alerts?
AB  - The ability of drugs to induce phospholipidosis (PLD) is linked directly to their
      molecular substructures: hydrophobic, cyclic moieties with hydrophilic,
      peripheral amine groups. These structural properties can be captured and coded
      into SMILES arbitrary target specification (SMARTS) patterns. Such structural
      alerts, which are capable of identifying potential PLD inducers, should ideally
      be developed on a relatively large but reliable data set. We had previously
      developed a model based on SMARTS patterns consisting of 32 structural fragments
      using information from 450 chemicals. In the present study, additional PLD
      structural alerts have been developed based on a newer and larger data set
      combining two data sets published recently by the United States Food and Drug
      Administration (US FDA). To assess the predictive performance of the updated
      SMARTS model, two publicly available data sets were considered. These data sets
      were constructed using different criteria and hence represent different standards
      for overall quality. In the first data set high quality was assured as all
      negative chemicals were confirmed by the gold standard method for the detection
      of PLD-transmission electron microscopy (EM). The second data set was constructed
      from seven previously published data sets and then curated by removing compounds
      where conflicting results were found for PLD activity. Evaluation of the updated
      SMARTS model showed a strong, positive correlation between predictive performance
      of the alerts and the quality of the data set used for the assessment. The
      results of this study confirm the importance of using high quality data for
      modeling and evaluation, especially in the case of PLD, where species, tissue,
      and dose dependence of results are additional confounding factors. 

PMID- 25062435
TI  - Severe murine typhus with pulmonary system involvement.
AB  - We encountered a case of severe murine typhus complicated by acute respiratory
      distress syndrome. To determine worldwide prevalence of such cases, we reviewed
      the literature and found that respiratory symptoms occur in ~30% of murine typhus
      patients. In disease-endemic areas, murine typhus should be considered for
      patients with respiratory symptoms and fever. 

PMID- 25062437
TI  - Scleral imbrication combined with vitrectomy and gas tamponade for refractory
      macular hole retinal detachment associated with high myopia.
AB  - PURPOSE: To evaluate scleral imbrication with vitrectomy and gas tamponade for
      refractory macular hole retinal detachment associated with high myopia. METHODS:
      We retrospectively reviewed the medical records of eight eyes with macular hole
      retinal detachment and high myopia treated with temporal scleral imbrication,
      pars plana vitrectomy, and gas tamponade for refractory macular hole retinal
      detachment with history of pars plana vitrectomy. Retinal reattachment and
      macular hole closure were assessed. Postoperative changes in axial length and
      surgically induced astigmatism were evaluated. RESULTS: The retinas were
      reattached in all eyes and the macular holes closed in 6 (75%) eyes. The mean
      baseline logarithm of the minimum angle of resolution best-corrected visual
      acuity of 1.43 +/- 0.48 significantly (P < 0.01) improved to 0.87 +/- 0.34 at the
      final visit (889 +/- 173 postoperative days). The mean baseline axial length of
      29.5 +/- 1.3 mm decreased significantly (P < 0.01) to 27.1 +/- 1.9 mm 1 month
      after scleral imbrication and 28.1 +/- 1.7 mm at the final visit (P < 0.05 vs.
      baseline, P = 0.13 vs. 1 month). The mean 1-month surgically induced astigmatism
      of 3.6 +/- 1.4 diopters (D) after scleral imbrication significantly (P < 0.05)
      decreased to 2.4 +/- 1.5 D at the final visit. CONCLUSION: Scleral imbrication
      with vitrectomy and gas tamponade resulted in high reattachment and macular hole
      closure rates for treating refractory macular hole retinal detachment.

PMID- 25062436
TI  - Ligand binding and activation of PPARgamma by Firemaster(r) 550: effects on
      adipogenesis and osteogenesis in vitro.
AB  - BACKGROUND: The use of alternative flame retardants has increased since the phase
      out of pentabromodiphenyl ethers (pentaBDEs). One alternative, Firemaster(r) 550
      (FM550), induces obesity in rats. Triphenyl phosphate (TPP), a component of
      FM550, has a structure similar to that of organotins, which are obesogenic in
      rodents. OBJECTIVES: We tested the hypothesis that components of FM550 are
      biologically active peroxisome proliferator-activated receptor gamma (PPARgamma)
      ligands and estimated indoor exposure to TPP. METHODS: FM550 and its components
      were assessed for ligand binding to and activation of human PPARgamma. Solvent
      mapping was used to model TPP in the PPARgamma binding site. Adipocyte and
      osteoblast differentiation were assessed in bone marrow multipotent mesenchymal
      stromal cell models. We estimated exposure of children to TPP using a screening
      level indoor exposure model and house dust concentrations determined previously.
      RESULTS: FM550 bound human PPARgamma, and binding appeared to be driven primarily
      by TPP. Solvent mapping revealed that TPP interacted with binding hot spots
      within the PPARgamma ligand binding domain. FM550 and its organophosphate
      components increased human PPARgamma1 transcriptional activity in a Cos7 reporter
      assay and induced lipid accumulation and perilipin protein expression in BMS2
      cells. FM550 and TPP diverted osteogenic differentiation toward adipogenesis in
      primary mouse bone marrow cultures. Our estimates suggest that dust ingestion is
      the major route of exposure of children to TPP. CONCLUSIONS: Our findings suggest
      that FM550 components bind and activate PPARgamma. In addition, in vitro exposure
      initiated adipocyte differentiation and antagonized osteogenesis. TPP likely is a
      major contributor to these biological actions. Given that TPP is ubiquitous in
      house dust, further studies are warranted to investigate the health effects of
      FM550.

PMID- 25062438
TI  - Poor responders to bevacizumab pharmacotherapy in age-related macular
      degeneration and in diabetic macular edema demonstrate increased risk for
      obstructive sleep apnea.
AB  - PURPOSE: To investigate the risk for obstructive sleep apnea (OSA) in patients
      with exudative age-related macular degeneration (AMD) or diabetic macular edema
      with poor response to anti-vascular endothelial growth factor therapy with
      bevacizumab (Avastin). METHODS: Age-related macular degeneration group was
      categorized into nonexudative, exudative, or poor response exudative. Diabetic
      macular edema group included patients with nonproliferative diabetic retinopathy
      and cystoid macular edema. Patients were categorized based on the number of
      intravitreal injections of bevacizumab received. Both groups were compared with
      age-matched controls. Patients completed a screening questionnaire to assess the
      risk for OSA, the main outcome measure. RESULTS: Of 103 patients with AMD, 56
      (54.37%) had nonexudative AMD and 47 (45.63%) had exudative AMD, of which 14
      (29.79%) had poor response exudative AMD and were at a significantly higher risk
      of OSA (P < 0.05). Of 30 diabetic macular edema patients with cystoid macular
      edema, 4 (19%) received 1 injection, 18 (81.82%) received 2 or more consecutive
      injections, and 16 (72.73%) received 3 or more consecutive injections. Risk for
      OSA increased significantly with increasing number of injections (P < 0.05).
      CONCLUSION: Patients with exudative AMD and diabetic macular edema with poor
      response to anti-vascular endothelial growth factor therapy have a significantly
      higher risk of OSA compared with age-matched controls and should be screened to
      assess the risk of OSA.

PMID- 25062439
TI  - A false color fusion strategy for drusen and geographic atrophy visualization in
      optical coherence tomography images.
AB  - PURPOSE: To display drusen and geographic atrophy (GA) in a single projection
      image from three-dimensional spectral domain optical coherence tomography images
      based on a novel false color fusion strategy. METHODS: We present a false color
      fusion strategy to combine drusen and GA projection images. The drusen projection
      image is generated with a restricted summed-voxel projection (axial sum of the
      reflectivity values in a spectral domain optical coherence tomography cube,
      limited to the region where drusen is present). The GA projection image is
      generated by incorporating two GA characteristics: bright choroid and thin retina
      pigment epithelium. The false color fusion method was evaluated in 82 three
      dimensional optical coherence tomography data sets obtained from 7 patients, for
      which 2 readers independently identified drusen and GA as the gold standard. The
      mean drusen and GA overlap ratio was used as the metric to determine accuracy of
      visualization of the proposed method when compared with the conventional summed
      voxel projection, (axial sum of the reflectivity values in the complete spectral
      domain optical coherence tomography cube) technique and color fundus photographs.
      RESULTS: Comparative results demonstrate that the false color image is more
      effective in displaying drusen and GA than summed-voxel projection and CFP. The
      mean drusen/GA overlap ratios based on the conventional summed-voxel projection
      method, color fundus photographs, and the false color fusion method were
      6.4%/100%, 64.1%/66.7%, and 85.6%/100%, respectively. CONCLUSION: The false color
      fusion method was more effective for simultaneous visualization of drusen and GA
      than the conventional summed-voxel projection method and color fundus
      photographs, and it seems promising as an alternative method for visualizing
      drusen and GA in the retinal fundus, which commonly occur together and can be
      confusing to differentiate without methods such as this proposed one.

PMID- 25062440
TI  - Distribution of intraretinal exudates in diabetic macular edema during anti
      vascular endothelial growth factor therapy observed by spectral domain optical
      coherence tomography and fundus photography.
AB  - PURPOSE: To evaluate changes in the distribution and morphology of intraretinal
      microexudates and hard exudates (HEs) during intravitreal anti-vascular
      endothelial growth factor therapy in patients with persistent diabetic macular
      edema. METHODS: Twenty-four patients with persistent diabetic macular edema after
      photocoagulation were investigated in this prospective cohort study. Each eye was
      assigned to a loading dose of three anti-vascular endothelial growth factor
      treatments at monthly intervals. Additional single treatments were performed if
      diabetic macular edema persisted or recurred. Intraretinal exudates were analyzed
      over 6 months using spectral domain optical coherence tomography (SD-OCT) and
      fundus photography. RESULTS: Before treatment, microexudates were detected by SD
      OCT as hyperreflective foci in 24 eyes, whereas HEs were seen in 22 eyes. During
      therapy, HE increased significantly in number and size. This was accompanied by
      accumulation of microexudates in the outer retina. Enlargement of hyperreflective
      structures in SD-OCT was accompanied by enlargement of HE at corresponding fundus
      locations. A rapid reduction in diabetic macular edema was seen in all patients,
      but to varying degrees. Patients with hemoglobin A1c levels <7% and serum
      cholesterol <200 mg/dL formed fewer HEs and featured more edema reduction and
      visual acuity gain. CONCLUSION: Diabetic macular edema reduction during
      intravitreal anti-vascular endothelial growth factor therapy was accompanied by
      dynamic rearrangement of intraretinal exudates at corresponding locations in
      fundus photography and SD-OCT. Intraretinal aggregates of microexudates
      detectable as hyperreflective foci by SD-OCT may compose and precede HE before
      they become clinically visible.

PMID- 25062441
TI  - Foveal microstructure in macular holes surgically closed by inverted internal
      limiting membrane flap technique.
AB  - PURPOSE: To evaluate reconstructive foveal anatomical change in surgically closed
      macular hole (MH) by pars plana vitrectomy with inverted internal limiting
      membrane flap technique. METHODS: Spectral domain optical coherence tomography
      was used to evaluate foveal microstructures in 20 eyes of 19 patients who
      underwent pars plana vitrectomy with inverted internal limiting membrane flap
      technique to achieve MH closure. Eyes had idiopathic large MH with a diameter
      >500 MUm (n = 7), MH in high myopia (axial length >26.5 mm) without retinal
      detachment (RD; n = 7), and with RD caused by the MH (n = 6). RESULTS: The 6
      month postoperative spectral domain optical coherence tomography examination
      revealed restoration of the inner segment and outer segment junction in 3 of 7
      idiopathic large MH eyes (43%), 2 of 7 highly myopic MH eyes without RD (29%),
      and 1 of 6 highly myopic MH eyes with RD (17%), and detected the external
      limiting membrane in 4 of 7 idiopathic large MH eyes (57%), 3 of 7 highly myopic
      MH eyes without RD (43%), 1 of 6 highly myopic MH eyes with RD (17%). CONCLUSION:
      Inverted internal limiting membrane flap technique results in more satisfactory
      anatomical improvements in patients with idiopathic large MH eyes and highly
      myopic MH eyes without RD than with highly myopic MH eyes with RD. This might
      suggest that the foveal photoreceptor layer in MH with RD is destroyed and not
      recoverable even after retinal reattachment with surgical closure of the MH.

PMID- 25062442
TI  - Behavior and EEG concordance of active and quiet sleep in preterm very low birth
      weight and full-term neonates at matched conceptional age.
AB  - BACKGROUND: Sleep organization in neonates is an established predictor of
      neurological outcome and can be evaluated through the concordance between EEG and
      behavioral parameters. AIMS: To evaluate the correlation between sleep stages and
      behavioral states in neonates. STUDY DESIGN: Longitudinal study performed in a
      birth-cohort of preterm low birth weight neonates. SUBJECTS: Twenty five
      neonates, 15 preterm (gestational age between 27 and 33 weeks) and low birth
      weight (800-1500g) and 10 full-term neonates that served as controls. MEASURES:
      All neonates were submitted to video-electroencephalography of, at least, 60
      minute duration. The preterm during the first 15 days of life and, subsequently,
      at 38-42 weeks of conceptional age. The full-term between the 1st and 2nd days of
      life. The characterization of sleep stages by EEG parameters and behavioral
      states (based on Prechtl scale) was performed independently by previously trained
      researchers. RESULTS: Active sleep (AS) was the predominant sleep stage in the
      three groups. Preterm neonates had an increase in concordance between state 1 and
      quiet sleep (QS) from the 1st to the 2nd EEG (p<0.001), however in both
      observations it remained inferior when compared to state 2 and AS (p<0.001).
      Concordance between AS and state 2 was similar (p=0.567). CONCLUSIONS:
      Concordance between EEG and behavior is lower in QS in preterm and full-term
      neonates when compared to AS. Extra-uterine development of preterm neonates seems
      to accelerate concordance in QS. Prechtl behavior scale proved to be useful in
      preterm as percentage of concordance was similar in AS in the groups studied.

PMID- 25062443
TI  - These are not the k-mers you are looking for: efficient online k-mer counting
      using a probabilistic data structure.
AB  - K-mer abundance analysis is widely used for many purposes in nucleotide sequence
      analysis, including data preprocessing for de novo assembly, repeat detection,
      and sequencing coverage estimation. We present the khmer software package for
      fast and memory efficient online counting of k-mers in sequencing data sets.
      Unlike previous methods based on data structures such as hash tables, suffix
      arrays, and trie structures, khmer relies entirely on a simple probabilistic data
      structure, a Count-Min Sketch. The Count-Min Sketch permits online updating and
      retrieval of k-mer counts in memory which is necessary to support online k-mer
      analysis algorithms. On sparse data sets this data structure is considerably more
      memory efficient than any exact data structure. In exchange, the use of a Count
      Min Sketch introduces a systematic overcount for k-mers; moreover, only the
      counts, and not the k-mers, are stored. Here we analyze the speed, the memory
      usage, and the miscount rate of khmer for generating k-mer frequency
      distributions and retrieving k-mer counts for individual k-mers. We also compare
      the performance of khmer to several other k-mer counting packages, including
      Tallymer, Jellyfish, BFCounter, DSK, KMC, Turtle and KAnalyze. Finally, we
      examine the effectiveness of profiling sequencing error, k-mer abundance
      trimming, and digital normalization of reads in the context of high khmer false
      positive rates. khmer is implemented in C++ wrapped in a Python interface, offers
      a tested and robust API, and is freely available under the BSD license at
      github.com/ged-lab/khmer. 

PMID- 25062444
TI  - Impact of UV-B on drought- or cadmium-induced changes in the fatty acid
      composition of membrane lipid fractions in wheat.
AB  - UV-B radiation may have either a positive or negative impact under the same
      conditions in wheat, depending on the type of secondary abiotic stressor: Cd or
      drought. Supplemental UV-B prevented the wilting and leaf rolling induced by PEG
      treatment. In contrast, combined UV-B and Cd treatment resulted in pronounced
      oxidative stress. The opposite effect of UV-B radiation in the case of drought or
      cadmium stress may be related to the alteration induced in the fatty acid
      composition. UV-B caused changes in the unsaturation of leaf phosphatidylglycerol
      fractions, and the accumulation of flavonoid in the leaves may prevent the stress
      induced by subsequent drought treatment. However it resulted in pronounced injury
      despite the increased flavonoid content in roots exposed to Cd. This was
      manifested in a drastic decrease in the unsaturation of the leaf
      monogalactosyldiacylglycerol and the root phosphatidylglycerol and
      digalactosyldiacylglycerol fractions. Data on the flavonoid content and fatty
      acid composition showed that oxidative stress was induced by drought in the
      leaves, by Cd in the roots, and interestingly, by UV-B radiation in both the
      leaves and roots. The additive effect of the combined stresses was also detected
      in the roots. The results presented here suggest a relationship between the
      capacity of the plant to remodel the fatty acid composition and its resistance to
      various stress factors. 

PMID- 25062445
TI  - Cloning and expression of ophB gene encoding organophosphorus hydrolase from
      endophytic Pseudomonas sp. BF1-3 degrades organophosphorus pesticide
      chlorpyrifos.
AB  - Chlorpyrifos is an organophosphate pesticide that has adverse effect on animals
      and plants. We isolated endophytic bacterial strain, Pseudomonas sp. BF1-3, from
      balloon flower root which can hydrolyze chlorpyrifos. A gene (ophB) encoding a
      protein involved in chlorpyrifos degradation from this strain was cloned into
      Escherichia coli DH5alpha for confirming enzyme activity. After sequencing, total
      1024bp nucleotide sequences were found in the open reading frame of ophB. The
      chlorpyrifos degradation patterns by E. coli DH5alpha (ophB) were observed.
      During incubation in minimal salt (M9) medium supplemented with chlorpyrifos
      (100mgL(-1)), the E. coli DH5alpha harboring ophB degraded about 97% initial
      chlorpyrifos (100mgL(-1)) and accumulated 86mgL(-1) 3,5,6-trichloro-2-pyridinol
      (TCP) within 9 days. In addition, optical density (OD) of E. coli DH5alpha (ophB)
      culture at 600nm was increased from 0.172 to 1.118 within 2 days of inoculation
      in the chlorpyrifos supplemented M9 medium. The estimated molecular weight of
      purified OphB protein was determined to be 31.4kDa by SDS-PAGE. The OphB enzyme
      was most active at pH 8 and an optimal temperature around 35 degrees C. These
      results indicate that endophytic bacteria are supposed to be useful for
      biological control of environments contaminated with pesticides. 

PMID- 25062446
TI  - Effects of atrazine and chlorpyrifos on DNA methylation in the liver, kidney and
      gill of the common carp (Cyprinus carpio L.).
AB  - Pesticide exposure has repeatedly been associated with cancers, although the
      molecular mechanisms behind this association are largely undetermined. Abnormal
      DNA methylation plays a key role in the process of some disease. However, little
      was known about the effect of pesticides on DNA methylation in the common carp.
      In this study, we investigated the mRNA levels of DNA methyltransferases (DNMTs)
      and methyl-CpG-binding protein DNA-binding domain protein 2 (MBD2) as well as the
      DNA methylation levels in the liver, kidney and gill of the common carp (Cyprinus
      carpio L.) after 40-d exposure to atrazine (ATR) and chlorpyrifos (CPF) alone or
      in combination, and a 40-d recovery period. Juvenile common carp were exposed to
      various concentrations of ATR (at concentrations of 4.28, 42.8 and 428MUg/L), CPF
      (1.16, 11.6 and 116MUg/L), and an ATR/CPF mixture (at concentrations of 1.13,
      11.3 and 113MUg/L). The results revealed that the levels of genomic DNA
      methylation decreased in all tissues after 40d of exposure to ATR and CPF either
      individually or in combination. Moreover, the mRNA expression of DNMTs was down
      regulated in all treatment groups. In contrast, the mRNA expression of MBD2 was
      up-regulated. These results demonstrated that long-term exposure to ATR, CPF and
      ATR/CPF mixtures could disrupt genomic DNA. It might imply that DNA methylation
      is involved in the toxicity caused by ATR and CPF in the common carp. 

PMID- 25062447
TI  - Qualitative toxicity assessment of silver nanoparticles on the fresh water
      bacterial isolates and consortium at low level of exposure concentration.
AB  - Silver nanoparticles (AgNPs) pose a high risk of exposure to the natural
      environment owing to their extensive usage in various consumer products. In the
      present study we attempted to understand the harmful effect of AgNPs at
      environmentally relevant low concentration levels (<=1ppm) towards two different
      freshwater bacterial isolates and their consortium. The standard plate count
      assay suggested that the AgNPs were toxic towards the fresh water bacterial
      isolates as well as the consortium, though toxicity was significantly reduced for
      the cells in the consortium. The oxidative stress assessment and membrane
      permeability studies corroborated with the toxicity data. The detailed electron
      microscopic studies suggested the cell degrading potential of the AgNPs, and the
      FT-IR studies confirmed the involvement of the surface groups in the toxic
      effects. No significant ion leaching from the AgNPs was observed at the applied
      concentration levels signifying the dominant role of the particle size, and size
      distribution in bacterial toxicity. The reduced toxicity for the cells in the
      consortium than the individual isolates has major significance in further studies
      on the ecotoxicity of the AgNPs. 

PMID- 25062448
TI  - Comparison of 3% sorbitol vs psyllium fibre as oral contrast agents in MR
      enterography.
AB  - OBJECTIVE: To compare the degree of small bowel distension achieved by 3%
      sorbitol, a high osmolarity solution, and a psyllium-based bulk fibre as oral
      contrast agents (OCAs) in MR enterography (MRE). METHODS: This retrospective
      study was approved by our institutional review board. A total of 45 consecutive
      normal MRE examinations (sorbitol, n = 20; psyllium, n = 25) were reviewed. The
      patients received either 1.5 l of 3% sorbitol or 2 l of 1.6 g kg(-1) psyllium
      prior to imaging. Quantitative small bowel distension measurements were taken in
      five segments: proximal jejunum, distal jejunum, proximal ileum, distal ileum and
      terminal ileum by two independent radiologists. Distension in these five segments
      was also qualitatively graded from 0 (very poor) to 4 (excellent) by two
      additional independent radiologists. Statistical analysis comparing the groups
      and assessing agreement included intraclass coefficients, Student's t-test and
      Mann-Whitney U-test. RESULTS: Small bowel distension was not significantly
      different in any of the five small bowel segments between the use of sorbitol and
      psyllium as OCAs in both the qualitative (p = 0.338-0.908) and quantitative
      assessments (p = 0.083-0.856). The mean bowel distension achieved was 20.1 +/-
      2.2 mm for sorbitol and 19.8 +/- 2.5 mm for psyllium (p = 0.722). Visualization
      of the ileum was good or excellent in 65% of the examinations in both groups.
      CONCLUSION: Sorbitol and psyllium are not significantly different at distending
      the small bowel and both may be used as OCAs for MRE studies. ADVANCES IN
      KNOWLEDGE: This is the first study to directly compare the degree of distension
      in MRE between these two common, readily available and inexpensive OCAs.

PMID- 25062449
TI  - Mechanochemical synthesis of bumetanide-4-aminobenzoic acid molecular cocrystals:
      a facile and green approach to drug optimization.
AB  - Molecular cocrystals are of growing interest in pharmaceutics for their improved
      physicochemical properties. Their mechanochemical synthesis is very promising,
      being easy, cheap, and "green". Here, for the first time, we report on
      cocrystallization of bumetanide, a diuretic and natriuretic active principle, and
      4-aminobenzoic acid. The synthesis is performed both by wet and dry grinding. The
      cocrystal formation was investigated with a wide range of techniques, including
      solid-state NMR, IR, XRD, microscopy, and thermal analysis. Wet and dry grinding
      procedures led to different cocrystal polymorphs. In particular, the dry method
      gave a cocrystal by powder amorphization and subsequent crystallization. DFT
      calculations at the B3LYP/6-31+G(d,p) level of theory shed light on the H-bond
      scheme at the basis of cocrystal formation. The cocrystals showed improved
      solubility and dissolution rate with respect to the drug alone. This could
      guarantee a faster absorption and a better bioavailability of the active
      principle. 

PMID- 25062450
TI  - Potential of methyl fluoride as a universal reaction gas to overcome spectral
      interference in the determination of ultratrace concentrations of metals in
      biofluids using inductively coupled plasma-tandem mass spectrometry.
AB  - Methyl fluoride (a mixture of 10% CH3F and 90% of He) was evaluated as a reaction
      gas in inductively coupled plasma-tandem mass spectrometry (ICPMS/MS) in the
      context of the determination of ultratrace concentrations of medically relevant
      metals (Al, Co, Cr, Mn, Ni, Ti, and V) in blood serum and urine. Via product ion
      scanning, whereby only ions of the mass-to-charge ratio of the target nuclide
      were admitted into the octopole reaction cell, the various reaction product ions
      formed for each of the target elements were identified at different CH3F gas flow
      rates. Limits of detection (LODs) and of quantification (LOQs) and linearity of
      the calibration curve were documented under (i) optimized ICPMS/MS conditions for
      single-element monitoring and (ii) compromise conditions, allowing for
      multielement determination. Even under compromise settings, instrumental LODs
      were below 10 ng/L for all target elements, while the use of CH3F provided
      interference-free conditions for their determination in the biofluids of
      interest. Quantitative data obtained for Seronorm blood serum and urine reference
      materials were in excellent agreement with the corresponding reference values
      and/or results obtained using double-focusing sector-field ICPMS (for those
      elements for which no certified values were available or that were affected
      during reconstitution), proving the potential of this reaction gas for
      multielement ultratrace analysis via ICPMS/MS. 

PMID- 25062451
TI  - Effects of recombinant activins on steroidogenesis in human granulosa-lutein
      cells.
AB  - CONTEXT: Exerting a broad range of biological effects in various tissues,
      activins are homo- or heterodimers of activin/inhibin beta-subunits (betaA,
      betaB, betaC, and betaE in humans). Although activins A (betaAbetaA), B
      (betaBbetaB), AB (betaAbetaB), and AC (betaAbetaC) have been demonstrated in the
      female reproductive system, little is known about their individual functions in
      the ovary. OBJECTIVE: To investigate the biological roles and activities of
      activins in regulating steroidogenesis in human granulosa cells. DESIGN: Human
      granulosa-lutein cells obtained from 32 patients undergoing in vitro
      fertilization were used to investigate the effects of activin A, B, AB, and AC on
      the expression of steroidogenic enzymes and steroid production. SETTING: An
      academic research center. MAIN OUTCOME MEASURES: mRNA and protein levels were
      examined by reverse transcription quantitative real-time PCR and Western blot
      analysis, respectively. The production of estradiol and progesterone was measured
      by enzyme immunoassay. RESULTS: P450 aromatase, FSH receptor, and estradiol
      levels were increased, whereas steroidogenic acute regulatory protein (StAR), LH
      receptor, and progesterone levels were decreased after treatment with activin A,
      B, and AB, but not activin AC. FSH or LH induced the production of
      aromatase/estradiol and StAR/progesterone; however, pretreatment with activin A,
      B, or AB enhanced the effects of gonadotropins on aromatase/estradiol, but
      suppressed their effects on StAR/progesterone. Treatment with activin A, B, or AB
      induced the phosphorylation of SMA- and MAD-related proteins (SMAD2 and 3),
      whereas activin AC had no such effects. Furthermore, co-culture of activin AC (1
      100 ng/mL) with activin A (25 ng/mL) did not alter the effects of activin A on
      P450 aromatase or StAR mRNA levels. CONCLUSION: Activin A, B, and AB have similar
      effects on steroidogenesis in human granulosa cells. In contrast, activin AC is
      not biologically active and does not act as a competitive antagonist.

PMID- 25062452
TI  - Exome sequencing reveals SYCE1 mutation associated with autosomal recessive
      primary ovarian insufficiency.
AB  - CONTEXT: Primary ovarian insufficiency (POI) is caused by ovarian follicle
      depletion or follicle dysfunction. The phenotypic spectrum ranges from absence of
      pubertal maturation to early menopause. Genes involved in essential steps in
      chromosome synapsis and recombination during meiosis, such as synaptonemal
      complex central element 1 (SYCE1), have been shown to cause POI in animal models.
      We describe for the first time a homozygous mutation in SYCE1 in humans.
      OBJECTIVE: To identify the genetic cause of POI in an Israeli Arab family with a
      consanguineous pedigree. SETTING AND DESIGN: A family-based genetic study
      conducted at a tertiary medical center. PATIENTS: Two daughters of consanguineous
      parents (first cousins) from a 13-member family were diagnosed with POI.
      Genotyping was performed in the index patients, their parents, and four
      unaffected siblings. INTERVENTION: DNA from the affected sisters was subjected to
      whole-exome sequencing. The genotypes of interest were confirmed and genotypes of
      the additional family members were determined by Sanger sequencing. Genotyping
      was also performed in 90 ethnically matched control individuals. RESULTS: A
      nonsense homozygous mutation (c.613C>T) was identified in the SYCE1 gene in both
      affected sisters. The parents and three brothers were heterozygous for the
      mutation, and an unaffected sister did not carry the mutation. The mutation was
      not identified in the DNA samples from the 90 control subjects. CONCLUSIONS:
      Given the known function of the SYCE1 gene, we suggest that the nonsense mutation
      identified accounts for the POI phenotype. These results highlight the importance
      of the synaptonemal complex and meiosis in ovarian function.

PMID- 25062453
TI  - McCune-Albright syndrome: a detailed pathological and genetic analysis of disease
      effects in an adult patient.
AB  - CONTEXT: McCune Albright syndrome (MAS) is a clinical association of endocrine
      and nonendocrine anomalies caused by postzygotic mutation of the GNAS1 gene,
      leading to somatic activation of the stimulatory alpha-subunit of G protein
      (Gsalpha). Important advances have been made recently in describing pathological
      characteristics of many MAS-affected tissues, particularly pituitary, testicular,
      and adrenal disease. Other rarer disease related features are emerging.
      OBJECTIVE: The objective of the investigation was to study the pathological and
      genetic findings of MAS on a tissue-by-tissue basis in classically and
      nonclassically affected tissues. DESIGN: This was a comprehensive autopsy and
      genetic analysis. SETTING: The study was conducted at a tertiary referral
      university hospital. PATIENTS: An adult male patient with MAS and severe disease
      burden including gigantism was the subject of the study. INTERVENTION(S):
      Interventions included clinical, hormonal, and radiographic studies and gross and
      microscopic pathology analyses, conventional PCR, and droplet digital PCR
      analyses of affected and nonaffected tissues. MAIN OUTCOME MEASURE: Pathological
      findings and the presence of GNAS1 mutations were measured. RESULTS: The patient
      was diagnosed with MAS syndrome at 6 years of age based on the association of
      cafe-au-lait spots and radiological signs of polyostotic fibrous dysplasia.
      Gigantism developed and hyperprolactinemia, hypogonadotropic hypogonadism, and
      hyperparathyroidism were diagnosed throughout the adult period. The patient died
      at the age of 39 years from a pulmonary embolism. A detailed study revealed
      mosaiscism for the p.R201C GNAS1 mutation distributed across many endocrine and
      nonendocrine tissues. These genetically implicated tissues included rare or
      previously undescribed disease associations including primary hyperparathyroidism
      and hyperplasia of the thymus and endocrine pancreas. CONCLUSIONS: This
      comprehensive pathological study of a single patient highlights the complex
      clinical profile of MAS and illustrates important advances in understanding the
      characteristics of somatic GNAS1-related pathology across a wide range of
      affected organs.

PMID- 25062454
TI  - An increase in serum 25-hydroxyvitamin D concentrations preceded a plateau in
      type 1 diabetes incidence in Finnish children.
AB  - CONTEXT: In Finland the world-record for the highest incidence of type 1 diabetes
      has risen steeply over the past decades. However, after 2006 the incidence rate
      has plateaued. We showed earlier, that despite the strong genetic disease
      component, environmental factors are driving the increasing disease incidence.
      OBJECTIVE: Since vitamin D intake has increased considerably in the country since
      2003, we analyzed how serum 25-hydroxyvitamin D (25[OH]D) concentration changed
      over time in healthy children, and the timely relation of these changes to
      disease incidence. DESIGN, SETTING AND PARTICIPANTS: The birth cohort of the
      Finnish Type 1 Diabetes Prediction and Prevention project was used to explore
      longitudinal changes in serum 25-hydroxyvitamin concentrations. The sampling
      period was limited to children born from 1994 to 2004, with serum samples
      collected during 1998-2006 in the Turku area, Southwest Finland (60  degrees N).
      MAIN OUTCOME MEASURE: 25(OH)D concentrations were measured every 3-6 months from
      birth, ages ranging from 0.3 to 12.2 years (387 subjects, 5334 measurements).
      RESULTS: Serum 25(OH)D concentrations were markedly lower before 2003 than after
      (69.3 +/- 1.0 nmol/L vs 84.9 +/- 1.3 nmol/L, respectively, P < .001) in both
      genders. The mean difference between the periods was 15.7 +/- 1.3 nmol/L (P <
      .001). Importantly, the frequency of children with low serum 25(OH)D levels (< 50
      nmol/L) was reduced to almost half from 2003 (37.3% vs 69.9 %; P < .001).
      Similarly, severe vitamin D deficiency (<25 nmol/L) also decreased (2.7% vs 7.7%;
      P = .005). In addition, we detected higher 25(OH)D concentrations in young
      children (< 2 years) as compared to older children, which is explained by higher
      vitamin D intake in this group. CONCLUSIONS: We provide evidence that an increase
      in circulating concentrations of 25(OH)D shows a delayed temporal association
      with leveling off of type 1 diabetes incidence in Finland after 2006.

PMID- 25062456
TI  - Preoperative neck ultrasound in clinical node-negative differentiated thyroid
      cancer.
AB  - BACKGROUND: The impact of preoperative neck ultrasound (US) on management of the
      lateral neck in patients with differentiated thyroid cancer is unclear. The
      objective of this study was to assess the impact of preoperative neck US on the
      rate of lateral neck dissection in clinical N0 neck and initial response to
      therapy. METHODS: An institutional review board-approved retrospective review of
      890 patients that had thyroid surgery for differentiated thyroid cancer between
      2009 and 2010 was performed at our institution. Patients with palpable neck
      disease, distant metastases, less than total thyroidectomy, no postoperative
      thyroglobulin (Tg) determinations, and positive Tg antibodies were excluded,
      leaving 465 patients available for analysis. Patients were divided into those who
      had a preoperative neck US to evaluate lateral neck nodes (n = 234) and those who
      did not (n = 231). Patient and tumor characteristics were compared using the
      chi(2) test. The primary end point was response to therapy, defined by
      postoperative US and Tg levels. RESULTS: There were no significant differences in
      age, histology, T stage, postoperative radioactive iodine dose, American Joint
      Committee on Cancer stage, American Thyroid Association risk category, or
      duration of follow up between the 2 groups. Patients with preoperative neck US
      were more likely to have lateral neck dissection compared with patients without
      preoperative neck US [n = 31 (13.2%) vs n = 2 (0.9%); P < .001]. Preoperative
      neck US resulted in a better response to therapy (P = 0.005), a greater
      likelihood of no evidence of disease, and a smaller likelihood of having a
      biochemical or structural incomplete response or a return for delayed neck
      dissection. The preoperative US group also resulted in fewer recurrences; 10
      patients from the no preoperative US group returned to the operating room
      compared with two patients (4.3% vs 0.9%, P = .018) who had a preoperative neck
      US. CONCLUSION: Preoperative neck US detects more lateral neck disease, leading
      to an increase in lateral neck dissection with subsequent improvement in response
      to therapy and fewer return to the operating room for regional recurrence
      management.

PMID- 25062455
TI  - Obesity-associated melanocortin-4 receptor mutations are associated with changes
      in the brain response to food cues.
AB  - CONTEXT: Mutations in the melanocortin-4 receptor (MC4R) represent the commonest
      genetic form of obesity and are associated with hyperphagia. OBJECTIVE: The aim
      of this study was to investigate whether melanocortin signaling modulates
      anticipatory food reward by studying the brain activation response to food cues
      in individuals with MC4R mutations. Design/Setting/Participants/Main Outcome
      Measure: We used functional magnetic resonance imaging to measure blood oxygen
      level-dependent responses to images of highly palatable, appetizing foods, bland
      foods, and non-food objects in eight obese individuals with MC4R mutations, 10
      equally obese controls, and eight lean controls with normal MC4R genotypes. Based
      on previous evidence, we performed a region-of-interest analysis centered on the
      caudate/putamen (dorsal striatum) and ventral striatum. RESULTS: Compared to non
      foods, appetizing foods were associated with activation in the dorsal and ventral
      striatum in lean controls and in MC4R-deficient individuals. Surprisingly, we
      observed reduced activation of the dorsal and ventral striatum in obese controls
      relative to MC4R-deficient patients and lean controls. There were no group
      differences for the contrast of disgusting foods with bland foods or non-foods,
      suggesting that the effects observed in response to appetizing foods were not
      related to arousal. CONCLUSION: We identified differences in the striatal
      response to food cues between two groups of obese individuals, those with and
      those without MC4R mutations. These findings are consistent with a role for
      central melanocortinergic circuits in the neural response to visual food cues.

PMID- 25062457
TI  - BAG3 promoted starvation-induced apoptosis of thyroid cancer cells via
      attenuation of autophagy.
AB  - CONTEXT: BAG3 plays a regulatory role in a number of cellular processes. Recent
      studies have attracted much attention on its role in activation of selective
      autophagy. In addition, we have very recently reported that BAG3 is implicated in
      a BECN1-independent autophagy, namely noncanonical autophagy. OBJECTIVE: The
      current study aimed to investigate the potential involvement of BAG3 in canonical
      autophagy triggered by Earle's Balanced Salt Solution (EBSS) starvation. SETTING
      AND DESIGN: Replacement of complete medium with EBSS was used to trigger
      canonical autophagy. BAG3 expression was measured using real-time RT-PCR and
      Western blot. Autophagy was monitored using LC3-II transition and p62/SQSTM1
      accumulation by Western blot, as well as punctate distribution of LC3 by
      immunofluorescence staining. Cell growth and apoptotic cell death was
      investigated using real-time cell analyzer and flowcytometry, respectively.
      RESULTS: BAG3 expression was potently reduced by EBSS starvation. Forced
      expression of BAG3 suppressed autophagy and promoted apoptotic cell death of
      thyroid cancer cells elicited by starvation. In addition, in the presence of
      autophagy inhibitor, the enhancing effect of BAG3 on apoptotic cell death was
      attenuated. CONCLUSIONS: These results suggest that BAG3 promotes apoptotic cell
      death in starved thyroid cancer cells, at least in part by autophagy attenuation.

PMID- 25062458
TI  - Glucose-related arterial stiffness and carotid artery remodeling: a study in
      normal subjects and type 2 diabetes patients.
AB  - CONTEXT: Hyperglycemia is associated with a higher carotid intima-media thickness
      (IMT); however, it is not established whether this increase reflects early
      atherosclerotic changes or adaptive remodeling responding to hyperglycemia
      induced alteration in mechanical properties of the arterial wall. OBJECTIVE: The
      aims of this study were to compare carotid geometry and circumferential wall
      stress between patients with type 2 diabetes mellitus (T2DM) and healthy controls
      and to evaluate the associations between chronic glucose exposure and measures of
      arterial structure and function. DESIGN AND SETTING: This was a case-control and
      cross-sectional study within institutional practice. PARTICIPANTS: PARTICIPANTS
      included 133 T2DM patients free of cardiovascular complications and 133 healthy
      controls with normal glucose metabolism, matched for sex, age, and body mass
      index. MAIN OUTCOME MEASURES: Common carotid artery (CCA) IMT, luminal diameter,
      wave speed, and local pulse pressure (PP) were evaluated. RESULTS: As compared
      with controls, T2DM patients had higher (P < .0001) CCA IMT (640 +/- 81 vs 709 +/
      118 MUm), luminal diameter (6.12 +/- 0.67 vs 6.69 +/- 0.56 mm), and brachial PP
      (47 +/- 7 vs 57 +/- 12 mm Hg), whereas luminal radius to IMT ratio (4.8 +/- 0.7
      vs 4.8 +/- 0.8, P = .57) and circumferential wall stress (49.0 +/- 8.3 vs 50.6 +/
      10.3 kPa, P = .26) were comparable between the 2 groups. In T2DM patients,
      glycosylated hemoglobin was independently related to CCA wave speed and local PP,
      but not to IMT that was determined by age, local PP, and luminal diameter.
      CONCLUSIONS: This study suggests that the increase in IMT associated with a
      higher glucose exposure might reflect adaptive remodeling counteracting an
      increase in pulsatile strain and preventing increase in circumferential wall
      stress caused by luminal enlargement of stiff arteries.

PMID- 25062459
TI  - The effect of nutritional rickets on bone mineral density.
AB  - CONTEXT: Nutritional rickets is caused by impaired mineralization of growing
      bone. The effect of nutritional rickets on areal bone mineral density (aBMD) has
      not been established. OBJECTIVE: Our objective was to determine if aBMD is lower
      in children with active rickets than in healthy control children. We expected
      that the reduction in aBMD would vary between the radial and ulnar metaphyses
      near the growth plates and the proximal diaphyses. DESIGN: Case-control study.
      SETTING: Primary care outpatient department of a teaching hospital in Jos,
      Nigeria. PARTICIPANTS: Nigerian children with radiographically-confirmed rickets
      were compared with a reference group of control children without rickets from the
      same community. MAIN OUTCOME MEASURES: Forearm bone density measurements were
      performed in all children with pDXA. Age, sex, and height-adjusted bone density
      parameters were compared between children with rickets and control subjects.
      RESULTS: A total of 264 children with active rickets (ages 13-120 months) and 660
      control children (ages 11-123 months) were included. In multivariate analyses
      controlling for height, age, and gender, rickets was associated with a 4% greater
      bone area and 7% lower aBMD of the radial and ulnar metaphyses compared with
      controls (P < .001). The effects of rickets on the diaphyses of the radius and
      ulna were more pronounced with an 11% greater bone area, 21% lower aBMD, and 24%
      lower bone mineral apparent density than controls (P < .001). In children with
      rickets, aBMD values were unrelated to dairy product intake or serum calcium,
      phosphorus, alkaline phosphatase, or 25-hydroxyvitamin D. Metaphyseal aBMD was
      positively associated with radiographic severity score, attributed to bone edge
      detection artifact by densitometry in active rickets. CONCLUSION: Rickets results
      in increased bone area and reduced aBMD, which are more pronounced in the
      diaphyseal than in the metaphyseal regions of the radius and ulna, consistent
      with secondary hyperparathyroidism, generalized osteoid expansion and impaired
      mineralization.

PMID- 25062460
TI  - Cardiovascular and metabolic risk factors in inherited autoinflammation.
AB  - CONTEXT: The natural progression of metabolic abnormalities among patients with
      inherited autoinflammation is unclear. OBJECTIVE: The objective of the study was
      to assess the cardiometabolic risk of participants with familial Mediterranean
      fever (FMF). DESIGN AND SETTING: This study included nationwide cross-sectional
      and longitudinal cohorts. PARTICIPANTS: The prevalence of components of the
      metabolic syndrome at age 17 years was assessed from the medical database of the
      Israeli Defense Force from 1973 through 1997. Included were 745 males with FMF,
      902 healthy male siblings, and a control group of 787,714 participants. A
      prospective follow-up study traced the incidence of components of the metabolic
      syndrome to age 45 years among 57 FMF and 1568 control army personnel
      participants. INTERVENTIONS: Body mass index (BMI) and blood pressure (BP) were
      measured at age 17 years (cross-sectional); lifestyle, anthropometric, and
      biochemical data were periodically recorded from age 25 years. MAIN OUTCOME
      MEASURES: Abnormal BMI or BP (age 17 y) and Adult Treatment Panel III criteria of
      the metabolic syndrome were measured. RESULTS: In multivariable regression
      analysis adjusted for known confounders of obesity, FMF participants had an odds
      ratio of 0.65 for the occurrence of overweight [95% confidence interval (CI) 0.44
      0.96, P = .03] and 0.66 (95% CI 0.48-0.92, P = .012) for hypertension-range BP;
      their siblings tended to obesity (odds ratio 1.48; 95% CI 1.04-2.11, P = .008).
      In the follow-up arm, a multivariable analysis adjusted for age, birth year, BMI,
      education, socioeconomic status, ethnicity, and physical activity yielded hazard
      ratios of 0.32 (95% CI 0.10-0.82, P = .002) for incident obesity, 0.49 (95% CI
      0.25-0.95, P = .037) for incident triglycerides 150 mg/dL or greater, 0.56 (95%
      CI 0.31-0.98, P = .048) for low-density lipoprotein cholesterol 130 mg/dL or
      greater, and 2.14 (1.368-3.359, P = .001) for high-density lipoprotein
      cholesterol less than 40 mg/dL for FMF participants compared with controls.
      Incident elevated BP was lower among FMF participants (hazard ratio 0.49; 95% CI
      0.23-1.00, P = .05), whereas dysglycemia incidence was comparable. CONCLUSIONS:
      FMF is associated with lower rates of most components of the metabolic syndrome
      compared with normal subjects, unlike other inflammatory conditions.

PMID- 25062461
TI  - Comparison of hip geometry, strength, and estimated fracture risk in women with
      anorexia nervosa and overweight/obese women.
AB  - CONTEXT: Data suggest that anorexia nervosa (AN) and obesity are complicated by
      elevated fracture risk, but skeletal site-specific data are lacking. Traditional
      bone mineral density (BMD) measurements are unsatisfactory at both weight
      extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry
      data to estimate hip geometry and femoral strength. Factor of risk (phi) is the
      ratio of force applied to the hip from a fall with respect to femoral strength;
      higher values indicate higher hip fracture risk. OBJECTIVE: The objective of the
      study was to investigate hip fracture risk in AN and overweight/obese women.
      DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a
      Clinical Research Center. PATIENTS: PATIENTS included 368 women (aged 19-45 y):
      246 AN, 53 overweight/obese, and 69 lean controls. MAIN OUTCOME MEASURES: HSA
      derived femoral geometry, peak factor of risk for hip fracture, and factor of
      risk for hip fracture attenuated by trochanteric soft tissue (phi(attenuated))
      were measured. RESULTS: Most HSA-derived parameters were impaired in AN and
      superior in obese/overweight women vs controls at the narrow neck,
      intertrochanteric, and femoral shaft (P <= .03). The phi(attenuated) was highest
      in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated
      with superior, and duration of amenorrhea with inferior, HSA-derived parameters
      and phi(attenuated) (P < .05). Mean phi(attenuated) (P = .036), but not femoral
      neck BMD or HSA-estimated geometry, was impaired in women who had experienced
      fragility fractures. CONCLUSIONS: Femoral geometry by HSA, hip BMD, and factor of
      risk for hip fracture attenuated by soft tissue are impaired in AN and superior
      in obesity, suggesting higher and lower hip fracture risk, respectively. Only
      attenuated factor of risk was associated with fragility fracture prevalence,
      suggesting that variability in soft tissue padding may help explain site-specific
      fracture risk not captured by BMD.

PMID- 25062462
TI  - Lack of FGF23 response to acute changes in serum calcium and PTH in humans.
AB  - CONTEXT: 1,25-Dihydroxyvitamin D (1,25D) administration and long-term increases
      in phosphate, PTH, and calcium concentrations are associated with increases in
      circulating fibroblast growth factor 23 (FGF23); however, whether or not acute
      changes in serum calcium modulate short-term FGF23 release is unknown.
      OBJECTIVE/DESIGN: To assess the direct effect of acute changes in calcium and PTH
      on circulating FGF23 levels. SETTING: A university clinical and translational
      research center. PATIENTS/PARTICIPANTS: Twelve healthy volunteers and 10 dialysis
      patients. INTERVENTIONS: Calcium gluconate and sodium citrate were infused for
      120 minutes on 2 consecutive days. MAIN OUTCOME MEASURES: Serum levels of ionized
      calcium, phosphorus, PTH, 1,25D, and plasma C-terminal FGF23 levels were obtained
      at 0, 13, 30, 60, 90, and 120 minutes during the infusions. RESULTS: During the
      calcium infusion, serum calcium concentrations increased from 1.33 +/- 0.01 to
      1.57 +/- 0.04 mmol/L (P < .05 from baseline) and from 1.20 +/- 0.05 to 1.50 +/-
      0.03 mmol/L (P < .05 from baseline) in healthy subjects and in dialysis patients,
      respectively, whereas serum calcium values decreased from 1.33 +/- 0.01 to 1.03
      +/- 0.02 mmol/L (P < .05 from baseline) and from 1.26 +/- 0.04 to 1.07 +/- 0.03
      mmol/L (P < .05 from baseline) in the two groups, respectively during the sodium
      citrate infusion. PTH levels decreased from 35 (29, 57) to 8 (2,10) pg/mL
      (healthy subjects) (P < .05 from baseline) and from 292 (109, 423) to 44 (28, 86)
      pg/mL (dialysis patients) (P < .05 from baseline) during the calcium infusion and
      rose from 31 (25, 56) to 122 (95, 157) pg/mL and from 281 (117, 607) to 468 (169,
      928) pg/mL (P < .05 from baseline) during sodium citrate infusion. Serum 1,25D
      levels and plasma FGF23 values remained unchanged during both infusions in both
      groups. CONCLUSIONS: Short-term changes in calcium and PTH levels do not affect
      FGF23 concentrations in either healthy volunteers or dialysis patients.

PMID- 25062463
TI  - Clinical review: Effect of vitamin D3 supplementation on improving glucose
      homeostasis and preventing diabetes: a systematic review and meta-analysis.
AB  - CONTEXT: Observational studies report consistent associations between low vitamin
      D concentration and increased glycemia and risk of type 2 diabetes, but results
      of randomized controlled trials (RCTs) are mixed. OBJECTIVE: The objective of the
      study was to systematically review RCTs that report on the effects of vitamin D
      supplementation on glucose homeostasis or diabetes prevention. DATA SOURCES:
      Sources of data for the study were MEDLINE, EMBASE, SCOPUS, Cochrane Database of
      Systematic Reviews, Database of Abstracts of Reviews of Effects, Health
      Technology Assessment, and Science Citation Index from inception to June 2013.
      STUDY SELECTION: Study selection was trials that compared vitamin D3
      supplementation with placebo or a non-vitamin D supplement in adults with normal
      glucose tolerance, prediabetes, or type 2 diabetes. DATA EXTRACTION AND
      SYNTHESIS: Two reviewers collected data and assessed trial quality using the
      Cochrane Risk of Bias tool. Random-effects models were used to estimate mean
      differences (MDs) and odds ratios. The main outcomes of interest were homeostasis
      model assessment of insulin resistance, homeostasis model assessment of beta-cell
      function, hemoglobin A1c levels, fasting blood glucose, incident diabetes, and
      adverse events. DATA SYNTHESIS: Thirty-five trials (43 407 patients) with
      variable risk of bias were included. Vitamin D had no significant effects on
      insulin resistance [homeostasis model assessment of insulin resistance: MD -0.04;
      95% confidence interval (CI) -0.30 to 0.22, I-squared statistic (I(2)) = 45%],
      insulin secretion (homeostasis model of beta-cell function: MD 1.64; 95% CI 
      25.94 to 29.22, I(2) = 40%), or hemoglobin A1c (MD -0.05%; 95% CI -0.12 to 0.03,
      I(2) = 55%) compared with controls. Four RCTs reported on the progression to new
      diabetes and found no effect of vitamin D (odds ratio 1.02; 95% CI 0.94 to 1.10,
      I(2) = 0%). Adverse events were rare, and there was no evidence of publication
      bias. CONCLUSIONS: Evidence from available trials shows no effect of vitamin D3
      supplementation on glucose homeostasis or diabetes prevention. Definitive
      conclusions may be limited in the context of the moderate degree of
      heterogeneity, variable risk of bias, and short-term follow-up duration of the
      available evidence to date.

PMID- 25062464
TI  - Impact of duration of critical illness on the adrenal glands of human intensive
      care patients.
AB  - CONTEXT: Adrenal insufficiency is considered to be prevalent during critical
      illness, although the pathophysiology, diagnostic criteria, and optimal
      therapeutic strategy remain controversial. During critical illness, reduced
      cortisol breakdown contributes substantially to elevated plasma cortisol and low
      plasma ACTH concentrations. OBJECTIVE: Because ACTH has a trophic impact on the
      adrenal cortex, we hypothesized that with a longer duration of critical illness,
      subnormal ACTH adrenocortical stimulation predisposes to adrenal insufficiency.
      DESIGN, SETTING AND PARTICIPANTS: Adrenal glands were harvested 24 hours or
      sooner after death from 13 long intensive care unit (ICU)-stay patients, 27 short
      ICU-stay patients, and 13 controls. Prior glucocorticoid treatment was excluded.
      MAIN OUTCOME AND MEASURE(S): Microscopic adrenocortical zonational structure was
      evaluated by hematoxylin and eosin staining. The amount of adrenal cholesterol
      esters was determined by Oil-Red-O staining, and mRNA expression of ACTH
      regulated steroidogenic enzymes was quantified. RESULTS: The adrenocortical
      zonational structure was disturbed in patients as compared with controls (P <
      .0001), with indistinguishable adrenocortical zones present only in long ICU-stay
      patients (P = .003 vs. controls). Adrenal glands from long ICU-stay patients, but
      not those of short ICU-stay patients, contained 21% less protein (P = .03) and 9%
      more fluid (P = .01) than those from controls, whereas they tended to weigh less
      for comparable adrenal surface area. There was 78% less Oil-Red-O staining in
      long ICU-stay patients than in controls and in short-stay patients (P = .03), the
      latter similar to controls (P = .31). The mRNA expression of melanocortin 2
      receptor, scavenger-receptor class B, member 1, 3-hydroxy-3-methylglutaryl-CoA
      reductase, steroidogenic acute regulatory protein, and cytochrome P450
      cholesterol side-chain cleavage enzyme was at least 58% lower in long ICU-stay
      patients than in controls (all P <= .03) and of melanocortin 2 receptor,
      scavenger-receptor class B, member 1, steroidogenic acute regulatory protein, and
      cytochrome P450 cholesterol side-chain cleavage enzyme at least 53% lower than in
      short ICU-stay patients (all P <= .04), whereas gene expression in short ICU-stay
      patients was similar to controls. CONCLUSION AND RELEVANCE: Lipid depletion and
      reduced ACTH-regulated gene expression in prolonged critical illness suggest that
      sustained lack of ACTH may contribute to the risk of adrenal insufficiency in
      long-stay ICU patients.

PMID- 25062465
TI  - Micellization behavior of morpholinium-based amide-functionalized ionic liquids
      in aqueous media.
AB  - Morpholinium-based amide-functionalized ionic liquids (ILs) [C(n)AMorph][Br],
      where n = 8, 12, and 16, have been synthesized and characterized for their
      micellization behavior in aqueous medium using a variety of state of the art
      techniques. The adsorption and micellization behavior of [CnAMorph][Br] ILs at
      the air-solution interface and in the bulk, respectively, has been found to be
      much better compared to that observed for nonfunctionalized homologous ILs and
      conventional cationic surfactants, as shown by the comparatively higher
      adsorption efficiency, lower surface tension at the critical micelle
      concentraiton (gamma(cmc)), and much lower critical micelle concentration (cmc)
      for [C(n)AMorph][Br] ILs. Conductivity measurements have been performed to obtain
      the cmc, degree of counterion binding (beta), and standard free energy of
      micellization (DeltaG(m) degrees ). Isothermal titration calorimetry has provided
      information specifically about the thermodynamics of micellization, whereas
      steady-state fluorescence has been used to obtain the cmc, micropolarity of the
      cybotactic region, and aggregation number (N(agg)) of the micelles. Both dynamic
      light scattering and atomic force microscopy have provided insights into the size
      and shape of the micelles. 2D (1)H-(1)H nuclear Overhauser effect spectroscopy
      experiments have provided insights into the structure of the micelle, where
      [C16AMorph][Br] has shown distinct micellization behavior as compared to
      [C8AMorph][Br] and [C12AMorph][Br] in corroboration with observations made from
      other techniques.

PMID- 25062466
TI  - Who avoids going to the doctor and why? Audience segmentation analysis for
      application of message development.
AB  - This exploratory study examines the prevalent and detrimental health care
      phenomenon of patient delay in order to inform formative research leading to the
      design of communication strategies. Delayed medical care diminishes optimal
      treatment choices, negatively impacts prognosis, and increases medical costs.
      Various communication strategies have been employed to combat patient delay, with
      limited success. This study fills a gap in research informing those interventions
      by focusing on the portion of patient delay occurring after symptoms have been
      assessed as a sign of illness and the need for medical care has been determined.
      We used CHAID segmentation analysis to produce homogeneous segments from the
      sample according to the propensity to avoid medical care. CHAID is a criterion
      based predictive cluster analysis technique. CHAID examines a variety of
      characteristics to find the one most strongly associated with avoiding doctor
      visits through a chi-squared test and assessment of statistical significance. The
      characteristics identified then define the segments. Fourteen segments were
      produced. Age was the first delineating characteristic, with younger age groups
      comprising a greater proportion of avoiders. Other segments containing a
      comparatively larger percent of avoiders were characterized by lower income,
      lower education, being uninsured, and being male. Each segment was assessed for
      psychographic properties associated with avoiding care, reasons for avoiding
      care, and trust in health information sources. While the segments display
      distinct profiles, having had positive provider experiences, having high health
      self-efficacy, and having an internal rather than external or chance locus of
      control were associated with low avoidance among several segments. Several
      segments were either more or less likely to cite time or money as the reason for
      avoiding care. And several older aged segments were less likely than the
      remaining sample to trust the government as a source for health information.
      Implications for future research are discussed. 

PMID- 25062467
TI  - From {Au(I)...Au(I)}-coupled cages to the cage-built 2-D {Au(I)...Au(I)} arrays:
      Au(I)...Au(I) bonding interaction driven self-assembly and their Ag(I) sensing
      and photo-switchable behavior.
AB  - Metal-metal bonding interactions have been used to generate a number of unique
      supramolecular assemblies with fascinating functions. We presented here a new
      class of gold(I)-containing metallosupramolecular cages and cage-built two
      dimensional (2-D) arrays of {Au8L2}n (n = 1 or infinity, L = tetrakis
      dithiocarbamato-calix[4]arene, TDCC), 1-3, which are constructed from the self
      assembly of deep-cavitand calix[4]arene-based supramolecular cages consisting of
      octanuclear Au(I) motifs. Synchrotron radiation X-ray diffraction structural
      analyses of 1-3 revealed their quadruple-stranded helicate dimeric cage structure
      and the presence of 2-D arrays of cages linked together by inter- and
      intramolecular Au(I)...Au(I) interactions. Electronic absorption and emission
      studies of complexes 1-3 indicated the occurrence of a programmable self-assembly
      process in a concentration-dependent stepwise manner with the links built via
      aurophilic interactions. These novel gold(I) supramolecular cages exhibited green
      phosphorescence and have been shown to serve as highly selective proof-of-concept
      luminescent sensors toward Ag(I) cation among various competitive transition
      metal ions. 

PMID- 25062468
TI  - Design and synthesis of new benzimidazole-carbazole conjugates for the
      stabilization of human telomeric DNA, telomerase inhibition, and their selective
      action on cancer cells.
AB  - Cell-permeable small molecules that enhance the stability of the G-quadruplex
      (G4) DNA structures are currently among the most intensively pursued ligands for
      inhibition of the telomerase activity. Herein we report the design and syntheses
      of four novel benzimidazole-carbazole conjugates and demonstrate their high
      binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G
      quadruplex DNA protection. Additional evidence from Telomeric Repeat
      Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase
      inhibition activity by the ligands. Two of the ligands showed IC50 values in the
      sub-micromolar range in the TRAP-LIG assay, which are the best among the
      benzimidazole derivatives reported so far. The ligands also exhibited cancer cell
      selective nuclear internalization, nuclear condensation, fragmentation, and
      eventually antiproliferative activity in long-term cell viability assays. Annexin
      V-FITC/PI staining assays confirm that the cell death induced by the ligands
      follows an apoptotic pathway. An insight into the mode of ligand binding was
      obtained from the molecular dynamics simulations. 

PMID- 25062469
TI  - Vocal learning in elephants: neural bases and adaptive context.
AB  - In the last decade clear evidence has accumulated that elephants are capable of
      vocal production learning. Examples of vocal imitation are documented in African
      (Loxodonta africana) and Asian (Elephas maximus) elephants, but little is known
      about the function of vocal learning within the natural communication systems of
      either species. We are also just starting to identify the neural basis of
      elephant vocalizations. The African elephant diencephalon and brainstem possess
      specializations related to aspects of neural information processing in the motor
      system (affecting the timing and learning of trunk movements) and the auditory
      and vocalization system. Comparative interdisciplinary (from behavioral to
      neuroanatomical) studies are strongly warranted to increase our understanding of
      both vocal learning and vocal behavior in elephants. 

PMID- 25062470
TI  - Iterated learning and the evolution of language.
AB  - Iterated learning describes the process whereby an individual learns their
      behaviour by exposure to another individual's behaviour, who themselves learnt it
      in the same way. It can be seen as a key mechanism of cultural evolution. We
      review various methods for understanding how behaviour is shaped by the iterated
      learning process: computational agent-based simulations; mathematical modelling;
      and laboratory experiments in humans and non-human animals. We show how this
      framework has been used to explain the origins of structure in language, and
      argue that cultural evolution must be considered alongside biological evolution
      in explanations of language origins. 

PMID- 25062471
TI  - The role of ultrasonic vocalizations in mouse communication.
AB  - Human speech and language underlie many aspects of social behavior and thus
      understanding their ultimate evolutionary function and proximate genetic and
      neural mechanisms is a fundamental goal in neuroscience. Mouse ultrasonic
      vocalizations have recently received enormous attention as possible models for
      human speech. This attention has raised the question of whether these
      vocalizations are learned and what roles they play in communication. In this
      review, we first discuss recent evidence that ultrasonic vocalizations are not
      learned. We then review current evidence addressing how adult vocalizations may
      communicate courtship, territorial and/or other information. While there is
      growing evidence that these signals play key roles in communication, many
      important questions remain unanswered. 

PMID- 25062472
TI  - Fish bioacoustics.
AB  - Bony fishes have evolved a diversity of sound generating mechanisms and produce a
      variety of sounds. By contrast to sound generating mechanisms, which are lacking
      in several taxa, all fish species possess inner ears for sound detection. Fishes
      may also have various accessory structures such as auditory ossicles to improve
      hearing. The distribution of sound generating mechanisms and accessory hearing
      structures among fishes indicates that acoustic communication was not the driving
      force in their evolution. It is proposed here that different constraints
      influenced hearing and sound production during fish evolution, namely certain
      life history traits (territoriality, mate attraction) in the case of sound
      generating mechanisms, and adaptation to different soundscapes (ambient noise
      conditions) in accessory hearing structures (Ecoacoustical constraints
      hypothesis). 

PMID- 25062474
TI  - Nodes and networks in the neural architecture for language: Broca's region and
      beyond.
AB  - Current views on the neurobiological underpinnings of language are discussed that
      deviate in a number of ways from the classical Wernicke-Lichtheim-Geschwind
      model. More areas than Broca's and Wernicke's region are involved in language.
      Moreover, a division along the axis of language production and language
      comprehension does not seem to be warranted. Instead, for central aspects of
      language processing neural infrastructure is shared between production and
      comprehension. Three different accounts of the role of Broca's area in language
      are discussed. Arguments are presented in favor of a dynamic network view, in
      which the functionality of a region is co-determined by the network of regions in
      which it is embedded at particular moments in time. Finally, core regions of
      language processing need to interact with other networks (e.g. the attentional
      networks and the ToM network) to establish full functionality of language and
      communication. 

PMID- 25062473
TI  - The neurobiology of primate vocal communication.
AB  - Recent investigations of non-human primate communication revealed vocal behaviors
      far more complex than previously appreciated. Understanding the neural basis of
      these communicative behaviors is important as it has the potential to reveal the
      basic underpinnings of the still more complex human speech. The latest work
      revealed vocalization-sensitive regions both within and beyond the traditional
      boundaries of the central auditory system. The importance and mechanisms of multi
      sensory face-voice integration in vocal communication are also increasingly
      apparent. Finally, studies on the mechanisms of vocal production demonstrated
      auditory-motor interactions that may allow for self-monitoring and vocal control.
      We review the current work in these areas of primate communication research. 

PMID- 25062475
TI  - Antrodia camphorata induces G(1) cell-cycle arrest in human premyelocytic
      leukemia (HL-60) cells and suppresses tumor growth in athymic nude mice.
AB  - Antrodia camphorata is a well-known medicinal mushroom in Taiwan. The broth from
      a fermented culture of Antrodia camphorata (AC) has been shown to induce
      apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present
      study, we examined the effects of AC on cell cycle arrest in vitro in HL-60 cells
      and on tumor regression in vivo using an athymic nude mouse model. We found that
      AC (20-80 MUg mL(-1)) treatment significantly induced G1 cell-cycle arrest in HL
      60 cells by reducing the levels of cyclin D1, CDK4, cyclin E, CDK2, cyclin A, and
      phosphorylation of retinoblastoma protein (p-Rb). Moreover, AC treatment led to
      significantly increased protein expression levels of CDK inhibitors, including
      p21(WAF1) and p15(NIK4B). Additionally, AC treatment markedly induced
      intracellular ROS generation and mitochondrial dysfunction in HL-60 cells.
      Furthermore, the in vivo study results revealed that AC treatment was effective
      in terms of delaying the tumor incidence in nude mice that had been inoculated
      with HL-60 cells as well as in reducing the tumor burden. Histological analysis
      confirmed that AC treatment significantly modulated the xenografted tumor
      progression as demonstrated by a reduction in mitotic cells. Our data strongly
      suggest that Antrodia camphorata could be an anti-cancer agent for human
      leukemia. 

PMID- 25062476
TI  - A theory of states and traits--revised.
AB  - We present a revision of latent state-trait (LST-R) theory with new definitions
      of states and traits. This theory applies whenever we study the consistency of
      behavior, its variability, and its change over time. States and traits are
      defined in terms of probability theory. This allows for a seamless transition
      from theory to statistical modeling of empirical data. LST-R theory not only
      gives insights into the nature of latent variables but it also takes into account
      four fundamental facts: Observations are fallible, they never happen in a
      situational vacuum, they are always made using a specific method of observations,
      and there is no person without a past. Although the first fact necessitates
      considering measurement error, the second fact requires allowances for
      situational fluctuations. The third fact implies that, in the first place, states
      and traits are method specific. Furthermore, compared to the previous version of
      LST theory (see, e.g., Steyer et al. 1992 , 1999 ), our revision is based on the
      notion of a person-at-time-t. The new definitions in LST-R theory have far
      reaching implications that not only concern the properties of states, traits, and
      the associated concepts of measurement errors and state residuals, but also are
      related to the analysis of states and traits in longitudinal observational and
      intervention studies. 

PMID- 25062477
TI  - Chiral separation and determination of amino acids in real samples by LE-MEKC
      using Cu(II)-L-proline as chiral selector.
AB  - This work reports that Cu(II) complexes with l-proline were used as chiral
      additives for the enantioseparations and determination of three underivatized
      amino acids by ligand-exchange micellar electrokinetic chromatography (LE-MEKC).
      Sodium dodecylsulfate (SDS) was shown to be necessary for simultaneous separation
      of the enantiomeric amino acids. Separation parameters such as SDS
      concentrations, the Cu(II)-l-proline ratio, the concentration of the copper(II)
      complex at a specific Cu(II)-l-proline ratio, pH and separation voltage were
      investigated for the enantioseparation in order to achieve the maximum possible
      resolution. A good separation was achieved in the BGE composing of 10mM ammonium
      acetate, 10mM Cu(II) and 20mM l-proline and 30 mM SDS at pH 5.0, and an applied
      voltage of 15 kV performed. Under above-mentioned optimum conditions, linearity
      was achieved within concentration ranges of up to two orders of magnitudes for
      the investigated amino acids with the correlation coefficients ranging from
      0.9917 to 0.9984. The proposed method has been successfully applied to the
      determination of amino acid enantiomers in human urine, compound amino acids
      injection, and amino acid oral liquid.

PMID- 25062478
TI  - The size-reactivity continuum of major bioelements in the ocean.
AB  - Most of the carbon fixed in primary production is rapidly cycled and
      remineralized, leaving behind various forms of organic carbon that contribute to
      a vast reservoir of nonliving organic matter in seawater. Most of this carbon
      resides in dissolved molecules of varying bioavailability and reactivity, and
      aspects of the cycling of this carbon remain an enigma. The size-reactivity
      continuum model provides a conceptual framework for understanding the mechanisms
      governing the formation and mineralization of this carbon. In the seawater
      bioassay experiments that served as the original basis for this model,
      investigators observed that larger size classes of organic matter were more
      bioavailable and more rapidly remineralized by microbes than were smaller size
      classes. Studies of the chemical composition and radiocarbon content of marine
      organic matter have further indicated that the complexity and age of organic
      matter increase with decreasing molecular size. Biodegradation processes appear
      to shape the size distribution of organic matter and the nature of the small
      dissolved molecules that persist in the ocean.

PMID- 25062479
TI  - Diversity and potential application of endophytic bacteria in ginger.
AB  - Here, 248 endophytic bacterial strains were isolated to assess the distribution
      and population diversity of endophytic bacteria in ginger plants. A total of 10.4
      x 10(4) to 20.2 x 10(4) CFU/g fresh weight endophytic bacteria of different
      growth stages were isolated. Maximum bacterium numbers were obtained at the
      seedling stage. A total of 107 functional strains were screened, including 17
      antibacterial strains and 90 indole acetic acid-producing strains. Based on 16S
      rDNA sequence restriction fragment length polymorphism and 16S rDNA sequences,
      these 107 strains were mapped and grouped into 16 genera. Bacillus and
      Pseudomonas were the dominant genera; however, the bacteria belonged to a
      tremendous range of genera, with the highest species richness being observed at
      the seedling stage. Sixteen strains exhibited antimicrobial activity against
      Pythium myriotylum Drechsler, while 7 strains exhibited antimicrobial activity
      against Phyllosticta zingiberi Hori. Bacillus was the dominant antibacterial
      strain. Pseudomonas fluorescens, B. megaterium, and Enterobacter ludwigii
      produced remarkably high levels of IAA. Only a few endophytic bacterial strains
      were inhibited in fresh ginger juice. Most of these strains were present during
      seedling stage, including Roseateles depolymerans, Chryseobacterium taiwanense,
      E. ludwigii, Agrobacterium larrymoorei, P. fluorescens, and Bacillus
      amyloliquefaciens. This study indicates that the community of endophytic bacteria
      in ginger changes with the synthesis of antibacterial substances. 

PMID- 25062480
TI  - Evolution of CD4+CD25(hi) T cell subsets in Aspergillus-infected liver
      transplantation recipients reduces the incidence of transplantation rejection via
      upregulating the production of anti-inflammatory cytokines.
AB  - Infection is the leading risk factor of liver transplantation-related death.
      Aspergillosis is a life-threatening complication in immune-compromised patients,
      and is the cause of approximately 2/3 of deaths in liver transplant recipients.
      In our previous studies, we found a regulatory T cell (Treg) population that
      showed significantly increased immune tolerance in Aspergillus-infected liver
      transplant recipients. Furthermore, interleukin (IL)-17 production was also
      increased, and an IL-17-producing Treg cell subset was identified in these
      patients. Functional studies of the role of these IL-17-producing Treg cells in
      the induction of immune tolerance are needed to help reduce the death rate of
      liver transplantation recipients. This study included 75 liver transplant
      recipients with and without histologically confirmed aspergillosis after liver
      transplantation. The percentage of T cell population subsets producing cytokines
      was detected by fluorescence-activated cell sorting and enzyme-linked
      immunosorbent assay in peripheral blood. Complements in blood serum were also
      examined. The risk of acute rejection was lower in Aspergillus-infected liver
      transplant recipients compared to the non-Aspergillus-infected group; the
      CD4(+)CD25(hi) T cell population in peripheral blood was higher and the
      CD4(+)CD45RA-CD45RO(+) T cell population was lower. There was no significant
      difference between the CD4(+)CD25(lo)CD45RA(+) and CD4(+)CD25(lo)CD45RA- T cell
      populations. Moreover, IL-6 decreased and IL-4 increased in the blood serum of
      Aspergillus-infected liver transplant recipients. Together, these results
      indicate that the incidence of graft rejection in liver transplantation
      recipients with Aspergillus infections was lower than that of the non-infected
      group, and suggests a mechanism for this effect. 

PMID- 25062481
TI  - Mitochondrial gene expression in the liver and muscle of high and low feed
      efficiency Japanese quail layers subjected to different environmental
      temperatures.
AB  - We evaluated the adenine nucleotide translocator (ANT) and cytochrome oxidase
      subunit III (COX III) mRNA expressions in the muscle and liver of Japanese quails
      presenting high and low feed efficiency (FE), and subjected them to three
      different environmental temperatures: comfort, heat stress (38 degrees C), and
      cold stress (10 degrees C). ANT mRNA expression was lower in the liver of heat
      stressed animals. In the muscle, higher ANT and COX III mRNA expressions were
      observed in high-FE and cold-stressed animals. In the liver, much higher
      expression of COX III mRNA was observed in cold-stressed animals. These results
      suggest a possible correlation between the genes involved in energy production by
      the mitochondria and FE phenotypes, and that environmental temperature can affect
      the ANT and COX III mRNA expressions. Japanese quails presenting different FE
      levels respond differently to environmental stimuli. 

PMID- 25062482
TI  - Cloning and sequence analysis of an actin gene in aloe.
AB  - Aloe (Aloe spp), containing abundant polysaccharides and numerous bioactive
      ingredients, has remarkable medical, ornamental, calleidic, and edible values. In
      the present study, the total RNA was extracted from aloe leaf tissue. The
      isolated high-quality RNA was further used to clone actin gene by using reverse
      transcription-polymerase chain reaction (RT-PCR). The result of sequence analysis
      for the amplified fragment revealed that the cloned actin gene was 1012 bp in
      length (GenBank accession No. KC751541.1) and contained a 924-bp coding region
      and encoded a protein consisting of 307 amino acids. Homologous alignment showed
      that it shared over 80 and 96% identity with the nucleotide and amino acid
      sequences of actin from other plants, respectively. In addition, the cloned gene
      was used for phylogenetic analyses based on the deduced amino acid sequences, and
      the results suggested that the actin gene is highly conserved in evolution. The
      findings of this study will be useful for investigating the expression patterns
      of other genes in Aloe. 

PMID- 25062483
TI  - Lipopolysaccharide and beta-1,3-glucan binding protein in the hard clam (Meretrix
      meretrix): molecular characterization and expression analysis.
AB  - Pattern recognition molecules play an important role in innate immunity by
      recognizing conserved molecular patterns that are present on the surface of
      invading microorganisms. In this study, a lipopolysaccharide and beta-1,3-glucan
      binding protein (LGBP) gene was cloned from the hard clam Meretrix meretrix
      (designated as Mm-LGBP) by the expressed sequence tags and rapid amplification of
      cDNA ends method. The cDNA was 1827 bp in length, consisting of a 71-bp 5'
      terminal untranslated region, a 62-bp 3'UTR, and a 1734-bp open reading frame
      encoding a 577-amino acid polypeptide with an estimated molecular mass of 60.7
      kDa and a theoretical isoelectric point of 5.56. Characteristic potential
      polysaccharide binding, cell adhesion, and glucanase motifs were identified in
      the Mm-LGBP, indicating that Mm-LGBP should be a new member of the LGBP family.
      Quantitative real-time polymerase chain reaction was developed to detect the mRNA
      expression level of Mm-LGBP in 6 different tissues. Higher-level mRNA expression
      of Mm-LGBP was detected in the gill and digestive gland tissues. The upregulation
      of Mm-LGBP mRNA after Vibrio anguillarum challenge showed that Mm-LGBP play a
      pivotal role in antibacterial immunity. 

PMID- 25062484
TI  - Isolation and characterization of genetic variability in bacteria with beta
      hemolytic and antifungal activity isolated from the rhizosphere of Medicago
      truncatula plants.
AB  - In the present study, we analyzed the frequency of hemolytic and antifungal
      activities in bacterial isolates from the rhizosphere of Medicago truncatula
      plants. Of the 2000 bacterial colonies, 96 showed beta-hemolytic activities
      (frequency, 4.8 x 10(-2)). Hemolytic isolates were analyzed for their genetic
      diversity by using random amplification of polymorphic DNA, yielding 88
      haplotypes. The similarity coefficient of Nei and Li showed a polymorphic
      diversity ranging from 0.3 to 1. Additionally, 8 of the hemolytic isolates showed
      antifungal activity toward plant pathogens, Diaporthe phaseolorum, Colletotrichum
      acutatum, Rhizoctonia solani, and Fusarium oxysporum. The 16S ribosomal
      sequencing analysis showed that antagonistic bacterial isolates corresponded to
      Bacillus subtilis (UM15, UM33, UM42, UM49, UM52, and UM91), Bacillus pumilus
      (UM24), and Bacillus licheniformis (UM88). The present results revealed a higher
      genetic diversity among hemolytic isolates compared to that of isolates with
      antifungal action. 

PMID- 25062485
TI  - Hepatocyte growth factor upregulates nexilin gene expression in cardiomyocytes
      via JNK pathway.
AB  - Hepatocyte growth factor (HGF) is a protective factor in myocardial injury, but
      its mechanisms of action have not yet been fully elucidated. Nexilin, which
      locates specifically to the Z-disc, is a novel Z-disc protein that enables the Z
      discs to persistently withstand the extreme mechanical forces generated during
      muscle contraction. Therefore, we investigated the role of HGF in modulating
      nexilin expression in hypoxia-reoxygenation (H/R)-treated cardiomyocytes. We
      cultured neonatal cardiomyocytes and treated them with HGF. The mRNA and protein
      levels of nexilin were determined by RT-PCR and Western blotting. H/R treatment
      decreased nexilin mRNA expression and nexilin protein levels in cardiomyocytes.
      Furthermore, treatment with HGF upregulated nexilin expression and the JNK
      inhibitor SP600125 partly inhibited HGF-induced nexilin upregulation. In
      conclusion, our results suggest that ischemia-reperfusion injury may downregulate
      nexilin expression in cardiomyocytes, and HGF may exert its protective role
      during myocardial ischemic injury through upregulation of nexilin expression in
      cardiomyocytes. 

PMID- 25062486
TI  - Genetic analysis of the major gene plus polygene model in soybean resistance to
      Leguminivora glycinivorella.
AB  - In order to investigate the genetic characteristics of soybean Leguminivora
      glycinivorella resistance and to improve soybean resistance insectivorous
      breeding efficiency by applying the multi-generation joint analysis method of the
      major gene plus polygene model, 5 pedigrees and generations (P1, F1, P2, F2, and
      F2:3) were used as the materials to perform the soybean L. glycinivorella
      resistance multi-generation joint analysis. The results showed that soybean
      resistance to L. glycinivorella was controlled and inherited by an additive major
      gene plus additive, dominant polygene. The major gene had a negative additive
      effect (d = -0.1633). The combination of the anti-L. glycinivorella genes showed
      negative heterosis. Because the polygene additive effects were positive, the
      polygene effects would increase the insect herbivory rate in the F1 generation.
      This hybrid combination showed an insect herbivory rate polygenic heritability of
      21.9556 and 54.3490% in the F2 and F2:3 pedigrees, which presented a high
      heritability. Therefore, it was appropriate to perform the selective breeding of
      the insect herbivory rate in the late generation. 

PMID- 25062487
TI  - Effect of codon optimization on expression levels of human cystatin C in Pichia
      pastoris.
AB  - Human cystatin C (CysC) is a cysteine proteinase inhibitor with many potential
      applications. To facilitate further studies of the functions and applications of
      CysC, we improved the heterologous expression of CysC using a basic codon
      optimization method. In this study, we cloned the high-GC content wild-type
      sequence of the CysC gene and also designed a slightly AT-biased sequence, with
      codons optimized for expression in the Pichia pastoris GS115 strain. Our results
      showed that the optimized coding sequence of human CysC increased the expression
      and secretion of the CysC protein by approximately 3- to 5-fold (90-96 mg CysC/L)
      in yeast, compared with the expression levels of the native CysC gene (17.9-18.4
      mg CysC/L). We designed, constructed, and applied an optimized version of the
      CysC gene for the Pichia expression system. Our results demonstrate that the
      optimized coding sequence provides a higher yield of secreted CysC than that
      produced using the wild-type gene. Our data also serve as a practical example
      demonstrating a rational design strategy for the heterologous expression of
      secreted proteins. 

PMID- 25062488
TI  - Influence of paeoniflorin on intracellular calcium ion concentration in the
      sphincter of Oddi of hypercholesterolemic rabbits.
AB  - This study aimed to investigate the influence of hypercholesterolemia (HC) on
      intracellular calcium ion concentration in the sphincter of Oddi (SO) of rabbits
      and the influence of paeoniflorin on intracellular calcium ion concentration in
      the hypercholesterolemic rabbit SO. Sixteen purebred New Zealand rabbits were
      randomly divided into two groups: the control group and the HC model group (8
      rabbits in each group). The control group was fed standard diet. The HC group was
      fed standard diet plus cholesterol for a total of 8 weeks to induce and establish
      the rabbit HC model. The SO segment of HC rabbits was taken and enzyme treated to
      obtain SO cells. After primary culture, immunohistochemical analysis was
      performed. Fluo-3/AM was used to load SO cells, and then intracellular calcium
      ion concentration was determined by confocal microscopy. Intracellular calcium
      ion in the SO of the HC group was higher than that of the normal group;
      intracellular calcium ion in the HC rabbit SO of the paeoniflorin group was lower
      than that of the control group, where the paeoniflorin effect was greater with
      higher concentrations. High cholesterol caused an increase in intracellular
      calcium ion concentration in the rabbit SO, and paeoniflorin can reduce
      intracellular calcium ion concentration in the HC rabbit SO in a concentration
      dependent manner. 

PMID- 25062489
TI  - Predictive role of vascular endothelial growth factor polymorphisms in the
      survival of renal cell carcinoma patients.
AB  - We conducted a study to investigate the possible role of the vascular endothelial
      growth factor (VEGF) polymorphisms -2578C/A, -1154G/A and -634C/G and clinical
      factors in renal cell carcinoma (RCC) prognosis in a cohort of 336 RCC cases. A
      total of 336 patients with RCC were recruited from PLA General Hospital between
      January 2004 and December 2005. All patients were followed up until December
      2010, and no patient was lost to follow-up. The follow-up time of this study was
      60 months. At the time of analysis, a total of 210 died during the follow-up. The
      median overall survival for patients was 29.1 months (95%CI = 17.1 to 41.3
      months), and the 5-year survival rate for the patients was 37.5%. Our study
      showed that Karnofsky performance status >=60 could delay death from RCC, with HR
      (95%CI) of 0.57 (0.39-0.84). Patients with anemia, platelet count >400 x 10(9)/L,
      neutrophilia and lymphocytes >160 g/L had increased risk of death from RCC, with
      HR (95%CI) of 1.84 (1.18-2.96), 2.01 (1.27-3.25), 1.65 (1.03-2.56) and 1.49 (0.99
      2.71), respectively. The VEGF -2578AA and -1154AA genotypes were significantly
      associated with a poor overall survival of RCC patients, with HR (95%CI) of 2.41
      (1.32-5.13) and 3.77 (1.42-15.67), respectively. In conclusion, our study
      presented the factors regarding the prognosis of RCC patients, and high platelet
      and neutrophil counts, low lymphocytes, and VEGF -2578C/A and -1154G/A
      polymorphisms were shown to be independent factors for a lower prognosis of RCC
      patients. 

PMID- 25062490
TI  - MDR1 C3435T polymorphism in Mexican patients with breast cancer.
AB  - We investigated whether the MDR1 C3435T polymorphism is associated with
      fibrocystic changes (FCC), infiltrating ductal breast cancer (IDBC), and/or
      clinical-pathological features of IDBC in Mexican patients. Samples from women
      who received surgical treatment in 2007 at the Centro Medico de Occidente
      (Mexico) were included in the analysis. Genotyping was performed by polymerase
      chain reaction-restricted fragment length polymorphisms in 64 paraffin-embedded
      breast samples with IDBC, 64 samples with FCC, and 183 peripheral blood samples
      of healthy females designated as the healthy group (HG). The frequency of the T
      allele was 41, 45, and 52% for the FCC, IDBC, and HG samples, respectively.
      Significant differences were only found between the FCC and HG samples [odds
      ratio (OR) = 0.64, 95% confidence interval (CI) = 0.43-0.96; P = 0.032]. The
      prevalence of the T/T genotype was 8, 13, and 24% for FCC, IDBC, and HG samples,
      respectively. Again, statistical differences were only found between FCC and HG
      samples for the T/T genotype (OR = 0.28, 95%CI = 0.106-0.77; P = 0.009). Although
      the T allele and the T/T genotype were less frequent in the IDBC group than in
      the HG, the differences were not significant. Furthermore, no associations were
      found between the C3435T polymorphism and clinical-pathological features of the
      IDBC group. Both the FCC and IDBC groups had a high frequency of the C allele
      relative to the HG in this sample of women from Western Mexico. 

PMID- 25062492
TI  - Efficient method of protein extraction from Theobroma cacao L. roots for two
      dimensional gel electrophoresis and mass spectrometry analyses.
AB  - Theobroma cacao is a woody and recalcitrant plant with a very high level of
      interfering compounds. Standard protocols for protein extraction were proposed
      for various types of samples, but the presence of interfering compounds in many
      samples prevented the isolation of proteins suitable for two-dimensional gel
      electrophoresis (2-DE). An efficient method to extract root proteins for 2-DE was
      established to overcome these problems. The main features of this protocol are:
      i) precipitation with trichloroacetic acid/acetone overnight to prepare the
      acetone dry powder (ADP), ii) several additional steps of sonication in the ADP
      preparation and extractions with dense sodium dodecyl sulfate and phenol, and
      iii) adding two stages of phenol extractions. Proteins were extracted from roots
      using this new protocol (Method B) and a protocol described in the literature for
      T. cacao leaves and meristems (Method A). Using these methods, we obtained a
      protein yield of about 0.7 and 2.5 mg per 1.0 g lyophilized root, and a total of
      60 and 400 spots could be separated, respectively. Through Method B, it was
      possible to isolate high-quality protein and a high yield of roots from T. cacao
      for high-quality 2-DE gels. To demonstrate the quality of the extracted proteins
      from roots of T. cacao using Method B, several protein spots were cut from the 2
      DE gels, analyzed by tandem mass spectrometry, and identified. Method B was
      further tested on Citrus roots, with a protein yield of about 2.7 mg per 1.0 g
      lyophilized root and 800 detected spots. 

PMID- 25062491
TI  - Expression analysis of self-incompatibility-associated genes in non-heading
      Chinese cabbage.
AB  - In Brassicaceae, a self-incompatibility (SI) system mediates pollen-pistil
      interactions. Self-pollen could be recognized and rejected by incompatible
      pistils. Several components involved in the SI response have been determined,
      including S-locus receptor kinase (SRK), S-locus cysteine-rich protein/S-locus
      protein 11, and arm repeat-containing protein 1 (ARC1). However, the components
      involved in the SI system of Brassicaceae are not fully understood. Here, we
      detected expression patterns of 24 SI-related genes in non-heading Chinese
      cabbage (Brassica campestris ssp chinensis Makino) after compatible and
      incompatible pollination, and potential interaction relationships of these genes
      were predicted. SRK and ARC1 transcripts increased initially 0.25 h after
      incompatible pollination, while kinase-associated protein phosphatase had an
      expression pattern that was opposite that of SRK transcripts during self
      pollination. Plant U-box 8 was not required in the SI response of non-heading
      Chinese cabbage. Our results showed that the SI signal of non-heading Chinese
      cabbage could occur within 0.25 h after self-pollination. The hypothetical
      interaction relationships indicated that plastid-lipid-associated protein and
      malate dehydrogenase could be negatively regulated by chaperonin 10, glutathione
      transferase, cytidylate kinase/uridylate kinase, and methionine synthase by
      indirect interactions. Our findings could be helpful to better understand
      potential roles of these components in the SI system of non-heading Chinese
      cabbage. 

PMID- 25062493
TI  - Acetic acid promoted metal-free aerobic carbon-carbon bond forming reactions at
      alpha-position of tertiary amines.
AB  - The oxidative functionalization of the benzylic C-H bonds in
      tetrahydroisoquinolines and tetrahydro-beta-carboline derivatives was
      investigated. C-C bond forming reactions proceeded with a range of nucleophiles
      (nitroalkane, enol silyl ether, indole, allylstannane, and tetrabutylammonium
      cyanide) under metal-free conditions and an oxygen atmosphere. Acetic acid caused
      a significant acceleration effect. 

PMID- 25062494
TI  - A large community outbreak of gastroenteritis associated with consumption of
      drinking water contaminated by river water, Belgium, 2010.
AB  - SUMMARY On 6 December 2010 a fire in Hemiksem, Belgium, was extinguished by the
      fire brigade with both river water and tap water. Local physicians were asked to
      report all cases of gastroenteritis. We conducted a retrospective cohort study
      among 1000 randomly selected households. We performed a statistical and
      geospatial analysis. Human stool samples, tap water and river water were tested
      for pathogens. Of the 1185 persons living in the 528 responding households, 222
      (18.7%) reported symptoms of gastroenteritis during the time period 6-13
      December. Drinking tap water was significantly associated with an increased risk
      for gastroenteritis (relative risk 3.67, 95% confidence interval 2.86-4.70) as
      was place of residence. Campylobacter sp. (2/56), norovirus GI and GII (11/56),
      rotavirus (1/56) and Giardia lamblia (3/56) were detected in stool samples. Tap
      water samples tested positive for faecal indicator bacteria and protozoa. The
      results support the hypothesis that a point-source contamination of the tap water
      with river water was the cause of the multi-pathogen waterborne outbreak. 

PMID- 25062495
TI  - Borrelia crocidurae infection in acutely febrile patients, Senegal.
AB  - As malaria cases in Africa decline, other causes of acute febrile illness are
      being explored. To determine incidence of Borrelia crocidurae infection during
      June 2010-October 2011, we collected 1,566 blood specimens from febrile patients
      in Senegal. Incidence was high (7.3%). New treatment strategies, possibly
      doxycycline, might be indicated for febrile patients. 

PMID- 25062496
TI  - Position paper for the organization of extracorporeal membrane oxygenation
      programs for acute respiratory failure in adult patients.
AB  - The use of extracorporeal membrane oxygenation (ECMO) for severe acute
      respiratory failure (ARF) in adults is growing rapidly given recent advances in
      technology, even though there is controversy regarding the evidence justifying
      its use. Because ECMO is a complex, high-risk, and costly modality, at present it
      should be conducted in centers with sufficient experience, volume, and expertise
      to ensure it is used safely. This position paper represents the consensus opinion
      of an international group of physicians and associated health-care workers who
      have expertise in therapeutic modalities used in the treatment of patients with
      severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians,
      ECMO center directors and coordinators, hospital directors, health-care
      organizations, and regional, national, and international policy makers a
      description of the optimal approach to organizing ECMO programs for ARF in adult
      patients. Importantly, this will help ensure that ECMO is delivered safely and
      proficiently, such that future observational and randomized clinical trials
      assessing this technique may be performed by experienced centers under
      homogeneous and optimal conditions. Given the need for further evidence, we
      encourage restraint in the widespread use of ECMO until we have a better
      appreciation for both the potential clinical applications and the optimal
      techniques for performing ECMO. 

PMID- 25062497
TI  - [Treatment of cognitive impairments in oncology: a review of longitudinal
      controlled studies].
AB  - Various studies highlight cognitive impairments in cancer patients. This paper
      proposes a review of longitudinal controlled studies evaluating the efficacy of
      interventions aiming to reduce these cognitive impairments. Longitudinal
      controlled studies evaluating the efficacy of interventions aiming to reduce
      cognitive impairments in adult cancer patients and published between 1993 and
      2013 were identified, with the exception of studies that implied patients
      suffering from CNS tumor or metastasis. Pharmacological interventions (n = 11)
      suggested the positive impact of modafinil on memory and executive functions. Non
      pharmacological interventions (n = 10) suggested the positive impact of cognitive
      revalidation and stimulation programs, psycho-education and meditation on several
      memory, attentional and executive objective as well as subjective functions. Non
      pharmacological interventions show more significant cognitive benefits than
      pharmacological interventions. Some longitudinal controlled studies support the
      usefulness of interventions aiming to reduce cognitive impairments in cancer
      patients. Further studies should evaluate the effectiveness of programs combining
      technics aiming to reduce cognitive impairments and psychotherapeutic technics
      aiming to support patients' coping with illness.

PMID- 25062498
TI  - Anti-asialo-GM1 and GD1a variant of Miller Fisher variant of Guillain-Barre
      Syndrome.
AB  - We present a woman with acute onset of bilateral ophthalmoparesis and ataxia
      occurring 4 weeks after gastroenteritis. Serum antibody titers against asialo-GM1
      and GD1a, typically associated with inflammatory axonal neuropathies, were
      elevated but titers against anti-GQ1b, the most commonly found antibody found in
      the Miller Fisher variant of Guillain-Barre syndrome were not. No other etiology
      for ophthalmoparesis was found despite extensive patient evaluation. Intravenous
      immunoglobulin was administered, and the patient gradually improved over
      subsequent months. This case is unique for its antiganglioside antibody profile
      associated with Miller Fisher syndrome.

PMID- 25062499
TI  - Redox control of group 4 metal ring-opening polymerization activity toward L
      lactide and epsilon-caprolactone.
AB  - The activity of several group 4 metal alkoxide complexes supported by ferrocene
      based ligands was controlled using redox reagents during the ring-opening
      polymerization of l-lactide and epsilon-caprolactone. Switching in situ between
      the oxidized and reduced forms of a metal complex resulted in a change in the
      corresponding rate of polymerization. Opposite behavior was observed for each
      monomer used. One-pot copolymerization of the two monomers to give block
      copolymers was also achieved. 

PMID- 25062501
TI  - Hetero-Diels-Alder reaction of phosphorylated nitroso alkenes with enol ethers on
      water: a clean approach toward 1,2-oxazine derivatives.
AB  - A concise and eco-friendly synthesis of highly functionalized 1,2-oxazines from
      phosphinyl- and phosphonyl-nitroso alkenes has been developed. The key step of
      this process, which involves a two-step sequence of reactions on-water, is a
      regioselective hetero-Diels-Alder cycloaddition reaction of enol ethers to 4
      phosphinyl or 4-phosphonyl nitroso alkenes mediated by water itself. The process
      has also been performed under solvent-free conditions and in organic solvents for
      comparison. 

PMID- 25062500
TI  - HDAC inhibitor-mediated beta-cell protection against cytokine-induced toxicity is
      STAT1 Tyr701 phosphorylation independent.
AB  - Histone deacetylase (HDAC) inhibition protects pancreatic beta-cells against
      apoptosis induced by the combination of the proinflammatory cytokines interleukin
      (IL)-1beta and interferon (IFN)-gamma. Decreased expression of cell damage
      related genes is observed on the transcriptional level upon HDAC inhibition using
      either IL-1beta or IFN-gamma alone. Whereas HDAC inhibition has been shown to
      regulate NFkappaB-activity, related primarily to IL-1beta signaling, it is
      unknown whether the inhibition of HDACs affect IFN-gamma signaling in beta-cells.
      Further, in non-beta-cells, there is a dispute whether HDAC inhibition regulates
      IFN-gamma signaling at the level of STAT1 Tyr701 phosphorylation. Using different
      small molecule HDAC inhibitors with varying class selectivity, INS-1E wild type
      and stable HDAC1-3 knockdown pancreatic INS-1 cell lines, we show that IFN-gamma
      induced Cxcl9 and iNos expression as well as Cxcl9 and GAS reporter activity were
      decreased by HDAC inhibition in a STAT1 Tyr701 phosphorylation-independent
      fashion. In fact, knockdown of HDAC1 increased IFN-gamma-induced STAT1
      phosphorylation. 

PMID- 25062502
TI  - Biodegradable poly(vinyl alcohol) foams supported by cellulose nanofibrils:
      processing, structure, and properties.
AB  - In order to capture savings in energy and ambitious environmental targets,
      biodegradable composite foams of poly(vinyl alcohol) (PVA) supported by cellulose
      nanofibrils (CNF) were prepared through unidirectional freeze-drying technology.
      Effects of the content of CNF, the solid content of the precursor suspension, and
      the quenching temperature on the microstructure and properties of the composite
      foams were investigated by scanning electron microscopy (SEM), compressive
      testing, X-ray diffraction (XRD) analysis, water uptake, and biodegradation
      tests. Results show that the incorporation of CNF preferably at a weight ratio of
      30 wt % greatly enhanced the mechanical strength and modulus, energy absorption,
      water resistance, and dimensional stability of the composite foams because of the
      rigid and semicrystalline nature of CNF as well as regular and compact pore
      structures. Furthermore, the biodegradation tests performed in a simulated
      aerobic compost environment suggested that the involvement of CNF significantly
      accelerated the pace of biodegradation of the composite foams. Hence, we provided
      some meaningful information on the biomimetic cellular composite foams with
      controllable morphs and properties by varying the freeze-drying process and
      composition. 

PMID- 25062503
TI  - Complex regulation of dendritic transmitter release from thalamic interneurons.
AB  - Neuronal output typically involves neurotransmitter release via axonal terminals;
      however, a subpopulation of neurons can also release neurotransmitters through
      vesicle-containing presynaptic dendrites. In the thalamus, local circuit
      inhibitory interneurons are a class of cells that can release gamma-aminobutyric
      acid (GABA) via both axon terminals (termed F1 terminals) as well as presynaptic,
      vesicle-containing dendrites (termed F2 terminals). For example, in the visual
      thalamus, these F2 terminals are tightly coupled to the primary sensory afferents
      (axons of retinogeniculate neurons) that synapse onto thalamocortical relay
      neurons. The F2 terminals are primarily localized to distal dendrites of the
      interneurons, and in certain situations the excitation/output of F2 terminals can
      occur independent of somatic activity within the interneuron thereby allowing
      these F2 terminals to serve as independent input/output components giving rise to
      focal inhibition. On the other hand, somatically evoked Na+-dependent action
      potentials can backpropagate throughout the dendritic arbor of the interneuron.
      The transient depolarizations, or stronger somatically initiated events (e.g.
      activation of low threshold calcium transients) can initiate a backpropagating
      Ca(2+)-mediated potential that invades the dendritic arbor activating F2
      terminals and leading to a global form of inhibition. These distinct types of
      output (focal versus global) could play an important role in the temporal as well
      as spatial roles of inhibition that in turn impacts thalamocortical information
      processing. 

PMID- 25062504
TI  - Dynamics and plasticity of spinal locomotor circuits.
AB  - Spinal circuits generate coordinated locomotor movements. These hardwired
      circuits are supplemented with neuromodulation that provide the necessary
      flexibility for animals to move smoothly through their environment. This review
      will highlight some recent insights gained in understanding the functional
      dynamics and plasticity of the locomotor circuits. First the mechanisms governing
      the modulation of the speed of locomotion will be discussed. Second, advantages
      of the modular organization of the locomotor networks with multiple circuits
      engaged in a task-dependent manner will be examined. Finally, the neuromodulation
      and the resulting plasticity of the locomotor circuits will be summarized with an
      emphasis on endocannabinoids and nitric oxide. The intention is to extract
      general principles of organization and discuss some onto-genetic and phylogenetic
      divergences. 

PMID- 25062505
TI  - Two tales of how expectation of reward modulates behavior.
AB  - Expectation of reward modulates many types of behaviors. Here we highlight two
      lines of research on reward-modulated perceptual decision making in primates and
      social context-modulated singing in songbirds, respectively. These two seemingly
      distinct behaviors are both known to involve cortico-basal ganglia-thalamic
      circuits. The underlying computations may be conceptualized using a simple,
      common framework. We summarize and compare our current knowledge of the two
      fields to motivate new experiments for each field, with the goal of finding
      general principles for how the brain implements reward-modulated behavior. 

PMID- 25062506
TI  - Synthesis and pharmacological evaluation of 5-pyrrolidinylquinoxalines as a novel
      class of peripherally restricted kappa-opioid receptor agonists.
AB  - 5-Pyrrolidinyl substituted perhydroquinoxalines were designed as conformationally
      restricted kappa-opioid receptor agonists restricted to the periphery. The
      additional N atom of the quinoxaline system located outside the ethylenediamine
      kappa pharmacophore allows the fine-tuning of the pharmacodynamic and
      pharmacokinetic properties. The perhydroquinoxalines were synthesized
      stereoselectively using the concept of late stage diversification of the central
      building blocks 14. In addition to high kappa-opioid receptor affinity they
      demonstrate high selectivity over MU, delta, sigma1, sigma2, and NMDA receptors.
      In the [35S]GTPgammaS assay full agonism was observed. Because of their high
      polarity, the secondary amines 14a (log D7.4=0.26) and 14b (log D7.4=0.21) did
      not penetrate an artificial blood-brain barrier. 14b was able to inhibit the
      spontaneous pain reaction after rectal mustard oil application to mice (ED50=2.35
      mg/kg). This analgesic effect is attributed to activation of peripherally located
      kappa receptors, since 14b did not affect centrally mediated referred allodynia
      and hyperalgesia.

PMID- 25062507
TI  - An open-label multicenter study to assess the safety of
      dextromethorphan/quinidine in patients with pseudobulbar affect associated with a
      range of underlying neurological conditions.
AB  - BACKGROUND: Pseudobulbar affect (PBA) is associated with neurological disorders
      or injury affecting the brain, and characterized by frequent, uncontrollable
      episodes of crying and/or laughing that are exaggerated or unrelated to the
      patient's emotional state. Clinical trials establishing dextromethorphan and
      quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic
      lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q
      safety in patients with PBA secondary to any neurological condition affecting the
      brain. OBJECTIVE: To evaluate the safety and tolerability of DM/Q during long
      term administration to patients with PBA associated with multiple neurological
      conditions. METHODS: Fifty-two-week open-label study of DM/Q 30/30 mg twice
      daily. Safety measures included adverse events (AEs), laboratory tests,
      electrocardiograms (ECGs), vital signs, and physical examinations. CLINICAL TRIAL
      REGISTRATION: #NCT00056524. RESULTS: A total of 553 PBA patients with >30
      different neurological conditions enrolled; 296 (53.5%) completed. The most
      frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness
      (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and
      dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and
      consistent with previous controlled trials. Serious AEs (SAEs) were reported in
      126 patients (22.8%), including 47 deaths, mostly due to ALS progression and
      respiratory failure. No SAEs were deemed related to DM/Q treatment by
      investigators. ECG results suggested no clinically meaningful effect of DM/Q on
      myocardial repolarization. Differences in AEs across neurological disease groups
      appeared consistent with the known morbidity of the primary neurological
      conditions. Study interpretation is limited by the small size of some disease
      groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher
      than the eventually approved dose. CONCLUSIONS: DM/Q was generally well tolerated
      over this 52 week trial in patients with PBA associated with a wide range of
      neurological conditions.

PMID- 25062509
TI  - Simultaneous determination of 50 residual pesticides in Flos Chrysanthemi using
      accelerated solvent extraction and gas chromatography.
AB  - A gas chromatographic method for simultaneous determination of 50 organochlorine
      (OCP) and pyrethroid (PP) pesticides in Flos Chrysanthemi was established.
      Accelerated solvent extraction (ASE) technique was used to extract the target
      compounds, cleaned with alumina neutral-florisil column, and eluted by mixed
      solvents of ethyl acetate and hexane (15:85, v/v). Selected pesticides were
      identified using HP-5 and DB1701 capillary dual column and detected by electron
      capture detector. Quantitative analysis was performed using an external standard
      by HP-5 capillary column. Results showed that recoveries were 73.4-120.1%, and
      the relative standard deviations (RSDs) were 1.6-12.4%. The limits of detection
      of the method were 0.0021-0.0069 mg/kg, and the limits of quantity were 0.0064
      0.0210 mg/kg.

PMID- 25062508
TI  - Cytotoxic and apoptosis-inducing activity of triterpene glycosides from
      Holothuria scabra and Cucumaria frondosa against HepG2 cells.
AB  - The cytotoxic effects of thirteen triterpene glycosides from Holothuria scabra
      Jaeger and Cucumaria frondosa Gunnerus (Holothuroidea) against four human cell
      lines were detected and their cytotoxicity-structure relationships were
      established. The apoptosis-inducing activity of a more potent glycoside
      echinoside A (1) in HepG2 cells was further investigated by determining its
      effect on the morphology, mitochondrial transmembrane potential (Deltapsim) and
      mRNA expression levels of the apoptosis-related genes. The results showed that
      the number of glycosyl residues in sugar chains and the side chain of aglycone
      could affect their cytotoxicity towards tumor cells and selective cytotoxicity. 1
      significantly inhibited cell viability and induced apoptosis in HepG2 cells. 1
      also markedly decreased the Deltapsim and Bcl-2/Bax mRNA express ratio, and up
      regulated the mRNA expression levels of Caspase-3, Caspase-8 and Caspase-9 in
      HepG2 cells. Therefore, 1 induced apoptosis in HepG2 cells through both intrinsic
      and extrinsic pathway. These findings could potentially promote the usage of
      these glycosides as leading compounds for developing new antitumor drugs. 

PMID- 25062510
TI  - MUC1 expression in fallopian tubes of women with hydrosalpinx.
AB  - OBJECTIVE: To analyze the expression of MUC1 in Fallopian tubes with or without
      hydrosalpinx, using four different types of antibody. STUDY DESIGN: In a case
      control study, immunohistochemical expression of MUC1 was examined in Fallopian
      tubes derived from women with hydrosalpinx (n=10) and normal controls (n=10).
      Four different antibodies were used for the detection of both extracellular
      (214D4, HMFG1, VPM654) and intracellular (EPR1023) MUC1 epitopes. Staining
      intensity was measured with ImageJ software. Expression of MUC1 mRNA was
      quantified by quantitative RT-PCR. Statistical analysis was performed with
      Student t-test (mean +/- SD) and Mann-Whitney U-test (median [range]). RESULTS:
      The mean (+/-SD) and median [range] intensity of MUC1 in controls vs.
      hydrosalpinx were: 214D4-67.5 +/- 11.3 vs. 74.8 +/- 14.69 (P=0.22); HMFG1-95.3
      [642-1079] vs. 97.0 [502-1550] (P=0.91); VPM654-41.1 [314-914] vs. 46.0 [390
      1424] (P=0.1); EPR1023-24.7 +/- 7.3 vs. 57.4 +/- 31.3 (P=0.01). MUC1 mRNA was
      0.16 [008-05] vs. 0.09 [005-019] (P=0.06). Ectodomains and mRNA of MUC1 are
      unchanged in tubes from hydrosalpinx patients. In contrast, immunodetection of
      the MUC1 cytoplasmic tail is enhanced in tubes from hydrosalpinx. CONCLUSION:
      Fallopian tubes with hydrosalpinx have a selective accumulation of MUC1
      cytoplasmic tail, but not difference in the ectodomain.

PMID- 25062511
TI  - Detection of east/central/south African genotype of chikungunya virus in Myanmar,
      2010.
AB  - In 2010, chikungunya virus of the East Central South African genotype was
      isolated from 4 children in Myanmyar who had dengue-like symptoms. Phylogenetic
      analysis of the E1 gene revealed that the isolates were closely related to
      isolates from China, Thailand, and Malaysia that harbor the A226V mutation in
      this gene. 

PMID- 25062512
TI  - The impact of the embryo quality on the risk of multiple pregnancies.
AB  - The aim of the present study was to determine the chance of pregnancy and the
      risk of multiple pregnancies taking into account the number and quality of
      transferred embryos in patients >36 years old or <=36 years old. For this study,
      1497 patients undergoing intra-cytoplasmic sperm injection (ICSI) cycles in a
      private assisted reproduction centre were split into groups according to the
      number and quality of the transferred embryos on the third or fifth day of
      development. The pregnancy rate and multiple pregnancy rate were compared between
      the embryo quality groups in patients <36 years old or >=36 years old. In
      patients <36 years old, for the day 3 embryo transfer, no significant difference
      was noted in the pregnancy rate when the groups were compared. However the
      multiple pregnancy rate was increased by the transfer of an extra low-quality
      embryo (17.1 versus 28.2%, P = 0.020). For day 5 embryo transfer, the transfer of
      an extra blastocyst significantly increased the pregnancy rate (36.0 versus
      42.4%, P < 0.001) and the multiple pregnancy rate (4.4 versus 16.9%, P < 0.001).
      In older patients, no significant difference was noted in the pregnancy rate when
      the groups were compared. However, when an extra low-quality embryo was
      transferred, a significantly increased rate of multiple pregnancies was observed
      for day 3 (18.2 versus 26.4%, P = 0.049) and day 5 embryo transfers (5.2 versus
      16.1%, P < 0.001). In conclusion, the transfer of an extra low-quality embryo may
      increase the risk of a multiple pregnancy. In younger patients, the transfer of
      an extra low-quality blastocyst may also increase the chance of pregnancy. 

PMID- 25062513
TI  - Perinatal substance abuse and neonatal abstinence.

PMID- 25062514
TI  - BirthTOOLS.org: a resource for nurses.

PMID- 25062515
TI  - Caring for the infant with neonatal abstinence syndrome in a community-based
      setting.

PMID- 25062516
TI  - Water, water everywhere ... or perhaps not? Informed consent and risk management
      for underwater birth.

PMID- 25062518
TI  - Psychosocial interventions for substance use during pregnancy.
AB  - Psychosocial and behavioral interventions are used to address substance use and
      dependence during pregnancy, having particular value when providers and pregnant
      women are seeking to minimize drug exposures to the fetus. Numerous factors,
      including difficulty recruiting participants and the ethical challenges to
      conducting randomized controlled trials with women during pregnancy, have limited
      research in this area. The existing literature, however, does contain early
      investigations into the practicality and efficacy of contingency management,
      motivational support, and cognitive behavioral therapies adapted for pregnant
      women. This article describes these approaches to treatment, summarizes
      programmatic examples, and highlights the role nurses may play with this special
      population. 

PMID- 25062519
TI  - Buprenorphine for the treatment of opioid dependence in pregnancy.
AB  - The treatment of opioid dependence during pregnancy has historically consisted of
      either medication-assisted withdrawal or maintenance treatment with methadone.
      Buprenorphine maintenance treatment is emerging as a treatment during pregnancy
      with distinct benefits for the neonate and the pregnant woman. Buprenorphine is
      effective in decreasing the risk of relapse in pregnant women. In addition,
      prenatal use of buprenorphine appears to decrease the severity and duration of
      neonatal abstinence syndrome as compared with methadone maintenance. Management
      of buprenorphine includes initiation and maintenance treatment as well as careful
      planning for pain control during and after delivery and prevention of postpartum
      relapse risk. Only very small amounts of buprenorphine enter breast milk, making
      it a good option for those who elect to breast-feed. There is evidence that
      emerging collaborative care models are effective ways to deliver buprenorphine
      maintenance treatment, although more investigation is needed to generalize this
      to the obstetric setting. 

PMID- 25062520
TI  - Early intervention in pregnant women with elevated anxiety and depressive
      symptoms: efficacy of a cognitive-behavioral group program.
AB  - To examine whether a cognitive-behavioral group program among pregnant women with
      elevated levels of anxiety or depression may reduce anxious and depressive
      symptoms and has a positive impact on risk factors for anxiety disorders and
      depression. A total of 753 participants were recruited. After completion of the
      clinical standardized interview, 160 participants were randomized to an
      intervention group or a control condition. Psychometric assessments took place at
      T1 (preintervention), T2 (antenatal follow-up), and T3 (3 months postpartum).
      Analyses included women who took part in all 3 assessments (intervention group, N
      = 21; control group, N = 53). The subjective program evaluation by the
      participants was highly positive, but with the exception of a short-term effect
      on the quality of an intimate partnership (F1/67 = 4.056; P < .05], intervention
      effects on anxiety or depressive symptoms were not found. However, there was an
      intervention effect 3 months postpartum for participants with high depressive
      symptoms at T1 (Edinburgh Postnatal Depression Scale score of >=10) (F1/69 =
      5.410; P < .05). The results argue against a general efficacy of a cognitive
      behavioral group program for pregnant women with rather low levels of anxiety and
      depression. For women with higher depressive symptoms during pregnancy, a
      cognitive-behavioral group program may have a positive impact on the course of
      depressive symptoms during the postpartum period. 

PMID- 25062521
TI  - Identification and management of prescription drug abuse in pregnancy.
AB  - Prescription drug abuse is a growing problem in the United States and many other
      countries. Estimates of prescription drug abuse rates during pregnancy range from
      5% to 20%. The primary prescription drugs designated as controlled drugs with
      abuse potential in pregnancy are opiates prescribed for pain, benzodiazepines
      prescribed for anxiety, and stimulants prescribed for attention
      deficit/hyperactivity disorder. Prescription drugs are obtained for abuse through
      diversion methods, such as purchasing them from others or by doctor shopping. The
      use of prescription drugs puts both the mother and the fetus at high risk during
      pregnancy. Identification of women who are abusing prescription drugs is
      important so that treatment can be ensured. It is crucial for healthcare
      professionals to use a multidisciplinary approach and be supportive and maintain
      a good rapport with pregnant women who abuse prescription drugs. Management
      includes inpatient hospitalization for detoxification and withdrawal symptoms,
      and in the case of opiate abuse, opiate maintenance is recommended for pregnant
      women for the duration of their pregnancy to reduce relapse rates and improve
      maternal and fetal outcomes. Other recommendations include referral for support
      groups and supportive housing. 

PMID- 25062522
TI  - Care of the infant with neonatal abstinence syndrome: strength of the evidence.
AB  - There is little empirical evidence that guides management of infants with
      neonatal abstinence syndrome. The standard of care first described in the 1970s
      is still prevalent today, although it has never been tested in this population.
      Standard of care interventions include decreasing external stimulation, holding,
      nonnutritive sucking, swaddling, pressure/rubbing, and rocking. These
      interventions meet the goals of nonpharmacologic interventions, which are to
      facilitate parental attachment and decrease external stimuli. Many nursing
      interventions used in infants with neonatal abstinence syndrome have been tested
      in low-birth-weight infants, whose treatment often includes the same goals. Those
      interventions include music therapy, kangaroo care, massage, and use of
      nonoscillating water beds. Nursing attitude has also been shown to be impactful
      on parental attachment. The American Academy of Pediatrics recommends breast
      feeding in infants whose mothers are on methadone who do not have any other
      contraindication. It also provides guidelines for pharmacologic management but
      cannot provide specific recommendations about a standard first dose, escalation,
      or weaning schedule. Buprenorphine has some evidence about its safety in newborns
      with neonatal abstinence syndrome, but high-powered studies on its efficacy are
      currently lacking. There are many opportunities for both evidence-based projects
      and nursing research projects in this population. 

PMID- 25062523
TI  - An overview of clinical tools used to assess neonatal abstinence syndrome.
AB  - Several clinical tools have been developed to quantify the severity of withdrawal
      signs and symptoms exhibited by infants born to substance-using mothers. Scores
      from the systematic assessments are used to guide treatment of infants with
      moderate to severe clinical signs. This article provides an overview of published
      assessment tools developed for infants with neonatal abstinence syndrome. Nurses
      caring for infants at risk for neonatal abstinence syndrome should be
      knowledgeable about the tools used to evaluate these infants and guide their
      treatment. The ideal assessment tool should be published and include item
      definitions and a protocol for administering the tool. Nurses need education and
      training to achieve competency and interobserver reliability in the use of a
      selected tool. Tool-specific materials should be used to standardize training and
      improve accuracy in assessments. Competent and knowledgeable nurses play a
      critical role in improving outcomes for infants with neonatal abstinence
      syndrome. 

PMID- 25062524
TI  - Assessing neonates for neonatal abstinence: are you reliable?
AB  - Nationally, there has been a steady increase in the number of infants born with
      neonatal abstinence syndrome or drug withdrawal. Many of these infants remain in
      the hospital because their signs of withdrawal require pharmacologic management.
      The length of hospital stay can range from 1 week to several months depending on
      the severity of withdrawal. One way to decrease the length of stay and reduce the
      cost of care is to discharge the infant from the hospital sooner. To discharge
      infants sooner, their neonatal abstinence syndrome must be accurately assessed so
      that appropriate pharmacologic management can be administered. One way to
      increase the accuracy of assessing withdrawal signs is to implement an
      interobserver reliability protocol. This approach will allow healthcare
      professionals to gain consistency and accuracy in assessing infants for signs of
      withdrawal that may facilitate earlier discharge from the hospital. 

PMID- 25062525
TI  - Neonatal abstinence syndrome: evaluating the effectiveness of an evidence-based
      multidisciplinary care approach.
AB  - An evidence-based, multidisciplinary neonatal abstinence syndrome protocol was
      developed using a stepwise continuous quality improvement (CQI) approach with the
      goal of standardizing care procedures for these infants. A retrospective
      secondary data analysis was performed to evaluate the differential effects of
      each step of the CQI project on 4 key clinical outcome measures: length of stay
      (total and post-opioid wean), weaning time from opioids, and use of adjunct
      medications. Data were analyzed from 386 newborn infants with a diagnosis of
      neonatal abstinence syndrome undergoing treatment in a level III neonatal
      intensive care unit. After implementation of a pharmacologic weaning protocol as
      a foundational first step of the CQI project, the weaning time from opioids
      remained stable throughout each of the subsequent CQI steps (P = .905). The
      overall total neonatal intensive care unit length of stay was reduced by 10.35
      days (P = .002), and the length of neonatal intensive care unit stay after
      completing wean from opioids was reduced by 2.79 days (P < .001). Use of adjunct
      medications also decreased from 30.1% of infants at the initiation of the CQI
      project to 24.5% at the completion of the project (P = .020). These findings
      indicate that this multidisciplinary treatment approach led to an overall
      improved efficiency of both opioid weaning and symptom management for these
      infants. 

PMID- 25062526
TI  - The breast can be lethal.

PMID- 25062529
TI  - Effect of NaCl on ionic content and distribution in suspension-cultured cells of
      the halophyte Sonneratia alba versus the glycophyte Oryza sativa.
AB  - The effect of a high concentration of NaCl on the intra- (cytoplasmic matrix and
      vacuole) and extracellular (cell wall) distribution of Na, Cl, K, Mg, Ca, S, and
      P was investigated in suspension-cultured cells of the mangrove halophyte
      Sonneratia alba and compared to cultured cells of glycophytic rice (Oryza
      sativa). No significant differences were observed in ultrastructural features of
      cluster cells of both species cultured with and without 50mM NaCl. Quantitative X
      ray microanalysis of cryosections of the cells cultured in the presence of 50mM
      NaCl showed that the Na concentration ([Na]) and Cl concentration ([Cl])
      significantly increased in all three cell components measured. In S. alba, the
      [Na] was highest in the vacuole and lowest in the cytoplasmic matrix, while the
      [Cl] was highest in the cell wall and lowest in the cytoplasmic matrix. In O.
      sativa, however, the [Na] and [Cl] were highest in the cell wall, and the [Na]
      was lowest in the cytoplasmic matrix. Thus, the possible activities for Na and Cl
      transport from the cytoplasmic matrix into the vacuole were greater in S. alba
      than in O. sativa, suggesting that halophilic mangrove cells gain salt tolerance
      by transporting Na and Cl into their vacuoles. In O. sativa, the addition of NaCl
      to the culture medium caused no significant changes to the intracellular
      concentrations of various elements, such as K, P, S, Ca, and Mg, which suggests
      the absence of a direct relationship with the transport Na and Cl. In contrast, a
      marked decrease in the Ca concentration ([Ca]) in the cytoplasmic matrix and
      vacuole and an approximately two-fold increase in the P concentration ([P]) in
      the cytoplasmic matrix were found in S. alba, suggesting that the decrease in the
      [Ca] is related to the halophilic nature of S. alba (as indicated by the inward
      movement of Na(+) and Cl(-)). The possible roles of a Na(+)/Ca(2+) exchange
      mechanism in halophilism and the effect of the [P] on the metabolic activity
      under saline conditions are discussed. 

PMID- 25062530
TI  - A structure-reactivity relationship driven approach to the identification of a
      color test protocol for the presumptive indication of synthetic cannabimimetic
      drugs of abuse.
AB  - The number of analyses of synthetic cannabimimetic drugs of abuse by forensic
      laboratories in the United States grew rapidly from 2010 to 2012 and then
      declined somewhat in 2013. In 2010, according to the National Forensic Laboratory
      Information System (NFLIS), 3,287 reports by federal, state and local forensic
      laboratories were identified as containing synthetic cannabinoids. In 2011 and
      2012, the numbers increased to 23,693 and 42,503, respectively. 27,119 reports
      were identified in 2013. Several commonly encountered structural sub-classes of
      these synthetic designer drugs, namely the naphthoylindoles, benzoylindoles,
      phenylacetylindoles, and cyclopropoylindoles contain a ketone functional group.
      The Duquenois-Levine color test for the presumptive identification of classical
      cannabinoids such as Delta(9)-tetrahydrocannabinol is negative for the synthetic
      cannabimimetics. The van Urk color test for the presumptive identification of
      indole containing drugs of abuse is also negative for these compounds. The use of
      2,4-dinitrophenylhydrazine as an alternative color test reagent (targeting the
      keto moiety rather than the indole) for presumptive identification of these
      classes of drugs was investigated. 

PMID- 25062531
TI  - Raman spectroscopy and capillary electrophoresis applied to forensic colour
      inkjet printer inks analysis.
AB  - Forensic laboratories are increasingly engaged in the examination of fraudulent
      documents, and what is important, in many cases these are inkjet-printed
      documents. That is why systematic approaches to inkjet printer inks comparison
      and identification have been carried out by both non-destructive and destructive
      methods. In this study, micro-Raman spectroscopy and capillary electrophoresis
      (CE) were applied to the analysis of colour inkjet printer inks. Micro-Raman
      spectroscopy was used to study the chemical composition of colour inks in situ on
      a paper surface. It helps to characterize and differentiate inkjet inks, and can
      be used to create a spectra database of inks taken from different cartridge
      brands and cartridge numbers. Capillary electrophoresis in micellar
      electrophoretic capillary chromatography mode was applied to separate colour and
      colourless components of inks, enabling group identification of those components
      which occur in a sufficient concentration (giving intensive peaks). Finally, on
      the basis of the obtained results, differentiation of the analysed inks was
      performed. Twenty-three samples of inkjet printer inks were examined and the
      discriminating power (DP) values for both presented methods were established in
      the routine work of experts during the result interpretation step. DP was found
      to be 94.0% (Raman) and 95.6% (CE) when all the analysed ink samples were taken
      into account, and it was 96.7% (Raman) and 98.4% (CE), when only cartridges with
      different index numbers were considered. 

PMID- 25062532
TI  - Postmortem 31P magnetic resonance spectroscopy of the skeletal muscle: alpha
      ATP/Pi ratio as a forensic tool?
AB  - PURPOSE: Phosphor magnetic resonance spectroscopy ((31)P MRS) is an established
      method for metabolic examinations of resting and exercising skeletal muscle. So
      far, there are few MRS investigations of human corpses. The aim of this study was
      to investigate the temporal postmortem pattern of phosphor metabolites in the
      adductor magnus muscle and to check the value of MRS as a forensic tool,
      especially for the determination of the time of death. MATERIAL AND METHODS:
      Eight corpses, died of natural cause, were examined (5 males, 3 females; age:
      73+/-7 y, weight 65.8+/-15.9 kg). A control group of 3 subjects (2 males, 1
      female, mean age: 51+/-24 y, range: 24-69 y, mean body weight: 84.0+/-16.5 kg)
      was examined at a single time point as well. (31)P MRS was performed on a 1.5 T
      MRI (TR 700 ms, TE 0.35 ms, averages 256, flip angle 90 degrees ). A standard
      (31)P/(1)H heart/liver coil was employed (receiver coil diameter 12 cm). The
      (31)P MRS scans were repeated in intervals of 1 h over a period from 4.5 to 24 h
      postmortem (p.m.). The core temperature was rectally measured throughout the MRI
      examination. RESULTS: The mean core temperature decreased from 36.0 degrees C to
      25.7 degrees C. In vivo and ex vivo spectra showed characteristic differences,
      especially the PCr metabolite was no longer detectable after 10 h p.m. The alpha
      ATP/Pi ratio decreased with time from 0.445 to 0.032 over 24 h p.m. CONCLUSION:
      There is a characteristic postmortem time pattern of the phosphor metabolites.
      Especially the acquired alpha-ATP/Pi ratio could be described by a significant
      exponential time course (r(2)=0.92, p<0.001). (31)P MRS might be added to the
      postmortem imaging methods.

PMID- 25062533
TI  - Are chronic diseases related to height? Results from the Portuguese National
      Health Interview Survey.
AB  - This paper analyze the association between height and chronic diseases in
      Portugal and the extent to which this relationship is mediated by education. The
      sample upon which the analysis is based comprised those participants in the
      2005/2006 Portuguese National Health Interview Survey (n=28,433) aged 25-79.
      Logistic regressions measured the association of height with ten chronic
      diseases, adjusting for age, lifestyle, education, and other socioeconomic
      factors. Among women, an additional centimeter in stature significantly decreased
      the prevalence of asthma, chronic pain, and acute cardiac disease, by 0.057,
      0.221, and 0.033 percentage points, respectively. Also, mental disorders were
      significantly less prevalent in the last quartile of height. Among men, an
      additional centimeter in height was associated with a 0.074 lower prevalence of
      asthma, and men in the last quartile of height were significantly less at risk of
      acute cardiovascular disease. There was no significant association between height
      and the risk of diabetes, high blood pressure, cancer, and pulmonary diseases. As
      for the impact of education, women with a tertiary level were on average 5.3cm
      taller than those with no schooling; among men, the difference was almost 9cm.
      Adjusting for education reduced the height-related excess risk of ill health by
      36% on average among men, and by 7% among women. The analysis indicates that
      there is a significant association of height with several chronic conditions, and
      that education plays a mediating role in the height-health connection. By
      emphasizing the role of height and education as determinants of chronic
      conditions, this paper also highlights the role of conditions related to
      childhood health and socioeconomic background. 

PMID- 25062534
TI  - Pulmonary infection and colonization with nontuberculous mycobacteria, Taiwan,
      2000-2012.
AB  - We analyzed samples from 13,652 patients who had respiratory cultures positive
      for mycobacteria in Taiwan during 2000-2012 and found that 56.9% were positive
      for nontuberculous mycobacteria (NTM). Whereas annual prevalence of tuberculosis
      decreased during the study period, prevalence of NTM disease and colonization
      increased, particularly among older patients and male patients. 

PMID- 25062535
TI  - The use of the Addenbrooke's Cognitive Examination in a community memory clinic.

PMID- 25062536
TI  - Lithium species in electrochemically lithiated and delithiated silicon
      oxycarbides.
AB  - The work described herein deals with efforts to make a persuasive correlation
      between structural characteristics and electrochemical lithium storage for a
      silicon oxycarbide prepared from poly(methylhydrogensiloxane) and divinylbenzene.
      Structural characterization reveals that the silicon oxycarbide includes excess
      free carbon in an amorphous network. The reversibility of lithiation and
      delithiation in the silicon oxycarbide reaches 74% between 0.005 and 3 V relative
      to lithium at the first cycle but falls to only ca. 30% between 0.4 and 3 V. We
      found two resonances at 0 and 2.4 ppm in the (7)Li magic angle spinning nuclear
      magnetic resonance spectrum of the silicon oxycarbide lithiated to 0.4 V, whose
      contributions are 67 and 33%, respectively, and thus are in good agreement with
      the reversibility observed between 0.4 and 3 V. The fully lithiated silicon
      oxycarbide shows a single resonance at ca. 3-9 ppm, which tends to broaden at
      lower temperatures to -120  degrees C, whereas the fully delithiated silicon
      oxycarbide has a single resonance at 0 ppm. These results indicate that both
      reversible and irreversible lithium species have ionic natures. The Li K edge in
      electron energy loss spectroscopy does not show clearly any identified near-edge
      fine structures in the inner part of the silicon oxycarbide after delithiation.
      Near the surface, on the other hand, LiF and oxygen- and phosphorus-containing
      compounds were found to be the major constituents of a solid electrolyte
      interface (SEI) layer. Over repeated lithiation and delithiation, the SEI layer
      appears to become thick, which should in part trigger capacity fading. 

PMID- 25062538
TI  - Co-metabolic degradation of tetrabromobisphenol A by novel strains of Pseudomonas
      sp. and Streptococcus sp.
AB  - Three strains capable of rapidly degrading TBBPA by co-metabolism and utilizing
      formate as the carbon source, named as J-F-01, J-F-02, and J-F-03, respectively,
      were isolated from enrichment cultures, which have been treated with 0.5mg/L
      TBBPA for 240 d. Based on morphology and 16S rRNA gene sequence analysis, both J
      F-01 and J-F-02 were determined to Pseudomonas sp., while J-F-03 was identified
      as Streptococcus sp. A shorter half-life (6.1d) of TBBPA was observed in pure
      culture of J-F-03 when compared with J-F-01 (22.5d) and J-F-02 (13.6d).
      Surprisingly, the degradation of TBBPA was significantly enhanced by the mixed
      culture of J-F-02 and J-F-03. The optimal degradation conditions for the mixed
      cultures were determined. Under the optimal conditions, TBBPA (0.5mg/L) was
      completely metabolized by the mixed culture within ten days. Moreover, bromide
      and the metabolisms were detected, and a possible metabolic pathway was deduced
      from the detection of metabolite production patterns.

PMID- 25062537
TI  - Effects of azide on electron transport of exoelectrogens in air-cathode microbial
      fuel cells.
AB  - The effects of azide on electron transport of exoelectrogens were investigated
      using air-cathode MFCs. These MFCs enriched with azide at the concentration
      higher than 0.5mM generated lower current and coulomb efficiency (CE) than the
      control reactors, but at the concentration lower than 0.2mM MFCs generated higher
      current and CE. Power density curves showed overshoot at higher azide
      concentrations, with power and current density decreasing simultaneously.
      Electrochemical impedance spectroscopy (EIS) showed that azide at high
      concentration increased the charge transfer resistance. These analyses might
      reflect that a part of electrons were consumed by the anode microbial population
      rather than transferred to the anode. Bacterial population analyses showed azide
      enriched anodes were dominated by Deltaproteobacteria compared with the controls.
      Based on these results it is hypothesized that azide can eliminate the growth of
      aerobic respiratory bacteria, and at the same time is used as an electron
      acceptor/sink. 

PMID- 25062539
TI  - Exploring redox-mediating characteristics of textile dye-bearing microbial fuel
      cells: thionin and malachite green.
AB  - Prior studies indicated that biodecolorized intermediates of azo dyes could act
      as electron shuttles to stimulate wastewater decolorization and bioelectricity
      generation (WD&BG) in microbial fuel cells (MFCs). This study tended to explore
      whether non-azo textile dyes (i.e., thionin and malachite green) could also own
      such redox-mediating capabilities for WD&BG. Prior findings mentioned that OH
      and/or NH2 substitute-containing auxochrome compounds (e.g., 2-aminophenol and
      1,2-dihydroxybenzene) could effectively mediate electron transport in MFCs for
      simultaneous WD&BG. This work clearly suggested that the presence of electron
      mediating textile dyes (e.g., thionin and malachite green (MG)) in MFCs is
      promising to stimulate color removal and bioelectricity generation. That is,
      using MFCs as operation strategy for wastewater biodecolorization is economically
      promising in industrial applications due to autocatalytic acceleration of
      electron-flux for WD&BG in MFCs. 

PMID- 25062540
TI  - Effect of liquid hot water pre-treatment on sugarcane press mud methane yield.
AB  - Sugarcane press mud was pretreated by liquid hot water (LHW) at different
      temperatures (140-210  degrees C) and pre-treatment times (5-20 min) in order to
      assess the effects on the chemical oxygen demand (COD) solubilisation, inhibitors
      formation and methane yield. The experimental results showed that a high degree
      of biomass solubilisation was possible using LHW. Higher methane yields were
      obtained at lower severities (log(Ro) = 2.17-2.77) with (i) mild temperatures
      (140-150  degrees C) and long contact times (12.5 min, 20 min) or (ii) mild
      temperatures (175  degrees C) with short contact time (2 min). The highest
      increase in methane yield (up to 63%) compared to the untreated press mud was
      found at 150  degrees C for 20 min. At temperatures of 200  degrees C and 210 
      degrees C, low methane efficiency was attributed to the possible formation of
      refractory compounds through the Maillard reaction.

PMID- 25062541
TI  - A comparative study on different metal loaded soybean milk by-product 'okara' for
      biosorption of phosphorus from aqueous solution.
AB  - Cationization of agricultural by-products using metal salts is widely used to
      activate their phosphorous capture ability. This study developed three kinds of
      new metal loaded soybean milk by-product 'okara' for phosphorus biosorption. A
      comparative study among these biosorbents was carried out with respect to their
      performances in terms of affinity, stability and reusability. Zirconium loaded
      okara (ZLO) was found to have the highest affinity towards PO(4)(3-) anions
      (47.88 mg/g), followed by iron/zirconium loaded okara--IZLO (40.96 mg/g) and iron
      loaded okara--ILO (16.39 mg/g). ZLO was successfully desorbed with 0.2M NaOH and
      activated with 0.1 HCl prior to the next cycle. After five consecutive cycles,
      the efficiency of both adsorption and desorption of ZLO remained about 85% whilst
      no Zr(IV) leakage was observed. Conversely, IZLO and ILO suffered from vital
      short comings such as high metal release and/or sharp reduction in PO4(3-)
      sequestering capability after multi operation cycles.

PMID- 25062542
TI  - Enhancement of anaerobic digestion of shredded grass by co-digestion with sewage
      sludge and hyperthermophilic pretreatment.
AB  - Anaerobic co-digestion of shredded grass with sewage sludge was investigated
      under various temperature conditions. The conversion of grass to methane was
      difficult to achieve under mesophilic conditions, while its methane yield was
      0.19 NL/g VS-grass under thermophilic conditions. The mixture ratio of grass to
      sludge affected the methane yield, and the highest synergistic effect was
      obtained at a C/N ratio of around 10. In a continuous experiment,
      hyperthermophilic (80  degrees C) pretreatment promoted a methane yield of 0.34
      NL/g VS-mixture, higher than that under mesophilic and thermophilic conditions
      (0.20 and 0.30 NL/g VS-mixture, respectively). A batch experiment with
      hyperthermophilic pretreatment showed that 3 days of treatment was sufficient for
      subsequent methane production, in which the highest dissolution of particulate
      COD, carbohydrate and protein was 25.6%, 33.6% and 25.0%, respectively.

PMID- 25062543
TI  - Management of acute concussion in a deployed military setting.
AB  - OPINION STATEMENT: The DoD has established clinical guidelines and policies
      creating a system of care for the management of battlefield concussion. Within
      these instructions, medical providers have standardized guidance for screening
      and diagnosing concussion, along with guidelines for treating common concussion
      symptoms. Underlying these policies is the principle that concussion is an
      important injury, and SMs need to be removed from combat during the acute period
      to ensure full recovery before return to duty. As our understanding of concussion
      advances, the DoD will incorporate these advances into the current system of
      care, ensuring that SMs have the highest level of care possible for concussions
      sustained on the battlefield.

PMID- 25062544
TI  - Non-epileptic paroxysmal events mimicking seizures.
AB  - The diagnosis of epilepsy rests on a detailed history and examination. The main
      focus of such a history is to exclude the possibility of non-epileptic paroxysmal
      events. An incorrect diagnosis of epilepsy can potentially lead to physical,
      psychological and financial harm to the child and the family. A wide range of non
      epileptic paroxysmal events can occur in children. The differentiation of a
      seizure mimic from a seizure relies solely on a proper history and review of
      video recordings. Investigations rarely help in the diagnosis of these events. An
      early and timely diagnosis and proper parental counseling helps avoiding
      unnecessary investigations, treatment and allays parental anxiety. The article
      reviews the common non-epileptic paroxysmal events in children, emphasizing
      clinically relevant points. 

PMID- 25062545
TI  - The anatomy of visuospatial construction revealed by lesion-symptom mapping.
AB  - Visuospatial construction is a complex cognitive operation that is composed of a
      purely constructional component (visuoconstruction proper), and visuoperceptive,
      attentional, and decision-making components. The anatomical correlates of
      visuospatial construction and its cognitive subcomponents are poorly understood.
      The purpose of the present study was to determine the anatomical correlates of
      visuospatial construction by applying lesion-symptom mapping in a cohort of 111
      patients with first-ever ischemic stroke. We employed the Rey-Osterrieth Complex
      Figure (ROCF) copy test and the Judgment of Line Orientation (JLO); both tests
      measure visuoperception, while only the ROCF has a constructional component. We
      first performed assumption-free voxel-based lesion-symptom mapping, which
      revealed large shared right hemispheric correlates for the ROCF and JLO in the
      frontal lobe, superior temporal lobe, and supramarginal gyrus. These shared
      anatomical correlates reflect the visuoperceptive component of the ROCF and JLO.
      Anatomical correlates were discordant in the right superior parietal lobule, and
      angular and middle occipital gyri: lesions in these regions were associated with
      poor performance on the ROCF, but not the JLO. Secondly, these findings were
      reproduced with a region of interest-based analysis that yielded a statistically
      significant correlation between infarct volume in the right inferior and superior
      parietal, angular and middle occipital cortices, and poor performance on the
      ROCF, but not the JLO. This discordance in anatomical correlates of the ROCF and
      JLO reflects the visuoconstructive component of the ROCF. These findings provide
      new insights in the anatomical correlates of the visuoperceptive and
      visuoconstructive components of the ROCF and provide evidence for a crucial role
      of the right inferior and superior parietal, angular and middle occipital gyri in
      visuoconstruction proper. 

PMID- 25062546
TI  - Polybrominated diphenyl ethers listed as Stockholm Convention POPs, other
      brominated flame retardants and heavy metals in e-waste polymers in Nigeria.
AB  - Polybrominated diphenyl ethers (PBDEs) were the first brominated persistent
      organic pollutants (POPs) listed in the Stockholm Convention. Parties to the
      convention are currently establishing inventories for developing action plans for
      the environmentally sound management of PBDE-containing materials. The major use
      of commercial octabromodiphenyl ether (c-OctaBDE) has been in casings from
      cathode ray tube (CRT) TVs and computer monitors. Large quantities of used e
      waste and electronic equipment have been exported to developing countries with
      Nigeria being a major importer in Africa. The casings from 382 TVs and computers
      imported from major world regions to Nigeria were sampled in backyards and waste
      dumps. The samples were screened with X-ray flourescence (XRF) for bromine and
      analysed by gas chromatography/ electron capture detection (GC/ECD) for
      brominated flame retardants (BFRs). A high proportion of the CRT casings (61 %)
      contained more than 10,000 ppm bromine from BFRs. Decabromodiphenyl ether
      (DecaBDE) was the major flame retardant used in TV sets and tetrabromobisphenol A
      (TBBPA) for computer CRTs.The screening suggests that average PBDE levels (of c
      OctaBDE + DecaBDE) in Nigerian-stockpiled CRT casings were 1.1 % for TV and 0.13
      % for PC CRTs. These are above the Restriction of Hazardous Substances (RoHS)
      limit and should be separated for RoHS compliant recycling. The Nigerian e-waste
      inventory of 237,000 t of CRT plastic would therefore contain approx. 594 t c
      OctaBDE and 1,880 t of DecaBDE. In Nigeria, as for most developing countries,
      there is currently no adequate e-waste management, plastic separation or
      destruction capacity. The data highlight the urgent need to develop
      environmentally sound management for this large material flow.

PMID- 25062547
TI  - Lead removal in rats using calcium alginate.
AB  - Lead (Pb) exposure, even at low levels, causes a variety of health problems. The
      aims of this study were to investigate the tissue distribution of lead in the
      bodies of rats, to evaluate lead removal from the internal organs and bones using
      calcium alginate in doses of 500, 200 and 100 mg/kg per day for 28 days and to
      assess the impact of calcium alginate on the level of essential elements. Lead
      (Pb), calcium (Ca), manganese (Mn), iron (Fe), copper (Cu) and zinc (Zn) levels
      in the blood, hearts, kidneys, livers and femurs of the experimental animals were
      measured using mass spectrometry with inductively coupled plasma. The results
      revealed that lead acetate exposure increased the levels of Pb in the blood and
      organs of the animals and significantly reduced contents of Ca, Mn, Fe, Cu and
      Zn. Treatment with calcium alginate in dose 500 mg/kg contributed to significant
      decreases in the amount of lead in the kidney, heart and bones of animals and a
      slight increase in the content of essential elements in the liver, kidneys and
      heart, although these changes were not significant. Decreasing of lead was not
      significant in the internal organs, bones and blood of animals treated with
      calcium alginate 200 and 100 mg/kg. Consequently, calcium alginate dose of 500
      mg/kg more efficiently removes lead accumulated in the body. Calcium alginate
      does not have negative effect on level of essential elements quite the contrary;
      reducing the levels of lead, calcium alginate helps normalize imbalances of Ca,
      Mn, Fe, Cu and Zn. The results of this study suggest that calcium alginate may
      potentially be useful for the treatment and prevention of heavy metal
      intoxications. 

PMID- 25062548
TI  - Assessment of long-term phosphorus retention in an integrated constructed wetland
      treating domestic wastewater.
AB  - Due to the nature of the phosphorus (P) removal mechanisms associated with
      constructed wetlands, the sustainability of P treatment is usually of high
      interest. As a result, a 4-year dataset from a typical multi-celled integrated
      constructed wetland (ICW) located at Glaslough in Co. Monaghan, Ireland was
      evaluated to determine the effects of long-term P loadings and hydrological
      inputs on P treatment. The ICW was intensively monitored year-round from February
      2008 through March 2012 for total P and molybdate reactive phosphate (MRP).
      Domestic wastewater was loaded at 16.4 +/- 0.96 g m(2) year(-1) for total P and
      11.2 +/- 0.74 g m(2) year(-1) for MRP. Average mass reductions over the
      monitoring period were 91.4 and 90.1%, respectively. The area-based kinetic
      coefficients (K(20)) of 11.8 for total P and 15.6 m year(-1) for MRP indicated a
      high area-specific retention rate. The ICW appeared to have a sustained capacity
      for P adsorption and retention, but the treatment was influenced mainly by
      external hydrological inputs and fluctuations in wastewater loadings. Linear
      regression analyses showed a reduction in mass retention of both total P and MRP
      with increased effluent flow volumes. Monthly mass reductions exceeded 90% when
      the effluent flow volumes were less than 200 m(3) day(-1). When monthly effluent
      flow volumes exceeded 200 m(3) day(-1), nonetheless, mass reductions became
      highly variable. Designs and management of ICW systems should adopt measures to
      limit external hydrological loadings in order to maintain sufficient P treatment.

PMID- 25062549
TI  - The ability of Typha domingensis to accumulate and tolerate high concentrations
      of Cr, Ni, and Zn.
AB  - The tolerance and removal efficiency of Typha domingensis exposed to high
      concentrations of Cr, Ni, and Zn in single and combined treatments were studied.
      Sediment and two plants were disposed in each plastic reactor. The treatments
      were 100 and 500 mg L(-1) of Cr, Ni, and Zn (single solutions); 100 mg L(-1) Cr +
      Ni + Zn (multi-metal solutions) and 500 mg L(-1) Cr + Ni + Zn (multi-metal
      solutions); and a control. Even though the concentrations studied were extremely
      high, simulating an accidental metal dump, the three metals were efficiently
      removed from water. The highest removal was registered for Cr. The presence of
      other metals favored Cr and did not favor Ni and Zn removal from water. After 25
      days, senescence and chlorosis of plants were observed in Ni and Comb500
      treatments, while Cr and Zn only caused growth inhibition. T. domingensis
      accumulated high metal concentrations in tissues. The roots showed higher metal
      concentration than submerged parts of leaves. Cr translocation to aerial parts
      was enhanced by the presence of Ni and Zn. Our results demonstrate that in the
      case of an accidental dump of high Cr, Ni, and Zn concentrations, a wetland
      system dominated by T. domingensis is able to retain metals, and the macrophyte
      is able to tolerate them the time necessary to remove them from water. Thus, the
      environment will be preserved since the wetland would act as a cushion. 

PMID- 25062550
TI  - Functional outcomes and patient satisfaction after vascularized osteocutaneous
      scapula flap reconstruction of the mandible in patients with benign or cancerous
      tumours.
AB  - Pre- and postoperative longitudinal assessment of oral functions including
      masticatory force, masticatory ability with solids, speech intelligibility, and
      subjective satisfaction was conducted for patients who underwent vascularized
      osteocutaneous scapula flap reconstruction after mandibulectomy. Postoperative
      changes in oral function and patient satisfaction were examined in relation to
      tumour type (i.e., cancerous vs. benign). A change in masticatory force was
      associated with a reduction in the number of occlusal support zones after surgery
      and clearly differed by tumour type. Despite all patients showing reduced
      masticatory force postoperatively, all were satisfied with the improvements in
      eating and chewing, which were greater in patients with benign tumours than in
      those with cancerous tumours. Although both groups of patients expressed
      satisfaction with the aesthetic appearance after surgery, patients with cancerous
      tumours were more satisfied. However, both groups showed decreased speech
      intelligibility scores and lower satisfaction with speech after surgery.
      Preoperative support in the form of reassurance and helping to alleviate anxiety
      about postoperative appearance would be beneficial for all patients, with
      additional support provided based on the specific tumour type. 

PMID- 25062551
TI  - The diagnostic utility of biopsies from the submandibular and labial salivary
      glands in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's
      disease.
AB  - IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is characterized by serum
      IgG4 elevation and the infiltration of IgG4-positive plasma cells in glandular
      tissues. For definitive diagnosis of IgG4-DS, biopsies of local lesions are
      recommended to exclude Sjogren's syndrome (SS), malignant tumours, and similar
      disorders. In this study, we examined the diagnostic utility of submandibular
      gland (SMG) and labial salivary gland (LSG) biopsies in IgG4-DS. Fourteen
      patients presenting with swelling of the SMG (eight females and six males)
      underwent both SMG and LSG biopsies. The sensitivity, specificity, and accuracy
      of SMG biopsies were all 100.0%. In contrast, those of LSG biopsies were 69.2%,
      100.0%, and 71.4%, respectively. Thirty-three out of 61 LSG biopsies (54.1%) from
      all 14 patients were positive for the diagnostic criteria of IgG4-DS (IgG4
      positive/IgG-positive plasma cells >0.4). None of the patients experienced
      complications such as facial nerve palsy, sialocele, or hyposalivation. The
      IgG4/IgG ratio showed no significant correlation between the LSG and SMG. The
      final diagnosis was IgG4-DS in 13 patients and marginal zone B-cell lymphoma
      (MZL) in one. These results suggest that incisional biopsy of the SMG is useful
      and appropriate for the definitive diagnosis of IgG4-DS, while diagnosis by LSG
      biopsy alone requires more caution.

PMID- 25062552
TI  - Evaluating the impact of public health initiatives on trends in fecal occult
      blood test participation in Ontario.
AB  - BACKGROUND: Since the publication of two randomized controlled trials (RCT) in
      1996 demonstrating the effectiveness of fecal occult blood test (FOBT) in
      reducing colorectal cancer (CRC) mortality, several public health initiatives
      have been introduced in Ontario to promote FOBT participation. We examined the
      effect of these initiatives on FOBT participation and evaluated temporal trends
      in participation between 1994 and 2012. METHOD: Using administrative databases,
      we identified 18 annual cohorts of individuals age 50 to 74 years eligible for
      CRC screening and identified those who received FOBT in each quarter of a year.
      We used negative binomial segmented regression to examine the effect of
      initiatives on trends and Joinpoint regression to evaluate temporal trends in
      FOBT participation. RESULTS: Quarterly FOBT participation increased from 6.5 per
      1000 in quarter 1 to 41.6 per 1000 in quarter 72 (January-March 2012). Segmented
      regression indicated increases following the publication of the RCTs in 1996
      (Delta slope = 6%, 95% CI = 4.3-7.9), the primary care physician financial
      incentives announcement in 2005 (Delta slope = 2.2%, 95% CI = 0.68-3.7), the
      launch of the ColonCancerCheck (CCC) Program (Delta intercept = 35.4%, 95% CI =
      18.3 -54.9), and the CCC Program 2-year anniversary (Delta slope = 7.2%, 95% CI =
      3.9 - 10.5). Joinpoint validated these findings and identified the specific
      points when changes occurred. CONCLUSION: Although observed increases in FOBT
      participation cannot be definitively attributed to the various initiatives, the
      results of the two statistical approaches suggest a causal association between
      the observed increases in FOBT participation and most of these initiatives.

PMID- 25062553
TI  - A review of ecological effects and environmental fate of illicit drugs in aquatic
      ecosystems.
AB  - Although illicit drugs are detected in surface waters throughout the world, their
      environmental fate and ecological effects are not well understood. Many illicit
      drugs and their breakdown products have been detected in surface waters and
      temporal and spatial variability in use translates into "hot spots and hot
      moments" of occurrence. Illicit drug occurrence in regions of production and use
      and areas with insufficient wastewater treatment are not well studied and should
      be targeted for further study. Evidence suggests that illicit drugs may not be
      persistent, as their half-lives are relatively short, but may exhibit "pseudo
      persistence" wherein continual use results in persistent occurrence. We reviewed
      the literature on the ecological effects of these compounds on aquatic organisms
      and although research is limited, a wide array of aquatic organisms, including
      bacteria, algae, invertebrates, and fishes, have receptors that make them
      potentially sensitive to these compounds. In summary, illicit drugs occur in
      surface waters and aquatic organisms may be affected by these compounds; research
      is needed that focuses on concentrations of illicit drugs in areas of production
      and high use, environmental fate of these compounds, and effects of these
      compounds on aquatic ecosystems at the concentrations that typically occur in the
      environment. 

PMID- 25062554
TI  - Hemorrhagic stroke the first 30 days after an acute myocardial infarction:
      incidence, time trends and predictors of risk.
AB  - BACKGROUND/OBJECTIVES: Hemorrhagic stroke is a rare but serious complication
      after an acute myocardial infarction (AMI). The aims of our study were to
      establish the incidence, time trends and predictors of risk for hemorrhagic
      stroke within 30 days after an AMI in 1998-2008. METHODS: We collected data from
      the Register of Information and Knowledge about Swedish Heart Intensive Care
      Admissions (RIKS-HIA). All patients with a myocardial infarction 1998-2008 were
      included, n=173,233. The data was merged with the National Patient Register in
      order to identify patients suffering a hemorrhagic stroke. To identify predictors
      of risk we used Cox models. RESULTS: Overall the incidence decreased from 0.2%
      (n=94) in 1998-2000 to 0.1% (n=41) in 2007-2008. In patients with ST-elevation
      myocardial infarction the corresponding incidences were 0.4% (n=76) in 1998-2000
      and 0.2% (n=21) in 2007-2008, and after fibrin specific thrombolytic treatment
      0.6% and 1.1%, respectively, with a peak of 1.4% during 2003-2004. In total 375
      patients (0.22%) suffered a hemorrhagic stroke within 30 days of the AMI. The
      preferred method of reperfusion changed from thrombolysis to percutaneous
      coronary intervention (PCI). Older age (hazard ratio (HR) >65-<= 75 vs <= 65
      years 1.84, 95% confidence interval (CI) 1.38-2.45), thrombolysis (HR 6.84, 95%
      CI 5.51-8.48), history of hemorrhagic stroke (HR 12.52, CI 8.36-18.78) and prior
      hypertension (HR 1.52, CI 1.23-1.86) independently predicted hemorrhagic stroke
      within 30 days. CONCLUSIONS: The rate of hemorrhagic stroke within 30 days of an
      AMI has decreased by 50% between 1998 and 2008. The main reason is the shift in
      reperfusion method from thrombolysis to PCI.

PMID- 25062555
TI  - The type of atrial fibrillation recurrence after catheter ablation for persistent
      atrial fibrillation: what does it mean?

PMID- 25062556
TI  - Iloprost prevents doxorubicin mediated human cardiac progenitor cell depletion.

PMID- 25062557
TI  - To adjust, or not to adjust, that is the question.

PMID- 25062558
TI  - Reduction of myocardial inflammation with steroid is not necessarily associated
      with improvement in left ventricular function in patients with cardiac
      sarcoidosis: predictors of functional improvement.

PMID- 25062559
TI  - IgG4-related disease with effusive-constrictive pericarditis, tamponade, and
      hepatopathy: a novel triad.

PMID- 25062560
TI  - Red blood cell and platelet microparticles in myocardial infarction patients
      treated with primary angioplasty.
AB  - BACKGROUND: Red blood cell and platelet microparticles (RBCm and PLTm,
      respectively) have drawn research attention as to their potential prothrombotic
      and vasoconstrictive effects in experimental settings. However, the relevance of
      circulating microparticles in clinical settings is largely undetermined. METHODS:
      Circulating microparticles were quantified with a flow cytometric method in blood
      samples from consecutive STEMI patients after primary PCI. A matched cohort of
      healthy volunteers was used to derive reference values for comparison. STEMI
      patients were followed for 6 months for a composite clinical endpoint. RESULTS:
      Fifty-one STEMI patients (age 59.8 +/- 8.8 years) and 50 controls (age 56.2 +/-
      9.2 years; p=0.155) were enrolled. RBCm concentration was 18,198 +/- 6062/MUl in
      the reference cohort versus 33,740 +/- 21,169/MUl in STEMI patients (p<0.001).
      RBCm count was not correlated to total RBCs (standardized beta 0.018; p=0.861).
      PLTm did not differ between groups (17,529 +/- 16,292/MUl in STEMI patients
      versus 14,372 +/- 6211/MUl in controls; p=0.203). RBCm c-statistic was 0.832 (95%
      confidence interval 0.720 to 0.944), while PLTm prognostic value was not
      statistically significant (c-statistic 0.614, 95% confidence interval 0.444 to
      0.784). In the multivariate analysis, RBCm concentration was independently
      associated with the occurrence of the clinical endpoint, after adjustment for
      age, ejection fraction, serum creatinine and presence of diabetes (adjusted
      p=0.034). CONCLUSIONS: The present study demonstrates for the first time that
      erythrocyte microparticles are elevated in patients with STEMI treated with
      primary PCI, with levels approximately double those measured in a reference
      population of healthy volunteers, and their concentrations appear to be
      positively associated with adverse clinical events.

PMID- 25062561
TI  - Echocardiographic diagnosis of dissection of Valsalva sinus into anterior wall of
      left ventricle.

PMID- 25062562
TI  - Assessment of arterial elastance and ventricular-arterial coupling in patients
      with systemic lupus erythematosus.

PMID- 25062563
TI  - Heparin attenuates HMGB1 expression in arterial tissue subjected to limb
      ischemia/reperfusion.

PMID- 25062564
TI  - Preserved adrenal function in fully PCSK9-deficient subject.

PMID- 25062565
TI  - Association between serum chemokine CC-motif ligand 17 and coronary artery
      disease.

PMID- 25062566
TI  - Cardiac metabolism, inflammation, and peroxisome proliferator-activated receptors
      modulated by 1,25-dihydroxyvitamin D3 in diabetic rats.
AB  - BACKGROUND: High free fatty acid with reduced glucose utilization in diabetes
      mellitus (DM) impairs cardiac function. Peroxisome proliferator-activated
      receptors (PPARs) modulate myocardial lipid and glucose homeostasis. The active
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates oxidative stress and
      inflammation, which may play a key role in the modulation of PPARs. The aim of
      this study was to investigate whether 1,25(OH)2D3 can modulate the cardiac PPARs
      and fatty acid metabolism. METHODS: Electrocardiogram, echocardiogram, and
      Western blot analysis were used to evaluate cardiac fatty acid metabolism,
      inflammation, and PPAR isoform expression in Wistar-Kyoto (WKY) rats, DM rats,
      and DM rats treated with 1,25(OH)2D3. RESULTS: Compared to healthy rats, DM and
      1,25(OH)2D3-treated DM rats had lower body weight. DM rats had larger left
      ventricular end-diastolic diameter, and longer QT interval than healthy or
      1,25(OH)2D3-treated DM rats. Moreover, compared to healthy or 1,25(OH)2D3-treated
      DM rats, DM rats had fewer cardiac PPAR-alpha and PPAR-delta protein expressions,
      but had increased cardiac PPAR-gamma protein levels, tumor necrosis factor-alpha,
      interleukin-6, 5' adenosine monophosphate-activated protein kinasealpha2,
      phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase 1, PPAR
      gamma coactivator 1-alpha, cluster of differentiation 36, and diacylglycerol
      acyltransferase 2 protein expressions. CONCLUSIONS: 1,25(OH)2D3 significantly
      changed the cardiac function and fatty acid regulations in DM hearts, which may
      be caused by its regulations on cardiac PPARs and proinflammatory cytokines.

PMID- 25062567
TI  - Acetylated FoxO1 mediates high-glucose induced autophagy in H9c2 cardiomyoblasts:
      regulation by a polyphenol -(-)-epigallocatechin-3-gallate.
AB  - OBJECTIVE: FoxO1 acts as a pivotal transcription factor in insulin signaling.
      However, in hyperglycemia induced cardiac complications, whether FoxO1 is
      involved remains unclear. The goal of this study was to delineate the potential
      role of FoxO1 under high-glucose condition. MATERIALS/METHODS: We investigated
      insulin resistance and reactive oxygen species (ROS) generation in H9c2
      cardiomyoblasts after high-glucose exposure. A series of autophagy biomarkers
      were measured and further confirmed by LC3 turnover assay. Using gene silencing
      and overexpression experiments we dissected the molecular mechanisms of FoxO1
      regulated autophagy. We also tested the protective effect of (-)-epigallocatechin
      3-gallate (EGCG, a green tea-derived polyphenol) in high-glucose treated H9c2
      cardiomyoblasts. RESULTS: High-glucose elicited elevated ROS, autophagy and FoxO1
      abundance in cultured H9c2 cardiomyoblasts. Specifically, high-glucose
      significantly augmented the acetylated FoxO1 in cytosol. In line, compared with
      3A-FoxO1 (majorly localized in nuclei with a strong transcriptional activity),
      overexpression of WT-FoxO1 led to more intense elevated autophagy with enhanced
      acetylation of FoxO1. In addition, FoxO1 RNAi brought down autophagy induced by
      high-glucose. Intriguingly, EGCG successfully reversed ROS, autophagy and
      acetylated FoxO1 in high-glucose treated H9c2 cells. CONCLUSION: Our findings
      suggest that FoxO1, especially the acetylated form, regulates high-glucose
      induced autophagy in H9c2 cardiomyoblasts, which can be prevented by EGCG via a
      possible ROS-FoxO1 pathway.

PMID- 25062570
TI  - Improvement of nutritional care after colon surgery: the impact of early oral
      nutrition in the postanesthesia care unit.
AB  - PURPOSE: The purpose of this study was to evaluate the impact of implementing
      early oral nutritional supplements in the postanesthesia care unit (PACU) after
      colon surgery. DESIGN: A randomized controlled intervention study. METHODS:
      Patients admitted for elective colon surgery were randomly assigned to either a
      group receiving early oral nutritional supplements (n=24) or traditional
      treatment with water or lemonade (n=22) in the PACU. FINDING: On the second
      postoperative day, patients in the early nutritional supplement group had a
      higher cumulative intake of energy (P=.019) and protein (P=.015) compared with
      the traditional treatment. Postoperative nausea and vomiting, pain, length of
      stay in the PACU, and need of a nasogastric tube did not differ significantly
      between the groups. CONCLUSIONS: The nutritional course for patients undergoing
      colon surgery can be improved by implementing early oral nutritional supplements
      in the PACU.

PMID- 25062568
TI  - Geriatrics in medical students' curricula: questionnaire-based analysis.
AB  - BACKGROUND: Demographic development is accompanied by an increasingly aging
      society. Concerning medical education, the treatment of older people as well as
      the scientific research and exploration of ageing aspects in the coming years
      need to be considered. Aim of the study was to ascertain medical students'
      knowledge, interest, and attitudes regarding older patients and geriatric
      medicine. METHODS: Each participant completed a self-designed questionnaire. This
      questionnaire was based on three validated internationally recognised
      questionnaires ("Facts on Aging Quiz--FAQ", "Expectations Regarding Aging--ERA"
      and the "Aging Semantic Differential--ASD"). The inquiry and survey were
      performed at the beginning of the summer term in 2012 at the University of
      Regensburg Medical School. RESULTS: A total of n = 184/253 (72.7%) students
      participated in this survey. The results of the FAQ 25+ showed that respondents
      were able to answer an average of M = 20.4 of 36 questions (56.7%) correctly
      (Median, Md = 21; SD +/-6.1). The personal attitudes and expectations of ageing
      averaged M = 41.2 points on the Likert-scale that ranged from 0 to 100 (Md =
      40.4; SD +/-13.7). Respondents' attitudes towards the elderly (ASD 24) averaged M
      = 3.5 points on the Likert-scale (range 1-7, Md 3.6, SD +/-0.8). CONCLUSIONS: In
      our investigation, medical students' knowledge of ageing was comparable to
      previous surveys. Attitudes and expectations of ageing were more positive
      compared to previous studies. Overall, medical students expect markedly high
      cognitive capacities towards older people that can actively prevent cognitive
      impairment. However, medical students' personal interest in medicine of ageing
      and older people seems to be rather slight.

PMID- 25062571
TI  - Postdischarge nausea and vomiting: management strategies and outcomes over 7
      days.
AB  - PURPOSE: The purpose of this study is to determine patient management strategies
      and outcomes for self-care of postdischarge nausea and vomiting (PDNV). DESIGN:
      Prospective, comparative, descriptive, and longitudinal study. METHODS: The
      sample consisted of 248 patients aged 18 years or older undergoing a procedure
      requiring general anesthesia. Patients recorded incidence and severity of nausea
      and vomiting, the impact of symptoms, and actions taken to alleviate symptoms for
      7 days postdischarge. FINDINGS: The prevalence of PDNV was 56.9%. The methods
      used to relieve symptoms included antiemetic use by a minority and
      nonpharmacologic techniques of self-management by some. The effect of nausea on
      QOL, patient functioning, and patient satisfaction was significantly worse for
      those who experienced postdischarge nausea on all days. CONCLUSION: Patients with
      PDNV use minor self-care strategies to manage symptoms. The presence of PDNV
      affects overall quality of life, patient functioning, and patient satisfaction.

PMID- 25062572
TI  - Wacky Wednesday: use of distraction through humor to reduce preoperative anxiety
      in children and their parents.
AB  - PURPOSE: The purpose of this study was to determine the effect of distraction
      through humor on anxiety among children having outpatient surgery, and their
      parents. DESIGN: Quasi-experimental design using a nonrandomized control group.
      METHODS: The study assessed preoperative anxiety in child-parent dyads. The
      control group received usual care. The intervention group received the "Wacky
      Wednesday" (WW) intervention in which they entered an environment where employees
      were dressed in "wacky" attire and children and parents were provided with gifts
      and costume items. Anxiety scores, heart rate, and blood pressure were collected
      from patients and parents in both groups on admission and just before transfer to
      surgery. FINDINGS: Children who arrived for surgery on WW had significantly lower
      anxiety scores on admission than children in the control group. In addition,
      children and parents who received the WW intervention had significantly lower
      anxiety scores just before surgery than those in the control group. CONCLUSIONS:
      Humor and distraction are effective with children and parents in relieving
      preoperative anxiety.

PMID- 25062573
TI  - The best method to predict easy intubation: a quasi-experimental pilot study.
AB  - PURPOSE: To facilitate evaluation of the airway before endotracheal intubation,
      different scores have been developed, mainly to predict difficult airways.
      However, in anesthesia clinical practice in Sweden, scores would be more useful
      if they could also predict an easy airway, so that the correct category of
      anesthesia personnel can be allocated. Therefore, we evaluated whether scoring
      systems commonly used to predict difficult airways could also predict easy
      endotracheal intubation. DESIGN: This prospective observational study included
      patients who were scheduled for general anesthesia and required endotracheal
      intubation. METHODS: Airways were evaluated preoperatively by two independent
      variables, namely Mallampati classification and thyromental distance. After
      anesthesia induction, the Cormack and Lehane grade was assessed. FINDING:
      Mallampati scores yielded the highest specificity in predicting easy intubation,
      and Cormack and Lehane grades yielded the highest positive predictive value for
      predicting easy intubation. CONCLUSIONS: Mallampati classification is an
      appropriate screening test for predicting easy intubation.

PMID- 25062574
TI  - Evaluation and control of waste anesthetic gases in the postanesthesia care unit.
AB  - BACKGROUND: Few studies have addressed waste anesthetic gases (WAGs) in the
      postanesthesia care unit (PACU) related to exhaled sevoflurane and nitrous oxide.
      PURPOSE: To evaluate the effectiveness of a new scavenging system to control WAGs
      in the PACU. DESIGN: Comparative and descriptive study. METHODS: This pilot study
      compared exposure to WAGs with and without a scavenging system using infrared
      technology to visualize and quantify exposure to these gases in the PACU.
      FINDING: The results showed a significant reduction (P < .05) in both nitrous
      oxide and sevoflurane at both six inches and three feet from the patient's
      breathing zone, as well as in the work area of the perianesthesia nurses in the
      PACU. CONCLUSIONS: WAG exposure may be more easily managed through the use of
      this new scavenging system to better control occupational exposures to these
      gases among PACU personnel.

PMID- 25062575
TI  - Understanding sickle cell anemia in the perianesthesia arena.

PMID- 25062576
TI  - Preventing postsurgical venous thromboembolism.

PMID- 25062577
TI  - Every nurse a leader.

PMID- 25062578
TI  - Building respect.

PMID- 25062579
TI  - Antidepressant pharmacology and perioperative implications.

PMID- 25062580
TI  - Environmental hazards: waste anesthesia gases.

PMID- 25062581
TI  - Embracing all types of clinical inquiry: guest editorial.

PMID- 25062582
TI  - Effect of complete denture occlusal schemes on masticatory performance and
      maximum occlusal force.
AB  - STATEMENT OF PURPOSE: Masticatory performance and maximum occlusal force may be
      different, depending on the occlusal schemes of the complete dentures used.
      PURPOSE: The purpose of this study was to evaluate the effect of 2 complete
      denture occlusal schemes on masticatory performance and maximum occlusal force.
      MATERIAL AND METHODS: Two complete denture occlusal schemes, bilateral balanced
      occlusion and neutrocentric occlusion, were delivered to 10 participants who were
      completely edentulous (6 men and 4 women; mean age, 67.3 years). Masticatory
      performance was evaluated with the multiple sieve method and maximum occlusal
      force with pressure-sensitive films. The 2 occlusal schemes were interchanged on
      the participants' denture bases. Two-way repeated-measures ANOVA was used to
      examine the differences between the occlusal schemes and chewing strokes and
      their interactions. The paired t test was used to compare the maximum occlusal
      force of the 2 occlusal schemes (alpha=.05). RESULTS: No difference was found in
      masticatory performance (P=.07) or maximum occlusal force (P=.31) between the
      occlusal schemes. For both schemes, a significant difference was found in
      masticatory performance (P<.001) with increased numbers of chewing strokes.
      CONCLUSIONS: Complete dentures with bilateral balanced occlusion and
      neutrocentric occlusion found no significant differences in masticatory
      performance and maximum occlusal force. However, more chewing strokes resulted in
      better masticatory performance.

PMID- 25062583
TI  - Biomechanical evaluation of screw- and cement-retained implant-supported
      prostheses: a nonlinear finite element analysis.
AB  - STATEMENT OF PROBLEM: The mechanical stability of the prosthetic components in
      the implant-prosthesis complex is essential to the long-term success of the
      restorations. However, little is known about the differences in the biomechanical
      behavior of screw- and cement-retained prostheses. PURPOSE: The purpose of this
      study was to compare the preload maintenance, stresses, and displacements of
      prosthetic components of screw- and cement-retained implant-supported prostheses
      by using the finite element method in a nonlinear analysis. MATERIAL AND METHODS:
      Two 3-dimensional models were constructed: implant-supported fixed partial
      prostheses with 3 elements retained either by screws (SFP) or cement (CFP). After
      the simulation of screw tightening, the preload was calculated for both
      prostheses. Then vertical and oblique loads (100 N) were applied on the models.
      The preload was identified, the maximum von Mises equivalent stresses (SEQV) were
      obtained on the screws, and the displacement among the abutment, the implant, and
      screw was identified by observing the penetration and gap in the contact
      interfaces. RESULTS: Under vertical load, there was a higher decrease in the
      preload and in the SEQV on the screw in the SFP. Under oblique load, the SEQV was
      24% higher on the screw of the SFP. In the displacement analysis under vertical
      load, penetration was concentrated in the threads of the screw in the SFP and
      between the abutment and implant in the CFP. The gap was 118% greater for the SFP
      and was concentrated on the abutment extension. Under oblique load, the
      displacement pattern was similar for both prostheses, but with values 66% higher
      for penetration and 96% higher for gap for the SFP. CONCLUSIONS: The SFP showed a
      higher biomechanical risk of failure than the CFP.

PMID- 25062584
TI  - Timing and recovery of postweaning exposure to diethylstilbestrol on early
      pregnancy in CD-1 mice.
AB  - Exposure timing could play an important role in the effects of estrogenic
      endocrine disrupting chemicals (EEDCs) on early pregnancy. This study examined
      the sensitivity of different exposure periods from weaning to gestation day 4.5
      (D4.5) to 50ppb diethylstilbestrol (DES, a test EEDC) diet on embryo implantation
      and potential recovery upon temporary cessation of DES exposure in CD-1 mice.
      Peripubertal (3-5 weeks old) DES exposure reduced the numbers of corpora lutea
      and implantation sites. Postpubertal (5-7 weeks old) DES exposure did not have
      significant effects on early pregnancy. Postmating (D0.5-D4.5) DES exposure
      affected postovulation events leading to impaired embryo implantation. A 5-day
      premating rest from 5-week DES exposure (3-8 weeks old) resulted in recovery of
      early pregnancy rate. These data demonstrate that peripubertal and postmating
      periods are sensitive windows to endocrine disruption of early pregnancy and
      temporary cessation of exposure could partially alleviate adverse effects of DES
      on early pregnancy. 

PMID- 25062585
TI  - Metabotropic glutamate receptors inhibit GABA release in rat histamine neurons.
AB  - The modulation of GABAergic transmission by metabotropic glutamate (mGlu)
      receptors was examined in histaminergic neurons using a conventional whole-cell
      patch clamp technique. DHPG, a selective group I mGlu receptor agonist, had no
      effect on GABAergic inhibitory postsynaptic currents (IPSCs). However, DCG-IV
      (1MUM) and L-AP4 (1MUM), selective group II or III mGlu receptor agonists,
      respectively, decreased the amplitude of GABAergic IPSCs and simultaneously
      increased the paired-pulse ratio. The inhibitory effect of DCG-IV was completely
      blocked by 200nM LY341495, a group II and III mGlu receptor antagonist, and the
      inhibitory effect of L-AP4 was completely blocked by 10MUM LY341495. These
      results suggest that multiple mGlu receptors are involved in regulating the
      excitability of histaminergic neurons. 

PMID- 25062586
TI  - cAMP, cGMP, cCMP and cUMP concentrations across the tree of life: High cCMP and
      cUMP levels in astrocytes.
AB  - Adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic
      monophosphate (cGMP) are well-established second messengers, whereas the
      physiological role of the cyclic pyrimidine nucleotides cytidine 3',5'-cyclic
      monophosphate (cCMP) and uridine 3',5'-cyclic monophosphate (cUMP) is poorly
      understood. Certain mammalian nucleotidyl cyclases (NCs) and bacterial NC toxins
      can generate cCMP and cUMP. Human HEK293 cells and rat B103 neuroblastoma cells
      are of neuronal origin and possess high basal concentrations of cCMP and cUMP
      that can be attributed to soluble adenylyl cyclase activity. These data prompted
      us to conduct a systematic analysis of basal nucleoside 3',5'-cyclic
      monophosphate (cNMP) concentrations across the tree of life. cCMP and cUMP were
      identified in many mammalian cell lines and primary cells. cNMP patterns varied
      broadly among cells, and in several systems, cCMP and cUMP concentrations were
      quite high. Prokaryotes, fungi, amoeba and invertebrates lacked cCMP and cUMP,
      whereas cAMP was found across the tree of life. High cCMP and cUMP concentrations
      were found in astrocytes. The distinct cNMP patterns support specific second
      messenger roles of cCMP and cUMP, specifically in astrocytes. 

PMID- 25062587
TI  - Here/in this issue and there/abstract thinking: depression in youths: from LMIC
      to rTMS.

PMID- 25062588
TI  - Commercial sexual exploitation of children and the role of the child
      psychiatrist.

PMID- 25062589
TI  - Meta-analysis supports efficacy of behavioral interventions for attention
      deficit/hyperactivity disorder-related problems.

PMID- 25062590
TI  - Adolescents are like adults (sort of): psychosocial interventions for adolescents
      with or vulnerable to schizophrenia.

PMID- 25062591
TI  - Behavioral interventions in attention-deficit/hyperactivity disorder: a meta
      analysis of randomized controlled trials across multiple outcome domains.
AB  - OBJECTIVE: Behavioral interventions are recommended as attention
      deficit/hyperactivity disorder (ADHD) treatments. However, a recent meta-analysis
      found no effects on core ADHD symptoms when raters were probably blind to
      treatment allocation. The present analysis is extended to a broader range of
      child and parent outcomes. METHOD: A systematic search in PubMed, Ovid, Web of
      Knowledge, ERIC, and CINAHAL databases (up to February 5, 2013) identified
      published randomized controlled trials measuring a range of patient and parent
      outcomes for children and adolescents diagnosed with ADHD (or who met validated
      cutoffs on rating scales). RESULTS: Thirty-two of 2,057 nonduplicate screened
      records were analyzed. For assessments made by individuals closest to the
      treatment setting (usually unblinded), there were significant improvements in
      parenting quality (standardized mean difference [SMD] for positive parenting
      0.68; SMD for negative parenting 0.57), parenting self-concept (SMD 0.37), and
      child ADHD (SMD 0.35), conduct problems (SMD 0.26), social skills (SMD 0.47), and
      academic performance (SMD 0.28). With probably blinded assessments, significant
      effects persisted for parenting (SMD for positive parenting 0.63; SMD for
      negative parenting 0.43) and conduct problems (SMD 0.31). CONCLUSION: In contrast
      to the lack of blinded evidence of ADHD symptom decrease, behavioral
      interventions have positive effects on a range of other outcomes when used with
      patients with ADHD. There is blinded evidence that they improve parenting and
      decrease childhood conduct problems. These effects also may feed through into a
      more positive parenting self-concept but not improved parent mental well-being.

PMID- 25062593
TI  - Cognitive remediation therapy in adolescents with early-onset schizophrenia: a
      randomized controlled trial.
AB  - OBJECTIVE: Cognitive impairment is an enduring and functionally relevant feature
      of early-onset schizophrenia (EOS). Cognitive remediation therapy (CRT) improves
      cognition and functional outcome in adults with schizophrenia, although data in
      adolescents with EOS remain scarce. The purpose of this study is to examine the
      efficacy of CRT in improving cognition and functional outcomes in a sample of
      symptomatically stable but cognitively disabled adolescents with EOS. METHOD: We
      performed a randomized, controlled trial of individually delivered CRT plus
      treatment-as-usual compared with treatment-as-usual (TAU). Fifty adolescents with
      EOS were randomly assigned to receive CRT (n = 25) or TAU (n = 25) and were
      included in an intention-to-treat analysis. Clinical symptoms and cognitive and
      functional performance were assessed before and after treatment in both groups
      and after 3 months in the CRT group. Cognitive domains were defined according to
      the Measurement and Treatment Research to Improve Cognition in Schizophrenia
      (MATRICS) consensus battery and averaged in a global cognitive composite score.
      RESULTS: After CRT, significant improvements were found in verbal memory and
      executive functions, with medium-to-large effect sizes (ES). The derived
      cognitive composite score showed an improvement after the treatment, with a large
      ES. This change was reliable in more than two-thirds of the treated patients.
      Medium-sized ES were found for improvements after CRT in daily living and
      adaptive functioning, whereas large ES were observed for improvements in family
      burden. With the exception of functional gains, these changes were maintained
      after 3 months. CONCLUSION: CRT appears to be a useful intervention strategy for
      adolescents with EOS. Cognitive improvements can be achieved through CRT,
      although further research is warranted to determine the durability of functional
      gains. Clinical trial registration information-Cognitive Remediation Therapy
      (CRT) in Adolescents With EOS; www.clinicaltrials.gov; NCT01701609.

PMID- 25062592
TI  - Family-focused treatment for adolescents and young adults at high risk for
      psychosis: results of a randomized trial.
AB  - OBJECTIVE: Longitudinal studies have begun to clarify the phenotypic
      characteristics of adolescents and young adults at clinical high risk for
      psychosis. This 8-site randomized trial examined whether a 6-month program of
      family psychoeducation was effective in reducing the severity of attenuated
      positive and negative psychotic symptoms and enhancing functioning among
      individuals at high risk. METHOD: Adolescents and young adults (mean age 17.4 +/-
      4.1 years) with attenuated positive psychotic symptoms, brief and intermittent
      psychosis, or genetic risk with functional deterioration were randomly assigned
      to 18 sessions of family-focused therapy for individuals at clinical high risk
      (FFT-CHR) in 6 months or 3 sessions of family psychoeducation (enhanced care
      [EC]). FFT-CHR included psychoeducation about early signs of psychosis, stress
      management, communication training, and problem-solving skills training, whereas
      EC focused on symptom prevention. Independent evaluators assessed participants at
      baseline and 6 months on positive and negative symptoms and social-role
      functioning. RESULTS: Of 129 participants, 102 (79.1%) were followed up at 6
      months. Participants in FFT-CHR showed greater improvements in attenuated
      positive symptoms over 6 months than participants in EC (F1,97 = 5.49, p = .02).
      Negative symptoms improved independently of psychosocial treatments. Changes in
      psychosocial functioning depended on age: participants more than 19 years of age
      showed more role improvement in FFT-CHR, whereas participants between 16 and 19
      years of age showed more role improvement in EC. The results were independent of
      concurrent pharmacotherapy. CONCLUSION: Interventions that focus on improving
      family relationships may have prophylactic efficacy in individuals at high risk
      for psychosis. Future studies should examine the specificity of effects of family
      intervention compared to individual therapy of the same duration and frequency.
      Clinical trial registration information-Prevention Trial of Family Focused
      Treatment in Youth at Risk for Psychosis; http://clinicaltrials.gov/;
      NCT01907282.

PMID- 25062594
TI  - Co-rumination and co-problem solving in the daily lives of adolescents with major
      depressive disorder.
AB  - OBJECTIVE: This study examines differences in the prevalence and nature of co
      rumination during real-world social interactions with peers and parents among
      adolescents with major depressive disorder (MDD) compared to healthy controls.
      METHOD: A total of 60 youth (29 with current MDD and 31 controls without
      psychopathology) completed a self-report measure of co-rumination and a 3-week
      ecological momentary assessment (EMA) protocol that measured the nature of face
      to-face social interactions with peers and parents after a negative event in the
      adolescents' daily lives. Specifically, EMA was used to assess rates of problem
      talk, including both co-rumination and co-problem solving. Group differences in
      self-report and EMA measures were examined. RESULTS: Adolescents with MDD
      reported co-ruminating more often than adolescents with no Axis 1 disorders
      during daily interactions with both parents (Cohen's d = 0.78) and peers (d =
      1.14), and also reported more co-rumination via questionnaire (d = 0.58).
      Adolescents with MDD engaged in co-problem solving with peers less often than did
      healthy controls (d = 0.78), but no group differences were found for rates of co
      problem solving with parents. CONCLUSIONS: Results are consistent with previous
      research linking co-rumination and depression in adolescence and extend these
      self-report-based findings to assessment in an ecologically valid context.
      Importantly, the results support that MDD youth tend to co-ruminate more and to
      problem-solve less with peers in their daily lives compared to healthy youth, and
      that co-rumination also extends to parental relationships. Interventions focused
      on decreasing co-rumination with peers and parents and improving problem-solving
      skills with peers may be helpful for preventing and treating adolescent
      depression.

PMID- 25062596
TI  - Crime and psychiatric disorders among youth in the US population: an analysis of
      the National Comorbidity Survey-Adolescent Supplement.
AB  - OBJECTIVE: Current knowledge regarding psychiatric disorders and crime in youth
      is limited to juvenile justice and community samples. This study examined
      relationships between psychiatric disorders and self-reported crime involvement
      in a sample of youth representative of the US population. METHOD: The National
      Comorbidity Survey-Adolescent Supplement (N = 10,123; ages 13-17 years; 2001
      2004) was used to examine the relationship between lifetime DSM-IV-based
      diagnoses, reported crime (property, violent, other), and arrest history.
      Logistic regression compared the odds of reported crime involvement with specific
      psychiatric disorders to those without any diagnoses, and examined the odds of
      crime by psychiatric comorbidity. RESULTS: Prevalence of crime was 18.4%. Youth
      with lifetime psychiatric disorders, compared to no disorders, had significantly
      greater odds of crime, including violent crime. For violent crime resulting in
      arrest, conduct disorder (CD) (odds ratio OR = 57.5; 95% CI = 30.4, 108.8),
      alcohol use disorders (OR = 19.5; 95% CI = 8.8, 43.2), and drug use disorders (OR
      = 16.1; 95% CI = 9.3, 27.7) had the greatest odds with similar findings for
      violent crime with no arrest. Psychiatric comorbidity increased the odds of
      crime. Youth with 3 or more diagnoses (16.0% of population) accounted for 54.1%
      of those reporting arrest for violent crime. Youth with at least 1 diagnosis
      committed 85.8% of crime, which was reduced to 67.9% by removing individuals with
      CD. Importantly, 88.2% of youth with mental illness reported never having
      committed any crime. CONCLUSION: Our findings highlight the importance of
      improving access to mental health services for youthful offenders in community
      settings, given the substantial associations found between mental illness and
      crime in this nationally representative epidemiological sample.

PMID- 25062595
TI  - Parent training: equivalent improvement in externalizing behavior for children
      with and without familial risk.
AB  - OBJECTIVE: The Incredible Years Series intervention has demonstrated efficacy for
      decreasing conduct disorder (CD) symptomatology in clinically affected youth in
      multiple randomized controlled trials. Because children with family psychiatric
      histories of antisocial behavior are at markedly increased risk for enduring
      symptoms of antisocial behavior (compared with their counterparts with a negative
      family history), the authors examined whether intervention effects across studies
      would prevail in that subgroup or would be relatively restricted to children
      without genetic risk. METHOD: A reanalysis was conducted of 5 randomized
      controlled trials of Incredible Years involving 280 clinically affected children
      3 to 8 years of age for whom a family psychiatric history of externalizing
      behavior in first- and second-degree relatives was ascertained from at least 1
      parent. RESULTS: Incredible Years equally benefitted children with CD with and
      without family psychiatric histories of externalizing behavior. Family
      psychiatric history of externalizing behavior and parental depressive
      symptomatology predicted greater severity of CD symptomatology at baseline.
      CONCLUSION: The beneficial effects of IY are evident in children with CD,
      irrespective of whether their conditions are more or less attributable to
      inherited susceptibility to enduring antisocial syndromes. A next phase of
      research should address whether earlier implementation of group-based education
      for parents of young children at increased familial risk for antisocial behavior
      syndromes-before the development of disruptive patterns of behavior-would result
      in even more pronounced effects and thereby constitute a cost-effective,
      targeted, preventive intervention for CD.

PMID- 25062599
TI  - College and its vagaries.

PMID- 25062597
TI  - White matter correlates of adolescent depression: structural evidence for
      frontolimbic disconnectivity.
AB  - OBJECTIVE: Despite the significant prevalence of adolescent depression, little is
      known about the neuroanatomical basis of this disorder. Functional dysregulation
      in frontolimbic circuitry has been suggested as a key neural correlate of adult
      and adolescent depression impeding emotional regulation. However, less is known
      about whether this dysregulation is overlaid on impaired white matter
      microstructure. Guided by neuroimaging findings, we test the a priori hypotheses
      that adolescent depression is associated with alterations in white matter
      microstructure in the uncinate fasciculus (UF) and cingulum bundles. METHOD:
      Diffusion tensor magnetic resonance imaging (DTI) data were obtained on 52
      unmedicated adolescents with major depressive disorder (MDD) and 42 matched
      controls. We calculated fractional anisotropy (FA), radial diffusivity (RD), and
      axial diffusivity (AD) for bilateral UF and cingulum. We also completed a
      voxelwise comparison of participants with depression and control participants
      using tract-based spatial statistics (TBSS). RESULTS: Adolescents with depression
      had significantly lower FA and higher RD in bilateral UF; no significant
      differences were observed in cingulum. TBSS results additionally revealed lower
      FA values in the white matter associated with the limbic-cortical-striatal
      thalamic circuit, corpus callosum, and anterior and superior corona radiata.
      CONCLUSION: Unmedicated adolescent depression is associated with reduced
      fractional anisotropy in emotion regulatory networks, which may underlie the
      functional differences in frontolimbic circuitry characterizing depressive
      disorder. Given the relatively recent onset of depression in our sample, our
      findings in the context of the current literature provide preliminary evidence
      that reduced fractional anisotropy in the UF could be a predisposing risk factor
      for depression.

PMID- 25062600
TI  - Retrograde lag screw placement in anterior acetabular column with regard to the
      anterior pelvic plane and midsagittal plane -- virtual mapping of 260 three
      dimensional hemipelvises for quantitative anatomic analysis.
AB  - Percutaneous screw placement can be used for minimally invasive treatment of none
      or minimally displaced fractures of the anterior column. The complex pelvic
      geometry can pose a major challenge even for experienced surgeons. The present
      study examined the preformed bone stock of the anterior column in 260
      hemipelvises (130 male and 130 female). Screws were virtually implanted using
      iPlan((r)) CMF (BrainLAB AG, Feldkirchen, Germany); the maximal implant length
      and the maximal implant diameter were assessed. The study showed, that 6.5mm can
      generally be used in men; in women however individual planning is essential in
      regard to the maximal implant diameter since we found that in 15.4% of women,
      screws with a diameter less than 6.5mm were necessary. The virtual analysis of
      the preformed bone stock corridor of the anterior column showed two constrictions
      of crucial clinical importance. These can be found after 18% and 55% (men)
      respectively 16% and 55% (women) measured from the entry point along the axis of
      the implant. The entry point of the retrograde anterior column screw in our
      collective was located lateral of tuberculum pubicum at the level of the superior
      medial margin of foramen obturatum. In female patients, the entry point was
      located significantly more lateral of symphysis and closer to the cranial margin
      of ramus superior ossis pubis. The mean angle between the screw trajectory and
      the anterior pelvic plane in sagittal section was 31.6 +/- 5.5 degrees , the mean
      angle between the screw trajectory and the midsagittal plane in axial section was
      55.9 +/- 4.6 degrees  and the mean angle between the screw trajectory and the
      midsagittal plane in coronal section was 42.1 +/- 3.9 degrees  with no
      significant deviation between both sexes. The individual angles formed by the
      screw trajectory and the anterior pelvic and midsagittal plane are independent
      from anthropometric parameters sex, age, body length and weight. Therefore, they
      can be used for orientation in lag screw placement keeping in mind that the entry
      point differs in both sexes.

PMID- 25062601
TI  - What is the yield of routine chest radiography following tube thoracostomy for
      trauma?
AB  - INTRODUCTION: Routine chest radiography (CXR) following tube thoracostomy (TT) is
      a standard practice in most trauma centres worldwide. Evidence supporting this
      routine practice is lacking and the actual yield is unknown. MATERIALS AND
      METHODS: We performed a retrospective review of 1042 patients over a 4-year
      period who had a routine post-insertion CXR performed in accordance with current
      ATLS(r) recommendations. RESULTS: A total 1042 TTs were performed on 1004
      patients. Ninety-one per cent of patients (913/1004) were males, and the median
      age for all patients was 24 years. Seventy-five per cent of all injuries
      (756/1004) were from penetrating trauma, and the remaining 25% (248/1004) were
      from blunt. The initial pathologies requiring TT were: haemopneumothorax: 34%
      (339/1042), haemothroax: 31% (314/1042), simple pneumothorax: 25% (256/1042),
      tension pneumothorax: 8% (77/1042) and open pneumothorax: 5% (54/1042). One
      hundred and three patients had TTs performed on clinical grounds alone without a
      pre-insertion CXR [Group A]. One hundred and ninety-one patients had a pre
      insertion CXR but had persistent clinical concerns following insertion [Group B].
      Seven hundred and ten patients had pre-insertion CXR but no clinical concerns
      following insertion [Group C]. Overall, 15% (152/1004) [9 from Group A, 111 from
      Group B and 32 from Group C] of all patients had their clinical management
      influenced as a direct result of the post-insertion CXR. CONCLUSIONS: Despite the
      widely accepted practice of routine CXR following tube thoracostomy, the yield is
      relatively low. In many cases, good clinical examination post tube insertion will
      provide warnings as to whether problems are likely to result. However, in the
      more rural setting, and in resource challenged environments, there is a
      relatively high yield from the CXR, which alters management. Further prospective
      studies are needed to establish or refute the role of the existing ATLS(r)
      guidelines in these specific environments.

PMID- 25062602
TI  - Health outcomes of delayed union and nonunion of femoral and tibial shaft
      fractures.
AB  - INTRODUCTION: Knowledge about the functional consequences of lower limb long bone
      fractures is helpful to inform patients, clinicians and employers about their
      recovery process and prognosis. This study aims to describe the epidemiology and
      health outcomes of femoral and tibial shaft fractures treated at two level I
      trauma centres, by comparing the differences between patients with delayed union
      or nonunion and patients with union. PATIENTS AND METHODS: An analysis of
      registry data over two years, supplemented with medical record review, was
      conducted. Fracture healing was retrospectively assessed by clinical and
      radiological evidence of union, and the need for surgical intervention. SF-12
      scores, and work and pain status were prospectively recorded at six and twelve
      months post injury. RESULTS: 285 fractures progressed to union and 138 fractures
      developed delayed union or nonunion. There was a significant difference between
      the two cohorts with regards to the mechanism of injury, association with multi
      trauma, open fractures, grade of Gustilo classification, patient fund source,
      smoking status and presence of comorbidities. The SF-12 physical component score
      was less than 50 at both six and twelve months with improvement in the union
      group, but not in the delayed union or nonunion group. 72% of patients with union
      had returned to work at one year, but 54% continued to have pain. The difference
      compared to patients with delayed union or nonunion was significant. DISCUSSION:
      Even patients whose fractures unite in the expectant time-frame will have
      residual physical disability. Patients with delayed union or nonunion have still
      poorer outcomes, including ongoing problems with returning to work and pain. It
      is important to educate patients about their injury so that they have realistic
      expectations. This is particularly relevant given that the patients most likely
      to sustain femoral or tibial shaft fractures are working-age healthy adults, and
      up to a third of fractures may develop delayed union or nonunion. CONCLUSION:
      Despite modern treatment, the patient-reported outcomes of lower limb long bone
      shaft fractures do not return to normal at one year. Patients with delayed union
      or nonunion can expect poorer outcomes.

PMID- 25062603
TI  - Wide-field fundus autofluorescence imaging to evaluate retinal function in
      patients with retinitis pigmentosa.
AB  - PURPOSE: To study the correlation between the visual fields (VF) and wide-field
      fundus autofluorescence (FAF) in patients with retinitis pigmentosa (RP). DESIGN:
      Retrospective, observational, consecutive case series. METHODS: Twenty-four eyes
      of 12 patients diagnosed with RP were enrolled. The VFs measured by Goldmann
      perimetry and wide-field FAF images were compared for each eye. The relationship
      between the areas of hypoautofluorescence on the wide-field FAF images and
      scotoma on Goldmann perimetry were evaluated. The VF and FAF images in the
      central 60 degrees were trimmed and superimposed to calculate the percentage
      agreement between the hypoautofluorescence and the scotomas and between the
      isoautofluorescence and hyperautofluorescence and the remaining VFs. RESULTS: The
      areas of hypoautofluorescence on the FAF images were correlated significantly (R
      = 0.86, P < .001) with the areas of the VF defects on Goldmann perimetry. The
      mean percentage agreement between the hypoautofluorescence and the scotomas was
      91.0% +/- 7.7% and that of the isoautofluorescence and hyperautofluorescence with
      the remaining VFs was 84.5% +/- 7.4%. The areas of geographic
      hypoautofluorescence with or without hyperautofluorescent bands reflected the VF
      defects, while nummular or mottled hypoautofluorescence without VF defects was
      seen in 7 eyes. CONCLUSIONS: These results suggested that wide-field FAF imaging
      is useful to evaluate the remaining retinal function in patients with RP.
      Abnormal fundus autofluorescence precedes loss of retinal function and is helpful
      for monitoring disease progression.

PMID- 25062598
TI  - Copy number variation in obsessive-compulsive disorder and tourette syndrome: a
      cross-disorder study.
AB  - OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are
      heritable neurodevelopmental disorders with a partially shared genetic etiology.
      This study represents the first genome-wide investigation of large (>500 kb),
      rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV
      analysis in TS to date. METHOD: The primary analyses used a cross-disorder design
      for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and
      1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios.
      RESULTS: Although no global CNV burden was detected in the cross-disorder
      analysis or in secondary, disease-specific analyses, there was a 3.3-fold
      increased burden of large deletions previously associated with other
      neurodevelopmental disorders (p = .09). Half of these neurodevelopmental
      deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0
      control deletions, p = .08 in the current study, p = .025 compared to published
      controls). Three 16p13.11 deletions were confirmed de novo, providing further
      support for the etiological significance of this region. The overall OCD de novo
      rate was 1.4%, which is intermediate between published rates in controls (0.7%)
      and in individuals with autism or schizophrenia (2-4%). CONCLUSION: Several
      converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker
      evidence for a role in TS. The trend toward increased overall neurodevelopmental
      CNV burden in TS and OCD suggests that deletions previously associated with other
      neurodevelopmental disorders may also contribute to these phenotypes.

PMID- 25062605
TI  - Changes in voluntary quadriceps activation predict changes in muscle strength and
      gait biomechanics following knee joint effusion.
AB  - BACKGROUND: It has been hypothesized that arthrogenic muscle inhibition is
      responsible for altering physical function following knee injury. The association
      between the onset of arthrogenic muscle inhibition, measured using voluntary
      quadriceps activation, and changes in muscle strength and gait biomechanics are
      unknown. METHODS: Outcomes were collected before and following a 60 ml
      experimental knee effusion in eighteen healthy participants. Voluntary quadriceps
      activation was the predictor variable, while the criterion variable included,
      maximal voluntary isometric strength, peak knee flexion angle, peak internal knee
      extension moment, and peak vertical ground reaction forces during the first half
      of stance phase upon stair descent. Percent change scores (Delta) were imputed
      into linear regression equations to determine associations between predictor and
      criterion variables. FINDINGS: The variance in Delta voluntary quadriceps
      activation significantly predicted 87% the variance in the Delta strength
      (R(2)=0.87, P<0.001; Delta strength=-2.15+1.77Delta voluntary quadriceps
      activation) and 25% of the Delta vertical ground reaction force following
      effusion (R(2)=0.25, P=0.04; Delta vertical ground reaction force=-6.1+0.57 Delta
      voluntary quadriceps activation). After accounting for Delta knee flexion angle,
      Delta voluntary quadriceps activation predicted an additional 29% (Delta
      R(2)=0.29, P=0.007) of the variance in the Delta knee extension moment
      (R(2)=0.54, P=0.003, Delta knee extension moment=-10.79+0.74Delta knee flexion
      angle+1.64Delta voluntary quadriceps activation) following knee effusion.
      INTERPRETATION: Immediate quadriceps activation deficits following joint effusion
      result in immediate alterations in muscle strength, knee extensor moment and
      vertical ground reaction force during gait.

PMID- 25062606
TI  - Synthesis of mesoporous silica@Co-Al layered double hydroxide spheres: layer-by
      layer method and their effects on the flame retardancy of epoxy resins.
AB  - Hierarchical mesoporous silica@Co-Al layered double hydroxide (m-SiO2@Co-Al LDH)
      spheres were prepared through a layer-by-layer assembly process, in order to
      integrate their excellent physical and chemical functionalities. TEM results
      depicted that, due to the electrostatic potential difference between m-SiO2 and
      Co-Al LDH, the synthetic m-SiO2@Co-Al LDH hybrids exhibited that m-SiO2 spheres
      were packaged by the Co-Al LDH nanosheets. Subsequently, the m-SiO2@Co-Al LDH
      spheres were incorporated into epoxy resin (EP) to prepare specimens for
      investigation of their flame-retardant performance. Cone results indicated that m
      SiO2@Co-Al LDH incorporated obviously improved fire retardant of EP. A plausible
      mechanism of fire retardant was hypothesized based on the analyses of thermal
      conductivity, char residues, and pyrolysis fragments. Labyrinth effect of m-SiO2
      and formation of graphitized carbon char catalyzed by Co-Al LDH play pivotal
      roles in the flame retardance enhancement. 

PMID- 25062604
TI  - Changes in expression of Class 3 Semaphorins and their receptors during
      development of the rat retina and superior colliculus.
AB  - BACKGROUND: Members of the Semaphorin 3 family (Sema3s) influence the development
      of the central nervous system, and some are implicated in regulating aspects of
      visual system development. However, we lack information about the timing of
      expression of the Sema3s with respect to different developmental epochs in the
      mammalian visual system. In this time-course study in the rat, we document for
      the first time changes in the expression of RNAs for the majority of Class 3
      Semaphorins (Sema3s) and their receptor components during the development of the
      rat retina and superior colliculus (SC). RESULTS: During retinal development,
      transcript levels changed for all of the Sema3s examined, as well as Nrp2,
      Plxna2, Plxna3, and Plxna4a. In the SC there were also changes in transcript
      levels for all Sema3s tested, as well as Nrp1, Nrp2, Plxna1, Plxna2, Plxna3, and
      Plxna4a. These changes correlate with well-established epochs, and our data
      suggest that the Sema3s could influence retinal ganglion cell (RGC) apoptosis,
      patterning and connectivity in the maturing retina and SC, and perhaps guidance
      of RGC and cortical axons in the SC. Functionally we found that SEMA3A, SEMA3C,
      SEMA3E, and SEMA3F proteins collapsed purified postnatal day 1 RGC growth cones
      in vitro. Significantly this is a developmental stage when RGCs are growing into
      and within the SC and are exposed to Sema3 ligands. CONCLUSION: These new data
      describing the overall temporal regulation of Sema3 expression in the rat retina
      and SC provide a platform for further work characterising the functional impact
      of these proteins on the development and maturation of mammalian visual pathways.

PMID- 25062607
TI  - Mechanosensors in integrin signaling: the emerging role of p130Cas.
AB  - Physicochemical interactions between the cell and its environment are crucial for
      morphogenesis, tissue homeostasis, remodeling and pathogenesis. Cells form
      specialized structures like focal adhesions and podosomes that are responsible
      for bi-directional information exchange between the cell and its surroundings.
      Besides their role in the transmission of regulatory signals, these structures
      are also involved in mechanosensing and mechanotransduction. In the past few
      years, many research groups have been trying to elucidate the mechanisms and
      consequences of the mechanosensitivity of cells. In this review we discuss the
      role of the integrin pathway in cellular mechanosensing, focusing on primary
      mechanosensors, molecules that respond to mechanical stress by changing their
      conformation. We propose mechanisms by which p130Cas is involved in this process,
      and emphasize the importance of mechanosensing in cell physiology and the
      development of diseases. 

PMID- 25062609
TI  - Isolation and molecular identification of lactic acid bacteria and
      Bifidobacterium spp. from faeces of the blue-fronted Amazon parrot in Brazil.
AB  - In Brazil, the blue-fronted Amazon parrot (Amazona aestiva) is a common pet. The
      faecal microbiota of these birds include a wide variety of bacterial species, the
      majority of which belong to the Gram-positive lactic acid bacteria (LAB) clade.
      The aim of this study was to investigate differences in the diversity and
      abundance of LAB and Bifidobacterium spp. in the cloacae between wild and captive
      birds and to select, identify and characterise LAB for consideration as a parrot
      probiotic. Cloacal swabs were collected from 26 wild and 26 captive birds.
      Bacterial DNA was extracted, and the 16S rRNA genes were amplified. The numbers
      of PCR-positive Enterococcus, Pediococcus, and Lactobacillus species isolated
      from wild and captive birds were significantly different (P<0.05). Enterococcus
      was the most frequently isolated genus, followed by Pediococcus, Lactobacillus,
      Lactococcus and Bifidobacterium. Enterococcus faecium, Pediococcus pentosaceus,
      Lactococcus lactis, Lactobacillus coryniformis, Lactobacillus sanfranciscensis
      and Bifidobacterium bifidum were the most frequently isolated species from all
      birds. This study increases our understanding of the faecal microbiota, and may
      help to improve the nutrition and habitat management of captive and wild parrots.
      The bacterial population identified in the faecal microbiota of clinically
      healthy wild and captive parrots can serve as a database to analyse variations in
      the gut microbiota of pathogen-infected parrots and to develop probiotics
      specific to these genera. 

PMID- 25062610
TI  - Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain
      and glucose intolerance in diet-induced obese mice.
AB  - Alterations of the gut microbiota and mucosal barrier are linked with metabolic
      diseases. Our aim was to investigate the potential benefit of the potential
      probiotic Bifidobacterium animalis ssp. lactis 420 in reducing high-fat diet
      induced body weight gain and diabetes in mice. In the obesity model, C57Bl/6J
      mice were fed a high-fat diet (60 energy %) for 12 weeks, and gavaged daily with
      B. lactis 420 (109 cfu) or vehicle. In the diabetes model, mice were fed a high
      fat, ketogenic diet (72 energy % fat) for 4 weeks, with a 6-week subsequent
      treatment with B. lactis 420 (108-1010 cfu/day) or vehicle, after which they were
      analysed for body composition. We also analysed glucose tolerance, plasma
      lipopolysaccharide and target tissue inflammation using only one of the B. lactis
      420 groups (109 cfu/day). Intestinal bacterial translocation and adhesion were
      analysed in a separate experiment using an Escherichia coli gavage. Body fat mass
      was increased in both obese (10.7 +/- 0.8 g (mean +/- standard error of mean) vs.
      1.86 +/- 0.21 g, P<0.001) and diabetic mice (3.01 +/- 0.4 g vs. 1.14 +/- 0.15 g,
      P<0.001) compared to healthy controls. Treatment with B. lactis 420 significantly
      decreased fat mass in obese (7.83 +/- 0.67 g, P=0.007 compared to obese with
      vehicle) and diabetic mice (1.89 +/- 0.16 g, P=0.02 for highest dose). This was
      reflected as reduced weight gain and improved glucose tolerance. Furthermore, B.
      lactis 420 decreased plasma lipopolysaccharide levels (P<0.001), liver
      inflammation (P=0.04), and E. coli adhesion in the distal gut (P<0.05). In
      conclusion, B. lactis 420 reduces fat mass and glucose intolerance in both obese
      and diabetic mice. Reduced intestinal mucosal adherence and plasma
      lipopolysaccharide suggest a mechanism related to reduced translocation of gut
      microbes.

PMID- 25062608
TI  - Ephrin-mediated restriction of ERK1/2 activity delimits the number of pigment
      cells in the Ciona CNS.
AB  - Recent evidence suggests that ascidian pigment cells are related to neural crest
      derived melanocytes of vertebrates. Using live-imaging, we determine a revised
      cell lineage of the pigment cells in Ciona intestinalis embryos. The neural
      precursors undergo successive rounds of anterior-posterior (A-P) oriented cell
      divisions, starting at the blastula 64-cell stage. A previously unrecognized
      fourth A-P oriented cell division in the pigment cell lineage leads to the
      generation of the post-mitotic pigment cell precursors. We provide evidence that
      MEK/ERK signals are required for pigment cell specification until approximately
      30min after the final cell division has taken place. Following each of the four A
      P oriented cell divisions, ERK1/2 is differentially activated in the posterior
      sister cells, into which the pigment cell lineage segregates. Eph/ephrin signals
      are critical during the third A-P oriented cell division to spatially restrict
      ERK1/2 activation to the posterior daughter cell. Targeted inhibition of
      Eph/ephrin signals results in, at neurula stages, anterior expansion of both
      ERK1/2 activation and a pigment cell lineage marker and subsequently, at larval
      stages, supernumerary pigment cells. We discuss the implications of these
      findings with respect to the evolution of the vertebrate neural crest.

PMID- 25062611
TI  - Evaluation of Bacillus subtilis R0179 on gastrointestinal viability and general
      wellness: a randomised, double-blind, placebo-controlled trial in healthy adults.
AB  - A probiotic formulation of Enterococcus faecium R0026 and Bacillus subtilis R0179
      has been evaluated in previous clinical trials. However, B. subtilis R0179 has
      not been evaluated as a single probiotic strain or in combination with other
      strains at doses higher than 0.1*109 cfu. To establish oral dose-response
      tolerance and gastrointestinal (GI) viability of B. subtilis R0179, a randomised,
      double-blind, placebo-controlled trial in healthy adults (n=81; 18-50 years old)
      was conducted. Participants received B. subtilis R0179 at 0.1, 1.0 or 10*109
      cfu/capsule/day or placebo for four weeks. General wellness was assessed using a
      daily questionnaire evaluating GI, cephalic, ear-nose-throat, behavioural,
      emetic, and epidermal symptoms. GI symptoms were further evaluated using a weekly
      gastrointestinal symptom rating scale (GSRS). GI transit viability of B. subtilis
      R0179 was assessed by plating and microbiota analysis by 16S rRNA at baseline,
      week 4 of the intervention and washout. General wellness and GI function were not
      affected by oral consumption of B. subtilis R0179 at any dose. Daily
      questionnaire syndrome scores were not different from baseline and did not exceed
      a clinically significant score of 1. GSRS syndrome scores were not different from
      baseline and ranged from 1.1+/-0.1 to 1.9+/-0.2. Faecal viable counts of B.
      subtilis R0179 demonstrated a dose response: the placebo group (1.1+/-0.1 log10
      cfu/g) differed from 0.1*109 (4.6+/-0.1 log10 cfu/g), 1*109 (5.6+/-0.1 log10
      cfu/g) and 10*109 (6.4+/-0.1 log10 cfu/g) (P<0.0001). No significant changes in
      phyla were observed, but sequence reads binned to multiple operational taxonomic
      units matching closest to Ruminococci increased during probiotic supplementation.
      B. subtilis R0179 survives passage through the human GI tract and is well
      tolerated by healthy adults at intakes from 0.1 to 10*109 cfu/day. The trial has
      been registered at www.clinicaltrials.gov under NCT01802151. 

PMID- 25062612
TI  - Hypertensive patients in a general practice setting: comparative analysis between
      controlled and uncontrolled hypertension.
AB  - OBJECTIVE: To study the differences between controlled and uncontrolled
      hypertensive patients. METHODS: This was a cross-sectional observational study of
      the hypertensive population on the lists of three general practitioners in the
      district of Coimbra in central Portugal in 2013, with a margin of error of 6% and
      95% confidence interval in each sample, organized in ascending order of health
      care user numbers. Data were gathered electronically by the investigators after
      approval by the Regional Health Authority's ethics committee. RESULTS: A sample
      of 201 individuals was studied, of whom 104 (51.7%) were male and 86 (42.8%) were
      aged under 65 (p=0.127 for gender and age-group). Hypertension was controlled in
      130 (64.7%). We found significant differences in target organ damage, more
      frequent in those with controlled hypertension (33.1% vs. 19.7%, p=0.031), in
      hypertension control, better in those taking at least one anti-hypertensive drug
      at night (56.9% vs. 29.6%, p<0.001), and in prescription of non-steroidal anti
      inflammatory drugs, more frequent in those with uncontrolled hypertension (11.3%
      vs. 3.8%, p=0.043). CONCLUSION: Hypertension control is significantly associated
      with target organ damage, taking at least one anti-hypertensive drug at night and
      not taking non-steroidal anti-inflammatory drugs simultaneously.

PMID- 25062613
TI  - Relationship between parent demographic characteristics, perinatal and early
      childhood behaviors, and body mass index among preschool-age children.
AB  - Approximately 25% of US 2-to-5-year olds are overweight and ethnic minority
      groups are disproportionately affected. We explored the relationship between
      parent demographic characteristics, various perinatal/early childhood (EC)
      factors, and child body mass index (BMI) to determine possible contributors to
      these disparities. A preschool-based randomized controlled (N = 28 centers)
      obesity prevention intervention was conducted among multiethnic 2-to-5 year olds.
      Baseline assessment of demographic characteristics, various perinatal/EC factors,
      and child BMI were analyzed via generalized linear mixed models and logistic
      regression analysis. Foreign-born parents were almost 2.5 times as likely to have
      an obese child versus children of US-born parents (OR 2.43, 95% CI 1.53-3.87).
      Families who spoke Spanish only or a combination of Creole/English at home were
      over twice as likely to have an obese preschool child versus families who spoke
      English only at home. Parent place of birth and language spoken at home plays a
      significant role in early childhood obesity. Future early childhood healthy
      weight initiatives should incorporate strategies that take into account these
      particular parent characteristics.

PMID- 25062614
TI  - Trends and Disparities in Mortality Among Spanish-Born and Foreign-Born
      Populations Residing in Spain, 1999-2008.
AB  - Spain's immigrant population has increased 380% in the last decade, accounting
      for 13.1% of the total population. This fact has led her to become during 2009
      the eighth recipient country of international immigrants in the world. The aim of
      this article is to describe the evolution of mortality and the main causes of
      death among the Spanish-born and foreign-born populations residing in Spain
      between 1999 and 2008. Age-standardised mortality rates (ASRs), average age and
      comparative mortality ratios among foreign-born and Spanish-born populations
      residing in Spain were computed for every year and sub-period by sex, cause of
      death and place of birth as well as by the ASR percentage change. During 1999
      2008 the ASR showed a progressive decrease in the risk of death in the Spanish
      born population (-17.8% for men and -16.6% for women) as well as in the foreign
      born one (-45.9% for men and -35.7% for women). ASR also showed a progressive
      decrease for practically all the causes of death, in both populations. It has
      been observed that the risk of death due to neoplasms and respiratory diseases
      among immigrants is lower than that of their Spanish-born counterparts, but risk
      due to external causes is higher. Places of birth with the greater decreases are
      Northern Europe, Eastern Europe, Western Europe, Southern Europe, and Latin
      America and the Caribbean. The research shows the differences in the reduction of
      death risk between Spanish-born and immigrant inhabitants between 1999 and 2008.
      These results could contribute to the ability of central and local governments to
      create effective health policy. Further research is necessary to examine changes
      in mortality trends among immigrant populations as a consequence of the economic
      crisis and the reforms in the Spanish health system. Spanish data sources should
      incorporate into their records information that enables them to find out the
      immigrant duration of permanence and the possible impact of this on mortality
      indicators.

PMID- 25062616
TI  - Serum uric acid as a predictor of vascular complications in diabetes: an
      additional case for neuropathy.

PMID- 25062615
TI  - Effect of omega-3 fatty acids on haemostatic functions in urocortin-treated obese
      rats.
AB  - Urocortin 1 (UCN1) decreases food intake. We investigated the effects of UCN1 and
      omega-3 fatty acids (FA) on metabolic and coagulation parameters in high fat diet
      (HFD)-fed rats. Fifty male Sprague Dawley rats were divided into five groups;
      control, HFD, HFD with omega-3 FA, HFD with UCN1, and HFD with UCN1 and omega-3
      FA. Food intake, body weight (BW), body mass index (BMI), Lee index, glucose,
      insulin, HOMA-IR, triglycerides, cholesterol, low (LDL) and high (HDL) density
      lipoproteins, fibrinogen, plasminogen activator inhibitor 1 (PAI-1), fibrin
      degradation product (FDP), clotting time, bleeding time, prothrombin time (PT),
      activated partial thromboplastin time (aPTT), and platelet aggregation were
      measured. Food intake, BW, BMI, Lee index, glucose, insulin, HOMA-IR,
      triglycerides, cholesterol, LDL, fibrinogen, platelet aggregation, PAI-1, and FDP
      increased while bleeding and clotting times, PT, and aPTT decreased in HFD rats.
      UCN1 decreased food intake, BW, BMI, Lee index, bleeding and clotting times, PT,
      and aPTT and increased fibrinogen, PAI-1, FDP, and platelet aggregation in HFD
      rats. Omega-3 FA decreased food intake, BW, BMI, Lee index, platelet aggregation,
      glucose, insulin, HOMA-IR, triglycerides, and increased HDL and bleeding time in
      HFD rats. We concluded that UCN1 worsens the hypercoagulable state in HFD rats
      while omega-3 FA improve the insulin resistance and decrease the platelet
      aggregation in those rats. 

PMID- 25062617
TI  - Mathematical modeling for novel cancer drug discovery and development.
AB  - INTRODUCTION: Mathematical modeling enables: the in silico classification of
      cancers, the prediction of disease outcomes, optimization of therapy,
      identification of promising drug targets and prediction of resistance to
      anticancer drugs. In silico pre-screened drug targets can be validated by a small
      number of carefully selected experiments. AREAS COVERED: This review discusses
      the basics of mathematical modeling in cancer drug discovery and development. The
      topics include in silico discovery of novel molecular drug targets, optimization
      of immunotherapies, personalized medicine and guiding preclinical and clinical
      trials. Breast cancer has been used to demonstrate the applications of
      mathematical modeling in cancer diagnostics, the identification of high-risk
      population, cancer screening strategies, prediction of tumor growth and guiding
      cancer treatment. EXPERT OPINION: Mathematical models are the key components of
      the toolkit used in the fight against cancer. The combinatorial complexity of new
      drugs discovery is enormous, making systematic drug discovery, by
      experimentation, alone difficult if not impossible. The biggest challenges
      include seamless integration of growing data, information and knowledge, and
      making them available for a multiplicity of analyses. Mathematical models are
      essential for bringing cancer drug discovery into the era of Omics, Big Data and
      personalized medicine.

PMID- 25062618
TI  - The hematopoietic stem cell landscape.
AB  - Hematopoietic stem cells (HSCs) play critical roles in regulating normal blood
      cell development. Although initially these cells were mysterious and difficult to
      study in isolation, those obstacles have progressively been rolled away in just a
      few decades to reveal a heterogeneity of repopulating activity, cell
      proliferation, and energy metabolism within defined stem cell populations based
      on drug transporter and cell surface marker expression. A wide range of new
      technologies have driven innovative discovery of the regulators of HSCs and
      continued to move the field forward toward a full view of the landscape of single
      HSCs at the gene and protein levels. It is the goal of this overview chapter to
      summarize the array of techniques included in the third edition of Hematopoietic
      Stem Cell Protocols which will aid investigators in the field. 

PMID- 25062619
TI  - Investigating the interaction between hematopoietic stem cells and their niche
      during embryonic development: optimizing the isolation of fetal and newborn stem
      cells from liver, spleen, and bone marrow.
AB  - Hematopoietic stem cells (HSCs) are maintained in a particular microenvironment
      termed a "niche." Within the niche, a number of critical molecules and supportive
      cell types have been identified to play key roles in modulating adult HSC
      quiescence, proliferation, differentiation, and reconstitution. However, unlike
      in the adult bone marrow (BM), the components of stem cell niches, as well as
      their interactions with fetal HSC during different stages of embryonic
      development, are poorly understood. During embryogenesis, hematopoietic
      development migrates through multiple organs, each with different cellular and
      molecular components and hence each with a potentially unique HSC niche. As a
      consequence, isolating fetal HSC from each organ at the time of hematopoietic
      colonization is fundamental for assessing and understanding both HSC function and
      their interactions with specific microenvironments. Herein, we describe
      methodologies for harvesting cells as well as the purification of stem and
      progenitors from fetal and newborn liver, spleen, and BM at various developmental
      stages following the expansion of hematopoiesis in the fetal liver at E14.5. 

PMID- 25062620
TI  - Single-cell PCR profiling of gene expression in hematopoiesis.
AB  - Single-cell analysis of gene expression offers the possibility of exploring
      cellular and molecular heterogeneity in stem and developmental cell systems,
      including cancer, to infer routes of cellular specification and their respective
      gene regulatory modules. PCR-based technologies, although limited to the analysis
      of a predefined set of genes, afford a cost-effective balance of throughput and
      biological information and have become a method of choice in stem cell
      laboratories. Here we describe an experimental and analytical protocol based on
      the Fluidigm microfluidics platform for the simultaneous expression analysis of
      48 or 96 genes in multiples of 48 or 96 cells. We detail wet laboratory
      procedures and describe clustering, principal component analysis, correlation,
      and classification tools for the inference of cellular pathways and gene
      networks. 

PMID- 25062621
TI  - Hematopoietic stem and progenitor cell mobilization in mice.
AB  - Hematopoietic stem cell transplantation (HSCT) can be performed with
      hematopoietic stem and progenitor cells (HSPC) acquired directly from bone
      marrow, from umbilical cord blood or placental tissue, or from the peripheral
      blood after treatment of the donor with agents that enhance egress of HSPC into
      the circulation, a process known as "mobilization." Mobilized peripheral blood
      stem cells (PBSC) have become the predominate hematopoietic graft for HSCT,
      particularly for autologous transplants. Despite the success of PBSC transplant,
      many patients and donors do not achieve optimal levels of mobilization. Thus,
      accurate animal models and basic laboratory investigations are needed to further
      investigate the mechanisms that lead to PBSC mobilization and define improved or
      new mobilizing agents and/or strategies to enhance PBSC mobilization and
      transplant. This chapter outlines assays and techniques for exploration of
      hematopoietic mobilization using mice as a model organism. 

PMID- 25062622
TI  - Cell cycle measurement of mouse hematopoietic stem/progenitor cells.
AB  - Lifelong production of blood cells is sustained by hematopoietic stem cells
      (HSC). HSC reside in a mitotically quiescent state within specialized areas of
      the bone marrow (BM) microenvironment known as the hematopoietic niche (HN). HSC
      enter into active phases of cell cycle in response to intrinsic and extrinsic
      biological cues thereby undergoing differentiation or self-renewal divisions.
      Quiescent and mitotically active HSC have different metabolic states and
      different functional abilities such as engraftment and BM repopulating potential
      following their transplantation into conditioned recipients. Recent studies
      reveal that various cancers also utilize the same mechanisms of quiescence as
      normal stem cells and preserve the root of malignancy thus contributing to
      relapse and metastasis. Therefore, exploring the stem cell behavior and function
      in conjunction with their cell cycle status has significant clinical implications
      in HSC transplantation and in treating cancers. In this chapter, we describe
      methodologies to isolate or analytically measure the frequencies of quiescent
      (G0) and active (G1, S, and G2-M) hematopoietic progenitor and stem cells among
      murine BM cells. 

PMID- 25062623
TI  - Flow cytometric analysis of signaling and apoptosis in hematopoietic stem cells.
AB  - The analysis of protein phosphorylation in hematopoietic stem cells (HSCs)
      provides a powerful tool for studying the cell signaling activities that mediate
      HSC fate decisions, such as self-renewal, differentiation, and apoptosis. The
      first part of this chapter describes a method of intracellular staining for
      phosphorylated proteins in conjunction with membrane staining for multiple
      hematopoietic cell-surface markers, and subsequent flow cytometric analysis of
      protein phosphorylation levels [indicated by mean fluorescence intensity (MFI) of
      specific fluorochromed phospho-antibodies] in primitive hematopoietic cells. The
      second part describes a method for assessing the frequency of apoptosis in HSCs
      using extracellular staining with recombinant Annexin V and 7-Amino-Actinomycin
      (7-AAD). Both parts involve an initial magnetic enrichment of hematopoietic
      stem/progenitor cells from bone marrow. Because of the intracellular detection
      required for the HSC signaling assay, this assay also includes cell fixation and
      permeabilization. Gating strategies for assessing MFI and the frequency of
      Annexin V(+) apoptotic cells in a complex population are also described along
      with representative examples. 

PMID- 25062624
TI  - Gene expression profiling of hematopoietic stem cells (HSCs).
AB  - Transcriptomic analysis to decipher the molecular phenotype of hematopoietic stem
      cells, regulatory mechanisms directing their life cycle, and the molecular
      signals mediating proliferation, mobilization, migration, and differentiation is
      believed to unravel disease-specific disturbances in hematological diseases and
      assist in the development of novel cell-based clinical therapies in this era of
      genomic medicine. The recent advent in genomic tools and technologies is now
      enabling the study of such comprehensive transcriptional characterization of cell
      types in a robust and successful manner. This chapter describes detailed
      protocols for isolating RNA from purified population of hematopoietic cells and
      gene expression profiling of those purified cells using both microarrays
      (Affymetrix) and RNA-Seq technology (Illumina Platform). 

PMID- 25062625
TI  - Measuring microRNA expression in mouse hematopoietic stem cells.
AB  - MicroRNAs (miRNAs) are important regulators of diverse biologic processes. In the
      hematopoietic system, miRNAs have been shown to regulate lineage fate decisions,
      mature immune effector cell function, apoptosis, and cell cycling, and a more
      limited number of miRNAs has been shown to regulate hematopoietic stem cell (HSC)
      self-renewal. Many of these miRNAs were initially identified as candidate
      regulators of HSC function by comparing miRNA expression in hematopoietic stem
      and progenitors cells (HSPCs) to their mature progeny. While the measurement of
      miRNA expression in rare cell populations such as HSCs poses practical challenges
      due to the low amount of RNA present, a number of techniques have been developed
      to measure miRNAs in small numbers of cells. Here, we describe our protocol for
      measuring miRNAs in purified mouse HSCs using a highly sensitive real-time
      quantitative PCR strategy that utilizes microfluidic array cards containing pre
      spotted TaqMan probes that allows the detection of mature miRNAs in small
      reaction volumes. We also describe a simple data analysis method to evaluate
      miRNA expression profiling data using an open-source software package (HTqPCR)
      using mouse HSC miRNA profiling data generated in our lab. 

PMID- 25062626
TI  - DNA methylation profiling of hematopoietic stem cells.
AB  - DNA methylation is a key epigenetic mark that is essential for properly
      functioning hematopoietic stem cells. Determining where functionally relevant DNA
      methylation marks exist in the genome is crucial to understanding the role that
      methylation plays in hematopoiesis. This chapter describes a method to profile
      DNA methylation by selectively enriching methylated DNA sequences that are bound
      in vitro by methyl-binding domain (MBD) proteins. The MBD-pulldown approach
      selects for DNA sequences that have the potential to be "read" by the endogenous
      machinery involved in epigenetic regulation. Furthermore, this approach is
      feasible with very small quantities of DNA, and is compatible with the use of any
      downstream high-throughput sequencing approach. This technique offers a reliable,
      simple, and powerful tool for exploration of the role of DNA methylation in
      hematopoietic stem cells. 

PMID- 25062627
TI  - Metabolic characterization of hematopoietic stem cells.
AB  - An important feature of stem cells is their maintenance in their respective
      hypoxic niche. Survival in this low-oxygen microenvironment requires significant
      metabolic adaptation. We demonstrated that mouse HSCs utilize glycolysis instead
      of mitochondrial oxidative phosphorylation to meet their energy demands. We have
      adapted various tools for characterization of the metabolic properties of
      hematopoietic stem cells (HSCs). These techniques include flow cytometric
      profiling of HSCs based on mitochondrial potential and NADH fluorescence as well
      as measurement of ATP content, oxygen consumption rate, and glycolytic flux in
      purified HSCs. 

PMID- 25062628
TI  - Nanoproteomic assays on hematopoietic stem cells.
AB  - Dysregulation of cytokine signaling pathways is associated with benign and
      malignant hematologic disorders. Improvements in therapy rely on understanding
      the biology of the pathways and the proteins involved. Studying these pathways in
      patient samples is challenging as samples are difficult to obtain, contain fewer
      cells, and are heterogeneous in nature. To address some of these difficulties, we
      have utilized the technique of microcapillary electrophoresis. Using the NanoPro
      1000 system (ProteinSimple) which is built on an automated, capillary-based
      immunoassay platform, we have developed rapid and quantitative assays for
      specific proteins from relatively small sample sizes. The NanoPro provides
      precise and quantitative data of the phosphorylation states of a specific protein
      of interest. We describe our experience with NanoPro assay development and
      optimization with specific application toward understanding aberrant cytokine
      signaling in human leukemia cells. 

PMID- 25062629
TI  - Hematopoietic differentiation of pluripotent stem cells in culture.
AB  - This chapter describes a two-dimensional "monolayer" system for differentiating
      human pluripotent stem cells (PSCs) into "primitive" hematopoietic progenitor
      cells (HPCs) resembling those produced in vivo by the early embryonic yolk sac.
      This experimental system utilizes defined conditions without serum or feeder
      cells. Cytokines are added sequentially to stimulate the formation of mesoderm
      and its subsequent patterning to hematopoietic progenitors. The HPCs produced by
      this protocol have multi-lineage potential (erythroid, megakaryocyte, and
      myeloid) and can be isolated as a homogeneous population for use in standard
      hematopoietic studies including liquid expansion to mature lineages and colony
      assays. In addition, the HPCs can be cryopreserved for distribution or analysis
      at later times. The HPCs generated by this protocol have been used successfully
      to better define intrinsic variation in hematopoietic potential between different
      PSC lines and to model human hematopoietic diseases using patient-derived induced
      pluripotent stem cells. 

PMID- 25062630
TI  - Ex vivo assays to study self-renewal, long-term expansion, and leukemic
      transformation of genetically modified human hematopoietic and patient-derived
      leukemic stem cells.
AB  - With the emergence of the concept of the leukemic stem cell (LSC), assays to
      study them remain pivotal in understanding (leukemic) stem cell biology. Although
      the in vivo NOD-SCID or NSG xenotransplantation model is currently still the
      favored assay of choice in most cases, this system has some limitations as well
      such as its cost-effectiveness, duration, and lack of engraftability of cells
      from some acute myeloid leukemia (AML) patients. Here, we describe in vitro
      assays in which long-term expansion and self-renewal of LSCs isolated from AML
      patients can be evaluated. We have optimized lentiviral transduction procedures
      in order to stably express genes of interest or stably downmodulate genes using
      RNAi in primary AML cells, and these approaches are described in detail here.
      Also, we describe bone marrow stromal coculture systems in which cobblestone area
      forming cell activity, self-renewal, long-term expansion, and in vitro myeloid or
      lymphoid transformation can be evaluated in human CD34(+) cells of fetal or adult
      origin that are engineered to express oncogenes. Together, these tools should
      allow a further molecular elucidation of derailed signal transduction in LSCs. 

PMID- 25062631
TI  - Ex vivo expansion of murine and human hematopoietic stem cells.
AB  - Hematopoietic stem cells have the capacity to self-renew and give rise to the
      entirety of the mature blood and immune system throughout the lifespan of an
      organism. Here, we describe methods to isolate and culture murine bone marrow
      (BM) CD34(-)ckit(+)Sca1(+)Lineage(-) (CD34(-)KSL) hematopoietic stem cells
      (HSCs). We also describe a method to measure functional HSC content via the
      competitive repopulation assay. Furthermore, we summarize methods to isolate and
      culture human CD34(+)CD38(-)Lineage(-) cells which are enriched for human
      hematopoietic stem and progenitor cells. 

PMID- 25062632
TI  - Using microfluidics to investigate hematopoietic stem cell and microniche
      interactions at the single cell level.
AB  - In recent years, microfluidic devices have become widely used in biology, and
      with the advantage of requiring low sample volumes, enables previously
      technologically infeasible experiments in hematopoietic stem cell (HSC) research.
      Here, we introduce a microfluidic device to investigate dynamic interactions
      between HSC and model niches in vitro. The device comprises a pneumatic valve
      which enables the culturing of different types of niche cells in different parts
      of the same device. Single HSCs can then be injected into the microfluidic
      device, manipulated, and placed onto different niches within the same device as
      controlled by the user. Here, we describe the device fabrication method, the HSC
      collection methodology, and the operational procedure for the device. 

PMID- 25062633
TI  - Five-lineage clonal analysis of hematopoietic stem/progenitor cells.
AB  - Hematopoietic stem cells (HSCs) have self-renewal activity and multipotency.
      Clonal analysis and determination of HSC differentiation potential into platelets
      and erythrocytes as well as leukocytes are essential for the study of self
      renewal and lineage commitment in HSC. However, due to technical limitations,
      platelet and erythrocyte differentiation potentials have not been assessed. This
      chapter describes principles and methods for single-cell sorting, single-cell
      transplantation, and identification and quantitative analysis of cell
      contribution to platelets and erythrocytes in addition to leukocytes in mouse
      chimeras. 

PMID- 25062634
TI  - Intravital imaging of hematopoietic stem cells in the mouse skull.
AB  - Over the past 50 years, much insight has been gained into the biology of
      hematopoietic stem cells (HSCs). Much of this information has been gained though
      isolation of specific bone marrow populations, and transplantation into
      irradiated recipients followed by characterization of chimeras months later.
      These studies have yielded insights into the function of HSCs, but have shed
      little light on the interactions of individual stem cells with their environment.
      Characterization of the behavior of single HSCs awaited the use of relatively
      noninvasive intravital microscopy, which allows one to identify rare cells in
      real time and follow them in multiple imaging sessions. Here we describe
      techniques used to image transplanted HSCs in the mouse calvarium using hybrid
      confocal/multi-photon microscopy and second harmonic imaging. For detection,
      fluorescently tagged HSCs are transplanted into a recipient mouse. The
      architecture of the bone marrow can be delineated using a combination of
      fluorescent probes and vascular dyes, second harmonic generation to detect the
      collagen signal from bone, and transgenic recipient mice containing specific
      fluorescent support cell populations. 

PMID- 25062636
TI  - Homing and migration assays of hematopoietic stem/progenitor cells.
AB  - Hematopoietic stem and progenitor cells (HSPCs) reside mainly in bone marrow;
      however, under homeostatic and stressed conditions, HSPCs dynamically change
      their location-either egressing from bone marrow and getting into circulation, a
      process of mobilization; or coming back to the bone marrow, the homing process.
      How to analyze these two processes will be critical for understanding the
      behavior of HSPCs. Here we provide an experimental protocol to monitor and
      analyze homing and migration of HSPCs. 

PMID- 25062635
TI  - Immunodeficient mouse model for human hematopoietic stem cell engraftment and
      immune system development.
AB  - Immunodeficient mice engrafted with human immune systems provide an exciting
      model to study human immunobiology in an in vivo setting without placing patients
      at risk. The essential parameter for creation of these "humanized models" is
      engraftment of human hematopoietic stem cells (HSC) that will allow for optimal
      development of human immune systems. However, there are a number of strategies to
      generate humanized mice and specific protocols can vary significantly among
      different laboratories. Here we describe a protocol for the co-implantation of
      human HSC with autologous fetal liver and thymic tissues into immunodeficient
      mice to create a humanized model with optimal human T cell development. This
      model, often referred to as the Thy/Liv or BLT (bone marrow, liver, thymus)
      mouse, develops a functional human immune system, including HLA-restricted human
      T cells, B cells, and innate immune cells. 

PMID- 25062637
TI  - Retroviral transduction of murine and human hematopoietic progenitors and stem
      cells.
AB  - Genetic modification of cells using retroviral vectors is the method of choice
      when the cell population is difficult to transfect and/or requires persistent
      transgene expression in progeny cells. There are innumerable potential
      applications for these procedures in laboratory research and clinical therapeutic
      interventions. One paradigmatic example is the genetic modification of
      hematopoietic stem and progenitor cells (HSPCs). These are rare nucleated cells
      which reside in a specialized microenvironment within the bone marrow, and have
      the potential to self-renew and/or differentiate into all hematopoietic lineages.
      Due to their enormous regenerative capacity in steady state or under stress
      conditions these cells are routinely used in allogeneic bone marrow
      transplantation to reconstitute the hematopoietic system in patients with
      metabolic, inflammatory, malignant, and other hematologic disorders. For patients
      lacking a matched bone marrow donor, gene therapy of autologous hematopoietic
      stem cells has proven to be an alternative as highlighted recently by several
      successful gene therapy trials. Genetic modification of HSPCs using retrovirus
      vectors requires ex vivo manipulation to efficiently introduce the new genetic
      material into cells (transduction). Optimal culture conditions are essential to
      facilitate this process while preserving the stemness of the cells. The most
      frequently used retroviral vector systems for the genetic modifications of HSPCs
      are derived either from Moloney murine leukemia-virus (Mo-MLV) or the human
      immunodeficiency virus-1 (HIV-1) and are generally termed according to their
      genus gamma-retroviral (gamma-RV) or lentiviral vectors (LV), respectively. This
      chapter describes in a step-by-step fashion some techniques used to produce
      research grade vector supernatants and to obtain purified murine or human
      hematopoietic stem cells for transduction, as well as follow-up methods for
      analysis of transduced cell populations.

PMID- 25062638
TI  - Lentiviral gene transduction of mouse and human hematopoietic stem cells.
AB  - Lentiviral vectors can be used to genetically modify a broad range of cells.
      Hematopoietic stem cells (HSCs) are particularly suitable for lentiviral gene
      augmentation, because these cells can be enriched with relative ease from mouse
      bone marrow and human hematopoietic sources, and in principle require relatively
      limited cell numbers to completely reconstitute the hematopoietic system in vivo.
      Furthermore, lentiviral vectors are very efficient if pseudotyped with broad
      tropism envelope proteins. This chapter focuses on gene modification by the use
      of self-inactivating third-generation human immunodeficiency virus-derived
      lentiviral vectors for ex vivo HSC modification for both mouse and human
      application. 

PMID- 25062639
TI  - High-throughput genomic mapping of vector integration sites in gene therapy
      studies.
AB  - Gene therapy has enormous potential to treat a variety of infectious and genetic
      diseases. To date hundreds of patients worldwide have received hematopoietic cell
      products that have been gene-modified with retrovirus vectors carrying
      therapeutic transgenes, and many patients have been cured or demonstrated disease
      stabilization as a result (Adair et al., Sci Transl Med 4:133ra57, 2012; Biffi et
      al., Science 341:1233158, 2013; Aiuti et al., Science 341:1233151, 2013; Fischer
      et al., Gene 525:170-173, 2013). Unfortunately, for some patients the provirus
      integration dysregulated the expression of nearby genes leading to clonal
      outgrowth and, in some cases, cancer. Thus, the unwanted side effect of
      insertional mutagenesis has become a major concern for retrovirus gene therapy.
      The careful study of retrovirus integration sites (RIS) and the contribution of
      individual gene-modified clones to hematopoietic repopulating cells is of crucial
      importance for all gene therapy studies. Supporting this, the US Food and Drug
      Administration (FDA) has mandated the careful monitoring of RIS in all clinical
      trials of gene therapy. An invaluable method was developed: linear amplification
      mediated-polymerase chain reaction (LAM-PCR) capable of analyzing in vitro and
      complex in vivo samples, capturing valuable genomic information directly flanking
      the site of provirus integration. Linking this method and similar methods to high
      throughput sequencing has now made possible an unprecedented understanding of the
      integration profile of various retrovirus vectors, and allows for sensitive
      monitoring of their safety. It also allows for a detailed comparison of improved
      safety-enhanced gene therapy vectors. An important readout of safety is the
      relative contribution of individual gene-modified repopulating clones. One
      limitation of LAM-PCR is that the ability to capture the relative contribution of
      individual clones is compromised because of the initial linear PCR common to all
      current methods. Here, we describe an improved protocol developed for efficient
      capture, sequencing, and analysis of RIS that preserves gene-modified clonal
      contribution information. We also discuss methods to assess
      dominant/overrepresented gene-modified clones in preclinical and clinical models.

PMID- 25062640
TI  - Barcoded vector libraries and retroviral or lentiviral barcoding of hematopoietic
      stem cells.
AB  - Cellular barcoding is a relatively recent technique aimed at clonal analysis of a
      proliferating cell population of any kind. The method was shown to be
      particularly successful in monitoring clonal contributions of hematopoietic stem
      cells (HSCs). An essential step of the method is retroviral or lentiviral
      labeling of the hematopoietic cells. The unique feature of the method is the
      generation of a vector library containing specific artificial DNA tags, generally
      known as barcodes. The library must satisfy multiple essential requirements.
      Importantly, considering the number of possible variations within the barcode
      sequence, the actual size of the barcoded vector library, and the number of
      clonogenic (stem) cells in the given experiment should be in ratios far from
      saturation. Excessive bias in barcodes frequencies must be avoided, and the
      library size must be assessed prior to the sequencing analysis. The final
      sequencing results must undergo statistical filtering. If all requirements are
      met, the method ensures profound sensitivity and accuracy for monitoring of the
      clonal fluctuations in a wide range of biological experiments. 

PMID- 25062641
TI  - New insight into the epidemiology of rabbit hemorrhagic disease viruses in
      Portugal: retrospective study reveals the circulation of genogroup 5 (G5) in
      Azores and discloses the circulation of G1 and G6 strains in mainland until 2008.
AB  - The genetic relationships between 10 rabbit hemorrhagic disease strains collected
      in Portugal between 2006 and 2013, originated in the mainland and Azorean
      islands, were investigated based on the vp60 gene variability. A genetic
      diversity ranging from 2% to 13% was determined among the 10-vp60 complete
      sequences revealing a significant level of genetic heterogeneity between same
      strains. Phylogenetic Bayesian analysis showed that the Portuguese RHDV strains
      fell within different genogroups, namely G1, G5 and G6. Interestingly, all
      strains obtained from Azores, where RHDV was first detected in 1988, belong to G5
      genogroup. G5 strains, that were not identified in the continent so far, seem to
      be the dominant group in these Atlantic islands. G1-related strains belonging to
      the Iberian group 3 (n=3) and G6 (RHDVa) strains (n=2) were identified among the
      samples originated in mainland which were collected between 2006 and 2008.
      Although the presence of G1 and G6 in Portugal had been shown before, our data
      refines the time of circulation of these strains until at least 2008. In summary,
      this study revises the epidemiological information of RHDV in Portugal since it
      reports for the first time the presence of G5 strains in Azores and demonstrates
      the circulation of G1 and G6 strains in mainland Portugal until the late 2000s. 

PMID- 25062642
TI  - Enhanced conidial thermotolerance and field efficacy of Beauveria bassiana by
      saccharides.
AB  - Insecticide efficacy of Beauveria bassiana conidia was improved by optimizing the
      concentrations of conidial heat-protective saccharides (glucose, sucrose,
      maltose, trehalose, alpha-lactose, and mannitol) using response surface
      methodology. Two field trials in tea gardens were carried out to control
      leafhopper (Empoasca vitis) by spraying B. bassiana conidia together with the
      optimized saccharides (0.26 g glucose, 0.28 g lactose, 0.24 g mannitol per ml).
      In the field studies, B. bassiana conidia were applied to control Empoasca vitis
      with and without saccharides and compared with bifenthrin, a pyrethroid
      insecticide. With the optimal concentrations of saccharides, the conidial
      germination rate reached 72% and the control efficacy of the saccharides group
      (65.7%) was equal to the bifenthrin group (69.4%), which improved by about 55%.

PMID- 25062643
TI  - Editorial overview: Cell organelles.

PMID- 25062644
TI  - Novel interactive effects of darkness and retinoid signaling in the ability to
      form long-term memory following aversive operant conditioning.
AB  - The vitamin A metabolite, retinoic acid, is important for memory formation and
      hippocampal synaptic plasticity in vertebrate species. In our studies in the
      mollusc Lymnaea stagnalis, we have shown that retinoic acid plays a role in
      memory formation following operant conditioning of the aerial respiratory
      behaviour. Inhibition of either retinaldehyde dehydrogenase (RALDH) or the
      retinoid receptors prevents long-term memory (LTM) formation, whereas synthetic
      retinoid receptor agonists promote memory formation by converting intermediate
      term memory (ITM) into LTM. In this study, animals were exposed to constant
      darkness in order to test whether light-sensitive retinoic acid would promote
      memory formation. However, we found that exposure to constant darkness alone (in
      the absence of retinoic acid) enhanced memory formation. To determine whether the
      memory-promoting effects of darkness could override the memory-inhibiting effects
      of the retinoid signaling inhibitors, we exposed snails to RALDH inhibitors or a
      retinoid receptor antagonist in constant darkness. We found that darkness
      overcame the inhibitory effects of RALDH inhibition, but did not overcome the
      inhibitory effects of the retinoid receptor antagonist. We also tested whether
      constant darkness and training affected the mRNA levels of the retinoid metabolic
      enzymes RALDH and Cyp26, or the mRNA levels of the retinoid receptors, but found
      no significant effect. Overall, these data demonstrate an interaction between
      environmental light conditions and the retinoid signaling pathway, which
      influence long-term memory formation in a mollusc. 

PMID- 25062645
TI  - Memory deficits and oxidative stress in cerebral ischemia-reperfusion:
      neuroprotective role of physical exercise and green tea supplementation.
AB  - Ischemic stroke is a major cause of morbidity and mortality all over the world.
      Among impairments observed in survivors there is a significant cognitive learning
      and memory deficit. Neuroprotective strategies are being investigated to minimize
      such deficits after an ischemia event. Here we investigated the neuroprotective
      potential of physical exercise and green tea in an animal model of ischemia
      reperfusion. Eighty male rats were divided in 8 groups and submitted to either
      transient brain ischemia-reperfusion or a sham surgery after 8 weeks of physical
      exercise and/or green tea supplementation. Ischemia-reperfusion was performed by
      bilateral occlusion of the common carotid arteries during 30 min. Later, their
      memory was evaluated in an aversive and in a non-aversive task, and hippocampus
      and prefrontal cortex were removed for biochemical analyses of possible oxidative
      stress effects. Ischemia-reperfusion impaired learning and memory. Reactive
      oxygen species were increased in the hippocampus and prefrontal cortex. Eight
      weeks of physical exercise and/or green tea supplementation before the ischemia
      reperfusion event showed a neuroprotective effect; both treatments in separate or
      together reduced the cognitive deficits and were able to maintain the functional
      levels of antioxidant enzymes and glutathione.

PMID- 25062646
TI  - Intranasal dopamine treatment reinstates object-place memory in aged rats.
AB  - Following oral or IV administration, dopamine (DA) cannot cross the blood-brain
      barrier to a significant extent, but can enter the brain when administered via
      the nasal passages. Intranasal administration of DA was shown to increase
      extracellular DA in the striatum, to have antidepressant action and to improve
      attention and working memory in rats. Here we show that aged (22-24 months old)
      rats are deficient in an object-place learning task, but that this
      learning/memory is intact and comparable with that of adult rats upon pre-trial
      administration of 0.3 mg/kg DA gel into the nasal passages. This result raises
      the possibility of the therapeutic application of intranasal DA treatment for age
      related cognitive disorders.

PMID- 25062647
TI  - Cobblestone mouth: an exuberant oral presentation of pemphigus vegetans.

PMID- 25062648
TI  - The role of new immunosuppressive drugs in nonmelanoma skin cancer in renal
      transplant recipients.
AB  - INTRODUCTION: Nonmelanoma skin cancer (NMSC) is the most common malignancy in
      patients who have received a solid organ transplant. Multiple factors are
      involved in the onset of posttransplant NMSC. OBJECTIVES: To analyze the
      relationship between new immunosuppressive drugs and the onset of NMSC in renal
      transplant recipients. METHOD: This was a combined retrospective and prospective
      observational study in which we studied 289 patients who received a kidney
      transplant between January 1996 and December 2010 at Hospital Universitario
      Doctor Peset in Valencia, Spain. RESULTS: Seventy-three patients (25.2%)
      developed 162 NMSCs over a median follow-up of 72 months. There were no
      statistically significant differences in the onset of NMSC on comparing different
      induction therapy strategies involving monoclonal and polyclonal antibodies.
      NMSCs occurred less frequently in patients treated with mammalian target of
      rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive
      regimens, although the differences were not statistically significant. Three of 5
      patients with recurrent NMSC who were switched from calcineurin inhibitors to
      mTOR inhibitors developed additional NMSCs despite the change. CONCLUSIONS:
      Induction therapy with monoclonal and polyclonal antibodies in renal transplant
      recipients is not associated with an increased risk of NMSC. While mTOR
      inhibitors are associated with a lower risk of posttransplant NMSC, it remains to
      be determined whether a switch to these drugs is useful in the management of
      patients who develop multiple NMSCs.

PMID- 25062650
TI  - Transfer of directional information between the polarization compass and the sun
      compass in desert ants.
AB  - Desert ants, Cataglyphis fortis, perform large foraging excursions during which
      they continuously compute a home vector that allows them to return to the nest on
      the shortest way. This type of navigation, termed path integration, needs a
      compass system and an odometer. Ants use several cues to determine their walking
      direction, two of the most important ones being the sun position and the
      polarization pattern of the sky. We tested whether an information transfer is
      possible from one compass system to the other, which depend on different
      anatomical substrates. Since the sky's polarization pattern is detected by UV
      photoreceptors located in the dorsal rim area (DRA), we used an orange Perspex
      filter that eliminated the UV part of the spectrum to prevent the use of the
      polarization compass. The use of the sun compass could be excluded by appropriate
      screens. In the critical tests the ants had learned a nest-feeder direction with
      e.g. the sun compass only, and were later tested with the polarization compass,
      or vice versa. The results show that a transfer is possible in both directions. 

PMID- 25062651
TI  - Efficacy and safety of weight-based insulin glargine dose titration regimen
      compared with glucose level- and current dose-based regimens in hospitalized
      patients with type 2 diabetes: a randomized, controlled study.
AB  - PURPOSE: Insulin glargine is widely used as basal insulin. However, published
      dose titration regimens for insulin glargine are complex. This study aimed to
      compare the efficacy and safety profile of a user-friendly, weight-based insulin
      glargine dose titration regimen with 2 published regimens. METHODS: A total of
      160 hospitalized patients with hyperglycemia in 3 medical centers were screened.
      Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion
      criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A
      total of 149 patients were randomly assigned to receive weight-based, glucose
      level-based, or dose-based insulin glargine dose titration regimen between
      January 2011 and February 2013. The initial dose of insulin glargine was 0.2
      U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments
      of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was
      titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was,
      respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or >=10 mmol/L. In
      the current dose-based regimen (n = 49), titration was by daily increments of 20%
      of the current dose. The target FBG in all groups was <=7.0 mmol/L. The incidence
      of hypoglycemia was recorded. One-way ANOVA and chi(2) test were used to compare
      data between the 3 groups. FINDINGS: All but 1 patient who required additional
      oral antidiabetic medication completed the study. The mean (SD) time to achieve
      target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days
      with the glucose level-based regimen (P = 0.266). These times were both shorter
      than that achieved with the current dose-based regimen (4.8 [2.8] days; P =
      0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the
      study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20)
      U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current
      dose-based regimen (P = 0.184). The incidence of hypoglycemia was 4.1%, 2.0%, and
      6.3%, respectively (P = 0.557). IMPLICATIONS: The currently proposed weight-based
      insulin glargine dose titration regimen is effective, tolerable, and user
      friendly at achieving FBG target levels in hospitalized patients with
      hyperglycemia.

PMID- 25062652
TI  - Cost of biologics per treated patient across immune-mediated inflammatory disease
      indications in a pharmacy benefit management setting: a retrospective cohort
      study.
AB  - PURPOSE: Pharmacy benefits management companies have emerged as the national
      standard for the management of prescription drugs in the United States. The
      objective of this study was to estimate the annual costs per treated patient of 8
      biologics indicated for select immune-mediated inflammatory diseases: moderate to
      severe rheumatoid arthritis, moderate to severe plaque psoriasis, active
      psoriatic arthritis, and/or active ankylosing spondylitis. METHODS: Using the
      Medco pharmacy benefits-management database, data from patients aged 18 to 63
      years with >=1 claim for abatacept, adalimumab, certolizumab, etanercept,
      golimumab, infliximab, rituximab, or ustekinumab, dated between January 1, 2008
      and August 31, 2011, were collected. Eligible patients were continuously enrolled
      for >=180 days before and 360 days after the date of the first biologic claim
      (index date), and had >=1 claim associated with a diagnosis of rheumatoid
      arthritis, moderate to severe plaque psoriasis, active psoriatic arthritis,
      and/or active ankylosing spondylitis in the 180 days before or 30 days after the
      index date. The annual total costs per treated patient were calculated as the
      total dose of the index biologic and all other biologics for which there was a
      claim in the postindex period, multiplied by the wholesale acquisition cost as of
      October 1, 2013, plus the costs associated with administrations (calculated as
      number of infusions multiplied by the 2013 Medicare Physician Fee Schedule
      costs). FINDINGS: Within the study population (N = 8306; 5356 (64.5%) women, 2950
      men (35.5%), average age: 42.3 years (SD: 10.0)), the most commonly used
      biologics were etanercept (43.1%), adalimumab (31.0%), and infliximab (17.0%),
      which accounted for 91.1% of all biologic prescriptions. Total costs per treated
      patient across indications were as follows: adalimumab, $23,427 to $26,304;
      infliximab, $22,824 to $28,907; and etanercept, $21,468 to $27,748, whereas
      abatacept, certolizumab, golimumab, rituximab, and ustekinumab were associated
      with a larger range: $17,017 to $41,888. IMPLICATIONS: The present study provides
      insight into the prescribing patterns and cost differences among 8 biologic
      agents used for the treatment of immune-mediated inflammatory diseases. This
      information may prove useful when designing a pharmacy benefits-management
      formulary.

PMID- 25062654
TI  - Iatrogenic genitourinary fistula: an 18-year retrospective review of 805
      injuries.
AB  - INTRODUCTION AND HYPOTHESIS: Genitourinary fistula poses a public health
      challenge in areas where women have inadequate access to quality emergency
      obstetric care. Fistulas typically develop during prolonged, obstructed labor,
      but providers can also inadvertently cause a fistula when performing obstetric or
      gynecological surgery. METHODS: This retrospective study analyzes 805 iatrogenic
      fistulas from a series of 5,959 women undergoing genitourinary fistula repair in
      11 countries between 1994 and 2012. Injuries fall into three categories:
      ureteric, vault, and vesico-[utero]/-cervico-vaginal. This analysis considers the
      frequency and characteristics of each type of fistula and the risk factors
      associated with iatrogenic fistula development. RESULTS: In this large series,
      13.2 % of genitourinary fistula repairs were for injuries caused by provider
      error. A range of cadres conducted procedures resulting in iatrogenic fistula.
      Four out of five iatrogenic fistulas developed following surgery for obstetric
      complications: cesarean section, ruptured uterus repair, or hysterectomy for
      ruptured uterus. Others developed during gynecological procedures, most commonly
      hysterectomy. Vesico-[utero]/-cervico-vaginal fistulas were the most common (43.6
      %), followed by ureteric injuries (33.9 %) and vault fistulas (22.5 %). One
      quarter of women with iatrogenic fistulas had previously undergone a laparotomy,
      nearly always a cesarean section. Among these women, one quarter had undergone
      more than one previous cesarean section. CONCLUSIONS: Women with previous
      cesarean sections are at an increased risk of iatrogenic injury. Work
      environments must be adequate to reduce surgical error. Training must emphasize
      the importance of optimal surgical techniques, obstetric decision-making, and
      alternative ways to deliver dead babies. Iatrogenic fistulas should be recognized
      as a distinct genitourinary fistula category.

PMID- 25062655
TI  - Implementation of a standardized digital rectal exam to improve the accuracy of
      rectocele diagnosis.
AB  - INTRODUCTION AND HYPOTHESIS: The standardized evaluation of posterior compartment
      prolapse using the Pelvic Organ Prolapse Quantification (POP-Q) system is
      limited. The primary objective of this study is to develop and validate the
      interexaminer reliability of a new system for assessing the posterior vaginal
      wall for the presence of a rectocele. METHODS: This was a cross-sectional study
      of women presenting to an academic urogynecology clinic. Subjects underwent a
      routine pelvic examination that included a standard POP-Q followed by two
      Standardized Digital Rectal Exams (SDRE) by two different providers, each blinded
      to the other's results. The SDRE measures the distance from the leading edge of a
      posterior bulge to the hymen with a finger in the distal rectum - first visually
      and then an actual measured distance using a marked cotton swab (Q-tip
      measurement). Correlations between examiners for the SDRE and the POP-Q were
      analyzed using Pearson's correlation coefficient (rho). RESULTS: Eight attending
      and fellow urogynecologists examined 50 subjects. Mean age was 57.3 years, mean
      BMI 30.9 kg/m(2), with an overall median POP-Q stage 2 (range 0-3), and median
      posterior POP-Q stage 1 (range 0-3). Overall, 54 % of women had a noteworthy
      rectocele by typical digital rectal exam. Interexaminer correlations with SDRE
      for both the visual assessment (rho = 0.697, p < 0.0001) and the Q-tip
      measurement (rho = 0.767, p = p < 0.001) were strong. The intraexaminer visual
      assessment and the Q-tip measurement were highly correlated (rho = 0.934, p =
      <0.001). CONCLUSION: This standardized rectal examination provides a consistent
      method for the reporting of distal rectoceles that can lend additional
      information to the POP-Q exam.

PMID- 25062653
TI  - BNP and NT-proBNP as prognostic markers in persons with acute decompensated heart
      failure: a systematic review.
AB  - A systematic review was undertaken to examine the evidence for B-type natriuretic
      peptides (BNP and NT-proBNP) as independent predictors of mortality, morbidity,
      or combined mortality and morbidity outcomes in persons with acute decompensated
      heart failure (ADHF). Electronic databases (Medline((r)), EmbaseTM, AMED,
      Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic
      Reviews, and CINAHL) were searched from 1989 to June 2012. Reference lists of
      included articles, systematic reviews, and the gray literature were also
      searched. English language studies were eligible if they included subjects with
      ADHF and measured BNP/NT-proBNP using FDA approved assays. Standardized forms
      were used to select studies, extract data, and assess risk of bias. Seventy-nine
      studies, ranging over followup intervals from 14 days to 7 years, evaluating
      levels of BNP (n = 38), NT-proBNP (n = 35), or both (n = 6) were eligible. The
      majority of studies predicted mortality outcomes for admission BNP/NT-proBNP
      levels, with fewer studies evaluating serial, change from admission, or discharge
      levels. In general, higher levels of admission BNP or NT-proBNP predicted greater
      risk for all outcomes. Decreased levels post-admission predicted decreased risk.
      Overall, these studies were rated as having moderate risk of bias. This
      systematic review shows that BNP and NT-proBNP are independent predictors of
      mortality (all-cause and cardiovascular) in ADHF despite different cutpoints,
      time intervals, and prognostic models. Findings for morbidity and composite
      outcomes were less frequently evaluated and showed inconsistency. Further
      research is required to assess cutpoints for admission, serial measurements,
      change following admission, and discharge levels to assist clinical decision
      making. 

PMID- 25062656
TI  - Pelvic floor awareness and the positive effect of verbal instructions in 958
      women early postdelivery.
AB  - INTRODUCTION AND HYPOTHESIS: It is uncertain how reliable a personal belief is
      about the ability to do pelvic floor muscle (PFM) contractions early postdelivery
      and how instructional feedback affects pelvic floor muscle contraction (PFMC)
      performance. We hypothesize that many women do not have a reliable idea about
      PFMC and that instructional feedback can help improve their control. METHODS:
      Prospective observational study in 958 women (median 30 years) early postdelivery
      PFMC was evaluated with visual observation: an inward movement of the perineum
      was accepted as sign of good contraction. The women who could not show PFMC three
      consecutive times got verbal instructions, and re-evaluation was afterward.
      RESULTS: In 500 women, no inward movement of the perineum was observed: 275 women
      (29%) showed no movement at all, and 225 women (24%) showed some movement but no
      inward displacement. In 33.4%, the personal conviction to be able or not to
      perform PFMC proved false. After verbal instructions, 74% improved their PFMC.
      CONCLUSIONS: The belief of doing correct PFM contraction was false in at least
      one of five postpartum women. Verbal instructions have a positive effect on
      performing PFMC in 73.6% of women.

PMID- 25062657
TI  - Impact of pharmaceutical policy interventions on utilization of antipsychotic
      medicines in Finland and Portugal in times of economic recession: interrupted
      time series analyses.
AB  - OBJECTIVES: To analyze the impacts of pharmaceutical sector policies implemented
      to contain country spending during the economic recession--a reference price
      system in Finland and a mix of policies including changes in reimbursement rates,
      a generic promotion campaign and discounts granted to the public payer in
      Portugal - on utilization of, as a proxy for access to, antipsychotic medicines.
      METHODOLOGY: We obtained monthly IMS Health sales data in standard units of
      antipsychotic medicines in Portugal and Finland for the period January 2007 to
      December 2011. We used an interrupted time series design to estimate changes in
      overall use and generic market shares by comparing pre-policy and post-policy
      levels and trends. RESULTS: Both countries' policy approaches were associated
      with slight, likely unintended, decreases in overall use of antipsychotic
      medicines and with increases in generic market shares of major antipsychotic
      products. In Finland, quetiapine and risperidone generic market shares increased
      substantially (estimates one year post-policy compared to before, quetiapine:
      6.80% [3.92%, 9.68%]; risperidone: 11.13% [6.79%, 15.48%]. The policy
      interventions in Portugal resulted in a substantially increased generic market
      share for amisulpride (estimate one year post-policy compared to before: 22.95%
      [21.01%, 24.90%]; generic risperidone already dominated the market prior to the
      policy interventions. CONCLUSIONS: Different policy approaches to contain
      pharmaceutical expenditures in times of the economic recession in Finland and
      Portugal had intended--increased use of generics--and likely unintended--slightly
      decreased overall sales, possibly consistent with decreased access to needed
      medicines--impacts. These findings highlight the importance of monitoring and
      evaluating the effects of pharmaceutical policy interventions on use of medicines
      and health outcomes.

PMID- 25062659
TI  - Production of a water-soluble fertilizer containing amino acids by solid-state
      fermentation of soybean meal and evaluation of its efficacy on the rapeseed
      growth.
AB  - Soybean meal is a by-product of soybean oil extraction and contains approximately
      44% protein. We performed solid-state fermentation by using Bacillus subtilis
      strain N-2 to produce a water-soluble fertilizer containing amino acids. Strain N
      2 produced a high yield of protease, which transformed the proteins in soybean
      meal into peptide and free amino acids that were dissolved in the fermentation
      products. Based on the Plackett-Burman design, the initial pH of the fermentation
      substrate, number of days of fermentation, and the ratio of liquid to soybean
      meal exhibited significant effects on the recovery of proteins in the resulting
      water-soluble solution. According to the predicted results of the central
      composite design, the highest recovery of soluble proteins (99.072%) was achieved
      at the optimum conditions. Under these conditions, the resulting solution
      contained 50.42% small peptides and 7.9% poly-gamma-glutamic acid (gamma-PGA).
      The water-soluble fertilizer robustly increased the activity of the rapeseed root
      system, chlorophyll content, leaf area, shoot dry weight, root length, and root
      weight at a concentration of 0.25% (w/v). This methodology offers a value-added
      use of soybean meal. 

PMID- 25062658
TI  - Glycosylation-related genes in NS0 cells are insensitive to moderately elevated
      ammonium concentrations.
AB  - NS0 and Chinese hamster ovary (CHO) cell lines are used to produce recombinant
      proteins for human therapeutics; however, ammonium accumulation can negatively
      impact cell growth, recombinant protein production, and protein glycosylation. To
      improve product quality and decrease costs, the relationship between ammonium and
      protein glycosylation needs to be elucidated. While ammonium has been shown to
      adversely affect glycosylation-related gene expression in CHO cells, NS0 studies
      have not been performed. Therefore, this study sought to determine if
      glycosylation in NS0 cells were ammonium-sensitive at the gene expression level.
      Using a DNA microarray that contained mouse glycosylation-related and
      housekeeping genes, these genes were analyzed in response to various culture
      conditions - elevated ammonium, elevated salt, and elevated ammonium with
      proline. Surprisingly, no significant differences in gene expression levels were
      observed between the control and these conditions. Further, the elevated ammonium
      cultures were analyzed using real-time quantitative reverse transcriptase PCR
      (qRT-PCR) for key glycosylation genes, and the qRT-PCR results corroborated the
      DNA microarray results, demonstrating that NS0 cells are ammonium-insensitive at
      the gene expression level. Since NS0 are known to have elevated nucleotide sugar
      pools under ammonium stress, and none of the genes directly responsible for these
      metabolic pools were changed, consequently cellular control at the translational
      or substrate-level must be responsible for the universally observed decreased
      glycosylation quality under elevated ammonium. 

PMID- 25062660
TI  - Circadian rhythms in the cell cycle and biomass composition of Neochloris
      oleoabundans under nitrogen limitation.
AB  - The circadian clock schedules processes in microalgae cells at suitable times in
      the day/night cycle. To gain knowledge about these biological time schedules,
      Neochloris oleoabundans was grown under constant light conditions and nitrogen
      limitation. Under these constant conditions, the only variable was the circadian
      clock. The results were compared to previous work done under nitrogen-replete
      conditions, in order to determine the effect of N-limitation on circadian rhythms
      in the cell cycle and biomass composition of N. oleoabundans. The circadian clock
      was not affected by nitrogen-limitation, and cell division was timed in the
      natural night, despite of constant light conditions. However, because of nitrogen
      limitation, not the entire population was able to divide every day. Two
      subpopulations were observed, which divided alternately every other day. This
      caused oscillations in biomass yield and composition. Starch and total fatty
      acids (TFA) were accumulated during the day. Also, fatty acid composition changed
      during the cell cycle. Neutral lipids were built up during the day, especially in
      cells that were arrested in their cell cycle (G2 and G3). These findings give
      insight in the influence of circadian rhythms on the cell cycle and biomass
      composition. 

PMID- 25062661
TI  - Genome mining and functional genomics for siderophore production in Aspergillus
      niger.
AB  - Iron is an essential metal for many organisms, but the biologically relevant form
      of iron is scarce because of rapid oxidation resulting in low solubility.
      Simultaneously, excessive accumulation of iron is toxic. Consequently, iron
      uptake is a highly controlled process. In most fungal species, siderophores play
      a central role in iron handling. Siderophores are small iron-specific chelators
      that can be secreted to scavenge environmental iron or bind intracellular iron
      with high affinity. A second high-affinity iron uptake mechanism is reductive
      iron assimilation (RIA). As shown in Aspergillus fumigatus and Aspergillus
      nidulans, synthesis of siderophores in Aspergilli is predominantly under control
      of the transcription factors SreA and HapX, which are connected by a negative
      transcriptional feedback loop. Abolishing this fine-tuned regulation corroborates
      iron homeostasis, including heme biosynthesis, which could be biotechnologically
      of interest, e.g. the heterologous production of heme-dependent peroxidases.
      Aspergillus niger genome inspection identified orthologues of several genes
      relevant for RIA and siderophore metabolism, as well as sreA and hapX.
      Interestingly, genes related to synthesis of the common fungal extracellular
      siderophore triacetylfusarinine C were absent. Reverse-phase high-performance
      liquid chromatography (HPLC) confirmed the absence of triacetylfusarinine C, and
      demonstrated that the major secreted siderophores of A. niger are coprogen B and
      ferrichrome, which is also the dominant intracellular siderophore. In A. niger
      wild type grown under iron-replete conditions, the expression of genes involved
      in coprogen biosynthesis and RIA was low in the exponential growth phase but
      significantly induced during ascospore germination. Deletion of sreA in A. niger
      resulted in elevated iron uptake and increased cellular ferrichrome accumulation.
      Increased sensitivity toward phleomycin and high iron concentration reflected the
      toxic effects of excessive iron uptake. Moreover, SreA-deficiency resulted in
      increased accumulation of heme intermediates, but no significant increase in heme
      content. Together with the upregulation of several heme biosynthesis genes, these
      results reveal a complex heme regulatory mechanism. 

PMID- 25062662
TI  - Knee moment and shear force are correlated with femoral tunnel orientation after
      single-bundle anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Increasing evidence has shown that anatomic single-bundle anterior
      cruciate ligament reconstruction (ACLR) better restores normal knee kinematics
      and functionality than nonanatomic ACLR. Whether anatomic reconstruction results
      in better knee kinetics during daily activities has not been fully investigated.
      PURPOSE: To assess the relationship between femoral tunnel angle and kinetic
      parameters of the knee joint during walking after single-bundle ACLR and to
      compare the radiographic and kinetic results of patients who underwent anatomic
      ACLR with those of patients who underwent nonanatomic ACLR. STUDY DESIGN:
      Controlled laboratory study. METHODS: Twenty-one patients who underwent
      unilateral ACLR were recruited, and 20 healthy subjects from a previous study
      were used as a control group. All surgical procedures were performed by a single
      surgeon, 11 using the transtibial (TT) technique and 10 using the anteromedial
      portal (AMP) technique. Femoral tunnel orientation was measured from posterior-to
      anterior radiographs. Dynamic knee joint moments and shear forces during gait
      were evaluated using 3-dimensional motion analysis and inverse dynamics.
      Relationships between femoral tunnel angles and kinetic results were evaluated
      via linear regression. Results were compared between 2 ACLR groups and controls
      using 1-way analysis of variance. RESULTS: Femoral tunnel angle had significant
      correlations with peak external knee flexion moment and posterior shear force
      during early stance. The TT group had a significantly smaller (more vertical)
      mean femoral tunnel angle (19.4 degrees  +/- 4.1 degrees ) than the AMP group
      (36.4 degrees  +/- 5.8 degrees ). Significant reductions were found in the
      normalized peak external knee flexion moment (TT, 0.15 +/- 0.12 Nm/kg.m; AMP,
      0.25 +/- 0.12 Nm/kg.m; control, 0.25 +/- 0.16 Nm/kg.m) (P = .032) and posterior
      shear force (TT, 0.64 +/- 0.55 N/kg; AMP, 1.10 +/- 0.58 N/kg; control, 1.35 +/-
      0.55 N/kg) (P = .024) in the TT group compared with controls, but not in the AMP
      group. Moreover, a significantly greater medial shear force was found in the TT
      group during the late stance phase (TT, 1.08 +/- 0.32 N/kg; AMP, 0.89 +/- 0.26
      N/kg; control, 0.83 +/- 0.22 N/kg) (P = .038). A greater peak external knee
      adduction moment was found in both ACL groups during the early stance phase (TT,
      0.25 +/- 0.07 Nm/kg.m; AMP, 0.25 +/- 0.07 Nm/kg.m; control, 0.19 +/- 0.05
      Nm/kg.m) (P < .01). CONCLUSION: Knee joint kinetic changes are seen within months
      (~10 months) after ACLR. This study revealed significant relationships between
      femoral tunnel orientation and postoperative knee joint flexion moment and
      posterior shear force during walking. The AMP technique provides better
      restoration of these knee kinetic parameters compared with the TT technique at
      this postoperative time point. CLINICAL RELEVANCE: The femoral tunnel angle
      measured from plain radiographs can be used as an important metric of
      postoperative knee joint kinetics. This information provides a better
      understanding of the knee joint's biomechanical environment after ACLR using
      commonly used single-bundle techniques.

PMID- 25062663
TI  - Simultaneous tissue profiling of eicosanoid and endocannabinoid lipid families in
      a rat model of osteoarthritis.
AB  - We describe a novel LC method for the simultaneous and quantitative profiling of
      43 oxylipins including eicosanoids, endocannabinoids, and structurally related
      bioactive lipids with modified acyl groups. The LC-MS/MS method uses switching at
      a defined time between negative and positive electrospray ionization modes to
      achieve optimal detection sensitivity for all the lipids. The validated method is
      linear over a range of 0.01-5 nmol/g (0.1-50 nmol/g for 2-arachidonoyl glycerol)
      with intra- and interday precision and accuracy between 1.38 and 26.76% and 85.22
      and 114.3%, respectively. The method successfully quantified bioactive lipids in
      different tissue types in the rat, including spinal cord, dorsal root ganglia
      (DRGs), knee joint, brain, and plasma. Distinct regional differences in the
      pattern of lipid measured between tissue types were observed using principle
      component analysis. The method was applied to analyze tissue samples from an
      established preclinical rat model of osteoarthritis (OA) pain and showed that
      levels of 12-hydroxyeicosatetraenoic acid were significantly increased in the OA
      rat knee joint compared with controls, and that 15-hydroxyeicosatetraenoic acid
      was significantly increased in the DRGs in the model of OA compared with
      controls. The developed LC-MS/MS method has the potential to provide detailed
      pathway profiling in tissues and biofluids where the disruption of bioactive
      oxylipins may be involved in disease states. 

PMID- 25062665
TI  - Pediatric medial epicondyle fractures with intra-articular elbow incarceration.
AB  - BACKGROUND: Intra-articular incarceration of the epicondylar fragment occurs in 5
      18 % of all cases of medial epicondyle fracture. It requires stable fixation to
      allow early motion, since elbow stiffness is the most common complication
      following medial epicondyle fracture. In this retrospective study, we report the
      clinical and functional outcomes and the complications that occurred following
      open reduction and screw fixation of medial epicondyle fractures with intra
      articular fragment incarceration. METHODS: Thirteen children who had a fracture
      of the medial epicondyle with incarceration of the fragment in the elbow joint
      (type III) were surgically treated in our university hospital between 1998 and
      2012. There were eight male and five female patients. The mean age at the time of
      injury was 13 years (range 9-16). Operative treatment consisted of open reduction
      and internal fixation with one or two 4.0-mm cannulated screws under fluoroscopic
      control. RESULTS: All of the patients were clinically reviewed at an average
      follow-up of 29 months. The overall range of motion limitation was about 5
      degrees  for flexion-extension and 2 degrees  for pronation-supination. The score
      was excellent in all patients (mean 96.3). Complications occurred in four (31 %)
      children: two cases of symptomatic screw head prominence, irritation with partial
      lesion of the distal triceps myotendinous junction in one patient, and median
      nerve entrapment syndrome in one patient. CONCLUSIONS: In conclusion, open
      reduction and screw fixation yielded excellent clinical and functional outcomes
      for the treatment of medial epicondyle fractures with intra-articular fragment
      incarceration. However, particular attention is should be paid when treating
      these potentially serious injuries in order to minimize the risk of possible
      complications. LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25062666
TI  - A predictive model of the cat cortical connectome based on cytoarchitecture and
      distance.
AB  - Information processing in the brain is strongly constrained by anatomical
      connectivity. However, the principles governing the organization of
      corticocortical connections remain elusive. Here, we tested three models of
      relationships between the organization of cortical structure and features of
      connections linking 49 areas of the cat cerebral cortex. Factors taken into
      account were relative cytoarchitectonic differentiation ('structural model'),
      relative spatial position ('distance model'), or relative hierarchical position
      ('hierarchical model') of the areas. Cytoarchitectonic differentiation and
      spatial distance (themselves uncorrelated) correlated strongly with the existence
      of inter-areal connections, whereas no correlation was found with relative
      hierarchical position. Moreover, a strong correlation was observed between
      patterns of laminar projection origin or termination and cytoarchitectonic
      differentiation. Additionally, cytoarchitectonic differentiation correlated with
      the absolute number of corticocortical connections formed by areas, and varied
      characteristically between different cortical subnetworks, including a 'rich
      club' module of hub areas. Thus, connections between areas of the cat cerebral
      cortex can, to a large part, be explained by the two independent factors of
      relative cytoarchitectonic differentiation and spatial distance of brain regions.
      As both the structural and distance model were originally formulated in the
      macaque monkey, their applicability in another mammalian species suggests a
      general principle of global cortical organization. 

PMID- 25062667
TI  - Hepatocellular carcinoma specific graded prognostic assessment can predict
      outcomes for patients with brain metastases from hepatocellular carcinoma.
AB  - Stratifying patients with brain metastasis (BM) from hepatocellular carcinoma
      (HCC) by prognostic factors can be useful when making treatment decisions.
      Nevertheless, a diagnosis-specific graded prognostic assessment (GPA) for HCC has
      not been well established. We retrospectively reviewed the data from 118 HCC
      patients newly diagnosed with BM at the Yonsei University Health System between
      1985 and 2011. After univariate and multivariate analyses of prognostic factors,
      those shown to significantly affect survival were used to develop a HCC-specific
      GPA (HCC-GPA) index. The median overall survival after BM in all patients was 6.1
      weeks (95% confidence interval 4.8-7.4 weeks). Using the prognostic factors
      identified via multivariate analysis, we developed a HCC-GPA index, including
      number of brain metastases (single: 0.5, multiple: 0 points), alpha-feto protein
      (<400 ng/mL: 0.5, >=400 ng/mL: 0 points), and Child-Pugh-Score (A: 3, B: 2, C: 0
      points). There were no survival differences for age, sex, performance status, and
      time interval from initial diagnosis to development of BM. Median survival times
      from BM were discriminable when applying the HCC-GPA scoring system: 1.7, 3.2,
      7.9, and 27.0 weeks for HCC-GPA scores of 0-1.0 (N = 16), 1.5-2.5 (N = 32), 3.0
      3.5 (N = 49), and 4.0 (N = 21), respectively (P < 0.001). Although the prognoses
      of patients with BM from HCC are dismal, the newly developed HCC-GPA index can be
      used to discriminate the expected prognoses thereof. Moreover, the index may hold
      value as a tool for selecting patients who may be good candidates for active
      local treatment.

PMID- 25062669
TI  - Venous thromboembolism in high grade glioma among surgical patients: results from
      a single center over a 10 year period.
AB  - Patients with high-grade glioma are at elevated risk of venous thromboembolism
      (VTE). The relationship between VTE and survival in glioma patients remains
      unclear, as does the optimal protocol for chemoprophylaxis. The purpose of this
      study was to assessthe incidence of and risk factors associated with VTE in
      patients with high-grade glioma, and the correlation between VTE and survival in
      this population. Furthermore, we sought to define a protocol for perioperative
      DVT prophylaxis. This was a retrospective review of patients who underwent
      craniotomy for resection of high-grade glioma (WHO grade III or IV) at
      Northwestern University between 1999 and 2010. A total of 336 patients met
      inclusion criteria. 53 patients developed postoperative VTE (15.7 %). Median
      survival was 12.0 months and was not significantly different between VTE(+) and
      VTE(-) patients. Demographics and surgical factors were not significantly
      correlated with VTE development. Prior history of VTE was highly predictive of
      postoperative VTE (OR 7.1, p < .01), as was seizure (OR 2.4, p = .005). Increased
      duration of postoperative ICU stay was also a risk factor for VTE (p = .025). 25
      patients in our study received prophylactic anticoagulation(pAC) with either
      heparin or enoxaparin. Early initiation of pAC was associated with decreased
      incidence of VTE (p = .042). There were no hemorrhagic complications in patients
      receiving pAC. VTE is a common complication in high-grade glioma patients. Early
      initiation of anticoagulation is safe and may decrease the risk of VTE. We
      recommend initiation of chemoprophylaxis on postoperative day 1 in patients
      without contraindication.

PMID- 25062668
TI  - Cell density modulates SHC3 expression and survival of human glioblastoma cells
      through Fak activation.
AB  - Shc3 protein levels are high in human glioblastoma but they decrease in vitro. We
      found that SHC3 mRNA and protein increased when glioblastoma cells grew as
      multicellular tumor spheroid (MTS). Shc3 expression was also induced in adherent
      cultures by increasing cell density. Among the Shc family members, only Shc2 and
      Shc3 increased with cell density. Shc3 and focal adhesion kinase (Fak) interact
      as shown by co-immunoprecipitation. Inhibition of Fak activation reduced Shc3
      increase and MTS formation and changed Shc3 phosphorylation pattern. Our results
      suggest that in gliomas cell density modulates Shc3 protein levels and its
      activity, at least in part, through Fak activation. 

PMID- 25062670
TI  - Evaluation of adenoviral vascular endothelial growth factor-activated
      chitosan/hydroxyapatite scaffold for engineering vascularized bone tissue using
      human osteoblasts: In vitro and in vivo studies.
AB  - Bone tissue is dependent on an efficient blood supply to ensure delivery of
      nutrients and oxygen. One method to acquire a vascular-engineered bone tissue
      could be the use of an angiogenic gene-activated scaffold. In the current study,
      porous chitosan/hydroxyapatite (C/HA) scaffolds were fabricated via freeze-drying
      with desired pore size, and then combined with the adenoviral vector encoding
      vascular endothelial growth factor and green fluorescence protein (Ad-VEGF).
      Human osteoblasts were cultured and seeded on characterized scaffolds. The
      attachment, proliferation, and differentiation of cells on gene-activated and
      unactivated C/HA scaffolds were evaluated in vitro and in vivo by histo- and
      immunohistochemistry. Findings confirmed that human osteoblasts cultured on gene
      activated C/HA scaffold secreted vascular endothelial growth factor, besides
      maintaining its characteristic phenotype with specific extracellular matrix
      production. In vivo experiments indicated that scaffolds were tissue
      biocompatible, and that gene-activated scaffold provided a suitable environment
      for neovessel formation by recruiting host endothelial cells into the newly
      forming ectopic bone-like tissue. This study revealed that the Ad-VEGF-activated
      C/HA composite scaffold has potential for vascular bone regeneration
      applications. 

PMID- 25062671
TI  - Bilateral absence of mental foramen in a living human subject.
AB  - The mental foramen, through which the mental nerve emerges, is an important
      anatomic landmark in odonto-stomatology. Knowing its anatomic variations,
      according to the ethnic group or age, is essential when performing local
      anesthesia or implant and orthognathic surgeries. Besides the presence of a
      supernumerary foramen and variations in its location, numerous topographies have
      been described such as unilateral or bilateral triple foramina, hypoplasia or
      agenesis. The case reported here is extremely rare because it has been observed
      in a living and asymptomatic patient whose scan shows a bilateral absence of
      mental foramen. 

PMID- 25062672
TI  - A brief prehistory of Huntington's disease.

PMID- 25062673
TI  - Huntingtin interactions with membrane phospholipids: strategic targets for
      therapeutic intervention?
AB  - The Huntington's disease gene encodes the protein huntingtin (Htt), a soluble
      protein that largely distributes to the cytoplasm where about half the protein is
      found in association with membranes. Early studies on Huntington's disease
      patients suggested changes in membrane phospholipids. Furthermore, changes in
      phospholipid biosynthetic enzymes have been found in HD cell models using genetic
      methods. Recent investigations prove that Htt associates with membranes by direct
      interactions with phospholipids in membranes. Htt contains at least two membrane
      binding domains, which may work in concert with each other, to target to the
      appropriate intracellular membranes for diverse functions. Htt has a particular
      affinity for a specific class of phospholipids called phosphatidylinositol
      phosphates; individual species of these phospholipids propagate signals promoting
      cell survival and regulating changes in morphology. Mutant Htt fragments can
      disrupt synthetic phospholipid bilayers and full-length mutant Htt shows
      increased binding to numerous phospholipids, supporting the idea that mutant Htt
      can introduce pathology at the level of phospholipid interactions. There is a
      great potential to develop therapeutic agents since numerous enzymes regulate the
      both the biosynthesis/metabolism of lipids and the post-translational
      modifications of Htt that direct membrane interactions. Understanding the
      relationship of Htt with membrane phospholipids, and the impact of mutant Htt on
      membrane-related functions and lipid metabolism, may help identify new modes of
      therapeutic intervention for Huntington's disease. 

PMID- 25062674
TI  - Cardiac Dysautonomia in Huntington's Disease.
AB  - Huntington's disease is a fatal, hereditary, neurodegenerative disorder best
      known for its clinical triad of progressive motor impairment, cognitive deficits
      and psychiatric disturbances. Although a disease of the central nervous system,
      mortality surveys indicate that heart disease is a leading cause of death. The
      nature of such cardiac abnormalities remains unknown. Clinical findings indicate
      a high prevalence of autonomic nervous system dysfunction - dysautonomia - which
      may be a result of pathology of the central autonomic network. Dysautonomia can
      have profound effects on cardiac health, and pronounced autonomic dysfunction can
      be associated with neurogenic arrhythmias and sudden cardiac death. Significant
      advances in the knowledge of neural mechanisms in cardiac disease have recently
      been made which further aid our understanding of cardiac mortality in
      Huntington's disease. Even so, despite the evidence of aberrant autonomic
      activity the potential cardiac consequences of autonomic dysfunction have been
      somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias
      have been part of the exclusion criteria in clinical autonomic Huntington's
      disease research. A comprehensive analysis of cardiac function in Huntington's
      disease patients is warranted. Further experimental and clinical studies are
      needed to clarify how the autonomic nervous system is controlled and regulated in
      higher, central areas of the brain - and how these regions may be altered in
      neurological pathology, such as Huntington's disease. Ultimately, research will
      hopefully result in an improvement of management with the aim of preventing early
      death in Huntington's disease from cardiac causes. 

PMID- 25062675
TI  - Genome-wide increase in histone H2A ubiquitylation in a mouse model of
      Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder with
      selective vulnerability of striatal neurons and involves extensive
      transcriptional dysregulation early in the disease process. Previous work in cell
      and mouse models has shown that histone modifications are altered in HD.
      Specifically, monoubiquitylated histone H2A (uH2A) is present at the promoters of
      downregulated genes which led to the hypothesis that uH2A plays a role in
      transcriptional silencing in HD. OBJECTIVE: To broaden our view of uH2A function
      in transcription in HD, we examined genome-wide binding sites of uH2A in 12-week
      old striatal tissue from R6/2 transgenic HD mouse model. METHODS: We used
      chromatin immunoprecipitation followed by genomic promoter microarray
      hybridization (ChIP-chip) and then interrogated how these binding sites correlate
      with transcribed genes. RESULTS: Our analysis reveals that, while uH2A levels are
      globally increased at the genome in the transgenic (TG) striatum, uH2A
      localization at a gene did not strongly correlate with the absence of its
      transcript. Furthermore, analysis of differential ubiquitylation in wild-type
      (WT) and TG striata did not reveal the expected enrichment of uH2A at genes with
      decreased expression in the TG striatum. CONCLUSIONS: This first description of
      genome-wide localization of uH2A in an HD model reveals that monoubiquitylation
      of histone H2A may not function at the level of the individual gene but may
      rather influence transcription through global chromatin structure.

PMID- 25062676
TI  - Further molecular characterisation of the OVT73 transgenic sheep model of
      Huntington's disease identifies cortical aggregates.
AB  - BACKGROUND: Huntington's disease is a neurodegenerative disorder, typically with
      clinical manifestations in adult years, caused by an expanded polyglutamine
      coding repeat in HTT. There are no treatments that delay or prevent the onset or
      progression of this devastating disease. OBJECTIVE AND METHODS: In order to study
      its pre-symptomatic molecular progression and provide a large mammalian model for
      determining natural history of the disease and for therapeutic testing, we
      generated and previously reported on lines of transgenic sheep carrying a full
      length human HTT cDNA transgene, with expression driven by a minimal HTT
      promoter. We report here further characterization of our preferred line, OVT73.
      RESULTS: This line reliably expresses the expanded human huntingtin protein at
      modest, but readily detectable levels throughout the brain, including the
      striatum and cortex. Transmission of the 73 unit glutamine coding repeat was
      relatively stable over three generations. At the first time-point of a
      longitudinal study, animals sacrificed at 6 months (7 transgenic, 7 control)
      showed reduced striatum GABAA alpha1 receptor, and globus pallidus leu-enkephalin
      immunoreactivity. Two of three 18 month old animals sacrificed revealed cortical
      neuropil aggregates. Furthermore, neuronal intranuclear inclusions were
      identified in the piriform cortex of a single 36 month old animal in addition to
      cortical neuropil aggregates. CONCLUSIONS: Taken together, these data indicate
      that the OVT73 transgenic sheep line will progressively reveal early HD pathology
      and allow therapeutic testing over a period of time relevant to human patients.

PMID- 25062677
TI  - The effect of interference on temporal order memory in premanifest and manifest
      Huntington's disease.
AB  - BACKGROUND: Frontal-striatal dysfunction has been linked to cognitive impairment
      in Huntington's disease (HD). The frontal lobes play a role in memory for the
      temporal order in which items occur in a sequence. However, little is known about
      temporal order memory in HD or how it may be affected by interference. OBJECTIVE:
      The study assessed temporal order memory in patients with manifest HD (n = 20),
      premanifest gene carriers for HD (Pre-HD; n = 18), and controls (n = 25) using a
      computerized radial 8-arm maze. METHODS: On the sample phase of each trial,
      participants viewed a random sequence of circles appearing one at a time at the
      end of each arm. On the choice phase, participants viewed two sample phase
      circles and chose the circle occurring earliest in the sequence. Manipulations of
      the temporal lag (defined as the number of circles occurring in the sample phase
      sequence between the two choice phase circles) were conducted to systematically
      vary interference. Temporally proximal lags were hypothesized to generate more
      interference relative to temporally distal lags. RESULTS: The Pre-HD group was
      significantly impaired (p < 0.05) compared to controls on proximal temporal lags
      (high interference) but matched controls on distal lags (low interference). HD
      patients improved as a function of increased lag but demonstrated significant
      impairments (p < 0.05) across lags relative to controls. CONCLUSIONS: Temporal
      order memory is differentially affected by interference during the premanifest
      and manifest stages of HD. The study identifies a fundamental, yet relatively
      unexamined, deficit associated with HD.

PMID- 25062678
TI  - Episodic memory decline in Huntington's disease, a binding deficit?
AB  - BACKGROUND: Huntington's disease (HD) is characterized by episodic memory
      deterioration. OBJECTIVE: Our paper investigates the cognitive mechanisms that
      might underlie this decline. To this aim, we tested two executive hypotheses, the
      binding and the inhibition hypotheses. METHODS: Fifteen HD patients (Mean
      Cytosine-Adenine-Guanine repeats = 44.93, SD = 2.82), and eighteen controls
      matched for age, gender and education were assessed with a neuropsychological
      battery tapping episodic memory and several executive functions, including
      binding and inhibition. RESULTS: Episodic decline in patients with HD was only
      related to binding performance. CONCLUSIONS: Our study shows that HD patients
      suffer from a perturbation of the associative or integrative mechanisms
      responsible for the combination of different memory features into complex
      episodic representations. Damage to frontal-hippocampal circuitry in HD is likely
      to be responsible for this impairment.

PMID- 25062679
TI  - A psychometric comparison of two carer quality of life questionnaires in
      Huntington's disease: implications for neurodegenerative disorders.
AB  - BACKGROUND: The carer impact of neurodegenerative disorders such as Huntington's
      disease (HD) is vast. Attempts to measure carer QoL in neurodegenerative
      disorders include the three-dimensional (Practical aspects of Caregiving, PC;
      Satisfaction with Life, SL; Feelings about Living with Huntington's disease, FL)
      Huntington's Disease Quality of Life Battery for Carers (HDQoL-C) and the
      unidimensional Alzheimer's Carer's Quality of Life Inventory (ACQLI). However,
      evidence regarding their psychometric properties is sparse. OBJECTIVES: To test
      and compare the psychometric properties of the HDQoL-C, its short-form, and the
      ACQLI among HD carers. METHODS: Data from 61 HD carers (36 women; mean age, 55)
      were analysed using traditional psychometric methods. RESULTS: Data completeness
      was good (>95% computable scale scores) but compromised for the PC and total
      HDQoL-C scales (<=80% computable scale scores). Scaling assumptions were
      supported for the SL and ACQLI scales (corrected item-total correlations >=0.38;
      scaling success rates, 94-100%) but not for the PC, FL or total HDQoL-C scales
      (corrected item-total correlations >=0.08; scaling success rates, 39-62%).
      Floor/ceiling effects were <=9.8%. Reliabilities were >=0.84, except for the PC
      scale (0.62). CONCLUSIONS: The HDQoL-C failed to exhibit suitability as a HD
      carer outcome measure, as two of its three scales did not meet basic psychometric
      criteria. The third scale (SL) did not outperform the ACQLI. This suggests that
      carer impact is not disease specific across neurodegenerative disorders.

PMID- 25062680
TI  - Euthanasia and advance directives in Huntington's disease: qualitative analysis
      of interviews with patients.
AB  - BACKGROUND: In the literature there are few reports on euthanasia or physician
      assisted suicide (PAS) or other matters concerning the end-of-life in patients
      with Huntington's disease (HD), although clinical experience suggests these
      issues do arise. OBJECTIVE: To obtain in-depth information about patients'
      thoughts on and attitudes to euthanasia, PAS and the use of advance directives in
      HD. To assess the difficulties patients encounter when thinking about end-of-life
      wishes. METHODS: Semi-structured in-depth interviews with 14 unselected HD
      patients from our out-patient clinic based on a topic list. Qualitative analysis
      of the interviews based on grounded theory. RESULTS: We identified three patterns
      in our group of respondents: patients with distinct wishes, with general wishes
      and ideas and patients with no wishes. The most important frame of reference
      regarding end-of-life wishes in HD patients or known gene carriers is the
      experience with an affected parent. Family is important when thinking about the
      end of life and advance directives, even more so than the patient's physician.
      Knowledge about the (requirements of) law is limited. CONCLUSIONS: The majority
      of interviewees expressed some kind of wish regarding end of life, probably more
      than they had revealed to their physician, but were sometimes hesitant to discuss
      it. Knowledge on how to deal with wishes, advance directives and response shift
      is limited. In general, patients underestimate the requirement for sound
      professional support when considering euthanasia or PAS and the value of an
      advance directive. In an attempt to improve knowledge and communication about end
      of-life issues, physicians should ask the patient directly about their wishes.

PMID- 25062681
TI  - Arteries masquerading as varicose veins: A trap for phlebologists.
AB  - Ultrasound guided sclerotherapy may be complicated by intra-arterial injections
      resulting in significant tissue necrosis. Here, we present a 69-year-old man with
      a history of right small saphenous vein "stripping", presenting for the treatment
      of symptomatic lower limb varicose veins. Duplex ultrasound of the right lower
      limb outlined the pathway of venous incompetence. Despite the history of
      "stripping", the small saphenous vein was present but the sapheno-popliteal
      junction was ligated at the level of the knee crease. No other unusual findings
      were reported at the time. During ultrasound guided sclerotherapy, subcutaneous
      vessels of the right posterior calf were noted to be pulsatile on B-mode
      ultrasound. Treatment was interrupted. Subsequent angiography and sonography
      showed absence of the right distal popliteal artery. A cluster of subcutaneous
      vessels of the right medial and posterior calf were found to be arterial
      collaterals masquerading as varicose veins. Injection sclerotherapy of these
      vessels would have resulted in significant tissue loss. This case highlights the
      importance of vigilance at the time of treatment and the invaluable role of
      ultrasound in guiding endovenous interventions. 

PMID- 25062682
TI  - Initial complications and factors related to prehospital mortality in acute
      myocardial infarction with ST segment elevation.
AB  - OBJECTIVE: Hospital mortality in myocardial infarction ST-elevation myocardial
      infarction has decreased in recent years, in contrast to prehospital mortality.
      Our objective was to determine initial complications and factors related to
      prehospital mortality in patients with acute myocardial infarction with ST
      segment elevation (STEMI). METHODS: Observational study based on a prospective
      continuous register of patients of any age attended by out-of-hospital emergency
      teams in Andalusia between January 2006 and June 2009. This includes patients
      with acute coronary syndrome-like symptoms whose initial ECG showed ST elevation
      or presumably new left bundle branch block (LBBB). Epidemiological, prehospital
      data and final diagnostic were recorded. The study included all patients with
      STEMI on the register, without age restrictions. Forward stepwise logistic
      regression analysis was performed to control for confounders. RESULTS: A total of
      2528 patients were included, 24% were women. Mean age 63.4+/-13.4 years; 16.7%
      presented atypical clinical symptoms. Initial complications: ventricular
      fibrillation (VF) 8.4%, severe bradycardia 5.8%, third-degree atrial-ventricular
      (AV) block 2.4% and hypotension 13.5%. Fifty-two (2.1%) patients died before
      reaching hospital. Factors associated with prehospital mortality were female sex
      (OR 2.36, CI 1.28 to 4.33), atypical clinical picture (OR 2.31, CI 1.21 to 4.41),
      hypotension (OR 4.95, CI 2.60 to 9.20), LBBB (OR 4.29, CI 1.71 to 10.74),
      extensive infarction (ST elevation in >=5 leads) (OR 2.53, CI 1.28 to 5.01) and
      VF (OR 2.82, CI 1.38 to 5.78). CONCLUSIONS: A significant proportion of patients
      with STEMI present early complications in the prehospital setting, and some die
      before reaching hospital. Prehospital mortality was associated with female sex
      and atypical presentation, as pre-existing conditions, and hypotension, extensive
      infarction, LBBB and VF on emergency team attendance.

PMID- 25062683
TI  - Corticostriatal control of goal-directed action is impaired in schizophrenia.
AB  - BACKGROUND: Goal-directed actions depend on our capacity to integrate the
      anticipated consequences of an action with the value of those consequences, with
      the latter derived from direct experience or inferred from predictive stimuli.
      Schizophrenia is associated with poor goal-directed performance, but whether this
      reflects a deficit in experienced or predicted value or in integrating these
      values with action-outcome information is unknown, as is the locus of any
      associated neuropathology. METHODS: We assessed the contribution of these sources
      of value to goal-directed actions in people with schizophrenia (SZ) (n = 18) and
      healthy adults (n = 18). Participants learned to use specific actions to liberate
      snack foods from a vending machine. They also learned about the reward value of
      the foods, changes in reward value, and the relationship between various
      predictive stimuli and food delivery. We then evaluated the ability of subjects
      to use experienced or predicted value to guide goal-directed actions while
      undergoing functional magnetic resonance imaging. RESULTS: Acquisition and
      sensitivity to experienced changes in outcome value did not differ in SZ and
      healthy adults. The SZ were, however, deficient in their ability to integrate
      action-outcome learning with outcome values to guide choice, more so when actions
      were guided by experienced than by predicted values. These effects were
      differentially associated with reductions in activity in caudate and limbic
      structures, respectively. CONCLUSIONS: This novel assessment of goal-directed
      learning revealed dysfunction in corticostriatal control associated with a
      profound deficit in integrating changes in experienced value with the action
      outcome association in schizophrenia.

PMID- 25062686
TI  - Changes in attachment representations for young people in long-term therapeutic
      foster care.
AB  - This article reports on a 1-year follow-up study exploring changes in attachment
      security of children placed in long-term therapeutic foster care over three data
      collection time points. A group of eight children (age 14 to 17) were assessed
      over a period of 1 year using a modified version of the Separation Anxiety Test
      (SAT). Interviews were also conducted to explore the young people's and the
      carers' experiences of the placements and their personal perspectives of changes.
      The findings indicated some positive changes in the young people's attachment
      security over time, for example, a reduction in extreme reactions and a trust
      that adults could understand their feelings (PAE - parental accurate empathy).
      However, despite this PAE, the young people did not expect adults to enact this
      by offering them support, and this lack of expectation persisted over the 1-year
      period. Specific differences in relation to placement success were suggested in
      that young people for whom their placements broke down indicated more initial
      fearful and aggressive representations of adults. Overall, young people
      emphasised positive aspects of their placements as including being treated as
      adults, listened to and made to feel safe. 

PMID- 25062684
TI  - Decreased vesicular monoamine transporter type 2 availability in the striatum
      following chronic cocaine self-administration in nonhuman primates.
AB  - BACKGROUND: Consistent with postmortem data, in a recent positron emission
      tomography study, we demonstrated less [(11)C]-(+)-dihydrotetrabenazine
      ([(11)C]DTBZ) binding to striatal vesicular monoamine transporter type 2 (VMAT2)
      in cocaine abusers compared with control subjects. A major limitation of these
      between-group comparison human studies is their inability to establish a causal
      relationship between cocaine abuse and lower VMAT2. Furthermore, studies in
      rodents that evaluated VMAT2 binding before and after cocaine self-administration
      do not support a reduction in VMAT2. METHODS: To clarify these discrepant VMAT2
      findings and attribute VMAT2 reduction to cocaine abuse, we imaged four rhesus
      monkeys with [(11)C]DTBZ positron emission tomography before and after 16 months
      of cocaine self-administration. [(11)C]DTBZ binding potential in the striatum was
      derived using the simplified reference tissue method with the occipital cortex
      time activity curve as an input function. RESULTS: Chronic cocaine self
      administration led to a significant (25.8 +/- 7.8%) reduction in [(11)C]DTBZ
      binding potential. CONCLUSIONS: In contrast to the cocaine rodent investigations
      that do not support alterations in VMAT2, these results in nonhuman primates
      clearly demonstrated a reduction in VMAT2 binding following prolonged exposure to
      cocaine. Lower VMAT2 implies that fewer dopamine storage vesicles are available
      in the presynaptic terminals for release, a likely factor contributing to
      decreased dopamine transmission in cocaine dependence. Future studies should
      attempt to clarify the clinical significance of lower VMAT2 in cocaine abusers,
      for example, its relationship to relapse and vulnerability to mood disorders.

PMID- 25062687
TI  - "Why are you here?" Seeking children's accounts of their presentation to Child
      and Adolescent Mental Health Service (CAMHS).
AB  - The area of child mental health has a developing evidence base, with much of this
      focused on outcomes and a growing recognition for the value of process research.
      Despite this growth, however, there has still been little work conducted on first
      assessments in spite of their importance in establishing therapeutic rapport and
      engagement with services. We explore naturally occurring first assessments in a
      Child and Adolescent Mental Health Service (CAMHS) to explore the beliefs that
      children hold regarding their reasons for attendance and the implications this
      has for the trajectory of the appointment and later engagement with
      interventions. It was found that when children were asked for their reasons they
      either offered explanations using diagnostic labels or used lay descriptions, or
      they claimed to not know the reasons for attending the assessment. This has
      broader implications regarding the nature and type of information children may
      require in preparing them for service visits. 

PMID- 25062688
TI  - Potentiated Hsp104 variants suppress toxicity of diverse neurodegenerative
      disease-linked proteins.
AB  - Protein misfolding is implicated in numerous lethal neurodegenerative disorders,
      including amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD). There
      are no therapies that reverse these protein-misfolding events. We aim to apply
      Hsp104, a hexameric AAA+ protein from yeast, to target misfolded conformers for
      reactivation. Hsp104 solubilizes disordered aggregates and amyloid, but has
      limited activity against human neurodegenerative disease proteins. Thus, we have
      previously engineered potentiated Hsp104 variants that suppress aggregation,
      proteotoxicity and restore proper protein localization of ALS and PD proteins in
      Saccharomyces cerevisiae, and mitigate neurodegeneration in an animal PD model.
      Here, we establish that potentiated Hsp104 variants possess broad substrate
      specificity and, in yeast, suppress toxicity and aggregation induced by wild-type
      TDP-43, FUS and alpha-synuclein, as well as missense mutant versions of these
      proteins that cause neurodegenerative disease. Potentiated Hsp104 variants also
      rescue toxicity and aggregation of TAF15 but not EWSR1, two RNA-binding proteins
      with a prion-like domain that are connected with the development of ALS and
      frontotemporal dementia. Thus, potentiated Hsp104 variants are not entirely non
      specific. Indeed, they do not unfold just any natively folded protein. Rather,
      potentiated Hsp104 variants are finely tuned to unfold proteins bearing short
      unstructured tracts that are not recognized by wild-type Hsp104. Our studies
      establish the broad utility of potentiated Hsp104 variants. 

PMID- 25062689
TI  - Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in
      vivo in mice.
AB  - Neonatal jaundice is caused by high levels of unconjugated bilirubin. It is
      usually a temporary condition caused by delayed induction of UGT1A1, which
      conjugates bilirubin in the liver. To reduce bilirubin levels, affected babies
      are exposed to phototherapy (PT), which converts toxic bilirubin into water
      soluble photoisomers that are readily excreted out. However, in some cases
      uncontrolled hyperbilirubinemia leads to neurotoxicity. To study the mechanisms
      of bilirubin-induced neurological damage (BIND) in vivo, we generated a mouse
      model lacking the Ugt1a1 protein and, consequently, mutant mice developed
      jaundice as early as 36 hours after birth. The mutation was transferred into two
      genetic backgrounds (C57BL/6 and FVB/NJ). We exposed mutant mice to PT for
      different periods and analyzed the resulting phenotypes from the molecular,
      histological and behavioral points of view. Severity of BIND was associated with
      genetic background, with 50% survival of C57BL/6-Ugt1(-/-) mutant mice at
      postnatal day 5 (P5), and of FVB/NJ-Ugt1(-/-) mice at P11. Life-long exposure to
      PT prevented cerebellar architecture alterations and rescued neuronal damage in
      FVB/NJ-Ugt1(-/-) but not in C57BL/6-Ugt1(-/-) mice. Survival of FVB/NJ-Ugt1(-/-)
      mice was directly related to the extent of PT treatment. PT treatment of FVB/NJ
      Ugt1(-/-) mice from P0 to P8 did not prevent bilirubin-induced reduction in
      dendritic arborization and spine density of Purkinje cells. Moreover, PT
      treatment from P8 to P20 did not rescue BIND accumulated up to P8. However, PT
      treatment administered in the time-window P0-P15 was sufficient to obtain full
      rescue of cerebellar damage and motor impairment in FVB/NJ-Ugt1(-/-) mice. The
      possibility to modulate the severity of the phenotype by PT makes FVB/NJ-Ugt1(-/
      ) mice an excellent and versatile model to study bilirubin neurotoxicity, the
      role of modifier genes, alternative therapies and cerebellar development during
      high bilirubin conditions. 

PMID- 25062690
TI  - ERG-APLNR axis controls pulmonary venule endothelial proliferation in pulmonary
      veno-occlusive disease.
AB  - BACKGROUND: Pulmonary veno-occlusive disease is caused by excessive cell
      proliferation and fibrosis, which obliterate the lumen of pulmonary venules,
      leading to pulmonary hypertension, right ventricular failure, and death. This
      condition has no effective treatment and a 5-year survival of <5%. Understanding
      the mechanism of this disease and designing effective therapies are urgently
      needed. METHODS AND RESULTS: We show that mice with homozygous deletion of the
      Ets transcription factor Erg die between embryonic day 16.5 and 3 months of age
      as a result of pulmonary veno-occlusive disease, capillary hemorrhage, and
      pancytopenia. We demonstrate that Erg binds to and serves as a transcriptional
      activator of the G-protein-coupled receptor gene Aplnr, the expression of which
      is uniquely specific for venous endothelium and that knockout of either Erg or
      Aplnr results in pulmonary venule-specific endothelial proliferation in vitro. We
      show that mice with either homozygous-global or endothelium-directed deletion of
      Aplnr manifest pulmonary veno-occlusive disease and right heart failure,
      detectable at 8 months of age. Levels of pulmonary ERG and APLNR in patients with
      pulmonary veno-occlusive disease undergoing lung transplantation were
      significantly lower than those of control subjects. CONCLUSIONS: Our results
      suggest that ERG and APLNR are essential for endothelial homeostasis in venules
      in the lung and that perturbation in ERG-APLNR signaling is crucial for the
      development of pulmonary veno-occlusive disease. We identify this pathway as a
      potential therapeutic target for the treatment of this incurable disease.

PMID- 25062691
TI  - Acute rupture of chordae tendineae of the mitral valve in infants: a nationwide
      survey in Japan exploring a new syndrome.
AB  - BACKGROUND: Recently, infant cases of acute heart failure attributable to rupture
      of the mitral chordae tendineae have been reported. However, little is known
      about the pathogenesis and clinical course of this condition. METHODS AND
      RESULTS: Ninety-five children with rupture of mitral chordae tendineae were
      identified in nationwide surveys of Japan diagnosed from 1995 to 2013. The
      clinical manifestations, management strategies, and prognosis were investigated.
      Eighty-one (85%) patients were between 4 and 6 months (median, 5 months) of age.
      In 63 (66%) patients, rupture occurred during the spring or summer. The
      underlying conditions before rupture included Kawasaki disease (10 cases),
      maternally derived anti-SSA antibodies (2 cases), and infective endocarditis (1
      case). Surgery was performed in 80 patients (94 operations), and the final
      operations included plasty of mitral chordae in 52 cases and mechanical valve
      replacement in 26 cases. The histopathologic examinations of the mitral valves
      and chordae (n=28) revealed inflammatory reactions with predominant mononuclear
      cell infiltration in 18 cases (64%) and increased fibrous and myxoid tissue in 11
      cases (39%), suggesting that nonbacterial infectious or autoimmune endocarditis
      and myxoid changes are involved in the pathogenesis. Eight patients (8.4%) died
      before (n=6) and shortly after (n=2) the operation, and significant neurological
      complications persisted in 10 cases (11%). CONCLUSIONS: Acute heart failure
      attributable to rupture of the mitral chordae tendineae in infants is a unique
      disease resulting from diverse causes. This condition should be recognized as a
      significant cardiovascular disorder that may cause sudden onset of cardiogenic
      shock and death in infants.

PMID- 25062692
TI  - Direct evidence for a magnetic f-electron-mediated pairing mechanism of heavy
      fermion superconductivity in CeCoIn5.
AB  - To identify the microscopic mechanism of heavy-fermion Cooper pairing is an
      unresolved challenge in quantum matter studies; it may also relate closely to
      finding the pairing mechanism of high-temperature superconductivity. Magnetically
      mediated Cooper pairing has long been the conjectured basis of heavy-fermion
      superconductivity but no direct verification of this hypothesis was achievable.
      Here, we use a novel approach based on precision measurements of the heavy
      fermion band structure using quasiparticle interference imaging to reveal
      quantitatively the momentum space (k-space) structure of the f-electron magnetic
      interactions of CeCoIn5. Then, by solving the superconducting gap equations on
      the two heavy-fermion bands Ek(alpha,beta) with these magnetic interactions as
      mediators of the Cooper pairing, we derive a series of quantitative predictions
      about the superconductive state. The agreement found between these diverse
      predictions and the measured characteristics of superconducting CeCoIn5 then
      provides direct evidence that the heavy-fermion Cooper pairing is indeed mediated
      by f-electron magnetism.

PMID- 25062693
TI  - Native structure of a type IV secretion system core complex essential for
      Legionella pathogenesis.
AB  - Bacterial type IV secretion systems are evolutionarily related to conjugation
      systems and play a pivotal role in infection by delivering numerous virulence
      factors into host cells. Using transmission electron microscopy, we report the
      native molecular structure of the core complex of the Dot/Icm type IV secretion
      system encoded by Legionella pneumophila, an intracellular human pathogen. The
      biochemically isolated core complex, composed of at least five proteins--DotC,
      DotD, DotF, DotG, and DotH--has a ring-shaped structure. Intriguingly,
      morphologically distinct premature complexes are formed in the absence of DotG or
      DotF. Our data suggest that DotG forms a central channel spanning inner and outer
      membranes. DotF, a component dispensable for type IV secretion, plays a role in
      efficient embedment of DotG into the functional core complex. These results
      highlight a common scheme for the biogenesis of transport machinery.

PMID- 25062694
TI  - Neural bases of imitation and pantomime in acute stroke patients: distinct
      streams for praxis.
AB  - Apraxia is a cognitive disorder of skilled movements that characteristically
      affects the ability to imitate meaningless gestures, or to pantomime the use of
      tools. Despite substantial research, the neural underpinnings of imitation and
      pantomime have remained debated. An influential model states that higher motor
      functions are supported by different processing streams. A dorso-dorsal stream
      may mediate movements based on physical object properties, like reaching or
      grasping, whereas skilled tool use or pantomime rely on action representations
      stored within a ventro-dorsal stream. However, given variable results of past
      studies, the role of the two streams for imitation of meaningless gestures has
      remained uncertain, and the importance of the ventro-dorsal stream for pantomime
      of tool use has been questioned. To clarify the involvement of ventral and dorsal
      streams in imitation and pantomime, we performed voxel-based lesion-symptom
      mapping in a sample of 96 consecutive left-hemisphere stroke patients (mean age
      +/- SD, 63.4 +/- 14.8 years, 56 male). Patients were examined in the acute phase
      after ischaemic stroke (after a mean of 5.3, maximum 10 days) to avoid
      interference of brain reorganization with a reliable lesion-symptom mapping as
      best as possible. Patients were asked to imitate 20 meaningless hand and finger
      postures, and to pantomime the use of 14 common tools depicted as line drawings.
      Following the distinction between movement engrams and action semantics,
      pantomime errors were characterized as either movement or content errors,
      respectively. Whereas movement errors referred to incorrect spatio-temporal
      features of overall recognizable movements, content errors reflected an inability
      to associate tools with their prototypical actions. Both imitation and pantomime
      deficits were associated with lesions within the lateral occipitotemporal cortex,
      posterior inferior parietal lobule, posterior intraparietal sulcus and superior
      parietal lobule. However, the areas specifically related to the dorso-dorsal
      stream, i.e. posterior intraparietal sulcus and superior parietal lobule, were
      more strongly associated with imitation. Conversely, in contrast to imitation,
      pantomime deficits were associated with ventro-dorsal regions such as the
      supramarginal gyrus, as well as brain structures counted to the ventral stream,
      such as the extreme capsule. Ventral stream involvement was especially clear for
      content errors which were related to anterior temporal damage. However, movement
      errors were not consistently associated with a specific lesion location. In
      summary, our results indicate that imitation mainly relies on the dorso-dorsal
      stream for visuo-motor conversion and on-line movement control. Conversely,
      pantomime additionally requires ventro-dorsal and ventral streams for access to
      stored action engrams and retrieval of tool-action relationships.

PMID- 25062696
TI  - Hippocampal Lewy pathology and cholinergic dysfunction are associated with
      dementia in Parkinson's disease.
AB  - The neuropathological substrate of dementia in patients with Parkinson's disease
      is still under debate, particularly in patients with insufficient alternate
      neuropathology for other degenerative dementias. In patients with pure Lewy body
      Parkinson's disease, previous post-mortem studies have shown that dopaminergic
      and cholinergic regulatory projection systems degenerate, but the exact pathways
      that may explain the development of dementia in patients with Parkinson's disease
      remain unclear. Studies in rodents suggest that both the mesocorticolimbic
      dopaminergic and septohippocampal cholinergic pathways may functionally interact
      to regulate certain aspects of cognition, however, whether such an interaction
      occurs in humans is still poorly understood. In this study, we performed
      stereological analyses of the A9 and A10 dopaminergic neurons and Ch1, Ch2 and
      Ch4 cholinergic neurons located in the basal forebrain, along with an assessment
      of alpha-synuclein pathology in these regions and in the hippocampus of six
      demented and five non-demented patients with Parkinson's disease and five age
      matched control individuals with no signs of neurological disease. Moreover, we
      measured choline acetyltransferase activity in the hippocampus and frontal cortex
      of eight demented and eight non-demented patients with Parkinson's disease, as
      well as in the same areas of eight age-matched controls. All patients with
      Parkinson's disease exhibited a similar 80-85% loss of pigmented A9 dopaminergic
      neurons, whereas patients with Parkinson's disease dementia presented an
      additional loss in the lateral part of A10 dopaminergic neurons as well as Ch4
      nucleus basalis neurons. In contrast, medial A10 dopaminergic neurons and Ch1 and
      Ch2 cholinergic septal neurons were largely spared. Despite variable Ch4 cell
      loss, cortical but not hippocampal cholinergic activity was consistently reduced
      in all patients with Parkinson's disease, suggesting significant dysfunction in
      cortical cholinergic pathways before frank neuronal degeneration. Patients with
      Parkinson's disease dementia were differentiated by a significant reduction in
      hippocampal cholinergic activity, by a significant loss of non-pigmented lateral
      A10 dopaminergic neurons and Ch4 cholinergic neurons (30 and 55% cell loss,
      respectively, compared with neuronal preservation in control subjects), and by an
      increase in the severity of alpha-synuclein pathology in the basal forebrain and
      hippocampus. Overall, these results point to increasing alpha-synuclein
      deposition and hippocampal dysfunction in a setting of more widespread
      degeneration of cortical dopaminergic and cholinergic pathways as contributing to
      the dementia occurring in patients with pure Parkinson's disease. Furthermore,
      our findings support the concept that alpha-synuclein deposition is associated
      with significant neuronal dysfunction in the absence of frank neuronal loss in
      Parkinson's disease.

PMID- 25062695
TI  - Sialyllactose ameliorates myopathic phenotypes in symptomatic GNE myopathy model
      mice.
AB  - Patients with GNE myopathy, a progressive and debilitating disease caused by a
      genetic defect in sialic acid biosynthesis, rely on supportive care and
      eventually become wheelchair-bound. To elucidate whether GNE myopathy is
      treatable at a progressive stage of the disease, we examined the efficacy of
      sialic acid supplementation on symptomatic old GNE myopathy mice that have
      ongoing, active muscle degeneration. We examined the therapeutic effect of a less
      metabolized sialic acid compound (6'-sialyllactose) or free sialic acid (N
      acetylneuraminic acid) by oral, continuous administration to 50-week-old GNE
      myopathy mice for 30 weeks. To evaluate effects on their motor performance in
      living mice, spontaneous locomotion activity on a running wheel was measured
      chronologically at 50, 65, 72 and 80 weeks of age. The size, force production,
      and pathology of isolated gastrocnemius muscle were analysed at the end point.
      Sialic acid level in skeletal muscle was also measured. Spontaneous locomotion
      activity was recovered in 6'-sialyllactose-treated mice, while NeuAc-treated mice
      slowed the disease progression. Treatment with 6'-sialyllactose led to marked
      restoration of hyposialylation in muscle and consequently to robust improvement
      in the muscle size, contractile parameters, and pathology as compared to NeuAc.
      This is due to the fact that 6'-sialyllactose is longer working as it is further
      metabolized to free sialic acid after initial absorption. 6'-sialyllactose
      ameliorated muscle atrophy and degeneration in symptomatic GNE myopathy mice. Our
      results provide evidence that GNE myopathy can be treated even at a progressive
      stage and 6'-sialyllactose has more remarkable advantage than free sialic acid,
      providing a conceptual proof for clinical use in patients.

PMID- 25062697
TI  - Salinispirillum marinum gen. nov., sp. nov., a haloalkaliphilic bacterium in the
      family 'Saccharospirillaceae'.
AB  - A novel Gram-staining-negative, motile, non-pigmented, facultatively anaerobic,
      spirillum-shaped, halophilic and alkaliphilic bacterium, designated strain
      GCWy1(T), was isolated from water of the coastal-marine wetland Gomishan in Iran.
      The strain was able to grow at NaCl concentrations of 1-10% (w/v) and optimal
      growth was achieved at 3% (w/v). The optimum pH and temperature for growth were
      pH 8.5 and 30  degrees C, while the strain was able to grow at pH 7.5-10 and 4-40
      degrees C. Phylogenetic analysis based on the comparison of the 16S rRNA gene
      sequence placed the isolate within the class Gammaproteobacteria as a separate
      deep branch, with 92.1% or lower sequence similarity to representatives of the
      genera Saccharospirillum and Reinekea and less than 91.0% sequence similarity
      with other remotely related genera. The major cellular fatty acids of the isolate
      were C(18 : 1)omega7c, C(16:0) and C(17 : 0), and the major components of its
      polar lipid profile were diphosphatidylglycerol, phosphatidylglycerol and
      phosphatidylethanolamine. The cells of strain GCWy1(T) contained the isoprenoid
      quinones Q-9 and Q-8 (81% and 2%, respectively). The G+C content of the genomic
      DNA of this strain was 52.3 mol%. On the basis of 16S rRNA gene sequence analysis
      in combination with chemotaxonomic and phenotypic data, strain GCWy1(T)
      represents a novel species in a new genus in the family 'Saccharospirillaceae',
      order Oceanospirillales, for which the name Salinispirillum marinum gen. nov.,
      sp. nov. is proposed. The type strain of the type species is GCWy1(T) ( = IBRC-M
      10765(T) =CECT 8342(T)).

PMID- 25062698
TI  - Aquibacillus halophilus gen. nov., sp. nov., a moderately halophilic bacterium
      from a hypersaline lake, and reclassification of Virgibacillus koreensis as
      Aquibacillus koreensis comb. nov. and Virgibacillus albus as Aquibacillus albus
      comb. nov.
AB  - A novel Gram-stain-positive, moderately halophilic bacterium, designated strain
      B6B(T), was isolated from the water of an Iranian hypersaline lake, Aran-Bidgol,
      and characterized taxonomically using a polyphasic approach. Cells of strain
      B6B(T) were rod-shaped, motile and produced ellipsoidal endospores in terminal
      positions in non-swollen sporangia. Strain B6B(T) was a strictly aerobic
      bacterium and catalase- and oxidase-positive. The strain was able to grow at NaCl
      concentrations of 0.5-20.0% (w/v), with optimum growth occurring at 10.0% (w/v)
      NaCl. The optimum temperature and pH for growth were 35  degrees C and pH 7.0. On
      the basis of 16S rRNA gene sequence analysis, strain B6B(T) was shown to belong
      to the phylum Firmicutes and its closest phylogenetic similarities were with the
      species Virgibacillus koreensis BH30097(T) (97.5%), Virgibacillus albus YIM
      93624(T) (97.4%), Sediminibacillus halophilus EN8d(T) (96.8%), Sediminibacillus
      albus NHBX5(T) (96.6%), Virgibacillus carmonensis LMG 20964(T) (96.3%) and
      Paraliobacillus quinghaiensis YIM-C158(T) (96.0%), respectively. Phylogenetic
      analysis revealed that strain B6B(T), along with V. koreensis BH30097(T) and V.
      albus YIM 93624(T), clustered in a separate clade in the family Bacillaceae. The
      DNA G+C content of the novel isolate was 35.8 mol%. DNA-DNA hybridization
      experiments revealed low levels of relatedness between strain B6B(T)and V.
      koreensis BH30097(T) (13%) and V. albus YIM 93624(T) (33%). The major cellular
      fatty acid of strain B6B(T) was anteiso-C15 : 0 (75.1%) and its polar lipid
      pattern consisted of phosphatidylglycerol, diphosphatidylglycerol, an unknown
      phospholipid and an unknown glycolipid. The isoprenoid quinones were MK-7 (90%)
      and MK-6 (3%). The peptidoglycan contained meso-diaminopimelic acid as the
      diagnostic diamino acid. All of these features support the placement of isolate
      B6B(T) within the phylum Firmicutes. It is closely related to V. koreensis and V.
      albus, but with features that clearly distinguish it from species of the genus
      Virgibacillus or of other related genera. On the basis of the polyphasic evidence
      derived in this study, we propose that strain B6B(T) be placed within a new
      genus, as Aquibacillus halophilus gen. nov., sp. nov., with B6B(T) as the type
      strain ( =IBRC-M 10775(T) =KCTC 13828(T)). We also propose that V. koreensis and
      V. albus should be transferred to this new genus and be named Aquibacillus
      koreensis comb. nov. and Aquibacillus albus comb. nov., respectively. The type
      strain of Aquibacillus koreensis comb. nov. is BH30097(T) ( =KCTC 3823(T) =IBRC-M
      10657(T) =JCM 12387(T)) and the type strain of Aquibacillus albus comb. nov. is
      YIM 93624(T) ( =DSM 23711(T) =IBRC-M 10798(T) =JCM 17364(T)).

PMID- 25062699
TI  - Pseudomonas salegens sp. nov., a halophilic member of the genus Pseudomonas
      isolated from a wetland.
AB  - A novel Gram-stain-negative, aerobic, non-endospore-forming, non-pigmented, rod
      shaped, slightly halophilic bacterium, designated GBPy5(T), was isolated from
      aquatic plants of the Gomishan wetland, Iran. Cells of strain GBPy5(T) were
      motile. Growth occurred with between 1 and 10% (w/v) NaCl and the isolate grew
      optimally with 3% (w/v) NaCl. The optimum pH and temperature for growth of the
      strain were pH 8.0 and 30  degrees C, respectively, while it was able to grow
      over a pH range of 6.5-9.0 and a temperature range of 4-35  degrees C.
      Phylogenetic analysis, based on 16S rRNA gene sequences, revealed that strain
      GBPy5(T) is a member of the genus Pseudomonas forming a monophyletic branch. The
      novel strain exhibited 16S rRNA gene sequence similarity of 95.4% with type
      strains of Pseudomonas guariconensis PCAVU11(T) and Pseudomonas sabulinigri
      J64(T), respectively. The major cellular fatty acids of the isolate were
      C18:1omega7c (37.8%), C16:0 (14.9%), C16:1omega7c (12.9%), C12:0 3-OH (7.1%) and
      C12:0 (7.0%). The polar lipid pattern of strain GBPy5(T) comprised
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and one
      phospholipid. Ubiquinone 9 (Q-9) was the predominant lipoquinone. The G+C content
      of the genomic DNA of strain GBPy5(T) was 59.2 mol%. On the basis of the
      phenotypic and phylogenetic data, strain GBPY5(T) represents a novel species of
      the genus Pseudomonas, for which the name Pseudomonas salegens sp. nov. is
      proposed. The type strain is GBPy5(T) ( = IBRC-M 10762(T) = CECT 8338(T)).

PMID- 25062700
TI  - Transnationalism and Hypertension Self-Management Among Haitian Immigrants.
AB  - PURPOSE: Transnationalism--maintenance of transborder activities--has important
      implications for the health status of contemporary immigrants. Yet little is
      known about how such interconnectivity interacts with health. DESIGN: In this
      critical ethnography study, 31 Haitian immigrants discussed the influences of
      transnationalism on their hypertension management. Transcripts of the
      semistructured individual interviews were analyzed and coded with the assistance
      of the Atlas.ti 6 software. FINDINGS: Two major themes emerged: social support
      and financial obligation, both framed within the obligation to send monetary
      remittances. A duality emerged where social support facilitated hypertension self
      management but consequently represented a financial burden. DISCUSSION AND
      IMPLICATIONS: The study evidenced that transnationalism, although positively
      influencing immigrants' psychosocial well-being can negatively affect their
      experience with disease management. Health providers are urged to account for
      this transnationalism-disease management interaction when caring for this
      immigrant group. Future studies are needed to explore this phenomenon among other
      immigrant populations.

PMID- 25062701
TI  - Severe and isolated headache associated with hypertension as unique clinical
      presentation of posterior reversible encephalopathy syndrome.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome is a potentially
      reversible clinicoradiologic syndrome characterized by headache, mental
      confusion, visual disturbances and seizures associated with posterior cerebral
      lesions on radiological imaging. Prompt treatment of this condition is mandatory
      to avoid severe irreversible complications. CASE PRESENTATION: We report a 9-year
      old boy with arterial hypertension and headache as unique clinical presentation
      of posterior reversible encephalopathy syndrome. CONCLUSIONS: Severe and isolated
      headache associated with arterial hypertension can be the unique clinical
      presentation of posterior reversible encephalopathy syndrome. This syndrome must
      be considered even in absence of all typical symptoms to prevent the progression
      of a potentially life threatening condition.

PMID- 25062702
TI  - An inverse relationship between allelopathic activity and salt tolerance in
      suspension cultures of three mangrove species, Sonneratia alba, S. caseolaris and
      S. ovata: development of a bioassay method for allelopathy, the protoplast co
      culture method.
AB  - A bioassay method for allelopathy, the 'protoplast co-culture method' was
      developed to study the relationship between salt tolerance and allelopathy of
      three mangrove species, Sonneratia alba, S. caseolaris, and S. ovata. Plants of
      S. alba grow in the seaward-side high salinity region and plants of the latter
      two species grow in upstream-side regions of a mangrove forest, respectively.
      Effects of five sea salts (NaCl, KCl, MgCl2, MgSO4 and CaCl2) on the growth of
      the suspension cells of the latter two species were first investigated by a small
      scale method using 24-well culture plates. S. ovata cells showed higher tolerance
      than S. caseolaris cells to NaCl and other salts, but were not as halophilic as
      S. alba cells. Protoplasts isolated from suspension cells were co-cultured with
      lettuce protoplasts in Murashige and Skoog's (MS) basal medium containing 1 MUM
      2,4-dichlorophenoxyacetic acid, 0.1 MUM benzyladenine, 3% sucrose and 0.6-0.8 M
      osmoticum. S. caseolaris protoplasts had a higher inhibitory effect on lettuce
      protoplast cell divisions than S. alba protoplasts at any lettuce protoplast
      density, and the effect of S. ovata was intermediate between the two. These
      results were similar to those obtained from a different in vitro bioassay method
      for allelopathy, the 'sandwich method' with dried leaves. The inverse
      relationship between allelopathic activity and salt tolerance in suspension cells
      of Sonneratia mangroves is discussed.

PMID- 25062703
TI  - What sports activity levels are achieved in patients with modular tumor
      endoprostheses of osteosarcoma about the knee?
AB  - BACKGROUND: Advances in multimodal treatment have improved survival of patients
      with nonmetastatic osteosarcoma. At the same time, implant design has improved
      the outcomes of limb salvage with modular endoprostheses. However, little is
      known about sports activity in long-term survivors with osteosarcoma.
      QUESTIONS/PURPOSES: We wanted to evaluate (1) sports activity levels in long-term
      survivors of osteosarcoma about the knee who received a modular tumor
      endoprosthesis; (2) to determine if activity level changed over time from initial
      reconstruction or (3) was predicted from sports activity level before diagnosis;
      and (4) if complications that occurred affected sports or contributed to
      prosthetic failures. METHODS: Between 1995 and 2005, we treated 120 patients for
      osteosarcoma about the knee with resection and modular endoprosthetic
      reconstruction; of those, 25 (21%) have died, six (5%) had an amputation, 39
      (32%) did not speak German and so were ineligible, and 14 (12%) were either lost
      to followup or refused to participate, leaving 27 patients (14 females, 13 males;
      median age 19 years [range, 12-60 years); average followup 11 +/- 4 years) (54%
      of the living, German-speaking cohort) for this analysis. Tumors were located in
      the distal femur (n = 16) and the proximal tibia (n = 11). Sports participation
      as well as the UCLA Activity Score and the modified Weighted Activity Score were
      assessed retrospectively. Moreover, postoperative complications were evaluated.
      RESULTS: Before the diagnosis of osteosarcoma and 1, 3, and 5 years and at the
      latest followup, respectively, after their reconstructions, 24 (89%), nine (33%),
      20 (74%), and 24 patients (89%) were able to perform sports activities. There was
      a reduction in high-impact activities. Those patients with followup longer than 5
      years had no changes in sports activity at their latest followup. Patients who
      had higher levels of sports activity levels before surgery generally had higher
      levels of activity at last followup (UCLA Activity Score: r = 0.62, p < 0.0005;
      modified Weighted Activity Score r = 0.49, p < 0.01). Fourteen patients (51%)
      underwent revision surgery. With the numbers available, complications had no
      effect on sports activity. No sports activity-related complications were found.
      CONCLUSIONS: Some long-term survivors of osteosarcoma can achieve high levels of
      sports activity. Preoperative activity levels seem to influence the postoperative
      activity levels. This information is important to give realistic expectations for
      long-term survivors of osteosarcoma of the knee. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 25062704
TI  - Infrapatellar saphenous neuralgia after TKA can be improved with ultrasound
      guided local treatments.
AB  - BACKGROUND: Current opinion suggests that in some patients, chronic pain after
      total knee arthroplasty (TKA) has a neuropathic origin. Injury to the
      infrapatellar branch of the saphenous nerve (IPSN) has been implicated as a cause
      of medial knee pain; however, local treatments for this condition remain
      controversial. QUESTIONS/PURPOSES: We sought to explore the efficacy of local
      treatment to the IPSN in patients with persistent medial knee pain after TKA.
      METHODS: In this retrospective series, 16 consecutive patients with persistent
      medial knee pain after primary or revision TKA were identified after other
      potential etiologies of knee pain were excluded. Using advanced ultrasound
      imaging to identify the IPSN, hydrodissection of the nerve from the adjacent
      interfascial planes was performed followed by corticosteroid injection (local
      treatment). In two patients, radiofrequency ablation of the IPSN was subsequently
      performed for recurrent symptoms. The outcome measure of this study was patient
      reported relief of medial knee pain based on a visual analog scale (VAS) score of
      0 to 10 either at rest or with activity, whichever resulted in more pain for the
      patient. Followup was at a minimum of 6 months (median, 9 months; range, 6-12
      months). Before the procedure, the median highest VAS pain score, either at rest
      or with activity, was 8 of 10 (range, 6-10). RESULTS: Local injections to the
      infrapatellar saphenous nerve (one or two injections) improved medial pain after
      TKA to a VAS score of 0 or 1 in nine of our 16 patients. Three patients reported
      pain improvement to VAS levels of 3 to 4. Of the remaining four patients, two did
      not have improvement with VAS scores of 8, and two underwent subsequent
      radiofrequency ablation of the IPSN with resolution of pain in one patient.
      CONCLUSIONS: In summary, we believe injury to the IPSN may be an underappreciated
      cause of persistent medial pain after TKA. We report favorable preliminary
      results with local treatment to the nerve in nine of our 16 patients, suggesting
      that the neuritis is a reversible process in some patients; however, because of
      the possibility of a placebo effect, we believe this treatment modality should be
      tested in a randomized, placebo-controlled trial. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 25062705
TI  - Haste makes waste, but lack of urgency is opportunity lost.

PMID- 25062706
TI  - Money and morals: ending clinical trials for financial reasons.
AB  - Too often, biopharmaceutical companies stop their clinical trials solely for
      financial reasons. In this chapter, we discuss this phenomenon against the
      backdrop of a 2011 decision by Geron Corporation to abandon its stem cell
      clinical trial for spinal cord injury (SCI), the preliminary results of which
      were released in May 2014. We argue that the resultant harms are widespread and
      are different in nature from the consequences of stopping trials for scientific
      or medical reasons. We examine the ethical and social effects that arise from
      such decisions and discuss them in light of ethical frameworks, including duties
      of individual stakeholders and corporate sponsors. We offer ways that sponsors
      and clinical sites can ensure that trials are responsibly started, and once
      started adequately protect the interests of participants. We conclude with
      recommendations that industry sponsors of clinical trials should adopt in order
      to advance a collective and patient-centered research ethic.

PMID- 25062707
TI  - The S28H mutation on mNeptune generates a brighter near-infrared monomeric
      fluorescent protein with improved quantum yield and pH-stability.
AB  - For living deep-tissue imaging, the optical window favorable for light
      penetration is in near-infrared wavelengths, which requires fluorescent proteins
      with emission spectra in the near-infrared region. Here, we report that a single
      mutant Ser28His of mNeptune with a near-infrared (>=650 nm) emission maxima of
      652 nm is found to improve the brightness, photostability, and pH stability when
      compared with its parental protein mNeptune, while it remains as a monomer,
      demonstrating that there is still plenty of room to improve the performance of
      the existing near infrared fluorescence proteins by directed evolution. 

PMID- 25062708
TI  - A novel member of lymphocyte-specific protein tyrosine kinase protein identified
      in lamprey, Lampetra japonica.

PMID- 25062709
TI  - Tear film inflammatory mediators in patients with keratoconus.
AB  - To determine the concentration of inflammatory mediators in the tear film of
      patients with keratoconus. Basal tears from patients with keratoconus and from
      normal controls were collected using a capillary tube. Patients with keratoconus
      were examined in a routine fashion, and keratometric readings were also taken
      from corneal topographic maps .The concentration of cytokines including
      Interleukin 6,10,1b and Interferon-gamma was measured by enzyme-linked
      immunoadsorbent assay. Seventy-two subjects were enrolled in the study including
      42 patients with keratoconus and 30 normals. Patients with keratoconus had
      significantly higher levels of Interlukin 6,1b and Interferon-gamma (17.49 +/-
      1.92 pg/ml), (8.58 +/- 1.15 pg/ml), and (33.33 +/- 7.57 pg/ml) compared with
      control subjects (13.81 +/- 1.71 pg/ml), (4.98 +/- 0.52 pg/ml), and (22.99 +/-
      4.68 pg/ml), (P = 0.0001, P = 0.0001, and P = 0.0001). But the level of
      Interlukin-10 in keratoconus patients was significantly lower (6.07 +/- 1.35
      pg/ml) than controls (8.99 +/- 0.70 pg/ml) (P = 0.0001). We realized that the
      proinflammatory markers (Interlukin-6,1-b and Interferon-gamma) are over
      expressed, whereas the anti-inflammatory marker (Interlukin-10) is under
      expressed, indicating that the pathogenesis of keratoconus may involve complex
      chronic inflammatory events. Additional future studies will reveal the exact
      molecular and biochemical mechanisms that are required to better manage the
      disease and halt its progression.

PMID- 25062710
TI  - 25-Gauge pars plana vitrectomy for ciliary block (malignant) glaucoma.
AB  - To evaluate the efficacy of 25-ga pars plana vitrectomy (PPV) and 25-ga PPV
      combined with phacoemulsification surgery for managing ciliary block (malignant)
      glaucoma. The medical records of 11 eyes, in nine consecutive patients with
      malignant glaucoma were retrospectively reviewed to determine the efficacy of 25
      ga PPV for alleviating this disease. All phakic eyes underwent
      phacoemulsification surgery during vitrectomy. Control of intraocular pressure
      (IOP), pre- and postoperative best-corrected visual acuity (BCVA), and
      development of intra- and postoperative complications were evaluated during
      follow-up. Malignant glaucoma was promptly resolved, and recurrence was not
      observed during a mean follow-up period of 12.7 +/- 3.2 (range 6-18) months. The
      mean IOP decreased from 35.9 +/- 2.9 mmHg, preoperatively, to 16.0 +/- 1.4 mmHg,
      measured at last visit (P = 0.013). Although IOP control was achieved in all eyes
      after surgery, two eyes required long-term topical antiglaucoma medication. The
      mean logarithm of the minimum angle of resolution BCVA improved from +0.69 +/-
      0.11, preoperatively, to +0.29 +/- 0.07, postoperatively (P = 0.027). No severe
      intraoperative complications were observed. Postoperative complications mostly
      occurred during the first week after surgery, including transient corneal edema
      and Descemet's membrane folds in three eyes, fibrotic exudation in 2, local iris
      posterior synechia in 1, and transient hypotony in 1, which were resolved
      spontaneously or with medication. The 25-ga PPV procedure seems to be safe and
      effective for treating malignant glaucoma. Combined vitrectomy with
      phacoemulsification surgery and a staged surgical approach may improve the
      success rate.

PMID- 25062711
TI  - Hepatocyte growth factor suppresses hypoxia/reoxygenation-induced XO activation
      in cardiac microvascular endothelial cells.
AB  - Hypoxia/reoxygenation (H/R) is one of the cellular stresses in pathological
      conditions, such as myocardial infarction, stroke and organ transplantation.
      Oxidative stress caused by reactive oxygen species (ROS) is a crucial element of
      H/R injury in vascular endothelial cells (ECs). Xanthine oxidase (XO) has been
      recognized to contribute to H/R injury. Of note, xanthine oxidoreductase is
      synthesized as xanthine dehydrogenase (XDH) and needs to be converted to XO to
      become a source of superoxide. Hepatocyte growth factor (HGF) has been found to
      protect ECs against H/R injury. The relation, however, between HGF and XO in ECs
      under H/R conditions remains to be determined. Primary cultured rat cardiac
      microvascular endothelial cells (CMECs) were exposed to 4 h of hypoxia and
      followed by 1 h of reoxygenation. Generation of ROS and cytosolic Ca2+
      concentration was measured by flow cytometry qualification of DCFHDA and fluo-3
      AM staining cells, respectively. XDH mRNA was qualified by qRT-PCR analysis. XO
      activity was determined by colorimetric assay and XO protein levels were
      determined by Western blot. Cell apoptosis was assessed by caspase-3 activity and
      Annexin V/PI staining. After H/R, cellular ROS production significantly
      increased. Both XO activity and XO protein increased after H/R. Cellular ROS
      elevation was inhibited by allopurinol (a potent XO inhibitor), indicting XO
      accounting for the generation of ROS after H/R. In addition, XDH mRNA increased
      after H/R, indicating a de novo XDH synthesis, which needs to be converted to XO
      to become a source of superoxide. Pretreatment of HGF inhibited the elevation of
      XO activity and XO protein level after H/R; however, HGF has no effect on the
      increase of XDH mRNA. We also find an increase of the cytosolic Ca2+ in CMECs
      after H/R. BAPTA-AM, a cell-permeable Ca2+ chelator, prevented the increase of XO
      activity and XO protein levels, implicating the elevated cytosolic Ca2+
      concentration involvement in XO conversion and XO activation. HGF inhibited the
      elevation of cytosolic Ca2+ concentration in CMECs after H/R. Furthermore, HGF
      ameliorated H/R-induced CMECs apoptosis. These findings suggest a novel mechanism
      whereby HGF inhibited XO-generated ROS production after H/R treatment. H/R
      induces a de novo synthesis of XDH, the XO precursor. In addition, H/R increases
      cytosolic Ca2+ concentration and promotes a Ca2+ -involved XO conversion and XO
      activation. HGF has no effect on the increase of XDH mRNA; however, HGF inhibited
      the elevation of XO protein level and XO activity after H/R in the post
      transcriptional level primarily by inhibiting the increase of cytosolic Ca2+
      concentration. HGF protects CMECs from H/R-induced apoptosis by inhibiting the
      elevation of XO protein level and XO activity.

PMID- 25062712
TI  - Differences in ward-to-cath lab systolic blood pressure predicts long-term
      adverse outcomes after drug-eluting stent implantation.
AB  - We sought to investigate the effect of ward-to-cath lab blood pressure (BP)
      differences on long-term clinical outcomes in patients undergoing percutaneous
      coronary intervention (PCI) with drug-eluting stent (DES). There are limited data
      available on the association between PCI with DES and BP differences on long-term
      clinical outcomes. This study enrolled 994 patients who underwent PCI with DES
      from March 2003 to August 2007. Resting BP was measured in a ward environment
      before transfer to the cardiac catheterization lab (cath lab), and again when the
      patient was laid down on the cath lab table. Patients were divided into two
      groups according to the difference in ward-to-cath lab systolic BP. Large
      difference group (n = 383) was defined as the absolute systolic difference of >20
      mmHg and small difference group (n = 424) as the absolute systolic difference of
      <=20 mmHg. The primary endpoints were all-cause mortality, cardiac death,
      nonfatal myocardial infarction and stroke. A total of 807 patients (mean age 60
      +/- 10 years, 522 males) received follow-up for 5.1 +/- 2.4 years. The rate of
      all-cause mortality was significantly higher in the large difference group
      compared to the small difference group (6.6 vs. 2.8 %; adjusted hazard ratio (HR)
      2.43; 95 % confidence interval (CI) 1.22-4.83; p = 0.012). There were higher
      cardiac deaths seen in the large difference group compared to the small
      difference group (3.9 vs. 1.4 %; adjusted HR 2.84; 95 % CI 1.1-7.31; p = 0.031).
      Stroke (2.4 vs. 1.2 %, p = 0.125) and TVR (3.7 vs. 1.7 %, p = 0.051) had higher
      trends in the large difference group compared to the small difference group. The
      composite of primary endpoints (all-cause mortality, cardiac death, nonfatal MI
      and stroke) occurred more frequently in the large difference group compared to
      the small difference group (10.0 vs. 6.4 %; adjusted HR 1.71; 95 % CI 1.04-2.81;
      p = 0.033). A difference in ward-to-cath lab systolic BP of >20 mmHg may
      contribute to increased adverse outcomes in the form of all-cause mortality and
      cardiac deaths in patients undergoing PCI with DES.

PMID- 25062713
TI  - Contribution of apolipoprotein A-I to the reduction in high-sensitivity C
      reactive protein levels by different statins: comparative study of pitavastatin
      and atorvastatin.
AB  - Recently, investigation may have focused on modification of apolipoprotein A-I
      (apoA-I) associated with anti-inflammatory effect for the potential prevention of
      cardiovascular events. The purpose of this study was to evaluate the effects of
      atorvastatin and pitavastatin on serum apoA-I levels and to investigate the role
      of apoA-I in the anti-inflammatory effect of statin. We conducted a 6-month,
      prospective, randomized, open-label study in which we assigned
      hypercholesterolemic patients to a pitavastatin group (n = 52; 2 mg/day) or an
      atorvastatin group (n = 52; 10 mg/day) to investigate the effects of these two
      statins on the serum apoA-I levels and serum high-sensitivity C-reactive protein
      (hs-CRP) levels. There were no significant differences between the two groups in
      the changes in the low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol (HDL-C), or hs-CRP levels, but the change in apoA-I in the
      pitavastatin group was significantly greater than in the atorvastatin group (5.3
      vs. 1.4 %; p = 0.0001). A stepwise regression analysis revealed that the percent
      change in (Delta) serum apoA-I level was an independent predictor of the Delta
      serum hs-CRP (standard correlation coefficient = -0.198; p = 0.047). However,
      there was a significant negative correlation between the Delta apoA-I levels and
      Delta hs-CRP levels in the pitavastatin group (r = -0.283, p = 0.042), but not
      the atorvastatin group (r = -0.133, p = 0.356). The results suggest that the
      contribution of apoA-I to the reduction in serum hs-CRP levels by these two
      statins may be different. A decrease in hs-CRP level accompanied by an increase
      in apoA-I level may be involved in the pleiotropic effects of pitavastatin.

PMID- 25062714
TI  - Age-associated alterations of cardiac structure and function in the female
      F344xBN rat heart.
AB  - The Fischer 344/NNiaHSD * Brown Norway/BiNia F1 (F344xBN) rat model exhibits an
      increased life span and fewer age-associated pathologies compared to commonly
      used Fischer 344 (F344). How aging may affect cardiac structure and function in
      these animals, has to our knowledge, not been investigated. Echocardiography was
      performed on female F344xBN rats at 6, 26, and 30 months of age using a Phillips
      5500 Echocardiography system. Before sacrifice, electrocardiograms were measured
      in the female F344xBN in order to determine heart rhythm interval changes. Aging
      was associated with an increase in heart to body weight ratio, cardiomyocyte
      cross-sectional area, posterior wall thickening, and left ventricle chamber
      dilatation. Aging was associated with slight evidence of diastolic dysfunction.
      Alterations in heart rhythm intervals were associated with alterations in the
      spatial distribution of connexin 43. The incidence of arrhythmias was not
      different with age; however, valvular dysfunction was increased. These data
      suggest that aging in the female F344xBN rat heart is associated with changes in
      cardiac structure as well as function. Further investigation regarding other
      parameters of cardiac biochemistry and function is needed to better understand
      the normal compensated cardiovascular aging process in the female F344xBN.

PMID- 25062715
TI  - Are overall adiposity and abdominal adiposity separate or redundant determinants
      of blood viscosity?
AB  - In line with recent literature showing that both general adiposity and abdominal
      adiposity are independently associated with the risk of death, we recently
      reported that body mass index (BMI) and waist-to hip ratio (WHR) were independent
      predictors of blood viscosity, related to different determinants of viscosity
      (for BMI: plasma viscosity and red cell aggregation; for WHR: hematocrit). Since
      this report was challenged by a study showing that abdominal adiposity (as
      measured with waist circumference WC and not WHR) is the only independent
      determinant of viscosity, we re-assessed on our previous database correlations
      among viscosity factors, BMI, WHR and WC. Blood viscosity was correlated to BMI
      (r = 0.155 p = 0.004), WHR (r = 0.364; p = 0.027) and WC (r = 0.094; p = 0.05).
      Hematocrit was correlated to WHR (r = 0.524) but neither to BMI (r =-0.021) nor
      waist circumference (r = 0.053). WC was correlated with plasma viscosity (r =
      0.154; p = 0.002) while WHR was not (r =-0.0102 NS). A stepwise regression
      analysis selected two determinants of whole blood viscosity at high shear rate:
      BMI (p = 0.0167) and WC (p = 0.0003) excluding WHR. Therefore, in this sample,
      abdominal fatness expressed by WC and whole body adiposity remain independent
      determinants of blood viscosity. WHR and WC have not the same meaning, WC
      measuring the size of abdominal fat while WHR measuring the shape of body
      distribution regardless the degree of fat excess. Interestingly, hematocrit is
      rather related to shape (even within a normal range of body size) than the extent
      of abdominal fatness, and is not related to whole body adiposity.

PMID- 25062716
TI  - Hemorheological parameters and their correlations in OXYS rats: a new model of
      hyperviscosity syndrome.
AB  - Rheohaemapheresis aims to normalize major rheological parameters and is used to
      treat patients with dry age-related macular degeneration (AMD). While effective,
      this approach is invasive and requires specially trained personnel. Therefore,
      the search for novel effective compounds with hemorheological properties that can
      be taken orally to treat AMD is justified. The use of a robust rodent model of
      AMD with high blood viscosity is crucial to test the efficacy of potential
      hemorheological drugs to treat this disease. The objective of this study was to
      investigate whether OXYS rats, generally used as an animal model of AMD, have
      hyperviscosity syndrome. The results of this study show that blood viscosity in
      OXYS rats at low (3-10 s -1) and high (45-300 s -1) shear rates were 14-20% and 7
      10% higher than in Wistar rats, while hematocrit and plasma viscosity were not
      different. Red blood cells (RBCs) in OXYS rats were more prone to aggregation as
      shown by 39% shorter half-time than in Wistar rats. RBCs were also more rigid in
      OXYS than in Wistar rats as shown by 21-33% lower index of elongation at the
      shear stress of 1-7 Pa. These data indicate that OXYS rats have hyperviscosity
      syndrome as the result of abnormal RBC deformability and aggregation. We propose
      to use OXYS rats as an animal model for preclinical studies to test compounds
      with hemorheological properties aimed to treat AMD.

PMID- 25062717
TI  - Association of erythrocyte deformability with red blood cell distribution width
      in metabolic diseases and thalassemia trait.
AB  - Increased red blood distribution width (RDW) in anemia is related to disturbances
      in the cellular surface/volume ratio, usually accompanied by morphological
      alterations, while it has been shown in inflammatory diseases that the activity
      of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently
      it has been reported that higher RDW is related with decreased erythrocyte
      deformability, and that it could be related with the association of RDW and
      increased risk of cardiovascular diseases. In order to analyze the influence of
      morphological alterations and proinflammatory status on the relationship between
      RDW and erythrocyte deformability, we analyzed erythrocyte deformability along
      with RDW and other hematological and biochemical parameters in 36 alpha
      thalassemia, 20 beta-thalassemia, 20 deltabeta-thalassemia trait carriers, 61
      metabolic syndrome patients and 76 morbidly obese patients. RDW correlated
      inversely with erythrocyte deformability in minor beta-thalassemia (r =-0.530, p
      <  0.05), and directly in both metabolic syndrome and morbidly obese patients
      (rho= 0.270, p <  0.05 and rho= 0.258, p <  0.05, respectively). Minor beta
      thalassemia is often accompanied by more marked cell-shaped perturbations than
      other thalassemia traits. This could be the reason for this negative association
      only in this setting. Higher anisocytosis seems to be associated with greater
      morphologic alterations (shape/volume), which reduce erythrocyte deformability.
      The proinflammatory profile in metabolic patients can be related to the positive
      association of RDW with erythrocyte deformability found in these patients.
      However, further research is needed to explain the mechanisms underlying this
      association. 

PMID- 25062718
TI  - [Acute coronary syndrome].

PMID- 25062719
TI  - Response to hydroxycarbamide in pediatric beta-thalassemia intermedia: 8 years'
      follow-up in Egypt.
AB  - Hydroxycarbamide (hydroxyurea or HU) has been shown to increase fetal hemoglobin
      (HbF) in patients with beta-thalassemia intermedia (TI). The reported effects of
      HU in increasing the total hemoglobin (Hb) have been inconsistent. Studies of
      long-term therapy with HU in pediatric TI are rather uncommon. A retrospective
      observational study was carried out to evaluate the clinical responses to HU in
      Egyptian patients with beta-TI. One hundred patients; children (n = 82, mean age
      9.9 +/- 4.1 years) and adults (n = 18) were studied for the mean Hb, HbF%, median
      serum ferritin, transfusion history, and splenic size before and after HU therapy
      (mean dose 20.0 +/- 4.2 mg/kg/day, range 10-29 mg/kg/day) over a follow-up period
      4 to 96 months (mean 35.4 +/- 19.2 months). Molecular studies were also done for
      group of patients (n = 42). The overall response rate to HU was 79 %; 46 % were
      minor responders (with a reduction in transfusion rate by 50 % or more and/or an
      increase in their total hemoglobin level by 1-2 g/dl) and 33 % major responders
      (becoming transfusion-free and/or having an increase in total hemoglobin level by
      >2 g/dl). Mean hemoglobin increased among responders from 6.9 +/- 0.9 g/dl to 8.3
      +/- 1.4 g/dl (p < 0.001). A significant rise in mean HbF (27.0 vs. 42.5 %; p <
      0.011) and a decrease in median serum ferritin (800 vs. 644 ng/ml; p < 0.001)
      were also observed among responders (n = 45). Transfusions stopped in 44 % of
      pretreatment frequently transfused responders (n = 11/25). Splenic size decreased
      in 37 % of patients (n = 30/81). The predominant beta-thalassemia mutation was 1
      6 (T > C) in 32/42 (76 %) of studied patients; 28/32 were responders. Bivariate
      analysis showed no predictors of response as regards sex, pediatric and adult
      age, splenic status, or genotype. Hydroxycarbamide is a good therapeutic modality
      in the management of pediatric as in adult TI patients. It can minimize the need
      for blood transfusion, concomitant iron overload, and blood-born viral
      transmission especially in developing countries like Egypt.

PMID- 25062720
TI  - Diagnostic value of bronchoscopy in patients with hematologic malignancy and
      pulmonary infiltrates.
AB  - Pulmonary infections are a major cause of morbidity and mortality in patients
      with hematologic malignancy. Bronchoscopy is at present still the traditional
      first investigation in immunosuppressed patients that have developed pulmonary
      infiltrates. There is limited data available on the validity of fiberoptic
      bronchoscopy (FOB) with bronchoalveolar lavage (BAL) to determine the etiology of
      pulmonary infiltrates with concurrent hematologic malignancy. We retrospectively
      analyzed the microbiological results of 206 bronchoscopic examinations and
      treatment changes used in 187 patients with hematologic malignancy and pulmonary
      infiltrates. Bacteria, fungi, and viruses were found in 85 (41.3 %), 49 (23.8 %),
      and 55 (28.6 %) of cases, respectively, and overall yield of bronchoscopy was
      65.0 %. We compared the microbiological findings with respect to neutropenia,
      hematopoietic stem cell transplantation (HSCT) status, and the type of
      malignancy. There were significantly more bacterial and viral infections detected
      in post-HSCT patients, and more viruses were detected in patients without
      neutropenia. Galactomannan (GM) was measured in 149 BAL samples. With a GM index
      threshold of >=0.5, the sensitivity, specificity, and positive and negative
      predictive values (PPV and NPV, respectively) of the BAL GM assay were 93.94 %,
      86.21 %, 65.96 %, and 98.04 %, respectively. Treatment was modified in 62 cases
      (30.1 %). There was no significant relationship of treatment modification with
      the underlying disease, HSCT, or neutropenia. Bronchoscopy with BAL is a valuable
      diagnostic tool to determine the etiology and appropriate treatment in patients
      with hematologic malignancy and pulmonary infiltrates. A BAL GM test is
      recommended when invasive pulmonary aspergillosis is suspected. 

PMID- 25062721
TI  - Paclitaxel, ifosfamide, and cisplatin (TIP) as salvage and consolidation
      chemotherapy for advanced germ cell tumor.
AB  - PURPOSE: The purpose of the study was to assess the efficacy of TIP as salvage
      chemotherapy for germ cell tumor (GCT) patients with relapsed disease or
      cisplatin (CDDP)-refractory disease and consolidation chemotherapy for patients
      who responded unfavorably to first-line chemotherapy. METHODS: Forty-three
      patients with advanced GCT were treated with TIP. Eleven with relapsed disease
      and five with CDDP-refractory disease received TIP as salvage chemotherapy. The
      remaining 27 received TIP as consolidation chemotherapy following initial
      induction chemotherapy. All patients received prophylactic granulocyte colony
      stimulating factor. RESULTS: In total, 116 cycles of TIP were administered with a
      median of three cycles (range 1-4 cycles) per patient. Before TIP, 33 patients
      showed elevated tumor marker and 23 patients (70%) achieved marker normalization
      with the chemotherapy. One of six (17%) patients with refractory disease and 5 of
      10 (50%) patients with relapsed disease achieved durable complete response (CR)
      after TIP with or without surgery. Eighteen of 27 (67%) patients receiving TIP as
      consolidation chemotherapy achieved durable CR. Five additional patients were
      given further chemotherapy and achieved durable CR. Grade 4 leukocytopenia and
      thrombocytopenia were observed in 91 and 42% of patients, respectively; all were
      managed with routine supportive care. Grade 2 and grade 3 sensory neuropathy was
      observed in 37 and 2% of patients, respectively. CONCLUSIONS: The TIP was
      effective for relapsed patients with favorable risk features and selected CDDP
      refractory GCT patients. Results of TIP as consolidation for patients with
      unfavorable response to the initial chemotherapy were also encouraging. The
      toxicities were mainly myelosuppression and sensory neuropathy.

PMID- 25062722
TI  - The XRCC1 Arg194Trp and Arg280His polymorphisms in head and neck cancer
      susceptibility: a meta-analysis.
AB  - The XRCC1 Arg194Trp and Arg280His polymorphisms are likely to be implicated with
      the development of head and neck cancer. However, studies of association have
      been inconsistent. This meta-analysis of the available literature was performed
      to make a more precise estimation of the risk associated with these
      polymorphisms. A comprehensive literature search was conducted to identify all
      case-control studies of the XRCC1 Arg194Trp and Arg280His polymorphisms in head
      and neck cancer. Summary odds ratios (ORs) with 95% confidence intervals (CIs)
      were used to assess the strength of association. A total of 20 eligible studies
      were selected for this meta-analysis, including 3,362 cases and 5,796 controls
      for the XRCC1 Arg194Trp polymorphism and 1,932 cases and 2,757 controls for the
      XRCC1 Arg280His polymorphism. Overall, no significant associations were found in
      all genetic models when the studies were pooled into the meta-analysis for the
      Arg194Trp and Arg280His polymorphisms. When stratified by ethnicity, significant
      associations were found for Arg194Trp polymorphism in CT vs CC (OR = 1.26, 95% CI
      = 1.05-1.52) and the recessive model (OR = 1.28, 95% CI = 1.07-1.53) in Asian
      population, and no significant associations were found in non-Asian population in
      all genetic models. This meta-analysis suggests that the XRCC1 Arg194Trp
      polymorphism is a risk factor for head and neck cancer in Asian populations.

PMID- 25062723
TI  - A novel FGF2 antagonist peptide P8 with potent antiproliferation activity.
AB  - Some fibroblast growth factors (FGFs) play a critical role in tumorigenesis and
      progression. Among them, FGF2 was highly expressed in some tumors, and
      antagonists binding to FGF2 can suppress the growth of tumor cells. Therefore,
      FGF2 has been considered as an important target in cancer therapy. In this study,
      we identified a novel FGF2-binding short peptide (P8, PLLQATAGGGS-NH2) using
      phage display technology and alanine scanning. The P8 peptide suppressed FGF2
      induced proliferation with no cytotoxic effect on cells, arrested the cycle at
      the G0/G1 phase in B16-F10 cells, and downregulated the activation of fibroblast
      growth factor receptor substrate 2alpha (FRS2alpha)/ERK cascade in B16-F10, NIH
      H460, and SGC-7901 cells. Besides, P8 peptide can also inhibit the
      phosphorylation of FRS2alpha stimulated by FGF1 and KGF2. These implied that P8
      peptide may develop as a multi-target antagonist peptide contributing to tumor
      treatment.

PMID- 25062725
TI  - Barriers in access to healthcare services for chronic patients in times of
      austerity: an empirical approach in Greece.
AB  - OBJECTIVES: To investigate the magnitude of barriers in access to health services
      for chronic patients and the socioeconomic and demographic characteristics that
      affect them. METHODS: A cross-sectional study was conducted in 1,594 chronic
      patients suffering from diabetes, hypertension, COPD and Alzheimer. Logistic
      regression analyses were carried out in order to explore the factors related to
      economic and geographical barriers in access, as well as the determinants of
      barriers due to waiting lists. RESULTS: A total of 25% of chronic patients face
      geographical barriers while 63.5% and 58.5% of them are in front of economic and
      waiting list barriers, respectively. Unemployed, low-income and low-educated are
      more likely to face economic barriers in access. Moreover, women, low-income
      patients, and patients with lower health status are more likely to be in front of
      geographical barriers. In addition, the probability of waiting lists occurrence
      is greater for unemployed, employees and low income patients. CONCLUSIONS:
      Barriers in access can be mainly attributed to income decrease and unemployment.
      In this context, health policy measures are essential for removing barriers in
      access. Otherwise, inequalities may increase and chronic patients' health status
      will be deteriorated. These consequences imply adverse effects on health
      expenditure.

PMID- 25062724
TI  - From conventional chemotherapy to targeted therapy: use of monoclonal antibodies
      (moAbs) in gastrointestinal (GI) tumors.
AB  - In recent years, significant progress has been made in the diagnosis and
      treatment of gastrointestinal cancers. Researches and clinicians however are
      still faced with challenges, not the least is the detection and management of
      tumors with varied gene mutation status. Clarification of the molecular pathology
      of gastrointestinal cancers may improve treatment options as well as quality of
      life and the long-term survival of this patient class. Therefore, molecular
      targeted therapies have emerged as clinically useful drugs for gastrointestinal
      cancers cure, and predictive biomarkers have been heralded as the way to develop
      the right drug for the right patient. Moving from such appealing molecular
      background, we wrote an overview of the main targeted therapies, with particular
      interest to monoclonal antibodies that have already been approved in clinical
      practice or are being tested in gastrointestinal cancers treatment. 

PMID- 25062726
TI  - Association between dietary intake of flavonoid and bone mineral density in
      middle aged and elderly Chinese women and men.
AB  - SUMMARY: This large cross-sectional study examined the associations of dietary
      intakes of total flavonoids and their subtypes with bone density in women and
      men. We found that greater flavonoid intake was associated with higher bone
      density in women but not in men. INTRODUCTION: Studies in vitro and in animal
      models suggest a potential effect of flavonoids on bone health. Few studies have
      examined the association between the habitual intake of flavonoids and bone
      mineral density (BMD) in humans. METHODS: The cross-sectional study recruited
      2,239 women and 1,078 men. A semiquantitative food frequency questionnaire was
      administered in face-to-face interviews to assess habitual dietary flavonoid
      intake using food composition databases. BMD was measured over the whole body
      (WB) and in the femoral neck (FN) and lumbar spine (LS) by dual-energy X-ray
      absorptiometry (DXA). RESULTS: After adjusting for covariates, women who consumed
      higher total flavonoids, and the subtypes of flavonols, flavan-3-ols, flavones,
      and proanthocyanidins tended to have greater BMD at the WB, LS, and FN (all P
      trend < 0.05). Women in the highest (vs. the lowest) quartile of total flavonoids
      intake had 0.020 (1.91 %), 0.021 (2.51 %), and 0.013 (1.99 %) g/cm(2) greater BMD
      at the whole body, LS, and FN, respectively. For the subtypes of flavonoids, the
      corresponding differences in BMD (in g/cm(2)) were 0.012-0.021 (flavan-3-ols),
      0.013-0.020 (flavonols), 0.016-0.019 (flavones), and 0.014-0.016
      (proanthocyanidins), respectively. A higher intake of flavonones was associated
      with a greater BMD at the whole body (P-trend 0.041) and the FN (P-trend 0.022).
      In men, there were no significant positive associations between the consumption
      of total flavonoids and the subclasses and BMD at any sites. CONCLUSION: Dietary
      flavonoids intake was positively associated with BMD in women. Further large
      studies are needed to clarify this issue in men.

PMID- 25062727
TI  - Low serum concentrations of alpha-tocopherol are associated with increased risk
      of hip fracture. A NOREPOS study.
AB  - We investigated the risk of hip fracture according to circulating alpha
      tocopherol, a plant-derived substance with antioxidant properties, in community
      dwelling older Norwegians. We found a linear increasing risk of hip fracture with
      lower serum alpha-tocopherol concentrations, with a 51% higher risk in the lowest
      compared to the highest quartile. INTRODUCTION: Oxidative stress is a suggested
      contributing cause of osteoporosis and fractures. Vitamin E (alpha-tocopherol)
      has potent antioxidant properties in humans. The relationship between circulating
      alpha-tocopherol and fracture risk is not established. The aim of this study was
      to investigate the association between serum alpha-tocopherol concentrations and
      risk of hip fracture during up to 11 years of follow-up. METHODS: We performed a
      case-cohort analysis among 21,774 men and women aged 65-79 years who participated
      in four community-based health studies in Norway 1994-2001. Serum alpha
      tocopherol concentrations at baseline were determined in 1,168 men and women who
      subsequently suffered hip fractures (median follow-up 8.2 years) and in a random
      sample (n = 1,434) from the same cohort. Cox proportional hazard regression
      adapted for gender-stratified case-cohort data was performed. RESULTS: Median
      (25, 75 percentile) serum alpha-tocopherol was 30.0 (22.6, 38.3) MUmol/L, and it
      showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11
      (95% confidence interval (CI) 1.04-1.20) per 10-MUmol/L decrease in serum alpha
      tocopherol, adjusted for gender and study center. The lowest compared to the
      highest quartile conferred an HR of 1.51 (95% CI 1.17-1.95), adjusted for gender
      and study center. Adjustment for smoking, month of blood sample, BMI, education,
      physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D)
      yielded similar results. Taking serum total cholesterol concentration into
      account attenuated the association somewhat: HR of hip fracture was 1.37 (95% CI
      1.05-1.77) in first versus fourth quartile of serum alpha-tocopherol/total
      cholesterol ratio. CONCLUSIONS: Low serum concentrations of alpha-tocopherol were
      associated with increased risk of hip fracture in older Norwegians.

PMID- 25062728
TI  - Huntingtin: here, there, everywhere!
AB  - Huntingtin is the protein mutated in Huntington disease, a dominant inherited
      neurodegenerative disorder. Huntingtin is ubiquitously expressed throughout the
      body, however its role outside the central nervous system has been overlooked.
      This review focuses on the peripheral distribution of huntingtin. It also
      highlights that huntingtin has central cellular functions, the importance of
      which may extend beyond the nervous system. Because of the breadth of huntingtin
      expression and functions, mutant huntingtin undoubtedly causes peripheral
      disturbances and may be involved in other non neuronal pathologies. 

PMID- 25062729
TI  - Surveying the landscape of Huntington's disease mechanisms, measurements, and
      medicines.
AB  - Though 20 years have now passed since the cloning of the huntingtin gene (HTT),
      there remains no treatment for Huntington's Disease (HD) that alters the course
      of disease or lifespan of patients. The reasons for this are manifold, and likely
      have to do with the diverse cellular pathways disrupted by mutant HTT (mHTT)
      protein expression. Furthermore, the evaluation of efficacy using a putative
      intervention is complex, largely due to the slow course of disease and
      variability in the classic techniques for evaluating patient symptoms and quality
      of life, which make the patient populations and duration of trials particularly
      imposing. However, there are signs for hope both in the clinic and at the bench.
      This review serves three purposes. It discusses the known cellular pathologies in
      HD, the current and upcoming methods for clinical evaluation of disease progress,
      and the tested and untested interventions proposed to counter the progression in
      animal models and patients. With the vast knowledge of pathology accumulated over
      two decades of modeling HD in animals and following it in patients, as well as
      the advances in intervention techniques both pharmaceutical and genetic, there is
      reason for optimism in the field. Such optimism can only be tempered by the lack
      of success in the clinic to this point, though patients, scientists, and
      clinicians all remain enthusiastic about each new trial, and progress can only
      continue until an effective treatment is found. 

PMID- 25062730
TI  - In vivo identification of therapeutic constructs from pooled candidates in HD
      model mice.
AB  - Rapidly identifying targets for Huntington's Disease (HD) therapeutics in
      relevant mouse models could hasten the development of patient interventions. We
      have recently described a method for rapidly and quantitatively measuring the
      progression of HD-like symptoms in mouse models. Because this method uses flow
      cytometry to measure GFP levels in affected neurons, it is amenable to pooled
      approaches. Here we describe a continuation of this work, using pools of shRNA
      delivering AAV vectors and high throughput sequencing to determine which hairpins
      in a mixed population are most effective at preventing the transcriptional
      dysregulation phenotype of R6/2 mice. 

PMID- 25062731
TI  - An independent study of the preclinical efficacy of C2-8 in the R6/2 transgenic
      mouse model of Huntington's disease.
AB  - BACKGROUND: C2-8 is a small molecule inhibitor of polyglutamine aggregation and
      can reduce photoreceptor neurodegeneration in a Drosophila model of Huntington's
      disease (HD). Further preclinical studies have shown that oral administration of
      C2-8 in R6/2 HD transgenic mice can penetrate into the brain, reduce mHTT-exon1
      aggregation, improve motor performance and diminish striatal neuron atrophy.
      OBJECTIVE: In this independent preclinical study, we aimed to evaluate the
      pharmacokinetic properties and therapeutic efficacy of C2-8 intraperitoneal (IP)
      delivery in the R6/2 HD mouse. METHODS: R6/2 mice were IP injected with low dose
      C2-8 (10 mg/kg), high dose C2-8 (20 mg/kg), or vehicle twice daily from 3 weeks
      to 3 months old. Longitudinal behavioral tests (accelerating Rotarod and wire
      hang) were performed to evaluate the motor deficits, and neuropathology was
      measured by unbiased stereology. RESULTS: We confirmed that the compound has good
      blood-brain-barrier penetration after acute or sub-chronic intraperitoneal
      delivery. Chronic treatment with C2-8 in R6/2 mice results in a significant
      reduction of nuclear mHTT aggregate volume in the brains, replicating a key
      finding of C2-8 as a polyglutamine aggregation inhibitor in vivo. However, by
      comparing HD mice with C2-8 treatment to those with vehicle treatment, we were
      unable to demonstrate significant amelioration of motor deficits using Rotarod
      and wire-hang tests. Moreover, we did not observe improvement in the striatal
      neurodegenerative pathology, as measured by brain weight, striatal volume, and
      striatal neuron volume in the C2-8 treated R6/2 mice. CONCLUSIONS: Our study
      supports the practice of independent preclinical studies for novel molecules in
      HD therapeutic development and suggests that the use of alternative delivery
      strategies and full-length HD mouse models are likely needed to further assess
      whether the aggregate-inhibiting properties of C2-8 can be consistently
      translated into a preclinical benefit in HD mice.

PMID- 25062733
TI  - Increased Steady-State Mutant Huntingtin mRNA in Huntington's Disease Brain.
AB  - BACKGROUND: Huntington's disease is caused by expansion of CAG trinucleotide
      repeats in the first exon of the huntingtin gene, which is essential for both
      development and neurogenesis. Huntington's disease is autosomal dominant. The
      normal allele contains 6 to 35 CAG triplets (average, 18) and the mutant, disease
      causing allele contains >36 CAG triplets (average, 42). OBJECTIVE: We examined
      279 postmortem brain samples, including 148 HD and 131 non-HD controls. A total
      of 108 samples from 87 HD patients that are heterozygous at SNP rs362307, with a
      normal allele (18 to 27 CAG repeats) and a mutant allele (39 to 73 CAG repeats)
      were used to measure relative abundance of mutant and wild-type huntingtin mRNA.
      METHODS: We used allele-specific, quantitative RT-PCR based on SNP heterozygosity
      to estimate the relative amount of mutant versus normal huntingtin mRNA in
      postmortem brain samples from patients with Huntington's disease. RESULTS: In the
      cortex and striatum, the amount of mRNA from the mutant allele exceeds that from
      the normal allele in 75% of patients. In the cerebellum, no significant
      difference between the two alleles was evident. Brain tissues from non-HD
      controls show no significant difference between two alleles of huntingtin mRNAs.
      Allelic differences were more pronounced at early neuropathological grades
      (grades 1 and 2) than at late grades (grades 3 and 4). CONCLUSION: More mutant
      HTT than normal could arise from increased transcription of mutant HTT allele, or
      decreased clearance of mutant HTT mRNA, or both. An implication is that equimolar
      silencing of both alleles would increase the mutant HTT to normal HTT ratio.

PMID- 25062734
TI  - Insulin sensitivity and early-phase insulin secretion in normoglycemic
      Huntington's disease patients.
AB  - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative
      disorder caused by an expanded CAG repeat in exon 1 of the HTT gene. There is
      increasing evidence pointing towards an involvement of the endocrine system in
      HD. Recent studies, investigating the increased risk of diabetes mellitus and
      impaired insulin sensitivity and secretion in HD patients, led to contradictory
      results. OBJECTIVE: To investigate glucose homeostasis in HD. METHODS: Twenty
      eight consecutive patients with HD and 28 healthy controls were matched for age,
      sex, and BMI. Diagnosis of HD was confirmed genetically. Clinical tools for
      assessment were the Unified Huntington's Disease Rating Scale (UHDRS) motor
      section and the Total Function Capacity (TFC). Basal metabolic and endocrine
      investigations and a 2-hour 75-g oGTT were performed. We used the homeostasis
      model assessment of insulin resistance (HOMA-IR) as index of insulin sensitivity
      and the insulinogenic index to assess insulin secretion. RESULTS: HD patients did
      not differ from the controls with respect to fasting plasma glucose, insulin
      sensitivity and secretion. CAG expansion size, disease stage and duration, or BMI
      did not influence HOMA-IR and insulinogenic index. Patients showed lower serum
      glucose (-19%) and insulin levels (-48%) at 30 min and higher serum insulin
      levels at 90 (+132%) and 120 min (+380%). CONCLUSIONS: Our data do not support an
      increased risk of diabetes among HD patients although they show glucose
      regulation abnormalities with a flat glucose curve and delayed insulin peak after
      oral glucose load.

PMID- 25062735
TI  - Depressed mood and suicidality in individuals exposed to tetrabenazine in a large
      Huntington disease observational study.
AB  - BACKGROUND: Tetrabenazine, a treatment for chorea in Huntington disease, carries
      a boxed warning due to safety, especially related to suicidality. OBJECTIVE: To
      compare the frequency of depressed mood and suicidality among a closely monitored
      cohort of individuals with Huntington disease who were exposed and not exposed to
      tetrabenazine. METHODS: A longitudinal prospective study involving 1360
      individuals with HD evaluated at 48 research centers in Australia, Canada, and
      the United States was examined for frequency of depressed mood that triggered a
      risk assessment, suicidal thoughts, suicide attempts, and completed suicide among
      individuals with prior, new, and no exposure to tetrabenazine.. Seventy-seven
      individuals were on tetrabenazine at study enrollment (prior exposure), 64
      individuals were exposed to tetrabenazine during the study's course (new
      exposure), and 1219 individuals had no exposure to tetrabenazine. RESULTS: The
      hazard ratio for depressed mood among those with prior exposure to tetrabenazine
      compared to no exposure was 0.9 (95% CI, 0.5-1.6) and for those with new exposure
      compared to no exposure was 1.2 (95% CI, 0.8-1.9). One individual (1.3%) with
      prior exposure, one individual (1.6%) with new exposure, and 35 individuals
      (2.9%) with no exposure to tetrabenazine reported suicidal thoughts. The hazard
      ratio for suicidal ideation among those with prior exposure to tetrabenazine
      compared to no exposure was 0.5 (95% CI, 0.1-3.8) and for those with new exposure
      to tetrabenazine compared to no exposure was 0.6 (95% CI, 0.1-4.4). Among
      individuals with prior or new exposure to tetrabenazine, no suicide attempts or
      suicides occurred. Among those with no exposure to tetrabenazine 17 suicide
      attempts (1.4%) and four suicides (0.3%) occurred. CONCLUSIONS: In a large
      observational study with close clinical supervision, tetrabenazine treatment was
      not associated with an increased risk of depressed mood, suicidal ideation,
      suicide attempts, or suicide.

PMID- 25062732
TI  - Regional atrophy associated with cognitive and motor function in prodromal
      Huntington disease.
AB  - BACKGROUND: Neuroimaging studies suggest that volumetric MRI measures of specific
      brain structures may serve as excellent biomarkers in future clinical trials of
      Huntington disease (HD). OBJECTIVE: Demonstration of the clinical significance of
      these measures is an important step in determining their appropriateness as
      potential outcome measures. METHODS: Measures of gray- and white-matter lobular
      volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus,
      nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals
      who tested positive for the HD gene expansion, but were not yet exhibiting signs
      or symptoms severe enough to warrant diagnosis ("pre-HD"). MRI volumes (corrected
      for intracranial volume) were correlated with cognitive, motor, psychiatric, and
      functional measures known to be sensitive to subtle changes in pre-HD. RESULTS:
      Caudate, putamen, and globus pallidus volumes consistently correlated with
      cognitive and motor, but not psychiatric or functional measures in pre-HD.
      Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray
      matter, also correlated with some of the motor and cognitive measures.
      CONCLUSIONS: Results of regression analyses suggest that volumes of basal ganglia
      structures contributed more highly to the prediction of most motor and cognitive
      variables than volumes of other brain regions. These results support the use of
      volumetric measures, especially of the basal ganglia, as outcome measures in
      future clinical trials in pre-HD. Results may also assist investigators in
      selecting the most appropriate measures for treatment trials that target specific
      clinical features or regions of neuropathology.

PMID- 25062736
TI  - Corpus callosal atrophy in premanifest and early Huntington's disease.
AB  - BACKGROUND: Volumetric MRI studies have highlighted the pronounced loss of white
      matter in premanifest and early Huntington's Disease (HD). The current study
      focussed on the corpus callosum (CC) since it provides interhemispheric
      connections to vulnerable cortical areas. OBJECTIVES: To investigate cross
      sectional and longitudinal group differences in CC volume and hypothesis-driven
      associations with three cognitive tasks. METHODS: Baseline and 24-month 3T MRI
      were analysed from 106 premanifest (PreHD), (59 preHD-A >=10.8 and 47 preHD-B
      <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2
      (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated
      technique for CC delineation. Between-group differences in volume and 24-month
      atrophy rates, and correlations with cognitive performance were investigated
      using regression models, adjusting for potential confounders. RESULTS: PreHD-B,
      HD1 and HD2 had statistically significantly smaller baseline CC volumes (p <
      0.001) and all groups had elevated 24-month atrophy rates compared with controls
      (p < 0.001). Smaller baseline CC volume was associated with impaired performance
      in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non
      statistically significant relationships with Stroop Word Reading were shown in
      both gene-positive groups. There was no evidence of an association with the Trail
      Making B task. CONCLUSIONS: We found reduced CC volume and elevated 24-month
      atrophy rates, even in individuals far from disease onset. Structural
      degeneration of interhemispheric connections may contribute to cognitive
      deficits, such as performance in the Circle Tracing Indirect task in HD.
      Examination of different image acquisitions may provide more specific information
      about underlying CC degeneration.

PMID- 25062737
TI  - Interplay between steroid signalling and microRNAs: implications for hormone
      dependent cancers.
AB  - Hormones are key drivers of cancer development. To date, interest has largely
      been focussed on the classical model of hormonal gene regulation, but there is
      increasing evidence for a role of hormone signalling pathways in post
      translational regulation of gene expression. In particular, a complex and dynamic
      network of bi-directional interactions with microRNAs (miRs) at all stages of
      biogenesis and during target gene repression is emerging. miRs, which act mainly
      by negatively regulating gene expression through association with 3'-UTRs of mRNA
      species, are increasingly understood to be important in development, normal
      physiology and pathogenesis. Given recent demonstrations of altered miR profiles
      in a diverse range of cancers, their ability to function as oncogenes or tumour
      suppressors, and hormonal regulation of miRs, understanding mechanisms by which
      miRs are generated and regulated is vitally important. miRs are transcribed by
      RNA polymerase II and then processed in the nucleus by the Drosha-containing
      Microprocessor complex and in the cytoplasm by Dicer, before mature miRs are
      incorporated into the RNA-induced silencing complex. It is increasingly evident
      that multiple cellular signalling pathways converge upon the miR biogenesis
      cascade, adding further layers of regulatory complexity to modulate miR
      maturation. This review summarises recent advances in identification of novel
      components and regulators of the Microprocessor and Dicer complexes, with
      particular emphasis on the role of hormone signalling pathways in regulating
      their activity. Understanding hormone regulation of miR production and how this
      is perturbed in cancer are critical for the development of miR-based therapeutics
      and biomarkers.

PMID- 25062739
TI  - Noncoding RNAs and the control of hormonal signaling via nuclear receptor
      regulation.
AB  - Despite its identification over 100 years ago, new discoveries continue to add to
      the complexity of the regulation of the endocrine system. Today the nuclear
      receptors (NRs) that play such a pivotal role in the extensive communication
      networks of hormones and gene expression remain an area of intense research. By
      orchestrating core processes, from metabolism to organismal development, the gene
      expression programs they control are dependent on their cellular context, their
      own levels, and those of numerous co-regulatory proteins. A previously unknown
      component of these networks, noncoding RNAs (ncRNAs) are now recognized as potent
      regulators of NR signaling, influencing receptor and co-factor levels and
      functions while being reciprocally regulated by the NRs themselves. This review
      explores the regulation enacted by microRNAs and long ncRNAs on NR function,
      using representative examples to show the varied roles of ncRNAs, in turn
      producing significant effects on the NR functional network in health and disease.

PMID- 25062738
TI  - TRPA1 and TRPV4 activation in human odontoblasts stimulates ATP release.
AB  - The mechanism of pain in dentine hypersensitivity is poorly understood but
      proposed to result from the activation of dental sensory neurons in response to
      dentinal fluid movements. Odontoblasts have been suggested to contribute to
      thermal and mechanosensation in the tooth via expression of transient receptor
      potential (TRP) channels. However, a mechanism by which odontoblasts could
      modulate neuronal activity has not been demonstrated. In this study, we
      investigated functional TRP channel expression in human odontoblast-like cells
      and measured ATP release in response to TRP channel activation. Human
      immortalized dental pulp cells were driven toward an odontoblast phenotype by
      culture in conditioned media. Functional expression of TRP channels was
      determined with reverse transcription polymerase chain reaction and ratiometric
      calcium imaging with Fura-2. ATP release was measured using a luciferin
      luciferase assay. Expression of mRNA for TRPA1, TRPV1, and TRPV4 but not TRPM8
      was detected in odontoblasts by reverse transcription polymerase chain reaction.
      Expression of TRPV4 protein was detected by Western blotting and
      immunocytochemistry. The TRPA1 agonists allyl isothiocyanate and cinnamaldehyde
      and the TRPV4 agonist GSK1016790A caused a concentration-dependent increase in
      intracellular Ca(2+) concentration that was inhibited by the selective
      antagonists HC030031, AP18, and HC067047, respectively. In contrast, exposure to
      the TRPV1 agonist capsaicin or the TRPM8 agonist icilin had no effect on
      intracellular Ca(2+) concentration. Treatment with allyl isothiocyanate,
      cinnamaldehyde, or GSK1016790A caused an increase in ATP concentration in culture
      medium that was abolished by preincubation with TRP channel antagonists. These
      data demonstrate that activation of TRPA1 and TRPV4 channels in human odontoblast
      like cells can stimulate ATP release. We were unable to confirm the presence of
      thermosensitive TRPV1 and TRPM8 that has previously been reported in
      odontoblasts. 

PMID- 25062740
TI  - Comparison of the laryngoscopy views with the size 1 Miller and Macintosh
      laryngoscope blades lifting the epiglottis or the base of the tongue in infants
      and children <2 yr of age.
AB  - BACKGROUND: Miller laryngoscope blades are preferred for laryngoscopy in infants
      and children <2 yr of age. Despite their long history, the laryngeal view with
      the Miller blade size 1 has never been compared with that with the Macintosh
      (MAC) blade in children. This prospective, single-blinded, randomized study was
      designed to compare the laryngeal views with the size 1 Miller and MAC blades in
      children <2 yr. METHODS: With IRB approval, 50 ASA I and II children <2 yr
      undergoing elective surgery were enrolled. After an inhalation induction and
      neuromuscular block with i.v. rocuronium 0.5 mg kg(-1), two laryngeal views were
      obtained with a single blade (Miller or MAC) in each child: one lifting the
      epiglottis and another lifting the tongue base. The best laryngeal views in each
      blade position were photographed with a SONY((r)) Cyber-shot camera and rated by
      a blinded anaesthesiologist using the percentage of glottic opening scale.
      RESULTS: The scores with the Miller blade lifting the epiglottis and the MAC
      blade lifting the tongue base were similar. The scores with the Miller blade
      lifting the epiglottis and the tongue base were similar. The scores for the MAC
      blade lifting the tongue base were greater than those lifting the epiglottis (95%
      confidence interval: 7.6-26.8) (P=0.0004). CONCLUSIONS: In infants and children
      <2 yr of age, optimal laryngeal views may be obtained with either the Miller size
      1 blade lifting the epiglottis or with the Miller or MAC blades lifting the
      tongue base. CLINICAL TRIAL REGISTRATION: NCT01717872 at Clinical Trials.gov.

PMID- 25062741
TI  - Profiling the third-body wear damage produced in CoCr surfaces by bone cement,
      CoCr, and Ti6Al4V debris: a 10-cycle metal-on-metal simulator test.
AB  - Particles of bone cement (polymethyl methacrylate), CoCr and Ti6Al4V were
      compared for their abrasion potential against CoCr substrates. This appears to be
      the first study utilizing CoCr and Ti6Al4V particulates to abrade CoCr bearings
      and the first study profiling the morphology of third-body abrasive wear
      scratches in a hip simulator. The 5 mg debris allotments (median size range 140
      300 um) were added to cups mounted both inverted and anatomically with metal-on
      metal (MOM) bearings in a 10-cycle, hip simulator test. Surface abrasion was
      characterized by roughness indices and scratch profiles. Compared to third-body
      abrasion with metal debris, polymethyl methacrylate debris had minimal effect on
      the CoCr surfaces. In all, 10 cycles of abrasion with metal debris demonstrated
      that roughness indices (Ra, PV) increased approximately 20-fold from the unworn
      condition. The scratch profiles ranged 20-108 um wide and 0.5-2.8 um deep. The
      scratch aspect ratio (W/PV) averaged 0.03, and this very low ratio indicated that
      the 140 um CoCr beads had plastically deformed to create wide but shallow
      scratches. There was no evidence of transfer of CoCr beads to CoCr bearings. The
      Ti64 particles produced similar scratch morphology with the same aspect ratio as
      the CoCr particulates. However, the titanium particulates also showed a unique
      ability to flatten and adhere to the CoCr, forming smears and islands of
      contaminating metal on the CoCr bearings. The morphology of scratches and metal
      transfer produced by these large metal particulates in the simulator appeared
      identical to those reported on retrieved metal-on-metal bearings. 

PMID- 25062742
TI  - Neurological letter from Latvia.

PMID- 25062743
TI  - Mixed messages on progress against HIV.

PMID- 25062745
TI  - Ethnic differences in suicide behavior in Singapore.
AB  - This study examined the ethnic differences in stressors, risk, and protective
      factors among people who attempted suicide in Singapore. A retrospective chart
      review of 626 attempted suicide cases at a hospital in Singapore between 2004 and
      2006 collected information on diagnosis according to DSM-IV-TR criteria. Chi
      square tests was used to compare the sociodemographic characteristics, stressors,
      risk factors, and protective factors among Chinese, Malay, Indian, and other
      ethnic groups. Logistic regression was used to determine the odds ratios of
      having two or more stressors, risk factors, or protective factors for the four
      ethnic groups. Women were more likely than men to attempt suicide, although they
      also were more likely to have two or more suicide protective factors than men. In
      general, older people were more likely to have two or more suicide risk factors
      than the younger groups. Ethnic differences were found in history of psychiatric
      illnesses and unemployment among the risk factors, and for most of the protective
      factors, but none of the stressors. Indians were more likely to have two or more
      protective factors than were Chinese (OR of 7.74, 95% CI [1.04, 8.72]. Future
      suicide prevention programs should target young adults and strengthen the
      protective factors among different ethnic groups. 

PMID- 25062744
TI  - Association of high-density lipoprotein subclasses and incident coronary heart
      disease: The Jackson Heart and Framingham Offspring Cohort Studies.
AB  - AIMS: We aimed to clarify the associations of high-density lipoprotein
      cholesterol (HDL-C) subclasses with incident coronary heart disease (CHD) in two
      large primary prevention cohorts. METHODS: We measured cholesterol at baseline
      from the two major HDL subfractions (larger, more buoyant HDL2 and smaller,
      denser HDL3) separated by density gradient ultracentrifugation in 4114 (mean age
      53.8 years; 64% female) African American participants from the Jackson Heart
      Study and 818 (mean age 57.3 years, 52% female) predominantly Caucasian
      participants from the Framingham Offspring Cohort Study. Multivariable adjusted
      hazard ratios (HRs) for HDL-C and its subclasses were derived from Cox
      proportional hazards regression models to estimate associations with incident CHD
      events including myocardial infarction, CHD death, and revascularization.
      Analyses were performed for each cohort separately and as a combined population.
      RESULTS: In models adjusted for cardiovascular risk factors for the combined
      population, HDL3-C (HR 0.76 per SD increase; 95% confidence interval (CI), 0.62
      0.94; p = 0.01), rather than HDL2-C (HR 0.88 per SD; 95% CI, 0.72-1.09; p = 0.24)
      drove the inverse association of HDL-C (HR 0.79 per SD; 95% CI, 0.64-0.98; p =
      0.03) with CHD. Similar associations were seen in multivariable analyses within
      each cohort including after adjusting for apolipoprotein A1 in the Jackson Heart
      Study. CONCLUSION: Smaller, denser HDL3-C levels are primarily responsible for
      the inverse association between HDL-C and incident CHD in this diverse group of
      primary prevention subjects. These findings have important implications ranging
      from considerations of HDL biology to interpretations of clinical trials
      utilizing HDL-C therapeutics.

PMID- 25062746
TI  - The free and cued selective reminding test distinguishes frontotemporal dementia
      from Alzheimer's disease.
AB  - Memory impairment is often present in frontotemporal dementia (FTD) as a result
      of an inefficient use of learning strategies, sometimes leading to a misdiagnosis
      of Alzheimer's disease (AD). The Free and Cued Selective Reminding Test (FCSRT)
      is a memory test that controls attention and acquisition, by providing category
      cues in the learning process. The main goal of this study was to show the
      usefulness of the FCSRT in the distinction between behavioral (bv-) FTD and AD.
      Three matched subgroups of participants were considered: bv-FTD (n = 32), AD (n =
      32), and a control group of healthy adults (n = 32). Results proved that while AD
      patients exhibited an overall impairment in FCSRT, bv-FTD subjects showed to
      benefit more from the controlled learning through category cues. AD patients were
      25 times more likely to have an impaired FCSRT. The FCSRT has shown its utility
      in the distinction between bv-FTD and AD, therefore increasing the diagnostic
      accuracy. 

PMID- 25062747
TI  - Study protocol for a randomised controlled trial of internet-based cognitive
      behavioural therapy for obsessive-compulsive disorder.
AB  - BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a common chronic psychiatric
      disorder that constitutes a leading cause of disability. Although Cognitive
      Behaviour Therapy (CBT) has been shown to be an effective treatment for OCD, this
      specialised treatment is unavailable to many due to access issues and the social
      stigma associated with seeing a mental health specialist. Internet-based
      psychological treatments have shown to provide effective, accessible and
      affordable treatment for a range of anxiety disorders, and two Randomised
      Controlled Trials (RCTs) have demonstrated the efficacy and acceptability of
      internet-based CBT (iCBT) for OCD, as compared to waitlist or supportive therapy.
      Although these initial findings are promising, they do not isolate the specific
      effect of iCBT. This paper details the study protocol for the first randomised
      control trial evaluating the efficacy of therapist-assisted iCBT for OCD, as
      compared to a matched control intervention; internet-based therapist-assisted
      progressive relaxation training (iPRT). It will aim to examine whether therapist
      assisted iCBT is an acceptable and efficacious treatment, and to examine how
      effectiveness is influenced by patient characteristics. METHOD/DESIGN: A
      randomised controlled trial using repeated measures with two arms (intervention
      and matched control) will be used to evaluate the efficacy and acceptability of
      iCBT for OCD. The RCT will randomise 212 Australian adults with a primary
      diagnosis of OCD into either the active intervention or control condition, for 12
      weeks duration. Outcomes for participants in both study arms will be assessed at
      baseline and post-intervention. Participants in iCBT will be further assessed at
      six month follow-up, while participants in the control condition will be crossed
      over to receive the iCBT intervention and reassessed at post-intervention and six
      month follow-up. The primary outcome will be clinically significant change in
      obsessive-compulsive symptom scores. DISCUSSION: This will be the first known
      therapist assisted internet-based trial of a comprehensive CBT treatment for OCD
      as compared to a matched control intervention. Demonstrating the efficacy of an
      internet-based treatment for OCD will allow the development of models of care for
      broad-based access to an evidence-based but complex treatment.

PMID- 25062748
TI  - Side branch healing patterns of the Tryton dedicated bifurcation stent: a 1-year
      optical coherence tomography follow-up study.
AB  - The bare-metal Tryton Side Branch (SB) StentTM (Tryton Medical, Durham, NC, USA)
      is used with a drug-eluting stent (DES) in the main branch (MB) to treat
      bifurcation lesions. It is argued that a drug-eluting Tryton-version is needed to
      improve clinical outcomes, although previous registries have shown good clinical
      results. More insights in neo-intimal hyperplasia (NIH) growth patterns of the
      Tryton treatment strategy are needed to decide if and where to drug-coat the
      stent. Ten patients returned for follow-up angiography (mean follow-up time 393
      +/- 103 days) and optical coherence tomography (OCT) pullbacks from the MB were
      obtained in all patients and from the SB in six patients. A per-strut analysis
      showed an uncovered strut rate of 0.7 % and an incompletely-apposed strut rate of
      0.8 %. Most incompletely-apposed struts were found at the bifurcation region, in
      the luminal half facing towards the SB. Mean NIH thickness in the proximal MB,
      distal MB and SB were 0.14 +/- 0.11, 0.19 +/- 0.11, and 0.34 +/- 0.19 mm,
      respectively, with a variety of growth patterns observed in the SB. We found good
      vascular healing of the DES in the MB, while healing was less favourably in the
      SB part. Furthermore, we observed a variety of NIH growth patterns in this SB
      part and more studies are needed to investigate the relation between growth
      patterns and clinical outcomes. 

PMID- 25062749
TI  - Synthetic organotelluride compounds induce the reversal of Pdr5p mediated
      fluconazole resistance in Saccharomyces cerevisiae.
AB  - BACKGROUND: Resistance to fluconazole, a commonly used azole antifungal, is a
      challenge for the treatment of fungal infections. Resistance can be mediated by
      overexpression of ABC transporters, which promote drug efflux that requires ATP
      hydrolysis. The Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known
      model used to study this mechanism of antifungal resistance. The present study
      investigated the effects of 13 synthetic compounds on Pdr5p. RESULTS: Among the
      tested compounds, four contained a tellurium-butane group and shared structural
      similarities that were absent in the other tested compounds: a lateral
      hydrocarbon chain and an amide group. These four compounds were capable of
      inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values
      less than 2 MUM and had an uncompetitive pattern of Pdr5p ATPase activity
      inhibition. These organotellurides did not demonstrate cytotoxicity against human
      erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and
      a null mutant strain) even in concentrations above 100 MUM. When tested at 100
      MUM, they could reverse the fluconazole resistance expressed by both the S.
      cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida
      albicans. CONCLUSIONS: We have identified four organotellurides that are
      promising candidates for the reversal of drug resistance mediated by drug efflux
      pumps. These molecules will act as scaffolds for the development of more
      efficient and effective efflux pump inhibitors that can be used in combination
      therapy with available antifungals.

PMID- 25062750
TI  - Characteristics of successful technological interventions in mental resilience
      training.
AB  - In the last two decades, several effective virtual reality-based interventions
      for anxiety disorders have been developed. Virtual reality interventions can also
      be used to build resilience to psychopathology for populations at risk of
      exposure to traumatic experiences and developing mental disorders as a result,
      such as for people working in vulnerable professions. Despite the interest among
      mental health professionals and researchers in applying new technology-supported
      interventions for pre-trauma mental resilience training, there is a lack of
      recommendations about what constitutes potentially effective technology-supported
      resilience training. This article analyses the role of technology in the field of
      stress-resilience training. It presents lessons learned from technology
      developers currently working in the area, and it identifies some key clinical
      requirements for the supported resilience interventions. Two processes made up
      this research: 1) developers of technology-assisted resilience programs were
      interviewed regarding human-computer interaction and system development; 2)
      discussions with clinicians were prompted using technology-centered concept
      storyboards to elicit feedback, and to refine, validate and extend the initial
      concepts. A qualitative analysis of the interviews produced a set of development
      guidelines that engineers should follow and a list of intervention requirements
      that the technology should fulfill. These recommendations can help bridge the gap
      between engineers and clinicians when generating novel resilience interventions
      for people in vulnerable professions. 

PMID- 25062751
TI  - Improving myopia via perceptual learning: is training with lateral masking the
      only (or the most) efficacious technique?
AB  - Perceptual learning produces an improvement in visual functions such as an
      increase in visual acuity (VA) and contrast sensitivity in participants with both
      amblyopia and refractive defects. This improvement has been observed in the
      presence of lateral masking, which is known to bring about lateral interactions
      between detectors in early cortical pathways. Improvement has also been revealed
      in the absence of flankers in healthy individuals and those with amblyopia. This
      study seeks to understand whether a perceptual training regime really needs to be
      based on lateral interactions in cases where poor vision is not due to cortical
      dysfunction, such as myopia. Ten participants with mild myopia (max -2D) were
      recruited. A battery of tests measuring visual function was administered prior to
      (pre-test) and following (post-test) the training. The participants carried out
      an 8-week behavioural training using a single Gabor perceptual learning paradigm,
      completing a total of 24 sessions. Results indicate that training using a single
      Gabor protocol results in a VA improvement of 0.16 logMAR. The present study
      supports the idea that, in the absence of cortical deficits, as is the case in
      myopia, some sort of compensatory mechanism can take place at the cortical level
      by means of perceptual learning, resulting in more effective processing of the
      received blurred input. However, regarding training based on lateral masking,
      here we found that improvement of visual functions was smaller and limited to VA.
      This might suggest that training based on lateral masking, which is able to
      modify the strength of facilitatory and inhibitory lateral interactions, could be
      more effective for optimal recovery of blurred vision. 

PMID- 25062752
TI  - Network meta-analysis to evaluate the effectiveness of interventions to prevent
      falls in children under age 5 years.
AB  - BACKGROUND: This study aimed to simultaneously evaluate the effectiveness of a
      range of interventions to increase the possession of safety equipment or
      behaviours to prevent falls in children under 5 years of age in the home.
      METHODS: A recently published systematic review identified studies to be included
      in a network meta-analysis; an extension of pairwise meta-analysis that enables
      comparison of all evaluated interventions simultaneously, including comparisons
      not directly compared in individual studies. RESULTS: 29 primary studies were
      identified, of which 16 were included in at least 1 of 4 network meta-analyses.
      For increasing possession of a fitted stair gate, the most intensive intervention
      (including education, low cost/free home safety equipment, home safety inspection
      and fitting) was the most likely to be the most effective, with an OR versus
      usual care of 7.80 (95% CrI 3.08 to 21.3). For reducing possession or use of a
      baby walker: education only was most likely to be most effective, with an OR
      versus usual care of 0.48 (95% CrI 0.31 to 0.84). Little difference was found
      between interventions for possession of window locks (most intensive intervention
      versus usual care OR=1.56 (95% CrI 0.02 to 89.8)) and for not leaving a child
      alone on a high surface (education vs usual care OR=0.89 (95% CrI 0.10 to 9.67)).
      There was insufficient evidence for network meta-analysis for possession and use
      of bath mats. CONCLUSIONS: These results will inform healthcare providers of the
      most effective components of interventions and can be used in cost-effectiveness
      analyses.

PMID- 25062753
TI  - Acute urinary morbidity after a permanent 125I implantation for localized
      prostate cancer.
AB  - We evaluated the predictive factors of acute urinary morbidity (AUM) after
      prostate brachytherapy. From November 2005 to January 2007, 62 patients with
      localized prostate cancer were treated using brachytherapy. The (125)Iodine
      ((125)I) seed-delivering method was a modified peripheral pattern. The prescribed
      dose was 144 Gy. Urinary morbidity was scored at 3 months after implantation. The
      clinical and treatment parameters were analysed for correlation with AUM. In
      particular, in this study, Du90 (the minimal dose received by 90% of the
      urethra), Dup90 (the minimal dose received by 90% of the proximal half of the
      urethra on the bladder side) and Dud90 (the minimal dose received by 90% of the
      distal half of the urethra on the penile side) were analysed. We found that 43
      patients (69.4%) experienced acute urinary symptoms at 3 months after
      implantation. Of them, 40 patients had Grade 1 AUM, one patient had Grade 2 pain,
      and two patients had Grade 2 urinary frequency. None of the patients had >=Grade
      3. Univariate and multivariate analysis revealed that Du90 and Dup90 were
      significantly correlated with AUM. In this study, Du90 and Dup90 were the most
      significant predictors of AUM after prostate brachytherapy.

PMID- 25062754
TI  - Effects of structured interview guides and rater monitoring in clinical trials.

PMID- 25062755
TI  - A cognitive-behavioral model of Internet gaming disorder: theoretical
      underpinnings and clinical implications.
AB  - Cognitive contributions to the behaviors observed in substance and non-substance
      addictions have been investigated and characterized. Based on models of drug
      addictions and the extant literature on Internet gaming disorder (IGD), we
      propose a cognitive-behavioral model for conceptualizing IGD. The model focuses
      on three domains and their roles in addictive behaviors. The three domains
      include motivational drives related to reward-seeking and stress-reduction,
      behavioral control relating to executive inhibition, and decision-making that
      involves weighing the pros and cons of engaging in motivated behaviors. Based on
      this model, we propose how behavioral therapies might target these domains in the
      treatment of IGD. 

PMID- 25062756
TI  - Effect of nonsurgical periodontal treatment on glycosylated hemoglobin in
      diabetic patients: a systematic review.
AB  - This review was designed to determine whether non-surgical periodontal treatment
      is able to reduce serum glycosylated hemoglobin (HbA1c) levels in patients with
      diabetes mellitus (DM). Several previous reports showed that scaling and root
      planning (SRP) improve periodontal status in patients with DM, but whether it
      also improves metabolic control of the disease is unclear. A systematic review
      was conducted according to the recommendations of the Cochrane Collaboration and
      PRISMA. A literature search was conducted in October 2012 using three libraries
      (Cochrane, Web of Knowledge, and Scopus) and the keywords "periodontal disease"
      and "diabetes mellitus." Only 21 of the articles met the inclusion criteria for
      this review. A total of 1,454 patients were thus included in this study to
      evaluate whether periodontal treatment improved serum HbA1c levels. Both the
      methodological quality and the risk of bias of each study were taken into account
      using the Jadad scale. Only ten of the included studies had an acceptable-good
      score of 3-5. Fourteen of the studies reported a significant decrease in serum
      HbA1c levels (p < 0.05) after periodontal treatment. The remaining seven studies
      failed to find a significant decrease in serum HbA1c. The findings of this review
      suggest that the published literature is insufficient and inconclusive to clearly
      support periodontal treatment as a means to improve serum HbA1c levels in
      patients with type 1 DM. It also demonstrates the need for homogeneous studies,
      with larger samples and longer follow-up periods, to properly address this
      question.

PMID- 25062757
TI  - Theoretical insight into the relationship between the structures of antimicrobial
      peptides and their actions on bacterial membranes.
AB  - Antimicrobial peptides with diverse cationic charges, amphiphathicities, and
      secondary structures possess a variety of antimicrobial activities against
      bacteria, fungi, and other generalized targets. To illustrate the relationship
      between the structures of these peptide and their actions at microscopic level,
      we present systematic coarse-grained dissipative particle dynamics simulations of
      eight types of antimicrobial peptides with different secondary structures
      interacting with a lipid bilayer membrane. We find that the peptides use multiple
      mechanisms to exert their membrane-disruptive activities: A cationic charge is
      essential for the peptides to selectively target negatively charged bacterial
      membranes. This cationic charge is also responsible for promoting
      electroporation. A significant hydrophobic portion is necessary to disrupt the
      membrane through formation of a permeable pore or translocation. Alternatively,
      the secondary structure and the corresponding rigidity of the peptides determine
      the pore structure and the translocation pathway. 

PMID- 25062758
TI  - Antiepileptic medications increase osteoporosis risk in male fabry patients: bone
      mineral density in an Australian cohort.
AB  - BACKGROUND: Fabry disease (FD) is an inherited X-linked lysosomal storage disease
      with widespread clinical manifestations. Small prospective studies have shown
      increased osteopenia and osteoporosis in male FD patients. Limited information
      however exists about bone metabolism and osteoporosis risk factors within this
      group. We reviewed osteoporosis risk factors within our cohort. METHODS: A
      retrospective analysis of bone mineral density (BMD) results and fracture
      incidence in 44 patients (22 males and 22 females) was undertaken. Dual X-ray
      absorptiometry scans were performed at the lumbar spine, hip and femoral neck.
      The impact of risk factors including renal function, antiepileptic drug (AED),
      analgesia and vitamin D levels were assessed. RESULTS: Male FD patients had low T
      scores at all sites (spine -1.2 +/- 1.06, hip -1.6 +/- 0.9, femoral neck -2.23 +/
      1.01). Female T scores showed more typical distribution (spine -0.07 +/- 1.47,
      hip 0.02 +/- 1.14, femoral neck -0.49 +/- 1.31). A higher incidence of osteopenia
      and/or osteoporosis occurred in males versus females (spine 46.9% versus 31.8%,
      hip 75.5% versus 18.2% and femoral neck 86.4% versus 45.5%). Multiple regression
      analysis showed a 50.8% (p < 0.001) reduction in femoral neck BMD with AED usage,
      after adjustment for age, gender and renal function. Non-traumatic fractures
      occurred in 27.3% males over 205 patient-years versus 4.6% in females over 149
      patient-years, p = 0.095. CONCLUSIONS: Low bone density was highly prevalent in
      male patients with increased incidence of non-traumatic fractures. AED usage
      significantly reduces BMD. Treatment to prevent BMD deterioration will depend on
      determining the bone turnover status.

PMID- 25062759
TI  - Linolenic acid provides multi-cellular protective effects after photothrombotic
      cerebral ischemia in rats.
AB  - Alpha-linolenic acid (LIN) has been shown to provide neuroprotective effects
      against cerebral ischemia. LIN is a potent activator of TREK-1 channel and LIN
      induced neuroprotection disappears in Trek1-/- mice, suggesting that this channel
      is directly related to the LIN-induced resistance of brain against ischemia.
      However, the cellular mechanism underlying LIN induced neuroprotective effects
      after ischemia remains unclear. In this study, using a rat photochemical brain
      ischemia model, we investigated the effects of LIN on the protein abundance of
      astrocytic glutamate transporter and AQP4, microglia activation, cell apoptosis
      and behavioral recovery following ischemia. Administration of LIN rescued the
      protein abundance of astrocytic glutamate transporter GLT-1, decreased the
      protein abundance of AQP4 and brain edema, inhibited microglia activation,
      attenuated cell apoptosis and improved behavioral function recovery. Meanwhile,
      TREK-1 was widely distributed in the cortex and hippocampus, primarily localized
      in astrocytes and neurons. LIN could potentiate the TREK-1 mediated astrocytic
      passive conductance and hyperpolarize the membrane potential. Our results suggest
      that LIN provides multiple cellular neuroprotective effects in cerebral ischemia.
      TREK-1 may serve as a promising multi-mechanism therapeutic target for the
      treatment of stroke. 

PMID- 25062760
TI  - Huntington's disease in popular culture: a brief historical perspective.

PMID- 25062761
TI  - Aquatherapy for neurodegenerative disorders.
AB  - Aquatherapy is used for rehabilitation and exercise; water provides a
      challenging, yet safe exercise environment for many special populations. We have
      reviewed the use of aquatherapy programs in four neurodegenerative disorders:
      Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and
      Huntington's disease. Results support the use of aquatherapy in Parkinson's
      disease and multiple sclerosis, however further evidence is required to make
      specific recommendations in all of the aforementioned disorders. 

PMID- 25062762
TI  - Skeletal muscle atrophy in R6/2 mice - altered circulating skeletal muscle
      markers and gene expression profile changes.
AB  - BACKGROUND: In addition to classical neurological symptoms, Huntington's disease
      (HD) is complicated by peripheral pathology, including progressive skeletal
      muscle wasting, and common skeletal muscle gene expression changes have been
      shown in HD mice and human HD. OBJECTIVE: To highlight possible mechanisms
      underlying muscle wasting in HD, we examined gene expression in pathways
      governing skeletal muscle contractility, skeletal myogenesis, skeletal muscle
      wasting, apoptosis and the NFkappaB signaling pathway in two HD mouse models (the
      transgenic R6/2 and full-length knock-in Q175). In addition, we assessed
      circulating markers that increase in response to skeletal muscle injury, skeletal
      Troponin I (sTnI), fatty acid binding protein 3 (FABP3), and Myosin light chain 3
      (Myl3). METHODS: We measured gene expression in muscle tissue as well as in
      cultured primary myocytes using qPCR. Concentrations of cytokines and muscle
      proteins were obtained using multiplex ELISA. RESULTS: Circulating markers of
      muscle injury (sTnI, FABP3, and Myl3) were significantly increased in mouse
      serum. In skeletal muscle, we observed reduced gene expression of components
      involved in muscle contractility, with pronounced downregulation of Acta1, Myh2
      and Tnni2, among others. Alongside, we found increased expression of caspases (3
      and 8) and key elements of the NFkappaB signaling pathway, p65/RelA, Tradd, and
      TRAF5. We also found similar gene expression alterations in cultured primary
      myocytes from R6/2 mice stimulated with TNF-alpha. CONCLUSIONS: Our results
      indicate that activation of apoptotic and NFkappaB pathways occur alongside down
      regulation of key compartments of the muscle contractility unit in skeletal
      muscle of HD mice, and muscle atrophy could possibly be a source of circulating
      disease progression markers.

PMID- 25062763
TI  - Changes in cognitive control in pre-manifest Huntington's disease examined using
      pre-saccadic EEG potentials - a longitudinal study.
AB  - BACKGROUND: It is well-known that Huntington's disease (HD) affects saccadic
      processing. However, saccadic dysfunctions in HD may be seen as a result of
      dysfunctional processes occurring at the oculomotor level prior to the execution
      of saccades, i.e., at a pre-saccadic level. Virtually nothing is known about
      possible changes in pre-saccadic processes in HD. OBJECTIVE: This study examines
      pre-saccadic processing in pre-manifest HD gene mutation carriers (pre-HDs) by
      using clinically available EEG measures. METHODS: Error rates, pre-saccadic EEG
      potentials and saccade onset EEG potentials were measured in 14 pre-HDs and case
      matched controls performing prosaccades and antisaccades in a longitudinal study
      over a 15-month period. RESULTS: The results show that pre-saccadic potentials
      were changed in pre-HDs, relative to controls and also revealed changes across
      the 15-month longitudinal period. In particular, pre-saccadic ERP in pre-HDs were
      characterized by lower amplitudes and longer latencies, which revealed
      longitudinal changes. These changes were observed for anti-saccades, but not for
      pro-saccades. Overt saccadic trajectories (potentials) were not different to
      those in controls, showing that pre-saccadic processes are sensitive to subtle
      changes in fronto-striatal networks in pre-HDs. CONCLUSIONS: Deficits in pre
      saccadic processes prior the execution of an erroneous anti-saccade can be seen
      as an effect of dysfunctional cognitive control in HD. This may underlie saccadic
      abnormalities and hence a major phenotype of HD. Pre-saccadic EEG potentials
      preceding erroneous anti-saccades are sensitive to pre-manifest disease
      progression in HD.

PMID- 25062764
TI  - Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's
      disease.
AB  - Huntington's disease is an autosomal dominant neurodegenerative disease
      characterized by neuronal degeneration in the basal ganglia and cerebral cortex,
      and a variable symptom profile. Although progressive striatal degeneration is
      known to occur and is related to symptom profile, little is known about the
      cellular basis of symptom heterogeneity across the entire cerebral cortex. To
      investigate this, we have undertaken a double blind study using unbiased
      stereological cell counting techniques to determine the pattern of cell loss in
      six representative cortical regions from the frontal, parietal, temporal, and
      occipital lobes in the brains of 14 Huntington's disease cases and 15 controls.
      The results clearly demonstrate a widespread loss of total neurons and pyramidal
      cells across all cortical regions studied, except for the primary visual cortex.
      Importantly, the results show that cell loss is remarkably variable both within
      and between Huntington's disease cases. The results also show that neuronal loss
      in the primary sensory and secondary visual cortices relate to Huntington's
      disease motor symptom profiles, and neuronal loss across the associational
      cortices in the frontal, parietal and temporal lobes is related to both
      Huntington's disease motor and to mood symptom profiles. This finding
      considerably extends a previous study (Thu et al., Brain, 2010; 133:1094-1110)
      which showed that neuronal loss in the primary motor cortex was related
      specifically to the motor symptom profiles while neuronal loss in the anterior
      cingulate cortex was related specifically to mood symptom profiles. The extent of
      cortical cell loss in the current study was generally related to the striatal
      neuropathological grade, but not to CAG repeat length on the HTT gene. Overall
      our findings show that Huntington's disease is characterized by a heterogeneous
      pattern of neuronal cell loss across the entire cerebrum which varies with
      symptom profile. 

PMID- 25062765
TI  - Rhes suppression enhances disease phenotypes in Huntington's disease mice.
AB  - In Huntington's disease (HD) mutant HTT is ubiquitously expressed yet the
      striatum undergoes profound early degeneration. Cell culture studies suggest that
      a striatal-enriched protein, Rhes, may account for this vulnerability. We
      investigated the therapeutic potential of silencing Rhes in vivo using inhibitory
      RNAs (miRhes). While Rhes suppression was tolerated in wildtype mice, it failed
      to improve rotarod function in two distinct HD mouse models. Additionally, miRhes
      treated HD mice had increased anxiety-like behaviors and enhanced striatal
      atrophy as measured by longitudinal MRI when compared to control treated mice.
      These findings raise caution regarding the long-term implementation of inhibiting
      Rhes as a therapy for HD. 

PMID- 25062766
TI  - Experimental mutagenesis of huntingtin to map cleavage sites: different outcomes
      in cell and mouse models.
AB  - BACKGROUND: N-terminal cleavage products of mutant huntingtin (htt) generate
      pathologic neuronal inclusion bodies. The precise length of the htt fragment,
      termed Cp-A/1, that produces HD pathologic inclusions is unknown. OBJECTIVE: We
      sought to elucidate the protein sequence elements within the N-terminus of htt
      that mediate its proteolysis based on a model in which engineered htt fragments
      terminating at residue 171 are cleaved to produce Cp-A/1 fragments. METHODS: We
      expressed htt N171 cDNAs harboring a series of experimental mutations in the
      presumptive cleavage site that generates Cp-A/1 in cells to identify cleavage
      resistant mutants of htt N171. One of these constructs was expressed in mice,
      followed by analysis using immunoblots of brain extracts and immunohistochemistry
      of transgenic mouse brain tissues. RESULTS: Using the HEK293 cell model,
      mutagenesis studies mapped the cleavage site in htt N171 to sequences between
      residues 105-114. Mutation of 8 positively charged residues (H, K, R) located
      between residues 88 and 114 to alanine to neutralize the charge also blocked the
      generation of Cp-A/1 like fragments. Transgenic mice expressing this latter
      construct, termed N171-82Q-N8, developed phenotypes similar to previously
      characterized N171-82Q transgenic mice, including rotarod deficiency,
      intranuclear inclusions, and premature death. Surprisingly, the N171-82Q-N8
      protein was efficiently cleaved in vivo to produce Cp-A/1 fragments that
      accumulated as insoluble inclusions. CONCLUSION: Mutagenesis of htt to identify
      critical amino acids that direct its cleavage predicted a role for charged
      residues in the sequence flanking the presumptive cleavage site. However, the
      role for these residues could not be confirmed in vivo. The basis for the
      discrepancy between predicted outcomes in HEK293 cells and the mouse models
      remain unresolved, but the data provide another validation of the hypothesis that
      Cp-A/1 fragments of mutant htt can induce HD-like phenotypes.

PMID- 25062767
TI  - The Protein Data Bank archive as an open data resource.
AB  - The Protein Data Bank archive was established in 1971, and recently celebrated
      its 40th anniversary (Berman et al. in Structure 20:391, 2012). An analysis of
      interrelationships of the science, technology and community leads to further
      insights into how this resource evolved into one of the oldest and most widely
      used open-access data resources in biology.

PMID- 25062768
TI  - The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary
      artery on congenital diaphragmatic hernia rabbit model.
AB  - PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with pulmonary
      hypertension which is often difficult to manage, and a significant cause of
      morbidity and mortality. In this study, we have used a rabbit model of CDH to
      evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary
      artery. METHODS: CDH was performed in New Zealand rabbit fetuses (n = 10 per
      group) and compared to controls. Measurements of body, total and left lung
      weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with
      phenylephrine (10 MUM), after which cumulative concentration-response curves to
      glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770
      (sGC activator) were obtained as well as the levels of NO (NO3/NO2). RESULTS:
      LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the
      potency (pEC50) for GTN was markedly lower in CDH (8.25 +/- 0.02 versus 9.27 +/-
      0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in
      CDH (11.7 +/- 0.03 versus 10.5 +/- 0.06; p < 0.01). The NO2/NO3 levels were 62 %
      higher in CDH (p < 0.05). CONCLUSION: BAY 60-2770 exhibits a greater potency to
      relax the pulmonary artery in CDH, indicating a potential use for pulmonary
      hypertension in this disease.

PMID- 25062769
TI  - Urethroscopic holmium: YAG laser ablation for acquired posterior urethral
      diverticulum after repair of anorectal malformations.
AB  - Two patients with acquired posterior urethral diverticulum that is a complication
      of laparoscopic assisted anorectoplasty underwent urethroscopic holmium: YAG
      laser ablation. After the ablation therapies, the size of the diverticulum
      markedly decreased in both patients. Holmium: YAG laser is safe and easy to
      handle in the small pediatric urethra. 

PMID- 25062771
TI  - Fifteen-minute consultation: neuromuscular spinal deformity in disabled children.
AB  - Spinal deformity is common and occasionally inevitable in children with
      disabilities. This article concentrates on non-ambulant children with a spinal
      deformity, and aims to help the paediatrician understand the challenges families
      and spinal surgeons face. 

PMID- 25062770
TI  - Treatment of resistant metastatic melanoma using sequential epigenetic therapy
      (decitabine and panobinostat) combined with chemotherapy (temozolomide).
AB  - PURPOSE: To explore the safety and tolerability of combining two epigenetic
      drugs: decitabine (a DNA methyltransferase inhibitor) and panobinostat (a histone
      deacetylase inhibitor), with chemotherapy with temozolomide (an alkylating
      agent). The purpose of such combination is to evaluate the use of epigenetic
      priming to overcome resistance of melanoma to chemotherapy. METHODS: A Phase I
      clinical trial enrolling patients aged 18 years or older, with recurrent or
      unresectable stage III or IV melanoma of any site. This trial was conducted with
      full Institutional Review Board approval and was registered with the National
      Institutes of Health under the clinicaltrials.gov identifier NCT00925132.
      Patients were treated with subcutaneous decitabine 0.1 or 0.2 mg/kg three times
      weekly for 2 weeks (starting on day 1), in combination with oral panobinostat 10,
      20, or 30 mg every 96 h (starting on day 8), and oral temozolomide 150
      mg/m(2)/day on days 9 through 13. In cycle 2, temozolomide was increased to 200
      mg/m(2)/day if neutropenia or thrombocytopenia had not occurred. Each cycle
      lasted 6 weeks, and patients could receive up to six cycles. Patients who did not
      demonstrate disease progression were eligible to enter a maintenance protocol
      with combination of weekly panobinostat and thrice-weekly decitabine until tumor
      progression, unacceptable toxicity, or withdrawal of consent. RESULTS: Twenty
      patients were initially enrolled, with 17 receiving treatment. The median age was
      56 years. Eleven (65%) were male, and 6 (35%) were female. Eleven (64.7%) had
      cutaneous melanoma, 4 (23.5%) had ocular melanoma, and 2 (11.8%) had mucosal
      melanoma. All patients received at least one treatment cycle and were evaluable
      for toxicity. Patients received a median of two 6-week treatment cycles (range 1
      6). None of the patients experienced DLT. MTD was not reached. Adverse events
      attributed to treatment included grade 3 lymphopenia (24%), anemia (12%),
      neutropenia (12%), and fatigue (12%), as well as grade 2 leukopenia (30%),
      neutropenia (23%), nausea (23%), and lymphopenia (18%). The most common reason
      for study discontinuation was disease progression. CONCLUSIONS: This triple agent
      of dual epigenetic therapy in combination with traditional chemotherapy was
      generally well tolerated by the cohort and appeared safe to be continued in a
      Phase II trial. No DLTs were observed, and MTD was not reached.

PMID- 25062772
TI  - Economic crisis and suicidal behaviour: the role of unemployment, sex and age in
      Andalusia, southern Spain.
AB  - INTRODUCTION: Although suicide rates have increased in some European countries in
      relation to the current economic crisis and austerity policies, that trend has
      not been observed in Spain. This study examines the impact of the economic crisis
      on suicide attempts, the previously neglected endpoint of the suicidal process,
      and its relation to unemployment, age and sex. METHODS: The study was carried out
      in Andalusia, the most populated region of Spain, and which has a high level of
      unemployment. Information on suicide attempts attended by emergency services was
      extracted from the Health Emergencies Public Enterprise Information System
      (SIEPES). Suicide attempts occurring between 2003 and 2012 were included, in
      order to cover five years prior to the crisis (2003-2007) and five years after
      its onset (2008-2012). Information was retrieved from 24,380 cases (11,494 men
      and 12,886 women) on sex, age, address, and type of attention provided. Age
      adjusted suicide attempt rates were calculated. Excess numbers of attempts from
      2008 to 2012 were estimated for each sex using historical trends of the five
      previous years, through time regression models using negative binomial regression
      analysis. To assess the association between unemployment and suicide attempts
      rates, linear regression models with fixed effects were performed. RESULTS: A
      sharp increase in suicide attempt rates in Andalusia was detected after the onset
      of the crisis, both in men and in women. Adults aged 35 to 54 years were the most
      affected in both sexes. Suicide attempt rates were associated with unemployment
      rates in men, accounting for almost half of the cases during the five initial
      years of the crisis. Women were also affected during the recession period but
      this association could not be specifically attributed to unemployment.
      CONCLUSIONS: This study enhances our understanding of the potential effects of
      the economic crisis on the rapidly increasing suicide attempt rates in women and
      men, and the association of unemployment with growing suicidal behaviour in men.
      Research on the suicide effects of the economic crisis may need to take into
      account earlier stages of the suicidal process, and that this effect may differ
      by age and sex.

PMID- 25062773
TI  - Arsenic methylation capacity is associated with breast cancer in northern Mexico.
AB  - Exposure to environmental contaminants, dietary factors and lifestyles may
      explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs)
      in the drinking water is a concern in many regions, such as northern Mexico.
      Studies in several countries have associated the proportion of urinary
      monomethylarsenic (%MMA) with increased risks for many As-related diseases,
      including cancer. To investigate the potential relationships between the risk of
      BC and the capacity to methylate iAs, a hospital-based case-control study (1016
      cases/1028 controls) was performed in northern Mexico. Women were directly
      interviewed about their reproductive histories. The profile of As metabolites in
      urine was determined by HPLC-ICP-MS and methylation capacity was assessed by
      metabolite percentages and indexes. Total urinary As, excluding arsenobetaine
      (TAs-AsB), ranged from 0.26 to 303.29MUg/L. Most women (86%) had TAs-AsB levels
      below As biological exposure index (35MUg/L). Women with higher %MMA and/or
      primary methylation index (PMI) had an increased BC risk (%MMA ORQ5vs.Q1=2.63;
      95%CI 1.89,3.66; p for trend <0.001; PMI ORQ5vs.Q1=1.90; 95%CI 1.39,2.59, p for
      trend <0.001). In contrast, women with higher proportion of urinary
      dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC
      risk (%DMA ORQ5vs.Q1=0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI ORQ5vsQ1=0.42,
      95%CI 0.31,0.59, p for trend <0.001). Neither %iAs nor total methylation index
      was associated to BC risk. Inter-individual variations in iAs metabolism may play
      a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA
      and/or a lower capacity to further methylate MMA to DMA were at higher BC risk. 

PMID- 25062774
TI  - Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by
      regulating MAP kinase and NF-kappaB signaling pathways in SKH-1 hairless mice
      skin.
AB  - Skin cancer is one of the most commonly diagnosed cancers in the United States.
      Exposure to ultraviolet-B (UVB) radiation induces inflammation and
      photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of
      the anthocyanin family, is present in various vegetables and fruits especially in
      edible berries, and displays potent antioxidant and anticarcinogenic properties.
      In this study, we have assessed the in vivo effects of C3G on UVB irradiation
      induced chronic inflammatory responses in SKH-1 hairless mice, a well-established
      model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB
      induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate
      that C3G inhibited glutathione depletion, lipid peroxidation and
      myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly
      decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6
      and TNF-alpha, associated with cutaneous inflammation. Likewise, UVB-induced
      inflammatory responses were diminished by C3G as observed by a remarkable
      reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and
      MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2
      and iNOS levels, which are well-known key mediators of inflammation and cancer.
      Treatment with C3G inhibited UVB-induced nuclear translocation of NF-kappaB and
      degradation of IkappaBalpha in mice skin. Immunofluorescence assay revealed that
      topical application of C3G inhibited the expression of 8-hydroxy-2'
      deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB
      exposed mouse skin. Collectively, these data indicates that C3G can provide
      substantial protection against the adverse effects of UVB radiation by modulating
      UVB-induced MAP kinase and NF-kappaB signaling pathways. 

PMID- 25062775
TI  - Circadian and melatonin disruption by exposure to light at night drives intrinsic
      resistance to tamoxifen therapy in breast cancer.
AB  - Resistance to endocrine therapy is a major impediment to successful treatment of
      breast cancer. Preclinical and clinical evidence links resistance to antiestrogen
      drugs in breast cancer cells with the overexpression and/or activation of various
      pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift
      work or disturbed sleep-wake cycles may lead to an increased risk of breast
      cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the
      nocturnal production of melatonin that inhibits breast cancer growth. In this
      study, we used a rat model of estrogen receptor (ERalpha(+)) MCF-7 tumor
      xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN)
      speed the development of breast tumors, increasing their metabolism and growth
      and conferring an intrinsic resistance to tamoxifen therapy. These
      characteristics were not observed in animals in which the circadian melatonin
      rhythm was not disrupted, or in animals subjected to dLEN if they received
      nocturnal melatonin replacement. Strikingly, our results also showed that
      melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated
      kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and
      tumor regression. Together, our findings show how dLEN-mediated disturbances in
      nocturnal melatonin production can render tumors insensitive to tamoxifen.

PMID- 25062776
TI  - Canopy-level stomatal narrowing in adult Fagus sylvatica under O3 stress - means
      of preventing enhanced O3 uptake under high O3 exposure?
AB  - Spatio-temporally consistent O(3) doses are demonstrated in adult Fagus sylvatica
      from the Kranzberg Forest free-air fumigation experiment, covering cross-canopy
      and whole-seasonal scopes through sap flow measurement. Given O(3)-driven closure
      of stomata, we hypothesized enhanced whole-tree level O(3) influx to be prevented
      under enhanced O(3) exposure. Although foliage transpiration rate was lowered
      under twice-ambient O(3) around noon by 30% along with canopy conductance, the
      hypothesis was falsified, as O(3) influx was raised by 25%. Nevertheless, the
      twice-ambient/ambient ratio of O(3) uptake was smaller by about 20% than that of
      O(3) exposure, suggesting stomatal limitation of uptake. The O(3) response was
      traceable from leaves across branches to the canopy, where peak transpiration
      rates resembled those of shade rather than sun branches. Rainy/overcast-day and
      nightly O(3) uptake is quantified and discussed. Whole-seasonal canopy-level
      validation of modelled with sap flow-derived O(3) flux becomes available in
      assessing O(3) risk for forest trees.

PMID- 25062777
TI  - Functional implications of dopamine D1 vs. D2 receptors: A 'prepare and select'
      model of the striatal direct vs. indirect pathways.
AB  - The functions of the D1- and D2-dopamine receptors in the basal ganglia have
      remained somewhat enigmatic, with a number of competing theories relating to the
      interactions of the 'direct' and 'indirect pathways'. Computational models have
      been good at simulating properties of the system, but are typically divorced from
      the underlying neural architecture. In this article we propose a new model which
      re-addresses response selection at the level of the basal ganglia. At the core of
      this response selection system the D1 DA receptor-expressing striatal pathways
      'prepare' the set of possible appropriate responses. The D2DR-expressing striatal
      pathways then shape and 'select' from this initial response set framework. This
      article is part of a Special Issue entitled: Ventral Tegmentum & Dopamine. 

PMID- 25062778
TI  - A Review of Teen Dating Violence Prevention Research: What About Hispanic Youth?
AB  - The purpose of this article is to provide a critical review of the literature on
      evidence-based teen dating violence (TDV) prevention programs with a particular
      focus on highlighting gaps in the literature with regard to prevention efforts
      targeting Hispanic teens. The target populations, characteristics, designs, and
      results of TDV prevention studies reported in the scientific literature for the
      last 20 years were reviewed and analyzed according to cultural and contextual
      factors associated with TDV among Hispanic teens. To date, three studies have
      focused on a predominantly Hispanic population with only one study looking at the
      long-term effects of a TDV intervention. There is a growing need to develop and
      evaluate immediate and long-term effects of TDV prevention programs that address
      ethnic pride, acculturation and acculturative stress, familism, and gender norms
      within the context of Hispanic communities (e.g., machismo and marianismo). The
      authors discuss the implications for research, prevention practice, and policy
      regarding TDV prevention for Hispanic teens. 

PMID- 25062779
TI  - Siderophore as a potential plant growth-promoting agent produced by Pseudomonas
      aeruginosa JAS-25.
AB  - Siderophores scavenges Fe(+3) from the vicinity of the roots of plants, and thus
      limit the amount of iron required for the growth of pathogens such as Fusarium
      oxysporum, Pythium ultimum, and Fusarium udum, which cause wilt and root rot
      disease in crops. The ability of Pseudomonas to grow and to produce siderophore
      depends upon the iron content, pH, and temperature. Maximum yield of siderophore
      of 130 MUM was observed at pH 7.0 +/- 0.2 and temperature of 30  degrees C at 30
      h. The threshold level of iron was 50 MUM, which increases up to 150 MUM,
      favoring growth but drastically affecting the production of siderophore by
      Pseudomonas aeruginosa JAS-25. The seeds of agricultural crops like Cicer
      arietinum (chick pea), Cajanus cajan (pigeon pea), and Arachis hypogaea (ground
      nut) were treated with P. aeruginosa JAS-25, which enhanced the seed germination,
      root length, shoot length, and dry weight of chick pea, pigeon pea, and ground
      nut plants under pot studies. The efficient growth of the plants was not only due
      to the biocontrol activity of the siderophore produced by P. aeruginosa JAS-25
      but also may be by the production of indole acetic acid (IAA), which influences
      the growth of the plants as phytohormones.

PMID- 25062780
TI  - Biosynthesis of silver nanoparticles by Bacillus stratosphericus spores and the
      role of dipicolinic acid in this process.
AB  - Seeking for simple, rapid, and environmental-friendly routes to produce metal
      nanoparticles is quite attractive for various biotechnological applications.
      Biological synthesis method of silver nanoparticles has been found very promising
      due to their non-toxicity and simplicity. Here, the spores of Bacillus
      stratosphericus isolated from soil enriched with 30 % H2O2 were used for the
      production of silver nanoparticles. Furthermore, the possible mechanism of silver
      nanoparticle synthesis by the spores was elucidated for the first time. In this
      regard, dipicolinic acid (DPA) was shown to play a critical role as a
      nanoparticle-producing agent. UV-Vis absorption spectroscopy, X-ray diffraction
      technique, energy-dispersive spectroscopy, and transmission electron microscopy
      were used to characterize the nanoparticles. Unlike vegetative cells of B.
      stratosphericus, the spores and the purified DPA were capable of producing
      nanoparticles from silver nitrate (AgNO3). These biogenic nanoparticles, which
      were highly toxic against different pathogenic bacteria, showed mixed structures
      including spherical, triangular, cubic, and hexagonal with the approximate size
      between 2 and 20 nm in diameter. Our results illustrated the role of dipicolinic
      acid as a main factor for the synthesis of nanoparticles by the bacterial spores.

PMID- 25062781
TI  - Phytochemicals as inhibitors of bacterial cell division protein FtsZ: coumarins
      are promising candidates.
AB  - Naturally occurring phytochemicals with reported antibacterial activity were
      screened for their ability to inhibit the bacterial cell division protein
      Escherichia coli FtsZ. Among the representative compounds, coumarins inhibit the
      GTPase and polymerization activities of this protein effectively. Further
      screening with ten coumarin analogs we identified two promising candidates,
      scopoletin and daphnetin. The former is found to inhibit the GTPase activity of
      the protein in a noncompetitive manner. Docking of these coumarins with the
      modeled protein indicate that they bind to T7 loop, which is different from the
      GTP-binding site (active site), thereby supporting the experimental data. Lowest
      binding energy is obtained with scopoletin. 3D QSAR indicates the need for groups
      such as hydroxyl, diethyl, or dimethyl amino in the 7th carbon for enhanced
      activity. None of the coumarins exhibited cytotoxicity against NIH/3T3 and human
      embryonic kidney cell lines. The length of Bacillus subtilis increases in the
      presence of these compounds probably due to the lack of septum formation. Results
      of this study indicate the role of coumarins in halting the first step of
      bacterial cell division process. 

PMID- 25062782
TI  - India to introduce rubella and rotavirus vaccines and inactivated polio vaccine.

PMID- 25062783
TI  - Inhaler reminders improve adherence with controller treatment in primary care
      patients with asthma.
AB  - BACKGROUND: Poor adherence contributes to uncontrolled asthma. Pragmatic
      adherence interventions for primary care settings are lacking. OBJECTIVE: To test
      the effectiveness of 2 brief general practitioner (GP)-delivered interventions
      for improving adherence and asthma control. METHODS: In a 6-month cluster
      randomized 2 * 2 factorial controlled trial, with GP as unit of cluster, we
      compared inhaler reminders and feedback (IRF) and/or personalized adherence
      discussions (PADs) with active usual care alone; all GPs received action plan and
      inhaler technique training. GPs enrolled patients prescribed combination
      controller inhalers, with suboptimal Asthma Control Test (ACT) scores (ACT score
      <=19). Inhaler monitors recorded fluticasone propionate/salmeterol adherence
      (covertly for non-IRF groups) and, in IRF groups, provided twice-daily reminders
      for missed doses, and adherence feedback. PAD GPs received communication training
      regarding adherence. Outcomes collected every 2 months included ACT scores
      (primary outcome) and severe exacerbations. Intention-to-treat mixed-model
      analysis incorporated cluster effect and repeated measures. RESULTS: A total of
      43 GPs enrolled 143 patients with moderate-severe asthma (mean age, 40.3 +/- 15.2
      years; ACT score, 14.6 +/- 3.8; fluticasone propionate dose, 718 +/- 470 MUg).
      Over 6 months, adherence was significantly higher in the IRF group than in non
      IRF groups (73% +/- 26% vs 46% +/- 28% of prescribed daily doses; P < .0001), but
      not between PAD and non-PAD groups. Asthma control improved overall (mean change
      in ACT score, 4.5 +/- 4.9; P < .0001), with no significant difference among
      groups (P = .14). Severe exacerbations were experienced by 11% of the patients in
      IRF groups and 28% of the patients in non-IRF groups (P = .013; after adjustment
      for exacerbation history; P = .06). CONCLUSIONS: Inhaler reminders offer an
      effective strategy for improving adherence in primary care compared with a
      behavioral intervention or usual care, although this may not be reflected in
      differences in day-to-day asthma control.

PMID- 25062784
TI  - Notice of retraction.
AB  - IOS Press has retracted the following publication from its online content:
      [Clinical Hemorheology and Microcirculation 56(1) (2014), 57-66] DOI: 10.3233/CH
      121665. T lymphocytes alterations are associated with oxidized LDL, troponin T,
      white blood cells and C-reactive protein during acute myocardial infarction. -
      The above article published in Vol. 56(1) (2014) is the unrevised version of the
      article that has been published in its correct and revised form in: [Clinical
      Hemorheology and Microcirculation 55(3) (2013), 349-358] DOI: 10.3233/CH-121644

PMID- 25062785
TI  - Author's reply: To PMID 23706354.

PMID- 25062786
TI  - Age- and gender-specific changes of tricuspid annular motion velocities in normal
      hearts.
AB  - BACKGROUND: Mitral annular motion (MAM) and tricuspid annular motion (TAM)
      velocities obtained by pulsed tissue Doppler echocardiography have been used to
      evaluate left ventricular (LV) and right ventricular (RV) functions. Although TAM
      velocity has been clinically applied for evaluating various cardiac diseases, the
      effects of age and gender remain unclear. Therefore, we aimed to determine the
      effects of age and gender on TAM velocity in normal hearts. METHODS: We randomly
      selected 265 subjects (mean age, 59 years; range, 20-89 years) without abnormal
      clinical, electrocardiographic, and echocardiographic findings from a pool of
      subjects who had undergone transthoracic echocardiography. They were classified
      into four age groups: 20-39, 40-59, 60-79, and >80 years. Pulsed wave Doppler was
      applied to obtain MAM velocity of the lateral side and TAM velocity of the RV
      free wall side. The peak systolic (s'), early diastolic (e'), and atrial systolic
      (a') velocities of MAM and TAM were measured in all subjects. RESULTS: While MAM
      s' (r=-0.267, p<0.001) correlated with age, TAM-s' did not (p=0.755). TAM-s' in
      any age groups had no significant gender differences. TAM-e' (r=-0.447, p<0.001)
      and MAM-e' (r=-0.724, p<0.001) correlated with age, respectively. In those aged
      40-59 years, both TAM-e' (p=0.002) and MAM-e' (p=0.048) in females were
      significantly higher than those in males. The gender differences diminished in
      the >=60 years age groups. CONCLUSIONS: There was no age-associated decline in
      TAM-s', while TAM-e' varied with age and gender as did MAM-e'. Although the same
      criteria for the TAM-s' can be used for identifying abnormal RV systolic function
      regardless of age and gender, age and gender differences must be considered when
      one utilizes the TAM-e' for the diagnosis or management of cardiovascular
      disease.

PMID- 25062787
TI  - A systematic review of the efficacy of prophylactic control measures for
      naturally occurring canine leishmaniosis. Part II: topically applied insecticide
      treatments and prophylactic medications.
AB  - The objective of this study was to systematically review the efficacy of
      topically applied insecticide treatments of dogs (impregnated collars, spot-ons),
      and prophylactic medications to prevent natural Leishmania infantum (L. infantum)
      infection in dogs. Randomised controlled trials (RCT), non-randomised clinical
      trials, cohort studies and case-control studies that investigated preventive
      efficacy for natural L. infantum infection in dogs were eligible for inclusion.
      Two review authors independently assessed each study against the inclusion
      criteria, independently extracted relevant data from all included studies and
      assessed the risk of methodological shortcomings in each individual study. The
      odds ratio (OR) and absolute risk reduction (ARR) for dichotomous outcomes and
      mean difference for continuous outcomes were calculated. Meta-analysis was not
      performed due to heterogeneity of the studies identified. The search yielded 937
      articles, from which 84 full text articles were selected for second stage
      screening. Eleven eligible studies were included; four on collars (two RCTs),
      three on spot-ons (two RCTs - one looking at two different dosing regimens),
      three on prophylactic medications (all RCTs) and one on both collars and spot-ons
      summarised in this paper. All of the studies were considered to be at a high risk
      of methodological shortcomings, with the exception of one spot-on study which was
      considered to be at an unclear risk of methodological shortcomings. Deltamethrin
      collars, 65% permethrin, 10% imidacloprid with 50% permethrin spot-ons and
      domperidone prophylactic medication tended to significantly reduce the proportion
      of dogs infected with L. infantum based on either parasitological or serological
      evidence. 

PMID- 25062788
TI  - Use of a multiparty web based videoconference support group for family
      caregivers: Innovative practice.
AB  - This article describes a pilot of a weekly web based videoconference support
      group for five caregivers of persons with dementia. All participants reported
      positive views of the group and videoconference medium. Improvements in caregiver
      anxiety, depression, and physical health scores were observed. Depression scores
      remained the same with difficulties experienced by the caregiver increasing
      slightly. Self-efficacy for controlling upsetting thoughts and responding to
      disruptive behavior improved but worsened slightly for obtaining respite. We
      concluded that web based support was a positive experience for caregivers,
      providing them with an acceptable, feasible, low-cost technological alternative
      to in person support that reduced barriers to attendance by being available in
      homes. 

PMID- 25062789
TI  - Where theory and practice of global health intersect: the developmental history
      of a Canadian global health initiative.
AB  - OBJECTIVE: This paper examines the scope of practice of global health, drawing on
      the practical experience of a global health initiative of the Government of
      Canada--the Teasdale-Corti Global Health Research Partnership Program. A number
      of challenges in the practical application of theoretical definitions and
      understandings of global health are addressed. These challenges are grouped under
      five areas that form essential characteristics of global health: equity and
      egalitarian North-South partnerships, interdisciplinary scope, focus on upstream
      determinants of health, global conceptualization, and global health as an area of
      both research and practice. DESIGN: Information in this paper is based on the
      results of an external evaluation of the program, which involved analysis of
      project proposals and technical reports, surveys with grantees and interviews
      with grantees and program designers, as well as case studies of three projects
      and a review of relevant literature. RESULTS: The philosophy and recent
      definitions of global health represent a significant and important departure from
      the international health paradigm. However, the practical applicability of this
      maturing area of research and practice still faces significant systemic and
      structural impediments that, if not acknowledged and addressed, will continue to
      undermine the development of global health as an effective means to addressing
      health inequities globally and to better understanding, and acting upon, upstream
      determinants of health toward health for all. CONCLUSIONS: While it strives to
      redress global inequities, global health continues to be a construct that is
      promoted, studied, and dictated mostly by Northern institutions and scholars.
      Until practical mechanisms are put in place for truly egalitarian partnerships
      between North and South for both the study and practice of global health, the
      emerging philosophy of global health cannot be effectively put into practice.

PMID- 25062790
TI  - Role of oxidative stress, inflammation, nitric oxide and transforming growth
      factor-beta in the protective effect of diosgenin in monocrotaline-induced
      pulmonary hypertension in rats.
AB  - Pulmonary hypertension is a progressive disease of various origins that is
      associated with right ventricular dysfunction. In the present study, the
      protective effect of diosgenin was investigated in monocrotaline-induced
      pulmonary hypertension in rats. Pulmonary hypertension was induced by a single
      subcutaneous injection of monocrotaline (60 mg/kg). Diosgenin (100 mg/kg) was
      given by oral administration once daily for 3 weeks. At the end of the
      experiment, mean arterial blood pressure, electrocardiography and
      echocardiography were recorded. Rats were then sacrificed and serum was separated
      for determination of total nitrate/nitrite level. Right ventricles and lungs were
      isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha,
      total nitrate/nitrite and transforming growth factor-beta contents.
      Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible
      nitric oxide synthase protein expression were also determined. Moreover,
      histological analysis of pulmonary arteries and cardiomyocyte cross-sectional
      area was performed. Diosgenin treatment provided a significant improvement toward
      preserving hemodynamic changes and alleviating oxidative stress, inflammatory and
      apoptotic markers induced by monocrotaline in rats. Furthermore, diosgenin
      therapy prevented monocrotaline-induced changes in nitric oxide production,
      endothelial and inducible nitric oxide synthase protein expression as well as
      histological analysis. These findings support the beneficial effect of diosgenin
      in pulmonary hypertension induced by monocrotaline in rats.

PMID- 25062791
TI  - Protective effect of melittin against inflammation and apoptosis on
      Propionibacterium acnes-induced human THP-1 monocytic cell.
AB  - Melittin is a cationic, hemolytic peptide that is the main toxic component in the
      venom of the honey bee (Apis mellifera). It has been used in treatment of various
      chronic inflammatory diseases. However, the cellular mechanism and the anti
      apoptotic effect of melittin in Propionibactierium acnes (P. acnes)-induced THP-1
      cells have not been explored. In the present study, we investigated the anti
      inflammatory and anti-apoptotic mechanism by examining the effect of melittin on
      P. acnes-induced THP-1 monocytic cells. THP-1 monocytic cells were stimulated by
      heat-killed P. acnes in the presence of melittin. The expression levels of pro
      inflammatory cytokines, NF-kappaB signaling, caspase family, and PARP signaling
      were measured by ELISA or Western blot analysis. The number of apoptotic cells
      and changes of cell morphology were examined using fluorescence microscopy and
      flow cytometry. Heat-killed P. acnes increased the secretion of pro-inflammatory
      cytokines and cleavage of caspase-3 and -8 in heat-killed P. acnes-induced THP-1
      cells. However, treatment with melittin inhibited the pro-inflammatory cytokines
      and cleavage of the caspase-3 and -8. Moreover, the cleaved PARP appeared after
      8h of heat-killed P. acnes treatment and its cleavage was reduced by melittin
      treatment. These results demonstrate that 1.0*10(7) CFU/ml of heat-killed P.
      acnes induces THP-1 cell apoptosis and secretion of inflammatory cytokines. Also,
      administration of melittin significantly decreases the expression of various
      inflammatory cytokines in heat-killed P. acnes-treated THP-1 monocytic cells. In
      particular, melittin exerts anti-apoptotic effects against 1.0*10(7) CFU/ml of
      heat-killed P. acnes injury to THP-1 cells.

PMID- 25062793
TI  - [Duration of antibiotic treatment after appendicectomy for complicated
      appendicitis].

PMID- 25062792
TI  - Deficits in neuronal cytochrome P450 activity attenuate opioid analgesia but not
      opioid side effects.
AB  - Morphine-like analgesics act on u opioid receptors in the CNS to produce highly
      effective pain relief, but the same class of receptors also mediates non
      therapeutic side effects. The analgesic properties of morphine were recently
      shown to require the activity of a brain neuronal cytochrome P450 epoxygenase,
      but the significance of this pathway for opioid side effects is unknown. Here we
      show that brain P450 activity is not required for three of morphine's major side
      effects (respiratory depression, constipation, and locomotor stimulation).
      Following systemic or intracerebroventricular administration of morphine,
      transgenic mice with brain neuron - specific reductions in P450 activity showed
      highly attenuated analgesic responses as compared with wild-type (control) mice.
      However, brain P450-deficient mice showed normal morphine-induced side effects
      (respiratory depression, locomotor stimulation, and inhibition of intestinal
      motility). Pretreatment of control mice with the P450 inhibitor CC12 similarly
      reduced the analgesia, but not these side effects of morphine. Because activation
      of brain u opioid receptors produces both opioid analgesia and opioid side
      effects, dissociation of the mechanisms for the therapeutic and therapy-limiting
      effects of opioids has important consequences for the development of analgesics
      with reduced side effects and/or limited addiction liability. 

PMID- 25062794
TI  - A full-blooded defence of full-blooded Epicureanism: responses to my critics.

PMID- 25062795
TI  - New strategies in ion channel screening for drug discovery: are there ways to
      improve its productivity?
AB  - INTRODUCTION: From a drug discovery point of view, ion channels are very
      interesting and challenging targets. Over the past decade, great efforts have
      been made in developing platforms for patch clamp-based high-quality screening of
      ion channels in discovering new drug candidates as well for evaluating their
      safety profiles. Indeed, the automated patch clamp (APC) has recently reached the
      data throughput requirements of high-throughput screening (HTS) allowing for new
      screening strategies with ion channel active compounds. AREAS COVERED: This
      editorial article comments on the past and present developments of APC-based drug
      screening. Furthermore, it also looks at the implications of APC technology
      meeting HTS-standards as well as its use in compound safety evaluation. EXPERT
      OPINION: In the imminent future, we will see a paradigm shift in ion channel drug
      screening toward using APC-based platforms for primary drug library screens. This
      way, the redundancy of the drug discovery process and the risk of false-negatives
      could be drastically reduced. Furthermore, cardiac safety can be addressed early,
      avoiding late-phase withdrawals with promising drug candidates. It is our firm
      belief that APC-based ion channel HTS will facilitate the discovery of
      candidates, which otherwise would have not been found, and shorten the drug
      development cycle, saving time and cost.

PMID- 25062797
TI  - Successful treatment of histiocytic sarcoma with induction chemotherapy
      consisting of dose-escalated CHOP plus etoposide and upfront consolidation auto
      transplantation.
AB  - Histiocytic sarcoma (HS) is an extremely rare malignant neoplasm that often
      exhibits an aggressive clinical presentation. In this report, we describe the
      case of a 38-year-old female with advanced-stage HS who was found to have a
      subcutaneous tumor in the left calf and enlarged lymph nodes in the left inguinal
      and internal iliac regions. The subcutaneous tumor and inguinal nodes were
      resected operatively. Immunohistochemistry of the surgical specimens showed that
      the malignant cells stained positive for CD163, CD68, and related markers; a
      diagnosis of HS was established. Following the administration of induction
      chemotherapy consisting of dose-escalated CHOP plus etoposide, the remaining
      internal iliac tumors disappeared. At that point, high-dose chemotherapy with
      autologous stem cell transplantation was performed as consolidation treatment.
      The patient remains alive with no evidence of disease for 30 months post
      treatment. This report provides valuable insight into the treatment of advanced
      HS. 

PMID- 25062799
TI  - Effectiveness of intraoperative indocyanine-green fluorescence angiography during
      inguinal lymph node dissection for skin cancer to prevent postoperative wound
      dehiscence.
AB  - PURPOSE: The incidence of postoperative wound dehiscence following inguinal lymph
      node dissection (ILND) is higher than that in other anatomic regions. To prevent
      wound dehiscence, intraoperative interventions, such as trimming off the ischemic
      part of the flap before wound closure based on indocyanine-green (ICG)
      fluorescence angiography, have been introduced in our institute. This report
      describes a retrospective clinical study of 17 cases, and the objective of the
      study was to evaluate the clinical efficacy of intraoperative intervention using
      ICG fluorescence angiography. METHOD: A total of 17 patients who underwent ILND
      for skin cancer between 2009 and 2013 at our institute were reviewed
      retrospectively, and the significance of variables, including intervention using
      ICG fluorescence angiography, was evaluated using Fisher's exact test. RESULTS:
      There were nine cases of wound dehiscence, and two of these cases required a
      secondary skin graft. Only one case of wound dehiscence developed in the eight
      patients who underwent intervention based on ICG fluorescence angiography. This
      procedure was a significant factor influencing the risk of wound dehiscence (p =
      0.003) in our study. CONCLUSION: Although this was a small case series,
      intraoperative intervention based on ICG fluorescence angiography was effective
      for preventing postoperative wound dehiscence after ILND.

PMID- 25062798
TI  - In-vivo trachea regeneration: fabrication of a tissue-engineered trachea in nude
      mice using the body as a natural bioreactor.
AB  - PURPOSE: To investigate the outcomes of implanting rat decellularized trachea
      scaffold (DTS) between the paravertebral muscles of nude mice using the body as a
      bioreactor for total graft recellularization. METHODS: The tracheas of four rats
      were aseptically resected and decellularized. To assess the efficiency of the
      decellularization procedure, all decellularized scaffolds and native control
      tissues were evaluated with scanning electron microscopy (SEM), DAPI staining,
      DNA quantification, biomechanical analyses and hydroxyproline measurement. They
      were then implanted between the paravertebral muscles of four nude mice. The
      biopsies were precisely evaluated at 1, 3, 6 and 12 months postoperatively for
      tracheal cartilage and soft tissue recellularization by staining for TTF1, CD34,
      S100 and leukocyte common antibody. RESULTS: Hematoxylin and eosin (H&E)
      staining, SEM and the tensile test confirmed the preservation of the tissue
      structure and the biophysical and biochemical properties of the DTS. The present
      study clearly demonstrated that the hydroxyproline content of the DTS was similar
      to that of the native tissue. On the other hand, in biopsy samples obtained after
      12 months, histological evaluation showed superior organization and cell seeding
      in both the cartilage and connective tissues. CONCLUSION: This study demonstrated
      the feasibility of using a natural bioreactor for recellularizing DTS; this may
      have the potential to facilitate homologous transplantation for repairing
      segmental trachea defects.

PMID- 25062800
TI  - Decreased amyloidogenicity caused by mutational modulation of surface properties
      of the immunoglobulin light chain BRE variable domain.
AB  - Amyloid formation by immunoglobulin light chain (LC) proteins is associated with
      amyloid light chain (AL) amyloidosis. Destabilization of the native state of the
      variable domain of the LC (VL) is known to be one of the critical factors in
      promoting the formation of amyloid fibrils. However, determining the key residues
      involved in this destabilization remains challenging, because of the existence of
      a number of intrinsic sequence variations within VL. In this study, we identified
      the key residues for destabilization of the native state of amyloidogenic VL in
      the LC of BRE by analyzing the stability of chimeric mutants of BRE and REI VL;
      the latter immunoglobulin is not associated with AL amyloidosis. The results
      suggest that the surface-exposed residues N45 and D50 are the key residues in the
      destabilization of the native state of BRE VL. Point mutations at the
      corresponding residues in REI VL (K45N, E50D, and K45N/E50D) destabilized the
      native state and increased amyloidogenicity. However, the reverse mutations in
      BRE VL (N45K, D50E, and N45K/D50E) re-established the native state and decreased
      amyloidogenicity. Thus, analyses using chimeras and point mutants successfully
      elucidated the key residues involved in BRE VL destabilization and increased
      amyloidogenic propensity. These results also suggest that the modulation of
      surface properties of wild-type VL may improve their stability and prevent the
      formation of amyloid fibrils. 

PMID- 25062801
TI  - Preventing risk for significant behavior problems through a cognitive-behavioral
      intervention: effects of the tools for getting along curriculum at one-year
      follow-up.
AB  - Efficient and effective social-emotional learning programs increase the
      likelihood of success in school for all students, and particularly for those who
      may develop emotional or behavior problems. In this study, we followed a sub
      sample of students 1 year after their participation in a randomized controlled
      trial of the effects of the Tools for Getting Along (TFGA) curriculum. TFGA is a
      universally delivered, preventive cognitive-behavioral curricular intervention
      designed to improve upper elementary school students' emotional and behavioral
      self-regulation. To determine effects at 1-year follow-up, we assessed 720 out of
      the 1,296 original students across TFGA and control conditions on measures of
      curricular knowledge, teacher-rated executive function and behavior, and student
      reported anger and social problem solving. Findings indicated a continued
      positive effect on curricular knowledge for students taught TFGA relative to
      controls. We also found significant pretest by condition interaction effects on
      teacher reports of skills associated with executive function, including
      inhibitory control and shift (cognitive flexibility), and on teacher reported
      internalizing and externalizing behavior. Specifically, students with poorer
      scores on these measures at pretest benefited from TFGA at follow-up relative to
      comparable students in the control condition. Finally, we found marginally
      significant pretest by condition interaction effects on proactive aggression,
      outward expressions of anger, and the executive function related skills of
      initiating activities and using working memory. Counter to expectations, we found
      negative TFGA effects on student-reported trait anger and anger control.

PMID- 25062802
TI  - Fatty acid metabolism during maturation affects glucose uptake and is essential
      to oocyte competence.
AB  - Fatty acid beta-oxidation (FAO) is essential for oocyte maturation in mice. The
      objective of this study was to determine the effect of etomoxir (a FAO inhibitor;
      100 MUM), carnitine (1 mM), and palmitic acid (1 or 100 MUM) during maturation on
      metabolism and gene expression of the oocyte and cumulus cells, and subsequent
      embryo development in the mouse. Carnitine significantly increased embryo
      development, while there was a decrease in development following maturation with
      100 MUM palmitic acid or etomoxir (P<0.05) treatment. Glucose consumption per
      cumulus-oocyte complex (COC) was decreased after treatment with carnitine and
      increased following etomoxir treatment (P<0.05). Intracellular oocyte lipid
      content was decreased after carnitine or etomoxir exposure (P<0.05). Abundance of
      Slc2a1 (Glut1) was increased after etomoxir treatment in the oocyte and cumulus
      cells (P<0.05), suggesting stimulation of glucose transport and potentially the
      glycolytic pathway for energy production when FAO is inhibited. Abundance of
      carnitine palmitoyltransferase 2 (Cpt2) tended to increase in oocytes (P=0.1)
      after treatment with 100 MUM palmitic acid and in cumulus cells after exposure to
      1 MUM palmitic acid (P=0.07). Combined with carnitine, 1 MUM palmitic acid
      increased the abundance of Acsl3 (P<0.05) and Cpt2 tended to increase (P=0.07) in
      cumulus cells, suggesting FAO was increased during maturation in response to
      stimulators and fatty acids. In conclusion, fatty acid and glucose metabolism are
      related to the mouse COC, as inhibition of FAO increases glucose consumption.
      Stimulation of FAO decreases glucose consumption and lipid stores, positively
      affecting subsequent embryo development, while an overabundance of fatty acid or
      reduced FAO negatively affects oocyte quality. 

PMID- 25062803
TI  - Progesterone improves the maturation of male-induced preovulatory follicles in
      anoestrous ewes.
AB  - The first ovulation induced by male effect in sheep during seasonal anoestrus
      usually results in the development of a short cycle that can be avoided by
      progesterone priming before ram introduction. In elucidating the involvement of
      the hypothalamic-pituitary-gonadal axis in the occurrence of short cycles, the
      effects of progesterone and the time of anoestrus on the development of male
      induced preovulatory follicles were investigated in anoestrous ewes using
      morphological, endocrine and molecular approaches. Ewes were primed with
      progesterone for 2 (CIDR2) or 12 days (CIDR12) and untreated ewes used as
      controls during early (April) and late (June) anoestrus. The duration of
      follicular growth and the lifespan of the male-induced preovulatory follicles
      were prolonged by ~1.6 days in CIDR12 ewes compared with the controls. These
      changes were accompanied by a delay in the preovulatory LH and FSH surges and
      ovulation. Intra-follicular oestradiol concentration and mRNA levels of LHCGR and
      STAR in the granulosa and theca cells of the preovulatory follicles were higher
      in CIDR12 ewes than the control ewes. The expression of mRNA levels of CYP11A1
      and CYP17A1 also increased in theca cells of CIDR12 ewes. CIDR2 ewes gave
      intermediate results. Moreover, ewes ovulated earlier in June than in April,
      without changes in the duration of follicular growth, but these effects were
      unrelated to the lifespan of corpus luteum. Our results give the first evidence
      supporting the positive effect of progesterone priming on the completion of
      growth and maturation of preovulatory follicles induced by male effect in
      seasonal anoestrous ewes, thereby preventing short cycles. 

PMID- 25062805
TI  - Risk factors and prevalence of burnout syndrome in the nursing profession.
AB  - BACKGROUND: The burnout syndrome is beginning to be regarded as an occupational
      illness of high prevalence among nursing in Spain. Individuals suffering from the
      syndrome manifest important health problems. More information about prevalence
      and risk factors for burnout is needed to prevent the syndrome and to determine
      the most appropriate clinical interventions when the disorder appears.
      OBJECTIVES: Burnout levels were evaluated in a group of nurses. The objectives of
      this study were to estimate the prevalence of burnout, to identify the variables
      related to burnout and to propose a risk profile for this syndrome among the
      nursing personnel. SETTING: The study was carried out in public health centers in
      Andalusia (Spain). METHODS: The sample consisted of 676 nursing professionals
      from public health centers. Dependent variables were the three Burnout
      dimensions: emotional exhaustion, depersonalization and personal accomplishment.
      Independent variables were socio-demographic, organizational, personality-related
      variables. RESULTS: The nurses manifested average to high burnout levels. There
      were statistically significant differences in burnout levels associated with the
      following variables: age, gender, marital status, having children, level of
      healthcare, type of work shift, healthcare service areas and conducting
      administrative tasks. Burnout was also associated with personality-related
      variables. CONCLUSIONS: The prevalence of burnout among nursing professionals is
      high. Gender, age, marital status, level of healthcare, work shift and healthcare
      service areas predicted at least one of the dimensions of the syndrome.
      Neuroticism, agreeability, extraversion and conscientiousness are personality
      traits that predict at least two of the dimensions of burnout syndrome in nurses.
      Therefore, personality factors should be considered in any theory of risk
      profiles for developing burnout syndrome in the nursing profession.

PMID- 25062804
TI  - The "neurovascular unit approach" to evaluate mechanisms of dysfunctional
      autoregulation in asphyxiated newborns in the era of hypothermia therapy.
AB  - Despite improvements in obstetrical and neonatal care, and introduction of
      hypothermia as a neuroprotective therapy, perinatal brain injury remains a
      frequent cause of cerebral palsy, mental retardation and epilepsy. The
      recognition of dysfunction of cerebral autoregulation is essential for a real
      time measure of efficacy to identify those who are at highest risk for brain
      injury. This article will focus on the "neurovascular unit" approach to the care
      of asphyxiated neonates and will address 1) potential mechanisms of dysfunctional
      cerebral blood flow (CBF) regulation, 2) optimal monitoring methodology such as
      NIRS (near infrared spectroscopy), and TCD (transcutaneous Doppler), and 3)
      clinical implications of monitoring in the neonatal intensive care setting in
      asphyxiated newborns undergoing hypothermia and rewarming. Critical knowledge of
      the functional regulation of the neurovascular unit may lead to improved ability
      to predict outcomes in real time during hypothermia, as well as differentiate non
      responders who might benefit from additional therapies. 

PMID- 25062806
TI  - Screening and brief intervention delivery in the workplace to reduce alcohol
      related harm: a pilot randomized controlled trial.
AB  - AIM: To explore the feasibility and cost effectiveness of screening and delivery
      of a brief intervention for hazardous drinking employees. METHODS: A pilot
      randomised controlled trial of a brief intervention delivered by an Occupational
      Health nurse versus no delivery of brief intervention (control group) conducted
      in a Local Authority Council (LCA) in the United Kingdom. Changes in quality of
      life and economic indicators were measured by the EQ-5D. RESULTS: 627 employees
      were screened of whom 163 (26.01%) fulfilled the inclusion criteria with a total
      of 57 (35%) agreeing to participate. No significant differences were found
      between the groups for baseline demographics or levels/patterns of alcohol
      consumption. A statistically significant effect was found in the mean AUDIT
      scores over time (F=8.96, p=0.004) but not for group (F=0.017, p=0.896), and no
      significant interaction was found (F=0.148, p=0.702). The cost of each
      intervention was calculated at L12.48, the difference in service costs was
      calculated at L344.50 per person; that is there was a net saving of health and
      other care costs in the intervention group compared to the control group. The
      QALYs fell in both intervention and control groups, the difference -0.002-(
      0.010) yields a net advantage of the intervention of 0.008 QALYs. CONCLUSION: The
      main results from this pilot study suggest that alcohol brief interventions
      delivered in the workplace may offer the potential to reduce alcohol-related harm
      and save public sector resources. A fully powered multi-centre trial is warranted
      to contribute to the current evidence base and explore further the potential of
      alcohol brief interventions in the workplace. In a full trial the recruitment
      method may need to be re-considered.

PMID- 25062807
TI  - Trends in total hip arthroplasty implant utilization in the United States.
AB  - Total hip arthroplasty (THA) implant usage has evolved as experience has been
      gained with newer implant designs. The purpose of this study was to characterize
      trends in THA implant usage between 2001 and 2012. The Orthopedic Research
      Network, which includes 174 hospitals and ~105,000 THA, was used to evaluate
      trends in fixation, bearings, acetabular cup and liner, and femoral head usage.
      In 2012, 93% of THAs were cementless; 56% of THA bearings were metal-HXLPE; and
      35% were ceramic-HXLPE. 99% of acetabular cups were modular. 61% of femoral heads
      were metal, 39% were ceramic, 51% were 36mm, and 28% were 32mm. THA implant usage
      trends favor cementless fixation, metal-on-polyethylene or ceramic-on
      polyethylene bearings, modular acetabular cups, and large diameter femoral heads.

PMID- 25062808
TI  - [Unilateral giant macular scar caused by bilateral congenital toxoplasmosis].

PMID- 25062809
TI  - Organizational commitment and job satisfaction among nurses in Serbia: a factor
      analysis.
AB  - BACKGROUND: One of the basic prerequisites of efficient organizational management
      in health institutions is certainly monitoring and measuring satisfaction of
      employees and their commitment to the health institution in which they work. The
      aim of this article was to identify and test factors that may have a predictive
      effect on job satisfaction and organizational commitment. METHODS: We conducted a
      cross-sectional study that included 1,337 nurses from Serbia. Data were analyzed
      by using exploratory factor analysis, multivariate regressions, and descriptive
      statistics. RESULTS: The study identified three major factors of organizational
      commitment: affective commitment, disloyalty, and continuance commitment. The
      most important predictors of these factors were positive professional
      identification, extrinsic job satisfaction, and intrinsic job satisfaction (p <
      .0001). Predictors significantly affecting both job satisfaction and
      organizational commitment were identified as well; the most important of which
      was positive professional identification (p < .0001). CONCLUSIONS: This study
      identified the main factors affecting job satisfaction and organizational
      commitment of nurses, which formed a good basis for the creation of
      organizational management policy and human resource management policy in health
      institutions in Serbia.

PMID- 25062810
TI  - Cardiac troponin I associated with the development of unrecognized myocardial
      infarctions detected with MRI.
AB  - BACKGROUND: Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are
      sensitive methods to detect subclinical myocardial injury. We sought to
      investigate the relation between plasma concentrations of cTnI measured with a
      high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial
      infarctions (UMIs) detected with LE-MRI. METHODS: After approval from the ethics
      committee and written informed consent were obtained, LE-MRI was performed on 248
      randomly selected community-living 70-year-old volunteers and hs-cTnI was
      determined with a highly sensitive premarket assay. Five years later these
      individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men),
      who did not have a hospital diagnosis of MI, constitute the present study
      population. LE-MR images were analyzed by 2 radiologists independently and in a
      consensus reading, blinded to any information on previous disease or assessments.
      RESULTS: New or larger UMIs were detected in 37 participants during follow-up.
      Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within
      what is considered to be the reference interval, were related to new or larger
      UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln
      transformed cTnI (95% CI, 1.17-3.35; P = 0.010). Plasma concentrations of hs-cTnI
      at 70 years of age were associated with the volumes of the UMIs detected at 75
      years of age (P = 0.028). CONCLUSIONS: hs-cTnI in 70-year-old community-living
      women and men was associated with the development of MRI-detected UMIs within 5
      years.

PMID- 25062811
TI  - Clearance of misfolded and aggregated proteins by aggrephagy and implications for
      aggregation diseases.
AB  - Processing of misfolded proteins is important in order for the cell to maintain
      its normal functioning and homeostasis. Three systems control the quality of
      proteins: chaperone-mediated refolding, proteasomal degradation of ubiquitinated
      proteins, and finally, when the two others fail, aggrephagy, as selective form of
      autophagy, degrades ubiquitin-labelled aggregated cargos. In this route misfolded
      proteins gradually form larger aggregates, aggresomes and they eventually become
      double membrane-wrapped organelles called autophagosomes, which become degraded
      when they fuse to lysosomes, for reuse by the cell. The stages, the main
      molecules participating in the process, and the regulation of aggrephagy are
      discussed here, as is the role of protein aggregation in protein accumulation
      diseases. In particular, we emphasize that both Alzheimer's disease and age
      related macular degeneration, two of the most common pathologies in the aged, are
      characterized by altered protein clearance and deposits. Based on the hypothesis
      that manipulations of autophagy may be potentially useful in these and other
      aggregation-related diseases, we will discuss some promising therapeutic
      strategies to counteract protein aggregates-induced cellular toxicity. 

PMID- 25062812
TI  - Risk control and rational recreation: A qualitative analysis of synthetic drug
      use among young urbanites in China.
AB  - BACKGROUND: To fight against the rapid growth of synthetic drugs, the Chinese
      government has strengthened the controls and regulation, incorporated synthetic
      drugs into the new detoxification system, and changed the inconsistent governance
      of synthetic and traditional drugs. This, however, has not stopped the spread of
      synthetic drugs among young urbanites. While scholars have focused on the
      loopholes and defects of specific drug control regulations, ethnographic
      inquiries illustrate how and why control does not work, or is even resisted by
      young drug users. METHODS: In-depth qualitative interviews were conducted with 28
      individuals aged between 20 and 35, recruited from a cohort of synthetic drug
      users in a Shanghai drug rehabilitation centre. Audio-recorded interviews
      elicited accounts of their daily experiences of drug use as well as their
      perspectives on the impact of the government's new drug control policies.
      RESULTS: The main themes voiced by our respondents include: (1) synthetic drugs
      are not addictive, and are used to feel 'high'; (2) synthetic drugs are used to
      achieve their goals, which are otherwise impossible through mainstream means; (3)
      users are confident that they will be able to manage the use of synthetic drugs
      without harm to themselves; (4) their worries concern administrative punishment
      rather than consequences to health. CONCLUSION: The participants of this study
      did not support the government's attempts to control the use of synthetic drugs.
      They viewed their use as rational recreation under the perceived boundaries of
      'acceptable risks'. Even in the context of severe control, synthetic drugs have
      strong appeal to youths. Drug policy should acknowledge the experiences of users
      and consider the socio-cultural contexts of youth drug-taking. The personal
      experience of participants could help improve the Chinese Drug Control Act and
      regulations.

PMID- 25062813
TI  - A standardized care plan is associated with shorter hospital length of stay in
      patients undergoing pancreaticoduodenectomy.
AB  - BACKGROUND: In this retrospective review, we evaluate a standardized care plan
      (SCP) for patients undergoing pancreaticoduodenectomy, which included selective
      placement of feeding jejunostomy tubes (FJTs) and a perioperative fast-track
      recovery pathway (FTRP). METHODS: A review of 242 patients undergoing
      pancreaticoduodenectomy was completed. Patients treated pre- and post-SCP
      implementation were compared. Univariate comparison followed by multivariable
      linear regression were performed to identify predictors of hospital length of
      stay (HLOS). RESULTS: SCP patients (n = 100) were slightly older but otherwise
      similar to pre-SCP patients (n = 142). FJT placement occurred less frequently in
      SCP patients (38 versus 94%, P < 0.001). All SCP patients were initiated on the
      FTRP. Among SCP patients, an oral diet was introduced earlier (5 versus 8.5 d, P
      < 0.001) and HLOS was shorter (11 versus 13 d, P = 0.015). Readmission rates were
      similar. Following adjustment with linear regression, we confirmed SCP status as
      a predictor of HLOS. To assess SCP components, HLOS was evaluated separately
      based on FTRP status and FJT placement. Although both were highly associated with
      HLOS, neither was independently predictive in multivariable analysis.
      CONCLUSIONS: Implementation of an SCP resulted in shorter HLOS without an
      increase in readmissions. Future studies are necessary to identify specific
      components of SCPs that most influence outcomes.

PMID- 25062814
TI  - The fate of internalized alpha5 integrin is regulated by matrix-capable
      fibronectin.
AB  - BACKGROUND: Assembly of fibronectin matrices is associated with integrin receptor
      turnover and is an important determinant of tissue remodeling. Although it is
      well established that fibronectin is the primary ligand for alpha5beta1 receptor,
      the relationship between fibronectin matrix assembly and the fate of internalized
      alpha5 integrin remains poorly characterized. MATERIALS AND METHODS: To evaluate
      the effect of fibronectin matrix on the fate of internalized alpha5 integrin,
      fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were
      used to track the fate of alpha5 after exposure to exogenous fibronectin.
      RESULTS: In the absence of matrix-capable fibronectin dimer, levels of
      internalized alpha5 decreased rapidly over time. This correlated with a decline
      in total cellular alpha5 and was associated with the ubiquitination of alpha5
      integrin. In contrast, internalized and total cellular alpha5 protein levels were
      maintained when matrix-capable fibronectin was present in the extracellular
      space. Further, we show that ubiquitination and degradation of internalized
      alpha5 integrin in the absence of fibronectin require the presence of two
      specific lysine residues in the alpha5 cytoplasmic tail. CONCLUSIONS: Our data
      demonstrate that alpha5 integrin turnover is dependent on fibronectin matrix
      assembly, where the absence of matrix-capable fibronectin in the extracellular
      space targets the internalized receptor for rapid degradation. These findings
      have important implications for understanding tissue-remodeling processes found
      in wound repair and tumor invasion.

PMID- 25062815
TI  - PREDICT: a diagnostic accuracy study of a tool for predicting mortality within
      one year: who should have an advance healthcare directive?
AB  - BACKGROUND: CARING is a screening tool developed to identify patients who have a
      high likelihood of death in 1 year. AIM: This study sought to validate a modified
      CARING tool (termed PREDICT) using a population of patients presenting to the
      Emergency Department. SETTING/PARTICIPANTS: In total, 1000 patients aged over 55
      years who were admitted to hospital via the Emergency Department between January
      and June 2009 were eligible for inclusion in this study. DESIGN: Data on the six
      prognostic indicators comprising PREDICT were obtained retrospectively from
      patient records. One-year mortality data were obtained from the State Death
      Registry. Weights were applied to each PREDICT criterion, and its final score
      ranged from 0 to 44. Receiver operator characteristic analyses and diagnostic
      accuracy statistics were used to assess the accuracy of PREDICT in identifying 1
      year mortality. RESULTS: The sample comprised 976 patients with a median
      (interquartile range) age of 71 years (62-81 years) and a 1-year mortality of
      23.4%. In total, 50% had >=1 PREDICT criteria with a 1-year mortality of 40.4%.
      Receiver operator characteristic analysis gave an area under the curve of 0.86
      (95% confidence interval: 0.83-0.89). Using a cut-off of 13 points, PREDICT had a
      95.3% (95% confidence interval: 93.6-96.6) specificity and 53.9% (95% confidence
      interval: 47.5-60.3) sensitivity for predicting 1-year mortality. PREDICT was
      simpler than the CARING criteria and identified 158 patients per 1000 admitted
      who could benefit from advance care planning. CONCLUSION: PREDICT was
      successfully applied to the Australian healthcare system with findings similar to
      the original CARING study conducted in the United States. This tool could improve
      end-of-life care by identifying who should have advance care planning or an
      advance healthcare directive.

PMID- 25062816
TI  - Using continuous sedation until death for cancer patients: a qualitative
      interview study of physicians' and nurses' practice in three European countries.
AB  - BACKGROUND: Extensive debate surrounds the practice of continuous sedation until
      death to control refractory symptoms in terminal cancer care. We examined
      reported practice of United Kingdom, Belgian and Dutch physicians and nurses.
      METHODS: Qualitative case studies using interviews. SETTING: Hospitals, the
      domestic home and hospices or palliative care units. PARTICIPANTS: In all, 57
      Physicians and 73 nurses involved in the care of 84 cancer patients. RESULTS: UK
      respondents reported a continuum of practice from the provision of low doses of
      sedatives to control terminal restlessness to rarely encountered deep sedation.
      In contrast, Belgian respondents predominantly described the use of deep
      sedation, emphasizing the importance of responding to the patient's request.
      Dutch respondents emphasized making an official medical decision informed by the
      patient's wish and establishing that a refractory symptom was present.
      Respondents employed rationales that showed different stances towards four key
      issues: the preservation of consciousness, concerns about the potential hastening
      of death, whether they perceived continuous sedation until death as an
      'alternative' to euthanasia and whether they sought to follow guidelines or
      frameworks for practice. CONCLUSION: This qualitative analysis suggests that
      there is systematic variation in end-of-life care sedation practice and its
      conceptualization in the United Kingdom, Belgium and the Netherlands.

PMID- 25062817
TI  - Physiological and proteomic analysis of Lactobacillus casei in response to acid
      adaptation.
AB  - The aim of this study was to investigate the acid tolerance response (ATR) in
      Lactobacillus casei by a combined physiological and proteomic analysis. To
      optimize the ATR induction, cells were acid adapted for 1 h at different pHs, and
      then acid challenged at pH 3.5. The result showed that acid adaptation improved
      acid tolerance, and the highest survival was observed in cells adapted at pH 4.5
      for 1 h. Analysis of the physiological data showed that the acid-adapted cells
      exhibited higher intracellular pH (pHi), intracellular NH4 (+) content, and lower
      inner permeability compared with the cells without adaptation. Proteomic analysis
      was performed upon acid adaptation to different pHs (pH 6.5 vs. pH 4.5) using two
      dimensional electrophoresis. A total of 24 proteins that exhibited at least 1.5
      fold differential expression were identified. Four proteins (Pgk, LacD, Hpr, and
      Galm) involved in carbohydrate catabolism and five classic stress response
      proteins (GroEL, GrpE, Dnak, Hspl, and LCAZH_2811) were up-regulated after acid
      adaptation at pH 4.5 for 1 h. Validation of the proteomic data was performed by
      quantitative RT-PCR, and transcriptional regulation of all selected genes showed
      a positive correlation with the proteomic patterns of the identified proteins.
      Results presented in this study may be useful for further elucidating the acid
      tolerance mechanisms and may help in formulating new strategies to improve the
      industrial performance of this species during acid stress. 

PMID- 25062818
TI  - The niche reduction approach: an opportunity for optimal control of infectious
      diseases in low-income countries?
AB  - BACKGROUND: During the last century, WHO led public health interventions that
      resulted in spectacular achievements such as the worldwide eradication of
      smallpox and the elimination of malaria from the Western world. However, besides
      major successes achieved worldwide in infectious diseases control, most
      elimination/control programs remain frustrating in many tropical countries where
      specific biological and socio-economical features prevented implementation of
      disease control over broad spatial and temporal scales. Emblematic examples
      include malaria, yellow fever, measles and HIV. There is consequently an urgent
      need to develop affordable and sustainable disease control strategies that can
      target the core of infectious diseases transmission in highly endemic areas.
      DISCUSSION: Meanwhile, although most pathogens appear so difficult to eradicate,
      it is surprising to realize that human activities are major drivers of the
      current high rate of extinction among upper organisms through alteration of their
      ecology and evolution, i.e., their "niche". During the last decades, the
      accumulation of ecological and evolutionary studies focused on infectious
      diseases has shown that the niche of a pathogen holds more dimensions than just
      the immune system targeted by vaccination and treatment. Indeed, it is situated
      at various intra- and inter- host levels involved on very different spatial and
      temporal scales. After developing a precise definition of the niche of a
      pathogen, we detail how major advances in the field of ecology and evolutionary
      biology of infectious diseases can enlighten the planning and implementation of
      infectious diseases control in tropical countries with challenging economic
      constraints. SUMMARY: We develop how the approach could translate into applied
      cases, explore its expected benefits and constraints, and we conclude on the
      necessity of such approach for pathogen control in low-income countries.

PMID- 25062820
TI  - Implementation and modeling of a Regional Hub Reception Center during mass
      evacuation operations.
AB  - When developing response plans in the aftermath of a catastrophic incident,
      jurisdictions often fail to conduct the necessary interdisciplinary planning
      needed to fully address the needs across jurisdictional borders. The Purdue
      Homeland Security Institute (PHSI) was selected by the City of Chicago Office of
      Emergency Management and Communications (OEMC) in 2010 to lead an effort to
      address planning across jurisdictional borders during mass evacuations following
      a catastrophic incident. Specifically, PHSI was chosen to lead the effort in
      developing a planning and implementation guide for standing up a conceptual
      Regional Hub Reception Center (RHRC). A major component within the mass
      evacuation and sheltering continuum, the RHRC is designed to provide evacuees
      with quickresponse mass care and emergency assistance while their other needs are
      assessed and appropriate shelter locations are identified. The RHRC also provides
      a central location to leverage governmental, nongovernmental, and private sector
      resources and is the first point in the evacuation, mass care, and sheltering
      concept of operations where more comprehensive support (food, shelter, medical,
      psychological, household pet sheltering, reunification, etc) can be expected.
      PHSI undertook this lead role working within the Illinois-Indiana-Wisconsin (IL
      IN-WI) Combined Statistical Area (CSA) as part of the US Department of Homeland
      Security Regional Catastrophic Planning Grant Program. Coordinating closely with
      the City of Chicago OEMC and IL-IN-WI CSA Regional Catastrophic Planning Team,
      PHSI lead the research effort using resource and capability data compiled from
      all 17 jurisdictions within the IL-IN-WI CSA and validated the RHRC concept using
      three tabletop exercises. Upon completion, the PHSI team published the RHRC
      planning guide complete with procedures and processes that define the roles and
      responsibilities of government, nongovernment organizations, and private sector
      for providing RHRC mass care functions and RHRC capability and capacity
      assessments. This article further examines the potential for using simulation
      modeling as a cost-effective means to rapidly evaluate any facility for potential
      use as a RHRC and to measure and maximize RHRC operational efficiency. Using
      AnyLogic simulation software, PHSI developed a first-ever model of a theoretical
      RHRC capable of simulating, measuring, and manipulating RHRC operations under
      specified conditions/scenarios determined by the emergency management planner.
      Future simulation modeling research promises to promote the Whole Community
      Approach to response and recovery by reinforcing interdisciplinary planning,
      enhancing regional situational awareness, and improving overall jurisdictional
      coordination and synchronization. 

PMID- 25062821
TI  - Emergency planning for people with disabilities and others with access and
      functional needs to ensure inclusiveness.
AB  - Recent investigations and litigation have prompted a shift in the way the field
      of emergency management plans for people with disabilities and others with access
      and functional needs. The purpose of this article is to aid readers in
      understanding some of the legal and practical requirements that may apply to
      jurisdictions' emergency preparedness programs to ensure the ability of plans,
      planning efforts, programs, and services to meet the needs of people with
      disabilities and others with access and functional needs. The cases of
      Communities Actively Living Independent and Free (CALIF) v. City of Los Angeles
      and Brooklyn Center for Independence of the Disabled v. Bloomberg will be used as
      case studies. Note that this is not intended nor should it be construed as legal
      advice. 

PMID- 25062819
TI  - Neighborhood characteristics and sexual intimate partner violence against women
      among low-income, drug-involved New York City residents: results from the IMPACT
      Studies.
AB  - We assessed relations among neighborhood characteristics and sexual intimate
      partner violence against women (SIPVAW), among low-income, drug-involved, women
      (n = 360) and men (n = 670) in New York City between 2005 and 2009. Six percent
      of women (n = 22) and 5% of men (n = 33) reported experiencing and perpetrating
      SIPVAW in the past year with a main partner. In adjusted mixed models among
      women, neighborhood ethnic heterogeneity was significantly negatively associated
      with SIPVAW victimization. In adjusted logistic models among men, neighborhood
      collective efficacy was significantly positively associated with SIPVAW
      perpetration. Novel theoretical frameworks are needed to guide research on
      neighborhoods and partner violence. 

PMID- 25062822
TI  - Emergency evacuation orders: considerations and lessons from Hurricane Sandy.
AB  - This article analyzes the problems surrounding the execution of emergency
      evacuation orders by evaluating Hurricane Sandy and the emergency actions taken
      by the State of New Jersey and the City of Atlantic City New Jersey. The analysis
      provides an overview of the legal authority granting emergency powers to
      governors and mayors to issue evacuation proclamations in addition to an
      evaluation of the New Jersey's emergency evacuation mandate and subsequent
      compliance. The article concludes with provision of planning and preparedness
      recommendations for public managers facing similar hazards, including a
      recommendation for provision of emergency shelter contingencies within the threat
      zone in anticipation of citizen noncompliance evacuation orders. 

PMID- 25062823
TI  - Emergency preparedness and intervention: social work education needs in Israel.
AB  - BACKGROUND: Emergency preparedness and response is gaining increasing global
      attention; numerous conditions contribute to disaster situations including acts
      of terror and war, earthquakes, hurricanes, floods, and tornadoes.
      Internationally, social workers are among the first responders addressing needs
      of children, families, and others affected by traumatic events. OBJECTIVES:
      Assess the level of emergency preparedness and experience of intervening of
      social workers in Negev, Israel. METHODS: Social workers (n = 183) employed by
      public and nonprofit nongovernment organizations throughout the Negev, Israel,
      including population centers of Beer Sheva, Ashkelon, Ashdod, and Sderot were
      queried for this study regarding their experience and training in emergency
      preparedness and interventions. RESULTS: Seventy-six percent of study
      participants had 10 years or less experience; and, the majority (56.1 percent)
      reported they treat trauma and/or post-traumatic stress disorder. Overall, the
      types of populations with whom the participants worked with were children and
      adolescents (65.5 percent), adults (59.6 percent), individuals with drug or
      alcohol dependence (30.1 percent), people with serious mental illness (27.9
      percent), reporting sexual abuse (25.7 percent), those with physical disabilities
      (20.8 percent), and elderly (18.6 percent). Screening and referral were the most
      common services provided, especially by older, more experienced social workers
      who were more likely to have received training to provide disaster mental health
      intervention. Respondents reported disaster intervention training related to work
      with children and families to be most important. CONCLUSION: Further research
      should consider more targeted studies of on emergency preparedness policies for
      vulnerable populations, evaluation of implementation procedures, and training on
      both the professional and community levels among other issues.

PMID- 25062824
TI  - Mobile phone use among Medical Reserve Corps coordinators and volunteers: an
      exploratory study.
AB  - OBJECTIVE: To better understand how mobile phones can be used during emergency
      response, this study identifies a) current mobile phone use among Medical Reserve
      Corps (MRC) volunteers and coordinators in their daily lives and during response;
      b) challenges for mobile phone use during response; and c) areas for capacity
      building. DESIGN: In 2012, 459 MRC volunteers and coordinators responded to a 35
      question survey conducted online through SurveyMonkey. Respondents were asked how
      they use their mobile phones in their daily lives and during response, and how
      they would like to use them during response. Frequencies were calculated using
      SurveyMonkey and Excel. MAIN OUTCOME MEASURES: Respondents reported frequent and
      varied mobile phone use in their daily lives, with 99 percent of respondents
      owning a phone, 82 percent texting, and 87 percent of smartphone owners using
      apps. Although 80 percent of respondents who had been deployed used mobile phones
      during response, use of sophisticated mobile phone features was low; only 10
      percent accessed emergency preparedness apps and 23 percent browsed the Internet
      for emergency response information. Respondents indicated a desire to use more
      features during response, such as emergency preparedness apps (72 percent) and e
      mail to send or receive response instructions (80 percent). CONCLUSION: Results
      indicate that given access to mobile technology and training, emergency
      responders would like to increase their mobile phone use during response.
      Implications of these findings show a need for organizations to improve their
      support of mobile phone use.

PMID- 25062825
TI  - On the effectiveness of shelter-in-place as a measure to reduce harm from
      atmospheric releases.
AB  - Shelter-in-place (SIP) is recommended by numerous entities as a measure to reduce
      harm in the event of a chemical accident or chemical attack taking place in the
      atmosphere. This article, based on solving mass conservation equation for indoor
      hazardous material, examines how effective SIP is to reduce the harm. It is shown
      that SIP can be effective when the shelter's air exchange rate is low and when
      the release duration is short. The effectiveness is strongly affected by the
      hazardous material itself: SIP is more effective for hazardous material with
      higher toxic load exponent. Another finding is that leaving the shelter promptly
      after the event can also be critical. 

PMID- 25062826
TI  - How do emergency managers use social media platforms?
AB  - Social media platforms are increasingly becoming a useful tool for victims,
      humanitarians, volunteers, and the general public to communicate during
      disasters. Research has shown that there are multiple advantages to using social
      media and the applicability of these platforms crosses several different types of
      disasters (human-caused, natural, and terrorist) here in the United States and
      abroad. However, some emergency management agencies have been reluctant to use
      social media as one of their many communications tools. In this study, the
      usefulness of social media for emergency management was examined over a 30-day
      period following a series of tornadoes. Using an observational approach, the
      public posts disseminated from an emergency management agency were analyzed to
      determine how two social media platforms were used. The findings show how
      emergency management agencies could leverage the connectedness of social media to
      reach victims and make unlikely partnerships. 

PMID- 25062827
TI  - Reactive oxygen species regulates expression of iron-sulfur cluster assembly
      protein IscS of Leishmania donovani.
AB  - The cysteine desulfurase, IscS, is a highly conserved and essential component of
      the mitochondrial iron-sulfur cluster (ISC) system that serves as a sulfur donor
      for Fe-S clusters biogenesis. Fe-S clusters are versatile and labile cofactors of
      proteins that orchestrate a wide array of essential metabolic processes, such as
      energy generation and ribosome biogenesis. However, no information regarding the
      role of IscS or its regulation is available in Leishmania, an evolving pathogen
      model with rapidly developing drug resistance. In this study, we characterized
      LdIscS to investigate the ISC system in AmpB-sensitive vs resistant isolates of
      L. donovani and to understand its regulation. We observed an upregulated Fe-S
      protein activity in AmpB-resistant isolates but, in contrast to our expectations,
      LdIscS expression was upregulated in the sensitive strain. However, further
      investigations showed that LdIscS expression is positively correlated with ROS
      level and negatively correlated with Fe-S protein activity, independent of strain
      sensitivity. Thus, our results suggested that LdIscS expression is regulated by
      ROS level with Fe-S clusters/proteins acting as ROS sensors. Moreover, the direct
      evidence of a mechanism, in support of our results, is provided by dose-dependent
      induction of LdIscS-GFP as well as endogenous LdIscS in L. donovani promastigotes
      by three different ROS inducers: H2O2, menadione, and Amphotericin B. We
      postulate that LdIscS is upregulated for de novo synthesis or repair of ROS
      damaged Fe-S clusters. Our results reveal a novel mechanism for regulation of
      IscS expression that may help parasite survival under oxidative stress conditions
      encountered during infection of macrophages and suggest a cross talk between two
      seemingly unrelated metabolic pathways, the ISC system and redox metabolism in L.
      donovani.

PMID- 25062828
TI  - Quality control of oxidatively damaged mitochondrial proteins is mediated by p97
      and the proteasome.
AB  - Protein quality control is essential for maintaining mitochondrial fidelity.
      Proteins damaged by reactive oxygen species necessitate quality control to
      prevent mitochondrial dysfunction connected to aging and neurodegeneration. Here
      we report a role for the AAA ATPase p97/VCP and the proteasome in the quality
      control of oxidized mitochondrial proteins under low oxidative stress as well as
      normal conditions. Proteasomal inhibition and blocking p97-dependent protein
      retrotranslocation interfered with degradation of oxidized mitochondrial
      proteins. Thus, ubiquitin-dependent, p97-, and proteasome-mediated degradation of
      oxidatively damaged proteins plays a key role in maintaining mitochondrial
      fidelity and is likely an important defense mechanism against aging and
      neurodegeneration.

PMID- 25062829
TI  - Novel approach of using a cocktail of designed bacteriophages against gut
      pathogenic E. coli for bacterial load biocontrol.
AB  - BACKGROUND: This study was conducted to explore new approaches of animal
      biocontrol via biological control feed. METHOD: White rats were subjected to 140
      highly lytic designed phages specific against E. coli. Phages were fed via
      drinking water, oral injection, and vegetable capsules. Phage feeding was applied
      by 24 h feeding with 11 d monitoring and 20 d phage feeding and monitoring. Group
      of rats received external pathogenic E. coli and another group did not, namely
      groups A and B. RESULTS: Phage feeding for 20 d via vegetable capsules yielded
      the highest reduction of fecal E. coli, 3.02 and 4.62 log, in rats group A and B
      respectively. Second best, feeding for 20 d via drinking water with alkali
      yielded 2.78 and 4.08 log in rats groups A and B respectively. The peak reduction
      in E. coli output was 5-10 d after phage feeding. Phage control declined after
      10th day of feeding. CONCLUSIONS: The use of cocktail of designed phages
      succeeded in suppressing flora or external E. coli. The phage feed biocontrol is
      efficient in controlling E. coli at the pre-harvest period, precisely at the 6th
      8th day of phage feeding when the lowest E. coli output found.

PMID- 25062830
TI  - Current legal framework and practical aspects of oxygen therapy during air
      travel.
AB  - It is unusual for pulmonologists to be familiar with the European and US
      regulations governing the administration of oxygen during air travel and each
      airline's policy in this respect. This lack of knowledge is in large part due to
      the scarcity of articles addressing this matter in specialized journals and the
      noticeably limited information provided by airlines on their websites. In this
      article we examine the regulations, the policies of some airlines and practical
      aspects that must be taken into account, so that the questions of a patient who
      may need to use oxygen during a flight may be answered satisfactorily.

PMID- 25062831
TI  - Faculty shortages may thwart India's plans for more AIIMS-like institutions in
      every state.

PMID- 25062832
TI  - Structural and antigenic features of the synthetic SF23 peptide corresponding to
      the receptor binding fragment of diphtheria toxin.
AB  - The SF23 peptide corresponding to the receptor binding fragment of diphtheria
      toxin (residues 508-530) has been synthesized. This fragment forming a protruding
      beta hairpin has been chosen because it is the less mutable B-cell epitope.
      Affine chromatography and ELISA show that antibodies from the sera of persons
      infected by toxigenic Corynebacterium diphtheriae and those immunized by
      diphtheria toxoid are able to bind the synthetic SF23 peptide. There are
      antibodies recognizing the SF23 peptide in the serum of horses hyperimmunized
      with diphtheria toxoid. Analysis of circular dichroism spectra show formation of
      beta hairpin by the peptide. Taken together, the results showed that the
      structure of the less mutable epitope of C. diphtheriae toxin was reproduced by
      the short SF23 peptide. Since antibodies against that epitope should block its
      interactions with cellular receptor (heparin-binding epidermal growth factor),
      the SF23 peptide can be considered as a promising candidate for synthetic vaccine
      development. Fluorescence quenching studies showed the existence of chloride and
      phosphate binding sites on the SF23 molecule. Phosphate containing adjuvants
      (aluminum hydroxyphosphate or aluminum hydroxyphosphate sulfate) are recommended
      to increase the SF23 immunogenic properties. 

PMID- 25062833
TI  - Humanized cobra venom factor: structure, activity, and therapeutic efficacy in
      preclinical disease models.
AB  - The complement system is an integral component of both innate and adaptive
      immunity. However, complement is also a pathogenetic factor in many diseases. The
      development of agents for therapeutic complement inhibition is the topic of
      intense investigations by many investigators. We have developed a distinctly
      different therapeutic approach: complement depletion rather than inhibition. This
      approach is based on cobra venom factor (CVF), a C3 analog known to be able to
      safely deplete complement. This manuscript will briefly review the structure and
      activity of CVF, along with its similarities and differences to C3. Exploiting
      the knowledge of the structure/function relationship of CVF and C3, we created
      derivatives of human C3 which display the CVF-like activity of depleting
      complement, referred to as humanized CVF (hCVF). This review describes the
      structure and activity of hCVF, including the important property of not cleaving
      C5. The efficacy of hCVF for therapeutic complement depletion in nine preclinical
      models diseases with complement pathology is reviewed, including reperfusion
      injury, age-related macular degeneration (AMD), paroxysmal nocturnal
      hemoglobinuria (PNH), and immunogenicity of Factor VIII in hemophilia A.
      Complement depletion is characterized by the absence of toxicity, even after
      intra-arterial injection into the pulmonary artery of primates. No immunogenicity
      has been observed. 

PMID- 25062834
TI  - Preface to the special issue for the XXV International Complement Workshop.

PMID- 25062835
TI  - Airway smooth muscle in asthma: linking contraction and mechanotransduction to
      disease pathogenesis and remodelling.
AB  - Asthma is an obstructive airway disease, with a heterogeneous and multifactorial
      pathogenesis. Although generally considered to be a disease principally driven by
      chronic inflammation, it is becoming increasingly recognised that the immune
      component of the pathology poorly correlates with the clinical symptoms of
      asthma, thus highlighting a potentially central role for non-immune cells. In
      this context airway smooth muscle (ASM) may be a key player, as it comprises a
      significant proportion of the airway wall and is the ultimate effector of acute
      airway narrowing. Historically, the contribution of ASM to asthma pathogenesis
      has been contentious, yet emerging evidence suggests that ASM contractile
      activation imparts chronic effects that extend well beyond the temporary effects
      of bronchoconstriction. In this review article we describe the effects that ASM
      contraction, in combination with cellular mechanotransduction and novel
      contraction-inflammation synergies, contribute to asthma pathogenesis. Specific
      emphasis will be placed on the effects that ASM contraction exerts on the
      mechanical properties of the airway wall, as well as novel mechanisms by which
      ASM contraction may contribute to more established features of asthma such as
      airway wall remodelling. 

PMID- 25062836
TI  - Wastewater treatment plant effluents change abundance and composition of ammonia
      oxidizing microorganisms in mediterranean urban stream biofilms.
AB  - Streams affected by wastewater treatment plant (WWTP) effluents are hotspots of
      nitrification. We analyzed the influence of WWTP inputs on the abundance,
      distribution, and composition of epilithic ammonia-oxidizing (AO) assemblages in
      five Mediterranean urban streams by qPCR and amoA gene cloning and sequencing of
      both archaea (AOA) and bacteria (AOB). The effluents significantly modified
      stream chemical parameters, and changes in longitudinal profiles of both NH(4)(+)
      and NO(3)(-) indicated stimulated nitrification activity. WWTP effluents were an
      allocthonous source of both AOA, essentially from the Nitrosotalea cluster, and
      mostly of AOB, mainly Nitrosomonas oligotropha, Nitrosomonas communis, and
      Nitrosospira spp. changing the relative abundance and the natural composition of
      AO assemblages. Under natural conditions, Nitrososphaera and Nitrosopumilus AOA
      dominated AO assemblages, and AOB were barely detected. After the WWTP
      perturbation, epilithic AOB increased by orders of magnitude whereas AOA did not
      show quantitative changes but a shift in population composition to dominance of
      Nitrosotalea spp. The foraneous AOB successfully settled in downstream biofilms
      and probably carried out most of the nitrification activity. Nitrosotalea were
      only observed downstream and only in biofilms exposed to either darkness or low
      irradiance. In addition to other potential environmental limitations for AOA
      distribution, this result suggests in situ photosensitivity as previously
      reported for Nitrosotalea under laboratory conditions.

PMID- 25062837
TI  - A longitudinal analysis of neural regions involved in reading the mind in the
      eyes.
AB  - The ability to perceive social intentions from people's eyes is present from an
      early age, yet little is known about whether this skill is fully developed in
      childhood or that subtle changes may still occur across adolescence. This fMRI
      study investigated the ability to read mental states by using an adapted version
      of the Reading the Mind in the Eyes task within adolescents (aged 12-19 years)
      over a 2-year test-retest interval. This longitudinal setup provides the
      opportunity to study both stability over time as well as age-related changes. The
      behavioral results showed that participants who performed well in the mental
      state condition at the first measurement also performed well at the second
      measurement. fMRI results revealed positive test-retest correlations of neural
      activity in the right superior temporal sulcus and right inferior frontal gyrus
      for the contrast mental state > control, suggesting stability within individuals
      over time. Besides stability of activation, dorsal medial prefrontal cortex
      showed a dip in mid-adolescence for the mental state > control condition and
      right inferior frontal gyrus decreased linearly with age for the mental state >
      control condition. These findings underline changes in the slope of the
      developmental pattern depending on age, even in the existence of relatively
      stable activation in the social brain network. 

PMID- 25062838
TI  - Distracted and down: neural mechanisms of affective interference in subclinical
      depression.
AB  - Previous studies have shown that depressed individuals have difficulty directing
      attention away from negative distractors, a phenomenon known as affective
      interference. However, findings are mixed regarding the neural mechanisms and
      network dynamics of affective interference. The present study addressed these
      issues by comparing neural activation during emotion-word and color-word Stroop
      tasks in participants with varying levels of (primarily subclinical) depression.
      Depressive symptoms predicted increased activation to negative distractors in
      areas of dorsal anterior cingulate cortex (dACC) and posterior cingulate cortex
      (PCC), regions implicated in cognitive control and internally directed attention,
      respectively. Increased dACC activity was also observed in the group-average
      response to incongruent distractors, suggesting that dACC activity during
      affective interference is related to overtaxed cognitive control. In contrast,
      regions of PCC were deactivated across the group in response to incongruent
      distractors, suggesting that PCC activity during affective interference
      represents task-independent processing. A psychophysiological interaction emerged
      in which higher depression predicted more positively correlated activity between
      dACC and PCC during affective interference, i.e. greater connectivity between
      cognitive control and internal-attention systems. These findings suggest that,
      when individuals high in depression are confronted by negative material,
      increased attention to internal thoughts and difficulty shifting resources to the
      external world interfere with goal-directed behavior. 

PMID- 25062839
TI  - God will forgive: reflecting on God's love decreases neurophysiological responses
      to errors.
AB  - In religions where God is portrayed as both loving and wrathful, religious
      beliefs may be a source of fear as well as comfort. Here, we consider if God's
      love may be more effective, relative to God's wrath, for soothing distress, but
      less effective for helping control behavior. Specifically, we assess whether
      contemplating God's love reduces our ability to detect and emotionally react to
      conflict between one's behavior and overarching religious standards. We do so
      within a neurophysiological framework, by observing the effects of exposure to
      concepts of God's love vs punishment on the error-related negativity (ERN)--a
      neural signal originating in the anterior cingulate cortex that is associated
      with performance monitoring and affective responses to errors. Participants
      included 123 students at Brigham Young University, who completed a Go/No-Go task
      where they made 'religious' errors (i.e. ostensibly exhibited pro-alcohol
      tendencies). Reflecting on God's love caused dampened ERNs and worse performance
      on the Go/No-Go task. Thinking about God's punishment did not affect performance
      or ERNs. Results suggest that one possible reason religiosity is generally linked
      to positive well-being may be because of a decreased affective response to errors
      that occurs when God's love is prominent in the minds of believers.

PMID- 25062840
TI  - Randomness increases self-reported anxiety and neurophysiological correlates of
      performance monitoring.
AB  - Several prominent theories spanning clinical, social and developmental psychology
      suggest that people are motivated to see the world as a sensible orderly place.
      These theories presuppose that randomness is aversive because it is associated
      with unpredictability. If this is the case, thinking that the world is random
      should lead to increased anxiety and heightened monitoring of one's actions and
      their consequences. Here, we conduct experimental tests of both of these ideas.
      Participants read one of three passages: (i) comprehensible order, (ii)
      incomprehensible order and (iii) randomness. In Study 1, we examined the effects
      of these passages on self-reported anxiety. In Study 2, we examined the effects
      of the same manipulation on the error-related negativity (ERN), an event-related
      brain potential associated with performance monitoring. We found that messages
      about randomness increased self-reported anxiety and ERN amplitude relative to
      comprehensible order, whereas incomprehensible order had intermediate effects.
      These results lend support to the theoretically important idea that randomness is
      unsettling because it implies that the world is unpredictable. 

PMID- 25062841
TI  - Violence-related PTSD and neural activation when seeing emotionally charged male
      female interactions.
AB  - Post-traumatic stress disorder (PTSD) is a disorder that involves impaired
      regulation of the fear response to traumatic reminders. This study tested how
      women with male-perpetrated interpersonal violence-related PTSD (IPV-PTSD)
      differed in their brain activation from healthy controls (HC) when exposed to
      scenes of male-female interaction of differing emotional content. Sixteen women
      with symptoms of IPV-PTSD and 19 HC participated in this study. During magnetic
      resonance imaging, participants watched a stimulus protocol of 23 different 20 s
      silent epochs of male-female interactions taken from feature films, which were
      neutral, menacing or prosocial. IPV-PTSD participants compared with HC showed (i)
      greater dorsomedial prefrontal cortex (dmPFC) and dorsolateral prefrontal cortex
      (dlPFC) activation in response to menacing vs prosocial scenes and (ii) greater
      anterior cingulate cortex (ACC), right hippocampus activation and lower
      ventromedial prefrontal cortex (vmPFC) activty in response to emotional vs
      neutral scenes. The fact that IPV-PTSD participants compared with HC showed lower
      activity of the ventral ACC during emotionally charged scenes regardless of the
      valence of the scenes suggests that impaired social perception among IPV-PTSD
      patients transcends menacing contexts and generalizes to a wider variety of
      emotionally charged male-female interactions. 

PMID- 25062842
TI  - Electrocortical evidence for rapid allocation of attention to threat in the dot
      probe task.
AB  - Threatening stimuli have been shown to preferentially capture attention using a
      range of tasks and measures. However, attentional bias to threat has not
      typically been found in unselected individuals using behavioral measures in the
      dot-probe task, one of the most common ways of examining attention to threat. The
      present study leveraged event-related potentials (ERPs) in conjunction with
      behavioral measures in the dot-probe task to examine whether more direct measures
      of attention might reveal an attentional bias to threat in unselected
      individuals. As in previous dot-probe studies, we found no evidence of an
      attentional bias to threat using reaction time; additionally, this measure
      exhibited poor internal reliability. In contrast, ERPs revealed an initial shift
      of attention to threat-related stimuli, reflected by the N2pc, which showed
      moderate internal reliability. However, there was no evidence of sustained
      engagement with the threat-related stimuli, as measured by the late positive
      potential (LPP). Together, these results demonstrate that unselected individuals
      do initially allocate attention to threat in the dot-probe task, and further,
      that this bias is better characterized by neural measures of attention than
      traditional behavioral measures. These results have implications for the study of
      attention to threat in both unselected and anxious populations. 

PMID- 25062843
TI  - Social inference deficits in temporal lobe epilepsy and lobectomy: risk factors
      and neural substrates.
AB  - In temporal lobe epilepsy and lobectomy, deficits in emotion identification have
      been found consistently, but there is limited evidence for complex social
      inference skills such as theory of mind. Furthermore, risk factors and the
      specific neural underpinnings of these deficits in this population are unclear.
      We investigated these issues using a comprehensive range of social inference
      tasks (emotion identification and comprehension of sincere, deceitful and
      sarcastic social exchanges) in individuals with temporal lobe epilepsy or
      lobectomy (n = 87). We observed deficits across patient groups which were partly
      related to the presence of mesial temporal lobe sclerosis, early age of seizure
      onset and left lobectomy. A voxel-based morphometry analysis conducted in the pre
      operative group confirmed the importance of the temporal lobe by showing a
      relationship between left hippocampal atrophy and overall social inference
      abilities, and between left anterior neocortex atrophy and sarcasm comprehension.
      These findings are in keeping with theoretical proposals that the hippocampus is
      critical for binding diverse elements in cognitive domains beyond canonical
      episodic memory operations, and that the anterior temporal cortex is a
      convergence zone of higher-order perceptual and emotional processes, and of
      stored representations. As impairments were frequent, we require further
      investigation of this behavioural domain and its impact on the lives of people
      with epilepsy. 

PMID- 25062844
TI  - IGF2BP2 and obesity interaction analysis for type 2 diabetes mellitus in Chinese
      Han population.
AB  - BACKGROUND: The objective of this study was to systematically evaluate the
      contribution of the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
      to type 2 diabetes mellitus (T2DM) and its interaction with obesity to T2DM
      susceptibility. METHODS: To clarify whether IGF2BP2 is an independent risk factor
      for T2DM in Chinese population, we conducted a study with a total of 2,301
      Chinese Han subjects, including 1,166 T2DM patients and 1,135 controls, for the
      genotype of a most common and widely studied polymorphism-rs4402960 of IGF2BP2.
      Genotyping was performed by iPLEX technology. Gene and environment interaction
      analysis was performed by using multiple logistic regression models. RESULTS: The
      repeatedly confirmed association between IGF2BP2 (rs4402960) and T2DM had not
      been replicated in this cohort (P = 0.182). Interestingly, we found that obese
      subjects (body mass index (BMI) >= 28.0 kg/m2) bearing the minor A allele had an
      increased risk to develop T2DM (P = 0.008 for allele analysis and P < 0.001 for
      genotype analysis). CONCLUSIONS: The present study provided data suggesting that
      the wild C allele of IGF2BP2 (rs4402960) had a protective effect against T2DM in
      obese subjects of Chinese Han population.

PMID- 25062845
TI  - Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate
      with the morbidity spectrum of ZBTB20 candidate target genes.
AB  - BACKGROUND: Recently, a number of patients have been described with structural
      rearrangements at 3q13.31, delineating a novel microdeletion syndrome with common
      clinical features including developmental delay and other neurodevelopmental
      disorders (NDD). A smallest region of overlapping deletions (SRO) involved five
      RefSeq genes, including the transcription factor gene ZBTB20 and the dopamine
      receptor gene DRD3, considered as candidate genes for the syndrome. METHODS AND
      RESULTS: We used array comparative genomic hybridization and next-generation mate
      pair sequencing to identify key structural rearrangements involving ZBTB20 in two
      patients with NDD. In a patient with developmental delay, attention-deficit
      hyperactivity disorder, psychosis, Tourette's syndrome and autistic traits, a de
      novo balanced t(3;18) translocation truncated ZBTB20. The other breakpoint did
      not disrupt any gene. In a second patient with developmental delay and autism, we
      detected the first microdeletion at 3q13.31, which truncated ZBTB20 but did not
      involve DRD3 or the other genes within the previously defined SRO. Zbtb20
      directly represses 346 genes in the developing murine brain. Of the 342 human
      orthologous ZBTB20 candidate target genes, we found 68 associated with NDD. Using
      chromatin immunoprecipitation and quantitative PCR, we validated the in vivo
      binding of Zbtb20 in evolutionary conserved regions in six of these genes (Cntn4,
      Gad1, Nrxn1, Nrxn3, Scn2a, Snap25). CONCLUSIONS: Our study links dosage imbalance
      of ZBTB20 to a range of neurodevelopmental, cognitive and psychiatric disorders,
      likely mediated by dysregulation of multiple ZBTB20 target genes, and provides
      new knowledge on the genetic background of the NDD seen in the 3q13.31
      microdeletion syndrome.

PMID- 25062847
TI  - A novel missense mutation in CCDC88C activates the JNK pathway and causes a
      dominant form of spinocerebellar ataxia.
AB  - BACKGROUND: Spinocerebellar ataxias (SCAs) are a group of clinically and
      genetically diverse and autosomal-dominant disorders characterised by
      neurological deficits in the cerebellum. At present, there is no cure for SCAs.
      Of the different distinct subtypes of autosomal-dominant SCAs identified to date,
      causative genes for only a fraction of them are currently known. In this study,
      we investigated the cause of an autosomal-dominant SCA phenotype in a family that
      exhibits cerebellar ataxia and pontocerebellar atrophy along with a global
      reduction in brain volume. METHODS AND RESULTS: Whole-exome analysis revealed a
      missense mutation c.G1391A (p.R464H) in the coding region of the coiled-coil
      domain containing 88C (CCDC88C) gene in all affected individuals. Functional
      studies showed that the mutant form of CCDC88C activates the c-Jun N-terminal
      kinase (JNK) pathway, induces caspase 3 cleavage and triggers apoptosis.
      CONCLUSIONS: This study expands our understanding of the cause of autosomal
      dominant SCAs, a group of heterogeneous congenital neurological conditions in
      humans, and unveils a link between the JNK stress pathway and cerebellar atrophy.

PMID- 25062846
TI  - Human transgenerational responses to early-life experience: potential impact on
      development, health and biomedical research.
AB  - Mammalian experiments provide clear evidence of male line transgenerational
      effects on health and development from paternal or ancestral early-life exposures
      such as diet or stress. The few human observational studies to date suggest (male
      line) transgenerational effects exist that cannot easily be attributed to
      cultural and/or genetic inheritance. Here we summarise relevant studies, drawing
      attention to exposure sensitive periods in early life and sex differences in
      transmission and offspring outcomes. Thus, variation, or changes, in the
      parental/ancestral environment may influence phenotypic variation for better or
      worse in the next generation(s), and so contribute to common, non-communicable
      disease risk including sex differences. We argue that life-course epidemiology
      should be reframed to include exposures from previous generations, keeping an
      open mind as to the mechanisms that transmit this information to offspring.
      Finally, we discuss animal experiments, including the role of epigenetic
      inheritance and non-coding RNAs, in terms of what lessons can be learnt for
      designing and interpreting human studies. This review was developed initially as
      a position paper by the multidisciplinary Network in Epigenetic Epidemiology to
      encourage transgenerational research in human cohorts. 

PMID- 25062848
TI  - Optimal strategies to identify aberrant intra-epithelial lymphocytes in
      refractory coeliac disease.
AB  - INTRODUCTION: Different strategies have been developed to identify those
      refractory celiac disease (RCD) patients who are at risk to develop an
      enteropathy associated T-cell lymphoma (EATL). Flow cytometric analysis of intra
      epithelial lymphocytes (IEL) with an aberrant phenotype is considered the golden
      standard but is not widely available. Immunohistochemistry (IHC) and T-cell
      receptor (TCR) rearrangement studies are commonly available but may lack
      sensitivity and specificity. Here, we compared the three different methods in the
      workup of patients suspected for RCD. METHODS: Duodenal biopsies from control
      patient (n = 5), RCD patients with moderately increased aberrant IEL populations
      (20-50 %: n = 14), and RCD patients with high numbers of aberrant IEL (>50 %: n =
      5) as determined by flow cytometry were analysed by IHC and TCR-gamma chain
      rearrangement analysis. Three pathologists scored the slides independently.
      RESULTS: Sensitivity of IHC and TCR-gamma rearrangement analysis in RCD patients
      with high numbers of aberrant IELs was 100 and 71 %, respectively. RCD patients
      with aberrant cells between 25 and 50 % however, were missed by IHC and TCR in 50
      and 57 % of cases, respectively. In addition, inter-rater reliability analysis of
      the IHC scoring revealed coder-pair Kappa coefficients between 0.28 and 0.85.
      CONCLUSION: Immunohistochemistry and to a lesser extent TCR-gamma clonality
      analysis are sensitive in identifying patients with high numbers of aberrant IEL
      populations, yet miss half of RCD patients with moderately increased numbers. In
      addition, IHC has a high inter-observer variability. Therefore, patients
      suspected for RCD should undergo flow cytometric analysis of the duodenum.

PMID- 25062849
TI  - Infliximab for treatment of granulomatous disease in patients with common
      variable immunodeficiency.
AB  - PURPOSE: Eight to 22 % of common variable immunodeficiency (CVID) patients
      exhibit granulomas of the lungs, spleen, liver, and/or skin. Granulomas can be
      the most medically significant day-to-day problem for CVID patients. Currently,
      there are limited options for treatment of granulomas associated with CVID.
      METHODS: We treated five patients with CVID who exhibited significant clinical
      symptoms secondary to granulomas with infliximab. The patients were selected and
      treated based solely on clinical need and were not otherwise controlled or
      blinded to the therapy. After obtaining baseline studies (labs, spirometry,
      radiology) and excluding infection, they were treated with infliximab 5 mg/kg at
      week 0, 2, 6 and every 4 weeks thereafter. RESULTS: Post treatment improvements
      were seen in all 5 patients with significant clinical responses observed for both
      visceral and cutaneous granulomata. Four of the five patients were maintained on
      infliximab for 5 to 18 months (mean 9.4 months) without adverse reaction or
      increased susceptibility to infection. One patient completed 6 months of therapy
      with improvement of respiratory parameters but discontinued infliximab due to
      joint stiffness and rash that she attributed to the medication. CONCLUSION: In
      our series, infliximab (5 mg/kg monthly) was an effective treatment for cutaneous
      and visceral granulomas in patients with CVID.

PMID- 25062851
TI  - Preparation and evaluation of bovine serum albumin immobilized chiral monolithic
      column for affinity capillary electrochromatography.
AB  - A system of capillary silica monolith with bovine serum albumin (BSA)
      functionalized through two approaches for affinity monolithic capillary
      electrochromatography (AMCEC) was developed. Covalent immobilization conditions
      for two different Schiff base methods, which employed 3-glycidopropyl
      trimethoxysilane (GPTS) and 3-aminopropyl trimethoxysilane (APTS) as starting
      materials, respectively, were investigated to obtain good and stable chiral
      separation. The BSA immobilized silica monoliths were evaluated in terms of
      morphology, electroosmotic flow, retention time, column efficiency and resolution
      of model compound (+/-)-tryptophan. The columns exhibited satisfactory run-to
      run, column-to-column repeatability and maintained their enantioselectivity for
      more than 3months. Both developed methods can baseline separate tryptophan
      enantiomers, whereas shorter retention time, better column efficiency, and
      enantiomeric recognition between two pairs of drug enantiomers (pantoprazole and
      atenolol) were obtained by the GPTS method. 

PMID- 25062850
TI  - A nonradioactive restriction enzyme-mediated assay to detect DNA repair by
      Fe(II)/2-oxoglutarate-dependent dioxygenase.
AB  - The Escherichia coli DNA repair enzyme AlkB belongs to the Fe(II)/2-oxoglutarate
      dependent dioxygenase family. It removes methyl groups from 1-methyl adenine (1
      meA) and 3-methyl cytosine (3-meC) lesions present in single-stranded DNA by
      oxidative decarboxylation. In the current article, we describe an in vitro assay
      that permits rapid detection of AlkB activity. To achieve this, we generated
      methylated oligonucleotide using methyl methanesulfonate and then monitored DNA
      repair using a methylation-sensitive restriction enzyme and novel agarose gel
      electrophoresis system capable of resolving small oligonucleotides. Our approach
      overcomes several drawbacks of NAD(+)-dependent formaldehyde dehydrogenase
      coupled assay and radioisotope-based assay for determining AlkB DNA repair
      activity. 

PMID- 25062852
TI  - A quick signal of starvation induced autophagy: transcription versus post
      translational modification of LC3.
AB  - Autophagy is the major intracellular lysosomal bulk degradation pathway induced
      by nutrient starvation and contributes to the elimination of damaged organelles
      and protein aggregates to recycle building block and is essential for cell
      survival. Microtubule-associated protein 1 light chain 3 (LC3) plays an
      indispensable role in macroautophagy formation and is a molecular marker for the
      process. Here, we show that autophagy increased through quick robust signaling
      from starvation by enhanced levels of LC3, LC3-EGFP (enhanced green fluorescent
      protein) punctate, and bulk proteolysis in rat hepatoma H4-II-E cells and fresh
      rat hepatocytes. After the addition of amino acids to the starvation condition, a
      similar quick signal appeared by significant reduction of the LC3 ratio and bulk
      proteolysis. Interestingly, we observed that post-translational modification of
      LC3 conversion occurred even long before the changes happened in the level of LC3
      mRNA (messenger RNA) expression. A similar coordinated but diverse effect on LC3
      was confirmed by using autophagy and lysosomal inhibitors. These results
      indicated that during starvation the initial robust signal to the cytoplasm can
      induce autophagy activity through modification at the protein level, whereas
      after depleting readily available autophagy proteins the signal goes to the DNA
      transcription level to maintain the autophagy capacity of cells. 

PMID- 25062853
TI  - A nanocomposite/crude extract enzyme-based xanthine biosensor.
AB  - A novel amperometric biosensor for xanthine was developed based on covalent
      immobilization of crude xanthine oxidase (XOD) extracted from bovine milk onto a
      hybrid nanocomposite film via glutaraldehyde. Toward the preparation of the film,
      a stable colloids solution of core-shell Fe3O4/polyaniline nanoparticles
      (PANI/Fe3O4 NPs) was dispersed in solution containing chitosan (CHT) and H2PtCl6
      and electrodeposited over the surface of a carbon paste electrode (CPE) in one
      step. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR)
      spectrophotometry, cyclic voltammetry (CV), and electrochemical impedance
      spectroscopy (EIS) were used for characterization of the electrode surface. The
      developed biosensor (XOD/CHT/Pt NPs/PANI/Fe3O4/CPE) was employed for
      determination of xanthine based on amperometric detection of hydrogen peroxide
      (H2O2) reduction at -0.35V (vs. Ag/AgCl). The biosensor exhibited a fast response
      time to xanthine within 8s and a linear working concentration range from 0.2 to
      36.0MUM (R(2)=0.997) with a detection limit of 0.1MUM (signal/noise [S/N]=3). The
      sensitivity of the biosensor was 13.58MUAMUM(-1)cm(-2). The apparent Michaelis
      Menten (Km) value for xanthine was found to be 4.7MUM. The fabricated biosensor
      was successfully applied for measurement of fish and chicken meat freshness,
      which was in agreement with the standard method at the 95% confidence level. 

PMID- 25062854
TI  - Kinase signalling in Huntington's disease.
AB  - Alterations in numerous signal transduction pathways and aberrant activity of
      specific kinases have been identified in multiple cell and mouse models of
      Huntington's disease (HD), as well as in human HD brain. The balance and
      integration of a network of kinase signalling pathways is paramount for the
      regulation of a wide range of cellular and physiological processes, such as
      proliferation, differentiation, inflammation, neuronal plasticity and apoptosis.
      Unbalanced activity within these pathways provides a potential mechanism for many
      of the pathological phenotypes associated with HD, such as transcriptional
      dysregulation, inflammation and ultimately neurodegeneration. The
      characterisation of aberrant kinase signalling regulation in HD has been
      inconsistent and may be a result of failure to consider integration between
      multiple signalling pathways, as well as alterations that may occur over time
      with both age and disease progression. Collating the information about the effect
      of mHTT on signalling pathways demonstrates that it has wide ranging effects on
      multiple pro- and anti-apoptotic kinases, resulting in the dysregulation of
      numerous complex interactions within a dynamic network. 

PMID- 25062855
TI  - Unawareness of deficits in Huntington's disease.
AB  - People with Huntington's disease (HD) may show reduced awareness of physical and
      mental changes in themselves. This article reviews the evidence for loss of
      awareness (anosognosia) in an attempt to elucidate its characteristics and
      possible underlying mechanisms. It is shown that defective awareness occurs
      across domains. People with HD may under-report the presence or severity of
      involuntary movements, under-estimate cognitive impairment and deny behavioural
      change. Nevertheless, awareness is not all or none. Moreover, it may be affected
      differentially for different symptom domains and emerge at different stages of
      disease, raising the possibility of distinct contributory mechanisms. Findings of
      an inverse relationship between insight and severity of disease suggest that
      cognitive impairment, in particular executive dysfunction, may be an important
      contributory factor. Evidence has accrued to support this argument. However,
      cognitive impairment cannot fully account for patients' lack of awareness of
      involuntary movements. Findings that patients accurately report consequences but
      not the experience of involuntary movements, and better acknowledge their
      presence when watching videotapes of themselves suggests that physiological
      factors play an important role. The putative role of denial as a coping mechanism
      is discussed. Recognition by clinicians of deficient self-awareness is crucial
      because of its implications for diagnosis and optimal clinical management of HD. 

PMID- 25062856
TI  - Tetrabenazine, depression and suicide: good news.

PMID- 25062857
TI  - Does interval between screening and baseline matter in HD cognitive clinical
      trials?
AB  - BACKGROUND: "Practice effects" (PE), or performance improvements due to prior
      exposure to testing, are known to confound cognitive test results, particularly
      when short intervals occur between two test sessions. OBJECTIVE: We examined two
      subsamples with short or long re-test intervals from a recent clinical trial.
      METHODS: Thirty-four non-depressed adults with mild Huntington Disease (HD)
      participated. Three cognitive tests were administered at screening and again at
      baseline, before active treatment randomization. Half the sample had a 24-hour
      retest interval while the other half was >6-days. RESULTS: The two groups
      differed on demographic/clinical factors (age, Total Motor Score and Total
      Functional Capacity). After controlling for age and motor score, PE differences
      were found on three of the five UHDRS cognitive tests: the longer interval group
      showed larger PE on Symbol-Digit Modalities and Stroop color, while the rapid
      interval group had larger PE on Stroop interference. Controlling for screening
      cognitive performance yielded similar results. CONCLUSIONS: Length of interval
      between screening and baseline visits and level of disease severity may influence
      stability of UHDRS cognitive test results in clinical trials in HD.

PMID- 25062858
TI  - Cognitive deficits in transgenic and knock-in HTT mice parallel those in
      Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is characterized not only by severe motor
      deficits but also by early cognitive dysfunction that significantly increases the
      burden of the disease for patients and caregivers. Considerable efforts have
      concentrated, therefore, on the assessment of cognitive deficits in some HD mouse
      models. However, many of these models that exhibit cognitive deficits also have
      contemporaneous serious motor deficits, confounding interpretation of cognitive
      decline. OBJECTIVE: The BACHD and zQ175 mouse models present a more slowly
      progressing disease phenotype in both motor and cognitive domains, and might
      therefore offer a better opportunity to measure cognitive decline over a longer
      timeframe; such models could be useful in screening therapeutic compounds. In
      order to better define the cognitive impairments evident in BACHD and zQ175 HD
      mice, both were tested in an instrumental touchscreen visual discrimination assay
      designed to assess discrimination learning and cognitive flexibility. METHODS:
      BACHD and zQ175 mice, as well as their WT controls were tested for their ability
      to discriminate two complex visual stimuli. Following this discrimination phase,
      the reinforcement contingencies were reversed and the previously incorrect
      stimulus became the correct stimulus. In a final, third phase of testing, two
      novel stimuli were introduced and mice were required to undergo a second round of
      discrimination testing with these stimuli. RESULTS: Our results show that
      learning during the discrimination phase was similar between the WT and BACHD
      mice. In contrast, the zQ175 at 26 weeks of age showed decreased accuracy over
      the last 10 days of discrimination, compared to WT controls. During subsequent
      reversal and novel stimuli phases, both BACHD and zQ175 mice exhibited
      significant deficits compared to WT controls. CONCLUSIONS: Our results suggest
      that the BACHD, and for the first time, zQ175 HD models exhibit cognitive
      inflexibility and psychomotor slowing, a phenotype that is consistent with
      cognitive symptoms described in HD patients.

PMID- 25062859
TI  - Assessment of chloroquine treatment for modulating autophagy flux in brain of WT
      and HD mice.
AB  - BACKGROUND: Increasing mutant huntingtin (mHTT) clearance through the autophagy
      pathway may be a way to treat Huntington's disease (HD). Tools to manipulate and
      measure autophagy flux in brain in vivo are not well established. OBJECTIVE: To
      examine the in vivo pharmacokinetics and pharmacodynamics of the lysosomal
      inhibitor chloroquine (CQ) and the levels of selected autophagy markers to
      determine usefulness of CQ as a tool to study autophagy flux in brain. METHODS:
      Intraperitoneal injections of CQ were administered to WT and HD(Q175/Q175) mice.
      CQ levels were measured by LC-MS/MS in WT brain, muscle and blood at 4 to 24
      hours after the last dose. Two methods of tissue preparation were used to detect
      by Western blot levels of the macroautophagy markers LC3 II and p62, the
      chaperone mediated autophagy receptor LAMP-2A and the late endosome/lysosomal
      marker RAB7. RESULTS: Following peripheral administration, CQ levels were highest
      in muscle and declined rapidly between 4 and 24 hours. In the brain, CQ levels
      were greater in the cortex than striatum, and levels persisted up to 24 hours
      post-injection. CQ treatment induced changes in LC3 II and p62 that were variable
      across regions and tissue preparations. HD(Q175/Q175) mice exposed to CQ had
      variable but diminished levels of LC3 II, p62 and LAMP-2A, and increased levels
      of RAB7. Higher levels of mHTT were found in the membrane compartment of CQ
      treated HD mice. CONCLUSION: Our findings suggest that the response of brain to
      CQ treatment, a blocker of autophagy flux, is variable and not as robust as it
      has been demonstrated in vitro, suggesting that CQ treatment has limitations for
      modulating autophagy flux in vivo. Alternative methods, compounds, and
      technologies need to be developed to further investigate autophagy flux in vivo,
      especially in the brain.

PMID- 25062860
TI  - Optimising mobility outcome measures in Huntington's disease.
AB  - BACKGROUND: Many of the performance-based mobility measures that are currently
      used in Huntington's disease (HD) were developed for assessment in other
      neurological conditions such as stroke. OBJECTIVE: We aimed to assess the
      individual item-response of commonly used performance-based mobility measures,
      with a view to optimizing the scales for specific application in Huntington's
      Disease (HD). METHOD: Data from a larger multicentre, observational study were
      used. Seventy-five people with HD (11 pre-manifest & 64 manifest) were assessed
      on the Six-Minute Walk Test, 10-Meter Walk Test, Timed "Up & Go" Test (TUG), Berg
      Balance Scale (BBS), Physical Performance Test (PPT), Four Square Step Test, and
      Tinetti Mobility Test (TMT). The Unified Huntington's Disease Rating Scale
      (UHDRS) Total Motor Score, Functional Assessment Scale and Total Functional
      Capacity scores were recorded, alongside cognitive measures. Standard regression
      analysis was used to assess predictive validity. Individual item responses were
      investigated using a sequence of approaches to allow for gradual removal of items
      and the subsequent creation of shortened versions. Psychometric properties
      (reliability and discriminant ability) of the shortened scales were assessed.
      RESULTS: TUG (beta 0.46, CI 0.20-3.47), BBS (beta -0.35, CI -2.10-0.14), and TMT
      (beta -0.45, CI -3.14-0.64) were good disease-specific mobility measures. PPT was
      the best measure of functional performance (beta 0.42, CI 0.00-0.43 for TFC &
      beta 0.57 CI 0.15-0.81 for FAS). Shortened versions of BBS and TMT were developed
      based on item analysis. The resultant BBS and TMT shortened scales were reliable
      for use in manifest HD. ROC analysis showed that shortened scales were able to
      discriminate between manifest and pre-manifest disease states. DISCUSSION: Our
      data suggests that the PPT is appropriate as a general measure of function in
      individuals with HD, and we have identified shortened versions of the BBS and TMT
      that measure the unique gait and balance impairments in HD. These scales,
      alongside the TUG, may therefore be important measures to consider in future
      clinical trials.

PMID- 25062861
TI  - A pilot study of virtual visits in Huntington disease.
AB  - BACKGROUND: Virtual visits through web-based video conferencing can increase
      access to specialty care for individuals with Huntington disease (HD) and
      facilitate research participation. OBJECTIVE: To determine the feasibility of
      conducting virtual visits directly into the homes of individuals with HD, to
      assess the reliability of conducting remote versus in-person motor assessments,
      and to determine the test-retest reliability of conducting motor assessments
      remotely. METHODS: Individuals with mild to moderate HD underwent baseline in
      person clinic assessments and completed a HD care survey. Participants were
      randomized to receive three virtual visits from one of two physicians over four
      months that included a modified Unified Huntington's Disease Rating Scale motor
      examination (excluding rigidity and balance assessments) via web-based video
      conferencing. Intraclass coefficients (ICC) were calculated to determine the
      level of agreement between remote and in-person assessments. Participants also
      completed a survey on their interest in telemedicine. RESULTS: Thirteen
      individuals underwent baseline assessments, eleven (85%) participants completed
      at least one virtual visit, and 27 (82%) of 33 total virtual visits were
      completed. Remote motor scores demonstrated good reliability (ICC = 0.78; n = 11)
      compared to in-person motor scores. Test-retest reliability of motor scores
      conducted remotely was excellent (ICC = 0.90; n = 11). Participants expressed
      moderate future interest in using virtual visits to participate in research and
      to receive care. CONCLUSION: In this pilot study, virtual visits into the home
      were feasible and reliable for conducting motor assessments in HD. Larger scale
      studies need to confirm and generalize these findings to a broader population of
      participants.

PMID- 25062862
TI  - The potential of composite cognitive scores for tracking progression in
      Huntington's disease.
AB  - BACKGROUND: Composite scores derived from joint statistical modelling of
      individual risk factors are widely used to identify individuals who are at
      increased risk of developing disease or of faster disease progression. OBJECTIVE:
      We investigated the ability of composite measures developed using statistical
      models to differentiate progressive cognitive deterioration in Huntington's
      disease (HD) from natural decline in healthy controls. METHODS: Using
      longitudinal data from TRACK-HD, the optimal combinations of quantitative
      cognitive measures to differentiate premanifest and early stage HD individuals
      respectively from controls was determined using logistic regression. Composite
      scores were calculated from the parameters of each statistical model. Linear
      regression models were used to calculate effect sizes (ES) quantifying the
      difference in longitudinal change over 24 months between premanifest and early
      stage HD groups respectively and controls. ES for the composites were compared
      with ES for individual cognitive outcomes and other measures used in HD research.
      The 0.632 bootstrap was used to eliminate biases which result from developing and
      testing models in the same sample. RESULTS: In early HD, the composite score from
      the HD change prediction model produced an ES for difference in rate of 24-month
      change relative to controls of 1.14 (95% CI: 0.90 to 1.39), larger than the ES
      for any individual cognitive outcome and UHDRS Total Motor Score and Total
      Functional Capacity. In addition, this composite gave a statistically significant
      difference in rate of change in premanifest HD compared to controls over 24
      months (ES: 0.24; 95% CI: 0.04 to 0.44), even though none of the individual
      cognitive outcomes produced statistically significant ES over this period.
      CONCLUSIONS: Composite scores developed using appropriate statistical modelling
      techniques have the potential to materially reduce required sample sizes for
      randomised controlled trials.

PMID- 25062863
TI  - The co-occurrence of Alzheimer's disease and Huntington's disease: a
      neuropathological study of 15 elderly Huntington's disease subjects.
AB  - BACKGROUND: Dementia is a common feature in both Huntington's disease (HD) and
      Alzheimer's disease (AD), as well as in the general elderly population. Few
      studies have examined elderly HD patients with dementia for neuropathologic
      evidence of both HD and AD. OBJECTIVE: We present neuropathological findings in a
      retrospective case series of 15 elderly HD patients (ages 60-91 years), 11 of
      whom had prominent clinical dementia. METHODS: Post-mortem brain tissue was
      examined and stained for evidence of both HD and AD including Vonsattel grading
      and Htt-repeat expansion, Bielskowsky, tau, beta amyloid, and TDP43
      immunostaining. RESULTS: Mean age at death was 76.8 years, mean disease duration
      was 18.6 years, and mean CAG repeat expansion was 42. Evidence of AD in addition
      to HD pathology was present in 9 of 11 (82%) patients with prominent dementia,
      suggesting that AD may be more commonly co-occurring with HD than previously
      appreciated. Two patients had only HD as the basis of dementia and four patients
      did not have prominent dementia. One patient with marked parkinsonian features
      was not L-dopa responsive and had no substantia nigra Lewy bodies at autopsy.
      CONCLUSIONS: Our study suggests that AD may frequently contribute to cognitive
      decline in elderly HD patients which complicates the assessment and management of
      such individuals. Further study is needed to determine if there is a higher
      incidence of AD in persons with HD compared to the general population. In
      addition, our series includes one HD patient whose clinical features masqueraded
      as Parkinson's disease but was not responsive to levodopa therapy.

PMID- 25062864
TI  - Generality of a congruity effect in judgements of relative order.
AB  - The judgement of relative order (JOR) procedure is used to investigate serial
      order memory. Measuring response times, the wording of the instructions (whether
      the earlier or the later item was designated as the target) reversed the
      direction of search in subspan lists (Chan, Ross, Earle, & Caplan Psychonomic
      Bulletin & Review, 16(5), 945-951, 2009). If a similar congruity effect applied
      to above-span lists and, furthermore, with error rate as the measure, this could
      suggest how to model order memory across scales. Participants performed JORs on
      lists of nouns (Experiment 1: list lengths = 4, 6, 8, 10) or consonants
      (Experiment 2: list lengths = 4, 8). In addition to the usual distance, primacy,
      and recency effects, instructions interacted with serial position of the later
      probe in both experiments, not only in response time, but also in error rate,
      suggesting that availability, not just accessibility, is affected by
      instructions. The congruity effect challenges current memory models. We fitted
      Hacker's (Journal of Experimental Psychology: Human Learning and Memory, 6(6),
      651-675, 1980) self-terminating search model to our data and found that a switch
      in search direction could explain the congruity effect for short lists, but not
      longer lists. This suggests that JORs may need to be understood via direct-access
      models, adapted to produce a congruity effect, or a mix of mechanisms.

PMID- 25062866
TI  - Effect of surface charge on the brain delivery of nanostructured lipid carriers
      in situ gels via the nasal route.
AB  - The aim of this study was to investigate the influence of the nanocarrier surface
      charge on brain delivery of a model hydrophilic drug via the nasal route. Anionic
      and cationic nanostructured lipid carriers (NLCs) were prepared and optimized for
      their particle size and zeta potential. The optimum particles were incorporated
      in poloxamer in situ gels and their in vivo behavior was studied in the plasma
      and brain after administration to rats. Optimum anionic and cationic NLCs of size
      <200 nm and absolute zeta potential value of ~ 34 mV were obtained. Toxicity
      study revealed mild to moderate reversible inflammation of the nasal epithelium
      in rats treated with the anionic NLCs (A7), and destruction of the lining mucosal
      nasal epithelium in rats treated with the cationic NLCs (C7L). The absolute
      bioavailability of both drug loaded anionic and cationic NLCs in situ gels was
      enhanced compared to that of the intranasal solution (IN) of the drug with values
      of 44% and 77.3%, respectively. Cationic NLCs in situ gel showed a non
      significant higher Cmax (maximum concentration) in the brain compared to the
      anionic NLCs in situ gel. Anionic NLCs in situ gel gave highest drug targeting
      efficiency in the brain (DTE%) with a value of 158.5 which is nearly 1.2 times
      that of the cationic NLCs in situ gel.

PMID- 25062865
TI  - Radiation-induced myeloid leukemia in murine models.
AB  - The use of radiation therapy is a cornerstone of modern cancer treatment. The
      number of patients that undergo radiation as a part of their therapy regimen is
      only increasing every year, but this does not come without cost. As this number
      increases, so too does the incidence of secondary, radiation-induced neoplasias,
      creating a need for therapeutic agents targeted specifically towards incidence
      reduction and treatment of these cancers. Development and efficacy testing of
      these agents requires not only extensive in vitro testing but also a set of
      reliable animal models to accurately recreate the complex situations of radiation
      induced carcinogenesis. As radiation-induced leukemic progression often involves
      genomic changes such as rearrangements, deletions, and changes in methylation,
      the laboratory mouse Mus musculus, with its fully sequenced genome, is a powerful
      tool in cancer research. This fact, combined with the molecular and physiological
      similarities it shares with man and its small size and high rate of breeding in
      captivity, makes it the most relevant model to use in radiation-induced leukemia
      research. In this work, we review relevant M. musculus inbred and F1 hybrid
      animal models, as well as methods of induction of radiation-induced myeloid
      leukemia. Associated molecular pathologies are also included. 

PMID- 25062867
TI  - The anti-epileptic drug substance vigabatrin inhibits taurine transport in
      intestinal and renal cell culture models.
AB  - The GABA-mimetic anti-epileptic drug substance vigabatrin is used against
      infantile spasms. In vitro and in vivo experiments have shown that vigabatrin is
      transported via the proton coupled amino acid transporter (PAT1) mediating at
      least parts of the intestinal absorption of the drug. However, such evidence does
      not preclude the involvement of other transporters. The aim of the present study
      was, therefore, to investigate if vigabatrin interacts with taurine transport.
      The uptake of taurine was measured in intestinal human Caco-2 and canine MDCK
      cell monolayers in the absence or presence of amino acids such as GABA and
      vigabatrin. Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to
      34 +/- 3 and 53 +/- 2%, respectively, at a concentration of 30 mM. In Caco-2
      cells the uptake of vigabatrin under neutral pH conditions is concentration
      dependent and saturable with a Km-value of 27 mM (log Km is 1.43 +/- 0.09). In
      conclusion, the present study shows that vigabatrin was able to inhibit the
      uptake of taurine in intestinal and renal cell culture models. Furthermore,
      uptake of vigabatrin in Caco-2 cells under neutral pH conditions was
      concentration-dependent and saturable and suggesting that vigabatrin partly was
      transported via a taurine transporter, which is likely to be TauT.

PMID- 25062868
TI  - Improving the power of genetic association tests with imperfect phenotype derived
      from electronic medical records.
AB  - To reduce costs and improve clinical relevance of genetic studies, there has been
      increasing interest in performing such studies in hospital-based cohorts by
      linking phenotypes extracted from electronic medical records (EMRs) to genotypes
      assessed in routinely collected medical samples. A fundamental difficulty in
      implementing such studies is extracting accurate information about disease
      outcomes and important clinical covariates from large numbers of EMRs. Recently,
      numerous algorithms have been developed to infer phenotypes by combining
      information from multiple structured and unstructured variables extracted from
      EMRs. Although these algorithms are quite accurate, they typically do not provide
      perfect classification due to the difficulty in inferring meaning from the text.
      Some algorithms can produce for each patient a probability that the patient is a
      disease case. This probability can be thresholded to define case-control status,
      and this estimated case-control status has been used to replicate known genetic
      associations in EMR-based studies. However, using the estimated disease status in
      place of true disease status results in outcome misclassification, which can
      diminish test power and bias odds ratio estimates. We propose to instead directly
      model the algorithm-derived probability of being a case. We demonstrate how our
      approach improves test power and effect estimation in simulation studies, and we
      describe its performance in a study of rheumatoid arthritis. Our work provides an
      easily implemented solution to a major practical challenge that arises in the use
      of EMR data, which can facilitate the use of EMR infrastructure for more
      powerful, cost-effective, and diverse genetic studies. 

PMID- 25062869
TI  - Clinical validation of the international consensus diagnostic criteria and
      algorithms for autoimmune pancreatitis: combined IAP and KPBA meeting 2013
      report.
AB  - There have been great developments in the diagnosis and treatment of autoimmune
      pancreatitis (AIP) in the last decade. Most significantly, the international
      consensus diagnostic criteria (ICDC) proposed in 2011 were the first attempt to
      provide unified diagnostic criteria incorporating most features of the previously
      existing national criteria. However, the ICDC have not yet been prospectively
      validated using evidence-based studies since their introduction. An international
      symposium on the diagnosis of AIP was held in Seoul, South Korea on September 6,
      2013, in cooperation with the International Association of Pancreatology and the
      Korean Pancreatobiliary Association meeting. In contrast to other symposia in the
      past, which had primarily focused on the diagnostic criteria themselves, expert
      panels in this symposium discussed how the diagnostic criteria and algorithms had
      been embraced in clinical settings to diagnose AIP in each country and conducted
      a comprehensive evaluation of these criteria and algorithms. It was acknowledged
      that there was a room for improvement in the ICDC and their algorithms and that
      further modifications might be required in the future. Prospective clinical
      validation in larger series is needed for confirmation.

PMID- 25062870
TI  - Current concepts of the role of abdominal compartment syndrome in acute
      pancreatitis - an opportunity or merely an epiphenomenon.
AB  - The association of acute pancreatitis (AP) with intra-abdominal hypertension
      (IAH) and abdominal compartment syndrome (ACS) has only recently been recognized.
      The detrimental effects of raised intra-abdominal pressure in cardiovascular,
      pulmonary and renal systems have been well established. Although IAH was
      associated with a higher APACHE II score and multi-organ dysfunction syndrome
      (MODS) in severe acute pancreatitis, a causal relationship between ACS and MODS
      in SAP is yet to be established. It is therefore debatable whether IAH is a
      phenomenon causative of organ failure or an epiphenomenon seen in conjunction
      with other organ dysfunction. This review systemically examines the
      pathophysiological basis and clinical relevance of ACS in AP and summarizes all
      the available evidence in its management.

PMID- 25062871
TI  - Endotherapy in symptomatic pancreas divisum: a systematic review.
AB  - Pancreas divisum (PD) is the most common congenital variant of the pancreas and
      has been implicated as a cause of pancreatitis; however, endoscopic treatment is
      controversial. Our objective was to examine patient response to endotherapy for
      treatment of symptomatic PD in adult patients in a systematic review of the
      literature. A systematic review of all case series and case-control studies with
      ten or more patients undergoing endotherapy for treatment of symptomatic PD
      indicated by acute recurrent pancreatitis (ARP), chronic pancreatitis (CP), or
      chronic abdominal pain (CAP) was performed. PubMed, Embase, and Web of Science
      databases were searched from inception through February 2013 using [pancreas
      divisum] AND [endoscopic retrograde cholangiopancreatography (ERCP)] OR
      [endotherapy] OR [endoscopy] as search terms. Importantly, the majority of
      studies were retrospective in nature, significantly limiting analysis capacity.
      Main outcomes measures included endotherapy response rate in patients with PD and
      ARP, CP, or CAP. Twenty-two studies were included in the review, with a total of
      838 patients. Response to endoscopy was seen in 528 patients, but response rate
      varied by clinical presentation. Patients with ARP had a response rate ranging
      from 43% to 100% (median 76%). Reported response rates were lower in the other
      two groups, ranging from 21% to 80% (median 42%) for patients with CP and 11%-55%
      (median 33%) for patients with CAP. Complications reported included perforation,
      post-endoscopic retrograde cholangiopancreatography pancreatitis, bleeding, and
      clogged stents. Endotherapy appears to offer an effective treatment option for
      patients with symptomatic PD, with the best results in patients presenting with
      ARP.

PMID- 25062872
TI  - Diagnosing acute pancreatitis in children: what is the diagnostic yield and
      concordance for serum pancreatic enzymes and imaging within 96 h of presentation?
AB  - BACKGROUND/OBJECTIVES: There are limitations and challenges with the diagnosis of
      acute pancreatitis (AP) in children. We evaluated the diagnostic yield and
      concordance for serum pancreatic enzymes and imaging in children with AP.
      METHODS: A retrospective review of laboratory and radiographic results within 96
      h of AP presentation (January 2000-July 2011) was performed at two paediatric
      hospitals. Observed agreement and kappa statistics (kappa) were determined
      between outcomes of bloods (lipase and/or amylase) and imaging (ultrasound (US)
      and/or computed tomography (CT)). RESULTS: A total of 103/131 (79%) AP cases had
      both bloods and imaging performed (within 96 h). Overall, lipase, amylase, US and
      CT were consistent with an AP diagnosis in 93% (93/100), 54% (43/80), 27% (21/77)
      and 67% (28/42) of cases respectively. The diagnostic yield for combinations of
      blood(s) and imaging(s) tests was higher than any single test and blood tests
      alone. The observed agreement between bloods 'lipase or amylase' and imaging 'US
      or CT,' was 40%. The kappa was -0.083 suggesting no agreement. In 55% of cases,
      enzymes were positive whilst imaging was negative and the converse was evident in
      5% of cases. There was no agreement between the various diagnostic tests, except
      between amylase and US, which had fair agreement. CONCLUSION: Elevations in serum
      lipase contributed to the diagnosis more often than other tests. Combinations of
      blood(s) and imaging(s) tests have an increased diagnostic yield. Serum enzyme
      elevation and imaging changes poorly correlated. At least 5% of cases of AP may
      be missed if imaging is not performed.

PMID- 25062873
TI  - Clinical utility of the revised Atlanta classification of acute pancreatitis in a
      prospective cohort: have all loose ends been tied?
AB  - BACKGROUND AND AIM: Revision of the Atlanta classification for acute pancreatitis
      (AP) was long awaited. The Revised Atlanta Classification has been recently
      proposed. In this study, we aim to prospectively evaluate and validate the
      clinical utility of the new definitions. PATIENT AND METHODS: 163 consecutive
      patients with AP were followed till death/6 mths after discharge. AP was
      categorized as mild (MAP) (no local complication[LC] and organ failure[OF]),
      moderate (MSAP)(transient OF and/or local/systemic complication but no persistent
      OF) and severe (SAP) AP (persistent OF). LC included acute peripancreatic fluid
      collections, pseudocyst, acute necrotic collection, walled-off necrosis, gastric
      outlet dysfunction, splenic/portal vein thrombosis, and colonic necrosis.
      Baseline characteristics (age/gender/hematocrit/BUN/SIRS/BISAP) and outcomes
      (total hospital stay/need for ICU care/ICU days/primary infected (peri)pancreatic
      necrosis[IN]/in-hospital death) were compared. RESULTS: 43 (26.4%) patients had
      ANP, 87 (53.4%) patients had MAP, 58 (35.6%) MSAP and 18 (11.04%) SAP. Among the
      baseline characteristics, BISAP score was significantly higher in MSAP compared
      to MAP [1.6 (1.5-2.01) vs 1.2 (1.9-2.4); p = 0.002]; and BUN was significantly
      higher in SAP compared to MSAP[64.9 (50.7-79.1) vs 24.9 (20.7-29.1); p < 0.0001].
      All outcomes except mortality were significantly higher in MSAP compared to MAP.
      Need for ICU care (83.3%vs43.1%; p = 0.01), total ICU days[7.9 (4.8-10.9) vs 3.5
      (2.7-5.1); p = 0.04] and mortality (38.9%vs1.7%; p = 0.0002) was significantly
      more in SAP compared to MSAP. 8/18 (44.4%) patients had POF within seven days of
      disease onset (early OF). This was associated with 37.5% of total in-hospital
      mortality. Patients with MSAP who had primary IN (n = 10) had similar outcomes as
      SAP. CONCLUSIONS: This study prospectively validates the clinical utility of the
      Revised Atlanta definitions of AP. However, MSAP patients with primary infected
      necrosis may behave as SAP. Furthermore, patients with early severe acute
      pancreatitis (early OF) could represent a subgroup that needs to be dealt with
      separately in classification systems.

PMID- 25062874
TI  - Comparison between ulinastatin and nafamostat for prevention of post-endoscopic
      retrograde cholangiopancreatography complications: a prospective, randomized
      trial.
AB  - OBJECTIVES: Pancreatitis is the most common complication of endoscopic retrograde
      cholangiopancreatography (ERCP). The aim of this prospective trial was to compare
      the effect of ulinastatin and nafamostat on the prophylaxis of post-ERCP
      complications. METHODS: A total of 159 patients who underwent ERCP were divided
      into ulinastatin (n = 53), nafamostat (n = 53) and control (n = 53) groups. Each
      patient received ulinastatin (150,000 units), nafamostat (20 mg), or placebo from
      2-4 h before ERCP to 6-8 h after ERCP. The primary endpoint was the incidence of
      PEP, and the secondary endpoints were the incidence of post-ERCP hyperamylasemia,
      hyperlipasemia and abdominal pain. RESULTS: The overall incidence of PEP was 6.3%
      (10/159) and no significant differences were observed between ulinastatin and
      nafamostat groups in terms of the incidences of PEP (1.9% and 3.8%, P = 0.560),
      hyperamylasemia, hyperlipasemia, and abdominal pain, although these were
      significantly lower than those of the control group (P < 0.001). CONCLUSIONS:
      There was no significant difference for preventing PEP between ulinastatin and
      nafamostat and both drugs were efficacious for preventing post-ERCP
      complications.

PMID- 25062875
TI  - Pancreas volume measurement in patients with Type 2 diabetes using magnetic
      resonance imaging-based planimetry.
AB  - BACKGROUND/OBJECTIVES: To compare pancreas volume (PV) measurement using MRI
      based planimetry in patients with Type 2 diabetes mellitus (DM) to PV in
      normoglycemic individuals. METHODS: Our institutional review board granted
      approval of this retrospective study with waiver of informed consent. We searched
      2296 consecutive abdominal MRI studies performed at our hospital on patients with
      no pancreas pathology between September 1, 2010 and February 28, 2013, for those
      who also had a fasting plasma glucose and/or hemoglobin A1C within six months of
      the MRI examination. For those patients who met biochemical criteria for DM, we
      used medication and clinical records to confirm that 32 of these patients had
      Type 2 DM. The pancreas contours of 32 Type 2 diabetics and 50 normoglycemic
      individuals were then traced on non-gadolinium T1-weighted 3D fat suppressed
      gradient echo images by a radiologist trained in abdominal MRI to calculate PV.
      PV index (PVI) was calculated as PV/weight to adjust PV for each patient's
      weight. PVs and PVIs in both cohorts were compared using t-tests and regression
      models correcting for weight, age and gender. RESULTS: Patients with Type 2 DM
      had significantly lower PVs than normoglycemic individuals (72.7 +/- 20.7 cm(3)
      versus 89.6 +/- 22.7 cm(3), p < 0.001), and significantly lower PVIs (1.0 +/- 0.3
      cm(3)/kg versus 1.3 +/- 0.3 cm(3)/kg, p < 0.001). Using regression models, we
      found that given the same age, weight and gender, the PV in a patient with Type 2
      DM was 17.9 mL (20%) lower compared to a normoglycemic individual (p < 0.001).
      CONCLUSION: PV is reduced in Type 2 DM compared to normoglycemic individuals and
      can be measured using MRI without contrast injection.

PMID- 25062876
TI  - The nutritional status and factors contributing to malnutrition in children with
      chronic pancreatitis.
AB  - BACKGROUND/OBJECTIVES: The present study was undertaken to determine the
      prevalence of malnutrition among children with chronic pancreatitis (CP).
      Furthermore, we aimed to evaluate the relationship between etiological factors of
      CP, its clinical characteristics, and the severity of malnutrition. METHODS: The
      study included 208 children with CP (113 girls and 95 boys; mean age: 10.8 years,
      range: 1.6-18 years), hospitalized at our center between 1988 and 2012. The
      severity of malnutrition was graded on the basis of Cole's ratios, and its
      prevalence was analyzed according to the etiological factors of pancreatitis.
      Moreover, the analysis of discrimination was performed to identify the factors
      contributing to malnutrition among the following variables: age at CP onset,
      duration of CP, number of CP exacerbations, the number of ERCPs performed, the
      grade of pancreatic damage documented on imaging, co-occurrence of diabetes, and
      the results of 72-h fecal fat quantification. RESULTS: We documented features of
      malnutrition in 52 (25%) children with CP, including 36 (17.3%) patients with
      moderate malnutrition, and 2 (0.96%) with severe malnutrition. There was no
      significant difference in the prevalence of malnutrition between groups of
      patients with various etiological factors of chronic pancreatitis. The age at CP
      onset showed the best discrimination ability of malnourished patients: the mean
      age at disease onset in a subgroup of malnourished children was significantly
      higher than in children with Cole's index >85%. CONCLUSIONS: A considerable
      percentage of children with CP can suffer from clinically significant
      malnutrition. Later age at CP onset predisposes to development of malnutrition.

PMID- 25062877
TI  - Small intestinal bacterial overgrowth is common both among patients with
      alcoholic and idiopathic chronic pancreatitis.
AB  - BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is known to occur in
      patients with chronic pancreatitis, particularly of alcoholic etiology. There
      are, however, scanty data on frequency of SIBO in patients with chronic
      idiopathic pancreatitis and factors associated with its occurrence. METHODS: 68
      patients with chronic pancreatitis and 74 age and gender-matched healthy subjects
      (HS) were evaluated for SIBO using glucose hydrogen breath test (GHBT).
      Persistent rise in breath hydrogen 12 ppm above basal (at least two recordings)
      was diagnostic of SIBO. RESULT: SIBO was diagnosed more often among patients with
      chronic pancreatitis than controls (10/68 [14.7%] vs. 1/74 controls [1.3%]; p =
      0.003). Of 68 patients, 22 (32.3%) had alcoholic and 46 (67.6%) had idiopathic
      chronic pancreatitis. SIBO was as commonly detected among patients with alcoholic
      as idiopathic pancreatitis (3/22 [13.6%] vs. 7/46 [15.2%]; p = 0.86). Age,
      gender, body mass index (BMI), steatorrhoea, pain, analgesic use, pancreatic
      calcifications and use of pancreatic enzyme supplements had no relationship with
      the presence of SIBO. Diabetes mellitus tended to be commoner among patients with
      chronic pancreatitis with than without SIBO (6/10 [60%] vs. 18/58 [31%]; p =
      0.07). CONCLUSION: SIBO was commoner among patients with chronic pancreatitis,
      both alcoholic and idiopathic, than HS. Though presence of SIBO among patients
      with chronic pancreatitis tended to be commoner among those with diabetes
      mellitus, there was no relationship with age, gender, BMI, steatorrhoea, pain,
      analgesic use, pancreatic calcifications and use of pancreatic enzyme
      supplements.

PMID- 25062878
TI  - Does tobacco influence the natural history of autoimmune pancreatitis?
AB  - Tobacco recently appeared as a major independent factor adversely influencing the
      natural course of alcoholic chronic pancreatitis. However, the role of tobacco in
      patients with autoimmune pancreatitis (AIP) has never been studied. Type 2 AIP is
      associated with inflammatory bowel disease, especially ulcerative colitis in
      which smoking is protective. The aim of our study was to evaluate the influence
      of smoking on course of AIP. PATIENTS AND METHODS: All consecutive patients
      followed in our centre for AIP according to ICDC were studied. Tobacco
      consumption was recorded. A relation between smoking and all event related to AIP
      was searched for. RESULTS: 96 patients with type 1 (73%) or type 2 (27%) AIP were
      included; 76% of patients were low smokers (never, ex- or smokers <10 p.y.) and
      24% were high smokers (>=10 p.y.). The mean follow-up was 60 months [5-188]. AIP
      relapse was observed in 26% of patients. At the end-point, smokers >=10 p.y.
      presented more frequently diabetes (50% vs 27%, p = 0.04) and imaging pancreatic
      damages (59% vs 34%, p = 0.02) than low smokers. There was also a non significant
      tendency to observe more frequently exocrine insufficiency and relapse in smokers
      >=10 pack-year. No protective effect of smoking was observed in the subgroup of
      patients with type 2 AIP and ulcerative colitis. CONCLUSIONS: In patients with
      AIP, high tobacco intake is associated with the risk of imaging pancreatic
      damages and with the occurrence of diabetes. Smoking cessation should be
      recommended.

PMID- 25062879
TI  - Prognostic assessment of different lymph node staging methods for pancreatic
      cancer with R0 resection: pN staging, lymph node ratio, log odds of positive
      lymph nodes.
AB  - BACKGROUND AND AIMS: Survival after surgical resection of pancreatic
      adenocarcinoma is poor. Several prognostic factors such as the status of the
      resection margin, lymph node status, or tumour grading have been identified. The
      aims of the present study were to evaluate and compare the prognostic assessment
      of different lymph nodes staging methods: standard lymph node (pN) staging,
      metastatic lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS)
      in pancreatic cancer after pancreatic resection. MATERIALS AND METHODS: Data were
      retrospectively collected from 143 patients who had undergone R0 pancreatic
      resection for pancreatic ductal adenocarcinoma. Survival curves (Kaplan-Meier and
      Cox proportional hazard models), accuracy, and homogeneity of the 3 methods (LNR,
      LODDS, and pN) were compared to evaluate the prognostic effects. RESULTS:
      Multivariate analysis demonstrated that LODDS and LNR were an independent
      prognostic factors, but not pN classification. The scatter plots of the
      relationship between LODDS and the LNR suggested that the LODDS stage had power
      to divide patients with the same ratio of node metastasis into different groups.
      For patients in each of the pN or LNR classifications, significant differences in
      survival could be observed among patients in different LODDS stages. CONCLUSION:
      LODDS and LNR are more powerful predictors of survival than the lymph node status
      in patients undergoing pancreatic resection for ductal adenocarcinoma. LODDS
      allows better prognostic stratification comparing LNR in node negative patients.

PMID- 25062880
TI  - Abnormal distribution of peripheral lymphocyte subsets induced by PDAC modulates
      overall survival.
AB  - BACKGROUND/OBJECTIVES: The impairment of the immune system is prevalent in
      patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC).
      The present study aimed to evaluate alternations of peripheral lymphocyte subsets
      in patients with PDAC, and also to assess the prognostic value of observed
      changes. METHODS: We recruited 160 consecutive PDAC patients who had undergone
      radical surgical resection between 2010 and 2013. To investigate the prognostic
      factors, we detected the peripheral lymphocyte subsets in PDAC by flow cytometry,
      including T cells (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD8(+)CD28(+)), regulatory
      T cells (Tregs, CD4(+)CD25(+)CD127(-)), natural killer cells (NK cells, CD3(
      )CD56(+)) and B cells (CD19(+)). We also evaluated the clinical and pathological
      features of these patients. Survival analysis was performed by univariate and
      multivariate analyses. RESULTS: Our results indicated the profile of peripheral
      lymphocyte subsets undergone profound changes in PDAC patients. Univariate and
      multivariate analysis indicated the levels of peripheral lymphocyte subsets
      (CD19(+) B cells, Tregs and CD8(+)CD28(+) T cells) were independent predictors
      for overall survival. The results also suggested that the systemic impairment of
      immune system in patients with PDAC, was reversed when primary tumor was removed.
      CONCLUSIONS: The present study provided some evidences that the impairment of
      host immunity induced by PDAC may play a role in the survival of patients.

PMID- 25062881
TI  - Evidence-based value of prophylactic intraperitoneal drainage following
      pancreatic resection: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Prophylactic intraperitoneal drainage is usually
      indwelled after abdominal operation. This study assessed whether prophylactic
      intraperitoneal drainage was of value after pancreatic resection. METHODS: A
      systematic literature search was performed to identify relevant articles. Data
      aggregation and analysis were performed using RevMan 5.0 software package.
      RESULTS: A randomized controlled trial and seven observational cohort studies
      including a total of 2690 patients were eligible. The overall and major
      complication rates and the occurrence of pancreatic fistula in patients with
      drainage were higher than those without drainage. Prophylactic intraperitoneal
      drainage was not associated with a statistically significant reduction in the
      need for percutaneous drainage, reoperation and readmission, or with an increase
      in mortality. CONCLUSION: The present meta-analysis demonstrated that
      prophylactic intraperitoneal drainage after pancreatic resection appears to be
      unable to improve the postoperative course, and may be associated with more
      severe and higher rate of complication and increased pancreatic fistula
      occurrence. There is a serious bias in the criteria to insert drain or not in
      these retrospective studies. Therefore these results should be confirmed by
      randomized controlled trial.

PMID- 25062882
TI  - Insulinoma clinically misdiagnosed as vertebrobasilar insufficiency in an obese
      patient with recurrent episodes of loss of consciousness.

PMID- 25062883
TI  - Childhood cystic teratoma of the pancreas: clinical presentation, evaluation and
      management.
AB  - Pancreatic cystic teratoma in children is extremely rare. Here we present a
      female infant with a mature cystic teratoma of the pancreatic body. The patient
      was admitted for a palpable abdominal mass and anorexia. Computed tomography (CT)
      indicated a huge cystic mass in the abdominal cavity. Exploratory laparotomy was
      performed, and the tumor was excised completely. Pathology confirmed the tumor
      was a mature cystic teratoma of pancreatic origin. Two months after the initial
      surgery, a pseudocyst was detected and then cystojejunostomy was performed.
      Fourteen months after the second surgery, tumor relapse occurred and distal
      pancreatectomy was performed. The patient remained well without tumor recurrence
      during the next 24 months of follow-up. Our experience suggests that clinical
      manifestations of children with pancreatic cystic teratomas might be nonspecific
      and preoperative diagnosis is difficult. Radical tumor resection and maximized
      preservation of healthy pancreatic tissue should always be balanced in surgical
      treatment.

PMID- 25062884
TI  - Autoimmune pancreatitis type-1 associated with intraduct papillary mucinous
      neoplasm: report of two cases.
AB  - Chronic pancreatitis lesions usually embrace both intraduct papillary mucinous
      neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC). Patients at
      genetically-determined high risk of PDAC often harbor IPMN and/or chronic
      pancreatitis, suggesting IPMN, chronic pancreatitis and PDAC may share
      pathogenetic mechanisms. Chronic autoimmune pancreatitis (AIP) may also herald
      PDAC. Concurrent IPMN and AIP have been reported in few patients. Here we
      describe two patients with IPMN who developed type-1 AIP fulfilling the Honolulu
      and Boston diagnostic criteria. AIP diffusively affected the whole pancreas, as
      well as peripancreatic lymph nodes and the gallbladder. Previous pancreatic
      resection of focal IPMN did not show features of AIP. One of the patients carried
      a CFTR class-I mutation. Of notice, serum IgG4 levels gradually decreased to
      normal values after IPMN excision. Common risk factors to IPMN and AIP may
      facilitate its coincidental generation.

PMID- 25062885
TI  - Size-dependent gender modification in Lilium apertum (Liliaceae): does this
      species exhibit gender diphasy?
AB  - BACKGROUND AND AIMS: Variation in the relative female and male reproductive
      success of flowering plants is widespread, despite the fundamental hermaphroditic
      condition of the majority of species. In many hermaphroditic populations,
      environmental conditions and their influence on development and size can
      influence the gender expression of individuals through the formation of
      hermaphroditic and unisexual flowers. This study investigates the hypothesis that
      the bulbous, animal-pollinated, perennial Lilium apertum (Liliaceae) exhibits a
      form of size-dependent gender modification known as gender diphasy, in which the
      sexual expression of individuals depends on their size, with plants often
      changing sex between seasons. METHODS: Variation in floral traits was examined in
      relation to their size using marked individuals in natural populations, and also
      under glasshouse conditions. Measurements were taken of the height, flower
      number, floral sex expression, flower size, flower biomass and pollen production
      of individuals over consecutive years between 2009 and 2012 in seven populations
      in south-west China. KEY RESULTS: Flowers of L. apertum are either perfect
      (hermaphroditic) or staminate (male) and, in any given season, plants exhibit one
      of three sex phenotypes: only hermaphrodite flowers, a mixture of hermaphroditic
      and male flowers, or only male flowers. Transitions between each of these sex
      phenotypes were observed over consecutive years and were commonly size-dependent,
      particularly transitions from small plants bearing only male flowers to those
      that were taller with hermaphroditic flowers. Hermaphroditic flowers were
      significantly larger, heavier and produced more pollen than male flowers.
      CONCLUSIONS: The results for L. apertum are consistent with the 'size advantage
      hypothesis' developed for animal species with sex change. The theory predicts
      that when individuals are small they should exhibit the sex for which the costs
      of reproduction are less, and this usually involves the male phase. L. apertum
      provides an example of gender diphasy, a rare sexual system in flowering plants.

PMID- 25062886
TI  - Branching patterns of root systems: quantitative analysis of the diversity among
      dicotyledonous species.
AB  - BACKGROUND AND AIMS: Root branching, and in particular acropetal branching, is a
      common and important developmental process for increasing the number of growing
      tips and defining the distribution of their meristem size. This study presents a
      new method for characterizing the results of this process in natura from scanned
      images of young, branched parts of excavated roots. The method involves the
      direct measurement or calculation of seven different traits. METHODS: Young
      plants of 45 species of dicots were sampled from fields and gardens with uniform
      soils. Roots were separated, scanned and then measured using ImageJ software to
      determine seven traits related to root diameter and interbranch distance.
      RESULTS: The traits exhibited large interspecific variations, and covariations
      reflecting trade-offs. For example, at the interspecies level, the spacing of
      lateral roots (interbranch distance along the parent root) was strongly
      correlated to the diameter of the finest roots found in the species, and showed a
      continuum between two opposite strategies: making dense and fine lateral roots,
      or thick and well-spaced laterals. CONCLUSIONS: A simple method is presented for
      classification of branching patterns in roots that allows relatively quick
      sampling and measurements to be undertaken. The feasibilty of the method is
      demonstrated for dicotyledonous species and it has the potential to be developed
      more broadly for other species and a wider range of enivironmental conditions.

PMID- 25062887
TI  - Research advances on apoptosis caused by quantum dots.
AB  - Recently, quantum dots (QDs) have been widely applied in biological and
      biomedical fields such as cell labeling, living tissue imaging, and photodynamic
      therapy because of their superior optical properties. Meanwhile, the potential
      biological negative effects and/or toxic effects of QDs have become increasingly
      important, especially the cytotoxicity caused by QDs. One of the common
      cytotoxicity when living organisms are treated with QD is apoptosis, where many
      attempts have been made to explain the mechanisms of apoptosis caused by QDs'
      use. One of the mechanisms is the production of cadmium ion (Cd(2+)) and reactive
      oxygen species (ROS). Excess generation of ROS will result in oxidative stress
      that would mediate apoptosis. Furthermore, the activation of cell death receptors
      and mitochondria-dependent such as B cell lymphoma 2 (Bcl-2) family and the
      caspase family could onset apoptosis. Signal transduction such as some classical
      signal pathways of PI3K-AKT, NF-E2-related factor 2 (Nrf2)-antioxidant response
      element (ARE), mitogen-activated protein kinases (MAPKs), and nuclear factor
      kappa B (NF-kappaB) also plays an important role in the regulation of apoptosis.
      Several ways to reduce the apoptotic rate have been introduced, such as surface
      modification, controlling, the dose, size, and exposure time of QDs as well as
      using antioxidants or inhibitors. In this review, we attempted to review the most
      recent findings associated with apoptosis caused by QDs so as to provide some
      guidelines for a safer QD application in the future. 

PMID- 25062888
TI  - Selenium downregulates oxidative stress-induced activation of leukotriene pathway
      in experimental rats with diabetic cardiac hypertrophy.
AB  - Cardiac hypertrophy has been considered as an important risk factor of morbidity
      and mortality. It is characterized as thickening of ventricle wall of the heart
      and consequent reduction in the contracting ability of the heart to pump the
      blood. Hyperglycemia-induced reactive oxygen species act as major mediators of
      diabetic complications. Inflammation plays an essential role in the development
      of diabetic cardiac hypertrophy. Selenium has been shown to induce insulin-like
      and anti-inflammatory effects in human and experimental animals. But, its
      mechanism of action has not been elucidated. Hence, in order to probe into its
      mechanism at molecular level, we designed an experiment to study the effect of
      selenium as sodium selenite in streptozotocin-induced diabetic rats. The rats
      were divided into four groups and maintained as follows: (1) controls, (2) sodium
      selenite-treated controls, (3) diabetic, and (4) sodium selenite-treated diabetic
      rats. Duration of the experiment was 30 days. Selenium supplementation enhanced
      the streptozotocin-induced reduction in the activities of antioxidant enzymes,
      decreased the serum glucose level, glycated hemoglobin content, concentration of
      high-sensitivity C-reactive protein, levels of lipid peroxidation products, as
      well as inflammatory parameters. Decrease in the phospholipase activity by
      selenium supplementation also contributed to the downregulation of leukotriene
      pathway. It also downregulated the expressions of nuclear transcription factor
      kappaB (NFkappaB), lipoxygenase, cyclooxygenase, 5-lipoxygenase-activating
      protein, and receptor for leukotriene B4. Hence, selenium decreased the
      production of reactive oxygen species and inhibited the activation of NFkappaB
      mediated transcription of pro-inflammatory mediators which resulted in the
      downregulation of leukotriene pathway in diabetic cardiac hypertrophy.

PMID- 25062889
TI  - Does excess fluoride exposure via drinking water affect the platelet indices in
      humans?

PMID- 25062890
TI  - Bioactivity-guided chemical analysis of Melia azedarach L. (Meliaceae),
      displaying antidiabetic activity.
AB  - One new Euphane-type triterpenoid 3beta-hydroxytirucalla-5, 24-dien-21-oic acid
      (1), and ten known compounds (2-11) were isolated from Melia azedarach L. through
      bioassay-guided chemical analysis. The structures of the isolated compounds were
      established by means of 1D and 2D NMR spectroscopic ((1)H, (13)C, DEPT, COSY,
      HSQC and HMBC) and MS spectral analyses. All the fractions and isolated pure
      compounds were evaluated for antidiabetic activity by determining their
      inhibitory effects on PTP-1B enzyme as well as glucose uptake stimulation in
      C2Cl2 myoblasts cells. Compounds 4 and 7 showed significant in vitro PTP-1B
      inhibitory activity with 69.2 and 66.8% inhibition at 10 MUg/ml concentrations
      respectively.

PMID- 25062891
TI  - Kirenol stimulates osteoblast differentiation through activation of the BMP and
      Wnt/beta-catenin signaling pathways in MC3T3-E1 cells.
AB  - Kirenol has been reported to possess anti-oxidant, anti-inflammatory, anti
      allergic, anti-adipogenic, and anti-arthritic activities; however, its effect on
      osteoblast differentiation has not yet been reported. The aim of the present
      study was to evaluate the effect of kirenol on osteoblast differentiation through
      activation of the bone morphogenetic protein (BMP) and Wnt/beta-catenin signaling
      pathways in MC3T3-E1 cells. Kirenol markedly promoted alkaline phosphatase (ALP)
      activity and mineralization. Kirenol not only increased the expression of
      osteoblast differentiation markers, such as ALP, type I collagen (ColA1), and
      osteopontin (OPN), but also increased the expression of osteoprotegerin/receptor
      activator of nuclear factor kappa B ligand (OPG/RANKL) ratio. The effects of
      kirenol on osteoblast differentiation were accompanied by stimulating the
      expression of the BMP and Wnt/beta-catenin signaling pathways, including BMP2,
      runt-related transcription factor 2 (Runx2), osterix (Osx), low density
      lipoprotein receptor related protein 5 (LRP5), disheveled 2 (DVL2), beta-catenin,
      cyclin D1 (CCND1), and phosphorylated glycogen synthase kinase 3beta (GSK3beta).
      In addition, kirenol up-regulated the expression of beta-catenin, CCND1, ALP, and
      ColA1 which were down-regulated by siRNA knockdown of beta-catenin. Overall,
      these results demonstrate that kirenol is capable of promoting osteoblast
      differentiation in MC3T3-E1 cells through activation of the BMP and Wnt/beta
      catenin signaling pathways, suggesting that it is a potential candidate target
      for treating or preventing osteoporosis. 

PMID- 25062892
TI  - A low computation cost method for seizure prediction.
AB  - The dynamic changes of electroencephalograph (EEG) signals in the period prior to
      epileptic seizures play a major role in the seizure prediction. This paper
      proposes a low computation seizure prediction algorithm that combines a fractal
      dimension with a machine learning algorithm. The presented seizure prediction
      algorithm extracts the Higuchi fractal dimension (HFD) of EEG signals as features
      to classify the patient's preictal or interictal state with Bayesian linear
      discriminant analysis (BLDA) as a classifier. The outputs of BLDA are smoothed by
      a Kalman filter for reducing possible sporadic and isolated false alarms and then
      the final prediction results are produced using a thresholding procedure. The
      algorithm was evaluated on the intracranial EEG recordings of 21 patients in the
      Freiburg EEG database. For seizure occurrence period of 30 min and 50 min, our
      algorithm obtained an average sensitivity of 86.95% and 89.33%, an average false
      prediction rate of 0.20/h, and an average prediction time of 24.47 min and 39.39
      min, respectively. The results confirm that the changes of HFD can serve as a
      precursor of ictal activities and be used for distinguishing between interictal
      and preictal epochs. Both HFD and BLDA classifier have a low computational
      complexity. All of these make the proposed algorithm suitable for real-time
      seizure prediction.

PMID- 25062893
TI  - Substance use disorders and psychotic disorders in epilepsy: a population-based
      registry study.
AB  - BACKGROUND: Epilepsy affects around 70 million people worldwide. Psychiatric
      comorbidity may add to the burden of the disease. We studied substance use
      disorders and psychotic disorders among people with epilepsy from a population
      based perspective. METHODS: Norwegian specialist health services (hospitals and
      outpatient clinics) report diagnoses for individual patients to the Norwegian
      Patient Register. We used information on subjects born in 1930-1994 who were
      registered with a diagnosis of epilepsy at least once during the five-year period
      of 2008-2012. We compared the proportion of people with epilepsy registered with
      substance use disorders (alcohol use disorders or non-alcohol drug use disorders)
      and psychotic disorders (schizophrenia spectrum disorders or bipolar disorder)
      with similar figures in the population without epilepsy. We applied chi-square
      tests and log-binomial regression for analysis. RESULTS: Overall, 0.90% of the
      Norwegian adult population was registered with epilepsy in somatic hospitals
      during 2008-2012. The total proportion registered with alcohol use disorder was
      5.74% among people with epilepsy and 1.29% in the population without epilepsy
      (age- and sex-adjusted relative risk [RR]: 4.42, 95% confidence interval [CI]:
      4.22-4.62). The corresponding figures were 4.32% and 1.22% (RR 3.86 [95% CI: 3.67
      4.06] for drug use disorder, 1.72% and 0.60% (RR 2.94 [95% CI: 2.71-3.19]) for
      schizophrenia spectrum disorders, and 1.50% and 0.68% (RR 2.29 [95% CI: 2.10
      2.49]) for bipolar disorder. CONCLUSION: People with epilepsy were more often
      registered with substance use disorders and psychotic disorders than people
      without epilepsy. Psychiatric comorbidity requires particular attention in both
      diagnostic work-up and management of epilepsy, and creates complex medical
      challenges that require close cooperation between neurologists and psychiatrists.
      These findings may have implications for the organization and further development
      of comprehensive epilepsy care.

PMID- 25062894
TI  - Giant prolactinomas: clinical manifestations and outcomes of 16 Arab cases.
AB  - BACKGROUND: The management of giant prolactinomas remains a major challenge,
      despite dopamine agonists being the first line of treatment, owing to its
      efficacy to normalize prolactin levels and reduce tumor volume. The aim of this
      study is to characterize the therapeutic aspects, manifestations and outcomes of
      16 cases of giant prolactinomas admitted at a single tertiary center in Riyadh,
      Saudi Arabia. METHODS: Retrospective data collection involving 16 Saudi patients
      diagnosed with giant prolactinoma at the Pituitary Clinic in King Fahad Medical
      City, Riyadh, Saudi Arabia between January 2006 and July 2012. RESULTS: A total
      of 16 patients (ten males; six females) with age of diagnosis between 21 and 55
      years (mean 34.9 years) were included in the analysis. The most common presenting
      features include headache, visual defects and sexual dysfunction. Baseline mean
      serum prolactin level were extremely high for both sexes which eventually
      decreased by as much as 97% after cabergoline treatment. Serum prolactin
      concentrations completely normalized in six patients and significantly decreased
      in five patients 3-5 times that of normal range. Tumor volume also decreased by
      an average of 86% for males and 87% for females. Two patients had no tumor size
      change with cabergoline and required surgery. CONCLUSION: Findings indicate that
      cabergoline provides dramatic clinical improvements with excellent safety
      profile. Cabergoline should therefore be considered as the primary therapy for
      giant prolactinomas.

PMID- 25062895
TI  - Polymorphism of glyceryl behenates: from the individual compounds to the
      pharmaceutical excipient.
AB  - The present paper deals with the crystallization behavior of glyceryl behenate
      mixtures that are extensively used in the field of drug delivery. The aim of the
      study was to understand the structural and thermal behaviors of Compritol((r)) by
      considering first the individual polymorphism of the main components constituting
      this excipient and then their mixtures. This excipient mainly contains dibehenin
      (~50%), tribehenin (~30%) and monobehenin (20%). It appeared clearly that the
      mixture polymorphism did not result from a simple addition of the individual
      behavior. Indeed, the solid state organization of this excipient strongly
      depended on the presence of the third main component, monobehenin, into the
      mixture. Furthermore, a threshold ratio of monobehenin, at least 10%, must be
      reach in order to obtain the typical structural organization (co-existence of
      alpha/sub-alpha subcells) and thermal behavior (solid-solid transition and
      melting) of Compritol((r)). This underlines that special attention is required
      when mixing Compritol((r)) with other pharmaceutical ingredients that could trap
      monoglycerides and modify the equilibrium present in the pure excipient. 

PMID- 25062896
TI  - Geometry of membrane fission.
AB  - Cellular membranes define the functional geometry of intracellular space.
      Formation of new membrane compartments and maintenance of complex organelles
      require division and disconnection of cellular membranes, a process termed
      membrane fission. Peripheral membrane proteins generally control membrane
      remodeling during fission. Local membrane stresses, reflecting molecular geometry
      of membrane-interacting parts of these proteins, sum up to produce the key
      membrane geometries of fission: the saddle-shaped neck and hour-glass hemifission
      intermediate. Here, we review the fundamental principles behind the translation
      of molecular geometry into membrane shape and topology during fission. We
      emphasize the central role the membrane insertion of specialized protein domains
      plays in orchestrating fission in vitro and in cells. We further compare
      individual to synergistic action of the membrane insertion during fission
      mediated by individual protein species, proteins complexes or membrane domains.
      Finally, we describe how local geometry of fission intermediates defines the
      functional design of the protein complexes catalyzing fission of cellular
      membranes. 

PMID- 25062897
TI  - Immunization of lambs with the S48 strain of Toxoplasma gondii reduces tissue
      cyst burden following oral challenge with a complete strain of the parasite.
AB  - This study evaluates the influence of immunizing lambs with the incomplete S48
      strain of Toxoplasma gondii, on parasite dissemination following a live oral
      challenge with a complete strain of T. gondii (M4). Lambs were culled at 14, 28
      and 42 days post challenge. Parasite DNA was detected at significantly (p<0.0001)
      lower levels in samples from the vaccinated/challenged group (0% in heart and
      5.9% in skeletal muscles), when compared to the non-vaccinated/challenged animals
      (75% heart, 87.9% skeletal muscle). S48 T. gondii DNA was found in muscle or
      lymph nodes until 42 days post infection, suggesting that parasite DNA or
      tachyzoites could persist longer after immunization than previously thought. Non
      vaccinated/challenged animals showed more frequent lesions in muscles and central
      nervous system than the vaccinated animals. These results demonstrate that
      vaccination of lambs with the incomplete S48 T. gondii strain, can protect
      against establishment of tissue cysts following challenge with a complete strain
      of T. gondii. Consumption of undercooked meat containing T. gondii cysts is a
      major route of transmission to people, therefore vaccination of food animals may
      improve the safety of meat for human consumption. 

PMID- 25062898
TI  - Is the LINX reflux management system an effective treatment for gastro
      oesophageal reflux disease?
AB  - A best evidence topic in surgery was written according to a structured protocol.
      The question addressed whether LINXTM Reflux management system is an efficacious
      treatment for patients with symptoms of gastro-oesophageal reflux disease (GORD)
      not controlled by proton pump inhibitors (PPI). Forty-eight LINX-related papers
      were identified using the reported search, of which three represented the best
      evidence to answer the clinical question. The authors, journal, date and country
      of publication, patient group, study type, relevant outcomes and results of these
      papers are tabulated. All three studies were prospective case studies. They
      demonstrated that LINX is an efficacious treatment for GORD patients with good
      short and medium term outcomes and an acceptable safety profile. Further studies
      are required to determine its long term outcomes and its relative efficacy as
      compared to other established treatments. 

PMID- 25062899
TI  - Influence of tramadol on ischemia-reperfusion injury of rats' skeletal muscle.
AB  - INTRODUCTION: Tramadol has been shown to decrease ischemia-reperfusion injuries
      in myocardial or brain tissues. The aim of this study was to assess the effects
      of tramadol on ischemia-reperfusion injury in a rat hind limb ischemia
      reperfusion model. METHODS: Forty-five healthy adult male Wistar rats were
      randomized into three experimental groups as follows: Sham, Ischemia-reperfusion
      and Ischemia-reperfusion + tramadol groups. Ischemia was induced in anesthetized
      rats by left femoral artery clipping for 2 h followed by 24 h of reperfusion.
      Tramadol (20 mg/kg) was administered intravenously immediately prior to
      reperfusion. Blood pH, pO2, pCO2, HCO3, creatine phosphokinase (CPK), lactate
      dehydrogenase (LDH) as well as plasma malondialdehyde (MDA) were measured at the
      end of the reperfusion. Left gastrocnemius muscle samples were taken for
      histological and biochemical examination. RESULTS: The pH and pCO2 were similar
      in all study groups, with no statistical significance. pO2 and HCO3 levels
      presented the highest elevation in sham and Ischemia-reperfusion + tramadol
      groups, as compared to Ischemia-reperfusion group (P < 0.05). The extent of
      muscle changes in the ischemia-reperfusion + tramadol group was significantly
      lower than ischemia-reperfusion group (P < 0.05). In comparison with other
      groups, serum and tissue MDA levels in ischemia-reperfusion group were
      significantly increased (P < 0.05). The muscle tissue glutathione (GSH),
      superoxide dismutases (SOD) and catalase (CAT) levels in the Ischemia-reperfusion
      group were significantly lower than the other groups (P < 0.05). Wet/dried weight
      ratio in ischemia-reperfusion group was significantly higher (P < 0.05) than
      subjects in other groups. CONCLUSIONS: From the histological, histochemical and
      serum biochemical perspective, the treatment with tramadol has alleviated the
      metabolic injuries in the skeletal muscle ischemia and reperfusion in this
      experimental model.

PMID- 25062900
TI  - Physical exercise improves peripheral BDNF levels and cognitive functions in mild
      cognitive impairment elderly with different bdnf Val66Met genotypes.
AB  - The benefits of physical exercise on improvements in brain-derived neurotrophic
      factor (BDNF) levels and cognitive functioning have been reported in the
      literature. However, the variability of individual responses may be linked to
      genetic differences. BDNF is considered one of the most plausible factors
      involved in the cognitive benefits associated with physical activity practice. A
      single nucleotide polymorphism localized in the gene that codes BDNF results in a
      missense mutation that promotes an amino acid substitution (Val66Met) in the
      protein. This process has been associated with decreased levels of BDNF
      secretion, with corresponding impairments in specific cognitive functions.
      Therefore, the objective of this study was to analyze the effects of a multimodal
      physical exercise program on peripheral BDNF levels and cognitive functions in
      elderly individuals with mild cognitive impairment (MCI). The participants were
      genotyped for the BDNF Val66Met polymorphism. Cognitive functions were assessed
      by the Montreal Cognitive Assessment (MoCA) prior to and after the intervention.
      Forty-five participants were assigned to the control and trained groups. The
      trained group participated in a multimodal physical training for a 16-week
      period. The results showed a significant between-subjects interaction (p < 0.05),
      which indicates the beneficial contribution of training on cognitive functions
      independent of the BDNF genotype. However, only participants with BDNF-Met
      genotypes exhibited significant improvements in peripheral BDNF levels. The BDNF
      genotype appears to modulate the effects of physical exercise on BDNF secretion,
      but it does not influence cognition. This is the first study that evaluated the
      influence of a BDNF polymorphism on physical activity and cognition performance
      in elderly MCI individuals. 

PMID- 25062901
TI  - Dietary patterns and cognitive dysfunction in a 12-year follow-up study of 70
      year old men.
AB  - BACKGROUND: Adherence to dietary patterns has been associated with cognitive
      decline and dementia, but studies are inconsistent. OBJECTIVE: Dietary patterns,
      i.e., WHO recommendations (Healthy Diet Indicator), a Mediterranean-like diet
      (modified Mediterranean Diet Score, mMDS), and a low carbohydrate high protein
      diet (LCHP), were related to incident cognitive dysfunction, as indicated by
      Alzheimer's disease (AD), all-type dementia, and all-type cognitive impairment,
      in a cohort of 1,138 elderly Swedish men. METHODS: Dietary patterns were derived
      from 7-day records. Risk relations were calculated by Cox and logistic regression
      analyses, adjusted for potential confounders. Sensitivity analysis was performed
      in a subpopulation (n = 564) with energy intake according to the Goldberg cut
      off. RESULTS: During a mean follow-up of 12 years, 84, 143, and 198 men developed
      AD, all-type dementia, and all-type cognitive impairment, respectively. There was
      no association between Healthy Diet Indicator and any of the outcomes. Hazard
      ratios associated with 1 standard deviation (SD) increment in the LCHP score were
      1.16 (95% confidence interval [CI]: 0.95, 1.43) for AD and 1.16 (95% CI: 0.99,
      1.37) for all-type dementia. mMDS was not associated with dementia diagnosis.
      Odds ratio (OR)/1 SD increase for mMDS and all-type cognitive impairment was 0.82
      (95% CI: 0.65, 1.05). In the subpopulation OR for mMDS and all-type cognitive
      impairment was 0.32 (95% CI: 0.11, 0.89). CONCLUSION: We found no strong
      associations with development of cognitive dysfunction for any of the dietary
      patterns investigated. However, there was a potentially beneficial association
      for a Mediterranean-like diet on the development of cognitive dysfunction in the
      subpopulation.

PMID- 25062902
TI  - Phase II drugs under investigation for allergic conjunctivitis.
AB  - INTRODUCTION: Ocular allergies comprise a spectrum of conditions that are
      underreported and underdiagnosed, and are frequently associated with
      rhinoconjunctivitis. Although allergic conjunctivitis is often not a sight
      threatening condition, it could have a significant impact on a person's quality
      of life, morbidity and productivity. A variety of agents are available for the
      treatment of allergic conjunctivitis, including antihistamines, mast-cell
      stabilizers, dual action agents, glucocorticoids, calcineurin inhibitors and
      immunotherapy. AREAS COVERED: The goal of this review is to investigate new
      therapeutic strategies for the treatment of ocular allergy. Within, the authors
      analyze the pharmacological management of allergic conjunctivitis and highlight
      Phase II clinical trial studies. EXPERT OPINION: Recent findings about the
      pathophysiology of allergic conjunctivitis have enabled us to gain a better
      understanding of the molecular and cellular mechanisms of ocular disease. This,
      in turn, has led to the identification of novel targets, which, in turn, has led
      to the development of new therapeutic agents that are currently under evaluation
      in the first phases of clinical development. The most interesting agents, under
      development, are the new topical glucocorticoids, leukotriene receptor
      antagonists, resolvins, interleukin-1 receptor antagonists and integrin
      antagonists. The authors now await promising results, which can confirm the
      therapeutic value of these novel emerging drugs for treating allergic
      conjunctivitis.

PMID- 25062903
TI  - A hybrid mathematical model for self-organizing cell migration in the zebrafish
      lateral line.
AB  - In this paper we propose a discrete in continuous mathematical model for the
      morphogenesis of the posterior lateral line system in zebrafish. Our model
      follows closely the results obtained in recent biological experiments. We rely on
      a hybrid description: discrete for the cellular level and continuous for the
      molecular level. We prove the existence of steady solutions consistent with the
      formation of particular biological structure, the neuromasts. Dynamical numerical
      simulations are performed to show the behavior of the model and its qualitative
      and quantitative accuracy to describe the evolution of the cell aggregate. 

PMID- 25062904
TI  - Sineoculis homeobox homolog 1 protein is associated with breast cancer
      progression and survival outcome.
AB  - Sineoculis homeobox homolog 1 (SIX1) is one of the transcription factors that act
      as master regulators of development and is frequently dysregulated in cancer.
      This study explores the roles of SIX1 in tumor progression and as a prognostic
      determinant of breast cancer. Breast cancer specimens from 262 patients were
      selected for analysis of SIX1 protein by immunohistochemistry (IHC). The
      localization of SIX1 protein was detected in MDA-MB468 breast cancer cells using
      immunofluorescence (IF) staining. The survival rates were calculated by the
      Kaplan-Meier method, and the relationship between prognostic factors and patient
      survival was also analyzed by the Cox proportional hazard models. SIX1 protein
      mainly showed cytoplasmic/perinuclear staining pattern in breast cancer using IHC
      in paraffin embedded breast cancer tissues and IF in MDA-MB468 cancer cells. The
      strongly positive rate of SIX1 protein was 61.8% (162/262) in breast cancer and
      23.1% (12/52) in ductal carcinoma in situ (DCIS), which was significantly higher
      than adjacent normal breast tissues (6.7%, 3/45). SIX1 overexpression was
      positively correlated with clinical stage, lymph node metastasis, Her2 expression
      status, and disease-free survival (DFS) and 5-year overall survival (OS) rates of
      patients with breast cancer. Moreover, patients with late stage breast cancer and
      high SIX1 expression had poorer survival rates than those with low SIX1
      expression. Further analysis using a Cox proportional hazard regression model
      revealed that high SIX1 expression emerged as a significant independent hazard
      factor for the DFS and OS rates of patients with breast cancers along with Her2
      status and clinical stage. SIX1 may potentially be used as an independent
      biomarker for prognostic evaluation of breast cancer. 

PMID- 25062905
TI  - Factors influencing occupational engagement in day centers for people with
      psychiatric disabilities.
AB  - Occupational engagement is a vital factor in people's lives since it has been
      shown to be important for health and well-being. Community-based day centers
      (DCs), both meeting place-oriented and work-oriented ones, are common service
      alternatives in many western countries for enabling engagement in productive and
      leisure occupations among people with psychiatric disabilities. Little is,
      however, known about factors influencing occupational engagement in such
      settings. We aimed to investigate how factors pertaining to day center
      attendance, socio-demographics, motivation, clinical and self-related
      characteristics were related to how day center attendees rated their occupational
      engagement in productive occupations. These variables were assessed among day
      center attendees in meeting place-oriented (n = 39) and work-oriented (n = 54)
      DCs in Sweden through questionnaires and interviews. Logistic regression models
      showed that (1) less general psychopathology and more time spent on day center
      occupations were indicators of belonging to the group with a high level of
      occupational engagement according to a median cut; (2) higher perceived self
      mastery was the only important factor with respect to ratings of occupational
      engagement above the third quartile. The models may be seen as creating a
      stepwise indication on which factors are important for reaching a medium level of
      occupational engagement (less severe general psychopathology and time spent at
      the day center) and for reaching a still higher level (a high level self
      mastery), respectively, of occupational engagement. The findings may also be
      discussed in relation to different levels of engagement in a recovery process. 

PMID- 25062907
TI  - Intraoperative fat placement in surgically refractory parasellar neoplasms to
      facilitate stereotactic radiosurgery.
AB  - BACKGROUND: In this article, we report on the technique of placing fat in between
      a sellar or parasellar neoplasm and the optic chiasm to possibly protect the
      optic chiasm from sequelae of radiation. METHODS: A review was performed on three
      patients, each of whom had planned subtotal resection with fat placed near their
      optic chiasm to facilitate future radiosurgery. RESULTS: Follow-up on our three
      patients varied from 6 months to 3 years post-stereotactic radiosurgery. The fat
      remained stable and in place. The tumors either remained stable or reduced in
      size. No infections, postoperative marker dependent neurological complications or
      unusual symptoms were encountered. CONCLUSIONS: Placement of fat between a
      parasellar neoplasm and the optic chiasm appears to be a safe approach to help
      define the tumor chiasm space, helping to facilitate radiosurgery. Future
      experience is warranted to determine the efficacy of this technique.

PMID- 25062906
TI  - Mental distress and podoconiosis in Northern Ethiopia: a comparative cross
      sectional study.
AB  - BACKGROUND: The stigma, deformity and disability related to most neglected
      tropical diseases may lead to poor mental health. We aimed to assess the
      comorbidity of podoconiosis and mental distress. METHODS: A comparative cross
      sectional study was conducted in 2012, including 346 people with podoconiosis and
      349 healthy neighbourhood controls. Symptoms of mental distress were assessed
      using the validated Amharic translation of the Kessler-10 scale (K10). A linear
      regression analysis was conducted to identify factors associated with mental
      distress. RESULTS: The mean K10 score was 15.92 (95% CI: 15.27 to 16.57) in
      people with podoconiosis and 14.49 (95% CI: 13.85 to 15.12) in controls (average
      K10 scores 1.43 points higher [95% CI: 0.52 to 2.34]). In multivariate linear
      regression of K10 scores, the difference remained significant when adjusted for
      gender, income, alcohol use, age, place of residence and family history of mental
      illness. In the adjusted model, people with podoconiosis had K10 scores 1.37
      points higher than controls (95% CI: 0.64 to 2.18). Other variables were also
      associated with high K10 scores: women had K10 scores 1.41 points higher than men
      (95% CI: 0.63 to 2.18). Those with family history of mental illness had K10
      scores 3.56 points higher than those without (95% CI: 0.55 to 6.56). CONCLUSIONS:
      This study documented a high burden of mental distress among people with
      podoconiosis compared with healthy controls. Taking this finding in the context
      of the high stigma and reduced quality of life, we recommend integration of
      psychosocial care into the current morbidity management of podoconiosis.

PMID- 25062908
TI  - "If I can get over that, I can get over anything"--understanding how individuals
      with acute whiplash disorders form beliefs about pain and recovery: a qualitative
      study.
AB  - OBJECTIVES: Beliefs held by patients have been shown to influence outcomes in
      acute whiplash associated disorders (WAD). The aim was to identify beliefs about
      pain and recovery present in the narratives of individuals with WAD and to
      understand how and why individuals' came to hold these beliefs. DESIGN: A
      qualitative study. Interpretative Phenomenological Analysis of semi-structured
      interviews. PARTICIPANTS: Participants (n=20) were enrolled in a large, pragmatic
      randomised controlled trial of physiotherapy for acute WAD. Participants were
      interviewed after they completed their treatment. RESULTS: A range of beliefs
      were evident. These included beliefs about exercise and activity, ability to self
      manage symptoms, expectations of recovery and competing priorities. Some beliefs
      appeared to be barriers to recovery despite all participants having consulted
      several health professionals. Health professionals were highly influential over
      how individuals' thought about and managed their injury. The pain experienced
      influenced how individuals thought and behaved as did past experiences of injury
      and illness. Competing priorities were a potential barrier to engaging with
      treatment. We identified examples of how beliefs and behaviour changed in
      response to information from health professionals and the pain they experienced.
      CONCLUSION: People with WAD hold a range of beliefs about pain and recovery and
      some appear unhelpful to recovery. Health professionals can influence these
      beliefs and encourage behaviours that aid recovery. Understanding how patients
      form beliefs may help health professionals to address unhelpful beliefs. It is
      important that advice and education provided is in line with the current
      evidenced based understanding of pain and recovery.

PMID- 25062909
TI  - Active commuting and perceptions of the route environment: a longitudinal
      analysis.
AB  - OBJECTIVE: To assess associations between changes in perceptions of the
      environment en route to work and changes in active commuting. METHODS: 655
      commuters in Cambridge, UK reported perceptions of their commuting route and past
      week commuting trips in postal questionnaires in 2009 and 2010. Associations
      between changes in route perceptions and changes in time spent walking and
      cycling, proportion of car trips, and switching to or from the car on the commute
      were modelled using multivariable regression. RESULTS: Changes in only a few
      perceptions were associated with changes in travel behaviour. Commuters who
      reported that it became less pleasant to walk recorded a 6% (95% CI: 1, 11) net
      increase in car trips and a 12 min/week (95% CI: -1, -24) net decrease in
      walking. Increases in the perceived danger of cycling or of crossing the road
      were also associated with increases in car trips. Increases in the perceived
      convenience of public transport (OR: 3.31, 95% CI: 1.27, 8.63) or safety of
      cycling (OR: 3.70, 95% CI: 1.44, 9.50) were associated with taking up
      alternatives to the car. CONCLUSIONS: Interventions to improve the safety of
      routes and convenience of public transport may help promote active commuting and
      should be evaluated.

PMID- 25062910
TI  - Helicase associated 2 domain is essential for helicase activity of RNA helicase
      A.
AB  - RNA helicase A (RHA), a DExD/H box protein, plays critical roles in a wide
      variety of cellular or viral functions. RHA contains a conserved core helicase
      domain that is flanked by five other domains. Two double-stranded RNA binding
      domains (dsRBD1 and dsRBD2) are at the N-terminus, whereas HA2 (helicase
      associated 2), OB-fold (oligonucleotide- or oligosaccharide-binding fold), and
      RGG (repeats of arginine and glycine-glycine residues) domains are at the C
      terminus. The role of these domains in the helicase activity of RHA is still
      elusive due to the difficulty of obtaining enzymatically active mutant RHA. Here,
      we purified a series of mutant RHAs containing deletions in either N-terminus or
      C-terminus. Analysis of these mutant RHAs reveals that the dsRBDs are not
      required for RNA unwinding, but can enhance the helicase activity by promoting
      the binding of RHA to substrate RNA. In contrast, deletion of C-terminal domains
      including RGG, OB-fold, and HA2 does not significantly affect the binding of RHA
      to substrate RNA. However, HA2 is essential for the RNA unwinding by RHA whereas
      the RGG and OB-fold are dispensable. The results indicate that the core helicase
      domain alone is not enough for RHA to execute the unwinding activity. 

PMID- 25062911
TI  - Structure of Thermoplasma volcanium Ard1 belongs to N-acetyltransferase family
      member suggesting multiple ligand binding modes with acetyl coenzyme A and
      coenzyme A.
AB  - Acetylation and deacetylation reactions result in biologically important
      modifications that are involved in normal cell function and cancer development.
      These reactions, carried out by protein acetyltransferase enzymes, act by
      transferring an acetyl group from acetyl-coenzymeA (Ac-CoA) to various substrate
      proteins. Such protein acetylation remains poorly understood in Archaea, and has
      been only partially described. Information processing in Archaea has been
      reported to be similar to that in eukaryotes and distinct from the equivalent
      bacterial processes. The human N-acetyltransferase Ard1 (hArd1) is one of the
      acetyltransferases that has been found to be overexpressed in various cancer
      cells and tissues, and knockout of the hArd1 gene significantly reduces growth
      rate of the cancer cell lines. In the present study, we determined the crystal
      structure of Thermoplasma volcanium Ard1 (Tv Ard1), which shows both ligand-free
      and multiple ligand-bound forms, i.e.,Ac-CoA- and coenzyme A (CoA)-bound forms.
      The difference between ligand-free and ligand-bound chains in the crystal
      structure was used to search for the interacting residues. The re-orientation and
      position of the loop between beta4 and alpha3 including the phosphate-binding
      loop (P-loop) were observed, which are important for the ligand interaction. In
      addition, a biochemical assay to determine the N-acetyltransferase activity of Tv
      Ard1 was performed using the T.volcanium substrate protein Alba (Tv Alba). Taken
      together, the findings of this study elucidate ligand-free form of Tv Ard1 for
      the first time and suggest multiple modes of binding with Ac-CoA and CoA. 

PMID- 25062912
TI  - D2N: Distance to the native.
AB  - Root-mean-square-deviation (RMSD), of computationally-derived protein structures
      from experimentally determined structures, is a critical index to assessing
      protein-structure-prediction-algorithms (PSPAs). The development of PSPAs to
      obtain 0A RMSD from native structures is considered central to computational
      biology. However, till date it has been quite challenging to measure how far a
      predicted protein structure is from its native - in the absence of a known
      experimental/native structure. In this work, we report the development of a
      metric "D2N" (distance to the native) - that predicts the "RMSD" of any structure
      without actually knowing the native structure. By combining physico-chemical
      properties and known universalities in spatial organization of soluble proteins
      to develop D2N, we demonstrate the ability to predict the distance of a proposed
      structure to within +/-1.5A error with a remarkable average accuracy of 93.6% for
      structures below 5A from the native. We believe that this work opens up a
      completely new avenue towards assigning reliable structures to whole proteomes
      even in the absence of experimentally determined native structures. The D2N tool
      is freely available at http://www.scfbio-iitd.res.in/software/d2n.jsp. 

PMID- 25062913
TI  - Investigating the allosteric reverse signalling of PARP inhibitors with
      microsecond molecular dynamic simulations and fluorescence anisotropy.
AB  - The inhibition of the poly(ADP-ribose) polymerase (PARP) family members is a
      strategy pursued for the development of novel therapeutic agents in a range of
      diseases, including stroke, cardiac ischemia, cancer, inflammation and diabetes.
      Even though some PARP-1 inhibitors have advanced to clinical setting for cancer
      therapy, a great deal of attention is being devoted to understand the
      polypharmacology of current PARP inhibitors. Besides blocking the catalytic
      activity, recent works have shown that some PARP inhibitors exhibit a poisoning
      activity, by trapping the enzyme at damaged sites of DNA and forming cytotoxic
      complexes. In this study we have used microsecond molecular dynamics to study the
      allosteric reverse signalling that is at the basis of such an effect. We show
      that Olaparib, but not Veliparib and HYDAMTIQ, is able to induce a specific
      conformational drift of the WGR domain of PARP-1, which stabilizes PARP-1/DNA
      complex through the locking of several salt bridge interactions. Fluorescence
      anisotropy assays support such a mechanism, providing the first experimental
      evidence that HYDAMTIQ, a potent PARP inhibitor with neuroprotective properties,
      is less potent than Olaparib to trap PARP-1/DNA complex. 

PMID- 25062914
TI  - tmBioC: improving interoperability of text-mining tools with BioC.
AB  - The lack of interoperability among biomedical text-mining tools is a major
      bottleneck in creating more complex applications. Despite the availability of
      numerous methods and techniques for various text-mining tasks, combining
      different tools requires substantial efforts and time owing to heterogeneity and
      variety in data formats. In response, BioC is a recent proposal that offers a
      minimalistic approach to tool interoperability by stipulating minimal changes to
      existing tools and applications. BioC is a family of XML formats that define how
      to present text documents and annotations, and also provides easy-to-use
      functions to read/write documents in the BioC format. In this study, we introduce
      our text-mining toolkit, which is designed to perform several challenging and
      significant tasks in the biomedical domain, and repackage the toolkit into BioC
      to enhance its interoperability. Our toolkit consists of six state-of-the-art
      tools for named-entity recognition, normalization and annotation (PubTator) of
      genes (GenNorm), diseases (DNorm), mutations (tmVar), species (SR4GN) and
      chemicals (tmChem). Although developed within the same group, each tool is
      designed to process input articles and output annotations in a different format.
      We modify these tools and enable them to read/write data in the proposed BioC
      format. We find that, using the BioC family of formats and functions, only
      minimal changes were required to build the newer versions of the tools. The
      resulting BioC wrapped toolkit, which we have named tmBioC, consists of our tools
      in BioC, an annotated full-text corpus in BioC, and a format detection and
      conversion tool. Furthermore, through participation in the 2013 BioCreative IV
      Interoperability Track, we empirically demonstrate that the tools in tmBioC can
      be more efficiently integrated with each other as well as with external tools:
      Our experimental results show that using BioC reduces >60% in lines of code for
      text-mining tool integration. The tmBioC toolkit is publicly available at
      http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/tmTools/. Database URL:
      http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/tmTools/.

PMID- 25062915
TI  - Genome-wide search for eliminylating domains reveals novel function for BLES03
      like proteins.
AB  - Bacterial phosphothreonine lyases catalyze a novel posttranslational modification
      involving formation of dehydrobutyrine/dehyroalanine by beta elimination of the
      phosphate group of phosphothreonine or phosphoserine residues in their substrate
      proteins. Though there is experimental evidence for presence of dehydro amino
      acids in human proteins, no eukaryotic homologs of these lyases have been
      identified as of today. A comprehensive genome-wide search for identifying
      phosphothreonine lyase homologs in eukaryotes was carried out. Our fold-based
      search revealed structural and catalytic site similarity between bacterial
      phosphothreonine lyases and BLES03 (basophilic leukemia-expressed protein 03), a
      human protein with unknown function. Ligand induced conformational changes
      similar to bacterial phosphothreonine lyases, and movement of crucial arginines
      in the loop region to the catalytic pocket upon binding of phosphothreonine
      containing peptides was seen during docking and molecular dynamics studies.
      Genome-wide search for BLES03 homologs using sensitive profile-based methods
      revealed their presence not only in eukaryotic classes such as chordata and fungi
      but also in bacterial and archaebacterial classes. The synteny of these
      archaebacterial BLES03-like proteins was remarkably similar to that of type IV
      lantibiotic synthetases which harbor LanL-like phosphothreonine lyase domains.
      Hence, context-based analysis reinforced our earlier sequence/structure-based
      prediction of phosphothreonine lyase catalytic function for BLES03. Our in silico
      analysis has revealed that BLES03-like proteins with previously unknown function
      are novel eukaryotic phosphothreonine lyases involved in biosynthesis of dehydro
      amino acids, whereas their bacterial and archaebacterial counterparts might be
      involved in biosynthesis of natural products similar to lantibiotics. 

PMID- 25062916
TI  - Gene loss rather than gene gain is associated with a host jump from monocots to
      dicots in the Smut Fungus Melanopsichium pennsylvanicum.
AB  - Smut fungi are well-suited to investigate the ecology and evolution of plant
      pathogens, as they are strictly biotrophic, yet cultivable on media. Here we
      report the genome sequence of Melanopsichium pennsylvanicum, closely related to
      Ustilago maydis and other Poaceae-infecting smuts, but parasitic to a dicot
      plant. To explore the evolutionary patterns resulting from host adaptation after
      this huge host jump, the genome of Me. pennsylvanicum was sequenced and compared
      with the genomes of U. maydis, Sporisorium reilianum, and U. hordei. Although all
      four genomes had a similar completeness in CEGMA (Core Eukaryotic Genes Mapping
      Approach) analysis, gene absence was highest in Me. pennsylvanicum, and most
      pronounced in putative secreted proteins, which are often considered as effector
      candidates. In contrast, the amount of private genes was similar among the
      species, highlighting that gene loss rather than gene gain is the hallmark of
      adaptation after the host jump to the dicot host. Our analyses revealed a trend
      of putative effectors to be next to another putative effector, but the majority
      of these are not in clusters and thus the focus on pathogenicity clusters might
      not be appropriate for all smut genomes. Positive selection studies revealed that
      Me. pennsylvanicum has the highest number and proportion of genes under positive
      selection. In general, putative effectors showed a higher proportion of
      positively selected genes than noneffector candidates. The 248 putative secreted
      effectors found in all four smut genomes might constitute a core set needed for
      pathogenicity, whereas those 92 that are found in all grass-parasitic smuts but
      have no ortholog in Me. pennsylvanicum might constitute a set of effectors
      important for successful colonization of grass hosts. 

PMID- 25062917
TI  - Pogo-like transposases have been repeatedly domesticated into CENP-B-related
      proteins.
AB  - The centromere is a chromatin region that is required for accurate inheritance of
      eukaryotic chromosomes during cell divisions. Among the different centromere
      associated proteins (CENP) identified, CENP-B has been independently domesticated
      from a pogo-like transposase twice: Once in mammals and once in fission yeast.
      Recently, a third independent domestication restricted to holocentric lepidoptera
      has been described. In this work, we take advantage of the high-quality genome
      sequence and the wealth of functional information available for Drosophila
      melanogaster to further investigate the possibility of additional independent
      domestications of pogo-like transposases into host CENP-B related proteins. Our
      results showed that CENP-B related genes are not restricted to holocentric
      insects. Furthermore, we showed that at least three independent domestications of
      pogo-like transposases have occurred in metazoans. Our results highlight the
      importance of transposable elements as raw material for the recurrent evolution
      of important cellular functions. 

PMID- 25062918
TI  - Underreplicated regions in Drosophila melanogaster are enriched with fast
      evolving genes and highly conserved noncoding sequences.
AB  - Many late replicating regions are underreplicated in polytene chromosomes of
      Drosophila melanogaster. These regions contain silenced chromatin and overlap
      long syntenic blocks of conserved gene order in drosophilids. In this report we
      show that in D. melanogaster the underreplicated regions are enriched with fast
      evolving genes lacking homologs in distant species such as mosquito or human,
      indicating that the phylogenetic conservation of genes correlates with
      replication timing and chromatin status. Drosophila genes without human homologs
      located in the underreplicated regions have higher nonsynonymous substitution
      rate and tend to encode shorter proteins when compared with those in the adjacent
      regions. At the same time, the underreplicated regions are enriched with
      ultraconserved elements and highly conserved noncoding sequences, especially in
      introns of very long genes indicating the presence of an extensive regulatory
      network that may be responsible for the conservation of gene order in these
      regions. The regions have a modest preference for long noncoding RNAs but are
      depleted for small nucleolar RNAs, microRNAs, and transfer RNAs. Our results
      demonstrate that the underreplicated regions have a specific genic composition
      and distinct pattern of evolution. 

PMID- 25062919
TI  - Epigenetics and the evolution of Darwin's Finches.
AB  - The prevailing theory for the molecular basis of evolution involves genetic
      mutations that ultimately generate the heritable phenotypic variation on which
      natural selection acts. However, epigenetic transgenerational inheritance of
      phenotypic variation may also play an important role in evolutionary change. A
      growing number of studies have demonstrated the presence of epigenetic
      inheritance in a variety of different organisms that can persist for hundreds of
      generations. The possibility that epigenetic changes can accumulate over longer
      periods of evolutionary time has seldom been tested empirically. This study was
      designed to compare epigenetic changes among several closely related species of
      Darwin's finches, a well-known example of adaptive radiation. Erythrocyte DNA was
      obtained from five species of sympatric Darwin's finches that vary in
      phylogenetic relatedness. Genome-wide alterations in genetic mutations using copy
      number variation (CNV) were compared with epigenetic alterations associated with
      differential DNA methylation regions (epimutations). Epimutations were more
      common than genetic CNV mutations among the five species; furthermore, the number
      of epimutations increased monotonically with phylogenetic distance.
      Interestingly, the number of genetic CNV mutations did not consistently increase
      with phylogenetic distance. The number, chromosomal locations, regional
      clustering, and lack of overlap of epimutations and genetic mutations suggest
      that epigenetic changes are distinct and that they correlate with the
      evolutionary history of Darwin's finches. The potential functional significance
      of the epimutations was explored by comparing their locations on the genome to
      the location of evolutionarily important genes and cellular pathways in birds.
      Specific epimutations were associated with genes related to the bone morphogenic
      protein, toll receptor, and melanogenesis signaling pathways. Species-specific
      epimutations were significantly overrepresented in these pathways. As
      environmental factors are known to result in heritable changes in the epigenome,
      it is possible that epigenetic changes contribute to the molecular basis of the
      evolution of Darwin's finches. 

PMID- 25062920
TI  - Highly variable recombinational landscape modulates efficacy of natural selection
      in birds.
AB  - Determining the rate of protein evolution and identifying the causes of its
      variation across the genome are powerful ways to understand forces that are
      important for genome evolution. By using a multitissue transcriptome data set
      from great tit (Parus major), we analyzed patterns of molecular evolution between
      two passerine birds, great tit and zebra finch (Taeniopygia guttata), using the
      chicken genome (Gallus gallus) as an outgroup. We investigated whether a special
      feature of avian genomes, the highly variable recombinational landscape,
      modulates the efficacy of natural selection through the effects of Hill-Robertson
      interference, which predicts that selection should be more effective in removing
      deleterious mutations and incorporating beneficial mutations in high
      recombination regions than in low-recombination regions. In agreement with these
      predictions, genes located in low-recombination regions tend to have a high
      proportion of neutrally evolving sites and relaxed selective constraint on sites
      subject to purifying selection, whereas genes that show strong support for past
      episodes of positive selection appear disproportionally in high-recombination
      regions. There is also evidence that genes located in high-recombination regions
      tend to have higher gene expression specificity than those located in low
      recombination regions. Furthermore, more compact genes (i.e., those with
      fewer/shorter introns or shorter proteins) evolve faster than less compact ones.
      In sum, our results demonstrate that transcriptome sequencing is a powerful
      method to answer fundamental questions about genome evolution in nonmodel
      organisms. 

PMID- 25062921
TI  - The comb jelly opsins and the origins of animal phototransduction.
AB  - Opsins mediate light detection in most animals, and understanding their evolution
      is key to clarify the origin of vision. Despite the public availability of a
      substantial collection of well-characterized opsins, early opsin evolution has
      yet to be fully understood, in large part because of the high level of divergence
      observed among opsins belonging to different subfamilies. As a result, different
      studies have investigated deep opsin evolution using alternative data sets and
      reached contradictory results. Here, we integrated the data and methods of three,
      key, recent studies to further clarify opsin evolution. We show that the opsin
      relationships are sensitive to outgroup choice; we generate new support for the
      existence of Rhabdomeric opsins in Cnidaria (e.g., corals and jellyfishes) and
      show that all comb jelly opsins belong to well-recognized opsin groups (the Go
      coupled opsins or the Ciliary opsins), which are also known in Bilateria (e.g.,
      humans, fruit flies, snails, and their allies) and Cnidaria. Our results are most
      parsimoniously interpreted assuming a traditional animal phylogeny where
      Ctenophora are not the sister group of all the other animals. 

PMID- 25062922
TI  - Comparative genomics suggests that the human pathogenic fungus Pneumocystis
      jirovecii acquired obligate biotrophy through gene loss.
AB  - Pneumocystis jirovecii is a fungal parasite that colonizes specifically humans
      and turns into an opportunistic pathogen in immunodeficient individuals. The
      fungus is able to reproduce extracellularly in host lungs without eliciting
      massive cellular death. The molecular mechanisms that govern this process are
      poorly understood, in part because of the lack of an in vitro culture system for
      Pneumocystis spp. In this study, we explored the origin and evolution of the
      putative biotrophy of P. jirovecii through comparative genomics and
      reconstruction of ancestral gene repertoires. We used the maximum parsimony
      method and genomes of related fungi of the Taphrinomycotina subphylum. Our
      results suggest that the last common ancestor of Pneumocystis spp. lost 2,324
      genes in relation to the acquisition of obligate biotrophy. These losses may
      result from neutral drift and affect the biosyntheses of amino acids and
      thiamine, the assimilation of inorganic nitrogen and sulfur, and the catabolism
      of purines. In addition, P. jirovecii shows a reduced panel of lytic proteases
      and has lost the RNA interference machinery, which might contribute to its genome
      plasticity. Together with other characteristics, that is, a sex life cycle within
      the host, the absence of massive destruction of host cells, difficult culturing,
      and the lack of virulence factors, these gene losses constitute a unique
      combination of characteristics which are hallmarks of both obligate biotrophs and
      animal parasites. These findings suggest that Pneumocystis spp. should be
      considered as the first described obligate biotrophs of animals, whose evolution
      has been marked by gene losses. 

PMID- 25062923
TI  - Assessment of change in prostate volume and shape following surgical resection
      through co-registration of in-vivo MRI and fresh specimen ex-vivo MRI.
AB  - AIM: To compare the size and shape of the prostate between in-vivo and fresh ex
      vivo magnetic resonance imaging (MRI), in order to quantify alterations in the
      prostate resulting from surgical resection. MATERIAL AND METHOD: Ten patients who
      had undergone 3 T prostate MRI using a phased-array coil and who were scheduled
      for prostatectomy were included in this prospective study. The ex-vivo specimen
      underwent MRI prior to formalin fixation or any other histopathological
      processing. Prostate volume in vivo and ex vivo was assessed using planimetry.
      Prostate shape was assessed by calculating ratios between the diameters of the
      prostate in all three dimensions. RESULTS: Mean prostate volume was significantly
      smaller ex vivo than in vivo (39.7 +/- 18.6 versus 50.8 +/- 26.8 cm(3); p =
      0.008), with an average change in volume of -19.5%. The right-to-left
      (RL)/anteroposterior (AP) ratio of the prostate, representing the shape of the
      prostate within its axial plane, was significantly larger ex vivo than in vivo
      (1.33 +/- 0.14 versus 1.21 +/- 0.12; p = 0.015), with an average percent change
      in RL/AP ratio of the prostate of +12.2%. There was no significant difference
      between in-vivo and ex-vivo acquisitions in terms of craniocaudal (CC)/AP (p =
      0.963, median change = -2.1%) or RL/CC (p = 0.265, median change = +1.3%) ratios.
      CONCLUSION: The observed volume and shape change following resection has not
      previously been assessed by comparison of in-vivo and fresh ex-vivo MRI and
      likely represents loss of vascularity and of connective tissue attachments in the
      ex-vivo state. These findings have implications for co-registration platforms
      under development to facilitate improved understanding of the accuracy of MRI in
      spatial localization of prostate tumours.

PMID- 25062924
TI  - Assessment of renal fibrosis in chronic kidney disease using diffusion-weighted
      MRI.
AB  - AIM: To assess the performance of diffusion-weighted magnetic resonance imaging
      (MRI) for the assessment of renal fibrosis in chronic kidney disease (CKD), with
      histopathology as a reference standard. MATERIALS AND METHODS: Forty patients
      with CKD and 30 healthy volunteers were recruited for the study. All participants
      underwent diffusion-weighted MRI. Renal biopsy was performed in 25 patients with
      CKD. Mean renal medullary and cortical apparent diffusion coefficient (ADC)
      values were compared between CKD patients and the healthy volunteers. Pearson's
      correlation coefficient was calculated to investigate the relationship between
      ADC values, serum creatinine (SCr), estimated glomerular filtration rate (eGFR),
      24 h urinary protein (24h-UPRO), and renal histopathological scores. RESULTS:
      Cortical and medullary ADC values in the CKD group were significantly lower
      compared to those in the healthy controls. In the CKD group, a significant
      negative correlation was found between cortical ADC values and SCr/24h-UPRO, and
      significant positive correlation was found between cortical ADC and eGFR. There
      was also a significant negative correlation between medullary ADC values and SCr.
      Both cortical and medullary ADC values were significantly correlated with
      histopathological fibrosis score. CONCLUSION: Renal ADC values strongly correlate
      with histological measures of fibrosis, and have the potential to enhance the non
      invasive monitoring of chronic kidney disease.

PMID- 25062925
TI  - Surface reconstructions of foetal brain abnormalities using ultrafast steady
      state 3D acquisitions.
AB  - MRI of the foetal brain in utero is performed in routine clinical practice using
      sequences that produce two-dimensional (2D) images. Recent developments in image
      post-processing have allowed the construction of three-dimensional (3D) volume
      data sets from 2D images acquired in different anatomical planes, but these have
      limitations due to the unpredictable nature of foetal movement. These limitations
      have been overcome by development of several different advanced computer
      techniques, which require specialist knowledge, software, and processing methods,
      which are rarely available in routine clinical settings. Our aim was to develop a
      technique that can be used in routine clinical situations without the need for
      custom-developed or expensive software by utilizing MRI sequences that can
      produce a 3D data set in "ultrafast" timescales. The 3D dataset, combined with
      versatile image post-processing and visualization techniques, has resulted in the
      production of high-resolution images of foetal brain surfaces in utero. The aim
      of this paper is to demonstrate our methods and early results by way of a
      pictorial review illustrating a range of developmental brain disease in utero. 

PMID- 25062926
TI  - Pitfalls of adrenal imaging with chemical shift MRI.
AB  - Chemical shift (CS) MRI of the adrenal glands exploits the different precessional
      frequencies of fat and water protons to differentiate the intracytoplasmic lipid
      containing adrenal adenoma from other adrenal lesions. The purpose of this review
      is to illustrate both technical and interpretive pitfalls of adrenal imaging with
      CS MRI and emphasize the importance of adherence to strict technical
      specifications and errors that may occur when other imaging features and clinical
      factors are not incorporated into the diagnosis. When performed properly, the
      specificity of CS MRI for the diagnosis of adrenal adenoma is over 90%. Sampling
      the in-phase and opposed-phase echoes in the correct order and during the same
      breath-hold are essential requirements, and using the first echo pair is
      preferred, if possible. CS MRI characterizes more adrenal adenomas then
      unenhanced CT but may be non-diagnostic in a proportion of lipid-poor adenomas;
      CT washout studies may be able to diagnose these lipid-poor adenomas. Other
      primary and secondary adrenal tumours and supra-renal disease entities may
      contain lipid or gross fat and mimic adenoma or myelolipoma. Heterogeneity within
      an adrenal lesion that contains intracytoplasmic lipid could be due to
      myelolipoma, lipomatous metaplasia of adenoma, or collision tumour. Correlation
      with previous imaging, other imaging features, clinical history, and laboratory
      investigations can minimize interpretive errors. 

PMID- 25062927
TI  - Treating community-acquired pneumonia: to suppress or not to suppress? How much
      or what to suppress with? Those are the questions!

PMID- 25062928
TI  - Dementia: time trends and policy responses.
AB  - In recent years, dementia has been considered a public health priority and become
      a topic of major political interest. Recent reviews and studies have reported
      with varying degrees of alarm an impending and existing "dementia epidemic" with
      increasing predicted trends in prevalence and enormous numbers of people with
      dementia particularly in low- and middle-income countries (LMICs). However,
      robust evidence from dementia research in high-income countries suggests stable
      or decreased prevalence over the last decades. Current evidence is not sufficient
      to suggest increasing trends of prevalence in LMICs once variation in
      methodological factors and study populations are taken into account. Changes in
      diagnostic methods over the last decades substantially influence the
      identification of dementia cases with systematic difference between the resulting
      individual prevalence studies. Potential geographical variations at the country
      level might indicate potential risk factors at population levels or systematic
      difference in clinical application of dementia diagnosis. Although it is
      important and necessary to use information from dementia research for evidence
      based policymaking, over-interpretation of results without carefully considering
      underlying factors could exaggerate the findings and influence policy planning in
      ways which do not serve current and future population best. Planning of dementia
      policy needs to take full cognisance of the provenance of the data being used and
      be integrated with policies which optimise health across the lifecourse. 

PMID- 25062929
TI  - Religious Orientation, Endorser Credibility, and the Portrayal of Female Nurses
      by the Media.
AB  - Medical consumption and media culture in Taiwan contain clear religious elements.
      It is common for people to believe that medicine is a supernatural treatment and
      to rely on thoughts of unseen power instead of rational consciousness. Religious
      influenced patriarchy, seen in cultural gender roles, significantly influences
      religious adherents and degrades women as being part of a secondary class in
      society. As a contradictory tradition, women, in comparison to men, are
      considered best at undertaking certain jobs that require careful, detailed
      thought (such as nurses). Nursing and other occupations requiring a high degree
      of professionalism by women contradict the past religious-based concept of
      "ignorance is a woman's virtue." This study aims to probe female imagery in
      eastern and western Taiwan and explores whether religious culture and practice
      influences people's cognition of female nurses in advertising. The constructs are
      analyzed through structural equation modeling. Results reveal that religious
      followers do not necessarily trust female nurses more just because they are
      portrayed as professional medical specialists. Most consumers reflect this
      negative cognition through purchase intentions of products. For example, in
      comparing portrayals of attractiveness with portrayals of professionalism,
      attractiveness results in a better advertising effect. People with intrinsic or
      extrinsic religious orientation have gradually lowered their negative impressions
      of women; however, religious followers still more strongly insist on women's
      secondary position. Attractive female nurses are more likely judged as reliable,
      and this may be transferred to trust in their professional medical skills. 

PMID- 25062930
TI  - Why do men prefer nice women? Gender typicality mediates the effect of
      responsiveness on perceived attractiveness in initial acquaintanceships.
AB  - Responsiveness may signal to a potential partner that one is concerned with her
      or his welfare, and may therefore increase sexual interest in this person.
      Research shows, however, that this proposition holds true for men, but not for
      women. In three studies, one observational and two experimental, we explored a
      potential mechanism that explains why men and women diverge in their sexual
      reactions to a responsive opposite-sex stranger. Studies 1 and 2 showed that men,
      but not women, perceived a responsive stranger as more gender typical
      (masculine/feminine) and, in turn, as more attractive. Study 3 revealed that
      responsiveness increased men's perception of partner's femininity. This, in turn,
      was associated with higher sexual arousal, which was, in turn, linked to greater
      partner attractiveness and greater desire for a long-term relationship. These
      findings suggest that whether responsiveness affects perceptions of partner
      attractiveness varies in individuals, depending on the contextually based meaning
      of responsiveness.

PMID- 25062931
TI  - The effects of acute oral glutamine supplementation on exercise-induced
      gastrointestinal permeability and heat shock protein expression in peripheral
      blood mononuclear cells.
AB  - Chronic glutamine supplementation reduces exercise-induced intestinal
      permeability and inhibits the NF-kappaB pro-inflammatory pathway in human
      peripheral blood mononuclear cells. These effects were correlated with activation
      of HSP70. The purpose of this paper is to test if an acute dose of oral glutamine
      prior to exercise reduces intestinal permeability along with activation of the
      heat shock response leading to inhibition of pro-inflammatory markers. Physically
      active subjects (N = 7) completed baseline and exercise intestinal permeability
      tests, determined by the percent ratio of urinary lactulose (5 g) to rhamnose (2
      g). Exercise included two 60-min treadmill runs at 70 % of VO2max at 30  degrees
      C after ingestion of glutamine (Gln) or placebo (Pla). Plasma levels of endotoxin
      and TNF-alpha, along with peripheral blood mononuclear cell (PBMC) protein
      expression of HSP70 and IkappaBalpha, were measured pre- and post-exercise and 2
      and 4 h post-exercise. Permeability increased in the Pla trial compared to that
      at rest (0.06 +/- 0.01 vs. 0.02 +/- 0.018) and did not increase in the Gln trial.
      Plasma endotoxin was lower at the 4-h time point in the Gln vs. 4 h in the Pla
      (6.715 +/- 0.046 pg/ml vs. 7.952 +/- 1.11 pg/ml). TNF-alpha was lower 4 h post
      exercise in the Gln vs. Pla (1.64 +/- 0.09 pg/ml vs. 1.87 +/- 0.12 pg/ml). PBMC
      expression of IkBalpha was higher 4 h post-exercise in the Gln vs. 4 h in the Pla
      (1.29 +/- 0.43 vs. 0.8892 +/- 0.040). HSP70 was higher pre-exercise and 2 h post
      exercise in the Gln vs. Pla (1.35 +/- 0.21 vs. 1.000 +/- 0.000 and 1.65 +/- 0.21
      vs. 1.27 +/- 0.40). Acute oral glutamine supplementation prevents an exercise
      induced rise in intestinal permeability and suppresses NF-kappaB activation in
      peripheral blood mononuclear cells. 

PMID- 25062932
TI  - Curvature effect on hemodynamic conditions at the inner bend of the carotid
      siphon and its relation to aneurysm formation.
AB  - Although high-impact hemodynamic forces are thought to lead to cerebral
      aneurysmal change, little is known about the aneurysm formation on the inner
      aspect of vascular bends such as the internal carotid artery (ICA) siphon where
      wall shear stress (WSS) is expected to be low. This study evaluates the effect of
      vessel curvature and hemodynamics on aneurysm formation along the inner carotid
      siphon. Catheter 3D-rotational angiographic volumes of 35 ICA (10 aneurysms, 25
      controls) were evaluated in 3D for radius of curvature and peak curvature of the
      siphon bend, followed by univariate statistical analysis. Computational fluid
      dynamic (CFD) simulations were performed on patient-derived models after aneurysm
      removal and on synthetic variants of increasing curvature. Peak focal siphon
      curvature was significantly higher in aneurysm bearing ICAs (0.36 +/- 0.045 vs.
      0.30 +/- 0.048 mm(-1), p=0.003), with no difference in global radius of curvature
      (p=0.36). In CFD simulations, increasing parametric curvature tightness (from 5
      to 3mm radius) resulted in dramatic increase of WSS and WSS gradient magnitude
      (WSSG) on the inner wall of the bend. In patient-derived data, the location of
      aneurysms coincided with regions of low WSS (<4 Pa) flanked by high WSS and WSSG
      peaks. WSS peaks correlated with the aneurysm neck. In contrast, control siphon
      bends displayed low, almost constant, WSS and WSSG profiles with little spatial
      variation. High bend curvature induces dynamically fluctuating high proximal WSS
      and WSSG followed by regions of flow stasis and recirculation, leading to local
      conditions known to induce destructive vessel wall remodeling and aneurysmal
      initiation.

PMID- 25062933
TI  - High-resolution computational fluid dynamics detects flow instabilities in the
      carotid siphon: implications for aneurysm initiation and rupture?
AB  - The carotid siphon is by nature a tortuous vessel segment with sharp bends and
      large area variations, and of relevance to the study of intracranial aneurysm
      initiation and rupture. The aim of this paper was to determine whether the siphon
      might harbor flow instabilities, if care is taken to resolve them. This study
      focused on five consecutive internal carotid artery (ICA) aneurysm cases from the
      open-source Aneurisk dataset. The aneurysm, always downstream of the siphon, was
      digitally removed using previously developed and verified tools. Computational
      fluid dynamic (CFD) models included long cervical segments upstream, and middle
      and anterior cerebral arteries downstream. High-resolution pulsatile simulations
      were performed using the equivalent of ~24 million linear tetrahedra on average
      (range 16-32 M) and 30,000 time-steps/cycle. Two of the five cases were laminar
      with mild flow instabilities right after peak systole. One of the cases
      experienced strong periodic vortex shedding at a frequency of around 100 Hz. The
      remaining two cases harbored higher frequency flow instabilities and complex 3D
      vortical structures, extending to the cerebral arteries downstream. Our findings
      suggest that the carotid siphon, a conduit to the majority of anterior
      intracranial aneurysms, may experience flow instabilities, consistent with in
      vitro reports, but seemingly at odds with the majority of CFD studies, which have
      been done at lower resolutions. This has obvious implications for elucidating the
      forces involved in aneurysm initiation; and propagation of flow instabilities
      into ICA or downstream aneurysms could also impact understanding of the forces
      involved in aneurysm rupture.

PMID- 25062934
TI  - Indoor tanning in businesses and homes and risk of melanoma and nonmelanoma skin
      cancer in 2 US case-control studies.
AB  - BACKGROUND: Indoor tanning increases skin cancer risk. Beyond early research
      describing melanoma and sun lamps, few recent reports describe where individuals
      indoor tan and whether skin cancer risk varies by location (business, home
      based). OBJECTIVE: We sought to assess where individuals tanned indoors and skin
      cancer risk by tanning device location. METHODS: Multivariate logistic regression
      was conducted in 2 US case-control studies of melanoma (1161 cases, 1083
      controls, ages 25-59 years) and early-onset basal cell carcinoma (375 cases, 382
      controls, age<40 years) conducted between 2004 and 2010. RESULTS: Most indoor
      tanners (86.4%-95.1%), especially younger individuals, tanned exclusively in
      businesses. Persons who used indoor tanning exclusively in businesses were at
      increased risk of melanoma (odds ratio 1.82, 95% confidence interval 1.47-2.26)
      and basal cell carcinoma (odds ratio 1.69, 95% confidence interval 1.15-2.48)
      compared with non-users. Melanoma risk was also increased in the small number who
      reported tanning indoors only at home relative to non-users (odds ratio 4.14, 95%
      confidence interval 1.75-9.78); 67.6% used sun lamps. LIMITATIONS: Self-reported
      tanning and potential recall bias are limitations. CONCLUSION: Business-only
      tanning, despite claims of "safe" tanning, was positively associated with a
      significant risk of melanoma and basal cell carcinoma. Home tanning was uncommon
      and mostly from sun lamps, which were rarely used by younger participants.
      Regardless of location, indoor tanning was associated with increased risk of skin
      cancer.

PMID- 25062935
TI  - Interferons-beta versus glatiramer acetate for relapsing-remitting multiple
      sclerosis.
AB  - BACKGROUND: Interferons (IFNs)-beta and glatiramer acetate (GA) were the first
      two disease-modifying therapies (DMTs) approved 15 years ago for the treatment of
      multiple sclerosis (MS). DMTs prescription rates as first or switching therapies
      and their costs have increased substantially over the past decade. As more DMTs
      become available, the choice of a specific DMT should reflect the risk/benefit
      profile, as well as the impact on quality profile. As MS cohorts enrolled in
      different studies can vary significantly, head-to-head trials are considered the
      best approach for gaining objective reliable data when two different drugs are
      compared. The purpose of this study is to summarise available evidence on the
      comparative effectiveness of IFNs-beta and GA on disease course through a
      systematic review of head-to-head trials. OBJECTIVES: To assess whether IFNs-beta
      and GA differ in terms of safety and efficacy in the treatment of patients with
      relapsing-remitting MS (RRMS). SEARCH METHODS: We searched the Trials Specialised
      Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central
      Nervous System Group (29 October 2013) and the reference lists of retrieved
      articles. We contacted trialists and pharmaceutical companies. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing directly IFNs-beta versus
      GA in study participants affected by RRMS. DATA COLLECTION AND ANALYSIS: We used
      standard methodological procedures as expected by The Cochrane Collaboration.
      MAIN RESULTS: Five trials contributed to this review. A total of 2858
      participants were randomly assigned to IFNs (1679) and GA (1179). The treatment
      duration was three years for one study and two years for the other four RCTs. The
      IFNs analysed in comparison with GA were IFN-beta 1b 250 mcg (two trials, 933
      participants), IFN-beta 1a 44 mcg (two trials, 441 participants) and IFN-beta 1a
      30 mcg (two trials, 305 participants). Enrolled participants were affected by
      active RRMS. All studies were at high risk for attrition bias.Both therapies
      showed similar clinical efficacy at 24 months, given the primary outcome
      variables (number of participants with relapse (risk ratio (RR) 1.04, 95%
      confidence interval (CI) 0.87 to 1.24) or progression (RR 1.11, 95% CI 0.91 to
      1.35)). However at 36 months, evidence from a single study suggests that relapse
      rates were higher in the group given IFNs than in the GA group (RR 1.40, 95% CI
      1.13 to 1.7, P value 0.002).Secondary magnetic resonance imaging (MRI) outcomes
      analysis showed that effects on new or enlarging T2- or gadolinium (Gd)-enhancing
      lesions at 24 months were similar (mean difference (MD) -0.01, 95% CI -0.28 to
      0.26, and MD -0.14, 95% CI -0.30 to 0.02, respectively). However, the reduction
      in T2- and T1-weighted lesion volume was significantly greater in the groups
      given IFNs than in the GA groups (MD -0.58, 95% CI -0.99 to -0.18, P value 0.004,
      and MD -0.20, 95% CI -0.33 to -0.07, P value 0.003, respectively).The number of
      participants who dropped out of the study because of adverse events was similar
      in the two groups (RR 0.95, 95% CI 0.64 to 1.40).The quality of evidence for
      primary outcomes was judged as moderate for clinical end points, but for safety
      and some MRI outcomes (number of active T2 lesions), quality was judged as low.
      AUTHORS' CONCLUSIONS: The effects of IFNs-beta and GA in the treatment of
      patients with RRMS, including clinical (e.g. patients with relapse, risk to
      progression) and MRI (Gd-enhancing lesions) activity measures, seem to be similar
      or to show only small differences. When MRI lesion load accrual is considered,
      the effect of the two treatments differs, in that IFNs-beta were found to limit
      the increase in lesion burden as compared with GA. Evidence was insufficient for
      a comparison of the effects of the two treatments on patient-reported outcomes,
      such as quality of life measures.

PMID- 25062936
TI  - N2O emission from a combined ex-situ nitrification and in-situ denitrification
      bioreactor landfill.
AB  - A combined process comprised of ex-situ nitrification in an aged refuse
      bioreactor (designated as A bioreactor) and in-situ denitrification in a fresh
      refuse bioreactor (designated as F bioreactor) was constructed for investigating
      N2O emission during the stabilization of municipal solid waste (MSW). The results
      showed that N2O concentration in the F bioreactor varied from undetectable to
      about 130 ppm, while it was much higher in the A bioreactor with the
      concentration varying from undetectable to about 900 ppm. The greatly differences
      of continuous monitoring of N2O emission after leachate cross recirculation in
      each period were primarily attributed to the stabilization degree of MSW.
      Moreover, the variation of N2O concentration was closely related to the leachate
      quality in both bioreactors and it was mainly affected by the COD and COD/TN
      ratio of leachate from the F bioreactor, as well as the DO, ORP, and NO3(-)-N of
      leachate from the A bioreactor.

PMID- 25062937
TI  - Investigating the effect of compression on solute transport through degrading
      municipal solid waste.
AB  - The effect of applied compression on the nature of liquid flow and hence the
      movement of contaminants within municipal solid waste was examined by means of
      thirteen tracer tests conducted on five separate waste samples. The conservative
      nature of bromide, lithium and deuterium tracers was evaluated and linked to the
      presence of degradation in the sample. Lithium and deuterium tracers were non
      conservative in the presence of degradation, whereas the bromide remained
      effectively conservative under all conditions. Solute diffusion times into and
      out of less mobile blocks of waste were compared for each test under the
      assumption of dominantly dual-porosity flow. Despite the fact that hydraulic
      conductivity changed strongly with applied stress, the block diffusion times were
      found to be much less sensitive to compression. A simple conceptual model,
      whereby flow is dominated by sub-parallel low permeability obstructions which
      define predominantly horizontally aligned less mobile zones, is able to explain
      this result. Compression tends to narrow the gap between the obstructions, but
      not significantly alter the horizontal length scale. Irrespective of knowledge of
      the true flow pattern, these results show that simple models of solute flushing
      from landfill which do not include depth dependent changes in solute transport
      parameters are justified. 

PMID- 25062938
TI  - Anaerobic co-digestion of food waste and landfill leachate in single-phase batch
      reactors.
AB  - In order to investigate the effect of raw leachate on anaerobic digestion of food
      waste, co-digestions of food waste with raw leachate were carried out. A series
      of single-phase batch mesophilic (35+/-1 degrees C) anaerobic digestions were
      performed at a food waste concentration of 41.8 g VS/L. The results showed that
      inhibition of biogas production by volatile fatty acids (VFA) occurred without
      raw leachate addition. A certain amount of raw leachate in the reactors
      effectively relieved acidic inhibition caused by VFA accumulation, and the system
      maintained stable with methane yield of 369-466 mL/g VS. Total ammonia nitrogen
      introduced into the digestion systems with initial 2000-3000 mgNH4-N/L not only
      replenished nitrogen for bacterial growth, but also formed a buffer system with
      VFA to maintain a delicate biochemical balance between the acidogenic and
      methanogenic microorganisms. UV spectroscopy and fluorescence excitation-emission
      matrix spectroscopy data showed that food waste was completely degraded. We
      concluded that using raw leachate for supplement water addition and pH modifier
      on anaerobic digestion of food waste was effective. An appropriate fraction of
      leachate could stimulate methanogenic activity and enhance biogas production.

PMID- 25062939
TI  - A pyrolysis study for the thermal and kinetic characteristics of an agricultural
      waste with two different plastic wastes.
AB  - In this study, thermochemical conversion of plastic wastes (PET and PVC) together
      with an agricultural waste (hazelnut shell) was investigated. In order to
      determine the thermal and kinetic behaviours, pyrolysis experiments were carried
      out from room temperature to 800  degrees C, with a heating rate of 10  degrees C
      min(-1) in the presence of a N2 atmosphere in a thermogravimetric analyzer. With
      the obtained thermogravimetric data, an appropriate temperature was specified for
      the pyrolysis of biomass-plastic wastes in a fixed-bed reactor. At the second
      step, pyrolysis experiments were carried out at the same conditions with the
      thermogravimetric analyzer, except the final temperature which was up to 500 
      degrees C in this case. After pyrolysis experiments, pyrolysis yields were
      calculated and characterization studies for bio-oil were investigated.
      Experimental results showed that co-pyrolysis has an important role in the
      determination of the pyrolysis mechanism and the process conditions while
      designing/implementing a thermochemical conversion method where biomass-plastic
      materials were preferred as raw materials. 

PMID- 25062940
TI  - Extraocular muscle repositioning and diplopia: associated with ophthalmic plaque
      radiation therapy for choroidal melanoma.
AB  - OBJECTIVE: To evaluate extraocular muscle surgery associated with plaque
      brachytherapy for choroidal melanoma. DESIGN: Single-center retrospective cohort
      study. PARTICIPANTS: Three hundred twenty-nine eyes of 329 consecutive patients
      with clinically diagnosed choroidal melanoma. INTERVENTION: Palladium 103 plaque
      brachytherapy with or without extraocular muscle surgery. MAIN OUTCOME MEASURES:
      Type of muscle surgery required for each tumor location, timing, incidence, and
      duration of diplopia, as well as treatment. RESULTS: Two hundred fifty-four
      patients (n = 254/329; 77.2%) required muscle surgery. One hundred seven patients
      (n = 107/329; 32.5%) required surgery on 2 or more muscles. Of 373 muscles
      repositioned, the lateral rectus muscle (n = 115/373; 30.8%) and inferior oblique
      muscle (n = 70/373; 18.7%) were the most common, correlating to intraocular tumor
      location (P<0.001). Only 6 tumors (n = 6/61; 9.5%) originating from the iris and
      ciliary body required muscle surgery for plaque placement. Of the 312 patients
      with a preoperative visual acuity better than 20/400, diplopia was reported at
      the first postoperative visit by 41 patients (n = 41/312; 13.1%), 2 of whom had
      not undergone muscle surgery. Diplopia resolved spontaneously within 1 month in
      18 patients (n = 18/41; 43.9%), between 1 and 6 months in 12 patients (n = 12/41;
      29.3%), and at more than 6 months in 5 patients (n = 5/41; 12.2%). Among the 312
      patients, persistent diplopia occurred in 6 patients (1.9%), including 1 who had
      not undergone muscle surgery. Treatment was declined in 1 patient, 3 patients (n
      = 3/41; 7.3%) were treated with prisms, and 2 patients (n = 2/41; 4.9%) required
      surgery. CONCLUSIONS: Extraocular muscle surgery frequently is required for
      plaque brachytherapy. Although transient diplopia occurred in 11.2% of patients,
      persistent diplopia occurred in only 1.9% of patients and was treatable.

PMID- 25062941
TI  - Crime and punishment, rehabilitation or revenge: bioethics for prisoners?

PMID- 25062942
TI  - Comparison of two approaches for the classification of 16S rRNA gene sequences.
AB  - The use of 16S rRNA gene sequences for microbial identification in clinical
      microbiology is accepted widely, and requires databases and algorithms. We
      compared a new research database containing curated 16S rRNA gene sequences in
      combination with the lca (lowest common ancestor) algorithm (RDB-LCA) to a
      commercially available 16S rDNA Centroid approach. We used 1025 bacterial
      isolates characterized by biochemistry, matrix-assisted laser
      desorption/ionization time-of-flight MS and 16S rDNA sequencing. Nearly 80 % of
      isolates were identified unambiguously at the species level by both
      classification platforms used. The remaining isolates were mostly identified
      correctly at the genus level due to the limited resolution of 16S rDNA
      sequencing. Discrepancies between both 16S rDNA platforms were due to differences
      in database content and the algorithm used, and could amount to up to 10.5 %. Up
      to 1.4 % of the analyses were found to be inconclusive. It is important to
      realize that despite the overall good performance of the pipelines for analysis,
      some inconclusive results remain that require additional in-depth analysis
      performed using supplementary methods.

PMID- 25062943
TI  - Acinetobacter sp. isolates from emergency departments in two hospitals of South
      Korea.
AB  - A total of 114 Acinetobacter sp. isolates were collected from patients in the
      emergency departments (EDs) of two Korean hospitals. Most isolates belonged to
      the Acinetobacter baumannii complex (105 isolates, 92.1 %). Imipenem resistance
      was found in 39 isolates (34.2 %) of the Acinetobacter sp. isolates, and 6
      colistin-resistant isolates were also identified. Species distribution and
      antimicrobial-resistance rates were different between the two hospitals. In
      addition, two main clones were identified in the imipenem-resistant A. baumannii
      isolates from hospital B, but very diverse and novel genotypes were found in
      those from hospital A. Many Acinetobacter sp. isolates, including the imipenem
      resistant A. baumannii, are considered to be associated with the community. The
      evidence of high antimicrobial resistance and different features in these
      Acinetobacter sp. isolates between the two EDs suggests the need for continuous
      testing to monitor changes in epidemiology.

PMID- 25062944
TI  - Physical activity counseling in medical school education: a systematic review.
AB  - BACKGROUND: Despite a large evidence base to demonstrate the health benefits of
      regular physical activity (PA), few physicians incorporate PA counseling into
      office visits. Inadequate medical training has been cited as a cause for this.
      This review describes curricular components and assesses the effectiveness of
      programs that have reported outcomes of PA counseling education in medical
      schools. METHODS: The authors systematically searched MEDLINE, EMBASE, PsychINFO,
      and ERIC databases for articles published in English from 2000 through 2012 that
      met PICOS inclusion criteria of medical school programs with PA counseling skill
      development and evaluation of outcomes. An initial search yielded 1944 citations,
      and 11 studies representing 10 unique programs met criteria for this review.
      These studies were described and analyzed for study quality. Strength of evidence
      for six measured outcomes shared by multiple studies was also evaluated, that is,
      students' awareness of benefits of PA, change in students' attitudes toward PA,
      change in personal PA behaviors, improvements in PA counseling knowledge and
      skills, self-efficacy to conduct PA counseling, and change in attitude toward PA
      counseling. RESULTS: Considerable heterogeneity of teaching methods, duration,
      and placement within the curriculum was noted. Weak research designs limited an
      optimal evaluation of effectiveness, that is, few provided pre-/post-intervention
      assessments, and/or included control comparisons, or met criteria for
      intervention transparency and control for risk of bias. The programs with the
      most evidence of improvement indicated positive changes in students' attitudes
      toward PA, their PA counseling knowledge and skills, and their self-efficacy to
      conduct PA counseling. These programs were most likely to follow previous
      recommendations to include experiential learning, theoretically based frameworks,
      and students' personal PA behaviors. CONCLUSIONS: Current results provide some
      support for previous recommendations, and current initiatives are underway that
      build upon these. However, evidence of improvements in physician practices and
      patient outcomes is lacking. Recommendations include future directions for
      curriculum development and more rigorous research designs.

PMID- 25062945
TI  - Transcriptome survey of the lipid metabolic pathways involved in energy
      production and ecdysteroid synthesis in the salmon louse Caligus rogercresseyi
      (Crustacea: Copepoda).
AB  - The goal of this study was to identify and analyze the lipid metabolic pathways
      involved in energy production and ecdysteroid synthesis in the ectoparasite
      copepod Caligus rogercresseyi. Massive transcriptome sequencing analysis was
      performed during the infectious copepodid larval stage, during the attached
      chalimus larval stage, and also in female and male adults. Thirty genes were
      selected for describing the pathways, and these were annotated for proteins or
      enzymes involved in lipid digestion, absorption, and transport; fatty acid
      degradation; the synthesis and degradation of ketone bodies; and steroid and
      ecdysteroid syntheses. Differential expression of these genes was analyzed by
      ontogenic stage and discussed considering each stage's feeding habits and
      energetic needs. Copepodids showed a low expression of fatty acid digestion
      genes, reflected by a non-feeding behavior, and the upregulation of genes
      involved in steroid biosynthesis, which was consistent with a pathway for
      cholesterol synthesis during ecdysis. The chalimus stage showed an upregulation
      of genes related to fatty acid digestion, absorption, and transport, as well as
      to fatty acid degradation and the synthesis of ketone bodies, therefore
      suggesting that lipids ingested from the mucus and skin of the host fish are
      metabolized as important sources of energy. Adult females also showed a pattern
      of high lipid metabolism for energy supply and mobilization in relation to
      reproduction and vitellogenesis. Adult females and males revealed different lipid
      metabolism patterns that reflected different energetic needs. This study reports
      for the first time the probable lipid metabolic pathways involved in the energy
      production and ecdysteroid synthesis of C. rogercresseyi. 

PMID- 25062946
TI  - Is it time for a new global classification of multiple sclerosis?
AB  - BACKGROUND: The geographic distribution of multiple sclerosis (MS) is classically
      divided into three zones based on frequency that were established by Kurtzke in
      the early 1970s. In recent years, an increasing number of epidemiological studies
      have shown significantly higher MS prevalence and incidence rates. OBJECTIVE: The
      aim of this study was to review and update the geographic distribution of MS
      using incidence, prevalence and disease duration from the latest epidemiology
      surveys. METHODS: We conducted a systematic review of articles on MS epidemiology
      published between January 1, 1990 and December 31, 2012. RESULTS: MS studies were
      grouped by continent: the Americas, Europe, Asia, Australia/New Zealand, and
      Africa. A total of 101 studies were identified according to the inclusion
      criteria, and 58 reported incidence estimates. Globally, the median estimated
      incidence of MS was 5.2 (range: 0.5-20.6) per 100,000 p-yrs, the median estimated
      prevalence of MS was 112.0 (with a range of 5.2-335) per 100,000 p-yrs, and the
      average disease duration was 20.2 years (range: 7.6-36.2). CONCLUSION: In the
      past few decades, the global prevalence and incidence patterns of MS have changed
      dramatically. Regardless of the reason of increasing prevalence and incidence
      rate, we suggest the need for a novel classification system based on global MS
      disease burden. Adopting such a system would improve economic efficiency and
      prioritization in health policy planning for MS.

PMID- 25062947
TI  - 4Ts scoring with hemofiltration or hemodialysis clotting.

PMID- 25062948
TI  - The effects of low-dose ketamine on the analgesia nociception index (ANI)
      measured with the novel PhysioDolorisTM analgesia monitor: a pilot study.
AB  - The PhysioDolorisTM analgesia monitor assesses nociception effects on the
      autonomic nervous system by analyzing changes in heart rate variability (HRV).
      This non-invasive device analyses ECG signals and determines the analgesia
      nociception index (ANI), allowing for quantitative assessment of the
      analgesia/nociception balance in anesthetized patients. Ketamine, an analgesic
      adjuvant with sympathomimetic properties, has been shown to improve perioperative
      pain management. The purpose of this pilot study was to evaluate whether low-dose
      ketamine, due to its intrinsic effect on the sino-atrial node, affects HRV and,
      therefore, interferes with ANI measurements. This pilot study included 20 women
      undergoing abdominal hysterectomies. Anesthesia and analgesia were maintained
      with sevoflurane and fentanyl respectively, in a standardized manner. Five
      minutes after intubation, 0.5 MUg kg(-1) of intravenous (i.v.) ketamine was
      administered. ANI, bispectral index (BIS), heart rate and blood pressure were
      recorded from the induction of anesthesia until 5 min after skin incision. There
      was not any significant decrease in mean (+/-SD) ANI values after intubation
      (2.11+/-20.11, p=0.35) or i.v. ketamine administration (1.31+/-15.26, p=0.28).
      The mean (+/-SD) reduction in ANI values after skin incision was statistically
      significant (13.65+/-15.44, p=0.01), which is consistent with increased
      nociception. A single i.v. bolus of 0.5 MUg kg(-1) ketamine did not influence the
      ANI values of 20 women under standardized general anesthesia conditions and
      absent noxious stimulation. These results suggest that the ANI derived from the
      PhysioDolorisTM analgesia monitor is feasible under such clinical conditions.

PMID- 25062949
TI  - Breathing is good.

PMID- 25062950
TI  - Cationic screening of charged surface groups (carboxylates) affects electron
      transfer steps in photosystem-II water oxidation and quinone reduction.
AB  - The functional or regulatory role of long-distance interactions between protein
      surface and interior represents an insufficiently understood aspect of protein
      function. Cationic screening of surface charges determines the morphology of
      thylakoid membrane stacks. We show that it also influences directly the light
      driven reactions in the interior of photosystem II (PSII). After laser-flash
      excitation of PSII membrane particles from spinach, time courses of the delayed
      recombination fluorescence (10MUs-10ms) and the variable chlorophyll-fluorescence
      yield (100MUs-1s) were recorded in the presence of chloride salts. At low salt
      concentrations, a stimulating effect was observed for the S-state transition
      efficiency, the time constant of O2-formation at the Mn4Ca-complex of PSII, and
      the halftime of re-oxidation of the primary quinone acceptor (Qa) by the
      secondary quinone acceptor (Qb). The cation valence determined the half-effect
      concentrations of the stimulating salt effect, which were around 6MUM, 200MUM and
      10mM for trivalent (LaCl3), bivalent (MgCl2, CaCl2), and monovalent cations
      (NaCl, KCl), respectively. A depressing high-salt effect also depended strongly
      on the cation valence (onset concentrations around 2mM, 50mM, and 500mM). These
      salt effects are proposed to originate from electrostatic screening of negatively
      charged carboxylate sidechains, which are found in the form of carboxylate
      clusters at the solvent-exposed protein surface. We conclude that the influence
      of electrostatic screening by solvent cations manifests a functionally relevant
      long-distance interaction between protein surface and electron-transfer reactions
      in the protein interior. A relation to regulation and adaptation in response to
      environmental changes is conceivable. 

PMID- 25062952
TI  - Open issues in transcatheter aortic valve implantation. Part 1: patient selection
      and treatment strategy for transcatheter aortic valve implantation.
AB  - An exponential increase in the use of transcatheter aortic valve implantation
      (TAVI) in patients with severe aortic stenosis has been witnessed over the recent
      years. The current article reviews different areas of uncertainty related to
      patient selection. The use and limitations of risk scores are addressed, followed
      by an extensive discussion on the value of three-dimensional imaging for
      prosthesis sizing and the assessment of complex valve anatomy such as degenerated
      bicuspid valves. The uncertainty about valvular stenosis severity in patients
      with a mismatch between the transvalvular gradient and the aortic valve area, and
      how integrated use of echocardiography and computed tomographic imaging may help,
      is also addressed. Finally, patients referred for TAVI may have concomitant
      mitral regurgitation and/or coronary artery disease and the management of these
      patients is discussed. 

PMID- 25062951
TI  - Progression of coronary artery calcification seems to be inevitable, but
      predictable - results of the Heinz Nixdorf Recall (HNR) study.
AB  - AIM: Coronary artery calcification (CAC), as a sign of atherosclerosis, can be
      detected and progression quantified using computed tomography (CT). We develop a
      tool for predicting CAC progression. METHODS AND RESULTS: In 3481 participants
      (45-74 years, 53.1% women) CAC percentiles at baseline (CACb) and after five
      years (CAC5y) were evaluated, demonstrating progression along gender-specific
      percentiles, which showed exponentially shaped age-dependence. Using quantile
      regression on the log-scale (log(CACb+1)) we developed a tool to individually
      predict CAC5y, and compared to observed CAC5y. The difference between observed
      and predicted CAC5y (log-scale, mean+/-SD) was 0.08+/-1.11 and 0.06+/-1.29 in men
      and women. Agreement reached a kappa-value of 0.746 (95% confidence interval:
      0.732-0.760) and concordance correlation (log-scale) of 0.886 (0.879-0.893).
      Explained variance of observed by predicted log(CAC5y+1) was 80.1% and 72.0% in
      men and women, and 81.0 and 73.6% including baseline risk factors. Evaluating the
      tool in 1940 individuals with CACb>0 and CACb<400 at baseline, of whom 242
      (12.5%) developed CAC5y>400, yielded a sensitivity of 59.5%, specificity 96.1%,
      (+) and (-) predictive values of 68.3% and 94.3%. A pre-defined acceptance range
      around predicted CAC5y contained 68.1% of observed CAC5y; only 20% were expected
      by chance. Age, blood pressure, lipid-lowering medication, diabetes, and smoking
      contributed to progression above the acceptance range in men and, excepting age,
      in women. CONCLUSION: CAC nearly inevitably progresses with limited influence of
      cardiovascular risk factors. This allowed the development of a mathematical tool
      for prediction of individual CAC progression, enabling anticipation of the age
      when CAC thresholds of high risk are reached.

PMID- 25062953
TI  - Open issues in transcatheter aortic valve implantation. Part 2: procedural issues
      and outcomes after transcatheter aortic valve implantation.
AB  - This article provides an overview on procedure-related issues and uncertainties
      in outcomes after transcatheter aortic valve implantation (TAVI). The different
      access sites and how to select them in an individual patient are discussed. Also,
      the occurrence and potential predictors of aortic regurgitation (AR) after TAVI
      are addressed. The different methods to quantify AR are reviewed, and it appears
      that accurate and reproducible quantification is suboptimal. Complications such
      as prosthesis-patient mismatch and conduction abnormalities (and need for
      permanent pacemaker) are discussed, as well as cerebrovascular events, which
      emphasize the development of optimal anti-coagulative strategies. Finally, recent
      registries have shown the adoption of TAVI in the real world, but longer follow
      up studies are needed to evaluate the outcome (but also prosthesis durability).
      Additionally, future studies are briefly discussed, which will address the use of
      TAVI in pure AR and lower-risk patients. 

PMID- 25062954
TI  - Transition from an M1 to a mixed neuroinflammatory phenotype increases amyloid
      deposition in APP/PS1 transgenic mice.
AB  - BACKGROUND: The polarization to different neuroinflammatory phenotypes has been
      described in early Alzheimer's disease, yet the impact of these phenotypes on
      amyloid-beta (Abeta) pathology remains unknown. Short-term studies show that
      induction of an M1 neuroinflammatory phenotype reduces Abeta, but long-term
      studies have not been performed that track the neuroinflammatory phenotype.
      METHODS: Wild-type and APP/PS1 transgenic mice aged 3 to 4 months received a
      bilateral intracranial injection of adeno-associated viral (AAV) vectors
      expressing IFNgamma or green fluorescent protein in the frontal cortex and
      hippocampus. Mice were sacrificed 4 or 6 months post-injection. ELISA
      measurements were used for IFNgamma protein levels and biochemical levels of
      Abeta. The neuroinflammatory phenotype was determined through quantitative PCR.
      Microglia, astrocytes, and Abeta levels were assessed with immunohistochemistry.
      RESULTS: AAV expressing IFNgamma induced an M1 neuroinflammatory phenotype at 4
      months and a mixed phenotype along with an increase in Abeta at 6 months.
      Microglial staining was increased at 6 months and astrocyte staining was
      decreased at 4 and 6 months in mice receiving AAV expressing IFNgamma.
      CONCLUSIONS: Expression of IFNgamma through AAV successfully induced an M1
      phenotype at 4 months that transitioned to a mixed phenotype by 6 months. This
      transition also appeared with an increase in amyloid burden suggesting that a
      mixed phenotype, or enhanced expression of M2a and M2c markers, could contribute
      to increasing amyloid burden and disease progression.

PMID- 25062955
TI  - Efficacy of Acinetobacter sp. B9 for simultaneous removal of phenol and
      hexavalent chromium from co-contaminated system.
AB  - The present study shows the feasibility of a newly isolated strain Acinetobacter
      sp. B9 for concurrent removal of phenol and Cr (VI) from wastewater. The
      experiments were conducted in a batch reactor under aerobic conditions.
      Initially, when mineral salt solution was used as the culture medium, the strain
      was found to utilize phenol as sole carbon and energy source while no Cr (VI)
      removal was observed. However, the addition of glucose as co-carbon source
      resulted in the removal of both toxicants. This co-removal efficiency of the
      strain was further improved with nutrient-rich media (NB). Optimum co-removal was
      determined at 188 mg L(-1) of phenol and 3.5 mg L(-1) of Cr (VI) concentrations
      at pH 7.0. Strain B9 followed the orthometabolic pathway for phenol degradation.
      Transmission electron microscopy (TEM) and Fourier transform infrared
      spectroscopy (FT-IR) studies showed sorption of chromium as one of the major
      mechanisms for Cr (VI) removal by B9 cells. Acinetobacter sp. B9 was later on
      checked for bioremediation of real tannery wastewater. After 96 h of batch
      treatment of tannery effluent containing an initial 47 mg L(-1) phenol and 16 mg
      L(-1) Cr (VI), complete removal of phenol and 87 % reduction of Cr (VI) were
      attained, showing high efficiency of the bacterial strain for potential
      application in industrial pollution control.

PMID- 25062957
TI  - Maharashtra state prepares to ban smokeless tobacco use in public places from
      August.

PMID- 25062956
TI  - Changing paradigms in management of metastatic Castration Resistant Prostate
      Cancer (mCRPC).
AB  - Recently, the standard of care for metastatic Castration Resistant Prostate
      Cancer (mCRPC) has changed considerably. Persistent androgen receptor (AR)
      signaling has been identified as a target for novel therapies and reengages the
      fact that AR continues to be the primary target responsible for metastatic
      prostate cancer. Androgen receptor gene amplification and over expression have
      been found to result in a higher concentration of androgen receptors on tumor
      cells, making them extremely sensitive to low levels of circulating androgens.
      Additionally, prostate cancer cells are able to maintain dihydrotestosterone
      (DHT) concentration in excess of serum concentrations to support tumor growth.
      For many years ketoconazole was the only CYP17 inhibitor that was used to treat
      mCRPC. However, significant toxicities limit its use. Newly approved
      chemotherapeutic agents such as Abiraterone (an oral selective inhibitor of
      CYP17A), which blocks androgen biosynthesis both within and outside the prostate
      cancer cells), and enzalutamide (blocks AR signaling) have improved overall
      survival. There are also ongoing phase III trials for Orteronel (TAK- 700), ARN-
      509 and Galeterone (TOK-001), which targets androgen signaling. In this review,
      we will present the rationale for the newly approved hormonal treatments, their
      indications and complications, and we will discuss ongoing trials that are being
      done to improve the efficacy of the approved agents. Finally, we will talk about
      the potential upcoming hormonal treatments for mCRPC. 

PMID- 25062958
TI  - Bidirectional cross-regulation between the endothelial nitric oxide synthase and
      beta-catenin signalling pathways.
AB  - AIMS: beta-catenin has been shown to be regulated by inducible nitric oxide
      synthase (NOS) in endothelial cells. We investigated here whether beta-catenin
      interacts with and regulates endothelial NOS (eNOS) and whether eNOS activation
      promotes beta-catenin signalling. METHODS AND RESULTS: We identified beta-catenin
      as a novel eNOS binding protein in human umbilical vein endothelial cells
      (HUVECs) by mass spectroscopy and western blot analyses of beta-catenin and eNOS
      immunoprecipitates. This was confirmed by in situ proximity ligation assay. eNOS
      activity, assessed by cGMP production and eNOS phosphorylation (Ser1177), was
      enhanced in beta-catenin(-/-) mouse pulmonary endothelial cells (MPECs) relative
      to wild-type MPECs. eNOS activation (using adenosine, salbutamol, thrombin, or
      histamine), or application of an NO donor (spermine NONOate) or cGMP-analogue (8
      bromo-cGMP) caused nuclear translocation of beta-catenin in HUVEC as shown by
      western blotting of nuclear extracts. Exposure to spermine NONOate, 8-bromo-cGMP,
      or sildenafil (a phosphodiesterase type 5 inhibitor) also increased the
      expression of beta-catenin-dependent transcripts, IL-8, and cyclin D1.
      Stimulation of wild-type MPECs with basic fibroblast growth factor (bFGF),
      vascular endothelial growth factor (VEGF), spermine NONOate, 8-bromo-cGMP, or
      sildenafil increased tube length relative to controls in an angiogenesis assay.
      These responses were abrogated in beta-catenin(-/-) MPECs, with the exception of
      that to bFGF which is NO-independent. In C57BL/6 mice, subcutaneous VEGF
      supplemented Matrigel plugs containing beta-catenin(-/-) MPECs exhibited reduced
      angiogenesis compared with plugs containing wild-type MPECs. Angiogenesis was not
      altered in bFGF-supplemented Matrigel. CONCLUSION: These data reveal
      bidirectional cross-talk and regulation between the NO-cGMP and beta-catenin
      signalling pathways.

PMID- 25062959
TI  - Damage of zona pellucida reduces the developmental potential and quality of
      porcine circovirus type 2-infected oocytes after parthenogenetic activation.
AB  - The present aimed to study if porcine circovirus type 2 (PCV2), which adhered to
      zona pellucida (ZP), was able to enter mature porcine oocytes with intact and
      damaged ZP. Four groups, including uninfected ZP-intact oocytes (UOZI),
      uninfected ZP-damaged oocytes (UOZD), PCV2-infected ZP-intact oocytes (POZI), and
      PCV2-infected ZP-damaged oocytes (POZD) were studied. The oocytes were incubated
      with 1 mL minimum essential medium, containing 3.1 * 10(8) copies of PCV2 DNA for
      1 hour. Mechanical procedure of the insertion by microneedle induced injuries to
      the ZP of porcine oocytes. At the blastocyst stage, the percentage of PCV2
      infected embryos and the ratio of viral antigen-positive cells per embryo were
      determined by indirect immunofluorescence. To assess the effect of ZP injury on
      the developmental competence and quality of porcine PCV2-infected oocytes after
      parthenogenetic activation, blastocyst formation rates and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      staining were analyzed. Moreover, real-time polymerase chain reaction was used to
      evaluate the expression of genes related to apoptosis and pluripotency at
      different developmental stages. The results of indirect immunofluorescence showed
      that only POZD group presented PCV2-infected embryos and viral-positive cells.
      The blastocyst rate of POZD group dropped down to approximately half of POZI
      group's (7.1 +/- 1.5 vs. 14.5 +/- 3.3). At the blastocyst stage, ZP injury
      increased apoptotic index of PCV2-infected embryos. The relative expression
      levels of Caspase 3 were higher in POZD group than the ones in POZI group at the
      two- and four-cell stages (not statistically significant). Compared with the one
      in POZI group, the ratio of antiapoptotic Bcl-xl gene to proapoptotic Bax gene,
      an indicator of the ability to resist apoptosis, was lower in POZD group at the
      one-cell stage, but higher at the two- and four-cell stages. Expression levels of
      Oct4 and Nanog associated with pluripotency were lower in POZD group than the
      ones in POZI group at the morula stage (not statistically significant).
      Noteworthily, the expression of Nanog was significantly lower in POZD group
      versus POZI group (P < 0.05), whereas relative expression of Oct4 was
      significantly higher in the former at the blastocyst stage (P < 0.01). In
      conclusion, PCV2, which attached to ZP, was able to enter mature porcine oocytes
      with damaged ZP and subsequently reduced the developmental competence and quality
      of the oocytes after parthenogenetic activation.

PMID- 25062960
TI  - Somatic diseases and conditions before the first diagnosis of schizophrenia: a
      nationwide population-based cohort study in more than 900 000 individuals.
AB  - OBJECTIVE: Schizophrenia is associated with excess physical comorbidity. Yet, to
      our knowledge, large studies are lacking on the associations with somatic
      diseases before the onset of schizophrenia. The authors conducted a nationwide
      study of the full spectrum of treated somatic diseases before the first diagnosis
      of schizophrenia. METHOD: Nationwide sample of the Danish population consisting
      of singletons (n = 954351) born 1977-1993 and followed from birth to 2009, during
      which period 4371 developed schizophrenia. Somatic diagnoses at all general
      hospital contacts (admitted or outpatient care at a somatic hospital) from 1977
      to 2009 were used as exposures. The incidence rate ratio (IRR) of schizophrenia
      was calculated using Poisson regression adjusted for confounders. RESULTS: Among
      the 4371 persons who developed schizophrenia from 1992 to 2009, a total of 4180
      (95.6%) persons had a previous somatic hospital contact. A history of any somatic
      hospital contact was associated with an elevated risk of schizophrenia (IRR =
      2.04, 95% CI = 1.77-2.37). A wide range of somatic diseases and conditions were
      associated with an increased risk of schizophrenia, including epilepsy (IRR =
      2.26, 95% CI = 1.93-2.62), nutritional or metabolic disorders (IRR = 1.57, 95% CI
      = 1.39-1.77), circulatory system diseases (IRR = 1.63, 95% CI= 1.38-1.92), and
      brain injury (IRR = 1.58, 95% CI = 1.45-1.72). CONCLUSIONS: A wide range of
      potential etiological factors could have contributed to the observed
      associations, including genetic or physiological overlaps between conditions, and
      interacting immunological, behavioral, and neurodevelopmental factors.

PMID- 25062961
TI  - Impact of disclosure of individual imaging results in a multi-center Parkinson
      clinical trial.
AB  - BACKGROUND: Little is known about the impact of providing individual research
      results to clinical trial participants or the impact of sharing such data.
      OBJECTIVE: The objective of this follow-up study was to evaluate the desire of
      participants for learning their imaging results and the impact of this
      information on their perception of their PD diagnosis and care. METHODS: The
      Parkinson Research Examination of CEP-1347 Trial (PRECEPT) evaluated the
      experimental treatment CEP-1347 obtaining dopamine transporter imaging at
      baseline and 22 months as a secondary outcome. Dopamine transporter imaging and
      results were categorized as 'dopamine transporter deficit', 'no dopamine
      transporter deficit' or 'indeterminate.' Self-administered surveys were provided
      on three occasions to subjects who chose to learn their dopamine transporter
      imaging results: prior to receiving imaging data, immediately following receipt
      of imaging information, and three months following image disclosure. RESULTS:
      656/777 subjects (84.4%) consented to receive their individual imaging data,
      comprising overall result categories of 86.3% 'dopamine transporter deficit',
      10.4% 'no dopamine transporter deficit', and 3.4% 'indeterminate.' 99.6% of
      subjects believed their decision to receive data was correct. Following
      disclosure of imaging results, 97% of the 'dopamine transporter deficit' and
      'indeterminate' subjects believed they had Parkinson disease compared with 34% of
      'no dopamine transporter deficit' subjects. About 45% of participants reported
      that learning individual imaging data resulted in improved understanding of their
      diagnosis. CONCLUSION: The majority of research participants chose to learn their
      individual dopamine transporter imaging results and were satisfied with their
      decision. Disclosure of imaging information resulted in improved understanding of
      parkinsonian symptoms in nearly half of subjects, and less belief among 'no
      dopamine transporter deficit' subjects that they had a diagnosis of Parkinson
      disease.

PMID- 25062962
TI  - HLA sensitisation: can it be prevented?
AB  - Human leukocyte antigen (HLA) sensitisation occurs after transfusion of blood
      products and transplantation. It can also happen spontaneously through cross
      sensitisation from infection and pro-inflammatory events. Patients who are highly
      sensitised face longer waiting times on organ allocation programmes, more graft
      rejection and therefore more side effects of immunosuppression, and poorer graft
      outcomes. In this review, we discuss these issues, along with the limitations of
      modern HLA detection methods, and potential ways of decreasing HLA antibody
      development. We do not discuss the removal of antibodies after they have
      developed. 

PMID- 25062963
TI  - Biologics in renal transplantation.
AB  - The biologics used in transplantation clinical practice include several
      monoclonal and polyclonal antibodies aimed at specific cellular receptors. The
      effect of their mechanisms of action includes depleting or blocking specific cell
      subpopulations, complement system, or removing circulating preformed antibodies
      and blocking their production. They are used in induction, desensitization ABO
      incompatible renal transplantation, rescue therapy of steroid-resistant acute
      rejection, treatment of posttransplant recurrence of primary disease such as
      nephrotic syndrome or atypical hemolytic-uremic syndrome, and in late humoral
      rejection. There are various indications for the use of biologic agents before
      and early or late after renal transplantation in both high- and low-risk
      recipients. In the latter situation, the biologics-based induction is used to
      further minimize immunosuppression maintenance. The targets of several biologic
      agents are present across a variety of cells, and manipulation of the immune
      system with biologics may be associated with significant risk of acute and late
      onset adverse events; therefore, clinical risk-versus-benefit ratio must be
      carefully balanced in every case. Several trials on novel biologics are reported
      in adults but not in the pediatric population. 

PMID- 25062964
TI  - Correlation between gene expression and mutator phenotype predicts homologous
      recombination deficiency and outcome in ovarian cancer.
AB  - New strategies are needed to predict response to platinum-based chemotherapy and
      outcome of ovarian cancers. We hypothesized that the mutator phenotype in the
      cancer genome represents the overuse of alternative DNA repair mechanisms, which
      might be a sign of homologous recombination (HR) deficiency and can be captured
      by gene expression. Multidimensional data of ovarian cancer patients and breast
      cancer patients from The Cancer Genome Atlas (TCGA) database were used for the
      development and validation of a potential clinical information-independent score
      that correlates with HR deficiency and predicts outcome. Correlation of the score
      with platinum response, outcome, and BRCA mutations was assessed. The score
      correlated with increased genomic mutation rate in both ovarian cancer and breast
      cancer cases that harbored a substantial subset of HR-deficient samples.
      Significantly improved outcomes were observed in the high-scoring group versus
      the low-scoring group in the TCGA dataset and in three large gene expression
      microarray datasets. A strong correlation was found between the score and the
      likelihood of achieving complete response to chemotherapy. The score was also
      found to be highly robust to noises in genomic mutations. Sixty-four patients
      harboring BRCA mutations were successfully divided into two groups based on
      scores, with the high-scoring group showing significantly improved outcomes
      compared with wild-type cases and the low-scoring group showing no significance
      in all the same analyses. The score was significantly correlated with the
      response to platinum therapy and outcome. Evaluation of the score as a prognostic
      tool in ovarian cancer patients is warranted. KEY MESSAGE: We develop a
      diagnostic signature for the HR-deficiency based on a novel hypothesis. HR
      deficiency score is significantly correlated to platinum therapy and outcomes.
      HRDS was validated by its association with OS, PFS, DFS and CR in validation
      datasets. Evaluation of the score as a prognostic tool in ovarian cancer patients
      is warranted.

PMID- 25062965
TI  - Compliance to step count and vegetable serve recommendations mediates weight gain
      prevention in mid-age, premenopausal women. Findings of the 40-Something RCT.
AB  - The 40-Something RCT aimed to determine if a 12-month health professional-led
      intervention could modify diet and physical activity behaviour for obesity
      prevention, in 44-50 year old, non-obese (BMI = 18.5-29.9 kg/m(2)) premenopausal
      women. Women were monitored for an additional 12 months to determine if effects
      could be maintained. This paper aimed to explore dietary and physical activity
      behavioural mediators hypothesised to be causally associated with weight change.
      Fifty-four women were randomised to a Motivational Interviewing Intervention (MI)
      (n = 28; five health professional consultations) or a Self-Directed Intervention
      (n = 26; written advice). Compliance to 10 study recommendations was measured at
      three months by a four-day weighed food and physical activity record including
      pedometer-measured step counts, self-reported exercise minutes and sitting time.
      The 10 compliance scores were independently assessed in mediation models for 12-
      and 24-month weight change. The MI effect on step count was an increase of 0.99
      points on the 10-point compliance scale (p <= 0.01). This MI effect on step count
      significantly mediated the 12 and 24 month effect on weight (12 months AB = 
      0.74, 95%CI = -1.95, -0.14; 24 months AB = -1.06, 95% CI = -2.56, -0.36),
      accounting for 37.23% and 53.79% of the effect, respectively. The MI effect on
      vegetable serves was an increase of 1.50 points on the compliance scale (p =
      0.02). The MI effect on vegetable compliance significantly mediated the effect on
      weight at 24 months (AB = -0.54, 95% CI = -1.50, -0.04), accounting for 24.92% of
      the effect. The remaining eight dietary and physical activity compliance scores
      did not significantly mediate weight loss. Encouraging women to take 10,000 steps
      and eat five vegetable serves per day may be a promising strategy to achieve long
      term weight control at mid-life.

PMID- 25062966
TI  - Getting to the right metrics.

PMID- 25062967
TI  - Alcohol withdrawal syndrome in admitted trauma patients.
AB  - BACKGROUND: As alcohol use is highly prevalent in trauma patients, we
      hypothesized that a significant proportion of hospitalized trauma patients would
      demonstrate alcohol withdrawal (AW). METHODS: The trauma registries at a joint
      trauma center system from 1999 to 2008 were evaluated for patients aged at least
      16 years. RESULTS: Of 19,369 trauma admissions, 159 patients had AW. Blood
      alcohol concentration (BAC) testing was performed in 31.5% of the patients. BAC
      was significantly higher in AW patients versus other traumas (205.7 +/- 130.1 vs
      102.9 +/- 121.7 mg/dL). BAC was 0 in 14.4% of AW patients. As compared with other
      trauma patients, patients with AW had a significantly greater age (50.2 vs 42.1
      years), hospital length of stay (10 vs 3 days), intensive care unit length of
      stay (2 vs 0 days), need for mechanical ventilation (34% vs 12.7%), and pneumonia
      (12% vs 2.3%). AW patients were less frequently discharged to home (59.8% vs
      69.9%). Mortality was not different. CONCLUSIONS: AW was diagnosed in few
      patients. Of note, it occurred in patients with an initial BAC of 0. AW is
      associated with adverse outcomes.

PMID- 25062968
TI  - Effects of olanzapine-fluoxetine combination treatment of major depressive
      disorders on the quality of life during acute treatment period.
AB  - The objective of the study was to explore the effects of olanzapine-fluoxetine
      combination (OFC) treatment of major depressive disorders on the quality of life
      in the acute treatment period. Methods were prospective and observational design.
      One hundred and three patients of major depressive disorders were observed. One
      group of 53 patients received OFC treatment (OFC group); the other group of 50
      patients received the treatment of duloxetine (duloxetine group). Two groups were
      needed to be observed 8 weeks. Observed indicators were Hamilton Depression
      Rating Scale for Depression (HAMD-24) and four factor scores: the slow, sleep
      disorders, anxiety/somatization, and hopelessness, Clinical Global Impression
      Severity of Illness (CGI-S), WHO quality of life scale (WHOQOL-BREF), and sub
      rate measurements. HAMD-24 and four factor scores observation time were assessed
      before and after treatment; 1, 2, 4, 8 weeks, WHOQOL-BREF score, and sub-time
      measurements were assessed before treatment and 8 weeks after treatment. HAMD-24
      scores of OFC patients in the first week were significantly lower than those of
      the duloxetine group. The sleep factor scores of OFC patients were significantly
      lower than those of the duloxetine group in 4 and 8 weeks. By the end of 8 weeks,
      OFC group was rated significantly lower than the duloxetine group in the physical
      area. In the acute treatment period, OFC treatment effected faster than the
      single duloxetine in patients with major depressive disorders. OFC effected
      within 1 week and was better than the single duloxetine in improving the sleep
      and physical conditions.

PMID- 25062969
TI  - Non-syndromic hereditary gingival fibromatosis in three Chinese families is not
      due to SOS1 gene mutations.
AB  - Non-syndromic hereditary gingival fibromatosis (HGF) is a rare condition,
      characterized by a progressive gingival hyperplasia that occurs as an isolated
      disease. Hitherto, only one insertion (g.126,142-126,143insC) in son-of-sevenless
      1 (SOS1) gene has been associated with non-syndromic HGF in a Brazilian family.
      The aim of the present study was to determine if SOS1 is the causative gene of
      non-syndromic HGF in the Chinese population. Peripheral blood samples were
      collected from six affected and seven unaffected individuals from three Chinese
      families with history of non-syndromic HGF. Genomic DNA was extracted and SOS1
      gene exons were sequenced. Neither g.126,142-126,143insC nor any other novel
      mutation was detected in SOS1 gene. Our results suggest that the SOS1 may not be
      the gene responsible for HGF in these three Chinese families and, therefore, it
      is possible that other genes are involved in the manifestation of HGF in these
      Chinese HGF families. 

PMID- 25062970
TI  - Apolipoprotein E genotyping in women with recurrent pregnancy loss: an in silico
      and experimental hybrid study.
AB  - The role of apolipoprotein E gene polymorphisms in the pathogenesis of recurrent
      pregnancy loss remains controversial. Therefore, our objective was to investigate
      the association between recurrent pregnancy loss and apolipoprotein E gene
      polymorphisms among northwest Iranian women, and also to predict the impact of
      these nonsynonymous single nucleotide polymorphisms on structure and function of
      apolipoprotein E protein. The subjects of our current study consisted of 100
      women that have had two or more consecutive idiopathic first trimester
      miscarriages, and one hundred healthy women from the same geographical areas were
      used as a control group. After DNA extraction, we used a polymerase chain
      reaction-restriction fragment length polymorphism to genotype of the
      apolipoprotein E gene. In addition, we predicted the possible effects of amino
      acid substitutions at codons 112 and/or 158 on the structure and function of
      apolipoprotein E protein using Polymorphism Phenotyping online software v2. Our
      results showed that the rate of apolipoprotein E epsilon4 carriers and the
      frequency of the epsilon4 allele in the case group were statistically and
      significantly higher than those in the control group (P<0.05). Therefore, our
      data support the association of the Apo epsilon4 allele with RPL; however, in
      silico analysis predicted that the amino acid substitution at residue 112 (Apo
      epsilon4 allele) is a benign mutation. Accordingly, further studies are required
      to elucidate the mechanism(s) underlying the link between RPL pathogenesis and
      the Apo epsilon4 allele.

PMID- 25062971
TI  - A role for IL-10 in the transcriptional regulation of Roquin-1.
AB  - Roquin-1, a RING finger E3 ubiquitin ligase, functions as a modulator of
      inflammation; however, nothing is known about how Rc3h1 expression is regulated.
      Here, we describe an opposing relationship between Roquin-1 and the IL-17
      proinflammatory cytokine by demonstrating that enforced expression of Rc3h1
      restricts Il17a expression, and that exposure of T cells to IL-10, a cytokine
      with immunosuppressive activity, increases Rc3h1 expression. Luciferase reporter
      assays conducted using eight transcription factor plasmids (STAT1, STAT3, STAT5,
      GATA2, c-Rel, IKZF1, IKZF2, and IKZF3) demonstrated that STAT1, STAT3, GATA2, and
      c-Rel increased Rc3h1 promoter activity, whereas IKZF2 decreased activity. Gene
      expression of those five transcription factors increased in T cells exposed to IL
      10. Transcription factor-specific siRNAs suppressed the IL-10 effect on Rc3h1
      transcription. These findings identify a role for IL-10 in regulating Rc3h1
      transcription, and they have implications for understanding how Roquin-1 controls
      the immune response.

PMID- 25062972
TI  - Predicting psychosis and psychiatric hospital care among adolescent psychiatric
      patients with the Prodromal Questionnaire.
AB  - The Prodromal Questionnaire (PQ) identifies psychiatric help-seekers in need of
      clinical interviews to diagnose psychosis risk. However, some providers use the
      PQ alone to identify risk. Therefore, we tested its predictive utility among 731
      adolescent psychiatric help-seekers, with a 3-9-year register-based follow-up.
      Nine latent factors corresponded well with postulated subscales.
      Depersonalization predicted later hospitalization with a psychosis diagnosis (HR
      1.6 per SD increase), and Role Functioning predicted any psychiatric
      hospitalization (HR 1.3). Published cut-off scores were poor predictors of
      psychosis; endorsement rates were very high for most symptoms. Therefore, we do
      not recommend using the PQ without second-stage clinical interviews. 

PMID- 25062974
TI  - Methylphenidate misuse in adult patients and the impact of therapeutic use.
AB  - OBJECTIVE: Methylphenidate (MPH) prescription rates for adults increase, but the
      extent of a parallel rise in toxic exposures and their causes and distribution
      between different MPH trade names are unexplored. METHOD: We retrospectively
      analyzed adult MPH exposures reported to the Danish Poison Information Centre
      from January 2006 to July 2012 and the association with MPH sales and the number
      of patients prescribed MPH. RESULTS: Of the 394 exposures (57% males, median age
      27 years) reported, MPH status was available in 249 of whom 65.5% were prescribed
      MPH. Exposure was in 54% motivated by suicidal attempt and in 40% by recreational
      use (based on 375 cases). Exposure was dominated by one trade name and exposure
      incidence correlated significantly with sales ( p = 0.001) and prevalence of MPH
      treated patients ( p = 0.0008). CONCLUSIONS: The increase in MPH exposures
      parallels the prescription rates (particularly Ritalin((r))/Ritalin((r)) Uno).
      Most exposures were intentional and motivated by suicide attempts or recreational
      use.

PMID- 25062973
TI  - The PSI family of nuclear proteins is required for growth in arabidopsis.
AB  - PSI1 was identified as a gene that is co-expressed with the phytosulfokine (PSK)
      receptor genes PSKR1 and PSKR2 in Arabidopsis thaliana. It represents a plant
      specific protein family of unknown function with six members in two clades. Clade
      1 members PSI1, PSI2 and PSI3 were characterized in this study. All three are
      nuclear localized. A predicted N-terminal myristoylation site was functionally
      analyzed. psi1-1 seedlings have shorter roots and hypocotyls. This growth
      retarded phenotype was restored by expression of either wildtype PSI1 or PSI1 G2A
      with a mutated myristate attachment site in the psi1-1 background suggesting that
      myristate attachment was not essential for PSI1 function. psi2-1 and psi3-1
      seedlings have a wildtype phenotype but overexpression of PSI1 or PSI2 promoted
      seedling growth. PSI2 activity appears to be linked to PSK signaling as psi2-1
      and psi2-1 psi3-1 roots are unresponsive to PSK. PSI3 functions in vegetative
      plant growth synergistic with PSI2. psi3-1 and particularly psi2-1 psi3-1
      rosettes are small. Overexpression of PSI3 promoted plant growth indicating that
      PSI3 is limiting at the vegetative stage. Severe dwarfism of psi2-1 psi3-1 plants
      results from reduced cell growth and proliferation and premature leaf growth
      arrest. Plants further display reduced fertility and premature senescence
      revealing a crucial function of PSI proteins in vegetative growth and
      reproduction. Psi single and double knock-out plants have less and PSI3ox plants
      have more starch compared to wt and growth retardation is partially rescued by
      sucrose. Our studies reveal a crucial function of the nuclear-localized PSI
      proteins in growth possibly through metabolic control.

PMID- 25062975
TI  - Neuroleptics and enrichment environment treatment in memory disorders and other
      central nervous system function observed in prenatally stressed rats.
AB  - It is believed that the most effective method of treatment in schizophrenia is
      pharmacotherapy, in particular, the use of atypical neuroleptics like
      aripiprazole (ARI) and olanzapine (OLA). Moreover, studies of many authors have
      shown that enriched living conditions and tobacco smoke exposure can also affect
      the cognitive functions that are disturbed in the course of schizophrenia. The
      aim of the study was to find whether tobacco smoke and enrichment living
      conditions have the influence on cognitive functions in the newborn offspring of
      prenatally stressed rats and whether drugs such as ARI (1.5 mg/kg
      intraperitoneally (i.p.)) and OLA (0.5 mg/kg ip) in single and chronic treatment
      modify those functions (Morris water maze). The study (in the same conditions)
      also analyses immobility time (Porsolt test) and motor activity of animals that
      received ARI and OLA. It has been shown that ARI and OLA as well as enriched
      environment reduce cognitive function disorders and modify cognitive functions in
      rats exposed to tobacco smoke. In turn, current research has shown that nicotine
      has increased cognitive function disorders compared to the previous study
      (animals without tobacco smoke exposure). 

PMID- 25062976
TI  - Diallyl trisulfide ameliorates arsenic-induced hepatotoxicity by abrogation of
      oxidative stress, inflammation, and apoptosis in rats.
AB  - The present study investigates the possible ameliorative effects of diallyl
      trisulfide (DATS) against arsenic (As)-induced hepatotoxicity and oxidative
      stress in rats. The four experimental groups evaluated include: (1) vehicle
      control; (2) As (5 mg/kg/day); (3) DATS (80 mg/kg/day) + As; and (4) DATS.
      Induction of As in rats caused severe hepatotoxicity as evidenced by an elevation
      of serum aspartate aminotransferase and alanine aminotransferase activities and
      increased total bilirubin concentration, indicating hepatic function
      abnormalities. Histopathological examination revealed various structural changes
      in the liver, characterized by hepatocyte degeneration/necrosis, congestion,
      sinusoidal dilatation, vacuolation, and inflammatory cell infiltration. The
      significant decrease in reduced glutathione content, catalase, superoxide
      dismutase, glutathione peroxidase, and glutathione reductase activities and the
      significant increase in lipid peroxidation (thiobarbituric acid reactive
      substance) and protein oxidation (protein carbonyl) contents indicated that As
      induced hepatotoxicity was mediated through oxidative stress. As intoxication
      also elevated the levels of Cas-3 and nitric oxide and increased the expression
      of nuclear factor-kappaB p65 in the liver. In contrast, DATS pretreatment
      significantly improved As-induced serum biochemical, immunohistochemical, and
      histopathological alterations reflecting hepatic dysfunction. These results may
      contribute to a better understanding of the hepatoprotective role of DATS,
      emphasizing the influence of this garlic trisulfide in the diet for human health,
      possibly preventing the hepatic injury associated with As intoxication,
      presumably due to its ability to inhibit lipid peroxidation, protein oxidation,
      and restoration of antioxidant status. 

PMID- 25062977
TI  - Traditional burn care in sub-Saharan Africa: a long history with wide acceptance.
AB  - Burns are very common in sub-Saharan Africa and are considered to be a major
      health care problem. The management of burns in many African countries is
      challenged by limited financial resources, inaccessible health care facilities,
      lack of trained professionals and superstition. These limitations are related to
      the many burned patients seeking treatment from traditional healers. The use of
      traditional remedies, plant and animal products are seen as an important aspect
      of burn management as it is both an affordable and respected treatment modality.
      Despite its popularity, the use of traditional burn care remedies is faced with
      many challenges as little research has been done on its effectiveness, dosage and
      adverse reactions. This paper reviewed the traditions and customs associated with
      traditional burn care as well as the use of plant, animal and mineral products
      used by traditional healers. 

PMID- 25062980
TI  - Enhancing HMM-based protein profile-profile alignment with structural features
      and evolutionary coupling information.
AB  - BACKGROUND: Protein sequence profile-profile alignment is an important approach
      to recognizing remote homologs and generating accurate pairwise alignments. It
      plays an important role in protein sequence database search, protein structure
      prediction, protein function prediction, and phylogenetic analysis. RESULTS: In
      this work, we integrate predicted solvent accessibility, torsion angles and
      evolutionary residue coupling information with the pairwise Hidden Markov Model
      (HMM) based profile alignment method to improve profile-profile alignments. The
      evaluation results demonstrate that adding predicted relative solvent
      accessibility and torsion angle information improves the accuracy of profile
      profile alignments. The evolutionary residue coupling information is helpful in
      some cases, but its contribution to the improvement is not consistent.
      CONCLUSION: Incorporating the new structural information such as predicted
      solvent accessibility and torsion angles into the profile-profile alignment is a
      useful way to improve pairwise profile-profile alignment methods.

PMID- 25062981
TI  - Ayurvedic interventions for osteoarthritis: a systematic review and meta
      analysis.
AB  - Ayurveda is one of the fastest growing systems within complementary and
      alternative medicine. However, the evidence for its effectiveness is
      unsatisfactory. The aim of this work was to review and meta-analyze the
      effectiveness and safety of different Ayurvedic interventions in patients with
      osteoarthritis (OA). 138 electronic databases were searched through August 2013.
      Randomized controlled trials, randomized crossover studies, cluster-randomized
      trials, and non-randomized controlled clinical trials were eligible. Adults with
      pre-diagnosed OA were included as participants. Interventions were included as
      Ayurvedic if they were explicitly labeled as such. Main outcome measures were
      pain, physical function, and global improvement. Risk of bias was assessed using
      the Cochrane risk of bias tool. 19 randomized and 14 non-randomized controlled
      trials on 12 different drugs and 3 non-pharmaceutical interventions with a total
      of 2,952 patients were included. For the compound preparation, Rumalaya, large
      and apparently unbiased effects beyond placebo were found for pain (standardized
      mean difference [SMD] -3.73; 95 % confidence interval [CI] -4.97, -2.50; P <
      0.01) and global improvement (risk ratio 12.20; 95 % CI 5.83, 25.54; P < 0.01).
      There is also some evidence that effects of the herbal compound preparation
      Shunti-Guduchi are comparable to those of glucosamine for pain (SMD 0.08; 95 % CI
      -0.20, 0.36; P = 0.56) and function (SMD 0.15; 95 % CI -0.12, 0.36; P = 0.41).
      Based on single trials, positive effects were found for the compound preparations
      RA-11, Reosto, and Siriraj Wattana. For Boswellia serrata, Lepidium Sativum, a
      Boswellia serrata containing multicomponent formulation and the compounds
      Nirgundi Taila, Panchatikta Ghrita Guggulu, and Rhumayog, and for non
      pharmacological interventions like Ayurvedic massage, steam therapy, and enema,
      no evidence for significant effects against potential methodological bias was
      found. No severe adverse events were observed in all trials. The drugs Rumalaya
      and Shunti-Guduchi seem to be safe and effective drugs for treatment of OA
      patients, based on these data. However, several limitations relate to clinical
      research on Ayurveda. Well-planned, well-conducted and well-published trials are
      warranted to improve the evidence for Ayurvedic interventions.

PMID- 25062982
TI  - WBGT index revisited after 60 years of use.
AB  - The Wet Bulb Globe Temperature (WBGT) seems to be still used world widely for the
      evaluation of heat stress conditions and it is recommended by ISO and American
      Conference of Governmental Industrial Hygienists as a screening method.
      Unfortunately, many occupational health practitioners and users appear to be
      unaware of its limitations. As the ISO 7243 Standard, based on WBGT, is presently
      under revision, it is an appropriate time to review the validity and
      applicability of this empirical approach to evaluate heat stress. This article
      underlines the main issues about the WBGT index from a rational perspective. 

PMID- 25062983
TI  - Blurring the line between the DNA damage response and transcription: the
      importance of chromatin dynamics.
AB  - DNA damage interferes with the progression of transcription machineries. A tight
      coordination of transcription with signaling and repair of DNA damage is thus
      critical for safeguarding genome function. This coordination involves modulations
      of chromatin organization. Here, we focus on the central role of chromatin
      dynamics, in conjunction with DNA Damage Response (DDR) factors, in controlling
      transcription inhibition and restart at sites of DNA damage in mammalian cells.
      Recent work has identified chromatin modifiers and histone chaperones as key
      regulators of transcriptional activity in damaged chromatin regions. Conversely,
      the transcriptional state of chromatin before DNA damage influences both DNA
      damage signaling and repair. We discuss the importance of chromatin plasticity in
      coordinating the interplay between the DDR and transcription, with major
      implications for cell fate maintenance. 

PMID- 25062984
TI  - Steroid receptors and their ligands: effects on male gamete functions.
AB  - In recent years a new picture of human sperm biology is emerging. It is now
      widely recognized that sperm contain nuclear encoded mRNA, mitochondrial encoded
      RNA and different transcription factors including steroid receptors, while in the
      past sperm were considered incapable of transcription and translation. One of the
      main targets of steroid hormones and their receptors is reproductive function.
      Expression studies on Progesterone Receptor, estrogen receptor, androgen receptor
      and their specific ligands, demonstrate the presence of these systems in mature
      spermatozoa as surface but also as nuclear conventional receptors, suggesting
      that both systemic and local steroid hormones, through sperm receptors, may
      influence male reproduction. However, the relationship between the signaling
      events modulated by steroid hormones and sperm fertilization potential as well as
      the possible involvement of the specific receptors are still controversial
      issues. The main line of this review highlights the current research in human
      sperm biology examining new molecular systems of response to the hormones as well
      as specific regulatory pathways controlling sperm cell fate and biological
      functions. Most significant studies regarding the identification of steroid
      receptors are reported and the mechanistic insights relative to signaling
      pathways, together with the change in sperm metabolism energy influenced by
      steroid hormones are discussed.The reviewed evidences suggest important effects
      of Progesterone, Estrogen and Testosterone and their receptors on spermatozoa and
      implicate the involvement of both systemic and local steroid action in the
      regulation of male fertility potential. 

PMID- 25062985
TI  - Ubiquitin at work: the ubiquitous regulation of the damage recognition step of
      NER.
AB  - Nucleotide excision repair (NER) removes a wide variety of helix distorting DNA
      lesions. NER comprises two damage recognition sub-pathways: GG-NER operates
      genome wide, whereas TC-NER specifically removes transcription-blocking lesions
      from the transcribed strand of actively transcribed genes. NER is a multistep
      process, which requires the concerted action of 30 proteins that need to be
      tightly controlled at the right time and place for efficient repair. Post
      translational protein modifications (PTMs) are common regulators of complex
      protein networks. Several NER factors were shown to be modified by ubiquitin,
      whereas others are actively involved in the ubiquitin-proteasome system itself.
      PTMs by ubiquitylation can be swiftly induced in a reversible manner and have the
      ability to regulate protein function, localization or stability. This makes the
      regulation by ubiquitin highly suitable for the coordination of the complex NER
      reaction. Accumulating evidence, including proteome wide quantitative proteomics
      approaches, showed that especially NER factors involved in the damage recognition
      are regulated by ubiquitin, emphasizing the high level of regulation during the
      initiation of the NER reaction. In this review we will therefore focus on the
      different functions of ubiquitylation during the DNA damage recognition steps of
      NER. 

PMID- 25062986
TI  - Optimization of agitation speed in spinner flask for microcarrier structural
      integrity and expansion of induced pluripotent stem cells.
AB  - In recent times, the study and use of induced pluripotent stem cells (iPSC) have
      become important in order to avoid the ethical issues surrounding the use of
      embryonic stem cells. Therapeutic, industrial and research based use of iPSC
      requires large quantities of cells generated in vitro. Mammalian cells, including
      pluripotent stem cells, have been expanded using 3D culture, however current
      limitations have not been overcome to allow a uniform, optimized platform for
      dynamic culture of pluripotent stem cells to be achieved. In the current work, we
      have expanded mouse iPSC in a spinner flask using Cytodex 3 microcarriers. We
      have looked at the effect of agitation on the microcarrier survival and optimized
      an agitation speed that supports bead suspension and iPS cell expansion without
      any bead breakage. Under the optimized conditions, the mouse iPSC were able to
      maintain their growth, pluripotency and differentiation capability. We
      demonstrate that microcarrier survival and iPS cell expansion in a spinner flask
      are reliant on a very narrow range of spin rates, highlighting the need for
      precise control of such set ups and the need for improved design of more robust
      systems. 

PMID- 25062987
TI  - Cytoprotective propensity of Bacopa monniera against hydrogen peroxide induced
      oxidative damage in neuronal and lung epithelial cells.
AB  - Hydrogen peroxide (H2O2), a major reactive oxygen species (ROS) produced during
      oxidative stress, is toxic to the cells. Hence, H2O2 has been extensively used to
      study the effects of antioxidant and cytoprotective role of phytochemicals. In
      the present investigation H2O2 was used to induce oxidative stress via ROS
      production within PC12 and L132 cells. Cytoprotective propensity of Bacopa
      monniera extract (BME) was confirmed by cell viability assays, ROS estimation,
      lipid peroxidation, mitochondria membrane potential assay, comet assay followed
      by gene expression studies of antioxidant enzymes in PC12 and L132 cells treated
      with H2O2 for 24 h with or without BME pre-treatment. Our results elucidate that
      BME possesses radical scavenging activity by scavenging 2,2-diphenyl-1
      picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid),
      superoxide radical, and nitric oxide radicals. The IC50 value of BME against
      these radicals was found to be 226.19, 15.17, 30.07, and 34.55 ug/ml,
      respectively). The IC50 of BME against ROS, lipid peroxidation and protein
      carbonylation was found to be 1296.53, 753.22, and 589.04 ug/ml in brain and
      1137.08, 1079.65, and 11101.25 ug/ml in lung tissues, respectively. Further
      cytoprotective potency of the BME ameliorated the mitochondrial and plasma
      membrane damage induced by H2O2 as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) and lactate dehydrogenase leakage assays in
      both PC12 and L132 cells. H2O2 induced cellular, nuclear and mitochondrial
      membrane damage was restored by BME pre-treatment. H2O2 induced depleted
      antioxidant status was also replenished by BME pre-treatment. This was confirmed
      by spectrophotometric analysis, semi-quantitative RT-PCR and western blot
      studies. These results justify the traditional usage of BME based on its
      promising antioxidant and cytoprotective property. 

PMID- 25062988
TI  - Non-motor symptoms in Chinese Parkinson's disease patients with and without LRRK2
      G2385R and R1628P variants.
AB  - Non-motor symptoms (NMS) are common among patients with Parkinson's disease (PD).
      However, reports on NMS in Chinese PD population are scarce. Little is known
      about NMS in patients with Asian specific leucine-rich repeat kinase 2 (LRRK2)
      variants in G2385R and R1628P. This study aimed to elucidate the clinical
      characteristics of NMS in Chinese PD patients and to ascertain if there were
      differences in NMS between PD patients with and without LRRK2 variants. A
      multicenter, observational study was conducted with 1,225 sporadic PD (sPD)
      patients recruited from a PD cohort of the Chinese National Consortium on
      neurodegenerative diseases, 163 participants had the LRRK2 variants. The Non
      motor Symptom Questionnaire (NMSQ) was used to screen for the presence of NMS.
      This study found the majority of sPD patients (97.6 %) had at least one NMS. A
      mean of 8.72 NMS (SD = 5.43) was reported per patient. Forgetfulness,
      constipation and daytime sleepiness were found to be the most frequent NMS.
      Moreover, the number of NMS was positively correlated with the age, disease
      duration, Hoehn & Yahr stage and the motor scores of the unified Parkinson's
      disease rating scale. Although no discrepancy was found in the number of NMS
      between sPD patients with and without LRRK2 variants, nocturia was less common in
      LRRK2 variants carriers than in non-carriers (P = 0.045). NMS appear to be
      prevalent in Chinese sPD population. There are no differences in the NMS
      phenotype between LRRK2 and no LRRK2 patients. 

PMID- 25062989
TI  - Effects of dietary Crotalaria pallida seeds on the health and performance of
      laying hens and evaluation of residues in eggs.
AB  - The effect of three dietary concentrations of Crotalaria pallida (C. pallida)
      seeds (0, 1, 2, and 3% w/w) of their normal diet were investigated in commercial
      laying hens during a 35 day feeding trial. All concentrations of C. pallida
      decreased body weight and feed intake (P < 0.05). Egg mass production and average
      egg weight were decreased by feeding of >= 2% C. pallida seeds (P < 0.05). All
      concentrations of C. pallida increased relative lung weight and serum activity of
      ALT, AST and LDH (P < 0.05); 3% C. pallida seeds decreased liver weight (P <
      0.05). Analysis of the C. pallida seeds for dehydropyrrolizidine alkaloid content
      detected usaramine and its N-oxide at a total alkaloid concentration of 0.18%
      (dry weight). Usaramine was also detected in the eggs of all hens fed C. pallida
      seeds.

PMID- 25062990
TI  - Zinc alginate-carboxymethyl cashew gum microbeads for prolonged drug release:
      development and optimization.
AB  - Isoxsuprine HCl-loaded microbeads using sodium alginate (SA)-carboxymethyl cashew
      gum (CMCG) polymer-blends were developed through ionotropic-gelation technique
      using ZnSO4 as cross-linker. Effects of polymer-blend ratio and cross-linker
      concentration on drug encapsulation efficiency (DEE) and cumulative drug release
      at 7 h (R7 h) were optimized by 3(2) factorial design. Optimized microbeads were
      of excellent combination of high DEE (79.92+/-2.51%) and suitable sustained drug
      release pattern over a prolonged period of 7 h (58.67+/-2.26%). The microbead
      surface morphology was analyzed by SEM. The physical state of isoxsuprine HCl
      within the optimized microbead matrix was analyzed by FTIR and DSC. In vitro
      isoxsuprine HCl release from alginate-CMCG microbeads in phosphate buffer (pH,
      6.8) showed prolonged sustained drug release and Korsmeyer-Peppas model
      (R2=0.9959-0.9992) over 7 h.

PMID- 25062991
TI  - Optimization of culture medium and modeling of curdlan production from
      Paenibacillus polymyxa by RSM and ANN.
AB  - Paenibacillus polymyxa ATCC 21830 was used for the production of curdlan gum for
      first time. A Box-Behnken experimental design was applied to optimize six
      variables of batch fermentation culture each at three levels. Statistical
      analyses were employed to investigate the direct and interactive effects of
      variables on curdlan production. Optimum cultural conditions were temperature (50
      degrees C), pH (7), fermentation time (96 h), glucose (100 g/L), yeast extract (3
      g/L) and agitation speed (150 rpm). The yield of curdlan production was 6.89 g/L
      at optimum condition medium. Response surface methodology (RSM) and artificial
      neural network (ANN) were used to model cultural conditions of curdlan
      production. The maximum yield of curdlan production were predicted to be 6.68 and
      6.85 g/L by RSM and ANN at optimum condition. The prediction capabilities of RSM
      and ANN were then statistically compared. The results showed that the ANN model
      is much more accurate in prediction as compared to the RSM. The infrared (IR) and
      NMR spectra, the thermogram of DSC and pattern of X-ray diffraction for the
      curdlan of the present study were almost identical to those of the commercial
      curdlan sample. The average molecular weight of the purified curdlan was
      determined to be 170 kDa by gel permeation chromatography.

PMID- 25062992
TI  - Antioxidant activity of exopolysaccharide from probiotic strain Enterococcus
      faecium (BDU7) from Ngari.
AB  - "Ngari" is a traditional fermented fish of Manipur and considered for its
      therapeutic value in healing stomach ulcers. In the present study, an attempt was
      made to isolate and identify an efficient antioxidant probiotic isolate from
      Ngari. BDU7 with potent antioxidant property was isolated and characterized. The
      isolate was identified by 16S rRNA genotyping as Enterococcus faecium. E. faecium
      showed auto aggregation and hydrophobicity of 72.7 and 54.8% respectively. The
      extrapolysaccharide (EPS) was extracted from the culture free supernatant and
      assayed for its radical scavenging activity. The EPS showed significant 2, 2
      diphenyl-1-picrylhydrazyl (DPPH) (63.5%), superoxide (77.3%) and hydroxyl (38.4%)
      radical scavenging ability. The structural analysis of the extracted and purified
      EPS was performed by FTIR and NMR analysis. From the present study E. faecium
      BDU7 can be claimed as a promising and an efficient probiotic candidate. The
      present study evidenced that EPS from E. faecium BDU7 showed strong DPPH and
      superoxide radical scavenging ability in vitro. Considering its potency as a
      potential antioxidant the extracted EPS can find wide application in functional
      food and pharmaceutical formulations. 

PMID- 25062993
TI  - Fluoroalcohols-induced modulation and amyloid formation in conalbumin.
AB  - In this study we are reporting the conformational modulation as well as the
      plausible mechanism of structural perturbation in conalbumin (CA). The overall
      structure of CA is altered by the change in dielectric constant upon addition of
      fluoroalcohols (TFE and HFIP). We studied the formation of aggregates in CA at pH
      7.0 by multiple structural probes in the presence of TFE and HFIP. The protein
      aggregates maximally in 15% (v/v) TFE and 3% (v/v) HFIP. ANS, ThT binding and
      transmission electron microscopy data suggest that the aggregates induced by TFE
      and HFIP have amyloid-like properties. Higher concentrations of TFE and HFIP
      causes increase in helical propensity. Far-UV circular dichroism, intrinsic
      fluorescence, ANS and ThT fluorescence data suggests that formation of a
      partially structured intermediate state precedes the onset of the aggregation
      process. 

PMID- 25062994
TI  - Effects of a flow field on amyloid fibrillogenesis in a beta-lactoglobulin
      solution.
AB  - The effects of a flow field on the amyloid fibrillogenesis of beta-lactoglobulin
      (betaLG) were investigated using a flow birefringence method and AFM imaging
      experiments. A 4 wt% betaLG aqueous solution was incubated at pH 2 and 80 degrees
      C. A flow field was then applied by stirring at 250 and 474 rpm. An incubation
      without stirring was used as a control sample. Flow birefringence measurements
      were taken at room temperature from the incubated sample solutions in which an
      elongational flow field was used. The birefringence pattern obtained indicated
      that the fibrils formed by the incubation were rigid rod-like molecules.
      Birefringence relaxation experiments revealed at least two relaxation processes,
      suggesting a double peaked distribution function for fibrils length. The length
      distribution of fibrils expected from the birefringence experiments was confirmed
      by the AFM images of amyloid fibrils. The order of the expected length of the
      resultant fibrils in both longer and shorter length distributions was those
      stirred at 250 rpm?474 rpm>0 rpm. The effects of the flow field applied during
      the incubation on amyloid fibrillogenesis was discussed on the basis of the rate
      process consideration. The present results demonstrated that the flow field
      should be considered as an important factor that regulates the fibrillogenesis of
      globular proteins.

PMID- 25062995
TI  - Locally applied macrophage-activating lipopeptide-2 (MALP-2) promotes early
      vascularization of implanted porous polyethylene (Medpor(r)).
AB  - Porous polyethylene (Medpor(r)) is frequently used in craniofacial reconstructive
      surgery. Rapid vascularization of the biomaterial crucially contributes to its
      adequate incorporation without complications. Macrophage-activating lipopeptide-2
      (MALP-2) is a toll-like receptor (TLR)-2/6 agonist with pro-angiogenic
      properties. Herein we analyzed whether local single-shot application of MALP-2
      improves the angiogenic host tissue response to Medpor(r). Medpor(r) (3 mm*3
      mm*0.25 mm) was implanted into dorsal skinfold chambers of BALB/c mice topically
      exposed to different MALP-2 doses (0.1 and 0.5 MUg) or vehicle (control). The
      vascularization of the implants and the inflammatory foreign body reaction was
      analyzed using intravital fluorescence microscopy, histology and
      immunohistochemistry over 14 days. MALP-2 treatment dose-dependently improved the
      vascularization of Medpor(r), as indicated by a significantly higher functional
      microvessel density at the border and center of the implants when compared to
      controls. This was associated with a temporary increase of adherent leukocytes in
      host tissue venules during the first 3 days after implantation. At day 14,
      implants in MALP-2-treated chambers were surrounded by granulation tissue, which
      exhibited a significantly higher density of CD31-positive microvessels and number
      of F4/80-positive macrophages when compared to controls. Additional biomaterial
      free chambers did not show any signs of angiogenesis when treated with MALP-2.
      This indicates that locally applied MALP-2 effectively stimulates the early
      vascularization of Medpor(r) without inducing any local or systemic side effects.
      Accordingly, this easy approach may further improve the rapid incorporation of
      this biomaterial at the implantation site.

PMID- 25062996
TI  - Improved maternal health since the ICPD: 20 years of progress.
AB  - BACKGROUND: The 1994 Conference on Population and Development (ICPD) was a
      turning point in the field of sexual and reproductive health--repositioning
      population and development programs globally in the context of reproductive
      rights, gender equity, and women's empowerment. PROGRESS SINCE ICPD: ICPD
      solidified the importance of women's health and safe motherhood alongside other
      health and development priorities while laying the groundwork for the Millennium
      Development Goals. CHALLENGES: Some goals envisioned by ICPD have been met.
      Others still need to be addressed. Global declines in maternal mortality are
      indicative of success, although improving measurement, quality of care and access
      to services, while addressing the social determinants that influence maternal
      health remain priorities. RECOMMENDATIONS: Renewed political will to address the
      remaining challenges is necessary for the post-2015 development agenda so that
      women's health throughout the world continues to be supported with ambitious, yet
      feasible goals that take into account the world's evolving development
      priorities.

PMID- 25062997
TI  - Short interpregnancy interval associated with preterm birth in U S adolescents.
AB  - A short interpregnancy interval (IPI) is a risk factor for preterm delivery among
      women of reproductive age. As limited data exist concerning adolescents, we aimed
      to examine the association between short IPIs and preterm birth among adolescents
      using a majority of US births. Using 2007-2008 US natality data, we assessed the
      relationship between IPIs <3, 3-5, 6-11, and 12-17 months and moderately (32-36
      weeks) and very (<32 weeks) preterm singleton live births among mothers <20
      years, relative to IPIs 18-23 months. Adjusted odds ratios (aORs) and 95 %
      confidence intervals (95 % CIs) adjusted for maternal race, age, previous preterm
      deliveries, marital status, smoking and prenatal care were determined from a
      multivariable multinomial logistic regression model. In 2007-2008, there were
      85,077 singleton live births to women aged <20 who had one previous live birth,
      69 % of which followed IPIs <=18 months. Compared with IPIs 18-23 months, short
      IPIs were associated with moderately preterm birth for IPIs <3 months (aOR 1.89,
      95 % CI 1.70-2.10), 3-5 months (aOR 1.33, 95 % CI 1.22-1.47), and 6-12 months
      (aOR 1.11, 95 % CI 1.02-1.21). IPIs <3 and <6 months were also associated with
      very preterm birth, with aORs of 2.52 (95 % CI 1.98-3.22) and 1.68 (95 % CI 1.35
      2.10) respectively. Many adolescent mothers with repeat births have short IPIs,
      and shorter IPIs are associated with preterm birth in a dose-dependent fashion.
      Increasing adolescent mothers' use of effective contraception postpartum can
      address both unintended adolescent births and preterm birth. 

PMID- 25062999
TI  - Cystic fibrosis transmembrane conductance regulator protein (CFTR) expression in
      the developing human brain: comparative immunohistochemical study between
      patients with normal and mutated CFTR.
AB  - Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein has recently
      been shown to be expressed in the human adult central nervous system (CNS). As
      CFTR expression has also been documented during embryonic development in several
      organs, such as the respiratory tract, the intestine and the male reproductive
      system, suggesting a possible role during development we decided to investigate
      the expression of CFTR in the human developing CNS. In addition, as some,
      although rare, neurological symptoms have been reported in patients with CF, we
      compared the expression of normal and mutated CFTR at several fetal stages.
      Immunohistochemistry was performed on brain and spinal cord samples of foetuses
      between 13 and 40 weeks of gestation and compared with five patients with cystic
      fibrosis (CF) of similar ages. We showed in this study that CFTR is only
      expressed in neurons and has an early and widespread distribution during
      development. Although we did not observe any cerebral abnormality in patients
      with CF, we observed a slight delay in the maturation of several brain
      structures. We also observed different expression and localization of CFTR
      depending on the brain structure or the cell maturation stage. Our findings,
      along with a literature review on the neurological phenotypes of patients with
      CF, suggest that this gene may play previously unsuspected roles in neuronal
      maturation or function. 

PMID- 25063000
TI  - Comparative analysis of H&E and Prussian blue staining in a mouse model of
      cerebral microbleeds.
AB  - Cerebral microbleeds are microscopic hemorrhages with deposits of blood products
      in the brain, which can be visualized with MRI and are implicated in
      cerebrovascular diseases. Hematoxylin and eosin (H&E) and Perl's Prussian blue
      are popular staining methods used to localize cerebral microbleeds in pathology.
      This paper compared these two staining techniques in a mouse model of cerebral
      microbleeds. We used lipopolysaccharide (LPS) to induce cerebral
      microhemorrhages. C57B6 mice were treated with LPS (5 mg/kg, i.p.) or vehicle at
      baseline and at 24 hr. The brains were extracted 48 hr after the first injection
      and adjacent coronal sections were stained with H&E and Prussian blue to compare
      the effectiveness of the two staining techniques. H&E-positive stains were
      increased with LPS treatment and were correlated with grossly visible
      microhemorrhages on the brain surface; Prussian blue-positive stains, by
      comparison, showed no significant increase with LPS treatment and did not
      correlate with either H&E-positive stains or surface microhemorrhages. H&E
      staining is thus a more reliable indicator of acute bleeding events induced by
      LPS in this model within a short time span. 

PMID- 25063001
TI  - Endothelial matrix assembly during capillary morphogenesis: insights from
      chimeric TagRFP-fibronectin matrix.
AB  - Biologically relevant, three-dimensional extracellular matrix is an essential
      component of in vitro vasculogenesis models. WI-38 fibroblasts assemble a 3D
      matrix that induces endothelial tubulogenesis, but this model is challenged by
      fibroblast senescence and the inability to distinguish endothelial cell-derived
      matrix from matrix made by WI-38 fibroblasts. Matrices produced by hTERT
      immortalized WI-38 recapitulated those produced by wild type fibroblasts. ECM
      fibrils were heavily populated by tenascin-C, fibronectin, and type VI collagen.
      Nearly half of the total type I collagen, but only a small fraction of the type
      IV collagen, were incorporated into ECM. Stable hTERT-WI-38 transfectants
      expressing TagRFP-fibronectin incorporated TagRFP into ~90% of the fibronectin in
      3D matrices. TagRFP-fibronectin colocalized with tenascin-C and with type I
      collagen in a pattern that was similar to that seen in matrices from wild type WI
      38. Human Umbilical Vein Endothelial Cells (HUVEC) formed 3D adhesions and tubes
      on WI38-hTERT-TagRFP-FN-derived matrices, and the TagRFP-fibronectin component of
      this new 3D human fibroblast matrix model facilitated the demonstration of
      concentrated membrane type 1 metalloprotease and new HUVEC FN and collagen type
      IV fibrils during EC tubulogenesis. These findings indicate that WI-38-hTERT- and
      WI-38-hTERT-TagRFP-FN-derived matrices provide platforms for the definition of
      new matrix assembly and remodeling events during vasculogenesis. 

PMID- 25063002
TI  - Cohort profile update: 2004 Pelotas (Brazil) Birth Cohort Study. Body
      composition, mental health and genetic assessment at the 6 years follow-up.
AB  - This is an update of the 2004 Pelotas Birth Cohort profile, originally published
      in 2011. In view of the high prevalence of overweight and mental health problems
      among Brazilian children, together with the availability of state-of-the-art
      equipment to assess body composition and diagnostic tests for mental health in
      childhood, the main outcomes measured in the fifth follow-up (mean age 6.8 years)
      included child body composition, mental health and cognitive ability. A total of
      3722 (90.2%) of the original mothers/carers were interviewed and their children
      examined in a clinic where they underwent whole-body dual X-ray absorptiometry
      (DXA), air displacement plethysmography and a 3D photonic scan. Saliva samples
      for DNA were obtained. Clinical psychologists applied the Development and Well
      Being Assessment questionnaire and the Wechsler Intelligence Scale for Children
      to all children. Results are being compared with those of the two earlier cohorts
      to assess the health effects of economic growth and full implementation of public
      policies aimed at reducing social inequalities in the past 30 years. For further
      information visit the programme website at [http://www.epidemio
      ufpel.org.br/site/content/coorte_2004/questionarios.php]. Applications to use the
      data should be made by contacting 2004 cohort researchers and filling in the
      application form available at [http://www.epidemio
      ufpel.org.br/site/content/estudos/formularios.php]. 

PMID- 25063003
TI  - Upper body kinematics in patients with cerebellar ataxia.
AB  - Although abnormal oscillations of the trunk are a common clinical feature in
      patients with cerebellar ataxia, the kinematic behaviour of the upper body in
      ataxic patients has yet to be investigated in quantitative studies. In this
      study, an optoelectronic motion analysis system was used to measure the ranges of
      motion (ROMs) of the head and trunk segments in the sagittal, frontal and yaw
      planes in 16 patients with degenerative cerebellar ataxia during gait at self
      selected speed. The data obtained were compared with those collected in a gender
      , age- and gait speed-matched sample of healthy subjects and correlated with gait
      variables (time-distance means and coefficients of variation) and clinical
      variables (disease onset, duration and severity). The results showed
      significantly larger head and/or trunk ROMs in ataxic patients compared with
      controls in all three spatial planes, and significant correlations between trunk
      ROMs and disease duration and severity (in sagittal and frontal planes) and time
      distance parameters (in the yaw plane), and between both head and trunk ROMs and
      swing phase duration variability (in the sagittal plane). Furthermore, the ataxic
      patients showed a flexed posture of both the head and the trunk during walking.
      In conclusion, our study revealed abnormal motor behaviour of the upper body in
      ataxic patients, mainly resulting in a flexed posture and larger oscillations of
      the head and trunk. The results of the correlation analyses suggest that the
      longer and more severe the disease, the larger the upper body oscillations and
      that large trunk oscillations may explain some aspects of gait variability. These
      results suggest the need of specific rehabilitation treatments or the use of
      elastic orthoses that may be particularly useful to reduce trunk oscillations and
      improve dynamic stability. 

PMID- 25063004
TI  - Comparative evaluation of preprocessing freeware on chromatography/mass
      spectrometry data for signature discovery.
AB  - Preprocessing software, which converts large instrumental data sets into a
      manageable format for data analysis, is crucial for the discovery of chemical
      signatures in metabolomics, chemical forensics, and other signature-focused
      disciplines. Here, four freely available and published preprocessing tools known
      as MetAlign, MZmine, SpectConnect, and XCMS were evaluated for impurity profiling
      using nominal mass GC/MS data and accurate mass LC/MS data. Both data sets were
      previously collected from the analysis of replicate samples from multiple stocks
      of a nerve-agent precursor and method blanks. Parameters were optimized for each
      of the four tools for the untargeted detection, matching, and cataloging of
      chromatographic peaks from impurities present in the stock samples. The peak
      table generated by each preprocessing tool was analyzed to determine the number
      of impurity components detected in all replicate samples per stock and absent in
      the method blanks. A cumulative set of impurity components was then generated
      using all available peak tables and used as a reference to calculate the percent
      of component detections for each tool, in which 100% indicated the detection of
      every known component present in a stock. For the nominal mass GC/MS data,
      MetAlign had the most component detections followed by MZmine, SpectConnect, and
      XCMS with detection percentages of 83, 60, 47, and 41%, respectively. For the
      accurate mass LC/MS data, the order was MetAlign, XCMS, and MZmine with detection
      percentages of 80, 45, and 35%, respectively. SpectConnect did not function for
      the accurate mass LC/MS data. Larger detection percentages were obtained by
      combining the top performer with at least one of the other tools such as 96% by
      combining MetAlign with MZmine for the GC/MS data and 93% by combining MetAlign
      with XCMS for the LC/MS data. In terms of quantitative performance, the reported
      peak intensities from each tool had averaged absolute biases (relative to peak
      intensities obtained using instrument software) of 41, 4.4, 1.3 and 1.3% for
      SpectConnect, MetAlign, XCMS, and MZmine, respectively, for the GC/MS data. For
      the LC/MS data, the averaged absolute biases were 22, 4.5, and 3.1% for MetAlign,
      MZmine, and XCMS, respectively. In summary, MetAlign performed the best in terms
      of the number of component detections; however, more than one preprocessing tool
      should be considered to avoid missing impurities or other trace components as
      potential chemical signatures. 

PMID- 25063005
TI  - Can mild bilateral sensorineural hearing loss affect developmental abilities in
      younger school-age children?
AB  - The research study was conducted for the purpose of examining the influence of
      mild bilateral sensorineural hearing loss (MBSNHL) on developmental abilities of
      younger school-age children. The sample encompassed 144 children with MBSNHL,
      aged 7.5-11 (M = 8.85). MBSNHL (20-40 dB HL) was identified by pure tone
      audiometry. The control group encompassed 160 children with normal hearing. The
      Acadia test of developmental abilities was used for assessment of developmental
      abilities. Although statistically significant differences between participants
      with MBSNHL and those with normal hearing were established in the majority of
      estimated developmental abilities domains, those differences do not indicate any
      significant delay in development of assessed abilities, except in the domain of
      auditory discrimination. The obtained results call for a systematic approach to
      children with MBSNHL in elementary schools. 

PMID- 25063006
TI  - Partial breast reconstruction for the medial quadrants using the omental flap.
AB  - BACKGROUND: The indications for breast-conserving surgery have increased due to
      the establishment of various volume-replacement techniques. We have used the
      omental flap for partial breast reconstruction. Unlike other autologous flaps,
      the medial quadrants represent a suitable field for the omental flap. We report a
      technique for partial breast reconstruction using the omental flap. METHODS: For
      tumors in the lower medial quadrant, wide excision was performed through an
      inframammary skin incision. The omental flap was harvested laparoscopically, and
      a subcutaneous tunnel was created towards the xyphoid process. The omental flap
      was extracted through the tunnel and used to fill the defect directly. For tumors
      in the upper medial quadrant, a periareolar incision was usually used for wide
      excision, and an additional small inframammary incision was made to extract the
      omental flap. The pedicle of the flap was made as slim as possible by defatting,
      and the subcutaneous fat tissue around the tunnel was excised to avoid bulging
      caused by the subcutaneous tunnel. RESULTS: A total of 51 patients with tumors in
      the medial quadrants underwent partial breast reconstruction with the omental
      flap between April 2002 and July 2013. The surgical margin was positive in two
      patients, and there was only one case of local recurrence. The complication rate
      was 7.8 %, and all of them were minor. Cosmetic results were mostly satisfactory
      with minimal donor-site scars. CONCLUSIONS: The omental flap is an attractive
      volume replacement technique for difficult quadrants of the breast with minimal
      donor-site morbidities and deformities.

PMID- 25063007
TI  - Embracing national cancer registries for improved care of rare tumors.

PMID- 25063008
TI  - Treatment of clinical T2N0M0 esophageal cancer.

PMID- 25062998
TI  - Mast cell function: a new vision of an old cell.
AB  - Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed
      as effectors of allergy. It has been only in the past two decades that mast cells
      have gained recognition for their involvement in other physiological and
      pathological processes. Mast cells have a widespread distribution and are found
      predominantly at the interface between the host and the external environment.
      Mast cell maturation, phenotype and function are a direct consequence of the
      local microenvironment and have a marked influence on their ability to
      specifically recognize and respond to various stimuli through the release of an
      array of biologically active mediators. These features enable mast cells to act
      as both first responders in harmful situations as well as to respond to changes
      in their environment by communicating with a variety of other cells implicated in
      physiological and immunological responses. Therefore, the critical role of mast
      cells in both innate and adaptive immunity, including immune tolerance, has
      gained increased prominence. Conversely, mast cell dysfunction has pointed to
      these cells as the main offenders in several chronic allergic/inflammatory
      disorders, cancer and autoimmune diseases. This review summarizes the current
      knowledge of mast cell function in both normal and pathological conditions with
      regards to their regulation, phenotype and role. 

PMID- 25063009
TI  - The utility of sentinel lymph node biopsy in patients with ductal carcinoma in
      situ suspicious for microinvasion on core biopsy.
AB  - BACKGROUND: When microinvasion cannot be ruled out on core needle biopsy (CNB) in
      the setting of ductal carcinoma in situ (DCIS), the surgeon must decide whether
      to perform a sentinel lymph node biopsy (SLNB) at the time of surgery. Up to 10 %
      of patients with T1mi have nodal disease, but the utility of SLNB in DCIS
      suspicious for microinvasion (Smic) is unclear. METHODS: The University of
      Chicago pathology database was queried for a diagnosis of Smic or definite
      microinvasion (Mic) on CNB from 2000 to 2014. We analyzed histology, imaging,
      core needle size, and the use of myoepithelial immunohistochemistry (IHC)
      markers. RESULTS: We identified 103 women, 72 with Smic and 31 with Mic on CNB.
      After surgery, 32 % of Smic patients had infiltrating ductal carcinoma (IDC).
      Seventy-two percent of Smic patients underwent SLNB, with 67 % performed at the
      initial surgery. SLNB was positive in 6 % and 10 % of Smic and Mic patients,
      respectively (p = 0.66). Excluding N1mic, the incidence of macrometastatic nodal
      disease was 1.9 % for Smic patients and 3.3 % for Mic patients (p = 1.00). For
      Smic patients, IDC was associated with a larger lesion size and smaller CNB
      needle. In the setting of Smic, grade, necrosis, or presence of a mass did not
      increase the risk of IDC. CONCLUSIONS: In patients with Smic on CNB, the
      incidence of macrometastatic nodal disease after SLNB is rare. Surgeons may
      consider omitting SLNB until IDC is definitively confirmed, especially in
      patients with Smic apart from other high-risk features.

PMID- 25063010
TI  - The influence of sentinel lymph node biopsy on survival for intermediate
      thickness melanoma.
AB  - BACKGROUND: The Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) failed to
      demonstrate a survival advantage for sentinel lymph node biopsy (SNB) in
      melanoma. This may have been secondary to inadequate statistical power. This
      study was designed to determine the impact of SNB on melanoma-specific survival
      (MSS) in a larger patient cohort. METHODS: From 2003-2008, patients with tumors 1
      4 mm in thickness and clinically negative nodes were identified within the SEER
      registry. Propensity score was used to create two matched cohorts: those who
      underwent a wide excision with SNB or wide excision alone. RESULT: A total of
      15,274 met inclusion criteria and 7,910 comprised the match cohort. Average age
      was 67.4 years. The majority were male (62.3 %) and white (97.2 %). Primary
      tumors were most frequently nonulcerated (77.1 %), located on the extremity (42.3
      %), and T2 (64.1 %). There were 3,955 patients in both the SNB and observation
      groups. There was no significant difference in gender, ethnicity, ulceration
      status, primary site, or T-classification between the groups. Improved 5-year MSS
      was associated with SNB (85.7 vs. 84.0 %), female gender (88.3 vs. 82.7 %),
      absence of ulceration (87.5 vs. 75.7 %), extremity location (87.4 %), T2 disease
      (88.6 vs. 77.9 %), and a negative SNB (88.9 vs. 64.8 %). The relationships
      between observation [hazard ratio (HR) 1.18], male gender (HR 1.33), ulceration
      (HR 1.77), head-and-neck location (HR 1.34), and T3 disease (HR 1.82) persisted
      on multivariate analysis. CONCLUSIONS: Status of the sentinel node is the
      strongest predictor of survival in patients with intermediate thickness melanoma.
      SNB compared with observation was associated with a modest survival advantage.

PMID- 25063011
TI  - The Early Mobility Bundle: a simple enhancement of therapy which may reduce
      incidence of hospital-acquired pneumonia and length of hospital stay.
AB  - BACKGROUND: Early mobility facilitated by physiotherapy has been shown to reduce
      the incidence of hospital-acquired pneumonia (HAP) in patients with hip fractures
      but its effect on HAP incidence in medical patients has not yet been studied.
      AIM: To determine whether early mobility aided by physiotherapy reduces the
      incidence of HAP and length of stay in patients on medical wards. METHODS: One
      respiratory and one elderly care medicine ward in one hospital association in
      Birmingham, UK, received the 'Early Mobility Bundle'. The bundle consisted of
      extra targeted physiotherapy and collaboration with ward staff to encourage and
      promote activity. The incidence of HAP, falls, pressure sores, length of stay
      (LOS) and activity level were then compared to two matched wards within the same
      hospital association. RESULTS: HAP incidence was significantly lower in the
      intervention group (P < 0.0001) and remained so after adjusting for confounders
      (P = 0.001). Activity levels were higher (P = 0.04) and patients' LOS was more
      likely to fall in the lowest quartile (OR: 1.44; P = 0.009) in the intervention
      group. There was no significant difference in other outcomes. CONCLUSION: The
      Early Mobility Bundle demonstrates a promising method to reduce the incidence of
      HAP and to increase activity in medical inpatients.

PMID- 25063012
TI  - Thirteen years of surgical site infection surveillance in Swiss hospitals.
AB  - BACKGROUND: Surveillance is an essential element of surgical site infection (SSI)
      prevention. Few studies have evaluated the long-term effect of these programmes.
      AIM: To present data from a 13-year multicentre SSI surveillance programme from
      western and southern Switzerland. METHODS: Surveillance with post-discharge
      follow-up was performed according to the US National Nosocomial Infections
      Surveillance (NNIS) system methods. SSI rates were calculated for each surveyed
      type of surgery, overall and by year of participation in the programme. Risk
      factors for SSI and the effect of surveillance time on SSI rates were analysed by
      multiple logistic regression. FINDINGS: Overall SSI rates were 18.2% after 7411
      colectomies, 6.4% after 6383 appendicectomies, 2.3% after 7411 cholecystectomies,
      1.7% after 9933 herniorrhaphies, 1.6% after 6341 hip arthroplasties, and 1.3%
      after 3667 knee arthroplasties. The frequency of SSI detected after discharge
      varied between 21% for colectomy and 94% for knee arthroplasty. Independent risk
      factors for SSI differed between operations. The NNIS risk index was predictive
      of SSI in gastrointestinal surgery only. Laparoscopic technique was protective
      overall, but associated with higher rates of organ-space infections after
      appendicectomy. The duration of participation in the surveillance programme was
      not associated with a decreased SSI rate for any of the included procedure.
      CONCLUSION: These data confirm the effect of post-discharge surveillance on SSI
      rates and the protective effect of laparoscopy. There is a need to establish
      alternative case-mix adjustment methods. In contrast to other European
      programmes, no positive impact of surveillance duration on SSI rates was
      observed.

PMID- 25063014
TI  - Facilitators and barriers around teaching concepts of hand hygiene to
      undergraduate medical students.
AB  - BACKGROUND: Currently, there is limited literature examining the impact and
      appropriateness of the educational approaches used to teach medical students
      concepts around hand hygiene (HH). AIM: To explore: (i) the perspectives of key
      academics and medical students towards HH and factors influencing compliance;
      (ii) the current teaching practices around HH in the medical school. We also
      aimed to examine options for new teaching and learning approaches to help improve
      student knowledge and attitudes towards HH. METHODS: Individual, in-depth
      interviews were conducted with key academics and medical students. Transcripts
      were analysed thematically. FINDINGS: Participants felt that students do not
      value the teaching around HH, nor do they find it interesting, especially in
      comparison to other subjects taught in the medical programme. The use of
      professional modelling, assessment tasks and feedback from patients and
      colleagues were the major educational recommendations; these could be implemented
      to help improve the attitudes of medical students towards HH and hopefully their
      compliance. Regular, small, group-scenario-based and/or practical hands-on
      sessions were also proposed. The need for a culture change was the overarching
      theme to foster sustainable HH practices among medical students. CONCLUSION:
      Assessment and scenario-based learning and teaching approaches should be
      considered to help improve HH behaviours among medical students. Sustainability
      of these practices is likely to require role models and culture change around
      infection control.

PMID- 25063013
TI  - Ethanol versus heparin locks for the prevention of central venous catheter
      associated bloodstream infections: a randomized trial in adult haematology
      patients with Hickman devices.
AB  - The effectiveness of ethanol locks for prevention of central venous catheter
      (CVC)-associated bloodstream infection (CLABSI) in adult haematology patients has
      not been thoroughly evaluated. This study aimed to compare prospectively
      heparinized saline with 70% ethanol locks using 2 h dwell time in patients with
      tunnelled CVCs. In saline (N = 43) and ethanol (N = 42) groups, CLABSI rates were
      6.0 [95% confidence interval (CI): 3.4-9.8] and 4.1 (95% CI: 1.9-7.7) per 1000
      CVC days, respectively (P = 0.42). In the ethanol group, two exit-site infections
      and one tunnel/pocket infection were observed. Reduction in device-associated
      infection was not achieved with prophylactic 70% ethanol locks in patients with
      haematological malignancy and tunnelled CVCs.

PMID- 25063015
TI  - Complete remission of plantar fasciitis with a gluten-free diet: relationship or
      just coincidence?
AB  - We report the case of a 46-year-old woman with no known history for gluten
      sensitivity who presented severe heel pain, and was successfully managed with a
      gluten-free diet. Previously she had been unsuccessfully treated with several
      conservative remedies. The presence of musculoskeletal problems in patients with
      gluten sensitivity is not rare. To the best of our knowledge, however, this is
      the first case report mentioning the successful management of plantar fasciitis
      with a gluten-free diet. The case report highlights the importance of considering
      gluten sensitivity among other possible differential diagnosis for
      musculoskeletal pain insensitive to traditional therapies. 

PMID- 25063016
TI  - Complete medial column dislocation at the cuneonavicular joint: an unusual
      Lisfranc-like injury.
AB  - Lisfranc injuries represent a wide spectrum of different injuries at the
      tarsometatarsal joint. Not all types fit the currently available classifications.
      This case illustrates a rare subtype of a Lisfranc injury, with a dislocation of
      the entire first ray. It is presented to create more awareness for midfoot
      injuries. This article reviews the literature and provides recommendations for
      the treatment of similar cases in the future. 

PMID- 25063017
TI  - Hyaluronidase alters the lipid profile of cumulus cells as detected by MALDI-TOF
      MS and multivariate analysis.
AB  - This research aimed to study the changes in lipid composition in cumulus cells
      using hyaluronidase according to the intracytoplasmic sperm injection protocol
      commonly used in human reproduction clinics. The lipid extraction was performed
      by the Blight-Dyer protocol and the lipid profiles were obtained by MALDI-TOF MS
      in positive and negative modes. The mass spectra data were processed with
      MassLynx and the statistical analysis was performed using MetaboAnalyst 2.0.
      Fifteen ions were selected for each mode as potential markers for differences
      between the groups. These ions were identified in the human metabolome database
      as phosphatidylserine with and without treatment, phosphatidylethanolamine in the
      after treatment group and phosphatidylinositol in the before treatment group,
      which are lipids that may be involved in cell apoptosis and signaling. We
      concluded that MALDI-TOF MS coupled with multivariate analysis can be utilized as
      a strategy to obtain and study the lipid profiles of cumulus cells and as a tool
      to study the metabolic state of cumulus cells. 

PMID- 25063018
TI  - Test of the depression distress amplification model in young adults with elevated
      risk of current suicidality.
AB  - Suicide is a leading cause of death among young adults and the rate of suicide
      has been increasing for decades. A depression distress amplification model posits
      that young adults with comorbid depression and anxiety have elevated suicide
      rates due to the intensification of their depressive symptoms by anxiety
      sensitivity cognitive concerns. The current study tested the effects of anxiety
      sensitivity subfactors as well as the depression distress amplification model in
      a very large sample of college students with elevated suicide risk. Participants
      were 721 college students who were at elevated risk of suicidality (scored>0 on
      the Beck Scale for Suicide Ideation). Consistent with prior work, anxiety
      sensitivity cognitive concerns, but not physical or social concerns, were
      associated with suicidal ideation. Consistent with the depression distress
      amplification model, in individuals high in depression, anxiety sensitivity
      cognitive concerns predicted elevated suicidal ideation but not among those with
      low depression. The results of this study corroborate the role of anxiety
      sensitivity cognitive concerns and the depression distress amplification model in
      suicidal ideation among a large potentially high-risk group of college students.
      The depression distress amplification model suggests a specific mechanism,
      anxiety sensitivity cognitive concerns, that may be responsible for increased
      suicide rates among those with comorbid anxiety and depression. 

PMID- 25063020
TI  - Cryptococcosis in kidney transplant recipients in a Chinese university hospital
      and a review of published cases.
AB  - BACKGROUND: Cryptococcosis is a severe fungal infection with a high mortality
      rate among solid-organ transplant recipients. Today, China is among the countries
      performing the most kidney transplants worldwide, however data on the association
      of cryptococcosis with kidney transplantation in mainland China remain scarce and
      fragmented. METHODS: We retrospectively analyzed cases of culture-confirmed
      cryptococcosis following kidney transplantation that have occurred at our
      hospital and reviewed the published cases in China over the last 30 years.
      RESULTS: Cryptococcosis in kidney transplant recipients was mainly caused by
      Cryptococcus neoformans var. grubii VNI strains and occurred most frequently in
      patients aged 41-50 years (37.9%, 11/29). The average time to infection after
      kidney transplantation was 5.16 +/- 3.97 years. The clinical manifestations were
      found to be diverse, with slight to moderate headache and fever, meningeal
      irritation, and high cerebrospinal fluid pressure being relatively common.
      Physicians should be alert to these symptoms among kidney transplant recipients.
      CONCLUSIONS: Cryptococcosis is a serious infection among kidney transplant
      recipients in mainland China. It has unique characteristics, such as a relatively
      long time to onset after kidney transplantation, and diverse clinical
      manifestations. Treatment with intrathecal injection of amphotericin B is
      considered effective for central nervous system involvement. The findings of this
      study also highlight the urgent need for multicenter, prospective, and
      multidisciplinary clinical studies and education on cryptococcosis in kidney
      transplant recipients in China.

PMID- 25063019
TI  - Family history of psychosis as a predictor or protective factor of social
      maladjustment in a population at clinical high risk for psychosis.
AB  - Literature suggests that social maladjustment is predictive of psychosis. We
      assessed 70 clinical high risk (CHR) patients for social maladjustment. There
      were no significant differences between patients with a positive or negative
      family history, suggesting that the relationship between social maladjustment and
      psychosis found in the recent literature may not translate to a relationship
      between social maladjustment and family history of psychosis in a CHR population.

PMID- 25063021
TI  - Outbreak of Kyasanur Forest disease in Thirthahalli, Karnataka, India, 2014.
AB  - Kyasanur Forest disease virus (KFDV) was first identified in 1957, when it was
      isolated from a sick monkey from the Kyasanur Forest in Karnataka State, India.
      Since then it has been reported to be enzootic in five districts of Karnataka
      State, India. Recent reports of human infections have reached an alarming level,
      in spite of the availability of a vaccine. This disease has also been reported
      from new areas, such as Tamil Nadu and Kerala State. During January-March 2014,
      KFDV-positive cases were detected in Thirthahalli taluk, Shimoga District,
      Karnataka State, India. Here, we report an outbreak of Kyasanur Forest disease
      occurring in the Kannangi and Konandur area, Thirthahalli taluk in Karnataka
      State, India, with sporadic cases from eight other areas. 

PMID- 25063022
TI  - Retrospective search for dengue vector mosquito Aedes albopictus in areas visited
      by a German traveler who contracted dengue in Japan.
AB  - A German traveler developed dengue fever in late August 2013, following a direct
      flight from Germany. Autochthonous dengue virus (DENV) infection has not been
      reported in Japan. To evaluate the risk of autochthonous DENV transmission in
      Japan, the authors performed a retrospective search of the five areas visited by
      the German patient to determine the population density of dengue vector mosquito,
      Aedes albopictus. The annual mean temperature of each area was higher than 12
      degrees C, which is considered suitable for the establishment of A. albopictus
      populations. Our retrospective search revealed the population density of A.
      albopictus to be high in the urban areas of Japan. 

PMID- 25063024
TI  - Historical perspectives of The American Association for Thoracic Surgery: Claude
      S. Beck (1894-1971).

PMID- 25063023
TI  - Phytochrome regulation of plant immunity in vegetation canopies.
AB  - Plant immunity against pathogens and herbivores is a central determinant of plant
      fitness in nature and crop yield in agroecosystems. Plant immune responses are
      orchestrated by two key hormones: jasmonic acid (JA) and salicylic acid (SA).
      Recent work has demonstrated that for plants of shade-intolerant species, which
      include the majority of those grown as grain crops, light is a major modulator of
      defense responses. Light signals that indicate proximity of competitors, such as
      a low red to far-red (R:FR) ratio, down-regulate the expression of JA- and SA
      induced immune responses against pests and pathogens. This down-regulation of
      defense under low R:FR ratios, which is caused by the photoconversion of the
      photoreceptor phytochrome B (phyB) to an inactive state, is likely to help the
      plant to efficiently redirect resources to rapid growth when the competition
      threat posed by neighboring plants is high. This review is focused on the
      molecular mechanisms that link phyB with defense signaling. In particular, we
      discuss novel signaling players that are likely to play a role in the repression
      of defense responses under low R:FR ratios. A better understanding of the
      molecular connections between photoreceptors and the hormonal regulation of plant
      immunity will provide a functional framework to understand the mechanisms used by
      plants to deal with fundamental resource allocation trade-offs under dynamic
      conditions of biotic stress. 

PMID- 25063025
TI  - Plasminogen activator inhibitor-1 regulates infiltration of macrophages into
      melanoma via phosphorylation of FAK-Tyr925.
AB  - Tumor-infiltrating macrophages are potential candidates for cancer immunotherapy.
      However, the detailed molecular mechanism underlying macrophage infiltration into
      tumors is poorly understood. Based on our previous finding that plasminogen
      activator inhibitor-1 (PAI-1) enhances vitronectin-dependent migration of
      macrophages, we investigated the potential role of PAI-1 in macrophage invasion
      into melanoma. Experimental evidence obtained from spheroid confrontation assay
      clearly showed that PAI-1 overexpression significantly enhanced the invasion of
      RAW 264.7 cells into B16F10 melanoma. We further demonstrated that PAI-1 induces
      phosphorylation of focal adhesion kinase (FAK) at Tyr(925), which, in turn,
      mediated the invasion of macrophages into the melanoma. This work further
      illustrates that low-density lipoprotein receptor related-protein 1 (LRP1) is
      essential for PAI-1-mediated FAK phosphorylation and macrophage invasion into
      melanoma. In conclusion, our study demonstrates a novel role of PAI-1 in
      macrophage invasion into melanoma and provides insights into the underlying
      molecular mechanism.

PMID- 25063026
TI  - Protecting capacity against malaria of chemically defined tetramer forms based on
      the Plasmodium falciparum apical sushi protein as potential vaccine components.
AB  - Developing novel generations of subunit-based antimalarial vaccines in the form
      of chemically-defined macromolecule systems for multiple antigen presentation
      represents a classical problem in the field of vaccine development. Many efforts
      involving synthesis strategies leading to macromolecule constructs have been
      based on dendrimer-like systems, the condensation of large building blocks and
      conventional asymmetric double dimer constructs, all based on lysine cores. This
      work describes novel symmetric double dimer and condensed linear constructs for
      presenting selected peptide multi-copies from the apical sushi protein expressed
      in Plasmodium falciparum. These molecules have been proved to be safe and
      innocuous, highly antigenic and have shown strong protective efficacy in rodents
      challenged with two Plasmodium species. Insights into systematic design,
      synthesis and characterisation have led to such novel antigen systems being used
      as potential platforms for developing new anti-malarial vaccine candidates. 

PMID- 25063027
TI  - GPER mediated estradiol reduces miR-148a to promote HLA-G expression in breast
      cancer.
AB  - Breast cancer is the most common malignant diseases in women. miR-148a plays an
      important role in regulation of cancer cell proliferation and cancer invasion and
      down-regulation of miR-148a has been reported in both estrogen receptor (ER)
      positive and triple-negative (TN) breast cancer. However, the regulation
      mechanism of miR-148a is unclear. The role of estrogen signaling, a signaling
      pathway is important in development and progression of breast cancer. Therefore,
      we speculated that E2 may regulate miR-148a through G-protein-coupled estrogen
      receptor-1 (GPER). To test our hypothesis, we checked the effects of E2 on miR
      148a expression in ER positive breast cancer cell MCF-7 and TN cancer cell MDA-MB
      231. Then we used GPER inhibitor G15 to investigate whether GPER is involved in
      regulation of E2 on miR-148a. Furthermore, we analyzed whether E2 affects the
      expression of HLA-G, which is a miR-148a target gene through GPER. The results
      showed that E2 induces the level of miR-148a in MCF-7 and MDA-MB-231 cells, GPER
      mediates the E2-induced increase in miR-148a expression in MCF-7 and MDA-MB-231
      cells and E2-GPER regulates the expression of HLA-G by miR-148a. In conclusion,
      our findings offer important new insights into the ability of estrogenic GPER
      signaling to trigger HLA-G expression through inhibiting miR-148a that supports
      immune evasion in breast cancer. 

PMID- 25063028
TI  - Increased activity of osteocyte autophagy in ovariectomized rats and its
      correlation with oxidative stress status and bone loss.
AB  - OBJECTIVES: The objectives of the present study were to investigate ovariectomy
      on autophagy level in the bone and to examine whether autophagy level is
      associated with bone loss and oxidative stress status. METHODS: 36 female Sprague
      Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized
      (OVX) rats treated either with vehicle or 17-beta-estradiol. At the end of the
      six-week treatment, bone mineral density (BMD) and bone micro-architecture in
      proximal tibias were assessed by micro-CT. Serum 17beta-estradiol (E2) level were
      measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD)
      activity, catalase (CAT) activity in proximal tibia was also determined. The
      osteocyte autophagy in proximal tibias was detected respectively by Transmission
      Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR
      and Western blot. In addition, the spearman correlation between bone mass,
      oxidative stress status, serum E2 and autophagy were analyzed. RESULTS:
      Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while
      decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT,
      and SOD. Treatment with E2 prevented the reduction in bone mass as well as
      restored the autophagy level. Furthermore, LC3-II expression was inversely
      correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation
      between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found.
      CONCLUSIONS: Ovariectomy induced oxidative stress, autophagy and bone loss.
      Autophagy of osteocyte was inversely correlated with oxidative stress status and
      bone loss.

PMID- 25063029
TI  - Pyrrolidinium fullerene induces apoptosis by activation of procaspase-9 via
      suppression of Akt in primary effusion lymphoma.
AB  - Primary effusion lymphoma (PEL) is a subtype of non-Hodgkin's B-cell lymphoma and
      is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus
      (KSHV) in immunosuppressed patients. In general, PEL cells are derived from post
      germinal center B-cells and are infected with KSHV. To evaluate potential novel
      anti-tumor compounds against KSHV-associated PEL, seven water-soluble fullerene
      derivatives were evaluated as potential drug candidates for the treatment of PEL.
      Herein, we discovered a pyrrolidinium fullerene derivative, 1,1,1',1'-tetramethyl
      [60]fullerenodipyrrolidinium diiodide, which induced apoptosis of PEL cells via a
      novel mechanism, the caspase-9 activation by suppressing the caspase-9
      phosphorylation, causing caspase-9 inactivation. Pyrrolidinium fullerene
      treatment reduced significantly the viability of PEL cells compared with KSHV
      uninfected lymphoma cells, and induced the apoptosis of PEL cells by activating
      caspase-9 via procaspase-9 cleavage. Pyrrolidinium fullerene additionally reduced
      the Ser473 phosphorylation of Akt and Ser196 of procaspase-9. Ser473
      phosphorylated Akt (i.e., activated Akt) phosphorylates Ser196 in procaspase-9,
      causing inactivation of procaspase-9. We also demonstrated that Akt inhibitors
      suppressed the proliferation of PEL cells compared with KSHV-uninfected cells.
      Our data therefore suggest that Akt activation is essential for cell survival in
      PEL and a pyrrolidinium fullerene derivative induced apoptosis by activating
      caspase-9 via suppression of Akt in PEL cells. In addition, we evaluated whether
      pyrrolidinium fullerene in combination with the HSP90 inhibitor (geldanamycin;
      GA) or valproate, potentiated the cytotoxic effects on PEL cells. Compared to
      treatment with pyrrolidinium fullerene alone, the addition of low-concentration
      GA or valproate enhanced the cytotoxic activity of pyrrolidinium fullerene. These
      results indicate that pyrrolidinium fullerene could be used as a novel therapy
      for the treatment of PEL. 

PMID- 25063030
TI  - Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric
      adenocarcinoma.
AB  - Gastric cancer is one of the major causes of cancer death worldwide; however, the
      mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA
      HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of
      metastasis in various cancers including gastric cancer. Here we investigated the
      impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the
      carcinogenesis of gastric cancer. We examined the mechanism of invasion and
      metastasis and analyzed the clinical significance of HOTAIR. Downregulation of
      HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was
      significantly elevated in various gastric cancer cell lines and tissues compared
      to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74,
      and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III
      cells. Lymphovascular invasion and lymph node metastasis were more common in the
      high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and
      migration. si-HOTAIR led to differential expression of epithelial to mesenchymal
      transition markers. We found that HOTAIR was involved in inhibition of apoptosis
      and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and
      progression of gastric cancer. 

PMID- 25063031
TI  - Direct contacts with colon cancer cells regulate the differentiation of bone
      marrow mesenchymal stem cells into tumor associated fibroblasts.
AB  - Tumor-stroma interactions are referred to as essential events in tumor
      progression. There has been growing attention that bone marrow-derived
      mesenchymal stem cells (BMSCs) can travel to tumor stroma, where they
      differentiate into tumor-associated fibroblast (TAF)-like cells, a predominant
      tumor-promoting stromal cell. However, little is definitively known about the
      contributors for this transition. Here, using an in vitro direct co-culture model
      of colon cancer cells and BMSCs, we identify that colon cancer cells can induce
      adjoining BMSCs to exhibit the typical characteristic of TAFs, with increased
      expression of alpha-smooth muscle actin (alpha-SMA). Importantly, the present
      data also reveals that activated Notch signaling mediates transformation of BMSCs
      to TAFs through the downstream TGF-beta/Smad signaling pathway. 

PMID- 25063032
TI  - Overexpression of Mps1 in colon cancer cells attenuates the spindle assembly
      checkpoint and increases aneuploidy.
AB  - The spindle assembly checkpoint kinase Mps1 is highly expressed in several types
      of cancers, but its cellular involvement in tumorigenesis is less defined.
      Herein, we confirm that Mps1 is overexpressed in colon cancer tissues. Further,
      we find that forced expression of Mps1 in the colon cancer cell line SW480
      enables cells to become resistant to both Mps1 inhibition-induced checkpoint
      depletion and cell death. Overexpression of Mps1 also increases genome
      instability in tumor cells owing to a weakened spindle assembly checkpoint.
      Collectively, our findings suggest that high levels of Mps1 contribute to
      tumorigenesis by attenuating the spindle assembly checkpoint.

PMID- 25063033
TI  - Salidroside inhibits oxygen glucose deprivation (OGD)/re-oxygenation-induced H9c2
      cell necrosis through activating of Akt-Nrf2 signaling.
AB  - Oxygen glucose deprivation (OGD)/re-oxygenation has been applied to cultured
      cardiomyocytes to create a cellular model of ischemic heart damage. In the
      current study, we explored the potential role of salidroside against OGD/re
      oxygenation-induced damage in H9c2 cardiomyocytes, and studied the underlying
      mechanisms. We found that OGD/re-oxygenation primarily induced necrosis in H9c2
      cells, which was inhibited by salidroside. Salidroside suppressed OGD/re
      oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial
      translocation and cyclophilin D (Cyp-D) association as well as mitochondrial
      membrane potential (MMP) decrease in H9c2 cells. Meanwhile, salidroside activated
      Akt and promoted transcription of NF-E2-related factor 2 (Nrf2)-regulated genes
      (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1)). Significantly,
      Nrf2 shRNA knockdown or Akt inhibitors (LY 294002 and wortmannin) not only
      prevented salidroside-induced HO-1/NQO-1 transcription, but also alleviated
      salidroside-mediated cytoprotective effect against OGD/re-oxygenation in H9c2
      cells. These observations suggest that salidroside activates Nrf2-regulated anti
      oxidant signaling, and protects against OGD/re-oxygenation-induced H9c2 cell
      necrosis via activation of Akt signaling. 

PMID- 25063034
TI  - The efficacy of nimodipine drug delivery using mPEG-PLA micelles and mPEG
      PLA/TPGS mixed micelles.
AB  - OBJECTIVE: In order to develop and compare mPEG-PLA micelles and mPEG-PLA/TPGS
      mixed micelles, with the intention to develop a highly efficient formulation for
      nimodipine (NIM), NIM-loaded micelles and mixed micelles were made and their
      pharmacokinetics were studied. METHODS: Single factor experiments and orthogonal
      experiments were designed to optimize the final preparation process,
      characterizations and drug release behaviors were studied. Pharmacokinetics of
      NIM micelles, NIM mixed micelles were researched and were compared to NIM
      solution. RESULTS: Micelles and mixed micelles were prepared by solvent
      evaporation method, with relatively high drug loading efficiency and within nano
      particle size range. The CMC value of mPEG-PLA was lower than that of mPEG
      PLA/TPGS. The results of FTIR and TEM confirmed the spherical core-shell
      structure of micelles as well as mixed micelles, and the encapsulation of NIM
      inside the cores. In vitro release showed that micelles and mixed micelles had
      sustained release effect in the forms of passive diffusion and dissolution
      process, respectively. Following intraperitoneal administration (5mg/kg),
      micelles and mixed micelles were absorbed faster than solution, and with larger
      MRT(0-t), smaller CLz and larger AUC(0-t) as compared to that of solution, which
      showed micelles and mixed micelles had higher retention, slower elimination and
      higher bioavailability. This experiment also showed that mixed micelles released
      NIM more stably than micelles. By evaluate the bioequivalence, NIM micelles and
      NIM mixed micelles were testified non-bioequivalent to NIM solution. CONCLUSION:
      Micelles and mixed micelles could sustain the NIM concentrations more efficiently
      in plasma as compared to solution. Mixed micelles were the best ones since they
      had high loading content and released more stably. Thus, apprehending micelles
      and mixed micelles were suited as poor aqueous solubility drug carriers, and
      mixed micelles were better due to their high loading content and more stable
      release.

PMID- 25063035
TI  - Human and simulated intestinal fluids as solvent systems to explore food effects
      on intestinal solubility and permeability.
AB  - The mixed micelles and vesicles present in the intraluminal environment of the
      postprandial state exhibit suitable solubilizing capacities for lipophilic drugs.
      This increase in solubility, however, is accompanied by a decrease in the free
      fraction caused by micellar entrapment of these lipophilic compounds. In this
      study, both simulated and aspirated human intestinal fluids of fasted and fed
      state conditions were used to evaluate the influence of food on the intestinal
      disposition of a series of structurally related beta-blockers, with varying logP
      values. Using the in situ intestinal perfusion technique with mesenteric blood
      sampling in rats, it was demonstrated that fed state conditions significantly
      decreased the absorptive flux of the more lipophilic compounds metoprolol,
      propranolol and carvedilol, whereas the influence on the flux of the hydrophilic
      beta-blocker atenolol was limited. The solubility of BCS class II compound
      carvedilol was found to increase significantly in simulated and aspirated media
      of the fed state. Intestinal perfusions using intestinal media saturated with
      carvedilol, revealed a higher flux in the fasted state compared to the fed state,
      despite the higher solubility in the fed state. This study underscores the
      importance of addressing the complex nature of the behavior of compounds in the
      intraluminal environment in fasted and fed state conditions. Moreover, our data
      point out the value of studying the effect of food on both solubility and
      permeability using biorelevant experimental conditions. 

PMID- 25063039
TI  - 18F-Fluorocholine PET/CT for localization of hyperfunctioning parathyroid tissue
      in primary hyperparathyroidism: a pilot study.
AB  - PURPOSE: Primary hyperparathyroidism is a common endocrine disorder which is
      diagnosed biochemically and for which therapy is surgical. A prerequisite for
      minimally invasive surgery, which minimizes morbidity and cost, is accurate
      localization of the involved gland(s). The aim of this study was to evaluate the
      usefulness of (18)F-fluorocholine PET/CT for preoperative localization of
      hyperfunctioning parathyroid tissue. METHODS: (18)F-Fluorocholine PET/CT and
      conventional parathyroid scintigraphic imaging consisting of (99m)Tc-sestaMIBI
      SPECT/CT, (99m)Tc-sestaMIBI dual-phase imaging and (99m)Tc
      sestaMIBI/pertechnetate subtraction imaging were performed in 24 patients. The
      diagnostic performance of the imaging methods was compared against histology as
      the gold standard and postoperative serum Ca(2+) and iPTH values. RESULTS: The
      sensitivity and specificity of (18)F-fluorocholine PET/CT were 92% and 100%,
      respectively, in contrast to 49% and 100%, 46% and 100%, and 44% and 100% for
      (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI/pertechnetate subtraction imaging
      and (99m)Tc-sestaMIBI dual-phase imaging, respectively. Combined conventional
      scintigraphic imaging had a sensitivity and specificity of 64% and 100%,
      respectively. The performance of (18)F-fluorocholine PET/CT was superior
      particularly in patients with multiple lesions or hyperplasia. CONCLUSION: (18)F
      Fluorocholine PET/CT appears to be a promising, effective imaging method for
      localization of hyperfunctioning parathyroid tissue.

PMID- 25063040
TI  - In-vivo comparison of the acute retention of stem cell derivatives and
      fibroblasts after intramyocardial transplantation in the mouse model.
AB  - PURPOSE: Various strategies have been applied to increase the engraftment of an
      intramyocardial cell transplant (Tx) to treat ischemic myocardium. Thereby, co
      transplanted fibroblasts (FB) improve the long-term survival of stem cell
      derivatives (SCD) in a murine model of myocardial infarction. For therapeutic
      use, the time frame in which FB exert putative supportive effects needs to be
      identified. Therefore, we tracked the biodistribution and retention of SCD and FB
      in vivo using highly sensitive positron emission tomography (PET) imaging.
      METHODS: Murine [(18)F]-fluorodeoxyglucose (FDG) labeled SCD and FB were
      transplanted after left anterior descending artery (LAD) ligation into the border
      zone of the ischemic area in female C57BL/6 mice. Cardiac retention and
      biodistribution during the initial 2 h after injection were measured via PET
      imaging. RESULTS: Massive initial cell loss occurred independently of the cell
      type. Thereby, FB were retained slightly, yet significantly better than SCD until
      60 min post-injection (7.5 +/- 1.7 vs. 5.2 +/- 0.7% ID at 25 min and 7.0 +/- 1.5
      vs. 4.8 +/- 0.8% ID at 60 min). Thereafter, a fraction of ~ 5% that withstood the
      massive initial washout remained at the site of injection independently of the
      applied cell type (120 min, SCD vs. FB P = 0.64). Most of the lost cells were
      detected in the lungs (~ 30 % ID). CONCLUSIONS: We were able to quantitatively
      define the retention and biodistribution of different cell types via PET imaging
      in a mouse model after intramyocardial Tx. The utmost accuracy was achieved
      through this cell- and organ-specific approach by correcting PET data for
      cellular FDG efflux. Thereby, we observed a massive initial cell loss of ~ 95%,
      causing low rates of long-term engraftment for both SCD and FB. We conclude that
      FB are not privileged compared to SCD regarding their acute retention kinetics,
      and therefore exert their beneficial effects at a later time point.

PMID- 25063041
TI  - Effects of Korean red ginseng (Panax Ginseng Meyer) on bisphenol A exposure and
      gynecologic complaints: single blind, randomized clinical trial of efficacy and
      safety.
AB  - BACKGROUND: Korean red ginseng (KRG) is a processed ginseng from raw ginseng to
      enhance safety, preservation and efficacy, known having beneficial effects on
      women's health due to its estrogen like function. While estrogen supplementation
      showed some modulation of endocrine disrupting chemicals, bisphenol A (BPA) has
      been focused as a potential endocrine disrupting chemical. In this study, we
      examined the efficacy and safety outcomes of KRG against BPA, focusing on female
      quality of life (QOL). Individual variations in susceptibility to KRG were also
      investigated with the Sasang Typology, the personalized medicine used for hundred
      years in Korea. METHODS: We performed a single-blind randomized clinical trial.
      Study subjects were young women (N = 22), consumed 2.7 g of KRG or placebo per
      day for 2 weeks and filled up questionnaires regarding gynecologic complaints at
      the 4 time spots. We analyzed urinary total BPA and malondialdehyde (MDA), an
      oxidative stress biomarker, with GC/MS and HPLC/UVD respectively, and diagnosed
      their Sasang Typology with the questionnaire for the Sasang constitution
      Classification (QSCC II). RESULTS: KRG consumption decreased urinary BPA and MDA
      levels (ps < 0.05) and alleviated 'menstrual irregularity', 'menstrual pain', and
      'constipation' (ps < 0.05). SoEum type (Lesser Yin person) among the Sasang types
      showed significant alleviation in insomnia, flushing, perspiration and appetite
      by KRG consumption, rather than other Sasang types. During the intervention, no
      one experienced any aggravated side effects. CONCLUSION: We suggest KRG is
      efficient for protection for female QOL and BPA- exposure and - related oxidative
      stress. However, individual variation in susceptibility to KRG should be further
      considered for identifying ideal therapy. TRIAL REGISTRATION: KCT0000920.

PMID- 25063042
TI  - Microarray analysis reveals global modulation of endogenous retroelement
      transcription by microbes.
AB  - BACKGROUND: A substantial proportion of both the mouse and human genomes comprise
      of endogenous retroelements (REs), which include endogenous retroviruses. Over
      evolutionary time, REs accumulate inactivating mutations or deletions and thus
      lose the ability to replicate. Additionally, REs can be transcriptionally
      repressed by dedicated mechanisms of the host. Nevertheless, many of them still
      possess and express intact open reading frames, and their transcriptional
      activity has been associated with many physiological and pathological processes
      of the host. However, this association remains tenuous due to incomplete
      understanding of the mechanism by which RE transcription is regulated. Here, we
      use a bioinformatics tool to examine RE transcriptional activity, measured by
      microarrays, in murine and human immune cells responding to microbial
      stimulation. RESULTS: Immune cell activation by microbial signals in vitro caused
      extensive changes in the transcription not only of the host genes involved in the
      immune response, but also of numerous REs. Modulated REs were frequently found
      near or embedded within similarly-modulated host genes. Focusing on probes
      reporting single-integration, intergenic REs, revealed extensive transcriptional
      responsiveness of these elements to microbial signals. Microbial stimulation
      modulated RE expression in a cell-intrinsic manner. In line with these results,
      the transcriptional activity of numerous REs followed characteristics in
      different tissues according to exposure to environmental microbes and was further
      heavily altered during viral infection or imbalances with intestinal microbiota,
      both in mice and humans. CONCLUSIONS: Together, these results highlight the
      utility of improved methodologies in assessing RE transcription profiles in both
      archived and new microarray data sets. More importantly, application of this
      methodology suggests that immune activation, as a result of infection with
      pathogens or dysbiosis with commensal microbes, causes global modulation of RE
      transcription. RE responsiveness to external stimuli should, therefore, be
      considered in any association between RE transcription and disease.

PMID- 25063043
TI  - Statistical approaches for enhancing causal interpretation of the M to Y relation
      in mediation analysis.
AB  - Statistical mediation methods provide valuable information about underlying
      mediating psychological processes, but the ability to infer that the mediator
      variable causes the outcome variable is more complex than widely known.
      Researchers have recently emphasized how violating assumptions about confounder
      bias severely limits causal inference of the mediator to dependent variable
      relation. Our article describes and addresses these limitations by drawing on new
      statistical developments in causal mediation analysis. We first review the
      assumptions underlying causal inference and discuss three ways to examine the
      effects of confounder bias when assumptions are violated. We then describe four
      approaches to address the influence of confounding variables and enhance causal
      inference, including comprehensive structural equation models, instrumental
      variable methods, principal stratification, and inverse probability weighting.
      Our goal is to further the adoption of statistical methods to enhance causal
      inference in mediation studies. 

PMID- 25063044
TI  - What is implicit self-esteem, and does it vary across cultures?
AB  - Implicit self-esteem (ISE), which is often defined as automatic self-evaluations,
      fuses research on unconscious processes with that on self-esteem. As ISE is
      viewed as immune to explicit control, it affords the testing of theoretical
      questions such as whether cultures vary in self-enhancement motivations. We
      provide a critical review and integration of the work on (a) the
      operationalization of ISE and (b) possible cultural variation in self-enhancement
      motivations. Although ISE measures do not often vary across cultures, recent meta
      analyses and empirical studies question the validity of the most common way of
      defining ISE. We revive an alternative conceptualization that defines ISE in
      terms of how positively people evaluate objects that reflect upon themselves.
      This conceptualization suggests that ISE research should target alternative
      phenomena (e.g., minimal group effect, similarity-attraction effect, endowment
      effect) and it allows for a host of previous cross-cultural findings to bear on
      the question of cultural variability in ISE. 

PMID- 25063045
TI  - Changes in serum creatinine in patients with active rheumatoid arthritis treated
      with tofacitinib: results from clinical trials.
AB  - INTRODUCTION: Small increases in mean serum creatinine (SCr) were observed in
      studies of rheumatoid arthritis patients during tofacitinib treatment. These SCr
      changes were investigated and potential mechanisms explored. METHODS: SCr values
      and renal adverse event data were pooled from five Phase 3 and two long-term
      extension (LTE) studies. Dose-response relationships and association with
      inflammation (C-reactive protein (CRP)) were explored using Phase 2 data and
      confirmed with Phase 3 data. RESULTS: In Phase 3, least squares mean SCr
      differences from placebo at Month 3 were 0.02 and 0.04 mg/dl for tofacitinib 5
      and 10 mg twice daily (BID) (P <0.05), respectively. During Months 0 to 3,
      confirmed SCr >=33% increases over baseline were reported in 17 (1.4%; 5 mg BID)
      and 23 (1.9%; 10 mg BID) patients. Generally, elevations plateaued and remained
      within normal limits throughout Phase 3 and LTE studies. Exposure-response
      modeling demonstrated small, reversible effects of tofacitinib on mean SCr, and
      significant (P <0.05) effects of CRP on model parameters. Phase 3 data confirmed
      that patients with higher baseline CRP or greater CRP decreases following
      tofacitinib treatment had the largest increases in SCr. Across Phase 3 and LTE
      studies, 22 tofacitinib-treated patients had clinical acute renal failure (ARF),
      predominantly in the setting of concurrent serious illness. CONCLUSIONS:
      Tofacitinib treatment was associated with small, reversible mean increases in SCr
      that plateaued early. The mechanism behind these SCr changes remains unknown, but
      may involve effects of tofacitinib on inflammation. ARF occurred infrequently,
      was associated with concurrent serious illness, and was unrelated to prior SCr
      increases.

PMID- 25063046
TI  - Genetic structure and biological properties of the first ancient multiresistance
      plasmid pKLH80 isolated from a permafrost bacterium.
AB  - A novel multidrug-resistance plasmid, pKLH80, previously isolated from
      Psychrobacter maritimus MR29-12 found in ancient permafrost, was completely
      sequenced and analysed. In our previous studies, we focused on the pKLH80 plasmid
      region containing streptomycin and tetracycline resistance genes, and their
      mobilization with an upstream-located ISPpy1 insertion sequence (IS) element.
      Here, we present the complete sequence of pKLH80 and analysis of its backbone
      genetic structure, including previously unknown features of the plasmid's
      accessory region, notably a novel variant of the beta-lactamase gene blaRTG-6.
      Plasmid pKLH80 was found to be a circular 14 835 bp molecule that has an overall
      G+C content of 40.3 mol% and encodes 20 putative ORFs. There are two distinctive
      functional modules within the plasmid backbone sequence: (i) the replication
      module consisting of repB and the oriV region; and (ii) the mobilization module
      consisting of mobA, mobC and oriT. All of the aforementioned genes share sequence
      identities with corresponding genes of different species of Psychrobacter. The
      plasmid accessory region contains antibiotic resistance genes and IS elements
      (ISPsma1 of the IS982 family, and ISPpy1 and ISAba14 of the IS3 family) found in
      environmental and clinical bacterial strains of different taxa. We revealed that
      the sequences flanking blaRTG-6 and closely related genes from clinical bacteria
      are nearly identical. This fact suggests that blaRTG-6 from the environmental
      strain of Psychrobacter is a progenitor of blaRTG genes of clinical bacteria. We
      also showed that pKLH80 can replicate in different strains of Acinetobacter and
      Psychrobacter genera. The roles of IS elements in the horizontal transfer of
      antibiotic resistance genes are examined and discussed. 

PMID- 25063047
TI  - A validation study of 5 triage systems using data from the 2005 Graniteville,
      South Carolina, chlorine spill.
AB  - INTRODUCTION: Lack of outcomes-based research results in uncertainty about the
      effectiveness of any of the current triage systems in determining priority of
      care during actual chemical disasters. The purpose of this study was to determine
      whether the level of injury severity extrapolated from 5 triage systems
      correlated with actual injury severity outcomes of victims exposed to a chlorine
      disaster. METHODS: Using secondary data analysis, data for 631 victims were
      merged, de-identified, and analyzed. Using logic models from the triage systems,
      the actual injury severity was compared with the extrapolated injury severity
      classifications. RESULTS: Analysis showed weak to modest correlations between the
      extrapolated injury severity triage outcome classifications and the actual injury
      severity outcomes (Spearman correlation range 0.38 to 0.71, P < .0001). There was
      slight to fair agreement between the extrapolated injury severity triage outcome
      classifications and the actual injury severity outcomes (weighted kappa = - 0.23
      to 0.42). DISCUSSION: The extrapolated injury severity triage outcome categories
      from the 5 triage systems did not agree with the actual injury severity
      categories. Oxygen saturation measured by pulse oximetry provides early
      indications and is very predictive of outcome severity in incidents involving
      irritant chemical exposures such as chlorine, and should be a part of a mass
      casualty protocol for any irritant chemical incident. Additional research is
      needed to identify the most sensitive clinical measures for triaging victims of
      toxic inhalation disasters.

PMID- 25063048
TI  - Fingolimod: a review of its use in relapsing-remitting multiple sclerosis.
AB  - Fingolimod (Gilenya((r))) is an orally administered disease modifying agent (DMA)
      for use in relapsing-remitting multiple sclerosis (RRMS). In placebo-controlled
      trials in patients with RRMS with active disease, fingolimod 0.5 mg/day
      significantly reduced the annualized relapse rate (ARR) by approximately one-half
      over 2-year trial periods. It also significantly increased the proportion of
      patients with no disability progression, reduced deterioration from baseline in
      the Extended Disability Status Scale score and reduced MRI markers of disease
      progression (new/newly enlarging brain lesions and percentage change in brain
      volume). In a 12-month, comparison with intramuscular interferon beta-1a (IFNbeta
      1a) 30 MUg/week, the ARR in fingolimod 0.5 mg/day recipients was significantly
      lower than in IFNbeta-1a recipients by one-half; fingolimod recipients also had
      significantly lower MRI markers of disease progression. In extensions to the
      pivotal clinical trials, fingolimod exposure for up to 4 years was associated
      with low relapse rates and continuing benefits in terms of disability and disease
      progression. In clinical trials, adverse events in fingolimod recipients were
      generally mild to moderate in severity. In the pivotal placebo-controlled trial,
      serious adverse events occurred in similar proportions of fingolimod 0.5 mg/day
      and placebo recipients. First-dose bradycardia and atrioventricular block, which
      are generally asymptomatic, were clinically important adverse events associated
      with fingolimod in placebo-controlled trials. The risk for serious cardiovascular
      adverse events at the approved fingolimod dosage appears to be low in patients
      without pre-existing cardiac conditions. Fingolimod is an efficacious therapy for
      RRMS that reduces relapses, disability progression, new brain lesions and loss of
      brain volume. It has an acceptable tolerability profile and provides a useful
      alternative treatment in patients with RRMS who have responded poorly to other
      DMAs.

PMID- 25063049
TI  - Melanogenesis inhibitory effect of aerial part of Pueraria thunbergiana in vitro
      and in vivo.
AB  - Melanin is major factor that determines skin color as well as one of the defense
      systems that prevent the UV-induced damage. In case of abnormal concentration of
      melanin, skin diseases or problems occur such as albinism, leukoplakia, melasma,
      freckles, moles, and lentigo. With the lifespan of humans has been extended,
      importance of 'life quality' has been increased. White and clean skin is very
      important part of the satisfaction of appearance, especially for Asia women. The
      aim of this study was to find an anti-melanogenesis activity for which the aerial
      part of Pueraria thunbergiana can be utilized based on the increase in demands
      for cosmetics, particularly natural products. We demonstrated anti-pigmentation
      effects of aerial part of P. thunbergiana by measuring melanin content and
      through staining in the B16F10 melanoma cell line. The aerial part of P.
      thunbergiana decreased tyrosinase activity significantly in B16F10 cell cultures,
      while there is no direct effect on enzyme in cell-free conditions. To define the
      mechanisms, real-time PCR, western blot, glucosidase activity and antioxidant
      activity assay were implemented. As results, we demonstrated that aerial part of
      P. thunbergiana has anti-melanogenesis activity via two mechanisms. One is
      downgrading microphthalmia-associated transcription factor by activating Akt/GSK
      3beta. Consequently, transcription of tyrosinase and tyrosinase-related protein 1
      is decreased. Another is interrupting maturation of tyrosinase through inhibiting
      alpha-glucosidase. Furthermore, aerial part of P. thunbergiana showed great
      efficacy on pigmentation in vivo. These results suggest that aerial part of P.
      thunbergiana can be used as an anti-melanogenic agent. 

PMID- 25063050
TI  - A mobile system for quantifying the spatial variability of the surface energy
      balance: design and application.
AB  - We present a mobile device for the quantification of the small-scale (a few
      square meters) spatial variability in the surface energy balance components and
      several auxiliary variables of short-statured (<1 m) canopies. The key element of
      the mobile device is a handheld four-component net radiometer for the
      quantification of net radiation, albedo and infrared surface temperature, which
      is complemented with measurements of air temperature, wind speed, soil
      temperature and soil water content. Data are acquired by a battery-powered data
      logger, which is mounted on a backpack together with the auxiliary sensors. The
      proposed device was developed to bridge between the spatial scales of
      satellite/airborne remote sensing and fixed, stationary tower-based measurements
      with an emphasis on micrometeorological, catchment hydrological and landscape
      ecological research questions. The potential of the new device is demonstrated
      through four selected case studies, which cover the issues of net radiation
      heterogeneity within the footprint of eddy covariance flux measurements due to
      (1) land use and (2) slope and aspect of the underlying surface, (3) controls on
      landscape-scale variability in soil temperature and albedo and (4) the estimation
      of evapotranspiration based exclusively on measurements with the mobile device.

PMID- 25063051
TI  - Surgical management of early endometrial cancer: an update and proposal of a
      therapeutic algorithm.
AB  - In the last few years technical improvements have produced a dramatic shift from
      traditional open surgery towards a minimally invasive approach for the management
      of early endometrial cancer. Advancement in minimally invasive surgical
      approaches has allowed extensive staging procedures to be performed with
      significantly reduced patient morbidity. Debate is ongoing regarding the choice
      of a minimally invasive approach that has the most effective benefit for the
      patients, the surgeon, and the healthcare system as a whole. Surgical treatment
      of women with presumed early endometrial cancer should take into account the
      features of endometrial disease and the general surgical risk of the patient.
      Women with endometrial cancer are often aged, obese, and with cardiovascular and
      metabolic comorbidities that increase the risk of peri-operative complications,
      so it is important to tailor the extent and the radicalness of surgery in order
      to decrease morbidity and mortality potentially derivable from unnecessary
      procedures. In this regard women with negative nodes derive no benefit from
      unnecessary lymphadenectomy, but may develop short- and long-term morbidity
      related to this procedure. Preoperative and intraoperative techniques could be
      critical tools for tailoring the extent and the radicalness of surgery in the
      management of women with presumed early endometrial cancer. In this review we
      will discuss updates in surgical management of early endometrial cancer and also
      the role of preoperative and intraoperative evaluation of lymph node status in
      influencing surgical options, with the aim of proposing a management algorithm
      based on the literature and our experience.

PMID- 25063052
TI  - Rapid manufacturing techniques for the tissue engineering of human heart valves.
AB  - Three-dimensional (3D) printing technologies have reached a level of quality that
      justifies considering rapid manufacturing for medical applications. Herein, we
      introduce a new approach using 3D printing to simplify and improve the
      fabrication of human heart valve scaffolds by tissue engineering (TE). Custom
      made human heart valve scaffolds are to be fabricated on a selective laser
      sintering 3D printer for subsequent seeding with vascular cells from human
      umbilical cords. The scaffolds will be produced from resorbable polymers that
      must feature a number of specific properties: the structure, i.e. particle
      granularity and shape, and thermic properties must be feasible for the printing
      process. They must be suitable for the cell-seeding process and at the same time
      should be resorbable. They must be applicable for implementation in the human
      body and flexible enough to support the full functionality of the valve. The
      research focuses mainly on the search for a suitable scaffold material that
      allows the implementation of both the printing process to produce the scaffolds
      and the cell-seeding process, while meeting all of the above requirements.
      Computer tomographic data from patients were transformed into a 3D data model
      suitable for the 3D printer. Our current activities involve various aspects of
      the printing process, material research and the implementation of the cell
      seeding process. Different resorbable polymeric materials have been examined and
      used to fabricate heart valve scaffolds by rapid manufacturing. Human vascular
      cells attached to the scaffold surface should migrate additionally into the inner
      structure of the polymeric samples. The ultimate intention of our approach is to
      establish a heart valve fabrication process based on 3D rapid manufacturing and
      TE. Based on the computer tomographic data of a patient, a custom-made scaffold
      for a valve will be produced on a 3D printer and populated preferably by
      autologous cells. The long-term goal is to support the growth of a new valve by a
      3D structure resorbed by the human body in the course of the growth process. Our
      current activities can be characterized as basic research in which the
      fundamental steps of the technical process and its feasibility are investigated. 

PMID- 25063053
TI  - Des-acyl-ghrelin (DAG) normalizes hyperlactacidemia and improves survival in a
      lethal rat model of burn trauma.
AB  - Critical illness, including burn injury, results in elevated plasma lactate
      levels. Dysregulation of PI3K/Akt signaling has been shown to play a predominant
      role in the inactivation of skeletal muscle PDC and, hence, in hyperlactacidemia
      in rat models of sepsis and endotoxemia. This observation, and our previous
      finding that DAG can reverse burn-induced skeletal muscle proteolysis through the
      activation of PI3K/Akt pathway, led us to hypothesize that DAG may also attenuate
      hyperlactacidemia in burn injury. Our investigations revealed that burn injury
      significantly elevated both skeletal muscle lactate production and plasma lactate
      levels. Moreover, this was accompanied in skeletal muscle by a 5-7 fold increase
      in mRNA expression of pyruvate dehydrogenase kinases (PDK) 2 and 4, and a ~30%
      reduction in PDC activity. DAG treatment of burn rats completely normalized not
      only the mRNA expression of the PDKs and PDC activity, but also hyperlactacidemia
      within 24h of burn injury. DAG also normalized epinephrine-induced lactate
      production by isolated skeletal muscles from normal rats. Moreover, DAG also
      improved survival in a lethal rat model of burn trauma. These findings with DAG
      may have clinical implications because chances of survival for critically ill
      patients are greatly improved if plasma lactate levels are normalized within 24h
      of injury. 

PMID- 25063054
TI  - Physiological fluctuations of human plasma total salusin-beta, an endogenous
      parasympathomimetic/proatherosclerotic peptide.
AB  - Salusin-beta is an endogenous bioactive peptide that systemically exerts acute
      parasympathomimetic hemodynamic actions and locally induces atherogenesis. Due to
      its unique physicochemical characteristics to immediately adhere to all types of
      plastic and glassware, its plasma concentrations have only been successfully
      determined very recently. Using a total of 50 healthy adults (median age 28
      years, range 24-57 years), we evaluated whether circulating salusin-beta levels
      are affected by the autonomic nervous functions. Plasma total salusin-beta levels
      obtained during daytime ambulatory monitoring of heart rate variability showed
      strong negative correlations with variables reflecting parasympathetic nervous
      activity, high frequency amplitude (HF; r=-0.27, p=0.0018) and the square root of
      the mean squared differences of successive normal-to-normal intervals (RMSSD; r=
      0.19, p=0.0292), but did not with low frequency amplitude (LF) or LF/HF,
      variables influenced by sympathetic nervous activity. Because early morning nadir
      in the diurnal variation of plasma total salusin-beta levels appeared to follow
      the nighttime parasympathetic nervous activity peak as quantified by HF and
      RMSSD, we determined whether parasympathetic stimulation reduces plasma salusin
      beta levels. Both Valsalva maneuver (p<0.05) and urination (p<0.05) significantly
      reduced plasma total salusin-beta levels. Despite the fact that salusin-beta is
      the sole endogenous parasympathomimetic peptide identified to date, the current
      results argue against the contention that physiological parasympathetic
      augmentation is the consequences of upregulated circulating salusin-beta. Rather,
      circulating salusin-beta levels are suppressed following physiological
      parasympathetic stimulation and appear to constitute a negative feedback
      relationship with the parasympathetic nervous system. 

PMID- 25063055
TI  - Copeptin as a diagnostic biomarker for sepsis-related deaths.
AB  - Copeptin has been shown to increase in patients with sepsis, severe sepsis and
      septic shock. In the study herein described, copeptin was measured in a series of
      sepsis-related fatalities and control cases that underwent medico-legal
      investigations. No age-dependent differences in copeptin levels in either sepsis
      or control cases were observed. No correlation between copeptin concentrations
      and postmortem interval was identified in either group. Copeptin levels were
      significantly higher in sepsis cases. Moreover, copeptin concentrations in septic
      cases correlated with procalcitonin, C-reactive protein and interleukin 6 values.
      These preliminary findings seem to indicate that copeptin can be reliably
      measured in biological samples collected during postmortem investigations. These
      results also suggest that hemodynamic instability associated with sepsis and
      septic shock can be characterized by copeptin measurement also in the forensic
      casework. 

PMID- 25063056
TI  - Nitric oxide participates in the toxicity of Bacillus thuringiensis Cry1Ab toxin
      to kill Manduca sexta larvae.
AB  - Nitric oxide (NO) produced by the nitric oxide synthase (NOS) enzyme is a
      reactive oxygen molecule widely considered as important participant in the immune
      system of different organisms to confront microbial infections. In insects the NO
      molecule has also been implicated in immune response against microbial pathogens.
      Bacillus thuringiensis (Bt) is an insect-pathogenic bacterium that produces
      insecticidal proteins such as Cry toxins. These proteins kill insects because
      they form pores in the larval-midgut cells. Here we show that intoxication of
      Manduca sexta larvae with Cry1Ab activates expression of NOS with a corresponding
      increase in NO. This effect is not observed with a non-toxic mutant toxin Cry1Ab
      E129K that is affected in pore formation. The increased production of NO
      triggered by intoxication with LC50 dose of Cry1Ab toxin is not associated with
      higher expression of antimicrobial peptides. NO participates in Cry1Ab toxicity
      since inhibition of NOS by selective l-NAME inhibitor prevented NO production and
      resulted in reduced mortality of the larvae. The fact that mortality was not
      completely abolished by L-NAME indicates that other processes participate in
      toxin action and induction of NO production upon Cry1Ab toxin administration
      accounts only for a part of the toxicity of this protein to M. sexta larvae. 

PMID- 25063057
TI  - Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles
      conjugate on growth of human hepatocellular carcinoma: in vitro and in vivo
      studies.
AB  - OBJECTIVE: To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv
      As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma
      both in vitro and in vivo, which may be a potential agents with sensitivity and
      targeting ability for human hepatocellular cancer. METHODS: Humanized anti-VEGFR
      2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using
      ribosome display technology and antibody conjugate technology. In this combined
      in vitro and in vivo study, the inhibitory effects of anti-VEGFR-2 ScFv-As2O3
      stealth nanoparticles conjugate on tumor growth, invasion, and metastasis was
      observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT
      assay, Tanswell assay, Hochest33258 staining, and DNA ladder analysis. The
      anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth
      nanoparticles was then verified in a mouse model of Bel7402 xenografts. RESULTS:
      Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the
      proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay while had almost no effects on L02 cells. And
      the apoptosis inducing effects were proved by Hochest33258 staining and DNA
      ladder analysis. Transwell assay found that the drug also inhibited the
      metastasis ability of tumor cells. Furthermore, anti-VEGFR-2 ScFv-As2O3-stealth
      nanoparticles significantly delayed the growth of Bel7402 xenografts after
      administration (92.9%), followed by As2O3-stealth nanoparticles, anti-VEGFR-2
      ScFv, and As2O3 (61.4%, 58.8%, 20.5%, P<0.05). The concentration of As2O3 in anti
      VEGFR-2 ScFv-As2O3-stealth nanoparticles group was more selectively. CONCLUSIONS:
      Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti
      hepatocellular carcinoma agent which could inhibit the growth of liver cancer as
      a targeting agent both in vitro and in vivo and also significantly inhibit
      angiogenesis.

PMID- 25063058
TI  - Gene expression profiles associated with osteoblasts differentiated from bone
      marrow stromal cells.
AB  - OBJECTIVE: To study the changes of gene expression profiles associated with
      osteoblasts differentiated from rat bone marrow stromal cells in vitro by gene
      chip technique. METHODS: rat Bone marrow stromal cells were isolated and
      cultured, and differentiation was induced by dexamethasone, beta-glycerol
      phosphate and vitamin C. Cellular mRNA was extracted and reverse transcribed into
      cDNA, thus related genes expression differences were detected by gene expression
      profile chip. RESULTS: Calcifying nodules were visible in the induced cells.
      There were 27.7% genes expressed differentially, three times more than the normal
      and induced cells, and some genes were related to transcription, translation,
      glycosylation modification. Extracellular matrix, signal molecules and metabolism
      were up-regulated. CONCLUSIONS: The gene chip technique can be used to detect the
      multi-gene different expression in the differentiation-induced rat BMSCs, and
      these differentially expressed genes are necessary genes related to rat BMSCs
      proliferation and induction of osteoblastic differentiation.

PMID- 25063059
TI  - Effects of ultrasound-combined microbubbles on hippocampal AchE fibers in rats.
AB  - OBJECTIVE: To investigate the protective effect of ultrasound-combined
      microbubbles on hippocampal acetylcholinesterase (AchE) fibers in rats. METHODS:
      According to random digits table, 60 SD rats were divided into two groups, marrow
      stromal cells (MSCs) intracranial transplantation group and MSCs intracranial
      transplantation + ultrasonic microbubbles group. Marrow stromal cells were
      cultivated and isolated in vitro; 12 weeks after transplantation, spatial
      learning and memorizing abilities of rats were assessed by Morris water maze;
      AchE staining method was used to observe changes in density and appearance of
      AchE staining positive fibers in hippocampal CA1 region. RESULTS: There was a
      significant increase in spatial learning and memorizing abilities of rats in MSCs
      intracranial transplantation + ultrasonic microbubbles group. Hippocampal AchE
      staining suggested an increase in the density of AchE staining positive fibers in
      MSCs intracranial transplantation group; the fibers were regular, intact and
      dense. Density of hippocampal AchE positive fibers was negatively correlated with
      the escape latent period and was positively correlated with percentage of the
      time needed to cross each platform quadrant. CONCLUSIONS: Better promotion of
      spatial learning and memorizing abilities of rats in MSCs intracranial
      transplantation + ultrasonic microbubbles group may be related with the
      protective effect of ultrasound-combined microbubbles on hippocampal
      acetylcholine fibers.

PMID- 25063060
TI  - Decreased proliferation ability and differentiation potential of mesenchymal stem
      cells of osteoporosis rat.
AB  - OBJECTIVE: To explore decreased proliferation ability and differentiation
      potential of mesenchymal stem cells (MSCs) of osteoporosis rat. METHODS: MSCs
      were obtained from osteoporosis rat, and proliferation potency and impaired
      osteogenic differentiation potential were determined. RESULTS: The result showed
      a significant downregulation of MSCs pluripotency related gene (Oct 4) and
      osteogenic genes (BSP, OCN) expression in OVX MSCs compared with Sham MSCs
      (P<0.05). CONCLUSIONS: These data suggest that MSCs are aging in osteoporosis
      body, and autologous OVX MSCs transplantation is not appropriate to treat
      osteoporosis if necessary. There will be a possibility in establishing a new
      clinical application of MSCs autologous transplantation to treat osteoporosis, if
      OVX MSCs have stronger proliferation and differentiation.

PMID- 25063061
TI  - Effects of MicroRNA-10b on lung cancer cell proliferation and invasive metastasis
      and the underlying mechanism.
AB  - OBJECTIVE: To study the influence of MicroRNA-10b on proliferation and invasion
      of human low metastatic lung cancer cell 95-C and its mechanism. METHODS:
      Lipofectamine MicroRNA-10b eukaryotic expression plasmid was transfected into 95
      C. The experiment group was divided into blank control group, empty vector
      transfected group and MicroRNA-10b transfected group. Real time quantitative RT
      PCR was used to detect the expression of MicroRNA-10b and KLF4mRNA expression.
      Proliferations of cells were detected by cell proliferation assay, invasion of
      the detected the cell Transwell experiments, the expression of KLF4 protein was
      detected in Western blotting cells. RESULTS: The proliferation rate of MicroRNA
      10b plasmid transfection group increased significantly after transfection,
      invasion and migration ability enhancement, by comparison, there are
      statistically significant differences in the blank control group and negative
      control group (P<0.05); the expression of MicroRNA-10b plasmid transfection group
      KLF4 protein decreased, the difference was statistically significant (P<0.05);
      reduce the expression of MicroRNA-10b plasmid transfection group KLF4mRNA, but no
      significant differences (P>0.05). CONCLUSIONS: MicroRNA-10b may promote
      proliferation and invasion of 95-C cells by down regulating the expression of
      KLF4 protein.

PMID- 25063062
TI  - Effects of mTOR-STAT3 on the migration and invasion abilities of hepatoma cell
      and mTOR-STAT3 expression in liver cancer.
AB  - OBJECTIVE: To investigate the effects of mTOR-STAT3 pathway on the invasion and
      migration of hepatoma cell. METHODS: mTOR and STAT3 expression in the
      hepatocellular carcinoma cell line HepG2 and normal liver cell line L02 were
      detected by reverse transcription PCR (RT-PCR) and western blotting. The
      migration and invasion abilities of cells and expression of STAT3 were detected
      by scratch adhesion test and transwell migration assays, after siRNA transfection
      blocking mTOR expression of HepG2 cells. RESULTS: The HepG2 cells expression is
      higher compared with normal cells L02 expression. Western blotting assay showed
      the mTOR expression was blocked, while STAT3 expression was also decreased, after
      the siRNA transfection of HepG2 cells. The migration (scratch adhesion test) and
      invasion (transwell assays) abilities of HepG2 cells which the mTOR expression
      was blocked by siRNA interference were significantly decreased (P<0.05).
      CONCLUSION: mTORSTAT3 expression in hepatoma cells HepG2 was significantly higher
      than that in normal liver cells. mTOR blocking can reduce the expression of
      STAT3, which is also closely related to the invasion and metastasis of liver
      cancer cells.

PMID- 25063063
TI  - Silence of STIM1 attenuates the proliferation and migration of EPCs after
      vascular injury and its mechanism.
AB  - OBJECTIVE: To investigate the effect of stromal interaction molecule 1(STIM1)
      knockdown on the proliferation and migration of endothelial progenitor cells
      (EPCs) after vascular injury and its mechanism. METHODS: The rat bone marrow
      derived EPCs were divided into three groups: adenovirus negative control (group
      NSC), rat STIM1 adenovirus vector transfection group (group si/rSTIM1) and rat
      &human recombinant STIM1 adenovirus transfection group (group si/rSTIM1+hSTIM1).
      The STIM1 expressions in each group were detected by reverse transcription PCR
      after transfection; the cell proliferation was tested by [(3)H] thymidine
      incorporation assay ((3)H-TdR); Cell cycle was analyzed by flow cytometry; the
      cells' migration activity was detected by Boyden assay; Calcium ion concentration
      was detected by using laser confocal method. RESULTS: 48 h later after
      transfection, the expression level of STIM1 in si/rSTIM1 cells was significantly
      lower than that in NSC group (0.21 +/- 0.12 vs 1.01 +/- 0.01, P<0.05); EPCs that
      stayed in G1 phase in si/rSTIM1 group [(93.31 +/- 0.24)%] were significantly more
      than that in NSC group [(78.03 +/- 0.34)%, P<0.05]; EPCs' migration activity in
      si/rSTIM1 group (10.03+/-0.33) was significantly lower than that in NSC group:
      (32.11 +/- 0.54, P<0.05); EPCs calcium ion concentration changes in EPCs in
      si/rSTIM1 group (38.03 +/- 0.13) was significantly lower than that in NSC group
      (98.11 +/- 0.34, P<0.05). While there was no significant difference between
      si/rSTIM1+hSTIM1 group and NSC group on the four indexes above. CONCLUSIONS:
      Silence of STIM1 attenuates EPCs proliferation and migration after vascular
      injury, by mediating the calcium ion concentration in EPCs.

PMID- 25063064
TI  - Effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal
      cancer and its anti-tumor role.
AB  - OBJECTIVE: To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen
      deficiency in colorectal cancer and its anti-tumor role. METHODS: Human
      intestinal cancer cell HT29 xenograft of nude mice model was established. The
      expression of EGF, VEGF, gastric cancer tumor growth in mice were observed.
      RESULTS: Protein kinase C expression in in the Yiqi Jianpi group and Yiqi Jianpi
      anti-tumor group was significantly better than the model group (P<0.01, P<0.05).
      There was significantly more apoptotic cells in Yiqi Jianpi anti-tumor group than
      Yiqi Jianpi group and model group (P<0.01). Epidermal growth factor and vascular
      endothelial growth factor expression in Yiqi Jianpi group was significantly lower
      than Yiqi Jianpi group and model group (P<0.05). CONCLUSIONS: Tumor can inhibit
      the expression of PKC inhibition. Yiqi Jianpi and anticancer treatment can reduce
      this inhibition. Besides this treatment can also inhibit expression of tumor
      related genes such as epidermal growth factor and vascular endothelial growth
      factor.

PMID- 25063065
TI  - Reinforcing effect of calcium sulfate cement bovine bone morphogenetic protein on
      vertebral in the rabbit model of osteoporosis.
AB  - OBJECTIVE: To observe reinforcing effect of calcium sulfate cement (CSC) bovine
      bone morphogenetic protein (bBMP) on vertebral in the rabbit model of
      osteoporosis. METHODS: A total of 48 New Zealand white rabbits were randomly
      divided into group I (blank control group), group II (CSC injection group), group
      III (CSC/bBMP injection group) and control group. White rabbit osteoporosis model
      was established rapidly by using castration method+methylprednisolone candidate.
      After modeling, groups II, III were given corresponding vertebral body injection
      material, and 4 animals were sacrificed respectively at 24 h, 6 weeks, 12 weeks
      after vertebral plasty. Tissue pathological status, vertebral mineral density and
      vertebral body bone mechanical strength were observed. RESULTS: Vertebral body
      structure form was normal in the groups II and III. Trabecular bone coarsens,
      connection and repair were observed in micro fracture and bone defects, bone
      trabecular connectivity was superior to group I significantly; vertebral body
      compression strength in the group I was on the decline, vertebral compression
      strength in the groups II and III was on the rise, the largest vertebra.
      Postoperative BMC and BMD in groups II and III were increased, and significantly
      higher than group I after 6 weeks (P<0.05), BMC and BMD in group III after 12
      weeks were higher than the other three groups. CONCLUSION: Compound bBMP CSC has
      good bone induction. It can improve the three-dimensional construction effect for
      osteoporosis vertebral trabecula, and can significantly improve the vertebral
      strength, as a vertebral packing material with good application prospect.

PMID- 25063066
TI  - Expression of Bcl-2 and NF-kappaB in brain tissue after acute renal ischemia
      reperfusion in rats.
AB  - OBJECTIVE: To investigate the effect of acute renal ischemia reperfusion on brain
      tissue. METHODS: Fourty eight rats were randomly divided into four groups (n=12):
      sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia
      60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The
      brain tissues were taken after the experiment. TUNEL assay was used to detect the
      brain cell apoptosis, and western blot was used to detect the expression of
      apoptosis-related proteins and inflammatory factors. RESULTS: Renal ischemia
      reperfusion induced apoptosis of brain tissues, and the apoptosis increased with
      prolongation of ischemia time. The detection at the molecular level showed
      decreased Bcl-2 expression, increased Bax expression, upregulated expression of
      NF-kappaB and its downstream factor COX-2/PGE2. CONCLUSIONS: Acute renal ischemia
      reperfusion can cause brain tissue damage, manifested as induced brain tissues
      apoptosis and inflammation activation.

PMID- 25063067
TI  - Effect of matrine on transforming growth factor beta1 and hepatocyte growth
      factor in rat liver fibrosis model.
AB  - OBJECTIVE: To observe the preventive and control effect of matrine on
      transforming growth factor (TGF-beta1) and hepatocyte growth factor (HGF) of
      liver fibrosis tissue in rats. METHODS: A total of 48 SD rats were randomly
      divided into A, B, C, D groups with 12 in each, group A as the normal control
      group and groups B, C, D as liver fibrosis models using composite modulus method
      with carbon tetrachloride (CCL4). Group B was the model group, group C adopted
      gamma-interferon lavage therapy in the second day of modeling, and group D
      adopted matrine lavage treatment, at 4 and 8 weeks after treatment. Six rats were
      executed for detection of TGF-beta1 and HGF, liver tissue histology and
      comparison fibrosis degree changes of rat liver tissue between groups. RESULTS:
      Groups B, C, D showed a more significantly increased TGF-beta1 at each time point
      compared with group A (P<0.05); Group B showed a more significantly increased TGF
      beta1 than groups C and D at weeks 4 and 8 (P<0.05); group D showed a lowest
      level of TGF-beta1, followed by groups C and B. HGF of group B decreased more
      significantly than A group at weeks 4 and 8 (P<0.05); HGF of groups C and D was
      significantly elevated at 4 and 8 weeks than groups A and B (P<0.05), in which
      the group D showed the highest level of HGF. According to tissue histologic
      observation, rat liver tissue structure of group A was clear and normal, tissue
      structure of group B was destroyed with obvious fibrous tissue hyperplasia and
      fatty change of hepatic cells; groups C and D showed a slighter liver tissue
      damage, cell necrosis and connective tissue hyperplasia in collect abbacy than
      group B with a trend of obvious improvement. CONCLUSIONS: Matrine can reduce TGF
      beta1 expression and enhance the activity of HGF, so as to realize the inhibition
      effect on liver fibrosis in rats.

PMID- 25063068
TI  - In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC.
AB  - OBJECTIVE: To investigate the effect and mechanism of inhibitor everolimus on
      EGFR-TKI resistance NSCLC. METHODS: MTT assay was used to detect proliferation of
      human non-small cell lung cancer cell line A549. Flow cytometry was used to
      detect the changes of apoptosis and cycle distribution in each group after 24 h
      and 48 h. RT-PCR was used to detect the changes of PTEN and 4EBP1 expression
      levels after 48 h of monotherapy and combination therapy. RESULTS: MTT assay
      showed that everolimus had dose-dependent inhibition against growth of A549
      cells. Flow cytometry showed when everolimus could induce apoptosis and induce
      G0/G1 phase cell cycle arrest, which was time-dependent (P<0.05). RT-PCR showed
      everolimus could increase PTEN and 4EBP1 expression. CONCLUSIONS: mTOR inhibitor
      everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC, which cannot
      reverse the resistance effect of EGFR-TKI resistant cell line A549. The
      relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway
      and the mechanism in non-small cell lung cancer need further study.

PMID- 25063069
TI  - Effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic
      peptide expression in rats.
AB  - OBJECTIVE: To investigate the effect of atorvastatin on serum oxidative stress
      and N-terminal brain natriuretic peptide expression in rats. METHODS: A total of
      40 healthy male SD rats were randomly divided into the sham group (Group A, n=10,
      saline 5 mL/d), ischemia-reperfusion group (Group B, n=10, saline 5 mL/d),
      atorvastatin group (Group C, n=10, atorvastatin 20 mg/kg . d), atorvastatin + N
      amino-arginine group (Group D, n=10, atorvastatin 20 mg/kg . d + N-amino arginine
      15 mg/kg). Myocardial ischemia-reperfusion rat model was established after 3 days
      of gavage. N-amino arginine 15 mg/kg was given by tail vein injection 15 min
      before ischemia. After reperfusion, enzymology indicators such us creatine kinase
      (CK) and lactate dehydrogenase and the oxidative stress parameters such as nitric
      oxide (NO), malondialdehyde (MDA) and total superoxide dismutase (TSOD), and n
      terminal pro-brain natriuretic peptide (NT-proBNP) expression was detected by
      immunohistochemistry. RESULTS: LDH and CK levels of group A were significantly
      lower than the other three groups, and group B was the highest. There was
      significant difference between group B and group C (P<0.05), and no significant
      difference between group B and group D (P>0.05). MDA levels in group B were
      significantly higher than the other three groups. The lowest was group A,
      followed by group C, the difference among groups was significantly (P<0.05). TSOD
      and NO levels in group B was the lowest, the level in group A was the highest,
      followed by group C, the difference among groups was significant (P<0.05). NT
      proBNP level in group B was significantly higher than the other three groups, the
      lowest was group A, followed by group C, the difference among groups was
      significant (P<0.05). CONCLUSIONS: Atorvastatin has a protective effect on the
      myocardial injury in the myocardial ischemia and reperfusion rats. It can
      increase NO synthesis and decrease MDA content, increase serum TSOD activity and
      the oxidative stress effect, meanwhile protect myocardial cells and reduce
      myocardial injury.

PMID- 25063070
TI  - Protective effect of omeprazole on gastric mucosal of cirrhotic portal
      hypertension rats.
AB  - OBJECTIVE: To observe the protective effect of omeprazole on gastric mucosal of
      cirrhotic portal hypertension rats. METHODS: All rats were randomly divided into
      normal control group, cirrhosis and treatment group. Thioacetamide was used to
      establish rat model of cirrhotic portal hypertension. The necrotic tissue of
      gastric mucosa ulcer focus, degree of neutrophils infiltration at the ulcer
      margin, portal pressure, portal venous flow, abdominal aortic pressure, abdominal
      aortic blood flow at front end, gastric mucosal blood flow (GMBF), glycoprotein
      (GP) of gastric mucosa, basal acid secretion, H(+)back -diffusion, gastric
      mucosal damage index, NO, prostaglandin E2(PGE2) and tumor necrosis factor-alpha
      (TNF-alpha) were determined respectively, and the pathological changes of gastric
      mucosa were also observed by microscope. RESULTS: Compared with cirrhosis group
      and the control group, the ulcer bottom necrotic material, gastric neutrophil
      infiltration and UI of the treatment group were all decreased significantly
      (P<0.01), GMBF value, GP values, serum NO, PGE2, TNF-alpha were all significantly
      increased. CONCLUSIONS: Omeprazole has an important protective effect on gastric
      mucosal and it can increase gastric mucosal blood flow and related to many
      factors.

PMID- 25063072
TI  - Expression and distribution of TNF-alpha and PGE2 of periodontal tissues in rat
      periodontitis model.
AB  - OBJECTIVE: To simulate the expression of TNF-alpha and PGE2 of periodontal
      tissues in rat periodontitis model. METHODS: 40 Wistar rats were randomly divided
      into the periodontitis group and the control group (n=20). After the successful
      establishment of periodontitis rat model, raising for six weeks before the
      animals were sacrificed. The periodontal tissues were obtained and made into
      slices. Observed the histopathological changes of the periodontal tissues and
      measured TNF-alpha, PGE2 levels change by immunohistochemistry, Western blot
      analysis and ELISA. RESULTS: TNF-alpha, PGE2 expression of the periodontitis
      group was significantly higher than that in the control group, the difference was
      significant (P<0.05). CONCLUSIONS: The TNF-alpha, PGE2 expression of the rat
      periodontal tissue in the periodontitis group was significantly higher than the
      control group.

PMID- 25063074
TI  - What are randomised consent designs?

PMID- 25063071
TI  - Effect of propofol and ketamine anesthesia on cognitive function and immune
      function in young rats.
AB  - OBJECTIVE: To investigate the effects of propofol and ketamine on the cognitive
      function and immune function in young rats. METHOD: A total of 80 young rats were
      randomly divided into four groups: Control group, ketamine group (experimental
      group A), propofol group (experimental group B), ketamine and propofol group
      (experimental group C). All rats had continuous injection for three times, serum
      IL-2, IL-4 and IL-10 and whole brain IL-1beta level, hippocampal neuronal
      apoptosis level were measured. The cognitive ability in rats was tested by water
      maze. RESULTS: Water maze test showed on the 1st d, the maze test latency of the
      control group, the experimental group B and the experimental group C water were
      decreased gradually; Compared with the control group after 3 days, the latency of
      the experimental group A, experimental group B and experimental group C were all
      decreased, the crossing circle times were also reduced. Hippocampal neuron
      apoptosis were (2.3 +/- 1.7)%, (14.7 +/- 6.9)%, (4.2 +/- 3.3)%, (10.2 +/- 4.8)%
      in control group, experimental group A, experimental group B and experimental
      group C, respectively. The neurons apoptosis of experimental group A was
      significantly increased. The serum IL-4 and IL-10 of the experimental group A,
      experimental group B and experimental group C after anesthesia were significantly
      higher than the control group. The whole brain IL-1beta of the experimental group
      A, experimental group B and experimental group C were significantly lower than
      the control group. CONCLUSIONS: Propofol can reduce anesthesia effect of ketamine
      on the cognitive function and immune function in the young rats.

PMID- 25063073
TI  - Expression and function of CXCR2, CXCR7 of acute leukemic cells in rat.
AB  - OBJECTIVE: To investigate the expression and function of chemokine receptor CXCR2
      and CXCR7 in the rat with acute leukemia. METHODS: Flow cytometry and RT-PCR were
      used to detect the CXCR2, CXCR7 expression on the bone marrow cell surface of the
      acute leukemia group and the control group. RESULTS: The bone marrow cell surface
      CXCR2, CXCR7 relative fluorescence intensity of the observation group was
      significantly higher than the control group (P<0.05). The CXCR7 expression of the
      extramedullary infiltration group was significantly higher than non
      extramedullary infiltration group (P<0.05). The CXCR2, CXCR7mRNA median
      expression level of the observation group was higher than the control group. The
      CXCR2 expression and CXCR7 expression of the observation group was positively
      correlated, and the correlation coefficient was 0.782 (P<0.01). CONCLUSIONS: The
      chemokine receptor CXCR2 and CXCR7 are highly expressed in acute leukemia, which
      may be associated with the occurrence of leukemia.

PMID- 25063075
TI  - Osteoprotegerin is not a determinant of metabolic syndrome in sub-Saharan
      Africans after age adjustment.
AB  - OBJECTIVES: Osteoprotegerin (OPG), a soluble member of tumor necrosis factor
      receptor superfamily that inhibits bone resorption, has been suggested as a
      cardiovascular risk factor in humans. In this study, we aim to investigate the
      potential relationship between OPG and MetS (MetS) in a sub-Saharan African
      population. METHODS: Four hundred and eleven volunteers (152 men, 259 women) aged
      >=18 years recruited from the general population in Douala and Edea, Cameroon
      participated in this study. Anthropometric parameters measured and blood samples
      were collected for glucose, serum lipids and OPG concentrations measurements.
      Mean differences of the variables in different groups were compared using
      Students' t test. We performed logistic regressions to analyze the impact of
      independent factors on the relation between OPG and MetS outcome. MetS was
      defined using the Joint Interim Statement 2009. RESULTS: OPG levels did not vary
      significantly between both men and women with and without MetS (both P>0.05).
      However, with high fasting blood glucose (>=5.6 mmol/L) had a significantly
      higher OPG level than those with lower glucose level (P=0.014). In multiple
      logistic regression analysis, MetS did not show any significant association with
      serum OPG levels in men and women after adjusting for age, physical activity,
      alcohol consumption and menopausal status in women (P=0.720 and P=0.930
      respectively). CONCLUSION: This study failed to demonstrate any relationship
      between OPG and MetS. Nevertheless, the positive association between blood
      glucose and OPG levels reveals that OPG might be involved in cardiovascular risk
      development in this sub-Saharan African population.

PMID- 25063077
TI  - Enhanced cellular uptake and gene silencing activity of siRNA molecules mediated
      by chitosan-derivative nanocomplexes.
AB  - The RNA interference (RNAi) constitutes a conservative mechanism in eukaryotic
      cells that induces silencing of target genes. In mammalians, the RNAi is
      triggered by siRNA (small interfering RNA) molecules. Due to its potential in
      silencing specific genes, the siRNA has been considered a potential alternative
      for the treatment of genetic and acquired diseases. However, the siRNA therapy
      has been limited by its low stability and rapid degradation in presence of
      nucleases, low cellular uptake, and immune response activation. In order to
      overcome these drawbacks, we propose the synthesis and characterization of non
      viral delivery systems using chitosan derivatives to obtain siRNA complexes
      (polyplexes). The non-viral delivery systems synthesized included PEG-g-OCs
      (oligochitosan) and PEG-g-Cs (chitosan medium molecular weight). Both systems
      allowed the formation of siRNA polyplexes, increased the stability of siRNA in
      the presence of nucleases, enhanced cellular internalization, and showed low
      toxicity in the A549 cell line. Finally, the complexes obtained with the PEG-g
      OCs system showed silencing activity in a GFP model in the cell line A549 in
      comparison with naked siRNA. 

PMID- 25063076
TI  - Inhibitors of histone deacetylases enhance neurotoxicity of DNA damage.
AB  - The nonselective inhibitors of class I/II histone deacetylases (HDACs) including
      trichostatin A and the clinically used suberoylanilide hydroxamic acid (SAHA,
      vorinostat) are neuroprotective in several models of neuronal injury. Here, we
      report that in cultured cortical neurons from newborn rats and in the cerebral
      cortex of whole neonate rats, these HDAC inhibitors exacerbated cytotoxicity of
      the DNA double-strand break (DSB)-inducing anticancer drug etoposide by enhancing
      apoptosis. Similar neurotoxic interactions were also observed in neurons that
      were treated with other DNA damaging drugs including cisplatin and camptothecin.
      In addition, in rat neonates, SAHA increased cortical neuron apoptosis that was
      induced by a single injection of the NMDA receptor antagonist dizocilpine
      (MK801). In etoposide-treated neurons, the nonselective HDAC inhibition resulted
      in more DSBs. It also potentiated etoposide-induced accumulation and
      phosphorylation of the pro-apoptotic transcription factor p53. Moreover,
      nonselective HDAC inhibition exacerbated neuronal apoptosis that was induced by
      the overexpressed p53. Importantly, such effects cannot be fully explained by
      inhibition of HDAC1, which is known to play a role in DSB repair and regulation
      of p53. The specific HDAC1 inhibitor MS275 only moderately enhanced etoposide
      induced neuronal death. Although in etoposide-treated neurons MS275 increased
      DSBs, it did not affect activation of p53. Our findings suggest that besides
      HDAC1, there are other class I/II HDACs that participate in neuronal DNA damage
      response attenuating neurotoxic consequences of genotoxic insults to the
      developing brain. 

PMID- 25063078
TI  - Culturomics and pyrosequencing evidence of the reduction in gut microbiota
      diversity in patients with broad-spectrum antibiotics.
AB  - The human gut flora is currently widely characterised using molecular techniques.
      Microbial culturomics (large-scale culture conditions with identification of
      colonies using MALDI-TOF or 16S rRNA) is part of the rebirth of bacterial culture
      that was initiated by environmental microbiologists for the design of axenic
      culture for intracellular bacteria in clinical microbiology. Culturomics was
      performed on four stool samples from patients treated with large-scale
      antibiotics to assess the diversity of their gut flora in comparison with other
      culture-dependent studies. Pyrosequencing of the V6 region was also performed and
      was compared with a control group. Gut richness was also estimated by bacterial
      counting after microscopic observation. In total, 77 culture conditions were
      tested and 32,000 different colonies were generated; 190 bacterial species were
      identified, with 9 species that had not been isolated from the human gut before
      this study, 7 newly described in humans and 8 completely new species. A dramatic
      reduction in diversity was observed for two of the four stool samples for which
      antibiotic treatment was prolonged and uninterrupted. The total number of
      bacteria was generally preserved, suggesting that the original population was
      replaced but was sustained in size. Discordances between culture and
      pyrosequencing biodiversity biomarkers highlight the depth of bias of molecular
      studies. Stool samples studied showed a dramatic reduction in bacterial
      diversity. Considering the variable antibiotic concentration in the gut, this
      reduction in the number of species is possibly linked to the production of
      bacteriocin in the upper digestive tract by specific bacteria, such as
      Lactobacillus spp. 

PMID- 25063079
TI  - Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic
      Processing in the SAMP8 Mouse.
AB  - The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging,
      displays many established pathological features of Alzheimer's disease. Cognitive
      impairments and increased levels of hyperphosphorylated tau are found in the
      hippocampus of SAMP8 mice along with an increased beta-secretase activity and
      amyloid-beta (Abeta) depositions that increase in number and extent with age.
      Based on a previous study from our laboratory showing an amelioration of
      cognitive impairments and tau pathology by sildenafil, in this study we tested
      whether this drug could also modulate the amyloid precursor protein amyloidogenic
      processing in this mouse model. Our results show that the protein levels of the
      beta-secretases beta-site amyloid precursor protein cleaving enzyme 1 and
      cathepsin B are higher in the hippocampus of 9-month-old SAMP8 mice than those of
      age-matched senescence-resistant-1. Sildenafil (7.5mg/kg for 4 weeks) attenuated
      learning and memory impairments shown by SAMP8 mice in the passive avoidance
      test. The increased expression of beta-site amyloid precursor protein cleaving
      enzyme 1 was also reduced by sildenafil, an effect paralleled to decreases in the
      activities of two beta-site amyloid precursor protein cleaving enzyme 1
      modulators, calpain and cyclin-dependent kinase 5 protein. Interestingly,
      sildenafil enhanced both Akt and glycogen synthase kinase-3beta (ser9)
      phosphorylation, which could be mediating the reduction in cathepsin B levels
      found in the hippocampus of sildenafil-treated SAMP8 mice. Sildenafil-induced
      reduction in beta-site amyloid precursor protein cleaving enzyme 1 and cathepsin
      B expression in SAMP8 mice was associated with a decrease in hippocampal Abeta42
      levels which, in turn, could mediate the parallel decline in glial fibrillary
      acidic protein expression observed in these animals. These findings highlight the
      therapeutic potential of sildenafil in Alzheimer's disease pathogenesis. 

PMID- 25063080
TI  - Knee osteoarthritis and frailty: findings from the Multicenter Osteoarthritis
      Study and Osteoarthritis Initiative.
AB  - BACKGROUND: Knee osteoarthritis (OA) and frailty are two conditions that are
      associated with functional limitation and disability in elders, yet their
      relation to one another is not known. METHODS: We included participants from two
      large, multicenter studies enriched with community dwelling older adults with
      knee OA (Multicenter Osteoarthritis Study and Osteoarthritis Initiative). Knee OA
      was defined radiographically (ROA) and symptomatically (SOA). Frailty was defined
      using the Study of Osteoporotic Fracture index as the presence of >=2 of the
      following: (i) weight loss >5% between two consecutive visits; (ii) inability to
      arise from chair five times without support; (iii) poor energy. Cross-sectional
      and longitudinal associations of knee OA with prevalent and incident frailty,
      respectively, were examined using binomial regression with robust variance
      estimation, adjusting for potential confounders. RESULTS: In the cross-sectional
      analyses, frailty was more prevalent among participants with ROA (4.39% vs 2.77%;
      PR 1.60 [1.07, 2.39]) and SOA (5.88% vs 2.79%; PR 1.92 [1. 35, 2.74]) compared
      with those without ROA or SOA, respectively. In the longitudinal analyses, risk
      of developing frailty was greater among those with ROA (4.73% vs 2.50%; RR 1.45
      [0.91, 2.30]) and SOA (6.30% vs 2.83%; RR 1.66 [1.11, 2.48]) than those without
      ROA or SOA, respectively. CONCLUSIONS: Knee OA is associated with greater
      prevalence and risk of developing frailty. Understanding the mechanisms linking
      these two common conditions of older adults would aid in identifying novel
      targets for treatment or prevention of frailty.

PMID- 25063081
TI  - B12 deficiency increases with age in hospitalized patients: a study on 14,904
      samples.
AB  - BACKGROUND: Cobalamin deficiency is responsible for hematological, neurological,
      neurocognitive, and neuropsychiatric impairments and is a risk factor for
      cardiovascular diseases, particularly in the elderly people. METHODS: In order to
      determine B12 status in old inpatients, a total number of 14,904 hospitalized
      patients in whom B12 measurements were performed in five hospitals in the Paris
      metropolitan area were included from January 1, 2011 to December 31, 2011. The
      aims of the study were to determine whether age had an impact on B12 and folate
      deficiencies and to evaluate correlations between B12 and biological parameters
      folate, hemoglobin, mean cell volume, homocystein (tHcy)-and age. RESULTS:
      Patients were aged 70.3+/-19.5 years. Low B12 concentration (<200ng/L) was
      observed in 4.6% of cases, 24.2% had middle B12 concentration (200-350ng/L),
      12.6% were functional B12 deficient (B12 < 350 ng/L associated to high tHcy
      level, tHcy > 17 umol/L), 20.4% had low folate concentration (folate < 4 ug/L),
      10.6% were functional folate deficient (folate < 4 ug/L associated to tHcy > 17
      umol/L), and 4.7% of patients were both functional B12 and folate deficient. The
      B12 or folate deficient patients had lower mean cell volume level than
      nondeficient patients. Increase in mean cell volume and tHcy concentrations with
      age and decrease in B12, folate, and hemoglobin levels with age were observed.
      Frequency of functional B12 deficiency was 9.6% in patients aged 30-60 years and
      14.2% in patients over 90 years. Frequency of functional folate deficiency was
      9.5% in 30-60 years and 12.1% in >90 years. CONCLUSIONS: In inpatients,
      functional B12 deficiency and functional folate deficiency increase with age and
      are not associated with anemia or macrocytosis. False vitamin B deficiencies are
      frequent.

PMID- 25063082
TI  - Developing a utility index for the Aberrant Behavior Checklist (ABC-C) for
      fragile X syndrome.
AB  - PURPOSE: This study aimed to develop a utility index (the ABC-UI) from the
      Aberrant Behavior Checklist-Community (ABC-C), for use in quantifying the benefit
      of emerging treatments for fragile X syndrome (FXS). METHODS: The ABC-C is a
      proxy-completed assessment of behaviour and is a widely used measure in FXS. A
      subset of ABC-C items across seven dimensions was identified to include in health
      state descriptions. This item reduction process was based on item performance,
      factor analysis and Rasch analysis performed on an observational study dataset,
      and consultation with five clinical experts and a methodological expert.
      Dimensions were combined into health states using an orthogonal design and valued
      using time trade-off (TTO), with lead-time TTO methods used where TTO indicated a
      state valued as worse than dead. Preference weights were estimated using mean,
      individual level, ordinary least squares and random-effects maximum likelihood
      estimation [RE (MLE)] regression models. RESULTS: A representative sample of the
      UK general public (n = 349; mean age 35.8 years, 58.2% female) each valued 12
      health states. Mean observed values ranged from 0.92 to 0.16 for best to worst
      health states. The RE (MLE) model performed best based on number of significant
      coefficients and mean absolute error of 0.018. Mean utilities predicted by the
      model covered a similar range to that observed. CONCLUSIONS: The ABC-UI estimates
      a wide range of utilities from patient-level FXS ABC-C data, allowing estimation
      of FXS health-related quality of life impact for economic evaluation from an
      established FXS clinical trial instrument.

PMID- 25063083
TI  - Intimate partner violence and health-related quality of life in European men and
      women: findings from the DOVE study.
AB  - PURPOSE: Little is known on the specific relation between being a perpetrator or
      both a victim and perpetrator of intimate partner violence (IPV) and health
      related quality of life (HRQoL). We assessed the association between HRQoL and
      abuse, considering men and women as victims, perpetrators or reciprocally.
      METHODS: Participants were adult men and women (n = 3,496), randomly selected
      from the general population of six European cities. The Revised-Conflict-Tactics
      Scales and the Medical-Outcomes-Study 36-item Short-Form Health Survey (SF-36)
      were used to measure IPV and HRQoL. The age-, education-, and city-adjusted mean
      scores[standard error] of the physical and of the mental SF-36 component
      summaries were used to compare victims-only, perpetrators-only, and those
      involved in both (bidirectional or reciprocal cases) with those not involved in
      past-year and lifetime physical assault and/or sexual coercion. RESULTS: The
      physical component summary was significantly lower in women involved in past-year
      bidirectional physical assault compared with non-abused women. The mental
      component summary in women not involved in IPV was significantly higher than in
      those physically abused, regardless of type of involvement. Women victims-only of
      past-year sexual coercion and victims or involved in bidirectional concomitant
      physical and sexual IPV also presented lower scores in the mental component
      summary than women not involved in IPV. In men, significantly lower scores in the
      mental component summary were found in the past-year bidirectional physically
      assaulted group and among those involved bidirectionally in both physical and
      sexual IPV compared with men not involved in IPV. CONCLUSION: Experiencing
      physical and sexual IPV is negatively associated with HRQoL. Lower scores in the
      mental component summary of the SF-36 are evident among female victims and among
      males and females involved in intimate partner violence as both victims and
      perpetrators when compared to females and males not involved in violence.

PMID- 25063084
TI  - Mechanical properties of a new thermoplastic polymer orthodontic archwire.
AB  - A new thermoplastic polymer for orthodontic applications was obtained and
      extruded into wires with round and rectangular cross sections. We evaluated the
      potential of new aesthetic archwire: tensile, three point bending, friction and
      stress relaxation behaviour, and formability characteristics were assessed.
      Stresses delivered were generally slightly lower than typical beta-titanium and
      nickel-titanium archwires. The polymer wire has good instantaneous mechanical
      properties; tensile stress decayed about 2% over 2h depending on the initial
      stress relaxation for up to 120h. High formability allowed shape bending similar
      to that associated with stainless steel wires. The friction coefficients were
      lower than the metallic conventional archwires improving the slipping with the
      brackets. This new polymer could be a good candidate for aesthetic orthodontic
      archwires. 

PMID- 25063085
TI  - Anti-wear properties of the molluscan shell Scapharca subcrenata: influence of
      surface morphology, structure and organic material on the elementary wear
      process.
AB  - As a typical natural biological mineralisation material, molluscan shells have
      excellent wear-resistance properties that result from the interactions amongst
      biological coupling elements such as morphology, structure and material. The in
      depth study of the wear-resistance performance of shells and the contribution
      made by each coupling element may help to promote the development of new bionic
      wear-resistant devices. The objective of this study was to investigate the
      influence of surface morphology (rib distribution on the shell), structure (rib
      coupled with nodules) and material (organic matter) on the anti-wear performance
      of the molluscan Scapharca subcrenata shell. The effect and contribution of each
      of these biological coupling elements were systematically investigated using the
      comparative experiment method. All three were found to exert significant effects
      on the shell's wear-resistance ability, and their individual contributions to
      that ability were revealed. Organic material can be classified as the principal
      coupling element, rib morphology as the secondary coupling element and the
      combined rib-nodule structure as the general coupling element. 

PMID- 25063086
TI  - Higher number of pentosidine cross-links induced by ribose does not alter tissue
      stiffness of cancellous bone.
AB  - The role of mature collagen cross-links, pentosidine (Pen) cross-links in
      particular, in the micromechanical properties of cancellous bone is unknown. The
      aim of this study was to examine nonenzymatic glycation effects on tissue
      stiffness of demineralized and non-demineralized cancellous bone. A total of 60
      bone samples were derived from mandibular condyles of six pigs, and assigned to
      either control or experimental groups. Experimental handling included incubation
      in phosphate buffered saline alone or with 0.2M ribose at 37 degrees C for 15
      days and, in some of the samples, subsequent complete demineralization of the
      sample surface using 8% EDTA. Before and after experimental handling, bone
      microarchitecture and tissue mineral density were examined by means of
      microcomputed tomography. After experimental handling, the collagen content and
      the number of Pen, hydroxylysylpyridinoline (HP), and lysylpyridinoline (LP)
      cross-links were estimated using HPLC, and tissue stiffness was assessed by means
      of nanoindentation. Ribose treatment caused an up to 300-fold increase in the
      number of Pen cross-links compared to nonribose-incubated controls, but did not
      affect the number of HP and LP cross-links. This increase in the number of Pen
      cross-links had no influence on tissue stiffness of both demineralized and
      nondemineralized bone samples. These findings suggest that Pen cross-links do not
      play a significant role in bone tissue stiffness.

PMID- 25063087
TI  - Preparation and antibacterial property of silver-containing mesoporous 58S
      bioactive glass.
AB  - The modified mesoporous 58S bioglass (SM58S) was prepared through surface
      modification of the mesoporous 58S bioglass (M58S) with gamma-aminopropyl
      triethoxysilane (KH550). The results of Fourier transform infrared spectroscopy
      (FTIR) and thermogravimetric analysis (TGA) showed that the amino groups were
      grafted to the surface of M58S after modification with KH550. The silver
      containing SM58S (Ag-SM58S) and M58S (Ag-M58S) were prepared by the dipping
      method. The Ag(+) loading capacity, release rate and antibacterial properties of
      Ag-SM58S and Ag-M58S were investigated. It is indicated that surface modification
      of M58S with KH550 can improve the Ag(+) loading capacity. The result of
      antibacterial property showed that Ag-SM58S exhibited significant anti-bacterial
      effects against Escherichia coli and Staphylococcus aureus. The sustained release
      of Ag(+) from Ag-SM58S for 768h ensured excellent antibacterial property of Ag
      SM58S. In vitro osteoblast proliferation and differentiation tests showed that Ag
      SM58S was a good matrix for the growth of osteoblasts. Consequently, the results
      of the study suggested that Ag-SM58S might be a promising bone repair material.

PMID- 25063088
TI  - Synthesis of polyethylenimine (PEI) functionalized silver nanoparticles by a
      hydrothermal method and their antibacterial activity study.
AB  - In this study, we report a facile, one-step hydrothermal method to synthesize PEI
      functionalized Ag nanoparticles in which no extra reducing agent is needed and
      PEI serves as a reducing agent and a stabilizing agent. The obtained Ag colloids
      have been characterized by TEM, UV absorption spectra and laser particle size
      analyzer. We found that the size of Ag nanoparticles can be tuned through the
      alteration of the temperature and growth mode. Under an acidic condition, PEI
      functionalized Ag nanoparticles are positively charged. More importantly, the Ag
      colloids exhibited stronger antibacterial activity in the bactericidal test. Its
      bactericidal efficiency exceeds the commonly used antibacterial agents such as
      Erythromycin, chloramphenicol and penicillin as well as AgNO3 solution. These
      results prove that our synthesis method is very efficient to produce a stable PEI
      functionalized Ag colloid with excellent antibacterial activity. 

PMID- 25063089
TI  - Simultaneous determination of mycophenolate mofetil and its active metabolite,
      mycophenolic acid, by differential pulse voltammetry using multi-walled carbon
      nanotubes modified glassy carbon electrode.
AB  - A highly sensitive electrochemical sensor for the simultaneous determination of
      mycophenolate mofetil (MPM) and mycophenolic acid (MPA) was fabricated by multi
      walled carbon nanotubes modified glassy carbon electrode (MWCNTs/GCE). The
      electrochemical behavior of these two drugs was studied at the modified electrode
      using cyclic voltammetry and adsorptive differential pulse voltammetry. MPM and
      MPA were oxidized at the GCE during an irreversible process. DPV analysis showed
      two oxidation peaks at 0.87V and 1.1V vs. Ag/AgCl for MPM and an oxidation peak
      at 0.87V vs. Ag/AgCl for MPA in phosphate buffer solution of pH5.0. The
      MWCNTs/GCE displayed excellent electrochemical activities toward oxidation of MPM
      and MPA relative to the bare GCE. The experimental design algorithm was used for
      optimization of DPV parameters. The electrode represents linear responses in the
      range 5.0*10(-6) to 1.6*10(-4)molL(-1) and 2.5*10(-6)molL(-1) to 6.0*10(-5)molL(
      1) for MPM and MPA, respectively. The detection limit was found to be 9.0*10(
      7)molL(-1) and 4.0*10(-7)molL(-1) for MPM and MPA, respectively. The modified
      electrode showed a good sensitivity and stability. It was successfully applied to
      the simultaneous determination of MPM and MPA in plasma and urine samples.

PMID- 25063090
TI  - Correction for porous scaffold structure design.

PMID- 25063091
TI  - Deformation behavior of human dentin in liquid nitrogen: a diametral compression
      test.
AB  - Contribution of the collagen fibers into the plasticity of human dentin is
      considered. Mechanical testing of dentin at low temperature allows excluding the
      plastic response of its organic matrix. Therefore, deformation and fracture
      behavior of the dentin samples under diametral compression at room temperature
      and liquid nitrogen temperature are compared. At 77K dentin behaves like almost
      brittle material: it is deformed exclusively in the elastic regime and it fails
      due to growth of the sole crack. On the contrary, dentin demonstrates the ductile
      response at 300K. There are both elastic and plastic contributions in the
      deformation of dentin samples. Multiple cracking and crack tip blunting precede
      the failure of samples. Organic phase plays an important role in fracture of
      dentin: plasticity of the collagen fibers could inhibit the crack growth. 

PMID- 25063092
TI  - Effect of spatial confinement on magnetic hyperthermia via dipolar interactions
      in Fe3O4 nanoparticles for biomedical applications.
AB  - In this work, the effect of nanoparticle confinement on the magnetic relaxation
      of iron oxide (Fe3O4) nanoparticles (NP) was investigated by measuring the
      hyperthermia heating behavior in high frequency alternating magnetic field. Three
      different Fe3O4 nanoparticle systems having distinct nanoparticle configurations
      were studied in terms of magnetic hyperthermia heating rate and DC magnetization.
      All magnetic nanoparticle (MNP) systems were constructed using equivalent ~10nm
      diameter NP that were structured differently in terms of configuration, physical
      confinement, and interparticle spacing. The spatial confinement was achieved by
      embedding the Fe3O4 nanoparticles in the matrices of the polystyrene spheres of
      100 nm, while the unconfined was the free Fe3O4 nanoparticles well-dispersed in
      the liquid via PAA surface coating. Assuming the identical core MNPs in each
      system, the heating behavior was analyzed in terms of particle freedom (or
      confinement), interparticle spacing, and magnetic coupling (or dipole-dipole
      interaction). DC magnetization data were correlated to the heating behavior with
      different material properties. Analysis of DC magnetization measurements showed
      deviation from classical Langevin behavior near saturation due to dipole
      interaction modification of the MNPs resulting in a high magnetic anisotropy. It
      was found that the Specific Absorption Rate (SAR) of the unconfined nanoparticle
      systems were significantly higher than those of confined (the MNPs embedded in
      the polystyrene matrix). This increase of SAR was found to be attributable to
      high Neel relaxation rate and hysteresis loss of the unconfined MNPs. It was also
      found that the dipole-dipole interactions can significantly reduce the global
      magnetic response of the MNPs and thereby decrease the SAR of the nanoparticle
      systems.

PMID- 25063093
TI  - 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on
      keratinocytes against reactive oxygen species by insect virus-derived protein
      microcrystals.
AB  - Stable protein microcrystals called polyhedra are produced by certain insect
      viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized
      within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of
      keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7
      polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture
      and melanin was also typically observed in the lower layer. The 3D cell culture
      model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis
      due to effective melanogenesis, proliferation and differentiation of
      keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when
      keratinocytes were treated with menadione, which is a generator of reactive
      oxygen species. The cytoprotective effect was activated by the inositol
      triphosphate kinase-Akt pathway leading to upregulation of the antioxidant
      enzymes superoxide dismutase and peroxiredoxin 6.

PMID- 25063094
TI  - Gold nanoparticles stimulate differentiation and mineralization of primary
      osteoblasts through the ERK/MAPK signaling pathway.
AB  - Gold nanoparticles (AuNPs) have shown great promise for a variety of
      applications, including chemistry, biology, and medicine. Recently, AuNPs have
      found promising applications in cartilage and bone repair. However, to realize
      the above promised applications, more work needs to be carried out to clarify the
      interactions between biological systems and AuNPs. In the present study, primary
      osteoblasts were used to evaluate the biocompatibility of 20-nm and 40-nm AuNPs,
      including morphology, proliferation, differentiation, gene and protein
      expression, and the underlying mechanisms. The results demonstrated that AuNPs
      were taken up by osteoblasts and aggregated in perinuclear compartment and
      vescular structures, but no morphological changes were observed. AuNPs could
      significantly promote the proliferation of osteoblasts, enhance the ALP
      activities, and increase the number of bone nodules and calcium content in vitro.
      In addition, the expression of BMP-2, Runx-2, OCN and Col-1 was remarkably up
      regulated in the presence of AuNPs. It is noteworthy that 20-nm AuNPs are more
      potent than 40-nm AuNPs in regulating osteoblast activities. Besides, AuNPs
      increased the level of ERK phosphorylation/total ERK, suggesting the activation
      of ERK/MAPK pathway is involved in above activities. In conclusion, AuNPs
      exhibited great biocompatibility with osteoblasts, and have tremendous potential
      to be used as drug and/or gene delivery carrier for bone and tissue engineering
      in the future. 

PMID- 25063095
TI  - Synthesis and characterization of Ce-substituted hydroxyapatite by sol-gel
      method.
AB  - Both undoped hydroxyapatite (HAp) and three Ce-substituted HAp samples with
      variable amounts (from 0.5 to 2 at.%) of Ce were synthesized by sol-gel method.
      The samples were studied by X-ray diffraction (XRD), Fourier transform infrared
      (FTIR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X
      ray (EDX) spectroscopy to determine the crystallite size, crystallinity degree,
      phases, functional groups, morphology and elemental composition. In all samples,
      the amount of HAp exceeded 92%, while the amount of admixture beta-TCP was always
      below 8% and no changes were observed by addition of Ce. The crystallinity degree
      of the samples was always within 84-89%, while the calculated dimensions of
      crystallites appeared to be within 26-35nm. The microstructure and elemental
      composition of all the samples were found to be affected by the addition of Ce.

PMID- 25063096
TI  - Facile synthesis of both needle-like and spherical hydroxyapatite nanoparticles:
      effect of synthetic temperature and calcination on morphology, crystallite size
      and crystallinity.
AB  - Synthetic hydroxyapatite (HA) nanoparticles, that mimic natural HA, are widely
      used as biocompatible coatings on prostheses to repair and substitute human
      bones. In this study, HA nanoparticles are prepared by precipitating them from a
      precursor solution containing calcium sucrate and ammonium dihydrogen
      orthophosphate, at a Ca/P mole ratio of 1.67:1, at temperatures, ranging from 10
      degrees C to 95 degrees C. A set of products, prepared at different temperatures,
      is analyzed for their crystallinity, crystallite size, morphology, thermal
      stability and composition, by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), thermogravimetric analysis (TGA) and Fourier transform infrared
      (FT-IR) spectroscopic techniques, while the other set is analyzed after calcining
      the respective products, soon after their synthesis, for 3h, at 700 degrees C.
      The as-prepared products, after 2h of drying, without any calcination, are not
      crystalline, but they grow very slowly into needle-like morphologies, as they are
      ripened with time. The percentage crystallinity of the final products increases
      from 15% to 52%, with increasing the preparative temperature. The calcined
      samples always produce spherical nanoparticles of essentially the same diameter,
      between 90 nm and 100 nm, which does not change due to aging and preparative
      temperatures. Therefore, the same method can be utilized to synthesize both
      spherical and needle-like nanoparticles of hydroxyapatite, with well-defined
      sizes and shapes. The ability to use readily available cheap raw materials, for
      the synthesis of such well-defined crystallites of hydroxyapatite, is an added
      advantage of this method, which may be explored further for the scaling up of the
      procedures to suit to industrial scale synthesis of such hydroxyapatite
      nanoparticles.

PMID- 25063097
TI  - In vitro investigation of biodegradable polymeric coating for corrosion
      resistance of Mg-6Zn-Ca alloy in simulated body fluid.
AB  - A silane-based biodegradable coating was developed and investigated to improve
      corrosion resistance of an Mg-6Zn-Ca magnesium alloy to delay the biodegradation
      of the alloy in the physiological environment. Conditions were optimized to
      develop a stable and uniform hydroxide layer on the alloys surface-known to
      facilitate silane-substrate adhesion. A composite coating of two silanes, namely,
      diethylphosphatoethyltriethoxysilane (DEPETES) and bis-[3-(triethoxysilyl)
      propyl] tetrasulfide (BTESPT), was developed, by the sol-gel route. Corrosion
      resistance of the coated alloy was characterized in a modified-simulated body
      fluid (m-SBF), using potentiodynamic polarization and electrochemical impedance
      spectroscopy (EIS). The silane coating provided significant and durable corrosion
      resistance. During the course of this, hydrogen evolution and pH variation, if
      any, were monitored for both bare and coated alloys. The coating morphology was
      characterized using scanning electron microscopy (SEM) and energy dispersive X
      ray analysis (EDAX) and the cross-linking in the coating was studied using
      Fourier transform infrared spectroscopy (FTIR). As indicated by X-ray diffraction
      (XRD) results, an important finding was the presence of hydrated magnesium
      phosphate on the sample that was subjected to immersion in m-SBF for 216h.
      Magnesium phosphate is reported to support osteoblast formation and tissue
      healing.

PMID- 25063098
TI  - A novel bio-safe phase separation process for preparing open-pore biodegradable
      polycaprolactone microparticles.
AB  - Open-pore biodegradable microparticles are object of considerable interest for
      biomedical applications, particularly as cell and drug delivery carriers in
      tissue engineering and health care treatments. Furthermore, the engineering of
      microparticles with well definite size distribution and pore architecture by bio
      safe fabrication routes is crucial to avoid the use of toxic compounds
      potentially harmful to cells and biological tissues. To achieve this important
      issue, in the present study a straightforward and bio-safe approach for
      fabricating porous biodegradable microparticles with controlled morphological and
      structural features down to the nanometer scale is developed. In particular,
      ethyl lactate is used as a non-toxic solvent for polycaprolactone particles
      fabrication via a thermal induced phase separation technique. The used approach
      allows achieving open-pore particles with mean particle size in the 150-250 MUm
      range and a 3.5-7.9 m(2)/g specific surface area. Finally, the combination of
      thermal induced phase separation and porogen leaching techniques is employed for
      the first time to obtain multi-scaled porous microparticles with large external
      and internal pore sizes and potential improved characteristics for cell culture
      and tissue engineering. Samples were characterized to assess their thermal
      properties, morphology and crystalline structure features and textural
      properties.

PMID- 25063099
TI  - Synthesis of methylprednisolone loaded ibuprofen modified inulin based
      nanoparticles and their application for drug delivery.
AB  - Ibuprofen modified inulin was synthesized through a direct esterification linkage
      in which the in situ activation of the carboxylic acid with N,N'
      carbonyldiimidazole was carried out. The critical aggregation concentration of
      the ibuprofen modified inulin was determined by using pyrene as the fluorescence
      probe. Methylprednisolone loaded nanoparticles were prepared by the self-assembly
      of the ibuprofen modified inulin copolymer and methylprednisolone. In vitro
      release of the methylprednisolone and the cytotoxicity of the methylprednisolone
      loaded nanoparticles against RSC-96 cells were evaluated. Since the ibuprofen and
      methylprednisolone could stimulate a significant neurite growth and diminish the
      human neurological deficits after the spinal cord injury, the methylprednisolone
      loaded nanoparticles based on the ibuprofen modified inulin copolymer may have a
      great potential in the synergetic effect treatment for spinal cord injury. 

PMID- 25063100
TI  - In vitro and in vivo corrosion measurements of Mg-6Zn alloys in the bile.
AB  - Mg-6Zn alloy was studied as candidate biodegradable metallic implants for the
      common bile duct (CBD) in terms of its in vitro corrosion and in vivo corrosion.
      Electrochemical measurements, immersion tests and hydrogen evolution were
      performed in the bile and Hanks' solution to evaluate the in vitro degradation
      behavior of Mg-6Zn alloy. The results showed that the degradation rate and
      hydrogen evolution were higher when Mg-6Zn alloy immersed in the bile than in the
      Hanks' solution. The polarization resistance of the samples in the Hanks'
      solution was about 1.5 times to that in the bile. In the in vivo experiment, Mg
      6Zn alloy stents were inserted in CBD of 42 rabbits, and CT scans, the value of
      total bilirubin (TB) and in vivo corrosion rate were determined. From the results
      of CT images and the fluctuations of TB values, it can be seen that the stent was
      degraded gradually in CBD. After 1 week post-implantation, the majority of the Mg
      6Zn alloy sample remained in the CBD. Usually the required support time for CBD
      stent was approximately 7-10 days, thus the Mg-6Zn alloy stent was very close to
      the clinical requirement for CBD support materials. After three weeks, the
      residual weight of the Mg-6Zn alloy was only 9% of the original weight. The in
      vivo corrosion rate of Mg-6Zn alloy was ~0.107 mm.year(-1), which was much lower
      than that calculated in vitro (~0.72 mm.year(-1) by electrochemical test). Based
      on our research, there is promising for the Mg-6Zn alloy in CBD applications.

PMID- 25063101
TI  - Effect of Tris-acetate buffer on endotoxin removal from human-like collagen used
      biomaterials.
AB  - Protein preparation, which has active ingredients designated for the use of
      biomaterials and therapeutical protein, is obtained by genetic engineering, but
      products of genetic engineering are often contaminated by endotoxins. Because
      endotoxin is a ubiquitous and potent proinflammatory agent, endotoxin removal or
      depletion from protein is essential for researching any biomaterials. In this
      study, we have used Tris-acetate (TA) buffer of neutral pH value to evaluate
      endotoxins absorbed on the Pierce high-capacity endotoxin removal resin. The
      effects of TA buffer on pH, ionic strength, incubation time as well as human-like
      collagen (HLC) concentration on eliminating endotoxins are investigated. In the
      present experiments, we design an optimal method for TA buffer to remove
      endotoxin from recombinant collagen and use a chromogenic tachypleus amebocyte
      lysate (TAL) test kit to measure the endotoxin level of HLC. The present results
      show that, the endotoxins of HLC is dropped to 8.3EU/ml at 25 mM TA buffer
      (pH7.8) with 150 mM NaCl when setting incubation time at 6h, and HLC recovery is
      about 96%. Under this experimental condition, it is proved to exhibit high
      efficiencies of both endotoxin removal and collagen recovery. The structure of
      treated HLC was explored by Transmission Electron Microscopy (TEM), demonstrating
      that the property and structure of HLC treated by TA buffer are maintained.
      Compared to the most widely used endotoxin removal method, Triton X-114
      extraction, using TA buffer can obtain the non-toxic HLC without extra treatment
      for removing the toxic substances in Triton X-114. In addition, the present study
      aims at establishing a foundation for further work in laboratory animal science
      and providing a foundation for medical grade biomaterials.

PMID- 25063102
TI  - Fabrication and cytocompatibility of spherical magnesium ammonium phosphate
      granules.
AB  - Magnesium phosphate compounds, as for example struvite (MgNH4PO4.6H2O), have
      comparable characteristics to calcium phosphate bone substitutes, but degrade
      faster under physiological conditions. In the present work, we used a struvite
      forming calcium doped magnesium phosphate cement with the formulation
      Ca0.75Mg2.25(PO4)2 and an ammonium phosphate containing aqueous solution to
      produce round-shaped granules. For the fabrication of spherical granules, the
      cement paste was dispersed in a lipophilic liquid and stabilized by surfactants.
      The granules were characterized with respect to morphology, size distribution,
      phase composition, compressive strength, biocompatibility and solubility. In
      general, it was seen that small granules can hardly be produced by means of
      emulsification, when the raw material is a hydraulic paste, because long setting
      times promote coalescence of initially small unhardened cement droplets. Here,
      this problem was solved by using an aqueous solution containing both the
      secondary (NH4)2HPO4 and primary ammonium phosphates NH4H2PO4 to accelerate the
      setting reaction. This resulted in granules with 97 wt.% having a size in the
      range between 200 and 1,000 MUm. The novel solution composition doubled the
      compressive strength of the cement to 37 +/- 5 MPa without affecting either the
      conversion to struvite or the cytocompatibility using human fetal osteoblasts.

PMID- 25063103
TI  - A novel one-pot process for near-net-shape fabrication of open-porous resorbable
      hydroxyapatite/protein composites and in vivo assessment.
AB  - We present a mild one-pot freeze gelation process for fabricating near-net,
      complex-shaped hydroxyapatite scaffolds and to directly incorporate active
      proteins during scaffold processing. In particular, the direct protein
      incorporation enables a simultaneous adjustment and control of scaffold
      microstructure, porosity, resorbability and enhancement of initial mechanical and
      handling stability. Two proteins, serum albumin and lysozyme, are selected and
      their effect on scaffold stability and microstructure investigated by biaxial
      strength tests, electron microscopy, and mercury intrusion porosimetry. The
      resulting hydroxyapatite/protein composites feature adjustable porosities from
      50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that
      of human spongiosa without any sintering step. Scaffold degradation behaviour and
      protein release are assessed by in vitro studies. A preliminary in vivo
      assessment of scaffold biocompatibility and resorption behaviour in adult
      domestic pigs is discussed. After implantation, composites were resorbed up to
      50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone
      formation after 4 weeks and 37% after 8 weeks were detected. All these
      investigations demonstrate the outstanding suitability of the one-pot-process to
      create, in a customisable and reliable way, biocompatible scaffolds with
      sufficient mechanical strength for handling and surgical insertion, and for
      potential use as biodegradable bone substitutes and versatile platform for local
      drug delivery.

PMID- 25063104
TI  - Porous hydrogel of wool keratin prepared by a novel method: an extraction with
      guanidine/2-mercaptoethanol solution followed by a dialysis.
AB  - In this study, we show a novel simple method to prepare a sponge-like porous
      keratin hydrogel through the extraction of wool keratin in a solution containing
      guanidine hydrochloride and 2-mercaptoethanol followed by dialysis for both
      aggregation of keratin and recrosslink. The gel had a highly porous structure and
      a fast-swelling property in rehydration after freeze-drying. It had also high
      mechanical strength both in the tensile test and the measurement of dynamic
      viscoelasticity. Three types of animal cells, PC12 cells, HOS cells and murine
      embryonic fibroblasts, well attached and grew on the surface of the porous
      hydrogel. 

PMID- 25063105
TI  - Application of enzyme/zeolite sensor for urea analysis in serum.
AB  - Urea biosensor based on zeolite-adsorbed urease was applied for analysis of blood
      serum samples. It should be noted, that this biosensor has a number of
      advantages, such as simple and fast performance, the absence of toxic compounds
      during biosensor preparation, high reproducibility and repeatability (RSD=9% and
      4%, respectively). The linear range of urea determination by using the biosensor
      was 0.003-0.75 mM, and the limit of urea detection was 3 MUM. The method of
      standard addition was used for analysis of serum samples with 500-fold dilution.
      Total time of analysis was 10 min. Good reproducibility of urea determination in
      real samples was demonstrated (RSD=10%). Biosensor results were verified by using
      a common method of urea determination (diacetyl monoxime reaction). It was shown
      that by using this biosensor distinguishing healthy people from people with renal
      dysfunction becomes easier.

PMID- 25063106
TI  - Synthesis and characterization of hybrid silica/PMMA nanoparticles and their use
      as filler in dental composites.
AB  - The effect of hybrid silica/poly(methylmethacrylate) (PMMA) nanoparticles on the
      properties of composites for dental restoration was evaluated. Hybrid
      nanoparticles with silica as core and PMMA as shell were obtained by a seeded
      emulsion polymerization process. Fourier transform infrared spectrum of the
      hybrid nanoparticles shows an intense peak at 1,730 cm(-1), corresponding to
      carbonyl groups (CO) of the ester. The thermal stability of the hybrid particles
      decreases with increasing amounts of PMMA and the residual mass at 700 degrees C
      corresponds to the silica content in the hybrid particles. Composites were
      obtained by dispersing nanoparticles (silica or hybrid), as fillers, in a resin
      bis glycidyl dimethacrylate (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA)
      (40%/60% (w/w)). The paste was then placed in a mold and polymerized under light
      irradiation. During the preparation of the composites, with the hybrid
      nanoparticles, the monomers swell the PMMA shell and after photo-curing, a semi
      interpenetrating network (semi-IPN) is obtained around the silica core. The
      properties of the composites, obtained using the hybrid nanoparticles, depend on
      the filler content and the amount of PMMA in the semi-IPN matrix. For composites
      with similar inorganic filler contents, the composites with low amounts of PMMA
      shell had higher modulus than those in which silica was used as the filler.

PMID- 25063107
TI  - The influence of low concentrations of a water soluble poragen on the material
      properties, antibiotic release, and biofilm inhibition of an acrylic bone cement.
AB  - Soluble particulate fillers can be incorporated into antibiotic-loaded acrylic
      bone cement in an effort to enhance antibiotic elution. Xylitol is a material
      that shows potential for use as a filler due to its high solubility and potential
      to inhibit biofilm formation. The objective of this work, therefore, was to
      investigate the usage of low concentrations of xylitol in a gentamicin-loaded
      cement. Five different cements were prepared with various xylitol loadings (0, 1,
      2.5, 5 or 10 g) per cement unit, and the resulting impact on the mechanical
      properties, cumulative antibiotic release, biofilm inhibition, and thermal
      characteristics were quantified. Xylitol significantly increased cement porosity
      and a sustained increase in gentamicin elution was observed in all samples
      containing xylitol with a maximum cumulative release of 41.3%. Xylitol had no
      significant inhibitory effect on biofilm formation. All measured mechanical
      properties tended to decrease with increasing xylitol concentration; however,
      these effects were not always significant. Polymerization characteristics were
      consistent among all groups with no significant differences found. The results
      from this study indicate that xylitol-modified bone cement may not be appropriate
      for implant fixation but could be used in instances where sustained, increased
      antibiotic elution is warranted, such as in cement spacers or beads.

PMID- 25063108
TI  - 5,10,15,20-tetrakis(4-carboxyl phenyl)porphyrin-CdS nanocomposites with intrinsic
      peroxidase-like activity for glucose colorimetric detection.
AB  - Here, we describe the design of a novel mimic peroxidase, nanocomposites composed
      by 5,10,15,20-tetrakis(4-carboxyl phenyl)-porphyrin (H2TCPP) and cadmium sulfide
      (CdS). The H2TCPP-CdS nanocomposites can catalyze oxidation of substrate 3,3,5,5
      tetramethylbenzidine (TMB) in the presence of H2O2 and form a blue product which
      can be seen by the naked eye in 5 min. The mechanism of the catalytic reaction
      originated from the generation of hydroxyl radical (.OH), which is a powerful
      oxidizing agent to oxidize TMB to produce a blue product. Then, we developed a
      colorimetric method that is highly sensitive and selective to detect glucose,
      combined with glucose oxidase (GOx). The proposed method allowed the detection of
      H2O2 concentration in the range of 4*10(-6)-1.4*10(-5)M and glucose in the range
      of 1.875*10(-5)-1*10(-4)M with detectable H2O2 concentration as low as 4.6*10(
      7)M and glucose as low as 7.02*10(-6)M, respectively. The results provided the
      theoretical basis of practical application in glucose detecting and peroxidase
      mimetic enzymes.

PMID- 25063109
TI  - Simulation and experimental results of optical and thermal modeling of gold
      nanoshells.
AB  - This paper proposes a generalized method for optical and thermal modeling of
      synthesized magneto-optical nanoshells (MNSs) for biomedical applications.
      Superparamagnetic magnetite nanoparticles with diameter of 9.5 +/- 1.4 nm are
      fabricated using co-precipitation method and subsequently covered by a thin layer
      of gold to obtain 15.8 +/- 3.5 nm MNSs. In this paper, simulations and detailed
      analysis are carried out for different nanoshell geometry to achieve a maximum
      heat power. Structural, magnetic and optical properties of MNSs are assessed
      using vibrating sample magnetometer (VSM), X-ray diffraction (XRD), UV-VIS
      spectrophotometer, dynamic light scattering (DLS), and transmission electron
      microscope (TEM). Magnetic saturation of synthesized magnetite nanoparticles are
      reduced from 46.94 to 11.98 emu/g after coating with gold. The performance of the
      proposed optical-thermal modeling technique is verified by simulation and
      experimental results.

PMID- 25063110
TI  - Experimental testing on free vibration behaviour for silicone rubbers proposed
      within lumbar disc prosthesis.
AB  - This research was focused on the damping capacity study of two types of silicone
      rubbers proposed as layers within total lumbar disc prostheses of ball-and-socket
      model. In order to investigate the damping capacity, the two silicone rubber
      types mainly differing by the molecular mass of polymeric matrix and the filler
      content, as was emphasized by scanning electron microscopy and differential
      scanning calorimetry, were subjected to free vibration testing. Using an adapted
      experimental installation, three kinds of damping testing were realised: tests
      without samples and tests with three samples of each type of silicone rubber (69
      ShA and 99 ShA). The free vibration tests were performed at a frequency of about
      6 Hz using a weight of 11.8 kg. The relative damping coefficient was determined
      by measuring of two successive amplitudes on the vibrogram and calculating of the
      logarithmic decrement. The test results with silicone rubber samples showed a
      relative damping coefficient of 0.058 and respectively 0.077, whilst test results
      without samples showed a relative damping coefficient of 0.042. These silicone
      rubbers were found to have acceptable damping properties to be used as layers
      placed inside the prosthetic components.

PMID- 25063111
TI  - Synthesis and characterization of nanocomposite scaffolds based on triblock
      copolymer of L-lactide, epsilon-caprolactone and nano-hydroxyapatite for bone
      tissue engineering.
AB  - The employment of biodegradable polymer scaffolds is one of the main approaches
      for achieving a tissue engineered construct to reproduce bone tissues, which
      provide a three dimensional template to regenerate desirable tissues for
      different applications. The main goal of this study is to design a novel triblock
      scaffold reinforced with nano-hydroxyapatite (nHA) for hard tissue engineering
      using gas foaming/salt leaching method with minimum solvent usage. With this end
      in view, the biodegradable triblock copolymers of l-lactide and epsilon
      caprolactone with different mol% were synthesized by ring-opening polymerization
      method in the presence of Sn(Oct)2 catalyst as initiator and ethylene glycol as
      co-initiator. The chemical compositions of biodegradable copolymers were
      characterized by means of FTIR and NMR. The thermal and crystallization behaviors
      of copolymers were characterized using TGA and DSC thermograms. Moreover, nano
      hydroxyapatite was synthesized by the chemical precipitation process and was
      thoroughly characterized by FTIR, XRD and TEM. Additionally, the nanocomposites
      with different contents of nHA were prepared by mixing triblock copolymer with
      nHA. Mechanical properties of the prepared nanocomposites were evaluated by
      stress-strain measurements. It was found that the nanocomposite with 30% of nHA
      showed the optimum result. Therefore, nanocomposite scaffolds with 30% nHA were
      fabricated by gas foaming/salt leaching method and SEM images were used to
      observe the microstructure and morphology of nanocomposites and nanocomposite
      scaffolds before and after cell culture. The in-vitro and cell culture tests were
      also carried out to further evaluate the biological properties. The results
      revealed that the porous scaffolds were biocompatible to the osteoblast cells
      because the cells spread and grew well. The resultant nanocomposites could be
      considered as good candidates for use in bone tissue engineering.

PMID- 25063112
TI  - Micro-scale abrasive wear behavior of medical implant material Ti-25Nb-3Mo-3Zr
      2Sn alloy on various friction pairs.
AB  - The micro-scale abrasion behaviors of surgical implant materials have often been
      reported in the literature. However, little work has been reported on the micro
      scale abrasive wear behavior of Ti-25Nb-3Mo-3Zr-2Sn (TLM) titanium alloy in
      simulated body fluids, especially with respect to friction pairs. Therefore, a
      TE66 Micro-Scale Abrasion Tester was used to study the micro-scale abrasive wear
      behavior of the TLM alloy. This study covers the friction coefficient and wear
      loss of the TLM alloy induced by various friction pairs. Different friction pairs
      comprised of ZrO2, Si3N4 and Al2O3 ceramic balls with 25.4mm diameters were
      employed. The micro-scale abrasive wear mechanisms and synergistic effect between
      corrosion and micro-abrasion of the TLM alloy were investigated under various
      wear-corrosion conditions employing an abrasive, comprised of SiC (3.5 +/- 0.5
      MUm), in two test solutions, Hanks' solution and distilled water. Before the
      test, the specimens were heat treated at 760 degrees C/1.0/AC+550 degrees
      C/6.0/AC. It was discovered that the friction coefficient values of the TLM alloy
      are larger than those in distilled water regardless of friction pairs used,
      because of the corrosive Hanks' solution. It was also found that the value of the
      friction coefficient was volatile at the beginning of wear testing, and it became
      more stable with further experiments. Because the ceramic balls have different
      properties, especially with respect to the Vickers hardness (Hv), the wear loss
      of the TLM alloy increased as the ball hardness increased. In addition, the wear
      loss of the TLM alloy in Hanks' solution was greater than that in distilled
      water, and this was due to the synergistic effect of micro-abrasion and
      corrosion, and this micro-abrasion played a leading role in the wear process. The
      micro-scale abrasive wear mechanism of the TLM alloy gradually changed from two
      body to mixed abrasion and then to three-body abrasion as the Vickers hardness of
      the balls increased.

PMID- 25063113
TI  - Development and characterization of hydrogels based on natural polysaccharides:
      policaju and chitosan.
AB  - The development of hydrogels based on natural polysaccharides was investigated by
      preparing mixtures of policaju/chitosan at weight ratios of 1:4 and 2:3.
      Utilizing dynamic light scattering (DLS) techniques for these mixtures, an
      increase on the hydrodynamic particle radius was observed varying their pH from
      3.0 to 12.0. Furthermore, a reduction of zeta-potential was also observed for the
      same pH interval. Following rounds of drying/hydration cycles at a specific pH
      value, hydrogel matrices were formed. The pore size distribution of these formed
      hydrogels was examined using scanning electron microscopy. Further FT-IR analyses
      confirmed a physical interaction between the polysaccharides policaju and
      chitosan. Swelling experiments revealed water uptake values, after 24h of
      immersion in water, close to 270% for 1:4, and 320% for 2:3 hydrogels. Finally,
      rheological measurements were then conducted in order to confirm hydrogel
      viscoelastic features. These results indicate a promising road to biomaterials
      fabrication and biomedical applications. 

PMID- 25063114
TI  - Electrochemically reduced graphene oxide-based electrochemical sensor for the
      sensitive determination of ferulic acid in A. sinensis and biological samples.
AB  - An electrochemically reduced graphene oxide (ERGO) modified glassy carbon
      electrode (GCE) was used as a new voltammetric sensor for the determination of
      ferulic acid (FA). The morphology and microstructure of the modified electrodes
      were characterized by scanning electron microscopy (SEM) and Raman spectroscopy
      analysis, and the electrochemical effective surface areas of the modified
      electrodes were also calculated by chronocoulometry method. Sensing properties of
      the electrochemical sensor were investigated by means of cyclic voltammetry (CV)
      and differential pulse voltammetry (DPV). It was found that ERGO was
      electrodeposited on the surface of GCE by using potentiostatic method. The
      proposed electrode exhibited electrocatalytic activity to the redox of FA because
      of excellent electrochemical properties of ERGO. The transfer electron number
      (n), electrode reaction rate constant (ks) and electron-transfer coefficient
      (alpha) were calculated as 1.12, 1.24s(-1), and 0.40, respectively. Under the
      optimized conditions, the oxidation peak current was proportional to FA
      concentration at 8.49 * 10(-8)mol L(-1) to 3.89 * 10(-5)mol L(-1) with detection
      limit of 2.06 * 10(-8)mol L(-1). This fabricated sensor also displayed acceptable
      reproducibility, long-term stability, and high selectivity with negligible
      interferences from common interfering species. The voltammetric sensor was
      successfully applied to detect FA in A. sinensis and biological samples with
      recovery values in the range of 99.91%-101.91%.

PMID- 25063115
TI  - Structural analysis of chitosan hydrogels containing polymeric nanocapsules.
AB  - The incorporation of different concentrations of polymeric nanocapsule
      suspensions into chitosan hydrogels is proposed, in order to study the structure
      of a formulation with the properties of great tissue adhesion and controlled
      release of the nanoencapsulated drugs, represented here by capsaicinoids. The
      gels presented acceptable acid pH values and the nanoparticles were visually
      observed in the system. A transition from the micrometer to the nanometer scales
      suggested that the nanocapsules are initially agglomerated in the hydrogel. A
      sedimentation tendency of the nanocapsules in the system was observed and only
      physical interaction between the chitosan chains and polymeric nanocapsules was
      verified. The hydrogels, despite the presence of nanocapsules, presented shear
      thinning properties and an elastic behavior under low and high frequencies,
      showing a very structured gel network. The observed variation in the elasticity
      of the hydrogels may arise from a decrease in the number of interactions and
      degree of entanglement between the chitosan chains, caused by the presence of
      nanoparticles. 

PMID- 25063116
TI  - Property peculiarities of the atelocollagen-hyaluronan conjugates crosslinked
      with a short chain di-oxirane compound.
AB  - Minimal amounts of a short-chain bifunctional crosslinker of about 1.3 nm length,
      the 1,4-butanediol-diglycidyl ether (BDDGE), were used to generate atelocollagen
      hyaluronan conjugates in hydrogel state. Two a priori constraints were considered
      in recipe/procedure developing: (i) working in nondenaturing conditions, and (ii)
      ensuring a low cytotoxicity of the final product. Both atelocollagen (aK) and
      hyaluronan (NaHyal) were accurately purified to reduce their molecular-weight
      dispersity, in order to ensure the reproducibility of hydrogels characteristics.
      1:5 aK:NaHyal weight ratios and 1:2.5 to 1:5 alpha-NH2:BDDGE molar ratios were
      found to be the most favorable recipe prescriptions that allow the obtaining of
      rheo-mechanically stable hydrogels, able to be manipulated during cell culturing
      protocols. Experiments revealed two unexpected effects due to the crosslinking
      reactions mediated by a short-chain molecule: (i) the occurrence of two
      thresholds in the rheological behavior of the hydrogels, related with the amount
      of added crosslinker, and (ii) a quasi-denaturation side-effect induced over the
      protein component by large or in excess amounts of crosslinker.

PMID- 25063117
TI  - Effect of laser treatment on the attachment and viability of mesenchymal stem
      cell responses on shape memory NiTi alloy.
AB  - The objectives of this study were to investigate the effect of laser-induced
      surface features on the morphology, attachment and viability of mesenchymal stem
      cells (MSCs) at different periods of time, and to evaluate the biocompatibility
      of different zones: laser-melted zone (MZ), heat-affected zone (HAZ) and base
      metal (BM) in laser-treated NiTi alloy. The surface morphology and composition
      were studied by scanning electron microscope (SEM) and X-ray photoemission
      spectroscopy (XPS), respectively. The cell morphology was examined by SEM while
      the cell counting and viability measurements were done by hemocytometer and 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric
      assay. The results indicated that the laser-induced surface features, such as
      surface roughening, presence of anisotropic dendritic pattern and complete
      surface Ni oxidation were beneficial to improve the biocompatibility of NiTi as
      evidenced by the highest cell attachment (4 days of culture) and viability (7
      days of culture) found in the MZ. The biocompatibility of the MZ was the best,
      followed by the BM with the HAZ being the worst. The defective and porous oxide
      layer as well as the coarse grained structure might attribute to the inferior
      cell attachment (4 days of culture) and viability (7 days of culture) on the HAZ
      compared with the BM which has similar surface morphology.

PMID- 25063118
TI  - PCL-coated hydroxyapatite scaffold derived from cuttlefish bone: in vitro cell
      culture studies.
AB  - In the present study, we examined the potential of using highly porous
      poly(epsilon-caprolactone) (PCL)-coated hydroxyapatite (HAp) scaffold derived
      from cuttlefish bone for bone tissue engineering applications. The cell culture
      studies were performed in vitro with preosteoblastic MC3T3-E1 cells in static
      culture conditions. Comparisons were made with uncoated HAp scaffold. The
      attachment and spreading of preosteoblasts on scaffolds were observed by
      Live/Dead staining Kit. The cells grown on the HAp/PCL composite scaffold
      exhibited greater spreading than cells grown on the HAp scaffold. DNA
      quantification and scanning electron microscopy (SEM) confirmed a good
      proliferation of cells on the scaffolds. DNA content on the HAp/PCL scaffold was
      significantly higher compared to porous HAp scaffolds. The amount of collagen
      synthesis was determined using a hydroxyproline assay. The osteoblastic
      differentiation of the cells was evaluated by determining alkaline phosphatase
      (ALP) activity and collagen type I secretion. Furthermore, cell spreading and
      cell proliferation within scaffolds were observed using a fluorescence
      microscope. 

PMID- 25063119
TI  - Effects of the nanotopographic surface structure of commercially pure titanium
      following anodization-hydrothermal treatment on gene expression and adhesion in
      gingival epithelial cells.
AB  - The long-term stability and maintenance of endosseous implants with anodized
      hydrothermally treated commercially pure titanium surfaces and a nanotopographic
      structure (SA-treated c.p.Ti) depend on the barrier function provided by the
      interface between the transmucosal portion of the implant surface and the peri
      implant epithelium. This study investigated the effects of extracellular and
      intracellular gene expression in adherent gingival epithelial cells cultured for
      1-7 days on SA-treated c.p.Ti implant surfaces compared to anodic oxide (AO)
      c.p.Ti and c.p.Ti disks. Scanning electron microscopy (SEM) showed filopodium
      like extensions bound closely to the nanotopographic structure of SA-treated
      c.p.Ti at day 7 of culture. Gene expressions of focal adhesion kinase, integrin
      alpha6beta4, and laminin-5 (alpha3, beta3, gamma2) were significantly higher on
      SA-treated c.p.Ti than on c.p.Ti or AO c.p.Ti after 7 days (P<0.05). Our results
      confirmed that gingival epithelial cells adhere to SA-treated c.p.Ti as the
      transmucosal portion of an implant, and that this interaction markedly improves
      expression of focal adhesion molecules and enhances the epithelial cell
      phenotype. The cellular gene expression responses driving extracellular and
      intracellular molecular interactions thus play an important role in maintenance
      at the interface between SA-treated c.p.Ti implant surfaces and the gingival
      epithelial cells.

PMID- 25063120
TI  - Plackett-Burman experimental design for bacterial cellulose-silica composites
      synthesis.
AB  - Bacterial cellulose-silica hybrid composites were prepared starting from wet
      bacterial cellulose (BC) membranes using Stober reaction. The structure and
      surface morphology of hybrid composites were examined by FTIR and SEM. The SEM
      pictures revealed that the silica particles are attached to BC fibrils and are
      well dispersed in the BC matrix. The influence of silica particles upon BC
      crystallinity was studied using XRD analysis. Thermogravimetric (TG) analysis
      showed that the composites are stable up to 300 degrees C. A Plackett-Burman
      design was applied in order to investigate the influence of process parameters
      upon silica particle sizes and silica content of BC-silica composites. The
      statistical model predicted that it is possible for silica particles size to vary
      the synthesis parameters in order to obtain silica particles deposed on BC
      membranes in the range from 34.5 to 500 nm, the significant parameters being
      ammonia concentration, reaction time and temperature. The silica content also
      varies depending on process parameters, the statistical model predicting that the
      most influential parameters are water-tetraethoxysilane (TEOS) ratio and reaction
      temperature. The antimicrobial behavior on Staphylococcus aureus of BC-silica
      composites functionalized with usnic acid (UA) was also studied, in order to
      create improved surfaces with antiadherence and anti-biofilm properties.

PMID- 25063121
TI  - Morphology and properties of poly vinyl alcohol (PVA) scaffolds: impact of
      process variables.
AB  - Successful engineering of functional biological substitutes requires scaffolds
      with three-dimensional interconnected porous structure, controllable rate of
      biodegradation, and ideal mechanical strength. In this study, we report the
      development and characterization of micro-porous PVA scaffolds fabricated by
      freeze drying method. The impact of molecular weight of PVA, surfactant
      concentration, foaming time, and stirring speed on pore characteristics,
      mechanical properties, swelling ratio, and rate of degradation of the scaffolds
      was characterized. Results show that a foaming time of 60s, a stirring speed of
      1,000 rpm, and a surfactant concentration of 5% yielded scaffolds with rigid
      structure but with interconnected pores. Study also demonstrated that increased
      foaming time increased porosity and swelling ratio and reduced the rigidity of
      the samples.

PMID- 25063122
TI  - Complex formation between ovalbumin and strong polyanion PSSNa: study of
      structure and properties.
AB  - The mixture system of long-chain polyelectrolyte complexed with a globular
      protein was investigated based on dynamic light scattering and turbidimetric
      measurements. We have discussed at different pH values the influence of high salt
      concentration and mass ratio (protein:PSSNa) on the behavior of the mixture. In
      dilute concentration regime, the PSSNa chain contracts at pHc by patch binding.
      We found two critical values of mass ratio: The first corresponds to the maximum
      shrinking of PSSNa. The second indicates the system that became more stable where
      the number of proteins attached to the PSSNa chain was constant. The screen of
      electrostatic interaction shows a high contribution of hydrophobic interaction at
      large salt concentration to form the coacervates. By building phase diagram, the
      continuity of pHphi1 in over whole range of salt concentrations and the widening
      of pH window (pHphi1-pHphi2) were observed. At certain salt concentrations, we
      can obtain the coexistence of two types of complex particles formed by
      electrostatic and hydrophobic interactions. 

PMID- 25063123
TI  - Microstructure and properties of alendronate-loaded calcium phosphate cement.
AB  - Calcium phosphate cement (CPC), as an injectable bone substitute material is
      significant in bone defect treatment. Drugs and biological molecules are often
      incorporated into CPC to promote the healing of bone defects and treat some bone
      diseases. In this work, alendronate (ALN)-loaded CPC was prepared and the
      influences of the content of ALN on the setting time, microstructure of hydrate
      porosity, mechanical strength, in vitro drug release, rheological properties and
      injectability of CPC were systematically investigated. The results showed that
      the addition of ALN had no effect on the final hydration product of CPC. The
      setting time of CPC was prolonged, while the prolonging effect became weak when
      the larger amount of ALN was added. With the increment of ALN content, the
      hydroxyapatite crystals of cured CPC became smaller, and the hydrated CPC became
      more compact with lower porosity, which resulted in the improvement of
      compressive strength of CPC with a drug-loaded amount less than 1wt%. The
      injectability was dramatically improved due to the addition of ALN, which was
      corresponding to the decrease of viscosity. The thixotropy of the CPC slurry was
      promoted with increasing the ALN content, which could enhance the stability of
      the slurry. However, it was worth noting that an inverted thixotropic loop
      appeared when the drug content was higher than 3.0wt%. During the in vitro drug
      release, the initial burst release turned up for all formulations and the degree
      of burst release was different from each other. This work would allow advances in
      understanding the effect of ALN on the setting process and physical and chemical
      properties of CPC, and we should think over the appropriate content when adding
      ALN into CPC.

PMID- 25063124
TI  - Mg- and/or Sr-doped tricalcium phosphate/bioactive glass composites: synthesis,
      microstructure and biological responsiveness.
AB  - Presently, there is an increasing interest towards the composites of calcium
      phosphates, especially beta-tricalcium phosphate (TCP), and bioactive glasses. In
      the present contribution, the recently developed BG_Ca/Mix glass has been used
      because its low tendency to crystallize allows to sinter the composites at
      relatively low temperature (i.e. 850 degrees C), thus minimizing the glass
      devitrification and the interaction with TCP. A further improvement is the
      introduction of lab-produced TCP powders doped with specific ions instead of non
      doped commercial powders, since the biological properties of materials for bone
      replacement can be modulated by doping them with certain metallic ions, such as
      Mg and Sr. Therefore, novel binary composites have been produced by sintering the
      BG_Ca/Mix glass with the addition of pure, Mg-substituted, Sr-substituted or
      Mg/Sr bisubstituted TCP powders. After an accurate characterization of the
      starting TCP powders and of the obtained samples, the composites have been used
      as three-dimensional supports for the culture of mouse calvaria-derived pre
      osteoblastic cells. The samples supported cell adhesion and proliferation and
      induced promising mechanisms of differentiation towards an osteoblastic
      phenotype. In particular, the Mg/Sr bi-doped samples seemed to better promote the
      differentiation process thus suggesting a combined stimulatory effect of Mg(2+)
      and Sr(2+) ions. 

PMID- 25063125
TI  - Magnetic Fe3 O 4 nanoparticles grafted with single-chain antibody (scFv) and
      docetaxel loaded beta-cyclodextrin potential for ovarian cancer dual-targeting
      therapy.
AB  - In order to improve the therapeutic efficiency and reduce the side effects on
      nonpathological cells and tissues, targeting drug delivery systems have gained
      more and more attraction. Here, we report a novel dual-targeting drug delivery
      system for ovarian cancer therapy. The inner core was made of iron oxide (Fe3O4)
      nanoparticles, synthesized by co-precipitation method. It was further surface
      functionalized with amine groups to link single-chain antibody (scFv) and beta
      cyclodextrin (beta-CD). Docetaxel (TXT) was finally included in the grafted beta
      CD. FTIR and XPS confirmed the reactions. SEM found that the diameters of these
      Fe3O4 nanoparticles before and after functionalization were around 40 nm.
      Magnetization test showed that these particles were superparamagnetic. The in
      vitro release of TXT was concentration-driven and sustained, depending on the
      renewal rate of release medium. The in vitro flow chamber experiment revealed its
      magnetic targeting property; modified ELISA and static binding experiments
      displayed its good affinity to Endoglin, indicating that our drug delivery system
      has the potential to be dual-targeted to ovarian cancer tissue by externally
      applied magnetic field and native active binding of grafted scFv to Endoglin,
      overexpressed by ovarian cancer tissue. MTT assays showed that the TXT released
      from this drug delivery system continuously inhibited the growth of Skov3 ovarian
      cancer cells in 72h, better than the control raw TXT. All these results
      demonstrated a promising dual-targeting drug delivery system with great potential
      for ovarian cancer therapy.

PMID- 25063126
TI  - Luminescent composite polymer fibers: in situ synthesis of silver nanoclusters in
      electrospun polymer fibers and application.
AB  - The purpose of this study is to prepare multifunctional polymer fibers. We report
      a simple and controllable method for in situ synthesis of Ag nanoclusters (NCs)
      in electrospun polymer fibers via a photochemical reaction. The prepared
      composite polymer fibers emit pink luminescence and the luminescence property can
      be optimized by pH and Ag(I) precursor concentration. The as-prepared Ag NCs in
      electrospun polymer fibers were mainly Ag2-5 with a quantum yield of 6.81% and a
      lifetime of 2.29 ns. The in situ growth of Ag NCs avoids excessive surface
      modifications which may cause the aggregation of Ag NCs in many ex situ assembly
      methods. The combination of Ag NCs with polymer fibers greatly improves the
      stability of Ag NCs and broadens their applications. The storage of Ag NCs
      becomes facilitative due to the formation of bulky mat. Furthermore, these
      luminescence composite polymer fibers show strong antibacterial activity against
      Staphylococcus aureus (S. aureus).

PMID- 25063127
TI  - Synthesis and characterization of gold nanotube/nanowire-polyurethane composite
      based on castor oil and polyethylene glycol.
AB  - Gold nanotubes/nanowires (GNT/NW) were synthesized by using the template-assisted
      electrodeposition technique and mixed with castor oil-polyethylene glycol based
      polyurethane (PU) to fabricate porous composite scaffolds for biomedical
      application. 100 and 50 ppm of GNT/NW were used to synthesize composites. The
      composite scaffolds were characterized by Fourier transform infrared
      spectroscopy, dynamic mechanical thermal analysis, differential scanning
      calorimetry, and scanning electron microscopy. Cell attachment on polyurethane
      GNT/NW composites was investigated using fat-derived mesenchymal stem cells.
      Addition of 50 or 100 ppm GNT/NW had significant effects on thermal, mechanical,
      and cell attachment of polyurethane. Higher crosslink density and better cell
      attachment and proliferation were observed in polyurethane containing 50 ppm
      GNT/NW. The results revealed that GNT/NW formed hydrogen bonding with the
      polyurethane matrix and improved the thermomechanical properties of
      nanocomposites. Compared with pure PU, better cellular attachment on polyurethane
      GNT/NW composites was observed resulting from the improved surface properties of
      composites.

PMID- 25063128
TI  - Evaluation of pristine and Eu 2O3-added MgB 2 ceramics for medical applications:
      hardness, corrosion resistance, cytotoxicity and antibacterial activity.
AB  - Nano- or micropowders of Eu2O3 were added to MgB2, resulting in a composition of
      (MgB2)0.975(EuO1.5)0.025. Pristine and doped samples were prepared using spark
      plasma sintering and tested for (i) Vickers hardness, (ii) pH evolution in
      phosphate-buffered saline solution, (iii) corrosion resistance (Tafel
      polarization curves), (iv) cytotoxicity (in vitro tests), and (v) antibacterial
      activity. Eu2O3 addition influenced the investigated properties. Solutions of
      MgB2-based samples show a relatively high saturation pH of 8.5. This value is
      lower than that of solutions incubated with Mg or other Mg-based biodegradable
      alloys reported in the literature. MgB2-based samples have lower electro
      corrosion rates than Mg. Their Vickers hardness is 6.8-10.2GPa, and these values
      are higher than those of biodegradable Mg-based alloys. MgB2 has low in vitro
      biocompatibility, good antibacterial activity against Escherichia coli, and mild
      activity against Staphylococcus aureus. Our results suggest that MgB2-based
      materials deserve attention in biomedical applications, such as implants or
      sterile medical instruments.

PMID- 25063129
TI  - Preparation and mechanical property of a novel 3D porous magnesium scaffold for
      bone tissue engineering.
AB  - Porous magnesium has been recently recognized as a biodegradable metal for bone
      substitute applications. A novel porous Mg scaffold with three-dimensional (3D)
      interconnected pores and with a porosity of 33-54% was produced by the fiber
      deposition hot pressing (FDHP) technology. The microstructure and morphologies of
      the porous Mg scaffold were characterized by scanning electron microscopy (SEM),
      and the effects of porosities on the microstructure and mechanical properties of
      the porous Mg were investigated. Experimental results indicate that the measured
      Young's modulus and compressive strength of the Mg scaffold are ranged in 0.10
      0.37 GPa, and 11.1-30.3 MPa, respectively, which are fairly comparable to those
      of cancellous bone. Such a porous Mg scaffold having a 3D interconnected network
      structure has the potential to be used in bone tissue engineering.

PMID- 25063130
TI  - Immobilization of phenylalanine-dehydrogenase on nano-sized polytaurine: a new
      platform for application of nano-polymeric materials on enzymatic biosensing
      technology.
AB  - A strategy of phenylalanine-dehydrogenase (PheDH) entrapment within the
      polytaurine matrix is demonstrated to probe the direct electrochemistry of
      phenylalanine (Pha). It was found that PheDH has been stably immobilized on
      glassy carbon electrode modified by polytaurine based on simple technique. Cyclic
      voltammetric study indicated that the oxidation process is irreversible and
      diffusion controlled. The number of exchanged electrons in the electro-oxidation
      process was obtained, and the data indicated that Pha is oxidized via one
      electron steps. The results revealed that Pha promotes the rate of oxidation by
      increasing the peak current. The diffusion coefficient and electron-transfer
      coefficient of Pha were found to be 0.2*10(-6)cm(2)s(-1) and 0.467, respectively.
      A sensitive, simple and time-saving differential-pulse voltammetric procedure was
      developed for the analysis of Pha. The results show that by using the proposed
      method, Pha can be determined with a detection limit of 9 nM.

PMID- 25063131
TI  - Bioresorption mechanisms of chitosan physical hydrogels: a scanning electron
      microscopy study.
AB  - Tissue-engineered biodegradable medical devices are widely studied and systems
      must present suitable balance between versatility and elaboration simplicity. In
      this work, we aim at illustrating that such equilibrium can be found by
      processing chitosan physical hydrogels without external cross-linker. Chitosan
      concentration, degree of acetylation, solvent composition, and neutralization
      route were modulated in order to obtain hydrogels exhibiting different physico
      chemical properties. The resulting in vivo biological response was investigated
      by scanning electron microscopy. "Soft" hydrogels were obtained from chitosan of
      high degree of acetylation (35%) and by the neutralization with gaseous ammonia
      of a chitosan acetate aqueous solutions presenting low polymer concentration
      (Cp=1.6% w/w). "Harder" hydrogels were obtained from chitosan with lower degree
      of acetylation (5%) and after neutralization in sodium hydroxide bath (1M) of
      hydro-alcoholic chitosan solutions (50/50 w/w water/1,2-propanediol) with a
      polymer concentration of 2.5% w/w. Soft and hard hydrogels exhibited
      bioresorption times from below 10 days to higher than 60 days, respectively. We
      also evidenced that cell colonization and neo-vascularization mechanisms depend
      on the hydrogel-aggregated structure that is controlled by elaboration conditions
      and possibly in relation with mechanical properties. Specific processing
      conditions induced micron-range capillary formation, which can be assimilated to
      colonization channels, also acting on the resorption scenario.

PMID- 25063132
TI  - MRI-compatible Nb-60Ta-2Zr alloy used for vascular stents: haemocompatibility and
      its correlation with protein adsorption.
AB  - Nb-60Ta-2Zr is a newly developed MRI-compatible alloy used for vascular stents.
      In this work, its haemocompatibility was investigated, including platelet
      adhesion (lactate dehydrogenase activity), platelet activation (P-selectin
      expression), coagulation and haemolysis. For comparison, parallel assessments for
      these factors were performed for the niobium, tantalum, 316L stainless steel
      (316L SS) and L605 Co-Cr alloy (L605). In addition, albumin and fibrinogen were
      selected to examine the correlation of protein adsorption with platelet adhesion
      and metal surface properties. The propensity for platelet adhesion and activation
      on the Nb-60Ta-2Zr alloy was at nearly the same level as that for Nb and Ta but
      was slightly less than those of 316L SS and L605. The mitigated platelet adhesion
      and activation of the Nb-60Ta-2Zr alloy is associated with its decreased
      adsorption of fibrinogen. The Nb-60Ta-2Zr alloy has a longer clotting time and
      exhibits significantly superior thromboresistance than 316L SS and L605.
      Moreover, the haemolysis rate of the Nb-60Ta-2Zr alloy satisfies the bio-safety
      requirement of the ISO 10993-4 standard. The favourable haemocompatiblity of the
      Nb-60Ta-2Zr alloy provides evidence of its good biocompatibility and of its
      suitability as a candidate stent material. 

PMID- 25063133
TI  - Gelatin functionalised porous titanium alloy implants for orthopaedic
      applications.
AB  - In the present work, we studied the immobilisation of the biopolymer gelatin onto
      the surface of three dimensional (3D) regular Ti6Al4V porous implants to improve
      their surface bio-activity. The successful immobilisation of the gelatin coating
      was made possible by a polydopamine interlayer, a polymer coating inspired by the
      adhesive nature of mussels. The presence of both coatings was first optimised on
      two dimensional titanium (2D Ti) substrates and confirmed by different techniques
      including X-ray photelectron spectroscopy, contact angle measurements, atomic
      force microscopy and fluorescence microscopy. Results showed homogeneous coatings
      that are stable for at least 24h in phosphate buffer at 37 degrees C. In a next
      step, the coating procedure was successfully transferred to 3D Ti6Al4V porous
      implants, which indicates the versatility of the applied coating procedure with
      regard to complex surface morphologies. Furthermore, the bio-activity of these
      stable gelatin coatings was enhanced by applying a third and final coating using
      the cell-attractive protein fibronectin. The reproducible immobilisation process
      allowed for a controlled biomolecule presentation to the surrounding tissue. This
      newly developed coating procedure outperformed the previously reported
      silanisation procedure for immobilising gelatin. In vitro cell adhesion and
      culture studies with human periosteum-derived cells showed that the investigated
      coatings did not compromise the biocompatible nature of Ti6Al4V porous implants,
      but no distinct biological differences between the coatings were found. 

PMID- 25063134
TI  - Enhancement of valve metal osteoconductivity by one-step hydrothermal treatment.
AB  - In this study, we produced super-hydrophilic surfaces of valve metals (Ti, Nb, Ta
      and Zr) by one-step hydrothermal treatment. Their surface characteristics and
      osteoconductivity using an in vivo test were then assessed. These data were
      compared with that of as-polished, as-anodized and both anodized+hydrothermally
      treated samples. Changes in surface chemistry, surface morphology and structure
      were investigated by X-ray photoelectron spectroscopy, scanning electron
      microscopy, and X-ray diffractometry. The results revealed that the water contact
      angles of valve metals were decreased by hydrothermal treatment and continued to
      reduce dramatically until lower than 10 degrees  after being immersed in
      phosphate buffered solution. By producing super-hydrophilic surfaces, the
      osteoconductivity of these hydrothermally treated valve metals was enhanced by up
      to 55%.

PMID- 25063135
TI  - Inorganically modified diatomite as a potential prolonged-release drug carrier.
AB  - Inorganic modification of diatomite was performed with the precipitation product
      of partially neutralized aluminum sulfate solution at three different mass
      ratios. The starting and the modified diatomites were characterized by SEM-EDS,
      FTIR, thermal analysis and zeta potential measurements and evaluated for drug
      loading capacity in adsorption batch experiments using diclofenac sodium (DS) as
      a model drug. In vitro drug release studies were performed in phosphate buffer
      pH6.8 from comprimates containing: the drug adsorbed onto the selected modified
      diatomite sample (DAMD), physical mixture of the drug with the selected modified
      diatomite sample (PMDMD) and physical mixture of the drug with the starting
      diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite
      samples was performed on mice. High adsorbent loading of the selected modified
      diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates
      containing adsorbed DS in the amount near to its therapeutic dose. Drug release
      studies demonstrated prolonged release of DS over a period of 8h from both DAMD
      comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release
      kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and
      Bhaskar models, indicating that the release mechanism was a combination of non
      Fickian diffusion and ion exchange process. 

PMID- 25063136
TI  - Response to the letter to the editor: measurement of the uniaxial mechanical
      properties of healthy and atherosclerotic human coronary arteries.

PMID- 25063137
TI  - Hemocompatibility testing according to ISO 10993-4: discrimination between
      pyrogen- and device-induced hemostatic activation.
AB  - Next to good hemocompatibility performance of new medical devices, which has to
      be tested according to the ISO 10993-4, the detection of pyrogen-contaminated
      devices plays a pivotal role for safe device application. During blood contact
      with pyrogen-contaminated devices, intense inflammatory and hemostatic reactions
      are feared. The aim of our study was to investigate the influence of pyrogenic
      contaminations on stents according to the ISO 10993-4. The pyrogens of different
      origins like lipopolysaccharides (LPS), purified lipoteichoic acid (LTA) or
      zymosan were used. These pyrogens were dried on stents or dissolved and
      circulated in a Chandler-loop model for 90 min at 37 degrees C with human blood.
      Before and after circulation, parameters of the hemostatic system including
      coagulation, platelets, complement and leukocyte activation were investigated.
      The complement system was activated by LPS isolated from Klebsiella pneumoniae
      and Pseudomonas aeruginosa and by LTA. Leukocyte activation was triggered by LPS
      isolated from K. pneumoniae, LTA and zymosan, whereas coagulation and platelet
      activation were only slightly influenced. Our data indicate that pyrogen
      contaminated devices lead to an alteration in the hemostatic response when
      compared to depyrogenized devices. Therefore, pyrogenicity testing should be
      performed prior to hemocompatibility tests according to ISO 10993-4 in order to
      exclude hemostatic activation induced by pyrogen contaminations.

PMID- 25063138
TI  - TiO2 beads and TiO2-chitosan beads for urease immobilization.
AB  - The aim of the present study is to synthesize TiO2 beads for urease
      immobilization. Two different strategies were used to immobilize the urease on
      TiO2 beads. In the first method (A), urease enzyme was immobilized onto TiO2
      beads by adsorption and then crosslinking. In the second method (B), TiO2 beads
      were coated with chitosan-urease mixture. To determine optimum conditions of
      immobilization, different parameters were investigated. The parameters of
      optimization were initial enzyme concentration (0.5; 1; 1.5; 2mg/ml), alginate
      concentration (1; 2; 3%), glutaraldehyde concentration (1; 2; 3% v/v) and
      chitosan concentration (2; 3; 4 mg/ml). The optimum enzyme concentrations were
      determined as 1.5mg/ml for A and 1.0mg/ml for B. The other optimum conditions
      were found 2.0% (w/v) for alginate concentration (both A and B); 3.0mg/ml for
      chitosan concentration (B) and 2.0% (v/v) for glutaraldehyde concentration (A).
      The optimum temperature (20-60 degrees C), optimum pH (3.0-10.0), kinetic
      parameters, thermal stability (4-70 degrees C), pH stability (4.0-9.0),
      operational stability (0-230 min) and reusability (20 times) were investigated
      for characterization. The optimum temperatures were 30 degrees C (A), 40 degrees
      C (B) and 35 degrees C (soluble). The temperature profiles of the immobilized
      ureases were spread over a large area. The optimum pH values for the soluble
      urease and immobilized urease prepared by using methods (A) and (B) were found to
      be 7.5, 7.0, 7.0, respectively. The thermal stabilities of immobilized enzyme
      sets were studied and they maintained 50% activity at 65 degrees C. However, at
      this temperature free urease protected only 15% activity.

PMID- 25063139
TI  - Development of a highly sensitive MIP based-QCM nanosensor for selective
      determination of cholic acid level in body fluids.
AB  - Determination of cholic acid is very important and necessary in body fluids due
      to its both pharmaceutical and clinical significance. In this study, a quartz
      crystal microbalance (QCM) nanosensor, which is imprinted cholic acid, has been
      developed for the assignation of cholic acid. The cholic acid selective memories
      have been generated on QCM electrode surface by using molecularly imprinted
      polymer (MIP) based on methacryloylamidohistidine-copper (II) (MAH-Cu(II)) pre
      organized monomer. The cholic acid imprinted nanosensor was characterized by
      atomic force microscopy (AFM) and then analytical performance of the cholic acid
      imprinted QCM nanosensor was studied. The detection limit was found to be
      0.0065MUM with linear range of 0.01-1,000 MUM. Moreover, the high value of
      Langmuir constant (b) (7.3*10(5)) obtained by Langmuir graph showed that the
      cholic acid imprinted nanosensor had quite strong binding sites affinity. At the
      last step of this procedure, cholic acid levels in body fluids were determined by
      the prepared imprinted QCM nanosensor.

PMID- 25063140
TI  - Surface modification of polypropylene membrane by polyethylene glycol graft
      polymerization.
AB  - Polypropylene hollow fiber microporous membranes have been used in a wide range
      of applications, including blood oxygenator. The hydrophobic feature of the
      polypropylene surface causes membrane fouling. To minimize fouling, a
      modification consisting of three steps: surface activation in H2 and O2 plasma,
      membrane immersion in polyethylene glycol (PEG) and plasma graft polymerization
      was performed. The membranes were characterized by contact angle measurement,
      Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy
      (XPS), tensile test, scanning electron microscopy (SEM) and atomic force
      microscopy (AFM). Oxygen transfer of modified membranes was also tested. The
      stability of grafted PEG was measured in water and in phosphate buffer saline
      (PBS) at 37 degrees C. Blood compatibility of modified surfaces was evaluated by
      the platelet adhesion method. Water contact angel reduction from 110 degrees  to
      72 degrees  demonstrates the enhanced hydrophilicity, and XPS results verify the
      presence of oxygenated functional groups due to the peak existence in 286 eV as a
      result of PEG grafting. The results clearly indicate that plasma graft
      polymerization of PEG is an effective way for antifouling improvement of
      polypropylene membranes. Also, the results show that oxygen transfer changes in
      PEG grafted membranes are not significant.

PMID- 25063141
TI  - A study of the mechanical properties and cytocompatibility of lactide and
      caprolactone based scaffolds filled with inorganic bioactive particles.
AB  - The mechanical properties of highly porous (90% porosity) poly(l-lactide) (PLLA),
      poly(epsilon-caprolactone) (PCL) and poly(l-lactide/epsilon-caprolactone) (PLCL)
      were investigated. Young's modulus of non-porous PLLA, PCL and PLCL dropped from
      2263.4, 183.7 and 5.7 MPa to 16.8, 1.0 and 1.0 MPa, respectively, for their ~90%
      porous counterparts. Elongation at break of PCL decreased noticeably with
      porosity fraction while PLCL maintained a highly elastomeric character and strain
      recovery capacity even in the presence of pores. Inorganic bioactive particles
      (hydroxyapatite or bioglass) were added to confer bioactivity to the
      aforementioned synthetic bioresorbable polymers, and their effect on the
      mechanical properties was also investigated. Addition of 15 vol.% of inorganic
      bioactive particles increased the Young's modulus of highly porous PLLA from 16.2
      to ~30 MPa. On the contrary, the difference between Young's modulus of filled and
      unfilled PCL and PLCL scaffolds was not statistically significant. Finally, an in
      vitro study of the cytocompatibility and adhesion of adipose derived stem cells
      (ADSCs) was conducted. The observed viability and excellent adhesion of these
      cells to both porous and non-porous templates indicate that the employed
      materials can be good candidates for application in tissue engineering.

PMID- 25063142
TI  - Delta-sleep inducing peptide entrapment in the charged macroporous matrices.
AB  - Various biomolecules, for example proteins, peptides etc., entrapped in polymer
      matrices, impact interactions between matrix and cells, including stimulation of
      cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses
      numerous beneficial properties, including its abilities in burn treatment and
      neuronal protection. DSIP entrapment in two macroporous polymer matrices based on
      copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co
      DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA
      MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively
      charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively
      charged Co-AA-MBAA was only 2-6%. DSIP release from Co-DMAEMA-MBAA was observed
      in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water
      or 25% ethanol, thus ionic strength was a reason of this process.

PMID- 25063143
TI  - Antibacterial efficiency of vermiculite/chlorhexidine nanocomposites and results
      of the in vivo test of harmlessness of vermiculite.
AB  - Clay minerals have been proposed as very useful materials for modulating drug
      delivery. These are the commonly used materials in pharmaceutical production both
      as inorganic carriers or active agents. We focused on the development of suitable
      long-acting material for local treatment of oral infection where clay minerals
      act as inorganic drug carriers. Organovermiculites with antibacterial activity
      were prepared by ion exchange reactions using different concentrations of
      chlorhexidine diacetate. The samples were characterized by X-ray diffraction
      (XRD), Fourier transform infrared spectroscopy (FTIR) and thermal analysis (TGA).
      The antibacterial activity was evaluated by finding the minimum inhibitory
      concentration (MIC). All studied organoclays possessed good antibacterial
      activity after 24h exposure against Escherichia coli, Enterococcus faecalis and
      particularly against Staphylococcus aureus. Pseudomonas aeruginosa however proved
      very resistant as only the sample with the highest concentration of CA that
      successfully inhibited bacterial growth. Furthermore, clay mineral vermiculite
      was subjected to in vivo toxicological analysis and its influence on
      gastrointestinal tract during its oral application was investigated. Tissue
      samples from buccal mucosa, tongue, esophagus, stomach, terminal duodenum, small
      intestine, caecum, distal colon and liver were subjected to histological
      examination, both macroscopically and microscopically. Neither systemic nor local
      reactions were observed. Therefore the toxicity of vermiculite to a mammal model
      organism can be excluded. 

PMID- 25063144
TI  - Three dimensional chitosan scaffolds influence the extra cellular matrix
      expression in Schwann cells.
AB  - Chitosan is a choice material for scaffolds in regenerative medicine. One of the
      applications is to bridge the damaged peripheral nerves. Previous studies showed
      that combination of chitosan conduits and cultured Schwann cells could increase
      the opportunity for re-connection of broken nerves. It has also been known that
      Schwann cells can produce the ECM components which are critical for nerve
      regeneration. In this study, we used the rat Schwann cells (RSCs) grown on porous
      chitosan scaffolds for quantitative analysis of ECM protein expression. The RSCs
      grown on chitosan scaffolds secreted higher amount of laminin and collagen 4 than
      those grown on the plane. The increased laminin and collagen 4 produced by
      Schwann cells could create a preferable condition for stimulating peripheral
      nerve regeneration. 

PMID- 25063145
TI  - Effects of material, coating, design and plaque composition on stent deployment
      inside a stenotic artery--finite element simulation.
AB  - Finite-element simulations have been carried out to study the effects of material
      choice, drug eluting coating and cell design on the mechanical behaviour of
      stents during deployment inside a stenotic artery. Metallic stents made of
      materials with lower yield stress and weaker strain hardening tend to experience
      higher deformation and stronger dogboning and recoiling, but less residual
      stresses. Drug eluting coatings have limited effect on stent expansion,
      recoiling, dogboning and residual stresses. Stent expansion is mainly controlled
      by the radial stiffness of the stent which is closely associated with the stent
      design. In particular, open-cell design tends to have easier expansion and higher
      recoiling than closed-cell design. Dogboning is stronger for slotted tube design
      and open-cell sinusoidal design, but reduced significantly for designs
      strengthened with longitudinal connective struts. After deployment, the maximum
      von Mises stress appears to locate at the U-bends of stent cell struts, with
      varying magnitude that depends on the materials and severity of plastic
      deformation. For the artery-plaque system, the stresses, especially in the plaque
      which is in direct contact with the stent, appear to be distinctly different for
      different stent designs and materials in terms of both distribution and
      magnitude. The plaque composition also strongly affects the expansion behaviour
      of the stent-artery system and modifies the stresses on the plaque. 

PMID- 25063146
TI  - Optimization of poly(L-lactic acid)/segmented polyurethane electrospinning
      process for the production of bilayered small-diameter nanofibrous tubular
      structures.
AB  - The present study is focused on the electrospinning process as a versatile
      technique to obtain nanofibrous tubular structures for potential applications in
      vascular tissue engineering. A bilayered scaffolding structure composed of poly(L
      lactic acid) (PLLA)/bioresorbable segmented polyurethane (SPEU) blends for small
      diameter (5mm) vascular bypass grafts was obtained by multilayering
      electrospinning. Polymer blend ratios were chosen to mimic the media and
      adventitia layers. The influence of the different electrospinning parameters into
      the fiber formation, fiber morphology and fiber mean diameter for PLLA, SPEU and
      two PLLA/SPEU blends were studied. Flat and two-parallel plate collectors were
      used to analyze the effect of the electrostatic field on the PLLA nanofiber
      alignment in the rotating mandrel. Membrane topography resulted in random or
      aligned nanofibrous structures depending on the auxiliary collector setup used.
      Finally, composition, surface hydrophilicity, thermal properties and morphology
      of nanofibrous scaffolds were characterized and discussed. Since the development
      of tissue engineered microvascular prostheses is still a challenge, the prepared
      scaffolding tubular structures are promising candidates for vascular tissue
      engineering. 

PMID- 25063147
TI  - Determination of buprenorphine by differential pulse voltammetry on carbon paste
      electrode using SDS as an enhancement factor.
AB  - In the present study, a facile electrochemical approach is proposed for the
      determination of buprenorphine (BPR) in the presence of sodium dodecyl sulfate
      (SDS). SDS was applied for amplification of oxidation signal. Carbon paste
      electrode (CPE) used as working electrode and cyclic voltammetry (CV),
      differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy
      (EIS) were carried out in phosphate buffer solution (pH3.0). Under optimal
      experimental conditions, the oxidation current increased with the addition of BPR
      in the sample and two dynamic ranges obtained from 4.00 nM to 0.126 MUM and from
      0.126 to 0.317 MUM by DPV and exhibited a low detection limit (LOD) of 1.33 nM
      (S/N=3). This offered method has been used for the determination of BPR in the
      real samples and has validated with the recovery test for BPR spiked urine
      samples. The result demonstrated that this method is a simple, sensitive, rapid,
      low-cost, and stable method for BPR detection.

PMID- 25063148
TI  - IGF-1 release kinetics from chitosan microparticles fabricated using
      environmentally benign conditions.
AB  - The main objective of this study is to maximize growth factor encapsulation
      efficiency into microparticles. The novelty of this study is to maximize the
      encapsulated growth factors into microparticles by minimizing the use of organic
      solvents and using relatively low temperatures. The microparticles were
      fabricated using chitosan biopolymer as a base polymer and cross-linked with
      tripolyphosphate (TPP). Insulin like-growth factor-1 (IGF-1) was encapsulated
      into microparticles to study release kinetics and bioactivity. In order to
      authenticate the harms of using organic solvents like hexane and acetone during
      microparticle preparation, IGF-1 encapsulated microparticles prepared by the
      emulsification and coacervation methods were compared. The microparticles
      fabricated by emulsification method have shown a significant decrease (p<0.05) in
      IGF-1 encapsulation efficiency, and cumulative release during the two-week
      period. The biocompatibility of chitosan microparticles and the bioactivity of
      the released IGF-1 were determined in vitro by live/dead viability assay. The
      mineralization data observed with von Kossa assay, was supported by mRNA
      expression levels of osterix and runx2, which are transcription factors necessary
      for osteoblasts differentiation. Real time RT-PCR data showed an increased
      expression of runx2 and a decreased expression of osterix over time, indicating
      differentiating osteoblasts. Chitosan microparticles prepared in optimum
      environmental conditions are a promising controlled delivery system for cells to
      attach, proliferate, differentiate and mineralize, thereby acting as a suitable
      bone repairing material. 

PMID- 25063149
TI  - Anhydric maleic functionalization and polyethylene glycol grafting of lactide-co
      trimethylene carbonate copolymers.
AB  - Lactide and trimethylene carbonate copolymers were successfully grafted with
      polyethylene glycol via previous functionalization with maleic anhydride and
      using N,N'-diisopropylcarbodiimide as condensing agent. Maleinization led to
      moderate polymer degradation. Specifically, the weight average molecular weight
      decreased from 36,200 to 30,200 g/mol for the copolymer having 20 mol% of
      trimethylene carbonate units. Copolymers were characterized by differential
      scanning calorimetry, thermogravimetry and X-ray diffraction. Morphology of
      spherulites and lamellar crystals was evaluated with optical and atomic force
      microscopies, respectively. The studied copolymers were able to crystallize
      despite the randomness caused by the trimethylene carbonate units and the lateral
      groups. Contact angle measurements indicated that PEG grafted copolymers were
      more hydrophilic than parent copolymers. This feature justified that enzymatic
      degradation in lipase medium and proliferation of both epithelial-like and
      fibroblast-like cells were enhanced. Grafted copolymers were appropriate to
      prepare regular drug loaded microspheres by the oil-in-water emulsion method.
      Triclosan release from loaded microspheres was evaluated in two media.

PMID- 25063150
TI  - Influence of electropolishing and anodic oxidation on morphology, chemical
      composition and corrosion resistance of niobium.
AB  - The work presents results of the studies performed on electropolishing of pure
      niobium in a bath that contained: sulphuric acid, hydrofluoric acid, ethylene
      glycol and acetanilide. After the electropolishing, the specimens were subjected
      to anodic passivation in a 1moldm(-3) phosphoric acid solution at various
      voltages. The surface morphology, thickness, roughness and chemical composition
      of the resulting oxide layers were analysed. Thusly prepared niobium samples were
      additionally investigated in terms of their corrosion resistance in Ringer's
      solution. The electropolished niobium surface was determined to be smooth and
      lustrous. The anodisation led to the growth of barrier-like oxide layers, which
      were enriched in phosphorus species. 

PMID- 25063151
TI  - Effect of glucose content on thermally cross-linked fibrous gelatin scaffolds for
      tissue engineering.
AB  - Thermally cross-linked glucose-containing electrospun gelatin meshes were studied
      as possible cell substrate materials. FTIR analysis was used to study the effect
      of glucose on cross-linking reactions. It was found that the presence of glucose
      increases the extent of cross-linking of fibrous gelatin scaffolds, which in
      return determines scaffold properties and their usability in tissue engineering
      applications. Easy to handle fabric-like scaffolds were obtained from blends
      containing up to 15% glucose. Maximum extent of cross-linking was reached at
      nearly 20% glucose content. Cross-linking effectively resulted in decreased
      solubility and increased resistance to enzymatic degradation. Preliminary short
      term cell culture experiments indicate that such thermally cross-linked gelatin
      glucose scaffolds are suitable for tissue engineering applications. 

PMID- 25063152
TI  - Novel humic acid-bonded magnetite nanoparticles for protein immobilization.
AB  - The present paper is the first report that introduces (i) a useful methodology
      for chemical immobilization of humic acid (HA) to aminopropyltriethoxysilane
      functionalized magnetite iron oxide nanoparticles (APS-MNPs) and (ii) human serum
      albumin (HSA) binding to the obtained material (HA-APS-MNPs). The newly prepared
      magnetite nanoparticle was characterized by using Fourier transform infrared
      spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), thermogravimetric analysis (TGA), and elemental analysis.
      Results indicated that surface modification of the bare magnetite nanoparticles
      (MNPs) with aminopropyltriethoxysilane (APS) and HA was successfully performed.
      The protein binding studies that were evaluated in batch mode exhibited that HA
      APS-MNPs could be efficiently used as a substrate for the binding of HSA from
      aqueous solutions. Usually, recovery values higher than 90% were found to be
      feasible by HA-APS-MNPs, while that value was around 2% and 70% in the cases of
      MNPs and APS-MNPs, respectively. Hence, the capacity of MNPs was found to be
      significantly improved by immobilization of HA. Furthermore, thermal degradation
      of HA-APS-MNPs and HSA bonded HA-APS-MNPs was evaluated in terms of the Horowitz
      Metzger equation in order to determine kinetic parameters for thermal
      decomposition. Activation energies calculated for HA-APS-MNPs (20.74 kJmol(-1))
      and HSA bonded HA-APS-MNPs (33.42 kJmol(-1)) implied chemical immobilization of
      HA to APS-MNPs, and tight interactions between HA and HA-APS-MNPs.

PMID- 25063153
TI  - Chitosan-silica hybrid porous membranes.
AB  - Chitosan-silica porous hybrids were prepared by a novel strategy in order to
      improve the mechanical properties of chitosan (CHT) in the hydrogel state. The
      inorganic silica phase was introduced by sol-gel reactions in acidic medium
      inside the pores of already prepared porous scaffolds. In order to make the
      scaffolds insoluble in acidic media chitosan was cross-linked by genipin (GEN)
      with an optimum GEN concentration of 3.2 wt.%. Sol-gel reactions took place with
      Tetraethylorthosilicate (TEOS) and 3-glycidoxypropyltrimethoxysilane (GPTMS)
      acting as silica precursors. GPTMS served also as a coupling agent between the
      free amino groups of chitosan and the silica network. The morphology study of the
      composite revealed that the silica phase appears as a layer covering the chitosan
      membrane pore walls. The mechanical properties of the hybrids were characterized
      by means of compressive stress-strain measurements. By immersion in water the
      hybrids exhibit an increase in elastic modulus up to two orders of magnitude.

PMID- 25063154
TI  - Fabrication of dispersible calcium phosphate nanocrystals via a modified Pechini
      method under non-stoichiometric conditions.
AB  - Various techniques for preparing ceramic nanoparticles have been developed;
      however, most of them start from a preparation of precursor nanoparticles that
      are generally amorphous or in poorly crystallized phases. Thermal treatments used
      to obtain crystalline phases typically result in the sintering of the products
      into large polycrystals. In this study, we developed a process to fabricate
      dispersible hydroxyapatite (HAp; Ca10(PO4)6(OH)2) nanocrystals via a modified
      Pechini method, which is a sol-gel like solid-state synthesis method for the
      preparation of multicomponent oxides. We demonstrated that the HAp nanocrystals
      sintered into large polycrystals ranging in size from several tens to several
      hundreds of microns via a conventional Pechini method using the stoichiometric
      Ca/P molar ratio of 1.67. When the Ca/P molar ratio in the precursor was >1.67, a
      mixture of HAp nanocrystals and removable CaO matrix was obtained. The HAp
      nanocrystals were dispersed in aqueous media mostly in the form of nanoparticles
      when the amount of CaO matrix was sufficiently greater than the amount of HAp. 

PMID- 25063155
TI  - Hydrophobically modified chitosan: a bio-based material for antimicrobial active
      film.
AB  - The objective of the present research was to improve the hydrophobicity of
      chitosan, while retaining its antibacterial activity, through the grafting of
      dodecenyl succinyl chains onto phthaloyl chitosan, mainly at the C-6 position.
      Dodecenyl succinylated phthaloyl chitosan (DS-g-PHCTS) was synthesized via
      phthaloylation-dodecenyl succinylation-hydrazinolysis. The obtained derivatives
      were characterized by FTIR, (1)H NMR and XRD. Hydrazinolysis time was found to be
      a key factor in controlling the substitution of dodecenyl succinyl chains and
      phthalimido groups of the final product. DS-g-PHCTS - with a grafting degree of
      dodecenyl succinyl chains and a substitution degree of phthalimido groups of 0.73
      and 0.39, respectively - exhibited an anhydrous crystal structure and the same
      solubility behavior as native chitosan. The introduction of hydrophobic alkyl
      chains provided DS-g-PHCTS with enhanced antibacterial activity against Gram
      positive bacteria. In addition, DS-g-PHCTS film showed more effective bacterial
      growth inhibition and better water vapor barrier property under neutral pH
      condition than chitosan film. The results suggested that DS-g-PHCTS film could be
      potentially used as antibacterial active film.

PMID- 25063156
TI  - Hydrothermal synthesis and thermal evolution of carbonate-fluorhydroxyapatite
      scaffold from cuttlefish bones.
AB  - Phase composition, crystal structure and morphology of carbonated
      fluor/hydroxyapatite synthesized hydrothermally from aragonitic cuttlefish bones
      were studied by powder X-ray diffraction (PXRD), Fourier transform infrared
      spectroscopy (FTIR), and scanning electron microscopy (SEM) combined with energy
      dispersive X-ray spectroscopy (EDS). The product of synthesis has been
      characterized as carbonated fluor/hydroxyapatite with carbonate incorporated
      inside channel (A-type) and substituted for the PO4(3-) group (B-type). The
      vibration band at 874 cm(-1) assigned to bending (nu2) mode undoubtedly confirmed
      carbonate substituted for PO4(3-) group, while the band at 880 cm(-1) was
      attributed to A-type carbonate substitution. The additional sharp and intense
      band at 865 cm(-1) considered as "non-apatitic" carbonate substitution is not
      assigned with certainty so far. Evolution of CO2 from tetrahedral (PO4(3-)) sites
      with the increase in heat-treatment temperature is evident by the changes in
      tetrahedral bond lengths and angles, as obtained by the Rietveld structure
      refinement. Also, changes in the isotropic temperature parameters for the 2a site
      point to A-type carbonate incorporation as well.

PMID- 25063157
TI  - Nanoindentation analysis of alphatricalcium phosphate-poly(lactide-co-glycolide)
      nanocomposite degradation.
AB  - The internal mechanical property characteristics as functions of position and
      degradation time of PLGA(50:50)-alphaTCP nanocomposites of varying ceramic
      polymer ratios degraded in an aqueous medium have been assessed using depth
      sensing nanoindentation. The addition of nanoparticulate alphaTCP increases the
      elastic modulus of undegraded specimens from 3.72 +/- 0.12 GPa for pure
      PLGA(50:50) samples to 7.23 +/- 0.16 GPa recorded for undegraded 40 wt.% TCP
      nanocomposites. Additionally alphaTCP incorporation decreases the viscoelastic
      loss tangent from 0.189 +/- 0.040 measured for pure undegraded PLGA(50:50) to an
      average of 0.091 +/- 0.006 for undegraded ceramic-polymer composites. No
      variation in viscosity for the composites with ceramic loading was evidenced. The
      stiffening effect of alphaTCP addition closely conforms to the lower Hashin
      Shtrikman bounds demonstrating that an evenly dispersed nano-filler is the least
      amenable ceramic configuration to enhance the mechanical properties of PLGA
      alphaTCP nanocomposites. The mechanical property evolution for all composite
      types in an aqueous degradation medium is dominated by material hydration which
      effects reduced material stiffness and increased specimen viscosity generating a
      core-periphery mechanical property distribution in terms of elastic modulus and
      viscoelastic phase angle. The mechanical property core-periphery structure
      correlates strongly with the core-periphery density structure characterized using
      X-ray microtomography. Hydrated regions exhibit significant reductions in elastic
      modulus and viscosity increases which are typical of elastomers.

PMID- 25063158
TI  - Fe2O3/C nanocomposites having distinctive antioxidant activity and hemolysis
      prevention efficiency.
AB  - Tailored magnetic iron oxide nanoparticles hold the prospect for nouveau
      applications in the field of biomedical technology. Herein, we report novel
      functionalities of this iron oxide system by developing a hybrid of Fe2O3/C to
      make it a multifunctional biomedical agent. A detailed magnetic study carried out
      at varying temperatures confirms the intrinsic superparamagnetic character of
      these iron oxide-carbon composites. The potential of the nanocomposite for
      biomedical applications has been evaluated by its ability to scavenge free
      radical by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Moreover, the
      nanocomposite was monitored for successful hemolysis inhibition of mammalian
      erythrocytes. The nanocomposite showed promising compatibility with the
      peripheral blood mononuclear cells (PBMC) which was visualized from trypan blue
      dye exclusion assay. Biocompatible carbon coating over the iron oxide
      nanoparticles with these functionalities has transformed it to a multifunctional
      nanoparticulate biomedical agent potential for future clinical translation. 

PMID- 25063159
TI  - EDTA assisted synthesis of hydroxyapatite nanoparticles for electrochemical
      sensing of uric acid.
AB  - Hydroxyapatite nanoparticles have been synthesized using EDTA as organic modifier
      by a simple microwave irradiation method and its application for the selective
      determination of uric acid (UA) has been demonstrated. Electrochemical behavior
      of uric acid at HA nanoparticle modified glassy carbon electrode (E-HA/GCE) has
      been investigated by electrochemical impedance spectroscopy (EIS), cyclic
      voltammetry (CV), linear sweep voltammetry (LSV) and amperometry. The E-HA
      modified electrode exhibits efficient electrochemical activity towards uric acid
      sensing without requiring enzyme or electron mediator. Amperometry studies
      revealed that the fabricated electrode has excellent sensitivity for uric acid
      with the lowest detection limit of 142 nM over a wide concentration range from 1
      * 10(-7) to 3 * 10(-5)M. Moreover, the studied E-HA modified GC electrode
      exhibits a good reproducibility and long-term stability and an admirable
      selectivity towards the determination of UA even in the presence of potential
      interferents. The analytical performance of this sensor was evaluated for the
      detection of uric acid in human urine and blood serum samples.

PMID- 25063160
TI  - Dynamic simulation and finite element analysis of the human mandible injury
      protected by polyvinyl alcohol sponge.
AB  - There have been intensive efforts to find a suitable kinetic energy absorbing
      material for helmet and bulletproof vest design. Polyvinyl alcohol (PVA) sponge
      is currently in extensive use as scaffolding material for tissue engineering
      applications. PVA can also be employed instead of commonly use kinetic energy
      absorbing materials to increase the kinetic energy absorption capacity of current
      helmet and bulletproof vest materials owing to its excellent mechanical
      properties. In this study, a combined hexahedral finite element (FE) model is
      established to determine the potential protection ability of PVA sponge in
      controlling the level of injury for gunshot wounds to the human mandible. Digital
      computed tomography data for the human mandible are used to establish a three
      dimensional FE model of the human mandible. The mechanism by which a gunshot
      injures the protected mandible by PVA sponge is dynamically simulated using the
      LS-DYNA code under two different shot angles. The stress distributions in
      different parts of the mandible and sponge after injury are also simulated. The
      modeling results regardless of shot angle reveal that the substantial amount of
      kinetic energy of the steel ball (67%) is absorbed by the PVA sponge and,
      consequently, injury severity of the mandible is significantly decreased. The
      highest energy loss (170 J) is observed for the impact at entry angle of 70
      degrees . The results suggest the application of the PVA sponge as an alternative
      reinforcement material in helmet and bulletproof vest design to absorb most of
      the impact energy and reduce the transmitted load.

PMID- 25063161
TI  - Micro/nano replication and 3D assembling techniques for scaffold fabrication.
AB  - The development of tissue engineering field entails the creation of
      micro/nanoscale features for cellular alignment and biocompatibility improvement.
      As replication techniques, hot embossing and soft lithography can be used to
      produce micro/nanoscale features on biodegradable membranes. Subsequently the
      generation of 3D scaffolds can be done by means of assembling techniques. Using
      the described techniques, high resolution of features, as small as 5 nm, can be
      achieved. Nevertheless membrane assembling must be fully studied to avoid feature
      fluctuations and even collapse of the scaffold. The present review focuses on the
      state-of-the-art in the replication techniques used to create micro/nanoscale
      features on biodegradable polymers and assembling approaches to construct
      scaffolds with the aim of exploring existing advances and limitations of the
      reported methods.

PMID- 25063162
TI  - Biomimetic alginate/polyacrylamide porous scaffold supports human mesenchymal
      stem cell proliferation and chondrogenesis.
AB  - We describe the development of alginate/polyacrylamide (ALG/PAAm) porous
      hydrogels based on interpenetrating polymer network structure for human
      mesenchymal stem cell proliferation and chondrogenesis. Three ALG/PAAm hydrogels
      at molar ratios of 10/90, 20/80, and 30/70 were prepared and characterized with
      enhanced elastic and rubbery mechanical properties, which are similar to native
      human cartilage tissues. Their elasticity and swelling properties were also
      studied under different physiological pH conditions. Finally, in vitro tests
      demonstrated that human mesenchymal stem cells could proliferate on the as
      synthesized hydrogels with improved alkaline phosphatase activities. These
      results suggest that ALG/PAAm hydrogels may be a promising biomaterial for
      cartilage tissue engineering. 

PMID- 25063163
TI  - In-vitro characterization of stress corrosion cracking of aluminium-free
      magnesium alloys for temporary bio-implant applications.
AB  - The complex interaction between physiological stresses and corrosive human body
      fluid may cause premature failure of metallic biomaterials due to the phenomenon
      of stress corrosion cracking. In this study, the susceptibility to stress
      corrosion cracking of biodegradable and aluminium-free magnesium alloys ZX50,
      WZ21 and WE43 was investigated by slow strain rate tensile testing in a simulated
      human body fluid. Slow strain rate tensile testing results indicated that each
      alloy was susceptible to stress corrosion cracking, and this was confirmed by
      fractographic features of transgranular and/or intergranular cracking. However,
      the variation in alloy susceptibility to stress corrosion cracking is explained
      on the basis of their electrochemical and microstructural characteristics. 

PMID- 25063164
TI  - Structured superparamagnetic nanoparticles for high performance mediator of
      magnetic fluid hyperthermia: synthesis, colloidal stability and biocompatibility
      evaluation.
AB  - Core-shell structures with magnetic core and metal/polymer shell provide a new
      opportunity for constructing highly efficient mediator for magnetic fluid
      hyperthermia. Herein, a facile method is described for the synthesis of
      superparamagnetic LSMO@Pluronic F127 core-shell nanoparticles. Initially, the
      surface of the LSMO nanoparticles is functionalized with oleic acid and the
      polymeric shell formation is achieved through hydrophobic interactions with oleic
      acid. Each step is optimized to get good dispersion and less aggregation. This
      methodology results into core-shell formation, of average diameter less than 40
      nm, which was stable under physiological conditions. After making a core-shell
      formulation, a significant increase of specific absorption rate (up to 300%) has
      been achieved with variation of the magnetization (<20%). Furthermore, this high
      heating capacity can be maintained in various simulated physiological conditions.
      The observed specific absorption rate is almost higher than Fe3O4. MTT assay is
      used to evaluate the toxicity of bare and core-shell MNPs. The mechanism of cell
      death by necrosis and apoptosis is studied with sequential staining of acridine
      orange and ethidium bromide using fluorescence and confocal microscopy. The
      present work reports a facile method for the synthesis of core-shell structure
      which significantly improves SAR and biocompatibility of bare LSMO MNPs,
      indicating potential application for hyperthermia.

PMID- 25063165
TI  - Biocompatible nanocrystalline natural bonelike carbonated hydroxyapatite
      synthesized by mechanical alloying in a record minimum time.
AB  - Single phase nanocrystalline biocompatible A-type carbonated hydroxyapatite (A
      cHAp) powder has been synthesized by mechanical alloying the stoichiometric
      mixture of CaCO3 and CaHPO4.2H2O powders in open air at room temperature within
      2h of milling. The A-type carbonation in HAp is confirmed by FTIR analysis.
      Structural and microstructure parameters of as-milled powders are obtained from
      both Rietveld's powder structure refinement analysis and transmission electron
      microscopy. Size and lattice strain of nanocrystalline HAp particles are found to
      be anisotropic in nature. Mechanical alloying causes amorphization of a part of
      crystalline A-cHAp which is analogous to native bone mineral. Some primary bond
      lengths of as-milled samples are critically measured. MTT [3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide] assay test reveals high percentage of cell
      viability and hence confirms the biocompatibility of the sample. The overall
      results indicate that the processed A-cHAp has a chemical composition very close
      to that of biological apatite. 

PMID- 25063166
TI  - Preparation and properties of plasma electrolytic oxidation coating on
      sandblasted pure titanium by a combination treatment.
AB  - Plasma electrolytic oxidation (PEO) is one of the most applicable methods to
      produce bioceramic coating on a dental implant and sandblasting is a primary
      technique to modify metal surface properties. This study aims to deposit
      bioceramic Ca- and P-containing coatings on sandblasted commercially pure
      titanium by PEO technique to improve its bioactive performance. The time
      dependent modified surfaces are characterized in terms of their microstructure,
      phase, chemical composition, mechanical properties and bioactivities. The results
      show that the combination-treated coating exhibits better properties than the PEO
      treated one, especially in bioactivities, as evidenced by the HA formation after
      immersion in simulated body fluid (SBF) for 5 days and the cell viability after
      seeding for 1 or 3 days. The enhancement of the modified surface is attributed to
      a combination of the mechanical sandblasting and the microplasma oxidation.

PMID- 25063167
TI  - Development of a novel aluminum-free glass ionomer cement based on
      magnesium/strontium-silicate glasses.
AB  - The effects of strontium substitution for magnesium in a novel aluminum-free
      multicomponent glass composition for glass ionomer cements (GICs) were
      investigated. A series of glass compositions were prepared based on SiO2-P2O5-CaO
      ZnO-MgO(1-X)-SrOX-CaF2 (X=0, 0.25, 0.5 and 0.75). The mechanical properties of
      GICs prepared were characterized by compressive strength, flexural strength,
      flexural modules, and microhardness. Cell proliferation was evaluated indirectly
      by CCK-8 assay using various dilutions of the cement and rat mesenchyme stem
      cells. Incorporation of strontium instead of magnesium in the glasses has a
      significant influence on setting time of the cements and the properties. All
      mechanical properties of the GICs with SrO substitution at X=0.25 were
      significantly increased, then gradually decreased with further increase of the
      amount of strontium substitution in the glass. The GIC at X=0.25, also, showed an
      improved cell viability at low doses of the cement extracts in comparison with
      other groups or control without extracts. The results of this study demonstrate
      that the glass compositions with strontium substitution at low levels can be
      successfully used to prepare aluminum-free glass ionomer cements for repair and
      regeneration of hard tissues. 

PMID- 25063168
TI  - Osteogenesis and angiogenesis properties of dental pulp cell on novel injectable
      tricalcium phosphate cement by silica doped.
AB  - beta-Tricalcium phosphate (beta-TCP) is an osteoconductive material in clinical.
      In this study, we have doped silica (Si) into beta-TCP and enhanced its bioactive
      and osteostimulative properties. To check its effectiveness, a series of Si-doped
      with different ratios were prepared to make new bioactive and biodegradable
      biocomposites for bone repair. Formation of the diametral tensile strength, ions
      released and weight loss of cements was considered after immersion. In addition,
      we also examined the behavior of human dental pulp cells (hDPCs) cultured on Si
      doped beta-TCP cements. The results showed that setting time and injectability of
      the Si-doped beta-TCP cements were decreased as the Si content was increased. At
      the end of the immersion point, weight losses of 30.1%, 36.9%, 48.1%, and 55.3%
      were observed for the cement doping 0%, 10%, 20%, and 30% Si into beta-TCP
      cements, respectively. In vitro cell experiments show that the Si-rich cements
      promote human dental pulp cell (hDPC) proliferation and differentiation. However,
      when the Si-doped in the cement is more than 20%, the amount of cells and
      osteogenesis protein of hDPCs was stimulated by Si released from Si-doped beta
      TCP cements. The degradation of beta-TCP and osteogenesis of Si gives a strong
      reason to believe that these Si-doped beta-TCP cements may prove to be promising
      bone repair materials. 

PMID- 25063169
TI  - Analytical and numerical study of diffusion-controlled drug release from
      composite spherical matrices.
AB  - We investigate, both analytically and numerically, diffusion-controlled drug
      release from composite spherical formulations consisting of an inner core and an
      outer shell of different drug diffusion coefficients. Theoretically derived
      analytical results are based on the exact solution of Fick's second law of
      diffusion for a composite sphere, while numerical data are obtained using Monte
      Carlo simulations. In both cases, and for the range of matrix parameter values
      considered in this work, fractional drug release profiles are described
      accurately by a stretched exponential function. The release kinetics obtained is
      quantified through a detailed investigation of the dependence of the two
      stretched exponential release parameters on the device characteristics, namely
      the geometrical radii of the inner core and outer shell and the corresponding
      drug diffusion coefficients. Similar behaviors are revealed by both the
      theoretical results and the numerical simulations, and approximate analytical
      expressions are presented for the dependencies. 

PMID- 25063170
TI  - Low modulus Ti-Nb-Hf alloy for biomedical applications.
AB  - beta-Type titanium alloys with a low elastic modulus are a potential strategy to
      reduce stress shielding effect and to enhance bone remodeling in implants used to
      substitute failed hard tissue. For biomaterial application, investigation on the
      mechanical behavior, the corrosion resistance and the cell response is required.
      The new Ti25Nb16Hf alloy was studied before and after 95% cold rolling (95%
      C.R.). The mechanical properties were determined by tensile testing and its
      corrosion behavior was analyzed by potentiostatic equipment in Hank's solution at
      37 degrees C. The cell response was studied by means of cytotoxicity evaluation,
      cell adhesion and proliferation measurements. The stress-strain curves showed the
      lowest elastic modulus (42GPa) in the cold worked alloy and high tensile
      strength, similar to that of Ti6Al4V. The new alloy exhibited better corrosion
      resistance in terms of open circuit potential (EOCP), but was similar in terms of
      corrosion current density (iCORR) compared to Ti grade II. Cytotoxicity studies
      revealed that the chemical composition of the alloy does not induce cytotoxic
      activity. Cell studies in the new alloy showed a lower adhesion and a higher
      proliferation compared to Ti grade II presenting, therefore, mechanical features
      similar to those of human cortical bone and, simultaneously, a good cell
      response. 

PMID- 25063171
TI  - Obtaining new composite biomaterials by means of mineralization of methacrylate
      hydrogels using the reaction-diffusion method.
AB  - The present paper describes the synthesis and characterization of a new polymeric
      biomaterial mineralized with calcium phosphate using the reaction-diffusion
      method. The scaffold of this biomaterial was a hydrogel constituted by
      biocompatible polyethylene glycol methyl ether methacrylate (PEGMEM) and 2
      (dimethylamino)ethyl methacrylate (DMAEM), which were cross-linked with N-N'
      methylenebisacrylamide (BIS). The cross-linking content of the hydrogels was
      varied from 0.25% to 15% (w/w). The gels were used as matrix where two reactants
      (Na2HPO4 and CaCl2) diffused from both ends of the gel and upon encountering
      produced calcium phosphate crystals that precipitated within the polymer matrix
      forming bands. The shape of the crystals was tuned by modifying the matrix
      porosity in such a way that when the polymer matrix was slightly reticulated the
      diffusion reaction produced round calcium phosphate microcrystals, whilst when
      the polymer matrix was highly reticulated the reaction yielded flat calcium
      phosphate crystals. Selected area electron diffraction performed on the
      nanocrystals that constitute the microcrystals showed that they were formed by
      Brushite (CaHPO4.2H2O). This new composite material could be useful in medical
      and dentistry applications such as bone regeneration, bone repair or tissue
      engineering. 

PMID- 25063172
TI  - Finite element analyses for optimization design of biodegradable magnesium alloy
      stent.
AB  - Stents made of biodegradable magnesium alloys are expected to provide a temporary
      opening into a narrowed arterial vessel until it remodels and will progressively
      disappear thereafter. Inferior mechanical properties and fast corrosion of the
      magnesium alloys are the two crucial factors that impede the clinical application
      of the magnesium alloy stents (MAS). In the present study, gradual strut width,
      addition of the peak-to-valley unit and introduction of the annealing technology
      were designed and investigated by finite element analysis in order to improve the
      performance of the MAS. Two experiments were carried out for a preliminary
      validation of the simulation. 

PMID- 25063173
TI  - Hydrophobic chitosan sponges modified by aluminum monostearate and dehydrothermal
      treatment as sustained drug delivery system.
AB  - The aim of this study is to develop hydrophobic chitosan sponges by using novel
      simple preparation technique in which hydrophobicity of chitosan was modified by
      aluminum monostearate (Alst) and dehydrothermal treatment (DHT). Alst was able to
      dissociate and to cleave stearate ion in 2% w/v lactic acid. Composite dispersion
      of chitosan and Alst (CLA) could be easily prepared by simple mixing at room
      temperature. The pH value of the CLA dispersions and particle size of the
      chitosan-Alst complex in the system comprising low chitosan concentration
      significantly increased by mixing time. The dispersions were further fabricated
      into sponges by using lyophilization technique and DHT. FT-IR spectra analysis
      indicated amidation between amino group of chitosan and carboxyl group of
      stearate side chain after DHT. Contact angle measurement was applied to evaluate
      hydrophilic/hydrophobic properties of the prepared sponges. Swelling behavior of
      the sponges was investigated in three different medium namely acetate buffer
      (pH4.0), phosphate buffer (pH7.4) and carbonate buffer (pH10.0). Drug release
      study was conducted in phosphate buffer pH7.4 at 37 degrees C by using
      asiaticoside as a model drug. Contact angle measurement revealed that addition of
      Alst and DHT enhanced the hydrophobicity of the materials. Swelling of the
      sponges decreased as Alst amount increased. Swelling behavior of the sponges was
      coincident with the release of asiaticoside in which the sponge containing higher
      Alst amount apparently exhibited the sustained release character. Release of
      asiaticoside from CLA sponges fitted well with first-order kinetic and the
      exponent value (n) in power law model indicated that the main release mechanism
      was Fickian diffusion. From this study, we found the potential of the prepared
      hydrophobic chitosan sponges for further application as drug-sustained-release,
      porous wound dressing.

PMID- 25063174
TI  - Improved antibacterial behavior of titanium surface with torularhodin-polypyrrole
      film.
AB  - The problem of microorganisms attaching and proliferating on implants and medical
      devices surfaces is still attracting interest in developing research on different
      coatings based on antibacterial agents. The aim of this work is centered on
      modifying titanium (Ti) based implants surfaces through incorporation of a
      natural compound with antimicrobial effect, torularhodin (T), by means of a
      polypyrrole (PPy) film. This study tested the potential antimicrobial activity of
      the new coating against a range of standard bacterial strains: Escherichia coli,
      Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and Pseudomonas
      aeruginosa. The morphology, physical and electrochemical properties of the
      synthesized films were assessed by SEM, AFM, UV-Vis, FTIR and cyclic voltammetry.
      In addition, biocompatibility of this new coating was evaluated using L929 mouse
      fibroblast cells. The results showed that PPy-torularhodin composite film acts as
      a corrosion protective coating with antibacterial activity and it has no harmful
      effect on cell viability. 

PMID- 25063175
TI  - Prodigiosin release from an implantable biomedical device: kinetics of localized
      cancer drug release.
AB  - This paper presents an implantable encapsulated structure that can deliver
      localized heating (hyperthermia) and controlled concentrations of prodigiosin (a
      cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)).
      Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled
      micro-channels and drug storage compartments, were fabricated along with a drug
      storing polymer produced by free radical polymerization of Poly(N
      isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate
      (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated.
      Scanning Electron Microscopy (SEM) was also used to study the heterogeneous
      porous structure of the PNIPA-based gels. The release exponents, n, of the gels
      were found to between 0.5 and 0.7. This is in the range expected for Fickian
      (n=0.5). Deviation from Fickian diffusion was also observed (n>0.5) diffusion.
      The gel diffusion coefficients were shown to vary between 2.1*10(-12)m(2)/s and
      4.8*10(-6)m(2)/s. The implications of the results are then discussed for the
      localized treatment of cancer via hyperthermia and the controlled delivery of
      prodigiosin from encapsulated PNIPA-based devices.

PMID- 25063176
TI  - In vitro and in vivo performance of bioactive Ti6Al4V/TiC/HA implants fabricated
      by a rapid microwave sintering technique.
AB  - Failure of the bone-implant interface in a joint prosthesis is a main cause of
      implant loosening. The introduction of a bioactive substance, hydroxyapatite
      (HA), to a metallic bone-implant may enhance its fixation on human bone by
      encouraging direct bone bonding. Ti6Al4V/TiC/HA composites with a reproducible
      porous structure (porosity of 27% and pore size of 6-89 MUm) were successfully
      fabricated by a rapid microwave sintering technique. This method allows the
      biocomposites to be fabricated in a short period of time under ambient
      conditions. Ti6Al4V/TiC/HA composites exhibited a compressive strength of 93 MPa,
      compressive modulus of 2.9 GPa and microhardness of 556 HV which are close to
      those of the human cortical bone. The in vitro preosteoblast MC3T3-E1 cells
      cultured on the Ti6Al4V/TiC/HA composite showed that the composite surface could
      provide a biocompatible environment for cell adhesion, proliferation and
      differentiation without any cytotoxic effects. This is among the first attempts
      to study the in vivo performance of load-bearing Ti6Al4V/TiC and Ti6Al4V/TiC/HA
      composites in a live rabbit. The results indicated that the Ti6Al4V/TiC/HA
      composite had a better bone-implant interface compared with the Ti6Al4V/TiC
      implant. Based on the microstructural features, the mechanical properties, and
      the in vitro and in vivo test results from this study, the Ti6Al4V/TiC/HA
      composites have the potential to be employed in load-bearing orthopedic
      applications.

PMID- 25063177
TI  - Wound healing potential of antibacterial microneedles loaded with green tea
      extracts.
AB  - This study evaluates the utility of an antibacterial microneedle composed of
      green tea (GT) extract and hyaluronic acid (HA), for the efficient delivery of
      GT. These microneedles have the potential to be a patient-friendly method for the
      conventional sustained release of drugs. In this study, a fabrication method
      using a mold-based technique to produce GT/HA microneedles with a maximum area of
      ~50mm(2) with antibacterial properties was used to manufacture transdermal drug
      delivery systems. Fourier transform infrared (FTIR) spectrometry was carried out
      to observe the potential modifications in the microneedles, when incorporated
      with GT. The degradation rate of GT in GT/HA microneedles was controlled simply
      by adjusting the HA composition. The effects of different ratios of GT in the HA
      microneedles were determined by measuring the release properties. In HA
      microneedles loaded with 70% GT (GT70), a continuous higher release rate was
      sustained for 72h. The in vitro cytotoxicity assays demonstrated that GT/HA
      microneedles were not generally cytotoxic to Chinese hamster ovary cells (CHO
      K1), human embryonic kidney cells (293T), and mouse muscle cells (C2C12), which
      were treated for 12 and 24h. Antimicrobial activity of the GT/HA microneedles was
      demonstrated by ~95% growth reduction of gram negative [Escherichia coli (E.
      coli), Pseudomonas putida (P. putida), and Salmonella typhimurium (S.
      typhimurium)] and gram positive bacteria [Staphylococcus aureus (S. Aureus) and
      Bacillus subtilis (B. subtilis)], with GT70. Furthermore, GT/HA microneedles
      reduced bacterial growth of infected wound sites in the skin and improved wound
      healing process of skin in rat model. 

PMID- 25063178
TI  - Synthesis and characterization of biodegradable acrylated polyurethane based on
      poly(epsilon-caprolactone) and 1,6-hexamethylene diisocyanate.
AB  - A series of biodegradable acrylic terminated polyurethanes (APUs) based on
      poly(epsilon-caprolactone) diol (PCL), aliphatic 1,6-hexamethylene diisocyanate
      (HDI) and hydroxyethyl methyl acrylate (HEMA) was synthesized as potential
      materials for hard tissue biomedical applications. PCLs with low molecular
      weights of 1000 and 2,000 g/mol were employed to provide different amounts of end
      capped urethane acrylate in APUs. To control crosslink density, a mixture of two
      different reactive diluents including mono-functional HEMA and bi-functional
      ethylene glycol dimethacrylate (EGDMA) with different weight ratios was
      incorporated into the APUs, called here PUAs. Morphological characteristics and
      mechanical properties were investigated using X-ray diffraction (XRD),
      differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA).
      DMA results indicated some degree of microphase separation between hard and soft
      segments; however, the microphase separation is more prominent for PUAs with
      higher molecular weight PCL. It was also found that the degree of crosslinking
      dominated greatly the formation of crystalline structure. PUAs with low crosslink
      density exhibited crystalline microstructure. The results also indicated that the
      mechanical properties of PUAs were governed considerably by crystalline
      microstructure, and hard segment content. All PUAs demonstrated hydrophobic
      behavior and were able to be degraded hydrolytically. The degradation process was
      closely related to the microstructure and surface tension of PUAs.

PMID- 25063179
TI  - Facile sonochemical synthesis and morphology control of CePO4 nanostructures via
      an oriented attachment mechanism: application as luminescent probe for selective
      sensing of Pb2+ ion in aqueous solution.
AB  - CePO4 nanostructures with hexagonal phase were controllably synthesized using
      Ce(NO3)3 reaction with NH4H2PO4 through a sonochemical method by simply varying
      the reaction conditions. By adding ethanol and polyethylene glycol (PEG), coral
      reef nanostructures (CRNs) were synthesized and controlling over pH caused to
      nanorods/nanowires. Oriented attachment (OA) is proposed as dominant mechanism on
      the growth of nanostructures which is in competition with Ostwald ripening (OR).
      The crystal structure and morphology of the nanostructures were characterized by
      X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM),
      respectively. The luminescent properties of CePO4 with different morphologies
      have been studied. Among the nanostructures, nanoparticles with the highest
      intensity of fluorescent have been used as luminescent probe for selective
      sensing of Pb(2+) ion in aqueous solution. 

PMID- 25063180
TI  - Study of the effect of the silver content on the structural and mechanical
      behavior of Ag-ZrCN coatings for orthopedic prostheses.
AB  - With the increase of elderly population and health problems that are arising
      nowadays, hip joint prostheses are being widely used. However, it is estimated
      that 20% of hip replacement surgeries simply fails after few years, mainly due to
      wear fatigue. Bearing this in mind, this work reports on the development of new
      coatings that are able to sustain long and innocuous life inside the patient,
      which will confer to the usual biomaterials improved physical, mechanical and
      tribological properties. In particular, the development of multifunctional
      coatings based on Ag-ZrCN, prepared by DC reactive magnetron sputtering using two
      targets, Zr and a modified Zr target, in an Ar+C2H2+N2 atmosphere. Silver pellets
      were placed in the erosion area of the alloyed Zr target in order to obtain a
      silver content up to 8 at.%. The structural results obtained by x-ray diffraction
      show that the coatings crystallize in a NaCl crystal structure typical of ZrC1
      xNx. The increase of Ag content promoted the formation of an additional a-CNx
      amorphous phase, besides a silver crystalline phase. Hardness is decreasing, as
      increasing silver content. Despite the low thicknesses, adhesion values (LC3) can
      be considered as good. Dynamic fatigue results suggest that these coatings system
      can be a real asset in terms of mechanical properties, by improving the
      performance of usual Stainless Steel 316 L biomaterials.

PMID- 25063181
TI  - Synthesis of Fe-Cu/TiO2 nanostructure and its use in construction of a sensitive
      and selective sensor for metformin determination.
AB  - A carbon paste electrode modified with Fe-Cu/TiO2 was prepared and used for low
      level determination of metformin (MET) using square wave adsorptive stripping
      voltammetry (SWAdSV). The Fe-Cu/TiO2 nanoparticle was synthesized by a modified
      sol-gel method. The surface structure and composition of nanoparticles were
      characterized by scanning electron microscopy (SEM), X-ray powder diffraction
      analysis (XRD) and N2 physisorption. Also, electrochemical properties of the
      prepared nanocomposite modified electrode were investigated by cyclic voltammetry
      and electrochemical impedance spectroscopy (EIS) techniques. Under optimized
      conditions, the modified electrode exhibited a linear response over the
      concentration range of 15 nM to 75 MUM MET, with a detection limit of 3 nM. The
      proposed sensor exhibited a high sensitivity, good selectivity and was
      successfully applied for MET determination in real samples such as human urine
      and pharmaceutical formulations.

PMID- 25063182
TI  - Fabrication of highly aligned fibrous scaffolds for tissue regeneration by
      centrifugal spinning technology.
AB  - Centrifugal spinning (C-Spin) is an emerging technology which uses centrifugal
      force to produce ultrafine fibers. Being a voltage free technique it can overcome
      the limitations of electrospinning. Owing to the unique characteristic features
      such as high surface area to volume ratio, porosity, mechanical strength and
      fiber alignment, centrifugal spun (C-spun) fibrous mat has a wide range of scope
      in various biomedical applications. Higher degree of fiber alignment can be
      effortlessly achieved by the C-Spin process. In order to prove the versatility of
      C-Spin system with respect to fiber alignment, Polycaprolactone (PCL) and gelatin
      were spun taking them as model polymers. The morphological analysis revealed that
      highly aligned ultrafine fibers with smooth surface are achieved by C-Spinning.
      Hydrophilicity, porosity and mechanical property results confirm that the C-spun
      mat is more suitable for tissue engineering applications. In vitro and in vivo
      experiments proved that the scaffolds are biocompatible and can be efficiently
      used as a wound dressing material. 

PMID- 25063183
TI  - Effects of sodium hypochlorite on Agave tequilana Weber bagasse fibers used to
      elaborate cyto and biocompatible hydrogel films.
AB  - Waste bagasse of Agave tequilana-Weber fibers treated with sodium hydroxide was
      used to elaborate hydrogel films. The bagasse was offered in an alternative use
      for the preparation of hydrogel films by phase inversion method without
      crosslinking and further purification of cellulose. The effect on the properties
      of the obtained films was studied when the chemical treatment of the agave fibers
      was changed. It was found that the resultant hydrogels showed increment in
      tensile from 40 N/mm(2) to 56 N/mm(2) with the increase of sodium hypochlorite
      concentration from 1 to 10 vol.%, respectively. With regard to biocompatibility
      properties of the hydrogel films, platelet adhesion, clotting time and protein
      adsorption were investigated. Analysis of the morphology of adherent NIH3T3
      fibroblast indicated that the projected cell area, aspect ratio and long axis
      gradually increased with the increment of sodium hypochlorite content in the
      agave treatment. It was presented that the chemical treatment affects cell
      adhesion and morphology and lignin content remains in the brown fibers.

PMID- 25063184
TI  - Healing of critical-size segmental defects in rat femora using strong porous
      bioactive glass scaffolds.
AB  - The repair of structural bone defects such as segmental defects in the long bones
      of the limbs is a challenging clinical problem. In this study, the capacity of
      silicate (13-93) and borate (13-93B3) bioactive glass scaffolds (porosity=47-50%)
      to heal critical-size segmental defects in rat femurs was evaluated and compared
      with autografts. Defects were implanted with 13-93 and 13-93B3 scaffolds with a
      grid-like microstructure (compressive strength=86 MPa and 40 MPa, respectively),
      13-93B3 scaffolds with an oriented microstructure (compressive strength=32 MPa)
      and autografts using intramedullary fixation. Twelve weeks post-implantation, the
      defects were harvested and evaluated using histomorphometric analysis. The
      percentage of new bone in the defects implanted with the three groups of glass
      scaffolds (25-28%) and the total von Kossa-positive area (32-38%) were not
      significantly different from the autografts (new bone=38%; von Kossa-positive
      area=40%) (p>0.05). New blood vessel area in the defects implanted with the glass
      scaffolds (4-8%) and the autografts (5%) showed no significant difference among
      the four groups. New cartilage formed in the 13-93 grid-like scaffolds (18%) was
      significantly higher than in 13-93B3 grid-like scaffolds (8%) and in the
      autografts (8%) (p=0.02). The results indicate that these strong porous bioactive
      glass scaffolds are promising synthetic implants for structural bone repair.

PMID- 25063186
TI  - Hypothalamic and Limbic System Changes in Huntington's Disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded
      CAG repeat in the huntingtin gene. Today, the clinical diagnosis of the disease
      requires unequivocal signs of typical motor disturbances, which is thought to be
      due to pathology in the striatum of the basal ganglia. Increasing numbers of
      studies have emphasized that also non-motor symptoms and signs are common and
      occur early in HD. These include psychiatric disturbances and cognitive
      impairment as well as sleep disturbances with disrupted circadian rhythm,
      autonomic dysfunction and metabolic changes. Several of the non-motor features
      may be results of dysfunction of the hypothalamus and the limbic system, which
      are interconnected structures central in the regulation of emotion, sleep and
      metabolism. In fact, recent studies using postmortem tissue, magnetic resonance
      imaging and positron emission tomography have shown that hypothalamic and limbic
      system changes occur early in clinical HD. This review summarizes the current
      state of knowledge in this area based on clinical studies as well as experiments
      in animal models of the disease and establishes that hypothalamic and limbic
      system changes are part of the HD pathology. 

PMID- 25063185
TI  - Proteomic analysis of fibroblastema formation in regenerating hind limbs of
      Xenopus laevis froglets and comparison to axolotl.
AB  - BACKGROUND: To gain insight into what differences might restrict the capacity for
      limb regeneration in Xenopus froglets, we used High Performance Liquid
      Chromatography (HPLC)/double mass spectrometry to characterize protein expression
      during fibroblastema formation in the amputated froglet hindlimb, and compared
      the results to those obtained previously for blastema formation in the axolotl
      limb. RESULTS: Comparison of the Xenopus fibroblastema and axolotl blastema
      revealed several similarities and significant differences in proteomic profiles.
      The most significant similarity was the strong parallel down regulation of muscle
      proteins and enzymes involved in carbohydrate metabolism. Regenerating Xenopus
      limbs differed significantly from axolotl regenerating limbs in several ways:
      deficiency in the inositol phosphate/diacylglycerol signaling pathway, down
      regulation of Wnt signaling, up regulation of extracellular matrix (ECM) proteins
      and proteins involved in chondrocyte differentiation, lack of expression of a key
      cell cycle protein, ecotropic viral integration site 5 (EVI5), that blocks
      mitosis in the axolotl, and the expression of several patterning proteins not
      seen in the axolotl that may dorsalize the fibroblastema. CONCLUSIONS: We have
      characterized global protein expression during fibroblastema formation after
      amputation of the Xenopus froglet hindlimb and identified several differences
      that lead to signaling deficiency, failure to retard mitosis, premature
      chondrocyte differentiation, and failure of dorsoventral axial asymmetry. These
      differences point to possible interventions to improve blastema formation and
      pattern formation in the froglet limb.

PMID- 25063188
TI  - The Appointment of a Huntington's Disease Nurse Specialist has Reduced Admission
      Rate and Improved Admission Quality.
AB  - We aimed to determine if the appointment of a Huntington's disease (HD) nurse
      specialist has influenced inpatient admission rates and admission quality at
      Auckland Hospital. We collated HD inpatient admission data for the 32 months
      before and after her appointment and compared the quality of cognition, mood,
      speech/swallowing and safety assessments between admissions where the nurse was
      and was not involved. After the appointment of the HD nurse there was a 51%
      reduction in average monthly HD admission rates (p = 0.0009). HD admissions
      specifically related to HD decreased by 54% (p = 0.005). There was also an
      improvement in the quality of admissions. 

PMID- 25063187
TI  - Functional Differences Between Direct and Indirect Striatal Output Pathways in
      Huntington's Disease.
AB  - There is morphological evidence for differential alterations in striatal medium
      sized spiny neurons (MSNs) giving rise to the direct and indirect output pathways
      in Huntington's disease (HD). MSNs of the indirect pathway appear to be
      particularly vulnerable and markers for these neurons are lost early in
      postmortem brains and in genetic mouse models. In contrast, MSNs of the direct
      pathway appear to be relatively spared in the early stages. Because of the great
      morphological and electrophysiological similarities between MSNs of these
      pathways, until recently it was difficult to tease apart their functional
      alterations in HD models. The recent use of the enhanced green fluorescent
      protein gene as a reporter to identify dopamine D1 (direct pathway) and D2
      (indirect pathway) receptor-expressing MSNs has made it possible to examine
      synaptic function in each pathway. The outcomes of such studies demonstrate
      significant time-dependent changes in the balance of excitatory and inhibitory
      inputs to both direct and indirect pathway MSNs in HD and emphasize early
      increases in both excitatory and inhibitory inputs to direct pathway MSNs. There
      also is a strong influence of alterations in dopamine modulation that possibly
      cause some of the changes in excitatory and inhibitory synaptic transmission in
      the HD models. These changes will markedly alter the output structures, the GPi
      and the SNr. In the future, the use of combined optogenetics with identified
      neurons in each pathway will help unravel the next set of questions about how the
      output nuclei are affected in HD. 

PMID- 25063189
TI  - Neuroleptic Malignant Syndrome Induced by Olanzapine in a Patient with
      Huntington's Disease.

PMID- 25063190
TI  - The Patient Education Program for Huntington's Disease (PEP-HD).
AB  - The goal of the Patient Education Program for Huntington's disease is to improve
      quality of life for patients and caregivers, to educate and train them in order
      to develop coping strategies to deal with psychosocial stressors. The program was
      derived from a standardized evidence-based program for Parkinson's disease. This
      pilot study assessed the feasibility of the program in Huntington's disease.
      Forty manifest patients with 28 caregivers and 19 premanifest carriers with 14
      partners participated. Assessments for depression and anxiety, psychosocial
      burden, need for help, quality of life, coping, behavioral, motor and cognitive
      status were performed. After program completion, significant improvement of
      behavioral symptoms and anxiety was found for manifest HD patients, and they used
      a less passive coping style and more social support. Their caregivers reported
      less psychosocial burden. Premanifest carriers and their partners improved their
      coping by seeking social support more often. This pilot study demonstrated the
      feasibility of the program in Huntington's disease, especially in the manifest
      stage of the disease. Further research to assess the effectiveness of the program
      seems warranted. 

PMID- 25063191
TI  - Plasma 8-hydroxy-2'-deoxyguanosine Levels in Huntington Disease and Healthy
      Controls Treated with Coenzyme Q10.
AB  - We analyzed plasma 8OHdG concentrations in 20 individuals enrolled in the Pre
      2CARE study before and after treatment with CoQ. Treatment resulted in a mean
      reduction in 8OHdG of 2.9 +/- 2.9 pg/ml for the cohort (p = 0.0003) and 3.0 +/-
      2.6 pg/ml, for the HD group (p = 0.002). Baseline 8OHdG levels were not different
      between individuals with HD and controls (19.3 +/- 3.2 pg/ml vs. 19.5 +/- 4.7
      pg/ml, p = 0.87) though baseline CoQ levels were elevated in HD compared with
      controls (p < 0.001). CoQ treatment reduces plasma 8OHdG and this reduction may
      serve as a marker of pharmacologic activity of CoQ in HD. 

PMID- 25063192
TI  - Visual Working Memory Impairment in Premanifest Gene-Carriers and Early
      Huntington's Disease.
AB  - Working memory deficits have been found in Huntington's disease (HD) and in a
      small group of premanifest (PreHD) gene-carriers. However, the nature and extent
      of these deficits are unknown. In a large cross-sectional study, we aimed to
      determine the degree of visuospatial working memory dysfunction across multiple
      stages of HD. Specifically, visuospatial working memory capacity and response
      times across various degrees of difficulty were examined, as well as the
      relationship between visuospatial working memory and motor dysfunction. We
      examined 62 PreHD-A gene-carriers (>10.8 years from estimated disease onset), 58
      PreHD-B gene-carriers (<10.8 years from estimated disease onset), 77 stage-1 HD
      patients (HD1), 44 stage-2 HD patients (HD2), and 122 healthy controls.
      Participants viewed coloured squares (in sets of 3, 5 and 7) on a screen and were
      to decide whether on a subsequent screen the encircled square has changed colour.
      Accuracy and response times were recorded. Compared to controls, significant
      group differences in visuospatial working memory capacity (accuracy) were seen in
      PreHD-B, HD1 and HD2 groups across the difficulty levels. Significant group
      differences on response times were found for all groups (PreHD-A to HD2) compared
      to controls; the most difficult level producing the only group difference in
      speed between PreHD-A and controls. Accuracy and speed were positively correlated
      only in the HD groups. These findings suggest that visuospatial working memory
      impairments are detectable in both premanifest and manifest HD; the manifest HD
      showed evidence for a "worse-worse phenomenon" whereby reductions were present in
      both motor speed and accuracy. 

PMID- 25063193
TI  - International trade of health services: global trends and local impact.
AB  - Globalization is a key challenge facing health policy-makers. A significant
      dimension of this is trade in health services. Traditionally, the flow of health
      services exports went from North to South, with patients travelling in the
      opposite direction. This situation is changing and a number of papers have
      discussed the growth of health services exports from Southern countries in its
      different dimensions. Less attention has been paid to assess the real scope of
      this trade at the global level and its potential impact at the local level. Given
      the rapid development of this area, there are little empirical data. This paper
      therefore first built an estimate of the global size and of the growth trend of
      international trade in health services since 1997, which is compared with several
      country-based studies. The second purpose of the paper is to demonstrate the
      significant economic impact of this trade at the local level for the exporting
      country. We consider the case of health providers in the South-Mediterranean
      region for which the demand potential, the economic effects and the consequence
      for the health system are presented. These issues lead to the overall conclusion
      that different policy options would be appropriate, in relation to the nature of
      the demand. 

PMID- 25063194
TI  - Increased oxidative metabolism and myoglobin expression in zebrafish muscle
      during chronic hypoxia.
AB  - Fish may be extremely hypoxia resistant. We investigated how muscle fibre size
      and oxidative capacity in zebrafish (Danio rerio) adapt during severe chronic
      hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant
      hypoxia (CCH) (10% air/90%N2 saturated water). We analyzed cross-sectional area
      (CSA), succinate dehydrogenase (SDH) activity, capillarization, myonuclear
      density, myoglobin (Mb) concentration and Mb mRNA expression of high and low
      oxidative muscle fibres. After 3 weeks of CCH, CSA, SDH activity, Mb
      concentration, capillary and myonuclear density of both muscle fibre types were
      similar as under normoxia. In contrast, staining intensity for Mb mRNA of hypoxic
      high oxidative muscle fibres was 94% higher than that of normoxic controls
      (P<0.001). Between 3 and 6 weeks of CCH, CSA of high and low oxidative muscle
      fibres increased by 25 and 30%, respectively. This was similar to normoxic
      controls. Capillary and myonuclear density were not changed by CCH. However, in
      high oxidative muscle fibres of fish maintained under CCH, SDH activity, Mb
      concentration as well as Mb mRNA content were higher by 86%, 138% and 90%,
      respectively, than in muscle fibres of fish kept under normoxia (P<0.001). In low
      oxidative muscle fibres, SDH activity, Mb and Mb mRNA content were not
      significantly changed. Under normoxia, the calculated interstitial oxygen tension
      required to prevent anoxic cores in muscle fibres (PO2crit) of high oxidative
      muscle fibres was between 1.0 and 1.7 mmHg. These values were similar at 3 and 6
      weeks CCH. We conclude that high oxidative skeletal muscle fibres of zebrafish
      continue to grow and increase oxidative capacity during CCH. Oxygen supply to
      mitochondria in these fibres may be facilitated by an increased Mb concentration,
      which is regulated by an increase in Mb mRNA content per myonucleus. 

PMID- 25063195
TI  - Boc modifies the spectrum of holoprosencephaly in the absence of Gas1 function.
AB  - Holoprosencephaly is a heterogeneous developmental malformation of the central
      nervous system characterized by impaired forebrain cleavage, midline facial
      anomalies and wide phenotypic variation. Indeed, microforms represent the mildest
      manifestation, associated with facial anomalies but an intact central nervous
      system. In many cases, perturbations in sonic hedgehog signaling are responsible
      for holoprosencephaly. Here, we have elucidated the contribution of Gas1 and an
      additional hedgehog co-receptor, Boc during early development of the craniofacial
      midline, by generating single and compound mutant mice. Significantly, we find
      Boc has an essential role in the etiology of a unique form of lobar
      holoprosencephaly that only occurs in conjunction with combined loss of Gas1.
      Whilst Gas1(-/-) mice have microform holoprosencephaly characterized by a single
      median maxillary central incisor, cleft palate and pituitary anomalies, Boc(-/-)
      mice have a normal facial midline. However, Gas1(-/-); Boc(-/-) mutants have
      lobar holoprosencephaly associated with clefting of the lip, palate and tongue,
      secondary to reduced sonic hedgehog transduction in the central nervous system
      and face. Moreover, maxillary incisor development is severely disrupted in these
      mice, arresting prior to cellular differentiation as a result of apoptosis in the
      odontogenic epithelium. Thus, Boc and Gas1 retain an essential function in these
      tooth germs, independent of their role in midline development of the central
      nervous system and face. Collectively, this phenotype demonstrates both
      redundancy and individual requirements for Gas1 and Boc during sonic hedgehog
      transduction in the craniofacial midline and suggests BOC as a potential digenic
      locus for lobar holoprosencephaly in human populations. 

PMID- 25063196
TI  - MiR-153 targets the nuclear factor-1 family and protects against teratogenic
      effects of ethanol exposure in fetal neural stem cells.
AB  - Ethanol exposure during pregnancy is an established cause of birth defects,
      including neurodevelopmental defects. Most adult neurons are produced during the
      second trimester-equivalent period. The fetal neural stem cells (NSCs) that
      generate these neurons are an important but poorly understood target for
      teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of
      teratogenesis. We previously showed that ethanol decreased, while nicotine
      increased miR-153 expression in NSCs. To understand the role of miR-153 in the
      etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo,
      by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs
      and gene networks as important miR-153 targets. Moreover, miR-153 over-expression
      prevented neuronal differentiation without altering neuroepithelial cell survival
      or proliferation. Analysis of 3'UTRs and in utero over-expression of pre-miR-153
      in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib,
      as direct targets of miR-153. In utero ethanol exposure resulted in a predicted
      expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR
      153 over-expression prevented, and partly reversed, the effects of ethanol
      exposure on miR-153 target transcripts. Varenicline, a partial nicotinic
      acetylcholine receptor agonist that, like nicotine, induces miR-153 expression,
      also prevented and reversed the effects of ethanol exposure. These data
      collectively provide evidence for a role for miR-153 in preventing premature NSC
      differentiation. Moreover, they provide the first evidence in a preclinical model
      that direct or pharmacological manipulation of miRNAs have the potential to
      prevent or even reverse effects of a teratogen like ethanol on fetal development.

PMID- 25063197
TI  - Autocrine signaling is a key regulatory element during osteoclastogenesis.
AB  - Osteoclasts are responsible for bone destruction in degenerative, inflammatory
      and metastatic bone disorders. Although osteoclastogenesis has been well
      characterized in mouse models, many questions remain regarding the regulation of
      osteoclast formation in human diseases. We examined the regulation of human
      precursors induced to differentiate and fuse into multinucleated osteoclasts by
      receptor activator of nuclear factor kappa-B ligand (RANKL). High-content single
      cell microscopy enabled the time-resolved quantification of both the population
      of monocytic precursors and the emerging osteoclasts. We observed that prior to
      induction of osteoclast fusion, RANKL stimulated precursor proliferation, acting
      in part through an autocrine mediator. Cytokines secreted during
      osteoclastogenesis were resolved using multiplexed quantification combined with a
      Partial Least Squares Regression model to identify the relative importance of
      specific cytokines for the osteoclastogenesis outcome. Interleukin 8 (IL-8) was
      identified as one of RANKL-induced cytokines and validated for its role in
      osteoclast formation using inhibitors of the IL-8 cognate receptors CXCR1 and
      CXCR2 or an IL-8 blocking antibody. These insights demonstrate that autocrine
      signaling induced by RANKL represents a key regulatory component of human
      osteoclastogenesis. 

PMID- 25063198
TI  - Deafness in occludin-deficient mice with dislocation of tricellulin and
      progressive apoptosis of the hair cells.
AB  - Occludin is the first identified protein in the tight junction (TJ), but its
      function has remained for the most part obscure. TJs have been demonstrated to
      play important roles in the inner ear function, and occludin is expressed in all
      the epithelial TJs in the inner ear. Thus, we examined the inner ears of occludin
      deficient (Occ(-/-)) mice. Although inner ears initially developed normally in
      Occ(-/-) mice, apoptosis occurs in hair cells in the organ of Corti around day 12
      after birth, and deafness develops. Since hair cell degeneration was not observed
      in cochlear explant cultures of Occ(-/-) mice, environmental changes were
      considered to be the trigger of cell death. As for the vestibular system, both
      the morphologies and functions are normal in Occ(-/-) mice. These phenotypes of
      Occ(-/-) mice are very similar with those of claudin-14 or claudin-9 deficient
      mice, leading us to speculate on the existence of imbalance induced by TJ
      abnormalities, such as localized ionic components. Moreover, the occludin
      deficiency led to dislocalization of tricellulin, a gene responsible for human
      deafness DFNB49. The deafness in Occ(-/-) mice may be due to this dislocalization
      of tricellulin. 

PMID- 25063199
TI  - Molecular cloning of ion channels in Felis catus that are related to periodic
      paralyses in man: a contribution to the understanding of the genetic
      susceptibility to feline neck ventroflexion and paralysis.
AB  - Neck ventroflexion in cats has different causes; however, the most common is the
      hypokalemia associated with flaccid paralysis secondary to chronic renal failure.
      In humans, the most common causes of acute flaccid paralysis are hypokalemia
      precipitated by thyrotoxicosis and familial forms linked to mutations in sodium,
      potassium, and calcium channel genes. Here, we describe the sequencing and
      analysis of skeletal muscle ion channels in Felis catus that could be related to
      periodic paralyses in humans, contributing to the understanding of the genetic
      susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA
      from eleven cats, including five animals that were hyperthyroid with hypokalemia,
      although only one presented with muscle weakness, and six healthy control
      domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12,
      KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several
      polymorphic variants. Upon comparative alignment with other genomes, we found
      that Felis catus provides evidence for a high genomic conservation of ion channel
      sequences. Although we hypothesized that neck ventroflexion in cats could be
      associated with a thyrotoxic or familial periodic paralysis channel mutation, we
      did not identify any previously detected human channel mutation in the
      hyperthyroid cat presenting hypokalemia. However, based on the small number of
      affected cats in this study, we cannot yet rule out this molecular mechanism.
      Notwithstanding, hyperthyroidism should still be considered as a differential
      diagnosis in hypokalemic feline paralysis. 

PMID- 25063200
TI  - Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and
      glycolate, support mitochondrial membrane potential and neuronal survival.
AB  - Parkinson's disease is associated with mitochondrial decline in dopaminergic
      neurons of the substantia nigra. One of the genes linked with the onset of
      Parkinson's disease, DJ-1/PARK7, belongs to a novel glyoxalase family and
      influences mitochondrial activity. It has been assumed that glyoxalases fulfill
      this task by detoxifying aggressive aldehyde by-products of metabolism. Here we
      show that supplying either D-lactate or glycolate, products of DJ-1, rescues the
      requirement for the enzyme in maintenance of mitochondrial potential. We further
      show that glycolic acid and D-lactic acid can elevate lowered mitochondrial
      membrane potential caused by silencing PINK-1, another Parkinson's related gene,
      as well as by paraquat, an environmental toxin known to be linked with
      Parkinson's disease. We propose that DJ-1 and consequently its products are
      components of a novel pathway that stabilizes mitochondria during cellular
      stress. We go on to show that survival of cultured mesencephalic dopaminergic
      neurons, defective in Parkinson's disease, is enhanced by glycolate and D
      lactate. Because glycolic and D-lactic acids occur naturally, they are therefore
      a potential therapeutic route for treatment or prevention of Parkinson's disease.

PMID- 25063201
TI  - Blockage of tissue factor ameliorates the lesion of laser-induced choroidal
      neovascularization in mice.
AB  - Choroidal neovascularization (CNV) occurs as a result of age-related macular
      degeneration (AMD) and causes severe vision loss among elderly patients. High
      expression of tissue factor (TF) was found in the retinas of AMD patients. In
      this study, we used anti-TF monoclonal antibody to test the effect of the TF
      blockage on experimental CNV induced by laser photocoagulation of retina in mice.
      Anti-TF monoclonal antibody or vehicle was administered intravitreally at day 1,
      2 or 3 after laser application. We found that TF expression increased, and
      reached the peak at the 3rd week after the after laser application. Anti-TF
      monoclonal antibody can predominantly decrease the expression of TF, VEGF and
      F4/80, and reduced the area of CNV. Anti-TF monoclonal antibody also decreased
      incidence of CNV and leakage area. There were no pathological changes in the
      liver, heart, brain or kidney tissue. We conclude that TF plays an important role
      in CNV and anti-TF monoclonal antibody significantly decreases CNV in mouse model
      and anti-TF monoclonal antibody may have therapeutic potential in AMD. 

PMID- 25063203
TI  - Important impacts of intestinal bacteria on utilization of dietary amino acids in
      pigs.
AB  - Bacteria in pig intestine can actively metabolize amino acids (AA). However,
      little research has focused on the variation in AA metabolism by bacteria from
      different niches. This study compared the metabolism of AA by microorganisms
      derived from the lumen and epithelial wall of the pig small intestine, aiming to
      test the hypothesis that the metabolic profile of AA by gut microbes was niche
      specific. Samples from the digesta, gut wall washes and gut wall of the jejunum
      and ileum were used as inocula. Anaerobic media containing single AA were used
      and cultured for 24 h. The 24-h culture served as inocula for the subsequent 30
      times of subcultures. Results showed that for the luminal bacteria, all AA
      concentrations except phenylalanine in the ileum decreased during the 24-h in
      vitro incubation with a increase of ammonia concentration, while 4 AA (glutamate,
      glutamine, arginine and lysine) in the jejunum decreased, with the disappearance
      rate at 60-95 %. For tightly attached bacteria, all AA concentrations were
      generally increased during the first 12 h and then decreased coupled with first a
      decrease and then an increase of ammonia concentration, suggesting a synthesis
      first and then a catabolism pattern. Among them, glutamate in both segments,
      histidine in the jejunum and lysine in the ileum increased significantly during
      the first 12 h and then decreased at 24 h. The concentrations of glutamine and
      arginine did not change during the first 12 h, but significantly decreased at 24
      h. Jejunal lysine and ileal threonine were increased for the first 6 or 12 h. For
      the loosely attached bacteria, there was no clear pattern for the entire AA
      metabolism. However, glutamate, methionine and lysine in the jejunum decreased
      after 24 h of cultivation, while glutamine and threonine in the jejunum and
      glutamine and lysine in the ileum increased in the first 12 h. During subculture,
      AA metabolism, either utilization or synthesis, was generally decreased with
      disappearance rate around 20-40 % for most of AA and negligible for branch
      chained AA (BCAA). However, the disappearance rate of lysine in each group was
      around 90 % throughout the subculture, suggesting a high utilization of lysine by
      bacteria from all three compartments. Analysis of the microbial community during
      the 24-h in vitro cultivation revealed that bacteria composition in most AA
      cultures varied between different niches (lumen and wall-adherent fractions) in
      the jejunum, while being relatively similar in the ileum. However, for isoleucine
      and leucine cultures, bacteria diversity was similar between the luminal fraction
      and tightly attached fraction, but significantly higher than in the loosely
      attached fraction. For glutamine and valine cultures, bacteria diversity was
      similar between the luminal and loosely attached fractions, but lower than that
      of tightly attached bacteria. After 30 subcultures, bacteria diversity in
      arginine, valine, glutamine, and leucine cultures varied between niches in the
      jejunum while being relatively stable in the ileum, consistent with those in the
      24-h in vitro cultures. The findings may suggest that luminal bacteria tended to
      utilize free AA, while tightly attached adherent bacteria seemed in favor of AA
      synthesis, and that small intestinal microbes contributed little to BCAA
      metabolism. 

PMID- 25063204
TI  - Leucine stimulates ASCT2 amino acid transporter expression in porcine jejunal
      epithelial cell line (IPEC-J2) through PI3K/Akt/mTOR and ERK signaling pathways.
AB  - Leucine has been shown to influence intestinal protein metabolism, cell
      proliferation and migration. Furthermore, our previous study demonstrated that
      branched-chain amino acids could modulate the intestinal amino acid and peptide
      transporters in vivo. As the possible mechanisms are still largely unknown, in
      the present work, we studied the transcriptional and translational regulation of
      leucine on amino acid transporter production in IPEC-J2 cells and the signaling
      pathways involved. Treatment of IPEC-J2 cells with 7.5 mM leucine enhanced the
      mRNA expression of the Na(+)-neutral AA exchanger 2 (ASCT2) and 4F2 heavy chain
      (4F2hc) and caused an increase in ASCT2 protein expression. Leucine also
      activated phosphorylation of 4E-BP1 and eIF4E through the phosphorylation of
      mTOR, Akt and ERK signaling pathways in IPEC-J2 cells. Pre-treatment of IPEC-J2
      cells with inhibitors of mTOR and Akt (rapamycin and wortmannin) or an inhibitor
      of ERK (PD098059) for 30 min before leucine treatment attenuated the positive
      effect of leucine in enhancing the protein abundance of ASCT2. These results
      demonstrate that leucine could up-regulate the expression of the amino acid
      transporters (ASCT2) through transcriptional and translational regulation by ERK
      and PI3K/Akt/mTOR activation.

PMID- 25063205
TI  - Whey protein supplementation accelerates satellite cell proliferation during
      recovery from eccentric exercise.
AB  - Human skeletal muscle satellite cells (SCs) are essential for muscle regeneration
      and remodeling processes in healthy and clinical conditions involving muscle
      breakdown. However, the potential influence of protein supplementation on post
      exercise SC regulation in human skeletal muscle has not been well investigated.
      In a comparative human study, we investigated the effect of hydrolyzed whey
      protein supplementation following eccentric exercise on fiber type-specific SC
      accumulation. Twenty-four young healthy subjects received either hydrolyzed whey
      protein + carbohydrate (whey, n = 12) or iso-caloric carbohydrate (placebo, n =
      12) during post-exercise recovery from 150 maximal unilateral eccentric
      contractions. Prior to and 24, 48 and 168 h post-exercise, muscle biopsies were
      obtained from the exercise leg and analyzed for fiber type-specific SC content.
      Maximal voluntary contraction (MVC) and serum creatine kinase (CK) were evaluated
      as indices of recovery from muscle damage. In type II fiber-associated SCs, the
      whey group increased SCs/fiber from 0.05 [0.02; 0.07] to 0.09 [0.06; 0.12] (p <
      0.05) and 0.11 [0.06; 0.16] (p < 0.001) at 24 and 48 h, respectively, and
      exhibited a difference from the placebo group (p < 0.05) at 48 h. The whey group
      increased SCs/myonuclei from 4 % [2; 5] to 10 % [4; 16] (p < 0.05) at 48 h,
      whereas the placebo group increased from 5 % [2; 7] to 9 % [3; 16] (p < 0.01) at
      168 h. MVC decreased (p < 0.001) and muscle soreness and CK increased (p <
      0.001), irrespective of supplementation. In conclusion, whey protein
      supplementation may accelerate SC proliferation as part of the regeneration or
      remodeling process after high-intensity eccentric exercise. 

PMID- 25063206
TI  - Endoscopic quality indicators for esophagogastroduodenoscopy in gastric cancer
      screening.
AB  - BACKGROUND: Quality indicators of screening esophagogastroduodenoscopy are
      essential to improve the detection rate of gastric cancer. However, a reliable,
      practical indicator of the performance of endoscopists in screening
      esophagogastroduodenoscopy has not yet been identified. AIMS: We aimed to
      identify quality indicators of esophagogastroduodenoscopy for the detection of
      early gastric neoplasms, including gastric dysplasia and early gastric cancer,
      focusing on the endoscopic findings. METHODS: The records of 54,889 individuals
      who underwent esophagogastroduodenoscopy for gastric cancer screening at the
      Yonsei University Severance Hospital Health Promotion Center, Seoul, Korea,
      between February 2006 and July 2013 were analyzed. The detection rates for
      various gastric lesions including early gastric neoplasms were analyzed for each
      endoscopist. RESULTS: Gastric dysplasia, early gastric cancer, and advanced
      gastric cancer were detected in 97 (0.18 %), 54 (0.10 %), and 21 (0.04 %) of
      54,889 individuals, respectively. Multivariate analysis showed that the detection
      rates of gastric subepithelial lesions and gastric diverticuli were independent
      factors associated with the detection rate of early gastric neoplasms (regression
      coefficients of 0.096 and 0.532, respectively). A quality score formula was
      deduced using these regression coefficients to predict the ability of an
      endoscopist to detect early gastric neoplasms. A trend test confirmed that the
      group of endoscopists with a higher quality score showed a significantly higher
      rate of early gastric neoplasm detection (P < 0.001). CONCLUSIONS: The detection
      rates of gastric subepithelial lesions and gastric diverticuli are well
      correlated with that of early gastric neoplasms. In addition, the proposed
      quality scoring system could be a good quality indicator for the detection of
      early gastric neoplasms.

PMID- 25063207
TI  - Protective effect of hesperidin against lung injury induced by intestinal
      ischemia/reperfusion in adult albino rats: histological, immunohistochemical and
      biochemical study.
AB  - Hesperidin is a naturally common flavonoid. It is an abundant and cheap by
      product of citrus cultivation. It is reported to have antioxidative, anti
      inflammatory and anticarcinogenic effects. This work was performed to investigate
      the possible protective role of hesperidin in ameliorating the effect of
      experimentally induced intestinal ischemia/reperfusion injury (I/R) on lung
      tissue, histologically, immunohistochemically and biochemically. Thirty male
      Wistar adult albino rats were randomized into three groups named: group I
      (control group); group II (I/R); and group III (I/R with hesperidin). Intestinal
      I/R was induced by occluding the superior mesenteric artery for 60 min, followed
      by 120 min of reperfusion period. Animals were given hesperidin orally 1h before
      the onset of ischemia. At the end of the reperfusion period the lung tissues were
      extracted for histopathological examination and immunohistochemical detection of
      the distribution of inducible nitric oxide synthase (iNOS). Pulmonary edema was
      evaluated by lung tissue wet/dry weight ratios. The levels of malondialdehyde
      (MDA, a biomarker of oxidative damage), myeloperoxidase (MPO, an index of the
      degree of neutrophil accumulation) and glutathione (GSH, a biomarker of
      protective oxidative injury) were also determined in all dissected tissues.
      Pretreatment with hesperidin (in group III) alleviated lung morphological changes
      noticed in I/R group and the levels of MDA and MPO were significantly decreased
      whereas those of GSH were significantly increased. Immunohistochemical study
      revealed a significant decrease in the iNOS. Hesperidin also significantly
      alleviated the formation of pulmonary edema as evidenced by the decreased organ
      wet/dry weight ratios. Hesperidin exerts a protective effect against lung damage
      induced by intestinal I/R injury in rats by reducing oxidative stress.

PMID- 25063208
TI  - Distribution of endocrine cells in the digestive tract of Alligator sinensis
      during the active and hibernating period.
AB  - The digestive tract is the largest endocrine organ in the body; the distribution
      pattern of endocrine cells varies with different pathological and physiological
      states. The aim of the present study was to investigate the distributed density
      of 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SS) and vasoactive
      intestinal peptide (VIP) immunoreactive (IR) cells in the digestive tract of
      Alligator sinensis during the active and hibernating period by
      immunohistochemical (IHC) method. The results indicated that 5-HT-IR cells were
      distributed throughout the entire digestive tract, which were most predominant in
      duodenum and jejunum. The density increased significantly in stomach and duodenum
      during hibernation. GAS-IR cells were limited in small stomach and small
      intestine. The density decreased significantly in small stomach during
      hibernation, while increased in duodenum. What's more, most of the endocrine
      cells in duodenum were generally spindle shaped with long cytoplasmic processes
      ending in the lumen during hibernation. SS-IR cells were limited in stomach and
      small stomach. The density increased in stomach while decreased in small stomach
      during hibernation, meanwhile, fewer IR cells occurred in small intestine. VIP-IR
      cells occurred in stomach and small stomach. The density decreased in small
      stomach, while increased in stomach during hibernation. These results indicated
      that the endocrine cells in different parts of digestive tract varied differently
      during hibernation, their changes were adaptive response to the hibernation.

PMID- 25063209
TI  - Apoptotic effects of the 'designer drug' methylenedioxypyrovalerone (MDPV) on the
      neonatal mouse brain.
AB  - The designer drug of cathinone family, methylenedioxypyrovalerone (MDPV), is a
      cheap and frequently used psychoactive drug of abuse. However, its mechanism of
      action, particularly its potential detrimental effect on the developing brain, is
      largely unknown, despite the fact that pregnant females may occur among the
      users. The objective of our study was to identify the brain areas sensitive for a
      possible apoptotic effect of the widely abused MDPV on the developing brain. To
      this end, we used a mouse model which can be compared with the human fetus of
      third trimester, considering the developmental stage of the brain. Litters of 7
      day-old C57BL/6J mice were treated either with i.p. injection of 10mg/kg b.wt.of
      MDPV or vehicle (saline), and sacrificed after 24h. Similar dose of MDPV enhanced
      locomotor activity of pups. The brains were processed for anti-caspase 3 (Casp3)
      immunohistochemistry and the apoptotic cells were identified and counted. We
      found prominent increase in the number of apoptotic cells in the piriform cortex,
      retrosplenial area, hippocampus CA1 and nucleus accumbens, whereas the overall
      density of cells did not change significantly in these regions. The neurons of
      the nucleus accumbens appeared to be especially sensitive to MDPV: Casp3
      immunoreactive cells marked out the core and shell regions of the accumbens.
      Highest percentage of apoptotic cells as compared to total cell density was also
      found in the nucleus accumbens. However, we did not observe the same effect on
      the brain of adult mice. Thus, MDPV did not seem to increase apoptosis in the
      mature nervous system. The results are in agreement with the assumption that
      cathinones (in particular MDPV) may adversely affect neural integrity in the
      developing CNS. 

PMID- 25063210
TI  - Breast volume estimation from systematic series of CT scans using the Cavalieri
      principle and 3D reconstruction.
AB  - OBJECTIVES: Preoperative breast volume estimation is very important for the
      success of the breast surgery. In the present study, two different breast volume
      determination methods, Cavalieri principle and 3D reconstruction were compared.
      MATERIAL AND METHODS: Consecutive sections were taken in slice thickness of 5 mm.
      Every 2nd breast section in a set of consecutive sections was selected. We marked
      breast tissue with blue line on each selected section, and so prepared CT scans
      used for breast volume estimation. The volumes of the 60 breasts were estimated
      using the Cavalieri principle and 3D reconstruction. RESULTS: The mean breast
      volume value was established to be 467.79 +/- 188.90 cm(3) with Cavalieri method
      and 465.91 +/- 191.41 cm(3) with 3D reconstruction. The mean CE for the estimates
      in this study was calculated as 0.25%. Skin-sparing volume was about 91.64% of
      the whole breast volume. Both methods are very accurate and have a strong linear
      association. CONCLUSION: Our results suggest that the calculation of breast
      volume or its part in vivo from systematic series of CT scans using the Cavalieri
      principle or 3D breast reconstruction is accurate enough to have a significant
      clinical benefit in planning reconstructive breast surgery. These methods can
      help the surgeon guide the choice of the most appropriate implant or/and flap
      preoperatively.

PMID- 25063211
TI  - Ultra low-dose chest CT using filtered back projection: comparison of 80-, 100-
      and 120 kVp protocols in a prospective randomized study.
AB  - PURPOSE: To assess lesion detection and diagnostic image quality of filtered back
      projection (FBP) reconstruction technique in ultra low-dose chest CT
      examinations. METHODS AND MATERIALS: In this IRB-approved ongoing prospective
      clinical study, 116 CT-image-series at four different radiation-doses were
      performed for 29 patients (age, 57-87 years; F:M - 15:12; BMI 16-32 kg/m(2)). All
      patients provided written-informed-consent for the acquisitions of additional
      ultra low-dose (ULD) series on a 256-slice MDCT (iCT, Philips Healthcare). In
      addition to their clinical standard-dose chest CT (SD, 120 kV mean CTDIvol, 6 +/-
      1 mGy), ULD-CT was subsequently performed at three-dose-levels (0.9 mGy [120 kV];
      0.5 mGy [100 kV] and 0.2 mGy [80 kV]). Images were reconstructed with FBP (2.5mm
      1.25 mm) resulting into four-stacks: SD-FBP (reference-standard), FBP0.9, FBP0.5,
      and FBP0.2. Four thoracic-radiologists from two-teaching-hospitals independently
      evaluated data for lesion-detection and visibility-of-small-structures.
      Friedman's-non-parametric-test with post hoc Dunn's-test was used for data
      analysis. RESULTS: Interobserver-agreement was substantial between radiologists
      (k=0.6-0.8). With pooled analysis, 146-pulmonary (27-groundglass-opacities, 64
      solid-lung-nodules, 7-consolidations, 27-emphysema) and 347-mediastinal/soft
      tissue lesions (87-mediastinal, 46-hilar, 62-axillary-lymph-nodes, and 11
      mediastinal-masses) were evaluated. Compared to the SD-FBP, 100% pulmonary
      lesions were seen with FBP0.9, up to 81% with FBP0.5 (missed: 4), and up to 30%
      with FBP0.2 images (missed:16). Compared to SD-FBP, all enlarged mediastinal
      lymph-nodes were seen with FBP0.9 images. All mediastinal-masses (>2 cm, 11/11)
      were seen equivalent to SD-FBP images at 0.9 mGy. Across all sizes of patients,
      FBP0.9 images had optimal visualization for lung findings. They were optimal for
      mediastinal soft tissues for only non-obese patients. CONCLUSION: Filtered-back
      projection technique allows optimal lesion detection and acceptable image quality
      for chest-CT examinations at CDTIvol of 0.9 mGy for lung and mediastinal findings
      in selected sizes of patients.

PMID- 25063212
TI  - Risk factor analysis of pulmonary hemorrhage complicating CT-guided lung biopsy
      in coaxial and non-coaxial core biopsy techniques in 650 patients.
AB  - PURPOSE: To evaluate the risk factors involved in the development of pulmonary
      hemorrhage complicating CT-guided biopsy of pulmonary lesions in coaxial and non
      coaxial techniques. MATERIALS AND METHODS: Retrospective study included CT-guided
      percutaneous lung biopsies in 650 consecutive patients (407 males, 243 females;
      mean age 54.6 years, SD: 5.2) from November 2008 to June 2013. Patients were
      classified according to lung biopsy technique in coaxial group (318 lesions) and
      non-coaxial group (332 lesions). Exclusion criteria for biopsy were: lesions <5mm
      in diameter, uncorrectable coagulopathy, positive-pressure ventilation, severe
      respiratory compromise, pulmonary arterial hypertension or refusal of the
      procedure. Risk factors for pulmonary hemorrhage complicating lung biopsy were
      classified into: (a) patient's related risk factors, (b) lesion's related risk
      factors and (d) technical risk factors. Radiological assessments were performed
      by two radiologists in consensus. Mann-Whitney U test and Fisher's exact tests
      for statistical analysis. p values <0.05 were considered statistically
      significant. RESULTS: Incidence of pulmonary hemorrhage was 19.6% (65/332) in non
      coaxial group and 22.3% (71/318) in coaxial group. The difference in incidence
      between both groups was statistically insignificant (p=0.27). Hemoptysis
      developed in 5.4% (18/332) and in 6.3% (20/318) in the non-coaxial and coaxial
      groups respectively. Traversing pulmonary vessels in the needle biopsy track was
      a significant risk factor of the development pulmonary hemorrhage (incidence:
      55.4% (36/65, p=0.0003) in the non-coaxial group and 57.7% (41/71, p=0.0013) in
      coaxial group). Other significant risk factors included: lesions of less than 2
      cm (p value of 0.01 and 0.02 in non-coaxial and coaxial groups respectively),
      basal and middle zonal lesions in comparison to upper zonal lung lesions (p=0.002
      and 0.03 in non-coaxial and coaxial groups respectively), increased lesion's
      depth from the pleural surface (p=0.021 and 0.018 in non-coaxial and coaxial
      groups respectively), increased distance of traversed lung in the needle track of
      more than 2.5 cm (p=0.001 in both groups). Insignificant risk factors were
      patient's age, gender or emphysema in both groups (p value >0.1 in both groups).
      Concomitant incidence of pneumothorax was 32.3% (21/65) in non-coaxial group and
      36.6% (26/71) in coaxial group. Pulmonary hemorrhage in the majority of cases was
      treated conservatively. CONCLUSION: Pulmonary hemorrhage complicating CT-guided
      core biopsy of pulmonary lesions, showed insignificant difference between coaxial
      and non-coaxial techniques. Significant risk factors of pulmonary hemorrhage
      included small and basal lesions, increased lesion's depth from pleural surface,
      increased length of aerated lung parenchyma crossed by biopsy needle and passing
      through vessels within the lung during puncture.

PMID- 25063213
TI  - (123)I-mIBG scintigraphy: yet another risk stratifier for the heart failure
      toolbox!

PMID- 25063214
TI  - Utility of reprojected tomograms.

PMID- 25063215
TI  - SPECT myocardial perfusion images of an undiagnosed idiopathic true left
      ventricular aneurysm.

PMID- 25063216
TI  - Hydrophilization and hydrophobic recovery in polymers obtained by casting of
      polymer solutions on water surface.
AB  - We demonstrate the possibility of hydrophilization of polymer films in situ under
      the process of their preparation. The polymer surface is hydrophilized when the
      polymer solution is spread on the water surface and the solvent is evaporated.
      Essential hydrophilization of the polymer surface is achieved under this process.
      We relate the observed hydrophilization of polymer films to the dipole-dipole
      interaction of the polar moieties of polymer chains with highly polar water
      molecules. The dipole-dipole interaction between water molecules and polar groups
      of polymer chains, orienting the polar groups of a polymer, may prevail over the
      London dispersion forces. The process, reported in the paper, allows to
      manufacture the films in which the hydrophilic moieties of the polymer molecule
      are oriented toward the polymer/air interface. It is demonstrated that even such
      traditionally extremely hydrophobic polymers as polydimethylsiloxane can be
      markedly hydrophilized. This hydrophilization, however, does not persist forever.
      After removal from the water surface, hydrophobic recovery was observed, i.e.
      polymer films restored their hydrophobicity with time. The characteristic time of
      the hydrophobic recovery is on the order of magnitude of hours. 

PMID- 25063217
TI  - Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling
      and pulmonary hypertension by promoting phenotypic modulation of small pulmonary
      arteries.
AB  - Phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) plays an
      important role during hypoxia-induced vascular remodeling and pulmonary
      hypertension (PAH). We had previously shown that calcium-sensing receptor (CaSR)
      is expressed in rat PASMCs. However, little is known about the role of CaSR in
      phenotypic modulation of PASMCs in hypoxia-induced PAH as well as the underlying
      mechanisms. In this study, we investigated whether CaSR induces the proliferation
      of PASMCs in small pulmonary arteries from both rats and human with PAH. PAH was
      induced by exposing rats to hypoxia for 7-21 days. The mean pulmonary arterial
      pressure (mPAP), right ventricular hypertrophy index (RVI), the percentage of
      medial wall thickness to the external diameter (WT %), and cross-sectional total
      vessel wall area to the total area (WA %) of small pulmonary arteries were
      determined by hematoxylin and eosin (HE), masson trichrome and Weigert's
      staining. The protein expressions of matrix metalloproteinase (MMP)-2 and MMP-9,
      the tissue inhibitors of metalloproteinase (TIMP)-3, CaSR, proliferating cell
      nuclear antigen (PCNA), phosphorylated extracellular signal-regulated kinase (p
      ERK), and smooth muscle cell (SMC) phenotype marker proteins in rat small
      pulmonary arteries, including calponin, SMalpha-actin (SMAalpha), and osteopontin
      (OPN), were analyzed by immunohistochemistry and Western blotting, respectively.
      In addition, immunohistochemistry was applied to paraffin-embedded human tissues
      from lungs of normal human and PAH patients with chronic heart failure (PAH/CHF).
      Compared with the control group, mPAP, RVI, WT % and WA % in PAH rats were
      gradually increased with the prolonged hypoxia. At the same time, the expressions
      of CaSR, MMP-2, MMP-9, TIMP-3, PCNA, OPN, and p-ERK were markedly increased,
      while the expressions of SMAalpha and calponin were significantly reduced in lung
      tissues or small pulmonary arteries of PAH rats. Neomycin (an agonist of CaSR)
      enhanced but NPS2390 (an antagonist of CaSR) weakened these hypoxic effects. We
      further found that the expression change of CaSR, PCNA, and SMC phenotypic marker
      proteins in PAH/CHF lungs was similar to those in PAH rats. Our data suggest that
      CaSR is involved in the pulmonary vascular remodeling and PAH by promoting
      phenotypic modulation of small pulmonary arteries.

PMID- 25063218
TI  - The effect of resveratrol and its methylthio-derivatives on EGFR and Stat3
      activation in human HaCaT and A431 cells.
AB  - Epidermal growth factor receptor (EGFR) interacting with Stat3 is considered to
      be an attractive therapeutic target. In the current study, we investigated the
      effect of resveratrol and its two 4'-methylthio-trans-stilbene derivatives (3-M
      4'-MTS; S2) (3,5-DM-4"-MTS; S5) on EGFR and Stat3 activation in human
      immortalized HaCaT keratinocytes and epidermoid carcinoma A431 cells. In the
      HaCaT cells both derivatives, similarly as resveratrol, decreased the total level
      of the EGFR receptor. In the A431 cells, resveratrol in the higher dose
      significantly (p < 0.05) reduced Y1173 and Y1068 EGFR residue phosphorylation,
      while S2 affected only the phosphorylation of the Y1068 residue. In this cell
      line, resveratrol in both tested doses and the S2 derivative in the lower
      concentration significantly diminished Stat3 binding capacity to the DNA
      consensus site. The effect of the tested compounds on Stat3 activation in HaCaT
      cells was only slightly affected. These results indicate that methylthiostilbenes
      are not more potent modulators of the EGFR/Stat3 complex than resveratrol and
      that introducing an additional methoxy group makes them less effective.

PMID- 25063219
TI  - MiRNA-26b inhibits the proliferation, migration, and epithelial-mesenchymal
      transition of lens epithelial cells.
AB  - MicroRNAs (miRNAs) are a class of small endogenous gene regulators that play
      important roles in various developmental and pathological processes. However,
      little is known about the precise identity and functions of miR-26b in posterior
      capsule opacification (PCO). In this study, we report that the expression of miR
      26b is decreased in human PCO-attached lens epithelial cells (LECs) and SRA01/04
      cells in the presence of TGF-beta2. Overexpression of miR-26b inhibited the
      proliferation of LECs based on MTT assays and BrdU incorporation assays. In
      addition, the overexpression of miR-26b inhibited the migration ability of LECs,
      as shown by wound-healing and transwell migration assays. The overexpression of
      miR-26b increased the level of the lens epithelial marker E-cadherin and reduced
      the levels of mesenchymal-related proteins, such as fibronectin, a-SMA, and type
      I collagen, in SRA01/04 cells in the presence of TGF-beta2. Furthermore, the
      upregulation of E-cadherin and downregulation of mesenchymal-related proteins
      were induced in human PCO-attached LECs transfected with miR-26b mimics. We
      further demonstrated that Smad4 and COX-2 are targets of miR-26b in LECs using
      luciferase reporter assays. These data reveal that miR-26b can inhibit the
      proliferation, migration, and EMT of lens epithelial cells, and restoration of
      miRNA-26b may be a potential, novel therapeutic target for the prevention and
      treatment of posterior capsule opacification.

PMID- 25063220
TI  - Role of reactive oxygen species in angiotensin II: induced receptor activator of
      nuclear factor-kappaB ligand expression in mouse osteoblastic cells.
AB  - Angiotensin II (Ang II) has been shown to induce receptor activator of nuclear
      factor-kappaB ligand (RANKL) expression in osteoblasts associated with its effect
      on reactive oxygen species (ROS) production. The objective of the present study
      was to investigate the potential pathways by which Ang II induces RANKL
      expression and the role of ROS in Ang II-induced RANKL expression in mouse
      osteoblastic MC3T3-E1 cells. Treatment with Ang IIinduced RANKL expression in a
      dose- and time-dependent manner in osteoblasts, which was attenuated by pre
      treatment with an AT1 receptor antagonist (olmesartan), ROS scavenger (N
      acetylcysteine, NAC), or the ERK inhibitor (U0126), but not with AT2R antagonist
      (PD123319). Furthermore, Ang II enhanced AT1R and NAD(P)H oxidase (NOX) p22(phox)
      and p67(phox) expression and activity in osteoblasts. In addition, Ang II
      promoted ROS production, which was mitigated by pre-treatment with olmesartan or
      a NOX inhibitor (diphenyleneiodonium, DPI), but not with PD1123319 or U0126, in
      osteoblasts. Moreover, Ang II enhanced the ERK1/2 phosphorylation, which was
      abrogated by pre-treatment with olmesartan, NAC, DPI, or U0126 in osteoblasts.
      These results suggest that Ang II, through its AT1R, enhanced NOX activity and
      ROS production, and activated the ERK pathway to up-regulate RANKL expression in
      osteoblasts in vitro.

PMID- 25063222
TI  - Management of heterotopic ossification and restricted forearm rotation after
      tension band wiring for olecranon fracture.
AB  - A 32-year-old lady presented to our clinic with persistent painful restriction of
      her dominant forearm movements for three months after tension band wiring of
      olecranon. She had full elbow flexion and extension; however, her forearm
      rotations were restricted and painful. Investigations revealed prominent tips of
      the wire, eroding the radial tuberosity with heterotopic ossification between the
      radius and ulna. As there was no synostosis, the patient had implant exit. During
      surgery, before implant removal, examination under anaesthesia revealed a
      mechanical block of the rotation beyond 30 degrees  on pronation and supination
      from neutral. However, after the removal of implant, the mechanical block eased
      off and with gentle manipulation, full pronation and supination were achieved. At
      the final follow-up at 6 months, the patient had full pain-free forearm rotation
      with regression of heterotopic ossification. Our case report highlights the
      importance of intra-operative assessment of wire tips at full supination and
      pronation, and in patients with restricted forearm rotation, CT scan may be
      needed to assess the position of the hardware is essential as it can progress to
      synostosis. In cases with prominent hardware, removal of the implant may suffice
      if performed before the development of synostosis. 

PMID- 25063221
TI  - MicroRNA 520d-3p inhibits gastric cancer cell proliferation, migration, and
      invasion by downregulating EphA2 expression.
AB  - Aberrant expression of microRNAs (miRNAs) has been shown to play important roles
      in cancer progression as a result of changes in expression of their target genes.
      In this study, we investigated the roles of miR-520d-3p on gastric cancer (GC)
      cell proliferation, migration, and invasion, and confirmed that this miRNA
      regulates EphA2 expression. The mRNA expression levels of miR-520d-3p and EphA2
      in GC tissues and cell lines were evaluated. The clinical and prognostic
      significance of miR-520d-3p was assessed. The biological function of miR-520d-3p
      in GC cells was investigated using a methylthiazolyldiphenyl-tetrazolium bromide
      assay, cell cycle assay, transwell invasion assay, and wound-healing assay. miR
      520d-3p expression was down-regulated and inversely correlated with the
      expression of EphA2 in GC tissues and cell lines. Lower expression of miR-520d-3p
      was associated with tumor invasion (P = 0.0357), lymph nodes metastasis (P =
      0.0272), a higher clinical stage (P = 0.0041), and poorer overall survival (P =
      0.0105). Luciferase assays revealed that miR-520d-3p inhibited EphA2 expression
      by targeting the 3'-untranslated region of EphA2 mRNA. Overexpression of miR-520d
      3p dramatically inhibited the proliferation, cell cycle progression, invasion,
      and migration of GC cells, while down-regulation substantially promoted these
      properties. Moreover, c-Myc, CyclinD1, and matrix metalloproteinase-9 expression
      levels were down-regulated in miR-520d-3p mimic-transfected cells and up
      regulated in miR-520d-3p inhibitor-transfected cells. Taken together, our data
      showed that miR-520d-3p appears to contribute to GC progression via the
      regulation of EphA2 and could serve as a novel prognostic and potential
      therapeutic marker.

PMID- 25063223
TI  - Expression of selectins and P-selectin glycoprotein ligand-1 in dogs with
      lymphocytic-plasmacytic enteritis.
AB  - Lymphocytic-plasmacytic enteritis (LPE) is the most common form of inflammatory
      bowel disease (IBD) affecting the canine small intestine; however, the molecular
      pathogenesis of this disease remains unclear. Although selectins and their
      ligands play a critical role as cell adhesion molecules during inflammation,
      there is very little information about their involvement in canine LPE. The aim
      of this study was to evaluate transcript expression of selectins (E-, L-, and P-
      selectin) and P-selectin glycoprotein ligand-1 (PSGL-1) in the duodenal mucosa of
      21 dogs with LPE and 10 healthy laboratory beagles. Duodenal expression of E
      selectin, L-selectin, P-selectin, and PSGL-1 was quantified by real-time reverse
      transcription PCR. Correlations between clinical severity, histopathological
      grade, selectins, and PSGL-1 were analyzed by Spearman's rank test. Transcript
      expression of duodenal E- and P-selectins and PSGL-1 was higher in dogs with LPE
      than in healthy laboratory beagles; however, there was no difference in L
      selectin expression. Positive correlations between E- and L-selectin and between
      L- and P-selectin were observed in the duodenum of LPE dogs. The selectins and
      ligand may recruit circulating inflammatory cells into the lesion. These findings
      improve our understanding of the inflammatory cascade of canine LPE.

PMID- 25063224
TI  - Impact of a probiotic Bacillus cereus strain on the jejunal epithelial barrier
      and on the NKG2D expressing immune cells during the weaning phase of piglets.
AB  - In a feeding experiment, the probiotic Bacillus cereus var. Toyoi was fed to sows
      and piglets in order to test whether it influences the stress response of
      enterocytes, thereby causing intestinal immune activation, possibly accompanied
      by an impairment of the epithelial integrity. The impact of B. cereus on the
      piglets' intestinal enterocytes (EC) and on the communicating intraepithelial
      lymphocytes (IEL) was investigated during the weaning phase where significant
      immunological changes might be expected. The expression of the stress-induced MHC
      class I-related molecule 2 (MIC2) and the UL16 binding protein (ULBP) was
      measured in jejunal EC and the frequencies of the main present IEL populations in
      the jejunum were monitored. To find out which of the IEL populations can be
      activated by the stress-induced molecules the sorted IEL were tested for the
      expression of the activating natural killer receptor 2D (NKG2D). The piglets fed
      with B. cereus showed an impaired intestinal barrier function shortly after
      weaning. However, a significant impact on the expression of stress-induced
      molecules was not observed. The mRNA expression of NKG2D was confirmed in
      intraepithelial CD5+ gammadelta T cells. The ratio of IEL (CD45+) to EC was lower
      in the B. cereus treated group, which could be explained by lower frequencies of
      CD8alphabeta+ T cells in the jejunal epithelium (p <= 0.005 for ages 32 and 34).
      Although a consistently increased expression of stress-induced MHC class I
      related molecules was not found, this study suggests a negative impact of B.
      cereus on the intestinal barrier function and supports immune-modulating
      properties of the probiotic feed supplement.

PMID- 25063225
TI  - A cDNA microarray analysis to identify genes involved in the acute-phase response
      pathway of the olive flounder after infection with Edwardsiella tarda.
AB  - The acute-phase response (APR) is an important systemic reaction that occurs
      within hours of an inflammatory signal caused by physical bodily injury or
      microbial infection. To investigate the APR of the olive flounder (Paralichthys
      olivaceus) following infection with a pathogen, we established an expressed
      sequence tag (EST)-based cDNA microarray chip composed of 13,061 PCR-amplified
      cDNAs encoding unique genes selected from an olive flounder EST analysis.
      Microarray analyses showed that the set of genes involved in the APR was strongly
      up-regulated in the liver of the olive flounder after infection with Edwardsiella
      tarda. Among the up-regulated genes, catechol-O-methyltransferase domain
      containing protein 1, six-transmembrane prostate protein, haptoglobin precursor,
      and toll-like receptor 5 soluble form were particularly strongly up-regulated.
      Interestingly, the toll-like receptor 5 soluble form, which has not yet been
      detected in mammals, was up-regulated as much as 250-fold upon E. tarda
      infection. These results suggest that the APR mechanism of fish may be regulated
      differently from that of mammals. The data described here contribute toward our
      collective understanding of APR, especially in fish. 

PMID- 25063226
TI  - Taxanes as a risk factor for acute adverse reactions to iodinated contrast media
      in cancer patients.
AB  - BACKGROUND: The impact of cytotoxic agents on the risk of acute allergy-like
      adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections
      is unknown. METHODS: We retrospectively reviewed 13,565 computed tomography (CT)
      scans performed in a consecutive cohort of cancer patients from January 1, 2010
      to December 31, 2012. Episodes of acute ICM-related ARs were reported to the
      pharmacovigilance officer. The following matched comparisons were made: tax code,
      gender, primary tumor, antineoplastic therapy, and date of last cycle.
      Concomitant antineoplastic treatment was classified into five groups: platinum,
      taxane, platinum plus taxane, other, and no treatment group (no therapy had been
      administered in the previous 24 months). Logistic regression was used to estimate
      odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute
      ICM-related ARs. RESULTS: Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95%
      CI: 0.74-1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe,
      including one fatality. The overall incidence was significantly higher in
      patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane
      groups (p = .007), whereas no correlation was found with gender, number of
      previous CT scans, site of disease, or treatment setting. Multivariate analysis
      confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14
      2.63) and for the taxane group (in comparison with the no treatment group; OR:
      2.06; 95% CI: 1.02-4.16). CONCLUSION: Among cancer patients, concomitant
      treatment with taxanes and younger age would seem to be risk factors for ICM
      related ARs.

PMID- 25063227
TI  - European perspective on multiple myeloma treatment strategies in 2014.
AB  - The treatment of multiple myeloma has undergone significant changes and has
      resulted in the achievement of molecular remissions, the prolongation of
      remission duration, and extended survival becoming realistic goals, with a cure
      being possible in a small but growing number of patients. In addition, nowadays
      it is possible to categorize patients more precisely into different risk groups,
      thus allowing the evaluation of therapies in different settings and enabling a
      better comparison of results across trials. Here, we review the evidence from
      clinical studies, which forms the basis for our recommendations for the
      management of patients with myeloma. Treatment approaches depend on "fitness,"
      with chronological age still being an important discriminator for selecting
      therapy. In younger, fit patients, a short three drug-based induction treatment
      followed by autologous stem cell transplantation (ASCT) remains the preferred
      option. Consolidation and maintenance therapy are attractive strategies not yet
      approved by the European Medicines Agency, and a decision regarding post-ASCT
      therapy should only be made after detailed discussion of the pros and cons with
      the individual patient. Two- and three-drug combinations are recommended for
      patients not eligible for transplantation. Treatment should be administered for
      at least nine cycles, although different durations of initial therapy have only
      rarely been compared so far. Comorbidity and frailty should be thoroughly
      assessed in elderly patients, and treatment must be adapted to individual needs,
      carefully selecting appropriate drugs and doses. A substantial number of new
      drugs and novel drug classes in early clinical development have shown promising
      activity. Their introduction into clinical practice will most likely further
      improve treatment results. 

PMID- 25063228
TI  - Mild primary hyperparathyroidism: a literature review.
AB  - The biochemical profile of classic primary hyperparathyroidism (pHPT) consists of
      both elevated calcium and parathyroid hormone levels. The standard of care is
      parathyroidectomy unless prohibited by medical comorbidities. Because more
      patients are undergoing routine bone density evaluation and neck imaging studies
      for other purposes, there is a subset of people identified with a biochemically
      mild form of the pHPT that expresses itself as either elevated calcium or
      parathyroid hormone levels. These patients often do not fall into the criteria
      for operation based on the National Institutes of Health consensus guidelines,
      and they can present a challenge of diagnosis and management. The purpose of this
      paper is to review the available literature on mild pHPT in an effort to better
      characterize this patient population and to determine whether patients benefit
      from parathyroidectomy. Evidence suggests that there are patients with mild pHPT
      who have overt symptoms that are found to improve after parathyroidectomy. There
      is also a group of patients with biochemically mild pHPT who are found to
      progress to classic pHPT over time; however, it is not predictable which group of
      patients this will be. Early intervention for this group with mild pHPT may
      prevent progression of bone, psychiatric, and renal complications, and
      parathyroidectomy has proven safe in appropriately selected patients at high
      volume centers. 

PMID- 25063229
TI  - Differential risk factors for HIV drug and sex risk-taking among non-treatment
      seeking hospitalized injection drug users.
AB  - Injection drug users (IDUs) are at increased risk of contracting HIV. From a
      clinical trial assessing an intervention to enhance the linkage of hospitalized
      patients to opioid treatment after discharge, we conducted multivariate analysis
      of baseline data from hospitalized IDUs with a history of opioid dependence (n =
      104) to identify differences in factors predicting HIV drug and sex risk
      behaviors. Factors significantly associated with HIV drug risk were being non
      Hispanic Caucasian and recent cocaine use. Being female, binge drinking, and
      poorer mental health were significantly associated with higher sex risk. Because
      factors predicting HIV sex risk behaviors differ from those predicting HIV drug
      risk, interventions aimed at specific HIV risks should have different behavioral
      and substance use targets.

PMID- 25063230
TI  - Donor-Acceptor Conjugated Linear Polyenes: A Study of Excited State
      Intramolecular Charge Transfer, Photoisomerization and Fluorescence Probe
      Properties.
AB  - Numerous studies of donor-acceptor conjugated linear polyenes have been carried
      out with the goal to understand the exact nature of the excited state electronic
      structure and dynamics. In this article we discuss our endeavours with regard to
      the excited state intramolecular charge transfer, photoisomerization and
      fluorescence probe properties of various donor-acceptor substituted compounds of
      diphenylpolyene [Ar(CH = CH) n Ar] series and ethenylindoles.

PMID- 25063231
TI  - Absence of substance P and the sympathetic nervous system impact on bone
      structure and chondrocyte differentiation in an adult model of endochondral
      ossification.
AB  - OBJECTIVE: Sensory and sympathetic nerve fibers (SNF) innervate bone and
      epiphyseal growth plate. The role of neuronal signals for proper endochondral
      ossification during skeletal growth is mostly unknown. Here, we investigated the
      impact of the absence of sensory neurotransmitter substance P (SP) and the
      removal of SNF on callus differentiation, a model for endochondral ossification
      in adult animals, and on bone formation. METHODS: In order to generate callus,
      tibia fractures were set in the left hind leg of wild type (WT), tachykinin 1
      deficient (Tac1-/-) mice (no SP) and animals without SNF. Locomotion was tested
      in healthy animals and touch sensibility was determined early after fracture.
      Callus tissue was prepared for immunofluorescence staining for SP, neurokinin1
      receptor (NK1R), tyrosine-hydroxylase (TH) and adrenergic receptors alpha1,
      alpha2 and beta2. At the fracture site, osteoclasts were stained for TRAP,
      osteoblasts were stained for RUNX2, and histomorphometric analysis of callus
      tissue composition was performed. Primary murine bone marrow derived macrophages
      (BMM), osteoclasts, and osteoblasts were tested for differentiation, activity,
      proliferation and apoptosis in vitro. Femoral fractures were set in the left hind
      leg of all the three groups for mechanical testing and MUCT-analysis. RESULTS:
      Callus cells stained positive for SP, NK1R, alpha1d- and alpha2b adrenoceptors
      and remained beta2-adrenoceptor and TH-negative. Absence of SP and SNF did not
      change the general locomotion but reduces touch sensitivity after fracture. In
      mice without SNF, we detected more mesenchymal callus tissue and less
      cartilaginous tissue 5 days after fracture. At day 13 past fracture, we observed
      a decrease of the area covered by hypertrophic chondrocytes in Tac1-/- mice and
      mice without SNF, a lower number of osteoblasts in Tac1-/- mice and an increase
      of osteoclasts in mineralized callus tissue in mice without SNF. Apoptosis rate
      and activity of osteoclasts and osteoblasts isolated from Tac1-/- and
      sympathectomized mice were partly altered in vitro. Mechanical testing of
      fractured- and contralateral legs 21 days after fracture, revealed an overall
      reduced mechanical bone quality in Tac1-/- mice and mice without SNF. MUCT
      analysis revealed clear structural alteration in contralateral and fractured legs
      proximal of the fracture site with respect to trabecular parameters, bone mass
      and connectivity density. Notably, structural parameters are altered in fractured
      legs when related to unfractured legs in WT but not in mice without SP and SNF.
      CONCLUSION: The absence of SP and SNF reduces pain sensitivity and mechanical
      stability of the bone in general. The micro-architecture of the bone is
      profoundly impaired in the absence of intact SNF with a less drastic effect in SP
      deficient mice. Both sympathetic and sensory neurotransmitters are indispensable
      for proper callus differentiation. Importantly, the absence of SP reduces bone
      formation rate whereas the absence of SNF induces bone resorption rate. Notably,
      fracture chondrocytes produce SP and its receptor NK1 and are positive for alpha
      adrenoceptors indicating an endogenous callus signaling loop. We propose that
      sensory and sympathetic neurotransmitters have crucial trophic effects which are
      essential for proper bone formation in addition to their classical neurological
      actions.

PMID- 25063232
TI  - Exercise alters liver mitochondria phospholipidomic profile and mitochondrial
      activity in non-alcoholic steatohepatitis.
AB  - Mitochondrial membrane lipid composition is a critical factor in non-alcoholic
      steatohepatitis (NASH). Exercise is the most prescribed therapeutic strategy
      against NASH and a potential modulator of lipid membrane. Thus, we aimed to
      analyze whether physical exercise exerted preventive (voluntary physical activity
      - VPA) and therapeutic (endurance training - ET) effect on NASH-induced
      mitochondrial membrane changes. Sprague-Dawley rats (n=36) were divided into
      standard-diet sedentary (SS, n=12), standard-diet VPA (SVPA, n=6), high-fat diet
      sedentary (HS, n=12) and high-fat diet VPA (HVPA, n=6). After 9 weeks of diet
      specific feeding, half of SS and HS group were engaged in an ET program for 8
      weeks/5 day/week/1h/day (SET, HET). Liver mitochondria were isolated for oxygen
      consumption and transmembrane-electric potential (DeltaPsi) assays. Mitochondrial
      phospholipid classes and fatty acids were quantified through thin layer
      chromatography and gas chromatography, respectively, while cardiolipin (CL),
      phosphatidylcholine (PC) phosphatidylethanolamine (PE) and phosphatidylinositol
      (PI) molecular profile was determined by electrospray mass spectrometry. In
      parallel with histological signs of NASH, high-fat diet decreased PI, CL and
      PC/PE ratio, whereas PE and phosphatidic acid content increased in sedentary
      animals (HS vs. SS). Moreover, a decrease in linolelaidic, monounsaturated fatty
      acids content and an increase in saturated fatty acids (SFAS) were observed.
      Along with phospholipidomic alterations, HS animals showed a decrease in
      respiratory control ratio (RCR), DeltaPsi and FCCP-induced uncoupling respiration
      (HS vs. SS). Both phospholipidomic (PC/PE, SFAS) and mitochondrial respiratory
      alterations were counteracted by exercise interventions. Exercise used as
      preventive (VPA) or therapeutic (ET) strategies preserved liver mitochondrial
      phospholipidomic profile and maintained mitochondrial function in a model of
      NASH. 

PMID- 25063233
TI  - Functional overlap and divergence between ALS and bvFTD.
AB  - Amyotrophic lateral sclerosis (ALS) and behavioral variant frontotemporal
      dementia (bvFTD) lie on a clinical, pathologic, and genetic continuum.
      Neuroimaging techniques have proven to be potentially useful to unravel the
      shared features of these syndromes. Using resting-state functional magnetic
      resonance imaging (RS-fMRI), we investigated functional connectivity of brain
      networks in 15 ALS and 15 bvFTD patients in early stages of disease and 15
      healthy controls, looking expressly for connectivity pattern divergence or
      overlap between the 2 disorders. Compared with controls, we found decreased RS
      fMRI signals within sensorimotor, right frontoparietal, salience, and executive
      networks in both patient groups. Within the default mode network (DMN), divergent
      connectivity patterns were observed, with RS-fMRI signals in the posterior
      cingulate cortex enhanced in bvFTD patients and suppressed in ALS patients. Our
      findings confirm that ALS and bvFTD not only broadly share common RS-fMRI
      connectivity patterns, probably representing different phenotypical expressions
      of the same neurodegenerative process, but also differ in the DMN, probably
      reflecting a different stage of neurodegeneration. 

PMID- 25063235
TI  - Health-income inequality: the effects of the Icelandic economic collapse.
AB  - INTRODUCTION: Health-income inequality has been the focus of many studies. The
      relationship between economic conditions and health has also been widely studied.
      However, not much is known about how changes in aggregate economic conditions
      relate to health-income inequality. Nevertheless, such knowledge would have both
      scientific and practical value as substantial public expenditures are used to
      decrease such inequalities and opportunities to do so may differ over the
      business cycle. For this reason we examine the effect of the Icelandic economic
      collapse in 2008 on health-income inequality. METHODS: The data used come from a
      health and lifestyle survey carried out by the Public Health Institute of Iceland
      in 2007 and 2009. A stratified random sample of 9,807 individuals 18-79 years old
      received questionnaires and a total of 42.1% answered in both years. As measures
      of health-income inequality, health-income concentration indices are calculated
      and decomposed into individual-level determinants. Self-assessed health is used
      as the health measure in the analyses, but three different measures of income are
      used: individual income, household income, and equivalized household income.
      RESULTS: In both years there is evidence of health-income inequality favoring the
      better off. However, changes are apparent between years. For males health-income
      inequality increases after the crisis while it remains fairly stable for females
      or slightly decreases. The decomposition analyses show that income itself and
      disability constitute the most substantial determinants of inequality. The
      largest increases in contributions between years for males come from being a
      student, having low education and being obese, as well as age and income but
      those changes are sensitive to the income measure used. CONCLUSIONS: Changes in
      health and income over the business cycle can differ across socioeconomic strata,
      resulting in cyclicality of income-related health distributions. As substantial
      fiscal expenditures go to limiting the relationship between income and health,
      the business-cycle effect on equality, which has up until now not received much
      attention, needs to be considered.

PMID- 25063236
TI  - Uncommon pancreatic tumors and pseudotumors.
AB  - A heterogeneous group of uncommon neoplastic and non-neoplastic pancreatic
      pathologies exists that can mimic pancreatic adenocarcinoma. These "imitators"
      are unique and may demonstrate characteristic clinical and imaging features.
      Imaging characteristics of some of these diverse lesions are not well described
      in the literature, and erroneous diagnoses of these entities as pancreatic
      carcinoma may be responsible for unnecessary surgeries. Knowledge of these
      selected pancreatic pathologies is essential to facilitate optimal patient
      management. 

PMID- 25063234
TI  - Dissecting histone deacetylase role in pulmonary arterial smooth muscle cell
      proliferation and migration.
AB  - Pulmonary Arterial Hypertension (PAH) is a rare and devasting condition
      characterized by elevated pulmonary vascular resistance and pulmonary artery
      pressure leading to right-heart failure and premature death. Pathologic
      alterations in proliferation, migration and survival of all cell types composing
      the vascular tissue play a key role in the occlusion of the vascular lumen. In
      the current study, we initially investigated the action of selective class I and
      class II HDAC inhibitors on the proliferation and migration of pulmonary artery
      smooth muscle cells (PASMCs) after exposure to Platelet Derived Growth Factor
      (PDGF). Class I HDAC inhibitors were able to counteract the hyperproliferative
      response to PDGF, reducing both proliferation and migration in PASMCs, while
      class II were ineffective. Selective silencing with siRNAs targeted against
      different HDACs revealed a major role of class I, and within this class, of HDAC1
      in mediating PDGF-induced Akt Phosphorylation and Cyclin D1 (CycD1) expression.
      These results from these combinatorial approaches were further confirmed by the
      ability of a specific HDAC1 inhibitor to antagonize the PDGF action. The finding
      that HDAC1 is a major conductor of PDGF-induced patterning in PAH-PASMCs prompts
      the development of novel selective inhibitors of this member of class I HDACs as
      a potential tool to control lung vascular homeostasis in PAH. 

PMID- 25063237
TI  - Comparative study of MRI manifestations of acute and chronic Budd-Chiari
      syndrome.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is able to diagnose Budd-Chiari
      syndrome (BCS) by distinguishing differential imaging features of acute and
      chronic forms of the disease. However, the characteristic imaging differences are
      still not clear as previous data were mostly obtained from scattered small
      samples instead of large comparative study. AIM: To investigate MRI
      manifestations of acute and chronic (BCS), and to evaluate the value of MRI for
      diagnosis of acute and chronic BCS. METHODS AND RESULTS: We retrospectively
      compared MRI results of 24 patients with acute and 82 patients with chronic BCS
      using Mann-Whitney U test for ascites volume, and Fisher's exact test for
      intrahepatic venous collaterals and extra-hepatic venous collaterals. In the
      acute group, MRI findings suggested thrombosis in hepatic vein (HV) in all acute
      patients and additional inferior vena cava (IVC) thrombosis in 5 patients. In the
      chronic BCS group, 6 and 15 patients showed solitary obstruction either in the
      IVC or HV, respectively, while 61 patients showed combined IVC and HV
      obstruction. More patients with acute BCS presented with ascites accompanied with
      high signals on T2WI from intravenous obstructive lesions. Further, the average
      maximal spleen diameter in patients with acute BCS, and the ratio of patients
      with acute BCS developing intrahepatic venous collaterals and extra-hepatic
      venous collaterals were also lower compared with chronic BCS. All these
      differences were statistically significant. CONCLUSION: MRI indicates direct and
      indirect features of BCS, and therefore enables accurate diagnosis of acute and
      chronic BCS.

PMID- 25063238
TI  - The gallbladder: uncommon gallbladder conditions and unusual presentations of the
      common gallbladder pathological processes.
AB  - This article reviews a spectrum of gallbladder conditions that are either
      uncommon or represent unusual manifestations of common diseases. These conditions
      are divided into four major categories: (a) congenital anomalies and normal
      variants including duplication, ectopia, and lymphangioma; (b) inflammatory
      processes and stone-related diseases and complications including adenomyomatosis,
      emphysematous cholecystitis, xanthogranulomatous cholecystitis, gangrenous and
      hemorrhagic cholecystitis, perforation, gallstone ileus, and Bouveret and Mirizzi
      syndromes; (c) gallbladder neoplasms including adenocarcinoma with associated
      porcelain gallbladder, squamous cell carcinoma, lymphoma, melanoma, and
      neurofibroma. A thorough understanding of the imaging characteristics of each
      condition can help the radiologist to make a timely and accurate diagnosis, thus
      avoiding potentially harmful delays in patient management and decreasing
      morbidity and mortality rates. 

PMID- 25063240
TI  - Gas exchange and ventilation-perfusion relationships in the lung.
AB  - This review provides an overview of the relationship between
      ventilation/perfusion ratios and gas exchange in the lung, emphasising basic
      concepts and relating them to clinical scenarios. For each gas exchanging unit,
      the alveolar and effluent blood partial pressures of oxygen and carbon dioxide
      (PO2 and PCO2) are determined by the ratio of alveolar ventilation to blood flow
      (V'A/Q') for each unit. Shunt and low V'A/Q' regions are two examples of V'A/Q'
      mismatch and are the most frequent causes of hypoxaemia. Diffusion limitation,
      hypoventilation and low inspired PO2 cause hypoxaemia, even in the absence of
      V'A/Q' mismatch. In contrast to other causes, hypoxaemia due to shunt responds
      poorly to supplemental oxygen. Gas exchanging units with little or no blood flow
      (high V'A/Q' regions) result in alveolar dead space and increased wasted
      ventilation, i.e. less efficient carbon dioxide removal. Because of the
      respiratory drive to maintain a normal arterial PCO2, the most frequent result of
      wasted ventilation is increased minute ventilation and work of breathing, not
      hypercapnia. Calculations of alveolar-arterial oxygen tension difference, venous
      admixture and wasted ventilation provide quantitative estimates of the effect of
      V'A/Q' mismatch on gas exchange. The types of V'A/Q' mismatch causing impaired
      gas exchange vary characteristically with different lung diseases.

PMID- 25063239
TI  - Gender and age are associated with healthy food purchases via grocery voucher
      redemption.
AB  - INTRODUCTION: Grocery vouchers that specifically target foods associated with
      reduced cardiovascular disease (CVD) risk result in increased consumption of
      those foods. In regions with disproportionately high CVD rates, there is little
      research concerning the impact of vouchers on purchases of risk-reducing foods
      when there are no restrictions placed on grocery voucher redemption. Since many
      food assistance programs place few restrictions on type of foods that can be
      purchased, identifying demographic factors associated with purchasing habits is a
      prerequisite to promoting healthy eating. The purpose of this study was to
      determine the associations of age, gender, education and income level with
      purchasing of healthful foods through the use of a grocery voucher in a rural
      food desert (poverty rate of >=20% and >=33% of residents living >16 km from a
      large grocery store) with high rates of chronic disease. METHODS: The
      effectiveness of an intervention that included a media campaign, a $5 grocery
      voucher, local heart healthy food branding and a grocery store event was tested.
      Brief nutritional articles were published in both local newspapers during four
      consecutive weeks. These articles explained the physiological actions of healthy
      foods and listed a health-promoting recipe. During the fourth week of the media
      campaign, a voucher for a $5 grocery gift card redeemable at one of either
      community grocery stores was also printed in both local newspapers. In each
      store, foods that are known to be associated with a reduced risk of CVD were
      marked with a blue logo. Participants (N=311) completed a questionnaire that
      assessed demographics and usual servings of fruits, vegetables and grains.
      Participants received a $5 grocery card and a list of labelled foods. Returned
      grocery receipts were stapled to the questionnaires to analyse the relationship
      between demographics and food choices. RESULTS: Participants who bought at least
      one labelled food item were older (M=48.5, SD=14.7) than those who did not buy
      any of these items (M=42.3, SD=16.4; p=0.0008). There was a significant
      association between labelled food purchases and gender, with 47% of male
      participants purchasing at least one labelled food item compared with 63% of
      females in the study (p = 0.008). There were no significant associations between
      purchase of labelled food items and either education or income. The significant
      predictors were age (p=0.003) and gender (p=0.01). For every 10 year increase in
      age, there was a 29% increase in the likelihood that at least one labelled food
      item would be purchased. Male participants were 48% less likely to purchase at
      least one designated food item than female participants were. CONCLUSIONS:
      Younger adults and men may be less responsive to media-based educational
      strategies, heart-healthy food labelling and grocery vouchers to defray the cost
      of healthy eating than older adults and women. Previous studies show that
      concerns about cost and availability of foods are greater factors in the decision
      to purchase these foods than demographic characteristics. However, age and gender
      are associated with the likelihood of using grocery vouchers for the purchase of
      healthful foods. Additional research is needed to determine whether different
      educational strategies paired with food labelling and grocery vouchers may be
      successful strategies to promote purchase of healthful foods, particularly for
      men and younger adults.

PMID- 25063241
TI  - Evaluation of Xpert MTB/RIF assay performance in diagnosing extrapulmonary
      tuberculosis among adults in a tertiary care centre in India.

PMID- 25063242
TI  - Network medicine, multimorbidity and the lung in the elderly.
AB  - Noncommunicable diseases, including cardiovascular, metabolic and respiratory
      diseases, among others, are the major medical challenge of the 21st century. Most
      noncommunicable diseases are related to the ageing process and often co-occur in
      the same individual. However, it is unclear whether the index disease is somehow
      influencing the development of the other ones (comorbidity) or whether all of
      them (including the index disease) simply represent the clinical expression of
      pathological ageing (multimorbidity). The pathobiology of ageing, chronic
      obstructive pulmonary disease (COPD) and concomitant disorders is complex. A new
      field of research, known as systems biology if applied to model systems or
      network medicine if applied to human beings, has emerged over the past decade or
      so, to address biological complexity in a holistic, integrated way. It offers,
      therefore, great potential to decipher the relationship between ageing, COPD and
      comorbidities/multimorbidities. In this State of the Art review we present the
      basic concepts of systems biology, use some examples to illustrate the potential
      of network medicine to address complex medical problems, and review some recent
      publications that show how a systems-based research strategy can contribute to
      improve our understanding of multimorbidity and age-related respiratory diseases.

PMID- 25063243
TI  - The concept of control in COPD: a new proposal for optimising therapy.

PMID- 25063244
TI  - Smoking-related idiopathic interstitial pneumonia.
AB  - Cigarette smoking is a key factor in the development of numerous pulmonary
      diseases. An international group of clinicians, radiologists and pathologists
      evaluated patients with previously identified idiopathic interstitial pneumonia
      (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation
      group) identified smoking-related features in patients with a history of smoking
      (n=41). Phase 2 (validation group) determined if these features correctly
      predicted the smoking status of IIP patients (n=100) to participants blinded to
      smoking history. Finally, the investigators sought to determine if a new smoking
      related interstitial lung disease phenotype could be defined. Phase 1 suggested
      that preserved forced vital capacity with disproportionately reduced diffusing
      capacity of the lung for carbon monoxide, and various radiographic and
      histopathological findings were smoking-related features. In phase 2, the kappa
      coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists
      0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for
      smoking-related features. Eight of the 100 cases were felt to represent a
      potential smoking-related interstitial lung disease. Smoking-related features of
      interstitial lung disease were identified in a minority of smokers and were not
      specific for smoking. This study is limited by its retrospective design, the
      potential for recall bias in smoking history and lack of information on second
      hand smoke exposure. Further research is needed to understand the relationship
      between smoking and interstitial lung disease. 

PMID- 25063245
TI  - All-age relationship between arm span and height in different ethnic groups.
AB  - The objective of the present study was to establish multiethnic, all-age
      prediction equations for estimating stature from arm span in males and females.
      The arm span/height ratio (ASHR) from 13 947 subjects (40.9% females), aged 5-99
      years, from nine centres (in China, Europe, Ghana, India and Iran) was used to
      predict ASHR as a function of age using the lambda, mu and sigma method. Z-scores
      for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and
      FEV1/FVC in 1503 patients were calculated using measured height and height
      calculated from arm span and age. ASHR varied nonlinearly with age, was higher in
      males than in females and differed significantly between the nine sites. The data
      clustered into four groups: Asia, Europe, Ghana and Iran. Average predicted FEV1,
      FVC and FEV1/FVC using measured or predicted height did not differ, with standard
      deviations of 4.6% for FEV1, 5.0% for FVC and 0.3% for FEV1/FVC. The percentages
      of disparate findings for a low FEV1, FVC and FEV1/FVC in patients, calculated
      using measured or predicted height, were 4.2%, 3.2% and 0.4%, respectively; for a
      restrictive pattern, there were 1.0% disparate findings. Group- and sex-specific
      equations for estimating height from arm span and age to derive predicted values
      for spirometry are clinically useful. 

PMID- 25063246
TI  - Yield of tuberculosis contact investigations in Amsterdam: opportunities for
      improvement.
AB  - We aimed to determine the coverage and yield of tuberculosis contact
      investigation, and compliance with guidelines, and to identify opportunities for
      improvement. Data were extracted from records on contacts of pulmonary
      tuberculosis patients at the Public Health Service (Amsterdam, the Netherlands)
      from 2008 to 2011. Additional data were obtained from the national tuberculosis
      register. Among 3743 contacts of 235 pulmonary tuberculosis index patients, 2337
      (62%) were screened for latent tuberculosis infection (LTBI). Those less likely
      to be screened for LTBI included contacts of sputum smear-negative index patients
      (adjusted odds ratio (aOR) 0.6, 95% CI 0.4-0.9) and bacille Calmette Guerin (BCG)
      vaccinated contacts (aOR 0.06, 95% CI 0.04-0.09). Among BCG-vaccinated contacts,
      the proportion screened increased from 9% in 2008 to 43% in 2011 (p-value for
      trend <0.001). LTBI diagnosis among contacts screened was associated with non
      Dutch nationality (aOR 2.8, 95% CI 1.9-4.1) and being a close contact (aOR 4.0,
      95% CI 1.9-8.3). Of the 254 contacts with LTBI diagnosis, 142 (56%) started
      preventive treatment. Starting treatment was associated with Dutch nationality
      (aOR 2.6, 95% CI 1.2-5.4) and being a close contact (aOR 10.5, 95% CI 1.5-70.7).
      Treatment completion was achieved by 129 (91%) of the 142 contacts who started
      treatment. Two areas for improvement were identified: further expanding LTBI
      screening, particularly among BCG-vaccinated contacts and contacts of sputum
      smear-negative index patients, and expanding preventive treatment among contacts
      with LTBI. 

PMID- 25063247
TI  - Changes in physical activity and all-cause mortality in COPD.
AB  - Little is known about changes in physical activity in subjects with chronic
      obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we
      aimed to study changes in physical activity in subjects with and without COPD and
      the impact of physical activity on mortality risk. Subjects from the Copenhagen
      City Heart Study with at least two consecutive examinations were selected. Each
      examination included a self-administered questionnaire and clinical examination.
      1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1
      s 67+/-18 and 91+/-15% predicted, respectively) were included. COPD subjects with
      moderate or high baseline physical activity who reported low physical activity
      level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35,
      respectively; both p<0.001). In COPD subjects with low baseline physical
      activity, no differences were found in survival between unchanged or increased
      physical activity at follow-up. In addition, subjects without COPD with low
      physical activity at follow-up had the highest hazard ratio of mortality,
      irrespective of baseline physical activity level (p<=0.05). A decline to low
      physical activity at follow-up was associated with an increased mortality risk in
      subjects with and without COPD. These observational data suggest that it is
      important to assess and encourage physical activity in the earliest stages of
      COPD in order to maintain a physical activity level that is as high as possible,
      as this is associated with better prognosis. 

PMID- 25063248
TI  - Matrix metalloproteinase-7 A-181G and its interaction with matrix
      metalloproteinase-9 C-1562T polymorphism in preeclamptic patients: association
      with malondialdehyde level and severe preeclampsia.
AB  - PURPOSE: The abnormal activation of matrix metalloproteinases (MMPs) during
      pregnancy might be involved in the pathogenesis of preeclampsia. The aim of
      present study was to investigate the possible influence of MMP-7 A-181G and its
      interaction with MMP-9 C- 1562T polymorphism on the risk of preeclampsia and
      lipid peroxidation level. METHODS: In a case-control study the MMP-7 A-181G and
      MMP-9 C-1562T polymorphisms were studied in 168 preeclamptic and 154 healthy
      pregnant women from Western Iran. The MMP-7 and-9 genotypes were detected using
      polymerase chain reaction-restriction fragment length polymorphism method.
      RESULTS: The frequency of MMP-7 G allele in mild- (37.4 %) and severe
      preeclampsia (45.6 %) and controls (40.3 %) were not significantly different. In
      preeclamptic patients in the presence of MMP-7 AG + GG genotype there was a
      significantly higher concentration of malondialdehyde (MDA) (10.52 +/- 4.18 MUM,
      p = 0.017) compared to that in AA genotype carriers (9 +/- 2.89 MUM). Also, in
      the presence of both MMP-7 G and MMP-9 T alleles the MDA concentration (11.6 +/-
      4.9 MUM) was significantly higher compared to the concomitant presence of MMP-7 A
      and MMP-9 C wild alleles (9.2 +/- 3.1 MUM, p = 0.02). There was an interaction
      between two alleles of MMP-7 G and MMP-9 T that significantly increased the risk
      of severe preeclampsia by 1.4-fold (OR = 1.4, 95 % CI = 1.06-1.85, p = 0.016).
      CONCLUSIONS: The present study indicates lack of a direct influence of MMP-7 A
      181G polymorphism on the risk of preeclampsia. However, this polymorphism through
      elevation of MDA level as a marker of lipid peroxidation and interaction with MMP
      9 C-1562T polymorphism might be associated with the risk of severe preeclampsia.

PMID- 25063249
TI  - Management of adnexal masses in pregnancy: our experience from a tertiary
      referral perinatal centre in South India.
AB  - PURPOSE: Adnexal masses in pregnancy are often incidentally detected during
      sonography and most resolve spontaneously by early second trimester. This study
      aimed to look at the prevalence and management of adnexal masses in pregnancy at
      a tertiary care referral perinatal hospital. METHODS: This is a retrospective
      study of all women with adnexal masses (excluding ectopic gestations and non
      gynaecological lesions) identified pre-pregnancy or during pregnancy
      (antepartum/intrapartum) from January 2006 to August 2013 at the study institute.
      RESULTS: The study identified 252 women (0.6, 95 %, CI: 0.5, 0.7) with adnexal
      masses and mean (SD range) age of 27.1 (4.21, 18-39) years. Majority (80 %) of
      the masses were diagnosed incidentally. 170 (67.5 %) women were offered
      conservative management and cysts resolved in half of them. 87 (34.5 %) women had
      adnexal surgery and 15.1 % were operated during the antepartum period because of
      persistent abdominal pain or suspicious sonographic findings. Three (1.2 %)
      malignancies and five (2.0 %) borderline ovarian tumours were diagnosed on
      histopathological examination. 16 (6.3 %) women were lost to follow-up
      antenatally. Pregnancy carried to term in 175 (69.4 %) women. Perinatal mortality
      rate was 31.1/1,000 total births (caused by prematurity). Complications
      encountered were torsion (7.1 %), malignancy (1.2 %), rupture (0.4 %) and
      infection (0.4 %). CONCLUSION: Although conservative management was appropriate
      in the majority of cases, the study identifies the need to standardize diagnosis,
      investigations and management for a better evaluation of outcomes.

PMID- 25063250
TI  - Expression of hypoxia-regulated genes and glycometabolic genes in placenta from
      patients with intrahepatic cholestasis of pregnancy.
AB  - INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder
      unique to pregnancy that is associated with increased rates of fetal distress and
      demise. While acute hypoxia is believed to cause the pathophysiology of ICP,
      direct molecular evidence for this is lacking. Here, we analyzed expression of
      three hypoxia-regulated genes and several of their downstream target genes
      involved in glucose metabolism in placenta. METHODS: Placental tissue was
      collected from 20 women with normal pregnancies and 20 women with ICP. RNA and
      protein levels of hypoxia inducible transcription factors -1alpha (HIF-1alpha),
      development and DNA protein damage response 1 (REDD1), mammalian target of
      rapamycin (mTOR), glucose transporter type 1 (GLUT1), phosphoglycerate kinase1
      (PGK1) and lacticdehydrogenase (LDHA) in placental tissue were measured by
      reverse transcriptase real time PCR and Western Blot. Proteins were also located
      by immunohistochemistry. RESULTS: Transcript levels were similar for all genes
      between the two types of placental tissue. In contrast, all protein levels except
      that of mTOR were significantly higher in placentas from ICP patients than the
      controls (P < 0.05). All proteins localized to the cytotrophoblast and
      syncytiotrophoblast. DISCUSSION: The placenta from ICP patients is more
      vulnerable to acute hypoxia and ischemia reperfusion injury. In response to
      hypoxia stress and oxidative damage in ICP, the placenta activates HIF-1alpha and
      REDD1, which in turn may up-regulates glucose transport and anaerobic glycolysis.
      CONCLUSIONS: HIF-1alpha, REDD1 and mTOR may play a significant role in the
      reaction to hypoxia and oxidative stress and regulate glucose metabolism in the
      placenta of ICP patients.

PMID- 25063251
TI  - Maternal plasma levels of cell-free beta-HCG mRNA as a prenatal diagnostic
      indicator of placenta accrete.
AB  - OBJECTIVE: Several biomarkers, including maternal serum creatinine kinase and
      alpha-fetoprotein, have been described as potential tools for the diagnosis of
      placental abnormalities. This study aimed to determine whether maternal plasma
      mRNA levels of the beta subunit of human chorionic gonadotropin (beta-HCG) could
      predict placenta accreta prenatally. METHODS: Sixty-eight singleton pregnant
      women with prior cesarean deliveries (CDs) were classified into three groups:
      normal placentation (35 women, control group); placenta previa alone (21 women,
      placenta previa group); and both placenta previa and placenta accreta (12 women,
      placenta previa/accreta group). Maternal plasma concentrations of cell-free beta
      HCG mRNA were measured by real-time reverse-transcription polymerase chain
      reaction and were expressed as multiples of the median (MoM). RESULTS: Cell-free
      beta-HCG mRNA concentrations (MoM, range) were significantly higher in women with
      placenta accreta (3.65, 2.78-7.19) than in women with placenta previa (0.94, 0.00
      2.97) or normal placentation (1.00, 0.00-2.69) (Steel-Dwass test, P < 0.01 and P
      < 0.01, respectively). In the placenta previa/accreta group, the concentration of
      cell-free beta-HCG mRNA was significantly higher among women who underwent CDs
      with hysterectomy (4.41, 3.49-7.19) than among women whose CDs did not result in
      hysterectomy (3.20, 2.78-3.70) (Mann-Whitney U test, P = 0.012). DISCUSSION: An
      increased level of cell-free beta-HCG mRNA in the maternal plasma of women with
      placenta accreta may arise from direct uteroplacental transfer of cell-free
      placental mRNA molecules. CONCLUSIONS: The concentration of cell-free beta-HCG
      mRNA in maternal plasma may be applicable to the prenatal diagnosis of placenta
      accreta, especially to identify women with placenta accreta likely to require
      hysterectomy.

PMID- 25063252
TI  - Pharmacists and physicians get smart about antibiotics: a prescription for
      change.

PMID- 25063253
TI  - Nonprescription naloxone: pros and cons.

PMID- 25063254
TI  - APhA House of Delegates: ensuring the power and promise of pharmacy.

PMID- 25063255
TI  - Medicare Annual Wellness Visits: patient need and pharmacist patient care
      services intersect.

PMID- 25063257
TI  - Report of the 2014 APhA House of Delegates.

PMID- 25063256
TI  - 2014 Prescott Lecture: designed to fail, reengineered to succeed.

PMID- 25063260
TI  - Variability in compounding of oral liquids for pediatric patients: a patient
      safety concern.
AB  - OBJECTIVE: To determine the degree in variation of oral liquid pediatric
      compounding practices in Michigan pharmacies. DESIGN: Cross-sectional survey
      study. SETTING: All types of inpatient and outpatient pharmacies across the state
      of Michigan, excluding nuclear pharmacies and long-term care facilities.
      PARTICIPANTS: 244 Michigan pharmacies. INTERVENTION: An online survey tool was
      used to assess the current compounding practices of 147 oral liquid pediatric
      medications. The survey was e-mailed or faxed to hospitals, chain pharmacies, and
      independent pharmacies. Pharmacists were also mailed a follow-up postcard, and
      the Michigan Pharmacists Association publicized the project through its journal
      and annual meeting. MAIN OUTCOME MEASURES: Pharmacy demographics; number of
      compounding pharmacies; number of medications compounded; awareness of
      compounding errors; results of compounding errors; and number of concentrations
      compounded per medication. RESULTS: The majority of respondents were from
      outpatient pharmacies, but inpatient and other types of pharmacies were also
      represented. The majority of participating pharmacies compound fewer than five
      oral liquid medications per week. Awareness of errors was low overall, with no
      errors believed to result in permanent harm or death. The number of
      concentrations compounded per medication ranged from 1 to 9, with the majority of
      pharmacies compounding more than 3 concentrations per medication. CONCLUSION:
      There is a considerable degree of variation in current oral pediatric liquid
      compounding practices in Michigan pharmacies. This variability poses a
      significant risk to patient safety.

PMID- 25063261
TI  - Kentucky pharmacists' opinions of the potential reclassification of
      pseudoephedrine as a legend drug.
AB  - OBJECTIVES: To collect and analyze Kentucky pharmacists' opinions of the
      effectiveness of current methamphetamine precursor controls, to analyze proposed
      legislation to make pseudoephedrine (PSE) a legend drug, and to analyze the
      potential impact of such legislation on pharmacy practice and patients. DESIGN:
      Descriptive, nonexperimental survey study. SETTING: Kentucky; June through
      October 2012. PARTICIPANTS: 431 Kentucky community pharmacists. INTERVENTION:
      Mailed survey. MAIN OUTCOME MEASURES: Perceived efficacy of current
      methamphetamine precursor controls, anticipated impact on individual pharmacy
      practices and patients of proposed legislation to make PSE available by
      prescription only, and current opinions about the proposed legislation. RESULTS:
      Analysis of 431 community pharmacists showed that approximately 77% believed
      proposed legislation to make PSE available by prescription only would be
      effective in reducing methamphetamine abuse and methamphetamine-related
      laboratory incidents, with 56.2% indicating support for the proposed legislation.
      Pharmacists practicing in chain pharmacies were 2.9 times more likely to support
      the legislation than pharmacists practicing in independent pharmacies. Additional
      factors influencing pharmacist support included Kentucky region of practice,
      anticipated impact on time spent on PSE activities, pharmacy profit,
      methamphetamine abuse, and methamphetamine-related laboratory incidents.
      Pharmacists practicing in regions of Kentucky associated with higher
      methamphetamine abuse appear to more strongly support the proposed legislation.
      CONCLUSION: Pharmacists are at the frontline of PSE distribution. Gaining a
      better understanding of issues surrounding the distribution of PSE will enhance
      the likelihood that future legislation may be crafted to reduce methamphetamine
      production, laboratory incidents, and abuse while minimizing inconvenience and
      cost.

PMID- 25063262
TI  - Analysis of the accuracy and readability of herbal supplement information on
      Wikipedia.
AB  - OBJECTIVE: To determine the completeness and readability of information found in
      Wikipedia for leading dietary supplements and assess the accuracy of this
      information with regard to safety (including use during pregnancy/lactation),
      contraindications, drug interactions, therapeutic uses, and dosing. DESIGN: Cross
      sectional analysis of Wikipedia articles. INTERVENTIONS: The contents of
      Wikipedia articles for the 19 top-selling herbal supplements were retrieved on
      July 24, 2012, and evaluated for organization, content, accuracy (as compared
      with information in two leading dietary supplement references) and readability.
      MAIN OUTCOME MEASURES: Accuracy of Wikipedia articles. RESULTS: No consistency
      was noted in how much information was included in each Wikipedia article, how the
      information was organized, what major categories were used, and where safety and
      therapeutic information was located in the article. All articles in Wikipedia
      contained information on therapeutic uses and adverse effects but several lacked
      information on drug interactions, pregnancy, and contraindications. Wikipedia
      articles had 26%-75% of therapeutic uses and 76%-100% of adverse effects listed
      in the Natural Medicines Comprehensive Database and/or Natural Standard. Overall,
      articles were written at a 13.5-grade level, and all were at a ninth-grade level
      or above. CONCLUSION: Articles in Wikipedia in mid-2012 for the 19 top-selling
      herbal supplements were frequently incomplete, of variable quality, and sometimes
      inconsistent with reputable sources of information on these products. Safety
      information was particularly inconsistent among the articles. Patients and health
      professionals should not rely solely on Wikipedia for information on these herbal
      supplements when treatment decisions are being made.

PMID- 25063263
TI  - Development and implementation of a pharmacist-delivered Medicare annual wellness
      visit at a family practice office.
AB  - OBJECTIVE: To describe the development and implementation of a pharmacist
      delivered Medicare Annual Wellness Visit (MWV). SETTING: Physician-owned, private
      family practice office. PRACTICE INNOVATION: Pharmacist-delivered MWV. MAIN
      OUTCOME MEASURES: Patient visits and practice income. RESULTS: Because of time
      constraints in the practice, physicians, nurse practitioners, and a physician
      assistant had been unable to offer MWVs, a new service available to Medicare
      beneficiaries under the Affordable Care Act. A pharmacist who was previously
      providing patient care services 1 day/week at a fixed hourly rate was able to add
      an additional 1 day/week for provision of MWVs. These visits involve updating
      medical and medication histories; measuring weight, mass, and blood pressure;
      assessing cognitive and physical function; and screening the patient and
      recommending preventive services. From September 2012 to February 2013, 174
      patients participated in the pharmacist-delivered MWV. Pharmacist visits were
      billed using codes G0438 and G0439, and the practice realized a positive net
      income for the MWVs. CONCLUSION: Pharmacist-delivered MWVs are financially viable
      and allow for greater pharmacist participation on the primary care team.

PMID- 25063264
TI  - Financial implications of pharmacist-led Medicare annual wellness visits.
AB  - OBJECTIVE: To determine if pharmacist-led Medicare Annual Wellness Visits (AWVs)
      are a feasible mechanism to financially support a pharmacist position in
      physicians' offices. SETTING: Large, teaching, ambulatory clinic in North
      Carolina. PRACTICE DESCRIPTION: The Mountain Area Health Education Family Health
      Center is a family medicine practice that houses a large medical residency
      program. The Department of Pharmacotherapy comprises five pharmacists and two
      pharmacy residents providing direct patient care. PRACTICE INNOVATION: In April
      2012, pharmacists began conducting Medicare AWVs for patients referred by their
      primary care physicians within the practice. MAIN OUTCOME MEASURES: Visit
      reimbursement, annual revenue, number of patients who must be seen to cover the
      cost of a pharmacist's salary. RESULTS: A small practice requires all eligible
      Medicare patients to complete an AWV to generate enough revenue to support a new
      pharmacist position. A medium-sized practice requires a 54% utilization rate, and
      a large practice requires an 18% utilization rate. Two additional AWVs per half
      day of clinic are needed to support an existing pharmacotherapy clinic. A total
      of 1,070 AWVs per year are required to support a pharmacist's salary, regardless
      of practice size. CONCLUSIONS: AWV reimbursement may significantly contribute to
      supporting the cost of a pharmacist, particularly in medium- to large-sized
      practices. In larger practices, enough revenue can be generated to support the
      cost of multiple pharmacists.

PMID- 25063265
TI  - How gaps in regulation of compounding pharmacy set the stage for a multistate
      fungal meningitis outbreak.
AB  - OBJECTIVE: To provide an overview of the regulation issues surrounding
      compounding pharmacy that allowed the United States fungal meningitis outbreak to
      occur and the changes in regulation that ensued. SUMMARY: In September 2012, a
      single case report sparked an investigation into a nationwide outbreak of fungal
      meningitis due to contaminated injectable drugs. The source of the contamination,
      New England Compounding Center (NECC), was in violation of several state and
      federal laws and had a history of such violations. The regulation of compounding
      pharmacies has historically been left to the states, while manufacturing fell
      under the jurisdiction of the Food and Drug Administration. However, as more
      compounders took part in large-scale interstate distribution of drugs, the
      current state-based regulatory system became less equipped to provide oversight.
      The lack of a clear definition of "compounding pharmacy" further obscures proper
      oversight and regulation. Congress and several states have taken steps to build
      safeguards against large-scale compounding by increasing inspections, adopting
      stricter licensing requirements, and enacting the Drug Quality and Security Act
      of 2013. CONCLUSION: While the current compounding regulation changes are a
      necessary step forward, it remains to be seen how effective they will be in
      safeguarding the public.

PMID- 25063266
TI  - Inflammatory chronic diseases: preventable by vaccines?

PMID- 25063267
TI  - Umeclidinium bromide/vilanterol trifenatate, perampanel, and eslicarbazepine
      acetate.

PMID- 25063268
TI  - How can 'we' make health care better?

PMID- 25063269
TI  - Psychometric comparison of three behavioural scales for the assessment of pain in
      critically ill patients unable to self-report.
AB  - INTRODUCTION: Pain assessment is associated with important outcomes in ICU
      patients but remains challenging, particularly in non-communicative patients. Use
      of a reliable tool is paramount to allow any implementation of sedation/analgesia
      protocols in a multidisciplinary team. This study compared psychometric
      properties (inter-rater agreement primarily; validity, responsiveness and
      feasibility secondarily) of three pain scales: Behavioural Pain Scale (BPS/BPS
      NI, that is BPS for Non-Intubated patients), Critical Care Pain Observation Tool
      (CPOT) and Non-verbal Pain Scale (NVPS), the pain tool routinely used in this 16
      bed medical ICU. METHODS: Pain was assessed by at least one of four investigators
      and one of the 20 bedside nurses before, during and 10 minutes after routine care
      procedures in non-comatose patients (Richmond Agitation Sedation Scale >= -3) who
      were unable to self-report their pain intensity. The Confusion Assessment Method
      for the ICU was used to assess delirium. Non-parametric tests were used for
      statistical analysis. Quantitative data are presented as median (25th to 75th).
      RESULTS: A total of 258 paired assessments of pain were performed in 30 patients
      (43% lightly sedated, 57% with delirium, 63% mechanically ventilated). All three
      scales demonstrated good psychometric properties. However, BPS and CPOT exhibited
      the best inter-rater reliability (weighted-kappa 0.81 for BPS and CPOT) and the
      best internal consistency (Cronbach-alpha 0.80 for BPS, 0.81 for CPOT), which
      were higher than for NVPS (weighted-kappa 0.71, P <0.05; Cronbach-alpha 0.76, P
      <0.01). Responsiveness was significantly higher for BPS compared to CPOT and for
      CPOT compared to NVPS. For feasibility, BPS was rated as the easiest scale to
      remember but there was no significant difference in regards to users' preference.
      CONCLUSIONS: BPS and CPOT demonstrate similar psychometric properties in non
      communicative intubated and non-intubated ICU patients.

PMID- 25063270
TI  - Role of cognitive enhancer therapy in Alzheimer's disease with concomitant
      cerebral white matter disease: findings from a long-term naturalistic study.
AB  - BACKGROUND: Evidence is lacking for cognitive enhancer therapy in patients with
      Alzheimer's disease (AD) and concomitant cerebrovascular disease (mixed AD) as
      such patients would have been excluded from clinical trials. Earlier studies of
      mixed AD have focused on large vessel cerebrovascular disease. The influence of
      small vessel cerebrovascular disease (svCVD) in the form of white matter
      hyperintensity (WMH) on treatment outcomes in mixed AD has not been addressed.
      OBJECTIVE: In this long-term naturalistic study, we evaluated the effectiveness
      of cognitive enhancers in patients with mixed AD with svCVD. METHODS: We
      conducted a retrospective analysis of a prospective clinical database from a
      memory clinic of a tertiary hospital. Magnetic resonance imaging WMH was used as
      a marker of svCVD. Demographic, cognitive, and treatment data were analysed.
      Linear mixed models with patient-specific random effects were used to evaluate
      cognitive outcomes over time while adjusting for confounders. RESULTS: Patients
      with mixed AD (n = 137) or AD without svCVD (pure AD) (n = 28) were studied over
      a median duration of 28.7 months. Patients with mixed AD had a higher prevalence
      of hypertension (62.8 vs. 35.7 %, p = 0.011). The majority (75.2 %) of the study
      sample were managed with monotherapy. Mini Mental State Examination (MMSE) scores
      decreased over time (-0.04, p = 0.007), and the decrease was similar for both
      diagnosis groups (-0.03, p = 0.246). Annual estimated mean MMSE decline was 0.84
      for pure AD and 0.48 for mixed AD. Similar trends were observed with Montreal
      Cognitive Assessment (MoCA) scores, with annual estimated mean reduction of 0.72
      and 0.48 for pure AD and mixed AD, respectively. CONCLUSION: Cognitive enhancers
      are effective in slowing the rate of cognitive decline in patients with AD with
      svCVD. These findings would need to be confirmed in randomized clinical trials.

PMID- 25063271
TI  - Usefulness of antiemetic therapy with aprepitant, palonosetron, and dexamethasone
      for lung cancer patients on cisplatin-based or carboplatin-based chemotherapy.
AB  - PURPOSE: The purpose of the study is to investigate the usefulness of the triplet
      regimen comprising aprepitant, palonosetron, and dexamethasone in patients
      treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic
      chemotherapy (MEC). METHODS: Patients with lung cancer (aged 65.8 +/- 8.4 years)
      who received carboplatin-based MEC and those treated with cisplatin-based HEC
      were enrolled. The antiemetic regimen for both types of chemotherapy consisted of
      aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines
      prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy
      induced nausea and vomiting (CINV) and the use of salvage treatment were
      assessed. The primary endpoints were the percentage of patients with a complete
      response (CR: no nausea and no salvage treatment) during the entire study period
      (5 days) after chemotherapy, during the acute phase (day 1), and during the
      delayed phase (days 2-5). RESULTS: CR rates for the entire period were 86 and 71%
      in patients receiving carboplatin-based and cisplatin-based chemotherapy,
      respectively. CR rates were respectively 98 and 100% in the acute phase versus 87
      and 71% in the delayed phase. Most of the patients could ingest food throughout
      the entire period after chemotherapy. Assessment of various risk factors for
      acute and delayed CINV (gender, age, prior vomiting due to antineoplastic
      therapy, prior experience of motion sickness, and history of drinking) revealed
      no significant influence of these factors on the CR rate for the entire period in
      patients receiving either carboplatin-based or cisplatin-based chemotherapy.
      CONCLUSION: The present triple therapy can be recommended for supporting both
      carboplatin-based and cisplatin-based chemotherapy regimens.

PMID- 25063272
TI  - Improving national hospice/palliative care service symptom outcomes
      systematically through point-of-care data collection, structured feedback and
      benchmarking.
AB  - PURPOSE: Every health care sector including hospice/palliative care needs to
      systematically improve services using patient-defined outcomes. Data from the
      national Australian Palliative Care Outcomes Collaboration aims to define whether
      hospice/palliative care patients' outcomes and the consistency of these outcomes
      have improved in the last 3 years. METHODS: Data were analysed by clinical phase
      (stable, unstable, deteriorating, terminal). Patient-level data included the
      Symptom Assessment Scale and the Palliative Care Problem Severity Score.
      Nationally collected point-of-care data were anchored for the period July
      December 2008 and subsequently compared to this baseline in six 6-month reporting
      cycles for all services that submitted data in every time period (n = 30) using
      individual longitudinal multi-level random coefficient models. RESULTS: Data were
      analysed for 19,747 patients (46 % female; 85 % cancer; 27,928 episodes of care;
      65,463 phases). There were significant improvements across all domains (symptom
      control, family care, psychological and spiritual care) except pain.
      Simultaneously, the interquartile ranges decreased, jointly indicating that
      better and more consistent patient outcomes were being achieved. CONCLUSION:
      These are the first national hospice/palliative care symptom control performance
      data to demonstrate improvements in clinical outcomes at a service level as a
      result of routine data collection and systematic feedback.

PMID- 25063273
TI  - PPARbeta/delta prevents endoplasmic reticulum stress-associated inflammation and
      insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism.
AB  - AIM/HYPOTHESIS: Endoplasmic reticulum (ER) stress, which is involved in the link
      between inflammation and insulin resistance, contributes to the development of
      type 2 diabetes mellitus. In this study, we assessed whether peroxisome
      proliferator-activated receptor (PPAR)beta/delta prevented ER stress-associated
      inflammation and insulin resistance in skeletal muscle cells. METHODS: Studies
      were conducted in mouse C2C12 myotubes, in the human myogenic cell line LHCN-M2
      and in skeletal muscle from wild-type and PPARbeta/delta-deficient mice and mice
      exposed to a high-fat diet. RESULTS: The PPARbeta/delta agonist GW501516
      prevented lipid-induced ER stress in mouse and human myotubes and in skeletal
      muscle of mice fed a high-fat diet. PPARbeta/delta activation also prevented
      thapsigargin- and tunicamycin-induced ER stress in human and murine skeletal
      muscle cells. In agreement with this, PPARbeta/delta activation prevented ER
      stress-associated inflammation and insulin resistance, and glucose-intolerant
      PPARbeta/delta-deficient mice showed increased phosphorylated levels of inositol
      requiring 1 transmembrane kinase/endonuclease-1alpha in skeletal muscle. Our
      findings demonstrate that PPARbeta/delta activation prevents ER stress through
      the activation of AMP-activated protein kinase (AMPK), and the subsequent
      inhibition of extracellular-signal-regulated kinase (ERK)1/2 due to the
      inhibitory crosstalk between AMPK and ERK1/2, since overexpression of a dominant
      negative AMPK construct (K45R) reversed the effects attained by PPARbeta/delta
      activation. CONCLUSIONS/INTERPRETATION: Overall, these findings indicate that
      PPARbeta/delta prevents ER stress, inflammation and insulin resistance in
      skeletal muscle cells by activating AMPK.

PMID- 25063275
TI  - Diabetes and bone fracture: risk factors for old and young.
AB  - Diabetes mellitus may affect bone turnover in a number of ways, thus leading to
      impaired bone quality and a consequent increase in fracture risk. These factors
      are summarised in this commentary. 

PMID- 25063274
TI  - Glucagon regulates orexin A secretion in humans and rodents.
AB  - AIMS/HYPOTHESIS: Orexin A (OXA) modulates food intake, energy expenditure, and
      lipid and glucose metabolism. OXA regulates the secretion of insulin and
      glucagon, while glucose regulates OXA release. Here, we evaluate the role of
      glucagon in regulating OXA release both in vivo and in vitro. METHODS: In a
      double-blind crossover study, healthy volunteers and type 1 diabetic patients
      received either intramuscular glucagon or placebo. Patients newly diagnosed with
      type 2 diabetes underwent hyperinsulinaemic-euglycaemic clamp experiments, and
      insulin-hypoglycaemia tests were performed on healthy volunteers. The primary
      endpoint was a change in OXA levels after intramuscular glucagon or placebo
      administration in healthy participants and patients with type 1 diabetes.
      Secondary endpoints included changes in OXA in healthy participants during
      insulin tolerance tests and in patients with type 2 diabetes under
      hyperinsulinaemic-euglycaemic conditions. Participants and staff conducting
      examinations and taking measurements were blinded to group assignment. OXA
      secretion in response to glucagon treatment was assessed in healthy and obese
      mice, the streptozotocin-induced mouse model of type 1 diabetes, and isolated rat
      pancreatic islets. RESULTS: Plasma OXA levels declined in lean volunteers and in
      type 1 diabetic patients injected with glucagon. OXA levels increased during
      hyperinsulinaemic hypoglycaemia testing in healthy volunteers and during
      hyperinsulinaemic euglycaemic conditions in type 2 diabetic patients. Plasma OXA
      concentrations in healthy lean and obese mice and in a mouse model of type 1
      diabetes were lower after glucagon treatment, compared with vehicle control.
      Glucagon decreased OXA secretion from isolated rat pancreatic islets at both low
      and high glucose levels. OXA secretion declined in pancreatic islets exposed to
      diazoxide at high and low glucose levels, and after exposure to an anti-insulin
      antibody. Glucagon further reduced OXA secretion in islets pretreated with
      diazoxide or an anti-insulin antibody. CONCLUSIONS/INTERPRETATION: Glucagon
      inhibits OXA secretion in humans and animals, irrespective of changes in glucose
      or insulin levels. Through modifying OXA secretion, glucagon may influence energy
      expenditure, body weight, food intake and glucose metabolism.

PMID- 25063276
TI  - Membrane lipids protected from oxidation by red wine tannins: a proton NMR study.
AB  - Dietary polyphenols widespread in vegetables and beverages like red wine and tea
      have been reported to possess antioxidant properties that could have positive
      effects on human health. In this study, we propose a new in situ and non-invasive
      method based on proton liquid-state nuclear magnetic resonance (NMR) to determine
      the antioxidant efficiency of red wine tannins on a twice-unsaturated
      phospholipid, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLiPC), embedded in a
      membrane model. Four tannins were studied: (+)-catechin (C), (-)-epicatechin
      (EC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG). The
      lipid degradation kinetics was determined by measuring the loss of the bis
      allylic protons during oxidation induced by a radical initiator, 2,2'-Azobis(2
      methylpropionamidine) dihydrochloride (AAPH). The antioxidant efficiency, i.e.
      the ability of tannins to slow down the lipid oxidation rate, was shown to be
      higher for galloylated tannins, ECG and EGCG. Furthermore, the mixture of four
      tannins was more efficient than the most effective tannin, EGCG, demonstrating a
      synergistic effect. To better understand the antioxidant action mechanism of
      polyphenols on lipid membranes, the tannin location was investigated by NMR and
      molecular dynamics. A correlation between antioxidant action of tannins and their
      location at the membrane interface (inserted at the glycerol backbone level)
      could thus be established. 

PMID- 25063277
TI  - Immunological characterization of recombinant Wuchereria bancrofti cuticular
      collagen (COL-4) as putative vaccine candidate for human lymphatic filariasis.
AB  - OBJECTIVE: To elucidate immunoprophylactic potential of recombinant Wuchereria
      bancrofti (W. bancrofti) cuticular collagen (COL-4) in BALB/c mice and filarial
      clinical samples. METHODS: col-4 gene was PCR amplified from W. bancrofti L3 cDNA
      library and cloned in pRSET B vector. Recombinant COL-4 was over expressed in
      salt inducible system and was purified by nickel affinity chromatography. Humoral
      and cellular responses were measured by ELISA and peripheral blood mononuclear
      cells (PBMC) of various filarial clinical samples respectively using purified
      recombinant COL-4 antigen. Then the protective immune responses of COL-4
      immunized BALB/c mice were characterized. RESULTS: Sequence analysis of COL-4
      with human host proteins reveals lack of homology. The recombinant COL-4 was
      found to be at 15 kDa fusion protein. The affinity purified COL-4 showed
      significant reactivity with putatively immune sera and in a similar fashion it
      demonstrated marked proliferation in PBMC samples. Immunization studies in
      experimental filarial host (mice) elicited significant titers with protective
      antibody isotype profile (IgM and IgG). Cellular immune responses were also
      significant in terms of splenocytes proliferation assay on mice samples.
      CONCLUSIONS: Our immunological findings in experimental host suggest Th2 mediated
      immune response. Hence, we propose that W. bancrofti COL-4 could be an
      efficacious vaccine candidate against lymphatic filariasis.

PMID- 25063278
TI  - Discovery and design of cyclic peptides as dengue virus inhibitors through
      structure-based molecular docking.
AB  - OBJECTIVE: To find potential peptide inhibitors against the NS2B/NS3 protease of
      DENV which in turn, can inhibit the viral replication inside host cell. METHODS:
      Cyclic peptides were designed having combination of positively charged amino
      acids using ChemSketch software and were converted to 3D structures. DENV NS3
      protein structure was retrieved from Protein Data Bank (PDB) using PDB Id: 2FOM.
      DENV NS3 and cylic peptides were docked using MOE software after structural
      optimization. RESULTS: Through molecular docking it was revealed that most of the
      peptides bound deeply in the binding pocket of DENV NS2B/NS3 protease an had
      interactions with catalytic triad. Peptide 2 successfully blocked the catalytic
      triad of NS2B/NS3 protease. Peptide 1, 4 and 6 also had potential interactions
      with active residues of the NS2B/NS3 protease while all other peptides were in
      close contact with the active sites of NS2B/NS3 protease thus, these peptides can
      serve as a potential drug candidate to stop viral replication. CONCLUSIONS: Thus,
      it can be concluded from the study that these peptides could serve as important
      inhibitors to inhibit the viral replication and need further in-vitro
      investigations to confirm their efficacy.

PMID- 25063279
TI  - Molecular determination and genotyping of Cryptosporidium spp. in fecal and
      respiratory samples of industrial poultry in Iran.
AB  - OBJECTIVE: To identify the genotypes of prevalent Cryptosporidia in broiler
      chickens in Lorestan province, Iran. METHODS: A total of 1 000 fecal and 1 000
      trachea samples were collected from chickens. Smears from both fecal and tracheal
      samples were stained with modified Ziehl-Neelsen method and nested PCR-RFLP
      according to amplification of 18S rRNA gene using Ssp I and Vsp I restriction
      enzymes and DNA sequencing. RESULTS: From the examined chickens 0.7% was positive
      for Cryptosporidium. Infection was present in 0.5% fecal samples and also in 0.5%
      trachea. Only 0.3% of simultaneous infections in fecal and tracheal samples were
      observed. Nested PCR of our isolates demonstrated Cryptosporidium baileyi.
      CONCLUSIONS: In our work, low rate of Cryptosporidium baileyi infection was
      detected, but in critical situations and our poor management circumstances,
      cryptosporidiosis occurs in serious feature especially in immune suppressed
      individuals.

PMID- 25063280
TI  - Tissue tropism and parasite burden of Toxoplasma gondii RH strain in
      experimentally infected mice.
AB  - OBJECTIVE: To evaluate parasite distribution and tissue tropism of Toxoplasma
      gondii tachyzoites in experimentally infected mice using real time QPCR. METHODS:
      In this survey 16 Balb/c mice were inoculated with 1 * 10(4) alive tachyzoites of
      Toxoplasma gondii RH strain. After 1, 2, 3 days post infection and the last day
      (before death), different tissues of mice including blood, brain, eye, liver,
      spleen, kidney, heart and muscle were harvested. Following tissues DNA
      extraction, the parasite burden was quantified using real time QPCR targeting the
      B1 gene (451 bp). RESULTS: It showed that Toxoplasma after intraperitoneal
      injection was able to movement to various tissues in 24 hours. Parasite burden
      was high in all tissues but the most number of parasites were observed in kidney,
      heart and liver, respectively. CONCLUSIONS: These data provide significant
      baseline information about Toxoplasma pathogenesis, vaccine monitoring and drug
      efficiency.

PMID- 25063281
TI  - Prevalence of gastrointestinal helminthic infections and associated risk factors
      among schoolchildren in Tilili town, northwest Ethiopia.
AB  - OBJECTIVE: To determine the prevalence of gastrointestinal helminthes and
      associated risk factors among schoolchildren in Tilili town, northwest Ethiopia.
      METHODS: A cross-sectional study involving 385 schoolchildren was conducted
      between November 2011 to February 2012. Each student was selected using
      systematic random sampling method. Questionnaire and observation were used to
      identify socio-demographic and associated risk factors. Fresh stool samples were
      observed using formal-ether concentration technique. Data were analyzed using
      SPSS 16.0 statistical software. RESULTS: Four species of intestinal helminthes
      were identified with an overall prevalence of 44.2% (170 of 385 schoolchildren).
      The predominant parasites were Ascaris lumbricoides (A. lumbricoides) 153 (39.7%)
      and Trichuris trichiura (T. trichiura) 30 (7.8%). One hundred thirty five (35.1%)
      had single infections and 35 (9.2%) were infected with more than one helminthic
      parasites in which 32 (8.4%) were double infections and 3 (0.8%) were triple
      infections. Significant associations were observed between intestinal helminth
      infection and those of age, grade level, and school variables. Prevalence of
      hookworm infection was significant in children who did not wear shoes regularly
      (P<0.05). CONCLUSIONS: Intervention programs and education on personal and
      environmental hygiene should be implemented for the prevention and control of
      helminthic infections in the study area.

PMID- 25063282
TI  - Phenol content, antioxidant and tyrosinase inhibitory activity of mangrove plants
      in Micronesia.
AB  - OBJECTIVE: To find out and compare the in vitro antioxidant and tyrosinase
      inhibitory activities of two species of mangrove plants. METHODS: Mangrove
      samples were harvested at the shoreline on the island of Weno, Chuuk State in
      Micronesia. The phenol content, antioxidant activity (based on DPPH-free radical
      scavenging) and tyrosinase inhibitory activity in different tissues (leaves,
      barks and roots) of Rhizophora stylosa (R. stylosa) and Sonneratia alba (S.
      alba), collected from the island of Weno. RESULTS: Total phenol content ranged
      from 4.87 to 11.96 mg per g of freeze dried samples. The highest antioxidant
      activity was observed in R. stylosa bark (85.5%). The highest tyrosinase
      inhibitory activity was found in S. alba bark. Also, total phenol content and
      antioxidant activity were higher in methanol extracts than in aqueous extracts.
      CONCLUSIONS: Taken together, the results of this study proved that mangroves can
      be excellent sources of antioxidant compounds.

PMID- 25063283
TI  - Modulation of antioxidant status in streptozotocin-induced diabetic male Wistar
      rats following intake of red palm oil and/or rooibos.
AB  - OBJECTIVE: To investigate the role of red palm oil (RPO), rooibos tea extract
      (RTE) and their combined treatment (RPO + RTE) on antioxidant status in
      streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes mellitus was
      induced by a single administration of streptozotocin (50 mg/kg) and the rats were
      treated for 7 weeks. Antioxidant enzymes [catalase (CAT), glutathione peroxidase
      (GPx), superoxide dismutase (SOD)], antioxidant capacity [trolox equivalence
      antioxidant capacity (TEAC), oxygen radical absorbance capacity (ORAC)] as well
      as total protein, albumin, globulin, total glutathione, conjugated diene and
      thiobarbituric acid reactive substances (TBARS) were investigated. RESULTS:
      Treatment with RPO, RTE and RPO + RTE significantly (p>0.05) improved liver SOD
      and plasma ORAC in the diabetic rats. Similarly, diabetic rats treated with RTE
      and RPO + RTE enhanced liver GPx. A significant (P<0.05) increase in the plasma
      TBARS in the diabetic control group was observed when compared with the normal
      control group. Treatment of diabetic rats with RTE and RPO + RTE reduced plasma
      TBARS to a level not significantly different at P<0.05 from the normal control
      group. CONCLUSIONS: The results revealed the anti-oxidative potentials of red
      palm oil, rooibos and their combination in diabetic conditions and hence, they
      could be useful in the management of diabetes and its complications.

PMID- 25063284
TI  - Polyphenolic content and antioxidant activity of some wild Saudi Arabian
      Asteraceae plants.
AB  - OBJECTIVE: To study the antioxidant properties of crude extract of different
      Asteraceae plants. METHODS: The antioxidant properties of six extracts were
      evaluated using different antioxidant tests, including free radical scavenging,
      reducing power, metal chelation, superoxide anion radical scavenging, total
      antioxidant capacity and inhibition of lipid peroxidation activities. RESULTS:
      Picris cyanocarpa (P. cyanocarpa) and Anthemis deserti (A. deserti) had powerful
      antioxidant properties as radical scavenger, reducing agent and superoxide anion
      radical scavenger while Achillia fragrantissima (A. fragrantissima) and
      Artemissia monosperma (A. monosperma) were the most efficient as ion chelator
      (100% at 100, 200 and 400 MUg/mL) A. fragrantissima and Rhantarium appoposum (R.
      appoposum) showed 100% inhibition on peroxidation of linoleic acid emulsion at
      200 and 400 MUg/mL, while butylatedhydroxy toluene and ascorbic acid showed 100
      and 95% inhibition percentage at 400 MUg/mL, respectively. Those various
      antioxidant activities were compared to standard antioxidants such as butylated
      hydroxyl toluene and ascorbic acid. CONCLUSIONS: In most tests P. cyanocarpa and
      A. deserti had powerful antioxidant properties as radical scavenger, reducing
      agent and superoxide anion radical scavenger.

PMID- 25063285
TI  - DAPT suppresses the proliferation of human glioma cell line SHG-44.
AB  - OBJECTIVE: To explore the suppressing effect of gamma-secretase inhibitor DAPT on
      proliferation of human glioma cell line SHG-44 in vitro and its mechanism.
      METHODS: The SHG-44 cell was treated by DAPT with different concentration. The
      proliferation of cells was detected by MTT assay; cell cycle and TSC of CD133(+)
      were determined by flow cytometry analysis technique; the key factor in Notch
      signaling pathway (Notch-1, Delta-1, Hes-1) was measured by reverse transcriptase
      polymerase chain reaction and western blotting. RESULTS: DAPT inhibited the
      growth and proliferation of SHG-44 cells significantly(P<0.05). And the
      inhibiting effect on SHG-44 cells produced by DAPT showed a dose-dependent
      manner. DAPT increased the rate of cells in G0/G1 phase of SHG-44 cells, while it
      decreased the rate of cells in S phase. TSC of CD133(+) was significantly reduced
      after DAPT treated SHG-44 cells. The expression of protein and mRNA of Notch-1,
      Delta-1 and Hes-1 were gradually downregulated with the increase of DAPT doses.
      CONCLUSIONS: DAPT can downregulate these key factor in Notch signaling pathway,
      reduce the TSC of CD133+ and inhibit the proliferation of SHG-44 cells.

PMID- 25063286
TI  - Tissue factor expression and methylation regulation in differentiation of
      embryonic stem cells into trophoblast.
AB  - OBJECTIVE: To explore tissue factor (TF) expression and methylation regulation in
      differentiation of human embryonic stem cells (hESCs) into trophoblast. METHODS:
      Differentiation of hESCs into trophoblast was induced by bone morphogenetic
      protein 4 (BMP4). Expression of gene, protein of TF and DNA methylation at
      different time points during induction process was detected by RT-PCT, Western
      blot, flow cytometry and MSP-PCR method. RESULTS: The expression of mRNA, protein
      level of TF could be detected during directional differentiation of hESCs to
      trophoblast cells, semi methylation-semi non methylation expression appeared at
      TF DNA promoter region, and it showed decreased methylation level and increased
      non methylation level with formation of trophoblast cell and increased expression
      of TF. CONCLUSIONS: It shows that during differentiation of hESCs into
      trophoblast, the differential expression of TF is related with DNA methylation
      level, and it is changed with the methylation or non methylated degree. It
      provids new platform to furtherly explore the regulation mechanisms of specific
      expression of tissue factor in the process of the embryonic stem cell
      development.

PMID- 25063287
TI  - Effect of spinal cord extracts after spinal cord injury on proliferation of rat
      embryonic neural stem cells and Notch signal pathway in vitro.
AB  - OBJECTIVE: To investigate the effect of the spinal cord extracts (SCE) after
      spinal cord injuries (SCIs) on the proliferation of rat embryonic neural stem
      cells (NSCs) and the expressions of mRNA of Notch1 as well as of Hes1 in this
      process in vitro. METHODS: The experiment was conducted in 4 different mediums:
      NSCs+PBS (Group A-blank control group), NSCs+SCE with healthy SD rats (Group B
      normal control group), NSCs+SCE with SD rats receiving sham-operation treatment
      (Group C-sham-operation group) and NSCs+ SCE with SCIs rats (Group D-paraplegic
      group). Proliferative abilities of 4 different groups were analyzed by MTT
      chromatometry after co-culture for 1, 2, 3, 4 and 5 d, respectively. The
      expressions of Notch1 and Hes1 mRNA were also detected with RT-PCR after co
      culture for 24 and 48 h, respectively. RESULTS: After co-culture for 1, 2, 3, 4
      and 5 d respectively, the MTT values of group D were significantly higher than
      those of group A, group B and group C (P<0.05). However, there were no
      significantly differences regarding MTT values between group A, group B and group
      C after co-culture for 1, 2, 3, 4 and 5 d, respectively (P>0.05). Both the
      expressions of Notch1 and Hes1 mRNA of group D were significantly higher than
      those of other 3 groups after co-culture for 24 h and 48 h as well (P<0.05). But
      there was no difference oin expressions of Notch1 and Hes1 mRNA among group A,
      group B and group C after co-culture for 24 h and 48 h (P>0.05). There was no
      difference in expressions of Notch1 and Hes1 mRNA between 24 h and 48 h treatment
      in group D. CONCLUSIONS: SCE could promote the proliferation of NSCs. It is
      demonstrated that the microenvironment of SCI may promote the proliferation of
      NSCs. Besides, SCE could increase the expression of Notch1 and Hes1 mRNA of NSC.
      It can be concluded that the Notch signaling pathway activation is one of the
      mechanisms that locally injured microenvironment contributes to the proliferation
      of ENSC after SCIs. This process may be performed by up-regulating the
      expressions of Notch1 and Hes1 gene.

PMID- 25063288
TI  - Relationship between monocularly deprivation and amblyopia rats and visual system
      development.
AB  - OBJECTIVE: To explore the changes of lateral geniculate body and visual cortex in
      monocular strabismus and form deprived amblyopic rat, and visual development
      plastic stage and visual plasticity in adult rats. METHODS: A total of 60 SD rats
      ages 13 d were randomly divided into A, B, C three groups with 20 in each group,
      group A was set as the normal control group without any processing, group B was
      strabismus amblyopic group, using the unilateral extraocular rectus resection to
      establish the strabismus amblyopia model, group C was monocular form deprivation
      amblyopia group using unilateral eyelid edge resection + lid suture. At visual
      developmental early phase (P25), meta phase (P35), late phase (P45) and adult
      phase (P120), the lateral geniculate body and visual cortex area 17 of five rats
      in each group were exacted for C-fos Immunocytochemistry. Neuron morphological
      changes in lateral geniculate body and visual cortex was observed, the positive
      neurons differences of C-fos expression induced by light stimulation was measured
      in each group, and the condition of radiation development of P120 amblyopic adult
      rats was observed. RESULTS: In groups B and C, C-fos positive cells were
      significantly lower than the control group at P25 (P<0.05), there was no
      statistical difference of C-fos protein positive cells between group B and group
      A (P>0.05), C-fos protein positive cells level of group B was significantly lower
      than that of group A (P<0.05). The binoculus C-fos protein positive cells level
      of groups B and C were significantly higher than that of control group at P35,
      P45 and P120 with statistically significant differences (P<0.05). CONCLUSIONS:
      The increasing of C-fos expression in geniculate body and visual cortex neurons
      of adult amblyopia suggests the visual cortex neurons exist a certain degree of
      visual plasticity.

PMID- 25063289
TI  - Influenza virus H1N1 induced apoptosis of mouse astrocytes and the effect on
      protein expression.
AB  - OBJECTIVE: To investigate the effects of influenza A virus H1N1 infection on the
      proliferation and apoptosis of mouse astrocytes cells and its protein expression.
      METHODS: After mouse astrocytes was infected with purified influenza A virus H1N1
      in vitro, viral integration and replication status of the cells were detected by
      RT-PCR assay, cell proliferation and apoptosis was determined by MTT method and
      flow cytometry, respectively. Associated protein expression was detected by
      Western blotting. RESULTS: Agarose gel electrophoresis showed H1N1 virus can
      infect astrocytes and can be copied. MTT staining showed H1N1 virus infection can
      inhibit the proliferation of mouse astrocytes, which makes cell viability
      decreased significantly. Flow cytometry showed that the proportion of Annein V
      staining positive vascular endothelial cells in the influenza A virus group was
      significantly higher than that in the control group. Western blot analysis showed
      after 24 h and 32 h of infection, there were cells caspase-3 protein and the
      expression of its active form (lysed caspase-3 protein) increased. The proportion
      of Bax/Bcl-2 also increased. CONCLUSIONS: Influenza A virus can infect human
      vascular endothelial cells and proliferation and it can induce apoptosis of
      endothelial cells.

PMID- 25063290
TI  - Effect of Rougan Huaqian granules combined with human mesenchymal stem cell
      transplantation on liver fibrosis in cirrhosis rats.
AB  - OBJECTIVE: To observe the effect of Rougan Huaqian granules combined with human
      mesenchymal stem cell (hMSC) transplantation on the liver fibrosis in carbon
      tetrachloride-induced cirrhosis rats. METHODS: Sixty SD rats were randomly
      divided into five groups. The rats in control group received intraperitoneal
      injection of saline, while those in model control group, treatment group A, group
      B and group C received intraperitoneal injection of carbon tetrachloride oily
      solution to induce liver cirrhosis within 8 weeks. Then, the rats in the model
      control group, treatment group A, treatment group B, treatment group C received
      vein tail injection of saline, Rougan Huaqian granules, hMSC suspension and
      Rougan Huaqian granules combined with hMSC suspension. RESULTS: The treatment
      groups had significantly different liver function (AST levels), liver fibrosis
      index (laminin and HA), hepatic sinusoidal wallsalpha-smooth muscle actin, IV
      collagen and laminin protein expression and I, III collagen from the model group
      (P<0.05). The transplanted cells showed human hepatocyte-like cells
      differentiation trend in the liver. CONCLUSIONS: The Rougan Huaqian granules
      combined with hMSC transplantation can alleviate liver fibrosis in cirrhosis
      rats.

PMID- 25063291
TI  - Effect of pharmacological intervention on MIP-1alpha, MIP-1beta and MCP-1
      expression in patients with psoriasis vulgaris.
AB  - OBJECTIVE: To detect the expression level of macrophage inflammatory protein-1
      (MIP-1)alpha, MIP-1beta and monocyte chemoattractant protein-1 (MCP-1) in with
      psoriasis vulgaris and explore the role in the pathogenesis of psoriasis
      vulgaris. METHODS: The level of MIP-1alpha, MIP-1beta and MCP-1 in peripheral
      blood from 50 patients with psoriasis vulgaris and 50 normal controls were
      measured by enzyme linked immunosorbent assay. The correlation with psoriasis
      area and severity index (PASI) was analyzed. The level of MIP-1alpha, MIP-1beta
      and MCP-1 was compared between psoriasis vulgaris patients at active stage and
      resting stage. And the change in MIP-1alpha, MIP-1beta and MCP-1 before and after
      therapy was also observed. RESULTS: The content of MIP-1alpha, MIP-1beta and MCP
      1 in patients with psoriasis vulgaris was (1342.78 +/- 210.30), (175.28 +/-
      28.18) and (266.86 +/- 32.75) ng/L, respectively, significantly higher than those
      in control group (P<0.05). The expression level of MIP-1alpha, MIP-1beta and MCP
      1 in peripheral blood of patients with psoriasis vulgaris was positively
      correlated with PASI (P<0.01). After acitretin therapy, expression level of MIP
      1alpha, MIP-1beta and MCP-1 in peripheral blood of patients with psoriasis
      vulgaris was significantly decreased. CONCLUSIONS: Chemokine factor MIP-1alpha,
      MIP-1beta and MCP-1 may be involved in the pathogenesis of psoriasis vulgaris.

PMID- 25063292
TI  - Expression and significance of MMP-9 and MDM2 in the oncogenesis of lung cancer
      in rats.
AB  - OBJECTIVE: To observe the expression of matrix metalloproteinase-9 (MMP-9) and
      mouse double minute 2 homolog (MDM2) in the oncogenesis of lung cancer in rats
      and to explore their clinical value. METHODS: A total of 140 rats were selected,
      of which 20 were selected randomly as the control group; and the remaining 120 as
      the observation group. The observation group was injected with benzopyrene to
      establish diseases model such as tissue proliferation, abnormal proliferation and
      lung cancer. Detected the MMP-9 levels of lung tissue by enzyme-linked assay,
      detected the MDM2 levels of lung tissue by immunochemistry assay. RESULTS: The
      MMP-9 and MDM2 expression of the lung cancer group and the abnormal proliferation
      group were significantly higher than that in the tissue proliferation group and
      the control group, the difference was significant (P<0.05). And the MDM2
      expression of the tissue proliferation group was significantly higher than that
      in the control group, the difference was significant (P<0.05). There was no
      significant difference in the MMP-9 expression between the tissue proliferation
      group and the control group (P>0.05). The MDM2 and MMP-9 expression were
      increased in turn in the small cell carcinoma, squamous cell carcinoma and
      adenocarcinoma, the difference was statistically significant (P<0.05). The MMP-9
      and MDM2 expressions of stage III and stage IV lung cancer tissue in rats were
      significant higher than that during stage I and stage II, the difference was
      significant (P<0.05). There was no significantly different in the MMP-9 and MDM2
      expressions between stage III and stage IV(P>0.05), and there is no significant
      difference of the MMP-9 and MDM2 expressions between stage I and stage
      II(P>0.05). CONCLUSIONS: The expression of MMP-9 and MDM2 in lung tissue was
      associated with lung disease and lung cancer, both of them may be involved in the
      development and metastasis of lung cancer. Combined detection can be used as
      therapy and prognostic indicators for lung cancer.

PMID- 25063293
TI  - Quantifying sequence and structural features of protein-RNA interactions.
AB  - Increasing awareness of the importance of protein-RNA interactions has motivated
      many approaches to predict residue-level RNA binding sites in proteins based on
      sequence or structural characteristics. Sequence-based predictors are usually
      high in sensitivity but low in specificity; conversely structure-based predictors
      tend to have high specificity, but lower sensitivity. Here we quantified the
      contribution of both sequence- and structure-based features as indicators of RNA
      binding propensity using a machine-learning approach. In order to capture
      structural information for proteins without a known structure, we used homology
      modeling to extract the relevant structural features. Several novel and modified
      features enhanced the accuracy of residue-level RNA-binding propensity beyond
      what has been reported previously, including by meta-prediction servers. These
      features include: hidden Markov model-based evolutionary conservation, surface
      deformations based on the Laplacian norm formalism, and relative solvent
      accessibility partitioned into backbone and side chain contributions. We
      constructed a web server called aaRNA that implements the proposed method and
      demonstrate its use in identifying putative RNA binding sites. 

PMID- 25063294
TI  - Molecular basis of nucleotide-dependent substrate engagement and remodeling by an
      AAA+ activator.
AB  - Binding and hydrolysis of ATP is universally required by AAA+ proteins to
      underpin their mechano-chemical work. Here we explore the roles of the ATPase
      site in an AAA+ transcriptional activator protein, the phage shock protein F
      (PspF), by specifically altering the Walker B motif sequence required in
      catalyzing ATP hydrolysis. One such mutant, the E108Q variant, is defective in
      ATP hydrolysis but fully remodels target transcription complexes, the RNAP
      sigma(54) holoenzyme, in an ATP dependent manner. Structural analysis of the
      E108Q variant reveals that unlike wild-type protein, which has distinct
      conformations for E108 residue in the ATP and ADP bound forms, E108Q adapts the
      same conformation irrespective of nucleotide bound. Our data show that the
      remodeling activities of E108Q are strongly favored on pre-melted DNA and
      engagement with RNAP-sigma(54) using ATP binding can be sufficient to convert the
      inactive holoenzyme to an active form, while hydrolysis per se is required for
      nucleic acid remodeling that leads to transcription bubble formation.
      Furthermore, using linked dimer constructs, we show that RNAP-sigma(54)
      engagement by adjacent subunits within a hexamer are required for this protein
      remodeling activity while DNA remodeling activity can tolerate defective ATP
      hydrolysis of alternating subunits. 

PMID- 25063295
TI  - CRISPR-Cas: an efficient tool for genome engineering of virulent bacteriophages.
AB  - Bacteriophages are now widely recognized as major players in a wide variety of
      ecosystems. Novel genes are often identified in newly isolated phages as well as
      in environmental metavirome studies. Most of these novel viral genes have unknown
      functions but appear to be coding for small, non-structural proteins. To
      understand their biological role, very efficient genetic tools are required to
      modify them, especially in the genome of virulent phages. We first show that
      specific point mutations and large deletions can be engineered in the genome of
      the virulent phage 2972 using the Streptococcus thermophilus CRISPR-Cas Type II-A
      system as a selective pressure to increase recombination efficiencies. Of
      significance, all the plaques tested contained recombinant phages with the
      desired mutation. Furthermore, we show that the CRISPR-Cas engineering system can
      be used to efficiently introduce a functional methyltransferase gene into a
      virulent phage genome. Finally, synthetic CRISPR bacteriophage insensitive
      mutants were constructed by cloning a spacer-repeat unit in a low-copy vector
      illustrating the possibility to target multiple regions of the phage genome.
      Taken together, this data shows that the CRISPR-Cas system is an efficient and
      adaptable tool for editing the otherwise intractable genomes of virulent phages
      and to better understand phage-host interactions. 

PMID- 25063296
TI  - Sensitive, multiplex and direct quantification of RNA sequences using a modified
      RASL assay.
AB  - A sensitive and highly multiplex method to directly measure RNA sequence
      abundance without requiring reverse transcription would be of value for a number
      of biomedical applications, including high throughput small molecule screening,
      pathogen transcript detection and quantification of short/degraded RNAs. R NA A:
      nnealing, S: election and L: igation (RASL) assays, which are based on RNA
      template-dependent oligonucleotide probe ligation, have been developed to meet
      this need, but technical limitations have impeded their adoption. Whereas DNA
      ligase-based RASL assays suffer from extremely low and sequence-dependent
      ligation efficiencies that compromise assay robustness, Rnl2 can join a fully DNA
      donor probe to a 3'-diribonucleotide-terminated acceptor probe with high
      efficiency on an RNA template strand. Rnl2-based RASL exhibits sub-femtomolar
      transcript detection sensitivity, and permits the rational tuning of probe
      signals for optimal analysis by massively parallel DNA sequencing (RASL-seq). A
      streamlined Rnl2-based RASL-seq protocol was assessed in a small molecule screen
      using 77 probe sets designed to monitor complex human B cell phenotypes during
      antibody class switch recombination. Our data demonstrate the robustness, cost
      efficiency and broad applicability of Rnl2-based RASL assays.

PMID- 25063297
TI  - An archaeal family-B DNA polymerase variant able to replicate past DNA damage:
      occurrence of replicative and translesion synthesis polymerases within the B
      family.
AB  - A mutant of the high fidelity family-B DNA polymerase from the archaeon
      Thermococcus gorgonarius (Tgo-Pol), able to replicate past DNA lesions, is
      described. Gain of function requires replacement of the three amino acid loop
      region in the fingers domain of Tgo-Pol with a longer version, found naturally in
      eukaryotic Pol zeta (a family-B translesion synthesis polymerase). Inactivation
      of the 3'-5' proof-reading exonuclease activity is also necessary. The resulting
      Tgo-Pol Z1 variant is proficient at initiating replication from base mismatches
      and can read through damaged bases, such as abasic sites and thymine photo
      dimers. Tgo-Pol Z1 is also proficient at extending from primers that terminate
      opposite aberrant bases. The fidelity of Tgo-Pol Z1 is reduced, with a marked
      tendency to make changes at G:C base pairs. Together, these results suggest that
      the loop region of the fingers domain may play a critical role in determining
      whether a family-B enzyme falls into the accurate genome-replicating category or
      is an error-prone translesion synthesis polymerase. Tgo-Pol Z1 may also be useful
      for amplification of damaged DNA. 

PMID- 25063298
TI  - The multiMiR R package and database: integration of microRNA-target interactions
      along with their disease and drug associations.
AB  - microRNAs (miRNAs) regulate expression by promoting degradation or repressing
      translation of target transcripts. miRNA target sites have been catalogued in
      databases based on experimental validation and computational prediction using
      various algorithms. Several online resources provide collections of multiple
      databases but need to be imported into other software, such as R, for processing,
      tabulation, graphing and computation. Currently available miRNA target site
      packages in R are limited in the number of databases, types of databases and
      flexibility. We present multiMiR, a new miRNA-target interaction R package and
      database, which includes several novel features not available in existing R
      packages: (i) compilation of nearly 50 million records in human and mouse from 14
      different databases, more than any other collection; (ii) expansion of databases
      to those based on disease annotation and drug microRNAresponse, in addition to
      many experimental and computational databases; and (iii) user-defined cutoffs for
      predicted binding strength to provide the most confident selection. Case studies
      are reported on various biomedical applications including mouse models of alcohol
      consumption, studies of chronic obstructive pulmonary disease in human subjects,
      and human cell line models of bladder cancer metastasis. We also demonstrate how
      multiMiR was used to generate testable hypotheses that were pursued
      experimentally. 

PMID- 25063299
TI  - metaseq: a Python package for integrative genome-wide analysis reveals
      relationships between chromatin insulators and associated nuclear mRNA.
AB  - Here we introduce metaseq, a software library written in Python, which enables
      loading multiple genomic data formats into standard Python data structures and
      allows flexible, customized manipulation and visualization of data from high
      throughput sequencing studies. We demonstrate its practical use by analyzing
      multiple datasets related to chromatin insulators, which are DNA-protein
      complexes proposed to organize the genome into distinct transcriptional domains.
      Recent studies in Drosophila and mammals have implicated RNA in the regulation of
      chromatin insulator activities. Moreover, the Drosophila RNA-binding protein Shep
      has been shown to antagonize gypsy insulator activity in a tissue-specific
      manner, but the precise role of RNA in this process remains unclear. Better
      understanding of chromatin insulator regulation requires integration of multiple
      datasets, including those from chromatin-binding, RNA-binding, and gene
      expression experiments. We use metaseq to integrate RIP- and ChIP-seq data for
      Shep and the core gypsy insulator protein Su(Hw) in two different cell types,
      along with publicly available ChIP-chip and RNA-seq data. Based on the metaseq
      enabled analysis presented here, we propose a model where Shep associates with
      chromatin cotranscriptionally, then is recruited to insulator complexes in trans
      where it plays a negative role in insulator activity. 

PMID- 25063300
TI  - Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene
      network.
AB  - To enhance our knowledge regarding biological pathway regulation, we took an
      integrated approach, using the biomedical literature, ontologies, network
      analyses and experimental investigation to infer novel genes that could modulate
      biological pathways. We first constructed a novel gene network via a pairwise
      comparison of all yeast genes' Ontology Fingerprints--a set of Gene Ontology
      terms overrepresented in the PubMed abstracts linked to a gene along with those
      terms' corresponding enrichment P-values. The network was further refined using a
      Bayesian hierarchical model to identify novel genes that could potentially
      influence the pathway activities. We applied this method to the sphingolipid
      pathway in yeast and found that many top-ranked genes indeed displayed altered
      sphingolipid pathway functions, initially measured by their sensitivity to
      myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments
      confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4,
      encoding a palmitoyl transferase. Comparative analysis showed that few of these
      novel genes could be discovered by other existing methods. Our novel gene network
      provides a unique and comprehensive resource to study pathway modulations and
      systems biology in general.

PMID- 25063301
TI  - DNA bridging and looping by HMO1 provides a mechanism for stabilizing nucleosome
      free chromatin.
AB  - The regulation of chromatin structure in eukaryotic cells involves abundant
      architectural factors such as high mobility group B (HMGB) proteins. It is not
      understood how these factors control the interplay between genome accessibility
      and compaction. In vivo, HMO1 binds the promoter and coding regions of most
      ribosomal RNA genes, facilitating transcription and possibly stabilizing
      chromatin in the absence of histones. To understand how HMO1 performs these
      functions, we combine single molecule stretching and atomic force microscopy
      (AFM). By stretching HMO1-bound DNA, we demonstrate a hierarchical organization
      of interactions, in which HMO1 initially compacts DNA on a timescale of seconds,
      followed by bridge formation and stabilization of DNA loops on a timescale of
      minutes. AFM experiments demonstrate DNA bridging between strands as well as
      looping by HMO1. Our results support a model in which HMO1 maintains the
      stability of nucleosome-free chromatin regions by forming complex and dynamic DNA
      structures mediated by protein-protein interactions. 

PMID- 25063303
TI  - Peer effects in early childhood education: testing the assumptions of special
      education inclusion.
AB  - There has been a push in recent years for students with disabilities to be
      educated alongside their typically developing peers, a practice called inclusion.
      In this study, we sought to determine whether peer effects operate within early
      childhood special-education (ECSE) classrooms in which preschoolers with
      disabilities are educated alongside typical peers. Peer effects specific to
      language growth were assessed for 670 preschoolers (mean age = 52 months) in 83
      ECSE classrooms; 55% of the children had disabilities. We found that the average
      language skills of classmates, as assessed in the fall of the year, significantly
      predicted children's language skills in the spring (after controlling for their
      relative skill level in the fall); in addition, there was a significant
      interactive effect of disability status (i.e., the presence or absence of a
      disability) and peers' language skills. Peer effects were the least consequential
      for children without disabilities whose classmates had relatively strong language
      skills, and the most consequential for children with disabilities whose
      classmates had relatively poor language skills. 

PMID- 25063304
TI  - Augmented meaningful use criteria to identify patients eligible for lung cancer
      screening.
AB  - BACKGROUND: Lung cancer screening (LCS) with low-dose-radiation (low-dose
      computed tomography [LDCT]) saves lives. Despite recent US Preventive Services
      Task Force (USPTF) draft endorsement of LCS, a minority of eligible patients get
      screened. Meaningful use is a set of standards for electronic health records
      (EHR) established by the Centers for Medicare and Medicaid Services and includes
      reporting of smoking status. We sought to improve rates of LCS among patients
      treated at our institution by identifying eligible patients using augmented
      smoking-related meaningful use criteria. METHODS: We launched an LCS program at
      our institution, a National Comprehensive Cancer Network (NCCN) cancer center, in
      January 2013. We developed a "tobacco screen," administered by clinic staff to
      all adult outpatients every 6 months and entered into the EHR. This contained
      smoking-related meaningful use criteria as well as a pack-year calculation and
      quit date if applicable. Weekly electronic reports of patients who met
      eligibility criteria for LCS were generated, and EHR review excluded patients who
      had had chest computed tomography (CT) within 12 months or who were undergoing
      cancer treatment. We then contacted eligible patients to review eligibility for
      LCS and communicated with the primary treating physician regarding the plan for
      LCS. RESULTS: During the first 3 months of the program, 4 patients were enrolled,
      2 by physician referral and 2 by self-referral. We then began to use the tobacco
      screen reports and identified 418 patients potentially eligible for LCS. Over the
      next 7 months, we enrolled a total of 110 patients. Fifty-eight (53%) were
      identified from the tobacco screen, 32 (29%) were self-referred, and 20 (18%)
      were physician referrals. Three stage I lung cancers were detected and treated.
      The tobacco screen was easily implemented by clinic staff and took a median time
      of 2 minutes to enter for current and former smokers. Lack of response to
      attempts at telephone contact and objection to paying out-of-pocket costs were
      the most common reasons for failing to screen eligible patients. CONCLUSIONS: Use
      of augmented meaningful use criteria containing detailed tobacco exposure history
      is feasible and allows for identification of patients eligible for LCS in a
      medical center. Barriers to LCS include lack of insurance coverage and lack of
      systematic referral of patients at high risk.

PMID- 25063302
TI  - Discovery of the beta-barrel-type RNA methyltransferase responsible for N6
      methylation of N6-threonylcarbamoyladenosine in tRNAs.
AB  - Methylation is a versatile reaction involved in the synthesis and modification of
      biologically active molecules, including RNAs. N(6)-methyl-threonylcarbamoyl
      adenosine (m(6)t(6)A) is a post-transcriptional modification found at position 37
      of tRNAs from bacteria, insect, plants, and mammals. Here, we report that in
      Escherichia coli, yaeB (renamed as trmO) encodes a tRNA methyltransferase
      responsible for the N(6)-methyl group of m(6)t(6)A in tRNA(Thr) specific for ACY
      codons. TrmO has a unique single-sheeted beta-barrel structure and does not
      belong to any known classes of methyltransferases. Recombinant TrmO employs S
      adenosyl-L-methionine (AdoMet) as a methyl donor to methylate t(6)A to form
      m(6)t(6)A in tRNA(Thr). Therefore, TrmO/YaeB represents a novel category of
      AdoMet-dependent methyltransferase (Class VIII). In a DeltatrmO strain, m(6)t(6)A
      was converted to cyclic t(6)A (ct(6)A), suggesting that t(6)A is a common
      precursor for both m(6)t(6)A and ct(6)A. Furthermore, N(6)-methylation of t(6)A
      enhanced the attenuation activity of the thr operon, suggesting that TrmO ensures
      efficient decoding of ACY. We also identified a human homolog, TRMO, indicating
      that m(6)t(6)A plays a general role in fine-tuning of decoding in organisms from
      bacteria to mammals. 

PMID- 25063305
TI  - Clematichinenoside AR induces immunosuppression involving Treg cells in Peyer's
      patches of rats with adjuvant induced arthritis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Clematichinenoside AR (AR) has been defined as a
      major active ingredient of triterpenoid saponins extracted from Clematidis Radix
      et Rhizoma, which is a traditional Chinese herbal medicine that has long been
      used in the treatment of rheumatoid arthritis (RA). To further explore the
      mechanism of AR in the treatment of RA, we investigated whether its
      immunomodulatory effects are related to Treg-mediated suppression derived from
      Peyer's patches (PPs) in adjuvant induced arthritis (AIA) rat model. MATERIALS
      AND METHODS: AR (8, 16, 32 mg/kg) was orally administered daily from Day 18 to
      Day 31 after immunization. The effect of AR on AIA rats was evaluated by hind paw
      swelling and histopathological examination. Percentages of CD4(+)CD25(+)Foxp3(+)
      T regulatory cells were determined by flow cytometry. Levels of IL-10, TGF-beta1,
      IL-17A and TNF-alpha were measured by ELISA. Expressions of Foxp3 and RORgamma in
      synovium were detected using immunohistochemical analysis. RESULTS: AR treatment
      significantly reduced paw swelling of AIA rats, and histopathological analysis
      confirmed it could suppress severity of established arthritis. AR treatment
      upregulated the percentages of CD4(+)CD25(+)Foxp3(+) Treg cells among CD4+ T
      cells in PPs lymphocytes, and increased the levels of IL-10 and TGF-beta1
      secreted from ConA-activated PPs lymphocytes, whereas decreased the levels of IL
      17 A and TNF-alpha. Similar tendency of circulating CD4(+)CD25(+)Foxp3(+) Treg
      cells percentages and serum cytokine levels were observed. Moreover, AR decreased
      the expression levels of Foxp3 and RORgamma in joint synovial membrane.
      CONCLUSIONS: In conclusion, these results suggested AR has a potent protective
      effect on the progression of AIA, probably by augmenting CD4(+)CD25(+)Foxp3(+)
      Treg cells in PPs to induce immunosuppression, and modulating the balance between
      Treg cells and Th17 cells systemically. These findings may help to develop AR as
      a potent immunosuppressive agent for the treatment of RA.

PMID- 25063306
TI  - Effects of Xin-Ji-Er-Kang formula on 2K1C-induced hypertension and cardiovascular
      remodeling in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xin-Ji-Er-Kang (XJEK), a Chinese herbal formula,
      is effective against hypertension induced coronary heart disease, viral
      myocarditis and toxic myocarditis. In this study, the effect of XJEK on
      cardiovascular system was investigated. To test the hypothesis that Xin-Ji-Er
      Kang (XJEK) has an anti-hypertensive effect mediated through attenuation of
      cardiac remodeling, and amelioration of vascular endothelial dysfunction and
      oxidative stress. MATERIALS AND METHODS: Hypertension was induced in Wistar rats
      by 2 kidney 1 clip (2K1C) treatment. The hypertensive rats were then randomly
      assigned into four groups and treated as follows: group 1 (Sham-operated [Sh-Op]
      group received only drinking water), group 2 (induced hypertensive model+no
      treatment), and group 3 (induced hypertensive+a single daily oral dose of 24 g
      kg(-1) XJEK treatment) and group 4 (induced hypertensive+a single oral dose of 15
      mg kg(-1) Fosinopril treatment). The rats in all the defined groups were
      respectively treated for a period of 4 weeks. Cardiovascular parameter such as
      systolic blood pressure (SBP) was measured weekly by using tail-cuff apparatus;
      left ventricular systolic pressure (LVSP), left ventricular end-diastolic
      pressure (LVEDP) and the rate of the rise in left ventricular pressure (+/-dp/dt
      max) were measured by using a PowerLab 8/30 apparatus (AD Instruments, Australia)
      at the end of the 8th week; heart weight/body weight (HW/BW) was determined as an
      index of myocardial hypertrophy (MH). Hematoxylin and eosin (H&E) and Van Gieson
      (VG) stain were used to assess the cardio-histological changes. Colorimetric
      analysis was used to assay serum superoxide dismutase (SOD) activity,
      malondialdehyde (MDA), nitric oxide (NO), and hydroxyproline (Hyp) contents in
      cardiac tissue. Angiotensin II (Ang II) content in serum was assessed by
      radioimmunoassay; tetrahydrobiopterin (BH4) content in cardiac tissue, BNP and
      endothelial NOS (eNOS) in serum were determined by using ELISA, and the protein
      expressions of c-Jun NH2-terminal kinase (JNK), P-JNK, p38, P-p38, and NADPH
      oxidases-2 (Nox-2) were measured by western blot. RESULTS: XJEK therapy could
      impair the heart systolic and diastolic function, potently improve the heart
      weight index, inhibit the elevation of HW/BW ratio, and markedly ameliorate
      hemodynamic indices and vascular remodeling index. It has blunted the decrease of
      SOD, NO and the increase in MDA and Ang II serum contents, myocardial cross
      section area (CSA), collagen volume fraction (CVF) and perivascular
      circumferential collagen area (PVCA) compared to the hypertensive model group. It
      also reduced the serum content of Hyp while increased BH4 levels in cardiac
      tissue. In addition, the expressions of Nox-2, P-JNK and P-p38MAPK were all
      suppressed compared to the hypertensive model group. Moreover, treatment with
      XJEK improved endothelial dysfunction (ED) manifested by promoting eNOS
      activities and enhancing the NO activity in serum. CONCLUSION: The results of the
      present study show that XJEK attenuates 2K1C-induced hypertension in rats, which
      confirms our hypothesis that XJEK has an anti-hypertensive and cardiovascular
      remodeling effect via attenuation of cardiac remodeling and improvement of
      endothelial dysfunction and oxidative stress.

PMID- 25063307
TI  - Safety and efficacy of a multiphase dietetic protocol with meal replacements
      including a step with very low calorie diet.
AB  - To investigate safety, compliance, and efficacy, on weight loss and
      cardiovascular risk factors of a multiphasic dietary intervention based on meal
      replacements, including a period of very low calorie diet (VLCD) in a population
      of obese patients. Anthropometric parameters, blood tests (including insulin),
      dual-energy-X-ray absorptiometry (DXA), and questionnaires for the assessment of
      safety and compliance before and after (phase I) a 30-day VLCD, 700 kcal/day,
      normoproteic, 50 g/day carbohydrate, four meal replacements; (phase II) a 30-day
      low calorie diet (LCD), 820 kcal/day, three meal replacements plus a protein
      plate; (phase III) 60-day LCD, 1,100 kcal/day, two meal replacements plus two
      protein plates and reintroduction of small amounts of carbohydrates; (phase IV)
      60-day hypocaloric balanced diet (HBD), 1,200 kcal/day, one meal replacement, two
      protein plates and the reintroduction of carbohydrates. 24 patients (17 females,
      7 males, mean BMI 33.8+/-3.2 kg/m2, mean age 35.1+/-10.2 years) completed the
      study. The average weight loss was 15.4+/-6.7%, with a significant reduction of
      fat mass (from 32.8+/-4.7 to 26.1+/-6.3% p<0.05) and a relative increase of lean
      mass (from 61.9+/-4.8 to 67.1+/-5.9% p<0.05). An improvement of metabolic
      parameters and no variations of the liver and kidney functions were found. A high
      safety profile and an excellent dietary compliance were seen. The VLCD dietary
      program and the replacement dietary system described here is an effective, safe,
      and well-tolerated treatment for weight control.

PMID- 25063308
TI  - Pituitary apoplexy.
AB  - Pituitary apoplexy is a clinical syndrome of sudden headache and visual decline
      associated with acute hemorrhagic or ischemic change of an intrasellar mass, and
      comprises only a subset of hemorrhagic pituitary lesions. The most common
      presenting symptoms include headache, nausea, diminished visual acuity or visual
      field, ophthalmoplegia/paresis, and impaired mental status. Multiple risk factors
      have been reported, although the majority of cases have no identifiable
      precipitants. MRI is the most sensitive diagnostic modality, with specific
      imaging findings dependent on the timing post-hemorrhage. Early clinical
      suspicion is imperative to allow for corticosteroid replacement and hemodynamic
      stabilization when indicated. Transsphenoidal surgical decompression improves
      outcome in a majority of cases, although conservative management may be
      appropriate in select scenarios. 

PMID- 25063309
TI  - Day-night variations in thyroid stimulating hormone and its relation with
      clinical status and metabolic parameters in patients with cirrhosis of the liver.
AB  - To investigate day-night variations in thyroid stimulating hormone (TSH) and its
      relation with clinical status and metabolic parameters in patients with
      cirrhosis. Forty-one patients with negative thyroid antibodies and normal thyroid
      function tests who were diagnosed with cirrhosis were included. Thirty-five age-
      and gender-matched healthy subjects were included in control group.TSH, fT3, and
      fT4 levels, which were measured both in the morning and late evening. The
      difference between nocturnal TSH and morning TSH (DeltaTSH) were compared between
      groups. Relation between Child-Turcotte-Pugh, model for End-Stage Liver Disease
      (MELD) and MELD-Na scores and levels of thyroid hormones, DeltaTSH and serum
      sodium (Na) levels was investigated. Relation between DeltaTSH and clinical
      status and metabolic parameters was also evaluated. The mean morning fT3,
      nocturnal fT3, nocturnal TSH, and DeltaTSH levels were significantly lower,
      morning and nocturnal fT4 levels were higher in patients with cirrhosis (p<0.001,
      p<0.001, p=0.004, p<0.001, and p<0.001). As the ROC analysis, day-night variation
      was detected to be impaired in the event that difference between nocturnal TSH
      level and morning TSH level was lower than 1 uIU/mL in patients with cirrhosis
      with a sensitivity of 92.7% and specificity of 71.4% (p<0.001).A significant
      positive correlation was found between serum Na levels and fT3 in patients with
      cirrhosis (r=0.479, p=0.001), and a significant negative correlation was found
      between the severity of clinical status and low levels of fT3 in patients with
      cirrhosis (p<0.001).Nocturnal TSH increase does not occur in cases of cirrhosis
      without known thyroid disease and with normal thyroid function tests, which may
      be an early finding of impaired thyroid functions in patients with cirrhosis.

PMID- 25063310
TI  - Establishment of a novel, eco-friendly transgenic pig model using porcine
      pancreatic amylase promoter-driven fungal cellulase transgenes.
AB  - Competition between humans and livestock for cereal and legume grains makes it
      challenging to provide economical feeds to livestock animals. Recent increases in
      corn and soybean prices have had a significant impact on the cost of feed for pig
      producers. The utilization of byproducts and alternative ingredients in pig diets
      has the potential to reduce feed costs. Moreover, unlike ruminants, pigs have
      limited ability to utilize diets with high fiber content because they lack
      endogenous enzymes capable of breaking down nonstarch polysaccharides into simple
      sugars. Here, we investigated the feasibility of a transgenic strategy in which
      expression of the fungal cellulase transgene was driven by the porcine pancreatic
      amylase promoter in pigs. A 2,488 bp 5'-flanking region of the porcine pancreatic
      amylase gene was cloned by the genomic walking technique, and its structural
      features were characterized. Using GFP as a reporter, we found that this region
      contained promoter activity and had the potential to control heterologous gene
      expression. Transgenic pigs were generated by pronuclear microinjection. Founders
      and offspring were identified by PCR and Southern blot analyses. Cellulase mRNA
      and protein showed tissue-specific expression in the pancreas of F1 generation
      pigs. Cellulolytic enzyme activity was also identified in the pancreas of
      transgenic pigs. These results demonstrated the establishment of a tissue
      specific promoter of the porcine pancreatic amylase gene. Transgenic pigs
      expressing exogenous cellulase may represent a way to increase the intake of low
      cost, fiber-rich feeds. 

PMID- 25063311
TI  - Dendrimer-TPGS mixed micelles for enhanced solubility and cellular toxicity of
      taxanes.
AB  - Taxanes are the most effective, efficient and broad spectrum anticancer drugs for
      the treatment of various cancers. However, poor aqueous solubility is the major
      problem in their delivery at higher concentrations in cancer cells. In this
      research work, poor solubility of taxanes is addressed by preparing dendrimer and
      d-alpha-tocopherol polyethylene glycol succinate (TPGS) mixed micelles by taking
      into consideration the advantages of TPGS such as solubility enhancement and P
      glycoprotein inhibition. Dendrimer-TPGS mixed micelles were prepared by solvent
      casting method. Docetaxel (DTX) and paclitaxel (PTX) were chosen as model drugs
      representing the group of taxanes. Nanomicelles were characterized by DLS, FTIR,
      PXRD, in vitro drug release and hemolytic studies. Effects of pH and dendrimer to
      TPGS ratio on the solubility of taxanes were also studied. Solubility of DTX and
      PTX were increased by 20.36 and 34.95 folds, respectively, when formulated in
      dendrimer-TPGS mixed micelles. Drug release studies exhibited better release
      profile of encapsulated drug at acidic pH which is advantageous in enhanced
      intracellular drug release in cancer cells. Formulations were found to be
      biocompatible in hemolytic toxicity assay. Cytotoxicity studies revealed that
      anticancer activities of both drugs were enhanced after encapsulation in micelles
      against cancer cells while caused very low toxicity to normal cells. Thus,
      dendrimer-TPGS mixed micelles are promising alternate for delivery of poorly
      water-soluble drugs taxanes. 

PMID- 25063312
TI  - [Breastfeeding: health benefits for child and mother].
AB  - The prevalence of breastfeeding in France is one of the lowest in Europe: 65% of
      infants born in France in 2010 were breastfed when leaving the maternity ward.
      Exclusive breastfeeding allows normal growth until at least 6 months of age, and
      can be prolonged until the age of 2 years or more, provided that complementary
      feeding is started after 6 months. Breast milk contains hormones, growth factors,
      cytokines, immunocompetent cells, etc., and has many biological properties. The
      composition of breast milk is influenced by gestational and postnatal age, as
      well as by the moment of the feed. Breastfeeding is associated with slightly
      enhanced performance on tests of cognitive development. Exclusive breastfeeding
      for at least 3 months is associated with a lower incidence and severity of
      diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at
      least 4 months is associated with a lower incidence of allergic disease (asthma,
      atopic dermatitis) during the first 2 to 3 years of life in at-risk infants
      (infants with at least one first-degree relative presenting with allergy).
      Breastfeeding is also associated with a lower incidence of obesity during
      childhood and adolescence, as well as with a lower blood pressure and
      cholesterolemia in adulthood. However, no beneficial effect of breastfeeding on
      cardiovascular morbidity and mortality has been shown. Maternal infection with
      hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to
      HIV infection and galactosemia. A supplementation with vitamin D and K is
      necessary in the breastfed infant. Very few medications contraindicate
      breastfeeding. Premature babies can be breastfed and/or receive mother's milk
      and/or bank milk, provided they receive energy, protein and mineral supplements.
      Return to prepregnancy weight is earlier in breastfeeding mothers during the 6
      months following delivery. Breastfeeding is also associated with a decreased risk
      of breast and ovarian cancer in the premenopausal period, and of osteoporosis in
      the postmenopausal period. 

PMID- 25063313
TI  - Tunneling nanotubes: novel potentials for old players.

PMID- 25063314
TI  - Heme oxygenase-1 expression is associated with tumor aggressiveness and outcomes
      in patients with bladder cancer: a correlation with smoking intensity.
AB  - Heme oxygenase (HO)-1 is upregulated in malignancies and, in turn, regulates
      other cancer-related factors. Although HO-1 expression has been associated with
      cigarette smoking under various pathologic conditions, little is known about
      their association in patients with bladder cancer. HO-1 expression was assessed
      in 215 formalin-fixed bladder cancer specimens by immunohistochemistry.
      Microvessel density, lymph vessel density (LVD), proliferation index (PI), and
      expression of the vascular endothelial growth factor (VEGF)-A, -C, and -D,
      cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, and MMP-9 were
      investigated by similar methods. Multivariate analyses were performed to evaluate
      the pathologic role and predictive value of HO-1 expression. Our results
      demonstrated that HO-1 expression was positively associated with T stage, lymph
      node metastasis, and grade. HO-1 expression was also positively correlated with
      PI, LVD, and expression levels of VEGF-D, COX-2, MMP-2, and MMP-9 (P < 0.001). In
      addition, multivariate analyses showed that HO-1 expression positively correlated
      with smoking intensity. Positive HO-1 expression was a significant predictor of
      subsequent metastasis (P = 0.008) and poor cause-specific survival (P < 0.001).
      Similarly, multivariate analyses showed that HO-1 expression was a predictor of
      cause-specific survival (hazard ratio = 3.13, P = 0.013). In conclusion,
      pathologic changes of HO-1-related factors were dependent on smoking intensity.
      Smoking upregulated HO-1 expression, and HO-1 was associated with malignant
      behavior of bladder cancer. Cancer cell proliferation, lymphangiogenesis, and
      expression levels of VEGF-D, COX-2, and MMP-2 played important roles in these HO
      1-related effects. The clinical correlations of HO-1 were regulated by a complex
      mechanism that depended on smoking intensity.

PMID- 25063315
TI  - Analysis of clinical characteristics and differential diagnosis of the lung
      biopsy specimens in 99 adenocarcinoma cases and 111 squamous cell carcinoma
      cases: utility of an immunohistochemical panel containing CK5/6, CK34betaE12,
      p63, CK7 and TTF-1.
AB  - This study aimed at evaluating the utility of a panel of antibodies, consisting
      of cytokeratins (CK) 5/6, CK34betaE12, p63, thyroid transcription factor-1 (TTF
      1), and CK7 for distinguishing between squamous cell carcinoma (SCC) and
      adenocarcinomas (Ad), as well as their expression with clinicopathological
      parameters and prognosis in SCC and Ad. 111 SCC of small biopsy specimens and 99
      cases of Ad were stained by immunohistochemistry, among which 76 SCC and 64 Ad
      had complete follow-up data. Most of SCC displayed CK5/6 (91/99, 91.92%),
      CK34betaE12 (83/99, 83.84%), p63 (96/99, 96.97%), and most of Ad showed
      expression of CK7 (89/111, 80.18%) and TTF-1 (105/111, 94.59%). The combination
      of CK5/6/CK34betaE12/p63 seems to be useful for differentiating SCC from Ad with
      100% sensitivity and 97.30% specificity, and TTF-1 was a useful biomarker for Ad
      with 94.59% sensitivity and 100% specificity. There were differences between
      CK5/6, p63, and TTF-1 expression with tumor differentiation (p<0.05) in SCC or
      Ad. Univariate analysis indicated that patients with high TTF-1 expression
      predicted better prognosis in Ad patients. Multivariate analysis showed that TTF
      1 expression (HR=0.340, 95% CI 0.143-0.811, p=0.015) was a good independent
      predictor of Ad patient survival.

PMID- 25063316
TI  - Papillary cystadenoma of anterior one-third of the tongue.
AB  - Papillary cystadenoma is an unusual benign cystic neoplasm with cystic spaces of
      diverse sizes and intraluminal papillary projections histologically, which is
      commonly seen in the lips, cheek and palate. We report a case of papillary
      cystadenoma in a 40-year-old man on the anterior one-third of the tongue with
      classical histological features. The paper highlights the rarity of the site of
      occurrence with emphasis on differential diagnosis and the need for considering
      papillary cystadenoma when benign cystic lesions are encountered in the anterior
      one-third of the tongue. 

PMID- 25063317
TI  - Reversed halo sign in active pulmonary tuberculosis.

PMID- 25063318
TI  - Frontotemporal dementia: neuroanatomical correlates of an atypical presentation.
AB  - Frontotemporal dementia (FTD) is a heterogeneous group of disorders characterised
      by frontal and temporal lobes atrophy. Three different clinical subtypes are
      recognised: behavioural variant, progressive non-fluent aphasia and semantic
      dementia. Neuroanatomical associations in a diffuse neurodegenerative disease
      such as FTD should be interpreted carefully; however, each FTD subtype has
      provided a clinical model that has contributed immensely to our understanding of
      clinical/neuroanatomical relationships. This case report and recent studies
      suggest that neuroanatomical findings concerning face-processing mechanisms in
      FTD can identify the brain regions that are critical for face processing. As seen
      in this case, right fusiform gyrus atrophy seems to be implied in the aetiology
      of prosopagnosia. 

PMID- 25063319
TI  - Paediatric caecal volvulus with perforation and faecal peritonitis.

PMID- 25063320
TI  - Clinical management of paragangliomas.
AB  - Paragangliomas (PGLs) are rare vascular, neuroendocrine tumors of paraganglia,
      which are associated with either sympathetic tissue in adrenal (pheochromocytomas
      (PCCs)) and extraadrenal (sympathetic paraganglioma (sPGLs)) locations or
      parasympathetic tissue of the head and neck paragangliomas (HNPGLs). As HNPGLs
      are usually benign and most tumors grow slowly, a wait-and-scan policy is often
      advised. However, their location in the close proximity to cranial nerves and
      vasculature may result in considerable morbidity due to compression or
      infiltration of the adjacent structures, necessitating balanced decisions between
      a wait-and-see policy and active treatment. The main treatment options for HNPGL
      are surgery and radiotherapy. In contrast to HNPGLs, the majority of sPGL/PCCs
      produces catecholamines, in advanced cases resulting in typical symptoms and
      signs such as palpitations, headache, diaphoresis, and hypertension. The state-of
      the-art diagnosis and localization of sPGL/PCCs are based on measurement of
      plasma and/or 24-h urinary excretion of (fractionated) metanephrines and
      methoxytyramine (MT). sPGL/PCCs can subsequently be localized by anatomical
      (computed tomography and/or magnetic resonance imaging) and functional imaging
      studies (123I-metaiodobenzylguanidine-scintigraphy, 111In-pentetreotide
      scintigraphy, or positron emission tomography with radiolabeled dopamine or
      dihydroxyphenylalanine). Although most PGL/PCCs are benign, factors such as
      genetic background, tumor size, tumor location, and high MT levels are associated
      with higher rates of metastatic disease. Surgery is the only curative treatment.
      Treatment options for patients with metastatic disease are limited. PGL/PCCs have
      a strong genetic background, with at least one-third of all cases linked with
      germline mutations in 11 susceptibility genes. As genetic testing becomes more
      widely available, the diagnosis of PGL/PCCs will be made earlier due to routine
      screening of at-risk patients. Early detection of a familial PGL allows early
      detection of potentially malignant PGLs and early surgical treatment, reducing
      the complication rates of this operation.

PMID- 25063321
TI  - The genome and occlusion bodies of marine Penaeus monodon nudivirus (PmNV, also
      known as MBV and PemoNPV) suggest that it should be assigned to a new nudivirus
      genus that is distinct from the terrestrial nudiviruses.
AB  - BACKGROUND: Penaeus monodon nudivirus (PmNV) is the causative agent of spherical
      baculovirosis in shrimp (Penaeus monodon). This disease causes significant
      mortalities at the larval stage and early postlarval (PL) stage and may suppress
      growth and reduce survival and production in aquaculture. The nomenclature and
      classification status of PmNV has been changed several times due to morphological
      observation and phylogenetic analysis of its partial genome sequence. In this
      study, we therefore completed the genome sequence and constructed phylogenetic
      trees to clarify PmNV's taxonomic position. To better understand the
      characteristics of the occlusion bodies formed by this marine occluded virus, we
      also compared the chemical properties of the polyhedrin produced by PmNV and the
      baculovirus AcMNPV (Autographa californica nucleopolyhedrovirus). RESULTS: We
      used next generation sequencing and traditional PCR methods to obtain the
      complete PmNV genome sequence of 119,638 bp encoding 115 putative ORFs.
      Phylogenetic tree analysis showed that several PmNV genes and sequences clustered
      with the non-occluded nudiviruses and not with the baculoviruses. We also
      investigated the characteristics of PmNV polyhedrin, which is a functionally
      important protein and the major component of the viral OBs (occlusion bodies). We
      found that both recombinant PmNV polyhedrin and wild-type PmNV OBs were sensitive
      to acid conditions, but unlike the baculoviral OBs, they were not susceptible to
      alkali treatment. CONCLUSIONS: From the viral genome features and phylogenetic
      analysis we conclude that PmNV is not a baculovirus, and that it should be
      assigned to the proposed Nudiviridae family with the other nudiviruses, but into
      a distinct new genus (Gammanudivirus).

PMID- 25063322
TI  - Agrobacterium-mediated high-frequency transformation of an elite commercial maize
      (Zea mays L.) inbred line.
AB  - KEY MESSAGE: An improved Agrobacterium -mediated transformation protocol is
      described for a recalcitrant commercial maize elite inbred with optimized media
      modifications and AGL1. These improvements can be applied to other commercial
      inbreds. This study describes a significantly improved Agrobacterium-mediated
      transformation protocol in a recalcitrant commercial maize elite inbred, PHR03,
      using optimal co-cultivation, resting and selection media. The use of green
      regenerative tissue medium components, high copper and 6-benzylaminopurine, in
      resting and selection media dramatically increased the transformation frequency.
      The use of glucose in resting medium further increased transformation frequency
      by improving the tissue induction rate, tissue survival and tissue proliferation
      from immature embryos. Consequently, an optimal combination of glucose, copper
      and cytokinin in the co-cultivation, resting and selection media resulted in
      significant improvement from 2.6 % up to tenfold at the T0 plant level using
      Agrobacterium strain LBA4404 in transformation of PHR03. Furthermore, we
      evaluated four different Agrobacterium strains, LBA4404, AGL1, EHA105, and GV3101
      for transformation frequency and event quality. AGL1 had the highest
      transformation frequency with up to 57.1 % at the T0 plant level. However, AGL1
      resulted in lower quality events (defined as single copy for transgenes without
      Agrobacterium T-DNA backbone) when compared to LBA4404 (30.1 vs 25.6 %). We
      propose that these improvements can be applied to other recalcitrant commercial
      maize inbreds.

PMID- 25063323
TI  - Overexpression of Camellia sinensis H1 histone gene confers abiotic stress
      tolerance in transgenic tobacco.
AB  - KEY MESSAGE: Overexpression of CsHis in tobacco promoted chromatin condensation,
      but did not affect the phenotype. It also conferred tolerance to low-temperature,
      high-salinity, ABA, drought and oxidative stress in transgenic tobacco. H1
      histone, as a major structural protein of higher-order chromatin, is associated
      with stress responses in plants. Here, we describe the functions of the Camellia
      sinensis H1 Histone gene (CsHis) to illustrate its roles in plant responses to
      stresses. Subcellular localization and prokaryotic expression assays showed that
      the CsHis protein is localized in the nucleus, and its molecular size is
      approximately 22.5 kD. The expression levels of CsHis in C. sinensis leaves under
      various conditions were investigated by qRT-PCR, and the results indicated that
      CsHis was strongly induced by various abiotic stresses such as low-temperature,
      high-salinity, ABA, drought and oxidative stress. Overexpression of CsHis in
      tobacco (Nicotiana tabacum) promoted chromatin condensation, while there were
      almost no changes in the growth and development of transgenic tobacco plants.
      Phylogenetic analysis showed that CsHis belongs to the H1C and H1D variants of H1
      histones, which are stress-induced variants and not the key variants required for
      growth and development. Stress tolerance analysis indicated that the transgenic
      tobacco plants exhibited higher tolerance than the WT plants upon exposure to
      various abiotic stresses; the transgenic plants displayed reduced wilting and
      senescence and exhibited greater net photosynthetic rate (Pn), stomatal
      conductance (Gs) and maximal photochemical efficiency (Fv/Fm) values. All the
      above results suggest that CsHis is a stress-induced gene and that its
      overexpression improves the tolerance to various abiotic stresses in the
      transgenic tobacco plants, possibly through the maintenance of photosynthetic
      efficiency.

PMID- 25063324
TI  - The abiotic stress-responsive NAC-type transcription factor SlNAC4 regulates salt
      and drought tolerance and stress-related genes in tomato (Solanum lycopersicum).
AB  - KEY MESSAGE: SlNAC4 functions as a stress-responsive transcription factor and
      might be useful for crop salt and drought tolerance improvement. Abiotic
      stresses, especially salinity and drought, are major factors that significantly
      limit crop growth and productivity. Plant-specific NAC transcription factors play
      crucial roles in various stress responses. However, to date only little
      information regarding stress-related NAC genes is available in tomato.
      Previously, we reported that tomato SlNAC4-SlNAC10 genes are involved in response
      of various abiotic stresses. Expression analysis revealed that SlNAC4 was also
      induced significantly by MeJA, but not by ABA. To further unravel the function of
      SlNAC4 in response to abiotic stress, we investigated the effects of salt and
      drought stress on wild-type and SlNAC4-RNAi transgenic tomato plants. The results
      demonstrated that the root and shoot growth of RNAi plants was more inhibited by
      salt stress than that of wild-type at post-germination stage. The leaf salt assay
      also showed less tolerance in transgenic plants by retaining lower chlorophyll
      content compared with wild-type plants. In addition, transgenic plants became
      less tolerant to salt and drought stress in soil, which were demonstrated by
      lower levels of water and chlorophyll contents, and higher water loss rate in
      their leaves as compared to wild-type plants under stressed conditions. Notably,
      the expressions of multiple stress-related genes were downregulated in SlNAC4
      RNAi plants under both control and salt-stressed conditions. Collectively, these
      results highlight the important role of SlNAC4 functions as a stress-responsive
      transcription factor in positive modulation of abiotic stress tolerance through
      an ABA-independent signaling networks and possibly in response to biotic stress,
      and may hold promising applications in the engineering of salt- and drought
      tolerant tomato.

PMID- 25063325
TI  - RE: The Diesel Exhaust in Miners Study (DEMS): a nested case-control study of
      lung cancer and diesel exhaust.

PMID- 25063327
TI  - Eugenics, Heredity, and Huntington's Disease: A Brief Historical Perspective.

PMID- 25063328
TI  - New Perspectives on the Neuropathology in Huntington's Disease in the Human Brain
      and its Relation to Symptom Variation.
AB  - We review recent investigations regarding the relationship between selective
      neurodegeneration in the human brain and the variability in symptom profiles in
      Huntington's disease. Huntington's disease is a genetic neurodegenerative
      disorder caused by an expanded CAG repeat in exon 1 of the Huntingtin gene on
      chromosome 4, encoding a protein called huntingtin. The huntingtin protein is
      expressed ubiquitously in somatic tissue, however, the major pathology affects
      the brain with profound degeneration in the striatum and the cerebral cortex.
      Despite the disease being caused by a single gene, there is a major variability
      in the neuropathology, as well as major heterogeneity in the symptom profiles
      observed in Huntington's disease patients. The symptoms may vary throughout the
      disease course and present as varying degrees of movement disorder, cognitive
      decline, and mood and behavioral changes. To determine whether there is an
      anatomical basis underlying symptom variation, recent studies on the post-mortem
      human brain have shown a relationship between the variable degeneration in the
      forebrain and the variable symptom profile. In this review, we will summarize the
      progress relating cell loss in the striatum and cerebral cortex to symptom
      profile in Huntington's disease. 

PMID- 25063326
TI  - Role of BRAFV600E in the first preclinical model of multifocal infiltrating
      myopericytoma development and microenvironment.
AB  - Myopericytoma (MPC) is a rare tumor with perivascular proliferation of
      pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally
      aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of
      MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin;
      3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of
      BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and
      primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic
      differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)
      positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in
      vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib
      disrupted angiogenic and metabolic properties (~3-fold decrease) with down
      regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and
      ECM-associated long non-coding RNA (LincRNA) expression, with no effects in
      BRAF(WT)-pericytes. Vemurafenib also inhibited (~3-fold decrease) cell viability
      in vitro and in BRAF(WT/V600E)-positive thyroid MPC patient-derived xenograft
      (PDX) mice (n = 5 mice per group). We established the first BRAF(WT/V600E)
      dependent thyroid MPC cell culture. Our findings identify BRAF(WT/V600E) as a
      novel genetic aberration in MPC pathogenesis and MPC-associated biomarkers and
      imply that anti-BRAF(V600E) agents may be useful adjuvant therapy in
      BRAF(WT/V600E)-MPC patients. Patients with BRAF(WT/V600E)-MPC should be closely
      followed because of the risk for multifocality/recurrence. 

PMID- 25063329
TI  - Cognitive Dysfunction in Huntington's Disease: Humans, Mouse Models and Molecular
      Mechanisms.
AB  - Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative
      disorder due to an expanded CAG/polyglutamine repeat in the coding region of the
      huntingtin (htt) gene that causes the preferential degeneration of striatal
      neurons. Although HD is classically considered a motor disorder, cognitive
      decline manifests even before the appearance of motor symptoms, and reflects the
      impairment of additional neuronal populations, such as cortical and hippocampal
      neurons, in the presence of mutant htt (mhtt). Studies on cognitive dysfunction
      in HD patients have focused on the cortico-striatal pathway. Here we will
      describe that HD patients and mouse models share many cognitive defects.
      Alterations in hippocampal synaptic plasticity and function found in HD mouse
      models highlight that changes in the functioning of the hippocampal formation
      contribute to cognitive dysfunction in humans. The similarity between the
      cognitive dysfunction in HD patients and mouse models has helped to understand
      better how cognitive dysfunction takes place. Moreover, it validates the use of
      HD mice to study the molecular mechanisms involved in HD cognitive decline.
      Several studies in HD mouse models indicate that altered synaptic
      composition/function, deficient neurotrophic support, kinase/phosphatase
      imbalance, and transcription dysregulation play an important role in cognitive
      impairment. This knowledge opens the possibility of identifying relevant
      therapeutic targets to fight cognitive decline in HD. The finding that in HD many
      mechanisms are similarly altered in hippocampal and striatal neurons suggests the
      possibility of a common therapeutic strategy to ameliorate both cognitive and
      motor dysfunction. 

PMID- 25063330
TI  - Practice, progress and future directions for physical therapies in Huntingtons
      disease.
AB  - Physical therapies and exercise may have potential as a disease modifying agent
      in Huntington's disease (HD) and in recent years, there have been several small
      scale feasibility studies that have shown benefit as a result of physical
      interventions. When evaluating complex physical interventions, a phased approach
      using mixed methodology designs that report specific intervention components,
      adherence, acceptability, adverse events and defined intervention protocols is
      important for replication and planning of future trials and to ensure potential
      for implementation in clinical practice. A narrative review of the available
      literature related to physical activity, physical therapy and exercise in people
      with HD was performed using a population, intervention, comparison and outcome
      (PICO) approach. Eight studies met specific inclusion criteria and were reviewed
      in terms of their systematic conduct and reporting standards. All of the studies
      (n = 8) provided details of intervention including location and duration. The
      majority of interventions included balance training activities in combination
      with other complex activities of daily living that required therapist
      supervision. Two of the interventions were home based, the remainder were
      facility or hospital based. None of the studies reported adverse events whilst
      only 3/8 reported adherence rates which were ranging from 60-80%. In general,
      limited detail was provided on the specific individual components of the
      interventions. This review of primary publications and conference proceedings,
      suggests that researchers working in the field need to focus on clearer reporting
      of intervention protocols so as to generate a clearer understanding of the impact
      of exercise and physical therapies on the symptoms of HD, as well as any
      potential synergistic role alongside the impending disease-modifying
      interventions. 

PMID- 25063331
TI  - Home or Residential Care? The Role of Behavioral and Psychosocial Factors in
      Determining Discharge Outcomes for Inpatients with Huntington's Disease.
AB  - BACKGROUND: The progressive nature of Huntington's disease (HD) means that
      families often struggle to cope with increasing care needs of their affected
      family member. As a result, individuals with HD are likely to be at risk of
      hospitalization and subsequent early placement into residential care facilities.
      OBJECTIVE: To explore which factors were associated with early residential care
      placement in a group of hospitalized patients with HD. METHODS: A retrospective,
      systematic medical file audit of a neurological inpatient unit was conducted.
      Fifty-nine patients with HD were admitted from the community between January 2008
      and December 2011; of these, 31 patients were discharged home while 28 patients
      required discharge to a residential care facility. These two groups were compared
      on a range of demographic, clinical and psychosocial variables identified as
      precipitating the hospital admission. Group comparisons were performed using t
      tests and chi-square tests with Bonferroni correction for multiple comparisons.
      RESULTS: A higher proportion of men were placed in residential care than were
      able to return home (p = 0.045); and the group placed in residential care had
      longer inpatient hospital stays (p < 0.001). Groups did not differ in age,
      medications or disease duration. We found that psychosocial difficulties (p <
      0.001) and behavioral problems (p = 0.001), but not physical, cognitive, or
      psychiatric factors, significantly differentiated the groups. CONCLUSIONS:
      Patients with HD discharged to residential care were more likely to have
      psychosocial and behavioral problems, and lengthy hospital stays. These findings
      indicate the need for community-based psychosocial and behavior management
      interventions aimed at preventing residential care admissions for persons with
      HD.

PMID- 25063332
TI  - PBT2 Reduces Toxicity in a C. elegans Model of polyQ Aggregation and Extends
      Lifespan, Reduces Striatal Atrophy and Improves Motor Performance in the R6/2
      Mouse Model of Huntington's Disease.
AB  - BACKGROUND: There is evidence that interaction with biologically important
      metals, particularly copper and iron, contributes to the pathological aggregation
      and toxicity of the mutant huntingtin protein in HD. PBT2 is a novel 8
      hydroxyquinoline drug in clinical trials for AD and HD which restores metal
      homeostasis and has demonstrated neuroprotective and cognitive benefits in animal
      models of AD and in a Phase IIa clinical trial in AD patients. OBJECTIVES: We
      assessed efficacy of PBT2 to improve function in nematode and mouse models of HD.
      METHODS: We assessed the effects of PBT2 on motility in a strain of C. elegans
      engineered to overexpress an extended polyglutamine tract. We then assessed the
      effects of daily oral administration of PBT2 on the R6/2 mouse a vertebrate model
      of HD. Behavioural measures (Rotarod performance, clasping latency and duration)
      and measures of overall health (body weight, lifespan) were assessed throughout
      the study. At conclusion brains were evaluated for weight and lateral ventricle
      area. RESULTS: PBT2 significantly decreased paralysis caused by overexpression of
      an extended polyglutamine tract in a C. elegans. R6/2 mice treated with PBT2
      showed significantly better performance in the Rotarod task and significantly
      decreased duration of clasping than control animals. Mean body weight and brain
      weight in the PBT2 treatment group were significantly higher than the control
      cohort and median lifespan was prolonged by 26%. Mean lateral ventricle area in
      the PBT2-treated group was 46% smaller than in the control group. CONCLUSIONS:
      Treatment with PBT2 may be beneficial as a disease modifying therapy for HD.

PMID- 25063333
TI  - Caspase-6-Resistant Mutant Huntingtin Does not Rescue the Toxic Effects of
      Caspase-Cleavable Mutant Huntingtin in vivo.
AB  - BACKGROUND: The amelioration of behavioral and neuropathological deficits in mice
      expressing caspase-6-resistant (C6R) mutant huntingtin (mhtt), despite the
      presence of an expanded polyglutamine tract, highlights proteolysis of htt at the
      586aa caspase-6 (casp6) site may be an important mechanism in the pathogenesis of
      Huntington disease (HD). One possible explanation of these effects is that C6R
      mhtt could act as a dominant negative on mhtt. OBJECTIVE AND METHODS: To
      determine if the neuroprotective effect observed in the C6R mice is due to
      dominant negative effects, we crossed the C6R mice to the YAC128 HD mouse model
      to generate mice expressing both caspase-cleavable and C6R mhtt (YAC/C6R)
      concurrently and assessed previously defined behavioral and neuropathological
      endpoints. RESULTS: Our results demonstrate that YAC/C6R animals exhibit similar
      motor abnormalities and learning deficits as the YAC128 mice. Neuropathological
      analysis reveals a significant decrease in brain weight and striatal volume in
      the YAC/C6R mice comparable to the YAC128 mice. In contrast, and similar to
      previous findings, C6R mice demonstrate preserved brain weight and striatal
      volume. As expected, body weight is significantly increased in the YAC/C6R mice
      due to the increased levels of htt. CONCLUSIONS: The results of this study
      suggest that the lack of an HD phenotype in the C6R mice is most likely due to
      the absence of cleavage of htt and not due to suppression of expression of mhtt.

PMID- 25063334
TI  - Antidepressant-Like Effect of the Norepinephrine-Dopamine Reuptake Inhibitor
      Bupropion in a Mouse Model of Huntington's Disease with Dopaminergic Dysfunction.
AB  - BACKGROUND: The pre-motor stages of Huntington's disease (HD) are commonly
      associated with psychiatric manifestations including depression. Recent clinical
      data indicate that dopaminergic dysfunction is common in both symptomatic and pre
      manifest HD gene carriers. There is also increasing evidence implicating
      catecholamine dysfunction in the pathophysiology of depression. OBJECTIVE: In
      this study, we aimed to functionally investigate the dopaminergic system in the
      R6/1 mouse model of HD prior to onset of motor symptoms. METHODS: We assessed the
      effects of acute administration of bupropion (a dopamine-norepinephrine reuptake
      inhibitor) on spontaneous locomotor activity and depression-like behaviour (using
      the forced-swim test). RESULTS: Here we show that the bupropion-induced increased
      locomotor activity found in wild-type animals was no longer observed in HD mice.
      We also found that acute administration with bupropion rescued depressive-like
      behaviours in HD animals, possibly through dopamine D2/D3 receptor mechanisms.
      CONCLUSION: Our present data are the first in vivo evidence of an impaired
      dopamine D1 receptor-dependent function in pre-motor symptomatic R6/1 HD mice.
      Moreover, our findings suggest clinical potential for bupropion to alleviate
      depressive symptoms in HD.

PMID- 25063335
TI  - Direct Visualisation of Abnormal Dendritic Spine Morphology in the Hippocampus of
      the R6/2 Transgenic Mouse Model of Huntington's Disease.
AB  - BACKGROUND: Spatial learning deficits are observed in R6/2 mice, a transgenic
      mouse model of Huntington's Disease (HD). Spatial learning is a hippocampal
      dependent process, and impairment of memory is thought to be due, at least in
      part, to structural changes such as loss of dendritic spines. OBJECTIVE: To
      analyse dendritic spines in the hippocampus of R6/2 mice to determine if there
      are changes that correlate with the hippocampal dysfunction observed in these
      mice. METHODS: A double transgenic cross between R6/2 mice and a reporter line
      (YFP-H) of mice that express yellow fluorescent protein (YFP) in a subset of
      their neurons was used. This allowed us to visualise dendritic spines in the
      brains of R6/2 mice directly. RESULTS: Clear differences were seen in the
      distribution of YFP in the hippocampal formation of wild-type (WT)-YFP-H and R6/2
      YFP-H mice, particularly in the CA1 region. We quantified dendritic spine density
      and dendritic spine length in the apical dendrites of the CA1 hippocampal
      neurons. A significant reduction in dendritic spine density, and a concomitant
      increase in dendritic spine length was observed in R6/2-YFP-H mice compared to WT
      YFP-H mice. CONCLUSION: The R6/2-YFP-H mouse is a useful tool for directly
      visualising dendritic spines in the brain of a Huntington's disease mouse model.
      The changes we observed in dendritic spine density and length in the hippocampus
      might contribute to the synaptic plasticity deficits and behavioural alteration
      of impaired spatial learning seen in R6/2 mice.

PMID- 25063336
TI  - Implementation and evaluation of an Asbru-based decision support system for
      adjuvant treatment in breast cancer.
AB  - The domain of cancer treatment is a promising field for the implementation and
      evaluation of a protocol-based clinical decision support system, because of the
      algorithmic nature of treatment recommendations. However, many factors can limit
      such systems' potential to support the decision of clinicians: technical
      challenges related to the interoperability with existing electronic patient
      records and clinical challenges related to the inherent complexity of the
      decisions, often collectively taken by panels of different specialists. In this
      paper, we evaluate the performances of an Asbru-based decision support system
      implementing treatment protocols for breast cancer, which accesses data from an
      oncological electronic patient record. Focusing on the decision on the adjuvant
      pharmaceutical treatment for patients affected by early invasive breast cancer,
      we evaluate the matching of the system's recommendations with those issued by the
      multidisciplinary panel held weekly in a hospital. 

PMID- 25063337
TI  - Structural features of peptoid-peptide hybrids in lipid-water interfaces.
AB  - The inclusion of peptoid monomers into antimicrobial peptides (AMPs) increases
      their proteolytic resistance, but introduces conformational flexibility (reduced
      hydrogen bonding ability and cis/trans isomerism). We here use NMR spectroscopy
      to answer how the insertion of a peptoid monomer influences the structure of a
      regular alpha-helical AMP upon interaction with a dodecyl phosphocholine (DPC)
      micelle. Insertion of [(2-methylpropyl)amino]acetic acid in maculatin-G15 shows
      that the structural change and conformational flexibility depends on the site of
      insertion. This is governed by the micelle interaction of the amphipathic helices
      flanking the peptoid monomer and the side chain properties of the peptoid and its
      preceding residue. 

PMID- 25063338
TI  - Screening-based discovery of Aspergillus fumigatus plant-type chitinase
      inhibitors.
AB  - A limited therapeutic arsenal against increasing clinical disease due to
      Aspergillus spp. necessitates urgent characterisation of new antifungal targets.
      Here we describe the discovery of novel, low micromolar chemical inhibitors of
      Aspergillus fumigatus family 18 plant-type chitinase A1 (AfChiA1) by high
      throughput screening (HTS). Analysis of the binding mode by X-ray crystallography
      confirmed competitive inhibition and kinetic studies revealed two compounds with
      selectivity towards fungal plant-type chitinases. These inhibitors provide new
      chemical tools to probe the effects of chitinase inhibition on A. fumigatus
      growth and virulence, presenting attractive starting points for the development
      of further potent drug-like molecules. 

PMID- 25063339
TI  - Can the use of medical muds cause genotoxicity in eukaryotic cells? A trial using
      comet assay.
AB  - Despite the lack of knowledge of their exact effects, peloids (natural muds) are
      widely applied in clinical treatment and prevention of different diseases,
      especially in rheumatic and gynecological disorders or skin diseases. Primarily
      we have information on their inorganic components, but only limited data are
      available on the organic components and nothing on their mechanism of chemical
      action. The objective of the present study was to detect the DNA-damaging effects
      (possible genotoxic effect) of peloid samples using the single-cell comet assay
      on Long Evans rat lymphocytes, human lymphocytes, and Eisenia fetida
      coelomocytes. Rat and human lymphocytes were exposed to the in toto peloid
      samples, in vitro. The Eisenia cells were extracted from the coelom of animals
      kept in the intact peloid sample. An indicator derived from the DNA fluorescence
      intensity was used in the statistical evaluation. The predominantly organic
      (Heviz) sample showed a significant alteration from the negative control in
      several cases, while the inorganic (Kolop) applied did not. A higher quantity of
      organic compounds may have an important role in the emergence of DNA damage. The
      results revealed that medical muds have not only positive health effects but can
      also contain substances with potential human toxicity risk. Our research provides
      essential steps towards the creation of a toxicity profile and the possible safe
      use of peloids as medicinal therapy. 

PMID- 25063340
TI  - Inpatient allergy testing in patients with infective endocarditis: an un-met
      need?

PMID- 25063341
TI  - Acoustic emission source location in plates using wavelet analysis and cross time
      frequency spectrum.
AB  - In this study, the theories of wavelet transform and cross-time frequency
      spectrum (CTFS) are used to locate AE source with frequency-varying wave velocity
      in plate-type structures. A rectangular array of four sensors is installed on the
      plate. When an impact is generated by an artificial AE source such as Hsu-Nielsen
      method of pencil lead breaking (PLB) at any position of the plate, the AE signals
      will be detected by four sensors at different times. By wavelet packet
      decomposition, a packet of signals with frequency range of 0.125-0.25MHz is
      selected. The CTFS is calculated by the short-time Fourier transform of the cross
      correlation between considered packets captured by AE sensors. The time delay is
      calculated when the CTFS reaches the maximum value and the corresponding
      frequency is extracted per this maximum value. The resulting frequency is used to
      calculate the group velocity of wave velocity in combination with dispersive
      curve. The resulted locating error shows the high precision of proposed
      algorithm. 

PMID- 25063342
TI  - Use of a chronic model of articular cartilage and meniscal injury for the
      assessment of long-term effects after autologous mesenchymal stromal cell
      treatment in sheep.
AB  - Regenerative therapies using adult stem cells have attracted great interest in
      the recent years and offer a promising alternative to current surgical practices.
      In this report, we evaluated the safety and efficacy of an autologous cell-based
      treatment of osteoarthritis using mesenchymal stromal cells expanded from bone
      marrow aspirates that were administered intra-articularly. Ten 2-year old ewes
      were divided in two groups (for analysis at 6 and 12 months, respectively). Full
      thickness articular cartilage defects of approximately 60mm(2) were created
      arthroscopically in the medial femorotibial condyles and a meniscal tear in the
      anterior horn of the medial meniscus in the 20 hind legs. Intra-articular
      injection of 4 mL of either treatment (a suspension of cells) or control (same as
      treatment, without cells) were applied one month after generating a chronic
      condition similar to human pathology. Animals were monitored radiographically, by
      MRI and ultrasound scanning; and macroscopic and histological analyses were
      conducted at 6 and 12 months. Furthermore a full necropsy was performed at 12
      months post-treatment. The intra-articular injection of autologous MSC was safe,
      as judged by the lack of local or systemic adverse effects during the clinical
      follow-up and by a full necropsy performed at 12 months post-treatment. Evidence
      of regeneration of articular cartilage and meniscus was case-dependent but
      statistically significant improvement was found in specific macroscopic and
      histological parameters. Such parameters included colour, rigidity, cell
      distribution and hyaline quality of the refill tissue as well as the structure of
      subchondral bone.

PMID- 25063343
TI  - Higher staff costs likely to tip many NHS trusts into red.

PMID- 25063344
TI  - Adult ADHD and suicide.
AB  - While suicidal behaviour has been implicated in a plethora of psychiatric
      disorders including depression, psychoses and substance abuse, its association
      with adult ADHD is largely under-researched. Given that emotional instability and
      the high prevalence of comorbid conditions such as mood disorders and
      alcohol/drug dependence are typical for ADHD, the question of suicide risk must
      not be neglected in this patient group. A review of the current literature
      focusing on this issue provides strong evidence that ADHD patients are at a
      significant risk for experiencing suicidal ideations and committing suicide. For
      daily clinical practice, it is therefore essential to incorporate this aspect
      into the diagnostic and therapeutic process and to take preventive measures. 

PMID- 25063345
TI  - [Hallucinations and borderline personality disorder: a review].
AB  - INTRODUCTION: Hallucinations constitute understudied symptoms in borderline
      personality disorders (BPD), which can be observed in about 30% of the patients,
      essentially in the auditory modality. Most of these experiences are transitory,
      triggered by intermittent stressors, but chronicity remains a major cause of
      concern. In order to better circumscribe hallucinations in BPD, we summarized the
      literature on this particular phenomenon. METHODS: We conducted a review using
      Medline, Scopus and Google Scholar databases up to March 2013, using the
      following keywords combinations: "borderline personality disorder", "hallucinat*"
      and "psychotic symptoms". Papers were included in the review if they were
      published in an English or French language peer-reviewed journal; the study
      enrolled patients with BPD; and the diagnosis was made according to the
      Diagnostic and Statistical Manual (DSM) criteria. Fifteen studies published
      between 1985 and 2012, merging a total of 635 patients, were retained. RESULTS:
      The hallucinatory experiences observed in BPD appeared phenomenologically similar
      to those described in the schizophrenia spectrum in terms of vividness, duration,
      spatial localization, beliefs about malevolence or omnipotence. Conversely, the
      hallucinatory content appeared more negative and potentially more distressful.
      Crucially, this literature search also revealed that these symptoms have long
      been regarded as "pseudo-hallucinations" (or "hallucination-like symptoms"). This
      concept was judged of poor scientific validity, inducing stigma for BPD patients
      in that it casts doubt on the authenticity of these experiences while
      disqualifying the related distress. This situation points out that research
      should focus more on understanding hallucinations in BPD than questioning their
      existence. Interestingly, recent comorbidity studies reopened a 40-year debate on
      the potential links that may exist between BPD and psychosis. Initially
      considered as a para-psychotic disorder, BPD was effectively redefined as an
      independent category by Otto F. Kernberg, leading to the DSM-III definition,
      excluding any psychotic symptom. However, hallucinations per se remain
      insufficient to diagnose schizophrenia, while comorbid substance use disorders as
      well as mood disorders, cannot explain all the hallucination occurrences in BPD.
      By referring to the "psychotic-reactivity-to-stress" framework, we proposed to
      understand hallucinations in BPD in relation to a hyperactivity of the
      hypothalamic-pituitary-adrenal axis and of the dopaminergic system under stress.
      Childhood trauma may have a central role in such a model. The prevalence of
      childhood trauma is high in BPD but this factor was also evidenced strongly
      linked with hallucinations in non-clinical populations. Comparisons are finally
      made and discussed between hallucinations occurring in BPD and those observed in
      posttraumatic stress disorder, another frequent comorbid disorder. CONCLUSION:
      Almost a third of patients with BPD experiences hallucinations, and future
      studies will have to clarify the pathophysiology of this symptom, still poorly
      understood. Both the models of psychotic-reactivity-to-stress, as well as the
      role of childhood trauma in the context of a gene X environment interaction,
      appear to be promising cues for future research.

PMID- 25063346
TI  - Gene delivery in mouse auditory brainstem and hindbrain using in utero
      electroporation.
AB  - BACKGROUND: Manipulation of gene expression via recombinant viral vectors and
      creation of transgenic knock-out/in animals has revolutionized our understanding
      of genes that play critical roles during neuronal development and pathophysiology
      of neurological disorders. Recently, target-specific genetic manipulations are
      made possible to perform in combination with specific Cre-lines, albeit costly,
      labor-intensive and time consuming. Thus, alternative methods of gene
      manipulations to address important biological questions are highly desirable. In
      this study, we utilized in utero electroporation technique which involves
      efficient delivery of hindbrain-specific enhancer/promoter construct, Krox20 into
      the third ventricle of live mouse embryo to investigate green fluorescent protein
      (GFP) expression pattern in mouse auditory brainstem and other hindbrain neurons.
      RESULTS: We created a GFP/DNA construct containing a Krox20 B enhancer and beta
      globin promoter to drive GFP expression in the hindbrain via injection into the
      third ventricle of E12 to E13.5 mice. Electrical currents were applied directly
      to the embryonic hindbrain to allow DNA uptake into the cell. Confocal images
      were then acquired from fixed brain slices to analyze GFP expression in mouse
      whole brain at different postnatal stages (P6-P21). By using a cell-type specific
      enhancer as well as region specific injection and electroporation, robust GFP
      expression in the cerebellum and auditory brainstem but not in the forebrain was
      observed. GFP expression in calyx of Held terminals was more robust in <P15
      compared to >P15 mice. In contrast, GFP expression in MNTB neurons was more
      prevalent in >P15 compared to <P15. In regards to the relative expression of GFP
      versus the synaptic marker Vglut1, percentage fluorescence GFP intensity in the
      calyx was higher in P11 to P15 than P6 to P10 and P16 to P21 groups. CONCLUSIONS:
      Taken together, this technique would potentially allow hindbrain-specific genetic
      manipulations such as knock-down, knock-in and rescue experiments to unravel
      critical molecular substrates underpinning functional and morphological
      remodeling of synapses as well as understanding the pathophysiology of certain
      neurological disorders targeting not only the auditory brainstem but also other
      parts of hindbrain, most notably the cerebellum.

PMID- 25063347
TI  - Challenges in community-based research with Latino migrant farmworker children
      and families.

PMID- 25063348
TI  - Enabling trust in qualitative research with culturally diverse participants.

PMID- 25063349
TI  - Understanding internet sex-seeking behaviour and sexual risk among young men who
      have sex with men: evidences from a cross-sectional study.
AB  - OBJECTIVE: Internet sex-seeking is common among young men who have sex with men
      (MSM). However, research examining its association with risky sexual behaviour
      has produced mixed findings, possibly due to various operational definitions of
      internet sex-seeking which fail to account for its multi-dimensionality. This
      study purposed to: (1) examine if the way internet sex-seeking behaviour is
      operationalised influences its association with risky sexual behaviour
      (unprotected anal intercourse (UAI) and casual sex) and (2) determine the
      association of each operational definition with sexual risk. METHODS: We
      recruited 263 sexually-experienced young MSM (18-29 years) and operationalised
      internet sex-seeking behaviour in four ways: (i) ever used the internet to meet
      other men, (ii) currently own a profile on a website dedicated to meeting other
      men, (iii) ever physically met a man you initially met online and (iv) ever had
      sex with a man you met online. Using binomial regression, we examined the
      association of each operationalisation with UAI and casual sex. RESULTS: Only MSM
      who reported physically meeting a man they met online and those who ever had sex
      with a man they met online were more likely to report a history of UAI (p<0.05),
      while MSM who engaged in all forms of internet sex-seeking were more likely to
      engage in casual sex (p<0.05). However, the strength of these associations varied
      according to the mode of operationalisation. CONCLUSIONS: The way internet sex
      seeking is operationalised in research is differentially associated with sexual
      risk. Against this backdrop, the utility of these operational definitions in
      future research and inferences drawn from such research must be interpreted with
      caution. Findings have important implications for sexual health research and
      methodology, survey development, sexual health prevention interventions, and
      evaluating sexual risk among young MSM.

PMID- 25063350
TI  - Do the symptoms of language disorder align with treatment goals? An exploratory
      study of primary-grade students' IEPs.
AB  - Individual Education Plans (IEPs) are legal documents that guide the treatment of
      students with language disorder (LD). This exploratory study investigated the
      extent to which students' symptoms of LD align with goals on their IEPs. A total
      of 99 kindergarten and first-grade students receiving treatment for LD in the
      public schools participated. IEPs were collected and coded for each student and
      norm-referenced measures were used to assess students' grammar, vocabulary,
      listening comprehension, and literacy skills in the fall of the academic year.
      Results showed there to be alignment between students' symptoms and IEP goals
      only in the area of vocabulary, such that students who had an IEP goal for
      vocabulary had lower scores on a vocabulary assessment than those without a goal.
      In general, there is limited alignment between observed symptoms of LD and
      treated symptoms as identified on students' IEPs. The limited alignment found in
      this study suggests more investigation is needed to understand the extent to
      which IEP goals, as potential indicators of treatment foci, should map on to
      students' symptoms. LEARNING OUTCOMES: Readers will be able to: (1) explain the
      theoretical and practical relevance of treatment goals aligning to symptoms for
      children with language impairment; (2) identify three analytic methods used to
      investigate alignment between treatment goals and symptoms; and (3) describe the
      extent to which IEP goals align to children's symptoms in a sample of children
      receiving services in the public schools.

PMID- 25063351
TI  - Tumor necrosis factor beta NcoI polymorphism (rs909253) is associated with
      inflammatory and metabolic markers in acute ischemic stroke.
AB  - Polymorphisms in genes coding for pro-inflammatory molecules represent important
      factors for the pathogenesis and outcome of stroke. The aim of this study was to
      evaluate the relationship between the tumor necrosis factor beta (TNF-beta) NcoI
      (rs909253) polymorphism with inflammatory and metabolic markers in acute ischemic
      stroke. Ninety-three patients and 134 controls were included. The TNF-beta
      polymorphism was determined using PCR-RFLP with NcoI restriction enzyme. Stroke
      subtypes and neurological deficit score were evaluated. White blood cell counts,
      erythrocyte sedimentation rate (ESR), plasma levels of IL-6 and TNF-alpha, serum
      high sensitivity C-reactive Protein (hsCRP), serum lipid profile, plasma levels
      of glucose and insulin, and homeostatic model assessment of insulin resistance
      (HOMA-IR) were determined. Stroke patients presented higher white blood cell
      counts, hsCRP, ESR, glucose, insulin, and HOMA-IR, and lower HDL cholesterol than
      controls (p < 0.01). There was no difference in genotypic and allelic frequency
      of TNF-beta NcoI polymorphism among patients and controls (p > 0.05). However,
      stroke patients carrying the TNFB2/B2 genotype presented higher levels of TNF
      alpha, white blood cell counts, total cholesterol, LDL cholesterol, glucose,
      insulin, and HOMA-IR than those with other genotypes (p < 0.05). White blood
      cells, IL-6, hsCRP, and ESR were positively correlated with the neurological
      deficit of the patients (p < 0.05). Taken together, TNF-beta NcoI polymorphism,
      by itself, was not associated with increased susceptibility for stroke
      development. However, the homozygous genotype for the allele TNFB2 was associated
      with higher expression of classical inflammatory and metabolic markers of
      development and outcome of stroke than other genotypes. The identification of
      variant alleles might allow both better prediction of susceptibility for stroke
      as well the identification of novel stroke mechanisms that could be target to new
      therapeutic approaches. Stroke patients carrying the TNFB2 variant allele could
      have a beneficial effect with the anti-inflammatory therapies in the early
      inflammatory phase of stroke.

PMID- 25063352
TI  - Risk Factors for Self-reported Driving Under the Influence of Alcohol and/or
      Illicit Drugs Among Older Adults.
AB  - PURPOSE OF THE STUDY: Despite the increasing number of older adults who have a
      history of substance use, little research has been done on alcohol- and drug
      related driving safety among older drivers. This study (a) examined risk factors
      for older adults' driving under the influence of alcohol and/or drugs (DUI) and
      (b) discerned differences between those aged 50-64 and those aged 65+. DESIGN AND
      METHODS: Data came from the public use files of the 2008-2012 National Survey on
      Drug Use and Health for respondents aged 50+ (N = 29,634). Descriptive statistics
      were used to present sample characteristics by past year substance use and self
      reported DUI status for age groups 50-64 and 65+. Age group separate binary
      logistic regression analysis was used to identify risk factors for DUI. RESULTS:
      Of past-year substance users in the 50-64 and the 65+ age groups, 14.54% and
      6.19%, respectively, self-reported DUI. Higher frequency alcohol use, binge
      drinking, marijuana use, and major depressive episode significantly increased the
      odds of DUI in both age groups. Lifetime arrest history was a predictor in the
      65+ age group only. IMPLICATIONS: Research is needed to improve identification of
      older drivers at high risk of DUI. Driving safety assessments for older adults
      can incorporate screening for substance abuse and comorbid mental conditions to
      identify those at high DUI risk. Older adults who engage in risky substance use
      should be directed to appropriate services that address substance use and mental
      health problems concurrently.

PMID- 25063353
TI  - Do Higher Levels of Resilience Buffer the Deleterious Impact of Chronic Illness
      on Disability in Later Life?
AB  - PURPOSE OF THE STUDY: In examining the ability of resilience, or the ability to
      navigate adversity in a manner that protects well-being, to buffer the impact of
      chronic disease onset on disability in later life, the authors tested 2
      hypotheses: (a) People with greater levels of resilience will have lower levels
      of disability and (b) resilience will moderate the association between the onset
      of a new chronic condition and subsequent disability. DESIGN AND METHODS: This
      study used a sample of 10,753 Americans between the ages of 51 and 98, derived
      from 3 waves of the Health and Retirement Study (2006-2010). Ordinary least
      squares regression was used to estimate the impact of resilience on changes in
      disability (measured as difficulty with activities of daily living [ADLs] and
      instrumental activities of daily living [IADLs]) over a 2-year period using a
      simplified resilience score. RESULTS: Resilience protects against increases in
      ADL and IADL limitations that are often associated with aging. Resilience
      mitigates a considerable amount of the deleterious consequences related to the
      onset of chronic illness and subsequent disability. IMPLICATIONS: Our results
      support our hypotheses and are consistent with claims that high levels of
      resilience can protect against the negative impact of disability in later life.

PMID- 25063354
TI  - Central cyanosis on a psychiatric unit treated at the Salford Royal Hospital.
AB  - We describe a case of acquired methaemoglobinaemia due to frequent use of the
      'legal high' known as 'Pink Panthers'. This contains 5,6-Methylenedioxy-2
      aminoindane and 2-Aminoindane, both amphetamine analogues with the potential to
      cause methaemoglobinaemia. Furthermore, the most common 'cutting agent' for legal
      highs in the UK is benzocaine, also known to cause methaemoglobinaemia. Given the
      increasing prevalence of legal highs, particularly those containing added
      benzocaine, such presentations may become more common. Furthermore, in one case
      series, benzocaine gel used for toothache was the second most common reason for
      hospitalisation due to acquired methaemoglobinaemia after dapsone use. Indeed,
      the Federal Drug Agency has issued as public warning as to the risk of these
      products. We therefore think that clinicians and the public should be made more
      aware of the risk associated with such agents. 

PMID- 25063355
TI  - Characterization of reconstituted high-density lipoprotein particles formed by
      lipid interactions with human serum amyloid A.
AB  - The acute-phase human protein serum amyloid A (SAA) is enriched in high-density
      lipoprotein (HDL) in patients with inflammatory diseases. Compared with normal
      HDL containing apolipoprotein A-I, which is the principal protein component,
      characteristics of acute-phase HDL containing SAA remain largely undefined. In
      the present study, we examined the physicochemical properties of reconstituted
      HDL (rHDL) particles formed by lipid interactions with SAA. Fluorescence and
      circular dichroism measurements revealed that although SAA was unstructured at
      physiological temperature, alpha-helix formation was induced upon binding to
      phospholipid vesicles. SAA also formed rHDL particles by solubilizing
      phospholipid vesicles through mechanisms that are common to other exchangeable
      apolipoproteins. Dynamic light scattering and nondenaturing gradient gel
      electrophoresis analyses of rHDL after gel filtration revealed particle sizes of
      approximately 10nm, and a discoidal shape was verified by transmission electron
      microscopy. Thermal denaturation experiments indicated that SAA molecules in rHDL
      retained alpha-helical conformations at 37 degrees C, but were almost completely
      denatured around 60 degrees C. Furthermore, trypsin digestion experiments showed
      that lipid binding rendered SAA molecules resistant to protein degradation. In
      humans, three major SAA1 isoforms (SAA1.1, 1.3, and 1.5) are known. Although
      these isoforms have different amino acids at residues 52 and 57, no major
      differences in physicochemical properties between rHDL particles resulting from
      lipid interactions with SAA isoforms have been found. The present data provide
      useful insights into the effects of SAA enrichment on the physicochemical
      properties of HDL. 

PMID- 25063356
TI  - Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of
      non-antiretroviral therapeutics.
AB  - The growing recognition of the burden of neurologic disease associated with HIV
      infection in the last decade has led to renewed efforts to characterize the
      pathophysiology of the virus within the central nervous system (CNS). The concept
      of the AIDS-dementia complex is now better understood as a spectrum of HIV
      associated neurocognitive disorders (HAND), which range from asymptomatic disease
      to severe impairment. Recent work has shown that even optimally treated patients
      can experience not only persistent HAND, but also the development of new
      neurologic abnormalities despite viral suppression. This has thrown into question
      what the impact of antiretroviral therapy has been on the incidence and
      prevalence of neurocognitive dysfunction. In this context, the last few years
      have seen a concentrated effort to identify the effects that antiretroviral
      therapy has on the neurologic manifestations of HIV and to develop therapeutic
      modalities that might specifically alter the trajectory of HIV within the CNS. 

PMID- 25063357
TI  - Analysis of contributing factors associated to related patients safety incidents
      in Intensive Care Medicine.
AB  - OBJECTIVE: To explore contributing factors (CF) associated to related critical
      patients safety incidents. DESIGN: SYREC study pos hoc analysis. SETTING: A total
      of 79 Intensive Care Departments were involved. PATIENTS: The study sample
      consisted of 1.017 patients; 591 were affected by one or more incidents. MAIN
      VARIABLES: The CF were categorized according to a proposed model by the National
      Patient Safety Agency from United Kingdom that was modified. Type, class and
      severity of the incidents was analyzed. RESULTS: A total 2,965 CF were reported
      (1,729 were associated to near miss and 1,236 to adverse events). The CF group
      more frequently reported were related patients factors. Individual factors were
      reported more frequently in near miss and task related CF in adverse events. CF
      were reported in all classes of incidents. The majority of CF were reported in
      the incidents classified such as less serious, even thought CF patients factors
      were associated to serious incidents. Individual factors were considered like
      avoidable and patients factors as unavoidable. CONCLUSIONS: The CF group more
      frequently reported were patient factors and was associated to more severe and
      unavoidable incidents. By contrast, individual factors were associated to less
      severe and avoidable incidents. In general, CF most frequently reported were
      associated to near miss.

PMID- 25063358
TI  - Genetic information, non-discrimination, and privacy protections in genetic
      counseling practice.
AB  - The passage of the Genetic Information Non Discrimination Act (GINA) was hailed
      as a pivotal achievement that was expected to calm the fears of both patients and
      research participants about the potential misuse of genetic information. However,
      6 years later, patient and provider awareness of legal protections at both the
      federal and state level remains discouragingly low, thereby, limiting their
      potential effectiveness. The increasing demand for genetic testing will expand
      the number of individuals and families who could benefit from obtaining accurate
      information about the privacy and anti-discriminatory protections that GINA and
      other laws extend. In this paper we describe legal protections that are
      applicable to individuals seeking genetic counseling, review the literature on
      patient and provider fears of genetic discrimination and examine their awareness
      and understandings of existing laws, and summarize how genetic counselors
      currently discuss genetic discrimination. We then present three genetic
      counseling cases to illustrate issues of genetic discrimination and provide
      relevant information on applicable legal protections. Genetic counselors have an
      unprecedented opportunity, as well as the professional responsibility, to
      disseminate accurate knowledge about existing legal protections to their
      patients. They can strengthen their effectiveness in this role by achieving a
      greater knowledge of current protections including being able to identify
      specific steps that can help protect genetic information.

PMID- 25063359
TI  - N6-isopentenyladenosine affects cytotoxic activity and cytokines production by IL
      2 activated NK cells and exerts topical anti-inflammatory activity in mice.
AB  - N6-isopentenyladenosine (iPA) is a modified adenosine with an isopentenyl moiety
      derived from the mevalonate pathway which displays pleiotropic biological
      effects, including anti-tumor and anti-angiogenic activity. Previous evidence
      revealed a biphasic effect of iPA on phytohemagglutinin-stimulated lymphocytes,
      being pro-proliferative at low doses and anti-proliferative at high doses.
      Analogously, we have recently shown that low iPA concentrations (<1MUM) increased
      the immune response of natural killer (NK) cells against cancer targets. In the
      present study, we evaluated the effect of iPA at high concentration (10MUM) on IL
      2-activated NK cells. iPA, inhibited NK cell proliferation and cytotoxicity
      against their conventional tumor target, human K562 cells. This inhibition was
      associated with decreased expression and functionality of NK cell activating
      receptors NKp44 and NKG2D as well as impaired cyto/chemokines secretion (RANTES,
      MIP-1alpha, TNF-alpha and IFN-gamma). ERK/MAPK and STAT5 activation in IL-2
      activated NK cells were inhibited by iPA. The results obtained in vitro were
      validated in vivo in the inflammatory murine model of croton oil-induced ear
      dermatitis. The topical application of iPA significantly reduced mouse ear
      oedema, thus suggesting anti-inflammatory properties of this molecule. These
      results show the ability of iPA to exert anti-inflammatory effects both in vitro
      and in vivo directly targeting NK cells, providing a novel pharmacological tool
      in those diseases characterized by a deregulated immune-response, such as cancer
      or inflammatory conditions. 

PMID- 25063360
TI  - Clostridium vulturis sp. nov., isolated from the intestine of the cinereous
      vulture (Aegypius monachus).
AB  - A Gram-stain positive, strict anaerobe, spore-forming, motile rod-shaped
      bacterial strain with peritrichous flagella, designated YMB-57(T), was isolated
      from the intestine of a cinereous vulture (Aegypius monachus) in Korea. Strain
      YMB-57(T) was found to show optimal growth at 37  degrees C, pH 7.5 and 1.0 %
      (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence showed that
      strain YMB-57(T) belongs to the genus Clostridium and is most closely related to
      the type strains of Clostridium subterminale (96.9 % sequence similarity),
      Clostridium thiosulfatireducens (96.7 %) and Clostridium sulfidigenes (96.6 %).
      The main fermentation end-products identified following growth in PYG medium were
      acetate, butyrate, ethanol, propanol, carbon dioxide and hydrogen. Peptone was
      converted to ethanol, and butanol, whereas glucose was fermented to ethanol. The
      major cellular fatty acids were identified as C16:0, C18:1 omega9c, and C18:1
      omega9c DMA and the DNA G+C content was determined to be 34.0 mol%. Phenotypic
      and phylogenetic differences indicate that strain YMB-57(T) is distinct from
      other Clostridium species. It is proposed that strain YMB-57(T) be classified as
      the type strain of a novel species of the genus Clostridium, with the name
      Clostridium vulturis sp. nov. The type strain is YMB-57(T) (=KCTC 15114(T) = JCM
      17998(T)).

PMID- 25063361
TI  - Timing-dependent priming effects of tDCS on ankle motor skill learning.
AB  - Transcranial direct current stimulation (tDCS) has gained increasing interest in
      neurorehabilitation with its ability to modulate cortical excitability, and
      thereby influence neural plasticity and functional recovery. While the beneficial
      effects of tDCS on motor learning and function have been recognized, there is no
      clear consensus regarding the timing of the tDCS priming protocol in relation to
      the intervention especially with respect to lower limb motor learning. Depending
      on the time of priming in relation to the training task, the neural mechanisms of
      priming (gating vs. homeostatic plasticity) are different and thereby
      subsequently affect motor learning. Hence, the aim of this study was to examine
      the interaction of tDCS with subsequent vs. concurrent motor learning using an
      ankle visuomotor skill learning paradigm. Twelve healthy participants were tested
      under three stimulation conditions: (1) anodal tDCS prior to the motor task (tDCS
      before), (2) anodal tDCS during the motor task (tDCS-during) and (3) sham tDCS
      during the motor task (tDCS-sham). Results revealed that tDCS application during
      practice of a skilled motor task increased motor performance compared to tDCS
      applied prior to motor practice. Both tDCS groups demonstrated enhanced motor
      learning when tested 24 hours after practice. We conclude that the priming
      effects of tDCS are timing dependent, and maybe a critical regulatory feature in
      determining outcomes of priming with tDCS.

PMID- 25063363
TI  - Increasing health inequalities between women in and out of work--the impact of
      recession or policy change? A repeated cross-sectional study in Stockholm county,
      2006 and 2010.
AB  - INTRODUCTION: The social insurance system in Sweden underwent extensive change
      between 2006 and 2010, with the overall aim of making people enter the labour
      market. At the same time, economic recession hit Sweden. Previous studies suggest
      that the economic recession particularly affected women. In light of these
      changes, the aim of this study is to investigate whether health inequalities
      between employed women and groups outside the labour market changed between 2006
      and 2010. A second aim is to examine the explanatory weight of socio-demographic
      factors vs social and economic conditions. METHODS: Data consists of the
      Stockholm Public Health Surveys (SPHS) for 2006 and 2010. Women aged 18-64 were
      studied. Through logistic regression, levels of mental distress and limiting
      longstanding illness (LLI), were compared between four labour market groups;
      employed and unemployed, sickness absentees and disability pension recipients, at
      the two time points. RESULTS: Mental distress increased among women in all four
      labour market groups between 2006 and 2010. Differences in mental distress
      between those employed and groups outside the labour market also increased. These
      were explained primarily by social and economic conditions. Levels of LLI were
      unchanged except among the unemployed. The difference in LLI between the
      unemployed and the employed was mostly explained by social and economic
      conditions. In the other groups socio-demographic factors were more salient. For
      both health outcomes, the weight of social and economic conditions had increased
      in 2010 compared to 2006. CONCLUSIONS: Results indicate that levels of mental
      distress increased in all groups, but more so among groups outside the labour
      market, possibly due to stricter eligibility criteria and lower benefit levels,
      which particularly affected their social and economic conditions.

PMID- 25063362
TI  - Circadian modulation of memory and plasticity gene products in a diurnal species.
AB  - Cognition is modulated by circadian rhythms, in both nocturnal and diurnal
      species. Rhythms of clock gene expression occur in brain regions that are outside
      the master circadian oscillator of the suprachiasmatic nucleus and that control
      cognitive functions, perhaps by regulating the expression neural-plasticity genes
      such as brain derived neurotrophic factor (BDNF) and its high affinity receptor,
      tyrosine kinase B (TrkB). In the diurnal grass rat (Arvicanthis niloticus), the
      hippocampus shows rhythms of clock genes that are 180 degrees  out of phase with
      those of nocturnal rodents. Here, we examined the hypothesis that this reversal
      extends to the optimal phase for learning a hippocampal-dependent task and to the
      phase of hippocampal rhythms in BDNF/TrkB expression. We used the Morris water
      maze (MWM) to test for time of day differences in reference memory and monitored
      daily patterns of hippocampal BDNF/TrkB expression in grass rats. Grass rats
      showed superior long-term retention of the MWM, when the training and testing
      occurred during the day as compared to the night, at a time when nocturnal
      laboratory rats show superior retention; acquisition of the MWM was not affected
      by time of day. BDNF/TrkB expression was rhythmic in the hippocampus of grass
      rats, and the phase of the rhythms was reversed compared to that of nocturnal
      rodents. Our findings provide correlational evidence for the claim that the
      circadian regulation of cognition may involve rhythms of BDNF/TrkB expression in
      the hippocampus and that their phase may contribute to species differences in the
      optimal phase for learning. 

PMID- 25063364
TI  - Foxp3 expression in T regulatory cells and other cell lineages.
AB  - Forkhead box P3 (Foxp3) is an important transcription factor that belongs to the
      forkhead/winged-helix family of transcriptional regulators. Foxp3 has been
      extensively studied over the past 13 years as a master regulator of transcription
      in a specific T-cell type, CD4(+) regulatory T cells (Treg), both in humans and
      in mice. Compelling data characterize Foxp3 as critically important and necessary
      for the development and the differentiation of Treg. It has been considered
      initially as the only specific marker for Treg. However, recent work has proposed
      that Foxp3 can be expressed by other types of lymphoid cells or myeloid cells and
      also by some non-hematopoietic cells such as epithelial cells. It remains
      controversial about the expression of Foxp3 in cells other than Treg, but
      understanding the potential expression and function of this master regulator in
      different cell subsets could have a wide range of implications for immune
      tolerance and several pathologies including autoimmune disorders and immune
      responses to cancer. 

PMID- 25063365
TI  - Posterior reversible encephalopathy syndrome after depletive lumbar puncture: a
      case report.
AB  - INTRODUCTION: Posterior reversible encephalopathy syndrome is a rare entity. Its
      pathophysiology is still poorly understood. CASE PRESENTATION: We report the case
      of a 69-year-old White European woman who presented complete and proportional
      right hemiplegia, confusion, deviation of her head and eyes to the right,
      cortical blindness, and generalized tonic-clonic seizure 12 hours following a
      depletive lumbar puncture. Emergency cerebral magnetic resonance imaging showed
      bioccipital and left-side basal ganglia hyperintensities in the fluid attenuated
      inversion recovery and the diffusion-weighted images suggesting a radiological
      diagnosis of posterior reversible encephalopathy syndrome. CONCLUSIONS: The
      diagnosis is established on clinical and radiological signs. This is the first
      report of this kind in the literature. We present a case of posterior reversible
      encephalopathy syndrome after depletive lumbar puncture and we discuss the
      pathophysiology.

PMID- 25063366
TI  - A novel computerized algorithm to detect microstructural brainstem pathology in
      Parkinson's disease using standard 3 Tesla MR imaging.
AB  - Increased deposition of alpha-synuclein in Parkinson's disease (PD) is known to
      be prominent in the brainstem and discussed to be clinically relevant for motor
      and non-motor features. Whether structural magnetic resonance imaging is capable
      to detect degraded tissue microstructure caused by increased deposition of alpha
      synuclein at this predilection site in PD remains unclear. We hypothesize that
      microstructural degradation in the brainstem leads to a reduced T1 contrast
      provoking standard tissue segmentation engines to misclassify tissue as
      additional grey matter in regions predominantly composed of white matter. High
      resolution T1-weighted three-dimensional magnetization prepared rapid gradient
      echo (MPRAGE) imaging at 3 Tesla in fifty-two PD patients with mild-to-moderate
      disease severity and in forty age- and gender-matched healthy controls was
      performed. A dedicated computerized algorithm that comprises standard tissue
      segmentation in combination with a statistical test was set up that evaluates
      grey matter composition on voxel level. The algorithm detected a single
      significant cluster of voxels with enhanced grey matter (cluster volume is 1,368
      mm(3), p < 0.05 corrected for false discovery rate) in the pontomedullary
      junction of the brainstem in PD patients as compared to healthy controls.
      Furthermore, absolute grey matter volume was significantly higher in the
      brainstem of the PD group compared to healthy controls. We conclude that this
      cluster may reflect alpha-synuclein induced microstructural brainstem pathology
      in PD.

PMID- 25063367
TI  - The role of cAMP dependent protein kinase in modulating spontaneous intracellular
      Ca2+ waves in interstitial cells of Cajal from the rabbit urethra.
AB  - Interstitial cells of Cajal (ICC) serve as electrical pacemakers in the rabbit
      urethra. Pacemaking activity in ICC results from spontaneous intracellular Ca(2+)
      waves that rely on Ca(2+) release from endoplasmic reticulum (ER) stores. The
      purpose of this study was to investigate if the action of protein kinase A (PKA)
      affected the generation of Ca(2+) waves in ICC. Intracellular [Ca(2+)] was
      measured in fluo-4 loaded ICC, freshly isolated from the rabbit urethra using a
      Nipkow spinning disc confocal microscope. Application of the PKA inhibitor H-89
      (10 MUM) significantly inhibited the generation of spontaneous Ca(2+) waves in
      ICC and this was associated with a significant decrease in the ER Ca(2+) load,
      measured with 10mM caffeine responses. Ca(2+) waves could be rescued in the
      presence of H-89 by stimulating ryanodine receptors (RyRs) with 1mM caffeine but
      not by activation of inositol 1,4,5 tri-phosphate receptors (IP3Rs) with 10 MUM
      phenylephrine. Increasing intracellular PKA with the cAMP agonists forskolin and
      8-bromo-cAMP failed to yield an increase in Ca(2+) wave activity. We conclude
      that PKA may be maximally active under basal conditions in ICC and that
      inhibition of PKA with H-89 leads to a decreased ER Ca(2+) load sufficient to
      inactivate IP3Rs but not RyRs.

PMID- 25063368
TI  - Child self-reported motivations for weight loss: impact of personal vs.
      social/familial motives on family-based behavioral weight loss treatment
      outcomes.
AB  - PURPOSE: Parent motivation is related to successful treatment outcome among
      children enrolled in obesity treatment. However, the impact of child weight loss
      motivation on treatment outcome has not been investigated. The current study
      evaluated weight loss motives among treatment-seeking, overweight children, and
      their relationship to treatment outcome. METHODS: The current study is a
      secondary analysis of a primary study examining a parent-only and parent + child
      childhood obesity treatment. Study participants included 77 children (aged 8-12,
      58 % female). Assessments were completed at baseline, post-treatment, and at 6
      months post-treatment. Children completed standardized height and weight
      procedures. In addition, they completed a checklist of reasons children may be
      motivated to lose weight. Motives were divided into two scales reflecting
      personal and social/familial reasons to lose weight. Regression analyses were
      used to calculate associations between the number of weight loss motives endorsed
      and treatment completion, sessions attended, and child BMI. RESULTS: A greater
      number of social/familial motives were significantly predictive of session
      attendance, treatment completion, and a lower child BMI at the post-treatment
      assessment. CONCLUSIONS: Children who are motivated to lose weight because of
      family/social influences may be more highly engaged in treatment and lose more
      weight, as compared to children who are less motivated by family and social
      reasons.

PMID- 25063370
TI  - Effects of physiochemical properties of test media on nanoparticle toxicity to
      Daphnia magna Straus.
AB  - The physicochemical property of standard test media significantly influenced the
      aggregation and dissolution of Ag, CuO and ZnO nanoparticles (NPs) and the
      toxicity of the NPs to Daphnia magna. For all the NPs, the highest amount of
      metal ions was released from the ISO medium, whereas acute toxicity to D. magna
      was highest in the moderately hard water medium (EC50 = 4.94, 980, and 1,950 MUg
      L(-1) for Ag, CuO, and ZnO, respectively). By comparing EC50 values based on the
      total and dissolved concentrations of NPs with those of metal salt solutions, we
      found that both particulate and dissolved fractions were likely responsible for
      the toxicity of Ag NPs, whereas the dissolved fraction mostly contributed to the
      toxicity of CuO and ZnO NPs.

PMID- 25063369
TI  - Modic (endplate) changes in the lumbar spine: bone micro-architecture and
      remodelling.
AB  - PURPOSE: In the literature, inter-vertebral MRI signal intensity changes (Modic
      changes) were associated with corresponding histological observations on endplate
      biopsies. However, tissue-level studies were limited. No quantitative
      histomorphometric study on bone biopsies has yet been conducted for Modic
      changes. The aim of this study was to characterise the bone micro-architectural
      parameters and bone remodelling indices associated with Modic changes. METHODS:
      Forty patients suffering from disabling low back pain, undergoing elective spinal
      surgery, and exhibiting Modic changes on MRI (Modic 1, n = 9; Modic 2, n = 25;
      Modic 3, n = 6), had a transpedicular vertebral body biopsy taken of subchondral
      bone. Biopsies were first examined by micro-CT, for 3D morphometric analysis of
      bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular
      separation, trabecular number, and structure model index. Then, samples underwent
      histological analysis, for determination of bone remodelling indices: osteoid
      surface to bone surface ratio (OS/BS), eroded surface to bone surface (ES/BS) and
      osteoid surface to eroded surface ratio (OS/ES). RESULTS: Micro-CT analysis
      revealed significantly higher BV/TV (up to 70% increase, p < 0.01) and Tb.Th (up
      to +57%, p < 0.01) in Modic 3 biopsies, compared to Modic 1 and 2. Histological
      analysis showed significantly lower OS/BS in Modic 2 biopsies (more than 28%
      decrease, p < 0.05) compared to 1 and 3. ES/BS progressively decreased from Modic
      1 to 2 to 3, whereas OS/ES progressively increased with significantly higher
      values in Modic 3 (up to 159% increase, p < 0.05) than in Modic 1 and 2.
      CONCLUSIONS: Significant differences were found in bone micro-architectural
      parameters and remodelling indices among Modic types. Modic 1 biopsies had
      evidence of highest bone turnover, possibly due to an inflammatory process; Modic
      2 biopsies were consistent with a reduced bone formation/remodelling stage; Modic
      3 biopsies suggested a more stable sclerotic phase, with significantly increased
      BV/TV and Tb.Th compared to Modic 1 and 2, linked to increased bone formation and
      reduced resorption.

PMID- 25063371
TI  - Monitoring of 137Cs fallout in Syrian environment.
AB  - This paper presents measurements of cesium 137 ((137)Cs) in the Syrian
      environment during the period between 2006 and 2010. More than 1,000 samples of
      soil, water, plants and aquatic life were collected from different locations. The
      measurements were realized using gamma spectroscopy, and the results showed that
      radioactivity concentrations were low overall. Concentrations ranged from below
      detection limits to several tens Bq kg(-1) (dry matter) or 9.8 mBq L(-1) (water),
      which were well below maximum allowable levels in food or drinking water as
      established according to Syrian national standards or the WHO/FAO Codex
      guidelines. However, high (137)Cs activity levels were observed in soil samples
      collected at a high elevation (Kadmous highs), where a mean concentration of
      1,900 Bq kg(-1) was obtained.

PMID- 25063372
TI  - PQRST - a unique aide-memoire for capnography interpretation during cardiac
      arrest.
AB  - The use of capnography is recommended during resuscitation. By implementing the
      mnemonic "PQRST", rescuers have a ready-made checklist to help them achieve the
      full potential of capnography. This approach can facilitate efforts to both
      reduce the hands-off time and individualize the treatment, which can lead to
      improved survival for our patients. 

PMID- 25063373
TI  - Sedation management during therapeutic hypothermia for neonatal encephalopathy:
      atropine premedication for endotracheal intubation causes a prolonged increase in
      heart rate.
AB  - AIM: Heart rate (HR) plays an important role in the assessment of stress during
      therapeutic hypothermia (TH) for neonatal encephalopathy; we aimed to quantify
      the effect on HR of endotracheal (ET) intubation and drugs given to facilitate
      it. If atropine premedication independently increased HR, the main indicator of
      effective sedation, we hypothesised that increased sedation would have been
      given. METHODS: Thirty-two, term, neonates recruited into a randomised pilot
      study comparing TH and TH combined with 50% Xenon inhalation were studied.
      Indications for ET intubation included: resuscitation at delivery, clinical need
      and elective re-intubation with a cuffed ET tube if randomised to Xenon. Standard
      intubation drugs comprised one or more of intravenous morphine, atropine, and
      suxamethonium. Local cooling guidelines were followed including morphine infusion
      for sedation. RESULTS: At postnatal hours five to eight atropine increased HR in
      a linear regression model (p<0.01). All other independent variables were
      excluded. Where more than one dose of atropine was given total morphine sedation
      given up to 8h into the treatment period was significantly higher (p<0.01).
      CONCLUSION: We have shown that atropine premedication for ET intubation
      significantly increased HR, the main indicator of effective sedation and total
      morphine dose for sedation during early TH was increased where more than one dose
      of atropine was given. Bradycardia was not reported in any neonate, even without
      atropine premedication. We suggest that the use of atropine as part of standard
      premedication for ET intubation of term neonates undergoing TH should be
      reconsidered.

PMID- 25063374
TI  - Albumin and glycated albumin activate KIM-1 release in tubular epithelial cells
      through distinct kinetics and mechanisms.
AB  - OBJECTIVE: Kidney injury molecule-1 (KIM-1) serves as a useful marker for
      monitoring tubular injury, and sustained KIM-1 expression may be implicated in
      chronic kidney fibrosis. In this study, we examine the kinetics and mechanisms of
      KIM-1 release in human proximal tubular epithelial cells (PTEC) under the
      activation by major pathologic players in diabetic nephropathy, including human
      serum albumin (HSA), glycated albumin (AGE-BSA) and high glucose. MATERIALS AND
      METHODS: The kinetics of KIM-1 release by PTEC under activation with HSA, AGE-BSA
      and high glucose, were determined by RT-PCR and ELISA. The activation profiles of
      major signaling pathways in PTEC were identified by PCR array. Based on the array
      data, blockade experiments were designed to assess their regulatory roles in KIM
      1 release. RESULTS: Prompt shedding of KIM-1 was observed in PTEC cultured for 4
      h with HSA and AGE-BSA, but not with high glucose. Culturing PTEC for 3 days with
      AGE-BSA exhibited sustained up-regulation of KIM-1 release, but not with HSA. In
      all culture experiments, high glucose did not induce KIM-1 release in PTEC. HSA
      and AGE-BSA activated multiple signaling pathways in PTEC including NFkappaB,
      ERK1/2 and the oxidative stress pathways. Long-term culturing PTEC with AGE-BSA
      but not HSA activated the Jak-Stat pathway. While incubation of PTEC with
      diphenylene iodonium blocked the short-term release of KIM-1 mediated by HSA or
      AGE-BSA, Jak-Stat inhibitors diminished the long-term KIM-1 release by PTEC
      induced by AGE-BSA. CONCLUSION: KIM-1 release in PTEC was differentially up
      regulated by HSA and AGE-BSA. The short-term KIM-1 shedding was mediated by the
      reactive oxygen species, whereas Jak-Stat pathway regulates the long-term KIM-1
      release.

PMID- 25063375
TI  - Dynamics of mitochondrial RNA-binding protein complex in Trypanosoma brucei and
      its petite mutant under optimized immobilization conditions.
AB  - There are a variety of complex metabolic processes ongoing simultaneously in the
      single, large mitochondrion of Trypanosoma brucei. Understanding the organellar
      environment and dynamics of mitochondrial proteins requires quantitative
      measurement in vivo. In this study, we have validated a method for immobilizing
      both procyclic stage (PS) and bloodstream stage (BS) T. brucei brucei with a high
      level of cell viability over several hours and verified its suitability for
      undertaking fluorescence recovery after photobleaching (FRAP), with mitochondrion
      targeted yellow fluorescent protein (YFP). Next, we used this method for
      comparative analysis of the translational diffusion of mitochondrial RNA-binding
      protein 1 (MRP1) in the BS and in T. b. evansi. The latter flagellate is like
      petite mutant Saccharomyces cerevisiae because it lacks organelle-encoded nucleic
      acids. FRAP measurement of YFP-tagged MRP1 in both cell lines illuminated from a
      new perspective how the absence or presence of RNA affects proteins involved in
      mitochondrial RNA metabolism. This work represents the first attempt to examine
      this process in live trypanosomes. 

PMID- 25063376
TI  - Effect on metabolic enzymes and thyroid receptors induced by BDE-47 by activation
      the pregnane X receptor in HepG2, a human hepatoma cell line.
AB  - 2,2',4,4'-Tetra-bromodiphenyl ether (BDE-47), an important congener among
      polybrominated diphenyl ether (PBDE) compounds, has been predominantly in
      environmental samples and human tissue. Thyroid disruption is the most sensitive
      endpoint effect among a number of health effects of exposure to BDE-47 in animals
      and humans. However, the detailed underlying mechanisms in humans are not well
      understood. In the present study, human pregnane X receptor (hPXR)-overexpressing
      HepG2 cell model and a dual-luciferase reporter assay system were constructed to
      investigate the role of hPXR in BDE-47-induced alterations of expression of
      metabolic enzymes and TR in vitro. The results showed that hPXR was significantly
      activated by BDE-47, and expression levels of both mRNA and protein of the
      thyroid receptor (TR) isoforms TRalpha1 and TRbeta1 were decreased in hPXR
      overexpressing HepG2 cells after BDE-47 treatment. However, the increased
      expression of hepatic microsomal phase I enzyme CYP3A4 and phase II enzymes,
      UGT1A3 and SULT2A1 were also found. Taken together, the results indicated that
      BDE-47 was a strong hPXR activator, activation of hPXR played an important role
      in BDE-47-induced down-regulation of TR, and up-regulations of CYP3A4, UGT1A3,
      and SULT2A1 participated in the process, which may provide more toxicological
      evidence on mechanisms of disruption of thyroid hormone induced by BDE-47.

PMID- 25063377
TI  - Identification of conserved and novel microRNAs in cerebral ischemia-reperfusion
      injury of rat using deep sequencing.
AB  - MicroRNAs are a class of noncoding small RNAs that regulate gene expression by
      inhibiting target genes at post-transcriptional levels. MicroRNAs have been
      highlighted in many organs and tissues, including the brain. To identify special
      microRNAs involved in ischemia-reperfusion injury, we performed a comprehensive
      small RNA profiling in rat model and the control using Illumina high-throughput
      sequencing. A total of 9,444,562 and 10,290,391 clean reads were sequenced from
      two small RNA libraries constructed, respectively. Three hundred fifty-eight
      known microRNAs were identified, in which 78 microRNAs exhibited significantly
      differential expression between model and control. In addition, 62 and 68 novel
      miRNAs were found in model and control, respectively. Comparative analysis showed
      that 24 novel microRNAs were differentially expressed with greater than six-fold
      change. The GO annotation suggested that predicted targets of microRNAs were
      enriched into the category of metabolic process, cell part, cell-extracellular
      communications, and so on. KEGG pathway analysis suggested that these genes were
      involved in many important pathways, mainly including signaling transduction,
      MAPK signaling pathway, NF-kappaB signaling pathway, and neurotrophin signaling
      pathway. Our findings provided a deeper understanding to the regulatory mechanism
      of microRNAs underlying cerebral ischemia, therefore benefitting the improvement
      of the protection and treatment strategies of this disease. 

PMID- 25063378
TI  - [Mucopolysaccharidoses: diagnosis and management].

PMID- 25063379
TI  - [Neurologic manifestations in mucopolysaccharidoses].
AB  - Mucopolysaccharidoses (MPS) are progressive multisystem lysosomal storage
      diseases caused by defective catabolism of complex molecules, namely the
      glycosaminoglycans and their consequent accumulation in tissues. Of the 7
      clinical types representing 11 different enzyme deficiencies, only MPS III
      (Sanfilippo syndromes A, B, C and D) and severe forms of MPS I (Hurler's
      syndrome), MPS II (severe Hunter syndrome) and MPS VII (severe Sly syndrome) give
      rise to progressive cerebral disease. Neurosensory complications (hearing
      impairment, retinopathy and optic atrophy) can also occur in some types. Carpal
      (or even tarsal) tunnel syndrome is a common complication of the MPS, except for
      MPS III and MPS IV. Hydrocephalus due to abnormal circulation or resorption of
      cerebrospinal fluid, chronic spinal compression may occur as complications of MPS
      I, II and VII and also in MPS IV and VI. Atlanto-axial instability may be
      observed in type IV and I. 

PMID- 25063380
TI  - [Genetic aspects of mucopolysaccharidoses].
AB  - Mucopolysaccharidoses (MPS) are inherited metabolic diseases caused by mutations
      in the genes coding for one of the eleven enzymes involved in lysosomal
      catabolism of different glycosaminoglycans (or mucopolysaccharides). The
      different enzyme deficiencies result in a total of seven distinct
      mucopolysaccharidoses (I to IV, VI, VII and IX). This review considers the
      genetic and molecular aspects of the seven types of MPS. 

PMID- 25063381
TI  - [Laboratory diagnosis and follow up of mucopolysaccharidoses].
AB  - Mucopolysaccharidoses (MPS) often raise diagnostic challenges, particularly in
      patients with progressive disease and relatively non-specific signs and symptoms.
      Early diagnosis improves management and enables to start specific treatment when
      available. Each type of MPS is associated with a deficiency of a lysosomal enzyme
      which catalyses the degradation of glycosaminoglycans (GAGs). The initial
      diagnosis Wis suggested by quantifying and identifying the accumulated
      metabolites. Diagnosis is then confirmed by assaying the deficient enzyme,
      allowing diagnosis in a large majority of cases. Indirect markers, which do not
      arise directly from the deficient metabolic pathway and vary in concentration
      depending on the degree of disease progression, are used to support a diagnosis
      of MPS and/or monitor the efficacy of the specific treatment. Identifying the
      underlying genic abnormality enables family studies to be carried out and perform
      prenatal diagnosis. 

PMID- 25063382
TI  - [Natural history of Morquio A disease].
AB  - Type IV mucopolysaccharidosis (Morquio A syndrome; MPS IVA; OMIM 253000), is a
      multisystemic, severe and very disabling disease, also life-threatening; MPS IVA
      is due to a deficiency of the enzyme N-acetylgalactosamine-6-sulfate sulfatase
      (GALNS), a lysosomal enzyme responsible for the degradation of keratan sulfate
      (KS) and chondroitin-6-sulfate (C6S). The disease is characterized by
      respiratory, pulmonary manifestations and also causes bone involvement with
      progressive spondyloepimetaphyseal degradation and mild and late-onset
      ophthalmologic, hearing and cardiac complications. These manifestations
      progressively impair the patients' physical mobility. Severe forms of the
      disease, diagnosed before the age of 1 year, can be distinguished from
      intermediary (diagnosed between 1 and 5 years old) and attenuated disease,
      diagnosed after the age of 5 years (occasionally far later). The main signs are
      bone deformities namely pectus carinatum, kyphoscoliosis and genu valgum, with
      early flattening of the growth curve, leading rapidly to almost complete growth
      arrest. Patients have normal cognitive development. The radiological signs are
      relatively specific with, in particular, platyspondyly, shortening of the long
      bones and characteristic pelvic changes. The diagnosis is suggested by elevated
      urinary GAGs level and profile, and is confirmed by GALNS enzymatic studies on
      molecular testing. Genetic counseling is important in this autosomal recessive
      disorder and enzymatic and/or molecular testing can be offered for prenatal
      diagnosis. Management is mostly symptomatic, based on early detection and
      orthopedic correction of spine and lower limb deformities, ENT and respiratory
      management and psychological, social and educational support for the child and
      his/her family. 

PMID- 25063383
TI  - [Principles of therapeutic approaches for mucopolysaccharidoses].
AB  - Mucopolysaccharidoses (MPS) are caused by a deficiency of enzymes involved in the
      catabolism of glycosaminoglycans (GAGs) and are multisystemic diseases, often
      including the central nervous system. Despite their rare prevalence, specific
      treatments for MPS are available. One of them is enzyme replacement therapy,
      which provides the missing enzyme in the form of a recombinant protein
      administered intravenously. The effectiveness of this treatment relies on the
      enzymes being taken up by the different tissues via mannose-6-phosphate
      receptors. Treatment is currently available for MPS I, II and VI, and may be
      available for other forms of the disease in the near future. An alternative in
      MPS I is hematopoietic stem cell transplantation, the indications for which must
      be very clearly defined, particularly given the inherent risks of the procedure.
      Other new treatment strategies are currently being investigated, including
      substrate reduction therapy which uses GAG biosynthesis inhibitors
      (genistein,...), which reduces the accumulation of pathological compounds and
      their repercussions on tissues. Other molecular therapies using molecular
      chaperones or read-through molecules for stop codon mutations are also being
      studied. Finally, gene therapy, by introducing a normal gene sequence through a
      viral vector, either directly or using genetically modified cells, is a potential
      future method (the first clinical trials are undergoing). 

PMID- 25063384
TI  - [Bone dysplasia in mucopolysacchoridoses].
AB  - Mucopolysaccharidoses (MPS) are a group of disorders characterized by the
      accumulation of glycosaminoglycans. Skeletal abnormalities are early and
      prominent features of MPS. Cervical spine and atlantoaxial instability,
      thoracolumbar kyphosis, hip dysplasia and osteonecrosis, genu valgum, and carpal
      tunnel syndrome are frequently observed. MPS disease-awareness is important for
      pediatric healthcare providers who should be able to recognize the clinical
      presentation, musculoskeletal abnormalities, and radiographic findings associated
      with this group of disorders. 

PMID- 25063385
TI  - [Global functional management of mucopolysaccharidoses].
AB  - The management of mucopolysaccharidoses (MPS) requires a multidisciplinary
      approach and all medical and paramedical specialties may be involved because of
      the multiorgan nature of the disease. For this reason, patients should ideally be
      managed in a reference center and their management should be coordinated by an
      experienced physician who has access to the various specialists through a multi
      disciplinary approach. The management is focused on assessments of the numerous
      features of the disease, study their progression and the effectiveness and
      pitfalls of specific and non-specific treatments. The main concerns of
      reeducation and rehabilitation should be to preserve global function through
      specific goals to be set along with the child and its family. This is a very
      demanding approach for the patient and family in which education plays a
      fundamental role in order to ensure optimal management. 

PMID- 25063386
TI  - Measurement of implant stability and auditory pure-tone thresholds of Baha
      patients comparing osteosysthesis and osseointegrated systems.
AB  - With bone-anchored hearing systems the implant-bone junction is critical for the
      transmission of mechanical vibrations to the skull. The implant stability might
      differ between available and widely applied implants and can be estimated by
      resonance frequency analysis. The implant stability and the audiological
      performance of ten adult long-time users where a bone-anchored hearing system was
      connected by an Baha osseointegrated implant (Cochlear Ltd, Molnlycke, Sweden)
      were compared with the implant stability of fourteen adult patients provided with
      a Ti-epiplating osteosysthesis system (Medicon, Tuttlingen, Germany). The acute
      implant stability was compared between these two implants with one cadaveric
      skull. The results show higher resonance frequencies and thus higher implant
      stability for the osseointegrating system of both, measuring acute and after long
      time use of the implants. The audiological outcomes show frequency dependent
      differences between both systems as determined by comparing pure-tone bone
      conduction audiometry. However, measuring thresholds by a direct stimulation of
      the implant reveals better hearing with low frequencies for the osseointegrated
      system and for high frequencies with the osteosysthesis system. At all, the
      implant selection has an impact on the implant stability and on the pure-tone
      hearing. 

PMID- 25063387
TI  - Characterisation of camel breeding practices in the Ansongo Region, Mali.
AB  - Despite its importance in Mali's economy, camel breeding in the country remains
      poorly documented, impeding effective policy-making in this regard. This study
      consisted in a 3-month survey and aimed at characterising camel breeding systems
      in Ansongo, in the region of Gao, Mali. It highlights the diversity of strategies
      adopted by breeders and their evolutions. Supplementary feeding and veterinary
      care were seldom practised. In zones close to the Niger River, cattle were
      substituted to camels. Transhumance routes also are modified but mobility keeps
      its vital role in the breeding system. Important differences within the study
      region in the classification of camel breeds have been reported that will
      influence the implementation of a collective action for animal genetic
      improvement. The improvement goals should take the actual management, including
      mobility and the mixed nature of the herds into account. 

PMID- 25063388
TI  - Man-biting sand fly species and natural infection with the Leishmania
      promastigote in leishmaniasis-endemic areas of Ecuador.
AB  - A countrywide surveillance of sand flies was performed to obtain information on
      their geographical distribution and natural infection by Leishmania protozoa in
      Ecuador. A total of 18,119 sand flies were collected by human landing collections
      during 32 years from 1982 to 2014, and 29 species were recognized. The most
      prevalent 10 species were Lutzomyia gomezi, Lu. robusta, Lu. hartmanni, Lu.
      shannoni, Lu. trapidoi, Lu. panamensis, Lu. maranonensis, Lu. ayacuchensis, Lu.
      tortura and Lu. yuilli yuilli, and their topographical and vertical distributions
      were identified. Among all the sand flies, only 197 (1.09%) flies of four
      Lutzomyia species, Lu. gomezi, Lu. trapidoi, Lu. tortura and Lu. ayacuchensis,
      were positive for Leishmania. Endotrypanum, a flagellate parasite not pathogenic
      to humans, were detected in five Lutzomyia species, Lu. robusta, Lu. hartmanni,
      Lu. trapidoi, Lu. panamensis and Lu. yuilli yuilli, suggesting wide vector-ranges
      of Endotrypanum species. These data on the genus Lutzomyia and their natural
      infections with Leishmania and Endotrypanum will be useful for transmission
      studies and surveillance of leishmaniasis. 

PMID- 25063389
TI  - Anthelmintic constituents from ginger (Zingiber officinale) against Hymenolepis
      nana.
AB  - This study investigated the anthelmintic activity of gingerenone A, [6]
      dehydrogingerdione, [4]-shogaol, 5-hydroxy-[6]-gingerol, [6]-shogaol, [6]
      gingerol, [10]-shogaol, [10]-gingerol, hexahydrocurcumin, 3R,5S-[6]-gingerdiol
      and 3S,5S-[6]-gingerdiol, a constituent isolate from the roots of ginger, for the
      parasite Hymenolepis nana. The cestocidal activity or ability to halt spontaneous
      parasite movement (oscillation/peristalsis) in H. nana of above constituents was
      reached from 24 to 72h in a time- and dose-dependent manner, respectively. The
      [10]-shogaol and [10]-gingero1 have maximum lethal efficacy and loss of
      spontaneous movement than the others at 24-72h. In addition, worms treated with 1
      and 10MUM [10]-gingero1, more than 30% had spontaneous movement of oscillation at
      72h but [10]-shogaol at 72h only about 15-20% of oscillation. This showing that
      [10]-gingero1 had less loss of spontaneous movement efficacy than [10]-shogaol.
      After exposure to 200MUM [10]-shogaol, 100% of H. nana had died at 12h rather
      than died at 24h for [10]-gingerol, showing that [10]-gingero1 had less lethal
      efficacy than [10]-shogaol. In addition, these constituents of ginger showed
      effects against peroxyl radical under cestocidal activity. In order to evaluate
      the cestocidal activity and cytokine production caused by ginger's extract R0 in
      the H. nana infected mice, we carried out in vivo examination about H. nana
      infected mice BALB/c mice were inoculated orally with 500 eggs. After post
      inoculation, R0 (1g/kg/day) was administered orally for 10 days. The R0 exhibited
      cestocidal activity in vivo of significantly reduced worms number and cytokines
      production by in vitro Con A-stimulated spleen cells showed that INF-gamma and IL
      2 were significantly increases by R0. IL-4, IL-5, IL-6, IL-10 and IL-13 were
      significantly decreases and Murine KC and IL-12 were not significantly changes by
      R0. Together, these findings first suggest that these constituents of ginger
      might be used as cestocidal agents against H. nana. 

PMID- 25063390
TI  - Acroparesthesia and carpal tunnel syndrome: a historical perspective.
AB  - This article presents the history of acroparesthesia and its contribution to the
      discovery of idiopathic carpal tunnel syndrome (CTS). We used primary sources
      from the middle of the nineteenth century onward to show that the first short
      descriptions of patients with nocturnal and early morning paresthesias, numbness,
      pain, and weakness in the hands, without accompanying physical signs, were
      published around 1850. The condition was named acroparesthesia in 1890 and, in
      the following years, was accepted as a disease in medical textbooks. Almost all
      of the patients with acroparesthesia, described at the end of the nineteenth and
      the first half of the twentieth century, would today be diagnosed with idiopathic
      CTS. Although physicians proposed many hypotheses for the etiology of
      acroparesthesia throughout its 100-year history, they did not understand that the
      condition arose from compression of the median nerve in the carpal tunnel, and
      the concept of acroparesthesia did not lead to the discovery of CTS. Even Russell
      Brain-who, in 1946 and 1947, showed that the "syndrome of partial thenar atrophy"
      was due to compression of the median nerve in the carpal tunnel-did not realize
      that acroparesthesia shared the same origin. This understanding developed in the
      late 1940s and through the 1950s, and the disease came to be accepted under the
      name carpal tunnel syndrome. 

PMID- 25063391
TI  - Upper limb reinnervation in C6 tetraplegia using a triple nerve transfer: case
      report.
AB  - Restoration of elbow extension, grasp, key pinch, and release are major goals in
      low-level tetraplegia. Traditionally, these functions are achieved using tendon
      transfers. In this case these goals were achieved using nerve transfers. We
      present a 21-year-old man with a C6 level of tetraplegia. The left upper limb was
      treated 6 months after injury with a triple nerve transfer. A teres minor nerve
      branch to long head of triceps nerve branch, brachialis nerve branch to anterior
      interosseous nerve, and supinator nerve branch to posterior interosseous nerve
      transfer were used successfully to reconstruct elbow extension, key pinch, grasp,
      and release simultaneously. 

PMID- 25063392
TI  - Carpal tunnel syndrome, syndrome of partial thenar atrophy, and W. Russell Brain:
      a historical perspective.
AB  - This article presents the history of the discovery of compression of the median
      nerve in the carpal tunnel without an identifiable cause as a distinct clinical
      entity. By analyzing primary sources, we show that, at the beginning of the
      twentieth century, physicians described patients with paresthesias and numbness
      in the hands, most prominent at night, accompanied by bilateral symmetrical
      atrophy along the radial side of thenar eminence. At the time, the 2 most
      influential hypotheses regarding etiology were, first, compression of the lower
      trunk of the brachial plexus by a cervical or first rib, and second, compression
      of the thenar branch of the median nerve as it passes beneath the anterior
      annular ligament of the wrist. The condition was named syndrome of partial thenar
      atrophy and was considered a distinct clinical entity. In 1946, after extensive
      analysis, neurologist Walter Russell Brain concluded that both sensory and motor
      symptoms of the syndrome were caused by "compression neuritis" of the median
      nerve in the carpal tunnel. At his suggestion, surgeon Arthur Dickson Wright
      performed decompression of the nerve by "an incision of the carpal ligament,"
      with excellent results. Brain presented this work at the Royal Society of
      Medicine in London in 1946 and published his landmark paper in Lancet the
      following year. In so doing, he established the basis for the disease we know
      today as idiopathic carpal tunnel syndrome. Unfortunately, in 1947, Brain did not
      realize that another "condition" with the same clinical picture but without
      atrophy of the thenar muscles, known as acroparesthesia at the time, was actually
      the same disease as syndrome of partial thenar atrophy, but of lesser severity.
      As a result of Brain's influence, 7 other papers were published by 1950. Between
      1946 and 1950, there were at least 10 papers that presented, in total, 31
      patients (26 women) who exhibited symptoms of compression of the median nerve
      without an identifiable cause and underwent section of the transverse carpal
      ligament.

PMID- 25063393
TI  - Discovery elbow system: 2- to 5-year results in distal humerus fractures and
      posttraumatic conditions: a prospective study on 24 patients.
AB  - PURPOSE: To prospectively evaluate preliminary results of the Discovery Elbow
      System (DES) used for acute distal humerus fractures and posttraumatic
      conditions. METHODS: We analyzed 24 patients (9 men and 15 women), with a mean
      age of 69 years (range, 45-89 y). Ten had comminuted distal humerus fractures
      (group I), and 14 had severe post-traumatic arthritis, chronic instability, or
      nonunion (group II). Clinical and radiographic evaluations were performed. The
      preoperative (group II) and postoperative (both groups) evaluations were assessed
      with the Mayo Elbow Performance Score and Mayo Elbow Performance Index, the Quick
      Disabilities of the Arm, Shoulder, and Hand score, and the modified American
      Shoulder and Elbow Surgeons score. Patient satisfaction was evaluated on a 4
      point scale. RESULTS: Mean follow-up was 41 months (range, 29-63 mo). At the last
      evaluation, average flexion, extension, pronation, and supination were 136
      degrees , 17 degrees , 80 degrees , and 83 degrees , respectively. The average
      Mayo Elbow Performance Score, Quick Disabilities of the Arm, Shoulder, and Hand
      score, and the modified American Shoulder and Elbow Surgeons score were 96, 20,
      and 84, respectively, and without significant intergroup differences. According
      to the Mayo Elbow Performance Index, there were 20 excellent, 3 good, and 1 fair
      result. Twenty patients were very satisfied or satisfied with the outcome. A
      significant increase in the functional scores was observed in group II compared
      with preoperative results. Radiological evaluation showed 1 patient with
      progressive radiolucency and 1 with a nonprogressive radiolucency at the final
      follow-up. No mechanical failures were observed. Two transient ulnar
      neuropathies, 1 wound infection, and 1 epicondyle fracture were observed.
      CONCLUSIONS: The DES yielded promising 2- to 5-year results in the treatment of
      acute fractures and posttraumatic conditions regarding pain relief, functional
      improvement, and patient satisfaction, achieving excellent results in most cases.
      The DES may represent an effective linked-implant option for total elbow
      replacement in such patients. However, long-term studies are needed. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25063394
TI  - Embolization of post-biliary sphincterotomy bleeding refractory to medical and
      endoscopic therapy: technical results, clinical efficacy and predictors of
      outcome.
AB  - PURPOSE: To retrospectively analyse the technical and clinical outcomes of
      embolotherapy for post-biliary sphincterotomy bleeding refractory to medical and
      endoscopic therapy, and in addition, to analyse factors potentially influencing
      30-day mortality. MATERIALS AND METHODS: From November 1998 to November 2012, 34
      patients underwent percutaneous embolotherapy for post-biliary sphincterotomy
      bleeding refractory to medical and endoscopic treatment. Demographic, laboratory,
      angiographic, and clinical follow-up data were collected. RESULTS: Indication for
      initial endoscopic sphincterotomy was benign (n = 28) or malignant (n = 6)
      disease. A precut sphincterotomy followed by sphincterotomy was performed in 13
      patients (38 %), whereas the remaining 21 patients (62 %), underwent only
      sphincterotomy. Seven patients (20.6 %) were still on antithrombotic medication
      at the time of sphincterotomy. Angiographic evaluation revealed contrast
      extravasation (n = 31), pseudoaneurysm (n = 2), or a combination of both (n = 1).
      Embolization was successful in 33 of 34 patients (97 %). Recurrent bleeding
      occurred in three patients (9 %), and 30-day mortality was 20.6 % (n = 7).
      Factors significantly influencing 30-day mortality were INR (P = 0.008) and aPTT
      (P = 0.012). CONCLUSION: Angiographic embolization is very effective in stopping
      post-biliary sphincterotomy bleeding refractory to medical and endoscopic
      therapy. The rate of rebleeding is acceptably low, but 30-day mortality remains
      significant. Haemostatic disorders appear to significantly influence 30-day
      survival. KEY POINTS: * Transcatheter embolization is very effective in stopping
      major post-biliary sphincterotomy bleeding * The rate of rebleeding is acceptably
      low * Haemostatic disorders appear to significantly influence 30-day survival.

PMID- 25063395
TI  - Hepatocellular carcinoma: clinical significance of signal heterogeneity in the
      hepatobiliary phase of gadoxetic acid-enhanced MR imaging.
AB  - OBJECTIVES: To clarify the relationship between the biological behaviour of
      hepatocellular carcinomas (HCCs) and their signal intensity in the hepatobiliary
      phase of gadoxetic acid-enhanced MR imaging with a special focus on the signal
      heterogeneity. METHODS: A total of 68 patients with 70 pathologically proven HCCs
      were enrolled. On the basis of the signal intensity in the hepatobiliary phase,
      the lesions were classified into three groups: group 1, homogeneous hypointensity
      (n = 44); group 2, heterogeneous hyperintensity (n = 20); and group 3,
      homogeneous hyperintensity (n = 6). The clinicopathological findings were
      compared among the three groups. RESULTS: The tumour size and the serum level of
      protein induced by vitamin K absence or antagonist-II (PIVKA-II) were
      significantly higher in group 2 compared to group 1 (p = 0.0155, p = 0.0215,
      respectively) and compared to group 3 (p = 0.0330, p = 0.0220, respectively). The
      organic anion transporting polypeptide 8 (OATP8) expression in group 2 and group
      3 was significantly higher than in group 1 (p < 0.0001, p < 0.0001,
      respectively). Group 2 showed a significantly lower disease-free survival rate
      compared to group 1 (p = 0.0125), and group 2 was an independent prognostic
      factor for disease-free survival (p = 0.0308). CONCLUSIONS: HCCs in the
      hepatobiliary phase that are heterogeneously hyperintense on gadoxetic acid
      enhanced MR imaging have more malignant potential than other types of HCCs. KEY
      POINTS: * Heterogeneous uptake of gadoxetic acid suggests more malignant
      potential in HCC * Uptake of gadoxetic acid does not suggest less malignancy in
      HCC * Evaluation of signal heterogeneity on gadoxetic acid-enhanced MR imaging is
      useful.

PMID- 25063397
TI  - Interplay among nocturnal activity, melatonin, corticosterone and performance in
      the invasive cane toad (Rhinella marinus).
AB  - Most animals conduct daily activities exclusively either during the day or at
      night. Here, hormones such as melatonin and corticosterone, greatly influence the
      synchronization or regulation of physiological and behavioral cycles needed for
      daily activity. How then do species that exhibit more flexible daily activity
      patterns, responses to ecological, environmental or life-history processes,
      regulate daily hormone profiles important to daily performance? This study
      examined the consequences of (1) nocturnal activity on diel profiles of melatonin
      and corticosterone and (2) the effects of experimentally increased acute
      melatonin levels on physiological and metabolic performance in the cane toad
      (Rhinella marinus). Unlike inactive captive toads that had a distinct nocturnal
      melatonin profile, nocturnally active toads sampled under field and captive
      conditions, exhibited decreased nocturnal melatonin profiles with no evidence for
      any phase shift. Nocturnal corticosterone levels were significantly higher in
      field active toads than captive toads. In toads with experimentally increased
      melatonin levels, plasma lactate and glucose responses following recovery post
      exercise were significantly different from control toads. However, exogenously
      increased melatonin did not affect resting metabolism in toads. These results
      suggest that toads could adjust daily hormone profiles to match nocturnal
      activity requirements, thereby avoiding performance costs induced by high
      nocturnal melatonin levels. The ability of toads to exhibit plasticity in daily
      hormone cycles, could have broad implications for how they and other animals
      utilize behavioral flexibility to optimize daily activities in response to
      natural and increasingly human mediated environmental variation. 

PMID- 25063396
TI  - Differential gene expression and metabolomic analyses of Brachypodium distachyon
      infected by deoxynivalenol producing and non-producing strains of Fusarium
      graminearum.
AB  - BACKGROUND: Fusarium Head Blight (FHB) caused primarily by Fusarium graminearum
      (Fg) is one of the major diseases of small-grain cereals including bread wheat.
      This disease both reduces yields and causes quality losses due to the production
      of deoxynivalenol (DON), the major type B trichothecene mycotoxin. DON has been
      described as a virulence factor enabling efficient colonization of spikes by the
      fungus in wheat, but its precise role during the infection process is still
      elusive. Brachypodium distachyon (Bd) is a model cereal species which has been
      shown to be susceptible to FHB. Here, a functional genomics approach was
      performed in order to characterize the responses of Bd to Fg infection using a
      global transcriptional and metabolomic profiling of B. distachyon plants infected
      by two strains of F. graminearum: a wild-type strain producing DON (Fgdon+) and a
      mutant strain impaired in the production of the mycotoxin (Fgdon-). RESULTS:
      Histological analysis of the interaction of the Bd21 ecotype with both Fg strains
      showed extensive fungal tissue colonization with the Fgdon+ strain while the
      florets infected with the Fgdon- strain exhibited a reduced hyphal extension and
      cell death on palea and lemma tissues. Fungal biomass was reduced in spikes
      inoculated with the Fgdon- strain as compared with the wild-type strain. The
      transcriptional analysis showed that jasmonate and ethylene-signalling pathways
      are induced upon infection, together with genes encoding putative detoxification
      and transport proteins, antioxidant functions as well as secondary metabolite
      pathways. In particular, our metabolite profiling analysis showed that tryptophan
      derived metabolites, tryptamine, serotonin, coumaroyl-serotonin and feruloyl
      serotonin, are more induced upon infection by the Fgdon+ strain than by the Fgdon
      strain. Serotonin was shown to exhibit a slight direct antimicrobial effect
      against Fg. CONCLUSION: Our results show that Bd exhibits defense hallmarks
      similar to those already identified in cereal crops. While the fungus uses DON as
      a virulence factor, the host plant preferentially induces detoxification and the
      phenylpropanoid and phenolamide pathways as resistance mechanisms. Together with
      its amenability in laboratory conditions, this makes Bd a very good model to
      study cereal resistance mechanisms towards the major disease FHB.

PMID- 25063399
TI  - Psychomotor skills in medical ultrasound imaging: an analysis of the core skill
      set.
AB  - Sonographers use psychomotor skills to perform medical ultrasound examinations.
      Psychomotor skills describe voluntary movements of the limb, joints, and muscles
      in response to sensory stimuli and are regulated by the motor neural cortex in
      the brain. We define a psychomotor skill in relation to medical ultrasound
      imaging as "the unique mental and motor activities required to execute a manual
      task safely and efficiently for each clinical situation." Skills in clinical
      ultrasound practice may be open or closed; most skills used in medical ultrasound
      imaging are open. Open skills are both complex and multidimensional. Visuomotor
      and visuospatial psychomotor skills are central components of medical ultrasound
      imaging. Both types of skills rely on learners having a visual exemplar or
      standard of performance with which to reference their skill performance and
      evaluate anatomic structures. These are imperative instructional design
      principles when teaching psychomotor skills. 

PMID- 25063398
TI  - Contrast echocardiography for assessment of left ventricular thrombi.
AB  - The diagnosis of intracardiac thrombi remains clinically relevant, with
      associated risks of systemic embolization and implications for antithrombotic
      management. Intravenously injected ultrasound contrast agents, composed of
      microbubbles smaller than red blood cells, have become established essential
      adjunctive tools for performance of state-of-the-art echocardiography, providing
      important information on cardiac structure and function. Despite advances in
      other imaging modalities, echocardiography remains the initial tool for diagnosis
      and risk stratification in patients predisposed to developing cardiac thrombi.
      Ultrasound contrast agents are approved for left ventricular (LV) opacification
      and endocardial border definition. Additionally, the use of contrast
      echocardiography facilitates LV thrombus detection by providing contrast
      opacification within the cardiac chambers to clearly show the "filling defect" of
      an intracardiac thrombus. Furthermore, contrast perfusion echocardiography can
      provide an assessment of the tissue characteristics of LV masses suspicious for
      intracardiac thrombi and, by differentiating an avascular thrombus from a tumor,
      results in improved diagnostic performance of echocardiography. This article
      presents a clinical vignette highlighting the sound judgment of using contrast
      echocardiography to aid in the diagnosis of LV thrombi and will review recent
      advances in imaging modalities for intracardiac thrombus detection. 

PMID- 25063400
TI  - A systematic review of amniotic fluid assessments in twin pregnancies.
AB  - The objectives of this systematic review were to examine the reproducibility of
      sonographic estimates of amniotic fluid volume (AFV) in twin pregnancies, compare
      the association of sonographic estimates of AFV with dye-determined AFV, and
      correlate AFV with antepartum, intrapartum, and perinatal outcomes in twin
      pregnancies. Studies were included if they were adequately powered and
      investigated antepartum, intrapartum, and/or perinatal adverse outcome parameters
      in twin gestations. Studies with comparable populations and exclusion criteria
      were merged into forest plots. Data comparing the accuracy of AFV assessment,
      correlation of AFV with gestational age, and adverse outcomes were tabulated.
      Five of the 6 studies investigating AFV by the amniotic fluid index as a function
      of gestational age reported data fitting a quadratic equation, with fluid volumes
      peaking at mid gestation and then declining. This trend was less pronounced when
      AFV was assessed by the single deepest pocket (2 of 4 studies reporting a
      quadratic fit). Polyhydramnios was associated with prematurity in 2 of 4 studies
      (1 amniotic fluid index and 1 single deepest pocket), and oligohydramnios was
      associated with prematurity in 1 single deepest pocket study. Stillbirth was the
      only intrapartum outcome reported in more than 1 study. Perinatal outcomes
      associated with polyhydramnios included neonatal death (P < .05 in 1 of 2
      studies), low Apgar scores (1 of 2 studies), neonatal intensive care unit
      admission (1 of 2 studies), and low birth weight (2 of 3 studies). 

PMID- 25063401
TI  - Use of fetal echocardiography for characterization of fetal cardiac structure in
      women with normal pregnancies and gestational diabetes mellitus.
AB  - OBJECTIVES: To assess fetal cardiac structure and function and to evaluate the
      efficacy of routine fetal echocardiography for detection of fetal cardiac
      abnormalities in women with normal pregnancies and those with gestational
      diabetes mellitus. METHODS: In this prospective study, we studied fetal cardiac
      structure and function in 294 uncomplicated singleton pregnancies and 302
      pregnancies complicated by gestational diabetes. Fetal echocardiography (2
      dimensional sonography and pulsed wave Doppler imaging) was used to assess
      functional parameters and to detect any cardiac structural abnormality. Data from
      clinical and echocardiographic evaluations of neonates at birth and 3 months were
      obtained to confirm the antenatal findings. RESULTS: The mean maternal age +/- SD
      was 28.9 +/- 5.0 years in the diabetes group and was comparable to that of women
      with normal pregnancies. The mean hemoglobin A1c value was 6.3%, and the mean
      body mass index was 28.0 kg/m(2). The systolic function as assessed by the
      ejection fraction increased significantly in the diabetes group compared to the
      normal pregnancy group independent of glycemic control (P < .001). The pulsed
      wave parameters (early diastolic peak flow velocity and early-to-late diastolic
      peak flow velocity ratio) were significantly different between the groups (P <
      .001). The interventricular septum and fetal ventricular wall thicknesses were
      significantly increased in the presence of gestational diabetes (P < .001). No
      major fetal cardiac structural anomaly was detected in either group. On follow-up
      after delivery, all neonates were assessed clinically and by transthoracic
      echocardiography to rule out congenital defects. CONCLUSIONS: In our study,
      significant increases in the interventricular septum and ventricular wall
      thicknesses were detected in the presence of gestational diabetes mellitus.
      Interestingly, none of the neonates of pregnant women with gestational diabetes
      were found to have echocardiographic evidence of congenital heart disease.

PMID- 25063402
TI  - Prospective study of intracranial translucency and the posterior brain in normal
      fetuses at the 11- to 13-week scan.
AB  - OBJECTIVES: To evaluate the ability of sonographers to prospectively identify
      intracranial translucency and posterior brain structures at 11 to 13 weeks and to
      evaluate measurement reproducibility of brain stem and brain stem-occipital bone
      diameters on stored images. METHODS: After specific training for intracranial
      translucency visualization, 10 nonphysician sonographers prospectively identified
      intracranial translucency at the 11- to 13-week scan, noting whether intracranial
      translucency was present, absent, or uncertain. If absent/uncertain, they
      documented the reason as spina bifida or an inadequate image (with reasons for
      the inadequate image). Measurements of brain stem and brain stem-occipital bone
      diameters were performed on stored images. Fifty randomly selected cases were
      reviewed for intraobserver and interobserver variability. RESULTS: In 313
      singleton pregnancies, the posterior brain including intracranial translucency
      was evaluated; 293 (93.6%) had known pregnancy outcomes. None had open spina
      bifida, but 7 had chromosomal or congenital abnormalities. In the remaining 286
      normal fetuses, intracranial translucency was seen in 275 (96%) and uncertain in
      11 (4%), due to inadequate images (top 3 reasons were fetal position [n = 8],
      obesity [n = 5], and retroverted uterus [n = 4]). Fetal position and gestational
      age were significantly associated with intracranial translucency visualization (P
      < .05). Intraobserver and interobserver agreement rates were moderate for
      measurements of brain stem diameter (intraclass correlation coefficients, 0.59
      and 0.57) and substantial for brain stem-occipital bone diameter (intraclass
      correlation coefficients, 0.76 and 0.61). Bland-Altman analysis revealed
      negligible intraobserver and interobserver differences in brain stem and brain
      stem-occipital bone diameter measurements. CONCLUSIONS: Intracranial translucency
      can be prospectively identified by trained sonographers in 96% of normal fetuses
      at 11 to 13 weeks. Measurements of brain stem and brain stem-occipital bone
      diameters are reproducible.

PMID- 25063403
TI  - Color Doppler Imaging Analysis of Retrobulbar Blood Flow Velocities in Diabetic
      Patients Without or With Retinopathy: A Meta-analysis.
AB  - OBJECTIVES: To analyze hemodynamic changes in retrobulbar blood vessels using
      color Doppler imaging in diabetic patients without or with retinopathy. METHODS:
      Pertinent publications were retrieved from 3 databases. Changes in peak systolic
      velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) of the
      ophthalmic artery, central retinal artery, and short posterior ciliary artery of
      diabetic eyes without or with retinopathy and healthy controls were evaluated by
      color Doppler imaging. Comparisons were conducted in 3 groups: group 1, no
      retinopathy versus control; group 2, retinopathy versus control; and group 3, no
      retinopathy versus retinopathy. RESULTS: In group 1, eyes without retinopathy had
      a significant increase in ophthalmic artery PSV (P = .002), with no heterogeneity
      (Pheterogeneity = 0.09; inconsistency index [I(2)] = 46%); however, significant
      reductions in central renal artery PSV and EDV were shown (P = .002; P = .007,
      respectively), with significant heterogeneity (Pheterogeneity < .00001; I(2) =
      85%; Pheterogeneity = .008, I(2) = 68%). A significant increase in ophthalmic
      artery RI (P = .02) was found in eyes without retinopathy, with heterogeneity
      (Pheterogeneity = .0009; I(2) = 74%). In group 2, central retinal artery PSV and
      EDV in eyes with retinopathy decreased significantly (P < 0.00001). Similar
      results were found for ophthalmic and short posterior ciliary artery EDVs (P=
      .0003; P< .00001). Ophthalmic artery RI was significantly higher in eyes with
      retinopathy than controls (P = .0008), with heterogeneity (Pheterogeneity <
      .00001; I(2) = 84%). In group 3, ophthalmic artery PSV was lower in eyes with
      retinopathy (P= .04) than eyes without, and central retinal artery PSV and EDV
      decreased significantly (P = .004; P < .00001) in eyes with retinopathy compared
      to eyes without. Differences in ophthalmic and central retinal artery RIs were
      also found in eyes with retinopathy (P = .05; P < .00001). CONCLUSIONS:
      Significant changes in retrobulbar blood flow were found in eyes without and with
      diabetic retinopathy, especially those with retinopathy.

PMID- 25063404
TI  - Increased epicardial adipose tissue thickness on transthoracic echocardiography
      in patients with Behcet disease.
AB  - OBJECTIVES: Owing to the fact that the potential frequency of endothelial
      dysfunction and early atherosclerosis might be higher in Behcet disease,
      characterized by acute and chronic inflammatory attacks, it may lead to
      impairment in flow-mediated dilatation and an increase in epicardial adipose
      tissue thickness. Therefore, we aimed to evaluate whether epicardial adipose
      tissue thickness and brachial artery flow-mediated dilatation as markers of early
      atherosclerosis and endothelial dysfunction were associated with Behcet disease.
      METHODS: Thirty-five patients with Behcet disease and 35 healthy volunteers were
      included in this study. Epicardial adipose tissue was identified as an anechoic
      space between epicardial layers on 2-dimensional images, and its thickness was
      measured on the free wall of the right ventricle. Right brachial artery flow
      mediated dilatation was assessed according to recent guidelines. RESULTS: Serum
      gamma-glutamyl transferase (GGT) levels and epicardial adipose tissue thickness
      were significantly higher (P = .001; P < .001 respectively), whereas flow
      mediated, endothelium-dependent dilatation was significantly lower in the Behcet
      disease group than controls (P < .001). There was a significant negative
      association between epicardial adipose tissue thickness and flow-mediated
      dilatation (P < .001). Epicardial adipose tissue thickness was also positively
      correlated with Behcet disease activity (P< .001), Behcet disease duration (P<
      .001), and waist circumference (P< .001). Flow-mediated dilatation was negatively
      correlated with GGT (P< .001), Behcet disease activity (P< .001), and age (P<
      .001). There was also a significant association between GGT and Behcet disease
      activity (P < .001). CONCLUSIONS: We found that epicardial adipose tissue
      thickness was significantly higher and flow-mediated dilatation was significantly
      lower in patients with Behcet disease than in controls. We suggest that
      identification of increased epicardial adipose tissue might aid in the diagnosis
      and treatment of possible coronary artery disease in patients with Behcet
      disease.

PMID- 25063405
TI  - Cardiac sonography by the neonatologist: clinical usefulness and educational
      perspective.
AB  - OBJECTIVES: Clinicians are increasingly using cardiac sonography in clinical
      practice. The objectives of this study were to assess the current state of
      clinician-performed cardiac sonography practice in the Australia-New Zealand
      region, with particular reference to the scope of clinical practice and type of
      training offered. METHODS: A prospective cross-sectional survey was conducted,
      and an electronic Web-based questionnaire was e-mailed to neonatologists and
      advanced trainees in the region. Information was collected on respondents
      (demographics, clinician-performed cardiac sonography experience, and opinions),
      equipment use, and training frameworks. Main outcome measures ascertained were
      clinical use and educational perspectives. RESULTS: The overall survey response
      rate was 64% (113 of 176). Eighty-five percent of respondents reported that
      clinician-performed cardiac sonography was performed in their units, most
      commonly to use the physiologic information obtained in conjunction with clinical
      information to refine decision making. The most common clinical indication was
      evaluation of a hemodynamically relevant ductus arteriosus. A dedicated
      echocardiographic machine was available to 80% of respondents. Most respondents
      reported "self-directed" learning as the most common method of training. More
      than 85% of respondents reported having access to either on-site or off-site
      pediatric cardiology services. CONCLUSIONS: Widespread availability and use of
      clinician-performed cardiac sonography in units across the Australia-New Zealand
      region was noted. The need for a structured training program was identified.

PMID- 25063406
TI  - Real-time sonographically guided percutaneous dilatational tracheostomy using a
      long-axis approach compared to the landmark technique.
AB  - OBJECTIVES: Sonographic evaluation of neck anatomy before performing percutaneous
      dilatational tracheostomy (PDT) has been shown to predict PDT success. In this
      study, we compared the real-time, long-axis, in-plane approach to the traditional
      bronchoscopically guided landmark technique. METHODS: Data were analyzed from a
      prospectively maintained PDT database at a university tertiary care medical
      intensive care unit. A convenience sample of adult patients requiring PDT for
      prolonged mechanical ventilation dependence was enrolled. Critical care fellows,
      under direct supervision of an attending intensivist, performed all PDTs.
      Tracheostomy performance from the sonographically guided and landmark techniques
      was compared. RESULTS: Twenty-three patients were enrolled: 11 in the sonography
      group and 12 in the landmark group. Initial midline introducer needle puncture
      was achieved in 72.7% in the sonography group compared to 8.3% in the landmark
      group (P< .001). The mean number of introducer needle punctures +/- SD was
      significantly lower in the sonography group compared to the landmark group (1.4
      +/- 0.7 versus 2.6 +/- 0.9; P < .001). The total tracheostomy time was 11.4 +/-
      4.2 minutes in the sonography group versus 15.3 +/- 6.8 minutes in the landmark
      group (P = .12). Sonography accurately predicted tracheal ring space insertion in
      90.9% of patients. Procedural complications did not differ significantly between
      the groups. CONCLUSIONS: Percutaneous dilatational tracheostomy under real-time
      sonographic guidance using a long-axis approach may increase the rate of midline
      punctures and decrease the number of needle punctures when compared to the
      landmark technique. Sonographic guidance can also help guide accurate and
      efficient placement of a tracheostomy tube into the desired tracheal ring space.

PMID- 25063407
TI  - Acoustic radiation force for noninvasive evaluation of corneal biomechanical
      changes induced by cross-linking therapy.
AB  - OBJECTIVES: To noninvasively measure changes in corneal biomechanical properties
      induced by ultraviolet-activated riboflavin cross-linking therapy using acoustic
      radiation force (ARF). METHODS: Cross-linking was performed on the right eyes of
      6 rabbits, with the left eyes serving as controls. Acoustic radiation force was
      used to assess corneal stiffness before treatment and weekly for 4 weeks after
      treatment. Acoustic power levels were within US Food and Drug Administration
      guidelines for ophthalmic safety. Strain, determined from ARF-induced
      displacement of the front and back surfaces of the cornea, was fit to the Kelvin
      Voigt model to determine the elastic modulus (E) and coefficient of viscosity
      (eta). The stiffness factor, the ratio of E after treatment to E before
      treatment, was calculated for treated and control eyes. At the end of 4 weeks, ex
      vivo thermal shrinkage temperature analysis was performed for comparison with in
      vivo stiffness measurements. One-way analysis of variance and Student t tests
      were performed to test for differences in E, eta, the stiffness factor, and
      corneal thickness. RESULTS: Biomechanical stiffening was immediately evident in
      cross-linking-treated corneas. At 4 weeks after treatment, treated corneas were
      1.3 times stiffer and showed significant changes in E (P= .006) and eta (P=
      .007), with no significant effect in controls. Corneal thickness increased
      immediately after treatment but did not differ significantly from the
      pretreatment value at 4 weeks. CONCLUSIONS: Our findings demonstrate a
      statistically significant increase in stiffness in cross-linking-treated rabbit
      corneas based on in vivo axial stress/strain measurements obtained using ARF. The
      capacity to noninvasively monitor corneal stiffness offers the potential for
      clinical monitoring of cross-linking therapy.

PMID- 25063409
TI  - Freehand elastography for determination of breast cancer size: comparison with B
      mode sonography and histopathologic measurement.
AB  - OBJECTIVES: Elastography assesses the strain of soft tissues and is used to
      enhance diagnostic accuracy in evaluating breast tumors, but minimal data exist
      on its ability to accurately assess tumor size. This study was performed to
      assess the preoperative accuracy of measuring the size of biopsyproven breast
      cancer lesions with elastography and conventional B-mode sonography compared with
      the reference standard size measured by histopathologic examination. METHODS:
      Elastography and conventional B-mode sonography were performed on 69 women with
      histologically proven breast cancer, and tumor sizes on both modalities were
      recorded. These measurements were compared with the final pathologic size, which
      was used as the reference standard. The sizes and differences between
      sonographic, elastographic, and pathologic measurements were statistically
      tested, and an analysis of equivalence to the reference standard was performed
      using Bland-Altman plots. RESULTS: There was a significant difference between
      sizes on elastography and pathologic examination, with elastography
      overestimating the tumor size (P = .0187). Sonography slightly underestimated the
      tumor size, but this finding was not significant (P = .36). Bland-Altman plots
      confirmed that sonography but not elastography was an acceptable standard
      compared with the pathologic size. CONCLUSIONS: Breast elastography but not B
      mode sonography overestimates the size of breast tumors compared with the final
      pathologic size.

PMID- 25063408
TI  - Volumetric contrast-enhanced ultrasound imaging of renal perfusion.
AB  - OBJECTIVES: To determine whether volumetric contrast-enhanced ultrasound (US)
      imaging has the potential to monitor changes in renal perfusion after vascular
      injury. METHODS: Volumetric contrast-enhanced US uses a series of planar image
      acquisitions, capturing the nonlinear second harmonic signal from microbubble
      contrast agents flowing in the vasculature. Tissue perfusion parameters (peak
      intensity [IPK], time to peak intensity [TPK], wash-in rate [WIR], and area under
      the curve [AUC]) were derived from time-intensity curve data collected during in
      vitro flow phantom studies and in vivo animal studies of healthy and injured
      kidneys. For the flow phantom studies, either the contrast agent concentration
      was held constant (10 MUL/L) with varying volumetric flow rates (10, 20, and 30
      mL/min), or the flow rate was held constant (30 mL/min) with varying contrast
      agent concentrations (5, 10, and 20 MUL/L). Animal studies used healthy rats or
      those that underwent renal ischemia-reperfusion injury. Renal studies were
      performed with healthy rats while the transducer angle was varied for each
      volumetric contrast-enhanced US image acquisition (reference or 0 degrees , 45
      degrees , and 90 degrees ) to determine whether repeated renal perfusion measures
      were isotropic and independent of transducer position. Blood serum biomarkers and
      immunohistology were used to confirm acute kidney injury. RESULTS: Flow phantom
      results revealed a linear relationship between microbubble concentrations
      injected into the flow system and the IPK, WIR, and AUC (R(2) > 0.56; P < .005).
      Furthermore, there was a linear relationship between volume flow rate changes and
      the TPK, WIR, and AUC (R(2) > 0.77; P < .005). No significant difference was
      found between the transducer angle during data acquisition and any of the
      perfusion measures (P > .60). After induction of renal ischemia-reperfusion
      injury in the rat animal model (n = 4), volumetric contrast-enhanced US imaging
      of the injured kidney revealed an initial reduction in renal perfusion compared
      to control animals, followed by progressive recovery of vascular function.
      CONCLUSIONS: Volumetric contrast-enhanced US-based renal perfusion imaging may
      prove clinically feasible for detecting and monitoring acute kidney injury.

PMID- 25063410
TI  - Focal fatty sparing usually does not arise in preexisting nonalcoholic diffuse
      homogeneous fatty liver.
AB  - OBJECTIVES: The purpose of this study was to investigate whether focal fatty
      sparing can arise in preexisting nonalcoholic diffuse homogeneous fatty liver and
      its clinical implications. METHODS: This prospective study consisted of 2 parts.
      In the first part, 8598 people (5202 men and 3396 women; mean age +/- SD, 43.4 +/
      28.3 years; range, 18-82 years) were consecutively evaluated with sonography for
      abnormal liver findings; in the second part, participants with diffuse
      homogeneous fatty liver were followed over approximately 3 years. Sonographic
      findings of the participants in the first year and findings of the participants
      with diffuse homogeneous fatty liver in the first and third years were analyzed.
      RESULTS: In the first part, 778 of 8598 participants (9.05%) were found to have
      fatty liver, including 752 cases of nonalcoholic diffuse fatty liver (8.75%) and
      26 cases of alcoholic fatty liver (0.30%). Of the 752 cases of nonalcoholic
      diffuse fatty liver, 301 participants had nonalcoholic diffuse homogeneous fatty
      liver, and 68 (9.04%) had focal fatty sparing. In the second part, the 301
      participants with nonalcoholic diffuse homogeneous fatty liver (205 men and 96
      women; mean age, 39.6 +/- 10.4 years; range, 18-60 years) were followed. In the
      third year, 2 cases of fatty liver (0.67%) had resolved, 2 cases (0.67%) had
      inflammatory pseudotumors, and no focal fatty sparing was found (P < .001).
      CONCLUSIONS: The findings of this study suggest that focal fatty sparing usually
      does not arise in preexisting nonalcoholic diffuse homogeneous fatty liver, and a
      newly emerging abnormality is more likely a true lesion.

PMID- 25063411
TI  - Use of acoustic radiation force impulse elastography to diagnose acute
      pancreatitis at hospital admission: comparison with sonography and computed
      tomography.
AB  - OBJECTIVES: To compare the diagnostic success rate of acoustic radiation force
      impulse (ARFI) elastography with those of sonography and computed tomography (CT)
      for acute pancreatitis at hospital admission. METHODS: B-mode sonography and ARFI
      elastography were performed on 88 patients with symptoms of acute pancreatitis
      and 50 healthy control participants who were admitted to our hospital between
      February 2013 and July 2013. Acute pancreatitis was verified in the 88 patients
      based on clinical and laboratory findings. Computed tomography was performed on
      41 patients, and the CT results from these patients were compared with those of
      ARFI elastography. The appearances of the pancreases of the patients were
      classified into 6 groups using visual color encodings obtained with ARFI
      elastography. The elasticity values of pancreatic head, body, and tail regions
      were evaluated with Virtual Touch imaging and Virtual Touch tissue quantification
      (Siemens Medical Solutions, Mountain View, CA). The success rates of sonography,
      CT, and ARFI elastography for diagnosing acute pancreatitis at hospital admission
      were compared. RESULTS: Forty-six of the 88 patients had a diagnosis of
      pancreatitis by B-mode sonography; pancreatitis was diagnosed in all patients by
      ARFI elastography; and 10 of 41 patients could not be diagnosed by CT. The
      sensitivity and specificity of Virtual Touch tissue quantification were 100% and
      98%, respectively, when a cutoff value of 1.63 m/s was used. The control group
      had color scores of 1 or 2, whereas all patients with pancreatitis had color
      scores of 3 to 6 on color scale evaluation with Virtual Touch imaging.
      CONCLUSIONS: Acoustic radiation force impulse elastography is a rapid, radiation
      free, and noninvasive tool for diagnosis of acute pancreatitis at initial
      hospital admission, with a higher success rate for diagnosis of acute
      pancreatitis than the grayscale sonography and CT.

PMID- 25063412
TI  - Sonographically guided distal biceps tendon injections: techniques and
      validation.
AB  - OBJECTIVES: The primary purpose of this investigation was to describe and
      validate sonographically guided techniques for distal biceps
      peritendinous/intratendinous injections using a cadaveric model. METHODS: A
      single experienced operator completed 18 sonographically guided distal biceps
      peritendinous injections and 15 sonographically guided distal biceps
      intratendinous injections in 18 unembalmed cadaveric elbow specimens (11 male and
      7 female; age, 53-100 years; body mass index, 19.4-42.2 kg/m(2)). Four different
      peritendinous approaches were used to inject 3 mL of diluted yellow latex: (1)
      anterior/superficial, (2) posterior/superficial, (3) posterior/deep/short-axis
      (to the distal biceps tendon), and (4) posterior/deep/long-axis (to the distal
      biceps tendon). Three different intratendinous approaches were used to inject 1
      mL of diluted blue latex: (1) anterior, (2) anterior/pronator window, and (3)
      posterior. The feasibility of all 7 injections was assessed by the operator in
      all specimens, and execution difficulty was recorded after each injection.
      Specimens were subsequently dissected to assess injectate placement. RESULTS: All
      18 peritendinous distal biceps tendon injections accurately placed latex around
      the tendon without injecting into the tendon proper. All posterior/superficial
      peritendinous injections delivered injectate to the ulnar side of the tendon. All
      posterior/deep peritendinous injections delivered injectate to the radial side of
      the tendon, with the long-axis approach being technically easier than the short
      axis approach. Anterior/superficial peritendinous injections delivered injectate
      predominantly to the anterior side of the tendon and resulted in 1 brachial
      artery injury. All but 1 of 15 distal biceps intratendinous injections (93%)
      accurately placed injectate into the tendon proper, with 1 of 5 anterior
      injections delivering injectate primarily deep to the paratenon. The posterior
      intratendinous approach was technically the easiest. No intratendinous injection
      resulted in neurovascular injury. CONCLUSIONS: Sonographically guided distal
      biceps peritendinous/intratendinous injections are feasible and therefore may
      play a role in the management of patients presenting with distal biceps
      tendinopathy/bursopathy.

PMID- 25063413
TI  - Sonography of the lateral antebrachial cutaneous nerve with magnetic resonance
      imaging and anatomic correlation.
AB  - OBJECTIVES: Abnormalities of the lateral antebrachial cutaneous nerve (LABCN) are
      associated with antecubital elbow conditions, such as distal biceps brachii
      tendon tears and traumatic cephalic vein phlebotomy. These can lead to lateral
      forearm, elbow, and wrist symptoms that can mimic other disease processes. The
      purpose of this study was to characterize the sonographic appearance of the LABCN
      using cadaveric dissection and retrospective analysis of sonographic examinations
      of symptomatic patients with magnetic resonance imaging correlation. METHODS: For
      the first part of this study, a cadaveric elbow specimen was examined, and
      sonography was performed after dissection to identify the LABCN. Subsequently, 26
      elbows in 13 patients with LABCN abnormalities were identified with sonography
      and retrospectively evaluated to characterize the appearance of the LABCN in both
      symptomatic and asymptomatic elbows. RESULTS: The symptomatic LABCNs showed
      fusiform enlargement, increased echogenicity, and loss of the normal fascicular
      echo texture. The mean cross-sectional area of the symptomatic nerves was 12.0
      mm(2) (range, 6.1-17.2 mm(2)), with a maximum thickness of 3.5 mm (range, 2.3-5.9
      mm), compared to 3.3 mm(2) (range, 1.9-5.2 mm(2)), with a maximum thickness of
      1.3 mm (range, 0.9-2.2 mm), in the contralateral normal elbows. CONCLUSIONS: The
      close proximity of the LABCN to the distal biceps tendon and the cephalic vein
      makes it vulnerable to compression and injury in the setting of distal biceps
      tendon tears and traumatic phlebotomy, which may cause nerve enlargement and
      increased echogenicity. Awareness of the location and appearance of the LABCN on
      sonography is important for determining potential causes of lateral elbow and
      forearm pain.

PMID- 25063414
TI  - Sonographic assessment of the medial ulnar collateral ligament distal ulnar
      attachment.
AB  - OBJECTIVES: The purpose of this study was to determine whether the long distal
      attachment of the medial ulnar collateral ligament (MUCL) can be delineated on
      sonography. METHODS: We used 12 fresh-frozen cadaveric elbows for this study. We
      performed sonography of the elbow using a coronal-equivalent long-axis view of
      the MUCL. All sonographic examinations and measurements were performed by a board
      certified, fellowship-trained musculoskeletal radiologist. Measurements were
      performed from the anteroinferior aspect of the medial epicondyle to the sublime
      tubercle and then from the sublime tubercle to the terminal fibers of the MUCL
      long ulnar attachment. We then measured the length of the MUCL from its
      attachment at the medial epicondyle of the humerus to the sublime tubercle and
      then from the sublime tubercle to the distal extent of its terminal fibers at the
      ulnar attachment with digital calipers. RESULTS: On sonography, the average
      length of the MUCL from its humeral attachment to the sublime tubercle
      (transarticular) was 19.6 mm. The average length of the ulnar attachment was 27.9
      mm. The MUCL was thickest (mediolateral dimension) at its humeral attachment and
      tapered as it coursed distally along the ulnar attachment. The MUCL was clearly
      identified on sonography and in all anatomic specimens. On gross measurement, the
      average lengths of the transarticular portion of the MUCL and its ulnar footprint
      were 21.5 and 30.2 mm, respectively. CONCLUSIONS: We have successfully shown that
      the distal ulnar attachment of the MUCL can be visualized on high-resolution
      sonography. This preliminary work provides a framework for developing protocols
      for diagnosis of injuries to the distal ulnar collateral ligament.

PMID- 25063415
TI  - Types of sublingual gland herniation observed during sonography of plunging
      ranulas.
AB  - OBJECTIVES: Plunging ranulas have been shown to have a common trio of mylohyoid
      defects, sublingual gland herniation, and submandibular space fluid collections.
      The herniated sublingual gland may be susceptible to subclinical trauma. The
      purpose of this study was to investigate the frequency of occurrence of various
      types of active sublingual gland herniation observed during diagnostic
      sonographic studies. METHODS: Sonographic findings of sublingual gland herniation
      from 76 patients with a total of 80 plunging ranulas are presented. All
      sublingual gland herniations, including those on the contralateral side, were
      documented at the time of the examinations and reviewed later. The sonographic
      appearances of active sublingual gland herniation were given the names "slide,"
      "wobble," "mushroom," and "retrusion" to reflect the observed movement. RESULTS:
      Mylohyoid defects were found in 98% of plunging ranulas. The different types of
      sublingual gland herniation observed were as follows: slide in 77.8%, wobble in
      11.1%, mushroom in 9.7%, and retrusion in 1.4%. The unaffected contralateral side
      showed a wobble in 44.8% of cases and slide in 8.9%. CONCLUSIONS: Sublingual
      gland herniation through mylohyoid defects is easily missed if one is unaware.
      Prior knowledge of the various types of sublingual gland herniation and their
      frequencies of occurrence are very helpful during diagnostic sonographic
      examinations.

PMID- 25063416
TI  - Clinical application of a modern high-definition head-mounted display in
      sonography.
AB  - Because of the remarkably improved image quality and wearability of modern head
      mounted displays, a monitoring system using a head-mounted display rather than a
      fixed-site monitor for sonographic scanning has the potential to improve the
      diagnostic performance and lessen the examiner's physical burden during a
      sonographic examination. In a preclinical setting, 2 head-mounted displays, the
      HMZ-T2 (Sony Corporation, Tokyo, Japan) and the Wrap1200 (Vuzix Corporation,
      Rochester, NY), were found to be applicable to sonography. In a clinical setting,
      the feasibility of the HMZ-T2 was shown by its good image quality and acceptable
      wearability. This modern device is appropriate for clinical use in sonography. 

PMID- 25063417
TI  - Radial artery pseudoaneurysm: a simplified treatment method.
AB  - A radial artery pseudoaneurysm represents a rare, potentially catastrophic
      complication of arterial cannulation that has been reported after cardiac
      catheterization. Treatment options are limited to chemical, mechanical, and
      combined approaches to obliterate the radial artery pseudoaneurysm and tract.
      Manual compression protocols using the TR Band (Terumo Medical Corporation,
      Somerset, NJ) have been variable and anecdotal, without objective measurements of
      adequate compression, making this technique prone to failure. In this report, we
      present an efficient, safe, and noninvasive management protocol using a pulse
      oximeter and the TR Band for treatment of radial artery pseudoaneurysms that is
      cost-effective and efficient and ensures correction without occlusion of the
      radial artery. 

PMID- 25063418
TI  - Clinical and radiologic features of neuroendocrine breast carcinomas.
AB  - Neuroendocrine breast carcinoma is a rare and distinct type of breast carcinoma,
      with morphologic features similar to those of pulmonary and gastrointestinal
      tract neuroendocrine tumors. More than 50% of cells express neuroendocrine
      markers. We documented the clinical and radiologic features of 11 patients with
      histologically confirmed neuroendocrine breast carcinomas. Clinical
      manifestations included nipple discharge (6 patients) and palpable masses (5
      patients). Lesions were mainly oval or irregular on mammography (n = 8),
      sonography (n = 11), and magnetic resonance imaging (n = 9). Understanding the
      clinical and radiologic features of neuroendocrine breast carcinoma will
      facilitate the differential diagnosis. 

PMID- 25063419
TI  - Sonographic appearances of desmoid tumors.
AB  - The medical records of 16 patients (9 female and 7 male; age range, 5-66 years)
      with 24 lesions that had a histologic diagnosis of desmoid tumors were reviewed
      at our institution. Six cases were extra-abdominal, 4 intra-abdominal, and 6 in
      the abdominal wall. Lesions ranged from 1.5 to 18.0 cm in diameter (mean, 6.8
      cm). All lesions were solid masses, which appeared hypoechoic, isoechoic, or
      hyperechoic with homogeneous or heterogeneous echogenicity. Posterior acoustic
      enhancement was seen in 18 lesions. No lesions showed central necrosis. Most
      lesions had substantial flow and high resistive index values (>0.70). Sonography
      can show a desmoid tumor's site, size, contour, margin, echogenicity,
      homogeneity, vascularity, and resistive index value in detail. 

PMID- 25063420
TI  - Source diversity among journals cited in Science Times.
AB  - A content analysis of The New York Times' Science Times section from 1998 to 2012
      found evidence of increased source diversity in use of scientific journals as
      news sources. Science Times increased the frequency at which it cited journals,
      the number of different journals that it cited, and the number of disciplines
      represented by cited journals. The results suggest that online availability of a
      wide array of scientific journals has changed sourcing behaviors. 

PMID- 25063421
TI  - Attitudes to genetically modified food over time: How trust in organizations and
      the media cycle predict support.
AB  - This research examined public opinion toward genetically modified plants and
      animals for food, and how trust in organizations and media coverage explained
      attitudes toward these organisms. Nationally representative samples (N=8821) over
      10 years showed Australians were less positive toward genetically modified
      animals compared to genetically modified plants for food, especially in years
      where media coverage was high. Structural equation modeling found that positive
      attitudes toward different genetically modified organisms for food were
      significantly associated with higher trust in scientists and regulators (e.g.
      governments), and with lower trust in watchdogs (e.g. environmental movement).
      Public trust in scientists and watchdogs was a stronger predictor of attitudes
      toward the use of genetically modified plants for food than animals, but only
      when media coverage was low. Results are discussed regarding the moral
      acceptability of genetically modified organisms for food, the media's role in
      shaping public opinion, and the role public trust in organizations has on
      attitudes toward genetically modified organisms.

PMID- 25063422
TI  - An fNIRS investigation of associative recognition in the prefrontal cortex with a
      rapid event-related design.
AB  - BACKGROUND: Functional near-infrared spectroscopy (fNIRS) measures hemodynamic
      changes at the cortical level. The use of fNIRS is growing in popularity for
      studying cognitive neuroscience in which event-related designs are widely used
      with functional magnetic resonance imaging (fMRI). However, the applicability of
      event-related designs with fNIRS has not been fully understood. Therefore, the
      present study employed fNIRS with a rapid-presentation event-related design for
      investigating prefrontal cortical activity during complex associative
      recognition. NEW METHOD: Participants studied a list of word pairs and were later
      given an associative recognition test. Throughout the experiment, each event was
      presented rapidly (~4s). Data were sorted based on accuracy of associative memory
      judgments and analyzed using the general linear model (GLM) with an event-related
      design. RESULTS: During retrieval, significant increases in oxygenated hemoglobin
      concentrations were observed in dorsolateral and ventrolateral prefrontal regions
      for successful associative recognition. When comparing retrieval to encoding,
      significant increases in oxygenated hemoglobin concentrations were also observed
      in dorsolateral prefrontal cortex. COMPARISON WITH EXISTING METHOD: The current
      fNIRS results corroborate previous fMRI findings that have demonstrated the
      involvement of dorsolateral and ventrolateral prefrontal cortex in associative
      recognition. Therefore, the present study validates versatile use of fNIRS with a
      rapid-presentation event-related design in the investigation of neural mechanisms
      of associative memory. CONCLUSION: The findings of this study provide evidence
      that fNIRS can be a viable research method for investigating complex cognitive
      processes commonly of interest in cognitive neuroscience. Taken together, these
      results demonstrate that fNIRS can be a cost-effective and accessible
      experimental tool for cognitive neuroscience.

PMID- 25063423
TI  - Appraisal of the effect of brain impregnation duration on neuronal staining and
      morphology in a modified Golgi-Cox method.
AB  - BACKGROUND: Golgi-Cox staining method is considered as one of the best
      neurohistological and fascinating staining techniques to reveal the
      cytoarchitecture of the brain. Requirement of longer time (more than a month),
      laborious section processing steps, requirement of sophisticated equipment's and
      costly ready to use kits limits extensive use of this technique. NEW METHOD: The
      need for a modified staining technique is to overcome some of these hurdles. Here
      we describe a modification of Golgi-Cox staining involving reduced impregnation
      time (7 days), omitting tissue dehydration steps, and alterations in section
      processing steps. Different impregnation duration (7 days, 14 days, 1 month, 6
      months and 10 months) effects on optimized staining of dorsal hippocampus and
      basolateral amygdala were investigated. RESULTS: Modified Golgi-Cox staining
      method was found to be effective in staining rat hippocampus and amygdala.
      Impregnation for 7 days, 14 days and 1 month resulted in giving good results and
      they were comparable. However, artifacts were slightly elevated with 6 months
      group but not extensively. Impregnation for 10 months negatively affected the
      staining process. COMPARISON WITH EXISTING METHOD(S): Compared to existing
      methods the current method was found to be cost effective, fast, reliable and can
      be executed in labs where infrastructure is limited. CONCLUSIONS: Current
      modification considerably benefitted in obtaining better results (good clarity
      and lesser artifact) in a short time. Longer impregnated brain sections were
      found to be unsuitable for morphometric evaluation due to more stain
      precipitation and artifact. The modified technique can be used to study cellular
      architecture in other brain regions.

PMID- 25063424
TI  - Prediction of membranous nephropathy recurrence after transplantation by
      monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a
      case series of 15 patients.
AB  - BACKGROUND: The predictive value of anti-M-type phospholipase A2 receptor
      (PLA2R1) autoantibodies for membranous nephropathy (MN) recurrence after renal
      transplantation remains controversial. METHODS: Our aim was to monitor anti
      PLA2R1 IgG4 activity using a sensitive enzyme-linked immunosorbent assay in 15
      kidney transplant recipients with MN, and to test the correlation between
      antibody titres and MN recurrence. RESULTS: Five patients never exhibited anti
      PLA2R1 antibodies, and one of them relapsed. Ten patients (67%) had IgG4 anti
      PLA2R1 antibodies at the time of transplantation and during follow-up. The
      presence of IgG4 anti-PLA2R1 antibodies at the time of kidney transplantation
      does not imply MN recurrence (P = 0.600, n = 15). However, a positive IgG4 anti
      PLA2R1 activity during follow-up (>Month 6) was a significant risk factor for MN
      relapse (P = 0.0048, n = 10). Indeed, four patients had persistent IgG4 anti
      PLA2R1 activity after transplantation and relapsed. Among them, one was
      successfully treated with rituximab. Another had persistently high IgG4 anti
      PLA2R1 activity and exhibited a histological relapse but no proteinuria while on
      treatment with renin-angiotensin system inhibitors. In contrast, the six other
      patients who did not relapse exhibited a decrease of their IgG4 anti-PLA2R1
      activity following transplant immunosuppression, including two with proteinuria
      due to biopsy-proven differential diagnoses. A weak transplant immunosuppressive
      regimen was also a risk factor of MN recurrence (P = 0.0048, n = 10). Indeed, the
      six patients who received both an induction therapy and a combined treatment with
      calcineurin inhibitors/mycophenolate exhibited a decrease of IgG4 anti-PLA2R1
      activity and did not relapse, while the four patients who did not receive this
      strong immunosuppressive treatment association had persistently high IgG4 anti
      PLA2R1 activity and relapsed. CONCLUSION: The monitoring of IgG4 anti-PLA2R1
      titres during follow-up helps to predict MN recurrence, and a strong
      immunosuppressive treatment of anti-PLA2R1 positive patients may prevent
      recurrence.

PMID- 25063425
TI  - Renal histologic changes and the outcome in patients with diabetic nephropathy.
AB  - BACKGROUND: The progression of diabetic nephropathy (DN) is frequently determined
      by clinical parameters; however, the predictive value of histologic lesions
      remains largely unknown. Our aim was to evaluate the relationship between
      histologic changes and renal outcome in patients with type 2 diabetes mellitus
      (T2DM). METHODS: A total of 396 patients with T2DM and biopsy-proven DN who
      received follow-up for at least 1 year were recruited. The severity of different
      histologic lesions was assessed using the pathologic classification established
      by the Renal Pathology Society. Renal outcomes were defined by progression to end
      stage renal disease and doubling of serum creatinine. The influence of histologic
      findings on renal outcomes was assessed using univariate and multivariate Cox
      regression. RESULTS: A univariate Cox regression showed that the severity of
      glomerular and interstitial lesions had a significant impact on renal outcomes (P
      < 0.001). Scores of vascular lesions demonstrated no association with renal
      outcomes (P > 0.05). A multivariate COX analysis demonstrated that the glomerular
      classes and scores of interstitial fibrosis and tubular atrophy were
      significantly associated with renal outcomes when adjusting for baseline
      proteinuria, mean arterial pressure and estimated glomerular filtration rate (P <
      0.05). The glomerular and interstitial lesions correlated significantly among
      each other. However, in several patients, the severity of interstitial lesions
      did not correlate with glomerular lesions. CONCLUSION: These findings indicated
      that the severity of glomerular and interstitial lesions were significantly
      associated with renal outcomes in patients with DN, whereas the vascular indexes
      did not have any impact on renal outcomes.

PMID- 25063426
TI  - Large genetic animal models of Huntington's Disease.
AB  - The dominant nature of the Huntington's disease gene mutation has allowed genetic
      models to be developed in multiple species, with the mutation causing an abnormal
      neurological phenotype in all animals in which it is expressed. Many different
      rodent models have been generated. The most widely used of these, the transgenic
      R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and
      has a rapidly progressive and fatal neurological phenotype with many relevant
      pathological changes. Nevertheless, their rapid decline has been frequently
      questioned in the context of a disease that takes years to manifest in humans,
      and strenuous efforts have been made to make rodent models that are genetically
      more 'relevant' to the human condition, including full length huntingtin gene
      transgenic and knock-in mice. While there is no doubt that we have learned, and
      continue to learn much from rodent models, their usefulness is limited by two
      species constraints. First, the brains of rodents differ significantly from
      humans in both their small size and their neuroanatomical organization. Second,
      rodents have much shorter lifespans than humans. Here, we review new approaches
      taken to these challenges in the development of models of Huntington's disease in
      large brained, long-lived animals. We discuss the need for such models, and how
      they might be used to fill specific niches in preclinical Huntington's disease
      research, particularly in testing gene-based therapeutics. We discuss the
      advantages and disadvantages of animals in which the prodromal period of disease
      extends over a long time span. We suggest that there is considerable 'value
      added' for large animal models in preclinical Huntington's disease research. 

PMID- 25063427
TI  - Longitudinal neuroimaging biomarkers in Huntington's Disease.
AB  - Identifying markers able to characterise the progression of Huntington's Disease
      (HD) is of great importance to the HD research community, as such markers may
      provide valuable outcome measures in future clinical trials. Neuroimaging
      measures are obvious candidates because of their clear relevance to the
      neuropathology of the disease. Many also show improved precision and sensitivity
      compared with standard functional scales. This review summarizes findings from
      the wealth of longitudinal imaging studies in the literature, focusing on the
      most widely available imaging modalities: structural MRI (volumetric and
      diffusion imaging), functional MRI and PET. We discuss the longitudinal
      sensitivity, reproducibility and feasibility of each imaging modality for use in
      clinical trials. 

PMID- 25063428
TI  - Finding the striatum in sheep: use of a multi-modal guided approach for
      convection enhanced delivery.
AB  - Our goal is delivery of a long-term treatment for Huntington's disease. We
      administer intracerebrally in sheep adeno-associated virus (AAV) to establish
      optimal safety, spread and neuronal uptake of AAV based therapeutics. Sheep have
      large gyrencephalic brains and offer the opportunity to study a transgenic
      Huntington's disease model. However, lack of a relevant brain stereotactic atlas
      and the difficulty of skull fixation make conventional stereotaxy unreliable. We
      describe a multi-modal image-guidance technique to achieve accurate placement of
      therapeutics into the sheep striatum. 

PMID- 25063429
TI  - A transgenic minipig model of Huntington's Disease.
AB  - BACKGROUND: Some promising treatments for Huntington's disease (HD) may require
      pre-clinical testing in large animals. Minipig is a suitable species because of
      its large gyrencephalic brain and long lifespan. OBJECTIVE: To generate HD
      transgenic (TgHD) minipigs encoding huntingtin (HTT)1-548 under the control of
      human HTT promoter. METHODS: Transgenesis was achieved by lentiviral infection of
      porcine embryos. PCR assessment of gene transfer, observations of behavior, and
      postmortem biochemical and immunohistochemical studies were conducted. RESULTS:
      One copy of the human HTT transgene encoding 124 glutamines integrated into
      chromosome 1 q24-q25 and successful germ line transmission occurred through
      successive generations (F0, F1, F2 and F3 generations). No developmental or gross
      motor deficits were noted up to 40 months of age. Mutant HTT mRNA and protein
      fragment were detected in brain and peripheral tissues. No aggregate formation in
      brain up to 16 months was seen by AGERA and filter retardation or by
      immunostaining. DARPP32 labeling in WT and TgHD minipig neostriatum was patchy.
      Analysis of 16 month old sibling pairs showed reduced intensity of DARPP32
      immunoreactivity in neostriatal TgHD neurons compared to those of WT. Compared to
      WT, TgHD boars by one year had reduced fertility and fewer spermatozoa per
      ejaculate. In vitro analysis revealed a significant decline in the number of WT
      minipig oocytes penetrated by TgHD spermatozoa. CONCLUSIONS: The findings
      demonstrate successful establishment of a transgenic model of HD in minipig that
      should be valuable for testing long term safety of HD therapeutics. The emergence
      of HD-like phenotypes in the TgHD minipigs will require more study.

PMID- 25063430
TI  - NGF rescues hippocampal cholinergic neuronal markers, restores neurogenesis, and
      improves the spatial working memory in a mouse model of Huntington's Disease.
AB  - BACKGROUND: Recent studies in Huntington's disease (HD) mouse models and patients
      suggest that hippocampal neurons and their cholinergic afferents are involved in
      the cognitive deficits seen in the disease. Nerve growth factor (NGF) is an
      essential regulator of cholinergic neuronal survival and neurotransmission.
      OBJECTIVE: We asked whether NGF might be involved in HD and if intra
      cerebroventricular infusion of NGF can rescue hippocampal cholinergic neuronal
      markers, restore neurogenesis, and improve the spatial working memory in R6/1
      mouse model of HD. METHODS: We quantified NGF protein level by enzyme-linked
      immunosorbent assay (ELISA), intracerebroventricularly infused NGF, assessed
      cholinergic neuronal markers by Western blotting and quantitative RT-PCR,
      evaluated neurogenesis by immunohistochemistry, and studied spatial working
      memory using radial maze. RESULTS: By quantifying NGF protein in the hippocampus
      of the R6/1 mice at different ages, we found progressive decreases in NGF protein
      levels. We then increased NGF levels in the R6/1 mice through intra
      cerebroventricular infusion. We observed elevations of the cholinergic
      neurochemical markers vesicular acetylcholine transporter (VAChT) and choline
      acetyltransferase (ChAT) in the hippocampus and in the septal region, which
      contain the cell bodies of basal forebrain cholinergic neurons (BFCNs), but not
      in the striatum that harbors cholinergic interneurons. Finally, we found that NGF
      infusion also restored hippocampal neurogenesis and improved spatial working
      memory. CONCLUSIONS: Our results suggest that intracerebral injections of NGF
      might be a valuable therapy against cognitive symptoms in HD and should be
      further studied in HD animal models and patients.

PMID- 25063431
TI  - Preliminary analysis of Huntington's Disease in South Korea.
AB  - BACKGROUND: There have been epidemiological studies of Huntington's disease (HD)
      in various populations and nations. Only a few studies describing clinical
      characteristics have been reported in Asia. OBJECTIVE: To conduct preliminary
      analyses of demographic, clinical and genetic characteristics of HD in South
      Korea. METHODS: From 1994 to 2011, thirty six subjects were diagnosed as HD in
      Seoul National University Hospital. Demographic, clinical and genetic data were
      carefully analyzed in all subjects. RESULTS: Mean age of onset was 46.5 +/- 12.7
      years and mean expanded CAG repeat size was 45.4 +/- 4.7. Twenty-eight subjects
      (80%) had a family history of HD. Chorea was the most frequent symptom at first
      visit (89%). Proportion of cognitive decline (36%) and psychiatric symptom (28%)
      at first visit were lower than proportion of previous reports. A negative
      correlation (Pearson correlation coefficient -0.757, p = 0.001) was found between
      expanded CAG repeat size and age of onset. Seven subjects without family history
      of HD had higher mean age of onset (54.0 +/- 8.1) and smaller expanded CAG repeat
      size (42.4 +/- 2.7). Cognitive problems at first visit of subjects without family
      history were more prominent than those with family history (86% vs. 25%).
      CONCLUSIONS: This study is the first demographic, clinical and genetic analyses
      in South Korea. These results will be helpful to stimulate more large-scale
      research in South Korea and other Asian nations.

PMID- 25063432
TI  - Proteomic analysis of the human brain in Huntington's Disease indicates
      pathogenesis by molecular processes linked to other neurodegenerative diseases
      and to type-2 diabetes.
AB  - BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder in which
      the aetiological defect is inherited or spontaneous mutation in the HTT gene,
      which alters the structure of the corresponding huntingtin protein and initiates
      a pathogenetic cascade that ultimately leads to or causes dementia. OBJECTIVE:
      Here our main objective was to elucidate further the pathogenic processes that
      underlie neurodegeneration in HD. METHODS: By using two-dimensional gel
      electrophoresis we performed a proteomic case-control study of two brain regions
      in post-mortem human tissue from seven well-characterized HD patients and eight
      matched controls. RESULTS: In the middle frontal gyrus we identified twenty-two
      differentially-expressed proteins whereas by contrast in visual cortex only seven
      were altered. Twenty of these proteins have not to our knowledge been associated
      with the pathogenesis of HD before although all functional families implicated
      have previously been linked to other neurodegenerative diseases. Most of the
      proteins identified play roles in cell stress responses, apoptosis, metabolic
      regulation linked to type-2 diabetes, the ubiquitin-proteasome system, or protein
      trafficking/endocytosis. CONCLUSIONS: We propose that HTT mutations lead to or
      cause functional impairment of these pathways and that simultaneous restoration
      of their functions by targeted pharmacotherapy could ameliorate the signs and
      symptoms of HD. These studies provide a unique illustration of the interlinked
      disease processes that underpin/contribute to the pathogenesis of
      neurodegeneration in a genetically-mediated disorder of protein structure, and
      provide a signpost towards the design of new therapeutic interventions.

PMID- 25063433
TI  - Pharmacological upregulation of PGC1alpha in oligodendrocytes: implications for
      Huntington's Disease.
AB  - The coactivator PGC1alpha plays a role in the transcriptional regulation of
      energy metabolism and its deficiency has been implicated in abnormalities of
      myelination and oligodendrocyte differentiation in Huntington's disease (HD). In
      an effort to activate PGC1alpha in oligodendrocytes, we found that overexpression
      of SIRT1 or treatment with resveratrol (RSV) and SRT1720 upregulated PGC1alpha
      expression and increased oligodendrocyte differentiation. Interestingly, in
      oligodendrocytes expressing mutant huntingtin, SRT1720 but not RSV was able to
      restore PGC1alpha expression and the differentiation. These results suggest that
      pharmacological activation of PGC1alpha in oligodendrocytes by SRT1720 may
      provide a therapeutic opportunity for correction of deficient myelination in HD. 

PMID- 25063434
TI  - A critical evaluation of inflammatory markers in Huntington's Disease plasma.
AB  - BACKGROUND: Huntington's Disease (HD) is a hereditary, progressive
      neurodegenerative disorder characterised by both neurological and systemic
      symptoms. In HD, immune changes can be observed before the onset of overt
      clinical features raising the possibility that inflammatory markers in plasma
      could be used to track disease progression. It has previously been demonstrated
      that a widespread, progressive innate immune response is detectable in plasma
      throughout the course of HD. OBJECTIVE: The aim of the present study was to
      investigate the potential of several components of inflammation and innate
      immunity as plasma biomarkers in HD. METHODS: We utilised antibody-based
      detection technologies as well as mass spectrometric quantification, multiple
      reaction monitoring (MRM-MS). RESULTS: Levels of several markers previously
      described as altered in HD, such as clusterin, complement component 4, complement
      component 9 and alpha-2 macroglobulin did not differ between healthy controls and
      HD subjects as measured by Luminex, ELISA or MRM-MS. C-reactive protein was
      decreased in early HD, while the other immune markers tested were unaltered.
      CONCLUSIONS: Although only C-reactive protein was found to be reduced in early
      HD, some of the inflammatory markers measured correlated with clinical measures.

PMID- 25063435
TI  - Catheter last, fistula not-so-first.

PMID- 25063436
TI  - Vascular access choice in incident hemodialysis patients: a decision analysis.
AB  - Hemodialysis vascular access recommendations promote arteriovenous (AV) fistulas
      first; however, it may not be the best approach for all hemodialysis patients,
      because likelihood of successful fistula placement, procedure-related and
      subsequent costs, and patient survival modify the optimal access choice. We
      performed a decision analysis evaluating AV fistula, AV graft, and central venous
      catheter (CVC) strategies for patients initiating hemodialysis with a CVC, a
      scenario occurring in over 70% of United States dialysis patients. A decision
      tree model was constructed to reflect progression from hemodialysis initiation.
      Patients were classified into one of three vascular access choices: maintain CVC,
      attempt fistula, or attempt graft. We explicitly modeled probabilities of primary
      and secondary patency for each access type, with success modified by age, sex,
      and diabetes. Access-specific mortality was incorporated using preexisting cohort
      data, including terms for age, sex, and diabetes. Costs were ascertained from the
      2010 USRDS report and Medicare for procedure costs. An AV fistula attempt
      strategy was found to be superior to AV grafts and CVCs in regard to mortality
      and cost for the majority of patient characteristic combinations, especially
      younger men without diabetes. Women with diabetes and elderly men with diabetes
      had similar outcomes, regardless of access type. Overall, the advantages of an AV
      fistula attempt strategy lessened considerably among older patients, particularly
      women with diabetes, reflecting the effect of lower AV fistula success rates and
      lower life expectancy. These results suggest that vascular access-related
      outcomes may be optimized by considering individual patient characteristics. 

PMID- 25063437
TI  - Quantifying the health benefits of chronic disease prevention: a fresh approach
      using cardiovascular disease as an example.
AB  - Current methods of determining the proportion of people who benefit from a
      preventive intervention and the years of life gained can underestimate the former
      and overestimate the latter. We describe how to overcome these errors, using two
      examples relating to the prevention of myocardial infarction (MI) and stroke, one
      using a specified polypill daily from age 50 and another reducing salt intake in
      the population. Standard life table analysis was used to calculate the person
      years of life gained without an MI or stroke, based on estimates of the incidence
      of these disorders in England and Wales. The proportion of individuals who
      benefit was taken as everyone who would, without treatment, have an MI or stroke
      (holistic model), rather than limiting the benefit to the proportion calculated
      from the relative risk reduction (reductionist model), as is current practice.
      Under the holistic model, 33% of people who take the polypill from age 50
      benefit, gaining, on average, 8 years of life without an MI or stroke (19% and 14
      years under the reductionist model). Estimates for reducing salt intake by 6
      g/day are 33% and 2.8 years respectively under the holistic model (6% and 16
      years under the reductionist model). In the prevention of disorders such as
      stroke by reducing exposure to causal factors such as blood pressure, the use of
      a holistic model corrects the underestimation of the proportion of people who
      benefit and the overestimation of their years of life gained associated with
      current methods.

PMID- 25063438
TI  - Dual-targeted proteins tend to be more evolutionarily conserved.
AB  - In eukaryotic cells, identical proteins can be located in more than a single
      subcellular compartment, a phenomenon termed dual targeting. We hypothesized that
      dual-targeted proteins should be more evolutionary conserved than exclusive
      mitochondrial proteins, due to separate selective pressures administered by the
      different compartments to maintain the functions associated with the protein
      sequences. We employed codon usage bias, propensity for gene loss, phylogenetic
      relationships, conservation analysis at the DNA level, and gene expression, to
      test our hypothesis. Our findings indicate that, indeed, dual-targeted proteins
      are significantly more conserved than their exclusively targeted counterparts. We
      then used this trait of gene conservation, together with previously identified
      traits of dual-targeted proteins (such as protein net charge and mitochondrial
      targeting sequence strength) to 1) create, for the first time (due to addition of
      conservation parameters), a tool for the prediction of dual-targeted
      mitochondrial proteins based on protein and mRNA sequences, and 2) show that
      molecular mechanisms involving one versus two translation products are not
      correlated with specific dual-targeting parameters. Finally, we discuss what
      evolutionary pressure maintains protein dual targeting in eukaryotes and deduce,
      as we initially hypothesized, that it is the discrete functions of these proteins
      in the different subcellular compartments, regardless of their dual-targeting
      mechanism. 

PMID- 25063439
TI  - An experimentally informed evolutionary model improves phylogenetic fit to
      divergent lactamase homologs.
AB  - Phylogenetic analyses of molecular data require a quantitative model for how
      sequences evolve. Traditionally, the details of the site-specific selection that
      governs sequence evolution are not known a priori, making it challenging to
      create evolutionary models that adequately capture the heterogeneity of selection
      at different sites. However, recent advances in high-throughput experiments have
      made it possible to quantify the effects of all single mutations on gene
      function. I have previously shown that such high-throughput experiments can be
      combined with knowledge of underlying mutation rates to create a parameter-free
      evolutionary model that describes the phylogeny of influenza nucleoprotein far
      better than commonly used existing models. Here, I extend this work by showing
      that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW,
      Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene's
      fitness landscape. Mol Biol Evol. 31:1581-1592) can be combined with a few
      mutation rate parameters to create an evolutionary model that describes beta
      lactamase phylogenies much better than most common existing models. This
      experimentally informed evolutionary model is superior even for homologs that are
      substantially diverged (about 35% divergence at the protein level) from the TEM-1
      parent that was the subject of the experimental study. These results suggest that
      experimental measurements can inform phylogenetic evolutionary models that are
      applicable to homologs that span a substantial range of sequence divergence. 

PMID- 25063440
TI  - Automated structural comparisons clarify the phylogeny of the right-hand-shaped
      polymerases.
AB  - Polymerases are essential for life, being responsible for replication,
      transcription, and the repair of nucleic acid molecules. Those that share a right
      hand-shaped fold and catalytic site structurally similar to the DNA polymerase I
      of Escherichia coli may catalyze RNA- or DNA-dependent RNA polymerization,
      reverse transcription, or DNA replication in eukarya, archaea, bacteria, and
      their viruses. We have applied novel computational methods for structure-based
      clustering and phylogenetic analyses of this functionally diverse polymerase
      superfamily, which currently comprises six families. We identified a structural
      core common to all right-handed polymerases, composed of 57 amino acid residues,
      harboring two positionally and chemically conserved residues, the catalytic
      aspartates. The structural conservation within each of the six families is
      considerable, for example, the structural core shared by family Y DNA polymerases
      covers over 90% of the polymerase domain of the Sulfolobus solfataricus Dpo4. Our
      phylogenetic analyses propose an early separation of RNA-dependent polymerases
      that use primers from those that are primer-independent. Furthermore, the
      exchange of polymerase genes between viruses and their hosts is evident. Because
      of this horizontal gene transfer, the phylogeny of polymerases does not always
      reflect the evolutionary history of the corresponding organisms. 

PMID- 25063441
TI  - Functional evolution of cardiac microRNAs in heart development and functions.
AB  - MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that regulate
      gene expression either by degrading target mRNAs or by suppressing protein
      translation. miRNAs have been found to be involved in many biological processes,
      such as development, differentiation, and growth. However, the evolution of miRNA
      regulatory functions and networks has not been well studied. In this study, we
      conducted a cross-species analysis to study the evolution of cardiac miRNAs and
      their regulatory functions and networks. We found that conserved cardiac miRNA
      target genes have maintained highly conserved cardiac functions. Additionally,
      most of cardiac miRNA target genes in human with annotations of cardiac functions
      evolved from the corresponding homologous targets, which are also involved in
      heart development-related functions. On the basis of these results, we
      investigated the functional evolution of cardiac miRNAs and presented a
      functional evolutionary map. From this map, we identified the evolutionary time
      at which the cardiac miRNAs became involved in heart development or function and
      found that the biological processes of heart development evolved earlier than
      those of heart functions, for example, heart contraction/relaxation or cardiac
      hypertrophy. Our study of the evolution of the cardiac miRNA regulatory networks
      revealed the emergence of new regulatory functional branches during evolution.
      Furthermore, we discovered that early evolved cardiac miRNA target genes tend to
      participate in the early stages of heart development. This study sheds light on
      the evolution of developmental features of genes regulated by cardiac miRNAs. 

PMID- 25063442
TI  - Perturbation of iron homeostasis promotes the evolution of antibiotic resistance.
AB  - Evolution of antibiotic resistance in microbes is frequently achieved by
      acquisition of spontaneous mutations during antimicrobial therapy. Here, we
      demonstrate that inactivation of a central transcriptional regulator of iron
      homeostasis (Fur) facilitates laboratory evolution of ciprofloxacin resistance in
      Escherichia coli. To decipher the underlying molecular mechanisms, we first
      performed a global transcriptome analysis and demonstrated that the set of genes
      regulated by Fur changes substantially in response to antibiotic treatment. We
      hypothesized that the impact of Fur on evolvability under antibiotic pressure is
      due to the elevated intracellular concentration of free iron and the consequent
      enhancement of oxidative damage-induced mutagenesis. In agreement with
      expectations, overexpression of iron storage proteins, inhibition of iron
      transport, or anaerobic conditions drastically suppressed the evolution of
      resistance, whereas inhibition of the SOS response-mediated mutagenesis had only
      a minor effect. Finally, we provide evidence that a cell permeable iron chelator
      inhibits the evolution of resistance. In sum, our work revealed the central role
      of iron metabolism in the de novo evolution of antibiotic resistance, a pattern
      that could influence the development of novel antimicrobial strategies. 

PMID- 25063444
TI  - Interleukin 22 protects colorectal cancer cells from chemotherapy by activating
      the STAT3 pathway and inducing autocrine expression of interleukin 8.
AB  - Resistance to chemotherapy is the major cause of colorectal cancer (CRC)
      treatment failure. The cytokine IL-22, which is produced by T cells and NK cells,
      is associated with tumorigenesis and tumor progression in cancers. However, the
      role of IL-22 in chemoresistance has not been investigated. We found that IL-22
      levels in tumor tissues and peripheral blood were associated with chemoresistance
      and indicate poor prognosis for patients who received FOLFOX chemotherapy. In CRC
      cells, IL-22 was able to attenuate the cytotoxic and apoptosis-inducing effects
      of 5-FU and OXA by activating the STAT3 pathway and subsequently increasing the
      expression of anti-apoptotic genes. In addition, IL-22 conferred resistance to 5
      FU and OXA by inducing IL-8 autocrine expression through STAT3 activation. Our
      findings identify IL-22 as a novel chemoresistance cytokine and may be a useful
      prognostic biomarker for CRC patients receiving FOLFOX chemotherapy. 

PMID- 25063445
TI  - Successful stem cell transplantation in a child with chronic granulomatous
      disease associated with contiguous gene deletion syndrome and complicated by
      macrophage activation syndrome.

PMID- 25063446
TI  - Multi-enzyme digestion FASP and the 'Total Protein Approach'-based absolute
      quantification of the Escherichia coli proteome.
AB  - We describe a proteomic approach combining the multi-enzyme digestion FASP-sample
      processing strategy and the 'Total Protein Approach' applied to absolute
      quantification of proteins in Escherichia coli. Consecutive digestion of whole
      cell lysates with LysC and trypsin allowed the generation of two populations of
      peptides at a yield of 76%. Subsequent two 4-hour LC-MS/MS analyses allowed the
      identification of 19,000 unique peptides per sample. Notably, only 1.2 and 2.4%
      of the identified peptides were found to be incompletely cleaved by the LysC and
      trypsin, respectively. The analysis resulted in the identification of 2200
      proteins per sample. We show high reproducibility of the approach, allowing the
      accurate estimation of cellular protein concentrations. Quantitative analysis of
      the DNA content per sample enabled the calculation of the protein content per
      bacterial cell and, as a result, estimation of protein copy numbers. The accuracy
      of these estimations was confirmed by analyzing protein complexes with known
      subunit stoichiometry and cellular abundances. In stationary culture, a single
      bacterium contains about 6500 copies of ribosomes, 300 molecules of RNA
      polymerase and 10 DNA polymerase assembles. The here presented experimental and
      computational workflow offers an easy way to analyze proteomes quantitatively.
      BIOLOGICAL SIGNIFICANCE: We demonstrate a proteomic workflow for in-depth
      analysis of small proteomes with minimal fractionation extent and mass
      spectrometry measuring time. For the first time we provide the quantitative
      picture of the Escherichia coli proteome at protein copy number.

PMID- 25063443
TI  - Early evolution of the eukaryotic Ca2+ signaling machinery: conservation of the
      CatSper channel complex.
AB  - Calcium signaling is one of the most extensively employed signal transduction
      mechanisms in life. As life evolved into increasingly complex organisms, Ca(2+)
      acquired more extensive and varied functions. Here, we compare genes encoding
      proteins that govern Ca(2+) entry and exit across cells or organelles within
      organisms of early eukaryotic evolution into fungi, plants, and animals. Recent
      phylogenomics analyses reveal a complex Ca(2+) signaling machinery in the
      apusozoan protist Thecamonas trahens, a putative unicellular progenitor of
      Opisthokonta. We compare T. trahens Ca(2+) signaling to that in a marine bikont
      protist, Aurantiochytrium limacinum, and demonstrate the conservation of key
      Ca(2+) signaling molecules in the basally diverging alga Cyanophora paradoxa.
      Particularly, our findings reveal the conservation of the CatSper channel complex
      in Au. limacinum and C. paradoxa, suggesting that the CatSper complex likely
      originated from an ancestral Ca(2+) signaling machinery at the root of early
      eukaryotic evolution prior to the unikont/bikont split. 

PMID- 25063447
TI  - [Usefulness of the measurement of lactic acid in cerebrospinal fluid].

PMID- 25063448
TI  - Linezolid and vancomycin-resistant Enterococcus faecium peritonitis in a child
      after liver transplantation.

PMID- 25063449
TI  - Safety and efficacy of antiretroviral therapy in perinatally HIV-1 infected
      patients following transition to an adult HIV-care hospital with virological
      failure in Buenos Aires, Argentina.

PMID- 25063450
TI  - Treatment of selected pharmaceuticals by ferrate(VI): performance, kinetic
      studies and identification of oxidation products.
AB  - The performance of ferrate(VI) in treating sulfamethoxazole (SMX), diclofenac
      (DCF), carbamazepine (CBZ) and bezafibrate (BZF) in test solutions containing the
      four compounds was investigated. A series of jar-test experiments was performed
      on a bench-scale at pH 6-9 and at a ferrate(VI) dose of 1-5 mg Fe/L. The results
      suggested that ferrate(VI) can effectively remove SMX, DCF and CBZ from the test
      solutions, with greater than 80% removal under optimum conditions. However, the
      removal efficiency of BZF was very low, less than 25% under the studied
      conditions. Increasing the dose of ferrate(VI) improved the treatment
      performance, while the influence of solution pH on ferrate(VI) performance varied
      among the different target compounds. Ferrate(VI) demonstrated the highest
      reactivity with SMX at pH 8 and pH 9 (20  degrees C), with apparent second-order
      rate constants of 360+/-17 M(-1) s(-1) and 1.26+/-0.02 M(-1) s(-1), respectively.
      However, BZF showed the lowest removal by ferrate(VI) with the smallest rate
      constants (less than 0.5 M(-1) s(-1)) at pH 8 and pH 9. Furthermore, a number of
      oxidation products (OPs) of SMX, DCF and CBZ during ferrate(VI) oxidation were
      detected by liquid chromatography and mass spectrometry (LC-MS), and their
      degradation pathways were tentatively proposed. No OPs of BZF were detected
      during ferrate(VI) oxidation.

PMID- 25063451
TI  - The nuclear hormone receptor family member NR5A2 controls aspects of multipotent
      progenitor cell formation and acinar differentiation during pancreatic
      organogenesis.
AB  - The orphan nuclear receptor NR5A2 is necessary for the stem-like properties of
      the epiblast of the pre-gastrulation embryo and for cellular and physiological
      homeostasis of endoderm-derived organs postnatally. Using conditional gene
      inactivation, we show that Nr5a2 also plays crucial regulatory roles during
      organogenesis. During the formation of the pancreas, Nr5a2 is necessary for the
      expansion of the nascent pancreatic epithelium, for the subsequent formation of
      the multipotent progenitor cell (MPC) population that gives rise to pre-acinar
      cells and bipotent cells with ductal and islet endocrine potential, and for the
      formation and differentiation of acinar cells. At birth, the NR5A2-deficient
      pancreas has defects in all three epithelial tissues: a partial loss of endocrine
      cells, a disrupted ductal tree and a >90% deficit of acini. The acinar defects
      are due to a combination of fewer MPCs, deficient allocation of those MPCs to pre
      acinar fate, disruption of acinar morphogenesis and incomplete acinar cell
      differentiation. NR5A2 controls these developmental processes directly as well as
      through regulatory interactions with other pancreatic transcriptional regulators,
      including PTF1A, MYC, GATA4, FOXA2, RBPJL and MIST1 (BHLHA15). In particular,
      Nr5a2 and Ptf1a establish mutually reinforcing regulatory interactions and
      collaborate to control developmentally regulated pancreatic genes by binding to
      shared transcriptional regulatory regions. At the final stage of acinar cell
      development, the absence of NR5A2 affects the expression of Ptf1a and its acinar
      specific partner Rbpjl, so that the few acinar cells that form do not complete
      differentiation. Nr5a2 controls several temporally distinct stages of pancreatic
      development that involve regulatory mechanisms relevant to pancreatic oncogenesis
      and the maintenance of the exocrine phenotype. 

PMID- 25063452
TI  - Major transcriptome re-organisation and abrupt changes in signalling, cell cycle
      and chromatin regulation at neural differentiation in vivo.
AB  - Here, we exploit the spatial separation of temporal events of neural
      differentiation in the elongating chick body axis to provide the first analysis
      of transcriptome change in progressively more differentiated neural cell
      populations in vivo. Microarray data, validated against direct RNA sequencing,
      identified: (1) a gene cohort characteristic of the multi-potent stem zone
      epiblast, which contains neuro-mesodermal progenitors that progressively generate
      the spinal cord; (2) a major transcriptome re-organisation as cells then adopt a
      neural fate; and (3) increasing diversity as neural patterning and neuron
      production begin. Focussing on the transition from multi-potent to neural state
      cells, we capture changes in major signalling pathways, uncover novel Wnt and
      Notch signalling dynamics, and implicate new pathways (mevalonate pathway/steroid
      biogenesis and TGFbeta). This analysis further predicts changes in cellular
      processes, cell cycle, RNA-processing and protein turnover as cells acquire
      neural fate. We show that these changes are conserved across species and provide
      biological evidence for reduced proteasome efficiency and a novel lengthening of
      S phase. This latter step may provide time for epigenetic events to mediate large
      scale transcriptome re-organisation; consistent with this, we uncover
      simultaneous downregulation of major chromatin modifiers as the neural programme
      is established. We further demonstrate that transcription of one such gene,
      HDAC1, is dependent on FGF signalling, making a novel link between signals that
      control neural differentiation and transcription of a core regulator of chromatin
      organisation. Our work implicates new signalling pathways and dynamics, cellular
      processes and epigenetic modifiers in neural differentiation in vivo, identifying
      multiple new potential cellular and molecular mechanisms that direct
      differentiation. 

PMID- 25063454
TI  - Auxin represses stomatal development in dark-grown seedlings via Aux/IAA
      proteins.
AB  - Stomatal development is tightly regulated through internal and external factors
      that are integrated by a complex signalling network. Light represents an external
      factor that strongly promotes stomata formation. Here, we show that auxin
      resistant aux/iaa mutants, e.g. axr3-1, exhibit a de-repression of stomata
      differentiation in dark-grown seedlings. The higher stomatal index in dark-grown
      axr3-1 mutants when compared with the wild type is due to increased cell division
      in the stomatal lineage. Excessive stomata in dark-grown seedlings were also
      observed in mutants defective in auxin biosynthesis or auxin perception and in
      seedlings treated with the polar auxin transport inhibitor NPA. Consistent with
      these findings, exogenous auxin repressed stomata formation in light-grown
      seedlings. Taken together, these results indicate that auxin is a negative
      regulator of stomatal development in dark-grown seedlings. Epistasis analysis
      revealed that axr3-1 acts genetically upstream of the bHLH transcription factors
      SPCH, MUTE and FAMA, as well as the YDA MAP kinase cascade, but in parallel with
      the repressor of photomorphogenesis COP1 and the receptor-like protein TMM. The
      effect of exogenous auxin required the ER family of leucine-rich repeat receptor
      like kinases, suggesting that auxin acts at least in part through the ER family.
      Expression of axr3-1 in the stomatal lineage was insufficient to alter the
      stomatal index, implying that cell-cell communication is necessary to mediate the
      effect of auxin. In summary, our results show that auxin signalling contributes
      to the suppression of stomatal differentiation observed in dark-grown seedlings. 

PMID- 25063453
TI  - Visualisation of chicken macrophages using transgenic reporter genes: insights
      into the development of the avian macrophage lineage.
AB  - We have generated the first transgenic chickens in which reporter genes are
      expressed in a specific immune cell lineage, based upon control elements of the
      colony stimulating factor 1 receptor (CSF1R) locus. The Fms intronic regulatory
      element (FIRE) within CSF1R is shown to be highly conserved in amniotes and
      absolutely required for myeloid-restricted expression of fluorescent reporter
      genes. As in mammals, CSF1R-reporter genes were specifically expressed at high
      levels in cells of the macrophage lineage and at a much lower level in
      granulocytes. The cell lineage specificity of reporter gene expression was
      confirmed by demonstration of coincident expression with the endogenous CSF1R
      protein. In transgenic birds, expression of the reporter gene provided a defined
      marker for macrophage-lineage cells, identifying the earliest stages in the yolk
      sac, throughout embryonic development and in all adult tissues. The reporter
      genes permit detailed and dynamic visualisation of embryonic chicken macrophages.
      Chicken embryonic macrophages are not recruited to incisional wounds, but are
      able to recognise and phagocytose microbial antigens. 

PMID- 25063455
TI  - Kinesin-II recruits Armadillo and Dishevelled for Wingless signaling in
      Drosophila.
AB  - Wingless (Wg)/Wnt signaling is fundamental in metazoan development. Armadillo
      (Arm)/beta-catenin and Dishevelled (Dsh) are key components of Wnt signal
      transduction. Recent studies suggest that intracellular trafficking of Wnt
      signaling components is important, but underlying mechanisms are not well known.
      Here, we show that Klp64D, the Drosophila homolog of Kif3A kinesin II subunit, is
      required for Wg signaling by regulating Arm during wing development. Mutations in
      klp64D or RNAi cause wing notching and loss of Wg target gene expression. The
      wing notching phenotype by Klp64D knockdown is suppressed by activated Arm but
      not by Dsh, suggesting that Klp64D is required for Arm function. Furthermore,
      klp64D and arm mutants show synergistic genetic interaction. Consistent with this
      genetic interaction, Klp64D directly binds to the Arm repeat domain of Arm and
      can recruit Dsh in the presence of Arm. Overexpression of Klp64D mutated in the
      motor domain causes dominant wing notching, indicating the importance of the
      motor activity. Klp64D shows subcellular localization to intracellular vesicles
      overlapping with Arm and Dsh. In klp64D mutants, Arm is abnormally accumulated in
      vesicular structures including Golgi, suggesting that intracellular trafficking
      of Arm is affected. Human KIF3A can also bind beta-catenin and rescue klp64D RNAi
      phenotypes. Taken together, we propose that Klp64D is essential for Wg signaling
      by trafficking of Arm via the formation of a conserved complex with Arm. 

PMID- 25063456
TI  - Leading and trailing cells cooperate in collective migration of the zebrafish
      posterior lateral line primordium.
AB  - Collective migration of cells in the zebrafish posterior lateral line primordium
      (PLLp) along a path defined by Cxcl12a expression depends on Cxcr4b receptors in
      leading cells and on Cxcr7b in trailing cells. Cxcr7b-mediated degradation of
      Cxcl12a by trailing cells generates a local gradient of Cxcl12a that guides PLLp
      migration. Agent-based computer models were built to explore how a polarized
      response to Cxcl12a, mediated by Cxcr4b in leading cells and prevented by Cxcr7b
      in trailing cells, determines unidirectional migration of the PLLp. These
      chemokine signaling-based models effectively recapitulate many behaviors of the
      PLLp and provide potential explanations for the characteristic behaviors that
      emerge when the PLLp is severed by laser to generate leading and trailing
      fragments. As predicted by our models, the bilateral stretching of the leading
      fragment is lost when chemokine signaling is blocked in the PLLp. However,
      movement of the trailing fragment toward the leading cells, which was also
      thought to be chemokine dependent, persists. This suggested that a chemokine
      independent mechanism, not accounted for in our models, is responsible for this
      behavior. Further investigation of trailing cell behavior shows that their
      movement toward leading cells depends on FGF signaling and it can be re-oriented
      by exogenous FGF sources. Together, our observations reveal the simple yet
      elegant manner in which leading and trailing cells coordinate migration; while
      leading cells steer PLLp migration by following chemokine cues, cells further
      back play follow-the-leader as they migrate toward FGFs produced by leading
      cells. 

PMID- 25063458
TI  - ECM stiffness regulates glial migration in Drosophila and mammalian glioma
      models.
AB  - Cell migration is an important feature of glial cells. Here, we used the
      Drosophila eye disc to decipher the molecular network controlling glial
      migration. We stimulated glial motility by pan-glial PDGF receptor (PVR)
      activation and identified several genes acting downstream of PVR. Drosophila lox
      is a non-essential gene encoding a secreted protein that stiffens the
      extracellular matrix (ECM). Glial-specific knockdown of Integrin results in ECM
      softening. Moreover, we show that lox expression is regulated by Integrin
      signaling and vice versa, suggesting that a positive-feedback loop ensures a
      rigid ECM in the vicinity of migrating cells. The general implication of this
      model was tested in a mammalian glioma model, where a Lox-specific inhibitor
      unraveled a clear impact of ECM rigidity in glioma cell migration. 

PMID- 25063459
TI  - The future burden of obesity-related diseases in the 53 WHO European-Region
      countries and the impact of effective interventions: a modelling study.
AB  - OBJECTIVE: Non-communicable diseases (NCDs) are the biggest cause of death in
      Europe putting an unsustainable burden on already struggling health systems.
      Increases in obesity are a major cause of NCDs. This paper projects the future
      burden of coronary heart disease (CHD), stroke, type 2 diabetes and seven cancers
      by 2030 in 53 WHO European Region countries based on current and past body mass
      index (BMI) trends. It also tests the impact of obesity interventions on the
      future disease burden. SETTING AND PARTICIPANTS: Secondary data analysis of
      country-specific epidemiological data using a microsimulation modelling process.
      INTERVENTIONS: The effect of three hypothetical scenarios on the future burden of
      disease in 2030 was tested: baseline scenario, BMI trends go unchecked;
      intervention 1, population BMI decreases by 1%; intervention 2, BMI decreases by
      5%. PRIMARY AND SECONDARY OUTCOME MEASURES: Quantifying the future burden of
      major NCDs and the impact of interventions on this future disease burden.
      RESULTS: By 2030 in the whole of the European region, the prevalence of diabetes,
      CHD and stroke and cancers was projected to reach an average of 3990, 4672 and
      2046 cases/100 000, respectively. The highest prevalence of diabetes was
      predicted in Slovakia (10 870), CHD and stroke-in Greece (11 292) and cancers-in
      Finland (5615 cases/100 000). A 5% fall in population BMI was projected to
      significantly reduce cumulative incidence of diseases. The largest reduction in
      diabetes and CHD and stroke was observed in Slovakia (3054 and 3369 cases/100
      000, respectively), and in cancers was predicted in Germany (331/100 000).
      CONCLUSIONS: Modelling future disease trends is a useful tool for policymakers so
      that they can allocate resources effectively and implement policies to prevent
      NCDs. Future research will allow real policy interventions to be tested; however,
      better surveillance data on NCDs and their risk factors are essential for
      research and policy.

PMID- 25063457
TI  - Visualization of the Drosophila dKeap1-CncC interaction on chromatin illumines
      cooperative, xenobiotic-specific gene activation.
AB  - Interactions among transcription factors control their physiological functions by
      regulating their binding specificities and transcriptional activities. We
      implement a strategy to visualize directly the genomic loci that are bound by
      multi-protein complexes in single cells in Drosophila. This method is based on
      bimolecular fluorescence complementation (BiFC) analysis of protein interactions
      on polytene chromosomes. Drosophila Keap1 (dKeap1)-CncC complexes localized to
      the nucleus and bound chromatin loci that were not bound preferentially by dKeap1
      or CncC when they were expressed separately. dKeap1 and CncC binding at these
      loci was enhanced by phenobarbital, but not by tert-butylhydroquinone (tBHQ) or
      paraquat. Endogenous dKeap1 and CncC activated transcription of the Jheh (Jheh1,
      Jheh2, Jheh3) and dKeap1 genes at these loci, whereas CncC alone activated other
      xenobiotic response genes. Ectopic dKeap1 expression increased CncC binding at
      the Jheh and dKeap1 gene loci and activated their transcription, whereas dKeap1
      inhibited CncC binding at other xenobiotic response gene loci and suppressed
      their transcription. The combinatorial chromatin-binding specificities and
      transcriptional activities of dKeap1-CncC complexes mediated the selective
      activation of different sets of genes by different xenobiotic compounds, in part
      through feed-forward activation of dKeap1 transcription. 

PMID- 25063460
TI  - Determinants of patient delay in doctor consultation in head and neck cancers
      (Protocol DEREDIA).
AB  - INTRODUCTION: Reducing the time between the onset of the first symptoms of cancer
      and the first consultation with a doctor (patient delay) is essential to improve
      the vital prognosis and quality of life of patients. Longer patient delay is
      linked to the already known sociodemographic, socioeconomic, socioeducational,
      sociocultural and socioprofessional factors. However, recent data suggest that
      some sociocognitive and emotional determinants may explain patient delay from a
      complementary point of view. The main objective of this study is to assess
      whether, in head and neck cancer, patient delay is linked to these sociocognitive
      and emotional factors, in addition to previously known factors. METHODS AND
      ANALYSIS: We intend to include in this study 400 patients with a not yet treated
      head and neck cancer diagnosed in one of six health centres in the North of
      France region. The main evaluation criterion is 'patient delay'. Sociocognitive,
      emotional, medical, sociodemographic, socioeconomic, educational, professional
      and geographic factors will be assessed by means of (1) a case report form, (2) a
      questionnaire completed by the clinical research associate together with the
      patient, (3) a questionnaire completed by the patient and (4) a recorded
      semidirective interview of the patient by a psychologist (for 80 patients only).
      The collected data will be analysed to underline the differences between patients
      who consulted a doctor earlier versus those who consulted later. ETHICS: The
      study has obtained all the relevant authorisations for the protection of patients
      enrolled in clinical trials (CCTIRS, CCP, CNIL), does not involve products
      mentioned in article L.5311-1 of the French Code of Public Health, and does not
      imply any changes in the medical care received by the patients. The study began
      in October 2012 and will end in June 2015. TRIAL REGISTRATION: ID-RCB 2012-A00005
      38.

PMID- 25063461
TI  - Late-onset sepsis in very low birth weight infants: a Brazilian Neonatal Research
      Network Study.
AB  - BACKGROUND: Late-onset sepsis (LOS) is an important cause of morbidity and
      mortality in very low birth weight (VLBW) infants. AIM: To determine the
      incidence, risk factors and etiology of LOS. METHODS: LOS was investigated in a
      multicenter prospective cohort of infants at eight public university neonatal
      intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of
      gestational age, 400-1499 g birth weight, who survived >3 days. RESULTS: Of 1507
      infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with
      LOS were more likely to die. The majority of infections (76%) were caused by Gram
      positive organisms. Independent risk factors for proven LOS were use of central
      venous catheter and mechanical ventilation, age at the first feeding and number
      of days on parenteral nutrition and on mechanical ventilation. CONCLUSION: LOS
      incidence and mortality are high in Brazilian VLBW infants. Most risk factors are
      associated with routine practices at NICU.

PMID- 25063462
TI  - Pediatric appendicitis in a developing country: what are the clinical predictors
      and outcome of perforation?
AB  - OBJECTIVES: This study explored the risk factors and outcomes associated with
      perforation in children who underwent emergency appendicectomies. METHODS: A
      retrospective cross-sectional study was conducted on children <13 years old who
      underwent appendicectomies in a Malaysian hospital in 2007. RESULTS: One hundred
      thirty-four children underwent appendicectomies of which 118 were confirmed
      histologically. Sixty-one (52%) were perforated. Children with perforation had
      significantly longer duration of symptoms (p < 0.001), higher white cell count
      and absolute neutrophil counts (p = 0.013), with longer intra-operative period (p
      < 0.001) and post-operative recovery period (p < 0.001). Of the 52 samples of pus
      collected intra-operatively, 37 (71.1%) yielded positive cultures that were
      predominantly Escherichia coli (n = 27). Both the patients who had Staphylococcus
      aureus cultured from pus collected intra-operatively had significant pyogenic
      complications (scrotal pyocele and intra-abdominal abscess). CONCLUSION: Children
      whose appendicitis were perforated had longer duration of symptoms, higher white
      cell counts and absolute neutrophil counts. Those with S.aureus cultured from
      intra-operative pus appeared to suffer more complications.

PMID- 25063463
TI  - Fate of traumatic pulmonary pseudocyst: factors of resolution.
AB  - BACKGROUND: Traumatic pulmonary pseudocysts are rarely talked about, developing
      in less than 3% of patients with pulmonary parenchymal injuries. Resolution
      usually occurs within a few weeks to a few months. METHOD: A prospective study
      was undertaken in 21 cases treated in Menoufia University Hospital, Egypt from
      August 2011 through August 2013. RESULTS: The overall mean time for complete
      resolution was 61.1 days. The mean time for resolution of simple traumatic
      pulmonary pseudocysts was 21 days (n = 6), and the mean time for resolution of
      complicated (blood filled) traumatic pulmonary pseudocysts was 77.1 days (n =
      15). Mean resolution time was 26.3 days for small pulmonary pseudocysts <=22 mm
      (n = 11) and 99.4 days for those >22 mm (n = 10). The resolution time was 42.6
      days in patients 17-years old or younger (n = 11) and 81.4 days in patients older
      than 17 years (n = 10). CONCLUSION: There was a highly significant difference in
      resolution time between simple and complicated pseudocysts. There was also a
      highly significant delay in the resolution time of pseudocysts larger than 22 mm
      and in patients older than 17 years.

PMID- 25063464
TI  - Pheochromocytoma and tetralogy of Fallot: Coincidence or a rare association?
AB  - We report the case of a 25-year-old woman with tetralogy of Fallot who presented
      with chest pain and hypertension, and on further investigation, was diagnosed
      with a pheochromocytoma in the right adrenal gland. She underwent surgical
      excision of the tumor. While the simultaneous occurrence of these two diseases is
      extremely rare, the suspicion of a possible relationship has been raised in the
      past. 

PMID- 25063465
TI  - Effects of age and gender on right ventricular systolic and diastolic function
      using two-dimensional speckle-tracking strain.
AB  - BACKGROUND: Accurate assessment of the right ventricle is increasingly important.
      Measures of right ventricular (RV) systolic function, including fractional area
      change, tissue Doppler (s' velocity), and tricuspid annular plane systolic
      excursion, show significant variation, and the impacts of age and gender are
      unclear. The aim of this study was to determine the effects of gender and age on
      global and segmental RV systolic and diastolic function using both traditional
      echocardiographic and two-dimensional strain parameters. METHODS: Detailed
      transthoracic echocardiographic studies were performed on 142 healthy adult
      volunteers, with particular emphasis on the right ventricle to determine RV
      dimensions and function, including fractional area change, tricuspid annular
      plane systolic excursion, s' velocity, global and segmental systolic strain, and
      systolic, early diastolic, and late diastolic strain rates. RESULTS: Tricuspid
      annular plane systolic excursion (r = -0.4, P < .001) and RV s' velocity (r = 
      0.5, P < .001) as well as diastolic functional parameters, including
      transtricuspid peak E velocity and RV free wall e' velocity (r = -0.4, P < .001),
      decreased with age. Global systolic strain was also reduced, with differential
      reductions in basal and mid segmental strain with age. Early diastolic strain
      rate decreased, with a corresponding increase in late diastolic strain rate. RV
      function parameters, including fractional area change, e' velocity, strain, and
      strain rate, were significantly lower in men. CONCLUSIONS: RV functional analysis
      by two-dimensional strain demonstrates a small yet significant change in global
      and segmental RV function with age and gender, and therefore adjustment for these
      measures is required in the evaluation of RV function.

PMID- 25063466
TI  - Diagnostic value of three-dimensional contrast-enhanced echocardiography for left
      ventricular volume and ejection fraction measurement in patients with poor
      acoustic windows: a comparison of echocardiography and magnetic resonance
      imaging.
AB  - BACKGROUND: Three-dimensional echocardiography (3DE) is a reliable and
      reproducible tool for assessing left ventricular (LV) function but remains
      sensitive to patient echogenicity. Contrast-enhanced 3DE (C3DE) has the potential
      to improve quantification in challenging patients. The aim of this study was to
      evaluate the impact of temporal resolution, spatial resolution, and image dynamic
      range on LV function assessed using C3DE compared with cardiac magnetic resonance
      imaging (MRI) in patients with poor echogenicity. METHODS: Forty-one patients
      with poor echogenicity who underwent two-dimensional echocardiography (2DE), 3DE,
      C3DE, and MRI were retrospectively investigated. RESULTS: Before contrast
      injection, 24 patients had three or more nonvisible segments. Three cases of 2DE
      and 12 cases of 3DE were not suitable for quantification. LV end-diastolic
      volumes were systematically underestimated by 2DE (142 +/- 58 mL), 3DE (146 +/-
      69 mL), and C3DE (172 +/- 61 mL) compared with MRI (216 +/- 85 mL) (P < .001).
      Similar results were found for LV end-systolic volumes (81 +/- 65 mL for 2DE, 82
      +/- 69 mL for 3DE, and 102 +/- 80 mL for C3DE vs 129 +/- 94 mL for MRI; P <
      .001). C3DE provided the best agreement with MRI (Lin concordance correlation
      coefficients of 0.67, 0.93, and 0.99, respectively, for end-diastolic volume, end
      systolic volume, and ejection fraction) as well as the best measurement
      reproducibility. Finally, ultrasound settings had no significant effect on LV
      volumes and ejection fraction measurements. CONCLUSIONS: In these patients with
      poor ultrasound image quality, C3DE, regardless of instrument settings,
      outperformed 2DE and 3DE to assess LV volumes and ejection fraction and can thus
      be proposed as an acceptable alternative when MRI cannot be performed in this
      subgroup.

PMID- 25063467
TI  - Classic-pattern dyssynchrony and electrical activation delays in pediatric
      dilated cardiomyopathy.
AB  - BACKGROUND: Progressive heart failure leading to transplantation or death is
      common in pediatric dilated cardiomyopathy (DCM), and treatment options are
      limited. Select children with DCM have improved after cardiac resynchronization
      therapy (CRT), but predicting response is challenging. Nonetheless, considering
      the frequency of death or transplantation in this population, identifying any
      candidate would be valuable. Classic-pattern dyssynchrony (CPD) identifies
      mechanical dyssynchrony patterns consistent with underlying electrical activation
      delays and strongly predicts CRT response in adult DCM but has not been evaluated
      in pediatric DCM. The aim of this study was to test the hypothesis that CPD is
      present in a subgroup of patients with pediatric DCM and is associated with
      activation delays. METHODS: Fifty-nine subjects with pediatric DCM (left
      ventricular end-diastolic diameter Z score > 2 and left ventricular ejection
      fraction < 40%) who underwent echocardiography with a functional protocol with
      apical images optimized for two-dimensional speckle-tracking strain analysis
      (EchoPAC) were retrospectively analyzed for CPD. Electrocardiograms were
      evaluated for activation delays (prolonged QRS duration and strict criteria for
      left bundle branch block [LBBB]). Forty control subjects with no cardiac disease
      and good imaging widows were also analyzed. RESULTS: The mean age was 5.4 years
      (range, 1 day to 20 years); idiopathic DCM was most common (57%). Severe
      cardiomyopathy was present in 75% (end-diastolic diameter Z score > 4.6 and left
      ventricular ejection fraction < 32%). CPD was identified in seven subjects (12%),
      and prolonged QRS durations were present in 13 (22%), but only two subjects met
      strict criteria for LBBB. Six of seven subjects in the CPD group had prolonged
      QRS durations, and two of seven had LBBB. No control subjects had CPD. The CPD
      analysis was highly feasible and reproducible. CONCLUSIONS: In this severely
      affected cohort, the small CPD subgroup is potentially important because their
      progressive disease may respond to CRT. CPD is associated with activation delays,
      although not necessarily strict LBBB. This has important potential implications
      for prospective evaluation of CRT in this disease.

PMID- 25063468
TI  - Relationship Between Gambling Severity and Attitudes in Adolescents: Findings
      from a Population-Based Study.
AB  - This study used a nationally representative sample of 14,910 high school
      adolescents, aged 15-19 years. The large sample size presents a unique
      opportunity to evaluate firstly the geographical distribution of gambling
      prevalence, secondly, on a subsample of 5,920 adolescents, we studied the
      association of "no-problem-gambling", "at-risk gambling" and a relatively rare
      condition, "problem gambling", with demographic, environmental and behavioral
      variables. It differs from other studies due to the broad sample, thus enabling
      the combined analysis of the above variables that typically have only been
      studied separately. This integrated analysis, involving multiple variables,
      individual and environmental, allows the control of important covariates.
      Multivariate analysis showed that at-risk/problem gamblers were more likely to be
      engaged in behaviors contrary to social rules/law including heavy episodic
      drinking, tranquillizer/sedatives use as well as to approve gambling and have
      friends who gamble. It's important to emphasize that risk-perception is not
      related to gambling. Furthermore, the great geographical variability of at-risk
      and problem-gambling rates suggest that social aspects have to be considered.
      Currently universal prevention specifically targeting gambling is lacking, thus
      an associative model such as social analysis have been implemented in this study,
      in order to construct the basis for the design of a future prevention program
      based on scientific results and thus having important implications for
      implementation within community based activities. Prevention is fundamental:
      53.5% of underage individuals have engaged in gambling even though legislation
      attempts to restrict access.

PMID- 25063469
TI  - Corset: enabling differential gene expression analysis for de novo assembled
      transcriptomes.
AB  - Next generation sequencing has made it possible to perform differential gene
      expression studies in non-model organisms. For these studies, the need for a
      reference genome is circumvented by performing de novo assembly on the RNA-seq
      data. However, transcriptome assembly produces a multitude of contigs, which must
      be clustered into genes prior to differential gene expression detection. Here we
      present Corset, a method that hierarchically clusters contigs using shared reads
      and expression, then summarizes read counts to clusters, ready for statistical
      testing. Using a range of metrics, we demonstrate that Corset out-performs
      alternative methods. Corset is available from https://code.google.com/p/corset
      project/. 

PMID- 25063470
TI  - The impact of survivin on prognosis and clinicopathology of glioma patients: a
      systematic meta-analysis.
AB  - Up to now, survivin has been recommended as a prognostic and diagnostic indicator
      in glioma patients. However, there are still many controversies. Here, a meta
      analysis was conducted to draw a more definitive conclusion on the correlation of
      survivin with overall survival (OS), age, gender, and WHO grade. Eligible studies
      were available through careful assessment, and then pooled hazard ratios (HRs) or
      odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated. Funnel
      plots were introduced to evaluate the publication bias. Additionally,
      heterogeneity and sensitivity were also evaluated. In the present meta-analysis,
      15 eligible studies with a total of 1,089 patients were incorporated. Survivin
      expression in gliomas correlated with 2-year OS (n = 8; HR 0.17, 95% CI 0.11
      0.26) and 5-year OS (n = 7; HR 0.12, 95% CI 0.07-0.22) in patients. In addition,
      a fixed-effect model revealed a significant association between survivin and age
      (male/+; OR 2.10, 95% CI 1.44-3.05) and survivin and WHO grade (I+II/+; OR 0.27,
      95% CI 0.19-0.38). No heterogeneity was observed across all studies. According to
      Begg's and Egger's test and funnel plot, no publication bias was reported. Taken
      together, our meta-analysis suggests that survivin expression is associated with
      poor survival, older age, and higher WHO grade and could be suggested as a useful
      prognostic and diagnostic biomarker, or an effective therapy target.

PMID- 25063472
TI  - Stereotype threat engenders neural attentional bias toward negative feedback to
      undermine performance.
AB  - Stereotype threat, a situational pressure individuals experience when they fear
      confirming a negative group stereotype, engenders a cascade of physiological
      stress responses, negative appraisals, and performance monitoring processes that
      tax working memory resources necessary for optimal performance. Less is known,
      however, about how stereotype threat biases attentional processing in response to
      performance feedback, and how such attentional biases may undermine performance.
      Women received feedback on math problems in stereotype threatening compared to
      stereotype-neutral contexts while continuous EEG activity was recorded. Findings
      revealed that stereotype threatened women elicited larger midline P100 ERPs,
      increased phase locking between anterior cingulate cortex and dorsolateral
      prefrontal cortex (two regions integral for attentional processes), and increased
      power in left fusiform gyrus in response to negative feedback compared to
      positive feedback and women in stereotype-neutral contexts. Increased power in
      left fusiform gyrus in response to negative feedback predicted underperformance
      on the math task among stereotype threatened women only. Women in stereotype
      neutral contexts exhibited the opposite trend. Findings suggest that in
      stereotype threatening contexts, neural networks integral for attention and
      working memory are biased toward negative, stereotype confirming feedback at very
      early speeds of information processing. This bias, in turn, plays a role in
      undermining performance. 

PMID- 25063471
TI  - Creative motivation: creative achievement predicts cardiac autonomic markers of
      effort during divergent thinking.
AB  - Executive approaches to creativity emphasize that generating creative ideas can
      be hard and requires mental effort. Few studies, however, have examined effort
      related physiological activity during creativity tasks. Using motivational
      intensity theory as a framework, we examined predictors of effort-related cardiac
      activity during a creative challenge. A sample of 111 adults completed a
      divergent thinking task. Sympathetic (PEP and RZ) and parasympathetic (RSA and
      RMSSD) outcomes were assessed using impedance cardiography. As predicted, people
      with high creative achievement (measured with the Creative Achievement
      Questionnaire) showed significantly greater increases in sympathetic activity
      from baseline to task, reflecting higher effort. People with more creative
      achievements generated ideas that were significantly more creative, and creative
      performance correlated marginally with PEP and RZ. The results support the view
      that creative thought can be a mental challenge. 

PMID- 25063473
TI  - Relationships Between Body Image, Body Composition, Sexual Functioning, and
      Sexual Satisfaction Among Heterosexual Young Adults.
AB  - This study investigated the association between body image and body-image self
      consciousness on sexual satisfaction, accounting for relationships between body
      fat and body image, and between sexual functioning and sexual satisfaction, while
      controlling for relationship satisfaction. Participants were 143, 18-25 year-old
      Caucasian men and women in heterosexual monogamous relationships, recruited from
      the University of Guelph and surrounding community in Ontario, Canada. Various
      domains of body image, body-image self-consciousness, sexual satisfaction and
      functioning, and relationship satisfaction data were collected by questionnaires.
      Body fat was measured using dual energy X-ray absorptiometry. Among men, body
      image was positively associated with sexual satisfaction, after controlling for
      relationship satisfaction. Men with greater body fat were more likely to have
      poorer behavioral and affective body image. Only body image specific to the
      sexual encounter influenced sexual functioning. Among women, no domain of body
      image was associated with sexual satisfaction, after controlling for relationship
      satisfaction. Women with greater body fat were more likely to have poorer
      affective and sexual-encounter-specific body image. As percent total fat
      increased, sexual functioning decreased. Our results suggest a complex pattern of
      relationships exists among body image and body composition constructs and sexual
      and relationship variable; and that these relationships are not the same for men
      and women.

PMID- 25063474
TI  - Development of DNA mismatch repair gene, MutS, as a diagnostic marker for
      detection and phylogenetic analysis of algal Megaviruses.
AB  - Megaviruses are generically defined as giant viruses with genomes up to 1.26Mb
      that infect eukaryotic unicellular protists; they are clearly delineated in DNA
      polymerase B phylogenetic trees; in addition, common features often include an
      associated virophage observed during infection; the presence of an amino acyl
      tRNA synthetase gene; and a nucleic acid mismatch repair protein, MutS gene. The
      archetypal representative of this evolving putative family is Mimivirus, an
      opportunistic pathogen of Acanthamoeba spp. originally thought to be a bacterium
      until its genome sequence was published in 2004. Subsequent analysis of marine
      metagenomic data revealed Megaviruses are likely ubiquitous on the surface ocean.
      Analysis of genome sequences of giant viruses isolated from naturally occurring
      marine protists such as microalgae and a microflagellate grazer, started the
      expansion of the Megaviridae. Here, we explored the possibility of developing
      Megavirus specific markers for mutS that could be used in virus molecular ecology
      studies. MutS is split into 15 different clades representing a wide range of
      cellular life, and two that contain Megaviruses, clade MutS7 and clade MutS8. We
      developed specific PCR primers that recognized Megavirus clade MutS8, a clade
      that we propose discriminates most of the algal Megaviruses. Analysis of seawater
      off the coast of Maine, US, revealed novel groups of algal Megaviruses that were
      present in all samples tested. The Megavirus clade MutS8 marker should be
      considered as a tool to reveal new diversity and distribution of this enigmatic
      group of viruses. 

PMID- 25063475
TI  - Calpain activation and CaMKIV reduction in spinal cords from hSOD1G93A mouse
      model.
AB  - Amyotrophic Lateral Sclerosis (ALS), a severe neurodegenerative disease, affects
      the upper and lower motor neurons in the brain and spinal cord. In some studies,
      ALS disease progression has been associated with an increase in calcium-dependent
      degeneration processes. Motoneurons are specifically vulnerable to sustained
      membrane depolarization and excessive elevation of intracellular calcium
      concentration. The present study analyzed intracellular events in embryonic
      motoneurons and adult spinal cords of the hSOD1G93A ALS mouse model. We observed
      activation of calpain, a calcium-dependent cysteine protease that degrades a
      variety of substrates, and a reduction in calcium-calmodulin dependent protein
      kinase type IV (CaMKIV) levels in protein extracts from spinal cords obtained at
      several time-points of hSOD1G93A mice disease progression. However, in cultured
      embryonic motoneurons these differences between controls and hSOD1G93A mutants
      are not evident. Our results support the hypothesis that age-dependent changes in
      calcium homeostasis and resulting events, e.g., calpain activation and CaMKIV
      processing, are involved in ALS pathogenesis.

PMID- 25063476
TI  - Reply to: high-frequency jet ventilation for HIFU.

PMID- 25063477
TI  - Gun-sight, not shotgun, nor gun-shot.

PMID- 25063478
TI  - A stranger in the middle cerebral artery.

PMID- 25063483
TI  - [Endometriosis: increasing concentrations of serum interleukin-1beta and
      interleukin-1sRII is associated with the deep form of this pathology].
AB  - OBJECTIVES: To assess interleukin-1beta (IL-1beta) and its inhibitory soluble
      interleukin-1 receptor type II (IL-1sRII) levels into the serum of patients with
      various forms of endometriosis and normal women, and investigate the correlation
      with disease activity. PATIENTS AND METHODS: In this prospective laboratory study
      (2005-2010), 510 women with histologically proven endometriosis and 93
      endometriosis-free controls have been enrolled. Laparoscopic complete exploration
      of the abdominopelvic cavity and blood samples have been performed in each
      patient. For each serum, IL-1beta and IL-1sRII have been evaluated using Elisa.
      RESULTS: IL-1beta and IL-1sRII have been respectively detectable in 64% and 54.6%
      of serum samples from all 603 women studied. IL-1beta was higher in women with
      deep infiltrating endometriosis (DIE) (mean 10.0pg/mL [0.005-416.2]) than in
      endometriosis-free women (mean 0.5pg/mL [0.01-1.7], P<0.01) or in women with
      superficial endometriosis (SUP) (mean 0.6pg/mL [0.1-2.9], P<0.01). Also, IL-1sRII
      was higher in DIE (mean 236.7pg/mL [0.9-6975]) than in the witness group (mean
      85.0pg/mL [1-235.2], P<0.05) or in SUP (mean 85.1pg/mL [0.6-302], P<0.01).
      CONCLUSION: This study highlights both a marked significant increase in serum IL
      1beta and IL-1sRII levels in DIE compared to SUP and normal women and suggests
      that a defect in the control of IL-1 can impact the pathophysiology of
      endometriosis.

PMID- 25063485
TI  - [Trophoblast: conductor of the maternal immune tolerance].
AB  - Pregnancy is a temporary semi-allograft that survives for nine months. The
      importance of this event for the survival of the species justifies several
      tolerance mechanisms that are put into place at the beginning of pregnancy, some
      of which occur even at the time of implantation. The description of these
      mechanisms underlines the leadership of the trophoblast. The trophoblast is the
      conductor of the events, protects himself by expressing specific antigens and
      regulates the environment of the decidua according to the calendar of the events
      of the pregnancy The trophoblast and the decidual environment attract the
      effectors of immunity, almost all present in the decidua. The immunological
      atmosphere of the decidua evolves during the pregnancy modulating the level of
      activation of the immunological cells and adapting the level of activation to the
      stage of the pregnancy. 

PMID- 25063484
TI  - [Influencing factors on surgical duration of ovarian cystectomy by single-port
      access].
AB  - OBJECTIVES: To evaluate the factors influencing the operative duration of ovarian
      cystectomy by single-port access (SPA). MATERIALS AND METHODS: Observational
      monocentric study from June 2010 to September 2012. Inclusive patients were
      patients with an indication of ovarian cystectomy may be done by laparoscopy. The
      procedures were performed by the SPA system LESS(r). Factors evaluated were BMI
      of the patient, histological nature and size of the cyst. RESULTS: We performed
      54 cystectomy in 49 patients. SPA surgery was successfully completed in 53
      patients. The median operative time was statistically longer for endometriotic
      cysts than dermoid cysts or serous-mucinous cysts (P=0.003). Cases exceeding
      60minutes were significantly higher in the endometriosis group (P=0.005). There
      wasn't correlation found between the BMI of the patient and operative time
      (P=0.5). The operating time wasn't increased according to the size of the cyst
      (P=0.9). CONCLUSION: Endometriotic cysts nature appears to be the only limiting
      factor of cystectomy by SPA. Further studies are needed to evaluate the factors
      that may limit the SPA actions.

PMID- 25063486
TI  - [What psychometric scales can be used to assess psychologic distress of pregnant
      women?].
AB  - Pregnancy can be considered as a maturate crisis, a period of vulnerability,
      ambivalence, anxiety and uncertainty. Antenatal depression has a prevalence that
      can be similar to postpartum depression, which is between 10 to 20% depending on
      the study. Assessing the psychological impact of pregnancy is essential and even
      more, in the case of a complicated pregnancy with maternal or fetal disease. Yet,
      this evaluation remains difficult because of the subjective nature of these
      changes. It is therefore necessary to find and use an appropriate scale to deal
      with antepartum the best way. We have listed the different scales available to
      assess this phenomenon. Seven scales were found and their main characteristics
      were studied. Among them, the scale Edinburgh Prenatal Depression Scale (EPDS)
      seems to be the most used and the Hospital Anxiety and Depression Scale (HADS)
      seems to be the most appropriate. However, it has not been validated in obstetric
      context. 

PMID- 25063487
TI  - A green light for blue light ... without single-dose chemotherapy.

PMID- 25063488
TI  - Microorganisms in subterranean acidic waters within Europe's deepest metal mine.
AB  - The Pyhasalmi mine, central Finland, has operated as a deep metal mine since
      1967. It currently reaches a depth of almost 1500 m, making it the deepest mining
      operation in Europe. Around 900,000 m(3) of metal-rich, extremely acidic water
      are pumped out of the mine each year. The near constant air temperature of ~ 24 
      degrees C together with exposure of sulfidic rock surfaces to air and water, have
      created an environment that is highly suitable for colonization by acidophilic
      mineral-oxidizing microorganisms. Using a combined cultivation-dependent and
      molecular approach, indigenous bacteria in waters at two depths within the mine,
      and of an acid streamer sample were identified and isolated. Iron-oxidizing
      chemolithotrophs (Acidithiobacillus and Leptospirillum spp., and "Ferrovum
      myxofaciens" were the most abundant bacteria in mine water samples, whereas the
      acid streamer community contained a greater proportion of heterotrophic
      acidophiles (Ferrimicrobium acidiphilum and a gammaproteobacterium related to
      Metallibacterium scheffleri). The most abundant isolates obtained from both water
      and streamer samples were all strains of Acidithiobacillus Group IV, a proposed
      separate species of iron-oxidizing acidithiobacilli that has not yet been
      classified as such. Archaea were also detected in water and streamer samples
      using molecular methods, but most were not identified and no isolates were
      obtained.

PMID- 25063489
TI  - Lower blood loss after unicompartmental than total knee arthroplasty.
AB  - PURPOSE: It is intuitive that blood loss is lower after unicompartmental knee
      arthroplasty (UKA), but the difference in potential blood loss between UKA and
      total knee arthroplasty (TKA) has not yet been studied extensively. The
      hypothesis of this study was that blood loss is less important in UKA and that it
      can be performed without transfusion risk, even in preoperative anaemic patients.
      METHODS: A comparative matched retrospective study on 105 (57F/48M) UKA patients
      with a mean (SD) age of 64 (10) years, a mean (SD) BMI of 29.5 (5) kg/m(2) and a
      mean (SD) preoperative haemoglobin (Hb) level of 13.7 (1.5) g/dl was matched with
      105 TKA patients for age, BMI, gender, ASA score and preoperative alignment.
      Blood loss was measured peroperatively and as a substitute for blood loss by mean
      Hb and haematocrit drop at day 2 and 4 postoperatively. RESULTS: Mean (SD)
      visible blood loss was lower for UKA [20 (10) cc vs. 110 (10) cc; P < 0.0001].
      Mean (SD) Hb levels were higher for UKA compared to TKA at day 2 [12.9 (1.4) vs.
      12.1 (1.4) g/dl; P < 0.0001], day 4 [12.7 (1.4) vs. 11.5 (1.6) g/dl; P < 0.0001]
      and day 21 [13.2 (1.4) vs. 12.7 (1.3) g/dl; P = 0.0185]. Hidden blood loss was
      more important for TKA (0.2 vs. 0.6 g/dl). Transfusion rates were 0 % for UKA and
      2 % for TKA. Transfused patients were all female with moderate preoperative
      anaemia (Hb < 11 g/dl) undergoing TKA. CONCLUSIONS: Haemoglobin drop is higher
      with more hidden blood loss in TKA. Patients with preoperative anaemia can
      undergo UKA without a risk for transfusion; however, women with moderate anaemia
      planned for TKA are at risk. The transfusion rate for TKA is, however, very low,
      and so, expected survival of the implant versus risk of co-morbidity should be
      discussed with the patient. LEVEL OF EVIDENCE: Therapeutic study, Level III.

PMID- 25063490
TI  - Anatomical factors influencing patellar tracking in the unstable patellofemoral
      joint.
AB  - PURPOSE: The current study was performed to relate anatomical parameters to in
      vivo patellar tracking for pediatric patients with recurrent patellar
      instability. METHODS: Seven pediatric patients with recurrent patellar
      instability that failed conservative treatment were evaluated using computational
      reconstruction of in vivo patellofemoral function. Computational models were
      created from high-resolution MRI scans of the unloaded knee and lower-resolution
      scans during isometric knee extension at multiple flexion angles. Shape matching
      techniques were applied to replace the low-resolution models of the loaded knee
      with the high-resolution models. Patellar tracking was characterized by the
      bisect offset index (lateral shift) and lateral tilt. Anatomical parameters were
      characterized by the inclination of the lateral ridge of the trochlear groove,
      the tibial tuberosity-trochlear groove distance, the Insall-Salvati index and the
      Caton-Deschamps index. Stepwise multivariable linear regression analysis was used
      to relate patellar tracking to the anatomical parameters. RESULTS: The bisect
      offset index and lateral tilt were significantly correlated with the lateral
      trochlear inclination (p<=0.002) and TT-TG distance (p<0.05), but not the Insall
      Salvati index or the Caton-Deschamps index. For both the bisect offset index and
      lateral tilt, the standardized beta coefficient, used to identify the best
      anatomical predictors of tracking, was larger for the lateral trochlear
      inclination than the TT-TG distance. CONCLUSION: For this population, the
      strongest predictor of lateral maltracking that could lead to patellar
      instability was lateral trochlear inclination. LEVEL OF EVIDENCE: Diagnostic
      study, Level II.

PMID- 25063491
TI  - A novel mathematical model to predict the severity of postoperative functional
      reduction before partial nephrectomy: the importance of calculating resected and
      ischemic volume.
AB  - PURPOSE: Preoperatively predicting postoperative kidney function is an essential
      step to achieve improved renal function and prevent chronic kidney disease. We
      introduce a novel formula especially to calculate resected and ischemic volume
      before partial nephrectomy. We examined whether resected and ischemic volume
      would have value for predicting postoperative renal function. MATERIALS AND
      METHODS: We performed a retrospective cohort study in 210 patients who underwent
      robotic partial nephrectomy between September 2006 and October 2013 at a tertiary
      cancer care center. Based on abdominopelvic computerized tomography and magnetic
      resonance imaging we calculated resected and ischemic volume by the novel
      mathematical formula using integral calculus. We comparatively analyzed resected
      and ischemic volume, and current nephrometry systems to determine the degree of
      association and predictability regarding the severity of the postoperative
      functional reduction. RESULTS: On multivariable analysis resected and ischemic
      volume showed a superior association with the absolute change in estimated
      glomerular filtration rate/percent change in estimated glomerular filtration rate
      (B = 6.5, p = 0.005/B = 6.35, p = 0.009). The ROC AUC revealed accurate
      predictability of resected and ischemic volume on the stratified event of an
      absolute change in estimated glomerular filtration rate/event of percent change
      in estimated glomerular filtration rate compared to 3 representative nephrometry
      systems. The calibration plot of this model was excellent (close to the 45-degree
      line) within the whole range of predicted probabilities. CONCLUSIONS: We report a
      method of preoperatively calculating resected and ischemic volume with a novel
      formula. This method has superior correlation with the absolute and percent
      change in estimated glomerular filtration rate compared to current nephrometry
      systems. The predictive model achieved a strong correlation for the absolute and
      percent change in estimated glomerular filtration rate.

PMID- 25063492
TI  - Prosbiotate: a multicenter, prospective analysis of infectious complications
      after prostate biopsy.
AB  - PURPOSE: Prostate biopsy side effects have a role in the controversy over
      screening for prostate cancer. We measured the precise incidence of infection
      after prostate biopsy and determined risk factors. MATERIALS AND METHODS: We
      performed a prospective, multicenter study in France from April to June 2013. All
      prostate biopsies done during this period were included in study. A web based
      questionnaire was used to identify patient characteristics, biopsy methods and
      postoperative infectious episodes. External audit helped ensure data
      completeness. The primary outcome was the post-biopsy infection rate. We
      determined risk factors for infectious complications using univariate and
      multivariate analysis. RESULTS: The study included 2,718 patients, of whom 6%
      reported receiving antibiotics in the previous 6 months and 7.4% had a history of
      prostatitis. Recommended antibiotic prophylaxis consisting of 2 fluoroquinolone
      tablets 2 hours before examination for prostate biopsy was noted in 78.3% of
      cases. Post-biopsy sepsis was found in 76 subjects (2.8%). On multivariate
      analysis predictors of post-biopsy sepsis were noncompliance with antibiotic
      prophylaxis guidelines (OR 2.3, 95% CI 1.4-3.9, p = 0.001), antibiotic treatment
      in the previous 6 months (OR 2.1, 95% CI 1.1-3.9, p = 0.015) and a history of
      prostatitis (OR 1.7, 95% CI 1.2-2.4, p = 0.002). CONCLUSIONS: In this study the
      incidence of post-prostate biopsy sepsis was 2.8% and no deaths were reported.
      Risk factors identified on multivariate analysis were noncompliance with
      antibiotic prophylaxis according to guidelines, antibiotic treatment in the
      previous 6 months and a history of prostatitis.

PMID- 25063493
TI  - Impact of synchronous metastasis distribution on cancer specific survival in
      renal cell carcinoma after radical nephrectomy with tumor thrombectomy.
AB  - PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of
      the pattern of metastatic disease and response to treatment. We studied the
      impact of metastasis and location on cancer specific survival. MATERIALS AND
      METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus
      who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22
      centers in the United States and Europe were analyzed. Number and location of
      synchronous metastases were compared with respect to patient cancer specific
      survival. Multivariable Cox regression models were used to quantify the impact of
      covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was
      present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had
      an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI
      48.6-53.9) for the entire group. On univariable analysis patients with isolated
      lymph node metastasis had a significantly worse cancer specific survival than
      those with a solitary distant metastasis. The location of distant metastasis did
      not have any significant effect on cancer specific survival. On multivariable
      analysis the presence of lymph node metastasis, isolated distant metastasis and
      multiple distant metastases were independently associated with cancer specific
      survival. Moreover higher tumor thrombus level, papillary histology and the use
      of postoperative systemic therapy were independently associated with worse cancer
      specific survival. CONCLUSIONS: In our multi-institutional series of patients
      with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy,
      almost half of the patients had synchronous lymph node or distant organ
      metastasis. Survival was superior in patients with solitary distant metastasis
      compared to isolated lymph node disease.

PMID- 25063494
TI  - Epithelial-to-mesenchymal transition in penile squamous cell carcinoma.
AB  - PURPOSE: Epithelial-to-mesenchymal transition is a phenomenon in epithelial
      tumors that involves loss of intercellular adhesion, mesenchymal phenotype
      acquisition and enhanced migratory potential. While the epithelial-to-mesenchymal
      transition process has been extensively linked to metastatic progression of
      squamous cell carcinoma, studies of the role of epithelial-to-mesenchymal
      transition in squamous cell carcinoma containing high risk human papillomaviruses
      are scarce. Moreover, to our knowledge epithelial-to-mesenchymal transition
      involvement in human penile squamous cell carcinoma, which can arise through
      transforming HPV infections or independently of HPV, has not been investigated.
      We evaluated the presence of epithelial-to-mesenchymal transition markers and
      their relationship to HPV in penile squamous cell carcinoma. MATERIALS AND
      METHODS: We assessed the expression of E-cadherin, vimentin and the epithelial-to
      mesenchymal transition related transcription factors Twist, Zeb1 and Snail by
      immunohistochemical staining in 64 penile squamous cell carcinoma cases. HPV was
      detected by polymerase chain reaction amplification. RESULTS: Simultaneous loss
      of membranous E-cadherin expression and vimentin over expression were noted in
      43.5% of penile squamous cell carcinoma cases. HPV was significantly associated
      with loss of membranous E-cadherin but not with epithelial-to-mesenchymal
      transition. Recurrence and mortality rates were significantly higher in cases
      showing epithelial-to-mesenchymal transition. CONCLUSIONS: Our findings indicate
      that in penile squamous cell carcinoma epithelial-to-mesenchymal transition is
      associated with poor prognosis but not with the presence of HPV.

PMID- 25063496
TI  - Scalable ex vivo expansion of human mesenchymal stem/stromal cells in
      microcarrier-based stirred culture systems.
AB  - The clinical demand for human mesenchymal stem/stromal cells (MSC) drives the
      need for reproducible, cost-effective, and good manufacturing practices (GMP)
      compliant ex vivo expansion protocols. Bioprocess engineering strategies, namely
      controlled stirred bioreactor systems combined with the use of xenogeneic(xeno)
      free materials, provide proper tools to develop and optimize cell manufacturing
      for the rapid expansion of human MSC for cellular therapies. Herein we describe a
      microcarrier-based stirred culture system operating under xeno-free conditions
      using a controlled stirred-tank bioreactor for an efficient and controlled ex
      vivo expansion of human MSC. This culture platform can be applied to MSC from
      different human sources, as well as different microcarriers and xeno-free medium
      formulations. 

PMID- 25063495
TI  - Painful connections: densification versus fibrosis of fascia.
AB  - Deep fascia has long been considered a source of pain, secondary to nerve pain
      receptors becoming enmeshed within the pathological changes to which fascia are
      subject. Densification and fibrosis are among such changes. They can modify the
      mechanical properties of deep fasciae and damage the function of underlying
      muscles or organs. Distinguishing between these two different changes in fascia,
      and understanding the connective tissue matrix within fascia, together with the
      mechanical forces involved, will make it possible to assign more specific
      treatment modalities to relieve chronic pain syndromes. This review provides an
      overall description of deep fasciae and the mechanical properties in order to
      identify the various alterations that can lead to pain. Diet, exercise, and
      overuse syndromes are able to modify the viscosity of loose connective tissue
      within fascia, causing densification, an alteration that is easily reversible.
      Trauma, surgery, diabetes, and aging alter the fibrous layers of fasciae, leading
      to fascial fibrosis. 

PMID- 25063498
TI  - Generation of Transgenic Rats Using Lentiviral Vectors.
AB  - Transgenesis is a valuable tool with which to study different aspects of gene
      function in the context of the intact organism. During the last two decades a
      tremendous number of transgenic animals have been generated, and the continuous
      improvement of technology and the development of new systems have fostered their
      widespread application in biomedical research. Generally, transgenic animals are
      generated by introducing foreign DNA into fertilized oocytes, which can be
      achieved either by injecting recombinant DNA into the pronucleus or by
      transferring lentiviral particles into the perivitelline space. While mice remain
      the favored species in many laboratories, there are a number of applications
      where the use of rats is advantageous. One such research area is multiple
      sclerosis. Here, several experimental models are available that are closely
      mimicking the human disease, and it is possible to induce neuroinflammation by
      transferring pathogenic T cells which can then be studied by flow cytometry and 2
      photon live imaging. Unlike for mice, the development of transgenic rats has
      encountered some hurdles in the past, e.g., due to a complicated reproductive
      biology and the frailty of the fertilized oocytes in vitro. In this chapter we
      provide a protocol describing how we manipulate single cell embryos in our lab in
      order to efficiently generate transgenic rats in a variety of different strains
      using lentiviral gene transfer. 

PMID- 25063497
TI  - Culture of human limbal epithelial stem cells on tenon's fibroblast feeder
      layers: a translational approach.
AB  - The coculture technique is the standard method to expand ex vivo limbal stem
      cells (LSCs) by using inactivated embryonic murine feeder layers (3T3). Although
      alternative techniques such as amniotic membranes or scaffolds have been
      proposed, feeder layers are still considered to be the best method, due to their
      ability to preserve some critical properties of LSCs such as cell growth and
      viability, stemness phenotype, and clonogenic potential. Furthermore, clinical
      applications of LSCs cultured on 3T3 have taken place. Nevertheless, for an
      improved Good Manufacturing Practice (GMP) compliance, the use of human feeder
      layers as well as a fine standardization of the process is strictly encouraged.
      Here, we describe a translational approach in accordance with GMP regulations to
      culture LSCs onto human Tenon's fibroblasts (TFs). In this chapter, based on our
      experience we identify and analyze issues that often are encountered by
      researchers and discuss solutions to common problems.

PMID- 25063499
TI  - Generation, Expansion, and Differentiation of Human Pluripotent Stem Cell (hPSC)
      Derived Neural Progenitor Cells (NPCs).
AB  - Human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs), a
      multipotent cell population that is capable of near indefinite expansion and
      subsequent differentiation into the various cell types that comprise the central
      nervous system (CNS), could provide an unlimited source of cells for neural
      related cell-based therapies and disease modeling. However, the use of NPCs for
      the study and treatment of a variety of debilitating neurological diseases
      requires the development of scalable and reproducible protocols for their
      generation, expansion, characterization, and neuronal differentiation. Here, we
      describe a serum-free method for the stepwise generation of NPCs from hPSCs
      through the sequential formation of embryoid bodies (EBs) and neuro-epithelial
      like rosettes. NPCs isolated from neural rosette cultures can be homogenously
      expanded while maintaining high expression of pan-neural markers such as SOX1,
      SOX2, and Nestin. Finally, this protocol allows for the robust differentiation of
      NPCs into microtubule-associated protein 2 (MAP2) and beta-Tubulin-III (beta3T)
      positive neurons. 

PMID- 25063500
TI  - Isolation, long-term expansion, and differentiation of murine neural stem cells.
AB  - Stem cells are capable of extensive self-renewal while preserving the ability to
      generate cell progeny that can differentiate into different cell types. Here, we
      describe some methods for the isolation of neural stem cells (NSCs) from the
      adult murine subependymal zone (SEZ), their extensive culturing and the
      assessment of their full developmental potential, particularly with respect to
      their differentiation capacity. The procedure includes chemically defined
      conditions such as absence of serum and addition of specific growth factors, in
      which differentiated cells die and are rapidly eliminated from the culture. In
      contrast, undifferentiated precursors become hypertrophic and proliferate,
      forming clonal spherical clusters called "neurospheres." Experimental
      manipulation of NSCs identifies populations of cells with differential
      restriction in their self-renewal potential and introduces a great interest in
      defining the conditions that guide their differentiation into a variety of
      neuronal and glial subtypes, aspects that have important implications for their
      use in future clinical purposes. 

PMID- 25063501
TI  - Advanced fixation for transmission electron microscopy unveils special
      extracellular matrix within the renal stem/progenitor cell niche.
AB  - As well in light as in transmission electron microscopy can be seen that the
      renal stem/progenitor cell niche shows a special arrangement of two different
      kinds of stem/progenitor cells. Epithelial cells are found in the tip of an
      ureteric bud derived CD ampulla encircled by a special basal lamina. Mesenchymal
      cells are separated from them by a striking interstitial interface. Specimens
      fixed by conventional glutaraldehyde solution show that the interface looks
      bright and unremarkable. In contrast, fixation of specimens with glutaraldehyde
      in combination with cupromeronic blue, ruthenium red, or tannic acid illustrates
      that the interface contains a remarkable network of extracellular matrix spanning
      between epithelial and mesenchymal stem/progenitor cells. After unpacking this
      particular extracellular matrix for electron microscopy, elaboration of related
      functions such as structural composition of contained molecules, binding of
      morphogenetic factors, and influence on parenchyma development is under current
      experimental work. 

PMID- 25063502
TI  - Multiplex immunoassays for quantification of cytokines, growth factors, and other
      proteins in stem cell communication.
AB  - Immunoassays represent valuable and broadly used techniques for detection and
      quantification of proteins. Thanks to their high sensitivity, such techniques are
      powerful for analyzing growth factors, trophic factors, angiogenic factors,
      hormones, cytokines, chemokines, soluble receptors, and other proteins which play
      key roles in intercellular communication and operate as potent regulators of stem
      cell survival, proliferation, differentiation, or cell death. Multiplex
      immunological assays, in contrast to ELISA, offer simultaneous quantification of
      tens of proteins across multiple samples, and have been developed to save time,
      costs, and sample volumes. Among them, planar antibody microarrays and xMAP((r))
      bead-based assays have become particularly popular for characterization of
      proteins secreted by stem cells, as they are relatively easy, highly accurate,
      multiplex to a high degree and a broad spectrum of analytes can be measured.
      Here, we describe protocols for multiplex quantification of secreted proteins
      using Quantibody((r)) microarrays (RayBiotech) and xMAP((r)) assays (Luminex and
      its partners). 

PMID- 25063503
TI  - Application of fluid mechanical force to embryonic sources of hemogenic
      endothelium and hematopoietic stem cells.
AB  - During embryonic development, hemodynamic forces caused by blood flow support
      vascular remodeling, arterialization of luminal endothelium, and hematopoietic
      stem cell (HSC) emergence. Previously, we reported that fluid shear stress plays
      a key role in stimulating nitric oxide (NO) signaling in the aorta-gonad
      mesonephros (AGM) and is essential for definitive hematopoiesis. We employed a
      Dynamic Flow System modified from a cone-and-plate assembly to precisely regulate
      in vitro exposure of AGM cells to a defined pattern of laminar shear stress.
      Here, we present the design of a microfluidic platform accessible to any research
      group that requires small cell numbers and allows for recirculation of paracrine
      signaling factors with minimal damage to nonadherent hematopoietic progenitors
      and stem cells. We detail the assembly of the microfluidic platform using
      commercially available components and provide specific guidance in the use of an
      emerging standard in the measurement of embryonic HSC potential, intravenous
      neonatal transplantation. 

PMID- 25063504
TI  - Electrophysiological recordings from neuroepithelial stem cells.
AB  - During embryonic development, neuroepithelial cells act as neural stem cells by
      renewing themselves. These cells are tightly interconnected and make contact with
      the basement membrane of the neuroepithelium. Under such circumstances,
      intracellular recording with a fine-tipped microelectrode is a successful method
      to study the electrophysiological properties of the neuroepithelial stem cell.
      This chapter describes the detailed techniques of intracellular recording from
      neuroepithelial stem cells. 

PMID- 25063505
TI  - Ca(2+) handling in mouse embryonic stem cell-derived cardiomyocytes.
AB  - Embryonic stem (ES) cells are alternative cell source for cell replacement
      therapy for cardiac diseases, thus it is important to verify if the
      cardiomyocytes derived from ES cells have comparable functional parameters
      similar to the mature cardiomyocytes. Ca(2+) handling is one of the most
      important parameters of cardiomyocyte since it is involved in the regulation of
      several main functions of cardiomyocytes, e.g. the excitation-contraction
      coupling. By applying membrane-permeable fluorescent Ca(2+) indicator and
      confocal microscopy detection system, change of intracellular Ca(2+)
      concentration in ES cell-derived cardiomyocytes can be monitored in real-time
      manner. In this protocol, we describe a method of isolating mouse ES cell-derived
      cardiomyocytes and recording their global and local Ca(2+) transients. 

PMID- 25063506
TI  - Trans-cervical, trans-tracheal approach to proximal tracheo-oesophageal fistula:
      a novel technique.
AB  - Esophageal atresia and tracheo-esophageal fistula (TEF) occur in 1/2400-4500
      births. Whilst the diagnosis of esophageal atresia is readily made shortly after
      birth, patients with an isolated H type TEF can present with varying degrees of
      symptomatology which can pose a diagnostic challenge. A combination of contrast
      esophagogram and endoscopic evaluastion is the most commonly employed
      localization strategy. Despite accurate pre-operative localization, intra
      operative identification of the TEF can prove substantially more challenging. The
      authors of this report describe a novel approach in the management of a proximal
      TEF, which allows direct visualization and cannulation via a trans-cervical,
      trans-tracheal approach. 

PMID- 25063507
TI  - Electrode array misplacement into the superior semicircular canal: as a rare
      complication of cochlear implantation.
AB  - OBJECTIVE: To report electrode array misplacement into the superior semicircular
      canal occurring as an rare complication of cochlear implantation through round
      window insertion, and to explore the causative association between electrode
      array misplacement and cochlear implantation surgical techniques. METHODS: A
      chart review of the electrode array misplacement into the superior semicircular
      canal and their management in 695 patients undergoing cochlear implantation was
      undertaken from January 2003 and January 2014 in Anhui Provincial Hospital.
      RESULTS: There were two children of electrode array misplacement into the
      superior semicircular canal complication, and the rate was 0.28%. CONCLUSIONS:
      Electrode array misplacement into the superior semicircular canal associated with
      cochlear implantation is rare. Surgeons should be aware of that the smaller round
      window maybe the reason of electrode array misplacement through round window
      insertion. Intra-operative neural response telemetry and X-ray can alert the
      surgeon the problem with the array's misplacement, which can be identified by
      postoperative CT.

PMID- 25063508
TI  - Increasing rate of middle ear ventilation tube insertion in children in Denmark.
AB  - OBJECTIVE: To study the incidence rates of middle ear ventilation tube insertion
      in children aged 0 to 15 years in Denmark from 1997 to 2010. METHODS: Using two
      national registers, the Danish National Health Service Register and the Danish
      National Patient Register, practically all cases of middle ear ventilation tube
      insertion performed in Denmark in the period were identified. A possible change
      in incidence rate over time was examined using Poisson regression analysis, while
      the cumulative incidence proportion was estimated using life-tables. RESULTS: A
      total of 502,569 uni- or bilateral ventilation tube insertions distributed among
      269,459 different children were identified. From 1997 to 2010 the age
      standardized incidence rate in 0-15-year-olds increased from 26 to 40 per 1000
      person years with an estimated annual increase of 2.0% (95% confidence interval
      1.9-2.1%). The largest increase in incidence rate was found in 1-year-olds with
      an annual increase of 4.5% (95% confidence interval 4.4-4.6%). Age-specific
      incidence rates remained at maximum around the age of 14 months throughout the
      period. The cumulative incidence proportion for the 2010 birth cohort by the time
      they reach the age of 5 years was estimated to 29% (95% confidence interval 28
      29%). CONCLUSION: The rate for middle ear ventilation tube insertion in Denmark
      was high compared to other developed countries, and an estimated 3 in 10 children
      born in 2010 will undergo at least one ventilation tube insertion before their
      fifth birthday.

PMID- 25063509
TI  - Near real time monitoring of platform sourced pollution using TerraSAR-X over the
      North Sea.
AB  - Continuous operational monitoring by means of remote sensing contributes
      significantly towards less occurrence of oil spills over European waters however,
      operational activities show regular occurrence of accidental and deliberate oil
      spills over the North Sea, particularly from offshore platform installations.
      Since the areas covered by oil spills are usually large and scattered over the
      North Sea, satellite remote sensing particularly Synthetic Aperture Radar (SAR)
      represents an effective tool for operational oil spill detection. This paper
      describes the development of a semi-automated approach for oil spill detection,
      optimized for near real time offshore platform sourced pollution monitoring
      context. Eight feature parameters are extracted from each segmented dark spot.
      The classification algorithm is based on artificial neural network. An initial
      evaluation of this methodology has been carried out on 156 TerraSAR-X images.
      Wind and current history information also have been analyzed for particular cases
      in order to evaluate their influences on spill trajectory. 

PMID- 25063510
TI  - The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in
      man.
AB  - Oxcarbazepine, a second generation antiepileptic drug belonging to the family of
      dibenz[b,f]azepines, is subjected to a rapid and extensive biotransformation.
      Oxcarbazepine demonstrates a low potential for drug interactions because its
      biotransformation is mainly mediated by the reduction pathway instead of
      oxidative pathways, which are very susceptible to drug interactions. The
      reductive metabolism of oxcarbazepine yields a 10-monohydroxy derivative (10,11
      dihydro-10-hydroxy-carbazepine), which is responsible for the pharmacological
      activity. The identity and localization of enzymes participating in the reduction
      of oxcarbazepine in response to this active metabolite have remained unknown
      until now. Thus, we investigated the reductive metabolism of oxcarbazepine in
      human liver subcellular fractions and using recombinant carbonyl reducing
      enzymes. The reduction of oxcarbazepine was shown to occur largely in the liver
      cytosol rather than liver microsomes. Furthermore, the activity and
      stereospecificity of cytosolic carbonyl reducing enzymes toward oxcarbazepine
      were assessed. Of the eight tested enzymes, six reductases were identified to
      contribute to the reduction of oxcarbazepine. The highest activities were
      demonstrated by AKR1C1, AKR1C2, AKR1C3, and AKR1C4. The contribution of CBR1 and
      CBR3 to the reduction of oxcarbazepine was also significant, although their role
      in oxcarbazepine metabolism in vivo is unclear. 

PMID- 25063511
TI  - Cognition in Huntington's disease in manifest, premanifest and converting gene
      carriers over ten years.
AB  - BACKGROUND: Cognitive decline in Huntington's disease (HD) remains an area of
      inconsistencies, especially far from disease onset. OBJECTIVE: To clarify the
      course of cognition in premanifest HD. METHODS: Twenty-six premanifest HD, 19
      manifest HD, and 87 control subjects were followed for ten years, using an
      extensive cognitive battery. Differences in baseline levels and change over time,
      on four factors (motor speed, global cognition, executive functioning (EF), and
      memory) were examined, using multilevel regression analyses. Converters were
      additionally analysed as a separate group. Also, the influence of motor speed and
      predicted years to disease onset on the cognitive factors was studied. RESULTS:
      Manifest HD subjects showed lower baseline scores compared to controls on the
      motor speed (p=0.002), memory (p<0.001) and EF (p<0.001). They additionally
      deteriorated over the ten-year follow-up on memory (p=0.01). Converters
      deteriorated on EF (p=0.04). Further analyses of premanifest subjects 'far from
      and close to predicted onset' revealed lower baseline scores for the 'close'
      group on EF, as compared to controls (p=0.001). They also deteriorated on memory
      (p=0.01). Motor speed substantially mediated the results of the three cognitive
      factors; when added as covariate to the model several baseline and slope
      differences for the cognitive factors ceased to be significant. CONCLUSIONS:
      Memory and EF are highly sensitive for ascertaining deterioration in premanifest
      HD gene carriers, especially in subjects close to onset. Lack of deterioration
      for the subjects further away from onset suggests that both domains are largely
      unaffected in those far from onset. Also, motor influence on cognition is
      substantial and should be taken into account in cognitive HD research.

PMID- 25063512
TI  - Degradation of misfolded proteins by autophagy: is it a strategy for Huntington's
      disease treatment?
AB  - Autophagy is a degradation pathway for long-lived cytoplasmic proteins, protein
      complexes, or damaged organelles. The accumulation and aggregation of misfolded
      proteins are hallmarks of several neurodegenerative diseases. Many researchers
      have reported that autophagy degrades disease-causing misfolded and aggregated
      proteins, including mutant huntingtin (Htt) in Huntington's disease, mutant
      synuclein in familial Parkingson's disease, mutant Cu, Zn-Superoxide dismutase
      (SOD1) in familial amyotrophic lateral sclerosis. In this review, we will bring
      up new evidence to elucidate the involvement of autophagy in degradation of
      mutant Htt, discuss the mechanisms regulating the degradation of mutant Htt by
      autophagy and the therapeutic effects of drugs that enhance autophagy to improve
      clearance of mutant Htt. We propose that enhancement of autophagy by drugs may be
      a strategy to treat or retard progression of Huntington's disease.

PMID- 25063513
TI  - Quality of life in Huntington's disease: a comparative study investigating the
      impact for those with pre-manifest and early manifest disease, and their
      partners.
AB  - BACKGROUND: Given the multifaceted nature of this inherited neurodegenerative
      condition, typically affecting adults in mid-life, it is perhaps not surprising
      that studies indicate poorer Health Related Quality of Life (HrQoL) in those with
      the gene-expansion and, by association, in their families. OBJECTIVE: This study
      aimed to extend the current literature by exploring specific life domains,
      including at an earlier disease stage than usually reported in the HRQoL
      literature, and in a subgroup of gene-negative partners. METHODS: 355
      participants from the TRACK-HD cohort (120 Controls, 118 Pre-HD and 117 early-HD)
      completed standardised self-report measures of HrQoL (SF36 and QoLI), underwent
      clinical assessments of capacity and motor function (UHDRS), semi structured
      interviews assessing neuropsychiatric symptoms (PBA-s), completed paper and
      computerized cognitive tasks and assessment of behaviours associated with damage
      to frontal brain circuits (FrSBe). RESULTS: Each gene-expanded group scored
      statistically significantly lower than gene-negative sibling controls on the SF36
      General Health subscale; neuropsychiatric symptoms and executive dysfunction were
      associated with reduced HrQoL. Those with Stage II disease reported statistically
      significantly lower HrQoL than gene-negative controls across physical, emotional
      and social life domains. Those partnered with manifest participants reported
      lower HrQoL in the social domain compared to those partnered with at-risk
      participants furthest from disease onset; and perseverative symptoms in manifest
      partners were found to be related to lower HrQoL in their gene-negative partners.
      HrQoL in gene-negative partners of pre-manifest individuals was associated with
      pre-manifest individuals' neuropsychiatric and cognitive function. CONCLUSIONS:
      Understanding the nature and timing of disruption to the HrQoL in people who are
      pre-manifest and diagnosed with HD, and their gene-negative partners, can inform
      the development of appropriate strategies and interventions.

PMID- 25063514
TI  - Postural limits of stability in premanifest and manifest Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is associated with neuronal death in basal
      ganglia circuits important for postural control. Despite evidence of postural
      instability associated with HD, postural control at the limits of stability has
      not been investigated in this disease. OBJECTIVE: To use computerized dynamic
      posturography to measure postural control at the limits of stability during the
      premanifest and manifest stages of HD. METHODS: Patients with manifest HD,
      premanifest gene carriers, and matched controls stood on mechanically locked
      force plates while viewing a computer screen. The participant's estimated center
      of gravity was represented on the screen as a cursor along with eight target
      icons arranged in a circular pattern at the theoretical edge of limits of
      stability. On each trial, one of the eight targets was highlighted and the
      participant was instructed to control the cursor by rapidly shifting his/her
      weight in the direction of the target. Measures included reaction time, movement
      velocity, endpoint excursion, maximum excursion, and directional control.
      RESULTS: Analysis of variance revealed significant impairment on endpoint
      excursion, maximum excursion, and directional control (p<=0.001) in the
      Huntington's disease group, but not in the premanifest gene carrier group as
      compared to controls. No differences were found on reaction time or movement
      velocity measures. Group signal to noise ratios also were examined for the
      measures. CONCLUSIONS: HD patients, but not premanifest gene carriers, showed
      impaired postural control at the limits of stability. Impaired performance in HD
      patients has potential functional consequences including increased risk of
      falling during weight-shifting activities.

PMID- 25063515
TI  - Reference genes selection for transcriptional profiling in blood of HD patients
      and R6/2 mice.
AB  - BACKGROUND: Huntington's disease is a neurodegenerative disorder characterized by
      transcriptional alterations both in central and peripheral tissues. Therefore,
      the identification of a transcriptional signature in an accessible tissue can
      meaningfully complement current efforts in clinical biomarker development. Gene
      expression normalization represents an essential step in transcriptional
      signatures identification, and since many reference genes show altered
      expressions in several pathologies, the definition of stable genes in the desired
      tissue is required to allow correct result interpretations. OBJECTIVE: The
      present work aimed at identifying a set of suitable reference genes for
      expression normalization in blood of HD patients and R6/2 mice. METHODS: By
      crossing literature investigation and analysis of microarrays performed on blood
      of HD patients and healthy subjects, a set of genes was selected and tested by RT
      qPCR. Employment of statistical algorithms allowed the identification of the most
      stable genes in human samples that were than confirmed in R6/2. RESULTS: PPIB,
      PGK1, ACTB and YWHAZ represent the best possible genes combination, useful to
      normalize blood transcriptional analysis. To link clinical and preclinical
      studies, the identified genes were investigated also in blood of R6/2 and wild
      type mice, confirming that Ppib, Actb and Ywhaz were appropriate for expression
      normalization. Selected references were subsequently applied to evaluate
      expression of genes known to be involved in Huntington's pathological
      progression. CONCLUSIONS: This work highlights the importance for correct data
      normalization to avoid misinterpretation of results, while providing a suitable
      method to support quantitative gene expression analysis in preclinical and
      clinical investigations.

PMID- 25063516
TI  - Antisense oligonucleotide-mediated correction of transcriptional dysregulation is
      correlated with behavioral benefits in the YAC128 mouse model of Huntington's
      disease.
AB  - BACKGROUND: Huntington's disease (HD) is a neurological disorder caused by
      mutations in the huntingtin (HTT) gene, the product of which leads to selective
      and progressive neuronal cell death in the striatum and cortex. Transcriptional
      dysregulation has emerged as a core pathologic feature in the CNS of human and
      animal models of HD. It is still unclear whether perturbations in gene expression
      are a consequence of the disease or importantly, contribute to the pathogenesis
      of HD. OBJECTIVE: To examine if transcriptional dysregulation can be ameliorated
      with antisense oligonucleotides that reduce levels of mutant Htt and provide
      therapeutic benefit in the YAC128 mouse model of HD. METHODS: Quantitative real
      time PCR analysis was used to evaluate dysregulation of a subset of striatal
      genes in the YAC128 mouse model. Transcripts were then evaluated following ICV
      delivery of antisense oligonucleotides (ASO). Rota rod and Porsolt swim tests
      were used to evaluate phenotypic deficits in these mice following ASO treatment.
      RESULTS: Transcriptional dysregulation was detected in the YAC128 mouse model and
      appears to progress with age. ICV delivery of ASOs directed against mutant Htt
      resulted in reduction in mutant Htt levels and amelioration in behavioral
      deficits in the YAC128 mouse model. These improvements were correlated with
      improvements in the levels of several dysregulated striatal transcripts.
      CONCLUSIONS: The role of transcriptional dysregulation in the pathogenesis of
      Huntington's disease is not well understood, however, a wealth of evidence now
      strongly suggests that changes in transcriptional signatures are a prominent
      feature in the brains of both HD patients and animal models of the disease. Our
      study is the first to show that a therapeutic agent capable of improving an HD
      disease phenotype is concomitantly correlated with normalization of a subset of
      dysregulated striatal transcripts. Our data suggests that correction of these
      disease-altered transcripts may underlie, at least in part, the therapeutic
      efficacy shown associated with ASO-mediated correction of HD phenotypes and may
      provide a novel set of early biomarkers for evaluating future therapeutic
      concepts for HD.

PMID- 25063517
TI  - Influence of thylakoid membrane lipids on the structure and function of the plant
      photosystem II core complex.
AB  - MAIN CONCLUSION: MGDG leads to a dimerization of isolated, monomeric PSII core
      complexes. SQDG and PG induce a detachment of CP43 from the PSII core, thereby
      disturbing the intrinsic PSII electron transport. The influence of the four
      thylakoid membrane lipids monogalactosyldiacylglycerol (MGDG),
      digalactosyldiacylglycerol (DGDG), sulfoquinovosyldiacylglycerol (SQDG) and
      phosphatidylglycerol (PG) on the structure and function of isolated monomeric
      photosystem (PS) II core complexes was investigated. Incubation with the
      negatively charged lipids SQDG and PG led to a loss of the long-wavelength 77 K
      fluorescence emission at 693 nm that is associated with the inner antenna
      proteins. The neutral galactolipids DGDG and MGDG had no or only minor effects on
      the fluorescence emission spectra of the PSII core complexes, respectively.
      Pigment analysis, absorption and 77 K fluorescence excitation spectroscopy showed
      that incubation with SQDG and PG led to an exposure of chlorophyll molecules to
      the surrounding medium followed by conversion to pheophytin under acidic
      conditions. Size-exclusion chromatography and polypeptide analysis corroborated
      the findings of the spectroscopic measurements and pigment analysis. They showed
      that the negatively charged lipid SQDG led to a dissociation of the inner antenna
      protein CP43 and the 27- and 25-kDa apoproteins of the light-harvesting complex
      II, that were also associated with a part of the PSII core complexes used in the
      present study. Incubation of PSII core complexes with MGDG, on the other hand,
      induced an almost complete dimerization of the monomeric PSII. Measurements of
      the fast PSII fluorescence induction demonstrated that MGDG and DGDG only had a
      minor influence on the reduction kinetics of plastoquinone QA and the artificial
      PSII electron acceptor 2,5-dimethyl-p-benzoquinone (DMBQ). SQDG and, to a lesser
      extent, PG perturbed the intrinsic PSII electron transport significantly.

PMID- 25063518
TI  - The impact of economic crises on social inequalities in health: what do we know
      so far?
AB  - Since 2008, Western countries are going through a deep economic crisis whose
      health impacts seem to be fundamentally counter-cyclical: when economic
      conditions worsen, so does health, and mortality tends to rise. While a growing
      number of studies have presented evidence on the effect of crises on the average
      population health, a largely neglected aspect of research is the impact of crises
      and the related political responses on social inequalities in health, even if the
      negative consequences of the crises are primarily borne by the most disadvantaged
      populations. This commentary will reflect on the results of the studies that have
      analyzed the effect of economic crises on social inequalities in health up to
      2013. With some exceptions, the studies show an increase in health inequalities
      during crises, especially during the Southeast Asian and Japanese crises and the
      Soviet Union crisis, although it is not always evident for both sexes or all
      health or socioeconomic variables. In the Nordic countries during the nineties, a
      clear worsening of health equity did not occur. Results about the impacts of the
      current economic recession on health equity are still inconsistent. Some of the
      factors that could explain this variability in results are the role of welfare
      state policies, the diversity of time periods used in the analyses, the
      heterogeneity of socioeconomic and health variables considered, the changes in
      the socioeconomic profile of the groups under comparison in times of crises, and
      the type of measures used to analyze the magnitude of social inequalities in
      health. Social epidemiology should further collaborate with other disciplines to
      help produce more accurate and useful evidence about the relationship between
      crises and health equity. 

PMID- 25063520
TI  - Tumor-based case-control studies of infection and cancer: muddling the when and
      where of molecular epidemiology.
AB  - We describe the "tumor-based case-control" study as a type of epidemiologic study
      used to evaluate associations between infectious agents and cancer. These studies
      assess exposure using diseased tissues from affected individuals (i.e.,
      evaluating tumor tissue for cancer cases), but they must utilize nondiseased
      tissues to assess control subjects, who do not have the disease of interest. This
      approach can lead to exposure misclassification in two ways. First, concerning
      the "when" of exposure assessment, retrospective assessment of tissues may not
      accurately measure exposure at the key earlier time point (i.e., during the
      etiologic window). Second, concerning the "where" of exposure assessment, use of
      different tissues in cases and controls can have different accuracy for detecting
      the exposure (i.e., differential exposure misclassification). We present an
      example concerning the association of human papillomavirus with various cancers,
      where tumor-based case-control studies likely overestimate risk associated with
      infection. In another example, we illustrate how tumor-based case-control studies
      of Helicobacter pylori and gastric cancer underestimate risk. Tumor-based case
      control studies can demonstrate infection within tumor cells, providing
      qualitative information about disease etiology. However, measures of association
      calculated in tumor-based case-control studies are prone to over- or
      underestimating the relationship between infections and subsequent cancer risk.

PMID- 25063519
TI  - Are HIV-infected men vulnerable to prostate cancer treatment disparities?
AB  - BACKGROUND: HIV-infected (HIV(+)) men face cancer treatment disparities that
      impact outcome. Prostate cancer treatment and treatment appropriateness in HIV(+)
      men are unknown. METHODS: We used electronic chart review to conduct a
      retrospective cohort study of 43 HIV(+) cases with prostate cancer and 86 age-
      and race-matched HIV-uninfected (HIV(-)) controls with prostate cancer, ages 40
      to 79 years, from 2001 to 2012. We defined treatment appropriateness using
      National Comprehensive Cancer Network guidelines and the Charlson comorbidity
      index (CCI) to estimate life expectancy. RESULTS: Median age was 59.5 years at
      prostate cancer diagnosis. Median CD4(+) T-cell count was 459.5 cells/mm(3),
      95.3% received antiretroviral therapy, and 87.1% were virally suppressed. Radical
      prostatectomy was the primary treatment for 39.5% of HIV(+) and 71.0% of HIV(-)
      men (P = 0.004). Only 16.3% of HIV(+) versus 57.0% of HIV(-) men received open
      radical prostatectomy (P < 0.001). HIV(+) men received more radiotherapy (25.6%
      vs. 16.3%, P = 0.13). HIV was negatively associated with open radical
      prostatectomy (OR = 0.03, P = 0.007), adjusting for insurance and CCI. No men
      were undertreated. Fewer HIV(+) men received appropriate treatment (89.2% vs.
      100%, P = 0.003), due to four overtreated HIV(+) men. Excluding AIDS from the CCI
      still resulted in fewer HIV(+) men receiving appropriate treatment (94.6% vs.
      100%, P = 0.03). CONCLUSION: Prostate cancer in HIV(+) men is largely
      appropriately treated. Under- or overtreatment may occur from difficulties in
      life expectancy estimation. HIV(+) men may receive more radiotherapy and fewer
      radical prostatectomies, specifically open radical prostatectomies. IMPACT:
      Research on HIV/AIDS survival indices and etiologies and outcomes of this
      prostate cancer treatment disparity in HIV(+) men are needed.

PMID- 25063521
TI  - A risk prediction model for smoking experimentation in Mexican American youth.
AB  - BACKGROUND: Smoking experimentation in Mexican American youth is problematic. In
      light of the research showing that preventing smoking experimentation is a valid
      strategy for smoking prevention, there is a need to identify Mexican American
      youth at high risk for experimentation. METHODS: A prospective population-based
      cohort of 1,179 adolescents of Mexican descent was followed for 5 years starting
      in 2005-06. Participants completed a baseline interview at a home visit followed
      by three telephone interviews at intervals of approximately 6 months and
      additional interviews at two home visits in 2008-09 and 2010-11. The primary
      endpoint of interest in this study was smoking experimentation. Information about
      social, cultural, and behavioral factors (e.g., acculturation, susceptibility to
      experimentation, home characteristics, and household influences) was collected at
      baseline using validated questionnaires. RESULTS: Age, sex, cognitive
      susceptibility, household smoking behavior, peer influence, neighborhood
      influence, acculturation, work characteristics, positive outcome expectations,
      family cohesion, degree of tension, ability to concentrate, and school discipline
      were found to be associated with smoking experimentation. In a validation
      dataset, the proposed risk prediction model had an area under the receiver
      operating characteristic curve (AUC) of 0.719 (95% confidence interval, 0.637
      0.801) for predicting absolute risk for smoking experimentation within 1 year.
      CONCLUSIONS: The proposed risk prediction model is able to quantify the risk of
      smoking experimentation in Mexican American adolescents. IMPACT: Accurately
      identifying Mexican American adolescents who are at higher risk for smoking
      experimentation who can be intervened will substantially reduce the incidence of
      smoking and thereby subsequent health risks.

PMID- 25063522
TI  - Low folate levels are associated with reduced risk of colorectal cancer in a
      population with low folate status.
AB  - BACKGROUND: A diet rich in folate is associated with a reduced colorectal cancer
      risk, whereas the role of circulating levels is less clear. The aim of this study
      was to relate prediagnostic plasma folate, vitamin B12, and homocysteine
      concentrations to the risk of colorectal cancer. METHODS: This was a prospective
      case-control study of 331 cases and 662 matched controls nested within the
      population-based Northern Sweden Health and Disease Study. Median follow-up time
      from recruitment to diagnosis was 10.8 years. RESULTS: Plasma folate
      concentrations were positively related to colorectal cancer risk; multivariate
      odds ratios were 1.62 [95% confidence intervals (CI), 1.08-2.42] and 1.42 (95%
      CI, 0.94-2.21) for the middle and highest versus lowest tertile, respectively. In
      subjects with follow-up <10.8 years, a statistically significant doubled risk was
      observed for the middle and highest versus lowest tertile, whereas findings for
      longer follow-up times were null. A positive risk relationship was also observed
      for tumor stage III-IV but not I-II. Plasma vitamin B12 concentrations were
      inversely associated with rectal cancer risk. Homocysteine was not significantly
      related to colorectal cancer risk. CONCLUSIONS: In this population-based, nested
      case-control study, low plasma folate concentrations were associated with a
      reduced colorectal cancer risk. This protective role was mainly observed in
      subjects with higher tumor stage or shorter follow-up time between recruitment
      and diagnosis. Low circulating folate status may protect against colorectal
      cancer or suppress progression of preneoplastic or neoplastic lesions. IMPACT:
      These findings may have relevance for the ongoing debate about mandatory folic
      acid fortification of flour.

PMID- 25063523
TI  - Toward adjunctive therapy of acute myeloid leukemia: is it feasible?

PMID- 25063524
TI  - Appropriate use of bendamustine in first-line therapy of chronic lymphocytic
      leukemia. Recommendations from SIE, SIES, GITMO Group.
AB  - By using the GRADE system we produced the following recommendations for the use
      of bendamustine in the first-line treatment of CLL: (1) bendamustine with
      rituximab is recommended in elderly fit patients potentially eligible to FCR; (2)
      Bendamustine alone is recommended in patients who are candidate to chlorambucil
      alone; (3) Rituximab-bendamustine is recommended in patients not eligible to FCR,
      but suitable to receive rituximab. Consensus-based recommendations addressed
      evidence-orphan issues concerning the use of bendamustine in genetically-defined
      high-risk patients and the appropriate dose of bendamustine as single agent or in
      association with rituximab. 

PMID- 25063525
TI  - Genetic and cytokine changes associated with symptomatic stages of CLL.
AB  - The pathogenesis and drug resistance of symptomatic CLL patients involves genetic
      changes associated with the CLL clone as well as changes within the
      microenvironment. To further understand these processes, we compared early stage
      CLL to symptomatic late stage using gene expression and serum cytokine profiling
      to gain insight of the genetic and microenvironment changes associated with the
      most severe form of the disease. Patients were classified into low stage (Rai
      stage 0/I/II) and high stage (Rai stage III/IV). Gene expression profiles were
      obtained on pretreatment samples using the HG-U133A 2.0 Affymetrix platform. A
      comparison of low versus high stage CLL revealed a set of 21 genes differentially
      expressed genes. 15 genes were up regulated in the high stage compared to low
      stage while 6 genes were down regulated. Analysis of GO molecular function
      revealed 9 of 21 genes were involved in transcription factor activity. Serum
      cytokine profiles showed six cytokines to be significantly different in high
      stage patients. Two chemokines, SDF-1/CXCL12 and uPAR known to be involved in
      stem cell mobilization and homing were increased in serum of high stage patients.
      This study has identified therapeutic targets for symptomatic CLL patients. 

PMID- 25063526
TI  - Arhgef16, a novel Elmo1 binding partner, promotes clearance of apoptotic cells
      via RhoG-dependent Rac1 activation.
AB  - Elmo is an evolutionarily conserved mammalian ortholog of Caenorhabditis elegans
      CED-12 with proposed roles during the removal of apoptotic cells, cell migration,
      neurite outgrowth, and myoblast fusion (Katoh and Negishi (2003) [1], Park and
      Tosello (2007) [2], Grimsley et al. (2004) [3], Hamoud et al. (2014) [4]). Elmo
      mediates these cellular processes by interacting with various proteins located in
      the plasma membrane, cytoplasm and nucleus, and by modulating their activities
      although it has no intrinsic catalytic activity (Park and Tosello (2007) [2],
      Hamoud et al. (2014) [4], Li et al. (2013) [5], Margaron, Fradet and Cote (2013)
      [6], and Mauldin et al. (2013)[7]). Because there are a limited number of
      proteins known to interact with Elmo, we performed a yeast two-hybrid screen
      using Elmo1 as bait to identify Elmo1-interacting proteins and to evaluate their
      mode of regulation. Arhgef16 was one of the proteins identified through the
      screen and subsequent analyses revealed that Arhgef16 interacted with Elmo1 in
      mammalian cells as well. Expression of Arhgef16 in phagocytes promoted engulfment
      of apoptotic cells, and engulfment mediated by Arhgef16 increased synergistically
      in the presence of Elmo1 but was abrogated in the absence of Elmo1. In addition,
      Arhgef16-mediated removal of apoptotic cells was dependent on RhoG, but
      independent of Dock1. Taken together, this study suggests that the newly
      identified Elmo1-interacting protein, Arhgef16, functions synergistically with
      Elmo1 to promote clearance of apoptotic cells in a RhoG-dependent and Dock1
      independent manner. 

PMID- 25063527
TI  - Are results of total knee arthroplasty for isolated patellofemoral OA as good as
      for medial compartment OA? A medium-term retrospective comparative study.
AB  - PURPOSE: The aim of this study was to compare the results of isolated
      patellofemoral arthritis (IPFA) treated using a total knee arthroplasty (TKA)
      compared to the results of medial tibiofemoral arthritis treated with a TKA. We
      hypothesised that there would be no difference between functional outcomes for
      the two groups. METHODS: Between 2003 and 2009, 32 TKAs were performed for IPFA
      (group I). Over this time period, a total of 813 primary TKAs were performed from
      which we identified a second group of patients who had undergone TKA for isolated
      medial tibiofemoral arthritis (group II: n = 32). These patients were matched
      based on age, sex, body mass index and average follow-up. The average age of
      patients in group I was 72.81 +/- 6.6 years (59-83) and 71.97 +/- 6.8 years in
      group II. The global International Knee Society (IKS) score was statistically
      significantly better in group I (114.72 +/- 22 points) than in group II (84.9 +/-
      23.8). This difference was accounted for by better passive flexion, better
      walking distance and the absence of any coronal plane deformity. RESULTS: A total
      of 29 patients from group I were reviewed at an average follow-up of 64.58 +/-
      23.4 months, and 30 patients in group II were reviewed at an average follow-up of
      66.13 +/- 23.9 months (three were lost to follow-up in group I and two in group
      II). At final follow-up, there was statistically no difference between the two
      groups IKS score (175.34 +/- 19.26 in group I vs. 170.13 +/- 24.14 for group II)
      or Hospital for Special Surgery patella score (89.31 +/- 9.98 points for group I
      vs. 89.16 +/- 11.45 points for group II). We found no significant radiological
      difference between the two groups including patella height and orientation on
      axial views. CONCLUSIONS: The results of TKA for IPFA are as good as the results
      of TKA for isolated medial tibiofemoral arthritis with well-functioning
      prosthetic patellofemoral articulations. These results support our institutional
      preference for using TKA as treatment for IPFA in patients over 65-70 years old.

PMID- 25063528
TI  - Computational discovery of feature patterns in nucleosomal DNA sequences.
AB  - The identification of important factors that affect nucleosome formation is
      critical to clarify nucleosome-forming mechanisms and the role of the nucleosome
      in gene regulation. Various features reported in the literature led to our
      hypothesis that multiple features can together contribute to nucleosome
      formation. Therefore, we compiled 779 features and developed a pattern discovery
      and scoring algorithm FFN (Finding Features for Nucleosomes) to identify feature
      patterns that are differentially enriched in nucleosome-forming sequences and
      nucleosome-depletion sequences. Applying FFN to genome-wide nucleosome occupancy
      data in yeast and human, we identified statistically significant feature patterns
      that may influence nucleosome formation, many of which are common to the two
      species. We found that both sequence and structural features are important in
      nucleosome occupancy prediction. We discovered that, even for the same feature
      combinations, variations in feature values may lead to differences in predictive
      power. We demonstrated that the identified feature patterns could be used to
      assist nucleosomal sequence prediction. 

PMID- 25063529
TI  - Integrating epigenetic marks for identification of transcriptionally active
      miRNAs.
AB  - MicroRNAs have been identified as important regulators involved in biological
      processes and human diseases. We proposed a computational approach to systematic
      identification of active promoters of miRNAs by active models using epigenetic
      characteristics at active promoters of protein-coding genes together with a
      genomic context-based filtering step in nine human cell types, which were
      validated to exhibit greater conservation, more overlap with CAGE-identified
      TSSs, more conserved TFBSs and higher transcription factor binding signal
      intensities. Furthermore, expression analysis showed discordance between
      transcriptional activation of miRNAs and expression of their precursor and mature
      forms, indicating that precursor and mature miRNA expression is insufficient to
      account for transcriptional activation of miRNAs. Compared to other methods, our
      approach identified higher percentages of active miRNAs with CAGE-detected TSS
      activity and primary transcript expression, further supporting the validity of
      our approach, which will be valuable to understand the biological roles of miRNAs
      in specific cell contexts. 

PMID- 25063531
TI  - A minimally invasive off-pump implantation technique for continuous-flow left
      ventricular assist devices: early experience.
AB  - BACKGROUND: The HeartWare (HeartWare International, Inc. Framingham, MA)
      ventricular assist device (HVAD) is approved for implantation through a
      sternotomy with cardiopulmonary bypass. We report on our initial experience with
      this device implanted off-pump via thoracotomy. METHODS: A total of 26 patients
      were included in this review. All patients were Interagency Registry for
      Mechanically Assisted Circulatory Support categories 2 or 3 and underwent
      implantation of an HVAD as an elective procedure via thoracotomy and mini
      sternotomy approach. Three-dimensional echocardiography was used to assess the
      ventricle and was also used to facilitate proper pump positioning. Patients were
      managed during follow-up using anti-coagulants at a target international
      normalized ratio 2.0 to 2.5 as well as anti-platelet agents. RESULTS:
      Implantation was performed without the use of cardiopulmonary bypass, but 1
      patient did require conversion to on-pump surgery. There were no perioperative
      deaths or right heart failure events. The mean intensive care unit stay was 1.5
      days. Transfusions of 1 to 3 units of packed red blood cells were required in 16
      patients, whereas 10 patients maintained a stable perioperative hematocrit of at
      least 30% and did not require transfusion. Survival through 90 days was 100%, and
      survival through 180 days was 87%. CONCLUSIONS: Our experience was favorable in
      respect to outcome, safety, and use of blood products. Our technique can be used
      as an alternative approach for left ventricular assist device implantation using
      the HVAD.

PMID- 25063530
TI  - Tumor necrosis factor-alpha- and interleukin-1beta-dependent matrix
      metalloproteinase-3 expression in nucleus pulposus cells requires cooperative
      signaling via syndecan 4 and mitogen-activated protein kinase-NF-kappaB axis:
      implications in inflammatory disc disease.
AB  - Matrix metalloproteinase-3 (MMP-3) plays an important role in intervertebral disc
      degeneration, a ubiquitous condition closely linked to low back pain and
      disability. Elevated expression of syndecan 4, a cell surface heparan sulfate
      proteoglycan, actively controls disc matrix catabolism. However, the relationship
      between MMP-3 expression and syndecan 4 in the context of inflammatory disc
      disease has not been clearly defined. We investigated the mechanisms by which
      cytokines control MMP-3 expression in rat and human nucleus pulposus cells.
      Cytokine treatment increased MMP-3 expression and promoter activity. Stable
      silencing of syndecan 4 blocked cytokine-mediated MMP-3 expression; more
      important, syndecan 4 did not mediate its effects through NF-kappaB or mitogen
      activated protein kinase (MAPK) pathways. However, treatment with MAPK and NF
      kappaB inhibitors resulted in partial blocking of the inductive effect of
      cytokines on MMP-3 expression. Loss-of-function studies confirmed that NF-kappaB,
      p38alpha/beta2/gamma/delta, and extracellular signal-regulated kinase (ERK) 2,
      but not ERK1, contributed to cytokine-dependent induction of MMP3 promoter
      activity. Similarly, inhibitor treatments, lentiviral short hairpin-p65, and
      short hairpin-IkappaB kinase beta significantly decreased cytokine-dependent up
      regulation in MMP-3 expression. Finally, we show that transforming growth factor
      beta can block the up-regulation of MMP-3 induced by tumor necrosis factor (TNF)
      alpha by counteracting the NF-kappaB pathway and syndecan 4 expression. Taken
      together, our results suggest that cooperative signaling through syndecan 4 and
      the TNF receptor 1-MAPK-NF-kappaB axis is required for TNF-alpha-dependent
      expression of MMP-3 in nucleus pulposus cells. Controlling these pathways may
      slow the progression of intervertebral disc degeneration and matrix catabolism. 

PMID- 25063532
TI  - Mechanical removal of dendritic cell-generating non-classical monocytes via ex
      vivo lung perfusion.
AB  - BACKGROUND: Ex vivo lung perfusion (EVLP) is a novel procedure designed to
      rapidly assess and recondition unusable donor lungs for transplantation (LTx).
      EVLP may reduce graft immunogenicity and allorecognition via removal of passenger
      leukocytes. We aimed to explore this hypothesis using human EVLP and in vitro
      analysis. METHODS: Explanted human lungs (n = 7) underwent standard EVLP.
      Perfusate samples and the leukocyte filter were collected, and cells
      characterized via flow cytometry. Isolated alveolar monocytes (from post-LTx
      bronchoalveolar lavage) were differentiated to dendritic cells and characterized
      (n = 10). An in vitro (air epithelial-liquid endothelial) lung model was utilized
      to evaluate monocyte migration and differentiation within the lung. RESULTS: Non
      classical monocytes (NCM, normally <1% of total white blood cell repertoire)
      mobilized within 30 minutes of EVLP and represented 80.04% of the passenger
      leukocyte population. This subset readily differentiated to dendritic cells and
      secreted pro-inflammatory cytokines (interferon-gamma and interleukin-2) after
      stimulation. NCM rapidly diapedesed from the vascular bed to the alveolus and,
      when cultured on the alveolus, differentiated to dendritic cells with
      inflammatory phenotypes. CONCLUSIONS: The lung possesses a reservoir of NCM,
      which can readily diapedese to the alveolus or mobilize in the circulation. After
      activation, NCM differentiate to inflammatory dendritic cells with T-cell co
      stimulatory capacity. EVLP may impart additional benefits after LTx via the
      removal of passenger monocytes, which may represent a previously unidentified
      beneficial mechanism of action.

PMID- 25063533
TI  - Laparoscopic gastric bypass during left ventricular assist device support and
      ventricular recovery.

PMID- 25063534
TI  - Determination of trace heavy metals in harvested rainwater used for drinking in
      Hebron (south West Bank, Palestine) by ICP-MS.
AB  - Rainwater samples harvested for drinking from the west part of Hebron (south of
      West Bank in Palestine), the largest city in the West Bank, were analyzed for the
      content of different trace heavy metals (Cr, Mn, Co, Ni, Cu, Zn, Mo, Ag, Cd, Bi,
      and Pb) by inductively coupled plasma mass spectrometry (ICP-MS). This study was
      conducted to determine the water quality of harvested rainwater used for drinking
      of south West Bank (case study, Hebron area). A total of 44 water samples were
      collected in November 2012 from 44 house cisterns used to collect rainwater from
      the roofs of houses. The samples were analyzed for their pH, temperature,
      electrical conductivity, total dissolved solids, and different heavy metal
      contents. The pH of all water samples was within the US Environmental Protection
      Agency limits (6.5-8.5), while some water samples were found to exceed the
      allowed WHO limit for total dissolved solids (TDSs) in drinking water. Results
      showed that concentrations of the heavy metals vary significantly between the 44
      samples. Results also showed that the concentration of five heavy metals (Cr, Mn,
      Ni, Ag, and Pb) is higher than the WHO limits for these heavy metals in drinking
      water. Overall, our findings revealed that harvested rainwater used for drinking
      of this part of south West Bank is contaminated with heavy metals that might
      affect human health. 

PMID- 25063535
TI  - Long-term chemical and biological improvement in an acid mine drainage-impacted
      watershed.
AB  - Acid mine drainage (AMD) is a common result of coal and metal mining worldwide
      caused by weathering of metal sulfides exposed during mining. AMD typically
      results in low-pH, high-metal, high-conductivity water that does not support
      aquatic life. Chemical water quality improvement does not necessarily lead to
      rapid biological recovery. Little Raccoon Creek, a major tributary to Raccoon
      Creek in the Western Allegheny Plateau of Ohio, drains 401 km(2), has a legacy of
      AMD that stems from mining activities over more than a century. Since 1999, seven
      major passive treatments systems have been installed in the watershed to a total
      of over $6.5 million. This study analyzes the hourly water quality data collected
      at a United States Geological Survey gage station alongside trends in fish and
      macroinvertebrate communities. Both fish and macroinvertebrate communities have
      shown a statistically significant improvement in the lower reaches of Little
      Raccoon Creek since treatment began. Long-term chemical monitoring shows a
      significant increase in pH, but no significant change in conductivity. The
      conductivity data is well correlated with sulfate concentrations and discharge,
      while the pH is well correlated with net  alkalinity data, but not with
      discharge. Significant investment in passive treatment systems and land
      reclamation has decreased the percent occurrence of pH measurements below the
      target of 6.5 and has led to recovery of both fish and macroinvertebrate
      communities in the downstream reaches of Little Raccoon Creek. Long-term
      monitoring has proven to be a valuable tool to assess success of a high-cost
      remediation program. 

PMID- 25063536
TI  - Pneumocephalus: an unusual case of postoperative seizure after intradural spine
      surgery.

PMID- 25063537
TI  - Serum uric acid does not predict incident metabolic syndrome in a population with
      high prevalence of obesity.
AB  - AIM: To evaluate whether uric acid (UA) predicts 4-yr incidence of metabolic
      syndrome (MetS) in non-diabetic participants of the Strong Heart Study (SHS)
      cohort. METHODS AND RESULTS: In this population-based prospective study we
      analyzed 1499 American Indians (890 women), without diabetes or MetS, controlled
      during the 4th SHS exam and re-examined 4 years later during the 5th SHS exam.
      Participants were divided into sex-specific tertiles of UA and the first two
      tertiles (group N) were compared with the third tertile (group H). Body mass
      index (BMI = 28.3 +/- 7 vs. 31.1 +/- 7 kg/m(2)), fat-free mass (FFM = 52.0 +/- 14
      vs. 54.9 +/- 11 kg), waist-to-hip ratio, HOMA-IR (3.66 vs. 4.26), BP and indices
      of inflammation were significantly higher in group H than in group N (all p <
      0.001). Incident MetS at the time of the 5th exam was more frequent in group H
      than group N (35 vs. 28%, OR 1.44 (95% CI = 1.10-1.91; p < 0.01). This
      association was still significant (OR = 1.13, p = 0.04) independently of family
      relatedness, sex, history of hypertension, HOMA-IR, central adiposity and renal
      function, but disappeared when fat-free mass was included in the model.
      CONCLUSIONS: In the SHS, UA levels are associated to parameters of insulin
      resistance and to indices of inflammation. UA levels, however, do not predict
      incident MetS independently of the initial obesity-related increased FFM.

PMID- 25063538
TI  - Dietary non-enzymatic antioxidant capacity and the risk of myocardial infarction:
      a case-control study in Italy.
AB  - BACKGROUND AND AIMS: Oxidative processes have been related to atherosclerosis,
      but there is scanty information on the role of dietary antioxidants in the
      prevention of acute myocardial infarction (AMI). METHODS AND RESULTS: The
      relationship between non-enzymatic antioxidant capacity (NEAC) and the risk of
      nonfatal AMI was investigated in a case-control study conducted in Milan, Italy,
      between 1995 and 2003. Cases were 760 patients below 75 years with a first
      episode of AMI and controls were 682 patients admitted to hospitals for acute
      conditions, who completed an interviewer-administered food frequency
      questionnaire, tested for validity and reproducibility. NEAC (excluding coffee)
      was measured using Italian food composition tables in terms of ferric reducing
      antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total
      radical-trapping antioxidant parameter (TRAP). The odds ratios (OR) of AMI, and
      the corresponding 95% confidence intervals (CI), were obtained by multiple
      logistic regression models including terms for main risk factors of AMI and total
      energy intake. NEAC was inversely related with the risk of AMI. The ORs for the
      highest quintile compared with the lowest one were 0.41 (95% CI, 0.27-0.63) for
      FRAP, 0.42 (95% CI, 0.27-0.65) for TEAC and 0.41 (95% CI, 0.27-0.62) for TRAP,
      with significant trends in risk. The inverse relationship was apparently stronger
      in women and in subjects aged >= 60 years. CONCLUSIONS: Our results support a
      favorable role of dietary NEAC in the prevention of AMI, and encourage a high
      consumption of fruit and vegetables and a moderate consumption of wine and whole
      cereals.

PMID- 25063539
TI  - Fish and omega-3 fatty acid intake in relation to circulating fibroblast growth
      factor 23 levels in renal transplant recipients.
AB  - BACKGROUND AND AIMS: A high circulating fibroblast growth factor 23 (FGF23) level
      is an independent risk factor for cardiovascular mortality in renal transplant
      recipients and the general population. N-3 fatty acids eicosapentaenoic (EPA) and
      docosahexaenoic acid (DHA) may contribute to cardiovascular risk reduction. We
      investigated whether fish and EPA-DHA intake are related to FGF23 levels in renal
      transplant recipients. METHODS AND RESULTS: We performed a cross-sectional
      analysis in 619 stable renal transplant recipients (mean age 53 years, 57% male,
      estimated glomerular filtration rate [eGFR] 53 +/- 20 mL/min/1.73 m(2)). Dietary
      intake was assessed by a 177-item food frequency questionnaire. Serum intact
      FGF23 was measured by ELISA. We examined differences in FGF23 levels across
      categories of fish and EPA-DHA intake using analysis of variance models adjusted
      for age, sex, dietary and lifestyle factors and key determinants of FGF23.
      Patients consumed on average 15 g of fish and 139 mg EPA-DHA/day. Median FGF23
      was 62 pg/mL (IQR 43-98 pg/mL). Higher dietary EPA-DHA and fish intake were
      associated with lower serum FGF23 levels. Subgroup analyses revealed that
      particularly in patients with reduced renal function (eGFR <60 mL/min/1.73 m(2)),
      adjusted FGF23 levels (114, 79, 75 pg/mL, P = 0.0001) were inversely associated
      with tertiles of EPA-DHA intake. Similarly, we observed an inverse association
      between fish consumption and serum FGF23 levels in adjusted analyses. CONCLUSION:
      A higher intake of fish and dietary n-3 fatty acids (EPA-DHA) is related to lower
      circulating FGF23 levels in renal transplant recipients. Further research is
      needed to assess the causality of this association and the clinical implications.

PMID- 25063540
TI  - Latent TB infection in newly diagnosed lung cancer patients - A multicenter
      prospective observational study.
AB  - OBJECTIVES: Lung cancer and tuberculosis (TB) share common risk factors and are
      associated with high morbidity and mortality. Coexistence of lung cancer and TB
      were reported in previous studies, with uncertain pathogenesis. The association
      between lung cancer and latent TB infection (LTBI) remains to be explored.
      METHODS: Newly diagnosed, treatment-naive lung cancer patients were prospectively
      enrolled from four referral medical centers in Taiwan. The presence of LTBI was
      determined by QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic characteristics
      and cancer-related factors associated with LTBI were investigated. The survival
      status was also analyzed according to the status of LTBI. RESULTS: A total of 340
      lung cancer patients were enrolled, including 96 (28.2%) LTBI, 214 (62.9%) non
      LTBI, and 30 (8.8%) QFT-GIT results-indeterminate cases. Non-adenocarcinoma cases
      had higher proportion of LTBI than those of adenocarcinoma, especially in
      patients with younger age. In multivariate analysis, COPD (OR 2.41, 95% CI 1.25
      4.64), fibrocalcified lesions on chest radiogram (OR 2.73, 95% CI 1.45-5.11), and
      main tumor located in typical TB areas (OR 2.02, 95% CI 1.15-3.55) were
      independent clinical predictors for LTBI. Kaplan-Meier survival analysis
      demonstrated patients with indeterminate QFT-GIT results had significantly higher
      1-year all-cause mortality than those with LTBI (p<0.001) and non-LTBI (p=0.003).
      In multivariate analysis, independent predictors for 1-year all-cause mortality
      included BMI<18.5 (HR 2.09, 95% CI 1.06-4.14, p=0.033), advanced stage of lung
      cancer (RR 7.76, 95% CI 1.90-31.78, p=0.004), and indeterminate QFT-GIT results
      (RR 2.40, 95% CI 1.27-4.54, p=0.007). CONCLUSIONS: More than one-quarter of newly
      diagnosed lung cancer patients in Taiwan have LTBI. The independent predictors
      for LTBI include COPD, fibrocalcified lesions on chest radiogram, and main tumor
      located in typical TB areas. The survival rate is comparable between LTBI and non
      LTBI cases. However, indeterminate QFT-GIT result was an independent predictor
      for all-cause mortality in lung cancer patients.

PMID- 25063541
TI  - The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study.
AB  - BACKGROUND: Nationally, symptomatic heart failure affects 1.5-2% of Canadians,
      incurs $3 billion in hospital costs annually and the global burden is expected to
      double in the next 1-2 decades. The current one-year mortality rate after
      diagnosis of heart failure remains high at >25%. Consequently, new therapeutic
      strategies need to be developed for this debilitating condition. METHODS/DESIGN:
      The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to
      develop novel diagnostic, therapeutic and prognostic approaches to patients with
      heart failure with preserved ejection fraction. We hypothesize that novel imaging
      techniques and biomarkers will aid in describing heart failure with preserved
      ejection fraction. Furthermore, the development of new diagnostic criteria will
      allow us to: 1) better define risk factors associated with heart failure with
      preserved ejection fraction; 2) elucidate clinical, cellular and molecular
      mechanisms involved with the development and progression of heart failure with
      preserved ejection fraction; 3) design and test new therapeutic strategies for
      patients with heart failure with preserved ejection fraction. Additionally,
      Alberta HEART provides training and education for enhancing translational
      medicine, knowledge translation and clinical practice in heart failure. This is a
      prospective observational cohort study of patients with, or at risk for, heart
      failure. Patients will have sequential testing including quality of life and
      clinical outcomes over 12 months. After that time, study participants will be
      passively followed via linkage to external administrative databases. Clinical
      outcomes of interest include death, hospitalization, emergency department visits,
      physician resource use and/or heart transplant. Patients will be followed for a
      total of 5 years. DISCUSSION: Alberta HEART has the primary objective to define
      new diagnostic criteria for patients with heart failure with preserved ejection
      fraction. New criteria will allow for targeted therapies, diagnostic tests and
      further understanding of the patients, both at-risk for and with heart failure.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT02052804.

PMID- 25063542
TI  - Smad7 enhances ATM activity by facilitating the interaction between ATM and Mre11
      Rad50-Nbs1 complex in DNA double-strand break repair.
AB  - Genomic instability is one of the representative causes in genetic disorder,
      where the proper cellular response to DNA damage is essential in maintaining
      genomic stability. ATM and the Mre11-Rad50-Nbs1 (MRN) complex play critical roles
      in the cellular response to DNA damage such as DNA double-strand break (DSB). In
      this study, we report that Smad7 is indispensible in DNA damage response as a
      novel component of MRN complex. Smad7 enhances cell survival against DNA damage
      by accelerating ATM dependent DNA repair signaling. In Smad7-deficient mouse
      embryonic fibroblast cells, the loss of Smad7 decreases ATM activation and
      inhibits recruitment of ATM to the sites of DSBs. Smad7 interacts with Nbs1, a
      member of MRN complex, and enhances the interaction between ATM and Nbs1 upon DNA
      damage response, leading to phosphorylation of downstream substrates. Ectopic
      expression of Smad7 in the skin of mice enhances the phosphorylation of ATM upon
      X-irradiation. We found that effect of Smad7 on enhancing DNA repair is
      independent of its inhibitory activity of TGF-beta signaling. Taken together, our
      results highlight a critical function of Smad7 in DSB response and establish the
      novel mechanism in which Smad7 facilitates the recruitment of ATM to the MRN
      complex through direct interaction with Nbs1. 

PMID- 25063543
TI  - Immobilization contributes to exaggerated neuropeptide signaling, inflammatory
      changes, and nociceptive sensitization after fracture in rats.
AB  - A tibia fracture cast immobilized for 4 weeks can induce exaggerated substance P
      and calcitonin gene-related peptide signaling and neuropeptide-dependent
      nociceptive and inflammatory changes in the hind limbs of rats similar to those
      seen in complex regional pain syndrome (CRPS). Four weeks of hind limb cast
      immobilization can also induce nociceptive and vascular changes resembling CRPS.
      To test our hypothesis that immobilization alone could cause exaggerated
      neuropeptide signaling and inflammatory changes, we tested 5 cohorts of rats: 1)
      controls; 2) tibia fracture and hind limb casted; 3) hind limb casted, no
      fracture; 4) tibia fracture with intramedullary pinning, no cast; and 5) tibia
      fracture with intramedullary pinning and hind limb casting. After 4 weeks, the
      casts were removed and hind limb allodynia, unweighting, warmth, edema, sciatic
      nerve neuropeptide content, cutaneous and spinal cord inflammatory mediator
      levels, and spinal c-Fos activation were measured. After fracture with casting,
      there was allodynia, unweighting, warmth, edema, increased sciatic nerve
      substance P and calcitonin gene-related peptide, increased skin neurokinin 1
      receptors and keratinocyte proliferation, increased inflammatory mediator
      expression in the hind paw skin (tumor necrosis factor-alpha, interleukin [IL]
      1beta, IL-6, nerve growth factor) and cord (IL-1beta, nerve growth factor), and
      increased spinal c-Fos activation. These same changes were observed after cast
      immobilization alone, except that spinal IL-1beta levels were not increased.
      Treating cast-only rats with a neurokinin 1 receptor antagonist inhibited
      development of nociceptive and inflammatory changes. Four weeks after fracture
      with pinning, all nociceptive and vascular changes had resolved and there were no
      increases in neuropeptide signaling or inflammatory mediator expression.
      PERSPECTIVE: Collectively, these data indicate that immobilization alone
      increased neuropeptide signaling and caused nociceptive and inflammatory changes
      similar to those observed after tibia fracture and casting, and that early
      mobilization after fracture with pinning inhibited these changes. Early limb
      mobilization after fracture may prevent the development of CRPS.

PMID- 25063544
TI  - [New aspects in the therapy of multiple sclerosis and optic neuritis].
AB  - BACKGROUND: Despite the success of recently introduced immunomodulatory
      therapies, multiple sclerosis and its ophthalmic manifestation as optic neuritis
      lead to irreversible axonal degeneration. Hence, it would be desirable to apply a
      neuroprotective therapy in parallel. RESULTS AND DISCUSSION: We identified
      erythropoietin as an available and approved drug exerting neuroprotective effects
      in addition to its hematopoetic action. After several successful preclinical
      experiments, the pilot trial VISION PROTECT has shown that 33,000 IU
      erythropoietin, given intravenously on 3 consecutive days, preserves the retinal
      nerve fibre layer to a significant extent. This therapy will now be evaluated in
      a full scale and adequately powered trial to challenge this hypothesis. The TONE
      trial (Treatment of Optic Neuritis with Erythropoietin, NCT01962571) is a
      multicentric, prospective, double-blinded, clinical trial evaluating the same
      therapeutic regimen primarily with regard to thickness of the retinal nerve fibre
      layer and low contrast visual acuity.

PMID- 25063545
TI  - [Hepatic abnormality].

PMID- 25063547
TI  - Letter to the Editor: critical-sized bone defect in sheep model.

PMID- 25063546
TI  - Juvenile Paget's disease with heterozygous duplication within TNFRSF11A encoding
      RANK.
AB  - Mendelian disorders of RANKL/OPG/RANK signaling feature the extremes of aberrant
      osteoclastogenesis and cause either osteopetrosis or rapid turnover skeletal
      disease. The patients with autosomal dominant accelerated bone remodeling have
      familial expansile osteolysis, early-onset Paget's disease of bone, expansile
      skeletal hyperphosphatasia, or panostotic expansile bone disease due to
      heterozygous 18-, 27-, 15-, and 12-bp insertional duplications, respectively,
      within exon 1 of TNFRSF11A that encodes the signal peptide of RANK. Juvenile
      Paget's disease (JPD), an autosomal recessive disorder, manifests extremely fast
      skeletal remodeling, and is usually caused by loss-of-function mutations within
      TNFRSF11B that encodes OPG. These disorders are ultra-rare. A 13-year-old
      Bolivian girl was referred at age 3years. One femur was congenitally short and
      curved. Then, both bowed. Deafness at age 2years involved missing ossicles and
      eroded cochleas. Teeth often had absorbed roots, broke, and were lost.
      Radiographs had revealed acquired tubular bone widening, cortical thickening, and
      coarse trabeculation. Biochemical markers indicated rapid skeletal turnover.
      Histopathology showed accelerated remodeling with abundant osteoclasts. JPD was
      diagnosed. Immobilization from a femur fracture caused severe hypercalcemia that
      responded rapidly to pamidronate treatment followed by bone turnover marker and
      radiographic improvement. No TNFRSF11B mutation was found. Instead, a unique
      heterozygous 15-bp insertional tandem duplication (87dup15) within exon 1 of
      TNFRSF11A predicted the same pentapeptide extension of RANK that causes expansile
      skeletal hyperphosphatasia (84dup15). Single nucleotide polymorphisms in
      TNFRSF11A and TNFRSF11B possibly impacted her phenotype. Our findings: i) reveal
      that JPD can be associated with an activating mutation within TNFRSF11A, ii)
      expand the range and overlap of phenotypes among the Mendelian disorders of RANK
      activation, and iii) call for mutation analysis to improve diagnosis,
      prognostication, recurrence risk assessment, and perhaps treatment selection
      among the monogenic disorders of RANKL/OPG/RANK activation. 

PMID- 25063548
TI  - Resistance to thyroid hormone due to mutations in the THRB gene impairs bone mass
      and affects calcium and phosphorus homeostasis.
AB  - CONTEXT: Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced
      tissue responsiveness to thyroid hormone, which is usually due to mutations in
      the thyroid hormone receptor beta gene (THRB). Few studies have been conducted to
      investigate bone and mineral metabolism in RTH. OBJECTIVE: The objective of the
      study was to evaluate the clinical and biochemical parameters related to bone and
      mineral metabolism in RTH due to mutations in the THRB gene (RTHbeta). DESIGN AND
      PARTICIPANTS: We conducted a cross-sectional study on 14 patients with RTHbeta
      (RTHG), eight adults and six children, and 24 control subjects (CG). OUTCOMES:
      Serum measures included total calcium (TCa), inorganic phosphate (iP), alkaline
      phosphatase (AP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD),
      osteocalcin (OC), carboxyterminal telopeptide (CTX), and fibroblast growth factor
      23 (FGF-23). We estimated the renal threshold phosphate concentration (TmPO4/GFR)
      and assessed bone mass using dual X-ray absorptiometry. RESULTS: Adults and
      children with RTH showed higher serum levels of TCa than controls (P=.029 and,
      P=.018 respectively). However, only children with RTH exhibited lower serum
      levels of iP than controls (P=.048). FGF-23 was higher in RTHbeta children
      (P=.04). RTHbeta adults had lower whole-body (P=.01) and lumbar spine (P=.01)
      bone mineral density than control subjects. The same pattern was observed when
      the results were expressed as Z-scores between groups, with a lower value in RTHG
      than in CG for the lumbar spine of adults (P=.03). No difference was observed
      between groups in PTH, 25OHD, AP, OC, and CTX. CONCLUSION: Biochemical
      abnormalities are seen in children with RTH (Low iP, high FGF23), while high
      calcium (with normal UCa) is seen in RTH subjects of all ages, and later on, in
      adult life, low BMD is seen. Considering that the TRalpha1 isoform is the
      predominant TR in the skeleton, we hypothesize that probably these patients may
      exhibit enhanced calcium flux from bone to circulation. Our data represent a
      challenge for new studies to unveil the control of calcium and phosphorus
      homeostasis and fracture risk in these patients.

PMID- 25063549
TI  - Rapid and specific detection of section Fumigati and Aspergillus fumigatus in
      human samples using a new multiplex real-time PCR.
AB  - Invasive aspergillosis is an opportunistic infection caused primarily by
      Aspergillus fumigatus. However, other common fungal pathogens belonging to
      section Fumigati are often misidentified as A. fumigatus. Thus, we have developed
      a multiplex real-time PCR (qPCR) assay with primers and specific TaqMan probes
      based on internal transcribed spacer regions or benA gene to discriminate, in
      less than 3 h, species of section Fumigati and, specifically, A. fumigatus. The
      multiplex qPCR showed a limit of detection of 20 and 50 fg of DNA for section
      Fumigati and A. fumigatus, respectively. Moreover, it enabled detection of a
      single germinated conidia. The inclusion of some PCR facilitators together with
      the dilution of samples makes it possible to completely avoid PCR inhibitions in
      all bronchoalveolar lavage (BAL) samples assayed. This technique may be a useful
      complementary tool in the diagnosis of invasive pulmonary aspergillosis caused by
      A. fumigatus using BAL fluid. 

PMID- 25063550
TI  - Are we done with dose-intense temozolomide in recurrent glioblastoma?

PMID- 25063552
TI  - Novel divergent nidovirus in a python with pneumonia.
AB  - The order Nidovirales contains large, enveloped viruses with a non-segmented
      positive-stranded RNA genome. Nidoviruses have been detected in man and various
      animal species, but, to date, there have been no reports of nidovirus in
      reptiles. In the present study, we describe the detection, characterization,
      phylogenetic analyses and disease association of a novel divergent nidovirus in
      the lung of an Indian python (Python molurus) with necrotizing pneumonia.
      Characterization of the partial genome (>33 000 nt) of this virus revealed
      several genetic features that are distinct from other nidoviruses, including a
      very large polyprotein 1a, a putative ribosomal frameshift signal that was
      identical to the frameshift signal of astroviruses and retroviruses and an
      accessory ORF that showed some similarity with the haemagglutinin-neuraminidase
      of paramyxoviruses. Analysis of genome organization and phylogenetic analysis of
      polyprotein 1ab suggests that this virus belongs to the subfamily Torovirinae.
      Results of this study provide novel insights into the genetic diversity within
      the order Nidovirales.

PMID- 25063553
TI  - A model integration approach linking signalling and gene-regulatory logic with
      kinetic metabolic models.
AB  - Systems biology has to increasingly cope with large- and multi-scale biological
      systems. Many successful in silico representations and simulations of various
      cellular modules proved mathematical modelling to be an important tool in gaining
      a solid understanding of biological phenomena. However, models spanning different
      functional layers (e.g. metabolism, signalling and gene regulation) are still
      scarce. Consequently, model integration methods capable of fusing different types
      of biological networks and various model formalisms become a key methodology to
      increase the scope of cellular processes covered by mathematical models. Here we
      propose a new integration approach to couple logical models of signalling or/and
      gene-regulatory networks with kinetic models of metabolic processes. The
      procedure ends up with an integrated dynamic model of both layers relying on
      differential equations. The feasibility of the approach is shown in an
      illustrative case study integrating a kinetic model of central metabolic pathways
      in hepatocytes with a Boolean logical network depicting the hormonally induced
      signal transduction and gene regulation events involved. In silico simulations
      demonstrate the integrated model to qualitatively describe the physiological
      switch-like behaviour of hepatocytes in response to nutritionally regulated
      changes in extracellular glucagon and insulin levels. A simulated failure mode
      scenario addressing insulin resistance furthermore illustrates the
      pharmacological potential of a model covering interactions between signalling,
      gene regulation and metabolism. 

PMID- 25063551
TI  - Early dexamethasone treatment induces placental apoptosis in sheep.
AB  - Glucocorticoid treatment given in late pregnancy in sheep resulted in altered
      placental development and function. An imbalance of placental survival and
      apoptotic factors resulting in an increased rate of apoptosis may be involved. We
      have now investigated the effects of dexamethasone (DEX) in early pregnancy on
      binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of
      these responses. Pregnant ewes carrying singleton fetuses (n = 105) were
      randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 49,
      intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at
      40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and
      140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic
      (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax,
      p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC
      numbers and apoptotic markers were restored to normal. In males, ovine placental
      lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG
      significantly decreased compared to controls. In contrast to females, these
      changes were independent of altered BNC numbers or apoptotic markers. Early DEX
      was associated with sex-specific, transient alterations in BNC numbers, which may
      contribute to changes in placental and fetal development. Furthermore, in
      females, altered placental apoptosis markers may be involved. 

PMID- 25063554
TI  - A hazard ratio was estimated by a ratio of median survival times, but with
      considerable uncertainty.
AB  - OBJECTIVES: To evaluate the empirical concordance between the hazard ratio (HR)
      and the median ratio (MR) in survival cancer studies. STUDY DESIGN AND SETTING:
      We selected all cancer survival articles from the New England Journal of Medicine
      published between 2000 and 2010. The qualitative concordance was estimated by the
      proportion of measured pairs in which the treatment effects for the MR and HR are
      in the same direction. The quantitative concordance was assessed through (1) the
      mean difference between the logarithms of the measures, (2) the Lin coefficient,
      and (3) the Bland-Altman plot. RESULTS: We retrieved 106 measured pairs (HR-MR)
      corresponding to 54 articles. Concordance was high, at both the qualitative (99
      of 106, 93.4%) and quantitative levels (mean MR-to-HR ratio, 1.01; 95% confidence
      interval: 0.95, 1.06). However, the 95% Bland-Altman discordance limits indicate
      that the MR can be up to 50% higher or 50% lower than the HR. CONCLUSION: The
      average concordance allows trialists to approximate HR from MR to determine
      sample size. However, the discordance limits are too great to consider that both
      measures are interchangeable. The actual policy to report HR only is not enough.
      Our results emphasize the need to attach descriptive survival measures to the HR.

PMID- 25063555
TI  - The 2 * 2 cluster randomized controlled factorial trial design is mainly used for
      efficiency and to explore intervention interactions: a systematic review.
AB  - OBJECTIVES: To describe the health care settings, purposes, and study reporting
      quality of the 2 * 2 cluster randomized controlled factorial trial design. STUDY
      DESIGN AND SETTING: This study is a systematic review. We searched Medline,
      Embase, Cochrane Library, and Web of Knowledge for articles published up to May
      2012. Cluster randomized controlled 2 * 2 factorial trials in health, evaluating
      at least one complex intervention, were included. Two authors independently
      reviewed and extracted data from the studies. RESULTS: Twenty-nine studies
      covering a wide range of clinical areas and health care settings were included.
      The cluster design was mostly used to minimize contamination. The factorial
      design was mostly used to assess the effects of two interventions in the same
      study and to explore interactions between interventions. However, although most
      studies explored the presence or absence of intervention interactions, they were
      often either not sufficiently powered to detect any interactions or did not
      provide information on whether the study was sufficiently powered to detect any
      interactions. There was a considerable variability in the reporting of a number
      of study characteristics and methodological aspects. Study quality was also
      variable within and across studies. CONCLUSION: The design has been used in a
      wide range of health care settings and clinical areas to minimize contamination,
      assess the effects of two interventions in the same study, and explore
      intervention interactions. There is need for improvement on and guidelines for
      the reporting of factorial trials.

PMID- 25063557
TI  - When is a health-care quality indicator ready to use?

PMID- 25063556
TI  - Distinct trajectories of multimorbidity in primary care were identified using
      latent class growth analysis.
AB  - OBJECTIVES: To investigate the use of latent class growth analysis (LCGA) in
      understanding onset and changes in multimorbidity over time in older adults.
      STUDY DESIGN AND SETTING: This study used primary care consultations for 42
      consensus-defined chronic morbidities over 3 years (2003-2005) by 24,615 people
      aged >50 years at 10 UK general practices, which contribute to the Consultations
      in Primary Care Archive database. Distinct groups of people who had similar
      progression of multimorbidity over time were identified using LCGA. These derived
      trajectories were tested in another primary care consultation data set with
      linked self-reported health status. RESULTS: Five clusters of people representing
      different trajectories were identified: those who had no recorded chronic
      problems (40%), those who developed a first chronic morbidity over 3 years (10%),
      a developing multimorbidity group (37%), a group with increasing number of
      chronic morbidities (12%), and a multi-chronic group with many chronic
      morbidities (1%). These trajectories were also identified using another
      consultation database and associated with self-reported physical and mental
      health. CONCLUSION: There are distinct trajectories in the development of
      multimorbidity in primary care populations, which are associated with poor
      health. Future research needs to incorporate such trajectories when assessing
      progression of disease and deterioration of health.

PMID- 25063558
TI  - Systematic overview finds variation in approaches to investigating and reporting
      on sources of heterogeneity in systematic reviews of diagnostic studies.
AB  - OBJECTIVES: To examine how authors explore and report on sources of heterogeneity
      in systematic reviews of diagnostic accuracy studies. STUDY DESIGN AND SETTING: A
      cohort of systematic reviews of diagnostic tests was systematically identified.
      Data were extracted on whether an exploration of the sources of heterogeneity was
      undertaken, how this was done, the number and type of potential sources explored,
      and how results and conclusions were reported. RESULTS: Of the 65 systematic
      reviews, 12 did not perform a meta-analysis and eight of these gave heterogeneity
      between studies as a reason. Of the 53 reviews containing a meta-analysis, 40
      explored potential sources of heterogeneity in a formal manner and 27 identified
      at least one source of heterogeneity. The reviews not investigating heterogeneity
      were smaller than those that did (median [interquartile range {IQR}], 8 [5-15]
      vs. 14 [11-19] primary studies). Twelve reviews performed a sensitivity analysis,
      25 stratified analyses, and 19 metaregression. Many sources of heterogeneity were
      explored compared with the number of primary studies in a meta-analysis (median
      ratio, 1:5). Review authors placed importance on the exploration of sources of
      heterogeneity; 37 mentioned the exploration or the findings thereof in the
      abstract or conclusion of the main text.results CONCLUSION: Methods for
      investigating sources of heterogeneity varied widely between reviews. Based on
      our findings of the review, we made suggestions on what to consider and report on
      when exploring sources of heterogeneity in systematic reviews of diagnostic
      studies.

PMID- 25063559
TI  - Reprint of "Biogenesis and adhesion of type 1 and P pili".
AB  - BACKGROUND: Uropathogenic Escherichia coli (UPEC) cause urinary tract infections
      (UTIs) in approximately 50% of women. These bacteria use type 1 and P pili for
      host recognition and attachment. These pili are assembled by the chaperone-usher
      pathway of pilus biogenesis. SCOPE OF REVIEW: The review examines the biogenesis
      and adhesion of the UPEC type 1 and P pili. Particular emphasis is drawn to the
      role of the outer membrane usher protein. The structural properties of the
      complete pilus are also examined to highlight the strength and functionality of
      the final assembly. MAJOR CONCLUSIONS: The usher orchestrates the sequential
      addition of pilus subunits in a defined order. This process follows a subunit
      incorporation cycle which consists of four steps: recruitment at the usher N
      terminal domain, donor-strand exchange with the previously assembled subunit,
      transfer to the usher C-terminal domains and translocation of the nascent pilus.
      Adhesion by the type 1 and P pili is strengthened by the quaternary structure of
      their rod sections. The rod is endowed with spring-like properties which provide
      mechanical resistance against urine flow. The distal adhesins operate differently
      from one another, targeting receptors in a specific manner. The biogenesis and
      adhesion of type 1 and P pili are being therapeutically targeted, and efforts to
      prevent pilus growth or adherence are described. GENERAL SIGNIFICANCE: The
      combination of structural and biochemical study has led to the detailed
      mechanistic understanding of this membrane spanning nano-machine. This can now be
      exploited to design novel drugs able to inhibit virulence. This is vital in the
      present era of resurgent antibiotic resistance. This article is part of a Special
      Issue entitled Structural biochemistry and biophysics of membrane proteins.

PMID- 25063561
TI  - Taking care of patients with brain tumor-related epilepsy: results from an
      Italian survey.
AB  - To date, no data have been published in literature regarding either a "model" or
      systematic approach to caring for patients with brain tumor-related epilepsy
      (BTRE). In Italy, there are numerous dedicated centers for epilepsy. STUDY AIMS:
      to investigate how many BTRE patients were followed by these specialized centers,
      independent of histological grade; to have a national snapshot of the range of
      care issues concerning these patients, with surveys completed by Italian centers
      adhering to the Italian League Against Epilepsy (LICE) study group for BTRE. Each
      participating Italian center received a survey requesting: description of
      organizational structure/service model for diagnosis and treatment of epilepsy;
      number of patients followed (from 1/2010 to 12/2011); services offered, within
      the same institution or in close proximity; degree of access to colleagues from
      other disciplines for discussion of cases, with indication of departments/areas
      of specialization were sought. Thirty out of the 35 centers adhering to LICE
      study group completed the survey indicating total of 2,528 patients with BTRE had
      been treated with 940 new patients/year. Data regarding the care model, service
      offerings, referral sources were collected. This study is a first collaborative
      project of epilepsy centers throughout Italy, aimed at collecting data on a
      national scale. Results indicate: (1) 2,528 patients had been followed by
      participating centers and account for 21 % of estimated patients with BTRE in
      Italy (2) difficulties in organizing meetings with other specialists (e.g. for
      discussion of cases/patient briefings); (3) need for multidisciplinary
      integration with other specialists as a priority area for intervention.

PMID- 25063560
TI  - Intravenous thrombolysis for minor stroke and rapidly improving symptoms: a
      quantitative overview.
AB  - Minor stroke and rapidly improving symptoms (MRIS) are usually excluded from
      intravenous thrombolysis (IVT) considering a possible benign prognosis and
      potential bleeding risk. However, its risk-benefit profile from IVT has not been
      fully illustrated. We searched PubMed for articles published up to December 2013
      and included papers focused on the functional outcome of MRIS after IVT. The
      primary analysis was a comparison of the prognosis of MRIS after IVT versus non
      minor stroke with IVT and MRIS without IVT, respectively. For safety analysis,
      the rates of symptomatic intracranial hemorrhage (SICH) and mortality were
      compared. Statistic calculation was conducted using the RevMan5.1 software. A
      total of 13 citations encompassing 2905 MRIS cases were included. Favorable
      discharge outcome was more frequent in non-thrombolysed MRIS than thrombolysed
      MRIS with an odds ratio (OR) of 0.50 (95 % CI, 0.25-0.97), while no difference
      was noted in the outcome after 3 months (OR 0.99; 95 % CI, 0.74-1.34). Compared
      with non-minor stroke, MRIS had nearly 4 times more chance to have a favorable 3
      month outcome after IVT, accompanied with a lower rate of SICH (pooled rate, 3.68
      % versus 5.77 %; OR 0.57; 95 % CI, 0.39-0.84). Mortality was not significantly
      different for MRIS with or without IVT (OR 1.21; 95 % CI, 0.54-2.72) in the
      included population, but was still much less than non-minor stroke after IVT (OR
      0.16; 95 % CI, 0.09-0.31). MRIS patients seem not to benefit from IVT in the
      short-term and 3-month outcomes due to increasing early hazards. Compared with
      non-minor stroke, MRIS with IVT suffers a significantly lower risk of SICH and
      death.

PMID- 25063563
TI  - First discovery of postcranial bones of Ouranopithecus macedoniensis (Primates,
      Hominoidea) from the late Miocene of Macedonia (Greece).
AB  - Two well preserved phalanges, one proximal and one intermediate, are identified
      and described. They constitute the first postcrania ever described of
      Ouranopithecus macedoniensis (Primates, Hominoidea) from the late Miocene
      locality of Ravin de la Pluie (RPl), Macedonia (Greece). They are isolated
      specimens, and the only ones known for their genus. The hypotheses that these
      specimens derive either from the hand or from the foot were tested. Comparisons
      with living apes of known positional behaviour were made to assess the functional
      signal in these specimens. The proximal phalanx, either manual or pedal, closely
      matches the proximal phalanges of terrestrial quadrupedal primates or the bipedal
      primate Homo. With respect to the intermediate phalanx we show that it closely
      matches phalanges of quadrupedal terrestrial primates. The terrestriality of
      Ouranopithecus, here reconstructed from phalangeal remains, is in agreement with
      our previous results of dental studies (thick check teeth enamel and microwear
      pattern of incisors and molars), which indicate that it was a hard object feeder
      living near the ground. 

PMID- 25063562
TI  - Reference particles for toxicological studies of wood combustion: formation,
      characteristics, and toxicity compared to those of real wood combustion
      particulate mass.
AB  - Multiple studies show that particulate mass (PM) generated from incomplete wood
      combustion may induce adverse health issues in humans. Previous findings have
      shown that also the PM from efficient wood combustion may induce enhanced
      production of reactive oxygen species (ROS), inflammation, and cytotoxicity in
      vitro and in vivo. Underlying factors of these effects may be traced back to
      volatile inorganic transition metals, especially zinc, which can be enriched in
      the ultrafine fraction of biomass combustion particulate emission. In this study,
      nanoparticles composed of potassium, sulfur, and zinc, which are the major
      components forming inorganic fine PM, were synthesized and tested in vitro. In
      addition, in vitro toxicity of PM from efficient combustion of wood chips was
      compared with that of the synthesized particles. Cytotoxicity, cell cycle arrest,
      ROS generation, and tumor necrosis factor alpha release were related to zinc
      concentration in PM. Potassium sulfate and potassium carbonate did not induce
      toxic responses. In light of the provided data, it can be concluded that zinc,
      enriched in wood combustion emissions, caused the toxicity in all of the measured
      end points. 

PMID- 25063564
TI  - A morphometric re-assessment of BOU-VP-16/1 from Herto, Ethiopia.

PMID- 25063565
TI  - Possible change in dental morphology in Gigantopithecus blacki just prior to its
      extinction: evidence from the upper premolar enamel-dentine junction.

PMID- 25063566
TI  - Neanderthals from El Salt (Alcoy, Spain) in the context of the latest Middle
      Palaeolithic populations from the southeast of the Iberian Peninsula.
AB  - We present a bioanthropological study of dental remains recovered from El Salt
      Middle Palaeolithic site (Alcoy, Alicante, Spain). The dental remains were found
      in a sedimentary layer representing a calm depositional environment within a
      freshwater spring system. The corresponding archaeological context comprises a
      Middle Palaeolithic faunal and lithic assemblage that represents the last
      documented evidence of human occupation at the site, dating to between 47.2 +/-
      4.4 and 45.2 +/- 3.4 ka (thousands of years ago). This evidence is overlain by an
      archaeologically sterile deposit dated to 44.7 +/- 3.2 ka. Results show that the
      teeth belong to a single juvenile or young adult individual with morphological
      and metric features falling within the Neanderthal range of variability, although
      the considered traits are not taxonomically highly discriminant. The reported
      fossils are representative of the latest Middle Palaeolithic groups in the region
      and may be considered in the ongoing debate on the disappearance of Neanderthals
      and the end of the Middle Palaeolithic. 

PMID- 25063567
TI  - Acheulean technological behaviour in the Middle Pleistocene landscape of Mieso
      (East-Central Ethiopia).
AB  - The Mieso valley is a new paleoanthropological sequence located in East-Central
      Ethiopia. It contains Middle and Upper Pleistocene deposits with fossil and
      lithic assemblages in stratified deposits. This paper introduces the Middle
      Pleistocene archaeological sequence, attributed to the late Acheulean. Low
      density clusters of artefacts suggest short-term use of the landscape by
      Acheulean hominins. In Mieso 31, one of the excavated assemblages, refit sets
      indicate fragmentation of the reduction sequences and enable study of the initial
      stages of biface manufacture. Mieso 7, also a stratified site, is primarily
      characterized by a small concentration of standardized cleavers, and portrays
      another dimension of Acheulean technology, that related to final stages of use
      and discard of large cutting tools. Available radiometric dates place the Mieso
      Acheulean around 212 ka (thousands of years) ago, which would make this sequence
      among the latest evidence of the Acheulean in East Africa, in a time span when
      the Middle Stone Age is already documented in the region.

PMID- 25063568
TI  - Online Diagnosis System: a webserver for analysis of Sanger sequencing-based
      genetic testing data.
AB  - Sanger sequencing is a well-established molecular technique for diagnosis of
      genetic diseases. In these tests, DNA sequencers produce vast amounts of data
      that need to be examined and annotated within a short period of time. To achieve
      this goal, an online bioinformatics platform that can automate the process is
      essential. However, to date, there is no such integrated bioinformatics platform
      available. To fulfill this gap, we developed the Online Diagnosis System (ODS),
      which is a freely available webserver and supports the commonly used file format
      of Sanger sequencing data. ODS seamlessly integrates base calling, single
      nucleotide variation (SNV) identification, and SNV annotation into one single
      platform. It also allows laboratorians to manually inspect the quality of the
      identified SNVs in the final report. ODS can significantly reduce the data
      analysis time therefore allows Sanger sequencing-based genetic testing to be
      finished in a timely manner. ODS is freely available at
      http://sunlab.lihs.cuhk.edu.hk/ODS/. 

PMID- 25063569
TI  - Generation of nonhydrolyzable ubiquitin-histone mimics.
AB  - Histone proteins undergo various types of post-translational modifications (PTMs)
      to regulate dynamic processes in the cell, including replication, transcription
      and DNA damage repair. One type of histone PTM is the attachment of a small
      protein, ubiquitin (Ub). In eukaryotic organisms, a single Ub is attached to
      specific lysine residues of histones H2A and H2B in a modification that, unlike
      many other forms of ubiquitination in the cell, does not signal degradation.
      Instead, both attachment and removal of Ub to these histones has been shown to
      affect gene transcription, pre-mRNA splicing, and DNA damage repair, but the
      mechanisms by which histone ubiquitination governs these processes are not well
      understood. In an effort to identify "readers" of Ub-histones, we developed a
      straightforward crosslinking strategy to generate nonhydrolyzable Ub-histone
      mimics. These mimics were assembled into Ub-histone-containing dimers or
      nucleosomes. We demonstrate that they can be used in pulldown assays to identify
      proteins that differentiate unmodified and ubiquitinated histones. 

PMID- 25063570
TI  - Parents' preferences for seasonal influenza vaccine for their children in Japan.
AB  - In Japan, trivalent inactivated influenza vaccine is the only approved influenza
      vaccine. It is typically administrated by hypodermic injection, and children
      under 13 years of age are recommended to be vaccinated two times during each
      winter season. Live-attenuated influenza vaccine (LAIV) is administered by a
      thimerosal-free nasal spray. If LAIV is approved in the future in Japan, parents
      will have an alternative type of influenza vaccine for their children. This study
      investigated parents' preference for the type of seasonal influenza vaccine for
      their children if alternatives are available. The marginal willingness to pay for
      vaccine benefits was also evaluated. We conducted a discrete choice experiment, a
      quantitative approach that is often used in healthcare studies, in January 2013.
      Respondents were recruited from a registered online survey panel, and parents
      with at least one child under 13 years of age were offered questionnaires. This
      study showed that for seasonal influenza vaccines for their children, parents are
      more likely to value safety, including thimerosal-free vaccines and those with a
      lower risk of adverse events, instead of avoiding the momentary pain from an
      injection. If LAIV is released in Japan, the fact that it is thimerosal-free
      could be an advantage. However, for parents to choose LAIV, they would need to
      accept the slightly higher risk of minor adverse events from LAIV.

PMID- 25063571
TI  - Designing drugs that encourage spinal cord injury healing.
AB  - INTRODUCTION: Spinal cord injury (SCI) occurs within seconds, but host responses
      may take years. Although life expectancy has increased, half of the survivors end
      up as paraplegics, with many indeed as quadriplegics. Host responses may have
      multiple effects ranging from inhibiting inflammation to preventing repair and
      regeneration. Efforts seek to translate exciting results from unsatisfactory
      animal models to humans. AREAS COVERED: The author reviews the current basic and
      translational research for SCI treatment that: i) limits secondary injury; and
      ii) enhances endogenous repair and regeneration. The article provides an emphasis
      on pro-inflammatory factors (TNF-alpha, high-mobility group B protein 1) that are
      targeted to encourage healing. EXPERT OPINION: Research in the coming years needs
      to be directed at therapeutic agents - whether drugs, biologics or biomaterials -
      that encourage repair and regeneration and, at the same time, limit cell death
      and axonal lesions. The author believes that the process of harnessing the power
      of these innate responses will remain the challenge for the future in the quest
      for effective therapeutic options.

PMID- 25063572
TI  - A quality improvement project to improve the rate of early breast milk expression
      in mothers of preterm infants.
AB  - Providing breast milk is challenging for non-nursing mothers of premature
      infants. Early breast milk expression results in successful and longer lactation
      in mothers of very low birth weight (VLBW) infants. This quality improvement
      initiative sought to increase the rate of early milk expression in mothers of
      VLBW infants and increase the proportion of infants receiving maternal breast
      milk (MBM) at 28 days of age and at discharge. Phase 1 (n = 45) occurred between
      April 1, 2012, and August 31, 2012. Phase 2 (n = 58) occurred between September
      1, 2012, and February 28, 2013. Pre-phase 2 actions included increased lactation
      consultant workforce, early lactation consultation, tracking of MBM supply, and
      physician education. Inborn infants < 1500 grams were eligible. Primary outcomes
      were the time of first maternal milk expression (TFME) and infant feeding type at
      28 days of age and at discharge. The median TFME decreased from 9 (25th, 75th
      percentile; 6, 16) hours to 6 (5, 11) hours after implementation (P = .06). The
      proportion of infants receiving exclusive MBM at 28 days and at discharge was 64%
      and 74%, respectively (P = .40), and the proportion of infants receiving
      exclusive MBM at discharge increased from 37% to 59% (P = .046). In conclusion, a
      multidisciplinary initiative aimed at improving the rate of early milk expression
      was associated with more VLBW infants receiving exclusive MBM at discharge. 

PMID- 25063573
TI  - Predictors of low milk volume among mothers who delivered preterm.
AB  - BACKGROUND: Factors associated with successful provision of mother's own milk
      (MOM) for premature infants in a Japanese neonatal intensive care unit (NICU)
      context are not well known. OBJECTIVE: We determined the independent risk factors
      for low milk volume at day 4 postpartum and formula feeding at the time of NICU
      discharge. METHODS: We reviewed the medical records of mothers who delivered at <
      32 weeks' gestation. We determined maternal, premature infant, and milk
      expression variables predictive of (1) day 4 postpartum milk volume being less
      than the cohort median and (2) formula feeding at the time of NICU discharge,
      reported as adjusted odds ratios (95% confidence interval). RESULTS: Among 85
      dyads, median (quartile range) milk volume on day 4 postpartum was 153 (34-255)
      mL. The rate of formula feeding at discharge was 42%. Mothers delivering by
      cesarean (vs vaginal) delivery had 4.3-fold (1.5-12.4) greater odds of day 4 milk
      volume < median (P < .01). Pregnancy-induced hypertension, delayed milk
      expression initiation, and low pumping frequency were strongly associated with
      cesarean delivery. Subsequently, mothers with day 4 milk volume < median (vs >=
      median) had 7.1-fold (2.6-19.5) greater odds of formula feeding at discharge (P <
      .01). CONCLUSION: Cesarean delivery is associated with lower milk volume on day 4
      but may represent a composite of underlying risk factors for low milk volume in
      the early postpartum period. Further, low milk volume on day 4 is a strong
      correlate of lack of exclusive breast milk feeding at NICU discharge.

PMID- 25063575
TI  - What role for MRI in hamstring strains?   An argument for a difference between  
      recreational and professional athletes.

PMID- 25063574
TI  - Implications of ventricular arrhythmia "bursts" with normal epicardial flow,
      myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial
      infarction reperfusion: a biosignature of direct myocellular injury "downstream
      of downstream".
AB  - AIMS: Establishing epicardial flow with percutaneous coronary intervention (PCI)
      for ST-segment elevation myocardial infarction (STEMI) is necessary but not
      sufficient to ensure nutritive myocardial reperfusion. We evaluated whether
      adding myocardial blush grade (MBG) and quantitative reperfusion ventricular
      arrhythmia "bursts" (VABs) surrogates provide a more informative biosignature of
      optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI)
      3 flow and ST-segment recovery (STR). METHODS AND RESULTS: Anterior STEMI
      patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous
      MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5-14
      SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from
      >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and
      clinical outcomes were examined in patients stratified by MBG and VABs. VABs
      occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in
      75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed
      in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3
      flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median:
      23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a
      factor significantly associated with larger IS (p=0.015). CONCLUSIONS: Despite
      restoration of normal epicardial flow, open microcirculation, and STR,
      concomitant VABs are associated with larger myocardial IS, possibly reflecting
      myocellular injury in reperfusion settings. Combining angiographic and ECG
      parameters of epicardial, microvascular, and cellular response to STEMI
      intervention provides a more predictive "biosignature" of optimal reperfusion
      than do single surrogate markers.

PMID- 25063576
TI  - Development of ARMS-PCR assay for genotyping of Pro12Ala SNP of PPARG gene: a
      cost effective way for case-control studies of type 2 diabetes in developing
      countries.
AB  - Type 2 diabetes (T2D) is a prevalent metabolic disorder across the globe.
      Research is underway on various aspects including genetics to understand and
      control the global epidemic of diabetes. Recently, several SNPs in various genes
      have been associated with T2D. These association studies are mainly carried out
      in the developed countries through Genome Wide Association Scans, with follow-up
      replication/validation studies by high-throughput genotyping techniques (e.g.
      Taqman Technology). Although, similar studies could be conducted in developing
      countries, however, the limiting factors are the associated cost and expertise.
      These factors hamper research into the genetic association and replication
      studies from low-income countries to figure out the role of putatively associated
      SNPs in diabetes. Although, there are several SNP detection methods (e.g. Taqman
      assay, Dot-blot, PCR-RFLP, DGGE, SSCP) but these are either expensive or labor
      intensive or less sensitive. Hence, our aim was to develop a low-cost method for
      the validation of PPARG (Pro12Ala, CCA>GCA) SNP (rs1801282) for its association
      with T2D. Here, we developed a cost-effective and rapid amplification refractory
      mutation specific-PCR (ARMS-PCR) method for this SNP detection. We successfully
      genotyped PPARG SNPs (Pro12Ala) in human samples and the validity of this method
      was confirmed by DNA sequencing of a few representative samples for the three
      different genotypes. Furthermore, ARMS-PCR was applied to T2D patients and
      control samples for the screening of this SNP. 

PMID- 25063577
TI  - Analyzing time-series microarray data reveals key genes in spinal cord injury.
AB  - Although many scholars have utilized high-throughput microarrays to delineate
      gene expression patterns after spinal cord injury (SCI), no study has evaluated
      gene changes in raphe magnus (RM) and somatomotor cortex (SMTC), two areas in
      brain primarily affected by SCI. In present study, we aimed to analyze the
      differentially expressed genes (DEGs) of RM and SMTC between SCI model and sham
      injured control at 4, 24 h, 7, 14, 28 days, and 3 months using microarray dataset
      GSE2270 downloaded from gene expression omnibus and unpaired significance
      analysis of microarray method. Protein-protein interaction (PPI) network was
      constructed for DEGs at crucial time points and significant biological functions
      were enriched using DAVID. The results indicated that more DEGs were identified
      at 14 days in RM and at 4 h/3 months in SMTC after SCI. In the PPI network for
      DEGs at 14 days in RM, interleukin 6, glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), FBJ murine osteosarcoma viral oncogene homolog (FOS), tumor necrosis
      factor, and nuclear receptor subfamily 3, group C, member 1 (glucocorticoid
      receptor) were the top 5 hub genes; In the PPI network for DEGs at 3 months in
      SMTC, the top 5 hub genes were ubiquitin B, Ras-related C3 botulinum toxin
      substrate 1 (rho family, small GTP binding protein Rac1), FOS, Janus kinase 2 and
      vascular endothelial growth factor A. Hedgehog and Wnt signaling pathways were
      the top 2 significant pathways in RM. These hub DEGs and pathways may be
      underlying therapeutic targets for SCI.

PMID- 25063578
TI  - TRS-based PCR as a potential tool for inter-serovar discrimination of Salmonella
      Enteritidis, S. Typhimurium, S. Infantis, S. Virchow, S. Hadar, S. Newport and S.
      Anatum.
AB  - Salmonella enterica subsp. enterica comprises a number of serovars, many of which
      pose an epidemiological threat to humans and are a worldwide cause of morbidity
      and mortality. Most reported food infection outbreaks involve the serovars
      Salmonella Enteritidis and Salmonella Typhimurium. Rapid identification to
      determine the primary sources of the bacterial contamination is important to the
      improvement of public health. In recent years, many DNA-based techniques have
      been applied to genotype Salmonella. Herein, we report the use of a manual TRS
      PCR approach for the differentiation of the Salmonella enterica subspecies
      enterica serovars in a single-tube assay. One hundred seventy Salmonella strains
      were examined in this work. These consisted of serovars S. Enteritidis, S.
      Typhimurium, S. Infantis, S. Virchow, S. Hadar, S. Newport and S. Anatum. Five of
      the TRS-primers, N6(GTG)4, N6(CAC)4, N6(CGG)4, N6(CCG)4 and N6(CTG)4, perfectly
      distinguished the S. Enteritidis and S. Typhimurium serovars, and the N6(GTG)4
      primer additionally grouped the other five frequently isolated serovars. In our
      opinion, the TRS-PCR methodology could be recommended for a quick and simple DNA
      based test for inter-serovar discrimination of Salmonella strains. 

PMID- 25063579
TI  - Association between vacA genotypes and the risk of duodenal ulcer: a meta
      analysis.
AB  - Epidemiological studies have reported the relationship between vacuolating
      cytotoxin A (vacA) s-/m- region genotypes and duodenal ulcer (DU), but the
      results remained inconclusive. We performed the present meta-analysis to
      investigate a more authentic association between vacA s-/m- region genotypes and
      DU. Literature search was performed by searching Embase, PubMed and ISI Web of
      Science databases as well as checking references from identified articles,
      reviews and the abstracts presented at related scientific societies meetings. The
      association was assessed by combined odds ratio (OR) with 95% confidence interval
      (CI). A total of 42 studies were included in our final meta-analysis. The
      combined ORs (95% CIs) showed that vacA s1 (OR = 2.96, 95% CI = 2.34-3.75), m1
      (OR = 1.46, 95% CI = 1.05-2.04) and s1m1 (OR = 1.89, 95% CI = 1.47-2.42) were
      associated with increased DU risk significantly in the overall studied
      population. Subgroup analyses by ethnicity showed that vacA s1 increased the risk
      of DU in Asian countries (OR = 1.92, 95% CI = 1.30-2.83), European countries (OR
      = 3.58, 95% CI = 2.13-6.03) and Latin American countries (OR = 4.20, 95% CI =
      2.21-7.98); vacA m1 increased the risk of DU in Latin American countries (OR =
      2.98, 95% CI = 1.59-5.56); vacA s1m1 increased the risk of DU in Asian countries
      (OR = 2.04, 95% CI = 1.12-3.73) and Latin American countries (OR = 2.05, 95% CI =
      1.20-3.48); vacA s2m1 increased the risk of DU in Latin American countries (OR =
      2.30, 95% CI = 1.17-4.50). The data suggest that genotype testing of vacA s- and
      m- region will be useful in screening susceptible individuals for DU development.

PMID- 25063580
TI  - Aragonite shells are more ancient than calcite ones in bivalves: new evidence
      based on omics.
AB  - Two calcium carbonate crystal polymorphs, aragonite and calcite, are the main
      inorganic components of mollusk shells. Some fossil evidences suggest that
      aragonite shell is more ancient than calcite shell for the Bivalvia. But, the
      molecular biology evidence for the above deduction is absent. In this study, we
      searched for homologs of bivalve aragonite-related and calcite-related shell
      proteins in the oyster genome, and found that no homologs of calcite-related
      shell protein but some homologs of aragonite-related shell proteins in the oyster
      genome. We explained the results as the new evidence to support that aragonite
      shells are more ancient than calcite shells in bivalves combined the published
      biogeological and seawater chemistry data. 

PMID- 25063581
TI  - Enhancing ketamine translational pharmacology via receptor occupancy
      normalization.
AB  - Ketamine is used preclinically and clinically to study schizophrenia and
      depression. Accordingly, it is imperative to understand the temporal relationship
      between the central concentrations and N-methyl-d-aspartate receptor (NMDAR)
      interactions of both ketamine and norketamine, its primary active metabolite,
      across species to assess the translatability of animal models to humans and the
      back-translation of clinical observations to the preclinical realm. However, such
      an interspecies normalization of ketamine and norketamine exposures at different
      clinical and preclinical doses (and their different routes and regimens) is
      lacking. This work defines the NMDAR occupancy (RO) time course following single
      doses of ketamine in rats, nonhuman primates (nhp) and humans to allow direct
      interspecies comparisons of specific ketamine-mediated pharmacodynamics via RO
      normalization. Total plasma concentration (Cp)-time profiles of ketamine and
      norketamine were generated from rats and nhp following a single, memory-impairing
      dose of ketamine; neuropharmacokinetics were determined in rats. [(3)H]MK-801
      displacement studies in rats determined estimated mean (95% confidence interval)
      unbound plasma concentrations (Cp,u) for ketamine and norketamine producing 50%
      RO (IC50) of 1420 (990, 2140) nM and 9110 (5870, 13700) nM, respectively.
      Together, these datasets transformed Cp,u-time data to predicted RO (ROpred)-time
      profiles for rats, nhp and humans at behaviorally relevant ketamine doses.
      Subsequently, this approach helped determine an infusion paradigm in rats
      producing a ROpred-time profile mirroring that for a clinically antidepressant
      infusion. The described indication-independent methodology allows normalization
      to RO at any time following any ketamine dose (regardless of route or regimen) in
      any species by simply quantifying the Cp of ketamine and norketamine. Matching
      temporal RO relationships in animals and humans should allow direct comparisons
      of specific ketamine-dependent NMDAR-based pharmacodynamics. 

PMID- 25063582
TI  - Levels of the Rab GDP dissociation inhibitor (GDI) are altered in the prenatal
      restrain stress mouse model of schizophrenia and are differentially regulated by
      the mGlu2/3 receptor agonists, LY379268 and LY354740.
AB  - LY379268 and LY354740, two agonists of mGlu2/3 metabotropic glutamate receptors,
      display different potencies in mouse models of schizophrenia. This differential
      effect of the two drugs remains unexplained. We performed a proteomic analysis in
      cultured cortical neurons challenged with either LY379268 or LY354740. Among the
      few proteins that were differentially influenced by the two drugs, Rab GDP
      dissociation inhibitor-beta (Rab GDIbeta) was down-regulated by LY379268 and
      showed a trend to an up-regulation in response to LY354740. In cultured
      hippocampal neurons, LY379268 selectively down-regulated the alpha isoform of Rab
      GDI. Rab GDI inhibits the activity of the synaptic vesicle-associated protein,
      Rab3A, and is reduced in the brain of schizophrenic patients. We examined the
      expression of Rab GDI in mice exposed to prenatal stress ("PRS mice"), which have
      been described as a putative model of schizophrenia. Rab GDIalpha protein levels
      were increased in the hippocampus of PRS mice at postnatal days (PND)1 and 21,
      but not at PND60. At PND21, PRS mice also showed a reduced depolarization-evoked
      [(3)H]d-aspartate release in hippocampal synaptosomes. The increase in Rab
      GDIalpha levels in the hippocampus of PRS mice was reversed by a 7-days treatment
      with LY379268 (1 or 10 mg/kg, i.p.), but not by treatment with equal doses of
      LY354740. These data strengthen the validity of PRS mice as a model of
      schizophrenia, and show for the first time a pharmacodynamic difference between
      LY379268 and LY354740 which might be taken into account in an attempt to explain
      the differential effect of the two drugs across mouse models. 

PMID- 25063583
TI  - Treatment Approaches to Congestion Relief in Acute Decompensated HF: Insights
      After DOSE-AHF and CARRESS-HF.
AB  - OPINION STATEMENT: Most patients admitted to the hospital with ADHF do not
      achieve adequate relief of signs and symptoms of congestion. Patients with
      inadequate decongestion are known to be at higher risk of readmission for heart
      failure and mortality, although it is uncertain whether this is a cause or simply
      a marker of increased risk. Nonetheless, adequate decongestion is critical for
      improving quality of life. Based on the DOSE-AHF and CARRESS-HF studies, a high
      dose diuretic regimen consisting of 2.5 times the daily dose of loop diuretic in
      furosemide equivalents, administered in twice-daily bolus doses, is reasonable to
      achieve a goal of 3-5 liters of urine output per day. Transient increases in
      creatinine in the first 4-5 days of diuresis should not be a limiting factor, but
      a prolonged progressive increase in creatinine signals a high-risk patient.
      Current goals for decongestion should be resolution of orthopnea, jugular venous
      pressure of < 8 cm of water, and trace to no peripheral edema. The hope is that
      better measures of assessing complete decongestion will reduce the progression to
      heart failure and mortality. While the best noninvasive method to assess speed of
      congestion has not been determined, it is clear that hemoconcentration (an
      increase in hematocrit) reflects a decrease in plasma volume and decongestion. In
      line monitoring of hemoconcentration may improve the results of ultrafiltration
      therapy by preventing too large and/or too rapid a fall in intravascular volume
      and consequent triggering of neurohormonal activation. Several additional
      strategies such as serelaxin, high-dose mineralocorticoid receptor antagonists,
      and new forms and combinations of natriuretic peptides have shown promising
      results in the relief of congestion in patients with ADHF.

PMID- 25063584
TI  - Female gender doubles executive dysfunction risk in ALS: a case-control study in
      165 patients.
AB  - BACKGROUND: Cognitive impairment, mainly characterised by executive dysfunction,
      occurs in about half of cases in amyotrophic lateral sclerosis (ALS). There is
      evidence that gender influences some clinical features of the disease, but its
      influence on the cognitive spectrum is unknown. Our objective was to investigate
      the impact of gender on cognitive profiles of patients with ALS. METHODS: A
      retrospective study based on an exhaustive neuropsychological battery was
      performed in a group of 165 (70 females, 95 males) sporadic, non-demented
      patients with ALS compared with 134 healthy control participants. This assessment
      primarily focused on executive, memory and language functions. RESULTS: 47 (29%)
      patients revealed impairment in executive function and 30 (18%) patients revealed
      cognitive non-executive impairment. Independent from mood tone and clinical
      variables, a significantly greater executive impairment was determined in female
      patients than in male patients and control participants. The relative risk for
      ALS females having impairment in executive function compared with male patients
      was 2.6 (95% CI 1.6 to 4.4; p=0.0003). ALS females scored lower in Phonemic
      Fluency, Trial Making, and Wisconsin Card Sorting test. CONCLUSIONS: Results
      highlight a significant vulnerability of ALS female patients to develop cognitive
      dysfunctions peculiar to the disease, independently of bulbar onset. The
      explicative hypotheses of the data are focused on two interpretative lines not
      mutually exclusive: the role of gonadal hormones and gender-related brain
      asymmetry pre-existing to the disease. These findings, never reported before in
      the literature, can have important implications for models of ALS pathogenesis
      and for future clinical trial designs.

PMID- 25063586
TI  - Unbiased proteomic and transcript analyses reveal that stathmin-1 silencing
      inhibits colorectal cancer metastasis and sensitizes to 5-fluorouracil treatment.
AB  - Colorectal cancer metastasis is a major cause of mortality worldwide, which may
      only be controlled with novel methods limiting tumor dissemination and
      chemoresistance. High stathmin-1 (STMN1) expression was previously established as
      a hallmark of colorectal cancer progression and predictor of poor survival;
      however, the mechanism of action is less clear. This work demonstrates that STMN1
      silencing arrests tumor-disseminative cascades by inhibiting multiple metastatic
      drivers, and repressing oncogenic and mesenchymal transcription. Using a
      sensitive iTRAQ labeling proteomic approach that quantified differential
      abundance of 4562 proteins, targeting STMN1 expression was shown to reinstate the
      default cellular program of metastatic inhibition, and promote cellular adhesion
      via amplification of hemidesmosomal junctions and intermediate filament
      tethering. Silencing STMN1 also significantly improved chemoresponse to the
      classical colorectal cancer therapeutic agent, 5FU, via a novel caspase-6 (CASP6)
      dependent mechanism. Interestingly, the prometastatic function of STMN1 was
      independent of p53 but required phosphorylations at S25 or S38; abrogating
      phosphorylative events may constitute an alternative route to achieving
      metastatic inhibition. These findings establish STMN1 as a potential target in
      antimetastatic therapy, and demonstrate the power of an approach coupling
      proteomics and transcript analyses in the global assessment of treatment benefits
      and potential side-effects. IMPLICATIONS: Stathmin-1 is a potential candidate in
      colorectal cancer therapy that targets simultaneously the twin problems of
      metastatic spread and chemoresistance.

PMID- 25063588
TI  - Use of herbal medicines by elderly patients: A systematic review.
AB  - OBJECTIVES: We aimed to survey the published literature for articles that
      describe the use of herbal supplements by elderly patients and to summarize
      important aspects of selected studies, including most commonly used supplements,
      study type, study location, and potential hazards of herbal supplement use.
      METHODS: Literature searches were conducted on three scientific/medical
      databases: Medline, Web of Science, and Scopus. Search results were examined for
      articles involving the use of herbal products in the elderly population that met
      selection criteria. RESULTS: Initial searches yielded 1297 articles. Of these
      original results, only 16 met specific selection criteria. Twelve (75%) of
      studies identified were performed in North America. Nine studies (56.25%) were
      conducted in the United States. Seven of the studies were cross-sectional
      (43.8%). The most commonly reported were gingko biloba, garlic, ginseng, aloe
      vera, chamomile, spearmint, and ginger. Of these, gingko and garlic are the most
      commonly used among community-dwelling elderly. Both of these supplements have
      the potential to interact with anticoagulants and produce bruising or bleeding
      problems. CONCLUSIONS: The use of herbal supplements is common among the elderly,
      a population that takes a disproportionate share of prescription medications
      compared to that taken by younger populations. Among the problems uncovered by
      these studies was a lack of dialog between medical professionals and patients
      about the use of herbal supplements. Prescribers need to consider the use of
      herbal supplements and discuss the matter with their elderly patients when making
      decisions about pharmacological treatments.

PMID- 25063589
TI  - The development of a brief jail-based cervical health promotion intervention.
AB  - The primary objective of this article was to describe the development and pilot
      implementation of a brief jail-based cervical health promotion intervention. The
      intervention was guided by a preliminary study of incarcerated women's cervical
      health knowledge, awareness, and health literacy, as well as a social and
      feminist approach to intervention development. We developed and conducted a pilot
      implementation of the Sexual Health Empowerment Project to increase cervical
      health knowledge, reduce barriers related to beliefs about cervical cancer, and
      improve self-efficacy and confidence in navigating health systems. This article
      offers a framework for how empirically and theory-based interventions are
      developed and tailored for a jail setting. Future work should include the
      evaluation of the long-term effects of such a disease-specific program on health
      behaviors and outcomes among high-risk and vulnerable groups of women as they
      leave jails and enter communities. 

PMID- 25063587
TI  - Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a
      major driver of chemically induced skin cancer.
AB  - Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2
      (PTGS2/COX-2) plays a critical role in DMBA/TPA-induced skin tumor induction.
      Although many cell types in the tumor microenvironment express COX-2, the cell
      types in which COX-2 expression is required for tumor promotion are not clearly
      established. Here, cell type-specific Cox-2 gene deletion reveals a vital role
      for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In
      contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis.
      The infrequent, small tumors that develop on mice with an epithelial cell
      specific Cox-2 gene deletion have decreased proliferation and increased cell
      differentiation properties. Blood vessel density is reduced in tumors with an
      epithelial cell-specific Cox-2 gene deletion, compared with littermate control
      tumors, suggesting a reciprocal relationship in tumor progression between COX-2
      expressing tumor epithelial cells and microenvironment endothelial cells.
      Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that
      the prostaglandins PGE2 and PGF2alpha are likely candidates for the epithelial
      cell COX-2-dependent eicosanoids that mediate tumor progression. This study both
      illustrates the value of cell type-specific gene deletions in understanding the
      cellular roles of signal-generating pathways in complex microenvironments and
      emphasizes the benefit of a systems-based lipidomic analysis approach to identify
      candidate lipid mediators of biologic responses. IMPLICATIONS: Cox-2 gene
      deletion demonstrates that intrinsic COX-2 expression in initiated keratinocytes
      is a principal driver of skin carcinogenesis; lipidomic analysis identifies
      likely prostanoid effectors.

PMID- 25063590
TI  - Community health workers as an integral strategy in the REACH U.S. program to
      eliminate health inequities.
AB  - Mounting evidence indicates that community health workers (CHWs) contribute to
      improved behavioral and health outcomes and reductions in health disparities. We
      provide an overview (based on grantee reports and community action plans) that
      describe CHW contributions to 22 Racial and Ethnic Approaches to Community Health
      (REACH) programs funded by the Centers for Disease Control and Prevention from
      2007 to 2012, offering additional evidence of their contributions to the
      effectiveness of community public health programs. We then highlight how CHWs
      helped deliver REACH U.S. community interventions to meet differing needs across
      communities to bridge the gap between health care services and community members,
      build community and individual capacity to plan and implement interventions
      addressing multiple chronic health conditions, and meet community needs in a
      culturally appropriate manner. The experience, skills, and success gained by CHWs
      participating in the REACH U.S. program have fostered important individual
      community-level changes geared to increase health equity. Finally, we underscore
      the importance of CHWs being embedded within these communities and the
      flexibility they offer to intervention strategies, both of which are
      characteristics critical to meeting needs of communities experiencing health
      disparities. CHWs served a vital role in facilitating and leading changes and
      will continue to do so. 

PMID- 25063591
TI  - AUA/SUFU adult urodynamics guideline: a clinical review.
AB  - The American Urological Association/Society of Urodynamics Female Pelvic Medicine
      and Urogenital Reconstruction Adult Urodynamics Guideline was published with the
      intent of guiding the clinician in the role of urodynamics in the evaluation and
      management of complex lower urinary tract conditions. This article examines each
      guideline statement and attempts to provide clinical context for each statement.
      Key points are emphasized in the form of clinical case scenarios, which
      demonstrate application of the principles stressed in this guideline. It is hoped
      the reader will have a better clinical frame of reference relative to each
      statement in these guidelines. 

PMID- 25063592
TI  - Good urodynamic practice: keys to performing a quality UDS study.
AB  - Urodynamics (UDS) is the dynamic study of the storage and voiding function of the
      urinary tract. The goal of the UDS study is to identify the cause of a patient's
      voiding symptoms, assess prognosis or the results of prior therapy, or direct
      management by collecting quantitative measurements while reproducing the
      patient's voiding symptoms where appropriate and possible. Several parts of the
      UDS study are customized for each individual to maximize the utility of the test.
      This article summarizes the key points to performing a quality UDS study that can
      evaluate and diagnose disorders of the lower urinary tract. 

PMID- 25063593
TI  - Can intrinsic sphincter deficiency be diagnosed by urodynamics?
AB  - Intrinsic sphincter deficiency (ISD) is a pathologic condition that is diagnosed
      by using urodynamics to measure Valsalva leak point pressure and maximal urethral
      closure pressure. The diagnosis can be difficult to reach given natural
      discrepancies in these values in women of different age groups and with varying
      degrees of incontinence. By standardizing urodynamic methodologies and
      interpretations to better diagnosis women with ISD, it may be possible to improve
      preoperative planning and outcomes for these patients treated surgically with
      synthetic midurethral slings. 

PMID- 25063594
TI  - Videourodynamics: indications and technique.
AB  - Videourodynamics combines fluoroscopic voiding cystourethrography with
      multichannel urodynamics to better evaluate lower urinary tract symptoms. This
      article reviews current literature and guidelines outlining the indications for
      obtaining this specialized study as well as technique. Appropriate and judicious
      use of fluoro-urodynamics lends to improved diagnostic acumen in a well-selected
      patient population; however, clinicians must be mindful of the added cost, safety
      concerns, and limitations of its use. 

PMID- 25063595
TI  - Urodynamics in stress incontinence: when are they necessary and how do we use
      them?
AB  - Stress urinary incontinence is a prevalent condition that significantly impairs
      the quality of life. This article presents a critical summary of the current
      literature on the use and value of urodynamic studies in the evaluation of stress
      urinary incontinence in women. 

PMID- 25063596
TI  - Urodynamics in male LUTS: when are they necessary and how do we use them?
AB  - In this article, the value of urodynamic studies in the evaluation of treatment
      of male lower urinary tract symptoms is appraised based on current evidence. The
      information gained by urodynamics can be a valuable tool for counseling patients
      considering invasive outlet reduction procedures. 

PMID- 25063597
TI  - Urodynamics in pelvic organ prolapse: when are they helpful and how do we use
      them?
AB  - The routine use of preoperative urodynamics in the woman considering surgery for
      pelvic organ prolapse is a topic of much debate. This article addresses the use
      of urodynamics in patients with pelvic organ prolapse. It specifically discusses
      the utility of urodynamics in the evaluation stress incontinence on prolapse
      reduction (occult stress urinary incontinence) as well as concomitant storage and
      voiding symptoms in these patients. 

PMID- 25063598
TI  - Urodynamics for postprostatectomy incontinence: when are they helpful and how do
      we use them?
AB  - Urodynamics is indicated for the evaluation of postprostatectomy incontinence
      unless an artificial urinary sphincter placement is the preferred option, as in
      cases of severe incontinence, prior radiation, or previous male sling or
      artificial urinary sphincter placement--when male sling is unlikely to achieve
      efficacy. Urodynamics should be performed only when there is a question it can
      answer that would affect treatment choice or outcome. Urodynamic findings of
      detrusor underactivity, overactivity, and reduced compliance are important
      considerations in deciding how best to treat postprostatectomy incontinence.

PMID- 25063599
TI  - Urodynamics in the evaluation of female LUTS: when are they helpful and how do we
      use them?
AB  - Urodynamics remains the test of choice to evaluate lower urinary tract symptoms
      in men and women. Best practices recommend that urodynamics be applied to answer
      a specific urodynamic question. Recent level 1 evidence shows that urodynamics is
      not necessary for the evaluation of pure clinical stress urinary incontinence.
      Urodynamics is also not needed before conservative treatment of overactive
      bladder. Urodynamics still has an important role in the evaluation of mixed
      urinary incontinence and voiding lower urinary tract symptoms. The information
      obtained assists the clinician in confirmation of the diagnosis, counseling the
      patient, and choosing treatment. 

PMID- 25063600
TI  - Urodynamics in the evaluation of the patient with multiple sclerosis: when are
      they helpful and how do we use them?
AB  - Multiple sclerosis (MS) is an autoimmune inflammatory disease that results in
      damage to the myelin sheaths of the nerves in the central nervous system. Urinary
      urgency, frequency, and urgency incontinence are the most common symptoms,
      occurring in 37% to 99% of patients. Voiding symptoms (hesitancy, feeling of
      incomplete bladder emptying, and occasionally urinary retention) are also common
      in this population, occurring in 34% to 79% of patients. Traditionally, filling
      cystometry combined with pressure/flow studies has been a cornerstone of the
      initial evaluation of all patients with neurogenic lower urinary tract
      dysfunction, although recently that practice has been challenged. 

PMID- 25063601
TI  - Neurogenic lower urinary tract dysfunction: how, when, and with which patients do
      we use urodynamics?
AB  - Neurogenic lower urinary tract dysfunction (NLUTD) affects many patients and
      requires close monitoring. Initial studies establishing patients at risk for
      upper tract disease revealed that high detrusor leak point pressures were
      predictive of upper tract disease. Urodynamics in patients with NLUTD have
      specific challenges. Initial studies in patients after an acute injury should be
      delayed until after the spinal shock phase. In children with spinal dysraphism,
      studies should be done early to established potential risk. The goals are
      maintaining low bladder pressures, decreasing risk of infection, and maintaining
      continence. 

PMID- 25063602
TI  - Pressure flow studies in men and women.
AB  - There are well established pressure flow criteria and nomograms for urinary
      obstruction in men. The pressure flow criteria for female urinary obstruction are
      not well established due to differences in female voiding dynamics as compared to
      men. Typically, other information such as radiographic data and clinical symptoms
      are needed to facilitate the diagnosis. Detrusor underactivity remains a poorly
      studied clinical condition without definitive urodynamic diagnostic criteria.
      Modalities proposed for objective analysis of detrusor function such as power
      (watt) factor, linear passive urethral resistance relation and BCI nomogram were
      all developed to analyze male voiding dysfunction. Overall, further investigation
      is needed to establish acceptable urodynamic criteria for defining detrusor
      underactivity in women. 

PMID- 25063603
TI  - Urodynamics.

PMID- 25063604
TI  - Urodynamics.

PMID- 25063648
TI  - Elucidating risk factors for androgen deficiency associated with daily opioid
      use.
AB  - BACKGROUND: Opioids can suppress testosterone in men, which can lead to extensive
      morbidity. Identifying risk factors for androgen deficiency in men using daily
      opioids could improve monitoring and safety. METHODS: In a retrospective cohort
      study, we used Kaiser Permanente Northern California databases to identify men on
      stable doses of opioids. These subjects had no diagnoses of cancer or endocrine
      disorders except treated primary hypothyroidism. Subjects were divided into those
      using long-acting opioids and short-acting opioids. Total testosterone was
      measured in blood drawn in the morning while the subjects were on their regular
      dose of opioid. The association between opioid duration of action and androgen
      deficiency, controlling for dose, body mass index, age, diabetes, hyperlipidemia,
      and hypertension, was assessed using logistic regression. RESULTS: The study
      included 1585 men. Men on long-acting opioids were more likely to be androgen
      deficient than men on short-acting opioids (57% vs 35%, P < 0.001; odds ratio
      [OR] 3.39; 95% confidence interval [CI], 2.39-4.77). As dose increased, the odds
      of androgen deficiency increased; however, dose was more strongly associated with
      androgen deficiency in men on short-acting opioids (OR 1.16; 95% CI, 1.09-1.23,
      for each 10-mg increase in dose) than in men on long-acting opioids (OR 1.01; 95%
      CI, 1.01-1.02). CONCLUSION: Use of long-acting opioids is a key risk factor in
      the development of androgen deficiency. Dose was significantly associated with
      androgen deficiency, but more so for men on short-acting than on long-acting
      opioids.

PMID- 25063649
TI  - The costs of training internal medicine residents in the United States.

PMID- 25063651
TI  - "Candidatus Liberibacter asiaticus" prophage late genes may limit host range and
      culturability.
AB  - "Candidatus Liberibacter asiaticus" is an uncultured alphaproteobacterium that
      systemically colonizes its insect host both inter- and intracellularly and also
      causes a severe, crop-destroying disease of citrus called huanglongbing, or
      citrus "greening." In planta, "Ca. Liberibacter asiaticus" is also systemic but
      phloem limited. "Ca. Liberibacter asiaticus" strain UF506 carries two predicted
      prophages, SC1 and SC2. Bacteriophage particles have been observed in
      experimentally "Ca. Liberibacter asiaticus"-infected periwinkle but not in any
      other host. Comparative gene expression analysis of predicted SC1 late genes
      showed a much higher level of late gene expression, including holin transcripts
      (SC1_gp110), in "Ca. Liberibacter asiaticus"-infected periwinkle relative to "Ca.
      Liberibacter asiaticus"-infected citrus. To functionally characterize predicted
      holin and endolysin activity, SC1_gp110 and two predicted endolysins, one within
      SC1 (SC1_gp035) and another well outside the predicted prophage region
      (CLIBASIA_04790), were cloned and expressed in Escherichia coli. Both SC1 genes
      inhibited bacterial growth consistent with holin and endolysin function. The
      holin (SC1_gp110) promoter region was fused with a uidA reporter on pUFR071, a
      wide bacterial host range (repW) replicon, and used to transform Liberibacter
      crescens strain BT-1 by electroporation. BT-1 is the only liberibacter strain
      cultured to date and was used as a proxy for "Ca. Liberibacter asiaticus."
      pUFR071 was >95% stable without selection in BT-1 for over 20 generations. The
      reporter construct exhibited strong constitutive glucuronidase (GUS) activity in
      culture-grown BT-1 cells. However, GUS reporter activity in BT-1 was suppressed
      in a dose-dependent manner by crude aqueous extracts from psyllids. Taken
      together with plant expression data, these observations indicate that "Ca.
      Liberibacter asiaticus" prophage activation may limit "Ca. Liberibacter
      asiaticus" host range and culturability.

PMID- 25063650
TI  - Polyamine transporters and polyamines increase furfural tolerance during xylose
      fermentation with ethanologenic Escherichia coli strain LY180.
AB  - Expression of genes encoding polyamine transporters from plasmids and polyamine
      supplements increased furfural tolerance (growth and ethanol production) in
      ethanologenic Escherichia coli LY180 (in AM1 mineral salts medium containing
      xylose). This represents a new approach to increase furfural tolerance and may be
      useful for other organisms. Microarray comparisons of two furfural-resistant
      mutants (EMFR9 and EMFR35) provided initial evidence for the importance of
      polyamine transporters. Each mutant contained a single polyamine transporter gene
      that was upregulated over 100-fold (microarrays) compared to that in the parent
      LY180, as well as a mutation that silenced the expression of yqhD. Based on these
      genetic changes, furfural tolerance was substantially reconstructed in the
      parent, LY180. Deletion of potE in EMFR9 lowered furfural tolerance to that of
      the parent. Deletion of potE and puuP in LY180 also decreased furfural tolerance,
      indicating functional importance of the native genes. Of the 8 polyamine
      transporters (18 genes) cloned and tested, half were beneficial for furfural
      tolerance (PotE, PuuP, PlaP, and PotABCD). Supplementing AM1 mineral salts medium
      with individual polyamines (agmatine, putrescine, and cadaverine) also increased
      furfural tolerance but to a smaller extent. In pH-controlled fermentations,
      polyamine transporter plasmids were shown to promote the metabolism of furfural
      and substantially reduce the time required to complete xylose fermentation. This
      increase in furfural tolerance is proposed to result from polyamine binding to
      negatively charged cellular constituents such as nucleic acids and phospholipids,
      providing protection from damage by furfural. 

PMID- 25063652
TI  - Reduction of Legionella spp. in water and in soil by a citrus plant extract
      vapor.
AB  - Legionnaires' disease is a severe form of pneumonia caused by Legionella spp.,
      organisms often isolated from environmental sources, including soil and water.
      Legionella spp. are capable of replicating intracellularly within free-living
      protozoa, and once this has occurred, Legionella is particularly resistant to
      disinfectants. Citrus essential oil (EO) vapors are effective antimicrobials
      against a range of microorganisms, with reductions of 5 log cells ml(-1) on a
      variety of surfaces. The aim of this investigation was to assess the efficacy of
      a citrus EO vapor against Legionella spp. in water and in soil systems.
      Reductions of viable cells of Legionella pneumophila, Legionella longbeachae,
      Legionella bozemanii, and an intra-amoebal culture of Legionella pneumophila
      (water system only) were assessed in soil and in water after exposure to a citrus
      EO vapor at concentrations ranging from 3.75 mg/liter air to 15g/liter air.
      Antimicrobial efficacy via different delivery systems (passive and active
      sintering of the vapor) was determined in water, and gas chromatography-mass
      spectrometry (GC-MS) analysis of the antimicrobial components (linalool, citral,
      and beta-pinene) was conducted. There was up to a 5-log cells ml(-1) reduction in
      Legionella spp. in soil after exposure to the citrus EO vapors (15 mg/liter air).
      The most susceptible strain in water was L. pneumophila, with a 4-log cells ml(
      1) reduction after 24 h via sintering (15 g/liter air). Sintering the vapor
      through water increased the presence of the antimicrobial components, with a 61%
      increase of linalool. Therefore, the appropriate method of delivery of an
      antimicrobial citrus EO vapor may go some way in controlling Legionella spp. from
      environmental sources. 

PMID- 25063653
TI  - Acetoin synthesis acquisition favors Escherichia coli growth at low pH.
AB  - Some members of the family Enterobacteriaceae ferment sugars via the mixed-acid
      fermentation pathway. This yields large amounts of acids, causing strong and
      sometimes even lethal acidification of the environment. Other family members
      employ the 2,3-butanediol fermentation pathway, which generates comparatively
      less acidic and more neutral end products, such as acetoin and 2,3-butanediol. In
      this work, we equipped Escherichia coli MG1655 with the budAB operon, encoding
      the acetoin pathway, from Serratia plymuthica RVH1 and investigated how this
      affected the ability of E. coli to cope with acid stress during growth. Acetoin
      fermentation prevented lethal medium acidification by E. coli in lysogeny broth
      (LB) supplemented with glucose. It also supported growth and higher stationary
      phase cell densities in acidified LB broth with glucose (pH 4.10 to 4.50) and in
      tomato juice (pH 4.40 to 5.00) and reduced the minimal pH at which growth could
      be initiated. On the other hand, the acetoin-producing strain was outcompeted by
      the nonproducer in a mixed-culture experiment at low pH, suggesting a fitness
      cost associated with acetoin production. Finally, we showed that acetoin
      production profoundly changes the appearance of E. coli on several diagnostic
      culture media. Natural E. coli strains that have laterally acquired budAB genes
      may therefore have escaped detection thus far. This study demonstrates the
      potential importance of acetoin fermentation in the ecology of E. coli in the
      food chain and contributes to a better understanding of the microbiological
      stability and safety of acidic foods. 

PMID- 25063654
TI  - Functional and structural responses of hyporheic biofilms to varying sources of
      dissolved organic matter.
AB  - Headwater streams are tightly connected with the terrestrial milieu from which
      they receive deliveries of organic matter, often through the hyporheic zone, the
      transition between groundwater and streamwater. Dissolved organic matter (DOM)
      from terrestrial sources (that is, allochthonous) enters the hyporheic zone,
      where it may mix with DOM from in situ production (that is, autochthonous) and
      where most of the microbial activity takes place. Allochthonous DOM is typically
      considered resistant to microbial metabolism compared to autochthonous DOM. The
      composition and functioning of microbial biofilm communities in the hyporheic
      zone may therefore be controlled by the relative availability of allochthonous
      and autochthonous DOM, which can have implications for organic matter processing
      in stream ecosystems. Experimenting with hyporheic biofilms exposed to model
      allochthonous and autochthonous DOM and using 454 pyrosequencing of the 16S rRNA
      (targeting the "active" community composition) and of the 16S rRNA gene
      (targeting the "bulk" community composition), we found that allochthonous DOM may
      drive shifts in community composition whereas autochthonous DOM seems to affect
      community composition only transiently. Our results suggest that priority effects
      based on resource-driven stochasticity shape the community composition in the
      hyporheic zone. Furthermore, measurements of extracellular enzymatic activities
      suggest that the additions of allochthonous and autochthonous DOM had no clear
      effect on the function of the hyporheic biofilms, indicative of functional
      redundancy. Our findings unravel possible microbial mechanisms that underlie the
      buffering capacity of the hyporheic zone and that may confer stability to stream
      ecosystems. 

PMID- 25063655
TI  - Galactosyl-lactose sialylation using Trypanosoma cruzi trans-sialidase as the
      biocatalyst and bovine kappa-casein-derived glycomacropeptide as the donor
      substrate.
AB  - trans-Sialidase (TS) enzymes catalyze the transfer of sialyl (Sia) residues from
      Sia(alpha2-3)Gal(beta1-x)-glycans (sialo-glycans) to Gal(beta1-x)-glycans (asialo
      glycans). Aiming to apply this concept for the sialylation of linear and branched
      (Gal)nGlc oligosaccharide mixtures (GOS) using bovine kappa-casein-derived
      glycomacropeptide (GMP) as the sialic acid donor, a kinetic study has been
      carried out with three components of GOS, i.e., 3'-galactosyl-lactose (beta3'
      GL), 4'-galactosyl-lactose (beta4'-GL), and 6'-galactosyl-lactose (beta6'-GL).
      This prebiotic GOS is prepared from lactose by incubation with suitable beta
      galactosidases, whereas GMP is a side-stream product of the dairy industry. The
      trans-sialidase from Trypanosoma cruzi (TcTS) was expressed in Escherichia coli
      and purified. Its temperature and pH optima were determined to be 25 degrees C
      and pH 5.0, respectively. GMP [sialic acid content, 3.6% (wt/wt); N
      acetylneuraminic acid (Neu5Ac), >99%; (alpha2-3)-linked Neu5Ac, 59%] was found to
      be an efficient sialyl donor, and up to 95% of the (alpha2-3)-linked Neu5Ac could
      be transferred to lactose when a 10-fold excess of this acceptor substrate was
      used. The products of the TcTS-catalyzed sialylation of beta3'-GL, beta4'-GL, and
      beta6'-GL, using GMP as the sialic acid donor, were purified, and their
      structures were elucidated by nuclear magnetic resonance spectroscopy.
      Monosialylated beta3'-GL and beta4'-GL contained Neu5Ac connected to the terminal
      Gal residue; however, in the case of beta6'-GL, TcTS was shown to sialylate the 3
      position of both the internal and terminal Gal moieties, yielding two different
      monosialylated products and a disialylated structure. Kinetic analyses showed
      that TcTS had higher affinity for the GL substrates than lactose, while the Vmax
      and kcat values were higher in the case of lactose. 

PMID- 25063656
TI  - Meta-analyses of Dehalococcoides mccartyi strain 195 transcriptomic profiles
      identify a respiration rate-related gene expression transition point and
      interoperon recruitment of a key oxidoreductase subunit.
AB  - A cDNA-microarray was designed and used to monitor the transcriptomic profile of
      Dehalococcoides mccartyi strain 195 (in a mixed community) respiring various
      chlorinated organics, including chloroethenes and 2,3-dichlorophenol. The
      cultures were continuously fed in order to establish steady-state respiration
      rates and substrate levels. The organization of array data into a clustered heat
      map revealed two major experimental partitions. This partitioning in the data set
      was further explored through principal component analysis. The first two
      principal components separated the experiments into those with slow (1.6+/-0.6
      MUM Cl-/h)- and fast (22.9+/-9.6 MUM Cl-/h)-respiring cultures. Additionally, the
      transcripts with the highest loadings in these principal components were
      identified, suggesting that those transcripts were responsible for the
      partitioning of the experiments. By analyzing the transcriptomes (n=53) across
      experiments, relationships among transcripts were identified, and hypotheses
      about the relationships between electron transport chain members were proposed.
      One hypothesis, that the hydrogenases Hup and Hym and the formate dehydrogenase
      like oxidoreductase (DET0186-DET0187) form a complex (as displayed by their tight
      clustering in the heat map analysis), was explored using a nondenaturing protein
      separation technique combined with proteomic sequencing. Although these proteins
      did not migrate as a single complex, DET0112 (an FdhB-like protein encoded in the
      Hup operon) was found to comigrate with DET0187 rather than with the catalytic
      Hup subunit DET0110. On closer inspection of the genome annotations of all
      Dehalococcoides strains, the DET0185-to-DET0187 operon was found to lack a key
      subunit, an FdhB-like protein. Therefore, on the basis of the transcriptomic,
      genomic, and proteomic evidence, the place of the missing subunit in the DET0185
      to-DET0187 operon is likely filled by recruiting a subunit expressed from the Hup
      operon (DET0112).

PMID- 25063657
TI  - Germination of Aspergillus niger conidia is triggered by nitrogen compounds
      related to L-amino acids.
AB  - Conidial germination is fundamentally important to the growth and dissemination
      of most fungi. It has been previously shown (K. Hayer, M. Stratford, and D. B.
      Archer, Appl. Environ. Microbiol. 79:6924-6931, 2013,
      http://dx.doi.org/10.1128/AEM.02061-13), using sugar analogs, that germination is
      a 2-stage process involving triggering of germination and then nutrient uptake
      for hyphal outgrowth. In the present study, we tested this 2-stage germination
      process using a series of nitrogen-containing compounds for the ability to
      trigger the breaking of dormancy of Aspergillus niger conidia and then to support
      the formation of hyphae by acting as nitrogen sources. Triggering and germination
      were also compared between A. niger and Aspergillus nidulans using 2-deoxy-D
      glucose (trigger), D-galactose (nontrigger in A. niger but trigger in A.
      nidulans), and an N source (required in A. niger but not in A. nidulans).
      Although most of the nitrogen compounds studied served as nitrogen sources for
      growth, only some nitrogen compounds could trigger germination of A. niger
      conidia, and all were related to L-amino acids. Using L-amino acid analogs
      without either the amine or the carboxylic acid group revealed that both the
      amine and carboxylic acid groups were essential for an L-amino acid to serve as a
      trigger molecule. Generally, conidia were able to sense and recognize nitrogen
      compounds that fitted into a specific size range. There was no evidence of uptake
      of either triggering or nontriggering compounds over the first 90 min of A. niger
      conidial germination, suggesting that the germination trigger sensors are not
      located within the spore.

PMID- 25063658
TI  - A desaturase gene involved in the formation of 1,14-nonadecadiene in
      Synechococcus sp. strain PCC 7002.
AB  - The marine cyanobacterium Synechococcus sp. strain PCC 7002 synthesizes two
      alkenes, 1-nonadecene and 1,14-nonadecadiene. Whereas the genetic basis for the
      biosynthesis of the terminal double bond in both alkenes has been characterized,
      the origin of the internal double bond in 1,14-nonadecadiene has not. In this
      study, we demonstrate that a gene encoding an uncharacterized desaturase is
      involved in the formation of the internal double bond of 1,14-nonadecadiene.
      Further, at low temperatures, the desaturase gene is essential for growth, and in
      wild-type cells the levels of 1,14-nonadecadiene increase relative to that of
      cells grown at 38 degrees C. These data suggest that 1,14-nonadecadiene plays a
      role in responding to cold stress. 

PMID- 25063659
TI  - Genomic characterization and transcriptional studies of the starch-utilizing
      strain Bifidobacterium adolescentis 22L.
AB  - Bifidobacteria are members of the gut microbiota, but the genetic basis for their
      adaptation to the human gut is poorly understood. The analysis of the 2,203,222
      bp genome of Bifidobacterium adolescentis 22L revealed a nutrient acquisition
      strategy that targets diet/plant-derived glycans, in particular starch and starch
      like carbohydrates. Starch-like carbohydrates were shown to support the growth of
      B. adolescentis 22L. Transcriptome profiling of 22L cultures grown under in vitro
      conditions or during colonization of the murine gut by RNA sequencing and
      quantitative real-time PCR assays revealed the expression of a set of chromosomal
      loci responsible for starch metabolism as well as for pilus production. Such
      extracellular structures include so-called sortase-dependent and type IVb pili,
      which may be involved in gut colonization of 22L through adhesion to
      extracellular matrix proteins. 

PMID- 25063660
TI  - FLP-FRT-based method to obtain unmarked deletions of CHU_3237 (porU) and large
      genomic fragments of Cytophaga hutchinsonii.
AB  - Cytophaga hutchinsonii is a widely distributed cellulolytic bacterium in the
      phylum Bacteroidetes. It can digest crystalline cellulose rapidly without free
      cellulases or cellulosomes. The mechanism of its cellulose utilization remains a
      mystery. We developed an efficient method based on a linear DNA double-crossover
      and FLP-FRT recombination system to obtain unmarked deletions of both single
      genes and large genomic fragments in C. hutchinsonii. Unmarked deletion of
      CHU_3237 (porU), an ortholog of the C-terminal signal peptidase of a type IX
      secretion system (T9SS), resulted in defects in colony spreading, cellulose
      degradation, and protein secretion, indicating that it is a component of the T9SS
      and that T9SS plays an important role in cellulose degradation by C.
      hutchinsonii. Furthermore, deletions of four large genomic fragments were
      obtained using our method, and the sizes of the excised fragments varied from 9
      to 19 kb, spanning from 6 to 22 genes. The customized FLP-FRT method provides an
      efficient tool for more rapid progress in the cellulose degradation mechanism and
      other physiological aspects of C. hutchinsonii. 

PMID- 25063661
TI  - Screening of a Leptospira biflexa mutant library to identify genes involved in
      ethidium bromide tolerance.
AB  - Leptospira spp. are spirochete bacteria comprising both pathogenic and free
      living species. The saprophyte L. biflexa is a model bacterium for studying
      leptospiral biology due to relative ease of culturing and genetic manipulation.
      In this study, we constructed a library of 4,996 random transposon mutants in L.
      biflexa. We screened the library for increased susceptibility to the DNA
      intercalating agent, ethidium bromide (EtBr), in order to identify genetic
      determinants that reduce L. biflexa susceptibility to antimicrobial agents. By
      phenotypic screening, using subinhibitory EtBr concentrations, we identified 29
      genes that, when disrupted via transposon insertion, led to increased sensitivity
      of the bacteria to EtBr. At the functional level, these genes could be
      categorized by function as follows: regulation and signaling (n=11), transport
      (n=6), membrane structure (n=5), stress response (n=2), DNA damage repair (n=1),
      and other processes (n=3), while 1 gene had no predicted function. Genes involved
      in transport (including efflux pumps) and regulation (two-component systems, anti
      sigma factor antagonists, etc.) were overrepresented, demonstrating that these
      genes are major contributors to EtBr tolerance. This finding suggests that
      transport genes which would prevent EtBr to enter the cell cytoplasm are critical
      for EtBr resistance. We identified genes required for the growth of L. biflexa in
      the presence of sublethal EtBr concentration and characterized their potential as
      antibiotic resistance determinants. This study will help to delineate mechanisms
      of adaptation to toxic compounds, as well as potential mechanisms of antibiotic
      resistance development in pathogenic L. interrogans.

PMID- 25063662
TI  - Urea uptake and carbon fixation by marine pelagic bacteria and archaea during the
      Arctic summer and winter seasons.
AB  - How Arctic climate change might translate into alterations of biogeochemical
      cycles of carbon (C) and nitrogen (N) with respect to inorganic and organic N
      utilization is not well understood. This study combined 15N uptake rate
      measurements for ammonium, nitrate, and urea with 15N- and 13C-based DNA stable
      isotope probing (SIP). The objective was to identify active bacterial and archeal
      plankton and their role in N and C uptake during the Arctic summer and winter
      seasons. We hypothesized that bacteria and archaea would successfully compete for
      nitrate and urea during the Arctic winter but not during the summer, when
      phytoplankton dominate the uptake of these nitrogen sources. Samples were
      collected at a coastal station near Barrow, AK, during August and January. During
      both seasons, ammonium uptake rates were greater than those for nitrate or urea,
      and nitrate uptake rates remained lower than those for ammonium or urea. SIP
      experiments indicated a strong seasonal shift of bacterial and archaeal N
      utilization from ammonium during the summer to urea during the winter but did not
      support a similar seasonal pattern of nitrate utilization. Analysis of 16S rRNA
      gene sequences obtained from each SIP fraction implicated marine group I
      Crenarchaeota (MGIC) as well as Betaproteobacteria, Firmicutes, SAR11, and SAR324
      in N uptake from urea during the winter. Similarly, 13C SIP data suggested dark
      carbon fixation for MGIC, as well as for several proteobacterial lineages and the
      Firmicutes. These data are consistent with urea-fueled nitrification by polar
      archaea and bacteria, which may be advantageous under dark conditions.

PMID- 25063664
TI  - Lactobacillus reuteri 100-23 modulates urea hydrolysis in the murine stomach.
AB  - Comparisons of in vivo (mouse stomach) and in vitro (laboratory culture)
      transcriptomes of Lactobacillus reuteri strain 100-23 were made by microarray
      analysis. These comparisons revealed the upregulation of genes associated with
      acid tolerance, including urease production, in the mouse stomach. Inactivation
      of the ureC gene reduced the acid tolerance of strain 100-23 in vitro, and the
      mutant was outcompeted by the wild type in the gut of ex-Lactobacillus-free mice.
      Urine analysis showed that stable isotope-labeled urea, administered by gavage,
      was metabolized to a greater extent in Lactobacillus-free mice than animals
      colonized by strain 100-23. This surprising observation was associated with
      higher levels of urease activity and fecal-type bacteria in the stomach digesta
      of Lactobacillus-free mice. Despite the modulation of urea hydrolysis in the
      stomach, recycling of urea nitrogen in the murine host was not affected since the
      essential amino acid isoleucine, labeled with a stable isotope, was detected in
      the livers of both Lactobacillus-free and 100-23-colonized animals. Therefore,
      our experiments reveal a new and unexpected impact of Lactobacillus colonization
      on urea hydrolysis in the murine gut. 

PMID- 25063663
TI  - Effects of high hydrostatic pressure on coastal bacterial community abundance and
      diversity.
AB  - Hydrostatic pressure is an important parameter influencing the distribution of
      microbial life in the ocean. In this study, the response of marine bacterial
      populations from surface waters to pressures representative of those under deep
      sea conditions was examined. Southern California coastal seawater collected 5 m
      below the sea surface was incubated in microcosms, using a range of temperatures
      (16 to 3 degrees C) and hydrostatic pressure conditions (0.1 to 80 MPa). Cell
      abundance decreased in response to pressure, while diversity increased. The
      morphology of the community also changed with pressurization to a predominant
      morphotype of small cocci. The pressure-induced community changes included an
      increase in the relative abundance of Alphaproteobacteria, Gammaproteobacteria,
      Actinobacteria, and Flavobacteria largely at the expense of
      Epsilonproteobacteria. Culturable high-pressure-surviving bacteria were obtained
      and found to be phylogenetically similar to isolates from cold and/or deep-sea
      environments. These results provide novel insights into the response of surface
      water bacteria to changes in hydrostatic pressure. 

PMID- 25063665
TI  - GH51 arabinofuranosidase and its role in the methylglucuronoarabinoxylan
      utilization system in Paenibacillus sp. strain JDR-2.
AB  - Methylglucuronoarabinoxylan (MeGAXn) from agricultural residues and energy crops
      is a significant yet underutilized biomass resource for production of biofuels
      and chemicals. Mild thermochemical pretreatment of bagasse yields MeGAXn
      requiring saccharifying enzymes for conversion to fermentable sugars. A
      xylanolytic bacterium, Paenibacillus sp. strain JDR-2, produces an extracellular
      cell-associated GH10 endoxylanse (XynA1) which efficiently depolymerizes
      methylglucuronoxylan (MeGXn) from hardwoods coupled with assimilation of
      oligosaccharides for further processing by intracellular GH67 alpha
      glucuronidase, GH10 endoxylanase, and GH43 beta-xylosidase. This process has been
      ascribed to genes that comprise a xylan utilization regulon that encodes XynA1
      and includes a gene cluster encoding transcriptional regulators, ABC
      transporters, and intracellular enzymes that convert assimilated oligosaccharides
      to fermentable sugars. Here we show that Paenibacillus sp. JDR-2 utilized MeGAXn
      without accumulation of oligosaccharides in the medium. The Paenibacillus sp. JDR
      2 growth rate on MeGAXn was 3.1-fold greater than that on oligosaccharides
      generated from MeGAXn by XynA1. Candidate genes encoding GH51
      arabinofuranosidases with potential roles were identified. Following growth on
      MeGAXn, quantitative reverse transcription-PCR identified a cluster of genes
      encoding a GH51 arabinofuranosidase (AbfB) and transcriptional regulators which
      were coordinately expressed along with the genes comprising the xylan utilization
      regulon. The action of XynA1 on MeGAXn generated arabinoxylobiose,
      arabinoxylotriose, xylobiose, xylotriose, and methylglucuronoxylotriose.
      Recombinant AbfB processed arabinoxylooligosaccharides to xylooligosaccharides
      and arabinose. MeGAXn processing by Paenibacillus sp. JDR-2 may be achieved by
      extracellular depolymerization by XynA1 coupled to assimilation of
      oligosaccharides and further processing by intracellular enzymes, including AbfB.
      Paenibacillus sp. JDR-2 provides a GH10/GH67 system complemented with genes
      encoding intracellular GH51 arabinofuranosidases for efficient utilization of
      MeGAXn. 

PMID- 25063667
TI  - Gammaproteobacterial methanotrophs dominate cold methane seeps in floodplains of
      West Siberian rivers.
AB  - A complex system of muddy fluid-discharging and methane (CH4)-releasing seeps was
      discovered in a valley of the river Mukhrinskaya, one of the small rivers of the
      Irtysh Basin, West Siberia. CH4 flux from most (90%) of these gas ebullition
      sites did not exceed 1.45 g CH4 h(-1), while some seeps emitted up to 5.54 g CH4
      h(-1). The delta(13)C value of methane released from these seeps varied between 
      71.1 and -71.30/00, suggesting its biogenic origin. Although the seeps were
      characterized by low in situ temperatures (3.5 to 5 degrees C), relatively high
      rates of methane oxidation (15.5 to 15.9 nmol CH4 ml(-1) day(-1)) were measured
      in mud samples. Fluorescence in situ hybridization detected 10(7) methanotrophic
      bacteria (MB) per g of mud (dry weight), which accounted for up to 20.5% of total
      bacterial cell counts. Most (95.8 to 99.3%) methanotroph cells were type I
      (gammaproteobacterial) MB. The diversity of methanotrophs in this habitat was
      further assessed by pyrosequencing of pmoA genes, encoding particulate methane
      monooxygenase. A total of 53,828 pmoA gene sequences of seep-inhabiting
      methanotrophs were retrieved and analyzed. Nearly all of these sequences
      affiliated with type I MB, including the Methylobacter-Methylovulum-Methylosoma
      group, lake cluster 2, and several as-yet-uncharacterized methanotroph clades.
      Apparently, microbial communities attenuating methane fluxes from these local but
      strong CH4 sources in floodplains of high-latitude rivers have a large proportion
      of potentially novel, psychrotolerant methanotrophs, thereby providing a
      challenge for future isolation studies. 

PMID- 25063669
TI  - Withdrawal of prolonged antidepressant therapy and Takotsubo syndrome.

PMID- 25063668
TI  - Biofilm formation on biotic and abiotic surfaces in the presence of
      antimicrobials by Escherichia coli Isolates from cases of bovine mastitis.
AB  - Escherichia coli is a highly adaptive microorganism, and its ability to form
      biofilms under certain conditions can be critical for antimicrobial resistance.
      The adhesion of four E. coli isolates from bovine mastitis to bovine mammary
      alveolar (MAC-T) cells, biofilm production on a polystyrene surface, and the
      expression profiles of the genes fliC, csgA, fimA, and luxS in the presence of
      enrofloxacin, gentamicin, co-trimoxazole, and ampicillin at half of the MIC were
      investigated. Increased adhesion of E. coli isolates in the presence of
      antimicrobials was not observed; however, increased internalization of some
      isolates was observed by confocal microscopy. All of the antimicrobials induced
      the formation of biofilms by at least one isolate, whereas enrofloxacin and co
      trimoxazole decreased biofilm formation by at least one isolate. Quantitative PCR
      analysis revealed that all four genes were differentially expressed when bacteria
      were exposed to subinhibitory concentrations of antimicrobials, with expression
      altered on the order of 1.5- to 22-fold. However, it was not possible to
      associate gene expression with induction or reduction of biofilm formation in the
      presence of the antimicrobials. Taken together, the results demonstrate that
      antimicrobials could induce biofilm formation by some isolates, in addition to
      inducing MAC-T cell invasion, a situation that might occur in vivo, potentially
      resulting in a bacterial reservoir in the udder, which might explain some cases
      of persistent mastitis in herds. 

PMID- 25063671
TI  - What can we learn from a dying poet?

PMID- 25063672
TI  - The Janus kinase 2 inhibitor fedratinib inhibits thiamine uptake: a putative
      mechanism for the onset of Wernicke's encephalopathy.
AB  - The clinical development of fedratinib, a Janus kinase (JAK2) inhibitor, was
      terminated after reports of Wernicke's encephalopathy in myelofibrosis patients.
      Since Wernicke's encephalopathy is induced by thiamine deficiency, investigations
      were conducted to probe possible mechanisms through which fedratinib may lead to
      a thiamine-deficient state. In vitro studies indicate that fedratinib potently
      inhibits the carrier-mediated uptake and transcellular flux of thiamine in Caco-2
      cells, suggesting that oral absorption of dietary thiamine is significantly
      compromised by fedratinib dosing. Transport studies with recombinant human
      thiamine transporters identified the individual human thiamine transporter
      (hTHTR2) that is inhibited by fedratinib. Inhibition of thiamine uptake appears
      unique to fedratinib and is not shared by marketed JAK inhibitors, and this
      observation is consistent with the known structure-activity relationship for the
      binding of thiamine to its transporters. The results from these studies provide a
      molecular basis for the development of Wernicke's encephalopathy upon fedratinib
      treatment and highlight the need to evaluate interactions of investigational
      drugs with nutrient transporters in addition to classic xenobiotic transporters. 

PMID- 25063666
TI  - Microbial community stratification controlled by the subseafloor fluid flow and
      geothermal gradient at the Iheya North hydrothermal field in the Mid-Okinawa
      Trough (Integrated Ocean Drilling Program Expedition 331).
AB  - The impacts of lithologic structure and geothermal gradient on subseafloor
      microbial communities were investigated at a marginal site of the Iheya North
      hydrothermal field in the Mid-Okinawa Trough. Subsurface marine sediments
      composed of hemipelagic muds and volcaniclastic deposits were recovered through a
      depth of 151 m below the seafloor at site C0017 during Integrated Ocean Drilling
      Program Expedition 331. Microbial communities inferred from 16S rRNA gene clone
      sequencing in low-temperature hemipelagic sediments were mainly composed of
      members of the Chloroflexi and deep-sea archaeal group. In contrast, 16S rRNA
      gene sequences of marine group I Thaumarchaeota dominated the microbial phylotype
      communities in the coarse-grained pumiceous gravels interbedded between the
      hemipelagic sediments. Based on the physical properties of sediments such as
      temperature and permeability, the porewater chemistry, and the microbial
      phylotype compositions, the shift in the physical properties of the sediments is
      suggested to induce a potential subseafloor recharging flow of oxygenated
      seawater in the permeable zone, leading to the generation of variable chemical
      environments and microbial communities in the subseafloor habitats. In addition,
      the deepest section of sediments under high-temperature conditions (~90 degrees
      C) harbored the sequences of an uncultivated archaeal lineage of hot water
      crenarchaeotic group IV that may be associated with the high-temperature
      hydrothermal fluid flow. These results indicate that the subseafloor microbial
      community compositions and functions at the marginal site of the hydrothermal
      field are highly affected by the complex fluid flow structure, such as recharging
      seawater and underlying hydrothermal fluids, coupled with the lithologic
      transition of sediments. 

PMID- 25063673
TI  - Aberrant methylation of tRNAs links cellular stress to neuro-developmental
      disorders.
AB  - Mutations in the cytosine-5 RNA methyltransferase NSun2 cause microcephaly and
      other neurological abnormalities in mice and human. How post-transcriptional
      methylation contributes to the human disease is currently unknown. By comparing
      gene expression data with global cytosine-5 RNA methylomes in patient fibroblasts
      and NSun2-deficient mice, we find that loss of cytosine-5 RNA methylation
      increases the angiogenin-mediated endonucleolytic cleavage of transfer RNAs
      (tRNA) leading to an accumulation of 5' tRNA-derived small RNA fragments.
      Accumulation of 5' tRNA fragments in the absence of NSun2 reduces protein
      translation rates and activates stress pathways leading to reduced cell size and
      increased apoptosis of cortical, hippocampal and striatal neurons.
      Mechanistically, we demonstrate that angiogenin binds with higher affinity to
      tRNAs lacking site-specific NSun2-mediated methylation and that the presence of
      5' tRNA fragments is sufficient and required to trigger cellular stress
      responses. Furthermore, the enhanced sensitivity of NSun2-deficient brains to
      oxidative stress can be rescued through inhibition of angiogenin during
      embryogenesis. In conclusion, failure in NSun2-mediated tRNA methylation
      contributes to human diseases via stress-induced RNA cleavage. 

PMID- 25063674
TI  - A positive signal prevents secretory membrane cargo from recycling between the
      Golgi and the ER.
AB  - The Golgi complex and ER are dynamically connected by anterograde and retrograde
      trafficking pathways. To what extent and by what mechanism outward-bound cargo
      proteins escape retrograde trafficking has been poorly investigated. Here, we
      analysed the behaviour of several membrane proteins at the ER/Golgi interface in
      live cells. When Golgi-to-plasma membrane transport was blocked, vesicular
      stomatitis virus glycoprotein (VSVG), which bears an ER export signal,
      accumulated in the Golgi, whereas an export signal-deleted version of VSVG
      attained a steady state determined by the balance of retrograde and anterograde
      traffic. A similar behaviour was displayed by EGF receptor and by a model tail
      anchored protein, whose retrograde traffic was slowed by addition of VSVG's
      export signal. Retrograde trafficking was energy- and Rab6-dependent, and Rab6
      inhibition accelerated signal-deleted VSVG's transport to the cell surface. Our
      results extend the dynamic bi-directional relationship between the Golgi and ER
      to include surface-directed proteins, uncover an unanticipated role for export
      signals at the Golgi complex, and identify recycling as a novel factor that
      regulates cargo transport out of the early secretory pathway. 

PMID- 25063676
TI  - Stop competing, start talking!

PMID- 25063675
TI  - Reduced pachytene piRNAs and translation underlie spermiogenic arrest in
      Maelstrom mutant mice.
AB  - Pachytene piRNAs are a class of Piwi-interacting small RNAs abundant in
      spermatids of the adult mouse testis. They are processed from piRNA primary
      transcripts by a poorly understood mechanism and, unlike fetal transposon-derived
      piRNAs, lack complementary targets in the spermatid transcriptome. We report that
      immunopurified complexes of a conserved piRNA pathway protein Maelstrom (MAEL)
      are enriched in MIWI (Piwi partner of pachytene piRNAs), Tudor-domain proteins
      and processing intermediates of pachytene piRNA primary transcripts. We provide
      evidence of functional significance of these complexes in Mael129 knockout mice
      that exhibit spermiogenic arrest with acrosome and flagellum malformation.
      Mael129-null mutant testes possess low levels of piRNAs derived from MAEL
      associated piRNA precursors and exhibit reduced translation of numerous
      spermiogenic mRNAs including those encoding acrosome and flagellum proteins.
      These translation defects in haploid round spermatids are likely indirect, as
      neither MAEL nor piRNA precursors associate with polyribosomes, and they may
      arise from an imbalance between pachytene piRNAs and MIWI.

PMID- 25063678
TI  - Human hepatic stellate cells are not permissive for hepatitis C virus entry and
      replication.
AB  - BACKGROUND: Chronic HCV infection is associated with the development of hepatic
      fibrosis. The direct role of HCV in the fibrogenic process is unknown.
      Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is
      debated. OBJECTIVE: To assess whether human HSCs are susceptible to HCV
      infection. DESIGN: We combined a set of original HCV models, including the
      infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing
      the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic
      genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs
      from different patients and the LX-2 cell line, to assess whether HCV can
      infect/replicate in HSCs. RESULTS: In contrast with the hepatocyte cell line Huh
      7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells.
      The cellular expression of host cellular factors required for HCV entry was high
      in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81.
      Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b
      subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which
      expressed low levels of cellular factors known to play a key role in the HCV life
      cycle, suggesting that human HSCs are not permissive for HCV replication.
      CONCLUSIONS: Human HSCs are refractory to HCV infection. Both HCV entry and
      replication are deficient in these cells, regardless of the HCV genotype and
      origin of the cells. Thus, HCV infection of HSCs does not play a role in liver
      fibrosis. These results do not rule out a direct role of HCV infection of
      hepatocytes in the fibrogenic process.

PMID- 25063677
TI  - TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial
      homeostasis.
AB  - Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells
      (IECs) regulates distinct immune responses to microbes; however, the specific
      cellular machinery that controls this mechanism has not been fully identified.
      Here we provide genetic evidences that the recycling endosomal compartment in
      enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting
      mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome
      resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus,
      in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine
      production, inflammatory bowel phenotype, and early mortality. Unlike wild-type
      controls, germ-free Rab11a-deficient mouse intestines failed to tolerate the
      intraluminal stimulation of microbial agonists. Thus, Rab11a endosome controls
      intestinal host-microbial homeostasis at least partially via sorting TLRs. 

PMID- 25063679
TI  - Rapid detection and identification of strains carrying carbapenemases directly
      from positive blood cultures using MALDI-TOF MS.
AB  - MALDI-TOF MS has been evaluated to detect carbapenemases activity and pathogen
      identification directly from positive blood cultures. 21 non-carbapenemase
      producers and 19 carbapenemase producers Enterobacteriaceae and Pseudomonas
      aeruginosa strains were included in the study. This technique is simple and
      detects carbapenemases in 4.5h with high sensitivity and specificity. 

PMID- 25063680
TI  - A systematic review of oral health behavior research in american adolescents.
AB  - Despite improvements in prevention, oral diseases are a problem among
      adolescents, linked to poor health outcomes and poor school performance. Little
      is known about adolescent oral health behavior. This systematic review describes
      factors that influence oral health behavior in adolescents. Inclusion criteria
      for the literature search were American children aged 12-19 and research on oral
      health behavior. Articles (n = 353) were retrieved, eight met the inclusion
      criteria, and of these, six were descriptive and two were experimental studies.
      The matrix method, critical appraisal, and content analysis produced themes
      across the studies. Participants were primarily African Americans and Hispanics
      of both genders, of lower socioeconomic status, aged 12-19. Findings suggest that
      ethnicity, race, and gender may influence oral health behavior in adolescents and
      that interventions have an effect. Research is needed to explore what other
      factors may influence oral health behavior in adolescents, long-term health
      outcomes, and school performance. 

PMID- 25063681
TI  - Statistical methods for incomplete data: Some results on model misspecification.
AB  - Inverse probability weighted estimating equations and multiple imputation are two
      of the most studied frameworks for dealing with incomplete data in clinical and
      epidemiological research. We examine the limiting behaviour of estimators arising
      from inverse probability weighted estimating equations, augmented inverse
      probability weighted estimating equations and multiple imputation when the
      requisite auxiliary models are misspecified. We compute limiting values for
      settings involving binary responses and covariates and illustrate the effects of
      model misspecification using simulations based on data from a breast cancer
      clinical trial. We demonstrate that, even when both auxiliary models are
      misspecified, the asymptotic biases of double-robust augmented inverse
      probability weighted estimators are often smaller than the asymptotic biases of
      estimators arising from complete-case analyses, inverse probability weighting or
      multiple imputation. We further demonstrate that use of inverse probability
      weighting or multiple imputation with slightly misspecified auxiliary models can
      actually result in greater asymptotic bias than the use of naive, complete case
      analyses. These asymptotic results are shown to be consistent with empirical
      results from simulation studies.

PMID- 25063682
TI  - Surgical management of posterior glottic diastasis in children.
AB  - INTRODUCTION: The purpose of this study was to report our clinical experience in
      the surgical management of patients with posterior glottic diastasis (PGD)
      secondary to prolonged intubation and/or laryngotracheoplasty (LTP) during
      childhood. METHODS: We reviewed the charts of patients with a history of
      prolonged intubation and/or LTP who had undergone surgical correction for PGD at
      our institution between 2010 and 2014. We documented demographic data and
      pertinent information regarding medical and surgical histories. The Pediatric
      Voice Handicap Index (pVHI) and/or the Consensus Auditory-Perceptual Evaluation
      of Voice (CAPE-V) were used to assess patients both before and after undergoing
      treatment for voice disorders. RESULTS: Six patients met our inclusion criteria.
      With 1 exception, all patients with complete voice data demonstrated improvements
      in perceptual, patient-reported, and acoustic voice measures. There were no
      perioperative complications. CONCLUSION: Our case series demonstrates that
      operative intervention can lead to improved voice in carefully selected patients
      with PGD secondary to prolonged intubation and/or LTP during childhood. Patients
      exhibited postoperative improvement in loudness and vocal endurance; however,
      they also exhibited a degree of compromise in voice quality.

PMID- 25063683
TI  - Recalcitrant rhinosinusitis, innate immunity, and mannose-binding lectin.
AB  - BACKGROUND: Mannose-binding lectin (MBL) is a protein produced by the liver that
      participates in innate immunity by tagging the surface of microbes for
      opsonization. Mannose-binding lectin deficiency is present in 7% of the
      population and has been implicated in recurrent respiratory tract infections in
      children. Mannose-binding lectin deficiency has not been explored in
      rhinosinusitis but is associated with increased mortality in adult pneumococcal
      infection. The purpose of this report is to describe a tertiary rhinology patient
      experience with MBL deficiency and recalcitrant rhinosinusitis. METHODS: This
      retrospective case series report characterizes predominantly adult patients with
      low MBL levels from January 2010 to June 2012. Indications for MBL testing, sinus
      culture data, immunological testing results, and treatments used to control
      rhinosinusitis are described. RESULTS: Mannose-binding lectin levels were
      deficient in 12 of 36 patients (33.3%) tested. IgG subclasses were abnormally low
      in 5 of 12 patients; IgA was normal in 11 of 12 patients; and IgM was normal in
      11 of 12 patients. Staphylococcus aureus, coagulase-negative Staphylococcus
      species, and Pseudomonas aeruginosa, known to be "tagged" by MBL, were the most
      common organisms grown on culture. Treatments included culture directed systemic
      antimicrobial therapy and topical steroids/antibiotics. CONCLUSION: Mannose
      binding lectin, an important component of the lectin complement pathway and
      innate immunity, is possibly associated with recalcitrant adult rhinosinusitis.
      Steroid/antibiotic irrigations appear to benefit patients with recalcitrant
      rhinosinusitis and possibly those with MBL deficiency. Given that the prevalence
      of MBL deficiency in this case series is 4 times that seen in the normal
      population, additional investigations are warranted to further elucidate the role
      of MBL deficiency in rhinosinusitis.

PMID- 25063684
TI  - Narcissistic Symptoms in German School Shooters.
AB  - School shooters are often described as narcissistic, but empirical evidence is
      scant. To provide more reliable and detailed information, we conducted an
      exploratory study, analyzing police investigation files on seven school shootings
      in Germany, looking for symptoms of narcissistic personality disorder as defined
      by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) in
      witnesses' and offenders' reports and expert psychological evaluations. Three out
      of four offenders who had been treated for mental disorders prior to the offenses
      displayed detached symptoms of narcissism, but none was diagnosed with
      narcissistic personality disorder. Of the other three, two displayed narcissistic
      traits. In one case, the number of symptoms would have justified a diagnosis of
      narcissistic personality disorder. Offenders showed low and high self-esteem and
      a range of other mental disorders. Thus, narcissism is not a common
      characteristic of school shooters, but possibly more frequent than in the general
      population. This should be considered in developing adequate preventive and
      intervention measures. 

PMID- 25063685
TI  - General Theory versus ENA Theory: Comparing Their Predictive Accuracy and Scope.
AB  - General theory attributes criminal behavior primarily to low self-control,
      whereas evolutionary neuroandrogenic (ENA) theory envisions criminality as being
      a crude form of status-striving promoted by high brain exposure to androgens.
      General theory predicts that self-control will be negatively correlated with risk
      taking, while ENA theory implies that these two variables should actually be
      positively correlated. According to ENA theory, traits such as pain tolerance and
      muscularity will be positively associated with risk-taking and criminality while
      general theory makes no predictions concerning these relationships. Data from
      Malaysia and the United States are used to test 10 hypotheses derived from one or
      both of these theories. As predicted by both theories, risk-taking was positively
      correlated with criminality in both countries. However, contrary to general
      theory and consistent with ENA theory, the correlation between self-control and
      risk-taking was positive in both countries. General theory's prediction of an
      inverse correlation between low self-control and criminality was largely
      supported by the U.S. data but only weakly supported by the Malaysian data. ENA
      theory's predictions of positive correlations between pain tolerance,
      muscularity, and offending were largely confirmed. For the 10 hypotheses tested,
      ENA theory surpassed general theory in predictive scope and accuracy.

PMID- 25063687
TI  - An IRT Analysis of the Symptoms of Major Depressive Disorder.
AB  - This study examines the psychometric properties of a major depressive episode
      using a large sample (N = 2,907) of outpatients with mood and anxiety disorders.
      A two-parameter logistic model yielded item threshold and discrimination
      parameters. A two-group confirmatory factor analysis was used to evaluate gender
      bias. Item thresholds fell along a continuum with the core features of depressed
      mood and anhedonia, along with fatigue, endorsed at lower levels of depression,
      and change in appetite and suicidal ideation endorsed at more severe levels. Item
      discriminations were highest for depressed mood and anhedonia, and lowest for
      change in appetite and suicidal ideation. The data indicate that the symptoms of
      depression assess a range of severity, with varying precision in discriminating
      depression. No gender differences were observed. Three exploratory symptom sets
      were compared with the full symptom set for depression, offering quantitative
      evidence that can be used to modify the psychiatric classification system. 

PMID- 25063686
TI  - Variation in the BDNF gene interacts with age to predict mortality in a
      prospective, longitudinal cohort with severe TBI.
AB  - BACKGROUND: Mortality predictions following traumatic brain injury (TBI), and our
      understanding of TBI pathology, may be improved by including genetic risk in
      addition to traditional prognostic variables. One promising target is the gene
      coding for brain-derived neurotrophic factor (BDNF), a ubiquitous neurotrophin
      important for neuronal survival and neurogenesis. OBJECTIVE: We hypothesized the
      addition of BDNF genetic variation would improve mortality prediction models and
      that BDNF Met-carriers (rs6265) and C-carriers (rs7124442) would have the highest
      mortality rates post-TBI. METHODS: This study examined BDNF functional single
      nucleotide polymorphisms rs6265 (val66met) and rs7124442 (T>C) in relation to
      mortality in a prospective, longitudinal cohort with severe TBI. We examined 315
      individuals receiving care for a closed head injury within the University of
      Pittsburgh Medical Center, aged 16 to 74 years. Mortality was examined acutely (0
      7 days postinjury) and postacutely (8-365 days postinjury). A gene risk score
      (GRS) was developed to examine both BDNF loci. Cox proportional hazards models
      were used to calculate hazard ratios for survivability post-TBI while controlling
      for covariates. RESULTS: BDNF GRS was significantly associated with acute
      mortality, regardless of age. Interestingly, subjects in the hypothesized no-risk
      allele group had the lowest survival probability. Postacutely, BDNF-GRS
      interacted with age such that younger participants in the no-risk group had the
      highest survival probability, while older participants in the hypothesized no
      risk group had the lowest probability of survival. CONCLUSIONS: These data
      suggest complex relationships between BDNF and TBI mortality that interact with
      age to influence survival predictions beyond clinical variables alone. Evidence
      supporting dynamic, temporal balances of pro-survival/pro-apoptotic target
      receptors may explain injury and age-related gene associations.

PMID- 25063688
TI  - Fungal biodegradation of dibutyl phthalate and toxicity of its breakdown products
      on the basis of fungal and bacterial growth.
AB  - Phthalates are esters of phthalic acid that give flexibility to polyvinyl
      chloride. Diverse studies have reported that these compounds might be
      carcinogenic, mutagenic and/or teratogenic. Radial growth rate, biomass, hyphal
      thickness of Neurospora sitophyla, Trichoderma harzianum and Aspergillus niger,
      grown in two different concentrations of dibutyl phthalate (DBP) (500 and 1,000
      mg/l) in agar and in submerged fermentation were studied. The inhibitory
      concentration (IC50) and the constant of biodegradation of dibutyl phthalate in
      Escherichia coli cultures were used to evaluate toxicity. The radial growth rate
      and thickness of the hypha were positively correlated with the concentration of
      phthalate. The pH of the cultures decreased as the fermentation proceeded. It is
      shown that these fungi are able to degrade DBP to non-toxic compounds and that
      these can be used as sole carbon and energy sources by this bacterium. It is
      demonstrated that the biodegradation of the DBP is directly correlated with the
      IC50. This is the first study that reports a method to determine the
      biodegradation of DBP on the basis of the IC50 and fungal growth, and the effect
      of this phthalate on the growth and thickness of hyphae of filamentous fungi in
      agar and in submerged fermentation.

PMID- 25063689
TI  - Concurrent quantitative HPLC-mass spectrometry profiling of small selenium
      species in human serum and urine after ingestion of selenium supplements.
AB  - Selenium metabolic patterns in the human body originating from five distinct
      selenium dietary sources, selenate, selenite, selenomethionine (SeMet),
      methylselenocysteine (MeSeCys) and selenized yeast, were investigated by
      performing concurrent HPLC-mass spectrometric analysis of human serum and urine.
      Total selenium and selenium species time profiles were generated by sampling and
      analyzing serum and urine from volunteers treated with selenium supplements, up
      to 5 and 24h following ingestion, respectively. We found that an increase in
      total serum selenium levels, accompanied by elevated selenium urinary excretion,
      was the common pattern for all treatments, except for that of selenite
      supplementation. Selenosugar 1 was a universal serum metabolite in all
      treatments, indicating that ingested selenium is favorably metabolized to the
      sugar. Except for selenite and selenized yeast ingestion, these patterns were
      reflected in the urine time series of the different treatments. Selenosugar 1 was
      the major selenium species present in urine in all treatments except for the
      selenate treatment, accounting for about 80% of the identified excreted species
      within 24h of ingestion. Furthermore, the urinary metabolite trimethylselenonium
      ion (TMSe) was detected for the first time in human background serum by using
      HPLC coupled to elemental and molecular mass spectrometry. The concurrent
      monitoring of non-protein selenium species in both body fluids provides the
      relation between bioavailability and excretion of the individual ingested species
      and of their metabolic products, while the combined use of elemental and
      molecular mass spectrometry enables the accurate quantitation of structurally
      confirmed species. This successfully applied approach is anticipated to be a
      useful tool for more extensive future studies into human selenium metabolism. 

PMID- 25063690
TI  - Update on human health effects of boron.
AB  - In vitro, animal, and human experiments have shown that boron is a bioactive
      element in nutritional amounts that beneficially affects bone growth and central
      nervous system function, alleviates arthritic symptoms, facilitates hormone
      action and is associated with a reduced risk for some types of cancer. The
      diverse effects of boron suggest that it influences the formation and/or activity
      of substances that are involved in numerous biochemical processes. Several
      findings suggest that this influence is through the formation of boroesters in
      biomolecules containing cis-hydroxyl groups. These biomolecules include those
      that contain ribose (e.g., S-adenosylmethionine, diadenosine phosphates, and
      nicotinamide adenine dinucleotide). In addition, boron may form boroester
      complexes with phosphoinositides, glycoproteins, and glycolipids that affect cell
      membrane integrity and function. Both animal and human data indicate that an
      intake of less than 1.0mg/day inhibits the health benefits of boron. Dietary
      surveys indicate such an intake is not rare. Thus, increasing boron intake by
      consuming a diet rich in fruits, vegetables, nuts and pulses should be recognized
      as a reasonable dietary recommendation to enhance health and well-being. 

PMID- 25063691
TI  - Double trouble, stick to the basics should be the rule!

PMID- 25063692
TI  - Does the presence of Q waves on the EKG accurately predict prior myocardial
      infarction when compared to cardiac magnetic resonance using late gadolinium
      enhancement? A cross-population study of noninfarct vs infarct patients.
AB  - BACKGROUND: We hypothesize that infarct detection by electrocardiogram (EKG) is
      inaccurate as compared with detection by magnetic resonance imaging and is
      potentially independent of infarct vs noninfarct status. This might have
      implications for societies in which initial cardiovascular testing is uniformly
      EKG. OBJECTIVE: This study aimed to relate EKG-defined scar to cardiovascular
      magnetic resonance imaging (CMR)-defined scar independent of the underlying
      myocardial pathology. METHODS: A total of 235 consecutive patients who underwent
      CMR-late gadolinium enhancement (LGE) with simultaneous EKG were screened for Q
      waves and compared with patients with a positive LGE pattern. The patients were
      divided into 3 groups: (1) patients with a positive infarct LGE pattern (LGE+/+;
      herein defined as LGE+), (2) patients with a noninfarct LGE pattern (LGE+/-), and
      (3) patients with a negative LGE pattern (LGE-). RESULTS: While 139 of 235
      patients (59%) were either LGE+ or LGE+/-, pathological Q waves were present in
      only 74 of 235 patients (31%). However, of these LGE+ or LGE+/- patients, only 76
      (32%) had an infarct LGE pattern representing little overlap between the presence
      of LGE+ and Q waves. EKG sensitivity and specificity to detect infarct: 66% and
      85%, respectively. However, of 24 of 74 patients (32%) with Q waves on the EKG,
      66% were LGE+/- and 34% were LGE-. Importantly, 3-dimensional volume of
      myocardial scar was far more predictive of a Q wave than of scar transmurality.
      CONCLUSION: EKG-defined scar, while ubiquitous for an infarct, has low
      sensitivity than CMR-LGE-defined scar. Unexpectedly, a significant number of
      pathological Q waves had absent infarct etiology, indicating high false
      positivity. Similarly, underrecognition of bona fide myocardial infarction
      frequently occurs, while 3-dimensional CMR volume of myocardial scar is far more
      predictive of a Q wave than of scar transmurality. This suggests that the well
      regarded EKG may be a disservice when applied on a population basis, leading to
      inappropriate over or under downstream testing with wide socioeconomic
      implications.

PMID- 25063694
TI  - Endovascular therapy of extracranial carotid artery pseudoaneurysms: case series
      and literature review.
AB  - BACKGROUND: Experience with endovascular therapy of extracranial carotid artery
      pseudoaneurysm (ECAP) has been growing, and various results suggest it as a
      suitable treatment option. We present a consecutive case series of patients with
      ECAPs treated with endovascular therapy, and a pertinent literature review.
      METHODS: A prospectively maintained database of neuroendovascular procedures was
      retrospectively reviewed for cases of ECAP treated between January 2007 and
      December 2012. The primary outcome of interest was incidence of periprocedural
      (within 30 days) neurologic and cardiopulmonary complications. PubMed was
      searched for relevant endovascular studies from 2000 to 2012 for the review.
      RESULTS: In our series, 12 patients with 14 ECAPs received stents, with or
      without coils. No perioperative neurologic or cardiopulmonary complications
      occurred. Median duration of clinical follow-up was 6.25 months (range 0-50
      months), and median duration of imaging follow-up was 6.25 months (range 0-50
      months), with eight patients asymptomatic and three showing improved symptoms
      (one patient with two lesions was lost to follow-up). Literature review revealed
      an overall primary outcome of 8.6% and no procedure related deaths. CONCLUSIONS:
      Endovascular treatment of ECAP is safe and effective at improving symptoms. There
      were no perioperative or permanent neurologic sequelae in the 11 patients with
      follow-up, and all symptomatology related to ECAP improved or resolved with
      treatment.

PMID- 25063695
TI  - Onyx embolization of an avulsed thalamoperforator following endoscopic colloid
      cyst and lamina terminalis fenestration.
AB  - A patient presented with headaches and was found to have a colloid cyst in the
      third ventricle and ventriculomegaly. The patient underwent endoscopic colloid
      cyst resection and third ventriculostomy without incidence. Prior to emergence, a
      blown right pupil was acutely noted, and bright red blood emanated from the
      ventricular drain that was routinely placed in the endoscopy tract at the
      conclusion of the procedure. CTangiography demonstrated active extravasation from
      the pre-pontine cistern into the third ventricle and subarachnoid space.
      Emergency DSA confirmed active extravasation from an avulsed thalamoperforator
      arising from the proximal right P1 posterior cerebral artery, which was
      immediately embolized without incident. 

PMID- 25063696
TI  - Immunohistochemical analysis of a ruptured basilar top aneurysm autopsied 22
      years after embolization with Guglielmi detachable coils.
AB  - The authors report on the histologic and immunohistochemical analyses of a
      cerebral aneurysm embolized with platinum coils and with the longest observation
      period. A 58-year-old woman presenting with subarachnoid hemorrhage due to
      ruptured basilar top aneurysm was treated with Guglielmi detachable coils (GDC)
      22 years ago. She was the 15th case since the GDC was introduced. After she died
      of unrelated causes, an autopsy and thorough histologic examination were
      performed. Gross examination revealed no adhesion between the aneurysm wall and
      the surrounding brain tissue. Histologic and immunohistochemical analyses
      demonstrated that the cavity of the aneurysm was filled with homogeneous
      collagenous fibrous tissue, while the neck was completely covered by a dense
      collagenous neointima and a smooth muscle cell layer. The unique histologic
      results of this case may contribute to a better understanding of the long-term
      evolution of the healing process in intracranial aneurysms successfully treated
      with the GDC. 

PMID- 25063697
TI  - Spontaneous closure of a dural arteriovenous fistula.
AB  - Spontaneous closure of a dural arteriovenous fistula (dAVF) is a rare condition
      and only a few cases have been reported since its first description in 1976. We
      report delayed and progressive spontaneous closure of a dAVF after massive
      intracerebral hemorrhage documented by angiographic studies before and after
      bleeding. To our knowledge, this is the first report to document gradual closure
      of a dAVF by serial angiographic studies. The mechanism of spontaneous closure of
      dAVFs has not been fully elucidated. We suggest different factors for
      consideration from previously published data and show how each of these factors
      can influence the others. 

PMID- 25063693
TI  - Principles of targeting endothelial cell metabolism to treat angiogenesis and
      endothelial cell dysfunction in disease.
AB  - The endothelium is the orchestral conductor of blood vessel function.
      Pathological blood vessel formation (a process termed pathological angiogenesis)
      or the inability of endothelial cells (ECs) to perform their physiological
      function (a condition known as EC dysfunction) are defining features of various
      diseases. Therapeutic intervention to inhibit aberrant angiogenesis or ameliorate
      EC dysfunction could be beneficial in diseases such as cancer and cardiovascular
      disease, respectively, but current strategies have limited efficacy. Based on
      recent findings that pathological angiogenesis and EC dysfunction are accompanied
      by EC-specific metabolic alterations, targeting EC metabolism is emerging as a
      novel therapeutic strategy. Here, we review recent progress in our understanding
      of how EC metabolism is altered in disease and discuss potential metabolic
      targets and strategies to reverse EC dysfunction and inhibit pathological
      angiogenesis. 

PMID- 25063698
TI  - Guar gum solutions for improved delivery of iron particles in porous media (part
      2): iron transport tests and modeling in radial geometry.
AB  - In the present work column transport tests were performed in order to study the
      mobility of guar-gum suspensions of microscale zero-valent iron particles (MZVI)
      in porous media. The results were analyzed with the purpose of implementing a
      radial model for the design of full scale interventions. The transport tests were
      performed using several concentrations of shear thinning guar gum solutions as
      stabilizer (1.5, 3 and 4g/l) and applying different flow rates (Darcy velocity in
      the range 1.10(-4) to 2.10(-3)m/s), representative of different distances from
      the injection point in the radial domain. Empirical relationships, expressing the
      dependence of the deposition and release parameters on the flow velocity, were
      derived by inverse fitting of the column transport tests using a modified version
      of E-MNM1D (Tosco and Sethi, 2010) and the user interface MNMs
      (www.polito.it/groundwater/software). They were used to develop a comprehensive
      transport model of MZVI suspensions in radial coordinates, called E-MNM1R, which
      takes into account the non Newtonian (shear thinning) rheological properties of
      the dispersant fluid and the porous medium clogging associated with filtration
      and sedimentation in the porous medium of both MZVI and guar gum residual
      undissolved particles. The radial model was run in forward mode to simulate the
      injection of MZVI dispersed in guar gum in conditions similar to those applied in
      the column transport tests. In a second stage, we demonstrated how the model can
      be used as a valid tool for the design and the optimization of a full scale
      intervention. The simulation results indicated that several concurrent aspects
      are to be taken into account for the design of a successful delivery of MZVI/guar
      gum slurries via permeation injection, and a compromise is necessary between
      maximizing the radius of influence of the injection and minimizing the injection
      pressure, to guarantee a sufficiently homogeneous distribution of the particles
      around the injection point and to prevent preferential flow paths. 

PMID- 25063699
TI  - Data quality assessment in the routine health information system: an application
      of the Lot Quality Assurance Sampling in Benin.
AB  - Health information systems in developing countries are often faulted for the poor
      quality of the data generated and for the insufficient means implemented to
      improve system performance. This study examined data quality in the Routine
      Health Information System in Benin in 2012 and carried out a cross-sectional
      evaluation of the quality of the data using the Lot Quality Assurance Sampling
      method. The results confirm the insufficient quality of the data based on three
      criteria: completeness, reliability and accuracy. However, differences can be
      seen as the shortcomings are less significant for financial data and for
      immunization data. The method is simple, fast and can be proposed for current use
      at operational level as a data quality control tool during the production stage. 

PMID- 25063700
TI  - [Importance of the interdisciplinary, evidence-based diagnosis of polycystic
      ovary syndrome].
AB  - Polycystic ovary syndrome is recognized as the most common hormonal and metabolic
      disorder of women. This heterogeneous endocrinopathy characterized by clinical
      and/or biochemical hyperandrogenism, oligo- or amenorrhoea, anovulatory
      infertility, and polycystic ovarian morphology. The prevalence, clinical feature
      and the risk of co-morbidity vary depending on the accuracy of the diagnosis and
      the criteria used. Evidence suggests that those women are at high risk who fulfil
      the criteria based on National Institute of Health. The complex feature of the
      syndrome and the considerable practice heterogeneity that is present with regards
      to diagnostic testing of patients who are suspected to have polycystic ovary
      syndrome require an interdisciplinary, evidence-based diagnostic approach. Such a
      method can ensure the patient safety and the effectiveness and efficiency of the
      diagnosis. This paper summarises the highest available evidence provided by well
      designed studies, meta-analysis and systematic reviews of the clinical feature
      and the clinical implications of the diagnostic criteria of polycystic ovary
      syndrome.

PMID- 25063701
TI  - [Late complications and treatment options of aortic coarctation operated in
      childhood].
AB  - INTRODUCTION: The prevalence of congenital aortic coarctation is 4 in 10 000 live
      birth. Aortic coarctation is typically located in the aortic isthmus, but it may
      occur at atypical sites. Treatment options include both surgical and endovascular
      interventions. In patients undergoing surgical or endovascular intervention late
      complications such as recoarctation or aortic aneurysm may develop. AIM: The aim
      of the authors was to analyse their own experience in late complication and
      treatment options of aortic coarctation operated in childhood. METHOD:
      Retrospective analysis of data of 32 patients treated between 1980 and 2014 for
      late complications 8-42 years after surgical treatment of aortic coarctation.
      RESULTS: In 28 patients aneurysm formation after isthmic patch plasty was found.
      Two patients had aortobronchial fistula, 2 patients showed anastomosis disruption
      and 2 patients had graft stenosis. During operation hybrid solution was performed
      in 23 patients, isthmic aorto-aortic inlay graft interposition in 5 patients,
      aorto-aortic bypass in 2 patients, subclavio-aortic bypass in 2 patients, graft
      patch plasty in one patient and ilio-renal bypass in one patient. Complications
      included severe intraoperative bleeding in one patient and pneumothorax in one
      patient. No early or late mortality occurred. CONCLUSIONS: The authors conclude
      that life long control is mandatory in order to detect late complications in
      patients who underwent operation of aortic coarctation in childhood.

PMID- 25063702
TI  - [Outcome of a one-year behavior therapy weight loss program].
AB  - INTRODUCTION: Treatment of obesity has become one of the most challenging issues.
      AIM: The aims of the authors were to present the results of standard behavior
      therapy weight loss program combined with self-help and the results of one-year
      follow-up. METHOD: The 24-week program involved 41 participants of which 33
      subjects participated in the follow-up. Anthropometric data were obtained and the
      participants were asked to fill questionnaires (the 21 items Three Factor Eating
      Questionnair Revised 21 items; Physical Exercise: Steps of change [Short Form].
      RESULTS: 87.8% of participants achieved a minimum weight loss of 5% which is the
      rate expected in professional therapies for obesity. Significant changes in
      maladaptive eating pattern and an increase in the rate of regular exercise were
      observed. Significant association was found between the increase of cognitive
      restraint and the rate of weight loss during treatment. At one-year follow-up the
      majority of participants (75.8%) did keep their minimum weight loss of 5% and
      they showed significant change in eating pattern. CONCLUSIONS: The results
      suggest that standard behavior therapy extended with self-help elements may be a
      cost-effective treatment of obesity.

PMID- 25063703
TI  - [Plasmapheresis in the treatment of hypertriglyceridemia].
AB  - The authors present the case of a 38-year-old woman with severe
      hypertriglyceridemia-induced acute recurrent pancreatitis (triglyceride 16 761
      mg/dl, 189.4 mmol/l). According to the knowledge of the authors, such a high
      triglyceride has not been previously reported in Hungarian and international
      scientific literature. The patient received conventional treatment (fluid
      replacement, analgesic, antibiotics, discontinuation of oral intake) and
      plasmapheresis too. After two sessions of plasmapheresis with one month interval
      the clinical and laboratory parameters greatly improved. Severe
      hypertriglyceridemia (triglyceride level more than 1000 mg/dl, ~11.3 mmol/l) is
      an independent risk factor for acute pancreatitis. Plasmapheresis seems to be
      safe and effective to rapidly decrease triglyceride levels and to remove the
      causative agent for pancreatitis in a patient with severe hypertriglyceridemia.

PMID- 25063704
TI  - [The placentophagy today].

PMID- 25063707
TI  - Immune derived opioidergic inhibition of viscerosensory afferents is decreased in
      Irritable Bowel Syndrome patients.
AB  - Alterations in the neuro-immune axis contribute toward viscerosensory nerve
      sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors
      secreted from immune cells inhibit colo-rectal afferents in health, and loss of
      this inhibition may lead to hypersensitivity and symptoms. We aimed to determine
      the immune cell type(s) responsible for opioid secretion in humans and whether
      this is altered in patients with IBS. The beta-endorphin content of specific
      immune cell lineages in peripheral blood and colonic mucosal biopsies were
      compared between healthy subjects (HS) and IBS patients. Peripheral blood
      mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to
      colo-rectal sensory afferent endings in mice with post-inflammatory chronic
      visceral hypersensitivity (CVH). beta-Endorphin was identified predominantly in
      monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina
      propria. Monocyte derived beta-endorphin levels and colonic macrophage numbers
      were lower in IBS patients than healthy subjects. PBMC supernatants from healthy
      subjects had greater inhibitory effects on colo-rectal afferent
      mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC
      supernatants were more prominent in CVH mice compared to healthy mice due to an
      increase in MU-opioid receptor expression in dorsal root ganglia neurons in CVH
      mice. Monocyte/macrophages are the predominant immune cell type responsible for
      beta-endorphin secretion in humans. IBS patients have lower monocyte derived beta
      endorphin levels than healthy subjects, causing less inhibition of colonic
      afferent endings. Consequently, altered immune function contributes toward
      visceral hypersensitivity in IBS. 

PMID- 25063706
TI  - Xanomeline suppresses excessive pro-inflammatory cytokine responses through
      neural signal-mediated pathways and improves survival in lethal inflammation.
AB  - Inflammatory conditions characterized by excessive immune cell activation and
      cytokine release, are associated with bidirectional immune system-brain
      communication, underlying sickness behavior and other physiological responses.
      The vagus nerve has an important role in this communication by conveying sensory
      information to the brain, and brain-derived immunoregulatory signals that
      suppress peripheral cytokine levels and inflammation. Brain muscarinic
      acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated
      in this regulation. However, the possibility of controlling inflammation by
      peripheral administration of centrally-acting mAChR agonists is unexplored. To
      provide insight we used the centrally-acting M1 mAChR agonist xanomeline,
      previously developed in the context of Alzheimer's disease and schizophrenia.
      Intraperitoneal administration of xanomeline significantly suppressed serum and
      splenic TNF levels, alleviated sickness behavior, and increased survival during
      lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain
      mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The
      anti-inflammatory efficacy of xanomeline was retained for at least 20h,
      associated with alterations in splenic lymphocyte, and dendritic cell
      proportions, and decreased splenocyte responsiveness to endotoxin. These results
      highlight an important role of the M1 mAChR in a neural circuitry to spleen in
      which brain cholinergic activation lowers peripheral pro-inflammatory cytokines
      to levels favoring survival. The therapeutic efficacy of xanomeline was also
      manifested by significantly improved survival in preclinical settings of severe
      sepsis. These findings are of interest for strategizing novel therapeutic
      approaches in inflammatory diseases. 

PMID- 25063708
TI  - Toll-like receptors in central nervous system injury and disease: a focus on the
      spinal cord.
AB  - Toll-like receptors (TLRs) are best known for recognizing pathogens and
      initiating an innate immune response to protect the host. However, they also
      detect tissue damage and induce sterile inflammation upon the binding of
      endogenous ligands released by stressed or injured cells. In addition to immune
      system-related cells, TLRs have been identified in central nervous system (CNS)
      neurons and glial subtypes including microglia, astrocytes and oligodendrocytes.
      Direct and indirect effects of TLR ligands on neurons and glial subtypes have
      been documented in vitro. Likewise, the effects of TLR ligands have been
      demonstrated in vivo using animal models of CNS trauma and disease including
      spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS) and neuropathic
      pain. The indirect effects are most likely mediated via microglia or immune
      system cells that infiltrate the diseased or injured CNS. Despite considerable
      progress over the past decade, the role of TLRs in the physiological and
      pathological function of the spinal cord remains inadequately defined. Published
      reports collectively highlight TLRs as promising targets for therapeutic
      interventions in spinal cord pathology. The findings also underscore the
      complexity of TLR-mediated mechanisms and the necessity for further research in
      this field. The goals of the current review are to recapitulate the studies that
      investigated the role of TLRs in the spinal cord, to discuss potential future
      research directions, and to examine some of the challenges associated with pre
      clinical studies pertinent to TLRs in the injured or diseased spinal cord. 

PMID- 25063709
TI  - Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the
      mouse.
AB  - Post-septic encephalopathy is a poorly understood condition in survivors of
      sepsis that is characterised by cognitive and affective impairments. In this
      study we have sought to better understand this condition by undertaking a
      comprehensive behavioural and cognitive assessment of mice who had previously
      survived sepsis. Mice were treated with lipopolysaccharide (LPS; 5mg/kg) and one
      month after this assessed on a battery of tests. Post-septic animals were found
      to display significantly more immobility in the tail suspension test and show a
      significantly decreased sucrose preference. Acute fluoxetine treatment reversed
      the increase in immobility in the tail suspension test in post-septic animals.
      Post-septic animals also showed less overall exploratory behaviour in the novel
      object recognition task and also showed increased anxiety-like behaviour in the
      elevated plus maze. Post-septic mice did not show signs of cognitive impairment,
      as assessed in the Morris watermaze, the 8-arm radial maze or on preference for
      the novel object in the novel object recognition task. Immunohistochemical
      analysis revealed significant upregulation of the microglial marker CD-11b, F4/80
      and IBA-1 in the hippocampus of post-septic animals, as well as significant
      downregulation of the plasticity-related immediate early gene products ARC and
      EGR1. We also observed a decrease in neural stem cell proliferation in the
      dentate gyrus of post-septic animals as judged by BrdU incorporation. Co
      treatment with the NF-kappaB pathway inhibitor PDTC attenuated the long-lasting
      effects of LPS on most of the affected parameters, but not on neural stem cell
      proliferation. These results show that LPS-induced sepsis in the mouse is
      followed by long-lasting increases in depressive- and anxiety-like behaviours, as
      well as by changes in neuroinflammatory- and neural plasticity-associated
      factors, and that attenuation of the severity of sepsis by PDTC attenuates many
      of these effects. 

PMID- 25063710
TI  - Protective effect of sanguinarine on LPS-induced endotoxic shock in mice and its
      effect on LPS-induced COX-2 expression and COX-2 associated PGE2 release from
      peritoneal macrophages.
AB  - The quaternary ammonium salt, sanguinarine (SG) was reported to possess
      widespread anti-microbial and anti-inflammatory effects in experimental animals
      and it has been used to treat many inflammatory diseases. The aim of this study
      was to evaluate the anti-inflammatory effect and the possible mechanisms
      underlying the anti-inflammatory activity of SG. Experimentally-induced mice ES
      model and LPS-induced peritoneal macrophages were used to examine the anti
      inflammatory function of SG. In this study, SG pretreatment significantly
      increased the survival rate of mice from 25% to 58%, 75% and 91% respectively.
      The production of PGE2 in BALF, the lung MPO activity and the (W/D) weight ratios
      were also markedly reduced. In addition, immunohistochemical analysis showed that
      the expression of COX-2 was significantly suppressed in vivo. We also evaluated
      the effect of SG in LPS-induced peritoneal macrophages to clarify the possible
      mechanism. The data indicated that SG greatly inhibited the production of PGE2,
      and it also decreased COX-2 protein expression, without affecting COX-1
      expression, in LPS-stimulated peritoneal macrophages. Taken all together, SG
      potently protected against LPS-induced ES, and our results suggest that the
      possible mechanism may be relevant to COX-2 regulation. 

PMID- 25063711
TI  - Protective effect of catalpol on lipopolysaccharide-induced acute lung injury in
      mice.
AB  - Catalpol, an iridiod glucoside isolated from Rehmannia glutinosa, has been
      reported to have anti-inflammatory properties. Although anti-inflammatory
      activity of catalpol already reported, its involvement in lung protection has not
      been reported. Thus, we investigated the role of catalpol on lipopolysaccharide
      (LPS)-induced acute lung injury in this study. Mice acute lung injury model was
      induced by intranasal instillation of LPS. Catalpol was administrated 1h prior to
      or after LPS exposure. The severity of pulmonary injury was evaluated 12h after
      LPS administration. The results showed that catalpol inhibited lung W/D ratio,
      myeloperoxidase activity of lung samples, the amounts of inflammatory cells and
      TNF-alpha, IL-6, IL-4 and IL-1beta in BALF induced by LPS. The production of IL
      10 in BALF was up-regulated by catalpol. In vitro, catalpol inhibited TNF-alpha,
      IL-6, IL-4 and IL-1beta production and up-regulated IL-10 expression in LPS
      stimulated alveolar macrophages. Moreover, western blot analysis showed that the
      activation of NF-kappaB and MAPK signaling pathways was inhibited by catalpol.
      Furthermore, catalpol was found to inhibit TLR4 expression induced by LPS. In
      conclusion, catalpol potently protected against LPS-induced ALI. The protective
      effect may attribute to the inhibition of TLR4-mediated NF-kappaB and MAPK
      signaling pathways. 

PMID- 25063712
TI  - Mercury concentrations in forest soils and stream waters in northeast and south
      China.
AB  - Atmospheric deposition of mercury (Hg) is generally higher in China than in North
      America and Europe. Transport and methylation of Hg deposited in forest
      ecosystems may cause health risks to humans. We collected water samples from 117
      small streams, and soil samples from 25 sites in forested areas in northeast and
      south China during 2011-2013 to investigate the spatial distribution of Hg.
      Results showed that Hg concentration in surface soil (0-5 cm in depth) was
      generally higher in south China (97.8 +/- 36.0 MUg/kg) than that in the northeast
      (44.0 +/- 14.1 MUg/kg). In contrast, the Hg concentration in stream water was
      higher in northeast China (17.2 +/- 11.0 ng/L) than that in the south (6.2 +/-
      6.4 ng/L). Hg concentrations in surface soil were positively correlated with Hg
      concentrations in the overlying litter Oe/Oa horizon (r(2)=0.84). Hg
      concentrations in stream water were positively correlated to DOC (dissolved
      organic carbon) concentrations (r(2)=0.43) and to the Hg concentration in the
      litter Oe/Oa horizon (r(2)=0.69). Because the litter Oe/Oa horizon represents Hg
      accumulated by foliage, the positive correlations indicate that atmospheric Hg
      deposition was an important factor affecting Hg concentrations in soils and
      stream water.

PMID- 25063713
TI  - Mineral oil in human tissues, part II: characterization of the accumulated
      hydrocarbons by comprehensive two-dimensional gas chromatography.
AB  - Mineral oil hydrocarbons are by far the largest contaminant in the human body.
      Their composition differs from that in the mineral oils humans are exposed to,
      and varies also between different tissues of the same individual. Using the
      presently best technique for characterizing the composition of mineral oil
      hydrocarbons, comprehensive two-dimensional gas chromatography (GC*GC), the
      hydrocarbons in human tissues were compared to those of various mineral oils.
      This provided information about the strongly accumulated species and might give
      hints on the flow path through the human body. The selectivity of accumulation is
      probably also of interest for the risk assessment of synthetic hydrocarbons
      (polyolefins). GC*GC grouped the MOSH into classes of n-alkanes, paraffins with a
      low degree of branching, multibranched paraffins and naphthenes (alkylated cyclic
      hydrocarbons) with 1-4 rings. Metabolic elimination was observed for constituents
      of all these classes, but was selective within each class. The MOSH in the
      subcutaneous abdominal fat tissues and the mesenteric lymph nodes (MLN) had
      almost the same composition and included the distinct signals observed in mineral
      oil, though in reduced amounts relative to the cloud of unresolved hydrocarbons.
      The MOSH in the liver and the spleen were different from those in the MLN and fat
      tissue, but again with largely identical composition for a given individual.
      Virtually all constituents forming distinct signals were eliminated, leaving an
      unresolved residue of highly isomerized hydrocarbons.

PMID- 25063714
TI  - Youth health care, where to start?

PMID- 25063715
TI  - Development and validation of the diabetes adolescent problem solving
      questionnaire.
AB  - OBJECTIVE: Problem solving is a critical diabetes self-management skill. Because
      of a lack of clinically feasible measures, our aim was to develop and validate a
      self-report self-management problem solving questionnaire for adolescents with
      type 1 diabetes (T1D). METHODS: A multidisciplinary team of diabetes experts
      generated questionnaire items that addressed diabetes self-management problem
      solving. Iterative feedback from parents and adolescents resulted in 27 items.
      Adolescents from two studies (N=156) aged 13-17 were recruited through a
      pediatric diabetes clinic and completed measures through an online survey.
      Glycemic control was measured by HbA1c recorded in the medical record. RESULTS:
      Empirical elimination of items using principal components analyses resulted in a
      13-item unidimensional measure, the diabetes adolescent problem solving
      questionnaire (DAPSQ) that explained 56% of the variance. The DAPSQ demonstrated
      internal consistency (Cronbach's alpha=0.92) and was correlated with diabetes
      self-management (r=0.53, p<.001), self-efficacy (r=0.54, p<.001), and glycemic
      control (r=-0.24, p<.01). CONCLUSION: The DAPSQ is a brief instrument for
      assessment of diabetes self-management problem solving in youth with T1D and is
      associated with better self-management behaviors and glycemic control. PRACTICE
      IMPLICATIONS: The DAPSQ is a clinically feasible self-report measure that can
      provide valuable information regarding level of self-management problem solving
      and guide patient education.

PMID- 25063716
TI  - Psychiatric disorders and function in adolescents with d-transposition of the
      great arteries.
AB  - OBJECTIVE: To compare adolescents with d-transposition of the great arteries (d
      TGA) with healthy adolescents with respect to prevalence of psychiatric disorders
      and global psychosocial functioning. STUDY DESIGN: Subjects, consisting of 139
      adolescents with d-TGA (16.1 +/- 0.5 years) and 61 healthy adolescents (15.3 +/-
      1.1 years) without known risk factors for brain disorders, underwent a battery of
      assessments, including semistructured psychiatric interviews; self-report
      measures of depressive, anxiety, and disruptive behavior symptoms; and brain
      magnetic resonance imaging. Previous cognitive functioning and parental stress
      assessments at age 8 as well as parental post-traumatic stress at age 16 years
      were explored as potential risk factors predictive of overall psychiatric
      functioning. RESULTS: Compared with healthy adolescents, adolescents with d-TGA
      had higher lifetime prevalence of structured interview-derived attention
      deficit/hyperactivity disorder (19% vs 7%, P = .03), along with reduced global
      psychosocial functioning (80.6 +/- 11.2 vs 87.2 +/- 7.1, P < .001) as well as
      significant increases in self-reported depressive (P = .01), anxiety (P = .02),
      and disruptive behavior symptoms (parent P < .001 and adolescent P = .03).
      Nevertheless, these youth scored in the nonclinical range on all self-report
      measures. Level of global psychosocial functioning was positively related to
      cognitive functioning (P < .001) and negatively related to parental stress (P =
      .008). CONCLUSIONS: Although adolescents with d-TGA demonstrate significant
      resilience to known neuropsychological and academic deficits, they show increased
      rates of attention-deficit/hyperactivity disorder and reduced psychosocial
      functioning. Impaired cognitive functioning and parental stress at younger age
      emerged as significant risk factors for psychiatric impairment.

PMID- 25063717
TI  - Antithrombotic therapy for secondary stroke prevention in bacterial meningitis in
      children.
AB  - OBJECTIVE: To assess the safety and efficacy of antithrombotic therapy (ATT) for
      secondary stroke prevention of childhood bacterial meningitis. STUDY DESIGN: A
      retrospective study of cases of stroke associated with bacterial meningitis in 2
      pediatric hospitals during a period of 15 years. Patients were included in the
      study if they were between 28 days and 18 years of age and had at least 2 serial
      neuroimaging studies during the acute phase of their illness. The safety of ATT
      was assessed by the presence or absence of intracranial hemorrhage. Efficacy was
      assessed by the failure in preventing stroke recurrence. Neurologic outcome was
      determined by the last documented Pediatric Stroke Outcome Measure score.
      RESULTS: Twenty-two cases of childhood bacterial meningitis complicated by stroke
      were identified. Six cases were treated with heparin after either initial or
      recurrent infarction. None of the cases receiving heparin had further recurrence.
      Aspirin (acetylsalicylic acid [ASA]) was started after the initial or after
      recurrent infarction in 10 cases. Four (40%) had infarctions on ASA; 3 of these
      patients subsequently received heparin. In the 14 cases in which no ATT was
      begun, 8 (57%) had further recurrence of infarction. None of the patients,
      whether receiving heparin or ASA, had intracranial hemorrhage. CONCLUSION: In
      this small sample, heparin and ASA appeared to be safe in childhood bacterial
      meningitis complicated by stroke and may be effective in improving outcome.
      Heparin may be more effective than aspirin in preventing recurrent infarction.

PMID- 25063718
TI  - Association of urinary phenols with increased body weight measures and obesity in
      children and adolescents.
AB  - OBJECTIVE: To examine the association of urinary levels of the environmental
      phenol pesticides 2,5-dichlorophenol, 2,4-dichlorophenol, and triclosan with body
      weight outcomes in children and adolescent participants in the National Health
      and Nutrition Examination Survey 2007-2010. STUDY DESIGN: We performed
      multivariate linear and multinomial logistic regressions to analyze the
      association of body mass index (BMI) z-score, waist circumference (WC), and
      obesity with urinary pesticide concentration in children and adolescents.
      RESULTS: After adjustment for covariates, we found a statistically significant
      positive association (P < .05) between both 2,5-dichlorophenol and 2,4
      dichlorophenol with BMI z-score, WC, and obesity in children and adolescents.
      After stratification by age, the significant associations remained only in
      adolescents (ages 12-19). No associations were found between triclosan and any of
      the body weight outcomes. CONCLUSIONS: We found an association between
      dichlorophenols and increased body weight measures (BMI z-score, WC, and obesity)
      in adolescents. However, further studies, such as a longitudinal study, are
      needed to confirm and elucidate on our findings.

PMID- 25063719
TI  - Discrepant hepatitis B surface antigen results in pregnant women screened to
      identify hepatitis B virus infection.
AB  - OBJECTIVE: To resolve discrepant hepatitis B surface antigen (HBsAg) results for
      pregnant women screened for hepatitis B virus (HBV) infection. STUDY DESIGN: A
      case was defined as discrepant HBsAg (reactive followed by non-reactive) result
      during the same pregnancy. The Centers for Disease Control and Prevention
      examined a convenience sample of cases passively reported by US Perinatal
      Hepatitis B Prevention Programs. Using a standard form, available results were
      obtained for hepatitis B tests and vaccination histories. Results were
      independently reviewed by 3 viral hepatitis experts and a clinical virologist to
      resolve discrepancies. The initial HBsAg result was classified as probable true
      positive, probable false positive, or unresolved. RESULTS: From April 2009
      December 2011, 142 (75.9%) of 187 reported discrepant cases met the case
      definition. Of the 142 initial reactive HBsAg results, 113 (79.5%) were
      laboratory-confirmed, and 89 (62.7%) were resolved. Among these 89 cases, the
      initial test was a probable true positive in 14 (15.7%), and a false positive in
      75 (84.3%). Total antibody to hepatitis B core antigen was positive for 11
      (78.6%) of the true positive cases and negative for 67 (89.3%) of the false
      positive cases. True positives included 2 cases of resolving acute HBV infection
      and one case recently given hepatitis B vaccination. CONCLUSIONS: In this
      retrospective analysis of discrepant HBsAg-reactive screening results from
      pregnant women, the majority were false positives, but true positives occurred.
      Testing for total hepatitis B core antibody, an indicator of past or current HBV
      infection, was useful for resolving discrepancies.

PMID- 25063720
TI  - Harnessing the placebo effect in pediatric migraine clinic.

PMID- 25063721
TI  - Ultrasound evaluation of lumbar spine anatomy in newborn infants: implications
      for optimal performance of lumbar puncture.
AB  - An ultrasound evaluation of lumbar spine anatomic landmarks relevant for lumbar
      puncture was performed in 199 newborn infants. Effects of 6 patient positions and
      gestational age on interspinous process distance, subarachnoid space width,
      predicted needle entry angle, and needle insertion depth were assessed. Our
      results identify optimized conditions for lumbar puncture: sitting the infant
      with hips flexed, a needle entry angle of 65-70 degrees, and proper needle
      insertion depth (calculated as 2.5 * weight in kilograms + 6 in millimeters). 

PMID- 25063722
TI  - Quantity and timing of maternal prenatal smoking on neonatal body composition:
      the Healthy Start study.
AB  - OBJECTIVE: To examine the dose-dependent and time-specific relationships of
      prenatal smoking with neonatal body mass, fat mass (FM), fat-free mass (FFM), and
      FM-to-FFM ratio, as measured by air-displacement plethysmography (PEA POD
      system). STUDY DESIGN: We analyzed 916 mother-neonate pairs participating in the
      longitudinal prebirth cohort Healthy Start study. Maternal prenatal smoking
      information was collected in early, middle, and late pregnancy by self-report.
      Neonatal body composition was measured with the PEA POD system after delivery.
      Multiple general linear regression models were adjusted for maternal and neonatal
      characteristics. RESULTS: Each additional pack of cigarettes smoked during
      pregnancy was associated with significant decreases in neonatal body mass
      (adjusted mean difference, -2.8 g; 95% CI, -3.9 to -1.8 g; P < .001), FM (-0.7 g;
      95% CI, -1.1 to -0.3 g; P < .001), and FFM (-2.1 g; 95% CI, -2.9 to -1.3 g; P <
      .001). Neonates exposed to prenatal smoking throughout pregnancy had
      significantly lower body mass (P < .001), FM (P < .001), and FFM (P < .001)
      compared with those not exposed to smoking. However, neonates of mothers who
      smoked only before late pregnancy had no significant differences in body mass (P
      = .47), FM (P = .43), or FFM (P = .59) compared with unexposed offspring.
      CONCLUSION: Exposure to prenatal smoking leads to systematic growth restriction.
      Smoking cessation before late pregnancy may reduce the consequences of exposure
      to prenatal smoking on body composition. Follow-up of this cohort is needed to
      determine the influence of catch-up growth on early-life body composition and the
      risk of childhood obesity.

PMID- 25063723
TI  - Central nervous system complications of varicella-zoster virus.
AB  - OBJECTIVE: To describe the spectrum of central nervous system complications of
      varicella-zoster virus (VZV) in children admitted to The Hospital for Sick
      Children between January 1999 and December 2012. STUDY DESIGN: Children aged 1
      month to 18 years (n = 84) admitted with neurologic manifestations associated
      with a characteristic VZV rash or a confirmatory laboratory test (positive lesion
      scraping or cerebrospinal fluid polymerase chain reaction) were included in the
      study. Acute neurologic complications were included if they occurred within 4
      weeks of VZV infection. Stroke was considered related to VZV if it occurred
      within 6 months of VZV infection, the neuroimaging was characteristic, and other
      causes were excluded. RESULTS: Clinical syndromes included acute cerebellar
      ataxia (n = 26), encephalitis (n = 17), isolated seizures (n = 16), stroke (n =
      10), meningitis (n = 10), Guillain-Barre syndrome (n = 2), acute disseminated
      encephalomyelitis (n = 2), and Ramsay Hunt syndrome (n = 1). In those with acute
      complications (nonstroke), neurologic symptoms occurred a median of 5 days after
      rash onset (range -6 to +16). The time between rash onset and stroke ranged from
      2 weeks to 26 weeks (median 16.0 weeks). Three children with encephalitis died.
      Residual neurologic sequelae at one year occurred in 9 of 39 (23%) of children
      with follow-up data. Only 4 children were reported to have received the varicella
      vaccine. CONCLUSION: Neurologic complications of VZV infection continue to occur
      despite the availability of an effective vaccine. Neurologic symptom onset can
      predate the appearance of the VZV exanthem and in rare cases may occur in the
      absence of an exanthem.

PMID- 25063724
TI  - Fibroblast growth factor-23 in obese, normotensive adolescents is associated with
      adverse cardiac structure.
AB  - OBJECTIVES: Fibroblast growth factor-23 (FGF23) is a biomarker for cardiovascular
      disease. Obesity may promote FGF23 production in the absence of chronic kidney
      disease. We sought to determine among normotensive African American adolescents
      whether FGF23 levels are greater in obese compared with normal-weight adolescents
      and to determine the relationship of FGF23 with markers of cardiac structure and
      insulin resistance. STUDY DESIGN: Cross-sectional data were obtained from a
      cohort of 130 normotensive, African American adolescents ages 13-18 years without
      chronic kidney disease; 74 were obese; 56 were normal weight. Plasma C-terminal
      FGF23, fasting glucose and insulin, and high-sensitivity C-reactive protein were
      measured; participants underwent M-mode echocardiography. RESULTS: FGF23 was
      skewed and approximately normally distributed after natural log transformation
      (logFGF23). FGF23 levels were greater in obese vs normal-weight participants
      (geometric mean 43 vs 23 RU/mL, P < .01). FGF23 values were significantly greater
      in participants with eccentric or concentric cardiac hypertrophy compared with
      those without hypertrophy P < .01). LogFGF23 directly correlated with body mass
      index, body mass index z-score, waist circumference, fasting insulin levels, and
      homeostasis model assessment scores. Regression models adjusted for age, sex, and
      high-sensitivity C-reactive protein suggest that each 10% increase in FGF23 is
      associated with a 1.31 unit increase in left ventricular mass (P < .01), a 0.29
      unit increase in left ventricular mass index (P < .01), and a 0.01-unit increase
      in left atrial dimension indexed to height (P = .02). CONCLUSIONS: In this sample
      of obese African American adolescents, FGF23 blood levels were associated with
      abnormal cardiac structure. We postulate that FGF23 may be an early marker of
      cardiac injury in obese but otherwise-healthy African American adolescents.

PMID- 25063725
TI  - Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in
      premature newborns.
AB  - OBJECTIVE: To assess the efficacy and safety of early, noninvasive inhaled nitric
      oxide (iNO) therapy in premature newborns who do not require mechanical
      ventilation. STUDY DESIGN: We performed a multicenter randomized trial including
      124 premature newborns who required noninvasive supplemental oxygen within the
      first 72 hours after birth. Newborns were stratified into 3 different groups by
      birth weight (500-749, 750-999, 1000-1250 g) prior to randomization to iNO (10
      ppm) or placebo gas (controls) until 30 weeks postmenstrual age. The primary
      outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks
      postmenstrual age. Secondary outcomes included the need for and duration of
      mechanical ventilation, severity of BPD, and safety outcomes. RESULTS: There was
      no difference in the incidence of death or BPD in the iNO and placebo groups (42%
      vs 40%, P = .86, relative risk = 1.06, 0.7-1.6). BPD severity was not different
      between the treatment groups. There were no differences between the groups in the
      need for mechanical ventilation (22% vs 23%; P = .89), duration of mechanical
      ventilation (9.7 vs 8.4 days; P = .27), or safety outcomes including severe
      intracranial hemorrhage (3.4% vs 6.2%, P = .68). CONCLUSIONS: We found that iNO
      delivered noninvasively to premature infants who have not progressed to early
      respiratory failure is a safe treatment, but does not decrease the incidence or
      severity of BPD, reduce the need for mechanical ventilation, or alter the
      clinical course.

PMID- 25063726
TI  - Diet-induced maternal obesity alters ovarian morphology and gene expression in
      the adult mouse offspring.
AB  - OBJECTIVE: To examine the effects of high-fat (HF) diet-induced maternal obesity
      on follicular population and gene expression in adult offspring ovaries. DESIGN:
      Experimental mouse study. SETTING: Laboratory. ANIMAL(S): Mice on HF diet.
      INTERVENTION(S): Female C57BL/6J mice were fed an HF or standard chow (C) diet 6
      weeks before conception, through pregnancy and lactation. Offspring were fed the
      C or HF diet from weaning, creating the HF/HF, HF/C, C/HF, C/C offspring groups.
      MAIN OUTCOME MEASURE(S): Follicular counts and gene expression in adult offspring
      ovaries. RESULT(S): Prenatal exposure to maternal HF nutrition resulted in the
      reduction of primordial, antral, and Graafian follicle numbers in offspring
      ovaries (both HF/C and HF/HF). Expression levels of genes involved in apoptosis
      (FoXO3a), follicular growth and development (Gdf9), and circadian rhythms
      generation (Clock and Bmal1) were elevated in the ovaries of HF/C and HF/HF
      offspring, while expression of the circadian clock genes Cry1 and Per1 were lower
      in HF/HF ovaries. CONCLUSION(S): Maternal obesity during pregnancy has long-term
      deleterious consequences on follicular growth and development in the adult
      offspring ovaries, which may impact their reproductive potential.

PMID- 25063727
TI  - Human oocyte-derived sperm chemoattractant is a hydrophobic molecule associated
      with a carrier protein.
AB  - OBJECTIVE: To characterize the nature of the human oocyte-derived
      chemoattractant. DESIGN: Laboratory in vitro study. SETTING: Academic research
      institute. PATIENT(S): Ten healthy sperm donors. Oocyte-conditioned media from
      women undergoing IVF treatment because of male factor infertility.
      INTERVENTION(S): Sperm samples were processed by the migration-sedimentation
      technique. Oocyte-conditioned media were collected 2-3 hours after oocyte
      stripping. MAIN OUTCOME MEASURE(S): Sperm chemotaxis was assayed in a MU-slide
      chamber according to the direction of swimming relative to that of the chemical
      gradient. RESULT(S): Oocyte-conditioned media treated with proteases did not lose
      their chemotactic activity; on the contrary, they became more active, with the
      activity shifted to lower concentrations. When oocyte-conditioned media were
      subjected to hexane extraction, chemotactic activity was found in both the
      hydrophobic and aqueous phases. Known mammalian sperm chemoattractants were ruled
      out as oocyte-derived chemoattractants. CONCLUSION(S): Our results suggest that
      the oocyte-derived chemoattractant is a hydrophobic nonpeptide molecule that, in
      an oocyte-conditioned medium, is associated with a carrier protein that enables
      its presence in a hydrophilic environment.

PMID- 25063728
TI  - Methylation status of human chorionic gonadotropin beta subunit promoter and
      TFAP2A expression as factors regulating CGB gene expression in placenta.
AB  - OBJECTIVE: To evaluate mechanisms regulating the expression of CGB genes in
      placental tissues from uncomplicated pregnancies and chorionic samples from
      spontaneous miscarriages. DESIGN: Molecular analyses in human samples. SETTING:
      Laboratory of molecular biology. PATIENT(S): Nine placental samples from term
      deliveries and 21 chorionic samples from miscarriages at 7-13 weeks of gestation.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The expression level of CGBs and
      genes encoding SP1, SP3, and AP2 transcription factors was analyzed using
      quantitative polymerase chain reaction (qPCR). The methylation status of the
      CGBs' promoter regions was determined using methylation-specific PCR. RESULT(S):
      The experiments showed significant differences in CGBs' expression and their
      regulation between placental and chorionic tissues. In placental tissues and
      chorionic tissues from 7 to 9 weeks of gestation, the expression level of CGBs
      was shown to be associated with the amount of TFAP2A transcripts. It was also
      demonstrated that variation in the expression level of CGB genes relies on
      changes in methylation of CGB3-9 and CGB1-2 promoter sequences. CONCLUSION(S):
      During pregnancy, regulation of hCG beta subunit genes expression correlates with
      both methylation of their promoters and TFAP2A expression level. The results
      suggest that these factors may be very influential in the early stages of
      pregnancy and may be associated with pregnancy outcome.

PMID- 25063729
TI  - Determination of regional lung air volume distribution at mid-tidal breathing
      from computed tomography: a retrospective study of normal variability and
      reproducibility.
AB  - BACKGROUND: Determination of regional lung air volume has several clinical
      applications. This study investigates the use of mid-tidal breathing CT scans to
      provide regional lung volume data. METHODS: Low resolution CT scans of the thorax
      were obtained during tidal breathing in 11 healthy control male subjects, each on
      two separate occasions. A 3D map of air volume was derived, and total lung volume
      calculated. The regional distribution of air volume from centre to periphery of
      the lung was analysed using a radial transform and also using one dimensional
      profiles in three orthogonal directions. RESULTS: The total air volumes for the
      right and left lungs were 1035 +/- 280 ml and 864 +/- 315 ml, respectively (mean
      and SD). The corresponding fractional air volume concentrations (FAVC) were 0.680
      +/- 0.044 and 0.658 +/- 0.062. All differences between the right and left lung
      were highly significant (p < 0.0001). The coefficients of variation of repeated
      measurement of right and left lung air volumes and FAVC were 6.5% and 6.9% and
      2.5% and 3.6%, respectively. FAVC correlated significantly with lung space volume
      (r = 0.78) (p < 0.005). FAVC increased from the centre towards the periphery of
      the lung. Central to peripheral ratios were significantly higher for the right
      (0.100 +/- 0.007 SD) than the left (0.089 +/- 0.013 SD) (p < 0.0001). CONCLUSION:
      A technique for measuring the distribution of air volume in the lung at mid-tidal
      breathing is described. Mean values and reproducibility are described for healthy
      male control subjects. Fractional air volume concentration is shown to increase
      with lung size.

PMID- 25063730
TI  - DNA damage signaling regulates age-dependent proliferative capacity of quiescent
      inner ear supporting cells.
AB  - Supporting cells (SCs) of the cochlear (auditory) and vestibular (balance) organs
      hold promise as a platform for therapeutic regeneration of the sensory hair
      cells. Prior data have shown proliferative restrictions of adult SCs forced to re
      enter the cell cycle. By comparing juvenile and adult SCs in explant cultures, we
      have here studied how proliferative restrictions are linked with DNA damage
      signaling. Cyclin D1 overexpression, used to stimulate cell cycle re-entry,
      triggered higher proliferative activity of juvenile SCs. Phosphorylated form of
      histone H2AX (gammaH2AX) and p53 binding protein 1 (53BP1) were induced in a foci
      like pattern in SCs of both ages as an indication of DNA double-strand break
      formation and activated DNA damage response. Compared to juvenile SCs, gammaH2AX
      and the repair protein Rad51 were resolved with slower kinetics in adult SCs,
      accompanied by increased apoptosis. Consistent with thein vitro data, in a Rb
      mutant mouse model in vivo, cell cycle re-entry of SCs was associated with
      gammaH2AX foci induction. In contrast to cell cycle reactivation, pharmacological
      stimulation of SC-to-hair-cell transdifferentiation in vitro did not trigger
      gammaH2AX. Thus, DNA damage and its prolonged resolution are critical barriers in
      the efforts to stimulate proliferation of the adult inner ear SCs. 

PMID- 25063732
TI  - Identification of familial clustering for cancer through the family health
      strategy program in the municipality of Angra dos Reis, Rio de Janeiro, Brazil.
AB  - Identification of families with history of cancer in the municipality of Angra
      dos Reis, Rio de Janeiro (Brazil), through the Brazilian Unified Primary Health
      Care System was explored based in the Community Health Agents (CHA) program. This
      study was divided into two phases: a descriptive one with a cross-sectional
      epidemiological data of families with history of cancer based on CHA-collected
      data from home visits in four primary health care units. The second phase
      consisted in identifying familial clustering of three or more individuals with
      cancer through construction of a three-generation pedigree and revisited by an
      itinerant group of medical geneticists. Genetic counseling was carried out with
      the intent of selecting potential families at risk for hereditary familial
      cancers. In the first phase of the study, 1,581 families were interviewed by the
      CHA at their homes. A positive history for cancer was present in 42.3 % of
      families, comprising 22.3 % with only one case per family, 11.2 % with two cases,
      and 8.6 % with three or more cases in the family. The informant reported that 15
      % of the cases were from the father lineage, 12 % from the mother lineage, and
      12.1 % within siblings. In the remaining 60.9 % families, cancer was present in
      both sides of the family. The types of cancer reported were uterus 8.7 % (n =
      137), stomach 7.7 % (n = 122), breast 6.9 % (n = 109), throat 6.8 % (n = 99),
      prostate 5.4 % (n = 85), lung 5.6 % (n = 88), bowel 3.7 % (n = 59), and
      unspecified sites in 6.8 % (n = 108) of families. No statistical differences were
      noted between the data collected on each primary care unit. In the second phase
      of the study, 136 families (2.9 %) from the total of families interviewed in
      phase 1 were selected due to the presence of three or more individuals with
      cancer in the family. Among those, only 73 families attended genetic counseling.
      Comparison between the data obtained by the CHA and the medical geneticists shows
      complete agreement in 36 cases (49.3 %), partial agreement in 25 cases (34.2 %)
      with more detailed information in the CHA sheets, discordance in 4 cases (5.5 %),
      and not possible to correlate in 8 cases due to identification inconsistency.
      Risk assessment for cancer was calculated based on the criteria adopted by
      Scheuner et al. (Genet Med 12(11):726-735, 2010) and revealed that 50.0 % of the
      families were classified as having a weak risk, 36.1 % a moderate risk, and 13.8
      % were considered of high risk. Concerning known hereditary cancer syndromes, we
      found one family that met the criteria for breast and ovary hereditary cancer
      (1.4 %) and one family with non-polyposis hereditary colon cancer as revised by
      Bethesda protocol. Such preliminary results indicated that the Brazilian Primary
      Health Care system based on the CHA framework can be an effective entrance into
      the Unified Brazilian Health Care System (SUS-Brazil) for individuals with
      genetically determined diseases, such as familial cancer. Families with a history
      of three or more cases of cancer and considered of high risk for familial cancer
      could be referred to a tertiary health center for proper oncogenetic counseling. 

PMID- 25063731
TI  - Gamma band activity and the P3 reflect post-perceptual processes, not visual
      awareness.
AB  - A primary goal in cognitive neuroscience is to identify neural correlates of
      conscious perception (NCC). By contrasting conditions in which subjects are aware
      versus unaware of identical visual stimuli, a number of candidate NCCs have
      emerged; among them are induced gamma band activity in the EEG and the P3 event
      related potential. In most previous studies, however, the critical stimuli were
      always directly relevant to the subjects' task, such that aware versus unaware
      contrasts may well have included differences in post-perceptual processing in
      addition to differences in conscious perception per se. Here, in a series of EEG
      experiments, visual awareness and task relevance were manipulated independently.
      Induced gamma activity and the P3 were absent for task-irrelevant stimuli
      regardless of whether subjects were aware of such stimuli. For task-relevant
      stimuli, gamma and the P3 were robust and dissociable, indicating that each
      reflects distinct post-perceptual processes necessary for carrying-out the task
      but not for consciously perceiving the stimuli. Overall, this pattern of results
      challenges a number of previous proposals linking gamma band activity and the P3
      to conscious perception. 

PMID- 25063733
TI  - Single nucleotide polymorphism-single nucleotide polymorphism interactions among
      inflammation genes in the genetic architecture of blood pressure in the
      Framingham Heart Study.
AB  - BACKGROUND: Hypertension is a major global health burden, but, although systolic
      and diastolic blood pressure (BP) each have estimated heritability of at least
      30%, <3% of their variance has been attributed to particular genetic variants.
      Few studies have shown interactions between pairs of single nucleotide
      polymorphisms (SNPs) to be associated with BP. Although many studies use a
      Bonferroni correction for multiple testing to control type I error, thereby
      potentially reducing power, false discovery rate (FDR) approaches are also used
      in genome-wide studies. Renal ion balance genes have been associated with BP
      regulation, but, although inflammation has been studied in connection with BP,
      few studies have reported associations between inflammation genes and BP.
      METHODS: We analyzed SNP-SNP interactions among 31 SNPs from genes involved in
      renal ion balance and 30 SNPs from genes involved in inflammation using data from
      the Framingham Heart Study. RESULTS: No evidence of association was found for
      interactions among renal ion balance SNPs for either systolic or diastolic BP. A
      group of 3 interactions involving 6 inflammation genes (IKBKB-NFKBIA, IKBKE-CHUK,
      and ADIPOR2-RETN) showed evidence of association with diastolic BP with an FDR of
      4.2%; no single interaction reached experiment-wide significance. CONCLUSIONS:
      This study identified promising and biologically plausible candidates for
      interactions between inflammation genes that may be associated with DBP. Analysis
      using the FDR may allow detection of signals in the presence of modest noise
      (false positives) that a stringent approach based on Bonferroni-corrected P value
      thresholds may miss.

PMID- 25063734
TI  - Prevalence, awareness, treatment and control of hypertension in Macau: results
      from a cross-sectional epidemiological study in Macau, China.
AB  - BACKGROUND: Awareness of hypertension, as well as its prevalence, treatment, and
      control status, has not been comprehensively investigated in Macau Special
      Administrative Region (SAR), China. METHODS: A survey was conducted on a randomly
      sampled population of 1,410 participants (n = 638 men) aged 18-93 years in 2012.
      Blood pressure was individually measured twice. Awareness, treatment, and control
      of hypertension were assessed by interview-administered questionnaire. RESULTS:
      Prevalence of hypertension was 34% in Macau, similar to the United States (30%)
      and United Kingdom (31%). Among hypertensives, 69% were aware of their condition,
      59% were treated, and 30% were adequately controlled. Older age (>=50 years; odds
      ratio (OR) = 5.3; 95% confidence interval (CI) = 4.6-6.1), being of the male sex
      (OR = 2.2; 95% CI = 1.9-2.5), having retired (OR = 2.0; 95% CI = 1.8-2.3), being
      married (OR = 1.5; 95% CI = 1.3-1.9), having a low level of education in women
      (OR = 1.5; 95% CI = 1.1-2.1), Pinteraction = 0.01), and lack of salt awareness
      (OR = 1.1; 95% CI = 1.0-1.3) were associated with hypertension. Older age, having
      retired, and being married were also associated with higher awareness and
      treatment rates. Those who were older and married were better controlled. These
      demographic factors differed by sex. Those who had some knowledge of salt intake
      were more likely to have higher hypertension awareness, treatment, and control
      rates. CONCLUSIONS: The prevalence of hypertension in Macau in 2012 has increased
      compared with 2006 (28%) and is comparable with prevalence rates in developed
      countries. Specific health promotion campaigns related to knowledge of risk
      factors such as salt intake and smoking may be useful for hypertension prevention
      and to improve hypertension awareness, treatment, and control rates.

PMID- 25063735
TI  - Predictors of silent myocardial ischemia in resistant hypertensive patients.
AB  - BACKGROUND: Hypertension is the most prevalent and significant modifiable risk
      factor for coronary heart disease. A portion of patients with uncontrolled
      hypertension are considered to have resistant hypertension (RHTN). Myocardial
      ischemia incidence increases along with blood pressure (BP) levels. However, the
      prevalence of myocardial ischemia in patients with RHTN, as well as the factors
      associated with it, is unknown. METHODS: We enrolled 129 patients with true RHTN
      regularly followed in our specialty hypertension clinic and evaluated then by
      resting and dipyridamole pharmacological stress myocardial perfusion
      scintigraphy. Patients were then divided into 2 groups: those with (I-RHTN; n =
      36) and those without (NI-RHTN; n = 93) myocardial ischemia. Echocardiography, 24
      hour ambulatory BP monitoring (ABPM), and flow mediated dilation (FMD) were also
      evaluated. RESULTS: Thirty six (28%) patients had myocardial ischemia. There was
      no difference between groups regarding age, sex, biochemical parameters, office,
      and 24-hour ABPM levels. Patients in the I-RHTN group were more likely diabetic
      (31% vs. 11%; P < 0.05) and obese (75% vs. 40%; P < 0.001). Adjusting for age and
      body mass index, multiple logistic regression showed that diabetes (odds ratio
      (OR) = 6.5; 95% confidence interval (CI) = 1.06-40.14; P = 0.04), FMD (OR = 0.18;
      95% CI = 0.07-0.41; P < 0.001), heart rate (OR = 1.23; 95% CI = 1.11-1.36; P <
      0.001), left ventricular mass index (OR = 1.02; 95% CI = 1.01-1.04; P = 0.04),
      and microalbuminuria (OR = 1.02; 95% CI = 1.01-1.04; P = 0.002) were independent
      predictors of ischemia. CONCLUSIONS: In conclusion, there is a high prevalence of
      myocardial ischemia in patients with RHTN. Increased microalbuminuria, heart
      rate, endothelial dysfunction, and left ventricular mass can be useful to guide
      the investigation for myocardial ischemia in these high risk patients.

PMID- 25063736
TI  - Enhanced needle localization in ultrasound using beam steering and learning-based
      segmentation.
AB  - Segmentation of needles in ultrasound images remains a challenging problem. In
      this paper, we introduce a machine learning-based method for needle segmentation
      in 2D beam-steered ultrasound images. We used a statistical boosting approach to
      train a pixel-wise classifier for needle segmentation. The Radon transform was
      then used to find the needle position and orientation from the segmented image.
      We validated our method with data from ex vivo specimens and clinical nerve block
      procedures, and compared the results to those obtained using previously reported
      needle segmentation methods. Results show improved localization success and
      accuracy using the proposed method. For the ex vivo datasets, assuming that the
      needle orientation was known a priori, the needle was successfully localized in
      86.2% of the images, with a mean targeting error of 0.48mm. The robustness of the
      proposed method to a lack of a priori knowledge of needle orientation was also
      demonstrated. For the clinical datasets, assuming that the needle orientation was
      closely aligned with the beam steering angle selected by the physician, the
      needle was successfully localized in 99.8% of the images, with a mean targeting
      error 0.19mm. These results indicate that the learning-based segmentation method
      may allow for increased targeting accuracy and enhanced visualization during
      ultrasound-guided needle procedures. 

PMID- 25063737
TI  - SIRT1 in cardiovascular aging.
AB  - Cardiovascular disease (CVD) is the leading cause of death worldwide, with aging
      as the key independent risk factor. Effective interventions are necessary to
      delay aging. Sirtuin1 (SIRT1), a NAD(+)-dependent histone deacetylase, is closely
      related to lifespan extension. SIRT1 exerts beneficial effects on aging and age
      related diseases, such as atherosclerosis. In this review, we summarize the
      current knowledge on the functions of SIRT1 in cardiovascular aging, focusing on
      the underlying molecular mechanisms, including inhibition of oxidative stress and
      inflammation, and induction of autophagy. We also demonstrate that moderate up
      regulation or activation of SIRT1 in cardiovascular aging and age-related CVD may
      confer important application values. 

PMID- 25063739
TI  - MicroRNA-370 suppresses proliferation and promotes endometrioid ovarian cancer
      chemosensitivity to cDDP by negatively regulating ENG.
AB  - MicroRNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally
      inhibit gene expression. In this study, we discovered that microRNA-370 (miR-370)
      was down-regulated in endometrioid ovarian cancer cells. In IGROV1 and TOV112D
      endometrioid ovarian cancer cells, miR-370 suppressed cellular viability and
      colony formation. miR-370 also enhanced endometrioid ovarian cancer cell
      chemosensitivity to cDDP. Endoglin (ENG) was directly and negatively regulated by
      miR-370. In addition, hypermethylation was a potential mechanism of miR-370
      epigenetic silencing. We conclude that miR-370 acts as a tumor suppressor in
      endometrioid ovarian cancer via ENG regulation. 

PMID- 25063738
TI  - Epigenetic silencing of microRNA-373 to epithelial-mesenchymal transition in non
      small cell lung cancer through IRAK2 and LAMP1 axes.
AB  - The role of microRNAs (miRNAs) in carcinogenesis as tumor suppressors or
      oncogenes has been widely reported. Epigenetic change is one of the mechanisms of
      transcriptional silencing of miRNAs in cancer. To identify lung cancer-related
      miRNAs that are mediated by histone modification, we conducted microarray
      analysis in the Calu-6 non-small cell lung cancer (NSCLC) cell line after
      treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase
      (HDAC) inhibitor. The expression level of miR-373 was enhanced by SAHA treatment
      in this cell line by microarray and the following quantitative RT-PCR analyses.
      Treatment with another HDAC inhibitor, Trichostatin A, restored the levels of miR
      373 expression in A549 and Calu-6 cells, while demethylation drug treatment did
      not. Importantly, miR-373 was found to be down-regulated in NSCLC tissues and
      cell lines. Transfection of miR-373 into A549 and Calu-6 cells attenuated cell
      proliferation, migration, and invasion and reduced the expression of mesenchymal
      markers. Additional microarray analysis of miR-373-transfected cells and
      computational predictions identified IRAK2 and LAMP1 as targets of miR-373.
      Knockdown of these two genes showed similar biological effects to those of miR
      373 overexpression. In clinical samples, overexpression of IRAK2 correlated with
      decreased disease-free survival of patients with non-adenocarcinoma. In
      conclusion, we found that miR-373 is silenced by histone modification in lung
      cancer cells and identified its function as a tumor suppressor and negative
      regulator of the mesenchymal phenotype through downstream IRAK2 and LAMP1 target
      genes. 

PMID- 25063740
TI  - Helicobacter pylori infection and the risk of acute coronary syndrome: a
      nationwide retrospective cohort study.
AB  - Helicobacter pylori infection (HPI) imposes substantial social costs and is of
      major etiological importance in peptic ulcer disease, gastric cancer, and
      accelerated cardiovascular diseases. This study determined the risk of acute
      coronary syndrome (ACS) associated with HPI in a nationwide retrospective cohort
      study. By using the Taiwan National Health Insurance Research Database (NHIRD),
      we identified patients diagnosed with HPI from 1998 to 2010. In addition, we
      randomly selected non-HPI controls frequency-matched by age, sex, and index year
      from the general population free of HPI. The risk of ACS was analyzed using Cox
      proportional hazards regression models in which sex, age, and comorbidities were
      included as variables. We identified 17,075 participants for the HPI group and
      selected 68,300 participants for the comparison group. The incidence rates were
      increased in the patients in the HPI group compared with those in the comparison
      group. Overall, the HPI patients exhibited a 1.93-fold high crude hazard ratio
      for ACS, and a 1.48-fold adjusted hazard ratio after age, sex, and comorbidities
      were adjusted. However, the overall adjusted hazard ratio of ACS increased with
      increasing age with a 3.11 to 8.24 adjusted hazard ratio among the various age
      groups. Several comorbidities, such as diabetes, hyperlipidemia, and COPD
      exhibited synergistic effects for ACS risk. We determined a significant
      association between ACS and comorbidities and provide evidence to encourage
      clinicians to observe ACS-related comorbidities. 

PMID- 25063741
TI  - Placental alpha-microglobulin-1 and combined traditional diagnostic test: a cost
      benefit analysis.
AB  - OBJECTIVE: We sought to evaluate if the placental alpha-microglobulin (PAMG)-1
      test vs the combined traditional diagnostic test (CTDT) of pooling, nitrazine,
      and ferning would be a cost-beneficial screening strategy in the setting of
      potential preterm premature rupture of membranes. STUDY DESIGN: A decision
      analysis model was used to estimate the economic impact of PAMG-1 test vs the
      CTDT on preterm delivery costs from a societal perspective. Our primary outcome
      was the annual net cost-benefit per person tested. Baseline probabilities and
      costs assumptions were derived from published literature. We conducted
      sensitivity analyses using both deterministic and probabilistic models. Cost
      estimates reflect 2013 US dollars. RESULTS: Annual net benefit from PAMG-1 was
      $20,014 per person tested, while CTDT had a net benefit of $15,757 per person
      tested. If the probability of rupture is <38%, PAMG-1 will be cost-beneficial
      with an annual net benefit of $16,000-37,000 per person tested, while CTDT will
      have an annual net benefit of $16,000-19,500 per person tested. If the
      probability of rupture is >38%, CTDT is more cost-beneficial. Monte Carlo
      simulations of 1 million trials selected PAMG-1 as the optimal strategy with a
      frequency of 89%, while CTDT was only selected as the optimal strategy with a
      frequency of 11%. Sensitivity analyses were robust. CONCLUSION: Our cost-benefit
      analysis provides the economic evidence for the adoption of PAMG-1 in diagnosing
      preterm premature rupture of membranes in uncertain presentations and when CTDT
      is equivocal at 34 to <37 weeks' gestation.

PMID- 25063742
TI  - Why should I review journal manuscripts?

PMID- 25063743
TI  - The view from the other side.

PMID- 25063744
TI  - Platelet-rich plasma in orthopaedic applications: evidence-based recommendations
      for treatment.

PMID- 25063745
TI  - The use of arthrography in pediatric orthopaedic surgery.
AB  - Surgery near pediatric joints can be challenging because it is difficult to
      visualize vital articular structures. Assessment of underlying pathology is also
      challenging because the joint structures have not yet ossified. Arthrography is a
      useful tool that is quick and minimally invasive and allows adequate
      visualization of joint anatomy during surgery, which aids intraoperative decision
      making. In pediatric patients, arthrography is most useful for visualization of
      the elbow, knee, and hip joints. This tool can help the surgeon to refine the
      diagnosis and management of pediatric fractures and aids in surgical assessment
      during joint and limb reconstruction. Arthrography adds minimal time to surgery
      and carries a low risk of complications; it should be part of the armamentarium
      of any surgeon who treats pediatric orthopaedic patients. 

PMID- 25063746
TI  - Periprosthetic fractures around loose femoral components.
AB  - The development of periprosthetic fractures around loose femoral components can
      be a devastating event for patients who have undergone total hip arthroplasty
      (THA). As indications for THA expand in an aging population and to use in younger
      patients, these fractures are increasing in incidence. This review covers the
      epidemiology, risk factors, prevention, and clinical management of periprosthetic
      femoral fractures. Treatment principles and reconstructive options are discussed,
      along with outcomes and complications. Femoral revision with a long-stem
      prosthesis or a modular tapered stem is the mainstay of treatment and has
      demonstrated good outcomes in the literature. Other reconstruction options are
      available, depending on bone quality. Surgeons must have a sound understanding of
      the diagnosis and treatment of periprosthetic femoral fractures. 

PMID- 25063747
TI  - Management of malunion of the proximal humerus: current concepts.
AB  - Proximal humerus fractures remain one of the most common orthopaedic injuries,
      particularly in the elderly. Displaced fractures often require surgery, and
      management can be challenging because of comminution and poor bone quality.
      Despite advances in surgical technique and implant design, reoperation for
      malunion or nonunion of the tuberosity (arthroplasty) or screw penetration (open
      reduction and internal fixation) remains problematic. Recent studies have
      demonstrated acceptable results following nonsurgical management of displaced
      proximal humerus fractures in elderly, low-demand patients. In younger, more
      active patients, reduced function and pain that accompany select proximal humeral
      malunions are generally poorly tolerated. Surgical options for symptomatic,
      malunited tuberosities include osteotomy, tuberoplasty with rotator cuff repair
      and subacromial decompression, or decompression alone. Surgical neck malunion can
      be managed with corrective osteotomy and preservation of the native joint.
      Arthroplasty is reserved for complex malunions with joint incongruity. Surgical
      management of symptomatic proximal humeral malunion remains challenging, but good
      outcomes can be achieved with proper patient selection. 

PMID- 25063748
TI  - Posterior lumbar fusion: choice of approach and adjunct techniques.
AB  - The choice among the many options of approach and adjunct techniques in planning
      a posterior lumbar fusion can be problematic. Debates remain as to whether solid
      fusion has an advantage over pseudarthrosis regarding long-term symptom
      deterioration and whether an instrumented or a noninstrumented approach will best
      serve clinically and/or cost effectively, particularly in elderly patients.
      Increased motion resulting in higher rates of nonunion and the use of
      nonsteroidal anti-inflammatory drugs have been studied in animal models and are
      presumed risk factors, despite the lack of clinical investigation. Smoking is a
      proven risk factor for pseudarthrosis in both animal models and level III
      clinical studies. Recent long-term studies and image/clinical assessment of
      lumbar fusions and pseudarthrosis show that, although imaging remains a key area
      of difficulty in assessment, including an instrumented approach and a well
      selected biologic adjunct, as well as achieving a solid fusion, all carry
      important long-term clinical advantages in avoiding revision surgery for
      nonunion. 

PMID- 25063749
TI  - Subtle cavus foot: diagnosis and management.
AB  - The subtle cavovarus foot (SCF) is a mild malalignment caused by either primary
      hindfoot varus or a plantarflexed first ray, resulting in a typical constellation
      of symptoms because of altered foot mechanics. Key clinical signs are a peek-a
      boo heel and a positive Coleman block test. The cavovarus position places lateral
      ankle soft-tissue structures, such as the anterior talofibular ligament and the
      peroneal tendons, on stretch during normal gait. This can lead to common
      conditions such as lateral ankle instability, peroneal tendon tears, and stress
      fractures of the lateral metatarsals and cuboid. The gait cycle is altered
      because a greater proportion of time is spent with the transverse tarsal joints
      locked due to the overall varus foot position. In contradistinction to
      physiologic valgus at heel strike, which maintains the transverse tarsal joints
      unlocked and affords approximately 50% force dissipation, the increased rigidity
      of the foot causes a maldistribution of forces that leads to accelerated wear of
      the midfoot joints and increased stresses along the plantar fascia and the
      Achilles tendon insertion. Successful nonsurgical management requires correction
      of the biomechanical anomaly; surgical management of a subtle cavovarus foot
      typically is part of a comprehensive plan for correcting the symptoms and the
      malalignment. 

PMID- 25063750
TI  - Posterosuperior rotator cuff tears: classification, pattern recognition, and
      treatment.
AB  - The posterosuperior rotator cuff, composed of the supraspinatus and infraspinatus
      tendons, is the most common site for full-thickness rotator cuff tears and
      represents a significant source of shoulder disability worldwide. Recognition of
      and classification of full-thickness tear patterns are essential in order to
      optimize surgical treatment and to improve prognosis. Until recently, tear
      patterns have been described using one- or two-dimensional classification
      systems. Three-dimensional pattern recognition is critical to achieving the most
      successful outcome possible. For more complex patterns, a combination of side-to
      side stitching, margin convergence, and interval slide techniques may be needed
      to achieve a tension-free tendon-bone repair. Biomechanical and anatomic evidence
      supports the use of linked double-row repairs for most full-thickness tears.
      Although double-row repairs seem to result in improved structural outcomes,
      clinical evidence has not shown differences in outcomes scores between single-row
      and double-row repairs. Single-row repair may be performed in partial-thickness,
      small full-thickness, or very massive, immobile tears, whereas double-row repair
      may be performed in most other cases. 

PMID- 25063751
TI  - Psychiatric morbidity and predisposing factors in a primary care population in
      Madrid.
AB  - OBJECTIVES: The aim of this article is to estimate the prevalence of mental
      disorders in patients in primary care centers in an urban area of Madrid and to
      study possible associated risk factors. METHODS: Cross-sectional month prevalence
      was evaluated in two phases in an urban area of Madrid. The sample for the first
      phase included 635 individuals (aged 18-65 years), and the second phase included
      320 individuals. Socio-demographic variables (age, sex, educational level, living
      conditions and country of origin) and clinical variables (psychiatric diagnosis
      and level of psychosocial stress) were studied. The instruments used for
      screening were the General Health Questionnaire (GHQ)-28 item questionnaire and
      the MULTICAGE-CAD 4test. The Mini International Neuropsychiatric Interview
      (M.I.N.I.) was used in the second phase (in 'possible cases' and 20% of the 'non
      cases'). Prevalence was calculated using weighted logistic regression with the
      observed sampling fractions of the patients in study phase 2 as sample weights.
      RESULTS AND CONCLUSIONS: The month prevalence of mental disorders was 31.3% (95%
      confidence interval (CI) = [27.6, 35.2]). Anxiety disorders were the most
      frequent diagnoses with a prevalence of 22.4% (95% CI = [17.8, 27.1]), followed
      by depressive disorders (16.6%; 95% CI = [12.9, 20.3]), substance abuse or
      dependence disorders (5.6%; 95% CI = [3.2, 6.9]) and posttraumatic stress
      disorder (PTSD; 4.4%; 95% CI = [2.0, 2.8]). Factors associated with mental
      disorders were the presence of stressful life events in the previous 12 months,
      Latin American region of origin, being woman aged 25 and 34 years and having a
      low education level.

PMID- 25063752
TI  - The prevalence and correlates of severe social withdrawal (hikikomori) in Hong
      Kong: A cross-sectional telephone-based survey study.
AB  - BACKGROUND: Severe social withdrawal behaviors among young people have been a
      subject of public and clinical concerns. AIMS: This study aimed to explore the
      prevalence of social withdrawal behaviors among young people aged 12-29 years in
      Hong Kong. METHODS: A cross-sectional telephone-based survey was conducted with
      1,010 young individuals. Social withdrawal behaviors were measured with the
      proposed research diagnostic criteria for hikikomori and were categorized
      according to the (a) international proposed duration criterion (more than 6
      months), (b) local proposed criterion (less than 6 months) and (c) with
      withdrawal behaviors but self-perceived as non-problematic. The correlates of
      social withdrawal among the three groups were examined using multinomial and
      ordinal logistic regression analyses. RESULTS: The prevalence rates of more than
      6 months, less than 6 months and self-perceived non-problematic social withdrawal
      were 1.9%, 2.5% and 2.6%, respectively. In terms of the correlates, the
      internationally and locally defined socially withdrawn youths are similar, while
      the self-perceived non-problematic group is comparable to the comparison group.
      CONCLUSIONS: The study finds that the prevalence of severe social withdrawal in
      Hong Kong is comparable to that in Japan. Both groups with withdrawal behaviors
      for more or less than 6 months share similar characteristics and are related to
      other contemporary youth issues, for example, compensated dating and self-injury
      behavior. The self-perceived non-problematic group appears to be a distinct group
      and the withdrawal behaviors of its members may be discretionary.

PMID- 25063753
TI  - The dynamic exome: acquired variants as individuals age.
AB  - A singular genome used for inference into population-based studies is a standard
      method in genomics. Recent studies show that spontaneous genomic variants can
      propagate into new generations and these changes can contribute to individual
      cell aging with environmental and evolutionary elements contributing to
      cumulative genomic variation. However, the contribution of aging to genomic
      changes in tissue samples remains uncharacterized. Here, we report the impact of
      aging on individual human exomes and their implications. We found the human
      genome to be dynamic, acquiring a varying number of mutations with age (5,000 to
      50,000 in 9 to 16 years). This equates to a variation rate of 9.6x10(-7) to
      8.4x10(-6) bp(-1) year(-1) for nonsynonymous single nucleotide variants and
      2.0x10(-4) to 1.0x10(-3) locus(-1) year(-1) for microsatellite loci in these
      individuals. These mutations span across 3,000 to 13,000 genes, which commonly
      showed association with Wnt signaling and Gonadotropin releasing hormone receptor
      pathways, and indicated for individuals a specific and significant enrichment for
      increased risk for diabetes, kidney failure, cancer, Rheumatoid arthritis, and
      Alzheimer's disease--conditions usually associated with aging. The results
      suggest that "age" is an important variable while analyzing an individual human
      genome to extract individual-specific clinically significant information
      necessary for personalized genomics.

PMID- 25063754
TI  - 20 years of leptin: insights into signaling assemblies of the leptin receptor.
AB  - Leptin plays a central role in the control of body weight and energy homeostasis,
      but is a pleiotropic cytokine with activities on many peripheral cell types. In
      this review, we discuss the interaction of leptin with its receptor, and focus on
      the structural and mechanistic aspects of the extracellular aspects of leptin
      receptor (LR) activation. We provide an extensive overview of all structural
      information that has been obtained for leptin and its receptor via X-ray
      crystallography, electron microscopy, small-angle X-ray scattering, homology
      modeling, and mutagenesis studies. The available knowledge is integrated into
      putative models toward a recapitulation of the LR activation mechanism. 

PMID- 25063756
TI  - Prolactin receptor antagonism uncouples lipids from atherosclerosis
      susceptibility.
AB  - The pituitary-derived hormone prolactin has been suggested to stimulate the
      development of atherosclerosis and cardiovascular disease through its effects on
      metabolism and inflammation. In this study, we aimed to challenge the hypothesis
      that inhibition of prolactin function may beneficially affect atherosclerosis
      burden. Hereto, atherosclerosis-susceptible LDL receptor (Ldlr) knockout mice
      were transplanted with bone marrow from transgenic mice expressing the pure
      prolactin receptor antagonist Del1-9-G129R-hPRL or their non-transgenic
      littermates as control. Recipient mice expressing Del1-9-G129R-hPRL exhibited a
      decrease in plasma cholesterol levels (-29%; P<0.05) upon feeding a Western-type
      diet (WTD), which could be attributed to a marked decrease (-47%; P<0.01) in the
      amount of cholesterol esters associated with pro-atherogenic lipoproteins
      VLDL/LDL. By contrast, Del1-9-G129R-hPRL-expressing mice did not display any
      change in the susceptibility for atherosclerosis after 12 weeks of WTD feeding.
      Both the absolute atherosclerotic lesion size (223 +/- 33 * 10(3) MUm(2) for Del1
      9-G129R-hPRL vs 259 +/- 32 * 10(3) MUm(2) for controls) and the lesional
      macrophage and collagen contents were not different between the two groups of
      bone marrow recipients. Importantly, Del1-9-G129R-hPRL exposure increased levels
      of circulating neutrophils (+91%; P<0.05), lymphocytes (+55%; P<0.05), and
      monocytes (+43%; P<0.05), resulting in a 49% higher (P<0.01) total blood
      leukocyte count. In conclusion, we have shown that prolactin receptor signaling
      inhibition uncouples the plasma atherogenic index from atherosclerosis
      susceptibility in Ldlr knockout mice. Despite an associated decrease in VLDL/LDL
      cholesterol levels, application of the prolactin receptor antagonist Del1-9-G129R
      hPRL does not alter the susceptibility for initial development of atherosclerotic
      lesions probably due to the parallel increase in circulating leukocyte
      concentrations.

PMID- 25063755
TI  - 20 years of leptin: role of leptin in energy homeostasis in humans.
AB  - The hyperphagia, low sympathetic nervous system tone, and decreased circulating
      concentrations of bioactive thyroid hormones that are common to states of
      congenital leptin deficiency and hypoleptinemia following and during weight loss
      suggest that the major physiological function of leptin is to signal states of
      negative energy balance and decreased energy stores. In weight-reduced humans,
      these phenotypes together with pronounced hypometabolism and increased
      parasympathetic nervous system tone create the optimal circumstance for weight
      regain. Based on the weight loss induced by leptin administration in states of
      leptin deficiency (obese) and observed similarity of phenotypes in states of
      congenital and dietary-induced states of hypoleptinemia (reduced obese), it has
      been suggested that exogenous leptin could potentially be useful in initiating,
      promoting, and sustaining weight reduction. However, the responses of human
      beings to exogenous leptin administration are dependent not only on extant energy
      stores but also on energy balance. Leptin administration to humans at usual
      weight has little, if any, effect on body weight while leptin administration
      during weight loss mitigates hunger, especially if given in supraphysiological
      doses during severe caloric restriction. Leptin repletion is most effective
      following weight loss by dietary restriction. In this state of weight stability
      but reduced energy stores, leptin at least partially reverses many of the
      metabolic, autonomic, neuroendocrine, and behavioral adaptations that favor
      weight regain. The major physiological function of leptin is to signal states of
      negative energy balance and decreased energy stores. Leptin, and
      pharmacotherapies affecting leptin signaling pathways, is likely to be most
      useful in sustaining weight loss. 

PMID- 25063757
TI  - Altered VEGF-stimulated Ca2+ signaling in part underlies pregnancy-adapted eNOS
      activity in UAEC.
AB  - In pregnancy, the uterine vasculature undergoes dramatic vasodilatory
      adaptations. Previously, vascular endothelial growth factor (VEGF) has been shown
      to stimulate endothelial nitric oxide synthase (eNOS) in uterine artery
      endothelial cells (UAECs) derived from pregnant ewes to a greater extent than
      those from non-pregnant ewes in a manner not fully explained by changes in the
      phosphorylation of eNOS. In this study, we used Fura-2 Ca(2+) imaging and
      arginine-to-citrulline conversion eNOS activity assays to assess the importance
      of VEGF-stimulated Ca(2+) responses in pregnancy-related changes in NO production
      in UAEC. In this study, we show that pregnancy-induced changes in VEGF-stimulated
      Ca(2+) responses could account in part for the greater capacity of VEGF to
      stimulate eNOS in UAECs from pregnant versus non-pregnant animals. VEGF
      stimulated Ca(2+) responses in UAECs from pregnant and non-pregnant animals were
      mediated through VEGF receptor 2 and were detected in roughly 15% of all cells.
      There were no pregnancy-specific differences in area under the curve or peak
      height. UAECs from pregnant animals were more consistent in the time to response
      initiation, had a larger component of extracellular Ca(2+) entry, and were more
      sensitive to a submaximal dose of VEGF. In UAECs from pregnant and non-pregnant
      animals Ca(2+) responses and eNOS activation were sensitive to the phospholipase
      C/inositol 1,4,5-trisphosphate pathway inhibitors 2-aminoethoxydiphenylborane and
      U73122. Thus, changes in VEGF-stimulated [Ca(2+)]i are necessary for eNOS
      activation in UAECs, and pregnancy-induced changes in Ca(2+) responses could also
      in part explain the pregnancy-specific adaptive increase in eNOS activity in
      UAECs. 

PMID- 25063758
TI  - The Cushing response evoked by a fourth ventricular brainstem mass.

PMID- 25063760
TI  - Genomics in clinical practice.

PMID- 25063759
TI  - Posterior white matter disease distribution as a predictor of amyloid angiopathy.
AB  - OBJECTIVES: We sought to examine whether a posterior distribution of white matter
      hyperintensities (WMH) is an independent predictor of pathologically confirmed
      cerebral amyloid angiopathy (CAA) and whether it is associated with MRI markers
      of CAA, in patients without lobar intracerebral hemorrhage. METHODS: We developed
      a quantitative method to measure anteroposterior (AP) distribution of WMH. A
      retrospective cohort of patients without intracerebral hemorrhage and with
      pathologic evaluation of CAA was examined to determine whether posterior WMH
      distribution was an independent predictor of CAA (n=59). The relationship of AP
      distributions of WMH to strictly lobar microbleeds (MBs) (n=259) and location of
      dilated perivascular spaces (DPVS) (n=85) was examined in a separate cohort of
      patients evaluated in a memory clinic. RESULTS: A more posterior WMH distribution
      was found to be an independent predictor of pathologic evidence of CAA (p=0.001,
      odds ratio [95% confidence interval]=1.19 [1.07-1.32]), even in the subgroup
      without lobar MBs (p=0.016, odds ratio [95% confidence interval]=1.18 [1.03
      1.36]). In the memory clinic cohort, strictly lobar MBs were independently
      associated with more posterior WMH distribution (p=0.009). AP distribution of WMH
      was also associated with location of DPVS (p=0.001), in that patients with
      predominant DPVS in the white matter over the basal ganglia harbored a more
      posterior WMH distribution. CONCLUSIONS: Our results suggest that AP distribution
      of WMH may represent an additional marker of CAA, irrespective of the presence of
      lobar hemorrhages. CLASSIFICATION OF EVIDENCE: This study provides Class III
      evidence that there is a significant association between the AP distribution of
      WMH on MRI with the presence of pathologically confirmed CAA pathology.

PMID- 25063761
TI  - Choroid plexus papilloma-A case highlighting the challenges of extrapolating
      pediatric chemotherapy regimens to adult populations.
AB  - The treatment of adults who present with rare pediatric tumors is not
      characterized well in the literature. We report an instance of a 40-year-old
      African American woman with a diagnosis of choroid plexus carcinoma admitted to
      the intensive care unit for severe sepsis seven days after receiving chemotherapy
      consisting of carboplatin (350 mg/m(2) on Days 1 and 2 plus etoposide 100 mg/m(2)
      on Days 1-5). Her laboratory results were significant for an absolute neutrophil
      count of 0/uL and blood cultures positive for Capnocytophagia species. She was
      supported with broad spectrum antibiotics and myeloid growth factors. She
      eventually recovered and was discharged in stable condition. The management of
      adults with malignancies most commonly seen in pediatric populations presents
      substantial challenges. There are multiple age-specific differences in renal and
      hepatic function that explain the need for higher dosing in pediatric patients
      without increasing the risk of toxicity. Furthermore, differences in
      pharmacokinetic parameters such as absorption, distribution, and clearance are
      present but are less likely to affect patients. It is expected that the pediatric
      population will have more bone marrow reserve and, therefore, less susceptible to
      myelosuppression. The extrapolation of pediatric dosing to an adult presents a
      problematic situation in treating adults with malignancies that primarily effect
      pediatric patients. We recommend extrapolating from adult treatment regimens with
      similar agents rather than extrapolating from pediatric treatment regimens to
      reduce the risk of toxicity. We also recommend the consideration of adding
      myeloid growth factors. If the treatment is tolerated without significant
      toxicity, dose escalation can be considered.

PMID- 25063762
TI  - Acute jugular vein thrombosis during rituximab administration: Review of the
      literature.
AB  - Rituximab, a chimeric monoclonal antibody is licensed for the treatment of CD20
      positive lymphomas. Previous studies have found rituximab, in combination with
      cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, is
      superior to cyclophosphamide, doxorubicin, vincristine, and prednisone alone in
      the treatment of diffuse large B-cell lymphoma and many other B-cell lymphomas.
      Acute hypersensitivity reactions have been reported in patients receiving
      rituximab infusion and usually manifesting as headache, fever, chills, sweats,
      skin rash, dyspnea, mild hypotension, and nausea. Acute major venous thrombosis
      and seizures have not been reported as manifestation of acute hypersensitivity
      reaction. We report on a 22-year-old woman, who was diagnosed with stage III B
      CD20 positive B-cell diffuse large B-cell lymphoma. During the first cycle of
      treatment, she developed grand-mal seizure while receiving rituximab infusion
      without any other features of acute hypersensitivity reaction. Imaging confirmed
      new onset jugular vein thrombosis with normal coagulation parameters. These
      events were managed by anticonvulsants and anticoagulation therapy. The patient
      completed eight cycles of cyclophosphamide, doxorubicin, vincristine, and
      prednisone without rituximab and achieved complete remission. No further
      complications were noted. To our knowledge, this is the first case in the
      literature describing grand-mal seizures and acute thrombosis while on rituximab
      treatment. Clinicians should be aware of this rare side effect, as stopping
      rituximab can prevent recurrence of these complications. 

PMID- 25063763
TI  - Successful treatment of severe thrombocytopenia with the use of thrombopoeitin
      receptor agonist eltrombopag in a patient with chronic myelomonocytic leukemia.
AB  - Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoietic stem
      cells often occurring in elderly patients. The combination of CMML with
      autoimmune manifestations, including immune-mediated thrombocytopenia, has been
      described before in a number of case reports. To our knowledge, this is the first
      reported case of the successful treatment of CMML-related thrombocytopenia with a
      thrombopoeitin receptor agonist, eltrombopag. 

PMID- 25063764
TI  - Platelet Reactivity in Patients With Stroke and Hyperlipidemia, GPIbalpha
      Assessment.
AB  - The aim of this study was to assess platelet reactivity in patients after
      ischemic stroke and to investigate the influence of hyperlipidemia (HL) on
      platelet activity markers. A total of 41 patients after ischemic stroke were
      divided into the following 2 groups: patients with HL and patients with
      normolipidemia. Expression of CD42b on resting, thrombin-activated blood
      platelets, and fibrinogen level was assessed. The CD42b-positive platelets were
      analyzed using the flow cytometer, anti-CD61, and anti-CD42b monoclonal
      antibodies. The results confirmed increased platelet reactivity to thrombin in
      all patients after ischemic stroke manifested by significantly lower CD42b
      expression and percentage of CD42b(+) platelets after activation by thrombin. The
      influence of HL on the expression of CD42b on resting and thrombin-activated
      platelets was not found. However, increased level of fibrinogen but no influence
      of HL on fibrinogen concentration was observed in patients after ischemic stroke.
      Increased susceptibility to platelet agonists was found in patients after
      ischemic stroke in the convalescent phase. 

PMID- 25063765
TI  - Systematic analysis of bleeding phenotype in PT-VWD compared to type 2B VWD using
      an electronic bleeding questionnaire.
AB  - OBJECTIVE: To investigate the utility of an electronic version of the condensed
      molecular and clinical markers for the diagnosis and management of type 1 von
      Willebrand disease (VWD) bleeding questionnaire (eBQ) in assessing the bleeding
      phenotype in platelet-type VWD (PT-VWD) and compare it to its closely similar
      disorder, type 2B VWD. METHODS: Retrospective analysis of the clinical bleeding
      and laboratory phenotype of 13 patients with PT-VWD and 12 type 2B VWD. RESULTS:
      Bleeding score (BS) was significantly lower in PT-VWD as compared to type 2B.
      Bleeding score correlated with platelet count and von Willebrand
      factor:Ristocetin cofactor activity in PT-VWD but not in type 2B with a
      significant reduction in platelet count in type 2B VWD compared to PT-VWD. The
      eBQ had sensitivity of 62% in PT-VWD and 92% in type 2B VWD. CONCLUSION:
      Objective analysis of bleeding symptoms further the understanding of the
      phenotype of 2 closely similar bleeding disorders for better diagnosis and follow
      up. Larger international prospective studies are warranted to evaluate the
      utility of the eBQ in PT-VWD and other rare bleeding disorders.

PMID- 25063766
TI  - Red cell distribution width in patients with cerebral venous sinus thrombosis.

PMID- 25063767
TI  - Interactions Between Early Trauma and Catechol-O-Methyltransferase Genes on
      Inhibitory Deficits in Children With ADHD.
AB  - OBJECTIVE: To investigate the interaction between childhood trauma exposure with
      the catechol-O-methyltransferase (COMT) and dopamine receptor D4 (DRD4)
      polymorphisms in relation to neuropsychological measures in children with ADHD.
      METHOD: A cross-sectional examination of early traumatic experiences and the
      continuous performance test (CPT) were performed in 55 children with ADHD.
      Participants were also genotyped for the DRD4 exon III 48-bp variable number of
      tandem repeats (VNTR) polymorphism and the COMT Val158-Met (rs4680) polymorphism.
      RESULTS: There was significant interaction between the effects of the COMT
      genotype and trauma in commission errors. In participants with ADHD carrying the
      COMT Val/Val genotype, the group exposed to trauma showed significantly higher
      commission errors than the non-traumatized group. However, for the participants
      with other genotypes, no significant differences were found. CONCLUSION: This
      study suggests that there exists a genetic influence on the association between
      childhood trauma and the severity of inhibitory deficits in children with ADHD.

PMID- 25063768
TI  - Genome-wide profiling of the microRNA-mRNA regulatory network in skeletal muscle
      with aging.
AB  - Skeletal muscle degenerates progressively, losing mass (sarcopenia) over time,
      which leads to reduced physical ability and often results in secondary diseases
      such as diabetes and obesity. The regulation of gene expression by microRNAs is a
      key event in muscle development and disease. To understand genome-wide changes in
      microRNAs and mRNAs during muscle aging, we sequenced microRNAs and mRNAs from
      mouse gastrocnemius muscles at two different ages (6 and 24 months). Thirty-four
      microRNAs (15 up-regulated and 19 down-regulated) were differentially expressed
      with age, including the microRNAs miR-206 and -434, which were differentially
      expressed in aged muscle in previous studies. Interestingly, eight microRNAs in a
      microRNA cluster at the imprinted Dlk1-Dio3 locus on chromosome 12 were
      coordinately down-regulated. In addition, sixteen novel microRNAs were
      identified. Integrative analysis of microRNA and mRNA expression revealed that
      microRNAs may contribute to muscle aging through the positive regulation of
      transcription, metabolic processes, and kinase activity. Many of the age-related
      microRNAs have been implicated in human muscular diseases. We suggest that genome
      wide microRNA profiling will expand our knowledge of microRNA function in the
      muscle aging process.

PMID- 25063769
TI  - A role for SUV39H1-mediated H3K9 trimethylation in the control of genome
      stability and senescence in WI38 human diploid lung fibroblasts.
AB  - Cellular senescence has been associated with the age-dependent decline in tissue
      repair and regeneration, the increasing deterioration of the immune system, and
      the age-dependent increase in the incidence of cancer. Here, we show that
      senescence of human lung fibroblast WI-38 cells is associated with extensive
      changes to the gene expression profile, including the differential expression of
      transcriptional and epigenetic regulators. Among those,SUV39H1 was downregulated
      in senescent cells, correlated with a decrease in global H3K9 trimethylation,
      reduced H3K9me3 levels in repetitive DNA sequence regions such as satellites and
      transposable elements, and increased transcription of these repetitive DNA
      sequences. This indicates that SUV39H1 plays a role in limiting genomic
      instability in dividing cells and suggests that SUV39H1 downregulation may
      contribute to the establishment of senescence by increasing genomic instability.
      Additionally, the manipulation of SUV39H1 expression levels resulted in altered
      cell cycle distribution, suggesting a causal role of SUV39H1 in the establishment
      of cellular senescence. Thus, based on our findings and the results from previous
      reports, we propose a model in which SUV39H1 downregulation promotes the
      establishment of cellular senescence. 

PMID- 25063770
TI  - Does body mass index impact the early outcome of surgical revascularization? A
      comparison between off-pump and on-pump coronary artery bypass grafting.
AB  - OBJECTIVES: To investigate the effects of body mass index (BMI) on early outcomes
      after revascularization using either on-pump or off-pump surgery. METHODS: Data
      for 3714 of 4314 patients who underwent surgical revascularization at our
      institution between 1999 and 2008 were analysed. Patients were divided into two
      groups [off-pump coronary artery bypass (OPCAB); n = 1958 and on-pump coronary
      artery bypass (ONCAB); n = 1756] and further assigned into five classes according
      to their BMI (underweight <20 kg/m(2), normal 20-24.99 kg/m(2), overweight 25
      29.99 kg/m(2), obese 30-34.99 kg/m(2) and morbidly obese >=35 kg/m(2)). Thirty
      day mortality, occurrence of major adverse cardiac events (MACEs), occurrence of
      major non-cardiac adverse events (MNCAEs) and length of in-hospital stay were
      analysed in relation to BMI only (whole cohort analysis), to BMI and chosen
      surgical method (ONCAB versus OPCAB) as well as confounding factors. RESULTS: In
      the whole cohort analysis (n = 3714), no significant differences between BMI
      classes could be identified with regard to 30-day mortality (P = 0.78), MACEs (P
      = 0.72), MNCAEs (P = 0.45) or length of in-hospital stay (P = 0.94). With
      increasing BMI values, 30-day mortality tended to steadily increase (1.8% in BMI
      class 'underweight' vs 2.6% in BMI class 'morbidly obese'; P = 0.78), whereas
      MNCAEs tended to decrease with an increasing BMI (17.5% in BMI class
      'underweight' vs 12.2% in BMI class 'morbidly obese'; P = 0.45). Compared with
      ONCAB, in patients with higher BMI values, OPCAB appeared to reduce slightly the
      frequency of 30-day mortality, MACEs and MNCAEs, while slightly increasing the
      length of in-hospital stay. Adjustment for other risk factors by covariate
      analysis in multiple regression models did not change the inferences drawn.
      CONCLUSIONS: Our study did not detect significant differences between BMI classes
      with regard to mortality and morbidity. However, a slight trend towards a
      steadily increasing short-term mortality was detectable for patients with higher
      BMI values. When comparing ONCAB versus OPCAB, patients with higher BMI values
      appeared to have a weak tendency towards a reduced short-term morbidity and
      mortality in favour of OPCAB.

PMID- 25063771
TI  - WI-38 senescence is associated with global and site-specific hypomethylation.
AB  - Cellular senescence plays an important role in the age-dependent functional
      decline of organs and organ systems, as well as in age-related pathologies, such
      as cancer. Therefore, a better understanding of its underlying molecular
      mechanisms is crucial in the search for intervening measures. In this study, we
      considered the role of DNA methylation in senescence. We found that senescence is
      associated with global DNA hypomethylation, but also involves site-specific DNA
      hypo- and hypermethylation. In some cases, this differential methylation may
      affect gene expression and thereby modulate functional processes within cells.
      However, the majority of the CpG sites that were differentially methylated did
      not correspond with altered gene expression, suggesting that DNA methylation
      affects senescence by other means also, such as, for instance, genome stability. 

PMID- 25063772
TI  - Variation in nicotine intake among U.S. cigarette smokers during the past 25
      years: evidence from NHANES surveys.
AB  - OBJECTIVE: To estimate changes in nicotine intakes among U.S. cigarette smokers
      from 1988 to 2012 with the National Health and Nutrition Examination Survey
      (NHANES). METHODS: NHANES provides data on nationally representative samples of
      cigarette smokers from the civilian noninstitutionalized U.S. population. A total
      of 4,304 smokers aged 20 years and older were studied in NHANES III 1988-1994 and
      7,095 were studied in the continuous NHANES 1999-2012. We examined serum cotinine
      concentrations, daily cigarette consumption, and estimated nicotine intake per
      cigarette, with adjustment for sex, age, racial/ethnic background, level of
      education, and body mass index. RESULTS: There was little overall change in
      nicotine intake from smoking cigarettes either in the U.S. population as a whole
      or in major racial/ethnic subgroups during the 25-year period from 1988. Serum
      cotinine averaged 223.7ng/mL (95% confidence interval [CI] = 216.1-231.3) in 1988
      1994, which was not significantly different from the adjusted mean of 219.2ng/mL
      (95% CI = 214.1-224.4) in 1999-2012. During the same period, average daily
      cigarette consumption declined substantially, from 17.3 (95% CI = 16.5-18.0) in
      1988-1994 to 12.3 (95% CI = 11.0-13.6) by 2012. Cotinine per cigarette smoked
      increased by some 42% between 1988-1994 and 2011-2012, from a geometric mean of
      12.4 (95% CI = 11.7-13.1) to 17.6 (95% CI = 16.1-19.2). CONCLUSIONS: Reductions
      in cigarette smoking prevalence since the late 1980s, changes in cigarette
      product design, and the widespread introduction of smoke-free policies have not
      had a significant impact on nicotine intakes among U.S. smokers. Reductions in
      cigarette consumption have been offset by increased nicotine intake per cigarette
      smoked.

PMID- 25063773
TI  - Drug use, abuse, and dependence and the persistence of nicotine dependence.
AB  - INTRODUCTION: Illicit drug use and nicotine dependence (ND) frequently co-occur.
      Yet, to date very few studies have examined the role of alcohol and illicit drug
      use in ND persistence. The objectives of this study were to investigate the
      relationships between specific classes of drug use, abuse, and dependence and the
      persistence of ND over time among adults in the United States. METHODS: Data were
      drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a
      national survey of 34,653U.S. adults interviewed between 2001-2002 and
      reinterviewed 3 years later. Logistic regression analyses were used to
      investigate the relationships between various classes of drug use, abuse, and
      dependence among adults with ND at Wave 1 and the odds for persistent ND at Wave
      2. Analyses were adjusted for differences in demographic characteristics,
      mood/anxiety disorders, alcohol use disorders, and other substance use disorders.
      RESULTS: Lifetime drug use was not associated with significantly increased
      likelihood for persistent ND. Sedative abuse was associated with increased odds
      for nicotine persistence, but no other types of drug abuse were predictive of ND
      persistence, after adjusting for demographics, mood/anxiety, and alcohol use
      disorders. All types of drug dependence were associated with persistence of ND;
      the strongest associations emerged between opioid and tranquilizer dependence and
      persistent ND, while the associations between cannabis and cocaine dependence
      were no longer significant after adjusting for mood/anxiety disorders.
      CONCLUSIONS: Clinicians should take care to evaluate the presence and/or history
      of drug dependence among patients seeking treatment for smoking cessation. These
      data suggest that a history of substance dependence predicts increased
      vulnerability to persistent ND.

PMID- 25063775
TI  - Early prognosis of noise-induced hearing loss.
AB  - OBJECTIVE: Occupationally acquired noise-induced hearing loss (NIHL) is the most
      prevalent occupational disease in Austria and among the most common in many other
      countries. Because of the wide variation in hearing loss after equivalent
      exposures it has long been assumed that some individuals are more vulnerable to
      occupational NIHL than others. Earlier attempts to define predictors of NIHL
      before starting occupational noise exposure have largely failed. We present
      results of a prospective study evaluating the potential of temporary threshold
      shift (TTS) after a test exposure to predict NIHL. METHODS: Between 1982 and
      1989, overall 311 apprentices were included into a prospective study during their
      initial health screening visit. At this occasion, a standardised noise exposure
      was applied (20 min, 200-500 Hz, 100 dBA) and the TTS at 4 kHz was determined
      during at least 10 min after exposure. Hearing loss was monitored at follow-up
      visits every 3-5 years. Follow-up was 13 years on average. RESULTS: Permanent
      threshold shift was predicted by duration of noise exposure, frequency of wearing
      noise protectors and especially by the initial TTS at 4 kHz. Using 14 dB TTS as a
      cut-off had 82% sensitivity and 53% specificity to predict 20 dB or higher levels
      of NIHL. CONCLUSIONS: The TTS model can be successfully applied as a method to
      detect individuals at greater risk of occupational NIHL. It is recommended to
      routinely include such a procedure into initial workers' examinations for
      suitability to work under occupational noise conditions and for counselling on
      the use of hearing protectors.

PMID- 25063776
TI  - Nitrofurantoin retains antimicrobial activity against multidrug-resistant urinary
      Escherichia coli from US outpatients.
AB  - OBJECTIVES: To examine the prevalence of multidrug-resistant (MDR) urinary
      Escherichia coli among US outpatients and to assess the antimicrobial activity of
      oral antibiotics commonly used to treat urinary tract infections (UTIs) against
      MDR isolates. METHODS: Antimicrobial susceptibility testing data from outpatient
      urine cultures in The Surveillance Network (TSN) Database USA were analysed. Six
      antimicrobial agents from six separate drug classes were included: ampicillin,
      cefalotin, ciprofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole and
      amoxicillin/clavulanate. Isolates were categorized as resistant to one, two,
      three, four, five and six agents and compared for the years 2001 and 2010.
      Phenotypes of MDR isolates were assessed to determine antimicrobial activity of
      recommended therapy for UTIs. RESULTS: Prevalence of MDR E. coli increased from
      9.1% in 2001 (n = 29,198) to 17.0% in 2010 (n = 32,742) (P < 0.0001). In isolates
      that demonstrated resistance to three, four or five antimicrobial agents in 2010,
      resistance to nitrofurantoin was observed in only 2.1%, 7.5% and 24.1% of
      isolates, respectively. Conversely, widespread resistance was observed for
      trimethoprim/sulfamethoxazole (62.6%, 88.6% and 97.9% for isolates resistant to
      three, four and five agents, respectively) and ciprofloxacin (48.9%, 84.3% and
      98.2% for isolates resistant to three, four and five agents, respectively).
      CONCLUSIONS: Because of its consistent antimicrobial activity against MDR E.
      coli, nitrofurantoin remains a reliable first-line agent for the empirical
      treatment of acute uncomplicated cystitis.

PMID- 25063774
TI  - Growth hormone action predicts age-related white adipose tissue dysfunction and
      senescent cell burden in mice.
AB  - The aging process is associated with the development of several chronic diseases.
      White adipose tissue (WAT) may play a central role in age-related disease onset
      and progression due to declines in adipogenesis with advancing age. Recent
      reports indicate that the accumulation of senescent progenitor cells may be
      involved in age-related WAT dysfunction. Growth hormone (GH) action has profound
      effects on adiposity and metabolism and is known to influence lifespan. In the
      present study we tested the hypothesis that GH activity would predict age-related
      WAT dysfunction and accumulation of senescent cells. We found that long-lived GH
      deficient and -resistant mice have reduced age-related lipid redistribution.
      Primary preadipocytes from GH-resistant mice also were found to have greater
      differentiation capacity at 20 months of age when compared to controls. GH
      activity was also found to be positively associated with senescent cell
      accumulation in WAT. Our results demonstrate an association between GH activity,
      age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further
      studies are needed to determine if GH is directly inducing cellular senescence in
      WAT or if GH actions on other target organs or alternative downstream alterations
      in insulin-like growth factor-1, insulin or glucose levels are responsible. 

PMID- 25063777
TI  - Changes in subcutaneous adipose tissue microRNA expression in HIV-infected
      patients.
AB  - OBJECTIVES: We evaluated the possibility that a pattern of abnormal microRNA
      (miRNA) expression could be fuelling the mechanisms causing HIV-associated
      lipodystrophy (HAL). METHODS: In this case-control study, samples of subcutaneous
      adipose tissue from eight consecutive HIV-infected patients on combination
      antiretroviral therapy with HAL (cases) were compared with those of eight HIV
      negative subjects (controls). Human miRNA microarrays were used to probe the
      transcriptomes of the samples. Analysis of differentially expressed miRNAs was
      performed using DataAssist v2.0 software, applying a paired Student's t-test.
      RESULTS: Data showed that 21 miRNAs out of 754 were overexpressed in the patient
      group. Ten of these (i.e. miR-186, miR-199a-3p, miR-214, miR-374a, miR-487b, miR
      532-5p, miR-628-5p, miR-874, miR-125-b-1* and miR-374b*) were up-regulated to a
      significant degree (fold change >2.5; P < 0.01). Eleven other miRNAs (i.e. miR
      let-7d, miR-24, miR-30c, miR-125a-3p, miR-149, miR-191, miR-196-b, miR-218, miR
      342-3p, miR-452 and miR-454*) were 2- to 2.5-fold more expressed in HIV+ samples
      than in controls. Levels of mRNA for lipin 1, the target of miR-218, were
      significantly lower in subcutaneous adipose tissue from HIV patients.
      CONCLUSIONS: In adipocytes of HIV-infected patients, the up-regulation of
      specific miRNAs could lead to an increased 'activation' that might contribute to
      the pathogenesis of HAL by increasing cell turnover and/or promotion of
      apoptosis.

PMID- 25063778
TI  - Characterization of methicillin-resistant Staphylococcus sciuri isolates from
      industrially raised pigs, cattle and broiler chickens.
AB  - OBJECTIVES: This study aimed at assessing the epidemiology and genetic diversity
      of methicillin-resistant Staphylococcus sciuri (MRSS) from different farm animal
      species. METHODS: Nasal swabs were collected from 200 pigs, 100 dairy cows, 100
      beef cows, 150 veal calves and 200 broilers. Colonies were isolated on selective
      media containing cefoxitin and the mecA gene was detected by PCR. Antimicrobial
      resistance was determined by broth microdilution. The genetic diversity was
      assessed by PFGE and resistance and virulence genes were detected by microarray
      analysis. RESULTS: The total MRSS prevalence at the animal level was estimated at
      9.5%, varying from ~10% in veal (13.3%), broilers (12.5%) and dairy cows (10.0%)
      to 6.5% in pigs and 3.0% in beef cows. mecA was detected in all isolates. SCCmec
      elements of type III and non-typeable ones were seen most frequently. More than
      90% of isolates were non-wild-type (NWT) for gentamicin, penicillin, tiamulin,
      clindamycin and quinupristin/dalfopristin. The frequency of NWT isolates for
      fusidic acid and trimethoprim ranged between 78% and 87%. PFGE analysis allowed
      distinction between two major clusters. Most isolates tested by microarray
      carried erm and tet genes. Virulence genes were also detected, including an isa
      gene encoding an immune-evasion factor and the hsdS2 gene encoding a site
      specific deoxyribonuclease. CONCLUSIONS: This study shows that multiresistant
      MRSS is carried by different farm animal species. Although some animals shared
      the same strain, PFGE showed different patterns, indicating high diversity among
      the MRSS isolates recovered. The absence of clusters associated with a certain
      animal species suggests low host specificity.

PMID- 25063779
TI  - Efficacy and safety of daptomycin for the treatment of infectious disease: a meta
      analysis based on randomized controlled trials.
AB  - OBJECTIVES: A systematic review and meta-analysis based on randomized controlled
      trials (RCTs) of the efficacy and safety of daptomycin versus comparators.
      METHODS: Electronic databases (PubMed, Embase, Cochrane Central Register of
      Controlled Trials and clinical registered trials) were searched to identify RCTs
      that assessed the efficacy and safety of daptomycin versus therapy with
      comparators. Two reviewers independently applied selection criteria, performed a
      quality assessment and extracted the data. The I(2) statistic was calculated for
      heterogeneity, and a random-effects or fixed-effects model was used for estimates
      of risk ratio (RR). The primary outcome assessed was clinical treatment success
      among the intention-to-treat (ITT) population. RESULTS: Thirteen trials fulfilled
      the inclusion criteria. Daptomycin was as efficacious as comparator regimens
      among the ITT population (RR = 0.98, 95% CI 0.93-1.03) but had a lower efficacy
      among the clinically evaluable (CE) population (RR = 0.96, 95% CI 0.93-1.00).
      Subgroup analyses according to the quality of the trial, the type of antibiotic
      and the type of infection did not alter the outcomes. No significant difference
      was identified for all-cause mortality between the daptomycin and comparator
      groups (RR = 1.17, 95% CI 0.76-1.79) but daptomycin therapy did reduce the
      duration of treatment. Daptomycin caused a significantly lower incidence of renal
      impairment, nausea and headache but caused a reversible increase in creatine
      phosphokinase (CPK). Subgroup analysis indicated that daptomycin was
      significantly associated with a higher incidence of CPK elevation and fewer renal
      impairments among the population with a mean age <=60 years and a dose of
      daptomycin >=6 mg/kg/24 h. CONCLUSIONS: Daptomycin showed efficacy similar to the
      comparator regimens among the ITT population but lower efficacy among the CE
      population. Fewer adverse effects in total, but more CPK elevation effects, were
      observed in patients treated with daptomycin.

PMID- 25063780
TI  - Increased expression of SAMHD1 in a subset of HIV-1 elite controllers.
AB  - OBJECTIVES: SAMHD1 and the CDKN1A (p21) cyclin-dependent kinase inhibitor have
      been postulated to mediate HIV-1 restriction in CD4+ cells. We have shown that
      p21 affects HIV replication through its effect on SAMHD1. Thus, we aimed at
      evaluating the expression of SAMHD1 and p21 in different HIV+ phenotypic groups.
      PATIENTS AND METHODS: We evaluated SAMHD1 and CDKN1A mRNA expression in CD4+ T
      cells from HIV+ individuals including elite controllers (n = 12), individuals who
      control HIV without the need for antiretroviral treatment, viraemic progressors
      (n = 10) and HIV-1 seronegative healthy donors (n = 14). Immunological variables
      were measured by flow cytometry. RESULTS: We show that a subset of HIV+ elite
      controllers with lower T cell proliferation levels (Ki67+ cells) expressed higher
      SAMHD1 compared with healthy donors or viraemic progressors. Conversely, there
      was no difference in p21 expression before or after T cell activation with a
      bispecific CD3/CD8 antibody. CONCLUSIONS: Our results suggest that SAMHD1 may
      play a role in controlling virus replication in HIV+ individuals and slow the
      rate of disease progression.

PMID- 25063781
TI  - Emergence of quinolone resistance in the microbiota of hospitalized patients
      treated or not with a fluoroquinolone.
AB  - BACKGROUND: Quinolone resistance is a major global clinical problem. It primarily
      emerges in microbiota under selective pressure. Studies evaluating the incidence
      and risk factors for carrying quinolone-resistant bacteria in hospitalized
      patients treated with fluoroquinolones (FQs) are lacking. METHODS: We
      prospectively included hospitalized patients treated with FQs. Nasal, throat and
      rectal swabs were performed before FQ treatment, at the end of FQ treatment and
      30 days later. A 'reference group' of patients not receiving FQs was also
      included to determine the rates of quinolone resistance acquisition not linked to
      FQ treatment. Prevalence and incidence of quinolone-resistant strains of nasal
      coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, pharyngeal
      alpha-haemolytic streptococci and faecal Escherichia coli, and risk factors for
      emergence of quinolone resistance in FQ-treated patients were assessed. RESULTS:
      Four-hundred and fifty-one FQ-treated patients were included, as well as 119
      subjects in the 'reference group'. Emergence of quinolone resistance occurred in
      110/213 (51.6%), 50/336 (14.9%), 53/290 (18.3%) and 46/336 (13.7%) of FQ-treated
      patients for CoNS, S. aureus, alpha-haemolytic streptococci and E. coli,
      respectively, significantly more than for reference patients for CoNS (23/65; P <
      0.05), S. aureus (5/91; P < 0.02) and E. coli (4/84; P < 0.05), but not for alpha
      haemolytic streptococci (15/70; P = 0.55). Emergence of resistance was not
      associated with the type of FQ received, the duration of therapy or the duration
      of hospital stay, but was associated with host factors such as immunosuppression
      and altered performance status. CONCLUSIONS: FQs received during hospitalization
      account for high rates of emergence of resistance to FQs in clinically relevant
      bacteria from human microbiota, reflecting the important ecological impact of
      FQs. Host factors outweighed treatment or hospitalization characteristics as risk
      factors for carrying quinolone-resistant strains.

PMID- 25063782
TI  - A prominent role for RCAR3-mediated ABA signaling in response to Pseudomonas
      syringae pv. tomato DC3000 infection in Arabidopsis.
AB  - In plant-pathogen interaction, the plant hormone ABA can serve as a crucial
      modulator of plant responses to biotic as well as abiotic stress. Recent studies
      have identified pyrabactin resistance (PYR) 1/PYR1-like (PYL)/regulatory
      component of ABA receptor (RCAR) proteins as an ABA receptor that interacts with
      the protein phosphatase type 2C (PP2C) family. Here, we examined the functional
      involvement of ABA signaling components in pre- and post-invasive defense
      responses of Arabidopsis against the virulent pathogen Pseudomonas syringae pv.
      tomato (Pst) DC3000. Overexpression of the ABA receptor, RCAR3, enhanced
      susceptibility to Pst DC3000 by suppressing callose deposition and induction of
      salicylic acid (SA)-mediated pathogenesis-related (PR) genes, such as PR1 and
      NPR1, after syringe infiltration. In contrast, a dip inoculation assay revealed
      that RCAR3-overexpression mutants inhibited stomatal reopening during Pst DC3000
      infection and coronatine (COR) treatment, leading to enhanced resistance to Pst
      DC3000, which was not accompanied by differential expression of PR1 and NPR1
      genes. As a negative regulator of ABA signaling, PP2CA interacted with RCAR3 and
      its loss-of-function and overexpression mutants revealed that ABA sensitivity was
      positively correlated with stomatal immunity, similar to RCAR3 overexpression
      mutants. Taken together, these results suggest that RCAR3- and PP2CA-mediated ABA
      signaling antagonistically or synergistically contributes to the plant immune
      system throughout different phases of Pst DC3000 attack by SA or COR signaling
      cross-talk. 

PMID- 25063783
TI  - From the European indoor radon map towards an atlas of natural radiation.
AB  - In 2006, the Joint Research Centre of the European Commission launched a project
      to map radon at the European level, as part of a planned European Atlas of
      Natural Radiation. It started with a map of indoor radon concentrations. As of
      May 2014, this map includes data from 24 countries, covering a fair part of
      Europe. Next, a European map of geogenic radon, intended to show 'what earth
      delivers' in terms of radon potential (RP), was started in 2008. A first trial
      map has been created, and a database was established to collect all available
      data relevant to the RP. The Atlas should eventually display the geographical
      distribution of physical quantities related to natural radiation. In addition to
      radon, it will comprise maps of quantities such as cosmic rays and terrestrial
      gamma radiation. In this paper, the authors present the current state of the
      radon maps and the Atlas. 

PMID- 25063784
TI  - HER2-positive breast cancer patients: correlation between mammographic and
      pathological findings.
AB  - Human epidermal growth factor receptor 2 (HER2)-positive breast cancers represent
      a highly aggressive breast cancer subtype and are associated with a worse
      prognosis. This study was designed to investigate the mammography finding of HER2
      positive breast cancer and to compare the results with the characteristics of
      HER2-negative breast cancer patients. From January 2010 to October 2011,
      mammography findings of 65 patients with pathologically confirmed HER2-positive
      breast cancers (n = 22) or HER2-negative breast cancers (n = 43) were
      retrospectively reviewed. The authors also reviewed pathological reports for
      information on the histological type and differentiation grade. Among the two
      types of breast cancer patients, estrogen receptor-negative/PR-negative/HER2
      positive breast cancer patients most commonly had associated calcifications (18
      of 22) on mammography. On mammography, cases with a cluster of calcifications
      usually were presented as pleomorphic calcifications (12 of 20) and branching
      calcifications (4 of 20). Patients with HER2-positive breast cancers showed a
      histological grade II. HER2-positive breast cancer patients usually had ductal
      invasive carcinoma (17 of 22). Moreover, postmenopausal patients showed a
      significantly higher frequency of HER2-positive tumours. Our results suggest that
      the imaging findings might be useful in diagnosing HER2-positive breast cancer
      patients. 

PMID- 25063785
TI  - Performance of radiation survey meters in X- and gamma-radiation fields.
AB  - The aim of this work was to investigate the different types of radiation
      detectors commonly used for radiation protection purposes as survey meters. The
      study was performed on survey meters that use different detectors as ionisation
      chamber, Geiger Mueller (GM) counter and scintillation detector. For each survey
      meter, energy dependence and angular response in X- and gamma-radiation fields
      was tested. The following commercially available survey meters were investigated:
      ionisation chambers Victoreen 451P, Babyline 31 and VA-J-15A, Geiger counter MRK
      M87, 6150 AD6 and FAG FH 40F2 and scintillation counter 6150 ADB. As a source of
      gamma radiation, (137)Cs and (60)Co were used whereas X-ray radiation fields were
      generated using an X-ray unit. The radiation characteristics of the survey meters
      were mostly in compliance with references estimated by standard IEC 1017-2.
      However, some of them showed larger deviation at lower energies. GM counters
      exhibit strong energy dependence for low-energy photons. 

PMID- 25063786
TI  - Samarium-153 therapy for prostate cancer: the evaluation of urine activity, staff
      exposure and dose rate from patients.
AB  - The aim of this study was to determine the excretion of Samarium-153
      ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP) in urine and to
      calculate the dose rate of its retention in the body as a function of time and
      the dose received by the skin of laboratory staff's finger. Urine samples were
      collected from 11 patients after intravenous injection of (153)Sm-EDTMP. The
      measurements of dose rate were performed. Thermoluminescent dosemeters were used
      for absorbed dose measurements. Effective half-lives that were calculated from
      urine sample measurements were found as 7.1+/-3 h within the first 24 h. Whole
      body dose rates before collecting urine of patients were 60.0 +/- 15.7 uSv h(-1)
      for within 1 h following (153)Sm-EDTMP administration. The highest finger
      radiation dose is to the right-hand thumb (3.8 +/- 2 mGy). The results of the
      study imply that patients who recieved (153)Sm-EDTMP therapy should be kept a
      minumum of 8 h in an isolated room at hospital and that one staff should give
      therapy at most two patients per week. 

PMID- 25063787
TI  - Radiation doses in adult computed tomography practice in Serbia: initial results.
AB  - This work presents initial data on radiation doses in adult computed tomography
      (CT) in Serbia. Data were collected in terms of CT dose index (CTDIvol) and dose
      length product (DLP) values for head, chest and abdomen examination. The range of
      CTDIvol values was found to be 53-98, 11-34 and 8.5-227 mGy whereas for DLP was
      803-1066, 350-845 and 1066-3078 mGy cm(-1) for head, chest and abdomen
      examination, respectively. Except for abdomen on one CT unit, all estimated
      values were in line with the reported data. This work also presents simple method
      on how to reduce radiation doses when scanning head. Using axial (step-and-shot)
      instead of helical mode and decreasing tube current-time product leads to
      significant dose reduction. CTDIvol was decreased by 20 % whereas DLP was reduced
      for a factor 2. 

PMID- 25063788
TI  - Assessment of physician and patient (child and adult) equivalent doses during
      renal angiography by Monte Carlo method.
AB  - Renal angiography is one of the medical imaging methods in which patient and
      physician receive high equivalent doses due to long duration of fluoroscopy. In
      this research, equivalent doses of some radiosensitive tissues of patient (adult
      and child) and physician during renal angiography have been calculated by using
      adult and child Oak Ridge National Laboratory phantoms and Monte Carlo method
      (MCNPX). The results showed, in angiography of right kidney in a child and adult
      patient, that gall bladder with the amounts of 2.32 and 0.35 mSv, respectively,
      has received the most equivalent dose. About the physician, left hand, left eye
      and thymus absorbed the most amounts of doses, means 0.020 mSv. In addition,
      equivalent doses of the physician's lens eye, thyroid and knees were 0.023, 0.007
      and 7.9E-4 mSv, respectively. Although these values are less than the reported
      thresholds by ICRP 103, it should be noted that these amounts are related to one
      examination. 

PMID- 25063789
TI  - A computational physiology approach to personalized treatment models: the
      beneficial effects of slow breathing on the human cardiovascular system.
AB  - Heart rate variability biofeedback intervention involves slow breathing at a rate
      of ~6 breaths/min (resonance breathing) to maximize respiratory and baroreflex
      effects on heart period oscillations. This intervention has wide-ranging clinical
      benefits and is gaining empirical support as an adjunct therapy for biobehavioral
      disorders, including asthma and depression. Yet, little is known about the system
      level cardiovascular changes that occur during resonance breathing or the extent
      to which individuals differ in cardiovascular benefit. This study used a
      computational physiology approach to dynamically model the human cardiovascular
      system at rest and during resonance breathing. Noninvasive measurements of heart
      period, beat-to-beat systolic and diastolic blood pressure, and respiration
      period were obtained from 24 healthy young men and women. A model with
      respiration as input was parameterized to better understand how the
      cardiovascular processes that control variability in heart period and blood
      pressure change from rest to resonance breathing. The cost function used in model
      calibration corresponded to the difference between the experimental data and
      model outputs. A good match was observed between the data and model outputs
      (heart period, blood pressure, and corresponding power spectral densities).
      Significant improvements in several modeled cardiovascular functions (e.g., blood
      flow to internal organs, sensitivity of the sympathetic component of the
      baroreflex, ventricular elastance) were observed during resonance breathing.
      Individual differences in the magnitude and nature of these dynamic responses
      suggest that computational physiology may be clinically useful for tailoring
      heart rate variability biofeedback interventions for the needs of individual
      patients.

PMID- 25063790
TI  - Therapeutic angiogenesis by autologous adipose-derived regenerative cells:
      comparison with bone marrow mononuclear cells.
AB  - Transplantation of adipose-derived regenerative cell (ADRC) enhances ischemia
      induced angiogenesis, but the underlying mechanism remains unknown. Here, we
      compared the efficacy between ADRC and bone marrow mononuclear cell (BM-MNC)
      transplantation in rabbits model of hindlimb ischemia and examined the possible
      roles of alternative phenotypic macrophages polarization in ADRC-mediated
      angiogenesis using mice model of hindlimb ischemia. ADRCs and BM-MNCs were
      isolated from New Zealand White rabbits and C57BL/6J mice. In rabbit studies, our
      data showed that ADRCs could incorporate into the endothelial vasculature in
      vitro and in vivo. Both ADRC-conditioned media (CM) and BM-MNC-CM enhanced the
      migratory ability and interrupted the process of apoptosis in human umbilical
      vein endothelial cells. Four weeks after cell transplantation, augmentation of
      postnatal neovascularization was observed in the ischemic muscle injected with
      either ADRCs or BM-MNCs. In mice studies, we presented that ADRCs polarized into
      the IL-10-releasing M2 macrophages through PGE2-EP2/4 axis and suppressed the
      expressions of TNF-alpha and IL-6 in the ischemic muscle. Gene expressions of
      several angiogenic cytokines were amplified in the macrophages cultured in ADRC
      CM rather than BM-MNC-CM. Blockade of IL-10 using neutralizing MAb attenuated the
      ADRC-mediated angiogenesis and caused muscle apoptosis in vivo. In conclusion,
      ADRC transplantation harvested similar effect of neovascularization augmentation
      compared with BM-MNC in experimental rabbit model of hindlimb ischemia; ADRC
      displayed a unique immunoregulatory manner of accelerating IL-10-releasing M2
      macrophages polarization through the PGE2-EP2/4 axis. 

PMID- 25063791
TI  - Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic
      tolerance, and opioidergic cardioprotection.
AB  - Cholesterol-rich caveolar microdomains and associated caveolins influence
      sarcolemmal ion channel and receptor function and protective stress signaling.
      However, the importance of membrane cholesterol content to cardiovascular
      function and myocardial responses to ischemia-reperfusion (I/R) and
      cardioprotective stimuli are unclear. We assessed the effects of graded
      cholesterol depletion with methyl-beta-cyclodextrin (MbetaCD) and lifelong
      knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function,
      I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused
      hearts from young male C57Bl/6 mice were untreated or treated with 0.02-1.0 mM
      MbetaCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts
      were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective
      effects of morphine applied either acutely or chronically [sustained ligand
      activated preconditioning (SLP)] were assessed. MbetaCD concentration dependently
      reduced normoxic contractile function and postischemic outcomes in association
      with graded (10-30%) reductions in sarcolemmal cholesterol. Cardioprotection with
      acute morphine was abolished with >=20 MUM MbetaCD, whereas SLP was more robust
      and only inhibited with >=200 MUM MbetaCD. Deletion of Cav-3 also reduced,
      whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained
      equally effective in Cav-3 KO mice and was additive with innate protection
      arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of
      normoxic myocardial and coronary function, I/R tolerance, and OR-mediated
      cardioprotection in murine hearts (all declining with cholesterol depletion). In
      contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R
      tolerance parallels Cav-3 expression. Novel SLP appears unique, being less
      sensitive to cholesterol depletion than acute OR protection and arising
      independently of Cav-3 expression. 

PMID- 25063792
TI  - Poldip2 controls vascular smooth muscle cell migration by regulating focal
      adhesion turnover and force polarization.
AB  - Polymerase-delta-interacting protein 2 (Poldip2) interacts with NADPH oxidase 4
      (Nox4) and regulates migration; however, the precise underlying mechanisms are
      unclear. Here, we investigated the role of Poldip2 in focal adhesion turnover, as
      well as traction force generation and polarization. Poldip2 overexpression
      (AdPoldip2) in vascular smooth muscle cells (VSMCs) impairs PDGF-induced
      migration and induces a characteristic phenotype of long cytoplasmic extensions.
      AdPoldip2 also prevents the decrease in spreading and increased aspect ratio
      observed in response to PDGF and slightly impairs cell contraction. Moreover,
      AdPoldip2 blocks focal adhesion dissolution and sustains H2O2 levels in focal
      adhesions, whereas Poldip2 knockdown (siPoldip2) significantly decreases the
      number of focal adhesions. RhoA activity is unchanged when focal adhesion
      dissolution is stimulated in control cells but increases in AdPoldip2-treated
      cells. Inhibition of RhoA blocks Poldip2-mediated attenuation of focal adhesion
      dissolution, and overexpression of RhoA or focal adhesion kinase (FAK) reverses
      the loss of focal adhesions induced by siPoldip2, indicating that RhoA and FAK
      mediate the effect of Poldip2 on focal adhesions. Nox4 silencing prevents focal
      adhesion stabilization by AdPoldip2 and induces a phenotype similar to siPoldip2,
      suggesting a role for Nox4 in Poldip2-induced focal adhesion stability. As a
      consequence of impaired focal adhesion turnover, PDGF-treated AdPoldip2 cells are
      unable to reduce and polarize traction forces, a necessary first step in
      migration. These results implicate Poldip2 in VSMC migration via regulation of
      focal adhesion turnover and traction force generation in a Nox4/RhoA/FAK
      dependent manner.

PMID- 25063793
TI  - Repeated daily dosing with sildenafil provides sustained protection from
      endothelial dysfunction caused by ischemia and reperfusion: a human in vivo
      study.
AB  - Sildenafil and nitroglycerin (GTN) are effective pharmacological preconditioning
      agents, protecting from the adverse effects of ischemia and reperfusion (I/R).
      The objective of the present study was to determine whether repeated, daily
      administration of sildenafil or GTN provides sustained preconditioning from I/R
      in the human forearm vasculature. Thirty-six healthy volunteers participated in
      this investigator-blind, randomized, placebo-controlled trial. Subjects received
      transdermal GTN (0.6 mg/h, 2 h/day), sildenafil (50 mg once daily), or placebo.
      Twenty-four hours after the first dose of medication, subjects underwent an
      assessment of flow-mediated dilation (FMD) before and after I/R (15 min of upper
      arm ischemia followed by 15 min of reperfusion). Subjects continued their study
      medication for 7 days, at which point FMD measurements were repeated before and
      after I/R. Venous blood samples were obtained for the determination of
      myeloperoxidase, P-selectin, and myoglobin before and after each I/R episode.
      Twenty-four hours after the first dose, both sildenafil and GTN (but not placebo)
      provided protection from the adverse effects of I/R. After 7 days of repeated
      daily doses and 24 h after the last dose, FMD was significantly blunted after I/R
      in placebo- and GTN-treated groups. In contrast, repeated daily administration of
      sildenafil provided continued protection from the adverse effects of I/R on
      endothelial function. There was no significant change in plasma levels of
      myeloperoxidase, P-selectin, or myoglobin at any time point. In conclusion, the
      present study establishes, for the first time in humans, that sildenafil, but not
      GTN, provides sustained pharmacological preconditioning of the endothelium and
      protection from adverse I/R effects on vascular function. 

PMID- 25063794
TI  - Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional
      sympathetic outputs via NTS adenosine receptors.
AB  - Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor
      subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits
      cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via
      different mechanisms: direct inhibition of glutamate release and facilitation of
      an inhibitory neurotransmitter release, respectively. However, it remains unknown
      whether adenosine naturally released into the NTS has similar inhibitory effects
      on the CCR as the exogenous agonists do. Our previous study showed that adenosine
      is released into the NTS during severe hemorrhage and contributes to reciprocal
      changes of renal (decreases) and adrenal (increases) sympathetic nerve activity
      observed in this setting. Both A1 and A2a adenosine receptors are involved.
      Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control
      of the two sympathetic outputs is attenuated by adenosine naturally released into
      the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by
      right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 MUg/kg)
      under control conditions, during hemorrhage, and during hemorrhage preceded by
      blockade of NTS adenosine receptors with bilateral microinjections of 8-(p
      sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized
      rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was
      significantly attenuated during severe hemorrhage despite reciprocal changes in
      the baseline activity levels, and this attenuation was removed by bilateral
      blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine
      endogenously released into the NTS has a similar modulatory effect on integration
      of cardiovascular reflexes as stimulation of NTS adenosine receptors with
      exogenous agonists. 

PMID- 25063795
TI  - The low frequency power of heart rate variability is neither a measure of cardiac
      sympathetic tone nor of baroreflex sensitivity.
AB  - The lack of noninvasive approaches to measure cardiac sympathetic nerve activity
      (CSNA) has driven the development of indirect estimates such as the low-frequency
      (LF) power of heart rate variability (HRV). Recently, it has been suggested that
      LF HRV can be used to estimate the baroreflex modulation of heart period (HP)
      rather than cardiac sympathetic tone. To test this hypothesis, we measured CSNA,
      HP, blood pressure (BP), and baroreflex sensitivity (BRS) of HP, estimated with
      the modified Oxford technique, in conscious sheep with pacing-induced heart
      failure and in healthy control sheep. We found that CSNA was higher and systolic
      BP and HP were lower in sheep with heart failure than in control sheep. Cross
      correlation analysis showed that in each group, the beat-to-beat changes in HP
      correlated with those in CSNA and in BP, but LF HRV did not correlate
      significantly with either CSNA or BRS. However, when control sheep and sheep with
      heart failure were considered together, CSNA correlated negatively with HP and
      BRS. There was also a negative correlation between CSNA and BRS in control sheep
      when considered alone. In conclusion, we demonstrate that in conscious sheep, LF
      HRV is neither a robust index of CSNA nor of BRS and is outperformed by HP and
      BRS in tracking CSNA. These results do not support the use of LF HRV as a
      noninvasive estimate of either CSNA or baroreflex function, but they highlight a
      link between CSNA and BRS.

PMID- 25063796
TI  - Hemodynamic performance of the Fontan circulation compared with a normal
      biventricular circulation: a computational model study.
AB  - The physiological limitations of the Fontan circulation have been extensively
      addressed in the literature. Many studies emphasized the importance of pulmonary
      vascular resistance in determining cardiac output (CO) but gave little attention
      to other cardiovascular properties that may play considerable roles as well. The
      present study was aimed to systemically investigate the effects of various
      cardiovascular properties on clinically relevant hemodynamic variables (e.g., CO
      and central venous pressure). To this aim, a computational modeling method was
      employed. The constructed models provided a useful tool for quantifying the
      hemodynamic effects of any cardiovascular property of interest by varying the
      corresponding model parameters in model-based simulations. Herein, the Fontan
      circulation was studied compared with a normal biventricular circulation so as to
      highlight the unique characteristics of the Fontan circulation. Based on a series
      of numerical experiments, it was found that 1) pulmonary vascular resistance,
      ventricular diastolic function, and systemic vascular compliance play a major
      role, while heart rate, ventricular contractility, and systemic vascular
      resistance play a secondary role in the regulation of CO in the Fontan
      circulation; 2) CO is nonlinearly related to any single cardiovascular property,
      with their relationship being simultaneously influenced by other cardiovascular
      properties; and 3) the stability of central venous pressure is significantly
      reduced in the Fontan circulation. The findings suggest that the hemodynamic
      performance of the Fontan circulation is codetermined by various cardiovascular
      properties and hence a full understanding of patient-specific cardiovascular
      conditions is necessary to optimize the treatment of Fontan patients.

PMID- 25063797
TI  - Systemic microvascular shunting through hyperdynamic capillaries after acute
      physiological disturbances following cardiopulmonary bypass.
AB  - Previously we showed that cardiopulmonary bypass (CPB) during cardiac surgery is
      associated with reduced sublingual microcirculatory perfusion and oxygenation. It
      has been suggested that impaired microcirculatory perfusion may be paralleled by
      increased heterogeneity of flow in the microvascular bed, possibly leading to
      arteriovenous shunting. Here we investigated our hypothesis that acute
      hemodynamic disturbances during extracorporeal circulation indeed lead to
      microcirculatory heterogeneity with hyperdynamic capillary perfusion and reduced
      systemic oxygen extraction. In this single-center prospective observational
      study, patients undergoing cardiac surgery with (n = 18) or without (n = 13) CPB
      were included. Perioperative microcirculatory perfusion was assessed sublingually
      with sidestream darkfield imaging, and recordings were quantified for
      microcirculatory heterogeneity and hyperdynamic capillary perfusion. The
      relationship with hemodynamic and oxygenation parameters was analyzed.
      Microcirculatory heterogeneity index increased substantially after onset of CPB
      [0.5 (0.0-0.9) to 1.0 (0.3-1.3); P = 0.031] but not during off-pump surgery.
      Median capillary red blood cell (RBC) velocity increased intraoperatively in the
      CPB group only [1,600 (913-2,500 MUm/s) vs. 380 (190-480 MUm/s); P < 0.001], with
      31% of capillaries supporting high RBC velocities (>2,000 MUm/s). Hyperdynamic
      microcirculatory perfusion was associated with reduced arteriovenous oxygen
      difference and systemic oxygen consumption during and after CPB. The current
      study provides the first direct human evidence for a microvascular shunting
      phenomenon through hyperdynamic capillaries following acute physiological
      disturbances after onset of CPB. The hypothesis of impaired systemic oxygen
      offloading caused by hyperdynamic capillaries was supported by reduced blood
      arteriovenous oxygen difference and low systemic oxygen extraction associated
      with CPB.

PMID- 25063798
TI  - Sustained mitochondrial functioning in cerebral arteries after transient ischemic
      stress in the rat: a potential target for therapies.
AB  - The objective of the present study was to determine whether mitochondrial
      function in the cerebral vasculature is maintained after transient middle
      cerebral artery (MCA) occlusion (tMCAO) in rats. Sprague-Dawley rats were exposed
      to 90 min of tMCAO followed by 4 or 48 h of reperfusion. MCAs from ischemic
      (ipsilateral) and nonischemic (contralateral) sides were compared with control
      MCAs from sham-operated rats. We determined 1) vasoreactivity to diazoxide (DZ; a
      mitochondrial ATP-activated K(+) channel opener), ACh, bradykinin (BK),
      serotonin, and sodium nitroprusside; 2) levels of mitochondrial and
      nonmitochondrial proteins and mitochondrial DNA; and 3) vascular levels of
      tetramethylrhodamine ethyl ester (an indicator of mitochondrial membrane
      potential). All dilator responses, including those with DZ, were intact 4 h post
      tMCAO. Dilator responses to ACh, BK, and sodium nitroprusside were reduced in
      ipsilateral MCAs at 48 h compared with contralateral MCAs, but DZ responses were
      comparable with control MCAs. Surprisingly, contralateral responses to ACh, BK,
      and serotonin were reduced compared with control MCAs at 48 h. Ipsilateral
      vasodilation to DZ at 48 h was eliminated by endothelial denudation and
      endothelial nitric oxide synthase (eNOS) inhibition but was only reduced in
      control MCAs. Mitochondrial proteins, phosphorylated eNOS, mitochondrial DNA, and
      mitochondrial membrane potential were higher in ipsilateral compared with
      contralateral MCAs. In conclusion, contrary to conventional wisdom, mitochondria
      remain functional for at least 48 h after severe ischemic stress in MCAs, and DZ
      induced dilation is preserved due to maintained mitochondrial mass, probably in
      the endothelium, and eNOS signaling. Our findings support the concept that
      functioning vascular mitochondria are an unexpected target for novel stroke
      therapies.

PMID- 25063799
TI  - alpha-Klotho protects against oxidative damage in pulmonary epithelia.
AB  - alpha-Klotho exerts pleiotropic biological actions. Heterozygous alpha-Klotho
      haplo-insufficient mice (kl/+) appear normal at baseline except for age-related
      changes in the lung, suggesting heightened pulmonary susceptibility to alpha
      Klotho deficiency. We used in vivo and in vitro models to test whether alpha
      Klotho protects lung epithelia against injury. Normally, alpha-Klotho is not
      expressed in the lung, but circulating alpha-Klotho levels are reduced -40% in
      kl/+ mice and undetectable in homozygous alpha-Klotho-deficient mice (kl/kl).
      kl/+ mice show distal air space enlargement at a given airway pressure, with
      elevated lung oxidative damage marker (8-hydroxydeoxyguanosine; 8-OHdG); these
      abnormalities are exacerbated in kl/kl mice. Studies were performed in A549 lung
      epithelial cells and/or primary culture of alveolar epithelial cells. Hyperoxia
      (95% O2) and high inorganic phosphate concentrations (Pi, 3-5 mM) additively
      caused cell injury (lactate dehydrogenase release), oxidative DNA damage (8
      OHdG), lipid oxidation (8-isoprostane), protein oxidation (carbonyl), and
      apoptosis (caspase-8 activity and TUNEL stain). Transfection of transmembrane or
      soluble alpha-Klotho, or addition of soluble alpha-Klotho-containing conditioned
      media, increased cellular antioxidant capacity (Cu- and Fe-based assays) via
      increased nuclear factor erythroid-derived 2-related factors 1 and 2 (Nrf1/2)
      transcriptional activity and ameliorated hyperoxic and phosphotoxic injury. To
      validate the findings in vivo, we injected alpha-Klotho-containing conditioned
      media into rat peritoneum before and during hyperoxia exposure and found reduced
      alveolar interstitial edema and oxidative damage. We conclude that circulating
      alpha-Klotho protects the lung against oxidative damage and apoptosis partly via
      increasing endogenous antioxidative capacity in pulmonary epithelia.
      Cytoprotection by alpha-Klotho may play an important role in degenerative
      diseases of the lung.

PMID- 25063800
TI  - Ozone-induced airway epithelial cell death, the neurokinin-1 receptor pathway,
      and the postnatal developing lung.
AB  - Children are uniquely susceptible to ozone because airway and lung growth
      continue for an extensive period after birth. Early-life exposure of the rhesus
      monkey to repeated ozone cycles results in region-specific disrupted airway/lung
      growth, but the mediators and mechanisms are poorly understood. Substance P (SP),
      neurokinin-1 receptor (NK-1R); and nuclear receptor Nur77 (NR4A1) are signaling
      pathway components involved in ozone-induced cell death. We hypothesize that
      acute ozone (AO) exposure during postnatal airway development disrupts SP/NK
      1R/Nur77 pathway expression and that these changes correlate with increased ozone
      induced cell death. Our objectives were to 1) spatially define the normal
      development of the SP/NK-1R/Nur77 pathway in conducting airways; 2) compare how
      postnatal age modulates responses to AO exposure; and 3) determine how
      concomitant, episodic ozone exposure modifies age-specific acute responses. Male
      infant rhesus monkeys were assigned at age 1 mo to two age groups, 2 or 6 mo, and
      then to one of three exposure subgroups: filtered air (FA), FA+AO (AO: 8 h/day *
      2 days), or episodic biweekly ozone exposure cycles (EAO: 8 h/day * 5 days/14-day
      cycle+AO). O3 = 0.5 ppm. We found that 1) ozone increases SP/NK-1R/Nur77 pathway
      expression in conducting airways, 2) an ozone exposure cycle (5 days/cycle)
      delivered early at age 2 mo resulted in an airway that was hypersensitive to AO
      exposure at the end of 2 mo, and 3) continued episodic exposure (11 cycles)
      resulted in an airway that was hyposensitive to AO exposure at 6 mo. These
      observations collectively associate with greater overall inflammation and
      epithelial cell death, particularly in early postnatal (2 mo), distal airways. 

PMID- 25063801
TI  - Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133+
      progenitor cells self-renewal and stimulates their accumulation in the lungs of
      pulmonary hypertensive rats.
AB  - Although hypoxia is detrimental to most cell types, it aids survival of
      progenitor cells and is associated with diseases like cancer and pulmonary
      hypertension in humans. Therefore, understanding the underlying mechanisms that
      promote survival of progenitor cells in hypoxia and then developing novel
      therapies to stop their growth in hypoxia-associated human diseases is important.
      Here we demonstrate that the proliferation and growth of human CD133(+)
      progenitor cells, which contribute to tumorigenesis and the development of
      pulmonary hypertension, are increased when cultured under hypoxic conditions.
      Furthermore, glucose-6-phosphate dehydrogenase (G6PD) activity was increased
      threefold in hypoxic CD133(+) cells. The increased G6PD activity was required for
      CD133(+) cell proliferation, and their growth was arrested by G6PD inhibition or
      knockdown. G6PD activity upregulated expression of HIF1alpha, cyclin A, and
      phospho-histone H3, thereby promoting CD133(+) cell dedifferentiation and self
      renewal and altering cell cycle regulation. When CD133(+) cells were cocultured
      across a porous membrane from pulmonary artery smooth muscle cells (PASMCs), G6PD
      dependent H2O2 production and release by PASMCs recruited CD133(+) cells to the
      membrane, where they attached and expressed smooth muscle markers (alpha-actin
      and SM22alpha). Inhibition of G6PD reduced smooth muscle marker expression in
      CD133(+) cells under normoxia but not hypoxia. In vivo, CD133(+) cells
      colocalized with G6PD(+) cells in the perivascular region of lungs from rats with
      hypoxia-induced pulmonary hypertension. Finally, inhibition of G6PD by
      dehydroepiandrosterone in pulmonary arterial hypertensive rats nearly abolished
      CD133(+) cell accumulation around pulmonary arteries and the formation of
      occlusive lesions. These observations suggest G6PD plays a key role in increasing
      hypoxia-induced CD133(+) cell survival in hypertensive lungs that differentiate
      to smooth muscle cells and contribute to pulmonary arterial remodeling during
      development of pulmonary hypertension.

PMID- 25063802
TI  - Rescuing DeltaF508 CFTR with trimethylangelicin, a dual-acting corrector and
      potentiator.
AB  - Since the discovery of the cystic fibrosis (CF) gene that encodes the CF
      transmembrane conductance regulator (CFTR) in 1989, there has been considerable
      progress in understanding the molecular defects associated with different
      mutations in the CFTR protein. Small molecule "potentiators" have led the way as
      a drug therapeutic approach for correcting channel gating mutations such as the
      G551D mutation. Therapies for correcting the most common folding mutation in
      CFTR, DeltaF508, however, have proven to be much more challenging. The protein
      folding problem appears to be associated with both nucleotide binding domain
      (NBD) instability and domain interface interactions that are caused by the loss
      of the phenylalanine residue in NBD 1. Given the inherent complexity in the
      sequential folding pathway for this very large multidomain protein, it has been
      suggested that correcting the proper folding, anion channel function, and cell
      surface stability of the DeltaF508 CFTR protein will require a multidrug approach
      to fix each of these compounding problems. Here we discuss a recent publication
      (Favia M, Mancini MT, Bezzerri V, Guerra L, Laselva O, Abbattiscianni AC,
      Debellis L, Reshkin SJ, Gambari R, Cabrini G, Casavola V. Am J Physiol Lung Cell
      Mol Physiol 307: L48-L61, 2014), however, that offers hope that single drug
      therapies are still possible. 

PMID- 25063803
TI  - Increase in nucleus accumbens dopamine levels following local ethanol
      administration is not mediated by acetaldehyde.
AB  - AIMS: Ethanol (EtOH) activates the mesolimbic dopamine system and increases
      dopamine levels in the nucleus accumbens (nAc), which is believed to underlie the
      rewarding effects of alcohol. Accumulating evidence now implicates that
      acetaldehyde, the first metabolite of EtOH, may play an important role in
      mediating some of the rewarding properties of its parent compound. The objective
      of this study was to investigate if the increase in accumbal dopamine output
      observed when administering EtOH locally in the nAc by reversed microdialysis is
      mediated by acetaldehyde. METHODS: Acetaldehyde (1, 10, 100 or 200 uM) or EtOH
      (300 mM) was administered via reversed microdialysis in the nAc of male Wistar
      rats. In a separate experiment, animals were administered EtOH (300 mM) in the
      nAc, following pre-treatment with the acetaldehyde-sequestering agent d
      penicillamine (50 mg/kg injected intraperitoneally 60 min before drug challenge).
      Microdialysates from the nAc were collected every 20 min and dopamine content was
      quantified using high-performance liquid chromatography. RESULTS: Acetaldehyde
      administered in the nAc did not influence accumbal dopamine levels at any of the
      concentrations applied, whereas EtOH induced a significant increase in accumbal
      dopamine. The dopamine-elevating properties of EtOH were not attenuated by pre
      treatment with d-penicillamine. CONCLUSION: The current results show that EtOH
      administered in the nAc induces an elevation in accumbal dopamine levels, which
      is not mimicked by acetaldehyde alone, nor is it influenced by acetaldehyde
      sequestering. This would suggest that the increase in accumbal dopamine following
      nAc EtOH administration is not mediated by acetaldehyde.

PMID- 25063804
TI  - The HIV-1 integrase mutant R263A/K264A is 2-fold defective for TRN-SR2 binding
      and viral nuclear import.
AB  - Transportin-SR2 (Tnpo3, TRN-SR2), a human karyopherin encoded by the TNPO3 gene,
      has been identified as a cellular cofactor of HIV-1 replication, specifically
      interacting with HIV-1 integrase (IN). Whether this interaction mediates the
      nuclear import of HIV remains controversial. We previously characterized the TRN
      SR2 binding interface in IN and introduced mutations at these positions to
      corroborate the biological relevance of the interaction. The pleiotropic nature
      of IN mutations complicated the interpretation. Indeed, all previously tested IN
      interaction mutants also affected RT. Here we report on a virus with a pair of IN
      mutations, IN(R263A/K264A), that significantly reduce interaction with TRN-SR2.
      The virus retains wild-type reverse transcription activity but displays a block
      in nuclear import and integration, as measured by quantitative PCR. The defect in
      integration of this mutant resulted in a smaller increase in the number of two
      long terminal repeat circles than for virus specifically blocked at integration
      by raltegravir or catalytic site mutations (IN(D64N/D116N/E152Q)). Finally, using
      an eGFP-IN-labeled HIV fluorescence-based import assay, the defect in nuclear
      import was corroborated. These data altogether underscore the importance of the
      HIV-IN TRN-SR2 protein-protein interaction for HIV nuclear import and validate
      the IN/TRN-SR2 interaction interface as a promising target for future antiviral
      therapy. 

PMID- 25063805
TI  - A novel functional site in the PB2 subunit of influenza A virus essential for
      acetyl-CoA interaction, RNA polymerase activity, and viral replication.
AB  - The PA, PB1, and PB2 subunits, components of the RNA-dependent RNA polymerase of
      influenza A virus, are essential for viral transcription and replication. The PB2
      subunit binds to the host RNA cap (7-methylguanosine triphosphate (m(7)GTP)) and
      supports the endonuclease activity of PA to "snatch" the cap from host pre-mRNAs.
      However, the structure of PB2 is not fully understood, and the functional sites
      remain unknown. In this study, we describe a novel Val/Arg/Gly (VRG) site in the
      PB2 cap-binding domain, which is involved in interaction with acetyl-CoA found in
      eukaryotic histone acetyltransferases (HATs). In vitro experiments revealed that
      the recombinant PB2 cap-binding domain that includes the VRG site interacts with
      acetyl-CoA; moreover, it was found that this interaction could be blocked by CoA
      and various HAT inhibitors. Interestingly, m(7)GTP also inhibited this
      interaction, suggesting that the same active pocket is capable of interacting
      with acetyl-CoA and m(7)GTP. To elucidate the importance of the VRG site on PB2
      function and viral replication, we constructed a PB2 recombinant protein and
      recombinant viruses including several patterns of amino acid mutations in the VRG
      site. Substitutions of the valine and arginine residues or of all 3 residues of
      the VRG site to alanine significantly reduced the binding ability of PB2 to
      acetyl-CoA and its RNA polymerase activity. Recombinant viruses containing the
      same mutations could not be replicated in cultured cells. These results indicate
      that the PB2 VRG sequence is a functional site that is essential for acetyl-CoA
      interaction, RNA polymerase activity, and viral replication. 

PMID- 25063806
TI  - The N- and C-terminal domains of tomosyn play distinct roles in soluble N
      ethylmaleimide-sensitive factor attachment protein receptor binding and fusion
      regulation.
AB  - Tomosyn negatively regulates SNARE-dependent exocytic pathways including insulin
      secretion, GLUT4 exocytosis, and neurotransmitter release. The molecular
      mechanism of tomosyn, however, has not been fully elucidated. Here, we
      reconstituted SNARE-dependent fusion reactions in vitro to recapitulate the
      tomosyn-regulated exocytic pathways. We then expressed and purified active full
      length tomosyn and examined how it regulates the reconstituted SNARE-dependent
      fusion reactions. Using these defined fusion assays, we demonstrated that tomosyn
      negatively regulates SNARE-mediated membrane fusion by inhibiting the assembly of
      the ternary SNARE complex. Tomosyn recognizes the t-SNARE complex and prevents
      its pairing with the v-SNARE, therefore arresting the fusion reaction at a pre
      docking stage. The inhibitory function of tomosyn is mediated by its C-terminal
      domain (CTD) that contains an R-SNARE-like motif, confirming previous studies
      carried out using truncated tomosyn fragments. Interestingly, the N-terminal
      domain (NTD) of tomosyn is critical (but not sufficient) to the binding of
      tomosyn to the syntaxin monomer, indicating that full-length tomosyn possesses
      unique features not found in the widely studied CTD fragment. Finally, we showed
      that the inhibitory function of tomosyn is dominant over the stimulatory activity
      of the Sec1/Munc18 protein in fusion. We suggest that tomosyn uses its CTD to
      arrest SNARE-dependent fusion reactions, whereas its NTD is required for the
      recruitment of tomosyn to vesicle fusion sites through syntaxin interaction. 

PMID- 25063807
TI  - Mitogen-activated protein kinase (MAPK) hyperactivation and enhanced NRAS
      expression drive acquired vemurafenib resistance in V600E BRAF melanoma cells.
AB  - Although targeting the V600E activating mutation in the BRAF gene, the most
      common genetic abnormality in melanoma, has shown clinical efficacy in melanoma
      patients, response is, invariably, short lived. To better understand mechanisms
      underlying this acquisition of resistance to BRAF-targeted therapy in previously
      responsive melanomas, we induced vemurafenib resistance in two V600E BRAF+ve
      melanoma cell lines, A375 and DM443, by serial in vitro vemurafenib exposure. The
      resulting approximately 10-fold more vemurafenib-resistant cell lines, A375rVem
      and D443rVem, had higher growth rates and showed differential collateral
      resistance to cisplatin, melphalan, and temozolomide. The acquisition of
      vemurafenib resistance was associated with significantly increased NRAS levels in
      A375rVem and D443rVem, increased activation of the prosurvival protein, AKT, and
      the MAPKs, ERK, JNK, and P38, which correlated with decreased levels of the MAPK
      inhibitor protein, GSTP1. Despite the increased NRAS, whole exome sequencing
      showed no NRAS gene mutations. Inhibition of all three MAPKs and siRNA-mediated
      NRAS suppression both reversed vemurafenib resistance significantly in A375rVem
      and DM443rVem. Together, the results indicate a mechanism of acquired vemurafenib
      resistance in V600E BRAF+ve melanoma cells that involves increased activation of
      all three human MAPKs and the PI3K pathway, as well as increased NRAS expression,
      which, contrary to previous reports, was not associated with mutations in the
      NRAS gene. The data highlight the complexity of the acquired vemurafenib
      resistance phenotype and the challenge of optimizing BRAF-targeted therapy in
      this disease. They also suggest that targeting the MAPKs and/or NRAS may provide
      a strategy to mitigate such resistance in V600E BRAF+ve melanoma. 

PMID- 25063808
TI  - Liver clock protein BMAL1 promotes de novo lipogenesis through insulin-mTORC2-AKT
      signaling.
AB  - The clock protein BMAL1 (brain and muscle Arnt-like protein 1) participates in
      circadian regulation of lipid metabolism, but its contribution to insulin AKT
      regulated hepatic lipid synthesis is unclear. Here we used both Bmal1(-/-) and
      acute liver-specific Bmal1-depleted mice to study the role of BMAL1 in refeeding
      induced de novo lipogenesis in the liver. Both global deficiency and acute
      hepatic depletion of Bmal1 reduced lipogenic gene expression in the liver upon
      refeeding. Conversely, Bmal1 overexpression in mouse liver by adenovirus was
      sufficient to elevate the levels of mRNA of lipogenic enzymes. Bmal1(-/-) primary
      mouse hepatocytes displayed decreased levels of de novo lipogenesis and lipogenic
      enzymes, supporting the notion that BMAL1 regulates lipid synthesis in
      hepatocytes in a cell-autonomous manner. Both refed mouse liver and insulin
      treated primary mouse hepatocytes showed impaired AKT activation in the case of
      either Bmal1 deficiency or Bmal1 depletion by adenoviral shRNA. Restoring AKT
      activity by a constitutively active mutant of AKT nearly normalized de novo
      lipogenesis in Bmal1(-/-) hepatocytes. Finally, Bmal1 deficiency or knockdown
      decreased the protein abundance of RICTOR, the key component of the mTORC2
      complex, without affecting the gene expression of key factors of insulin
      signaling. Thus, our study uncovered a novel metabolic function of hepatic BMAL1
      that promotes de novo lipogenesis via the insulin-mTORC2-AKT signaling during
      refeeding. 

PMID- 25063809
TI  - Multifunctional roles for the protein translocation machinery in RNA anchoring to
      the endoplasmic reticulum.
AB  - Signal sequence-encoding mRNAs undergo translation-dependent localization to the
      endoplasmic reticulum (ER) and at the ER are anchored via translation on Sec61
      bound ribosomes. Recent investigations into the composition and membrane
      association characteristics of ER-associated mRNAs have, however, revealed both
      ribosome-dependent (indirect) and ribosome-independent (direct) modes of mRNA
      association with the ER. These findings raise important questions regarding our
      understanding of how mRNAs are selected, localized, and anchored to the ER. Using
      semi-intact tissue culture cells, we performed a polysome solubilization screen
      and identified conditions that distinguish polysomes engaged in the translation
      of distinct cohorts of mRNAs. To gain insight into the molecular basis of direct
      mRNA anchoring to the ER, we performed RNA-protein UV photocross-linking studies
      in rough microsomes and demonstrate that numerous ER integral membrane proteins
      display RNA binding activity. Quantitative proteomic analyses of HeLa cytosolic
      and ER-bound polysome fractions identified translocon components as selective
      polysome-interacting proteins. Notably, the Sec61 complex was highly enriched in
      polysomes engaged in the translation of endomembrane organelle proteins, whereas
      translocon accessory proteins, such as ribophorin I, were present in all
      subpopulations of ER-associated polysomes. Analyses of the protein composition of
      oligo(dT)-selected UV photocross-linked ER protein-RNA adducts identified
      Sec61alpha,beta and ribophorin I as ER-poly(A) mRNA-binding proteins, suggesting
      unexpected roles for the protein translocation and modification machinery in mRNA
      anchoring to the ER. In summary, we propose that multiple mechanisms of mRNA and
      ribosome association with ER operate to enable an mRNA transcriptome-wide
      function for the ER in protein synthesis. 

PMID- 25063810
TI  - The second sodium site in the dopamine transporter controls cation permeation and
      is regulated by chloride.
AB  - The dopamine transporter (DAT) belongs to the family of neurotransmitter:sodium
      symporters and controls dopamine (DA) homeostasis by mediating Na(+)- and Cl(-)
      dependent reuptake of DA. Here we used two-electrode voltage clamp measurements
      in Xenopus oocytes together with targeted mutagenesis to investigate the
      mechanistic relationship between DAT ion binding sites and transporter
      conductances. In Li(+), DAT displayed a cocaine-sensitive cation leak current ~10
      fold larger than the substrate-induced current in Na(+). Mutation of Na(+)
      coordinating residues in the first (Na1) and second (Na2) binding sites suggested
      that the Li(+) leak depends on Li(+) interaction with Na2 rather than Na1. DA
      caused a marked inhibition of the Li(+) leak, consistent with the ability of the
      substrate to interact with the Li(+)-occupied state of the transporter. The leak
      current in Li(+) was also potently inhibited by low millimolar concentrations of
      Na(+), which according to our mutational data conceivably depended on high
      affinity binding to Na1. The Li(+) leak was further regulated by Cl(-) that most
      likely increases Li(+) permeation by allosterically lowering Na2 affinity.
      Interestingly, mutational lowering of Na2 affinity by substituting Asp-420 with
      asparagine dramatically increased cation permeability in Na(+) to a level higher
      than seen in Li(+). In addition to reveal a functional link between the bound Cl(
      ) and the cation bound in the Na2 site, the data support a key role of Na2 in
      determining cation permeability of the transporter and thereby possibly in
      regulating the opening probability of the inner gate. 

PMID- 25063811
TI  - Regulation of selenocysteine incorporation into the selenium transport protein,
      selenoprotein P.
AB  - Selenoproteins are unique as they contain selenium in their active site in the
      form of the 21st amino acid selenocysteine (Sec), which is encoded by an in-frame
      UGA stop codon. Sec incorporation requires both cis- and trans-acting factors,
      which are known to be sufficient for Sec incorporation in vitro, albeit with low
      efficiency. However, the abundance of the naturally occurring selenoprotein that
      contains 10 Sec residues (SEPP1) suggests that processive and efficient Sec
      incorporation occurs in vivo. Here, we set out to study native SEPP1 synthesis in
      vitro to identify factors that regulate processivity and efficiency. Deletion
      analysis of the long and conserved 3'-UTR has revealed that the incorporation of
      multiple Sec residues is inherently processive requiring only the SECIS elements
      but surprisingly responsive to the selenium concentration. We provide evidence
      that processive Sec incorporation is linked to selenium utilization and that
      reconstitution of known Sec incorporation factors in a wheat germ lysate does not
      permit multiple Sec incorporation events, thus suggesting a role for yet
      unidentified mammalian-specific processes or factors. The relationship between
      our findings and the channeling theory of translational efficiency is discussed. 

PMID- 25063812
TI  - Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long
      term depression at cerebellar parallel fiber-Purkinje cell synapses.
AB  - Cerebellar dysfunction causes ataxia characterized by loss of balance and
      coordination. Until now, the molecular and neuronal mechanisms of several types
      of inherited cerebellar ataxia have not been completely clarified. Here, we
      report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly
      expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to
      an ataxia-like phenotype in mice. Histologically, no obvious morphological
      changes were observed in the cerebellum of Lgr4 mutant mice. However, the number
      of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in
      vitro electrophysiological analysis showed an impaired long term depression (LTD)
      at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently,
      immunostaining experiments showed that the level of phosphorylated cAMP
      responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/
      ) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist,
      rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-)
      cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb
      signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for
      first time an important role for Lgr4 in motor coordination and cerebellar
      synaptic plasticity and provide a potential therapeutic target for certain types
      of inherited cerebellar ataxia. 

PMID- 25063814
TI  - Re: "Postelimination transmission of measles in the US".

PMID- 25063815
TI  - Five authors reply.

PMID- 25063813
TI  - Nitrogen source activates TOR (target of rapamycin) complex 1 via glutamine and
      independently of Gtr/Rag proteins.
AB  - The evolutionary conserved TOR complex 1 (TORC1) activates cell growth in
      response to nutrients. In yeast, TORC1 responds to the nitrogen source via a
      poorly understood mechanism. Leucine, and perhaps other amino acids, activates
      TORC1 via the small GTPases Gtr1 and Gtr2, orthologs of the mammalian Rag
      GTPases. Here we investigate the activation of TORC1 by the nitrogen source and
      how this might be related to TORC1 activation by Gtr/Rag. The quality of the
      nitrogen source, as defined by its ability to promote growth and glutamine
      accumulation, directly correlates with its ability to activate TORC1 as measured
      by Sch9 phosphorylation. Preferred nitrogen sources stimulate rapid, sustained
      Sch9 phosphorylation and glutamine accumulation. Inhibition of glutamine
      synthesis reduces TORC1 activity and growth. Poor nitrogen sources stimulate
      rapid but transient Sch9 phosphorylation. A Gtr1 deficiency prevents the
      transient stimulation of TORC1 but does not affect the sustained TORC1 activity
      in response to good nitrogen sources. These findings suggest that the nitrogen
      source must be converted to glutamine, the preferred nitrogen source in yeast, to
      sustain TORC1 activity. Furthermore, sustained TORC1 activity is independent of
      Gtr/Rag. Thus, the nitrogen source and Gtr/Rag activate TORC1 via different
      mechanisms. 

PMID- 25063816
TI  - Re: "Validation of a method for reconstructing historical rates of smoking
      prevalence".

PMID- 25063817
TI  - Risks of the new EU Data Protection Regulation: an ESMO position paper endorsed
      by the European oncology community.

PMID- 25063819
TI  - Action of the isolated canine diaphragm on the lower ribs at high lung volumes.
AB  - The normal diaphragm has an inspiratory action on the lower ribs, but subjects
      with chronic obstructive pulmonary disease commonly have an inward displacement
      of the lateral portions of the lower rib cage during inspiration. This
      paradoxical displacement, conventionally called 'Hoover's sign', has
      traditionally been attributed to the direct action of radially oriented
      diaphragmatic muscle fibres. In the present study, the inspiratory intercostal
      muscles in all interspaces in anaesthetized dogs were severed so that the
      diaphragm was the only muscle active during inspiration. The displacements of the
      lower ribs along the craniocaudal and laterolateral axes and the changes in
      pleural pressure (?Ppl) and transdiaphragmatic pressure were measured during
      occluded breaths and mechanical ventilation at different lung volumes between
      functional residual capacity (FRC) and total lung capacity. From these data, the
      separate effects on rib displacement of ?Ppl and of the force exerted by the
      diaphragm on the ribs were determined. Isolated spontaneous diaphragm contraction
      at FRC displaced the lower ribs cranially and outward, but this motion was
      progressively reversed into a caudal and inward motion as lung volume increased.
      However, although the force exerted by the diaphragm on the ribs decreased with
      increasing volume, it continued to displace the ribs cranially and outward. These
      observations suggest that Hoover's sign is usually caused by the decrease in the
      zone of apposition and, thus, by the dominant effect of ?Ppl on the lower ribs,
      rather than an inward pull from the diaphragm. 

PMID- 25063820
TI  - Cooperative subunit interactions mediate fast C-type inactivation of hERG1 K+
      channels.
AB  - At depolarized membrane potentials, the conductance of some voltage-gated K(+)
      channels is reduced by C-type inactivation. This gating process is voltage
      independent in Kv1 and involves a conformational change in the selectivity filter
      that is mediated by cooperative subunit interactions. C-type inactivation in
      hERG1 K(+) channels is voltage-dependent, much faster in onset and greatly
      attenuates currents at positive potentials. Here we investigate the potential
      role of subunit interactions in C-type inactivation of hERG1 channels. Point
      mutations in hERG1 known to eliminate (G628C/S631C), inhibit (S620T or S631A) or
      enhance (T618A or M645C) C-type inactivation were introduced into subunits that
      were combined with wild-type subunits to form concatenated tetrameric channels
      with defined subunit composition and stoichiometry. Channels were heterologously
      expressed in Xenopus oocytes and the two-microelectrode voltage clamp was used to
      measure the kinetics and steady-state properties of inactivation of whole cell
      currents. The effect of S631A or T618A mutations on inactivation was a graded
      function of the number of mutant subunits within a concatenated tetramer as
      predicted by a sequential model of cooperative subunit interactions, whereas
      M645C subunits increased the rate of inactivation of concatemers, as predicted
      for subunits that act independently of one another. For mutations located within
      the inactivation gate proper (S620T or G628C/S631C), the presence of a single
      subunit in a concatenated hERG1 tetramer disrupted gating to the same extent as
      that observed for mutant homotetramers. Together, our findings indicate that the
      final step of C-type inactivation of hERG1 channels involves a concerted, all-or
      none cooperative interaction between all four subunits, and that probing the
      mechanisms of channel gating with concatenated heterotypic channels should be
      interpreted with care, as conclusions regarding the nature of subunit
      interactions may depend on the specific mutation used to probe the gating
      process. 

PMID- 25063821
TI  - Glycogen metabolism protects against metabolic insult to preserve carotid body
      function during glucose deprivation.
AB  - The view that the carotid body (CB) type I cells are direct physiological sensors
      of hypoglycaemia is challenged by the finding that the basal sensory neuronal
      outflow from the whole organ is unchanged in response to low glucose. The reason
      for this difference in viewpoint and how the whole CB maintains its metabolic
      integrity when exposed to low glucose is unknown. Here we show that, in the
      intact superfused rat CB, basal sensory neuronal activity was sustained during
      glucose deprivation for 29.1 +/- 1.2 min, before irreversible failure following a
      brief period of excitation. Graded increases in the basal discharge induced by
      reducing the superfusate PO2 led to proportional decreases in the time to the pre
      failure excitation during glucose deprivation which was dependent on a complete
      run-down in glycolysis and a fall in cellular energy status. A similar ability to
      withstand prolonged glucose deprivation was observed in isolated type I cells.
      Electron micrographs and immunofluorescence staining of rat CB sections revealed
      the presence of glycogen granules and the glycogen conversion enzymes glycogen
      synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell
      cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and
      functional depletion of glycogen both significantly reduced the time to
      glycolytic run-down by ~33 and 65%, respectively. These findings suggest that
      type I cell glycogen metabolism allows for the continuation of glycolysis and the
      maintenance of CB sensory neuronal output in periods of restricted glucose
      delivery and this may act as a key protective mechanism for the organ during
      hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus
      account for variation in the reported capacity of the CB to sense physiological
      glucose concentrations and may even underlie its function during pathological
      states associated with augmented CB discharge. 

PMID- 25063822
TI  - Ano1, a Ca2+-activated Cl- channel, coordinates contractility in mouse intestine
      by Ca2+ transient coordination between interstitial cells of Cajal.
AB  - Interstitial cells of Cajal (ICC) are pacemaker cells that generate electrical
      activity to drive contractility in the gastrointestinal tract via ion channels.
      Ano1 (Tmem16a), a Ca(2+)-activated Cl(-) channel, is an ion channel expressed in
      ICC. Genetic deletion of Ano1 in mice resulted in loss of slow waves in smooth
      muscle of small intestine. In this study, we show that Ano1 is required to
      maintain coordinated Ca(2+) transients between myenteric ICC (ICC-MY) of small
      intestine. First, we found spontaneous Ca(2+) transients in ICC-MY in both Ano1
      WT and knockout (KO) mice. However, Ca(2+) transients within the ICC-MY network
      in Ano1 KO mice were uncoordinated, while ICC-MY Ca(2+) transients in Ano1 WT
      mice were rhythmic and coordinated. To confirm the role of Ano1 in the loss of
      Ca(2+) transient coordination, we used pharmacological inhibitors of Ano1
      activity and shRNA-mediated knock down of Ano1 expression in organotypic cultures
      of Ano1 WT small intestine. Coordinated Ca(2+) transients became uncoordinated
      using both these approaches, supporting the conclusion that Ano1 is required to
      maintain coordination/rhythmicity of Ca(2+) transients. We next determined the
      effect on smooth muscle contractility using spatiotemporal maps of contractile
      activity in Ano1 KO and WT tissues. Significantly decreased contractility that
      appeared to be non-rhythmic and uncoordinated was observed in Ano1 KO jejunum. In
      conclusion, Ano1 has a previously unidentified role in the regulation of
      coordinated gastrointestinal smooth muscle function through coordination of
      Ca(2+) transients in ICC-MY.

PMID- 25063823
TI  - Forkhead BoxO transcription factors restrain exercise-induced angiogenesis.
AB  - The physiological process of exercise-induced angiogenesis involves the
      orchestrated upregulation of angiogenic factors together with repression of
      angiostatic factors. The Forkhead Box 'O' (FoxO) transcription factors promote an
      angiostatic environment in pathological contexts. We hypothesized that
      endothelial FoxO1 and FoxO3a also play an integral role in restricting the
      angiogenic response to aerobic exercise training. A single exercise bout
      significantly increased levels of FoxO1 and FoxO3a mRNA (5.5- and 1.7-fold,
      respectively) and protein (1.7- and 2.2-fold, respectively) within the muscles of
      mice 2 h post-exercise compared to sedentary. Training abolished the exercise
      induced increases in both FoxO1 and FoxO3a mRNA and proteins, and resulted in
      significantly lower nuclear levels of FoxO1 and FoxO3a protein (0.5- and 0.4
      fold, respectively, relative to sedentary). Thrombospondin 1 (THBS1) protein
      level closely mirrored the expression pattern of FoxO proteins. The 1.7-fold
      increase in THBS1 protein following acute exercise no longer occurred after 10
      days of repeated exercise. Endothelial cell-directed conditional deletion of
      FoxO1/3a/4 in mice prevented the increase in THBS1 mRNA following a single
      exercise bout. Mice harbouring the endothelial FoxO deletion also demonstrated a
      significant 20% increase in capillary to muscle fibre ratio after only 7 days of
      training while 14 days of training was required to elicit a similar increase in
      wildtype littermates. Our results demonstrate that the downregulation of FoxO1
      and FoxO3a proteins facilitates angiogenesis in response to repeated exercise. In
      conclusion, FoxO proteins can delay exercise-induced angiogenesis, and thus are
      critical regulators of the physiological angiogenic response in skeletal muscle.

PMID- 25063824
TI  - Modulation of spike clustering by NMDA receptors and neurotensin in rat
      supraoptic nucleus neurons.
AB  - Magnocellular neurosecretory cells (MNCs) in the rat supraoptic nucleus display
      clustered firing during hyperosmolality or dehydration. This response is
      beneficial because this type of activity potentiates vasopressin secretion from
      axon terminals in the neurohypophysis and thus promotes homoeostatic water
      reabsorption from the kidney. However, the mechanisms which lead to the
      generation of clustering activity in MNCs remain unknown. Previous work has shown
      that clustered firing can be induced in these neurons through the pharmacological
      activation of NMDA receptors (NMDARs) and that silent pauses observed during this
      activity are mediated by apamin-sensitive calcium activated potassium (SK)
      channels. However, it remains unknown if clustered firing can be induced in situ
      by endogenous glutamate release from axon terminals. Here we show that electrical
      stimulation of glutamatergic osmosensory afferents in the organum vasculosum
      lamina terminalis (OVLT) can promote clustering in MNCs via NMDARs and apamin
      sensitive channels.We also show that the rate of spike clustering induced by NMDA
      varies as a bell-shaped function of voltage, and that partial inhibition of SK
      channels can increase cluster duration and reduce the rate of clustering.
      Finally,we show that MNCs express neurotensin type 2 receptors, and that
      activation of these receptors can simultaneously depolarize MNCs and suppress
      clustered firing induced by bath application of NMDA or by repetitive stimulation
      of glutamate afferents. These studies reveal that spike clustering can be induced
      in MNCs by glutamate release from afferent nerve terminals and that that this
      type of activity can be fine-tuned by neuromodulators such as neurotensin.

PMID- 25063825
TI  - Short-term potentiation of GABAergic synaptic inputs to vasopressin and oxytocin
      neurones.
AB  - The magnocellular vasopressin (VP) and oxytocin (OT) neurones undergo long-term
      synaptic plasticity to accommodate prolonged hormone demand. By contrast, rapidly
      induced,transient synaptic plasticity in response to brief stimuli could enable
      the activation of magnocellular neurones in response to acute challenges. Here,
      we report a robust short-term potentiation of asynchronous GABAergic synaptic
      inputs (STP(GABA)) to VP and OT neurones of the hypothalamic supraoptic nucleus
      elicited by repetitive extracellular electrical stimulation.The STP(GABA)
      required extracellular Ca2+, but did not require activation of glutamate, VP or
      OT receptors or nitric oxide synthesis. Presynaptic action potential generation
      was necessary for the induction, but not the maintenance, of STP(GABA). The
      STP(GABA) led to a minutes-long GABA(A)receptor-dependent increase in spike
      frequency in VP neurones, but not in OT neurones,consistent with an excitatory
      function of GABA in only VP neurones and with the generation of prolonged bursts
      of action potentials in VP neurones. Therefore, this short-term plasticity of
      GABAergic synaptic inputs is likely to play very different roles in the
      regulation of OT and VP neurones and their distinct patterns of physiological
      activation.

PMID- 25063826
TI  - TwHF versus methotrexate in the treatment of rheumatoid arthritis: response to
      Landewe's comment on the TRIFRA study.

PMID- 25063827
TI  - Association between tobacco smoking and response to tumour necrosis factor alpha
      inhibitor treatment in psoriatic arthritis: results from the DANBIO registry.
AB  - OBJECTIVES: To investigate the association between tobacco smoking and disease
      activity, treatment adherence and treatment responses among patients with
      psoriatic arthritis (PsA) initiating the first tumour necrosis factor alpha
      inhibitor therapy (TNFi) in routine care. METHODS: Observational cohort study
      based on the Danish nationwide DANBIO registry. Kaplan-Meier plots, logistic and
      Cox regression analyses by smoking status (current/previous/never smoker) were
      calculated for treatment adherence, ACR20/50/70-responses and EULAR-good
      response. Additional stratified analyses were performed according to gender and
      TNFi-subtype (adalimumab/etanercept/infliximab). RESULTS: Among 1388 PsA patients
      included in the study, 1148 (83%) had known smoking status (33% current, 41%
      never and 26% previous smokers). Median follow-up time was 1.22 years (IQR 0.44
      2.96). At baseline, current smokers had lower Body Mass Index (27 kg/m(2) (23
      30)/28 kg/m(2) (24-31)) (median (IQR)), shorter disease duration (3 years (1-8)/5
      years (2-10)), lower swollen joint count (2 (0-5)/3 (1-6)), higher visual
      analogue-scale (VAS) patient global (72 mm (54-87)/68 mm (50-80)), VAS fatigue
      (72 mm (51-86)/63 mm (40-77)) and Health Assessment Questionnaire (HAQ) score
      (1.1 (0.7 to 1.5)/1.0 (0.5 to 1.5)) than never smokers (all p<0.05). Current
      smokers had shorter treatment adherence than never smokers (1.56 years (0.97 to
      2.15)/2.43 years (1.88 to 2.97), (median (95% CI)), log rank p=0.02) and poorer 6
      months' EULAR-good-response rates (23%/34%), ACR20 (24%/33%) and ACR50 response
      rates (17%/24%) (all p<0.05), most pronounced in men. In current smokers, the
      treatment adherence was poorer for infliximab (HR) 1.62, 95% CI 1.06 to 2.48) and
      etanercept (HR 1.74, 1.14 to 2.66) compared to never smokers, but not for
      adalimumab (HR 0.80, 0.52 to 1.23). CONCLUSION: In PsA, smokers had worse
      baseline patient-reported outcomes, shorter treatment adherence and poorer
      response to TNFi's compared to non-smokers. This was most pronounced in men and
      in patients treated with infliximab or etanercept.

PMID- 25063828
TI  - From global to local: vector-borne disease in an interconnected world.

PMID- 25063829
TI  - E-cigarettes: threat or opportunity?

PMID- 25063830
TI  - Green space and changes in self-rated health among people with chronic illness.
AB  - This prospective study analyses change in self-rated health of chronically ill
      people in relation to green space in their living environment at baseline. Data
      on 1112 people in the Netherlands with one or more medically diagnosed chronic
      disease(s) were used. The percentage of green space was calculated for postal
      code area. Multilevel linear regression analysis was conducted. We found no
      relationship between green space and change in health; however, an unexpected
      relationship between social capital at baseline and health change was discovered.

PMID- 25063831
TI  - Unemployment and dispensed prescribed antidepressants in Stockholm County 1998
      09.
AB  - The association between unemployment rates and population mental health has been
      studied with contradictory results. We examine the association between
      unemployment and antidepressants in Stockholm County. Age- and sex-specific
      monthly data on unemployment and dispensed prescribed antidepressants from
      January 1998 to January 2008 in Stockholm County were used. The association was
      studied with bivariate cointegration analysis with stationarity check of the
      residuals. We found that dispensing of antidepressants was inversely associated
      with unemployment. One interpretation is that antidepressants have not followed
      decreasing unemployment rates. 

PMID- 25063833
TI  - Role of ethylene signalling in the formation of constitutive aerenchyma in
      primary roots of rice.
AB  - Although the extent of aerenchyma (interconnected gas-filled space) formed in the
      cortex of the roots of some species can be promoted by submergence and ethylene,
      such roots also form a somewhat less extensive aerenchyma under well-aerated
      conditions. It has been unclear whether or not ethylene is also involved in
      promoting this constitutive aerenchyma. To confirm the potential of ethylene to
      stimulate aerenchyma development and test the possibility that gas regulates
      constitutive aerenchyma, a novel sandwich method was employed in rice roots. This
      involved germinating japonica rice (Oryza sativa) caryopses sandwiched between
      two agar slabs with or without 1-aminocyclopropane-1-carboxylic acid (ACC) at 1
      uM. The roots were then grown for 4 days in the dark in the presence or absence
      of gaseous 1-methylcyclopropene (1-MCP), an inhibitor of ethylene action.
      Examination of aerenchyma development by light microscopy demonstrated a more
      extensive aerenchyma in cross-section on the ACC-treated side that also commenced
      closer to the root tip. In the presence of 1-MCP at 0.1 or 1 ppm, aerenchyma
      formation was inhibited in the presence or absence of ACC. 1-Methylcyclopropene
      also overcame ACC-inhibited root elongation. The results indicate that ethylene
      signalling is involved in aerenchyma development in primary roots of rice and
      that this may include the regulation of constitutive aerenchyma. In addition,
      root elongation was slowed in control roots in the presence of 1 ppm 1-MCP,
      supporting previous studies demonstrating that endogenous levels of ethylene
      stimulate root elongation. 

PMID- 25063834
TI  - Physiological responses of a halophytic shrub to salt stress by Na2SO4 and NaCl:
      oxidative damage and the role of polyphenols in antioxidant protection.
AB  - Salt stress conditions lead to increased production of reactive oxygen species
      (ROS) in plant cells. Halophytes have the ability to reduce these toxic ROS by
      means of a powerful antioxidant system that includes enzymatic and non-enzymatic
      components. In this research, we used the halophytic shrub Prosopis strombulifera
      to investigate whether the ability of this species to grow under increasing salt
      concentrations and mixtures was related to the synthesis of polyphenolic
      compounds and to the maintenance of leaf pigment contents for an adequate
      photosynthetic activity. Seedlings of P. strombulifera were grown hydroponically
      in Hoagland's solution, gradually adding Na2SO4 and NaCl separately or in
      mixtures until reaching final osmotic potentials of -1, -1.9 and -2.6 MPa.
      Control plants were allowed to develop in Hoagland's solution without salt.
      Oxidative damage in tissues was determined by H2O2 and malondialdehyde content.
      Leaf pigment analysis was performed by high-performance liquid chromatography
      with ultraviolet, and total phenols, total flavonoids, total flavan-3-ols,
      condensed tannins, tartaric acid esters and flavonols were spectrophotometrically
      assayed. Treatment with Na2SO4 increased H2O2 production and lipid peroxidation
      in tissues and induced a sharp increase in flavonoid compounds (mainly flavan-3
      ols) and consequently in the antioxidant activity. Also, Na2SO4 treatment induced
      an increased carotenoid/chlorophyll ratio, which may represent a strategy to
      protect photosystems against photooxidation. NaCl treatment, however, did not
      affect H2O2 content, lipid peroxidation, pigments or polyphenols synthesis. The
      significant accumulation of flavonoids in tissues under Na2SO4 treatment and
      their powerful antioxidant activity indicates a role for these compounds in
      counteracting the oxidative damage induced by severe salt stress, particularly,
      ionic stress. We demonstrate that ionic interactions between different salts in
      salinized soils modify the biochemical and morpho-physiological responses of P.
      strombulifera plants to salinity. 

PMID- 25063835
TI  - Trends in paediatric clinical pharmacology data in US pharmaceutical labelling.
AB  - BACKGROUND: There is often a lack of safety and efficacy data in the paediatric
      population at the time of drug approval. Legislative efforts have promoted
      clinical pharmacology research in this underserved population. We sought to
      determine the quantity and quality of paediatric clinical pharmacology data in US
      drug labelling at the time of initial approval and to evaluate trends over time.
      MATERIALS AND METHODS: The labelling data of 213 new molecular entities approved
      between 2003 and 2012 were systematically reviewed. The type of paediatric
      pharmacology data present at the time of approval was recorded and stratified by
      age group. Labelling revisions were analysed for updated paediatric data. The
      presence of paediatric-specific black-box warnings was noted. RESULTS: Of the 213
      drugs evaluated, 48 had adult-specific indications. Of the remaining 165
      medicines, only 47 (28%) had paediatric study data at the time of initial
      labelling. The number of approved drugs with paediatric data was the greatest in
      2005 (8, 44%) and was at its lowest point in 2012 (3, 11%). Only five medicines
      had neonatal data, with none of the anti-infective agents presenting neonatal
      information. Seven medications had a paediatric-specific black-box warning.
      Additional 16 medicines presented paediatric data during general labelling
      updates. CONCLUSIONS: Despite efforts to improve the quality of paediatric
      clinical pharmacology data, there was not a significant increase in drugs with
      paediatric data at the time of approval over this 10-year study period.
      Paediatric drug approvals and labelling revisions continue to lag behind their
      adult counterparts.

PMID- 25063836
TI  - Nocturnal oxygen saturation profiles of healthy term infants.
AB  - OBJECTIVE: Pulse oximetry is used extensively in hospital and home settings to
      measure arterial oxygen saturation (SpO2). Interpretation of the trend and range
      of SpO2 values observed in infants is currently limited by a lack of reference
      ranges using current devices, and may be augmented by development of cumulative
      frequency (CF) reference-curves. This study aims to provide reference oxygen
      saturation values from a prospective longitudinal cohort of healthy infants.
      DESIGN: Prospective longitudinal cohort study. SETTING: Sleep-laboratory.
      PATIENTS: 34 healthy term infants were enrolled, and studied at 2 weeks, 3, 6, 12
      and 24 months of age (N=30, 25, 27, 26, 20, respectively). INTERVENTIONS: Full
      overnight polysomnography, including 2 s averaging pulse oximetry (Masimo
      Radical). MAIN OUTCOME MEASUREMENTS: Summary SpO2 statistics (mean, median, 5th
      and 10th percentiles) and SpO2 CF plots were calculated for each recording. CF
      reference-curves were then generated for each study age. Analyses were repeated
      with sleep-state stratifications and inclusion of manual artefact removal.
      RESULTS: Median nocturnal SpO2 values ranged between 98% and 99% over the first 2
      years of life and the CF reference-curves shift right by 1% between 2 weeks and 3
      months. CF reference-curves did not change with manual artefact removal during
      sleep and did not vary between rapid eye movement (REM) and non-REM sleep. Manual
      artefact removal did significantly change summary statistics and CF reference
      curves during wake. CONCLUSIONS: SpO2 CF curves provide an intuitive visual tool
      for evaluating whether an individual's nocturnal SpO2 distribution falls within
      the range of healthy age-matched infants, thereby complementing summary
      statistics in the interpretation of extended oximetry recordings in infants.

PMID- 25063837
TI  - Breath-by-breath pulmonary O2 uptake kinetics: effect of data processing on
      confidence in estimating model parameters.
AB  - To improve the signal-to-noise ratio of breath-by-breath pulmonary O2 uptake
      (VO2p) data, it is common practice to perform multiple step transitions, which
      are subsequently processed to yield an ensemble-averaged profile. The effect of
      different data-processing techniques on phase II VO2p kinetic parameter estimates
      (VO2p amplitude, time delay and phase II time constant (tauVO2p)] and model
      confidence [95% confidence interval (CI95)] was examined. Young (n = 9) and older
      men (n = 9) performed four step transitions from a 20 W baseline to a work rate
      corresponding to 90% of their estimated lactate threshold on a cycle ergometer.
      Breath-by-breath VO2p was measured using mass spectrometry and volume turbine.
      Mono-exponential kinetic modelling of phase II VO2p data was performed on data
      processed using the following techniques: (A) raw data (trials time aligned,
      breaths of all trials combined and sorted in time); (B) raw data plus
      interpolation (trials time aligned, combined, sorted and linearly interpolated to
      second by second); (C) raw data plus interpolation plus 5 s bin averaged; (D)
      individual trial interpolation plus ensemble averaged [trials time aligned,
      linearly interpolated to second by second (technique 1; points joined by straight
      line segments), ensemble averaged]; (E) 'D' plus 5 s bin averaged; (F) individual
      trial interpolation plus ensemble averaged [trials time aligned, linearly
      interpolated to second by second (technique 2; points copied until subsequent
      point appears), ensemble averaged]; and (G) 'F' plus 5 s bin averaged. All of the
      model parameters were unaffected by data-processing technique; however, the CI95
      for tauVO2p in condition 'D' (4 s) was lower (P < 0.05) than the CI95 reported
      for all other conditions (5-10 s). Data-processing technique had no effect on
      parameter estimates of the phase II VO2p response. However, the narrowest
      interval for CI95 occurred when individual trials were linearly interpolated and
      ensemble averaged. 

PMID- 25063838
TI  - Alterations in atrial perfusion during atrial fibrillation.
AB  - Left atrial (LA) perfusion during disease states has been a topic of much
      interest, because the clinical implications and detrimental effects of lack of
      blood flow to the atria are numerous. In the chronic setting, changes in
      perfusion may lead to LA ischaemia and structural remodelling, a factor
      implicated in the self-perpetuation of chronic atrial fibrillation (AF). The
      association between AF and altered LA perfusion has been studied, but a direct
      causal association between perfusion changes and AF has not been established. A
      comprehensive literature search of Medline, Embase and Google Scholar databases
      was conducted from 1960 to February 2014. We systematically analysed reference
      lists of physiological articles and reviews for other possibly relevant studies.
      The aim of this review is to provide a comprehensive discussion of the AF
      mediated changes in LA perfusion and the potential mechanisms underlying the
      alterations in coronary flow to the LA in this setting. In addition, we discuss
      the clinical contexts in which changes in LA perfusion may be relevant. Finally,
      this article highlights the need for longitudinal studies of AF that would
      elucidate the changes in LA perfusion resulting from chronic AF and lead to
      advancements in effective treatments to prevent progression of this disease. 

PMID- 25063839
TI  - Increased cardiac output contributes to the development of chronic intermittent
      hypoxia-induced hypertension.
AB  - Chronic intermittent hypoxia (CIH) in animal models has been shown to result in
      hypertension and elevation of sympathetic nervous system activity.
      Sympathetically mediated vasoconstriction is believed to be the primary mechanism
      underpinning CIH-induced hypertension; however, the potential contribution of the
      heart is largely overlooked. We sought to determine the contribution of cardiac
      output (CO) and lumbar sympathetic control of the hindlimb circulation to CIH
      induced hypertension. Male Wistar rats (n = 64) were exposed to 2 weeks of CIH
      [cycles of 90 s hypoxia (5% O2 nadir) and 210 s normoxia] or normoxia for 8 h
      day(-1). Under urethane anaesthesia, CIH-treated animals developed hypertension
      (81.4 +/- 2.2 versus 91.6 +/- 2.4 mmHg; P < 0.001), tachycardia (397 +/- 8 versus
      445 +/- 7 beats min(-1); P < 0.001) and an increased haematocrit (42.4 +/- 0.4
      versus 45.0 +/- 0.4%; P < 0.001). Echocardiography revealed that CIH exposure
      increased the CO [19.3 +/- 1.7 versus 25.8 +/- 2.6 ml min(-1) (100 g)(-1); P =
      0.027] with no change in total peripheral resistance (4.93 +/- 0.49 versus 4.17
      +/- 0.34 mmHg ml(-1) min(-1); P = 0.123). Sympathetic ganglionic blockade
      revealed that sympathetic control over blood pressure was not different (-27.7 +/
      1.6 versus -32.3 +/- 2.9 mmHg; P = 0.095), and no chronic vasoconstriction was
      found in the hindlimb circulation of CIH-treated animals (39.4 +/- 2.5 versus
      38.0 +/- 2.4 MUl min(-1) mmHg(-1); P = 0.336). Lumbar sympathetic control over
      the hindlimb circulation was unchanged in CIH-treated animals (P = 0.761),
      although hindlimb arterial sympathetic density was increased (P = 0.012) and
      vascular sensitivity to phenylephrine was blunted (P = 0.049). We conclude that
      increased CO is sufficient to explain the development of CIH-induced
      hypertension, which may be an early adaptive response to raise O2 flow. We
      propose that sustained elevated cardiac work may ultimately lead to heart
      failure.

PMID- 25063840
TI  - Protein kinase D promotes airway epithelial barrier dysfunction and permeability
      through down-regulation of claudin-1.

PMID- 25063841
TI  - RAP55, a cytoplasmic mRNP component, represses translation in Xenopus oocytes.

PMID- 25063842
TI  - Quantitative transcriptional control of ErbB receptor signaling undergoes graded
      to biphasic response for cell differentiation.

PMID- 25063843
TI  - Does myostatin induce insulin resistance?

PMID- 25063844
TI  - To the reference and beyond: understanding variation in plant genomes.

PMID- 25063845
TI  - Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS)
      assay: implications for improving cancer diagnostics.
AB  - Lymphocyte responses from 208 individuals: 20 with melanoma, 34 with colon
      cancer, and 4 with lung cancer (58), 18 with suspected melanoma, 28 with
      polyposis, and 10 with COPD (56), and 94 healthy volunteers were examined. The
      natural logarithm of the Olive tail moment (OTM) was plotted for exposure to UVA
      through 5 different agar depths (100 cell measurements/depth) and analyzed using
      a repeated measures regression model. Responses of patients with cancer plateaued
      after treatment with different UVA intensities, but returned toward control
      values for healthy volunteers. For precancerous conditions and suspected cancers,
      intermediate responses occurred. ROC analysis of mean log OTMs, for cancers plus
      precancerous/suspect conditions vs. controls, cancer vs. precancerous/suspect
      conditions plus controls, and cancer vs. controls, gave areas under the curve of
      0.87, 0.89, and 0.93, respectively (P<0.001). Optimization allowed test
      sensitivity or specificity to approach 100% with acceptable complementary
      measures. This modified comet assay could represent a stand-alone test or an
      adjunct to other investigative procedures for detecting cancer.

PMID- 25063846
TI  - Toll-like receptor 4 modulates cell migration and cortical neurogenesis after
      focal cerebral ischemia.
AB  - Toll-like receptor 4 (TLR4) mediates brain damage after stroke. Now our objective
      is to determine TLR4 involvement in stroke-induced neurogenesis. Stroke was
      induced by permanent middle cerebral artery occlusion in wild-type and TLR4
      deficient mice. Stereological and densitometric analysis of immunofluorescence
      labeled brain sections and FACS analysis of cell suspensions were performed. Our
      results show that subventricular zone (SVZ) cell proliferation after stroke
      depends on infarct size. Second, when comparing brains with similar lesions, TLR4
      attenuated SVZ proliferation, as shown by a decrease in prominin
      1(+)/EGFR(+)/nestin(-) cells (type-C cells) at 1-2 d, and in BrdU(+) cells at 7
      d, in TLR4(+/+) vs. TLR4(-/-) mice. Interestingly, 7 d after the infarct,
      neuroblasts in TLR4(+/+) mice migrated farther distances, reaching areas closer
      to the lesion than those in TLR4-deficient mice. However, at 14 d, TLR4-deficient
      mice presented a higher number of neuroblasts in all migratory zones than the
      TLR4(+/+) counterparts, which suggests that TLR4 deficiency delays neuroblast
      migration. Consistently, TLR4(+/+) mice showed an increased number of
      interneurons (NeuN(+)/BrdU(+)/GAD67(+) cells) in peri-infarct cortex 14-28 d
      after stroke. Our data indicate that, despite a negative effect on SVZ cell
      proliferation, TLR4 plays an important role in stroke-induced neurogenesis by
      promoting neuroblasts migration and increasing the number of new cortical neurons
      after stroke.

PMID- 25063847
TI  - The light-dark cycle controls peripheral rhythmicity in mice with a genetically
      ablated suprachiasmatic nucleus clock.
AB  - The mammalian circadian timing system consists of a master pacemaker in the
      suprachiasmatic nucleus (SCN), which is thought to synchronize peripheral clocks
      in various organs with each other and with external time. Our knowledge about the
      role of the SCN clock is based mainly on SCN lesion and transplantation studies.
      We have now directly deleted the SCN clock using the Cre/LoxP system and
      investigated how this affects synchronization of peripheral rhythms. Impaired
      locomotor activity and arrhythmic clock gene expression in the SCN confirm that
      the SCN clockwork was efficiently abolished in our mouse model. Nonetheless,
      under light-dark (LD) conditions, peripheral clocks remained rhythmic and
      synchronized to the LD cycle, and phase relationships between peripheral clocks
      were sustained. Adaptation to a shifted LD cycle was accelerated in SCN clock
      deficient mice. Moreover, under zeitgeber-free conditions, rhythmicity of the
      peripheral clock gene expression was initially dampened, and after several days
      peripheral clocks were desynchronized. These findings suggest that the SCN clock
      is dispensable for the synchronization of peripheral clocks to the LD cycle. A
      model describing an SCN clock-independent pathway that synchronizes peripheral
      clocks with the LD cycle is discussed.

PMID- 25063848
TI  - PAAT, a novel ATPase and trans-regulator of mitochondrial ABC transporters, is
      critically involved in the maintenance of mitochondrial homeostasis.
AB  - ATP-binding cassette (ABC) transporters are implicated in a diverse range of
      physiological and pathophysiological processes, such as cholesterol and lipid
      transportation and multidrug resistance. Despite the considerable efforts made in
      understanding of the cellular function of ABC proteins, the regulation mechanism
      of this type of protein is still poorly defined. Here we report the
      identification and functional characterization of a novel ATPase protein, protein
      associated with ABC transporters (PAAT), in humans. PAAT contains a nucleotide
      binding domain (NBD)-like domain and a signal for intramitochondrial sorting. We
      showed that PAAT is localized in both the cytoplasm and the mitochondria and has
      an intrinsic ATPase activity. PAAT physically interacts with the 3 known
      mitochondrial inner membrane ABC proteins, ABCB7, ABCB8, and ABCB10, but not
      ABCB1, ABCB6, or ABCG2, and functionally regulates the transport of ferric
      nutrients and heme biosynthesis. Significantly, PAAT deficiency promotes cell
      death, reduces mitochondrial potential, and sensitizes mitochondria to oxidative
      stress-induced DNA damages. Our experiments revealed that PAAT is a novel ATPase
      and a trans-regulator of mitochondrial ABC transporters that plays an important
      role in the maintenance of mitochondrial homeostasis and cell survival.

PMID- 25063849
TI  - A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor
      heteromer to block signaling and function in vitro and in vivo: effective
      selective antagonism.
AB  - Although the dopamine D1-D2 receptor heteromer has emerging physiological
      relevance and a postulated role in different neuropsychiatric disorders, such as
      drug addiction, depression, and schizophrenia, there is a need for
      pharmacological tools that selectively target such receptor complexes in order to
      analyze their biological and pathophysiological functions. Since no selective
      antagonists for the D1-D2 heteromer are available, serial deletions and point
      mutations were used to precisely identify the amino acids involved in an
      interaction interface between the receptors, residing within the carboxyl tail of
      the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor
      heteromer. It was determined that D1 receptor carboxyl tail residues (404)Glu and
      (405)Glu were critical in mediating the interaction with the D2 receptor.
      Isolated mutation of these residues in the D1 receptor resulted in the loss of
      agonist activation of the calcium signaling pathway mediated through the D1-D2
      receptor heteromer. The physical interaction between the D1 and D2 receptor could
      be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small
      peptide generated from the D1 receptor sequence that contained these amino acids,
      leading to a switch in G-protein affinities and loss of calcium signaling,
      resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2
      heteromer-disrupting peptide in vivo revealed a pathophysiological role for the
      D1-D2 heteromer in the modulation of behavioral despair. This peptide may
      represent a novel pharmacological tool with potential therapeutic benefits in
      depression treatment.

PMID- 25063851
TI  - A superfast muscle in the complex sonic apparatus of Ophidion rochei
      (Ophidiiformes): histological and physiological approaches.
AB  - In teleosts, superfast muscles are generally associated with the swimbladder
      wall, whose vibrations result in sound production. In Ophidion rochei, three
      pairs of muscles were named 'sonic' because their contractions affect swimbladder
      position: the dorsal sonic muscle (DSM), the intermediate sonic muscle (ISM), and
      the ventral sonic muscle (VSM). These muscles were investigated thanks to
      electron microscopy and electromyography in order to determine their function in
      sound production. Fibers of the VSM and DSM were much thinner than the fibers of
      the ISM and epaxial musculature. However, only VSM fibers had the typical
      ultrastructure of superfast muscles: low proportion of myofibrils, and high
      proportions of sarcoplasmic reticulum and mitochondria. In females, each sound
      onset was preceded by the onset of electrical activity in the VSM and the DSM
      (ISM was not tested). The electromyograms of the VSM were very similar to the
      waveforms of the sounds: means for the pulse period were 3.6+/-0.5 and 3.6+/-0.7
      ms, respectively. This shows that the fast VSM (ca. 280 Hz) is responsible for
      the pulse period and fundamental frequency of female sounds. DSM electromyograms
      were generally characterized by one or two main peaks followed by periods of
      lower electrical activity, which suggests a sustained contraction over the course
      of the sound. The fiber morphology of the ISM and its antagonistic position
      relative to the DSM are not indicative of a muscle capable of superfast
      contractions. Overall, this study experimentally shows the complexity of the
      sound production mechanism in the nocturnal fish O. rochei. 

PMID- 25063852
TI  - Two inhibitors of the ubiquitin proteasome system enhance long-term memory
      formation upon olfactory conditioning in the honeybee (Apis mellifera).
AB  - In honeybees (Apis mellifera), the proteasome inhibitor Z-Leu-Leu-Leu-CHO (MG132)
      enhances long-term memory (LTM) formation. Studies in vertebrates using different
      inhibitors of the proteasome demonstrate the opposite, namely an inhibition of
      memory formation. The reason for this contradiction remains unclear. MG132 is an
      inhibitor of the proteasome, but also blocks other proteases. Accordingly, one
      possible explanation might be that other proteases affected by MG132 are
      responsible for the enhancement of LTM formation. We test this hypothesis by
      comparing the effect of MG132 and the more specific proteasome inhibitor clasto
      lactacystin beta-lactone (beta-lactone). We show that these two inhibitors block
      the activity of the proteasome in honeybee brains to a similar extent, do not
      affect the animals' survival but do enhance LTM retention upon olfactory
      conditioning. Thus, the enhancement of LTM formation is not due to MG132-specific
      side effects, but to inhibition of a protease targeted by MG132 and beta-lactone,
      i.e. the proteasome. 

PMID- 25063853
TI  - Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): the links
      between CO2 chemoreception, catecholamines and carbonic anhydrase.
AB  - The ontogeny of carbon dioxide (CO2) sensing in zebrafish (Danio rerio) has not
      been examined. In this study, CO2-mediated increases in heart rate were used to
      gauge the capacity of zebrafish larvae to sense CO2. CO2 is thought to be
      detected via neuroepithelial cells (NECs), which are homologous to mammalian
      carotid body glomus cells. Larvae at 5 days post-fertilization (d.p.f.) exhibited
      tachycardia when exposed for 30 min to 0.75% CO2 (~5.63 mmHg); at 7 d.p.f.,
      tachycardia was elicited by 0.5% CO2 (~3.75 mmHg). Based on pharmacological
      evidence using beta-adrenergic receptor (beta-AR) antagonists, and confirmed by
      beta1-AR translational gene knockdown using morpholinos, the reflex tachycardia
      accompanying hypercapnia was probably mediated by the interaction of
      catecholamines with cardiac beta1 receptors. Because the cardiac response to
      hypercapnia was abolished by the ganglionic blocker hexamethonium, it is probable
      that the reflex cardio-acceleration was mediated by catecholamines derived from
      sympathetic adrenergic neurons. Owing to its likely role in facilitating
      intracellular acidification during exposure to hypercapnia, it was hypothesized
      that carbonic anhydrase (CA) is involved in CO2 sensing, and that inhibition of
      CA activity would blunt the downstream responses. Indeed, the cardiac response to
      hypercapnia (0.75% CO2) was reduced in fish at 5 d.p.f. exposed to acetazolamide,
      a CA inhibitor, and in fish experiencing zCAc (CA2-like a) knockdown. Successful
      knockdown of zCAc was confirmed by CA activity measurements, western blotting and
      immunocytochemistry. Co-injection of embryos with zCAc morpholino and mRNA
      modified at the morpholino binding site restored normal levels of CA activity and
      protein levels, and restored (rescued) the usual cardiac responses to
      hypercapnia. These data, combined with the finding that zCAc is expressed in NECs
      located on the skin, suggest that the afferent limb of the CO2-induced cardiac
      reflex in zebrafish larvae is initiated by coetaneous CO2-sensing neuroepithelial
      cells. 

PMID- 25063854
TI  - A hierarchy of factors influence discontinuous gas exchange in the grasshopper
      Paracinema tricolor (Orthoptera: Acrididae).
AB  - The evolutionary origin and maintenance of discontinuous gas exchange (DGE) in
      tracheate arthropods are poorly understood and highly controversial. We
      investigated prioritization of abiotic factors in the gas exchange control
      cascade by examining oxygen, water and haemolymph pH regulation in the
      grasshopper Paracinema tricolor. Using a full-factorial design, grasshoppers were
      acclimated to hypoxic or hyperoxic (5% O2, 40% O2) gas conditions, or dehydrated
      or hydrated, whereafter their CO2 release was measured under a range of O2 and
      relative humidity (RH) conditions (5%, 21%, 40% O2 and 5%, 60%, 90% RH). DGE was
      significantly less common in grasshoppers acclimated to dehydrating conditions
      compared with the other acclimations (hypoxia, 98%; hyperoxia, 100%; hydrated,
      100%; dehydrated, 67%). Acclimation to dehydrating conditions resulted in a
      significant decrease in haemolymph pH from 7.0+/-0.3 to 6.6+/-0.1 (mean +/- s.d.,
      P=0.018) and also significantly increased the open (O)-phase duration under 5% O2
      treatment conditions (5% O2, 44.1+/-29.3 min; 40% O2, 15.8+/-8.0 min; 5% RH,
      17.8+/-1.3 min; 60% RH, 24.0+/-9.7 min; 90% RH, 20.6+/-8.9 min). The observed
      acidosis could potentially explain the extension of the O-phase under low RH
      conditions, when it would perhaps seem more useful to reduce the O-phase to lower
      respiratory water loss. The results confirm that DGE occurrence and modulation
      are affected by multiple abiotic factors. A hierarchical framework for abiotic
      factors influencing DGE is proposed in which the following stressors are
      prioritized in decreasing order of importance: oxygen supply, CO2 excretion and
      pH modulation, oxidative damage protection and water savings. 

PMID- 25063855
TI  - Scavenging ROS dramatically increase NMDA receptor whole-cell currents in painted
      turtle cortical neurons.
AB  - Oxygen deprivation triggers excitotoxic cell death in mammal neurons through
      excessive calcium loading via over-activation of N-methyl-d-aspartate (NMDA) and
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This
      does not occur in the western painted turtle, which overwinters for months
      without oxygen. Neurological damage is avoided through anoxia-mediated decreases
      in NMDA and AMPA receptor currents that are dependent upon a modest rise in
      intracellular Ca(2+) concentrations ([Ca(2+)]i) originating from mitochondria.
      Anoxia also blocks mitochondrial reactive oxygen species (ROS) generation, which
      is another potential signaling mechanism to regulate glutamate receptors. To
      assess the effects of decreased intracellular [ROS] on NMDA and AMPA receptor
      currents, we scavenged ROS with N-2-mercaptopropionylglycine (MPG) or N
      acetylcysteine (NAC). Unlike anoxia, ROS scavengers increased NMDA receptor whole
      cell currents by 100%, while hydrogen peroxide decreased currents. AMPA receptor
      currents and [Ca(2+)]i concentrations were unaffected by ROS manipulation.
      Because decreases in [ROS] increased NMDA receptor currents, we next asked
      whether mitochondrial Ca(2+) release prevents receptor potentiation during
      anoxia. Normoxic activation of mitochondrial ATP-sensitive potassium (mKATP)
      channels with diazoxide decreased NMDA receptor currents and was unaffected by
      subsequent ROS scavenging. Diazoxide application following ROS scavenging did not
      rescue scavenger-mediated increases in NMDA receptor currents. Fluorescent
      measurement of [Ca(2+)]i and ROS levels demonstrated that [Ca(2+)]i increases
      before ROS decreases. We conclude that decreases in ROS concentration are not
      linked to anoxia-mediated decreases in NMDA/AMPA receptor currents but are rather
      associated with an increase in NMDA receptor currents that is prevented during
      anoxia by mitochondrial Ca(2+) release. 

PMID- 25063856
TI  - Mitochondrial uncoupling as a regulator of life-history trajectories in birds: an
      experimental study in the zebra finch.
AB  - Mitochondria have a fundamental role in the transduction of energy from food into
      ATP. The coupling between food oxidation and ATP production is never perfect, but
      may nevertheless be of evolutionary significance. The 'uncoupling to survive'
      hypothesis suggests that 'mild' mitochondrial uncoupling evolved as a protective
      mechanism against the excessive production of damaging reactive oxygen species
      (ROS). Because resource allocation and ROS production are thought to shape animal
      life histories, alternative life-history trajectories might be driven by
      individual variation in the degree of mitochondrial uncoupling. We tested this
      hypothesis in a small bird species, the zebra finch (Taeniopygia guttata), by
      treating adults with the artificial mitochondrial uncoupler 2,4-dinitrophenol
      (DNP) over a 32-month period. In agreement with our expectations, the uncoupling
      treatment increased metabolic rate. However, we found no evidence that treated
      birds enjoyed lower oxidative stress levels or greater survival rates, in
      contrast to previous results in other taxa. In vitro experiments revealed lower
      sensitivity of ROS production to DNP in mitochondria isolated from skeletal
      muscles of zebra finch than mouse. In addition, we found significant reductions
      in the number of eggs laid and in the inflammatory immune response in treated
      birds. Altogether, our data suggest that the 'uncoupling to survive' hypothesis
      may not be applicable for zebra finches, presumably because of lower effects of
      mitochondrial uncoupling on mitochondrial ROS production in birds than in
      mammals. Nevertheless, mitochondrial uncoupling appeared to be a potential life
      history regulator of traits such as fecundity and immunity at adulthood, even
      with food supplied ad libitum. 

PMID- 25063857
TI  - Host orientation using volatiles in the phoretic nematode Caenorhabditis
      japonica.
AB  - Host orientation is the most important step in host-searching nematodes; however,
      information on direct cues from hosts to evoke this behaviour is limited.
      Caenorhabditis japonica establishes a species-specific phoresy with Parastrachia
      japonensis. Dauer larvae (DL), the non-feeding and phoretic stage of C. japonica,
      are predominantly found on female phoretic hosts, but the mechanisms underlying
      the establishment of this phoresy remain unknown. To determine whether C.
      japonica DL are able to recognize and orient themselves to a host using a
      volatile cue from the host, we developed a Y-tube olfactory assay system in which
      C. japonica DL were significantly attracted to the air from P. japonensis but not
      to the air from three other insects or to CO2. These results demonstrated that C.
      japonica DL utilize volatiles for host recognition and orientation and that the
      presence of a specific volatile kairomone released by the host attracts C.
      japonica DL. 

PMID- 25063858
TI  - Effects of field-realistic doses of glyphosate on honeybee appetitive behaviour.
AB  - Glyphosate (GLY) is a broad-spectrum herbicide used for weed control. The sub
      lethal impact of GLY on non-target organisms such as insect pollinators has not
      yet been evaluated. Apis mellifera is the main pollinator in agricultural
      environments and is a well-known model for behavioural research. Honeybees are
      also accurate biosensors of environmental pollutants and their appetitive
      behavioural response is a suitable tool with which to test sub-lethal effects of
      agrochemicals. We studied the effects of field-realistic doses of GLY on
      honeybees exposed chronically or acutely to the herbicide. We focused on sucrose
      sensitivity, elemental and non-elemental associative olfactory conditioning of
      the proboscis extension response (PER), and foraging-related behaviour. We found
      a reduced sensitivity to sucrose and learning performance for the groups
      chronically exposed to GLY concentrations within the range of recommended doses.
      When olfactory PER conditioning was performed with sucrose reward with the same
      GLY concentrations (acute exposure), elemental learning and short-term memory
      retention decreased significantly compared with controls. Non-elemental
      associative learning was also impaired by an acute exposure to GLY traces.
      Altogether, these results imply that GLY at concentrations found in agro
      ecosystems as a result of standard spraying can reduce sensitivity to nectar
      reward and impair associative learning in honeybees. However, no effect on
      foraging-related behaviour was found. Therefore, we speculate that successful
      forager bees could become a source of constant inflow of nectar with GLY traces
      that could then be distributed among nestmates, stored in the hive and have long
      term negative consequences on colony performance. 

PMID- 25063859
TI  - Effects of body size on the oxygen sensitivity of dragonfly flight.
AB  - One hypothesis for the small size of insects relative to vertebrates, and the
      existence of giant fossil insects, is that atmospheric oxygen levels constrain
      insect body sizes because oxygen delivery is more challenging in larger insects.
      This study tested this hypothesis in dragonflies by measuring the oxygen
      sensitivity of flight metabolic rates and behavior during hovering for 11 species
      of dragonflies that ranged in mass by an order of magnitude. We measured flight
      times and flight metabolic rates in seven oxygen concentrations ranging from 30%
      to 2.5% to assess the sensitivity of their flight to atmospheric oxygen. We also
      assessed the oxygen sensitivity of flight in low-density air (nitrogen replaced
      with helium) in order to increase the metabolic demands of hovering flight.
      Lowered atmospheric densities did induce higher flight metabolic rates. Flight
      behavior was more sensitive to decreasing oxygen levels than flight metabolic
      rate. The oxygen sensitivity of flight metabolic rates and behaviors were not
      correlated with body size, indicating that larger insects are able to maintain an
      oxygen supply-to-demand balance even during flight. 

PMID- 25063860
TI  - Paracellular nutrient absorption is higher in bats than rodents: integrating from
      intact animals to the molecular level.
AB  - Flying vertebrates have been hypothesized to rely heavily on paracellular
      absorption of nutrients to compensate for having smaller intestines than non
      flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and
      two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In
      intact animals, the fractional absorption of orally dosed l-arabinose (Mr 150)
      was 82% in M. lucifugus, which was more than twice that of the rodents.
      Absorption of creatinine (Mr 113) was greater than 50% for all species and did
      not differ between M. lucifugus and the rodents. We also conducted intestinal
      luminal perfusions on anesthetized animals. Absorption of l-arabinose per nominal
      surface area in M. lucifugus was nearly double that of the rodents, while
      absorption of creatinine was not different among species. Using an everted sleeve
      preparation, we demonstrated that high concentrations of l-arabinose and
      creatinine did not inhibit their own uptake, validating their use as passive,
      paracellular probes. Histological measurements indicated that M. lucifugus has
      more cells, and presumably more tight junctions, per nominal surface area than P.
      leucopus. This seems unlikely to explain entirely the higher absorption of l
      arabinose in M. lucifugus during perfusions, because l-arabinose absorption
      normalized to the number of enterocytes was still double that of P. leucopus. As
      an alternative, we investigated tight junction gene expression. M. lucifugus had
      higher expression of claudin-1 and claudin-15, and lower expression of claudin-2
      relative to P. leucopus. Expression of claudin-7 and occludin did not differ
      among species. Taken together, our results support the hypothesis that bats have
      evolved higher paracellular nutrient absorption than non-flying animals, and that
      this phenomenon might be driven by both histological characteristics and
      differences in tight junction gene expression. 

PMID- 25063861
TI  - Parasitic and immune modulation of flight activity in honey bees tracked with
      optical counters.
AB  - Host-parasite interactions are often characterized by changes in the host
      behaviour, which are beneficial to either the parasite or the host, or are a non
      adaptive byproduct of parasitism. These interactions are further complicated in
      animal society because individual fitness is associated with group performance.
      However, a better understanding of host-parasite interaction in animal society
      first requires the identification of individual host behavioural modification.
      Therefore, we challenged honey bee (Apis mellifera) workers with the parasite
      Nosema ceranae or an immune stimulation and tracked their flight activity over
      their lifetime with an optic counter. We found that bees responded differently to
      each stress: both Nosema-infected and immune-challenged bees performed a lower
      number of daily flights compared with control bees, but the duration of their
      flights increased and decreased over time, respectively. Overall, parasitized
      bees spent more time in the field each day than control bees, and the inverse was
      true for immune-challenged bees. Despite the stress of immune challenge, bees had
      a survival similar to that of control bees likely because of their restricted
      activity. We discuss how those different behavioural modifications could be
      adaptive phenotypes. This study provides new insights into how biological stress
      can affect the behaviour of individuals living in society and how host responses
      have evolved. 

PMID- 25063862
TI  - Carbon monoxide regulates the expression of the wound-inducible gene ipomoelin
      through antioxidation and MAPK phosphorylation in sweet potato.
AB  - Carbon monoxide (CO), one of the haem oxygenase (HO) products, plays important
      roles in plant development and stress adaptation. However, the function of CO
      involved in wounding responses is seldom studied. A wound-inducible gene,
      ipomoelin (IPO), of sweet potato (Ipomoea batatas cv. Tainung 57) was used as a
      target to study the regulation of CO in wounding responses. After wounding for
      1h, the endogenous CO content and IbHO expression level were significantly
      reduced in leaves. IPO expression upon wounding was prohibited by the HO
      activator hemin, whereas the HO inhibitor zinc protoporphyrin IX elevated IPO
      expression. The IPO expression induced by wounding, H2O2, or methyl jasmonate was
      inhibited by CO. CO also affected the activities of ascorbate peroxidase,
      catalase, and peroxidase, and largely decreased H2O2 content in leaves. CO
      inhibited the extracellular signal-regulated kinase (ERK) phosphorylation induced
      by wounding. IbMAPK, the ERK of sweet potato, was identified by immunoblotting,
      and the interaction with its upstream activator, IbMEK1, was further confirmed by
      bimolecular fluorescence complementation and co-immunoprecipitation.
      Conclusively, wounding in leaves repressed IbHO expression and CO production,
      induced H2O2 generation and ERK phosphorylation, and then stimulated IPO
      expression.

PMID- 25063863
TI  - Effect of the hope FT-B1 allele on wheat heading time and yield components.
AB  - Precise regulation of flowering time is critical for plant reproductive success
      and, in cereals, to maximize grain yields. Seasonal cues including temperature
      and day length are integrated to regulate the timing of flowering. In temperate
      cereals, extended periods of cold (vernalization) release the repression of
      FLOWERING LOCUS T1 (FT1), which is upregulated in the leaves in response to
      inductive long-day photoperiods. FT1 is a homolog of rice HD3a, which encodes a
      protein transported from leaves to the shoot apical meristem to induce flowering.
      A rare FT-B1 allele from the wheat variety "Hope" has been previously shown to be
      associated with an early flowering phenotype under long-day photoperiods. Here,
      we demonstrate that the Hope FT-B1 allele accelerates flowering even under short
      days, and that it is epistatic to the VERNALIZATION 1 (VRN1) gene. On average,
      the introgression of Hope FT-B1 into 6 genetic backgrounds resulted in 2.6 days
      acceleration of flowering (P<0.0001) and 4.1% increase in spike weight
      (P=0.0093), although in one variety, it was associated with a decrease in spike
      weight. These results suggest that the Hope FT-B1 allele could be useful in wheat
      breeding programs to subtly accelerate floral development and increase adaptation
      to changing environments.

PMID- 25063864
TI  - High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune
      Addison's disease patients.
AB  - The mechanisms behind destruction of the adrenal glands in autoimmune Addison's
      disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an
      intracellular key enzyme of the adrenal cortex, are found in >90% of patients,
      but these autoantibodies are not thought to mediate the disease. In this article,
      we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20
      patients with Addison's disease. Using overlapping 18-aa peptides spanning the
      full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T
      cell responses in a large proportion of Addison's patients both ex vivo and after
      in vitro culture of PBLs <=20 y after diagnosis. In a large proportion of
      patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant
      and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21
      hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase
      positive target cells, consistent with a potential mechanism for disease
      pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase
      often occur in vivo, and that reactive CTLs have substantial proliferative and
      cytolytic potential. These results have implications for earlier diagnosis of
      adrenal failure and ultimately a potential target for therapeutic intervention
      and induction of immunity against adrenal cortex cancer. 

PMID- 25063865
TI  - Leishmania promastigotes induce cytokine secretion in macrophages through the
      degradation of synaptotagmin XI.
AB  - Synaptotagmins (Syts) are type-I membrane proteins that regulate vesicle docking
      and fusion in processes such as exocytosis and phagocytosis. We recently
      discovered that Syt XI is a recycling endosome- and lysosome-associated protein
      that negatively regulates the secretion of TNF and IL-6. In this study, we show
      that Syt XI is directly degraded by the zinc metalloprotease GP63 and excluded
      from Leishmania parasitophorous vacuoles by the promastigotes surface glycolipid
      lipophosphoglycan. Infected macrophages were found to release TNF and IL-6 in a
      GP63-dependent manner. To demonstrate that cytokine release was dependent on GP63
      mediated degradation of Syt XI, small interfering RNA-mediated knockdown of Syt
      XI before infection revealed that the effects of small interfering RNA knockdown
      and GP63 degradation were not cumulative. In mice, i.p. injection of GP63
      expressing parasites led to an increase in TNF and IL-6 secretion and to an
      augmented influx of neutrophils and inflammatory monocytes to the inoculation
      site. Both of these cell types have been shown to be infection targets and aid in
      the establishment of infection. In sum, our data revealed that GP63 induces
      proinflammatory cytokine release and increases infiltration of inflammatory
      phagocytes. This study provides new insight on how Leishmania exploits the immune
      response to establish infection. 

PMID- 25063866
TI  - Two functionally distinct subsets of mast cells discriminated By IL-2-independent
      CD25 activities.
AB  - We identified two mast cell subsets characterized by the differential expression
      of surface CD25 (IL-2Ralpha) and by different abilities to produce cytokines and
      to proliferate, both in vitro and in vivo. CD25 can be expressed on the surface
      of immune cells in the absence of the other chains of the IL-2R, which are
      indispensable for IL-2 signaling. We show that functional differences between the
      two mast cell populations were dependent on CD25 itself, which directly modulated
      proliferation and cytokine responses. These effects were completely independent
      from IL-2 or the expression of the other chains of the high-affinity IL-2R,
      indicating an autonomous and previously unappreciated role for CD25 in regulating
      cell functions. Cells genetically ablated for CD25 completely recapitulated the
      CD25-negative phenotype and never acquired the properties characteristic of CD25
      positive mast cells. Finally, adoptive transfer experiments in the mouse
      demonstrated a different impact of these populations in models of anaphylaxis and
      contact sensitivity. Our findings indicate a general role for CD25 in contexts
      where IL-2 signaling is not involved, and may have important implications for all
      mast cell-related diseases, as well as in all cell types expressing CD25
      independently of its IL-2-related functions. 

PMID- 25063867
TI  - Acute and chronic effects of IL-22 on acetaminophen-induced liver injury.
AB  - Acetaminophen (APAP)-induced liver injury (AILI) accounts for half of the acute
      liver failure cases in the United States. A better understanding of the
      underlying mechanisms of AILI is necessary for the development of novel
      antidotes. We found that pretreatment with IL-22 protected mice from APAP
      mediated hepatotoxicity. The protection was dependent on STAT3, as IL-22 failed
      to reduce APAP hepatotoxicity in liver-specific STAT3 knockout mice. In contrast
      to the acute exposure to IL-22, the endogenous chronic overexpression of IL-22 in
      IL-22 transgenic (TG) mice or IL-22 adenovirus treatment for 6 wk resulted in a
      markedly increased susceptibility to AILI. Furthermore, the hepatic expression
      levels of cytochrome 2E1 (Cyp2E1) and Cyp1A2 were much higher in IL-22TG mice.
      Ablation of Cyp2E1 but not hepatic STAT3 abolished AILI and protein-adduct
      formation in IL-22TG mice. Finally, hepatic expression of HNF-1alpha, a
      transcriptional factor that is known to control Cyp2E1 expression, was elevated
      in IL-22TG mice compared with wild-type mice. Upregulation of hepatic Cyp2E1 was
      only observed in mice with constitutive overexpression of IL-22 but not with
      short-term treatment with one dose of IL-22 or multiple doses of IL-22 for 2 wk.
      In conclusion, short-term acute IL-22 exposure protects mice against AILI through
      STAT3 activation; however, chronic constitutive overexpression of IL-22
      exacerbates AILI by increasing Cyp2E1 and toxic reactive APAP metabolite
      production. These findings may not only enhance our understanding of the effects
      of chronic inflammation on AILI in patients with liver disease, but are also
      helpful to identify novel therapeutic targets for the treatment of AILI. 

PMID- 25063868
TI  - IL-2-inducible T cell kinase tunes T regulatory cell development and is required
      for suppressive function.
AB  - IL-2-inducible T cell kinase (ITK) is a key signaling mediator downstream of TCR,
      mediating T cell positive selection, as well as innate T cell and CD4(+) Th2/Th17
      differentiation. In this article, we show that ITK also negatively tunes IL-2
      induced expansion of conventional Foxp3-expressing regulatory T cells (Tregs). In
      vivo, Treg abundance is inversely correlated with ITK expression, and inducible
      Treg development is inversely dependent on ITK kinase activity. While Treg
      development normally requires both hematopoietic and thymic MHC class 2 (MHC2)
      expression, the absence of ITK allows Treg development with MHC2 expression in
      either compartment, with preference for selection by thymic MHC2, suggesting a
      gatekeeper role for ITK in ensuring that only Tregs selected by both thymic and
      hematopoietic MHC2 survive selection. Although ITK suppresses Treg development
      and is not required for maintenance of neuropilin-1-positive natural Tregs in the
      periphery, it is indispensable for Treg functional suppression of naive CD4(+) T
      cell-induced colitis in Rag(-/-) recipients. ITK thus regulates the development
      and function of Tregs. 

PMID- 25063869
TI  - Rapid remodeling of tight junctions during paracellular diapedesis in a human
      model of the blood-brain barrier.
AB  - Leukocyte transendothelial migration (TEM; diapedesis) is a critical event in
      immune surveillance and inflammation. Most TEM occurs at endothelial cell borders
      (paracellular). However, there is indirect evidence to suggest that, at the tight
      junctions of the blood-brain barrier (BBB), leukocytes migrate directly through
      the endothelial cell body (transcellular). Why leukocytes migrate through the
      endothelial cell body rather than the cell borders is unknown. To test the
      hypothesis that the tightness of endothelial cell junctions influences the
      pathway of diapedesis, we developed an in vitro model of the BBB that possessed
      10-fold higher electrical resistance than standard culture conditions and
      strongly expressed the BBB tight junction proteins claudin-5 and claudin-3. We
      found that paracellular TEM was still the predominant pathway (>=98%) and TEM was
      dependent on PECAM-1 and CD99. We show that endothelial tight junctions
      expressing claudin-5 are dynamic and undergo rapid remodeling during TEM.
      Membrane from the endothelial lateral border recycling compartment is mobilized
      to the exact site of tight junction remodeling. This preserves the endothelial
      barrier by sealing the intercellular gaps with membrane and engaging the
      migrating leukocyte with unligated adhesion molecules (PECAM-1 and CD99) as it
      crosses the cell border. These findings provide new insights into leukocyte
      endothelial interactions at the BBB and suggest that tight junctions are more
      dynamic than previously appreciated. 

PMID- 25063870
TI  - IL-17 suppresses immune effector functions in human papillomavirus-associated
      epithelial hyperplasia.
AB  - Persistent infection with high-risk human papillomaviruses (HPV) causes
      epithelial hyperplasia that can progress to cancer and is thought to depend on
      immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a
      cytokine with diverse functions in host defense and in the pathology of
      autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed
      biopsies from patients with HPV-associated cervical intraepithelial neoplasia
      grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial
      hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression
      of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV
      infected and murine E7-expressing lesions. Using a skin-grafting model, we
      demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective
      host immune responses against the graft. IL-17 was produced by CD3(+) T cells,
      predominantly CD4(+) T cells in human, and CD4(+) and gammadelta T cells in mouse
      hyperplastic lesions. IL-23 and IL-1beta, but not IL-18, induced IL-17 production
      in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive
      role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking
      IL-17 in persistent viral infection may promote antiviral immunity and prevent
      progression to cancer. 

PMID- 25063871
TI  - Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to
      mediate pathogenic autoreactive T cell responses.
AB  - Self-reactive T cells must escape thymic negative selection to mediate pathogenic
      autoimmunity. In the NOD mouse model of autoimmune diabetes, several beta cell
      cytotoxic CD8 T cell populations are known, with the most aggressive of these
      represented by AI4, a T cell clone with promiscuous Ag-recognition
      characteristics. We identified a long-elusive beta cell-specific ligand for AI4
      as an unusually short H-2D(b)-binding 7-mer peptide lacking a C-terminal anchor
      residue and derived from the insulin A chain (InsA14-20). Crystallography reveals
      that compensatory mechanisms permit peptides lacking a C-terminal anchor to bind
      sufficiently to the MHC to enable destructive T cell responses, yet allow cognate
      T cells to avoid negative selection. InsA14-20 shares two solvent-exposed
      residues with previously identified AI4 ligands, providing a structural
      explanation for AI4's promiscuity. Detection of AI4-like T cells, using mimotopes
      of InsA14-20 with improved H-2D(b)-binding characteristics, establishes the AI4
      like T cell population as a consistent feature of the islet infiltrates of NOD
      mice. Our work establishes undersized peptides as previously unrecognized targets
      of autoreactive CD8 T cells and presents a strategy for their further exploration
      as Ags in autoimmune disease. 

PMID- 25063872
TI  - IFN-alpha exerts opposing effects on activation-induced and IL-7-induced
      proliferation of T cells that may impair homeostatic maintenance of CD4+ T cell
      numbers in treated HIV infection.
AB  - To determine whether IFN-alpha is a cause of the T cell hyperactivation and IL-7
      signaling pathway defects that are observed in some HIV patients receiving
      antiretroviral therapy, we have investigated the effect of IFN-alpha on the
      proliferation of CD4(+) and CD8(+) T cells from healthy donors (n = 30) and
      treated HIV(+) donors (n = 20). PBMC were cultured for 7 d with staphylococcal
      enterotoxin B or IL-7 in the absence or presence of 100 U/ml IFN-alpha8. Total
      and naive CD4(+) and CD8(+) T cells were assessed for proliferation (via Ki67
      expression), CD127 expression, and phosphorylated STAT5 levels using flow
      cytometry. IFN-alpha significantly enhanced activation-induced proliferation (via
      staphylococcal enterotoxin B stimulation) but inhibited homeostatic proliferation
      (IL-7 induced) of CD4(+) and CD8(+) T cells. Both of these effects may adversely
      affect CD4(+) T cell homeostasis in HIV patients. CD127 expression was increased
      in both healthy and HIV(+) donors following culture with IFN-alpha8, and levels
      of IL-7-induced phosphorylated STAT5 were increased by IFN-alpha8 in healthy
      donors only. Hence, the inhibitory effects of IFN-alpha on IL-7-induced
      proliferation of CD4(+) T cells are unlikely to be mediated by downregulation of
      CD127 expression or inhibition of STAT5 phosphorylation. These data suggest that
      increased IFN-alpha activity may promote the loss of T cells by accelerating cell
      turnover and activation-induced cell death while decreasing the renewal of T
      cells by inhibiting the proliferative effect of IL-7. 

PMID- 25063873
TI  - Noncanonical NF-kappaB activation mediates STAT3-stimulated IDO upregulation in
      myeloid-derived suppressor cells in breast cancer.
AB  - Immunotherapy for cancer treatment is achieved through the activation of
      competent immune effector cells and the inhibition of immunosuppressive cells,
      such as myeloid-derived suppressor cells (MDSCs). Although MDSCs have been shown
      to contribute to breast cancer development, the mechanism underlying MDSC
      mediated immunosuppression is unclear. We have identified a poorly differentiated
      MDSC subset in breast cancer-suppressing T cell function through STAT3-dependent
      IDO upregulation. In this study we investigated the mechanisms underlying
      aberrant expression of IDO in MDSCs. MDSCs were induced by coculturing human
      CD33(+) myeloid progenitors with MDA-MB-231 breast cancer cells. Increased STAT3
      activation in MDSCs was correlated with activation of the noncanonical NF-kappaB
      pathway, including increased NF-kappaB-inducing kinase (NIK) protein level,
      phosphorylation of cytoplasmic inhibitor of NF-kappaB kinase alpha and p100, and
      RelB-p52 nuclear translocation. Blocking STAT3 activation with the small molecule
      inhibitor JSI-124 significantly inhibited the accumulation of NIK and IDO
      expression in MDSCs. Knockdown of NIK in MDSCs suppressed IDO expression but not
      STAT3 activation. RelB-p52 dimers were found to directly bind to the IDO
      promoter, leading to IDO expression in MDSCs. IL-6 was found to stimulate STAT3
      dependent, NF-kappaB-mediated IDO upregulation in MDSCs. Furthermore, significant
      positive correlation between the numbers of pSTAT3(+) MDSCs, IDO(+) MDSCs, and
      NIK(+) MDSCs was observed in human breast cancers. These results demonstrate a
      STAT3/NF-kappaB/IDO pathway in breast cancer-derived MDSCs, which provides
      insight into understanding immunosuppressive mechanisms of MDSCs in breast
      cancer. 

PMID- 25063874
TI  - Thiamine deficiency promotes T cell infiltration in experimental autoimmune
      encephalomyelitis: the involvement of CCL2.
AB  - Multiple sclerosis (MS) is a complex multifactorial disease that results from the
      interplay between environmental factors and a susceptible genetic background.
      Experimental autoimmune encephalomyelitis (EAE) has been widely used to
      investigate the mechanisms underlying MS pathogenesis. Chemokines, such as CCL2,
      are involved in the development of EAE. We have previously shown that thiamine
      deficiency (TD) induced CCL2 in neurons. We hypothesized that TD may affect the
      pathogenesis of EAE. In this study, EAE was induced in C57BL/6J mice by the
      injection of myelin oligodendroglial glycoprotein (MOG) peptides 35-55 with or
      without TD. TD aggravated the development of EAE, which was indicated by clinical
      scores and pathologic alterations in the spinal cord. TD also accelerated the
      development of EAE in an adoptive transfer EAE model. TD caused microglial
      activation and a drastic increase (up 140%) in leukocyte infiltration in the
      spinal cord of the EAE mice; specifically, TD increased Th1 and Th17 cells. TD
      upregulated the expression of CCL2 and its receptor CCR2 in the spinal cord of
      EAE mice. Cells in peripheral lymph node and spleen isolated from MOG-primed TD
      mice showed much stronger proliferative responses to MOG. CCL2 stimulated the
      proliferation and migration of T lymphocytes in vitro. Our results suggested that
      TD exacerbated the development of EAE through activating CCL2 and inducing
      pathologic inflammation. 

PMID- 25063875
TI  - ADAM9 is a novel product of polymorphonuclear neutrophils: regulation of
      expression and contributions to extracellular matrix protein degradation during
      acute lung injury.
AB  - A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by
      monocytes and macrophages. In this study, we report that ADAM9 is also a product
      of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not
      synthesized de novo by circulating PMNs. Rather, ADAM9 protein is stored in the
      gelatinase and specific granules and the secretory vesicles of human PMNs.
      Unstimulated PMNs express minimal quantities of surface ADAM9, but activation of
      PMNs with degranulating agonists rapidly (within 15 min) increases PMN surface
      ADAM9 levels. Human PMNs produce small quantities of soluble forms of ADAM9.
      Surprisingly, ADAM9 degrades several extracellular matrix (ECM) proteins,
      including fibronectin, entactin, laminin, and insoluble elastin, as potently as
      matrix metalloproteinase-9. However, ADAM9 does not degrade types I, III, or IV
      collagen or denatured collagens in vitro. To determine whether Adam9 regulates
      PMN recruitment or ECM protein turnover during inflammatory responses, we
      compared wild-type and Adam9(-/-) mice in bacterial LPS- and bleomycin-mediated
      acute lung injury (ALI). Adam9 lung levels increase 10-fold during LPS-mediated
      ALI in wild-type mice (due to increases in leukocyte-derived Adam9), but Adam9
      does not regulate lung PMN (or macrophage) counts during ALI. Adam9 increases
      mortality, promotes lung injury, reduces lung compliance, and increases
      degradation of lung elastin during LPS- and/or bleomycin-mediated ALI. Adam9 does
      not regulate collagen accumulation in the bleomycin-treated lung. Thus, ADAM9 is
      expressed in an inducible fashion on PMN surfaces where it degrades some ECM
      proteins, and it promotes alveolar-capillary barrier injury during ALI in mice. 

PMID- 25063876
TI  - IL-2 protects lupus-prone mice from multiple end-organ damage by limiting CD4-CD8
      IL-17-producing T cells.
AB  - IL-2, a cytokine with pleiotropic effects, is critical for immune cell activation
      and peripheral tolerance. Although the therapeutic potential of IL-2 has been
      previously suggested in autoimmune diseases, the mechanisms whereby IL-2
      mitigates autoimmunity and prevents organ damage remain unclear. Using an
      inducible recombinant adeno-associated virus vector, we investigated the effect
      of low systemic levels of IL-2 in lupus-prone MRL/Fas(lpr/lpr) (MRL/lpr) mice.
      Treatment of mice after the onset of disease with IL-2-recombinant adeno
      associated virus resulted in reduced mononuclear cell infiltration and pathology
      of various tissues, including skin, lungs, and kidneys. In parallel, we noted a
      significant decrease of IL-17-producing CD3(+)CD4(-)CD8(-) double-negative T
      cells and an increase in CD4(+)CD25(+)Foxp3(+) immunoregulatory T cells (Treg) in
      the periphery. We also show that IL-2 can drive double-negative (DN) T cell death
      through an indirect mechanism. Notably, targeted delivery of IL-2 to CD122(+)
      cytotoxic lymphocytes effectively reduced the number of DN T cells and
      lymphadenopathy, whereas selective expansion of Treg by IL-2 had no effect on DN
      T cells. Collectively, our data suggest that administration of IL-2 to lupus
      prone mice protects against end-organ damage and suppresses inflammation by
      dually limiting IL-17-producing DN T cells and expanding Treg. 

PMID- 25063879
TI  - Cognitive reappraisal increases neuroendocrine reactivity to acute social stress
      and physical pain.
AB  - Cognitive reappraisal can foster emotion regulation, yet less is known about
      whether cognitive reappraisal alters neuroendocrine stress reactivity. Some
      initial evidence suggests that although long-term training in cognitive
      behavioral therapy techniques (which include reappraisal as a primary training
      component) can reduce cortisol reactivity to stress, some studies also suggest
      that reappraisal is associated with heightened cortisol stress reactivity. To
      address this mixed evidence, the present report describes two experimental
      studies that randomly assigned young adult volunteers to use cognitive
      reappraisal while undergoing laboratory stressors. Relative to the control
      condition, participants in the reappraisal conditions showed greater peak
      cortisol reactivity in response to a socially evaluative speech task (Experiment
      1, N=90) and to a physical pain cold pressor task (Experiment 2, N=94).
      Participants in the cognitive reappraisal group also reported enhanced
      anticipatory psychological appraisals of self-efficacy and control in Experiment
      2 and greater post-stressor self-efficacy. There were no effects of the
      reappraisal manipulation on positive and negative subjective affect, pain, or
      heart rate in either experiment. These findings suggest that although cognitive
      reappraisal fosters psychological perceptions of self-efficacy and control under
      stress, this effortful emotion regulation strategy in the short-term may increase
      cortisol reactivity. Discussion focuses on promising psychological mechanisms for
      these cognitive reappraisal effects. 

PMID- 25063878
TI  - Phosphodiesterase 2A is a major negative regulator of iNOS expression in
      lipopolysaccharide-treated mouse alveolar macrophages.
AB  - PDE2A is a dual-function PDE that is stimulated by cGMP to hydrolyze cAMP
      preferentially. In a two-hit model of ALI, we found previously that PDE2A
      decreased lung cAMP, up-regulated lung iNOS, and exacerbated ALI. Recent data
      suggest that macrophage iNOS expression contributes to ALI but later, promotes
      lung-injury resolution. However, macrophage iNOS is increased by cAMP, suggesting
      that PDE2A could negatively regulate macrophage iNOS expression. To test this, we
      examined the effects of manipulating PDE2A expression and function on LPS-induced
      iNOS expression in a mouse AM cell line (MH-S) and primary mouse AMs. In MH-S
      cells, LPS (100 ng/ml) increased PDE2A expression by 15% at 15 min and 50% at 6 h
      before decreasing at 24 h and 48 h. iNOS expression appeared at 6 h and remained
      increased 48 h post-LPS. Compared with control Ad, Ad.PDE2A-shRNA enhanced LPS
      induced iNOS expression further by fourfold, an effect mimicked by the PDE2A
      inhibitor BAY 60-7550. Adenoviral PDE2A overexpression or treatment with ANP
      decreased LPS-induced iNOS expression. ANP-induced inhibition of iNOS was lost by
      knocking down PDE2A and was not mimicked by 8-pCPT-cGMP, a cGMP analog that does
      not stimulate PDE2A activity. Finally, we found that in primary AMs from LPS
      treated mice, PDE2A knockdown also increased iNOS expression, consistent with the
      MH-S cell data. We conclude that increased AM PDE2A is an important negative
      regulator of macrophage iNOS expression.

PMID- 25063880
TI  - Testosterone responses to competition predict decreased trust ratings of
      emotionally neutral faces.
AB  - A wealth of evidence has linked individual differences in testosterone (T) to
      social, cognitive, and behavioral processes related to human dominance. Moreover,
      recent evidence indicates that a single administration of T reduces interpersonal
      trust in healthy young women. Here, in a sample of men and women (n=96), we
      investigated the extent to which endogenous fluctuations in T during a
      competitive interaction would predict subsequent ratings of trust from
      emotionally neutral faces. Results indicated that a rise in T predicted a
      decrease in trust ratings in men, but not women. These findings provide further
      support for the idea that competition-induced fluctuations in T may serve to
      modulate ongoing and/or future social behavior. 

PMID- 25063877
TI  - Caspase-8 modulates dectin-1 and complement receptor 3-driven IL-1beta production
      in response to beta-glucans and the fungal pathogen, Candida albicans.
AB  - Inflammasomes are central mediators of host defense to a wide range of microbial
      pathogens. The nucleotide-binding domain and leucine-rich repeat containing
      family (NLR), pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in
      triggering caspase-1-dependent IL-1beta maturation and resistance to fungal
      dissemination in Candida albicans infection. beta-Glucans are major components of
      fungal cell walls that trigger IL-1beta secretion in both murine and human immune
      cells. In this study, we sought to determine the contribution of beta-glucans to
      C. albicans-induced inflammasome responses in mouse dendritic cells. We show that
      the NLRP3-apoptosis-associated speck-like protein containing caspase recruitment
      domain protein-caspase-1 inflammasome is absolutely critical for IL-1beta
      production in response to beta-glucans. Interestingly, we also found that both
      complement receptor 3 (CR3) and dectin-1 play a crucial role in coordinating beta
      glucan-induced IL-1beta processing as well as a cell death response. In addition
      to the essential role of caspase-1, we identify an important role for the
      proapoptotic protease caspase-8 in promoting beta-glucan-induced cell death and
      NLRP3 inflammasome-dependent IL-1beta maturation. A strong requirement for CR3
      and caspase-8 also was found for NLRP3-dependent IL-1beta production in response
      to heat-killed C. albicans. Taken together, these results define the importance
      of dectin-1, CR3, and caspase-8, in addition to the canonical NLRP3 inflammasome,
      in mediating beta-glucan- and C. albicans-induced innate responses in dendritic
      cells. Collectively, these findings establish a novel link between beta-glucan
      recognition receptors and the inflammatory proteases caspase-8 and caspase-1 in
      coordinating cytokine secretion and cell death in response to immunostimulatory
      fungal components. 

PMID- 25063881
TI  - Real-time electrocardiogram P-QRS-T detection-delineation algorithm based on
      quality-supported analysis of characteristic templates.
AB  - The main objective of this study is to introduce a simple, low-latency, and
      accurate algorithm for real-time detection of P-QRS-T waves in the
      electrocardiogram (ECG) signal. In the proposed method, real-time signal
      preprocessing, which includes high frequency noise filtering and baseline wander
      reduction, is performed by applying discrete wavelet transform (DWT). A method
      based on signal first-order derivative and adaptive threshold adjustment is
      employed for real-time detection of the QRS complex. Moreover, detection and
      delineation of P- and T-waves are achieved by correlation analysis conducted
      between signal and their templates. Besides, signal quality is investigated
      online, and if the quality of the analysis window is unacceptable, then the
      algorithm will guess (estimate) the locations of P- and T-waves. The operating
      characteristics of the proposed algorithm are evaluated by its implementation to
      an artificially generated ECG signal whose quality is adjustable from the best
      (Quality, 100%) to the worst (Quality, <=40%) cases based on the random-walk
      noise theory. The algorithm was applied to the MIT-BIH arrhythmia database, QT
      database, and Physionet/CinC challenge 2011competition database. The obtained
      results, which were based on the QT database, showed sensitivity and positive
      predictivity of Se=99.63% and P+=99.83%, Se=99.83% and P+=99.98%, and Se=99.74%
      and P+=99.89% for the detection of P-, QRS-, and T-waves, respectively, and the
      obtained results, which were based on the MIT-BIH arrhythmia database, showed
      Se=99.81% and P+=99.70% for the detection of the QRS complex. Moreover, it will
      be shown that the results of the proposed method are reliable for a minimum
      signal quality value of 70%. According to numerical assessments, 8-ms after the
      occurrence of R-wave, its location will be identified by the computer code of the
      proposed algorithm. This parameter is 198-ms and 177-ms for P- and T-waves,
      respectively. 

PMID- 25063882
TI  - Sources of heavy metal pollution in agricultural soils of a rapidly
      industrializing area in the Yangtze Delta of China.
AB  - The rapid industrialization and urbanization in developing countries have
      increased pollution by heavy metals, which is a concern for human health and the
      environment. In this study, 230 surface soil samples (0-20cm) were collected from
      agricultural areas of Jiaxing, a rapidly industrializing area in the Yangtze
      Delta of China. Sequential Gaussian simulation (SGS) and multivariate factorial
      kriging analysis (FKA) were used to identify and explore the sources of heavy
      metal pollution for eight metals (Cu, Zn, Pb, Cr, Ni, Cd, Hg and As). Localized
      hot-spots of pollution were identified for Cu, Zn, Pb, Cr, Ni and Cd with area
      percentages of 0.48 percent, 0.58 percent, 2.84 percent, 2.41 percent, 0.74
      percent, and 0.68 percent, respectively. The areas with Hg pollution covered
      approximately 38 percent whereas no potential pollution risk was found for As.
      The soil parent material and point sources of pollution had significant
      influences on Cr, Ni, Cu, Zn and Cd levels, except for the influence of
      agricultural management practices also accounted for micro-scale variations
      (nugget effect) for Cu and Zn pollution. Short-range (4km) diffusion processes
      had a significant influence on Cu levels, although they did not appear to be the
      dominant sources of Zn and Cd variation. The short-range diffusion pollution
      arising from current and historic industrial emissions and urbanization, and long
      range (33km) variations in soil parent materials and/or diffusion jointly
      determined the current concentrations of soil Pb. The sources of Hg pollution
      risk may be attributed to the atmosphere deposition of industrial emission and
      historical use of Hg-containing pesticides. 

PMID- 25063883
TI  - Effects of nonylphenol and ethinylestradiol on copper redhorse (Moxostoma
      hubbsi), an endangered species.
AB  - The copper redhorse, Moxostoma hubbsi, is an endangered species endemic to
      Quebec. The presence of contaminants, in particular endocrine disrupting
      chemicals (EDCs), in its habitat has been advanced as partly responsible for the
      reproductive difficulties encountered by the species. In the present study,
      immature copper redhorse were exposed to the estrogenic surfactant nonylphenol
      (NP; 1, 10 and 50ug/l) and the synthetic estrogen 17alpha-ethinylestradiol (EE2;
      10ng/l) for 21 days in a flow-through system. The endpoints investigated included
      general health indicators (hepatosomatic index and hematocrit), thyroid hormones,
      sex steroids, brain aromatase activity, plasma and mucus vitellogenin (VTG),
      cytochrome P4501A protein expression and ethoxyresorufin-O-deethylase activity,
      heat shock protein 70 (HSP70) and muscle acetylcholinesterase. Exposure to 10ng
      EE2/l significantly increased brain aromatase activity. Exposure to 50ug NP/l
      resulted in a significant reduction of plasma testosterone concentrations and a
      significant induction of hepatic HSP70 protein expression. NP at 50ug/l also
      induced plasma and mucus VTG. The presence of elevated VTG levels in the surface
      mucus of immature copper redhorse exposed to NP, and its correlation to plasma
      VTG, supports the use of mucus VTG as a non-invasive biomarker to evaluate copper
      redhorse exposure to EDCs in the environment and contribute to restoration
      efforts of the species. The results of the present study indicate that exposure
      to high environmentally relevant concentrations of NP and EE2 can affect
      molecular endpoints related to reproduction in the copper redhorse. 

PMID- 25063884
TI  - Monoclonal antibody targeting chikungunya virus envelope 1 protein inhibits virus
      release.
AB  - Chikungunya virus (CHIKV) causes an acute clinical illness characterized by
      sudden high fever, intense joint pain, and skin rash. Recent outbreaks of
      chikungunya disease in Africa and Asia are a major public health concern;
      however, there is currently no effective licensed vaccine or specific treatment.
      This study reported the development of a mouse monoclonal antibody (MAb), CK47,
      which recognizes domain III within the viral envelope 1 protein and inhibited the
      viral release process, thereby preventing the production of progeny virus. The
      MAb had no effect on virus entry and replication processes. Thus, CK47 may be a
      useful tool for studying the mechanisms underlying CHIKV release and may show
      potential as a therapeutic agent. 

PMID- 25063886
TI  - Effects of elevated dissolved carbon dioxide and perfluorooctane sulfonic acid,
      given singly and in combination, on steroidogenic and biotransformation pathways
      of Atlantic cod.
AB  - In the aquatic environments, the predicted changes in water temperature, pO2 and
      pCO2 could result in hypercapnic and hypoxic conditions for aquatic animals.
      These conditions are thought to affect several basic cellular and physiological
      mechanisms. Yet, possible adverse effects of elevated CO2 (hypercapnia) on
      teleost fish, as well as combined effects with emerging and legacy environmental
      contaminants are poorly investigated. In this study, juvenile Atlantic cod (Gadus
      morhua) were divided into groups and exposed to three different water bath PFOS
      exposure regimes (0 (control), 100 and 200 MUg L(-1)) for 5 days at 1h/day,
      followed by three different CO2-levels (normocapnia, moderate (0.3%) and high
      (0.9%)). The moderate CO2 level is the predicted near future (within year 2300)
      level, while 0.9% represent severe hypercapnia. Tissue samples were collected at
      3, 6 and 9 days after initiated CO2 exposure. Effects on the endocrine and
      biotransformation systems were examined by analyzing levels of sex steroid
      hormones (E2, T, 11-KT) and transcript expression of estrogen responsive genes
      (ERalpha, Vtg-alpha, Vtg-beta, ZP2 and ZP3). In addition, transcripts for genes
      encoding xenobiotic metabolizing enzymes (cyp1a and cyp3a) and hypoxia-inducible
      factor (HIF-1alpha) were analyzed. Hypercapnia alone produced increased levels of
      sex steroid hormones (E2, T, 11-KT) with concomitant mRNA level increase of
      estrogen responsive genes, while PFOS produced weak and time-dependent effects on
      E2-inducible gene transcription. Combined PFOS and hypercapnia exposure produced
      increased effects on sex steroid levels as compared to hypercapnia alone, with
      transcript expression patterns that are indicative of time-dependent interactive
      effects. Exposure to hypercapnia singly or in combination with PFOS produced
      modulations of the biotransformation and hypoxic responses that were apparently
      concentration- and time-dependent. Loading plots of principal component analysis
      (PCA) produced a significant grouping of individual scores according to the
      exposure scenarios at day 6 and 9. Overall, the PCA analysis produced a unique
      clustering of variables that signifies a positive correlation between exposure to
      high PFOS concentration and mRNA expression of E2 responsive genes. Notably, this
      pattern was not evident for individuals exposed to PFOS concentrations in
      combination with elevated CO2 scenarios. To our knowledge, the present study is
      the first of its kind, to evaluate such effects using combined exposure to a
      perfluoroalkyl sulfonate and elevated levels of CO2 saturation, representative of
      future oceanic climate change, in any fish species or lower vertebrate.

PMID- 25063885
TI  - KSHV attachment and entry are dependent on alphaVbeta3 integrin localized to
      specific cell surface microdomains and do not correlate with the presence of
      heparan sulfate.
AB  - Cellular receptors for KSHV attachment and entry were characterized using
      tyramide signal amplification (TSA)-enhanced confocal microscopy. Integrins
      alphaVbeta3, alphaVbeta5 and alpha3beta1 were detected on essentially all the
      actin-based cell surface microdomains that initially bind KSHV, while the
      presence of CD98 and heparan sulfate (HS), the putative attachment receptor, was
      more variable. KSHV bound to the same cell surface microdomains with and without
      HS indicating that initial attachment of KSHV is not dependent on HS and that
      receptors other than HS can mediate attachment. A human salivary gland (HSG)
      epithelial line was identified, which lacks alphaVbeta3 but expresses high levels
      of HS, alpha3beta1 and other putative KSHV receptors. These cells were resistant
      to KSHV binding and infection. Reconstitution of cell surface alphaVbeta3
      rendered HSG cells highly susceptible to KSHV infection, demonstrating a critical
      role for alphaVbeta3 in the binding and entry of KSHV that is not shared with
      other proposed receptors. 

PMID- 25063887
TI  - Additive effects of predator cues and dimethoate on different levels of
      biological organisation in the non-biting midge Chironomus riparius.
AB  - The combined effects of a pesticide and predation risk on sublethal endpoints in
      the midge Chironomus riparius were investigated using a combination of predator
      release kairomones from common carp (Cyprinus carpio) and alarm substances from
      conspecifics together with the pesticide dimethoate. Midge larvae were exposed
      for 30 days to three sublethal dimethoate concentrations (0.01, 0.1 and 0.25 mg
      L(-1)) in the presence or absence of predator cues. Sublethal endpoints were
      analysed at different levels of biological organisation. Available energy
      reserves, enzyme biomarkers, feeding rate and life history endpoints were
      investigated. Three endpoints were significantly affected by the two highest
      dimethoate concentrations, i.e. AChE activity, age at emergence and emergence
      success, with a significant decrease in response after exposure to 0.25, 0.1 and
      0.01 mg L(-1) dimethoate, respectively. Four sublethal endpoints were
      significantly affected by predator stress: Total protein content, GST activity
      and biomass decreased only in the presence of the predation risk, while AChE
      activity further decreased significantly in the presence of predation cues and
      effects on AChE of combined exposure were additive. From this study we can
      conclude that sublethal life history characteristics should be included in
      ecotoxicity testing as well as natural environmental stressors such as predator
      stress, which might act additively with pollutants on fitness related endpoints.

PMID- 25063888
TI  - Phytotoxicity and bioaccumulation of ZnO nanoparticles in Schoenoplectus
      tabernaemontani.
AB  - The rapid development of nanotechnology will inevitably result in an increasing
      release of engineered nanoparticles (NPs) to wastewaters. In this study we
      investigated the fate and toxicity of ZnO NPs in aquatic plant mesocosms, as well
      as the potential for root accumulation and root-to-shoot translocation of these
      Zn NPs in the wetland plant Schoenoplectus tabernaemontani exposed to ZnO NPs.
      The growth of S. tabernaemontani in these hydroponic mesocosms was significantly
      inhibited by ZnO NPs (1000 mg L(-1)) compared to a control. Levels of Zn in the
      plant roots for the ZnO NP treatment ranged from 402 to 36513 MUg g(-1), while
      values ranged from 256 to 9429 MUg g(-)(1) (dry weight) for Zn(2+) treatment,
      implying that the uptake of Zn from ZnO NPs was substantially greater than that
      for Zn(2+). The root uptake (of the initial mass of Zn in the solution) for ZnO
      NP treatment ranged from 8.6% to 43.5%, while for Zn(2+) treatment they were
      1.66% to 17.44%. The low values of the translocation factor for both ZnO NP
      (0.001-0.05) and Zn(2+) (0.05-0.27) treatments implied that the potential for
      translocation of Zn NPs from roots to shoots was limited. ZnO NP distribution in
      the root tissues of S. tabernaemontani was confirmed by scanning electron
      microscopy (SEM). Transmission electron microscopy (TEM) demonstrated that ZnO
      NPs could pass through plant cell walls, and were present within the plant cells
      of S. tabernaemontani.

PMID- 25063889
TI  - [State of the art of surgery. Robotic surgery and telesurgery].

PMID- 25063890
TI  - [Morphometric characteristics of the asterion and the posterolateral surface of
      the skull: its relationship with dural venous sinuses and its neurosurgical
      importance].
AB  - BACKGROUND: The knowledge of the location and morphometric of the lateral venous
      sinus (transverse and sigmoid), and their relationship with the asterion and
      other surface anatomical landmarks, it is imperative for posterolateral
      approaches to the posterior cranial fossa to avoid vascular structures injury and
      surgical complications. OBJECTIVE: Determine an anatomical area security for a
      drill that allows entry into the posterior cranial fossa without damaging
      adjacent structures, and study the morphometric characteristics asterion, the
      lateral sinus and bony landmarks of the posterolateral surface of the skull.
      METHODS: With a 1.3 mm drill drilled both sides of 88 dry skulls (176
      hemicranias). The anatomical landmarks studied were the asterion, the apex of the
      mastoid process, spina suprameatal, the Frankfurt horizontal plane, the posterior
      root of the zygomatic arch, the external occipital protuberance and its
      relationship with the sinus transversus. RESULTS: The asterion type I prevails in
      74.4% of the pieces. In 82.4% of the skulls asterion level is, sinus transversus
      in less than 12.5% and above this at 5.1%. CONCLUSIONS: With the data obtained
      from this and other research, the initial trephine should be placed below the 15
      mm and 15 mm asterion post this to reduce the risk of injury from sinus
      transversus.

PMID- 25063891
TI  - [Microsurgical anatomy importance of A1-anterior communicating artery complex].
AB  - BACKGROUND: The anterior cerebral artery originates from the bifurcation of the
      internal carotid artery lateral to the optic chiasm, then joins with its
      contralateral counterpart via the anterior communicating artery. A1-anterior
      communicating artery complex is the most frequent anatomical variants and is the
      major site of aneurysms between 30 to 37%. OBJECTIVE: Know the anatomy
      microsurgical, variants anatomical and importance of complex precommunicating
      segment-artery anterior communicating in surgery neurological of the pathology
      vascular, mainly aneurysms, in Mexican population. METHODS: The study was
      performed in 30 brains injected. Microanatomy was studied (length and diameter)
      of A1-anterior communicating artery complex and its variants. RESULTS: 60
      segments A1, the average length of left side was 11.35 mm and 11.84 mm was right.
      The average diameter of left was 1.67 mm and the right was 1.64 mm. The average
      number of perforators on the left side was 7.9 and the right side was 7.5.
      Anterior communicating artery was found in 29 brains of the optic chiasm, its
      course depended on the length of the A1 segment. The average length of the
      segment was 2.84 mm, the average diameter was 1.41 mm and the average number of
      perforators was 3.27. A1-anterior communicating artery complex variants were
      found in 18 (60%) and the presence of two blister-like aneurysms. CONCLUSION: It
      is necessary to understand the A1-anterior communicating artery complex
      microanatomy of its variants to have a three-dimensional vision during aneurysm
      surgery.

PMID- 25063892
TI  - [Status of center point thickness and correlation between anatomic and best
      corrected visual acuity changes after photocoagulation, in diabetic macular
      edema].
AB  - BACKGROUND: Center point thickness in diabetic macular edema varies after
      photocoagulation according to its baseline status; it is unknown whether this
      variation reduces the correlation between anatomic and visual acuity changes.
      OBJECTIVE: to identify the contribution of baseline center point thickness to the
      correlation between anatomic and visual acuity after photocoagulation, in eyes
      with diabetic macular edema. METHODS: non-experimental, prospective,
      longitudinal, analytical study in diabetics with macular edema treated with
      photocoagulation, stratified by groups: visual acuity < 0.5 with (group 1) or
      without central thickening (group 2), and visual acuity = 0.5 with (group 3) or
      without central thickening (4). The correlations between changes of center point
      thickness, macular volume, and visual acuity were identified (Spearman). RESULTS:
      79 eyes, 17 in group 1 (21.5%), 21 in group 2 (26.6%), 14 in group 3 (17.7%) and
      27 in group 4 (34.2%). Center point thickness increased in groups 2 and 4, visual
      acuity decreased in group 3 and macular volume in all the groups. The
      correlations between center point thickness and best corrected visual acuity
      changes in group 3, and between macular volume and visual acuity in group 1 were
      negative. The correlations between anatomic variables and visual acuity were low
      in the sample (r= 0.14). CONCLUSION: the increase of center point thickness in
      eyes without baseline central thickening produced opposite correlations between
      groups, which reduced the correlations in the samples. Stratification according
      to baseline center point thickness would make easier to evaluate other variables
      that modify the functional outcome after photocoagulation.

PMID- 25063893
TI  - [Variations in Posner's test for diagnosis of dissociated strabismus].
AB  - BACKGROUND: A particular feature of dissociated strabismus is that the frequency
      of presentation and its magnitude is variable. It is common to find that in
      certain examinations is very obvious, and in others not so much. To facilitate
      exploration some maneuvers are described: Bielchowsky's maneuver, Bielchowsky's
      phenomenon and Posner test. OBJECTIVE: to compare the presence and magnitude of
      the ocular movement in dissociated strabismus in Posner's Test using opaque
      versus translucent occluders. METHODS: Prospective, transversal, descriptive
      study. Patients with diagnosis of were included. Posner's test in two ways: 1)
      With opaque occluders, and 2) with translucent occluders was perforned. RESULTS:
      Ninety-five percent of the patients presented horizontal deviation. Posner's test
      with opaque occluder was positive in all cases (100%). Posner's test with
      translucent occluders was positive in 94% of the patients (p= 8). The magnitude
      of the ocular movement was significantly smaller using translucent occluders than
      opaque occluders. (p= 0.0001). CONCLUSIONS: The Posner's test using opaque
      occluders was more efective to demonstrate clearly and precisely the size of the
      ocular movement in dissociated strabismus.

PMID- 25063894
TI  - [Deep neck abscess. Factors related to reoperation and mortality].
AB  - BACKGROUND: Deep neck abscesses are major complications that arise of
      odontogenic, pharyngeal, or cervicofacial foci, mainly in patients with
      morbidities that facilitate the spread to other spaces. Many of them require
      surgical treatment, and an appropriate evaluation and surgical drainage is
      required to obtain the best results. AIM: To identify factors which relate to
      reoperation and mortality in patient submitted to surgical treatment due to deep
      neck abscess. METHODS: Review of all patients with deep neck abscess who
      underwent surgical treatment in a Head and Neck Surgery Department in a third
      level hospital during a two year period. RESULTS: There were 87 patients, 44 of
      which were female. The median age was 49 years old. Thirty-five patients (40%)
      had comorbidities, diabetes mellitus being the most common, found in 30 (34%)
      patients. Twenty-one patients (24%) required reoperation (primarily due to
      inadequate surgical drainage). The risk factors identified with it were presence
      of comorbidities (mainly diabetes mellitus) (p< 0.05), multiple deep neck spaces
      involvement (p< 0.001) and an ASA score of three or above (p< 0.01). Eight
      patients died, for a mortality of 9%. The factors related to mortality were
      multiple deep neck spaces involvement (p< 0.01), bilateral involvement (p< 0.05)
      and reoperation (p< 0.001). CONCLUSION: Deep neck abscesses appropriate
      evaluation and a complete surgical drainage of all deep space neck abscesses are
      primordial to avoid reoperation and improve survival.

PMID- 25063895
TI  - [Use of the PEEK cage in cervical spondylosis treatment].
AB  - BACKGROUND: Decompression and fusion with autograft is the gold standard
      technique in the treatment of cervical canal strait. Using PEEK cages or boxes of
      non-absorbable polymer with elasticity similar to bone, radiolucent, reduces
      morbidity and same degree of fusion. METHODS: A case series, prospective,
      longitudinal, deliberate intervention, evaluation panel before and after 2 years
      follow-up. Discectomy and PEEK housing placement with autologous graft.
      Arthrodesis were evaluated, cervical lordosis, intervertebral space height, pain
      evaluated with Visual Analogue Scale, Neck Disability Index, operative time,
      intraoperative bleeding, hospital stay and complications. Statistical analysis
      with t Sudent, Wilcoxon and Fisher's exact text. RESULTS: Of 17 patients studied,
      9 (53%) were female. Average age 62 years. The most affected level was C5-6, C6-7
      with 5 patients. Melting was found at 100%. There was no sag or migration of the
      box, space height was conserved, but segmental lordosis was not retained.
      Clinical improvement in all patients as well as disability index was seen.
      Bleeding was on average 187 mL. CONCLUSION: With regard to symptom improvement,
      conservation of interspace height and back, no segmental lordosis conservation
      and fusion using PEEK box is consistent with the literature. We suggest using
      anterior plate to maintain cervical lordosis. We found a melt index of 100%. We
      found clinical improvement of symptoms, pain and disability, and a global loss of
      cervical lordosis.

PMID- 25063896
TI  - [Malignant mesothelioma risk factors: experience in the General Hospital of
      Mexico].
AB  - BACKGROUND: Malignant mesothelioma is a neoplasm of bad prognosis, it is linked
      with asbestos contact, but there are cases without this antecedent. OBJECTIVE: To
      investigate the relationship of asbestos exposition and other factors with
      malignant mesothelioma. METHODS: Retrospective analysis of histologic confirmed
      cases of malignant mesothelioma, neoplasic familiar history, tobacco smoking,
      exposure to wood smoke and to asbestos, were annotated in a paired case/control
      study 1: 1-3 with logistic regression model to identify risk factors for OR.
      RESULTS: 61 cases of malignant mesothelioma were confirmed by histopathologic
      study, 41 male and 20 female. Mean age was 56 years +/- 13 years; 56 cases
      (91.8%) correspond to epithelial malignant mesothelioma, three sarcomatous (4.9%)
      one desmoplastic and one biphasic. One in eight (13.1%) had exposure to asbestos.
      Model of logistic regression with four variables: history of familiar cancer,
      tobacco smoking, wood smoke and asbestos exposition, the the last one with an OR=
      3.083 and p > 0.05. No other variables found to be a risk factor for malignant
      mesothelioma. CONCLUSIONS: Exposure to asbestos is a risk factor for malignant
      mesothelioma, which is confirmed in this study, however it is important to extend
      the investigation of other possible causal factors of this disease.

PMID- 25063897
TI  - [Sleep deprivation effects on cognitive, psychomotor skills and its relationship
      with personal characteristics of resident doctors].
AB  - BACKGROUND: In countries such as United States and European Nations changes have
      been proposed regarding to duty and academic structure of specialists in
      training, this implies adjustments in the norms concerning the number of hours a
      week that residents work. The main argument which has underpinned such
      transformations is based on the assumption that excessive working hours (more
      than 16 hours uninterrupted) cause cognitive and psychomotor disorders in
      residents. OBJECTIVE: To evaluate the association between sleep deprivation and
      cognitive and psychomotor skills of a sample of residents of different
      specialties of Medicine. METHODS: Longitudinal study with measurements pre and
      post shifts, in 31 residents of Medicine. The measured variables were: cognitive
      and psychomotor skills, demographic data and conditions of the shift, quality of
      sleep and psychopathology. RESULTS: 81% residents showed detriment in at least
      one of the tests, however, in psychomotor skills significant different results
      were found in CPR maneuvers between pre and post shift with an improvement in
      scores. CONCLUSIONS: Sleep deprivation causes detriment of cognitive and
      psychomotor skills. While our results can't be generalized, they may constitute a
      precedent for possible changes in the working hours of medical residencies.

PMID- 25063898
TI  - [Carcinosarcoma of the breast a rare entity with fatal prognosis. One case
      report].
AB  - BACKGROUND: breast metaplastic carcinomas are a heterogeneous group of neoplasms
      that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond
      less than 1% of all malignant neoplasms of the mammary gland. They usually
      present as high-grade tumors with a lower rate of lymph node metastases and
      decreased expression of estrogen and progesterone receptors and Her2 and
      increased expression of Her1 and Ki-67. CLINICAL CASE: we report a 52 year old
      woman with a breast carcinosarcoma presented with a left breast tumor fungated,
      ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at
      diagnosis. She received multimodal management with neoadjuvant chemotherapy,
      followed by mastectomy and adjuvant chemotherapy; she presented progression of
      the disease with lung metastases and local massive recurrence, eventually died
      from complications associated to the disease. CONCLUSIONS: metaplastic carcinomas
      of the breast are extremely rare entities. Due the nature of disease and
      presentation, the prognosis is poor in these patients. There are several
      histologic subtypes based on studies of hematoxylin and eosin and
      immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy
      and chemotherapy) for best results.

PMID- 25063899
TI  - [Low grade fibromixoid sarcoma: a purpose of 3 cases and review of the
      bibliography].
AB  - BACKGROUND: Low grade fibromyxoid sarcoma or tumor Evans is a variety of soft
      tissue sarcoma that represents 1% of all malignancies. More common in limbs and
      trunk (50%), we present 3 new cases of retroperitoneal reviewing their
      characteristics and performing a literature review. CLINICAL CASE: In the
      retroperitoneal location highlights the poor specificity of clinical symptoms,
      demonstrating, according to their growth and size, as an abdominal tumor, usually
      painless, or by compression and/or invasion of nearby structures. In cases that
      present the most important finding was the presence of a palpable abdominal tumor
      without other symptoms despite remarkable infiltration of other organs that
      should be included in surgical resection. CONCLUSIONS: We emphasize the
      difficulty of correct diagnosis preoperatively because preoperative studies are
      inconclusive and only the histological and immuno-histo-typing chemistry allow
      precise identification.

PMID- 25063900
TI  - [Perforated duodenal diverticula. Case report and treatment options].
AB  - BACKGROUND: the presence of duodenal diverticula was first described in 1710 by
      Chromel. Duodenal diverticulum is the second most common site of diverticula in
      the digestive tract. Anatomically duodenal diverticula are located in 10 to 67%
      in the second portion of duodenum, and its finding in most cases incidental.
      About 90% of patients appear asymptomatic, manifesting symptoms mostly once
      established complications such as: gastrointestinal bleeding and perforation.
      CLINICAL CASE: 78-years-old woman who attended our Emergency department with
      dyspnea, moderate epigastralgia, abdominal bloating, constipation and difficulty
      to pass gas; Laparotomy was performed to identify duodenal diverticulum in the
      third portion of the duodenum with a perforation of 5 mm in its cupula. It
      proceeds with diverticulectomy. CONCLUSIONS: The diagnosis of duodenal
      diverticulum as a cause of acute abdomen must be considered in our differential
      diagnosis in acute abdomen supported by imaging and endoscopy. The surgical
      management of duodenal diverticulum, in particular the resection of the
      diverticulum, remains as the recommendation for treatment with less morbidity and
      a good recovery.

PMID- 25063901
TI  - [Appendicovesical fistula treated with elective laparoscopic surgery].
AB  - BACKGROUND: appendicovesical fistula is a rare complication of advanced acute
      appendicitis and represents a rare type of enterovesical fistula. Its symptoms
      are vague and imprecise and its diagnosis is difficult, requiring a high level of
      suspicion. Exploratory laparotomy has been the key for diagnosis and definitive
      treatment for many years, but recently the laparoscopic approach is standing out
      among different experienced groups as the method of choice. CLINICAL CASE: we
      report a new case of appendicovesical fistula in a 45 year old female, who was
      remitted from Urology with symptoms of persistent dysuria and pyuria. She was
      finally diagnosed by computerized tomography and the appendicovesical fistula was
      resolved by laparoscopic surgery. This case adds to the one hundred and fifteen
      cases published so far and to the four treated by the laparoscopic approach.
      DISCUSSION: conventional imaging methods are not reliable for the diagnosis of
      enterovesical fistula. Since most appendicovesical fistula are found to be
      secondary to non-diagnosed and advanced acute appendicitis in the majority of the
      consulted publications laparotomy is the key for the diagnosis of apendicovesical
      fistula. However laparoscopy is described as a diagnostic and therapeutic tool in
      few articles. We only found three articles in the literature referring to the
      laparoscopic approach as a therapeutic option. CONCLUSION: computerized
      tomography is the diagnostic method of choice when communication between the
      digestive tract and urinary tract is suspected, particularly if the suspected
      fistula is an appendicovesical one. The laparoscopic approach of an
      appendicovesical fistula is able to confirm the radiological diagnosis and
      provide a definitive treatment.

PMID- 25063902
TI  - [Giant abscessed urachal cyst in adult. Case report].
AB  - BACKGROUND: during gestation, the urachus represents the connection between the
      dome of the bladder and the allantoic duct. This infection occurs preferentially
      in young adults, advocating the haematogenous or lymphatic pathway as possible
      routes of transmission, while a cord or bladder origin may also occur. Urachal
      cysts are rare in adult life, and is observed in only about 2% of adults. CLINIC
      CASE: A 30-year-old male patient with a history of alcoholic hepatitis, diabetes
      mellitus type 2, chronic malnutrition, increased volume beginning with
      generalized abdominal pain, abdominal tumor of 20 by 15 cm, mobile, solid,
      without signs of peritoneal irritation. CT showed the presence of tumor, probably
      bladder-dependent, and apparently cystic. Exploratory laparotomy was found
      infected urachal cyst, draining 3,000 cc purulent material. A partial resection
      of the anterior face, keeping the back by firm adherence to bowel loops was done
      and is evolving satisfactorily. DISCUSSION: urachal abnormalities are rare, with
      male / female ratio of 2 / 1. Although urachal abscess is an infection confined
      to an enclosed space, definitive treatment should not be the simple incision and
      drainage, because of the possibility of malignant transformation of urachal
      remnants. The definitive treatment should be considered complete excision of
      urachal cyst, when the infection is limited. CONCLUSION: the urachus cyst is a
      rare pathology and is a diferencial diagnosis for acute appendicitis and it is
      necessary to know this treatment.

PMID- 25063903
TI  - [Amputation level after frostbite: role of bone scan. A case report].
AB  - BACKGROUND: frostbite is defined as the damage sustained by tissues while subject
      to temperatures below their freezing point. The severity of tissue damage is
      variable, but frequently can result in amputation. Early surgical debridement is
      contraindicated in almost all patients because it can take weeks for definitive
      demarcation of non-viable tissues to occur. Bone scan is indicted in the
      evaluation of frostbite injuries and helps to establish the prognosis early.
      CLINICAL CASE: a 42 year old man suffered frostbite injury in the fingers and
      toes after more than 24 hours at 8,000 meters of altitude. The patient was
      treated with anticoagulant therapy and topical cures for six weeks. During this
      period, we performed two consecutive bone scan studies showing no changes in the
      level of vascularization. However, clinical improvement was important,
      devitalized tissues delimited to the level marked by the bone scan study, so
      amputation was performed. CONCLUSION: Because the bone scan remained invariable,
      we believe that could help us to determine the amputation level early without
      delaying surgery.

PMID- 25063904
TI  - [Guideline for the assessment of clinical research proposals. Comision Nacional
      de Investigacion Cientifica del Instituto Mexicano del Seguro Social].
AB  - BACKGROUND: Medical research is a fundamental tool to achieve the advancement of
      science, through the improvement of strategies aimed to protect, promote and
      restore an individual's and society's health. Three characteristics are required
      to obtain approval of the research proposal: scientific relevance, technical
      quality and the accomplishment of ethical issues. OBJECTIVES: The present review
      aimed at the determination of the specific criteria to perform a critical review
      of research proposals. METHODS: A research was carried out in the PubMed,
      Medline, Ovid and Google Scholar databases, using the terms: peer review,
      research proposals, review and protocols, and reviewers. A total of 3546 related
      articles were reviewed, without finding a guide to critically assess research
      proposals. The guides to assess research articles consider that the quality
      criteria of the study should have been present since the study's conception; many
      of the issues described to review articles are incorporated in the review of the
      research proposals. RESULTS: The specific criteria were integrated to allow the
      reviewer to critically assess research proposals of different areas with
      scientific basis. CONCLUSIONS: The reviewer of research proposals should be
      considered as a professional that contributes to the promotion of knowledge
      advancement through his/her comments, which allow researchers to improve the
      quality of research proposals.

PMID- 25063905
TI  - The effect of drospirenone (3 mg) with ethinyl estradiol (30 mcg) containing
      pills on ovarian blood flows in women with polycystic ovary syndrome: a case
      controlled study.
AB  - OBJECTIVE: To evaluate whether oral contraceptive pill (OCP) therapy has any
      effects on ovarian stromal blood flow by using pulsed and color Doppler at the
      end of 3 months follow-up period of OCP-users and non-users with or without
      polycystic ovary syndrome (PCOS). STUDY DESIGN: 200 patients were included in the
      study. The patients were designed into four groups as follows; Group 1: PCOS
      patients that received OCP containing 30 mcg ethinyl estradiol (EE) plus 3mg
      drospirenone for 3 months (DRP n=50); Group 2: PCOS patients that received no
      medication (n=50); Group 3: Healthy controls that received OCP (EE plus DRP)
      (n=50); Group 4: healthy controls that received no medication (n=50). Resistance
      index (RI) and pulsatility index (PI) of both ovarian arteries, hormonal,
      anthropometric and biochemical parameters were assessed before and after 3
      months. RESULTS: There was a significant increament in RI and PI of both ovarian
      arteries in healthy controls (Group 3) and in women with PCOS (Group 1) who
      received OCP (p<0.001). The increment rate in both Doppler parameters were
      significantly higher in women with PCOS (Group 1) than healthy controls (Group 3)
      (p<0.001). Whereas RI and PI values of both ovaries remained unchanged in all
      untreated women with or without PCOS (Groups 2 and 4). CONCLUSION: OCP therapy
      reduced ovarian vascularization in both PCOS and healthy users after 3 months of
      therapy and this decrease is especially noticeable in women with PCOS.

PMID- 25063906
TI  - Visual and auditory perception in preschool children at risk for dyslexia.
AB  - Recently, there has been renewed interest in perceptive problems of dyslexics. A
      polemic research issue in this area has been the nature of the perception
      deficit. Another issue is the causal role of this deficit in dyslexia. Most
      studies have been carried out in adult and child literates; consequently, the
      observed deficits may be the result rather than the cause of dyslexia. This study
      addresses these issues by examining visual and auditory perception in children at
      risk for dyslexia. We compared children from preschool with and without risk for
      dyslexia in auditory and visual temporal order judgment tasks and same-different
      discrimination tasks. Identical visual and auditory, linguistic and nonlinguistic
      stimuli were presented in both tasks. The results revealed that the visual as
      well as the auditory perception of children at risk for dyslexia is impaired. The
      comparison between groups in auditory and visual perception shows that the
      achievement of children at risk was lower than children without risk for dyslexia
      in the temporal tasks. There were no differences between groups in auditory
      discrimination tasks. The difficulties of children at risk in visual and auditory
      perceptive processing affected both linguistic and nonlinguistic stimuli. Our
      conclusions are that children at risk for dyslexia show auditory and visual
      perceptive deficits for linguistic and nonlinguistic stimuli. The auditory
      impairment may be explained by temporal processing problems and these problems
      are more serious for processing language than for processing other auditory
      stimuli. These visual and auditory perceptive deficits are not the consequence of
      failing to learn to read, thus, these findings support the theory of temporal
      processing deficit. 

PMID- 25063907
TI  - The genetics of host-virus coevolution in invertebrates.
AB  - Although viral infection and antiviral defence are ubiquitous, genetic data are
      currently unavailable from the vast majority of animal phyla-potentially biasing
      our overall perspective of the coevolutionary process. Rapid adaptive evolution
      is seen in some insect antiviral genes, consistent with invertebrate-virus 'arms
      race' coevolution, but equivalent signatures of selection are hard to detect in
      viruses. We find that, despite the large differences in vertebrate, invertebrate,
      and plant immune responses, comparison of viral evolution fails to identify any
      difference among these hosts in the impact of positive selection. The best
      evidence for invertebrate-virus coevolution is currently provided by large-effect
      polymorphisms for host resistance and/or viral evasion, as these often appear to
      have arisen and spread recently, and can be favoured by virus-mediated selection.

PMID- 25063909
TI  - Two structurally analogous ruthenium complexes as naked-eye and reversible
      molecular "light switch" for G-quadruplex DNA.
AB  - A pair of symmetrical furyl based ruthenium(II) complexes ([Ru(phen)2dpq-df](2+)
      (1) and [Ru(bpy)2dpq-df](2+) (2) (phen=1,10-phenanthroline, bpy=2,2'-bipyridine,
      dpq-df=dipyrido (3,2-a:2',3'-c) quinoxaline-difuran) have been prepared and
      characterized. The binding properties of both complexes toward G-quadruplex DNA
      have been investigated by fluorescence spectroscopy, UV-Vis spectroscopy,
      circular dichroism (CD), fluorescence resonance energy transfer (FRET) melting
      assays and molecular docking studies. The experimental results indicated that
      both Ru-complexes exhibited a remarkable "light switch" effect in the presence of
      hybrid G-quadruplex DNA. Interestingly, the "light switch" can be repeated off
      and on through the successive addition of Cu(2+) ions and EDTA, and all these
      behaviors can be observed even by the naked eyes. Moreover, FRET melting assay
      revealed that both complexes could be potential stabilizers for G-quadruplex
      architectures. The computational studies not only confirmed that the two complex
      molecules bound to one G-quadruplex DNA molecule, but also explained the "light
      switch" effect. 

PMID- 25063908
TI  - Regional variation in colorectal cancer testing and geographic availability of
      care in a publicly insured population.
AB  - Despite its demonstrated effectiveness, colorectal cancer (CRC) testing is
      suboptimal, particularly in vulnerable populations such as those who are publicly
      insured. Prior studies provide an incomplete picture of the importance of the
      intersection of multilevel factors affecting CRC testing across heterogeneous
      geographic regions where vulnerable populations live. We examined CRC testing
      across regions of North Carolina by using population-based Medicare and Medicaid
      claims data from disabled individuals who turned 50 years of age during 2003
      2008. We estimated multilevel models to examine predictors of CRC testing,
      including distance to the nearest endoscopy facility, county-level endoscopy
      procedural rates, and demographic and community contextual factors. Less than 50%
      of eligible individuals had evidence of CRC testing; men, African-Americans,
      Medicaid beneficiaries, and those living furthest away from endoscopy facilities
      had significantly lower odds of CRC testing, with significant regional variation.
      These results can help prioritize intervention strategies to improve CRC testing
      among publicly insured, disabled populations. 

PMID- 25063910
TI  - Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato ligands.
AB  - We report new anticancer prodrugs, platinum(IV) derivatives of oxaliplatin
      conjugated with valproic acid (VPA), a well-known drug having histone deacetylase
      inhibitory activity. Like most platinum(IV) derivatives, the cytotoxicity of the
      conjugates was lower in cell culture than that of oxaliplatin, but greater than
      those of its Pt(IV) derivative containing biologically inactive axial ligands in
      several cancer cell lines. Notably, these conjugates display activity in both
      cisplatin sensitive- and resistant tumor cells capable of both markedly enhanced
      accumulation in tumor cells and acting in a dual threat manner, concurrently
      targeting histone deacetylase and genomic DNA. These results demonstrate the dual
      targeting strategy to be a valuable route to pursue in the design of platinum
      agents which may be more effective in cancer types that are typically resistant
      to therapy by conventional cisplatin. Moreover, platinum(IV) derivatives
      containing VPA axial ligands seem to be promising dual-targeting candidates for
      additional preclinical studies. 

PMID- 25063911
TI  - Cyclopalladated and cycloplatinated benzophenone imines: antitumor, antibacterial
      and antioxidant activities, DNA interaction and cathepsin B inhibition.
AB  - The antitumor, antibacterial and antioxidant activity, DNA interaction and
      cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds
      [Pd(C,N)]2(MU-X)2 [X=OAc (1), X=Cl (2)] and trans-N,P-[M(C,N)X(PPh3)] [M=Pd,
      X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho
      metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated
      towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines
      and that of compounds 1-4 towards the HCT-116 human colon cancer cell line. These
      cytotoxicities have been compared with those previously reported for compounds 1
      4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were
      approximately four times more active than cisplatin against the MDA-MB-231 and
      MCF-7 cancer cell lines, and compound 5, was approximately four times more potent
      than cisplatin against the HCT-116 cancer cell line. The antibacterial activity
      of compounds 1-5 was in between the ranges of activity of the commercial
      antibiotic compounds cefixime and roxithromycin. Complexes 1-2 and 4-5 presented
      also antioxidant activity. Compounds 1-5 alter the DNA tertiary structure in a
      similar way to cisplatin, but at higher concentration, and do not present a high
      efficiency as cathepsin B inhibitors. Compound 5 has not been previously
      described, and its preparation, characterization, and X-ray crystal structure are
      reported. 

PMID- 25063912
TI  - Explaining PAH desorption from sediments using Rock Eval analysis.
AB  - Here, we provide Rock Eval and black carbon (BC) characteristics and polycyclic
      aromatic hydrocarbon (PAH) distribution coefficients (KD) for sediments from the
      Danube, Elbe, Ebro, and Meuse river basins. PAH desorption kinetic parameters
      were determined using sequential Tenax extractions. We show that residual carbon
      (RC) from Rock Eval analysis is an adequate predictor of fast, slow, and very
      slow desorbing fractions of 4-ring PAHs. RC correlated better than BC, the latter
      constituting only 7% of RC. A dual domain sorption model was statistically
      superior to a single domain model in explaining KD for low molecular weight PAHs,
      whereas the opposite was observed for high molecular weight PAHs. Because
      particularly the 4-ring PAHs are bioavailable and relevant from a risk assessment
      perspective and because their fast desorbing fractions correlate best with RC, we
      recommend RC as a relevant characteristic for river sediments. 

PMID- 25063913
TI  - Organophosphate flame retardants and organosiloxanes in predatory freshwater fish
      from locations across Canada.
AB  - Whole body homogenates of Lake Trout (Salvelinus namaycush) or Walleye (Sander
      vitreus) collected from Canadian lakes were screened for organophosphate flame
      retardant (OPFR) and organosiloxane compounds. Six OPFR and five siloxane
      compounds were detected above quantitation limits in at least one individual fish
      from sampled lakes. The OPFRs, tris(2-chloroethyl) phosphate (TCEP) and tris(2
      butoxyethyl) phosphate (TBOEP), were most frequently quantified with
      concentrations ranging from <0.07 to 9.8 ng/g (ww). Levels of TBOEP were highest
      in fish from the Great Lakes region while TCEP was detected only in fish from the
      northernmost lakes in our network. Concentrations of the cyclic siloxanes,
      octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and
      dodecamethylcyclohexasiloxane (D6), were above quantitation limits in all fish.
      D5 was the most abundant siloxane across all sampling locations with the highest
      concentrations (45-719 ng/g ww) observed in Lake Trout from the western end of
      Lake Ontario near the mouth of the Niagara River. 

PMID- 25063914
TI  - Estimating terrestrial amphibian pesticide body burden through dermal exposure.
AB  - Dermal exposure presents a potentially significant but understudied route for
      pesticide uptake in terrestrial amphibians. Our study measured dermal uptake of
      pesticides of varying hydrophobicity (logKow) in frogs. Amphibians were
      indirectly exposed to one of five pesticide active ingredients through contact
      with contaminated soil: imidacloprid (logKow = 0.57), atrazine (logKow = 2.5),
      triadimefon (logKow = 3.0), fipronil (logKow = 4.11) or pendimethalin (logKow =
      5.18). All amphibians had measurable body burdens at the end of the exposure in
      concentrations ranging from 0.019 to 14.562 MUg/g across the pesticides tested.
      Atrazine produced the greatest body burdens and bioconcentration factors, but
      fipronil was more permeable to amphibian skin when application rate was
      considered. Soil partition coefficient and water solubility were much better
      predictors of pesticide body burden, bioconcentration factor, and skin
      permeability than logKow. Dermal uptake data can be used to improve risk
      estimates of pesticide exposure among amphibians as non-target organisms. 

PMID- 25063915
TI  - Experimental field studies with non-human primates.
AB  - One way to study language evolution is to compare human communication with
      closely related non-human primate species. This comparative approach has turned
      to be especially productive if subjects are studied under natural field
      conditions in which they have evolved. Various observation techniques have been
      developed, but field experiments are often needed to clarify underlying cause
      effect relations. Here, I review the main experimental designs that are suitable
      for primate fieldwork and discuss some scientific advancements that they have
      generated. Field experiments are notoriously difficult to carry out for a range
      of reasons that are discussed. Nonetheless, considerable progress has been made
      in recent years, including with great apes, which have traditionally been
      neglected in experimental research in the wild. 

PMID- 25063916
TI  - The option to abandon: stimulating innovative groundwater remediation
      technologies characterized by technological uncertainty.
AB  - Many studies on technology adoption demonstrate that uncertainty leads to a
      postponement of investments by integrating a wait option in the economic
      analysis. The aim of this study however is to demonstrate how the investment in
      new technologies can be stimulated by integrating an option to abandon.
      Furthermore, this real option analysis not only considers the ex ante decision
      analysis of the investment in a new technology under uncertainty, but also allows
      for an ex post evaluation of the investment. Based on a case study regarding the
      adoption of an innovative groundwater remediation strategy, it is demonstrated
      that when the option to abandon the innovative technology is taken into account,
      the decision maker decides to invest in this technology, while at the same time
      it determines an optimal timing to abandon the technology if its operation proves
      to be inefficient. To reduce uncertainty about the effectiveness of groundwater
      remediation technologies, samples are taken. Our analysis shows that when the
      initial belief in an effective innovative technology is low, it is important that
      these samples provide correct information in order to justify the adoption of the
      innovative technology. 

PMID- 25063917
TI  - Pleistocene paleo-groundwater as a pristine fresh water resource in southern
      Germany--evidence from stable and radiogenic isotopes.
AB  - Shallow groundwater aquifers are often influenced by anthropogenic contaminants
      or increased nutrient levels. In contrast, deeper aquifers hold potentially
      pristine paleo-waters that are not influenced by modern recharge. They thus
      represent important water resources, but their recharge history is often unknown.
      In this study groundwater from two aquifers in southern Germany were analyzed for
      their hydrogen and oxygen stable isotope compositions. One sampling campaign
      targeted the upper aquifer that is actively recharged by modern precipitation,
      whereas the second campaign sampled the confined, deep Benkersandstein aquifer.
      The groundwater samples from both aquifers were compared to the local meteoric
      water line to investigate sources and conditions of groundwater recharge. In
      addition, the deep groundwater was dated by tritium and radiocarbon analyses.
      Stable and radiogenic isotope data indicate that the deep-aquifer groundwater was
      not part of the hydrological water cycle in the recent human history. The results
      show that the groundwater is older than ~20,000 years and most likely originates
      from isotopically depleted melt waters of the Pleistocene ice age. Today, the use
      of this aquifer is strictly regulated to preserve the pristine water. Clear
      identification of such non-renewable paleo-waters by means of isotope
      geochemistry will help local water authorities to enact and justify measures for
      conservation of these valuable resources for future generations in the context of
      a sustainable water management.

PMID- 25063918
TI  - Prophylactic effects of prostaglandin E2 on NSAID-induced enteropathy-role of EP4
      receptors in its protective and healing-promoting effects.
AB  - Prostaglandin E2 not only prevents NSAID-generated small intestinal lesions, but
      also promotes their healing. The protective effects of prostaglandin E2 are
      mediated by the activation of EP4 receptors and functionally associated with the
      stimulation of mucus/fluid secretions and inhibition of intestinal hypermotility,
      resulting in the suppression of enterobacterial invasion and iNOS up-regulation,
      which consequently prevents intestinal lesions. Prostaglandin E2 also promotes
      the healing of intestinal damage by stimulating angiogenesis through the up
      regulation of VEGF expression via the activation of EP4 receptors. These findings
      have contributed to a further understanding of the mechanisms responsible for
      'protective' and 'healing-promoting' effects of prostaglandin E2 and the
      development of new strategies for the prophylactic treatment of NSAID-induced
      enteropathy. 

PMID- 25063920
TI  - Highly sensitive fluorescence detection of target DNA by coupling exonuclease
      assisted cascade target recycling and DNAzyme amplification.
AB  - Because of the intrinsic importance of nucleic acid as bio-targets, the simple
      and sensitive detection of nucleic acid is very essential for biological studies
      and medical diagnostics. Herein, a simple, isothermal and highly sensitive
      fluorescence detection of target DNA was developed with the combination of
      exonuclease III (Exo III)-assisted cascade target recycling and DNAzyme
      amplification. A hairpin DNA probe was designed, which contained the 3'
      protruding DNA fragment as target recognition unit, the caged DNA fragment in the
      stem region as target analogue, and the caged 8-17 DNAzyme sequence in the loop
      region as signal response unit. Upon sensing of target DNA, the 3'-strand of
      hairpin DNA probe could be stepwise removed by Exo III, accompanied by the
      releasing of target DNA and autonomous generation of new target analogues for the
      successive hybridization and cleavage process. Simultaneously, the 8-17 DNAzyme
      unit could be exponentially released from this hairpin DNA probe and activated
      for the cyclic cleavage toward the ribonucleotide-containing molecular beacon
      substrate, inducing a remarkable fluorescence signal amplification for target
      detection. A low detection limit of 20 fM with an excellent selectivity toward
      target DNA could be achieved. The developed cascade amplification strategy may be
      further extended for the detection of a wide spectrum of analytes including
      protein and biological small molecules by combining DNA aptamer technology.

PMID- 25063919
TI  - RNA-binding proteins and microRNAs in gastrointestinal epithelial homeostasis and
      diseases.
AB  - The epithelium of gastrointestinal (GI) mucosa is a rapidly self-renewing tissue
      in the body, and its homeostasis is preserved through strict regulation of cell
      proliferation and apoptosis. Epithelial cells originate from a small number of
      pluripotent stem cells, which divide to either renew themselves or become
      committed crypt cells. RNA-binding proteins (RBPs) and microRNAs (miRNAs)
      regulate gene expression at the posttranscriptional level and are recently shown
      to modulate GI mucosal growth and repair after injury. Here we highlight the
      roles of RBPs HuR, CUG-binding protein 1, AU-binding factor 1, and several GI
      epithelial-specific miRNAs in gut mucosal homeostasis and diseases and also
      further analyze the mechanisms through which RBPs and miRNAs modulate the
      stability and translation of target mRNAs. 

PMID- 25063921
TI  - Assay of multiplex proteins from cell metabolism based on tunable aptamer and
      microchip electrophoresis.
AB  - A simple and rapid method for multiplex protein assay based on tunable aptamer by
      microchip electrophoresis has been developed. Different lengths of aptamers can
      modulate the electrophoretic mobility of proteins, allowing the protein molecules
      to be effectively separated in hydroxyethyl cellulose buffer with 1.00 mM
      magnesium ion. A non-specific DNA was exploited as an internal standard to
      achieve the quantitative assay and to reduce the interference. A fluorescence dye
      SYBR gold was exploited to improve the sensitivity and to suppress the
      interference from sample matrix. Under optimum conditions, quantitative assay of
      PDGF-BB (R(2)=0.9986), VEGF165 (R(2)=0.9909), and thrombin (R(2)=0.9947) were
      achieved with a dynamic range in the 5.00-150.0 nM and RSDs in the 5.87-16.3%
      range. The recoveries were varied from 83.6% to 113.1%. Finally, the proposed
      method was successfully applied to analyze cell secretions, and then the
      concentration of PDGF-BB and VEGF165 were detected from 5.15 nM to 2.03 nM, and
      3.14 to 2.53 nM, respectively, indicating the established method can be used to
      analyze cell secretions.

PMID- 25063922
TI  - Simple quantitation of formoterol and 11-nor-Delta(9)-tetrahydrocannabinol-9
      carboxylic acid in human urine by liquid chromatography-tandem mass spectrometry
      in doping control.
AB  - 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and formoterol
      are newly revised prohibited threshold substances (150 ng/mL for THC-COOH and 40
      ng/mL for formoterol) by the World Anti-Doping Agency (WADA). In continuation of
      our direct quantitation work of the prohibited threshold substances, direct LC
      MS/MS methods combined with a simple sample preparation procedure have been
      developed and validated for the measurement of these two threshold substances in
      urine samples. After the enzymatic hydrolysis of urine samples, the resulting
      samples were diluted with acetonitrile and centrifuged. The supernatant was
      directly analyzed by LC-MS/MS using the selected reaction monitoring mode. The
      calibration curve range of the assay was ranged over 50-200% of the threshold
      value according to WADA guidelines. The limit of detection and limit of
      quantification were 6.1 and 18.4 ng/mL for THC-COOH and 2.0 and 6.2 ng/mL for
      formoterol, respectively. Intra- and inter-day precisions were between 2.08% and
      7.28% and the accuracies ranged from 95.16% to 104.49%. The present methods were
      successfully applied to the analysis of the proficiency test samples.

PMID- 25063923
TI  - Novel regenerative large-volume immobilized enzyme reactor: preparation,
      characterization and application.
AB  - A novel large-volume immobilized enzyme reactor (IMER) on small column was
      prepared with organic-inorganic hybrid silica particles and applied for fast (10
      min) and oriented digestion of protein. At first, a thin enzyme support layer was
      formed in the bottom of the small column by polymerization with alpha-methacrylic
      acid and dimethacrylate. After that, amino SiO2 particles was prepared by the sol
      gel method with tetraethoxysilane and 3-aminopropyltriethoxysilane. Subsequently,
      the amino SiO2 particles were activated by glutaraldehyde for covalent
      immobilization of trypsin. Digestive capability of large-volume IMER for proteins
      was investigated by using bovine serum albumin (BSA), cytochrome c (Cyt-c) as
      model proteins. Results showed that although the sequence coverage of the BSA
      (20%) and Cyt-c (19%) was low, the large-volume IMER could produce peptides with
      stable specific sequence at 101-105, 156-160, 205-209, 212-218, 229-232, 257-263
      and 473-451 of the amino sequence of BSA when digesting 1mg/mL BSA. Eight of
      common peptides were observed during each of the ten runs of large-volume IMER.
      Besides, the IMER could be easily regenerated by reactivating with GA and cross
      linking with trypsin after breaking the -C=N- bond by 0.01 M HCl. The sequence
      coverage of BSA from regenerated IMER increased to 25% comparing the non
      regenerated IMER (17%). 14 common peptides. accounting for 87.5% of first use of
      IMER, were produced both with IMER and regenerated IMER. When the IMER was
      applied for ginkgo albumin digestion, the sequence coverage of two main proteins
      of ginkgo, ginnacin and legumin, was 56% and 55%, respectively. (Reviewer 2)
      Above all, the fast and selective digestion property of the large-volume IMER
      indicated that the regenerative IMER could be tentatively used for the production
      of potential bioactive peptides and the study of oriented protein digestion.

PMID- 25063924
TI  - Mass spectrometric behavior of phenolic acids standards and their analysis in the
      plant samples with LC/ESI/MS system.
AB  - Liquid chromatography coupled to mass spectrometry (MS) with electrospray
      ionization (ESI) is one of analytical techniques to obtain accurate results of
      low molecular weight aromatic compounds in biological samples of different
      origin. The interpretations of mass spectra of these aromatic compounds in the
      negative spectra registered in the full scan MS mode may be uneasy due to
      presence of deprotonated molecules [M-H](-) from different co-eluting entities,
      fragment ions created after the break-up of precursor ions and also ions
      representing modified molecules clusters. Thus, the first aim of this study was
      to evaluate general parameters during analysis performed in the full scan MS or
      MS/MS mode. Secondly, to set general fragmentation rules for aromatic compounds
      and entities in a complex biological matrix. We established that different groups
      of low molecular weight phenolic acids form unique adduct ions and additionally
      registration LC/MS/MS spectra with two different collision energies may allow for
      differentiating isomeric or isobaric molecules. These findings together with some
      general fragmentation rules can facilitate identifications of aromatic acids as
      we outlined in the sample of cold-pressed rose-hip oil and lupine leaves extract.

PMID- 25063925
TI  - Development and validation of an ultrafiltration-UPLC-MS/MS method for rapid
      quantification of unbound docetaxel in human plasma.
AB  - Docetaxel lipid microsphere (DT-LM) is a novel formulation of docetaxel without
      Tween-80. A sensitive, robust and reproducible ultrafiltration (UF) followed by
      UPLC-MS/MS method was developed and validated for the quantification of unbound
      docetaxel in human plasma using paclitaxel as IS. Ultrafiltrate samples were
      chromatographed on Acquity UPLC BEH C18 column (50 mm * 2.1 mm, 1.7 MUm). The
      mobile phase was a mixture of 10mM ammonium formate in water containing 0.2%
      formic acid (A) and acetonitrile containing 0.2% formic acid (B). The volume of
      plasma utilized was only 450 MUL. The calibration curve was linear over the range
      of 0.2-200 ng/mL, with LLOQ of 0.2 ng/mL. The method was shown to be reliable and
      reproducible with intra- and inter-day precision and accuracy <+/-15%, and
      extraction recovery of 98.1-104.8%. Docetaxel was stable during stability
      studies, e.g., short term, post-preparation and freeze-thaw cycles. The validated
      method was utilized to support the pharmacological study of DT-LM in patients
      with advanced cancer.

PMID- 25063926
TI  - Enzymatic protein digestion using a dissolvable polyacrylamide gel and its
      application to mass spectrometry-based proteomics.
AB  - Enzymatic protein digestion in polyacrylamide gel has been used for sample
      pretreatment in mass spectrometry-based proteomics due to its effectiveness in
      removing contaminants that interfere with sample ionization. However, the
      difficulty of recovering the digested peptides from the solid gel matrix has been
      a drawback of this method. Here we have developed a novel in-gel digestion method
      to enhance peptide recovery using a dissolvable, bis-acrylylcystamine (BAC)
      crosslinked polyacrylamide gel. After enzymatic protein digestion in BAC gel, we
      completely dissolved the gel by reductive treatment with tris-(2-carboxyethyl)
      phosphine to release the digested peptides from the gel. Our analysis revealed
      that the reductive dissolution of the BAC gel enhances the peptide recovery,
      which has a significantly higher protein identification capability than the
      conventional method, using an insoluble polyacrylamide gel. In addition, protein
      samples trapped in dehydrated BAC gel were stable at room temperature and
      reproducible sample recovery was obtained after storage for one week. These
      results indicate that the proposed method could be an effective tool for
      conducting sample pretreatment for mass spectrometry-based protein analysis. 

PMID- 25063927
TI  - A new HILIC-MS/MS method for the simultaneous analysis of carbidopa, levodopa,
      and its metabolites in human plasma.
AB  - Monitoring of the plasmatic levels of levodopa (LEV) and carbidopa (CAR) is
      necessary to adjust the dose of these drugs according to the individual needs of
      Parkinson's disease patients. To support drug therapeutic monitoring, a method
      using HILIC mode and LC-MS/MS was developed for the simultaneous determination of
      carbidopa, levodopa, and its metabolites (3-o-methyldopa (3-OMD) and dopamine
      (DOPA)) in human plasma. A triple quadrupole mass spectrometry was operated under
      the multiple reaction-monitoring mode (MRM) using the electrospray ionization
      technique. After straightforward sample preparation via protein precipitation, an
      Atlantis HILIC (150 * 2.1 mm, 3 MUm, Waters, USA) column were used for separation
      under the isocratic condition of acetonitrile/water (79:21, v/v) containing 0.05%
      formic acid and 3 mmol/L ammonium formate and the total run time was 7 min.
      Deuterated LEV was used as internal standard for quantification. The developed
      method was validated in human plasma with a lower limit of quantitation of 75
      ng/mL for LEV, 65 ng/mL for CAR and 3-OMD, and 20 ng/mL for DOPA. The calibration
      curve was linear within the concentration range of 75-800 ng/mL for LEV, 65-800
      ng/mL for CAR and 3-OMD, and 20-400 ng/mL for DOPA (r>0.99). The assay was
      accurate and precise, with inter-assay and intra-assay accuracies within +/
      13.44% of nominal and inter-assay and intra-assay precision<=13.99%. All results
      were within the acceptance criteria of the US FDA and ANVISA guidelines for
      method validation. LEV, CAR, 3-OMD and DOPA were stable in the battery of
      stability studies, long-term, bench-top, autosampler, and freeze/thaw cycles.
      Samples from patients undergoing treatment were analyzed, and the results
      indicated that this new method is suitable for therapeutic drug monitoring in
      Parkinson's disease patients.

PMID- 25063928
TI  - Humanized PA14 (a monoclonal CCR5 antibody) for treatment of people with HIV
      infection.
AB  - BACKGROUND: PRO 140 (a humanized form of the PA14 antibody, a monoclonal CCR5
      antibody) inhibits CCR5-tropic (R5) type 1 human immunodeficiency virus (HIV).
      This may be an effective new treatment with the potential to address the
      limitations of currently available therapies for HIV-infected patients.
      OBJECTIVES: We aimed to assess the efficacy, safety, clinical disease progression
      and immunologic (CD4 count/percentage) and virologic (plasma HIV RNA viral load)
      markers of PRO 140 for HIV-infected patients in randomized controlled trials
      (RCTs) and quasi-randomized controlled trials (quasi-RCTs). SEARCH METHODS: We
      searched databases including The Cochrane Central Register of Controlled Trials
      (The Cochrane Library 2014, Issue 4), MEDLINE (PubMed, January 1966 to April
      2014), EMBASE (January 1978 to April 2014) and ISI Web of Knowledge (January 1966
      to April 2014), online trials registries and other sources. We also screened the
      reference lists of related literature and eligible studies, and presentations
      from major HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency
      syndrome) conferences. SELECTION CRITERIA: We included RCTs and quasi-RCTs
      comparing PRO 140 with placebo or other antiretroviral drugs, or different doses
      of PRO 140 for individuals infected with HIV. DATA COLLECTION AND ANALYSIS: Two
      reviewers (L Li and JH Tian) independently screened all retrieved citations and
      selected eligible studies. Two authors (P Zhang and WQ Jia) independently
      extracted data. Any disagreements when selecting studies and extracting data were
      adjudicated by the review mentor (KH Yang). We used Review Manager (RevMan)
      software for statistical analysis based on an intention-to-treat analysis. We
      examined heterogeneity using the Chi(2) statistic. We regarded I(2) estimates
      greater than 50% as moderate or high levels of heterogeneity. According to the
      level of heterogeneity, we used either a fixed or random-effects model.If
      significant heterogeneity existed and the reasons could not be found, we reported
      the results qualitatively. MAIN RESULTS: We included three trials comparing PRO
      140 with placebo in adult patients with HIV infection. Our review indicates that
      PRO 140 may offer significant dose-dependent HIV-1 RNA suppression with tolerable
      side effects. PRO 140 2 mg/kg, 5 mg/kg, 10 mg/kg, 162 mg weekly, 324 mg biweekly,
      and 324 mg weekly showed statistically significant differences in the changes of
      HIV-1 RNA levels. HIV-1 RNA levels were reduced by intravenous (IV) infusion of
      PRO 140 2 mg/kg or 5 mg/kg on day 10, 5 mg/kg or 10 mg/kg on day 12, 162 mg
      weekly, 324 mg biweekly, or 324 mg weekly on day 22. PRO 140 2 mg/kg, 5 mg/kg, 10
      mg/kg, 162 mg weekly, 324 mg biweekly, and 324 mg weekly demonstrated greater
      antiviral response. PRO 140 324 mg weekly, 5 mg/kg, and 10 mg/kg showed more
      patients with ? 400 copies/mL HIV-1 RNA. Only PRO 140 5 mg/kg showed greater
      change in CD4(+) cell count on day eight. Headache, lymphadenopathy, diarrhoea,
      fatigue, hypertension, nasal congestion and pruritus were reported to be the most
      frequent adverse events. AUTHORS' CONCLUSIONS: Limited evidence from three small
      trials suggests that PRO 140 might demonstrate potent, short-term, dose
      dependent, highly significant antiviral activity. However, as the evidence is
      insufficient, recommendations cannot yet be made. Larger, longer-term, double
      blind RCTs are required to provide conclusive evidence.

PMID- 25063929
TI  - Effect of seepage velocity on the attachment efficiency of TiO2 nanoparticles in
      porous media.
AB  - Previously identified relationships between the attachment efficiency (alpha) and
      seepage velocity (US) of nanoparticles (NPs) were tested under simulated
      subsurface transport conditions, where the value of US is typically much less
      than the US on which they are based. This found an increase in the alpha value of
      TiO2 NPs with respect to US, which contradicts previous reports suggesting a
      constant value or decrease. By comparing the adhesion energy of the TiO2 NPs to
      sand and the hydrodynamic energy required to detach them, the increase of alpha
      with respect to US is found to be due to the difference in the magnitude of US
      considered; with 6.1E-05 to 1.3E-03ms(-1) used in previous studies, whereas the
      current study uses a value in the range from 2.4E-06 to 4.9E-04ms(-1). Only one
      of the previous models predicting alpha showed a similar increase of alpha with
      US, which was the result of it employing low velocities to examine the effects of
      organic matter. The current findings therefore suggest that previously determined
      relationships between alpha and US need to be further developed to incorporate
      more variables before they can be effectively used to describe or predict the
      subsurface transport of TiO2 NPs. 

PMID- 25063930
TI  - Removal of waterborne microorganisms by filtration using clay-polymer complexes.
AB  - Clay-polymer composites were designed for use in filtration processes for
      disinfection during the course of water purification. The composites were formed
      by sorption of polymers based on starch modified with quaternary ammonium ethers
      onto the negatively charged clay mineral bentonite. The performance of the clay
      polymer complexes in removal of bacteria was strongly dependent on the
      conformation adopted by the polycation on the clay surface, the charge density of
      the polycation itself and the ratio between the concentrations of clay and
      polymer used during the sorption process. The antimicrobial effect exerted by the
      clay-polymer system was due to the cationic monomers adsorbed on the clay
      surface, which resulted in a positive surface potential of the complexes and
      charge reversal. Clay-polymer complexes were more toxic to bacteria than the
      polymers alone. Filtration employing our optimal clay-polymer composite yielded
      100% removal of bacteria after the passage of 3L, whereas an equivalent filter
      with granular activated carbon (GAC) hardly yielded removal of bacteria after
      0.5L. Regeneration of clay-polymer complexes saturated with bacteria was
      demonstrated. Modeling of the filtration processes permitted to optimize the
      design of filters and estimation of experimental conditions for purifying large
      water volumes in short periods. 

PMID- 25063931
TI  - Nanomanipulation-coupled to nanospray mass spectrometry applied to document and
      ink analysis.
AB  - A method for the extraction and analysis of ink samples was developed using
      microscopy with direct analyte probe nanoextraction coupled to nanospray
      ionization mass spectrometry (DAPNe-NSI-MS) for localized chemical analysis of
      document inks. Nanomanipulation can be effectively coupled to nanospray
      ionization mass spectrometry providing picomolar sensitivity, and the capability
      to analyze ultra-trace amounts of material and reduce the required sample volume
      to as low as 300 nL. This new and innovative technique does not leave destructive
      footprints on the surface of a document. To demonstrate the breadth of this
      technique, analysis of inks from various eras were tested, iron gall ink and
      modern inks, as well as the capability to detect the oxidative products of
      polyethylene glycol (PEG), a common binding agent. The experimental results
      showed that DAPNe-NSI-MS was able to chelate iron(II) and manganese(II) ions of
      iron gall ink and organic components of modern and carbon-based inks. Regardless
      of whether the ink composition is modern or ancient, organic or inorganic, this
      new instrumental approach is able to identify and characterize the ingredients by
      modifying the extraction solvent, illustrating the potential diversity of the
      DAPNe technique.

PMID- 25063932
TI  - Quantitative comparison of striated toolmarks.
AB  - A comparison of striated toolmarks by human examiners is dependent on the
      experience of the expert and includes a subjective judgment within the process.
      In this article an automated method is presented for objective comparison of
      striated marks of screwdrivers. The combination of multi-scale registration
      (alignment) of toolmarks, that accounts for shift and scaling, with global cross
      correlation as objective toolmark similarity metric renders the approach robust
      with respect to large differences in angle of attack and moderate toolmark
      compression. In addition, a strategy to distinguish between relevant and non
      relevant spatial frequency ranges (geometric details) is presented. The
      performance of the method is evaluated using 3D topography scans of experimental
      toolmarks of 50 unused screwdrivers. Known match and known non-match similarity
      distributions are estimated including a large range of angles of attack (15, 30,
      45, 60 and 75 degrees ) for the known matches. It is demonstrated that the system
      has high discriminatory power, even if the toolmarks are made at a difference in
      angle of attack of larger than 15 degrees . The probability distributions are
      subsequently employed to determine likelihood ratios. A comparison of the results
      of the automated method with the outcome of a toolmark comparison experiment
      involving three experienced toolmark examiners reveals, that the automated system
      is more powerful in correctly supporting the hypothesis of common origin for
      toolmarks with a large difference in angle of attack (30 degrees ). In return,
      the rate of toolmark comparisons that yield incorrect support for the hypothesis
      of common origin is higher for the automated system. In addition, a comparison
      between estimating known match and known non-match distributions using 2D and 3D
      data is presented and it is shown that for toolmarks of unused screwdrivers,
      relying on 3D is slightly better than relying on 2D data. Finally, a comparison
      between estimating known match and known non-match distributions for two
      different types of screwdrivers suggests, that the method may be used for
      comparing marks of other tools as well. 

PMID- 25063933
TI  - Epidemiology of rapes in Costa Rica: characterization of victims, perpetrators
      and circumstances surrounding forced intercourse.
AB  - Since the year 2000, the number of rapes in Costa Rica has increased at a rate of
      42 cases per year. In 2011, 1786 rape cases were reported to the prosecution
      offices throughout the country, but only 1081 reports continued through the
      investigation process by the Judicial Investigation Agency. A randomly collected
      sample of 272 reports received by Judicial Investigation Agency, between July
      2012 and June 2013, were prospectively studied. The analysis was limited to cases
      reported within 30 days following the rape. Results indicate that most of the
      provinces in the country show an incidence of about 38 cases/100,000 inhabitants.
      Ninety-six percent of the victims were women, 50% of which were between 10 and 19
      years old. More than 99.5% of violators were men. The rape was perpetrated by a
      single aggressor in 85% of the cases. It was found that 48% of the victims were
      within the first 11 days of their menstrual cycle at the time of the attack.
      Twenty-nine percent of rapes occurred in "high rape-risk" circumstances--e.g.,
      victims attacked by strangers in public outdoors or indoors. Twenty-five percent
      of rapes occur in "moderate rape-risk" circumstances--e.g., victims attacked
      indoors at public locations or at the home other than the victim's by relatives,
      sentimental partners or acquaintances. Fifteen percent of rapes occurred in "low
      rape-risk" circumstances--e.g., victims attacked in their homes by relatives or
      sentimental partners. In 67% of the cases the perpetrator was an acquaintance of
      the victim. Eleven percent of the cases corresponded to rapes in which the
      perpetrator was a partner or ex-partner of the victim. Fourteen percent and 25%
      of rapes could be classified as "proactive drug-facilitated rapes" or
      "opportunistic drug-facilitated rapes", respectively. Semen in the vaginal fluid
      of victims and the genetic profile of the alleged perpetrator were detected in
      55% and 33% of the cases, respectively.

PMID- 25063935
TI  - Computer vision and driver distraction: developing a behaviour-flagging protocol
      for naturalistic driving data.
AB  - Naturalistic driving studies (NDS) allow researchers to discreetly observe
      everyday, real-world driving to better understand the risk factors that
      contribute to hazardous situations. In particular, NDS designs provide high
      ecological validity in the study of driver distraction. With increasing dataset
      sizes, current best practice of manually reviewing videos to classify the
      occurrence of driving behaviours, including those that are indicative of
      distraction, is becoming increasingly impractical. Current statistical solutions
      underutilise available data and create further epistemic problems. Similarly,
      technical solutions such as eye-tracking often require dedicated hardware that is
      not readily accessible or feasible to use. A computer vision solution based on
      open-source software was developed and tested to improve the accuracy and speed
      of processing NDS video data for the purpose of quantifying the occurrence of
      driver distraction. Using classifier cascades, manually-reviewed video data from
      a previously published NDS was reanalysed and used as a benchmark of current best
      practice for performance comparison. Two software coding systems were developed -
      one based on hierarchical clustering (HC), and one based on gender differences
      (MF). Compared to manual video coding, HC achieved 86 percent concordance, 55
      percent reduction in processing time, and classified an additional 69 percent of
      target behaviour not previously identified through manual review. MF achieved 67
      percent concordance, a 75 percent reduction in processing time, and classified an
      additional 35 percent of target behaviour not identified through manual review.
      The findings highlight the improvements in processing speed and correctly
      classifying target behaviours achievable through the use of custom developed
      computer vision solutions. Suggestions for improved system performance and wider
      implementation are discussed. 

PMID- 25063934
TI  - Fruit softening and pectin disassembly: an overview of nanostructural pectin
      modifications assessed by atomic force microscopy.
AB  - BACKGROUND: One of the main factors that reduce fruit quality and lead to
      economically important losses is oversoftening. Textural changes during fruit
      ripening are mainly due to the dissolution of the middle lamella, the reduction
      of cell-to-cell adhesion and the weakening of parenchyma cell walls as a result
      of the action of cell wall modifying enzymes. Pectins, major components of fruit
      cell walls, are extensively modified during ripening. These changes include
      solubilization, depolymerization and the loss of neutral side chains. Recent
      evidence in strawberry and apple, fruits with a soft or crisp texture at
      ripening, suggests that pectin disassembly is a key factor in textural changes.
      In both these fruits, softening was reduced as result of antisense downregulation
      of polygalacturonase genes. Changes in pectic polymer size, composition and
      structure have traditionally been studied by conventional techniques, most of
      them relying on bulk analysis of a population of polysaccharides, and studies
      focusing on modifications at the nanostructural level are scarce. Atomic force
      microscopy (AFM) allows the study of individual polymers at high magnification
      and with minimal sample preparation; however, AFM has rarely been employed to
      analyse pectin disassembly during fruit ripening. SCOPE: In this review, the main
      features of the pectin disassembly process during fruit ripening are first
      discussed, and then the nanostructural characterization of fruit pectins by AFM
      and its relationship with texture and postharvest fruit shelf life is reviewed.
      In general, fruit pectins are visualized under AFM as linear chains, a few of
      which show long branches, and aggregates. Number- and weight-average values
      obtained from these images are in good agreement with chromatographic analyses.
      Most AFM studies indicate reductions in the length of individual pectin chains
      and the frequency of aggregates as the fruits ripen. Pectins extracted with
      sodium carbonate, supposedly located within the primary cell wall, are the most
      affected.

PMID- 25063936
TI  - Native Hawaiian and Pacific Islander Elders: What Gerontologists Should Know.
AB  - Native Hawaiian and other Pacific Islanders (NHOPI) experience significant health
      disparities compared with other racial groups in the United States. Lower life
      expectancy has resulted in small proportions of elders in the population
      distribution of NHOPI, yet the number of NHOPI elders is growing. This article
      presents data on NHOPI elders and discusses possible reasons for continuing
      health disparities, including historical trauma, discrimination, changing
      lifestyle, and cultural values. We outline promising interventions with NHOPI and
      make suggestions for future research. 

PMID- 25063937
TI  - The Protective Effects of Religiosity on Depression: A 2-Year Prospective Study.
AB  - PURPOSE OF THE STUDY: Approximately 20% of older adults are diagnosed with
      depression in the United States. Extant research suggests that engagement in
      religious activity, or religiosity, may serve as a protective factor against
      depression. This prospective study examines whether religiosity protects against
      depression and/or aids in recovery. DESIGN AND METHODS: Study data are drawn from
      the 2006 and 2008 waves of the Health and Retirement Study. The sample consists
      of 1,992 depressed and 5,740 nondepressed older adults (mean age = 68.12 years),
      at baseline (2006), for an overall sample size of 7,732. Logistic regressions
      analyzed the relationship between organizational (service attendance),
      nonorganizational (private prayer), and intrinsic measures of religiosity and
      depression onset (in the baseline nondepressed group) and depression recovery (in
      the baseline depressed group) at follow-up (2008), controlling for other baseline
      factors. RESULTS: Religiosity was found to both protect against and help
      individuals recover from depression. Individuals not depressed at baseline
      remained nondepressed 2 years later if they frequently attended religious
      services, whereas those depressed at baseline were less likely to be depressed at
      follow-up if they more frequently engaged in private prayer. IMPLICATIONS:
      Findings suggest that both organizational and nonorganizational forms of
      religiosity affect depression outcomes in different circumstances (i.e., onset
      and recovery, respectively). Important strategies to prevent and relieve
      depression among older adults may include improving access and transportation to
      places of worship among those interested in attending services and facilitating
      discussions about religious activities and beliefs with clinicians.

PMID- 25063938
TI  - Measuring future time perspective across adulthood: development and evaluation of
      a brief multidimensional questionnaire.
AB  - PURPOSE OF THE STUDY: Despite calls for the consideration of future time
      perspective (FTP) as a multidimensional construct, mostly unidimensional
      measurement instruments have been used. This study had two objectives: (a) to
      develop a brief multidimensional questionnaire for assessing FTP in adulthood and
      evaluate its psychometric properties; and (b) to examine age associations and age
      group differences of the dimensions of FTP. DESIGN AND METHODS: Data were
      collected from 625 community-residing adults between the ages of 18 and 93,
      representing young, middle-aged, and older adults. The psychometric evaluation
      involved exploratory factor analyses (EFA) and confirmatory FA (CFA), reliability
      and validity analyses, and measurement invariance testing. Zero-order and partial
      correlations were used to examine the association of the dimensions of FTP with
      age, and multivariate analysis of variance was used to examine age-group
      differences. RESULTS: EFA and CFA supported a three-factor solution: Future as
      Open, Future as Limited, and Future as Ambiguous. Metric measurement invariance
      for this factor structure was confirmed across the three age groups. Reliability
      and validity analyses provided evidence of sound psychometric properties of the
      brief questionnaire. Age was negatively associated with Future as Open and
      positively associated with Future as Limited. Young adults exhibited
      significantly greater ambiguity toward the future than middle-aged or older
      adults. IMPLICATIONS: This study provides evidence in support of the psychometric
      properties of a new brief multidimensional FTP scale. It also provides evidence
      for a pattern of age associations and age-group differences consistent with life
      span developmental theory.

PMID- 25063939
TI  - Extending problem-solving procedures through reflection.
AB  - A large-sample (n=75) fMRI study guided the development of a theory of how people
      extend their problem-solving procedures by reflecting on them. Both children and
      adults were trained on a new mathematical procedure and then were challenged with
      novel problems that required them to change and extend their procedure to solve
      these problems. The fMRI data were analyzed using a combination of hidden Markov
      models (HMMs) and multi-voxel pattern analysis (MVPA). This HMM-MVPA analysis
      revealed the existence of 4 stages: Encoding, Planning, Solving, and Responding.
      Using this analysis as a guide, an ACT-R model was developed that improved the
      performance of the HMM-MVPA and explained the variation in the durations of the
      stages across 128 different problems. The model assumes that participants can
      reflect on declarative representations of the steps of their problem-solving
      procedures. A Metacognitive module can hold these steps, modify them, create new
      declarative steps, and rehearse them. The Metacognitive module is associated with
      activity in the rostrolateral prefrontal cortex (RLPFC). The ACT-R model predicts
      the activity in the RLPFC and other regions associated with its other cognitive
      modules (e.g., vision, retrieval). Differences between children and adults seemed
      related to differences in background knowledge and computational fluency, but not
      to the differences in their capability to modify procedures. 

PMID- 25063940
TI  - Prompt gamma ray evaluation for chlorine analysis in blended cement concrete.
AB  - Single prompt gamma ray energy has been evaluated to measure chlorine
      concentration in fly ash (FA), Super-Pozz (SPZ) and blast furnace slag (BFS)
      cement concrete specimens using a portable neutron generator-based Prompt Gamma
      Neutron Activation (PGNAA) setup. The gamma ray yield data from chloride
      concentration measurement in FA, SPZ and BFS cement concretes for 2.86-3.10, 5.72
      and 6.11MeV chlorine gamma rays were analyzed to identify a gamma ray with common
      slope (gamma ray yield/Cl conc. wt%) for the FA, BFS and SPZ cement concretes.
      The gamma ray yield data for FA and SPZ cement concretes with varying chloride
      concentration were measured previously using a portable neutron generator-based
      PGNAA setup. In the current study, new data have been measured for chlorine
      detection in the BFS cement concrete using a portable neutron generator-based
      PGNAA setup for 2.86-3.10, 5.72, and 6.11MeV chlorine gamma rays. The minimum
      detection limit of chlorine in BFS cement concrete (MDC) was found to be 0.034+/
      0.010, 0.032+/-0.010, 0.033+/-0.010 for 2.86-3.10, 5.72 and 6.11MeV gamma ray,
      respectively. The new BFS cement concrete data, along with the previous
      measurements for FA and SPZ cement concretes, have been utilized to identify a
      gamma ray with a common slope to analyze the Cl concentration in all of these
      blended cement concretes. It has been observed that the 6.11MeV chlorine gamma
      ray has a common slope of 5295+/-265 gamma rays/wt % Cl concentration for the
      portable neutron generator-based PGNAA setup. The minimum detectable
      concentration (MDC) of chlorine in blended cement concrete was measured to be
      0.033+/-0.010wt % for the portable neutron generator-based PGNAA. Thus, the
      6.11MeV chlorine gamma ray can be used for chlorine analysis of blended cement
      concretes. 

PMID- 25063941
TI  - Particulate carbon and nitrogen determinations in tracer studies: The neglected
      variables.
AB  - We address two issues in the determination of particulate carbon and nitrogen in
      suspended matter of aquatic environments. One is the adsorption of dissolved
      organic matter on filters, leading to overestimate particulate matter. The second
      is the material loss during filtration due to fragile algal cells breaking up.
      Examples from both laboratory cultures and natural samples are presented. We
      recommend using stacked filters in order to estimate the first and filtering
      different volumes of water in order to evaluate the second. 

PMID- 25063942
TI  - Radioisotope studies of the farmville meteorite using gammagamma-coincidence
      spectrometry.
AB  - Radionuclides are cosmogenically produced in meteorites before they fall to the
      surface of the Earth. Measurement of the radioactive decay of such nuclides
      provides a wealth of information on the irradiation conditions of the meteorite
      fragment, the intensity of cosmic rays in the inner solar system, and the
      magnetic activity of the Sun. We report here on the detection of (26)Al using a
      sophisticated spectrometer consisting of a HPGe detector and a NaI(Tl) annulus.
      It is shown that modern gamma-ray spectrometers represent an interesting
      alternative to other detection techniques. Data are obtained for a fragment of
      the Farmville meteorite and compared to results from Geant4 simulations. In
      particular, we report on optimizing the detection sensitivity by using suitable
      coincidence gates for deposited energy and event multiplicity. We measured an
      (26)Al activity of 48.5+/-3.5dpm/kg for the Farmville meteorite, in agreement
      with previously reported values for other H chondrites. 

PMID- 25063943
TI  - Cyclopalladated primary amines: a preliminary study of antiproliferative activity
      through apoptosis induction.
AB  - Twelve cyclometallated palladium(II) complexes containing primary aromatic amines
      [benzylamine (a), (R)-1-(1-naphthyl)ethylamine (b) and 2-phenylaniline (c)] as
      anionic bidentate (C,N)(-) ligands have been evaluated against a panel of human
      adenocarcinoma cell lines (A549 lung, MDA-MB231 and MCF7 breast, and the
      cisplatin resistant HCT116 colon). The results revealed a remarkable
      antiproliferative activity of the triphenylphosphane mononuclear compounds 3-4
      (series a, b, c) and the best inhibition was provided for 3c and 4c with the 2
      phenylaniline ligand and a six membered chelate ring. Interestingly, 3c and 4c
      were 14 and 19 times more potent than cisplatin for the inhibition of the
      cisplatin resistant HCT116 human adenocarcinoma cell line, respectively.
      Cyclopalladated complexes 3c and 4c exercise their antiproliferative activity
      over A549 cells mainly through the induction of apoptosis (38 and 31-fold
      increase in early apoptotic cells, respectively). 

PMID- 25063944
TI  - 7-Amino-2-phenylpyrazolo[4,3-d]pyrimidine derivatives: structural investigations
      at the 5-position to target human A1 and A(2A) adenosine receptors. Molecular
      modeling and pharmacological studies.
AB  - In previous research, several 7-amino-2-arylpyrazolo[4,3-d]pyrimidine derivatives
      were identified as highly potent and selective antagonists at the human A3
      adenosine receptor. Structure-activity relationship studies highlighted that
      affinity and selectivity depended on the nature of the substituents at the 5- and
      7-positions of the pyrazolo[4,3-d]pyrimidine scaffold. In particular, small
      lipophilic residues at the 5-position and a free amino group at position 7
      afforded compounds able to bind all four human (h) adenosine receptors. Hence, to
      shift affinity toward the hA1 and/or hA(2A) subtypes, alkyl and arylalkyl chains
      of different length were appended at position 5 of the 2-phenylpyrazolo[4,3
      d]pyrimidin-7-amine. Among the new compounds, a dual hA1/hA(2A) receptor
      antagonist was identified, namely the 5-(3-phenylpropyl) derivative 25, which
      shows high affinity both at human A1 (K(i) = 5.31 nM) and A(2A) (K(i) = 55 nM)
      receptors. We also obtained some potent and selective antagonists for the A1
      receptor, such as the 5-(3-arylpropyl)-substituted compounds 26-31, whose
      affinities fall in the low nanomolar range (K(i) = 0.15-18 nM). Through an in
      silico receptor-driven approach, the obtained binding data were rationalized and
      the molecular bases of the hA1 and hA(2A) AR affinity and selectivity of
      derivatives 25-31 are explained.

PMID- 25063945
TI  - Novel 18F-labeled dibenzylideneacetone derivatives as potential positron emission
      tomography probes for in vivo imaging of beta-amyloid plaques.
AB  - A series of dibenzylideneacetones were synthesized and evaluated as imaging
      probes for beta-amyloid plaques. They displayed high binding affinity to Abeta(1
      42) aggregates (K(i) = 6.4 for 8, K(i) = 3.0 for 9), and the high binding were
      confirmed by in vitro autoradiography with AD human and transgenic mouse brain
      sections. Two of them were selected for (18)F-labeling directly on the benzene
      ring. In biodistribution experiments, [(18)F]8 and [(18)F]9 displayed high
      initial uptakes (9.29 +/- 0.41 and 5.38 +/- 0.68% ID/g) and rapid washouts from
      the normal brain (brain(2 min)/brain(60 min) ratios of 21.6 and 13.4). These
      preliminary results suggest that [(18)F]8 and [(18)F]9 may be used as potential
      PET imaging agents for the detection of Abeta plaques in the brain.

PMID- 25063946
TI  - New thiophene-1,2,4-triazole-5(3)-ones: highly bioactive thiosemicarbazides,
      structures of Schiff bases and triazole-thiols.
AB  - Key compound 2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4-tiazole
      1-yl) acetohydrazide (3) was synthesized by reacting hydrazine hydrate with ethyl
      2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4-tiazole-1yl)acetate
      (2), obtained in basic media from 4-amino-5-(thiophene-2-ylmethyl)-2H-1,2,4
      triazole-3(4H)-one (1). Compound 3 was converted to thiosemicarbazide derivatives
      (4a-d) and Schiff base derivatives 6a-e and 7a-e. The treatment of compound 4
      with NaOH gave 4-amino-2-((4-(4-aryl)-5-mercapto-4H-1,2,4-triazole-3-yl)methyl)-5
      (thiophene-2-ylmethyl)-2H-1,2,4-triazole-3(4H)-ones (5a-d). All newly compounds,
      well characterized by elemental analyses, IR, (1)H NMR, (13)C NMR and mass
      spectral studies were tested for their antioxidant and antimicrobial activities.
      Thiosemicarbazide derivatives (4a-d) were highly active in two antioxidant tests
      with 69.0-88.2% DPPH. scavenging and 503-1257 MUM TEAC values, while the others
      showed lower or no activity. The results of the two antioxidant tests correlated
      well. Moreover, Thiosemicarbazide derivatives (4a-d) also showed antibacterial
      activity against Staphylococcus aureus, Bacillus cereus, and Mycobacterium
      smegmatis. Thiosemicarbazide group deserves attention in the synthesis of
      bioactive compounds.

PMID- 25063947
TI  - Structure and evaluation of antibacterial and antitubercular properties of new
      basic and heterocyclic 3-formylrifamycin SV derivatives obtained via 'click
      chemistry' approach.
AB  - Thirty four novel derivatives of 3-formylrifamycin SV were synthesized via
      reductive alkylation and copper(I)-catalysed azide-alkyne cycloaddition.
      According to the obtained results, 'click chemistry' can be successfully applied
      for modification of structurally complex antibiotics such as rifamycins, with the
      formation of desired 1,2,3-triazole products. However, when azide-alkyne
      cycloaddition on 3-formylrifamycin SV derivatives demanded higher amount of
      catalyst, lower temperature and longer reaction time because of the high
      volatility of substrates, an unexpected intramolecular condensation with the
      formation of 3,4-dihydrobenzo[g]quinazoline heterocyclic system took place.
      Structures of new derivatives in solution were determined using one- and two
      dimensional NMR methods and FT-IR spectroscopy. Computational DFT and PM6 methods
      were employed to correlate their conformation and acid-base properties to
      biological activity and establish SAR of the novel compounds. Microbiological,
      physico-chemical (logP, solubility) and structural studies of newly synthesised
      rifamycins indicated that for the presence of relatively high antibacterial (MIC
      ~0.01 nmol/mL) and antitubercular (MIC ~0.006 nmol/mL) activities, a rigid and
      basic substituent at C(3) arm, containing a protonated nitrogen atom "open"
      toward intermolecular interactions, is required.

PMID- 25063948
TI  - Circulating pathogen-associated molecular pattern - binding proteins and High
      Mobility Group Box protein 1 in nascent metabolic syndrome: implications for
      cellular Toll-like receptor activity.
AB  - OBJECTIVE: The Metabolic Syndrome, (MetS) a global epidemic, is a state of low
      grade chronic inflammation and confers an increased risk for diabetes and CVD. We
      have previously reported increased activity of the pathogen recognition
      receptors, Toll-like receptors (TLRs), TLR2 and TLR4 in MetS. We hypothesized
      that increased TLR activity in MetS is due in part to increased levels of
      circulating PAMP-binding proteins, soluble CD14 (sCD14), lipopolysaccharide
      binding protein (LBP) and the damage associated molecular pattern (DAMP), High
      Mobility Group Box protein 1 (HMGB-1). METHODS: We measured sCD14, LBP and HMGB-1
      in fasting plasma from nascent MetS (n = 37) and healthy control subjects (n =
      32) by ELISA. We also investigated the effects of sCD14 and LBP on TLR4 activity
      in human aortic endothelial cells (HAECs). RESULTS: Following adjustment for body
      mass index and waist circumference, sCD14, LBP and HMGB-1 levels remained
      significantly increased in MetS. Also their levels increased with increasing
      numbers of MetS risk factors. Only sCD14 correlated significantly with monocyte
      TLR4 protein and activity. None of these soluble biomarkers correlated with TLR2
      protein. Both sCD14 and HMGB-1 correlated significantly with HOMA-IR. In LPS
      primed HAECs, sCD14 compared to LBP, resulted in a greater increase in both TLR4
      abundance and inflammatory biomediators (NF-kappaB, IL-1beta, IL-8 and TNF
      alpha). CONCLUSION: Thus, we make the novel observation that sCD14 reflects
      increased monocyte TLR4 protein and activity in nascent MetS and by contributing
      to increased cellular inflammation could explain, in part, the increased risk for
      diabetes and CVD.

PMID- 25063950
TI  - Two-dimensional NMR spectroscopy of (13)C methanol at less than 5 MUT.
AB  - Two-dimensional (2D) spectroscopy is one of the most significant applications of
      nuclear magnetic resonance (NMR). Here, we demonstrate that the 2D NMR can be
      performed even at a low magnetic field of less than 5MUT, which is ten times less
      than the Earth's magnetic field. The pulses used in the experiment were composed
      of circularly polarized fields for coherent as well as wideband excitations.
      Since the excitation band covers the entire spectral range, the simplest two
      pulse sequence delivered the full 2D spectrum. At 5MUT, methanol with (13)C
      enriched up to 99% belongs to a strongly coupled regime, and thus its 2D spectrum
      exhibits complicated spectral correlations, which can be exploited as a
      fingerprint in chemical analysis. In addition, we show that, with compressive
      sensing, the acquisition of the 2D spectrum can be accelerated to take only 45%
      of the overall duration. 

PMID- 25063949
TI  - Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes:
      a prospective study.
AB  - OBJECTIVE: Plasma total homocysteine (tHcy) has been positively associated with
      carotid intima-media thickness (IMT) in non-diabetic populations and in a few
      cross-sectional studies of diabetic patients. We investigated cross-sectional and
      prospective associations of a single measure of tHcy with common and internal
      carotid IMT over a 6-year period in type 1 diabetes. RESEARCH DESIGN AND METHODS:
      tHcy levels were measured once, in plasma obtained in 1997-1999 from patients (n
      = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC)
      study, the observational follow-up of the Diabetes Control and Complications
      Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC
      "Year 6" (1998-2000) and "Year 12" (2004-2006), using B-mode ultra-sonography.
      RESULTS: After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1,
      7.5) MUmol/L] was significantly correlated with age, diastolic blood pressure,
      renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only,
      increasing quartiles of tHcy correlated with common and internal carotid IMT,
      again at both EDIC time-points (p < 0.01). However, multivariate logistic
      regression revealed no significant associations between increasing quartiles of
      tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest
      quintile) when adjusted for conventional risk factors. CONCLUSIONS: In a type 1
      diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in
      1997-1999 was associated with measures of common and internal carotid IMT
      measured both one and seven years later, but not with IMT progression between the
      two time-points. The data do not support routine measurement of tHcy in people
      with Type 1 diabetes.

PMID- 25063951
TI  - Spectral editing through laser-flash excitation in two-dimensional photo-CIDNP
      MAS NMR experiments.
AB  - In solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP)
      MAS NMR experiments, strong signal enhancement is observed from molecules forming
      a spin-correlated radical pair in a rigid matrix. Two-dimensional (13)C-(13)C
      dipolar-assisted rotational resonance (DARR) photo-CIDNP MAS NMR experiments have
      been applied to obtain exact chemical shift assignments from those cofactors.
      Under continuous illumination, the signals are enhanced via three-spin mixing
      (TSM) and differential decay (DD) and their intensity corresponds to the electron
      spin density in pz orbitals. In multiple-(13)C labelled samples, spin diffusion
      leads to propagation of signal enhancement to all (13)C spins. Under steady-state
      conditions, direct signal assignment is possible due to the uniform signal
      intensity. The original intensities, however, are inaccessible and the
      information of the local electron spin density is lost. Upon laser-flash
      illumination, the signal is enhanced via the classical radical pair mechanism
      (RPM). The obtained intensities are related to isotropic hyperfine interactions
      aiso and both enhanced absorptive and emissive lines can be observed due to
      differences in the sign of the local isotropic hyperfine interaction. Exploiting
      the mechanism of the polarization, selectivity can be increased by the novel time
      resolved two-dimensional dipolar-assisted rotational resonance (DARR) MAS NMR
      experiment which simplifies the signal assignment compared to complex spectra of
      the same RCs obtained by continuous illumination. Here we present two-dimensional
      time-resolved photo-CIDNP MAS NMR experiments providing both directly: signal
      assignment and spectral editing by sign and strength of aiso. Hence, this
      experiment provides a direct key to the electronic structure of the correlated
      radical pair. 

PMID- 25063952
TI  - Fourier-transform electron spin resonance with bandwidth-compensated chirp
      pulses.
AB  - Electron spin echo experiments using chirp pulses at X-band around 9GHz have been
      performed with a home-built spectrometer based on an arbitrary waveform
      generator. Primary echoes without phase dispersion were obtained by employing the
      Bohlen-Bodenhausen scheme with the refocusing pulse being half as long as the
      coherence-generating pulse. To account for physical bandwidth limitation by the
      resonator, the instantaneous sweep rate of the chirps was adapted to the
      spectrometer's frequency response function, which can be recorded from the sample
      under study within a few minutes. Such bandwidth-compensated chirp pulses are
      experimentally shown to achieve an almost uniform excitation bandwidth that
      exceeds the resonator bandwidth. This uniform excitation allows for computing
      frequency-domain spectra by Fourier-transformation (FT) of the echo signal. For a
      nitroxide in dilute solid solution with a spectral width of 200MHz, the FT EPR
      spectrum agrees remarkably well with a field-swept echo-detected EPR spectrum.
      The overall spectral perturbation for operation far beyond the resonator
      bandwidth was characterized by acquiring a 700MHz wide spectral range of a copper
      (II) EPR spectrum with nearly uniform amplitude with excitation and refocusing
      pulses of 200 and 100ns, respectively. Furthermore, peculiarities were observed
      in solid-state FT EPR spectra of disordered systems. To understand these
      peculiarities two-dimensional data sets were acquired that correlate the FT EPR
      spectrum to inversion recovery or nuclear modulation. The echo envelope
      modulation experiments reveal echo decay rates increased by enhanced
      instantaneous diffusion and passage-specific effects in the nuclear modulations.
      The latter effect can be suppressed by nuclear modulation averaging. Apparent
      longitudinal relaxation times for a given subset of orientations are influenced
      by nuclear modulation effects. Proper extraction of orientation-dependent
      relaxation times thus requires an experimental setup that minimizes the
      modulations. 

PMID- 25063953
TI  - Long-lived localization in magnetic resonance imaging.
AB  - The longitudinal nuclear relaxation time, T1, sets a stringent limit on the range
      of information that can be obtained from magnetic resonance imaging (MRI)
      experiments. Long-lived nuclear spin states provide a possibility to extend the
      timescale over which information can be encoded in magnetic resonance. We
      introduce a strategy to localize an ensemble of molecules for a significantly
      extended duration (~30 times longer than T1 in this example), using a spatially
      selective conversion between magnetization and long-lived singlet order. An
      application to tagging and transport is proposed. 

PMID- 25063954
TI  - Accurate scoring of non-uniform sampling schemes for quantitative NMR.
AB  - Non-uniform sampling (NUS) in NMR spectroscopy is a recognized and powerful tool
      to minimize acquisition time. Recent advances in reconstruction methodologies are
      paving the way for the use of NUS in quantitative applications, where accurate
      measurement of peak intensities is crucial. The presence or absence of NUS
      artifacts in reconstructed spectra ultimately determines the success of NUS in
      quantitative NMR. The quality of reconstructed spectra from NUS acquired data is
      dependent upon the quality of the sampling scheme. Here we demonstrate that the
      best performing sampling schemes make up a very small percentage of the total
      randomly generated schemes. A scoring method is found to accurately predict the
      quantitative similarity between reconstructed NUS spectra and those of fully
      sampled spectra. We present an easy-to-use protocol to batch generate and rank
      optimal Poisson-gap NUS schedules for use with 2D NMR with minimized noise and
      accurate signal reproduction, without the need for the creation of synthetic
      spectra. 

PMID- 25063955
TI  - Polar polycyclic aromatic compounds from different coal types show varying
      mutagenic potential, EROD induction and bioavailability depending on coal rank.
AB  - Investigations of the bioavailability and toxicity of polycyclic aromatic
      compounds (PAC) have rarely considered the heterogeneity of coals and the impact
      of more polar PAC besides polycyclic aromatic hydrocarbons (PAH). Earlier, we
      investigated the toxicity of eight heterogeneous coals and their extracts. In the
      present study, the hazard potential with respect to mechanism-specific toxicity
      of polar fractions of dichloromethane extracts from coals was studied. Polar
      extract fractions of all coal types except for anthracite induced EROD activity
      (determined in RTL-W1 cells), independent of coal type (Bio-TEQs between 23 +/-
      16 and 52 +/- 22 ng/g). The polar fractions of all bituminous coal extracts
      revealed mutagenic activity (determined using the Ames Fluctuation test). No
      significant mutation induction was detected for the polar extract fractions from
      the lignite, sub-bituminous coal and anthracite samples, which indicates a higher
      dependency on coal type for polar PAC here. Additionally, information on
      bioavailability was derived from a bioaccumulation test using the deposit-feeding
      oligochaete Lumbriculus variegatus which was exposed for 28 days to ground coal
      samples. Despite the high toxic potential of most coal extracts and a reduced
      biomass of Lumbriculus in bituminous coal samples, bioaccumulation of PAH and
      mortality after 28 days were found to be low. Limited bioaccumulation of PAH (up
      to 3.6 +/- 3.8 mg/kg EPA-PAH) and polar PAC were observed for all coal samples. A
      significant reduction of Lumbriculus biomass was observed in the treatments
      containing bituminous coals (from 0.019 +/- 0.004 g to 0.046 +/- 0.011 g compared
      to 0.080 +/- 0.025 g per replicate in control treatments). We conclude that
      bioavailability of native PAC from coals including polar PAC is low for all
      investigated coal types. In comparison to lignite, sub-bituminous coals and
      anthracite, the bioavailability of PAC from bituminous coals is slightly
      increased.

PMID- 25063956
TI  - Family investment responses to childhood health conditions: intrafamily
      allocation of resources.
AB  - The onset of a health condition during childhood impairs skill formation. A
      number of studies have investigated the long-lasting effects of poor health
      during childhood on later-in-life outcomes. However, this evidence ignores how
      parents respond to the onset of health conditions. Do their investments reinforce
      the health condition? Or compensate, or behave neutrally? If parents change their
      investments, the relationship between early health and later outcomes combines
      the biological effect and the investment responses. To address this question, I
      use within-sibling variation in the incidence of health conditions to control for
      selection from unobserved household heterogeneity. Parents invest, on average,
      0.16 standard deviations less in children with mental conditions relative to
      their healthy siblings, using a measure of investment that includes time and
      resources. On the contrary, when children have a physical condition, parental
      investments do not differ across siblings. Results are robust to alternative
      measures of health conditions and the inclusion of child fixed effects. 

PMID- 25063957
TI  - Affective temperament and executive functions in emergency medicine
      professionals.
AB  - BACKGROUND: Recent studies indicate that choice of profession is related to
      differences in affective temperament, which is probably due to various
      predispositions needed to efficiently perform particular professions. The aim of
      the present study was to assess affective temperament and executive functions in
      a sample of emergency medicine professionals. METHODS: 75 emergency medicine
      professionals were enrolled in the study. Affective temperament was assessed by
      means of TEMPS-A. Executive functions were assessed by means of Trail Making Test
      and Stroop Color Word Interference Test. RESULTS: Subjects showed significantly
      higher rates of hyperthymic, compared to depressive, cyclothymic, irritable and
      anxious temperaments. The principal component analysis revealed that hyperthymic
      temperament contributes to a different factor, than the remaining ones. Higher
      rates of depressive, cyclothymic, irritable and anxious temperaments were related
      to poorer performance in Trail Making Test, whereas hyperthymic temperament had
      the opposite effect. LIMITATIONS: Due to the size of the sample, results of the
      present study may have lacked power to show all the relationships between tested
      variables. CONCLUSIONS: Hyperthymic temperament promotes efficient performance of
      complex tasks under time pressure. Depressive, cyclothymic, irritable and anxious
      temperaments have the opposite effect. This makes hyperthymic temperament a
      desirable trait in emergency medicine professionals, performing complex medical
      tasks under extreme conditions.

PMID- 25063958
TI  - Commingling analysis of age-of-onset in bipolar I disorder and the morbid risk
      for major psychoses in first degree relatives of bipolar I probands.
AB  - BACKGROUND: Age-of-onset (AO) is increasingly used in molecular genetics of
      bipolar I disorder (BP-I) as a phenotypic specifier with the goal of reducing
      genetic heterogeneity. However, questions regarding the cut-off age for defining
      early onset (EO), as well as the number of onset groups characterizing BP-I have
      emerged over the last decade with no definite conclusion. The aims of this paper
      are: 1) to see whether a mixture of three distributions better describes the AO
      of BP-I than a mixture of two distributions in different independent samples; 2)
      to compare the morbid risk (MR) for BP-I and for major affective disorders and
      schizophrenia in first degree relatives of BP-I probands by proband onset group
      derived from commingling analysis, since the MR to relatives is a trait with
      strong genetic background. METHODS: We applied commingling (admixture) analysis
      to the AO of three BP-I samples from Romania (n=621), Germany (n=882), and Poland
      (n=354). Subsequently, the morbid risk (MR) for BP-I and for major psychoses (BP
      I, BP-II, Mdd-UP, schizoaffective disorders, schizophrenia) was estimated in
      first degree relatives by proband AO-group derived from admixture analysis in the
      Romanian sample. RESULTS: In the three independent samples and in the combined
      sample two- and three-AO-group distributions fitted the empirical data equally
      well. The upper EO limit varied between 21 and 25 years from sample to sample.
      The MR for both BP-I and for all major psychoses was similar in first degree
      relatives of EO probands (AO<=21) and in relatives of intermediate-onset probands
      (AO=22-34). Significant MR differences appeared only when comparing the EO group
      to the late-onset (LO) group (AO>34). Similar to Mdd-UP and schizophrenia, a
      significant MR decrease in proband first degree relatives was visible after
      proband AO of 34 years. Under the three-AO-group classification the MR for both
      BP-I and all major psychoses in first degree relatives did not differ by relative
      sex in any proband AO-group. Under the two-AO-group classification female
      relatives of LO probands (AO>24) had a significantly higher MR for all major
      psychoses than male relatives, while there was no sex difference for the
      relatives of EO probands. LIMITATIONS: MR was not computed in the German and
      Polish samples because family data were not available and 34% of the relatives of
      the Romanian probands were not available for direct interview. CONCLUSION:
      Similar to other clinical traits, the MR for major psychoses to relatives failed
      to support a three-AO-group classification in BP-I suggesting that this is not
      more useful for the molecular analysis than a two-AO-group classification.

PMID- 25063959
TI  - Mindfulness-based cognitive therapy for seasonal affective disorder: a pilot
      study.
AB  - BACKGROUND: The best available treatment for seasonal affective disorder (SAD) is
      light therapy. Yet, this treatment does not prevent recurrence of depression in
      subsequent seasons. The aim of the study is to gain preliminary insight in the
      efficacy of Mindfulness Based Cognitive Therapy (MBCT) in the prevention of SAD
      recurrence. METHODS: This is a randomized controlled pilot study, in which SAD
      patients in remission were randomly allocated to an individual format of MBCT or
      a control condition (i.e. treatment as usual). MBCT was given between May and
      June 2011, when there was no presence of depressive symptoms. The Inventory for
      Depressive Symptomatology Self-Report (IDS-SR), which patients received on a
      weekly basis from September 2011 to April 2012, was used to assess moment of
      recurrence (>=20) and severity at moment of recurrence. RESULTS: 23 SAD patients
      were randomized to MBCT and 23 to the control condition. Kaplan-Meier survival
      curve showed that the groups did not differ in moment of recurrence (chi2(1).41,
      p=.52). T-tests showed no group difference in mean IDS-SR scores at moment of
      recurrence (t(31)=-.52, p=.61). LIMITATIONS: The results are limited by small
      sample size (n=46) and missing data of weekly IDS-SR assessments. CONCLUSION: The
      findings of this pilot RCT suggest that individual MBCT is not effective in
      preventing a SAD recurrence when offered in a symptom free period (i.e. spring).

PMID- 25063960
TI  - Seasonality and bipolar disorder: a systematic review, from admission rates to
      seasonality of symptoms.
AB  - INTRODUCTION: Bipolar disorder (BD) is a severe mental disorder affecting 1-4% of
      the population worldwide. It is characterized by periods of (hypo)manic and
      depressive episodes. Seasonal patterns (SP) may be observed in admission rates,
      mood relapses and symptom fluctuations. METHODS: We conducted a systematic review
      of seasonality in BD, classifying studies based on seasonal admission rates to
      seasonality of symptoms assessments. RESULTS: Fifty-one papers were identified of
      which 32 addressed hospitalization rates by season, 6 addressed categorical
      diagnoses, and 13 explored symptom dimensions. Seasonal peaks for different BD
      mood episodes are observed worldwide and widely replicated. Manic episodes peak
      during spring/summer and, to a lesser extent, in autumn, depressive episodes peak
      in early winter and, to a lesser extent, summer, and mixed episodes peak in early
      spring or mid/late summer. There was a high frequency of SP for manic episodes
      (15%) and depressive episodes (25%), the latter being associated with a more
      complex clinical profile (BD II subtype, comorbid eating disorders, more relapses
      and rapid cycling). Finally, there was evidence for greater seasonal fluctuations
      in mood and behavior in individuals with BD than in those with unipolar
      depression or 'healthy' controls. LIMITATIONS: Sample size, gender distribution,
      methodological quality and sophistication of the analytical approaches employed
      varied considerably. CONCLUSIONS: There is evidence of seasonality in BD, with
      emerging evidence that climatic conditions may trigger BD symptoms or episodes. A
      better understanding of the underlying mechanisms would facilitate the
      development of personalized chronobiological therapeutic and preventive
      strategies.

PMID- 25063961
TI  - Mechanistic and kinetic studies on OH-initiated atmospheric oxidation degradation
      of benzo[alpha]pyrene in the presence of O2 and NO(x).
AB  - The degradation of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere can
      lead to toxic derivatives which contribute to the carcinogenic potential of
      particulate organic matter. This paper aimed to investigate the mechanism of the
      OH-initiated oxidation degradation of benzo[alpha]pyrene (BaP), a cancer risk
      indicator. High-accuracy molecular orbital calculations were carried out, and all
      of the possible degradation pathways were discussed. The theoretical results were
      compared with the available experimental observation. The possible secondary
      reactions were also investigated. The rate constants of the crucial elementary
      steps were evaluated by using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory.
      The dominant degradation products involve benzo[alpha]pyren-ol, nitro
      benzo[alpha]pyrene, benzo[alpha]pyrene-7,10-dione as well as several ring-opened
      products such as alkyl substituted benzanthraldehyde et al. In particular, water
      plays an important role in the degradation pathways leading to the formation of
      nitro-benzo[alpha]pyrene. This work provides a comprehensive investigation of the
      OH-initiated degradation of BaP and should help to clarify its potential risk. 

PMID- 25063962
TI  - Invertebrate grazers affect metal/metalloid fixation during litter decomposition.
AB  - Plant litter and organic sediments are main sinks for metals and metalloids in
      aquatic ecosystems. The effect of invertebrates as key species in aquatic litter
      decomposition on metal/metalloid fixation by organic matter is described only for
      shredders, but for grazers as another important animal group less is known.
      Consequently, a laboratory batch experiment was conducted to examine the effect
      of invertebrate grazers (Lymnaea stagnalis L.) on metal/metalloid
      fixation/remobilization during aquatic litter decomposition. It could be shown
      that invertebrate grazers facilitate significantly the formation of smaller sizes
      of particulate organic matter (POM), as shown previously for invertebrate
      shredders. The metal/metalloid binding capacity of these smaller particles of POM
      is higher compared to leaf litter residuals. But element enrichment is not as
      high as shown previously for the effect by invertebrate shredders. Invertebrate
      grazers enhance also the mobilization of selected elements to the water, in the
      range also proven for invertebrate shredders but different for the different
      elements. Nonetheless invertebrate grazers activity during aquatic litter
      decomposition leads to a metal/metalloid fixation into leaf litter as part of
      sediment organic matter. Hence, the effect of invertebrate grazers on
      metal/metalloid fixation/remobilization contrasts partly with former assessments
      revealing the possibility of an enhanced metal/metalloid fixation. 

PMID- 25063963
TI  - The size distribution of chemical elements of atmospheric aerosol at a semi-rural
      coastal site in Venice (Italy). The role of atmospheric circulation.
AB  - The concentrations of selected elemental tracers were determined in the aerosol
      of a semi-rural coastal site near Venice (Italy). Size-segregated aerosol samples
      were collected using an 8-stage cascade impactor set at 15m above ground, during
      the cold season (late autumn and winter), when high levels of many pollutants are
      known to cause risks for human health. From the experimental data, information
      was extracted on potential pollutant sources by investigating the relationships
      between elements in the different size fractions. Moreover, an approach to
      highlight the importance of local atmospheric circulation and air mass origin in
      influencing the PM composition and fractional distribution is proposed.
      Anthropogenic elements are strongly inter-correlated in the submicrometric (<1
      MUm) (S, K, Mn, Cu, Fe and Zn) and intermediate mode (1-4 MUm) (Mn, Cu, Zn, Ni)
      and their relationships highlight the presence of several sources (combustions,
      secondary aerosol, road traffic). In the intermediate mode, associations having
      geochemical significance exist between marine (Na, Cl and Mg) and crustal (Si,
      Mg, Ca, Al, Ti and K) elements. In the coarse mode (>4 MUm) Fe and Zn are well
      correlated and are probably linked to tire and brake wear emissions. Regarding
      atmospheric circulation, results show increasing levels of elements related to
      pollution sources (S, K, Mn, Ni, Cu, Zn) when air masses come from Central and
      Eastern Europe direction and on the ground wind blows from NWN-N-NE (from
      mainland Venice). Low wind speed and high percentage of wind calm hours favor
      element accumulation in the submicrometric and intermediate modes. Furthermore,
      strong winds favor the formation of sea-spray and the increase of Si in the
      coarse mode due to the resuspension of sand fine particles.

PMID- 25063964
TI  - Ecological risk assessment of the antibiotic enrofloxacin applied to Pangasius
      catfish farms in the Mekong Delta, Vietnam.
AB  - Antibiotics applied in aquaculture production may be released into the
      environment and contribute to the deterioration of surrounding aquatic
      ecosystems. In the present study, we assessed the ecological risks posed by the
      use of the antibiotic enrofloxacin (ENR), and its main metabolite ciprofloxacin
      (CIP), in a Pangasius catfish farm in the Mekong Delta region, Vietnam. Water and
      sediment samples were collected in a stream receiving effluents from a Pangasius
      catfish farm that had applied ENR. The toxicity of ENR and CIP was assessed on
      three tropical aquatic species: the green-algae Chlorella sp. (72 h - growth
      inhibition test), the micro-invertebrate Moina macrocopa (48 h - immobilization
      test), and the Nile tilapia (Oreochromis niloticus). The toxic effects on O.
      niloticus were evaluated by measuring the cholinesterase (ChE) and catalase (CAT)
      activities in the fish brain and muscles, respectively, and by considering feed
      exposure and water exposure separately. Ecological risks were assessed by
      comparing maximum exposure concentrations with predicted no effect concentrations
      for cyanobacteria, green algae, invertebrates and fish derived with available
      toxicity data. The results of this study showed that maximum antibiotic
      concentrations in Pangasius catfish farm effluents were 0.68 MUg L(-1) for ENR
      and 0.25 MUg L(-1) for CIP (dissolved water concentrations). Antibiotics
      accumulated in sediments down-stream the effluent discharge point at
      concentrations up to 2590 MUg kg(-1) d.w. and 592 MUg kg(-1) d.w. for ENR and
      CIP, respectively. The calculated EC50 values for ENR and CIP were 111000 and
      23000 MUg L(-1) for Chlorella sp., and 69000 and 71000 MUg L(-1) for M.
      macrocopa, respectively. Significant effects on the ChE and CAT enzymatic
      activities of O. niloticus were observed at 5 g kg(-1) feed and 400-50000 MUg L(
      1), for both antibiotics. The results of the ecological risk assessment performed
      in this study indicated only minor risks for cyanobacteria communities,
      suggesting that residual concentrations of ENR and CIP after medication are not
      likely to result in severe toxic effects on exposed aquatic ecosystems. However,
      more studies should be performed by considering other antibiotic treatments used
      in Pangasius catfish production and the potential ecotoxicological effects of
      relevant antibiotic mixtures on sediment communities.

PMID- 25063965
TI  - 'It is hard for mums to put themselves first': how mothers diagnosed with breast
      cancer manage the sociological boundaries between paid work, family and caring
      for the self.
AB  - This paper aims to increase understanding of how mothers diagnosed with breast
      cancer while in the paid workforce experience and manage their multiple demands
      of taking care of themselves, their children and their paid work. In-depth, semi
      structured interviews were conducted with 32 women who were mothers of dependent
      children and in the paid workforce at the time of their breast cancer diagnosis.
      The sample includes women living in urban and rural Australia. The study found
      that after a breast cancer diagnosis, participants tended to prioritise their
      health and wellbeing over paid work. Yet dominance of gendered identity meant
      that they tended to place the needs of family, especially children, above their
      own health and wellbeing. The key factors that influenced mothers' decisions to
      continue in, return to, or leave paid work after a breast cancer diagnosis
      included: a change in perspective regarding what was important in their lives;
      level of support from the workplace and home; the extent to which participating
      in paid work was a financial necessity; the extent to which their identity was
      connected to paid work, and; ongoing level of pain or fatigue. The paper
      concludes that using the sociological concepts of the fateful moment, boundary
      maintenance and a feminist ethic of care produces a more nuanced understanding of
      women's participation in paid work after breast cancer than examining paid
      workforce participation, or unpaid responsibilities and mothering, separately.
      The nature of the permeability or malleability of boundaries between work, family
      and taking care of the self affects women's participation in paid work during
      and/or after breast cancer treatment. Increased boundary permeability or
      malleability brought about more by cooperation than conflict facilitated positive
      experiences of re-negotiating boundaries, whereas increased permeability or
      malleability brought about more by conflict than cooperation created difficulties
      for women in finding an acceptable balance between their family, paid work and
      taking care of their own health after breast cancer. 

PMID- 25063966
TI  - Negotiating jurisdiction in the workplace: a multiple-case study of nurse
      prescribing in hospital settings.
AB  - This paper reports on a multiple-case study of prescribing by nurse specialists
      in Dutch hospital settings. Most analyses of interprofessional negotiations over
      professional boundaries take a macro sociological approach and ignore workplace
      jurisdictions. Yet boundary blurring takes place and healthcare professionals
      renegotiate formal policies in the workplace. This paper studies the division of
      jurisdictional control over prescribing between nurse specialists and medical
      specialists in the workplace, and examines the relationship between workplace
      jurisdiction and legal jurisdiction over prescribing. Data collection took place
      in the Netherlands during the first half of 2013. The study used in-depth
      interviews with fifteen nurse specialists and fourteen medical specialists, non
      participant observation of nurse specialists' prescribing consultations and
      document analysis. Great variety was found in the extent to which and way in
      which nurse specialists' legal prescriptive authority had been implemented. These
      findings suggest that there is considerable discrepancy between the division of
      jurisdictional control over prescribing at the macro (legal) level and the
      division at the micro (workplace) level. 

PMID- 25063967
TI  - Social recovery and the move beyond deficit models of depression: a feminist
      analysis of mid-life women's self-care practices.
AB  - In Australia, like other advanced liberal democracies, the adoption of a recovery
      orientation was hailed as a major leap forward in mental health policy and
      service provision. We argue that this shift in thinking about the meaning of
      recovery requires further analysis of the gendered dimension of self-identity and
      relationships with the social world. In this article we focus on how mid-life
      women constructed meaning about recovery through their everyday practices of self
      care within the gendered context of depression. Findings from our qualitative
      research with 31 mid-life women identified how the recovery process was
      complicated by relapses into depression, with many women critically questioning
      the limitations of biomedical treatment options for a more relational
      understanding of recovery. Participant stories revealed important tacit knowledge
      about recovery that emphasised the process of realising and recognising
      capacities and self-knowledge. We identify two central themes through which
      women's tacit knowledge of this changing relation to self in recovery is made
      explicit: the disciplined self of normalised recovery, redefining recovery and
      depression. The findings point to the need to reconsider how both recovery
      discourses and gendered expectations can complicate women's experiences of moving
      through depression. We argue for a different conceptualisation of recovery as a
      social practice through which women realise opportunities to embody different
      'beings and doings'. A gendered understanding of what women themselves identify
      is important to their well-being, can contribute to more effective recovery
      oriented policies based on capability rather than deficit. 

PMID- 25063968
TI  - Understanding the adoption dynamics of medical innovations: affordances of the da
      Vinci robot in the Netherlands.
AB  - This study explored the rather rapid adoption of a new surgical device - the da
      Vinci robot - in the Netherlands despite the high costs and its controversial
      clinical benefits. We used the concept 'affordances' as a conceptual-analytic
      tool to refer to the perceived promises, symbolic meanings, and utility values of
      an innovation constructed in the wider social context of use. This concept helps
      us empirically understand robot adoption. Data from 28 in-depth interviews with
      diverse purposively-sampled stakeholders, and from medical literature, policy
      documents, Health Technology Assessment reports, congress websites and patients'
      weblogs/forums between April 2009 and February 2014 were systematically analysed
      from the perspective of affordances. We distinguished five interrelated
      affordances of the robot that accounted for shaping and fulfilling its rapid
      adoption: 'characteristics-related' affordances such as smart nomenclature and
      novelty, symbolising high-tech clinical excellence; 'research-related'
      affordances offering medical-technical scientific excellence; 'entrepreneurship
      related' affordances for performing better-than-the-competition; 'policy-related'
      affordances indicating the robot's liberalised provision and its reduced
      financial risks; and 'communication-related' affordances of the robot in shaping
      patients' choices and the public's expectations by resonating promising
      discourses while pushing uncertainties into the background. These affordances
      make the take-up and use of the da Vinci robot sound perfectly rational and
      inevitable. This Dutch case study demonstrates the fruitfulness of the
      affordances approach to empirically capturing the contextual dynamics of
      technology adoption in health care: exploring in-depth actors' interaction with
      the technology while considering the interpretative spaces created in situations
      of use. This approach can best elicit real-life value of innovations, values as
      defined through the eyes of (potential) users. 

PMID- 25063969
TI  - Health system reform in rural China: voices of healthworkers and service-users.
AB  - Like many other countries China is undergoing major health system reforms, with
      the aim of providing universal health coverage, and addressing problems of low
      efficiency and inequity. The first phase of the reforms has focused on
      strengthening primary care and improving health insurance coverage and benefits.
      The aim of the study was to explore the impacts of these reforms on healthworkers
      and service-users at township level, which has been the major target of the first
      phase of the reforms. From January to March 2013 we interviewed eight health
      officials, 80 township healthworkers and 80 service-users in eight counties in
      Zhejiang and Yunnan provinces, representing rich and poor provinces respectively.
      Thematic analysis identified key themes around the impacts of the health reforms.
      We found that some elements of the reforms may actually be undermining primary
      care. While the new health insurance system was popular among service-users, it
      was criticised for contributing to fast-growing medical costs, and for an
      imbalance of benefits between outpatient and inpatient services. Salary reform
      has guaranteed healthworkers' income, but greatly reduced their incentives. The
      essential drug list removed perverse incentives to overprescribe, but led to
      falls in income for healthworkers, and loss of autonomy for doctors. Serious
      problems with drug procurement also emerged. The unintended consequences have
      included a brain drain of experienced healthworkers from township hospitals, and
      patients have flowed to county hospitals at greater cost. In conclusion, in the
      short term resources must be found to ensure rural healthworkers feel
      appropriately remunerated and have more clinical autonomy, measures for
      containment of the medical costs must be taken, and drug procurement must show
      increased transparency and accountability. More importantly the study shows that
      all countries undergoing health reforms should elicit the views of stakeholders,
      including service-users, to avoid and address unintended consequences. 

PMID- 25063970
TI  - Non-coding RNA and the complex regulation of the trypanosome life cycle.
AB  - The protozoan parasite Trypanosoma brucei is the causative agent of African
      sleeping sickness and the wasting disease, nagana, in cattle. The parasite is
      transmitted to the mammalian host by the bite of a tsetse fly. These parasites
      lack transcriptional regulation, and their gene expression is mainly regulated
      post-transcriptionally. Changes in the transcriptome and proteome suggest that
      mRNA stability and translation regulation operate to control cycling between the
      hosts. The review discusses the small RNome of T. brucei, and the potential
      involvement of these molecules in shaping the adaptation of the parasites to
      their hosts. 

PMID- 25063971
TI  - Immunopharmacological modulation of mast cells.
AB  - Mast cells produce a wide spectrum of mediators and they have been implicated in
      several physiopathological conditions (e.g. allergic reactions and certain
      tumors). Pharmacologic agents that modulate the release of mediators from mast
      cells has helped to elucidate the biochemical mechanisms by which immunological
      and non-immunological stimuli activate these cells. Furthermore, the study of
      surface receptors and signaling pathways associated with mast cell activation
      revealed novel pharmacologic targets. Thus, the development of pharmacologic
      agents based on this new wave of knowledge holds promise for the treatment of
      several mast cell-mediated disorders. 

PMID- 25063972
TI  - Understanding the role of extracellular polymeric substances in an enhanced
      biological phosphorus removal granular sludge system.
AB  - The role of extracellular polymeric substances (EPS) in the enhanced biological
      phosphorus removal (EBPR) process was investigated in a P-accumulating granular
      sludge system by analyzing the distribution and transfer of P, K(+), Mg(2+) and
      Ca(2+) in the sludge phase, EPS, and the bulk liquid. In the sludge phase, about
      30% P, 44.7% K(+), 27.7% Mg(2+), 28% Ca(2+) accumulated in the EPS at the end of
      aeration. The rate of P, K(+), Mg(2+) and Ca(2+) released from the EPS matrix
      into the bulk liquid in the anaerobic phase was faster than the rate they were
      adsorbed from the bulk liquid into the EPS in the aerobic phase. P, K(+), Mg(2+)
      and Ca(2+) were retained in EPS before transferring into the phosphorus
      accumulating organisms (PAOs). These results suggest that EPS play a critical
      role in facilitating the accumulation and transfer of P, K(+), Ca(2+) and Mg(2+)
      between PAO cells and bulk liquid. 

PMID- 25063973
TI  - Effects of heating rate on slow pyrolysis behavior, kinetic parameters and
      products properties of moso bamboo.
AB  - Effects of heating rate on slow pyrolysis behaviors, kinetic parameters, and
      products properties of moso bamboo were investigated in this study. Pyrolysis
      experiments were performed up to 700  degrees C at heating rates of 5, 10, 20,
      and 30  degrees C/min using thermogravimetric analysis (TGA) and a lab-scale
      fixed bed pyrolysis reactor. The results show that the onset and offset
      temperatures of the main devolatilization stage of thermogravimetry/derivative
      thermogravimetry (TG/DTG) curves obviously shift toward the high-temperature
      range, and the activation energy values increase with increasing heating rate.
      The heating rate has different effects on the pyrolysis products properties,
      including biochar (element content, proximate analysis, specific surface area,
      heating value), bio-oil (water content, chemical composition), and non
      condensable gas. The solid yields from the fixed bed pyrolysis reactor are
      noticeably different from those of TGA mainly because the thermal hysteresis of
      the sample in the fixed bed pyrolysis reactor is more thorough.

PMID- 25063974
TI  - Action spectra of oxygen production and chlorophyll a fluorescence in the green
      microalga Nannochloropsis oculata.
AB  - The first complete action spectrum of oxygen evolution and chlorophyll a
      fluorescence was measured for the biofuel candidate alga Nannochloropsis oculata.
      A novel analytical procedure was used to generate a representative and
      reproducible action spectrum for microalgal cultures. The action spectrum was
      measured at 14 discrete wavelengths across the visible spectrum, at an equivalent
      photon flux density of 60 MUmol photon sm(-2) s(-1). Blue light (~ 414 nm) was
      absorbed more efficiently and directed to photosystem II more effectively than
      red light (~ 679 nm) at light intensities below the photosaturation limit.
      Conversion of absorbed photons into photosynthetic oxygen evolution was maximised
      at 625 nm; however, this maximum is unstable since neighbouring wavelengths (646
      nm) resulted in the lowest photosystem II operating efficiency. Identifying the
      wavelength-dependence of photosynthesis has clear implications to optimising
      growth efficiency and hence important economic implications to the algal biofuels
      and bioproducts industries.

PMID- 25063975
TI  - Isolation and characterization of microalgae for biodiesel production from
      Nisargruna biogas plant effluent.
AB  - Increasing energy demand and depleting fossil fuel sources have intensified the
      focus on biofuel production. Microalgae have emerged as a desirable source for
      biofuel production because of high biomass and lipid production from waste water
      source. In this study, five microalgae were isolated from effluents of Nisargruna
      biogas plants. These isolates were identified based on morphology and partial 18S
      and 23S rRNA gene sequences. Growth and lipid accumulation potential of these
      microalgae were investigated. One isolate, Chlorella sp. KMN3, accumulated high
      biomass (1.59 +/- 0.05 g L(-1)) with moderate lipid content (20%), while another
      isolate Monoraphidium sp. KMN5 showed moderate biomass accumulation of 0.65 +/-
      0.05 g L(-1) with a very high (35%) lipid content. The fatty acid methyl esters
      mainly composed of C-16:0, C-18:0, C-18:1 and C-18:2. This observation makes
      these microalgae immensely potential candidate for biodiesel production using the
      effluent of a biogas plant as feed stock.

PMID- 25063976
TI  - Recyclability of an ionic liquid for biomass pretreatment.
AB  - This study investigated the possibility of reusing an ionic liquid for the
      pretreatment of biomass. The effects of lignin and water content in a
      pretreatment solvent on pretreatment products were examined, along with the
      recyclability of an ionic liquid for pretreatment. It was discovered that the
      presence of lignin and water within a pretreatment solvent resulted in a far less
      effective pretreatment process. 1-Ethyl-3-methylimidazolium acetate/ethanolamine
      (60/40 vol%) presents more promising properties than EMIM-AC, providing a small
      decrease in sugar conversion and also a small increase of lignin deposition with
      an increasing lignin amount in the pretreatment solvent. Deteriorations of the
      ionic liquid were observed from considerably low sugar conversions and lignin
      extraction after using the 5th and 7th batch, respectively. Furthermore, the
      changes of ionic liquid properties and lignin accumulation in ionic liquid were
      determined by analyzing their thermal decomposition behavior (TGA) and chemical
      functional groups (FTIR and (1)H NMR).

PMID- 25063977
TI  - Microbial communities of aerobic granules: granulation mechanisms.
AB  - Aerobic granulation is an advanced biological wastewater treatment technology.
      This study for the first time identified the microbial communities of sliced
      samples of mature granules by polymerase chain reaction (PCR) amplification and
      denaturing gradient gel electrophoresis (DGGE) technique and those of whole
      growing granules by high-throughput sequencing technique. The sliced sample study
      revealed that mature granules have a spherical core with anaerobic Rhodocyclaceae
      covered by an outer spherical shell with both aerobic and anaerobic strains. The
      growing granule study showed that the flocculated flocs were first transited to
      young granules with increased abundances of Flavobacteriaceae, Xanthomonadaceae,
      Rhodobacteraceae and Microbacteriaceae, then the abundances of anaerobic strains
      were increased owing to the formation of anaerobic core. Since the present
      granules were cultivated from flocculated flocs, the microbial community data
      suggested that granules were formed via a deterministic rather than via a random
      aggregation-disintegration mechanism. 

PMID- 25063978
TI  - Behavior of selected hydrolyzed and dehydrated products during hydrothermal
      carbonization of biomass.
AB  - In this study, effects of reaction temperature and reaction time on both solid
      hydrochar and HTC process liquid products were studied for hydrothermal
      carbonization (HTC) of cellulose, wheat straw, and poplar. A novel slurry
      sampling system was designed and used with an 18.6L Parr reactor for 0-480 min in
      200, 230, and 260  degrees C. Sugars (sucrose, glucose, and fructose), HMF, and
      furfural were found maximum in lower HTC temperature and time. However, they
      degrade following first order degradation kinetics. Activation energies of total
      sugars (glucose, fructose, sucrose, and xylose), furfural, and HMF for straw and
      poplar were 95-127, 130-135, and 74-90 kJ mol(-1), respectively and individuals
      were lower for HTC of cellulose than others. Organic acids (acetic acid, formic
      acid, and lactic acid) and phenolic compounds (phenol, catechol, and guaiacol)
      were increasing with higher HTC severity.

PMID- 25063979
TI  - Light piping activates chlorophyll biosynthesis in the under-soil hypocotyl
      section of bean seedlings.
AB  - Protochlorophyllide (Pchlide), protochlorophyll (Pchl) and chlorophyll (Chl)
      contents, their distribution and native arrangements were studied in under-soil
      hypocotyl segments of 4-, 7- and 14-day-old bean (Phaseolus vulgaris L. cv.
      Magnum) seedlings. The plants were grown in general potting soil under natural
      illumination conditions in pots. For sample collection, the pots were transferred
      into dark-room where all manipulations were done under dim green light. The
      pigments were extracted with acetone; phase separation was used to identify the
      Pchl contents. Fluorescence microscopic studies were done and 77K fluorescence
      emission spectra were recorded. Using a special setup of a spectrofluorometer,
      the vertical light piping properties of the above-soil shoots were measured. The
      segments in the 5-7 cm deep soil region contained Pchlide and Pchl in 4- and 7
      day-old seedlings and the segments towards the soil surface contained Chl in
      increasing amounts. In parallel with the pith degradation of hypocotyls, the Chl
      content of elder seedlings increased in the deeper under-soil segments. These
      results prove that the tissue structure of the shoot ensures light piping thus
      greening process and chloroplast formation can take place even in under-soil
      organs not directly exposed to light.

PMID- 25063980
TI  - Vitamin B12 deficiency is associated with geographical latitude and solar
      radiation in the older population.
AB  - BACKGROUND: Vitamin B12 and folic acid deficiency are common in the older and are
      associated with several conditions including anaemia, cardiovascular disease,
      cognitive impairment and cancer. Evidence from in vitro studies suggests that
      solar radiation can degrade both vitamins in the skin. Chile is the longest
      country in the world running perfectly North-South making it an ideal place to
      study potential associations of latitude and solar radiation on vitamin B12 and
      folic acid deficiency. OBJECTIVES: The objective was to examine the association
      between vitamin B12 and folic acid deficiencies and latitude. METHODS: Plasma
      samples were collected from Chileans aged 65+ years (n=1013) living across the
      whole country and assayed for vitamin B12 and folic acid concentrations as part
      of the Chilean Health Survey 2009-2010, which is a national representative sample
      study. RESULTS: Overall, the prevalence of vitamin B12 deficiency was 11.3%, with
      the prevalence in the North of the country being significantly greater than in
      the Central and South zones (19.1%,10.5%, and 5.7%, respectively; P<0.001). The
      prevalence of folic acid deficiency in the whole cohort was 0.7% with no
      difference between the 3 geographical zones. Using logistic regression analyses,
      vitamin B12 deficiency was significantly associated with geographical latitude
      (OR 0.910 [95% confidence intervals 0.890-0.940], P<0.001) and solar radiation
      (OR 1.203 [95% confidence intervals 1.119-1.294], P<<0.001). These associations
      persisted after adjustments for confounders (OR 0.930, P<0.001 and 1.198,
      P=0.002, respectively). CONCLUSIONS: In the Chilean population of 65+, the
      prevalence of vitamin B12 deficiency is associated with living closer to the
      Equator and solar radiation. Although degradation by solar radiation might
      explain this observation, further work is required to establish the potential
      mechanisms. In countries that routinely fortify food with folic acid, efforts to
      identify vitamin B12 deficiency might be more cost-efficiently targeted in areas
      closest to the Equator.

PMID- 25063981
TI  - Knowledge, attitude and practice regarding solar ultraviolet exposure among
      medical university students in Northeast China.
AB  - To assess the knowledge, attitudes and practices regarding the health effects of
      ultraviolet radiation (UVR) and sun exposure among medical university students in
      Northeast China, 385 subjects were investigated on October 2013 using a self
      administered multiple-choice questionnaire. Most of the subjects knew the effects
      of UVR on skin cancer (95.6%) and sunburn (92.2%), but fewer knew of the eye
      damage that can result from UVR (27.8% cataract and 3.1% pterygium).
      Correspondingly, the main purpose of adopting sun protection was considered to be
      'preventing sunburn' (55.4%), but 'preventing eye damage' was the least (1.8%).
      In actual behaviour, the eyes received the least protection as well. Although
      knowing the effects of UVR on vitamin D synthesis (87.3%), 66.8% of participants
      never or seldom increased sun exposure. Compared to men, women were more likely
      to reduce sun exposure (P<0.001). Only a small fraction of subjects (6.6%)
      thought that tanning was attractive. Considering the response variability to UVR
      in people with different skin colours, different sun protection programs should
      be provided. In China, especially in the North, the public should be educated to
      moderately increase sun exposure to maintain adequate vitamin D status while also
      protecting against eye damage from UVR. 

PMID- 25063982
TI  - Synthesis, spectral, structural analysis and biological evaluation of a new
      hydrogen-bonded charge-transfer complex: 2,3-dimethylquinoxalinium-p
      toluenesulfonate.
AB  - Studies concentration on hydrogen-bonded charge-transfer complex formed on the
      reaction between basic 2,3-dimethylquinoxaline with p-toluenesulfonic acid. The
      crystal was characterized by IR, NMR, thermal and elemental analysis. The crystal
      structure was deduced by single crystal X-ray diffraction studies which indicated
      that cation and anion are linked through strong N(+)-H---O(-) type of hydrogen
      bond. The hydrogen bonded charge transfer crystal was screened for its
      pharmacology, such as Calf thymus DNA binding/cleavage, antioxidant properties.
      The results indicated that the compound could interact with DNA through
      intercalation and should have weak to moderate capacity of scavenging with DPPH.
      The high thermal stability is due to the molecular frame work through H-bonding
      interaction. The microbial activities of synthesised compound were examined
      against various bacteria and fungi species. 

PMID- 25063983
TI  - Esculetin and esculin (esculetin 6-O-glucoside) occur as inclusions and are
      differentially distributed in the vacuole of palisade cells in Fraxinus ornus
      leaves: a fluorescence microscopy analysis.
AB  - The location of individual coumarins in leaves of Fraxinus ornus acclimated at
      full solar irradiance was estimated using their specific UV- and fluorescence
      spectral features. Using a combination of UV-induced fluorescence and blue light
      induced fluorescence of tissues stained with diphenylborinic acid 2-amino
      ethylester, in wide field or confocal laser scanning microscopy, we were able to
      visualize the distribution of esculetin and esculetin 6-O-glucoside (esculin) in
      palisade cells. Coumarins are not uniformly distributed in the cell vacuole, but
      accumulate mostly in the adaxial portion of palisade cells. Our study indeed
      shows, for the first time, that coumarins in palisade cells accumulate as
      vacuolar inclusions, as previously reported in the pertinent literature only for
      anthocyanins. Furthermore, esculetin and esculin have a different vacuolar
      distribution: esculetin largely predominates in the first 15 MUm from the adaxial
      epidermis. This leads to hypothesize for esculetin and esculin different
      transport mechanisms from the endoplasmic reticulum to the vacuole as well as
      potentially different roles in photoprotection. Our study open to new experiments
      aimed at exploring the mechanisms that deliver coumarins to the vacuole using
      different fluorescence signatures of coumarin aglycones and coumarin glycosides.

PMID- 25063984
TI  - Multi-scale engineering of plant cell cultures for promotion of specialized
      metabolism.
AB  - To establish plant culture systems for product synthesis, a multi-scale
      engineering approach is necessary. At the intracellular level, the influx of
      'omics' data has necessitated development of new methods to properly annotate and
      establish useful metabolic models that can be applied to elucidate unknown steps
      in specialized metabolite biosynthesis, define effective metabolic engineering
      strategies and increase enzyme diversity available for synthetic biology
      platforms. On an intercellular level, the presence of aggregates in culture leads
      to distinct metabolic sub-populations. Recent advances in flow cytometric
      analyses and mass spectrometry imaging allow for resolution of metabolites on the
      single cell level, providing an increased understanding of culture heterogeneity.
      Finally, extracellular engineering can be used to enhance culture performance
      through media manipulation, co-culture with bacteria, the use of exogenous
      elicitors or modulation of shear stress. 

PMID- 25063985
TI  - Prenatal meditation influences infant behaviors.
AB  - Meditation is important in facilitating health. Pregnancy health has been shown
      to have significant consequences for infant behaviors. In view of limited studies
      on meditation and infant temperament, this study aims to explore the effects of
      prenatal meditation on these aspects. The conceptual framework was based on the
      postulation of positive relationships between prenatal meditation and infant
      health. A randomized control quantitative study was carried out at Obstetric
      Unit, Queen Elizabeth Hospital in Hong Kong. 64 pregnant Chinese women were
      recruited for intervention and 59 were for control. Outcome measures were cord
      blood cortisol, infant salivary cortisol, and Carey Infant Temperament
      Questionnaire. Cord blood cortisol level of babies was higher in the intervention
      group (p<0.01) indicates positive health status of the newborns verifies that
      prenatal meditation can influence fetal health. Carey Infant Temperament
      Questionnaire showed that the infants of intervention group have better
      temperament (p<0.05) at fifth month reflects the importance of prenatal
      meditation in relation to child health. Present study concludes the positive
      effects of prenatal meditation on infant behaviors and recommends that pregnancy
      care providers should provide prenatal meditation to pregnant women. 

PMID- 25063987
TI  - Using exercises to improve public health preparedness in Asia, the Middle East
      and Africa.
AB  - BACKGROUND: Exercises are increasingly common tools used by the health sector and
      other sectors to evaluate their preparedness to respond to public health threats.
      Exercises provide an opportunity for multiple sectors to practice, test and
      evaluate their response to all types of public health emergencies. The
      information from these exercises can be used to refine and improve preparedness
      plans. There is a growing body of literature about the use of exercises among
      local, state and federal public health agencies in the United States. There is
      much less information about the use of exercises among public health agencies in
      other countries and the use of exercises that involve multiple countries.
      RESULTS: We developed and conducted 12 exercises (four sub-national, five
      national, three sub-regional) from August 2006 through December 2008. These 12
      exercises included 558 participants (average 47) and 137 observers (average 11)
      from 14 countries. Participants consistently rated the overall quality of the
      exercises as very good or excellent. They rated the exercises lowest on their
      ability to identifying key gaps in performance. The vast majority of participants
      noted that they would use the information they gained at the exercise to improve
      their organization's preparedness to respond to an influenza pandemic.
      Participants felt the exercises were particularly good at raising awareness and
      understanding about public health threats, assisting in evaluating plans and
      identifying priorities for improvement, and building relationships that
      strengthen preparedness and response across sectors and across countries.
      Participants left the exercises with specific ideas about the most important
      actions that they should engage in after the exercise such as improved planning
      coordination across sectors and countries and better training of health workers
      and response personnel. CONCLUSIONS: These experiences suggest that exercises can
      be a valuable, low-burden tool to improve emergency preparedness and response in
      countries around the world. They also demonstrate that countries can work
      together to develop and conduct successful exercises designed to improve regional
      preparedness to public health threats. The development of standardized evaluation
      methods for exercises may be an additional tool to help focus the actions to be
      taken as a result of the exercise and to improve future exercises. Exercises show
      great promise as tools to improve public health preparedness across sectors and
      countries.

PMID- 25063986
TI  - Virus interactions with endothelial cell receptors: implications for viral
      pathogenesis.
AB  - The endothelial lining of the vasculature performs a vital role in maintaining
      fluid barrier functions despite balancing nutrient and fluid content of tissues,
      repairing localized damage, coordinating responses of a plethora of factors,
      immune cells and platelets through a multitude of endothelial cell surface
      receptors. Viruses that nonlytically cause lethal hemorrhagic or edematous
      diseases engage receptors on vascular and lymphatic endothelial cells, altering
      normal cellular responses that control capillary leakage and fluid clearance
      functions with lethal consequences. Recent studies indicate that receptors
      directing dengue virus and hantavirus infection of the endothelium contribute to
      the dysregulation of normal endothelial cell signaling responses that control
      capillary permeability and immune responses that contribute to pathogenesis. Here
      we present recent studies of virally altered endothelial functions that provide
      new insight into targeting barrier functions of the endothelium as a potential
      therapeutic approach. 

PMID- 25063988
TI  - Essential pediatric hypertension: defining the educational needs of primary care
      pediatricians.
AB  - BACKGROUND: In order to better understand the educational needs regarding
      appropriate recognition, diagnosis and management of pediatric hypertension
      (HTN), we asked practicing pediatricians questions regarding their educational
      needs and comfort level on this topic. METHODS: We conducted 4 focus group
      sessions that included 27 participants representing pediatric residents,
      adolescent medicine physicians, clinic based pediatricians and office based
      pediatricians. Each focus group session lasted for approximately an hour and 90
      pages of total transcriptions were produced verbatim from audio recordings.
      RESULTS: Four reviewers read each transcript and themes were elucidated from
      these transcripts. Overall, 5 major themes related to educational needs and
      clinical concerns were found: utilization of resources to define blood pressure
      (BP), correct BP measurement method(s), co-morbidities, barriers to care, and
      experience level with HTN. Six minor themes were also identified: differences in
      BP measurement, accuracy of BP, recognition of HTN, practice pattern of care,
      education of families and patients, and differences in level of training. The
      focus group participants were also questioned on their preferences regarding
      educational methods (i.e. e-learning, small group sessions, self-study, large
      group presentations) and revealed varied teaching and learning preferences.
      CONCLUSIONS: There are multiple methods to approach education regarding pediatric
      HTN for primary care pediatricians based on provider preferences and multiple
      educational activities should be pursued to achieve best outcomes. Based on this
      data, the next direction will be to develop and deliver multiple educational
      methods and to evaluate the impact on practice patterns of care for children and
      adolescents with HTN.

PMID- 25063989
TI  - Utility of susceptibility-weighted imaging and arterial spin perfusion imaging in
      pediatric brain arteriovenous shunting.
AB  - INTRODUCTION: The objectives of the study are to investigate the application of
      susceptibility-weighted imaging (SWI) and arterial spin labeling (ASL) imaging in
      the assessment of shunting and the draining veins in pediatric patients with
      arteriovenous shunting and compare the utility of SWI and ASL with conventional
      MR and digital subtraction angiography (DSA). METHODS: This study is a
      retrospective study of 19 pediatric patients with arteriovenous shunting on brain
      MRI who were also evaluated with DSA. We assessed the ability of conventional MRI
      sequences, susceptibility magnitude images, phase-filtered SWI images, and pulsed
      ASL images in the detection of arteriovenous (AV) shunting, number of draining
      veins and drainage pathways in comparison to DSA. RESULTS: The mean number of
      detected draining veins on DSA (3.63) was significantly higher compared to SWI
      phase-filtered image (mean = 2.72), susceptibility magnitude image (mean = 2.92),
      ASL (mean = 1.76) and conventional MRI (2.47) (p < 0.05). Pairwise comparison of
      DSA difference scores (i.e., difference between MR modalities in the number of
      missed draining veins) revealed no difference between the MR modalities (p >
      0.05). ASL was the only method that correctly identified superficial and deep
      venous drainage in all patients. Regarding detection of shunting, ASL, SWI phase
      filtered, and magnitude images demonstrated shunting in 100, 83, and 84% of
      patients, respectively. CONCLUSION: SWI depicts a higher number of draining vein
      compared to conventional MR pulse sequences. ASL is a sensitive approach in
      showing 100% sensitivity in the detection of AV shunting and in the diagnosis of
      the pattern of venous drainage. The present findings suggest the added utility of
      both SWI and ASL in the assessment of AV shunting.

PMID- 25063990
TI  - EGM Jackpots and Player Behaviour: An In-venue Shadowing Study.
AB  - Although electronic gaming machine (EGM) jackpots are widespread, little research
      has yet considered the impact of this feature on gamblers' behaviour. We present
      the results of an in-venue shadowing study, which provided measures of player
      investment and persistence (e.g. number of spins, time-on-machine) from
      participants undertaking one or more EGM sessions on their choice of machines.
      234 participants (162 female) were recruited in-venue, with half (stratified by
      age and gender) primed by answering questions encouraging 'big-win' oriented
      ideation. Primed participants were more likely to select jackpot-oriented EGMs,
      and primed at-risk [Problem Gambling Severity Index (PGSI) > 4] gamblers tended
      to select machines with a higher median jackpot prize amount than others
      ([Formula: see text]). Neither PGSI nor priming was associated with the rate at
      which participants switched machines. EGM jackpots were associated with great
      spend overall, and PGSI score was associated with a greater spend per play.
      Positive interactions were found between jackpots and PGSI, and PGSI and priming
      in terms of predicting greater persistence. Finally a structural model of session
      level variables is presented, that incorporates positive feedback between money
      won and number of plays in an EGM session. 

PMID- 25063991
TI  - HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the
      mitochondrial permeability transition pore.
AB  - AIMS: Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tolerance
      against acute myocardial ischaemia-reperfusion injury (IRI). However, the
      mechanism through which HIF-1 stabilization actually confers this
      cardioprotection is not clear. We investigated whether HIF-1alpha stabilization
      protects the heart against acute IRI by preventing the opening of the
      mitochondrial permeability transition pore (MPTP) and the potential mechanisms
      involved. METHODS AND RESULTS: Stabilization of myocardial HIF-1 was achieved by
      pharmacological inhibition of prolyl hydroxylase (PHD) domain-containing enzyme
      using GSK360A or using cardiac-specific ablation of von Hippel-Lindau protein
      (VHL(fl/fl)) in mice. Treatment of HL-1 cardiac cells with GSK360A stabilized HIF
      1, increased the expression of HIF-1 target genes pyruvate dehydrogenase kinase-1
      (PDK1) and hexokinase II (HKII), and reprogrammed cell metabolism to aerobic
      glycolysis, thereby resulting in the production of less mitochondrial oxidative
      stress during IRI, and less MPTP opening, effects which were shown to be
      dependent on HKII. These findings were further confirmed when HIF-1 stabilization
      in the rat and murine heart resulted in smaller myocardial infarct sizes (both in
      vivo and ex vivo), decreased mitochondrial oxidative stress, and inhibited MPTP
      opening following IRI, effects which were also found to be dependent on HKII.
      CONCLUSIONS: We have demonstrated that acute HIF-1alpha stabilization using
      either a pharmacological or genetic approach protected the heart against acute
      IRI by promoting aerobic glycolysis, decreasing mitochondrial oxidative stress,
      activating HKII, and inhibiting MPTP opening.

PMID- 25063992
TI  - Alcohol screening and brief interventions for offenders in the probation setting
      (SIPS Trial): a pragmatic multicentre cluster randomized controlled trial.
AB  - AIM: To evaluate the effectiveness of different brief intervention strategies at
      reducing hazardous or harmful drinking in the probation setting. Offender
      managers were randomized to three interventions, each of which built on the
      previous one: feedback on screening outcome and a client information leaflet
      control group, 5 min of structured brief advice and 20 min of brief lifestyle
      counselling. METHODS: A pragmatic multicentre factorial cluster randomized
      controlled trial. The primary outcome was self-reported hazardous or harmful
      drinking status measured by Alcohol Use Disorders Identification Test (AUDIT) at
      6 months (negative status was a score of <8). Secondary outcomes were AUDIT
      status at 12 months, experience of alcohol-related problems, health utility,
      service utilization, readiness to change and reduction in conviction rates.
      RESULTS: Follow-up rates were 68% at 6 months and 60% at 12 months. At both time
      points, there was no significant advantage of more intensive interventions
      compared with the control group in terms of AUDIT status. Those in the brief
      advice and brief lifestyle counselling intervention groups were statistically
      significantly less likely to reoffend (36 and 38%, respectively) than those in
      the client information leaflet group (50%) in the year following intervention.
      CONCLUSION: Brief advice or brief lifestyle counselling provided no additional
      benefit in reducing hazardous or harmful drinking compared with feedback on
      screening outcome and a client information leaflet. The impact of more intensive
      brief intervention on reoffending warrants further research.

PMID- 25063993
TI  - Solution NMR structures of Pyrenophora tritici-repentis ToxB and its inactive
      homolog reveal potential determinants of toxin activity.
AB  - Pyrenophora tritici-repentis Ptr ToxB (ToxB) is a proteinaceous host-selective
      toxin produced by Pyrenophora tritici-repentis (P. tritici-repentis), a plant
      pathogenic fungus that causes the disease tan spot of wheat. One feature that
      distinguishes ToxB from other host-selective toxins is that it has naturally
      occurring homologs in non-pathogenic P. tritici-repentis isolates that lack toxic
      activity. There are no high-resolution structures for any of the ToxB homologs,
      or for any protein with >30% sequence identity, and therefore what underlies
      activity remains an open question. Here, we present the NMR structures of ToxB
      and its inactive homolog Ptr toxb. Both proteins adopt a beta-sandwich fold
      comprising three strands in each half that are bridged together by two disulfide
      bonds. The inactive toxb, however, shows higher flexibility localized to the
      sequence-divergent beta-sandwich half. The absence of toxic activity is
      attributed to a more open structure in the vicinity of one disulfide bond, higher
      flexibility, and residue differences in an exposed loop that likely impacts
      interaction with putative targets. We propose that activity is regulated by
      perturbations in a putative active site loop and changes in dynamics distant from
      the site of activity. Interestingly, the new structures identify AvrPiz-t, a
      secreted avirulence protein produced by the rice blast fungus, as a structural
      homolog to ToxB. This homology suggests that fungal proteins involved in either
      disease susceptibility such as ToxB or resistance such as AvrPiz-t may have a
      common evolutionary origin. 

PMID- 25063995
TI  - Reply to: differentiation between KPC and IMP carbapenemase need phenotypic and
      genotypic methods.

PMID- 25063994
TI  - Describing the genetic architecture of epilepsy through heritability analysis.
AB  - Epilepsy is a disease with substantial missing heritability; despite its high
      genetic component, genetic association studies have had limited success detecting
      common variants which influence susceptibility. In this paper, we reassess the
      role of common variants on epilepsy using extensions of heritability analysis.
      Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal
      epilepsy, and 5129 population control subjects, with genotypes recorded for over
      4 million common single nucleotide polymorphisms. Firstly, we show that on the
      liability scale, common variants collectively explain at least 26% (standard
      deviation 5%) of phenotypic variation for all epilepsy and 27% (standard
      deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating
      the number of causal variants for complex traits; when applied to epilepsy, our
      most optimistic estimate suggests that at least 400 variants influence disease
      susceptibility, with potentially many thousands. Thirdly, we use bivariate
      analysis to assess how similar the genetic architecture of focal epilepsy is to
      that of non-focal epilepsy; we demonstrate both significant differences (P =
      0.004) and significant similarities (P = 0.01) between the two subtypes,
      indicating that although the clinical definition of focal epilepsy does identify
      a genetically distinct epilepsy subtype, there is also scope to improve the
      classification of epilepsy by incorporating genotypic information. Lastly, we
      investigate the potential value in using genetic data to diagnose epilepsy
      following a single epileptic seizure; we find that a prediction model explaining
      10% of phenotypic variation could have clinical utility for deciding which single
      seizure individuals are likely to benefit from immediate anti-epileptic drug
      therapy.

PMID- 25063996
TI  - Probability of pregnancy after sterilization: a comparison of hysteroscopic
      versus laparoscopic sterilization.

PMID- 25063997
TI  - Use of Cognitive Work Analysis for exploration of safety management in the
      operation of motorcycles and scooters.
AB  - The risk of accident, injury and death is disproportionately higher for
      motorcycle riders than for motorists. In this paper, we investigate strategies of
      safety management associated with operation of powered two-wheel vehicles
      (motorcycles and scooters). Accident prevention is most often driven by an
      epidemiological approach that investigates the risk factors associated with
      accidents. By focusing on risk factors, these types of studies fail to examine
      the strengths of the system in any depth. In this paper we employ an ethnographic
      approach structured by reference to the framework of Cognitive Work Analysis, to
      identify how riders of powered two-wheel vehicles manage their own safety and the
      safety of others. We anticipate that this research will open up a rich,
      relatively untapped, area for exploration of safety interventions. 

PMID- 25063998
TI  - Does walkable neighbourhood design influence the association between objective
      crime and walking?
AB  - BACKGROUND: Few studies have investigated associations between objectively
      measured crime and walking, and findings are mixed. One explanation for null or
      counterintuitive findings emerges from criminology studies, which indicate that
      the permeable street layouts and non-residential land uses that underpin walkable
      neighbourhoods are also associated with more crime. This study examined
      associations between objective crime and walking, controlling for the
      characteristics of walkable neighbourhoods. METHODS: A population representative
      sample of adults (25-65 years) (n = 3,487) completed the Western Australian
      Health and Wellbeing Survey (2006-2008) demographic and walking frequency items.
      Objective environmental measures were generated for each participant's 400 m and
      1600 m neighbourhood areas, including burglary, personal crime (i.e., crimes
      committed against people) in public space, residential density, street
      connectivity and local destinations. Log-linear negative binomial regression
      models were used to examine associations between crime and walking
      frequency/week, with progressive adjustment for residential density, street
      connectivity and local destinations. RESULTS: Burglary and personal crime
      occurring within a participant's 400 m and 1600 m neighbourhoods were positively
      and significantly associated with walking frequency. For example, for every
      additional 10 crimes against the person/year within 400 m of a participant's
      home, walking frequency increased by 8% (relative change = 1.077, p = 0.017).
      Associations remained constant after controlling for residential density and
      street connectivity, but attenuated after adjusting for local destinations (e.g.,
      for personal crime in 400 m: relative change = 1.054, p = 0.104). This pattern of
      attenuation was evident across both crime categories and both neighbourhood
      sizes. CONCLUSIONS: The observed positive associations between objective crime
      and walking appear to be a function of living in a more walkable environment, as
      the presence of destinations has the capacity to both promote walking and attract
      crime. This study provides a plausible explanation for some mixed findings
      emerging from studies examining crime as a barrier to walking. In some settings,
      the hypothesised deterrent effect of crime on walking may be insufficient to
      outweigh the positive impacts of living in a more walkable environment.

PMID- 25063999
TI  - A bioactive "self-fitting" shape memory polymer scaffold with potential to treat
      cranio-maxillo facial bone defects.
AB  - While tissue engineering is a promising alternative for treating critical-sized
      cranio-maxillofacial bone defects, improvements in scaffold design are needed. In
      particular, scaffolds that can precisely match the irregular boundaries of bone
      defects as well as exhibit an interconnected pore morphology and bioactivity
      would enhance tissue regeneration. In this study, a shape memory polymer (SMP)
      scaffold was developed exhibiting an open porous structure and the capacity to
      conformally "self-fit" into irregular defects. The SMP scaffold was prepared via
      photocrosslinking of poly(epsilon-caprolactone) (PCL) diacrylate using a SCPL
      method, which included a fused salt template. A bioactive polydopamine coating
      was applied to coat the pore walls. Following exposure to warm saline at
      T>T(trans) (T(trans)=T(m) of PCL), the scaffold became malleable and could be
      pressed into an irregular model defect. Cooling caused the scaffold to lock in
      its temporary shape within the defect. The polydopamine coating did not alter the
      physical properties of the scaffold. However, polydopamine-coated scaffolds
      exhibited superior bioactivity (i.e. formation of hydroxyapatite in vitro),
      osteoblast adhesion, proliferation, osteogenic gene expression and extracellular
      matrix deposition.

PMID- 25064000
TI  - Coherent anti-Stokes Raman scattering microscopy driving the future of loaded
      mesoporous silica imaging.
AB  - This study reports the use of variants of coherent anti-Stokes Raman scattering
      (CARS) microscopy as a novel method for improved physicochemical characterization
      of drug-loaded silica particles. Ordered mesoporous silica is a biomaterial that
      can be loaded to carry a number of biochemicals, including poorly water-soluble
      drugs, by allowing the incorporation of drug into nanometer-sized pores. In this
      work, the loading of two poorly water-soluble model drugs, itraconazole and
      griseofulvin, in MCM-41 silica microparticles is characterized qualitatively,
      using the novel approach of CARS microscopy, which has advantages over other
      analytical approaches used to date and is non-destructive, rapid, label free,
      confocal and has chemical and physical specificity. The study investigated the
      effect of two solvent-based loading methods, namely immersion and rotary
      evaporation, and microparticle size on the three-dimensional (3-D) distribution
      of the two loaded drugs. Additionally, hyperspectral CARS microscopy was used to
      confirm the amorphous nature of the loaded drugs. Z-stacked CARS microscopy
      suggested that the drug, but not the loading method or particle size range,
      affected 3-D drug distribution. Hyperspectral CARS confirmed that the drug loaded
      in the MCM-41 silica microparticles was in an amorphous form. The results show
      that CARS microscopy and hyperspectral CARS microscopy can be used to provide
      further insights into the structural nature of loaded mesoporous silica
      microparticles as biomaterials. 

PMID- 25064001
TI  - The effect of heating rate on the surface chemistry of NiTi.
AB  - The impact of the heating rate on the Ni content at the surface of the oxide
      layer of biomedical NiTi is explored. Heat treatment emulating common shape
      setting procedures was performed by means of conventional and inductive heating
      for similar annealing time and temperature, applying various heating rates from
      ~0.25 K s(-1) to 250 K s(-1). A glow discharge optical emission spectroscopy
      method was established and employed to evaluate concentration profiles of Ni, Ti
      and O in the near-surface region at high resolution. The Ni content at the
      surface of the differently treated samples varies significantly, with maximum
      surface Ni concentrations of ~20 at.% at the lowest and ~1.5 at.% at the highest
      heating rate, i.e. the total amount of Ni contained in the surface region of the
      oxide layer decreases by >15 times. Consequently, the heating rate is a
      determinant for the biomedical characteristics of NiTi, especially since Ni
      available at the surface of the oxide layer may affect the hemocompatibility and
      be released promptly after surgical application of a respective implant.
      Furthermore, apparently contradictory results presented in the literature
      reporting surface Ni concentrations of ~3 at.% to >20 at.% after heat treatment
      are consistently explained considering the ascertained effect of the heating
      rate.

PMID- 25064002
TI  - Reply: regional pooling of national data from a small number of sites can be
      misleading: maybe yes? But data can be complimentary to other studies and
      valuable to infectious disease physicians!

PMID- 25064003
TI  - ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?
AB  - BACKGROUND: Dysregulations in cholesterol and lipid metabolism have been linked
      to human diseases like hypercholesterolemia, atherosclerosis or the metabolic
      syndrome. Many ABC transporters are involved in trafficking of metabolites
      derived from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal
      recessive disease caused by ABCC6 mutations, is characterized by atherogenesis
      and soft tissue calcification. METHODS: In this study we investigated the
      regulation of cholesterol biosynthesis in human dermal fibroblasts from PXE
      patients and healthy controls. RESULTS: Gene expression analysis of 84 targets
      indicated dysregulations in cholesterol metabolism in PXE fibroblasts. Transcript
      levels of ABCC6 were strongly increased in lipoprotein-deficient serum (LPDS) and
      under serum starvation in healthy controls. For the first time, increased HMG CoA
      reductase activities were found in PXE fibroblasts. We further observed strongly
      elevated transcript and protein levels for the proprotein convertase
      subtilisin/kexin type 9 (PCSK9), as well as a significant reduction in APOE mRNA
      expression in PXE. CONCLUSION: Increased cholesterol biosynthesis, elevated PCSK9
      levels and reduced APOE mRNA expression newly found in PXE fibroblasts could
      enforce atherogenesis and cardiovascular risk in PXE patients. Moreover, the
      increase in ABCC6 expression accompanied by the induction of cholesterol
      biosynthesis supposes a functional role for ABCC6 in human lipoprotein and
      cholesterol homeostasis.

PMID- 25064004
TI  - Kirschner wire-guided technique for inserting a second needle into inadequately
      filled vertebrae in vertebroplasty: a technical report.
AB  - BACKGROUND CONTEXT: Absence or inadequate filling of cement in the fractured
      vertebrae can cause unsatisfactory results in a vertebroplasty. Repeated needle
      insertion can reduce the incidence of recollapse at the cemented vertebrae.
      However, when inserting the second needle in the usual method, it takes the same
      time and radiation exposure as the first needle. PURPOSE: To report a Kirschner
      wire-guided technique for inserting a second needle into inadequately filled
      vertebrae in vertebroplasty that can make the procedure simple, effective, and,
      most importantly, reduce the radiation exposure. STUDY DESIGN: Description of a
      modified surgical technique with retrospective data analysis. PATIENT SAMPLE:
      From January 2012 to December 2012, 87 percutaneous vertebroplasties were
      performed in our department to treat painful osteoporotic compression fractures.
      Seven adult patients (five women, two men; mean age: 75.7 years) had inadequate
      cement filling in the treated vertebrae that required the insertion of a second
      needle. OUTCOME MEASURES: Back pain was measured using the visual analog scale
      (VAS). The post-vertebroplasty anterior vertebral height and local kyphotic angle
      were used as the radiologic parameters. Intraoperative procedure time and
      fluoroscopy shots and postoperative complication were also evaluated. METHODS:
      The stylus of the first needle was inserted into the trocar to push the cement
      out of the trocar. The stylus was removed, a small diameter K-wire was inserted
      into the trocar, and the trocar was then removed. A second (new) trocar was
      inserted into the vertebral body following the track of the K-wire. When the new
      trocar reached the posterior 1/4 of the vertebral body, the K-wire was removed,
      the stylus was inserted, and the new needle was advanced to the anterior third of
      the vertebra. Cement was then injected into the new area until the filling was
      adequate. RESULTS: The immediate post-vertebroplasty anterior vertebral height
      was 23.31+/-1.95 mm, changed to 22.20+/-3.72 mm at final follow-up. The VAS
      decreased from a mean of 8.4 before vertebroplasty to 1.6 at the final follow-up.
      The follow-up duration ranged from 6 to 15 months (mean 12.6 months). There was
      no case of recollapse of the cemented vertebrae and no procedure-related
      complications. The procedure time of historical controls was 153.5 seconds, which
      reduced to 47.9 seconds by using this technique. The fluoroscopy shots of
      historical controls were 9.7 shots, which reduced to 2 shots by using this
      technique. CONCLUSIONS: This report suggests that Kirschner wire-guided technique
      for inserting a second needle during vertebroplasty could make the procedure
      simple, effective, and, most importantly, reduce the procedure time and radiation
      exposure.

PMID- 25064005
TI  - Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple
      signs of activation in all retinal layers.
AB  - BACKGROUND: Glaucomatous optic neuropathy, a leading cause of blindness, can
      progress despite control of intraocular pressure - currently the main risk factor
      and target for treatment. Glaucoma progression shares mechanisms with
      neurodegenerative disease, including microglia activation. In the present model
      of ocular hypertension (OHT), we have recently described morphological signs of
      retinal microglia activation and MHC-II upregulation in both the untreated
      contralateral eyes and OHT eyes. By using immunostaining, we sought to analyze
      and quantify additional signs of microglia activation and differences depending
      on the retinal layer. METHODS: Two groups of adult Swiss mice were used: age
      matched control (naive, n = 12), and lasered (n = 12). In the lasered animals,
      both OHT eyes and contralateral eyes were analyzed. Retinal whole-mounts were
      immunostained with antibodies against Iba-1, MHC-II, CD68, CD86, and Ym1. The Iba
      1+ cell number in the plexiform layers (PL) and the photoreceptor outer segment
      (OS), Iba-1+ arbor area in the PL, and area of the retina occupied by Iba-1+
      cells in the nerve fiber layer-ganglion cell layer (NFL-GCL) were quantified.
      RESULTS: The main findings in contralateral eyes and OHT eyes were: i) ameboid
      microglia in the NFL-GCL and OS; ii) the retraction of processes in all retinal
      layers; iii) a higher level of branching in PL and in the OS; iv) soma
      displacement to the nearest cell layers in the PL and OS; v) the reorientation of
      processes in the OS; vi) MHC-II upregulation in all retinal layers; vii)
      increased CD68 immunostaining; and viii) CD86 immunolabeling in ameboid cells. In
      comparison with the control group, a significant increase in the microglial
      number in the PL, OS, and in the area occupied by Iba-1+ cells in the NFL-GCL,
      and significant reduction of the arbor area in the PL. In addition, rounded Iba
      1+ CD86+ cells in the NFL-GCL, OS and Ym1+ cells, and rod-like microglia in the
      NFL-GCL were restricted to OHT eyes. CONCLUSIONS: Several quantitative and
      qualitative signs of microglia activation are detected both in the contralateral
      and OHT eyes. Such activation extended beyond the GCL, involving all retinal
      layers. Differences between the two eyes could help to elucidate glaucoma
      pathophysiology.

PMID- 25064006
TI  - The genome sequence of African rice (Oryza glaberrima) and evidence for
      independent domestication.
AB  - The cultivation of rice in Africa dates back more than 3,000 years.
      Interestingly, African rice is not of the same origin as Asian rice (Oryza sativa
      L.) but rather is an entirely different species (i.e., Oryza glaberrima Steud.).
      Here we present a high-quality assembly and annotation of the O. glaberrima
      genome and detailed analyses of its evolutionary history of domestication and
      selection. Population genomics analyses of 20 O. glaberrima and 94 Oryza barthii
      accessions support the hypothesis that O. glaberrima was domesticated in a single
      region along the Niger river as opposed to noncentric domestication events across
      Africa. We detected evidence for artificial selection at a genome-wide scale, as
      well as with a set of O. glaberrima genes orthologous to O. sativa genes that are
      known to be associated with domestication, thus indicating convergent yet
      independent selection of a common set of genes during two geographically and
      culturally distinct domestication processes. 

PMID- 25064007
TI  - A genome-wide association study identifies susceptibility loci for ossification
      of the posterior longitudinal ligament of the spine.
AB  - Ossification of the posterior longitudinal ligament of the spine (OPLL) is a
      common spinal disorder among the elderly that causes myelopathy and
      radiculopathy. To identify genetic factors for OPLL, we performed a genome-wide
      association study (GWAS) in ~8,000 individuals followed by a replication study
      using an additional ~7,000 individuals. We identified six susceptibility loci for
      OPLL: 20p12.3 (rs2423294: P = 1.10 * 10(-13)), 8q23.1 (rs374810: P = 1.88 * 10(
      13)), 12p11.22 (rs1979679: P = 4.34 * 10(-12)), 12p12.2 (rs11045000: P = 2.95 *
      10(-11)), 8q23.3 (rs13279799: P = 1.28 * 10(-10)) and 6p21.1 (rs927485: P = 9.40
      * 10(-9)). Analyses of gene expression in and around the loci suggested that
      several genes are involved in OPLL etiology through membranous and/or
      endochondral ossification processes. Our results bring new insight to the
      etiology of OPLL. 

PMID- 25064008
TI  - The genome of the stress-tolerant wild tomato species Solanum pennellii.
AB  - Solanum pennellii is a wild tomato species endemic to Andean regions in South
      America, where it has evolved to thrive in arid habitats. Because of its extreme
      stress tolerance and unusual morphology, it is an important donor of germplasm
      for the cultivated tomato Solanum lycopersicum. Introgression lines (ILs) in
      which large genomic regions of S. lycopersicum are replaced with the
      corresponding segments from S. pennellii can show remarkably superior agronomic
      performance. Here we describe a high-quality genome assembly of the parents of
      the IL population. By anchoring the S. pennellii genome to the genetic map, we
      define candidate genes for stress tolerance and provide evidence that
      transposable elements had a role in the evolution of these traits. Our work paves
      a path toward further tomato improvement and for deciphering the mechanisms
      underlying the myriad other agronomic traits that can be improved with S.
      pennellii germplasm. 

PMID- 25064010
TI  - An independent occurrence of the chimeric P450 enzyme CYP337B3 of Helicoverpa
      armigera confers cypermethrin resistance in Pakistan.
AB  - The increasing resistance level of insect pest species is a major concern to
      agriculture worldwide. The cotton bollworm, Helicoverpa armigera, is one of the
      most important pest species due to being highly polyphagous, geographically
      widespread, and resistant towards many chemical classes of insecticides. We
      previously described the mechanism of fenvalerate resistance in Australian
      populations conferred by the chimeric cytochrome P450 monooxygenase CYP337B3,
      which arose by unequal crossing-over between CYP337B1 and CYP337B2. Here, we show
      that this mechanism is also present in the cypermethrin-resistant FSD strain from
      Pakistan. The Pakistani and the Australian CYP337B3 alleles differ by 18
      synonymous and three nonsynonymous SNPs and additionally in the length and
      sequence of the intron. Nevertheless, the activity of both CYP337B3 proteins is
      comparable. We demonstrate that CYP337B3 is capable of metabolizing cypermethrin
      (trans- and especially cis-isomers) to the main metabolite 4'
      hydroxycypermethrin, which exhibits no intrinsic toxicity towards susceptible
      larvae. In a bioassay, CYP337B3 confers a 7-fold resistance towards cypermethrin
      in FSD larvae compared to susceptible larvae from the Australian TWB strain
      lacking CYP337B3. Linkage analysis shows that presence of CYP337B3 accounts for
      most of the cypermethrin resistance in the FSD strain; up-regulation of other
      P450s in FSD plays no detectable role in resistance. The presence or absence of
      CYP337B3 can be easily detected by a simple PCR screen, providing a powerful tool
      to rapidly distinguish resistant from susceptible individuals in the field and to
      determine the geographical distribution of this resistance gene. Our results
      suggest that CYP337B3 evolved twice independently by unequal crossing-over
      between CYP337B2 and two different CYP337B1 alleles. 

PMID- 25064011
TI  - Building a community of practice for sustainability: strengthening learning and
      collective action of Canadian biosphere reserves through a national partnership.
AB  - Deliberation, dialogue and systematic learning are now considered attributes of
      good practice for organizations seeking to advance sustainability. Yet we do not
      know whether organizations that span spatial scales and governance
      responsibilities can establish effective communities of practice to facilitate
      learning and action. The purpose of this paper is to generate a framework that
      specifies actions and processes of a community of practice designed to instill
      collective learning and action strategies across a multi-level, multi-partner
      network. The framework is then used to describe and analyze a partnership among
      practitioners of Canada's 16 UNESCO biosphere reserves, and additional
      researchers and government representatives from across Canada. The framework is a
      cycle of seven action steps, beginning and ending with reflecting on and
      evaluating present practice. It is supported by seven characteristics of
      collaborative environmental management that are used to gauge the success of the
      partnership. Our results show that the partnership successfully built trust,
      established shared norms and common interest, created incentives to participate,
      generated value in information sharing and willingness to engage, demonstrated
      effective flow of information, and provided leadership and facilitation. Key to
      success was the presence of a multi-lingual facilitator who could bridge cultural
      differences across regions and academia-practitioner expectations. The project
      succeeded in establishing common goals, setting mutual expectations and building
      relations of trust and respect, and co-creating knowledge. It is too soon to
      determine whether changes in practices that support sustainability will be
      maintained over the long term and without the help of an outside facilitator. 

PMID- 25064012
TI  - The impact of signing a memorandum of understanding on reproductive health with
      the Ministry of Public Health in Cameroon.
AB  - Health statistics relating to Millennium Development Goals 4 and 5 are poor for
      most low-resource countries. Professional societies can assist governments to
      improve these health indicators. For an effective collaboration, the Society of
      Gynaecologists and Obstetricians Cameroon (SOGOC) and the Ministry of Public
      Health signed a memorandum of understanding on reproductive health. A major
      consequence of this collaboration was the ease of transfer of competence
      associated with SOGOC adopting a monitoring and evaluation role, which has
      improved quality of care. The impact of this collaboration for the Society has
      been significant; SOGOC is recognized as a partner and has an opportunity to play
      a leadership role in issues concerning reproductive health. 

PMID- 25064013
TI  - Demand and supply factors affecting the rising overmedicalization of birth in
      India.
AB  - OBJECTIVE: To understand the interaction between health systems and individual
      factors in determining the probability of a cesarean delivery in India. METHODS:
      In a retrospective study, data from the 2007-2008 District Level Household and
      Facility Survey was used to determine the risk of cesarean delivery in six states
      (Punjab, Delhi, Maharashtra, Andhra Pradesh, Kerala, and Tamil Nadu). Multilevel
      modeling was used to account for district and community effects. RESULTS: After
      controlling for key risk factors, the analysis showed that cesareans were more
      likely at private than public institutions (P<0.001). In terms of demand, higher
      education levels rather than wealth seemed to increase the likelihood of a
      cesarean delivery. District-level effects were significant in almost all states
      (P<0.001), demonstrating the need to control for health system factors.
      CONCLUSION: Supply factors might contribute more to the rise in cesarean delivery
      than does demand. Further research is needed to understand whether the quest for
      increased institutional deliveries in a country with high maternal mortality
      might be compromised by pressures for overmedicalization.

PMID- 25064014
TI  - Mentoring: then and now.

PMID- 25064015
TI  - Commonalities and differences in the spatiotemporal neural dynamics associated
      with automatic attentional shifts induced by gaze and arrows.
AB  - Gaze and arrows automatically trigger attentional shifts. Neuroimaging studies
      have identified a commonality in the spatial distribution of the neural
      activation involved in such attentional shifts. However, it remains unknown
      whether these activations occur with common temporal profiles. To investigate
      this issue, magnetoencephalography (MEG) was used to evaluate neural activation
      involved in attentional shifts induced by gaze and arrows. MEG source
      reconstruction analyses revealed that the superior temporal sulcus and the
      inferior frontal gyrus were commonly activated after 200ms, in response to
      directional versus non-directional cues. Regression analyses further revealed
      that the magnitude of brain activity in these areas and in the bilateral
      occipital cortex was positively related to the effect of attentional shift on
      reaction times under both the gaze and the arrow conditions. The results also
      revealed that some brain regions were activated specifically in response to
      directional versus non-directional gaze or arrow cues at the 350-400ms time
      window. These results suggest that the neural mechanisms underlying attentional
      shifts induced by gaze and arrows share commonalities in their spatial
      distributions and temporal profiles, with some spatial differences at later time
      stages. 

PMID- 25064016
TI  - Modeling the respiratory chain complexes with biothermokinetic equations - the
      case of complex I.
AB  - The mitochondrial respiratory chain plays a crucial role in energy metabolism and
      its dysfunction is implicated in a wide range of human diseases. In order to
      understand the global expression of local mutations in the rate of oxygen
      consumption or in the production of adenosine triphosphate (ATP) it is useful to
      have a mathematical model in which the changes in a given respiratory complex are
      properly modeled. Our aim in this paper is to provide thermodynamics respecting
      and structurally simple equations to represent the kinetics of each isolated
      complexes which can, assembled in a dynamical system, also simulate the behavior
      of the respiratory chain, as a whole, under a large set of different
      physiological and pathological conditions. On the example of the reduced
      nicotinamide adenine dinucleotide (NADH)-ubiquinol-oxidoreductase (complex I) we
      analyze the suitability of different types of rate equations. Based on our
      kinetic experiments we show that very simple rate laws, as those often used in
      many respiratory chain models, fail to describe the kinetic behavior when applied
      to a wide concentration range. This led us to adapt rate equations containing the
      essential parameters of enzyme kinetic, maximal velocities and Henri-Michaelis
      Menten like-constants (KM and KI) to satisfactorily simulate these data. 

PMID- 25064017
TI  - A panel of biomarkers for predicting response to postoperative RT for laryngeal
      cancer?
AB  - OBJECTIVES: Postoperative radiotherapy (PORT) improves locoregional control and
      survival rates for patients with advanced laryngeal carcinoma (LSCC), but
      reported outcomes after PORT for LSCC vary considerably. Predictive markers
      (including biomarkers) are needed for LSCC to orient the choice of the most
      appropriate adjuvant therapy for individual patients. The aim of this study was
      to identify a panel of LSCC tissue markers (considering EGFR, mTOR, survivin, Bcl
      2, angiogenin, endoglin [CD105], nm23-H1) capable of pinpointing patients at
      higher risk of recurrence among 33 LSCC cases treated with PORT. METHODS/RESULTS:
      Univariate analysis found 4 biomarkers (mTOR, nuclear survivin, CD105, non
      nuclear nm23-H1) significantly associated with LSCC recurrence. A collinearity
      emerged between mTOR and CD105 expressions. The predictive role of two different
      panels (panel 1: mTOR, nuclear survivin, non-nuclear nm23-H1; panel 2: CD105,
      nuclear survivin, non-nuclear nm23-H1) was considered. According to the Hosmer
      and Lemeshow scale, panel 1 demonstrated an outstanding discriminatory power (AUC
      0.903) in predicting LSCC recurrence after PORT. Panel 2 had an excellent
      discriminatory power too (AUC 0.899). CONCLUSIONS: Both panels of biomarkers
      showed an important discriminatory power in pinpointing patients at higher risk
      of recurrence after PORT for LSCC who could reasonably benefit from adjuvant
      postoperative chemo-RT.

PMID- 25064018
TI  - Partial lateral patellar facetectomy as an alternative to lateral release in
      Total Knee Arthroplasty (TKA).
AB  - This study presents the selective use of partial patellar lateral facetectomy for
      maltracking during primary TKA, as an alternative to lateral release. Twenty
      three partial facetectomies were performed out of 191 TKAs (12%). Balanced
      tracking was achieved in 22 knees. At follow-up 2 patients had persistent
      anterior knee pain. Mean Knee Society score (KSS) was 94 and mean functional KSS
      was 86. Mean patellar score was 28. Patellar tilt angles were within 2 degrees in
      all but one knee. Patellar translation was within 2 mm in all cases. No
      complications were recorded. A control group of 46 matched patients had similar
      functional and radiographic results. If tracking is not satisfactory at the
      conclusion of TKA, our method of choice would be partial lateral facetectomy. 

PMID- 25064019
TI  - Use of continuous transdermal alcohol monitoring during a contingency management
      procedure to reduce excessive alcohol use.
AB  - BACKGROUND: Research on contingency management to treat excessive alcohol use is
      limited due to feasibility issues with monitoring adherence. This study examined
      the effectiveness of using transdermal alcohol monitoring as a continuous measure
      of alcohol use to implement financial contingencies to reduce heavy drinking.
      METHODS: Twenty-six male and female drinkers (from 21 to 39 years old) were
      recruited from the community. Participants were randomly assigned to one of the
      two treatment sequences. Sequence 1 received 4 weeks of no financial contingency
      (i.e., $0) drinking followed by 4 weeks each of $25 and then $50 contingency
      management; Sequence 2 received 4 weeks of $25 contingency management followed by
      4 weeks each of no contingency (i.e., $0) and then $50 contingency management.
      During the $25 and $50 contingency management conditions, participants were paid
      each week when the Secure Continuous Remote Alcohol Monitor (SCRAM-IITM)
      identified no heavy drinking days. RESULTS: Participants in both contingency
      management conditions had fewer drinking episodes and reduced frequencies of
      heavy drinking compared to the $0 condition. Participants randomized to Sequence
      2 (receiving $25 contingency before the $0 condition) exhibited less frequent
      drinking and less heavy drinking in the $0 condition compared to participants
      from Sequence 1. CONCLUSIONS: Transdermal alcohol monitoring can be used to
      implement contingency management programs to reduce excessive alcohol
      consumption.

PMID- 25064020
TI  - Serum brain-derived neurotrophic factor and nerve growth factor decreased in
      chronic ketamine abusers.
AB  - AIMS: This study investigated the serum levels of brain-derived neurotrophic
      factor (BDNF) and nerve growth factor (NGF) in a group of chronic ketamine
      abusers in comparison to healthy controls. The correlations between the serum
      BDNF, NGF level with the subjects' demographic, pattern of ketamine use were also
      examined. METHODS: 93 subjects who met the criteria of ketamine dependence and 39
      healthy subjects were recruited. Serum BDNF and NGF levels were assayed by enzyme
      linked immunosorbent assay (ELISA). Psychopathological symptoms were assessed
      using Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory
      (BDI) and Beck Anxiety Inventory (BAI). RESULTS: Both serum levels of BDNF and
      NGF were significant lower in the ketamine users compared to the healthy control
      subjects (9.50+/-6.68 versus 14.37+/-6.07 ng/ml, p=0.019 for BDNF; 1.93+/-0.80
      versus 2.60+/-1.07 ng/ml, p=0.011 for NGF). BDNF level was negatively associated
      with current frequency of ketamine use (r=-0.209, p=0.045). CONCLUSIONS: Both
      BDNF and NGF serum concentrations were significantly lower among chronic ketamine
      users than among health controls.

PMID- 25064021
TI  - A meta-analysis of ear-acupuncture, ear-acupressure and auriculotherapy for
      cigarette smoking cessation.
AB  - BACKGROUND: This systematic review evaluated the effects of ear acupuncture, ear
      acupressure and auriculotherapy for cigarette smoking cessation (SC) at end-of
      treatment (EoT), three, six and 12 months follow-up. METHODS: Searches of six
      English and Chinese databases located 25 randomized controlled trials (3735
      participants). Methodological quality was assessed using Cochrane Risk of Bias.
      Meta-analyses were conducted in two pools: 1. SC-specific ear
      acupuncture/acupressure or auriculotherapy (EAP/R) vs. non-specific/inactive
      control; and 2. SC-specific EAP/R vs. other SC-specific treatment. Sensitivity
      analyses were conducted based on the validity of interventions as SC-specific
      treatments or non-specific/inactive interventions; and the use of biochemical SC
      confirmation. RESULTS: Pool 1: the 12 valid SC-specific EAP/R interventions were
      superior to inactive EAP/R controls at EoT (RR=1.77 [1.39, 2.25]), three months
      follow-up (RR=1.54 [1.14, 2.08]), and six months follow-up (RR=2.01, [1.23,
      3.28]) but data were insufficient at 12 months. In Pool 2: there was no
      superiority or inferiority for EAP/R at EoT or at 3 and 6 month follow-ups
      compared to SC-specific behavioural therapy or SC-specific body acupuncture.
      CONCLUSIONS: Pool 1 data appeared most consistent for studies of ear acupressure
      (EAPR) vs. non-specific EAPR controls, with confirmed SC rates at 3 months post
      treatment of 20.0% for test groups vs. 7.5% for controls. In Pool 2 the EAP/R
      interventions appeared neither inferior nor superior to the behavioural
      interventions at 3 and 6 month follow-ups. However, meta-analysis results derived
      from relatively small-sized trials with no biochemical validation of SC in Pool
      2. Larger, well-controlled studies using biochemical confirmation of SC are
      needed.

PMID- 25064022
TI  - Adverse childhood experiences and interaction with methamphetamine use frequency
      in the risk of methamphetamine-associated psychosis.
AB  - BACKGROUND: This study aims to examine adverse childhood experiences (ACEs), its
      interaction with methamphetamine (METH) use (e.g., frequency, duration, and
      dependence) and METH-associated risk of psychosis. METHODS: This was a cross
      sectional study conducted among METH users at a drug rehabilitation center in
      China. Participants were assessed using Mini International Neuropsychiatric
      Interview for METH-associated psychosis. RESULTS: Of 189 participants, 50.5%
      reported at least one of eight ACE categories and 35.4% had past history of a
      psychotic episode. After adjusting for age, sex, education, and marital status,
      all ACE categories except emotional abuse and parental separation or divorce
      increased the risk of ever experiencing METH-associated psychosis. When comparing
      participants who reported no ACEs, those with three or more ACEs had higher risks
      of lifetime psychosis (OR=4.5, 95% CI: 1.6-12.6). Relationship between number of
      ACEs and lifetime psychosis was graded (p<.01). The interaction between frequency
      of METH use (>=4 vs. <4 times/month) and number of ACEs on the risk of METH
      associated psychosis was statistically significant (p=0.02), showing a trend of
      adjusted OR decreased significantly as the number of ACEs increased. CONCLUSIONS:
      These analyses indicate that childhood adversities increase the individual's
      vulnerability to METH-associated psychosis. Further larger longitudinal studies
      are warranted.

PMID- 25064009
TI  - Large-scale meta-analysis of genome-wide association data identifies six new risk
      loci for Parkinson's disease.
AB  - We conducted a meta-analysis of Parkinson's disease genome-wide association
      studies using a common set of 7,893,274 variants across 13,708 cases and 95,282
      controls. Twenty-six loci were identified as having genome-wide significant
      association; these and 6 additional previously reported loci were then tested in
      an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24
      replicated, including 6 newly identified loci. Conditional analyses within loci
      showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain
      a secondary independent risk variant. In total, we identified and replicated 28
      independent risk variants for Parkinson's disease across 24 loci. Although the
      effect of each individual locus was small, risk profile analysis showed
      substantial cumulative risk in a comparison of the highest and lowest quintiles
      of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55
      4.30; P = 2 * 10(-16)). We also show six risk loci associated with proximal gene
      expression or DNA methylation. 

PMID- 25064023
TI  - What is the evidence for hardening in the cigarette smoking population? Trends in
      nicotine dependence in the U.S., 2002-2012.
AB  - BACKGROUND: It is unclear whether declines in cigarette smoking in the U.S. have
      resulted in a hardened population of "hardcore" smokers. We studied changes in
      nicotine dependence severity from 2002 to 2012, using data from the National
      Survey on Drug Use and Health. METHODS: We used generalized non-linear factor
      analysis to examine whether individual Nicotine Dependence Syndrome Scale (NDSS)
      items functioned differently over time, and whether average NDSS scores changed
      in a sample of 130,637 current smokers. We also examined trends for individual
      NDSS sub-scales and whether trends were moderated by tobacco consumption and
      socio-demographic factors. RESULTS: Consumption levels and dependence severity
      both declined over the study period. This decline was driven by priority (e.g.,
      avoiding smoke-free locations) and tolerance dimensions of dependence, while
      drive (e.g., craving and smoking to relieve negative affect) and continuity
      (e.g., stability) of smoking did not change. Declines for tolerance were greatest
      among those without serious psychological distress and among middle-aged smokers.
      Drive and continuity increased among women and low income smokers. CONCLUSIONS:
      We did not find evidence of hardening at the population level for smokers in the
      U.S., 2002-2012. However, there is evidence of hardening when considering drive
      and continuity-related nicotine dependence among women and low-income smokers,
      suggesting these sub-groups are experiencing greater severity of craving, smoking
      to relieve negative affect, and regularity of smoking despite reduced
      consumption.

PMID- 25064024
TI  - Potentially modifiable deployment characteristics and new-onset alcohol abuse or
      dependence in the US National Guard.
AB  - BACKGROUND: There is a limited amount of data examining the relation between the
      onset of alcohol abuse/dependence and the experiences of soldiers prior to (pre),
      during (peri) and after (post) military deployment. Some deployment
      characteristics, e.g., military unit cohesion, are potentially modifiable in the
      context of reducing alcohol abuse/dependence peri-/post deployment. We
      investigated the associations between potentially modifiable deployment
      characteristics and peri-/post (incident) alcohol abuse/dependence among deployed
      Ohio Army National Guard (OHARNG) soldiers. METHODS: Using a sample of OHARNG
      (June, 2008 to February, 2009), eligible participants were ever been deployed and
      did not report alcohol abuse/dependence prior to deployment (final sample
      size=963). Interviews assessed soldiers' alcohol abuse/dependence, depression,
      PTSD, deployment related factors (e.g., exposure to warzone stressors) and three
      deployment characteristics (pre-deployment preparedness, unit support during
      deployment, and post-deployment social support). Associations between the three
      deployment characteristics and incident alcohol abuse/dependence (defined as
      abuse or dependence at any point during or after deployment) were estimated using
      logistic regression. RESULTS: Only pre-deployment preparedness was associated
      with incident alcohol abuse/dependence (a non-linear inverted-u shaped relation)
      when controlling for demographics, deployment related factors (e.g., exposure to
      warzone stressors), and the presence of psychopathology that exhibited peri-/post
      deployment. We present these results graphically, plotting incident alcohol
      abuse/dependence over the levels of pre-deployment preparedness. CONCLUSIONS: The
      association between pre-deployment preparedness and alcohol abuse/dependence may
      be characterized as an inverted-U shaped function. Suggestions for how and
      whether to modify pre-deployment preparedness in an effort to reduce peri-/post
      deployment alcohol abuse or dependence should await further research.

PMID- 25064025
TI  - Redefining normal bone and mineral clinical biochemistry reference intervals for
      healthy infants in Canada.
AB  - BACKGROUND: Few normative data exist for routine clinical chemistry in healthy
      term infants, that is, during a time of rapid development. Biochemical markers
      are significantly affected by these physiological changes and the lack of
      appropriate reference intervals may impede diagnostics in infants. OBJECTIVE: To
      define reference intervals for calcium, phosphate, creatinine, and alkaline
      phosphatase in infants from 1 to 12 months of age. DESIGN AND METHODS: This was
      an unblinded secondary analysis of 132 breastfeeding infants participating in a
      vitamin D3 supplementation trial (400-1600IU/d) followed prospectively until 1
      year of age (NCT00381914). Serial non-fasting capillary and spot urine samples
      were collected for the measurement of plasma calcium, phosphate, creatinine, and
      alkaline phosphatase; urinary calcium, phosphate and creatinine (DxC600 Beckman
      Coulter); and whole-blood ionized calcium (ABL 725 Radiometer). All visits were
      conducted at McGill University in Montreal, Canada. RESULTS: All analytes changed
      significantly over time (p<0.05), but there was no effect of sex. From 1 to 12
      months, values decreased for whole-blood ionized calcium; plasma calcium,
      phosphate, and alkaline phosphatase; and urinary calcium:creatinine. Plasma
      creatinine increased. For some analytes, particularly calcium and alkaline
      phosphatase, values were often above the 'typical' adult or older child reference
      limits. Smoothed centile curves (LMS method) were developed to fill existing gaps
      in normative data for these analytes. CONCLUSIONS: Most analytes showed a
      significant change from 1 to 12 months, confirming the need for age-specific
      reference values. These data can assist in the generation of new reference
      intervals for healthy term infants and ultimately improve the care of children.

PMID- 25064026
TI  - NMR-based molecular ruler for determining the depth of intercalants within the
      lipid bilayer. Part IV: studies on ketophospholipids.
AB  - In our companion paper, we described the preparation and intercalation of two
      homologous series of dicarbonyl compounds, methyl n-oxooctadecanoates and the
      corresponding n-oxooctadecanoic acids (n=4-16), into DMPC liposomes. (13)C NMR
      chemical shift of the various carbonyls was analyzed using an E(T)(30) solvent
      polarity-chemical shift correlation table and the corresponding calculated
      penetration depth (in A). An iterative best fit analysis of the data points
      revealed an exponential correlation between E(T)(30) micropolarity and the
      penetration depth (in A) into the liposomal bilayer. However, this study is still
      incomplete, since the plot lacks data points in the important area of moderately
      polarity, i.e., in the E(T)(30) range of 51-45.5 kcal/mol. To correct this
      lacuna, a family of ketophospholipids was prepared in which the above n
      oxooctadecanoic acids were attached to the sn-2 position of a phosphatidylcholine
      with a palmitic acid chain at sn-1. To assist in assignment and detection several
      derivatives were prepared (13)C-enriched in both carbonyls. The various homologs
      were intercalated into DMPC liposomes and give points specifically in the missing
      area of the previous polarity-penetration correlation graph. Interestingly, the
      calculated exponential relationship of the complete graph was essentially the
      same as that calculated in the companion paper based on the methyl n
      oxooctadecanoates and the corresponding n-oxooctadecanoic acids alone. The
      polarity at the midplane of such DMPC systems is ca. 33 kcal/mol and is not
      expected to change very much if we extend the lipid chains. This paper concludes
      with a chemical ruler that maps the changing polarity experienced by an
      intercalant as it penetrates the liposomal bilayer.

PMID- 25064027
TI  - Promoting E2F1-mediated apoptosis in oestrogen receptor-alpha-negative breast
      cancer cells.
AB  - BACKGROUND: Because oestrogen receptor alpha (ERalpha) regulates E2F1 expression
      to mediate tamoxifen resistance in ERalpha-positive breast cancer cells, we aimed
      to define the possible roles of ERalpha and E2F1 in promoting the resistance of
      ERalpha-negative breast cancer cells to 4-hydroxy-tamoxifen (4OHT). METHODS: This
      study utilised conventional techniques to demonstrate the effects of 4OHT on the
      expression of ERalpha and E2F1 and also examined the individual and combined
      effects of 4OHT with dipyridamole (DIPY) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)
      catechin (TMCG) on the oestrogen-negative MDA-MB-231 breast cancer cell line
      using viability assays, Hoechst staining, MALDI-TOF mass spectroscopy, and
      confocal microscopy. RESULTS: Despite the ERalpha-negative status of the MDA-MB
      231 cells, we observed that 4OHT efficiently up-regulated ERalpha in these cells
      and that this upregulation promoted E2F1-mediated cell growth. Because E2F1 plays
      a dual role in cell growth/apoptosis, we designed a therapy incorporating
      TMCG/DIPY to take advantage of the elevated E2F1 expression in these 4OHT-treated
      cells. 4OHT enhances the toxicity of TMCG/DIPY in these ERalpha-negative breast
      cancer cells. CONCLUSIONS: Because TMCG/DIPY treatment modulates the methylation
      status/stability of E2F1, the results demonstrate that therapies targeting the
      epigenetic machinery of cancer cells in the presence of overexpressed E2F1 may
      result in efficient E2F1-mediated cell death.

PMID- 25064028
TI  - A novel mutation in autoimmune regulator gene causes autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy.
AB  - BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      syndrome (APECED) is a rare autosomal recessive disease due to mutations in the
      autoimmune regulator (AIRE) gene, which encodes a transcription factor that
      induces the expression of peripheral tissue-specific antigens in medullary thymic
      epithelial cells. AIM: The purpose of this study was to identify the underlying
      genetic cause in a Chinese family diagnosed with APECED. METHOD: Peripheral blood
      samples were collected from family members. All exons of the AIRE gene and
      adjacent exon-intron sequences were amplified by PCR and subsequently sequenced.
      The functional consequence of the mutations was analyzed by cell transfection and
      in vitro assays. RESULTS: A novel c.483_484insC mutation in exon 4 was
      identified, which resulted in a frame shift predicted to generate a truncated
      protein containing the first 163 AIRE amino acids followed by 52 aberrant amino
      acids. Confocal immunofluorescence microscopy of COS-7 cells transfected with
      wild-type and mutant AIRE constructs showed that wild-type AIRE protein was
      localized mainly in the nucleus, while mutant AIRE was localized mainly in the
      cytoplasm. A luciferase reporter assay showed that the identified mutation
      dramatically inhibited the transactivation activity of AIRE in vitro. CONCLUSION:
      We identified a novel AIRE mutation which alters the intracellular location and
      transcription activity of AIRE, and has implications in the pathogenesis of
      APECED.

PMID- 25064029
TI  - Bone regeneration in a rabbit ulna defect model: use of allogeneic adipose
      derivedstem cells with low immunogenicity.
AB  - Tissue engineering provides new potential treatments for the repair of bone
      defects. Bone-marrow-derived mesenchymal stem cells (BMSCs) represent an
      attractive cell source for therapeutic applications involving tissue engineering,
      although disadvantages, such as pain of harvest and low proliferation efficiency,
      are major limitations to the application of BMSCs in the clinic. Adipose-derived
      stem cells (ASCs) with their multilineage potential and satisfactory
      proliferation potential can be induced into the osteogenic lineage in vitro and
      can be anchored onto suitable scaffolds as seed cells to repair bone defects
      successfully in an autologous setting. Previous studies have indicated that both
      undifferentiated BMSCs and ASCs exhibit immunosuppression and immunoprivilege
      properties. We compare the immuno-function of undifferentiated and osteo
      differentiated ASCs in vitro and explore the feasibility of applying allogeneic
      ASCs to the repair of ulnar bone defects in the rabbit model. Our study
      demonstrates that allogeneic osteogenic differentiated ASCs maintain low
      immunogenicity and negative immunomodulation. The allogeneic osteogenic
      differentiated ASCs combined with demineralized bone matrix successfully
      regenerate ulnar bone defects in rabbits without immunosuppressive therapies. 

PMID- 25064030
TI  - The association between physical characteristics of the ankle joint and the
      mobility performance in elderly people with type 2 diabetes mellitus.
AB  - Previous studies showed that older adults with diabetes have a worse mobility
      performance as compared with those without diabetes. Studies also demonstrated
      that older adults with diabetes have weakened ankle muscle strength, reduced
      joint range in ankle dorsiflexion and worsened ankle joint proprioception as
      compared with control population. The purpose of the present study was to examine
      the relationship between the physical characteristics of the ankle joint and the
      mobility performance in older adults with type 2 diabetes. Older adults with type
      2 diabetes (n=85) were recruited, and Timed Up and Go test (TUG) for mobility
      assessment was performed. Active ankle joint repositioning test was used for
      assessing the ankle joint proprioception sense; peak torque of ankle dorsiflexors
      and plantar flexors were tested by using a Cybex Norm dynamometer, and weight
      bearing lunge test (WBLT) was used for assessing the stiffness of ankle
      dorsiflexion. Our results showed that age, body mass index (BMI), normalized peak
      torque of plantar flexors and dorsiflexors, active ankle joint repositioning test
      errors and the WBLT distance were significantly correlated with the TUG (all
      p<0.001). These ankle characteristics, together with the demographic data of the
      subjects, contributed 59.9% of the variance in the TUG by multiple regression
      analysis. Body mass, ankle plantar flexors strength and ankle joint
      proprioception are important factors contributing to the physical mobility of the
      older adults with type 2 diabetes. 

PMID- 25064031
TI  - Quality of life of older adults in Turkey.
AB  - The purpose of this study was to examine the factors affecting the quality of
      life of the elderly people in Turkey. Three-hundred community-dwelling older
      adults (Mage=68.35, SD=5.80 years) participated in this study. The quality of
      life was examined through World Health Organization Quality of Life Questionnaire
      Older Adults Module Turkish Version (WHOQOL-OLD Turkish). Analysis of Variances
      (ANOVA) showed significant age differences in sensory abilities, social
      participation, and intimacy sub-scale scores. Post hoc Scheffe Test results
      indicated that elderly people aged 75 years and over differed from other age
      groups; although their scores in social participation and intimacy were lower;
      they had higher scores in sensory abilities than those aged 60-65 and 66-74
      years. There were significant differences between the educational levels of these
      elderly people in sensory abilities, autonomy, past-present-and-future
      activities, social participation, and death-and-dying sub-scales. The autonomy,
      past-present-and-future activities, social participation, and death-and-dying
      scores of those with high school education were higher than that of those with
      secondary school or less education except in sensory abilities scores. There were
      differences found between the variable of with whom the elderly people lived and
      of QOL sub-scales of the elderly people's sensory abilities, past-today-and
      future activities, death-and-dying, social participation, and intimacy. In
      addition, the total average score of the QOL sub-scales with the sufficiency of
      income of the elderly people were interconnected. In conclusion, the findings
      revealed that gender, age, education, marital status, childbearing, social
      insurance, health status, living arrangement and income variables are the
      determinant to improving the quality of life of elderly people. 

PMID- 25064032
TI  - Depressive symptoms in older adults are associated with decreased cerebral
      oxygenation of the prefrontal cortex during a trail-making test.
AB  - Growing evidence supports the relationships between depressive symptoms,
      cognitive decline, and brain structural changes in older adults. The purpose of
      this study was to determine whether depressive symptoms are related to cerebral
      oxygenation during cognitive tasks in older adults. In this study, 80 elderly
      subjects (73.9 +/- 5.4 years, 34 males) were evaluated using multi-channel Near
      infrared spectroscopy. Concentration changes (mmolcm/l) in oxy-hemoglobin (oxy
      Hb), as the most reliable available indicator of changes in regional cerebral
      blood flow, in the right and left prefrontal cortex were measured during the
      Trail Making Test Part B (TMT-B). Depressive symptoms were assessed using the
      short Geriatric Depression Scale (GDS). Subjects were divided into a depressive
      group (GDS greater than or equal to 6) and non-depressive group (GDS lower than
      6). In results, Oxy-Hb activation during the TMT-B was significantly smaller in
      the depressive group (n=13) than in the non-depressive group (n=67) in both the
      right and left prefrontal cortex. In the multivariate analysis, GDS scores were
      significantly negatively correlated with oxy-Hb activation after adjusting for
      age, gender and educational history (right, beta=-0.32, p=0.002; left, beta=
      0.25, p=0.02). Less prefrontal activation in older adults with depressive
      symptoms may account for decline in executive function. Further studies are
      needed to investigate the influence of the less brain activation associated with
      depressive symptoms on future cognitive decline and structural brain changes in
      older adults.

PMID- 25064033
TI  - ABO blood group and esophageal carcinoma risk: from a case-control study in
      Chinese population to meta-analysis.
AB  - PURPOSE: The association between ABO blood group and the risk of esophageal
      carcinoma (EC) in previously published studies is uncertain and conflicting. The
      aim of the current study was to determine the correlation of ABO blood group with
      EC risk via a case-control study and meta-analysis. METHODS: We performed a
      population-based case-control study of 3,595 cases and 41,788 controls in Chinese
      population to evaluate the association between ABO blood group and EC risk. Then,
      a comprehensive meta-analysis combining our original data and previously
      published data was conducted to clearly discern the real relationship. The
      strength of association was measured by odds ratios (ORs) with 95% confidence
      intervals (CI). RESULTS: In our case-control study, the risk of EC in blood group
      B was significantly higher than that in non-B groups (A, O, and AB) (OR = 1.15,
      95% CI 1.09-1.21). Compared with non-O groups (A, B, and AB), individuals with
      blood group O demonstrated a reduced risk of EC (OR = 0.90, 95% CI 0.85-0.94).
      The meta-analysis also indicated that blood group B was associated with
      significantly higher EC risk (OR = 1.20, 95% CI 1.10-1.31), and people with blood
      group O had a decreased EC risk (OR = 0.94, 95% CI 0.90-0.99). Neither the case
      control study nor the meta-analysis produced any significant association of blood
      group A or AB with EC risk. CONCLUSION: Results from our case-control study and
      the followed meta-analysis confirmed that there was an increased risk of EC in
      blood group B individuals, whereas a decreased risk of EC was observed in blood
      group O individuals.

PMID- 25064034
TI  - A systematic review on the effect of aspirin in the prevention of post-operative
      arterial thrombosis in patients undergoing total hip and total knee arthroplasty.
AB  - INTRODUCTION: Major surgery is associated with increased risk of venous
      thromboembolism (VTE), which is decreased by anticoagulant drugs. Evidence is
      growing that major surgery is associated with increased risk of arterial
      thrombosis (AT). With the aim of testing aspirin ability in reducing the risk of
      post-operative AT, we performed a systematic review of studies in which
      acetylsalicylic acid (ASA) was compared to anticoagulant drugs in VTE prophylaxis
      of patients undergoing total hip replacement (THR) or total knee replacement
      (TKR). MATERIALS AND METHODS: Studies were identified by reviewing the reference
      of the ACCP guidelines and by electronic search of MEDLINE database from January
      2012 to December 2013 and of the web database www.trialresultscenter.org.
      RESULTS: We analyzed 5 of the 78 studies that were identified by our search
      strategy; they included 5179 patients; the median follow-up was 90 days. The
      incidence of post-operative AT tended to be lower in ASA-treated patients,
      compared to anticoagulant-treated patients, although the difference did not reach
      statistical significance (OR 0.56, 95%CI 0.23-1.35). In contrast, the incidence
      of post-operative VTE tended to be higher in ASA-treated patients, compared to
      anticoagulant-treated patients (1.48, 95% CI 0.93-2.36). CONCLUSIONS: Due to the
      heterogeneity and low quality of the studies, which do not allow firm
      conclusions, it is uncertain whether aspirin is effective in reducing the
      incidence of postoperative AT. Our results do emphasize the need for developing
      specifically designed studies to test the safety and efficacy of ASA in the
      prevention of post-operative AT.

PMID- 25064035
TI  - Prognostic indicators for recurrent thrombotic events in HIV-infected patients
      with acute coronary syndromes: use of registry data from 12 sites in Europe,
      South Africa and the United States.
AB  - AIMS: Limited data are available on prognostic indicators for HIV patients
      presenting with ACS. METHODS AND RESULTS: Data on consecutive patients with HIV
      infection receiving standard highly active antiretroviral therapy (HAART)
      presenting with ACS between January 2001 and September 2012 were collected.
      Cardiac death and myocardial infarction (MI) were the primary end-points. 10,050
      patients with ACS were screened, and among them a total of 201 patients (179
      [89%] males and a median age of 53 [47-62] years) were included, 48% of them
      admitted for ST-elevation myocardial infarction and 14% having left ventricular
      systolic dysfunction (LVSD) at discharge. CD4+ counts less than 200 cells/mm(3)
      were reported in 18 patients (9%), and 136 patients (67%) were treated with
      nucleoside-reverse transcriptase inhibitors (NRTI). After a median of 24 months
      (10-41), 30 patients (15%) died, 12 (6%) for cardiac reasons, 20 (10%) suffered a
      MI, 29 (15%) a subsequent revascularization, and 7 (3%) a stent thrombosis. Other
      than LVSD (hazard ratio=6.4 [95% confidence interval [CI]: 1.6-26: p=0.009]), the
      only other independent predictor of cardiac death was not being treated with NRTI
      (hazard ratio=9.9 [95% CI: 2.1-46: p=0.03); a CD4 cell count <200 cells/mm(3) was
      the only predictor of MI (hazard ratio=5.9 [95% CI: 1.4-25: p=0.016]).
      CONCLUSIONS: HIV patients presenting with ACS are at significantly increased risk
      for cardiac death if not treated with NRTI, and at significantly increased risk
      of MI if their CD4 cell count is <200 cells/mm(3), suggesting that the stage of
      HIV disease (and lack of NRTI treatment) may contribute to cardiovascular
      instability.

PMID- 25064037
TI  - Do latex-based immunoturbidimetric assays conquer a prominent role in von
      Willebrand factor activity detection?

PMID- 25064036
TI  - SAR216471, an alternative to the use of currently available P2Y12 receptor
      inhibitors?
AB  - P2Y12 antagonism is a key therapeutic strategy in the management and prevention
      of arterial thrombosis. The objective of this study was to characterize the
      pharmacodynamic (PD) and pharmacokinetic (PK) properties of SAR216471, a novel
      P2Y12 receptor antagonist. SAR216471 blocks the binding of 2MeSADP to P2Y12
      receptors in vitro (IC50=17 nM). This inhibition was shown to be reversible. It
      potently antagonized ADP-induced platelet aggregation in human and rat platelet
      rich plasma (IC50=108 and 62 nM, respectively). It also inhibited platelet
      aggregation when blood was exposed to collagen or thromboxane A2. Its high
      selectivity was demonstrated against a large panel of receptors, enzymes, and ion
      channels. Despite its moderate bioavailability in rats, oral administration of
      SAR216471 resulted in a fast, potent, and sustained inhibition of platelet
      aggregation where the extent and duration of platelet inhibition were directly
      proportional to its circulating plasma levels. Pre-clinical study of SAR216471 in
      a rat shunt thrombosis model demonstrated a dose-dependent antithrombotic
      activity after oral administration (ED50=6.7 mg/kg). By comparison, ED50 values
      for clopidogrel, prasugrel and ticagrelor were 6.3, 0.35 and 2.6 mg/kg,
      respectively. Finally, the anti-hemostatic effect of SAR216471 and its
      competitors was investigated in a rat tail bleeding model, revealing a favorable
      safety profile of SAR216471. Together, these findings have established a reliable
      antiplatelet profile of SAR216471, and support its potential use in clinical
      practice as an alternative to currently available P2Y12 receptor antagonists.

PMID- 25064038
TI  - Mechanical, hormonal, and hypertrophic adaptations to 10 weeks of eccentric and
      stretch-shortening cycle exercise training in old males.
AB  - The growth promoting effects of eccentric (ECC) contractions are well documented
      but it is unknown if the rate of stretch per se plays a role in such muscular
      responses in healthy aging human skeletal muscle. We tested the hypothesis that
      exercise training of the quadriceps muscle with low rate ECC and high rate ECC
      contractions in the form of stretch-shortening cycles (SSCs) but at equal total
      mechanical work would produce rate-specific adaptations in healthy old males age
      60-70. Both training programs produced similar improvements in maximal voluntary
      isometric (6%) and ECC torque (23%) and stretch-shortening cycle function
      (reduced contraction duration [24%] and enhanced elastic energy storage [12%])
      (p<0.05). The rate of torque development increased 30% only after SSC exercise
      (p<0.05). Resting testosterone and cortisol levels were unchanged but after each
      program the acute exercise-induced cortisol levels were 12-15% lower (p<0.05).
      Both programs increased quadriceps size 2.5% (p<0.05). It is concluded that both
      ECC and SSC exercise training produces favorable adaptations in healthy old
      males' quadriceps muscle. Although the rate of muscle tension during the SSC vs.
      ECC contractions was about 4-fold greater, the total mechanical work seems to
      regulate the hypetrophic, hormonal, and most of the mechanical adaptations.
      However, SSC exercise was uniquely effective in improving a key deficiency of
      aging muscle, i.e., its ability to produce force rapidly. 

PMID- 25064039
TI  - The influence of strength training on muscle activation in elderly persons: a
      systematic review and meta-analysis.
AB  - Age-related muscle weakness is only partially related to muscle atrophy, due to
      neuromuscular changes including reduced voluntary muscle activation and
      antagonist muscle co-activation. The respective contribution of these mechanisms
      in exercise-induced strength gains at higher age is unclear. Here the literature
      was systematically reviewed for studies reporting exercise-induced effects on
      voluntary muscle activation and antagonist muscle co-activation in elderly
      persons. Seventeen relevant studies were identified, 4 investigated voluntary
      muscle activation, 8 antagonist muscle co-activation and 5 studies investigated
      both. Meta-analysis showed an exercise-induced improvement in voluntary
      activation in plantar flexors (weighted mean difference (WMD) +8.8%, p<0.001),
      and knee extensors (WMD +1.8%, p<0.001), with greater gains in activation
      capacity obtained in subjects with lower voluntary activation level prior to the
      onset of training. We found no significant overall effect of strength training on
      antagonist co-activation during ankle plantar flexion (WMD +0.6%, p=0.686) or
      knee extension (WMD -1.1%, p=0.699 for the RCT's and -1.8%, p=0.516 for the non
      controlled trials). Based on our results we can conclude that there is evidence
      for exercise-induced increase in voluntary activation related to strength gains
      in the lower extremities in elderly persons. The results for exercise-induced
      effects on antagonist co-activation are inconsistent and more research is
      necessary to determine its contribution to strength gains following resistance
      training in elderly persons. 

PMID- 25064040
TI  - Feature selection for linear SVMs under uncertain data: robust optimization based
      on difference of convex functions algorithms.
AB  - In this paper, we consider the problem of feature selection for linear SVMs on
      uncertain data that is inherently prevalent in almost all datasets. Using
      principles of Robust Optimization, we propose robust schemes to handle data with
      ellipsoidal model and box model of uncertainty. The difficulty in treating l0
      norm in feature selection problem is overcome by using appropriate approximations
      and Difference of Convex functions (DC) programming and DC Algorithms (DCA). The
      computational results show that the proposed robust optimization approaches are
      superior than a traditional approach in immunizing perturbation of the data. 

PMID- 25064041
TI  - Phototherapy up-regulates dentin matrix proteins expression and synthesis by stem
      cells from human-exfoliated deciduous teeth.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of infrared LED
      (850nm) irradiation on dentin matrix proteins expression and synthesis by
      cultured stem cells from human exfoliated deciduous teeth (SHED). METHODS: Near
      exfoliation primary teeth were extracted (n=3), and SHED cultures were
      characterized by immunofluorescence using STRO-1, CD44, CD146, Nanog and OCT3/4
      antibodies, before experimental protocol. The SHEDs were seeded (3*10(4)
      cells/cm(2)) with DMEM containing 10% FBS. After 24-h incubation, the culture
      medium was replaced by osteogenic differentiation medium, and the cells were
      irradiated with LED light at energy densities (EDs) of 0 (control), 2, or
      4J/cm(2) (n=8). The irradiated SHEDs were then evaluated for alkaline phosphatase
      (ALP) activity, total protein (TP) production, and collagen synthesis (SIRCOLTM
      Assay), as well as ALP, collagen type I (Col I), dentin sialophosphoprotein
      (DSPP), and dentin matrix acidic phosphoprotein (DMP-1) gene expression (qPCR).
      Data were analyzed by Kruskal-Wallis and Mann-Whitney tests (alpha=0.05).
      RESULTS: Increased ALP activity and collagen synthesis, as well as gene
      expression of DSPP and ALP, were observed for both EDs compared with non
      irradiated cells. The ED of 4J/cm(2) also increased gene expression of COL I and
      DMP-1. CONCLUSIONS: In conclusion, infrared LED irradiation was capable of
      biostimulating SHEDs by increasing the expression and synthesis of proteins
      related with mineralized tissue formation, with overall better results for the
      energy dose of 4J/cm(2). CLINICAL SIGNIFICANCE: Phototherapy is an additional
      approach for the clinical application of LED in Restorative Dentistry. Infrared
      LED irradiation of the cavity's floor could biostimulate subjacent pulp cells,
      improving local tissue healing.

PMID- 25064042
TI  - The reliability of Little's Irregularity Index for the upper dental arch using
      three dimensional (3D) digital models.
AB  - AIM: To investigate the inter-examiner variability of contact point displacement
      measurements (used to calculate the overall Little's Irregularity Index (LII)
      score) from digital models of the maxillary arch by four independent examiners.
      METHODS: Maxillary orthodontic pre-treatment study models of ten patients were
      scanned using the Lava(tm) Chairside Oral Scanner (LCOS) and 3D digital models
      were created using Creo((r)) computer aided design (CAD) software. Four
      independent examiners measured the contact point displacements of the anterior
      maxillary teeth using the software. Measurements were recorded randomly on three
      separate occasions by the examiners and the measurements (n=600) obtained were
      analysed using correlation analyses and analyses of variance (ANOVA). RESULTS:
      LII contact point displacement measurements for the maxillary arch were
      reproducible for inter-examiner assessment when using the digital method and were
      highly correlated between examiner pairs for contact point displacement
      measurements >2mm. The digital measurement technique showed poor correlation for
      smaller contact point displacement measurements (<2mm) for repeated measurements.
      The coefficient of variation (CoV) of the digital contact point displacement
      measurements highlighted 348 of the 600 measurements differed by more than 20% of
      the mean compared with 516 of 600 for the same measurements performed using the
      conventional LII measurement technique. CONCLUSIONS: Although the inter-examiner
      variability of LII contact point displacement measurements on the maxillary arch
      was reduced using the digital compared with the conventional LII measurement
      methodology, neither method was considered appropriate for orthodontic research
      purposes particularly when measuring small contact point displacements.

PMID- 25064043
TI  - The value of best-practice guidelines for OSCEs in a postgraduate program in an
      Australian remote area setting.
AB  - INTRODUCTION: Nurses in remote areas of Australia are the primary healthcare
      professionals, who need to be able to deliver comprehensive and culturally
      sensitive care to clients, many of whom are Indigenous Australians. Adequate and
      specific preparation for practice is crucial to the quality of care delivered by
      remote area nurses (RANs). Objective structured clinical examinations (OSCE)
      provide an excellent opportunity for student practice in a simulated environment
      that is safe, authentic, fair and valid when well constructed. Seven integrated
      best practice guidelines (BPGs), previously developed by project team members to
      inform OSCEs within educational programs, provided guidance in restructuring the
      OSCE. This paper provides a detailed analysis of the value of BPGs used in the
      development, teaching and learning, and evaluation of OSCEs in a rural and remote
      postgraduate course for RANs. METHOD: A pre-site visit to the Centre for Remote
      Health, Alice Springs, Northern Territory, was conducted with modification of the
      course and previous OSCE according to BPGs. Following delivery of the course and
      OSCE, evaluations occurred via a mixed method approach. Student surveys (n=15)
      and focus groups (n=13) and staff interviews (n=5) provided an in-depth analysis
      of their perceptions of the revised OSCE. Descriptive statistics were used to
      describe the student sample. The narrative data were transcribed verbatim and
      analysed using content analysis. Triangulation was achieved with the convergence
      of the separate data sources focusing on themes and patterns within and between
      students and tutors. RESULTS: All 15 students and five tutors provided feedback.
      The majority of student participants had limited experience in working in remote
      area nursing prior to participation and therefore the opportunities that availed
      themselves were critical in adequately equipping them with the requisite
      knowledge, skills and abilities. Three themes emerged from the data: (1) value of
      common and significant events in OSCE; (2) power of deliberate actions; and (3)
      learning cultural sensitivity. DISCUSSION: OSCEs in this setting proved to be a
      good way for students to learn the skills required by RANs. Overwhelmingly, the
      modifications using the BPGs were highly valued by students and staff. Three
      themes emerged and were clearly linked to specific BPGs, indicating the positive
      impact the BPGs had on the OSCEs and student learning. The authentic content for
      the scenarios was seen as relevant and motivational for student learning. The
      practice element of the OSCEs enhanced the learning experience and feedback
      supported learning. CONCLUSIONS: OSCEs developed, taught and assessed using BPGs
      were highly valued. The BPGs provided an integrated approach with real-life
      scenarios with a strong cultural perspective - all important features to the
      RANs' future success in providing individualised care to clients in remote areas
      of Australia. Further use of BPGs is recommended.

PMID- 25064044
TI  - Ephrin/Ephrin receptor expression in ammonia-treated rat astrocytes and in human
      cerebral cortex in hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) represents a neuropsychiatric syndrome, which evolves
      as a consequence of a low grade cerebral edema and a concomitant
      oxidative/nitrosative stress response. Ephrin receptors (EphR) and their ligands
      (ephrins) regulate astrocytic glutamate uptake and gliotransmitter release
      thereby governing neurotransmission, but their role in HE and ammonia toxicity is
      unclear. We therefore tested effects of ammonia on expression levels of
      EphR/ephrin isoforms in cultured rat astrocytes and analysed underlying
      mechanisms. NH4Cl induced mRNA expression changes of several EphR/ephrin isoforms
      in a methionine sulfoximine-, NADPH oxidase- and NO synthase-dependent manner in
      cultured astrocytes. A prominent upregulation was noted for EphR A4 mRNA and
      protein in NH4Cl-treated astrocytes. NH4Cl-treatment decreased EphR A4 molecular
      mass to similar extent as found in astrocytes treated with the N-glycosylation
      inhibitor tunicamycin. Knockdown of EphR A4 by siRNA, or treating astrocytes with
      NH4Cl or tunicamycin abolished fibroblast growth factor-induced and EphR A4
      dependent astrocyte proliferation. NH4Cl-treatment also decreased GLAST mRNA
      levels in cultured astrocytes. This effect was sensitive to inhibitors of NAPDH
      oxidase or glutamine synthetase, but was insensitive to siRNA-mediated EphR A4
      knockdown. Eph/ephrin gene expression changes were also found in post mortem
      brain samples of cirrhotic patients without or with HE compared to controls
      suggesting a potential in vivo relevance of the present findings. The present
      study suggests that ammonia modulates EphR/ephrin signaling in astrocytes and in
      the brain of cirrhotic patients with HE with potential implications for deranged
      neurotransmission in HE. 

PMID- 25064046
TI  - Emodin inhibits inducible nitric oxide synthase in a rat model of craniocerebral
      explosive injury.
AB  - To investigate the effects of emodin on blast-induced traumatic brain injury
      (bTBI) in a rat model. Eighty rats were randomly divided into 2 groups (the
      control group and the emodin-treated group; N = 40 per group) and were used to
      establish the model of blast-induced traumatic brain injury. Ten minutes after
      the explosion, an isotonic saline solution (10 mg/kg) or emodin (10 mg/kg) were
      administered via an intraperitoneal injection to the control group and the emodin
      treated group, respectively. At each time point (pre-explosion, 2, 6, 12, 24 h
      after explosion), 2 rats were used for the pathological assessment and 6 rats
      were used for the biochemical assessment. The concentration of nitric oxide (NO)
      and the expression and activity of inducible nitric oxide synthase (iNOS) were
      measured at each time point by spectrophotometry and western blot analysis. Light
      and electron microscopy showed that the brain damage in the emodin-treated group
      was less serious than that observed in the control group. The concentration of NO
      in the emodin-treated group was lower compared with the control group (p < 0.05).
      Western blot analysis showed that protein expression in the emodin-treated group
      was lower than the control group (p < 0.05). Emodin can alleviate brain damage
      after bTBI by inhibiting iNOS. These findings suggest that emodin has a
      protective effect against bTBI. One possible mechanism may occur by inhibiting
      the expression and activity of iNOS and consequently decreasing the concentration
      of NO.

PMID- 25064045
TI  - Genetic dys-regulation of astrocytic glutamate transporter EAAT2 and its
      implications in neurological disorders and manganese toxicity.
AB  - Astrocytic glutamate transporters, the excitatory amino acid transporter (EAAT) 2
      and EAAT1 (glutamate transporter 1 and glutamate aspartate transporter in
      rodents, respectively), are the main transporters for maintaining optimal
      glutamate levels in the synaptic clefts by taking up more than 90% of glutamate
      from extracellular space thus preventing excitotoxic neuronal death. Reduced
      expression and function of these transporters, especially EAAT2, has been
      reported in numerous neurological disorders, including amyotrophic lateral
      sclerosis, Alzheimer's disease, Parkinson's disease, schizophrenia and epilepsy.
      The mechanism of down-regulation of EAAT2 in these diseases has yet to be fully
      established. Genetic as well as transcriptional dys-regulation of these
      transporters by various modes, such as single nucleotide polymorphisms and
      epigenetics, resulting in impairment of their functions, might play an important
      role in the etiology of neurological diseases. Consequently, there has been an
      extensive effort to identify molecular targets for enhancement of EAAT2
      expression as a potential therapeutic approach. Several pharmacological agents
      increase expression of EAAT2 via nuclear factor kappaB and cAMP response element
      binding protein at the transcriptional level. However, the negative regulatory
      mechanisms of EAAT2 have yet to be identified. Recent studies, including those
      from our laboratory, suggest that the transcriptional factor yin yang 1 plays a
      critical role in the repressive effects of various neurotoxins, such as manganese
      (Mn), on EAAT2 expression. In this review, we will focus on transcriptional
      epigenetics and translational regulation of EAAT2.

PMID- 25064047
TI  - Computer-based video to increase HIV testing among emergency department patients
      who decline.
AB  - The Centers for Disease Control and Prevention recommend routine HIV screening in
      clinical settings, including emergency departments (EDs), because earlier
      diagnosis enables treatment before symptoms develop and delivery of interventions
      to reduce continued transmission. However, patients frequently decline testing.
      This study delivered a 16-min video-based intervention to 160 patients who
      declined HIV tests in a high volume, urban ED. One third of participants (n = 53)
      accepted an HIV test post-intervention. Interviews with a subset of participants
      (n = 40) show that before the video, many were unaware HIV testing could be
      conducted without drawing blood, or that results could be delivered in 20 min.

PMID- 25064048
TI  - The neuroanatomic and neurophysiological infrastructure for speech and language.
AB  - New tools and new ideas have changed how we think about the neurobiological
      foundations of speech and language processing. This perspective focuses on two
      areas of progress. First, focusing on spatial organization in the human brain,
      the revised functional anatomy for speech and language is discussed. The
      complexity of the network organization undermines the well-regarded classical
      model and suggests looking for more granular computational primitives, motivated
      both by linguistic theory and neural circuitry. Second, focusing on recent work
      on temporal organization, a potential role of cortical oscillations for speech
      processing is outlined. Such an implementational-level mechanism suggests one way
      to deal with the computational challenge of segmenting natural speech. 

PMID- 25064049
TI  - Natural, but not artificial, facial movements elicit the left visual field bias
      in infant face scanning.
AB  - A left visual field (LVF) bias has been consistently reported in eye movement
      patterns when adults look at face stimuli, which reflects hemispheric
      lateralization of face processing and eye movements. However, the emergence of
      the LVF attentional bias in infancy is less clear. The present study investigated
      the emergence and development of the LVF attentional bias in infants from 3 to 9
      months of age with moving face stimuli. We specifically examined the naturalness
      of facial movements in infants'LVF attentional bias by comparing eye movement
      patterns in naturally and artificially moving faces. Results showed that 3- to 5
      month-olds exhibited the LVF attentional bias only in the lower half of naturally
      moving faces, but not in artificially moving faces. Six- to 9-month-olds showed
      the LVF attentional bias in both the lower and upper face halves only in
      naturally moving, but not in artificially moving faces. These results suggest
      that the LVF attentional bias for face processing may emerge around 3 months of
      age and is driven by natural facial movements. The LVF attentional bias reflects
      the role of natural face experience in real life situations that may drive the
      development of hemispheric lateralization of face processing in infancy.

PMID- 25064050
TI  - Skill acquisition process in vascular anastomosis procedures: a simulation-based
      study.
AB  - OBJECTIVES: There is growing evidence that practice on simulation models can
      improve technical skills in surgery. The aim of this study is to assess the
      effects of our tissue-based simulation model of vascular anastomosis on skill
      acquisition. METHODS: Five junior (Group I) and five senior (Group III)
      cardiovascular surgery residents, and five surgeons from different surgical
      departments (Group II) attended the study. A total of 180 vascular anastomoses on
      a bovine heart simulation model were performed in a 3-month period; each group
      performed 20 anastomoses per month (each participant in each group conducted four
      anastomoses per month). The anastomoses were evaluated according to criteria
      including, duration of the procedure, existence of anastomotic leak, additional
      suture requirements, matching between graft diameter and arteriotomy length,
      patency rates and inadvertent posterior wall injuries. Each practice was recorded
      with a video camera and eventually reviewed by three cardiovascular surgeons, who
      were blinded to groups. Results were compared for analysing the skill acquisition
      process in each group. RESULTS: The mean anastomosis time (Group I: 22.25 +/-
      2.02, 18.10 +/- 0.78, 15.00; Group II: 17.05 +/- 1.39, 15.45 +/- 0.82, 13.00 +/-
      0.79; Group III: 13.65 +/- 0.67, 11.45 +/- 1.14, 10.50 +/- 1.10) and additional
      suture requirements (Group I: 1.95 +/- 0.68, 1.30 +/- 0.80, 1.00 +/- 0.32; Group
      II: 1.80 +/- 0.41, 1.45 +/- 0.60, 1.45 +/- 0.60; Group III: 0.65 +/- 0.48, 0.40
      +/- 0.50, 0.40 +/- 0.50) decreased gradually (P < 0.0001 for each) in all groups.
      There was statistically significant improvement over time in anastomotic leakage
      (Group I: 90, 65, 20%; Group II: 50, 25, 5%; Group III: 20, 25, 5%), match
      between the arteriotomy and the graft (Group I: 35, 25, 75%; Group II: 60, 45,
      85%; Group III: 85, 65, 95%), posterior wall injury (Group I: 70, 50, 15%; Group
      II: 50, 30, 5%; Group III: 30, 30, 5%) and patency (Group I: 45, 15, 75%; Group
      II: 60, 50, 95%; Group III: 80, 85, 95%) in all groups, except for the occurrence
      of anastomotic leaks and patency rates in the senior cardiovascular resident
      group (Group III). CONCLUSIONS: Although the most significant improvement was
      observed in Group I, all groups demonstrated improved skills with the simulation
      model. Therefore, it can be suggested that anastomosis training on tissue-based
      simulation models may be beneficial for the skill acquisition process.

PMID- 25064051
TI  - Surgical left atrial appendage occlusion during cardiac surgery for patients with
      atrial fibrillation: a meta-analysis.
AB  - OBJECTIVES: Concomitant left atrial appendage occlusion (LAAO) during surgical
      ablation has emerged as a potential treatment strategy to reduce stroke and
      perioperative mortality in patients with atrial fibrillation (AF). The present
      meta-analysis aims to assess current evidence on the efficacy and safety between
      LAAO and LAA preservation cohorts for patients undergoing cardiac surgery.
      METHODS: Electronic searches were performed using six electronic databases from
      their inception to November 2013, identifying all relevant comparative randomized
      and observational studies comparing LAAO with non-LAAO in AF patients undergoing
      cardiac surgery. Data were extracted and analysed according to predefined
      endpoints including mortality, stroke, postoperative AF and reoperation for
      bleeding. RESULTS: Seven relevant studies identified for qualitative and
      quantitative analyses, including 3653 patients undergoing LAAO (n = 1716) versus
      non-LAAO (n = 1937). Stroke incidence was significantly reduced in the LAAO
      occlusion group at the 30-day follow-up [0.95 vs 1.9%; odds ratio (OR) 0.46; P =
      0.005] and the latest follow-up (1.4 vs 4.1%; OR 0.48; P = 0.01), compared with
      the non-LAAO group. Incidence of all-cause mortality was significantly decreased
      with LAAO (1.9 vs 5%; OR 0.38; P = 0.0003), while postoperative AF and
      reoperation for bleeding was comparable. CONCLUSIONS: While acknowledging the
      limitations and inadequate statistical power of the available evidence, this
      study suggests LAAO as a promising strategy for stroke reduction perioperatively
      and at the short-term follow-up without a significant increase in complications.
      Larger randomized studies in the future are required, with clearer surgical and
      anticoagulation protocols and adequate long-term follow-up, to validate the
      clinical efficacy of LAAO versus non-LAAO groups.

PMID- 25064052
TI  - Outcomes after different non-sternotomy approaches to left single-vessel
      revascularization: a comparative study with up to 10-year follow-up.
AB  - OBJECTIVES: Various non-sternotomy approaches have been used for left internal
      mammary artery (LIMA) grafting in left single-vessel revascularization. The aim
      of this study was to evaluate the impact of three different non-sternotomy
      techniques on long-term outcomes after left single-vessel revascularization.
      METHODS: A total of 502 patients having single-vessel LAD disease treated from
      April 2003 to May 2013 by minimally invasive direct coronary artery bypass
      grafting (MIDCAB), endoscopically assisted coronary artery bypass grafting
      (EACAB) or robotically assisted direct coronary artery bypass grafting (RADCAB)
      were reviewed. In all cases, distal anastomoses were performed through
      anterolateral minithoracotomy incisions. In-hospital and long-term (10-year)
      outcomes were compared using standard and propensity score-adjusted analyses.
      RESULTS: One hundred and eighty-nine patients had MIDCAB, 76 had EACAB and 236
      had RADCAB. After propensity score matching, RADCAB patients had significantly
      longer operative duration (P < 0.001), whereas MIDCAB and RADCAB patients had
      significantly higher incidence of postoperative angina over the follow-up (P =
      0.034). The groups were comparable regarding in-hospital mortality and
      reintervention rate as well as incidence of myocardial infarction, reoperations,
      reinterventions and cardiac death. All groups showed comparable long-term
      survival (P = 0.943). CONCLUSIONS: MIDCAB, EACAB and RADCAB are associated with
      similar long-term survival and incidence of major adverse cardiac events (MACEs)
      in single-vessel surgical revascularization. However, the endoscopic approach was
      found to be free from the disadvantages of longer operating duration observed in
      RADCAB or higher incidence of angina and shorter freedom from MACEs observed in
      both MIDCAB and RADCAB groups.

PMID- 25064053
TI  - Bacterial nanocellulose as a new patch material for closure of ventricular septal
      defects in a pig model.
AB  - OBJECTIVES: Current materials for closure of cardiac defects such as ventricular
      septal defects (VSDs) are associated with compliance mismatch and a chronic
      inflammatory response. Bacterial nanocellulose (BNC) is a non-degradable
      biomaterial with promising properties such as high mechanical strength,
      favourable elasticity and a negligible inflammatory reaction. The aim of this
      study was the evaluation of a BNC patch for VSD closure and the investigation of
      its in vivo biocompatibility in a chronic pig model. METHODS: Young's modulus and
      tensile strength of BNC patches were determined before and after blood exposure.
      Muscular VSDs were created and closed with a BNC patch on the beating heart in an
      in vivo pig model. Hearts were explanted after 7, 30 or 90 days. Macropathology,
      histology and immunohistochemistry were performed. RESULTS: Young's modulus and
      tensile strength of the BNC patch decreased after blood contact from 6.3 +/- 1.9
      to 3.86 +/- 2.2 MPa (P < 0.01) and 0.33 +/- 0.06 to 0.26 +/- 0.06 MPa (P < 0.01),
      respectively, indicating the development of higher elasticity. Muscular VSDs were
      closed with a BNC patch without residual shunting. After 90 days, a mild chronic
      inflammatory reaction was present. Moreover, there was reduced tissue overgrowth
      in comparison with polyester. Proceeding cellular organization characterized by
      fibromuscular cells, production of extracellular matrix, neoangiogenesis and
      complete neoendothelialization were found. There were no signs of
      thrombogenicity. CONCLUSIONS: BNC patches can close VSDs with good mid-term
      results and its biocompatibility can be considered as satisfactory. Its
      elasticity increases in the presence of blood, which might be advantageous.
      Therefore, it has potential to be used as an alternative patch material in
      congenital heart disease.

PMID- 25064054
TI  - Sulbactam Plays Neuronal Protective Effect Against Brain Ischemia via
      Upregulating GLT1 in Rats.
AB  - The study was undertaken to investigate whether sulbactam protects cerebral
      neurons against ischemia and whether the protection is mediated by regulating the
      expression and uptake activity of glial glutamate transporter-1 (GLT1) in a rat
      global brain ischemia model. The CA1 hippocampus was selected as the observing
      target. Real time quantitative PCR, Western blot and immunohistochemistry assays
      were used to detect GLT1 expression. Neuropathological evaluation was performed
      after thionin staining to determine the extent of the delayed neuronal death
      (DND) of pyramidal neurons. It was found that cerebral ischemia for 8 min induced
      obvious DND of pyramidal neurons and GLT1 downregulation. Sulbactam pretreatment
      significantly upregulated GLT1 expression in sham rats and prevented or reversed
      the GLT1 downregulation normally induced in the ischemic rat brain. Meanwhile,
      sulbactam pretreatment effectively prevented the DND of pyramidal neurons
      normally induced by brain ischemia in a dose-dependent manner. Sulbactam
      posttreatment also protected pyramidal neurons against DND induced by brain
      ischemia although the magnitude of the protective effect was weaker than that in
      sulbactam pretreatment. Furthermore, either antisense knockdown of GLT1
      expression or inhibition of the GLT1 uptake activity with dihydrokainate, a
      selective inhibitor of GLT1, significantly blocked the neuronal protective effect
      of sulbactam. These findings indicate that sulbactam has a neuronal protective
      effect though upregulating GLT1. 

PMID- 25064056
TI  - Origins and impact of the term 'NSAID'.
AB  - This article is an historical investigation of the term non-steroidal anti
      inflammatory drugs and its acronym NSAIDs. Drug names and categories tend to be
      taken at face value in everyday practice, as natural categories existing in their
      own right. The main argument of this article is that the term NSAID is a reminder
      that drug names and categories are complex cultural and social products that have
      been created by specific people, for specific purposes, through specific
      historical processes, and that this is relevant for their use today. The article
      locates the first appearances of the phrase non-steroidal at the entry to the
      1960s, when the iatrogenic tragedies that followed from the introduction of
      corticosteroids had become apparent, and where a clear separation between these
      drugs and emerging anti-inflammatory alternatives was needed. The article then
      shows how both the phrase and the acronym appeared for the first time out of
      specific textual contexts in publications by Michael W. Whitehouse, before they
      were taken up by a wider community and transformed into concepts independent on
      the context of their first appearances. 

PMID- 25064055
TI  - Adenosine A1 receptor-dependent antinociception induced by inosine in mice:
      pharmacological, genetic and biochemical aspects.
AB  - Inosine is an endogenous nucleoside that has anti-inflammatory and
      antinociceptive properties. Inosine is a metabolite of adenosine, and some of its
      actions suggest the involvement of adenosine A1 receptors (A1Rs). The purpose of
      this study was to better understand mechanisms of inosine-induced antinociception
      by investigating the role of A1Rs and purine metabolism inhibitors. Inosine
      antinociception was evaluated using the formalin test in mice. An A1R-selective
      antagonist (DPCPX), A1R knockout mice (gene deletion) and mice with A1R reduced
      expression (antisense oligonucleotides) were used to assess the role of A1Rs in
      the antinociceptive action of inosine. Binding assays were performed to compare
      the affinity of inosine and adenosine for A1Rs. Finally, the role of adenosine
      and inosine breakdown was assessed using deoxycoformycin (DCF) and forodesine
      (FDS) as enzymatic inhibitors of adenosine deaminase and purine nucleoside
      phosphorylase, respectively. Inosine induced antinociception in the formalin test
      when given by systemic, spinal and peripheral routes. Systemically, inosine
      exhibited a potency similar to adenosine, and its effects were inhibited by
      DPCPX. Inosine did not induce antinociception in A1R knockout mice or in mice
      with reduced A1R expression. In binding studies, inosine bound to A1Rs with an
      affinity similar to adenosine. DCF had no effect on inosine actions. FDS
      augmented the antinociceptive effect of a low systemic dose of inosine and, at a
      higher dose, induced antinociception by itself. Collectively, these data indicate
      that inosine is an agonist for A1Rs with antinociceptive properties and a potency
      similar to adenosine and can be considered another endogenous ligand for this
      receptor. 

PMID- 25064057
TI  - Inactive GSK3beta is disturbed in the spinal cord during experimental autoimmune
      encephalomyelitis, but rescued by stem cell therapy.
AB  - Glycogen synthase kinase 3beta (GSK3beta) is known to control neuroinflammation,
      however the status of GSK3beta in multiple sclerosis, the most common
      inflammatory demyelinating disease of the CNS, and its animal model EAE, is
      unknown. In this study, we investigated the expression of phosphorylated
      GSK3beta, the inactive form of GSK3beta, in the spinal cords of EAE mice. We
      demonstrate that while the expression of phosphorylated GSK3beta was present in
      radial astrocytes and neurons of the control mice that received only complete
      Freund's adjuvant, it was absent in radial astrocytes and significantly lower in
      neurons of EAE animals. The loss of phosphorylated GSK3beta in radial glia and
      neurons in EAE spinal cords was concurrent with radial glia migration and
      astrogliosis. This disturbance in the expression of inactive GSK3beta was
      recovered in neurons, but not in the radial glia, after treatment of EAE mice
      with adipose-derived mesenchymal stem cells capable of inducing a Th2 shift.
      Collectively, our results suggest a link between inactive GSK3beta and modulation
      of the immune responses during EAE. Thus, we propose that maintenance of GSK3beta
      in its inactive status may play a role in preserving the normal physiology of the
      spinal cord and amelioration of EAE following stem cell therapy. 

PMID- 25064058
TI  - Is there a relationship between brain-derived neurotrophic factor for driving
      neuronal auditory circuits with onset of auditory function and the changes
      following cochlear injury or during aging?
AB  - Brain-derived neurotrophic factor, BDNF, is one of the most important
      neurotrophic factors acting in the peripheral and central nervous system. In the
      auditory system its function was initially defined by using constitutive knockout
      mouse mutants and shown to be essential for survival of neurons and afferent
      innervation of hair cells in the peripheral auditory system. Further examination
      of BDNF null mutants also revealed a more complex requirement during re
      innervation processes involving the efferent system of the cochlea. Using adult
      mouse mutants defective in BDNF signaling, it could be shown that a tonotopical
      gradient of BDNF expression within cochlear neurons is required for maintenance
      of a specific spatial innervation pattern of outer hair cells and inner hair
      cells. Additionally, BDNF is required for maintenance of voltage-gated potassium
      channels (KV) in cochlear neurons, which may form part of a maturation step
      within the ascending auditory pathway with onset of hearing and might be
      essential for cortical acuity of sound-processing and experience-dependent
      plasticity. A presumptive harmful role of BDNF during acoustic trauma and
      consequences of a loss of cochlear BDNF during aging are discussed in the context
      of a partial reversion of this maturation step. We compare the potentially
      beneficial and harmful roles of BDNF for the mature auditory system with those
      BDNF functions known in other sensory circuits, such as the vestibular, visual,
      olfactory, or somatosensory system. 

PMID- 25064060
TI  - beta2-adrenergic receptors protect axons during energetic stress but do not
      influence basal glio-axonal lactate shuttling in mouse white matter.
AB  - In vitro studies have demonstrated that beta2-adrenergic receptor activation
      stimulates glycogen degradation in astrocytes, generating lactate as a potential
      energy source for neurons. Using in vivo microdialysis in mouse cerebellar white
      matter we demonstrate continuous axonal lactate uptake and glial-axonal metabolic
      coupling of glutamate/lactate exchange. However, this physiological lactate
      production was not influenced by activation (clenbuterol) or blocking (ICI
      118551) of beta2-adrenergic receptors. In two-photon imaging experiments on ex
      vivo mouse corpus callosum subjected to aglycemia, beta2-adrenergic activation
      rescued axons, whereas inhibition of axonal lactate uptake by alpha-cyano-4
      hydroxycinnamic acid (4-CIN) was associated with severe axonal loss. Our results
      suggest that axonal protective effects of glial beta2-adrenergic receptor
      activation are not mediated by enhanced lactate production.

PMID- 25064059
TI  - Localization of excitatory amino acid transporters EAAT1 and EAAT2 in human
      postmortem cortex: a light and electron microscopic study.
AB  - The process of glutamate release, activity, and reuptake involves the astrocyte,
      the presynaptic and postsynaptic neurons. Glutamate is released into the synapse
      and may occupy and activate receptors on both neurons and astrocytes. Glutamate
      is rapidly removed from the synapse by a family of plasma membrane excitatory
      amino acid transporters (EAATs), also localized to neurons and astrocytes. The
      purpose of the present study was to examine EAAT labeling in the postmortem human
      cortex at the light and electron microscopic (EM) levels. The postmortem
      prefrontal cortex was processed for EAAT1 and EAAT2 immunohistochemistry. At the
      light microscopic level, EAAT1 and EAAT2 labeling was found in both gray and
      white matter. Most cellular labeling was in small cells which were
      morphologically similar to glia. In addition, EAAT1-labeled neurons were
      scattered throughout, some of which were pyramidal in shape. At the EM level,
      EAAT1 and EAAT2 labeling was found in astrocytic soma and processes surrounding
      capillaries. EAAT labeling was also found in small astrocytic processes adjacent
      to axon terminals forming asymmetric (glutamatergic) synapses. While EAAT2
      labeling was most prevalent in astrocytic processes, EAAT1 labeling was also
      present in neuronal processes including the soma, axons, and dendritic spines.
      Expression of EAAT1 protein on neurons may be due to the hypoxia associated with
      the postmortem interval, and requires further confirmation. The localization of
      EAATs on the astrocytic plasma membrane and adjacent to excitatory synapses is
      consistent with the function of facilitating glutamate reuptake and limiting
      glutamate spillover. Establishment that EAAT1 and EAAT2 can be measured at the EM
      level in human postmortem tissues will permit testing of hypotheses related to
      these molecules in diseases lacking analogous animal models.

PMID- 25064062
TI  - Differential evolution of signal-responsive RNA elements and upstream factors
      that control alternative splicing.
AB  - Cell signal-regulated alternative splicing occurs for many genes but the
      evolutionary origin of the regulatory components and their relationship remain
      unclear. This review focuses on the alternative splicing components of several
      systems based on the available bioinformatics data. Eight mammalian RNA elements
      for signal-regulated splicing were aligned among corresponding sequences from
      dozens of representative vertebrate species to allow for assessment of the trends
      in evolutionary changes. Four distinct trends were observed. Four of the elements
      are highly conserved in bird, reptile and fish species examined (i); two elements
      can be found in fish but the sequences have been changing till in marsupials or
      higher mammals (ii); one element is almost exclusively found in mammals with
      mostly the same sequence (iii); and one element can be found in birds or lower
      vertebrates but expanded abruptly to have variable numbers of copies in mammals
      (iv). All examined prototype trans-acting factors and protein kinases emerged
      earlier than the RNA elements but additional (paralog) factors emerged in the
      same or later species. Thus, after their emergence mainly in fish or mammals with
      pre-existing prototype trans-acting factors/kinases, half of the elements have
      been highly conserved from fish to humans but the other half have evolved
      differentially with additional trans-acting factors. Their differential evolution
      likely contributes to the exon- and species/class-specific control of alternative
      splicing and its regulation by cell signals. The evolvement of a group of mammal
      specific components would help relay signals from extracellular stimuli to the
      splicing machinery and thus contribute to higher proteomic diversity. 

PMID- 25064063
TI  - Genetic control of anastomosis in Podospora anserina.
AB  - We developed a new microscopy procedure to study anastomoses in the model
      ascomycete Podospora anserina and compared it with the previous method involving
      the formation of balanced heterokaryons. Both methods showed a good correlation.
      Heterokaryon formation was less quantifiable, but enabled to observe very rare
      events. Microscopic analysis evidenced that anastomoses were greatly influence by
      growth conditions and were severely impaired in the IDC mutants of the PaMpk1,
      PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons,
      albeit with a delay when compared to the wild type. We also identified IDC(821),
      a new mutant presenting a phenotype similar to the other IDC mutants, including
      lack of anastomosis. Complete genome sequencing revealed that IDC(821) was
      affected in the orthologue of the Neurospora crassa So gene known to control
      anastomosis in several other ascomycetes. 

PMID- 25064064
TI  - Similar is not the same: differences in the function of the (hemi-)cellulolytic
      regulator XlnR (Xlr1/Xyr1) in filamentous fungi.
AB  - The transcriptional activator XlnR (Xlr1/Xyr1) is a major regulator in fungal
      xylan and cellulose degradation as well as in the utilization of d-xylose via the
      pentose catabolic pathway. XlnR homologs are commonly found in filamentous
      ascomycetes and often assumed to have the same function in different fungi.
      However, a comparison of the saprobe Aspergillus niger and the plant pathogen
      Magnaporthe oryzae showed different phenotypes for deletion strains of XlnR. In
      this study wild type and xlnR/xlr1/xyr1 mutants of five fungi were compared:
      Fusarium graminearum, M. oryzae, Trichoderma reesei, A. niger and Aspergillus
      nidulans. Growth profiling on relevant substrates and a detailed analysis of the
      secretome as well as extracellular enzyme activities demonstrated a common role
      of this regulator in activating genes encoding the main xylanolytic enzymes.
      However, large differences were found in the set of genes that is controlled by
      XlnR in the different species, resulting in the production of different
      extracellular enzyme spectra by these fungi. This comparison emphasizes the
      functional diversity of a fine-tuned (hemi-)cellulolytic regulatory system in
      filamentous fungi, which might be related to the adaptation of fungi to their
      specific biotopes. Data are available via ProteomeXchange with identifier
      PXD001190. 

PMID- 25064061
TI  - Molecular mechanisms of dopaminergic subset specification: fundamental aspects
      and clinical perspectives.
AB  - Dopaminergic (DA) neurons in the ventral mesodiencephalon control locomotion and
      emotion and are affected in psychiatric and neurodegenerative diseases, such as
      Parkinson's disease (PD). A clinical hallmark of PD is the specific degeneration
      of DA neurons located within the substantia nigra (SNc), whereas neurons in the
      ventral tegmental area remain unaffected. Recent advances have highlighted that
      the selective vulnerability of the SNc may originate in subset-specific molecular
      programming during DA neuron development, and significantly increased our
      understanding of the molecular code that drives specific SNc development. We here
      present an up-to-date overview of molecular mechanisms that direct DA subset
      specification, integrating our current knowledge about subset-specific roles of
      transcription factors, signaling pathways and morphogenes. We discuss strategies
      to further unravel subset-specific gene-regulatory networks, and the clinical
      promise of fundamental knowledge about subset specification of DA neurons, with
      regards to cell replacement therapy and cell-type-specific vulnerability in PD.

PMID- 25064065
TI  - History, complexity and health systems research.

PMID- 25064066
TI  - Rejoinder to Lund: plan and action in mental health research and policy in low
      and middle-income countries.

PMID- 25064067
TI  - The role of civil society in health care reforms: an arena for hegemonic
      struggles.
AB  - The present paper argues that current mainstream understandings of civil society
      as ontologically different from the state and essentially positive (either
      normative or functionally) are problematic in order to understand the development
      of health care reforms. The paper proposes to ground an explanation of the role
      of civil society in health care reforms in a Gramscian understanding of civil
      society as analytically different from the state, and as an arena for hegemonic
      struggles. The study of health care reform in Israel serves as a case study for
      this claim.

PMID- 25064068
TI  - Sliding self-locking first stitch and Aberdeen knot in suture reinforcement with
      omentoplasty of the laparoscopic gastric sleeve staple line.

PMID- 25064069
TI  - Ex vivo endothelin dependent contraction of the remodeled rat spiral artery.
AB  - INTRODUCTION: Similarities of the rat to the human placenta make rat pregnancy
      models relevant to the study of human gestational diseases. Understanding of
      species differences is necessary to extrapolate from animal models to humans. We
      observed alpha-smooth muscle actin (alphaSMA) expression in rat endovascular
      trophoblasts (EVasT) and investigated the spatial and temporal expression of
      smooth muscle (SM) proteins and their potential function in remodeled spiral
      artery. METHODS: Rat placentas were examined from gestational day 13 to term, and
      were immunostained for cytokeratin, alphaSMA, alpha heavy chain of SM myosin, non
      muscle myosin, Rho proteins, regulators of SM gene expression, myocardin, an
      early marker of SM differentiation and endothelin receptors A and B (ETA, ETB).
      Transmission electron microscopy (TEM) was performed. Modified spiral artery
      rings were studied ex vivo for endothelin-1- induced contraction. RESULTS: EVasT
      expressed SM proteins co-localizing with cytokeratin confirming their
      trophoblastic origin from gestational day 13 to term. Thin fibers, consistent
      with actin fibers, were observed by TEM, in the cellular localization of alphaSMA
      in EVasT. Functional experiments revealed that addition of 10(-7) M endothelin-1
      ex vivo reduced vascular lumen area by 11.1% +/- 1.8% compared with control. This
      effect was reduced to only 1.0 +/- 1.7% with ETA antagonist, and to 5.4 +/- 1.7%
      contraction by ETB antagonist, p < 0.002, for all. DISCUSSION: The expression of
      SM proteins in EVasT along with the contractibility of the rat remodeled spiral
      artery ex vivo, suggest that some vascular tone is potentially maintained by
      endothelin-1, and may play a role in situations of dysregulation of the
      vasoactive systems.

PMID- 25064070
TI  - Placental miR-1301 is dysregulated in early-onset preeclampsia and inversely
      correlated with maternal circulating leptin.
AB  - INTRODUCTION: miRNAs are small non-coding RNAs important for the regulation of
      mRNA in many organs including placenta. Adipokines and specifically leptin are
      known to be dysregulated in preeclampsia, but little is known regarding their
      regulation by miRNAs during pregnancy. METHODS: We performed high-throughput
      sequencing of small RNAs in placenta from 72 well-defined patients: 23 early
      onset preeclampsia (PE), 26 late-onset PE and 23 controls. The regulation of some
      miRNAs was confirmed on qRT-PCR. Maternal circulating levels and placental mRNA
      of leptin, resistin and adiponectin were measured using Bio-Plex and qRT-PCR.
      RESULTS: We found that miR-1301, miR-223 and miR-224 expression was downregulated
      in early-onset PE, but not in late-onset PE, compared to controls. In silico
      analysis predicted the leptin gene (LEP) to be a target for all three miRNAs.
      Indeed, we found significant correlation between maternal circulating levels of
      leptin and placental LEP expression. In addition, we found a significant inverse
      correlation between maternal circulating leptin/placental LEP expression and
      placental miR-1301 expression levels. Interestingly, placental expression of miR
      1301 was also correlated with newborn weight percentile and inversely correlated
      with both maternal systolic and diastolic blood pressure prior to delivery.
      DISCUSSION: Our results confirm that placenta is a major site of LEP expression
      during pregnancy. It further suggests that miR-1301 could be involved in the
      regulation of leptin during pregnancy and may play a role in early-onset PE.
      CONCLUSIONS: miR-1301 is dysregulated in early-onset preeclampsia and could
      possibly play a role in the regulation of leptin during pregnancy.

PMID- 25064071
TI  - Macrosomia has its roots in early placental development.
AB  - INTRODUCTION: We sought to determine if early placental size, as measured by 3
      dimensional ultrasonography, is associated with an increased risk of delivering a
      macrosomic or large-for-gestational age (LGA) infant. METHODS: We prospectively
      collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11-14
      weeks and 18-24 weeks. Birth weights were collected from the medical records.
      After delivery, the ultrasound volume set were used to measure the placental
      volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean
      placental and chorionic diameters (MPD and MCD, respectively). Placental measures
      were analyzed as predictors of macrosomia (birth weight >=4000 g) and LGA (birth
      weight >=90th percentile). RESULTS: The 578 pregnancies with first trimester
      volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects
      also had second trimester volumes available. A higher PV and PQ were both
      significantly associated with macrosomia and LGA in both the first and second
      trimesters. Second trimester MPD was significantly associated with both outcomes
      as well, while second trimester MCD was only associated with LGA. The above
      associations remained significant after adjusting for maternal demographic
      variables such as race, ethnicity, age and diabetes. Adjusted models yielded
      moderate prediction of macrosomia and LGA (AUC: 0.71-0.77). CONCLUSIONS:
      Sonographic measurement of the early placenta can identify pregnancies at greater
      risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by
      early placental growth and development.

PMID- 25064072
TI  - The SKIV2L RNA exosome limits activation of the RIG-I-like receptors.
AB  - Sensors of the innate immune system that detect intracellular nucleic acids must
      be regulated to prevent inappropriate activation by endogenous DNA and RNA. The
      exonuclease Trex1 regulates the DNA-sensing pathway by metabolizing potential DNA
      ligands that trigger it. However, an analogous mechanism for regulating the RIG-I
      like receptors (RLRs) that detect RNA remains unknown. We found here that the
      SKIV2L RNA exosome potently limited the activation of RLRs. The unfolded protein
      response (UPR), which generated endogenous RLR ligands through the cleavage of
      cellular RNA by the endonuclease IRE-1, triggered the production of type I
      interferons in cells depleted of SKIV2L. Humans with deficiency in SKIV2L had a
      type I interferon signature in their peripheral blood. Our findings reveal a
      mechanism for the intracellular metabolism of immunostimulatory RNA, with
      implications for specific autoimmune disorders. 

PMID- 25064074
TI  - Receptor like proteins associate with SOBIR1-type of adaptors to form bimolecular
      receptor kinases.
AB  - Receptor like proteins (RLPs) build large protein families in all higher plants.
      Apart from RLPs with conserved roles in development, an increasing number of RLPs
      could be associated with functions as immunoreceptors detecting specific patterns
      from a variety of pathogens. Recent work showed that functionality of these RLPs,
      at least those with leucine rich repeats in their extracellular domain, depends
      on association with the common adaptor kinase SOBIR1. We propose that these
      RLP/adaptor complexes, formed in the absence of ligands, are bimolecular
      equivalents of genuine receptor kinases. Similar to receptor kinases, activation
      of these RLP/adaptor complexes seems to require a ligand-dependent interaction
      step with co-receptors like BAK1 or other SERKs. 

PMID- 25064073
TI  - The cytokine TGF-beta co-opts signaling via STAT3-STAT4 to promote the
      differentiation of human TFH cells.
AB  - Understanding the developmental mechanisms of follicular helper T cells (TFH
      cells) in humans is relevant to the clinic. However, the factors that drive the
      differentiation of human CD4+ helper T cells into TFH cells remain largely
      undefined. Here we found that transforming growth factor-beta (TGF-beta) provided
      critical additional signals for the transcription factors STAT3 and STAT4 to
      promote initial TFH differentiation in humans. This mechanism did not appear to
      be shared by mouse helper T cells. Developing human TFH cells that expressed the
      transcriptional repressor Bcl-6 also expressed RORgammat, a transcription factor
      typically expressed by the TH17 subset of helper T cells. Our study documents a
      mechanism by which TFH cells and TH17 cells emerge together in inflammatory
      environments in humans, as is often observed in many human autoimmune diseases.

PMID- 25064075
TI  - Jasmonate signaling and crosstalk with gibberellin and ethylene.
AB  - The phytohormone jasmonate (JA) plays essential roles in plant growth,
      development and defense. In response to the JA signal, the CORONATINE INSENSITIVE
      1 (COI1)-based SCF complexes recruit JASMONATE ZIM-domain (JAZ) repressors for
      ubiquitination and degradation, and subsequently regulate their downstream
      signaling components essential for various JA responses. Tremendous progress has
      been made in understanding the JA signaling pathway and its crosstalk with other
      phytohormone pathways during the past two decades. Recent studies have revealed
      that a variety of positive and negative regulators act as targets of JAZs to
      control distinctive JA responses, and that JAZs and these regulators function as
      crucial interfaces to mediate synergy and antagonism between JA and other
      phytohormones. Owing to different regulatory players in JA perception and JA
      signaling, a fine-tuning of JA-dependent processes in plant growth, development
      and defense is achieved. In this review, we will summarize the latest progresses
      in JA signaling and its crosstalk with gibberellin and ethylene. 

PMID- 25064076
TI  - Chromatographic fingerprint analysis of the floral parts of Trollius chinensis.
AB  - This study provided a practical procedure, for the first time, to compare the
      component difference of the floral parts of Trollius chinensis and identify the
      characteristic peaks of each floral part using the high-performance liquid
      chromatographic fingerprint technique followed by similarity analysis. The
      results showed that the constituents of different floral parts exhibited lower
      similarity than those of the same part. It can be concluded that the procedure
      established herein is useful for analysis of variability in constituent
      distribution of herbal drugs, and the components are unevenly distributed in the
      floral parts of T. chinensis. 

PMID- 25064077
TI  - Bilateral anterior sternothoracotomy (clamshell incision): a suitable alternative
      for bilateral lung sarcoma metastasis in children.
AB  - BACKGROUND: The aim of our study was to assess the postoperative course of
      bilateral anterior sternothoracotomy (BAT) in children with sarcoma metastases,
      in a curative care perspective. METHODS: We reviewed the records of seven
      patients younger than 18 years old, who underwent surgical procedures for sarcoma
      metastasis to the lung between 2000 and 2012. We compared the postoperative
      course of the BAT group with that of patients who underwent unilateral
      posterolateral thoracotomies (PLTs) for the same etiology. RESULTS: Of 17
      surgical procedures, there were seven BAT and 10 unilateral PLT. Mean ages at the
      time of the procedures were 12.9 +/- 5.4 years old for BAT, and 17.4 +/- 1.9
      years old for PLT. Mean operative time was 173 +/- 37 minutes in the BAT group,
      and 145 +/- 39 minutes in the PLT group (P = 0.19). Patients received epidural
      analgesia in all cases; this was for a mean time of 3.8 +/- 1.3 days in the BAT
      group, and 3.21 +/- 4 days in the PLT group (P = 0.36). Chest tubes were removed
      after 3.6 +/- 1.3 days in the BAT group, and 3 +/- 1.2 days in the PLT group (P =
      0.69). Total hospital stay was 7.7 +/- 6.6 days in the BAT group, and 7 +/- 1.2
      days in the PLT group (P = 0.72). CONCLUSION: In our experience, BAT seems
      suitable and shows outcomes similar to those of PLT for sarcoma metastasis
      resection. The BAT procedure allows the manual exploration of both lungs during a
      single surgical intervention, and so reduces the delay of further therapies.

PMID- 25064078
TI  - Theoretical modelling of fibrinogen supplementation with therapeutic plasma,
      cryoprecipitate, or fibrinogen concentrate.
AB  - BACKGROUND: We aimed to create a theoretical tool to model the effect of three
      haemostatic agents containing fibrinogen (therapeutic plasma, cryoprecipitate,
      and fibrinogen concentrate) on the patient's plasma fibrinogen level. METHODS: A
      mathematical model was developed step-wise. The relationship between the amount
      of haemostatic agent and plasma fibrinogen level was plotted for each agent. A
      fibrinogen concentration simulator (FCS(amount)) was developed, where the amount
      of haemostatic agent was calculated from patient characteristics, agent
      characteristics, and target plasma fibrinogen level. Refinements were introduced
      so that (i) FCS(amount) would account for in vivo fibrinogen recovery, (ii)
      circulatory volume would not increase ad infinitum with increasing amounts, and
      (iii) red blood cells would be included in the simulation if haematocrit
      decreased below a certain level. A second FCS (FCS(level)) was created to
      calculate fibrinogen levels resulting from specified amounts of haemostatic
      agents. RESULTS: Fibrinogen concentration in haemostatic agents has a critical
      impact on their ability to increase patients' fibrinogen levels. If the target
      plasma fibrinogen level approaches the concentration of the fibrinogen source,
      the required amounts increase exponentially; it is impossible to achieve a target
      above the concentration of the fibrinogen source. CONCLUSIONS: We successfully
      developed two theoretical tools answering the questions: 'How much therapeutic
      plasma, cryoprecipitate, or fibrinogen concentrate would be needed to achieve a
      specified target fibrinogen level?' and 'What would be the resultant fibrinogen
      level for a specified amount of haemostatic agent?' The current tools are not
      intended for clinical application, but they are potentially useful for
      educational purposes.

PMID- 25064079
TI  - Neuroprotective effect of the chemical chaperone, trehalose in a chronic MPTP
      induced Parkinson's disease mouse model.
AB  - Parkinson's disease (PD) is a progressive motor disease of unknown etiology in
      the majority of cases. The clinical features of PD emerge due to selective
      degeneration of dopamine (DA) neurons in the substantia nigra pars compacta
      (SNc), which project to the caudate putamen (CPu) where they release DA. In the
      current in vivo mouse model study, we tested trehalose for its ability to protect
      against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage to DA
      neurons. Trehalose is a naturally occurring disaccharide present in plants and
      animals and appears capable of protecting cells against various environmental
      stresses. The effect of trehalose is likely due to its action as a
      pharmacological chaperone which promotes protein stability. In the present study,
      there were four treatment groups: saline only (control); probenecid only;
      MPTP+probenecid; and trehalose+MPTP+probenecid. MPTP-induced losses in tyrosine
      hydroxylase and DA transporter immunoreactivity in the ventral midbrain SNc and
      CPu were significantly reduced by trehalose. Decreases in CPu dopamine levels
      produced by MPTP were also blocked by trehalose. Microglial activation and
      astrocytic hypertrophy induced by MPTP were greatly reduced by trehalose,
      indicating protection against neuroinflammation. These effects are commensurate
      with the observed trehalose sparing of motor deficits produced by MPTP in this
      mouse model. Two tight junctional proteins, ZO-1 and occludin, are downregulated
      following MPTP treatment and trehalose blocks this effect. Likewise, the glucose
      transporter-1 that is expressed in brain endothelial cells is also protected by
      trehalose from MPTP-induced down-regulation. This study is the first to
      demonstrate using fluoro-turoquoise FT gel perfusion techniques, the protection
      afforded by trehalose from MPTP-induced damage to microvessels and endothelial
      and suggests that trehalose therapy may have the potential to slow or ameliorate
      PD pathology. 

PMID- 25064080
TI  - Galantamine prevents long-lasting suppression of excitatory synaptic transmission
      in CA1 pyramidal neurons of soman-challenged guinea pigs.
AB  - Galantamine, a drug currently approved for the treatment of Alzheimer's disease,
      has recently emerged as an effective pretreatment against the acute toxicity and
      delayed cognitive deficits induced by organophosphorus (OP) nerve agents,
      including soman. Since cognitive deficits can result from impaired glutamatergic
      transmission in the hippocampus, the present study was designed to test the
      hypothesis that hippocampal glutamatergic transmission declines following an
      acute exposure to soman and that this effect can be prevented by galantamine. To
      test this hypothesis, spontaneous excitatory postsynaptic currents (EPSCs) were
      recorded from CA1 pyramidal neurons in hippocampal slices obtained at 1h, 24h, or
      6-9 days after guinea pigs were injected with: (i) 1*LD50 soman (26.3MUg/kg,
      s.c.); (ii) galantamine (8mg/kg, i.m.) followed 30min later by 1*LD50 soman,
      (iii) galantamine (8mg/kg, i.m.), or (iv) saline (0.5ml/kg, i.m.). In soman
      injected guinea pigs that were not pretreated with galantamine, the frequency of
      EPSCs was significantly lower than that recorded from saline-injected animals.
      There was no correlation between the severity of soman-induced acute toxicity and
      the magnitude of soman-induced reduction of EPSC frequency. Pretreatment with
      galantamine prevented the reduction of EPSC frequency observed at 6-9 days after
      the soman challenge. Prevention of soman-induced long-lasting reduction of
      hippocampal glutamatergic synaptic transmission may be an important determinant
      of the ability of galantamine to counter cognitive deficits that develop long
      after an acute exposure to the nerve agent. 

PMID- 25064081
TI  - The experience of dysmenorrhoea among Ghanaian senior high and university
      students: pain characteristics and effects.
AB  - BACKGROUND: Dysmenorrhoea is a common problem of women at the reproductive age
      and may have negative effect on the education of females at various stages on the
      educational ladder. CONTEXT AND PURPOSE: This study sought to gain an in-depth
      understanding of the experience of dysmenorrhoea and its effect on female
      students in a secondary and a tertiary institution in Accra, Ghana. METHODS: The
      study employed a descriptive phenomenology design and was conducted at a
      University and a Senior High School (SHS) in Accra. Purposive and snowball
      sampling techniques were used to recruit participants and data was saturated with
      16 participants. Concurrent analysis was done by applying the processes of
      content analysis and the NVivo software was used to manage the data. RESULTS: It
      was realized that dysmenorrhoea is associated with symptoms such as diarrhoea,
      headache and vomiting. Pain may start one week to the day of menstruation and the
      severity differed across the days of menstruation. The effect of dysmenorrhoea
      included activity intolerance, altered emotion and interaction, altered sleep
      pattern, absenteeism and inattentiveness, wishes and regrets, and misconceptions.
      CONCLUSIONS: It was concluded that severe dysmenorrhoea has a debilitating effect
      on female students and is associated with misconceptions that could result in
      drastic action with fatal consequences. Thus, there is the need to enhance
      education on dysmenorrhoea, and an aggressive step should be taken to effectively
      manage dysmenorrhoea.

PMID- 25064082
TI  - Cold hardiness and biochemical response to low temperature of the unfed bush tick
      Haemaphysalis longicornis (Acari: Ixodidae).
AB  - BACKGROUND: The survival of overwintering ticks, is critical for their subsequent
      population dynamics in the spring, and consequent transmission of tick-borne
      diseases. Survival is largely influenced by the severity of the winter
      temperatures and their degree of cold hardiness at the overwintering stage. The
      bush tick Haemaphysalis longicornis, is widely distributed in China, and can
      transmit various pathogens that pose serious medical/veterinary problems. In the
      present study we investigated the effect of low temperature stress to tick
      survival, super-cooling point and body content of water, glycerol and total
      protein. METHODS: After various temperature acclimations, the super-cooling point
      was measured by Ni/CrNi-thermocouples with a precision temperature recorder.
      Water content was determined from weight loss of the sample exposed to 60 degrees
      C for 48 h. Glycerol content was determined using Free Glycerol Reagent as
      directed by the manufacturer, and total protein was determined using the Bradford
      assay. RESULTS: The 50% mortality temperatures for the adults and nymphs were 
      13.7 degrees C and -15.2 degrees C, respectively; and the discriminating
      temperatures for the adults and nymphs were -16.0 degrees C and -17.0 degrees C,
      respectively. The super-cooling points of the adults and nymphs were -19.0
      degrees C and -22.7 degrees C, respectively. The water content of adult H.
      longicornis decreased substantially after acclimation at 0 degrees C for 10 d,
      whereas the nymphs decreased after acclimation at 0 degrees C for 20 d, and the
      glycerol and proteins of both nymphs and adults were significantly increased (p <
      0.01) when stressed at 0 degrees C for 10 d. CONCLUSIONS: In H. longicornis, low
      temperature stress can enhance its cold hardiness and trigger appropriate
      responses, including reducing water content, and increasing glycerol and total
      protein content.

PMID- 25064083
TI  - Extracapsular en bloc resection in pituitary adenoma surgery.
AB  - PURPOSE: A pituitary pseudocapsule often contains tumor tissue and should be
      removed for radical resection. It can be used as a surgical plane for more
      radical resection of the tumor in many cases of pituitary adenomas. We evaluated
      the advantages and disadvantages of extracapsular en bloc capsulectomy. METHODS:
      From 1992 until 2011, 1,089 treated patients were grouped according to the
      resection technique: en bloc capsulectomy, fragmented capsulectomy, or piecemeal
      resection. Their surgical and endocrinological outcomes and complications were
      evaluated. RESULTS: Extracapsular tumor resection was performed in 263 patients;
      en bloc capsulectomy in 94 patients and fragmented capsulectomy in 169, whereas
      piecemeal resection was performed in 826. Extracapsular resection was performed
      more frequently in prolactin- and thyroid-stimulating hormone-secreting tumors.
      Total resection was more frequently achieved in extracapsular resection and its
      chance was 100% when tumors were removed in an en bloc fashion. For the
      functioning pituitary adenomas, endocrinological remission was achieved in all
      patients whose tumors were removed in an en bloc fashion and there was no
      recurrence. Postoperative cerebrospinal fluid (CSF) rhinorrhea developed in 4.2
      and 2.7% in the extracapsular resection group and the piecemeal resection groups,
      respectively. The chance of postoperative aggravation of pituitary function was
      not statistically different between groups. CONCLUSIONS: Extracapsular resection
      is critical for radical tumor resection and endocrinological remission. The
      removal of a pseudocapsule does not increase the risk of postoperative
      hypopituitarism nor postoperative CSF rhinorrhea.

PMID- 25064084
TI  - A cautionary note on generic depot octreotide.

PMID- 25064085
TI  - Analysis of breast thermograms using Gabor wavelet anisotropy index.
AB  - In this study, an attempt is made to distinguish the normal and abnormal tissues
      in breast thermal images using Gabor wavelet transform. Thermograms having
      normal, benign and malignant tissues are considered in this study and are
      obtained from public online database. Segmentation of breast tissues is performed
      by multiplying raw image and ground truth mask. Left and right breast regions are
      separated after removing the non-breast regions from the segmented image. Based
      on the pathological conditions, the separated breast regions are grouped as
      normal and abnormal tissues. Gabor features such as energy and amplitude in
      different scales and orientations are extracted. Anisotropy and orientation
      measures are calculated from the extracted features and analyzed. A distinctive
      variation is observed among different orientations of the extracted features. It
      is found that the anisotropy measure is capable of differentiating the structural
      changes due to varied metabolic conditions. Further, the Gabor features also
      showed relative variations among different pathological conditions. It appears
      that these features can be used efficiently to identify normal and abnormal
      tissues and hence, improve the relevance of breast thermography in early
      detection of breast cancer and content based image retrieval. 

PMID- 25064086
TI  - Irreversible electroporation of unresectable soft tissue tumors with vascular
      invasion: effective palliation.
AB  - BACKGROUND: Irreversible electroporation (IRE) has recently been added as an
      additional therapeutic ablative option in patients with locally advanced cancers
      (LAC) involving vital structures. IRE delivers localized electric current by peri
      tumoral discrete probes to attain irreversible changes in cell membrane leading
      to cell death. The aim of this study was to evaluate the long-term effects of IRE
      in the treatment of locally advanced tumors. METHODS: A prospective IRB approved
      evaluation of 107 consecutive patients from 7 institutions with tumors that had
      vascular invasion treated with IRE from 5/2010 to 1/2012. LAC was defined as
      primary tumor with <5 mm from major vascular structure based on pre-operative
      dynamic imaging or intra-operative criteria. RESULTS: IRE as utilized in LAC in
      the liver (N = 42, 40%) and pancreas (N = 37, 35%), with a median number of
      lesions being 2 with a mean target size of 3 cm. IRE attributable morbidity rate
      was 13.3% (total 29.3%) with high-grade complications seen in 4.19% (total
      12.6%). No significant vascular complications were seen, and of the high-grade
      complications, bleeding (2), biliary complications (3) and DVT/PE (3) were the
      most common. Complications were more likely with pancreatic lesions (p = 0.0001)
      and open surgery (p = 0.001). Calculated local recurrence free survival (LRFS)
      was 12.7 months with a median follow up of 26 months censured at last follow up.
      The tumor target size was inversely associated with recurrence free survival (b =
      0.81, 95% CI: 1.6 to 4.7, p value = 0.02) but this did not have a significant
      overall survival impact. CONCLUSIONS: IRE represents a novel therapeutic option
      in patients with LAC involving vital structures that are not amenable to surgical
      resection. Acceptable to high local disease control and the long LRFS can be
      achieved with this therapy in combination with other multi-disciplinary
      therapies.

PMID- 25064087
TI  - Rapid-response parenting intervention in diagnostic centers as a patient-centered
      innovation for autism spectrum disorders.
AB  - Parents of children newly diagnosed with autism spectrum disorders are a high
      need population for whom skills-based parenting interventions likely help.
      Diagnostic centers are compelling locations to deliver parenting interventions
      because families are served in an accessible location and at a time they receive
      overwhelming treatment recommendations. Additionally, behavioral interventions in
      these settings may be especially effective in helping parents feel an early sense
      of mastery of disruptive child behaviors and enable families grappling with this
      diagnosis to be proactive and build resilience. Providing parenting interventions
      in diagnostic centers is a promising service delivery innovation and deserves
      expanded piloting and testing. 

PMID- 25064088
TI  - Is personal recovery in schizophrenia predicted by low cognitive insight?
AB  - Recovery is a widely discussed concept in the field of research, treatment, and
      public policy regarding serious mental illness, and mainly schizophrenia. Aim of
      our study was to assess the relationship between personal recovery and prediction
      variables, as psychopathology, neurocognition, clinical and cognitive insight,
      and social functioning in inpatients affected by schizophrenia, with a special
      interest on cognitive insight. We assessed 76 inpatients affected by
      schizophrenia at their hospital discharge. Instruments included the Beck
      Cognitive Insight Scale, the Insight Scale and the Recovery Assessment Scale to
      assess the cognitive and clinical insight, and personal recovery. The
      neurocognitive assessment was represented by a single factor score produced by a
      principal components analysis of a neurocognitive test battery. Social
      functioning was measured also. Low self-reflectiveness of cognitive insight
      represented the best predictors of personal recovery. The relationship between
      cognitive insight and recovery found in this study may contribute to develop
      tailored interventions, taking into account the personal sense of recovery,
      despite the psychopathological evaluation. 

PMID- 25064089
TI  - An exploration of sexual desire and sexual activities of women with psychosis.
AB  - Sexual disturbances in patients with severe mental disorders can be related to
      medication, to psychological issues such as self-stigma and anhedonia, but also
      to the social context. This research aims to gain knowledge of desire and sexual
      practices in women suffering from schizophrenia. Women outpatients suffering from
      schizophrenia were compared with healthy women. Contrary to previous research,
      women with schizophrenia featured dyadic and individual desire similar to women
      of comparable age. Yet, only half of women with psychosis had sexual practice,
      either alone or with a partner. They were less satisfied with their activity,
      both in terms of function and psychological issues such as sexual self-esteem.
      Keeping into account the fact that most clinicians avoid this topic, this finding
      underscores the stigmatization these women suffer from, which prevents the
      opportunity of a possible improvement in this important interpersonal domain. 

PMID- 25064090
TI  - The responses of young people to their experiences of first-episode psychosis:
      harnessing resilience.
AB  - There is a burgeoning literature on first-episode psychosis, the focus of which
      is early intervention. Little emphasis has been placed on the responses of young
      people to their experiences of psychosis. This study, therefore, aimed to
      describe and explain the responses of young people to their first episode of
      psychosis. Data obtained from ten young people who attended a community early
      intervention recovery program in Perth Western Australia were analysed using a
      grounded theory method. The results revealed that the basic psychosocial problem
      experienced by participants was loss of control resulting in disrupted lives and
      that the core variable, harnessing resilience, accounted for most of the variance
      in their behaviour to overcome this problem. The resultant framework described
      and explained how participants resiled and established direction in their lives.
      Although there are limitations with this qualitative study, such as the small
      size and the demographics of the sample, the findings have potential implications
      for approaches to service provision and phase specific interventions. 

PMID- 25064091
TI  - Diversity of cultivable halophilic archaea and bacteria from superficial
      hypersaline sediments of Tunisian solar salterns.
AB  - Prokaryotes in the superficial sediments are ecologically important
      microorganisms that are responsible for the decomposition, mineralization and
      subsequent recycling of organic matter. The aim of this study was to explore the
      phylogenetic and functional diversity of halophilic archaea and bacteria isolated
      from the superficial sediments of solar salterns at Sfax, Tunisia. Sixty four
      strains were isolated from crystallizer (TS18) and non-crystallizer (M1) ponds
      and submitted to genotypic characterization and evaluation by amplified ribosomal
      RNA restriction analysis (ARDRA) techniques. Our findings revealed that the
      archaeal diversity observed for 29 isolates generated five distinct patterns from
      the non-crystallizer M1 pond, with Halorubrum chaoviator as the most prevalent
      cultivable species. However, in the TS18 crystallizer pond, ten restriction
      patterns were observed, with the prevalence of haloarchaea EB27K, a not yet
      identified genotype. The construction of a neighbour-joining tree of 16S rRNA
      gene sequences resulted in the division of the potential new species into two
      major groups, with four strains closely related to the sequence of the
      unculturable haloarchaeon EB27K and one strain to the recently described
      Halovenus aranensis strain. The 35 bacterial strains observed in this work were
      present only in the non-crystallizer pond (M1) and presented two distinct ARDRA
      patterns. These strains belonged to the gamma-proteobacteria subdivision, with
      members of Salicola marasensis (83%) being the most predominant species among the
      isolates. 16S rRNA gene sequencing revealed that Salicola strains displayed
      different degrees of homogeneity. The results from pulsed field gel
      electrophoresis assays showed that the Salicola isolates could be clustered in
      two distinct groups with different genome sizes.

PMID- 25064092
TI  - Complex reconstruction after wide excision of juvenile aponeurotic fibromatoses
      of upper one-third of leg.
AB  - Juvenile musculoaponeurotic fibromatoses are benign tumors which arise from
      musculoaponeurotic stromal cells. They rarely occur in lower extremity and more
      rarely in children. They are locally invasive tumors with a high incidence of
      recurrence after surgery. Hence, wide local excision is the treatment of choice
      for such tumors. However, complex reconstruction is often required to cover the
      resulting soft tissue defect. This report presents a 12-year-old boy with a
      juvenile musculoaponeurotic fibromatosis in the anteromedial aspect of the upper
      third of a left leg. Following wide local excision, two local flaps, medial
      gastrocnemius and a distally based peroneal artery perforator flap, were used to
      reconstruct the soft tissue defect. Reconstruction has provided an acceptable
      functional and cosmetic result. 

PMID- 25064093
TI  - A multidisciplinary rehabilitation programme improves disability, kinesiophobia
      and walking ability in subjects with chronic low back pain: results of a
      randomised controlled pilot study.
AB  - PURPOSE: To evaluate the effect of a multidisciplinary rehabilitation programme
      on disability, kinesiophobia, catastrophizing, pain, quality of life and gait
      disturbances in patients with chronic low back pain (CLBP). METHODS: This was a
      parallel-group, randomised, superiority-controlled pilot study in which 20
      patients were randomly assigned to a programme consisting of motor training
      (spinal stabilising exercises plus usual-care) and cognitive-behavioural therapy
      (experimental group, 10 subjects) or usual-care alone (control group, 10
      subjects). Before treatment, 8 weeks later (post-treatment), and 3 months after
      the end of treatment, the Oswestry Disability Index, the Tampa Scale for
      Kinesiophobia, the Pain Catastrophizing Scale, a pain numerical rating scale, and
      the Short-Form Health Survey were assessed. Spatio-temporal gait parameters were
      also measured by means of an electronic walking mat. A linear mixed model for
      repeated measures was used for each outcome measure. RESULTS: The programme had
      significant group (p = 0.027), time (p < 0.001), and time-by-group interaction (p
      < 0.001) effects on disability, with the experimental group showing an
      improvement after training of about 61 % (25 % in the control group). The
      analyses of kinesiophobia, catastrophizing, and the quality of life also revealed
      significant time, group, and time-by-group interaction effects in favour of the
      experimental group, and there was a significant effect of time on pain. Both
      groups showed a general improvement in gait parameters, with the experimental
      group increasing cadence significantly more. CONCLUSION: The multidisciplinary
      rehabilitation programme including cognitive-behavioural therapy was superior to
      the exercise programme in reducing disability, kinesiophobia, catastrophizing,
      and enhancing the quality of life and gait cadence of patients with CLBP.

PMID- 25064095
TI  - Development of pronuclear injection-based targeted transgenesis in mice through
      Cre-loxP site-specific recombination.
AB  - Microinjection of DNA into the pronuclei of zygotes is the simplest and most
      widely used method for generating transgenic (Tg) mice. However, it is always
      associated with random integration of multiple copies of the transgene, resulting
      in unstable, low, or no transgene expression due to positional effects and/or
      repeat-induced gene silencing. In addition, random integration sometimes disrupts
      an endogenous gene that can affect the phenotypes of Tg mice. Our recently
      developed pronuclear injection-based targeted transgenesis (PITT) method enables
      the integration of a single-copy transgene into a predetermined genomic locus
      through Cre-loxP site-specific recombination. The PITT method enables stable and
      reliable transgene expression in Tg mice and is also applicable for generating
      knockdown mice. Therefore, the PITT method could represent next-generation
      transgenesis that overcomes the pitfalls of conventional transgenesis. 

PMID- 25064094
TI  - Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and
      enhances CB2 gene expression in patients with chronic hepatitis C.
AB  - BACKGROUND: The aim of this study was to assess whether two-years treatment with
      Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of
      TGF-beta1, IL-6, TNF-alpha and CB1 and CB2 gene expression, in patients with
      chronic hepatitis C (CHC). METHODS: Twenty-eight patients out of 34 with CHC
      virus infection were enrolled in the study and received Pirfenidone (1200 mg/day)
      for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies
      and serum samples were obtained at the beginning and end of treatment. Modified
      HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis
      progression alongside with necroinflammation and steatosis. TGF-beta1, IL-6, TNF
      alpha and liver transaminases were measured in serum at two-months intervals. HCV
      genotype and viral load were also assessed. Quality of life was evaluated by SF36
      questionnaires and the prognosis of disease was assessed with Child-Pugh score.
      The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes.
      RESULTS: Intention to treat analyses were performed for biochemistry and clinical
      parameters. At the end of treatment, necroinflammation grading was reduced in an
      average of 3.2 points in 82% of patients (p < 0.05) and Ishak's fibrosis stage
      decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in
      61% of patients. IL-6 and TGF-beta1 serum levels decreased significantly in 93%
      and 67% of patients (p < 0.05), respectively, while TNF-alpha diminished in 47%
      of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels
      increased in 86% and CB1 expression diminished in 29% of patients. Both, quality
      of life and Child-Pugh score improvements were reported in all patients.
      CONCLUSIONS: Pirfenidone for two years benefits CHC patients and improves
      inflammation, fibrosis and steatosis in higher number of patients as previously
      shown for 12-months treatment with PFD. Additionally, PFD improved TGFbeta1 and
      IL-6 levels and diminished liver expression of anti-fibrogenic receptor CB2.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02161952. Protocol
      Registration Date: 06/11/2014.

PMID- 25064096
TI  - Generation of conditional knockout mice.
AB  - Conditional knockout mouse models are powerful tools to examine the biological
      and molecular function(s) of genes in specific tissues. The general procedure to
      generate such genetically engineered mouse models consists of three main steps.
      The first step is to find the appropriate genomic clone of the gene of interest
      and to design the cloning and Southern blot strategies. The second step is the
      cloning of the gene-targeting vector with all its essential components including
      positive and negative selection cassettes and the insertion of LoxP sites.
      Although conventional methods are still being widely used for DNA cloning, we
      describe in this book chapter the use of lambda Red phage-based homologous
      recombination in Escherichia coli to capture the genomic DNA of the gene of
      interest and to assemble the gene-targeting vector. This new method provides
      several advantages as it does not require the presence of restriction sites
      within the gene of interest to insert LoxP-flanked DNA fragments. In the final
      step, the gene-targeting vector is transferred into embryonic stem (ES) cells,
      and successfully targeted ES cell clones are injected into mouse blastocysts to
      generate conditional knockout mice.

PMID- 25064097
TI  - Generating mouse lines for lineage tracing and knockout studies.
AB  - In 2007 Capecchi, Evans, and Smithies received the Nobel Prize in recognition for
      discovering the principles for introducing specific gene modifications in mice
      via embryonic stem cells, a technology, which has revolutionized the field of
      biomedical science allowing for the generation of genetically engineered animals.
      Here we describe detailed protocols based on and developed from these ground
      breaking discoveries, allowing for the modification of genes not only to create
      mutations to study gene function but additionally to modify genes with
      fluorescent markers, thus permitting the isolation of specific rare wild-type and
      mutant cell types for further detailed analysis at the biochemical, pathological,
      and genomic levels.

PMID- 25064098
TI  - Generation of an allelic series of knock-in mice using recombinase-mediated
      cassette exchange (RMCE).
AB  - Molecular genetic strategies applying embryonic stem cell (ES cell) technologies
      to study the function of a gene in mice or to generate a mouse model for a human
      disease are continuously under development. Next to (conditional) inactivation of
      genes the application and importance of approaches to generate knock-in mutations
      are increasing. In this chapter the principle and application of recombinase
      mediated cassette exchange (RMCE) are discussed as being a new emerging knock-in
      strategy, which enables easy generation of a series of different knock-in
      mutations within one gene. An RMCE protocol, which was used to generate a series
      of different knock-in mutations in the Lrp1 gene of ES cells, is described in
      detail as an example of how RMCE can be used to generate highly efficiently an
      allelic series of differently modified ES cell clones from a parental modified ES
      cell clone. Subsequently the differently modified ES cell clones can be used to
      generate an allelic series of mutant knock-in mice.

PMID- 25064099
TI  - Generating chimeric mice from embryonic stem cells via vial coculturing or
      hypertonic microinjection.
AB  - The generation of a fertile embryonic stem cell (ESC)-derived or F0 (100 % coat
      color chimerism) mice is the final criterion in proving that the ESC is truly
      pluripotent. Many methods have been developed to produce chimeric mice. To date,
      the most popular methods for generating chimeric embryos is well sandwich
      aggregation between zona pellucida (ZP) removed (denuded) 2.5-day post-coitum
      (dpc) embryos and ESC clumps, or direct microinjection of ESCs into the cavity
      (blastocoel) of 3.5-dpc blastocysts. However, due to systemic limitations and the
      disadvantages of conventional microinjection, aggregation, and coculturing, two
      novel methods (vial coculturing and hypertonic microinjection) were developed in
      recent years at my laboratory.Coculturing 2.5-dpc denuded embryos with ESCs in
      1.7-mL vials for ~3 h generates chimeras that have significantly high levels of
      chimerism (including 100 % coat color chimerism) and germline transmission. This
      method has significantly fewer instrumental and technological limitations than
      existing methods, and is an efficient, simple, inexpensive, and reproducible
      method for "mass production" of chimeric embryos. For laboratories without a
      microinjection system, this is the method of choice for generating chimeric
      embryos. Microinjecting ESCs into a subzonal space of 2.5-dpc embryos can
      generate germline-transmitted chimeras including 100 % coat color chimerism.
      However, this method is adopted rarely due to the very small and tight space
      between ZP and blastomeres. Using a laser pulse or Piezo-driven instrument/device
      to help introduce ESCs into the subzonal space of 2.5-dpc embryos demonstrates
      the superior efficiency in generating ESC-derived (F0) chimeras. Unfortunately,
      due to the need for an expensive instrument/device and extra fine skill, not many
      studies have used either method. Recently, ESCs injected into the large subzonal
      space of 2.5-dpc embryos in an injection medium containing 0.2-0.3 M sucrose very
      efficiently generated viable, healthy, and fertile chimeric mice with 100 % coat
      color chimerism.Both vial coculture and hypertonic microinjection methods are
      useful and effective alternatives for producing germline chimeric or F0 mice
      efficiently and reliably. Furthermore, both novel methods are also good for
      induced pluripotent stem cells (iPSCs) to generate chimeric embryos. 

PMID- 25064100
TI  - Genetic inducible fate mapping in adult mice using tamoxifen-dependent Cre
      recombinases.
AB  - The Cre/lox site-specific recombination system allows the control of gene
      activity in space and time in almost any tissue of the mouse. A major technical
      advance was the development of tamoxifen-dependent Cre recombinases, such as
      CreER(T2), that can be activated by administration of tamoxifen to the animal.
      This powerful tool greatly facilitates the study of gene functions and the
      generation of more realistic animal models of sporadic human diseases. Another
      important application of tamoxifen-dependent Cre recombinases is genetic
      inducible fate mapping (GIFM). In GIFM studies, the inducible Cre/lox system is
      used to genetically label a defined cell population at a selected time by
      irreversible activation of the expression of a Cre-responsive reporter transgene.
      Then, marked cells are detected at later time points to determine how the
      originally labeled progenitors contribute to specific structures and cell types
      during pre- and postnatal development. GIFM was initially applied during mouse
      embryogenesis, but is now increasingly used for cell lineage tracing in adult
      mice under physiological and pathophysiological conditions. Here we describe the
      design of GIFM experiments in adult mice as exemplified by CreER(T2)-assisted
      tracing of vascular smooth muscle cells during the development of atherosclerotic
      lesions. First, we give an overview of reporter transgenes available for genetic
      cell marking that are expressed from the Rosa26 locus, such as beta-galactosidase
      and fluorescent proteins. Then we present detailed protocols for the generation
      of experimental mice for GIFM studies, the induction of cell labeling by
      tamoxifen treatment, and the detection of marked cells in fixed and live tissues.
      Each section also provides a discussion of limitations and common pitfalls of
      GIFM experiments. Most of the protocols can be easily adapted to other
      developmental stages, cell types, Cre recombinases, and reporter transgenes and,
      thus, can be used as general guidelines for GIFM studies in mice. 

PMID- 25064101
TI  - Intracytoplasmic sperm injection (ICSI)-mediated transgenesis in mice.
AB  - Over the years many well-described techniques for the introduction of transgene
      DNA into host organisms have been used, including pronuclear injection, in vitro
      fertilization-mediated transgenesis, transfection of ES and spermatogenic cells,
      nuclear transfer of somatic cell nuclei, and lentiviral vectors. The application
      of these techniques has been limited however either by the time and effort to be
      executed or by their narrow efficiency with large transgenes. The greatest
      advantage of intracytoplasmic sperm injection (ICSI)-mediated transgenesis is
      precisely its ability to stably introduce large DNA molecules into the genome of
      host organisms with relatively high efficiency, as compared to alternative
      procedures. In mice, this procedure has been shown to be a reproducible method to
      generate transgenic offspring with a high efficiency. Recently, it proved also to
      be a viable method to generate transgenic rats and pigs, and as such, it is
      foreseen with great interest for the production of transgenic farm animals, where
      it would constitute an important tool for the production of recombinant proteins
      and livestock improvement. 

PMID- 25064102
TI  - Generation of bacterial artificial chromosome (BAC) transgenic mice.
AB  - Transgenic mice are among the most helpful tools to study the role of genes in
      physiological conditions. In this protocol, we describe the generation of
      bacterial artificial chromosome (BACs) constructs, which are used to express a
      gene of interest under a particular promoter. BACs as driver of transgenes have
      the advantage that a characterization of transcriptional control elements is
      unnecessary and the construct's size usually reduces position effects from random
      integration. In the following, we firstly explain in detail the amplification of
      the BAC, the generation of the targeting construct as well as the recombination
      by ET-cloning, and the analysis of the recombined clones by Southern blot
      analysis. Finally, we also describe the preparation of the BACs for oocyte
      injection. In total, the construction of such BAC transgenes needs around 6-8
      weeks. 

PMID- 25064103
TI  - Generation of genetically engineered mice by the piggyBac transposon system.
AB  - Genetically engineered mice (GEM) are invaluable tools not only for understanding
      mammalian biology but also for modeling human diseases. Here we present protocols
      to generate GEM with the piggyBac (PB) transposon system. In the first part, we
      describe a transgenic procedure that co-injects the transgene carried by a PB
      donor plasmid and a PB transposase (PBase)-expressing helper plasmid into the
      pronuclei of fertilized eggs. In the second part, we provide a large-scale, cost
      effective insertional mutagenesis strategy that remobilizes single-copy PB
      transposons in the male germ line. Given that PB can transpose in a broad
      spectrum of eukaryotic hosts, the protocols described here could be adapted for
      other species in the future. 

PMID- 25064104
TI  - Generation and applications of MADM-based mouse genetic mosaic system.
AB  - Genetic mosaics describe organisms that contain cells with distinct genotypes
      related to somatic transposition, mitotic recombination, or genomic aberrations.
      Most, if not all, human cancers are genetic mosaics because cancer cells bear
      mutations that are absent in normal cells within the same body. While naturally
      occurring mutant cells in genetic mosaic animals are difficult to track down, a
      genetically engineered mosaic mouse model termed MADM (Mosaic Analysis with
      Double Markers) enables one to perform phenotypic analysis of mutant cells at
      single-cell resolution in vivo. While cancer modeling is the most obvious
      application, MADM is also highly suitable for studying developmental biology,
      neuroscience, and regenerative biology problems to investigate clonal
      contributions. Here we describe the construction of the MADM model on a specific
      chromosome through ES cell-based targeting of MADM cassettes into a pair of
      homologous chromosomes. We also detail procedures to verify the labeling
      efficiency of the newly established MADM model. Finally, we explain the breeding
      schemes and analytical principles that enable using MADM for in vivo phenotypic
      analysis at single-cell resolution. 

PMID- 25064105
TI  - Generation of mouse lines conditionally over-expressing microRNA using the Rosa26
      Lox-Stop-Lox system.
AB  - MicroRNAs are currently the object of intensive investigation due to their role
      in a myriad of physiological processes and pathological conditions, such as gene
      regulation and tumorigenesis. To better understand microRNA function, numerous
      laboratories have already taken advantage of the available techniques of genome
      editing in mouse. Here, we describe how to generate genetically engineered mouse
      lines using the popular Rosa-26 Lox-Stop-Lox Knock-In (Rosa-LSL-KI) targeting.
      This strategy allows for the selective overexpression of microRNAs of interest
      when coupled to a tissue-specific Cre-expressing line. The present protocol
      illustrates in detail both the engineering of the targeting vector and the
      generation of mutated ES clones ready for injection into mouse blastocysts. 

PMID- 25064106
TI  - In situ hybridization (both radioactive and nonradioactive) and spatiotemporal
      gene expression analysis.
AB  - Section in situ hybridization using either radioactive or nonradioactive labeled
      cDNA probes is an invaluable technique that enables the investigator to detect
      and localize mRNA expression within tissue sections and cells. Here, we describe
      the labeling of (35)S-UTP radioactive and nonradioactive digoxigenin probes,
      preparation of tissue sections, hybridization, and washing of non-hybridized
      probes, followed by the detection of radioactive signals via dipping in nuclear
      emulsion and the immunohistochemical and subsequent colorimetric detection of
      nonradioactive signals. 

PMID- 25064107
TI  - Isolation and handling of mouse embryonic fibroblasts.
AB  - Primary mouse embryonic fibroblasts (MEFs) are the most commonly used feeder
      layers that help to support growth and maintain pluripotency of embryonic stem
      cells (ESC) in long-term culture. Feeders provide substrates/nutrients that are
      essential to maintain pluripotency and prevent spontaneous differentiation of
      ESC. Since embryonic fibroblasts stop dividing after a few passages, care must be
      taken to isolate them freshly. Here, we provide a protocol to derive MEFs and
      describe the method to inactivate the cells using mitomycin C treatment. The
      protocol also describes freezing, thawing, and passaging of MEFs. This basic
      protocol works well in our laboratory. However, it can be modified and adapted
      according to any user's particular requirement.

PMID- 25064108
TI  - Generation of induced pluripotent stem cells from mouse adipose tissue.
AB  - The discovery that embryonic stem (ES) cell-like cells can be generated by simply
      over-expressing four key genes in adult somatic cells has changed the face of
      regenerative medicine. These induced pluripotent stem (iPS) cells have a wide
      range of potential uses from drug testing and in vitro disease modeling to
      personalized cell therapies for patients. However, prior to the realization of
      their potential, many issues need to be considered. One of these is the low
      efficiency formation of iPSC. It has been extensively demonstrated that the
      somatic cell type can greatly influence reprogramming outcomes. We have shown
      that adipose tissue-derived cells (ADCs) can be easily isolated from adult
      animals and can be reprogrammed to a pluripotent state with high efficiency.
      Here, we describe a protocol for the high-efficiency derivation of ADCs and their
      subsequent use to generate mouse iPSC using Oct4, Sox2, Klf4, and cMyc retroviral
      vectors.

PMID- 25064109
TI  - Pdx1 (GFP/w) mice for isolation, characterization, and differentiation of
      pancreatic progenitor cells.
AB  - It is well known that human cells are diverse with respect to their epigenome,
      transcriptome, and proteome. In the context of regenerative medicine, it is
      important for the transplanted cells or tissues to faithfully recapitulate their
      intended tissue type in each of these respects. Whether the cells chosen for such
      an application are embryonic, postnatal, or induced pluripotent stem cells, the
      transplanted product must behave in a predictable and reliable manner to be a
      safe and effective treatment option. Irrespective of the choice of cells used in
      such an application, the characterization and understanding of the developmental
      cues responsible for establishing and maintaining the desired cell phenotype are
      essential.Animal models are extremely important in understanding the development
      of a specific tissue, which can then be subsequently extrapolated to human
      studies. Generation of transgenic animal models with whole-body gene knockout,
      conditional knockout, constitutive fluorescent gene reporters, and Cre-Lox-based
      conditional and lineage reporters has revolutionized the field of developmental
      biology. An intrinsically complex network of the actions and interactions of the
      multitude of different signalling cascades is required for development. A
      thorough understanding of such networks, gained through studies on transgenic
      animal models, is essential for the development of the techniques necessary to
      reliably differentiate a given stem or progenitor cell population into a specific
      cell type, such as an islet-like, insulin-producing cell aggregate.In this
      chapter, we describe the use of GFP (green fluorescent protein)-based reporter
      mice for isolation of cells of choice, analyzing gene expression in those cells
      as well as their use for screening signalling molecules to understand their
      effect on differentiation. 

PMID- 25064111
TI  - Analyzing gene function in adult long-term hematopoietic stem cells using the
      interferon inducible Mx1-Cre mouse system.
AB  - Long-term hematopoietic stem cells (LT-HSCs) have the ability to self-renew and
      differentiate into all blood cell lineages. Understanding the genetic networks
      that regulate LT-HSC function in the adult bone marrow requires inducible gene
      targeting and bone marrow transplantations. In this chapter we describe the use
      of the inducible Mx1-Cre mouse model to delete genes in LT-HSCs and methodologies
      for examining the function of LT-HSCs following deletion.

PMID- 25064112
TI  - Generation of transgenic mice by exploiting spermatogonial stem cells in vivo.
AB  - The protocols in this chapter describe two techniques for the generation of
      transgenic mice by in vivo manipulation of spermatogonial stem cells (SSCs) with
      a high rate of success. SSCs in prepubescent animals can either be infected in
      vivo with recombinant lentiviruses expressing the transgene of interest or DNA
      can be injected into the testis followed by the application of an electric
      current resulting in integration of the linearized DNA containing a transgene
      downstream of the appropriate promoter into SSCs. All male pre-founder mice
      produced transgenic pups using both protocols with the transgene being heritable.
      Further, the pre-founder mice could be used in multiple mating experiments
      resulting in the generation of multiple progeny. These protocols could be
      extended to perform over-expression/knockdown screens in vivo using bar-coded
      lentiviruses/plasmid constructs, thus permitting the design of genetic screens in
      the mouse. Further, these protocols could be adapted to achieve transgenesis in
      other laboratory animals resulting in the generation of model systems that
      closely approximate human development and disease. 

PMID- 25064110
TI  - Generation of transgenic mouse fluorescent reporter lines for studying
      hematopoietic development.
AB  - During the development of the hematopoietic system, at least eight distinct
      lineages are generated in the mouse embryo. Transgenic mice expressing
      fluorescent proteins at various points in the hematopoietic hierarchy, from
      hematopoietic stem cell to multipotent progenitors to each of the final
      differentiated cell types, have provided valuable tools for tagging, tracking,
      and isolating these cells. In this chapter, we discuss general considerations in
      designing a transgene and survey available fluorescent probes and methods for
      confirming and analyzing transgene expression in the hematopoietic systems of the
      embryo, fetus, and postnatal/adult animal. 

PMID- 25064113
TI  - Methods for the detection of genome instability derived from replication stress
      in primary mouse embryonic fibroblasts.
AB  - Replication stress, with its subsequent genome instability, is a hallmark of
      cancer from its earliest stages of development. Here, we describe assays that are
      sufficiently sensitive to detect intrinsic replicative stress and its
      consequences in primary mouse embryonic fibroblasts. First, we explain the non
      denatured DNA fiber assay, a powerful tool to directly measure DNA replication
      kinetics via the dual-labeling of active replication forks. Then, we describe the
      cytokinesis-block micronucleus assay, which can be combined with detection of
      53BP1 nuclear bodies to measure the levels of replication-associated genome
      instability carried over into G1 phase of the cell cycle. 

PMID- 25064114
TI  - Transgenic nude mice ubiquitously expressing fluorescent proteins for color-coded
      imaging of the tumor microenvironment.
AB  - We have developed a transgenic green fluorescent protein (GFP) nude mouse with
      ubiquitous GFP expression. The GFP nude mouse was obtained by crossing
      nontransgenic nude mice with the transgenic C57/B6 mouse in which the beta-actin
      promoter drives GFP expression in essentially all tissues. In the adult mice,
      many organs brightly expressed GFP, including the spleen, heart, lungs, spleen,
      pancreas, esophagus, stomach, and duodenum as well as the circulatory system. The
      liver expressed GFP at a lesser level. The red fluorescent protein (RFP)
      transgenic nude mouse was obtained by crossing non-transgenic nude mice with the
      transgenic C57/B6 mouse in which the beta-actin promoter drives RFP (DsRed2)
      expression in essentially all tissues. In the RFP nude mouse, the organs all
      brightly expressed RFP, including the heart, lungs, spleen, pancreas, esophagus,
      stomach, liver, duodenum, the male and female reproductive systems; brain and
      spinal cord; and the circulatory system, including the heart, and major arteries
      and veins. The skinned skeleton highly expressed RFP. The bone marrow and spleen
      cells were also RFP positive. The cyan fluorescent protein (CFP) nude mouse was
      developed by crossing nontransgenic nude mice with the transgenic CK/ECFP mouse
      in which the beta-actin promoter drives expression of CFP in almost all tissues.
      In the CFP nude mice, the pancreas and reproductive organs displayed the
      strongest fluorescence signals of all internal organs, which vary in intensity.
      The GFP, RFP, and CFP nude mice when transplanted with cancer cells of another
      color are powerful models for color-coded imaging of the tumor microenvironment
      (TME) at the cellular level.

PMID- 25064115
TI  - Genetically engineered insertional mutagenesis in mice to model cancer: Sleeping
      Beauty.
AB  - The ability to accurately model human cancer in mice enables in vivo examination
      of the biological mechanisms related to cancer initiation and progression as well
      as preclinical testing of new anticancer treatments and potential targets. The
      emergence of the genetically engineered Sleeping Beauty system of insertional
      mutagenesis has led to the development of a new generation of genetic mouse
      models of cancer and identification of novel cancer-causing genes. This chapter
      reviews the published cancer models of Sleeping Beauty and strategies using
      available strains to generate several models of cancer. 

PMID- 25064116
TI  - Generating double knockout mice to model genetic intervention for diabetic
      cardiomyopathy in humans.
AB  - Diabetes is a rapidly increasing disease that enhances the chances of heart
      failure twofold to fourfold (as compared to age and sex matched nondiabetics) and
      becomes a leading cause of morbidity and mortality. There are two broad
      classifications of diabetes: type1 diabetes (T1D) and type2 diabetes (T2D).
      Several mice models mimic both T1D and T2D in humans. However, the genetic
      intervention to ameliorate diabetic cardiomyopathy in these mice often requires
      creating double knockout (DKO). In order to assess the therapeutic potential of a
      gene, that specific gene is either overexpressed (transgenic expression) or
      abrogated (knockout) in the diabetic mice. If the genetic mice model for diabetes
      is used, it is necessary to create DKO with transgenic/knockout of the target
      gene to investigate the specific role of that gene in pathological cardiac
      remodeling in diabetics. One of the important genes involved in extracellular
      matrix (ECM) remodeling in diabetes is matrix metalloproteinase-9 (Mmp9). Mmp9 is
      a collagenase that remains latent in healthy hearts but induced in diabetic
      hearts. Activated Mmp9 degrades extracellular matrix (ECM) and increases matrix
      turnover causing cardiac fibrosis that leads to heart failure. Insulin2 mutant
      (Ins2+/-) Akita is a genetic model for T1D that becomes diabetic spontaneously at
      the age of 3-4 weeks and show robust hyperglycemia at the age of 10-12 weeks. It
      is a chronic model of T1D. In Ins2+/- Akita, Mmp9 is induced. To investigate the
      specific role of Mmp9 in diabetic hearts, it is necessary to create diabetic mice
      where Mmp9 gene is deleted. Here, we describe the method to generate Ins2+/-/Mmp9
      /- (DKO) mice to determine whether the abrogation of Mmp9 ameliorates diabetic
      cardiomyopathy.

PMID- 25064117
TI  - Experimental osteoarthritis models in mice.
AB  - Osteoarthritis (OA) is a slowly progressing, degenerative disorder of synovial
      joints culminating in the irreversible destruction of articular cartilage and
      subchondral bone. It affects almost everyone over the age of 65 and influences
      life quality of affected individuals with enormous costs to the health care
      system. Current therapeutic strategies seek to ameliorate pain and increase
      mobility; however, to date none of them halts disease progression or regenerates
      damaged cartilage or bone. Thus, there is an ultimate need for the development of
      new, noninvasive treatments that could substitute joint replacement for late- or
      end-stage patients. Therefore, osteoarthritis animal models for mimicking of all
      OA features are important. Mice develop an OA pathology that is comparable to
      humans, rapidly develop OA due to the short lifetime and show reproducible OA
      symptoms. They provide a versatile and widely used animal model for analyzing
      molecular mechanisms of OA pathology. One major advantage over large animal
      models is the availability of knockout or transgenic mice strains to examine
      genetic predispositions/contributions to OA.In this chapter, we describe three
      widely used instability-inducing murine osteoarthritis models. The most common
      two methods for surgical induction are: (1) destabilization of the medial
      meniscus (DMM) and (2) anterior cruciate ligament transection (ACLT). In the DMM
      model, the medial meniscotibial ligament is transected while in the ACLT model
      the anterior cruciate ligament is destroyed. In the third, chemical induced
      instability method, intraarticular collagenase is injected into the knee joint.
      Intraarticular collagenase weakens articular ligaments which cause instability of
      the joint, and full-blown OA develops within 6 weeks. For morphological
      evaluation, we correspond mainly to the recommendations of OARSI for histological
      assessment of osteoarthritis in mouse. For statistical evaluation summed or mean
      scores of all four knee areas (medial tibial plateau (MTP), medial tibial condyle
      (MFC), lateral tibial plateau (LTP) or lateral femoral condyle (LFC)), medial
      and/or lateral regions are used.In future, not only large animal models like
      guinea pigs, sheep, goats, or horses will be important for a better understanding
      of osteoarthritis, but especially the mouse model with its rapid development of
      osteoarthritis and its numerous advantages by providing knockout or transgenic
      strains will become more and more relevant for drug development and determination
      of genetic predispositions of osteoarthritis pathology.

PMID- 25064118
TI  - Mouse models and methods for studying human disease, acute kidney injury (AKI).
AB  - Acute kidney injury (AKI) is serious complication in hospitalized patients with
      high level of mortality. There is not much progress made for the past 50 years in
      reducing the mortality rate despite advances in understanding disease pathology.
      Using variety of animal models of acute kidney injury, scientist studies the
      pathogenic mechanism of AKI and to test therapeutic drugs, which may reduce renal
      injury. Among them, renal pedicle clamping and cisplatin induced nephrotoxicity
      in mice are most prominently used, mainly due to the availability of gene
      knockouts to study specific gene functions, inexpensive and availability of the
      inbred strain with less genetic variability. However, ischemic mouse model is
      highly variable and require excellent surgical skills to reduce variation in the
      observation. In this chapter, we describe a detailed protocol of the mouse model
      of bilateral renal ischemia-reperfusion and cisplatin induced nephrotoxicity. We
      also discuss the protocol for the isolation and analysis of infiltrated
      inflammatory cell into the kidney by flow cytometry. Information provided in this
      chapter will help scientist who wants to start research on AKI and want to
      establish the mouse model for ischemic and toxic kidney injury. 

PMID- 25064119
TI  - Mouse models of acute and chronic colitis.
AB  - Crohn's disease (CD) and ulcerative colitis are two main clinically defined forms
      of chronic inflammatory bowel disease (IBD). Our understanding of IBD depends
      largely on rodent models. DSS-induced intestinal inflammation in mice and T cell
      transfer colitis in SCID mice are most widely used and accepted models that can
      recapitulate the human diseases. Here, we provide detailed protocols of these two
      mouse models of experimentally induced intestinal inflammation. We also discuss
      the protocols for the isolation and analysis of inflammatory T cell from the
      colon. 

PMID- 25064120
TI  - Manipulation and assessment of gut microbiome for metabolic studies.
AB  - The mammalian gut is inhabited by a complex and highly diverse population of
      bacteria. About 100 trillion microbes are present in the human gut, a number ten
      times more than the total number of cells in an adult human body. These
      microorganisms play an important role in several fundamental and crucial
      processes such as immunity, digestion, synthesis of vitamins, and metabolizing
      bile acids, sterols, and xenobiotics in the host, thereby influencing human
      health. Identification and manipulation of these metabolic interfaces is
      therefore critical. Here, we present a set of methods for manipulation and
      targeting the 16S rRNA based identification of rodent gut microbiota using
      Sanger's and next-generation sequencing platforms. Novel methods for manipulation
      of gut microbiota are also presented. In principle, these methods can be easily
      adapted to most rodent models for successful screening and manipulation of gut
      microbiome, to generate a better understanding of their role in metabolic
      disease. 

PMID- 25064121
TI  - The association of effort-reward imbalance and asthma: findings from two cross
      sectional studies.
AB  - PURPOSE: There is evidence to suggest that work stress is positively associated
      with the occurrence of asthma. A limitation is that the small number of prior
      studies utilized unestablished work stress measures, thus constraining
      interpretation and generalizability. The present study re-examined this
      association by assessing work stress based on the well-established effort-reward
      imbalance (ERI) model. METHODS: We drew on data from two cross-sectional studies.
      Study 1 was conducted in a large pharmaceutical company in 2013 (n = 1,464).
      Study 2 was based on data from the 2011 wave of the population-based German Socio
      Economic Panel (n = 8,388). ERI was assessed by validated questionnaires. Asthma
      was determined by self-report of a physician-based diagnosis. Associations
      between ERI or its subcomponents "effort", "reward" and "overcommitment" (z
      scores or categorized) with asthma were estimated by logistic regression models
      and reported as adjusted odds ratios (ORs) with 95 % confidence intervals (CIs).
      RESULTS: A one standard deviation increase of the ERI score (reflecting higher
      work stress) was associated with a 22-48 % elevated odds of asthma (Study 1: OR
      1.48, 95 % CI 1.13-1.95, and Study 2: OR 1.22, 95 % CI 1.10-1.36). Z score-based
      analyses of the separate ERI components generally suggested moderate associations
      of effort, reward and overcommitment with asthma in both studies (Study 1: OR
      effort 1.25, 95 % CI 0.95-1.64, OR reward 0.67, 95 % CI 0.51-0.87, OR
      overcommitment 1.32, 95 % CI 1.01-1.72; and Study 2: OR effort 1.21, 95 % CI 1.09
      1.34, OR reward 0.83, 95 % CI 0.76-0.92, OR overcommitment 1.12, 95 % CI 1.01
      1.25). Analyses of categorized exposures largely confirmed these observations.
      CONCLUSIONS: This is the first study to demonstrate a link between an established
      work stress measure and asthma. Longitudinal studies are needed to determine the
      direction of these associations.

PMID- 25064122
TI  - Computer-based simulation training in emergency medicine designed in the light of
      malpractice cases.
AB  - BACKGROUND: Using computer-based simulation systems in medical education is
      becoming more and more common. Although the benefits of practicing with these
      systems in medical education have been demonstrated, advantages of using computer
      based simulation in emergency medicine education are less validated. The aim of
      the present study was to assess the success rates of final year medical students
      in doing emergency medical treatment and evaluating the effectiveness of computer
      based simulation training in improving final year medical students' knowledge.
      METHODS: Twenty four Students trained with computer-based simulation and
      completed at least 4 hours of simulation-based education between the dates Feb 1,
      2010 - May 1, 2010. Also a control group (traditionally trained, n =24) was
      chosen. After the end of training, students completed an examination about 5
      randomized medical simulation cases. RESULTS: In 5 cases, an average of 3.9
      correct medical approaches carried out by computer-based simulation trained
      students, an average of 2.8 correct medical approaches carried out by
      traditionally trained group (t = 3.90, p < 0.005). We found that the success of
      students trained with simulation training in cases which required complicated
      medical approach, was statistically higher than the ones who didn't take
      simulation training (p <= 0.05). CONCLUSIONS: Computer-based simulation training
      would be significantly effective in learning of medical treatment algorithms. We
      thought that these programs can improve the success rate of students especially
      in doing adequate medical approach to complex emergency cases.

PMID- 25064123
TI  - Hemostatic agents used for nephrostomy tract closure after tubeless PCNL: a
      systematic review and meta-analysis.
AB  - To evaluate the role of hemostatic agents used for nephrostomy tract closure
      after tubeless percutaneous nephrolithotomy (PCNL). A systematic review of
      Pubmed, Embase and Cochrane was performed. All studies that compared hemostatic
      agents with common methods (silk stitch or pressure dressing) were included. The
      analyzed outcomes were hospital stay, operative time, blood loss, transfusion
      rate, fever rate, and complication rate. A total of eight articles including six
      RCTs met our criteria. Hemostatic agents showed short hospital stay (MD -4.54, 95
      % CI -6.78 to -2.36, p < 0.0001). There was no difference between hemostatic
      agents and common methods on operative time (MD 2.00, 95 % CI -17.32 to 21.33, p
      = 0.84), blood loss (MD -0.19, 95 % CI -0.41 to 0.03, p = 0.08), transfusion rate
      (OR 1.42, 95 % CI 0.34-5.96, p = 0.63), fever rate (OR 1.02, 95 % CI 0.33-3.12, p
      = 0.97) and complication rate (OR 1.02, 95 % CI 0.33-3.12, p = 0.97). Eight
      studies including six RCTs showed that use of hemostatic agents was safe.
      Hemostatic agents showed short hospital stay. There were no difference between
      hemostatic agents and common methods on blood loss, transfusion rate, fever rate,
      and complication rate.

PMID- 25064124
TI  - Association of the pattern recognition molecule H-ficolin with incident
      microalbuminuria in an inception cohort of newly diagnosed type 1 diabetic
      patients: an 18 year follow-up study.
AB  - AIMS/HYPOTHESIS: Increasing evidence links complement activation through the
      lectin pathway to diabetic nephropathy. Adverse complement recognition of
      proteins modified by glycation has been suggested to trigger complement auto
      attack in diabetes. H-ficolin (also known as ficolin-3) is a pattern recognition
      molecule that activates the complement cascade on binding to glycated surfaces,
      but the role of H-ficolin in diabetic nephropathy is unknown. We aimed to
      investigate the association between circulating H-ficolin levels and the
      incidence of microalbuminuria in type 1 diabetes. METHODS: We measured baseline H
      ficolin levels and tracked the development of persistent micro- and
      macroalbuminuria in a prospective 18 year observational follow-up study of an
      inception cohort of 270 patients with newly diagnosed type 1 diabetes. RESULTS:
      Patients were followed for a median of 18 years (range 1-22 years). During follow
      up, 75 patients developed microalbuminuria, defined as a persistent urinary
      albumin excretion rate (UAER) above 30 mg/24 h. When H-ficolin levels were
      divided into quartile groups an unadjusted Cox proportional hazards regression
      model showed a significant association with risk of incident microalbuminuria
      during follow-up (HR, fourth vs first quartile, 2.45; 95% CI 1.24, 4.85) (p =
      0.01). This remained significant after adjusting for HbA1c, systolic blood
      pressure, smoking and baseline UAER (HR 2.09; 95% CI 1.03, 4.25) (p = 0.04).
      CONCLUSIONS/INTERPRETATION: Our data suggest that high levels of the complement
      activating molecule H-ficolin are associated with an increased risk of future
      progression to microalbuminuria in patients with newly diagnosed type 1 diabetes.

PMID- 25064125
TI  - Central prolactin receptors (PRLRs) regulate hepatic insulin sensitivity in mice
      via signal transducer and activator of transcription 5 (STAT5) and the vagus
      nerve.
AB  - AIMS/HYPOTHESIS: Recent studies have revealed the crucial role of the central
      nervous system (CNS), especially the hypothalamus, in the regulation of insulin
      sensitivity in peripheral tissues. The aim of our current study was to
      investigate the possible involvement of hypothalamic prolactin receptors (PRLRs)
      in the regulation of hepatic insulin sensitivity. METHODS: We employed
      overexpression of PRLRs in mouse hypothalamus via intracerebroventricular
      injection of adenovirus expressing PRLR and inhibition of PRLRs via adenovirus
      expressing short-hairpin RNA (shRNA) specific for PRLRs in vivo. Selective
      hepatic vagotomy was employed to verify the important role of the vagus nerve in
      mediating signals from the brain to peripheral organs. In addition, a genetic
      insulin-resistant animal model, the db/db mouse, was used in our study to
      investigate the role of hypothalamic PRLRs in regulating whole-body insulin
      sensitivity. RESULTS: Overexpression of PRLRs in the hypothalamus improved
      hepatic insulin sensitivity in mice and inhibition of hypothalamic PRLRs had the
      opposite effect. In addition, we demonstrated that hypothalamic PRLR-improved
      insulin sensitivity was significantly attenuated by inhibiting the activity of
      signal transducer and activator of transcription 5 (STAT5) in the CNS and by
      selective hepatic vagotomy. Finally, overexpression of PRLRs significantly
      ameliorated insulin resistance in db/db mice. CONCLUSIONS/INTERPRETATION: Our
      study identifies a novel central pathway involved in the regulation of hepatic
      insulin sensitivity, mediated by hypothalamic PRLR/STAT5 signalling and the vagus
      nerve, thus demonstrating an important role for hypothalamic PRLRs under
      conditions of insulin resistance.

PMID- 25064126
TI  - Intracellular calcium regulates nonsense-mediated mRNA decay.
AB  - The nonsense-mediated mRNA decay (NMD) pathway selectively eliminates aberrant
      transcripts containing premature translation termination codons and regulates the
      levels of a number of physiological mRNAs. NMD modulates the clinical outcome of
      a variety of human diseases, including cancer and many genetic disorders, and may
      represent a target for therapeutic intervention. Here, we have developed a new
      multicolored bioluminescence-based reporter system that can specifically and
      effectively assay NMD in live human cells. Using this reporter system, we
      conducted a robust high-throughput small-molecule screen in human cells and,
      unpredictably, identified a group of cardiac glycosides, including ouabain and
      digoxin, as potent inhibitors of NMD. Cardiac glycoside-mediated effects on NMD
      are dependent on binding and inhibiting the sodium-potassium ATPase on the plasma
      membrane and subsequent elevation of intracellular calcium levels. Induction of
      calcium release from the endoplasmic reticulum also leads to inhibition of NMD.
      Thus, this study reveals intracellular calcium as a key regulator of NMD and has
      implications for exploiting NMD in the treatment of disease. 

PMID- 25064129
TI  - Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus:
      analyses of molecular genetic characteristics of the patient and the tumor. A
      single-case study.
AB  - PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a
      choroid plexus papilloma of the brain was studied at the Hospital Infantil de
      Mexico Federico Gomez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive
      papilloma of the third ventricle was evidenced on CT and MR images and removed.
      Pathological analysis confirmed its origin. A posterior radiosurgery was required
      due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents
      undertaken at HIMFG were normal. Array comparative genomic hybridization (array
      CGH) analyses of blood DNA of the patient and her parents carried out at
      BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes
      SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient.
      Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of
      cancer and metastases of tumors, further fluorescent in situ hybridization (FISH)
      analyses of these two genes were implemented at HIMFG. Amplification of the two
      genes was found in the tumor of the case under study but not in an unrelated
      papilloma of the choroid plexus. DISCUSSION: Further analyses of the association
      of choroid plexus papillomas with disorders of psycho-neural development and its
      relationship to molecular genetic modifications at chromosome 17p are now under
      way at HIMFG.

PMID- 25064130
TI  - Can procalcitonin be used to distinguish between disease flare and infection in
      patients with systemic lupus erythematosus: a systematic literature review.
AB  - Distinction between infection and febrile disease flare in patients with systemic
      lupus erythematosus (SLE) is fundamental but often difficult to make, because
      clinical presentation can be similar. A systematic review of all articles indexed
      in PubMed through October 2013 was performed, in order to examine the potential
      role of procalcitonin (PCT) for the discrimination between SLE flare and
      infection. Among the 12 papers identified, 5 articles reported on PCT levels in
      SLE patients without infection, 6 compared PCT levels between SLE patients with
      flare versus those with infection, and 1 analyzed PCT levels in active patients
      with and without bacterial infection. These data suggest the absence of
      correlation between PCT levels and SLE disease activity. Furthermore, PCT levels
      detected during disease flares are lower than those observed during bacterial
      infections. PCT can therefore be used accurately in the early differentiation
      between bacterial infection and flare in febrile SLE patients. Raised PCT levels
      >=0.5 MUg/L should strongly suggest bacterial infection in the context of SLE,
      keeping in mind the limited data available in case of hemophagocytic syndrome.
      Elevated PCT levels in SLE patients should always prompt a thorough search for
      sources of potential infection.

PMID- 25064127
TI  - Regulation of the hepatitis C virus RNA replicase by endogenous lipid
      peroxidation.
AB  - Oxidative tissue injury often accompanies viral infection, yet there is little
      understanding of how it influences virus replication. We show that multiple
      hepatitis C virus (HCV) genotypes are exquisitely sensitive to oxidative membrane
      damage, a property distinguishing them from other pathogenic RNA viruses. Lipid
      peroxidation, regulated in part through sphingosine kinase-2, severely restricts
      HCV replication in Huh-7 cells and primary human hepatoblasts. Endogenous
      oxidative membrane damage lowers the 50% effective concentration of direct-acting
      antivirals in vitro, suggesting critical regulation of the conformation of the
      NS3-4A protease and the NS5B polymerase, membrane-bound HCV replicase components.
      Resistance to lipid peroxidation maps genetically to transmembrane and membrane
      proximal residues within these proteins and is essential for robust replication
      in cell culture, as exemplified by the atypical JFH1 strain of HCV. Thus, the
      typical, wild-type HCV replicase is uniquely regulated by lipid peroxidation,
      providing a mechanism for attenuating replication in stressed tissue and possibly
      facilitating long-term viral persistence. 

PMID- 25064128
TI  - An epithelial circadian clock controls pulmonary inflammation and glucocorticoid
      action.
AB  - The circadian system is an important regulator of immune function. Human
      inflammatory lung diseases frequently show time-of-day variation in symptom
      severity and lung function, but the mechanisms and cell types underlying these
      effects remain unclear. We show that pulmonary antibacterial responses are
      modulated by a circadian clock within epithelial club (Clara) cells. These drive
      circadian neutrophil recruitment to the lung via the chemokine CXCL5. Genetic
      ablation of the clock gene Bmal1 (also called Arntl or MOP3) in bronchiolar cells
      disrupts rhythmic Cxcl5 expression, resulting in exaggerated inflammatory
      responses to lipopolysaccharide and an impaired host response to Streptococcus
      pneumoniae infection. Adrenalectomy blocks rhythmic inflammatory responses and
      the circadian regulation of CXCL5, suggesting a key role for the adrenal axis in
      driving CXCL5 expression and pulmonary neutrophil recruitment. Glucocorticoid
      receptor occupancy at the Cxcl5 locus shows circadian oscillations, but this is
      disrupted in mice with bronchiole-specific ablation of Bmal1, leading to enhanced
      CXCL5 expression despite normal corticosteroid secretion. The therapeutic effects
      of the synthetic glucocorticoid dexamethasone depend on intact clock function in
      the airway. We now define a regulatory mechanism that links the circadian clock
      and glucocorticoid hormones to control both time-of-day variation and the
      magnitude of pulmonary inflammation and responses to bacterial infection. 

PMID- 25064131
TI  - Effects of tumor necrosis factor-alpha on sexual activity of male patients with
      ankylosing spondylitis.
AB  - The objective of this study was to investigate the therapeutic effect of a tumor
      necrosis factor-alpha (TNF-alpha) antagonist on the sexual quality of life of
      male patients with ankylosing spondylitis (AS). In this open-label study, 42 AS
      patients were grouped into the TNF-alpha antagonist treatment group and the non
      TNF-alpha antagonist treatment group for 3 months. Clinical and laboratory
      indices and changes in the sexual quality of life were compared to assess the
      efficacy of TNF-alpha antagonists on sexual activity. The relationship between
      sexual quality and disease activity was analyzed. There were no significant
      differences in baseline data between the two groups. After treatment, disease
      activity and quality of life were improved in these two groups. The Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI) score (1.9 +/- 1.6 vs. 3.0
      +/- 1.3, p = 0.020), erythrocyte sedimentation rate (ESR) (9 +/- 7 mm/1 h vs. 18
      +/- 17 mm/1 h, p = 0.031), and C-reactive protein (CRP) levels (1.8 +/- 2.1 mg/dl
      vs. 6.2 +/- 8.5 mg/dl, p = 0.035) were significantly lower in the TNF-alpha
      antagonist treatment group than in the non-TNF-alpha antagonist treatment group.
      The extent of improvement in the quality of life was more evident in the TNF
      alpha antagonist treatment group. The average degree of improvement in the
      quality of life was negatively related to the BASDAI score and the Bath
      Ankylosing Spondylitis Functional Index score in the TNF-alpha antagonist
      treatment group (r = -0.497, p = 0.018; r = -0.558, p = 0.007, respectively).
      Sexual quality of life and disease activity are improved after treatment with TNF
      alpha antagonists in male patients with AS. The extent of improvement in sexual
      quality and disease activity are positively related. 

PMID- 25064132
TI  - A new alpha-galactosidase from thermoacidophilic Alicyclobacillus sp. A4 with
      wide acceptor specificity for transglycosylation.
AB  - An alpha-galactosidase gene (gal36A4) of glycosyl hydrolase family 36 was
      identified in the genome of Alicyclobacillus sp. A4. It contains an ORF of 2,187
      bp and encodes a polypeptide of 728 amino acids with a calculated molecular mass
      of 82.6 kDa. Deduced Gal36A4 shows the typical GH36 organization of three domains
      -the N-terminal beta-sheets, the catalytic (beta/alpha)8-barrels, and the C
      terminal antiparallel beta-sheet. The gene product was produced in Escherichia
      coli and showed both hydrolysis and transglycosylation activities. The optimal pH
      for hydrolysis activity was 6.0, and a stable pH range of 5.0-11.0 was found. The
      enzyme had a temperature optimum of 60  degrees C. It is specific for alpha-1,6
      glycosidic linkages and had a K m value of 1.45 mM toward pNPGal. When using
      melibiose as both donor and acceptor of galactose, Gal36A4 showed the transfer
      ratio of 23.25 % at 96 h. With respect to acceptor specificity, all tested
      monosaccharides, disaccharides, and oligosaccharides except for D-xylose and L
      arabinose were good acceptors for transglycosylation. Thus, Gal36A4 may find
      diverse applications in industrial fields, especially in the food industry.

PMID- 25064133
TI  - Toll-like receptor 22 in Labeo rohita: molecular cloning, characterization, 3D
      modeling, and expression analysis following ligands stimulation and bacterial
      infection.
AB  - Toll-like receptors (TLRs) are a class of innate immune receptors that sense
      pathogens or their molecular signatures and activate signaling cascades to induce
      a quick and non-specific immune response in the host. Among various types of
      TLRs, TLR22 is exclusively present in teleosts and amphibians and is expected to
      play the distinctive role in innate immunity. This report describes molecular
      cloning, three-dimensional (3D) modeling, and expression analysis of TLR22 in
      rohu (Labeo rohita), the most commercially important freshwater fish species in
      the Indian subcontinent. The open reading frame (ORF) of rohu TLR22 (LrTLR22)
      comprised of 2,838 nucleotides (nt), encoding 946 amino acid (aa) residues with
      the molecular mass of ~ 107.6 kDa. The secondary structure of deduced LrTLR22
      exhibited the presence of signal peptide (1-22 aa), 18 leucine-rich repeat (LRR)
      regions (79-736 aa), and TIR domain (792-935 aa). The 3D model of LrTLR22-LRR
      regions together elucidated the horse-shoe-shaped structure having parallel beta
      strands at the concave surface and few alpha-helices at the convex surface. The
      TIR domain structure revealed alternate presence of five alpha-helices and beta
      sheets. Phylogenetically, LrTLR22 was closely related to common carp and
      exhibited significant similarity (92.2 %) and identity (86.1 %) in their amino
      acids. In rohu, TLR22 was constitutively expressed in all embryonic developmental
      stages, and tissue-specific analysis illustrated its expression in all examined
      tissues, highest was in liver and lowest in brain. In vivo modulation of TLR22
      gene expression was analyzed by quantitative real-time PCR (qRT-PCR) assay
      following stimulation with lipopolysaccharide (LPS), synthetic double stranded
      RNA (polyinosinic-polycytidylic acid), and bacterial (Aeromonas hydrophila) RNA.
      Among these ligands, bacterial RNA most significantly (p < 0.05) induced TLR22
      gene expression in most of the tested tissues. In A. hydrophila infection,
      induction of TLR22 gene expression was also observed in majority of the tested
      tissues. Together, these data suggested that in addition to sensing other
      microbial signatures, TLR22 can recognize bacterial RNA and may play the
      important role in augmenting innate immunity in fish.

PMID- 25064134
TI  - Protein engineering of Bacillus thermocatenulatus lipase via deletion of the
      alpha5 helix.
AB  - Lipases from Bacillus thermocatenulatus are a member of superfamily of alpha/beta
      hydrolase, but there are structural differences between them. In this work, we
      focused on the alpha5 helix of B. thermocatenulatus lipase (BTL2) which is absent
      in canonical alpha/beta hydrolase fold. In silico study showed that the alpha5
      helix is a region that causes disorder in BTL2 protein. So, the alpha5 helix
      (residues 131 to 150) has been deleted from the B. thermocatenulatus lipase gene
      (BTL2) and the remain (Deltaalpha5-BTL2) has been expressed in Pichia pastoris
      yeast. The alpha5 deletion results in increase of enzyme-specific activity in the
      presence of tributyrin, tricaproin, tricaprylin, tricaprin, trilaurin, and olive
      oil (C18) substrates by 1.4-, 1.7-, 2.0-, 1.2-, 1.75-, and 1.95-fold,
      respectively. Also, deletion leads to increase in enzyme activity in different
      temperatures and pHs, whereas it did not significantly affect on enzyme activity
      in the presence of organic solvents, metal ions, and detergents.

PMID- 25064135
TI  - Treatment-related dysgeusia in head and neck cancer patients.
AB  - Head and neck cancer patients treated with radiotherapy and/or chemotherapy
      agents may develop altered taste acuity. This, together with radiation induced
      xerostomia and dysphagia, is a major contributory factor to the anorexia and
      concomitant morbidity often seen in this group of patients. This paper examines
      the existing literature in order to assess the prevalence of clinician and
      patient-reported dysgeusia in HNC patients undergoing oncological treatment. We
      also describe the temporal manifestations of the same and its reported impact on
      QOL. 

PMID- 25064137
TI  - [Response to the response of the authors (DOI: 10.1016 / j.neuchi.2014.05.001),
      following our "expert opinion" (DOI: 10.1016 / j.neuchi.2014.06.001)].

PMID- 25064136
TI  - Crystal structure of the lytic CHAP(K) domain of the endolysin LysK from
      Staphylococcus aureus bacteriophage K.
AB  - BACKGROUND: Bacteriophages encode endolysins to lyse their host cell and allow
      escape of their progeny. Endolysins are also active against Gram-positive
      bacteria when applied from the outside and are thus attractive anti-bacterial
      agents. LysK, an endolysin from staphylococcal phage K, contains an N-terminal
      cysteine-histidine dependent amido-hydrolase/peptidase domain (CHAP(K)), a
      central amidase domain and a C-terminal SH3b cell wall-binding domain. CHAP(K)
      cleaves bacterial peptidoglycan between the tetra-peptide stem and the penta
      glycine bridge. METHODS: The CHAP(K) domain of LysK was crystallized and high
      resolution diffraction data was collected both from a native protein crystal and
      a methylmercury chloride derivatized crystal. The anomalous signal contained in
      the derivative data allowed the location of heavy atom sites and phase
      determination. The resulting structures were completed, refined and analyzed. The
      presence of calcium and zinc ions in the structure was confirmed by X-ray
      fluorescence emission spectroscopy. Zymogram analysis was performed on the enzyme
      and selected site-directed mutants. RESULTS: The structure of CHAP(K) revealed a
      papain-like topology with a hydrophobic cleft, where the catalytic triad is
      located. Ordered buffer molecules present in this groove may mimic the
      peptidoglycan substrate. When compared to previously solved CHAP domains, CHAP(K)
      contains an additional lobe in its N-terminal domain, with a structural calcium
      ion, coordinated by residues Asp45, Asp47, Tyr49, His51 and Asp56. The presence
      of a zinc ion in the active site was also apparent, coordinated by the catalytic
      residue Cys54 and a possible substrate analogue. Site-directed mutagenesis was
      used to demonstrate that residues involved in calcium binding and of the proposed
      active site were important for enzyme activity. CONCLUSIONS: The high-resolution
      structure of the CHAP(K) domain of LysK was determined, suggesting the location
      of the active site, the substrate-binding groove and revealing the presence of a
      structurally important calcium ion. A zinc ion was found more loosely bound.
      Based on the structure, we propose a possible reaction mechanism. Future studies
      will be aimed at co-crystallizing CHAP(K) with substrate analogues and
      elucidating its role in the complete LysK protein. This, in turn, may lead to the
      design of site-directed mutants with altered activity or substrate specificity.

PMID- 25064139
TI  - Tonsillotomy versus tonsillectomy on young children: 2 year post surgery follow
      up.
AB  - ObjectivesTo study the long-term effect of tonsillotomy and tonsillectomy in
      young children after two years in comparison to the results after six
      months.MethodChildren, age 4-5 with Sleep Disordered Breathing (SDB) and tonsil
      hyperplasia, were randomized to TE (32) or TT (35). TT was performed ad modum
      Hultcrantz with radiofrequency technique (Ellman). An adenoidectomy with cold
      steel was performed in the same session for 80% of cases. The patients were
      assessed prior to surgery, at six and 24 months postoperatively. Effects of
      surgery were evaluated clinically, through questionnaire (general
      health/snoring/ENT-infections), Quality of Life (QoL), survey of pediatric
      obstructive sleep apnea with OSA-18, and children?s behavior with the Child
      Behavior Checklist.ResultsAfter two years there was still no difference between
      the groups with respect to snoring and frequency or severity of upper airway
      infections. Both TT and TE had resulted in large improvement in short and long
      term QoL and behavior. Three TT-children and one TE child had been re-operated
      due to recurrence of obstructive problems, the TE-child and one of the TT
      children with adenoidectomy and two of the TT-children with tonsillectomy. Three
      of the TT-children had tonsil tissue protruding slightly out of the tonsil pouch
      and twelve TE-children had small tonsil remnants within the tonsil pouches, but
      with no need for surgery.ConclusionYounger children have a small risk of symptom
      recurrence requiring re-surgery within two years after TT. For the majority, the
      positive effect on snoring, infections, behavior and quality of life remain and
      is similar to TE.

PMID- 25064138
TI  - High progesterone levels in women with high ovarian response do not affect
      clinical outcomes: a retrospective cohort study.
AB  - BACKGROUND: The potentially detrimental role of progesterone during the
      follicular phase has been a matter of controversy for several years; however, few
      studies have analyzed the effects of combined raised estradiol and progesterone
      levels on pregnancy outcomes. The aim of the present study was to determine the
      influence of high progesterone levels on clinical outcomes in the context of high
      ovarian response. METHODS: We performed a retrospective cohort study that
      included 2850 women classified as high responders. The women were subdivided into
      six groups depending on their progesterone concentration on the day of human
      chorionic gonadotropin (hCG) administration: <0.5 ng/ml (<p10), 0.50-0.70 ng/ml
      (p10-p25), 0.71-1.00 ng/ml (p25-p50), 1.01-1.40 ng/ml (p50-p75), 1.41-1.80 ng/ml
      (p75-p90) and >1.81 ng/ml (>p90). Ovarian response was classified as high
      when>=20 oocytes were retrieved or when estradiol was >=3000 pg/ml. Clinical
      outcomes of each subgroup were analyzed. We also examined data from frozen-thawed
      embryo transfers. Results were analyzed with Student's t- test to compare
      continuous variables and chi-squared test to compare proportions. A p-value of<
      =0.05 was considered statistically significant. RESULTS: The progesterone
      concentration increased with ovarian response, and elevated progesterone did not
      show a significant clinical impact on implantation rate and pregnancy rates.
      These data provide evidence that progesterone levels higher than 1.8 ng/ml do not
      have detrimental effect on oocyte quality or endometrial receptivity.
      CONCLUSIONS: These data allow us to conclude that high progesterone levels
      correlate significantly with high estradiol levels and that in high responder
      women; progesterone levels do not show a significant clinical impact on results.

PMID- 25064140
TI  - Effects of triclosan on the detoxification system in the yellow catfish
      (Pelteobagrus fulvidraco): expressions of CYP and GST genes and corresponding
      enzyme activity in phase I, II and antioxidant system.
AB  - Triclosan (TCS), a broad-spectrum antibacterial agent widely used in
      pharmaceuticals and personal case products (PPCPs), has been universally detected
      in aquatic ecosystem in recent years. Unfortunately, there is limited information
      about its potential impacts on responses of genes and enzymes related to fish
      detoxification. In the present work, we cloned CYP3A and alpha-GST of yellow
      catfish (Pelteobagrus fulvidraco) and tested the transcriptional expression of
      CYP1A, CYP3A and GST as well as the alterations of their corresponding enzymes,
      including ethoxyresorufin-O-deethylase (EROD), aminopyrine N-demethylase (APND),
      erythromycin N-demethylase (ERND), glutathione S-transferase (GST) and catalase
      (CAT), and also the oxidative product malondialdehyde (MDA) content in the liver
      of P. fulvidraco exposed to TCS. Amino acids of CYP3A and GST were deduced and
      phylogenetic tree was constructed respectively. High identity percent was
      exhibited between P. fulvidraco and other species, such as other fish, birds and
      mammals. Results indicated that TCS significantly elevated CYP1A and GST but
      decreased CYP3A expression, EROD activity and MDA content at lower concentrations
      of TCS at 24h. Moreover, CYP3A and GST were significantly inhibited at 72 h but
      induced at 168 h at lower concentrations. However, CYP3A was always induced at
      the highest concentration during the exposure period. Furthermore, CYP3A, GST,
      GST enzyme and MDA content exhibited a dose-effect relationship to some extent,
      but no significant responses were observed in ERND, APND and CAT except for
      individual treatments. Taken together, EROD was the most sensitive to TCS
      exposure as compared to other enzymes. Meanwhile, mRNA responses were more
      sensitive in yellow catfish.

PMID- 25064141
TI  - Accumulation of heme oxygenase-1 (HSP32) in Xenopus laevis A6 kidney epithelial
      cells treated with sodium arsenite, cadmium chloride or proteasomal inhibitors.
AB  - The present study examined the effect of sodium arsenite, cadmium chloride, heat
      shock and the proteasomal inhibitors MG132, withaferin A and celastrol on heme
      oxygenase-1 (HO-1; also known as HSP32) accumulation in Xenopus laevis A6 kidney
      epithelial cells. Immunoblot analysis revealed that HO-1 accumulation was not
      induced by heat shock but was enhanced by sodium arsenite and cadmium chloride in
      a dose- and time-dependent fashion. Immunocytochemistry revealed that these
      metals induced HO-1 accumulation in a granular pattern primarily in the
      cytoplasm. Additionally, in 20% of the cells arsenite induced the formation of
      large HO-1-containing perinuclear structures. In cells recovering from sodium
      arsenite or cadmium chloride treatment, HO-1 accumulation initially increased to
      a maximum at 12h followed by a 50% reduction at 48 h. This initial increase in HO
      1 levels was likely the result of new synthesis as it was inhibited by
      cycloheximide. Interestingly, treatment of cells with a mild heat shock enhanced
      HO-1 accumulation induced by low concentrations of sodium arsenite and cadmium
      chloride. Finally, we determined that HO-1 accumulation was induced in A6 cells
      by the proteasomal inhibitors, MG132, withaferin A and celastrol. An examination
      of heavy metal and proteasomal inhibitor-induced HO-1 accumulation in amphibians
      is of importance given the presence of toxic heavy metals in aquatic habitats.

PMID- 25064142
TI  - Purple glove syndrome occurring after oral administration of phenytoin in
      therapeutic doses: mechanism still a dilemma.
AB  - Purple glove syndrome is a rare and poorly understood complication of phenytoin
      use, occurring almost always with its intravenous formulation. This syndrome
      comprises of pain, purple discoloration, and edema distal to the site of
      intravenous administration of phenytoin. We hereby report an unusual case,
      wherein purple glove syndrome was seen on oral formulation of phenytoin in its
      therapeutic dose.

PMID- 25064143
TI  - Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent
      protein kinase II in resting sensory neurons.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key
      element in encoding depolarization activity of excitable cells into facilitated
      voltage-gated Ca(2+) channel (VGCC) function. Less is known about the
      participation of CaMKII in regulating VGCCs in resting cells. We examined
      constitutive CaMKII control of Ca(2+) currents in peripheral sensory neurons
      acutely isolated from dorsal root ganglia (DRGs) of adult rats. The small
      molecule CaMKII inhibitor KN-93 (1.0MUM) reduced depolarization-induced ICa by 16
      30% in excess of the effects produced by the inactive homolog KN-92. The
      specificity of CaMKII inhibition on VGCC function was shown by the efficacy of
      the selective CaMKII blocking peptide autocamtide-2-related inhibitory peptide in
      a membrane-permeable myristoylated form, which also reduced VGCC current in
      resting neurons. Loss of VGCC currents is primarily due to reduced N-type
      current, as application of mAIP selectively reduced N-type current by
      approximately 30%, and prior N-type current inhibition eliminated the effect of
      mAIP on VGCCs, while prior block of L-type channels did not reduce the effect of
      mAIP on total ICa. T-type currents were not affected by mAIP in resting DRG
      neurons. Transduction of sensory neurons in vivo by DRG injection of an adeno
      associated virus expressing AIP also resulted in a loss of N-type currents.
      Together, these findings reveal a novel molecular adaptation whereby sensory
      neurons retain CaMKII support of VGCCs despite remaining quiescent.

PMID- 25064144
TI  - Distinct modulation of the endocannabinoid system upon kainic acid-induced in
      vivo seizures and in vitro epileptiform bursting.
AB  - There is clear evidence on the neuroprotective role of the endocannabinoid (eCB)
      signaling cascade in various models of epilepsy. In particular, increased levels
      of eCBs protect against kainic acid (KA)-induced seizures. However, the molecular
      mechanisms underlying this effect and its age-dependence are still unknown. To
      clarify this issue, we investigated which step of the biosynthetic and catabolic
      pathways of the eCBs may be responsible for the eCB-mediated neuroprotection in
      the hippocampus of P14 and P56-70 KA-treated rats. We found that both anandamide
      and N-palmitoylethanolamine, together with their biosynthetic enzyme
      significantly increased in the hippocampus of younger KA-treated rats, while
      decreasing in adults. In contrast, the levels of the other major eCB, 2
      arachidonoylglycerol, similar to its biosynthetic enzyme, were higher in the
      hippocampus of P56-70 compared to P14 rats. In line with these data,
      extracellular field recordings in CA1 hippocampus showed that enhancement of
      endogenous AEA and 2-AG significantly counteracted KA-induced epileptiform
      bursting in P56-70 and P14 rats, respectively. On the contrary, while the CB1R
      antagonist SR141716 per se did not affect the population spike, it did worsen KA
      induced bursts, confirming increased eCB tone upon KA treatment. Altogether these
      data indicate an age-specific alteration of the eCB system caused by KA and
      provide insights for the protective mechanism of the cannabinoid system against
      epileptiform discharges.

PMID- 25064145
TI  - Applications of nuclear reprogramming and directed differentiation in vascular
      regenerative medicine.
AB  - As vertebrates proceed through embryonic development the growing organism cannot
      survive on diffusion of oxygen and nutrients alone and establishment of vascular
      system is fundamental for embryonic development to proceed. Dysfunction of the
      vascular system in adults is at the heart of many disease states such as
      hypertension and atherosclerosis. In this review we will focus on attempts to
      generate the key cells of the vascular system, the endothelial and smooth muscle
      cells, using human embryonic stem cells (hESCs) and human induced pluripotent
      stem cells (iPSCs). Regardless of their origin, be it embryonic or via somatic
      cell reprogramming, pluripotent stem cells provide limitlessly self-renewing
      populations of material suitable for the generation of multi-lineage isogenic
      vascular cells-types that can be used as tools to study normal cell and tissue
      biology, model disease states and also as tools for drug screening and future
      cell therapies. 

PMID- 25064146
TI  - The reliability of site determination methods in ventrogluteal area injection: a
      cross-sectional study.
AB  - BACKGROUND: While administering medication through intramuscular injection, the
      ventrogluteal site must be used instead of the dorsogluteal site, and it is of
      great significance to locate the ventrogluteal site correctly. OBJECTIVE: To
      determine the reliability of two different methods used to determine the
      ventrogluteal site in intramuscular injection practice. DESIGN: A cross-sectional
      study. SETTINGS: A university hospital in Istanbul. PARTICIPANTS: The study
      population comprised 120 randomly selected healthcare personnel at a university
      hospital. METHODS: The ventrogluteal site was determined using the geometric (G
      method) and V method and these sites were scrutinized under ultrasonography. It
      was investigated whether there was any anatomic vessels or neural structure
      present, and also determined the thickness of subcutaneous tissue, musculus
      gluteus medius, and musculus gluteus minimus. RESULTS: Of the participants, 65.8%
      were female and the average age was 32.30 years and body mass index was 25.31
      kg/m(2). The results showed that G and V methods were statistically significant
      in terms of variables. It was also found that sex affects subcutaneous tissue
      thickness and the skin-bone margin in the G and V method, and that body mass
      index determines subcutaneous tissue, musculus gluteus medius thickness and skin
      bone margin. CONCLUSION: When the ventrogluteal site is used for intramuscular
      injection purposes, the site must be determined in line with the geometric
      method.

PMID- 25064147
TI  - Relationships between pain misconceptions, disability, patients' goals and
      interpretation of information from hand therapists.
AB  - INTRODUCTION: Patient interpretation of advice from hand therapists may be
      related to nonadaptive pain thoughts (automatic, overprotective, unduly
      pessimistic statements triggered by nociception and exacerbated by psychological
      distress). PURPOSE OF THE STUDY: This study aimed to determine whether there were
      correlations between participants' hand therapy goals, interpretation of advice
      from hand therapists, nonadaptive pain thoughts, and upper extremity-specific
      disability. METHODS: One hundred and five participants completed questionnaires
      assessing nonadaptive pain thoughts, upper extremity-specific disability, lessons
      from hand therapists, and hand therapy goals. RESULTS: Nonadaptive pain thoughts
      correlated with disability and were bi-directionally related to participant goals
      and interpretation of advice from hand therapists. DISCUSSION: Patients'
      nonadapative pain thoughts and the words/concepts used by hand therapists are
      both important in recovery from upper extremity illness. CONCLUSIONS: Hand
      therapists should be mindful that nonadaptive pain thoughts are an important
      determinant of disability and that such thoughts can affect and be affected by
      their recommendations. LEVEL OF EVIDENCE: n/a.

PMID- 25064148
TI  - Innovations in diagnosis and post-therapeutic monitoring of Chagas disease:
      Simultaneous flow cytometric detection of IgG1 antibodies anti-live amastigote,
      anti-live trypomastigote, and anti-fixed epimastigote forms of Trypanosoma cruzi.
AB  - This study developed a remarkable methodological innovation (FC-ATE) which
      enables simultaneous detection of antibodies specific to the three evolutive
      forms of Trypanosoma cruzi: live amastigote (AMA), live trypomastigote (TRYPO),
      and fixed epimastigote (EPI) using a differential fluorescence staining as low
      (AMA), intermediate (TRYPO), and high (EPI). An outstanding performance (100%)
      was observed in the discrimination of the chagasic (CH) and non-chagasic (NCH)
      patients. In the applicability of FC-ATE in the diagnosis of Chagas disease, 100%
      of the CH samples presented positivity in the percentage of positive fluorescent
      parasites (PPFP) for all the three forms of T. cruzi. Moreover, 94% of the
      samples of NCH presented negative values of PPFP with AMA and TRYPO, and 88% with
      EPI. Samples from the NCH group with false-positive results were those belonging
      to the leishmaniasis patients. Considering the applicability of this technique in
      post-therapeutic monitoring of Chagas disease, 100% of non-treated (NT) and
      treated non-cured (TNC) samples were positive with the three T. cruzi evolutive
      forms, while a percentage of 100% from samples of the treated cured (TC) patients
      were negative with AMA, 93% with TRYPO and 96% with EPI. The comparison between
      FC-ATE and two other flow cytometric tests using the same samples of patients NT,
      TNC and TC showed that the three techniques presented different reactivities,
      although categorical correlation between the methodologies was observed. Taken
      together, the results obtained with the novel FC-ATE method have shown an
      outstanding performance in the diagnosis and post-therapeutic monitoring of
      Chagas disease. 

PMID- 25064149
TI  - Calcium-sensitive immunoaffinity chromatography: Gentle and highly specific
      retrieval of a scarce plasma antigen, collectin-LK (CL-LK).
AB  - Immunoaffinity chromatography is a powerful fractionation technique that has
      become indispensable for protein purification and characterization. However, it
      is difficult to retrieve bound proteins without using harsh or denaturing elution
      conditions, and the purification of scarce antigens to homogeneity may be
      impossible due to contamination with abundant antigens. In this study, we
      purified the scarce, complement-associated plasma protein complex, collectin LK
      (CL-LK, complex of collectin liver 1 and kidney 1), by immunoaffinity
      chromatography using a calcium-sensitive anti-collectin-kidney-1 mAb. This
      antibody was characterized by binding to CL-LK at hypo- and physiological calcium
      concentrations and dissociated from CK-LK at hyperphysiological concentrations of
      calcium. We purified CL-LK from plasma to a purity of 41% and a yield of 38%,
      resulting in a purification factor of more than 88,000 in a single step. To
      evaluate the efficiency of this new purification scheme, we purified CL-LK using
      the same calcium-sensitive mAb in combination with acidic elution buffer and by
      using calcium-dependent anti-CL-K1 mAbs in combination with EDTA elution buffer.
      We found that calcium-sensitive immunoaffinity chromatography was superior to the
      traditional immunoaffinity chromatographies and resulted in a nine-fold
      improvement of the purification factor. The technique is applicable for the
      purification of proteins in complex mixtures by single-step fractionation without
      the denaturation of eluted antigens, and it allows for the purification of scarce
      proteins that would have otherwise been impossible to purify and, hence, to
      characterize. This technique may also potentially be applied for the purification
      of proteins that only interact with calcium ions at hyperphysiological
      concentrations. 

PMID- 25064150
TI  - Interspinous spacer decompression (X-STOP) for lumbar spinal stenosis and
      degenerative disk disease: a multicenter study with a minimum 3-year follow-up.
AB  - Interspinous distraction devices provide an effective treatment for patients
      suffering from lumbar spinal stenosis and/or degenerative disk disease. The aim
      of this multicenter study was the prospective evaluation of patients treated for
      symptomatic lumbar spinal stenosis with interspinous process decompression (IPD)
      implants compared with a population of patients managed with conservative
      treatment. 542 patients affected by symptomatic lumbar spine degenerative disease
      were enrolled in a controlled trial. 422 patients underwent surgical treatment
      consisting of X-STOP device implantation, whereas 120 control cases were managed
      conservatively. Both patient groups underwent follow-up evaluations at 6, 12, 24,
      and 36 months using the Zurich Claudication Questionnaire, the Visual Analog
      Scale score and spinal lumbar X-rays, CT scans and MR imaging. One-year follow-up
      evaluation revealed positive good results in the 83.5% of patients treated with
      IPD with respect to 50% of the nonoperative group cases. During the first three
      years, in 38 out of the 120 control cases, a posterior decompression and/or
      spinal fixation was performed because of unsatisfactory results of the
      conservative therapy. In 24 of 422 patients, the IPD device had to be removed,
      and a decompression and/or pedicle screw fixation was performed because of the
      worsening of neurological symptoms. Our results support the effectiveness of
      surgery in patients with stenosis. IPD may offer an effective and less invasive
      alternative to classical microsurgical posterior decompression in selected
      patients with spinal stenosis and lumbar degenerative disk diseases. 

PMID- 25064151
TI  - Glioblastoma multiforme in the brainstem in a young adult.

PMID- 25064152
TI  - Cerebral phaeohyphomycosis in an immunocompetent patient: a case report and
      literature summary.

PMID- 25064153
TI  - Reliability of the Japanese version of the scales for outcomes in Parkinson's
      disease-autonomic questionnaire.
AB  - OBJECTIVE: The Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT)
      questionnaire was used to assess autonomic dysfunction in patients with
      neurological disorders. The aim of this study was to evaluate the reliability of
      the Japanese version of the SCOPA-AUT. METHODS: We translated the SCOPA-AUT from
      English to Japanese. Thirty-one patients with diseases involving autonomic
      symptoms completed the form twice. The reliability was assessed by Cronbach's
      coefficient alphas and intraclass correlation coefficients (ICCs). RESULTS: The
      average (standard deviation, SD) total scores of the first and second assessments
      of the SCOPA-AUT were 15.7 (SD, 7.1) and 13.6 (SD, 6.5), respectively. The
      Cronbach's coefficient alphas were globally high, but the ICCs were moderately
      high. The valid response rates for the questions about sexual dysfunction were
      36.7% in men and 26.6% in women. CONCLUSIONS: The Japanese version of the SCOPA
      AUT had high internal consistency. However, the questions about sexual
      dysfunction showed less valid response rates.

PMID- 25064154
TI  - Sacral dural arteriovenous fistula presented as an acute isolated thoracic
      myelopathy: clinical and surgical importance.
AB  - We report a case of dural Arteriovenous Fistula (AVF) supplied by the lateral
      sacral artery that is located in the sacral region and presented as isolated
      thoracic myelopathy. METHOD AND RESULTS: After S3 hemilaminectomy and opening the
      dura, the engorged arterialized vein has been interrupted. Postoperatively, the
      patient's symptoms and myelopathy gradually resolved. CONCLUSION: We are going to
      highlight the clinical and surgical importance of our case and discuss the
      pathophysiology of such an unusual clinical finding.

PMID- 25064155
TI  - Three dimensional (temperature-tension-composition) phase map of mixed DOPC-DPPC
      vesicles: Two solid phases and a fluid phase coexist on three intersecting
      planes.
AB  - Mapping the phase behavior of multicomponent phospholipid membranes has been an
      ongoing pursuit, motivated by interest in both fundamental physics and cell
      function. Prior investigations addressed temperature-composition space and the
      features of the associated domains. The current study additionally considers
      membrane tension, analogous to pressure in bulk materials. Focusing on model
      mixed 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DOPC and DPPC respectively) membranes, we examine the
      thermodynamic impact of tension on fluid-solid coexistence and the nature of
      phase-separated domains. Reported here is the 3 dimensional composition
      temperature-tension phase map containing three intersecting curved surfaces.
      Depending on the system's position in this 3D space, giant unilamellar vesicles
      containing DOPC and DPPC may exhibit, in addition to a 2-component fluid Lalpha
      phase, two different types of solid DPPC-rich domains: tracer-excluding hexagonal
      patches or tracer-selective stripes. The fluid phase occurs at high temperatures.
      At cool temperatures striped solid DPPC-rich domains coexist with the fluid at
      elevated tensions. These stripes occur independent of tension, at the coolest
      temperatures. At low tensions and intermediate temperatures, patchy solid DPPC
      rich domains coexist with the Lalpha fluid and may persist, if kinetically
      trapped, at lower temperatures. We associate the striped DPPC domains with a tilt
      gel (Lbeta') morphology and the hexagonal DPPC patches with a dense corrugated
      ripple phase (Pbeta'). These assignments, based on the reported areal densities
      of the corrugated and tilt solids, enabled first principles estimates of the
      coexistence boundaries that match the experiments well, including the tension
      sensitivity of coexistence curves and triple-point-like features for fixed
      composition. 

PMID- 25064156
TI  - Improving the apo-state detergent stability of NTS1 with CHESS for
      pharmacological and structural studies.
AB  - The largest single class of drug targets is the G protein-coupled receptor (GPCR)
      family. Modern high-throughput methods for drug discovery require working with
      pure protein, but this has been a challenge for GPCRs, and thus the success of
      screening campaigns targeting soluble, catalytic protein domains has not yet been
      realized for GPCRs. Therefore, most GPCR drug screening has been cell-based,
      whereas the strategy of choice for drug discovery against soluble proteins is HTS
      using purified proteins coupled to structure-based drug design. While recent
      developments are increasing the chances of obtaining GPCR crystal structures, the
      feasibility of screening directly against purified GPCRs in the unbound state
      (apo-state) remains low. GPCRs exhibit low stability in detergent micelles,
      especially in the apo-state, over the time periods required for performing large
      screens. Recent methods for generating detergent-stable GPCRs, however, offer the
      potential for researchers to manipulate GPCRs almost like soluble enzymes,
      opening up new avenues for drug discovery. Here we apply cellular high-throughput
      encapsulation, solubilization and screening (CHESS) to the neurotensin receptor 1
      (NTS1) to generate a variant that is stable in the apo-state when solubilized in
      detergents. This high stability facilitated the crystal structure determination
      of this receptor and also allowed us to probe the pharmacology of detergent
      solubilized, apo-state NTS1 using robotic ligand binding assays. NTS1 is a target
      for the development of novel antipsychotics, and thus CHESS-stabilized receptors
      represent exciting tools for drug discovery. 

PMID- 25064157
TI  - Reply to letter "Remarks on cerebral infarct from another point of view".

PMID- 25064158
TI  - Low-temperature biosynthesis of fluorescent semiconductor nanoparticles (CdS) by
      oxidative stress resistant Antarctic bacteria.
AB  - Bacterial biosynthesis of nanoparticles represents a green alternative for the
      production of nanostructures with novel properties. Recently, the importance of
      antioxidant molecules on the biosynthesis of semiconductor fluorescent
      nanoparticles (quantum dots, QDs) by mesophilic bacteria was reported. The
      objective of this work was the isolation of psychrotolerant, oxidative stress
      resistant bacteria from Antarctica to determine their ability for biosynthesizing
      CdS QDs at low temperatures. QDs biosynthesis at 15  degrees C was evaluated by
      determining their spectroscopic properties after exposing oxidative-stress
      resistant isolates identified as Pseudomonas spp. to Cd(2+) salts. To
      characterize the QDs biosynthetic process, the effect of metal exposure on
      bacterial fluorescence was determined at different times. Time-dependent changes
      in fluorescence color (green to red), characteristic of QDs, were observed.
      Electron microscopy analysis of fluorescent cells revealed that biosynthesized
      nanometric structures localize at the cell periphery. QDs were purified from the
      bacterial isolates and their fluorescence properties were characterized. Emission
      spectra displayed classical CdS peaks when excited with UV light. Thiol content,
      peroxidase activity, lipopolysaccharide synthesis, metabolic profiles and sulfide
      generation were determined in QDs-producing isolates. No relationship between QDs
      production and cellular thiol content or peroxidase activity was found. However,
      sulfide production enhanced CdS QDs biosynthesis. In this work, the use of
      Antarctic psychrotolerant Pseudomonas spp. for QDs biosynthesis at low
      temperature is reported for the first time.

PMID- 25064159
TI  - Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and
      AP-1 inhibition and heme oxygenase-1 induction in astrocytes.
AB  - HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related
      encephalitis and dementia. Celastrol possesses various biological activities such
      as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we
      investigated the modulatory effects of celastrol on HIV-1 Tat-induced
      inflammatory responses and the molecular mechanisms underlying its action in
      astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol
      significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and
      subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol
      suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as
      CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK
      MAPK, AP-1, and NF-kappaB. Furthermore, celastrol induced mRNA and protein
      expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using
      siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced
      inflammatory responses. These results suggest that celastrol has regulatory
      effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP
      1/NF-kappaB signaling pathways and inducing HO-1 expression in astrocytes. 

PMID- 25064161
TI  - An effective procedure to create a speckle pattern on biological soft tissue for
      digital image correlation measurements.
AB  - Creating a speckle pattern on biological soft tissue, which would be suitable for
      digital image correlation measurements, is challenging. Speckle patterns should
      neither cause or require sample dehydration, nor alter the mechanical response,
      but they should adhere to the tissue surface and withstand large deformations. A
      two-step procedure has been implemented to create a highly-contrasted pattern. It
      requires staining of the tissue with methylene blue solution to obtain a dark
      background and airbrushing the surface with paint to create white speckles. This
      study evaluated the effectiveness of the proposed procedure and whether the
      pattern creation had any effect on the elastic response of soft tissue. Forty
      porcine collateral ligaments underwent three series of cyclic tensile tests to a
      nominal elongation of 10% for 30 cycles. The specimen stiffness was calculated
      from the load-elongation curve collected during the last 10 cycles. One side of
      20 ligaments was blue stained between the first and second test series, and white
      patterned between the second and third test series. During the last series,
      ligament surface images were also acquired and elaborated using the digital image
      correlation technique. The other 20 ligaments were untreated. The data show a
      small non-significant upward trend in stiffness in treated as well as in
      untreated ligaments (maximum increase of 1.7%). The 'successfully-correlated
      area' of the stereo-visible ligament surface was on average 96%, i.e. small parts
      of the 'stereo-visible area' were lost during computation. The described
      procedure is an effective method to create a pattern on biological soft tissues. 

PMID- 25064160
TI  - Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS
      driven DNA damage and apoptosis.
AB  - Dietary phytochemicals are excellent ROS-modulating agents and have been shown to
      effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure
      their selective killing while leaving normal cells unscathed. Here we demonstrate
      that hydroxychavicol (HC), extracted and purified from Piper betel leaves,
      significantly inhibits growth and proliferation via ROS generation in human
      prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression,
      reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading
      to activation of several pro-apoptotic molecules. In addition, HC treatment
      elicited a novel autophagic response as evidenced by the appearance of acidic
      vesicular organelles and increased expression of autophagic markers, LC3-IIb and
      beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered
      significant protection against HC-induced inhibition of cell growth and down
      regulation of caspase-3, suggesting the crucial role of ROS in mediating cell
      death. The collapse of mitochondrial transmembrane potential by HC further
      revealed the link between ROS generation and induction of caspase-mediated
      apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor
      xenografts by ~72% upon daily oral administration of 150mg/kg bw HC by
      quantitative tumor volume measurements and non-invasive real-time bioluminescent
      imaging. HC was well-tolerated at this dosing level without any observable
      toxicity. This is the first report to demonstrate the anti-prostate cancer
      efficacy of HC in vitro and in vivo, which is perhaps attributable to its
      selective prooxidant activity to eliminate cancer cells thus providing compelling
      grounds for future preclinical studies to validate its potential usefulness for
      prostate cancer management. 

PMID- 25064162
TI  - Resource utilization and outcomes of infective endocarditis in children.
AB  - OBJECTIVE: To evaluate resource use and outcomes of infective endocarditis in
      children with and without preexisting heart disease via a national cohort. STUDY
      DESIGN: Children <19 years of age hospitalized from 2004 to 2010 with infective
      endocarditis at 37 centers in the Pediatric Health Information Systems database
      were included. We excluded children primarily hospitalized for chronic medical
      conditions. We used regression analysis to evaluate factors associated with poor
      outcomes (defined as mortality, mechanical cardiac support, or stroke). RESULTS:
      There were 1033 cases of infective endocarditis, of which 663 had heart disease
      and 370 did not. Compared with the group without heart disease, infective
      endocarditis in the cohort with heart disease occurred at younger age, was more
      commonly attributable to streptococcus, was more likely to require cardiac
      surgery for infective endocarditis, and was associated with a lower risk of
      stroke. Mortality was 6.7% (n = 45) and 3.5% (n = 13) in groups with and without
      heart disease, respectively. Factors associated with poor outcome in the cohort
      with heart disease included greater risk of mortality score (OR 7.9), mechanical
      ventilation (OR 3.1), use of antiarrhythmics (OR 2.7), and use of vasoactive
      medications (OR 3.8). In the cohort without heart disease, factors associated
      with poor outcome included renal failure (OR 19.3), greater risk of mortality
      score (OR 4.2), use of antiarrhythmics (OR 3.8), and mechanical ventilation (OR
      2.2). Median charge of hospitalization was $131,893 in the group without heart
      disease and $140,655 in the group with heart disease. CONCLUSION: Infective
      endocarditis remains a significant cause of morbidity, mortality, and resource
      use particularly in children with heart disease.

PMID- 25064163
TI  - Development of a new risk score for hospital-associated venous thromboembolism in
      noncritically ill children: findings from a large single-institutional case
      control study.
AB  - OBJECTIVE: To determine risk factors for pediatric hospital-associated venous
      thromboembolism (HA-VTE) in noncritically ill children to derive a novel HA-VTE
      risk model for this population. STUDY DESIGN: Patients with HA-VTE were
      identified retrospectively via the electronic health record at All Children's
      Hospital Johns Hopkins Medicine from April 10, 2013 through January 1, 2006.
      Seven contemporaneous, noncritically ill control children were randomly selected
      for each case of HA-VTE. The association between putative risk factors and HA-VTE
      was estimated with ORs and 95% CIs, which were calculated using the Wald method.
      A P-value threshold <=.2 was used in univariate analysis for inclusion into a
      multivariate (adjusted) model. RESULTS: Fifty cases of HA-VTE occurred in
      noncritically ill children. The presence of a central venous catheter (OR 27.67,
      95% CI, 8.40-91.22), infection (OR 10.40, 95% CI, 3.46-31.25), and length of stay
      >=4 days (OR 5.26, 95% CI, 1.74-15.88) were found to be statistically significant
      risk factors for HA-VTE. An 8-point risk score was derived in which scores of 8
      points, 7 points, and <=6 points corresponded to venous thromboembolism risks of
      12.5%, 1.1%, and 0.1%, respectively. CONCLUSION: The presence of a central venous
      catheter, infection, and length of stay >=4 days are significant risk factors for
      HA-VTE in noncritically ill children, forming the basis for a new risk score that
      could inform venous thromboembolism prophylaxis decision-making. These findings
      warrant prospective validation.

PMID- 25064165
TI  - The effect of monitor design and implementation on patient management.

PMID- 25064164
TI  - Antenatal pharmacokinetics and placental transfer of N-acetylcysteine in
      chorioamnionitis for fetal neuroprotection.
AB  - OBJECTIVE: To determine the pharmacokinetics (PK) and placental transfer of
      intravenous (i.v.) N-acetylcysteine (NAC) in mothers with a clinical diagnosis of
      chorioamnionitis (CA) and determine the PK of i.v. NAC in their infants. STUDY
      DESIGN: In this prospective, double-blind study i.v. NAC 100 mg/kg/dose or saline
      was administered within 4 hours of CA diagnosis to pregnant women >=24 weeks'
      gestation and then every 6 hours until delivery. Maternal PK and placental
      transfer were determined with maternal blood and matched maternal and cord venous
      blood. Neonatal PK estimates were determined from i.v. NAC (12.5-25 mg/kg/dose)
      administered every 12 hours for 5 doses. Noncompartmental analyses were performed
      for maternal and neonatal PK estimates. RESULTS: Eleven mothers (5 preterm, 6
      near-term) and 12 infants (1 set of twins) received NAC. Maternal clearance (CL)
      of NAC was faster than in nonpregnant adults, with a terminal elimination half
      life of 1.2 +/- 0.2 hours. The NAC cord to maternal ratio was 1.4 +/- 0.8,
      suggesting rapid placental transfer and slower rate of fetal CL. Neonatal PK
      estimates for near-term compared with preterm infants showed a significantly
      shorter terminal elimination half-life (5.1 vs 7.5 hours, respectively) and
      greater CL (53.7 vs 45.0 mL/h/kg, respectively). CONCLUSIONS: Maternal CL and
      placental transfer of NAC was rapid, with umbilical cord concentrations
      frequently exceeding maternal concentrations. The administration of NAC to
      mothers with CA achieves predictable NAC plasma concentrations in the fetus,
      indicating that antenatal neuroprotection may be possible for these newborns at
      high risk for neuroinflammation.

PMID- 25064166
TI  - What is "masked syndrome of inappropriate antidiuretic hormone?" Is it an
      "isonatremic syndrome?".

PMID- 25064167
TI  - Pigmentary and photonic coloration mechanisms reveal taxonomic relationships of
      the Cattlehearts (Lepidoptera: Papilionidae: Parides).
AB  - BACKGROUND: The colorful wing patterns of butterflies, a prime example of
      biodiversity, can change dramatically within closely related species. Wing
      pattern diversity is specifically present among papilionid butterflies. Whether a
      correlation between color and the evolution of these butterflies exists so far
      remained unsolved. RESULTS: We here investigate the Cattlehearts, Parides, a
      small Neotropical genus of papilionid butterflies with 36 members, the wings of
      which are marked by distinctly colored patches. By applying various physical
      techniques, we investigate the coloration toolkit of the wing scales. The wing
      scales contain two different, wavelength-selective absorbing pigments, causing
      pigmentary colorations. Scale ridges with multilayered lamellae, lumen
      multilayers or gyroid photonic crystals in the scale lumen create structural
      colors that are variously combined with these pigmentary colors. CONCLUSIONS: The
      pigmentary and structural traits strongly correlate with the taxonomical
      distribution of Parides species. The experimental findings add crucial insight
      into the evolution of butterfly wing scales and show the importance of
      morphological parameter mapping for butterfly phylogenetics.

PMID- 25064168
TI  - Effects of Internet use on the adolescent brain: despite popular claims,
      experimental evidence remains scarce.
AB  - Twenty-five years have passed since the invention of the World Wide Web changed
      society by allowing unfettered access to the Internet. How this technological
      revolution has affected brain development continues to be an open question. There
      is particular concern about how Internet use is affecting the brains of
      adolescents. This Forum article discusses the possible effects of the Internet,
      as well as the behaviors and capabilities associated with its use, on the
      adolescent brain. 

PMID- 25064169
TI  - Population pharmacokinetic model to analyze nevirapine multiple-peaks profile
      after a single oral dose.
AB  - Nevirapine (NVP) extensive data obtained after oral single dose administration of
      200 mg in a crossover study involving 16 healthy subjects was used to develop a
      descriptive population pharmacokinetic model including drug recirculation, since
      secondary peaks were observed in plasma concentration-time profiles for all
      subjects. Through implementation of model event time feature in NONMEM 7.3.0, a
      simple mechanistic model physiologically consistent with the process of drug
      cycling was able to describe multiple peaks phenomena and quantify its
      pharmacokinetic parameters, achieving a better performance than its analogue
      conventional one. Absorption process, between subject and-between occasion
      variability of pharmacokinetic parameters was also assessed. Estimated mean
      fraction of NVP bioavailable dose undergoing recirculation process was 51.6 %, a
      magnitude which could hardly be explained by enterohepatic cycling. In this work
      we propose an alternative disposition process to explain NVP drug recirculation:
      gastric secretion with posterior intestinal reabsorption. Due to physicochemical
      and pharmacokinetic properties of the drug, this neglected phenomenon is more
      likely to explain the results obtained, and might be present in disposition of
      several basic drugs.

PMID- 25064170
TI  - Association between altered placental human chorionic gonadotrophin (hCG)
      production and the occurrence of cryptorchidism: a retrospective study.
AB  - BACKGROUND: An increase in cryptorchidism has been reported in many countries.
      One mechanism could be low fetal testosterone production possibly secondary to
      altered placental human chorionic gonadotrophin (hCG) release. Our Objective was
      to compare hCG values from maternal blood between boys with cryptorchidism and
      normal boys. METHODS: Total hCG and alpha-fetoprotein (AFP) values [12-16 weeks
      of gestation; from the double test for Down syndrome screening) were compared
      between cases of cryptorchidism and normal control boys who were matched for
      maternal age, maternal smoking, gestational age at time of hCG measurement (+/-1
      day), birth weight and birth term. Measurements were performed in a single
      laboratory; values were expressed as absolute values (KU/L) and multiples of the
      median (MoM). Boys whose mothers had had a complicated pregnancy were excluded.
      Groups were compared using the Student's t test. Log transformation was used to
      normalize hCG, MoM hCG, AFP and MoM AFP distribution, and values were expressed
      as geometric means (-1, + 1 tolerance factor). RESULTS: Total hCG and MoM hCG
      levels were significantly lower in the 51 boys with cryptorchidism compared to
      306 controls (21.4 (12.3; 37) KU/L vs 27.7 (15.9; 47.9) KU/L and 0.8 (0.5; 1.2)
      MoM vs 1.0 (0.6; 1.6) MoM, respectively, p < 0.01). By contrast, AFP and MoM AFP
      levels were similar between groups. CONCLUSION: This study showed a link between
      low maternal serum hCG levels and cryptorchidism in boys from uncomplicated
      pregnancy, while normal AFP levels indicated a normal fetoplacental unit. Whether
      these abnormalities were due to endogenous or exogenous factors remains to be
      determined.

PMID- 25064171
TI  - Phytotoxicity and accumulation of chromium in carrot plants and the derivation of
      soil thresholds for Chinese soils.
AB  - Soil environmental quality standards in respect of heavy metals for farmlands
      should be established considering both their effects on crop yield and their
      accumulation in the edible part. A greenhouse experiment was conducted to
      investigate the effects of chromium (Cr) on biomass production and Cr
      accumulation in carrot plants grown in a wide range of soils. The results
      revealed that carrot yield significantly decreased in 18 of the total 20 soils
      with Cr addition being the soil environmental quality standard of China. The Cr
      content of carrot grown in the five soils with pH>8.0 exceeded the maximum
      allowable level (0.5mgkg(-1)) according to the Chinese General Standard for
      Contaminants in Foods. The relationship between carrot Cr concentration and soil
      pH could be well fitted (R(2)=0.70, P<0.0001) by a linear-linear segmented
      regression model. The addition of Cr to soil influenced carrot yield firstly
      rather than the food quality. The major soil factors controlling Cr phytotoxicity
      and the prediction models were further identified and developed using path
      analysis and stepwise multiple linear regression analysis. Soil Cr thresholds for
      phytotoxicity meanwhile ensuring food safety were then derived on the condition
      of 10 percent yield reduction. 

PMID- 25064173
TI  - Duodenal heterotopic pancreatic tissue: a case report and literature review.
AB  - Heterotopic pancreas is an aberration in the developmental profile of the
      pancreas. This entity is rarely symptomatic and its malignant transformation is
      even rarer. However, when present, it poses a diagnostic dilemma to clinicians,
      as little help comes from gastroenteroscopy and imaging. Surgical exploration
      remains the only option at times, and it is the histopathological examination
      that finally clears the mist. This case report reveals the elusive nature of
      malignancy in heterotopic pancreas in the duodenum. 

PMID- 25064172
TI  - DNA methylation of apoptosis genes in rectal cancer predicts patient survival and
      tumor recurrence.
AB  - Deregulation of the apoptotic pathway, one of the hallmarks of tumor growth and 
      progression, has been shown to have prognostic value for tumor recurrence in
      rectal cancer. In order to develop clinically relevant biomarkers, we studied the
      methylation status of promoter regions of key apoptosis genes in rectal cancer
      patients, using methylation-sensitive restriction enzymes. DNA was extracted from
      fresh-frozen tumor tissues of 49 stage I-III rectal cancer patients and 10 normal
      rectal tissues. The results of this pilot study were validated in 88 stage III
      tumor tissues and 18 normal rectal tissues. We found that methylation of the
      intrinsic apoptotic pathway genes Apaf1, Bcl2 and p53 correlated with the
      apoptotic status (M30) of the tumor. Combined survival analyses of these three
      genes, based on the number of genes showing high methylation (all low, 1 high, 2
      high or all high), showed shorter patient survival and recurrence-free periods
      with an increasing number of methylated markers. Multivariate analyses showed
      significant differences for overall survival (p = 0.01; HR = 0.28 (0.09-0.83)),
      cancer-specific survival (p = 0.004; HR = 0.13 (0.03-0.67)) and distant
      recurrence-free survival (p = 0.001; HR = 0.22(0.05-0.94)). The shortest survival
      was observed for patients showing low methylation of all markers, which-as was
      expected-correlated with high apoptosis (M30), but also with high proliferation
      (Ki-67). The study of epigenetic regulation of apoptosis genes provides more
      insight in the tumorigenic process in rectal cancer and might be helpful in
      further refining treatment regimens for individual patients.

PMID- 25064174
TI  - The role of latanoprost in an inflammatory bowel disease flare.
AB  - Ulcerative colitis and Crohn's disease (CD) are characterized by inflammation of
      the intestinal mucosa and symptoms of abdominal pain and diarrhea. Many studies
      have shown an association between elevated levels of prostaglandins and mucosal
      damage in inflammatory bowel disease. We report a 50-year-old woman with a
      history of CD and open-angle glaucoma. Her glaucoma was treated with latanoprost,
      a prostaglandin analog, which was associated with an exacerbation of her CD. On
      discontinuation of latanoprost, her CD symptoms disappeared completely. This case
      suggests that in a patient with CD, topical administration of latanoprost may
      result in sufficient systemic absorption and circulation to promote a relapse of
      CD. This finding has important implications, not only for patients with
      inflammatory bowel disease and glaucoma, but also for both ophthalmologists and
      gastroenterologists. 

PMID- 25064176
TI  - A prospective study of C-reactive protein as a state marker in Cardiac Syndrome
      X.
AB  - Cardiac Syndrome X (CSX), the presence of angina pectoris despite normal
      epicardial coronary arteries seen on invasive angiography, is known to be
      associated with an elevation of several inflammatory biomarkers, suggesting a
      possible role for inflammation in its pathogenesis. We sought to establish if C
      reactive protein (CRP) levels varied with disease severity and so whether it is a
      state or trait marker. We studied 16 CSX patients with typical angina pectoris,
      normal coronary arteries and an electrically positive exercise stress test (EST)
      and 13 age- and sex-matched healthy controls (HC). CSX patients were followed up
      at a subsequent visit with repeated exercise stress testing and CRP measurement.
      We found that CRP levels were significantly higher in the CSX group compared to
      the HC (1.5 [0.8-4.5] v 0.8 [0.4-1.4] mg/L, p=0.02). This elevation in CRP
      persisted throughout the study length. CRP correlated with time to symptoms on
      EST at enrolment and at the second visit (r=-0.690, df=10, p=0.013 and r=-0.899,
      df=4, p=0.015, respectively). At the follow-up visit, 50% of CSX patients
      developed electrically and symptomatically negative ESTs. The mean CRP of this
      group was significantly lower than that of the CSX patients with ongoing symptoms
      and positive ESTs (1.2+/-0.2 v 2.8+/-0.6mg/L, p=0.018) and did not differ
      significantly from that of healthy controls. CRP levels also dropped in patients
      whose symptoms improved while they increased in patients who became more
      symptomatic (p=0.027). We conclude that the results of this small study support
      the concept of CSX being an inflammatory-mediated condition with CRP levels
      prospectively varying with functional measures of disease severity. This
      indicates that CRP is a state marker in CSX. 

PMID- 25064175
TI  - The role of 18F-FDG PET imaging in upper gastrointestinal malignancies.
AB  - OPINION STATEMENT: Cancers of the upper gastrointestinal tract form a prevalent
      and highly morbid group of malignancies. Specifically, median survival for
      patients with esophagus, gastric, and pancreatic cancers is less than 1 year, and
      although there has been progress in therapeutic strategies, the vast majority of
      newly diagnosed patients with these cancers will die of their disease. (18)F-FDG
      PET ((18)f-fluorodeoxyglucose positron emission tomography) is a useful but
      underutilized resource for identifying metastatic disease in the upper
      gastrointestinal tract. While prevalent in the United States, worldwide, (18)F
      FDG PET is underutilized especially in countries with a growing emergence of
      gastroesophageal cancers, despite evidence of clear benefit in cancer staging,
      and in some cases response assessment and surveillance.

PMID- 25064177
TI  - Neuromodulation and aging: implications of aging neuronal gain control on
      cognition.
AB  - The efficacy of various transmitter systems declines with advancing age. Of
      particular interest, various pre-synaptic and post-synaptic components of the
      dopaminergic system change across the human lifespan; impairments in these
      components play important roles in cognitive deficits commonly observed in the
      elderly. Here, we review evidence from recent multimodal neuroimaging,
      pharmacological and genetic studies that have provided new insights for the
      associations among dopamine functions, aging, functional brain activations and
      behavioral performance across key cognitive functions, ranging from working
      memory and episodic memory to goal-directed learning and decision making.
      Specifically, we discuss these empirical findings in the context of an
      established neurocomputational theory of aging neuronal gain control. We also
      highlight gaps in the current understanding of dopamine neuromodulation and aging
      brain functions and suggest avenues for future research. 

PMID- 25064178
TI  - Descending modulation of pain: the GABA disinhibition hypothesis of analgesia.
AB  - Within the central nervous system, descending systems exist to endogenously
      modulate our perception of pain. Of particular interest is a descending pathway
      which projects via the midbrain periaqueductal grey (PAG) and rostral
      ventromedial medulla (RVM) to inhibit ascending nociceptive transmission at the
      spinal cord dorsal horn. This descending PAG-RVM system forms the circuitry that
      underlies the physiological phenomenon of stress-induced analgesia (SIA), which
      is mediated by parallel opioid and cannabinoid neurotransmitter systems in the
      PAG. At the cellular level, opioids and cannabinoids are hypothesised to activate
      descending analgesia through an indirect process of 'GABA disinhibition'
      suppression of inhibitory GABAergic inputs onto output neurons which constitute
      the descending analgesic pathway. While there is much indirect evidence to
      support disinhibition, there are still questions regarding this model that remain
      unaddressed. Furthermore, there is growing evidence suggesting more complex
      models than originally proposed. 

PMID- 25064180
TI  - Evaluation of endothelial function by peripheral arterial tonometry and relation
      with the nitric oxide pathway.
AB  - Endothelial dysfunction is an important component in the development of
      cardiovascular diseases. Endothelial function may be evaluated by peripheral
      arterial tonometry (PAT) which measures the vasodilator function in the
      microvasculature of the fingertip during reactive hyperaemia. The reactive
      hyperaemia index (RHI) is decreased in the presence of cardiovascular risk
      factors and thus far several studies have shown that PAT-RHI may provide reliable
      prediction of outcome. The technique is operator independent and easy to perform.
      Abnormalities measured by PAT follow the same trend as those measured by flow
      mediated dilation in the brachial artery, but the two methods are not
      interchangeable. We have reviewed the recent literature in an effort to evaluate
      peripheral arterial tonometry as a method to assess the function of the
      endothelium and additionally suggest directions for future research. Special
      attention will be directed to the nitric oxide dependency of the reactive
      hyperaemia index obtained by peripheral arterial tonometry. 

PMID- 25064179
TI  - What optogenetic stimulation is telling us (and failing to tell us) about fast
      neurotransmitters and neuromodulators in brain circuits for wake-sleep
      regulation.
AB  - In the last eight years optogenetic tools have been widely used to identify
      functional synaptic connectivity between specific neuronal populations. Most of
      our knowledge comes from the photo-activation of channelrhodopsin-2 (ChR2)
      expressing inputs that release glutamate and GABA. More recent studies have been
      reporting releases of acetylcholine and biogenic amines but direct evidence for
      photo-evoked released of neuropeptides is still limited particularly in brain
      slice studies. The high fidelity in the responses with photo-evoked amino-acid
      transmission is ideal for ChR2-assisted circuit mapping and this approach has
      been successfully used in different fields of neuroscience. Conversely,
      neuropeptides employ a slow mode of communication and might require higher
      frequency and prolonged stimulations to be released. These factors may have
      contributed to the apparent lack of success for optogenetic release of
      neuropeptides. In addition, once released, neuropeptides often act on multiple
      sites and at various distances from the site of release resulting in a greater
      complexity of postsynaptic responses. Here, we focus on what optogenetics is
      telling us-and failing to tell us-about fast neurotransmitters and neuropeptides.

PMID- 25064182
TI  - Mental health literacy and borderline personality disorder (BPD): what do the
      public "make" of those with BPD?
AB  - INTRODUCTION: This study was part of a programmatic series into mental health
      literacy, specifically lay people's knowledge of causes, manifestations and cures
      of Borderline Personality Disorder (BPD). The aim was to determine to what extent
      non-experts understood BDP and to what extent they held erroneous beliefs about
      specific aspects of the causes and cures for the disorder METHOD: A convenience
      sample of 102 participants completed a vignette-identification task that required
      them to answer open-ended questions about hypothetical people with four
      psychological problems, one of which was BPD and a 50-item questionnaire divided
      into three sections about BDP. RESULTS: Analysis of the vignette identification
      task revealed very low rates of recognition for BPD, with participants
      significantly more likely to identify depression, schizophrenia or psychopathy.
      Participants' generally favoured psychological and sociological treatments, as
      well as rating early trauma and stress as possible causes of the symptoms of the
      person described in the BDP vignette. There were logical relationships between
      perceptions of cause and cure. CONCLUSION: The results suggest that participants
      hold certain coherent beliefs (psychological, sociological, biological or
      theological) regarding aetiology and treatments of BPD. Further, the findings
      suggest the need for greater awareness and educational programmes to inform the
      general public accurately regarding BPD and to improve mental health literacy.

PMID- 25064181
TI  - Nitrosothiol signaling and protein nitrosation in cell death.
AB  - Nitric oxide, a reactive free radical, is an important signaling molecule that
      can lead to a plethora of cellular effects affecting homeostasis. A well
      established mechanism by which NO manifests its effect on cellular functions is
      the post-translational chemical modification of cysteine thiols in substrate
      proteins by a process known as S-nitrosation. Studies that investigate regulation
      of cellular functions through NO have increasingly established S-nitrosation as
      the primary modulatory mechanism in their respective systems. There has been a
      substantial increase in the number of reports citing various candidate proteins
      undergoing S-nitrosation, which affects cell-death and -survival pathways in a
      number of tissues including heart, lung, brain and blood. With an exponentially
      growing list of proteins being identified as substrates for S-nitrosation, it is
      important to assimilate this information in different cell/tissue systems in
      order to gain an overall view of protein regulation of both individual proteins
      and a class of protein substrates. This will allow for broad mapping of proteins
      as a function of S-nitrosation, and help delineate their global effects on
      pathophysiological responses including cell death and survival. This information
      will not only provide a much better understanding of overall functional relevance
      of NO in the context of various disease states, it will also facilitate the
      generation of novel therapeutics to combat specific diseases that are driven by
      NO-mediated S-nitrosation. 

PMID- 25064183
TI  - Dimensional reduction of a V1 ring model with simple and complex cells.
AB  - In this paper, we extend a framework for constructing low-dimensional dynamical
      systems models of mammalian primary visual cortex to a cortical network model
      that incorporates the full nonlinear effects of complex cells. The procedure
      consists of capturing the essential dynamics in a low-dimensional subspace using
      empirical methods, then recasting the equations in the reduced vector space.
      Previously, we considered visual cortical network models consisting of only
      simple cells with nearly linear responses to external stimuli. Here we show that
      fully nonlinear effects can be incorporated by examining the dimensional
      reduction of an idealized ring model of V1 with both simple and complex cells. We
      found it expedient to divide the subspace into four separate neuronal
      populations: excitatory simple, excitatory complex, inhibitory simple and
      inhibitory complex. In order to reproduce the fluctuation-driven dynamics in this
      reduced space, we incorporated (1) white noises with different intensities into
      individual neuronal populations, and (2) firing rate estimates to capture the
      probability of firing due to subthreshold fluctuations. With a more accurate,
      fitted connectivity, our modified dimensional reduced models can reproduce the
      firing rates, circular variances and modulation ratios observed in the original
      ring model. 

PMID- 25064184
TI  - Analysis of sources of bulk conductivity change in saturated silica sand after
      unbuffered TCE oxidation by permanganate.
AB  - Time lapse resistivity surveys could potentially improve monitoring of
      permanganate-based in situ chemical oxidation (ISCO) of organic contaminants such
      as trichloroethene (TCE) by tracking changes in subsurface conductivity that
      result from injection of permanganate and oxidation of the contaminant. Bulk
      conductivity and pore fluid conductivity changes during unbuffered TCE oxidation
      using permanganate are examined through laboratory measurements and conductivity
      modeling using PHREEQC in fluid samples and porous media samples containing
      silica sand. In fluid samples, oxidation of one TCE molecule produces three
      chloride ions and one proton, resulting in an increase in fluid electrical
      conductivity despite the loss of two permanganate ions in the reaction. However,
      in saturated sand samples in which up to 8mM TCE was oxidized, at least 94% of
      the fluid conductivity associated with the presence of protons was removed within
      3h of sand contact, most likely through protonation of silanol groups found on
      the surface of the sand grains. Minor conductivity effects most likely associated
      with pH-dependent reductive dissolution of manganese dioxide were also observed
      but not accounted for in pore-fluid conductivity modeling. Unaccounted
      conductivity effects resulted in an under-calculation of post-reaction pore fluid
      conductivity of 2.1% to 5.5%. Although small increases in the porous media
      formation factor resulting from precipitation of manganese dioxide were detected
      (about 3%), these increases could not be confirmed to be statistically
      significant. Both injection of permanganate and oxidation of TCE cause increases
      in bulk conductivity that would be detectable through time-lapse resistivity
      surveys in field conditions. 

PMID- 25064185
TI  - Formation of cholinergic synapse-like specializations at developing murine muscle
      spindles.
AB  - Muscle spindles are complex stretch-sensitive mechanoreceptors. They consist of
      specialized skeletal muscle fibers, called intrafusal fibers, which are
      innervated in the central (equatorial) region by afferent sensory axons and in
      both polar regions by efferent gamma-motoneurons. We show that AChRs are
      concentrated at the gamma-motoneuron endplate as well as in the equatorial region
      where they colocalize with the sensory nerve ending. In addition to the AChRs,
      the contact site between sensory nerve ending and intrafusal muscle fiber
      contains a high concentration of choline acetyltransferase, vesicular
      acetylcholine transporter and the AChR-associated protein rapsyn. Moreover,
      bassoon, a component of the presynaptic cytomatrix involved in synaptic vesicle
      exocytosis, is present in gamma-motoneuron endplates but also in the sensory
      nerve terminal. Finally, we demonstrate that during postnatal development of the
      gamma-motoneuron endplate, the AChR subunit stoichiometry changes from the gamma
      subunit-containing fetal AChRs to the epsilon-subunit-containing adult AChRs,
      similar and approximately in parallel to the postnatal subunit maturation at the
      neuromuscular junction. In contrast, despite the onset of epsilon-subunit
      expression during postnatal development the gamma-subunit remains detectable in
      the equatorial region by subunit-specific antibodies as well as by analysis of
      muscle spindles from mice with genetically-labeled AChR gamma-subunits. These
      results demonstrate an unusual maturation of the AChR subunit composition at the
      annulospiral endings and suggest that in addition to the recently described
      glutamatergic secretory system, the sensory nerve terminals are also specialized
      for cholinergic synaptic transmission, synaptic vesicle storage and exocytosis. 

PMID- 25064186
TI  - Shear wave velocities in damaged kidneys: fast and slow.

PMID- 25064187
TI  - Acoustic radiation force impulse (ARFI) elastography for detection of renal
      damage in children.
AB  - BACKGROUND: Acoustic radiation force impulse (ARFI) imaging is a promising method
      for noninvasive evaluation of the renal parenchyma. OBJECTIVE: To investigate the
      contribution of ARFI quantitative US elastography for the detection of renal
      damage in kidneys with and without vesicoureteral reflux (VUR). MATERIALS AND
      METHODS: One hundred seventy-six kidneys of 88 children (46 male, 42 female) who
      had been referred for voiding cystourethrography and 20 healthy controls were
      prospectively investigated. Patients were assessed according to severity of renal
      damage on dimercaptosuccinic acid (DMSA) scintigraphy. Ninety-eight age- and
      gender-matched healthy children constituted the control group. Quantitative shear
      wave velocity (SWV) measurements were performed in the upper and lower poles and
      in the interpolar region of each kidney. DMSA scintigraphy was performed in 62
      children (124 kidneys). Comparisons of SWV values of kidneys with and without
      renal damage and/or VUR were done. RESULTS: Significantly higher SWV values were
      found in non-damaged kidneys. Severely damaged kidneys had the lowest SWV values
      (P < 0.001). High-grade (grade V-IV) refluxing kidneys had the lowest SWV values,
      while non-refluxing kidneys had the highest values (P < 0.05). Significant
      negative correlations were found between the mean quantitative US elastography
      values and DMSA scarring score (r = -0.788, P < 0.001) and VUR grade (r = -0.634,
      P < 0.001). SWV values of the control kidneys were significantly higher than
      those of damaged kidneys (P < 0.05). CONCLUSION: Our findings suggest decreasing
      SWV of renal units with increasing grades of vesicoureteric reflux, increasing
      DMSA-assessed renal damage and decreasing DMSA-assessed differential function.

PMID- 25064189
TI  - NEDE: an open-source scripting suite for developing experiments in 3D virtual
      environments.
AB  - BACKGROUND: As neuroscientists endeavor to understand the brain's response to
      ecologically valid scenarios, many are leaving behind hyper-controlled paradigms
      in favor of more realistic ones. This movement has made the use of 3D rendering
      software an increasingly compelling option. However, mastering such software and
      scripting rigorous experiments requires a daunting amount of time and effort. NEW
      METHOD: To reduce these startup costs and make virtual environment studies more
      accessible to researchers, we demonstrate a naturalistic experimental design
      environment (NEDE) that allows experimenters to present realistic virtual stimuli
      while still providing tight control over the subject's experience. NEDE is a
      suite of open-source scripts built on the widely used Unity3D game development
      software, giving experimenters access to powerful rendering tools while
      interfacing with eye tracking and EEG, randomizing stimuli, and providing custom
      task prompts. RESULTS: Researchers using NEDE can present a dynamic 3D virtual
      environment in which randomized stimulus objects can be placed, allowing subjects
      to explore in search of these objects. NEDE interfaces with a research-grade eye
      tracker in real-time to maintain precise timing records and sync with EEG or
      other recording modalities. COMPARISON WITH EXISTING METHODS: Python offers an
      alternative for experienced programmers who feel comfortable mastering and
      integrating the various toolboxes available. NEDE combines many of these
      capabilities with an easy-to-use interface and, through Unity's extensive user
      base, a much more substantial body of assets and tutorials. CONCLUSIONS: Our
      flexible, open-source experimental design system lowers the barrier to entry for
      neuroscientists interested in developing experiments in realistic virtual
      environments.

PMID- 25064188
TI  - An organotypic brain slice preparation from adult patients with temporal lobe
      epilepsy.
AB  - BACKGROUND: A long-term in vitro preparation of diseased brain tissue would
      facilitate work on human pathologies. Organotypic tissue cultures retain an
      appropriate neuronal form, spatial arrangement, connectivity and electrical
      activity over several weeks. However, they are typically prepared with tissue
      from immature animals. In work using tissue from adult animals or humans,
      survival times longer than a few days have not been reported and it is not clear
      that pathological neuronal activities are retained. NEW METHOD: We modified
      tissue preparation procedures and used a defined culture medium to make
      organotypic cultures of temporal lobe tissue obtained after operations on adult
      patients with pharmaco-resistant mesial temporal lobe epilepsies. RESULTS:
      Organototypic culture preparation and maintenance techniques were judged on
      criteria of morphology and the generation of epileptiform activities. Short
      duration (30-100 ms) interictal-like population activities were initiated
      spontaneously in either the subiculum, dentate gyrus or the CA2/CA3 region, but
      not the cortex, for up to 3-4 weeks in culture. Ictal-like discharges, of
      duration greater than 10s, were induced by convulsants. Epileptiform activities
      were modulated by both glutamatergic and GABAergic receptor antagonists.
      COMPARISON WITH EXISTING METHODS: Our methods now permit the maintenance in
      organotypic culture of epileptic adult human tissue, generating appropriate
      epileptiform activity over 3-4 weeks. CONCLUSIONS: We have shown that
      characteristic morphology and pathological activities are maintained in
      organotypic cultures of adult human tissue. These cultures should permit studies
      on the effects of prolonged drug treatments and long-term procedures such as
      viral transduction.

PMID- 25064190
TI  - Cost-efficient method and device for the study of stationary tissular gas bubble
      formation in the mechanisms of decompression sickness.
AB  - BACKGROUND: Current in vivo methods cannot distinguish between the roles of
      vascular and stationary tissular gas bubbles in the mechanisms of decompression
      sickness (DCS). NEW METHOD: To answer this question, we designed a normobaric
      hyperbaric chamber for studying specifically the contribution of stationary
      tissular gas bubbles in the mechanisms of DCS in individually-superfused tissue
      samples. For validating our method, we investigated in rat brain slices exposed
      to 0.4MPa air absolute pressure whether fast decompression rate - the most
      important cause of cerebral DCS - may induce an increase of lactate dehydrogenase
      (LDH), a marker of cell injury, compared to slow decompression rate. RESULTS: We
      provide a technical description of our pressure chamber and show that fast
      decompression rate of 0.3MPamin(-1) induced a rapid and sustained increase of LDH
      release compared to slow compression rate of 0.01MPamin(-1) (P<0.0001).
      COMPARISON WITH EXISTING METHODS: There is no current method for studying
      stationary tissular gas bubbles. CONCLUSIONS: This report describes the first
      method for studying specifically in tissue samples the role of stationary
      tissular gas bubbles in the mechanisms of DCS. Advantageously, according to this
      method (i) biological markers other than LDH could be easily studied; (ii) tissue
      samples could be taken not only from the brain but also from any part of the
      animal's body known of interest in DCS research, allowing performing tissue
      compartment research, a major question in the physics and theory of decompression
      research; and (iii) histological studies could be performed from the tissue
      samples.

PMID- 25064191
TI  - An MRI-compatible caloric stimulation device for the investigation of human
      vestibular cortex.
AB  - BACKGROUND: Self-motion perception involves the integration of vestibular,
      visual, somatosensory and other sensory cues. The neural responses to caloric
      vestibular stimulation (CVS) in humans have been investigated with functional
      magnetic resonance imaging (fMRI). NEW METHOD: We developed an fMRI-compatible,
      bithermal caloric stimulation device for repeated CVS. Tempered water is pumped
      via a closed-loop tube-system to one or both ear canals. Water temperature
      transmits to the surface of the ear canal via a small glass-pod. For our purposes
      we used hot (47-49 degrees C), cold (5-7.5 degrees C), or warm for baseline (30
      32.5 degrees C). The pods are integrated in the MRI ear protection and connected
      to water influx and efflux tubes. With our device we can apply multiple
      vestibular stimulation and baseline trials consecutively. Control measurements
      indicate that the applied temperatures are stable across trials. MRI-signal
      differences due to water flow and water temperature are restricted to the area
      surrounding the pod and are unlikely to intrude into brain tissue. RESULTS:
      Vestibular stimulation with our device elicits caloric nystagmus when no central
      fixation is presented. We validated our system by conducting a CVS experiment
      during fMRI-scanning. Participants indicated the presence or absence of a self
      motion sensation. Periods of self motion yielded activation in the cortical
      vestibular network including putative human parieto-insular vestibular cortex
      (PIVC). COMPARISON WITH EXISTING METHODS: Our closed-loop device eliminates many
      problems associated with caloric stimulation during fMRI. CONCLUSIONS: Our device
      allows researchers to explore neural responses to CVS and those evoked by
      combined sensory stimulation.

PMID- 25064192
TI  - Appetite stimulants for people with cystic fibrosis.
AB  - BACKGROUND: Chronic loss of appetite in cystic fibrosis concerns both individuals
      and families. Appetite stimulants have been used to help cystic fibrosis patients
      with chronic anorexia attain optimal body mass index and nutritional status.
      However, these may have adverse effects on clinical status. OBJECTIVES: The aim
      of this review is to systematically search for and evaluate evidence on the
      beneficial effects of appetite stimulants in the management of CF-related
      anorexia and synthesize reports of any side-effects. SEARCH METHODS: Trials were
      identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders
      Group's Cystic Fibrosis Trials Register, MEDLINE, Embase, CINAHL, handsearching
      reference lists and contacting local and international experts.Last search of
      online databases: 01 April 2014.Last search of the Cystic Fibrosis Trials
      Register: 08 April 2014. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled trials of appetite stimulants, compared to placebo or no treatment for
      at least one month in adults and children with cystic fibrosis. DATA COLLECTION
      AND ANALYSIS: Authors independently extracted data and assessed the risk of bias
      within eligible trials. Meta-analyses were performed. MAIN RESULTS: Three trials
      (total of 47 recruited patients) comparing appetite stimulants (cyproheptadine
      hydrochloride and megesterol acetate) to placebo were included; the numbers of
      adults or children within each trial were not always reported. The risk of bias
      of the included trials was graded as moderate.A meta-analysis of all three trials
      showed appetite stimulants produced a larger increase in weight z score at three
      months compared to placebo, mean difference 0.61 (95% confidence interval 0.29 to
      0.93) (P < 0.001) (n = 40) with no evidence of a difference in effect between two
      different appetite stimulants. One of these trials also reported a significant
      weight increase with megesterol acetate compared to placebo at six months (n =
      17). The three trials reported no significant differences in forced expiratory
      volume at one second (per cent predicted) between the appetite stimulant groups
      and placebo at follow up, with durations ranging from two to nine months. A meta
      analysis of two trials showed a significantly higher proportion of patients
      reporting increased appetite, odds ratio 45.25 (95% confidence interval 3.57 to
      573.33) (P = 0.003) (n = 23), but the frequency of reported side effects was
      undetermined. AUTHORS' CONCLUSIONS: In the short term (six months) in adults and
      children, appetite stimulants improved only two of the outcomes in this review -
      weight (or weight z score) and appetite; and side effects were insufficiently
      reported to determine the full extent of their impact. Whilst the data may
      suggest the potential use of appetite stimulants in treating anorexia in adults
      and children with cystic fibrosis, this is based upon moderate quality data from
      a small number of trials and so this therapy cannot be conclusively recommended
      based upon the findings in the review. Clinicians need to be aware of the
      potential adverse effects of appetite stimulants and actively monitor any
      patients prescribed these medications accordingly.Research is needed to determine
      meaningful surrogate measures for appetite and define what constitutes quality
      weight gain. Future trials of appetite stimulants should use a validated measure
      of symptoms including a disease-specific instrument for measuring poor appetite.
      This review highlights the need for multicentred, adequately powered and well
      designed trials to evaluate agents to safely increase appetite in people with
      cystic fibrosis and to establish the optimal mode of treatment.

PMID- 25064193
TI  - Enhancing performance during inclined loaded walking with a powered ankle-foot
      exoskeleton.
AB  - PURPOSE: A simple ankle-foot exoskeleton that assists plantarflexion during push
      off can reduce the metabolic power during walking. This suggests that walking
      performance during a maximal incremental exercise could be improved with an
      exoskeleton if the exoskeleton is still efficient during maximal exercise
      intensities. Therefore, we quantified the walking performance during a maximal
      incremental exercise test with a powered and unpowered exoskeleton: uphill
      walking with progressively higher weights. METHODS: Nine female subjects
      performed two incremental exercise tests with an exoskeleton: 1 day with (powered
      condition) and another day without (unpowered condition) plantarflexion
      assistance. Subjects walked on an inclined treadmill (15%) at 5 km h(-1) and 5%
      of body weight was added every 3 min until exhaustion. RESULTS: At volitional
      termination no significant differences were found between the powered and
      unpowered condition for blood lactate concentration (respectively, 7.93 +/- 2.49;
      8.14 +/- 2.24 mmol L(-1)), heart rate (respectively, 190.00 +/- 6.50; 191.78 +/-
      6.50 bpm), Borg score (respectively, 18.57 +/- 0.79; 18.93 +/- 0.73) and VO2 peak
      (respectively, 40.55 +/- 2.78; 40.55 +/- 3.05 ml min(-1) kg(-1)). Thus, subjects
      were able to reach the same (near) maximal effort in both conditions. However,
      subjects continued the exercise test longer in the powered condition and carried
      7.07 +/- 3.34 kg more weight because of the assistance of the exoskeleton.
      CONCLUSION: Our results show that plantarflexion assistance during push-off can
      increase walking performance during a maximal exercise test as subjects were able
      to carry more weight. This emphasizes the importance of acting on the ankle joint
      in assistive devices and the potential of simple ankle-foot exoskeletons for
      reducing metabolic power and increasing weight carrying capability, even during
      maximal intensities.

PMID- 25064194
TI  - Critical power: what is being measured and why?

PMID- 25064195
TI  - "Optimal" cutoff value of heart rate; appraisal based on heart rate variability
      and C-reactive protein.

PMID- 25064196
TI  - Is pulse pressure a predictor of diabetes in Chinese Han nationality population?
      15-year prospective study in Chengdu community.

PMID- 25064197
TI  - Patients selection for MitraClip: time to move to transthoracic echocardiographic
      screening?

PMID- 25064198
TI  - Kounis syndrome following cold urticaria: the swimmer's death.

PMID- 25064199
TI  - Prolonged length of hospital stay in Far-East Asian and Afro-Caribbean patients
      with cardiomyopathy.

PMID- 25064200
TI  - A monounsaturated fatty acid (oleic acid) modulates electrical activity in atrial
      myocytes with calcium and sodium dysregulation.
AB  - BACKGROUND: Obesity and metabolic syndrome are important risk factors for atrial
      fibrillation. High plasma concentrations of monounsaturated fatty acids,
      including oleic acid (OLA), are frequently noted in obese individuals and
      patients with metabolic syndrome. However, it is not clear whether
      monounsaturated fatty acids (MUFAs) can directly modulate the
      electrophysiological characteristics of atrial myocytes. METHODS: Whole-cell
      patch clamp, indo-1 fluorescence, and Western blot analyses were used to record
      the action potentials (APs), ionic currents, and protein expressions of HL-1
      myocytes incubated with and without (control) OLA (0.5mM) for 24h. RESULTS:
      Compared to control myocytes (n=14), OLA-treated myocytes (n=16) had shorter
      APD90 (65 +/- 6 vs. 85 +/- 6 ms, p<0.05) and APD50 (24 +/- 6 vs. 38 +/- 4 ms,
      p<0.05) with a higher incidence of delayed afterdepolarizations (35.7% vs. 7%,
      p<0.05), which were suppressed by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid (DIDS, a blocker of the calcium-activated chloride current). In addition,
      OLA-treated myocytes (n=19) exhibited larger calcium transients (0.54 +/- 0.06
      vs. 0.38 +/- 0.05 R410/485, p<0.05), and sarcoplasmic reticular calcium contents
      (0.91 +/- 0.05 vs. 0.64 +/- 0.08 R410/485, p<0.05) than control myocytes (n=15).
      OLA-treated myocytes had larger late sodium currents, smaller sodium-calcium
      exchanger currents, and smaller sodium-potassium pump currents. Moreover OLA
      treated myocytes had higher expressions of sarcoplasmic reticular Ca(2+)-ATPase
      and calmodulin kinase II, but lower expression of the sodium-potassium ATPase
      protein than control myocytes. CONCLUSIONS: MUFAs can regulate atrial
      electrophysiological characteristics with calcium and sodium dysregulation, which
      may contribute to atrial arrhythmogenesis.

PMID- 25064201
TI  - No-kiss sleeve: a technical modification of the sleeve technique to treat true
      bifurcation lesions in the bioresorbable vascular scaffold era.

PMID- 25064203
TI  - Response to Letter by Mkrtchyan regarding article: "Aortic biomechanics by
      magnetic resonance: early markers of aortic disease in Marfan syndrome regardless
      of aortic dilatation?".

PMID- 25064202
TI  - Sleep apnea prevalence in acute myocardial infarction--the Sleep Apnea in Post
      acute Myocardial Infarction Patients (SAPAMI) Study.
AB  - BACKGROUND: While sleep apnea (SA) might be a modifiable cardiovascular risk
      factor, recent data suggest that SA is severely underdiagnosed in patients after
      acute myocardial infarction (MI). There is limited evidence about day-night
      variation of onset of MI on dependence of having SA. We therefore investigated
      the prevalence of SA and examined the day-night variation of onset of MI in acute
      MI patients. METHODS: We prospectively studied 782 consecutive patients admitted
      to the hospital with the diagnosis of acute MI. All subjects underwent sleep
      evaluations using a portable device after at least 48 h post-admission. Using the
      apnea-hypopnea index (AHI), groups were defined as patients without SA (<5
      events/h), mild SA (5-15 events/h), moderate SA (15-30 events/h), and severe SA
      (>= 30 events/h). RESULTS: Almost all patients (98%) underwent urgent coronary
      angiography and 91% of patients underwent primary PCI. Using a threshold of AHI
      >= 5 events/h, SA was present in 65.7% of patients after acute MI. Mild SA was
      present in 32.6%, moderate in 20.4% and severe in 12.7%. The day-night variation
      in the onset of MI in all groups of SA patients was similar to that observed in
      non-SA patients. From 6 AM to 12 PM, the frequency of MI was higher in both SA
      and non-SA patients, as compared to the interval from 12 AM to 6 AM (all p<0.05).
      CONCLUSION: There is a high prevalence of SA in patients presenting with acute
      MI. Peak time of MI onset in SA patients was between 6 AM and noon, similar to
      that in the general population. Whether diagnosis and treatment of SA after MI
      will significantly improve outcomes in these patients remains to be determined.

PMID- 25064204
TI  - CCR5 chemokine receptor gene variants in chronic Chagas' disease.

PMID- 25064205
TI  - Vascular effects of circulating CD4-T cells in patients with unstable angina.

PMID- 25064206
TI  - Maternal lipid profile during early pregnancy and their children's blood pressure
      and cardiac autonomic balance at age 5-6 years.

PMID- 25064207
TI  - Normative data for the Hospital Anxiety and Depression Scale.
AB  - PURPOSE: The Hospital Anxiety and Depression Scale (HADS) is widely used in both
      research and clinical contexts. However, UK normative data from HADS remain
      limited. In our recent review of the literature, only six reports from four
      studies were identified as reporting UK normative data and all had limitations.
      The aim of our study was to use a large population-based dataset to address this.
      METHODS: The Epidemiology of Functional Disorders Study is a large longitudinal
      population-based study carried out in Northwest England. All adults aged between
      25 and 65 years registered with three general practices were sent a self
      completion questionnaire which contained the HADS and other health-related
      instruments. Scores were calculated for participants completing all items on each
      sub-scale (anxiety 6,189 participants and depression 6,198 participants). Scores
      are presented by gender and by 5-year age groups. Percentile scores were also
      generated. RESULTS: The median anxiety score was higher in women [6,
      interquartile range (IQR) 4-9] than in men (5, IQR 2-8) and increased with age in
      both groups. The median depression score for both women and men was 3 (IQR 1-6).
      CONCLUSIONS: Our study is the largest population-based study providing UK
      normative data from the HADS. While our data confirm some of the normative data
      reported previously, subtle and important differences emerged, particularly at
      the upper end of the percentile scores. Due to the nature of our study design and
      the number of participants sampled, we believe that our data are likely to be
      more representative of the UK population than existing published normative
      values.

PMID- 25064208
TI  - Systematically searching for and assessing the literature for self-management of
      chronic pain: a lay users' perspective.
AB  - BACKGROUND: The Engaging with older adults in the development of strategies for
      the self management of chronic pain (EOPIC) study aims to design and develop self
      management strategies to enable older adults to manage their own pain. Involving
      older adults in research into chronic pain management will better enable the
      identification and development of strategies that are more appropriate for their
      use, but how can perspectives really be utilised to the best possible outcomes?
      METHOD: Seven older adults were recruited through a local advertising campaign to
      take part. We also invited participants from the local pain services, individuals
      who had been involved in earlier phase of the EOPIC study and a previous ESRC
      funded project. The group undertook library training and research skills training
      to facilitate searching of the literature and identified sources of material. A
      grading tool was developed using perceived essential criteria identified by the
      older adults and material was graded according to the criteria within this scale.
      RESULTS: Fifty-seven resources from over twenty-eight sources were identified.
      These materials were identified as being easily accessible, readable and
      relevant. Many of the web based materials were not always easy to find or readily
      available so they were excluded by the participants. All but one were UK based.
      Forty-four items were identified as meeting the key criteria for inclusion in the
      study. This included five key categories as follows; books, internet, magazines,
      leaflets, CD's/Tapes. CONCLUSION: This project was able to identify a number of
      exemplars of self management material along with some general rules regarding the
      categories identified. We must point out that the materials identified were not
      age specific, were often locally developed and would need to be adapted to older
      adults with chronic pain. For copyright issues we have not included them in this
      paper. The key message is really related to the format rather than the content.
      However, the group acknowledge that these may vary according to the requirements
      of each individual older adult and therefore recommend the development of a
      leaflet to help others in their search for resources. This leaflet has been
      developed as part of Phase IV of the EOPIC study.

PMID- 25064209
TI  - Understanding CBHI hospitalisation patterns: a comparison of insured and
      uninsured women in Gujarat, India.
AB  - BACKGROUND: Community-based health insurance has been associated with increased
      hospitalisation in low-income settings, but with limited analysis of the
      illnesses for which claims are submitted. A review of claims submitted to
      VimoSEWA, an inpatient insurance scheme in Gujarat, India, found that fever,
      diarrhoea and hysterectomy, the latter at a mean age of 37 years, were the
      leading reasons for claims by adult women. We compared the morbidity, outpatient
      treatment-seeking and hospitalisation patterns of VimoSEWA-insured women with
      uninsured women. METHODS: We utilised data from a cross-sectional survey of 1,934
      insured and uninsured women in Gujarat, India. Multivariable logistic regression
      identified predictors of insurance coverage and the association of insurance with
      hospitalisation. Self-reported data on morbidity, outpatient care and
      hospitalisation were compared between insured and uninsured women. RESULTS: Age,
      marital status and occupation of adult women were associated with insurance
      status. Reported recent morbidity, type of illness and outpatient treatment were
      similar among insured and uninsured women. Multivariable analysis revealed strong
      evidence of a higher odds of hospitalisation amongst the insured (OR = 2.7; 95%
      ci. 1.6, 4.7). The leading reason for hospitalisation for uninsured and insured
      women was hysterectomy, at a similar mean age of 36, followed by common ailments
      such as fever and diarrhoea. Insured women appeared to have a higher probability
      of being hospitalised than uninsured women for all causes, rather than
      specifically for fever, diarrhoea or hysterectomy. Length of stay was similar
      while choice of hospital differed between insured and uninsured women.
      CONCLUSIONS: Despite similar reported morbidity patterns and initial treatment
      seeking behaviour, VimoSEWA members were more likely to be hospitalised. The data
      did not provide strong evidence that inpatient hospitalisation replaced
      outpatient treatment for common illnesses or that insurance was the primary
      inducement for hysterectomy in the population. Rather, it appears that VimoSEWA
      members behaved differently in deciding if, and where, to be hospitalised for any
      condition. Further research is required to explore this decision-making process
      and roles, if any, played by adverse selection and moral hazard. Lastly, these
      hospitalisation patterns raise concerns regarding population health needs and
      access to quality preventive and outpatient services.

PMID- 25064210
TI  - Updates in biological therapies for knee injuries: menisci.
AB  - The preservation of meniscal tissue is paramount for long-term joint function,
      especially in younger patients who are athletically active. Many studies have
      reported encouraging results following the repair of meniscus tears, including
      both simple longitudinal tears located in the periphery and complex multiplanar
      tears that extend into the central third avascular region. However, most types of
      meniscal lesions are managed with a partial meniscectomy. Options to restore the
      meniscus range from an allograft transplantation to the use of synthetic and
      biological technologies. Recent studies have demonstrated good long-term outcomes
      with meniscal allograft transplantation, although the indications and techniques
      continue to evolve, and the long-term chondroprotective potential of this
      approach has yet to be determined. Several synthetic implants, most of which are
      approved in the European market, have shown some promise for replacing part of or
      the entire meniscus, including collagen meniscal implants, hydrogels, and polymer
      scaffolds. Currently, there is no ideal implant generated by means of tissue
      engineering. However, meniscus tissue engineering is a fast developing field that
      promises to develop an implant that mimics the histologic and biomechanical
      properties of a native meniscus. 

PMID- 25064211
TI  - Improving the scalability of psychological treatments in developing countries: an
      evaluation of peer-led therapy quality assessment in Goa, India.
AB  - Psychological treatments delivered by lay therapists, with little or no previous
      mental health training, have been shown to be effective in treating a range of
      mental health problems. In low resource settings, the dearth of available experts
      to assess therapy quality potentially leads to a bottleneck in scaling up lay
      therapist delivered psychological treatments. Peer-led supervision and the
      assessment of therapy quality may be one solution to address this barrier. The
      purpose of this study was two-fold: 1) to assess lay therapist quality ratings
      compared to expert supervisors in a multisite study where lay therapists
      delivered two locally developed, psychological treatments for harmful and
      dependent drinking and severe depression; 2) assess the acceptability and
      feasibility of peer-led supervision compared to expert-led supervision. We
      developed two scales, one for each treatment, to compare lay therapist and expert
      ratings on audio-taped treatment sessions (n = 189). Our findings confirmed our
      primary hypothesis of increased levels of agreement between peer and expert
      ratings over three consecutive time periods as demonstrated by a decrease in the
      differences in mean therapy quality rating scores. This study highlights that lay
      therapists can be trained to effectively assess each other's therapy sessions as
      well as experts, and that peer-led supervision is acceptable for lay therapists,
      thus, enhancing the scalability of psychological treatments in low-resource
      settings.

PMID- 25064212
TI  - Predictors of Urgent Findings on Abdominopelvic CT in Patients with Crohn's
      Disease Presenting to the Emergency Department.
AB  - BACKGROUND: Patients with Crohn's disease (CD) are frequently exposed to
      diagnostic radiation, mainly as a result of abdominopelvic computed tomography
      (APCT) examinations. However, there are limited data on the impact of APCT on
      clinical management in this population. AIM: To investigate clinical predictors
      of urgent findings on APCT in patients with CD who presented to the emergency
      department (ED). METHODS: A retrospective study was performed among patients with
      CD presenting to 11 EDs with a gastrointestinal complaint. The primary outcome,
      OPAN (obstruction, perforation, abscess, or non-CD-related urgent findings),
      included new or worsening CD-related urgent findings or non-CD-related urgent
      findings that required urgent or emergency treatment. Variables with P < 0.1 in
      univariate analyses were included in a multivariable logistic regression model.
      RESULTS: Of the 266 APCTs performed, 103 (38.7 %) had OPAN and 113 (42.5 %)
      required changes in treatment plan. Stricturing or penetrating disease (odds
      ratio [OR] 2.72, 95 % confidence interval [CI] 1.21-6.13), heart rate >100
      beats/min (OR 2.33, 95 % CI 1.10-4.93), leukocyte count >10,000/mm(3) (OR 4.38,
      95 % CI 2.10-9.13), and CRP >2.5 mg/dL (OR 3.11, 95 % CI 1.23-7.86) were
      identified as the independent predictors of OPAN, whereas biologic agent use (OR
      0.37; 95 % CI 0.15-0.90) was identified as the negative predictor in patients
      with CD. CONCLUSIONS: Only 39 % of the APCTs performed in the ED among patients
      with CD showed urgent findings. Stricturing or penetrating disease, tachycardia,
      leukocytosis, and high CRP level were predictors of urgent CT findings, while
      biologic agent use was a negative predictor. To reduce unnecessary radiation
      exposure, the selection process for CD patients referred for APCT must be
      improved.

PMID- 25064213
TI  - Ischemia-reperfusion injury and regrowth of liver cancers: to clamp or not to
      clamp?

PMID- 25064214
TI  - Factors related to readmission after major elective surgery.
AB  - BACKGROUND: Hospital readmissions have received increased scrutiny as a marker
      for excessive resource utilization and also quality care. AIM: To identify the
      rate of and risk factors for hospital readmission after major surgery at academic
      medical centers. METHODS: Using the University Health Consortium Clinical
      Database, 30-day readmission rates in all adult patients undergoing colectomy (n
      = 103,129), lung resection (n = 73,558), gastric bypass (n = 62,010) or abdominal
      aortic surgery (n = 17,997) from 2009 to 2012 were identified. Logistic
      regression was performed to examine risks for readmission. RESULTS: Overall
      readmission rates ranged from 8.9 % after gastric bypass to 15.8 % after
      colectomy. Black race was associated with increased likelihood for readmission
      after three of the four procedures with odds ratios ranging from 1.13 after
      colectomy to 1.44 after gastric bypass. For all procedures, moderate, severe, or
      extreme severity of illness (SOI) and need for transitional care were associated
      with increased odds for hospital readmission. Lower center volume was an
      independent predictor of readmission after gastric bypass surgery and aortic
      surgery. CONCLUSION: Readmission rates after major elective surgery are high
      across national academic centers. Center volume, SOI, and need for transitional
      care after discharge are factors associated with readmission and may be used to
      identify patients at high risk of readmission and hospital utilization after
      major surgery.

PMID- 25064215
TI  - New amino butenolides from the bulbs of Fritillaria unibracteata.
AB  - Five new amino gamma-butenolides, fritenolide A (1), B (2), C (3), D (4), and E
      (5), along with four known compounds, were isolated from the bulbs of Fritillaria
      unibracteata. Their structures were determined by spectroscopic analysis,
      including 1D NMR, 2D NMR, HRESIMS, HRESIMS/MS, IR, and CD techniques. All
      isolates were evaluated for the protective activity on injured hepatocytes and
      cytotoxic activity on human cancer cells in vitro. The unusual amino butenolides
      were isolated from the Liliaceae family for the first time.

PMID- 25064216
TI  - Synthesis and anti-cancer activity of naturally occurring 2,5-diketopiperazines.
AB  - Three naturally occurring oxyprenylated diketopiperazines were synthesized and
      preliminarily tested as growth inhibitory agents in vitro against various cancer
      cell lines. The compounds were tested on six human cancer cell lines with
      different sensitivity to proapoptotic stimuli using the MTT colorimetric assay.
      The data revealed that of the chemicals under study only deoxymicelianamide (11)
      displayed the highest activity, recording mean IC50 growth inhibitory values
      ranging from 2 to 23 MUM. A comparative study with the non-geranylated saturated
      derivative of (11) revealed the importance of the presence of the geranyloxy side
      chain and the exocyclic 2,5-DPK double bond moiety for the observed activity.

PMID- 25064217
TI  - A retrospective analysis of ten symptomatic multiple myeloma patients with HIV
      infection: a potential therapeutic effect of HAART in multiple myeloma.
AB  - The impact of highly active anti-retroviral therapy (HAART) in multiple myeloma
      (MM) is unknown. Ten HIV+ and 28 HIV-negative patients were retrospectively
      identified out of 262 cases of MM diagnosed at Kings County Hospital Center since
      the introduction of HAART in 1996. The HIV+ MM patients on HAART had superior
      overall survival (OS) (Fisher exact, p=0.008; log-rank, p=0.012) and progression
      free survival (PFS) (Fisher exact, p=0.007; log-rank, p=0.009) than the HIV
      negative MM patients. HAART alone blocked the production of serum M-protein. We
      propose that HARRT should be explored for the treatment of both HIV+ and HIV
      negative MM patients. 

PMID- 25064219
TI  - MicroRNA-2 suppresses Lewis lung cancer cells proliferation, invasion, and
      migration in tumor-bearing mice.
AB  - We sought to find the biological effects of MicroRNA-2 in suppressing Lewis lung
      cancer cells proliferation, invasion, and migration in tumor-bearing mice.
      MicroRNA-2 was transfected into Lewis lung cancer cells of tumor-bearing mice by
      gene transient transfection technique and these Lewis-microRNA-2 cells were taken
      as MicroRNA transfection group. At the same time, Lewis cells were taken as
      control group and Lewis-EGFP cells as empty plasmid group. The growth curves of
      cells in the three groups were drawn by manual counting method, while the
      invasiveness of cells in the three groups was compared by transmembrane cell
      invasion assay. The three kinds of cells were seeded into BALB/Nude SPF level
      nude mice to detect the formation of tumors and the number of metastases by
      Xenograft experiments. The result showed that the MicroRNA transfection group has
      the lowest vitality of cells proliferation, fewest cells passed through matrigel
      matrix protein layer, and lowest cells invasive rate. Mice with Lewis-microRNA-2
      cells apparently had a longer time of tumor formation. The average tumor mass and
      the number of metastases were significantly lower than the other two groups.
      MicroRNA-2 significantly inhibited Lewis lung cancer cell proliferation, invasion
      and migration in tumor-bearing mice, which may be associated with the regulation
      of target genes PLK1 and TGF-beta. 

PMID- 25064220
TI  - The effects and mechanism of miR-92a and miR-126 on myocardial apoptosis in mouse
      ischemia-reperfusion model.
AB  - Our objective was to explore the effects of miR-92a and miR-126 on myocardial
      apoptosis in mouse ischemia-reperfusion model and further investigate the
      underlying mechanisms. Eighteen Kunming mice were selected and randomly divided
      into sham operation group and ischemia-reperfusion group with nine mice in each
      group. Cardiac muscle tissue was stained with Evans blue to confirm myocardial
      infarction and ischemia. Annexin V/PI double staining was used to detect the
      apoptotic rate of myocardial cells, and terminal-deoxynucleotidyl transferase
      mediated nick end labeling (TUNEL) was used to detect the number of apoptotic
      cells; Western blot was used to detect expression of Caspase 3 to evaluate the
      apoptosis of mouse myocardial cells; qRT-PCR was used to detect expression of miR
      92a and miR-126 in mouse myocardium, and Western blot was used to detect
      expression of HSP70 in two groups. Evans blue staining results showed that there
      was a large area of ischemia in myocardium of ischemia-reperfusion mice with
      marked infarction, suggesting successful establishment of the model. In sham
      operation group, myocardial cells were mostly normal cells. Annexin V/PI double
      staining of flow cytometry result showed that the apoptotic rate was 5.9 % in
      sham operation group and 37.0 % in ischemia-reperfusion group, respectively.
      Apoptosis detection results showed that apoptotic index (AI) of myocardial cells
      in ischemia-reperfusion mice was significantly higher than in sham operation
      group. In addition, qRT-PCR results showed that miR-92a expression in ischemia
      reperfusion group was significantly higher than in sham operation group (F =
      32.302, P = 0.000), and miR-126 expression in ischemia-reperfusion group was
      significantly lower than in sham operation group (F = 41.125, P = 0.000).
      Moreover, HSP70 detected by Western blot showed that HSP expression in ischemia
      reperfusion group was significantly lower than in sham operation group. The
      change of miR-92a was in accordance with AI of myocardial cells. However, the
      change of miR-126 is in contrary with AI of myocardial cells, which may be
      related to the HSP70 expression in myocardial cells.

PMID- 25064218
TI  - Emerging mass spectrometry techniques for the direct analysis of microbial
      colonies.
AB  - One of the emerging areas in microbiology is detecting specialized metabolites
      produced by microbial colonies and communities with mass spectrometry. In this
      review/perspective, we illustrate the emerging mass spectrometry methodologies
      that enable the interrogation of specialized metabolites directly from microbial
      colonies. Mass spectrometry techniques such as imaging mass spectrometry and real
      time mass spectrometry allow two and three-dimensional visualization of the
      distribution of metabolites, often with minimal sample pretreatment. The speed in
      which molecules are captured using these methods requires the development of new
      molecular visualization tools such as molecular networking. Together, these tools
      are beginning to provide unprecedented insight into the chemical world that
      microbes experience. 

PMID- 25064221
TI  - The role of the rs1544410 polymorphism of vitamin D receptor gene in breast
      cancer susceptibility.
AB  - This study was devised to investigate the genetic effect modification of the BsmI
      polymorphism associated with the susceptibility to breast cancer. Case-control
      studies of the BsmI polymorphism and breast cancer were searched. A total of 17
      eligible publications were included in our final analysis. Pooled ORs and 95 %
      CIs were obtained by means of fixed effects model. The general and stratified
      analyses according to ethnicity showed that the association between the BsmI
      polymorphism and the risk of breast cancer was not statistically significant.
      However, the subgroup of the hospital-based studies was found to confer
      protection against the disease (ORBBvs.bb = 0.83, 95 % CI = 0.71-0.97, P h =
      0.571; OR BBvs.Bb+bb = 0.86, 95 % CI = 0.74-1.00, P h = 0.903; OR allele B vs.
      allele b = 0.92, 95 % CI = 0.86-0.99, P h = 0.337). Our results suggested that
      the presence of the BsmI polymorphism may contribute to the susceptibility of
      breast cancer. It is necessary that future large-scale studies should be
      conducted to further confirm the association between the BsmI polymorphism and
      breast cancer risk.

PMID- 25064222
TI  - Effects of high-pressure oxygen therapy on brain tissue water content and AQP4
      expression in rabbits with cerebral hemorrhage.
AB  - To investigate the effects of different atmosphere absolutes (ATA) of high
      pressure oxygen (HPO) on brain tissue water content and Aquaporin-4 (AQP4)
      expression in rabbits with cerebral hemorrhage. 180 New Zealand white rabbits
      were selected and randomly divided into normal group (n = 30), control group (n =
      30) and cerebral hemorrhage group (n = 120), and cerebral hemorrhage group was
      divided into group A, B, C and D with 30 rabbits in each group. The groups
      received 1.0, 1.8, 2.0 and 2.2 ATA of HPO treatments, respectively. Ten rabbits
      in each group were killed at first, third and fifth day to detect the brain
      tissue water content and change of AQP4 expression. In cerebral hemorrhage group,
      brain tissue water content and AQP4 expression after model establishment were
      first increased, then decreased and reached the maximum on third day (p < 0.05).
      Brain tissue water content and AQP4 expression in control group and cerebral
      hemorrhage group were significantly higher than normal group at different time
      points (p < 0.05). In contrast, brain tissue water content and AQP4 expression in
      group C were significantly lower than in group A, group B, group D and control
      group (p < 0.05). In control group, AQP4-positive cells significantly increased
      after model establishment, which reached maximum on third day, and positive cells
      in group C were significantly less than in group A, group B and group D. We also
      found that AQP4 expression were positively correlated with brain tissue water
      content (r = 0.719, p < 0.05) demonstrated by significantly increased AQP4
      expression along with increased brain tissue water content. In conclusion, HPO
      can decrease AQP4 expression in brain tissue of rabbits with cerebral hemorrhage
      to suppress the progression of brain edema and promote repairing of injured
      tissue. 2.0 ATA HPO exerts best effects, which provides an experimental basis for
      ATA selection of HPO in treating cerebral hemorrhage.

PMID- 25064223
TI  - Foxp3 expression in deep rectosigmoid endometriosis lesions and its association
      with chronic pelvic pain.
AB  - Endometriosis is a benign gynecological disease that is related to immune
      response alterations. T regulatory cells modulate immune response, and Foxp3
      seems to be the best marker of these cells. This study evaluated Foxp3 mRNA
      expression in eutopic endometrium from women with endometriosis and healthy
      controls, and its expression in deep rectosigmoid endometriosis lesions, one of
      the more aggressive types of the disease. Foxp3 expression was higher in lesions
      than in eutopic endometrium in the two groups. Moreover, eutopic endometrium
      Foxp3 expression of women with endometriosis was associated with chronic pelvic
      pain and cyclic urinary pain.

PMID- 25064224
TI  - Experience of treating biliary atresia with three types of portoenterostomy at a
      single institution: extended, modified Kasai, and laparoscopic modified Kasai.
AB  - PURPOSE: Generally, open portoenterostomy (PE) involves a wide extended
      anastomosis and all sutures are deep [extended PE (EP)]. In contrast, the
      anastomosis in Kasai's PE (KP), our modified open Kasai PE (MK), and our
      laparoscopic modified Kasai PE (lapMK) involve shallow suturing, especially at
      the 2 and 10 o'clock positions where the right and left bile ducts would be
      normally. We compared outcomes of 36 consecutive biliary atresia (BA) patients
      treated by three types of PE at a single institution during the period 2005-2014;
      EP (n = 13), MK (n = 11), and lapMK (n = 12). METHODS: We compared age at PE,
      time taken to become jaundice-free (total bilirubin <=1.2 mg/dL; JF time),
      proportion of JF subjects [JF ratio (JFR)], steroid dosage, incidence of
      cholangitis, postoperative liver function and CRP, presence of hypersplenism,
      requirement for liver transplantation (LTx), and JF survival with the native
      liver (JF+NL) as indicators of outcome. RESULTS: Patient demographics, steroid
      dosage, JF time, incidence of cholangitis, presence of hypersplenism, operating
      time, blood loss and postoperative biochemistry were similar for all groups.
      However, JFR was significantly higher for lapMK (100 %) versus EP (46.2 %) (p <
      0.05), but not for MK (81.8%) versus EP. Kaplan-Meier analysis showed survival
      with NL was significantly higher for lapMK (10/12: 83.3%: JF in 9; not JF in 1)
      and MK (9/11: 81.8 %: JF in all) versus EP (3/13: 23.1%: JF in all) (p < 0.05,
      respectively), but not for lapMK versus MK. JF+NL in both lapMK (9/12: 75.0%) and
      MK (9/11: 81.8%) were significantly higher compared with EP (3/13: 23.1%) (p <
      0.05, respectively). Intraperitoneal adhesions were less pronounced at LTx in
      lapMK compared with MK or EP. CONCLUSIONS: This study would suggest that depth of
      suturing during PE would appear to influence post-PE outcome. LapMK should be
      reconsidered as a valid treatment option for BA.

PMID- 25064225
TI  - Liver transplantation following the Kasai procedure in treatment of biliary
      atresia: a single institution analysis.
AB  - PURPOSE: This study aimed to assess outcomes of liver transplantation (LTx) in
      patients with biliary atresia (BA). METHODS: The Kasai procedure was performed
      for 358 patients at Tohoku University Hospital between January 1955 and December
      2013; 64 (17.9%) required LTx. These 64 patients were divided into 4 groups
      according to their age at the time of transplantation: Group 1, aged <2 years (n
      = 27); Group 2, aged 2-9 years (n = 16); Group 3, aged 10-19 years (n = 11); and
      Group 4, aged >=20 years (n = 10). Clinical parameters were evaluated
      retrospectively. RESULTS: Both living-donor (n = 57) and deceased-donor (n = 7)
      LTx were performed. Indications were irreversible jaundice (n = 53), intractable
      cholangitis (n = 3), hepatopulmonary syndrome (n = 6), portopulmonary
      hypertension (n = 1), and intestinal bleeding (n = 1). Jaundice occurred more
      frequently in Groups 1 and 2 than in Groups 3 and 4 (p = 0.031). Survival rates
      were 81.5, 100, 90.9, and 80% in Groups 1, 2, 3, and 4, respectively. CONCLUSION:
      Although the overall LTx survival rate was satisfactory, some adult recipients
      experienced LTx-related difficulty. Close follow-up, meticulous assessment of
      physical and social conditions, presence of a multidisciplinary support system,
      and appropriate time course for LTx are all essential factors in the treatment of
      BA.

PMID- 25064226
TI  - Positive C4d staining of the portal vein endothelium in the liver of patients
      with biliary atresia: a role of humoral immunity in ongoing liver fibrosis.
AB  - PURPOSE: This study aimed to clarify the role of complement activation in
      fibrogenesis in BA. METHODS: In total, 27 paraffin-embedded liver biopsy samples
      were immunohistochemically analyzed using C4d polyclonal antibody, vascular cell
      adhesion molecule-1 (VCAM-1), and CD45. The liver samples were obtained from 25
      patients during Kasai operation, and two additional specimens were obtained from
      2 patients by needle biopsy later at the time of liver function deterioration.
      The degree of liver fibrosis was histologically graded 1-3. RESULTS: Among the 25
      samples, 9 showed C4d-positive immunostaining localized on the endothelia of a
      few portal veins in the portal tract. The degree of fibrosis was correlated with
      C4d staining (p = 0.025). The age at Kasai operation correlated with the degree
      of fibrosis and the C4d positivity. Two needle biopsy samples were positive for
      C4d. Among 13 samples submitted for VCAM-1 staining, 2 negative samples were C4d
      negative and all positive C4d samples were VCAM-1 positive with CD45 mononuclear
      cell infiltration. CONCLUSION: These findings suggest that ongoing cirrhosis
      could be a result of progressive "vasculopathy" of the portal vein caused by
      humoral and cell-mediated immune interaction.

PMID- 25064227
TI  - Outcome of partial internal biliary diversion for intractable pruritus in
      children with cholestatic liver disease.
AB  - PURPOSE: Children with cholestatic disorders have undergone liver transplantation
      for intractable pruritus unresponsive to medical therapy even in the absence of
      liver failure. Biliary diversion procedures interrupt the entero-hepatic
      circulation of bile acids allowing them to be excreted in the feces thereby
      lowering the total bile acid pool. We evaluated the outcome of partial internal
      biliary diversion (PIBD) in children with intractable pruritus from inherited
      cholestatic disorders. METHODS: The records of children who underwent PIBD over a
      4-year period were reviewed for etiology of liver disease, demographic data,
      preoperative and postoperative biochemical profile and improvement of pruritus.
      Standard statistical methods were used for analysis. RESULTS: Of the 12 children,
      10 had progressive familial intrahepatic cholestasis (PFIC) and 2 had Alagille
      syndrome (AS). PIBD was done using an isolated jejunal loop as a conduit from
      gall bladder to mid ascending colon. Median period of follow up was 30 months.
      Pruritus resolved in nine children with significant reduction of serum bile acids
      (P < 0.02). CONCLUSION: To our knowledge, this is the largest reported series of
      children with PIBD. PIBD is a safe, well-tolerated and effective alternative to
      liver transplant in children with PFIC and AS who have intractable pruritus in
      the absence of synthetic liver failure.

PMID- 25064228
TI  - Histological features of primary tumors after induction or high-dose chemotherapy
      in high-risk neuroblastoma.
AB  - PURPOSE: In the recent years in Japan, an increasing number of patients with
      neuroblastoma (NB) are being treated by the "delayed local treatment (DL)"
      policy, undergoing surgery after the completion of high-dose chemotherapy with
      hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings
      of second-look operations, including those of patients treated with DL. PATIENTS:
      From 1998 to 2013, 26 patients with high-risk NB underwent radical operation
      following chemotherapy. Surgery was performed after induction chemotherapy in 17
      cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC
      before undergoing tumor resection (DL). The amount of necrosis and the degree of
      differentiation within the post-treatment tumor were assessed. RESULTS: Eighty
      eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two
      DL cases showed complete disappearance of viable tumor cells. Amount of necrosis
      did not affect the prognosis of the patient. Tumors with immature, poorly
      differentiated phenotypes showed an extremely aggressive thereafter. Though not
      statistically proven, (123)I-MIBG (metaiodobenzylguanidine) uptake may be
      correlated with the amount of viable cells remaining within the tumor, but not
      with the degree of differentiation. CONCLUSIONS: Our results support the previous
      reports advocating that tumors that sustain unfavorable histology after
      chemotherapy behave aggressively thereafter.

PMID- 25064229
TI  - Comparison between closed and open techniques for creating a retroperitoneal
      space for retroperitoneoscopic renal surgery in children.
AB  - AIM: During retroperitoneoscopic renal surgery (RPRS), the open technique (OT)
      for trocar insertion is always associated with CO2 leakage around the first
      trocar, while the closed technique (CT) involves advancing an optical trocar into
      the retroperitoneal space (RS) under direct vision. We are the first to compare
      OT with CT. METHODS: Forty-one cases of RPRS performed for pyeloplasty (31), hemi
      nephrectomy (4), nephrectomy (4), stone removal (1), and cyst excision (1) were
      studied. The initial 5 mm trocar was inserted using OT (n = 11) or CT (n = 30).
      The tip of a telescope was used for blunt dissection of the retroperitoneum to
      create the RS. RESULTS: Ages and weights at RPRS were similar (OT versus CT: 7.3
      versus 7.1 years; 25.4 versus 25.0 kg; respectively). In CT, RS access was
      significantly faster (38.2 versus 5.6 min), RS was created significantly quicker
      (77.7 versus 31.9 min), and narcotic usage was significantly less (4.0 versus 1.5
      days). In OT, CO2 leaked in 11/11 and the retroperitoneum was torn in 3/11. In CT
      there was no leakage and no tearing. CONCLUSIONS: CT is quicker and safer than OT
      during RPRS.

PMID- 25064230
TI  - Balloon tracheoplasty as initial treatment for neonates with symptomatic
      congenital tracheal stenosis.
AB  - Neonates with congenital tracheal stenosis (CTS) sometimes develop respiratory
      distress and may be difficult to intubate. We used balloon tracheoplasty with a
      rigid bronchoscope for emergency airway management in neonates with symptomatic
      CTS. Herein, we describe the balloon tracheoplasty procedure and the early
      outcomes following its use as the initial treatment of neonatal symptomatic CTS.
      We performed a retrospective analysis of five neonates with CTS who were
      initially treated with balloon tracheoplasty at our institution from January 2010
      to December 2013. Five patients with a mean birthweight of 2,117 g were treated
      during the study period. Of these, four developed respiratory distress after
      birth, and all patients had difficult intubations. In all five patients,
      definitive diagnosis of CTS was made by rigid bronchoscopy and 3-dimensional
      reconstruction scan. A total of nine balloon dilatations were performed in five
      patients. Following balloon tracheoplasty, two patients were extubated, one was
      extubated after resection and end-to-end anastomosis following initial balloon
      dilatation, and one remained hospitalized with tracheostomy for tracheomalacia.
      The remaining patient died from tracheal bleeding associated with congenital
      heart disease. Although our sample size was small, balloon tracheoplasty is a
      potentially effective initial treatment for selected cases with neonatal
      symptomatic CTS. 

PMID- 25064232
TI  - Realization of dynamic thermal emission control.
AB  - Thermal emission in the infrared range is important in various fields of
      research, including chemistry, medicine and atmospheric science. Recently, the
      possibility of controlling thermal emission based on wavelength-scale optical
      structures has been intensively investigated with a view towards a new generation
      of thermal emission devices. However, all demonstrations so far have involved the
      'static' control of thermal emission; high-speed modulation of thermal emission
      has proved difficult to achieve because the intensity of thermal emission from an
      object is usually determined by its temperature, and the frequency of temperature
      modulation is limited to 10-100 Hz even when the thermal mass of the object is
      small. Here, we experimentally demonstrate the dynamic control of thermal
      emission via the control of emissivity (absorptivity), at a speed four orders of
      magnitude faster than is possible using the conventional temperature-modulation
      method. Our approach is based on the dynamic control of intersubband absorption
      in n-type quantum wells, which is enhanced by an optical resonant mode in a
      photonic crystal slab. The extraction of electrical carriers from the quantum
      wells leads to an immediate change in emissivity from 0.74 to 0.24 at the
      resonant wavelength while maintaining much lower emissivity at all other
      wavelengths. 

PMID- 25064231
TI  - Surface-initiated self-healing of polymers in aqueous media.
AB  - Polymeric materials that intrinsically heal at damage sites under wet or moist
      conditions are urgently needed for biomedical and environmental applications.
      Although hydrogels with self-mending properties have been engineered by means of
      mussel-inspired metal-chelating catechol-functionalized polymer networks,
      biological self-healing in wet conditions, as occurs in self-assembled holdfast
      proteins in mussels and other marine organisms, is generally thought to involve
      more than reversible metal chelates. Here we demonstrate self-mending in metal
      free water of synthetic polyacrylate and polymethacrylate materials that are
      surface-functionalized with mussel-inspired catechols. Wet self-mending of
      scission in these polymers is initiated and accelerated by hydrogen bonding
      between interfacial catechol moieties, and consolidated by the recruitment of
      other non-covalent interactions contributed by subsurface moieties. The repaired
      and pristine samples show similar mechanical properties, suggesting that the
      triggering of complete self-healing is enabled underwater by the formation of
      extensive catechol-mediated interfacial hydrogen bonds. 

PMID- 25064233
TI  - Improving the quality of life of multiple sclerosis patients through coping
      strategies in routine medical practice.
AB  - Multiple sclerosis (MS) has a major impact on quality of life (QoL). Coping
      strategies which may influence QoL have not been identified. Furthermore, there
      is no coping scale designed to measure coping in MS patients and concise enough
      for routine medical practice. We used 46 items and 7 coping dimensions; we
      successively reduced the minimum number of dimensions through confirmatory factor
      analysis (CFA) and Rasch modelling. The resulting scale was submitted to
      psychometric validation via an independent cross-sectional analysis. After
      administration to 331 MS patients, we eliminated 10 of the 46 initial items; a
      CFA iterative algorithm identified a positive coping (PC) group and a negative
      coping (NC) group; an iterative reduction algorithm led to a final 10 items
      questionnaire, which was tested in an independent, new cross-sectional sample of
      457 patients. Psychometric tests, including the Rasch model and CFA, successfully
      validated the scale, confirming the two dimensions and the absence of
      differential item functioning. The correlation between coping and QoL increased
      to 0.59 and 0.62 for NC and PC, respectively, compared with 0.33 found with
      existing scales. Our findings justify a one-dimensional overall coping scale (PC
      + NC). The effect of coping on QoL can be evaluated simply by adding together a
      positive and a negative coping strategy, for which we developed a short 10-item
      scale, which can be considered as an effective means of measuring the impact of
      coping on QoL and is ideal in routine medical practice. 

PMID- 25064234
TI  - Wavelet-based algorithm to the evaluation of contrasted hepatocellular carcinoma
      in CT-images after transarterial chemoembolization.
AB  - BACKGROUND: Hepatocellular carcinoma is a primary tumor of the liver and involves
      different treatment modalities according to the tumor stage. After local
      therapies, the tumor evaluation is based on the mRECIST criteria, which involves
      the measurement of the maximum diameter of the viable lesion. This paper
      describes a computed methodology to measure through the contrasted area of the
      lesions the maximum diameter of the tumor by a computational algorithm. METHODS:
      63 computed tomography (CT) slices from 23 patients were assessed. Non-contrasted
      liver and HCC typical nodules were evaluated, and a virtual phantom was developed
      for this purpose. Optimization of the algorithm detection and quantification was
      made using the virtual phantom. After that, we compared the algorithm findings of
      maximum diameter of the target lesions against radiologist measures. RESULTS:
      Computed results of the maximum diameter are in good agreement with the results
      obtained by radiologist evaluation, indicating that the algorithm was able to
      detect properly the tumor limits. A comparison of the estimated maximum diameter
      by radiologist versus the algorithm revealed differences on the order of 0.25 cm
      for large-sized tumors (diameter > 5 cm), whereas agreement lesser than 1.0 cm
      was found for small-sized tumors. CONCLUSIONS: Differences between algorithm and
      radiologist measures were accurate for small-sized tumors with a trend to a small
      decrease for tumors greater than 5 cm. Therefore, traditional methods for
      measuring lesion diameter should be complemented non-subjective measurement
      methods, which would allow a more correct evaluation of the contrast-enhanced
      areas of HCC according to the mRECIST criteria.

PMID- 25064235
TI  - Early pregnancy metabolite profiling discovers a potential biomarker for the
      subsequent development of gestational diabetes mellitus.
AB  - Current early pregnancy screening tools to identify women at risk of developing
      gestational diabetes mellitus lack both specificity and sensitivity. As a result,
      the foetus and mother are often subjected to insult during disease progression,
      prior to diagnosis and treatment in later pregnancy. Metabolomics is an
      analytical approach, which allows for appraisal of small molecular mass compounds
      in a biofluid. The aim of this pilot study was to investigate the relationship
      between the early gestation serum metabolite profile and the subsequent
      development of gestational diabetes mellitus in the search for early pregnancy
      biomarkers and potential metabolic mechanisms. Our nested case-control study
      analysed maternal serum at 20 weeks' gestation, obtained from the New Zealand
      cohort of the Screening for Pregnancy Endpoints study. Metabolomic profiling was
      performed using gas chromatography coupled to mass spectrometry, and metabolites
      were identified using R software and an in-house mass spectral library.
      Statistical analysis was performed using SPSS version 21.0. Forty-eight
      metabolites were identified in the serum samples. Itaconic acid (P = 0.0003),
      with a false discovery rate of 0.012, was found to be significantly more abundant
      in women who subsequently developed gestational diabetes mellitus, when compared
      to controls with uncomplicated pregnancies. The current pilot study found that
      itaconic acid may have potential as a novel biomarker in early pregnancy to
      predict the subsequent development of gestational diabetes mellitus. However, the
      findings from this pilot study require validation with a larger, diverse
      population before translation into the clinical setting.

PMID- 25064236
TI  - The histidine-rich glycoprotein A1042G polymorphism and recurrent miscarriage: a
      pilot study.
AB  - BACKGROUND: Histidine-rich glycoprotein (HRG) has previously been shown to have
      an impact on implantation and fertility. The aim of this study was to investigate
      if there is an association between the HRG A1042G single nucleotide polymorphism
      (SNP) and recurrent miscarriage. METHODS: The study was designed as a case
      control study and the women were included at University Hospitals in Sweden. 186
      cases with recurrent miscarriage were compared with 380 pregnant controls with no
      history of miscarriage. Each woman was genotyped for the HRG A1042G SNP. RESULTS:
      The results indicated that the frequency of heterozygous HRG A1042G carriers was
      higher among controls compared to cases (34.7% vs 26.3%; p<0.05). In a bivariate
      regression analysis, a negative association was found between recurrent
      miscarriage and heterozygous A/G carriers both in the entire study population (OR
      0.67, 95% CI 0.45 - 0.99; p<0.05) as well as in a subgroup of women with primary
      recurrent miscarriage (OR 0.37, 95% CI 0.16 - 0.84; p<0.05). These results
      remained even after adjustment for known confounders such as age, BMI and thyroid
      disease (OR 0.36, 95% CI 0.15 - 0.84; p<0.05). CONCLUSIONS: Women who are
      heterozygous carriers of the HRG A1042G SNP suffer from recurrent miscarriage
      more seldom than homozygous carriers. Thus, analysis of the HRG A1042G SNP might
      be of importance for individual counseling regarding miscarriage.

PMID- 25064237
TI  - Statistical comparison of the slopes of two regression lines: A tutorial.
AB  - Comparing the slopes of two regression lines is an almost daily task in
      analytical laboratories. The usual procedure is based on a Student's t-test
      although literature differs in whether the standard errors of the slopes or the
      standard errors of the regressions should be employed to get a pooled standard
      error. In this work fundamental concepts on the use of the Student's test were
      reviewed and Monte Carlo simulations were done to ascertain whether relevant
      differences arise when the two options are considered. It was concluded that for
      small sample sets (as it is usual in analytical laboratories) the Student's t
      test based on the standard error of regression models must be used and special
      attention must be paid on the equality of the models variances. Finally,
      alternative approaches were reviewed, with emphasis on a simple one based on the
      analysis of the covariance (ANCOVA). 

PMID- 25064238
TI  - Determination of total mercury in nuts at ultratrace level.
AB  - Total mercury, at MUg kg(-1) level, was determined in different types of nuts
      (cashew nut, Brazil nuts, almond, pistachio, peanut, walnut) using a direct
      mercury analyser after previous sample defatting and by cold vapour atomic
      fluorescence spectrometry. There is not enough sensitivity in the second approach
      to determine Hg in previously digested samples due to the strong matrix effect.
      Mercury levels in 25 edible nut samples from Brazil and Spain were found in the
      range from 0.6 to 2.7MUg kg(-1) by using the pyrolysis of sample after the
      extraction of the nut fat. The accuracy of the proposed method was confirmed by
      analysing certified reference materials of Coal Fly Ash-NIST SRM 1633b, Fucus
      IAEA 140 and three unpolished Rice Flour NIES-10. The observed results were in
      good agreement with the certified values. The recoveries of different amounts of
      mercury added to nut samples ranged from 94 to 101%. RSD values corresponding to
      three measurements varied between 2.0 and 14% and the limit of detection and
      quantification of the method were 0.08 and 0.3MUg kg(-1), respectively.

PMID- 25064239
TI  - Local classification: Locally weighted-partial least squares-discriminant
      analysis (LW-PLS-DA).
AB  - The possibility of devising a simple, flexible and accurate non-linear
      classification method, by extending the locally weighted partial least squares
      (LW-PLS) approach to the cases where the algorithm is used in a discriminant way
      (partial least squares discriminant analysis, PLS-DA), is presented. In
      particular, to assess which category an unknown sample belongs to, the proposed
      algorithm operates by identifying which training objects are most similar to the
      one to be predicted and building a PLS-DA model using these calibration samples
      only. Moreover, the influence of the selected training samples on the local model
      can be further modulated by adopting a not uniform distance-based weighting
      scheme which allows the farthest calibration objects to have less impact than the
      closest ones. The performances of the proposed locally weighted-partial least
      squares-discriminant analysis (LW-PLS-DA) algorithm have been tested on three
      simulated data sets characterized by a varying degree of non-linearity: in all
      cases, a classification accuracy higher than 99% on external validation samples
      was achieved. Moreover, when also applied to a real data set (classification of
      rice varieties), characterized by a high extent of non-linearity, the proposed
      method provided an average correct classification rate of about 93% on the test
      set. By the preliminary results, showed in this paper, the performances of the
      proposed LW-PLS-DA approach have proved to be comparable and in some cases better
      than those obtained by other non-linear methods (k nearest neighbors, kernel-PLS
      DA and, in the case of rice, counterpropagation neural networks). 

PMID- 25064240
TI  - A new method to assay hypoxia-inducible factor-1 based on small molecule binding
      DNA.
AB  - Hypoxia-inducible factor-1 (HIF-1) is among the most important indicators of
      hypoxia in evaluating severity of many diseases. In this work, a novel method for
      HIF-1 detection is proposed by using electrochemical techniques based on small
      molecule binding DNA. In this method, since the designed DNA sequence can
      specifically bind with either an electroactive small molecule or HIF-1, the
      signal readout is inversely proportional to HIF-1 concentration, thus a simple
      and easily-operated method for HIF-1 detection can be developed. With the
      proposed method, HIF-1 can be determined in a linear range from 5 to 25nM with a
      detection limit of 2.8nM. Furthermore, the proposed method can be directly used
      to assay HIF-1 in placenta tissue, and the assay results can reliably reflect the
      severity of preeclampsia, a very dangerous condition during pregnancy. The
      proposed method also shows desirable sensitivity, high selectivity and excellent
      reproducibility, so this method can have potential applications in clinical
      practice. 

PMID- 25064242
TI  - Liquid extraction surface analysis in-line coupled with capillary electrophoresis
      for direct analysis of a solid surface sample.
AB  - A surface-sampling technique of liquid extraction surface analysis (LESA) was in
      line coupled with capillary electrophoresis (CE) to expand the specimen types for
      CE to solid surfaces. The new direct surface analysis method of LESA-CE was
      applied to the determination of organophosphorus pesticides, including
      glufosinate-ammonium, aminomethylphosphonic acid, and glyphosate on the external
      surface of a fruit such as apple. Without any sample pretreatment, the analytes
      sprayed on the surface of a half apple were directly extracted into a liquid
      microjunction formed by dispensing the extractant from the inlet tip of a
      separation capillary. After extraction, the analytes were derivatized in
      capillary with a fluorophore 4-fluoro-7-nitro-2,1,3-benzoxadiazole and analyzed
      with CE-laser induced fluorescence (LIF). The limits of detection for glufosinate
      ammonium, aminomethylphosphonic acid, and glyphosate were 2.5, 1, and 10ppb,
      respectively, which are at least 20 times lower than the tolerance limits
      established by the U.S. Environmental Protection Agency. Thus, we demonstrated
      that LESA-CE is a quite sensitive and convenient method to determine analytes on
      a solid surface avoiding the dilution from sample pretreatment procedures
      including homogenization of a bulk sample. 

PMID- 25064241
TI  - Amperometric magnetoimmunoassay for the direct detection of tumor necrosis factor
      alpha biomarker in human serum.
AB  - An amperometric immunoassay for the determination of tumor necrosis factor alpha
      (TNFalpha) protein biomarker in human serum based on the use of magnetic
      microbeads (MBs) and disposable screen-printed carbon electrodes (SPCEs) has been
      developed. The specifically modified microbeads were magnetically captured on the
      working electrode surface and the amperometric responses were measured at -0.20V
      (vs. Ag pseudo-reference electrode), upon addition of hydroquinone (HQ) as
      electron transfer mediator and H2O2 as the enzyme substrate. After a thorough
      optimization of the assay, extremely low limits of detection were achieved: 2.0pg
      mL(-1) (36fM) and 5.8pg mL(-1) (105fM) for standard solutions and spiked human
      serum, respectively. The simplicity, robustness and this clinically interesting
      LOD proved the developed TNFalpha immunoassay as a good contender for real
      clinical application.

PMID- 25064243
TI  - Solvent selection in ultrasonic-assisted emulsification microextraction:
      Comparison between high- and low-density solvents by means of novel type of
      extraction vessel.
AB  - There are numerous published reports about dispersive liquid phase
      microextraction of the wide range of substances, however, till now no broadly
      accepted systematic and purpose oriented selection of extraction solvent has been
      proposed. Most works deal with the optimization of available solvents without
      adequate pre-consideration of properness. In this study, it is tried to compare
      the performances of low- and high-density solvents at the same conditions by
      means of novel type of extraction vessel with head and bottom conical shape.
      Extraction efficiencies of seven basic pharmaceutical compounds using eighteen
      common organic solvents were studied in this work. It was much easier to work
      with high-density solvents and they mostly showed better performances. This work
      shows that although exact predicting the performance of the solvents is
      multifaceted case but the pre-consideration of initial selection of solvents with
      attention to the physiochemical properties of the desired analytes is feasible
      and promising. Finally, the practicality of the method for extraction from urine
      and plasma samples was investigated. 

PMID- 25064244
TI  - Three-dimensional printed sample load/inject valves enabling online monitoring of
      extracellular calcium and zinc ions in living rat brains.
AB  - We have developed a simple and low-cost flow injection system coupled to a
      quadruple ICP-MS for the direct and continuous determination of multi-element in
      microdialysates. To interface microdialysis sampling to an inductively coupled
      plasma mass spectrometer (ICP-MS), we employed 3D printing to manufacture an as
      designed sample load/inject valve featuring an in-valve sample loop for precise
      handling of microliter samples with a dissolved solids content of 0.9% NaCl
      (w/v). To demonstrate the practicality of our developed on-line system, we
      applied the 3D printed valve equipped a 5-MUL sample loop to minimize the
      occurrence of salt matrix effects and facilitate an online dynamic monitoring of
      extracellular calcium and zinc ions in living rat brains. Under the practical
      condition (temporal resolution: 10h(-1)), dynamic profiling of these two metal
      ions in living rat brain extracellular fluid after probe implantation (the basal
      values for Ca and Zn were 12.11+/-0.10mg L(-1) and 1.87+/-0.05MUg L(-1),
      respectively) and real-time monitoring of the physiological response to
      excitotoxic stress elicited upon perfusing a solution of 2.5mM N-methyl-d
      aspartate were performed.

PMID- 25064245
TI  - Numerical modeling of surface reaction kinetics in electrokinetically actuated
      microfluidic devices.
AB  - We outline a comprehensive numerical procedure for modeling of species transport
      and surface reaction kinetics in electrokinetically actuated microfluidic devices
      of rectangular cross section. Our results confirm the findings of previous
      simplified approaches that a concentration wave is created for sufficiently long
      microreactors. An analytical solution, developed for the wave propagation speed,
      shows that, when normalizing with the fluid mean velocity, it becomes a function
      of three parameters comprising the channel aspect ratio, the relative adsorption
      capacity, and the kinetic equilibrium constant. Our studies also reveal that the
      reactor geometry idealized as a slit, instead of a rectangular shape, gives rise
      to the underestimation of the saturation time. The extent of this underestimation
      increases by increasing the Damkohler number or decreasing the dimensionless
      Debye-Huckel parameter. Moreover, increasing the values of the Damkohler number,
      the dimensionless Debye-Huckel parameter, the relative adsorption capacity, and
      the velocity scale ratio results in lower saturation times. 

PMID- 25064246
TI  - Validation of a qualitative screening method for pesticides in fruits and
      vegetables by gas chromatography quadrupole-time of flight mass spectrometry with
      atmospheric pressure chemical ionization.
AB  - A wide-scope screening method was developed for the detection of pesticides in
      fruit and vegetables. The method was based on gas chromatography coupled to a
      hybrid quadrupole time-of-flight mass spectrometer with an atmospheric pressure
      chemical ionization source (GC-(APCI)QTOF MS). A non-target acquisition was
      performed through two alternating scan events: one at low collision energy and
      another at a higher collision energy ramp (MS(E)). In this way, both protonated
      molecule and/or molecular ion together with fragment ions were obtained in a
      single run. Validation was performed according to SANCO/12571/2013 by analysing
      20 samples (10 different commodities in duplicate), fortified with a test set of
      132 pesticides at 0.01, 0.05 and 0.20mg kg(-1). For screening, the detection was
      based on one diagnostic ion (in most cases the protonated molecule). Overall, at
      the 0.01mg kg(-1) level, 89% of the 2620 fortifications made were detected. The
      screening detection limit for individual pesticides was 0.01mg kg(-1) for 77% of
      the pesticides investigated. The possibilities for identification according to
      the SANCO criteria, requiring two ions with a mass accuracy <=+/-5ppm and an ion
      ratio deviation <=+/-30%, were investigated. At the 0.01mg kg(-1) level,
      identification was possible for 70% of the pesticides detected during screening.
      This increased to 87% and 93% at the 0.05 and 0.20mg kg(-1) level, respectively.
      Insufficient sensitivity for the second ion was the main reason for the inability
      to identify detected pesticides, followed by deviations in mass accuracy and ion
      ratios.

PMID- 25064247
TI  - High-throughput analysis by SP-LDI-MS for fast identification of adulterations in
      commercial balsamic vinegars.
AB  - Balsamic vinegar (BV) is a typical and valuable Italian product, worldwide
      appreciated thanks to its characteristic flavors and potential health benefits.
      Several studies have been conducted to assess physicochemical and microbial
      compositions of BV, as well as its beneficial properties. Due to highly
      disseminated claims of antioxidant, antihypertensive and antiglycemic properties,
      BV is a known target for frauds and adulterations. For that matter, product
      authentication, certifying its origin (region or country) and thus the processing
      conditions, is becoming a growing concern. Striving for fraud reduction as well
      as quality and safety assurance, reliable analytical strategies to rapidly
      evaluate BV quality are very interesting, also from an economical point of view.
      This work employs silica plate laser desorption/ionization mass spectrometry (SP
      LDI-MS) for fast chemical profiling of commercial BV samples with protected
      geographical indication (PGI) and identification of its adulterated samples with
      low-priced vinegars, namely apple, alcohol and red/white wines. 

PMID- 25064248
TI  - A new measure of orthogonality for multi-dimensional chromatography.
AB  - Multi-dimensional chromatographic techniques, such as (comprehensive) two
      dimensional liquid chromatography and (comprehensive) two-dimensional gas
      chromatography, are increasingly popular for the analysis of complex samples,
      such as protein digests or mineral oils. The reason behind the popularity of
      these techniques is the superior performance, in terms of peak-production rate
      (peak capacity per unit time), that multi-dimensional separations offer compared
      to their one-dimensional counterparts. However, to fully utilize the potential of
      multi-dimensional chromatography it is essential that the separation mechanisms
      used in each dimension be independent of each other. In other words, the two
      separation mechanisms need to be orthogonal. A number of algorithms have been
      proposed in the literature for measuring chromatographic orthogonality. However,
      these methods have their limitations, such as reliance on the division of the
      separation space into bins, need for specialist software or requirement of
      advanced programming skills. In addition, some of the existing methods for
      measuring orthogonality include regions of the separation space that do not
      feature peaks. In this paper we introduce a number of equations which provides
      information on the spread of the peaks within the separation space in addition to
      measuring orthogonality, without the need for complex computations or division of
      the separation space into bins. 

PMID- 25064249
TI  - Voltage mapping for delineating inexcitable dense scar in patients undergoing
      atrial fibrillation ablation: a new end point for enhancing pulmonary vein
      isolation.
AB  - BACKGROUND: Characterization of left atrial scar using bipolar voltage (BiV)
      mapping is not well defined. We have previously shown that the BiV range of 0.2
      0.45 mV can identify chronic scar from prior pulmonary vein isolation (PVI).
      OBJECTIVE: This study sought to determine a BiV range that can identify atrial
      inexcitable dense scar (IDS) in patients acutely and chronically after PVI.
      METHODS: Thirty consecutive patients undergoing first time (n = 15) or redo (n =
      15) PVI were included. A left atrial shell was created using electroanatomic
      mapping, and IDS was defined by inability to capture at an output of 10 mA and a
      pulse width of 2 ms in sinus rhythm, circumferentially at the edge of PVI-related
      scar (<=5 mm). At each pacing site, BiV amplitude and atrial capture were
      recorded. RESULTS: Overall, 837 pacing sites were assessed. BiV predicted IDS
      (receiver operating characteristic curve area 0.93 for first time PVI and 0.90
      for redo PVI). In first time PVI, the best BiV value to predict IDS was 0.45 mV
      for the left pulmonary vein-left atrial appendage (LAA-LPV) ridge (sensitivity
      0.98; specificity 1.0) and 0.2 mV for other localizations (sensitivity 0.91;
      specificity 0.86). In redo PVI, the best BiV value to predict IDS was 0.2 mV for
      the LAA-LPV ridge (sensitivity 0.77; specificity 1.0) and 0.15 mV for other
      localizations (sensitivity 0.81; specificity 0.82). CONCLUSION: BiV reproducibly
      identifies acute and chronic IDS using a cutoff value of 0.2 mV (0.45 mV for the
      LAA-LPV ridge) in patients undergoing first time PVI and 0.15 mV (0.2 mV for the
      LAA-LPV ridge) in patients undergoing redo PVI. IDS thus identified may be a
      rigorous tool for validating PVI.

PMID- 25064250
TI  - Adapting the coping in deliberation (CODE) framework: a multi-method approach in
      the context of familial ovarian cancer risk management.
AB  - OBJECTIVE: To test whether the coping in deliberation (CODE) framework can be
      adapted to a specific preference-sensitive medical decision: risk-reducing
      bilateral salpingo-oophorectomy (RRSO) in women at increased risk of ovarian
      cancer. METHODS: We performed a systematic literature search to identify issues
      important to women during deliberations about RRSO. Three focus groups with
      patients (most were pre-menopausal and untested for genetic mutations) and 11
      interviews with health professionals were conducted to determine which issues
      mattered in the UK context. Data were used to adapt the generic CODE framework.
      RESULTS: The literature search yielded 49 relevant studies, which highlighted
      various issues and coping options important during deliberations, including
      mutation status, risks of surgery, family obligations, physician recommendation,
      peer support and reliable information sources. Consultations with UK stakeholders
      confirmed most of these factors as pertinent influences on deliberations.
      Questions in the generic framework were adapted to reflect the issues and coping
      options identified. CONCLUSIONS: The generic CODE framework was readily adapted
      to a specific preference-sensitive medical decision, showing that deliberations
      and coping are linked during deliberations about RRSO. PRACTICE IMPLICATIONS:
      Adapted versions of the CODE framework may be used to develop tailored decision
      support methods and materials in order to improve patient-centred care.

PMID- 25064251
TI  - Matching metabolites and reactions in different metabolic networks.
AB  - Comparing and identifying matching metabolites, reactions, and compartments in
      genome-scale reconstructed metabolic networks can be difficult due to
      inconsistent naming in different networks. In this paper, we propose metabolite
      and reaction matching techniques for matching metabolites and reactions in a
      given metabolic network to metabolites and reactions in another metabolic
      network. We employ a variety of techniques that include approximate string
      matching, similarity score functions and multi-step filtering techniques, all
      enhanced by a set of rules based on the underlying metabolic biochemistry. The
      proposed techniques are evaluated by an empirical study on four pairs of
      metabolic networks, and significant accuracy gains are achieved using the
      proposed metabolite and reaction identification techniques. 

PMID- 25064252
TI  - Proteomic characterization of nitrated cell targets after hypobaric hypoxia and
      reoxygenation in rat brain.
AB  - This study analyzes the nitrated protein profile of the rat-brain cortex in a
      model of hypoxia/reoxygenation, identifying the nitrated proteins and assessing
      spot changes. The proteins identified were grouped into categories, according to
      their function: 1) metabolism: pyruvate kinase (PK), alpha-enolase,
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH), phosphoglycerate mutase 1
      (PGAM1), and glutamine synthetase (GS); 2) cytoskeletal proteins: alpha-tubulin,
      beta-tubulin, gamma-actin, and glial fibrillary acidic protein (GFAP); 3)
      chaperones: heat-shock protein 71kDa (HSP71); and 4) carrier proteins: voltage
      dependent anion-selective channel protein 1 (VDAC-1) and Atp6v1a. PK, alpha
      enolase, and GS nitration rates were upregulated, increasing progressively during
      reoxygenation and peaking at 24h. GAPDH and PGAM1 nitration levels fell after
      hypoxia/reoxygenation. alpha-Tubulin, beta-tubulin, gamma-actin, and GFAP
      nitration rates augmented at 24h, but diminished at 5d. HSP71 suffered from
      nitration immediately after hypoxia, but not during reoxygenation. VDAC-1
      tyrosine nitration was identified only in the control group, whereas detectable
      Atp6v1a nitration levels were observed only immediately after hypoxia. The data
      have been deposited to the ProteomeXchange with identifier PXD001049. Our
      findings suggest a hypothetically crucial linkage between nitration-related
      protein modifications and metabolic and cell-structure alterations. These changes
      are probably needed for the remodeling and plasticity processes activated by the
      hypoxic brain response. BIOLOGICAL SIGNIFICANCE: For the first time the spectrum
      of nitrated proteins in the hypoxic brain as well as its changes during
      reoxygenation are described. Our findings suggest a hypothetically crucial
      linkage between nitration-related protein modifications and metabolic and cell
      structure alterations. These changes are probably needed for the remodeling and
      plasticity processes activated by the hypoxic brain response. The biological
      relevance of these findings is linked to the important role developed by the
      signaling molecule NO in the hypoxic brain, and could be interpreted in two
      different but complementary ways: first, as a mechanism of damage due to
      nitration impacts over some key proteins affecting its structure and function;
      and second, as a regulation mechanism involved in the hypoxic response. Hence,
      based on the modified proteins identified and their functions, it would be
      possible to design new tools and therapies to prevent brain damage in low-oxygen
      pressure atmospheres.

PMID- 25064253
TI  - Mueller-Weiss syndrome: imaging and implications.
AB  - Mueller-Weiss syndrome (MWS), or spontaneous osteonecrosis of the tarsal
      navicular in adults, is a rare cause of chronic medial midfoot pain. MWS has been
      described in orthopedic, podiatric, and radiologic literature without consensus
      agreement on its pathophysiology and treatment. We present the radiographic and
      magnetic resonance imaging of a case of MWS with reference to navicular
      biomechanical stressors and potential pathogenesis. 

PMID- 25064254
TI  - Resistance to the crayfish plague pathogen, Aphanomyces astaci, in two freshwater
      shrimps.
AB  - Aphanomyces astaci, the causal agent of the crayfish plague, has recently been
      confirmed to infect also freshwater-inhabiting crabs. We experimentally tested
      the resistance of freshwater shrimps, another important decapod group inhabiting
      freshwaters, to this pathogen. We exposed individuals of two Asian shrimp
      species, Macrobrachium dayanum and Neocaridina davidi, to zoospores of the
      pathogen strain isolated from Procambarus clarkii, a known A. astaci carrier
      likely to get into contact with shrimps. The shrimps were kept in separate
      vessels up to seven weeks; exuviae and randomly chosen individuals were sampled
      throughout the experiment. Shrimp bodies and exuviae were tested for A. astaci
      presence by a species-specific quantitative PCR. The results were compared with
      amounts of A. astaci DNA in an inert substrate to distinguish potential pathogen
      growth in live specimens from persisting spores or environmental DNA attached to
      their surface. In contrast to susceptible crayfish Astacus astacus, we did not
      observe mortality of shrimps. The amount of detected pathogen DNA was decreasing
      steadily in the inert substrate, but it was still detectable several weeks after
      zoospore addition, which should be considered in studies relying on molecular
      detection of A. astaci. Probably due to moulting, the amount of A. astaci DNA was
      decreasing in N. davidi even faster than in the inert substrate. In contrast,
      high pathogen DNA levels were detected in some non-moulting individuals of M.
      dayanum, suggesting that A. astaci growth may be possible in tissues of this
      species. Further experiments are needed to test for the potential of long-term A.
      astaci persistence in freshwater shrimp populations. 

PMID- 25064255
TI  - Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a
      from Malaysian Bungarus fasciatus venom.
AB  - Presynaptic neurotoxins are one of the major components in Bungarus venom. Unlike
      other Bungarus species that have been studied, beta-bungarotoxin has never been
      isolated from Bungarus fasciatus venom. It was hypothesized that the absence of
      beta-bungarotoxin in this species was due to divergence during evolution prior to
      evolution of beta-bungarotoxin. In this study, we have isolated a beta
      bungarotoxin isoform we named P-elapitoxin-Bf1a by using gel filtration, cation
      exchange and reverse-phase chromatography from Malaysian B. fasciatus venom. The
      toxin consists of two heterogeneous subunits, subunit A and subunit B. LCMS/MS
      data showed that subunit A was homologous to acidic phospholipase A2 subunit A3
      from Bungarus candidus and B. multicinctus venoms, whereas subunit B was
      homologous with subunit B1 from B. fasciatus venom that was previously detected
      by cDNA cloning. The toxin showed concentration- and time-dependent reduction of
      indirect-twitches without affecting contractile responses to ACh, CCh or KCl at
      the end of experiment in the chick biventer preparation. Toxin modification with
      4-BPB inhibited the neurotoxic effect suggesting the importance of His-48. Tissue
      pre-incubation with monovalent B. fasciatus (BFAV) or neuro-polyvalent antivenom
      (NPV), at the recommended titer, was unable to inhibit the twitch reduction
      induced by the toxin. This study indicates that Malaysian B. fasciatus venom has
      a unique beta-bungarotoxin isoform which was not neutralized by antivenoms. This
      suggests that there might be other presynaptic neurotoxins present in the venom
      and there is a variation in the enzymatic neurotoxin composition in venoms from
      different localities. 

PMID- 25064256
TI  - Lipid-water partition coefficients and correlations with uptakes by algae of
      organic compounds.
AB  - In view of the scarcity of the lipid-water partition coefficients (Ktw) for
      organic compounds, the logKtw values for many environmental contaminants were
      measured using ultra-pure triolein as the model lipid. Classes of compounds
      studied include alkyl benzenes, halogenated benzenes, short-chain chlorinated
      hydrocarbons, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and
      organochlorine pesticides. In addition to logKtw determination, the uptakes of
      these compounds from water by a dry algal species were measured to evaluate the
      lipid effect on the algal uptake. The measured logKtw are closely related to
      their respective logKow (octanol-water), with logKow=1.9 to 6.5. A significant
      difference is observed between the present and early measured logKtw for
      compounds with logKow>~5, which is attributed to the presence and absence of a
      triolein microemulsion in water affecting the solute partitioning. The observed
      lipid-normalized algae-water distribution coefficients (logKaw/lipid) are
      virtually identical to the respective logKtw values, which manifests the dominant
      lipid-partition effect of the compounds with algae. 

PMID- 25064257
TI  - Removal of sulfonamide antibiotics by oriented immobilized laccase on Fe3O4
      nanoparticles with natural mediators.
AB  - A novel strategy was applied in the oriented immobilization of laccase from
      Echinodontium taxodii on concanavalin A-activated Fe3O4 nanoparticles (GAMNs-Con
      A) based on laccase surface analysis. These nanoparticles showed higher enzyme
      loading and activity recovery compared with conventional covalent binding. Along
      with the improvement in thermal and operational stabilities, the oriented
      immobilized laccase (GAMNs-Con A-L) exhibited higher substrate affinity than free
      laccase. Free laccase and GAMNs-Con A-L were then applied in the removal of
      sulfonamide antibiotics (SAs). Although both free and immobilized laccase
      resulted in the rapid removal of SAs, GAMNs-Con A-L showed a higher removal rate
      of SAs compared with the free counterpart in the presence of S-type compounds
      present in lignin structure. Syringic acid mediated the fastest removal
      efficiency of SAs among S-type compounds and resulted in an almost complete
      removal of these substances after incubation for 5min. The oxidation products of
      SAs were identified via LC-ESI(+)-MS. The results suggested the transformation of
      SAs and S-type compounds were catalyzed by laccase, resulting in the formation of
      cross-coupled products. 

PMID- 25064258
TI  - Effect of iron oxide reductive dissolution on the transformation and
      immobilization of arsenic in soils: New insights from X-ray photoelectron and X
      ray absorption spectroscopy.
AB  - The geochemical behavior and speciation of arsenic (As) in paddy soils is
      strongly controlled by soil redox conditions and the sequestration by soil iron
      oxyhydroxides. Hence, the effects of iron oxide reductive dissolution on the
      adsorption, transformation and precipitation of As(III) and As(V) in soils were
      investigated using batch experiments and synchrotron based techniques to gain a
      deeper understanding at both macroscopic and microscopic scales. The results of
      batch sorption experiments revealed that the sorption capacity of As(V) on anoxic
      soil was much higher than that on control soil. Synchrotron based X-ray
      fluorescence (MU-XRF) mapping studies indicated that As was heterogeneously
      distributed and was mainly associated with iron in the soil. X-ray absorption
      near edge structure (XANES), micro-X-ray absorption near edge structure (MU
      XANES) and X-ray photoelectron spectroscopy (XPS) analyses revealed that the
      primary speciation of As in the soil is As(V). These results further suggested
      that, when As(V) was introduced into the anoxic soil, the rapid coprecipitation
      of As(V) with ferric/ferrous ion prevented its reduction to As(III), and was the
      main mechanism controlling the immobilization of As. This research could improve
      the current understanding of soil As chemistry in paddy and wetland soils. 

PMID- 25064259
TI  - Oxidative desulfurization of model diesel via dual activation by a protic ionic
      liquid.
AB  - A novel and green carboxylate-anion-based protic ionic liquid (PIL), [Hnmp]HCOO,
      was prepared through a simple and atom economic neutralization reaction between N
      methyl-2-pyrrolidonium (NMP) and formic acids. Both FT-IR spectra and (1)H NMR
      confirmed its simple salt structure. [Hnmp]HCOO exhibited so high catalytic
      activity that the dibenzothiophene (DBT) removal reached 99% at 50 degrees C in
      3h under conditions of VPIL/Vmodel oil=1:10 and H2O2/DBT (O/S, molar ratio)=5.
      The catalytic oxidation reactivity of S-compounds was found to be in the order of
      DBT>4,6-dimethyldibenzothiophene (4,6-DMDBT)>benzothiophene (BT). The
      investigation on mechanism showed that oxidative desulfurization was realized
      through dual activation of PIL. Moreover, [Hnmp]HCOO can be recycled for five
      times with an unnoticeable decrease in desulfurization activity. 

PMID- 25064260
TI  - Promoting effect of alkaline earth metal doping on catalytic activity of HC and
      NOx conversion over Pd-only three-way catalyst.
AB  - The influence of alkaline earth metal (M=Mg, Ca, Sr and Ba) promoter on the
      structural/textural properties of Ce0.67Zr0.33O2 (designated as CZ) and the
      catalytic behavior of its supported Pd-only three-way catalyst (Pd/CZM) have been
      investigated. The results show that the modification with alkaline earth metal
      obviously improves the catalytic activity for hydrocarbon (HC) and nitrogen
      oxides (NOx) conversion, especially the introduction of Ba. Furthermore, the
      operation window of the promoted catalysts has also been widened. The doping of
      alkaline earth metal leads to the formation of more homogeneous Ce-Zr-M ternary
      solid solution with higher surface area and smaller crystallite size, and the
      corresponding Pd/CZM catalysts present improved reducibility of PdO species. The
      modification with Ca, Sr and Ba improves the thermal aging resistance, especially
      Ba. DRIFTS results reveal that the doping of alkaline earth metal enhances the
      oxygen and electron transfer ability and favors the dissociation of NO, which
      promotes the activation and storage capacity of the acidic atoms like NOx, and
      leads to enhanced catalytic activity performance. 

PMID- 25064261
TI  - The synergism of temperature, pH and growth phases on heavy metal biosorption by
      two environmental isolates.
AB  - In real environmental applications, such as heavy metal bioremediation,
      microorganisms are generally not kept at their optimum growth conditions;
      therefore, it is imperative to investigate their heavy metal removal performance
      under diverse environmental conditions. The present study aims to investigate the
      effects of pH, temperature and growth phases on the removal of Cu(2+) and Cr(6+)
      by two environmental isolates identified as Ochrobactrum intermedium LBr and
      Cupriavidus metallidurans CH34. Results showed that cells in logarithmic phase
      presented better biosorption capacity than cells in stationary phase for both
      isolates. The Cr(6+) metal was removed more efficiently by live O. intermedium
      LBr than dead cells; while dead C. metallidurans CH34 biosorbed better than live
      ones. It was also found that the pH and temperature affected the biosorption
      capacity. The optimum temperatures were determined to be 37 degrees C and 27
      degrees C, and the optimum pH values were 6 and 7 for O. intermedium LBr and C.
      metallidurans CH34, respectively. Additionally, both microorganisms
      preferentially adsorbed Cu(2+) in Cu(2+)/Cr(6+) mixtures. The main mechanism of
      adsorption was determined to be through carboxylic, hydroxyl, and amino
      functional groups. 

PMID- 25064262
TI  - Molecular characterization of biochars and their influence on microbiological
      properties of soil.
AB  - The tentative connection between the biochar surface chemical properties and
      their influence on microbially mediated mineralization of C, N, and S with the
      help of enzymes is not well established. This study was designed to investigate
      the effect of different biomass conversion processes (microwave pyrolysis, carbon
      optimized gasification, and fast pyrolysis using electricity) on the composition
      and surface chemistry of biochar materials produced from corn stover (Zea mays
      L.), switchgrass (Panicum virgatum L.), and Ponderosa pine wood residue (Pinus
      ponderosa Lawson and C. Lawson) and determine the effect of biochars on
      mineralization of C, N, and S and associated soil enzymatic activities including
      esterase (fluorescein diacetate hydrolase, FDA), dehydrogenase (DHA), beta
      glucosidase (GLU), protease (PROT), and aryl sulfatase (ARSUL) in two different
      soils collected from footslope (Brookings) and crest (Maddock) positions of a
      landscape. Chemical properties of biochar materials produced from different
      batches of gasification process were fairly consistent. Biochar materials were
      found to be highly hydrophobic (low H/C values) with high aromaticity,
      irrespective of biomass feedstock and pyrolytic process. The short term
      incubation study showed that biochar had negative effects on microbial activity
      (FDA and DHA) and some enzymes including beta-glucosidase and protease. 

PMID- 25064263
TI  - Stochastic goal programming based groundwater remediation management under human
      health-risk uncertainty.
AB  - An optimal design approach for groundwater remediation is developed through
      incorporating numerical simulation, health risk assessment, uncertainty analysis
      and nonlinear optimization within a general framework. Stochastic analysis and
      goal programming are introduced into the framework to handle uncertainties in
      real-world groundwater remediation systems. Carcinogenic risks associated with
      remediation actions are further evaluated at four confidence levels. The
      differences between ideal and predicted constraints are minimized by goal
      programming. The approach is then applied to a contaminated site in western
      Canada for creating a set of optimal remediation strategies. Results from the
      case study indicate that factors including environmental standards, health risks
      and technical requirements mutually affected and restricted themselves.
      Stochastic uncertainty existed in the entire process of remediation optimization,
      which should to be taken into consideration in groundwater remediation design. 

PMID- 25064264
TI  - Performance evaluation of nursing students following competency-based education.
AB  - BACKGROUND: Competency-based education is known to improve the match between
      educational performance and employment opportunities. OBJECTIVES: This study
      examined the effects of competency-based education on the learning outcomes of
      undergraduate nursing students. DESIGN: The study used a quasi-experimental
      design. PARTICIPANTS: A convenience sample of 312 second-year undergraduate
      nursing students from northern and southern Taiwan participated in the study.
      METHODS: The experimental group (n=163) received competency-based education and
      the control group received traditional instruction (n=149) in a medical-surgical
      nursing course. Outcome measures included students' scores on the Objective
      Structured Clinical Examination, Self-Evaluated Core Competencies Scale,
      Metacognitive Inventory for Nursing Students questionnaire, and academic
      performance. RESULTS: Students who received competency-based education had
      significantly higher academic performance in the medical-surgical nursing course
      and practicum than did the control group. Required core competencies and
      metacognitive abilities improved significantly in the competency-based education
      group as compared to the control group after adjusting for covariates.
      CONCLUSIONS: Competency-based education is worth implementing and may close the
      gap between education and the ever-changing work environment.

PMID- 25064265
TI  - A contemporary examination of workplace learning culture: an ethnomethodology
      study.
AB  - BACKGROUND: Creating and maintaining a sustainable workforce is currently an
      international concern. Extensive literature suggest that students and staff need
      to be 'engaged', that is they need to interact with the health team if they are
      to maximise learning opportunities. Despite many studies since the 1970s into
      what creates a 'good' learning environment, ongoing issues continue to challenge
      healthcare organisations and educators. A 'good' learning environment has been an
      intangible element for many professions as learning is hindered by the complexity
      of practice and by limitations on practitioners' time available to assist and
      guide novices. OBJECTIVES: This study sought to explore the nature of the
      learning interactions and experiences in clinical nursing practice that enhance a
      'good' workplace learning culture for both nursing students and qualified nurses.
      DESIGN: An ethnomethodology study. SETTING: A range of clinical settings in
      Victoria and Queensland, Australia. PARTICIPANTS: Students and registered nurses
      (n=95). METHODS: Fieldwork observations were carried out on student nurses and
      registered nurses, followed by an individual interview with each participant. An
      iterative approach to analysis was undertaken; field notes of observations were
      reviewed, interviews transcribed verbatim and entered into NVivo10. Major themes
      were then extracted. RESULTS: Three central themes: learning by doing, navigating
      through communication, and 'entrustability', emerged providing insights into
      common practices potentially enhancing or detracting from learning in the
      workplace. CONCLUSIONS: Students' and registered nurses' learning is constrained
      by a myriad of interactions and embedded workplace practices, which can either
      enhance the individual's opportunities for learning or detract from the richness
      of affordances that healthcare workplace settings have to offer. Until the
      culture/or routine practices of the healthcare workplace are challenged, the
      trust and meaningful communication essential to learning in practice, will be
      achievable only serendipitously.

PMID- 25064266
TI  - HIV-1 translation and its regulation by cellular factors PKR and PACT.
AB  - The synthesis of proteins from viral mRNA is the first step towards viral
      assembly. Viruses are dependent upon the cellular translation machinery to
      synthesize their own proteins. The synthesis of proteins from the human
      immunodeficiency virus (HIV) type 1 and 2 RNAs utilize several alternative
      mechanisms. The regulation of viral protein production requires a constant
      interplay between viral requirements and the cell response to viral infection.
      Among the antiviral cell responses, the interferon-induced RNA activated protein
      kinase, PKR, regulates the cellular and viral translation. During HIV-1
      infection, PKR activation is highly regulated by viral and cellular factors. The
      cellular TAR RNA Binding Protein, TRBP, the Adenosine Deaminase acting on RNA,
      ADAR1, and the PKR Activator, PACT, play important roles. Recent data show that
      PACT changes its function from activator to inhibitor in HIV-1 infected cells.
      Therefore, HIV-1 has evolved to replicate in cells in which TRBP, ADAR1 and PACT
      prevent PKR activation to allow efficient viral protein synthesis. This proper
      translation will initiate the assembly of viral particles. 

PMID- 25064267
TI  - Pneumonitis in Syrian golden hamsters (Mesocricetus auratus) infected with Rio
      Mamore virus (family Bunyaviridae, genus Hantavirus).
AB  - Rio Mamore virus is an etiological agent of hantavirus pulmonary syndrome in
      South America. The purpose of this study was to determine whether Rio Mamore
      virus strain HTN-007 in Syrian golden hamsters is pathogenic. None of 37 adult
      hamsters infected by intramuscular injection of HTN-007, including 10 animals
      killed on Day 42 or 43 post-inoculation, exhibited any symptom of disease.
      Histological abnormalities included severe or moderately severe pneumonitis in 6
      (46.2%) of the 13 animals killed on Day 7 or 10 post-inoculation. The primary
      target of infection in lung was the endothelium of the microvasculature.
      Collectively, these results indicate that Rio Mamore virus strain HTN-007 in
      adult Syrian golden hamsters can cause a nonlethal disease that is pathologically
      similar to hantavirus pulmonary syndrome. 

PMID- 25064268
TI  - A longitudinal study of the prevalence and super-shedding of Escherichia coli
      O157 in dairy heifers.
AB  - The fecal shedding and super-shedding of the human pathogen Escherichia coli O157
      by cattle has been the focus of many previous studies with varied results
      observed. The heterogeneity of shedding is becoming more accepted, both in the
      numbers of animals shedding and the levels at which animals shed. To clarify
      patterns in shedding and super-shedding we undertook a longitudinal study to
      investigate shedding within a cohort of replacement dairy heifers. The cohort of
      52 heifers was sampled 18 times at approximately weekly intervals with no
      significant changes in management during the sampling period. An overall
      prevalence of 44.3% (412/930 samples) was detected with prevalence ranging from
      9.6 to 94.3% at individual sampling points. Each of the 52 heifers yielded at
      least one sample which was detected positive for E. coli O157. Super-shedding was
      detected at a sample level of 3.6% (32/893) and ranged between 0 and 9.6% at each
      sampling point. Of the 52 heifers, 24 (46.2%) were detected to be super-shedding
      at some point during the study, 19 of which were detected as super-shedding at
      only one point. From our findings we conclude that super-shedding is not
      associated with a small subset of animals that shed at high levels continually as
      had been proposed by earlier studies. We propose that the term 'super-shedding
      event' as opposed to 'super-shedding animal' better describes the nature of
      shedding. 

PMID- 25064269
TI  - Nonparametric pore size distribution using d-PFG: comparison to s-PFG and
      migration to MRI.
AB  - Here we present the successful translation of a pore size distribution (PSD)
      estimation method from NMR to MRI. This approach is validated using a well
      characterized MRI phantom consisting of stacked glass capillary arrays (GCA)
      having different diameters. By employing a double pulsed-field gradient (d-PFG)
      MRI sequence, this method overcomes several important theoretical and
      experimental limitations of previous single-PFG (s-PFG) based MRI methods by
      allowing the relative diffusion gradients' direction to vary. This feature adds
      an essential second dimension in the parameters space, which can potentially
      improve the reliability and stability of the PSD estimation. To infer PSDs from
      the MRI data in each voxel an inverse linear problem is solved in conjunction
      with the multiple correlation function (MCF) framework, which can account for
      arbitrary experimental parameters (e.g., long diffusion pulses). This scheme
      makes no a priori assumptions about the functional form of the underlying PSD.
      Creative use of region of interest (ROI) analysis allows us to create different
      underlying PSDs using the same GCA MRI phantom. We show that an s-PFG experiment
      on the GCA phantom fails to accurately reconstruct the size distribution, thus
      demonstrating the superiority of the d-PFG experiment. In addition, signal
      simulations corrupted by different noise levels were used to generate continuous
      and complex PSDs, which were then successfully reconstructed. Finally, owing to
      the reduced q- or b- values required to measure microscopic PSDs via d-PFG MRI,
      this method will be better suited to biomedical and clinical applications, in
      which gradient strength of scanners is limited. 

PMID- 25064270
TI  - Electron spin echo and spin relaxation of low-symmetry Mn(2+)-complexes in
      ammonium oxalate monohydrate single crystal.
AB  - Pulse EPR experiments were performed on low concentration Mn(2+) ions in ammonium
      oxalate monohydrate single crystals at X-band, in the temperature range 4.2-60K
      at crystal orientation close to the D-tensor z-axis. Hyperfine lines of the
      resolved spin transitions were selectively excited by short nanosecond pulses.
      Electron spin echo signal was not observed for the low spin transition (+5/2<
      >+3/2) suggesting a magnetic field threshold for the echo excitation. Echo
      appears for higher spin transitions with amplitude, which grows with magnetic
      field. Opposite behavior displays amplitude of echo decay modulations, which is
      maximal at low field and negligible for high field spin transitions. Electron
      spin-lattice relaxation was measured by the pulse saturation method. After the
      critical analysis of possible relaxation processes it was concluded that the
      relaxation is governed by Raman T(7)-process. The relaxation is the same for all
      spin transitions except the lowest temperatures (below 20K) where the high field
      transitions (-3/2<->-1/2) and (-5/2<->-3/2) have a slower relaxation rate.
      Electron spin echo dephasing is produced by electron spectral diffusion mainly,
      with a small contribution from instantaneous diffusion for all spin transitions.
      For the highest field transition (-5/2<->-3/2) an additional contribution from
      nuclear spectral diffusion appears with resonance type enhancement at low
      temperatures. 

PMID- 25064271
TI  - Host range of the potential biopesticide Pea Albumin 1b (PA1b) is limited to
      insects.
AB  - The Pea Albumin 1 subunit b (PA1b) peptide is an entomotoxin extracted from
      legume seeds with lethal activity towards several insect pests. Its toxic
      activity occurs after the perception of PA1b by a plasmalemmic proton pump (V
      ATPase) in the insects. Assays revealed that PA1b showed no activity towards
      mammalian cells displaying high V-ATPase activity. Similarly, PA1b displayed no
      binding activity and no biological activity towards other non-insect organisms.
      We demonstrate here that binding to labelled PA1b was found in all the insect
      families tested, regardless of the sensitivity or insensitivity of the individual
      species. The coleopteran Bruchidae, which are mainly legume seed pests, were
      found to be fully resistant. A number of insect species were seen to be
      insensitive to the toxin although they exhibited binding activity for the
      labelled PA1b. The fruit fly, Drosophila melanogaster (Diptera), was generally
      insensitive when maintained on an agar diet, but the fly appeared to be sensitive
      to PA1b in bioassays using a different diet. In conclusion, the PA1b toxin
      provides legumes with a major source of resistance to insects, and insects
      feeding on legume seeds need to overcome this plant resistance by disrupting the
      PA1b - V-ATPase interaction. 

PMID- 25064272
TI  - Application of passive (SPATT) and active sampling methods in the profiling and
      monitoring of marine biotoxins.
AB  - Solid phase adsorbent and toxin tracking (SPATT) enables temporally and spatially
      integrated monitoring of biotoxins in aquatic environments. Monitoring using two
      adsorbent resins was performed over a four-month period at Lough Hyne Marine
      Reserve, Ireland. A range of Diarhettic Shellfish Poisoning (DSP) toxins were
      detected from SPATT extracts throughout the study period. The majority of
      biotoxins were detected in the top 20-30 m of the water column and a spike in
      toxin accumulation was measured during August 2010. Phytoplankton analysis
      confirmed the presence of toxin-producing species Dinophysis acuta and Dinophysis
      acuminata during the bloom. SPATT has the potential to provide useful information
      on phycotoxin distribution in the water column; enabling evidence-based decisions
      regarding appropriate depths for obtaining phytoplankton and shellfish samples in
      marine biotoxin monitoring programmes. Active sampling was performed continuously
      over 7-days and high quantities of toxins were successfully accumulated in the HP
      20 resin, okadaic acid (~13 mg), dinophysis toxin-2 (~29 mg), pectenotoxin-2 (~20
      mg) and pectenotoxin-2-seco acid (~6 mg) proving this an effective method for
      accumulating DSP toxins from the marine environment. The method has potential
      application as a tool for assessing toxin profiles at proposed shellfish
      harvesting sites. 

PMID- 25064273
TI  - The localization of exogenous microcystin LR taken up by a non-microcystin
      producing cyanobacterium.
AB  - The effect of exogenous microcystin on non-microcystin producing cyanobacteria
      has not yet been extensively studied. Existing evidence for internalization of
      microcystin by cyanobacteria is based only on the presence of internalized
      radioisotopic label. Where a function or physiological role for microcystin has
      been proposed based on the molecule acting as a signalling molecule, the
      hypothetical function has not been demonstrated at the site of action in
      receiving cells. We therefore exposed Synechocystis PCC6803 to microcystin LR and
      showed that the microcystin-LR was both taken up by Synechocystis PCC6803 and
      localised in the thylakoid membranes, where it caused a decrease in photosystem
      II activity as has been shown for endogenous microcystin, without any negative
      effects on the cell's survival. 

PMID- 25064274
TI  - Discrimination of tiger using a novel high resolution melting (HRM) and multiplex
      SNP-specific HRM (MSS-HRM) technique.

PMID- 25064276
TI  - Safety of percutaneous endoscopic gastrostomy after trauma laparotomy.
AB  - BACKGROUND: Trauma patients frequently require long-term enteral access because
      of injuries to the head, neck, or gastrointestinal tract. Noninvasive methods for
      gastrostomy placement include percutaneous endoscopic gastrostomy (PEG) and
      percutaneous radiographic gastrostomy (PRG). In patients with recent trauma
      laparotomy, PEG placement is felt to be relatively contraindicated because of the
      concerns about altered anatomy. We hypothesize that there is no increased rate of
      complications related to PEG placement in patients with trauma laparotomy
      compared with those without laparotomy provided that basic safety principles are
      followed. MATERIALS AND METHODS: This retrospective study evaluates all
      percutaneous gastrostomies (both PEG and PRG) placed in trauma patients admitted
      at a level I trauma center between January 1, 2007 and March 30, 2010. The
      electronic medical records of the 354 patients were reviewed through 30 days
      after procedure, and patients were further subdivided by the history of
      laparotomy. Statistical analysis was performed using Fisher exact test or two
      tailed t-test, as appropriate. RESULTS: In patients with no prior trauma
      laparotomy, successful PEG placement occurred in 92.2% of patients, the remainder
      underwent PRG placement. Of patients with prior trauma laparotomy, 82.4% had
      successful PEG placement. Two percent of attempted PEG placements failed in
      patients with no previous trauma laparotomy, whereas 11.8% failed in patients
      with recent trauma laparotomy. The overall complication rate was 2.0%, with no
      recorded complications in patients with trauma laparotomy before PEG placement.
      CONCLUSIONS: These data suggest that surgeons should not consider recent trauma
      laparotomy a contraindication to PEG placement.

PMID- 25064275
TI  - Metabolite and transcript profiling of berry skin during fruit development
      elucidates differential regulation between Cabernet Sauvignon and Shiraz
      cultivars at branching points in the polyphenol pathway.
AB  - BACKGROUND: Grapevine berries undergo complex biochemical changes during fruit
      maturation, many of which are dependent upon the variety and its environment. In
      order to elucidate the varietal dependent developmental regulation of primary and
      specialized metabolism, berry skins of Cabernet Sauvignon and Shiraz were
      subjected to gas chromatography-mass spectrometry (GC-MS) and liquid
      chromatography-mass spectrometry (LC-MS) based metabolite profiling from pre
      veraison to harvest. The generated dataset was augmented with transcript
      profiling using RNAseq. RESULTS: The analysis of the metabolite data revealed
      similar developmental patterns of change in primary metabolites between the two
      cultivars. Nevertheless, towards maturity the extent of change in the major
      organic acid and sugars (i.e. sucrose, trehalose, malate) and precursors of
      aromatic and phenolic compounds such as quinate and shikimate was greater in
      Shiraz compared to Cabernet Sauvignon. In contrast, distinct directional
      projections on the PCA plot of the two cultivars samples towards maturation when
      using the specialized metabolite profiles were apparent, suggesting a cultivar
      dependent regulation of the specialized metabolism. Generally, Shiraz displayed
      greater upregulation of the entire polyphenol pathway and specifically higher
      accumulation of piceid and coumaroyl anthocyanin forms than Cabernet Sauvignon
      from veraison onwards. Transcript profiling revealed coordinated increased
      transcript abundance for genes encoding enzymes of committing steps in the
      phenylpropanoid pathway. The anthocyanin metabolite profile showed F3'5'H
      mediated delphinidin-type anthocyanin enrichment in both varieties towards
      maturation, consistent with the transcript data, indicating that the F3'5'H
      governed branching step dominates the anthocyanin profile at late berry
      development. Correlation analysis confirmed the tightly coordinated metabolic
      changes during development, and suggested a source-sink relation between the
      central and specialized metabolism, stronger in Shiraz than Cabernet Sauvignon.
      RNAseq analysis also revealed that the two cultivars exhibited distinct pattern
      of changes in genes related to abscisic acid (ABA) biosynthesis enzymes.
      CONCLUSIONS: Compared with CS, Shiraz showed higher number of significant
      correlations between metabolites, which together with the relatively higher
      expression of flavonoid genes supports the evidence of increased accumulation of
      coumaroyl anthocyanins in that cultivar. Enhanced stress related metabolism, e.g.
      trehalose, stilbene and ABA in Shiraz berry-skin are consistent with its
      relatively higher susceptibility to environmental cues.

PMID- 25064277
TI  - An exploration of the influence of thinness expectancies and eating pathology on
      compensatory exercise.
AB  - Compensatory exercise (exercise performed in an effort to control weight/shape or
      in response to caloric intake) and thinness expectancies (beliefs that thinness
      will improve the overall quality of life) are strongly linked to the development,
      maintenance, severity, and outcome of eating disorders. There is little
      literature, however, examining the relationship between compensatory exercise and
      thinness expectancies. The goal of the current study was to examine whether
      thinness expectancies contribute significant variance in the endorsement of
      excessive exercise over and above binge eating, restraint, and shape and weight
      concerns. A total of 677 undergraduate women (mean age=18.73) completed self
      report measures of thinness expectancies and eating disorder symptoms (TREI and
      EDE-Q). There was a significant association between thinness expectancies and
      frequency of compensatory exercise behavior. Restraint and subjective binge
      episodes accounted for significant variance in compensatory exercise. Frequency
      of objective binge episodes did not, nor did endorsement of thinness
      expectancies. These findings suggest a potential profile of individuals engaging
      in compensatory exercise as individuals who actively restrict their diets, feel
      as if they have binged when they violate those restrictions, and feel the need to
      excessively exercise to compensate for the subjective binges. 

PMID- 25064278
TI  - A comparison between the feeding practices of parents and grandparents.
AB  - Grandparents play a valuable role in the socialisation of young children, and as
      many as 36% of British parents use grandparents as their main form of childcare.
      Research has begun to explore how grandparents impact the social and cognitive
      development of children, but very little research has evaluated their
      contribution to child feeding. The present study explores whether there are
      differences between parents and grandparents in terms of their feeding practices,
      and whether grandparents' feeding practices are related to the number of hours
      that they spend caring for grandchildren. Results indicate that grandparents
      reported using significantly more maladaptive feeding practices such as using
      food to regulate emotions and restricting food, but more positive practices such
      as providing a healthy food environment. The more hours that grandparents spent
      caring for children the more their feeding practices resembled those broadly
      reported by parents. Results suggest that grandparents can have a measurable
      impact on child feeding behaviour which in turn is likely to predict the eating
      behaviours of their grandchildren. 

PMID- 25064279
TI  - Examining the role of negative urgency in a predictive model of bulimic symptoms.
AB  - The etiological dual pathway model of bulimia nervosa suggests that dietary
      restraint and negative affect are significant predictors of this disorder.
      Negative urgency, or the tendency to act rashly in response to negative
      emotionality, is also associated with bulimia nervosa; however, no study has
      examined the role of negative urgency within the context of the dual pathway
      model. The purpose of this study was to investigate the relationship between
      bulimic symptomatology and negative urgency in the context of dietary restraint
      and depressive affect. Participants (N=166) were college women recruited from a
      private mid-western university through an online participant registry. A self
      report battery assessed depressive affect, dietary restraint, negative urgency,
      and bulimic symptoms. Participants' height and weight were measured in-person to
      determine body mass index. A significant main effect of negative urgency was
      found after controlling for depressive affect and dietary restraint. The
      interaction between depressive affect and negative urgency to predict bulimic
      symptoms approached significance; however, no statistically significant
      interaction between dietary restraint and negative urgency was observed. These
      results provide support for the inclusion of negative urgency as a significant
      factor in etiological frameworks of bulimia nervosa. 

PMID- 25064280
TI  - Internet and patient empowerment in individuals with symptoms of an eating
      disorder: a cross-sectional investigation of a pro-recovery focused e-community.
AB  - INTRODUCTION: Many individuals with eating disorder problems seek information and
      support online. There are however numerous websites that promote eating
      disordered behaviors. The website and e-community 'Proud2Bme' was developed as a
      healthy alternative for pro-eating disorder websites, providing a safe, positive,
      and pro-recovery focused environment. It offers a wide array of information and
      personal stories, as well as platforms for interaction such as a forum and chat.
      The first aim of this study was to investigate whether, and to what extent,
      empowering processes and outcomes are experienced by participants on Proud2Bme.
      The second aim was to examine correlates of empowering processes and outcomes.
      METHODS: Participants (n=311) were recruited via an online survey on Proud2Bme.
      Correlations were examined and T-tests and ANOVAs were conducted. RESULTS:
      Exchanging information, finding recognition, and sharing experiences were the
      empowering processes most often reported by participants. The most pronounced
      empowering outcome was feeling better informed. To a smaller degree, increased
      help-seeking behavior, increased optimism and control over the future, and
      increased confidence in treatment and the relationship with the therapist were
      reported. Lower levels of general empowerment, younger age, and more interactive
      usage patterns of the website were positively associated with the experience of
      empowering processes and outcomes. DISCUSSION: Offering a platform where
      individuals can share their experiences and find recognition might be one of the
      most important ingredients for successful e-health initiatives aimed at improving
      patient empowerment. Moreover, in the field of eating disorders specifically,
      such initiatives offer a healthy alternative to the harmful and negative effects
      of pro-eating disorder websites.

PMID- 25064281
TI  - Prevalence of body dissatisfaction among United States adults: review and
      recommendations for future research.
AB  - As the evidence supporting the role of body dissatisfaction (BD) in chronic
      disease risk factors and health behaviors increases, documenting the prevalence
      of BD is an essential first step in determining to what degree BD is a public
      health problem. Therefore, the primary purpose of this study is to critically
      evaluate research examining the population prevalence of BD among U.S. adults.
      Seven studies were located and provided estimates of prevalence of BD among U.S.
      adults that were extremely varied (11%-72% for women, and 8%-61% for men). While
      some of the variation may be due to increases in BD over time, the literature is
      also clouded by a lack of randomly selected samples, lack of consistency in
      measurement tools, lack of consistency in operational definitions of BD, and lack
      of standardized cut-off points for BD. Recommendations for improving BD
      prevalence research to enable public health research are provided. 

PMID- 25064282
TI  - Obesity stigmatization as the status quo: structural considerations and
      prevalence among young adults in the U.S.
AB  - OBJECTIVE: Although obesity stigmatization contributes to significant health,
      economic, and quality-of-life challenges for U.S. adults, the prevalence and
      nature of stigmatizing attitudes requires an update and clarification. The
      present study sought to examine the prevalence and major dimensions of negative
      attitudes toward obesity through assessment of young U.S. adults' responses to
      the Attitudes Toward Obese Persons Scale. METHOD: Participants were women (n=578)
      and men (n=233) who completed self-report questionnaires assessing obesity
      stigmatization and eating disorder features. RESULTS: Results indicate that at
      least one stigmatizing attitude was endorsed by 92.5% of respondents, with an
      average endorsement rate of 32.8% across items. Eating disorder features, body
      size, and gender were not related to one's likelihood of endorsing negative
      attitudes toward obesity. Distinct clusters of negative attitudes were identified
      involving beliefs that "obese people suffer" and "obese people are inferior."
      DISCUSSION: Data suggest that large proportions of young U.S. adults harbor
      negative attitudes toward obese persons and these attitudes are pervasive across
      individuals with different characteristics. Although such negative attitudes have
      traditionally been conceptualized as relatively unidimensional, results suggest
      that future research would benefit from deconstructing negative attitudes into
      those related to pitying the obese and those related to perceiving the obese with
      harsh judgment.

PMID- 25064283
TI  - Emotional responses to images of food in adults with an eating disorder: a
      comparative study with healthy and clinical controls.
AB  - Emotive responses to foods in people with eating disorders are incompletely
      understood in relation to whether the extent of emotional response is due to the
      eating disorder or non-specific emotional states. The aims of the present study
      were to investigate negative and positive emotive responses to food images in
      adults with an eating disorder, and to compare responses to a (i) healthy and a
      (ii) clinic (psychiatry) control group. Participants viewed 20 images (16 of
      foods previously found to evoke fear, disgust and happiness and 4 neutral images)
      at half-minute intervals and rated emotive responses on 3 visual analogue scales
      for each image. Participants with an eating disorder (n=26) were found to have
      significantly increased negative emotive (disgust and fear) responses and reduced
      positive (happiness) responses to the images compared to the 20 clinic and 61
      healthy participants. Differences between groups remained significant when
      controlling for baseline levels of fear, disgust and happiness. Thus, the emotive
      responses to foods did not appear due to non-specific increases in anxiety or
      depression but rather was due to the presence of an eating disorder. 

PMID- 25064284
TI  - Motivation for change as a predictor of eating disorder treatment outcomes using
      a brief self-report YBC-EDS in a residential eating disorder population.
AB  - The aim of this study was to investigate the factor structure and psychometric
      properties of a new brief self-report form of the Yale-Brown-Cornell Eating
      Disorder Scale (YBC-EDS-BSR) in a transdiagnostic eating disorder population, and
      to determine the predictive ability of motivation for change and ego syntonic
      subscales on treatment outcome. Self-report measures of the YBC-EDS-BSR, eating
      pathology, depression, anxiety and obsessive compulsive symptoms were collected
      from 164 individuals entering residential treatment. Of these, 107 individuals
      completed identical measures at discharge. The admission items on the YBC-EDS-BSR
      were examined for factor structure, and subscales were examined for internal,
      convergent and discriminant validity. Multiple regression analysis was used to
      investigate predictive value of the motivation and ego syntonic subscales on two
      measures of treatment outcome. Results indicate that the YBC-EDS-BSR demonstrated
      a robust factor structure and good psychometric properties in this population.
      The predicted ego-syntonic subscale did not emerge as an independent factor. The
      motivation for change subscale significantly predicted treatment outcome on the
      EDE-Q and the EDI-3 Global Maladjustment Scale. The ego-syntonic items and other
      psychopathology measures had no predictive value on treatment outcome. Results
      suggest that motivation for change is a significant predictor of treatment
      outcome over and above baseline psychopathology. 

PMID- 25064285
TI  - Dietary intake modification in response to a participation in a resistance
      training program for sedentary older adults with prediabetes: findings from the
      Resist Diabetes study.
AB  - Engagement in one type of health behavior change may exert a "spillover" effect
      resulting in other behavior changes. Few studies have examined dietary intake
      following prolonged training, and none have evaluated spontaneous dietary changes
      beyond alterations in energy or macronutrient intake following initiation of
      strength/resistance training (RT). The purpose of this observational
      investigation was to determine if spontaneous dietary intake modifications occur
      in response to initiation of an RT program, among older adults. Previously
      sedentary adults with prediabetes (n=134, age=59+/-1 years) were enrolled in a
      supervised 12-week RT program. Participants were not given dietary advice or
      encouraged to change eating behaviors. Three non-consecutive 24-hour dietary
      recalls were collected at baseline and after 12 weeks of RT. Reductions in intake
      of energy (1914+/-40 kcal vs. 1834+/-427 kcal, p=0.010), carbohydrate (211.6+/
      4.9 g vs. 201.7+/-5.2 g, p=0.015), total sugar (87.4+/-2.7 g vs. 81.5+/-3.1 g,
      p=0.030), glycemic load (113.4+/-3.0 vs. 108.1+/-3.2, p=0.031), fruits and
      vegetables (4.6+/-0.2 servings vs. 4.1+/-0.2 servings, p=0.018), and sweets and
      desserts (1.1+/-0.07 servings vs. 0.89+/-0.07 servings, p=0.023) were detected
      over time. No changes in other dietary intake variables were observed. Mode of
      exercise and disease state may be important factors in determining whether
      dietary modifications occur with exercise initiation, among previously sedentary
      adults. Successful initiation of RT may represent an opportunity for health care
      professionals to promote beneficial changes in dietary habits, among older adults
      with prediabetes.

PMID- 25064286
TI  - Combination and adaptation of two tools to assess parental feeding practices in
      pre-school children.
AB  - OBJECTIVE: To test a combined version of the Child Feeding Questionnaire and the
      expanded concept of parental control ("covert" and "overt") among Portuguese
      preschool children. METHODS: The final questionnaire comprised 38 items and 9
      subscales. The translated questionnaire was self-administered to 854 mothers of 4
      year-old children from the Generation XXI birth cohort. Maternal and children's
      weight and height and socio-demographic characteristics were measured. The global
      goodness of fit was evaluated by confirmatory factor analysis. Cronbach's alpha
      was used to measure the reliability of subscales. Construct validity was tested
      for different dimensions. RESULTS: A 9-factor model was obtained, after excluding
      five "restriction" items and 1 "overt control" item, with a global goodness of
      fit (CFI=0.961, TLI=0.973, RMSEA=0.057). Cronbach's alpha ranged from 0.684 to
      0.889. Children's body mass index (BMI) was significantly and positively related
      with "perceived parental weight", "perceived child's weight" and "concern about
      child's weight", and inversely related with "pressure to eat", supporting the
      theoretical hypothesis. Maternal BMI was positively related with "perceived
      parental weight". CONCLUSIONS: Our study confirmed the usefulness of this
      questionnaire for Portuguese preschool children, and supports the need of
      reformulating the restriction dimension and keeping separately the overt and
      covert control dimensions.

PMID- 25064287
TI  - Understanding the roles of self-esteem, self-compassion, and fear of self
      compassion in eating disorder pathology: an examination of female students and
      eating disorder patients.
AB  - The present study examined the relative contributions of self-compassion, fear of
      self-compassion, and self-esteem in eating disorder pathology. One-hundred and
      fifty-five female undergraduate students and 97 females entering eating disorder
      treatment completed the Self-Compassion Scale, Fears of Compassion Scale,
      Rosenberg Self-Esteem Inventory, and Eating Disorder Examination Questionnaire. T
      tests revealed that the patient group had lower mean self-compassion and higher
      mean fear of self-compassion than the student group. When controlling for self
      esteem, high fear of self-compassion emerged as the strongest predictor of eating
      disorder pathology in the patient group, whereas low self-compassion was the
      strongest predictor in the student group. These preliminary results suggest that
      targeting fear of self-compassion may be important when intervening with
      individuals suffering from an eating disorder, whereas building self-compassion
      may be a valuable approach for eating disorder prevention. 

PMID- 25064288
TI  - Can the impact of body dissatisfaction on disordered eating be weakened by one's
      decentering abilities?
AB  - Decentering has been defined as the ability to deal with thoughts and emotions as
      subjective and ephemeral inner events. Since it implies a non-judging and present
      focused attitude towards thoughts and emotions, decentering has been considered
      as an important protective process against psychopathology, as it has been
      empirically shown to decrease depressive relapse rates. Nevertheless, its role in
      eating disordered attitudes and behaviours has not been fully uncovered.
      Therefore, the aim of the present study is to explore the moderator effect of
      decentering on the relationship between eating psychopathology and one of its
      main risk factors, body image dissatisfaction. The sample comprised 279 female
      students, aged between 14 and 21 years-old. Results revealed that decentering
      abilities were negatively linked to body image dissatisfaction and to the global
      score of eating psychopathology. Through a path analysis, the buffer effect of
      decentering was confirmed. The findings suggest that the ability to take a non
      judgmental and accepting stance towards internal experiences diminishes the
      impact of one's body dissatisfaction on disordered eating attitudes and
      behaviours. This study seems especially pertinent since it uncovers a mechanism
      to lessen the pervasive impact of body image dissatisfaction, which is highly
      prevalent in women from Western societies.

PMID- 25064289
TI  - Mirror, mirror on the wall: how women learn body dissatisfaction.
AB  - Extensive research indicates that exposure to media as well as pressure and
      modeling by sociocultural agents, such as peers and family, are predictive of the
      development of body image dissatisfaction (BID). This influence is mediated by
      social comparison and internalization of the thin-ideal. In the current study we
      assessed comparisons between participants and other women with whom they were in
      close relationships, (e.g. mother, sister and close female friend), and
      hypothesized that these would influence women's BID and drive-to-thinness. 283
      women between the ages of 18-42 (mean=25.04; SD=3.53) sampled through social
      networking completed an online self-report which included the original Figure
      Rating Scale, which yielded self-ideal disparity, as well as a modified version
      comparing self to mother, self to sister closest-in-age, and self to best friend
      and then were asked to directly compare themselves to these women. In addition
      they completed the EDI-2's drive-for-thinness and body dissatisfaction subscales,
      and reported on Body Mass Index (BMI). Results indicate that comparisons to
      mothers, sisters, and best friend, were all associated with self-ideal disparity.
      BMI only slightly mediated this effect. Comparison to sister and to best friend,
      but not to mother, influenced drive-for-thinness and body dissatisfaction.
      Positive correlations were found between direct and indirect comparisons to
      others. Comparison to best friend was the most influential on body ideal. We
      conclude that comparison to others in close proximity greatly influences women's
      body ideal and may have a formative role in the development of women's body
      dissatisfaction. While women cannot choose their mother and sister closest in
      age, they do choose their best friend; and it is interesting that the comparison
      to the best friend is so influential. 

PMID- 25064290
TI  - The impact of maternal overweight and emotion regulation on early eating
      behaviors.
AB  - Empirical data indicate that the risk for childhood obesity and overweight
      increases when one or both parents are overweight or obese. Such an association,
      however, cannot be entirely explained only by biological factors. Based on
      available literature, we hypothesized that maternal emotion regulation might play
      a role in explaining the intergenerational transfer of overweight and obesity. We
      conducted a quasi-experimental, longitudinal study: (step I) during the third
      trimester of pregnancy of 65 Italian women (33 overweight and 32 non-overweight),
      the Difficulties in Emotion Regulation Scale were administered to assess the
      quality of their emotion regulation strategies; and (step II) seven months after
      the delivery, the feeding interactions between the participants and their babies
      were evaluated in a 20-minute video-recording, by using the Italian version of
      the Observational Scale for Mother-Infant Interaction during Feeding. When
      compared to the non-overweight group, the overweight group had more difficulties
      in emotion regulation, was more psychologically distressed, and had poorer
      feeding interactions with their babies. Perhaps more importantly, the extent to
      which the participants were suffering difficulties in emotion regulation during
      pregnancy predicted, significantly, and beyond the effects of pre-pregnancy
      maternal weight, the quality of the mother-child feeding interactions 7months
      after the delivery.

PMID- 25064291
TI  - Electronic dietary recording system improves nutrition knowledge, eating
      attitudes and habitual physical activity: a randomised controlled trial.
AB  - OBJECTIVE: This study's objective was to investigate whether use of an electronic
      dietary recording system improves nutrition knowledge, eating attitudes and
      habitual physical activity levels compared to use of a food diary and no self
      monitoring. METHODS: Sixty adults aged 20-60 with a body mass index >=25 were
      recruited and randomly assigned to one of three groups: a group using an
      electronic system (EG), a group using a food diary (FD) and a control group using
      nothing (CG) to record food intake. All participants took part in three 60-90
      nutrition seminars and completed three questionnaires on general nutrition
      knowledge, habitual physical activity levels and eating attitudes at the
      beginning and end of the 12-week study. The pre- and post-test scores for each
      questionnaire were analysed using a paired sample t-test. RESULTS: Significant
      improvements in the domain of 'dietary recommendations' were found in the EG
      (p=0.009) and FD groups (p=0.046). Great improvements were found in 'sources of
      nutrients', 'choosing everyday foods' and 'diet-disease relationships' in EG and
      FD groups. EG group showed greater improvement in the work index and sport index.
      CONCLUSION: An electronic dietary recording system may improve eating and
      exercise behaviour in a self-monitoring process.

PMID- 25064292
TI  - Non-medical use of prescription stimulants for weight loss, disordered eating,
      and body image.
AB  - OBJECTIVE: There has been minimal research on the non-medical use of prescription
      stimulants (NMUPS), such as Adderall and Ritalin, normally used to treat
      Attention Deficit Hyperactivity Disorder (ADHD) for the purpose of weight loss.
      The current study examined the prevalence and correlates of this use in a young
      adult sample. METHOD: College students (N=707) completed an online survey
      assessing NMUPS, in general and for weight loss, disordered eating behaviors and
      attitudes, body image, and recreational drug use. RESULTS: Overall, 4.4% of
      participants reported NMUPS for the purpose of weight loss with 56.7% reporting
      receiving the medication from friends. Individuals reporting NMUPS for weight
      loss had higher body image concerns and had higher eating disorder
      symptomatology. Vomiting for weight loss as well as laxative, diet pill, or
      diuretic use were robustly associated with NMUPS for weight loss. DISCUSSION:
      Results suggest that NMUPS for weight loss is relatively common and that this
      behavior is related to other harmful behaviors. Eating disorder prevention and
      intervention work should include this behavior when assessing unhealthy weight
      control behaviors.

PMID- 25064293
TI  - Perfectionistic cognitions and eating disturbance: distinct mediational models
      for males and females.
AB  - OBJECTIVE: Perfectionism has long been known to correlate with eating disturbance
      (ED). One mechanism through which this personality tendency may lead to ED is
      through increasing one's daily perfectionistic thoughts. This study examined the
      mediating role of perfectionistic thinking in the personality perfectionism-ED
      relationship among both male and female college students, and included measures
      assessing both typically-male and typically-female ED symptoms. METHOD: A
      majority-White sample of 140 males and 329 females completed online versions of
      the Multidimensional Perfectionism Scale (Hewitt & Flett, 1991), Perfectionism
      Cognitions Inventory (Flett, Hewitt, Blankstein, & Gray, 1998), Drive for
      Muscularity Scale (McCreary, Sasse, Saucier, & Dorsch, 2004), items from the
      Eating Disorder Examination Questionnaire (Fairburn, 2008), and other measures.
      Regression tests examined the hypothesized role of perfectionistic cognitions as
      a mediator, including participant age, BMI, and positive and negative affect as
      covariates. RESULTS: Among women, relationships between both self-oriented
      (Sobel's statistic=-4.63, p<.001) and socially prescribed perfectionism (Sobel's
      statistic=-5.77, p<.001) and dieting behavior were fully mediated by increased
      perfectionistic thinking. Among men, however, the relationship between only self
      oriented perfectionism and bulimic (but not dieting) behavior, was fully mediated
      by increased perfectionistic thinking (Sobel's statistic=-2.53, p=.01).
      CONCLUSIONS: Perfectionistic cognitions play an important linking role between
      personality perfectionism and ED, and can illuminate important differences by
      gender in eating disturbance. Such findings can improve validity of ED assessment
      in both genders, and provide a clear pathway to interventions to decrease ED in
      both genders.

PMID- 25064295
TI  - Relationship between depressive mood and eating disorders in a non-clinical young
      female sample: a one-year longitudinal analysis of cross-lagged and simultaneous
      effects.
AB  - Although it is generally agreed that eating disorders (EDs) and depressive mood
      (DM) are related, the main ambiguity arises from difficulties in determining
      their cause-effect relationships. The aim of this study was to examine the
      longitudinal reciprocal causation between EDs and DM among female students.
      Several models (cross-lagged effects and simultaneous effects) were tested in
      order to disentangle the prospective relationships between DM (measured by the
      Beck Depression Inventory-Short Form) and EDs (measured by the Eating Attitudes
      Test-26) using structural equation modeling with latent variables on one-year
      longitudinal data. A total of 567 female students were interviewed at the
      beginning of the first university year (T1); 373 of them were re-interviewed 6
      months later (T2), and 359 were re-interviewed after a further 6 months (T3). The
      results support (1) the prospective reciprocal effects model and (2) the
      simultaneous reciprocal effects model. The implications of the findings in terms
      of theoretical improvements and effective treatments are discussed.

PMID- 25064294
TI  - The association of "food addiction" with disordered eating and body mass index.
AB  - INTRODUCTION: The contribution of an addictive process to elevated body mass
      index (BMI) and disordered eating is an area of growing interest. Yet, little is
      known about how "food addiction" may be related to disordered eating and obesity.
      The ability of addictive-like eating to account for eating pathology not captured
      by traditional eating disorders is unknown. No prior research has examined the
      association of "food addiction" with bulimia nervosa (BN). Finally, little is
      understood about the association of "food addiction" with patterns of dieting and
      weight gain. The current study was conducted to address these gaps in the
      literature. MATERIAL AND METHODS: Participants (N=815) were recruited from online
      advertisements nationwide and completed measures related to "food addiction",
      BMI, weight history, and disordered eating. RESULTS: Addictive-like eating was
      associated with elevated current and lifetime highest BMI, weight cycling, and
      eating pathology. The prevalence of "food addiction" was higher in participants
      with BN than in those with binge eating disorder (BED). "Food addiction"
      continued to be related to clinically relevant variables, especially elevated
      BMI, even when participants did not meet criteria for BED or BN. The co
      occurrence of "food addiction" with eating disorders appears to be associated
      with a more severe variant of eating pathology. DISCUSSION: An addictive-type
      response to highly palatable food may be contributing to eating-related problems,
      including obesity and eating disorders. BN relative to BED appears to be more
      strongly associated with "food addiction." Additionally, the concept of "food
      addiction" appears to capture clinically relevant information in participants who
      do not meet criteria for either BN or BED. Further examination of "food
      addiction" may be important in understanding the mechanisms underlying certain
      types of problematic eating behavior.

PMID- 25064296
TI  - Sexual orientation and disordered eating behaviors among self-identified male and
      female college students.
AB  - This study compared the risk of a) clinically diagnosed eating disorders, and b)
      disordered eating behaviors, separately among three groups of United States
      college students, controlling for known covariates. These groups included college
      students self-identifying as: 1) gay/lesbian; 2) bisexual; and, 3) unsure, with
      self-identified heterosexuals as the reference. Data from the American College
      Health Association's National College Health Assessment II (2008-2009) were
      utilized (N=110,412). Adjusted logistic regression analyses, stratified by self
      reported gender, examined the effect of self-identified sexual identity on
      clinical eating disorder diagnosis and disordered eating behaviors. Covariates
      included self-reported binge drinking (past 2 weeks), stress (last 12 months),
      smoking (past 30 days), depression (past 12 months), fraternity/sorority
      membership, college athletics participations, and race. Additional logistic
      regression sub-analyses examined sexual minorities only, with gay/lesbian as the
      referent. Gay, unsure, or bisexual men were at significantly increased odds to
      report both clinical eating disorders and disordered eating behaviors when
      compared to heterosexual men in both the unadjusted and adjusted models (p<.002).
      All sexual minority men and women were significantly more likely to report
      dieting to lose weight compared to heterosexual men and women (p<.002). Targeted
      disordered eating and eating disorder prevention efforts are needed for those who
      are sexual minorities, particularly for sexual minority men.

PMID- 25064297
TI  - Attenuated interoceptive sensitivity in overweight and obese individuals.
AB  - OBJECTIVE: Perceiving internal signals of hunger and satiety is related to the
      regulation of food intake. Recent data suggest that interoception (perception of
      bodily signals) and interoceptive sensitivity (sensitivity for internal signals)
      might be a crucial variable for the regulation of behavior associated with
      feelings of satiety. It is yet unclear whether interoceptive sensitivity is
      altered in overweight and obese participants. DESIGN AND METHODS: We therefore
      examined interoceptive sensitivity among 75 overweight and obese women and men
      using a heartbeat detection task and compared them to normal weight controls. We
      hypothesized that overweight and obesity would be related to attenuated
      interoceptive sensitivity. RESULTS: Interoceptive sensitivity was higher in
      normal weight participants as compared to overweight and obese participants.
      Additionally, we found a negative correlation coefficient between the BMI and
      interoceptive sensitivity in the overweight and obese group only. CONCLUSIONS: In
      accordance with our hypotheses, we found evidence for reduced interoceptive
      sensitivity in overweight and obese individuals. Interoceptive sensitivity
      presumably interacts with the regulation of food intake in everyday life in part
      by facilitating the detection of bodily changes accompanying satiety. Overweight
      and obese individuals might experience greater difficulties in accurately
      detecting such signals due to reduced interoceptive sensitivity.

PMID- 25064298
TI  - Interpersonal problems across restrictive and binge-purge samples: data from a
      community-based eating disorders clinic.
AB  - Contemporary models of eating disorders suggest that interpersonal problems
      contribute to the maintenance of eating disorders. This study examined whether
      baseline interpersonal problems differed across eating disorder diagnoses and
      across eating disorder subtypes ("restrictors" vs. "binge-purge" patients) in a
      large clinical sample. Patients with a primary eating disorder diagnosis (N=406)
      completed measures of interpersonal problems, eating disorder symptoms, and mood
      prior to treatment at a specialist eating disorder clinic. Across the sample,
      more severe eating disorder psychopathology was associated with significantly
      greater difficulty socializing. Anorexia Nervosa (AN)/restrictor patients
      reported significantly greater difficulty socializing than Bulimia Nervosa
      (BN)/binge-purge patients. AN patients reported significantly greater difficulty
      on a measure of competitiveness/assertiveness compared to BN and Eating Disorder
      Not Otherwise Specified patients. All findings were significant after controlling
      for comorbid depression and anxiety symptoms. Interpersonal problems appear to be
      unique risk factors for eating disorders. Specific interpersonal mechanisms
      include difficulties socializing and being assertive, which were most pronounced
      in AN patients. These findings provide potential avenues for enhancing
      interventions, such as adjunctive assertiveness training for AN. 

PMID- 25064299
TI  - Body weight dissatisfaction: a comparison of women with and without eating
      disorders.
AB  - OBJECTIVE: Body dissatisfaction is present in a majority of women without eating
      disorders (EDs), and almost all women with EDs. We compared body dissatisfaction
      in women with and without EDs to determine at which BMI women are content with
      their weight, and to determine if body dissatisfaction is affected by the
      presence of purging behaviours. METHODS: We assessed women, age 18 to 55 with an
      ED (N=431) and without an ED (N=719) using the discrepancy between their current
      and desired BMI. This measure of body weight dissatisfaction (BWD) has been
      validated as being representative of overall body dissatisfaction. We also
      measured perceptions of (i) Body Appearance and (ii) Body Image to confirm our
      results. RESULTS: Women with and without EDs wished to lose weight until very low
      weights were achieved (BMI 15-16 kg/m(2) and BMI 18-19 kg/m(2) respectively). BWD
      is higher in women with EDs (median 1.77, IQR 0-4.61) than women without EDs
      (median 0.85, IQR 0-1.80, p<0.001). Purging behaviours in women with EDs were
      associated with lower BMIs to achieve body satisfaction (BMI 15-16 kg/m(2)) than
      women who did not purge (16-17 kg/m(2)). CONCLUSIONS: Body weight dissatisfaction
      is highly prevalent amongst women with and without EDs. Understanding body weight
      dissatisfaction in women with EDs and its association with purging may assist in
      the prevention, detection and treatment of these disorders. Women with EDs should
      be informed that body weight dissatisfaction will not resolve with the cessation
      of their disorder, as it is prevalent within the general population.

PMID- 25064300
TI  - Resilience Scale-25 Spanish version: validation and assessment in eating
      disorders.
AB  - OBJECTIVES: To validate into Spanish the Wagnild and Young Resilience Scale - 25
      (RS-25), assess and compare the scores on the scale among women from the general
      population, eating disorder (ED) patients and recovered ED patients. METHOD: This
      is a cross-sectional study. ED participants were invited to participate by their
      respective therapists. The sample from the general population was gathered via an
      open online survey. Participants (N general population=279; N ED patients=124;
      and N recovered ED patients=45) completed the RS-25, the World Health
      Organization Quality of Life Scale-BREF and the Hospital Anxiety and Depression
      Scale. Mean age of participants ranged from 28.87 to 30.42years old. Statistical
      analysis included a multi-group confirmatory factor analysis and ANOVA. RESULTS:
      The two-factor model of the RS-25 produced excellent fit indexes. Measurement
      invariance across samples was generally supported. The ANOVA found statistically
      significant differences in the RS-25 mean scores between the ED patients
      (Mean=103.13, SD=31.32) and the recovered ED participants (Mean=138.42, SD=22.26)
      and between the ED patients and the general population participants (Mean=136.63,
      SD=19.56). DISCUSSION: The Spanish version of the RS-25 is a psychometrically
      sound measurement tool in samples of ED patients. Resilience is lower in people
      diagnosed with ED than in recovered individuals and the general population.

PMID- 25064301
TI  - A systematic review of family caregiving in eating disorders.
AB  - The objective of the study was to review systematically the available new
      evidence on family caregiving in eating disorders (ED), updating the study of
      Zabala, Macdonald, and Treasure (2009). Electronic databases were searched from
      October 2008 until May 2013. Selected studies included carers of people with ED
      and employed one or more measures of caregiving experience, accommodation and
      enabling behaviours, expressed emotion, and/or psychological distress. Twenty
      nine studies were identified. Most of the studies examined these features in
      mothers of patients with anorexia. Only a few studies included a control group.
      The majority of studies found high levels of negative aspects of caregiving,
      accommodation and enabling behaviours, expressed emotion and psychological
      distress in carers of people with ED, although positive aspects and emotions were
      also reported. These features varied depending on some sociodemographic and
      clinical characteristics of carers and patients; moreover, interesting
      preliminary cultural and gender differences emerged. Progress has been made in
      research on family caregiving in ED and there is evidence that these factors can
      be associated with the outcome of ED. Theoretical, research and clinical
      implications of the findings are discussed. 

PMID- 25064303
TI  - Examining the role of distress tolerance and negative urgency in binge eating
      behavior among women.
AB  - The current study examined whether distress tolerance and negative urgency
      moderate the link between depressive symptoms and binge eating frequency, and
      between disordered eating attitudes and binge eating frequency. Young adult women
      (N=186) completed questionnaires assessing depressive symptoms, cognitive
      restraint, eating, shape and weight concerns, distress tolerance, impulsivity
      (including negative urgency), and binge eating. After controlling for body mass
      index, race/ethnicity, and other domains of impulsivity, negative urgency was
      significantly associated with binge eating above and beyond the influence of
      disordered eating attitudes and depressive symptoms. Distress tolerance, in
      contrast, was not associated with binge eating. In addition, neither negative
      urgency nor distress tolerance moderated the associations between disordered
      eating attitudes and binge eating frequency, or between depressive symptoms and
      binge eating. Results support the additive role of difficulties responding
      adaptively to distress in binge eating frequency, above and beyond the influence
      of emotional distress. Findings highlight the potential value of focusing on
      negative urgency in targeted treatments for binge eating among women.
      Importantly, results from the current study differ from those of previous
      research; these discrepancies could be the result of variations in sample
      characteristics and approaches to the assessment of binge eating behavior.
      Additional research, including longitudinal studies and research using "real
      time" assessment strategies, such as ecological momentary assessment, is
      necessary to elucidate further the role of various emotion regulation strategies
      in maintaining binge eating behavior in adult women. 

PMID- 25064302
TI  - Food cravings, food intake, and weight status in a community-based sample.
AB  - The aims of this study were to 1) determine the relationships between BMI and the
      frequency of food cravings for different categories of foods, 2) examine the
      associations between cravings for different types of foods and self-reported,
      habitual intake of these foods, and 3) assess how these relationships differ by
      BMI. Six hundred and forty-six participants (55.7% female; 66.4% White; mean age
      29.5+/-9.1 years; mean BMI 27.3+/-5.5 kg/m(2)) completed a comprehensive
      assessment battery including the Food Craving Inventory (FCI) and a semi
      quantitative food frequency questionnaire (FFQ). There was a significant positive
      relationship between BMI and food cravings. There were significant positive
      associations of cravings for sweets, high fats, carbohydrates/starches, and fast
      food fats on respective intake of these types of foods; however, there were no
      significant interactions between food cravings and BMI on the respective type of
      food intake. This study indicates significant positive relationships between
      specific categories of food cravings and habitual intake of those foods.

PMID- 25064304
TI  - Construction and validation of the healthy eating and weight self-efficacy
      (HEWSE) scale.
AB  - Healthy eating and weight self-efficacy occurs when individuals believe they can
      obtain and maintain a healthy weight and eating pattern. The goal of this study
      was to develop and evaluate the Healthy Eating and Weight Self-Efficacy (HEWSE)
      Scale. Confirmatory factor analysis indicated that the best fitting model is
      comprised of 11 items divided into two factors - healthy eating and healthy
      weight. Statistical analyses provided evidence that the HEWSE scale is reliable
      and valid. In sum, the HEWSE scale is a brief, psychometrically sound measure of
      healthy eating and weight self-efficacy that may be useful both in research
      studies and in clinical work involving eating and weight. 

PMID- 25064305
TI  - The roles of adolescent attentional bias and parental invalidation of sadness in
      significant illness: a comparison between eating disorders and chronic pain.
AB  - Biopsychosocial conceptualizations of eating disorders (EDs) suggest the
      combination of an individual's emotional vulnerability and invalidating
      environment increases the likelihood of developing pervasive emotion
      dysregulation, and subsequent use of ED behaviors to regulate emotion (Haynos &
      Fruzetti, 2011; Safer, Telch, & Chen, 2009). The current study aimed to provide
      initial support for this model in adolescent EDs, through examining the
      interaction between an adolescent's emotional vulnerability, indexed by
      attentional biases for emotions, and an invalidating family environment.
      Specifically, we examined the ability of this interaction to discriminate youth
      with EDs from a comparison group of youth with chronic pain diagnoses, who were
      used to control for the presence of non-specific effects of having any illness.
      Fifty adolescent girls (25 with EDs and 25 with chronic pain) completed an
      emotional dot-probe task assessing attentional biases for emotional faces, and
      parents completed the Emotions as a Child Scale (Magai, 1996; Klimes-Dougan et
      al., 2007) to assess response to teen emotion. Results showed that teen angry
      attentional bias moderated the relationship between parental response to sadness
      and teen ED status: for teens with high attention bias towards angry faces,
      maladaptive parental response to sadness predicted increased odds of ED status
      versus chronic pain status. 

PMID- 25064306
TI  - Validity of the Bite Counter device in a controlled laboratory setting.
AB  - Body-borne sensors may be useful in assessing eating behaviors and have the
      potential to overcome some of the limitations of self-report instruments. The
      Bite Counter is a new commercial device, worn on the wrist that purports to track
      the number of bites taken per day. It contains a tri-axial accelerometer that
      detects an upward, arcing motion from the table to the mouth, known as a wrist
      roll. PURPOSE: To examine the validity of the Bite Counter device for measuring
      bites in individuals while consuming various foods and beverages. METHODS: 15
      adults (23-58 years old) wore the device on the wrist of their dominant hand.
      They were presented with a meal consisting of foods/beverages, each consumed with
      different utensils: meat (knife and fork), side items (fork), soup (spoon), pizza
      (hands), can of soda (hands), and a smoothie (straw). Each food or drink was
      consumed by itself, in consecutive order. A researcher observed them through a
      one-way mirror and counted the number of bites taken. RESULTS: The percentage of
      actual bites taken varied as follows: Meat (127%), side items (82.6%), soup
      (60.2%), pizza (87.3%), soda (81.7%), and smoothie (57.7%). The overall mean was
      81.2% of bites taken. CONCLUSION: The results indicate that the Bite Counter
      holds promise for being able to count the number of hand-to-mouth movements. In
      general, it underestimated hand-to-mouth movements, but some types of hand
      movements caused overestimation of bites. Future studies should be undertaken to
      improve the sensitivity and specificity of the Bite Counter device.

PMID- 25064307
TI  - Problematic intake of high-sugar/low-fat and high glycemic index foods by
      bariatric patients is associated with development of post-surgical new onset
      substance use disorders.
AB  - Bariatric or weight loss surgery (WLS) patients are overrepresented in substance
      abuse treatment, constituting about 3% of admissions; about 2/3 of such patients
      deny problematic substance use prior to WLS. It is important to advance our
      understanding of the emergence of substance use disorders (SUDs) - particularly
      the New Onset variant - after WLS. Burgeoning research with both animal models
      and humans suggests that "food addiction" may play a role in certain forms of
      obesity, with particular risk conferred by foods high in sugar but low in fat.
      Therefore, we hypothesized that WLS patients who reported pre-WLS problems with
      High-Sugar/Low-Fat foods and those high on the glycemic index (GI) would be those
      most likely to evidence New Onset SUDs after surgery. Secondary data analyses
      were conducted using a de-identified database from 154 bariatric surgery patients
      (88% female, Mage=48.7 yrs, SD=10.8, Mtime since surgery=2.7 yrs, SD=2.2 yrs).
      Participants who endorsed pre-surgical problems with High-Sugar/Low-Fat foods and
      High GI foods were at greater risk for New Onset SUD in the post-surgical period.
      These findings remained significant after controlling for other predictors of
      post-surgical SUD. Our findings provide evidence for the possibility of addiction
      transfer among certain bariatric patients.

PMID- 25064308
TI  - Does nutritional status interfere with adolescents' body image perception?
AB  - Adolescents' body image (BI) may not match their nutritional status. This study
      selected representative sample of healthy adolescents aged between 12 and 18 from
      public and private schools. Anthropometric measures were performed in order to
      calculate the body mass index (BMI) percentile. The silhouette scale proposed by
      Childress was used to evaluate BI, making it possible to assess BI satisfaction
      and BI distortion. The sample was composed of 1168 adolescents with a mean age of
      14.7 years; 52.9% were female, 50.9% were fair-skinned, 62.4% had consumed or
      still consume alcohol and 67% attended public school. Male adolescents presented
      more overweight and obesity (28.4%) (p<0.05) than the female (17.1%). It was
      observed that 69.4% were dissatisfied with BI, 91.1% of the obese and 69.8% of
      those with overweight wished to lose body weight and 82.5% of those underweight
      wished to gain body weight. BI distortion was identified, since 35% of the
      adolescents who were underweight did not regard themselves thin, 39.1% of the
      overweight individuals and 62.1% of the obese did not see themselves in their
      adequate classifications. Adolescents with overweight/obesity were those who
      presented higher dissatisfaction with BI, mainly the females. Male individuals
      presented a greater wish of gaining weight. BI distortion was present in
      adolescents of all classes of BMI percentile.

PMID- 25064309
TI  - Gateway to Care campaign: a public health initiative to reduce the burden of
      hepatitis B in Haimen City, China.
AB  - BACKGROUND: An estimated one million people worldwide die each year from
      complications of chronic hepatitis B infection (CHB), including liver cancer. A
      disproportionate number of infections and deaths occur in China. The incidence
      and mortality of liver cancer in Haimen City is among the highest in China, and
      in the world. A multi-year citywide campaign was aimed at eliminating hepatitis B
      virus (HBV) infection and significantly reducing the number of liver cancer
      deaths due to CHB in Haimen City, China. METHODS: Strategies included a public
      health information campaign targeting the 1.03 million city residents;
      specialized health education for leaders and providers to increase adoption of
      evidence-based HBV management protocols; establishment of health care
      infrastructure and management systems; and increased prevention and care delivery
      to key subpopulations (especially pregnant women). RESULTS: The project developed
      and deployed broad-reaching public awareness and health education tools and
      modules to 280,000 households and at community-based events. More than 90% of
      targeted healthcare providers and 80% of the community leaders/government
      officials attended educational seminars during the project period (1,441 health
      care providers; 1,883 local government officials). A centralized registration and
      management system for pregnant women was developed and instituted, 100% of
      pregnant women were enrolled (5,407 women over one year), and all infants born to
      HBV-infected mothers received one dose of HBIG and the first dose of HBV vaccine
      by 24 hours of birth. CONCLUSIONS: Lessons from the implementation phase of the
      project include the importance of: gaining early and ongoing support from the
      local government and health bureau for success in reaching the targeted
      populations; and having project management by a local, experienced, and trusted
      health expert to navigate implementation and relationships, and help develop
      culturally and linguistically appropriate materials.

PMID- 25064310
TI  - Concept mapping and network analysis: an analytic approach to measure ties among
      constructs.
AB  - Group concept mapping is a mixed-methods approach that helps a group visually
      represent its ideas on a topic of interest through a series of related maps. The
      maps and additional graphics are useful for planning, evaluation and theory
      development. Group concept maps are typically described, interpreted and utilized
      through points, clusters and distances, and the implications of these features in
      understanding how constructs relate to one another. This paper focuses on the
      application of network analysis to group concept mapping to quantify the strength
      and directionality of relationships among clusters. The authors outline the steps
      of this analysis, and illustrate its practical use through an organizational
      strategic planning example. Additional benefits of this analysis to evaluation
      projects are also discussed, supporting the overall utility of this supplemental
      technique to the standard concept mapping methodology. 

PMID- 25064311
TI  - Harvey Cushing, M.D., in his world.
AB  - Harvey Cushing, M.D. (1869-1939), is the acknowledged father of the discipline of
      neurosurgery who inspired others to join him in this new field. He was a prolific
      researcher in the area of human growth disturbances. And he was among the most
      literary of doctors having won the Pulitzer Prize for his two-volume biography of
      his mentor and teacher William Osler, M.D. A driven man, he both inspired and
      intimidated others. This essay explores Cushing's character and background along
      with his relationship to Osler. It seeks to understand why and how he may be
      considered a great figure in spite and because of his demanding and often
      problematic character. It further seeks to place Cushing in the context of the
      transition of American society and American medicine in the latter decades of the
      nineteenth and early decades of the twentieth century. Portions of this essay
      were originally delivered as part of a Grand Rounds presentation for the
      Department of Neurosurgery at the New York Presbyterian Hospital Weill Cornell
      Center. 

PMID- 25064312
TI  - Evangelical Doctors Belief and Practice: A Case Study of the Wellington Christian
      Medical Fellowship, New Zealand 1971-1980.
AB  - This paper presents a critical analysis of the proceedings of the Wellington
      Christian Medical Fellowship (CMF) during the 1970s. Formation of the CMF,
      contemporaneous and historical influences, new traditions, and key events are
      discussed as they arise in the narrative of the case study. Interaction between
      cultural and religious influences on medical practice is a recurring theme
      relevant to other bicultural or multicultural nations with significant health
      inequalities. 

PMID- 25064313
TI  - Aging is something like an opera which can be constructed by many players: an
      interview with Katsuiku Hirokawa.

PMID- 25064316
TI  - Surgical management of pancreatic neoplasms: what's new?
AB  - Pancreatic cancer is the fourth leading cause of cancer deaths in the USA.
      Although some patients will present with premalignant pancreatic lesions (i.e.,
      intraductal papillary mucinous neoplasms) or localized tumors amenable to
      curative resection, the majority of patients will unfortunately present with
      technically unresectable or metastatic disease. This review of the recent medical
      literature will discuss the optimal work-up and management of premalignant
      pancreatic lesions and the surgical management of localized, borderline
      resectable, and locally advanced (i.e., unresectable) pancreatic tumors. It will
      focus on new criteria used to define surgical "resectability," the significance
      and clinical impact of surgical margins, the role of multimodality therapy in the
      management of patients with borderline resectable or locally advanced tumors, the
      role of surgery for local or distant recurrence, and minimally invasive surgical
      approaches. 

PMID- 25064317
TI  - Adolescent rumination syndrome.
AB  - Rumination syndrome is the non-purposeful regurgitation of recently ingested food
      from the stomach to the mouth, where it is either expelled or reswallowed.
      Adolescent rumination syndrome (ARS) is a rare condition of which many physicians
      are unaware. Patients often are misdiagnosed or undergo costly testing, and as a
      result, diagnosis and treatment are often delayed. While ARS is not life
      threatening, it does have medical and emotional effects on the patient and the
      patient's family. Diagnosis of ARS is based upon the Rome III diagnostic
      criteria. Antroduodenal manometry, while not required for a diagnosis, can be
      helpful to confirm the diagnosis. The pathogenesis of this disorder is complex
      and not well understood. However, because of its behavioral component, treatment
      of ARS requires a multidisciplinary approach that includes both medical
      management of symptoms and implementation of strategies that address behavioral,
      psychological, and general quality-of-life components of the disorder. 

PMID- 25064318
TI  - Infectious diarrhea: an overview.
AB  - Diarrheal disease, which is most often caused by infectious pathogens, is a
      significant cause of morbidity and mortality worldwide, especially in children.
      This is particularly true in developing countries. Recent outbreaks of infectious
      diarrhea in developed countries, including the USA, are often attributed to food
      handling and distribution practices and highlight the need for continued
      vigilance in this area. Another common cause of infectious diarrhea, Clostridium
      difficile infection (CDI), has historically been associated with the use of
      antibiotics and exposure to a health-care setting but is now increasingly common
      in the community in persons who lack the typical risk factors. Recent scientific
      advances have also led to new and proposed new therapies for infectious diarrhea,
      including fecal microbiota transplant (FMT) for recurrent C. difficile infection
      (RCDI), probiotics for prevention of antibiotic-associated diarrhea (AAD) and
      CDI, and the use of zinc supplementation in the treatment of acute diarrhea in
      children. Other therapies that have been in use for decades, such as the oral
      rehydration solution (ORS), continue to be the targets of scientific advancement
      in an effort to improve delivery and efficacy. Finally, post-infectious irritable
      bowel syndrome (PI-IBS) is an increasingly recognized occurrence. Attempts to
      understand the mechanism behind this phenomenon are underway and may provide
      insight into potential treatment options. 

PMID- 25064319
TI  - Combined multichannel intraluminal impedance-pH (MII-pH): multicenter report of
      normal values from 117 children.
AB  - Although combined multichannel intraluminal impedance/esophageal pH monitoring
      (MII-pH) has replaced prolonged pH monitoring alone for assessing
      gastroesophageal reflux (GER) in the pediatric population, it does so in the
      absence of reference values for non-acid GER (NAGER). The purpose of this study
      was to identify a normal range of NAGER impedance values for infants and
      children. We evaluated EPM/MII tracings for patients referred for GER assessment
      to Nationwide Children's Hospital (Columbus, OH), Inova Children's Hospital, and
      Hospital Italiano (Buenos Aires, Argentina). We excluded tracings from patients
      who had AGER indices greater than 50 % of the upper end of normal (i.e., >3 % for
      children >12 months and >6 % for infants <= 12 months), had a positive temporal
      association of GER with symptoms, were on anti-reflux medications at the time of
      the study, and/or had a fundoplication prior to the study. We also excluded
      studies with durations shorter than 20 h. Values for NAGER percent time, NAGER
      episode frequency, frequency of proximal NAGER, and mean NAGER duration were
      calculated for upright position, recumbent, and total. Study population consisted
      of 46 infants (20 female [F]/26 male [M], median age 4.8 months [range 3 weeks
      11.9 months]) with a median AGER index of 2.2 % (range 0.0-5.9 %) and 71 children
      (22 F/49 M, median age 7.2 years [range 1.3-17 years]) with a median AGER index
      of 1.1 % (range 0-3.0 %). Data are presented in tables in the text. The results
      of this study provide a range of values characteristic of infants and children
      with normal AGER indices and no positive temporal associations of GER with
      symptoms. These values may be used as references for comparison to identify
      infants and/or children who may be at risk of developing serious clinical
      manifestations due to abnormal patterns of GER.

PMID- 25064320
TI  - Assessment of competence in pediatric gastrointestinal endoscopy.
AB  - Gastrointestinal endoscopy is an invaluable tool for the diagnosis and treatment
      of upper and lower gastrointestinal diseases in children. Pediatric and adult
      endoscopy differ in several respects including differences in procedural
      indications, sedation practices, pre-procedure preparation, equipment, and the
      importance of routine tissue sampling and terminal ileum intubation. In the same
      way that performance of endoscopy in children requires pediatric-specific
      training, assessment of pediatric endoscopists requires an approach that is
      tailored to pediatric practice and the use of assessment methods and measures
      that have been developed and validated specifically within the pediatric context.

PMID- 25064321
TI  - Oxidative stress-mediated activation of extracellular signal-regulated kinase
      contributes to mild cognitive impairment-related mitochondrial dysfunction.
AB  - Mild cognitive impairment (MCI) occurs during the predementia stage of Alzheimer
      disease (AD) and is characterized by a decline in cognitive abilities that
      frequently represents a transition between normal cognition and AD dementia. Its
      pathogenesis is not well understood. Here, we demonstrate the direct consequences
      and potential mechanisms of oxidative stress and mitochondrial dynamic and
      functional defects in MCI-derived mitochondria. Using a cytoplasmic hybrid
      (cybrid) cell model in which mitochondria from MCI or age-matched non-MCI
      subjects were incorporated into a human neuronal cell line depleted of endogenous
      mitochondrial DNA, we evaluated the mitochondrial dynamics and functions, as well
      as the role of oxidative stress in the resultant cybrid lines. We demonstrated
      that increased expression levels of mitofusin 2 (Mfn2) are markedly induced by
      oxidative stress in MCI-derived mitochondria along with aberrant mitochondrial
      functions. Inhibition of oxidative stress rescues MCI-impaired mitochondrial
      fusion/fission balance as shown by the suppression of Mfn2 expression,
      attenuation of abnormal mitochondrial morphology and distribution, and
      improvement in mitochondrial function. Furthermore, blockade of MCI-related
      stress-mediated activation of extracellular signal-regulated kinase (ERK)
      signaling not only attenuates aberrant mitochondrial morphology and function but
      also restores mitochondrial fission and fusion balance, in particular inhibition
      of overexpressed Mfn2. Our results provide new insights into the role of the
      oxidative stress-ERK-Mfn2 signal axis in MCI-related mitochondrial abnormalities,
      indicating that the MCI phase may be targetable for the development of new
      therapeutic approaches that improve mitochondrial function in age-related
      neurodegeneration.

PMID- 25064323
TI  - Collateral sensitivity: ABCG2-overexpressing cells are more vulnerable to
      oxidative stress.
AB  - Multidrug resistance (MDR), which is the main obstacle to cancer chemotherapy, is
      mainly due to overexpression of ATP-binding cassette (ABC) transporters,
      especially ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP). A novel idea
      to overcome MDR is that of collateral sensitivity, i.e., finding a treatment to
      which cells overexpressing ABC transporters are more sensitive than cells that do
      not overexpress them. In this study we demonstrate for the first time that MDCKII
      BCRP cells, overexpressing ABCG2, are more vulnerable to exogenous oxidative
      stress induced by several oxidants, viz. paraquat, menadione, hydrogen peroxide,
      tert-butylperoxide, and 2,2-azobis(2-methylpropionamidine) dihydrochloride.
      MDCKII-BCRP cells have significantly decreased glutathione level and decreased
      activities of glutathione S-transferase and glutathione reductase, which may
      underlie their augmented vulnerability to oxidative stress. These results suggest
      the possibility of using agents that induce oxidative stress to selectively kill
      cells overexpressing BCRP.

PMID- 25064322
TI  - Glutathione sulfinamide serves as a selective, endogenous biomarker for nitroxyl
      after exposure to therapeutic levels of donors.
AB  - Nitroxyl (HNO) donors exhibit promising pharmacological characteristics for
      treatment of cardiovascular disorders, cancer, and alcoholism. However, whether
      HNO also serves as an endogenous signaling agent is currently unknown, largely
      because of the inability to selectively and sensitively detect HNO in a cellular
      environment. Although a number of methods to detect HNO have been developed
      recently, sensitivity and selectivity against other nitrogen oxides or biological
      reductants remain problematic. To improve selectivity, the electrophilic nature
      of HNO has been harnessed to generate modifications of thiols and phosphines that
      are unique to HNO, especially compared to nitric oxide (NO). Given high
      bioavailability, glutathione (GSH) is expected to be a major target of HNO. As a
      result, the putative selective product glutathione sulfinamide (GS(O)NH2) may
      serve as a high-yield biomarker of HNO production. In this work, the formation of
      GS(O)NH2 after exposure to HNO donors was investigated. Fluorescent labeling
      followed by separation and detection using capillary zone electrophoresis with
      laser-induced fluorescence allowed quantitation of GS(O)NH2 with nanomolar
      sensitivity, even in the presence of GSH and derivatives. Formation of GS(O)NH2
      was found to occur exclusively upon exposure of GSH to HNO donors, thus
      confirming selectivity. GS(O)NH2 was detected in the lysate of cells treated with
      low-micromolar concentrations of HNO donors, verifying that this species has
      sufficient stability to server as a biomarker of HNO. Additionally, the
      concentration-dependent formation of GS(O)NH2 in cells treated with an HNO donor
      suggests that the concentration of GS(O)NH2 can be correlated to intracellular
      levels of HNO. 

PMID- 25064324
TI  - Selenium prevents downregulation of antioxidant selenoprotein genes by
      methylmercury.
AB  - Selenium (Se) is an essential nutrient required by Se-dependent proteins, termed
      selenoproteins. The selenoprotein family is small but diverse and includes key
      proteins in antioxidant, redox signaling, thyroid hormone metabolism, and protein
      folding pathways. Methylmercury (MeHg) is a toxic environmental contaminant that
      affects seafood safety. Selenium can reduce MeHg toxicity, but it is unclear how
      selenoproteins are affected in this interaction. In this study we explored how Se
      and MeHg interact to affect the mRNA expression of selenoprotein genes in whole
      zebrafish (Danio rerio) embryos. Embryos were obtained from adult zebrafish fed
      MeHg with or without elevated Se in a 2*2 factorial design. The embryo mRNA
      levels of 30 selenoprotein genes were then measured. These genes cover most of
      the selenoprotein families, including members of the glutathione peroxidase
      (GPX), thioredoxin reductase, iodothyronine deiodinase, and methionine sulfoxide
      reductase families, along with selenophosphate synthetase 2 and selenoproteins H,
      J-P, T, W, sep15, fep15, and fam213aa. GPX enzyme activity and larval locomotor
      activity were also measured. We found that around one-quarter of the
      selenoprotein genes were downregulated by elevated MeHg. These downregulated
      genes were dominated by selenoproteins from antioxidant pathways that are also
      susceptible to Se-deficiency-induced downregulation. MeHg also decreased GPX
      activity and induced larval hypoactivity. Elevated Se partially prevented MeHg
      induced disruption of selenoprotein gene mRNA levels, GPX activity, and larval
      locomotor activity. Overall, the MeHg-induced downregulation and subsequent
      rescue by elevated Se levels of selenogenes regulated by Se status suggest that
      Se deficiency is a contributing factor to MeHg toxicity.

PMID- 25064325
TI  - Outcome of the pivotal study of the Aptus endovascular abdominal aortic aneurysms
      repair system.
AB  - OBJECTIVE: Endovascular treatment of abdominal aortic aneurysm (AAA) is
      associated with benefits over open surgery, yet limitations remain with current
      endovascular devices. This study was performed to assess outcomes of AAA repair
      with the Aptus endograft and EndoAnchors (Aptus Endosystems, Sunnyvale, Calif).
      METHODS: This prospective, multicenter, single-arm investigational device
      exemption trial was conducted at 25 sites in the United States. A total of 155
      patients were enrolled in the trial (mean age, 73 +/- 8 years; male, 93.5%; mean
      AAA diameter, 53.6 +/- 7.9 mm). The Aptus endograft is a two-component system: a
      multilumen, modular endograft with two docking limbs (Aptus Endograft System) and
      the Heli-FX Aortic Securement System comprising an electronically controlled
      applier (Heli-FX Applier) with helical EndoAnchors provided in a cassette and a
      deflectable sheath (Heli-FX Guide) designed for delivery of the applier to the
      target location for EndoAnchor implantation. The main eligibility criteria
      included proximal neck length of >=12 mm, diameter of 19 to 29 mm, and infrarenal
      angulation of <=60 degrees. The primary safety end point was freedom from major
      adverse events at 30 days, and the primary effectiveness end point was successful
      aneurysm treatment at 12 months. Thrombus-related events (TRE) were defined as
      limb occlusion or thromboembolism from the endograft. Subjects were observed for
      a median of 4.2 years, with imaging end points analyzed by a core laboratory and
      adverse events adjudicated by a clinical events committee. RESULTS: Among 155
      enrolled subjects, 153 (98.7%) underwent successful implantation of the Aptus
      endograft and a median of five EndoAnchors; two subjects were converted to open
      surgical repair during the initial procedure. Overall, the primary safety and
      effectiveness end points were met in 98.1% and 97.4% of the subjects,
      respectively. Aneurysm-related mortality was 0.6%, with one postdischarge cardiac
      death 18 days after implantation. There were no AAA ruptures. There were no
      fractures of stents or EndoAnchors. There was one type I endoleak and one type
      III endoleak. Stent graft migration was noted in five subjects, none associated
      with sac enlargement, type I endoleak, or EndoAnchor dislocation from the
      endograft. AAA sac shrinkage of >=5 mm at 1, 2, and 3 years was observed in
      60.3%, 72.9%, and 81.7%, respectively. Sixty-one subjects (39.4%) experienced 113
      TRE, associated with 80 reinterventions (in 58 subjects) unassociated with limb
      loss or death. A root cause analysis of TRE identified small, out-of
      specification docking limbs with graft infolding and high local shear, resulting
      in thrombus formation within the endograft with subsequent distal embolization in
      some cases. CONCLUSIONS: Early results of the Aptus endograft trial met its
      safety and effectiveness end points; however, a high rate of TRE was observed
      because of manufacturing discrepancies. The findings confirm a low rate of type I
      and type III endoleaks, migration, and non-TRE reintervention with a high rate of
      aneurysm sac regression during midterm follow-up.

PMID- 25064326
TI  - Invited commentary.

PMID- 25064327
TI  - Asymptomatic aortic occlusion secondary to abdominal aortic aneurysm.

PMID- 25064328
TI  - Transiliac wing alternate route bypass for infected groin vascular graft.

PMID- 25064329
TI  - Extending life or prolonging death: when is enough actually too much?

PMID- 25064330
TI  - Peripheral occlusive disease may provide the highest hospital margins despite
      rising costs.
AB  - OBJECTIVE: The objective of this study was to review vascular surgical financial
      trends in a tertiary care setting and to evaluate the impact of a vascular
      program within a health care system in the face of lower reimbursements and
      rising costs. METHODS: With use of Current Procedural Terminology codes and
      diagnosis-related groups, vascular categories of aortic disease, cerebrovascular
      disease, and peripheral occlusive disease (POCD) were identified at an academic
      tertiary health care center. Hospital margins were calculated for each of the
      defined categories by Health Quest cost accounting data cross-walked with Current
      Procedural Terminology codes, date of service, and admitting physician for each
      year from 2010 to 2012. RESULTS: All categories realized volume growth and a
      positive margin for the hospital. In comparison of 2010 and 2012, aortic cases
      showed an overall volume growth of 19%, revenue increase of 31%, and cost
      increase of 54%, resulting in an overall margin decrease of 7%. Cerebrovascular
      cases showed a 30% increase in volume growth, revenue increase of 13%, and cost
      increase of 5%, resulting in a margin increase of 18%. POCD cases showed overall
      volume growth of 35%, revenue increase of 37%, cost increase of 54%, and a margin
      increase of 15%. The margin for POCD exceeded the margin for aortic and
      cerebrovascular cases combined by 77%. CONCLUSIONS: In evaluating a vascular
      program's fiscal viability, volume-driven POCD was the only category producing
      growing hospital margins in the face of significant cost increases.

PMID- 25064331
TI  - The need for a validated pathway for the diagnosis and management of prosthetic
      vascular graft infection.

PMID- 25064332
TI  - Lipid metabolites as markers of fattening rate in a non-migratory passerine:
      effects of ambient temperature and individual variation.
AB  - Plasma lipid metabolites triglycerides (TRIG) and glycerol (GLY) are used as
      indicators of fattening rate and nutritional condition in migratory birds.
      Requiring only one blood sample, they could also be used for studying daily and
      seasonal fattening rates in relation with habitat quality or weather variations
      in species wintering in cold climates. Using black-capped chickadees exposed to
      three experimental temperatures (0  degrees C, 15  degrees C, and 30  degrees C),
      the goal of this experiment was to determine the relationship between plasma
      levels of TRIG and GLY and fattening rate measured over periods from a few hours
      to the previous two days. Results showed that birds maintained in the cold had
      metabolite levels 39-81% higher than those at thermoneutrality, likely reflecting
      the size of their fat reserves, and that TRIG and total GLY were highly
      correlated across treatments. Fattening rate was also higher at 0  degrees C
      (+35%) and 30  degrees C (+24%) relative to that measured at 15  degrees C and,
      as expected, was positively correlated with metabolite levels across treatments.
      However, despite fattening rates similar to that observed at the other
      temperatures, the relationships were uncoupled at 30  degrees C, implying that
      the technique may not be easily applicable at temperatures within or close to
      thermoneutrality. We also found a strong individual effect in the relationships
      between fattening rate and TRIG levels, suggesting high individual consistency in
      these parameters in conditions of unrestricted food access such as in captivity.
      Our study confirms that plasma TRIG and GLY levels can be used as relative
      indexes of condition and fattening rates in wintering passerines.

PMID- 25064333
TI  - Evaluation of marine sediments as microbial sources for methane production from
      brown algae under high salinity.
AB  - Various marine sediments were evaluated as promising microbial sources for
      methane fermentation of Saccharina japonica, a brown alga, at seawater salinity.
      All marine sediments tested produced mainly acetate among volatile fatty acids.
      One marine sediment completely converted the produced volatile fatty acids to
      methane in a short period. Archaeal community analysis revealed that acetoclastic
      methanogens belonging to the Methanosarcina genus dominated after cultivation.
      Measurement of the specific conversion rate at each step of methane production
      under saline conditions demonstrated that the marine sediments had higher
      conversion rates of butyrate and acetate than mesophilic methanogenic granules.
      These results clearly show that marine sediments can be used as microbial sources
      for methane production from algae under high-salt conditions without dilution. 

PMID- 25064334
TI  - Thermogravimetric analysis and fast pyrolysis of Milkweed.
AB  - Pyrolysis of Milkweed was carried out in a thermogravimetric analyzer and a
      bubbling fluidized bed reactor. Total liquid yield of Milkweed pyrolysis was
      between 40.74% and 44.19 wt% between 425  degrees C and 550  degrees C. The gas
      yield increased from 27.90 wt% to 33.33 wt% with increasing reaction temperature.
      The higher heating values (HHV) of the Milkweed bio-oil were relatively high
      (30.33-32.87 MJ/kg) and varied with reaction temperature, feeding rate and
      fluidization velocity. The selectivity for CO2 was highest within non-condensable
      gases, and the molar ratio of CO2/CO was about 3 at the different reaction
      conditions. The (13)C NMR analysis, of the bio-oil showed that the relative
      concentration carboxylic group and its derivatives was higher at 425  degrees C
      than 475  degrees C, which resulted in slightly higher oxygen content in bio-oil.
      The pH of aqueous phase obtained at 475  degrees C was 7.37 which is the highest
      reported for any lignocellulosic biomass pyrolysis oils.

PMID- 25064335
TI  - Enhanced dewaterability of anaerobically digested sewage sludge using
      Acidithiobacillus ferrooxidans culture as sludge conditioner.
AB  - Role of Acidithiobacillus ferrooxidans culture in bioacidification and
      dewaterability of anaerobically digested sewage sludge (ADS) was investigated. A.
      ferrooxidans culture grown in 9K medium along with Fe(2+) produced iron
      flocculant containing, secondary iron minerals and biopolymeric substances as
      confirmed by FT-IR, XRD, and SEM-EDX. Bioacidification of ADS was performed using
      10% (v/v) A. ferrooxidans culture, isolated cells and cell-free culture filtrate;
      and dewaterability was assessed using the capillary suction time (CST) and
      specific resistance to filtration (SRF). Isolated bacterial cells significantly
      (P<0.05) reduced the sludge dewaterability when supplemented with Fe(2+) while
      the whole culture and cell-free filtrate rapidly acidified the sludge without
      Fe(2+) and showed significant reduction of CST (71.3-73.5%) and SRF (84-88%).
      Results clearly indicated that the culture and filtrate of the A. ferrooxidans
      facilitated rapid sludge dewaterability while the cells supplemented with Fe(2+)
      also enhanced dewaterability but required 2-4 days.

PMID- 25064336
TI  - Optimized membrane process to increase hemicellulosic ethanol production from
      pretreated rice straw by recombinant xylose-fermenting Saccharomyces cerevisiae.
AB  - Oligomeric sugars in the liquid fraction of hot water-pretreated rice straw are
      more amenable to membrane process than monomeric sugars, as lower pressure is
      required. Following membrane process was employed: nanofiltration (NF)
      concentration -> (dilution -> NF concentration) * 2 times -> enzymatic hydrolysis
      (EH) -> ultrafiltration (UF) permeation [ IMPLICATION: NF for recovery of
      oligomeric sugars, dilution and NF for removal of low molecular weight
      fermentation inhibitors, UF for removal of high molecular weight fermentation
      inhibitors and recovery of monomeric sugars after EH]. This process provided the
      liquid fraction containing 111.4 g L(-1) of sugars, corresponding to 681.0mM as
      monomeric sugars, from the original liquid fraction (181.1mM monomeric sugars).
      Concentrations of low molecular weight fermentation inhibitors, acetic and formic
      acids, were decreased to 24% and 48%, respectively. Xylose-fermenting recombinant
      Saccharomyces cerevisiae produced 34.5 +/- 2.2 g L(-1) ethanol from the 0.8 times
      liquid fraction (76% of theoretical yield).

PMID- 25064337
TI  - Development of an indirect immunofluorescence technique for the evaluation of
      generated antibody titers against Erysipelothrix rhusiopathiae in captive
      bottlenose dolphins (Tursiops truncatus).
AB  - Erysipelothrix rhusiopathiae is the causative agent of erysipelas, a disease of
      many mammalian and avian species, mainly swine and turkeys. In cetaceans,
      erysipelas is considered to be the most common infection in juvenile individuals,
      which have not been vaccinated. Moreover, the disease manifest in both forms, the
      dermatologic and the acute septicemic forms, has been reported in various species
      of dolphins and whales. It is difficult to diagnose erysipelas by currently
      available approaches. Moreover, it is mainly based on culture methods and also
      PCR methods, which are currently being developed. At the present stage,
      prophylactic approaches are based on antibiotic therapy and vaccination mostly
      with porcine erysipelas vaccines. In the present study, an Indirect Immuno
      Fluorescence method for the detection of dolphin antibodies levels against E.
      rhusiopathiae was developed and applied in two different groups of captive
      bottlenose dolphins (Tursiops truncatus) from Loro Parque (Tenerife, Canary
      Islands, Spain) and L'Oceanografic de Valencia (Valencia, Spain) in order to
      check the tittering levels of antibodies after application of porcine erysipelas
      vaccines in the studied dolphins. 

PMID- 25064338
TI  - Decreasing nicotinic receptor activity and the spatial learning impairment caused
      by the NMDA glutamate antagonist dizocilpine in rats.
AB  - Nicotinic systems have been shown by a variety of studies to be involved in
      cognitive function. Nicotinic receptors have an inherent property to become
      desensitized after activation. The relative role of nicotinic receptor activation
      vs. net receptor inactivation by desensitization in the cognitive effects of
      nicotinic drugs remains to be fully understood. In these studies, we tested the
      effects of the alpha7 nicotinic receptor antagonist methyllycaconitine (MLA), the
      alpha4beta2 nicotinic receptor antagonist dihydro-beta-erythroidine (DHbetaE),
      the nonspecific nicotinic channel blocker mecamylamine and the alpha4beta2
      nicotinic receptor desensitizing agent sazetidine-A on learning in a repeated
      acquisition test. Adult female Sprague-Dawley rats were trained on a repeated
      acquisition learning procedure in an 8-arm radial maze. MLA (1-4mg/kg), DHbetaE
      (1-4mg/kg), mecamylamine (0.125-0.5mg/kg) or sazetidine-A (1 and 3mg/kg) were
      administered in four different studies either alone or together with the NMDA
      glutamate antagonist dizocilpine (0.05 and 0.10mg/kg). MLA significantly
      counteracted the learning impairment caused by dizocilpine. The overall choice
      accuracy impairment caused by dizocilpine was significantly attenuated by co
      administration of DHbetaE. Low doses of the non-specific nicotinic antagonist
      mecamylamine also reduced dizocilpine-induced repeated acquisition impairment.
      Sazetidine-A reversed the accuracy impairment caused by dizocilpine. These
      studies provide evidence that a net decrease in nicotinic receptor activity can
      improve learning by attenuating learning impairment induced by NMDA glutamate
      blockade. This adds to evidence in cognitive tests that nicotinic antagonists can
      improve cognitive function. Further research characterizing the efficacy and
      mechanisms underlying nicotinic antagonist and desensitization induced cognitive
      improvement is warranted. 

PMID- 25064339
TI  - Doliroside A attenuates monosodium urate crystals-induced inflammation by
      targeting NLRP3 inflammasome.
AB  - Our previous study demonstrates that Dolichos falcata Klein (DF) ameliorates the
      gouty arthritis induced by monosodium urate (MSU) crystals, and one of the active
      components, doliroside A, contributed to the anti-gouty arthritis effect of DF
      according to the in vitro study. However, there is still little known about the
      potential beneficial effects and possible mechanism of action of doliroside A on
      gouty arthritis. Here, we investigated the underlying mechanism of action of
      doliroside A in vitro and the anti-inflammatory effects of doliroside A in vivo.
      Bone-marrow-derived macrophages were treated with doliroside A before or after
      lipopolysaccharide (LPS) and then stimulated with MSU crystals, nigericin and
      adenosine triphosphate (ATP). The expressions of proteins related to activation
      of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3)
      inflammasome were analyzed. The results manifested that doliroside A (15, 30, 45
      and 60 MUM) suppressed both LPS-induced priming and inflammasome activation in
      macrophages. Moreover, doliroside A was administered to the rats treated by MSU
      crystals. The results demonstrated that doliroside A (10, 20 and 40 mg/kg)
      ameliorated the symptoms of gouty arthritis, decreased the levels of pro
      inflammatory cytokines, and inhibited the expressions of caspase-1 and pro
      interleukin-1beta (pro-IL-1beta) proteins in MSU crystals-treated rats. These
      findings indicate that doliroside A exhibits a prominent effect on ameliorating
      gouty arthritis induced by MSU crystals. The action of doliroside A on gouty
      arthritis exerts via inhibiting the activation of caspase-1 and IL-1beta
      secretion by affecting both LPS-induced priming and inflammasome activation.

PMID- 25064340
TI  - Levocetirizine ameliorates high fructose diet-induced insulin resistance,
      vascular dysfunction and hepatic steatosis in rats.
AB  - This study investigates the possible protective effects of levocetirizine against
      fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction,
      in comparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley
      rats (150-200 g) were divided into 4 groups. Three groups were fed on high
      fructose diets (HFD) containing 60% w/w fructose, while the fourth control group
      was fed on standard laboratory food for 8 weeks. AUCOGTT, AUCITT, fasting
      glucose, HOMA-IR, hepatic glutathione (GSH) and malondialdehyde (MDA) levels,
      serum total cholesterol, LDL-C, C-reactive protein (CRP) level and lactate
      dehydrogenase (LDH) activity and liver steatosis scores were significantly higher
      in HFD group compared to control group. Moreover, body weight gain, food intake,
      feeding efficiency, HOMA-beta, Emax and pEC50 of acetylcholine-induced
      relaxations of aortic rings and hepatic superoxide dismutase (SOD) activity were
      significantly lower in HFD group than in control group. Treatment with
      levocetirizine caused significant decreases in AUCOGTT, AUCITT, HOMA-IR, hepatic
      GSH and MDA levels and serum CRP level and LDH activity and significant increases
      in hepatic SOD activity and HOMA-beta when compared with the HFD group. Although
      levocetirizine failed to alter TC and LDL-C levels, it produced a significant
      increase in HDL-C level relative to control group. Levocetirizine was also able
      to improve acetylcholine-induced relaxations of aortic rings, indicating a
      protective effect against insulin resistance-induced endothelial damage
      comparable to that offered by pioglitazone. Moreover, levocetirizine
      substantially attenuated insulin resistance-associated liver macrovesicular
      steatosis. These findings demonstrate that levocetirizine ameliorates insulin
      resistance, improves glucose tolerance and attenuates insulin resistance-linked
      hepatic steatosis and vascular damage.

PMID- 25064341
TI  - Protective effect of mangiferin against lipopolysaccharide-induced depressive and
      anxiety-like behaviour in mice.
AB  - Numerous studies have demonstrated that inflammation, oxidative stress and
      altered level of neurotrophins are involved in the pathogenesis of depressive
      illness. Mangiferin, a C-glucosylxanthone is abundant in the stem and bark of
      Mangifera indica L. The compound has been shown to possess antioxidant, anti
      inflammatory and immunomodulatory activities. The present study was performed to
      investigate the effect of mangiferin pretreatment on lipopolysaccharide-induced
      increased proinflammatory cytokines, oxidative stress and neurobehavioural
      abnormalities. Mice were challenged with lipopolysaccharide (0.83 mg/kg, i.p.)
      after 14 days of mangiferin (20 and 40 mg/kg, p.o.) pretreatment. Mangiferin
      pretreatment significantly ameliorated the anxiety-like behaviour as evident from
      the results of an elevated plus maze, light-dark box and open field test.
      Mangiferin pretreatment also improved the anhedonic behaviour as revealed by
      sucrose preference test and increased social interaction time. It also prevented
      the lipopolysaccharide-evoked depressive-like effect by reducing the immobility
      time in forced swim and tail suspension test. Lipopolysaccharide-induced elevated
      oxidative stress was decreased with mangiferin pretreatment due to its potential
      to increase reduced glutathione concentration, Superoxide dismutase and catalase
      activity and decrease lipid peroxidation and nitrite level in the hippocampus as
      well as in the prefrontal cortex. Mangiferin pretreatment also attenuated
      neuroinflammation by reducing the interleukin-1 beta (IL-1beta) level in
      hippocampus and prefrontal cortex. In conclusion, our results demonstrated that
      mangiferin possessed antidepressant and anti-anxiety properties due to its
      ability to attenuate IL-1beta level and oxidative stress evoked by
      intraperitoneal administration of lipopolysaccharide. Mangiferin may be a
      potential therapeutic agent for the treatment of depressive and anxiety illness.

PMID- 25064342
TI  - Fisetin improves glucose homeostasis through the inhibition of gluconeogenic
      enzymes in hepatic tissues of streptozotocin induced diabetic rats.
AB  - Liver plays a vital role in blood glucose homeostasis. Recent studies have
      provided considerable evidence that hepatic glucose production (HGP) plays an
      important role in the development of fasting hyperglycemia in diabetes. From this
      perspective, diminution of HGP has certainly been considered for the treatment of
      diabetes. In the present study, we have analyzed the modulatory effects of
      fisetin, a flavonoid of strawberries, on the expression of key enzymes of
      carbohydrate metabolism in STZ induced experimental diabetic rats. The
      physiological criterions such as food and fluid intake were regularly monitored.
      The levels of blood glucose, plasma insulin, hemoglobin and glycosylated
      hemoglobin were analyzed. The mRNA and protein expression levels of gluconeogenic
      genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase
      (G6Pase) were determined by immunoblot as well as PCR analysis. Diabetic group of
      rats showed significant increase in food and water intake when compared with
      control group of rats. Upon oral administration of fisetin as well as gliclazide
      to diabetic group of rats, the levels were found to be decreased. Oral
      administration of fisetin (10 mg/kg body weight) to diabetic rats for 30 days
      established a significant decline in blood glucose and glycosylated hemoglobin
      levels and a significant increase in plasma insulin level. The mRNA and protein
      expression levels of gluconeogenic genes, such as phosphoenolpyruvate
      carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), were decreased in liver
      tissues upon treatment with fisetin. The results of the present study suggest
      that fisetin improves glucose homeostasis by direct inhibition of gluconeogenesis
      in liver.

PMID- 25064343
TI  - Anti-angiogenic effect of auranofin on HUVECs in vitro and zebrafish in vivo.
AB  - Angiogenesis plays an essential role in many physiological and pathological
      processes. Auranofin (Ridaura(r)), an important gold(I) complex, is used to treat
      rheumatoid arthritis. However, the effect of auranofin on blood vessel formation
      is still unclear. In this study, we investigated the anti-angiogenic activity of
      auranofin on human umbilical vein endothelial cells (HUVEC) in vitro and
      zebrafish in vivo. Our results showed that auranofin could inhibit the
      proliferation, migration and tube formation of HUVECs and disrupted the formation
      of intersegmental vessels and the subintestinal vessels of zebrafish embryos.
      Auranofin inhibited the phosphorylation of vascular endothelial growth factor 2
      (p-VEGFR2) on HUVECs and suppressed the vascular endothelial growth factor (VEGF)
      signaling pathway (vegfa, flt-1, kdr) but not thioredoxin reductase (TrxR) on
      zebrafish. Our study suggested that auranofin might serve as a potential anti
      angiogenic compound candidate.

PMID- 25064344
TI  - Impact of left atrial appendage ridge ablation on the complex fractionated
      electrograms in persistent atrial fibrillation.
AB  - BACKGROUND: The left atrial appendage (LAA) is a possible key contributor to the
      maintenance of persistent atrial fibrillation (PsAF). The effect of LAA ostial
      ablation on global left atrial higher-frequency sources remains unclear. METHODS:
      Complex fractionated electrograms (CFEs) and dominant frequency (DF) maps
      acquired with a NavX system in 58 PsAF patients were enrolled and examined before
      and after LAA posterior ridge ablation, which followed a stepwise linear
      ablation. RESULTS: High-density left atrial mapping identified continuous CFE
      sites in 50 % and high-DFs (>= 8 Hz) in 53 % of patients at the LAA posterior
      ridge. In 44 patients in whom AF persisted despite pulmonary vein isolation (PVI)
      and linear ablation, LAA ablation significantly increased the mean CFE cycle
      length from 98 +/- 29 to 108 +/- 30 ms (P<0.0001) and decreased DF from 6.1 +/-
      0.8 to 5.9 +/- 0.8 Hz (P<0.005) within the coronary sinus (CS). A multivariate
      analysis showed single-procedure failures could be predicted by the left atrial
      volume index and absence of continuous CFEs at the LAA posterior ridge region.
      The percent decrease in the global left atrial DF after LAA posterior ridge
      ablation was significantly lower in the patients with than in those without an
      enlarged left atrium (LA) (>90 mL/m(2)) (median 0 vs 4.8 %; P<0.01) and
      significantly lower in the patients with than in those without the absence of
      continuous CFEs in the LAA posterior ridge region (median 0.6 vs 4.8 %; P<0.05).
      CONCLUSION: These findings suggested that an approach incorporating an LAA
      posterior ridge ablation was effective in modifying higher-frequency sources in
      the global LA in PsAF patients, but a lesser effect was documented in patients
      with electroanatomical remodeling of the LA.

PMID- 25064345
TI  - The synthesis and activities of novel mononuclear or dinuclear cyclen complexes
      bearing azole pendants as antibacterial and antifungal agents.
AB  - A series of novel compounds containing 1,4,7,10-tetraazacyclododecane and azoles
      were synthesized and characterized by (1)H NMR, MS and elemental analysis.
      Bioactive assay manifested that some target compounds, such as 11a, 11b and 11d,
      displayed good and broad spectrum antimicrobial activities with relative low MIC
      values against most of tested strains. These dinuclear complexes gave comparable
      or even better antimicrobial efficiencies than the reference drugs Fluconazole
      and Chloromycin. The result showed that the metal ions were the key factors to
      enhance the antimicrobial activities for mononuclear or dinuclear complexed in
      varying degrees. The interaction evaluation of compound 11b with bovine serum
      albumin (BSA) as an example was tested by fluorescence method. The thermodynamic
      parameters indicated that the hydrogen bonds and van der waals forces played the
      major roles in the strong association between dinuclear compound and BSA. The CCK
      8 tests also confirmed the safeties of these dinuclear compounds in vitro.

PMID- 25064346
TI  - 2-(4-Chlorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazoles: synthesis, cytotoxic
      activity and mechanism of action.
AB  - The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted
      imidazo[2,1-b][1,3,4]thiadiazoles against different human and murine cancer cell
      lines is reported. Among the tested compounds, two derivatives namely 2-(4
      chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5
      carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1
      b][1,3,4]thiadiazol-5-yl thiocyanate 5i emerged as the most potent against all
      the cell lines. To investigate the mechanism of action, we selected compounds 4i
      for cell cycle study, analysis of mitochondrial membrane potential and Annexin V
      FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i
      induced cytotoxicity by inducing apoptosis without arresting the cell cycle. 

PMID- 25064347
TI  - Discovery of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives as
      novel VEGFR-2 kinase inhibitors.
AB  - Inhibition of the VEGF signaling pathway has become a valuable approach in the
      treatment of cancers. In this work, a series of N-(2-phenyl-1H-benzo[d]imidazol-5
      yl)quinolin-4-amine derivatives were designed and identified as potent inhibitors
      of VEGFR-2 (KDR) kinase. These compounds with quinoline scaffold and
      benzimidazole moiety were synthesized and their biological activities against
      VEGFR-2 and two human cancer cell lines were evaluated. Among them, compound 7s
      exhibited the most potent inhibitory activity against VEGFR-2 with IC50 of 0.03
      MUM and it also showed the highest anticancer activity against the tested cancer
      cell lines with IC50 of 1.2 MUM against MCF-7 and 13.3 MUM against Hep-G2.
      Docking simulation supported the initial pharmacophoric hypothesis and suggested
      a common mode of interaction at the ATP-binding site of VEGFR-2, which
      demonstrates that compound 7s is a potential agent for cancer therapy deserving
      further researching.

PMID- 25064348
TI  - Synthesis and evaluation of the cytotoxic activity of 1,2-furanonaphthoquinones
      tethered to 1,2,3-1H-triazoles in myeloid and lymphoid leukemia cell lines.
AB  - Leukemia is the most common blood cancer, and its development starts at diverse
      points, leading to distinct subtypes that respond differently to therapy. This
      heterogeneity is rarely taken into account in therapies, so it is still essential
      to look for new specific drugs for leukemia subtypes or even for therapy
      resistant cases. Naphthoquinones (NQ) are considered privileged structures in
      medicinal chemistry due to their plethora of biological activities, including
      antimicrobial and anticancer effects. Nitrogen-containing heterocycles such as
      1,2,3-1H-triazoles have been identified as general scaffolds for generating
      glycosidase inhibitors. In the present study, the NQ and 1,2,3-1H-triazole cores
      have been combined to chemically synthesize 18 new 1,2-furanonaphthoquinones
      tethered to 1,2,3-1H-triazoles (1,2-FNQT). Their cytotoxicities were evaluated
      against four different leukemia cell lines, including MOLT-4 and CEM (lymphoid
      cell lines) and K562 and KG1 (myeloid cell lines), as well as normal human
      peripheral blood mononucleated cells (PBMCs). The new 1,2-FNQT series showed high
      cytotoxic potential against all leukemia cell lines tested, and some compounds
      (12o and 12p) showed even better results than the classical therapeutic compounds
      such as doxorubicin or cisplatin. Others compounds, such as 12b, are promising
      because of their high selectivity against lymphoblastic leukemia and their low
      activity against normal hematopoietic cells. The cells of lymphoid origin (MOLT
      and CEM) were generally more sensitive than the myeloid cell lines to this series
      of compounds, and most of the compounds that showed the highest cytotoxicity were
      similarly active against both cell lines.

PMID- 25064349
TI  - New imidazo[1,2-b]pyrazoles as anticancer agents: synthesis, biological
      evaluation and structure activity relationship analysis.
AB  - Synthesis and functionalization strategies of the imidazo[1,2-b]pyrazole core
      were developed giving a rapid access to three series of novel imidazo[1,2
      b]pyrazole type derivatives: C-2/C-6/C-7 trisubstituted, C-2/C-3/C-6
      tri(hetero)arylated and C-2/C-3/C-6/C-7 tetrasubstituted imidazo[1,2-b]pyrazoles.
      39 of the synthetized products were evaluated for in vitro anticancer activity
      using the MTT colorimetric assay against 5 human and 1 murine cancer cell lines.
      Promising in vitro growth inhibitory activities were exhibited by some of the
      target compounds. Of the 39 evaluated products, 4 displayed an IC50 <= 10 MUM in
      the 6 cell lines analyzed (compounds 4d, 4g, 9a, 11a). A structure activity
      relationship analysis is also reported in this paper.

PMID- 25064350
TI  - Discovery of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives as potent
      anticancer and antimicrobial agents and screening of anti-diabetic activity:
      synthesis and in vitro biological evaluation. Part 1.
AB  - Series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate (DDTD) derivatives:
      azomethines of DDTD (2a-l) have been synthesized and screened for their
      anticancer, antimicrobial and anti-diabetic activities. The novel synthesized
      compounds were characterized by (1)H, (13)C NMR, MS and FT-IR analyses. All
      compounds were evaluated for their antiproliferative activity against three types
      of cancer cell line such as T47D and MCF-7 (human breast cancer), Hela (human
      cervical cancer) and Ishikawa (human endometrial cancer) lines. The results
      showed that most compounds exhibited significant antiproliferative activity
      against breast cancer cells. The majority of azomethines DDTD influenced strongly
      against breast cancer cells T47D and MCF-7, among them compounds 2b (2.3 MUM), 2c
      (12.1 MUM), 2e (13.2 MUM), 2i (14.9 MUM), 2j (16.0 MUM), 2k (7.1 MUM), 2l (8.6
      MUM) manifest potent anticancer activity against cancer cell T47D than
      Doxorubicin (DOX, 15.5 MUM). Compound 2j has shown potent activity on all three
      types of cancer cells concurrently and IC50 values were considerably low in
      comparison with positive control DOX. In addition, all compounds were tested for
      antimicrobial activity against Staphylococcus aureus ATCC 6538 (Gram positive
      bacteria), Escherichia coli ATCC 11229 (Gram negative bacteria) and Candida
      albicans ATCC 10231 (Fungi) strains and 2j which contains in the ring
      nitrofurfural fragment, showed the highest effect on the three species of
      microbial pathogens simultaneously. Some compounds induced enzymatic inhibition
      in a concentration-dependent manner on PTP-1B inhibitor.

PMID- 25064351
TI  - Synthesis and biological evaluation of novel 6-chloro-quinazolin derivatives as
      potential antitumor agents.
AB  - Series of novel derivatives of 6-chloro-quinazolin, which this moiety was linked
      to a 1,5-diaryl-1,4-pentadien-3-one system, have been synthesized and tested for
      their antitumor activities in vitro against a panel of three human cancer cell
      lines (MGC-803, Bcap-37, and PC3 cells). Bioassay results indicated that most of
      the prepared compounds demonstrated good activities against various cancer cells.
      6-chloro-quinazolin derivatives 5a and 5f were the most active members in this
      study, and experimental results of fluorescent staining and flow cytometry
      analysis revealed that they could induce apoptosis in MGC-803 and Bcap-37 cells,
      with apoptosis ratios of 31.7% and 21.9% at 24 h of treatment at 10 MUM in MGC
      803 cells. Those two quinazoline derivatives could be considered as useful
      templates for future development to obtain more potent antitumor agents.

PMID- 25064352
TI  - Marine actinobacteria associated with marine organisms and their potentials in
      producing pharmaceutical natural products.
AB  - Actinobacteria are ubiquitous in the marine environment, playing an important
      ecological role in the recycling of refractory biomaterials and producing novel
      natural products with pharmic applications. Actinobacteria have been detected or
      isolated from the marine creatures such as sponges, corals, mollusks, ascidians,
      seaweeds, and seagrass. Marine organism-associated actinobacterial 16S rRNA gene
      sequences, i.e., 3,003 sequences, deposited in the NCBI database clearly revealed
      enormous numbers of actinobacteria associated with marine organisms. For example,
      RDP classification of these sequences showed that 112 and 62 actinobacterial
      genera were associated with the sponges and corals, respectively. In most cases,
      it is expected that these actinobacteria protect the host against pathogens by
      producing bioactive compounds. Natural products investigation and functional gene
      screening of the actinobacteria associated with the marine organisms revealed
      that they can synthesize numerous natural products including polyketides,
      isoprenoids, phenazines, peptides, indolocarbazoles, sterols, and others. These
      compounds showed anticancer, antimicrobial, antiparasitic, neurological,
      antioxidant, and anti-HIV activities. Therefore, marine organism-associated
      actinobacteria represent an important resource for marine drugs. It is an
      upcoming field of research to search for novel actinobacteria and pharmaceutical
      natural products from actinobacteria associated with the marine organisms. In
      this review, we attempt to summarize the present knowledge on the diversity and
      natural products production of actinobacteria associated with the marine
      organisms, based on the publications from 1991 to 2013.

PMID- 25064353
TI  - Depth-related coupling relation between methane-oxidizing bacteria (MOBs) and
      sulfate-reducing bacteria (SRBs) in a marine sediment core from the Dongsha
      region, the South China Sea.
AB  - The vertical distributions of methane-oxidizing bacteria (MOBs) and sulfate
      reducing bacteria (SRBs) in the marine sediment core of DH-CL14 from the Dongsha
      region, the South China Sea, were investigated. To enumerate MOBs and SRBs, their
      specific genes of pmoA and apsA were quantified by a culture-independent
      molecular biological technique, real-time polymerase chain reaction (RT-PCR). The
      result shows that the pmoA gene copies per gram of sediments reached the maximum
      of 1,118,679 at the depth of 140-160 cm. Overall considering the detection
      precision, sample amount, measurement cost, and sensitivity to the seepage of
      methane from the oil/gas reservoirs or gas hydrates, we suggest that the depth of
      140-160 cm may be the optimal sampling position for the marine microbial
      exploration of oils, gases, and gas hydrates in the Dongsha region. The data of
      the pmoA and apsA gene copies exhibit an evident coupling relation between MOBs
      and SRBs as illustrated in their vertical distributions in this sediment core,
      which may well be interpreted by a high sulfate concentration inhibiting methane
      production and further leading to the reduction of MOBs. In comparison with the
      numbers of the pmoA and apsA copies at the same sediment depth, we find out that
      there were two methane-oxidizing mechanisms of aerobic and anaerobic oxidation in
      this sediment core, i.e., the aerobic oxidation with free oxygen dominantly
      occurred above the depth of 210-230 cm, while the anaerobic oxidation with the
      other electron acceptors such as sulfates and manganese-iron oxides happened
      below the depth of 210-230 cm.

PMID- 25064354
TI  - Tobacco exposure results in increased E6 and E7 oncogene expression, DNA damage
      and mutation rates in cells maintaining episomal human papillomavirus 16 genomes.
AB  - High-risk human papillomavirus (HR-HPV) infections are necessary but insufficient
      agents of cervical and other epithelial cancers. Epidemiological studies support
      a causal, but ill-defined, relationship between tobacco smoking and cervical
      malignancies. In this study, we used mainstream tobacco smoke condensate (MSTS-C)
      treatments of cervical cell lines that maintain either episomal or integrated
      HPV16 or HPV31 genomes to model tobacco smoke exposure to the cervical epithelium
      of the smoker. MSTS-C exposure caused a dose-dependent increase in viral genome
      replication and correspondingly higher early gene transcription in cells with
      episomal HPV genomes. However, MSTS-C exposure in cells with integrated HR-HPV
      genomes had no effect on genome copy number or early gene transcription. In cells
      with episomal HPV genomes, the MSTS-C-induced increases in E6 oncogene
      transcription led to decreased p53 protein levels and activity. As expected from
      loss of p53 activity in tobacco-exposed cells, DNA strand breaks were
      significantly higher but apoptosis was minimal compared with cells containing
      integrated viral genomes. Furthermore, DNA mutation frequencies were higher in
      surviving cells with HPV episomes. These findings provide increased understanding
      of tobacco smoke exposure risk in HPV infection and indicate tobacco smoking acts
      more directly to alter HR-HPV oncogene expression in cells that maintain episomal
      viral genomes. This suggests a more prominent role for tobacco smoke in earlier
      stages of HPV-related cancer progression. 

PMID- 25064355
TI  - A mouse model of KIF5B-RET fusion-dependent lung tumorigenesis.
AB  - Oncogenic fusion of the RET (rearranged during transfection) gene was recently
      identified as a novel driver gene aberration not only for the development of
      thyroid carcinoma but also of lung adenocarcinoma, the most frequent histological
      type of lung cancer. This study constructed and analyzed transgenic mice
      expressing KIF5B-RET, the predominant form of RET fusion gene specific for lung
      adenocarcinoma, under the control of the SPC (surfactant protein C) gene
      promoter. The mice expressed the KIF5B-RET fusion gene specifically in lung
      alveolar epithelial cells, and developed multiple tumors in the lungs. Treatment
      of the transgenic mice with vandetanib, which is a RET tyrosine kinase inhibitor
      approved by the U.S. Food and Drug Administration for the treatment of thyroid
      carcinoma, for 8 or 20 weeks led to a marked reduction in the number of lung
      tumors (3.3 versus 0 and 6.5 versus 0.2 per tissue section, respectively; P <
      0.01, t-test). The results suggest that the RET fusion functions as a driver for
      the development of lung tumors, whose growth is inhibited by RET tyrosine kinase
      inhibitors. 

PMID- 25064356
TI  - Orphan nuclear receptor Nur77 promotes colorectal cancer invasion and metastasis
      by regulating MMP-9 and E-cadherin.
AB  - Nur77, an orphan member of the nuclear receptor superfamily, has been implicated
      in tumorigenesis. However, its contributions to colorectal cancer (CRC) invasion
      and metastasis are largely under characterized. Here, we present the first
      evidence that the invasion and metastasis of CRC is regulated by Nur77. High
      expression of Nur77 was observed in clinical CRC tissues, and this elevated
      expression was significantly associated with advanced tumor, lymph nodes, distant
      metastasis stage (P = 0.003), lymph node metastasis (P = 0.001) and poor survival
      (P = 0.03). Overexpression of Nur77 in CRC cells enhanced cell invasion in vitro,
      whereas knockdown of Nur77 diminished cell invasion and metastasis both in vitro
      and in vivo. In studying the possible mechanism by which overexpression of Nur77
      contributes to CRC invasion and metastasis, we observed that the nuclear protein
      Nur77 promoted the expression of matrix metalloproteinase (MMP)-9, a novel
      downstream target of Nur77, and subsequently decreased the expression of E
      cadherin. Examination of clinical samples further showed that Nur77 expression is
      positively correlated with MMP-9, whereas negatively correlated with E-cadherin.
      Interestingly, Nur77-mediated CRC invasion via MMP-9 and E-cadherin could be
      mimicked by some metastasis-inducible factors including hypoxia and prostaglandin
      E2. Collectively, our study demonstrated that Nur77 could promote the invasion
      and metastasis of CRC cells through regulation of MMP-9/E-cadherin signaling.
      These observations provide a possible new strategy for potentially treating or
      preventing the metastasis of CRC through targeting of Nur77. 

PMID- 25064357
TI  - Impact of cell lines included in enterovirus isolation protocol on perception of
      nonpolio enterovirus species C diversity.
AB  - There has been under-reporting of nonpolio enterovirus species Cs (NPESCs) in
      Nigeria despite the fact that most isolates recovered from the Nigerian vaccine
      derived poliovirus serotype 2 (VDPV2) outbreak were recombinants with
      nonstructural region of NPESC origin. It has been suggested that cell lines
      included in enterovirus isolation protocols might account for this phenomenon and
      this study examined this suggestion. Fifteen environmental samples concentrated
      previously and analysed using L20B and RD cell lines as part of the poliovirus
      environmental surveillance (ES) program in Nigeria were randomly selected and
      inoculated into two cell lines (MCF-7 and LLC-MK2). Isolates were identified as
      enteroviruses and species C members using different RT-PCR assays, culture in
      L20B cell line and sequencing of partial VP1. Forty-eight (48) isolates were
      recovered from the 15 samples, 47 (97.9%) of which were enteroviruses. Of the
      enteroviruses, 32 (68.1%) belonged to enterovirus species C (EC) of which 19
      (40.4%) were polioviruses and 13 (27.7%) were NPESC members. All 13 NPESC
      isolates were recovered on MCF-7. Results of the study show that NPESCs are
      circulating in Nigeria and their under-reporting was due to the combination of
      cell lines used for enterovirus isolation in previous reports. 

PMID- 25064358
TI  - Quantitative PCR assays reveal high prevalence of lymphocryptovirus as well as
      lytic phase gene expression in peripheral blood cells of cynomolgus macaques.
AB  - Lymphocryptoviruses such as Epstein-Barr virus (EBV) are important pathogens in
      both human and non-human primates, particularly during immunosuppression.
      Immunomodulatory molecules that may suppress antiviral immunity are commonly
      tested in the cynomolgus macaque. To enable the study of lymphocryptovirus (LCV)
      in this non-clinical model, PCR-based assays were developed to measure LCV viral
      load, as well as transcripts for the lytic phase LCV gene, BALF-2. Results from
      studies employing these assays showed that LCV genome was detected in the
      oropharyngeal epithelium of all cynomolgus monkeys tested, and the majority had
      viral genome in peripheral blood mononuclear cells (PBMCs). The results also
      revealed LCV lytic phase gene expression not only in the oropharynx of most
      monkeys, but also in PBMCs of approximately one half of monkeys tested. This
      unexpected finding suggests that initiation of the lytic gene expression cascade
      occurs often in the peripheral blood cells of healthy monkeys. 

PMID- 25064359
TI  - Droplet digital PCR as a useful tool for the quantitative detection of
      Enterovirus 71.
AB  - Hand, foot and mouth disease (HFMD) is a contagious viral disease that frequently
      affects infants and children and present with blisters and flu-like symptoms.
      This disease is caused by a group of enteroviruses such as enterovirus 71 (EV71)
      and coxsackievirus A16 (CA16). However, unlike other HFMD causing enteroviruses,
      EV71 have also been shown to be associated with more severe clinical
      manifestation such as aseptic meningitis, brainstem and cerebellar encephalitis
      which may lead to cardiopulmonary failure and death. Clinically, HFMD caused by
      EV71 is indistinguishable from other HFMD causing enteroviruses such as CA16.
      Molecular diagnosis methods such as the use of real-time PCR has been used
      commonly for the identification of EV71. In this study, two platforms namely the
      real-time PCR and the droplet digital PCR were compared for the detection
      quantitation of known EV71 viral copy number. The results reveal accurate and
      consistent results between the two platforms. In summary, the droplet digital PCR
      was demonstrated to be a promising technology for the identification and
      quantitation of EV71 viral copy number. 

PMID- 25064360
TI  - Supported inhibitor for fishing lipases in complex biological media and mass
      spectrometry identification.
AB  - A synthetic phosphonate inhibitor designed for lipase inhibition but displaying a
      broader range of activity was covalently immobilized on a solid support to
      generate a function-directed tool targeting serine hydrolases. To achieve this
      goal, straightforward and reliable analytical techniques were developed, allowing
      the monitoring of the solid support's chemical functionalization, enzyme capture
      processes and physisorption artifacts. This grafted inhibitor was tested on pure
      lipases and serine proteases from various origins, and assayed for the selective
      capture of lipases from several complex biological extracts. The direct
      identification of captured enzymes by mass spectrometry brought the proof of
      concept on the efficiency of this supported covalent inhibitor. The features and
      limitations of this "enzyme-fishing" proteomic tool provide new insight on solid
      liquid inhibition process. 

PMID- 25064361
TI  - Rmcystatin3, a cysteine protease inhibitor from Rhipicephalus microplus hemocytes
      involved in immune response.
AB  - The Rhipicephalus microplus tick is responsible for losses in the livestock
      production estimated in 2 billions USD. Despite its economical importance the
      knowledge in tick's physiology is sparse. In order to contribute to this scenario
      we describe the characterization of a cysteine proteinase inhibitor named
      Rmcystatin-3. Purified recombinant Rmcystatin-3 was able to inhibit cathepsin L
      (Ki = 2.5 nM), BmCl1 (Ki = 1.8 nM) and cathepsin B (Ki = 136 nM). Western blot
      and quantitative PCR analysis revealed the presence of Rmcystatin-3 in fat body,
      salivary gland but mainly in hemocytes. The mRNA levels of Rmcystatin-3 during
      bacterial challenge are drastically down-regulated. In order to define the
      Rmcystatin-3 possible role in tick immunity, the cystatin gene was knockdown by
      RNA interference with and without Escherichia coli infection. Our results showed
      that the Rmcystatin-3 silenced group was more immune competent to control
      bacterial infection than the group injected with non-related dsRNA. Taking
      together, our data strongly suggested an important role of Rmcystatin-3 in tick
      immunity.

PMID- 25064362
TI  - Preconditioning in laparoscopic surgery--results of a virtual reality pilot
      study.
AB  - BACKGROUND: This prospective study investigated the effect of preconditioning in
      laparoscopic cholecystectomy (LC) and appendectomy (LA) based on pre- and
      postoperative virtual reality laparoscopy (VRL) performances, with specific
      regard to the impact of different motor skills, types of surgery and levels of
      experience. STUDY DESIGN: Forty laparoscopic procedures (28 LC and 12 LA) were
      performed by 13 residents in the operating room. Participants completed a defined
      set of tasks on the VRL simulator directly prior to and after the operation: one
      preparational task (PT), a virtual procedural task with emphasis on fine
      preparation (VPT) and a navigational manoeuvre for instrument coordination (ICT).
      VRL performances were evaluated based on the assessed items of the simulator.
      RESULTS: Overall analysis of the surgeons' performance demonstrated better
      postoperative results for PT and VPT in 28 and 26 cases (p = 0.001 and p =
      0.034), respectively. No significant difference was found for ICT (p = 0.638).
      Less-experienced residents had better postoperative results for PT and VPT (p =
      0.009 and p = 0.041), whereas more-experienced surgeons had better postoperative
      results for PT only (p = 0.030). LC resulted in better postoperative performance
      for PT (p = 0.007). LA improved performance for PT and VPT (p = 0.034 and p =
      0.006, respectively). Comparisons of surgeon's experience demonstrated a
      significant advantage for more-experienced surgeons in ICT (p = 0.033), while
      type of surgery showed an advantage for LA in VPT (p = 0.022). CONCLUSION: There
      is a preconditioning effect in laparoscopic surgery. The differing results
      related to LC and LA and the experience levels of surgeons suggest that
      differentiated warm-up strategies are required.

PMID- 25064363
TI  - Bipolar vessel sealing: instrument contamination and wear have little effect on
      seal quality and success in a porcine in vitro model.
AB  - PURPOSE: The aim of this study is to systematically investigate under
      standardized experimental conditions the effects of instrument contamination and
      wear on the quality of bipolar vessel sealing (BVS) achieved using a reusable
      instrument. METHODS: The study was designed as a prospective, randomized, and
      controlled in vitro study and conducted in an academic research environment.
      Reusable bipolar coagulation forceps (BiClamp(r) 200 C, ERBE Elektromedizin) were
      used to apply sealing pressures of 300-1,100 mN/mm(2) to 239 renal arteries from
      commercially slaughtered female pigs (Swabian-Hall Swine). Forceps jaws were
      coated with porcine blood, blood and collagen, or blood, collagen, and fat to
      simulate instrument contamination with biological material during surgery.
      Clinical wear was mimicked by sandpaper abrasion. The main outcome measures were
      seal success (resistance to 250 mmHg intraluminal pressure for 2 min) and seal
      stability (burst pressure). RESULTS: Sealing pressure had a significant impact,
      with 800 mN/mm(2) producing the best sealing results. Seal success increased with
      total energy applied to the tissue, a higher maximum temperature, and longer
      coagulation as indicated by desiccation time. Experimental contamination had no
      significant impact on seal success and only a limited effect on seal stability.
      Similarly, abrasive wear also had no significant effect on either seal quality or
      seal strength. CONCLUSIONS: The impact of bipolar forceps contamination and wear
      on seal success and quality was negligible in our in vitro model. To achieve high
      quality seals, it is essential to use adequate sealing pressures. Our findings
      could have direct implications for the design and clinical handling of BVS
      instruments.

PMID- 25064364
TI  - Effect of gentle stroking and vocalization on behaviour, mucosal immunity and
      upper respiratory disease in anxious shelter cats.
AB  - Emotional, behavioural, and health benefits of gentle stroking and vocalizations,
      otherwise known as gentling, have been documented for several species, but little
      is known about the effect of gentling on cats in stressful situations. In this
      study, 139 cats rated as anxious upon admission to an animal shelter were
      allocated to either a Gentled or Control group. Cats were gentled four times
      daily for 10 min over a period of 10 days, with the aid of a tool for cats that
      were too aggressive to handle. The cats' mood, or persistent emotional state, was
      rated daily for 10 d as Anxious, Frustrated or Content. Gentled cats were less
      likely to have negatively valenced moods (Anxious or Frustrated) than Control
      cats (Incidence Rate Ratio [IRR]=0.61 CI 0.42-0.88, P=0.007). Total secretory
      immunoglobulin A (S-IgA) was quantified from faeces by enzyme-linked
      immunosorbent assay. Gentled cats had increased S-IgA (6.9 +/- 0.7 logeMUg/g)
      compared to Control cats (5.9 +/- 0.5 logeMUg/g) (P<0.0001). Within the Gentled
      group of cats, S-IgA values were higher for cats that responded positively to
      gentling (7.03 +/- 0.6, logeMUg/g), compared with those that responded negatively
      (6.14 +/- 0.8, logeMUg/g). Combined conjunctival and oropharyngeal swab specimens
      were tested by quantitative real-time polymerase chain reaction (rPCR) for feline
      herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Mycoplasma felis,
      Chlamydophila felis, and Bordetella bronchiseptica. There was a significant
      increase in shedding over time in Control cats (23%, 35%, 52% on days 1, 4 and
      10, respectively), but not in gentled cats (32%, 26%, 30% on days 1, 4 and 10,
      respectively) (P=0.001). Onset of upper respiratory disease was determined by
      veterinary staff based on clinical signs, in particular ocular and/or nasal
      discharge. Control cats were 2.4 (CI: 1.35-4.15) times more likely to develop
      upper respiratory disease over time than gentled cats (P<0.0001). It is concluded
      that gentling anxious cats in animal shelters can induce positive affect
      (contentment), increase production of S-IgA, and reduce the incidence of upper
      respiratory disease.

PMID- 25064365
TI  - The risk factors for avian influenza on poultry farms: a meta-analysis.
AB  - BACKGROUND: Avian influenza is a severe threat both to humans and poultry, but so
      far, no systematic review on the identification and evaluation of the risk
      factors of avian influenza infection has been published. The objective of this
      meta-analysis is to provide evidence for decision-making and further research on
      AI prevention through identifying the risk factors associated with AI infection
      on poultry farms. METHODS: The results from 15 selected studies on risk factors
      for AI infections on poultry farms were analyzed quantitatively by meta-analysis.
      RESULTS: Open water source (OR=2.89), infections on nearby farms (OR=4.54), other
      livestock (OR=1.90) and disinfection of farm (OR=0.54) have significant
      association with AI infection on poultry farms. The subgroup analysis results
      indicate that there exist different risk factors for AI infections in different
      types of farms. CONCLUSIONS: The main risk factors for AI infection in poultry
      farms are environmental conditions (open water source, infections on nearby
      farms), keeping other livestock on the same farm and no disinfection of the farm.

PMID- 25064366
TI  - Schmallenberg virus: lessons learned.

PMID- 25064367
TI  - Protein-protein interactions between proteins of Citrus tristeza virus isolates.
AB  - Citrus tristeza virus (CTV) is one of the most devastating pathogens of citrus.
      Its genome is organized into 12 open reading frames (ORFs), of which ten ORFs
      located at the 3'-terminus of the genome have multiple biological functions. The
      ten genes at the 3'-terminus of the genome of a severe isolate (CTV-S4) and three
      ORFs (CP, CPm and p20) of three other isolates (N4, S45 and HB1) were cloned into
      pGBKT7 and pGADT7 yeast shuttle vectors. Yeast two-hybridization (Y2H) assays
      results revealed a strong self-interaction for CP and p20, and a unique
      interaction between the CPm of CTV-S4 (severe) and CP of CTV-N4 (mild) isolates.
      Bimolecular fluorescence complementation also confirmed these interactions.
      Analysis of the deletion mutants delineated the domains of CP and p20 self
      interaction. Furthermore, the domains responsible for CP and p20 self
      interactions were mapped at the CP amino acids sites 41-84 and p20 amino acids
      sites 1-21 by Y2H. This study provided new information on CTV protein
      interactions which will help for further understanding the biological functions.

PMID- 25064369
TI  - Disseminated histoplasmosis in a renal transplant patient.

PMID- 25064368
TI  - The changing incidence of dengue haemorrhagic fever in Indonesia: a 45-year
      registry-based analysis.
AB  - BACKGROUND: Increases in human population size, dengue vector-density and human
      mobility cause rapid spread of dengue virus in Indonesia. We investigated the
      changes in dengue haemorrhagic fever (DHF) incidence in Indonesia over a 45-year
      period and determined age-specific trends in annual DHF incidence. METHODS: Using
      an on-going nationwide dengue surveillance program starting in 1968, we evaluated
      all DHF cases and related deaths longitudinally up to 2013. Population
      demographics were used to calculate annual incidence and case fatality ratios
      (CFRs). Age-specific data on DHF available from 1993 onwards were used to assess
      trends in DHF age-distribution. Time-dependency of DHF incidence and CFRs was
      assessed using the Cochrane-Armitage trend test. RESULTS: The annual DHF
      incidence increased from 0.05/100,000 in 1968 to ~ 35-40/100,000 in 2013, with
      superimposed epidemics demonstrating a similar increasing trend with the highest
      epidemic occurring in 2010 (85.70/100,000; p < 0.01). The CFR declined from 41%
      in 1968 to 0.73% in 2013 (p < 0.01). Mean age of DHF cases increased during the
      observation period. Highest incidence of DHF was observed among children aged 5
      to 14 years up to 1998, but declined thereafter (p < 0.01). In those aged 15
      years or over, DHF incidence increased (p < 0.01) and surpassed that of 5 to 14
      year olds from 1999 onwards. CONCLUSIONS: Incidence of DHF over the past 45 years
      in Indonesia increased rapidly with peak incidence shifting from young children
      to older age groups. The shifting age pattern should have consequences for
      targeted surveillance and prevention.

PMID- 25064370
TI  - A prognostic algorithm including a modified version of MD Anderson Cancer Center
      (MDACC) score predicts time to first treatment of patients with clinical
      monoclonal lymphocytosis (cMBL)/Rai stage 0 chronic lymphocytic leukemia (CLL).
AB  - We propose an algorithm based on a slightly modified version of MD Anderson
      Cancer Center (MDACC) score (i.e., mutational status of IgVH, LDH, presence of
      high-risk FISH abnormalities), beta2-microglobulin and separation of clinical
      monoclonal B-cell lymphocytosis (cMBL) from chronic lymphocytic leukemia (CLL) to
      predict time to first treatment (TTFT) of a prospective multicentre cohort
      including 83 cMBL and 136 CLL Rai stage 0 patients. Patients with MDACC score
      point >=38, at any level of beta2-microglobulin and irrespective of whether they
      fulfilled 2008 International Workshop on CLL (IWCLL) criteria for CLL Rai stage 0
      or cMBL, experienced the worst clinical outcome (5-year TTFT, 24%) and formed the
      high-risk group. In contrast, subjects with a diagnosis of cMBL, MDACC score
      point <38 and beta2-microglobulin <= UNL had the best clinical outcome (5-year
      TTFT, 100%) and constituted the low-risk group. The intermediate group included
      patients in Rai stage 0, MDACC score point <38, and any level of beta2
      microglobulin, and patients with cMBL, MDACC score point <38, and beta2
      microglobulin >= UNL. Cases showing these features can be grouped together to
      form the intermediate-risk group (5-year TTFT, 65%). Although the separation
      between cMBL and Rai stage 0, as proposed by the 2008 IWCLL guidelines, has
      clinical implications, the model we propose may help to classify patients with
      cMBL and Rai stage 0 into more precise subgroups suggesting that a prognostic
      separation of these entities based solely on clonal B-cell threshold may be
      unsatisfactory.

PMID- 25064371
TI  - Factor X M402T: a homozygous missense mutation identified as the cause of cross
      reacting material-reduced deficiency.
AB  - We investigated a mildly hemorrhagic patient with factor X (FX) deficiency to
      identify the nature of his defect by comprehensive analyses. A 42-year-old
      Japanese man was admitted to our hospital for uncontrolled gingival hemorrhage.
      His FX activity based on prothrombin time (PT) and activated partial
      thromboplastin time (aPTT) and FX antigen were <1, 6.5 and 11 %, respectively. A
      homozygous M402T missense mutation (c.1205 t>c; p.Met402Thr) was identified in
      the FX gene (F10) from both the patient and his brother. The mutation was not
      detected in the F10 of 82 unrelated normal Japanese individuals. We studied the
      functional consequences of this mutation by expressing mutant FX-M402T protein in
      HEK293 cells. This analysis revealed that the antigen of the FX-M402T mutants was
      approximately 26 % that of the wild-type FX in conditioned media. The FX-specific
      activity of FX-M402T mutants measured by a one-stage clotting assay based upon PT
      and aPTT, and a chromogenic assay using Russell's viper venom in the concentrated
      media was 7.7, 31.7, and 41.2 % of wild type, respectively. The results suggest
      that the mutation FX-M402T may cause a secretion defect and a molecular
      abnormality in FX. 

PMID- 25064372
TI  - Patient and public attitudes to and awareness of clinical practice guidelines: a
      systematic review with thematic and narrative syntheses.
AB  - BACKGROUND: Clinical practice guidelines are typically written for healthcare
      providers but there is increasing interest in producing versions for the public,
      patients and carers. The main objective of this review is to identify and
      synthesise evidence of the public's attitudes towards clinical practice
      guidelines and evidence-based recommendations written for providers or the
      public, together with their awareness of guidelines. METHODS: We included
      quantitative and qualitative studies of any design reporting on public, patient
      (and their carers) attitudes and awareness of guidelines written for providers or
      patients/public. We searched electronic databases including MEDLINE, PSYCHINFO,
      ERIC, ASSIA and the Cochrane Library from 2000 to 2012. We also searched relevant
      websites, reviewed citations and contacted experts in the field. At least two
      authors independently screened, abstracted data and assessed the quality of
      studies. We conducted a thematic analysis of first and second order themes and
      performed a separate narrative synthesis of patient and public awareness of
      guidelines. RESULTS: We reviewed 5415 records and included 26 studies (10
      qualitative studies, 13 cross sectional and 3 randomised controlled trials)
      involving 24 887 individuals. Studies were mostly good to fair quality. The
      thematic analysis resulted in four overarching themes: Applicability of
      guidelines; Purpose of guidelines for patient; Purpose of guidelines for health
      care system and physician; and Properties of guidelines. Overall, participants
      had mixed attitudes towards guidelines; some participants found them empowering
      but many saw them as a way of rationing care. Patients were also concerned that
      the information may not apply to their own health care situations. Awareness of
      guidelines ranged from 0-79%, with greater awareness in participants surveyed on
      national guideline websites. CONCLUSION: There are many factors, not only
      formatting, that may affect the uptake and use of guideline-derived material by
      the public. Producers need to make clear how the information is relevant to the
      reader and how it can be used to make healthcare improvements although there were
      problems with data quality. Awareness of guidelines is generally low and
      guideline producers cannot assume that the public has a more positive perception
      of their material than of alternative sources of health information.

PMID- 25064373
TI  - Mendelian randomization: genetic anchors for causal inference in epidemiological
      studies.
AB  - Observational epidemiological studies are prone to confounding, reverse causation
      and various biases and have generated findings that have proved to be unreliable
      indicators of the causal effects of modifiable exposures on disease outcomes.
      Mendelian randomization (MR) is a method that utilizes genetic variants that are
      robustly associated with such modifiable exposures to generate more reliable
      evidence regarding which interventions should produce health benefits. The
      approach is being widely applied, and various ways to strengthen inference given
      the known potential limitations of MR are now available. Developments of MR,
      including two-sample MR, bidirectional MR, network MR, two-step MR, factorial MR
      and multiphenotype MR, are outlined in this review. The integration of genetic
      information into population-based epidemiological studies presents translational
      opportunities, which capitalize on the investment in genomic discovery research. 

PMID- 25064374
TI  - Irinophore CTM, a lipid nanoparticle formulation of irinotecan, abrogates the
      gastrointestinal effects of irinotecan in a rat model of clinical toxicities.
AB  - Irinotecan is a water-soluble camptothecin derivative with clinical activity
      against colorectal and small cell lung cancers and is currently a standard of
      care therapeutic in the treatment of colorectal cancer in combination with 5
      fluorouracil. One of the major clinical issues limiting the use of irinotecan is
      gastrointestinal toxicity manifested as life-threatening diarrhea which is
      reported in up to 45% of treated patients. The studies summarized here tested, in
      a rat model of irinotecan-associated gastro-intestinal toxicity, whether a lipid
      nanoparticle formulation of irinotecan, Irinophore CTM, mitigated early-onset or
      late-onset diarrhea when given at doses equivalent to unformulated irinotecan
      that engenders both early- and late-onset diarrhea. Specifically, rats
      administered intravenously on two consecutive days with unformulated irinotecan
      at 170 mg/kg then 160 mg/kg experienced transient early-onset diarrhea after each
      administration and then experienced significant late-onset diarrhea peaking 4
      days after treatment. Irinophore CTM given at the identical dose and schedule did
      not elicit either early- or late-onset diarrhea in any animals. When Irinophore
      CTM was combined with 5-fluorouracil there was also no early- or late-onset
      diarrhea observed. Histopathological analysis of the gastro-intestinal tract
      confirmed that the effects associated with irinotecan treatment were absent in
      rats given Irinophore CTM at the identical dose. Pharmacokinetic analysis
      demonstrated significantly higher systemic concentrations of irinotecan in rats
      given the nanoparticle formulation compared to those given unformulated
      irinotecan. These results demonstrate that the Irinophore CTM formulation is
      significantly less toxic than irinotecan, used either as a single agent or in
      combination with 5-fluorouracil, in a rat model of irinotecan-induced
      gastrointestinal toxicity.

PMID- 25064375
TI  - Emissions of amides (N,N-dimethylformamide and formamide) and other obnoxious
      volatile organic compounds from different mattress textile products.
AB  - The emission rates of N,N-dimethylformamide (DMF), formamide (FAd), and certain
      hazardous volatile organic compounds (VOCs) were measured from seventeen mattress
      textile samples with four different raw material types: polyurethane (PU: n=3),
      polyester/polyethylene (PE: n=7), ethylene vinyl acetate (EV: n=3), and polyvinyl
      chloride (PC: n=4). To simulate the emissions in a heated room during winter
      season, measurements were made under temperature-controlled conditions, i.e., 50
      degrees C by using a mini-chamber system made of a midget impinger. Comparison of
      the data indicates that the patterns were greatly distinguished between DMF and
      FAd. PU products yielded the highest mean emission rates of DMF (2940 MUg m(-2)h(
      1): n=3) followed by PE (325 MUg m(-2)h(-1): n=7), although its emission was not
      seen from other materials (EV and PC). In contrast, the pattern of FAd emission
      was moderately reversed from that of DMF: EV>PC>PE>PU. The results of our
      analysis confirm that most materials used for mattress production have the strong
      potential to emit either DMF or FAd in relatively large quantities while in use
      in children's care facilities, especially in winter months. Moreover, it was also
      observed that an increase in temperature (25 degrees C to 50 degrees C) had a
      significant impact on the emission rate of FAd and other hazardous VOCs. In
      addition to the aforementioned amides, the study revealed significant emissions
      of a number of hazardous VOCs, such as aromatic and carbonyl compounds.

PMID- 25064376
TI  - Relatively high motivation for context-evoked reward produces the magnitude
      effect in rats.
AB  - Using a concurrent-chain schedule, we demonstrated the effect of absolute
      reinforcement (i.e., the magnitude effect) on choice behavior in rats. In
      general, animals' simultaneous choices conform to a relative reinforcement ratio
      between alternatives. However, studies in pigeons and rats have found that on a
      concurrent-chain schedule, the overall reinforcement ratio, or absolute amount,
      also influences choice. The effect of reinforcement amount has also been studied
      in inter-temporal choice situations, and this effect has been referred to as the
      magnitude effect. The magnitude effect has been observed in humans under various
      conditions, but little research has assessed it in animals (e.g., pigeons and
      rats). The present study confirmed the effect of reinforcement amount in rats
      during simultaneous and inter-temporal choice situations. We used a concurrent
      chain procedure to examine the cause of the magnitude effect during inter
      temporal choice. Our results suggest that rats can use differences in
      reinforcement amount as a contextual cue during choice, and the direction of the
      magnitude effect in rats might be similar to humans when using the present
      procedure. Furthermore, our results indicate that the magnitude effect was caused
      by the initial-link effect when the reinforcement amount was relatively small,
      while a loss aversion tendency was observed when the reinforcement amount changed
      within a session. The emergence of the initial-link effect and loss aversion
      suggests that rats make choices through cognitive processes predicted by prospect
      theory. 

PMID- 25064377
TI  - Can the difference in serum concentration of urea and cystatin C be used in
      diagnosis and prognosis of heart failure?
AB  - Changes in renal function are an important diagnostic and prognostic indicator in
      patients with heart failure (HF). They are caused by decreased renal perfusion
      and consequently decreased glomerular filtration rate (GFR), or by the effect of
      increased neurohormonal activity (sympathetic nervous system [SNS], rennin
      angiotensin-aldosterone system [RAAS] and arginine vasopressin [AVP]). However,
      the increase of serum concentration of urea, creatinine and other metabolites is
      not specific for HF. Therefore, it is not possible to distinguish HF from renal
      diseases solely based on the increase of their concentration, since the increase
      of their concentration caused by the decrease of GFR cannot be differentiated
      from the increase due to neurohormonal activity. Urea and cystatin C (Cys C) have
      different mechanisms of renal elimination, so it can be assumed that in HF their
      concentrations will not be increased proportionally, what can be used for
      diagnostic and prognostic purposes. After glomerular filtration Cy C undergoes
      proximal tubular reabsorption and breakdown, without returning to the blood flow.
      Since it is not secreted, its serum concentration depends only on GFR. In
      contrast to Cys C, urea is filtered in glomerulus and subsequently reabsorbed in
      proximal tubules and collecting duct. Reabsorption of urea is modified by effects
      of SNS, RAAS and AVP. Therefore its serum concentration depends upon GFR and
      neurohormonal effect on the tubular function. Since the increase of serum
      concentration of Cys C is caused only by the effect of the decreased renal
      perfusion on GFR, while the increase of urea is a result from both decreased GFR
      and tubular effects of increased neurohormonal activity, the paper hypothesis is
      that in HF the increase of urea will be significantly higher than the increase of
      serum Cys C, while in the patients with renal diseases their increase would be
      mostly proportional. It can be assumed that the disproportion between the
      increase of Cys C and urea would indicate an increased neurohormonal activity in
      patients with HF and correlate with its activity. If this hypothesis is proved
      correct, this parameter could be used in HF diagnosis and risk stratification of
      such patients.

PMID- 25064378
TI  - Reclassification of clinical sleep disorders using traditional models of
      syndromic, neuroanatomic, pathophysiological and etiological diagnosis.
AB  - Existing classifications of central nervous system sleep disorders do not often
      provide tools to diagnose the majority of patients complaining of sleep-related
      symptoms, nor always guide effective treatment. I present a novel classification
      system that completely separates clinical syndromes from anatomical localization,
      pathophysiology, and etiology. The clinical syndrome I present can describe the
      majority of patients, but can be fractionated into individual subgroups for
      further study. By then separating the anatomy and physiology from the symptoms,
      an avenue of research becomes available to study the different possible
      structures that regulate sleep, that may be damaged and cause syndromes of sleep
      dysfunction. Some of these may produce symptoms that overlap with narcolepsy and
      some may be distinct. Because the clinical syndrome should be distinguished from
      anatomy or physiology, I have proposed the term narcoleptiform syndrome for the
      clinical syndrome. The model also clearly separates etiology from anatomy in a
      classical neurological manner. This allows etiology, localization and symptoms to
      be studied separately. It is likely that different etiologies may produce damage
      in areas that produce similar syndromes. For example, in this model, different
      causes of damage to the orexin nucleus would result in the same clinical
      syndrome. This reinforces the concept of studying anatomy, symptoms and etiology
      separately. By studying the relationship of syndromes or symptoms to anatomic
      localization and pathophysiology, it should be possible to test novel approaches
      to treatment based on different underlying structure or function. For example,
      patients with lesions in the ventrolateral preoptic nucleus or the thalamic
      intralaminar nuclei may both present with insomnia symptoms but need different
      treatment; or they might present with symptoms overlapping narcolepsy (a
      narcoleptiform syndrome) yet need different treatment. In some cases, a single
      treatment may cross over more than one location, and the best predictor might be
      symptoms. These are issues that need to undergo careful study on a syndromic,
      anatomic and physiological bases. This novel model opens up new avenues for
      understanding central nervous system sleep disorders, providing testable
      hypotheses regarding diagnosis and treatment. 

PMID- 25064379
TI  - Melatonin as potential inducer of Th17 cell differentiation.
AB  - The subset of T lymphocytes producing IL-17 (Th17) plays a key role in the immune
      system. It has been implicated in host defense, inflammatory diseases,
      tumorigenesis, autoimmune diseases, and transplant rejection. Careful analysis of
      the data available holds that Th17 cell subpopulation should be under the direct
      control of pineal hormone melatonin: the key Th17 differentiation factor RORalpha
      serves in the meantime as a high-affinity melatonin receptor. Since the levels of
      melatonin have diurnal and seasonal variation, as well as substantial deviations
      in some physiological or pathological conditions, melatonin-dependent regulation
      of Th17 cells should implicate multiform manifestation, such as influencing the
      outcome of infectious challenge or determining predisposition, etiology and
      progression of immune-related morbidities. Another important reason to raise a
      point of the new melatonin effects is current considering the possibilities of
      its clinical trials. Especially, the differentiation of Th17 upon melatonin
      treatment must aggravate the current recession in autoimmune diseases or induce
      serious complications in pregnancy.

PMID- 25064380
TI  - Changes in oxidized low-density lipoprotein cholesterol are associated with
      changes in handgrip strength in Japanese community-dwelling persons.
AB  - Nordic walking (NW), characterized by the use of two walking poles, has positive
      effects on several muscle groups. Muscle strength and mass decrease with age, and
      recently, this decrease is defined as sarcopenia. Sarcopenia may be triggered by
      oxidative stress. We investigated whether changes in the oxidative stress marker,
      malondialdehyde-modified low-density lipoprotein (MDA-LDL)/LDL-cholesterol (LDL
      C) ratio are associated with change in handgrip strength (HGS), which is a useful
      indicator of sarcopenia, by a 12-week NW exercise among Japanese community
      dwelling persons. The present study included 65 women aged 67+/-7 years and 9 men
      aged 71+/-8 years from a rural village. NW exercise of 120 min per week was
      performed for 12 weeks. Before and at the end of the 12-week intervention,
      various confounding factors and HGS were measured. 12-week changes in various
      factors were calculated by subtracting the baseline values from the 12-week
      values. Changes in HGS and follow-up HGS increased progressively with decreased
      changes in the MDA-LDL/LDL-C ratio after the 12-week walking exercise (r=-0.32,
      P=0.006 and r=-0.35, P=0.002, respectively). Multiple linear regression analysis
      showed that changes in HDL-C (beta=0.26, P=0.019) and MDA-LDL/LDL-C ratio (beta=
      0.32, P=0.004) were significantly and independently associated with changes in
      HGS. When the data were further stratified by gender, change in the MDA-LDL/LDL-C
      ratio was significantly and similarly associated with change in HGS in women
      only. These results suggest that change in MDA-LDL/LDL-C ratio may be a predictor
      for HGS after a 12-week NW exercise in community-dwelling persons.

PMID- 25064381
TI  - The prevalence of thyroid autoimmunity in patients with urticaria: a systematic
      review and meta-analysis.
AB  - Thyroid autoimmunity is the most common organ-specific autoimmune disorder, which
      is characterized by the production of thyroid autoantibodies and lymphocytic
      infiltration into the thyroid. The majority cases of chronic urticaria have
      unknown (idiopathic) causes, with about 30-40 % possibly having an autoimmune
      substrate. Considering that autoimmune factors may be the common features of both
      thyroid autoimmunity and urticaria, it is likely that both entities may coexist
      within the same patient. A number of studies have investigated the association
      between thyroid autoimmunity and urticaria. However, most of these studies are
      relatively small sample size, the power achieved in those studies was not
      sufficient to detect whether there is an association between urticaria and
      thyroid autoimmunity. The aim of this study is to combine primary data from all
      relevant studies to produce reliable estimates of the associations between
      thyroid autoantibodies and urticaria. Literature databases were searched
      including Medline, Embase, Web of Science, Chinese Wanfang, and CBM databases
      from January 1980 to December 2013. A total of 14,203 urticaria cases and 12,339
      non-urticaria controls were included in this study. From these data, the odds
      ratio (OR) with 95% confidence interval (95% CI) was calculated. The meta
      analysis results showed that the prevalence of positive thyroid autoantibodies in
      patients with urticaria was higher than non-urticaria controls (TgAb: OR 6.55,
      95% CI 3.19-13.42, P<0.00001, I2=67%; TmAb: OR 4.51, 95% CI 2.78-7.33, P<0.00001,
      I2=47%; TPOAb: OR 8.71, 95% CI 6.89-11.01, P<0.00001, I2=20%, respectively). The
      results of this meta-analysis suggested that patients with urticaria were more
      likely to have thyroid autoimmunity than the control groups.

PMID- 25064382
TI  - Alteration of thyroid hormone levels and related gene expression in Chinese rare
      minnow larvae exposed to mercury chloride.
AB  - Mercury is a prominent environmental contaminant that causes endocrine disorder
      to human and other organisms. But little is known about the response of the
      thyroid functions and hypothalamic-pituitary-thyroid (HPT) axis to mercury in
      teleosts and the few studies that are available have not yielded consistent
      results. In this study, expression profiles of corticotropin-releasing hormone
      (crh), thyroid stimulating hormone beta (tshbeta), solute carrier family 5
      (sodium iodide symporter) member 5 (slc5a5), thyroglobulin (tg), thyroid hormone
      receptor alpha (tralpha) and thyroid hormone receptor beta (trbeta) genes were
      determined in whole-body of Chinese rare minnow (Gobiocypris rarus) larvae after
      exposure to different levels of Hg(2+) (0, 0.1 and 0.3 mg/l) for 4 days, as well
      as the thyroid hormones (THs) levels. Moreover, the 96-h lethal concentration of
      Hg(2+) on rare minnow larvae was determined as 0.32 mg/l. The results showed that
      crh, tg, tralpha and trbeta mRNA levels were significantly up-regulated in the
      larvae, but the gene expression of tshbeta and slc5a5 was not significantly
      changed in our study. Besides, the THs levels increased in the whole-body of
      fish, especially the thyroxine (T4) level. The above results indicated that
      Hg(2+) could alter some genes expression in the HPT axis which could be used as
      the potential biomarkers for evaluating the environmental Hg(2+)-induced stress
      in fish.

PMID- 25064383
TI  - Blood manganese levels in relation to comorbid behavioral and emotional problems
      in children with attention-deficit/hyperactivity disorder.
AB  - Patients with attention-deficit/hyperactivity disorder (ADHD) appear to be more
      vulnerable to the development of other psychiatric disorders than the general
      population. The proposed neurotoxic mechanisms of manganese involve striatal
      dopamine neurotransmission, implicated in the pathophysiology of ADHD. We
      investigated whether the adverse impact of manganese is particularly pronounced
      in children with ADHD. Blood manganese concentration and diagnosis of ADHD were
      assessed in a general population of 890 children, aged 8-11 years. The main
      outcome measure was the Child Behavior Checklist (CBCL). A significant
      interaction was found between ADHD status and blood manganese level in predicting
      CBCL total problems score as well as anxiety/depression, social problems,
      delinquent behavior, aggressive behavior, internalizing problems, and
      externalizing problems. The directions of the interactions indicated that blood
      manganese level was more positively correlated with CBCL scores in ADHD children
      than in the healthy population. In ADHD children, only the fifth quintile of
      blood manganese concentration was significantly associated with the CBCL total
      problems score. ADHD children may be more vulnerable than the general school-age
      population to the neurotoxic effects of manganese exposure, which lead to an
      elevated risk of developing comorbid mental conditions. 

PMID- 25064384
TI  - Intermittent Explosive Disorder and aversive parental care.
AB  - Parental bonding has been shown to have lasting impacts on the psychological
      development of children. Despite a growing body of research examining trauma as
      it relates to Intermittent Explosive Disorder (IED), no prior research has
      examined the relationship between parental bonding and IED. Six hundred fifty
      eight subjects were studied and categorized into one of three groups: Normal
      Control (no history of current or lifetime Axis I or Axis II disorder),
      Psychiatric Control (current and/or lifetime Axis I and/or Axis II disorders
      without IED), and IED (met current and/or lifetime criteria for IED). Self
      reported parental care was assessed using the Parental Bonding Inventory (PBI).
      PBI Care scores were lowest among IED subjects, which were lower than among
      Psychiatric Control subjects, which were lower than among Normal Control
      subjects. PBI Control scores were highest among IED and Psychiatric Control
      subjects, which were higher than among Normal Control subjects. The diagnostic
      group differences in PBI Care/PBI Control scores were not impacted by the number
      of Axis I/II diagnoses. The findings in this study expand the link between
      childhood trauma exposure, violent behavior, and IED. This is the first report of
      an association of IED with an aversive childhood parenting environment. 

PMID- 25064385
TI  - Association between GUC2C and ADHD: evidence from both categorical and
      quantitative traits.
AB  - Guanylyl cyclase-C knock-out mice exhibit hyperactivity and attention deficits.
      We investigated seven single nucleotide polymorphisms (SNPs) of Guanylate cyclase
      2C gene (GUC2C) in 381 ADHD trios and 382 healthy controls. Transmission
      disequilibrium tests (TDT), case-control studies and quantitative analyses
      indicated association between GUC2C with ADHD and its core symptoms. 

PMID- 25064386
TI  - Material-specific discrepancies in verbal and visual episodic memory in
      borderline personality disorder.
AB  - Material-specific discrepancies in episodic memory were evaluated in 24 patients
      with borderline personality disorder. Compared to norms, large discrepancies
      between verbal and visual episodic memory, measured using the Hopkins Verbal
      Learning Test and Brief Visuospatial Memory Test, respectively, were
      significantly more frequent among patients, occurring three times more often than
      in the normative sample. Although visual memory was hypothesized to be more
      significantly affected, patients showed no consistent decrement to verbal or
      visual memory. 

PMID- 25064387
TI  - Public perceptions of stigma towards people with schizophrenia, depression, and
      anxiety.
AB  - Stigma is one of the greatest challenges facing people with a psychiatric
      diagnosis. They are widely stigmatised by the general public in the western
      world. The aim of this study was to examine public stigma attitudes towards
      schizophrenia, depression and anxiety. The Office of National Statistics (ONS)
      2008 opinions survey (n=1070) was utilised. Percentage of endorsements for stigma
      items were initially compared to the previous 1998 and 2003 databases. Overall
      stigma attitudes had decreased (from 1998 to 2008) but increased since 2003. A
      principal components factor analysis identified that stigma attitudes have the
      same three factors structure across all diagnoses; negative stereotypes, patient
      blame and inability to recover. Schizophrenia was significantly associated with
      the most negative stereotypes, least blamed and viewed as least likely to recover
      compared to anxiety and depression. Public and individualised interventions that
      target diagnostic variability in stigma attitudes need to be developed and
      examined in future research. 

PMID- 25064388
TI  - Subjective and physiological emotional response in euthymic bipolar patients: a
      pilot study.
AB  - The euthymic phase of bipolar disorders may be associated with residual emotional
      and/or subsyndromal symptoms. The aim of this study was to compare subjective and
      physiologic emotional response to negative, neutral and positive emotion
      eliciting pictures between euthymic bipolar patients (n=26) and healthy controls
      (n=30). We evaluated emotional response using an emotional induction method with
      emotional pictures from the International Affective Picture System. We measured
      subjective emotional response with the Self-Assessment Manikin and physiological
      emotional response by measuring pupil size. No difference was found between
      euthymic bipolar patients and controls regarding subjective emotional response.
      However, upon viewing positive pictures, pupil dilation was significantly lower
      in euthymic bipolar patients compared to controls. This finding suggests that
      euthymic bipolar phase may be associated with reduced physiologic emotional
      response to positive valence, which is consistent with a more general negative
      emotional bias or can be understood as a residual emotional subsyndromal symptom.

PMID- 25064389
TI  - Perineal wound healing after abdominoperineal resection for rectal cancer: a two
      centre experience in the era of intensified oncological treatment.
AB  - PURPOSE: Intensified treatment for distal rectal cancer has improved oncological
      outcome, but at the expense of more perineal wound complications in patients
      undergoing an abdominoperineal resection (APR). The aim of this study was to
      analyse perineal wound healing after APR with primary perineal wound closure over
      time. METHOD: All patients undergoing APR for primary rectal cancer with primary
      wound closure between 2000 and 2013 were included and analysed in three
      consecutive time periods. Both early (<30 days postoperatively) and late perineal
      wound complications were determined. Independent risk factors of early perineal
      wound complications were identified using multivariable analysis. RESULTS: A
      total of 136 patients were identified, of whom 129 patients underwent primary
      perineal wound closure. The use of neo-adjuvant (chemo)radiotherapy increased
      from 72 to 91%, and the use of an extralevator approach increased from 9 to 19%.
      The rate of early perineal wound complications increased from 18 to 31% and was
      independently associated with an extralevator approach [odds ratio (OR) 3.17; 95%
      confidence interval (CI) 1.16-8.66] and intra-operative perforation (OR 3.35; 95%
      CI 1.06-10.57). Perineal wound complications had no impact on local recurrence or
      3-year overall survival rate. During a median follow-up of 28 months
      [interquartile range (IQR) 14-56], a persistent presacral sinus was diagnosed in
      10%, and a perineal hernia occurred in 8% of the patients. CONCLUSION: The
      increased use of an extralevator APR for rectal cancer significantly increased
      the risk of perineal wound complications over time. Intra-operative perforation
      was also independently associated with impaired perineal wound healing.

PMID- 25064390
TI  - Evaluation of four comorbidity indices and Charlson comorbidity index adjustment
      for colorectal cancer patients.
AB  - INTRODUCTION: Cancer survival is related not only to primary malignancy but also
      to concomitant nonmalignant diseases. The aim of this study was to investigate
      the prognostic capacity of four comorbidity indices [the Charlson comorbidity
      index (CCI), the Elixhauser method, the National Institute on Aging (NIA) and
      National Cancer Institute (NCI) comorbidity index, and the Adult Comorbidity
      Evaluation-27 (ACE-27)] for both cancer-related and all-cause mortality among
      colorectal cancer patients. A modified version of the CCI adapted for colorectal
      cancer patients was also built. METHODS: The study population comprised 468 cases
      of colorectal cancer diagnosed between 1 January 2000 and 31 December 2010 at a
      community hospital. Data were prospectively collected and abstracted from
      patients' clinical records. Kaplan-Meier method and multivariate logistic
      regression models were performed for survival and risk of death analysis.
      RESULTS: Only moderate or severe renal disease [hazard ratio (HR) 2.71, 95%
      confidence interval (CI) 1.11-6.63] and AIDS (HR 3.27, 95% CI 1.23-8.68) were
      independently associated with cancer-specific mortality, with a population
      attributable risk of 5.18 and 4.36%, respectively. For each index, the highest
      comorbidity burden was significantly associated with poorer overall survival
      (NIA/NCI: HR 2.14, 95% CI 1.14-4.01; Elixhauser: HR 1.98, 95% CI 1.09-1.42; ACE
      27: HR 1.78, 95% CI 1.07-1.23; CCI: HR 1.68, 95% CI 1.05-1.42) and cancer
      specific survival. The modified version of the CCI resulted in a higher
      predictive power compared with other indices studied (cancer-specific mortality
      HR = 2.37, 95% CI 1.37-4.08). CONCLUSIONS: The comorbidity assessment tools
      provided better prognostic prevision of prospective outcome of colorectal cancer
      patients than single comorbid conditions.

PMID- 25064391
TI  - Prognostic value of treatment-related factors in metastatic colorectal cancer
      using a stop-and-go strategy.
AB  - PURPOSE: The purpose of this study is to identify treatment-related factors
      prognostic of survival in a cohort of patients with metastatic colorectal cancer
      (mCRC) receiving a palliative, stop-and-go chemotherapy regimen. METHODS:
      Consecutive patients receiving first-line treatment with biweekly FLIRI plus
      bevacizumab were included. The outcome was overall survival. Cox regression
      analysis was used to identify predictors of outcome. We analysed reduction in
      chemotherapy dosage (no vs. <=25 or >25 % reduction), bevacizumab administrated
      to <50, or >=50 % to chemotherapy treatments, best response during the first 24
      weeks of treatment, and local treatment of metastases. RESULTS: We included 257
      patients. Median survival was 23.6 months. Chemotherapy reduction did not
      influence outcome. Bevacizumab administrations (>=50 %) were associated with
      improved outcome: hazard ratios (HR) 0.56 (95 % confidence interval (CI) 0.34
      0.90, p = 0.018). Partial response (PR) vs. no change (NC) was borderline
      significant: HR 0.66 (95 % CI 0.43-0.99, p = 0.048), whereas progressive disease
      (PD) vs. NC increased mortality HR 2.48 (95 % CI 1.19-5.19, p = 0.016). Local
      treatment of metastases improved outcome: HR 0.30 (95 % CI 0.15-0.61, p = 0.001).
      CONCLUSIONS: In a cohort of mCRC patients, receiving a palliative, stop-and-go
      regimen, administration of bevacizumab to >=50 % of chemotherapy treatments and
      local treatment of metastases were associated with better survival. PR improved
      outcome compared to NC, whereas PD was prognostic of increased mortality.

PMID- 25064392
TI  - Changing patterns of septic tenosynovitis of the distal extremities.
AB  - The medical literature reports that human pyogenic tenosynovitis occurs almost
      exclusively in flexor tendons of distal extremities with only rare case reports
      in extensor compartments. We report a series of patients with septic extensor
      compartment tenosynovitis of the extremity. Twenty cases of septic tenosynovitis
      tendons of the wrist, hands, feet, and ankles were presented to our emergency
      department over a 4.17-year period, 15 men (one, twice over a 2.5-year span) and
      4 women with an average age of 39 years. Diagnosis was made using CT (n = 6), MRI
      (n = 14), and in one case ultrasound (US). All cases were confirmed surgically.
      During the data collection period, no case of flexor septic tenosynovitis were
      presented. All patients were intravenous drug users. All imaging modalities
      showed fluid within the infected tendon sheaths and evidence of enhancement after
      contrast administration where contrast was administered. The single US showed
      hypervascularity on Doppler imaging. All wrist and hand infections (n = 15)
      occurred in the non-dominant hand, and all cases involved the fourth and next
      most commonly (n = 9 each) in the second and third extensor compartments. In the
      ankle and foot (n = 5), the extensor digitorum longus tendon was most commonly
      infected. Twelve patients (60 %) had soft tissue abscesses adjacent to infected
      tendon sheaths. The most common organism cultured from the tendon sheaths was
      Staphylococcus aureus, methicillin sensitive and resistant and often admixed with
      other flora. Common use of intravenous drugs now makes extensor septic
      tenosynovitis an important clinical diagnosis and likely now more common than
      flexor septic tenosynovitis.

PMID- 25064393
TI  - Valley-dependent spin polarization in bulk MoS2 with broken inversion symmetry.
AB  - The valley degree of freedom of electrons is attracting growing interest as a
      carrier of information in various materials, including graphene, diamond and
      monolayer transition-metal dichalcogenides. The monolayer transition-metal
      dichalcogenides are semiconducting and are unique due to the coupling between the
      spin and valley degrees of freedom originating from the relativistic spin-orbit
      interaction. Here, we report the direct observation of valley-dependent out-of
      plane spin polarization in an archetypal transition-metal dichalcogenide--MoS2-
      using spin- and angle-resolved photoemission spectroscopy. The result is in fair
      agreement with a first-principles theoretical prediction. This was made possible
      by choosing a 3R polytype crystal, which has a non-centrosymmetric structure,
      rather than the conventional centrosymmetric 2H form. We also confirm robust
      valley polarization in the 3R form by means of circularly polarized
      photoluminescence spectroscopy. Non-centrosymmetric transition-metal
      dichalcogenide crystals may provide a firm basis for the development of magnetic
      and electric manipulation of spin/valley degrees of freedom.

PMID- 25064394
TI  - Electronic modulation of biochemical signal generation.
AB  - Microelectronic devices that contain biological components are typically used to
      interrogate biology rather than control biological function. Patterned assemblies
      of proteins and cells have, however, been used for in vitro metabolic
      engineering, where coordinated biochemical pathways allow cell metabolism to be
      characterized and potentially controlled on a chip. Such devices form part of
      technologies that attempt to recreate animal and human physiological functions on
      a chip and could be used to revolutionize drug development. These ambitious goals
      will, however, require new biofabrication methodologies that help connect
      microelectronics and biological systems and yield new approaches to device
      assembly and communication. Here, we report the electrically mediated assembly,
      interrogation and control of a multi-domain fusion protein that produces a
      bacterial signalling molecule. The biological system can be electrically tuned
      using a natural redox molecule, and its biochemical response is shown to provide
      the signalling cues to drive bacterial population behaviour. We show that the
      biochemical output of the system correlates with the electrical input charge,
      which suggests that electrical inputs could be used to control complex on-chip
      biological processes. 

PMID- 25064395
TI  - Metabolic engineering: enzyme control on a chip.

PMID- 25064396
TI  - Interconnected hollow carbon nanospheres for stable lithium metal anodes.
AB  - For future applications in portable electronics, electric vehicles and grid
      storage, batteries with higher energy storage density than existing lithium ion
      batteries need to be developed. Recent efforts in this direction have focused on
      high-capacity electrode materials such as lithium metal, silicon and tin as
      anodes, and sulphur and oxygen as cathodes. Lithium metal would be the optimal
      choice as an anode material, because it has the highest specific capacity (3,860
      mAh g(-1)) and the lowest anode potential of all. However, the lithium anode
      forms dendritic and mossy metal deposits, leading to serious safety concerns and
      low Coulombic efficiency during charge/discharge cycles. Although advanced
      characterization techniques have helped shed light on the lithium growth process,
      effective strategies to improve lithium metal anode cycling remain elusive. Here,
      we show that coating the lithium metal anode with a monolayer of interconnected
      amorphous hollow carbon nanospheres helps isolate the lithium metal depositions
      and facilitates the formation of a stable solid electrolyte interphase. We show
      that lithium dendrites do not form up to a practical current density of 1 mA cm(
      2). The Coulombic efficiency improves to ~ 99% for more than 150 cycles. This is
      significantly better than the bare unmodified samples, which usually show rapid
      Coulombic efficiency decay in fewer than 100 cycles. Our results indicate that
      nanoscale interfacial engineering could be a promising strategy to tackle the
      intrinsic problems of lithium metal anodes.

PMID- 25064397
TI  - Batteries: a stable lithium metal interface.

PMID- 25064398
TI  - Integrative DNA methylation and gene expression analysis identifies discoidin
      domain receptor 1 association with idiopathic nonobstructive azoospermia.
AB  - OBJECTIVE: To evaluate the association between promoter DNA methylation and
      discoidin domain receptor 1 (DDR1) gene expression in men with nonobstructive
      azoospermia (NOA). DESIGN: Comparing fibroblasts cultured from testicular
      biopsies using a high resolution Infinium 450K methylation array. SETTING: Basic
      research laboratory. PATIENT(S): Men with NOA (n = 16) and with normal
      spermatogenesis (n = 5). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Bisulfite clonal sequencing for validation and quantification of CpG methylation
      of DDR1; gene expression analysis of DDR1 with quantitative polymerase chain
      reaction and immunohistochemistry to validate the array results at mRNA and
      protein levels. RESULT(S): We validated promoter methylation, mRNA and protein
      levels of the CpG sites identified from array results. Differentially methylated
      CpG sites (~20K) were identified using an F-test in the NOA samples. We
      identified 20 genes with >30% difference in DNA methylation within the promoter
      region of men with NOA and fertile controls. Of the aberrantly methylated genes,
      10 were hypomethylated and 10 were hypermethylated genes. From the top 10
      hypermethylated genes, six genes (MRI1, DCAF12L1, TMEM95, CECR2, DDR1, and NPHS2)
      were selected for validation because they were shown to be expressed in the
      testis. Of the six genes expressed in the fibroblasts cultured from testis, DDR1
      showed an abnormal gene expression pattern. Three patients (19%) out of the 16
      men with NOA for whom gene expression data were available had lower DDR1
      expression levels (1.8x fold decrease) than the fertile men, whereas four (25%)
      men had higher expression levels (2x fold increase) of DDR1 compared with the
      levels in fertile men. Quantitative analysis by bisulfite clonal sequencing
      showed that one of the CpG sites (cg13329862) of DDR1 promoter was
      hypermethylated in NOA patients compared with fertile controls (53% vs. 15%).
      Immunohistochemical analysis suggests presence of DDR1 within cytoplasm of germ
      cells and peritubular connective tissue (in men with hypospermatogenesis) and
      decreased expression of the protein in men with Sertoli-cell only syndrome.
      CONCLUSION(S): Abnormal gene expression of DDR1 is associated with NOA. The
      functional relevance of aberrant methylation of DDR1 to expression of DDR1 in men
      with NOA warrants further investigation.

PMID- 25064399
TI  - Repetitive oocyte donation: a committee opinion.
AB  - This Committee Opinion concludes that donors be advised of the number of
      cycles/donations that a given oocyte donor may undergo. Although existing data
      cannot permit conclusive recommendations, a concern for the issues of the safety
      and well-being of oocyte donors warrants consideration. This document replaces
      the document of the same name, previously published in 2008 (Fertil Steril 2008;
      90:S194-5). 

PMID- 25064400
TI  - Recommended practices for the management of embryology, andrology, and
      endocrinology laboratories: a committee opinion.
AB  - This document provides a general overview for physicians of the qualities and
      conditions necessary for good management practices within the endocrinology,
      andrology, and embryology laboratories in the United States. It is intended as an
      addendum to previously published guidelines that further detail these
      responsibilities. 

PMID- 25064401
TI  - Effect of oocyte vitrification on deoxyribonucleic acid methylation of H19, Peg3,
      and Snrpn differentially methylated regions in mouse blastocysts.
AB  - OBJECTIVE: To examine whether mouse oocytes vitrification could alter the
      deoxyribonucleic acid (DNA) methylation of differentially methylated regions
      (DMRs) of three imprinted genes in in vitro fertilized blastocysts. DESIGN: In
      vitro experiments using murine model. SETTING: State key laboratory and
      university research laboratory. ANIMAL(S): Kunming white mice. INTERVENTION(S):
      The mouse metaphase II oocytes were vitrified. After thawing, the surviving
      oocytes were fertilized in vitro to produce blastocysts. The blastocysts derived
      in vitro from fresh oocytes were used as a control. The DNA methylation patterns
      of the DMRs of imprinted genes in oocytes and blastocysts and the relative
      expression of DNMTs (Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3l) in oocytes and
      blastocysts were detected. MAIN OUTCOME MEASURE(S): Methylation patterns of DMRs
      of H19, Peg3, and Snrpn analyzed by bisulfite mutagenesis and sequencing.
      Expression levels of messenger ribonucleic acid as measured by real-time reverse
      transcriptase polymerase chain reaction. RESULT(S): After oocytes vitrification,
      the methylation levels at H19, Peg3, and Snrpn DMRs in blastocysts were
      decreased. However, there was no significant difference in the percentage of
      hypermethylated strands at Peg3 DMRs between the vitrified and control groups.
      DNMTs expression in vitrified oocytes and the expression of Dnmt3b in blastocysts
      derived from vitrified oocytes were significantly reduced. CONCLUSION(S): Oocytes
      vitrification could lead to the loss of DNA methylation of imprinted genes (H19,
      Peg3, and Snrpn) in mouse blastocysts, which is mainly caused by the reductions
      of DNMTs after vitrification of oocytes.

PMID- 25064402
TI  - Genome-wide copy number analysis and systematic mutation screening in 58 patients
      with hypogonadotropic hypogonadism.
AB  - OBJECTIVE: To clarify the molecular basis of hypogonadotropic hypogonadism (HH).
      DESIGN: Genome-wide copy number analysis by array-based comparative genomic
      hybridization and systematic mutation screening of 29 known causative genes by
      next-generation sequencing, followed by in silico functional assessment and
      messenger RNA/DNA analyses of the mutants/variants. SETTING: Research institute.
      PATIENT(S): Fifty-eight patients with isolated HH (IHH), combined pituitary
      hormone deficiency (CPHD), and syndromic HH. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Frequency and character of molecular abnormalities. RESULT(S):
      Pathogenic defects were identified in 14 patients with various types of HH,
      although oligogenicity was not evident in this patient group. As rare
      abnormalities, we identified a submicroscopic deletion involving FGFR1 and an
      SOX3 polyalanine deletion in patients with IHH, and a WDR11 splice site mutation
      in a patient with CPHD. No disease-associated polymorphism was detected in the 58
      patients. CONCLUSION(S): The present study provides further evidence that
      mutations and deletions in the known causative genes play a relatively minor role
      in the etiology of HH and that submicroscopic rearrangements encompassing FGFR1
      can lead to IHH as a sole recognizable clinical feature. Furthermore, the results
      indicate for the first time that polyalanine deletions in SOX3 and mutations in
      WDR11 constitute rare genetic causes of IHH and CPHD, respectively.

PMID- 25064403
TI  - Gene-gene interactions and risk of recurrent miscarriages in carriers of
      endocrine gland-derived vascular endothelial growth factor and prokineticin
      receptor polymorphisms.
AB  - OBJECTIVE: To study endocrine gland-derived vascular endothelial growth factor
      (EG-VEGF), prokineticin receptor (PROKR) 1, and PROKR2 variants in the coding
      regions of idiopathic recurrent miscarriage (RM) patients and further evaluate
      gene-gene interactions of these three genes. DESIGN: Case-control study. SETTING:
      University-based reproductive clinics and genetics laboratory. PATIENT(S): A
      total of 142 women with a history of idiopathic RM and 149 control subjects were
      included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): All blood samples were
      nucleotide sequenced in the coding regions of EG-VEGF, PROKR1, and PROKR2. Gene
      gene interaction of three gene variants was evaluated with the use of the
      multifactor dimensionality reduction method. RESULT(S): One nonsynonymous variant
      of each of the three genes was identified, and PROKR1 (I379V) and PROKR2 (V331M)
      were significantly associated with idiopathic RM. Genetic interactions were found
      not only between PROKR1 (I379V) and PROKR2 (V331M), but also among EG-VEGF
      (V67I), PROKR1 (I379V), and PROKR2 (V331M). Women carrying low-risk genotypes had
      a 77% reduced risk of experiencing miscarriages compared with those carrying high
      risk genotypes. CONCLUSION(S): The present study corroborates the clinical
      relevance of the EG-VEGF system in human early pregnancy, and provides evidence
      for the gene-gene interactions of EG-VEGF and PROKR variants.

PMID- 25064404
TI  - Assessment of the implantation of day-2 human embryos by morphometric
      nonsubjective parameters.
AB  - OBJECTIVE: To demonstrate the usefulness of image analysis in designing objective
      embryonic morphometric variables. DESIGN: Retrospective study of 214 top-quality
      day-2 embryo photographs from 50 double-embryo transfers resulting in no
      pregnancy (group 0) and 57 resulting in twin pregnancy (group 1). SETTING: Human
      reproduction unit. PATIENT(S): Study of 107 in vitro fertilization
      intracytoplasmic sperm injection (IVF-ICSI) cycles in women age <36 years with
      double-embryo transfer of top-quality embryos. Only the first cycle of IVF-ICSI
      was included. INTERVENTION(S): Standard IVF-ICSI protocols. MAIN OUTCOME
      MEASURE(S): The embryo photographs were analyzed using the ImageJ program. The
      effects of the embryo variables and the clinical variables on embryo implantation
      were evaluated using a stepwise dichotomous logistic regression. RESULT(S):
      Significant differences were observed, owing to the women's ages, internal
      perimeter, roundness factor, and zona pellucida thickness. Embryos with smaller
      internal perimeter, circular shape, and thinner zona pellucida were more likely
      to implant. CONCLUSION(S): Morphometric variables lower the subjectivity of the
      current embryo grading systems. These variables are nonsubjective factors to
      consider when predicting implantation. Embryo image analysis is an accurate tool
      that can improve IVF-ICSI outcomes and reduce the number of twin pregnancies.

PMID- 25064405
TI  - Image-guided drainage versus antibiotic-only treatment of pelvic abscesses: short
      term and long-term outcomes.
AB  - OBJECTIVE: To determine the efficacy of image-guided drainage versus antibiotic
      only treatment of pelvic abscesses. DESIGN: Retrospective cohort analysis.
      SETTING: An academic, inner-city medical center. PATIENT(S): Women ages 11-49,
      admitted between 1998 and 2008 with ICD9 code 614.x (inflammatory diseases of
      ovary, fallopian tube, pelvic cellular tissue, and peritoneum). INTERVENTION(S):
      Medical records search, chart review, and phone survey. MAIN OUTCOME MEASURE(S):
      Surgical intervention. RESULT(S): We identified 6,151 initial patients, of whom
      240 patients met inclusion criteria. Of the included patients, 199 women received
      antibiotic-only treatment, and 41 received additional image-guided drainage.
      There was no statistically significant difference between the two groups in terms
      of age, body mass index, parity, incidence of diabetes, obesity, endometriosis,
      or history of sexually transmitted infection excluding human immunodeficiency
      virus (HIV). Abscesses in the drainage cohort were noted to be larger in
      dimension (5.9 cm vs. 8.5 cm); 16.1% of patients who received antibiotics alone
      required surgical intervention versus only 2.4% of the drainage cohort. Patients
      who received drainage had longer hospital stays, but the time from treatment to
      discharge was similar in both groups (7.4 days vs. 6.7 days). We successfully
      contacted 150 patients, and the differences in long-term pregnancy outcomes,
      pain, or infertility were not statistically significant. CONCLUSION(S): Patients
      who received antibiotics alone were more likely to require further surgical
      intervention when compared with patients who additionally received image-guided
      drainage. There were no observable long-term differences.

PMID- 25064406
TI  - Association of abdominal obesity, insulin resistance, and oxidative stress in
      adipose tissue in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To study the expression of insulin signaling-related genes and
      oxidative stress markers in the visceral adipose tissue obtained from polycystic
      ovary syndrome (PCOS) patients and healthy control subjects and to investigate
      the relationships among abdominal obesity, insulin resistance, and oxidative
      stress at the tissue level. DESIGN: Case-control study. SETTING: University
      teaching hospital. PATIENT(S): In total, 30 PCOS patients and 30 healthy control
      subjects, who underwent laparoscopic surgery, were included in the study.
      INTERVENTION(S): Abdominal obesity was defined based on waist circumference (WC).
      The homeostasis model index was used to assess insulin resistance (HOMA-IR). MAIN
      OUTCOME MEASURE(S): Gene expression of glucose transporter 4 (GLUT4) and insulin
      receptor substrate 1 (IRS1) in visceral adipose tissue (VAT) and the parameters
      of oxidative stress, such as superoxide dismutase, enzyme glutathione reductase,
      and dimethylarginine, were measured, and the expression of protein oxidative
      damage product 3-nitro-tyrosine residues (nitrotyrosine) in VAT was identified
      with the use of immunohistochemistry. RESULT(S): PCOS was associated with lower
      expression of GLUT4 and IRS1 and a higher level of oxidative stress in VAT, which
      was strongly correlated with WC and HOMA-IR. Presence of abdominal obesity
      further intensified the correlations observed in our measurements. The
      nitrotyrosine expression in VAT was stronger in PCOS patients. CONCLUSION(S): The
      strong correlation of insulin resistance with oxidative stress at the VAT level
      suggests that local oxidative stress and abnormalities of insulin signaling in
      adipose tissue play critical roles in the pathogenesis of PCOS.

PMID- 25064407
TI  - Incidence of hypertension, stroke, coronary heart disease, and diabetes in women
      who have delivered after in vitro fertilization: a population-based cohort study
      from Sweden.
AB  - OBJECTIVE: To compare the incidence of hypertension, stroke, coronary heart
      disease, and diabetes in women who have delivered after in vitro fertilization
      (IVF) with those who delivered after natural conception. DESIGN: A cohort study
      in Sweden between 1990 and 2008. SETTING: Sweden. PATIENT(S): 23,498 women who
      had given birth to a child after IVF and 116,960 individually matched women.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence rates of hypertension,
      diabetes, stroke, and coronary heart disease in both groups. RESULT(S): Inpatient
      and outpatient diagnoses of hypertension, stroke, coronary heart disease, and
      diabetes were identified by linkage to the Swedish National Patient Register. The
      mean time of follow-up was 8.6 years in both groups. Multivariable analysis
      showed that hypertension had a higher incidence in IVF mothers with a hazard
      ratio (HR) of 1.27, 95% confidence interval (CI) 1.13-1.41, as compared with
      mothers from the Medical Birth Register. There was a trend to a higher incidence
      of stroke (HR 1.27; 95% CI, 0.96-1.68), but the incidence of coronary heart
      disease and diabetes did not differ. CONCLUSION(S): Hypertension was more
      prevalent in the IVF group, which suggests that these women should be aware of
      their blood pressure and cardiovascular risk profile.

PMID- 25064408
TI  - Obstetric and perinatal outcome of babies born from vitrified oocytes.
AB  - OBJECTIVE: To assess outcomes after oocyte vitrification on obstetric and
      perinatal outcomes compared with those achieved with fresh oocytes. DESIGN:
      Retrospective cohort study. SETTING: Private university-affiliated IVF center.
      PATIENT(S): Children born after use of vitrified oocytes (1,027 from 804
      pregnancies) and fresh oocytes (1,224 from 996 pregnancies). Singleton and
      multiples pregnancies from own and donated ova were included. INTERVENTION(S):
      Oocyte vitrification by the Cryotop method. MAIN OUTCOME MEASURE(S): Pregnancy,
      delivery, and neonatal outcomes. RESULT(S): Vitrification had no clinically
      relevant adverse effects on obstetric and perinatal outcomes after adjusting for
      potential confounders. No differences were found between the vitrified and fresh
      oocyte groups in the rate of obstetric problems (including diabetes, pregnancy
      induced hypertension, preterm birth, anemia, and cholestasis), gestational age at
      delivery, birth weight, Apgar scores, birth defects, admission to neonatal
      intensive care unit (ICU), perinatal mortality, and puerperal problems. Only a
      greater number of invasive procedures (adjusted odds ratio 2.12; 95% confidence
      interval 1.41-3.20), and a reduced occurrence of urinary tract infection
      (adjusted odds ratio 0.51; 95% confidence interval 0.28-0.91), were observed in
      the vitrified oocytes group. CONCLUSION(S): Although our data, the largest series
      to date, suggest that oocyte vitrification does not increase adverse obstetric
      and perinatal outcomes in children conceived with vitrified oocytes, further
      studies with larger samples are required to reinforce our conclusions.

PMID- 25064409
TI  - Neonatal outcome after preimplantation genetic diagnosis.
AB  - OBJECTIVE: To examine whether embryo biopsy for preimplantation genetic diagnosis
      (PGD) influences neonatal outcomes. DESIGN: Prospective follow-up cohort.
      SETTING: Tertiary university-affiliated medical center. PATIENT(S): 242 children
      born after PGD, 242 children born after intracytoplasmic sperm injection (ICSI)
      (158 singletons and 42 twins pairs in each group), and 733 children born after a
      spontaneous conception (SC) (493 singletons, 120 twins pairs), matched for
      maternal age, parity, and body mass index. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Gestational age, birth weight, prematurity (<37 and <34 weeks), low
      birth weight (<2,500 g, very low birth weight, <1,500 g), and intrauterine growth
      restriction (<10th percentile for gestational age). RESULT(S): For singletons,
      the mean birth weight was higher after SC compared with ICSI but not compared
      with PGD. Mean gestational ages were lower after PGD and ICSI compared with SC.
      The low birth weight and intrauterine growth restriction rates were 4.4%, 12.0%,
      and 5.7% and 5.1%, 9.5%, and 5.5% for PGD, ICSI, and SC, respectively. Similar
      results were found when controlled for the number of embryos transferred and
      cryopreservation. The results for twins exhibited similar but less statistically
      significant trends. Polar body and blastomere biopsies provided similar outcomes.
      CONCLUSION(S): Embryo biopsy itself did not cause intrauterine growth restriction
      or low birth weight compared with SC, despite lower gestational ages with PGD.
      The worsened outcomes in ICSI compared with PGD pregnancies may be due to the
      infertility itself.

PMID- 25064410
TI  - Effect of local endometrial injury on pregnancy outcomes in ovum donation cycles.
AB  - OBJECTIVE: To evaluate the effect of local endometrial injury (LEI) on clinical
      outcomes in ovum donation recipients. DESIGN: Retrospective cohort analysis of
      ovum donation cycles conducted from 2005 to 2012. SETTING: Two private IVF
      centers. PATIENT(S): Total 737 ovum donation cycles. INTERVENTION(S): LEI by
      endometrial "scratch" with the use of a Pipelle catheter. MAIN OUTCOME
      MEASURE(S): Clinical pregnancy and live birth rates. RESULT(S): No statistically
      significant differences were found in clinical pregnancy rates and live birth
      rates in cycles subjected to LEI compared with those without. Combination of LEI
      with fibroid uterus resulted with significantly higher clinical pregnancy rates
      compared with LEI in normal uterine anatomy. CONCLUSION(S): This is the first
      study done in ovum recipients who underwent LEI by a "scratch" procedure after
      failed implantation. Unlike most previous reports, which found improved pregnancy
      rates with the use of "scratch effect" or "minor endometrial injury" after
      repeated implantation failures in standard IVF with own eggs, we did not find any
      changes in implantation rates in a population of egg recipients following this
      procedure. In view of a possible positive effect of LEI in cycles with a previous
      four or more failures, prospective randomized controlled studies are warranted to
      better define the target population who may benefit from this intervention.

PMID- 25064411
TI  - Physical activity is not related to semen quality in young healthy men.
AB  - OBJECTIVE: To study the relationship of physical activity with semen quality
      among healthy young men from Spain. DESIGN: Cross-sectional study. SETTING:
      University and college campuses of Murcia Region, Spain. PATIENT(S): Healthy
      young men with untested fertility (n = 215). INTERVENTION(S): A physical
      examination, blood and semen samples, and completion of a questionnaire. MAIN
      OUTCOME MEASURE(S): Semen quality parameters. RESULT(S): Physical activity was
      not related to semen quality parameters. The adjusted percentage differences (95%
      confidence interval) in semen parameters comparing men in the top quartile of
      moderate-to-vigorous physical activity (>=9.5 h/wk) with men in the bottom
      quartile (<=3 h/wk) were 4.3% (-30.2%, 38.9%) for total sperm count, 7.2% (
      30.6%, 45.1%) for sperm concentration, -2.42% (-6.53%, 1.69%) for sperm motility,
      and 12.6% (-12.0%, 37.2%) for sperm morphology. CONCLUSION(S): In contrast to
      previous research among athletes, these data suggest that physical activity is
      not deleterious to testicular function, as captured by semen quality parameters
      in this population of healthy young men in Spain.

PMID- 25064412
TI  - Perinatal outcomes in 6,338 singletons born after intrauterine insemination in
      Denmark, 2007 to 2012: the influence of ovarian stimulation.
AB  - OBJECTIVE: To study perinatal outcomes in singletons born after intrauterine
      insemination (IUI) compared with children born after in vitro fertilization
      (IVF), intracytoplasmic sperm injection, and spontaneous conception (SC), and to
      assess predictors of poor outcome in singletons born after IUI, exploring the
      effect of ovarian stimulation. DESIGN: National cohort study, 2007-2012. SETTING:
      Danish national registries. PATIENT(S): Four thousand two hundred twenty-eight
      singletons born after insemination with partner semen (IUI-H) and 1,881
      singletons born after insemination with donor semen. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Preterm birth (PTB), low birth weight (LBW), small for
      gestational age (SGA). RESULT(S): Children born after IUI-H had higher risks of
      PTB, LBW, and SGA vs. SC singletons (adjusted odds ratios [aOR] 1.3; 95%
      confidence interval (CI), 1.1-1.5; 1.4; 95% CI, 1.2-1.7; and 1.4; 95% CI, 1.2
      1.6), respectively. Compared with IVF, risk of SGA was similar, but risks of PTB
      and LBW were lower (aOR 0.6; 95% CI, 0.5-0.8; and 0.8; 95% CI, 0.6-0.9). Compared
      with intracytoplasmic sperm injection, no differences were found. For children
      born after IUI with donor semen, results were similar to those for IUI-H. Risks
      of LBW and SGA were higher in IUI singletons born after ovarian stimulation with
      clomiphene citrate, compared with natural-cycle IUI (aOR 1.5; 95% CI, 1.1-2.1 and
      1.6; 95% CI, 1.1-2.4). Treatment with follicle-stimulating hormone vs. natural
      cycle IUI did not seem to affect perinatal outcomes. CONCLUSION(S): Singletons
      born after IUI had higher risk of adverse perinatal outcomes compared with SC
      children, similar to ICSI, but favorable outcomes compared with IVF. Stimulation
      with clomiphene citrate was associated with higher risk of SGA compared with
      natural-cycle IUI, but follicle-stimulating hormone treatment did not seem to be
      associated with adverse outcomes.

PMID- 25064413
TI  - Pigment epithelium-derived factor exerts antioxidative effects in granulosa
      cells.
AB  - OBJECTIVE: To determine whether supplementing granulosa cells cultures with
      pigment epithelium-derived factor (PEDF) can protect them from oxidative stress.
      DESIGN: We used either granulosa cell line or human primary granulosa cell
      culture from women undergoing in vitro fertilization (IVF) treatments. SETTING:
      University research facilities. ANIMAL(S): Imprinting control region female mice.
      INTERVENTION(S): Recombinant PEDF (rPEDF) was added to cultures of either primary
      granulosa cell culture or granulosa cell line in the present or absence of H2O2
      triggering. MAIN OUTCOME MEASURE(S): We followed cell viability with the use of
      methylthiazolyl tetrazolium assay and tracked PEDF mechanism of action with the
      use of Western blot analysis, measuring the level of SOD-1 and GPX-1 mRNA,
      protein level of BAX, and phosphorylation of AKT. RESULT(S): We found that
      granulosa cell viability and the level of PEDF mRNA were both significantly
      reduced, in a dose-dependent manner, after exposure to H2O2. The rate of H2O2
      induced apoptosis was significantly attenuated in granulosa cells treated with
      rPEDF. We showed that granulosa cells, of both humans and rodents, express the
      PEDF receptor, PNPLA2; once stimulated by rPEDF, the cells exhibited
      phosphorylation of AKT. Finally, we showed that PEDF exerts its antioxidative
      activity through the AKT signaling pathway. CONCLUSION(S): This study
      demonstrates that PEDF represents a novel intrinsic antioxidant of granulosa
      cells.

PMID- 25064414
TI  - [The changes in the oxygen saturations in the superior vena cava and the
      pulmonary artery are not the same during cardiac surgery].
AB  - OBJECTIVE: To evaluate the changes over time (trend) in sign and magnitude for
      SSVO2 and SVO2 during and after cardiac surgery. PATIENTS AND METHODS: A
      prospective and observational study was conducted on 34 cardiac surgery patients.
      Venous blood samples were taken simultaneously from the introductor (SVCO2) and
      distal (SVO2) port of the pulmonary artery catheter at predefined intervals.
      Systemic and pulmonary hemodynamic variables were measured at the same time. The
      trend was calculated as the difference between 2 consecutive measurements (tSO2).
      Data were processed with ANOVA for multiple comparisons, Pearson correlation
      coefficient and Bland-Altman analysis. RESULTS: There was a significant
      correlation between SVCO2 and tSVO2 (R(2)=0.55), the mean of the differences was
      0.36+/-7.75%, and the limits of agreement ranged from -15.1 to 15.9%. The sign of
      the trend was similar in 85.1% of the paired data. However, the magnitude of the
      changes in tSVCO2 and tSVO2 were not always equivalent. Between 0 and 5% of the
      change in the tSVCO2 was coincident with only 44.7% of the tSVO2. A wide
      variation was found between both trends when the signs and magnitudes of the
      changes were taken into account. CONCLUSIONS: When considering the sign and
      magnitude, the change over time of central venous O2 saturations were not
      interchangeable in cardiac surgery patients. Clinical decisions based exclusively
      on tSVCO2 monitoring should be taken with caution.

PMID- 25064415
TI  - Gender susceptibility for cigarette smoking-attributable lung cancer: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: As the primary cause of lung cancer, whether smoking confers the same
      risk of lung cancer for women as men is unclear. Therefore, we aimed to compare
      male and female susceptibility for cigarette smoking-attributable lung cancer.
      METHODS: A systematic review and meta-analysis was conducted by searching
      articles published up to July 2013 in three online databases (MEDLINE, EMBASE,
      and Cochrane Database). All studies estimated the association of cigarette
      smoking with the risk of lung cancer between men and women, respectively. A
      random effects model with inverse variance weighting was used to pool data. Male
      to female ratio of relative risk (RRR) was calculated to compare male and female
      susceptibility for cigarette smoking-attributable lung cancer. RESULTS: 47
      articles containing 404,874 individuals were included in the final analysis.
      Compared with non-smokers, male to female RRR was 1.61 (95%CI: 1.37, 1.89) among
      current smokers. Based on pathological type, adenocarcinoma had the highest RRR
      (1.42; 95%CI: 0.86, 2.35), followed by squamous cancer and small cell lung
      cancer. Furthermore, compared with non-smoking men, current smoking men had
      higher risk of lung cancer than women in spite of smoking quantity, smoking
      duration or years since quitting. CONCLUSIONS: These findings indicated that
      males had higher susceptibility for cigarette smoking-attributable lung cancer
      than females. It is contradicted with traditional opinion that females would be
      more easily suffered from cigarette smoking-attributable health problems than
      males. Hence, tobacco control is very crucial in both males and females.

PMID- 25064416
TI  - An acute care surgery dilemma: emergent laparoscopic cholecystectomy in patients
      on aspirin therapy.
AB  - BACKGROUND: The current literature regarding hemorrhagic complications in
      patients on long-term antiplatelet therapy undergoing emergent laparoscopic
      cholecystectomy is limited. The aim of our study was to describe hemorrhagic
      complications in patients on prehospital aspirin (ASP) therapy undergoing
      emergent cholecystectomy. METHODS: We performed a 1-year retrospective analysis
      of our prospectively maintained acute care surgery database. The 2 groups (ASP
      group vs No ASP group) were matched in a 1:1 ratio for age, sex, previous
      abdominal surgeries, and comorbidities. Primary outcome measures were
      intraoperative hemorrhage, postoperative anemia, need for blood transfusion, and
      conversion to open cholecystectomy. Intraoperative hemorrhage was defined as
      intraoperative blood loss of >= 100 mL; postoperative anemia was defined by >= 2
      g/dL drop in hemoglobin. RESULTS: A total of 112 (ASP: 56, no ASP: 56) patients
      were included in the analysis. The mean age was 65.9 +/- 10 years, and 50% were
      male. There was no difference in age (P = .9), sex (P = .9), and comorbidities (P
      = .7) between the 2 groups. There was no difference in intraoperative blood loss
      >100 mL (P = .5), postoperative anemia (P = .8), blood transfusion requirement (P
      = .9), and conversion to open surgery (P = .7) between patients on American
      Society of Anesthesiologists therapy and patients not on American Society of
      Anesthesiologists therapy. CONCLUSIONS: Emergent laparoscopic cholecystectomy is
      a safe procedure in patients on long-term ASP. Prehospital use of ASP as an
      independent factor should not be used to delay emergent cholecystectomy.

PMID- 25064417
TI  - Information/education page. Pseudobulbar affect.

PMID- 25064418
TI  - Altered development and multifaceted band-specific abnormalities of resting state
      networks in autism.
AB  - BACKGROUND: Extensive evidence indicates that cortical connectivity patterns are
      abnormal in autism spectrum disorders (ASD), showing both overconnectivity and
      underconnectivity. Since, however, studies to date have focused on either spatial
      or spectral dimensions, but not both simultaneously, much remains unknown about
      the nature of these abnormalities. In particular, it remains unknown whether
      abnormal connectivity patterns in ASD are driven by specific frequency bands, by
      spatial network properties, or by some combination of these factors. METHODS:
      Magnetoencephalography recordings (15 ASD, 15 control subjects) mapped back onto
      cortical space were used to study resting state networks in ASD with both spatial
      and spectral specificity. The data were quantified using graph theoretic metrics.
      RESULTS: The two major factors that drove the nature of connectivity
      abnormalities in ASD were the mediating frequency band and whether the network
      included frontal nodes. These factors determined whether clustering and
      integration were increased or decreased in cortical resting state networks in
      ASD. These measures also correlated with abnormalities in the developmental
      trajectory of resting state networks in ASD. Lastly, these measures correlated
      with ASD severity in some frequency bands and spatially specific subnetworks.
      CONCLUSIONS: Our findings suggest that network abnormalities in ASD are
      widespread, are more likely in subnetworks that include the frontal lobe, and can
      be opposite in nature depending on the frequency band. These findings thus
      elucidate seemingly contradictory prior findings of both overconnectivity and
      underconnectivity in ASD.

PMID- 25064420
TI  - The impact of obesity on the 30-day morbidity and mortality after surgery for
      endometrial cancer.
AB  - STUDY OBJECTIVES: To examine the effect of body mass index (BMI) on postoperative
      30-day morbidity and mortality after surgery to treat endometrial cancer. DESIGN:
      Retrospective cohort study (Canadian Task Force classification II-2). SETTING:
      National Surgical Quality Improvement Program. PATIENTS: Patients with
      endometrial cancer who underwent surgery from 2005 to 2011. INTERVENTIONS: Women
      were grouped according to weight, as follows: normal weight (BMI 18 to <30),
      obese (BMI 30 to <40), and morbidly obese (BMI >= 40). Univariate and
      multivariable logistic regression models were analyzed. MEASUREMENTS AND MAIN
      RESULTS: Of 3947 patients, 38% were of normal weight, 38% were obese, and 24%
      were morbidly obese. Of these, 48% underwent laparoscopy and 52% underwent
      laparotomy. Overall 30-day morbidity and mortality were 13% and 0.7%,
      respectively. Obesity and morbid obesity were associated with a higher American
      Society of Anesthesiologists class, diabetes, and hypertension. Preoperatively,
      elevated serum creatinine concentration, hypoalbuminemia, and leukocytosis were
      more common in morbidly obese women than those of normal weight. Laparoscopic
      surgery was performed less frequently in morbidly obese women than in those of
      normal weight (42.5% vs 50%; p = .001). Morbidly obese patients were more likely
      to develop postoperative complications (morbidly obese 16% vs normal weight 13%
      vs obese 11%; p = .001), in particular surgical (morbidly obese 14% vs normal
      weight 11% vs obese 9%; p < .001) and infectious complications (morbidly obese
      10% vs normal weight 5% vs obese 5%; p = .01). After laparotomy, morbidly obese
      women demonstrated a higher rate of any complication (normal weight 21%, obese
      18%, morbidly obese 25%; p = .002), surgical complications (normal weight 18%,
      obese 14%, morbidly obese 22%; p = .002) and infectious complications (normal
      weight 6%, obese 10%, morbidly obese 16%; p < .001). After laparoscopy there was
      no difference in complication rates according to BMI group. The 30-day mortality
      was not significantly different according to BMI. After adjusting for
      confounders, obesity and morbid obesity did not independently predict 30-day
      morbidity or mortality. CONCLUSIONS: Morbidly obese patients with endometrial
      cancer have more preoperative morbidities and postoperative complications, in
      particular surgical and infectious complications, and are less likely to undergo
      minimally invasive surgery. However, obesity was not an independent predictor of
      perioperative outcomes after controlling for other confounders.

PMID- 25064419
TI  - The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically
      ascertained population.
AB  - BACKGROUND: Deletion of the recurrent ~600 kb BP4-BP5 chromosomal region 16p11.2
      has been associated with a wide range of neurodevelopmental outcomes. METHODS: To
      clarify the phenotype of 16p11.2 deletion, we examined the psychiatric and
      developmental presentation of predominantly clinically referred individuals, with
      a particular emphasis on broader autism phenotype characteristics in individuals
      with recurrent ~600 kb chromosome 16p11.2 deletions. Using an extensive
      standardized assessment battery across three clinical sites, 85 individuals with
      the 16p11.2 deletion and 153 familial control subjects were evaluated for symptom
      presentation and clinical diagnosis. RESULTS: Individuals with the 16p11.2
      deletion presented with a high frequency of psychiatric and developmental
      disorders (>90%). The most commonly diagnosed conditions were developmental
      coordination disorder, phonologic processing disorder, expressive and receptive
      language disorders (71% of individuals >3 years old with a speech and language
      related disorder), and autism spectrum disorder. Individuals with the 16p11.2
      deletion not meeting diagnostic criteria for autism spectrum disorder had a
      significantly higher prevalence of autism-related characteristics compared with
      the familial noncarrier control group. Individuals with the 16p11.2 deletion had
      a range of intellectual ability, but IQ scores were 26 points lower than
      noncarrier family members on average. CONCLUSIONS: Clinically referred
      individuals with the 16p11.2 deletion have high rates of psychiatric and
      developmental disorders and provide a genetically well-defined group to study the
      emergence of developmental difficulties, particularly associated with the broader
      autism phenotype.

PMID- 25064421
TI  - Is level of exposure to a 12-step facilitation therapy associated with treatment
      outcome?
AB  - This study examined whether level of exposure to Stimulant Abuser Groups to
      Engage in 12-Step (STAGE-12), a 12-Step facilitative therapy, is related to
      treatment outcome. Data were from a large National Drug Abuse Treatment Clinical
      Trials Network (CTN) study comparing STAGE-12 combined with treatment-as-usual
      (TAU) to TAU alone. These analyses include only those randomized to STAGE-12
      (n=234). Assessments occurred at baseline and 30, 60, 90, and 180 days following
      randomization. High-exposure patients (n=158; attended at least 2 of 3
      individual, and 3 of 5 group, sessions), compared to those with less exposure
      (n=76), demonstrated: (1) higher odds of self-reported abstinence from, and lower
      rates of, stimulant and non-stimulant drug use; (2) lower probabilities of
      stimulant-positive urines; (3) more days of attending and lower odds of not
      attending 12-Step meetings; (4) greater likelihood of reporting no drug problems;
      (5) more days of duties at meetings; and (6) more types of 12-Step activities.
      Many of these differences declined over time, but several were still significant
      by the last follow-up. Treatment and research implications are discussed.

PMID- 25064422
TI  - Safety and tolerability of slow-release oral morphine versus methadone in the
      treatment of opioid dependence.
AB  - Opioid substitution treatment (OST) for opioid dependence may be limited by
      adverse events (AEs). Increasing the range of therapeutic options optimizes
      outcomes and facilitates patient management. An international, multi-center, two
      phase study investigated the efficacy and safety of slow-release oral morphine
      (SROM) versus methadone in patients receiving methadone therapy for opioid
      dependence. In phase 1 (two way cross-over, 11 weeks each period) patients were
      randomized to SROM or methadone oral solution. In phase 2 (25 weeks), patients
      continued treatment with SROM (group A) or switched from methadone to SROM (group
      B). In total, 211 out of 276 completed phase 1 and 198 entered phase 2 (n=95
      group A, n=103 group B). Treatment with both SROM and methadone was well
      tolerated. However, the mean QTc-interval associated with methadone was
      significantly longer than that under SROM. Higher treatment satisfaction, fewer
      cravings for heroin, and lower mental stress were reported with SROM. This study
      adds a significant further weight of evidence that SROM is an effective and well
      tolerated long-term maintenance treatment for opioid dependence with a beneficial
      risk profile compared to methadone regarding cardiac effects and supports its
      clinical utility.

PMID- 25064423
TI  - History of Korean Neurosurgery.
AB  - The year 2012 was the 50th anniversary of the Korean Neurosurgical Society, and
      in 2013, the 15th World Congress of Neurosurgery took place in Seoul, Korea.
      Thus, it is an appropriate occasion to introduce the world to the history of the
      Korean Neurosurgical Society and the foundation, development, and growth of
      Korean neurosurgery. Historical materials and pictures were collected and
      reviewed from the history book and photo albums of the Korean Neurosurgical
      Society. During the last 50 years, the Korean Neurosurgical Society and Korean
      neurosurgery have developed and grown enormously not only in quantity but also in
      quality. In every aspect, the turning point from the old to the new era of the
      Korean Neurosurgical Society and Korean neurosurgery was the year 1980. 

PMID- 25064424
TI  - Resection of sporadic spinal hemangioblastomas.

PMID- 25064425
TI  - Dynamic stability of superior vs. inferior body segments in individuals with
      transtibial amputation walking in destabilizing environments.
AB  - Interestingly, young and highly active people with lower limb amputation appear
      to maintain a similar trunk and upper body stability during walking as able
      bodied individuals. Understanding the mechanisms underlying how this stability is
      achieved after lower-leg amputation is important to improve training regimens for
      improving walking function in these patients. This study quantified how superior
      (i.e., head, trunk, and pelvis) and inferior (i.e., thigh, shank, and feet)
      segments of the body respond to continuous visual or mechanical perturbations
      during walking. Nine persons with transtibial amputation (TTA) and 12 able-bodied
      controls (AB) walked on a 2 m * 3 m treadmill in a Computer Assisted
      Rehabilitation Environment (CAREN). Subjects were perturbed by continuous pseudo
      random mediolateral movements of either the treadmill platform or the visual
      scene. TTA maintained a similar local and orbital stability in their superior
      body segments as AB throughout both perturbation types. However, for their
      inferior body segments, TTA subjects exhibited greater dynamic instability during
      perturbed walking. In TTA subjects, these increases in instability were even more
      pronounced in their prosthetic limb compared to their intact leg. These findings
      demonstrate that persons with unilateral lower leg amputation maintain upper body
      stability in spite of increased dynamic instability in their impaired lower leg.
      Thus, transtibial amputation does significantly impair sensorimotor function,
      leading to substantially altered dynamic movements of their lower limb segments.
      However, otherwise relatively healthy patients with unilateral transtibial
      amputation appear to retain sufficient remaining sensorimotor function in their
      proximal and contralateral limbs to adequately compensate for their impairment.

PMID- 25064426
TI  - Does adiposity affect muscle function during walking in children?
AB  - The biomechanical mechanisms responsible for the altered gait in obese children
      are not well understood, particularly as they relate to increases in adipose
      tissue. The purpose of this study was to test the hypotheses that as body-fat
      percentage (BF%) increased: (1) knee flexion during stance would decrease while
      pelvic obliquity would increase; (2) peak muscle forces normalized to lean-weight
      would increase for gluteus medius, gastrocnemius, and soleus, but decrease for
      the vasti; and (3) the individual muscle contributions to center of mass (COM)
      acceleration in the direction of their primary function(s) would not change for
      gluteus medius, gastrocnemius, and soleus, but decrease for the vasti. We scaled
      a musculoskeletal model to the anthropometrics of each participant (n=14, 8-12
      years old, BF%: 16-41%) and estimated individual muscle forces and their
      contributions to COM acceleration. BF% was correlated with average knee flexion
      angle during stance (r=-0.54, p=0.024) and pelvic obliquity range of motion
      (r=0.78, p<0.001), as well as with relative vasti (r=-0.60, p=0.023), gluteus
      medius (r=0.65, p=0.012) and soleus (r=0.59, p=0.026) force production.
      Contributions to COM acceleration from the vasti were negatively correlated to
      BF% (vertical-- r=-0.75, p=0.002, posterior-- r=-0.68, p=0.008), but there were
      no correlation between BF% and COM accelerations produced by the gastrocnemius,
      soleus and gluteus medius. Therefore, we accept our first, partially accept our
      second, and accept our third hypotheses. The functional demands and relative
      force requirements of the hip abductors during walking in pediatric obesity may
      contribute to altered gait kinematics.

PMID- 25064427
TI  - Finite element simulation of the mechanical impact of computer work on the carpal
      tunnel syndrome.
AB  - Carpal tunnel syndrome (CTS) is a clinical disorder resulting from the
      compression of the median nerve. The available evidence regarding the association
      between computer use and CTS is controversial. There is some evidence that
      computer mouse or keyboard work, or both are associated with the development of
      CTS. Despite the availability of pressure measurements in the carpal tunnel
      during computer work (exposure to keyboard or mouse) there are no available data
      to support a direct effect of the increased intracarpal canal pressure on the
      median nerve. This study presents an attempt to simulate the direct effects of
      computer work on the whole carpal area section using finite element analysis. A
      finite element mesh was produced from computerized tomography scans of the carpal
      area, involving all tissues present in the carpal tunnel. Two loading scenarios
      were applied on these models based on biomechanical data measured during computer
      work. It was found that mouse work can produce large deformation fields on the
      median nerve region. Also, the high stressing effect of the carpal ligament was
      verified. Keyboard work produced considerable and heterogeneous elongations along
      the longitudinal axis of the median nerve. Our study provides evidence that
      increased intracarpal canal pressures caused by awkward wrist postures imposed
      during computer work were associated directly with deformation of the median
      nerve. Despite the limitations of the present study the findings could be
      considered as a contribution to the understanding of the development of CTS due
      to exposure to computer work. 

PMID- 25064428
TI  - Expression and purification of half-smooth tongue sole (Cynoglossus semilaevis)
      CSDAZL protein.
AB  - The csdazl gene is a sex related gene of half-smooth tongue sole (Cynoglossus
      semilaevis). Our research group have cloned full length cDNA of csdazl, and
      studied its expression pattern. To get the further information of csdazl, we
      constructed a prokaryotic expression plasmid, pET-32a-CSDAZL, expressed in
      Escherichia coli BL21 and purified the fusion protein by His Trap. In order to
      detect the biological activity of the fusion protein, we injected the protein
      with liposome into fish, and detected other sex-related genes' mRNA expression.
      The results showed that the expression levels of half-smooth tongue sole female
      related genes Cyp19a and Foxl2 significantly decreased between 6 and 24 h;
      however, both genes' expressions returned to their normal levels 72 h after
      injection, indicating that recombinant CSDAZL protein could down-regulated the
      expression of female-related genes, Foxl2 and Cyp19a genes, implying that the
      fusion protein has biological activity and csdazl plays a role in sex
      differentiation by regulating sex related genes' expression.

PMID- 25064429
TI  - Differences in three-dimensional soft tissue changes after upper, lower, or both
      jaw orthognathic surgery in skeletal class III patients.
AB  - The decision is not always straightforward as to which orthognathic procedure is
      best for a good aesthetic result; three-dimensional imaging has brought new
      insight into this topic. The aim of this prospective study was to verify
      objectively whether postoperative changes occur within those regions not directly
      affected by surgical movements of the underlying jaw bones. The study included 83
      young adults with skeletal class III deformities. They were classified into three
      groups according to the type of surgery: bilateral sagittal split osteotomy set
      back of the mandible (BSSO), Le Fort I advancement of the maxilla, or a
      combination of both. Pre- and postoperative optical scans were registered as
      regional best-fits on the areas of the foreheads and both orbits. The shell to
      shell differences were measured and the average distances between the observed
      regions were calculated. As expected, changes were greatest in the regions where
      the underlying bones had been moved, but regardless of the operation performed,
      changes were found over the whole face. Changes in the nose, cheek, and upper lip
      regions in the BSSO group and in the lower lip and chin region in the Le Fort I
      group confirmed the concept of the facial soft tissue mask acting as one unit. 

PMID- 25064430
TI  - MicroRNA as a novel component of the tissue renin angiotensin system.

PMID- 25064431
TI  - Neural reinstatement and the amount of information recollected.
AB  - Recent functional neuroimaging studies have attempted to understand the cognitive
      and neural bases of episodic memory retrieval, as well as the extent to which
      different retrieval judgments reflect qualitative as opposed to continuous
      changes in neural signals. The present study addressed this issue by
      investigating the reinstatement of episodic content according to the amount of
      information available at retrieval. Subjects encoded a series of words in the
      context of three distinct tasks, while a manipulation of presentation duration (4
      or 8s) was also employed. A later recognition memory test was used to segregate
      trials according to whether or not they were accompanied by the recollection of
      details from encoding. Functional MRI data acquired during both the encoding and
      retrieval phases were used in conjunction with multi-voxel pattern-analysis
      (MVPA) to provide a measure of the degree to which encoding-related patterns of
      brain activity were later reactivated (reinstated) at the time of retrieval.
      Critically, the magnitude of reinstatement differed with respect to the encoding
      manipulation, such that reinstatement was stronger for items associated with the
      longer presentation duration. Together with duration-related differences in
      retrieval activity in left posterior parietal cortex, the results provide neural
      evidence for the reinstatement of different amounts of episodic information,
      consistent with the idea that recollection is based on a continuous neural
      signal. 

PMID- 25064432
TI  - Is faster better? Effects of response deadline on ERP correlates of recognition
      memory in younger and older adults.
AB  - Aging studies generally suggest that recollection is impaired whereas familiarity
      based recognition remains relatively preserved in healthy older adults. The
      present event-related potential (ERP) study explores whether age-related
      impairments in recognition memory can be reduced under conditions in which
      recognition decisions are primarily driven by familiarity. Old and young adults
      performed an item recognition task with perceptually rich visual stimuli. A
      response deadline procedure was employed following previous studies which have
      shown that limiting response times attenuates recollection but leaves familiarity
      relatively unaffected. Age effects on memory performance were large in the non
      speeded response condition in which recollection contributes to performance. When
      response time was limited, performance differences between groups were
      negligible. In the non-speeded condition the ERP correlate of recollection was
      not detectable in old adults. Conversely, in the speeded condition ERP correlates
      of familiarity were obtained in both age groups, though attenuated for old
      adults. For old adults in the speeded condition a temporally extended posterior
      negativity was obtained which was more pronounced for low performing
      participants. The results suggest that even though the neural generators of the
      familiarity signal degrade with age, familiarity is an important contributor to
      recognition memory in older adults and can lead to a disproportional benefit in
      memory in conditions designed to specifically enhance familiarity-based
      responding. 

PMID- 25064433
TI  - Effects of substance P during the recovery of hearing function after noise
      induced hearing loss.
AB  - Substance P (SP) is a widely distributed neurotransmitter in living tissues and
      is involved in various repair processes. We investigated the possibility that SP
      may ameliorate cochlear hair cell damage produced by noise exposure. The present
      study examined the effect of SP in protecting the cochlea from noise damage in
      guinea pigs exposed to noise after an infusion of SP into the inner ear. Changes
      in the hearing threshold (auditory brain response, ABR), number of synaptic
      ribbons, and the appearance of the outer hair cells after noise exposure were
      analyzed at 2 severity levels of noise-induced hearing loss. The moderate noise
      induced hearing loss (110dB, 3h) group showed recovery in the ABR threshold over
      time, finally reaching a level slightly above pre-exposure levels, with only
      slight injury to the synaptic ribbons and minimal changes in the appearance of
      the outer hair cells. Our results indicated that in moderate hearing loss, SP
      exhibited a protective effect on the inner ear, both functionally and
      structurally. While the final magnitude of ABR threshold elevation was greater in
      severe noise-induced hearing loss, the synaptic ribbons and outer hair cells
      showed signs of severe damage. 

PMID- 25064434
TI  - The neural generators of the mismatch responses to Mandarin lexical tones: an MEG
      study.
AB  - The present magnetoencephalography study used the cortically constrained minimum
      norm estimates of human brain activity to elucidate functional roles of neural
      generators for detecting different magnitudes of lexical tones changes. A
      multiple-deviant oddball paradigm was used in which the syllable "yi" with a low
      dipping tone (T3) was the common standard sound and the same syllable with a high
      level tone (T1) or a high-rising tone (T2) were the large and small deviant
      sounds, respectively. The data revealed a larger magnetic mismatch field (MMNm)
      for large deviant in the left hemisphere. The source analysis also confirmed that
      the MMNm to lexical tone changes was generated in bilateral superior temporal
      gyri and only the large deviant revealed left lateralization. A set of frontal
      generators was activated at a later time and revealed differential sensitivities
      to the degree of deviance. The left anterior insula, the right anterior cingulate
      cortex, and the right ventral orbital frontal cortex were activated when
      detecting a large deviant, whereas the right frontal-opercular region was
      sensitive to the small deviant. These frontal generators were thought to be
      associated with various top-down mechanisms for attentional modulation. The time
      frequency (TF) analysis showed that large deviants yielded large theta band (5
      7Hz) activity over the left anterior scalp and the left central scalp, while
      small deviants yielded large alpha band activity (9-11Hz) over the posterior
      scalp. The results of TF analyses implied that mechanisms of working memory and
      functional inhibition involved in the processes of acoustic change detection. 

PMID- 25064435
TI  - Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial
      injury and is HMGB1 and TLR4-dependent.
AB  - BACKGROUND & AIMS: Free cholesterol (FC) accumulates in non-alcoholic
      steatohepatitis (NASH) but not in simple steatosis. We sought to establish how FC
      causes hepatocyte injury. METHODS: In NASH-affected livers from diabetic mice,
      subcellular FC distribution (filipin fluorescence) was established by subcellular
      marker co-localization. We loaded murine hepatocytes with FC by incubation with
      low-density lipoprotein (LDL) and studied the effects of FC on JNK1 activation,
      mitochondrial injury and cell death and on the amplifying roles of the high
      mobility-group-box 1 (HMGB1) protein and the Toll-like receptor 4 (TLR4).
      RESULTS: In NASH, FC localized to hepatocyte plasma membrane, mitochondria and
      ER. This was reproduced in FC-loaded hepatocytes. At 40 MUM LDL, hepatocyte FC
      increased to cause LDH leakage, apoptosis and necrosis associated with JNK1
      activation (c-Jun phosphorylation), mitochondrial membrane pore transition,
      cytochrome c release, oxidative stress (GSSG:GSH ratio) and ATP depletion.
      Mitochondrial swelling and crystae disarray were evident by electron microscopy.
      Jnk1(-/-) and Tlr4(-/-) hepatocytes were refractory to FC lipotoxicity; JNK
      inhibitors (1-2 MUM CC-401, CC-930) blocked apoptosis and necrosis. Cyclosporine
      A and caspase-3 inhibitors protected FC-loaded hepatocytes, confirming
      mitochondrial cell death pathways; in contrast, 4-phenylbutyric acid, which
      improves ER folding capacity did not protect FC-loaded hepatocytes. HMGB1 was
      released into the culture medium of FC-loaded wild type (WT) but not Jnk1(-/-) or
      Tlr4(-/-) hepatocytes, while anti-HMGB1 anti-serum prevented JNK activation and
      FC lipotoxicity in WT hepatocytes. CONCLUSIONS: These novel findings show that
      mitochondrial FC deposition causes hepatocyte apoptosis and necrosis by
      activating JNK1; inhibition of which could be a novel therapeutic approach in
      NASH. Further, there is a tight link between JNK1-dependent HMGB1 secretion from
      lipotoxic hepatocytes and a paracrine cytolytic effect on neighbouring
      cholesterol-loaded hepatocytes operating via TLR4.

PMID- 25064436
TI  - Increased survival in hepatocellular carcinoma with iodine-125 implantation plus
      radiofrequency ablation: a prospective randomized controlled trial.
AB  - BACKGROUND & AIMS: The purpose of this study was to evaluate whether use of
      combined radiofrequency ablation (RFA) and percutaneous iodine-125 ((125)I) seed
      implantation results in better progression-free survival compared with the use of
      RFA alone in patients with hepatocellular carcinoma. METHODS: 136 patients were
      randomly assigned to undergo HCC treatment with RFA and percutaneous iodine-125
      seed implantation (RFA-(125)I, n=68) or RFA-only (n=68). A total of 91 patients
      had hepatitis B viral infection in both groups. Rates of tumour recurrence and
      overall survival were evaluated. RESULTS: The probabilities of recurrence at 1-,
      3-, and 5-years were 4.5%, 22.1%, and 39.8% in the RFA-(125)I group; and 14.8%,
      35.3%, and 57.4% in the RFA-only group, respectively. The recurrence rate in the
      RFA-(125)I group was significantly lower than in the RFA-only group (HR, 0.508;
      95% CI, 0.317-0.815; p=0.004 by log-rank test). Local and intrahepatic recurrence
      was significantly lower in the RFA-(125)I group than in the RFA-only group (7.3%
      vs. 22.0%, p=0.012 by log-rank test; 17.6% vs. 32.3%, p=0.041 by log-rank test).
      The probabilities of survival at 1-, 3-, and 5-years were 100%, 86.7%, and 66.1%
      in the RFA-(125)I group and 95.6%, 75.0%, and 47.0% in the RFA-only group,
      respectively. The survival rate in the RFA-(125)I group was significantly better
      than in the RFA-only group (HR, 0.502; 95% CI, 0.313-0.806; p=0.003 by log-rank
      test). Cox regression model indicated that the treatment group and tumour size
      were both recurrence-related and overall survival-related prognostic factors.
      CONCLUSIONS: There were significant differences in overall survival and
      cumulative recurrence between RFA-(125)I and RFA-only for patients with small
      HCCs (?3 cm). Treatment with RFA-(125)I facilitated better local and intrahepatic
      tumour control and long-term survival compared with treatment of RFA alone.
      ClinicalTrials.gov Identifier: NCT01717729.

PMID- 25064438
TI  - In silico screening and study of novel ERK2 inhibitors using 3D QSAR, docking and
      molecular dynamics.
AB  - ERK2 is a dual specificity protein kinase, part of the Ras/Raf/MEK/ERK signal
      transduction cascade. It forms an interesting target for inhibition based on its
      relationship with cell proliferation and oncogenesis. A 3D QSAR pharmacophore
      model (Hypo1) with high correlation (r=0.938) was developed for ERK2 ATP site on
      the basis of experimentally known inhibitors. The model included three hydrogen
      bonds, and one hydrophobic site. Assessment of Hypo1 through Fisher
      randomization, cost analysis, leave one out method and decoy test suggested that
      the model can reliably detect ERK2 inhibitors. Hypo1 has been used for virtual
      screening of potential inhibitors from ZINC, Drug Bank, NCI, Maybridge and
      Chembank databases. Using Hypo1 as a query, databases have been interrogated for
      compounds who meet the pharmacophore features. The resulting hit compounds were
      subject to docking and analysis. Docking and molecular dynamics analysis showed
      that in order to achieve a higher potency compounds have to interact with
      catalytic site, glycine rich loop, Hinge region, Gatekeeper region and ATP site
      entrance residues. We also identified catalytic site and Glycine rich loop as
      important regions to bind by molecules for better potency and selectivity. 

PMID- 25064439
TI  - Reaction analysis and visualization of ReaxFF molecular dynamics simulations.
AB  - ReaxFF MD (Reactive Force Field Molecular Dynamics) is a promising method for
      investigating complex chemical reactions in relatively larger scale molecular
      systems. The existing analysis tools for ReaxFF MD lack the capability of
      capturing chemical reactions directly by analyzing the simulation trajectory,
      which is critical in exploring reaction mechanisms. This paper presents the
      algorithms, implementation strategies, features, and applications of VARxMD, a
      tool for Visualization and Analysis of Reactive Molecular Dynamics. VARxMD is
      dedicated to detailed chemical reaction analysis and visualization from the
      trajectories obtained in ReaxFF MD simulations. The interrelationships among the
      atoms, bonds, fragments, species and reactions are analyzed directly from the
      three-dimensional (3D) coordinates and bond orders of the atoms in a trajectory,
      which are accomplished by determination of atomic connectivity for recognizing
      connected molecular fragments, perception of bond types in the connected
      fragments for molecules or radicals, indexing of all these molecules or radicals
      (chemical species) based on their 3D coordinates and recognition of bond breaking
      or forming in the chemical species for reactions. Consequently, detailed chemical
      reactions taking place between two sampled frames can be generated automatically.
      VARxMD is the first tool specialized for reaction analysis and visualization in
      ReaxFF MD simulations. Applications of VARxMD in ReaxFF MD simulations of coal
      and HDPE (high-density polyethylene) pyrolysis show that VARxMD provides the
      capabilities in exploring the reaction mechanism in large systems with complex
      chemical reactions involved that are difficult to access manually. 

PMID- 25064440
TI  - Identification and in vitro evaluation of new leads as selective and competitive
      glycogen synthase kinase-3beta inhibitors through ligand and structure based drug
      design.
AB  - Glycogen synthase kinase-3beta elicits multi-functional effects on intracellular
      signaling pathways, thereby making the kinase a therapeutic target in multiple
      pathologies. Hence, it is important to selectively inhibit GSK-3beta over
      structurally and biologically similar targets, such as CDK5. The current study
      was designed to identify and evaluate novel ATP-competitive GSK-3beta inhibitors.
      The study was designed to identify new leads by ligand based drug design,
      structure based drug design and in vitro evaluation. The best validated
      pharmacophore model (AADRRR) identified using LBDD was derived from a dataset of
      135 molecules. There were 357 primary hits within the SPECS database using this
      pharmacophore model. A SBDD approach to the GSK-3beta and CDK5 proteins was
      applied to all primary hits, and 5 selective inhibitors were identified for GSK
      3beta. GSK-3beta and CDK5 in vitro kinase inhibition assays were performed with
      these molecules to confirm their selectivity for GSK-3beta. The molecules showed
      IC50 values ranging from 0.825MUM to 1.116MUM and were 23- to 57-fold selective
      for GSK-3beta. Of all the molecules, molecule 3 had the lowest IC50 value of
      0.825MUM. Our research identified molecules possessing benzothiophene,
      isoquinoline, thiazolidinedione imidazo-isoquinoline and quinazolinone scaffolds.
      Potency of these molecules may be due to H-bond interaction with backbone
      residues of Val135, Asp133 and side chain interaction with Tyr134. Selectivity
      over CDK5 may be due to side chain interactions with Asp200, backbone of Val61,
      ionic interaction with Lys60 and pi-cationic interaction with Arg141. These
      selective molecules were also exhibited small atom hydrophobicity and H-bond
      interaction with water molecule. 

PMID- 25064437
TI  - A randomized phase 2b study of peginterferon lambda-1a for the treatment of
      chronic HCV infection.
AB  - BACKGROUND & AIMS: Peginterferon lambda-1a (Lambda) is a type-III interferon with
      similar antiviral activity to alfa interferons but with a diminished extrahepatic
      receptor distribution, reducing the risk for extrahepatic adverse events.
      METHODS: This was a randomized, blinded, actively-controlled, multicentre phase
      2b dose-ranging study in patients chronically infected with HCV genotypes 1-4.
      Treatment-naive patients received Lambda (120/180/240 MUg) or peginterferon alfa
      2a (alfa; 180 MUg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48
      (GT1,4) weeks. RESULTS: Rates of undetectable HCV-RNA at week 12 (complete early
      virologic response [cEVR]; primary end point) were significantly higher in GT1,4
      patients receiving Lambda vs. alfa (170/304, 56% vs. 38/103, 37%); with similar
      cEVR rates for GT2,3 (80/88, 91% vs. 26/30, 87%). Rates of undetectable HCV-RNA
      at week 4 were significantly higher on 180 MUg (15/102, 15% GT1,4; 22/29, 76%
      GT2,3) and 240 MUg (17/104, 16% GT1,4; 20/30, 67% GT2,3) Lambda than alfa (6/103,
      6% GT1,4; 9/30, 30% GT2,3). Sustained virologic responses (post-treatment week
      24) were comparable between Lambda and alfa for GT1,4 (37-46% Lambda; 37% alfa)
      and GT2,3 (60-76% Lambda; 53% alfa). Aminotransferase and/or bilirubin elevations
      were the primary dose-limiting abnormalities for Lambda; a sponsor-mandated 240
      to 180 MUg dose reduction was therefore implemented. Serious adverse events were
      comparable (3-13% Lambda; 3-7% alfa). Grade 3-4 haemoglobin, neutrophil, and
      platelet reductions were lower on Lambda than alfa. Among alfa patients, 28/133
      (21%) had peginterferon and 31/133 (23%) had ribavirin dose reductions for
      haematologic abnormalities vs. 0/392 and 8/392 (2%) on Lambda. Lambda
      demonstrated fewer musculoskeletal (16-28% vs. 47-63%) and influenza-like events
      (8-23% vs. 40-46%) than alfa. CONCLUSION: Lambda was associated with improved or
      similar rates of virologic response with fewer extrahepatic adverse events than
      alfa in chronic HCV infection.

PMID- 25064441
TI  - Possible functions of contextual modulations and receptive field nonlinearities:
      pop-out and texture segmentation.
AB  - When analyzing a visual image, the brain has to achieve several goals quickly.
      One crucial goal is to rapidly detect parts of the visual scene that might be
      behaviorally relevant, while another one is to segment the image into objects, to
      enable an internal representation of the world. Both of these processes can be
      driven by local variations in any of several image attributes such as luminance,
      color, and texture. Here, focusing on texture defined by local orientation, we
      propose that the two processes are mediated by separate mechanisms that function
      in parallel. More specifically, differences in orientation can cause an object to
      "pop out" and attract visual attention, if its orientation differs from that of
      the surrounding objects. Differences in orientation can also signal a boundary
      between objects and therefore provide useful information for image segmentation.
      We propose that contextual response modulations in primary visual cortex (V1) are
      responsible for orientation pop-out, while a different kind of receptive field
      nonlinearity in secondary visual cortex (V2) is responsible for orientation-based
      texture segmentation. We review a recent experiment that led us to put forward
      this hypothesis along with other research literature relevant to this notion. 

PMID- 25064442
TI  - Relationship between HLA-DRB1* 11/15 genotype and susceptibility to multiple
      sclerosis in Iran.
AB  - BACKGROUND & OBJECTIVES: Analysis of the role of different alleles of human
      leukocyte antigen (HLA) in multiple sclerosis (MS) patients is necessary in many
      populations and geographical areas. The aim of the present study was to
      investigate the frequency of HLA-DRB1 genes and its influence on susceptibility
      to MS, comparing with that in control group. DESIGN AND SETTING: Two groups of
      case-control of multiple sclerosis patients referred to clinic at Khatam
      hospitals were studied. The first group consisted of 73 multiple sclerosis
      patients and the second group comprised 40 healthy volunteers with no known
      history of MS, living in Tehran. PATIENTS AND METHODS: The sample population
      consisted of 73 consecutive non-selected patients diagnosed with MS according to
      the McDonald criteria (2010) at the outpatient clinic for multiple sclerosis, 62
      (85%) presented with RRMS and 11 (15%) with SPMS. The frequency of HLA-DRB1
      alleles was determined in 73 MS patients (with age of 18-56) and 40 healthy
      subjects in Iran. These consisted of 57 females and 16 males. HLA-DRB1 allele
      types were identified by polymerase chain reaction products of 24 pair primers
      for low resolution SSP typing (PCR-SSP). RESULTS: The HLA-DRB1* 11/15 genotype
      was detected highest (6 times) in patients compare to normal control population
      (p-value 0.062), whereas the DRB1 4/11 genotype was detected highest (4 times) in
      controls compare to MS patients (p-value 0.033). The data showed that HLA-DRB1*03
      is significantly more in patients compare to control normal people (p-value
      0.0021) as well as DRB1 14 and 16 are significantly more in control normal
      people, compare to MS patients (p-values 0.0789 and 0.035). CONCLUSION: Allele
      frequency among patients with positive history of multiple sclerosis disease
      showed that DRB1 11 allele has a significantly low rate in MS patients with
      positive history compare to other patients. In contrast DRB1 15 allele has a
      significantly high rate in MS patients with positive history compare to other
      patients. The frequencies of other alleles were not significantly different
      between the MS patients and the control group. The frequency of the HLA-DRB1*
      11/15 genotype detected in the present study showed that this genotype is
      partially significant factor for MS susceptibility and development in Iran.

PMID- 25064443
TI  - Uhthoff's phenomena and brain MRI suggesting demyelinating lesions: RIS or CIS? A
      case report.

PMID- 25064444
TI  - The endogenous alpha7 nicotinic acetylcholine receptor antagonist kynurenic acid
      modulates amyloid-beta-induced inflammation in BV-2 microglial cells.
AB  - Amyloid-beta has been shown to interact with the alpha7 nicotinic acetylcholine
      receptor on neuronal cells. Not much is known on the effect on microglial cells
      and whether this effect can be modulated by the endogenous alpha7 nicotinic
      acetylcholine receptor antagonist kynurenic acid. Our aim was to investigate the
      effect of kynurenic acid on amyloid-beta-treated BV-2 microglial cells with
      respect to alpha7 nicotinic acetylcholine receptor expression, cell viability,
      cytokine production and phagocytotic abilities. Therefore BV-2 cells were treated
      with oligomeric or fibrillar forms of amyloid-beta(1-40) and co-treated with
      kynurenic acid. alpha7 nicotinic acetylcholine receptor quantity was investigated
      using Western blotting. Cell viability was assessed by staining cells with
      fluorescein diacetate and propidium iodide. Pro-inflammatory cytokines were
      measured in cell culture supernatants of treated cells with ELISAs; NO with
      Griess reagents and amyloid-beta uptake were investigated with fluorescence
      activated cell sorting and verified by Western blotting. Amyloid-beta nor
      kynurenic acid did have an effect on the protein level of the alpha7 nicotinic
      acetylcholine receptor. Amyloid-Beta induced cell mortality was unchanged after
      addition of kynurenic acid. However, kynurenic acid co-treatment reduced the pro
      inflammatory cytokines tumour necrosis factor-alpha and IL-6 and amyloid-beta
      phagocytosis. We provide evidence for an immunomodulating effect of the
      endogenous alpha7 nicotinic acetylcholine receptor antagonist kynurenic acid. Our
      findings indicate a role for kynurenic acid in amyloid-beta associated
      neuroinflammation in Alzheimer disease.

PMID- 25064445
TI  - Serum biomarkers to evaluate the integrity of the neurovascular unit.
AB  - Biomarkers have the potential to enable the clinicians to screen infants for
      brain injury, monitor progression of disease, identify injured brain regions,
      assess efficacy of neuroprotective therapies, and offer hope to identify the
      timing of the injury, thus shedding light on the potential pathophysiology and
      the most effective therapy. Currently, clinicians do not routinely use biomarkers
      to care for neonates with Neonatal Encephalopathy (NE) and brain injury due to
      prenatal hypoxia-asphyxia. This review will cover potential biomarkers of the
      neurovascular unit in the setting of NE that (i) can help assess the degree or
      severity of encephalopathy at birth; (ii) can help monitor progression of disease
      process and efficacy of neuroprotective therapy; (iii) can help assess
      neurodevelopmental outcome. These biomarkers will be summarized in two
      categories: 1) Specific biomarkers targeting the neurovascular unit such as glial
      fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH
      L1), S100B, and neuron specific enolase (NSE) and 2) general inflammatory
      cytokines, such as interleukin-6 (IL-6), interleukin-1b (IL-1b), and pNF-H, among
      others. 

PMID- 25064446
TI  - Independent and interactive effects of DOF affecting germination 1 (DAG1) and the
      Della proteins GA insensitive (GAI) and Repressor of ga1-3 (RGA) in embryo
      development and seed germination.
AB  - BACKGROUND: The transcription factor DOF AFFECTING GERMINATION1 (DAG1) is a
      repressor of seed germination acting downstream of the master repressor
      PHYTOCROME INTERACTING FACTOR3-LIKE 5 (PIL5). Among others, PIL5 induces the
      expression of the genes encoding the two DELLA proteins GA INSENSITIVE 1 (GAI)
      and REPRESSOR OF ga1-3 (RGA). RESULTS: Based on the properties of gai-t6 and
      rga28 mutant seeds, we show here that the absence of RGA severely increases
      dormancy, while lack of GAI only partially compensates RGA inactivation. In
      addition, the germination properties of the dag1rga28 double mutant are different
      from those of the dag1 and rga28 single mutants, suggesting that RGA and DAG1 act
      in independent branches of the PIL5-controlled germination pathway. Surprisingly,
      the dag1gai-t6 double mutant proved embryo-lethal, suggesting an unexpected
      involvement of (a possible complex between) DAG1 and GAI in embryo development.
      CONCLUSIONS: Rather than overlapping functions as previously suggested, we show
      that RGA and GAI play distinct roles in seed germination, and that GAI interacts
      with DAG1 in embryo development.

PMID- 25064447
TI  - Lung fibrotic tenascin-C upregulation is associated with other extracellular
      matrix proteins and induced by TGFbeta1.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung
      disease of unknown aetiology and poor prognosis, characterized by altered tissue
      repair and fibrosis. The extracellular matrix (ECM) is a critical component in
      regulating cellular homeostasis and appropriate wound healing. The aim of our
      study was to determine the expression profile of highlighted ECM proteins in IPF
      lungs. METHODS: ECM gene and protein expression was analyzed by cDNA microarrays,
      rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary
      fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP)
      and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from
      normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC)
      synthesis. RESULTS: A total of 20 ECM proteins were upregulated and 6 proteins
      downregulated in IPF. TNC was almost undetected in normal lungs and significantly
      upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was
      located specifically in the fibroblastic foci areas of the fibrotic lung with a
      subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci
      content in cHP lungs. Versican and fibronectin glycoproteins were associated with
      TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients
      constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and
      alpha-sma was induced by TGF-beta1 in both fibrotic and normal fibroblasts. TNC
      treatment of normal and fibrotic fibroblasts induced a non-significant increased
      alpha-sma mRNA. CONCLUSIONS: The difference in ECM glycoprotein content in
      interstitial lung diseases could contribute to the development of lung fibrosis.
      The increase of TNC in interstitial areas of fibrotic activity could play a key
      role in the altered wound healing.

PMID- 25064448
TI  - Malonyldialdehyde and glyoxal act differently on low-density lipoproteins and
      endotheliocytes.
AB  - Under some pathological conditions, the natural dicarbonyl compounds can
      accumulate in the blood. The examples are malonyldialdehyde (MDA) formed as a
      secondary product of lipid peroxidation of unsaturated fatty acids during
      atherosclerosis, and glyoxal (GOX), a homolog of MDA, which accumulates during
      glucose autoxidation in patients with diabetes mellitus. This study compared the
      influence of both dicarbonyl compounds on low-density lipoproteins (LDL) and the
      membrane of endotheliocytes. In comparison with GOX, MDA induced more pronounced
      changes in physical and chemical properties of LDL particles. On the other hand,
      GOX-modified LDL particles were more prone to oxidation and aggregation than MDA
      modified LDL. Incubation of endotheliocytes with MDA increased cell mechanical
      stiffness in contrast to incubation with GOX, which decreased it.

PMID- 25064449
TI  - Differential effect of cataract-associated mutations in MAF on transactivation of
      MAF target genes.
AB  - Three mutations in the highly conserved DNA-binding region of c-MAF (R288P,
      K297R, and R299S) are associated with phenotypically distinct forms of autosomal
      dominant congenital cataract. However, the molecular mechanisms underlying this
      phenotypic diversity remain unclear. In this work, we have investigated the
      hypothesis that differential transactivation of MAF target genes could be one
      factor determining the phenotypic differences. Promoter constructs were generated
      for four human crystallin genes with conserved half-site MAF responsive elements
      (MARE). MAF expression constructs were constructed with the wildtype MAF sequence
      and with each of the three known mutations, i.e., R288P (associated with
      pulverulent cataract), K297R (associated with cerulean cataract), and R299S
      (associated with the most severe phenotype, congenital cataract, and microcornea
      syndrome). Transactivation was measured using luciferase reporter assays
      following cotransfection in HEK cells. Responsiveness to wildtype c-MAF was
      established for each of the four crystallin promoter constructs. The same
      constructs were then investigated using c-MAF mutants corresponding to each of
      the three mutations. A differential response was noted for each of the tested
      crystallin genes. The mutation R288P significantly reduced the expression of the
      CRYGA and CRYBA1 constructs but had no significant effect on the other two
      constructs. K297R did not lead to a significant reduction in expression of any of
      the four constructs, although there was a tendency toward reduced expression
      especially for the CRYGA construct. R299S, which is associated with the most
      severe phenotype, congenital cataract, and microcornea syndrome, was associated
      with the most severe overall effect on the transactivation of the four crystallin
      expression constructs. Our findings suggest that differential effects of
      mutations on the transactivation potential of c-MAF could be a molecular
      correlate of the striking genotype-phenotype correlations seen in cataract forms
      caused by mutations in the MAF gene.

PMID- 25064450
TI  - Protective effect of quercetin in ecto-enzymes, cholinesterases, and
      myeloperoxidase activities in the lymphocytes of rats exposed to cadmium.
AB  - The ex vivo and in vitro effects of quercetin on NTPDase, adenosine deaminase
      (ADA), and acetycholinesterase (AChE) activities in lymphocytes, as well as the
      effects of quercetin on butyrylcholinesterase (BChE) activity in serum and
      myeloperoxidase (MPO) activity in plasma were determined in rats. For the ex vivo
      experiment, animals were orally exposed to Cadmium (Cd) for 45 days. Animals were
      divided into eight groups: saline/ethanol, saline/Querc 5 mg/kg, saline/Querc 25
      mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg,
      and Cd/Querc 50 mg/kg. The ex vivo data showed an increase in the ATP and ADP
      hydrolysis and ADA activity in Cd-exposed rats when compared to the control
      group. The treatment with quercetin 25 and 50 mg/kg prevented this increase in
      the ATP and ADP hydrolysis, while the treatment with quercetin 5, 25, and 50
      mg/kg prevented the increase in the ADA activity. AChE, BChE, and MPO activities
      ex vivo presented an increase in the Cd-exposed group when compared to the
      control group, and the treatment with quercetin 5, 25, and 50 mg/kg prevented
      this increase caused by Cd exposure. The in vitro experiment showed that
      quercetin 5, 10, 25, or 50 uM decreased the ADA activity proportionally to the
      increase of the concentrations of quercetin when compared to the control group.
      Thus, we can suggest that the quercetin is able to modulate NTPDase, ADA, AChE,
      and MPO activities and contribute to maintain the levels of ATP, adenosine, and
      acetylcholine normal, respectively, exhibiting potent pro-inflammatory and anti
      inflammatory actions.

PMID- 25064452
TI  - Hollow fibre membrane bioreactors for tissue engineering applications.
AB  - Hollow fibre membrane bioreactors (HFB) provide a novel approach towards tissue
      engineering applications in the field of regenerative medicine. For adherent cell
      types, HFBs offer an in vivo-like microenvironment as each fibre replicates a
      blood capillary and the mass transfer rate across the wall is independent from
      the shear stresses experienced by the cell. HFB also possesses the highest
      surface area to volume ratio of all bioreactor configurations. In theory, these
      factors enable a high quantity of the desired cellular product with less
      population variation, and favourable operating costs. Experimental analyses of
      different cell types and bioreactor designs show encouraging steps towards
      producing a clinically relevant device. This review discusses the basic HFB
      design for cell expansion and in vitro models; compares data produced on
      commercially available systems and addresses the operational differences between
      theory and practice. HFBs are showing some potential for mammalian cell culture
      but further work is needed to fully understand the complexities of cell culture
      in HFBs and how best to achieve the high theoretical cell yields. 

PMID- 25064451
TI  - Activated hedgehog pathway is a potential target for pharmacological intervention
      in biliary tract cancer.
AB  - Hedgehog (Hh) signalling contributes to carcinogenesis and represents a valid
      druggable target in human cancers, possibly also in biliary tract cancer (BTC).
      We analysed the expression of Hh components in BTC using eight heterogeneously
      differentiated cell lines, xenograft tumours and a human tissue microarray. The
      dose-, time- and cell line-dependent effects of two Hh inhibitors (cyclopamine
      and Gant-61) were analysed in vitro for survival, apoptosis, cell cycle
      distribution and possible synergism with conventional chemotherapeutic agents. In
      human BTC samples, the sonic Hh ligand and the Gli1 transcription factor showed
      increased expression in tumours compared to normal adjacent tissue and were
      significantly associated with high tumour grade and positive lymph node status.
      In BTC cell lines, we could confirm the Hh component expression at varying extent
      within the employed cell lines in vitro and in vivo indicating non-canonical
      signalling. Both Hh inhibitors showed dose-dependent cytotoxicity above 5 uM with
      a stronger effect for Gant-61 inducing apoptosis whereas cyclopamine rather
      inhibited proliferation. Cytotoxicity was associated with low cytokeratin
      expression and higher mesenchymal marker expression such as vimentin.
      Additionally, drug combinations of Gant-61 with conventional chemotherapy
      (cisplatin) exerted synergistic effects. In conclusion, Hh pathway is
      significantly activated in human BTC tissue compared to normal adjacent tissue.
      The current data demonstrate for the first time an effective anticancer activity
      of especially Gant-61 in BTC and suggest second generation Hh pathway inhibitors
      as a potential novel treatment strategy in BTC.

PMID- 25064453
TI  - Amphotericin B down-regulates Aggregatibacter actinomycetemcomitans-induced
      production of IL-8 and IL-6 in human gingival epithelial cells.
AB  - Gingival epithelium is the primary barrier against microorganism invasion and
      produces inflammatory cytokines. Amphotericin B, a major antifungal drug, binds
      to cholesterol in the mammalian cell membrane in addition to fungal ergosterol.
      Amphotericin B has been shown to regulate inflammatory cytokines in host cells.
      To investigate the suppressive effect of amphotericin B on the gingival
      epithelium, we examined the expression of interleukin (IL)-8 and IL-6 and
      involvement of MAP kinase in human gingival epithelial cells (HGEC) stimulated by
      Aggregatibacter actinomycetemcomitans. Amphotericin B and the p38 MAP kinase
      inhibitor down-regulated the A. actinomycetemcomitans-induced increase in the
      expression of IL-8 and IL-6 at the mRNA. The ERK inhibitor suppressed the A.
      actinomycetemcomitans-induced IL-8 mRNA expression. Amphotericin B inhibited the
      A. actinomycetemcomitans-induced phosphorylation of ERK and p38 MAP kinase.
      Furthermore, amphotericin B inhibited the A. actinomycetemcomitans-induced
      production of prostaglandin E2. These results suggest that amphotericin B
      regulate inflammatory responses in HGEC. 

PMID- 25064454
TI  - Bone alterations associated with HIV.
AB  - HIV infection and initiation of antiretroviral therapy (ART) have been
      consistently associated with decreased bone mineral density (BMD), with growing
      evidence linking HIV to an increased risk of fracture. This is especially
      concerning with the expanding number of older persons living with HIV.
      Interestingly, recent data suggest that HIV-infected children and youth fail to
      achieve peak BMD, possibly increasing their lifetime risk of fracture.
      Elucidating the causes of the bone changes in HIV-positive persons is challenging
      because of the multifactorial nature of bone disease in HIV, including
      contribution of the virus, immunosuppression, ART toxicity, and traditional
      osteoporosis risk factors, such as age, lower weight, tobacco, and alcohol use.
      Thus, practitioners must recognize the risk of low BMD and fractures and
      appropriately screen patients for osteoporosis if risk factors exist. If
      fractures do occur or elevated fracture risk is detected through screening,
      treatment with bisphosphonate medications appears safe and effective in the
      HIV+population.

PMID- 25064456
TI  - Clinical practice guidelines of the Society for Vascular Surgery (SVS) and the
      American Venous Forum (AVF)--Management of venous leg ulcers. Introduction.

PMID- 25064455
TI  - Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein
      kinase A (PKA) provide new insights into the molecular pathology of
      acrodysostosis.
AB  - Acrodysostosis without hormone resistance is a rare skeletal disorder
      characterized by brachydactyly, nasal hypoplasia, mental retardation and
      occasionally developmental delay. Recently, loss-of-function mutations in the
      gene encoding cAMP-hydrolyzing phosphodiesterase-4D (PDE4D) have been reported to
      cause this rare condition but the pathomechanism has not been fully elucidated.
      To understand the pathogenetic mechanism of PDE4D mutations, we conducted 3D
      modeling studies to predict changes in the binding efficacy of cAMP to the
      catalytic pocket in PDE4D mutants. Our results indicated diminished enzyme
      activity in the two mutants we analyzed (Gly673Asp and Ile678Thr; based on PDE4D4
      residue numbering). Ectopic expression of PDE4D mutants in HEK293 cells
      demonstrated this reduction in activity, which was identified by increased cAMP
      levels. However, the cells from an acrodysostosis patient showed low cAMP
      accumulation, which resulted in a decrease in the phosphorylated cAMP Response
      Element-Binding Protein (pCREB)/CREB ratio. The reason for this discrepancy was
      due to a compensatory increase in expression levels of PDE4A and PDE4B isoforms,
      which accounted for the paradoxical decrease in cAMP levels in the patient cells
      expressing mutant isoforms with a lowered PDE4D activity. Skeletal radiographs of
      10-week-old knockout (KO) rats showed that the distal part of the forelimb was
      shorter than in wild-type (WT) rats and that all the metacarpals and phalanges
      were also shorter in KO, as the name acrodysostosis implies. Like the G-protein
      alpha-stimulatory subunit and PRKAR1A, PDE4D critically regulates the cAMP signal
      transduction pathway and influences bone formation in a way that activity
      compromising PDE4D mutations can result in skeletal dysplasia. We propose that
      specific inhibitory PDE4D mutations can lead to the molecular pathology of
      acrodysostosis without hormone resistance but that the pathological phenotype may
      well be dependent on an over-compensatory induction of other PDE4 isoforms that
      can be expected to be targeted to different signaling complexes and exert
      distinct effects on compartmentalized cAMP signaling.

PMID- 25064457
TI  - Effects of benzophenone-3 exposure on endocrine disruption and reproduction of
      Japanese medaka (Oryzias latipes)--a two generation exposure study.
AB  - Benzophenone-3 (BP-3) has been widely used in sunscreens and cosmetics to protect
      human skin from the harmful effects of UV irradiation. While BP-3 has been
      frequently detected in surface waters, sediments and biota, only limited
      information is available on its in vivo toxicity, particularly in fish. In the
      present study the endocrine disrupting capacity of BP-3 and its underlying
      mechanisms were investigated using Japanese medaka (Oryzias latipes). Adult
      Japanese medaka pairs (F0) were exposed to 0, 4.7, 8.4, 26, or 90 MUg/L (or 0,
      15, 50, 150, or 500 MUg/L of BP-3 based on nominal concentration) for 14 d and
      its effects on sex steroid hormones, and transcription of various associated
      genes were determined. Following additional 14 d of exposure, the F1 eggs
      reproduced were counted and were further exposed to 0, 5.4, 12, or 30 MUg/L of BP
      3 (or 0, 15, 50, or 150 MUg/L based on nominal concentrations) until 30 d after
      hatching. Chemical analysis of the exposed media confirmed transformation of BP-3
      to benzophenone-1 (BP-1), a more potent estrogen agonist. After 14 d of the adult
      fish exposure, plasma concentrations of testosterone (T) significantly increased
      in male fish. The 17beta-estradiol (E2) to T (E2/T) ratio showed significant
      decreases in both male and female fish. Overall down-regulation of gonadal
      steroidogenic genes such as star, cyp11a, cyp17, hsd3b, hsd17b3, and cyp19a was
      also observed. After 28 d of exposure, the daily average egg reproduction per
      female was significantly reduced at 26 MUg/L of BP-3. However, hatchability of F1
      eggs was not affected by continuous exposure. After continued exposure until 30
      dph, juvenile fish showed concentration-dependent decrease of condition factor,
      but mortality was not affected. Our observation clearly indicates that endocrine
      balance and reproduction performance in fish could be affected by MUg/L level
      exposure to BP-3. Consequences of longer term exposure over multi-generations
      warrant further investigation.

PMID- 25064458
TI  - Toxic effects of increased sediment nutrient and organic matter loading on the
      seagrass Zostera noltii.
AB  - As a result of anthropogenic disturbances and natural stressors, seagrass beds
      are often patchy and heterogeneous. The effects of high loads of nutrients and
      organic matter in patch development and expansion in heterogeneous seagrass beds
      have, however, poorly been studied. We experimentally assessed the in situ
      effects of sediment quality on seagrass (Zostera noltii) patch dynamics by
      studying patch (0.35 m diameter) development and expansion for 4 sediment
      treatments: control, nutrient addition (NPK), organic matter addition (OM) and a
      combination (NPK+OM). OM addition strongly increased porewater sulfide
      concentrations whereas NPK increased porewater ammonium, nitrate and phosphate
      concentrations. As high nitrate concentrations suppressed sulfide production in
      NPK+OM, this treatment was biogeochemically comparable to NPK. Sulfide and
      ammonium concentrations differed within treatments, but over a 77 days period,
      seagrass patch survival and expansion were impaired by all additions compared to
      the control treatment. Expansion decreased at porewater ammonium concentrations
      >2,000 MUmol L(-1). Mother patch biomass was not affected by high porewater
      ammonium concentrations as a result of its detoxification by higher seagrass
      densities. Sulfide concentrations >1,000 MUmol L(-1) were toxic to both patch
      expansion and mother patch. We conclude that patch survival and expansion are
      constrained at high loads of nutrients or organic matter as a result of porewater
      ammonium or sulfide toxicity.

PMID- 25064459
TI  - Comet Assay on Daphnia magna in eco-genotoxicity testing.
AB  - Detection of potentially hazardous compounds in water bodies is a priority in
      environmental risk assessment. For the evaluation and monitoring of water
      quality, a series of methodologies may be applied. Among them, the worldwide used
      toxicity tests with organisms of the genus Daphnia is one of the most powerful.
      In recent years, some attempts were made to utilize Daphnia magna in genotoxicity
      testing as many of the new environmental contaminants are described as DNA
      damaging agents in aquatic organisms. The aim of this research was to develop a
      highly standardized protocol of the Comet Assay adapted for D. magna, especially
      regarding the isolation of cells derived from the same tissue (haemolymph) from
      newborn organisms exposed in vivo. Several methods for haemolymph extraction and
      different Comet Assay parameters were compared. Electrophoretic conditions were
      adapted in order to obtain minimum DNA migration in cells derived from untreated
      organisms and, at the same time, maximum sensitivity in specimens treated with
      known genotoxicants (CdCl2 and H2O2). Additional tests were performed to
      investigate if life-history traits of the cladoceran (such as the age of adult
      organisms that provide newborns, the clutch size of origin, the number of
      generations reared in standard conditions) and the water composition as well,
      might influence the response of the assay. This study confirms the potential
      application of the Comet Assay in D. magna for assessing genotoxic loads in
      aqueous solution. The newly developed protocol could integrate the acute toxicity
      bioassay, thus expanding the possibility of using this model species in
      freshwater monitoring (waters, sediment and soil elutriates) and is in line with
      the spirit of the EU Water Framework Directive in reducing the number of
      bioassays that involve medium-sized species. 

PMID- 25064460
TI  - Tigecycline for severe Clostridium difficile infection.
AB  - Limited data suggest that tigecycline may be of value in the treatment of
      Clostridiumdifficile infection. We reviewed our experience using tigecycline to
      treat severe c. difficile and compared outcomes to similarly ill patients who did
      not receive tigecycline. We found no difference between the groups. Further study
      is needed before tigecycline can be recommended for use in severe C. difficile
      infection. 

PMID- 25064461
TI  - Dopaminergic neuron destruction reduces hippocampal serotonin 1A receptor uptake
      of trans-[(18)F]Mefway.
AB  - The purpose of the present study is to investigate the relationship between
      dopaminergic neuron destruction and 5-HT system changes in a hemiparkinsonian rat
      model. We performed PET imaging studies with trans-[(18)F]Mefway in a
      hemiparkinsonian model of unilateral 6-hydroxydopamine (6-OHDA) rats. Region-of
      interests (ROIs) were drawn in the hippocampus (HP) and cerebellum (CB). HP
      uptake, the ratios of specific binding to non-specific binding in the HP, and non
      displaceable binding potential (BPND) in the HP were compared between 6-OHDA and
      control rats. As a result, unilateral 6-OHDA-lesioned rats exhibited significant
      bilateral reduction of HP uptake and trans-[(18)F]Mefway BPND compared to the
      intact control group. Therefore, the results demonstrate that destruction of the
      dopaminergic system causes the reduction of the serotonergic system. 

PMID- 25064462
TI  - RhoA/rho kinase signaling reduces connexin43 expression in high glucose-treated
      glomerular mesangial cells with zonula occludens-1 involvement.
AB  - RhoA/Rho kinase (ROCK) signaling has been suggested to be involved in diabetic
      nephropathy (DN) pathogenesis. Altered expression of connexin43 (Cx43) has been
      found in kidneys of diabetic animals. Both of them have been found to regulate
      nuclear factor kappa-B (NF-kappaB) activation in high glucose-treated glomerular
      mesangial cells (GMCs). The aim of this study was to investigate the relationship
      between RhoA/ROCK signaling and Cx43 in the DN pathogenesis. We found that
      upregulation of Cx43 expression inhibited NF-kappaB p65 nuclear translocation
      induced by RhoA/ROCK signaling in GMCs. Inhibition of RhoA/ROCK signaling
      attenuated the high glucose-induced decrease in Cx43. F-actin accumulation and an
      enhanced interaction between zonula occludens-1 (ZO-1) and Cx43 were observed in
      high glucose-treated GMCs. ZO-1 depletion or disruption of F-actin formation also
      inhibited the reduction in Cx43 protein levels induced by high glucose. In
      conclusion, activated RhoA/ROCK signaling induces Cx43 degradation in GMCs
      cultured in high glucose, depending on F-actin regulation. Increased F-actin
      induced by RhoA/ROCK signaling promotes the association between ZO-1 and Cx43,
      which possibly triggered Cx43 endocytosis, a mechanism of NF-kappaB activation in
      high glucose-treated GMCs.

PMID- 25064464
TI  - Fosinopril improves the electrophysiological characteristics of left ventricular
      hypertrophic myocardium in spontaneously hypertensive rats.
AB  - This study investigated the effects of fosinopril on the electrophysiological
      characteristics of the left ventricular hypertrophic myocardium in spontaneously
      hypertensive rats (SHRs). Twenty-four 10-week-old male SHRs were divided into
      fosinopril and non-fosinopril groups (n = 12 each). Twelve 10-week-old Wistar
      Kyoto rats were used a control group. Left ventricular mass index and ventricular
      fibrillation threshold (VFT) were measured after 8 weeks of fosinopril or saline
      treatment. L-type calcium current (I CaL), sodium current (I Na), and transient
      outward potassium current (I to) were measured in left ventricular myocytes after
      8 weeks of fosinopril or saline treatment using the whole-cell patch-clamp
      technique. VFT was higher in the fosinopril group than in the non-fosinopril
      group (17.5 +/- 1.2 mA vs. 15.6 +/- 1.1 mA, P < 0.01). The density of I CaL was
      lower in the fosinopril group than in the non-fosinopril group (-7.17 +/- 0.13
      pA/pF vs. -7.87 +/- 0.13 pA/pF, P < 0.05). The density of I to was higher in the
      fosinopril group than in the non-fosinopril group (14.46 +/- 0.28 pA/pF vs. 12.66
      +/- 0.25 pA/pF, P < 0.05). I to was positively correlated with VFT (r = 0.90, P <
      0.001) and was found to be associated independently with VFT (P < 0.001).
      Fosinopril improves the electrophysiological characteristics of the left
      ventricular hypertrophic myocardium in SHRs.

PMID- 25064463
TI  - TGFbeta loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of
      esophageal cell invasion.
AB  - The TGFbeta signaling pathway is essential to epithelial homeostasis and is often
      inhibited during progression of esophageal squamous cell carcinoma. Recently, an
      important role for TGFbeta signaling has been described in the crosstalk between
      epithelial and stromal cells regulating squamous tumor cell invasion in mouse
      models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFbeta
      signaling, in either compartment, leads to HNSCC however, the mechanisms involved
      are not well understood. Using organotypic reconstruct cultures (OTC) to model
      the interaction between epithelial and stromal cells that occur in dysplastic
      lesions, we show that loss of TGFbeta signaling promotes an invasive phenotype in
      both fibroblast and epithelial compartments. Employing immortalized esophageal
      keratinocytes established to reproduce common mutations of esophageal squamous
      cell carcinoma, we show that treatment of OTC with inhibitors of TGFbeta
      signaling (A83-01 or SB431542) enhances invasion of epithelial cells into a
      fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83-01 is
      independent of proliferation but relies on protease activity and expression of
      ADAMTS-1 and can be altered by matrix density. This invasion was associated with
      increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF
      and TGFalpha. Altering EGF signaling prevented or induced epithelial cell
      invasion in this model. Loss of expression of the TGFbeta target gene ROBO1
      suggested that chemorepulsion may regulate keratinocyte invasion. Taken together,
      our data show increased invasion through inhibition of TGFbeta signaling altered
      epithelial-fibroblasts interactions, repressing markers of activated fibroblasts,
      and altering integrin-fibronectin interactions. These results suggest that
      inhibition of TGFbeta signaling modulates an array of pathways that combined
      promote multiple aspects of tumor invasion. 

PMID- 25064465
TI  - Effect of surface modification by nitrogen ion implantation on the
      electrochemical and cellular behaviors of super-elastic NiTi shape memory alloy.
AB  - The aim of this investigation was to enhance the biological behavior of NiTi
      shape memory alloy while preserving its super-elastic behavior in order to
      facilitate its compatibility for application in human body. The surfaces of NiTi
      samples were bombarded by three different nitrogen doses. Small-angle X-ray
      diffraction was employed for evaluating the generated phases on the bombarded
      surfaces. The electrochemical behaviors of the bare and surface-modified NiTi
      samples were studied in simulated body fluid (SBF) using electrochemical
      impedance and potentio-dynamic polarization tests. Ni ion release during a 2
      month period of service in the SBF environment was evaluated using atomic
      absorption spectrometry. The cellular behavior of nitrogen-modified samples was
      studied using fibroblast cells. Furthermore, the effect of surface modification
      on super-elasticity was investigated by tensile test. The results showed the
      improvement of both corrosion and biological behaviors of the modified NiTi
      samples. However, no significant change in the super-elasticity was observed.
      Samples modified at 1.4E18 ion cm(-2) showed the highest corrosion resistance and
      the lowest Ni ion release. 

PMID- 25064466
TI  - Limits to understory plant restoration following fuel-reduction treatments in a
      pinon-juniper woodland.
AB  - National fuel-reduction programs aim to reduce the risk of wildland fires to
      human communities and to restore forest and rangeland ecosystems to resemble
      their historical structure, function, and diversity. There are a number of
      factors, such as seed bank dynamics, post-treatment climate, and herbivory, which
      determine whether this latter goal may be achieved. Here, we examine the short
      term (2 years) vegetation response to fuel-reduction treatments (mechanical
      mastication, broadcast burn, and pile burn) and seeding of native grasses on
      understory vegetation in an upland pinon-juniper woodland in southeast Utah. We
      also examine how wildlife herbivory affects the success of fuel-reduction
      treatments. Herbaceous cover increased in response to fuel-reduction treatments
      in all seeded treatments, with the broadcast burn and mastication having greater
      increases (234 and 160 %, respectively) in herbaceous cover than the pile burn
      (32 %). In the absence of seeding, herbaceous cover only increased in the
      broadcast burn (32 %). Notably, fuel-reduction treatments, but not seeding,
      strongly affected herbaceous plant composition. All fuel-reduction treatments
      increased the relative density of invasive species, especially in the broadcast
      burn, which shifted the plant community composition from one dominated by
      perennial graminoids to one dominated by annual forbs. Herbivory by wildlife
      reduced understory plant cover by over 40 % and altered plant community
      composition. If the primary management goal is to enhance understory cover while
      promoting native species abundance, our study suggests that mastication may be
      the most effective treatment strategy in these upland pinon-juniper woodlands.
      Seed applications and wildlife exclosures further enhanced herbaceous cover
      following fuel-reduction treatments.

PMID- 25064467
TI  - PCP-induced deficits in murine nest building activity: employment of an
      ethological rodent behavior to mimic negative-like symptoms of schizophrenia.
AB  - Schizophrenia is a severe psychiatric disorder characterized by three symptom
      domains, positive (hallucinations, obsession), negative (social withdrawal,
      apathy, self-neglect) and cognitive (impairment in attention, memory and
      executive function). Whereas current medication ameliorates positive
      symptomatology, negative symptoms as well as cognitive dysfunctions remain
      untreated. The development of improved therapies for negative symptoms has proven
      particularly difficult, in part due to the inability of mimicking these in
      rodents. Here, we address the predictive validity of combining an ethologically
      well preserved behavior in rodents, namely nest building activity, with an
      established animal model of schizophrenia, the sub-chronic PCP model, for
      negative symptoms. Decline in rodent nesting activity has been suggested to
      mirror domains of negative symptoms of schizophrenia, including social
      withdrawal, anhedonia and self-neglect, whereas repeated treatment with the NMDAR
      antagonist PCP induces and exacerbates schizophrenia-like symptoms in rodents and
      human subjects. Using a back-translational approach of pharmacological
      validation, we tested the effects of two agents targeting the nicotinic alpha7
      receptor (EVP-6124 and TC-5619) that were reported to exert some beneficial
      effect on negative symptoms in schizophrenic patients. Sub-chronic PCP treatment
      resulted in a significant nest building deficit in mice and treatment with EVP
      6124 and TC-5619 reversed this PCP-induced deficit. In contrast, the atypical
      antipsychotic drug risperidone remained ineffective in this assay. In addition,
      EVP-6124, TC-5619 and risperidone were tested in the Social Interaction Test
      (SIT), an assay suggested to address negative-like symptoms. Results obtained in
      SIT were comparable to results in the nest building test (NEST). Based on these
      findings, we propose nest building in combination with the sub-chronic PCP model
      as a novel approach to assess negative-like symptoms of schizophrenia in rodents.

PMID- 25064468
TI  - MicroRNA expression profile of bromocriptine-resistant prolactinomas.
AB  - MicroRNAs (miRNA) have been implicated in the resistance of tumors to
      chemotherapy. However, little is known about miRNA expression in bromocriptine
      resistant prolactinomas. In this study, 23 prolactinoma samples were classified
      as bromocriptine-sensitive or -resistant according to the clinical definition of
      bromocriptine resistance, and their miRNA expression profiles were determined
      using Solexa sequencing. We found 41 miRNAs that were differentially expressed
      between the two groups, and 12 of these were validated by stem-loop qRT-PCR. Hsa
      mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa
      mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa
      mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant
      prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
      Furthermore, silencing of mir-93 significantly increased the sensitivity of MMQ
      cells to dopamine agonist treatment. Mir-93 directly affected p21 expression in
      MMQ cells by targeting the 3'-UTR. Our study is the first to identify a miRNA
      expression profile associated with bromocriptine-resistant prolactinoma. 

PMID- 25064469
TI  - Assessing the potential impact of increased participation in higher education on
      mortality: evidence from 21 European populations.
AB  - Although higher education has been associated with lower mortality rates in many
      studies, the effect of potential improvements in educational distribution on
      future mortality levels is unknown. We therefore estimated the impact of
      projected increases in higher education on mortality in European populations. We
      used mortality and population data according to educational level from 21
      European populations and developed counterfactual scenarios. The first scenario
      represented the improvement in the future distribution of educational attainment
      as expected on the basis of an assumption of cohort replacement. We estimated the
      effect of this counterfactual scenario on mortality with a 10-15-year time
      horizon among men and women aged 30-79 years using a specially developed tool
      based on population attributable fractions (PAF). We compared this with a second,
      upward levelling scenario in which everyone has obtained tertiary education. The
      reduction of mortality in the cohort replacement scenario ranged from 1.9 to
      10.1% for men and from 1.7 to 9.0% for women. The reduction of mortality in the
      upward levelling scenario ranged from 22.0 to 57.0% for men and from 9.6 to 50.0%
      for women. The cohort replacement scenario was estimated to achieve only part (4
      25% (men) and 10-31% (women)) of the potential mortality decrease seen in the
      upward levelling scenario. We concluded that the effect of on-going improvements
      in educational attainment on average mortality in the population differs across
      Europe, and can be substantial. Further investments in education may have
      important positive side-effects on population health. 

PMID- 25064470
TI  - Postnatal development of dendritic structure of layer III pyramidal neurons in
      the medial prefrontal cortex of marmoset.
AB  - In the primate cerebral cortex, dendritic spines rapidly increase in number after
      birth up to infancy or mid-childhood, and then decrease towards adulthood.
      Abnormalities in these processes accompany several psychiatric disorders. In this
      study, we examined developmental changes of basal dendrites and spines of layer
      III pyramidal cells in the medial prefrontal cortex (mPFC) of the common
      marmoset. The mPFC consists of several areas with distinct features in layer
      organization, histochemistry, connections, and, in humans, vulnerability to
      psychiatric disorders. We selected three areas for examination: granular
      dorsomedial prefrontal (area 8B/9), dysgranular ventromedial prefrontal (area
      14r), and agranular anterior cingulate (area 24) cortices. Dendritic field areas,
      lengths, number of branching points, and total spine number reached a peak at 2-3
      postnatal months in all three areas. However, the profiles of spine formation and
      pruning differed across the three areas with different degrees of granularity;
      the amount of spine loss from the peak to adulthood was less in areas 24 (33%)
      and 14r (29%) than in area 8B/9 (43%). Disturbance of this modest spine pruning
      in the less granular cortical areas may lead to an excessive loss of spines
      reported for areas 24 and 14r of schizophrenic patients.

PMID- 25064471
TI  - Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy
      for central lung tumors.
AB  - BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) to central lung
      tumors can cause esophageal toxicity, but little is known about the incidence or
      risk factors. We reviewed central lung SBRT patients to identify dosimetric
      factors predictive of esophageal toxicity. MATERIALS AND METHODS: We assessed
      esophageal toxicity in 125 SBRT patients. Using biological equivalent doses with
      alpha/beta=10 Gy (BED10), dose-volume histogram variables for the esophagus (Dv
      and Vd) were assessed for correlation with grade ?2 acute toxicity. RESULTS:
      Incidence of grade ?2 acute toxicity was 12% (n=15). Highly significant logistic
      models were generated for D5cc and Dmax (p<0.001). To keep the complication rate
      <20%, the model requires that D5cc?26.3 BED10. At 2 years, the probability of
      complication with BED10D5cc>14.4 Gy was 24%, compared to 1.6% if ?14.4 Gy.
      CONCLUSIONS: This novel analysis provides guidelines to predict acute esophageal
      toxicity in lung SBRT. Dose to the hottest 5cc and Dmax of the esophagus were the
      best predictors of toxicity. Converting the BED10 limits to physical doses, D5cc
      to the esophagus should be kept less than 16.8, 18.1 and 19.0 Gy for 3, 4, and 5
      fractions, respectively, to keep the acute toxicity rate <20%.

PMID- 25064472
TI  - Multicentre validation of IMRT pre-treatment verification: comparison of in-house
      and external audit.
AB  - BACKGROUND AND PURPOSE: We performed a multicentre intercomparison of IMRT
      optimisation and dose planning and IMRT pre-treatment verification methods and
      results. The aims were to check consistency between dose plans and to validate
      whether in-house pre-treatment verification results agreed with those of an
      external audit. MATERIALS AND METHODS: Participating centres used two mock cases
      (prostate and head and neck) for the intercomparison and audit. Compliance to
      dosimetric goals and total number of MU per plan were collected. A simple quality
      index to compare the different plans was proposed. We compared gamma index pass
      rates using the centre's equipment and methodology to those of an external audit.
      RESULTS: While for the prostate case, all centres fulfilled the dosimetric goals
      and plan quality was homogeneous, that was not the case for the head and neck
      case. The number of MU did not correlate with the plan quality index. Pre
      treatment verifications results of the external audit did not agree with those of
      the in-house measurements for two centres: being within tolerance for in-house
      measurements and unacceptable for the audit or the other way round. CONCLUSIONS:
      Although all plans fulfilled dosimetric constraints, plan quality is highly
      dependent on the planner expertise. External audits are an excellent tool to
      detect errors in IMRT implementation and cannot be replaced by intercomparison
      using results obtained by centres.

PMID- 25064473
TI  - HPV prevalence and genotype distribution in a population-based split-sample study
      of well-screened women using CLART HPV2 human papillomavirus genotype microarray
      system.
AB  - BACKGROUND: Human papillomavirus (HPV) genotyping assays are becoming
      increasingly attractive for use in mass screening, as they offer a possibility to
      integrate HPV screening with HPV vaccine monitoring, thereby generating a synergy
      between the two main modes of cervical cancer prevention. The Genomica CLART HPV2
      assay is a semi-automated PCR-based microarray assay detecting 35 high-risk and
      low-risk HPV genotypes. However, few reports have described this assay in
      cervical screening. An aim of the present study, Horizon, was to assess the
      prevalence of high-risk HPV infections in Copenhagen, Denmark, an area with a
      high background risk of cervical cancer where women aged 23-65 years are targeted
      for organized screening. METHODS: Material from 5,068 SurePath samples of women
      participating in routine screening and clinical follow-up of cervical
      abnormalities was tested using liquid based cytology, CLART HPV2 and Hybrid
      Capture 2 (HC2). RESULTS: At least one of the 35 defined genotypes was detected
      by CLART in 1,896 (37%) samples. The most frequent high-risk genotypes were HPV
      16 (7%), HPV 52 (5%), and HPV 31 (4%). The most frequent low-risk genotypes were
      HPV 53 (5%), HPV 61 (4%), and HPV 66 (3%). Among 4,793 women targeted by the
      screening program (23-65 years), 1,166 (24%) tested positive for one or more of
      the 13 high-risk genotypes. This proportion decreased from 40% at age 23-29 years
      to 10% at age 60-65 years. On HC2, 1,035 (20%) samples were positive for any high
      risk and thus CLART showed a higher analytical sensitivity for 13 high-risk HPV
      genotypes than HC2, and this was found in all age-groups and in women normal
      cytology. CONCLUSIONS: CLART performed well with a positive reproducibility for
      high-risk genotypes of 86%, and a negative reproducibility of 97%. This report
      furthermore updates the genotype distribution in Denmark prior to the inclusion
      of the HPV-vaccinated cohorts into the screening program, and as such represents
      a valuable baseline for future vaccine impact assessment.

PMID- 25064474
TI  - Possible Tyromyces fissilis (Basidiomycota, Polyporales) co-infection in a lung
      transplant recipient.
AB  - Invasive fungal diseases are severe complication of the lung transplant patients'
      follow-up as they are increasing the risk of rejection. We report a patient who
      developed possible Tyromyces fissilis co-infection during graft rejection episode
      2 years after bilateral lung transplantation for cystic fibrosis. The fungus was
      detected using conventional culture methods as a filamentous basidiomycete and
      further placed to T. fissilis species based on internal transcribed spacer (ITS)
      rDNA sequences. The patient was treated according to the susceptibility testing
      results by voriconazole in combination with the anti-rejection therapy and
      recovered completely within few weeks. This is, to our knowledge, the first
      published case report of T. fissilis as a possible causative agent of an
      infection/rejection episode in a lung transplant recipient. 

PMID- 25064475
TI  - Service quality assessment of a referral hospital in southern Iran with SERVQUAL
      technique: patients' perspective.
AB  - BACKGROUND: Providing services to patients according to their expectations and
      needs is necessary for the success of an organization in order to remain in the
      competitive market. Recognizing these needs and expectations is an important step
      in offering high quality services. This study was designed to determine the
      service quality gap of the main hospital of Hormozgan province. METHODS: This
      cross sectional study was conducted in 2013 in Bandar Abbas ShahidMohammadi
      Hospital in the south of Iran. All 96 participants of this study were provided by
      SERVQUAL questionnaire. Data was analyzed by Wilcoxon and Kruskal-Wallis tests.
      RESULTS: Service quality gaps were seen in all five service quality dimensions
      and the overall quality of service. The mean of quality perception score and
      quality expectation score was 3.44 +/- 0.693 and 4.736 +/- 0.34, respectively.
      The highest perception was in assurance dimension and the highest expectation was
      in Responsiveness and assurance dimensions. Also, the lowest perception was in
      responsiveness dimension and the lowest expectation was about empathy. In this
      study, 56.1% of participants defined the quality of services as average.
      CONCLUSION: According to the results, this hospital was not able to meet
      patients' expectations completely. Therefore, action must be taken to decrease
      the gap between the perception and expectation of the patients.

PMID- 25064476
TI  - A novel electrospun-aligned nanoyarn-reinforced nanofibrous scaffold for tendon
      tissue engineering.
AB  - An electrospun-aligned nanoyarn-reinforced nanofibrous scaffold (NRS) was
      developed for tendon tissue engineering to improve mechanical strength and cell
      infiltration. The novel scaffold composed of aligned nanoyarns and random
      nanofibers was fabricated via electrospinning using a two-collector system. The
      aim of the present study was to investigate three different types of electrospun
      scaffolds (random nanofibrous scaffold, aligned nanofibrous scaffold and NRS)
      based on silk fibroin (SF) and poly(l-lactide-co-caprolactone) blends.
      Morphological analysis demonstrated that the NRS composed of aligned nanoyarns
      and randomly distributed nanofibers formed a 3D microstructure with relatively
      large pore sizes and high porosity. Biocompatibility analysis revealed that bone
      marrow-derived mesenchymal stem cells exhibited a higher proliferation rate when
      cultured on the NRS compared with the other scaffolds. The mechanical testing
      results indicated that the tensile properties of the NRS were reinforced in the
      direction parallel to the nanoyarns and satisfied the mechanical requirements for
      tendon repair. In addition, cell infiltration was significantly enhanced on the
      NRS. In conclusion, with its improved porosity and appropriate mechanical
      properties, the developed NRS shows promise for tendon tissue engineering
      applications. 

PMID- 25064478
TI  - A novel label-free electrochemiluminescence aptasensor based on layered
      flowerlike molybdenum sulfide-graphene nanocomposites as matrix.
AB  - A label-free and ultrasensitive electrochemiluminescence (ECL) aptasensor was
      constructed for the detection of thrombin. Molybdenum sulfide-graphene
      nanocomposites with good conductivity and large surface area were immobilized on
      glassy carbon electrode (GCE), and then Nafion was fixed to chemosorb the
      Ru(bpy)3(2+) used as luminescence agent. Subsequently, gold nanoparticles (AuNPs)
      were modified on the electrode to immobilize the thiol-modified thrombin aptamer
      for fabrication of the thrombin aptasensor. The proposed ECL aptasensor produced
      the ultrasensitive detection of thrombin with a low detection limit of 3.6*10(
      15)M (S/N=3) and over a wide target concentration range from 1.0*10(-14) to
      5.0*10(-9)M. The aptasensor has been successfully applied in the determination of
      thrombin in human plasma samples of both traumatic and non-traumatic injury
      patients, indicating its promise in biochemical analysis. The recoveries of
      thrombin in human plasma samples are between 88.6% and 105.0%, and the RSD values
      are no more than 3.7%. The results demonstrate that this aptasensor has excellent
      sensitivity, selectivity and stability. 

PMID- 25064477
TI  - Biofunctionalization of gelatin microcarrier with oxidized hyaluronic acid for
      corneal keratocyte cultivation.
AB  - Development of microcarriers as alternative architecture models to traditional
      three-dimensional porous scaffolds can potentially eliminate the concern of
      extensive geographic necrosis during keratocyte cultivation. For the first time,
      this work was performed to evaluate the in vitro expansion of rabbit corneal
      keratocytes (RCKs) on the gelatin microcarrier (GMC) modified with hyaluronic
      acid (HA). In order to confirm the successful synthesis, the oxidized HA (oHA)
      samples following treatment of HA with sodium periodate were investigated by
      chemical characterization, including Fourier transform infrared and nuclear
      magnetic resonance spectroscopy. Biofunctionalization of GMC with oHA was then
      achieved by the formation of aldimine linkage between free amino groups in
      protein and aldehyde groups in oxidized polysaccharide. The grafting yield of oHA
      onto GMC determined by alcian blue staining assay was 26.9+/-0.1%. Tissue culture
      polystyrene (TCPS) plates and the microcarriers from either the GMC or GMC-oHA
      group were used for suspension culture of RCKs. Results of WST-1 assays, scanning
      electron microscopy, extracellular matrix production assays, and quantitative
      real-time reverse transcription polymerase chain reaction and Western blot
      analysis showed that among all the groups studied, the GMC-oHA samples could most
      effectively support a large scale growth of RCKs while enhancing their total
      collagen and glycosaminoglycan contents (i.e., indicative of biosynthetic
      capacity) and keratocan and ALDH1 gene and protein expressions (i.e., indicative
      of cell phenotype and function). It is concluded that the aforementioned
      keratocyte behaviors are found to be strongly dependent on the type of culture
      substrate (i.e., TCPS plate versus biopolymer microcarrier) and on the
      biomaterial functionalization (i.e., modification of gelatin with oHA). 

PMID- 25064479
TI  - Air-ozonolysis to generate contact active antimicrobial surfaces: activation of
      polyethylene and polystyrene followed by covalent graft of quaternary ammonium
      salts.
AB  - Air-ozonolysis was revealed as an accessible and effective approach for surface
      activation and further functionalization of hydrocarbon polymers. Antimicrobial
      contact active polyethylene (PE) and polystyrene (PS) were designed by generation
      on their surfaces OH-functional groups and covalent graft of dimethyloctadecyl [3
      (trimethoxysilyl) propyl] ammonium chloride (C18-TSA) quaternary ammonium salt.
      The shortened analog, trimethyl [3-(trimethoxysilyl) propyl] ammonium chloride
      (C1-TSA), was also covalently attached to the activated PE and PS surfaces. X-ray
      photoelectron spectroscopy (XPS) and FTIR confirmed the surface modifications.
      Scanning electron (SEM) and confocal microscopy were utilized to monitor surface
      morphology and bacteria interactions. The antimicrobial effect of the C18-TSA
      grafted polymer surfaces was demonstrated on Gram-negative and Gram-positive
      bacteria species including human pathogen, Salmonella enterica. The shorter C1
      TSA grafted polymers did not demonstrate bactericidal activity, suggesting the
      critical role of the alkyl chain length. The described strategy may establish a
      new general and safe platform for future development and application of contact
      active antimicrobial polymers. 

PMID- 25064480
TI  - Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.
AB  - A simple and stable curcumin-ceramic combined formulation was developed with an
      aim to improve curcumin stability and release profile in the presence of reactive
      ceramic particles for potential dental and orthopedic applications. For that,
      curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur)
      complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water
      soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at
      10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed
      that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies
      revealed that, divalent Ba(2+) interacted predominantly through di-phenolic
      groups of curcumin to form an end-to-end complex resulted in supramolecular
      multimer. The overall crystallinity of the BaCur was lower than curcumin as per
      XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as
      per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+)
      complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm
      was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon
      loading into pluronic micelles the size was remaining in similar order of
      magnitude as per DLS and AFM studies. Stability of the curcumin was improved
      greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy.
      Loading of the supramloecular nanoparticles into pluronic micelles had further
      improved the stability of curcumin to approx. 70% in water. These BaCur
      supramolecule nanoparticles can be considered as a new class of prodrugs with
      improved solubility and stability. Subsequently, ceramic nanoparticles with
      varying chemical composition were prepared for changing the material surface
      reactivity in terms of the increase in, degradability, surface pH and protein
      adsorption. Further, these ceramic particles were combined with curcumin prodrug
      formulations and optimized the curcumin release properties in the combined
      formulations. Our proof concept study shows that, the conversion of curcumin to a
      metal-organic supramolecular prodrug improved the solubility, stability and
      release profile of curcumin. The prodrug approach with the micellisation strategy
      appears to be more appropriate to deliver intact curcumin in the presence of
      ceramic particles of varying surface reactivity. 

PMID- 25064481
TI  - Prevention of desiccation induced postsurgical adhesion by thermosensitive
      micelles.
AB  - Tissue desiccation is a common cause of postsurgical peritoneal adhesion, which
      leads a variety of adverse consequences in clinic. Until now, many approaches
      have been advocated to prevent postsurgical adhesions, but the therapeutic
      effects were not very encouraging. In this work, biodegradable and
      thermosensitive poly(E-caprolactone)-poly(ethylene glycol)-poly(E-caprolactone)
      (PCL-PEG-PCL) micelles were prepared and assigned for anti-adhesion studies. The
      micelles were a free flowing sol at low temperature, but instantly inverted into
      a non-flowing gel at physiological temperature, which could serve as a potential
      candidate as anti-adhesion barrier. A novel cecum desiccation rat model was
      established and used for anti-adhesion studies. The micelles were sol state
      before use, which could cover the injured cecum unrestrictedly, and then formed
      gel in body temperature and adhered to the injured sites. All the rats in the
      control group developed adhesions with score 5 or 4, whereas none in the micelle
      treated group developed adhesions with score 5 or 4 (P<0.001, Mann-Whitney U
      test). Histopathological assessment also confirmed that the micelles exhibited
      excellent anti-adhesion effects on desiccation-induced peritoneal adhesion.
      Adhesiveness and degradation behavior of the micelles suggested that the micelles
      could adhere to the injured cecum and prevent adhesion in the critical time of
      healing process. The results indicated that the thermosensitive micelles could
      serve as an effective anti-adhesion barrier. 

PMID- 25064482
TI  - Influence of micropattern width on differentiation of human mesenchymal stem
      cells to vascular smooth muscle cells.
AB  - In recent years, various approaches have been taken to generate functional muscle
      tissue by tissue engineering. However, in vitro methods to generate smooth muscle
      with physiologically aligned structure remains limited. In order to mimic the in
      vivo highly organized structure of smooth muscle cells, we used micropatterning
      technology for engineering parallel aligned cells. In this study, a gradient
      micropattern of different width of cell-adhesive polystyrene stripes (5, 10, 20,
      40, 60, 80, 100, 200, 400, 600, 800 and 1000MUm) was prepared and the effects of
      micropattern width on human mesenchymal stem cells (hMSCs) orientation,
      morphology and smooth muscle cell differentiation were investigated. The width of
      micropattern stripes showed obvious effect on cell orientation, morphology and
      smooth muscle cell differentiation. The cells showed higher degree of orientation
      when the micropattern stripes became narrower. Higher expression of calponin and
      smooth muscle actin was observed among the narrow micropatterns ranging from
      200MUm to 20MUm, compared to the non-patterned area and wide micropattern areas
      which showed similar levels of expression. 

PMID- 25064483
TI  - Semi-analytical solution for the in-vitro sedimentation, diffusion and dosimetry
      model: surveying the impact of the Peclet number.
AB  - Reducing size of the particles to the nanoscale range gives them new
      physicochemical properties. Several experiments have shown cytotoxic effects for
      different kinds of engineered nanoparticles (ENP). In-vitro cell culture assays
      are widely utilized by researchers to evaluate cytotoxic effects of the ENPs. The
      present paper deals with the "In vitro Sedimentation, Diffusion and Dosimetry
      (ISDD)" model. This mathematical model uses an advection-diffusion equation with
      specific assumptions and coefficients to estimate the dose of the particles
      delivered to the cells monolayer in the culture medium. In the present work,
      utilizing the generalized integral transform technique (GITT), a semi-analytical
      solution is developed for the ISDD model. The parameters affecting the ISDD
      predictions are integrated into two dimensionless numbers, Pe and tau. The Pe
      number shows the ratio of the convective to the diffusive mass transport rates
      and tau is a dimensionless time parameter. The quality of the results for an
      extensive range of Pe and tau numbers is surveyed through application of the
      developed formula to two series of test cases. A comparison of the results with
      those obtained from numerical methods shows deviations in the numerical results
      at high Pe numbers. Applying the developed formula, ISDD predictions for a wide
      practical range of Pe and tau numbers are calculated and plotted in two- and
      three-dimensional plots. The curves and formula obtained in this study facilitate
      the achievement of ISDD predictions with higher accuracies and capabilities for
      verification of the results. 

PMID- 25064484
TI  - Cyclic RGD-modified chitosan/graphene oxide polymers for drug delivery and
      cellular imaging.
AB  - Polymers based on cyclic RGD-modified chitosan/graphene oxide are investigated in
      this paper as an innovative type of drug delivery system for hepatocellular
      carcinoma-targeted therapy and imaging. The system was prepared using a simple
      noncovalent method by coating drug-loaded graphene oxide (GO) with cyclic RGD
      modified chitosan (RC). The results show that an efficient loading of doxorubicin
      (DOX) on GO (1.00mg/mg) was obtained. The system exhibits a pH-responsive
      behavior because of the hydrogen bonding interaction between GO and RC, and may
      be very stable under physiological conditions but with release at a lower pH
      (tumor environment). In addition, cellular uptake and proliferation studies using
      hepatoma cells (Bel-7402, SMMC-7721, HepG2) indicated that the cRGD-modified
      chitosan/graphene oxide polymer could recognize hepatoma cells and promote drug
      uptake by the cells, especially for cells overexpressing integrins. Together,
      these results demonstrate that the RC/GO polymers provide a multifunctional drug
      delivery system with the ability to target hepatocarcinoma cells, and are pH
      responsive and can be efficiently loaded with a number of therapeutic agents for
      biomedical applications. 

PMID- 25064485
TI  - Ecotoxicity and environmental risk assessment of pharmaceuticals and personal
      care products in aquatic environments and wastewater treatment plants.
AB  - A wide range of pharmaceuticals and personal care products (PPCPs) are present in
      the environment, and many of their adverse effects are unknown. The environmental
      risk assessment of 26 PPCPs of relevant consumption and occurrence in the aquatic
      environment in Spain was accomplished in this research. Based on the ecotoxicity
      values obtained by bioluminescence and respirometry assays and by predictions
      using the US EPA ecological structure-activity relationship (ECOSARTM), the
      compounds were classified following the Globally Harmonized System of
      Classification and Labelling of Chemicals. According to the criteria of the
      European Medicines Agency, the real risk of impact of these compounds in
      wastewater treatment plants (WWTPs) and in the aquatic environment was predicted.
      In at least two ecotoxicity tests, 65.4 % of the PPCPs under study showed high
      toxicity or were harmful to aquatic organisms. The global order of the species'
      sensitivity to the PPCPs considered was as follows: Vibrio fischeri (5 min) >
      Vibrio fischeri (15 min) > algae > crustaceans > fish > biomass of WWTP.
      Acetaminophen, ciprofloxacin, clarithromycin, clofibrate, ibuprofen, omeprazole,
      triclosan, parabens and 1,4-benzoquinone showed some type of risk for the aquatic
      environments and/or for the activated sludge of WWTPs. Development of acute and
      chronic ecotoxicity data, the determination of predicted and measured
      environmental concentrations of PPCPs, the inclusion of metabolites and
      transformation products and the evaluation of mixtures of these compounds will
      allow further improvements of the results of the ERAs and, finally, to
      efficiently identify the compounds that could affect the environment.

PMID- 25064486
TI  - Mechanistic modeling of vacuum UV advanced oxidation process in an annular
      photoreactor.
AB  - A novel mechanistic model that describes the vacuum UV advanced oxidation process
      in an annular photoreactor initiated by 172 nm and 185 nm (in combination with
      253.7 nm, with and without exogenous H2O2) is presented in this paper. The model
      was developed from first principles by incorporating the vacuum UV-AOP kinetics
      into the theoretical framework of in-series continuous flow stirred tank
      reactors. After conducting a sensitivity analysis, model predictions were
      compared against experiments conducted under a variety of conditions: (a) photo
      induced formation of hydrogen peroxide by water photolysis at 172 nm (for both
      air- and oxygen-saturated conditions); (b) photo-induced formation of hydrogen
      peroxide by water photolysis at 185 + 253.7 nm (in the presence of formic acid,
      with and without the initial addition of hydrogen peroxide); (c) direct
      photolysis of hydrogen peroxide by 253.7 nm; (d) degradation of formic acid by
      185 + 253.7 nm (with and without initial addition of hydrogen peroxide); and (e)
      degradation of formic acid by 253.7 nm (with the addition of exogenous hydrogen
      peroxide). In all cases, the model was able to accurately predict the time
      dependent profiles of hydrogen peroxide and formic acid concentrations. Two newly
      recognized aspects associated with water photolysis were identified through the
      use of the validated model. Firstly, unlike the 185 nm and 253.7 nm cases, water
      photolysis by the 172 nm wavelength revealed a depth of photoactive water layer
      an order of magnitude greater (~230-390 MUm, depending on the specific operating
      conditions) than the 1-log photon penetration layer (~18 MUm). To further
      investigate this potentially very important finding, a computational fluid
      dynamics model was set up to assess the role of transport mechanisms and species
      distributions within the photoreactor annulus. The model confirmed that short
      lived hydroxyl radicals were present at a radial distance far beyond the ~18 MUm
      photon penetration layer. Secondly, kinetic simulations showed that the higher
      penetration depth of hydroxyl radicals was not caused by diffusive or convective
      transport phenomena but rather the effect of non-linear behavior of the complex
      reaction kinetics involved in the process. 

PMID- 25064487
TI  - Feasibility and acceptability of hand massage therapy for pain management of
      postoperative cardiac surgery patients in the intensive care unit.
AB  - OBJECTIVE: The purpose was to evaluate the acceptability and feasibility of hand
      massage therapy in the intensive care unit (ICU). BACKGROUND: Clinical guidelines
      suggest the use of non-pharmacological interventions for pain management in ICU
      adults. The results presented are secondary to a pilot RCT evaluating the
      preliminary effectiveness of hand massage on pain after cardiac surgery. METHODS:
      A qualitative descriptive design was used. Acceptability was evaluated using
      individual interviews with participants in both groups i.e., experimental and
      control (n = 40). Feasibility was examined using field notes and video
      recordings. RESULTS: While participants receiving the massage perceived it as
      appropriate, the control group suggested different dosages of the treatment and
      body areas targeted. Results also suggest that barriers (e.g. noise, numerous
      clinical activities) need to be overcome. CONCLUSIONS: Increasing staff
      acceptance, reducing the rest period, involving families, and repeating the
      treatment are avenues to consider. Building evidence for non-pharmacological pain
      management in the critical care setting is necessary.

PMID- 25064488
TI  - Rgn gene is required for gut cell homeostasis after ingestion of sodium dodecyl
      sulfate in Drosophila.
AB  - Resistance and resilience constitute the two complementary aspects of epithelial
      host defenses in Drosophila. Epithelial cell homeostasis is necessary for the
      recovery of damages caused by stress or infections. However, the genes
      responsible for gut epithelial homeostasis remain poorly understood. Here, we
      show that rgn(G4035) mutant flies have higher mortality than wild-type flies
      after ingestion of sodium dodecyl sulfate (SDS). Excessive melanization and
      increased necrotic cells in the gut contribute to the reduced survival of
      rgn(G4035) mutant flies following SDS ingestion. rgn mutant flies have a defect
      in the replenishment of intestinal stem cells (ISCs) following gut damage. The
      antimicrobial peptide (AMP) expression is affected in rgn(G4035) mutant fly guts.
      Together, our study provides evidence that rgn gene is essential for gut cell
      homeostasis following damage in Drosophila.

PMID- 25064489
TI  - Genetic predisposition to obesity and risk of subclinical atherosclerosis.
AB  - Obesity has been associated with increased common carotid artery (CCA) intima
      media thickness (IMT), a measure of subclinical atherosclerosis. We assessed the
      association between genetic predisposition to obesity and CCA IMT. The study
      included 428 young Chinese adults with CCA IMT measured using a high-resolution B
      mode tomographic ultrasound system. We created a genetic risk score (GRS) by
      summing the risk alleles of 6 obesity-associated genetic variants confirmed in
      our previous analyses. The GRS was significantly associated with greater CCA IMT
      (p<0.001) after adjustment for age and gender. Per 2 alleles of the GRS was
      related to 0.023 mm increment in IMT. The association was attenuated by one half
      with additional adjustment for obesity status, but remained significant
      (p=0.009). In addition, we found that blood pressure significantly modified the
      association between the GRS and CCA IMT (p for interaction=0.001). The
      associations between the GRS and CCA IMT were stronger in participants with
      systolic blood pressure (SBP) >=120 mmHg and/or diastolic blood pressure (DBP)
      >=80 mmHg (per 2 allele increment of the GRS relating to 0.028 mm greater CCA
      IMT, p for trend<0.001) than those with SBP<120 mmHg and DBP<80 mmHg (per 2
      allele increment of the GRS relating to 0.001 smaller CCA IMT, p for
      trend=0.930). Our data provides suggestive evidence supporting the potential
      causal relation between obesity and development of subclinical atherosclerosis.
      Elevated blood pressure might amplify the adverse effect of obesity on
      cardiovascular risk.

PMID- 25064490
TI  - Characterization and identification of the integrin family in silkworm, Bombyx
      mori.
AB  - As an important economic insect, Bombyx mori is also a useful model organism for
      lepidopteran insect. Integrins are evolutionarily conserved from sponges to
      humans, and play vital roles in many physiological and pathological processes. To
      explore their diverse functions of integrins in insect, eleven integrins
      including six alpha and five beta subunits were cloned and characterized from
      silkworm. Our results showed that integrins from silkworm own more family members
      compared to other invertebrates. Among those alpha subunits, integrins alpha1,
      alpha2, and the other four subunits belong to PS1, PS2, and PS3 groups,
      respectively. The beta subunits mainly gather in the insect betanu group except
      the beta1 subunit which belongs to the insect beta group. Expression profiles
      demonstrated that the integrins exhibited distinct patterns, but were mainly
      expressed in hemocytes. alpha1 and beta2 subunits are the predominant ones either
      in the embryogenesis or larva stages. Interestingly, integrins were significantly
      up-regulated after stimulated by 20-hydroxyecdysone (20-E) in vivo. These results
      indicate that integrins perform diverse functions in hemocytes of silkworm.
      Overall, our results provide a new insight into the functional and evolutionary
      features of integrins.

PMID- 25064491
TI  - Point-of-care ultrasound: seeing the future.
AB  - Practitioners other than radiologists and certified sonographers are increasingly
      using ultrasound at the bedside to facilitate immediate patient management from
      both procedural and diagnostic standpoints. This editorial provides a brief
      overview of the use of point-of-care ultrasound in clinical practice, its
      potential to improve patient care, and some of the unanswered questions
      surrounding issues of training, scope of practice, and quality assurance. 

PMID- 25064492
TI  - Serum vitamin D is low and inversely associated with LDL cholesterol in the Kazak
      ethnic population: a cross-sectional study.
AB  - BACKGROUND: Accumulating evidence suggests that low concentrations of serum
      25(OH)D is coupled with increased risks of hypertension, obesity, and
      cardiovascular disease. However, this relationship has not been established in
      populations with very low levels of 25(OH)D. Therefore, the aim of our study was
      to clarify the associations between 25(OH)D and blood pressure, obesity, sex, and
      lipid profiles in the Kazak ethnic population, who have an extremely low level of
      25(OH)D. MATERIAL/METHODS: A multistage-cluster sampling survey was carried out
      for residents with Kazak ethnicity in Xinjiang, China. Anthropometric
      measurements of each participant were taken and the concentrations of 25(OH)D,
      calcium, alkaline phosphatase, and lipid profiles were measured. Individuals were
      classified into different groups in terms of vitamin D status, degree of
      adiposity, presence of hypertension, and other comorbidities. RESULTS: The madian
      concentration of 25(OH)D was 16.2 (11.8-20.5) ng/mL and the prevalence of vitamin
      D deficiency was 72.4% in this Kazak population (n=928, 59.0% women). Females had
      a lower 25(OH)D concentration than males - 14.6 (10.5-19.4) ng/mL vs. 17.7 (14.8
      22.5) ng/mL, P<0.001. The subjects were classified into 3 groups according to
      their vitamin D status. There were significant differences in BMI (P=0.046),
      waist circumference (P=0.037), hip circumference (P=0.003), systolic BP
      (P=0.035), and LDL cholesterol (P=0.008) among the groups after adjustment for
      sex and age. On the other hand, there was no significant difference in vitamin D
      levels between groups with or without hypertension (P=0.586), and groups with or
      without obesity (P=0.639). A multifactor-regression analysis revealed that every
      increment of 1mg/dL in LDL cholesterol was associated with a 1.0 ng/mL decline in
      serum 25(OH)D. CONCLUSIONS: The insufficiency of vitamin D is highly prevalent in
      Kazaks. Sex, LDL cholesterol, and hip circumference are 3 variables strongly
      associated with serum 25(OH)D concentration. In a population with low levels of
      25(OH)D, the negative relationship between obesity and serum 25(OH)D, a common
      finding from most previous studies, could not be established.

PMID- 25064494
TI  - Abstracts of the 20th International Symposium on Regulatory Peptides
      (REGPEP2014), September 7-10, 2014, Kyoto, Japan.

PMID- 25064493
TI  - Indoleamine 2,3-dioxygenase increases p53 levels in alloreactive human T cells,
      and both indoleamine 2,3-dioxygenase and p53 suppress glucose uptake, glycolysis
      and proliferation.
AB  - Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity by inhibiting T
      cell proliferation and altering glucose metabolism. The tumor suppressor p53 also
      alters these cellular processes with similar results. The effect of IDO on p53
      and on glucose metabolism was evaluated in alloreactive T cells. Mixed-lymphocyte
      reactions (MLRs) were performed in the presence or not of the IDO inhibitor, 1-dl
      methyl-tryptophan (1-MT) and/or the p53 inhibitor, pifithrin-alpha (PFT). Cell
      proliferation, glucose consumption and lactate production were assessed. 1-MT
      increased cell proliferation, glucose influx and lactate production, whereas PFT
      enhanced cell proliferation and glucose influx, leaving lactate production
      unaffected. In MLR-derived T cells, protein analysis revealed that IDO activated
      general control non-derepressible 2 kinase and induced p53, p-p53 (p53
      phosphorylated at serine 15) and p21. In addition, both IDO and p53 decreased
      glucose transporter 1 and TP53-induced glycolysis and apoptosis regulator and
      increased synthesis of cytochrome c oxidase 2. IDO also reduced lactate
      dehydrogenase-A and glutaminase 2 levels, whereas p53 left them unaffected.
      Neither 1-MT nor PFT affected glucose-6-phosphate dehydrogenase. In conclusion,
      in alloreactive T cells, IDO increases p53 levels, and both IDO and p53 inhibit
      cell proliferation, glucose consumption and glycolysis. Lactate production and
      glutaminolysis are also suppressed by IDO, but not by p53. 

PMID- 25064495
TI  - Distinct amygdalar AMPAergic/GABAergic mechanisms promote anxiolitic-like effects
      in an unpredictable stress model of the hamster.
AB  - Studies have pointed to both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid receptor (AMPAR) antagonists and GABA(A) receptor (GABA(A)R) agonists as
      potent antistress agents. In this work, separate subchronic injections of the
      AMPAR antagonist, 6-ciano-7-nitroquinoxaline-2,3-dione (CNQX), and alpha1
      GABA(A)R subunit agonist (Zol) within the central amygdala nucleus modified the
      elevated plus maze performances of hamsters exposed randomly to one of the
      following stressful conditions: food/water deprivation, forced swimming test, and
      permanence in cold room. Indeed, stressed hamsters treated with CNQX or Zol
      displayed a very great (p < 0.001) increase of entrance plus a moderate (p <
      0.05) time spent into open arms, respectively. At the cellular level, Zol-treated
      animals supplied a moderately evident argyrophilic reaction (indicative of
      neurodegeneration) in the hippocampus while it was absent in the hypothalamus.
      Interestingly, this reaction was significantly reduced by CNQX supporting its
      preferential protective role. Furthermore, both agents were responsible for a
      mixed expression pattern of GluR1 and GluR2 mRNA levels in which Zol overall
      upregulated GluR1 mRNAs, while they were downregulated by CNQX in the hippocampal
      oriens-pyramidalis layer and in layer III of the cerebral cortex. These findings
      support the amygdalar AMPAergic protective response against anxiety states in
      chronically stressed hamsters, which may constitute useful therapeutic strategies
      for panic-related mood disorders.

PMID- 25064496
TI  - Effects of the anti-multiple sclerosis immunomodulator laquinimod on anxiety and
      depression in rodent behavioral models.
AB  - Laquinimod is a novel oral immunomodulatory drug for the treatment of multiple
      sclerosis (MS). Considering the frequent co-morbidity of MS with anxiety and
      depression, we sought to assess the antidepressant and anxiolytic effects of
      laquinimod in mouse models. Laquinimod (0.5-25 mg/kg), fluoxetine (10 mg/kg) or
      vehicle were administered for 4-14 days to adult Balb/c mice, followed by
      behavioral tests and brain BDNF analysis. Following a 4-day administration of
      laquinimod (5 and 25 mg/kg), an increase in motivated behavior was observed in
      the forced swim test (p < 0.01 vs. controls). In the open field test, laquinimod
      (0.5-5 mg/kg), but not fluoxetine, significantly increased motility (p < 0.05),
      whereas both decreased anxiety behavior (p < 0.01), evident only for laquinimod
      (5 mg/kg) in the elevated plus maze (p < 0.05). Following 7 days of
      administration, both drugs decreased anxiety behavior in the elevated plus maze
      and marble burying tests (p < 0.001 and p < 0.02, respectively). After 14 days,
      only laquinimod (5 mg/kg) demonstrated anxiolytic efficacy in the open field test
      (p < 0.05), with evidence of increased BDNF in response to 5-25 mg/kg in the
      hippocampus, but not frontal cortex (p < 0.05). In conclusion, laquinimod may
      possess anxiolytic and antidepressant effects, possibly associated with
      hippocampal BDNF increase, offering promise for MS patients suffering from
      psychiatric co-morbidity.

PMID- 25064497
TI  - Clinical and histological findings associated with autoantibodies detected by RNA
      immunoprecipitation in inflammatory myopathies.
AB  - Of 207 adult patients with idiopathic inflammatory myopathies, detection of
      autoantibodies by RNA immunoprecipitation showed that 99 patients (48%) were
      antibody-positive. We divided these 99 into five subgroups: anti-signal
      recognition particle (SRP), anti-aminoacyl transfer RNA synthetase, anti-Ku, anti
      U1RNP, and anti-SSA/B. Younger age at onset, severe weakness, muscle atrophy,
      elevated creatine kinase, and necrosis in muscle fibers without inflammatory cell
      infiltration were found significantly more frequently among the patients with
      anti-SRP antibodies (n=41) compared to the antibody-negative patients (n=108).
      Autoantibody detection by RNA immunoprecipitation can provide useful information
      associated with clinical and histological findings. 

PMID- 25064498
TI  - Disease modifying drugs modulate endogenous secretory receptor for advanced
      glycation end-products, a new biomarker of clinical relapse in multiple
      sclerosis.
AB  - OBJECTIVES: This study is one in a series measuring RAGE axis (receptor for
      advanced glycation end products, its isoforms, and ligands) and its potential as
      a biomarker in multiple sclerosis (MS). We evaluated serum levels of the
      endogenous secretory RAGE (esRAGE) in MS patients and assessed the relationship
      between esRAGE levels and the use of disease modifying drugs (DMDs), and between
      esRAGE levels and indicators of MS disease severity. METHOD: esRAGE serum levels
      were compared between 98 MS patients and 34 healthy controls (HCs) using ELISA.
      RESULTS: esRAGE serum levels were similar between MS and HCs. DMD-treated
      patients had higher esRAGE serum levels than DMD-naive patients (395.7+/
      38.6pg/ml vs. 299.2+/-20.1pg/ml, P=0.02). DMD-naive, primary progressive (PP)
      patients had higher esRAGE serum levels, than relapsing remitting (RR) (P=0.02)
      and secondary progressive (SP) (P=0.04) patients; RRMS patients in clinical
      relapse had lower esRAGE serum levels than clinically stable patients (219.7+/
      30.0pg/ml vs. 338.2+/-31.6pg/ml, P=0.02). In a univariate regression analysis of
      DMD-naive MS patients, esRAGE serum levels inversely correlated with the rate of
      clinical relapse (r=-0.44, P=0.006), MS severity scale (MSSS) (r=-0.32, P=0.03),
      and expanded disability status scale (EDSS) (r=-0.251, P=0.07). CONCLUSION:
      esRAGE serum levels are modulated by DMDs. The serum levels may be a useful
      biomarker of MS clinical relapse.

PMID- 25064499
TI  - The synthesis and mercury-recognizing skill of two emission "turn-on" rhodamine
      derivatives excited by rare earth up-conversion lattice.
AB  - The present paper focused on the synthesis and Hg(II)-sensing behavior of two
      rhodamine derived probes. Up-conversion NaYF4 nanocrystals were constructed and
      applied as the excitation host so that those probes could be lightened by the 980
      nm excited up-conversion emission, aiming at better probe photostability. The
      efficient energy transfer between the up-conversion host and the probes was
      analyzed and confirmed by spectral analysis and emission decay lifetime
      comparison. The probes followed a simple complexation stoichiometry of 1:1 with
      Hg(II) ions. Then two sensing composite systems containing the up-conversion host
      and the probes were established. Their sensing performance, including spectral
      response, Stern-Volmer plots, emission stability and selectivity, was explored in
      detail. It was found that the probe emission linearly increased with increasing
      Hg(II) ions while was immune to other common metal ions, showing emission "turn
      on" effect towards Hg(II) ions with good selectivity.

PMID- 25064500
TI  - Spectroscopic characterization, antioxidant and antitumour studies of novel bromo
      substituted thiosemicarbazone and its copper(II), nickel(II) and palladium(II)
      complexes.
AB  - A new, slightly distorted octahedral complex of copper(II), square planar
      complexes of nickel(II) and palladium(II) with 2,4'-dibromoacetophenone
      thiosemicarbazone (DBAPTSC) are synthesized. The ligand and the complexes are
      characterized by FT-IR, FT-Raman, powder X-ray diffraction studies. The IR and
      Raman data are correlated for the presence of the functional groups which
      specifically helped in the confirmation of the compounds. In addition, the free
      ligand is unambiguously characterized by (1)H and (13)C NMR spectroscopy while
      the copper(II) complex is characterized by electron paramagnetic resonance
      spectroscopy (EPR). The g values for the same are found to be 2.246 (g1), 2.012
      (g2) and 2.005 (g3) which suggested rhombic distortions. The HOMO-LUMO band gap
      calculations for these compounds are found to be in between 0.5 and 4.0 eV and
      these compounds are identified as semiconducting materials. The synthesized
      ligand and its copper(II), nickel(II) and palladium(II) complexes are subjected
      to antitumour activity against the HepG2 human hepatoblastoma cell lines. Among
      all the compounds, nickel(II) complex is found to exert better antitumour
      activity with 57.6% of cytotoxicity.

PMID- 25064501
TI  - Diagnosis of colorectal cancer by near-infrared optical fiber spectroscopy and
      random forest.
AB  - Near-infrared (NIR) spectroscopy has such advantages as being noninvasive, fast,
      relatively inexpensive, and no risk of ionizing radiation. Differences in the NIR
      signals can reflect many physiological changes, which are in turn associated with
      such factors as vascularization, cellularity, oxygen consumption, or remodeling.
      NIR spectral differences between colorectal cancer and healthy tissues were
      investigated. A Fourier transform NIR spectroscopy instrument equipped with a
      fiber-optic probe was used to mimic in situ clinical measurements. A total of 186
      spectra were collected and then underwent the preprocessing of standard normalize
      variate (SNV) for removing unwanted background variances. All the specimen and
      spots used for spectral collection were confirmed staining and examination by an
      experienced pathologist so as to ensure the representative of the pathology.
      Principal component analysis (PCA) was used to uncover the possible clustering.
      Several methods including random forest (RF), partial least squares-discriminant
      analysis (PLSDA), K-nearest neighbor and classification and regression tree
      (CART) were used to extract spectral features and to construct the diagnostic
      models. By comparison, it reveals that, even if no obvious difference of
      misclassified ratio (MCR) was observed between these models, RF is preferable
      since it is quicker, more convenient and insensitive to over-fitting. The results
      indicate that NIR spectroscopy coupled with RF model can serve as a potential
      tool for discriminating the colorectal cancer tissues from normal ones. 

PMID- 25064502
TI  - A Raman spectroscopic study of the arsenate mineral chenevixite
      Cu2Fe2(3+)(AsO4)2(OH)4?H2O.
AB  - We have studied the mineral chenevixite from Manto Cuba Mine, San Pedro de
      Cachiyuyo District, Inca de Oro, Chanaral Province, Atacama Region, Chile, using
      a combination of scanning electron microscopy (SEM) with energy dispersive
      spectroscopy (EDX) and vibrational spectroscopy. Qualitative chemical analysis
      shows a homogeneous composition, with predominance of As, Fe, Al, Cu, Fe and Cu.
      Minor amounts of Si were also observed. Raman spectroscopy complimented with
      infrared spectroscopy has been used to assess the molecular structure of the
      arsenate minerals chenevixite. Characteristic Raman and infrared bands of the
      (AsO4)(3-) stretching and bending vibrations are identified and described. The
      observation of multiple bands in the (AsO4)(3-) bending region offers support for
      the loss of symmetry of the arsenate anion in the structure of chenevixite. Raman
      bands attributable to the OH stretching vibrations of water and hydroxyl units
      were analysed. Estimates of the hydrogen bond distances were made based upon the
      OH stretching wavenumbers. 

PMID- 25064503
TI  - A fluorescence detection of D-penicillamine based on Cu(2+)-induced fluorescence
      quenching system of protein-stabilized gold nanoclusters.
AB  - In this contribution, a luminescent gold nanoclusters which were synthesized by
      bovine serum albumin as novel fluorescent probes were successfully utilized for
      the determination of D-penicillamine for the first time. Cupric ion was employed
      to quench the strong fluorescence of the gold nanoclusters, whereas the addition
      of D-penicillamine caused obvious restoration of fluorescence intensity of the
      Cu(2+)-gold nanoclusters system. Under optimum conditions, the increment in
      fluorescence intensity of Cu(2+)-gold nanoclusters system caused by D
      penicillamine was linearly proportional to the concentration of D-penicillamine
      in the range of 2.0*10(-5)-2.39*10(-4) M. The detection limit for D-penicillamine
      was 5.4*10(-6) M. With the off-on fluorescence signal at 650 nm approaching the
      near-infrared region, the present sensor for D-penicillamine detection had high
      sensitivity and low spectral interference. Furthermore, the novel gold
      nanoclusters-based fluorescent sensor has been applied to the determination of D
      penicillamine in real biological samples with satisfactory results.

PMID- 25064504
TI  - Composition and spectra of copper-carotenoid sediments from a pyrite mine stream
      in Spain.
AB  - Mine drainages of La Poderosa (El Campillo, Huelva, Spain), located in the Rio
      Tinto Basin (Iberian Pyrite Belt) generate carotenoid complexes mixed with copper
      sulfates presenting good natural models for the production of carotenoids from
      microorganisms. The environmental conditions of Rio Tinto Basin include important
      environmental stresses to force the microorganisms to accumulate carotenoids.
      Here we show as carotenoid compounds in sediments can be analyzed directly in the
      solid state by Raman and Luminescence spectroscopy techniques to identify solid
      carotenoid, avoiding dissolution and pre-concentration treatments, since the
      hydrous copper-salted paragenesis do not mask the Raman emission of carotenoids.
      Raman spectra recorded from one of these specimens' exhibit major features at
      approximately 1006, 1154, and 1520 cm(-1). The bands at 1520 cm(-1) and 1154 cm(
      1) can be assigned to in-phase C=C (gamma(-1)) and C-C stretching (gamma(-2))
      vibrations of the polyene chain in carotenoids. The in-plane rocking deformations
      of CH3 groups linked to this chain coupled with C-C bonds are observed in the
      1006 cm(-1) region. X-irradiation pretreatments enhance the cathodoluminescence
      spectra emission of carotenoids enough to distinguish organic compounds including
      hydroxyl and carboxyl groups. Carotenoids in copper-sulfates could be used as
      biomarkers and useful proxies for understanding remote mineral formations as well
      as for terrestrial environmental investigations related to mine drainage
      contamination including biological activity and photo-oxidation processes.

PMID- 25064505
TI  - Spectroscopic characterization and biological activity of dihydrazone transition
      metal complexes: crystal structure of 2,3-butanedione bis(isonicotinylhydrazone).
AB  - Metal complexes of the chloride, nitrate and acetate salts of Co(II), Ni(II)
      Cu(II), Zn(II), Cd(II) or Hg(II) with 2,3-butanedione bis(isonicotinylhydrazone)
      [BBINH] have been synthesized and structurally characterized. The crystal of
      BBINH was solved to crystallize as monoclinic system with space group of
      P121/c14. The formulae of the complexes were assigned based on the elemental
      analysis and mass spectra. The formation of BBINH complexes depend on the metal
      anion used. All complexes are nonelectrolytes except for the complexes 2, 3, 4
      are (1:1) and 13 and 14 which are 1:2 electrolytes. BBINH behaves as a neutral
      tetradentate (N2O2) in the chloride complexes of Ni(II), Cu(II), Zn(II), Cd(II)
      and Hg(II). In [Co2(BBINH)(H2O)Cl3]Cl?H2O, BBINH has the same dentate but with
      the two Co(II) ions. In the acetate complexes, [Ni2(BBINH-2H)(H2O)2(OAc)2]?3H2O
      and [Cu2(BBINH-2H)(OAc)2]?5H2O, BBINH acts as a binegative tetradentate with the
      two metal ions. The ligand in the nitrate complexes acts as a neutral bidentate
      via the two hydrazone azomethine C=NHy; the nitrate ions are ionic in the Cd(II)
      and Zn(II) complexes and covalent in the Ni(II) complex. The data are supported
      by NMR ((1)H and (13)C) spectra. The magnetic moments and electronic spectra of
      all complexes provide tetrahedral, square planar and/or octahedral structure. The
      decomposition of the complexes revealed the outer and inner solvents as well as
      the remaining residue based on TGA. The complexes have variable activities
      against some bacteria and fungi. The ligand is inactive against all tested
      organisms. The activity of Cd(II) and Hg(II) may be related to the geometry of
      the complexes.

PMID- 25064506
TI  - Synthesis, structure and antimicrobial evaluation of new 3,3a,4,5-tetrahydro-2H
      benzo[g]indazol-2-yl-thiazol-4(5H)-ones.
AB  - The reaction of semicarbazide or thiosemicarbazide with 2-arylidene-1-tetralones
      under alkaline condition affords 3,3a,4,5-tetrahydro-2H-benzo[g]indazole-2
      carbo(thio)amides as a mixture of cis and trans diastereoisomers of 3-H and 3a-H.
      The synthesis of new indazolyl-thiazol-4(5H)-ones from the condensation of cis
      isomer and alpha-halo acids is reported. A DFT study along with X-ray single
      crystal data of a representative compound is presented. All the eight newly
      synthesised indazolyl-thiazol-4(5H)-ones were screened for their antibacterial
      and antifungal activities and some compounds have shown promising activities. 

PMID- 25064507
TI  - Synthesis, spectral characterization, molecular modeling and in vitro
      antibacterial activity of complexes designed from OO, NO and NN donor Schiff-base
      ligand [corrected].
AB  - A new chelating agent, N'-(4-methoxybenzylidene)-2-oxo-2
      (phenylamino)acetohydrazide (H2OMPH) and its complexes with Mn(II), Co(II),
      Ni(II), Cu(II), Zn(II), Hg(II) and U(IV)O2(2+) ions have been prepared and
      characterized by conventional techniques. The spectral data indicated that the
      ligand coordinates as neutral bidentate with Cu(II), Mn(II), U(IV)O2(2+) and
      Hg(II), neutral tridentate with Ni(II), mononegative tridentate with Co(II) and
      binegative tetradentate with Zn(II) ions. On basis of magnetic and electronic
      spectral data an octahedral geometry for Mn(II), Co(II) and Ni(II) complexes and
      a square planar geometry for Cu(II) complex have been proposed and confirmed by
      applying geometry optimization and conformational analysis. The protonation
      constants of H2OMPH and the stepwise stability constants of its complexes are
      calculated at 298, 308 and 318 k as well as their thermodynamic parameters. Also,
      the Kinetic parameters (Ea, A, DeltaH(*), DeltaS(*) and DeltaG(*)) were
      determined for each thermal degradation stage of some complexes using Coats
      Redfern and Horowitz-Metzger methods. Moreover, the ligand and some complexes
      were screened for in vitro antibacterial activity against Staphylococcus
      epidermalies (St. epid); Streptococcus pyagenies (Strp. py.) as Gram +ve bacteria
      and Escherichia coli (E. coli); Klebsiella spp. (kleb. spp.) as Gram -ve bacteria
      using inhibition zone diameter.

PMID- 25064508
TI  - Can physical examination predict the intraarticular tear pattern of the anterior
      cruciate ligament?
AB  - PURPOSE: We evaluated the correlation between physical examinations and the tear
      patterns of the anterior cruciate ligament (ACL). MATERIALS AND METHODS: From
      January 2003 to May 2007, we reviewed 201 cases of ACL rupture, diagnosed by MRI.
      Two orthopaedic surgeons (a fellow and a senior surgeon) evaluated the
      instability of the knee under anaesthesia: physical examinations were the
      anterior draw test (AD), Lachman test (LT), and pivot shift test (PT). By
      describing the rupture pattern and the site of the anteromedial (AMB) and
      posterolateral bundle (PLB) during arthroscopic examination, we analysed the
      correlation between the physical examination under anaesthesia and arthroscopic
      findings. RESULTS: In terms of the arthroscopic findings, rupture of the PLB was
      seen in 83 cases (41.3 %), of the AMB in 24 cases (11.9 %), and of both bundles
      in 94 cases (46.8 %). The kappa values for the physical examinations between the
      examiners were 0.963 (AD), 0.92 (LT), and 0.865 (PT). AD and LT above grade 2 did
      not differ significantly according to the pattern of rupture, but a PT above
      grade 2 was significantly different in ruptured PLB versus complete rupture.
      CONCLUSIONS: A PT of more than grade 2 is a reliable physical examination for
      prediction of ruptured PLB or complete rupture.

PMID- 25064509
TI  - Comparing the outcomes between Chopart, Lisfranc and multiple metatarsal shaft
      fractures.
AB  - OBJECTIVES: Complex midfoot injuries could lead to severe functional impairment
      of mobility and quality of daily living. Aim of this study was to compare the
      clinical and functional outcomes of Chopart, Lisfranc fractures and multiple
      metatarsal shaft fractures. DESIGN: Retrospective case series. SETTING: Level one
      trauma center. INTERVENTION: Open or closed reduction and internal fixation with
      screws, K-wires, plates, external fixation or combination of different technics.
      MAIN OUTCOME MEASUREMENTS: The American Orthopaedic Foot and Ankle Society
      (AOFAS) Midfoot Score and the Maryland Foot Score were used to assess pain and
      functional outcome. 3D gait analysis, pedobarographic analysis and radiologic
      examinations were performed. The activity level was measured by a step counting
      accelerometer. All results were compared to an age-matched healthy control group.
      RESULTS: 24 patients with a median age of 44 years (16-72) were included: 12
      patients with multiple metatarsal shaft fractures, 6 patients with Chopart and 6
      patients with Lisfranc fractures. The median follow-up was 2.6 years. The
      pedobarographic analysis reports reduced contact time of the total foot (p =
      0.08), the forefoot (p = 0.008) and the hallux (p = 0.015) for the injured foot.
      A median score of 64 for the SF-36, 64 for the AOFAS Midfoot Score and 73 for the
      Maryland Foot Score indicated a poor restoration of foot function. Multiple
      metatarsal shaft fractures presented a significantly lower walking speed (p =
      0.03) and cadence (p = 0.04). CONCLUSION: The worst results were reported for
      multiple metatarsal shaft fractures on outcome scores, pedobarography, gait
      analysis and activity. Metatarsal serial fractures should not be underestimated
      as well as Chopart and Lisfranc fractures. LEVEL OF EVIDENCE: Level IV.

PMID- 25064510
TI  - Reticulate evolution in the apogamous Dryopteris varia complex (Dryopteridaceae,
      subg. Erythrovariae, sect. Variae) and its related sexual species in Japan.
AB  - Apogamous fern species are often difficult to distinguish from related species
      because of their continuous morphological variations. To clarify the genetic
      relationships among the members of the Dryopteris varia complex, we analyzed the
      nucleotide sequences of the plastid gene rbcL and the nuclear gene PgiC. We also
      analyzed the diploid sexual species D. caudipinna and D. chinensis, which have
      not been included in the complex, but were recently shown to be closely related
      to the complex in a molecular phylogenetic study. The PgiC sequences of the
      diploid sexual species, D. varia, D. saxifraga, D. sp. 'protobissetiana'
      (undescribed diploid sexual species), D. caudipinna, and D. chinensis, were well
      differentiated and hence designated A, B, C, D, and E, respectively. Thus, the
      PgiC constitution of apogamous species in the complex was as follows: D.
      bissetiana, B + C; D. kobayashii, B + C + E); D. pacifica, A + C, A + B + C, or A
      + C + D; D. sacrosancta, A + C + E; and D. saxifragivaria, B + C. These results
      suggest that these apogamous species are formed by hybridizations of species
      including not only the three diploid sexual species of the D. varia complex (A,
      B, and C) but also the two diploid sexual species D. caudipinna (D) and D.
      chinensis (E), which do not belong to the complex.

PMID- 25064511
TI  - Selectivity mechanism of a bacterial homolog of the human drug-peptide
      transporters PepT1 and PepT2.
AB  - Peptide transporters of the PepT family have key roles in the transport of di-
      and tripeptides across membranes as well as in the absorption of orally
      administered drugs in the small intestine. We have determined structures of a
      PepT transporter from Shewanella oneidensis (PepT(So2)) in complex with three
      different peptides. The peptides bind in a large cavity lined by residues that
      are highly conserved in human PepT1 and PepT2. The bound peptides adopt extended
      conformations with their N termini clamped into a conserved polar pocket. A
      positively charged patch allows differential interactions with the C-terminal
      carboxylates of di- and tripeptides. Here we identify three pockets for peptide
      side chain interactions, and our binding studies define differential roles of
      these pockets for the recognition of different subtypes of peptide side chains.

PMID- 25064513
TI  - Chimeric influenza-virus-like particles containing the porcine reproductive and
      respiratory syndrome virus GP5 protein and the influenza virus HA and M1
      proteins.
AB  - Both porcine reproductive and respiratory syndrome and swine influenza are acute,
      highly contagious swine diseases. These diseases pose severe threats for the
      swine industry and cause heavy economic losses worldwide. In this study, we have
      developed a chimeric virus-like particle (VLP) vaccine candidate for porcine
      reproductive and respiratory syndrome virus (PRRSV) and H3N2 influenza virus and
      investigated its immunogenicity in mice. The HA and M1 proteins from the H3N2
      influenza virus and the PRRSV GP5 protein fused to the cytoplasmic and
      transmembrane domains of the NA protein were both incorporated into the chimeric
      VLPs. Analysis of the immune responses showed that the chimeric VLPs elicited
      serum antibodies specific for both PRRSV GP5 and the H3N2 HA protein, and they
      stimulated cellular immune responses compared to the responses to equivalent
      amounts of inactivated viruses. Taken together, the results suggested that the
      chimeric VLP vaccine represents a potential strategy for the development of a
      safe and effective vaccine to control PRRSV and H3N2 influenza virus. 

PMID- 25064514
TI  - Mybs in mouse hair follicle development.
AB  - The Myb transcription factors are involved in essential cellular processes, such
      as cell proliferation, differentiation and cell death. Biological functions
      carried out by specific Myb proteins are distinct. Hair follicles are ectodermal
      derived organs with cycling character of the growth resulting from the presence
      of somatic stem cells. In this study, we followed the expression of the Myb
      proteins in developing hair follicles and in the hair follicle stem cell niche by
      immunofluorescence staining. During hair follicle development, B-Myb was present
      in a few cells located in the area of cell division; c-Myb was abundant
      postanally in dividing cells but also in keratinizing zone. In addition, c-Myb
      was also detected in cells under the hair follicle bulge. These findings indicate
      possible involvement of c-Myb in regulation of activated stem cells leaving the
      niche.

PMID- 25064512
TI  - Structure of the mammalian 80S initiation complex with initiation factor 5B on
      HCV-IRES RNA.
AB  - The universally conserved eukaryotic initiation factor (eIF) 5B, a translational
      GTPase, is essential for canonical translation initiation. It is also required
      for initiation facilitated by the internal ribosomal entry site (IRES) of
      hepatitis C virus (HCV) RNA. eIF5B promotes joining of 60S ribosomal subunits to
      40S ribosomal subunits bound by initiator tRNA (Met-tRNAi(Met)). However, the
      exact molecular mechanism by which eIF5B acts has not been established. Here we
      present cryo-EM reconstructions of the mammalian 80S-HCV-IRES-Met-tRNAi(Met)
      eIF5B-GMPPNP complex. We obtained two substates distinguished by the rotational
      state of the ribosomal subunits and the configuration of initiator tRNA in the
      peptidyl (P) site. Accordingly, a combination of conformational changes in the
      80S ribosome and in initiator tRNA facilitates binding of the Met-tRNAi(Met) to
      the 60S P site and redefines the role of eIF5B as a tRNA-reorientation factor. 

PMID- 25064515
TI  - [Healing of a resistant neurotrophic corneal ulcer using a new matrix therapy
      agent].

PMID- 25064516
TI  - A meta-analysis of minimally invasive versus conventional sternotomy for aortic
      valve replacement.
AB  - Minimally invasive aortic valve replacement (AVR) is increasingly used as an
      alternative to conventional AVR, despite limited randomized evidence available.
      To assess the evidence base, a systematic search identified 50 comparative
      studies with a total of 12,786 patients. A meta-analysis demonstrated that
      minimally invasive AVR is associated with reduced transfusion incidence,
      intensive care stay, hospitalization, and renal failure, and has a mortality rate
      that is comparable to conventional AVR. The evidence quality was mostly very low.
      Given the inadequate statistical power and heterogeneity of available studies,
      prospective randomized trials are needed to assess the benefits and risks of
      minimally invasive AVR approaches. 

PMID- 25064517
TI  - Development of an experimental model of portal vein ligation associated with
      parenchymal transection (ALPPS) in rats.
AB  - BACKGROUND: Liver failure might be a cause of death after major hepatectomies.
      The ALPPS technique appears to be a promising strategy to avoid it, however no
      experimental studies supporting this procedure have been previously described.
      The aim was to develop an experimental model of ALPPS in rats. METHOD:
      Experimental. A total of 30 Sprague Dawley rats were used. To develop the ALPPS
      procedure, ligation of the left portal branch of the middle lobe (LM) was
      performed. This demarcates the left side (SILM) from the right side (SDLM);
      parenchyma transection was performed following the demarcated line. The animal's
      weight, volume and weight of both LM were analyzed. Sacrifice at 3, 7 and 14 days
      after the procedure (10 per group) was performed. RESULTS: No bleeding or ascites
      were observed during the postoperative period. The LM increased by 24.1, 86.9 and
      120.4% at 3, 7 and 14 days. The SDLM increased by 34.4, 78.8 and 102.0% at 3, 7
      and 14 days. The SILM decreased 42.6, 64.8, and 79.3% at day 3, 7 and 14 days
      respectively. CONCLUSION: The ALPPS procedure can be performed in rats, achieving
      the expected results. Comparison studies to 2 staged hepatectomy will be
      necessary.

PMID- 25064518
TI  - [Sclerosing mucoepidermoid carcinoma of the thyroid gland with eosinophilia].

PMID- 25064519
TI  - Late diagnosis of occult gallbladder carcinoma by an implant in a laparoscopic
      trocar site.

PMID- 25064520
TI  - Exceptional use of a surgical oxidized cellulose polymer taponade in a patient
      with hemosuccus pancreaticus.

PMID- 25064521
TI  - Gun-shot wound and peripheral arterial embolism.

PMID- 25064522
TI  - Embolization of Intercostal Arteries in Iatrogenic Haemothorax.

PMID- 25064523
TI  - Should the diagnostic and therapeutic protocols for adrenal incidentalomas be
      changed?
AB  - BACKGROUND: The prevalence of adrenal incidentalomas is increasing with the aging
      of the population and the use of high resolution imaging technics. Current
      protocols propose a comprehensive monitoring of their functional and
      morphological state, but with no conclusive clinical evidence that endorses it.
      METHOD: Retrospective study of 96 patients diagnosed with adrenal incidentaloma
      between 2008 and 2012. We evaluated clinical, functional and imaging at baseline
      and during follow-up. RESULTS: Initially, 9 cases were surgically removed: 4 due
      to hyperfunction (2 Cushing syndromes and 2 pheochromocytomas) and 5 due to size
      larger than 4cm. During follow-up one case of pheochromocytoma was diagnosed and
      another grew more than 1cm, needing surgery. In 98.86% of nonfunctional and
      benign lesions, there was no functional and/or morphological changes in the final
      evaluation. CONCLUSIONS: The results of our study challenge the validity of
      current diagnostic-therapeutic protocols of incidentalomas, which should be
      reassessed in prospective studies taking into account efficiency characteristics.

PMID- 25064524
TI  - Diversity of interferon inducible Mx gene in horses and association of variations
      with susceptibility vis-a-vis resistance against equine influenza infection.
AB  - Equine influenza (EI) is primarily an infection of the upper respiratory tract
      and is one of the major infectious respiratory diseases of economic importance in
      equines. Re-emergence of the disease, species jumping by H3N8 virus in canines
      and possible threat of human pandemic due to the unpredictable nature of the
      virus have necessitated research on devising strategies for preventing the
      disease. The myxovirus resistance protein (Mx) has been reported to confer
      resistance to Orthomyxo virus infection by modifying cellular functions needed
      along the viral replication pathway. Polymorphisms and differential antiviral
      activities of Mx gene have been reported in pigs and chicken. Here we report the
      diversity of Mx gene, its expression in response to stimulation with interferon
      (IFN) alpha/beta and their association with EI resistance and susceptibility in
      Marwari horses. Blood samples were collected from horses declared positive for
      equine influenza and in contact animals with a history of no clinical signs. Mx
      gene was amplified by reverse transcription from total RNA isolated from
      peripheral blood mononuclear cells (PBMCs) stimulated with IFN alpha/beta using
      gene specific primers. The amplified gene products from representative samples
      were cloned and sequenced. Nucleotide sequences and deduced amino acid sequences
      were analyzed. Out of a total 24 amino acids substitutions sorting intolerant
      from tolerant (SIFT) analysis predicted 13 substitutions with functional
      consequences. Five substitutions (V67A, W123L, E346Y, N347Y, S689N) were observed
      only in resistant animals. Evolutionary distances based on nucleotide sequences
      with in equines ranged between 0.3-2.0% and 20-24% with other species. On
      phylogenetic analysis all equine sequences clustered together while other species
      formed separate clades. 

PMID- 25064525
TI  - Toward a method for tracking virus evolutionary trajectory applied to the
      pandemic H1N1 2009 influenza virus.
AB  - In 2009 a novel pandemic H1N1 influenza virus (H1N1pdm09) emerged as the first
      official influenza pandemic of the 21st century. Early genomic sequence analysis
      pointed to the swine origin of the virus. Here we report a novel computational
      approach to determine the evolutionary trajectory of viral sequences that uses
      data-driven estimations of nucleotide substitution rates to track the gradual
      accumulation of observed sequence alterations over time. Phylogenetic analysis
      and multiple sequence alignments show that sequences belonging to the resulting
      evolutionary trajectory of the H1N1pdm09 lineage exhibit a gradual accumulation
      of sequence variations and tight temporal correlations in the topological
      structure of the phylogenetic trees. These results suggest that our evolutionary
      trajectory analysis (ETA) can more effectively pinpoint the evolutionary history
      of viruses, including the host and geographical location traversed by each
      segment, when compared against either BLAST or traditional phylogenetic analysis
      alone. 

PMID- 25064527
TI  - Generation of clinical grade human bone marrow stromal cells for use in bone
      regeneration.
AB  - In current orthopaedic practice, there is a need to increase the ability to
      reconstruct large segments of bone lost due to trauma, resection of tumors and
      skeletal deformities, or when normal regenerative processes have failed such as
      in non-unions and avascular necrosis. Bone marrow stromal cells (BMSCs, also
      known as bone marrow-derived mesenchymal stem cells), when used in conjunction
      with appropriate carriers, represent a means by which to achieve bone
      regeneration in such cases. While much has been done at the bench and in pre
      clinical studies, moving towards clinical application requires the generation of
      clinical grade cells. What is described herein is an FDA-approved cell
      manufacturing procedure for the ex vivo expansion of high quality, biologically
      active human BMSCs. This article is part of a Special Issue entitled Stem Cells
      and Bone. 

PMID- 25064526
TI  - Retinaldehyde dehydrogenase 1 deficiency inhibits PPARgamma-mediated bone loss
      and marrow adiposity.
AB  - PPARgamma, a ligand-activated nuclear receptor, regulates fundamental aspects of
      bone homeostasis and skeletal remodeling. PPARgamma-activating anti-diabetic
      thiazolidinediones in clinical use promote marrow adiposity, bone loss, and
      skeletal fractures. As such, delineating novel regulatory pathways that modulate
      the action of PPARgamma, and its obligate heterodimeric partner RXR, may have
      important implications for our understanding and treatment of disorders of low
      bone mineral density. We present data here establishing retinaldehyde
      dehydrogenase 1 (Aldh1a1) and its substrate retinaldehyde (Rald) as novel
      determinants of PPARgamma-RXR actions in the skeleton. When compared to wild type
      (WT) controls, retinaldehyde dehydrogenase-deficient (Aldh1a1(-/-)) mice were
      protected against bone loss and marrow adiposity induced by either the
      thiazolidinedione rosiglitazone or a high fat diet, both of which potently
      activate the PPARgamma-RXR complex. Consistent with these results, Rald, which
      accumulates in vivo in Aldh1a1(-/-) mice, protects against rosiglitazone-mediated
      inhibition of osteoblastogenesis in vitro. In addition, Rald potently inhibits in
      vitro adipogenesis and osteoclastogenesis in WT mesenchymal stem cells (MSCs) and
      hematopoietic stem cells (HSCs) respectively. Primary Aldh1a1(-/-) HSCs also
      demonstrate impaired osteoclastogenesis in vitro compared to WT controls.
      Collectively, these findings identify Rald and retinoid metabolism through
      Aldh1a1 as important novel modulators of PPARgamma-RXR transactivation in the
      marrow niche. 

PMID- 25064528
TI  - Discussion.

PMID- 25064529
TI  - Carotid artery stenting has increased risk of external carotid artery occlusion
      compared with carotid endarterectomy.
AB  - OBJECTIVE: The external carotid artery (ECA) can be an important source of
      cerebral blood flow in cases of high-grade internal carotid artery stenosis or
      occlusion. However, the treatment of the ECA is fundamentally different between
      carotid endarterectomy (CEA) and carotid artery stenting (CAS). CEA is routinely
      associated with endarterectomy of the ECA, whereas CAS excludes the ECA from
      direct flow. We hypothesize that these differences make ECA occlusion more common
      after CAS. Further, the impact of CAS on blood flow into the ECA is interesting
      because the flow from the stent into the ECA is altered in a way that may promote
      local inflammation and may influence in-stent restenosis (ISR). Thus, our
      objective was to use our institutional database to identify whether CAS increased
      the rate of ECA occlusion and, if it did, whether ECA occlusion was associated
      with ISR. METHODS: Patients undergoing CAS or CEA from February 2007 to February
      2012 were identified from our institutional carotid therapy database.
      Preoperative and postoperative images of patients who followed up in our
      institution were included in the analysis of ECA occlusion and rates of ISR.
      RESULTS: There were 210 (67%) CAS patients and 207 (60%) CEA patients included in
      this analysis. Despite CAS patients being younger (68 vs 70 years), having
      shorter follow-up (12.5 vs 56.2 months), and being more likely to take
      clopidogrel (97% vs 35%), they had an increased rate of ECA occlusion (3.8%)
      compared with CEA patients (0.4%). CAS patients who went on to ECA occlusion had
      an increased incidence of prior neck irradiation (50% vs 15%; P = .03), but we
      did not identify an association of ECA occlusion with ISR >50%. CONCLUSIONS:
      Whereas prior publications have identified increased rates of external carotid
      stenosis, this is the first demonstration of increased ECA occlusion after CAS.
      However, ECA occlusion is uncommon (~4%) and did not have an association with ISR
      >50%. Future work modeling ECA flow patterns before and after CAS will be used to
      further test this interaction.

PMID- 25064530
TI  - Vesicles formed by mixed catanionic surfactants as novel pseudostationary phase
      in electrokinetic chromatography.
AB  - In this paper, a novel pseudostationary phase (PSP), the vesicle formed from
      octyltriethylammonium bromide (C8NE3Br) and sodium dodecyl benzene sulfonate
      (SDBS), has been developed in electrokinetic chromatography (EKC).
      Physicochemical parameters of the mixture of catanionic surfactants such as zeta
      potential and size of the aggregates were characterized as the molar ratio of
      C8NE3Br to SDBS varied from 2:8 to 8:2 and total concentration of surfactants
      fixed at 20mM. At any ratio mentioned above, zeta potential of mixture of
      catanionic surfactants remained negative. The absolute values of zeta potential
      were even larger than in only SDBS system as the molar ratio of C8NE3Br to SDBS
      less than 4:6, and they decreased as increasing the ratio of cationic
      surfactants. The size of the aggregates became smaller as the ratio was close to
      1. Unexpectedly, the size was smallest at ratio of 3:7 and 6:4, instead of at
      5:5. Notably, coagulation did not occur in the catanionic system at any
      proportion of each other. TEM testified the formation of vesicles. The
      performance of the vesicle as PSP was evaluated by separating eight kinds of
      corticosteroids with EKC, these analytes were separated completely without any
      additives. Compared with SDS microemulsion modified with ionic liquid (IL) and
      polymeric micelle, the novel vesicle PSP had better separation performances. 

PMID- 25064531
TI  - Experimental design-guided development of a stereospecific capillary
      electrophoresis assay for methionine sulfoxide reductase enzymes using a
      diastereomeric pentapeptide substrate.
AB  - A capillary electrophoresis method has been developed and validated to evaluate
      the stereospecific activity of recombinant human methionine sulfoxide reductase
      enzymes employing the C-terminally dinitrophenyl-labeled N-acetylated
      pentapeptide ac-KIFM(O)K-Dnp as substrate (M(O)=methionine sulfoxide). The
      separation of the ac-KIFM(O)K-Dnp diastereomers and the reduced peptide ac-KIFMK
      Dnp was optimized using experimental design with regard to the buffer pH, buffer
      concentration, sulfated beta-cyclodextrin and 15-crown-5 concentration as well as
      capillary temperature and separation voltage. A fractional factorial response IV
      design was employed for the identification of the significant factors and a five
      level circumscribed central composite design for the final method optimization.
      Resolution of the peptide diastereomers as well as analyte migration time served
      as responses in both designs. The resulting optimized conditions included 50mM
      Tris buffer, pH 7.85, containing 5mM 15-crown-5 and 14.3mg/mL sulfated beta
      cyclodextrin, at an applied voltage of 25kV and a capillary temperature of 21.5
      degrees C. The assay was subsequently applied to the determination of the
      stereospecificity of recombinant human methionine sulfoxide reductases A and B2.
      The Michaelis-Menten kinetic data were determined. The pentapeptide proved to be
      a good substrate for both enzymes. Furthermore, the first separation of
      methionine sulfoxide peptide diastereomers is reported. 

PMID- 25064532
TI  - Probing and quantifying DNA-protein interactions with asymmetrical flow field
      flow fractionation.
AB  - Tools capable of measuring binding affinities as well as amenable to downstream
      sequencing analysis are needed for study of DNA-protein interaction, particularly
      in discovery of new DNA sequences with affinity to diverse targets. Asymmetrical
      flow field-flow fractionation (AF4) is an open-channel separation technique that
      eliminates interference from column packing to the non-covalently bound complex
      and could potentially be applied for study of macromolecular interaction. The
      recovery and elution behaviors of the poly(dA)n strand and aptamers in AF4 were
      investigated. Good recovery of ssDNAs was achieved by judicious selection of the
      channel membrane with consideration of the membrane pore diameter and the radius
      of gyration (Rg) of the ssDNA, which was obtained with the aid of a Molecular
      Dynamics tool. The Rg values were also used to assess the folding situation of
      aptamers based on their migration times in AF4. The interactions between two
      ssDNA aptamers and their respective protein components were investigated. Using
      AF4, near-baseline resolution between the free and protein-bound aptamer
      fractions could be obtained. With this information, dissociation constants of
      ~16nM and ~57nM were obtained for an IgE aptamer and a streptavidin aptamer,
      respectively. In addition, free and protein-bound IgE aptamer was extracted from
      the AF4 eluate and amplified, illustrating the potential of AF4 in screening
      ssDNAs with high affinity to targets. Our results demonstrate that AF4 is an
      effective tool holding several advantages over the existing techniques and should
      be useful for study of diverse macromolecular interaction systems. 

PMID- 25064533
TI  - Profiling of drug binding proteins by monolithic affinity chromatography in
      combination with liquid chromatography-tandem mass spectrometry.
AB  - A new approach for proteome-wide profiling drug binding proteins by using
      monolithic capillary affinity chromatography in combination with HPLC-MS/MS is
      reported. Two immunosuppresive drugs, namely FK506 and cyclosporin A, were
      utilized as the experimental models for proof-of-concept. The monolithic
      capillary affinity columns were prepared through a single-step copolymerization
      of the drug derivatives with glycidyl methacrylate and ethylene dimethacrylate.
      The capillary chromatography with the affinity monolithic column facilitates the
      purification of the drug binding proteins from the cell lysate. By combining the
      capillary affinity column purification and the shot-gun proteomic analysis,
      totally 33 FK506- and 32 CsA-binding proteins including all the literature
      reported target proteins of these two drugs were identified. Among them, two
      proteins, namely voltage-dependent anion-selective channel protein 1 and
      serine/threonine-protein phosphatase PGAM5 were verified by using the recombinant
      proteins. The result supports that the monolithic capillary affinity
      chromatography is likely to become a valuable tool for profiling of binding
      proteins of small molecular drugs as well as bioactive compounds. 

PMID- 25064534
TI  - A novel method for rapid determination of total solid content in viscous liquids
      by multiple headspace extraction gas chromatography.
AB  - This work demonstrates a novel method for rapid determination of total solid
      content in viscous liquid (polymer-enriched) samples. The method is based
      multiple headspace extraction gas chromatography (MHE-GC) on a headspace vial at
      a temperature above boiling point of water. Thus, the trend of water loss from
      the tested liquid due to evaporation can be followed. With the limited MHE-GC
      testing (e.g., 5 extractions) and a one-point calibration procedure (i.e.,
      recording the weight difference before and after analysis), the total amount of
      water in the sample can be determined, from which the total solid contents in the
      liquid can be calculated. A number of black liquors were analyzed by the new
      method which yielded results that closely matched those of the reference method;
      i.e., the results of these two methods differed by no more than 2.3%. Compared
      with the reference method, the MHE-GC method is much simpler and more practical.
      Therefore, it is suitable for the rapid determination of the solid content in
      many polymer-containing liquid samples. 

PMID- 25064535
TI  - Quantitative analysis of free and bonded forms of volatile sulfur compouds in
      wine. Basic methodologies and evidences showing the existence of reversible
      cation-complexed forms.
AB  - This paper examines first some basic aspects critical to the analysis of Volatile
      Sulfur Compounds (VSCs), such as the analytical characteristics of the GC-pFPD
      system and the stability of the different standard solutions required for a
      proper calibration. Following, a direct static headspace analytical method for
      the determination of exclusively free forms of VSCs has been developed. Method
      repeatability is better than 4%, detection limits for main analytes are below
      0.5MUgL(-1), and the method dynamic linear range (r(2)>0.99) is expanded by
      controlling the split ratio in the chromatographic inlet to cover the natural
      range of occurrence of these compounds in wines. The method gives reliable
      estimates of headspace concentrations but, as expected, suffers from strong
      matrix effects with recoveries ranging from 0 to 100% or from 60 to 100 in the
      cases of H2S and the other mercaptans, respectively. This demonstrates the
      existence of strong interactions of these compounds with different matrix
      components. The complexing ability of Cu(2+) and to a lower extent Fe(2+) and
      Zn(2+) has been experimentally checked. A previously developed method in which
      the wine is strongly diluted with brine and the volatiles are preconcentrated by
      HS-SPME, was found to give a reliable estimation of the total amount
      (free+complexed) of mercaptans, demonstrating that metal-mercaptan complexes are
      reversible. The comparative analysis of different wines by the two procedures
      reveals that in normal wines H2S and methanethiol can be complexed at levels
      above 99%, with averages around 97% for H2S and 75% for methanethiol, while
      thioethers such as dimethyl sulfide (DMS) are not complexed. Overall, the
      proposed strategy may be generalized to understand problems caused by VSCs in
      different matrices. 

PMID- 25064536
TI  - Octapeptide-based affinity chromatography of human immunoglobulin G: comparisons
      of three different ligands.
AB  - In an earlier work, we have developed a biomimetic design strategy based on the
      human IgG (hIgG)-Protein A interactions and identified an affinity ligand for
      hIgG, FYWHCLDE, which ranked top one in a pool of 14 potential candidates.
      Herein, two more octapeptides, FYCHWALE and FYCHTIDE, were identified, and the
      binding and purification of hIgG on the affinity columns packed with the three
      octapeptide-modified Sepharose gels were extensively studied and compared to find
      more effective octapeptide-based affinity ligands. It was found that all the
      three ligands bound hIgG and Fc fragment but barely bound Fab fragment, and the
      binding to hIgG and Fc was mainly by electrostatic interactions. The optimum
      binding pH values for the three ligands were different from each other, but kept
      in the range of 5.0-6.0. Ligand binding competition revealed that the binding
      sites on hIgG for the three octapeptides were similar to those for Protein A.
      Adsorption isotherms revealed that hIgG binding capacity was in the range of 64
      104mg/mL drained gel in the order of FYWHCLDE>FYCHWALE>FYCHTIDE. Then,
      purifications of hIgG and human monoclonal antibody from human serum and cell
      culture supernatant, respectively, were achieved with the three affinity columns
      at high purities and recovery yields. Finally, the molecular basis for the
      binding affinity of the peptides for the Fc fragment of hIgG was elucidated by
      molecular dynamics simulations. 

PMID- 25064537
TI  - Detailed compositional characterization of plastic waste pyrolysis oil by
      comprehensive two-dimensional gas-chromatography coupled to multiple detectors.
AB  - The detailed compositional characterization of plastic waste pyrolysis oil was
      performed with comprehensive two-dimensional GC (GC*GC) coupled to four different
      detectors: a flame ionization detector (FID), a sulfur chemiluminescence detector
      (SCD), a nitrogen chemiluminescence detector (NCD) and a time of flight mass
      spectrometer (TOF-MS). The performances of different column combinations were
      assessed in normal i.e. apolar/mid-polar and reversed configurations for the
      GC*GC-NCD and GC*GC-SCD analyses. The information obtained from the four
      detectors and the use of internal standards, i.e. 3-chlorothiophene for the FID
      and the SCD and 2-chloropyridine for the NCD analysis, enabled the identification
      and quantification of the pyrolysis oil in terms of both group type and carbon
      number: hydrocarbon groups (n-paraffins, iso-paraffins, olefins and naphthenes,
      monoaromatics, naphthenoaromatics, diaromatics, naphthenodiaromatics,
      triaromatics, naphthenotriaromatics and tetra-aromatics), nitrogen (nitriles,
      pyridines, quinolines, indole, caprolactam, etc.), sulfur (thiols/sulfides,
      thiophenes/disulfides, benzothiophenes, dibenzothiophenes, etc.) and oxygen
      containing compounds (ketones, phenols, aldehydes, ethers, etc.). Quantification
      of trace impurities is illustrated for indole and caprolactam. The analyzed
      pyrolysis oil included a significant amount of nitrogen containing compounds
      (6.4wt%) and to a lesser extent sulfur containing compounds (0.6wt%). These
      nitrogen and sulfur containing compounds described approximately 80% of the total
      peak volume for respectively the NCD and SCD analysis. TOF-MS indicated the
      presence of the oxygen containing compounds. However only a part of the oxygen
      containing compounds (2.5wt%) was identified because of their low concentrations
      and possible overlap with the complex hydrocarbon matrix as no selective detector
      or preparative separation for oxygen compounds was used. 

PMID- 25064538
TI  - Adjunctive lacosamide--5 years' clinical experience.
AB  - PURPOSE: In 2008, lacosamide (LCM) was licensed in Europe for the adjunctive
      treatment of focal-onset seizures. At that time a prospective audit was initiated
      at the Western Infirmary to assess outcomes with this antiepileptic drug (AED) in
      everyday clinical practice. METHODS: A total of 160 patients (74 M; 86 F, aged 14
      74 years [median 42 years]) with uncontrolled focal-onset seizures (median
      monthly frequency 1; range 1-300) were started on LCM. After 12 weeks on stable
      AED doses (median 1 AED; range 1-4), LCM was added and the dose titrated as
      appropriate with a target range of 200-400 mg/day. Review took place every 6-8
      weeks until 1 of 4 end-points was reached: seizure freedom for 6 months on a
      given LCM dose; >=50% (responder) or <50% (marginal benefit) seizure reduction
      over 6 months compared with baseline on the highest tolerated LCM dose;
      withdrawal of LCM due to lack of efficacy, side effects, or both. RESULTS: Of the
      160 patients, 35 (21.9%) remained seizure-free for at least 6 months on a stable
      LCM dose, while 35 (21.9%) had a >=50% reduction in seizure frequency and 54
      (33.7%) reported a marginal benefit. Five patients became seizure-free on LCM
      monotherapy following withdrawal of their initial treatment. Outcomes were
      similar for patients taking LCM with traditional sodium blocking agents (n=56; 43
      [76%] continued LCM) compared to those who also received AEDs with other
      mechanisms (n=84; 64 [76%] continued LCM). LCM was discontinued in 36 (22.5%)
      patients because of lack of efficacy (n=24, 15%) or side effects (n=12; 7.5%).
      Commonest side effects leading to withdrawal were nausea and vomiting, dizziness,
      sedation, headaches, tremor, and ataxia, particularly for patients also taking
      sodium valproate. CONCLUSION: LCM is a well-tolerated and effective AED for focal
      onset seizures with or without secondary generalisation, regardless of
      concomitant treatment. Commonest dose-related side effects were neurotoxic in
      nature.

PMID- 25064539
TI  - Optimisation and standardisation of functional immune assays for striped catfish
      (Pangasianodon hypophthalmus) to compare their immune response to live and heat
      killed Aeromonas hydrophila as models of infection and vaccination.
AB  - Aquaculture production of Pangasianodon hypophthalmus is growing rapidly in South
      East Asia, especially in Vietnam. As it is a relatively new aquaculture species
      there are few reports evaluating its immune response to pathogens. Thus,
      functional assays for P. hypophthalmus were optimised to evaluate both innate and
      adaptive immune responses, and were then used to examine immune response
      following stimulation with live and heat-killed Aeromonas hydrophila. These were
      used as models of infection and vaccination, respectively. Four treatment groups
      were used, including a control group, a group injected intraperitonally (IP) with
      adjuvant only, a group injected with heat-killed A. hydrophila (1 * 10(9) cfu ml(
      1) mixed with adjuvant), and a group injected with a subclinical dose of live A.
      hydrophila. Samples were collected at 0, 1, 3, 7, 14 and 21 days post-injection
      (d.p.i.) to assess their immune response. The results indicated that challenge
      with live or dead bacteria stimulated the immune response in P. hypophthalmus
      significantly above the levels observed in control groups with respect to
      specific antibody titre, plasma lysozyme and peroxidase activity, and
      phagocytosis by head kidney macrophages at 7 or/and 14 d.p.i. At 21 d.p.i., total
      and specific antibody (IgM) levels and plasma lysozyme activity in fish injected
      with either live or dead A. hydrophila were significantly different to the
      control groups. Differential immune responses were observed between fish injected
      with either live or dead bacteria, with live A. hydrophila significantly
      stimulating an increase in WBC counts and plasma peroxidase activity at 3 d.p.i.,
      with the greatest increase in WBC counts noted at 21 d.p.i. and in phagocytosis
      at 14 d.p.i. By 21 d.p.i. only the macrophages from fish injected with dead A.
      hydrophila showed significantly stimulation in their respiratory burst activity.
      This study provides basic information on the immune response in pangasius catfish
      that can be useful in the health control of this species.

PMID- 25064540
TI  - Resveratrol mitigate structural changes and hepatic stellate cell activation in
      N'-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage.
AB  - Resveratrol, a polyphenol, found in skin of red grapes, peanuts and berries
      possesses anti-inflammatory, anti-carcinogenic and lipid modulation properties.
      Here, we demonstrate in vivo antifibrotic activity of resveratrol in a mammalian
      model, wherein hepatic fibrosis was induced by N'-nitrosodimethylamine (NDMA)
      administration. Apart from being a potent hepatotoxin, NDMA is a known mutagen
      and carcinogen, as well. To induce hepatic fibrosis, rats were administered NDMA
      (i.p.) in 10mg/kgb.wt thrice/week for 21 days. Another group of animals received
      resveratrol supplement (10mg/kgb.wt) subsequent to NDMA administration and were
      sacrificed weekly. The changes in selected biomarkers were monitored to compare
      profibrotic effects of NDMA and antifibrotic activity of resveratrol. The
      selected biomarkers were: sera transaminases, ALP, bilirubin, liver glycogen,
      LPO, SOD, protein carbonyl content, ATPases (Ca(2+), Mg(2+), Na(+)/K(+)) and
      hydroxyproline/collagen content. Alterations in liver architecture were assessed
      by H&E, Masson's trichrome and reticulin staining of liver biopsies. Immuno
      histochemistry and immunoblotting were employed to examine expression of alpha
      SMA. Our results demonstrate that during NDMA-induced liver fibrosis
      transaminases, ALP, bilirubin, hydroxyproline and liver collagen increases, while
      liver glycogen is depleted. The decline in SOD (>65%) and ATPases, which were
      concomitant with the elevation in MDA and protein carbonyls, strongly indicate
      oxidative damage. Fibrotic transformation of liver in NDMA-treated rats was
      verified by histopathology, immuno-histochemistry and immunoblotting data, with
      the higher expressivity of alpha-SMA-positive HSCs being most established
      diagnostic immuno-histochemical marker of HSCs. Resveratrol-supplement
      refurbished liver architecture by significantly restoring levels of biomarkers of
      oxidative damage (MDA, SOD, protein carbonyls and membrane-bound ATPases).
      Therefore, we conclude that antifibrotic effect of resveratrol is due to
      restrained oxidative damage and down-regulation of alpha-SMA, which inhibits HSC
      activation to obstruct liver fibrosis.

PMID- 25064541
TI  - Elemental mapping in achromatic atomic-resolution energy-filtered transmission
      electron microscopy.
AB  - We present atomic-resolution energy-filtered transmission electron microscopy
      (EFTEM) images obtained with the chromatic-aberration-corrected FEI Titan PICO at
      the Ernst-Ruska Centre, Julich, Germany. We find qualitative agreement between
      experiment and simulation for the background-subtracted EFTEM images of the Ti
      L2,3 and O-K edges for a specimen of SrTiO3 oriented down the [110] zone axis.
      The simulations utilize the transition potential formulation for inelastic
      scattering, which permits a detailed investigation of contributions to the EFTEM
      image. We find that energy-filtered images of the Ti-L2,3 and O-K edges are
      lattice images and that the background-subtracted core-loss maps may not be
      directly interpretable as elemental maps. Simulations show that this is a result
      of preservation of elastic contrast, whereby the qualitative details of the image
      are determined primarily by elastic, coherent scattering. We show that this
      effect places a constraint on the range of specimen thicknesses which could
      theoretically yield directly useful elemental maps. In general, interpretation of
      EFTEM images is ideally accompanied by detailed simulations. 

PMID- 25064542
TI  - A 60-year-old man with chronic cough and green sputum.

PMID- 25064543
TI  - Nausea, vomiting, and weight loss: common symptoms of an uncommon disease.

PMID- 25064544
TI  - An unusual cutaneous manifestation in a patient with cystic fibrosis.

PMID- 25064545
TI  - Multiple liver lesions in a patient with positive hepatitis C serology and
      elevated AFP: is it HCC?

PMID- 25064546
TI  - A female patient with persistent epigastric pain for 1 week.

PMID- 25064547
TI  - Yellow flank discoloration and abdominal distension in an infant.

PMID- 25064548
TI  - A rare cause of noncirrhotic intrahepatic portal hypertension.

PMID- 25064549
TI  - An uncommon combination of polyps.

PMID- 25064550
TI  - Atypical acute liver failure in acute myeloid leukemia.

PMID- 25064551
TI  - Cholestatic hepatitis and weight loss in a Vietnamese immigrant.

PMID- 25064552
TI  - The International Confederation of Midwives 30th Triennial Congress--'Midwives:
      improving women's health globally'.

PMID- 25064554
TI  - Targeted multimodal imaging modalities.
AB  - Molecular imaging non-invasively visualizes and characterizes the biologic
      functions and mechanisms in living organisms at a molecular level. In recent
      years, advances in imaging instruments, imaging probes, assay methods, and
      quantification techniques have enabled more refined and reliable images for more
      accurate diagnoses. Multimodal imaging combines two or more imaging modalities
      into one system to produce details in clinical diagnostic imaging that are more
      precise than conventional imaging. Multimodal imaging offers complementary
      advantages: high spatial resolution, soft tissue contrast, and biological
      information on the molecular level with high sensitivity. However, combining all
      modalities into a single imaging probe involves problems yet to be solved due to
      the requirement of high dose contrast agents for a component of imaging modality
      with low sensitivity. The introduction of targeting moieties into the probes
      enhances the specific binding of targeted multimodal imaging modalities and
      selective accumulation of the imaging agents at a disease site to provide more
      accurate diagnoses. An extensive list of prior reports on the targeted multimodal
      imaging probes categorized by each modality is presented and discussed. In
      addition to accurate diagnosis, targeted multimodal imaging agents carrying
      therapeutic medications make it possible to visualize the theranostic effect and
      the progress of disease. This will facilitate the development of an imaging
      guided therapy, which will widen the application of the targeted multimodal
      imaging field to experiments in vivo. 

PMID- 25064556
TI  - Ultrasound-assisted extraction of polysaccharide from Nephelium lappaceum L.
      fruit peel.
AB  - In this study, ultrasound-assisted extraction technology was employed to
      investigate and optimize the crude polysaccharide extraction from Nephelium
      lappaceum L. fruit peel using three levels, four factors (LS ratio, ultrasonic
      power, extraction temperature and extraction time) Box-Behnken response surface
      design. The results showed that highest polysaccharide yield of 8.31% was
      obtained with an LS ratio of 32:1 ml:g, ultrasonic power of 110 W, extraction
      temperature of 53 degrees C and extraction time of 41 min. The experimental yield
      of polysaccharide (8.29+/-0.03%) at optimal condition was well agreed with the
      predicted value. Fourier transform infrared spectroscopy (FTIR) was used for the
      identification of functional groups present in the extracted polysaccharide. The
      results suggest that ultrasound-assisted extraction could be a good alternative
      for the extraction of polysaccharide from N. lappaceum L. fruit peel at
      industrial level.

PMID- 25064555
TI  - Characterisation of a chitinase from Pseudoalteromonas sp. DL-6, a marine
      psychrophilic bacterium.
AB  - In this study, we isolated a new psychrophilic bacterium, Pseudoalteromonas sp.
      DL-6 from marine sediments, which grew well on chitin-containing plates at 4
      degrees C. One endo-type chitinase gene, chiA, was cloned from the genomic DNA of
      this bacterium and heterologously expressed in Escherichia coli BL21 (DE3). ChiA
      showed very high catalytic activity, even at 4 degrees C, and exhibited maximal
      activity on a chitinous substrate at pH 8.0 and 20 degrees C. Kinetic studies
      indicated that ChiA has a greater catalytic efficiency on 4-methylumbelliferyl
      beta-D-N,N',N"-triacetylchitotriose[4-MU(GlcNAc)3] than on 4-methylumbelliferyl
      beta-D-N,N'-diacetylchitobioside[4-MU(GlcNAc)2]. Electrospray ionisation mass
      spectrometry (ESI-MS) analysis showed that the hydrolysis products of powdered
      chitin after ChiA digestion consisted of a series of chitin oligomers with
      different degrees of polymerisation. The ChiA mode of action was also examined
      using (GlcNAc)2-6 as a substrate, and the results suggested that ChiA is a non
      processive endo-type chitinase.

PMID- 25064557
TI  - Addition of 1,3-beta-D-glucan to chitosan-based composites enhances osteoblast
      adhesion, growth, and proliferation.
AB  - The aim of this work was to prove using two osteoblastic cell lines that addition
      of bacterial 1,3-beta-D-glucan to chitosan-based biocomposites significantly
      enhances adhesion, growth, and proliferation of osteoblast cells. Cytotoxicity of
      materials was evaluated indirectly using fluid extracts and by direct-contact
      method using live/dead double fluorescent staining. Cell adhesion was determined
      quantitatively by LDH total test and cell proliferation was assessed by confocal
      microscope observation. Obtained data clearly prove that addition of 1,3-beta-D
      glucan to the bi-component chitosan/bioceramic materials significantly enhances
      adhesion, growth, and proliferation of osteoblast cells. The results demonstrated
      that all investigated biomaterials were non-toxic and allowed for cell
      attachment. However, significantly better osteoblast growth was observed on
      scaffolds containing 1,3-beta-D-glucan. Thus, it may be inferred that scaffolds
      modified with glucan are more promising materials for bone tissue engineering
      application than bi-component chitosan/bioceramic composites.

PMID- 25064553
TI  - Fluorescent imaging of cancerous tissues for targeted surgery.
AB  - To maximize tumor excision and minimize collateral damage are the primary goals
      of cancer surgery. Emerging molecular imaging techniques have made "image-guided
      surgery" developed into "molecular imaging-guided surgery", which is termed as
      "targeted surgery" in this review. Consequently, the precision of surgery can be
      advanced from tissue-scale to molecule-scale, enabling "targeted surgery" to be a
      component of "targeted therapy". Evidence from numerous experimental and clinical
      studies has demonstrated significant benefits of fluorescent imaging in targeted
      surgery with preoperative molecular diagnostic screening. Fluorescent imaging can
      help to improve intraoperative staging and enable more radical cytoreduction,
      detect obscure tumor lesions in special organs, highlight tumor margins, better
      map lymph node metastases, and identify important normal structures
      intraoperatively. Though limited tissue penetration of fluorescent imaging and
      tumor heterogeneity are two major hurdles for current targeted surgery,
      multimodality imaging and multiplex imaging may provide potential solutions to
      overcome these issues, respectively. Moreover, though many fluorescent imaging
      techniques and probes have been investigated, targeted surgery remains at a proof
      of-principle stage. The impact of fluorescent imaging on cancer surgery will
      likely be realized through persistent interdisciplinary amalgamation of research
      in diverse fields. 

PMID- 25064558
TI  - Microwave-assisted extraction of polysaccharides from mulberry leaves.
AB  - In this study, microwave-assisted extraction (MAE) of polysaccharides from
      mulberry leaves was investigated using response surface methodology (RSM). The
      effects of three extraction factors on the yield of polysaccharides was examined.
      The results showed that optimum extraction conditions were determined as follows:
      weight of the sample of 20 g, microwave power of 170 W, extraction time of 10
      min. Under these optimal extraction conditions, polysaccharide yield was found to
      be 9.41%. Three factors-three level Box-Behnken response surface design (BBD)
      coupled with RSM was used to model the extraction process. ANOVA was used to
      examine the statistical significance of the developed model. Extracted
      polysaccharide was analyzed using Fourier transform infrared (FT-IR)
      spectroscopy.

PMID- 25064559
TI  - Physiological adjustments of haematological profile during the last trimester of
      pregnancy and the early post partum period in mares.
AB  - The aim of the study was to assess changes in some haematological parameters of
      periparturient mares from the last three months of pregnancy until the third week
      after foaling. The study was carried out on 15 healthy pregnant mares (Group A)
      and 7 healthy non-pregnant non-lactating mares (Group B). Blood samples were
      collected by jugular venipuncture into EDTA tubes and tested for Haematocrit
      (Hct), Red Blood Cell (RBC), Haemoglobin (Hb), Platelets (Plt) and White Blood
      Cell (WBC). Peripheral blood smears were also performed to assess changes in the
      leucocyte differential count. Group A showed a progressive reduction in Hct and
      Hb levels over the experimental period, whereas Plt and WBC (P<0.05) peaked at
      parturition. Among WBC, neutrophils increased until parturition when lymphocytes
      reached the lowest values. The statistical analysis also revealed significant
      interactions time * pregnancy on Hb (P<0.001), WBC (P<0.001), neutrophils
      (P<0.001) and lymphocytes (P<0.001). Analysing the last trimester of pregnancy
      and the first post partum period the present study provides suitable information
      about the influence of peripartum on mares' haematological parameters.

PMID- 25064560
TI  - Influence of lactation length and gonadotrophins administered at weaning on
      fertility of primiparous sows.
AB  - The aim of this study was to determine the effect of lactation length and
      treatment with gonadotrophins at weaning on reproductive performance of
      primiparous sows. After 3 wk of lactation, primiparous sows were either weaned
      (W3; n=273) or received a 7-d-old foster litter for a further 14 d of suckling
      (W5; n=199). At final weaning (3 wk or 5 wk lactation) sows were randomly
      assigned to receive an injection of 400 IU equine chorionic gonadotrophin plus
      200 IU human chorionic gonadotrophin (PG600((r)); W3 + P; n=108 and W5 + P; n=96)
      or no injection (W3; n=165 and W5; n=103). Sows were inseminated at first
      observed estrus after final weaning and 24h later. The proportion of sows showing
      estrus by 6 d post-weaning was greater (P<0.01) for W3+P (86%) compared to W3
      (64%), however, there was not a difference (P=0.13) for W5 + P (79.4%) compared
      to W5 (69.1%). There was no effect of either lactation length or gonadotrophin
      treatment on farrowing rates or on the proportion of sows culled before breeding.
      Total born litter size was smaller (P=0.05) for W3 + P (11.7 +/- 0.4) compared to
      W3 (12.6 +/- 0.3). However, sows that lactated for 35 d had larger litters than
      sows that lactated for 21 d regardless of gonadotrophin treatment (14 +/- 0.5 and
      14.5 +/- 0.4 for W5+P and W5, respectively; P<0.001). These data indicate that
      for primiparous sows, a longer lactation improves total born litter size at their
      next farrowing. Gonadotrophin treatment is useful in shortening the weaning to
      estrus interval but subsequent total born litter size may be negatively affected.

PMID- 25064561
TI  - Sperm selection by Capripure((r)) density-gradient centrifugation versus the
      dextran swim-up procedure in wild mountain ruminants.
AB  - This study compares the effectiveness of two methods of sperm selection -
      Capripure((r)) density-gradient centrifugation (DGC) and dextran swim-up (DSU) -
      in semen samples from Iberian ibex (Capra pyrenaica) and European mouflon (Ovis
      musimon). During the increasing photoperiod, Capripure((r)) DGC improved the
      percentage of sperm with progressive motility (P<0.05) in ibexes, and selected
      60.6% of the initial total number of spermatozoa contained in the ejaculate
      samples. In mouflon, Capripure((r)) DGC selection was unaffected by photoperiod,
      had no influence on any sperm variable, and selected 47.8% of the initial total
      number of mouflon spermatozoa in ejaculate samples. Photoperiod had no influence
      on the effectiveness of DSU in either ibexes or mouflons. In the ibexes, DSU
      reduced (P<0.05) the percentage of sperm cells with morphological abnormalities,
      but only selected 11.3% of the initial total number of spermatozoa in ejaculate
      samples. In the mouflons, DSU had no significant influence on any sperm variable,
      and selected 27.8% of the initial total number. Capripure((r)) DGC improved ibex
      and mouflon sperm motility (P<0.05) following 30min and 2h of post
      centrifugation, stress-inducing incubation, respectively. In both ibexes and
      mouflon, sperm cells showing non-progressive motility were found after only 20 h
      of post-centrifugation incubation following Capripure((r)) DGC selection. In
      conclusion, Capripure((r)) DGC would seem a useful method for selecting the best
      spermatozoa from both ibex and mouflon ejaculates.

PMID- 25064562
TI  - Mining, genetic mapping and expression analysis of EST-derived resistance gene
      homologs (RGHs) in cotton.
AB  - BACKGROUND: Cotton is the dominant textile crop and also serves as an important
      oil crop. An estimated 15% economic loss associated with cotton production in
      China has been caused by diseases, and no resistance genes have been cloned in
      this crop. Molecular markers developed from resistance gene homologues (RGHs)
      might be tightly linked with target genes and could be used for marker-assisted
      selection (MAS) or gene cloning. RESULTS: To genetically map expressed RGHs, 100
      potential pathogenesis-related proteins (PRPs) and 215 resistance gene analogs
      (RGAs) were identified in the cotton expressed sequence tag database, and 347
      specific primers were developed. Meanwhile, 61 cotton genome-derived RGA markers
      and 24 resistance gene analog polymorphism (RGAP) markers from published papers
      were included to view their genomic distribution. As a result, 38 EST-derived and
      17 genome-derived RGH markers were added to our interspecific genetic map. These
      55 markers were distributed on 18 of the 26 cotton chromosomes, with 34 markers
      on 6 chromosomes (Chr03, Chr04, Chr11, Chr17, Chr19 and Chr26). Homologous RGHs
      tended to be clustered; RGH clusters appeared on 9 chromosomes, with larger
      clusters on Chr03, Chr04 and Chr19, which suggests that RGH clusters are widely
      distributed in the cotton genome. Expression analysis showed that 19 RGHs were
      significantly altered after inoculation with the V991 stain of Verticillium
      dahliae. Comparative mapping showed that four RGH markers were linked with mapped
      loci for Verticillium wilt resistance. CONCLUSIONS: The genetic mapping of RGHs
      confirmed their clustering in cotton genome. Expression analysis and comparative
      mapping suggest that EST-derived RGHs participate in cotton resistance. RGH
      markers are seemed to be useful tools to detected resistance loci and identify
      candidate resistance genes in cotton.

PMID- 25064563
TI  - The role of viral evolution in rabies host shifts and emergence.
AB  - Despite its ability to infect all mammals, Rabies virus persists in numerous
      species-specific cycles that rarely sustain transmission in alternative species.
      The determinants of these species-associations and the adaptive significance of
      genetic divergence between host-associated viruses are poorly understood. One
      explanation is that epidemiological separation between reservoirs causes neutral
      genetic differentiation. Indeed, recent studies attributed host shifts to
      ecological factors and selection of 'preadapted' viral variants from the existing
      viral community. However, phenotypic differences between isolates and broad scale
      comparative and molecular evolutionary analyses indicate multiple barriers that
      Rabies virus must overcome through adaptation. This review assesses various lines
      of evidence and proposes a synthetic hypothesis for the respective roles of
      ecology and evolution in Rabies virus host shifts. 

PMID- 25064565
TI  - img2net: automated network-based analysis of imaged phenotypes.
AB  - SUMMARY: Automated analysis of imaged phenotypes enables fast and reproducible
      quantification of biologically relevant features. Despite recent developments,
      recordings of complex networked structures, such as leaf venation patterns,
      cytoskeletal structures or traffic networks, remain challenging to analyze. Here
      we illustrate the applicability of img2net to automatedly analyze such structures
      by reconstructing the underlying network, computing relevant network properties
      and statistically comparing networks of different types or under different
      conditions. The software can be readily used for analyzing image data of
      arbitrary 2D and 3D network-like structures. AVAILABILITY AND IMPLEMENTATION:
      img2net is open-source software under the GPL and can be downloaded from
      http://mathbiol.mpimp-golm.mpg.de/img2net/, where supplementary information and
      datasets for testing are provided. CONTACT: breuer@mpimp-golm.mpg.de.

PMID- 25064564
TI  - Compression and fast retrieval of SNP data.
AB  - MOTIVATION: The increasing interest in rare genetic variants and epistatic
      genetic effects on complex phenotypic traits is currently pushing genome-wide
      association study design towards datasets of increasing size, both in the number
      of studied subjects and in the number of genotyped single nucleotide
      polymorphisms (SNPs). This, in turn, is leading to a compelling need for new
      methods for compression and fast retrieval of SNP data. RESULTS: We present a
      novel algorithm and file format for compressing and retrieving SNP data,
      specifically designed for large-scale association studies. Our algorithm is based
      on two main ideas: (i) compress linkage disequilibrium blocks in terms of
      differences with a reference SNP and (ii) compress reference SNPs exploiting
      information on their call rate and minor allele frequency. Tested on two SNP
      datasets and compared with several state-of-the-art software tools, our
      compression algorithm is shown to be competitive in terms of compression rate and
      to outperform all tools in terms of time to load compressed data. AVAILABILITY
      AND IMPLEMENTATION: Our compression and decompression algorithms are implemented
      in a C++ library, are released under the GNU General Public License and are
      freely downloadable from http://www.dei.unipd.it/~sambofra/snpack.html.

PMID- 25064566
TI  - Kotai Antibody Builder: automated high-resolution structural modeling of
      antibodies.
AB  - MOTIVATION: Kotai Antibody Builder is a Web service for tertiary structural
      modeling of antibody variable regions. It consists of three main steps: hybrid
      template selection by sequence alignment and canonical rules, 3D rendering of
      alignments and CDR-H3 loop modeling. For the last step, in addition to rule-based
      heuristics used to build the initial model, a refinement option is available that
      uses fragment assembly followed by knowledge-based scoring. Using targets from
      the Second Antibody Modeling Assessment, we demonstrate that Kotai Antibody
      Builder generates models with an overall accuracy equal to that of the best
      performing semi-automated predictors using expert knowledge. AVAILABILITY AND
      IMPLEMENTATION: Kotai Antibody Builder is available at http://kotaiab.org
      CONTACT: standley@ifrec.osaka-u.ac.jp.

PMID- 25064567
TI  - CCMpred--fast and precise prediction of protein residue-residue contacts from
      correlated mutations.
AB  - MOTIVATION: Recent breakthroughs in protein residue-residue contact prediction
      have made reliable de novo prediction of protein structures possible. The key was
      to apply statistical methods that can distinguish direct couplings between pairs
      of columns in a multiple sequence alignment from merely correlated pairs, i.e. to
      separate direct from indirect effects. Two classes of such methods exist, either
      relying on regularized inversion of the covariance matrix or on pseudo-likelihood
      maximization (PLM). Although PLM-based methods offer clearly higher precision,
      available tools are not sufficiently optimized and are written in interpreted
      languages that introduce additional overheads. This impedes the runtime and large
      scale contact prediction for larger protein families, multi-domain proteins and
      protein-protein interactions. RESULTS: Here we introduce CCMpred, our performance
      optimized PLM implementation in C and CUDA C. Using graphics cards in the price
      range of current six-core processors, CCMpred can predict contacts for typical
      alignments 35-113 times faster and with the same precision as the most accurate
      published methods. For users without a CUDA-capable graphics card, CCMpred can
      also run in a CPU mode that is still 4-14 times faster. Thanks to our speed-ups
      (http://dictionary.cambridge.org/dictionary/british/speed-up) contacts for
      typical protein families can be predicted in 15-60 s on a consumer-grade GPU and
      1-6 min on a six-core CPU. AVAILABILITY AND IMPLEMENTATION: CCMpred is free and
      open-source software under the GNU Affero General Public License v3 (or later)
      available at https://bitbucket.org/soedinglab/ccmpred.

PMID- 25064568
TI  - e-Driver: a novel method to identify protein regions driving cancer.
AB  - MOTIVATION: Most approaches used to identify cancer driver genes focus, true to
      their name, on entire genes and assume that a gene, treated as one entity, has a
      specific role in cancer. This approach may be correct to describe effects of gene
      loss or changes in gene expression; however, mutations may have different
      effects, including their relevance to cancer, depending on which region of the
      gene they affect. Except for rare and well-known exceptions, there are not enough
      data for reliable statistics for individual positions, but an intermediate level
      of analysis, between an individual position and the entire gene, may give us
      better statistics than the former and better resolution than the latter approach.
      RESULTS: We have developed e-Driver, a method that exploits the internal
      distribution of somatic missense mutations between the protein's functional
      regions (domains or intrinsically disordered regions) to find those that show a
      bias in their mutation rate as compared with other regions of the same protein,
      providing evidence of positive selection and suggesting that these proteins may
      be actual cancer drivers. We have applied e-Driver to a large cancer genome
      dataset from The Cancer Genome Atlas and compared its performance with that of
      four other methods, showing that e-Driver identifies novel candidate cancer
      drivers and, because of its increased resolution, provides deeper insights into
      the potential mechanism of cancer driver genes identified by other methods.
      AVAILABILITY AND IMPLEMENTATION: A Perl script with e-Driver and the files to
      reproduce the results described here can be downloaded from
      https://github.com/eduardporta/e-Driver.git.

PMID- 25064569
TI  - Comparison of the mammalian insulin signalling pathway to invertebrates in the
      context of FOXO-mediated ageing.
AB  - MOTIVATION: A large number of experimental studies on ageing focus on the effects
      of genetic perturbations of the insulin/insulin-like growth factor signalling
      pathway (IIS) on lifespan. Short-lived invertebrate laboratory model organisms
      are extensively used to quickly identify ageing-related genes and pathways. It is
      important to extrapolate this knowledge to longer lived mammalian organisms, such
      as mouse and eventually human, where such analyses are difficult or impossible to
      perform. Computational tools are needed to integrate and manipulate pathway
      knowledge in different species. RESULTS: We performed a literature review and
      curation of the IIS and target of rapamycin signalling pathways in Mus Musculus.
      We compare this pathway model to the equivalent models in Drosophila melanogaster
      and Caenorhabtitis elegans. Although generally well-conserved, they exhibit
      important differences. In general, the worm and mouse pathways include a larger
      number of feedback loops and interactions than the fly. We identify 'functional
      orthologues' that share similar molecular interactions, but have moderate
      sequence similarity. Finally, we incorporate the mouse model into the web-service
      NetEffects and perform in silico gene perturbations of IIS components and
      analyses of experimental results. We identify sub-paths that, given a mutation in
      an IIS component, could potentially antagonize the primary effects on ageing via
      FOXO in mouse and via SKN-1 in worm. Finally, we explore the effects of FOXO
      knockouts in three different mouse tissues. AVAILABILITY AND IMPLEMENTATION:
      http://www.ebi.ac.uk/thornton-srv/software/NetEffects.

PMID- 25064570
TI  - CCBuilder: an interactive web-based tool for building, designing and assessing
      coiled-coil protein assemblies.
AB  - MOTIVATION: The ability to accurately model protein structures at the atomistic
      level underpins efforts to understand protein folding, to engineer natural
      proteins predictably and to design proteins de novo. Homology-based methods are
      well established and produce impressive results. However, these are limited to
      structures presented by and resolved for natural proteins. Addressing this
      problem more widely and deriving truly ab initio models requires mathematical
      descriptions for protein folds; the means to decorate these with natural,
      engineered or de novo sequences; and methods to score the resulting models.
      RESULTS: We present CCBuilder, a web-based application that tackles the problem
      for a defined but large class of protein structure, the alpha-helical coiled
      coils. CCBuilder generates coiled-coil backbones, builds side chains onto these
      frameworks and provides a range of metrics to measure the quality of the models.
      Its straightforward graphical user interface provides broad functionality that
      allows users to build and assess models, in which helix geometry, coiled-coil
      architecture and topology and protein sequence can be varied rapidly. We
      demonstrate the utility of CCBuilder by assembling models for 653 coiled-coil
      structures from the PDB, which cover >96% of the known coiled-coil types, and by
      generating models for rarer and de novo coiled-coil structures. AVAILABILITY AND
      IMPLEMENTATION: CCBuilder is freely available, without registration, at
      http://coiledcoils.chm.bris.ac.uk/app/cc_builder/.

PMID- 25064572
TI  - Biocellion: accelerating computer simulation of multicellular biological system
      models.
AB  - MOTIVATION: Biological system behaviors are often the outcome of complex
      interactions among a large number of cells and their biotic and abiotic
      environment. Computational biologists attempt to understand, predict and
      manipulate biological system behavior through mathematical modeling and computer
      simulation. Discrete agent-based modeling (in combination with high-resolution
      grids to model the extracellular environment) is a popular approach for building
      biological system models. However, the computational complexity of this approach
      forces computational biologists to resort to coarser resolution approaches to
      simulate large biological systems. High-performance parallel computers have the
      potential to address the computing challenge, but writing efficient software for
      parallel computers is difficult and time-consuming. RESULTS: We have developed
      Biocellion, a high-performance software framework, to solve this computing
      challenge using parallel computers. To support a wide range of multicellular
      biological system models, Biocellion asks users to provide their model specifics
      by filling the function body of pre-defined model routines. Using Biocellion,
      modelers without parallel computing expertise can efficiently exploit parallel
      computers with less effort than writing sequential programs from scratch. We
      simulate cell sorting, microbial patterning and a bacterial system in soil
      aggregate as case studies. AVAILABILITY AND IMPLEMENTATION: Biocellion runs on
      x86 compatible systems with the 64 bit Linux operating system and is freely
      available for academic use. Visit http://biocellion.com for additional
      information.

PMID- 25064571
TI  - Big data and other challenges in the quest for orthologs.
AB  - Given the rapid increase of species with a sequenced genome, the need to identify
      orthologous genes between them has emerged as a central bioinformatics task. Many
      different methods exist for orthology detection, which makes it difficult to
      decide which one to choose for a particular application. Here, we review the
      latest developments and issues in the orthology field, and summarize the most
      recent results reported at the third 'Quest for Orthologs' meeting. We focus on
      community efforts such as the adoption of reference proteomes, standard file
      formats and benchmarking. Progress in these areas is good, and they are already
      beneficial to both orthology consumers and providers. However, a major current
      issue is that the massive increase in complete proteomes poses computational
      challenges to many of the ortholog database providers, as most orthology
      inference algorithms scale at least quadratically with the number of proteomes.
      The Quest for Orthologs consortium is an open community with a number of working
      groups that join efforts to enhance various aspects of orthology analysis, such
      as defining standard formats and datasets, documenting community resources and
      benchmarking. AVAILABILITY AND IMPLEMENTATION: All such materials are available
      at http://questfororthologs.org.

PMID- 25064574
TI  - Genetic diversity and differentiation of the Korean starry flounder (Platichthys
      stellatus) between and within cultured stocks and wild populations inferred from
      microsatellite DNA analysis.
AB  - The Korean starry flounder, Platichthys stellatus, is economically valuable
      coastal resident fish species. However, the annual catch of this fish has
      fluctuated and suffered major declines in Korea. We examined the genetic
      diversity and population structure for four wild populations and three hatchery
      stocks of Korean starry flounder to protect its genetic integrity using nine
      microsatellites. A group of 339 genotypes belonging to seven populations were
      screened. High degrees of polymorphism at the microsatellite loci were observed
      within both the wild and hatchery populations. Compared to the wild populations,
      genetic changes, including reduced genetic diversity and highly significant
      differentiation, have occurred in cultured stocks. Significant population
      differentiation was also observed in wild starry flounder populations. Similar
      degrees of inbreeding and significant Hardy-Weinberg equilibrium deviations were
      detected in both the wild and the hatchery populations. The genetic connectivity
      pattern identified four distinct metapopulations of starry flounder in Korea by
      clustering in the phylogenetic tree, Bayesian analyses, molecular variance
      analysis, PCA and multidimensional scaling analysis. A pattern of isolation-by
      distance was not significant. This genetic differentiation may be the result of
      the co-effects of various factors, such as historic dispersal, local environment
      or anthropogenic activities. These results provide useful information for the
      genetic monitoring of P. stellatus hatchery stocks, for the genetic improvement
      of this species by selective breeding and for designing suitable management
      guidelines for the conservation of this species. 

PMID- 25064573
TI  - A multicentre, pragmatic, parallel group, randomised controlled trial to compare
      the clinical and cost-effectiveness of three physiotherapy-led exercise
      interventions for knee osteoarthritis in older adults: the BEEP trial protocol
      (ISRCTN: 93634563).
AB  - BACKGROUND: Exercise is consistently recommended for older adults with knee pain
      related to osteoarthritis. However, the effects from exercise are typically small
      and short-term, likely linked to insufficient individualisation of the exercise
      programme and limited attention to supporting exercise adherence over time. The
      BEEP randomised trial aims to improve patients' short and long-term outcomes from
      exercise. It will test the overall effectiveness and cost-effectiveness of two
      physiotherapy-led exercise interventions (Individually Tailored Exercise and
      Targeted Exercise Adherence) to improve the individual tailoring of, and
      adherence to exercise, compared with usual physiotherapy care. METHODS/DESIGN:
      Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a
      multi-centre, pragmatic, parallel group, individually randomised controlled
      trial, with embedded longitudinal qualitative interviews. 500 adults in primary
      care, aged 45 years and over with knee pain will be randomised to 1 of 3
      treatment groups delivered by fully trained physiotherapists in up to 6 NHS
      services. These are: Usual Physiotherapy Care (control group consisting of up to
      4 treatment sessions of advice and exercise), Individually Tailored Exercise (an
      individualised, supervised and progressed lower-limb exercise programme) or
      Targeted Exercise Adherence (supporting patients to adhere to exercise and to
      engage in general physical activity over the longer-term). The primary outcomes
      are pain and function as measured by the Western Ontario and McMaster
      Osteoarthritis index. A comprehensive range of secondary outcomes are also
      included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and
      36 months. Data on adverse events will also be collected. Semi-structured,
      qualitative interviews with a subsample of 30 participants (10 from each
      treatment group) will be undertaken at two time-points (end of treatment and 12
      to 18 months later) and analysed thematically. DISCUSSION: This trial will
      contribute to the evidence base for management of older adults with knee pain
      attributable to osteoarthritis in primary care. The findings will have important
      implications for healthcare commissioners, general practitioners and
      physiotherapy service providers and it will inform future education of healthcare
      practitioners. It may also serve to delay or prevent some individuals from
      becoming surgical candidates. TRIAL REGISTRATION ISRCTN: ISRCTN93634563.

PMID- 25064575
TI  - Optical coherence tomography: age estimation of Calliphora vicina pupae in vivo?
AB  - Necrophagous blowfly pupae are valuable contributors to the estimation of post
      mortem interval, should an accurate age estimate be obtained. At present, this is
      reliant on a combination of rearing and destructive methods conducted on
      preserved samples, including morphological observation and gene expression
      analyses. This study demonstrates the use of optical coherence tomography (OCT)
      as a tool for in vivo morphological observation and pupal age estimation. Using a
      Michelson OCT microscope, alive and preserved four and ten-day old Calliphora
      vicina pupae were scanned in different orientations. Two and three-dimensional
      images were created. Morphological characteristics such as the brain, mouthparts
      and legs were identifiable in both living and preserved samples, with distinct
      differences noted between the two ages. Absorption of light by the puparium
      results in a vertical resolution of 1-2 mm, preventing observation of deeper
      tissues. The use of contrast agents or a longer wavelength laser would improve
      the images obtainable. At present, the data suggests OCT provides a primary view
      of external and internal morphology, which can be used to distinguish younger and
      older pupae for further analysis of age and PMI estimation.

PMID- 25064576
TI  - The clitoral body and crus size play a role in a female sexual response cycle: a
      pilot phase study: brief commentary on "Female sexual function and clitoral
      complex using MRI assessment" by Vaccoro CM et al. (Eur J Obstet Gynecol Reprod
      Biol. 2014. . doi:10.1016/j.ejogrb.2014.02.024 [Epub ahead of print]).

PMID- 25064577
TI  - Minimally conjoined monochorionic diamniotic twins - a case report.

PMID- 25064578
TI  - Canadian Cardiovascular Society guidelines for the diagnosis and management of
      stable ischemic heart disease.
AB  - This overview provides a guideline for the management of stable ischemic heart
      disease. It represents the work of a primary and secondary panel of participants
      from across Canada who achieved consensus on behalf of the Canadian
      Cardiovascular Society. The suggestions and recommendations are intended to be of
      relevance to primary care and specialist physicians with an emphasis on rational
      deployment of diagnostic tests, expedited implementation of long- and short-term
      medical therapy, timely consideration of revascularization, and practical follow
      up measures. 

PMID- 25064579
TI  - "Fishing" for the origins of the "Eskimos and heart disease" story: facts or
      wishful thinking?
AB  - During the 1970s, 2 Danish investigators, Bang and Dyerberg, on being informed
      that the Greenland Eskimos had a low prevalence of coronary artery disease (CAD)
      set out to study the diet of this population. Bang and Dyerberg described the
      "Eskimo diet" as consisting of large amounts of seal and whale blubber (ie, fats
      of animal origin) and suggested that this diet was a key factor in the alleged
      low incidence of CAD. This was the beginning of a proliferation of studies that
      focused on the cardioprotective effects of the "Eskimo diet." In view of data,
      which accumulated on this topic during the past 40 years, we conducted a review
      of published literature to examine whether mortality and morbidity due to CAD are
      indeed lower in Eskimo/Inuit populations compared with their Caucasian
      counterparts. Most studies found that the Greenland Eskimos and the Canadian and
      Alaskan Inuit have CAD as often as the non-Eskimo populations. Notably, Bang and
      Dyerberg's studies from the 1970s did not investigate the prevalence of CAD in
      this population; however, their reports are still routinely cited as evidence for
      the cardioprotective effect of the "Eskimo diet." We discuss the possible motives
      leading to the misinterpretation of these seminal studies.

PMID- 25064580
TI  - Chemotherapy-induced cardiotoxicity: detection, prevention, and management.
AB  - Chemotherapy-induced cardiotoxicity is a major cause of morbidity and mortality
      in cancer survivors. It might manifest as arrhythmia, hypertension, myocardial
      ischemia, thromboembolism, heart failure, systolic dysfunction, or other adverse
      events. Anthracyclines and trastuzumab are the chemotherapeutic agents with the
      most documented cardiac side effects; however, the array of novel molecular
      targeting therapies available is concerning because their side effects are not
      yet well understood. Nevertheless, there are potential strategies to mitigate the
      risks of cardiac complications for cancer patients. In this article, the common
      systemic drugs with cardiotoxic potential and the monitoring and diagnostic
      tools, including the role of biomarkers for early detection, are reviewed. We
      will also review the use of cardioprotectant agents as pharmacological
      interventions in prophylactic and treatment settings. Our aim is to provide a
      concise and up-to-date summary of the detection, management, and prevention of
      chemotherapy-induced cardiotoxicity for the busy clinician.

PMID- 25064581
TI  - Novel oral anticoagulants in patients with renal insufficiency: a meta-analysis
      of randomized trials.
AB  - BACKGROUND: Recent reports suggest altered antithrombotic efficacy and higher
      risk of bleeding with new oral anticoagulants (NOACs) in patients with renal
      insufficiency. A meta-analysis was performed to evaluate the efficacy and safety
      with recommended doses of NOAC compared with conventional treatment in patients
      with renal insufficiency. METHODS: PubMed, Cochrane Library, EMBASE, EBSCO, Web
      of Science, and CINAHL databases were searched from January 1, 2001 through March
      23, 2014. Randomized controlled trials that compared NOACs (rivaroxaban,
      apixaban, and dabigatran) with comparators (vitamin K antagonist/warfarin, low
      molecular weight heparin, aspirin, placebo) were selected. We defined moderate
      renal insufficiency as creatinine clearance (estimated glomerular filtration rate
      [eGFR]) of 30-49 mL/min, and mild renal insufficiency as eGFR 50-79 mL/min.
      RESULTS: There were 40,693 patients with renal insufficiency in 10 trials.
      Compared with other anticoagulants in patients with mild renal insufficiency
      there was significantly less major or clinically relevant nonmajor bleeding (odds
      ratio [OR], 0.81; 95% confidence interval [CI], 0.72-0.90) and stroke or systemic
      embolism (OR, 0.70; 95% CI, 0.54-0.92) with NOACs. Using random effects meta
      analysis, there was significantly less stroke or systemic embolism (OR, 0.72; 95%
      CI, 0.57-0.92) and a trend toward less major or clinically relevant nonmajor
      bleeding (OR, 0.82; 95% CI, 0.59-1.14) with the NOACs among patients with
      moderate renal insufficiency, and this became statistically significant when
      evaluated using a fixed effects model. NOACs showed efficiency comparable with
      conventional anticoagulants for prevention of venous thromboembolism or related
      mortality. CONCLUSIONS: In patients with renal insufficiency, recommended doses
      of novel anticoagulants are noninferior and relatively safe compared with
      conventional anticoagulants.

PMID- 25064582
TI  - Angiographic and echocardiographic correlates of suitable septal perforators for
      alcohol septal ablation in hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Myocardial contrast echocardiography during angiography is critical
      in identifying appropriate septal perforator(s) for alcohol septal ablation (ASA)
      in patients with hypertrophic obstructive cardiomyopathy. We evaluated whether
      there were other angiographic and/or echocardiographic markers that might
      identify patients who are anatomically suitable for ASA. METHODS: We performed
      quantitative coronary angiographic analysis and echocardiographic assessment on
      74 patients referred for ASA from January 2004 to July 2012 at the Peter Munk
      Cardiac Centre, University Health Network, Toronto, Ontario, Canada. Patients who
      proceeded to ASA were compared with those in whom ASA was aborted. RESULTS: Of
      the 74 patients referred for ASA, 63 proceeded to ASA and in 11 patients ASA was
      aborted because of various anatomic and technical reasons. There were no
      clinically significant differences observed in quantitative angiographic and
      echocardiographic measurements between the 2 groups. The ratio of ostial left
      main (LM) to ablated septal distance on angiography vs the basal septum to the
      septum area where the mitral valve contacted the septum because of systolic
      anterior motion (SAM) was 1.53. In the whole cohort, a significant correlation
      was observed between the ostial LM to the target septal distance and the distance
      from basal septum to SAM-septal contact point on echocardiography (r = 0.39; P =
      0.008). A stronger correlation was evident when analysis was restricted to
      patients undergoing ASA only (r = 0.44; P = 0.006). CONCLUSIONS:
      Echocardiographic and angiographic assessments of the distance between the basal
      septum to SAM-septal contact point and ostial LM to the target septal distance
      might be useful in preprocedural selection of the appropriate septal perforator
      for ASA.

PMID- 25064583
TI  - Antihypertensive medication adherence and mortality according to ethnicity: a
      cohort study.
AB  - BACKGROUND: Few studies have evaluated adherence to antihypertensive medication
      in Chinese and South Asian populations and little is known about the long-term
      outcome. Our objectives were to compare adherence to antihypertensive medications
      and assess the association of adherence and long-term mortality in Chinese, South
      Asian, and white patients with newly diagnosed hypertension. METHODS: We
      conducted a retrospective cohort study of patients with hypertension who were new
      users of antihypertensive medications (1997-2005) using administrative data and a
      province-wide prescription database from British Columbia, Canada.
      Antihypertensive medication adherence within 1 year from the date of the first
      antihypertensive drug prescription was assessed using the 'proportion of days
      covered' metric. Proportion of days covered >= 80% indicated optimal adherence.
      Patients were followed for up to 10 years for mortality. RESULTS: There were
      16,471 (11.1%) Chinese, 6099 (4.1%) South Asian, and 126,081 (84.8%) white
      patients who were prescribed antihypertensive medications. Compared with white
      patients, Chinese (odds ratio, 0.69; 95% confidence interval [CI], 0.67-0.72) and
      South Asian patients (odds ratio, 0.38; 95% CI, 0.36-0.40) were less likely to be
      optimally adherent to antihypertensive medications. Optimal adherence was
      associated with reduced mortality in white patients (risk-adjusted hazard ratio
      [aHR], 0.89; 95% CI, 0.85-0.93) but not associated with mortality in Chinese
      (aHR, 0.98; 95% CI, 0.83-1.17) and South Asian patients (aHR, 1.10; 95% CI, 0.84
      1.44). CONCLUSIONS: Chinese and South Asian patients with newly diagnosed
      hypertension were significantly less likely to adhere to antihypertensive
      medications than their white counterparts. However, optimal adherence in Chinese
      and South Asian patients was not associated with mortality.

PMID- 25064584
TI  - Trimetazidine therapy prevents obesity-induced cardiomyopathy in mice.
AB  - Obesity is a significant risk factor for the development of cardiovascular
      disease. Inhibiting fatty acid oxidation has emerged as a novel approach for the
      treatment of ischemic heart disease. Our aim was to determine whether
      pharmacologic inhibition of 3-ketoacyl-coenzyme A thiolase (3-KAT), which
      catalyzes the final step of fatty acid oxidation, could improve obesity-induced
      cardiomyopathy. A 3-week treatment with the 3-KAT inhibitor trimetazidine
      prevented obesity-induced reduction in both systolic and diastolic function.
      Therefore, targeting cardiac fatty acid oxidation may be a novel therapeutic
      approach to alleviate the growing burden of obesity-related cardiomyopathy. 

PMID- 25064585
TI  - Pan-Canadian development of cardiac rehabilitation and secondary prevention
      quality indicators.
AB  - The Canadian Cardiovascular Society (CCS) is implementing the Canadian Heart
      Health Strategy and Action Plan recommendation to build knowledge infrastructure,
      through its Data Definitions and Quality Indicator (QI) project. The CCS selected
      cardiac rehabilitation (CR) and secondary prevention as a content area for QI
      development. In accordance with the CCS QI Best Practice Methodology, rapid
      reviews of the literature were conducted. A long list of 37 QIs, in the areas of
      structure, process, and outcome were developed. Through an online survey, 26
      (42%) of all contacted external experts rated each QI on importance, scientific
      acceptability, and feasibility, using a 7-point scale. The overall mean rating
      was 5.4 +/- 1.4. Through a consensus process, the working group excluded 8 QIs
      based on this feedback, and several others were revised. A 30-day Web
      consultation was then undertaken, to solicit input from the broader CCS and CR
      community. A "top 5" list of QIs was requested by the CCS, which were: (1)
      inpatients referred to CR; (2) wait times from referral to CR enrollment; (3)
      patient self-management education; (4) increase in exercise capacity; and (5)
      emergency response strategy. Knowledge translation activities are now under way
      to promote utilization of the QIs and ultimately improve CR care.

PMID- 25064586
TI  - Reply to Letter From Wallace et al.-Septal Perforator Size May Play a Key Role in
      Alcohol Septal Ablation Success.

PMID- 25064587
TI  - Current status of molecular biomarkers in endometrial cancer.
AB  - In spite of the high and increasing incidence of endometrial cancer, our current
      models for prediction of prognosis and even more treatment response are
      suboptimal, and molecular biomarkers to assist clinical decision making are
      needed. In this review an overview is given of the currently known as well as
      promising prognostic and predictive biomarkers in endometrial carcinoma. Key
      clinical challenges, where use of molecular biomarkers can meet clinical needs,
      are highlighted. The current status for the presently most promising prognostic
      and predictive biomarkers in endometrial carcinoma is reviewed. DNA ploidy, p53
      status, hormone receptor level, HER2, stathmin, L1 cell adhesion molecule
      expression and other biomarkers are discussed in relation to the scientific
      robustness of various essential steps in biomarker development and (current)
      clinical applicability for individualizing treatment strategies. Tumour
      heterogeneity and its consequences for biomarker assessment and the importance of
      developing standardised tests for implementation are discussed. To improve the
      development and clinical uptake of biomarkers, several strategies are proposed. 

PMID- 25064588
TI  - Oligomerization of Cysteine String Protein alpha mutants causing adult neuronal
      ceroid lipofuscinosis.
AB  - Cysteine String Protein alpha (CSPalpha) is a palmitoylated, synaptic vesicle co
      chaperone that is essential for neuroprotection. Two mutations in CSPalpha -
      L115R and L116Delta - cause adult neuronal ceroid lipofuscinosis (ANCL), a
      dominantly-inherited neurodegenerative disease. To elucidate the pathogenesis of
      ANCL, the intrinsic biochemical properties of human wildtype (WT) and disease
      mutant CSPalpha were examined. Mutant proteins purified from Escherichia coli
      exhibited high potency to oligomerize in a concentration, temperature, and time
      dependent manner, with L115R possessing the greatest potency. When freshly
      purified, ANCL mutant proteins displayed normal co-chaperone activity and
      substrate recognition similar to WT. However, co-chaperone activity was impaired
      for both CSPalpha mutants upon oligomerization. When WT and mutant CSPalpha were
      mixed together they co-oligomerized leading to an overall decrease of co
      chaperone activity. The oligomerization properties of ANCL mutants were
      faithfully replicated in HEK 293T cells. Interestingly, the oligomers were
      covalently tagged by ubiquitination instead of palmitoylation. Taken together,
      ANCL mutations result in both a gain and partial loss-of-function. 

PMID- 25064589
TI  - The role of soluble adenylyl cyclase in neurite outgrowth.
AB  - Axon regeneration in the mature central nervous system is limited by extrinsic
      inhibitory signals and a postnatal decline in neurons' intrinsic growth capacity.
      Neuronal levels of the second messenger cAMP are important in regulating both
      intrinsic growth capacity and neurons' responses to extrinsic factors. Approaches
      which increase intracellular cAMP in neurons enhance neurite outgrowth and
      facilitate regeneration after injury. Thus, understanding the factors which
      affect cAMP in neurons is of potential therapeutic importance. Recently, soluble
      adenylyl cyclase (sAC, ADCY10), the ubiquitous, non-transmembrane adenylyl
      cyclase, was found to play a key role in neuronal survival and axon growth. sAC
      is activated by bicarbonate and cations and may translate physiologic signals
      from metabolism and electrical activity into a neuron's decision to survive or
      regenerate. Here we critically review the literature surrounding sAC and cAMP
      signaling in neurons to further elucidate the potential role of sAC signaling in
      neurite outgrowth and regeneration. This article is part of a Special Issue
      entitled: The role of soluble adenylyl cyclase in health and disease. 

PMID- 25064590
TI  - Soluble adenylyl cyclase of sea urchin spermatozoa.
AB  - Fertilization, a key step in sexual reproduction, requires orchestrated changes
      in cAMP concentrations. It is notable that spermatozoa (sperm) are among the cell
      types with extremely high adenylyl cyclase (AC) activity. As production and
      consumption of this second messenger need to be locally regulated, the discovery
      of soluble AC (sAC) has broadened our understanding of how such cells deal with
      these requirements. In addition, because sAC is directly regulated by HCO(3)(-)
      it is able to translate CO2/HCO(3)(-)/pH changes into cAMP levels. Fundamental
      sperm functions such as maturation, motility regulation and the acrosome reaction
      are influenced by cAMP; this is especially true for sperm of the sea urchin (SU),
      an organism that has been a model in the study of fertilization for more than 130
      years. Here we summarize the discovery and properties of SU sperm sAC, and
      discuss its involvement in sperm physiology. This article is part of a Special
      Issue entitled: The role of soluble adenylyl cyclase in health and disease.

PMID- 25064592
TI  - An open letter for the people in Gaza.

PMID- 25064591
TI  - Soluble adenylyl cyclase in health and disease.
AB  - The second messenger cAMP is integral for many physiological processes. Soluble
      adenylyl cyclase (sAC) was recently identified as a widely expressed
      intracellular source of cAMP in mammalian cells. sAC is evolutionary,
      structurally, and biochemically distinct from the G-protein-responsive
      transmembranous adenylyl cyclases (tmAC). The structure of the catalytic unit of
      sAC is similar to tmAC, but sAC does not contain transmembranous domains,
      allowing localizations independent of the membranous compartment. sAC activity is
      stimulated by HCO(3)(-), Ca2+ and is sensitive to physiologically relevant ATP
      fluctuations. sAC functions as a physiological sensor for carbon dioxide and
      bicarbonate, and therefore indirectly for pH. Here we review the physiological
      role of sAC in different human tissues with a major focus on the lung. This
      article is part of a Special Issue entitled: The role of soluble adenylyl cyclase
      in health and disease, guest edited by J. Buck and L.R. Levin.

PMID- 25064593
TI  - How to hinder tuberculosis control: five easy steps.

PMID- 25064594
TI  - Efficacy of paracetamol for acute low-back pain: a double-blind, randomised
      controlled trial.
AB  - BACKGROUND: Regular paracetamol is the recommended first-line analgesic for acute
      low-back pain; however, no high-quality evidence supports this recommendation. We
      aimed to assess the efficacy of paracetamol taken regularly or as-needed to
      improve time to recovery from pain, compared with placebo, in patients with low
      back pain. METHODS: We did a multicentre, double-dummy, randomised, placebo
      controlled trial across 235 primary care centres in Sydney, Australia, from Nov
      11, 2009, to March 5, 2013. We randomly allocated patients with acute low-back
      pain in a 1:1:1 ratio to receive up to 4 weeks of regular doses of paracetamol
      (three times per day; equivalent to 3990 mg paracetamol per day), as-needed doses
      of paracetamol (taken when needed for pain relief; maximum 4000 mg paracetamol
      per day), or placebo. Randomisation was done according to a centralised
      randomisation schedule prepared by a researcher who was not involved in patient
      recruitment or data collection. Patients and staff at all sites were masked to
      treatment allocation. All participants received best-evidence advice and were
      followed up for 3 months. The primary outcome was time until recovery from low
      back pain, with recovery defined as a pain score of 0 or 1 (on a 0-10 pain scale)
      sustained for 7 consecutive days. All data were analysed by intention to treat.
      This study is registered with the Australian and New Zealand Clinical Trial
      Registry, number ACTN 12609000966291. FINDINGS: 550 participants were assigned to
      the regular group (550 analysed), 549 were assigned to the as-needed group (546
      analysed), and 553 were assigned to the placebo group (547 analysed). Median time
      to recovery was 17 days (95% CI 14-19) in the regular group, 17 days (15-20) in
      the as-needed group, and 16 days (14-20) in the placebo group (regular vs placebo
      hazard ratio 0.99, 95% CI 0.87-1.14; as-needed vs placebo 1.05, 0.92-1.19;
      regular vs as-needed 1.05, 0.92-1.20). We recorded no difference between
      treatment groups for time to recovery (adjusted p=0.79). Adherence to regular
      tablets (median tablets consumed per participant per day of maximum 6; 4.0 [IQR
      1.6-5.7] in the regular group, 3.9 [1.5-5.6] in the as-needed group, and 4.0 [1.5
      5.7] in the placebo group), and number of participants reporting adverse events
      (99 [18.5%] in the regular group, 99 [18.7%] in the as-needed group, and 98
      [18.5%] in the placebo group) were similar between groups. INTERPRETATION: Our
      findings suggest that regular or as-needed dosing with paracetamol does not
      affect recovery time compared with placebo in low-back pain, and question the
      universal endorsement of paracetamol in this patient group. FUNDING: National
      Health and Medical Research Council of Australia and GlaxoSmithKline Australia.

PMID- 25064595
TI  - Do patients with acute low-back pain need paracetamol?

PMID- 25064596
TI  - Morphological and molecular data reveal a new species of Neoechinorhynchus
      (Acanthocephala: Neoechinorhynchidae) from Dormitator maculatus in the Gulf of
      Mexico.
AB  - Neoechinorhynchus (Neoechinorhynchus) mexicoensis sp. n. is described from the
      intestine of Dormitator maculatus (Bloch 1792) collected in 5 coastal localities
      from the Gulf of Mexico. The new species is mainly distinguished from the other
      33 described species of Neoechinorhynchus from the Americas associated with
      freshwater, marine and brackish fishes by having smaller middle and posterior
      hooks and possessing a small proboscis with three rows of six hooks each, apical
      hooks longer than other hooks and extending to the same level as the posterior
      hooks, 1 giant nucleus in the ventral body wall and females with eggs longer than
      other congeneric species. Sequences of the internal transcribed spacer (ITS) and
      the large subunit (LSU) of ribosomal DNA including the domain D2+D3 were used
      independently to corroborate the morphological distinction among the new species
      and other congeneric species associated with freshwater and brackish water fish
      from Mexico. The genetic divergence estimated among congeneric species ranged
      from 7.34 to 44% for ITS and from 1.65 to 32.9% for LSU. Maximum likelihood and
      Bayesian inference analyses with each dataset showed that the 25 specimens
      analyzed from 5 localities of the coast of the Gulf of Mexico parasitizing D.
      maculatus represent an independent clade with strong bootstrap support and
      posterior probabilities. The morphological evidence, plus the monophyly in the
      phylogenetic analyses, indicates that the acanthocephalans collected from
      intestine of D. maculatus from the Gulf of Mexico represent a new species, herein
      named N. (N.) mexicoensis sp. n. 

PMID- 25064597
TI  - Water deficit down-regulates miR398 and miR408 in pea (Pisum sativum L.).
AB  - MicroRNAs (miRNAs), recently recognized as important regulator of gene expression
      at posttranscriptional level, have been found to be involved in plant stress
      responses. The observation that some miRNAs are up- or down regulated by stress
      implies that they could play vital roles in plant resistance to abiotic and
      biotic stress. We investigated the effect of water stress treatment during 10
      days on expression of conserved miRNAs-miR398a/b and miR408 in pea plants. This
      time frame reflects the changes as close as possible to the changes where water
      stress causes visible effects under field condition. It was observed that
      dehydration strongly down regulates the expression of both miR398a/b and miR408
      in pea roots and shoots. The down-regulation of miR398a/b and the up-regulation
      of potential target genes - copper superoxide dismutase, CSD1, highlight the
      involvement of this miRNA in pea stress response. To the contrary, the mRNA level
      of cytochrome c oxidase subunit 5 (COX5b) did not change in roots and shoots of
      water-stressed plants, compared to control (well) hydrated plants. This suggests
      that COX5b is not the target of miR398, or that its expression is regulated by
      some other mechanism. P1B-ATPase expression increased during water deficit only
      in the shoots of pea; in the roots there were no changes in expression. Our
      results help to understand the possible role of investigated miRNAs and their
      contribution to pea capacity to cope with water deficit. 

PMID- 25064598
TI  - Use of elemental and molecular-mass spectrometry to assess the toxicological
      effects of inorganic mercury in the mouse Mus musculus.
AB  - The biochemical response of mice (Mus musculus) to acute subcutaneous inorganic
      mercury exposure was assessed over a 14-day period by analyzing cytosolic
      extracts of the liver, the kidneys, and blood plasma. Integrated metallomic and
      metabolomic approaches using elemental and molecular-mass spectrometry were used
      to obtain comprehensive insight into the toxicological effects of mercury
      regarding its distribution and possible perturbation of metabolic pathways. The
      metallomic approach involved the use of size-exclusion chromatography (SEC)
      coupled with multiaffinity chromatography inductively coupled plasma-mass
      spectrometry (ICP-MS) and isotopic-dilution analysis. The metabolomic approach
      involved the direct infusion of polar and lipophilic tissue extracts into a mass
      spectrometer (DIMS) in the positive and negative acquisition mode (ESI+and ESI-).
      The use of SEC-ICP-MS enabled us to detect changes in the metalloproteome in the
      liver and the kidneys during the exposure period, and revealed that interactions
      between Hg and endogenous Cu and Zn adversely affected the homeostasis of these
      essential metals. The detection of an Hg-Se detoxification product in mouse
      plasma substantiated the known interaction between Hg and Se in mammals. Use of
      DIMS in conjunction with partial-least-squares discriminant analysis (PLS-DA)
      uncovered time-dependent changes of endogenous metabolites over time,
      corroborated by histopathology investigation of specific mouse tissues. The
      perturbations of endogenous metabolic profiles were explained in terms of the
      adverse effect of mercury on energy metabolism (e.g. glycolysis, Krebs cycle),
      the degradation of membrane phospholipids (apoptosis), and increased levels of
      specific lipids in plasma. In summary, use of an SEC-ICP-MS-based metallomics
      approach in conjunction with molecular-mass-spectrometry-based metabolomics is
      revealed as a promising strategy to more comprehensively investigate the
      toxicological effects of harmful environmental pollutants and xenobiotics. 

PMID- 25064599
TI  - Detection of conformation types of cyclosporin retaining intramolecular hydrogen
      bonds by mass spectrometry.
AB  - Cyclosporin is a family of neutral cyclic undecapeptides widely used for the
      prevention of organ transplant rejection and controlling viral infection. The
      equilibrium of conformations assumed by cyclosporin A in response to the solvent
      environment is thought to play a critical role in enabling good membrane
      penetration, which improves upon shielding the polarity of the molecule through
      forming intramolecular hydrogen bonds. However, the distribution of structures
      and their internal hydrogen bond geometries have not been elucidated thus far
      across the series of cyclosporins. Herein, we elucidate the conformational
      heterogeneity of cyclosporins using a set of analytical approaches including ion
      mobility mass spectrometry, hydrogen-deuterium exchange, and molecular dynamics
      simulation. Ion mobility measurements reveal a specific conformational
      distribution for each cyclosporin derivative in a structure-dependent manner. In
      general, we observe that the more compact conformer is associated with a greater
      frequency of intramolecular hydrogen bonds. Cyclosporin A is populated by
      structures with an extensive hydrogen bond network that is lacking in cyclosporin
      H, which is composed predominantly of a single compact conformation. The slower
      dynamics of cyclosporin H backbone is also consistent with the lack of hydrogen
      bonds. Furthermore, we find a strong correlation between the steric bulk of the
      side chain at position 2 of cyclosporin and the distribution of conformers due to
      differential accommodation of side chains within the macrocycle, and also report
      a wide range of conformational dynamics in solution. 

PMID- 25064601
TI  - Evaluation of detection sensitivity in comprehensive two-dimensional liquid
      chromatography separations of an active pharmaceutical ingredient and its
      degradants.
AB  - In this paper, we describe the findings of a study aimed at assessing the
      detection sensitivity of comprehensive two-dimensional high-performance liquid
      chromatography (LCxLC) separation of a degraded active pharmaceutical ingredient
      (API) with UV absorption as the detection technique. Specifically, we have
      examined the impact of the volume and solvent composition (referred to as
      "interface conditions") of fractions of first-dimension column effluent
      transferred to the second dimension for further separation on the ability to
      resolve and detect low-abundance compounds. Historically, LCxLC has been
      perceived as being inferior to 1D-LC from the point of view of detection
      sensitivity. In this work, we demonstrate that LCxLC is sufficiently sensitive to
      be useful in the pharmaceutical context where in general impurities present at
      0.05 % (relative to the API concentration) should be quantified. Moreover, we
      find that this level of sensitivity is only attained under certain conditions:
      dilution of the first column effluent with weak solvent (water in this case)
      prior to injection into the second-dimension column is very beneficial because it
      promotes focusing of the analyte band in the second column, thereby improving the
      detection sensitivity of the LCxLC system; and, quantitation limits are also a
      strong function of peak location in the second-dimension separation window, where
      baseline disturbances near the dead time of the second column can limit reliable
      detection of low-abundance compounds. 

PMID- 25064600
TI  - Biosynthesis of 15N-labeled cylindrospermopsin and its application as internal
      standard in stable isotope dilution analysis.
AB  - Cylindrospermopsin (CYN) is a cyanobacterial toxin associated with human and
      animal poisonings. Due to its toxicity in combination with its widespread
      occurrence, the development of reliable methods for selective, sensitive
      detection and accurate quantification is mandatory. Liquid chromatography tandem
      mass spectrometry (LC-MS/MS) analysis using stable isotope dilution analysis
      (SIDA) represents an ideal tool for this purpose. U-[(15)N5]-CYN was synthesized
      by culturing Aphanizomenon flos-aquae in Na(15)NO3-containing cyanobacteria
      growth medium followed by a cleanup using graphitized carbon black columns and
      mass spectrometric characterization. Subsequently, a SIDA-LC-MS/MS method for the
      quantification of CYN in freshwater and Brassica matrices was developed showing
      satisfactory performance data. The recovery ranged between 98 and 103 %; the
      limit of quantification was 15 ng/L in freshwater and 50 MUg/kg dry weight in
      Brassica samples. The novel SIDA was applied for CYN determination in real
      freshwater samples as well as in kale and in vegetable mustard exposed to toxin
      containing irrigation water. Two of the freshwater samples taken from German
      lakes were found to be CYN-contaminated above limit of quantification (17.9 and
      60.8 ng/L). CYN is systemically available to the examined vegetable species after
      exposure of the rootstock leading to CYN mass fractions in kale and vegetable
      mustard leaves of 15.0 MUg/kg fresh weight and 23.9 MUg/kg fresh weight,
      respectively. CYN measurements in both matrices are exemplary for the versatile
      applicability of the developed method in environmental analysis. 

PMID- 25064602
TI  - Diabetes induces changes in KIF1A, KIF5B and dynein distribution in the rat
      retina: implications for axonal transport.
AB  - Diabetic retinopathy is a leading cause of vision loss and blindness. Disruption
      of axonal transport is associated with many neurodegenerative diseases and might
      also play a role in diabetes-associated disorders affecting nervous system. We
      investigated the impact of type 1 diabetes (2 and 8 weeks duration) on KIF1A,
      KIF5B and dynein motor proteins in the retina. Additionally, since hyperglycemia
      is considered the main trigger of diabetic complications, we investigated whether
      prolonged exposure to elevated glucose could affect the content and distribution
      of motor proteins in retinal cultures. The immunoreactivity of motor proteins was
      evaluated by immunohistochemistry in retinal sections and by immunoblotting in
      total retinal extracts from streptozotocin-induced diabetic and age-matched
      control animals. Primary retinal cultures were exposed to high glucose (30 mM) or
      mannitol (osmotic control; 24.5 mM plus 5.5 mM glucose), for seven days. Diabetes
      decreased the content of KIF1A at 8 weeks of diabetes as well as KIF1A
      immunoreactivity in the majority of retinal layers, except for the photoreceptor
      and outer nuclear layer. Changes in KIF5B immunoreactivity were also detected by
      immunohistochemistry in the retina at 8 weeks of diabetes, being increased at the
      photoreceptor and outer nuclear layer, and decreased in the ganglion cell layer.
      Regarding dynein immunoreactivity there was an increase in the ganglion cell
      layer after 8 weeks of diabetes. No changes were detected in retinal cultures.
      These alterations suggest that axonal transport may be impaired under diabetes,
      which might contribute to early signs of neural dysfunction in the retina of
      diabetic patients and animal models. 

PMID- 25064603
TI  - Acetylation: a lysine modification with neuroprotective effects in ischemic
      retinal degeneration.
AB  - Neuroretinal ischemic injury contributes to several degenerative diseases in the
      eye and the resulting pathogenic processes involving a series of necrotic and
      apoptotic events. This study investigates the time and extent of changes in
      acetylation, and whether this influences function and survival of neuroretinal
      cells following injury. Studies evaluated the time course of changes in histone
      deacetylase (HDAC) activity, histone-H3 acetylation and caspase-3 activation
      levels as well as retinal morphology and function (electroretinography) following
      ischemia. In addition, the effect of two HDAC inhibitors, trichostatin-A and
      valproic acid were also investigated. In normal eyes, retinal ischemia produced a
      significant increase in HDAC activity within 2 h that was followed by a
      corresponding significant decrease in protein acetylation by 4 h. Activated
      caspase-3 levels were significantly elevated by 24 h. Treatment with HDAC
      inhibitors blocked the early decrease in protein acetylation and activation of
      caspase-3. Retinal immunohistochemistry demonstrated that systemic administration
      of trichostatin-A or valproic acid, resulted in hyperacetylation of all retinal
      layers after systemic treatment. In addition, HDAC inhibitors provided a
      significant functional and structural neuroprotection at seven days following
      injury relative to vehicle-treated eyes. These results provide evidence that
      increases in HDAC activity is an early event following retinal ischemia, and are
      accompanied by corresponding decreases in acetylation in advance of caspase-3
      activation. In addition to preserving acetylation status, the administration of
      HDAC inhibitors suppressed caspase activation and provided structural and
      functional neuroprotection in model of ischemic retinal injury. Taken together
      these data provide evidence that decrease in retinal acetylation status is a
      central event in ischemic retinal injury, and the hyperacetylation induced by
      HDAC inhibition can provide acute neuroprotection. 

PMID- 25064604
TI  - Beta-blocker timolol alleviates hyperglycemia-induced cardiac damage via
      inhibition of endoplasmic reticulum stress.
AB  - Current data support that pharmacological modulators of endoplasmic reticulum
      stress (ERS) have therapeutic potential for diabetic individuals. Therefore, we
      aimed to examine whether timolol, having free radical-scavenger action, besides
      being a beta-blocker, exerts a cardioprotective effect via inhibition of ERS
      response in diabetic rats in a comparison with an antioxidant N-acetylcysteine
      (NAC). Histopathological data showed that either timolol- or NAC-treatment of
      diabetic rats prevented the changes in mitochondria and nucleus of the cardiac
      tissue while they enhanced the cellular redox-state in heart as well. The levels
      of ER-targeted cytoprotective chaperones GRP78 and calnexin, unfolded protein
      response signaling protein CHO/Gadd153 besides the levels of calpain, BCL-2,
      phospho-Akt, PUMA, and PML in the hearts from diabetic rats, treated with either
      timolol or NAC, are found to be similar among these groups, although all these
      parameters were markedly preserved in the untreated diabetics compared to those
      of the controls. Taken into consideration how important a balanced-ratio between
      anti-apoptotic and pro-apoptotic proteins for the maintenance mitochondria/ER
      function, our results suggest that ERS in diabetic rat heart is mediated by
      increased oxidative damage, which in turn triggers cardiac dysfunction. Moreover,
      we also demonstrated that timolol treatment of diabetic rats, similar to NAC
      treatment, induced a well-controlled redox-state and apoptosis in cardiac
      myocardium. We, thus for the first time, report that cardioprotective effect of
      timolol seems to be associated with normalization of ER function due to its
      antioxidant action in cardiomyocytes even under hyperglycemia. 

PMID- 25064605
TI  - Digital report in an anatomy laboratory: a new method for team-based dissection,
      reporting, and evaluation.
AB  - PURPOSE: Digital report (DR), a new method for students' dissection report, has
      been introduced to replace the traditional method in the anatomy laboratory.
      METHODS: Laboratory tasks were assigned to groups of five students, and each
      group was asked to make a DR of their dissection tasks and upload it on the
      website for the anatomy course developed by the authors' institution. For
      creating the DR, students were instructed to take photographs of their findings
      with digital cameras, to mark the orientation and label the structures on the
      photograph. Students were assessed as a group by evaluating the DR. All the
      photographs of the DR were saved to construct a database that can be used by the
      students who will take the anatomy course in the following years. A questionnaire
      consisting of 14 questions was administered at the end of the anatomy course to
      evaluate the effectiveness of the DR. RESULTS: The results of the student survey
      showed that the DR was useful for making the students participate more actively
      in the teamwork for dissection, and for making dissection reports by referring to
      the DR made by the students from previous years. The DR was also more helpful for
      the anatomy teacher to assess student learning in the anatomy laboratory than
      conventional practical examinations and paper-based dissection reports.
      CONCLUSIONS: DR, a paperless report of team-based dissection, is concurrent with
      the 'digital' age and is in line with the need for a more systematic and
      objective evaluation of students' dissection.

PMID- 25064606
TI  - The role of PfEMP1 adhesion domain classification in Plasmodium falciparum
      pathogenesis research.
AB  - The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family has a
      key role in parasite survival, transmission, and virulence. PfEMP1 are exported
      to the erythrocyte membrane and mediate binding of infected erythrocytes to the
      endothelial lining of blood vessels. This process aids parasite survival by
      avoiding spleen-dependent killing mechanisms, but it is associated with adhesion
      based disease complications. Switching between PfEMP1 proteins enables parasites
      to evade host immunity and modifies parasite tropism for different microvascular
      beds. The PfEMP1 protein family is one of the most diverse adhesion modules in
      nature. This review covers PfEMP1 adhesion domain classification and the
      significant role it is playing in deciphering and deconvoluting P. falciparum
      cytoadhesion and disease. 

PMID- 25064607
TI  - Tb927.10.6900 encodes the glucosyltransferase involved in synthesis of base J in
      Trypanosoma brucei.
AB  - Base J is a DNA modification found in the genome of Trypanosoma brucei and all
      other kinetoplastids analyzed, where it replaces a small fraction of Ts, mainly
      in telomeric and chromosome-internal transcription initiation and termination
      regions. The synthesis of base J is a two-step process whereby a specific T is
      converted to HOMedU (hydroxymethyldeoxyuridine) and subsequently glucosylated to
      generate J. The thymidine hydroxylases (JPB1 and JBP2) that catalyze the first
      step have been characterized, but the identity of the glucosyltransferase
      catalyzing the second step has proven elusive. Recent bioinformatic analysis by
      Iyer et al. (Nucleic Acids Res 2013;41:7635) suggested that Tb927.10.6900 encodes
      the glucosyltransferase (HmdUGT) responsible for converting HOMedU to J in T.
      brucei. We now present experimental evidence to validate this hypothesis; null
      mutants of Tb927.10.6900 are unable to synthesize base J. Orthologues from
      related kinetoplastids show only modest conservation, with several insertion
      sequences found in those from Leishmania and related genera. 

PMID- 25064608
TI  - Induction of hepatoma carcinoma cell apoptosis through activation of the JNK
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-ROS self-driven death
      signal circuit.
AB  - As an efficient method for inducing tumor cell apoptosis, ROS can be constantly
      formed and accumulated in NADPH oxidase overactivated-cells, resulting in further
      mitochondrial membrane damage and mitochondria-dependent apoptosis. In addition,
      JNK mitogen-activated protein kinase (JNK MAPK) signal also acts as a vital
      candidate pathway for inducing tumor cell apoptosis by targeting mitochondrial
      death pathway. However, the relationship between NADPH oxidase-ROS and JNK MAPK
      signal still remains unclear. Here, we discovered a novel self-driven signal
      circuit between NADPH oxidase-ROS and JNK MAPK, which was induced by a cytotoxic
      steroidal saponin (ASC) in hepatoma carcinoma cells. NADPH oxidase-dependent ROS
      production was markedly activated by ASC and directly led to JNK MAPK activation.
      Moreover, antioxidant, NADPH oxidase inhibitor and specific knock-out for p47
      subunit of NADPH oxidase could effectively block NADPH oxidase-ROS-dependent JNK
      activation, suggesting that NADPH oxidase is an upstream regulator of JNK MAPK.
      Conversely, a specific JNK inhibitor could inhibit ASC-induced NADPH oxidase
      activation and down-regulate ROS levels as well, indicating that JNK might also
      regulate NADPH oxidase activity to some extent. These observations indicate that
      NADPH oxidase and JNK MAPK activate each other as a signal circuit. Furthermore,
      drug pretreatment experiments with ASC showed this signal circuit operated
      continuously via a self-driven mode and finally induced apoptosis in hepatoma
      carcinoma cells. Taken together, we provide a proof for inducing hepatoma
      carcinoma cell apoptosis by activating the JNK-NADPH oxidase-ROS-dependent self
      driven signal circuit pathway. 

PMID- 25064609
TI  - Desmoid-type fibromatosis-associated Gardner fibromas: prevalence and impact on
      local recurrence.
AB  - Although Gardner fibroma is a precursor lesion of desmoid tumor, the prevalence
      and prognostic importance of Gardner fibroma associated with desmoid tumors has
      not been systematically studied in adults. From 129 patients with desmoid-type
      fibromatosis, 170 specimens were re-examined for the presence of an associated
      Gardner fibroma. Clinicopathologic features of Gardner fibroma-associated desmoid
      type fibromatosis were compared to desmoid tumors without associated Gardner
      fibroma. Recurrence-free survival was compared using multivariate Cox
      proportional hazard regression to account for known confounding factors. Of 104
      evaluable primary desmoid tumor resections, 25 (24%) had an associated Gardner
      fibroma. When previous incisional biopsies and resection specimens of locally
      recurrent desmoid tumors were also examined, the overall prevalence of associated
      Gardner fibroma was 37%. Desmoid tumors arising in high risk anatomic sites
      (extremities or deep soft tissues of the back and chest wall) were more often
      associated with Gardner fibroma than tumors at other sites. Median recurrence
      free survival for patients with Gardner fibroma-associated desmoid-type
      fibromatosis was 3.2 years, whereas median survival for patients without
      associated Gardner fibroma was >25 years (hazard ratio 2.8; P = 0.001). Although
      the presence of Gardner fibroma had no impact on the recurrence rate of desmoid
      tumors arising at high risk anatomic sites, associated Gardner fibroma increased
      the risk of recurrence 4-fold for desmoid tumors at low risk anatomic sites.
      Associated Gardner fibroma is under-recognized in desmoid-type fibromatosis and
      increases the risk of local recurrence for a subgroup of patients. 

PMID- 25064610
TI  - Vaccination against infectious diseases: what is promising?
AB  - Vaccination has proven to be one of the best weapons protecting the mankind
      against infectious diseases. Along with the huge progress in microbiology,
      numerous highly efficacious and safe vaccines have been produced by conventional
      technology (cultivation), by the use of molecular biology (genetic modification),
      or by synthetic chemistry. Sterilising prevention is achieved by the stimulation
      of antibody production, while the stimulation of cell-mediated immune responses
      may prevent the outbreak of disease in consequence of an acute or reactivated
      infection. From several examples, two rules are deduced to evaluate the
      perspectives of future vaccine developments: They are promising, if (1) the
      natural infectious disease induces immunity or (2) passive immunisation (transfer
      of antibodies, adoptive transfer of lymphocytes) is successful in preventing
      infection. 

PMID- 25064611
TI  - Is hyperuricemia an independent risk factor for new-onset chronic kidney
      disease?: A systematic review and meta-analysis based on observational cohort
      studies.
AB  - BACKGROUND: Hyperuricemia has been reported to be associated with chronic kidney
      disease (CKD). However whether an elevated serum uric acid level is an
      independent risk factor for new-onset CKD remained controversial. METHODS: A
      systematic review and meta-analysis using a literature search of online databases
      including PubMed, Embase, Ovid and ISI Web/Web of Science was conducted. Summary
      adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were
      calculated to evaluate the risk estimates of hyperuricemia for new-onset CKD.
      RESULTS: Thirteen studies containing 190,718 participants were included. A
      significant positive association was found between elevated serum uric acid
      levels and new-onset CKD at follow-up (summary OR, 1.15; 95% CI, 1.05-1.25).
      Hyperuricemia was found be an independent predictor for the development of newly
      diagnosed CKD in non-CKD patients (summary OR, 2.35; 95% CI, 1.59-3.46). This
      association increased with increasing length of follow-up. No significant
      differences were found for risk estimates of the associations between elevated
      serum uric acid levels and developing CKD between males and females. CONCLUSIONS:
      With long-term follow-up of non-CKD individuals, elevated serum uric acid levels
      showed an increased risk for the development of chronic renal dysfunction.

PMID- 25064612
TI  - Recovery of soil nitrification after long-term zinc exposure and its co-tolerance
      to Cu in different soils.
AB  - Soils sampled from different locations of China were used to manipulate soil
      microbial diversity and to assess the effect of the diversity of the soil
      nitrifying community on the recovery of the soil nitrification to metal stress
      (zinc). Ten treatments were either or not amended with ZnCl2. Subsequently, a
      spike-on-spike assay was set up to test for the tolerance of soil nitrification
      to zinc (Zn) and copper (Cu). Initially, Zn amendment completely inhibited
      nitrification. After a year of Zn exposure, recovery of the potential
      nitrification rate in Zn-amended soils ranged from 28 to 126% of the potential
      nitrification rate in the corresponding Zn-nonamended soils. This recovery was
      strongly related to the potential nitrification rate before Zn amendment and soil
      pH. Increased Zn tolerance of the soil nitrification was consistently observed in
      response to corresponding soil contamination. Co-tolerance to Cu was obtained in
      all 1,000-mg kg(-1) Zn-amended soils. This tolerance was also strongly related to
      the potential nitrification rate before Zn amendment and soil pH. Our data
      indicate that inherently microbial activity can be a significant factor for the
      recovery of soil functioning derived from metal contamination.

PMID- 25064614
TI  - The challenge of artemisinin resistance can only be met by eliminating Plasmodium
      falciparum malaria across the Greater Mekong subregion.
AB  - Artemisinin-based combinations are currently the most effective anti-malarials
      and, in addition to vector control, have led to significant declines in malaria
      morbidity and mortality. However, foci of artemisinin drug resistance have been
      identified in the Greater Mekong subregion (GMS) of the Asia Pacific, threatening
      the major gains made in malaria control and potentially creating a parasite pool
      that is more difficult to treat and eliminate. Efforts are underway to halt the
      spread of artemisinin resistance, including coordination of activities and
      funding, and identification of areas of suspected artemisinin resistance, now
      using a newly identified molecular marker. However, targeting resources to the
      containment of resistant parasites is likely inefficient and monitoring impact is
      challenging. A more sustainable solution is the rapid elimination of all
      Plasmodium falciparum parasites from the GMS. This strategy is more efficient for
      several reasons. First, a subregional strategy is in line with current commitment
      to elimination and will build upon the existing national political support for
      elimination as well as enhancing collaboration among countries. Second, the
      challenge of human mobility in the GMS is subregional in scope and requires a
      harmonized elimination strategy. Third, countries will need to improve and
      intensify malaria operations to reach elimination, and this will be a singular
      goal across the subregion. Rallying around the goal of P. falciparum elimination
      will not only utilize existing regional bodies to catalyze political and funding
      support, but will also leverage the funding already in place to achieve this
      subregional goal. 

PMID- 25064613
TI  - Association between the XRCC1 Arg194Trp polymorphism and risk of cancer: evidence
      from 201 case-control studies.
AB  - The Arg194Trp polymorphism in the X-ray cross-complementing group 1 (XRCC1) had
      been implicated in cancer susceptibility. The previous published data on the
      association between XRCC1 Arg194Trp polymorphism and cancer risk remained
      controversial. Hence, we performed a meta-analysis to investigate the association
      between cancer susceptibility and XRCC1 Arg194Trp (59,227 cases and 81,587
      controls from 201 studies) polymorphism in different inheritance models. We used
      odds ratios with 95 % confidence intervals to assess the strength of the
      association. Overall, significantly increased cancer risk was found (recessive
      model: (odds ration [OR] = 1.18, 95% confidence interval [CI] = 1.09-1.27;
      homozygous model: OR = 1.21, 95% CI = 1.10-1.33; additive model: OR = 1.05, 95%
      CI = 1.01-1.09) when all eligible studies were pooled into the meta-analysis. In
      further stratified and sensitivity analyses, significantly increased glioma risk
      was found among Asians, significantly decreased lung cancer risk was found among
      Caucasians, and significant increased breast cancer risk was found among hospital
      based studies. In summary, this meta-analysis suggests that Arg194Trp
      polymorphism may be associated with increased breast cancer risk, Arg194Trp
      polymorphism is associated with increased glioma risk among Asians, and Arg194Trp
      polymorphism is associated with decreased lung cancer risk among Caucasians. In
      addition, our work also points out the importance of new studies for Arg194Trp
      association in some cancer types, such as gastric, pancreatic, prostate, and
      nasopharyngeal cancers, where at least some of the covariates responsible for
      heterogeneity could be controlled, to obtain a more conclusive understanding
      about the function of the XRCC1 Arg194Trp polymorphism in cancer development (I
      (2) > 75%).

PMID- 25064615
TI  - Determinants of the prevalence of gout in the general population: a systematic
      review and meta-regression.
AB  - Studies on the occurrence of gout show a large range in estimates. However, a
      clear insight into the factors responsible for this variation in estimates is
      lacking. Therefore, our aim was to review the literature on the prevalence and
      incidence of gout systematically and to obtain insight into the degree of and
      factors contributing to the heterogeneity. We searched MEDLINE, EMBASE, and Web
      of Science (January 1962 to July 2012) to identify primary studies on the
      prevalence and incidence of gout in the general population. Data were extracted
      by two persons on sources of clinical heterogeneity, methodological
      heterogeneity, and variation in outcome reporting. Meta-analysis and meta
      regression analysis were performed for the prevalence of gout. Of 1,466 articles
      screened, 77 articles were included, of which 71 reported the prevalence and 12
      the incidence of gout. The pooled prevalence (67 studies; N = 12,226,425) based
      on a random effects model was 0.6% (95% CI 0.4; 0.7), however there was a high
      level of heterogeneity (I(2) = 99.9%). Results from a mixed-effects meta
      regression model indicated that age (p = 0.019), sex (p < 0.001), continent (p <
      0.001), response rate (p = 0.016), consistency in data collection (p = 0.002),
      and case definition (p < 0.001) were significantly associated with gout
      prevalence and jointly accounted for 88.7% of the heterogeneity. The incidence in
      the total population ranged from 0.06 to 2.68 per 1,000 person-years. In
      conclusion, gout is a common disease and the large variation in the prevalence
      data on gout is explained by sex, continent on which the study was performed, and
      the case definition of gout.

PMID- 25064617
TI  - National registers and their use for medical research.

PMID- 25064616
TI  - A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer.
AB  - To inform risk assessment and regulatory decision-making, the relationship
      between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires
      clarification. This article systematically and critically reviews the
      epidemiologic evidence on the association between exposure to TCDD or Agent
      Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate
      cancer risk. Articles evaluated include 11 studies of three cohorts, four case
      control or cross-sectional studies, and three case-only studies of military
      veterans with information on estimated Agent Orange or TCDD exposure; 13 studies
      of seven cohorts, one case-control study, and eight proportionate morbidity or
      mortality studies of Vietnam veterans without information on Agent Orange
      exposure; 11 cohort studies of workers with occupational exposure to TCDD; and
      two studies of one community cohort with environmental exposure to TCDD. The most
      informative studies, including those of Vietnam veterans involved in Agent Orange
      spraying or other handling, herbicide manufacturing or spraying workers with
      occupational TCDD exposure, and community members exposed to TCDD through an
      industrial accident, consistently reported no significant increase in prostate
      cancer incidence or mortality. Only some potentially confounded studies of
      Vietnam veterans compared with the general population, studies with unreliable
      estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam
      veterans reported positive associations. Overall, epidemiologic research offers
      no consistent or convincing evidence of a causal relationship between exposure to
      Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is
      needed in large epidemiologic studies to rule out a causal association more
      conclusively. 

PMID- 25064618
TI  - A pilot study of a genetic CJD risk factor (E200K) in the general Slovak
      population.

PMID- 25064620
TI  - Influence of urban land development and subsequent soil rehabilitation on soil
      aggregates, carbon, and hydraulic conductivity.
AB  - Urban land use change is associated with decreased soil-mediated ecosystem
      services, including stormwater runoff mitigation and carbon (C) sequestration. To
      better understand soil structure formation over time and the effects of land use
      change on surface and subsurface hydrology, we quantified the effects of urban
      land development and subsequent soil rehabilitation on soil aggregate size
      distribution and aggregate-associated C and their links to soil hydraulic
      conductivity. Four treatments [typical practice (A horizon removed, subsoil
      compacted, A horizon partially replaced), enhanced topsoil (same as typical
      practice plus tillage), post-development rehabilitated soils (compost
      incorporation to 60-cm depth in subsoil; A horizon partially replaced plus
      tillage), and pre-development (undisturbed) soils] were applied to 24 plots in
      Virginia, USA. All plots were planted with five tree species. After five years,
      undisturbed surface soils had 26 to 48% higher levels of macroaggregation and 12
      to 62% greater macroaggregate-associated C pools than those disturbed by urban
      land development regardless of whether they were stockpiled and replaced, or
      tilled. Little difference in aggregate size distribution was observed among
      treatments in subsurface soils, although rehabilitated soils had the greatest
      macroaggregate-associated C concentrations and pool sizes. Rehabilitated soils
      had 48 to 171% greater macroaggregate-associated C pool than the other three
      treatments. Surface hydraulic conductivity was not affected by soil treatment
      (ranging from 0.4 to 2.3 cm h(-1)). In deeper regions, post-development
      rehabilitated soils had about twice the saturated hydraulic conductivity (14.8
      and 6.3 cm h(-1) at 10-25 cm and 25-40 cm, respectively) of undisturbed soils and
      approximately 6-11 times that of soils subjected to typical land development
      practices. Despite limited effects on soil aggregation, rehabilitation that
      includes deep compost incorporation and breaking of compacted subsurface layers
      has strong potential as a tool for urban stormwater mitigation and soil
      management should be explicitly considered in urban stormwater policy.

PMID- 25064619
TI  - Association of adiponectin and leptin with relative telomere length in seven
      independent cohorts including 11,448 participants.
AB  - Oxidative stress and inflammation are major contributors to accelerated age
      related relative telomere length (RTL) shortening. Both conditions are strongly
      linked to leptin and adiponectin, the most prominent adipocyte-derived protein
      hormones. As high leptin levels and low levels of adiponectin have been
      implicated in inflammation, one expects adiponectin to be positively associated
      with RTL while leptin should be negatively associated. Within the ENGAGE
      consortium, we investigated the association of RTL with adiponectin and leptin in
      seven independent cohorts with a total of 11,448 participants. We performed
      partial correlation analysis on Z-transformed RTL and LN-transformed
      leptin/adiponectin, adjusting for age and sex. In extended models we adjusted for
      body mass index (BMI) and C-reactive protein (CRP). Adiponectin showed a
      borderline significant association with RTL. This appeared to be determined by a
      single study and when the outlier study was removed, this association
      disappeared. The association between RTL and leptin was highly significant (r = 
      0.05; p = 1.81 * 10(-7)). Additional adjustment for BMI or CRP did not change the
      results. Sex-stratified analysis revealed no difference between men and women.
      Our study suggests that high leptin levels are associated with short RTL. 

PMID- 25064621
TI  - Epigenetically modified nucleotides in chronic heroin and cocaine treated mice.
AB  - Epigenetic changes include the addition of a methyl group to the 5' carbon of the
      cytosine ring, known as DNA methylation, which results in the generation of the
      fifth DNA base, namely 5-methylcytosine. During active or passive demethylation,
      an intermediate modified base is formed, 5-hydroxymethylcytosine. We have
      currently quantified 5-methylcytosine and 5-hydroxymethylcytosine in the liver
      and brain of mice treated with cocaine or heroin, using liquid
      chromatography/tandem mass spectrometry (LC-MS/MS). Our results show that global
      5-methylcytosine levels are not affected by heroin or cocaine administration,
      neither in the liver nor in the brain. However, 5-hydroxymethylcytosine levels
      are reduced in the liver following cocaine administration, while they are not
      affected by cocaine in the brain or by heroin administration in the liver and the
      brain. Elucidation of the epigenetic phenomena that takes place with respect to
      drug abuse and addiction, via quantitative analysis of different modified bases,
      may enable a better understanding of the underlying mechanisms and may lead to
      more personalized and effective treatment options. 

PMID- 25064622
TI  - Gene expression markers in the zebrafish embryo reflect a hepatotoxic response in
      animal models and humans.
AB  - The zebrafish embryo (ZFE) is a promising non-rodent model in toxicology, and
      initial studies suggested its applicability in detecting hepatotoxic responses.
      Here, we hypothesize that the detailed analysis of underlying mechanisms of
      hepatotoxicity in ZFE contributes to the improved identification of hepatotoxic
      properties of new compounds and to the reduction of rodents used for screening.
      ZFEs were exposed to nine reference hepatotoxicants, targeted at induction of
      cholestasis, steatosis and necrosis, and two non-hepatotoxic controls.
      Histopathology revealed various specific morphological changes in the ZFE
      hepatocytes indicative of cell injury. Gene expression profiles of the individual
      compounds were generated using microarrays. Regulation of single genes and of
      pathways could be linked to hepatotoxic responses in general, but phenotype
      specific responses could not be distinguished. Hepatotoxicity-associated pathways
      included xenobiotic metabolism and oxidoreduction related pathways. Overall
      analysis of gene expression identified a limited set of potential biomarkers
      specific for a common hepatotoxicity response. This set included several
      cytochrome P450 genes (cyp2k19, cyp4v7, cyp2aa3), genes related to liver
      development (pklr) and genes important in oxidoreduction processes (zgc:163022,
      zgc:158614, zgc:101858 and sqrdl). In conclusion, the ZFE model allows for
      identification of hepatotoxicants, without discrimination into specific
      phenotypes. 

PMID- 25064623
TI  - Functional reconstruction of subtotal thumb metacarpal defect with a vascularized
      medial femoral condyle flap: case report.
AB  - Devastating hand injuries require customized reconstructive strategies to
      maximize functional outcomes. We report a case of thumb metacarpal reconstruction
      using a vascularized medial femoral condyle osteocutaneous flap in the setting of
      nearly complete metacarpal loss. In addition to achieving the traditional goals
      of reconstructing thumb length and providing stability, the medial femoral
      condyle flap allowed motion at the carpometacarpal joint. The patient's hand
      function was further optimized by a component transfer of a proximally injured
      but distally preserved index finger to the amputated middle finger position. The
      patient regained satisfactory grip and thumb function with minimal donor site
      morbidity. This case highlights the role of both creative and established
      approaches to reconstruct composite tissues following devastating hand injury. 

PMID- 25064624
TI  - Free functioning gracilis transfer for traumatic brachial plexus injuries in
      children.
AB  - PURPOSE: To report our technique and experience with use of free functioning
      muscle transfer (FFMT) in reconstruction of traumatic brachial plexus injuries
      (BPIs) in children as well as its complications and outcomes. METHODS: Twelve
      patients with complete BPI underwent FFMT for reconstruction between 2000 and
      2012. Eight had single-stage gracilis transfer for restoration of elbow flexion,
      and 4 children had double free gracilis muscle transfer for restoration of elbow
      flexion and prehension. Mean duration of follow-up was 27 months (range, 14-55
      mo). RESULTS: Eleven out of 12 patients achieved at least M3 elbow flexion, with
      8 patients achieving M4 or greater elbow flexion. Eight of 12 patients had nerve
      transfers to the musculocutaneous nerve. Mean active elbow arc of motion was 79
      degrees  (range, 30 degrees -130 degrees ). Two patients aged 8 and 11 years with
      open growth plates developed elbow joint contractures, which limited range of
      motion, but they recovered M4 and M5 elbow flexion strength. CONCLUSIONS: FFMTs
      can result in good outcomes following reconstruction for traumatic BPI. The use
      of FFMT should be carefully considered in children prior to skeletal maturity
      because of the risk of the development of an elbow flexion contracture. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25064625
TI  - Effects of empiric antifungal therapy for septic shock on time to appropriate
      therapy for Candida infection: a pilot study.
AB  - PURPOSE: Inappropriate initial therapy for Candida-related septic shock is common
      and associated with a high mortality rate. This before-after pilot study was
      conducted to determine the feasibility of using empiric therapy for reducing the
      time to appropriate antifungal therapy in patients with Candida-related septic
      shock. METHODS: Patients aged 18-99 years with septic shock presenting to Barnes
      Jewish Hospital, St. Louis, Missouri, in 2012-2013 were assigned to 1 of 2
      groups. Patients presenting between January 1, 2012, and December 31, 2012, were
      managed according to local standard of care for patients with septic shock, to
      include antifungal therapy at the discretion of the treating physician (standard
      therapy group). Patients presenting between January 1, 2013, and December 31,
      2013, received empiric antifungal therapy (primarily micafungin 100 mg/d or
      fluconazole 800 mg on day 1, followed by 400 mg/d), facilitated by a clinical
      pharmacist in the medical intensive care unit, until microbiologic cultures were
      available to determine the cause of septic shock (empiric therapy group). The
      primary outcome was time to appropriate therapy after shock onset. FINDINGS: A
      total of 28 patients were enrolled (mean age, 56.3 [15.1] years [range, 30-92
      years]; 16 [57.1%] men). The time to appropriate therapy after shock onset was
      statistically shorter with empiric therapy (n = 13) compared with standard
      therapy (n = 15) (10.6 [15.8] vs 40.5 [26.0] hours; P = 0.001). Patients
      receiving empiric therapy were more likely to have received appropriate therapy
      within 12 hours (69.2% vs 6.7%; P = 0.001) and within 24 hours (76.9% vs 40.0%; P
      = NS) of shock onset. In an analysis to determine the number of septic shock
      patients needed to be treated with empiric antifungal therapy for 1 patient with
      Candida-related septic shock to receive appropriate treatment, 256 patients
      without Candida infection received a total of 687 doses of empiric antifungal
      therapy (mean, 2.7 doses per patient) compared with 136 patients who received 382
      doses of standard antifungal therapy (mean, 2.8 doses per patient); the number
      needed to treat was 19.6. IMPLICATIONS: The present pilot study demonstrated that
      the use of empiric antifungal therapy for Candida-related septic shock was
      associated with a statistically shorter time to administration of appropriate
      treatment. ClinicalTrials.gov identifier.

PMID- 25064627
TI  - Comparison of treatment modalities in syndromic children with obstructive sleep
      apnea--a randomized cohort study.
AB  - INTRODUCTION: Obstructive Sleep Apnea (OSA) is a common medical problem in adults
      that is becoming increasingly recognized in children. It occurs in the pediatric
      age group, from newborns to teens. More recently, many specialists have estimated
      OSA prevalence to be between 5 and 6%. However, in syndromic children, the
      prevalence of OSA can be from 50 to 100%, having a significant effect on their
      Quality-of-Life. As they are a challenging population for management, it is
      essential to evaluate them thoroughly before planning appropriate intervention.
      OBJECTIVE: To compare the efficacy of Adenotonsillectomy (T&A) and Continuous
      Positive Airway Pressure (CPAP) in syndromic children [Down syndrome (DS) and
      Mucopolysaccharidoses (MPS)] with Obstructive Sleep Apnea (OSA). MATERIALS AND
      METHODS: In a prospective, randomized, cohort comparative study, 124 syndromic
      children (DS and MPS) aged between 6 and 12 years were recruited from a private
      MPS support group and the Down Syndrome Society, Chennai. A standard assessment
      was performed on all children who entered the study including a full overnight
      Polysomnogram (PSG), Epworth Sleepiness Scale-Children (ESS-C) and Quality-of
      Life (QOL) tool OSA-18. The children with positive PSG who consented for the
      study (n = 80) were randomly distributed to two groups, T&A group & CPAP group.
      The children were followed up with repeat PSG, clinical evaluation, ESS-C and
      Quality-of-Life (QOL) tool OSA-18 for a period of 1 year. OBSERVATION AND
      RESULTS: Follow-up was available for 73 syndromic children. Both the groups, T&A
      group and CPAP group, showed statistically significant (p < 0.05) improvement in
      Apnea-Hypoapnea Index (AHI), ESS-C, QOL from the intervention. In our study, T&A
      showed equal outcome compared to CPAP. The contrasting feature between the two
      groups was that CPAP use gave immediate sustained improvement while T&A gave
      gradual progressive improvement of symptoms over a period of 1 year. CONCLUSION:
      On average, T&A gives equal outcomes as CPAP and it can be suggested as a first
      line treatment in this group of syndromic children.

PMID- 25064628
TI  - Surgical outcomes with subperiosteal pocket technique for cochlear implantation
      in very young children.
AB  - OBJECTIVES: As data continue to emerge demonstrating improved hearing outcomes
      associated with younger age at time of cochlear implantation, more children aged
      12 months or younger are undergoing this procedure. Drilling a well to house the
      cochlear implant receiver/stimulator (R/S) may carry an increased risk in this
      group of patients as the calvarium is thin and drilling an adequate well may
      require exposure of the underlying dura. Our group has employed a technique in
      this age group which involves securing the R/S in a subperiosteal pocket without
      creating a bony well. We report our experience with six infants 12 months of age
      or younger undergoing cochlear implantation with the subperiosteal pocket
      technique. METHODS: Cases were identified by searching an IRB approved research
      registry. Charts were reviewed for demographics, surgical technique, and clinical
      outcomes. Descriptive statistics were calculated. RESULTS: Six patients 12 months
      of age or younger underwent cochlear implantation over a one year period.
      Simultaneous bilateral implantation was performed in all cases, for a total of 12
      implanted ears. The average age at time of implantation was 9.8 months (SD 2.1
      months). There were no postoperative wound complications. No evidence of device
      migration was noted in any patient as of the most recent follow-up appointment.
      There was one device hard failure at 32 months. Average length of follow-up was
      28.4 months (SD 13.8 months). CONCLUSIONS: No wound complications or device
      migrations occurred in 12 cochlear implantations in six children aged 12 months
      or younger. Advantages of this technique include no risk to the dura in this
      location, smaller incisions, and shorter surgical time. A potential disadvantage
      is the increased device profile from the lack of a well. New thinner implant
      designs may minimize this concern. Further prospective study is justified to
      confirm our initial experience in this small group.

PMID- 25064626
TI  - Effect of low birth weight on women's health.
AB  - PURPOSE: The theory of the developmental origins of health and disease
      hypothesizes that low birth weight (<=5.5 lb) indicative of poor fetal growth is
      associated with an increased risk of chronic, noncommunicable disease in later
      life, including hypertension, type 2 diabetes mellitus, and osteoporosis. Whether
      women are at greater risk than men is not clear. Experimental studies that mimic
      the cause of slow fetal growth are being used to examine the underlying
      mechanisms that link a poor fetal environment with later chronic disease and
      investigate how sex and age affect programmed risk. Thus, the aims of this review
      are to summarize the current literature related to the effect of low birth weight
      on women's health and provide insight into potential mechanisms that program
      increased risk of chronic disease across the lifespan. METHODS: A search of
      PubMed was performed with the keywords low birth weight, women's health, female,
      and sex differences; additional terms included blood pressure, hypertension,
      renal, cardiovascular, obesity, glucose intolerance, type 2 diabetes,
      osteoporosis, bone health, reproductive senescence, menopause, and aging.
      FINDINGS: The major chronic diseases associated with low birth weight include
      high blood pressure and cardiovascular disease, impaired glucose homeostasis and
      type 2 diabetes, impaired bone mass and osteoporosis, and early reproductive
      aging. IMPLICATIONS: Low birth weight increases the risk of chronic disease in
      men and women. Low birth weight is also associated with increased risk of early
      menopause. Further studies are needed to fully address the effect of sex and age
      on the developmental programming of adult health and disease in women across
      their lifespan.

PMID- 25064629
TI  - Efficacy of long-term 4.0 g/day mesalazine (Pentasa) for maintenance therapy in
      ulcerative colitis.
AB  - BACKGROUND: High-dose (4.0 g/day) mesalazine is typically used for induction
      therapy, but its efficacy as maintenance therapy remains to be determined. We
      conducted a multicenter retrospective study to investigate the efficacy of
      continuous treatment with 4.0 g/day of mesalazine. MATERIAL/METHODS: Japanese
      ulcerative colitis (UC) patients receiving acute induction therapy with 4.0 g/day
      mesalazine were enrolled and followed. Those who clinically improved or who
      achieved clinical remission were categorized into 2 sub-groups according to the
      median duration of treatment with 4.0 g/day of mesalazine. The clinical relapse
      frequency and the time to relapse were analyzed. RESULTS: We enrolled 180
      patients with active UC, and then 115 patients who clinically improved or who
      achieved clinical remission after treatment with 4.0 g/day mesalazine were
      categorized into 2 sub-groups according to the median of treatment duration: a
      short-term treatment group (<=105 days, n=58) and a long-term treatment group
      (>105 days, n=57). Overall, 45 (39.1%) patients relapsed: 28 (48.3%) in the short
      term treatment group and 17 (29.8%) in the long-term treatment group. This
      difference was statistically significant (p<0.05). The relapse-free rate in the
      long-term treatment group was significantly higher than that in the short-term
      treatment group (p<0.05). The mean time to relapse in the long-term treatment
      group was significantly longer than that in the short-term treatment group
      (425.6+/-243.8 days vs. 277.4+/-224.5 days; p<0.05). CONCLUSIONS: Long-term
      continuous treatment with high-dose mesalazine (4.0 g/day) may be more effective
      than short-term treatment for maintenance of remission in UC patients.

PMID- 25064630
TI  - Association analysis of melanocortin 3 receptor polymorphisms with the risk of
      pulmonary tuberculosis.
AB  - PURPOSE: Melanocortin 3 Receptor (MC3R) is one of the families of seven
      transmembrane G-protein-coupled receptors, and a recent study showed that MCR3
      promoter polymorphism was significantly associated with the susceptibility of
      tuberculosis (TB) in South African population. METHODS: We analyzed six MC3R
      polymorphisms to examine the genetic effects on the risk of pulmonary TB in
      Korean subjects by using TaqMan assays and case-control analyses. RESULTS: Using
      statistical analyses, one common promoter polymorphism (MC3R rs11575886 T > C)
      was found to be associated with an increased risk of pulmonary TB. The frequency
      of the C-bearing genotype of rs11575886 was higher in pulmonary TB patients than
      in normal controls (p = 0.03, OR = 1.46) although the significance was not
      retained after correction. In silico analysis for the difference of transcription
      binding factor (TF), motif between C and T allele demonstrated that the TF motif
      and its threshold scores of C allele were lower than those of T allele.
      CONCLUSIONS: The C allele of rs11575886 could be a risk allele for the pulmonary
      TB by affecting the binding of TF. Our findings suggest that polymorphisms in
      MC3R might be one of genetic factors for the risk of pulmonary TB development in
      Korean subjects.

PMID- 25064631
TI  - Prediction of pulmonary restriction from forced vital capacity in elderly is
      similar using GLI and ERS equations.
AB  - INTRODUCTION: The prevalence of pulmonary restriction increases in the elderly
      and detection could be challenging due to the difficulty in measuring lung
      volumes in older patients. The recently published Global Lung Function Initiative
      (GLI) equations were found to predict better restriction in middle-aged patients
      compared to ERS'93 norms. However, the ability of the GLI equations to detect
      pulmonary restriction in older patients has not been investigated. PATIENTS AND
      METHODS: We extracted spirometric data in patients older than 85 years from the
      database of our pulmonary function testing laboratory. The population with
      pulmonary restriction was defined as those having a total lung capacity value
      (TLC) below the lower limit of normal (LLN) using ERS'93 equations. We then
      compared the ability of the ERS'93 and GLI equations to detect this when the
      forced vital capacity (FVC) was below the LLN. RESULTS: We analyzed data from 285
      patients. A true restrictive defect was found in 66 patients (23%). Sensitivity
      to detect a reduced TLC was higher when calculated from the GLI than the ERS'93
      equations, (70 vs 45%). By contrast, specificity was lower (74 vs 89%,
      respectively); there was no difference in the negative predictive value (89 and
      84%). Using receiver operating curves, both sets of equations performed similarly
      to detect spirometric restriction. CONCLUSIONS: In conclusion, both sets of
      equations similarly predicted a pulmonary restriction in older subjects. The high
      negative predictive value of the GLI equations thus allows for static lung volume
      measurement to be avoided in older patients when the FCV exceeds the LLN whatever
      the predicted equation used.

PMID- 25064632
TI  - Predictors of hospital stay and mortality in dengue virus infection-experience
      from Aga Khan University Hospital Pakistan.
AB  - BACKGROUND: Dengue virus infection (DVI) is very common infection. There is
      scarcity of data on factor associated with increased hospital stay and mortality
      in dengue virus infection (DVI). This study was done to know about factors
      associated with increased hospital stay and mortality in patients admitted with
      DVI. RESULTS: Out of 532 patients, two third (72.6%) had stay <=3 days while one
      third (27.4%) had stay greater than 3 days. The mean length of hospital stay was
      3.46 +/- 3.45 days. Factors associated with increased hospital stay (>3 days)
      included AKI (acute kidney injury) (Odd ratio 2.98; 95% CI 1.66-5.34), prolonged
      prothrombin time (Odd ratio 2.03; 95% CI 1.07-3.84), prolonged activated partial
      thromboplastin time (aPTT) (Odd ratio 1.80; CI 95% 1.15-2.83) and increased age
      of > 41.10 years (Odd ratio 1.03; CI 95% 1.01-1.04).Mortality was 1.5%. High
      mortality was found in those with AKI (P <0.01), dengue hemorrhagic fever (DHF)
      and dengue shock syndrome (DSS) (P <0.001), respiratory failure (P0.01), prolong
      PT (P 0.001), prolong aPTT (P0.01) and increased hospital stay (P0.04).
      CONCLUSION: Increasing age, coagulopathy and acute kidney injury in patients with
      DVI is associated with increased hospital stay. Morality was more in patients
      with AKI, DHF and DSS, respiratory failure, coagulopathy and these patients had
      more prolonged hospitalization.

PMID- 25064633
TI  - Curcumin inhibits monocyte chemoattractant protein-1 expression and enhances
      cholesterol efflux by suppressing the c-Jun N-terminal kinase pathway in
      macrophage.
AB  - OBJECTIVE: To investigate the effect of curcumin on monocyte chemoattractant
      protein 1 (MCP-1) production and reverse cholesterol transport (RCT) in
      macrophage induced by oxidation low-density lipoprotein (ox-LDL), and to identify
      the signal pathways involved. METHODS: The macrophages were treated with ox-LDL
      and various concentrations of curcumin simultaneously. The MCP-1 expression was
      measured by enzyme-linked immunosorbent assay. The apoAI-mediated cholesterol
      efflux was measured by (3)H-cholesterol-labeled counting radioactivity. The
      activation of intracellular signaling pathways was studied by Western blotting.
      RESULTS: Curcumin decreased the production of MCP-1 induced by ox-LDL in
      macrophages. MCP-1 expression was restrained by the inhibition of c-Jun N
      terminal kinase (JNK) pathway (SP600125) and NF-kappaB pathway (BAY11-7082).
      Curcumin suppressed the phosphorylation of JNK and activation of NF-kappaB.
      Curcumin also enhanced RCT via up-regulating the expression of liver X receptor
      alpha (LXRalpha), ATP-binding cassette transporter A1 (ABCA1) and scavenger
      receptor class B type I (SR-BI). Additionally, the inhibition of JNK (SP600125)
      increased cholesterol efflux and increased the expression of ABCA1 and SR-BI, but
      had no effect on LXRalpha. CONCLUSION: Curcumin suppresses MCP-1 production
      induced by ox-LDL via the JNK pathway and NK-kappaB pathway, while enhances
      cholesterol efflux in macrophage via suppressing the JNK pathway and activating
      the LXR-ABCA1/SR-BI pathway, which indicate that the vascular protective effect
      of curcumin is related to anti-inflammation and anti-atherosclerosis.

PMID- 25064634
TI  - Reactive oxygen and nitrogen (ROS and RNS) species generation and cell death in
      tomato suspension cultures--Botrytis cinerea interaction.
AB  - This article reports events connected to cell survival and Botrytis cinerea
      infection development in cell suspension cultures of two tomato cultivars which
      show different levels of susceptibility to the pathogen: cv. Corindo (more
      susceptible) and cv. Perkoz (less susceptible). In parallel changes in reactive
      oxygen (ROS) and nitrogen (RNS) species generation and in S-nitrosoglutathione
      reductase (GSNOR) activity were studied. In vivo staining methods with acridine
      orange (AO) and ethidium bromide (EB) as well as fluorescent microscopy were used
      to assess tomato and B. cinerea cells death. The biochemical studies of ROS and
      RNS concentrations in plant cell extract were complemented by in vivo ROS and
      nitric oxide (NO) imaging using nitro blue tetrazolium (NBT), diaminobenzidine
      (DAB) and diaminofluorescein diacetate (DAF-DA) staining methods, and confocal
      microscope technique. B. cinerea infection proceeded slower in Perkoz cell
      cultures. It was evidenced by measuring the pathogen conidia germination and
      germination tube development in which nuclei revealing cell death dominated. Two
      different types of tomato cell death were observed: cells with necrotic nuclei
      dominated in Corindo whereas in Perkoz cells with characteristic of vacuolar
      death type prevailed. In Perkoz cells, constitutive levels of NO and S
      nitrosothiols (SNO) were significantly higher and hydrogen peroxide (H2O2) and
      superoxide anion (O2(-)) concentrations were slightly higher as compared with
      Corindo cells. Moreover, increases in these molecule concentrations as a result
      of B. cinerea inoculation were observed in both, Perkoz and Corindo cell
      cultures. The enzymatic GSNOR activity seems to be an important player in
      controlling the SNO level in tomato cells. Involvements of the studied compounds
      in molecular mechanisms of tomato resistance to B. cinerea are discussed in the
      paper.

PMID- 25064635
TI  - Nonlinear frequency mixing in a resonant cavity: numerical simulations in a
      bubbly liquid.
AB  - The study of nonlinear frequency mixing for acoustic standing waves in a
      resonator cavity is presented. Two high frequencies are mixed in a highly
      nonlinear bubbly liquid filled cavity that is resonant at the difference
      frequency. The analysis is carried out through numerical experiments, and both
      linear and nonlinear regimes are compared. The results show highly efficient
      generation of the difference frequency at high excitation amplitude. The large
      acoustic nonlinearity of the bubbly liquid that is responsible for the strong
      difference-frequency resonance also induces significant enhancement of the
      parametric frequency mixing effect to generate second harmonic of the difference
      frequency. 

PMID- 25064636
TI  - Factors associated with the outcomes of endoscopic submucosal dissection in
      pyloric neoplasms.
AB  - BACKGROUND: Pyloric neoplasms are one of the most technically difficult lesions
      to remove by endoscopic submucosal dissection (ESD). OBJECTIVE: To evaluate the
      therapeutic outcomes of ESD in pyloric neoplasms according to clinicopathologic
      characteristics and to assess predictive factors for incomplete resection.
      DESIGN: A retrospective, single-center study. PATIENTS: A total of 110 cases of
      pyloric adenomas and early cancers treated with ESD from January 2007 to May 2013
      were included. INTERVENTION: ESD procedures with or without retroflexion maneuver
      were used in all qualifying cases. MAIN OUTCOME MEASUREMENTS: Therapeutic
      outcomes of ESD and procedure-related adverse events. RESULTS: Complete resection
      rates differed significantly in relation to location (pylorus vs pylorus with
      duodenal extension, 79% vs 58%), directional distribution (upper hemisphere vs
      lower hemisphere of the pylorus, 67% vs 90%), tumor size (<= 10 mm vs > 10 mm,
      84% vs 67%), and circumferential extent of pyloric mucosal resection (<= 1/2 vs >
      1/2, 92% vs 62%). On multivariate analysis, tumor location (pylorus with duodenal
      extension; odds ratio 5.747), hemispheric distribution (upper hemisphere; odds
      ratio 4.906), and circumferential extent of resection (> 1/2; odds ratio 3.960)
      were independent factors associated with incomplete resection. The rates of
      procedure-related bleeding, stenosis, and perforation were 8%, 1%, and 1%,
      respectively; none of the adverse events required surgical intervention.
      LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: ESD is a safe,
      effective, and feasible treatment for pyloric neoplasms. However, the complete
      resection rate decreases for tumors that have duodenal extension, are located in
      the upper hemisphere, and have large circumferential extent of resection.

PMID- 25064637
TI  - A novel technique for over-the-scope clip application: a safer and more secure
      method.

PMID- 25064639
TI  - Expanding the C. elegans toolbox into a toolshed.

PMID- 25064638
TI  - Increased prevalence of lung, breast, and pancreatic cancers in addition to
      melanoma risk in families bearing the cyclin-dependent kinase inhibitor 2A
      mutation: implications for genetic counseling.
AB  - BACKGROUND: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is the major high-risk
      susceptibility gene for melanoma. OBJECTIVE: We sought to evaluate the effect of
      CDKN2A mutations in Spanish patients with a high risk of developing melanoma and
      the association with clinical and family history features. METHODS: A cross
      sectional study design was used to analyze the CDKN2A impact in 702 Spanish
      patients with a high risk of developing melanoma. RESULTS: The CDKN2A mutation
      prevalence was 8.5% in patients with sporadic multiple primary melanoma and 14.1%
      in familial melanoma. Number of cases in the family, number of primary melanomas,
      and age of onset were associated with the presence of CDKN2A mutation. Having a
      CDKN2A mutation in the family increased the prevalence of other cancers
      (prevalence ratio [PR] 2.99, P=.012) and prevalence of pancreatic (PR 2.97,
      P=.006), lung (PR 3.04, P<.001), and breast (PR 2.19, P=.018) cancers but not
      nephrourologic or colon cancer. LIMITATIONS: Smoking status was not assessed in
      the individuals with lung cancer. CONCLUSIONS: Melanoma-prone families with
      mutations in CDKN2A have an increased prevalence of a broad spectrum of cancers
      including lung, pancreatic, and breast cancer. This information should be
      included in genetic counseling and cancer prevention programs for CDKN2A mutation
      carriers.

PMID- 25064640
TI  - An investigation of the performance of novel chorded keyboards in combination
      with pointing input devices.
AB  - Rapid advances in computing power have driven the development of smaller and
      lighter technology products, with novel input devices constantly being produced
      in response to new user behaviors and usage contexts. The aim of this research
      was to investigate the feasibility of operating chorded keyboard control modules
      in concert with pointing devices such as styluses and mice. We compared
      combinations of two novel chorded keyboards with different pointing devices in
      hopes of finding a better combination for future electronic products. Twelve
      participants were recruited for simulation testing, and paired sample t testing
      was conducted to determine whether input and error rates for the novel keyboards
      were improved significantly over those of traditional input methods. The most
      efficient input device combination tested was the combination of a novel cross
      shaped key keyboard and a stylus, suggesting the high potential for use of this
      combination with future mobile IT products. 

PMID- 25064641
TI  - Cohort Profile: The Manitoba Follow-up Study (MFUS).
AB  - The Manitoba Follow-up Study (MFUS) is Canada's longest running study of
      cardiovascular disease and ageing. The MFUS cohort consists of 3983 men recruited
      from the Royal Canadian Air Force at the end of World War II. At entry to the
      study, 1 July 1948, their mean age was 31 years, with 90% between ages 20 and 39
      years. All study members were free of clinical evidence of ischaemic heart
      disease. The protocol of MFUS was to obtain routine medical examinations from
      these men at regular intervals over time. The research goal of the study was to
      examine the role that any abnormalities detected on routine electrocardiograms
      from apparently healthy men might play in the prediction of subsequent diagnoses
      of cardiovascular disease. Over the course of 65 years, about 35% of the cohort
      has documented evidence of ischaemic heart disease. The research focus was
      expanded in 1996 to explore the roles of physical, mental and social functioning
      in support of healthy and successful ageing. On 1 July 2013, 429 original cohort
      members were alive with a mean age of 92 years. Collaborative research with
      others outside the in-house team is welcomed. 

PMID- 25064642
TI  - Economically inactive, unemployed and employed suicides in Australia by age and
      sex over a 10-year period: what was the impact of the 2007 economic recession?
AB  - BACKGROUND: Suicide is higher among economically inactive and unemployed persons
      than employed persons. This paper investigates differences in this relationship
      by sex and age over the period 2001 to 2010 in Australia. It also examines
      changes in suicide among employed, unemployed and economically inactive persons
      during the recession of 2007-09. METHOD: Suicide data from the National Coroners
      Information System were utilised for this retrospective study. Negative binomial
      and Poisson regression was used to estimate the association between suicide and
      employment status and to investigate differences in suicide rates over the period
      of the recession (2007-09) compared with the year before the recession (2006).
      RESULTS: Results suggest that during 2001-10 economically inactive/unemployed
      males had a suicide rate ratio (RR) of 4.62 [95% confidence interval (CI) 4.10,
      5.19; P<0.001] compared with employed males (RR=1.00), whereas economically
      inactive/unemployed females had a suicide RR of 8.44 compared with employed
      females (95% CI 7.38, 9.67; P<0.001). There was an increase in suicide among both
      employed (7% rise in 2007, P=0.003) and economically inactive/unemployed males
      during the GFC (22% in 2008, P<0.001). Suicide also increased among economically
      inactive/unemployed females (12% in 2007, P=0.03; 19% in 2008, P=0.001) but not
      among employed females. CONCLUSIONS: These results suggest the need for adequate
      policy and social welfare responses to ameliorate the effects of the economic
      recession on the working age population. Particularly, these should target
      unemployed and economically inactive men and women in Australia, who may be at
      higher risk of suicide than previously thought.

PMID- 25064643
TI  - Development of a metabolomic approach based on urine samples and direct infusion
      mass spectrometry.
AB  - The analysis of urine by direct infusion mass spectrometry suffers from ion
      suppression due to its high salt content and inter-sample variability caused by
      the differences in urine volume between persons. Thus, urine metabolomics
      requires a careful selection of the sample preparation procedure and a
      normalization strategy to deal with these problems. Several approaches were
      tested for metabolomic analysis of urine samples by direct infusion electrospray
      mass spectrometry (DI-ESI-MS), including solid phase extraction, liquid-liquid
      extraction, and sample dilution. In addition, normalization of results based on
      conductivity values and statistical treatment was performed to minimize sample
      variability. Both urine dilution and solid phase extraction with mixed mode
      sorbent considerably reduced the salt content in urine, providing comprehensive
      metabolomic fingerprints. Moreover, statistical data normalization enabled the
      correction of inter-sample physiological variability, improving the quality of
      results obtained. Therefore, high-throughput DI-ESI-MS fingerprinting of urine
      samples can be achieved with simple pretreatment procedures allowing the use of
      this noninvasive sampling in metabolomics. Finally, the optimized approach was
      tested in a pilot metabolomic investigation of urine samples from transgenic mice
      models of Alzheimer's disease (APP/PS1) in order to illustrate the potential of
      the methodology. 

PMID- 25064644
TI  - Effect of the mass of immunoglobulin (Ig)G intake and age at first colostrum
      feeding on serum IgG concentration in Holstein calves.
AB  - Forty-four Holstein calves (19 male and 25 female) were used in this study of the
      relationships among age at first colostrum feeding, IgG intake, and apparent
      efficiency of IgG absorption. Time of birth was recorded for each calf and the
      calves were fed colostrum ad libitum after birth at either 0930 or 1630 h. Blood
      samples were collected immediately before and 24h after colostrum feeding. Data
      from calves were then categorized into 4 groups representing time from birth to
      colostrum feeding: A=fed within 1h (n=5); B=fed from 1 to 6h (n=10); C=fed from 6
      to 12 h (n=21); and D=fed from 12 to 18 h (n=8) after birth. Average total intake
      of colostrum was 3.6 +/- 0.1L. Over 80% of the calves consumed >=3 L of
      colostrum. Apparent efficiency of IgG absorption declined remarkably 12 h after
      birth. Mean apparent efficiency of absorption of IgG in group D (15.8 +/- 3.0%)
      was lower than that in groups A (30.5 +/- 3.9%) and B (27.4 +/- 2.8%). Serum IgG
      concentration in calves was positively correlated with IgG intake in all groups.
      The relationship between mass of IgG consumed and calf serum IgG at 24 h was
      different for each time of colostrum feeding, with only limited differences
      observed between groups A and B. We concluded that failure of transfer of passive
      immunity in newborn calves may be avoided if calves consume >=3 L of colostrum
      with IgG concentration >40 mg/mL within 6 h after birth. These findings help
      define the opportunity to minimize failure of transfer of passive immunity to
      newborn calves under management programs similar to those used on commercial
      dairy farms.

PMID- 25064645
TI  - Short communication: a food-systems approach to assessing dairy product waste.
AB  - Concern about world population increase, food security, and the environmental
      burdens of food production have made food-waste reduction a social and
      environmental priority. In this context, the quantification of dairy product
      waste is especially difficult due to the varied means of disposal, by solid and
      liquid waste streams, and due to inclusion as an ingredient in many processed
      foods. In this study, food intake data from the Australian National Nutrition
      Survey (>13,000 participants; >4,500 food items) were disaggregated into basic
      foods and total national dairy product intake was expressed in whole-milk
      equivalents. This result was compared with total domestic milk supply, indicating
      a level of waste of 29% for dairy products in the Australian food system. With
      national food-waste reduction targets becoming increasingly common, reliable
      estimates of food waste at the national scale are important for goal setting,
      baseline reporting, and performance monitoring. For this purpose, the systems
      approach to assessing food waste demonstrated in this project is deemed to have
      advantages over other common methods of food-waste assessment, such as bin
      audits, waste diaries, and surveys. 

PMID- 25064646
TI  - Short communication: Sensory profile of raw goat milk cheeses made with artisan
      kid rennet pastes from commercial-weight animals: alternative to farmhouse goat
      cheeses.
AB  - The loss of traditional kid rennet pastes in the Canary Islands (Spain), as in
      many other regions, is most likely due to the custom of using abomasa from very
      young animals killed below desirable commercial weight. In addition, the
      reasonable price of commercial rennets (CR) has resulted in the loss of typical
      sensory characteristics for most farmhouse raw goat milk cheeses, placing them at
      a disadvantage when local and international markets are full of different
      cheeses, often with aggressive marketing strategies. This paper analyzes the
      sensory characteristics of raw goat milk cheeses made with rennet pastes prepared
      from commercial kid abomasa in 2 ways: dried while full of ingested milk [full,
      commercial, artisan kid rennet (FCKR)], or dried after being emptied of ingested
      milk and refilled with raw goat milk [empty, commercial, artisan kid rennet
      (ECKR)]. This latter practice allows the use of empty abomasa, or abomasa with
      grass, soil, and so on. Sensory profiles of cheeses made with FCKR and ECKR
      rennets were compared with those made with CR by an expert panel (n=7). The FCKR
      and ECKR cheeses had similar sensory profiles. Although scores for FCKR cheeses
      were somewhat higher than for ECKR cheeses, they were in the range found for
      traditional cheeses made with rennet prepared with abomasa from very young
      animals. The sensory profile of CR cheeses was very different. Almost 90% of
      consumer panelists (n=90) preferred cheeses made with the experimental rennet
      pastes. These results demonstrate the possibility to prepare artisan rennet
      pastes from commercial-weight kids in an easy way for farmhouse cheese makers
      using local resources that would otherwise be destroyed in abattoirs. 

PMID- 25064647
TI  - Effects of different physical forms of wheat grain in corn-based starter on
      performance of young Holstein dairy calves.
AB  - The objective of the present study was to examine the effects of partially
      replacing corn with 2 forms of wheat grain on daily intake of starter feed,
      average daily gain, feed efficiency, rumen pH, fecal score, weaning weight,
      skeletal growth, and blood metabolites of dairy calves. Thirty-two male and
      female Holstein dairy calves (n=8 calves per treatment) were used in a completely
      randomized block design. At d 3 of age, individually housed calves were randomly
      allocated to different treatments consisting of a starter diet with 60% ground
      corn (control), a starter diet with 60% whole corn, a starter diet with 30%
      ground corn plus 30% ground wheat (GCGW), and a starter with 30% ground corn plus
      30% whole wheat (GCWW), with all other components in a meal form. All calves had
      free access to water and feed throughout the study period and received 4 L of
      milk replacer/d from d 3 to 50 and 2 L/d from d 50 to 52; weaning occurred at the
      end of d 52. Feed intake was recorded daily and body weight and skeletal growth
      measures were recorded on d 10 and every 10 d thereafter. Rumen pH was measured
      on d 30, 45, and 60. Blood sample were collected on d 30 and every 10 d
      thereafter through d 70. Data were analyzed using MIXED procedures of SAS (SAS
      Institute Inc., Cary, NC). Over the experimental period (d 1-70), the starter
      intake for the GCWW group was significantly different from the control group, but
      not different from the other groups. Calves fed whole wheat had a significantly
      greater average daily gain compared with other groups over the experimental
      period (d 1-70). Feed efficiency was only better in calves fed the GCWW diet than
      the GCGW group for postweaning and overall periods. No differences were observed
      for preweaning in body length, hip height, or withers height among the
      treatments; however, differences were significant in heart girth and body barrel.
      Postweaning, some of the body measurements were greater in calves fed the GCWW
      and GCGW starter diets. Blood glucose concentration reduced with age; however,
      blood urea nitrogen, beta-hydroxybutyrate, albumin, and total protein increased
      with age. Treatment * time effects on blood urea nitrogen and total protein
      concentrations were detected. Blood urea nitrogen concentration (mg/dL) was
      affected by dietary treatments on d 30, 40, and 70, but no significant difference
      was detected on d 50 and 60. Serum total protein concentration (g/dL) was also
      affected by dietary treatments on d 40 and 70, but no significant difference was
      detected on d 40, 50, and 60. Whereas rumen pH was significantly reduced for the
      control compared with the GCWW treatment on d 45, comparison of the fecal scores
      showed no detectable differences among the treatments. Overall, the results of
      the current study indicate that starter diets containing whole wheat and ground
      corn can improve performance in young dairy calves compared with diets containing
      ground corn/ground wheat, whole corn, or ground corn, under our experimental
      conditions.

PMID- 25064648
TI  - Methane production, nutrient digestion, ruminal fermentation, N balance, and milk
      production of cows fed timothy silage- or alfalfa silage-based diets.
AB  - The objective of this study was to investigate the effects of changing forage
      source in dairy cow diets from timothy silage (TS) to alfalfa silage (AS) on
      enteric CH4 emissions, ruminal fermentation characteristics, digestion, milk
      production, and N balance. Nine ruminally cannulated lactating cows were used in
      a replicated 3 * 3 Latin square design (32-d period) and fed (ad libitum) a total
      mixed ration (TMR; forage:concentrate ratio of 60:40, dry matter basis), with the
      forage portion consisting of either TS (0% AS; 0% AS and 54.4% TS in the TMR), a
      50:50 mixture of both silages (50% AS; 27.2% AS and 27.2% TS in the TMR), or AS
      (100% AS; 54.4% AS and 0% TS in the TMR). Compared with TS, AS contained less
      (36.9 vs. 52.1%) neutral detergent fiber but more (20.5 vs. 13.6%) crude protein
      (CP). In sacco 24-h ruminal degradability of organic matter (OM) was higher for
      AS than for TS (73.5 vs. 66.9%). Replacement of TS with AS in the diet entailed
      increasing proportions of corn grain and bypass protein supplement at the expense
      of soybean meal. As the dietary proportion of AS increased, CP and starch
      concentrations increased, whereas fiber content declined in the TMR. Dry matter
      intake increased linearly with increasing AS proportions in the diet. Apparent
      total-tract digestibility of OM and gross energy remained unaffected, whereas CP
      digestibility increased linearly and that of fiber decreased linearly with
      increasing inclusion of AS in the diet. The acetate-to-propionate ratio was not
      affected, whereas ruminal concentration of ammonia (NH3) and molar proportion of
      branched-chain VFA increased as the proportion of AS in the diet increased. Daily
      CH4 emissions tended to increase (476, 483, and 491 g/d for cows fed 0% AS, 50%
      AS, and 100% AS, respectively) linearly as cows were fed increasing proportions
      of AS. Methane production adjusted for dry matter intake (average=19.8 g/kg) or
      gross energy intake (average=5.83%) was not affected by increasing AS inclusion
      in the diet. When expressed on a fat-corrected milk or energy-corrected milk
      yield basis, CH4 production increased linearly with increasing AS dietary
      proportion. Urinary N excretion (g/d) increased linearly when cows were fed
      increasing amounts of AS in the diet, suggesting a potential for higher nitrous
      oxide (N2O) and NH3 emissions. Efficiency of dietary N use for milk protein
      secretion (g of milk N/g of N intake) declined with the inclusion of AS in the
      diet. Despite marked differences in chemical composition and ruminal
      degradability, under the conditions of this study, replacing TS with AS in dairy
      cow diets was not effective in reducing CH4 energy losses.

PMID- 25064649
TI  - Effects of abomasal infusion of conjugated linoleic acids, Sterculia foetida oil,
      and fish oil on production performance and the extent of fatty acid Delta9
      desaturation in dairy cows.
AB  - The purpose of this study was to determine the effects of conjugated linoleic
      acid (CLA), Sterculia foetida oil (STO), and fish oil (FO) on milk yield and
      composition, milk FA profile, Delta(9)-desaturation activity, and mammary
      expression of 2 isoforms of stearoyl-coenzyme A desaturase (SCD-1 and SCD-5) in
      lactating dairy cows. Eight multiparous Holstein cows (69 +/- 13 d postpartum)
      were used in a double 4 * 4 Latin square design with 28-d periods. For the first
      14 d of each period, cows received an abomasal infusion of (1) 406 g of a
      saturated fatty acid (SFA) supplement (112 g of 16:0 + 230 g of 18:0) used as a
      control (CTL), (2) 36 g of a CLA supplement (13.9 g of trans-10,cis-12 18:2) +
      370 g of SFA, (3) 7 g of STO (3.1g of 19:1 cyclo) + 399 g of SFA, or (4) 406 g of
      FO (55.2 g of cis-5,-8,-11,-14,-17 20:5 + 59.3 g of cis-4,-7,-10,-13,-16,-19
      22:6). Infusions were followed by a 14-d washout interval. Compared with CTL, STO
      decreased milk yield from 38.0 to 33.0 kg/d, and increased milk fat concentration
      from 3.79 to 4.45%. Milk fat concentration was also decreased by CLA (2.23%) and
      FO (3.34%). Milk fat yield was not affected by STO (1,475 g/d) compared with CTL
      (1,431 g/d), but was decreased by CLA (774 g/d) and FO (1,186 g/d). Desaturase
      indices for 10:0, 12:0, and 20:0 were decreased, whereas the extent of
      desaturation of 14:0, 16:0, 17:0, and 18:0 was not affected by CLA treatment
      compared with CTL. Infusion of STO significantly decreased all calculated
      desaturase indices compared with CTL; the 14:0 index was reduced by 80.7%.
      Infusion of FO decreased the desaturase indices for 10:0, 14:0, 20:0, trans-11
      18:1, and 18:0. The effect of FO on the 14:0 index indicates a decrease in
      apparent Delta(9)-desaturase activity of 30.2%. Compared with CTL, mammary mRNA
      abundance of SCD-1 was increased by STO (+30%) and decreased by CLA (-24%),
      whereas FO had no effect. No effect was observed on mRNA abundance of SCD-5. In
      conclusion, abomasal infusion of CLA, STO, and FO were shown to exhibit varying
      and distinct effects on desaturase indices, an indicator of apparent SCD
      activity, and mammary mRNA abundance of SCD-1.

PMID- 25064650
TI  - Effect of KCl substitution on bacterial viability of Escherichia coli (ATCC
      25922) and selected probiotics.
AB  - Excessive intake of NaCl has been associated with the increased risk of several
      diseases, particularly hypertension. Strategies to reduce sodium intake include
      substitution of NaCl with other salts, such as KCl. In this study, the effects of
      NaCl reduction and its substitution with KCl on cell membranes of a cheese
      starter bacterium (Lactococcus lactis ssp. lactis), probiotic bacteria
      (Bifidobacterium longum, Lactobacillus acidophilus, and Lactobacillus casei), and
      a pathogenic bacterium (Escherichia coli) were investigated using Fourier
      transform infrared (FTIR) spectroscopy. A critical NaCl concentration that
      inhibited the viability of E. coli without affecting the viability of probiotic
      bacteria significantly was determined. To find the critical NaCl concentration,
      de Man, Rogosa, and Sharpe (MRS) broth was supplemented with a range of NaCl
      concentrations [0 (control), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, and
      5.0%], and the effect on cell viability and FTIR spectra was monitored for all
      bacteria. A NaCl concentration of 2.5% was found to be the critical level of NaCl
      to inhibit E. coli without significantly affecting the viability of most of the
      probiotic bacteria and the cheese starter bacterium. The FTIR spectral analysis
      also highlighted the changes that occurred mainly in the amide regions upon
      increasing the NaCl concentration from 2.5 to 3.0% in most of the bacteria.
      Escherichia coli and B. longum were more sensitive to substitution of NaCl with
      KCl, compared with Lb. acidophilus, Lb. casei, and Lc. lactis ssp. lactis. To
      evaluate the effect of substitution of NaCl with KCl, substitution was carried
      out at the critical total salt concentration (2.5%, wt/vol) at varying
      concentrations (0, 25, 50, 75, and 100% KCl). The findings suggest that 50%
      substitution of NaCl with KCl, at 2.5% total salt, could inhibit E. coli without
      affecting the probiotic bacteria. 

PMID- 25064651
TI  - Export competitiveness of dairy products on global markets: the case of the
      European Union countries.
AB  - This paper analyzed the export competitiveness of dairy products of the European
      Union (EU) countries (EU-27) on intra-EU, extra-EU, and global markets, using the
      revealed comparative advantage index over the 2000-2011 period. The results
      indicated that about half of the EU-27 countries have had competitive exports in
      a certain segment of dairy products. The results differed by level of milk
      processing and for intra-EU and extra-EU markets, and did so over the analyzed
      years. Belgium, Denmark, France, Ireland, and the Netherlands are old EU-15
      countries with competitive dairy exports (from the lowest to the highest
      according to the level of milk processing). The majority of the new EU-12
      countries have faced difficulties in maintaining their level of export
      competitiveness, at least for some dairy products and market segments. The more
      competitive EU-12 countries in dairy exports were the Baltic States (Estonia,
      Latvia, and Lithuania) and Poland. The duration of export competitiveness
      differed across the dairy groups of products according to the level of milk
      processing, indicating the importance of dairy chain product differentiation for
      export competitiveness and specialization. The export competitiveness of the
      higher level of processed milk products for final consumption can be significant
      for export dairy chain competitiveness on global markets. 

PMID- 25064652
TI  - Effects of metal ions on growth, beta-oxidation system, and thioesterase activity
      of Lactococcus lactis.
AB  - The effects of divalent metal ions (Ca(2+), Mg(2+), Fe(2+), and Cu(2+)) on the
      growth, beta-oxidation system, and thioesterase activity of Lactococcus lactis
      were investigated. Different metal ions significantly influenced the growth of L.
      lactis: Ca(2+) and Fe(2+) accelerated growth, whereas Cu(2+) inhibited growth.
      Furthermore, Mg(2+) inhibited growth of L. lactis at a low concentration but
      stimulated growth of L. lactis at a high concentration. The divalent metal ions
      had significant effects on activity of the 4 key enzymes of the beta-oxidation
      system (acyl-CoA dehydrogenase, enoyl-CoA hydratase, L-3-hydroxyacyl-CoA
      dehydrogenase, and thiolase) and thioesterase of L. lactis. The activity of acyl
      CoA dehydrogenases increased markedly in the presence of Ca(2+) and Mg(2+),
      whereas it decreased with 1 mmol/L Fe(2+) or 12 mmol/L Mg(2+). All the metal ions
      could induce activity of enoyl-CoA hydratase. In addition, 12 mmol/L Mg(2+)
      significantly stimulated activity of L-3-hydroxyacyl-CoA dehydrogenase, and all
      metal ions could induce activity of thiolase, although thiolase activity
      decreased significantly when 0.05 mmol/L Cu(2+) was added into M17 broth.
      Inhibition of thioesterase activity by all 4 metal ions could be reversed by 2
      mmol/L Ca(2+). These results help us understand the effect of metal ions on the
      beta-oxidation system and thioesterase activity of Lactococcus lactis.

PMID- 25064654
TI  - Associations between calf mortality during days 1 to 90 and herd-level cow and
      production variables in large Swedish dairy herds.
AB  - The aim of the study was to describe large Swedish dairy herds with high and low
      mortality risk in calves during the first 90 d of life, using herd-level data,
      and to evaluate if high calf mortality risk is associated with other herd-level
      management variables that influence cow health. A total of 57 Swedish dairy herds
      met the inclusion criteria of affiliation to the Swedish official milk recording
      scheme, herd size of >=140 and >=160 cows in 2008/2009 and 2009/2010, and calf
      mortality risks, classified as high (HM; calf mortality risk at least 3.5% in
      2008/2009 and 5.5% in 2009/2010; n=28) or low (LM; calf mortality risk less than
      <1.5% in 2008/2009 and 2009/2010; n=29), and were thus included in the study. The
      data used in this study were collected from the Swedish Dairy association during
      the milking year 2009/2010. For LM herds, the calf mortality risk ranged from 0
      to 1.46 (median=0.66) in 2008/2009 and from 0 to 1.48 (median=0.67) in 2009/2010.
      For HM herds, the calf mortality risk ranged from 3.57 to 11.52 (median=6.15) in
      2008/2009 and from 5.88 to 18.23 (median=8.39) in 2009/2010. Median age at death
      was 28 d for HM and 37 d for LM herds. Associations between type of herd (HM or
      LM) and the production variables were evaluated using multi-correspondence
      analysis and logistic regression models covering the areas "mortality and
      culling," "health," "herd/production variables," and "fertility." Herds with HM
      risks during d 1 to 90 were associated with higher on-farm mortality rate in
      cows, lower average milk yield, higher incidence of antibiotic treatment, and a
      higher proportion of purchased animals. These results indicate that herds with HM
      risk during d 1 to 90 have coexisting issues concerning cow management and
      health. Future research is needed to evaluate if identifying HM herds and working
      with advisory and preventive manners at these herds also can be positive for a
      reduction of on-farm mortality and antibiotic usage, which are important issues
      from a global perspective. 

PMID- 25064653
TI  - Postpartum responses of dairy cows supplemented with n-3 fatty acids for
      different durations during the peripartal period.
AB  - The objective of this study was to determine the effect of different durations of
      n-3 supplementation during the peripartal period on production and reproduction
      performance of Holstein dairy cows. Thirty-two Holstein dry cows (16 multiparous
      and 16 primiparous) were blocked within parity for similar expected calving dates
      8 wk before calving. Cows within blocks were assigned randomly to 1 of 4
      treatments: (1) control without n-3 fatty acid (FA) supplementation during the
      dry period; (2) n-3 FA supplementation during the whole dry period (8 wk); and
      (3) n-3 FA supplementation during the early dry period (first 5 wk; far-off), or
      (4) n-3 FA supplementation during the late dry period (last 3 wk; close-up). All
      cows received the same diet without n-3 FA after calving for the first 6 wk of
      lactation. Ovaries of each cow were examined 10, 17, 24, and 34 d from calving
      (calving=d 0) by transrectal ultrasonography to determine follicular development.
      Blood samples were collected at 14-d intervals starting on the first day of the
      dry period (8 wk before expected calving) to determine plasma concentrations of
      glucose, beta-hydroxybutyrate, nonesterified fatty acids, urea N, aspartate
      aminotransferase, and insulin. Blood samples were also collected on d 1, 10, 17,
      24, 31, and 38 postpartum for determination of progesterone concentration. Milk
      yield was recorded daily throughout the experiment and samples were taken twice
      weekly (Monday and Thursday mornings) for analysis of fat, protein, and lactose.
      Yields of milk and 4% fat-corrected milk and milk composition were similar among
      treatments except for fat proportion, which tended to be lower in cows that were
      fed n-3 FA throughout the dry period. We observed no differences among treatments
      for plasma concentrations of metabolites and hormones. The cows that were fed in
      the 3 n-3 FA treatments had larger ovulatory follicles compared with those fed
      the controlled diet. Treatments did not differ significantly in terms of the
      number of days open, day to first service, or number of services per pregnancy.
      In conclusion, n-3 FA supplementation throughout the dry period or in the early
      or late prepartal period had no carryover reproductive postpartum benefits and no
      effect on the production of Holstein dairy cows. 

PMID- 25064655
TI  - Clinical disease and stage of lactation influence shedding of Mycobacterium avium
      subspecies paratuberculosis into milk and colostrum of naturally infected dairy
      cows.
AB  - Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of Johne's
      disease (JD). One mode of transmission of MAP is through ingestion of
      contaminated milk and colostrum by susceptible calves. The objective of this
      study was to determine if the amount of MAP shed into the milk and colostrum of
      infected cows was affected by severity of infection as well as the number of days
      in milk (DIM). Milk was collected over the 305-d lactation period from naturally
      infected cows in the asymptomatic subclinical (n=39) and symptomatic clinical
      (n=29) stages of disease, as well as 8 noninfected control cows. All milk samples
      were assayed for MAP by culture on Herrold's egg yolk medium and either BACTEC
      12B (Becton Dickinson, Franklin Lakes, NJ) or para-JEM (Thermo Fisher Scientific,
      Trek Diagnostic Systems Inc., Cleveland, OH) liquid medium, and by direct PCR for
      the IS900 target gene. Mycobacterium avium ssp. paratuberculosis was detected in
      3.8, 4.1, and 12.6% of milk samples collected from cows with subclinical JD after
      culture in Herrold's egg yolk medium, liquid medium, and direct PCR,
      respectively. The frequency of MAP positivity increased to 12.9, 18.4, and 49.2%
      of milk samples collected from cows with clinical JD by these same methods,
      respectively. None of the milk samples collected from control cows was positive
      for MAP by any detection method. Viable MAP was primarily isolated from milk and
      colostrum of subclinically and clinically infected cows collected in early
      lactation (DIM 0-60), with negligible positive samples observed in mid (DIM 60
      240) and late (DIM 240-305) lactation. This study demonstrates that shedding of
      MAP into milk is affected by infection status of the cow as well as stage of
      lactation, providing useful information to producers to help break the cycle of
      infection within a herd. 

PMID- 25064656
TI  - Microbiota characterization of a Belgian protected designation of origin cheese,
      Herve cheese, using metagenomic analysis.
AB  - Herve cheese is a Belgian soft cheese with a washed rind, and is made from raw or
      pasteurized milk. The specific microbiota of this cheese has never previously
      been fully explored and the use of raw or pasteurized milk in addition to
      starters is assumed to affect the microbiota of the rind and the heart. The aim
      of the study was to analyze the bacterial microbiota of Herve cheese using
      classical microbiology and a metagenomic approach based on 16S ribosomal DNA
      pyrosequencing. Using classical microbiology, the total counts of bacteria were
      comparable for the 11 samples of tested raw and pasteurized milk cheeses,
      reaching almost 8 log cfu/g. Using the metagenomic approach, 207 different
      phylotypes were identified. The rind of both the raw and pasteurized milk cheeses
      was found to be highly diversified. However, 96.3 and 97.9% of the total
      microbiota of the raw milk and pasteurized cheese rind, respectively, were
      composed of species present in both types of cheese, such as Corynebacterium
      casei, Psychrobacter spp., Lactococcus lactis ssp. cremoris, Staphylococcus
      equorum, Vagococcus salmoninarum, and other species present at levels below 5%.
      Brevibacterium linens were present at low levels (0.5 and 1.6%, respectively) on
      the rind of both the raw and the pasteurized milk cheeses, even though this
      bacterium had been inoculated during the manufacturing process. Interestingly,
      Psychroflexus casei, also described as giving a red smear to Raclette-type
      cheese, was identified in small proportions in the composition of the rind of
      both the raw and pasteurized milk cheeses (0.17 and 0.5%, respectively). In the
      heart of the cheeses, the common species of bacteria reached more than 99%. The
      main species identified were Lactococcus lactis ssp. cremoris, Psychrobacter
      spp., and Staphylococcus equorum ssp. equorum. Interestingly, 93 phylotypes were
      present only in the raw milk cheeses and 29 only in the pasteurized milk cheeses,
      showing the high diversity of the microbiota. Corynebacterium casei and
      Enterococcus faecalis were more prevalent in the raw milk cheeses, whereas
      Psychrobacter celer was present in the pasteurized milk cheeses. However, this
      specific microbiota represented a low proportion of the cheese microbiota. This
      study demonstrated that Herve cheese microbiota is rich and that pasteurized milk
      cheeses are microbiologically very close to raw milk cheeses, probably due to the
      similar manufacturing process. The characterization of the microbiota of this
      particular protected designation of origin cheese was useful in enabling us to
      gain a better knowledge of the bacteria responsible for the character of this
      cheese. 

PMID- 25064657
TI  - Associations between age at first calving, rearing average daily weight gain,
      herd milk yield and dairy herd production, reproduction, and profitability.
AB  - The objective of this study was to evaluate the associations of variable
      intensity in rearing dairy heifers on 33 commercial dairy herds, including 23,008
      cows and 18,139 heifers, with age at first calving (AFC), average daily weight
      gain (ADG), and milk yield (MY) level on reproduction traits and profitability.
      Milk yield during the production period was analyzed relative to reproduction and
      economic parameters. Data were collected during a 1-yr period (2011). The farms
      were located in 12 regions in the Czech Republic. The results show that those
      herds with more intensive rearing periods had lower conception rates among
      heifers at first and overall services. The differences in those conception rates
      between the group with the greatest ADG (>=0.800 kg/d) and the group with the
      least ADG (<=0.699 kg/d) were approximately 10 percentage points in favor of the
      least ADG. All the evaluated reproduction traits differed between AFC groups.
      Conception at first and overall services (cows) was greatest in herds with AFC
      >=800 d. The shortest days open (105 d) and calving interval (396 d) were found
      in the middle AFC group (799 to 750 d). The highest number of completed
      lactations (2.67) was observed in the group with latest AFC (>=800 d). The
      earliest AFC group (<=749 d) was characterized by the highest depreciation costs
      per cow at 8,275 Czech crowns (US$414), and the highest culling rate for cows of
      41%. The most profitable rearing approach was reflected in the middle AFC (799 to
      750 d) and middle ADG (0.799 to 0.700 kg) groups. The highest MY (>=8,500 kg)
      occurred with the earliest AFC of 780 d. Higher MY led to lower conception rates
      in cows, but the highest MY group also had the shortest days open (106 d) and a
      calving interval of 386 d. The same MY group had the highest cow depreciation
      costs, net profit, and profitability without subsidies of 2.67%. We conclude that
      achieving low AFC will not always be the most profitable approach, which will
      depend upon farm-specific herd management. The MY is a very important factor for
      dairy farm profitability. The group of farms having the highest MY achieved the
      highest net profit despite having greater fertility problems.

PMID- 25064658
TI  - Salivary alcohol dehydrogenase in non-smoking and smoking alcohol-dependent
      persons.
AB  - Increasing attention to the importance of saliva testing is not surprising
      because smoking and alcohol drinking act synergistically on oral tissues, and
      their metabolite levels, e.g., acetaldehyde, are much higher in saliva than in
      blood. The activity of salivary alcohol dehydrogenase (ADH) comes from oral
      microbiota, mucosa, and salivary glands. The purpose of this study was to
      investigate the involvement of ADH in the oral health pathology of smoking (AS)
      and non-smoking (ANS) alcohol-dependent males. The results indicated that the AS
      group had a more significant and longer duration (until the 30th day of alcohol
      abstinence) decrease in ADH activity and output than the ANS group (until the
      15th day of alcohol abstinence) compared to controls (social drinkers; C). The
      decreased salivary flow (SF) in alcoholics was observed longer in the ANS group
      (until the 30th day of alcohol abstinence), whereas in the AS group SF normalized
      at the 15th day, probably due to the irritating effect of tobacco smoke on the
      oral mucosa. Because saliva was centrifuged to remove cells and debris (including
      microbial cells), the detected salivary ADH activity was derived from salivary
      glands and/or oral mucosa. A more profound and longer decrease in ADH
      activity/output in smoking than non-smoking alcoholics was likely due to the
      damaged salivary glands and/or oral mucosa, caused by the synergistic effect of
      alcohol drinking and smoking. The lower values of salivary ADH in smoking than
      non-smoking alcoholics might also be partly due to the reversed/inhibited ADH
      reaction by high levels of accumulated acetaldehyde. 

PMID- 25064659
TI  - Mathematical modelling of cancer invasion: implications of cell adhesion
      variability for tumour infiltrative growth patterns.
AB  - Cancer invasion, recognised as one of the hallmarks of cancer, is a complex,
      multiscale phenomenon involving many inter-related genetic, biochemical, cellular
      and tissue processes at different spatial and temporal scales. Central to
      invasion is the ability of cancer cells to alter and degrade an extracellular
      matrix. Combined with abnormal excessive proliferation and migration which is
      enabled and enhanced by altered cell-cell and cell-matrix adhesion, the cancerous
      mass can invade the neighbouring tissue. Along with tumour-induced angiogenesis,
      invasion is a key component of metastatic spread, ultimately leading to the
      formation of secondary tumours in other parts of the host body. In this paper we
      explore the spatio-temporal dynamics of a model of cancer invasion, where cell
      cell and cell-matrix adhesion is accounted for through non-local interaction
      terms in a system of partial integro-differential equations. The change of
      adhesion properties during cancer growth and development is investigated here
      through time-dependent adhesion characteristics within the cell population as
      well as those between the cells and the components of the extracellular matrix.
      Our computational simulation results demonstrate a range of heterogeneous
      dynamics which are qualitatively similar to the invasive growth patterns observed
      in a number of different types of cancer, such as tumour infiltrative growth
      patterns (INF). 

PMID- 25064660
TI  - RETRACTED: Identifying halophilic proteins based on random forests with
      preprocessing of the pseudo-amino acid composition.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). This article has been
      retracted at the request of the authors. When using the resampling method to
      preprocess the raw data of the paper used, some of the types of the proteins
      (i.e., the HI, HO and NP) were changed; thus, the predicting accuracy cannot
      reflect the real results. This means the effectiveness of resampling methods in
      this article gives false results. The Publisher apologizes for any inconvenience
      this may cause. 

PMID- 25064662
TI  - Spine intervention.

PMID- 25064661
TI  - Magnitude of influenza virus replication and cell damage is associated with
      interleukin-6 production in primary cultures of human tracheal epithelium.
AB  - Primary cultures of human tracheal epithelium were infected with influenza
      viruses to examine the relationships between the magnitude of viral replication
      and infection-induced cell damage and cytokine production in airway epithelial
      cells. Infection with four strains of the type A influenza virus increased the
      detached cell number and lactate dehydrogenase (LDH) levels in the supernatants.
      The detached cell number and LDH levels were related to the viral titers and
      interleukin (IL)-6 levels and the nuclear factor kappa B (NF-kappaB) p65
      activation. Treatment of the cells with an anti-IL-6 receptor antibody and an NF
      kappaB inhibitor, caffeic acid phenethyl ester, reduced the detached cell number,
      viral titers and the LDH levels and improved cell viability after infection with
      the pandemic influenza virus [A/Sendai-H/N0633/2009 (H1N1) pdm09]. A caspase-3
      inhibitor, benzyloxycarbonyl-DEVD-fluoromethyl ketone, reduced the detached cell
      number and viral titers. Influenza viral infection-induced cell damage may be
      partly related to the magnitude of viral replication, NF-kappaB-p65-mediated IL-6
      production and caspase-3 activation. 

PMID- 25064663
TI  - Incidental adrenal lesions detected on enhanced abdominal dual-energy CT: can the
      diagnostic workup be shortened by the implementation of virtual unenhanced
      images?
AB  - OBJECTIVE: To determine whether post-processing of the data from portal-phase
      enhanced dual-energy CT (DECT), with or without the addition of a late enhanced
      phase acquisition, may enable characterization of adrenal lesions without the
      need for acquisition of pre-contrast images. MATERIALS AND METHODS: Twenty-two
      patients with 24 adrenal lesions underwent unenhanced, venous and delayed phase
      DECT. Of these lesions, 20 were found to be adrenal adenomas, on the basis of
      histopathology, unenhanced attenuation values between 0 and -10 HU, or stability
      over at least 6 months. For all 24 lesions, true and virtual unenhanced
      attenuation values were measured based on the data of the portal (VNCp) and the
      delayed (VNCd) DECT acquisition. The absolute washout values based on the true
      non-contrast (TNC) and the VNCp and VNCd image series were also measured. The
      washout was also calculated based on the iodine concentration measured from both
      contrast-enhanced acquisitions. RESULTS: Mean virtual unenhanced attenuation
      values of all lesions calculated from the portal phase images was 12.6 HU, and
      was 4.02 HU higher than the values based on true unenhanced images (p=0.020).
      Washout values calculated from virtual unenhanced attenuation based on the VNCp
      were also significantly different (p=0.0304) while those calculated from VNCd and
      from iodine concentration correlated with the corresponding values based on the
      true unenhanced values (p>0.999). CONCLUSIONS: Our data indicate that attenuation
      values of adrenal adenomas based on virtual unenhanced images are significantly
      higher than those obtained with true unenhanced images. An incidental adrenal
      lesion with a virtual unenhanced attenuation lower than 10 HU can thus be safely
      characterized as an adenoma.

PMID- 25064664
TI  - Mismatch Negativity reduction in the left cortical regions in first-episode
      psychosis and in individuals at ultra high-risk for psychosis.
AB  - Mismatch Negativity (MMN), an electrophysiological component that represents
      sensory memory processing, has been proposed as a potential vulnerability marker
      for psychosis. Some studies have reported a more evident MMN amplitude reduction
      in the left cortical regions in patients with schizophrenia. Little is known
      about this asymmetric pattern in patients in their first episode of psychosis
      (FEP) and individuals at ultra-high risk for psychosis (UHR). The aim of this
      study was to explore the scalp distribution of MMN in 20 FEP patients, 20 UHR
      subjects and 23 healthy controls. Both clinical groups were antipsychotic naive.
      MMN was obtained during a passive auditory paradigm with duration deviant tones
      and analyzed from 15 frontocentral electrodes. There was a significant group
      effect in MMN amplitude (F=3.4, p=0.04), showing a decrement in both FEP and UHR
      compared to controls (FEP mean difference (MD)=-0.48, p=0.02; UHR MD=-0.44,
      p=0.04), and this amplitude decrement was more evident in the left middle regions
      for both clinical groups (p<0.01). In conclusion, we found a clear amplitude
      reduction of duration MMN in FEP patients and UHR individuals, especially in the
      left cortical regions. The observed pattern in both clinical samples supports the
      notion that MMN could be a vulnerability marker for psychosis. We propose to
      continue the study of this MMN laterality effect in future longitudinal studies. 

PMID- 25064665
TI  - Sex differences in the relationship between white matter connectivity and
      creativity.
AB  - Creative cognition emerges from a complex network of interacting brain regions.
      This study investigated the relationship between the structural organization of
      the human brain and aspects of creative cognition tapped by divergent thinking
      tasks. Diffusion weighted imaging (DWI) was used to obtain fiber tracts from 83
      segmented cortical regions. This information was represented as a network and
      metrics of connectivity organization, including connectivity strength, clustering
      and communication efficiency were computed, and their relationship to individual
      levels of creativity was examined. Permutation testing identified significant sex
      differences in the relationship between global connectivity and creativity as
      measured by divergent thinking tests. Females demonstrated significant inverse
      relationships between global connectivity and creative cognition, whereas there
      were no significant relationships observed in males. Node specific analyses
      revealed inverse relationships across measures of connectivity, efficiency,
      clustering and creative cognition in widespread regions in females. Our findings
      suggest that females involve more regions of the brain in processing to produce
      novel ideas to solutions, perhaps at the expense of efficiency (greater path
      lengths). Males, in contrast, exhibited few, relatively weak positive
      relationships across these measures. Extending recent observations of sex
      differences in connectome structure, our findings of sexually dimorphic
      relationships suggest a unique topological organization of connectivity
      underlying the generation of novel ideas in males and females. 

PMID- 25064666
TI  - Supplementary motor area activations predict individual differences in temporal
      change sensitivity and its illusory distortions.
AB  - Perception of time and temporal change is critical for human cognition. Yet,
      perception of temporal change is susceptible to contextual influences such as
      changes of a sound's pitch. Using functional magnetic resonance imaging (fMRI),
      the current study aimed to investigate perception of temporal rate change and
      pitch-induced illusory distortions. In a 6 * 6 design, human participants (N=19)
      listened to frequency-modulated sounds (~ 4 Hz) that varied over time in both
      modulation rate and pitch. Participants judged the direction of rate change
      ('speeding up' vs. 'slowing down'), while ignoring changes in pitch.
      Behaviorally, rate judgments were strongly biased by pitch changes: Participants
      perceived rate to slow down when pitch decreased and to speed up when pitch
      increased ('rate-change illusion'). The fMRI data revealed activation increases
      with increasing task difficulty in pre-SMA, left putamen, and right IFG/insula.
      Importantly, activation in pre-SMA was linked to the perceptual sensitivity to
      discriminate rate changes and, together with the left putamen, to relative
      reductions in susceptibility to pitch-induced illusory distortions. Right
      IFG/insula activations, however, only scaled with task difficulty. These data
      offer a distinction between regions whose activations scale with perceptual
      sensitivity to features of time (pre-SMA) and those that more generally support
      behaving in difficult listening conditions (IFG/insula). Hence, the data
      underscore that individual differences in time perception can be related to
      different patterns of neurofunctional activation.

PMID- 25064667
TI  - Tracing the evolution of multi-scale functional networks in a mouse model of
      depression using persistent brain network homology.
AB  - Many brain diseases or disorders, such as depression, are known to be associated
      with abnormal functional connectivity in neural networks in the brain. Some
      bivariate measures of electroencephalography (EEG) for coupling analysis have
      been used widely in attempts to explain abnormalities related with depression.
      However, brain network evolution based on persistent functional connections in
      EEG signals could not be easily unveiled. For a geometrical exploration of brain
      network evolution, here, we used persistent brain network homology analysis with
      EEG signals from a corticosterone (CORT)-induced mouse model of depression. EEG
      signals were obtained from eight cortical regions (frontal, somatosensory,
      parietal, and visual cortices in each hemisphere). The persistent homology
      revealed a significantly different functional connectivity between the control
      and CORT model, but no differences in common coupling measures, such as cross
      correlation and coherence, were apparent. The CORT model showed a more localized
      connectivity and decreased global connectivity than the control. In particular,
      the somatosensory and parietal cortices were loosely connected in the CORT model.
      Additionally, the CORT model displayed altered connections among the cortical
      regions, especially between the frontal and somatosensory cortices, versus the
      control. This study demonstrates that persistent homology is useful for brain
      network analysis, and our results indicate that the CORT-induced depression mouse
      model shows more localized and decreased global connectivity with altered
      connections, which may facilitate characterization of the abnormal brain network
      underlying depression. 

PMID- 25064668
TI  - Differentiating BOLD and non-BOLD signals in fMRI time series from anesthetized
      rats using multi-echo EPI at 11.7 T.
AB  - The study of spontaneous brain activity using fMRI is central to mapping brain
      networks. However, current fMRI methodology has limitations in the study of small
      animal brain organization using ultra-high field fMRI experiments, as imaging
      artifacts are difficult to control and the relationship between classical
      neuroanatomy and spontaneous functional BOLD activity is not fully established.
      Challenges are especially prevalent during the fMRI study of individual rodent
      brains, which could be instrumental to studies of disease progression and
      pharmacology. A recent advance in fMRI methodology enables unbiased, accurate,
      and comprehensive identification of functional BOLD signals by interfacing multi
      echo (ME) fMRI acquisition, NMR signal decay analysis, and independent components
      analysis (ICA), in a procedure called ME-ICA. Here we present a pilot study on
      the suitability of ME-ICA for ultra high field animal fMRI studies of spontaneous
      brain activity under anesthesia. ME-ICA applied to 11.7 T fMRI data of rats first
      showed robust performance in automatic high dimensionality estimation and ICA
      decomposition, similar to that previously reported for 3.0 T human data. ME
      sequence optimization for 11.7 T indicated that 3 echoes, 0.5mm isotropic voxel
      size and TR=3s was adequate for sensitive and specific BOLD signal acquisition.
      Next, in seeking optimal inhaled isoflurane anesthesia dosage, we report that
      progressive increase in anesthesia goes with concomitant decrease in statistical
      complexity of "global" functional activity, as measured by the number of BOLD
      components, or degrees of freedom (DOF). Finally, BOLD functional connectivity
      maps for individual rodents at the component level show that spontaneous BOLD
      activity follows classical neuroanatomy, and seed-based analysis shows plausible
      cortical-cortical and cortical-subcortical functional interactions.

PMID- 25064669
TI  - Nutritional influences on early white matter development: response to Anderson
      and Burggren.
AB  - Does breastfeeding alter early brain development? In a recent retrospective
      study, our group examined the cross-sectional relationship between early infant
      feeding practice and white matter maturation and cognitive development. In groups
      matched for child and mother age, gestation duration, birth weight, gender
      distribution, and socio-economic status; we observed that children who were
      breastfed exclusively for at least 3 months showed, on average, increased white
      matter myelin development compared to children who either were exclusively
      formula-fed, or received a mixture of breast milk and formula. In secondary
      analysis on sub-sets of these children, again matched for important confounding
      variables, we found improved cognitive test scores of receptive language in the
      exclusively breast-fed children compared to formula or formula+breast-fed
      children; and that prolonged breastfeeding was associated with increased motor,
      language, and visual functioning in exclusively breast-fed children. In response
      to this work, Anderson and Burggren have questioned our methodology and, by
      association, our findings. Further, they use their critique as a platform for
      advancing an alternative interpretation of our findings: that observed results
      were not associated with prolonged breast-feeding, but rather delayed the
      introduction of cow's milk. In this response, we address and clarify some of the
      misconceptions presented by Anderson and Burggren.

PMID- 25064670
TI  - NMR-based molecular ruler for determining the depth of intercalants within the
      lipid bilayer: Part III: studies on keto esters and acids.
AB  - The development of "molecular rulers" would allow one to quantitatively locate
      the penetration depth of intercalants within lipid bilayers. To this end, an
      attempt was made to correlate the (13)C NMR chemical shift of polarizable
      "reporter" carbons (e.g., carbonyls) of intercalants within DMPC liposomal
      bilayers - with the polarity it experiences, and with its Angstrom distance from
      the interface. This requires families of molecules with two "reporter carbons"
      separated by a known distance, residing at various depths/polarities within the
      bilayer. For this purpose, two homologous series of dicarbonyl compounds, methyl
      n-oxooctadecanoates and the corresponding n-oxooctadecanoic acids (n=4-16), were
      synthesized. To assist in assignment and detection several homologs in each
      system were prepared (13)C-enriched in both carbonyls. Within each family, the
      number of carbons and functional groups remains the same, with the only
      difference being the location of the second ketone carbonyl along the fatty acid
      chain. Surprisingly, the head groups within each family are not anchored near the
      lipid-water interface, nor are they even all located at the same depth.
      Nevertheless, using an iterative best fit analysis of the data points enables one
      to obtain an exponential curve. The latter gives substantial insight into the
      correlation between polarity (measured in terms of the Reichardt polarity
      parameter, ET(30)) and penetration depth into the liposomal bilayer. Still
      missing from this curve are data points in the moderate polarity range. 

PMID- 25064671
TI  - Are clusters of dietary patterns and cluster membership stable over time? Results
      of a longitudinal cluster analysis study.
AB  - INTRODUCTION: Developing nutrition education interventions based on clusters of
      dietary patterns can only be done adequately when it is clear if distinctive
      clusters of dietary patterns can be derived and reproduced over time, if cluster
      membership is stable, and if it is predictable which type of people belong to a
      certain cluster. Hence, this study aimed to: (1) identify clusters of dietary
      patterns among Dutch adults, (2) test the reproducibility of these clusters and
      stability of cluster membership over time, and (3) identify sociodemographic
      predictors of cluster membership and cluster transition. METHODS: This study had
      a longitudinal design with online measurements at baseline (N=483) and 6 months
      follow-up (N=379). Dietary intake was assessed with a validated food frequency
      questionnaire. A hierarchical cluster analysis was performed, followed by a K
      means cluster analysis. Multinomial logistic regression analyses were conducted
      to identify the sociodemographic predictors of cluster membership and cluster
      transition. RESULTS: At baseline and follow-up, a comparable three-cluster
      solution was derived, distinguishing a healthy, moderately healthy, and unhealthy
      dietary pattern. Male and lower educated participants were significantly more
      likely to have a less healthy dietary pattern. Further, 251 (66.2%) participants
      remained in the same cluster, 45 (11.9%) participants changed to an unhealthier
      cluster, and 83 (21.9%) participants shifted to a healthier cluster. Men and
      people living alone were significantly more likely to shift toward a less healthy
      dietary pattern. CONCLUSIONS: Distinctive clusters of dietary patterns can be
      derived. Yet, cluster membership is unstable and only few sociodemographic
      factors were associated with cluster membership and cluster transition. These
      findings imply that clusters based on dietary intake may not be suitable as a
      basis for nutrition education interventions.

PMID- 25064672
TI  - Effects of daily consumption of one or varied peanut flavors on acceptance and
      intake.
AB  - To realize the health benefits associated with peanut consumption, it is
      important that they remain acceptable with regular intake. Peanuts are marketed
      with various flavorings so that consumers will not become fatigued by frequent
      consumption of any single flavor. This study sought to determine whether liking
      of peanuts or compliance to a peanut feeding intervention would differ based on
      receiving an individual flavor or a variety of flavors. Participants (n=151) were
      directed to consume 42 g peanuts/d for 12 weeks as 14-g servings of 3 different
      flavors (n=50) or a single flavor (n=25-26/group). The trial was randomized, with
      a parallel-group design. Neither the peanut flavor consumed nor the presence of
      variety had an impact on liking of the peanuts or compliance with the study
      protocol (p>0.05). Men had significantly greater compliance and liking ratings
      than women (p<0.05), but liking declines did not differ based on sex. Eating
      attitudes and dietary restraint did not correlate with liking or compliance.
      Peanuts were generally well-liked in the study, with a mean liking of 69 on a 100
      mm visual analogue scale and a decrease of less than 15% over 12 weeks. Overall
      compliance to the protocol was 96.9%, suggesting participants were able to
      incorporate peanuts into their diet on a daily basis. These findings suggest a
      recommendation to regularly consume peanuts would be well-tolerated, facilitating
      their contribution to a healthy diet. The study was conducted between February
      2010 and May 2012 at Purdue University, West Lafayette, IN, USA. This trial was
      registered at clinicaltrials.gov as NCT01886326.

PMID- 25064673
TI  - Renal leukocyte chemotactic factor 2 (LECT2) amyloidosis in First Nations people
      in Northern British Columbia, Canada: a report of 4 cases.
AB  - Leukocyte chemotactic factor 2 (LECT2) amyloidosis is a recently identified type
      of amyloidosis that may represent an underdiagnosed cause of chronic kidney
      disease. LECT2 amyloidosis typically is reported as being renal limited and, in
      the United States, more prevalent in Hispanic patients. We add to the
      epidemiologic data of this condition by describing 4 First Nations people from
      Northern British Columbia, Canada, who presented with slowly progressive chronic
      kidney disease that was found to be due to LECT2 amyloidosis. 

PMID- 25064674
TI  - Visit-to-visit variability in blood pressure and kidney and cardiovascular
      outcomes in patients with type 2 diabetes and nephropathy: a post hoc analysis
      from the RENAAL study and the Irbesartan Diabetic Nephropathy Trial.
AB  - BACKGROUND: Increased systolic blood pressure variability between outpatient
      visits is associated with increased incidence of cardiovascular end points.
      However, few studies have examined the association of visit-to-visit variability
      in systolic blood pressure with clinically relevant kidney disease outcomes. We
      analyzed the association of systolic blood pressure visit-to-visit variability
      with renal and cardiovascular morbidity and mortality among individuals with
      diabetes and nephropathy. STUDY DESIGN: Observational analysis of IDNT
      (Irbesartan Diabetic Nephropathy Trial) and the RENAAL (Reduction of End Points
      in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan)
      Study. SETTING & PARTICIPANTS: 2,739 participants with type 2 diabetes and
      nephropathy with at least 1 year of blood pressure measurements available.
      PREDICTORS: Systolic blood pressure visit-to-visit variability was calculated
      from the SD of the systolic blood pressure from 4 visits occurring 3-12 months
      postrandomization. OUTCOMES: The kidney disease outcome was defined as time to
      confirmed doubling of serum creatinine level, end-stage renal disease, or death;
      the cardiovascular outcome was defined as time to cardiovascular death,
      myocardial infarction, stroke, hospitalization for heart failure, or
      revascularization. RESULTS: Mean visit-to-visit variability in systolic blood
      pressure from 3 to 12 months postrandomization was 12.0+/-6.8(SD)mmHg. Following
      this ascertainment period, there were 954 kidney disease and 542 cardiovascular
      events. Greater systolic blood pressure visit-to-visit variability was associated
      independently with increased risk of the composite kidney disease end point (HR
      per 1-SD increment, 1.08 [95%CI, 1.01-1.16]; P=0.02) and end-stage renal disease,
      but not with the cardiovascular outcome. LIMITATIONS: Observational study with
      the potential for confounding. CONCLUSIONS: In diabetic individuals with
      nephropathy, systolic blood pressure visit-to-visit variability is associated
      independently with hard kidney disease outcomes.

PMID- 25064676
TI  - Drosophila heparan sulfate 3-O sulfotransferase B null mutant is viable and
      exhibits no defects in Notch signaling.
AB  - Heparan sulfate proteoglycans (HSPGs) are critically involved in a variety of
      biological events. The functions of HSPGs are determined by the nature of the
      core proteins and modifications of heparan sulfate (HS) glycosaminoglycan (GAG)
      chains. The distinct O-sulfotransferases are important for nonrandom
      modifications at specific positions. Two HS 3-O sulfotransferase (Hs3st) genes,
      Hs3st-A and Hs3st-B, were identified in Drosophila. Previous experiments using
      RNA interference (RNAi) suggested that Hs3st-B was required for Notch signaling.
      Here, we generated a null mutant of Hs3st-B via ends-out gene targeting and
      examined its role(s) in development. We found that homozygous Hs3st-B mutants
      have no neurogenic defects or alterations in the expression of Notch signaling
      target gene. Thus, our results strongly argue against an essential role for Hs3st
      B in Notch signaling. Moreover, we have generated two independent Hs3st-A RNAi
      lines which worked to deplete Hs3st-A. Importantly, Hs3st-A RNAi combined with
      Hs3st-B mutant flies did not alter the expression of Notch signaling components,
      arguing that both Hs3st-A and Hs3st-B were not essential for Notch signaling. The
      establishment of Hs3st-B mutant and effective Hs3st-A RNAi lines provides
      essential tools for further studies of the physiological roles of Hs3st-A and
      Hs3st-B in development and homeostasis. 

PMID- 25064675
TI  - The E3 ubiquitin ligase gp78 protects against ER stress in zebrafish liver.
AB  - Enhanced endoplasmic reticulum (ER)-associated protein degradation (ERAD)
      activity by the unfolded protein response (UPR) represents one of the mechanisms
      for restoring ER homeostasis. In vitro evidence indicates that the mammalian gp78
      protein is an E3 ubiquitin ligase that facilitates ERAD by polyubiquitinating and
      targeting proteins for proteasomal degradation under both physiologic and stress
      conditions. However, the in vivo function of gp78 in maintaining ER protein
      homeostasis remains untested. Here we show that like its mammalian counterpart,
      the zebrafish gp78 is also an E3 ubiquitin ligase as revealed by in vitro
      ubiquitination assays. Expression analysis uncovered that gp78 is highly
      expressed in several organs, including liver and brain, of both larval and adult
      fish. Treatment of larvae or adult fish with tunicamycin induces ER stress and
      upregulates the expression of several key components of the gp78 ERAD complex in
      the liver. Moreover, liver-specific overexpression of the dominant-negative form
      of gp78 (gp78-R2M) renders liver more sensitive to tunicamycin-induced ER stress
      and enhances the expression of sterol response element binding protein (Srebp)
      target genes, which was largely suppressed in fish overexpressing wild-type gp78.
      Together, these data indicate that gp78 plays a critical role in protecting
      against ER stress in liver. 

PMID- 25064677
TI  - Transcriptomic response to Yersinia pestis: RIG-I like receptor signaling
      response is detrimental to the host against plague.
AB  - Bacterial pathogens have evolved various mechanisms to modulate host immune
      responses for successful infection. In this study, RNA-sequencing technology was
      used to analyze the responses of human monocytes THP1 to Yersinia pestis
      infection. Over 6000 genes were differentially expressed over the 12 h infection.
      Kinetic responses of pathogen recognition receptor signaling pathways, apoptosis,
      antigen processing, and presentation pathway and coagulation system were analyzed
      in detail. Among them, RIG-I-like receptor (RLR) signaling pathway, which was
      established for antiviral defense, was significantly affected. Mice lacking MAVS,
      the adaptor of the RLR signaling pathway, were less sensitive to infection and
      exhibited lower IFN-beta production, higher Th1-type cytokines IFN-gamma and IL
      12 production, and lower Th2-type cytokines IL-4 and IL-13 production in the
      serum compared with wild-type mice. Moreover, infection of pathogenic bacteria
      other than Y. pestis also altered the expression of the RLR pathway, suggesting
      that the response of RLR pathway to bacterial infection is a universal mechanism.

PMID- 25064678
TI  - A matrilineal genetic legacy from the last glacial maximum confers susceptibility
      to schizophrenia in Han Chinese.
AB  - Mitochondrial dysfunction has been widely reported in schizophrenia patients. To
      dissect the matrilineal structure of Han Chinese with or without schizophrenia
      and to decipher the maternal influence and evolutionary history of schizophrenia,
      a total of 1212 schizophrenia patients and 1005 matched healthy controls, all of
      Han Chinese origin, were recruited in Hunan Province, China. We classified
      haplogroup for each individual based on mitochondrial DNA (mtDNA) sequence
      variations and compared the haplogroup distribution pattern between cases and
      controls. Haplogroup B5a presented a higher frequency in cases than in controls
      (P = 0.02, OR = 1.67, 95% CI = [1.09, 2.56]), and this result could be confirmed
      by permutation analysis. Age estimation of haplogroup B5a in cases revealed a
      much younger age than that of controls, which was coincident with the Northern
      Hemisphere deglaciation at the end of the Last Glacial Maximum. Analysis of
      complete mtDNA in five patients belonging to haplogroup B5a showed that this
      background effect might be caused by haplogroup-defining variants m.8584G>A and
      m.10398A>G. Our results showed that matrilineal risk factor for schizophrenia had
      an ancient origin and might acquire a predisposing effect on schizophrenia due to
      the environment change and/or orchestration with other nuclear genetic factors
      appeared recently in human evolutionary history. 

PMID- 25064679
TI  - RNA guided genome editing in mouse germ-line stem cells.

PMID- 25064680
TI  - Genome of Staphylococcus xylosus and comparison with S. aureus and S.
      epidermidis.

PMID- 25064681
TI  - Cost-effectiveness analysis of psychosocial intervention for early stage
      schizophrenia in China: a randomized, one-year study.
AB  - BACKGROUND: A combination of psychosocial interventions and medications has been
      highly recommended as a successful treatment package for schizophrenia. Its cost
      effectiveness has not been fully explored yet. The aim of the present analysis
      was to evaluate the cost-effectiveness of antipsychotics combined with
      psychosocial treatment and treatment as usual for patients with early-stage
      schizophrenia. METHOD: Patients with schizophrenia (N = 1, 268) were assigned to
      the combination of medication and psychosocial intervention or treatment as usual
      for up to 12 months. Cost analysis included direct medical costs, direct
      nonmedical costs and indirect costs. Quality-adjusted life year (QALY) ratings
      were assessed with Short- Form 6D. RESULTS: Average monthly psychosocial
      intervention costs for combined treatment were higher than treatment as usual (p
      = 0.005), but no significant differences were found in direct costs, indirect
      costs, and total costs between two groups (all p-values >= 0.556). Combined
      treatment was associated with significant higher QALY ratings than treatment as
      usual (p = 0.039). Compared with treatment as usual, combined treatment resulted
      in a gain of 0.031 QALY ratings at an additional cost of US$ 56.4, yielding an
      incremental cost-effectiveness ratio of US$ 1819.4 per QALY gained. CONCLUSIONS:
      Despite some limitations, our results supported that medication combined with
      psychosocial treatment was more cost-effective than treatment as usual for
      patients with early-stage schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00654576.

PMID- 25064683
TI  - Classifying Chinese children with dyslexia by dual-route and triangle models of
      Chinese reading.
AB  - This present study focuses on classifying developmental dyslexia by combining two
      famous models, the dual-route model and the triangle model of Chinese reading, re
      examining validity of the subtypes, and observing the error types of word
      recognition for each subtype. Sixty-sixth graders with dyslexia in Chinese and 45
      sixth graders who were matched by age and IQ with the dyslexic group were
      involved in the present study. Twelve (20%) sixth graders from the dyslexic group
      were classified as having phonological dyslexia, 11 (18.3%) were classified as
      surface dyslexia, 12 (20%) were classified as deep dyslexia, and five (8.3%) of
      them were classified as displaying more than one kind of deficit. Besides, still
      more than half (31; 51.7%) of the dyslexic group did not belong to any subtypes
      here. These subtypes had a good validity based on comparison of their
      phonological awareness, orthography, and semantics. Finally, for their error
      types of word recognition, both children with multiple-deficit dyslexia and
      children with non-subtype dyslexia showed a proportional pattern of six kinds of
      errors. Children with phonological dyslexia showed more phonetic errors and
      analogy errors, children with surface dyslexia showed more visual errors and
      analogy errors, and children with deep dyslexia showed more semantic errors and
      selective errors. 

PMID- 25064682
TI  - Eating behavior, prenatal and postnatal growth in Angelman syndrome.
AB  - The objectives of the present study were to investigate eating behavior and
      growth parameters in Angelman syndrome. We included 39 patients with Angelman
      syndrome. Twelve cases had a larger Class I deletion, eighteen had a smaller
      Class II deletion, whereas paternal uniparental disomy (pUPD) or a verified UBE3A
      mutation were present in five and four cases, respectively. Eating behavior was
      assessed by a questionnaire. Anthropometric measures were obtained from medical
      records and compared to Danish reference data. Children with pUPD had
      significantly larger birth weight and birth length than children carrying a
      deletion or a UBE3A mutation. We found no difference in birth weight or length in
      children with Class I or Class II deletions. When maternal birth weight and/or
      birth weight of siblings were taken into consideration, children with Class I
      deletion had a lower weight at birth than expected, and the weight continued to
      be reduced during the investigated initial five years of life. In contrast,
      children with pUPD showed hyperphagic behavior and their weight increased
      significantly after the age of two years. Accordingly, their body mass index was
      significantly increased as compared to children with a deletion. At birth, one
      child showed microcephaly. At five years of age, microcephaly was observed in
      half of the deletion cases, but in none of the cases with a UBE3A mutation or
      pUPD. The apparently normal cranial growth in the UBE3A and pUPD patients should
      however be regarded as the result of a generally increased growth. Eating
      behavior, pre- and postnatal growth in children with Angelman syndrome depends on
      genotype. 

PMID- 25064684
TI  - The chemokine CCL5 induces selective migration of bovine classical monocytes and
      drives their differentiation into LPS-hyporesponsive macrophages in vitro.
AB  - Human and mouse studies indicate distinct roles of selected chemokines for
      monocyte subset attraction. We therefore analyzed the still unknown sensitivity
      and response of bovine monocyte subsets toward two monocyte-attracting chemokines
      (CCL2, CCL5). Only CCL5 induced a significant Ca(2+)influx and migration response
      in bovine monocytes, with classical and intermediate monocytes being
      significantly stimulated and attracted compared to nonclassical monocytes. The
      presence of CCL5 during in vitro macrophage differentiation did not alter their
      capacity to phagocytize or to generate reactive oxygen species upon stimulation
      with E. coli. However, macrophages differentiated in the presence of CCL5
      displayed an altered phenotype with significantly less expressed CD14 and MHC
      class II molecules, whereas CD16 was upregulated. Moreover, CCL5-differentiated
      macrophages displayed a reduced upregulation of CXCL8, ARG1, IL6 and IL10 mRNA.
      Taken together, CCL5 but not CCL2 mainly attract bovine classical monocytes and
      promote their differentiation into LPS-hypo-responsive macrophages.

PMID- 25064685
TI  - Isoforms of the CD79 signal transduction component of the macropod B-cell
      receptor.
AB  - B cell responses and their concomitant signal transduction pathways are not well
      understood in marsupial mammals, despite the availability of gene expression data
      for key immunoglobulin genes and for elements of the CD79a/CD79b heterodimer
      signalling complex for two model marsupials. Broader studies of factors that
      influence B cell responses are still hampered by a lack of species-specific
      reagents and there are few reports of other factors that influence gene
      expression such as the potential for splice variants in BCR components, which may
      influence immune signalling pathways. In this study, we characterise CD79a and
      CD79b genes in the endangered macropod marsupial, Onychogalea fraenata (the
      bridled nailtail wallaby) and show that domains and residues important for the
      structural and functional integrity of both monomers are conserved in this
      species, consistent with results previously reported for the closely-related
      macropod, Macropus eugenii (the tammar wallaby). We extend this work to report
      the detection of splice variants for CD79a and CD79b in wallaby species; three
      CD79a isoforms and one CD79b isoform. Of these, two CD79a isoforms and the CD79b
      isoform have not been reported in any other mammalian species.

PMID- 25064686
TI  - A nationwide cohort study of stage I seminoma patients followed on a surveillance
      program.
AB  - BACKGROUND: Increasing concerns about late effects after adjuvant treatment for
      stage I seminoma have made surveillance an attractive alternative. OBJECTIVE: To
      evaluate the surveillance strategy in a nationwide cohort study. DESIGN, SETTING,
      AND PARTICIPANTS: A retrospective, population-based study of Danish patients
      diagnosed with stage I seminoma between 1984 and 2008 and followed for 5 yr
      (n=1954). Patient data were linked with national registries on November 30, 2012,
      to obtain information on late relapse, vital status, and cause of death. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Disease-specific survival (DSS), overall
      survival, relapse rates, time to relapse, detection of relapse, and prognostic
      factors for relapse were described for the cohort. The Kaplan-Meier method was
      used to determine survival probabilities. A Cox proportional hazards model was
      used for multivariate analysis of prognostic factors. RESULTS AND LIMITATIONS:
      Median follow-up time was 15.1 yr. In total, 369 patients relapsed after a median
      13.7 mo. DSS after 15 yr was 99.3%. Tumor size was a significant factor for
      relapse. Either vascular invasion or invasion of epididymis was significant if
      the other factor was excluded from analysis. Limitations include the
      retrospective nature of the study and the number of missing values in analysis.
      CONCLUSIONS: In the world's largest study of stage I seminoma patients, we found
      surveillance to be a safe alternative to adjuvant therapies. Tumor size was a
      significant factor for relapse, together with either invasion of epididymis or
      vascular invasion. PATIENT SUMMARY: In this nationwide study, we looked at the
      outcomes of patients with stage I seminoma followed for 5 yr. We found that
      surveillance is a safe alternative to adjuvant treatment.

PMID- 25064687
TI  - Percutaneous nephrolithotomy versus retrograde intrarenal surgery: a systematic
      review and meta-analysis.
AB  - CONTEXT: Recent advances in technology have led to the implementation of mini-
      and micro-percutaneous nephrolithotomy (PCNL) as well as retrograde intrarenal
      surgery (RIRS) in the management of kidney stones. OBJECTIVE: To provide a
      systematic review and meta-analysis of studies comparing RIRS with PCNL
      techniques for the treatment of kidney stones. EVIDENCE ACQUISITION: A systematic
      literature review was performed in March 2014 using the PubMed, Scopus, and Web
      of Science databases to identify relevant studies. Article selection proceeded
      according to the search strategy based on Preferred Reporting Items for
      Systematic Reviews and Meta-analysis criteria. A subgroup analysis was performed
      comparing standard PCNL and minimally invasive percutaneous procedures (MIPPs)
      including mini-PCNL and micro-PCNL with RIRS, separately. EVIDENCE SYNTHESIS: Two
      randomised and eight nonrandomised studies were analysed. PCNL techniques
      provided a significantly higher stone-free rate (weighted mean difference [WMD]:
      2.19; 95% confidence interval [CI], 1.53-3.13; p<0.00001) but also higher
      complication rates (odds ratio [OR]: 1.61; 95% CI, 1.11-2.35; p<0.01) and a
      larger postoperative decrease in haemoglobin levels (WMD: 0.87; 95% CI, 0.51
      1.22; p<0.00001). In contrast, RIRS led to a shorter hospital stay (WMD: 1.28;
      95% CI, 0.79-1.77; p<0.0001). At subgroup analysis, RIRS provided a significantly
      higher stone-free rate than MIPPs (WMD: 1.70; 95% CI, 1.07-2.70; p=0.03) but less
      than standard PCNL (OR: 4.32; 95% CI, 1.99-9.37; p=0.0002). Hospital stay was
      shorter for RIRS compared with both MIPPs (WMD: 1.11; 95% CI, 0.39-1.83; p=0.003)
      and standard PCNL (WMD: 1.84 d; 95% CI, 0.64-3.04; p=0.003). CONCLUSIONS: PCNL is
      associated with higher stone-free rates at the expense of higher complication
      rates, blood loss, and admission times. Standard PCNL offers stone-free rates
      superior to those of RIRS, whereas RIRS provides higher stone free rates than
      MIPPs. Given the added morbidity and lower efficacy of MIPPs, RIRS should be
      considered standard therapy for stones <2 cm until appropriate randomised studies
      are performed. When flexible instruments are not available, standard PCNL should
      be considered due to the lower efficacy of MIPPs. PATIENT SUMMARY: We searched
      the literature for studies comparing new minimally invasive techniques for the
      treatment of kidney stones. The analysis of 10 available studies shows that
      treatment can be tailored to the patient by balancing the advantages and
      disadvantages of each technique.

PMID- 25064688
TI  - Versican isoform V1 regulates proliferation and migration in high-grade gliomas.
AB  - Versican is a large chondroitin sulphate proteoglycan produced by several tumor
      cell types, including high-grade gliomas. Increased expression of distinct
      versican isoforms in the extracellular matrix plays a role in tumor cell growth,
      adhesion and migration. We have recently shown that transforming growth factor
      (TGF-beta)2, an important modulator of glioma invasion, interacts with versican
      isoforms V0/V1 during malignant progression of glioma in vitro. However, the
      distinct subtype of versican that modulates these effects could not be specified.
      Here, we show that transient down-regulation of V1 by siRNA leads to a
      significant reduction of proliferation and migration in glioblastoma cell lines
      and glioblastoma progenitor cells, whereas tumor cell attachment stays
      unaffected. We conclude that V1 plays a predominant role in modulating central
      pathophysiological mechanisms as proliferation and migration in glioblastoma.
      Considering that TGF-beta is a master regulator of glioma pathophysiology, and
      that V0/1 is induced by TGF-beta2, therapeutic regulation of V1 may induce
      meaningful effects on glioma cell migration not only in vitro, but also in vivo. 

PMID- 25064689
TI  - Heart rate, anxiety and performance of residents during a simulated critical
      clinical encounter: a pilot study.
AB  - BACKGROUND: High-fidelity patient simulation has been praised for its ability to
      recreate lifelike training conditions. The degree to which high fidelity
      simulation elicits acute emotional and physiologic stress among participants -
      and the influence of acute stress on clinical performance in the simulation
      setting - remain areas of active exploration. We examined the relationship
      between residents' self-reported anxiety and a proxy of physiologic stress (heart
      rate) as well as their clinical performance in a simulation exam using a
      validated assessment of non-technical skills, the Ottawa Crisis Resource
      Management Global Rating Scale (Ottawa GRS). METHODS: This was a prospective
      observational cohort study of emergency medicine residents at a single academic
      center. Participants managed a simulated clinical encounter. Anxiety was assessed
      using a pre- and post-simulation survey, and continuous cardiac monitoring was
      performed on each participant during the scenario. Performance in the simulation
      scenario was graded by faculty raters using a critical actions checklist and the
      Ottawa GRS instrument. RESULTS: Data collection occurred during the 2011 academic
      year. Of 40 eligible residents, 34 were included in the analysis. The median
      baseline heart rate for participants was 70 beats per minute (IQR: 62 - 78).
      During the simulation, the median maximum heart rate was 140 beats per minute
      (IQR: 137 - 151). The median minimum heart rate during simulation was 81 beats
      per minute (IQR: 72 - 92), and mean heart rate was 117 beats per minute (95% CI:
      111 - 123). Pre- and post-simulation anxiety scores were equal (mean 3.3, IQR: 3
      to 4). The minimum and maximum Overall Ottawa GRS scores were 2.33 and 6.67,
      respectively. The median Overall score was 5.63 (IQR: 5.0 to 6.0). Of the
      candidate predictors of Overall performance in a multivariate logistic regression
      model, only PGY status showed statistical significance (P = 0.02). CONCLUSIONS:
      Simulation is associated with physiologic stress, and heart rate elevation alone
      correlates poorly with both perceived stress and performance. Non-technical
      performance in the simulation setting may be more closely tied to one's level of
      clinical experience than to perceived or actual stress.

PMID- 25064690
TI  - Protein kinase C-beta: An emerging connection between nutrient excess and
      obesity.
AB  - There is currently a global epidemic of obesity as a result of recent changes in
      lifestyle. Excess body fat deposition is caused by an imbalance between energy
      intake and energy expenditure due to interactions between genetic and
      environmental factors. The signals and biological mechanisms that trigger fat
      accumulation by disrupting energy homeostasis are not well understood. There is
      considerable evidence now supporting a possible role of protein kinase C beta
      (PKCbeta) in energy homeostasis. This review highlights recent findings on the
      role of PKCbeta activation in the genesis and progression of obesity, and of
      PKCbeta repression in mediating the beneficial effects of physical exercise.
      Available data support a model in which adipose PKCbeta activation is among the
      initiating events that disrupt mitochondrial function through interaction with
      p66shc and amplify fat accumulation and adipose dysfunction, with systemic
      consequences. Manipulation of PKCbeta levels, activity, or signaling could
      provide a therapeutic approach to combat obesity and associated metabolic
      disorders.

PMID- 25064691
TI  - Disaster media coverage and psychological outcomes: descriptive findings in the
      extant research.
AB  - This review of the literature on disaster media coverage describes the events,
      samples, and forms of media coverage (television, newspapers, radio, internet)
      studied and examines the association between media consumption and psychological
      outcomes. A total of 36 studies representing both man-made and natural events met
      criteria for review in this analysis. Most studies examined disaster television
      viewing in the context of terrorism and explored a range of outcomes including
      posttraumatic stress disorder (PTSD) caseness and posttraumatic stress (PTS),
      depression, anxiety, stress reactions, and substance use. There is good evidence
      establishing a relationship between disaster television viewing and various
      psychological outcomes, especially PTSD caseness and PTS, but studies are too few
      to draw definitive conclusions about the other forms of media coverage that have
      been examined. As media technology continues to advance, future research is
      needed to investigate these additional media forms especially newer forms such as
      social media. 

PMID- 25064693
TI  - The use of anti-fibrinolytic agents in patients with HHT: a retrospective survey.
AB  - The anti-fibrinolytic agent tranexamic acid (TXA) has been used to reduce
      bleeding in patients with hereditary hemorrhagic telangiectasia (HHT); however,
      there are limited data on its efficacy and safety. We conducted a retrospective
      study at the HHT center, using a structured questionnaire and data abstraction to
      determine the safety and effectiveness of TXA. Forty-two patients from the HHT
      database with a definite clinical or genetic diagnosis of HHT with epistaxis
      and/or gastrointestinal bleeding and receiving TXA were included, and their
      Epistaxis Severity Score (ESS), blood transfusions, and hospitalizations prior to
      and during TXA use were assessed. Among the 42 patients, 29 responded to the
      questionnaire (78.3 %). The ESS declined from a mean of 6.9 +/- 2.7 to 4.3 +/-
      2.2 (p < 0.001), and there was a reduction in the percentage of patients
      receiving blood transfusion from 55.2 to 37.9 % (p = 0.095), hospitalizations
      from 58.6 to 37.9 % (p = 0.08), and medical care for epistaxis (i.e., clinic
      and/or emergency room visit) from 66.7 to 25.9 %. There was no difference in
      thrombosis (6.8 % before and during TXA use). TXA appears effective in the
      treatment of bleeding in patients with HHT, based on retrospective data.
      Prospective studies are warranted to confirm these preliminary results. 

PMID- 25064692
TI  - Effects of age on metacognitive efficiency.
AB  - Humans have a capacity to become aware of thoughts and behaviours known as
      metacognition. Metacognitive efficiency refers to the relationship between
      subjective reports and objective behaviour. Understanding how this efficiency
      changes as we age is important because poor metacognition can lead to negative
      consequences, such as believing one is a good driver despite a recent spate of
      accidents. We quantified metacognition in two cognitive domains, perception and
      memory, in healthy adults between 18 and 84years old, employing measures that
      dissociate objective task performance from metacognitive efficiency. We
      identified a marked decrease in perceptual metacognitive efficiency with age and
      a non-significant decrease in memory metacognitive efficiency. No significant
      relationship was identified between executive function and metacognition in
      either domain. Annual decline in metacognitive efficiency after controlling for
      executive function was ~0.6%. Decreases in metacognitive efficiency may explain
      why dissociations between behaviour and beliefs become more marked as we age. 

PMID- 25064694
TI  - Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen.
AB  - The effects of hypoxia on gene expression have been vigorously studied, but
      possible effects of small changes in oxygen tension have never been addressed.
      SUR2A is an atypical ABC protein serving as a regulatory subunit of sarcolemmal
      ATP-sensitive K(+) (KATP) channels. Up-regulation of SUR2A is associated with
      cardioprotection and improved physical endurance. Here, we have found that a 24h
      long exposure to slightly decreased ambient fractional concentration of oxygen
      (20% oxygen), which is an equivalent to oxygen tension at 350m above sea level,
      significantly increased levels of SUR2A in the heart despite that this drop of
      oxygen did not affect levels of O2, CO2 and hematocrit in the blood or myocardial
      levels of ATP, lactate and NAD/NADH/NAD(+). Hearts from mice exposed to 20%
      oxygen were significantly more resistant to ischaemia-reperfusion when compared
      to control ones. Decrease in fractional oxygen concentration of just 0.9% was
      associated with phosphorylation of ERK1/2, but not Akt, which was essential for
      up-regulation of SUR2A. These findings indicate that a small drop in oxygen
      tension up-regulates SUR2A in the heart by activating ERK signaling pathway. This
      is the first report to suggest that a minimal change in oxygen tension could have
      a profound signaling effect. 

PMID- 25064695
TI  - Effects of the axis of rotation and primordially solicited limb of high level
      athletes in a mental rotation task.
AB  - A recent set of studies has investigated the selective effects of particular
      physical activities that require full-body rotations, such as gymnastics and
      wrestling (Moreau, Clerc, Mansy-Dannay, & Guerrien, 2012; Steggemann, Engbert, &
      Weigelt, 2011), and demonstrated that practicing these activities imparts a clear
      advantage in in-plane body rotation performance. Other athletes, such as handball
      and soccer players, whose activities do require body rotations may have more
      experience with in-depth rotations. The present study examined the effect of two
      components that are differently solicited in sport practices on the mental
      rotation ability: the rotation axis (in-plane, in-depth) and the predominantly
      used limb (arms, legs). Handball players, soccer players, and gymnasts were asked
      to rotate handball and soccer strike images mentally, which were presented in
      different in-plane and in-depth orientations. The results revealed that handball
      and soccer players performed the in-depth rotations faster than in-plane
      rotations; however, the two rotation axes did not differ in gymnasts. In
      addition, soccer players performed the mental rotations of handball strike images
      slower. Our findings suggest that the development of mental rotation tasks that
      involve the major components of a physical activity allows and is necessary for
      specifying the links between this activity and the mental rotation performance.

PMID- 25064696
TI  - Spore dispersal of fetid Lysurus mokusin by feces of mycophagous insects.
AB  - The ecological roles and biological mechanisms of zoochory in plants have long
      been foci in studies of co-evolutionary processes between plants and animals.
      However, the dispersal of fungal spores by animals has received comparatively
      little attention. In this study, the dispersal of spores of a selected fetid
      fungus, Lysurus mokusin, via feces of mycophagous insects was explored by:
      collecting volatiles emitted by the fungus using dynamic headspace extraction and
      analyzing them by GC-MS; testing the capacity of mycophagous insects to disperse
      its spores by counting spores in their feces; comparing the germinability of L.
      mokusin spores extracted from feces of nocturnal earwigs and natural gleba of the
      fungus; and assessing the ability of L. mokusin volatiles to attract insects in
      bioassays with synthetic scent mixtures. Numerous spores were detected in
      insects' feces, the bioassays indicated that L. mokusin odor (similar to that of
      decaying substances) attracts diverse generalist mycophagous insects, and passage
      through the gut of Anisolabis maritima earwigs significantly enhanced the
      germination rate of L. mokusin spores. Therefore, nocturnal earwigs and diurnal
      flies probably play important roles in dispersal of L. mokusin spores, and
      dispersal via feces may be an important common dispersal mechanism for fungal
      reproductive tissue. 

PMID- 25064697
TI  - Gastrointestinal transfer: in vivo evaluation and implementation in in vitro and
      in silico predictive tools.
AB  - INTRODUCTION: The purpose of this study was to explore the transfer of drug
      solutions from stomach to small intestine and its impact on intraluminal drug
      concentrations in humans. The collected intraluminal data were used as reference
      to evaluate simulations of gastrointestinal transfer currently implemented in
      different in vitro and in silico absorption models. METHODS: Gastric and duodenal
      concentrations of the highly soluble and non-absorbable compound paromomycin were
      determined following oral administration to 5 healthy volunteers under the
      following conditions: fasted state, fed state and fed state in the presence of a
      transit-stimulating (domperidone) or transit-inhibiting (loperamide) agent. Based
      on the obtained intraluminal concentration-time profiles, gastrointestinal
      transfer (expressed as the half-life of gastric emptying) was analyzed using
      physiologically-based parameter estimation in Simcyp(r). Subsequently, the
      observed transfer profiles were used to judge the implementation of
      gastrointestinal transfer in 2 in vitro simulation tools (the TNO Intestinal
      Model TIM-1 and a three-compartmental in vitro model) and the Simcyp(r)
      population-based PBPK modeling platform. RESULTS: The observed duodenal
      concentration-time profile of paromomycin under fasting conditions, with a high
      average Cmax obtained after 15 min, clearly indicated a fast transfer of drug
      solutions from stomach to duodenum (estimated gastric half-life between 4 and 13
      min). The three-compartmental in vitro model adequately reflected the in vivo
      fasted state gastrointestinal transfer of paromomycin. For both TIM-1 and
      Simcyp(r), modifications in gastric emptying and dilutions were required to
      improve the simulation of the transfer of drug solutions. As expected, transfer
      from stomach to duodenum was delayed in the fed state, resulting in lower
      duodenal paromomycin concentrations and an estimated gastric half-life between 21
      and 40 min. Administration of domperidone or loperamide as transit-stimulating
      and transit-inhibiting agent, respectively, did not affect the fed state gastric
      half-life of emptying. CONCLUSION: For the first time, the impact of
      gastrointestinal transfer of solutions on intraluminal drug concentrations was
      directly assessed in humans. In vitro and in silico simulation tools have been
      validated and optimized using the in vivo data as reference.

PMID- 25064698
TI  - Yonkenafil: a novel phosphodiesterase type 5 inhibitor induces neuronal network
      potentiation by a cGMP-dependent Nogo-R axis in acute experimental stroke.
AB  - Yonkenafil is a novel phosphodiesterase type 5 (PDE5) inhibitor. Here we
      evaluated the effect of yonkenafil on ischemic injury and its possible mechanism
      of action. Male Sprague-Dawley rats underwent middle cerebral artery occlusion,
      followed by intraperitoneal or intravenous treatment with yonkenafil starting 2h
      later. Behavioral tests were carried out on day 1 or day 7 after reperfusion.
      Nissl staining, Fluoro-Jade B staining and electron microscopy studies were
      carried out 24h post-stroke, together with an analysis of infarct volume and
      severity of edema. Levels of cGMP-dependent Nogo-66 receptor (Nogo-R) pathway
      components, hsp70, apaf-1, caspase-3, caspase-9, synaptophysin, PSD-95/neuronal
      nitric oxide synthases (nNOS), brain-derived neurotrophic factor
      (BDNF)/tropomyosin-related kinase B (TrkB) and nerve growth factor
      (NGF)/tropomyosin-related kinase A (TrkA) were also measured after 24h.
      Yonkenafil markedly inhibited infarction and edema, even when administration was
      delayed until 4h after stroke onset. This protection was associated with an
      improvement in neurological function and was sustained for 7d. Yonkenafil
      enlarged the range of penumbra, reduced ischemic cell apoptosis and the loss of
      neurons, and modulated the expression of proteins in the Nogo-R pathway.
      Moreover, yonkenafil protected the structure of synapses and increased the
      expression of synaptophysin, BDNF/TrkB and NGF/TrkA. In conclusion, yonkenafil
      protects neuronal networks from injury after stroke. 

PMID- 25064700
TI  - Test-retest reliability of thermal quantitative sensory testing on two sites
      within the L5 dermatome of the lumbar spine and lower extremity.
AB  - INTRODUCTION: Quantitative sensory testing (QST) is widely used in human research
      to investigate the integrity of the sensory function in patients with pain of
      neuropathic origin, or other causes such as low back pain. Reliability of QST has
      been evaluated on both sides of the face, hands and feet as well as on the trunk
      (Th3-L3). In order to apply these tests on other body-parts such as the lower
      lumbar spine, it is important first to establish reliability on healthy
      individuals. The aim of this study was to investigate intra-rater reliability of
      thermal QST in healthy adults, on two sites within the L5 dermatome of the lumbar
      spine and lower extremity. METHODS: Test-retest reliability of thermal QST was
      determined at the L5-level of the lumbar spine and in the same dermatome on the
      lower extremity in 30 healthy persons under 40 years of age. Results were
      analyzed using descriptive statistics and intraclass correlation coefficient
      (ICC). Values were compared to normative data, using Z-transformation. RESULTS:
      Mean intraindividual differences were small for cold and warm detection
      thresholds but larger for pain thresholds. ICC values showed excellent
      reliability for warm detection and heat pain threshold, good-to-excellent
      reliability for cold pain threshold and fair-to-excellent reliability for cold
      detection threshold. ICC had large ranges of confidence interval (95%).
      CONCLUSION: In healthy adults, thermal QST on the lumbar spine and lower
      extremity demonstrated fair-to-excellent test-retest reliability.

PMID- 25064699
TI  - Benefit-risk assessment of orlistat in the treatment of obesity.
AB  - Orlistat, an inhibitor of intestinal lipase, has been available for the treatment
      of obesity for nearly two decades. In conjunction with a hypocaloric diet,
      orlistat treatment results in a placebo-subtracted reduction in body weight of
      around 3 kg at 1 year, and increases the likelihood of achieving clinically
      significant (>=5%) weight loss by around 20%. Orlistat-induced weight loss also
      confers modest improvements in systolic and diastolic blood pressure, low-density
      lipoprotein (LDL) cholesterol, glycemic parameters, and progression to diabetes
      in people with impaired glucose tolerance. Overall, it has a good safety profile,
      and serious adverse events (including reports of severe kidney and liver injury)
      are rare. However, a high rate of gastrointestinal side effects limits adherence
      to treatment.

PMID- 25064701
TI  - Hydrogen protects auditory hair cells from cisplatin-induced free radicals.
AB  - Cisplatin is a widely used chemotherapeutic agent for the treatment of various
      malignancies. However, its maximum dose is often limited by severe ototoxicity.
      Cisplatin ototoxicity may require the production of reactive oxygen species (ROS)
      in the inner ear by activating enzymes specific to the cochlea. Molecular
      hydrogen was recently established as an antioxidant that selectively reduces ROS,
      and has been reported to protect the central nervous system, liver, kidney and
      cochlea from oxidative stress. The purpose of this study was to evaluate the
      potential of molecular hydrogen to protect cochleae against cisplatin. We
      cultured mouse cochlear explants in medium containing various concentrations of
      cisplatin and examined the effects of hydrogen gas dissolved directly into the
      media. Following 48-h incubation, the presence of intact auditory hair cells was
      assayed by phalloidin staining. Cisplatin caused hair cell loss in a dose
      dependent manner, whereas the addition of hydrogen gas significantly increased
      the numbers of remaining auditory hair cells. Additionally, hydroxyphenyl
      fluorescein (HPF) staining of the spiral ganglion showed that formation of
      hydroxyl radicals was successfully reduced in hydrogen-treated cochleae. These
      data suggest that molecular hydrogen can protect auditory tissues against
      cisplatin toxicity, thus providing an additional strategy to protect against drug
      induced inner ear damage. 

PMID- 25064702
TI  - Prolyl oligopeptidase inhibition decreases extracellular acetylcholine levels in
      rat hippocampus and prefrontal cortex.
AB  - Several investigative prolyl oligopeptidase (PREP) inhibitors have been shown to
      improve learning and memory in various preclinical trials but the mechanism of
      action behind these effects remains unclear. Since hippocampal and cortical
      acetylcholine (ACh) is known to play an important role in cognitive processes,
      the effects of two potent PREP inhibitors, JTP-4819 and KYP-2047, on
      extracellular ACh levels in hippocampus and medial prefrontal cortex were
      assessed using in vivo microdialysis. Conscious rats were treated with a single
      dose (15 or 50MUmol/kg i.p.) of JTP-4819, KYP-2047 or vehicle, and extracellular
      ACh levels were monitored for 5h after treatment. In hippocampus, KYP-2047 had no
      significant effect on the ACh levels, although a trend towards decreased levels
      was observed at the higher dose. JTP-4819 had no significant effect on the
      hippocampal ACh levels at the lower dose (15MUmol/kg), but the higher dose
      (50MUmol/kg) significantly decreased ACh levels in hippocampus by about 25%. In
      cortex, the smaller dose (15MUmol/kg) of KYP-2047 decreased ACh levels maximally
      by 25%, and a similar (ns) effect was also observed after the higher dose. JTP
      4819 had no effect at the lower dose, but the higher dose decreased ACh levels
      maximally by about 30%. In conclusion, the present results suggest that the
      cognition-enhancing effects of investigative PREP inhibitors are not due to
      enhanced cholinergic transmission in hippocampus or cortex. 

PMID- 25064704
TI  - Diagnostic evaluation of hereditary hemochromatosis (HFE and non-HFE).
AB  - The management and understanding of hereditary hemochromatosis have evolved with
      recent advances in iron biology and the associated discovery of numerous genes
      involved in iron metabolism. HFE-related (type 1) hemochromatosis remains the
      most frequent form, characterized by C282Y mutation homozygosity. Rare forms of
      hereditary hemochromatosis include type 2 (A and B, juvenile hemochromatosis
      caused by HJV and HAMP mutation), type 3 (related to TFR2 mutation), and type 4
      (A and B, ferroportin disease). The diagnostic evaluation relies on comprehension
      of the involved pathophysiologic defect, and careful characterization of the
      phenotype, which gives clues to guide appropriate genetic testing. 

PMID- 25064703
TI  - Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells.
AB  - BACKGROUND: MicroRNA-34 is a family of three miRNAs that have been reported to
      function as tumor suppressor miRNAs and show decreased expression in various
      cancers. Here, we examine functions of miR-34c in basal-like breast cancer cells.
      METHODS: Data from The Cancer Genome Atlas (TCGA) were used for evaluation of
      expression in primary breast cancers. Cellular processes affected by miR-34c were
      investigated by thymidine incorporation, Annexin V-assays and cell cycle analysis
      using breast cancer cell lines. Effects on potential targets were analyzed with
      qPCR and Western blot. RESULTS: TCGA data revealed that miR-34c was expressed at
      lower levels in basal-like breast cancer tumors and low expression was associated
      with poor prognosis. Ectopic expression of miR-34c in basal-like breast cancer
      cell lines resulted in suppressed proliferation and increased cell death.
      Additionally, miR-34c influenced the cell cycle mainly by inducing an arrest in
      the G2/M phase. We found that expression levels of the known cell cycle
      regulating miR-34 targets CCND1, CDK4 and CDK6, were downregulated upon miR-34c
      expression in breast cancer cell lines. In addition, the levels of CDC23, an
      important mediator in mitotic progression, were suppressed following miR-34c
      expression, and siRNAs targeting CDC23 mimicked the effect of miR-34c on G2/M
      arrest. However, protein levels of PRKCA, a predicted miR-34c target and a known
      regulator of breast cancer cell proliferation were not influenced by miR-34c.
      CONCLUSIONS: Together, our results support the role of miR-34c as a tumor
      suppressor miRNA also in breast cancer.

PMID- 25064705
TI  - Iron-refractory iron deficiency anemia (IRIDA).
AB  - Iron deficiency anemia is a common global problem whose etiology is typically
      attributed to acquired inadequate dietary intake and/or chronic blood loss.
      However, in several kindreds multiple family members are affected with iron
      deficiency anemia that is unresponsive to oral iron supplementation and only
      partially responsive to parenteral iron therapy. The discovery that many of these
      cases harbor mutations in the TMPRSS6 gene led to the recognition that they
      represent a single clinical entity: iron-refractory iron deficiency anemia
      (IRIDA). This article reviews clinical features of IRIDA, recent genetic studies,
      and insights this disorder provides into the regulation of systemic iron
      homeostasis. 

PMID- 25064706
TI  - Sideroblastic anemia: diagnosis and management.
AB  - Sideroblastic anemias (SAs) may be acquired or congenital and share the features
      of disrupted utilization of iron in the erythroblast, ineffective erythropoiesis,
      and variable systemic iron overload. Congenital forms can have associated
      syndromic features or be nonsyndromic, and many of them have mutations in genes
      encoding proteins involved in heme biosynthesis, iron-sulfur cluster biogenesis,
      or mitochondrial protein synthesis. The mechanism(s) for the acquired clonal SA
      is undefined and is under intense study. Precise diagnosis of these disorders
      rests on careful clinical and laboratory evaluation, including molecular
      analysis. Supportive treatments usually provide for a favorable prognosis and
      often for normal survival. 

PMID- 25064707
TI  - Anemia of inflammation.
AB  - Anemia of inflammation (AI, also called anemia of chronic disease) is a common,
      typically normocytic, normochromic anemia that is caused by an underlying
      inflammatory disease. It is diagnosed when serum iron concentrations are low
      despite adequate iron stores, as evidenced by serum ferritin that is not low. In
      the setting of inflammation, it may be difficult to differentiate AI from iron
      deficiency anemia, and the 2 conditions may coexist. Treatment should focus on
      the underlying disease. Recent advances in molecular understanding of AI are
      stimulating the development of new pathophysiologically targeted experimental
      therapies. 

PMID- 25064708
TI  - The pathophysiology of transfusional iron overload.
AB  - The pathophysiologic consequences of transfusional iron overload (TIO) as well as
      the benefits of iron chelation therapy are best described in thalassemia major,
      although TIO is increasingly seen in other clinical settings. These consequences
      broadly reflect the levels and distribution of excess storage iron in the heart,
      endocrine tissues, and liver. TIO also increases the risk of infection, due to
      increased availability of labile iron to microorganisms. The authors suggest that
      extrahepatic iron distribution, and hence toxicity, is influenced by balance
      between generation of nontransferrin-bound iron from red cell catabolism and the
      utilization of transferrin iron by the erythron. 

PMID- 25064709
TI  - Transfusional iron overload and iron chelation therapy in thalassemia major and
      sickle cell disease.
AB  - Iron overload is an inevitable consequence of blood transfusions and is often
      accompanied by increased iron absorption from the gut. Chelation therapy is
      necessary to prevent the consequences of hemosiderosis. Three chelators,
      deferoxamine, deferiprone, and deferasirox, are presently available and a fourth
      is undergoing clinical trials. The efficacy of all 3 available chelators has been
      demonstrated. Also, many studies have shown the efficacy of the combination of
      deferoxamine plus deferiprone as an intensive treatment of severe iron overload.
      Alternating chelators can reduce adverse effects and improve compliance.
      Adherence to therapy is crucial for good results. 

PMID- 25064710
TI  - Diagnosis and management of iron deficiency anemia.
AB  - Iron deficiency anemia (IDA) is a common hematologic condition, affecting a
      substantial proportion of the world's women and young children. Optimal
      management of IDA requires an accurate diagnosis, identification and correction
      of the underlying cause, provision of medicinal iron therapy, and confirmation of
      treatment success. There are limited data to support current treatment approaches
      regarding oral iron preparation, dosing, monitoring, and duration of therapy. New
      intravenous iron agents have improved safety profiles, which may foster their
      increased utilization in the treatment of patients with IDA. Clinical trials
      focused on improving current treatment standards for IDA are sorely needed. 

PMID- 25064712
TI  - Iron disorders.

PMID- 25064711
TI  - Use of magnetic resonance imaging to monitor iron overload.
AB  - Treatment of iron overload requires robust estimates of total-body iron burden
      and its response to iron chelation therapy. Compliance with chelation therapy
      varies considerably among patients, and individual reporting is notoriously
      unreliable. Even with perfect compliance, intersubject variability in chelator
      effectiveness is extremely high, necessitating reliable iron estimates to guide
      dose titration. In addition, each chelator has a unique profile with respect to
      clearing iron stores from different organs. This article presents the tools
      available to clinicians to monitor their patients, focusing on noninvasive
      magnetic resonance imaging methods because they have become the de facto standard
      of care. 

PMID- 25064713
TI  - "You're losing your Ghanaianess": understanding malaria decision-making among
      Africans visiting friends and relatives in the UK.
AB  - BACKGROUND: In the UK, the majority of imported malaria infections occur in the
      London area among UK residents of African origin who travel to Africa visiting
      friends and relatives (VFRs). Effective malaria prevention measures are available
      but there is little understanding of the factors that enhance and constrain their
      use among VFRs. METHODS: Semi-structured interviews were undertaken with Africans
      resident in London who visited friends and relatives in Nigeria and Ghana (n =
      20) and with African VFRs recently treated for malaria (n = 6). Data collection
      took place between December 2007 and February 2011. Information on migration
      patterns and travel of respondents was collected and the data were analysed using
      a framework analysis approach. RESULTS: Knowledge of the link between mosquitoes
      and malaria was high. Factors influencing the use of mosquito avoidance methods
      included knowledge about the local environment, perceptions of the inevitability
      of contracting malaria, and a desire to fit with the norms of host families.
      Previous experience of bed nets, and the belief that more modern ways of
      preventing mosquito bites were available deterred people from using them.
      Chemoprophylaxis use was varied and influenced by: perceptions about continuing
      immunity to malaria; previous experiences of malaria illness; the cost of
      chemoprophylaxis; beliefs about the likely severity of malaria infections; the
      influence of friends in the UK; and, the way malaria is perceived and managed in
      Nigeria and Ghana. Malaria treatment was considered by many to be superior in
      Nigeria and Ghana than in the UK. A conceptual framework was developed to
      illustrate the manner in which these factors interact to affect malaria
      decisions. CONCLUSIONS: The use of malaria prevention among VFRs needs to be
      understood not only in terms of individual risk factors but also in relation to
      the context in which decisions are made. For VFRs, malaria decisions are
      undertaken across two distinct social and environmental contexts and within the
      structural constraints associated with each. Strategies for reducing the burden
      of malaria among VFRs that ignore this complexity are likely to face challenges.
      New approaches that take account of contextual as well as individual factors are
      required.

PMID- 25064714
TI  - The cross talk between microbiota and the immune system: metabolites take center
      stage.
AB  - The human meta-organism consists of more than 90% of microbial cells. The
      gastrointestinal tract harbors trillions of commensal microorganisms that
      influence the development and homeostasis of the host. Alterations in composition
      and function of the microbiota, termed dysbiosis, have been implicated in a
      multitude of metabolic and inflammatory diseases in humans. Thus, understanding
      the molecular underpinnings the cross talk between commensal bacteria and their
      host during homeostasis and dysbiosis may hold the key to understanding many
      idiopathic diseases. While most attention has focused on the innate recognition
      of immune-stimulatory bacterial molecules, such as cell wall components and
      nucleic acids, we emphasize here the impact of diet-dependent microbial
      metabolites on the development and function of the immune system. 

PMID- 25064715
TI  - Dust episodes in Beirut and their effect on the chemical composition of coarse
      and fine particulate matter.
AB  - Particles captured during dust episodes in Beirut originated from both the
      African and Arabian deserts. This particular air mixture showed an increase, over
      non-dust episodes, in particle volume distribution which was mostly noticed for
      particles ranging in sizes between 2.25 and 5 MUm. It also resulted in an
      increase in average mass concentration by 48.5% and 14.6%, for the coarse and
      fine fractions, respectively. Chemical analysis of major aerosol components
      accounted for 93% of fine PM and 71% of coarse PM. Crustal material (CM)
      dominated the coarse PM fraction, contributing to 39 +/- 15% of the total mass.
      Sea salt (SS) (11 +/- 10%) and secondary ions (SI) (11 +/- 7%) were the second
      most abundant elements. In the fine fraction, SI (36 +/- 14%) were the most
      abundant PM constituent, followed by organic matter (OM) (33 +/- 7%) and CM (13
      +/- 2%). Enrichment factors (EF) and correlation coefficients show that biogenic
      and anthropogenic sources contribute to the elemental composition of particles
      during dust episodes. This study emphasizes on the role played by the long-range
      transport of aerosols in changing the chemical composition of the organic and
      inorganic constituents of urban coarse and fine PM. The chemical reactions
      between aged urban and dust aerosols are enhanced during transport, leading to
      the formation of organo-nitrogenated and -sulfonated compounds. Their oligomeric
      morphologies are further confirmed by SEM-EDX measurements.

PMID- 25064716
TI  - PAH metabolites in European eels (Anguilla anguilla) as indicators of PAH
      exposure: different methodological approaches.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants of aquatic
      environments derived from pyrogenic and petrogenic sources. In fish, as in other
      vertebrates, PAHs are rapidly metabolized. However, the metabolites have been
      proven to induce multiple deleterious effects in fish. The concentrations of
      biliary polycyclic aromatic hydrocarbon metabolites in eels (Anguilla anguilla)
      caught in Polish waters were measured. The main objectives of the study were to
      provide information on the levels of PAH metabolites in eels inhabiting Polish
      waters and to discuss which methodological approach is appropriate for assessing
      PAH exposure in aquatic ecosystems. The non-normalized median concentration of 1
      OH Pyr and 1-OH Phe measured in eels from Polish waters ranged from 11 to 1642 ng
      ml(-1) bile and from 83 to 929 ng ml(-1) bile, respectively, depending on the
      sampling site. Data normalization in relation to bile pigment content reduced
      inter-site variation, and the normalized median concentrations of 1-OH Pyr and 1
      OH Phe ranged from 0.44 to 20.24 ng A(-1)380 and from 1.58 to 11.11 ng A(-1)380,
      respectively. Our study indicated that results were more consistent for the two
      species sampled in the same area (eel examined in the current study and flounder
      examined in our previous study) when the fluorescence response of diluted bile
      samples was compared than when concentrations of 1-OH Pyr determined with the
      mean of HPLC were compared.

PMID- 25064717
TI  - Wet deposition of particulate carbon to the Central North Atlantic Ocean.
AB  - Elemental carbon (EC) and water-insoluble organic carbon (WIOC) concentrations
      were measured in wet-only precipitation samples collected on Terceira Island
      (Azores, Portugal) between December 2009 and October 2010, to investigate
      temporal variations, source regions and wet deposition fluxes. The global volume
      weighted average (vwa) concentrations were 134 +/- 19 MUgC L(-1) for WIOC and
      15.0 +/- 1.6 MUgC L(-1) for EC, which fall within the range of values that have
      been found in the European background atmosphere. The WIOC concentration
      exhibited a temporal variation over the study period with a minimum in winter
      (vwa 88 +/- 16 MUgC L(-1)) and a maximum in summer (vwa 477 +/- 86 MUgC L(-1)).
      This trend was due to the higher dilution effect of winter rains and possibly to
      an increase of biogenic particulate carbon incorporation during the growing
      season. A different temporal variation was observed for the EC concentration with
      a minimum in summer (vwa 4.2 +/- 3.3 MUgC L(-1)) and a maximum in spring (vwa
      17.5 +/- 2.2 MUgC L(-1)). The observed trend was mainly related to changes in
      atmospheric circulation patterns over the Azores. A backward trajectory analysis
      was applied to identify possible source regions of particulate carbon. The
      highest WIOC and EC concentrations were associated with air masses that persisted
      for more than four days over the Central North Atlantic Ocean and with air masses
      arriving from Europe, respectively. Lower concentrations were observed in samples
      collected under the influence of back-trajectories from North America. Despite
      the lower abundance of particulate carbon, the wet deposition fluxes were higher
      for this group of samples, which reflects the higher amount of precipitation that
      is normally associated with air masses arriving in the Azores from the west and
      northwest sectors.

PMID- 25064718
TI  - Impact of bioethanol fuel implementation in transport based on modelled
      acetaldehyde concentration in the urban environment.
AB  - This study shows the results obtained from emission and air dispersion modelling
      of acetaldehyde in the city of Oslo and associated with the circulation of
      bioethanol vehicles. Two scenarios of bioethanol implementation, both realistic
      and hypothetical, have been considered under winter conditions; 1) realistic
      baseline scenario, which corresponds to the current situation in Oslo where one
      bus line is running with bioethanol (E95; 95% ethanol-5% petrol) among petrol and
      diesel vehicles; and 2) a hypothetical scenario characterized by a full
      implementation of high-blend bioethanol (i.e. E85) as fuel for transportation,
      and thus an entire bioethanol fleet. The results indicate that a full
      implementation of bioethanol will have a certain impact on urban air quality due
      to direct emissions of acetaldehyde. Acetaldehyde emissions are estimated to
      increase by 233% and concentration levels increase up to 650% with regard to the
      baseline. 

PMID- 25064719
TI  - Evaluation of five antibiotic resistance genes in wastewater treatment systems of
      swine farms by real-time PCR.
AB  - Antibiotics are widely used in livestock for infection treatment and growth
      promotion. Wastes from animal husbandry are a potential environmental source of
      antibiotic-insensitive pathogens, and the removal efficiency of the resistance
      genotypes in current wastewater treatment plants (WWTPs) is unknown. In this
      study, quantitative PCR was used for evaluating antibiotic resistance genes in
      wastewater treatment processes. Six wastewater treatment plants in different
      swine farms were included in this study, and five antibiotic resistance genes
      (ARGs) were tested for each treatment procedure. All of the tested ARGs including
      tetA, tetW, sulI, sulII, and blaTEM genes were detected in six swine farms with
      considerable amounts. The results showed that antibiotic resistance is prevalent
      in livestock farming. The ARG levels were varied by wastewater treatment
      procedure, frequently with the highest level at anaerobic treatment tank and
      lowest in the activated sludge unit and the effluents. After normalizing the ARG
      levels to 16S rRNA gene copies, the results showed that ARGs in WWTP units
      fluctuated partly with the quantity of bacteria. Regardless of its importance in
      biodegradation, the anaerobic procedure may facilitate bacterial growth thus
      increasing the sustainability of the antibiotic resistance genotypes. After
      comparing the copy numbers in influx and efflux samples, the mean removal
      efficiency of ARGs ranged between 33.30 and 97.56%. The results suggested that
      treatments in the WWTP could partially reduce the spread of antibiotic-resistant
      bacteria, and additional procedures such as sedimentation may not critically
      affect the removal efficiency. 

PMID- 25064720
TI  - Establishing a tracer-based sediment budget to preserve wetlands in Mediterranean
      mountain agroecosystems (NE Spain).
AB  - Mountain wetlands in Mediterranean regions are particularly threatened in
      agricultural environments due to anthropogenic activity. An integrated study of
      source-to-sink sediment fluxes was carried out in an agricultural catchment that
      holds a small permanent lake included in the European NATURA 2000 Network. More
      than 1000 yrs of human intervention and the variety of land uses pose a
      substantial challenge when attempting to estimate sediment fluxes which is the
      first requirement to protect fragile wetlands. To date, there have been few
      similar studies and those that have been carried out have not addressed such
      complex terrain. Geostatistical interpolation and GIS tools were used to derive
      the soil spatial redistribution from point (137)Cs inventories, and to establish
      the sediment budget in a catchment located in the Southern Pyrenees. The soil
      redistribution was intense and soil erosion predominated over soil deposition. On
      the areas that maintained natural vegetation the median soil erosion and
      deposition rates were moderate, ranging from 2.6 to 6 Mg ha yr(-1) and 1.5 to 2.1
      Mg ha yr(-1), respectively. However, in cultivated fields both erosion and
      deposition were significantly higher (ca. 20 Mg ha yr(-1)), and the maximum rates
      were always associated with tillage practices. Farming activities in the last
      part of the 20th century intensified soil erosion, as evidenced by the 1963
      (137)Cs peaks in the lake cores and estimates from the sediment budget indicated
      a net deposition of 671 Mg yr(-1). Results confirm a siltation risk for the lake
      and provide a foundation for designing management plans to preserve this
      threatened wetland. This comprehensive approach provides information useful for
      understanding processes that influence the patterns and rates of soil transfer
      and deposition within fragile Mediterranean mountain wetlands subjected to
      climate and anthropogenic stresses.

PMID- 25064721
TI  - Twice-daily brinzolamide/brimonidine fixed combination versus brinzolamide or
      brimonidine in open-angle glaucoma or ocular hypertension.
AB  - PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety
      of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) with that of
      brinzolamide 1% or brimonidine 0.2% monotherapy, all dosed 2 times per day (BID).
      DESIGN: Six-month, phase 3, randomized, multicenter, double-masked clinical
      trial. PARTICIPANTS: A total of 560 patients with primary open-angle glaucoma or
      ocular hypertension who had insufficient IOP reduction with their current
      therapeutic regimen or who were receiving >= 2 IOP-lowering medications.
      INTERVENTION: Patients received BBFC (n = 193), brinzolamide 1% (n = 192), or
      brimonidine 0.2% (n = 175) BID. MAIN OUTCOME MEASURES: The primary end point was
      mean change in diurnal IOP from baseline to month 3. Supportive end points
      included mean diurnal IOP change from baseline at week 2, week 6, and month 6;
      and mean IOP, mean IOP change from baseline, mean percentage IOP change from
      baseline, and percentage of patients with IOP <18 mmHg at week 2, week 6, month
      3, and month 6 at each assessment time point (i.e., 9 am, 11 am, and 4 pm).
      Adverse events were recorded throughout the study. RESULTS: Baseline diurnal IOP
      was similar among groups (mean +/- standard deviation: BBFC, 25.9 +/- 0.19 mmHg;
      brinzolamide, 25.9 +/- 0.20 mmHg; brimonidine, 26.0 +/- 0.19 mmHg). At month 3,
      BBFC lowered mean diurnal IOP from baseline to a significantly greater extent
      than brinzolamide (least squares [LS] mean difference: -1.4 mmHg; P < 0.0001; t
      test) and brimonidine (LS mean difference: -1.5 mmHg; P < 0.0001). All supportive
      end points corroborated the results of the primary efficacy analysis. Mean
      percentage reductions in IOP from baseline were 26.7% to 36.0% with BBFC, 22.4%
      to 27.9% with brinzolamide, and 20.6% to 31.3% with brimonidine. The most common
      adverse drug reactions were ocular side effects, including hyperemia, blurred
      vision, allergic-type reactions, and discomfort. The incidence of hyperemia of
      the eye was slightly lower with brinzolamide than with BBFC and brimonidine,
      whereas blurred vision and ocular discomfort were slightly more common with BBFC
      than with brinzolamide or brimonidine. CONCLUSIONS: Brinzolamide 1% and
      brimonidine 0.2% fixed combination administered BID had a significantly greater
      IOP-lowering effect than either brinzolamide or brimonidine alone and displayed a
      safety profile consistent with its individual components.

PMID- 25064722
TI  - Re: Levy-Clarke et al.: Expert panel recommendations for the use of anti-tumor
      necrosis factor biologic agents in patients with ocular inflammatory disorders
      (Ophthalmology 2014;121:785-96).

PMID- 25064723
TI  - Outer retinal tubulation in the comparison of age-related macular degeneration
      treatments trials (CATT).
AB  - PURPOSE: To determine the prevalence of, risk factors for, and visual acuity (VA)
      correlations with outer retinal tubulation (ORT) seen on spectral-domain optical
      coherence tomography (SD OCT) in eyes with neovascular age-related macular
      degeneration (AMD) after anti-vascular endothelial growth factor (VEGF) therapy.
      DESIGN: Prospective cohort study within a randomized clinical trial.
      PARTICIPANTS: Patients with SD OCT images at weeks 56 and 104 in the Comparison
      of AMD Treatments Trials (CATT). METHODS: Participants in the CATT were assigned
      randomly to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a
      monthly or pro re nata (PRN) injection-dosing regimen. A subset of eyes was
      imaged with SD OCT beginning at week 56. Cirrus 512*128 or Spectralis 20 degrees
      *20 degrees  volume cube scan protocols were used to acquire SD OCT images. Two
      independent readers at the CATT OCT reading center graded scans, and a senior
      reader arbitrated discrepant grades. The prevalence of ORT, identified as tubular
      structures seen on at least 3 consecutive Cirrus B scans or 2 consecutive
      Spectralis B scans, was determined. The associations of patient-specific and
      ocular features at baseline and follow-up with ORT were evaluated by univariate
      and multivariate analyses. MAIN OUTCOME MEASURES: Outer retinal tubulations.
      RESULTS: Seven of 69 eyes (10.1%) at 56 weeks and 64 of 368 eyes (17.4%) at week
      104 had ORTs. Absence of diabetes, poor VA, blocked fluorescence, geographic
      atrophy, greater lesion size, and presence of subretinal hyperreflective material
      at baseline were associated independently with greater risk of ORT at 104 weeks
      (P < 0.05). Neither drug nor dosing regimen were associated significantly with
      ORT. The mean VA of eyes with ORT at week 104 (58.5 Early Treatment Diabetic
      Retinopathy Study letters) was worse than the mean VA of eyes without ORT (68.8
      letters; P < 0.0001). CONCLUSION: At 2 years after initiation of anti-VEGF
      therapy for neovascular AMD, ORTs are present in a substantial proportion of
      eyes. We identified baseline features that independently predict ORTs. It is
      important to identify ORTs because eyes with ORTs have worse VA outcomes than
      those without this finding.

PMID- 25064724
TI  - Epidemiology of epiretinal membrane in a large cohort of patients with uveitis.
AB  - OBJECTIVE: To identify clinical characteristics associated with the presence of
      epiretinal membrane (ERM) in patients with uveitis. DESIGN: Case-control study.
      PARTICIPANTS AND CONTROLS: Five hundred ninety-eight subjects seen in a single
      tertiary referral clinic between January 1, 2008, and December 31, 2011, who were
      diagnosed with uveitis. METHODS: Spectral-domain optical coherence tomography (SD
      OCT) images of all subjects were reviewed to assess for ERM. A multivariate
      logistic regression analysis was performed to compare characteristics of subjects
      with ERM (cases) with characteristics of subjects without ERM (controls). A
      second multivariate analysis assessed the relationship between ERM and visual
      acuity. Fundus photographs were reviewed to compare SD OCT ascertainment of ERM
      with photographic ascertainment. MAIN OUTCOME MEASURES: Presence or absence of
      ERM on OCT imaging. RESULTS: Of 598 uveitic participants, 246 (41%) were found to
      have ERM in at least 1 eye on SD OCT imaging. The prevalence of ERM by
      Standardization of Uveitis Nomenclature anatomic subtype was 28.1% for anterior
      uveitis, 57.0% for intermediate uveitis, and 43.4% for posterior uveitis and
      panuveitis. Multivariate analysis showed that the following clinical factors were
      associated significantly with ERM: older age (3% increased risk per year of age;
      95% confidence interval [CI], 1.02-1.05), intermediate uveitis (odds ratio [OR],
      3.41; 95% CI, 1.67-6.96), posterior uveitis and panuveitis (OR, 1.81; 95% CI,
      1.09-3.01), male sex (OR, 1.59; 95% CI, 1.05-2.42), and history of cataract
      surgery (OR, 1.78; 95% CI, 1.13-2.79). When adjusted for covariates, eyes with
      ERM had a mean logarithm of the minimum angle of resolution visual acuity of 0.58
      (20/76) versus 0.48 (20/60) in non-ERM eyes (P = 0.039). Of OCT-defined ERMs in
      this cohort, 38% were not detectable on fundus photographs. CONCLUSIONS:
      Epiretinal membrane is a common complication of uveitis that is associated with
      patient age, intermediate uveitis, posterior uveitis, panuveitis, male sex, and
      previous cataract surgery. It can contribute independently to vision loss in
      uveitic eyes. In uveitis, OCT is more sensitive than fundus photography for
      identification of ERM.

PMID- 25064725
TI  - [Active management of the second twin for vaginal delivery: ruptured versus
      intact membranes. Apropos a series of 182 patients].
AB  - AIM: The vaginal management of the second twin (T2) differs throughout our
      country. In 2009, the French National College of Gynecologists and Obstetricians
      released practice guidelines, with low-level evidence, encouraging active
      management of the second twin, using maneuvers with intact membrane. PATIENTS AND
      METHODS: In our level III labour ward, these maneuvers are systematically
      performed when the second twin is in a breech or transverse presentation and
      after ruptured membranes in most cases. We studied 182 twin pregnancies with
      active management of the T2 at more than 28 weeks of gestation, from 1st January
      1996 to 31st December 2010, by comparing the membrane status during delivery of
      T2. RESULTS: The results did not show any significant differences between the two
      groups of patients concerning the neonatal or maternal results. The technique is
      feasible, even by residents. Our results show that total breech extraction of the
      second twin with ruptured membranes is feasible, which allows for reappraisal of
      the national recommendations. CONCLUSION: In our practice, it is possible to
      actively deliver the T2 with ruptured membranes without altering maternal and
      fetal prognosis and thus simplifying learning for young doctors.

PMID- 25064726
TI  - Influence of the physiological variability of fasted gastric pH and tablet
      retention time on the variability of in vitro dissolution and simulated plasma
      profiles.
AB  - The aim of the present study was to show that the physiological variability of
      fasted gastric pH and tablet gastric retention time contributes to the overall
      variability of simulated plasma profiles of diclofenac. Those two parameters were
      implemented into dissolution study and plasma profiles were simulated under
      assumptions that in vitro dissolution well represents that occurring in vivo, and
      that absorption profiles are identical to dissolution profiles, as diclofenac is
      a highly permeable drug. Dissolution experiments were performed using USP 2
      apparatus and two consecutive dissolution media, namely, an acidic medium of
      various pH (ranging from 1-3), where tablets were kept for a certain time (10-200
      min), and phosphate buffer (pH 6.8). It was shown that the acid pH value and acid
      retention time of tablets affect in vitro drug release, and consequently also
      influence the simulated plasma profiles. Lower acid pH resulted in lower plasma
      peaks at each studied acid retention time. Longer acid retention time caused
      lower plasma concentrations at lower acid pH values, whereas at pH 3 higher
      plasma concentrations were noted. Additionally, it was demonstrated that the
      variability of both parameters represents an important contribution to the
      overall variability of plasma profiles.

PMID- 25064727
TI  - Activation energies of diffusion of organic migrants in cyclo olefin polymer.
AB  - Cyclo olefin polymer (COP) is an amorphous polymer with good optical transparency
      and barrier properties, which is increasingly used for pharmaceutical packaging
      applications like pre-filled syringes, plastic vials, nutrition bags and blisters
      as well as for micro-well plates. For regulatory purposes, it is important to
      know the amount and quantity of compounds which migrate from the polymer into the
      pharmaceutical product. Within the study, diffusion coefficients of organic
      (model) compounds in COP at various temperatures were determined and the
      activation energies of diffusion were calculated according to the Arrhenius
      approach. Correlations were established between the molecular volume V of the
      migrating compound and the activation energy of diffusion EA as well as between
      the pre-exponential factor in the Arrhenius equation D0 and EA. From these
      correlations a prediction model was established for the migration of organic
      compounds in COP. This might be a useful tool supporting the evaluation process
      of COP packed pharmaceutical products. 

PMID- 25064728
TI  - Influence of pH and method of crystallization on the solid physical form of
      indomethacin.
AB  - The purpose of this study was to investigate the effect of pH and method of
      crystallization on the solid physical form of indomethacin (IDM). IDM, a non
      steroidal anti-inflammatory drug poorly soluble in water, underwent two different
      crystallization methods: crystallization by solvent evaporation under reduced
      pressure at 50.0 degrees C (method A), and crystallization by cooling of solution
      from 50.0 to 5.0 degrees C (method B). In both cases, several aqueous ethanolic
      solutions of IDM of different pHs were prepared. pHs were adjusted by adding
      acidic solutions (HCl 2M) or alkali (NaOH or NH4OH 2M) to an aqueous ethanolic
      solution of IDM. Thus, several batches were recovered after crystallization. The
      chemical stability of IDM was verified through (1)H NMR and mass spectroscopy
      (FIA-ESI-MS), that revealed that IDM degraded in strong alkali media (pH >= 12).
      Crystals obtained under different crystallization conditions at pHs of 1.0, 4.5,
      7.0, 8.0, 10.0 and chemically stable were thus characterized for crystal habit by
      scanning electron microscopy, for thermal behaviour by differential scanning
      calorimetry, and thermogravimetry, and for solid state by X-ray powder
      diffractometry. Under the Method A, IDM always crystallized into pure metastable
      alpha form when solutions were acidified or alkalized respectively with HCl and
      NH4OH. On the contrary, in presence of NaOH, IDM crystallized under a mixture of
      alpha and sodium trihydrate form, because the presence of the sodium counter ion
      orientates the crystallization towards the formation of the trihydrate salt.
      Under the method B, at pH of 1.0, IDM crystallized under the alpha form; at pH
      4.5, IDM crystallized under the form alpha in presence of some nuclei of gamma
      form; at pH 7.0, 8.0, and 10.0 for NH4OH, IDM crystallized under the most stable
      polymorph gamma form, whereas in presence of NaOH, a mix of alpha, and salt forms
      was formed whatever the pH of the solution.

PMID- 25064729
TI  - Cancer stem cell detection and isolation.
AB  - Only 10 % of cancer-related deaths result from primary tumors; most are caused by
      metastatic tumors. It is believed that the metastatic power of tumor cells is
      attributed to features of a stem cell-like subpopulation of tumor cells known as
      cancer stem cells (CSCs). Cancer stem cells are resistant to chemotherapeutic
      treatments and can induce dormancy in tumor cells for long periods. Detection,
      isolation, and characterization of CSCs in solid tumors are hallmarks of cancer
      targeted therapies in recent years. There are inevitable similarities between
      normal and cancer stem cells; therefore, finding specific methods or markers to
      differentiate them is critical to cancer therapies. Considering CSCs involvement
      in tumor relapse and chemotherapeutic resistance, identification of such cells in
      tumors is imperative for effective targeted therapy. The present review
      introduces practical and specific protocols used to isolate CSCs from solid
      tumors from colon, esophagus, liver, breast, brain, and cervix.

PMID- 25064730
TI  - Expression patterns of three regulation enzymes in glycolysis in esophageal
      squamous cell carcinoma: association with survival.
AB  - Enhanced glycolysis is a common trait of many types of human cancers. This study
      was to detect the expression pattern of three regulatory enzymes during
      glycolysis in esophageal squamous cell carcinoma (ESCC) and to investigate their
      correlation with patients' outcome based on banked pathology material. A total of
      141 surgically resected specimens of primary ESCC patients without prior
      treatments were retrospectively recruited from the First Affiliated Hospital of
      Wenzhou Medical College Hospital from 2007 to 2009. Expression of HK1, PFKB, and
      PKM2 in ESCC specimens was analyzed by immunohistochemical staining and Western
      blotting analysis. HK1-shRNA was used to knock down HK1 expression in ESCC cells,
      and the functional significance was assessed by CCK8 assay. It was found that the
      expression of two glycolytic enzymes, HK1 and PKM2, was associated with disease
      progression, invasion, and poor survival of patients with ESCC. Silence of HK1
      inhibited cell proliferation in vitro and suppressed phospho-S6 kinase
      expression. Our findings suggest that activation of key enzymes in glycolysis
      might serve as potential therapeutic targets and/or prognostic factors for
      patients with ESCC.

PMID- 25064731
TI  - The clinical value of serum hepatocyte growth factor levels in patients
      undergoing primary radiotherapy for glioma: effect on progression-free survival.
AB  - Hepatocyte growth factor (HGF) has been shown to be overexpressed in gliomas, and
      high-grade gliomas (glioblastoma multiforme) express more HGF than lower-grade
      astrocytoma, and HGF enhances their resistance to radiotherapy. To examine the
      effect of serum HGF levels on the likelihood of response to radiotherapy and the
      disease-free survival in patients with glioma, the blood samples of the patients
      were collected before commencing treatment and serum HGF was measured by
      quantitative ELISA in 48 patients with glioma grade I-IV, and all patients
      underwent primary conventionally fractionated radiotherapy. For statistical
      analysis, SPSS Version 13.0 software was used. Thirty-eight of the 48 patients
      had a response to treatment, and ten patients had persistent disease at 3 months.
      Overall, the median serum HGF level was 1,219.5 pg/ml (range 650.4-2,264.7
      pg/ml). Eight patients with local failure had HGF levels >1,219.5 pg/ml, and 28
      patients with response had serum HGF level of <= 1,219.5 pg/ml (P = 0.01). The
      median time to progression was 6 months in patients with HGF level of >1,219.5
      pg/ml compared with 17 months in patients with HGF level of <= 1,219.5 pg/ml (log
      rank, P = 0.041). In multivariate analysis, serum HGF, the KPS, tumour size and
      pathological grade, but not the patient's age, gender and oligodendroglial
      component influenced the progression-free survival. Elevated pre-therapeutic
      serum HGF levels are associated with poor response and a shorter time to
      progression in patients with glioma undergoing primary radiotherapy.

PMID- 25064732
TI  - Prognostic potential of microRNA-138 and its target mRNA PDK1 in sera for
      patients with non-small cell lung cancer.
AB  - microRNA (miR)-138 has been recognized as a potential tumor suppressor via
      regulating 3-phosphoinositide-dependent protein kinase-1 (PDK1) expression in non
      small cell lung cancer (NSCLC) cells. The aim of this study was to investigate
      miR-138 and PDK1 mRNA expression in serum of NSCLC and their associations with
      patients' prognosis. miR-138 and PDK1 mRNA expressions in 100 NSCLCs and 100
      healthy control sera were detected by quantitative real-time PCR. miR-138
      expression level was significantly lower in NSCLC serum samples than in healthy
      control serum samples (P < 0.001), while PDK1 mRNA expression level was
      significantly increased in NSCLC serum samples compared to healthy control serum
      samples (P < 0.001). In addition, miR-138 downregulation and PDK1 upregulation
      were both significantly associated with advanced tumor-node-metastasis (TNM)
      stage (both P = 0.002) and positive lymph node metastasis (both P = 0.01) of
      NSCLC patients. Moreover, the overall survival of NSCLC patients with low miR-138
      expression or high PDK1 mRNA expression was obviously shorter than those with
      high miR-138 expression or low PDK1 mRNA expression (both P < 0.001). Notably,
      NSCLC patients with combined miR-138 downregulation and PDK1 upregulation (miR
      138-low/PDK1-high) had shortest overall survival (P < 0.001). Furthermore,
      multivariate analysis showed that miR-138 expression (P = 0.01), PDK1 expression
      (P = 0.01), and combined expression of miR-138 and PDK1 (miR-138/PDK1, P = 0.001)
      were all independent prognostic factors for overall survival in NSCLC patients.
      Deregulation of miR-138/PDK1 cascade may be implicated in carcinogenesis and
      cancer progression of human NSCLC. More importantly, miR-138 and PDK1 may
      synergistically predict patients' prognosis and their combination may represent a
      promising prognostic biomarker of human NSCLC.

PMID- 25064733
TI  - Evaluation of soluble CD44 protein marker to distinguish the premalignant and
      malignant carcinoma cases in cervical cancer patients.
AB  - The main objective of the present study was to estimate the levels of soluble
      CD44 in cervical cancer patients by determining whether it consistently
      discriminates the carcinoma of the cervix from early or premalignant stage of the
      cervical cancer. Serum concentrations of sCD44s in cervical cancer patients were
      determined by an enzyme-linked immunosorbent assay from serum of 50 cases of
      cervical cancer patients and 50 cases of suspected patients with premalignant
      disease of cervical intraepithelial neoplasia. The sensitivity and specificity of
      the test for differentiating carcinoma of the cervix from premalignant stage were
      evaluated by plotting receiver operating characteristic (ROC) curve. Significant
      increase in the levels of soluble CD44 was observed in cervical cancer patients
      (664.80 +/- 26.58 ng/ml), when compared to healthy (P < 0.001) and suspected (P <
      0.05) or premalignant cases (275.19 +/- 24.39 and 514.33 +/- 54.57 ng/ml,
      respectively). High-grade squamous intraepithelial lesions, adenocarcinoma in
      situ and premalignance with dysplasia show significant (P < 0.001) increase in
      the concentration of soluble CD44 levels when compared to other types. A ROC
      curve was plotted and estimated the threshold value as 633.11 ng/ml. In
      conclusion, the data indicated an up-regulation of soluble CD44 protein which
      detect and differentiates the cervical carcinoma from premalignant cases with
      62.6 % sensitivity.

PMID- 25064734
TI  - A B101-O16 hybrid sequence is responsible for a Bweak phenotype in the ABO blood
      group.

PMID- 25064735
TI  - Stature estimation in Japanese cadavers based on scapular measurements using
      multidetector computed tomography.
AB  - This study assessed the correlation between stature and scapular measurements in
      a Japanese population, using three-dimensional (3D) computed tomographic (CT)
      images, and derived regression equations for predicting stature. A total of 194
      cadavers (100 males 94 females) underwent postmortem CT (PMCT) and subsequent
      forensic autopsy in our department between May 2011 and April 2014. Left and
      right longitudinal scapular lengths (LLSL and RLSL, respectively) and left and
      right transverse scapular lengths (LTSL and RTSL, respectively) were measured on
      3D CT reconstructed images that extracted only scapular data. The correlation
      between stature and each of the scapular measurements were analyzed using Pearson
      product-moment correlation coefficients. The four variables correlated
      significantly with stature, regardless of sex. The LLSL measurement had the
      lowest standard error of estimation value among all subjects (4.22 cm) and among
      all females (4.37 cm), whereas the RLSL measurement had the lowest standard error
      of estimation value among all males (3.75 cm). The results of this study indicate
      that scapular measurements may be useful for the forensic estimation of the
      stature of Japanese individuals, particularly in cases where better predictors,
      such as long bone lengths, are unavailable.

PMID- 25064736
TI  - The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA
      damage.
AB  - Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but
      the mechanisms involved remained elusive. Here we discover an in trans signalling
      mechanism that triggers pan-nuclear silencing of rRNA transcription in response
      to DNA damage. This is associated with transient recruitment of the Nijmegen
      breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses,
      into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar
      factor implicated in ribosome biogenesis and mutated in Treacher Collins
      syndrome, as an interaction partner of NBS1, and demonstrate that NBS1
      translocation and accumulation in the nucleoli is Treacle dependent. Finally, we
      provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli
      regulates rRNA silencing in trans in the presence of distant chromosome breaks. 

PMID- 25064737
TI  - DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti
      tubulin drug-induced apoptosis.
AB  - Microtubule-targeting chemotherapeutics induce apoptosis in cancer cells by
      promoting the phosphorylation and degradation of the anti-apoptotic BCL-2 family
      member MCL1. The signalling cascade linking microtubule disruption to MCL1
      degradation remains however to be defined. Here, we establish an in vivo
      screening strategy in Caenorhabditis elegans to uncover genes involved in
      chemotherapy-induced apoptosis. Using an RNAi-based screen, we identify three
      genes required for vincristine-induced apoptosis. We show that the DEP domain
      protein LET-99 acts upstream of the heterotrimeric G protein alpha subunit GPA-11
      to control activation of the stress kinase JNK-1. The human homologue of LET-99,
      DEPDC1, similarly regulates vincristine-induced cell death by promoting JNK
      dependent degradation of the BCL-2 family protein MCL1. Collectively, these data
      uncover an evolutionarily conserved mediator of anti-tubulin drug-induced
      apoptosis and suggest that DEPDC1 levels could be an additional determinant for
      therapy response upstream of MCL1. 

PMID- 25064738
TI  - Serotonin and sudden death: differential effects of serotonergic drugs on seizure
      induced respiratory arrest in DBA/1 mice.
AB  - In the DBA/1 mouse model of sudden unexpected death in epilepsy (SUDEP),
      administration of a selective serotonin (5-HT) reuptake inhibitor (SSRI),
      fluvoxamine, completely suppressed seizure-induced respiratory arrest (S-IRA) at
      30 min after administration (i.p.) in a dose-related manner without blocking
      audiogenic seizures (AGSz), but another SSRI, paroxetine, reduced S-IRA but with
      a delayed (24 h) onset and significant toxicity. A serotonin-norepinephrine
      reuptake inhibitor, venlafaxine, reduced S-IRA incidence, but higher doses were
      ineffective. A selective 5-HT7 agonist, AS-19, was totally ineffective in
      reducing S-IRA. In developing DBA/1 mice that had not previously experienced
      AGSz, administration of a nonselective 5-HT antagonist, cyproheptadine, induced a
      significantly greater incidence of S-IRA than that of saline. This study confirms
      that certain drugs that enhance the activation of 5-HT receptors are able to
      prevent S-IRA, but not all serotonergic drugs are equally effective, which may be
      relevant to the potential use of these drugs for SUDEP prevention. Serotonergic
      antagonists may be problematic in patients with epilepsy.

PMID- 25064739
TI  - Validation of the Patient Health Questionnaire-9 (PHQ-9) for depression screening
      in adults with epilepsy.
AB  - OBJECTIVE: This study aimed to assess the accuracy and operating characteristics
      of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults
      with epilepsy. METHODS: Tertiary epilepsy center patients served as the study
      population, with 237 agreeing to structured interview using the Mini
      International Neuropsychiatric Interview (MINI), a "gold standard" instrument
      developed for rapid diagnosis of neuropsychiatric disorders, including major
      depressive disorder (MDD); 172 also completed the PHQ-9, and 127 completed both
      the PHQ-9 and the Neurological Disorders Depression Inventory for Epilepsy (NDDI
      E) within two days of the MINI. Sensitivity, specificity, positive and negative
      predictive values, and areas under the ROC curves for each instrument were
      determined. Cut-points of 10 for the PHQ-9 and 15 for the NDDI-E were used, and
      ratings at or above the cut-points were considered screen-positive. The PHQ-9 was
      divided into cognitive/affective (PHQ-9/CA) and somatic (PHQ-9/S) subscales to
      determine comparative depression screening accuracy. RESULTS: The calculated
      areas under the ROC curves for the PHQ-9 (n=172) and the PHQ-9/CA and PHQ-9/S
      subscales were 0.914, 0.924, and 0.846, respectively, with the PHQ-9 more
      accurate than the PHQ-9/S (p=0.002) but not different from the PHQ-9/CA
      (p=0.378). At cut-points of 10 and 15, respectively, the PHQ-9 had higher
      sensitivity (0.92 vs 0.87) but lower specificity (0.74 vs 0.89) compared with the
      NDDI-E. The areas under the ROC curves of the PHQ-9 and the NDDI-E showed similar
      accuracy (n=127; 0.930 vs 0.934; p=0.864). SIGNIFICANCE: The PHQ-9 is an
      efficient and nonproprietary depression screening instrument with excellent
      accuracy validated for use in adult patients with epilepsy as well as multiple
      other medical populations.

PMID- 25064740
TI  - The relationship between thought suppression and retrieval-induced forgetting: an
      analysis of witness memories.
AB  - The aim of the present research was to examine the relationship between
      individual differences in thought suppression and retrieval-induced forgetting
      (RIF) in witness-like situations. We predicted that people who are more prone to
      suppress undesired thoughts and memories would demonstrate a stronger RIF effect.
      Consistent with findings obtained in a US sample (Blumberg in Personal Individ
      Differ 29:943-950, 2000), results of a preliminary study (Study 1) confirmed the
      three-factor structure of the white bear suppression inventory (WBSI): the
      tendency to rely on thought suppression (suppression dimension), the frequency of
      experiencing intrusive thoughts (intrusion dimension), and the frequency of using
      self-distraction to avoid undesired thoughts (self-distraction dimension).
      Consistent with our hypotheses, Study 2 found that only the suppression sub
      dimension of the WBSI was positively and significantly related to RIF.
      Theoretical expectations of these findings and implications for witness research
      are discussed. 

PMID- 25064741
TI  - Statewide regionalization of postarrest care for out-of-hospital cardiac arrest:
      association with survival and neurologic outcome.
AB  - STUDY OBJECTIVE: For out-of-hospital cardiac arrest, authoritative, evidence
      based recommendations have been made for regionalization of postarrest care.
      However, system-wide implementation of these guidelines has not been evaluated.
      Our hypothesis is that statewide regionalization of postarrest interventions,
      combined with emergency medical services (EMS) triage bypass, is associated with
      improved survival and neurologic outcome. METHODS: This was a prospective before
      after observational study comparing patients admitted to cardiac receiving
      centers before implementation of the interventions ("before") versus those
      admitted after ("after"). In December 2007, the Arizona Department of Health
      Services began officially recognizing cardiac receiving centers according to
      commitment to provide specified postarrest care. Subsequently, the State EMS
      Council approved protocols allowing preferential EMS transport to these centers.
      Participants were adults (>= 18 years) experiencing out-of-hospital cardiac
      arrest of presumed cardiac cause who were transported to a cardiac receiving
      center. Interventions included (1) implementation of postarrest care at cardiac
      receiving centers focusing on provision of therapeutic hypothermia and coronary
      angiography or percutaneous coronary interventions (catheterization/PCI); and (2)
      implementation of EMS bypass triage protocols. Main outcomes included discharged
      alive from the hospital and cerebral performance category score at discharge.
      RESULTS: During the study (December 1, 2007, to December 31, 2010), 31 hospitals
      were recognized as cardiac receiving centers statewide. Four hundred forty
      patients were transported to cardiac receiving centers before and 1,737 after.
      Provision of therapeutic hypothermia among patients with return of spontaneous
      circulation increased from 0% (before: 0/145; 95% confidence interval [CI] 0% to
      2.5%) to 44.0% (after: 300/682; 95% CI 40.2, 47.8). The post return of
      spontaneous circulation catheterization PCI rate increased from 11.7% (17/145;
      95% CI 7.0, 18.1) before to 30.7% (210/684; 95% CI 27.3, 34.3) after. All-rhythm
      survival increased from 8.9% (39/440) to 14.4% (250/1,734; adjusted odds ratio
      [aOR] = 2.22; 95% CI 1.47 to 3.34). Survival with favorable neurologic outcome
      (cerebral performance category score = 1 or 2) increased from 5.9% (26/439) to
      8.9% (153/1,727; aOR = 2.26 [95% CI 1.37, 3.73]). For witnessed shockable
      rhythms, survival increased from 21.4% (21/98) to 39.2% (115/293; aOR = 2.96 [95%
      CI 1.63, 5.38]) and cerebral performance category score = 1 or 2 increased from
      19.4% (19/98) to 29.8% (87/292; aOR = 2.12 [95% CI 1.14, 3.93]). CONCLUSION:
      Implementation of a statewide system of cardiac receiving centers and EMS bypass
      was independently associated with increased overall survival and favorable
      neurologic outcome. In addition, these outcomes improved among patients with
      witnessed shockable rhythms.

PMID- 25064742
TI  - The effect of ketamine on intracranial and cerebral perfusion pressure and health
      outcomes: a systematic review.
AB  - STUDY OBJECTIVE: We synthesize the available evidence on the effect of ketamine
      on intracranial and cerebral perfusion pressures, neurologic outcomes, ICU length
      of stay, and mortality. METHODS: We developed a systematic search strategy and
      applied it to 6 electronic reference databases. We completed a gray literature
      search and searched medical journals as well as the bibliographies of relevant
      articles. We included randomized and nonrandomized prospective studies that
      compared the effect of ketamine with another intravenous sedative in intubated
      patients and reported at least 1 outcome of interest. Two authors independently
      performed title, abstract, and full-text reviews, and abstracted data from all
      studies, using standardized forms. Data from randomized controlled trials and
      prospective studies were synthesized in a qualitative manner because the study
      designs, patient populations, reported outcomes, and follow-up periods were
      heterogeneous. We used the Jadad score and Cochrane Risk of Bias tool to assess
      study quality. RESULTS: We retrieved 4,896 titles, of which 10 studies met our
      inclusion criteria, reporting data on 953 patients. One study was deemed at low
      risk of bias in all quality assessment domains. All others were at high risk in
      at least 1 domain. Two of 8 studies reported small reductions in intracranial
      pressure within 10 minutes of ketamine administration, and 2 studies reported an
      increase. None of the studies reported significant differences in cerebral
      perfusion pressure, neurologic outcomes, ICU length of stay, or mortality.
      CONCLUSION: According to the available literature, the use of ketamine in
      critically ill patients does not appear to adversely affect patient outcomes.

PMID- 25064743
TI  - Outcomes of thalassemia patients undergoing hematopoietic stem cell
      transplantation by using a standard myeloablative versus a novel reduced-toxicity
      conditioning regimen according to a new risk stratification.
AB  - Improving outcomes among class 3 thalassemia patients receiving allogeneic
      hematopoietic stem cell transplantations (HSCT) remains a challenge. Before HSCT,
      patients who were >= 7 years old and had a liver size >= 5 cm constitute what the
      Center for International Blood and Marrow Transplant Research defined as a very
      high-risk subset of a conventional high-risk class 3 group (here referred to as
      class 3 HR). We performed HSCT in 98 patients with related and unrelated donor
      stem cells. Seventy-six of the patients with age < 10 years received the more
      conventional myeloablative conditioning (MAC) regimen (cyclophosphamide,
      busulfan, +/- fludarabine); the remaining 22 patients with age >= 10 years and
      hepatomegaly (class 3 HR), and in several instances additional comorbidity
      problems, underwent HSCT with a novel reduced-toxicity conditioning (RTC) regimen
      (fludarabine and busulfan). We then compared the outcomes between these 2 groups
      (MAC versus RTC). Event-free survival (86% versus 90%) and overall survival (95%
      versus 90%) were not significantly different between the respective groups;
      however, there was a higher incidence of serious treatment-related complications
      in the MAC group, and although we experienced 6 graft failures in the MAC group
      (8%), there were none in the RTC group. Based on these results, we suggest that
      (1) class 3 HR thalassemia patients can safely receive HSCT with our novel RTC
      regimen and achieve the same excellent outcome as low/standard-risk thalassemia
      patients who received the standard MAC regimen, and further, (2) that this novel
      RTC approach should be tested in the low/standard-risk patient population. 

PMID- 25064745
TI  - Calcineurin inhibitor--free graft-versus-host disease prophylaxis with post
      transplantation cyclophosphamide and brief-course sirolimus following reduced
      intensity peripheral blood stem cell transplantation.
AB  - Calcineurin inhibitors (CNIs) form the foundation of current graft-versus-host
      disease (GVHD) prophylaxis regimens. We hypothesized that a CNI-free regimen
      consisting of post-transplantation cyclophosphamide (PTCy) and brief-course
      sirolimus would reduce chronic GVHD and nonrelapse mortality (NRM) after reduced
      intensity conditioning allogeneic peripheral blood stem cell transplantation
      (PBSCT). Twenty-six patients (median age, 61 years) underwent unmanipulated PBSCT
      from an 8/8 locus-matched donor (matched related donor, n = 17; natched unrelated
      donor, n = 9). GVHD prophylaxis consisted of PTCy and brief-course sirolimus.
      Donor engraftment occurred in all patients. The cumulative incidence (CI) of
      grade II-IV acute GVHD, grade III-IV acute GVHD, and chronic GVHD was 46%, 15%,
      and 31% respectively. One-year NRM was 4%. The median time to immunosuppression
      discontinuation was day +138. With a median follow-up of 20 months, the estimated
      2-year overall survival was 71%, estimated disease-free survival was 64%, and
      estimated relapse incidence was 32%. In patients with a lymphoid malignancy (eg,
      chronic lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease), 2-year
      disease-free survival was 100%, and there were no relapses. Good immune
      reconstitution was evidenced by low cytomegalovirus reactivation rate of 21% (4
      of 19 at-risk patients). GVHD prophylaxis with PTCy and sirolimus achieves
      consistent donor engraftment, low rates of chronic GVHD and NRM, and excellent
      outcomes in recipients of HLA-identical related and unrelated donor allogeneic
      PBSCT.

PMID- 25064744
TI  - Synergistic effect of major histocompatibility complex class I-related chain a
      and human leukocyte antigen-DPB1 mismatches in association with acute graft
      versus-host disease after unrelated donor hematopoietic stem cell
      transplantation.
AB  - The clinical relevance of mismatches at the MHC class I-related chain A (MICA) in
      hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated
      the association of MICA donor/recipient mismatch and whether there is an
      interaction between these and HLA-DPB1 mismatch on clinical outcomes after
      unrelated donor HSCT. Our study included 227 patients who underwent unrelated
      donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177
      (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed
      using commercially available kits. In univariable analysis, the risk of grade II
      to IV acute graft-versus-host disease (GVHD) was greater for patients with MICA
      mismatch (hazard ratio [HR], 1.73; P = .02) than for those with HLA-DPB1 mismatch
      (HR, 1.62; P = .07). When MICA and HLA-DPB1 were assessed simultaneously,
      patients mismatched at both loci had the greatest risk (HR, 2.51; P < .01) and
      those mismatched at only 1 locus had somewhat greater risk (HR, 1.53; P = .12)
      than patients matched at both loci; this remained significant in multivariable
      analysis. The 100-day incidence was 66%, 45%, and 31%, respectively (P = .03).
      Results were similar for grade III and IV acute GVHD, with 100-day incidence 34%,
      16%, and 8% (P = .01). These results are clinically pertinent to donor selection
      strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are
      at increased risk for acute GVHD.

PMID- 25064746
TI  - Therapeutic benefit of bortezomib on acute graft-versus-host disease is tissue
      specific and is associated with interleukin-6 levels.
AB  - Bortezomib, a proteasome inhibitor capable of direct antitumor effects, has been
      shown to prevent acute graft-versus-host disease (GVHD) when administered in a
      short course immediately after bone marrow transplantation (BMT) in mice.
      However, when bortezomib is given continuously, CD4(+) T cell-mediated
      gastrointestinal tract damage increases GVHD mortality. To investigate the
      protective effects of bortezomib on other organs, we used a CD8-dependent acute
      GVHD (aGVHD) model of C3H.SW donor T cells engrafted into irradiated C57BL/6
      recipients (minor MHC mismatch), which lack significant gut GVHD. Our data in
      this model show that bortezomib can be given continuously to prevent and treat
      aGVHD mediated by CD8(+) T cells, but this effect is organ specific, such that
      only skin, and not liver, protection was observed. Despite the lack of hepatic
      protection, bortezomib still significantly improved survival, primarily because
      of its skin protection. Reduced skin GVHD by bortezomib was correlated with
      reduced serum and skin IL-6 levels. Administration of a blocking IL-6 antibody in
      this model also resulted in similar cutaneous GVHD protection. These results
      indicate that bortezomib or blockade of IL-6 may prevent CD8(+) T cell-mediated
      cutaneous acute GVHD. 

PMID- 25064747
TI  - Hospital length of stay in the first 100 days after allogeneic hematopoietic cell
      transplantation for acute leukemia in remission: comparison among alternative
      graft sources.
AB  - Several studies have shown comparable survival outcomes with different graft
      sources, but the relative resource needs of hematopoietic cell transplantation
      (HCT) by graft source have not been well studied. We compared total hospital
      length of stay in the first 100 days after HCT in 1577 patients with acute
      leukemia in remission who underwent HCT with an umbilical cord blood (UCB),
      matched unrelated donor (MUD), or mismatched unrelated donor (MMUD) graft between
      2008 and 2011. To ensure a relatively homogenous study population, the analysis
      was limited to patients with acute myelogenous leukemia and acute lymphoblastic
      leukemia in first or second complete remission who underwent HCT in the United
      States. To account for early deaths, we compared the number of days alive and out
      of the hospital in the first 100 days post-transplantation. For children who
      received myeloablative conditioning, the median time alive and out of the
      hospital in the first 100 days was 50 days for single UCB recipients, 54 days for
      double UCB recipients, and 60 days for MUD bone marrow (BM) recipients. In
      multivariate analysis, use of UCB was significantly associated with fewer days
      alive and out of the hospital compared with MUD BM. For adults who received
      myeloablative conditioning, the median time alive and out of the hospital in
      first 100 days was 52 days for single UCB recipients, 55 days for double UCB
      recipients, 69 days for MUD BM recipients, 75 days for MUD peripheral blood stem
      cell (PBSC) recipients, 63 days for MMUD BM recipients, and 67 days for MMUD PBSC
      recipients. In multivariate analysis, UCB and MMUD BM recipients had fewer days
      alive and out of the hospital compared with recipients of other graft sources.
      For adults who received a reduced-intensity preparative regimen, the median time
      alive and out of the hospital during the first 100 days was 65 days for single
      UCB recipients, 63 days for double UCB recipients, 79 days for MUD PBSC
      recipients, and 79 days for MMUD PBSC recipients. Similar to the other 2 groups,
      receipt of UCB was associated with a fewer days alive and out of the hospital. In
      conclusion, length of stay in the first 100 days post-transplantation varies by
      graft source and is longer for UCB HCT recipients. These data provide insight
      into the resource needs of patients who undergo HCT with these various graft
      sources.

PMID- 25064748
TI  - Will post-transplantation cell therapies for pediatric patients become standard
      of care?
AB  - Although allogeneic hematopoietic stem cell transplantation (HSCT) is a curative
      approach for many pediatric patients with hematologic malignancies and some
      nonmalignant disorders, some critical obstacles remain to be overcome, including
      relapse, engraftment failure, graft-versus-host disease (GVHD), and infection.
      Harnessing the immune system to induce a graft-versus-tumor effect or rapidly
      restore antiviral immunity through the use of donor lymphocyte infusion (DLI) has
      been remarkably successful in some settings. Unfortunately, however, the
      responses to DLI can be variable, and GVHD is common. Thus, manipulations to
      minimize GVHD while restoring antiviral immunity and enhancing the graft-versus
      tumor effect are needed to improve outcomes after allogeneic HSCT. Cellular
      therapies, defined as treatment modalities in which hematopoietic or
      nonhematopoietic cells are used as therapeutic agents, offer this promise for
      improving outcomes post-HSCT. This review presents an overview of the field for
      pediatric cell therapies in the transplant setting and discusses how we can
      broaden applicability beyond phase I. 

PMID- 25064749
TI  - Binding and interaction of di- and tri-substituted organometallic triptycene
      palladium complexes with DNA.
AB  - Two triptycene-based ligands with pendant bromophenyl units have been prepared.
      These triptycene derivatives have been used as synthons for the synthesis of di
      and tri nuclear palladium complexes. The organic molecules and their
      corresponding organometallic complexes have been fully characterized using
      nuclear magnetic resonance (NMR), infrared (IR) spectroscopy and mass
      spectrometry. The mode of binding and effect of the complexes on pUC19 plasmid,
      calf thymus DNA and oligomer duplex DNA have been investigated by a host of
      analytical methods. The complexes brought about unwinding of supercoiled plasmid
      and the unwinding angle was found to be related to the binding affinity of the
      complexes with DNA, where both these parameters were guided by the structure of
      the complexes. Concentration-dependent inhibition of endonuclease activity of
      SspI and BamHI by the complexes indicates preference for G/C sequence for binding
      to DNA. However, neither the complexes did not introduce any cleavage at abasic
      site in oligomer duplex DNA, nor they created linear form of the plasmid upon co
      incubation with the DNA samples. The interactions of the complexes with DNA were
      found to be strongly guided by the structure of the complexes, where
      intercalation as well as groove binding was observed, without inflicting any
      damage to the DNA. The mode of interaction of the complexes with DNA was further
      confirmed by isothermal calorimetry. 

PMID- 25064751
TI  - Repair of full-thickness rotator cuff tears in patients aged younger than 55
      years.
AB  - PURPOSE: The purpose of this study was to conduct a systematic review of the
      available evidence regarding clinical outcomes after open or arthroscopic repair
      of full-thickness rotator cuff tears in young patients. METHODS: Medline, PubMed,
      and Embase were reviewed to find all studies examining full-thickness rotator
      cuff repairs in patients aged younger than 55 years and with a minimum of 1 year
      of follow-up. RESULTS: We found 7 studies that met the inclusion criteria. The
      mean patient age was 41.7 years (range, 16.2 to 54 years), and the mean time from
      injury was 66.1 months. Eighty-one percent of the included patients had a
      traumatic tear. The rotator cuff repair was supplemented by acromioplasty in
      96.6% of patients, distal clavicle resection in 34.6%, and biceps tenodesis in
      16.1%. Postoperative American Shoulder and Elbow Surgeons Standardized Shoulder
      Assessment was the most commonly reported outcome score, with a mean
      postoperative score of 82.0 (4 studies). Improvement was shown in all studies
      that reported on postoperative strength. All studies that assessed pain showed an
      improvement in the postoperative setting. Overall, 82% of the shoulders had
      satisfactory results. CONCLUSIONS: Full-thickness rotator cuff tears in patients
      aged younger than 55 years are mostly traumatic in origin and respond well to
      open and arthroscopic rotator cuff repair, as shown by good patient-reported
      outcomes, significant pain relief, improvement in strength, and high satisfaction
      postoperatively. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV
      studies.

PMID- 25064750
TI  - Involvement of ferryl in the reaction between nitrite and the oxy forms of
      globins.
AB  - The reaction between nitrite and the oxy forms of globins has complex
      autocatalytic kinetics with several branching steps and evolves through chain
      reactions mediated by reactive species (including radicals) such as hydrogen
      peroxide, ferryl and nitrogen dioxide, starting with a lag phase, after which it
      proceeds onto an autocatalytic phase. Reported here are UV-Vis spectra collected
      upon stopped-flow mixing of myoglobin with a supraphysiological excess of
      nitrite. The best fit to the experimental data follows an A -> B -> C reaction
      scheme involving the formation of a short-lived intermediate identified as
      ferryl. This is consistent with a mechanism where nitrite binds to oxy myoglobin
      to generate an undetectable ferrous-peroxynitrate intermediate, whose decay leads
      to nitrate and ferryl. The ferryl is then reduced to met by the excess nitrite.
      DFT calculations reveal an essentially barrierless reaction between nitrite and
      the oxy heme, with a notable outer-sphere component; the resulting metastable
      ferrous-peroxynitrate adduct is found to feature a very low barrier towards
      nitrate liberation, with ferryl as a final product-in good agreement with
      experiment. 

PMID- 25064752
TI  - Biomechanical comparison between the rectangular-tunnel and the round-tunnel
      anterior cruciate ligament reconstruction procedures with a bone-patellar tendon
      bone graft.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of 2
      anterior cruciate ligament (ACL) reconstruction techniques using a bone-patellar
      tendon-bone (BPTB) graft with femoral tunnel, either a rectangular tunnel (RET)
      or a round tunnel (ROT). METHODS: For experiment 1, nine fresh-frozen human
      cadaveric knees were tested with a robotic/universal force-moment sensor system
      to determine the initial optimal tension: the amount of graft tension at 15
      degrees  of flexion most closely resembling the anterior laxity of a normal knee.
      The value was estimated by repeatedly measuring anterior laxity when 100 N of
      anteroposterior drawer load was applied to the knees at 30 degrees  of flexion
      after RET ACL or ROT ACL reconstruction. For experiment 2, six fresh-frozen human
      cadaveric knees were selected. On the basis of the initial tension determined in
      experiment 1, RET ACL reconstruction was conducted with the graft tensioned to 10
      N, followed by ROT ACL reconstruction on the same knee at 40 N of initial
      tension, and the biomechanical efficacy of the 2 methods was compared. RESULTS:
      For experiment 1, the mean laxity match tension at 15 degrees  of flexion was 8.6
      +/- 4.8 N and 34.8 +/- 9.2 N for RET- and ROT-reconstructed knees, respectively.
      For experiment 2, both RET and ROT ACL reconstructions were successful in
      controlling anterior tibial translation under anterior tibial loads, with the
      graft initially tensioned to 10 N in the former and to 40 N in the latter.
      However, the greater tensioning in ROT reconstruction led to proximal, posterior,
      and lateral displacement of the tibia along with its external and valgus
      rotation. CONCLUSIONS: The RET ACL-reconstructed knee more closely resembled the
      normal knee in biomechanical behavior. Although ROT reconstruction successfully
      controlled anterior translation with greater initial tensioning to the graft, the
      normal positional relation between the tibia and femur was impaired. CLINICAL
      RELEVANCE: Rectangular femoral ACL fixation constructs and grafts may prove more
      efficacious at restoring in vivo ACL kinematics than round femoral tunnels.

PMID- 25064753
TI  - Clinical and functional outcomes after anterior cruciate ligament reconstruction
      using cortical button fixation versus transfemoral suspensory fixation: a
      systematic review of randomized controlled trials.
AB  - PURPOSE: To compare clinical and functional outcomes after anterior cruciate
      ligament (ACL) reconstruction using cortical button versus transfemoral
      suspensory fixation. METHODS: This systematic review was conducted following the
      Cochrane handbook guidelines and PROSPERO registration. Only Level I and II
      randomized controlled trials comparing cortical button and transfemoral
      suspensory fixation in hamstring ACL reconstruction were included. A literature
      search was performed using electronic databases. The methodologic quality of
      included studies was assessed using The Cochrane Collaboration's risk-of-bias
      tool. All outcomes reported by each study were evaluated. Primary outcome
      measures were postoperative International Knee Documentation Committee (IKDC) and
      Lysholm knee scores. Statistical analysis was performed using RevMan software
      (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). Dichotomous
      data were reported as risk ratio and 95% confidence intervals. Heterogeneity was
      assessed using I(2). RESULTS: Five studies involving 317 patients were included.
      The mean follow-up period was 21.7 +/- 7.0 months (range, 12 to 38 months). The
      mean age of participants was 26.7 +/- 1.89 years (range, 16 to 48 years). The
      Lysholm score, Tegner activity score, and IKDC score were compiled. Clinical
      assessment was performed by Lachman testing, assessment of side-to-side
      differences on KT-1000 (MEDmetric, San Diego, CA) testing, and measurements of
      thigh atrophy, as well as imaging (radiography and computed tomography) to assess
      for femoral tunnel widening. Pooled statistical analysis was possible only for
      postoperative IKDC and Lysholm scores. No significant differences were found
      between the cortical button and transfemoral fixation groups. Included studies
      did not report differences in clinical outcomes between the 2 groups.
      Radiographic results suggest increased femoral tunnel widening in the cortical
      button group. However, tunnel widening was not found to affect clinical results.
      CONCLUSIONS: The present evidence suggests that there are no short- to medium
      term differences in knee-specific outcome measures between patients treated with
      cortical button femoral graft fixation and those treated with suspensory
      transfemoral fixation when undergoing ACL reconstruction. In addition, radiologic
      evidence of tunnel widening does not seem to affect short- to medium-term
      clinical outcomes. LEVEL OF EVIDENCE: Level II, systematic review of Level I and
      II studies.

PMID- 25064754
TI  - Arthroscopic surgery for synovial chondromatosis of the hip: a systematic review
      of rates and predisposing factors for recurrence.
AB  - PURPOSE: Synovial chondromatosis of the hip is a benign condition whereby pain
      and functional limitations occur due to numerous intra-articular osteochondral
      fragments produced by a metaplastic synovium. Recurrence not only worsens
      morbidity but may lead to malignant transformation. With reported recurrence
      rates as high as 22% by open surgical approaches and given the increasing use of
      hip arthroscopy for the treatment of synovial chondromatosis, we sought to
      quantify the recurrence rate after arthroscopy, as well as identify predisposing
      factors for recurrence. METHODS: Using predetermined inclusion criteria, 3
      electronic databases--Embase, Medline, and PubMed-were searched for relevant
      articles addressing arthroscopic surgery for synovial chondromatosis of the hip
      across all available dates up to and including February 16, 2014. A hand search
      of the reference sections of the included studies was also completed. Article
      screening was conducted in duplicate. Reviewer agreement statistics and
      descriptive statistics of the included studies are presented. RESULTS: From an
      initial retrieval of 2,542 studies, 14 studies satisfied the criteria for
      inclusion. A total of 197 patients (age range, 13 to 81 years) underwent hip
      arthroscopy for removal of intra-articular osteochondral fragments and
      synovectomy to alleviate both mechanical symptoms and pain. Follow-up periods
      ranged from 1 to 184 months, with approximately 7.6% of patients (15 of 197) lost
      to follow-up. The recurrence rate after hip arthroscopy was 7.1% (14 of 197), and
      the rate of minor complications, such as perineal and pedal neurapraxia, was 1%.
      CONCLUSIONS: For synovial chondromatosis of the hip, arthroscopic removal of
      osteochondral fragments with synovectomy is both safe and effective, with a mean
      recurrence rate of 7.1%. LEVEL OF EVIDENCE: Level IV, systematic review of Level
      IV studies.

PMID- 25064755
TI  - New findings in hip capsular anatomy: dimensions of capsular thickness and
      pericapsular contributions.
AB  - PURPOSE: The purpose of this investigation was to provide a detailed description
      of the anatomy of the hip capsule and pericapsular structures. METHODS:
      Dissections were performed on 11 nonpaired, fresh-frozen cadaveric hips by 2
      independent observers: 1 fellowship-trained orthopaedic total joint surgeon and 1
      chief orthopaedic surgery resident. Documentation of capsular thickness, origins,
      insertions, and attachments to pericapsular structures including the abductors,
      rectus femoris, piriformis, short external rotators, and iliocapsularis muscles
      was performed. Tendinous insertions of the surrounding pericapsular muscles were
      measured according to size and distance from reproducible osseous landmarks.
      RESULTS: The capsule is thickest near the acetabular origin at the
      posterosuperior and superior hemi-quadrants and is thinnest near the femoral
      insertion in the posterior and posteroinferior hemi-quadrants. The
      iliocapsularis, indirect head of the rectus, conjoint, obturator externus, and
      gluteus minimus tendons all show consistent capsular contributions, whereas the
      piriformis does not have a capsular attachment. Osseous landmarks for tendinous
      attachments are defined and illustrated. The inter-relation of these structures
      is complex, yet their relations to the anterior hip capsule and contributions to
      its thickness are predictable. CONCLUSIONS: The dynamic pericapsular structures
      pertinent to the hip arthroscopist include the iliocapsularis, gluteus minimus,
      and reflected head of the rectus femoris. At the acetabulum, the thickest region
      of the capsule is posterosuperior and superolateral. At the femoral insertion,
      the thickest region is anterior. CLINICAL RELEVANCE: Knowledge of the intricate
      relation between the hip capsule and pericapsular structures presented here will
      be useful for surgeons as they perform the precise and specific capsular releases
      required during hip arthroscopy. Our anatomic findings contribute important
      qualitative data that build on the recent literature regarding the importance of
      capsular management during hip arthroscopy to postoperative hip stability.

PMID- 25064756
TI  - Effect of body mass index on patients with multiligamentous knee injuries.
AB  - PURPOSE: Our goal was to evaluate the impact of body mass index (BMI) on
      complications and associated injuries in patients undergoing surgical treatment
      for multiligamentous knee injuries (MLKIs). METHODS: Over a period of 10 years,
      126 MLKIs (123 patients) were included in the study. The inclusion criteria were
      (1) injury to 2 or more knee ligaments, (2) multiligament repair and/or
      reconstruction performed by 1 of 3 sports medicine orthopaedic surgeons at our
      institution, and (3) minimum of 1 year of follow-up. A chart review was performed
      to collect demographic data, mechanism of injury, ligaments involved,
      complications, and associated neurovascular injuries. Lastly, patients were
      divided by BMI into non-obese (<30 kg/m(2)) and obese (>=30 kg/m(2)) groups.
      RESULTS: Of the 126 MLKIs, 87 occurred in non-obese patients and 39 occurred in
      obese patients. Surgical complication rates for non-obese and obese patients were
      8.05% and 15.4%, respectively (P = .21). Revisions were needed in 8.05% and 5.1%
      of patients in these groups, respectively (P = .72). Three wound complications
      were found in the obese group only. Vascular injuries were found in 2.3% and 7.7%
      of patients in the non-obese and obese groups, respectively (P = .17). The rates
      of nerve injuries were 11.49% and 20.51%, respectively (P = .18). Patients in the
      obese group were most likely to have an MLKI from low-energy mechanisms,
      disregarding sports-related injuries (51.28%, P = .02). Using a logistic model
      and BMI as a continuous variable, we found that a 1-unit increase in BMI
      increased the odds ratio of complications by 9.2%, with statistical significance
      (P = .0174). In addition, post hoc power analysis using previous literature
      showed that this study could produce satisfactory power. CONCLUSIONS: Our results
      indicate that (1) obese individuals are significantly more likely to have an MLKI
      caused by low-energy mechanisms and (2) complication rates increase by 9.2% for
      every 1-unit increase in BMI. LEVEL OF EVIDENCE: Level III, retrospective
      comparative study.

PMID- 25064757
TI  - Topographic variations in biomechanical and biochemical properties in the ankle
      joint: an in vitro bovine study evaluating native and engineered cartilage.
AB  - PURPOSE: The purposes of this study were to identify differences in the
      biomechanical and biochemical properties among the articulating surfaces of the
      ankle joint and to evaluate the functional and biological properties of
      engineered neocartilage generated using chondrocytes from different locations in
      the ankle joint. METHODS: The properties of the different topographies within the
      ankle joint (tibial plafond, talar dome, and distal fibula) were evaluated in 28
      specimens using 7 bovine ankles; the femoral condyle was used as a control.
      Chondrocytes from the same locations were used to form 28 neocartilage constructs
      by tissue engineering using an additional 7 bovine ankles. The functional
      properties of neocartilage were compared with native tissue values. RESULTS:
      Articular cartilage from the tibial plafond, distal fibula, talar dome, and
      femoral condyle exhibited Young modulus values of 4.8 +/- 0.5 MPa, 3.9 +/- 0.1
      MPa, 1.7 +/- 0.2 MPa, and 4.0 +/- 0.5 MPa, respectively. The compressive
      properties of the corresponding tissues were 370 +/- 22 kPa, 242 +/- 18 kPa, 255
      +/- 26 kPa, and 274 +/- 18 kPa, respectively. The tibial plafond exhibited 3-fold
      higher tensile properties and 2-fold higher compressive and shear moduli compared
      with its articulating talar dome; the same disparity was observed in
      neocartilage. Similar trends were detected in biochemical data for both native
      and engineered tissues. CONCLUSIONS: The cartilage properties of the various
      topographic locations within the ankle are significantly different. In
      particular, the opposing articulating surfaces of the ankle have significantly
      different biomechanical and biochemical properties. The disparity between tibial
      plafond and talar dome cartilage and chondrocytes warrants further evaluation in
      clinical studies to evaluate their exact role in the pathogenesis of ankle
      lesions. CLINICAL RELEVANCE: Therapeutic modalities for cartilage lesions need to
      consider the exact topographic source of the cells or cartilage grafts used.
      Furthermore, the capacity of generating neocartilage implants from location
      specific chondrocytes of the ankle joint may be used in the future as a tool for
      the treatment of chondral lesions.

PMID- 25064758
TI  - An analysis of technical aspects of the arthroscopic Bankart procedure as
      performed in the United States.
AB  - PURPOSE: The purpose of this study was to investigate the intersurgeon variation
      in technical aspects of performing an arthroscopic Bankart repair. METHODS: A
      unique approach with experienced equipment representatives from 3 different
      arthroscopic companies was used. Experienced representatives were identified by
      DePuy Mitek, Smith & Nephew, and Arthrex and filled out questionnaires on how
      their surgeons performed arthroscopic Bankart procedures. This was performed in a
      blinded fashion with no knowledge of the identities of the specific surgeons or
      representatives by us. A video on different aspects of the procedure was observed
      by each representative before filling out the questionnaire to help standardize
      responses. Data were collected using REDCap (Research Electronic Data Capture).
      Data were analyzed as an infrequent observation with 0% to 30% of representatives
      reporting the observation; sometimes, 31% to 70% reporting the observation; and
      often, greater than 70% of representatives reporting. RESULTS: Seventy-six
      percent of representatives had 6 or more years of arthroscopic experience. Forty
      three percent of representatives reported that their surgeons use 3 portals for
      the procedure often. Forty-four percent reported that viewing was performed
      exclusively from the posterior portal while the surgeon was performing the
      repair. Seventy-three percent reported that the Hill-Sachs lesion was observed
      often, and 61% reported that the posterior labrum was evaluated often before the
      repair. Only 25% of representatives reported that the Bankart lesion was
      extensively released and mobilized often. Thirty-three percent reported 3 anchors
      as being used often. Seventy-five percent reported biocomposite anchors as being
      used often. Single-loaded anchors were reported as being used often by 47%.
      Eighty-one percent reported that sutures were placed in a simple fashion. Eighty
      three percent reported the use of any posterior sutures or anchors for additional
      plication as infrequent. CONCLUSIONS: There is significant variation in
      performance of the arthroscopic Bankart repair in the United States. Areas of
      concern include completeness of the diagnostic examination, the adequacy of
      capsulolabral mobilization, variation in the use of accessory portals, and
      inconsistent use of additional capsular or labral plication or fixation.

PMID- 25064759
TI  - Arthroscopic femoral neck osteoplasty in slipped capital femoral epiphysis.
AB  - PURPOSE: To investigate the outcomes of arthroscopic femoral neck osteoplasty in
      patients with slipped capital femoral epiphysis (SCFE)-related impingement.
      METHODS: We retrospectively reviewed 37 consecutive patients (40 hips; 19 male
      and 18 female patients; age range, 10 to 19 years) with SCFE who underwent hip
      arthroscopy for femoral neck osteoplasty over a 4-year period. Six hips were
      excluded because of the severity of the slip or conversion to an open procedure.
      The preoperative and postoperative slip angle, alpha angle, and internal rotation
      in flexion were compared. Patients were evaluated for pain, functional
      limitations, and obligatory external rotation deformity (OERD) at each follow-up
      visit. The mean follow-up period was 22 months (range, 12 to 56 months). RESULTS:
      We analyzed the results of 34 hips. Adequate distraction could not be obtained
      initially in 7 hips. The labral and acetabular cartilage damage appeared to be
      from crushing and abrasion from the bony prominence of the neck. The goals of
      complete pain relief and correction of OERD were achieved in 88% of the hips.
      OERD and pain persisted in 2 hips, and 2 patients had residual pain despite good
      motion. There was a statistically significant improvement in alpha angle (from
      88.22 degrees  and 56.91 degrees , P < .0001) and internal rotation in flexion
      (from -21.53 degrees  to 10.28 degrees , P < .0001) with intervention.
      CONCLUSIONS: Arthroscopic femoral neck osteoplasty is effective in decreasing
      pain, the alpha angle, and OERD in mild to moderate SCFE. Morbid obesity,
      scarring from previous surgery, and the presence of screws in the anterior neck
      presented challenges to the arthroscopic technique. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 25064761
TI  - Evaluation of real time PCR assays for the detection and enumeration of
      enterohemorrhagic Escherichia coli directly from cattle feces.
AB  - Shiga toxin-producing Escherichia coli are a growing concern in the area of food
      safety, and the United States Department of Agriculture Food Safety and
      Inspection Service has identified the serotypes O26, O45, O103, O111, O121, O145,
      and O157 as adulterants in certain types of raw beef. The most relevant to human
      disease are the enterohemorrhagic E. coli (EHEC) strains that possess intimin
      (eae), Shiga toxin 1 and/or 2 (stx1-2), and in most cases the conserved pO157 or
      pO157 like virulence plasmid. Contamination of raw beef with EHEC is likely to
      occur via the transfer of cattle feces on hides to the carcass. To detect EHEC
      directly from cattle feces, we evaluated the utility of a multiplex real time PCR
      assay that targets the EHEC associated gene target ecf1 in combination with eae
      and stx1-2. Our assay had an increased sensitivity and provided a reliable limit
      of detection (LOD) of 1.25*10(3)colony-forming unitspermL (CFUs/mL) in an EHEC
      spiked fecal background. In addition, we evaluated the use of a duplex qPCR assay
      using ecf1 for the enumeration of total EHEC directly from cattle feces. The
      reliable limit of quantification (LOQ) was determined to be 1.25*10(3)CFUs/mL.
      Our assay requires minimal sample processing and provides LOD and LOQ of EHEC
      directly from cattle feces that are the lowest reported. The application of this
      assay towards the identification of cattle shedding EHEC at a level above
      1.25*10(3)CFUs/mL could be a first line of defense in identifying cattle shedding
      these pathogens. 

PMID- 25064760
TI  - Ameliorating effects of Juzentaihoto on restraint stress and P. gingivalis
      induced alveolar bone loss.
AB  - OBJECTIVE: Juzentaihoto (JTX) is a traditional Japanese medicine that consists of
      10 herbs. The purpose of this study was to evaluate the efficacy of multi-herbal
      medicine JTX as a preventive and therapeutic drug for periodontal bone resorption
      and for reducing restraint stress. MATERIALS AND METHODS: Porphyromonas
      gingivalis ATCC 33277 was used for testing the antibacterial activity of JTX and
      a rat experimental periodontitis model. To evaluate the effect of JTX against P.
      gingivalis infection, we determined the differences in alveolar bone loss among
      experimental groups. The concentrations of adrenocorticotropic hormones were
      measured as stress markers, and atrophy of the thymus and spleen was assessed.
      RESULTS: JTX had antibacterial activity against P. gingivalis ATCC 33277. JTX
      treatment of mouse bone marrow cells at a concentration of 0.1 MUg/ml
      significantly inhibited osteoclast formation. Administration of JTX to rats with
      P. gingivalis infection and restraint stress significantly reduced alveolar bone
      loss compared with the case with just the combination of P. gingivalis infection
      and restraint stress. In the restrained groups, stress markers were elevated, and
      the thymus and spleen were atrophied. The groups with administration of JTX
      showed not only inhibition of the decrease of weight but also normalization of
      corticosterone and cortisol values. CONCLUSION: JTX effectively inhibited
      restraint stress and osteoclastogenesis. It appears that the effects of JTX
      inhibit the destruction of periodontal tissue by suppressing stress. Our study
      demonstrated that JTX affects the correlation between restraint stress and
      periodontitis.

PMID- 25064762
TI  - Examining verbal memory on the Word Memory Test and California Verbal Learning
      Test-Second Edition.
AB  - This study compared the Word Memory Test (WMT) and California Verbal Learning
      Test-Second Edition (CVLT-II) in a sample (N = 76) of outpatient physiatry
      referrals who passed WMT validity indices. WMT and CVLT-II raw scores showed
      moderate to strong correlations. WMT scores were more likely to be below
      expectation than CVLT-II scores using norms from the respective test manuals.
      With impaired scores defined as 2 SDs below normative mean, the WMT and CVLT-II
      showed 67% overall agreement and kappa of 0.34. Forty percent of participants who
      scored within normal limits on the CVLT-II demonstrated an impaired score on the
      WMT. Despite evidence of utility, WMT memory subtests appear limited by current
      normative data. 

PMID- 25064763
TI  - Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb
      lymphoedema.
AB  - Chronic lower limb lymphoedema is a debilitating condition that may occur as a
      primary disorder or secondary to other conditions. Satisfactory visualization of
      the lymphatic vessels to aid diagnosis and surgical planning has been
      problematic. Historically, direct lymphography was used to visualize lymphatic
      vessels, although the significant surgical risks involved led to this being
      largely abandoned as a technique. Technetium-99m lymphoscintigraphy has been the
      mainstay of diagnosis for over two decades, but is hampered by inherently poor
      temporal and spatial resolution and limited anatomical detail. Contrast-enhanced
      magnetic resonance lymphography (MRL) is a relatively new technique that shows
      early promise in the evaluation of chronic lymphoedema. This article provides the
      procedural technique for lower limb MRL at both 1.5 and 3 T, discusses
      pathophysiology and classifications of lymphoedema, provides an overview of
      relevant lower limb lymphatic anatomy using MRL imaging, compares the various
      techniques used in the diagnosis of lower limb lymphoedema, shows common
      pathological MRL imaging findings, and describes alternative uses of MRL.
      Utilization of this technique will allow more accurate diagnosis and
      classification of patients suffering from lymphoedema.

PMID- 25064764
TI  - Soft-tissue masses in the abdominal wall.
AB  - Masses involving the abdominal wall arise from a large number of aetiologies.
      This article will describe a diagnostic approach, imaging features of the most
      common causes of abdominal wall masses, and highly specific characteristics of
      less common diseases. A diagnostic algorithm for abdominal wall masses combines
      clinical history and imaging appearances to classify lesions. 

PMID- 25064765
TI  - Serial publication of sections of the American Society of Hypertension (ASH) self
      assessment manual.

PMID- 25064766
TI  - Opportunities for multidisciplinary ASH clinical hypertension specialists in an
      era of population health and accountable care: ASH leadership message.
AB  - The ASH hypertension specialists and ASH clinical and comprehensive hypertension
      centers represent a continuum of expertise and capacity positioned to play a
      major role in advancing the Triple Aim, which includes improving the patient care
      experience, population health, and value in cardiovascular health promotion and
      disease prevention. The ASH hypertension specialists board is dedicated to
      testing and designating a broad range of qualified health care professionals as
      clinical hypertension specialists. A continuing partnership with ASH, recognizing
      the need for an appropriate firewall between education and testing, is essential
      in providing the education and training programs required to grow and sustain the
      specialized workforce required to translate current evidence and future advances
      in personalized medicine into better care for individuals, better health for
      populations, and better value for payers. Moreover, growth of the ASH
      hypertension registry has the potential to accelerate advances in education and
      patient care as noted previously. The ASH hypertension specialists board is
      excited about the opportunities available to a well-trained and collaborative
      multidisciplinary group of clinical hypertension specialists in an era of ACOs
      pursuing the Triple Aim.

PMID- 25064767
TI  - Cardiac myocyte sizes in right compared with left ventricle during overweight and
      hypertension.
AB  - Evidence is sparse concerning hypertrophy of cardiomyocytes in left and right
      ventricles (LV, RV). LV and RV from 105 forensic autopsies were weighed. Cross
      sectioned cardiac myocyte thicknesses were measured in hematoxylin and eosin
      stained paraffin sections. Overweight (OW) is body weight >104.3 kg and
      hypertension (HT) is mean arterial pressure >106.7 mm Hg assessed from renal
      histology. Mean RV weights and cardiomyocyte thicknesses held nearly perfect
      proportionality to the LV values. Exceptions to these patterns were (1) myocytes
      were slightly thicker than expected in RV of the 27 specimens with the smallest
      myocyte thicknesses; (2) weights were slightly greater than expected in RV of
      hypertensives; and (3) myocytes were slightly smaller than expected in RV of OW
      subjects. Myocyte hypertrophy appears to affect LV and RV equally, preserving
      constant proportionality between them in a number of conditions which include OW,
      HT, and perhaps some cardiomyopathies. Ischemic, valvular, and right ventricular
      disorders determined at autopsy are specifically omitted from this provisional
      conclusion. The three exceptions from this principle were of small magnitude and
      unimpressive statistical significance which calls for cautious interpretation.
      Neither OW nor HT appears to act predictably upon the heart as exclusively volume
      or pressure overload. 

PMID- 25064768
TI  - Low plasma renalase concentration in hypertensive patients after surgical repair
      of coarctation of aorta.
AB  - The study aimed to evaluate plasma renalase level, a recently discovered kidney
      derived catecholamine-metabolizing enzyme in patients after successful repair of
      aortic coarctation, with special consideration of arterial hypertension in the
      context of underlying process of arterial remodeling. This case-control study
      covered 50 consecutive patients after Dacron patch repair of aortic coarctation
      (31 men; median age 33 [26; 40]; age at surgery 10 [5; 16] years), matched in
      terms of age and gender with 50 controls. Both groups were stratified depending
      on the presence of hypertension and assessed in terms of renalase, C-reactive
      protein, and carotid intima-media thickness. Additionally ultrasound and
      tonometric markers of vascular remodeling were obtained in the study group.
      Hypertension was found in 21 patients (42%) in the study group and 29 (58%) in
      the control group (P = .11). Renalase level was significantly lower in patients
      in the study than control group (5825.1 vs. 6592.7 ng/mL; P = .041). Significant
      difference in terms of renalase concentration between hypertensive and
      normotensive patients was confirmed both in subjects with coarctation of aorta (P
      = .027) and in control group (P < .0001). Renalase level inversely correlated
      with serum creatinine (r = -0.36) and arterial blood pressure in the whole
      population, and with central systolic (r = -0.29) and diastolic pressure (r = 
      0.35) in study group. Multivariate regression revealed that serum creatinine and
      pulse pressure were independent predictors of renalase. Surgical intervention >7
      years was linked to lower renalase (P = .018) and unfavorable vascular
      parameters. Renalase level <4958 ng/mL accurately predicted presence of
      hypertension in patients after coarctation of aorta repair (odds ratio, 3.8; P =
      .032). Renalase deficiency is associated with the presence of hypertension in
      both patients after surgical repair of aortic coarctation and the control group.
      In coarctation of aorta, its action is probably parallel to underlying arterial
      remodeling. 

PMID- 25064770
TI  - Are video sharing web sites a useful source of information on hypertension?
AB  - Hypertension (HTN) is a prevalent and growing public health problem in the United
      States and worldwide. Video sharing Web sites such as YouTube could potentially
      influence patient behaviors via properties of interpersonal and mass media
      communication. We conducted this cross-sectional study to assess the accuracy and
      content of YouTube videos on HTN and understand how viewers interact with this
      online information. We analyzed 209 videos (31.57 hours) of which 63% were
      classified as useful, 33% as misleading, and 4% represented patient's personal
      experiences. Number of views per day and "likes" were significantly lower for
      useful videos. Approximately half the misleading videos contained product
      advertisements, 70% advocated unproven alternative treatments, and 91% targeted
      patients. Viewer engagement (number of views) was a poor predictor of usefulness
      and/or content whereas source of upload, and target audiences were good
      predictors of usefulness and/or content. Videos uploaded by university channels
      and/or professional organizations that targeted physicians had a 99.4% (P < .001)
      probability of being useful whereas videos uploaded by individuals with unknown
      credentials that targeted patients had a 21.2% (P < .001) probability of being
      useful. A majority of HTN-related videos on YouTube are useful. Viewer engagement
      is significantly higher with videos that contain misleading and/or erroneous
      information in comparison to videos that contain useful information. 

PMID- 25064769
TI  - Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid
      receptor antagonism or ENaC inhibition: an exploratory pilot study in African
      Americans.
AB  - An rs3890011 variant of CYP4A11, which is in linkage disequilibrium with the loss
      of-function variant rs1126742, is associated with hypertension in humans. In
      mice, Cyp4a deficiency results in salt-sensitive hypertension through activation
      of ENaC. We tested the hypothesis that the rs3890011 variant is associated with
      blood pressure response to drugs acting via the ENaC pathway. African Americans
      with volume-dependent, resistant hypertension were randomized to treatment with
      placebo, spironolactone, amiloride, or combination. Blood pressure responses were
      analyzed by CYP4A11 genotypes. Rs3890011 (GG:GC:CC = 20:35:28) and rs1126742
      (TT:TC:CC = 45:31:7) were in linkage disequilibrium (D' = 1, r = 0.561). Expected
      small number of rs1126742 CC homozygotes precluded analysis of the effect of this
      genotype on treatment responses. Spironolactone reduced blood pressure in
      rs3890011 GG and GC individuals, but not in CC homozygotes (P = .002), whereas
      amiloride reduced blood pressure similarly in all rs3890011 genotypes. The
      antihypertensive effects of spironolactone and amiloride were comparable in GG
      and GC participants, but only amiloride reduced pressure in CC homozygotes (-6.3
      +/- 7.3/-3.2 +/- 4.0 vs. +6.8 +/- 7.9/+4.8 +/- 8.6 mm Hg, P < .01/<.05). The
      aldosterone response to spironolactone was also blunted in the CC genotype. In
      individuals homozygous for the CYP4A11 rs3890011 C allele, blood pressure is
      resistant to mineralocorticoid receptor antagonism, but sensitive to ENaC
      inhibition, consistent with ENaC activation. Studies in a larger population are
      needed to replicate these findings. 

PMID- 25064771
TI  - Is systolic blood pressure below 150 mm Hg an appropriate goal for primary
      prevention of cardiovascular events among elderly population?
AB  - Recently, Joint National Committee has changed the optimal therapeutic goal of
      systolic blood pressure (SBP) up to 150 mm Hg for elderly population. We aimed to
      investigate impact of different blood pressure (BP) categories on risk of
      developing cardiovascular disease (CVD) and mortality among elderly. The present
      study included 1845 participants, aged >=60 years (mean age = 65 years), free of
      CVD at baseline, who had undergone health examinations between January 1999 and
      2001, and were followed up until March 2010. Cox proportional hazard regression
      was performed to assess the hazard ratios (HRs) of BP categories for CVD and
      mortality events, considering those with optimal BP (SBP <120 mm Hg and diastolic
      BP [DBP] <80 mm Hg) as reference. During a median of 10 years follow-up, 380
      cases of first CVD and 260 cases of mortality events occurred. In multivariable
      adjusted model, prehypertensive group (SBP between 120-129 mm Hg or DBP between
      80-85 mm Hg) could not predict CVD (HR, 0.87 [0.61-1.24]) nor mortality events
      (HR, 0.86 [0.58-1.34]). Those with SBP between 140 mm Hg and 150 mm Hg (group 3)
      were at higher risk for developing CVD (HR, 1.79 [1.17-2.74]), but there were no
      significant risk for total mortality (HR, 1.13 [0.65-1.97]). Hypertensive group
      (SBP >=150 mm Hg or DBP >=90 mm Hg or taking antihypertensive drugs) was
      associated with increased risk of both CVD (HR, 1.73 [1.24-2.42]) and mortality
      events (HR, 1.49 [1.00-2.23]).However, Joint National Committee 8 suggested no
      more benefit with lowering SBP <150 mm Hg, but the results of this study imply
      that those with SBP between 150 mm Hg and 140 mm Hg are still at elevated risk
      for CVD/coronary heart disease events. 

PMID- 25064772
TI  - Lowering blood pressure to prevent stroke recurrence: a systematic review of long
      term randomized trials.
AB  - Albeit hypertension is a leading risk factor for an initial stroke, the role of
      blood pressure (BP) lowering to prevent a subsequent stroke is controversial. The
      present systematic review searched randomized trials published from January 1990
      to January 2014 with the aim to assess antihypertensive treatment effects on
      recurrent stroke prevention. Seven randomized placebo-controlled trials enrolling
      49,518 patients, two randomized trials not placebo controlled comparing
      antihypertensive drugs, and one randomized trial that compared the effects of
      intensive systolic BP lowering with a more conservative systolic BP management,
      were identified. The placebo-controlled trials had substantial methodological
      differences, explaining the difficulties to compare their results. An important
      obstacle arises from the large dispersion in the window's time between the
      qualifying stroke and randomization. Another barrier is the variation among
      studies in the recruited patient's stroke subtypes. Differences between trials
      could not be attributed to disparity in lowering BP or to different degrees of no
      adherence. The American Heart Association/American Stroke Association stated that
      although an absolute target of BP level has not been clearly defined, a reduction
      in recurrent stroke has been associated with an average lowering of 10/5 mm Hg.
      It should be taken into account that it is not advisable to reduce BP levels to
      <120/80 mm Hg. It should carry out an individualized selection, based on
      demographic characteristics and comorbidities (cardiovascular disease, diabetes
      mellitus, and chronic disease) among diuretics, angiotensin converting enzyme
      inhibitors, angiotensin II receptor blockers, or calcium channel blockers. 

PMID- 25064773
TI  - Attempts to define the risk of elevated blood pressure.

PMID- 25064774
TI  - Physiology: hemodynamics, endothelial function, renin-angiotensin-aldosterone
      system, sympathetic nervous system.

PMID- 25064775
TI  - Outcomes with individual versus group physical therapy for treating urinary
      incontinence and low back pain: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: To evaluate the existing evidence comparing the outcomes of
      rehabilitation conducted in a group setting and individual therapy for patients
      receiving rehabilitation. DATA SOURCES: Electronic databases MEDLINE, CINAHL,
      EMBASE, PEDro, and OT Seeker were searched from the earliest date possible to
      July 2013. Additional references were identified by manual scanning of reference
      lists. STUDY SELECTION: Randomized controlled trials investigating the effect of
      group therapy compared with individual therapy for patients receiving
      rehabilitation were included for review. Two reviewers independently applied the
      inclusion and exclusion criteria to identify included articles. Initial search
      identified 1527 potential articles, of which 16 trials with 2337 participants
      were included in the final review. DATA EXTRACTION: Data extraction was completed
      for all included trials by one reviewer, using a customized data extraction form.
      Data were checked for accuracy by a second reviewer. Trials were independently
      assessed by 2 reviewers for methodological quality using the PEDro scale. DATA
      SYNTHESIS: Trials meeting inclusion criteria had been conducted in back pain (n=6
      studies), urinary incontinence (n=5), learning disability (n=2), hearing loss
      (n=1), joint replacement (n=1), and aphasia (n=1). Meta-analysis of physical
      therapy trials in back pain and urinary incontinence reporting sufficient
      homogeneous data showed no significant difference in outcomes for group versus
      individual therapy. These results were also supported by qualitative analysis of
      the remaining studies in these populations, but there is insufficient evidence to
      draw conclusions regarding other clinical areas. CONCLUSIONS: Evidence shows that
      providing rehabilitation in a group format results in equivalent clinical
      outcomes to provision of similar therapy in an individual format in the treatment
      of back pain and urinary incontinence. There is currently insufficient evidence
      to draw similar conclusions in other populations or fields of rehabilitation.

PMID- 25064776
TI  - Determining the most robust dimensional structure of categories from the
      international classification of functioning, disability and health across
      subgroups of persons with spinal cord injury to build the basis for future
      clinical measures.
AB  - OBJECTIVE: To determine the most robust dimensional structure of the
      International Classification of Functioning, Disability and Health (ICF)
      categories relevant to spinal cord injury (SCI) across subgroups of lesion level,
      health care context, sex, age, and resources of the country. DESIGN: A
      multidimensional between-item response Rasch model was used. The choice of the
      dimensions was conceptually driven using the ICF components from the functioning
      chapters and splits of the activity and participation component described in the
      ICF. SETTING: Secondary analysis of data from an international, cross-sectional,
      multicentric study for the Development of ICF Core Sets for Spinal Cord Injury.
      PARTICIPANTS: Persons with SCI (N=1048) from the early postacute and long-term
      living context from 14 middle/low- and high-resource countries. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURE: Ratings of categories of the ICF relevant
      for SCI were analyzed. RESULTS: Five models were tested on the complete sample
      and 5 subgroups. The overall reliability of all models and reliability within
      dimensions of the unidimensional and 2-dimensional models were good to excellent.
      The ICF categories spread well along the disability scale. The model fit
      improvement from the unidimensional to the 2-dimensional and from the 2
      dimensional to the 3-dimensional model was significant in all groups (P<.0001).
      The improvement, however, from a unidimensional to a 2-dimensional structure was
      markedly better than from a 2-dimensional to a 3-dimensional one. CONCLUSIONS: We
      propose that a 2-dimensional structure separating body functions and body
      structures from the activity and participation categories should serve as a basis
      for developing clinical measures in SCI in the future.

PMID- 25064777
TI  - Mirror therapy enhances motor performance in the paretic upper limb after stroke:
      a pilot randomized controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of mirror therapy (MT) combined with
      bilateral arm training and graded activities to improve motor performance in the
      paretic upper limb after stroke. DESIGN: Randomized, controlled, assessor-blinded
      study. SETTING: Inpatient stroke rehabilitation center of a tertiary care
      teaching hospital. PARTICIPANTS: Patients with first-time ischemic or hemorrhagic
      stroke (N=20), confined to the territory of the middle cerebral artery, occurring
      <6 months before the commencement of the study. INTERVENTION: The MT and control
      group participants underwent a patient-specific multidisciplinary rehabilitation
      program including conventional occupational therapy, physical therapy, and speech
      therapy for 5 d/wk, 6 h/d, over 3 weeks. The participants in the MT group
      received 1 hour of MT in addition to the conventional stroke rehabilitation. MAIN
      OUTCOME MEASURES: The Upper Extremity Fugl-Meyer Assessment for motor recovery,
      Brunnstrom stages of motor recovery for the arm and hand, Box and Block Test for
      gross manual hand dexterity, and modified Ashworth scale to assess the
      spasticity. RESULTS: After 3 weeks of MT, mean change scores were significantly
      greater in the MT group than in the control group for the Fugl-Meyer Assessment
      (P=.008), Brunnstrom stages of motor recovery for the arm (P=.003) and hand
      (P=.003), and the Box and Block Test (P=.022). No significant difference was
      found between the groups for modified Ashworth scale (P=.647). CONCLUSIONS: MT
      when combined with bilateral arm training and graded activities was effective in
      improving motor performance of the paretic upper limb after stroke compared with
      conventional therapy without MT.

PMID- 25064778
TI  - Outcome of percutaneous osseointegrated prostheses for patients with unilateral
      transfemoral amputation at two-year follow-up.
AB  - OBJECTIVE: To report outcomes regarding general and specific physical health
      related quality of life of treatment with percutaneous osseointegrated
      prostheses. DESIGN: Prospective 2-year case-control study. SETTING: University
      hospital. PARTICIPANTS: Individuals (N=39; mean age, 44 +/- 12.4 y) with
      unilateral transfemoral amputation as a result of trauma (n=23), tumor (n=11), or
      other cause (n=5). At baseline, 33 of the 39 participants used socket-suspended
      prostheses. INTERVENTION: Osseointegrated prosthesis. MAIN OUTCOME MEASURES:
      Questionnaire for Persons with Transfemoral Amputation (Q-TFA), Medical Outcomes
      Study 36-Item Short-Form Health Survey (SF-36) physical functioning (PF) and
      physical component summary (PCS), SF-6D, and Physiological Cost Index (PCI).
      RESULTS: At 2 years postimplantation, 6 of 7 Q-TFA scores improved (P<.0001)
      compared with baseline (prosthetic use, mobility, problem, global, capability,
      walking habits). The walking aid subscore did not improve (P=.327). Of the 39
      participants, increased prosthesis use was reported by 26, same amount of use by
      11, and less use by 2. Improvement was reported in 16 of the 30 separate problem
      items (P<.05). Unchanged items included problems regarding phantom limb pain and
      pain from the back, shoulders, and contralateral limb. The PF, PCS, and SF-6D
      improved a mean of 24.1 +/- 21.4 (P<.0001), 8.5 +/- 9.7 (P<.0001), and .039 +/-
      .11 (P=.007) points, respectively. Walking energy cost decreased (mean PCI at
      baseline, .749; mean PCI at follow-up, .61; P<.0001). CONCLUSIONS: Two years
      after intervention, patients with a unilateral TFA treated with an OPRA implant
      showed important improvements in prosthetic function and physical quality of
      life. However, walking aids used and the presence of phantom limb pain and pain
      in other extremities were unchanged. This information is valuable when
      considering whether percutaneous osseointegrated prostheses are a relevant
      treatment option.

PMID- 25064779
TI  - Reduction in energy expenditure during walking using an automated stride
      assistance device in healthy young adults.
AB  - OBJECTIVE: To investigate the effects of an automated stride assistance device
      that assists hip joint flexion and extension movement in energy expenditure
      during walking in healthy young adults using an expired gas method. DESIGN:
      Prospective, single-group design to compare the differences of energy expenditure
      between 2 assistive conditions. SETTING: Laboratory. PARTICIPANTS: Healthy
      volunteers (N=10) aged 21 to 32 years. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Oxygen consumption per unit time (Vo2) cost (ml.kg(-1).m(-1)),
      and heart rate (beats/min) were measured in 2 assistive conditions (with 3-Nm hip
      motion assistance and without assistance) and at 2 walking speeds (comfortable
      walking speed [CWS] and maximum walking speed [MWS]). RESULTS: There were no
      significant differences in walking speed between the with- and without-assistance
      conditions at either the CWS or MWS. The Vo2 cost and heart rate were
      significantly reduced in the with-assistance condition compared with the without
      assistance condition, at both the CWS and MWS. The reduction in the Vo2 cost
      during the with-assistance condition, relative to the without-assistance
      condition, was 7.06% at the CWS and 10.52% at the MWS. CONCLUSIONS: The automated
      stride assistance device is useful for reducing energy expenditure during walking
      in healthy adults. Further studies are warranted to investigate if this device
      provides substantial help to individuals with impaired mobility as a result of
      strength deficits.

PMID- 25064781
TI  - Effect of long-term physical activity and acute exercise on markers of systemic
      inflammation in persons with chronic spinal cord injury: a systematic review.
AB  - OBJECTIVE: To evaluate the effect of long-term physical activity (PA) and acute
      exercise on markers of systemic inflammation in persons with chronic spinal cord
      injury (SCI). DATA SOURCES: We searched PubMed (MEDLINE), EMBASE, Central
      Register of Controlled Trials, CINAHL, and PEDro, involving variations of the
      Medical Subject Headings: SCI, PA, exercise, and inflammation. No time or
      language restrictions were applied. STUDY SELECTION: Except for case reports, we
      included any type of study, both sexes, all ages, with SCI, resulting in the
      inclusion of 11 studies. PA included leisure or work activity, including
      exercise. DATA EXTRACTION: Two authors independently scanned titles and abstracts
      and read the articles included. One author extracted and the second double
      checked the data. The methodological quality and evidence were rated by using the
      Cochrane Risk of Bias tool or the Newcastle-Ottawa Scale and the Grading of
      Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS:
      The included studies had a high risk of bias and "very low" levels of evidence.
      Meta-analyses were performed (random-effects model or generic inverse variance
      method). The acute interleukin-6 (IL-6) response to exercise was the same for
      individuals with SCI and able-bodied individuals (P=.91); however, responses were
      higher in those with paraplegia than in those with tetraplegia (weighted mean
      difference, 1.19, P<.0001, and 0.25, P=.003, respectively). Compared with
      physically inactive people with SCI, physically active people with SCI had lower
      plasma C-reactive protein (CRP) levels (weighted mean difference, -0.38; P=.009).
      CRP concentrations were lower after the exercise intervention than before the
      exercise intervention (weighted mean difference, -2.76; P=.0001). CONCLUSIONS: PA
      and exercise may improve systemic markers of low-grade inflammation in those with
      SCI, particularly IL-6 and CRP. The change in IL-6 and CRP levels seems to be
      greater in those with paraplegia than in those with tetraplegia.

PMID- 25064780
TI  - Ultrasound elastography: the new frontier in direct measurement of muscle
      stiffness.
AB  - The use of brightness-mode ultrasound and Doppler ultrasound in physical medicine
      and rehabilitation has increased dramatically. The continuing evolution of
      ultrasound technology has also produced ultrasound elastography, a cutting-edge
      technology that can directly measure the mechanical properties of tissue,
      including muscle stiffness. Its real-time and direct measurements of muscle
      stiffness can aid the diagnosis and rehabilitation of acute musculoskeletal
      injuries and chronic myofascial pain. It can also help monitor outcomes of
      interventions affecting muscle in neuromuscular and musculoskeletal diseases, and
      it can better inform the functional prognosis. This technology has implications
      for even broader use of ultrasound in physical medicine and rehabilitation
      practice, but more knowledge about its uses and limitations is essential to its
      appropriate clinical implementation. In this review, we describe different
      ultrasound elastography techniques for studying muscle stiffness, including
      strain elastography, acoustic radiation force impulse imaging, and shear-wave
      elastography. We discuss the basic principles of these techniques, including the
      strengths and limitations of their measurement capabilities. We review the
      current muscle research, discuss physiatric clinical applications of these
      techniques, and note directions for future research. 

PMID- 25064782
TI  - Incidence of polymerase chain reaction-diagnosed Clostridium difficile in a large
      high-risk cohort, 2011-2012.
AB  - OBJECTIVE: To describe incidence rates (IRs) of polymerase chain reaction (PCR)
      diagnosed Clostridium difficile infection (CDI) in a large high-risk cohort.
      PATIENTS AND METHODS: Members of Kaiser Permanente Southern California 1 year or
      older who were admitted to any of 14 Kaiser Permanente hospitals from January 1,
      2011, through December 31, 2012, were included in the study. The CDI cases were
      identified by PCR in the inpatient and outpatient settings. The CDI IRs per
      10,000 inpatient-days are estimated by year, surveillance category, age, sex,
      race/ethnicity, and Charlson comorbidity index. Recurrence rates are presented by
      age, sex, and race/ethnicity. Death and colectomy in the 30 days after CDI
      diagnosis, white blood cell count, and serum creatinine level are assessed.
      RESULTS: Among 268,655 patients, 4286 (1.6%) had CDI. Among these patients, 671
      (15.7%) had recurrent infections. The IR was highest among community-onset,
      health care facility-associated infections (11.1 per 10,000 inpatient-days). The
      CDI IRs differed by age, sex, and race/ethnicity. Overall, 528 patients (12.3%)
      died within 30 days of a positive CDI test result. The CDI IRs increased 34% with
      implementation of PCR testing. CONCLUSION: Increasingly, PCR is being used
      because of its higher diagnostic sensitivity. Reassessing the epidemic using PCR
      updates our understanding of CDI risk. Our capacity to identify patients
      presenting in the outpatient setting after discharge provides a more accurate
      picture of health care-associated CDI rates, particularly because the community
      appears to assume an increasing role in CDI onset and possibly transmission. The
      CDI burden differs by race, comorbidity, sex, and previous health care use. The
      detected increase in CDI incidence after transitioning to PCR diagnosis was
      modest compared with previous studies.

PMID- 25064783
TI  - An evolutionarily conserved alternate metal ligand is important for activity in
      alpha-isopropylmalate synthase from Mycobacterium tuberculosis.
AB  - Members of the DRE-TIM metallolyase superfamily rely on an active-site divalent
      cation to catalyze various reactions involving the making and breaking of carbon
      carbon bonds. While the identity of the metal varies, the binding site is well
      conserved at the superfamily level with an aspartic acid and two histidine
      residues acting as ligands to the metal. Previous structural and bioinformatics
      results indicate that the metal can adopt an alternate architecture through the
      addition of an asparagine residue as a fourth ligand. This asparagine residue is
      strictly conserved in all members of the DRE-TIM metallolyase superfamily except
      fungal homocitrate synthase (HCS-lys) where it is replaced with isoleucine. The
      role of this additional metal ligand in alpha-isopropylmalate synthase from
      Mycobacterium tuberculosis (MtIPMS) has been investigated using site-directed
      mutagenesis. Substitution of the asparagine ligand with alanine or isoleucine
      results in inactive enzymes with respect to alpha-isopropylmalate formation.
      Control experiments suggest that the substitutions have not drastically affected
      the enzyme's structure indicating that the asparagine residue is essential for
      catalysis. Interestingly, all enzyme variants retained acetyl CoA hydrolysis
      activity in the absence of alpha-ketoisovalerate, similar to the wild-type
      enzyme. In contrast to the requirement of magnesium for alpha-isopropylmalate
      formation, hydrolytic activity could be inhibited by the addition of magnesium
      chloride in wild-type, D81E, and N321A MtIPMS, but not in the other variants
      studied. Attempts to rescue loss of activity in N321I MtIPMS by mimicking the
      fungal HCS active site through the D81E/N321I double variant were unsuccessful.
      This suggests epistatic constraints in evolution of function in IPMS and HCS-lys
      enzymes. 

PMID- 25064784
TI  - Non-fragile Hinfinity output feedback control design for continuous-time fuzzy
      systems.
AB  - In this paper, we investigate the problem of non-fragile Hinfinity fuzzy control
      design for continuous Takagi Sugeno (T-S) fuzzy systems with uncertainties,
      external disturbance and unmeasurable state variables. For the case of controller
      and observer gain additive variations, we propose a new solution of the fragility
      problem by developing the non-fragile design schemes ensuring the asymptotic
      stability and Hinfinity performance for the resulting closed loop systems. By
      considering a fuzzy Lyapunov function and by introducing slack variables, we
      propose the new sufficient stabilization conditions formulated in LMI constraints
      which can be easily solved using the convex optimization tools. The effectiveness
      the proposed results are illustrated through three numerical examples. 

PMID- 25064785
TI  - Updates for the International Standards for Neurological Classification of Spinal
      Cord Injury.
AB  - The International Standards for Neurological Classification of Spinal Cord Injury
      (ISNCSCI) is the most widely used classification in the field of spinal cord
      injury medicine. Since its first publication in 1982, multiple revisions refining
      the recommended examination, scaling, and classification have taken place to
      improve communication, consistency, and clarity. This article describes a brief
      historical perspective on the development and changes over the years leading to
      the current ISNCSCI, detailing the most recent updates of 2011 and the worksheet
      2013 as well as issues facing the ISNCSCI for the future. 

PMID- 25064786
TI  - Hypothermia as a clinical neuroprotectant.
AB  - Applying therapeutic hypothermia (TH) for the purposes of neuroprotection,
      originally termed "hibernation," started nearly 100 years ago. Because TH cooling
      systems have improved to the point where it is practical and safe for general
      application, interest in providing such treatment in conditions such as spinal
      cord injury, traumatic brain injury, stroke, and cardiac arrest has increased.
      This article reviews the mechanisms by which TH mitigates secondary neurologic
      injury, the clinical scenarios where TH is being applied, and reviews selected
      published studies using TH for central nervous system neuroprotection. 

PMID- 25064787
TI  - Assessment of neuromuscular conditions using ultrasound.
AB  - Upper extremity pain in persons with spinal cord injury is a common cause of
      morbidity. Ultrasound of nerve, muscle, and tendon has the potential to become a
      valuable modality in assessing this population, and has the advantage of reduced
      health care costs, portability, and use in populations that cannot tolerate MRI.
      It has the potential to detect issues before the onset of significant morbidity,
      and preserve patient independence. Upper extremity ultrasound already has many
      studies showing its utility in diagnosis, and newer techniques have the potential
      to enhance its use in the diagnosis and management of musculoskeletal conditions.

PMID- 25064788
TI  - Chronic neuropathic pain in SCI: evaluation and treatment.
AB  - Chronic neuropathic pain develops in approximately 40% of people after a spinal
      cord injury (SCI) and is notoriously difficult to treat. Because of the frequent
      presence of more than one pain type and the complex mechanisms and symptoms
      associated with pain in individuals with SCI, a thorough evaluation is important.
      This review includes an overview of the most recent guidelines for evaluating and
      classifying pain, suggestions for standardizing outcome measures for clinical
      use, and a review of the positive and negative evidence for pharmacologic and
      nonpharmacologic interventions to consider when treating individuals with SCI and
      chronic neuropathic pain. 

PMID- 25064789
TI  - Reducing cardiometabolic disease in spinal cord injury.
AB  - Accelerated cardiometabolic disease is a serious health hazard after spinal cord
      injuries (SCI). Lifestyle intervention with diet and exercise remains the
      cornerstone of effective cardiometabolic syndrome treatment. Behavioral
      approaches enhance compliance and benefits derived from both diet and exercise
      interventions and are necessary to assure that persons with SCI profit from
      intervention. Multitherapy strategies will likely be needed to control
      challenging component risks, such as gain in body mass, which has far reaching
      implications for maintenance of daily function as well as health. 

PMID- 25064790
TI  - Strategies for prevention of urinary tract infections in neurogenic bladder
      dysfunction.
AB  - In this article, the problem of urinary tract infections (UTIs) after spinal cord
      injury and disorders is defined, the relationship of bladder management to UTIs
      is discussed, and mechanical and medical strategies for UTI prevention in spinal
      cord injury and disorders are described. 

PMID- 25064791
TI  - Diaphragmatic pacing in spinal cord injury.
AB  - After cervical spinal cord injuries, many patients are unable to sustain
      independent ventilation because of a disruption of diaphragm innervation and
      respiratory functioning. If phrenic nerve function is preserved, the patient may
      be able to tolerate exogenous pacing of the diaphragm via electrical stimulation.
      Previously this was accomplished by stimulation directly to the phrenic nerves,
      but may be accomplished less invasively by percutaneously stimulating the
      diaphragm itself. The benefits, when compared with mechanical ventilation,
      include a lower rate of pulmonary complications, improved venous return, more
      normal breathing and speech, facilitation of eating, cost-effectiveness, and
      increased patient mobility. 

PMID- 25064793
TI  - Spasticity and the use of intrathecal baclofen in patients with spinal cord
      injury.
AB  - Muscle spasms and spasticity constitute a significant problem in patients with
      spinal cord injury, interfering with rehabilitation and leading to impairments in
      quality of life in addition to medical complications. Administration of
      intrathecal baclofen (ITB) is indicated when spasticity continues to produce a
      clinical disability despite trials of oral treatments and other alternatives in
      patients who have functional goals and/or pain without contractures. Severe
      spasticity of spinal origin has been shown to respond dramatically to long-term
      ITB when used in appropriate patients with spasticity. 

PMID- 25064794
TI  - Spinal cord injury pressure ulcer treatment: an experience-based approach.
AB  - Pressure ulcers continue to impact the lives of spinal cord injury patients
      severely. Pressure ulcers must be accurately staged according to National
      Pressure Ulcer Advisory recommendations before treatment design. The first
      priority in treatment of pressure ulcers is offloading. Intact skin ulcers may be
      treated with noncontact nonthermal low-frequency ultrasound. Superficial pressure
      ulcers may be treated with a combination of collagenase and foam dressings.
      Deeper pressure ulcers warrant negative-pressure wound therapy dressings along
      with biologic adjuncts to fill in wound depth. Discovery and treatment of
      osteomyelitis is a high priority when initially evaluating pressure ulcers.
      Surgical intervention must always be considered. 

PMID- 25064795
TI  - Dual diagnosis: traumatic brain injury with spinal cord injury.
AB  - Spinal cord injury (SCI) patients should be assessed for a co-occurring traumatic
      brain injury (TBI) on admission to a rehabilitation program. Incidence of a dual
      diagnosis may approach 60% with certain risk factors. Diagnosis of mild-moderate
      severity TBIs may be missed during acute care hospitalizations of SCI.
      Neuropsychological symptoms of a missed TBI diagnosis may be perceived during
      rehabilitation as noncompliance, inability to learn, maladaptive reactions to
      SCI, and poor motivation. There are life-threatening and quality-of-life
      threatening complications of TBI that also may be missed if a dual diagnosis is
      not made. 

PMID- 25064792
TI  - Functional electrical stimulation and spinal cord injury.
AB  - Spinal cord injuries (SCI) can disrupt communications between the brain and the
      body, resulting in loss of control over otherwise intact neuromuscular systems.
      Functional electrical stimulation (FES) of the central and peripheral nervous
      system can use these intact neuromuscular systems to provide therapeutic exercise
      options to allow functional restoration and to manage medical complications
      following SCI. The use of FES for the restoration of muscular and organ functions
      may significantly decrease the morbidity and mortality following SCI. Many FES
      devices are commercially available and should be considered as part of the
      lifelong rehabilitation care plan for all eligible persons with SCI. 

PMID- 25064796
TI  - Spinal cord injury rehabilitation.

PMID- 25064797
TI  - Spinal cord injury rehabilitation.

PMID- 25064798
TI  - Evaluating the impact of climate change on groundwater resources in a small
      Mediterranean watershed.
AB  - Western Mediterranean Region of Turkey is subject to considerable impacts of
      climate change that may adversely affect the water resources. Decrease in annual
      precipitation and winter precipitation as well as increase in temperatures are
      observed since 1960s. In this study, the impact of climate change on groundwater
      resources in part of Koycegiz-Dalyan Watershed was evaluated. Evaluation was done
      by quantifying the impacts of climate change on the water budget components.
      Hydrological modeling was conducted with SWAT model which was calibrated and
      validated successfully. Climate change and land use scenarios were used to
      calculate the present and future climate change impacts on water budgets.
      According to the simulation results, almost all water budget components have
      decreased. SWAT was able to allocate less irrigation water because of the
      decrease of overall water due to the climate change. This resulted in an increase
      of water stressed days and temperature stressed days whereas crop yields have
      decreased according to the simulation results. The results indicated that lack of
      water is expected to be a problem in the future. In this manner, investigations
      on switching to more efficient irrigation methods and to crops with less water
      consumption are recommended as adaptation measures to climate change impacts. 

PMID- 25064799
TI  - A novel missense mutation in HSD17B3 gene in a 46, XY adolescent presenting with
      primary amenorrhea and virilization at puberty.
AB  - Deficiency of 17beta-hydroxysteroid dehydrogenase type3 (17beta-HSD3) isoenzyme
      which catalyzes the synthesis of testosterone from Delta4-androstenedione, is the
      cause of 46, XY disorders of sex development (DSD). 17beta-HSD3 deficiency is a
      rare autosomal recessive disorder, which is caused by mutations in the HSD17B
      gene found on chromosome 9q22. Up to now, almost 33 mutations in the HSD17B3 gene
      have been reported. Here, we report a patient with a novel mutation in HSD17B3
      gene leading to 17beta-HSD3 deficiency. The patient was admitted because of
      primary amenorrhea and signs of virilization at puberty. The chromosome analysis
      showed a 46, XY karyotype. Hormonal evaluation revealed a high Delta4
      androstenedione level with a low serum testosterone/androstenedione (T/A) ratio.
      Sequence analysis of HSD17B3 gene revealed the presence of a homozygous missense
      mutation in exon 11 resulting in a premature stop codon (p.Y287). Gonadectomy was
      performed after the molecular diagnosis and estrogen replacement therapy was
      initiated. With this report, we emphasize that 17beta-HSD3 deficiency should be
      considered in virilized female patients at puberty if the T/A ratio is less than
      0.8, and the molecular analysis should be performed for the precise diagnosis and
      genetic counseling. 

PMID- 25064800
TI  - Matrix metalloproteinases and left ventricular function and structure in spinal
      cord injured subjects.
AB  - Subjects with spinal cord injury (SCI) exhibit impaired left ventricular (LV)
      diastolic function, which has been reported to be attenuated by regular physical
      activity. This study investigated the relationship between circulating matrix
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) and
      echocardiographic parameters in SCI subjects and the role of physical activity in
      this regard. Forty-two men with SCI [19 sedentary (S-SCI) and 23 physically
      active (PA-SCI)] were evaluated by clinical, anthropometric, laboratory, and
      echocardiographic analysis. Plasmatic pro-MMP-2, MMP-2, MMP-8, pro-MMP-9, MMP-9,
      TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay and
      zymography. PA-SCI subjects presented lower pro-MMP-2 and pro-MMP-2/TIMP-2 levels
      and improved markers of LV diastolic function (lower E/Em and higher Em and E/A
      values) than S-SCI ones. Bivariate analysis showed that pro-MMP-2 correlated
      inversely with Em and directly with E/Em, while MMP-9 correlated directly with LV
      mass index and LV end-diastolic diameter in the whole sample. Following multiple
      regression analysis, pro-MMP-2, but not physical activity, remained associated
      with Em, while MMP-9 was associated with LV mass index in the whole sample. These
      findings suggest differing roles for MMPs in LV structure and function regulation
      and an interaction among pro-MMP-2, diastolic function and physical activity in
      SCI subjects. 

PMID- 25064801
TI  - Association between parent and child distress and the moderating effects of life
      events in families with and without a history of pediatric cancer.
AB  - OBJECTIVE: Examined the associations between parental and child distress, and
      moderating effects of child exposure to life events, in families with and without
      a history of pediatric cancer.  METHODS: Children with cancer and their parents
      (N = 255) and healthy comparison dyads (N = 142) completed self-report measures
      of depression, anxiety, and posttraumatic stress symptoms. Children reported on
      the total number of stressful life events they had experienced. Correlations
      between parental and child symptoms were examined. Moderating effects of child
      exposure to life events were tested using multiple regression.  RESULTS: Parent
      and child symptoms were significantly related only in the cancer group. Child
      exposure to life events attenuated this relationship. Moderation effects were
      significant at or below average levels of life stress.  CONCLUSIONS: The
      experience of childhood cancer may strengthen the link between parent and child
      psychological functioning. However, child exposure to other life events may
      weaken this link.

PMID- 25064802
TI  - Individual differences and day-to-day fluctuations in perceived self-regulation
      associated with daily adherence in late adolescents with type 1 diabetes.
AB  - OBJECTIVE: To examine whether individual differences and intraindividual (within
      person day-to-day) fluctuations in late adolescents' self-regulation were
      associated with daily adherence to the type 1 diabetes regimen.  METHODS:  110
      school seniors (M age = 17.78 years) and their mothers assessed adolescents'
      skills underlying self-regulation (executive function, attention, self-control,
      behavioral inhibition and activation, emotion regulation) and adherence, with
      glycosylated hemoglobin from medical records. Teens completed daily diaries
      reporting self-regulation failures surrounding monitoring blood glucose,
      adherence, and number of blood glucose checks each day for 14 days.  RESULTS: 
      Hierarchical Linear Models indicated that better daily adherence was associated
      with teen and mother reports of better self-regulation skills and teens' reports
      of fewer daily self-regulation failures. Daily adherence was unrelated to
      temperamental differences in behavioral inhibition and activation.  CONCLUSIONS: 
      Results indicate that both individual and intraindividual differences in self
      regulation contribute to daily adherence highlighting the importance of daily
      self-regulatory challenges to adherence.

PMID- 25064803
TI  - A bioengineered peripheral nerve construct using aligned peptide amphiphile
      nanofibers.
AB  - Peripheral nerve injuries can result in lifelong disability. Primary coaptation
      is the treatment of choice when the gap between transected nerve ends is short.
      Long nerve gaps seen in more complex injuries often require autologous nerve
      grafts or nerve conduits implemented into the repair. Nerve grafts, however,
      cause morbidity and functional loss at donor sites, which are limited in number.
      Nerve conduits, in turn, lack an internal scaffold to support and guide axonal
      regeneration, resulting in decreased efficacy over longer nerve gap lengths. By
      comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into
      nanofibers, which can be aligned to mimic the native architecture of peripheral
      nerve. As such, they represent a potential substrate for use in a bioengineered
      nerve graft substitute. To examine this, we cultured Schwann cells with bioactive
      PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate
      within the biomaterial. Next, we devised a PA construct for use in a peripheral
      nerve critical sized defect model. Rat sciatic nerve defects were created and
      reconstructed with autologous nerve, PLGA conduits filled with various forms of
      aligned PAs, or left unrepaired. Motor and sensory recovery were determined and
      compared among groups. Our results demonstrate that Schwann cells are able to
      adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive
      PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor
      and sensory function in animals treated with conduit/PA constructs comparable to
      animals treated with autologous nerve grafts. Functional recovery in conduit/PA
      and autologous graft groups was significantly faster than in animals treated with
      empty PLGA conduits. Histological examinations also demonstrated increased axonal
      and Schwann cell regeneration within the reconstructed nerve gap in animals
      treated with conduit/PA constructs. These results indicate that PA nanofibers may
      represent a promising biomaterial for use in bioengineered peripheral nerve
      repair. 

PMID- 25064804
TI  - Poly(lactic-co-glycolic) acid microspheres encapsulated in Pluronic F-127 prolong
      hirudin delivery and improve functional recovery from a demyelination lesion.
AB  - Components of the blood have been proposed as potential therapeutic targets for
      improving cellular regeneration after injury and neurodegenerative disease. In
      this work, thrombin is shown to increase endogenous neural progenitor
      proliferation in the intact murine spinal cord. A local injection of heparin
      before a spinal cord injury reduces cell proliferation and astrogliogenesis
      associated with scarring. We sought to create depot-formulations of PLGA
      microsphere and Pluronic F-127 for sustained local delivery of two thrombin
      inhibitors, heparin and hirudin. Each hydrogel depot-formulation showed delayed
      drug release compared to microspheres or hydrogel alone. Animals with a lateral
      demyelination lesion showed a reduction in CD68+ macrophages when treated with
      hirudin-loaded PLGA/F-127 gels compared to control and heparin-treated animals.
      Moreover, hirudin-loaded materials showed an accelerated recovery in coordinated
      stepping and increased oligodendrocyte densities. Together, these data
      demonstrate that controlled delivery of hirudin accelerates functional recovery
      from a demyelination lesion in the spinal cord. 

PMID- 25064805
TI  - Cytotoxicity and therapeutic effect of irinotecan combined with selenium
      nanoparticles.
AB  - Although chemotherapeutic drugs are widely applied for clinic tumor treatment,
      severe toxicity restricts their therapeutic efficacy. In this study, we reported
      a new form of selenium, selenium nanoparticles (Nano Se) which have significant
      lower toxicity and acceptable bioavailability. We investigated Nano Se as
      chemotherapy preventive agent to protect against toxicities of anticancer drug
      irinotecan and synergistically enhance the anti-tumor treatment effect in vitro
      and in vivo. The underlying mechanisms were also investigated. The combination of
      Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells
      likely by p53 mediated apoptosis. Nano Se inhibited growth of HCT-8 tumor cells
      partially through caspases mediated apoptosis. In vivo experiment showed Nano Se
      at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by
      irinotecan (60 mg/kg) treatment. Nano Se alone treatment did not induce any toxic
      manifestations. The combination of Nano Se and irinotecan dramatically inhibited
      tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells
      xenografted tumor. Tumor inhibition rate was about 17.2%, 48.6% and 62.1% for
      Nano Se, irinotecan and the combination of Nano Se and irinotecan, respectively.
      The beneficial effects of Nano Se for tumor therapy were mainly ascribed to
      selectively regulating Nrf2-ARE (antioxidant responsive elements) pathway in
      tumor tissues and normal tissues. Our results suggest Nano Se is a promising
      selenium species with potential application in cancer treatment. 

PMID- 25064806
TI  - A phenotypic culture system for the molecular analysis of CNS myelination in the
      spinal cord.
AB  - Studies of central nervous system myelination lack defined in vitro models which
      would effectively dissect molecular mechanisms of myelination that contain cells
      of the correct phenotype. Here we describe a co-culture of purified motoneurons
      and oligodendrocyte progenitor cells, isolated from rat embryonic spinal cord
      using a combination of immunopanning techniques. This model illustrates
      differentiation of oligodendrocyte progenitors into fully functional mature
      oligodendrocytes that myelinate axons. It also illustrates a contribution of
      axons to the rate of oligodendrocyte maturation and myelin gene expression. The
      defined conditions used allow molecular analysis of distinct stages of
      myelination and precise manipulation of inductive cues affecting axonal
      oligodendrocyte interactions. This phenotypic in vitro myelination model can
      provide valuable insight into our understanding of demyelinating disorders, such
      as multiple sclerosis and traumatic diseases such as spinal cord injury where
      demyelination represents a contributing factor to the pathology of the disorder. 

PMID- 25064807
TI  - Different biogenetic causal explanations and attitudes towards persons with major
      depression, schizophrenia and alcohol dependence: is the concept of a chemical
      imbalance beneficial?
AB  - OBJECTIVE: It is unclear whether different biogenetic causal beliefs affect
      stigmatization of mentally-ill patients differently. It has been argued that in
      particular believing in a 'chemical imbalance' as a cause of mental disorder
      might be associated with more tolerant attitudes. METHOD: In a representative
      population survey in Germany (n=3642), using unlabelled case vignettes of persons
      with depression, schizophrenia, or alcohol dependence, we elicited agreement with
      three different biogenetic explanations of the illness: 'Chemical imbalance of
      the brain', 'brain disease' and 'heredity'. We further investigated emotional
      reactions as well as the desire for social distance. For each vignette condition
      we calculated linear regressions with each biogenetic explanation as independent
      and emotional reactions as well as social distance as dependent variable
      controlling for socio-demographic variables. LIMITATIONS: Our cross-sectional
      study does not allow statements regarding causality and the explanatory power of
      our statistical models was low. RESULTS: 'Chemical imbalance of the brain' and
      'brain disease' were both associated with a stronger desire for social distance
      in schizophrenia and depression, and with more social acceptance in alcohol
      dependence, whereas 'heredity' was not significantly associated with social
      distance in any of the investigated illnesses. All three biogenetic causal
      beliefs were associated with more fear in all three illnesses. CONCLUSION: Our
      study corroborates findings that biogenetic explanations have different effects
      in different disorders, and seem to be harmful in depression and schizophrenia. A
      particular de-stigmatizing potential of the causal belief 'chemical imbalance'
      could not be found. Implications for useful anti-stigma messages are discussed.

PMID- 25064808
TI  - Possible involvement of rumination in gray matter abnormalities in persistent
      symptoms of major depression: an exploratory magnetic resonance imaging voxel
      based morphometry study.
AB  - BACKGROUND: A recent meta-analysis of many magnetic resonance imaging (MRI)
      studies has identified brain regions with gray matter (GM) abnormalities in
      patients with major depressive disorder (MDD). A few studies addressing GM
      abnormalities in patients with treatment-resistant depression (TRD) have yielded
      inconsistent results. Moreover, although TRD patients tend to exhibit ruminative
      thoughts, it remains unclear whether rumination is related to GM abnormalities in
      such patients or not. METHODS: We conducted structural MRI scans and voxel-based
      morphometry (VBM) to identify GM differences among 29 TRD patients and 29 healthy
      age-matched and sex-matched controls. A response style questionnaire was used to
      assess the respective degrees of rumination in TRD patients. Structural
      correlates of rumination were examined. RESULTS: TRD patients showed several
      regions with smaller GM volume than in healthy subjects: the left dorsal anterior
      cingulate cortex (ACC), right ventral ACC, right superior frontal gyrus, right
      cerebellum (Crus I), and cerebellar vermis. GM volumes in these regions did not
      correlate to rumination. However, whole-brain analysis revealed that rumination
      was positively correlated with the GM volume in the right superior temporal gyrus
      in TRD patients. LIMITATIONS: Structural correlates of rumination were examined
      only in TRD patients. CONCLUSIONS: Our data provide additional evidence
      supporting the hypothesis that TRD patients show GM abnormalities compared with
      healthy subjects. Furthermore, this report is the first to describe a study
      identifying brain regions for which the GM volume is correlated with rumination
      in TRD patients. These results improve our understanding of the anatomical
      characteristics of TRD.

PMID- 25064809
TI  - Beliefs of people taking antidepressants about causes of depression and reasons
      for increased prescribing rates.
AB  - BACKGROUND: Public beliefs about the causes of mental health problems are related
      to desire for distance and pessimism about recovery, and are therefore frequently
      studied. The beliefs of people receiving treatment are researched less often.
      METHOD: An online survey on causal beliefs about depression and experiences with
      antidepressants was completed by 1829 New Zealand adults prescribed anti
      depressants in the preceding five years, 97.4% of whom proceeded to take
      antidepressants. RESULTS: The most frequently endorsed of 17 causal beliefs were
      family stress, relationship problems, loss of loved one, financial problems,
      isolation, and abuse or neglect in childhood. Factor analysis produced three
      factors: 'bio-genetic', 'adulthood stress' and 'childhood adversity'. The most
      strongly endorsed explanations for increases in antidepressant prescribing
      invoked improved identification, reduced stigma and drug company marketing. The
      least strongly endorsed was 'Anti-depressants are the best treatment'. Regression
      analyses revealed that self-reported efficacy of the antidepressants was
      positively associated with bio-genetic causal beliefs, negatively associated with
      childhood adversity beliefs and unrelated to adulthood stress beliefs. The belief
      that 'People cannot' get better by themselves even if they try' was positively
      associated with bio-genetic beliefs. LIMITATIONS: The convenience sample may have
      been biased towards a favourable view of bio-genetic explanations, since 83%
      reported that the medication reduced their depression. CONCLUSIONS: Clinicians'
      should consider exploring patients' causal beliefs. The public, even when taking
      antidepressants, continues to hold a multi-factorial causal model of depression
      with a primary emphasis on psycho-social causes. A three factor model of those
      beliefs may lead to more sophisticated understandings of relationships with
      stigma variables.

PMID- 25064811
TI  - A multi-approach study of influence of growth temperature and nutrient
      deprivation in a strain of Aeromonas hydrophila.
AB  - In the present study we investigated the behavior of an Aeromonas hydrophila
      strain in prolonged nutrient deprivation condition analyzing the possible link
      among survival, cell morphology and adhesive characteristics and correlating them
      with the expression of the 43kDa outer membrane protein (OMP). The strain was
      inoculated in mineral and drinking chlorinated water, and in Nutrient Broth as a
      control with incubation at 4 and 24 degrees C for 176days. Specimens were
      analyzed at different times during starvation stress. Viability was assessed by
      flow cytometry and growth by plate count technique; morphology and adhesivity
      were detected by optical and electron microscopy. The 43kDa OMP expression at
      different times was determined after immunoblotting assay using a polyclonal
      antibody produced in rabbit. The results showed a long-term viability as
      evidenced by cytofluorimetric analysis; however, the prolonged starvation led to
      the shift from the normal rod shaped cells to spherical forms in the last phases
      of incubation especially at 24 degrees C. Concomitantly with the appearance of
      spherical cells we noted a reduction of the 43kDa OMP content and adhesive
      ability. Therefore, our results suggest a role of the 43kDa OMP as adhesin in A.
      hydrophila. In conclusion, we demonstrated that the bacterium can long survive
      under stress conditions, however adopting strategies which can lead to a loss of
      some cell surface components involved in the interactions with eukaryotic cells,
      therefore modifying its virulence properties. 

PMID- 25064810
TI  - The chronic impact of work on suicides and under-utilization of psychiatric and
      psychosocial services.
AB  - BACKGROUND: Work-related stress appears to be a contributing factor in the lives
      of employed people who kill themselves, particularly during economic downturns.
      However, few studies have compared them with working community controls who may
      be experiencing similar strains, in order to explore the role of mental disorders
      in these deaths and the implication of such strains on their service use pattern.
      We hypothesized that both work stress and mental illness were associated with
      suicides, and that mental illness served as the mediator between work stress and
      suicide. Based on the Behavioral Model, we also assumed work stress associated
      with their use of services. METHODS: A sample of 175 employed individuals
      (suicides=63; controls=112) drawn from a psychological autopsy (PA) dataset was
      examined based on demographics and socioeconomic factors, psychiatric diagnoses
      and use of services, psychosocial factors, and life events. A mediator analysis
      was conducted to examine the impact of work on suicides. RESULTS: Suicides
      generally had depression and anxiety, debts, higher impulsivity and poorer social
      support in comparison to controls. Chronic impact from work, which was fully
      mediated by psychiatric illness, was found higher among those suicides that did
      not seek contact with clinical service providers. LIMITATIONS: PA is a post-hoc
      cross-sectional comparison method which does not allow causal analyses.
      CONCLUSION: It is important to develop new approaches for engaging vulnerable
      individuals in the workplace before they become suicidal, as their depression and
      social isolation can serve to cut them off from help when they are most in need.
      Occupational mental health programs should be made available for employees and
      their families.

PMID- 25064812
TI  - Prevalence and antimicrobial susceptibility of Arcobacter species in cow milk,
      water buffalo milk and fresh village cheese.
AB  - In this study, the presence of Arcobacter spp. was examined in cow milk (n=50),
      water buffalo (WB) milk (n=50) and fresh village cheese (n=50) samples. The 16S
      rDNA-RFLP method was used for the identification of Arcobacter spp. The disc
      diffusion method was used to investigate the susceptibility of all strains
      identified to 18 different antimicrobial substances. The most commonly isolated
      Arcobacter species were found to be Arcobacter butzleri (38.89%), Arcobacter
      cryaerophilus (22.23%) and Arcobacter skirrowii (11.12%) in cow milk; A.
      cryaerophilus (33.33%), Arcobacter cibarius (20.83%) and A. butzleri (12.50%) in
      WB milk; and A. skirrowii (28.57%), A. butzleri (21.43%) and A. cryaerophilus
      (14.29%) in fresh village cheese. This is the first study to identify the
      presence of Arcobacter nitrofigilis, Arcobacter cloacae, Arcobacter halophilus,
      Arcobacter bivalviorum and A. cibarius species in analyzed samples. It was found
      that all of the A. cryaerophilus (n:16) isolates were resistant to cefoperazone,
      cloxacillin and penicillin G; all of the A. skirrowii (n:12) and A. butzleri
      (n:10) isolates were resistant to cefoperazone, tetracycline, ampicillin,
      erythromycin, cloxacillin and penicillin G. It was concluded that cow milk, WB
      milk and fresh village cheese samples are an important source of Arcobacter
      species and pose a risk to public health. 

PMID- 25064813
TI  - Cloning, constitutive activity and expression profiling of two receptors related
      to relaxin receptors in Drosophila melanogaster.
AB  - Leucine-rich repeat containing G protein-coupled receptors (LGRs) comprise a
      cluster of transmembrane proteins, characterized by the presence of a large N
      terminal extracellular domain. This receptor group can be classified into three
      subtypes. Belonging to the subtype C LGRs are the mammalian relaxin receptors
      LGR7 (RXFP1) and LGR8 (RXFP2), which mediate important reproductive and other
      processes. We identified two related receptors in the genome of the fruit fly and
      cloned their open reading frames into an expression vector. Interestingly, dLGR3
      demonstrated constitutive activity at very low doses of transfected plasmid,
      whereas dLGR4 did not show any basal activity. Both receptors exhibited a similar
      expression pattern during development, with relatively high transcript levels
      during the first larval stage. In addition, both receptors displayed higher
      expression in male adult flies as compared to female flies. Analysis of the
      tissue distribution of both receptor transcripts revealed a high expression of
      dLGR3 in the female fat body, while the expression of dLGR4 peaked in the midgut
      of both the wandering and adult stage. 

PMID- 25064815
TI  - Orexin A enhances food intake in bullfrog larvae.
AB  - Orexin is a potent orexigenic peptide implicated in appetite regulation in
      rodents. However, except for teleost fish, the involvement of orexin in the
      regulation of feeding in non-mammalian vertebrates has not been well studied.
      Anuran amphibian larvae feed and grow during the pre- and prometamorphic stages.
      Therefore, orexigenic factors seem to play important roles in growing larvae.
      Indeed, our recent studies have demonstrated that neuropeptide Y and ghrelin
      exert orexigenic actions in bullfrog larvae during the prometamorphic stages. In
      this study, we examined the effect of intracerebroventricular (ICV)
      administration of synthetic orexin A on food intake in bullfrog larvae at the
      prometamorphic stages. Food intake was significantly increased by ICV
      administration of orexin A (at 6 pmol/g BW) during a 15-min observation period.
      The orexigenic action of orexin A at 6 pmol/g BW was blocked by treatment with an
      orexin receptor antagonist, SB334867, at 60 pmol/g BW. These results indicate
      that orexin A acts as an orexigenic factor in bullfrog larvae.

PMID- 25064814
TI  - Aedes cadherin mediates the in vivo toxicity of the Cry11Aa toxin to Aedes
      aegypti.
AB  - Cadherin plays an important role in the toxicity of Bacillus thuringiensis Cry
      proteins. We previously cloned a full-length cadherin from Aedes aegypti larvae
      and reported this protein binds Cry11Aa toxin from B. thuringiensis subsp.
      israelensis with high affinity, ~16.7nM. Based on these results, we investigated
      if Aedes cadherin is involved in the in vivo toxicity of Cry11Aa toxin to Ae.
      aegypti. We established a mosquito cell line stably expressing the full-length
      Aedes cadherin and transgenic mosquitoes with silenced Aedes cadherin expression.
      Cells expressing the Aedes cadherin showed increased sensitivity to Cry11Aa
      toxin. Cry11Aa toxin at 400nM killed approximately 37% of the cells in 3h.
      Otherwise, transgenic mosquitoes with silenced Aedes cadherin expression showed
      increased tolerance to Cry11Aa toxin. Furthermore, cells expressing Aedes
      cadherin triggered Cry11Aa oligomerization. These results show the Aedes cadherin
      plays a pivotal role in Cry11Aa toxicity to Ae. aegypti larvae by mediating
      Cry11Aa oligomerization. However, since high toxicity was not obtained in
      cadherin-expressing cells, an additional receptor may be needed for manifestation
      of full toxicity. Moreover, cells expressing Aedes cadherin were sensitive to
      Cry4Aa and Cry11Ba, but not Cry4Ba. However transgenic mosquitoes with silenced
      Aedes cadherin expression showed no tolerance to Cry4Aa, Cry4Ba, and Cry11Ba
      toxins. These results suggest that while Aedes cadherin may mediate Cry4Aa and
      Cry11Ba toxicity, this cadherin but is not the main receptor of Cry4Aa, Cry4Ba
      and Cry11Ba toxin in Ae. aegypti. 

PMID- 25064816
TI  - Direct and crossed effects of somatosensory stimulation on neuronal excitability
      and motor performance in humans.
AB  - This analytic review reports how prolonged periods of somatosensory electric
      stimulation (SES) with repetitive transcutaneous nerve stimulation can have
      'direct' and 'crossed' effects on brain activation, corticospinal excitability,
      and motor performance. A review of 26 studies involving 315 healthy and 78 stroke
      and dystonia patients showed that the direct effects of SES increased
      corticospinal excitability up to 40% (effect size: 0.2 to 6.1) and motor
      performance up to 14% (effect size: 0.3 to 3.1) but these two features did not
      correlate. SES did not affect measures of intracortical excitability. Most
      likely, a long-term potentiation-like mechanism in the excitatory glutamatergic
      connections between the primary sensory and motor cortices mediates the direct
      effects of SES on corticospinal excitability and motor performance. We propose
      two models for the untested hypothesis that adding SES to unilateral motor
      practice could magnify the magnitude of inter-limb transfer. If tenable, the
      hypothesis would expand the evolving repertoire of sensory augmentation of cross
      education using mirrors and add SES as an alternative to conventional
      rehabilitation strategies such as constraint-induced movement therapy. 

PMID- 25064817
TI  - Whole tobacco smoke extracts to model tobacco dependence in animals.
AB  - Smoking tobacco is highly addictive and a leading preventable cause of death. The
      main addictive constituent is nicotine; consequently it has been administered to
      laboratory animals to model tobacco dependence. Despite extensive use, this model
      might not best reflect the powerful nature of tobacco dependence because nicotine
      is a weak reinforcer, the pharmacology of smoke is complex and non
      pharmacological factors have a critical role. These limitations have led
      researchers to expose animals to smoke via the inhalative route, or to administer
      aqueous smoke extracts to produce more representative models. The aim was to
      review the findings from molecular/behavioural studies comparing the effects of
      nicotine to tobacco/smoke extracts to determine whether the extracts produce a
      distinct model. Indeed, nicotine and tobacco extracts yielded differential
      effects, supporting the initiative to use extracts as a complement to nicotine.
      Of the behavioural tests, intravenous self-administration experiments most
      clearly revealed behavioural differences between nicotine and extracts. Thus,
      future applications for use of this behavioural model were proposed that could
      offer new insights into tobacco dependence. 

PMID- 25064818
TI  - In vivo imaging and detection of nitroreductase in zebrafish by a new near
      infrared fluorescence off-on probe.
AB  - A new near-infrared fluorescence off-on probe is developed and applied to
      fluorescence imaging of nitroreductase in zebrafish in vivo. The probe is readily
      prepared by connecting 4-nitrobenzene as a quenching and recognizing moiety to a
      stable hemicyanine skeleton that can be formed via the decomposition of IR 780.
      The fluorescence off-on response of the probe to nitroreductase is based on the
      enzyme-catalyzed reduction of the 4-nitrobenzene moiety, followed by the 1,6
      rearrangement-elimination and the fluorophore release. Compared with the existing
      nitroreductase probes, the proposed probe exhibits superior analytical
      performance such as near-infrared fluorescence emission over 700 nm as well as
      high selectivity and sensitivity, with a detection limit of 14 ng/mL. More
      importantly, the probe has been successfully applied to visualize the
      distribution of nitroreductase in living zebrafish in vivo, revealing that
      nitroreductase might mainly exist in zebrafish yolk sac. The superior properties
      of the probe make it of great potential use in other biosystems and in vivo
      studies.

PMID- 25064819
TI  - Tethered-bead, immune sandwich assay.
AB  - We describe a proof-of-principle, immune sandwich assay in which immune complexes
      link micron-size beads via DNA tethers to a sensor surface. The number of
      tethered beads, counted using low-magnification microscopy, provides a measure of
      the concentration of analyte. The prototype assay was sensitive to pM
      concentration of analyte. In theory, the assay could be sensitive to sub-fM
      analyte because beads attached via single-immune complexes and DNA strands form
      tethers, and tether formation in the absence of analyte is extremely rare. The
      limiting step at present is binding of streptavidin at the end of DNA to biotin
      on capture beads. Potential advantages of this type of sensor are discussed. 

PMID- 25064820
TI  - Electrochemical cortisol immunosensors based on sonochemically synthesized zinc
      oxide 1D nanorods and 2D nanoflakes.
AB  - We report on label free, highly sensitive and selective electrochemical
      immunosensors based on one-dimensional 1D ZnO nanorods (ZnO-NRs) and two
      dimensional 2D ZnO nanoflakes (ZnO-NFs) which were synthesized on Au-coated
      substrates using simple one step sonochemical approach. Selective detection of
      cortisol using cyclic voltammetry (CV) is achieved by immobilizing anti-cortisol
      antibody (Anti-C(ab)) on the ZnO nanostructures (NSs). 1D ZnO-NRs and 2D ZnO-NFs
      provide unique sensing advantages over bulk materials. While 1D-NSs boast a high
      surface area to volume ratio, 2D-NSs with large area in polarized (0001) plane
      and high surface charge density could promote higher Anti-C(ab) loading and thus
      better sensing performance. Beside large surface area, ZnO-NSs also exhibit
      higher chemical stability, high catalytic activity, and biocompatibility. TEM
      studies showed that both ZnO-NSs are single crystalline oriented in (0001) plane.
      The measured sensing parameters are in the physiological range with a sensitivity
      of 11.86 uA/M exhibited by ZnO-NRs and 7.74 uA/M by ZnO-NFs with the lowest
      detection limit of 1 pM which is 100 times better than conventional enzyme-linked
      immunosorbant immunoassay (ELISA). ZnO-NSs based cortisol immunosensors were
      tested on human saliva samples and the performance were validated with
      conventional (ELISA) method which exhibits a remarkable correlation. The
      developed sensors can be integrated with microfluidic system and miniaturized
      potentiostat for point-of-care cortisol detection and such developed protocol can
      be used in personalized health monitoring/diagnostic.

PMID- 25064821
TI  - Plasmonic imaging of protein interactions with single bacterial cells.
AB  - Quantifying the interactions of bacteria with external ligands is fundamental to
      the understanding of pathogenesis, antibiotic resistance, immune evasion, and
      mechanism of antimicrobial action. Due to inherent cell-to-cell heterogeneity in
      a microbial population, each bacterium interacts differently with its
      environment. This large variability is washed out in bulk assays, and there is a
      need of techniques that can quantify interactions of bacteria with ligands at the
      single bacterium level. In this work, we present a label-free and real-time
      plasmonic imaging technique to measure the binding kinetics of ligand
      interactions with single bacteria, and perform statistical analysis of the
      heterogeneity. Using the technique, we have studied interactions of antibodies
      with single Escherichia coli O157:H7 cells and demonstrated a capability of
      determining the binding kinetic constants of single live bacteria with ligands,
      and quantify heterogeneity in a microbial population. 

PMID- 25064822
TI  - Protective effects of arjunolic acid against cardiac toxicity induced by oral
      sodium nitrite: effects on cytokine balance and apoptosis.
AB  - AIMS: Sodium nitrite, a preservative used in meat products, helps in the
      production of free radicals, leading to increased lipid peroxidation, which plays
      a vital role in posing toxic effects in different body organs. On the other hand,
      arjunolic acid possesses antioxidant properties and plays protective roles
      against chemically induced organ pathophysiology. We investigated the effect of
      sodium nitrite on cardiac tissue in rats on the inflammatory cytokine balance and
      the type of induced apoptosis, and we analyzed the protective role of arjunolic
      acid. MAIN METHODS: Sixty adult male Sprague-Dawley rats were injected with
      80mg/kg sodium nitrite in the presence/absence of arjunolic acid (100 and
      200mg/kg). Cardiac pro-inflammatory cytokines (TNF-alpha and IL-1beta), c
      reactive protein (CRP) and anti-inflammatory cytokines (IL-4 and IL-10) were
      measured by ELISA. Cardiac mitochondrial activity (cytochrome-C-oxidase), JNK
      activation and apoptosis (caspase-3, caspase-8 and caspase-9) were assessed. KEY
      FINDINGS: Sodium nitrite resulted in increased TNF-alpha (1.6-fold), IL-1beta
      (3.7-fold) and CRP (2.4-fold) levels accompanied by 52%, 59% and 40% reductions
      in IL-10, IL-4 and cytochrome-C-oxidase, respectively, as well as enhanced JNK,
      caspase-3, caspase-8 and caspase-9 activities. Arjunolic acid markedly
      ameliorated these effects. SIGNIFICANCE: Arjunolic acid attenuated sodium nitrite
      induced cardiac damage in rats and restored the normal balance between pro- and
      anti-inflammatory cytokines. Moreover, arjunolic acid protected cardiac tissues
      from both extrinsic and intrinsic cell death pathways.

PMID- 25064823
TI  - Mathematical modeling of physiological systems: an essential tool for discovery.
AB  - Mathematical models are invaluable tools for understanding the relationships
      between components of a complex system. In the biological context, mathematical
      models help us understand the complex web of interrelations between various
      components (DNA, proteins, enzymes, signaling molecules etc.) in a biological
      system, gain better understanding of the system as a whole, and in turn predict
      its behavior in an altered state (e.g. disease). Mathematical modeling has
      enhanced our understanding of multiple complex biological processes like enzyme
      kinetics, metabolic networks, signal transduction pathways, gene regulatory
      networks, and electrophysiology. With recent advances in high throughput data
      generation methods, computational techniques and mathematical modeling have
      become even more central to the study of biological systems. In this review, we
      provide a brief history and highlight some of the important applications of
      modeling in biological systems with an emphasis on the study of excitable cells.
      We conclude with a discussion about opportunities and challenges for mathematical
      modeling going forward. In a larger sense, the review is designed to help answer
      a simple but important question that theoreticians frequently face from
      interested but skeptical colleagues on the experimental side: "What is the value
      of a model?"

PMID- 25064824
TI  - Antitumor effect of soybean lectin mediated through reactive oxygen species
      dependent pathway.
AB  - AIMS: The present study evaluated the potential role of soybean lectin's (SBL)
      anticancer effect in vitro in different cancer cell lines and the therapeutic
      effectiveness in vivo in Dalton's lymphoma (DL) bearing mice model. MAIN METHODS:
      The effect of SBL on cell growth and viability was measured using MTT assay in
      different cancer cells in vitro. Apoptosis, autophagic cell death, DNA-damaging
      potential and reactive oxygen species (ROS) were analyzed in HeLa cells. The in
      vivo efficacy of SBL was demonstrated in Dalton's lymphoma (DL) bearing mice. KEY
      FINDINGS: SBL demonstrated clear, strong antiproliferative activity without
      affecting normal cells; however, heat denaturation of SBL diminished the
      antiproliferative efficacy of molecule as demonstrated by MTT assay. A sharp
      74.51 +/- 3.5% and 82.95 +/- 5.8% inhibition of tumor cell proliferation in DL
      mice occurred when SBL was administered at a dosage of 1 and 2mg/kg body weight
      (i.p.), respectively, for ten days with the induction of autophagic and apoptotic
      cell death. An in vitro investigation revealed that SBL-mediated autophagy,
      apoptosis and DNA damage in HeLa cells were inflicted through the generation of
      ROS in a dose-dependent manner. Interestingly, pre-treating HeLa cells with N
      acetylcysteine (NAC), a typical ROS scavenger, led to a noticeable reduction in
      SBL-induced autophagy, apoptosis and DNA-damaging activities, suggesting that
      SBL's antitumor potential was governed by ROS activation. SIGNIFICANCE: In this
      study, we evaluated the apoptotic, autophagic death, and DNA-damaging effects of
      SBL in cancer cells, which may have the potential to be used as a phyto-derived
      protein for cancer therapy.

PMID- 25064825
TI  - Endogenous alpha-crystallin inhibits expression of caspase-3 induced by hypoxia
      in retinal neurons.
AB  - AIM: To investigate the expression of endogenous, hypoxic stress-induced alpha
      crystallin and caspase-3 in rat retinal neurons in vitro. MAIN METHODS: Retinal
      neurons were cultured from Long-Evans rats. The expression of endogenous alpha
      crystallin was analyzed by immunohistochemistry and reverse transcriptase
      polymerase chain reaction (RT-PCR). Furthermore, hypoxic exposure was performed
      in cultured cells, and the expression of endogenous alpha-crystallin and caspase
      3 was assayed by Western blotting. KEY FINDINGS: Positive alpha-crystallin
      staining was observed in cultured retinal neurons, and expression of endogenous
      alpha-crystallin mRNA peaked 3-5d after inoculation (P<0.05). Moreover,
      endogenous, hypoxic stress-induced alpha-crystallin expression increased
      gradually, peaking 6h after hypoxia. The expression was more abundant compared to
      the control (P<0. 01) and was associated with a decrease in caspase-3 expression
      (P<0. 05). SIGNIFICANCE: The present study demonstrates that the expression of
      endogenous alpha-crystallin in retinal neurons, especially over-expression
      induced by hypoxic stress, results in the down regulation of caspase-3. The data
      suggest that endogenous alpha-crystallin may act as an endogenous neuroprotective
      factor in retinal neurons.

PMID- 25064826
TI  - Longitudinal strain of right ventricular free wall by 2-dimensional speckle
      tracking echocardiography is useful for detecting pulmonary hypertension.
AB  - AIMS: Echocardiography is widely used for screening pulmonary hypertension (PH).
      More recently developed two-dimensional speckle-tracking echocardiography (2D
      STE) can assess regional deformation of the myocardium and is useful for
      detecting left ventricular dysfunction. However, its usefulness to assess right
      ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was
      to investigate the ability of peak systolic strain (PSS) and post-systolic strain
      index (PSI) at the RV free wall determined by 2D-STE to detect PH. MAIN METHODS:
      Thirty-six images (27 images from PH patients, nine from patients with connective
      tissue disease without PH) obtained by 2D-STE were analysed. We investigated the
      relationship between RV hemodynamics measured by right heart catheterization and
      PSS, PSI and other echocardiographic parameters reflecting RV overload including
      RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure
      gradient (TRPG). KEY FINDINGS: PSS, PSI, RVDd and TRPG were all correlated with
      mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR).
      Furthermore, when PSS and MPAP were measured twice, the change in PSS was
      correlated with the change in MPAP (r=0.633, p=0.037). Multivariate logistic
      regression analysis identified PSS as the only independent factor associated with
      MPAP >= 35mmHg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017-2.567;
      p=0.042] and PVR >= 400dyn.s.cm(-5) (OR, 1.804; 95% CI 1.131-2.877; p=0.013).
      Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was
      -20.75%, based on receiver operating characteristic curve analysis. SIGNIFICANCE:
      PSS of the RV free wall might serve as a useful non-invasive indicator of PH.

PMID- 25064827
TI  - Intrathecal lidocaine neurotoxicity: combination with bupivacaine and ropivacaine
      and effect of nerve growth factor.
AB  - AIMS: The study aims to investigate the neurotoxicity induced by combined use of
      intrathecal lidocaine with bupivacaine and ropivacaine, and to examine the effect
      of nerve growth factor (NGF) on lidocaine-induced neurotoxicity. MAIN METHODS:
      All rats received intrathecal infusion of anesthetics and NGF. To study the
      neurotoxicity of combined use of lidocaine with bupivacaine and ropivacaine, rats
      received saline, 5% lidocaine, 1.065% bupivacaine, 1.5% ropivacaine, 5%
      lidocaine+bupivacaine, or 5% lidocaine+1.5% ropivacaine. To study the
      neurotoxicity of different proportions of lidocaine and bupivacaine, mixtures
      were made by mixing 10% lidocaine and 2.5% bupivacaine in ratios of 1:3, 1:2,
      1:1, 2:1 and 3:1 by volume. To study the effect of NGF on lidocaine-induced
      neurotoxicity, rats received saline or 10 MUg NGF for 1, 2, 5 and 8 days. KEY
      FINDINGS: The neurotoxicity of lidocaine was significantly increased when
      combined with ropivacaine. A mixture of lidocaine and bupivacaine in a ratio of
      <=1:1 did not significantly increase lidocaine-induced neurotoxicity. NGF
      significantly reduced lidocaine-induced neurobehavioral and morphological damage
      in the spinal cord. This was accompanied by downregulation of caspase 3
      expression. SIGNIFICANCE: Ropivacaine is not safe when intrathecally administered
      with lidocaine at the concentrations used in this study. Bupivacaine may be
      safely used with lidocaine at a ratio of 1:1. NGF can reduce lidocaine-induced
      neurotoxicity, possibly via inhibition of caspase 3-mediated apoptosis.

PMID- 25064828
TI  - Tanshinone IIA dampens the cell proliferation induced by ischemic insult in rat
      astrocytes via blocking the activation of HIF-1alpha/SDF-1 signaling.
AB  - AIMS: Tanshinone IIA (TSA) has been reported to protect neurons and microvascular
      endothelial cells against ischemic injury. However, the effect of TSA on
      astrocytes in response to ischemic injury is not clear. The aims of this study
      were to evaluate the effect of TSA on astrocytes following ischemic insult. MAIN
      METHODS: Primary cultured rat astrocytes were treated with oxygen-glucose
      deprivation (OGD) followed by recovery. Cell death was measured by lactate
      dehydrogenase assay. Astrocyte proliferation was determined by cell viability
      assay, cell counting and 5-bromo-2-deoxyuridine incorporation assay. The glial
      fibrillary acidic protein (GFAP) expression was assessed by immunocytochemistry.
      Stromal cell-derived factor-1 (SDF-1) secretion from astrocytes was measured by
      enzyme linked immunosorbent assay. The expressions of hypoxia inducible factor
      1alpha (HIF-1alpha), SDF-1, GFAP and the phosphorylation of Akt and extracellular
      regulated protein kinase (Erk) 1/2 were evaluated by immunoblot assay.
      Quantitative RT-PCR was used to assess the mRNA expression of HIF-1alpha and SDF
      1. KEY FINDINGS: Mild OGD (2 h-OGD) did not induce astrocyte injury but
      proliferation at 48 and 72 h after recovery. Mild OGD also induced the
      accumulation of HIF-1alpha, the subsequent expression and secretion of SDF-1,
      resulting in the phosphorylation of Erk1/2 and Akt. TSA attenuated astrocyte
      proliferation and significantly decreased the OGD-induced accumulation of HIF
      1alpha and SDF-1, then blocked the downstream signaling, Erk1/2 and Akt
      activation. SIGNIFICANCE: TSA inhibits the astrocyte proliferation induced by sub
      lethal ischemic insult via blocking the activation of HIF-1alpha/SDF-1 pathway.
      This finding suggests that TSA may be a potential therapeutic option for gliosis
      after cerebral ischemia.

PMID- 25064830
TI  - Why did this happen to me? Religious believers' and non-believers' teleological
      reasoning about life events.
AB  - People often believe that significant life events happen for a reason. In three
      studies, we examined evidence for the view that teleological beliefs reflect a
      general cognitive bias to view the world in terms of agency, purpose, and design.
      Consistent with this hypothesis, we found that individual differences in
      mentalizing ability predicted both the tendency to believe in fate (Study 1) and
      to infer purposeful causes of one's own life events (Study 2). In addition,
      people's perception of purpose in life events was correlated with their
      teleological beliefs about nature, but this relationship was driven primarily by
      individuals' explicit religious and paranormal beliefs (Study 3). Across all
      three studies, we found that while people who believe in God hold stronger
      teleological beliefs than those who do not, there is nonetheless evidence of
      teleological beliefs among non-believers, confirming that the perception of
      purpose in life events does not rely on theistic belief. These findings suggest
      that the tendency to perceive design and purpose in life events-while moderated
      by theistic belief-is not solely a consequence of culturally transmitted
      religious ideas. Rather, this teleological bias has its roots in certain more
      general social propensities. 

PMID- 25064831
TI  - Anger responses to psychosocial stress predict heart rate and cortisol stress
      responses in men but not women.
AB  - While previous research has suggested that anger and fear responses to stress are
      linked to distinct sympathetic nervous system (SNS) stress responses, little is
      known about how these emotions predict hypothalamus-pituitary-adrenal (HPA) axis
      reactivity. Further, earlier research primarily relied on retrospective self
      report of emotion. The current study aimed at addressing both issues in male and
      female individuals by assessing the role of anger and fear in predicting heart
      rate and cortisol stress responses using both self-report and facial coding
      analysis to assess emotion responses. We exposed 32 healthy students (18 female;
      19.6+/-1.7 yr) to an acute psychosocial stress paradigm (TSST) and measured heart
      rate and salivary cortisol levels throughout the protocol. Anger and fear before
      and after stress exposure was assessed by self-report, and video recordings of
      the TSST were assessed by a certified facial coder to determine emotion
      expression (FACS). Self-reported emotions and emotion expressions did not
      correlate (all p>.23). Increases in self-reported fear predicted blunted cortisol
      responses in men (beta=0.41, p=.04). Also for men, longer durations of anger
      expression predicted exaggerated cortisol responses (beta=0.67 p=.004), and more
      anger incidences predicted exaggerated cortisol and heart rate responses
      (beta=0.51, p=.033; beta=0.46, p=.066, resp.). Anger and fear did not predict SNS
      or HPA activity for females (all p>.23). The current differential self-report and
      facial coding findings support the use of multiple modes of emotion assessment.
      Particularly, FACS but not self-report revealed a robust anger-stress association
      that could have important downstream health effects for men. For women, future
      research may clarify the role of other emotions, such as self-conscious
      expressions of shame, for physiological stress responses. A better understanding
      of the emotion-stress link may contribute to behavioral interventions targeting
      health-promoting ways of responding emotionally to stress.

PMID- 25064832
TI  - Endosomal GPCR signaling turned off by negative feedback actions of PKA and v
      ATPase.
AB  - The PTH receptor is to our knowledge one of the first G protein-coupled receptor
      (GPCR) found to sustain cAMP signaling after internalization of the ligand
      receptor complex in endosomes. This unexpected model is adding a new dimension on
      how we think about GPCR signaling, but its mechanism is incompletely understood.
      We report here that endosomal acidification mediated by the PKA action on the v
      ATPase provides a negative feedback mechanism by which endosomal receptor
      signaling is turned off. 

PMID- 25064833
TI  - The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity.
AB  - Genotoxic chemotherapy is the most common cancer treatment strategy. However, its
      untargeted generic DNA-damaging nature and associated systemic cytotoxicity
      greatly limit its therapeutic applications. Here, we used a haploid genetic
      screen in human cells to discover an absolute dependency of the clinically
      evaluated anticancer compound YM155 on solute carrier family member 35 F2
      (SLC35F2), an uncharacterized member of the solute carrier protein family that is
      highly expressed in a variety of human cancers. YM155 generated DNA damage
      through intercalation, which was contingent on the expression of SLC35F2 and its
      drug-importing activity. SLC35F2 expression and YM155 sensitivity correlated
      across a panel of cancer cell lines, and targeted genome editing verified SLC35F2
      as the main determinant of YM155-mediated DNA damage toxicity in vitro and in
      vivo. These findings suggest a new route to targeted DNA damage by exploiting
      tumor and patient-specific import of YM155. 

PMID- 25064834
TI  - Identification of antihyperlipidemic constituents from the roots of Rubia
      yunnanensis Diels.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Rubia yunnanensis Diels (Rubiaceae)
      have been used as an alternative for Rubia cordifolia for the treatment of
      various diseases including cardiovascular disease and metabolic disease for a
      long history in traditional Chinese medicine. To evaluate antihyperlipidemic
      activity of the roots of Rubia. yunnanensis Diels and to identify active
      compounds from the active fraction. MATERIAL AND METHODS: Antihyperlipidemic
      effects of extract and compounds of the roots of Rubia yunnanensis were studied
      in HepG2 cells and in vivo model in olive oil-loaded mice. The isolation of
      compounds was conducted using various chromatographic methods and the structures
      of the isolated compounds were elucidated by NMR and MS techniques. RESULTS:
      Methanol extract and ethyl acetate fraction of Rubia yunnanensis potently
      decreased the triglycerides accumulation in HepG2 cells and the methanol extract
      of Rubia yunnanensis (125, 250 and 500 mg/kg) significantly inhibited the TG
      elevation in a dose dependent manner in olive oil-loaded mice. Through various
      chromatographic methods, twenty-three compounds (1-23) were isolated in which
      arborinane-type triterpenoids and a free anthraquinone potently inhibited TG
      levels in HepG2 cells. CONCLUSION: Arborinane-type triterpenoids, especial
      rubiarbonone C (16) and an anthraquinone, 2-methyl-1, 3, 6-trihydroxy-9, 10
      anthraquinone (MTHA) (22) were identified as the main active compounds
      responsible for antihyperlipidemic activity. Based on these findings, we proposed
      that the extract of Rubia yunnanensis and its active components, arborinane-type
      triterpenoids and the free anthraquinone might be beneficial in the treatment and
      prevention of hyperlipidemic disease.

PMID- 25064829
TI  - Revisiting the matricellular concept.
AB  - The concept of a matricellular protein was first proposed by Paul Bornstein in
      the mid-1990s to account for the non-lethal phenotypes of mice with inactivated
      genes encoding thrombospondin-1, tenascin-C, or SPARC. It was also recognized
      that these extracellular matrix proteins were primarily counter or de-adhesive.
      This review reappraises the matricellular concept after nearly two decades of
      continuous investigation. The expanded matricellular family as well as the
      diverse and often unexpected functions, cellular location, and interacting
      partners/receptors of matricellular proteins are considered. Development of
      therapeutic strategies that target matricellular proteins are discussed in the
      context of pathology and regenerative medicine. 

PMID- 25064835
TI  - Severity of khat dependence among adult khat chewers: the moderating influence of
      gender and age.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The escalating use of khat (Catha edulis) in East
      Africa and Arabia is a major concern for public health. Yet little is known about
      the impact of khat on behavior. There has been no study in the region to assess
      the extent to which dependence syndrome is associated with khat use in this
      population. AIM OF THE STUDY: To examine psychometric properties of the Severity
      of Dependence Scale-Khat (SDS-khat), gender differences in patterns of khat use
      and dependence, and the extent to which age moderated the link between gender and
      khat dependence. MATERIALS AND METHODS: Two-hundred and seventy khat chewers
      recruited in two Yemeni cities completed face-to-face interviews asking about
      demographics and patterns of khat use. Validity of SDS-khat was examined by the
      principle component analysis and reliability of the scale was tested by
      Cronbach's alpha. A series of chi-square tests and analysis of variances (ANOVAs)
      were conducted to examine gender differences in khat use variables. RESULTS: The
      results indicated that the mean age of khat chewers was 30.52 years (95% CI:
      29.34, 31.70) and 52% of them were males. The SDS-khat was found to have two
      factors with moderate reliability. This pattern was consistent when the analysis
      was conducted in the entire sample and in each gender. Male khat chewers reported
      more symptoms related to khat dependence than female chewers. A significant
      gender by age interaction in SDS-khat levels (p=0.013) revealed a positive
      association between age and khat dependence in women only. CONCLUSION: These
      results provide initial support for the use of SDS-khat in the assessment of khat
      dependence in Yemen. Gender differences in khat use patterns and dependence
      observed in this study call the need for more studies carefully examining the
      role of gender in khat research.

PMID- 25064837
TI  - Trajectories of pain and functional disability in CBT for pediatric chronic pain:
      is statistically significant change meaningful to patients and families?

PMID- 25064836
TI  - The role of perceived injustice in the prediction of pain and function after
      total knee arthroplasty.
AB  - Emerging evidence suggests that the appraisal of pain and disability in terms of
      justice-related themes contributes to adverse pain outcomes. To date, however,
      research on the relation between perceived injustice and pain outcomes has
      focused primarily on individuals with musculoskeletal injuries. The primary aim
      of this study was to investigate the role of perceived injustice in the
      prediction of pain and disability after total knee arthroplasty (TKA). The study
      sample consisted of 116 individuals (71 women, 45 men) with osteoarthritis of the
      knee scheduled for TKA. Participants completed measures of pain severity,
      physical disability, perceptions of injustice, pain catastrophizing, and fear of
      movement before surgery, and measures of pain and disability 1 year after
      surgery. Prospective multivariate analyses revealed that perceived injustice
      contributed modest but significant unique variance to the prediction of
      postsurgical pain severity, beyond the variance accounted for by demographic
      variables, comorbid health conditions, presurgical pain severity, pain
      catastrophizing, and fear of movement. Pain catastrophizing contributed
      significant unique variance to the prediction of postsurgical disability. The
      current findings add to a growing body of evidence supporting the prognostic
      value of perceived injustice in the prediction of adverse pain outcomes. The
      results suggest that psychosocial interventions designed to target perceptions of
      injustice and pain catastrophizing before surgery might contribute to more
      positive recovery trajectories after TKA.

PMID- 25064838
TI  - CYP17A1 gene polymorphisms and environmental exposure to organochlorine
      pesticides contribute to the risk of small for gestational age.
AB  - OBJECTIVES: The cytochrome P-450c17alpha enzyme encoded by the cytochrome P
      450c17alpha (CYP17A1) gene plays a role in oestrogen synthesis. Genetic variation
      in the maternal CYP17A1 gene leads to differences in oestrogen level that affect
      fetal growth and cause small for gestational age (SGA). Organochlorine pesticides
      (OCPs) are endocrine disruptors that alter the normal oestrogen-progesterone
      balance, and are associated with adverse reproductive outcomes. This study was
      designed to investigate the effect of the gene-environment interaction between
      maternal CYP17A1 gene polymorphisms and maternal and cord OCP levels on the risk
      of SGA. STUDY DESIGN: Maternal and cord blood samples of 50 term SGA cases (birth
      weight <10th percentile for gestational age as per Lubchenco's growth chart) and
      50 normal pregnancies (controls) were collected. Women with occupational exposure
      to OCPs, anaemia, hypertension, antiphospholipid antibody syndrome, medical
      disease, parity of more than four, or a history of smoking, alcohol consumption
      or chronic drug intake were excluded from both groups. Maternal and cord blood
      samples were collected at the time of delivery or after delivery, respectively.
      The OCP levels of the samples were analyzed using a gas chromatography system
      equipped with an electron capture detector, and polymerase chain reaction
      restriction fragment length polymorphism was used for polymorphic analysis of the
      CYP17A1 gene. RESULTS: Significantly (p<0.05) higher levels of alpha
      hexachlorocyclohexane (HCH), beta-HCH and gamma-HCH were found in maternal and
      cord blood samples of the SGA cases compared with the controls. The frequency of
      the A1A2/A2A2 genotype was significantly lower [p=0.041, odds ratio (OR) 0.421,
      95% confidence interval (CI) 0.184-0.966] in the SGA cases compared with the
      controls. When gene-environment interactions between CYP17A1 gene polymorphisms
      and OCP levels were considered, a significant (p=0.004) association was found
      between a high level of endosulfan in cord blood and the A1A1 (wild-type)
      genotype of CYP17A1, leading to an estimated reduction in birth weight of 315g.
      CONCLUSIONS: Higher OCP levels and the A1A1 genotype of CYP17A1 in pregnant women
      may be considered as important aetiological factors in idiopathic SGA. This study
      provides evidence that genetic variation and its interaction with environmental
      exposure may increase the risk of SGA. Further studies are needed with a larger
      sample size, incorporating other gene polymorphisms and environmental exposures,
      to strengthen these observations.

PMID- 25064839
TI  - Novel NLRP12 mutations associated with intestinal amyloidosis in a patient
      diagnosed with common variable immunodeficiency.
AB  - Heterozygous mutations in the NLRP12 gene have been found in patients with
      systemic auto-inflammatory diseases. However, the NLRP12-associated periodic
      fever syndromes show a wide clinical spectrum, including patients without
      classical diagnostic symptoms. Here, we report on a 20-year-old female patient
      diagnosed with common variable immunodeficiency (CVID), who developed intestinal
      amyloidosis and carried novel compound heterozygous mutations in NLRP12,
      identified by whole exome and transcriptome sequencing. CVID is a primary
      immunodeficiency characterized by low serum immunoglobulins, recurrent bacterial
      infections and development of malignancy, but it also presents with a magnitude
      of autoimmune features. Because of the unspecific heterogeneous clinical features
      of the disease, a delay in diagnosis is common. Secondary, inflammatory (AA type)
      amyloidosis has infrequently been observed in CVID patients. Based on our case
      observation and a critical review of the literature, we suggest that NLRP12
      mutations might account for a small fraction of CVID patients with severe auto
      inflammatory complications. 

PMID- 25064840
TI  - Characterization of type II thioesterases involved in natamycin biosynthesis in
      Streptomyces chattanoogensis L10.
AB  - The known functions of type II thioesterases (TEIIs) in type I polyketide
      synthases (PKSs) include selecting of starter acyl units, removal of aberrant
      extender acyl units, releasing of final products, and dehydration of polyketide
      intermediates. In this study, we characterized two TEIIs (ScnI and PKSIaTEII)
      from Streptomyces chattanoogensis L10. Deletion of scnI in S. chattanoogensis L10
      decreased the natamycin production by about 43%. Both ScnI and PKSIaTEII could
      remove acyl units from the acyl carrier proteins (ACPs) involved in the natamycin
      biosynthesis. Our results show that the TEII could play important roles in both
      the initiation step and the elongation steps of a polyketide biosynthesis; the
      intracellular TEIIs involved in different biosynthetic pathways could complement
      each other. 

PMID- 25064841
TI  - Dynein-dependent transport of spindle assembly checkpoint proteins off
      kinetochores toward spindle poles.
AB  - A predominant mechanism of spindle assembly checkpoint (SAC) silencing is dynein
      mediated transport of certain kinetochore proteins along microtubules. There are
      still conflicting data as to which SAC proteins are dynein cargoes. Using two ATP
      reduction assays, we found that the core SAC proteins Mad1, Mad2, Bub1, BubR1,
      and Bub3 redistributed from attached kinetochores to spindle poles, in a dynein
      dependent manner. This redistribution still occurred in metaphase-arrested cells,
      at a time when the SAC should be satisfied and silenced. Unexpectedly, we found
      that a pool of Hec1 and Mis12 also relocalizes to spindle poles, suggesting KMN
      components as additional dynein cargoes. The potential significance of these
      results for SAC silencing is discussed. 

PMID- 25064842
TI  - New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein
      kinase signaling.
AB  - As a well-characterized master player in epigenetic regulatory network, EZH2 is
      widely implicated in the development of many malignancies. We previously found
      that EZH2 promoted Wnt/beta-catenin activation through downregulation of CXXC4
      expression. In this report, we demonstrated that CXXC4 inhibited MAPK signaling
      through binding to ERK-1/2 and abrogating the interaction of ERK 1/2 with MEK1/2.
      L183, the critical residue in CXXC4 ERK D domain, was found to be essential for
      CXXC4-ERK 1/2 interaction and the growth inhibitory effect of CXXC4 in human
      cancer cells. In summary, CXXC4 directly disrupted MEK1/2-ERK 1/2 interaction to
      inactivate MAPK signaling. L183 site is indispensable for the binding of CXXC4 to
      ERK1/2 and growth inhibitory effect of CXXC4. Therefore, EZH2 can activate MAPK
      signaling by inhibiting CXXC4 expression.

PMID- 25064843
TI  - Phospholipase D2 downregulation induces cellular senescence through a reactive
      oxygen species-p53-p21Cip1/WAF1 pathway.
AB  - The expression of phospholipase D1 (PLD1) and PLD2 were found to decrease at the
      transcription level during both replicative and premature senescence in human
      lung fibroblast IMR-90 cells. Knockdown of PLD2 dramatically induced senescent
      phenotype in proliferating IMR-90 cells and wild-type HCT116 colon cancer cells,
      whereas this response was nearly abolished in p53- or p21(Cip1/WAF1)-null HCT116
      cells. PLD2 knockdown increased the intracellular reactive oxygen species (ROS).
      Antioxidant N-acetyl-L-cysteine, NADPH oxidase inhibitor apocynin, and p22(phox)
      small interfering RNA (siRNA) reduced ROS generation and thus suppressed the
      appearance of senescence markers. Elevated CK2 alpha subunit (CK2alpha)
      expression repressed PLD2 downregulation-mediated senescence. PLD2 overexpression
      increased protein kinase CK2 (also known as casein kinase 2) (CK2) activity.
      Taken together, these results show that PLD2 downregulation causes senescence
      through the p53-p21(Cip1/WAF1) pathway by stimulating ROS production, which is
      induced by CK2 inhibition.

PMID- 25064844
TI  - Crystal structure of the leucine-rich repeat domain of the NOD-like receptor
      NLRP1: implications for binding of muramyl dipeptide.
AB  - The NOD-like receptor NLRP1 (NLR family, pyrin domain containing 1) senses the
      presence of the bacterial cell wall component l-muramyl dipeptide (MDP) inside
      the cell. We determined the crystal structure of the LRR domain of human NLRP1 in
      the absence of MDP to a resolution of 1.65A. The fold of the structure can be
      assigned to the ribonuclease inhibitor-like class of LRR proteins. We compared
      our structure with X-ray models of the LRR domains of NLRX1 and NLRC4 and a
      homology model of the LRR domain of NOD2. We conclude that the MDP binding site
      of NLRP1 is not located in the LRR domain.

PMID- 25064845
TI  - miR-137 effects on gastric carcinogenesis are mediated by targeting Cox-2
      activated PI3K/AKT signaling pathway.
AB  - The discovery of microRNAs (miRNAs) provided a new avenue for early diagnosis and
      treatment of GC. MiR-137 has been reported to be under-expressed and involved in
      various cell processes. However, the role of miR-137 in GC is less known. In this
      study, we show that miR-137 is under-expressed in GC and functions as a tumor
      suppressor through targeting Cyclooxygenase-2 (Cox-2), which subsequently
      suppresses the activation of PI3K/AKT signaling pathway both in vitro and in
      vivo. Moreover, restored Cox-2 expression partially abolished the tumor
      suppressive effects of miR-137 in GC cells, suggesting miR-137 may suppress GC
      carcinogenesis by targeting Cox-2. 

PMID- 25064846
TI  - The multifaceted regulation and functions of PKM2 in tumor progression.
AB  - Tumor cells undergo metabolic rewiring from oxidative phosphorylation towards
      aerobic glycolysis to maintain the increased anabolic requirements for cell
      proliferation. It is widely accepted that specific expression of the M2 type
      pyruvate kinase (PKM2) in tumor cells contributes to this aerobic glycolysis
      phenotype. To date, researchers have uncovered myriad forms of functional
      regulation for PKM2, which confers a growth advantage on the tumor cells to
      enable them to adapt to various microenvironmental signals. Here the richness of
      our understanding on the modulations and functions of PKM2 in tumor progression
      is reviewed, and some new insights into the paradoxical expression and functional
      differences of PKM2 in distinct cancer types are offered. 

PMID- 25064847
TI  - Contrasting effects of ethylene biosynthesis on induced plant resistance against
      a chewing and a piercing-sucking herbivore in rice.
AB  - Ethylene is a stress hormone with contrasting effects on herbivore resistance.
      However, it remains unknown whether these differences are plant- or herbivore
      specific. We cloned a rice 1-aminocyclopropane-1-carboxylic acid (ACC) synthase
      gene, OsACS2, whose transcripts were rapidly up-regulated in response to
      mechanical wounding and infestation by two important pests: the striped stem
      borer (SSB) Chilo suppressalis and the brown planthopper (BPH) Nilaparvata
      lugens. Antisense expression of OsACS2 (as-acs) reduced elicited ethylene
      emission, SSB-elicited trypsin protease inhibitor (TrypPI) activity, SSB-induced
      volatile release, and SSB resistance. Exogenous application of ACC restored
      TrypPI activity and SSB resistance. In contrast to SSB, BPH infestation increased
      volatile emission in as-acs lines. Accordingly, BPH preferred to feed and
      oviposit on wild-type (WT) plants--an effect that could be attributed to two
      repellent volatiles, 2-heptanone and 2-heptanol, that were emitted in higher
      amounts by as-acs plants. BPH honeydew excretion was reduced and natural enemy
      attraction was enhanced in as-acs lines, resulting in higher overall resistance
      to BPH. These results demonstrate that ethylene signaling has contrasting,
      herbivore-specific effects on rice defense responses and resistance against a
      chewing and a piercing-sucking insect, and may mediate resistance trade-offs
      between herbivores of different feeding guilds in rice.

PMID- 25064848
TI  - Timing is everything: highly specific and transient expression of a MAP kinase
      determines auxin-induced leaf venation patterns in Arabidopsis.
AB  - Mitogen-activated protein kinase (MAPK) cascades are universal signal
      transduction modules present in all eukaryotes. In plants, MAPK cascades were
      shown to regulate cell division, developmental processes, stress responses, and
      hormone pathways. The subgroup A of Arabidopsis MAPKs consists of AtMPK3, AtMPK6,
      and AtMPK10. AtMPK3 and AtMPK6 are activated by their upstream MAP kinase kinases
      (MKKs) AtMKK4 and AtMKK5 in response to biotic and abiotic stress. In addition,
      they were identified as key regulators of stomatal development and patterning.
      AtMPK10 has long been considered as a pseudo-gene, derived from a gene
      duplication of AtMPK6. Here we show that AtMPK10 is expressed highly but very
      transiently in seedlings and at sites of local auxin maxima leaves. MPK10 encodes
      a functional kinase and interacts with the upstream MAP kinase kinase (MAPKK)
      AtMKK2. mpk10 mutants are delayed in flowering in long-day conditions and in
      continuous light. Moreover, cotyledons of mpk10 and mkk2 mutants have reduced
      vein complexity, which can be reversed by inhibiting polar auxin transport (PAT).
      Auxin does not affect AtMPK10 expression while treatment with the PAT inhibitor
      HFCA extends the expression in leaves and reverses the mpk10 mutant phenotype.
      These results suggest that the AtMKK2-AtMPK10 MAPK module regulates venation
      complexity by altering PAT efficiency. 

PMID- 25064849
TI  - 'Silent' mitral cells dominate odor responses in the olfactory bulb of awake
      mice.
AB  - How wakefulness shapes neural activity is a topic of intense discussion. In the
      awake olfactory bulb, high activity with weak sensory-evoked responses has been
      reported in mitral/tufted cells (M/TCs). Using blind whole-cell recordings, we
      found 33% of M/TCs to be 'silent', yet still show strong sensory responses, with
      weak or inhibitory responses in 'active' neurons. Thus, a previously missed M/TC
      subpopulation can exert powerful influence over the olfactory bulb.

PMID- 25064850
TI  - Cerebellum involvement in cortical sensorimotor circuits for the control of
      voluntary movements.
AB  - Sensorimotor integration is crucial to perception and motor control. How and
      where this process takes place in the brain is still largely unknown. Here we
      analyze the cerebellar contribution to sensorimotor integration in the whisker
      system of mice. We identify an area in the cerebellum where cortical sensory and
      motor inputs converge at the cellular level. Optogenetic stimulation of this area
      affects thalamic and motor cortex activity, alters parameters of ongoing
      movements and thereby modifies qualitatively and quantitatively touch events
      against surrounding objects. These results shed light on the cerebellum as an
      active component of sensorimotor circuits and show the importance of sensorimotor
      cortico-cerebellar loops in the fine control of voluntary movements. 

PMID- 25064851
TI  - Anterior cingulate engagement in a foraging context reflects choice difficulty,
      not foraging value.
AB  - Previous theories predict that human dorsal anterior cingulate (dACC) should
      respond to decision difficulty. An alternative theory has been recently advanced
      that proposes that dACC evolved to represent the value of 'non-default', foraging
      behavior, calling into question its role in choice difficulty. However, this new
      theory does not take into account that choosing whether or not to pursue foraging
      like behavior can also be more difficult than simply resorting to a default. The
      results of two neuroimaging experiments show that dACC is only associated with
      foraging value when foraging value is confounded with choice difficulty; when the
      two are dissociated, dACC engagement is only explained by choice difficulty, and
      not the value of foraging. In addition to refuting this new theory, our studies
      help to formalize a fundamental connection between choice difficulty and foraging
      like decisions, while also prescribing a solution for a common pitfall in studies
      of reward-based decision making. 

PMID- 25064853
TI  - Anasarca, renal failure, hemoptysis, and rash in a 32-year-old male Mexican
      immigrant.

PMID- 25064852
TI  - Central amygdala PKC-delta(+) neurons mediate the influence of multiple
      anorexigenic signals.
AB  - Feeding can be inhibited by multiple cues, including those associated with
      satiety, sickness or unpalatable food. How such anorexigenic signals inhibit
      feeding at the neural circuit level is not completely understood. Although some
      inhibitory circuits have been identified, it is not yet clear whether distinct
      anorexigenic influences are processed in a convergent or parallel manner. The
      amygdala central nucleus (CEA) has been implicated in feeding control, but its
      role is controversial. The lateral subdivision of CEA (CEl) contains a
      subpopulation of GABAergic neurons that are marked by protein kinase C-delta (PKC
      delta). We found that CEl PKC-delta(+) neurons in mice were activated by diverse
      anorexigenic signals in vivo, were required for the inhibition of feeding by such
      signals and strongly suppressed food intake when activated. They received
      presynaptic inputs from anatomically distributed neurons activated by different
      anorexigenic agents. Our data suggest that CEl PKC-delta(+) neurons constitute an
      important node that mediates the influence of multiple anorexigenic signals. 

PMID- 25064855
TI  - Engineering the elongation factor Tu for efficient selenoprotein synthesis.
AB  - Selenocysteine (Sec) is naturally co-translationally incorporated into proteins
      by recoding the UGA opal codon with a specialized elongation factor (SelB in
      bacteria) and an RNA structural signal (SECIS element). We have recently
      developed a SECIS-free selenoprotein synthesis system that site-specifically-
      using the UAG amber codon--inserts Sec depending on the elongation factor Tu (EF
      Tu). Here, we describe the engineering of EF-Tu for improved selenoprotein
      synthesis. A Sec-specific selection system was established by expression of human
      protein O(6)-alkylguanine-DNA alkyltransferase (hAGT), in which the active site
      cysteine codon has been replaced by the UAG amber codon. The formed hAGT
      selenoprotein repairs the DNA damage caused by the methylating agent N-methyl-N'
      nitro-N-nitrosoguanidine, and thereby enables Escherichia coli to grow in the
      presence of this mutagen. An EF-Tu library was created in which codons specifying
      the amino acid binding pocket were randomized. Selection was carried out for
      enhanced Sec incorporation into hAGT; the resulting EF-Tu variants contained
      highly conserved amino acid changes within members of the library. The improved
      UTu-system with EF-Sel1 raises the efficiency of UAG-specific Sec incorporation
      to >90%, and also doubles the yield of selenoprotein production.

PMID- 25064856
TI  - Homodimerization of RBPMS2 through a new RRM-interaction motif is necessary to
      control smooth muscle plasticity.
AB  - In vertebrates, smooth muscle cells (SMCs) can reversibly switch between
      contractile and proliferative phenotypes. This involves various molecular
      mechanisms to reactivate developmental signaling pathways and induce cell
      dedifferentiation. The protein RBPMS2 regulates early development and plasticity
      of digestive SMCs by inhibiting the bone morphogenetic protein pathway through
      its interaction with NOGGIN mRNA. RBPMS2 contains only one RNA recognition motif
      (RRM) while this motif is often repeated in tandem or associated with other
      functional domains in RRM-containing proteins. Herein, we show using an extensive
      combination of structure/function analyses that RBPMS2 homodimerizes through a
      particular sequence motif (D-x-K-x-R-E-L-Y-L-L-F: residues 39-51) located in its
      RRM domain. We also show that this specific motif is conserved among its homologs
      and paralogs in vertebrates and in its insect and worm orthologs (CPO and MEC-8,
      respectively) suggesting a conserved molecular mechanism of action. Inhibition of
      the dimerization process through targeting a conserved leucine inside of this
      motif abolishes the capacity of RBPMS2 to interact with the translational
      elongation eEF2 protein, to upregulate NOGGIN mRNA in vivo and to drive SMC
      dedifferentiation. Our study demonstrates that RBPMS2 possesses an RRM domain
      harboring both RNA-binding and protein-binding properties and that the newly
      identified RRM-homodimerization motif is crucial for the function of RBPMS2 at
      the cell and tissue levels. 

PMID- 25064857
TI  - Crucial role of the Rcl1p-Bms1p interaction for yeast pre-ribosomal RNA
      processing.
AB  - The essential Rcl1p and Bms1p proteins form a complex required for 40S ribosomal
      subunit maturation. Bms1p is a GTPase and Rcl1p has been proposed to catalyse the
      endonucleolytic cleavage at site A2 separating the pre-40S and pre-60S maturation
      pathways. We determined the 2.0 A crystal structure of Bms1p associated with
      Rcl1p. We demonstrate that Rcl1p nuclear import depends on Bms1p and that the two
      proteins are loaded into pre-ribosomes at a similar stage of the maturation
      pathway and remain present within pre-ribosomes after cleavage at A2.
      Importantly, GTP binding to Bms1p is not required for the import in the nucleus
      nor for the incorporation of Rcl1p into pre-ribosomes, but is essential for early
      pre-rRNA processing. We propose that GTP binding to Bms1p and/or GTP hydrolysis
      may induce conformational rearrangements within the Bms1p-Rcl1p complex allowing
      the interaction of Rcl1p with its RNA substrate. 

PMID- 25064858
TI  - High-throughput mutagenesis reveals functional determinants for DNA targeting by
      activation-induced deaminase.
AB  - Antibody maturation is a critical immune process governed by the enzyme
      activation-induced deaminase (AID), a member of the AID/APOBEC DNA deaminase
      family. AID/APOBEC deaminases preferentially target cytosine within distinct
      preferred sequence motifs in DNA, with specificity largely conferred by a small 9
      11 residue protein loop that differs among family members. Here, we aimed to
      determine the key functional characteristics of this protein loop in AID and to
      thereby inform our understanding of the mode of DNA engagement. To this end, we
      developed a methodology (Sat-Sel-Seq) that couples saturation mutagenesis at each
      position across the targeting loop, with iterative functional selection and next
      generation sequencing. This high-throughput mutational analysis revealed dominant
      characteristics for residues within the loop and additionally yielded enzymatic
      variants that enhance deaminase activity. To rationalize these functional
      requirements, we performed molecular dynamics simulations that suggest that AID
      and its hyperactive variants can engage DNA in multiple specific modes. These
      findings align with AID's competing requirements for specificity and flexibility
      to efficiently drive antibody maturation. Beyond insights into the AID-DNA
      interface, our Sat-Sel-Seq approach also serves to further expand the repertoire
      of techniques for deep positional scanning and may find general utility for high
      throughput analysis of protein function. 

PMID- 25064859
TI  - Functional analysis of single-nucleotide polymorphisms in the regulation of
      coactivator-associated arginine methyltransferase 1 expression and plasma
      homocysteine levels.
AB  - BACKGROUND: Hyperhomocysteinemia is a risk factor for cardiovascular disease.
      Coactivator-associated arginine methyltransferase 1 (CARM1) participates in the
      synthesis of homocysteine, but whether the genetic variations regulate CARM1
      expression and homocysteine levels remains unknown. METHODS AND RESULTS:
      Functional analyses combined with an association study were conducted to identify
      the causal variant for CARM1 expression and homocysteine levels. Based on
      functional annotations obtained from Encyclopedia of DNA Elements, we selected 4
      potentially functional single-nucleotide polymorphisms in the CARM1 gene and
      investigated their effect on CARM1 transcription levels in vivo. rs117569851,
      located in the promoter region of CARM1, as well as rs12460421 and rs4804544, was
      associated with CARM1 expression levels, and the last 2 single-nucleotide
      polymorphisms were discovered in high linkage disequilibrium with rs117569851
      (r(2)=0.9 and 1.0) in our study sample. rs117569851 was further identified to be
      responsible for regulating CARM1 expression. The T allele disrupted the binding
      of early growth response-1, which led to the downregulation of transcriptional
      activity in vitro and CARM1 mRNA levels in vivo. In addition, rs117569851 was
      associated with plasma homocysteine levels in a Chinese population (n=406), with
      a 2.16 MUmol/L decrease per copy of T allele. CONCLUSIONS: The present study
      suggests that a noncoding variant in the CARM1-promoter functions as a regulator
      of gene transcription and homocysteine levels.

PMID- 25065002
TI  - CANDLE syndrome: an extended clinical spectrum.

PMID- 25065003
TI  - Primary bone marrow oedema syndrome: proposed outcome measures for pain and
      physical functioning.

PMID- 25065001
TI  - Circulating 25-hydroxyvitamin D level and risk of developing rheumatoid
      arthritis.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between
      preclinical circulating 25-hydroxyvitamin D [25(OH)D] and RA in two nested case
      control studies within the prospective cohort Nurses' Health Study (NHS) and NHS
      II (NHSII). METHODS: We included 166 women with RA and blood specimens collected
      3 months to 16 years prior to the first RA symptom and 490 matched controls (3:1,
      matched on age, date of blood draw, hormonal factors). We calculated the odds
      ratio (OR) and 95% CI for incident RA using conditional logistic regression
      multivariable adjusted models, including additional covariates for smoking
      status, parity and breastfeeding, alcohol consumption, BMI, median income and
      region of residence in the USA. We repeated analyses stratified by time from
      blood draw to RA diagnosis (3 months to <4 years or >=4 years) and meta-analysed
      estimates from the two cohorts using fixed effects models. RESULTS: Incident RA
      was confirmed in 120 NHS [mean age 63.8 years (s.d. 8.2)] and 46 NHSII
      participants [mean age 48.5 years (s.d. 4.7)]. Mean time from blood draw to RA
      diagnosis was 7.8 years (s.d. 4.2) for NHS and 4.2 years (s.d. 2.0) for NHSII
      participants. Meta-analysis of crude and multivariable-adjusted conditional
      logistic models did not show significant associations between circulating 25(OH)D
      and RA. However, among NHSII women with blood drawn between 3 months and <4 years
      prior to RA diagnosis, there was a 20% decreased risk of RA associated with each
      1 ng/ml increase in 25(OH)D [OR 0.80 (95% CI 0.64, 0.99)]. CONCLUSION: We did not
      observe a significant association between circulating 25(OH)D levels and RA,
      except for among a small subset of NHSII women with levels measured closest to RA
      diagnosis.

PMID- 25065004
TI  - Inflammatory arthropathy of the manubriosternal joint.

PMID- 25065005
TI  - Incidence and prevalence of inflammatory myopathies: a systematic review.
AB  - OBJECTIVES: . The aims of this study were to determine the incidence and
      prevalence of inflammatory myopathies (IMs), their epidemiological tendencies
      over time and their possible key determinants. METHODS: . All original articles
      in English or French regarding the prevalence and/or incidence of IMs were
      searched. The methods of case ascertainment, epidemiological analysis and
      diagnostic criteria were systematically analysed. RESULTS: . Forty-six articles
      published between 1966 and 2013 were found in which the incidence of IMs as a
      whole ranged from 1.16 to 19/million/year and their prevalence ranged from 2.4 to
      33.8 per 100 000 inhabitants. Methodological heterogeneities limited comparisons,
      although certain epidemiological tendencies were highlighted. The relative
      incidence of DM may follow a latitudinal gradient in the northern hemisphere that
      may be explained by the immunomodulatory action of ultraviolet radiation. The
      prevalence of sporadic inclusion body myositis (sIBM) was correlated with the
      frequency of HLA-DR3. Juvenile myositis onset was non-random over seasons and/or
      time, consistent with a role of infectious diseases, although other environmental
      factors may be involved. Disparities according to sex, age and geographical
      origin were also found. The frequency of IM increased over time, which may
      reflect progress in diagnostic performance, although there is still a need to
      increase the level of awareness with regard to these diseases, especially sIBM,
      as attested by its considerably delayed diagnosis. CONCLUSION: . This first
      systematic literature review confirms the rarity of IM and may highlight certain
      genetic and environmental determinants of IM. There is a need for uniformity in
      diagnostic and classification criteria as well as more exhaustive case
      ascertainment to refine IM epidemiology.

PMID- 25065006
TI  - Treatment of refractory polyarticular juvenile idiopathic arthritis with
      tacrolimus.

PMID- 25065007
TI  - Measurement properties of the Disability Rating Index in patients undergoing hip
      replacement.
AB  - OBJECTIVE: The aim of this study was to establish and validate the measurement
      properties of the Disability Rating Index (DRI) in a population of adults
      undergoing hip replacement. METHODS: One hundred and twenty-six adults
      participating in a randomized controlled trial completed the Oxford Hip Score,
      Harris Hip Score, DRI and EuroQol Group-Five Dimensions (EQ-5D) questionnaires at
      four time points. The structural validity of the DRI was assessed using principal
      component analysis. Cronbach's alpha was used to determine the internal
      consistency and scale reliability was also assessed. Correlation between the DRI
      and the other functional and health-related quality of life scales was used to
      check criterion validity. DRI responsiveness was estimated and the
      interpretability of the scale was also assessed by checking for edge effects.
      RESULTS: Results of analyses showed that the DRI was internally consistent
      (Cronbach's alpha = 0.92), had good association with both function-specific and
      general health-related quality of life scores and was sensitive to change
      (smallest detectable change = 2.7). No evidence of edge effects was found.
      Furthermore, structural assessment of the DRI revealed two novel subscales
      representing simple tasks and difficult tasks. CONCLUSIONS: The DRI is
      structurally valid, responsive and concurs with functional assessment in adults
      undergoing hip replacement.

PMID- 25065008
TI  - Influence of model and matrix on cytokine profile in rat and human.
AB  - OBJECTIVE: Emerging evidence indicates that low-grade inflammation is part of the
      clinical picture of OA and that there is a need to identify soluble biomarkers of
      ongoing inflammation in the joint from a translational aspect. The aim of this
      study was to compare levels of pro-inflammatory biomarkers in SF, serum and/or
      EDTA plasma. METHODS: SF and blood from rats subjected to Freund's complete
      adjuvant (FCA; n = 48) or monoiodoacetate (MIA; n = 88) monoarthritis and from
      control rats were collected over time. SF, EDTA plasma and serum were obtained
      from six individuals with OA of the knee and healthy controls. Levels of IL-6,
      KC/GRO, IL-8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory
      protein 3alpha (MIP-3alpha), IL-1beta, TNF and l(+)-lactate were assessed either
      by immune assay or by a colorimetric method. RESULTS: Elevated levels of
      biomarkers were shown in monoarthritic animals in SF compared with the control
      groups, although with considerably lower magnitude in the MIA groups, which also
      indicated a biphasic pattern. Levels of KC/GRO and MIP-3alpha in serum from the
      FCA model and IL-6 in the MIA model followed the pattern of SF. In serum samples
      from OA individuals, MIP-3alpha correlated significantly with levels in SF.
      CONCLUSION: While we found increased levels of markers in joint fluid and blood,
      no single systemic biochemical biomarkers that were a common denominator between
      the animal models and the patient material could be identified. Our data indicate
      that it is critical to delineate the temporal profile of multiple local and
      systemic factors in order to pinpoint soluble biomarkers for OA.

PMID- 25065009
TI  - Digital ulcers as a sentinel sign for early internal organ involvement in very
      early systemic sclerosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the presence of digital lesions
      in very early diagnosis of SSc (VEDOSS) patients and its possible association
      with internal organ involvement. METHODS: One hundred and ten VEDOSS patients
      were investigated for the presence of digital ulcers (DUs), digital pitting
      scars, calcinosis, necrosis or gangrene, nailfold videocapillaroscopic
      abnormalities, disease-specific autoantibodies (ACA and anti-topo I) and internal
      organ involvement. RESULTS: Four patients reported a history of digital pitting
      scars, while 25 patients presented an active DU or reported a history of DUs. In
      particular, 16 patients presented with active DUs (14/16 also reporting a history
      of previous DUs), while the other 9 patients reported a history of DUs only. A
      statistically significant association between DUs and oesophageal manometry
      alteration was found in the whole DU population, as well as in the history of DU
      and the presence of active DU with/without a history of DU subgroups (P < 0.01, P
      = 0.01 and P < 0.05, respectively). DUs were observed in VEDOSS patients with
      internal organ involvement but not in those without organ involvement.
      CONCLUSION: DUs are already present in VEDOSS patients characterized by internal
      organ involvement, significantly correlating and associating with
      gastrointestinal involvement. DUs may be a sentinel sign for early organ
      involvement in VEDOSS patients.

PMID- 25065010
TI  - The active metabolite of spleen tyrosine kinase inhibitor fostamatinib abrogates
      the CD4+ T cell-priming capacity of dendritic cells.
AB  - OBJECTIVES: Spleen tyrosine kinase (SYK) is a core signalling protein that drives
      inflammatory responses and is fundamental to the propagation of signals via
      numerous immune receptors, including the B cell receptor and Fc receptors (FcRs).
      Fostamatinib, a small molecule SYK inhibitor, has shown evidence of ameliorating
      inflammation in RA patients. We sought to understand how the active metabolite of
      fostamatinib, R406, affects the inflammatory response at the cellular level.
      METHODS: Antigen-specific in vivo systems and in vitro fluorescence microscopy
      were combined to investigate the effects of fostamatinib on antigen-specific
      interactions between dendritic cells (DCs) and CD4(+) T cells. RESULTS: Although
      it has previously been shown that R406 reduces the response of DCs to immune
      complexes (ICs), we found that fostamatinib failed to reduce specific CD4(+) T
      cell proliferation in mice after immunization with ICs. However, we observed in
      vitro that R406 reduces both the area and duration of cellular interactions
      between IC-activated DCs and specific CD4(+) T cells during the initial phase of
      cellular crosstalk. This led to diminished proliferation of antigen-specific
      CD4(+) T cells after R406 treatment compared with vehicle controls. This
      decreased proliferative capacity of CD4(+) T cells was accompanied by reduced
      expression of the co-stimulatory molecules, inducible T cell co-stimulator (ICOS)
      and PD-1, and abrogation of the production of inflammatory cytokines such as IFN
      gamma and IL-17. CONCLUSION: Our findings indicate a potential mechanism by which
      this compound may be effective in inhibiting FcR-driven CD4(+) T cell responses.

PMID- 25065011
TI  - Relationship between types of radiographic damage and disability in patients with
      rheumatoid arthritis in the EURIDISS cohort: a longitudinal study.
AB  - OBJECTIVE: The aim of this study was to assess if any of the different types of
      radiographic damage [true joint space narrowing (JSN), (sub)luxation and
      erosions] are preferentially related to disability in patients with RA. METHODS:
      Longitudinal data from 167 RA patients from the European Research on
      Incapacitating Diseases and Social Support study over 10 years were analysed to
      investigate the relationship between the three types of radiographic damage and
      disability [grip strength, HAQ and the dexterity scale in the Arthritis Impact
      Measurement Scales (AIMS)]. A longitudinal analysis including separate models per
      type of damage and joint group and combined models including all information was
      conducted. RESULTS: All types of damage were inversely related to grip strength
      in the analysis of separate models, but only true JSN independently remained
      statistically significant in the combined analysis [beta = -0.087 (95% CI -0.151,
      -0.022)]. Neither JSN, (sub)luxation nor erosions were associated with HAQ score,
      while erosions were associated with AIMS dexterity only in the analysis of
      separate models. After stratifying for hand joint group, erosions at MCP joints
      [beta = -0.288 (95% CI -0.556, -0.019)] and true JSN at the wrist [beta = -0.132
      (95% CI -0.234, -0.030)] were significantly related to grip strength. Erosions at
      the PIP [beta = 0.017 (95% CI 0.005, 0.028)] and MCP joints [beta = 0.114 (95% CI
      0.010, 0.217)] was the only type of damage associated with HAQ and AIMS
      dexterity, respectively. CONCLUSION: All types of radiographically visible joint
      damage interfere with important aspects of physical functions. True JSN is most
      closely related to hand function.

PMID- 25065012
TI  - Single-organ cutaneous small-vessel vasculitis according to the 2012 revised
      International Chapel Hill Consensus Conference Nomenclature of Vasculitides: a
      study of 60 patients from a series of 766 cutaneous vasculitis cases.
AB  - OBJECTIVE: Cutaneous vasculitis (CV) encompasses a wide group of entities
      characterized by inflammation of skin blood vessels. The term single-organ
      vasculitis was recently coined by the 2012 Chapel Hill Consensus Conference
      (CHCC) to define vasculitis affecting a single organ. To our knowledge there are
      no published reports on single-organ cutaneous small vessel vasculitis (SoCSVV).
      Our aim was to characterize this entity from a wide series of patients with CV.
      METHODS: We analysed cases of SoCSVV from a series of 766 patients with CV from a
      single university referral centre. According to 2012 CHCC, the following
      conditions were required to define SoCSVV: (i) skin biopsy showing characteristic
      leucocytoclastic vasculitis and (ii) vasculitis limited to skin. RESULTS: We
      included 60 patients (26 women and 34 men) with a mean age of 56 years. The main
      precipitating factors for SoCSVV were drugs [26 patients (52%)] and previous
      infection [17 patients (34%)]. The main clinical manifestations were palpable
      purpura (81.7%) and fever (18.3%). The most frequent laboratory findings were
      leucocytosis and elevated ESR. Nearly one-quarter of patients with SoCSVV
      required pharmacological therapy. Corticosteroids (15%) and NSAIDs (13.3%) were
      the main agents prescribed. After a median follow-up of 4 months, complete
      recovery was observed in all the patients, although relapses occurred in 8% of
      patients. CONCLUSION: SoCSVV defined according to the 2012 CHCC may be considered
      a benign disease usually associated with drugs and/or a previous infection.

PMID- 25065014
TI  - In vitro immunomodulatory effects of microencapsulated umbilical cord Wharton
      jelly-derived mesenchymal stem cells in primary Sjogren's syndrome.
AB  - OBJECTIVE: Human umbilical cord Wharton jelly-derived mesenchymal stem cells
      (hUCMS) are easy to retrieve in bulk. They may interact with immune cells by
      either cell contact or soluble factors. Little evidence is currently available on
      potential therapeutic application of hUCMS to systemic autoimmune disorders such
      as primary SS (pSS). We have recently developed an endotoxin-free alginate gel
      that can be used to microencapsulate different cell types for graft into non
      immunosuppressed hosts. We aimed to assess the in vitro effects of IFN-gamma
      pretreated microencapsulated (CpS)-hUCMS on T cells of pSS. METHODS: Ten pSS
      patients and 10 healthy donors were selected. Peripheral blood mononuclear cells
      (PBMCs) were obtained from venous blood to establish co-cultures with CpS-hUCMS.
      Lymphocyte proliferation and phenotypic analysis was performed by flow cytometry
      and real-time PCR on IFN-gamma-pretreated hUCMS was performed before PBMCs co
      culture. RESULTS: We found that CpS-hUCMS suppress pSS T cell proliferation and
      restore the Treg/Th17 ratio, thereby possibly positively impacting the pSS
      disease process. CONCLUSION: We have developed a new biohybrid drug delivery
      system that now waits for clinical application in autoimmune diseases, including
      pSS.

PMID- 25065015
TI  - Measuring flares in systemic lupus erythematosus.

PMID- 25065013
TI  - Old medications and new targeted therapies in systemic sclerosis.
AB  - SSc is a multiorgan disease with significant morbidity that is associated with
      poor health-related quality of life. Treatment of this condition is often organ
      based and non-curative. However, there are newer, potentially disease-modifying
      therapies available to treat certain aspects of the disease. This review focuses
      on old and new therapies in the management of SSc in clinical practice. 

PMID- 25065016
TI  - Prediction of flare-ups in IgG4-related disease.

PMID- 25065018
TI  - Depression in older people is underdiagnosed.
AB  - Depression is more common in old age than dementia yet is underdiagnosed and
      undertreated. It is important to recognise that patients may not always present
      in a typical way, features that may indicate depression include anxiety, a
      preoccupation with somatic symptoms, and a change in function. The presence of
      understandable triggers and causes should not deter GPs from offering treatment,
      as long as symptoms are pervasive and continuously persist beyond two weeks. Age
      related disabilities and changes to physical health are major risk factors for
      depression in older people. Vascular diseases, including stroke, MI and diabetes
      increase the risk of depression, both through direct effects on the brain and the
      psychological effects. Likewise, dementia is a risk factor for depression.
      Psychological factors such as loneliness and loss of a valued role, as well as
      social factors related to retirement, bereavement and reduced independence may
      also increase the risk. Patients with a previous history of depression and
      anxiety disorders are at increased risk of depression in later life. Assessment
      and diagnosis are largely based on a careful history. This should focus on
      eliciting current features of depression, which have been present for at least
      two weeks, and are associated with a significant change in function. It is
      important to exclude organic disorders including anaemia, B12 and folate
      deficiency, and hypothyroidism that may mimic symptoms of depressive disorder.
      Referral to specialist mental health services is indicated in the following
      cases: diagnostic difficulty, poor response to treatment, psychotic symptoms,
      significant psychiatric comorbidity or a risk of self-neglect or suicide.

PMID- 25065019
TI  - Gaining ground: Americans' health insurance coverage and access to care after the
      Affordable Care Act's first open enrollment period.
AB  - A new Commonwealth Fund survey finds that in the wake of the Affordable Care
      Act's first open enrollment period, significantly fewer working-age adults are
      uninsured than just before the sign-up period began, and many have used their new
      coverage to obtain needed care. The uninsured rate for people ages 19 to 64
      declined from 20 percent in the July-to-September 2013 period to 15 percent in
      the April-to-June 2014 period. An estimated 9.5 million fewer adults were
      uninsured. Young men and women drove a large part of the decline: the uninsured
      rate for 19-to-34-year-olds declined from 28 percent to 18 percent, with an
      estimated 5.7 million fewer young adults uninsured. By June, 60 percent of adults
      with new coverage through the marketplaces or Medicaid reported they had visited
      a doctor or hospital or filled a prescription; of these, 62 percent said they
      could not have accessed or afforded this care previously.

PMID- 25065017
TI  - Clinical and functional outcomes after 2 years in the early detection and
      intervention for the prevention of psychosis multisite effectiveness trial.
AB  - OBJECTIVE: To test effectiveness of the Early Detection, Intervention, and
      Prevention of Psychosis Program in preventing the onset of severe psychosis and
      improving functioning in a national sample of at-risk youth. METHODS: In a risk
      based allocation study design, 337 youth (age 12-25) at risk of psychosis were
      assigned to treatment groups based on severity of positive symptoms. Those at
      clinically higher risk (CHR) or having an early first episode of psychosis (EFEP)
      were assigned to receive Family-aided Assertive Community Treatment (FACT); those
      at clinically lower risk (CLR) were assigned to receive community care. Between
      groups differences on outcome variables were adjusted statistically according to
      regression-discontinuity procedures and evaluated using the Global Test Procedure
      that combined all symptom and functional measures. RESULTS: A total of 337 young
      people (mean age: 16.6) were assigned to the treatment group (CHR + EFEP, n =
      250) or comparison group (CLR, n = 87). On the primary variable, positive
      symptoms, after 2 years FACT, were superior to community care (2 df, p < .0001)
      for both CHR (p = .0034) and EFEP (p < .0001) subgroups. Rates of conversion
      (6.3% CHR vs 2.3% CLR) and first negative event (25% CHR vs 22% CLR) were low but
      did not differ. FACT was superior in the Global Test (p = .0007; p = .024 for CHR
      and p = .0002 for EFEP, vs CLR) and in improvement in participation in work and
      school (p = .025). CONCLUSION: FACT is effective in improving positive, negative,
      disorganized and general symptoms, Global Assessment of Functioning, work and
      school participation and global outcome in youth at risk for, or experiencing
      very early, psychosis.

PMID- 25065020
TI  - Implementing the Affordable Care Act: state action to reform the individual
      health insurance market.
AB  - The Affordable Care Act contains numerous consumer protections designed to remedy
      shortcomings in the availability, affordability, adequacy, and transparency of
      individual market insurance. However, because states remain the primary
      regulators of health insurance and have considerable flexibility over
      implementation of the law, consumers are likely to experience some of the new
      protections differently, depending on where they live. This brief explores how
      federal reforms are shaping standards for individual insurance and exam-ines
      specific areas in which states have flexibility when implementing the new
      protections. We find that consumers nationwide will enjoy improved protections in
      each area targeted by the reforms. Further, some states already have embraced the
      opportunity to customize their markets by implementing consumer protec-tions that
      exceed minimum federal requirements. States likely will continue to adjust their
      market rules as policymakers gain a greater understanding of how reform is
      working for consumers.

PMID- 25065021
TI  - A state policy framework for integrating health and social services.
AB  - Recognizing that health is determined by a variety of interrelated factors,
      states are looking to connect health care, public health, and social services to
      help achieve improved population health, better care, and reduced cost of care.
      This issue brief describes three essential components for integrating health,
      including physical and behavioral health services and public health, and social
      services: (1) a coordinating mechanism, (2) quality measurement and data-sharing
      tools, and (3) aligned financing and payment. It also presents a five-step policy
      framework to help states move beyond isolated pilot efforts and establish the
      infrastructure necessary to support ongoing integration of health and social
      services, particularly for Medicaid beneficiaries.

PMID- 25065023
TI  - Joseph Roger. 1918-2012.

PMID- 25065024
TI  - Clinical aspects of cytochrome P4502E1 (CYP2E1) which is a potent source of
      oxidative stress. Preface.

PMID- 25065025
TI  - [Q & A. A young man with prolonged vomiting symptoms].

PMID- 25065028
TI  - The emergence of Psychogenic Mode #7: emotionally literate. An addition to
      deMause's psychogenic theory of history.

PMID- 25065029
TI  - Freud as a philosopher of history.

PMID- 25065031
TI  - An outlook on the future of medical research in Europe and data protection: grim
      or prosperous?

PMID- 25065032
TI  - Medical confidentiality and patient safety: reporting procedures.
AB  - Medical confidentiality is of individual and of general interest. Medical
      confidentiality is not absolute. European countries differ in their legislative
      approaches of consent for data-sharing and lawful breaches of medical
      confidentiality. An increase of interference by the legislator with medical
      confidentiality is noticeable. In The Netherlands for instance this takes the
      form of new mandatory duties to report resp. of legislation providing for a
      release of medical confidentiality in specific situations, often under the
      condition that reporting takes place on the basis of a professional code that
      includes elements imposed by the legislator (e.g. (suspicion of) child abuse,
      domestic violence). Legislative interference must not result in the patient
      loosing trust in healthcare. To avoid erosion of medical confidentiality,
      (comparative) effectiveness studies and privacy impact assessments are necessary
      (European and national level). Medical confidentiality should be a subject of
      permanent education of health personnel.

PMID- 25065033
TI  - Data protection and the patient's right to safety.
AB  - The article investigates the issue of knowing whether or not the proposal for a
      general data protection regulation could improve the patient's safety. This has
      been analyzed through the four main contributions that should be expected at
      least from data protection to the patient's safety. In our view, data protection
      should help supporting efficient information systems in healthcare, increasing
      data quality, strengthening the patient's rights and drawing the legal framework
      for performing quality control procedures. Compared to the current legal
      framework, it is not sure that the proposal might improve any of these
      contributions to the patient's safety.

PMID- 25065035
TI  - European Court of Human Rights. ECHR 2014/8 Case of Valeriy Fuklev v. Ukraine, 16
      January 2014, no. 6318/03 (Fifth section).

PMID- 25065034
TI  - The promotion of data sharing in pharmacoepidemiology.
AB  - This article addresses the role of pharmacoepidemiology in patient safety and the
      crucial role of data sharing in ensuring that such activities occur. Against the
      backdrop of proposed reforms of European data protection legislation, it
      considers whether the current legislative landscape adequately facilitates this
      essential data sharing. It is argued that rather than maximising and promoting
      the benefits of such activities by facilitating data sharing, current and
      proposed legislative landscapes hamper these vital activities. The article posits
      that current and proposed data protection approaches to pharmacoepidemiology--and
      more broadly, re-uses of data--should be reoriented towards enabling these
      important safety enhancing activities. Two potential solutions are offered: 1) a
      dedicated working party on data reuse for health research and 2) the introduction
      of new, dedicated legislation.

PMID- 25065036
TI  - European Court of Human Rights. ECHR 2014/9 Case of Shchiborshch and Kuzmina v.
      Russia, 16 January 2014, no. 5269/08 (First Section).

PMID- 25065037
TI  - European Court of Human Rights. ECHR 2014/10 Case of Placi v. Italy, 5 December
      2013, no. 48754/11 (Second Section).

PMID- 25065038
TI  - European Court of Human Rights. ECHR 2014/11 Case of Gheorghe Predescu v.
      Rumania, 25 February 2014, no. 19696/10 (Third Section).

PMID- 25065039
TI  - European Court of Human Rights. ECHR 2014/12 Case of Koroviny v. Russia, 27
      February 2014, no. 31974/11 (First Section).

PMID- 25065040
TI  - European Court of Justice. ECJ 2014/5 Klinikum Dortmund gGmbH and Finanzamt
      Dortmund-West, 13 March 2014 (C-366/12).

PMID- 25065041
TI  - European Court of Justice. ECJ 2014/6 Octapharma France SAS v. Agence Nationale
      de Securite du Medicament et des Produits de Sante (ANSM), Ministere des Affaires
      Sociales et de la Sante, 13 March 2014 (C-512/12).

PMID- 25065043
TI  - [Epidemiologic descriptive study of the clinical characteristics of acute
      bronchiolitis in patients hospitalized at the pediatric unit of the Manati
      Medical Center Hospital].
AB  - Acute respiratory infections are the main reason for pediatric visits both to
      physician's offices and emergency departments. Bronchiolitis is an acute viral
      respiratory disease that affects about 10% of infants each year and mostly those
      under age two. The aim of this study was to identify demographic, epidemiological
      characteristics and risk factors associated with cases of bronchiolitis admitted
      to the Manati Medical Center (MMC). In addition, we tried to establish the basis
      for the development of strategies to prevent of hospitalizations and
      complications in our Institution. A retrospective descriptive study was conducted
      in the pediatric wing of MMC in Manati, Puerto Rico between January and December
      2009. A total of 508 children were included, 58 % of them male. The average age
      and weight were 12 +/- 5.3 months and 8.1 +/- 1.4 kg, respectively. We observed a
      higher predisposition among males as well as a statistically significant
      relationship between breastfeeding and protection from the disease. No
      relationship was observed between preterm birth and the parents' smoking habit
      and the development of the disease. However, the latter factor influences the
      length of hospital stay. The risk of bronchiolitis was seasonal with a peak
      between October and November. The presence of respiratory syncitial virus was
      confirmed in 67 % of the cases.

PMID- 25065044
TI  - Anemia management among hemodyalisis patients at the University Hospital in
      Puerto Rico.
AB  - End-stage renal disease is frequently complicated with anemia. Iron deficiency
      anemia occurs in most hemodialysis patients secondary to increased iron demand
      driven by the accelerated erythropoiesis that occurs when stimulating agents are
      administered as treatment of the anemia. The purpose of this study was to
      determine the prevalence of anemia and iron stores in patients undergoing
      hemodialysis at our unit; identify their treatment and effectiveness. Medical
      records of fifty-three patients undergoing ambulatory hemodialysis were evaluated
      for three months. Patient's hemoglobin, ferritin, iron, total iron binding
      capacity and percent transferrin saturation were recorded. 91% patients had
      arterial hypertension and 62% were diabetic. The prevalence of anemia was 34%,
      57% and 47% during the three-month period respectively. Only 21% of the
      population had transferrin saturation less than 20% and none had ferritin below
      200 ng/ml. Throughout the study, the majority of patients were managed with
      combination of iron and erythropoietin stimulating agents (ESAs). The prevalence
      of anemia remained elevated despite treatment with iron and ESAs. However, 56% of
      anemic patients throughout the three months showed an increase in hemoglobin
      levels by the end of the observation period. 53% of patients were treated with
      iron alone or with ESAs for the three consecutive month periods and only two had
      transferrin saturation less than 20%. In our population, ESAs low responsiveness
      is not related to iron deficiency but to the morbidity of their disease.

PMID- 25065045
TI  - Role of Helicobacter pylori infection in Hispanic patients with anemia.
AB  - Pernicious anemia represents the final phase of a process that begins with
      Helicobacter pylori-associated gastritis and evolves through progressive levels
      of atrophy until loss of parietal cell mass. Numerous studies have suggested an
      association between H. pylori infection, unexplained iron deficiency anemia and
      cobalamin deficiency. Our research question was to determine whether there is an
      association between with H. pylori infection and development of anemia in
      Hispanic patients. This cross sectional pilot study involved data analysis of
      individual from years 2010-2012 examining the association between H. pylori
      infection and hemoglobin levels in patients with Hispanic ethnicity. A total of
      189 records were evaluated, of which 33 fulfilled the inclusion criteria. The
      study sample was divided in two groups. Group-A: 5 subjects with H. pylori
      infection and anemia; Group-B: 28 patients with H. pylori without anemia. Fisher
      exact test applied between categorical variables to determine the statistical
      significance of symptoms comparing anemic vs. non-anemic H. pylori infected
      patients yielded a p = 0.0027. In addition, restoration of anemia in two subjects
      following eradication therapy without previous iron or cobalamin replacement
      therapy suggested a potential role of this bacterium in the development of anemia
      in Hispanics. In conclusion, from the results of this study a potential
      association between Helicobacter pylori infection and anemia in Hispanic patients
      is suggested. Restoration of hemoglobin after eradication of bacteria further
      supports this concept.

PMID- 25065046
TI  - Eptifibatide: gender related complications in a Hispanic population.
AB  - One of the most common indications of Eptifibatide, a GP IIb/IIIa inhibitor, is
      non-ST segment elevation myocardial infarction (NSTEMI) due to its great
      antiplatelet activity. The aim of this study was to find out if there are gender
      discrepancies when comparing complications in Hispanics treated th Eptifibatide.
      METHODS: A cross-sectional study. 116 medical records with diagnosis ofNSTEMI
      managed with Eptifibatide during 2010-2012 were included. Bleeding,
      thrombocytopenia, new ischemia, anemia and death were variables compared.
      RESULTS: The most common complication was death. There were four cases of
      bleeding, all of them occurred in the female gender, reaching a statistically
      significant difference compared to male gender (p = 0.0173); 8% of patients had
      thrombocytopenia; 9% had new ischemia during hospitalization; 13% died; 19% of
      patients developed anemia including the four cases of bleeding. CONCLUSION:
      Bleeding occurred only in women, and this difference was statistically
      significant when compared to males. More studies emphasizing the differences in
      Eptifibatide complications by gender are needed. Furthermore, it would be
      important to compare these results to non-Hispanic women. The difference found in
      the other complications analyzed was not statistically significant.

PMID- 25065047
TI  - Cephalic tetanus following penetrating eye trauma: a case report.
AB  - Tetanus is a potentially life-threatening infection characterized by muscle
      spasms. Cephalic tetanus is limited to muscles and nerves in the head and can
      occur after trauma to this area. Because of the rarity of cephalic tetanus
      clinicians may be unfamiliar with the clinical presentation unsuspecting of the
      diagnosis.

PMID- 25065048
TI  - Ocular manifestations of acute graft versus host disease after allogeneic bone
      marrow transplant.
AB  - A 17-year-old-male with Sickle Cell Disease underwent allogenic bone marrow
      transplant. Two years after the transplant the patient developed violaceous
      lichenoid papules coalescing into plaques over the face and upper extremities
      complaining of decrease visual acuity, foreign body sensation, and eye pain. A
      slit lamp examination showed injected conjunctiva, superficial I punctate
      keratopathy and decreased baseline Schirmmer test. Dermatologic evaluation and
      biopsy demonstrated chronic graft versus host disease along with the diagnosis of
      secondary keratoconjunctivitis sicca.

PMID- 25065049
TI  - Chronic eosinophilic leukemia: a rare cause of hypereosinophilic syndrome.
AB  - Hypereosinophilic syndromes are a wide group of entities. We present a 24-year
      old-male with left lower quadrant abdominal pain, elevated eosinophil counts and
      splenomegaly. Molecular analysis was positive for FIP1LI -PDGFRA gene compatible
      with chronic eosinophilic leukemia. He was managed with Imatinib producing
      resolution of the disease.

PMID- 25065050
TI  - Vitiligo, jaundice and cholestasis in a middle aged woman: a case report.
AB  - Primary biliary cirrhosis with autoimmune hepatitis (PCB/AIH) overlap is
      characterized by uncertain behavior and no standardized treatment. A 35 year-old
      woman with vitiligo, jaundice and cholestasis fulfilled serological, biochemical
      and histological criteria for PBC/AIH overlap. Treatment was initiated with
      conventional doses of corticosteroid and ursodeoxycholic acid. Her condition
      worsened with poor biochemical hepatic response. The course of action was altered
      to institute high doses of ursodiol, azathioprine and corticosteroids for
      extended periods of time. This case illustrates how increased understanding of
      the overlap PBC/AIH leads to new interventions. Recognition of these variant
      forms is critical for institutional management of both disease entities.

PMID- 25065051
TI  - Bilateral large palpable cervical masses: not always a malignant or infectious
      process.
AB  - Madelung's disease is an extremely rare disorder of unknown etiology
      characterized by multiple, non-encapsulated, infiltrative lipomas located
      symmetrically on the trunk, neck, and proximal parts of the limbs. Approximately
      200 patients have been reported in the medical literature. In this case report we
      present an extremely unusual case of multiple symmetric lipomatosis compatible
      with Madelung's disease.

PMID- 25065052
TI  - Primary clear cell carcinoma of the lung with salivary gland type features.
AB  - Clear cell carcinoma of the lung is very rare, with few cases reported in the
      medical literature. Review of case studies show that these tumors have
      significant variation in clinical outcome, including metastatic disease. We
      present a very unusual case of primary clear cell lung carcinoma of salivary
      gland type.

PMID- 25065053
TI  - Adenocarcinoma in the ileostomy of a patient with long-standing ulcerative
      colitis: a case report and review of the literature.
AB  - Primary adenocarcinoma in a permanent ileostomy carries a poor prognosis from
      other gastrointestinal malignancies. Surveillance and identification of patient
      at risk for ileostomy malignancies is a challenging problem. There are not
      reliable biological markers. The clinical evaluation, suspicion of the disease,
      common presenting symptoms including difficulty fitting the stomal appliance,
      bowel obstruction, and a friable mass should be considered as part of the
      evaluation and screening in a long standing terminal ileostomy. Biopsy of newly
      developed lesions in the periostomal area is recommended for diagnosis and
      treatment. This is a case of a primary adenocarcinoma in an ileostomy forty years
      after total colectomy for ulcerative colitis.

PMID- 25065054
TI  - [Multimodal monitoring in severe craniocerebral trauma: state the art].
AB  - Traumatic brain injury is a public health problem and leading cause of death. In
      the context of a severe head injury, monitoring strategies give us the option to
      analyze the posterior intracranial alterations to the primary lesion.
      Neuromonitoring allows us to identify the deterioration of neurological function
      and the presence of secondary brain injury that may benefit from a therapeutic
      intervention letting us know pathophysiological changes that occur in a patient
      with brain injury. Understanding the physiological data allow to individualize
      therapies and interpret variables that ultimately help us choice a better
      treatment.

PMID- 25065055
TI  - [Blood derivatives in Puerto Rico: History of the transfusion services and
      estimate of the consumption of blood units].
AB  - Puerto Rico has eight hospital blood banks and three community blood banks for a
      population around four million. The Red Cross has been in existence in Puerto
      Rico since 1893 under the Spanish Governance but it was not until 1907 which
      became the American Red Cross (ARC). Since then it has been serving Puerto Rico
      and the U.S. Virgin Islands. About 171.222 blood components, which 45% are of the
      ARC, are used. There are a number of variations in utilization and a number of
      factors that are influencing us at the national and local level and that is why
      collaboration is required in the management plan of blood components at each
      hospital and implementation of maximum units required for each case of surgery.

PMID- 25065056
TI  - The responsibility and accountability of being a registered nurse.

PMID- 25065057
TI  - Bullying and workplace violence.

PMID- 25065058
TI  - The authority for certain clinical tasks performed by unlicensed patient care
      technicians and LPNs/LVNs in the hemodialysis setting: a review.
AB  - The growing incidence of end stage renal disease (ESRD) has resulted in an ever
      increasing demand for hemodialysis services throughout the country. Unlicensed
      assistive personnel (UAP), including dialysis technicians or patient care
      technicians (PCTs), and licensed practical nurses (LPNs) or licensed vocational
      nurses (LVNs) perform a vital role in the care of patients undergoing
      hemodialysis and are a critical staff component in hemodialysis facilities. This
      analysis provides a broad overview of the positions of states with respect to the
      administration of heparin and saline via peripheral and central lines by PCTs and
      LPNs/LVNs in the hemodialysis setting.

PMID- 25065059
TI  - Strategies for removing fluids during hemodialysis.
AB  - Dry weight has most frequently been defined by the patient becoming symptomatic
      when fluid removal is attempted Hypervolemia and fluid removal require ongoing
      evaluation and the use of a number of strategies. This article reviews strategies
      for removing fluid during hemodialysis, hemodynamics of fluid removal, and
      interventions associated with the strategies for fluid removal.

PMID- 25065060
TI  - Perceived status of patient care technician training and certification impact in
      U.S. hemodialysis facilities.
AB  - In 2008, the Centers for Medicare and Medicaid Services (CMS) enacted a
      requirement for the mandatory certification of non-licensed hemodialysis patient
      care technicians (PCTs) effective in 2010. This study examined the perceived
      status of PCT training and the impact of the mandatory certification on patient
      care. Results indicated that there are differences between the current and ideal
      elements of PCT training programs; the use of electronic education materials and
      online education courses and programs is limited, and infection control
      practices, vascular access care, and patient safety are the most needed areas for
      future PCT education. Respondents were mixed in their perceptions of the impact
      certification has had on patient care.

PMID- 25065061
TI  - Isothermal dialysis to control intradialytic hypotension and patient comfort: a
      pilot study.
AB  - Isothermal hemodialysis to improve intradialytic tolerance in hypotension-prone
      patients has been effective in outpatient settings. The purpose of this pilot
      study was to examine thermal control in an acute care setting and describe
      comfort issues associated with thermal control Although complaints of cold or
      shivering occurred more frequently with the isothermal hemodialysis group, cold
      discomfort was managed by nursing interventions and was not a cause of
      significant discomfort. No statistically significant difference was observed in
      blood pressure or patient's comfort level between standard and isothermal
      dialysis. However, isothermal hemodialysis may be an appropriate hemodialysis
      option for control of intradialytic hypotension in the acute care setting.
      Further research is recommended.

PMID- 25065062
TI  - Vascular access team collaboration to decrease catheter rates in patients on
      hemodialysis: utilization of Kotter's change process.
AB  - Long-term central venous catheter (CVC) use among patients on hemodialysis
      increases the risk of infection, morbidity, and mortality. This article describes
      the use of Kotter's process of change to establish a multidisciplinary vascular
      access team to facilitate the replacement of CVCs with long-term accesses.
      Through the implementation of vascular access teams and the execution of Kotter's
      eight-step process for leading change, hemodialysis clinics will have the tools
      needed to reduce CVC utilization rates and improve patient healthcare outcomes.

PMID- 25065063
TI  - Understanding the life experience of people on hemodialysis: adherence to
      treatment and quality of life.
AB  - This hermeneutic-phenomenological study explores the lived experiences of
      patients on hemodialysis in regard to the adherence to treatment and quality of
      life. Fifteen patients were interviewed, including six women and nine men from
      three dialysis centers in Chile. Two main themes derived from the analysis: 1)
      embracing the disease and dialysis, and 2) preventing progression of the disease
      through treatment management. The findings suggest that patients recognize
      adherence to treatment and quality of life as conditions that derive from self
      care and environmental conditions, which the healthcare provider must constantly
      assess for care planning to improve the adherence and quality of life in this
      population.

PMID- 25065064
TI  - Transition and interprofessional collaboration in moving from pediatric to adult
      renal care.

PMID- 25065065
TI  - Hemodialysis catheter outcomes pilot study.

PMID- 25065066
TI  - Racial disparities in hypertension awareness and management: are there
      differences among African Americans and Whites living under similar social
      conditions?
AB  - OBJECTIVE: To examine the nature of disparities in hypertension awareness,
      treatment, and control within a sample of Whites and African Americans living in
      the same social context and with access to the same health care environment.
      DESIGN: Cross-sectional study SETTING: Southwest Baltimore, Maryland
      PARTICIPANTS: 949 hypertensive African American and White adults in the Exploring
      Health Disparities in Integrated Communities-Southwest Baltimore (EHDIC-SWB)
      Study. MAIN OUTCOME MEASURES: Hypertensive participants who reported having been
      diagnosed by a doctor were considered to be aware of their hypertension. Among
      hypertensive adults aware of their condition, those who reported taking
      antihypertensive medications were classified as being in treatment. Among the
      treated hypertensive adults who had diabetes, those with systolic BP < 130 mm Hg
      and diastolic BP < 80 mm Hg were considered to be controlled. Among the treated
      hypertensive participants who did not have diabetes, those with systolic BP < 140
      mmHg and diastolic BP < 90 mm Hg were also considered to be controlled. RESULTS:
      After adjusting for age, sex, marital status, education, income, health
      insurance, weight status, smoking status, drinking status, physical activity,
      cardiovascular disease, stroke, and diabetes, African Americans had greater odds
      of being aware of their hypertension than Whites (odds ratio = 1.44; 95%
      confidence interval 1.04, 2.01). However, African Americans and Whites had
      similar odds of being treated for hypertension, and having their hypertension
      under control. CONCLUSION: Within this racially integrated sample of hypertensive
      adults who share similar health care markets, race differences in treatment and
      control of hypertension were eliminated. Accounting for the social context should
      be considered in public health interventions to increase hypertension awareness
      and management.

PMID- 25065067
TI  - Ethnicity and health literacy: a survey on hypertension knowledge among Canadian
      ethnic populations.
AB  - OBJECTIVES: With an increase and diversity in ethnic populations in Westernized
      countries, understanding the differences in levels of knowledge surrounding
      hypertension is important in planning appropriate prevention strategies. The
      purpose of our study was to assess levels of hypertension knowledge in Chinese,
      Indian and White populations in a large metropolitan Canadian city. DESIGN: A
      telephone survey was conducted in English, Chinese (Cantonese and Mandarin) and
      Indian languages (Hindi, Punjabi and Urdu). Hypertension knowledge was assessed
      through a 10-item validated instrument; respondents received 1 point for each
      correct answer. Logistic regression was used to test differences in hypertension
      knowledge among these three populations. RESULTS: Survey response rates were
      68.7% (301) for Chinese, 61.3% (248) for Indian and 69.7% (254) for White
      populations. The average hypertension knowledge score for Chinese respondents was
      7.23 out of 10, 7.11 for Indian respondents and 7.28 for White respondents.
      Compared to White respondents, Chinese respondents were less likely than White
      respondents to know high blood pressure can cause heart attacks (adjusted odds
      ratio [aOR]: .43, 95% confidence interval [CI]: .19-.96] and Indian respondents
      were less likely to know losing weight usually decreases blood pressure (aOR:
      .38, 95% CI: .21-.68). CONCLUSIONS: Hypertension knowledge levels among these
      three ethnic/racial populations were similar and relatively high and varied by
      content. Low levels of knowledge for Chinese and Indian ethnic populations were
      on hypertension risk factors, long-term consequences of hypertension and anti
      hypertensive medication adherence. Specifically, females, recent immigrants to
      Canada and Chinese seniors were identified as sub-groups who should be targeted
      for hypertension knowledge promotion.

PMID- 25065068
TI  - Racial/ethnic differences in pregnancy-related hypertensive disease in
      nulliparous women.
AB  - OBJECTIVE: Hypertension and cardiovascular disease rates vary by race/ethnicity
      in nonpregnant adults. We aimed to examine racial/ethnic differences in
      prevalence and severity of hypertensive diseases during pregnancy in nulliparous
      women. DESIGN, SETTING, PARTICIPANTS: Nulliparous women with singleton deliveries
      and electronic medical record data on demographics and pregnancy outcomes (n =
      56,617) were selected from the Consortium on Safe Labor (2002-2008).
      Multivariable logistic regression was performed to calculate the adjusted odds of
      gestational hypertension, mild preeclampsia, severe preeclampsia, eclampsia,
      chronic hypertension, superimposed preeclampsia, and unspecified hypertension for
      women who were non-Hispanic Black, Hispanic, Asian/Pacific Islander, and
      multiracial/other race/ethnicity, compared with non-Hispanic White women.
      RESULTS: Non-Hispanic Black women had higher odds of entering pregnancy with
      chronic hypertension (adjusted odds ratio (AOR) = 1.43, 95% confidence interval
      (CI) 1.11-1.84) and had higher odds of developing mild (AOR = 1.26, 95% Cl 1.10
      1.45), severe (AOR = 1.31, 95% Cl 1.10-1.57) or superimposed preeclampsia (AOR =
      1.98, 95% ClI 1.40-2.80) compared to non-Hispanic White women. Hispanic women and
      Asian/Pacific Islanders had higher odds of remaining normotensive (AOR = 1.22,
      95% CI 1.12-1.33 and AOR=1.55, 95% CI 1.31-1.84, respectively). Conclusions: Odds
      for specific gestational hypertensive diseases varied by race/ethnicity among
      women during their first pregnancy. Non-Hispanic Black women experienced more
      severe disease, while Hispanic women and Asian/Pacific Islanders had an overall
      decreased risk compared to non-Hispanic Whites. Patterns of racial/ethnic
      variation associated with hypertensive diseases during pregnancy were similar to
      racial/ethnic associations reported for adult-onset cardiovascular disease,
      suggesting that there may be common pathways and shared risk factors.

PMID- 25065069
TI  - Research participants' opinions on genetic research and reasons for
      participation: a Jackson Heart Study focus group analysis.
AB  - The Jackson Heart Study (JHS) convened focus groups to engage the community in
      dialogue on participation in the National, Heart, Lung and Blood Institute's
      Candidate Gene Resource (CARe) project. CARe, a genome wide association and
      candidate gene study, required the release of participant phenotypic and
      genotypic data with storage at NIH for widespread distribution to qualified
      researchers. The authors wanted to assess the willingness of an African American
      community to participate in the genetics research, given the past history of
      bioethical misconduct in ethnic minority communities. The discussion produced the
      following specific issues of interest: reasons for participants' interest in
      genetics research; participants' knowledge about the JHS; and participants'
      knowledge about genetics research and its advantages and disadvantages. Training
      on genetic issues was also developed for the JHS community and staff.

PMID- 25065070
TI  - Commentary: clinician and researcher contributions to disparities in racial and
      ethnic minority participation in human subjects research.
AB  - Despite efforts focused on outreach to minority populations, the literature
      reveals that the problem of disparities in minority involvement in clinical
      research persists. Thus, the objective of this article was to present an overview
      of the barriers to engage minorities in human subject research and the
      identification of promising strategies for their recruitment and retention. I
      identified a need for an innovative approach, which would focus recruitment
      efforts primarily on clinicians and researchers who contribute their own barriers
      to the process of recruitment and retention. In this way, the most common
      outreach efforts, which specifically focus on targeted minority groups, would be
      replaced. The inclusion of minorities in clinical research is an important
      bioethical issue, particularly when considering drug pharmacokinetics and
      pharmacodynamics, which may vary widely among different racial and ethnic
      populations. In conclusion, patient barriers to participation in clinical
      research are well-documented and remain of great importance; however, clinician
      and researcher barriers, equally as important, continue to be overlooked.
      Focusing on clinicians and researchers is needed to help increase their awareness
      about the barriers to minority participation that they may present. Continued
      research and efforts are needed to understand how best to identify, address, and
      overcome these barriers.

PMID- 25065071
TI  - A comparison of psychosocial health in North American and Chinese Canadian
      cardiac outpatients, and ethnocultural correlates of quality of life.
AB  - OBJECTIVES: To: 1) compare sociodemographic, clinical and psychosocial
      characteristics of Chinese Canadian and North American cardiac outpatients, 2)
      describe the ethnocultural characteristics of Chinese Canadian cardiac
      outpatients, and 3) investigate ethnocultural correlates of quality of life among
      Chinese Canadian cardiac outpatients. DESIGN: Cross-sectional. SETTING: 11
      hospitals and two outpatient clinics of a Chinese Canadian cardiologist in
      Ontario, Canada. PARTICIPANTS: 1404 (n = 96; 6.8% Chinese Canadian) cardiac
      outpatients. MAIN OUTCOMES MEASURES: Participants completed a survey assessing
      sociodemographic, ethnocultural and psychosocial characteristics. Quality of life
      was assessed with the MacNew instrument, which was translated to traditional
      Chinese character. RESULTS: Chinese Canadian cardiac outpatients were of
      significantly lower socioeconomic status, and were less likely to be working, had
      lower activity status, body mass index, were less likely to smoke, had better
      left ventricular function, and were less likely to have undergone bypass surgery
      than their North American counterparts. Chinese Canadians reported significantly
      lower quality of life and social support than North Americans. Of the Chinese
      Canadian participants, 13 (26.5%) felt they needed an interpreter during a
      cardiac medical visit but did not receive this service. Correlates of greater
      quality of life in Chinese Canadian cardiac outpatients were greater proficiency
      in both English and Chinese languages, as well as perceived ability to
      communicate with Canadians, to fit into social situations, and understand English
      jokes. CONCLUSION: Some characteristics of Chinese Canadian cardiac outpatients
      may put their health at a disadvantage when compared to their North American
      counterparts, however some protective factors were also observed. Language
      proficiency was a key correlate of quality of life.

PMID- 25065073
TI  - Cardiovascular risks in Kazakh population in Xinjiang Province of China.
AB  - AIM: Assess the cardiovascular risks in Kazakh population in Ili of Xinjiang
      Province. METHODS: A total of 1126 participants (M/F: 443/683) aged > or = 35
      years, living in Ili for more than five years were selected via stratified random
      sampling. Fasting plasma glucose (FPG), blood lipids, body mass index (BMI), and
      blood pressure (BP) were measured. The risk was evaluated by 10-year risk
      estimation of ischemic cardiovascular disease (ICVD) in Chinese. RESULTS: The
      mean values of systolic blood pressure (SBP), body mass index (BMI), blood lipids
      were significantly higher in male than female (P < .01). The mean value (%) of 10
      year morbid risk was higher in males than females aged < 50 years (P < .05). A 10
      year absolute risk of ICVD was < 10% (P = .536) in 94.8% of males and 95.6% of
      females. The ratio of high-risk population (20%-40%) was higher in males than
      females (2.93% vs .73%, P = .004). There was significant difference in SBP, total
      cholesterol, and BMI among high, moderate, and low risk groups (P < .05).
      CONCLUSION: Our study shows a high prevalence of cardiometabolic risks in the
      Kazakh population. Immediate short-term and sustainable long-term programs should
      be carried out to prevent the morbidity caused by known preventable risk factors.

PMID- 25065072
TI  - Analysis of risk factors of acute ischemic stroke for different ethnic groups in
      Changde.
AB  - OBJECTIVES: The aim of our study was to explore the risk factors of acute
      ischemic stroke (AIS) for different ethnic groups in Changde city (a multi-ethnic
      residence inhabited mainly by Han and Tujia), Hunan Province, China. DESIGN,
      SETTING AND PARTICIPANTS: A multicenter study was performed and the demography
      data, etiology data and clinical features of 5338 AIS patients from 17 hospitals
      in Changde city were collected from January 2011 through December 2011. MAIN
      MEASURES: Student's t-test and Chi2-test were used to compare the differences
      between the Han and Tujia ethnic group in the AIS. RESULTS: In Changde, the
      incidence of AIS in the Tujia ethnic group was higher than that in the Han ethnic
      group (233.14 per million vs. 84.38 million, respectively). We found
      statistically significant differences between the Tujia and Han ethnicities in
      demographic, etiology and clinical data (eg, sex, living environment, diet,
      smoking, payment methods, cerebral hemorrhage and transient ischemic attack [P <
      .05]). In addition, compared with the Han population, the Tujia patients had a
      higher rate of the incidence of the anterior circulation infarction, partial
      anterior circulation infarction, lacunar infarction and cerebral hemorrhage.
      CONCLUSIONS: Our results indicate that lifestyle choices (eg, diet, smoking
      cigarettes), location, family heritage, and sex are associated with AIS and is
      useful for informing AIS rates and treatment for AIS.

PMID- 25065074
TI  - Health-related quality of life in obese and overweight, treatment-seeking youth.
AB  - OBJECTIVE: This study evaluated health related quality of life (HRQOL) in obese
      children using obesity-specific HRQOL measures and examined potential race and
      sex differences. PARTICIPANTS: Two-hundred and four children aged 5.03 to 13.48
      years (mean +/- SD = 10.18 +/- 1.95) and their parents participated. METHODS: All
      participants enrolled in a family-based weight loss intervention study. Their
      height and weight were measured before and after the intervention, and
      demographic information was collected. Participants also completed a weight
      related quality of life measure; children completed a self-report version, and
      parents completed a parent-proxy version. RESULTS: Higher child body mass index z
      scores (BMIz) were related to poorer HRQOL per parent and child report. Males
      reported higher emotional functioning than females, and for race, African
      American parents reported higher physical functioning for their children than
      Caucasian parents. No difference in total HRQOL was found for race. CONCLUSIONS:
      Childhood BMIz is inversely related to quality of life. Compared with male
      children, females have more impairment in quality of life. However, HRQOL did not
      differ by race. Also, although parent and child reports do overlap in certain
      areas, they also each provide unique information. Future researchers and
      clinicians would be wise to capture both child and parent perspectives regarding
      quality of life among obese children.

PMID- 25065075
TI  - Executive function and negative eating behaviors in severely obese African
      Americans.
AB  - OBJECTIVE: African Americans are disparately impacted by severe obesity. Low
      socioeconomic status and psychosocial risk factors help to explain this
      disparity; however, few studies have examined the role of negative eating
      behaviors or the influence of executive function on negative eating behaviors in
      this population. The objective was to examine the association between executive
      function (ie, inhibition and set shifting) and negative eating behaviors in
      severely obese African Americans. PARTICIPANTS: Forty-seven African Americans who
      met criteria for severe obesity participated. DESIGN AND SETTING: Data were
      analyzed from a cross-sectional study entitled Stress and
      Psychoneuroimmunological Factors in Renal Health and Disease. The mean age of
      participants was 45.7 years (SD = 10.8) and the mean educational attainment was
      13 years (SD = 2.1). MAIN OUTCOME MEASURES: Participants completed the Wisconsin
      Card Sorting Task, the Stroop Color-Word Test, and the Eating Behavior Patterns
      Questionnaire. RESULTS: Correlation results suggested poorer inhibition was
      associated with greater self-reported emotional eating and snacking on sweets.
      Subsequent hierarchical regression analyses confirmed the inverse relations
      between inhibition, emotional eating, and snacking on sweets, after controlling
      for age, sex, years of education, and depression. CONCLUSIONS: Reduced inhibition
      may be an important risk factor for negative eating behaviors and subsequent
      obesity in this population. Interventions aimed at increasing inhibition and self
      regulation in this at-risk group are warranted.

PMID- 25065076
TI  - Maintenance of long-term adequate levels of vitamin d lowers HbA1c in African
      American patients with type 2 diabetes.
AB  - OBJECTIVES: We examined the long-term effects of enhanced Vitamin D (VitD)
      supplementation on parameters of type 2 diabetes mellitus (T2DM): serum
      hemoglobin A1c, low density lipoprotein, high density lipoprotein, and
      triglyceride for the purpose of determining beneficial VitD levels in T2DM
      African Americans (AA). DESIGN AND METHODS: Following inclusion criteria,
      retrospective charts of patients aged > or = 30 years were reviewed. VitD
      supplementation was given to patients as part of drug regimen over a three year
      continuum. Pearson correlations were used to assess the relationship between VitD
      levels and levels of each parameter. Repeated measure analysis of variance was
      conducted to identify difference in mean levels of each parameter between years
      with VitD included as part of therapy. RESULTS: Vitamin D supplementation was
      inversely associated with HbA1c (r = -.286, P = .031). No correlation was found
      between levels of VitD and levels of LDL, HDL or TG. Hemoglobin A1c levels were
      found to be significantly different under VitD treatment between year 1 (mean
      VitD 24.75 microg/mL, mean HbA1c 9.15%, P = .000) and year 2 (mean VitD 33.84
      microg/mL, mean HbA1c 7.91%, P = .000) and between year 1 and year 3 (mean VitD
      34.46 microg/mL, mean 7.98% HbA1c P = .000). CONCLUSION: In T2DM AA, significant
      improvements in HbA1c are obtained with enhanced VitD supplementation as part of
      drug regimen over time. Our investigation provides the first known evidence of a
      relationship between enhanced VitD supplementation as part of a pre-existing
      medical regimen taken over long term and determinants of T2DM in a group of
      overweight and obese AA with T2DM.

PMID- 25065077
TI  - Efficacy of obesity indices and age in predicting diabetes: study on a
      transitional tribe of Northeast India.
AB  - OBJECTIVE: To evaluate the association between blood sugar level and obesity, and
      the interplay of socioeconomic change, and to investigate the efficacy of
      different obesity indices and age in predicting diabetes. METHODS: Cross
      sectional study was carried out among 603 adult Tangkhul Nagas of NE India.
      Anthropometric measurements, random blood sugar level, general and regional
      obesity indices were evaluated along with their information on socioeconomic and
      lifestyle factors. RESULTS: Socioeconomic change observed among the Tangkhuls
      influence the rise of overweight/obesity and blood sugar level. Obesity and
      elevated blood sugar level were highly prevalent and interrelated. Diabetes and
      obesity were also found to be associated with age. Central obesity indices were
      highly associated with blood sugar level. Odds ratio showed the likelihood of
      developing prediabetes/diabetes among centrally obese participants. Correlation
      between blood sugar level, age and obesity indices showed that waist hip ratio
      had the highest correlation with blood sugar. It implies the higher reliability
      of central obesity than general obesity or age in determining blood sugar level.
      CONCLUSION: The transition of the Tangkhul Naga tribe in terms of socioeconomic
      and lifestyle factors contributes to the escalating prevalence of
      overweight/obesity and diabetes. The rising epidemic is not restricted to highly
      urbanized societies but now has penetrated even to traditional and transitional
      tribes owing to their changing lifestyle. Different facets of the complex
      associations between obesity, age, diabetes and socioeconomic change were
      observed. Central obesity indicator, waist hip ratio emerge as the paramount
      predictors of prediabetes/diabetes.

PMID- 25065078
TI  - Effect of diabetes self-efficacy on glycemic control, medication adherence, self
      care behaviors, and quality of life in a predominantly low-income, minority
      population.
AB  - OBJECTIVE: This study examined the effect of self-efficacy on glycemic control,
      self-care behaviors, and quality of life in low-income, minority adults with
      diabetes. METHODS: Data on 378 participants were examined. Multiple linear
      regression assessed associations between self-efficacy, hemoglobin A1c,
      medication adherence, diabetes knowledge, self-care behaviors and quality of
      life. RESULTS: Self-efficacy had modest correlations with glycemic control (r = 
      .250, P < .001), medication adherence (r = -.352, P < .001), diabetes knowledge
      (r = .118, P = .039), diet (r = .420, P < .001), exercise (r = .220, P < .001),
      blood sugar testing (r = .213, P < .001), foot care (r = .121, P = .032), and
      mental health related quality of life (r = .137, P = .017). In the regression
      model, self-efficacy was significantly associated with glycemic control (3 = 
      .104, 95% CI: -.157, -.051), medication adherence (3 = -.067, 95% CI: -.090, 
      .044), diet (3 = .150, 95% CI: .108, .191), exercise (-3 = 113, 95% CI: .065,
      .161), blood sugar testing (3 = .107, 95% CI: .049, .164) and mental health
      related quality of life (3 = .112, 95% CI: .051, .173). CONCLUSION: Higher self
      efficacy was associated with improved glycemic control, medication adherence,
      self-care behavior and mental health related quality of life. PRACTICE
      IMPLICATIONS: Emphasis on self-efficacy is relevant for educational interventions
      developed for low-income, minority populations.

PMID- 25065079
TI  - Body composition and muscular strength as predictors of bone mineral density in
      African American women with metabolic syndrome.
AB  - Our cross-sectional study investigated the relationships between regional bone
      mineral density (BMD) and body composition variables, including total body lean
      mass (LM) and fat mass (FM), as well as muscular strength in overweight and obese
      African-American (AA) women with metabolic syndrome (MetS). Forty-four women
      ranging in age from 39 to 61 years participated. Upper and lower body strength
      measurements were assessed using chest press and leg extension exercises,
      respectively. Body composition and BMD of the total body, spine (L2-L4), hip, and
      radius were measured by dual-energy X-ray absorptiometry. LM was positively
      correlated with total body, spine, hip, and radius BMD (r = .338-.603, all P <
      .05), and FM was positively correlated with total body BMD (r = .343, P < .05).
      In multiple linear regression analyses after controlling for age, height, total
      energy, and calcium intake, LM was a significant positive determinant of BMD at
      various skeletal sites (P < .05), while FM was negatively related to BMD of total
      hip (P < .05). Our results indicate that LM is an independent predictor of total
      body, spine, hip, and total radius BMD. In contrast, FM is a negative predictor
      of total body and hip BMD in overweight or obese AA women with MetS (P < .05).
      Upper and lower body muscular strength measures were not associated with BMD at
      any skeletal sites. These results suggest an important role for LM in preventing
      the development of osteopenia and osteoporosis.

PMID- 25065080
TI  - Examination of race disparities in physical inactivity among adults of similar
      social context.
AB  - OBJECTIVE: The objective of the study was to determine whether race disparities
      in physical inactivity are present among urban low-income Blacks and Whites
      living in similar social context. DESIGN: This analysis included Black and White
      respondents ( > or = 18 years) from the Exploring Health Disparities in
      Integrated Communities-Southwest Baltimore (EHDIC-SWB; N=1350) Study and the
      National Health Interview Survey (NHIS; N = 67790). Respondents who reported no
      levels of moderate or vigorous physical activity, during leisure time, over a
      usual week were considered physically inactive. RESULTS: After controlling for
      confounders, Blacks had higher adjusted odds of physical inactivity compared to
      Whites in the national sample (odds ratio [OR] = 1.40; 95% confidence interval
      [CI] =1.30-1.51). In EHDIC-SWB, Blacks and Whites had a similar odds of physical
      inactivity (OR = 1.09; 95% CI .86-1.40). CONCLUSION: Social context contributes
      to our understanding of racial disparities in physical inactivity.

PMID- 25065081
TI  - The influence of sitting time and physical activity on health outcomes in public
      housing residents.
AB  - OBJECTIVES: Examine differences between levels of physical activity and sitting
      time for residents of public housing developments located in high vs low income
      neighborhoods, and whether physical activity or sitting time had a greater
      influence on health outcomes. DESIGN: Secondary data analysis from the Healthful
      Options Using Streets and Transportation in Our Neighborhoods (HOUSTON) project.
      SETTING: Public housing developments located in Houston, TX. PARTICIPANTS:
      African American, adult males and females. MAIN OUTCOME MEASURES: Self-reported
      PA and time spent sitting on weekdays were measured using the International
      Physical Activity Questionnaire (IPAQ) short form. Participants completed
      measures of BMI (kg/m2), % body fat (%BF) and resting blood pressure to assess
      health outcomes. Neighborhood income was defined as the median household income
      at the census block group level, obtained from the 2006-2010 American Community
      Survey. RESULTS: All participants (N = 216) had an annual household income of <
      or = $19,350, and neighborhood income ranged from $9,226 to $57,618. Participants
      reported an average of 4342.2 +/- 4828.3 MET-min/wk of physical activity, and 4.5
      +/- 3.2 hours of sitting per weekday. Time spent sitting was associated with BMI
      (beta = .50, t = 2.4, P = .018), %BF (beta = .87, t = 3.6, P =.000), and
      diastolic blood pressure (beta = .62, t = 2.1, P = .041). Physical activity was
      not significantly associated with any health outcomes. CONCLUSION: Our findings
      indicate that public housing residents' health statuses are vulnerable to
      sedentary behaviors regardless of the affluence of the neighborhood surrounding
      the housing development.

PMID- 25065082
TI  - Ethnicity as a predictive factor for hepatocellular carcinoma screening among
      patients in Hawaii.
AB  - OBJECTIVES: Although hepatocellular carcinoma (HCC) surveillance is associated
      with mortality reduction, it continues to be underutilized. The failure to
      conduct screening tests is a significant factor in the late diagnosis of
      hepatocellular carcinoma when curative interventions may not be feasible. Reasons
      for these low surveillance rates are unclear and need to be elucidated. DESIGN,
      SETTING, PATIENTS: This retrospective study reviewed 616 cases of HCC from a
      hepatobiliary surgery office in Hawaii for age, sex, ethnicity, birthplace,
      residence, education, employment, insurance, and obesity to determine their
      influence on HCC screening. MAIN OUTCOME MEASURES: HCC screening. RESULTS: Of the
      616 cases, only 132 patients (21.4%) had undergone screening. Although the
      majority of patients were male, those who were screened were more likely to be
      female (P = .0082). However, multivariate analysis found ethnicity to be the sole
      determinant of screening (P < .0005). Koreans were more likely than Whites to
      have had screening, whereas Japanese, Pacific Islanders, and Filipinos were less
      likely. Age > 60 years, sex, American birthplace, urban residence, high school
      completion, employment status, insurance, and BMI > 35 kg/m2 were not predictors
      of screening. CONCLUSIONS: Of the sociodemographic factors, ethnicity was
      important in predicting screening. Further research is needed to understand the
      reasons for these ethnic differences and to develop targeted interventions to
      improve hepatocellular carcinoma surveillance utilization rates.

PMID- 25065083
TI  - Race and invasive fungal infection in solid organ transplant recipients.
AB  - Health disparities in access to solid organ transplantation (SOT) and graft
      survival are well recognized, but there are limited data on the relationship of
      race to risk of invasive fungal infection (IFI) among SOT recipients. We
      conducted a case-control study using data from the Transplant-Associated
      Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases (n =
      1,214) and controls (n = 16,550) were compared on demographic variables using chi
      square, and the relationship between race and IFI was assesses with unconditional
      logistic regression. Compared to White transplant patients, Blacks had similar
      odds of developing IFI (OR = .97, 95% Cl 0.82-1.15, P = .7125), while
      participants who identified as other ethnicity were less likely to develop IFI
      (OR = .56, 95% Cl .41-.75, P < .001). Blacks, when compared to White patients,
      were at increased odds of developing cryptococcal infection (OR 2.19, 95% CI 1.35
      3.54, P = .002). Despite pharmacogenetic differences, Black transplant recipients
      were not more likely overall to develop IFI compared to White transplant
      recipients.

PMID- 25065084
TI  - Silent abnormal placentation linkage to peripartum hysterectomy: Thammasat
      University Hospital 6-year study.
AB  - OBJECTIVE: To determine the prevalence, indications, types and complications of
      peripartum hysterectomy at Thammasat University Hospital, Thailand. MATERIAL AND
      METHOD: A retrospective peripartum hysterectomy (PH) study. Data came from
      parturient who delivered at Thammasat University Hospital, Pathumthani, Thailand
      between January 2007 and December 2012. RESULTS: In the period of 6 years, there
      were 37 cases of PH among 28,023 parturient. The overall prevalence of PH was
      1.32 per 1,000 deliveries with average parturientage of 30. Nineteen
      hysterectomies were performed after vaginal delivery (1.1/1,000) and the
      remaining 18 hysterectomies were performed after cesarean section (1.67/1,000).
      Seven cases (18.9%) were performed as subtotal and the remaining 30 cases (81.1%)
      as total hysterectomy Major indication of PH was uterine atony (75.7%, 28/37)
      followed by abnormal placentation (10.8%, 4/37) and uterine rupture (5.4%, 2/37).
      From hysterectomy specimens, placenta accreta, placenta increta and placenta
      percreta were found in 5, 3, and 3 cases, respectively. Two cases of cervical
      intraepithelial neoplasia were later discovered from hysterectomy specimens.
      Three cases of placentapercreta were associated with pre-operative diagnosis of
      placenta adherent, uterine rupture and placenta previa. The average estimated
      blood loss was 2,416 ml. The overall surgical complication rate was 35.1%
      (13/37). The rate of reoperation, maternal death, wound infection, gut
      obstruction and lung complications were 16.2, 8.1, 2.7, 2.7 and 2.7 percent,
      respectively. CONCLUSION: Peripartum hysterectomy is a major hazardous procedure
      carrying a high mortality and morbidity rate. In this study, maternal mortality
      was 8.1%. Silent abnormal placentation was found in 21.2 percent (7/33) of
      hysterectomy specimen.

PMID- 25065085
TI  - The efficacy of hospital-based food program as galactogogues in early period of
      lactation.
AB  - OBJECTIVE: Galactogogue food has been frequently used among lactating women
      without reported efficacy data. The present study was aimed to address the
      outcome of hospital-based food programs as defined by the onset of lactation and
      infant's weight loss. MATERIAL AND METHOD: A Quasi-experimental design was done
      to compare the maternal breast fullness/heaviness and infants' body weight among
      106 women in galactogogue group and 127 controls. Data was gathered daily from
      the 1st day of postpartum through the date discharged regarding timing of first
      breast feeding, nursing frequency, LATCH score, nonbreast-milk fluid, breast
      fullness/hardness, leakage of colostrum/breast milk, let-down reflex and infants'
      body weight. RESULTS: Maternal report of breast fullness/heaviness within the
      first 48 hours in galactogogue group was significantly more than control (71.7%
      and 56.7%, respectively; p < 0.001). Proportion of infant who had an excessive
      weight loss, as defined by weight loss more than 7% within the first 48 hours, in
      galactogogue group was significantly lower than controls (15.1% and 24.4%,
      respectively; p = 0.043). CONCLUSION: The use of traditional food as hospital
      based food program had some efficacies in the early period of lactation,
      regarding presence of breast fullness and reduction of infant's weight loss.
      However the efficacy in maintaining breast milk production should be further
      studied. Likewise, frequent breastfeeding and thorough emptying of breasts
      definitely result in increased milk production and should be evaluated in all
      lactating women.

PMID- 25065086
TI  - The safety of propofol infusion compared to midazolam and meperidine intravenous
      bolus for patients undergoing double balloon enteroscopy.
AB  - OBJECTIVE: The double balloon enteroscopy (DBE) procedure is long and requires
      moderate sedation. We aim to determine whether the administration of propofol
      infusion is safe by comparing it to intravenous midazolam/meperidine in patients
      undergoing DBE. MATERIAL AND METHOD: A prospective study with 48 patients was
      conducted at King Chulalongkorn Hospital randomizing (block of four) patients
      into two groups. In group 1, 28 patients were enrolled for intravenous
      midazolam/meperidine, and one patient was dropped out before underwent DBE due to
      hemodynamic instability. Therefore, 27 (n = 27) participants were included in
      Group 1. In group 2, 28 patients were enrolled for propofol infusion, and seven
      patients were dropped out before underwent DBE, five due to hemodynamic
      instability (n = 5), and two refused treatment (n = 2). Therefore, 1 (n = 21)
      participants were included in Group 2. Vital signs and oxygen saturation were
      regularly monitored. RESULTS: Mean +/- SD age of patients was 56.8 +/- 9.2 years,
      and 41.7% of patients were male. There was no difference in demographic data
      between the groups. For the safety profile, 25.9% of the midazolam/meperidine
      group and 33.3% of the propofol group developed hypotension and/or desaturation
      (p = 0.45). The patients' satisfaction of group 1 and group 2 were 86.7 +/- 6.5%
      and 86.3 +/- 8.1%, respectively, and presented no significant difference (p =
      0.89). CONCLUSION: Propofol infusion is safe and shows no difference in outcome
      from the midazolam and meperidine sedation for the DBE procedure.

PMID- 25065087
TI  - Treatment outcomes of new and previously-treated smear positive pulmonary
      tuberculosis at Srinagarind Hospital, a tertiary care center in northeast
      Thailand.
AB  - OBJECTIVE: To study treatment outcomes of new and previously-treated smear
      positive pulmonary TB according to current WHO guideline 2010 and factors related
      to treatment success at Srinagarind Hospital. MATERIAL AND METHOD: Adult patients
      who had smear-positive pulmonary TB treated at Srinagarind Hospital between
      January 2005 and December 2010 were enrolled in the present study. RESULTS: Over
      a 6-years period, 322 patients (272 new and 50 previously-treated cases) were
      diagnosed smear positive pulmonary TB. The mean age was 48.85 (SD 17.9) years and
      the male to female ratio was 1.8:1. The mean duration of symptoms in the
      previously-treated group was longer than the new cases (2.39 vs. 1.99 months, p =
      0.38). Symptoms, underlying diseases, HIV status, and organ involvement between
      these two groups were not different. Two-thirds (72.1% of patients) had cough,
      35.4% had fever and 20.5% weight loss. Twenty-three percent of cases had
      underlying DM and 7.8% were HIV positive. Disseminated TB was found in 18.9% of
      cases. The mean duration of treatment in new cases was 6.88 months vs. 11.20
      months in previously-treated cases. The common regimens for new cases included
      2IRZE/4IR (72.8%) and 2IRE/7IR (19.1%) vs. 2IRZE/4IR (62%), 2IRE/7IR (12%), and
      other regimens for MDR patients (6%) among the previously-treated cases. However
      in previously-treated group IRZES/IRZE/IRE (p = 0.001), second-line drugs (p =
      0.002), and MDR regimens (p < 0.001) were statistically more common treatments
      than in the new cases group. About 60% of cases were treated at TB clinic. The
      success rate among new cases who had completed treatment at Srinagarind Hospital
      was higher than for previously-treated ones (94.8% vs. 86.4%; p = 0.04). Among
      previously-treated cases (n = 50); 24 were defaulters, 19 were relapses, and
      seven were failures. For the defaulted and relapsed cases, patients usually
      received the IRZE/IR or IRZES/IRZE/IRE regimens. On the other hand, for failure
      cases, patients usually received the second-line drugs or MDR regimens. The
      overall success rate in defaulted cases was 87.6%, vs. 68.4% who relapsed and
      57.1% who failed (p = 0.067). For new cases, the isolations found DR-TB 3.6% and
      MDR-TB 0%. For previously-treated cases, the isolations found DR-TB 16.67% and
      MDR-TB 6.25%. The only one factor related to successful outcomes was treatment at
      TB clinic (adjusted OR 2.01, 95% CI 1.18-3.43). CONCLUSION: Previously-treated
      pulmonary TB had less success rate than new cases. Culture and susceptibility for
      previously-treated group were recommended before starting treatment. Treatment at
      TB clinic improved treatment outcomes.

PMID- 25065088
TI  - Outcome analysis of jaundice fast-track system implementation in Thammasat
      University Hospital.
AB  - BACKGROUND: Infants who were readmitted with high level of bilirubin (more than
      20 mg/dl) should be treated as an acute medical emergency to prevent acute and
      chronic bilirubin encephalopathy. OBJECTIVE: To determine causes of severe
      neonatal hyperbilirubinemia, risk factors for exchange transfusion and outcomes
      of neonate after implementation of the jaundice fast-track system in Thammasat
      hospital. MATERIAL AND METHOD: The medical records of neonates presenting with
      clinically significant hyperbilirubinemia to the outpatient department or
      emergency department after implementation of the jaundice fast-track system at
      Thammasat university from October 1, 2010 through september 30, 2012, were
      retrospectively reviewed. RESULTS: There were 76 infants included in the study.
      One infant had neurological abnormalities consistent with acute bilirubin
      encephalopathy at presentation. all infants received intensive phototherapy.
      Eight infants (10.5%) underwent an exchange transfusion. a cause of
      hyperbilirubinemia was identified in 66 cases (86%). Breastfeeding jaundice was
      the most common cause (47%). The mean peak MB level was higher in the exchange
      transfusion group than the phototherapy group (25.0 +/- 2.9 mg/dl vs. 21.2 +/-
      1.8 mg/dl, p < 0.001). Three infants in the exchange transfusion group had sepsis
      on admission compared to none in the phototherapy group, (p < 0.001). Infant
      diagnosed as cephalhematoma underwent an exchange transfusion. The median (range)
      length of stay was significantly longer in the exchange transfusion group than
      the phototherapy group (9 (2-15) days vs. 2 (1-12) days, p < 0.001). There were
      no statistical differences between the two groups in age at readmission and time
      to phototherapy. All infants in this study were discharged as no neurological
      abnormalities. Infants presented with peak MB > or = 24 mg/dl had the greatest
      risk of exchange transfusion (or = 26.6; 95% ci = 4.6, 153.7). CONCLUSION:
      Initiating phototherapy within an hour of admission in infants who were
      readmitted with high levels of bilirubin is effective to prevent bilirubin
      encephalopathy. Physicians' early recognition of the risk factors to exchange
      transfusion is, therefore, crucial.

PMID- 25065089
TI  - Comparative study on the characteristics of Meckel's diverticulum removal from
      asymptomatic and symptomatic patients: 18-year experience from Thailand's largest
      university hospital.
AB  - OBJECTIVE: To report an experience with Meckel's diverticulum (MD) from a
      University Hospital in Thailand, and to compare the characteristics of MD removal
      from asymptomatic patients and symptomatic patients. MATERIAL AND METHOD: The
      authors retrospectively reviewed the medical records of patients undergoing the
      resection of MD between January 1994 and July 2011 at the Faculty of Medicine
      Siriraj Hospital, Mahidol University, Bangkok. The patients were subsequently
      divided into two groups. The asymptomatic group included individuals with MD that
      were found incidentally during the course of laparotomy performed for reasons not
      related to the complications of the MD. The symptomatic group included
      individuals presenting with complications related to the MD. Data were recorded
      including patient's demographics, clinical presentation, histopathologic
      findings, and postoperative outcomes. RESULTS: The present study included 84
      patients (53 males, 63%). Of whom, 60 patients (71%) were pediatric (age < 16
      years) and 51 patients (61%) were symptomatic. The most common presentation of
      symptomatic MDs in pediatric and adult patients was lower gastrointestinal
      bleeding and mechanical small bowel obstruction, respectively. The correct
      preoperative diagnosis of MD was made in only 20 patients (39%) of the
      symptomatic group, all with 99mTc-pertechnetate scanning. The MDs in the
      symptomatic group were significantly longer with a wider base than those in the
      asymptomatic group, 3.2 vs. 2.0 cm in length (p = 0.001) and 1.8 vs. 1.0 cm in
      width (p < 0.001). Ectopic tissue was present more significant in the symptomatic
      group than in the asymptomatic group (51% vs. 12%; p < 0.001). None of the
      resected MDs contained neoplasm. There was no significant difference in the
      morbidity or mortality rate between the symptomatic and asymptomatic groups.
      CONCLUSION: The MDs in the symptomatic patients were significantly longer with a
      wider base than those in the asymptomatic patients. Symptomatic MDs contained
      ectopic tissue more frequently than asymptomatic MDs.

PMID- 25065090
TI  - Effects of adding concentration therapy to Kegel exercise to improve continence
      after radical prostatectomy, randomized control.
AB  - OBJECTIVE: To compare the efficacy of pelvic floor muscle exercise with the
      concentration therapy versus pelvic floor muscle exercise alone after radical
      prostatectomy. MATERIAL AND METHOD: One hundred thirty five patients were
      randomized into the intervention group that concentration therapy was added to
      Kegel exercise, and control group that was Kegel exercise only, using the
      stratified randomization (stratified by taking the catheter off before and after
      discharge) and type of surgery. Incontinence was defined as a loss of urine equal
      or more than to 2 grams in one-hour pad test, before and after the test in each
      sample group. Follow-up results were obtained by phone visit at 3, 4, 5, 6, 8,
      10, and 12 weeks after surgery RESULTS: In the intervention group, 65 of 68 cases
      (95.6%) had continence in three months, compared to 48 of 67 (71.6%) in the
      control group, with significant statistical difference (p-value < 0.001). The
      secondary result was the regularity in practicing. It was 80% in total. In the
      intervention group, 66 of 68 cases (97.06%) practiced compared to 34 of 67
      (50.75%) in the control group, which was significant difference between the two
      groups. CONCLUSION: Combined concentration therapy with Kegel exercise had
      significantly improved continence after radical prostatectomy

PMID- 25065091
TI  - Outcomes of abdominal aortic aneurysm with aortic neck thrombus after
      endovascular abdominal aortic aneurysm repair.
AB  - BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR) has increasingly
      been performed for the last two decades. One of the anatomical exclusion
      criterion of EVAR is the presence of thrombus within the infrarenal neck of an
      aneurysm. OBJECTIVE: To investigate the influence of proximal aortic neck
      thrombus morphology on clinical outcomes after EVAR. MATERIAL AND METHOD: The
      subjects were retrospectively recruited from all the patients whom undergone EVAR
      in our institution between January 2010 and December 2012. The patients with
      apparent thrombus of more than 40% at proximal aortic neck were included Primary
      endpoints consisted of technical success and perioperative mortality. Secondary
      endpoints included adjuvant procedures at neck, procedural details, perioperative
      adverse events, ICU, and hospital stay. The late outcomes of stent grafts related
      complications were the presence of endoleak, aneurysm expansion, stent graft
      migration, stent graft thrombosis, AAA rupture, secondary intervention rate, and
      conversion to open repair RESULTS: Twenty-one out of 145 patients having thrombus
      of more than 40% of circumferential aortic neck underwent EVAR. The mean follow
      up was 15.4 months (range, 2-36 months). There was 100% technical success with no
      perioperative death. Adjuvant of aortic neck procedure was required in three
      patients. One patient developed graft limb occlusion. In addition, one patient
      developed renal infarction requiring long-term hemodialysis and two patients
      presented with blue toe syndrome and trash feet. During late follow-up, three,
      five, and two patients had a type II endoleak at one, six, and 12 months,
      respectively without AAA sac expansion. There was no stent graft migration, stent
      graft thrombosis, or ruptured AAA. Three patients expired during the late follow
      up. In addition, there was neither conversion to opened repair nor secondary
      intervention. CONCLUSION: The presence of aortic neck thrombus may not be a
      contraindication for EVAR in selected patients. However, it seems to negatively
      influence the outcomes in the aspect of renal and peripheral embolization, which
      could be prevented during EVAR procedure. There was no adverse graft-related
      complication, secondary intervention, or aneurysm-related mortality during mid
      term follow-up period.

PMID- 25065092
TI  - The length of small bowel in Thai patients.
AB  - OBJECTIVE: To Evaluate the length of small bowel (SB) in Thai patients. MATERIAL
      AND METHOD: The present prospective study included Thai adults who underwent
      elective open laparotomy at the Department of Surgery, Faculty of Medicine
      Siriraj Hospital between August 2011 and May 2012. Patients who had previous
      laparotomy, intra-abdominal adhesions, or gross abnormality of SB were excluded
      The length of SB was measured using an umbilical cord tape, from the duodeno
      jejunal junction to the ileo-cecal valve. RESULTS: Sixty-four patients were
      enrolled during the study period According to the exclusion criteria, only 48
      patients were eligible for study. There were 27 men and 21 women, with an average
      age of 60 years (range 28-88). The average length of SB (only jejunum and ileum)
      was 428 +/- 105 cm (range 169-745). Male adults had about 90 cm longer SB than
      female adults (468 +/- 105 cm vs. 376 +/- 81 cm; p < 0.01), particularly of the
      jejunum (179 +/- 78 cm vs. 106 +/- 38 cm; p < 0.01). The ileum accounted for
      about two-third of the total SB length. There was no association between SB
      length and age, body weight, height, or body mass index. CONCLUSION: Based on the
      present study, the total length of small bowel (jejunum and ileum) in Thai
      patients was approximately 430 cm. Male adults had significant longer SB than
      female adults, particularly the jejunal segment.

PMID- 25065093
TI  - Oral rehydration with 10% carbohydrate drink for preventing postoperative nausea
      and vomiting (PONV) after low dose of spinal morphine.
AB  - BACKGROUND: Preoperative oral carbohydrate (CHO) drink may improve patients'
      comfort. However, whether it prevents or reduces postoperative nausea and
      vomiting (PONV) is questionable. OBJECTIVE: Evaluate the effect of oral
      rehydration with 10% CHO drink before anesthesia on incidence and severity of
      postoperative nausea and vomiting (PONV) after spinal morphine injection.
      MATERIAL AND METHOD: One hundred patients scheduled for unilateral total knee
      replacement (TKR) were randomly divided into two equal groups (n = 50 each).
      Group I patients received 400 ml 10% CHO drink the preoperative night and 2-hour
      before anesthesia, whereas Group II patients served as control. Spinal anesthesia
      for all patients contained 0.5% bupivacaine 2.0 to 3.5 ml plus morphine 0.2 mg.
      Pain therapy was standardized with femoral nerve block, local infiltration,
      intravenous parecoxib, and oral paracetamol. Incidence and severity of PONV
      within 24 hours were recorded In addition, preoperative intensity of thirst and
      hunger, dry lips and throat, and anxiety was also recorded RESULTS: Incidence and
      severity of PONV (81.2% vs. 72.0%, p = 0.536) as well as preoperative thirst,
      hunger dry lips, and throat were not different between the groups. CONCLUSION:
      Preoperative oral rehydration with carbohydrate drinks had no positive effect on
      PONV nor patients' comfort.

PMID- 25065094
TI  - Precorneal tear film in pterygium eye.
AB  - BACKGROUND: Symptoms of pterygium are similar to dry eye symptoms such as dryness
      and irritation. Precorneal tear film may be changed in pterygium eye. OBJECTIVE:
      To evaluate tear breakup time and Schirmer's test results in patients with
      unilateral pterygium, and to find whether tear breakup time and Schirmer's test
      results were related to the size of pterygium. MATERIAL AND METHOD: Ninety-two
      patients, aged between 29 and 78 years, were enrolled in this study. The size of
      pterygium was measured from limbus to apex of pterygium on a horizontal axis.
      Tear breakup time and Schirmer's test results were compared in pterygium eye and
      contralateral normal eye of the same patient. The paired t-test was used for
      calculating the difference. The Pearson correlation was used to assess the
      correlations of tear breakup time and Schirmer's test with pterygium size.
      RESULTS: The mean horizontal size of pterygium +/- standard deviation was 2.1 +/-
      0.7 millimeters. The mean +/- standard deviation of tear breakup time in
      pterygium eyes was 5.5 +/- 1.9 seconds compared with 11.3 +/- 2.7 seconds in
      contralateral normal eyes (t = 23.28, p < 0.001). The mean +/- standard
      deviations of Schirmer's test results in pterygium eyes and the opposite normal
      eyes were 9.8 +/- 3.9 and 10.0 +/- 3.9 millimeters, respectively (t = 1.43, p =
      0.16). Both tear breakup time and Schirmer's test results had no correlation with
      pterygium size. The correlation coefficients between the size of pterygium and
      tear breakup time, and pterygium size and Schirmer's test results were 0.11 (p =
      0.30) and 0.03 (p = 0.77), respectively. CONCLUSION: The size of pterygium does
      not correlate with tear breakup time and Schirmer's test results. A decrease in
      tear breakup time, but normal Schirmer's test results, could be found in
      pterygium eyes.

PMID- 25065095
TI  - Benefit of double contrast MRI in diagnosis of hepatocellular carcinoma in
      patients with chronic liver diseases.
AB  - OBJECTIVE: To assess the benefit on diagnosis of hepatocellular carcinoma (HCC)
      in patients with chronic liver disease or cirrhosis with double contrast MR
      imaging compared to the routine gadolinium-based MR imaging. MATERIAL AND METHOD:
      Seventy-one consecutive patients with cirrhosis or chronic hepatitis underwent
      multiphase, gadolinium-enhanced liver MRI examination and sequentially
      superparamagnetic iron oxide (SPIO)-enhanced images. The presence signal
      intensities of lesions on non-contrast sequences, dynamic gadolinium-enhanced
      images and delayed 10-min post-SPIO T2*-weighted images were recorded. RESULTS:
      Among 27 patients, 15 HCCs from 12 patients were diagnosed by surgical (n = 7)
      and non-surgical (n = 8) proofs. The overall sensitivity, specificity, positive
      predictive value, and negative predictive value of double contrast-enhanced
      images in 12 patients were 83.3% (95% CI: 58.5, 96.2), 33.3% (95% CI: 5.4, 88.4),
      88.2% (95% CI: 63.5, 98.2), and 25% (95% CI: 4.1, 79.6) and these of gadolinium
      enhanced images were 72.2% (95% CI: 46.5, 90.2), 33.3% (95% CI: 5.4, 88.4), 86.6%
      (95% CI: 59.5, 97.9), and 16.6% (95% CI: 2.7, 63.9), respectively. There were two
      benign hepatic nodules (1 adenoma, 1 dysplastic nodule) suspected as HCCs on MR
      images and two surgically proven-HCCs, invisible on gadolinium-enhanced images,
      detected as defect on only delayed 10-min post-SPIO T2*-weighted images.
      CONCLUSION: SPIO-enhanced images in double contrast-enhanced MR imaging had an
      additional value on HCC detection, compared to gadolinium-enhanced MR imaging, in
      patients with chronic liver disease or cirrhosis.

PMID- 25065096
TI  - Outcome of ultrasound-guided small-bore catheter drainage in exudative pleural
      effusions.
AB  - OBJECTIVE: To evaluate the outcome and safety of ultrasound-guided percutaneous
      catheter drainage of exudative pleural effusion. MATERIAL AND METHOD: The present
      study was a retrospective analysis of 412 pleural effusions from 373 patients
      that underwent ultrasound-guided small-bore catheter drainage in exudative
      pleural effusions between 2004 and 2009. RESULTS: The two most common causes for
      drainage were parapneumonic effusion or empyema (52.2%) and malignant effusion
      (30.3%), while the remains were trauma, iatrogenic, and others. Overall clinical
      success rate was 76.5%. The success rate was lower among malignant pleural
      effusion (p = 0.003). Causes of effusion were the only independent predictors
      related to success. Only five (1.2%) patients developed complication during the
      procedure. Seventy-five of 412 effusions (15.8%) developed complication during
      the period of drainage; the majority were drain blockage (9%) and accidental
      dislodgment (4.1%). CONCLUSION: Ultrasound-guided small-bore catheter drainage
      was a safe and efficient procedure for exudative pleural effusions.

PMID- 25065097
TI  - Determination of asbestos bodies in bronchoalveolar lavage fluids in Thailand.
AB  - OBJECTIVE: Asbestos bodies (AB), ferroprotein-coated asbestos fiber may be
      present in bronchoalveolar lavage fluid (BALF) of asbestos exposed persons. The
      present study was conducted to evaluate the prevalence and number of asbestos
      bodies in the BALF of tenable asbestos exposed workers compare to general
      population in Thailand. MATERIAL AND METHOD: Thirty workers of cement pipe and
      roof tile factories using chrysotile asbestos and 30 unexposed patients that
      underwent diagnostic bronchoscopy were included in this study. Determination of
      asbestos bodies was made by membrane filtration method as described in earlier
      reports. RESULTS: The findings were positive in six workers and in one control
      subject (0.1-3.6 vs. 0.2 AB/ml of BALF, p = 0.449). CONCLUSION: AB was identified
      in workers more often than in pulmonary disease patient. Two of workers had more
      than 1 AB/ml of BALF.

PMID- 25065098
TI  - Prevalence of neuropsychiatric symptoms in Alzheimer's disease: a cross-sectional
      descriptive study in Thailand.
AB  - OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms in Thai
      patients with Alzheimer's disease. MATERIAL AND METHOD: The present study is a
      cross-sectional descriptive design. The participants comprised 62 patients from
      the Memory Clinic at Thammasat University Hospital, Thailand. Subjects were
      diagnosed as having Alzheimer's disease according to the National Institute of
      Neurological and Communicative Disorders and Stroke and Alzheimer's disease and
      Related Disorders Association (NINCDS-ADRDA) criteria and received global
      Clinical Dementia Rating scale (CDR) score of at least stage 1. All participants
      were assessed using the Neuropsychiatric Inventory Questionnaire (NPI) and the
      Thai Mental State Examination (TMSE). RESULTS: The subjects were female 62.9% and
      male 37.1%, the mean age was 76 +/- 6.7 years. The majority of them (62.9%) were
      in the mild stage (CDR = 1). The result showed that the prevalence of
      neuropsychiatric symptoms (> or = 1 symptom) reported was 100%. The most common
      symptoms were apathy (71%), aberrant motor behavior (61.3%), sleep problems
      (56.5%), eating problems (51.6%) and agitation/aggression (45.2%), whereas the
      least was euphoria (6.5%). The number of neuropsychiatric symptoms increased with
      severity of the disease. The result also showed that 61.3% of the participants
      presented with the chief complaint of neuropsychiatric symptoms, whereas memory
      complaints were only 38.7%. CONCLUSION: Neuropsychiatric symptoms are very common
      in Thai Alzheimer's disease patients. Therefore, management of Alzheimer's
      patients should include an assessment of neuropsychiatric symptoms and also
      concentrate on reducing these symptoms. The number of neuropsychiatric symptoms
      increases with disease progression. Moreover, neuropsychiatric symptoms were the
      most common presenting problem rather than memory problem in Thai patients with
      Alzheimer's disease.

PMID- 25065099
TI  - Multidisciplinary rounds have become a must, experts say.
AB  - Multidisciplinary rounds are a good way to improve throughput, reduce length of
      stay and readmissions, and improve patient satisfaction, experts say. They add:
      The meetings help the care team identify what is needed for discharge and get all
      of the disciplines on the same page. The structure and participants will vary by
      organization, but nursing, case management, finance, and pharmacy should be
      represented. The meetings should be at the same time and place every day and
      should last no more than 45 minutes.

PMID- 25065100
TI  - Keeping the team focused during rounds.

PMID- 25065101
TI  - Extended-stay rounds can help move patients along.
AB  - Weekly extended stay rounds help move along patients who have issues and barriers
      to a timely discharge, experts say. They recommend: Hold them at the same time
      and place each week and schedule an hour to an hour and a half for each meeting.
      Include the physician advisor for case management, a financial counselor, and
      representatives from case management, social work, therapy, nutrition, pharmacy,
      wound care, and other departments providing services to patients. Talk about the
      barriers and issues impeding discharge and brainstorm on solutions.

PMID- 25065102
TI  - Rounds help keep the treatment team on task.
AB  - Mercy Medical Center in Canton, OH, established daily multidisciplinary rounds at
      the same time the case management department was being redesigned. Committee
      developed expectations for the rounds, including a script and checklist.
      Management audits the meetings periodically to ensure that the format is being
      followed. The redesign extended hours of case management coverage and added
      weekend coverage.

PMID- 25065103
TI  - Time management for case managers--so much work, so little time.
AB  - The world of a case manager is a busy one, and you may not have all the resources
      you need each and every day. If you can maintain a routine it will make the
      workload more manageable for you and will allow room for those surprises that
      invariably happen. Whether you are a new or a seasoned case manager, organizing
      your workload can always help smooth out the rough edges in anyone's hectic day!

PMID- 25065104
TI  - Transition manager is liaison between teams.
AB  - At University of Utah Health Care, a transition case manager acts as a liaison
      between the outpatient care team at community clinics and the inpatient care
      team. The transition navigator works with case managers at the hospital and the
      clinics to make sure both have the information they need to coordinate care for
      the patient. The transition navigator visits patients in the hospital and works
      with the unit case manager to make sure the discharge plan will work. To further
      smooth transitions, the patients receive a one-page sheet that summarizes their
      discharge instructions, follow-up appointments, and medication regimen.

PMID- 25065105
TI  - Responding to ACA access problems.

PMID- 25065106
TI  - Lean in healthcare-- history and recent developments.

PMID- 25065107
TI  - Readiness factors for lean implementation in healthcare settings--a literature
      review.
AB  - PURPOSE: The purpose of this paper is to determine the readiness factors that are
      critical to the application and success of lean operating principles in
      healthcare organizations through a review of relevant literature.
      DESIGN/METHODOLOGY/APPROACH: A comprehensive review of literature focussing on
      lean and lean healthcare was conducted. FINDINGS: Leadership, organizational
      culture, communication, training, measurement, and reward systems are all
      commonly attributed readiness factors throughout general change management and
      lean literature. However, directly related to the successful implementation of
      lean in healthcare is that a setting is able to authorize a decentralized
      management style and undertake an end-to-end process view. These can be
      particularly difficult initiatives for complex organizations such as healthcare
      settings. RESEARCH LIMITATIONS/IMPLICATIONS: The readiness factors identified are
      based on a review of the published literature. The external validity of the
      findings could be enhanced if tested using an empirical study. PRACTICAL
      IMPLICATIONS: The readiness factors identified will enable healthcare
      practitioners to be better prepared as they begin their lean journeys.
      Sustainability of the lean initiative will be at stake if these readiness factors
      are not addressed. ORIGINALITY/VALUE: To the best of the knowledge, this is the
      first paper that provides a consolidated list of key lean readiness factors that
      can guide practice, as well as future theory and empirical research.

PMID- 25065108
TI  - Exploring the nature and impact of leadership on the local implementation of the
      Productive Ward Releasing Time to Care.
AB  - PURPOSE: The purpose of this paper is to explore the nature and impact of
      leadership in relation to the local implementation of quality improvement
      interventions in health care organisations. DESIGN/METHODOLOGY/APPROACH: Using
      empirical data from two studies of the implementation of The Productive Ward:
      Releasing Time to Care in English hospitals, the paper explores leadership in
      relation to local implementation. Data were attained from in-depth interviews
      with senior managers, middle managers and frontline staff (n = 79) in 13 NHS
      hospital case study sites. Framework Approach was used to explore staff views and
      to identify themes about leadership. FINDINGS: Four overall themes were
      identified: different leadership roles at multiple levels of the organisation,
      experiences of "good and bad" leadership styles, frontline staff having a sense
      of permission to lead change, leader's actions to spread learning and sustain
      improvements. ORIGINALITY/VALUE: This paper offers useful perspectives in
      understanding informal, emergent, developmental or shared "new" leadership
      because it emphasises that health care structures, systems and processes
      influence and shape interactions between the people who work within them. The
      framework of leadership processes developed could guide implementing
      organisations to achieve leadership at multiple levels, use appropriate
      leadership roles, styles and behaviours at different levels and stages of
      implementation, value and provide support for meaningful staff empowerment, and
      enable leader's boundary spanning activities to spread learning and sustain
      improvements.

PMID- 25065109
TI  - Lean in healthcare from employees' perspectives.
AB  - PURPOSE: The purpose of this paper is to contribute toward a deeper understanding
      of the new roles, responsibilities, and job characteristics of employees in Lean
      healthcare organizations. DESIGN/METHODOLOGY/APPROACH: The paper is based on
      three cases studies of healthcare organizations that are regarded as successful
      examples of Lean applications in the healthcare context. Data were collected by
      methods including interviews, observations, and document studies. FINDINGS: The
      implementation of Lean in healthcare settings has had a great influence on the
      roles, responsibilities, and job characteristics of the employees. The focus has
      shifted from healthcare professionals, where clinical autonomy and professional
      skills have been the guarding principles of patient care, to process improvement
      and teamwork. Different job characteristics may make it difficult to implement
      certain Lean practices in healthcare. Teamwork and decentralization of authority
      are examples of Lean practices that could be considered countercultural because
      of the strong professional culture and uneven power distribution, with doctors as
      the dominant decision makers. PRACTICAL IMPLICATIONS: Teamwork, value flow
      orientation, and company-wide involvement in CI were associated with positive
      effects on the organizations' working environment, staff development, and
      organizational performance. ORIGINALITY/VALUE: In order to succeed with Lean
      healthcare, it is important to understand and recognize the differences in job
      characteristics between Lean manufacturing and healthcare. This paper provides
      insights into how Lean implementation changes the roles, responsibilities, and
      job characteristics of healthcare staff and the challenges and implications that
      may follow from this.

PMID- 25065110
TI  - Does lean implementation interact with group functioning?
AB  - PURPOSE: As healthcare often is studied in relation to operational rather than
      socio-technical aspects of Lean such as teamwork, the purpose of this paper is to
      explore how a Swedish hospital Lean intervention was related to changes in
      teamwork over time. DESIGN/METHODOLOGY/APPROACH: Teamwork was measured with the
      Group Development Questionnaire (GDQ) employee survey during Lean implementation
      at three units, in 2010 (n = 133) and 2011 (n = 130). Qualitative data including
      interviews, observations and document analysis were used to characterize the Lean
      implementation and context. The expected teamwork change patterns were compared
      with GDQ data through linear regression analysis. FINDINGS: At Ward-I, Lean
      implementation was successful and teamwork improved. At Ward-II, Lean was
      partially implemented and teamwork improved slightly, while both Lean and
      teamwork deteriorated at the emergency department (ED). The regression analysis
      was significant at ED (p = 0.02) and the Ward-II (p = 0.04), but not at Ward-I (p
      = 0.11). RESEARCH LIMITATIONS/IMPLICATIONS: Expected changes in teamwork informed
      by theory and qualitative data may make it possible to detect the results of a
      complex change. PRACTICAL IMPLICATIONS: Overall, Lean may have some impact on
      teamwork, if properly implemented. However, this impact may be more prominent in
      relation to structural and productivity issues of teamwork than group members'
      relational issues. Practitioners should note that, with groups struggling with
      initial stages of group functioning, Lean may be very challenging.
      ORIGINALITY/VALUE: This study focussed specifically on implications of Lean for
      nurse teamwork in a hospital setting using both qualitative and quantitative
      data. Importantly, the group functioning at the time when Lean is initiated may
      affect the implementation of Lean.

PMID- 25065111
TI  - Implementing lean methods in the emergency department: the role of professions
      and professional status.
AB  - PURPOSE: The purpose of this paper is to examine the implementation of lean
      methods in an Emergency Department (ED) and the role of the professions in this
      process. DESIGN/METHODOLOGY/APPROACH: Qualitative, semi-structured interviews
      with ED staff in a UK NHS hospital. FINDINGS: Lean was met with more engagement
      and enthusiasm by the professionals than is usually reported in the literature.
      The main reasons for this were a combination of a national policy, the unique
      clinical environment and the status of the professional project for doctors in
      emergency medicine. RESEARCH LIMITATIONS/IMPLICATIONS: Single site, one-off
      study. PRACTICAL IMPLICATIONS: The status and development of professionals
      involved may play a big part in the acceptability of initiatives like lean
      methods in health care. The longer-term sustainability of the organisational
      changes introduced remains open to question. ORIGINALITY/VALUE: This paper
      analyses the success of lean methods in health care with reference to the
      professional status and stage of development of the professions involved, using
      the sociology of professions. This approach has not been used elsewhere.

PMID- 25065112
TI  - Applying lean flows in pathology laboratory remodelling.
AB  - PURPOSE: This purpose of this paper is to examine the application and outcomes of
      applying all of the seven lean flows to pathology laboratory remodelling as part
      of a lean rapid improvement event (RIE). DESIGN/METHODOLOGY/APPROACH:
      Longitudinal case study of a lean RIE linking emergency and pathology departments
      focusing on the systematic application of lean's seven flows to the physical
      environment. FINDINGS: Following the lean RIE, changes improving patient
      specimen, technician, supplies and information flows avoided 187 km and eight
      days of unnecessary walking each year. RESEARCH LIMITATIONS/IMPLICATIONS: The
      difficulty of making accurate comparisons between time periods in a health care
      setting is acknowledged. PRACTICAL IMPLICATIONS: This research provides evidence
      that applying lean design concepts in a laboratory can make substantial
      improvements, particularly if the expertise of the people working in the
      laboratory is trusted to determine the most appropriate changes. Significant
      amounts of time and motion were saved by just one, easily quantifiable change.
      SOCIAL IMPLICATIONS: The laboratory staff is processing increased numbers of time
      critical tests, yet report a calmer working environment, without any increase in
      the pace of work. Laboratory personnel also experienced satisfaction in
      exercising control over their work environment. ORIGINALITY/VALUE: To the best of
      the authors' knowledge this is the first comprehensive report applying lean flows
      to pathology laboratory remodelling and one of the few applications of Lean
      Systems Thinking between departments and between separate health services
      organisations.

PMID- 25065113
TI  - Squaring the circle of healthcare supplies.
AB  - PURPOSE: The purpose of this paper is to use a systems lens to assess the
      comparative performance of healthcare supply chains and provide guidance for
      their improvement. DESIGN/METHODOLOGY/APPROACH: A well-established and rigorous
      multi-method audit methodology, based on the uncertainty circle model, yields an
      objective assessment of value stream performance in eight Australasian public
      sector hospitals. Cause-effect analysis identifies the major barriers to
      achieving smooth, seamless flows. Potentially high-leverage remedial actions
      identified using systems thinking are examined with the aid of an exemplar case.
      FINDINGS: The majority of the healthcare value streams studied are
      underperforming compared with those in the European automotive industry. Every
      public hospital appears to be caught in the grip of vicious circles of system
      uncertainty, in large part being caused by problems of their own making. The
      single exception is making good progress towards seamless functional integration,
      which has been achieved by elevating supply chain management to a core
      competence; having a clearly articulated supply chain vision; adopting a systems
      approach; and, managing supplies with accurate information. RESEARCH
      LIMITATIONS/IMPLICATIONS: The small number of cases limits the generalisability
      of the findings at this time. PRACTICAL IMPLICATIONS: Hospital supply chain
      managers endeavouring to achieve smooth and seamless supply flows should attempt
      to elevate the status of supplies management within their organisation to that of
      a core competence, and should use accurate information to manage their value
      streams holistically as a set of interwoven processes. A four-level prism model
      is proposed as a useful framework for thus improving healthcare supply delivery
      systems. ORIGINALITY/VALUE: Material flow concepts originally developed to
      provide objective assessments of value stream performance in commercial settings
      are adapted for use in a healthcare setting. The ability to identify exemplar
      organisations via a context-free uncertainty measure, and to use systems thinking
      to identify high-leverage solutions, supports the transfer of appropriate best
      practices even between organisations in dissimilar business and economic
      settings.

PMID- 25065114
TI  - Complexity complicates lean: lessons from seven emergency services.
AB  - PURPOSE: The purpose of this paper is to explain how different emergency services
      adopt and adapt the same hospital-wide lean-inspired intervention and how this is
      reflected in hospital process performance data. DESIGN/METHODOLOGY/APPROACH: A
      multiple case study based on a realistic evaluation approach to identify
      mechanisms for how lean impacts process performance and services' capability to
      learn and continually improve. Four years of process performance data were
      collected from seven emergency services at a Swedish University Hospital: ear,
      nose and throat (ENT) (two), pediatrics (two), gynecology, internal medicine, and
      surgery. Performance patterns were linked with qualitative data collected through
      realist interviews. FINDINGS: The complexity of the care process influenced how
      improvement in access to care was achieved. For less complex care processes (ENT
      and gynecology), large and sustained improvement was mainly the result of a
      better match between capacity and demand. For medicine, surgery, and pediatrics,
      which exhibit greater care process complexity, sustainable, or continual
      improvement were constrained because the changes implemented were insufficient in
      addressing the higher degree of complexity. ORIGINALITY/VALUE: The variation in
      process performance and sustainability of results indicate that lean efforts
      should be carefully adapted to the complexity of the care process and to the
      educational commitment of healthcare organizations. Ultimately, the ability to
      adapt lean to a particular context of application depends on the development of
      routines that effectively support learning from daily practices.

PMID- 25065115
TI  - Multiple Wormian bones and their relation with definite pathological conditions
      in a case of an adult cranium.
AB  - Wormian bones, also known as intrasutural bones, are present as an anatomical
      variation in healthy individuals. However, a higher than the usual incidence can
      be an important feature of some congenital pathological conditions. In this study
      we describe a case of an adult cranium with multiple Wormian bones. The cranium
      was a single sample obtained from an archaeological excavation in Vinitsa,
      Northeastern Bulgaria, and probably dated in the Chalcolithic. The Chalcolithic
      is a period of human history connected with discovering and using of copper.
      Actually, it is a transitional phase between the Neolithic and the Bronze Age. In
      this case the Wormian bones are mostly large in size and arranged in a mosaic
      pattern in several cranial regions. The cranium also shows features such as
      dolichocrany, a moderate platybasia, a notch in the posterior margin of the
      foramen magnum, hypoplastic and asymmetrical frontal sinuses, underdeveloped
      mastoid air cells, hyperostosis cranii interna, moderate frontal bossing, a
      complete metopic suture, a delayed sutural closure, relatively small facial
      bones, an early loss of teeth, dental caries and hypoplastic enamel defects on
      two preserved molars. Differential diagnosis indicates that the combination of
      all these features shows a link with pathological conditions involving dysplasias
      with prominent membranous bone involvement and an increased bone density such as
      cleidocranial dysplasia and pyknodysostosis.

PMID- 25065116
TI  - Macroscopic anatomy of the vertebral endplate: quid significat?
AB  - Alterations of vertebral endplates have long been a subject of interest, but are
      of unclear clinical significance. The vertebral columns of a cohort-based sample
      of 850 individuals were therefore evaluated for vertebral endplate defects,
      noting adjacent vertebral size and shape variation, bone density and associated
      pathologies. Defects were found in the vertebral endplates of 458 individuals
      (Schmorl's nodes in 52.0% and linear defects in 10.6%). Vertebral centra
      osteophytes and diffuse idiopathic skeletal hyperostosis were more common;
      vertebral compression, less common in vertebrae with defects. Linear defects were
      more disseminated throughout the vertebral column, with individual defects more
      commonly affected either the interior half or the posterior quarter of the
      endplate or extended across all quarters form anterior to posterior. Individual
      Schmorl's nodes were predominantly limited to a single quarter. An inverse
      relationship was identified with tuberculosis. Spondyloarthropathy was more
      common in individuals with Schmorl's nodes, but not linear defects. Schmorl's
      nodes and linear endplate defects should be independently assessed, although they
      do share implications. Paradoxically, they are associated with phenomena which
      seem to mark increased ossification potential (osteophytes and diffuse idiopathic
      skeletal hyperostosis), but not with osteoporosis. Similarly, presence of
      Schmorl's nodes correlation with spondyloarthropathy, another disorder
      characterized by increased ossification potential. While correlation is not
      causality, inverse relationship to tuberculosis is intriguing, given the known
      relationship of spondyloarthropathy to tuberculosis and its antigens. Previously
      undescribed surface elevations were commonly associated with the presence of
      Schmorl's nodes and also correlated with disease, especially inflammatory
      arthritis, hypertrophic osteoarthropathy.

PMID- 25065117
TI  - The shape variability of human tibial epiphyses in an early medieval Great
      Moravian population (9th-10th century AD): a geometric morphometric assessment.
AB  - Limb bone morphology is influenced by external factors, including changes in
      subsistence and socioeconomic shifts. The aim of this study was to identify and
      describe any trends in morphological variation in human tibial epiphyses within
      an early medieval population of central Europe using surface scanning and
      geometric morphometric methods. The results are discussed in terms of three
      potential sources of variation in shape variability: sexual dimorphism, age at
      death and social status. These parameters were tested on a Great Moravian
      population sample (35 men and 30 women) from a Mikulcice settlement (9th-10th
      century AD). Proximal (13 landmarks) and distal (8 landmarks) tibial epiphyses
      were evaluated independently. The most significant differences in morphology of
      both articular ends were found between the groups separated by sex. Proximal
      tibial variability in the studied sample was characterized by a strong
      relationship between tibial size and shape of sexual dimorphic traits.
      Significant shape differences were also identified between adultus (20 - 40
      years) and maturus (40 - 60) age groups regarding the proximal epiphysis but
      neither of the epiphyses was affected by the presumed social status as derived
      from location within the context of the settlement.

PMID- 25065118
TI  - Craniofacial morphology in ancient and modern Greeks through 4,000 years.
AB  - BACKGROUND: Multiple 20th century studies have speculated on the anthropological
      similarities of the modern inhabitants of Greece with their ancient predecessors.
      The present investigation attempts to add to this knowledge by comparing the
      craniofacial configuration of 141 ancient (dating around 2,000-500 BC) and 240
      modern Greek skulls (the largest material among relevant national studies).
      METHOD: Skulls were grouped in age at death, sex, era and geographical
      categories; lateral cephalograms were taken and 53 variables were measured and
      correlated statistically. The craniofacial measurements and measurements of the
      basic quadrilateral and cranial polygon were compared in various groups using
      basic statistical methods, one-way ANOVA and assessment of the correlation
      matrices. OBSERVATIONS: Most of the measurements for both sexes combined followed
      an akin pattern in ancient and modern Greek skulls. Moreover, sketching and
      comparing the outline of the skull and upper face, we observed a clock-wise
      movement. The present study confirms that the morphological pattern of Greek
      skulls, as it changed during thousands of years, kept some characteristics
      unchanged, with others undergoing logical modifications. CONCLUSION: The analysis
      of our results allows us to believe that the influence upon the craniofacial
      complex of the various known factors, including genetic or environmental
      alterations, is apt to alter its form to adapt to new conditions. Even though
      4,000 years seems too narrow a span to provoke evolutionary insights using
      conventional geometric morphometrics, the full presentation of our results makes
      up a useful atlas of solid data. Interpreted with caution, the craniofacial
      morphology in modern and ancient Greeks indicates elements of ethnic group
      continuation within the unavoidable multicultural mixtures.

PMID- 25065119
TI  - The extent to which garments affect the assessment of body shapes of males from
      faceless CCTV images.
AB  - Closed circuit television (CCTV) systems are being widely used in crime
      surveillance. The images produced are of poor quality often face details are not
      visible, however expert witnesses in the field of biological anthropology use
      morphological descriptions of body shapes in an attempt to identify persons of
      interest. These methods can be applied to individual images when other cues such
      as gait, are not present. Criminals commonly disguise their faces, but body shape
      characteristics can be used to distinguish a person of interest from others.
      Garments may distort the body shape appearance, thus this study was undertaken to
      investigate the effects of garments on the description of body shape from CCTV
      images. Twelve adult males representing a wide body shape range of Sheldonian
      somatotypes were photographed in identical garments comprising of tight fitting
      black shirt, horizontally striped shirt, padded leather jacket and in naked
      torso. These photographs were assessed by 51 males and females aged 18-50 years,
      with varying levels of education, and different experience in use of CCTV images
      for identification of people, to identify the 12 participants. The effect of
      assessors was not significant. They correctly distinguished 88.6% of individuals
      wearing the same wear, but could not match the same individuals wearing different
      wear above the random expectations. However, they matched somatotypes above
      random expectation. Type of clothing produced little bias in somatotype matching;
      ectomorphic component of individuals wearing black shirts and padded jackets was
      overestimated and underestimated, respectively. In conclusion, type of the wear
      had little effect in the description of individuals from CCTV images using the
      body shapes.

PMID- 25065120
TI  - Y-SNP analysis versus Y-haplogroup predictor in the Slovak population.
AB  - Human Y-chromosome haplogroups are important markers used mainly in population
      genetic studies. The haplogroups are defined by several SNPs according to the
      phylogeny and international nomenclature. The alternative method to estimate the
      Y-chromosome haplogroups is to predict Y-chromosome haplotypes from a set of Y
      STR markers using software for Y-haplogroup prediction. The purpose of this study
      was to compare the accuracy of three types of Y-haplogroup prediction software
      and to determine the structure of Slovak population revealed by the Y-chromosome
      haplogroups. We used a sample of 166 Slovak males in which 12 Y-STR markers were
      genotyped in our previous study. These results were analyzed by three different
      software products that predict Y-haplogroups. To estimate the accuracy of these
      prediction software, Y-haplogroups were determined in the same sample by
      genotyping Y-chromosome SNPs. Haplogroups were correctly predicted in 98.80%
      (Whit Athey's Haplogroup Predictor), 97.59% (Jim Cullen's Haplogroup Predictor)
      and 98.19% (YPredictor by Vadim Urasin 1.5.0) of individuals. The occurrence of
      errors in Y-chromosome haplogroup prediction suggests that the validation using
      SNP analysis is appropriate when high accuracy is required. The results of SNP
      based haplotype determination indicate that 39.15% of the Slovak population
      belongs to R1a-M198 lineage, which is one of the main European lineages.

PMID- 25065121
TI  - Secular changes in body size and body composition in schoolchildren from La Plata
      City (Argentina).
AB  - AIM: To analyze the secular changes in body size and composition of two cohorts
      of children from La Plata City, Argentina, with a 35-year follow-up. subjects and
      methods: Cohort 1 (C1) was measured in 1969-1970 and included 1772 children (889
      boys, 883 girls), and Cohort 2 (C2), measured in 2004-2005, included 1059
      children (542 boys, 517 girls). Both cohorts were obtained from matching
      geographical areas and comprised children from 4 to 12 years. Body weight (W);
      Height (H); Upper arm circumference (UAC); Tricipital (TS) and Subscapular
      skinfolds (SS) were measured, and Body Mass Index (BMI) and muscle (UMA) and fat
      (AFA) brachial areas were calculated. Prevalence of overweight and obesity was
      estimated by IOTF. To compare C1-C2 we used a generalized linear model with log
      transformed variables, and chi square test. RESULTS: There were significant and
      positive differences between C2-C1 in W, UAC, SS, TS, and AFA. In contrast, H was
      not significantly different and UMA was significantly different but with negative
      values. The prevalence of overweight and obesity was 14.5% and 3.8% in C1, and
      17.0% and 6.8% in C2. Differences between cohorts were significant for obesity.
      CONCLUSION: The shifts observed for soft tissues--positive trend for fat and
      negative for muscle area--occurring without changes in height lead us to suppose
      that in these three decades, La Plata's population has experienced deterioration
      in living conditions and important changes in their lifestyle, such as an
      increased consumption of energy-dense foods and sedentary habits.

PMID- 25065122
TI  - Effects of parental reproductive behavior on offspring sex ratio in a pre
      industrial western Mediterranean population (La Alpujarra, 1900-1950, SE Spain).
AB  - The reproductive behavior of parents of La Alpujarra (Spain) favorable to male
      offspring during the first half of the 20th century has been studied is this
      paper. The family size increased as daughters accumulated because mothers had
      more pregnancies in order to have higher male offspring, and the reproductive
      rhythm increased (birth interval decreased) when the first deliveries were only
      daughters. Although male mortality was higher than female in children older than
      one year, this reproductive behavior did not determine sex reversal of mortality
      in babies of between one month and one year, contrary to other developing
      populations.

PMID- 25065123
TI  - First report on trichomonads from true bugs.
AB  - Although the hindgut of some insects represents a rich source of intestinal
      trichomonads, their diversity is only poorly understood. The aim of the present
      study was to investigate the presence and abundance of intestinal trichomonads in
      true bugs (Heteroptera). We microscopically examined intestinal contents of more
      than 780 specimens belonging to 28 families of true bugs from localities in
      China, Ghana and Papua New Guinea for the presence of intestinal endosymbionts.
      More than 120 samples were examined also by means of PCR using trichomonad
      specific primers. We determined sequences of SSU rDNA and ITS region of two
      isolates of the genus Simplicimonas Cepicka, Hampl et Kulda, 2010 and one isolate
      of Monocercomonas colubrorum (Hammerschmidt, 1844). Although our results showed
      that trichomonads are very rare inhabitants of the intestine of true bugs, two of
      three isolated flagellates belong to species specific for reptiles. The
      possibility of transmission of trichomonads between reptiles and true bugs is
      discussed.

PMID- 25065124
TI  - Four new species of coccidia (Apicomplexa: Eimeriidae) from Owen Stanley Skinks,
      Papuascincus stanleyanus (Sauria: Scincidae), from Papua New Guinea.
AB  - Between September and November 1991, 12 Owen Stanley skinks, Papuascincus
      stanleyanus (Booulenger) were collected from various localities on Papua New
      Guinea and examined for coccidians. Six (50%) were found to harbour four
      eimerians that we describe here as new. Oocysts of Eimeria burseyi sp. n. were
      elongate to ellipsoidal with a bilayered wall and measured (length x width, L x
      W) 36.0 x 24.0 microm, with a L/W ratio of 1.5. Both micropyle and oocyst
      residuum were absent, but a polar granule was present. Oocysts of Eimeria
      goldbergi sp. n. were ellipsoidal, with a bilayered wall, and measured 21.4 x
      16.1 microm; L/W ratio was 1.3. Both micropyle and oocyst residuum were absent,
      but a single or fragmented polar granule was present. Oocysts of Eimeria
      boulengeri sp. n. were spheroidal to slightly subspheroidal, with a thin, single
      layered wall that readily collapses, and measured 16.0 microm, L/W ratio was 1.0.
      Both micropyle and oocyst residuum were absent, but usually one (sometimes two)
      polar granule(s) were present. Oocysts of Eimeria niuginiensis sp. n. were oblong
      to tapered with a bilayered wall, and measured 20.0 x 13.1 microm; L/W ratio was
      1.5. A micropyle, oocyst residuum and polar granule were absent. To our
      knowledge, these represent the only coccidians ever described from P.
      stanleyanus.

PMID- 25065125
TI  - Choleoeimeria salaselensis sp. n. (Apicomplexa: Eimeriidae) from the gall bladder
      of the horned viper Cerastes gasperettii (Serpentes: Viperidae) in Saudi Arabia.
AB  - Oocyst morphology and endogenous developmental stages are described for
      Choleoeimeria salaselensis sp. n. from the gall bladder of 10 horned vipers,
      Cerastes gasperettii Leviton and Anderson, in Saudi Arabia. Sporulated oocysts
      are ellipsoidal, 23 x 15 (22-25 x 14-17) microm, length/width ratio (L/W) 1.5
      (1.4-1.6), each with 4 sporocysts (Eimeria-like), but lack a micropyle, polar
      granules and oocysts residuum. Sporocysts are ellipsoidal, 8 x 5 (7-9 x 5-)
      microm, L/W 1.5 (1.4-1.6), and Stieda, substieda and parasubstieda bodies are all
      absent, but a longitudinal suture, which divided the sporocysts into 2 plates, is
      present. Endogenous development is confined to epithelial cells in the bile duct
      and gall bladder; mature meronts were 11 x 7 microm, each with 10-16 merozoites,
      microgamonts were -12 microm wide, and macrogamonts were -16 microm wide with a
      prominent nucleus and wall-forming bodies. Given these two diagnostic features,
      sporocysts with a suture and composed of two plates and endogenous development
      limited to the biliary epithelium, we believe this coccidium is best classified
      as a member of Choleoeimeria Paperna et Landsberg, 1989. There are 5 known
      Eimeria species from vipers that have sporocysts somewhat similar in size to
      those of our new form, but all of them have much larger oocysts and larger
      sporocysts, some of which differ significantly in shape; there are not yet any
      Choleoeimeria species known from the Viperidae.

PMID- 25065126
TI  - Merizocotyle euzeti sp. n. (Monogenea: Monocotylidae) from the nasal tissue of
      three deep sea skates (Rajidae) in the southwestern Atlantic Ocean.
AB  - A new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae) is
      described from the nasal tissues of three deep sea rajid skates: the southern
      thorny skate, Amblyraja doellojuradoi (Pozzi), broadnose skate, Bathyraja
      brachyurops (Fowler), and yellownose skate, Zearaja chilensis (Guichenot),
      collected off Buenos Aires Province, Argentina, southwest Atlantic Ocean. Two
      additional species of sympatric rajid, the white-dotted skate, Bathyraja
      albomaculata (Norman), and the Patagonian skate, Bathyraja macloviana (Norman),
      were also examined but no merizocotylines were found. The taxonomy of the
      Merizocotylinae is not widely accepted and, as a result, the status of
      Thaumatocotyle and Mycteronastes, and their proposed synonymy with Merizocotyle
      are currently under discussion. The new species differs from its congeners by
      having a unique haptoral structure, 6 peripheral loculi that are asymmetrically
      arranged (one much smaller, indistinctly located in the left or right side of the
      haptor). The presence of the new species in three sympatric species of Rajidae
      belonging to distinct genera and subfamilies, as well as its absence in sympatric
      congenerics indicates the lack of phylogenetic host specificity. Host ecology and
      geographical distribution appear to be more important than host phylogeny in
      determining the distribution of this parasite across potential hosts in the
      region. This constitutes the first record of Merizocotyle in the southwestern
      Atlantic Ocean.

PMID- 25065127
TI  - Neotropical Monogenoidea. 58. Three new species of Gyrodactylus (Gyrodactylidae)
      from Scleromystax spp. (Callichthyidae) and the proposal of COII gene as an
      additional fragment for barcoding gyrodactylids.
AB  - Based on molecular markers (COII and ITS1-ITS2) and morphological data, we
      describe three new Neotropical species of Gyrodactylus von Nordmann, 1832 from
      Scleromystax barbatus (Quoy et Gaimard) and Scleromystax macropterus (Regan) from
      southern Brazil. The three new species can be distinguished from each other by
      sequences of both molecular markers and morphology of hooks and anchors.
      Gyrodactylus bueni sp. n. is characterised by having hook with shaft curved, heel
      straight, shelf straight, toe pointed, anchor with superficial root slender,
      elongate and male copulatory organ armed with two rows of spinelets. Gyrodactylus
      major sp. n. presents hook with shaft, point curved, proximal shaft straight,
      heel convex, shelf convex, toe concave, anchor with superficial root robust and
      male copulatory organ armed with two rows of spinelets. Gyrodactylus
      scleromystaci sp. n. presents hook with shaft, point recurved, heel convex, shelf
      convex, toe pointed, anchor with superficial root curved and male copulatory
      organ armed with two rows of spinelets. These species appear to be closely
      related to other species of Gyrodactylus known from other species of
      Callichthyidae. These new species, however, differ by the comparative morphology
      of the haptoral hard structures and molecular data. Comparative analysis of
      sequences from these species of Gyrodactylus suggests that the COII gene may
      represent an important marker for the taxonomy of species of Gyrodactylidae and,
      perhaps, for species of other lineages of Monogenoidea.

PMID- 25065128
TI  - New genus of opecoelid trematode from Pristipomoides aquilonaris (Perciformes:
      Lutjanidae) and its phylogenetic affinity within the family Opecoelidae.
AB  - Bentholebouria colubrosa gen. n. et sp. n. (Digenea: Opecoelidae) is described in
      the wenchman, Pristipomoides aquilonaris (Goode et Bean), from the eastern Gulf
      of Mexico, and new combinations are proposed: Bentholebouria blatta (Bray et
      Justine, 2009) comb. n., Bentholebouria longisaccula (Yamaguti, 1970) comb. n.,
      Bentholebouria rooseveltiae (Yamaguti, 1970) comb. n., and Bentholebouria ulaula
      (Yamaguti, 1970) comb. n. The new genus is morphologically similar to Neolebouria
      Gibson, 1976, but with a longer cirrus sac, entire testes, a rounded posterior
      margin with a cleft, and an apparent restriction to the deepwater snappers.
      Morphologically, the new species is closest to B. blatta from Pristipomoides
      argyrogrammicus (Valenciennes) off New Caledonia but can be differentiated by the
      nature of the internal seminal vesicle (2-6 turns or loops rather than
      constrictions), a longer internal seminal vesicle (occupying about 65% rather
      than 50% of the cirrus sac), a cirrus sac that extends further into the hindbody
      (averaging 136% rather than 103% of the distance from the posterior margin of the
      ventral sucker to the ovary), and a narrower body (27% rather than 35% mean width
      as % of body length). A Bayesian inference analysis of partial sequence of the
      28S rDNA from Neolebouria lanceolata (Price, 1934), Cainocreadium lintoni
      (Siddiqi et Cable, 1960), Hamacreadium mutabile Linton, 1910, Opecoeloides
      fimbriatus (Linton, 1910), Podocotyloides brevis Andres et Overstreet, 2013, the
      new species, and previously published comparable sequences from 10 opecoelid
      species revealed two clades. One clade includes deep-sea (> or = 200 m) and
      freshwater fish opecoelids + Opecoeloides Bremser in Rudolphi, 1819, and a second
      clade included those opecoelids from shallow-water marine, perciform fishes.

PMID- 25065129
TI  - Seussapex, a new genus of lecanicephalidean tapeworm (Platyhelminthes: Cestoda)
      from the stingray genus Himantura (Myliobatiformes: Dasyatidae) in the Indo-West
      Pacific with investigation of mode of attachment.
AB  - A new lecanicephalidean genus, Seussapex gen. n., is erected for specimens
      collected from stingrays from the Indo-West Pacific resembling the little known
      species Tenia [sic] narinari MacCallum, 1917 from the spotted eagle ray,
      Aetobatus narinari (Euphrasen). Members of this new genus are unique in their
      possession of a multi-tiered apical structure comprising a bipartite apical
      modification of the scolex proper, and an externally bipartite apical organ with
      anterior and posterior glandular compartments internally. The appearance of the
      scolex varies dramatically depending on state of protrusion and/or evagination of
      these different parts which appear to be able to function independently.
      Seussapex karybares sp. n. parasitizing Himantura uarnak 2 (sensu Naylor et al.,
      2012) in northern Australia is described as the type species and Tenia [sic]
      narinari is transferred to the new genus. The two species differ in scolex length
      and width of the posterior dome-shaped portion of the apical organ. Histological
      sections of scoleces stained using the periodic acid-Schiff(PAS) reaction showed
      the surface of the anterior part of the apical organ and the anterior glandular
      compartment to stain PAS positive, suggesting a chemical mode of attachment to
      the host's intestinal mucosal surface. Extensive collecting efforts of stingrays
      in the Indo-West Pacific shows Seussapex gen. n. to be restricted to species of
      Himantura Miller et Henle and suggests additional diversity in this group of
      hosts. In addition, the host identity of Seussapex narinari (MacCallum, 1917)
      comb. n. is called into question.

PMID- 25065130
TI  - The relationships of marsupial-dwelling Viannaiidae and description of
      Travassostrongylus scheibelorum sp. n. (Trichostrongylina: Heligmosomoidea) from
      mouse opossums (Didelphidae) from French Guiana.
AB  - The trichostrongylid nematode Travassostrongylus scheibelorum sp. n. from the
      Linnaeus' mouse opossum, Marmosa murina (Linnaeus) (type host), and the woolly
      mouse opossum, Marmosa demerarae (Thomas), from French Guiana is described. The
      nematodes have a synlophe with ridges frontally oriented from right to left, six
      dorsal and six ventral, at midbody; seven dorsal and seven ventral posterior to
      the vulva, and two cuticular thickenings within the lateral spaces; a long dorsal
      ray and a pointed cuticular flap covering the vulva. This is the 12th species of
      Travassostrongylus Orloff, 1933, which includes species featuring ridges around
      the synlophe and a didelphic condition. These traits contrast with those in other
      genera in the Viannaiidae Neveu-Lemaire, 1934, which feature ventral ridges on
      the synlophe of adults and a monodelphic condition. Members of the family are
      chiefly Neotropical and are diagnosed based on the presence of a bursa of the
      type 2-2-1, 2-1-2 or irregular, and cuticle without ridges on the dorsal side (at
      least during one stage of their development). Herein, we present a reconstruction
      of the ancestral states of the didelphic/monodelphic condition and the cuticular
      ridges that form the synlophe in opossum-dwelling trichostrongyles, namely
      Travassostrongylus and Viannaia Travassos, 1914. Our investigations suggest they
      are not reciprocal sister taxa and that the change from didelphy to monodelphy
      and the loss of dorsal ridges, occurred in the common ancestor of species of
      Viannaia. These results suggest a synlophe with three ventral ridges is not
      plesiomorphic in the opossum dwelling trichostrongylids.

PMID- 25065131
TI  - Uncinaria sanguinis sp. n. (Nematoda: Ancylostomatidae) from the endangered
      Australian sea lion, Neophoca cinerea (Carnivora: Otariidae).
AB  - This study investigates the identity of hookworms parasitising the Australian sea
      lion, Neophoca cinerea (Peron), from three colonies in South Australia,
      Australia. The Australian sea lion is at risk of extinction because its
      population is small and genetically fragmented. Using morphological and molecular
      techniques, we describe a single novel species, Uncinaria sanguinis sp. n.
      (Nematoda: Ancylostomatidae). The new species is most similar to hookworms also
      parasitic in otariid hosts, Uncinaria lucasi Stiles, 1901 and Uncinaria hamiltoni
      Baylis, 1933. Comparative morphometrics offered limited utility for
      distinguishing between species within this genus whilst morphological features
      and differences in nuclear ribosomal DNA sequences delineated U. sanguinis sp. n.
      from named congeners. Male specimens of U. sanguinis sp. n. differ from U. lucasi
      and U. hamiltoni by relatively shorter anterolateral and externodorsal rays,
      respectively, and from other congeners by the relative lengths and angulations of
      bursal rays, and in the shape of the spicules. Female specimens of U. sanguinis
      sp. n. are differentiated from Uncinaria spp. parasitic in terrestrial mammals by
      differences in vulval anatomy and the larger size of their eggs, although are
      morphologically indistinguishable from U. lucasi and U. hamiltoni. Molecular
      techniques clearly delimited U. sanguinis sp. n. as a distinct novel species.
      Obtaining baseline data on the parasites of wildlife hosts is important for the
      investigation of disease and the effective implementation and monitoring of
      conservation management.

PMID- 25065132
TI  - The systematic status of Piscinema barakensis [sic] Gambhir et Ng, 2014 and
      Rhabdochona carpiae Nimbalkar, Deolalikar et Kamtikar, 2013, two nematodes
      recently described from freshwater fishes in India.
AB  - Based on the original description, the nematode genus Piscinema Gambhir et Ng,
      2014 and its type species, P. barakensis [sic] Gambhir et Ng, 2014 (probably a
      misidentified physalopterid larvae), are removed from the Philometridae, where
      they were allocated; they are considered a genus inquirendum and incertae sedis
      and a species inquirenda, respectively. The poorly described nematode Rhabdochona
      carpiae Nimbalkar, Deolalikar et Kamtikar, 2013 (Rhabdochonidae) appears largely
      fabricated and is regarded a species dubia.

PMID- 25065133
TI  - Huffmanela hamo sp. n. (Nematoda: Trichosomoididae: Huffmanelinae) from the
      dagger-tooth pike conger Muraenesox cinereus off Japan.
AB  - Huffmanela hamo sp. n. is described from eggs only, which were found in black
      spots in the somatic musculature of a dagger-tooth pike conger, Muraenesox
      cinereus (Forsskal), caught off Japan. The eggs are 66-77 microm (mean 72 microm)
      in length and 33-38 microm (mean 35 microm) in width. The surface of the eggs is
      smooth and bears neither envelope nor filaments. The species is distinguished
      from other members of the genus by the dimensions of its eggs and the
      characteristics of their surface. This is the first species of Huffmanela
      Moravec, 1987 to be described from an anguilliform fish, and the twentieth
      nominal species in the genus. Similar black spots with eggs were reported four
      times in ten years from this fish caught off Japan; although eggs could not be
      examined, it is likely that the same species was involved in all cases.

PMID- 25065134
TI  - DNA barcodes reveal female dimorphism in syringophilid mites (Actinotrichida:
      Prostigmata: Cheyletoidea): Stibarokris phoeniconaias and Ciconichenophilus
      phoeniconaias are conspecific.
AB  - Here we present the first evidence of female dimorphism in ectoparasitic quill
      mites of the family Syringophilidae (Actinotrichida: Prostigmata: Cheyletoidea).
      Stibarokris phoeniconaias Skoracki et OConnor, 2010 and Ciconichenophilus
      phoeniconaias Skoracki et OConnor, 2010 so far have been treated as two distinct
      species cohabiting inside the quills of feathers of the lesser flamingo
      Phoeniconaias minor (Geoffroy Saint-Hilaire) and the American flamingo
      Phoenicopterus ruber Linnaeus. Although females of these species differ
      morphologically by the extent of body sclerotisation, presence/absence of lateral
      hypostomal teeth, and shape of dorsal setae, their important common features are
      the lack of leg setae vs II, and both stylophore and peritremes shape. Here, we
      apply the DNA barcode markers to test whether the differences between S.
      phoeniconaias and C. phoeniconaias have a genetic basis, indicating that they
      really are distinct taxa, or whether they just represent two morphs of a single
      species. All analysed sequences (616 bp for COI and 1159 bp for 28S rDNA)
      obtained for specimens representing females of both studied taxa as well as male,
      tritonymph, protonymph and larva of S. phoeniconaias were identical, which
      indicates that S. phoeniconaias and C. phoeniconaias are conspecific. The formal
      taxonomic consequence of our results is denial of the genus status of
      Ciconichenophilus Skoracki et OConnor, 2010 and species status of C.
      phoeniconaias, and recommendation that they should be treated as junior synonyms
      of Stibarokris Kethley, 1970 and S. phoeniconaias, respectively.

PMID- 25065135
TI  - Life cycle of the fish parasite Gnathia maxillaris (Crustacea: Isopoda:
      Gnathiidae).
AB  - The taxonomic classification of some parasitic isopods of the family Gnathiidae
      has been revised in the last years. However, their biological cycles have been
      described only partially or incompletely. Gnathia maxillaris (Montagu, 1804) is
      one of the most studied species, but certain aspects of its life cycle are still
      poorly known. A detailed study on the life cycle of G. maxillaris was carried out
      over several years by sampling larvae from an infestation of large volume aquaria
      at the Aquarium of Barcelona. At the same time, a system of in vitro cultivation
      of G. maxillaris was developed, which provided new data to complete the
      description of its life cycle. Periods of incubation, fertilization, planktonic
      stages, the attachment site on the fish host and biometric characteristics of
      larval forms were detailed. The new information may help better control health
      state of marine fish in aquaculture.

PMID- 25065136
TI  - [Cell therapy using stem cells: trophic factor, differentiation, and cell
      transplantation].
AB  - Our research of stem cell transplantation using mouse embryonic stem (ES) cells
      and induced pluripotent (iPS) cells was carried out from the aspect of trophic
      factor, cell differentiation, and better survival of grafted cells. Pleiotrophin,
      an enhanced trophic factor in the dopamine (DA)-depleted striatum, increased the
      number of DAergic neurons from ES-derived neural stem cells (ES-NSCs), increased
      cell survival of cultured DAergic neurons, and affected cell survival of grafted
      DAergic cells in Parkinson model rats. It was shown that DAergic differentiation
      from ES-NSCs was mediated by hypoxia inducible factor 1-alpha. Our challenges of
      the transplantation of ES-NSCs and iPS-derived oligodendrocyte progenitor cells
      (iPS-OPCs) into periventricular leukomalasia (PVL) model rats are also presented.
      It was found that grafted ES-NSCs survived better in the corpus callosum without
      immunosuppressant and most of them differentiated into neurons near the grafted
      site. It was also revealed that only a few of the grafted iPS-OPCs induced by a
      stepwise culture method with no use of serum could survive in PVL model rats,
      indicating that trophic factor (s) and improvement of graft techniques will be
      needed for better survival of grafted iPS-OPCs.

PMID- 25065137
TI  - [Man meets snake].
AB  - The author reviews recent findings of a series of experimental studies on snake
      detection in visual search which he himself has undertaken. It reveals that this
      method is quite useful as an experimental paradigm to investigate anxiety levels
      of humans whether they are adults or children.

PMID- 25065138
TI  - [The molecular basis for the protection and axon regeneration of motor neurons
      after nerve injury].
AB  - This review addresses the morphological changes seen in motor neurons and the
      surrounding non-neuronal cells in the process of regeneration after nerve injury.
      In addition, the molecular basis for the morphological changes and the gene
      expression regulation are also addressed. In the CNS, morphological changes of
      astrocyte and microglia are seen in response to nerve injury, which could be
      important for neuron survival. In the periphery Schwann cells, macrophages and
      endoneurial fibroblasts play crucial roles in proper nerve regeneration. For
      those cellular functions and behaviors, a significant number of mediators among
      those cells is expressed. In addition to thase intercellular signalings, the
      intracellular signaling in injured motor neurons is also crucial. In the injured
      motor neurons, their fate appears to be determined by a balance of the protection
      and death signals. To properly control expression of those signals, some
      regeneration-specific transcription factor complexes as well as the epigenetic
      regulators are emerging.

PMID- 25065139
TI  - [Vaccines as an approach to the immunocorrection in herpetic infections].
AB  - Development of vaccines for immunologic correction in herpetic infections is an
      important problem that raises a growing concern worldwide. The data on the
      experimental studies of the efficacy of an inactivated whole-virion vaccine
      against herpes simplex viruses types 1 and 2 (HSV-1 and -2) using an animal model
      are discussed. The results of the multiyear application of the vaccine to
      ophthalmology and dermatology practice are also presented. The results
      unambiguously show a high efficacy of the vaccine in the prevention of
      recurrences of the infections based on activation of specific T-cell response. A
      live vaccine against the varicella zoster virus (VZV) was developed for control
      of the infection in children. For the cytomegalovirus (CMV) infection in adults,
      inactivated whole-virion vaccines are at the stage of development. An important
      part of the study addresses a combined application of the inactivated vaccines
      with immunomodulators.

PMID- 25065140
TI  - [Genetic characterization of the Zaliv Terpeniya virus (ZTV, Bunyaviridae,
      Phlebovirus, Uukuniemi serogroup) strains isolated from the ticks Ixodes
      (Ceratixodes) uriae White, 1852, obligate parasites of the Alcidae birds, in high
      latitudes of Northern Eurasia and the mosquitoes Culex modestus Ficalbi, 1889, in
      subtropics Transcaucasus].
AB  - Complete genome sequences were obtained for the LEIV-13841Ka (ID GenBank KF767463
      65) and LEIV-279Az (ID GenBank KF767460-62) virus strains, which were classified
      as different strains of the Zaliv Terpeniya virus (ZTV). LEIV-13841Ka was
      isolated from the ticks Ixodes (Ceratixodes) uriae White, 1852 collected on Ariy
      Kamen (Commander Islands) in 1986. LEIV-279Az was isolated from the mosquitoes
      Culex modestus Ficalbi, 1889, collected in heron colony (Ardea Linnaeus, 1758) in
      Azerbaijan (1969) and was initially identified as Uukuniemi virus (UUKV).
      According to the results obtained LEIV-279Az is ZTV strain as well. LEIV-13841Ka
      and LEIV-279Az RdRp sequences have high level of homology (99%) with previously
      sequenced ZTV/LEIV-271Ka. The L-segment nucleotide sequences are homological with
      ZTV/LEIV-271Ka on the level of 94% and 98% for LEIV-13841Ka and LEIV-279Az,
      respectively; M-segment--89% and 88%, respectively. Such homologies for the amino
      acid sequences of Gn/Gc polyprotein are 98.3% and 97.7%. NP proteins of ZTV/LEIV
      13841Ka and LEIV-279Az have 88.7% and 84.6% homologies with ZTV/LEIV-271Ka both
      for amino acid and nucleotide sequences, respectively. Thus, for the very first
      time we demonstrated ZTV strain isolated from mosquitoes in subtropical
      Transcaucasia zone. Obtained results permit to expand suggested areal of ZTV and
      to fill up data upon the ecology of the Uukuniemi virus group.

PMID- 25065141
TI  - [Genetic characterization of viruses from the antigenic complex Tyuleniy
      (Flaviviridae, Flavivirus): Tyuleniy virus (TYUV) (ID GenBank KF815939) isolated
      from ectoparasites of colonial seabirds--Ixodes (Ceratixodes) uriae White, 1852,
      ticks collected in the high latitudes of Northern Eurasia--and Kama virus (KAMV)
      isolated from the Ixodes lividus Roch, 1844, collected in the digging colonies of
      the middle part of Russian plane].
AB  - Genetic research into the Tyuleniy virus (TYUV) (ID GenBank KF815939) isolated in
      high latitudes from the Ixodes uriae White, 1852, ticks collected in the nesting
      colonies of the Alcidae (Leach, 1820) birds and Kama virus (KAMV) (ID GenBank
      KF815940) isolated from the I. lividus ticks collected in the nesting bird
      colonies in the middle part of the Russian Plane was carried out. Full-genome
      comparative analysis revealed 70% homology between KAMV and TYUV on the
      nucleotide level and 74% on the amino acid level. Thus, KAMV is a new member of
      the TYUV complex belonging to the seabird tick-borne virus group (STBVG) of
      Flavivirus (Flaviviridae). KAMV is a separate virus and forms separate
      phylogenetic line together with the TYUV, Meaban virus (MEAV), and Saumarez Reef
      virus (SREV).

PMID- 25065143
TI  - [Taxonomy of the Sokuluk virus (SOKV) (Flaviviridae, Flavivirus, Entebbe bat
      virus group) isolated from bats (Vespertilio pipistrellus Schreber, 1774), ticks
      (Argasidae Koch, 1844), and birds in Kyrgyzstan].
AB  - Complete genome sequencing of the Sokuluk virus (SOKV) isolated in Kyrgyzstan
      from bats Vespertilio pipistrellus and their obligatory parasites--Argasidae
      Koch, 1844, ticks was carried out. SOKV was classified as attributed to the
      Flaviviridae family, Flavivirus genus. The maximum homology (71% for nucleotide
      and 79% for amino acid sequences) was detected with respect to the Entebbe bat
      virus (ENTV). ENTV and SOKV form a group joining to the yellow fever virus (YFV)
      within the limits of the mosquito flavivirus branch. Close relation of SOKV with
      bat covers and human housings permits to assume SOKV potentially patogenic to
      human health.

PMID- 25065142
TI  - [Genetic characterization of the Caspiy virus (CASV) (Bunyaviridae, Nairovirus)
      isolated from the Laridae (Vigors, 1825) and Sternidae (Bonaparte, 1838) birds
      and the Argasidae (Koch, 1844) ticks Ornithodoros capensis Neumann, 1901, in
      Western and Eastern coasts of the Caspian Sea].
AB  - Full-genome sequencing of the Caspiy virus (CASV - Caspiy virus) (ID GenBank
      KF801658) revealed its attribution to the Nairovirus genus of the Bunyaviridae
      family as a separate species. CASV forms separate line, which is the most close
      to the Hughes virus (HUGV) and Sakhalin virus (SAKV) groups containing viruses
      linked with seabirds and ticks parasitizing on them and distributed over the
      shelf and island ecosystems in the Northern Eurasia, as well as the North and
      South America.

PMID- 25065144
TI  - [Activity of the inositol-containing phospholipid dimer analogues against human
      immunodeficiency virus].
AB  - For the purpose of finding effective inhibitors of virus adsorption the series of
      inositol-containing phospholipid dimer analogues were previously synthesized. In
      the present work, the antiretroviral activity of these compounds against HIV-1
      was demonstrated on the model of cells infected with the virus. The highest
      effect was found in the case of dimer poliol 5, EC50 (50%-effective
      concentration) was 3.9 microg/ml. The development of new polyanionic compounds,
      which can interfere with early steps of the virus life cycle, is a promising
      addition to the antiretroviral therapy based on the virus enzyme inhibitors.

PMID- 25065145
TI  - [Research of suppression of the herpes simplex virus reproduction with drug
      resistance using a combination 15-Lys-bis-Nt with some antiherpetic drugs].
AB  - The antiviral effect of combinations of netropsin derivative 15-Lys-bis-Nt with
      the known antiherpetic compounds, whose activity does not depend on viral TK and
      which are able to inhibit replication of HSV in most cases, including strains
      resistant to acyclovir and pencyclovir, was studied. The combinations evoking
      additive, synergistic and significant synergistic effects of interaction of
      tested compounds were observed. The results obtained in this work indicated the
      possibility of significant reduction of concentrations of high toxic compounds in
      case of the combined use.

PMID- 25065146
TI  - [Intrafollicular infection of mammals and human oocytes by the herpes simplex
      virus].
AB  - The goal of this work was to study the capacity of the herpes simplex virus (HSV)
      of infecting ovary with disease in case of the intravaginal experimental animals.
      The results of the study demonstrated that the ascending HSV infection in mice
      lead to modification of all the cells of the ovary, including follicular cells
      synthesizing estrogen and progesterone. The two hormones influence the
      development of the disease. Estrogens provide the protective effects against the
      virus. Progesterone does not modify the body sensitivity to HSV, but reduces the
      effectiveness of the antiviral immunity, resulting in increased mortality of
      animals. We demonstrated that infection of oocytes in ovarian follicles of female
      mice during infection with HSV modified the process in vitro and for the first
      time demonstrated the detection of viral antigens in mature oocytes in patient
      with infertility. During the intracytoplasmic sperm injection into the infected
      oocytes (ICSI), the failure of fertilization was observed. These results are of
      interest, because there is no available literature on whether HSV infection of
      oocytes can have a direct negative impact on the process of fertilization in
      humans.

PMID- 25065147
TI  - [An ultrastructural study of the cervix epitelium infected with the human
      papillomavirus types 16 and 18 before and after treatment with contrasting thermo
      laser therapy].
AB  - The results of the ultrastructural study of the epithelium of the patient cervix
      infected by the human papillomavirus (HPV) types 16 and 18 before and after
      treatment by contrasting thermo-laser therapy (CTLT) are presented. It was shown
      in this work that 1.5 and 6 months after treatment HPV DNA was not detected in
      the biopsy and the smear of the cervix using the polymerase chain reaction (PCR).
      In the ultrathin sections, the structure of the epithelial cells from the biopsy
      after treatment corresponded to norm. There was effective elimination of HPV
      types 16 and 18 as Induces by CTLT method.

PMID- 25065148
TI  - Jails are not healthcare.

PMID- 25065149
TI  - Treatment providers face off against patient advocates over AOT.

PMID- 25065150
TI  - Annual showcase highlights safety, patient flow, and community integration.

PMID- 25065151
TI  - Eliminate curtains from all patient accessible areas.

PMID- 25065152
TI  - Price transparency in healthcare: a movement takes hold.

PMID- 25065153
TI  - To merge, or not to merge.

PMID- 25065154
TI  - Get found. How to leverage local SEO.

PMID- 25065155
TI  - Naloxone auto-injector gains FDA approval.

PMID- 25065156
TI  - ICD-10: the good, the bad, and the advice.

PMID- 25065157
TI  - Mental healthcare without boundaries.

PMID- 25065158
TI  - Kids TLC helps families and children, focusing on trauma and partnerships.

PMID- 25065159
TI  - [The risk of app dependence].

PMID- 25065160
TI  - [Nitrofurantoin--clinical relevance in uncomplicated urinary tract infections].
AB  - The nitrofuran derivative nitrofurantoin has been used for more than 60 years for
      the antibacterial therapy of uncomplicated urinary tract infections (UTI).
      Despite its long application, this antibiotic retained good activity against
      Escherichia coli and some other pathogens of uncomplicated urinary tract
      infections such as Staphylococcus saprophyticus and Enterococcus species.
      Nitrofurantoin therapy has been shown to be accompanied by numerous adverse drug
      effects. Among these, there are also serious side effects such as pulmonary
      reactions and polyneuropathy, which mainly occur in long-term use. Recent
      studies, however, have shown a good efficacy and tolerability of short-term
      nitrofurantoin therapy comparable to previous established standard therapeutic
      regimens applying cotrimoxazole or quinolones. Because of these data and the
      alarming resistance rates of uropathogenic Escherichia coli to cotrimoxazole and
      quinolones that have been increased markedly in several countries, the clinical
      significance ofnitrofurantoin has been raised again. In many current treatment
      guidelines, e. g., the international clinical practice guidelines for the
      treatment of acute uncomplicated cystitis and pyelonephritis in women published
      by the Infectious Diseases Society of America and the European Society for
      Microbiology and Infectious Diseases, nitrofurantoin has been recommended as one
      first-line antibiotic of empiric antibacterial treatment of uncomplicated
      cystitis in otherwise healthy women. In Germany, however, nitrofurantoin should
      only be applied if more effective and less risky antibiotics cannot be used.
      Nitrofurantoin is contraindicated in the last three months of pregnancy and in
      patients suffering from renal impairment of each degree. Despite compatibility
      concerns, nitrofurantoin has also been recommended for the re-infection
      prophylaxis of recurrent uncomplicated urinary tract infections in Germany and
      several other countries.

PMID- 25065161
TI  - [Food supplements--possibilities and limitations: Part 6, Safety and possible
      risks].
AB  - Due to the precautionary principle in consumer protection, thresholds for long
      term safety of nutrients have to be defined. Three toxical indicators are of
      interest: lowest observed adverse effect level (LOAEL); no observed adverse
      effect level (NOAEL) und tolerable level of upper intake (UL). An uptake of a
      nutrient within the range of UL is without side effects even on the basis of long
      term consumption. The UL can be used to derive maximum levels for nutrients in
      food supplements. In general, vitamins can be regarded as safe nutrients except
      for vitamin A. Adverse effects only occur at excessive intake far beyond the
      recommended daily allowances. In contrast, the range of safe intake for minerals,
      especially trace elements, is much smaller. This can be seen clearly in the case
      of selenium. In order to prevent severe selenium deficiency a plasma
      concentration of > 0.25 micromol/l (> 20 microg/l) must be reached. To minimize
      cancer risk a plasma concentration of 1.5 micromol/l (120 microg/l) is needed.
      First signs of selenium intoxications occur at plasma levels over 250 microg/l.
      It is the dose that makes the preventive effect and the poison as well.

PMID- 25065162
TI  - [Taking aspirin for prevention of "traveler's thrombosis"?].

PMID- 25065163
TI  - [Alpha-1-proteinase inhibitor deficiency. Substitution slows degradation of lung
      tissue].

PMID- 25065164
TI  - [Anorexia nervosa in adolescents. Day therapy is not inferior to
      hospitalization].

PMID- 25065165
TI  - [Testosterone deficiency syndrome. Should the safety of testosterone therapy
      questioned?].

PMID- 25065166
TI  - [Safe drug treatment. More communication, enhanced security].

PMID- 25065167
TI  - [Drug information. Drug information service improves patient care].

PMID- 25065168
TI  - [Peanut allergy. Desensitization by oral immunotherapy].

PMID- 25065169
TI  - [Psoriasis. Inhibition of IL-17 signaling pathway by Secukinumab].

PMID- 25065170
TI  - [Chronic Lymphocytic Leukemia. New targeted therapy option Ibrutinib].

PMID- 25065171
TI  - [CHD and heart failure. Heart rate reduction guidelines as a therapy target].

PMID- 25065172
TI  - [Treatment of refractory hypertension. Renal denervation does not meet
      expectations].

PMID- 25065173
TI  - [Hyperlipidemia. New treatment option with Evolocumab].

PMID- 25065174
TI  - [Diabetes mellitus type 1 and 2. Flexible therapy with insulin degludec].

PMID- 25065175
TI  - [Diabetes mellitus type 2 the status of future therapy with GPR40 agonists].

PMID- 25065176
TI  - [Type 2 diabetes mellitus. 15 Years UKPDS].

PMID- 25065177
TI  - [What are the educational needs for the today's health professionals?].

PMID- 25065178
TI  - [Multidisciplinary care of chronic disease].

PMID- 25065179
TI  - [How to decrease the lack of access to care for the very poor].

PMID- 25065180
TI  - [Summer is here again. Reducing the risk of pediatric falls from windows].

PMID- 25065181
TI  - [Putting a stop to sexual harassment in the public sector].

PMID- 25065182
TI  - [Nurses and nurses' aides are the most effected by hospital workplace accidents].

PMID- 25065183
TI  - [Twenty thousand newborns are effected by birth defects each year].

PMID- 25065184
TI  - [Adoption of the 3rd European health program, 2014-2020].

PMID- 25065185
TI  - [How to better protect our health and the health of our children].

PMID- 25065186
TI  - [Development of a blood glucose monitor].

PMID- 25065187
TI  - [An alternative outpatient treatment for rheumatoid arthritis].

PMID- 25065188
TI  - [Outpatient surgery in France in 2014].
AB  - The outpatient surgery is still relatively underdeveloped in France, despite the
      benefits for patients and for hospital teams. The obstacles to its development
      are cultural as well as financial.

PMID- 25065189
TI  - [The organizational model of outpatient care].
AB  - The organisation of outpatient surgical care is centred on patients. The aim is
      to optimise the duration of the stay while assuring the quality of care and
      patient safety. The general principle is that the patient spends the exact amount
      of time necessary at each stage of their treatment.

PMID- 25065190
TI  - [The typical pathway of a patient in short route outpatient surgery].
AB  - The short route is an outpatient surgical unit characterised by immediate
      proximity to the operating theatre. It is an organisational and architectural
      concept in which the patient management aims to be personalised and safe. After
      the procedure, patients are monitored for as long as necessary, as with
      traditional outpatient surgery, before being discharged.

PMID- 25065191
TI  - [Outpatient surgery, the role of the nurse].
AB  - The nurse is a key link in the outpatient surgery pathway. The nurse consultation
      prior to the operation helps to reassure the patient and their family. Her care
      of the patient on the day of the operation and the postoperative education are
      the opportunity for her to fulfil her unique function and educational role.

PMID- 25065192
TI  - [Follow-up of patients at home after outpatient surgery].
AB  - The patient's discharge and return home are important stages in outpatient
      surgery. In addition to the call the following day and the support of a family
      caregiver, a visit by a private practice nurse and a healthcare network can offer
      extra safeguards.

PMID- 25065193
TI  - [The ethical reflection approach, a source of wellbeing at work].
AB  - Clinical nursing practice, beyond its application to care procedures, can be
      expressed in terms of ethical added value in the support of patients. In Reims
      university hospital, where a clinical ethics and care think-tank was created in
      June 2010, the ethical reflection approach is encouraged in order to reemphasise
      the global meaning of care as a source of wellbeing at work.

PMID- 25065194
TI  - [Fostering compliance by understanding its mechanisms].
AB  - In the context of chronic disease, nurses play an essential role in the long-term
      support of the patient. The therapeutic alliance which they create with the
      patient enables them to detect the various factors which influence compliance, or
      on the contrary, the non-compliance of the patient. They work in a context of
      interdisciplinarity in a collaborative practice in which the patient is a
      partner. Their interventions aim to support the patient in adopting the right
      health strategies.

PMID- 25065195
TI  - [Cognitive disorders, new demands for individualized home care].
AB  - In their homecare practice, healthcare professionals and professional caregivers
      take a global approach to persons with cognitive disorders and their family.
      Beyond the health and domestic aspects, new needs are being expressed in the area
      of social and leisure activities.

PMID- 25065196
TI  - [Enriching patient care with aromatherapy].
AB  - There are increasing numbers of initiatives in healthcare institutions focusing
      on the benefits of essential oils. Received positively by patients who appreciate
      the resulting wellbeing, these innovative approaches around aromatherapy are
      based on the initiative of pioneering caregivers. Following on from an
      international congress held each year in Grasse, this article presents some
      example schemes.

PMID- 25065197
TI  - [Nursing care of the stoma patient].

PMID- 25065198
TI  - [The nurse and disaster planning].

PMID- 25065199
TI  - An epileptic seizure on a flight.

PMID- 25065200
TI  - [Auto-injector needles: calculation and surveillance].

PMID- 25065202
TI  - [A case of transfusion-transmitted falciparum malaria].

PMID- 25065201
TI  - [Cerebrospinal fluid diversion].

PMID- 25065203
TI  - [Progress and challenges of the National Schistosomiasis Control Program during
      the period of the 12th Five-Year Plan].
AB  - The achievements of the national schistosomiasis control program during the
      period of the 12th Five-Year Plan were reviewed, in particular, the reduction of
      the prevalence and progress in control activities were evalucated among different
      regions of China. Moreover, current difficulties of schistosomiasis control and
      gaps to achieve the transmission interruption of the disease in China were
      analyzed, which provide more evidences to formulate the future efforts and work
      plan to eliminate the disease in the country.

PMID- 25065204
TI  - [Prokaryotic expression and function analysis of Schistosoma japonicum calpain].
AB  - OBJECTIVE: To clone and express recombinant calpain of Schistosoma japonicum
      (Sjcalpain), observe the distribution of Sjcalpain in S. japonicum cercariae and
      analyze its role in skin invasion. METHODS: The primers were designed according
      to the full-length sequence of calpain (GenBank accession No. AB016726). The
      genes encoding catalytic domain and Ca2+ binding domain of Sjcalpain were
      amplified by PCR, and the target fragments were subcloned into pET-28a. The
      recombinant proteins were expressed in E. coli BL21 (DE3) and purified by Ni-NTA
      resin. The rabbit polyclonal antibodies were prepared with the two purified
      recombinant proteins by immunizing New Zealand white rabbits. ELISA was used to
      detect the titer of rabbit antiserum. Immunolocalization was used to investigate
      the distribution of Sjcalpain in S. japonicum cercariae. Cercariae were incubated
      with specific inhibitor before infection of mice and the worm reduction rate was
      calculated. RESULTS: The recombinant expression vector Sjcalpain catalytic
      domain/pET28a and Sjcalpain Ca2+ binding domain/pET28a were constructed and the
      recombinant proteins were successfully expressed in E. coli BL21 (DE3) (about
      M(r) 43 000 and M(r) 39 000, respectively). The two target proteins were
      expressed as inclusion bodies. The purified target proteins were obtained through
      Ni-NTA affinity purification. ELISA result showed that the titer of prepared
      rabbit polyclonal antibodies was higher than 1 : 80 000. Immunolocalization study
      demonstrated that Sjcalpain protein was mainly expressed in the head of
      cercariae. Inhibition assays suggested that the average number of adult worms in
      calpain inhibitor-incubation group and control group was 19 and 23, respectively,
      with a worm reduction rate of 17.4%. CONCLUSION: Sjcalpain is mainly expressed in
      the head of S. japonicum cercariae. Inhibition of Sjcalpain could reduce the
      number of invading cercariae in infected mice, which suggest that Sjcalpain may
      play a role in skin invasion by cercariae.

PMID- 25065205
TI  - [Hemocyte morphology and classification in Oncomelania hupensis].
AB  - Hemocytes were collected from Oncomelania hupensis in Junshan, Hunan Province and
      Puge, Sichuan Province, respectively, and stained with Giemsa solution for light
      microscopic examination. The cells were classified morphologically. Five types of
      hemocytes were identified, viz., large acidophilic hyalinocytes, small
      acidophilic hyalinocytes, basophilic hyalinocytes, basophilic small granulocytes
      and basophilic large granulocytes. The proportion of small acidophilic
      hyalinocytes was the most abundant hemocyte [36.7% (229/624) in snails from
      Junshan and 31.7% (257/810) in snails from Puge], followed by basophilic
      hyalinocyte [23.1% (144/624) in Junshan and 24.4% (198/810) in Puge]. Basophilic
      large granulocyte was about 9.3% (58/624) in Junshan and 11.6% (94/810) in Puge.
      The length of large acidophilic hyalinocytes was the maximum and its
      nucleocytoplasmic ratio was minimum, followed by small acidophilic hyalinocytes.
      The length of basophilic cells was shorter and its nucleocytoplasmic ratio was
      smaller than those of acidophilic cells. There was no significant difference in
      cellular constituents of hemocytes and the morphological features of hyalinocytes
      between the snails from Junshan and Puge, while the length and nucleocytoplasmic
      ratio of granulocytes in Junshan snails were smaller than those of Puge ones.

PMID- 25065206
TI  - [Cloning, expression and transcription specificity analysis of two tyrosinases
      from Schistosoma japonicum].
AB  - OBJECTIVE: To clone and express the recombinant proteins based on the whole open
      reading frame of two tyrosinases (tyrosinase 1 and tyrosinase 2) from Schistosoma
      japonicum, and study the transcription specificity of the two tyrosinases in
      different sex and developmental stages of S. japonicum. METHODS: The full-length
      of SjTYR1 and SjTYR2 were amplified with specific primers and subcloned into
      pSJ2. The recombinant plasmids were transformed into E. coli Rosetta Gami strains
      and induced with IPTG for expression. The recombinant proteins were purified by
      Ni-NTA agarose. The recombinant proteins SjTYR1 and SjTYR2 were used to produce
      the specific antibodies by immunizing the rabbits. The immunogenicity of the
      recombinant proteins SjTYR1 and SjTYR2 were detected by Western blotting using
      sera of recombinant proteins-immunized rabbits and S. japonicum-infected rabbit
      serum as the primary antibody, respectively. The reactivity of sera from
      recombinant proteins-immunized rabbits was analyzed by Western blotting against
      the native protein of S. japonicum worm. Total RNA was extracted from 14, 16, 18,
      20, 22, 24, 26, and 28-day male and female worms. Transcription levels of the two
      tyrosinases in different sex and different stage were determined via RT-PCR
      method. RESULTS: The expression vector of SjTYR1/pSJ2 and SjTYR2/pSJ2 were
      constructed and the recombinant pro teins SjTYR1 and SjTYR2 were expressed in
      inclusion body in E. coli (about M(r) 55 000 and M(r) 56 800). The sera of S.
      japonicum-infected rabbits reacted positively with the purified recombinant
      protein SjTYR1, but not with recombinant protein SjTYR2. The native protein of S.
      japonicum worm could be recognized by sera of rSjTYR1-immunized rabbits (M(r) 100
      000), but not by sera of rSjTYR2-immunized rabbits. Transcription levels of the
      two tyrosinases in male worms were nearly zero. In female worms, the
      transcription levels of the two tyrosinases increased sharply from the 24th day
      post-in- fection and reached maximum on the 28th day. CONCLUSION: The recombinant
      proteins of SjTYR1 and SjTYR2 show immunogenicity and immunoreactivity. SjTYR1
      and SjTYR2 are both expressed specifically in female worms and the transcription
      levels increase in 24-28 days after infection.

PMID- 25065207
TI  - [Expression of Toll-like receptors 2 and 6 in mice liver during Schistosoma
      japonicum infection].
AB  - OBJECTIVE: To investigate the expression of hepatic Toll-like receptor 1 (TLR1),
      TLR2 and TLR6 on mice with Schistosoma japonicum infection. METHODS: Fifty BALB/c
      mice were infected with 20 +/- 3 S. japonicum cercariae through abdominal skin.
      At 6 weeks post-infection, the mice (n = 10) in treatment group were administered
      intragastrically with praziquantel [250 microg/(g x d)] for 3 d. The livers of
      mice (n = 10) were collected at pre-infection and 5, 6, 8 and 12 weeks post
      infection, and then the mRNA expression levels of hepatic TLR1, TLR2, TLR6 gene
      were detected with reverse transfer PCR. Hepatic TLR2, TLR6 protein levels were
      detected by immunohistochemical staining. RESULTS: The mRNA levels of TLR1, TLR2,
      and TLR6 on 5, 6, 8 and 12 weeks post infection were significantly higher than
      that of uninfected mice. After praziquantel treatment, the mRNA level of TLR2 and
      TLR6 in murine liver of treatment group was lower than that of infection group,
      but the level of TLR1 mRNA had no obvious change. Furthermore,
      immunohistochemistry results revealed that the expression of TLR2 and TLR6
      proteins in murine liver was up-regulated at 5, 6, 8 and 12 weeks post-infection.
      After praziquantel treatment, the percentage of TLR2 positive area in liver of
      infected mice without and with praziquantel treatment were (44.2 +/- 4.3)%, (8.8
      +/- 3.1)%, respectively, and TLR2 protein level was considerably down-regulated
      (P < 0.01). The percentage of TLR6 positive area in liver of infected mice
      without and with praziquantel treatment was (48.4 +/- 5.4)%, (37.4 +/- 3.5)%,
      respectively, and TLR6 level decreased slightly (P < 0.05). CONCLUSION: The
      expression level of TRL2 and TLR6 in murine liver increases after Schistosoma
      japonicum infection. While compared with TLR2, the role of TLR6 in this progress
      is a weaker one.

PMID- 25065208
TI  - [Changes of IFN-gamma, IL-4 and T cells in Schistosoma japonicum-infected mice
      after praziquantel treatment].
AB  - OBJECTIVE: To investigate the serum levels of IFN-gamma and IL-4, and the dynamic
      changes of IFN-gamma-specific and IL-4-specific lymphocytes in mice with
      Schistosoma japonicum infection after treatment by praziquantel. METHODS: Ninety
      BALB/c mice were randomly divided into three groups (n = 30) named as infection
      group, treatment group and control group. The mice in treatment group and
      infection group were infected with (25 +/- 2) S. japonicum cercariae through the
      abdominal skin. At 6 weeks post-infection, the mice in treatment group were
      administered orally with praziquantel [300 mg/(kg x d)] for 3 d. At 4, 6, 8 and
      12 weeks post-treatment, the mice were weighed, and serum samples were collected.
      Serum levels of IFN-gamma and IL-4 were measured by ELISA. At the same time, the
      spleens were aseptically removed to prepare cell suspension, and the counts of
      IFN-gamma and IL-4 specific lymphocytes were examined by ELISPOT after
      stimulation of Schistosoma japonicum soluble egg antigen (SEA). RESULTS: From 4
      to 12 weeks after praziquantel treatment, the body weight of mice in treatment
      group were significantly heavier than that of infection group (P < 0.05), but no
      significant difference was found between treatment group and control group (P <
      0.05). At 4 weeks posttreatment, there was no significant difference in serum
      levels of IFN-gamma and IL-4 between treatment group and infection group (P >
      0.05). At 6, 8, and 12 weeks after treatment, the serum levels of IFN-gamma
      (0.038 +/- 0.013, 0.028 +/- 0.001, and 0.027 +/- 0.007) and IL-4(0.051 +/- 0.020,
      0.045 +/- 0.019, and 0.043 +/- 0.016) in treatment group were significantly lower
      than that of infection group (IFN-gamma: 0.057 +/- 0.004, 0.060 +/- 0.023, and
      0.052 +/- 0.017; IL-4: 0.150 +/- 0.014, 0.148 +/- 0.014, and 0.123 +/- 0.017) (P
      < 0.05). Serum IFN-gamma and IL-4 levels in treatment group and infection group
      were significantly higher than that of control group (P < 0.05). ELISPOT results
      showed that at 4, 6 weeks post-treatment, there was no significant difference in
      the number of IFN-gamma-specific lymphocytes between treatment group and
      infection group (P > 0.05). While at 8 and 12 weeks after treatment, the IFN
      gamma-specific lymphocytes in treatment group (39.9 +/- 22.8 and 38.5 +/- 6.2)
      were significantly less than that of infection group (141.9 +/- 39.3 and 106.8 +/
      28.6) (P < 0.05). At 4-week post-treatment, the IL-4-specific lymphocytes in
      treatment group were much more than that of infection group (175.6 +/- 62.3) (P <
      0.05), and then began to decline. At 8 and 12 weeks after treatment, the IL-4
      specific lymphocytes (111.3 +/- 14.3 and 113.0 +/- 44.2) in treatment group were
      significantly less than that of infection group (220.3 +/- 107.1 and 208.1 +/-
      17.2) (P < 0.05). The IFN-gamma-specific and IL-4-specific lymphocytes in
      treatment group and infection group were significantly more than that of control
      group (P < 0.05). CONCLUSION: After praziquantel treatment, the serum levels of
      IFN-gamma and IL-4 in mice with S. japonicum infection decrease, and the number
      of IFN-gamma and IL-4 specific lymphocytes reduces.

PMID- 25065209
TI  - [Application of space-time scan statistics in the analysis of spatial and
      temporal distribution of Oncomelania hupensis snails in Gaoyou County, Jiangsu
      Province].
AB  - OBJECTIVE: To investigate the distribution features of Oncomelania hupensis
      infested areas in Gaoyou County so as to formulate surveillance and intervention
      strategies. METHODS: A database was established through collecting data of the
      snail infested areas during 1970-2009 in the County. The data were input into
      SaTScan 9.2 software for spatial-temporal cluster analysis to determine the
      spatial and temporal cluster of the snail habitats. The results were displayed by
      ArcGIS 10.1 software. RESULTS: There were historically 720 snail habitats in the
      County in 1970-2009 including 521 in plain region with water networks and 199 in
      lake & marshland region. Those in water networks covered an area of 456.62 ha
      distributing mainly in the northern towns/townships of the County, and the
      latters distributed in the Xinmin Beach between Gaoyou Lake and Shaobo Lake, and
      Qiaojian Beach close to Tianchang County of Anhui Province with an area of 4
      495.75 ha. The spatial-temporal cluster analysis revealed that among all the
      historical snail habitats, there were two prominent spatial-temporal clusters
      with a relative risk of >3. One cluster appeared in Xinmin Beach in 1983-2002 and
      another one located in the north of Gaoyou in 1970-1973. Separate analysis was
      performed by the regions of water network or lake & marshland, indicating 2
      clusters in each of the regions. During 1970-2009, 244 snail habitats were newly
      found in the County with 130 in water network region and 114 in lake & marshland
      region. Again, the spatial-temporal cluster analysis displayed 2 prominent
      clusters. By separate analysis, 2 clusters existed in each of the regions.
      CONCLUSION: The space-time scan statistics can be applied in detecting the
      cluster of snail infested areas in two dimensions, which will provide information
      for guiding specific measures of surveillance and control.

PMID- 25065210
TI  - [Diagnostic potential of five natural antigens from Echinococcus granulosus in
      the patients of cystic echinococcosis with different clinical status].
AB  - OBJECTIVE: To analyze the characteristics of serum antibody reactivity of cystic
      echinococcosis (CE) patients with different clinical status towards five native
      antigens obtained from Echinococcus granulosus (Eg). METHODS: The protoscolex
      somatic soluble antigen (EgPS), crude hydatid cyst fluid antigen (EgHF),
      partially purified hydatid fluid antigen (Burstein's antigen, EgBu), adult
      somatic soluble antigen (EgAs) and the native antigen B (EgAgB) were pre- pared.
      369 serum samples from CE patients and 281 sera samples from healthy individuals
      were examined for the antibodies against 5 native antigens with indirect ELISA.
      The serologic results were classified according to clinical status, and the
      statistical analyses were carried out to understand the relationship between the
      results of different antigen-ELISA and the clinical status of patients. RESULTS:
      The results of EgBu, EgAS and EgAgB-ELISA showed that the antibody positive rate
      in hepatic CE patients [74.1% (212/286), 73.4% (210/286), 63.6% (182/286)] was
      significantly higher than that of other groups (including renal CE and pelvic CE,
      1/8, 2/8, 1/8) (P < 0.05). Except EgAS, the S/N value of other groups examined by
      the rest four antigen-ELISA (EgPS: 3.10, EgHF: 2.40, EgBu: 1.60, EgAgB: 2.38) was
      also significantly lower than that of hepatic CE patients (3.73, 3.65, 4.40, and
      3.61) (P < 0.05). EgBu, EgAS and EgAgB-ELISA results showed that the antibody
      positive rate in sera of recurrent CE patients [82.4% (150/182), 86.3% (157/182),
      70.9% (129/182)] and the S/N value (5.54, 3.23, 3.75) were significantly higher
      than that of primary patients [positive rate: 67.4% (126/187); 63.6% (119/187);
      57.2% (107/187); S/N value: 4.20, 2.70, 3.75] (P < 0.05). The S/N value detected
      by EgPS-ELISA and the positive rate examined by EgAgB-ELISA significantly
      increased with the increasing of the number of operations (P < 0.05), reached
      4.23 and 91.7% (11/12), respectively, in the patients with > or = 4 times of
      operations. The positive rate and S/N value of EgAS-ELISA and EgAgB-ELISA
      increased with the number of hydatid cysts in patients (P < 0.05), reached 90.5%
      (19/21), 76.2% (16/21), and 3.97, 4.42, respectively, in patients with at least 4
      cysts. Among the five antigen-ELISA, the positive rate increased with the cyst
      diameter (P > 0.05). The S/N value of EgHF-ELISA and EgAS-ELISA increased
      significantly with the cyst diameter (P < 0.05), reached 3.66 and 3.69,
      respectively, when the cyst diameter was > or = 15.1 cm. ROC analysis result
      showed that among the 5 native antigen-ELISA, the AUC(ROC) was highest in
      patients with cysts at CE2 stage (EgPS: 0.988 +/- 0.009, EgHF: 0.957 +/- 0.013,
      EgBu: 0.969 +/- 0.011, EgAs: 0.910 +/- 0.024, EgAgB: 0.894 +/- 0.021), EgAgB
      ELISA presented the lowest AUC(RCO) of 0.267 +/- 0.031 in patients with cysts at
      CE5 stage. Except EgAgB, the positive rate of another 4 antigen-ELISA in
      detection of patients with cysts at CE 2 stage [EgPS: 97.2% (69/71), EgHF: 93.0%
      (66/71), EgBu: 88.7% (63/71), EgAs: 85.9% (61/71)] was slightly higher than that
      of the patients with cysts at CE1 stage, and then promptly reduced in patients
      with cysts at CE5 stage (EgPS: 56.3%, EgHF: 43.8%, EgBu: 12.5%, EgAs: 12.5%). In
      the patients with cysts at CE5 stage, the S/N value of the five antigen-ELISA was
      lowest (EgPS: 2.29, EgHF: 1.50, EgBu: 1.11, EgAs: 0.78, and EgAgB: 1.11).
      CONCLUSION: Compared with the other three antigens, the EgPS and EgAgB antigens
      have higher antigenicity, sensitivity, and specificity. The sera of hepatic CE
      patients are more reactive to the five native antigens than the other clinical
      types.

PMID- 25065211
TI  - [Effect of culture supernatant of Toxoplasma gondii on the proliferation and
      apoptosis of BGC-823 cells].
AB  - OBJECTIVE: To investigate the effect of culture supernatant of Toxoplasma gondii
      on the proliferation and Toxoplasma gondii tachyzoites with seed counts of 2 x
      10(7)/ml, apoptosis of human gastric cancer BGC-823 cells. METHODS: 4 x 10(7)/ml,
      and 8 x 10(7)/ml harvested from infected mice were cultured for 24 h, and then
      the culture supernatant was collected. BGC-823 cells (5 x 10(4)/ml) at mid
      exponential phase were incubated with different concentrations of culture
      supernatants of Toxoplasma gondii tachyzoites. While in control group, the same
      volume of DMEM was given. At 24, 48 and 72 h after incubation, the measurement of
      tumor cell growth inhibition rate was performed by using CCK-8 kit. Cell
      apoptosis was observed under a fluorescence microscope after 24 h incubation. The
      DNA ladder zone of apoptosis cells was analyzed with the method of agarose gel
      electrophoresis. Flow cytometric analysis was used to analyze cell cycle for cell
      proliferation index and the expression of p53 and Bcl-2. RESULTS: The culture
      supernatant of Toxoplasma tachyzoites inhibited the proliferation of BGC-823
      cells and the growth inhibition rates increased with the time and the
      concentration. The highest rate reached at the 72nd hour when the concentration
      of Toxoplasma tachyzoites was 8 x 10(7)/ml. Apoptotic bodies were found in
      experimental group. The amount of apoptotic body was positively associated with
      the tachyzoite concentration. DNA fragment in the treated cells after 24 h
      incubation was revealed by agarose electrophoresis. When the proportion of BGC
      823 cells in G0/G1 phase increased, the proportion of cells in S phase decreased.
      Cell proliferation index decreased with the increase of the concentration of
      tachyzoites. The proliferation index (0.36) of the cells cultured with culture
      supernatant of 8 x 10(7)/ml tachyzoites was significantly lower than that of
      control group (0.6, P < 0.05). p53 protein expression was higher in experiment
      group than that of the control, whereas Bcl-2 protein expression in experiment
      group was lower than that of the control (P < 0.05). CONCLUSION: The culture
      supernatant of Toxoplasma gondii can inhibit the proliferation of BGC-823 cells
      and cause apoptosis of BGC-823 cells, which may be related with up-regulating p53
      expression and down-regulating Bcl-2 expression.

PMID- 25065212
TI  - [Resistance of Anopheles sinensis to three common insecticides in Hainan
      Province].
AB  - Anopheles sinensis adults were collected by cow-baited trap in Haikou City, Sanya
      City, Lingshui County, Changjiang County and Qiongzhong County of Hainan Province
      during 2011-2013. The mosquitoes were exposed to insecticide impregnated papers
      with discriminating concentrations of DDT (4%), deltamethrin (0.05%), and
      malathion (5%) using WHO standard assays. Knockdown rate was recorded at 10, 15,
      20, 30, 40, 50, and 60 min, and KT50 values were calculated. Mortality was
      recorded after 24 hours of exposure. The resistance level was graded as sensitive
      group (S) with a mortality rate of 98%-100%, preliminary resistance group (M)
      with mortality rate of 80%-97%, and resistance group (R) with mortality rate of
      lower than 80%. The results showed that the mortality rate of An. sinensis in
      Qiongzhong County in 24 h-post-exposure to 0.05% deltamethrin was 95.0% with a
      resistance degree of M. That to 0.05% deltamethrin in the other 4 sites was 17.0%
      63.0%, all with a resistance degree of R. That to 4% DDT in Haikou, Sanya,
      Lingshui, Qiongzhong and Changjiang was 36.0%, 27.0%, 24.0%, 59.1%, and 82.0%,
      with a resistance level of R, R, R, R, and M, respectively. That to 5% malathion
      in Haikou, Sanya, and Lingshui was 16.0%-41.0%, all with a resistance degree of
      R, while that to malathion in Qiongzhong and Changjiang was 100% and 98.0%,
      respectively, with a resistance level of S.

PMID- 25065213
TI  - [Preparation and application of the polyclonal antibody of Toxoplasma gondii
      autophagy protein 8 (TgAtg8)].
AB  - OBJECTIVE: To prepare and evaluate specific-TgAtg8 polyclonal antibody. METHODS:
      The known Saccharomyces cerevisiae Atg protein sequences were used to identify
      Toxoplasma gondii homologous protein through bioinformatics analysis. TgAtg8 cDNA
      was amplified and cloned into prokaryotic expression vector pGEX-6p-1. The
      constructed pGEX-6p-1-TgAtg8 was transformed into E. coli BL21 cells and induced
      with IPTG for expression. The expression product was analyzed through SDS-PAGE
      and Western blotting. The recombinant TgAtg8 protein with an N-terminal
      glutathione-S transferase tag was used to immunize rabbits and raise specific
      polyclonal antibody against TgAtg8. Subsequently, the antibody was applied for
      Western blotting and IFA assay. RESULTS: Recombinant expression plasmid of pGEX
      6p-1-TgAtg8 was confirmed correct by restriction enzyme digestion and sequencing.
      SDS-PAGE and Western blotting analysis showed that the recombinant TgAtg8 protein
      with the predicted molecular weight (M(r)40000) was expressed highly in E. coli
      BL21. After immunization, the specific antibodies against TgAtg8 protein were
      produced. The anti-TgAtg8 polyclonal antibody reacted specifically with TgAtg8
      fusion protein or endogenous TgAtg8. Importantly, IFA assay determined that the
      TgAtg8 signal was generally distributed throughout the cytoplasm of the
      tachyzoites. However, the green fluorescence signal gathered into one or more
      green spots after induction of autophagy. CONCLUSION: The specific polyclonal
      antibody against TgAtg8 could be used to observe the dynamics of autophagosome
      formation in T. gondii, which is useful tool to investigate the autophagic
      machinery in this parasite.

PMID- 25065214
TI  - [Effect of diets with different fat levels on the body size and development of
      Lucilia sericata].
AB  - OBJECTIVE: To observe the effect of diets with different fat levels on the body
      size and development of Lucilia sericata. METHODS: Under the constant temperature
      of 28 degrees C, the larvae were reared on the diets containing 0% (G0), 10%
      (G1), 30% (G3), 50% (G5) and 80% (G8) fat tissues (fat/muscle ratio),
      respectively. Length and weight of larvae and pupae were measured at 12 h
      interval since 16 h after eclosion. Length of inter-medial cross vein (m-m) of
      adult left wing was measured. 10 samples were collected in each group. The
      developmental duration time, mortality and sex ratios of adults were recorded.
      RESULTS: The mean maximal larval length [(13.3 +/- 1.2), (12.0 +/- 1.1), (10.2 +/
      0.9) and (8.8 +/- 0.8) mm, respectively] and mean maximal larval weight [(72.8
      +/- 6.1), (62.2 +/- 5.7), (47.2 +/- 4.3), and (34.9 +/- 5.7) mg] in G1, G3, G5
      and G8 groups were significantly less than that of the G0 group [(14.8 +/- 1.3)
      mm and (80.4 +/- 8.1) mg](P < 0.01). The body size of pupae and adults was also
      significantly less than that of G0 group (P < 0.01). The total duration time of
      G5 and G8 groups [(293.3 +/- 22.2) and (285.2 +/- 24.6) h] were significantly
      shorter than that of G0 group [(312.8 +/- 20.1)h] (P < 0.01). The mortality of
      larvae [(32.6 +/- 5.6)% and (44.3 +/- 7.7)%] and pupae [(28.6 +/- 5.5)% and (43.5
      +/- 6.2)%] of G5 and G8 group were also significantly higher than that of G0
      group [(5.7 +/- 3.3)% and (4.5 +/- 1.9)%] (P < 0.01). There was no significant
      difference in sex ratio among the 5 groups (P > 0.05). CONCLUSION: The body size
      of larvae, pupae and adults of Lucilia sericata is smaller, the development time
      is shorter and mortality is higher when the food substrate contains more fat
      tissues.

PMID- 25065215
TI  - [Preliminary survey on the host of Angiostrongylus cantonensis in three plateau
      lakes of Yunnan Province].
AB  - OBJECTIVE: To investigated the intermediate hosts of Angiostrongylus cantonensis
      in three plateau lakes of Yunnan Province, and analyze the effect of temperature
      on A. cantonensis during 1991-2010. METHODS: An epidemiological investigation of
      angiostrongyliasis cantonensis in Erhai Lake, Fuxian Lake and Xingyun Lake was
      conducted from April to September in 2012. Snails were examined for the third
      stage larvae by enzyme digestion or lung examination. Rodents were captured in
      the fields, and their hearts and lungs were dissected for adult worms. The
      potential distribution of A. cantonensis and its main intermediate host Pomacea
      canaliculata were predicted based on degree-day models using GIS technique.
      RESULTS: A total of 4 950 snails were collected, belonging to 4 species, P.
      canaliculata, Cipangopaludina chinensis, Bellamya aeruginosa, and B. quadrata.
      174 rodents were captured, belonging to 5 species. No positive samples were
      found. The potential distribution map showed that the distribution of A.
      cantonensis and P. canaliculata in Yunnan would expand with the rise of
      temperature, and with the passage of time they could complete one generation in
      the region which couldn't finish one generation in one year along with time
      passing. CONCLUSION: A. cantonensis are not found in the hosts. The natural
      environment and ecological system of the three lakes match the condition of A.
      cantonensis transmission.

PMID- 25065216
TI  - [Progress of CD8+ T cell-mediated immune response to Toxoplasma gondii
      infection].
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite, which infects
      warm-blooded animals including humans. T. gondii infection in the immune
      competent individual is largely asymptomatic, but it can cause severe
      toxoplasmosis in immune-deficiency patients. T cell-mediated immunity plays an
      important role in resistance against T. gondii. Therefore, this review focuses on
      the progress of CD8+ T cell-mediated immune response to T. gondii infection.

PMID- 25065217
TI  - [The role of CD4+CD25+ regulatory T cells in helminth infection immunity].
AB  - Regulatory T cells (Tregs), a class of CD4+ T lymphocytes which are different
      from the Th1 and Th2 lymphocytes, have immunosuppressive function and play an
      important role in maintaining immune homeostasis and immune tolerance. Previous
      studies showed that the generation of Tregs could be induced, and Tregs reduced
      the immune pathological damage to the host by inhibiting T-cell function in
      helminth infection.

PMID- 25065218
TI  - [Immunity to parasitic infection: the role of dendritic cells].
AB  - Dendritic cells are a major class of professional antigen-presenting cells which
      play an important role in the immune response of parasite-infected host. This
      article summarizes the role of dendritic cells in the immunity to parasitic
      infection by analyzing the studies of protozoan, nematode, and trematode
      infections.

PMID- 25065219
TI  - [Diagnosis of the first imported case of Plasmodium ovale infection at Guangdong
      Port].
AB  - The first imported case of Plasmodium ovale infection in Guangdong Province was
      identified. The patient worked in Myanmar for one week and had a fever when he
      arrived at Guangzhou Baiyun International Airport. Epidemiological information
      and blood sample were collected. The detection was conducted by microscopy, right
      VIEW rapid malaria test (RDTs) and real-time PCR with Plasmodium genus-specific
      and species-specific primers and probes. The case showed weak positive RDT
      result, and was confirmed as P. ovale infection by microscopy and real-time PCR.
      After treatment with artemether, his symptoms improved.

PMID- 25065220
TI  - [Retrospective analysis of granted projects of the National Institute of
      Parasitic Disease, China CDC during 2002-2012].
AB  - In this paper, the granted projects of the National Institute of Parasitic
      Diseases (NIPD), China CDC, was analyzed. The results showed that from 2002 to
      2012, 126 projects were granted to NIPD. 28.6% (36/126) of the projects were at
      the national level; 27% (34/126) were at provincial and ministrerial level.
      International cooperation projects and those supported by state key laboratory
      and enterprises accounted for 28.6% (36/126) and 15.8% (20/126), respectively. 94
      projects belonged to applied researches and 32 belonged to basic researches. Most
      project leaders were young and middle-aged researchers with senior professional
      titles.

PMID- 25065221
TI  - [Investigation on Lophomonas blattarum infection in Periplaneta americana in
      Wuhan City].
AB  - An investigation of Lophomonas blattarum infection in Periplaneta americana in
      Wuhan City were conducted. A total of 110 P. americana were dissected and the
      intestines were separated. The intestines were washed with 0.6% saline and the
      washing solutions were smeared on slides. The slides were stained with Giemsa
      stain and observed under a microscope (x1000). Out of 110 intestine washing
      solution samples, 44 were suspected of L. blattarum infection. The parasite was
      oval or pyriform in shape and 20-40 microm in size. A tuft of flagella extended
      down the central axis of the parasite and a trumpet-shaped calyx enveloped the
      flagellar area and the nucleus. An axostyle was slender and pointed posterior
      ends. Based on the above morphological characteristics, the parasite was
      identified as L. blattarum. The results showed that the infection rate of L.
      blattarum in P. amerivana in Wuhan City was 40.0% (44/110).

PMID- 25065222
TI  - [Survey on intestinal nematode infections among school students in Tengchong
      County].
AB  - One primary school and one middle school were selected from Gudong Town, Tengyue
      Town and Puchuan Township of Tengchong County, respectively, by using the
      lamination stochastic group sampling method. The intestinal parasite infections
      were investigated with the iodine-stained direct smear method and modified Kato
      Katz thick smears method. A total of 1 134 students were investigated and the
      total infection rate of intestinal nematodes was 12.4% (141/1 134). The infection
      rate of Ascaris lumbricoides, Trichuris trichura, and hookworm was 9.4% (106/1
      134), 2.8% (32/1 134), and 0.3% (3/1 134), respectively. The prevalence of
      intestinal nematodes among the students of urban (2.2%, 8/363) was lower than
      those of rural (17.3%, 133/771) (P < 0.01). The infection rate in students from
      Gudong Town was higher than those of Tengyue (2.2%, 8/363) and Puchuan County
      (2.3%, 8/35) (P < 0.01), whereas the economy level of Gudong Town (29.9%,
      123/412) was the best in the three towns. After all, the infection rate of the
      middle school students (13.7%, 59/432) was higher than that of pupils (11.7%,
      82/702) (P < 0.01). Compared with 2003, the prevalence of nematode infection
      among the school students in Tengchong County decreased significantly in 2013.

PMID- 25065223
TI  - [Composition and seasonal fluctuation of acaroid mite communities in warehousing
      environment of northern Anhui Province].
AB  - Samples of stored products were collected every month in 2012 in northern Anhui
      Province. Acaroid mites were isolated, identified and counted. Among 1 440
      samples, 692(48.1%) had mite infestation and 34 species were identified, and the
      density was 32.1 mites/g. The species richness index (R(margalef)) ranged from
      0.48 to 3.30, which was highest in August. The species diversity index (H') was
      1.29-3.32, highest in July. The species evenness index (J) ranged from 0.91 to
      0.97, highest in March. The number of species, breeding density, species richness
      index and species diversity index were stable in the year, while the species
      evenness index showed irregular change. There were many species of acaroid mites
      in the storage circumstance. The composition of acaroid mites were diverse, and
      changed with the seasons.

PMID- 25065224
TI  - [Managing elderly health care costs: one of the challenges of the 21st century ].

PMID- 25065225
TI  - [The role of the geriatrician in the organization of the health care system].
AB  - The purpose of this paper is to define the role of the geriatrician in the
      organization of the health care for the elderly. In Belgium, the healthcare
      program for the geriatric patient defines the various functions; at present, the
      classical geriatric hospitalization, the hospital day care, and the internal
      links within the hospital are well developed around the geriatrician. The
      standardized, comprehensive geriatric assessment of hospitalized patients has
      demonstrated its value for the prevention of functional decline. The efficiency
      of the day care services and of the link teams remains to be further appraised.
      Outside the hospital, the general practionner plays the major role in the
      treatment of the elderly living at home, or in nursing homes. The demographic
      evolution and the frailty of the elderly require a good coordination of all those
      involved in the care of the aged. A model of healthcare organization is proposed
      to better coordinate the in- and out of hospital activities.

PMID- 25065226
TI  - [Screening for frailty: a benefit for both patients and physicians].
AB  - Preventing the increasing number of depending persons is a novel priority in
      European Union health policy. One of the means to succeed relies on identifying,
      among elderly persons, those at risk of dependency, also named "the frail
      elderly". Screening for frailty is also useful to better assess the physiological
      reserves of the elderly before any therapeutic decision, as early as the first
      consultation. Researchers currently work on developing a new simple tool allowing
      a distinction between frail and robust persons. Since frailty is partly
      reversible, the global geriatric evaluation, in a one-day clinic, will lead to a
      personalized program to prevent or reverse frailty by a multidisciplinary
      approach.

PMID- 25065227
TI  - [Nutrition in the elderly].
AB  - Ageing of the body predisposes to a high incidence of undernutrition in the
      elderly person wherever he or she is living, but the prevalence of malnutrition
      is particularly high in hospitalized or instutionalized patients. Early detection
      of malnutrition is important because malnutrition may have significant
      consequences and evaluation of nutritional status has to be a routine screening
      in the elderly. There is no single parameter which supplies a full assessment of
      the patient's nutritional status. It is then necessary to use screening tools for
      the identification of patients at nutritional risk, based on anamnestic,
      antropometric and biological data. The MNA (Mini Nutritional Assessment) test is
      a simple, non invasive, well-validated screening tool for malnutrition in the
      elderly and is recommended for early detection of risks of malnutrition. Numerous
      conditions in relationship with physiological ageing, comorbidity, polymedication
      and the way of life of the individual predispose to undernutrition. Healthy
      nutrition in older patients should respect the guidelines for protein and energy
      requirements, excepted in severely ill patients and/or in case of malnutrition in
      which case the protein-energy intake should be increased.

PMID- 25065228
TI  - [Sarcopenia: what's new in 2014].
AB  - The term "sarcopenia" was first introduced in 1989 by Irwin Rosenberg to define a
      progressive and generalized loss of muscle mass and muscle strength with
      advancing age. Above certain thresholds, that loss of muscle mass and muscle
      strength is considered abnormal. Despite the progress of scientific knowledge, a
      universally accepted definition of sarcopenia is still lacking to date.
      Therefore, it is a real challenge to establish the prevalence of sarcopenia
      because the results highly depend on the definition used for its diagnosis. This
      geriatric syndrome represents a public health issue with multiple clinical
      consequences. Loss of autonomy and quality of life, altered functional status,
      increase of fatigue, falls and a higher mortality rate are well-known
      consequences of sarcopenia. Although many pharmacological and non-pharmacological
      therapeutical strategies seem to have a positive impact on muscle strength and
      muscle mass, very few studies have yet assessed the effects of those treatments
      on sarcopenia itself. Therefore, developing high-quality interventional studies,
      in this field, seem necessary.

PMID- 25065229
TI  - [Falls in the elderly].
AB  - Falls are frequent in the elderly; they can have severe consequences, and
      sometimes reveal some underlying pathology. They represent a real public health
      problem which prompts numerous teams to search for adequate preventative
      measures, adapted therapeutic options, and means to reduce the various resulting
      costs. This paper describes the multidisciplinary hospital day service organized,
      by the CHU of Liege, for older patients who fall, or are at risk of falling.

PMID- 25065230
TI  - [The effect of normal and pathological aging on cognition].
AB  - Cognitive deficits in the executive and memory domains are observed in normal
      aging and Alzheimer's disease (AD). These deficits are associated with changes at
      the brain activity level. However, a series of factors are prone to delay the
      occurrence of cognitive deficits, such as mental stimulation or physical
      activity. Similarly, cognitive rehabilitation allows improving the daily life
      functioning of patients with AD. The identification of factors and techniques
      that contribute to maintain cognitive efficiency and/or counteract the effects of
      AD will allow optimizing quality of life of older people.

PMID- 25065231
TI  - [Oxidative stress, antioxydants and the ageing process].
AB  - Antioxidant supplementation in the form of pills is thought to slow down the
      aging process through the "free radical" scavenger activity of these compounds.
      The idea arose from the "Free Radical Theory of Ageing" (FRTA), initially
      developed by Harman in 1956. In the present paper, we present some arguments
      against this theory. One of the most pertinent is that "free radicals", more
      properly renamed as reactive oxygen species (ROS), play important biological
      roles in defense mechanisms of the organism as illustrated, in particular, by the
      hormesis phenomenon. Surprisingly, a moderate production of ROS has been shown to
      extend the life span in animals.

PMID- 25065232
TI  - [Aging and cancer: coincidence or etiologic relationship?].
AB  - In Belgium and in other countries, the Cancer Registry data show an increased
      incidence of cancers related to age, the majority of tumors being diagnosed
      beyond 60 years. However, the mechanisms responsible for this increase are not
      clear. Cancer could be chronologically associated with aging because of the long
      latency period between the exposition to carcinogenic agents and the appearance
      of clinical signs. Aging could also predispose directly to cancer by different
      mechanisms (impaired immune response, increased oxidative stress, shortening of
      telomeres, accumulation of senescent cells). In this review, we propose to
      describe different hypotheses which could explain the increased incidence of
      cancers in the elderly.

PMID- 25065233
TI  - [Pharmacotherapy in the elderly: primum non nocere!].
AB  - Elderly patients, having various chronic diseases, are generally exposed to
      polypharmacy that may lead to potential adverse events. The latter may be
      explained by pharmacokinetic and pharmacodynamic particularities that render
      elderly individuals more vulnerable when exposed to certain medications.
      Recruitment of elderly patients in clinical trials is often limited, so that it
      is not always easy to determine the real benefit/risk ratio of pharmacotherapy in
      this population. Obviously, iatrogenicity is quite frequent. Therefore, in front
      of unexplained alterations of health status in an elderly individual, the
      physician should consider the possibility of a drug adverse effect. Because of
      this situation, the physician should envisage a reasonable drug prescription in
      an elderly patient. Especially, not only the initiation of drug therapy should be
      carefully analyzed, but also the opportunity to eventually stop a medication that
      may be useless or even dangerous. Rather polypharmacy per se, it is the
      inappropriate prescription that should be avoided in the elderly.

PMID- 25065234
TI  - [How to manage chronic kidney disease in the elderly?].
AB  - From age 30 onwards, kidney function physiologically decreases although this
      deterioration cannot yet be called chronic kidney disease. The latter appears in
      those exposed to cardiovascular risk factors associated with inflammation and
      oxidative stress. A diffuse atherosclerosis then develops Patients with a
      decreased glomerular filtration rate, especially below the threshold of 45
      ml/min, are characterised by a poor physical heath and by cognitive disorders,
      leading to frailty. In these conditions, a management strategy to reduce the
      increased risk of acute kidney injury should be outlined and the need for renal
      replacement therapy be considered. One must try to maintain the best possible
      quality of life, promoting in some situations a conservative approach.

PMID- 25065235
TI  - [Management of arterial hypertension in the elderly].
AB  - High blood pressure is very frequent in the elderly; it represents a real threat
      for the patient's health and a source of huge costs for the economic system.
      Systolic hypertension is the most frequent form observed in the old, due to large
      arteries stiffness. Antihypertensive therapy has proven effective to decrease
      significantly the cardiovascular morbi-mortality and total mortality in this
      population. A non pharmacological approach is also very useful, but should not be
      too restrictive. Blood pressure target in patients older than 65 (and,
      particularly, in octogenarians) is 150/80 mmHg. Blood pressure should be checked
      in the upright position before changing the drug dosage. The first line therapy
      in the old should generally be a calcium channel antagonist or a low dose
      diuretic.

PMID- 25065236
TI  - [Fibrillation, an epidemic in the elderly?].
AB  - Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical
      practice. In its non valvular form, it appears as a disorder of the aged.
      Surprisingly, its incidence and prevalence have constantly been on the rise over
      the last decades to the extent that some authors nowadays call this phenomenon an
      "emerging epidemic". The reasons for that proliferation are not entirely
      elucidated. Obesity, which has simultaneously and similarly increased in
      frequency, might have played a significant role. AF is frequently pauci
      symptomatic in the aged and can easily go unrecognized. Yet, it entails a higher
      mortality rate, carries a significant risk of thrombo-embolic events, in
      particular strokes, and may lead to heart failure. We shall briefly review the
      current epidemiologic aspects of AF and evoke the possible role of obesity. We
      shall then discuss the therapy of this disorder with a particular attention to
      the new oral anticoagulants.

PMID- 25065237
TI  - [Heart failure in the elderly].
AB  - Heart failure in the elderly represents a major public health problem.In this
      population, the general objective of therapy, defined by current guidelines, does
      not differ from that proposed for younger patients: the aims are to decrease
      symptoms, to improve quality of life, to decrease hospitalizations, and to
      increase survival. However, in this category of patients, respect for autonomy
      and quality of life remains a priority, and requires a personalized approach
      because of the geriatric characteristics of many patients.

PMID- 25065238
TI  - [Stroke and aging].
AB  - Stroke risk increases with aging and one third of ischemic strokes occurs in very
      elderly (> or = 80 years). These are responsible of two thirds of the overall
      stroke-related morbi-mortality. Stroke in very elderly differs from younger
      individuals by sex ratio (more women), risk factors (more atrial fibrillation and
      hypertension) and usually a worse functional outcome. Very elderly are likely to
      benefit from stroke unit care and early revascularisation treatments although
      they have historically been excluded from this urgent management. These issues
      are likely to worsen in the future with the increasing impact of stroke on our
      aging societies.

PMID- 25065239
TI  - [Is there still an actual place for cardiovascular prevention in the elderly?
      Focus on antiplatelet and lipid lowering agents].
AB  - The increase in life expectancy raises the difficult question of the most
      appropriate preventive medical therapy in the elderly. Indeed, beyond
      physiological age, comorbidities, contraindications and life expectancy should be
      considered before starting any treatment. Cardiovascular disease remains the
      leading cause of death in our country, especially in the elderly. A preventive
      treatment aiming at controlling cardiovascular risk factors should be initiated
      based on the currently available evidence. We shall briefly discuss the value of
      cardiovascular prevention in the elderly and specifically focus on the use (or
      not) of antiplatelet agents and lipid-lowering drugs (i.e. statins).

PMID- 25065240
TI  - [Diabetes mellitus in the elderly: from the epidemiological challenge to a
      personalized approach].
AB  - Diabetes mellitus is a common chronic disease in the elderly, being either a
      known disease with a long history (type 1 or even more often type 2 diabetes) and
      then frequently associated with various diabetic complications, or a recently
      diagnosed diabetes that may, however, have been ignored for a rather long time.
      In this latter case, diabetes may present as the occurrence or aggravation of one
      or several geriatric syndromes that overall result in a loss of autonomy. The
      global geriatric assessment, the estimation of life expectancy and the
      justification of glucose-lowering treatments should be performed at regular
      intervals in elderly diabetic people as they determine the right choice of
      glucose target levels and the best selection of glucose-lowering agents.
      Medications that can induce hypoglycaemia should ideally be avoided, especially
      in the frailty older population. The benefit-risk ratio of the proposed therapies
      should be analyzed first, and then regularly reassessed because of a potentially
      rapidly progressing condition. The recommended approach is a tailored management
      of diabetes that should integrate the clinical, functional and psycho-social
      aspects of elderly individuals.

PMID- 25065241
TI  - [Endocrine changes with aging: physiological rather than pathological].
AB  - Changes in endocrine functional status, including androgen deficiency in men,
      decreased GH and DHEA secretion (leading to loss of muscle and bone mass),
      thyroid dysfunction (especially hypothyroidism) are all much more common in older
      individuals. In this brief review we will focus on the knowledge of the
      mechanisms of each of these endocrine disorders progressing with age and analyse
      the effects of various hormonal replacement therapies on clinical outcomes in the
      elderly population. We will successively discuss the pituitary-thyroid axis
      (especially the diagnosis and treatment of hypothyroidism), the hypothalamo
      pituitary axis (deficiency in GH-IGF1), the pituitary-adrenocortical function
      (reduction in DHEA and DHEAS) and the pituitary-gonadal axis in men (late onset
      hypogonadism).

PMID- 25065242
TI  - [Constipation and fecal incontinence in the elderly].
AB  - Alterations of anorectal functions (constipation and fecal incontinence) are very
      frequent in the elderly. The patient's global evaluation with his past medical
      history, comorbidities, medications, as well as social environment and physical
      dependence, is more than ever necessary in this high risk population to guide the
      explorations and the medical care of these disorders.

PMID- 25065243
TI  - [Normal ageing of the male and female genito-urinary tract].
AB  - Normal or usual ageing of the urinary tract leads to genito-urinary dysfunctions
      without evident urogynaecological anomalies. It requires the physicians'
      awareness because these highly prevalent urinary disorders affect the seniors'
      quality of life. These troubles encompass incontinence of all types, which
      prevails in both sexes. Age, institutionalization of the individual and cognitive
      decline worsen the situation. Overactive bladder associated with older age has
      different consequences in men and women because of the potential occurrence of a
      lower urinary tract (LUT) obstruction due to benign prostate hyperplasia in men
      and of a decreased urethral resistance to leakage in women. Female prolapse can
      worsen the situation towards incontinence or LUT obstruction. Sexuality
      differently ages in the two sexes. Currently available modern urological approach
      can improve the seniors quality of life.

PMID- 25065244
TI  - [Swallowing disorders in elderly patients: a multidisciplinary approach].
AB  - Presbyphagia represents the physiological aging of swallowing function. It
      predisposes to difficulty in swallowing, namely dysphagia, which is of high
      incidence in the elderly population. The consequences of dysphagia are multiple
      and always a tragedy for the patient; they consist of aspiration pneumonia,
      malnutrition, dehydration, social isolation, and death. The diagnosis is
      difficult and is based on the medical history and clinical examination,
      associated with diagnostic tests. Its management is multidisciplinary, leaving
      only little room for medications or surgery.

PMID- 25065245
TI  - [Bucco-dental health in the elderly].
AB  - Whether they live at home or in institutions, the elderly generally have a poor
      bucco-dental health. The proportion of totally toothless patients is almost
      always higher than 50% and, among the others, the average number of remaining
      teeth is no more than ten. In the aged, this condition has several consequences
      on the quality of life, nutrition, cardiovascular diseases and pneumopathies.
      Maesures should be taken to improve this appaling state of affairs.

PMID- 25065246
TI  - [Recent advances in the treatment of presbyopia].
AB  - Everyone will experience presbyopia between the age of 45 and 50 years. The
      classical solution to help these patients is to offer spectacles or multifocal
      contact lenses. Recent developments in corneal or intraocular surgery may provide
      new solutions for selected patients to prevent them from always wearing glasses
      to read.

PMID- 25065247
TI  - [Place your bets, the die is cast ... the skin at the retiring age today and
      tomorrow].
AB  - Senescence of people represents a global expression of obsolescence of their
      organs, tissues, cells and constitutive molecules. Skin, similarly to any other
      organ, is ageing in particular ways. Over the past century, the time effects on
      skin have been expressed differently. Skin of any individual presently engaged in
      the Third Age looks different from that of his/her line ancestral. What is the
      expected future? The Third Age population is expanding and skin problems call for
      a variety of management procedures. Prevention of the diverse types of skin
      ageing has made tremendous progresses particularly in the field of preventive and
      corrective dermocosmetology. The future should further speed up such trends.

PMID- 25065248
TI  - [The specificities of orthopedic trauma in the geriatric patient].
AB  - Aging of the population represents an ubiquitous and ever-growing phenomenon in
      the developed countries. Geriatric traumatology is a constant-developping sub
      speciality of orthopedics and traumatology; it deals with the specific medical
      problems developed by older patients when affected by muskuloskeletal trauma. The
      optimal treatment of this pathology as well as the age threshold used to define
      the "geriatric" patient are still subjects of debate. Chronological age cannot be
      used as the sole inclusion criteria; physiological age as defined by
      comorbidities seems to be more appropriate. The aim of this article is to provide
      a general overview of the problems that the orthopedic surgeons faces when
      dealing with geriatric trauma: timing of surgery and anesthesia, technical
      aspects of surgery and fractures, complications and problems with the
      postoperative management of geriatric patients. Geriatric trauma is already today
      an important problem; it will certainly become a great challenge in coming years.
      The solution must reside in a multidisciplinary approach backed up by a solid
      infra-structure and good management decisions.

PMID- 25065249
TI  - [Management of the elderly in the emergency department: a suitable solution or a
      second best choice?].
AB  - The prolongation of life expectancy can only increase the proportion of elderly
      people in the future. The Emergency Departments being the main gateway to our
      hospitals, they will often have to admit such patients with their distinct
      characteristics. These individuals present with a more or less marked geriatric
      profile; it will be essential to determine their degree of frailty, a factor
      allowing to predict their survival and future level of autonomy. Evaluation tools
      have been developed to improve the management of these patients at important
      moments of their stay in the Emergency Department.

PMID- 25065250
TI  - [Elder abuse: practice issues for physicians].
AB  - Elder abuse is frequent (from 4 to 6% of adults aged 65 + according to WHO). It
      can take various forms: psychological, financial, violation of rights, neglect
      and physical. Due to demographic changes, it is expected that the number of cases
      will increase over coming years. Scientific data show the importance of a
      systemic analysis of elder abuse situations in order to avoid the simplistic
      thinking of the "horrible abuser" and the "poor victim". A multidisciplinary
      team, including a physician (a general practitioner, or a specialist), is
      necessary. Physicians can play a role in the prevention, detection and follow up
      of such cases. In order to detect elder abuse, active and attentive listening is
      mandatory. When a possibility exists that the older adult is abused, the
      suspicion should be documented (per example, by using the EASI tool), in order to
      implement an adequate follow-up. In the French part of Belgium, specialised
      services can be involved: Respect Seniors (www.respectseniors.be) in Wallonia and
      the SEPAM d'Infor-Homes in Brussels.

PMID- 25065251
TI  - [Suicide in the elderly].
AB  - In developed countries, suicide is a real public health problem. However, in
      contrast with a classical idea, suicide is not specific to young people. Indeed,
      late life suicide is a cause for major concern, particularly for those over 75
      years. Psychiatric disorders, and more specifically major depression, are clearly
      the most important risk factors. However, socio-environnemental factors, such as
      life events and social isolation, should not be overlooked. Physical disorders
      are also important clinical elements. Unfortunately, all these risk factors are
      not very specific to suicide and the early detection and treatment of people at
      high risk remain important challenges.

PMID- 25065252
TI  - [Ageism and its clinical consequences in oncogeriatry: a review of existing data
      and intervention leads].
AB  - Aging is a risk factor in oncology. Indeed, it is estimated that, in 2030, 70% of
      diagnosed cancers in the United States will concern subjects older than 65 years.
      Paradoxically, elderly are often excluded from clinical trials and are
      undertreated compared to younger patients. An important explanatory factor (and
      yet still not considered!) for these observations is the age stigma (in other
      words our stereotypes linked to age, and so ageism), age being actually the main
      motive for discrimination. In this perspective, our aim is to present ageism
      manifestations in oncogeriatry and their direct consequences for patients,
      interlocutors (that is to say health professionals) and interactions between
      them. Throughout this article, we will enhance our remarks by data from
      researches in "normal" aging. Before ending, we will give some intervention leads
      potentially applicable in oncogeriatry, to reduce ageism deleterious effect.

PMID- 25065253
TI  - [End of life care in the elderly].
AB  - The increase in life expectancy is associated with a good quality of life until a
      very old age. However, the unavoidable aging process eventually affects the
      autonomy of the patient and may force the individual to live in a nursing home.
      The alteration of sensorial functions and the increased number of degenerative
      diseases may finally induce a physical and psychological burden that might lead
      to resort to palliative care, end of life sedation, and in some cases,
      euthanasia.

PMID- 25065254
TI  - Managing change one day at a time.

PMID- 25065255
TI  - Becoming a first-class noticer. How to spot and prevent ethical failures in your
      organization.
AB  - We'd like to think that no smart, upstanding manager would ever overlook or turn
      a blind eye to threats or wrongdoing that ultimately imperil his or her business.
      Yet it happens all the time. We fall prey to obstacles that obscure or drown out
      important signals that things are amiss. Becoming a "first-class noticer," says
      Max H. Bazerman, a professor at Harvard Business School, requires conscious
      effort to fight ambiguity, motivated blindness, conflicts of interest, the
      slippery slope, and efforts of others to mislead us. As a manager, you can
      develop your noticing skills by acknowledging responsibility when things go wrong
      rather than blaming external forces beyond your control. Bazerman also advises
      taking an outsider's view to challenge the status quo. Given the string of
      ethical failures of corporations around the world in recent years--from BP to GM
      to JP Morgan Chase--it's clear that leaders not only need to act more responsibly
      themselves but also must develop keen noticing skills in their employees and
      across their organizations.

PMID- 25065256
TI  - Genetic architecture of inbreeding depression and the maintenance of gametophytic
      self-incompatibility.
AB  - Gametophytic self-incompatibility (GSI) is a widespread genetic system, which
      enables hermaphroditic plants to avoid self-fertilization and mating with close
      relatives. Inbreeding depression is thought to be the major force maintaining SI;
      however, inbreeding depression is a dynamical variable that depends in particular
      on the mating system. In this article we use multilocus, individual-based
      simulations to examine the coevolution of SI and inbreeding depression within
      finite populations. We focus on the conditions for the maintenance of SI when
      self-compatible (SC) mutants are introduced in the population by recurrent
      mutation, and compare simulation results with predictions from an analytical
      model treating inbreeding depression as a fixed parameter (thereby neglecting
      effects of purging within the SC subpopulation). In agreement with previous
      models, we observe that the maintenance of SI is associated with high inbreeding
      depression and is facilitated by high rates of self-pollination. Purging of
      deleterious mutations by SC mutants has little effect on the spread of those
      mutants as long as most deleterious alleles have weak fitness effects: in this
      case, the genetic architecture of inbreeding depression has little effect on the
      maintenance of SI. By contrast, purging may greatly enhance the spread of SC
      mutants when deleterious alleles have strong fitness effects. 

PMID- 25065257
TI  - Responses of tree species to heat waves and extreme heat events.
AB  - The number and intensity of heat waves has increased, and this trend is likely to
      continue throughout the 21st century. Often, heat waves are accompanied by
      drought conditions. It is projected that the global land area experiencing heat
      waves will double by 2020, and quadruple by 2040. Extreme heat events can impact
      a wide variety of tree functions. At the leaf level, photosynthesis is reduced,
      photooxidative stress increases, leaves abscise and the growth rate of remaining
      leaves decreases. In some species, stomatal conductance increases at high
      temperatures, which may be a mechanism for leaf cooling. At the whole plant
      level, heat stress can decrease growth and shift biomass allocation. When drought
      stress accompanies heat waves, the negative effects of heat stress are
      exacerbated and can lead to tree mortality. However, some species exhibit
      remarkable tolerance to thermal stress. Responses include changes that minimize
      stress on photosynthesis and reductions in dark respiration. Although there have
      been few studies to date, there is evidence of within-species genetic variation
      in thermal tolerance, which could be important to exploit in production forestry
      systems. Understanding the mechanisms of differing tree responses to extreme
      temperature events may be critically important for understanding how tree species
      will be affected by climate change. 

PMID- 25065258
TI  - Feruloyl esterase from the edible mushroom Panus giganteus: a potential dietary
      supplement.
AB  - A novel 61 kDa feruloyl esterase (FAE) was purified to homogeneity from freshly
      collected fruiting bodies of Panus giganteus. The isolation procedure involved
      chromatography on the ion exchangers DEAE-cellulose and Q-Sepharose, followed by
      size exclusion chromatography on Superdex 75, which produced a purified enzyme
      with a high specific activity (170.0 U/mg) which was 130-fold higher than that of
      crude extract. The purified FAE exhibited activity toward synthetic methyl esters
      and short-chain fatty acid nitrophenyl esters. The Km and Vmax for this enzyme on
      methyl ferulate were 0.36 mM and 18.97 U/mg proteins, respectively. FAE activity
      was attained at a maximum at pH 4 and 40  degrees C, respectively. The FAE
      activity was inhibited by metal ions to various degrees. The purified FAE could
      bring about the release of ferulic acid from wheat bran and corn bran under the
      action of the single purified FAE, and the amount released from wheat bran rose
      to 51.9% (of the total amount) by the synergistic action of xylanase. 

PMID- 25065259
TI  - Krishna Kumar, MD, neuromodulation and immortality.

PMID- 25065260
TI  - Neurotech report.

PMID- 25065262
TI  - The Affordable Care Act: implementation and implications for addiction specialty
      care.
AB  - Converging in 2015 are the implementation of key pieces of the Affordable Care
      Act (ACA) and the implementation of the International Classification of Diseases,
      10th edition (ICD-10). The implications for addiction care in the United States
      are substantial. This editorial discusses opportunities and challenges presented
      by these major changes to medicine and addiction specialty care.

PMID- 25065263
TI  - Markers of oxidative stress in senescent erythrocytes obtained from young and old
      age rats.
AB  - The role of oxidative stress during aging is well documented. Evidence is
      available linking animal life span to the development of oxidative stress. Up to
      a certain limit of oxidative stress, cells function to counteract the oxidant
      effects and to restore redox balance by resetting critical homeostatic
      parameters. Red blood cells (RBCs) offer a very good model to study cellular
      senescence. In vivo aging of red blood cells is associated with increased
      cellular density, which corresponds to increased cell age. The present study aims
      to investigate age-dependent oxidative stress in RBC subpopulations obtained
      after Percoll density gradient centrifugation from young and old rats. We observe
      an increase in plasma membrane redox system (PMRS) activity (p<0.001) and lipid
      peroxidation (p<0.001) between less dense and senescent RBCs in both young and
      old rats. Our findings provide evidence of a higher level of oxidative stress in
      senescent erythrocytes, with the effect being more pronounced in old (24-month
      old) rats compared to young (4-month-old) rats. The present findings emphasize
      the role of oxidative stress not only in organismal aging but also in cell
      senescence.

PMID- 25065264
TI  - Activation of TLR9-dependent p38MAPK pathway in the pathogenesis of primary
      Sjogren's syndrome in NOD/Ltj mouse.
AB  - OBJECTIVE: The objective of this study was to investigate the potential role of
      Toll-like receptor 9-dependent p38 MAPK signaling pathway in the pathogenesis of
      primary Sjogren's syndrome (pSS) in NOD/Ltj mouse, aiming to identify an ideal
      target therapy model for human pSS. METHODS: NOD/Ltj mice were chosen as a model
      of pSS. The Toll-like receptor 9 and p-p38 MAPK double-positive peripheral blood
      mononuclear cells (PBMCs) of 4-, 5-, 8-, 10-, and 15-week-old NOD/Ltj mouse were
      analyzed by flow cytometry. The expressions of Toll-like receptor 9 and p-p38
      MAPK in the submandibular gland (SMG) were also examined by immunohistochemistry.
      The change of stimulated salivary flow rate was dynamically measured, and the
      histopathology of SMG was evaluated by hematoxylin and eosin stain. RESULTS: The
      stimulated salivary flow rate in NOD/Ltj was reduced to 50-60% of the flow rate
      of control mice since the fifth week onwards. The Toll-like receptor 9 and p-p38
      MAPK double-positive PBMCs in both groups increased gradually from 5 weeks,
      peaked at 8 weeks and then gradually decreased at 10 weeks, yet the percentage of
      Toll-like receptor 9 and p-p38MAPK double-positive PBMCs in 5-, 8-, and 10-week
      old NOD/Ltj mouse was significantly increased compared with those in control
      subjects. After the 10th week onwards, there were no significant differences in
      the Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs between NOD/Ltj
      mice and controls. Immunohistochemical staining showed that Toll-like receptor 9
      was positive in the acinar epithelium cells and infiltrating lymphocytes in
      NOD/Ltj mice. p-p38 MAPK was detected in infiltrating lymphocytes and few ductal
      or acinar epithelium cells adjacent to infiltrating lymphocytes in NOD/Ltj mice.
      CONCLUSIONS: From the fifth week till the tenth week, Toll-like receptor 9 and p
      p38 MAPK double-positive PBMCs were significantly increased in NOD/Ltj mice,
      accompanied with reduced stimulated salivary flow rate and Toll-like receptor 9
      or p-p38 MAPK positive infiltrating lymphocytes observed in the SMG of NOD/Ltj
      mouse. Our results indicated that activation of Toll-like receptor 9-depended p38
      MAPK signal pathway in PBMCs was an early event in pSS which made NOD/Ltj as an
      ideal therapy model to test the treatment effects of p38 MAPK or Toll-like
      receptor 9 inhibitors on pSS.

PMID- 25065265
TI  - Mentha piperita essential oil induces apoptosis in yeast associated with both
      cytosolic and mitochondrial ROS-mediated damage.
AB  - Mentha piperita (MP), also known as peppermint, is an aromatic and medicinal
      plant widely used in the food industry, perfumery and cosmetic, pharmacy and
      traditional medicine. Its essential oil (EO) displays antimicrobial activity
      against a range of bacteria and fungi. In this study, we found that MP EO lethal
      cytotoxicity is associated with increased levels of intracellular reactive oxygen
      species, mitochondrial fragmentation and chromatin condensation, without loss of
      the plasma membrane integrity, indicative of an apoptotic process. Overexpression
      of cytosolic catalase and superoxide dismutases reverted the lethal effects of
      the EO and of its major component menthol. Conversely, deficiency in Sod1p
      (cytosolic copper-zinc-superoxide dismutase) greatly increased sensitivity to
      both agents, but deficiency in Sod2p (mitochondrial manganese superoxide
      dismutase) only induced sensitivity under respiratory growth conditions. Mentha
      piperita EO increased the frequency of respiratory deficient mutants indicative
      of damage to the mitochondrial genome, although increase in mitochondrial thiol
      oxidation does not seem to be involved in the EO toxicity. 

PMID- 25065266
TI  - Liposome-encapsulated hemoglobin enhances chemotherapy to suppress metastasis in
      mice.
AB  - Liposome-encapsulated hemoglobin with high O2 -affinity (P50 O2  = 10 mm Hg, h
      LEH) was reported to enhance tumor radiosensitivity. We hypothesize that targeted
      O2 delivery to tumor hypoxia by h-LEH may also enhance chemotherapy to suppress
      tumor growth and metastasis in mice. Doxorubicin (DXR; 0.5 or 2 mg/kg i.p.) or S
      1 (4 or 8 mg/kg orally) alone or in combination with h-LEH (5 mL/kg i.v.) was
      administered for 2 weeks to C57BL/6N mice inoculated with Lewis Lung Carcinoma
      (LLC) in the leg. After the 2-week therapy in six treatment groups, mice were
      sacrificed for quantitative assessment of tumor growth and lung metastasis. The
      tumor was then evaluated for its expression of hypoxia-inducible factor-1alpha
      (HIF-1alpha) and matrix metallopoteinase-2 (MMP-2) activity. Combined use of h
      LEH and chemotherapeutic agents (DXR or S-1) showed no additional enhancement on
      suppression of the tumor growth over the chemotherapeutic agent alone. However,
      the combination use of h-LEH significantly suppressed the number and total area
      of metastatic colonies in the lung compared with each chemotherapeutic agent
      alone. Although HIF-1alpha expression and MMP-2 activity in the original tumor
      was significantly suppressed in the groups of mice treated with either DXR or S-1
      alone, the addition of h-LEH to either agent showed further enhancement of oxygen
      mediated degradation of HIF-1alpha and suppression of MMP-2 activity. Although
      the addition of h-LEH to DXR or S-1 had little effect on original LLC tumor
      growth, it significantly enhanced suppression of lung metastasis in mice. 

PMID- 25065267
TI  - gamma-Alumina modification with long chain carboxylic acid surface nanocrystals
      for biocompatible polysulfone nanocomposites.
AB  - High performance polysulfone/gamma-alumina biocompatible nanocomposites are
      reported for the first time and the effects of gamma-alumina surface modification
      are explored. We show that some fatty acids chemisorb over the surface of gamma
      alumina forming nanosized self-assembled structures. These structures present
      thermal transitions at high temperatures, 100  degrees C higher than the melting
      temperatures of the pure acids, and are further shifted about 50  degrees C in
      the presence of polysulfone. The chemistry involved in the chemisorption is mild
      and green meeting the stringent bio sanitary protocols for biocompatible devices.
      It has been found that the self-assembled structures increase mechanical strength
      by about 20% despite the foreseeable lack of strong particle-matrix interactions,
      which manifests as small variations in both the glass transition temperature and
      the Young's modulus. Electron microscopy observation of fractured surfaces has
      revealed that some acids induce an extended region of influence around the
      nanoparticles and this fact has been used to explain the enhancement of
      mechanical strength. 

PMID- 25065268
TI  - Do premorbid and post-onset cognitive functioning differ between schizophrenia
      and bipolar disorder? A systematic review and meta-analysis.
AB  - BACKGROUND: Schizophrenia (SZ) is characterized by a broad global cognitive
      impairment that precedes the onset of the disease. By contrast, some studies
      suggest that premorbid deficits are absent, or even reversed, in bipolar disorder
      (BD). However, studies have shown impairments in cognitive functioning after the
      illness onset in both disorders. The aim of this study was to systematically
      review and meta-analyze those studies that compared premorbid and/or post-onset
      global cognitive function between SZ and BD. METHOD: We searched Medline
      (PubMed), EMBASE and PsycINFO for studies where information on cognitive
      functioning was collected in both SZ and BD within the same study or using the
      same methods. RESULTS: Compared to healthy comparison groups, SZ patients showed
      a significant premorbid cognitive impairment [standardized mean difference (SMD) 
      0.597, 95% confidence interval (CI) -0.707 to -0.487, p < 0.0001] and a large
      post-onset impairment (SMD -1.369, 95% CI -1.578 to -1.160, p < 0.0001). We found
      small significant deficits in premorbid intellectual function in the BD group
      when this was assessed retrospectively (-0.147, 95% CI -0.238 to -0.056, p =
      0.001) but not prospectively (-0.029, 95% CI -0.199 to + 0.142, p = 0.744), and
      moderate cognitive impairment after onset (SMD -0.623, 95% CI -0.717 to -0.529, p
      < 0.0001). CONCLUSIONS: SZ is characterized by significant deficits in premorbid
      intellectual function but the evidence regarding premorbid function in BD is
      equivocal. After illness onset, patients with both disorders seem to suffer a
      further decline in cognitive function but the magnitude of the impairment remains
      greater in SZ than in BD.

PMID- 25065269
TI  - Giardiasis in a hematopoietic stem cell transplant patient.
AB  - Giardiasis can mimic diarrhea secondary to mucosal injury from the conditioning
      therapy prior to hematopoietic stem cell transplant (HSCT), as well as from graft
      versus-host disease (GVHD). Herein, we describe the endoscopic diagnosis of
      giardiasis in a patient 2 months after HSCT for myelodysplastic syndrome. The
      patient was referred to gastroenterology service for suspected GVHD, but duodenal
      biopsy results showed Giardia lamblia. He was successfully treated with
      metronidazole with prompt resolution of all of his gastrointestinal symptoms.
      This case highlights the need to consider giardiasis in the differential
      diagnosis of diarrhea in the peri-transplant period.

PMID- 25065271
TI  - Impaired integration of disambiguating evidence in delusional schizophrenia
      patients.
AB  - BACKGROUND: It has been previously demonstrated that a cognitive bias against
      disconfirmatory evidence (BADE) is associated with delusions. However, small
      samples of delusional patients, reliance on difference scores and choice of
      comparison groups may have hampered the reliability of these results. In the
      present study we aimed to improve on this methodology with a recent version of
      the BADE task, and compare larger groups of schizophrenia patients with/without
      delusions to obsessive-compulsive disorder (OCD) patients, a population with
      persistent and possibly bizarre beliefs without psychosis. METHOD: A component
      analysis was used to identify cognitive operations underlying the BADE task, and
      how they differ across four groups of participants: (1) high-delusional
      schizophrenia, (2) low-delusional schizophrenia, (3) OCD patients and (4) non
      psychiatric controls. RESULTS: As in past studies, two components emerged and
      were labelled 'evidence integration' (the degree to which disambiguating
      information has been integrated) and 'conservatism' (reduced willingness to
      provide high plausibility ratings when justified), and only evidence integration
      differed between severely delusional patients and the other groups, reflecting
      delusional subjects giving higher ratings for disconfirmed interpretations and
      lower ratings for confirmed interpretations. CONCLUSIONS: These data support the
      finding that a reduced willingness to adjust beliefs when confronted with
      disconfirming evidence may be a cognitive underpinning of delusions specifically,
      rather than obsessive beliefs or other aspects of psychosis such as
      hallucinations, and illustrates a cognitive process that may underlie maintenance
      of delusions in the face of counter-evidence. This supports the possibility of
      the BADE operation being a useful target in cognitive-based therapies for
      delusions.

PMID- 25065270
TI  - Improvements in illness self-management and psychological distress associated
      with telemonitoring support for adults with diabetes.
AB  - OBJECTIVE: The objective of this observational open label trial was to
      characterize changes in diabetes self-management and psychological distress
      associated with a mobile health (mHealth) interactive voice response (IVR) self
      management support program. METHODS: For 3-6 months, 301 patients with diabetes
      received weekly IVR calls assessing health status and self-care and providing
      tailored pre-recorded self-management support messages. Patients could
      participate together with an informal caregiver who received suggestions on self
      management support, and patients' clinicians were notified automatically when
      patients reported significant problems. RESULTS: Patients completed 84% of weekly
      calls, providing 5682 patient-weeks of data. Thirty-nine percent participated
      with an informal caregiver. Outcome analyses adjusted for study design factors
      and sociodemographics indicated significant pre-post improvement in medication
      adherence, physical functioning, depressive symptoms, and diabetes-related
      distress (all p values <0.001). Analyses of self-management problems indicated
      that as the intervention proceeded, there were significant improvements in
      patients' IVR-reported frequency of weekly medication adherence, SMBG
      performance, checking feet, and frequency of abnormal self-monitored blood
      glucose readings (all p values <0.001). CONCLUSIONS: We conclude that the
      combined program of automated telemonitoring, clinician notification, and
      informal caregiver involvement was associated with consistent improvements in
      medication adherence, diabetes self-management behaviors, physical functioning,
      and psychological distress. A randomized controlled trial is needed to verify
      these encouraging findings.

PMID- 25065272
TI  - A melanocyte--melanoma precursor niche in sweat glands of volar skin.
AB  - Determination of the niche for early-stage cancer remains a challenging issue.
      Melanoma is an aggressive cancer of the melanocyte lineage. Early melanoma cells
      are often found in the epidermis around sweat ducts of human volar skin, and the
      skin pigmentation pattern is an early diagnostic sign of acral melanoma. However,
      the niche for melanoma precursors has not been determined yet. Here, we report
      that the secretory portion (SP) of eccrine sweat glands provide an anatomical
      niche for melanocyte-melanoma precursor cells. Using lineage-tagged H2B-GFP
      reporter mice, we found that melanoblasts that colonize sweat glands during
      development are maintained in an immature, slow-cycling state but renew
      themselves in response to genomic stress and provide their differentiating
      progeny to the epidermis. FISH analysis of human acral melanoma expanding in the
      epidermis revealed that unpigmented melanoblasts with significant cyclin D1 gene
      amplification reside deep in the SP of particular sweat gland(s). These findings
      indicate that sweat glands maintain melanocyte-melanoma precursors in an immature
      state in the niche and explain the preferential distribution of early melanoma
      cells around sweat glands in human volar skin. 

PMID- 25065273
TI  - Does the use of alcohol-based hand gel sanitizer reduce travellers' diarrhea and
      gastrointestinal upset?: A preliminary survey.
AB  - INTRODUCTION: Use of alcohol-based hand sanitizer is recommended by the CDC to
      reduce the risk for travellers' diarrhoea, but its effectiveness has not been
      assessed. MATERIALS AND METHODS: We investigated the potential protective effect
      of hand sanitizer use on the occurrence of diarrhoea and/or vomiting in 200
      international travellers, who were returning home, at an international airport.
      We also conducted a knowledge, aptitude and practice survey about hand gel use
      among international travellers consulting for pre-travel advice at a specialized
      clinic. RESULTS: 200 returning travellers were included of which 32.5% declared
      having used alcohol-based hand sanitizer during travel. Travellers who used hand
      sanitizer reported diarrhoea and vomiting significantly less frequently than
      those who did not (17% vs. 30%, OR = 0.47; 95% CI [0.21-0.97], p = 0.04). A total
      of 257 travellers consulting for pre-travel advice were included. A majority of
      travellers knew that hand sanitizer may be used for hand hygiene and had already
      used hand sanitizer; 72% planned to bring hand sanitizer during their next
      travel. CONCLUSIONS: Use of hand sanitizer is highly acceptable by travellers and
      is associated with a reduction in the incidence of travellers' diarrhoea and/or
      vomiting.

PMID- 25065274
TI  - Changes in oral microflora after full-mouth tooth extraction: a prospective
      cohort study.
AB  - AIM: The aim of the study was to evaluate the effect of full-mouth tooth
      extraction on the oral microflora, with emphasis on the presence and load of
      Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. MATERIAL AND
      METHODS: Adult patients (n = 30), with moderate to advanced periodontitis and
      scheduled for full-mouth tooth extraction, were consecutively selected. Prior to
      and 1 and 3 months after full-mouth tooth extraction saliva, tongue, buccal and
      gingival mucosa and subgingival plaque/prosthesis samples were obtained. Aerobic
      and anaerobic culture techniques and quantitative real-time polymerase chain
      reaction (qPCR) were employed for the detection of oral pathogens. RESULTS: Full
      mouth tooth extraction resulted in reduction below detection level of A.
      actinomycetemcomitans and P. gingivalis in 15 of 16 and 8 of 16 previously
      positive patients using culture techniques and qPCR, respectively. Those patients
      remaining qPCR positive showed a significant reduction in load of these bacteria.
      CONCLUSION: Full-mouth tooth extraction significantly changes the oral
      microflora. These changes include reduction of A. actinomycetemcomitans and P.
      gingivalis, frequently to levels below detection threshold. In some patients, A.
      actinomycetemcomitans and P. gingivalis can persist in the edentulous oral cavity
      up to 3 months after full-mouth tooth extraction.

PMID- 25065275
TI  - Acute adult and adolescent poisoning in Tehran, Iran; the epidemiologic trend
      between 2006 and 2011.
AB  - BACKGROUND: The aim of this study was to determine the frequency of each
      poisoning and its related death in our center as a sample of Tehran in six
      consecutive years (2006 to 2011). METHODS: All poisoned children and adults
      referring to Loghman-Hakim hospital poison center and hospitalized in the study
      period were enrolled and evaluated. RESULTS: In 108,265 patients, the most common
      causes of poisoning were anti-epileptics and sedative-hypnotics (22.3%). The most
      common causes of death were pesticides (24.84%) and narcotics (24.75%). In drugs
      of abuse, opium was more prevalent in the early period of the study but was
      replaced by methadone later. CONCLUSION: It seems that national policies for drug
      control and prevention of suicide have not been efficient enough. We expect to
      see Iran in the first 50 countries with regard to suicide and to maintain the
      first place in narcotic abuse if enough attention is not provided.

PMID- 25065276
TI  - Determinants of weight change in a longitudinal study of Iranian adults: Isfahan
      Cohort Study.
AB  - BACKGROUND: The extensive rise in the prevalence of obesity is a matter of great
      concern and poses a global threat to people's health. Obesity and overweight are
      considered to be the consequence of a collection of conditions including genetic,
      social, environmental, behavioral, and physical factors. The aim of this study
      was to investigate the determinants of weight change over seven years in a
      prospective study in an Iranian population. METHODS: The Isfahan Cohort Study
      (ICS) is an ongoing longitudinal study started in 2001. A total of 6504 adults
      aged >= 35 years participated in this study. Subjects were followed every 2 years
      by phone calls. The interview and measurements were repeated in 2007 for 3284
      subjects with the same protocol as the baseline study. Obesity indices, including
      body mass index (BMI) and waist circumference (WC) were measured at both time
      points. For the purpose of data analysis, multiple multinomial logistic
      regression, Chi-square, and ANOVA tests were used. RESULTS: In males, weight gain
      was more frequent from normal to overweight (11.7%), while in females, weight
      gain was observed more from overweight to obesity (11.4%). Younger individuals
      gained weight more than older individuals (P < 0.001); it was the same for lower
      education level (P = 0.007).  Weight gain was negatively (OR: 0.98, 95% CI: 0.97
      0.99 in male and OR: 0.96, 95% CI: 0.95-0.98 in female) and weight loss was
      positively (OR: 1.03, 95% CI: 1.01-1.05 in male and OR: 1.02, 95% CI: 1.01-1.04
      in female) associated with age in both sexes. Education more than 12 years in
      women and between 6-12 years in men was negatively associated with weight gain
      while smoking was positively related to weight loss in females and weight gain in
      males. CONCLUSION: Our data showed that multiple factors affect weight change,
      among which age, smoking, and education are important determinants in Iranian
      adults.

PMID- 25065277
TI  - The association between premature coronary artery disease and level of
      testosterone in young adult males.
AB  - OBJECTIVE: Low testosterone levels in men have been associated with an increased
      risk of cardiovascular disease. We aimed to identify the association between
      serum testosterone level and premature coronary artery disease (CAD) and its
      predictors in young adult males. METHODS: In this cross sectional study,
      consecutive male candidates for coronary angiography with unstable angina, no
      previous CAD and age <= 45 years were included. Serum levels of free (FT) and
      total testosterone (TT) as well as demographic and cardiovascular characteristics
      were compared between the CAD-positive and normal coronary subjects. The cutoff
      point for low TT was 2.5 ng/L. Additionally, the relationships between all the
      variables and the number of affected vessels and FT and TT and predictors of CAD
      were assessed. RESULTS: In this study, 191 patients with premature CAD were
      compared with 94 normal coronary subjects. Patients in the CAD group were
      significantly older (41.59 +/- 3.79 versus 39.27 +/- 4.97 years; P-value < 0.01),
      and had higher rates of diabetes mellitus (P-value = 0.04) and dyslipidemia (P
      value = 0.01). Serum levels of FT and TT were significantly lower in the CAD
      group than the normal coronary subjects (P-value < 0.01 for both). The rate of
      subjects with low TT increased by the number of the affected vessels (p-value for
      trend <0.01) and there was a significant correlation between the Gensini score
      and FT and TT (r = -0.37, P-value < 0.01 and r = -0.34, P-value < 0.01,
      respectively). After adjustment for confounders, the association between low TT
      and CAD remained significant (Odds ratio = 4.30, 95% confidence interval: 1.99
      9.32; P-value <= 0.001) CONCLUSION: Low levels of testosterone were associated
      with premature CAD and its severity in young adults.

PMID- 25065278
TI  - Radial artery, saphenous vein versus left internal thoracic artery in recurrent
      ischemic symptoms after coronary artery bypass graft surgery.
AB  - BACKGROUND: The long-term results of coronary artery bypass surgery depend mostly
      on the type of the grafts. For a long time, it has been accepted that arterial
      grafts are superior to venous grafts. In this study, we evaluated the
      angiographic patency rates of arterial and venous grafts. METHODS: The study took
      place between 2003 and 2013 in the Departments of Cardiovascular Surgery in
      Baskent University. The study included 52 patients with recurrent ischemic
      symptoms (of total 2183 coronary artery bypass surgery patients) following
      coronary artery bypass surgery. The patients were evaluated by control
      angiography during over mid- and long-term postoperative period (mean, 75.25 +/-
      35.15 months). Based on the angiographic findings, the grafts were divided into 3
      groups: severe stenosis, moderate stenosis, and patent. RESULTS: The preoperative
      demographics (age, gender, hypertension or diabetes mellitus) were similar in the
      three groups. The mean numbers of distal anastomoses were 3.27 +/- 0.89 (range 2
      5), the degree of native coronary artery stenosis for radial artery anastomosis
      was 79.65 +/- 17.72, and the mean numbers of radial artery and saphenous vein
      grafts were 1.19 +/- 0.44 and 1.10 +/- 0.89, respectively. The patency rate was
      80.77%for radial arteries, 63.2% for saphenous veins, and 82.4% for left internal
      thoracic arteries in the three groups. CONCLUSION: The internal thoracic artery
      graft was confirmed to be the best option for aorta-coronary bypass surgery, as
      it has the highest patency rate compared to the other grafts. Radial artery and
      saphenous vein patency rate were also seen to be similar in the long-term.

PMID- 25065279
TI  - Altered expression of alpha 2 beta 1 integrin in kidney fibroblasts: a potential
      mechanism for CsA-induced nephrotoxicity.
AB  - BACKGROUND: Nephrotoxicity is considered a significant cause of patient morbidity
      following chronic Cyclosporine A (CsA) treatment.  The exact mechanism of CsA
      induced nephrotoxicity remains to be fully clarified.  Tubulointerstitial
      fibrosis is widely regarded as a major pathway of CsA toxicity; therefore, the
      role of integrins as regulators of collagen in the extra-cellular matrix can be
      deemed pivotal. The objective of the present study was to observe the expression
      levels of alpha2beta1 integrin following CsA treatment +/- antioxidants. METHODS:
      Adhesion assay, immunofluorescent and flow cytometric analyses were performed on
      kidney fibroblasts obtained from rats after administration of CsA (25 mg/kg/day)
      +/- Vitamin E (vit. E) and Quercetin (Q) for 4 weeks.  Total RNA was collected
      from the aforementioned fibroblasts for semi-quantitative reverse transcriptase
      polymerase chain reaction analysis of alpha2 and beta1 integrins. RESULTS: We
      found that alpha2 and beta1 integrins were both markedly reduced following
      treatment with CsA, i.e., 25% and 13%, respectively, but were normal following
      subsequent consumption of the antioxidants vit. E and Q.  Attachment and
      spreading of the CsA-treated fibroblasts declined from 82% to 50%; however, this
      effect was partially reversed to 70% following antioxidant treatment. Similar
      results were observed in the spreading assay in which the level of spreading
      decreased from 73% to 21% and was subsequently restored to 46%. CONCLUSION: We
      conclude that cell adhesion, mediated by binding of integrin to collagen, which
      is a prerequisite of normal cell viability and collagen regulation, may be a
      novel pathway further explaining the nephrotoxic effects of CsA.

PMID- 25065280
TI  - Regulation of adipokines by polyunsaturated fatty acids in a rat model of non
      alcoholic steatohepatitis.
AB  - BACKGROUND: Recent evidence has indicated that polyunsaturated fatty acids
      (PUFA), such as omega-3 PUFA, have protective effects on a range of chronic
      inflammatory conditions, including obesity, and may play a role in the reversal
      of steatohepatitis. However, the effects of omega-3 PUFA on adipokine expression
      and hepatic lipid metabolism have not been well evaluated. Thus, the aim of our
      study was to investigate the effects of PUFAs on adipokines, as well as lipid and
      glycometabolism, in a rat model of non-alcoholic steatohepatitis (NASH). METHODS:
      Male Sprague-Dawley rats were divided into control, model and therapy groups. The
      control group received a normal diet, while the model and therapy groups received
      a high-fat diet. On the eighth week of high-fat diet, the therapy group was
      treated with omega-3 PUFA (1.0 g/d) daily. At the end of 20 weeks, serum
      biochemistry indices were measured and adipokine levels in serum and liver
      samples were detected with ELISA, Western blotting and real time fluorescence
      quantitative PCR (qRT-PCR). RESULTS: The weight, biochemical parameters and
      adipokine levels in serum of the model group were elevated compared to the
      control group (P < 0.05). In addition, the protein and mRNA expression levels of
      adipokines in the liver were significantly altered compared to the control group
      (P < 0.01). The therapy group was characterized by decreased weight and
      biochemical indices (P < 0.05) compared with the model group. Supplementing high
      fat diet with omega-3 PUFA decreased serum levels of leptin and resistin, while
      adiponectin levels were slightly elevated. In liver tissue samples, the protein
      and mRNA expression levels of adipokines were significantly improved (P < 0.01)
      in the therapy group compared to the model group. CONCLUSION: Omega-3 PUFA
      improved lipid and glycometabolism in NASH rats and regulated adipokine
      expression, indicating that omega-3 PUFA may have a therapeutic benefit for
      patients with NASH.

PMID- 25065281
TI  - Attenuation of phosphorylated connexin-43 protein levels in diabetic rat heart by
      regular moderate exercise.
AB  - BACKGROUND: High blood glucose levels increase the ratio of phosphorylated to non
      phosphorylated connexin-43 amounts, which leads to the decomposition of the
      hyperphosphorylated connexin-43. This can cause heart arrhythmia in diabetic
      patients. Considering the effective role of exercise in diabetic patients, and
      because there are few studies regarding the effect of exercise on phosphorylated
      connexin-43 protein levels, in the present study the impact of different periods
      of moderate regular exercise on phosphorylated Connexion-43 levels were examined.
      METHODS: Sixty (60) male Wistar rats (300 +/- 50 g) were randomly divided into
      six groups (n = 10). A week after induction of diabetes by injection of
      streptozotocin, one hour treadmill exercise, 5 days a week with 22 (m/min) speeds
      was undertaken. Left ventricles of hearts were isolated and immediately frozen.
      Finally, phosphorylated connexin-43 protein levels were measured by ELISA method.
      RESULTS: The means of blood glucose levels were significantly decreased (P <
      0/05) by increasing days of exercise. The means of blood glucose levels were
      significantly decreased (P < 0/05) by increasing days of exercise. Regular
      moderate exercise reduced the connexin-43 levels by increasing days of exercise
      (P < 0.01). CONCLUSION: It is concluded that regular moderate exercise reduces
      the amount of phosphorylated connexin-43 protein levels in the ventricular
      myocardium, by reducing blood glucose levels. This can result in partial
      inhibition of cardiac arrhythmia observed in diabetic patients. This research was
      done in Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

PMID- 25065282
TI  - A systematic review on diet quality among Iranian youth: focusing on reports from
      Tehran and Isfahan.
AB  - BACKGROUND: Lifestyle and dietary pattern in adolescence and young adulthood not
      only affect the general state of health in these years, but also leave long-term
      effects. Due to the importance of diet in youth, this systematic review
      summarized observational studies representing dietary intakes among Iranian
      adolescents and young adults. METHODS: PubMed, Scopus and Web of Science
      databases were searched up to September 2013 using keywords related to diet,
      youth and Iran. Relevant papers were identified through applying a series of
      exclusion criteria in screening steps. Data were tabulated in 4 tables according
      to the level of assessed dietary exposure including energy or nutrients, foods or
      food groups, diet quality indices or dietary patterns, and dietary habits.
      RESULTS: Out of 1348 retrieved papers, 17 papers were eligible to enter this
      systematic review. Most studies were conducted in Tehran and Isfahan. Totally,
      13113 individual were studied including 7327 girls and 5785 boys aged 10 to 28
      years. Receiving lower or higher energy than required resulted in two burdens of
      malnutrition. Fiber intake was nearly half of the recommended amounts. Among
      micronutrients, calcium, phosphorus, folate and iron had the most common
      insufficient intakes. The youth consumed low whole grain, fruits, vegetables,
      dairy and unsaturated fatty acids and low diverse diet. Skipping breakfast was
      rife. Eating fast foods and unhealthy snacks was another prevalent inappropriate
      dietary habit. CONCLUSION: Dietary intakes and habits of young people are not
      favorable. Implementing informative programs and developing practical policies
      should be noted to improve the diet quality of adolescents and young adults.

PMID- 25065283
TI  - Association between Michelin tire baby syndrome and congenital panhyopituitarism
      in an Iranian girl.
AB  - Michelin tire baby syndrome is a rare syndrome, diagnosed clinically by multiple
      circumferential skin folds. Multiple noncutaneous anomalies have been described
      with this syndrome. We report a case of Michelin tire baby syndrome with
      congenital panhypopituitarism. To date, there is no report of association between
      these two disorders. 

PMID- 25065284
TI  - Giant Virchow-Robin spaces as an incidental finding in a patient with
      parkinsonism.
AB  - Virchow-Robin spaces are perivascular spaces that surround small arteries and
      arterioles as they enter the brain parenchyma. They are usually normal findings
      on MRI of healthy people. Rarely, Virchow-Robin spaces look strikingly enlarged,
      causing mass effect and unusual cystic conformations that may be misinterpreted
      as other pathologic processes, such as a cystic neoplasm. Here, we describe a 52
      year-old woman in whom brain magnetic resonance imaging (MRI), performed to
      evaluate Parkinsonism, incidentally found giant Virchow-Robins space or Swiss
      cheese brain syndrome. In our patient, it seems that the giant Virchow-Robin
      spaces have been found incidentally and are not associated with the patient's
      Parkinsonism symptoms. 

PMID- 25065285
TI  - A case of plastic bronchitis.
AB  - Plastic bronchitis, causing airway obstruction, is a rare condition, especially
      in adults. In this paper, an adult male patient with heart failure, viral
      hepatitis, and a history of previous pneumonia, and expectorating white, plaque
      like secretions for the last 6 months is presented along with the review of the
      relevant literature. The material expectorated by the patient was evaluated;
      macroscopically, this material was observed to be identical to the shape of
      bronchial branching. Steroid treatment was commenced after the diagnosis was
      established, resulting in the nearly total disappearance of the expectorated
      material. 

PMID- 25065286
TI  - Photoclinic. Co-existence of Abernethy malformation and Klippel-Trenaunay-Weber
      syndrome.

PMID- 25065287
TI  - Setting practical conservation priorities for birds in the Western Andes of
      Colombia.
AB  - We aspired to set conservation priorities in ways that lead to direct
      conservation actions. Very large-scale strategic mapping leads to familiar
      conservation priorities exemplified by biodiversity hotspots. In contrast,
      tactical conservation actions unfold on much smaller geographical extents and
      they need to reflect the habitat loss and fragmentation that have sharply
      restricted where species now live. Our aspirations for direct, practical actions
      were demanding. First, we identified the global, strategic conservation
      priorities and then downscaled to practical local actions within the selected
      priorities. In doing this, we recognized the limitations of incomplete
      information. We started such a process in Colombia and used the results presented
      here to implement reforestation of degraded land to prevent the isolation of a
      large area of cloud forest. We used existing range maps of 171 bird species to
      identify priority conservation areas that would conserve the greatest number of
      species at risk in Colombia. By at risk species, we mean those that are endemic
      and have small ranges. The Western Andes had the highest concentrations of such
      species-100 in total-but the lowest densities of national parks. We then adjusted
      the priorities for this region by refining these species ranges by selecting only
      areas of suitable elevation and remaining habitat. The estimated ranges of these
      species shrank by 18-100% after accounting for habitat and suitable elevation.
      Setting conservation priorities on the basis of currently available range maps
      excluded priority areas in the Western Andes and, by extension, likely elsewhere
      and for other taxa. By incorporating detailed maps of remaining natural habitats,
      we made practical recommendations for conservation actions. One recommendation
      was to restore forest connections to a patch of cloud forest about to become
      isolated from the main Andes.

PMID- 25065288
TI  - Suppression of the pro-inflammatory NLRP3/interleukin-1beta pathway in
      macrophages by the thioredoxin reductase inhibitor auranofin.
AB  - BACKGROUND: The thioredoxin/thioredoxin reductase system, which is best known for
      its essential role in antioxidant defense and redox homeostasis, is increasingly
      implicated in the regulation of multiple cellular signaling pathways. In the
      present study, we asked if the thioredoxin system in macrophages might regulate
      toll-like receptor 4 (TLR4)-dependent gene expression and consequent responses.
      METHODS: Using microarray analysis we analyzed the effect of auranofin, a highly
      potent and specific inhibitor of thioredoxin reductase, on the transcriptional
      program activated in J774 macrophages by the TLR4 agonist, lipopolysaccharide
      (LPS). We used quantitative real-time PCR (qPCR), Western blotting, ELISA and
      cytotoxicity assays to confirm and extend the microarray results. RESULTS: Global
      transcriptional profiling revealed that macrophage treatment with auranofin
      exerted a selective effect on LPS-induced gene expression, suppressing the
      induction of a small number of genes. Interestingly, among these suppressed genes
      were three members of the interleukin-1 (IL-1) family of genes, among which IL
      1beta was most affected. qPCR analyses confirmed the repressive effects of
      auranofin on IL-1 genes. In addition, qPCR and Western blot analyses showed that
      auranofin impaired TLR4-dependent induction of the inflammasome receptor NLRP3,
      which plays a critical role in IL-1beta processing. Consistent with these
      findings, inflammasome-dependent release of IL-1beta from stimulated macrophages
      was suppressed by auranofin as was inflammasome-mediated cell death. CONCLUSIONS:
      Our findings suggest a regulatory role for the thioredoxin system in macrophage
      inflammatory signaling. Inhibition of the thioredoxin system in macrophages
      exerts an anti-inflammatory effect by repressing the activation of the NLRP3/IL
      1beta pathway.

PMID- 25065289
TI  - Structure, function, aging and turnover of aggrecan in the intervertebral disc.
AB  - BACKGROUND: Aggrecan is the major non-collagenous component of the intervertebral
      disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and
      the ability to form aggregates in association with hyaluronan. Its abundance and
      unique molecular features provide the disc with its osmotic properties and
      ability to withstand compressive loads. Degradation and loss of aggrecan result
      in impairment of disc function and the onset of degeneration. SCOPE OF REVIEW:
      This review summarizes current knowledge concerning the structure and function of
      aggrecan in the normal intervertebral disc and how and why these change in aging
      and degenerative disc disease. It also outlines how supplementation with aggrecan
      or a biomimetic may be of therapeutic value in treating the degenerate disc.
      MAJOR CONCLUSIONS: Aggrecan abundance reaches a plateau in the early twenties,
      declining thereafter due to proteolysis, mainly by matrix metalloproteinases and
      aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also
      participate. Aggrecan loss is an early event in disc degeneration, although it is
      a lengthy process as degradation products may accumulate in the disc for decades.
      The low turnover rate of the remaining aggrecan is an additional contributing
      factor, preventing protein renewal. It may be possible to retard the degenerative
      process by restoring the aggrecan content of the disc, or by supplementing with a
      bioimimetic possessing similar osmotic properties. GENERAL SIGNIFICANCE: This
      review provides a basis for scientists and clinicians to understand and
      appreciate the central role of aggrecan in the function, degeneration and repair
      of the intervertebral disc.

PMID- 25065290
TI  - Von Willebrand disease.

PMID- 25065291
TI  - The evolution of moment generating functions for the Wright-Fisher model of
      population genetics.
AB  - We derive and apply a partial differential equation for the moment generating
      function of the Wright-Fisher model of population genetics. 

PMID- 25065292
TI  - Long-term mortality of persons with severe mental illness and diabetes: a
      population-based cohort study in Denmark.
AB  - BACKGROUND: Persons with severe mental illness (SMI) have excess mortality, which
      may partly be explained by their high prevalence of diabetes. METHOD: We compared
      the overall and cause-specific mortality in persons with SMI and diabetes with
      that of the general Danish population between 1997 and 2009 by linking data from
      Danish national registries. RESULTS: The cohort counted 4 734 703 persons, and
      during follow-up 651 080 persons died of whom 1083 persons had SMI and diabetes.
      Compared with the background population, the overall mortality rate ratios (MRRs)
      for persons with SMI and diabetes were 4.14 [95% confidence interval (CI) 3.81
      4.51] for men and 3.13 (95% CI 2.88-3.40) for women. The cause-specific MRRs for
      persons with SMI and diabetes were lowest for malignant neoplasms (women: MRR =
      1.98, 95% CI 1.64-2.39; men: MRR = 2.08, 95% CI 1.69-2.56) and highest for
      unnatural causes of death (women: MRR = 12.31, 95% CI 6.80-22.28; men: MRR =
      7.89, 95% CI 5.51-11.29). The cumulative risks of death within 7 years of
      diabetes diagnosis for persons with SMI and diabetes were 15.0% (95% CI 12.4
      17.6%) for those younger than 50 years, 30.7% (95% CI 27.8-33.4%) for those aged
      50-69 years, and 63.8% (95% CI 58.9-68.2%) for those aged 70 years or older.
      Among persons suffering from both diseases, 33.4% of natural deaths were
      attributed to diabetes and 14% of natural deaths were attributed to the
      interaction between diabetes and SMI. CONCLUSIONS: Long-term mortality is high
      for persons with SMI and diabetes. This calls for effective intervention from a
      coordinated and collaborating healthcare system.

PMID- 25065294
TI  - Differential risks of cancer types in people with Parkinson's disease: a national
      record-linkage study.
AB  - BACKGROUND: There is evidence that people with Parkinson's disease (PD) have a
      decreased risk of developing cancer. PD has also variably been shown to be
      associated with an increased risk of cancers like melanoma and breast. We
      investigated this relationship in a very large cohort of PD patients. METHODS: We
      constructed two cohorts of people from an all-England record-linked hospital and
      mortality dataset spanning 1999-2011. One cohort comprised people with a record
      of PD; the other comprised people without a record of PD. We 'followed up' these
      two cohorts to determine observed and expected numbers of people with subsequent
      primary cancers in each, based on person-years at risk, and calculated
      standardised rate ratios (RRs). RESULTS: In 219,194 people with PD, the RR for
      all subsequent primary malignant cancers combined was 0.92 (95% confidence
      interval (CI) 0.91-0.93). Increased RRs (p<0.05) were found for six out of the 31
      cancer types investigated, including breast, melanoma, uterus, kidney, and
      neurological malignancies. Decreased RRs were found for 11 cancer sites,
      including lung and colon cancer. CONCLUSIONS: We corroborate the findings of a
      reduced risk for the development of cancers in PD patients shown in smaller
      studies, including cancers associated and not known to be associated with
      smoking; and of an increased risk of melanoma and breast cancer. To the best of
      our knowledge, this is the first study to report an association between PD and
      elevated rates of uterine and renal cancer. Further work is warranted to
      understand the mechanisms behind these findings.

PMID- 25065295
TI  - Optimization of bone-block positioning in the Bristow-Latarjet procedure: a
      biomechanical study.
AB  - BACKGROUND: In the Bristow-Latarjet procedure, optimal positioning of the
      coracoid bone-block on the anterior aspect of the glenoid (standing or lying on
      the glenoid rim) remains debated. A biomechanical study assessed the effect of
      the position of the bone-block with its attached conjoint tendon on anterior and
      inferior stabilization of the humeral head. MATERIALS AND METHODS: The Bristow
      Latarjet procedure was performed on 8 fresh cadaveric shoulders. The bone-block
      size was systematically at 2.5*1*1 cm. Anterior translation of the humeral head
      was stress induced under 30-N traction, in maximum external rotation at 0 degrees
      and at 90 degrees  abduction: respectively, adduction and external rotation
      (ADER), and abduction and external rotation (ABER). Under radiological control,
      displacement of the center of the humeral head was compared with the glenoid
      surface at the 3, 4 and 5 o'clock (medial, antero-inferior and inferior)
      positions for the 2 bone-block positionings. RESULTS: The lying position at 4
      o'clock substantially decreased anterior and inferior displacement of the humeral
      head respectively in ADER and ABER; and in ABER it also tended to decrease
      anterior translation, but not significantly. The standing bone-block position did
      not affect translation. CONCLUSIONS: Positioning the bone-block so that it lies
      on the anterior aspect of the glenoid in the middle of the antero-inferior
      quarter of the rim at 4 o'clock can decrease anterior displacement of the humeral
      head and inferior glenohumeral translation, especially in ADER for anterior
      displacement and in ABER for inferior displacement. STUDY DESIGN: Laboratory
      study.

PMID- 25065296
TI  - Childhood trauma mediates the association between ethnic minority status and more
      severe hallucinations in psychotic disorder.
AB  - BACKGROUND: Ethnic minority status and childhood trauma are established risk
      factors for psychotic disorders. Both are found to be associated with increased
      level of positive symptoms, in particular auditory hallucinations. Our main aim
      was to investigate the experience and effect of childhood trauma in patients with
      psychosis from ethnic minorities, hypothesizing that they would report more
      childhood trauma than the majority and that this would be associated with more
      current and lifetime hallucinations. METHOD: In this cross-sectional study we
      included 454 patients with a SCID-I DSM-IV diagnosis of non-affective or
      affective psychotic disorder. Current hallucinations were measured with the
      Positive and Negative Syndrome Scale (P3; Hallucinatory Behaviour). Lifetime
      hallucinations were assessed with the SCID-I items: auditory hallucinations,
      voices commenting and two or more voices conversing. Childhood trauma was
      assessed with the Childhood Trauma Questionnaire, self-report version. RESULTS:
      Patients from ethnic minority groups (n = 69) reported significantly more
      childhood trauma, specifically physical abuse/neglect, and sexual abuse. They had
      significantly more current hallucinatory behaviour and lifetime symptoms of
      hearing two or more voices conversing. Regression analyses revealed that the
      presence of childhood trauma mediated the association between ethnic minorities
      and hallucinations. CONCLUSIONS: More childhood trauma in ethnic minorities with
      psychosis may partially explain findings of more positive symptoms, especially
      hallucinations, in this group. The association between childhood trauma and these
      first-rank symptoms may in part explain this group's higher risk of being
      diagnosed with a schizophrenia-spectrum diagnosis. The findings show the
      importance of childhood trauma in symptom development in psychosis.

PMID- 25065293
TI  - Comparison of patient reported quality of life and impact of treatment side
      effects experienced with a taxane-containing regimen and standard anthracycline
      based chemotherapy for early breast cancer: 6 year results from the UK TACT trial
      (CRUK/01/001).
AB  - BACKGROUND: The TACT trial (CRUK/01/001) compared adjuvant sequential FEC
      docetaxel (FEC-D) chemotherapy with standard anthracycline-based chemotherapy of
      similar duration in women with early breast cancer. Results at a median of 5
      years suggested no improvement in disease-free survival with FEC-D. Given
      differing toxicity profiles of the regimens, the impact on quality of life (QL)
      was explored. METHODS: Patients from 44 centres completed standardised QL
      questionnaires before chemotherapy, after cycles 4 and 8, at 9, 12, 18 and 24
      months and at 6 years follow-up. Patient diaries assessed frequency, associated
      distress and impact on daily activity of 15 treatment related side effects.
      FINDINGS: 830 patients (415 FEC-D; 415 controls) contributed assessments during 0
      24 months; 362 of whom participated again at 6 years. During chemotherapy, FEC-D
      impaired global health/QL and depression rates and significantly more QL domains
      than standard regimens. Novel diary card ratings highlighted significantly more
      distress and interference with daily activities due to FEC-D side effects
      compared with standard treatment. In both groups, most QL parameters returned to
      baseline levels by 2 years and were unchanged at 6 years. INTERPRETATION: Within
      expected negative effects of chemotherapy on wide ranging QL domains FEC-D
      patients reported greater toxicity, disruption and distress during treatment with
      no improvement in disease outcome at 5 years than patients receiving standard
      anthracycline-based chemotherapy. Findings should inform future patients of
      relative costs and benefits of adjuvant chemotherapy.

PMID- 25065298
TI  - Rapid bilateral improvement in auditory cortex activity in postlingually deafened
      adults following cochlear implantation.
AB  - OBJECTIVE: Cochlear implants (CIs) can partially restore hearing, but the
      cortical changes underlying auditory rehabilitation are not well understood.
      METHODS: This prospective longitudinal study used electroencephalography (EEG) to
      examine the temporal dynamics of changes in the auditory cortex contralateral and
      ipsilateral to the CI. Postlingually deafened CI recipients (N=11; mean: 59years)
      performed an auditory frequency discrimination task after <1week, 8weeks,
      15weeks, and 59weeks of CI use. RESULTS: The CI users revealed a remarkable
      improvement in auditory discrimination ability which was most pronounced over the
      first eight weeks of CI experience. At the same time, CI users developed N1
      auditory event-related potentials (AEP) with significantly enhanced amplitude and
      decreased latency, both in the auditory cortex contralateral and ipsilateral to
      the CI. A relationship was found between the duration of deafness and the
      ipsilateral AEP latency. CONCLUSIONS: Postlingually deafened adult CI users show
      rapid adaptation of the bilateral auditory cortex. Cortical plasticity is limited
      after long duration of auditory deprivation. SIGNIFICANCE: The finding of rapid
      and limited cortical changes in adult CI recipients may be of clinical relevance
      and can help estimate the role of plasticity for therapeutic gain.

PMID- 25065297
TI  - A common SCN5A variant is associated with PR interval and atrial fibrillation
      among African Americans.
AB  - OBJECTIVE: We examined the association of rs7626962 (S1103Y) or rs7629265, a
      variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden
      cardiac death (SCD) and atrial fibrillation (AF) among African Americans.
      BACKGROUND: The SCN5A missense variant S1103Y has been associated with SCD among
      African Americans in small case-control studies, but larger population-based
      studies are needed to validate these findings. The association of this variant
      with AF has not been fully explored. METHODS: Using genotyping data on over 7,000
      African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC],
      Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of
      Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the
      association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and
      with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD
      using a population-based case-control study of SCD Cardiac Arrest Blood Study
      (CABS). RESULTS: Meta-analyses across 5 cohorts demonstrated that rs7629265 was
      significantly associated with PR duration (beta = -4.1 milliseconds; P = 2.2*10(
      6) ), but not significantly associated with QRS or QT intervals. In meta-analyses
      of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was
      associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 * 10(-4)
      ). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC
      (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly,
      S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases;
      P = 0.29). CONCLUSION: The common SCN5A variant, rs7629265, is associated with
      increased AF risk and shorter PR interval among African Americans. In contrast to
      prior reports, we found no evidence of association of rs7629265 or rs7626962
      (S1103Y) with SCD risk in the general population.

PMID- 25065299
TI  - Lambert-Eaton myasthenic syndrome - diagnosis, pathogenesis and therapy.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) describes a rare human autoimmune
      disorder of the neuromuscular junction (NMJ). Clinically, LEMS patients suffer
      from characteristic muscle weakness that is caused by the presence of antibodies
      directed against their voltage-gated calcium channels (VGCC). These channels are
      localized in the presynaptic membrane of their motor nerve terminals. Binding of
      autoimmune antibodies to the VGCCs leads to reduced neuromuscular transmission.
      In approximately 50% of the patients, LEMS is reflected by a paraneoplastic
      manifestation and most commonly associated with a small cell lung carcinoma
      (SCLC) whose cells also express VGCCs in their plasma membrane. Better
      understanding of the pathophysiological mechanisms of LEMS has helped with the
      development of new diagnostic approaches and has led to targeted symptomatic and
      immunosuppressive therapy. For LEMS patients with an underlying malignancy, tumor
      therapy is the first choice to date. 

PMID- 25065300
TI  - Electroencephalographic features of moyamoya in adults.
AB  - OBJECTIVE: Electroencephalography is useful for evaluating transient neurological
      events in the setting of moyamoya disease. METHODS: EEG findings of adults with
      moyamoya seen at a large moyamoya referral center are summarized. Patients were
      identified by retrospective chart review. RESULTS: EEGs were ordered after
      cerebral revascularization for altered mental status, aphasia, limb shaking, or
      facial twitching. Among the study population of 103 patients having EEGs, 24% of
      adults with moyamoya had a history of clinical seizures. Ischemic or hemorrhagic
      strokes were associated with a twofold relative risk of seizures. Overall, 90% of
      EEGs were abnormal, most commonly focally (78%), or diffusely slow (68%).
      Epileptiform EEG discharges were seen in 24%. Whereas hemispheres with an
      ischemic stroke had a 19% risk of epileptiform discharges and an 8% risk of
      seizures on EEG, hemispheres with hemorrhagic stroke had a 35% risk of
      epileptiform discharges and 19% risk of seizures on EEG. Focal amplitude
      attenuation was seen in 19%, breach rhythm in 15%, rhythmic delta in 14%, and
      electrographic seizures in 12%. CONCLUSIONS: Seizures and epileptiform EEG
      changes are common in patients with moyamoya disease. SIGNIFICANCE: Transient
      events in patients with moyamoya can result from seizures as well as ischemia.

PMID- 25065301
TI  - Effect of mexiletine on transitory depression of compound motor action potential
      in recessive myotonia congenita.
AB  - OBJECTIVE: We aim to demonstrate the effect of mexiletine on the compound muscle
      action potential (CMAP) amplitude transitory depression (TD) in a cohort of
      patients with recessive myotonia congenita. METHODS: We evaluated 21 patients
      with recessive myotonia congenita referred to our institute from 1990 to 2013 and
      treated with mexiletine chlorhydrate. All patients underwent prolonged 3 Hz
      repetitive nerve stimulation (3 Hz-PLRS) before and after the beginning of
      treatment. RESULTS: We observed in all subjects a reduction of CMAP amplitude TD
      after the beginning of treatment. The mean value of the TD nadir before starting
      mexiletine treatment was -62.0% and reduced to -28.8% after the therapy was
      started (51.6% reduction, p<0.001). CONCLUSIONS: The 3 Hz-PLRS is configured as a
      neurophysiological test able to indirectly detect and quantify, through the
      measurement of TD, the clinical phenomenon of the transitory weakness that occurs
      in myotonic syndromes due to CLCN1 mutations. SIGNIFICANCE: This
      neurophysiological test might be considered a helpful tool to assess the effect
      of anti-myotonic drugs, as mexiletine, in recessive myotonia congenita.

PMID- 25065302
TI  - Prognostic value of intracranial seizure onset patterns for surgical outcome of
      the treatment of epilepsy.
AB  - OBJECTIVE: To investigate if intracranial EEG patterns at seizure onset can
      predict surgical outcome. METHODS: Ictal onset patterns from intracranial EEG
      were analysed in 373 electro-clinical seizures and subclinical seizures from 69
      patients. Seizure onset patterns were classified as: (a) Diffuse
      electrodecremental (DEE); (b) Focal fast activity (FA); (c) Simultaneous onset of
      fast activity and diffuse electrodecremental event (FA-DEE); (d) Spikes; (e)
      Spike-wave activity; (f) Sharp waves; (g) Alpha activity; (h) Delta activity.
      Presence of preceding epileptiform discharge (PED) was also studied. Engel and
      ILAE surgical outcome scales were used. RESULTS: The mean follow-up period was
      42.1 months (SD=30.1). Fast activity was the most common seizure onset pattern
      seen (33%), followed by (FA-DEE) (20%), DEE (19%), spike-wave activity (12%),
      sharp-waves (6%), alpha activity (6%), delta activity (3%) and spikes (1%).
      Preceding epileptiform discharges were present in 75% of patients. FA was
      associated with favourable outcome (p=0.0083) whereas DEE was associated with
      poor outcome (p=0.0025). A widespread PED was not associated with poor outcome
      (p=0.9559). There was no clear association between seizure onset pattern and
      specific pathology, except possibly between sharp/spike waves and mesial temporal
      sclerosis. CONCLUSIONS: FA activity is associated with favourable outcome. DEE at
      onset was associated with poor surgical outcome. Widespread/bilateral PEDs were
      not associated with poor or good outcome. SIGNIFICANCE: FA appears to be the best
      marker for the epileptogenic zone. Surgery should be contemplated with caution if
      DEE is the first ictal change. However, a widespread/bilateral PED at onset is
      common and should not discourage surgery.

PMID- 25065303
TI  - The role of betel-quid chewing in smoking cessation among workers in Taiwan.
AB  - BACKGROUND: Current smokers exhibit a higher rate of betel-quid chewing than non
      smokers. However, little is known regarding the extent to which betel-quid
      chewing may affect attempts to quit smoking and smoking cessation. The aim of the
      present study is to examine the association between betel-quid chewing and
      patterns of quitting smoking. Specifically, we explore whether betel-quid chewing
      is associated with (1) current smokers who have never attempted to quit versus
      those who have attempted to quit and have failed, those who are in the process of
      quitting, and successful cessation smokers, and (2) current smokers who have
      attempted to quit and have failed versus those who have successfully quit
      smoking. METHODS: A telephone survey of 7,215 workers was conducted and obtained
      an 88.6% response rate. In the survey, the respondents' smoking and betel-quid
      chewing statuses were recorded and a list of covariates was assessed. RESULTS:
      After controlling for the effect of the covariates, betel-quid chewing was found
      to be more highly associated with current smokers who have never attempted to
      quit, compared to current smokers who are in the process of quitting (OR = 12.72;
      95% CI = 1.05-154.26), successful cessation smokers (OR = 3.62; 95% CI = 2.32
      5.65), and smokers who have attempted to quit and have failed (OR = 1.37; 95% CI
      = 1.06-1.77), respectively. In addition, betel-quid chewing is more highly
      associated with a failure to quit smoking than with successfully quitting smoking
      (OR = 3.46; 95% CI = 2.17-5.51). CONCLUSION: The findings support four plausible
      reasons why betel-quid chewing may dissuade smokers from quitting. These reasons
      highlight additional avenues for potentially reducing the smoking population in
      workplaces, such as considering work contexts and social norms, and product sales
      in smoking-cessation campaigns.

PMID- 25065304
TI  - Effect of adrenoblockers on slow (LF) waves in rabbit heart rate.
AB  - Propranolol and atenolol were used to examine the role of the adrenergic system
      in the genesis of slow HR variations (waves) in rabbits, the animals
      characterized by pronounced sympathetic influences. The control experiments were
      performed with physiological solution and long-term records in intact rabbits.
      The harmonic (spectrum) analysis was performed with fast Fourier transform. The
      adrenoblockers produced no decrease in the power of slow waves. The study did not
      found the sympathetic genesis of slow variations in rabbit HR. 

PMID- 25065305
TI  - Phosphate-dependent glutaminase response to liver injury and hyperbaric
      oxygenation.
AB  - Activity of phosphate-dependent glutaminase was determined in hepatocytes of
      white female rats, both in healthy animals and in rats with chronic CCl4
      hepatitis on day 3 after liver resection and hyperbaric oxygenation. In healthy
      animals, activity of phosphate-dependent glutaminase was not altered after
      hepatic resection, but it was elevated in animals with chronic CCl4-hepatitis.
      Hyperbaric oxygenation inhibited activity of hepatocytic phosphate-dependent
      glutaminase in non-operated healthy rats but stimulated it after hepatic
      resection. In animals with chronic CCl4-hepatitis; hyperbaric oxygenation
      restricted the stimulating effect of hepatic resection on phosphate-dependent
      glutaminase activity. 

PMID- 25065306
TI  - Effect of local application of epidermal growth factor on innate immunity and
      cell composition of destruction focus in experimental thermal injury.
AB  - The effect of recombinant human epidermal growth factor (rhEGF) on innate
      immunity and cellular composition of the destruction focus in the third-degree
      (IIIA) burn (skin contact with an object heated to 100 degrees C; 4% body
      surface) was studied in experiments on outbred albino rats. On days 7-28 after
      burn, blood count of phagocytes and their absorbing capacity and oxygen-dependent
      metabolism increased, which correlated with the increase in serum IL-1beta level
      and neutrophil count in the destruction focus. Local application of rhEGF led to
      earlier (on day 14) normalization of the count and functional activity of blood
      phagocytes and decrease in serum IL-1beta level and accelerated neutrophil and
      lymphocyte replacement with fibroblasts in the focus of injury. 

PMID- 25065307
TI  - Age- and sex-related changes in heart rate variability under conditions of
      blockade or stimulation of peripheral adrenoceptor in outbred rats.
AB  - Changes in heart rhythm variability were studied in male and female mature and 5
      6-week-old rats under conditions of 7-day administration of beta1-adrenoreceptor
      blocker atenolol (2.5 mg/kg) and alpha1-adrenoreceptor agonist phenylephrine (0.3
      mg/kg). Atenolol administration to mature rats was followed by a slight
      deceleration of cardiac rhythm, a tendency to heart rate variability decrease in
      the HF range, and moderate increase in centralization of regulation. In 6-week
      old rats, increased variability of cardiointervals and significant increase of
      centralization of the heart rhythm regulation due to an increase in the power of
      low-frequency waves (specifically VLF) were observed. In both mature and young
      rats, changes of heart rate frequency and variability in response to atenolol
      administration were more pronounced in females. Phenylephrine administration was
      followed by a significant heart rate deceleration, increase in cardiointerval
      variability and centralization of heart rate regulation in mature rats and by a
      decrease in heart rate variability in all frequency ranges in 6-week-old rats. In
      mature rats, changes in heart rate frequency and variability produced by
      phenylephrine administration were more pronounced in males; in young rats, the
      most strained heart rhythm developed in females. 

PMID- 25065308
TI  - Development of behavioral and hormonal disorders in prenatally stressed female
      rats on the model of posttraumatic stress disorder.
AB  - The dynamics of changes in behavioral and hormonal manifestations of a
      pathological state in mature female rats born by mothers exposed to daily
      restraint stress on days 15-19 of pregnancy were studied in the experimental
      model of posttraumatic stress disorder (stress-restress paradigm). Experiments
      demonstrated increased anxiety in control and prenatally stressed female rats
      after combined stress followed by restress. This parameter remained enhanced
      until day 10 after restress in control rats and day 30 in prenatally stressed
      animals. The severity of depression increased on days 1 and 10 after restress in
      prenatally stressed female rats. Basal activity of the pituitary-adrenocortical
      axis increased only in prenatally stressed female rats under these conditions.
      This parameter increased 1 day after restress and decreased after day 30. It was
      concluded that prenatal stress could increase the predisposition to post-stress
      mental pathologies in experimental animals, which are manifested in increased
      severity and duration of behavioral and hormonal impairments. 

PMID- 25065309
TI  - Effects of antenatal hypoxia on tissue homeostasis in the myocardium of albino
      rats: early and delayed consequences.
AB  - Body weight, absolute and relative heart weight, DNA-synthetic activity of
      cardiomyocytes, and number of nucleoli in cardiomyocyte nuclei were reduced in
      newborn albino rats exposed to antennal hypoxia. All these changes developed
      against the background of oxidative stress. In mature animals, the absolute and
      relative heart weights were decreased, but the ratio of mononuclear
      cardiomyocytes in both ventricles was higher than in the control. These changes
      were accompanied by an increase in the percent of collagen fibers in the
      myocardial stroma. In the right ventricle, an increase in the cardiomyocyte
      length to width ratio and a decrease in the number of nucleoli were found. The
      observed changes can probably induce heart function disturbances under
      pathological conditions.

PMID- 25065310
TI  - Effects of Lys-Glu-Trp peptide on cell-cell interactions and vascular endothelium
      proliferation under normal conditions and during atherosclerosis.
AB  - The molecular mechanism of atherosclerosis is based on decreased expression of
      signal molecules connexin (Cx37 and Cx40), vascular endothelial growth factor
      (VEGF), and proliferative protein Ki-67, which characterize the processes of cell
      cell interactions and proliferation of vascular endotheliocytes. Lys-Glu-Trp
      peptide in doses of 4 and 40 MUg/ml promoted recovery of Cx37, Cx40, and VEGF
      expression in cultured endotheliocytes from the aorta of patients with
      atherosclerosis, which attests to vasoprotective effects of this agent. 

PMID- 25065311
TI  - Effects of antenatal hypoxia on the parameters of tissue homeostasis in the liver
      of albino rats.
AB  - We studied age-dependent dynamics of some liver parameters in albino rats after
      antenatal hypoxia. A decrease in body weight, absolute liver weight in newborn
      and mature rats, and a reduction of relative weight of the liver in mature
      animals were observed under these conditions. It was found that antenatal hypoxia
      promotes a decrease in DNA-synthetic activity of hepatocytes, intensifies free
      radical processes in the liver of newborn rats, and reduces the number of
      nucleoli in hepatocytes. In mature animals, antenatal hypoxia was followed by a
      decrease in hepatocyte sizes and area of nucleoli, an increase in the number of
      binuclear cells relative to mononuclear cells, and a decrease in the number of
      nucleoli in hepatocyte nuclei. These data can reflect impairment of tissue
      homeostasis in the liver of mammals exposed to antenatal hypoxia. 

PMID- 25065312
TI  - Depolarization of atrial epicardium near pulmonary veins orifices in hypertensive
      ISIAH rats.
AB  - The formation of early activation regions was demonstrated in the area of the
      pulmonary vein orifice in hypertensive rats. The appearance of early activation
      zones on the dorsal side of the left atrium near the pulmonary veins
      simultaneously with the sinoatrial node in rats with arterial hypertension
      indicates the possibility of ectopic foci formation in the area of pulmonary vein
      sleeves. 

PMID- 25065313
TI  - Trace effects of game biofeedback: functional MRI study.
AB  - We studied the intracerebral dynamics of developing skills for self-regulation of
      psychophysiological functions in the biofeedback game model via functional MRI.
      Multiple game plots managed by physiological characteristics leave a trace in the
      form of activity zones in the middle occipital gyrus, middle temporal gyrus,
      middle frontal gyrus, inferior parietal lobule, and declive functionally related
      to cognitive actions and operations. During the development of self-regulation
      skills, the gradual shift of the localization of areas of activity is observed
      towards sensory projection fields (e.g., thalamus, superior parietal lobule),
      which indicates distribution of the load toward the perceptual areas. 

PMID- 25065314
TI  - Effect of oxidatively modified and non-modified human serum albumin on luminol
      dependent chemiluminescence of human peripheral blood leukocytes stimulated with
      opsonized zymosan.
AB  - We studied the effects of native and oxidized human serum albumin on luminol
      dependent chemiluminescence of human peripheral blood leukocytes stimulated with
      opsonized zymosan. Human serum albumin was added simultaneously with opsonized
      zymosan at the beginning of the chemiluminescent reaction. Otherwise, leukocytes
      were incubated with human serum albumin at 37 degrees C for various periods
      before addition of opsonized zymosan. Oxidized human serum albumin was obtained
      by the method of metal-catalyzed oxidation. In control to non-modified albumin,
      oxidized albumin produced an inhibitory effect on luminol-dependent
      chemiluminescence of leukocytes. These changes were observed in experiments with
      addition of oxidized albumin at the beginning of a chemiluminescent reaction and
      after incubation of study agent with cells. 

PMID- 25065315
TI  - Noopept normalizes parameters of the incretin system in rats with experimental
      diabetes.
AB  - Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that
      antihyperglycemic activity of an original nootropic and neuroprotective drug
      Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under
      conditions of oral application than after intraperitoneal injection. These data
      provided a basis for studying the effect of Noopept on major indexes of the
      incretin system. Streptozotocin was shown to decrease the concentrations of
      incretin GLP-1 and insulin in the blood. Noopept had a normalizing effect on
      these parameters. This influence of Noopept was not related to the inhibition of
      a major enzyme metabolizing incretins (dipeptidyl peptidase IV). A reference drug
      sitagliptin also increased the contents of incretins and insulin, which was
      associated with the inhibition of dipeptidyl peptidase IV. It is known that GLP-1
      increases NGF expression in the insular system. Our results suggest that the
      increase in incretin activity contributes to the antiapoptotic effect of Noopept
      on pancreatic beta cells. The mechanism for an increase in blood GLP-1 level
      after oral application of Noopept requires further investigations. 

PMID- 25065316
TI  - Role of NF-kappaB-dependent signaling in the growth capacity of mesenchymal
      progenitor cells under the influence of basic fibroblast growth factor.
AB  - We studied the in vitro role of NF-kappaB-dependent signaling in the growth
      capacity of mesenchymal progenitor cells upon stimulation by basic fibroblast
      growth factor. Proliferative activity of progenitor cells was suppressed by
      specifi c inhibitors of this transcription factor (NF-kappaB), oridonin and
      aurothiomalate. These inhibitors had no effect on differentiation of fibroblast
      CFU.

PMID- 25065317
TI  - Suppression of sulfoconjugation reduces the protective effect of ortho
      aminoazotoluene on hepatocarcinogenesis induced by diethylnitrosamine in mice.
AB  - The effects of ortho-aminoazotoluene on carcinogenic activity of
      diethylnitrosamine were studied in CBA and ICR mice. Injection of ortho
      aminoazotoluene before and after diethylnitrosamine led to a significant
      reduction of its anticarcinogenic effect, judging from significantly lower level
      of liver tumors. Pentachlorophenol, inhibitor of sulfotransferase (catalyzing the
      terminal stage of ortho-aminoazotoluene metabolic activity), stimulated its
      carcinogenic effect on mouse liver. On the other hand, pentachlorophenol reduced
      the protective effect of ortho-aminoazotoluene on diethylnitrosamine-induced
      hepatocarcinogenesis in mice. Presumably, the carcinogenic and anticarcinogenic
      effects of ortho-aminoazotoluene were realized by its initial form or
      intermediate (non-sulfated) metabolites.

PMID- 25065318
TI  - The relationship between the pro-oxidant and antioxidant system status of
      patients with multiple myeloma and the disease stage.
AB  - Disturbances of the erythrocyte antioxidant system presented by LPO
      intensification were detected in patients with multiple myeloma. Plasma
      concentrations of MDA in these patients were close to normal due to effective
      work of the nonenzymatic antioxidant system. Activities of antioxidant enzymes in
      the plasma were reduced, while catalase activity was high, and ceruloplasmin
      content did not differ from the control, this indicating suppression of the
      enzymatic component of the antioxidant system. In erythrocytes, the level of
      reduced glutathione was low, especially at stage III of the disease. Changes in
      SOD and catalase activities were similar to those in the plasma, while activities
      of glutathione-dependent enzymes were comparable to those in normal human
      erythrocytes.

PMID- 25065319
TI  - Study of exteroceptive suppression of voluntary muscular activity in healthy
      volunteers and patients with paroxysmal neuropathic pain.
AB  - The exteroceptive suppression of voluntary electromyographic activity of the
      masseter and temporal muscles was studied in healthy volunteers and patients with
      paroxysmal neuropathic pain (trigeminal neuralgia). The latent period of the
      exteroceptive suppression was prolonged and the duration of its late fragment was
      shortened in the patients in comparison with normal subjects. A short
      exteroceptive suppression period in patients with trigeminal neuralgia reflected
      deficient activity of inhibitory interneurons of the reflector loop and excessive
      activity of the antinociceptive system of the brain stem, while prolongation of
      the latent period reflected prolongation of inhibitory interneurons activation. A
      direct correlation between the degree of changes in the exteroceptive suppression
      parameters and pain intensity, evaluated by the patients by the visual analog
      scale, was detected.

PMID- 25065320
TI  - Penetration of pegylated gold nanoparticles through rat placental barrier.
AB  - Penetration of pegylated (enveloped in polyethylene glycol) gold nanoparticles 5
      and 30 nm in diameter through the placental barrier was studied in pregnant rats
      injected intravenously with these particles in a dose of about 0.8 mg Au/kg on
      day 10 of gestation. The particles were visualized in tissues by silver nitrate
      autometallography; the total content of gold in the fetuses was evaluated by
      atomic adsorption spectroscopy. Gold nanoparticles were detected in the fetal
      liver macrophages and in the spleens; high total content of gold in the fetuses
      was demonstrated for particles of both sizes. The data suggest that gold
      nanoparticles penetrate through rat placental barrier in vivo. No morphological
      changes were detected in the liver, kidneys, spleen, and brain of fetuses. 

PMID- 25065321
TI  - Study of the surface architectonics of human erythrocytes by the method of
      scanning electron microscopy in the presence of doxycycline.
AB  - The effects of doxycycline on the morphology and function of donor erythrocytes
      were studied by scanning electron microscopy. The antibiotic in concentrations of
      7.8 * 10(-5) and 7.8 * 10(-6) mol/liter induced heterogeneous changes in the
      surface architectonics in the erythrocyte population. These data indicated
      stimulation of erythrocyte "aging" under the effect of doxycycline. 

PMID- 25065322
TI  - Local tissue reaction to implantation of biodegradable suture materials.
AB  - Morphological changes in tissues adjacent to the implant were studied 1, 2, 6,
      and 12 months after implantation of biodegradable suture materials (catgut
      thread, DemeTECH polyfilament thread, and Surgilactin monofilament thread) into
      subcutaneous fat of rats. Tissue reaction to implantation of different suture
      materials developed as usual in response to a wound process and to a foreign
      body. By the end of month 1. the stage of traumatic perifocal inflammation was
      replaced in all groups by the proliferative phase with formation of new vessels
      and connective tissue. A trend to reduction of the productive inflammation
      activity from month 1 to month 12 was noted. Complete degeneration of the
      material after 12 months with complete recovery of the histoarchitecture of the
      adjacent tissues (restitution) was detected only after implantation of DemeTECH
      polyfilament thread. 

PMID- 25065323
TI  - Morphofunctional analysis of the prostate exposed to chemical manufacture
      factors.
AB  - The structural characteristics of the prostate and the blood flow in the organ
      were studied in chemical plant workers suffering from chronic prostatitis. The
      prostate echostructure was characterized by vast zones of fibrosis and
      calcinosis, the hemodynamic ultrasonic parameters were low. Degenerative changes
      in the acinar structures and stromal fibrosis predominated in the biopsy
      specimens, these shifts were the most pronounced in the peripheral and transitory
      zones. Foci of common and small-acinar degeneration of the glands, abundant
      concrements, and significant collagenization with periglandular and perivascular
      sclerosis without or with slight inflammatory infiltration were detected. We
      hypothesize that long exposure to adverse factors of sulfuric acid manufacture
      contributed to the development of pathological changes in the prostate. 

PMID- 25065324
TI  - A method for making preparations from nondecalcified articular cartilage with
      sublying subchondral bone for multipurpose studies.
AB  - A method for making preparations from nondecalcified articular cartilage and
      subchondral bone for multipurpose studies is developed. Semithin and ultrathin
      sections of nondecalcified articular cartilage and subchondral bone prepared by
      this method are used for light and transmission electron microscopy. The method
      can also be used for studies of the qualitative and quantitative characteristics
      of the articular cartilage, scanning electron microscopy, and microanalysis of
      chemical elements in the articular cartilage and subchondral bone. 

PMID- 25065325
TI  - Optogenetic approach to the studies of synaptic transmission.
AB  - Optogenetics is a modern nanobiological approaches allowing modulation of the
      physiological status of electrostimulated cells, including the neurons. The
      optogenetic approach was used to evaluate the efficiency of synaptic transmission
      between the neurons in a mixed corticostriatal culture. Synaptic contacts between
      the cortical and striatal neurons forming in a mixed culture could be modulated
      by the opticogenetic methods. Studies of the synaptic interactions between the
      neurons were essential for understanding the disease mechanisms, and therefore,
      this method seemed to be promising for biomedical studies. 

PMID- 25065326
TI  - Effects of micro-amounts of Porphyromonas gingivalis lipopolysaccharide on rabbit
      inflammatory immune response and development of atherosclerosis.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis (Pg) lipopolysaccharide is
      associated with the immune response and atherosclerosis. This study aimed to
      evaluate the effects of micro-amounts of Pg-lipopolysaccharide on rabbit
      inflammatory immune response and the development of atherosclerosis. MATERIAL AND
      METHODS: Twenty-four New Zealand white rabbits were randomly divided into four
      groups (n = 6). Group A was fed a regular diet and normal saline. Group B was
      supplied with a high-fat diet and normal saline. Group C was treated with a
      normal diet and Pg-lipopolysaccharide. Group D was given a high-fat diet and Pg
      lipopolysaccharide. After 14 wk, the rabbits were killed to determine the changes
      in pathological indices. RESULTS: The serum lipid levels of groups B and D were
      significantly higher than that of group A (p < 0.01), and that of group C was
      higher (p < 0.05). Serum interleukin-6, monocyte chemoattractant protein-1 and
      tumor necrosis factor-alpha levels were significantly elevated by individual high
      fat diets or Pg-lipopolysaccharide stimulation (p < 0.05). Groups A and C did not
      undergo evident aortic pathological damages, while foam cells appeared in the
      other two groups. Real-time polymerase chain reaction detection showed that toll
      like receptor-2, interleukin-6, matrix metalloproteinase-9 and monocyte
      chemoattractant protein-1 were highly expressed in groups B and D (p < 0.05), and
      toll-like receptor-4, C-reactive protein and tumor necrosis factor-alpha levels
      were higher than those of group A (p < 0.05). Western blotting showed that
      transcription factor NF-kappaB p65 was expressed more highly in the three
      experimental groups than in group A (t = 9.26, p < 0.01). CONCLUSION: Micro
      amounts of Pg-lipopolysaccharide induced the high expressions of inflammatory
      factors and mediated the inflammatory response. Pg-lipopolysaccharide elevated
      the blood lipid level less significantly than the high-fat diet did, but it may
      promote atherosclerosis.

PMID- 25065327
TI  - The educational value of improvisational actors to teach communication and
      relational skills: perspectives of interprofessional learners, faculty, and
      actors.
AB  - OBJECTIVE: To assess the educational value of improvisational actors in difficult
      conversation simulations to teach communication and relational skills to
      interprofessional learners. METHODS: Surveys of 192 interprofessional health care
      professionals, and 33 teaching faculty, and semi-structured interviews of 10
      actors. Descriptive statistics, Fisher's exact test and chi-square test were used
      for quantitative analyses, and the Crabtree and Miller approach was used for
      qualitative analyses. RESULTS: 191/192 (99.5%) interprofessional learners (L),
      and 31/33 (94%) teaching faculty (F) responded to surveys. All 10/10 actors
      completed interviews. Nearly all participants found the actors realistic (98%L,
      96%F), and valuable to the learning (97%L, 100%F). Most felt that role-play with
      another clinician would not have been as valuable as learning with actors (80%L,
      97%F). There were no statistically significant differences in perceived value
      between learners who participated in the simulations (47%) versus those who
      observed (53%), or between doctors, nurses, or psychosocial professionals.
      Qualitative assessment yielded five actor value themes: Realism, Actor Feedback,
      Layperson Perspective, Depth of Emotion, and Role of Improvisation in Education.
      Actors independently identified similar themes as goals of their work.
      CONCLUSIONS: The value attributed to actors was nearly universal among
      interprofessional learners and faculty, and independent of enactment
      participation versus observation. Authenticity, feedback from actors,
      patient/family perspectives, emotion, and improvisation were key educational
      elements.

PMID- 25065329
TI  - PRC1 complex diversity: where is it taking us?
AB  - Polycomb group proteins (PcGs) are essential epigenetic regulators that play key
      roles in development, pluripotency, senescence, and cancer. Recent reports have
      found that the composition of mammalian Polycomb repressive complex 1 (PRC1) is
      far more varied than previously thought. PRC1 diversity largely depends on the
      presence of CBX proteins, dividing them into canonical and non-canonical, the
      existence of redundant subunits, and different binding affinities and/or
      regulation. However, there is no clear insight into how many functional PRC1
      complexes exist and what the biological relevance is for such diversification. In
      this review we focus on mammalian PRC1 and discuss the mechanisms by which
      canonical and non-canonical PRC1 are recruited to chromatin, their role in normal
      development and disease, and emerging evidence for PRC1 as a transcriptional
      activator. 

PMID- 25065330
TI  - Inotropic agents in advanced heart failure: repetita iuvant?

PMID- 25065328
TI  - Psychosocial predictors of attitudes toward physician empathy in clinical
      encounters among 4732 1st year medical students: a report from the CHANGES study.
AB  - OBJECTIVE: Medical school curricula intended to promote empathy varies widely.
      Even the most effective curricula leave a significant group of students
      untouched. Pre-existing student factors influence their response to learning
      experiences. We examined the individual predictors of first semester medical
      students' attitudes toward the value of physician empathy in clinical encounters.
      METHODS: First year students (n=4732) attending a stratified random sample of 49
      US medical schools completed an online questionnaire that included measures of
      dispositional characteristics, attitudes and beliefs, self-concept and well
      being. RESULTS: Discomfort with uncertainty, close-mindedness, dispositional
      empathy, elitism, medical authoritarianism, egalitarianism, self-concept and well
      being all independently predicted first year medical students' attitudes toward
      the benefit of physician empathy in clinical encounters. CONCLUSION: Students
      vary on their attitude toward the value of physician empathy when they start
      medical school. The individual factors that predict their attitudes toward
      empathy may also influence their response to curricula promoting empathic care.
      PRACTICE IMPLICATIONS: Curricula in medical school promoting empathic care may be
      more universally effective if students' preexisting attitudes are taken into
      account. Messages about the importance of physician empathy may need to be framed
      in ways that are consistent with the beliefs and prior world-views of medical
      students.

PMID- 25065331
TI  - Remote tele-medicine cardiologist support for care manager nursing of chronic
      cardiovascular disease: preliminary report.

PMID- 25065332
TI  - Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor, decreases serum
      uric acid levels in type 2 diabetic patients partly by suppressing xanthine
      oxidase activity.

PMID- 25065333
TI  - Performance of transcatheter aortic valve implantation in patients with bicuspid
      aortic valve: systematic review.

PMID- 25065334
TI  - Temporal trends in all-cause mortality of smokers versus non-smokers hospitalized
      with ST-segment elevation myocardial infarction.
AB  - BACKGROUND/OBJECTIVES: Over the past decade, the development of novel management
      strategies has resulted in improved outcomes among patients hospitalized with ST
      segment myocardial infarction (STEMI). The aim of the present study was to
      compare temporal trends in the mortality of smokers versus non-smokers admitted
      with STEMI in a real world setting between 2000 and 2010. METHODS: We evaluated
      time-dependent changes in the clinical characteristics, management strategies,
      and one year all-cause mortality of STEMI patients who were enrolled in the
      biannual Acute Coronary Syndrome Israeli Survey (ACSIS) between 2000 and 2010,
      categorized as smokers (n=2399) and non-smokers (n=3069). We divided the survey
      periods into early (2000-2004) and late (2006-2010). The primary endpoint of the
      study was the occurrence of one-year all-cause mortality. RESULTS: A total of
      4564 STEMI patients were enrolled in the study. Compared with non-smokers,
      smokers were significantly younger and displayed a significantly lower rate of
      all-cause mortality at 30 days and 1-year. Both smokers and non-smokers who were
      enrolled in the late survey period received more evidence-based therapies
      (primary PCI and guideline-based medications) (p<0.001 for all). There was a
      significant reduction in the risk of 1-year all-cause mortality only among non
      smokers (HR=0.664 CI 95% 0.52-0.85, p=0.0009), whereas smokers who were enrolled
      in more recent survey periods did not display a significant risk reduction
      (HR=1.08 CI 95% 0.77-1.51, p=0.67). CONCLUSION: Survival following STEMI among
      smokers has not improved over the past decade despite corresponding changes in
      management strategies. Future trials should focus on reducing the risk in
      smokers.

PMID- 25065335
TI  - Super-selective intracoronary injection of Rho-kinase inhibitor relieves
      refractory coronary vasospasms: a case report.

PMID- 25065336
TI  - Acute myocardial infarction in Kabuki syndrome: chance occurrence or a novel risk
      factor for premature atherosclerosis?

PMID- 25065338
TI  - Intermittent left ventricular assist device inflow tract obstruction by
      prolapsing papillary muscle detected by multi-detector computed tomography
      (MDCT).

PMID- 25065337
TI  - Left ventricular diastolic function in relation to the urinary proteome: a proof
      of-concept study in a general population.
AB  - BACKGROUND: In previous studies, we identified two urinary proteomic classifiers,
      termed HF1 and HF2, which discriminated subclinical diastolic left ventricular
      (LV) dysfunction from normal. HF1 and HF2 combine information from 85 and 671
      urinary peptides, mainly up- or down-regulated collagen fragments. We sought to
      validate these classifiers in a population study. METHODS: In 745 people randomly
      recruited from a Flemish population (49.8 years; 51.3% women), we measured early
      and late diastolic peak velocities of mitral inflow (E and A) and mitral annular
      velocities (e' and a') by conventional and tissue Doppler echocardiography, and
      the urinary proteome by capillary electrophoresis coupled with mass spectrometry.
      RESULTS: In the analyses adjusted for sex, age, body mass index, blood pressure,
      heart rate, LV mass index and intake of medications, we expressed effect sizes
      per 1-SD increment in the classifiers. HF1 was associated with 0.204 cm/s lower
      e' peak velocity (95% confidence interval, 0.057-0.351; p=0.007) and 0.145 higher
      E/e' ratio (0.023-0.268; p=0.020), while HF2 was associated with a 0.174 higher
      E/e' ratio (0.046-0.302; p=0.008). According to published definitions, 67 (9.0%)
      participants had impaired LV relaxation and 96 (12.9%) had elevated LV filling
      pressure. The odds of impaired relaxation associated with HF1 was 1.38 (1.01
      1.88; p=0.043) and that of increased LV filling pressure associated with HF2 was
      1.38 (1.00-1.90; p=0.052). CONCLUSIONS: In a general population, the urinary
      proteome correlated with diastolic LV dysfunction, proving its utility for early
      diagnosis of this condition.

PMID- 25065339
TI  - Justification of an introductory electrocardiogram teaching mnemonic by
      demonstration of its prognostic value.
AB  - OBJECTIVES: With diminishing time afforded to electrocardiography in the medical
      curriculum, we have found Sibbitt's simple mnemonic, the Diagonal Line Lead Rule,
      for a pattern recognition approach to 12-lead electrocardiogram (ECG)
      interpretation to be appreciated by students. However, it still lacks universal
      acceptance because its clinical utility has not been documented. The study
      objective was to demonstrate the clinical utility of the Diagonal Line Lead ECG
      Teaching Rule. METHODS: After excluding ECGs of high-risk patients with Wolff
      Parkinson-White syndrome and QRS durations greater than 120 ms, the initial ECGs
      of the remaining 43,798 patients were scored according to the Diagonal Line Lead
      Rule. A total of 45,497 patients from the Veterans Affairs Palo Alto Healthcare
      System were referred for a routine initial resting ECG from 1987 to 1999. We
      determined cardiovascular mortality with 8 years of follow-up. RESULTS: In
      patients with normal QRS duration, diagnostic Q-wave or T-wave inversions
      isolated to the diagonal line leads showed no increased risk of cardiovascular
      death. Q-wave or T-wave inversion in any other lead was significantly associated
      with cardiovascular death with an age-adjusted Cox hazard of 2.6 (confidence
      interval, 2.4-2.8; P < .0001) and an annual cardiovascular mortality rate of
      3.0%. Leads V4-V6, I, and aVL were especially significant predictors of
      cardiovascular death, with a Cox hazard greater than 3. CONCLUSIONS: Our analysis
      demonstrates the prognostic power and clinical utility of a simple mnemonic for
      12-lead ECG interpretation that can facilitate ECG teaching and interpretation.

PMID- 25065340
TI  - Preliminary results from a prospective study of laparoscopic aortobifemoral
      bypass using a clampless and sutureless aortic anastomotic technique.
AB  - OBJECTIVE: This prospective study describes the feasibility and safety of a new
      clampless and sutureless aortic anastomotic technique used during retroperitoneal
      laparoscopic aortobifemoral bypass in extensive aortoiliac occlusive lesions.
      This is a case series of a previously published technique, demonstrating wider
      applicability of the technique. MATERIALS AND METHODS: Twelve patients underwent
      a clampless and sutureless laparoscopic bypass for TASC D aortoiliac occlusive
      lesions using the EndoVascular REtroperitoneoScopic Technique (EVREST).
      Dissection of the retroperitoneal space and the infrarenal aorta was performed
      laparoscopically. A bifurcated graft was inserted into the retroperitoneal space.
      The main body of the graft was connected on the left side of the aorta by an
      intra- and extra-aortic covered stent-graft. An aortic clamp was used temporarily
      on four patients because of excessive bleeding when the connector was deployed.
      The femoral anastomoses were performed by classic open surgery. Initial technical
      success, complications, and bypass patency were assessed. RESULTS: Median follow
      up was 9.3 months. Median operative time was 265 minutes. Median duration of
      aorto-prosthetic connection was 60 seconds. Thirty-day postoperative mortality
      was 0%. No major postoperative complications were observed. All grafts were
      patent at the end of follow-up and there was no early or late disruption of the
      proximal assembly. CONCLUSIONS: EVREST greatly facilitates laparoscopic aortic
      surgery in occlusive disease with no need for suture or clamping of the aorta.
      This technique performed in a single center on 12 patients, seems to be feasible
      and safe. It offers the advantages of laparoscopy and those of endovascular
      surgery, especially in the challenging conditions encountered during aortic
      laparoscopic surgery. Early experience supports procedural and initial
      postprocedural safety and demonstrates proof-of-concept for EVREST.

PMID- 25065341
TI  - The concept of 'intent' within Australian coronial data: factors affecting the
      National Coronial Information System's classification of mortality attributable
      to intentional self-harm.
AB  - Within Australia all unexpected deaths are investigated by the Coroners Court;
      specifically, the coroner investigates the identity of the deceased and the cause
      and circumstances of death. This 'unexpected death' category inevitably includes
      cases of self-harm and suicide. Concerns regarding the accurate reporting of
      national suicide statistics resulted in a review of the coding process undertaken
      by the Australian Bureau of Statistics (ABS), which produces the national
      statistics, and a formal Commonwealth Government Senate Inquiry in 2009. This
      article reflects data and opinions collected prior to the Senate Inquiry or the
      adjustment of the ABS coding processes, and explores the role of the Coroner in
      determining the intent of the deceased person and the role the National Coronial
      Information System (NCIS) 1 database plays in the provision of this information.
      At the Case Notification and Case Closure stages of the coronial process,
      administrative coders abstract from the coronial file the 'intent' of the
      deceased and enter the data into relevant administrative systems (which upload to
      the NCIS). The relevant intent code in the NCIS is 'Intentional Self-Harm', which
      incorporates deliberate actions of self-harm and suicide. A mixed-method study
      was employed to investigate anecdotal reports of a problematic coronial coding
      process surrounding this category of cases. A sample of Australian coroners
      (n=16), and of the national population of NCIS coders (n=36), were surveyed using
      separate instruments, and an unobtrusive case review of sampled NCIS cases
      (n=127) reflecting nine key mechanisms-of-death, was undertaken. Each Australian
      state and territory has its own Coroners Act, none of which provides legislative
      direction regarding the determination of intent by the coroner. Neither the
      coroner-respondents nor the coders favoured a standard proforma to record
      'intent'. In order to inform their classificatory decision-making regarding the
      deceased's 'intent', the coders need to abstract extensively from the entire case
      file, scrutinising documentary materials from different investigators. They rely
      primarily on the police report at Case Notification and the coroner's finding at
      Case Completion. Coders do not generally perceive the classification of 'intent'
      to be problematic; however, despite NCIS-provided coder (technical) support
      materials, there exist inconsistent coder work practices and, sometimes, absent
      documentary evidence reflecting lack of information for ascertainment and
      interpretation by the coroner, investigators, and forensic experts on the
      'intent' of the deceased. The gap between what a coroner is legally required to
      document regarding 'intent' and what society needs to know for statistical and
      preventive purposes, seems problematic to bridge.

PMID- 25065342
TI  - Iwo Eleru's place among Late Pleistocene and Early Holocene populations of North
      and East Africa.
AB  - The Iwo Eleru site in Nigeria preserves the only terminal Pleistocene fossil from
      tropical West Africa. The peoples of this region contributed to significant
      population movements throughout the continent during the Holocene. As such,
      characterizing the phenotype of Late Pleistocene West African populations is
      critical for disentangling the evolutionary signatures of a highly complex
      African population history and structure. Previous research approached the
      calvaria's morphology from a paleoanthropological perspective, noting its mosaic
      of archaic and modern neurocranial features and distinctiveness from Pleistocene
      fossil taxa and contemporary modern human samples. In this paper, I compare Iwo
      Eleru with contemporary Late Pleistocene Africans and also consider the
      specimen's affinities with Holocene populations of the central and western
      Sahara, Nile Valley, and East Africa. Craniometric data were recorded for 22
      neurocranial dimensions and subjected to principal components analysis and
      Mahalanobis distance estimation. Multidimensional scaling of distances indicated
      that Iwo Eleru fell outside the observed range of variation of other terminal
      Pleistocene supra-equatorial African populations, confirming previous results
      that documented its divergence from Neanderthals, Upper Paleolithic Europeans,
      and modern Africans. The calvaria was also distinct from Holocene Saharan, Nile
      Valley, and East African populations, which suggests limited West African input
      into the Sahara during the African Humid Period. Results presented here bolster
      previous research that suggested Iwo Eleru's anatomy reflected either admixture
      with archaic humans or the long-term survival of populations with more archaic
      neurocranial anatomy until the end of the Pleistocene. 

PMID- 25065343
TI  - High-temperature superfluidity with indirect excitons in van der Waals
      heterostructures.
AB  - All known superfluid and superconducting states of condensed matter are enabled
      by composite bosons (atoms, molecules and Cooper pairs) made of an even number of
      fermions. Temperatures where such macroscopic quantum phenomena occur are limited
      by the lesser of the binding energy and the degeneracy temperature of the bosons.
      High-critical temperature cuprate superconductors set the present record of ~100
      K. Here we propose a design for artificially structured materials to rival this
      record. The main elements of the structure are two monolayers of a transition
      metal dichalcogenide separated by an atomically thin spacer. Electrons and holes
      generated in the system would accumulate in the opposite monolayers and form
      bosonic bound states--the indirect excitons. The resultant degenerate Bose gas of
      indirect excitons would exhibit macroscopic occupation of a quantum state and
      vanishing viscosity at high temperatures.

PMID- 25065344
TI  - Naltrexone as a diagnostic tool to distinguish between hyperandrogenemic and
      hypothalamic ovarian failure in females with congenital adrenal hyperplasia due
      to 21-hydroxylase-deficiency (CAH).
AB  - OBJECTIVE: Hypothalamic ovarian failure can be considered as a differential
      diagnosis in women suffering from CAH and amenorrhea. Naltrexone can be used as a
      tool to exclude hyperandrogenemia as a cause of amenorrhea in that condition.
      STUDY DESIGN: Five women (ages between 16 and 30 years) with congenital adrenal
      hyperplasia (CAH) due to C21- hydroxylase deficiency and primary or secondary
      amenorrhoea were treated with the opiate antagonist naltrexone at a dose of 50mg
      per day. RESULT: In all patients naltrexone induced normalization of menstrual
      cycle determined by endocrine parameters and ultrasonography. CONCLUSION: Since
      naltrexone has been shown to restore normal menstrual cycles in hypothalamic
      amenorrhea it can be inferred that the cause of amenorrhea in those patients was
      not of hyperandrogenemic but of hypothalamic origin. Naltrexone may therefore be
      used to differentiate between hyperandrogenemic and hypothalamic ovarian failure
      in patients suffering from CAH.

PMID- 25065345
TI  - Mutational approaches to improve the biophysical properties of human single
      domain antibodies.
AB  - Monoclonal antibodies are a remarkably successful class of therapeutics used to
      treat a wide range of indications. There has been growing interest in smaller
      antibody fragments such as Fabs, scFvs and domain antibodies in recent years. In
      particular, the development of human VH and VL single-domain antibody
      therapeutics, as stand-alone affinity reagents or as "warheads" for larger
      molecules, are favored over other sources of antibodies due to their perceived
      lack of immunogenicity in humans. However, unlike camelid heavy-chain antibody
      variable domains (VHHs) which almost unanimously resist aggregation and are
      highly stable, human VHs and VLs are prone to aggregation and exhibit poor
      solubility. Approaches to reduce VH and VL aggregation and increase solubility
      are therefore very active areas of research within the antibody engineering
      community. Here we extensively chronicle the various mutational approaches that
      have been applied to human VHs and VLs to improve their biophysical properties
      such as expression yield, thermal stability, reversible unfolding and aggregation
      resistance. In addition, we describe stages of the VH and VL development process
      where these mutations could best be implemented. This article is part of a
      Special Issue entitled: Recent advances in molecular engineering of antibody.

PMID- 25065346
TI  - Phylogeny of Comatulidae (Echinodermata: Crinoidea: Comatulida): a new
      classification and an assessment of morphological characters for crinoid
      taxonomy.
AB  - Comatulidae Fleming, 1828 (previously, and incorrectly, Comasteridae A.H. Clark,
      1908a), is a group of feather star crinoids currently divided into four accepted
      subfamilies, 21 genera and approximately 95 nominal species. Comatulidae is the
      most commonly-encountered and species-rich crinoid group on shallow tropical
      coral reefs, particularly in the Indo-western Pacific region (IWP). We conducted
      a molecular phylogenetic analysis of the group with concatenated data from up to
      seven genes for 43 nominal species spanning 17 genera and all subfamilies. Basal
      nodes returned low support, but maximum likelihood, maximum parsimony, and
      Bayesian analyses were largely congruent, permitting an evaluation of current
      taxonomy and analysis of morphological character transformations. Two of the four
      current subfamilies were paraphyletic, whereas 15 of the 17 included genera
      returned as monophyletic. We provide a new classification with two subfamilies,
      Comatulinae and Comatellinae n. subfamily Summers, Messing, & Rouse, the former
      containing five tribes. We revised membership of analyzed genera to make them all
      clades and erected Anneissia n. gen. Summers, Messing, & Rouse. Transformation
      analyses for morphological features generally used in feather star classification
      (e.g., ray branching patterns, articulations) and those specifically for
      Comatulidae (e.g., comb pinnule form, mouth placement) were labile with
      considerable homoplasy. These traditional characters, in combination, allow for
      generic diagnoses, but in most cases we did not recover apomorphies for
      subfamilies, tribes, and genera. New morphological characters that will be
      informative for crinoid taxonomy and identification are still needed. DNA
      sequence data currently provides the most reliable method of identification to
      the species-level for many taxa of Comatulidae. 

PMID- 25065347
TI  - Acute liver failure after valproate exposure in patients with POLG1 mutations and
      the prognosis after liver transplantation.
AB  - Patients with mutations in the POLG1 gene encoding mitochondrial DNA polymerase
      gamma have an increased risk of valproate-induced liver failure. POLG1 mutations
      are common, and these patients often suffer from intractable seizures. The role
      of liver transplantation in the treatment of patients with mitochondrial diseases
      has been controversial. We studied valproate-induced liver failure associated
      with POLG1 mutations and the prognosis for these patients after liver
      transplantation. POLG1 was analyzed in blood DNA, mitochondrial DNA (mtDNA) was
      quantified in liver samples, and clinical data were collected. Five patients with
      valproate-induced liver failure associated with POLG1 mutations were
      retrospectively identified. Three patients were previously suspected to have
      Wilson's disease. Four patients with homozygous p.W748S and p.E1143G mutations
      had mtDNA depletion in the liver. One of these patients died before anticipated
      transplantation; the other 3 patients with liver transplantation have survived 4
      to 19 years. Two patients have presented with occasional epileptic seizures, and
      1 patient has been seizure-free for 11 years. One patient with a heterozygous
      p.Q1236H mutation (but without mtDNA depletion in the liver) died suddenly 2
      years after liver transplantation. In conclusion, the POLG1 mutation status and
      the age at presentation of valproate-induced liver failure can affect the
      prognosis after liver transplantation. A heterozygous POLG1 p.Q1236H mutation was
      related to valproate-induced liver failure without mtDNA depletion, whereas
      patients homozygous for POLG1 p.W748S and p.E1143G mutations had mtDNA depletion.
      An analysis of the POLG1 gene should be performed for all patients with suspected
      mitochondrial disease before the introduction of valproate therapy, and treatment
      with valproic acid should be avoided in these patients.

PMID- 25065348
TI  - Sailing to the port of best practice on the A/I practice parameters Mayflower.

PMID- 25065349
TI  - Special challenges in treatment and self-management of older women with asthma.

PMID- 25065350
TI  - Management of acute loss of asthma control in the yellow zone: a practice
      parameter.

PMID- 25065351
TI  - A case of anaphylaxis to palivizumab.

PMID- 25065352
TI  - Allergen of the month--Little-leaf linden.

PMID- 25065353
TI  - Practices of pediatric oncology and hematology providers regarding fertility
      issues: a European survey.
AB  - BACKGROUND: Fertility is impaired in many survivors of childhood cancer following
      treatment. Preservation of fertility after cancer has become a central
      survivorship concern. Nevertheless, several doctors, patients, and families do
      not discuss fertility and recommendations for fertility preservation in
      pediatrics are still lacking. Recommendations based on scientific evidence are
      needed and before their development we wanted to assess the practice patterns of
      fertility preservation in Europe. PROCEDURES: On behalf of the PanCare network,
      we sent a questionnaire to pediatric onco-hematology institutions across Europe.
      The survey consisted of 21 questions assessing their usual practices around
      fertility preservation. RESULTS: One hundred ninety-eight institutional
      representatives across Europe received the survey and 68 (response rate 34.3%)
      responded. Pre-treatment fertility counseling was offered by 64 institutions.
      Counseling was done by a pediatric onco-hematologist in 52% (33/64) and in 32%
      (20/64) by a team. The majority of institutions (53%) lacked recommendations for
      fertility preservation. All 64 centers offered sperm banking; eight offered
      testicular tissue cryopreservation for pre-pubertal males. For females, the
      possibility of preserving ovarian tissue was offered by 40 institutions.
      CONCLUSIONS: There is a high level of interest in fertility preservation among
      European centers responding to our survey. However, while most recommended sperm
      cryopreservation, many also recommended technologies whose efficacy has not been
      shown. There is an urgent need for evidence-based European recommendations for
      fertility preservation to help survivors deal with the stressful topic of
      fertility.

PMID- 25065354
TI  - Interpretation of group-level factors from a large population dataset in the
      determination of ethyl glucuronide in hair.
AB  - Ethyl glucuronide in hair (HEtG) is the most accredited marker to prove chronic
      alcohol abuse. In this study, we evaluate the comprehensive results of HEtG
      determination obtained during four years of activity (2009-2013) in our
      laboratory (Northwestern Italy) - across a large cohort of subjects (over 20 000
      subjects mostly undergoing medical examination for driving re-licensing) - to
      provide a general perspective on HEtG analysis and dependence on group-level
      factors (e.g. age, gender, site and period of hair collection) that could bias
      the analytical results. HEtG was measured by liquid chromatography-tandem mass
      spectrometry. About 12% of the subjects presented HEtG concentrations over 30
      pg/mg. Upon non-parametric hypothesis tests, distributions of HEtG in independent
      populations categorized by age proved statistically different, while no
      differences were found by considering gender, BMI, and site of sampling (head vs.
      chest hair). A 'seasonality' factor was evaluated by comparing periods of
      collection approximately representing the hair growth in winter, spring, summer
      and autumn, and a seasonal trend was observed showing the highest HEtG levels in
      winter (16.7%) and minimum levels in summer (8.3%). The experimental HEtG
      distributions confirm that chest hair sampling can be trusted as an alternative
      to scalp. Furthermore, among biological and external factors, age and season of
      sampling may significantly influence the measured HEtG concentration, and this
      potential source of bias should be taken into account when the results are
      interpreted.

PMID- 25065355
TI  - Reactivity of an intramolecular fluorophosphonium fluoroborate.
AB  - The reactions of the intramolecular frustrated Lewis pair-adduct Ph(2) PC(p
      Tol)=C(C(6) F(5))B(C(6)F(5))2 (CNtBu) with XeF(2) gave Ph(2)P(F)C(p
      Tol)=C(C(6)F(5))B(F)(C(6)F(5))(2)(3). This species reacts with two equivalents of
      Al(C(6)F(5))(3)?C(7)H(8) producing the salt, [Ph(2)P(F)C(p
      Tol)=C(C(6)F(5))B(C(6)F(5))(2)][F(Al(C(6)F(5))(3))(2)] (4), whereas reaction with
      HSiEt(3)/B(C(6)F(5))(3) gave Ph(2) P(F)C(p-Tol)=C(H)B(C(6)F(5))(3) (5). The
      photolysis of 3 resulted in aromatization affording the phenanthralene derivative
      Ph(2) P(F)C(p-Tol(o-C(6)F(4)))=CB(F)(C(6)F(5))(2) (6).

PMID- 25065356
TI  - Origin of the anterior cruciate ligament and the surrounding osseous landmarks of
      the femur.
AB  - The aims of this study were to evaluate the discernibility of the LIR (lateral
      intercondylar ridge) and the LBR (lateral bifurcate ridge) and show their
      reliability in femoral tunnel placement in ACL (anterior cruciate ligament)
      reconstruction. Additionally, their position to the femoral axis, their course,
      and the ACL footprint were analyzed. For this study, 235 human femora were
      evaluated. Of these, 166 specimens originated from the Museum of Natural History
      (group A), and 69 were obtained from fixed cadavers at the Anatomic Institute
      (group B). The femoral footprint and the osseous landmarks were identified
      macroscopically and labeled in the photographs. A coordinate system was outlined,
      and the dimensions, position, and orientation of the femoral footprint of the ACL
      were measured. The LBR was found in 24.7% of the specimens in group A and in only
      13.2% of the specimens in group B. The LIR was found in 97.9% and 85.3% of the
      specimens in groups A and B, respectively. The area of the ACL footprint was
      127.21 +/- 32.54 mm(2) in group A and 119.58 +/- 34.84 mm(2) in group B. The
      shapes and angles of the osseous landmarks near the line of Blumensaat were
      highly variable. The LBR is an unreliable intraoperative landmark for
      arthroscopic ACL reconstruction due to its low incidence. Other anatomical
      structures, such as the LIR or the osteochondral border, may be more helpful and
      reliable landmarks to guide proper tunnel placement.

PMID- 25065357
TI  - Protease-activated receptor 2 suppresses lymphangiogenesis and subsequent lymph
      node metastasis in a murine pancreatic cancer model.
AB  - Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that
      functions as a cell-surface sensor for coagulation factors and other proteases
      associated with the tumour microenvironment. Pancreatic cancer cells express high
      levels of PAR-2 and activation of PAR-2 may induce their proliferation and
      migration. Interestingly, however, PAR-2 expression is increased in stroma-rich
      pancreatic cancer regions, suggesting a potential role of PAR-2 in the tumour
      microenvironment. Here, we assessed the importance of PAR-2 in the stromal
      compartment by utilizing an orthotopic pancreatic cancer model, in which tumour
      cells are PAR-2-positive, whereas stromal cells are PAR-2-negative. We assessed
      tumour weight and volume and analysed proliferation and (lymph)angiogenesis both
      in vivo and in vitro. We show that genetic ablation of PAR-2 from the stromal
      compartment inhibits primary tumour growth, which is accompanied by reduced
      vascularization in primary tumours and reduced in tube formation of vascular
      endothelial cells in vitro. In contrast to smaller primary tumours, the number of
      lymph node metastases was increased in PAR-2-deficient animals, which was
      accompanied by an increased number of lymphatic vessels. In vitro tube-formation
      assays show that PAR-2 does not inhibit the intrinsic tube-forming capacity of
      lymphatic endothelial cells, but that PAR-2 actually inhibits cancer cell-induced
      tube formation. Overall, stromal PAR-2 thus plays a dual role in pancreatic
      cancer development by potentiating primary tumour growth but limiting
      lymphangiogenesis and subsequent lymph node metastasis. Our data identify a novel
      role of PAR-2 in the tumour microenvironment and pinpoint PAR-2 as a negative
      regulator of lymphangiogenesis.

PMID- 25065358
TI  - Issues that face rural surgery in the United States.

PMID- 25065359
TI  - Surgical management of advanced gastrointestinal stromal tumors: an international
      multi-institutional analysis of 158 patients.
AB  - BACKGROUND: Patients with advanced gastrointestinal stromal tumors (GIST) are at
      high risk for recurrence after surgery. The aim of this study was to characterize
      outcomes of advanced GIST treated with surgery from a large multi-institutional
      database in the tyrosine kinase inhibitor (TKI) era. STUDY DESIGN: Patients who
      underwent surgery for an advanced GIST from 1998 through 2012 were identified.
      Demographic, clinicopathologic, perioperative, and survival data were collected
      and analyzed. RESULTS: There were 87 patients with locally advanced GIST and 71
      patients with recurrent/metastatic GIST. The vast majority (95%) of patients with
      locally advanced GIST required a multivisceral resection; most patients (87%)
      underwent a microscopically complete (R0) resection. Although 82% of patients had
      high-risk tumors according to modified NIH criteria or had recurrent/metastatic
      disease, only 56% of patients received adjuvant TKI therapy. Among patients with
      locally advanced GIST, 3-year recurrence-free survival and overall survival rates
      were 65% and 87%, respectively. In contrast, 3-year recurrence-free survival and
      overall survival rates among patients with recurrent/metastatic GIST were 49% and
      82%, respectively. On multivariate analysis, predictors of worse outcomes
      included high mitotic rate and male sex for patients with locally advanced GIST,
      and age and lack of adjuvant TKI therapy were associated with adverse outcomes
      among patients with recurrent/metastatic GIST (all p < 0.05). CONCLUSIONS:
      Resection of advanced GIST can be safely accomplished with high rates of R0
      resection. Among patients with advanced GIST, TKI therapy was underused. Barriers
      to the use of TKI therapy in this population should be explored.

PMID- 25065360
TI  - Disconnected pancreatic duct syndrome: disease classification and management
      strategies.
AB  - BACKGROUND: Disconnected pancreatic duct syndrome (DPDS) typically complicates
      acute necrotizing pancreatitis (ANP) and presents as a pseudocyst months after
      the initial episode of pancreatitis. However, our experience suggests that the
      presentation of DPDS may be quite varied and might require significant evaluation
      and judgment before surgical intervention. We sought to determine the
      presentations of DPDS and assess the management of the various forms of
      presentation. STUDY DESIGN: A retrospective review of all patients with DPDS
      between July 2005 and June 2011 was performed. Patients were included when CT
      scan demonstrated a clear disconnected pancreas that was confirmed at operation.
      Medical records were reviewed in detail to determine clinical presentation,
      management, and outcomes. RESULTS: Of the 50 patients identified, 66% were male,
      with a mean age of 53 +/- 16 years. Mortality was 2% and 3 patients (6%) required
      late reoperation. The DPDS presented in 3 forms: diagnosed concurrently with ANP
      (concurrent DPDS; n = 28); delayed presentation with a pseudocyst (delayed DPDS;
      n = 15); and as a consequence of chronic pancreatitis (CP) (CP DPDS; n = 7).
      Concurrent DPDS was treated with necrosectomy including body/tail resection
      within 60 days of onset and complicated by a grade B/C fistula in 36%. Delayed
      DPDS required distal pancreatectomy 440 days after diagnosis, with a 7% fistula
      rate. Chronic pancreatitis DPDS was treated with lateral pancreatojejunostomy at
      417 days with no fistulas. CONCLUSIONS: Disconnected pancreatic duct syndrome
      presents concurrently with ANP, in a delayed fashion, or infrequently in the
      setting of CP. Prompt recognition and classification with appropriate operative
      therapy results in low mortality and nonoperatively managed pancreatic fistulas.

PMID- 25065361
TI  - A 20-year experience with liver transplantation for polycystic liver disease:
      does previous palliative surgical intervention affect outcomes?
AB  - BACKGROUND: Although it is the only curative treatment for polycystic liver
      disease (PLD), orthotopic liver transplantation (OLT) has been reserved for
      severely symptomatic, malnourished, or refractory patients who are not candidates
      for palliative disease-directed interventions (DDI). Data on the effect of
      previous DDIs on post-transplant morbidity and mortality are scarce. We analyzed
      the outcomes after OLT for PLD recipients, and determined the effects of previous
      palliative surgical intervention on post-transplantation morbidity and mortality.
      STUDY DESIGN: We performed a retrospective analysis of factors affecting
      perioperative outcomes after OLT for PLD between 1992 and 2013, including
      comparisons of recipients with previous major open DDIs (Open DDI, n = 12) with
      recipients with minimally invasive or no previous DDIs (minimal DDI, n = 16).
      RESULTS: Over the 20-year period, 28 recipients underwent OLT for PLD, with
      overall 30-day, 1-, and 5-year graft and patient survivals of 96%, 89%, 75%, and
      96%, 93%, 79%, respectively. Compared with the minimal DDI group, open DDI
      recipients accounted for all 5 deaths, had inferior 90-day and 1- and 5-year
      survivals (83%, 83%, and 48% vs 100%, 100%, 100%; p = 0.009), and greater
      intraoperative (42% vs 0%; p = 0.003), total (58% vs 19%; p = 0.031), and Clavien
      grade IV or greater (50% vs 6%; p = 0.007) postoperative complications, more
      unplanned reoperations (50% vs 13%; p = 0.003), and longer total hospital (27
      days vs 17 days; p = 0.035) and ICU (10 days vs 4 days; p = 0.045) stays.
      CONCLUSIONS: In one of the largest single-institution experiences of OLT for PLD,
      we report excellent long-term graft and patient survival. Previous open DDIs are
      associated with increased risks of perioperative morbidity and mortality.
      Improved identification of PLD patients bound for OLT may mitigate perioperative
      complications and potentially improve post-transplantation outcomes.

PMID- 25065362
TI  - Cortical thickness and inattention/hyperactivity symptoms in young children: a
      population-based study.
AB  - BACKGROUND: While many neuroimaging studies have investigated the neurobiological
      basis of attention deficit hyperactivity disorder (ADHD), few have studied the
      neurobiology of attention problems in the general population. The ability to pay
      attention falls along a continuum within the population, with children with ADHD
      at one extreme of the spectrum and, therefore, a dimensional perspective of
      evaluating attention problems has an added value to the existing literature. Our
      goal was to investigate the relationship between cortical thickness and
      inattention and hyperactivity symptoms in a large population of young children.
      METHOD: This study is embedded within the Generation R Study and includes 6- to 8
      year-old children (n = 444) with parent-reported attention and hyperactivity
      measures and high-resolution structural imaging data. We investigated the
      relationship between cortical thickness across the entire brain and the Child
      Behavior Checklist Attention Deficit Hyperactivity Problems score. RESULTS: We
      found that greater attention problems and hyperactivity were associated with a
      thinner right and left postcentral gyrus. When correcting for potential
      confounding factors and multiple testing, these associations remained
      significant. CONCLUSIONS: In a large, population-based sample we showed that
      young (6- to 8-year-old) children who show more attention problems and
      hyperactivity have a thinner cortex in the region of the right and left
      postcentral gyrus. The postcentral gyrus, being the primary somatosensory cortex,
      reaches its peak growth early in development. Therefore, the thinner cortex in
      this region may reflect either a deviation in cortical maturation or a failure to
      reach the same peak cortical thickness compared with children without attention
      or hyperactivity problems.

PMID- 25065363
TI  - Urothelial dysfunction and chronic inflammation in patients with spinal cord
      injuries at different levels and correlation with urodynamic findings.
AB  - AIMS: To investigate urothelial dysfunction and suburothelial inflammation in
      patients with chronic SCI at different spinal cord levels. METHODS:
      Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase
      (mast cell activation), and apoptosis tests on bladder biopsy specimens including
      urothelium and suburothelium were performed in 34 chronic SCI patients and 10
      controls. Video-urodynamic studies were also analyzed and correlated with
      immunofluorescence findings. RESULTS: The mean interval from SCI to bladder
      biopsy was 9.3 +/- 8.4 years. Patients with chronic SCI had significantly lower
      expression of E-cadherin (20.86 +/- 14.07 vs. 42.40 +/- 16.73, the fluorescence
      intensity per 4 um(2)) and ZO-1 (5.54 +/- 3.73 vs. 11.01 +/- 5.66, the
      fluorescence intensity per 4 um(2)) than controls (both P < 0.05). Additionally,
      suburothelial activated mast cells (16.60 +/- 6.85 vs. 1.25 +/- 1.15, positive
      cells per 100 cells) and apoptotic cell numbers (5.39 +/- 4.86 vs. 0.08 +/- 0.26,
      positive cells per 100 cells) were significantly higher than in controls (both P
      < 0.05). Immunofluorescence characteristics and video-urodynamic findings did not
      differ between patients with 15 cervical and 19 thoracic SCIs. Suburothelial
      activated mast cell numbers correlated negatively to E-cadherin expression in the
      urothelium (r = -0.559, P < 0.05). Additionally, apoptotic cell number correlated
      negatively with cystometric bladder capacity (r = -0.535, P < 0.05). CONCLUSIONS:
      Decreased expression of urothelial adhesion and junction proteins and increased
      suburothelial inflammation and apoptosis were found in patients with chronic SCI,
      regardless of injury level. Such mechanisms might contribute to the vulnerability
      of patients with SCI to cystitis and recurrent bacterial infections.

PMID- 25065365
TI  - Controllable copper deficiency in Cu2-xSe nanocrystals with tunable localized
      surface plasmon resonance and enhanced chemiluminescence.
AB  - Copper chalcogenide nanocrystals (CuCNCs) as a type of semiconductor that can
      also act as efficient catalysts are rarely reported. Herein, we study water
      soluble size-controlled Cu(2-x)Se nanocrystals (NCs), which are copper deficient
      and could be prepared by a redox reaction with the assistance of surfactants. We
      found them to have strong near-infrared localized surface plasmon resonance
      (LSPR) properties originating from the holes in the valence band, and also
      catalytic activity of more than a 500-fold enhancement of chemiluminescence (CL)
      in a luminol-H2O2 system. Investigations into the mechanisms behind these results
      showed that the high concentration of free carriers in Cu(2-x)Se NCs, which are
      derived from their high copper deficiencies that make Cu(2-x)Se NCs both good
      electron donors and acceptors with high ionic mobility, could greatly enhance the
      catalytic ability of Cu(2-x)Se NCs to facilitate electron-transfer processes and
      the decomposition of H2O2 into OH and O2(-), which are the commonly accepted key
      intermediates in luminol CL enhancement. Thus, it can be concluded that
      controllable copper deficiencies that are correlated with their near-infrared
      LSPR are critically responsible for the effective catalysis of Cu(2-x)Se NCs in
      the enhanced CL.

PMID- 25065364
TI  - Liver and gender: are there differences in fibrous tissue before the onset of
      fibrosis?

PMID- 25065366
TI  - A medium-throughput analysis of signaling pathways involved in early stages of
      stem cell reprogramming.
AB  - The induction of pluripotency from adult cells has enormous potential in
      regenerative medicine. While initial efforts to study mechanisms and improve
      efficiency of induced pluripotent stem cell (iPSC) reprogramming focused on the
      direct roles of transcriptional regulators, increasing evidence indicates that
      cellular signal transduction pathways can modulate this process. Here, we present
      a medium-throughput system to study the effect of signaling pathways on the early
      stages of reprogramming. We generated a set of lentiviral vectors encoding 38
      genes that upregulate or downregulate major signal transduction pathways and
      quantified each signaling factor's effect on reprogramming. This approach
      confirmed the role of several factors previously implicated in reprogramming, as
      well as identified several GTPases-factors that to date have not been largely
      studied in reprogramming-that improve or hinder iPSC reprogramming. In addition,
      this methodology is useful in determining new targets for enhancing pluripotency
      reprogramming, lineage reprogramming, and/or cell differentiation.

PMID- 25065367
TI  - Determination of a novel phosphodiesterase4 inhibitor, 3-[1-(3cyclopropylmethoxy
      4-difluoromethoxybenzyl)-1H-pyrazol-3-yl]-benzoic acid (PDE-423) in rat plasma
      using liquid chromatography-tandem mass spectrometry.
AB  - A method for determining a novel phosphodiesterase-4 inhibitor, 3-[1
      (3cyclopropylmethoxy-4-difluoromethoxybenzyl)-1H-pyrazol-3-yl]-benzoic acid (PDE
      423), in rat plasma was developed and validated using liquid chromatography
      tandem mass spectrometry for further pharmacokinetic study for development as a
      novel anti-asthmatic drug. PDE-423 in the concentration range of 0.02-10 ug/mL
      was linear with a correlation coefficient of >0.99, and the mean intra- and inter
      assay precisions of the assay were 7.50 and 3.86%, respectively. The validated
      method was used successfully for a pharmacokinetic study of PDE-423 in rats.

PMID- 25065368
TI  - High prevalence of iron deficiency in patients with acute decompensated heart
      failure.
AB  - AIMS: Limited data are available on iron parameters in patients hospitalized for
      decompensation of chronic heart failure. METHODS AND RESULTS: Iron parameters of
      patients hospitalized for decompensation of chronic heart failure were
      prospectively assessed during the 72 h after hospital admission. Iron deficiency
      was defined according to the 2012 European Society of Cardiology Guidelines.
      Overall, 411 men (75 +/- 12  years; 75% NYHA functional classes III/IV) and 421
      women (81 +/- 11 years; 71% NYHA classes III/IV) were evaluated. The prevalence
      of iron deficiency was 69% in men and 75% in women (including 41% and 49% with
      absolute iron deficiency, respectively). The prevalence of anaemia in men (<13
      g/dL) was 68% and in women (<12 g/dL) it was 52%. Among non-anaemic patients, the
      prevalence of iron deficiency was 57% in men and 79% in women. Only 9% of
      patients received iron supplementation at the time of admission (oral, 9%;
      intravenous, 0.2%). Multivariate analysis showed that anaemia and antiplatelet
      treatment in men, and diabetes and low C-reactive protein in women, were
      independently associated with iron deficiency. CONCLUSIONS: Iron deficiency is
      very common in patients admitted for acute decompensated heart failure, even
      among non-anaemic patients. Given the benefit of iron therapy in chronic heart
      failure, our results emphasize the need to assess iron status not only in chronic
      heart failure patients, but even more so in those admitted for worsening heart
      failure, regardless of gender, heart failure severity, or haemoglobin level.
      Initiating iron therapy in hospitalized heart failure patients needs to be
      investigated.

PMID- 25065369
TI  - A first-principles investigation on microscopic atom distribution and
      configuration-averaged properties in Cd(1-x)Zn(x)S solid solutions.
AB  - The structural, energetic, and electronic properties of zincblende and wurtzite
      phase Cd(1-x)Zn(x)S (0<=x<=1) solid solutions were investigated by first
      principles calculations. It was revealed that the trend of atom distribution in
      configurations with the same x value can be quantitatively characterized by the
      average length of the Zn-S bonds. The origin of this trend was attributed to the
      strong interaction of the Zn-S bonds, which acted against the aggregation of Zn
      atoms in this solid solution. By using a configuration-averaged method,
      structural and energetic properties were estimated as a function of Zn content at
      the level of the generalized gradient approximation, whereas electronic
      properties were corrected by using a hybrid functional. Phase diagrams of both
      solid solutions were established. An optimal x value of approximately 0.5 for
      photocatalytic hydrogen production was determined by taking both the band edges
      and band gaps into consideration; this conclusion was supported by the results of
      a variety of experiments.

PMID- 25065371
TI  - In vivo HIV-1 hypermutation and viral loads among antiretroviral-naive Brazilian
      patients.
AB  - Hypermutation alludes to an excessive number of specific guanine-to-adenine (G-
      >A) substitutions in proviral DNA and this phenomenon is attributed to the
      catalytic activity of cellular APOBECs. Population studies relating hypermutation
      and the progression of infection by human immunodeficiency virus type 1 (HIV-1)
      have been performed to elucidate the effect of hypermutation on the natural
      course of HIV-1 infection. However, the many different approaches employed to
      assess hypermutation in nucleotide sequences render the comparison of results
      difficult. This study selected 157 treatment-naive patients and sought to
      correlate the hypermutation level of the proviral sequences in clinical samples
      with demographic variables, HIV-1 RNA viral load, and the level of CD4(+) T
      cells. Nested touchdown polymerase chain reaction (PCR) was performed with
      specific primers to detect hypermutation in the region of HIV-1 integrase, and
      the amplified sequences were run in agarose gels with HA-Yellow. The analysis of
      gel migration patterns using the k-means clustering method was validated by its
      agreement with the results obtained with the software Hypermut. Hypermutation was
      found in 31.2% of the investigated samples, and a correlation was observed
      between higher hypermutation levels and higher viral load levels. These findings
      suggest a high frequency of hypermutation detection in a Brazilian cohort, which
      can reflect a particular characteristic of this population, but also can result
      from the method approach by aiming at hypermutation-sensitive sites. Furthermore,
      we found that hypermutation events are pervasive during HIV-1 infection as a
      consequence of high viral replication, reflecting its role during disease
      progression.

PMID- 25065372
TI  - Childhood abuse and neglect in relation to the presence and persistence of
      psychotic and depressive symptomatology.
AB  - BACKGROUND: The association between childhood trauma and psychotic and depressive
      symptomatology is well established. However, less is known about the specificity
      and course of these symptoms in relation to childhood trauma. METHOD: In a large
      sample (n = 2765) of patients with psychosis (n = 1119), their siblings (n =
      1057) and controls (n = 589), multivariate (mixed-effects) regression analyses
      with multiple outcomes were performed to examine the association between
      childhood trauma and psychotic and depressive symptomatology over a 3-year
      period. RESULTS: A dose-response relationship was found between childhood trauma
      and psychosis. Abuse was more strongly associated with positive symptoms than
      with negative symptoms whereas the strength of the associations between neglect
      and positive and negative symptoms was comparable. In patients, similar
      associations between childhood trauma and psychotic or depressive symptoms were
      found, and in siblings and controls, stronger associations were found between
      trauma and depressive symptomatology. Childhood trauma was not related to a
      differential course of symptoms over a 3-year time period. CONCLUSIONS: In
      congruence with earlier work, our findings suggest that childhood trauma, and
      abuse in particular, is associated with (subthreshold) psychosis. However,
      childhood trauma does not seem to be associated with a differential course of
      symptoms, nor does it uniquely heighten the chance of developing (subthreshold)
      psychotic symptomatology. Our results indicate that trauma may instead contribute
      to a shared vulnerability for psychotic and depressive symptoms.

PMID- 25065370
TI  - Molecular and cellular neuroinflammatory status of mouse brain after systemic
      lipopolysaccharide challenge: importance of CCR2/CCL2 signaling.
AB  - BACKGROUND: Genetic and environmental factors are critical elements influencing
      the etiology of major depression. It is now accepted that neuroinflammatory
      processes play a major role in neuropsychological disorders. Neuroinflammation
      results from the dysregulation of the synthesis and/or release of pro- and anti
      inflammatory cytokines with central or peripheral origin after various insults.
      Systemic bacterial lipopolysaccharide (LPS) challenge is commonly used to study
      inflammation-induced depressive-like behaviors in rodents. In the present study,
      we investigated immune-to-brain communication in mice by examining the effects of
      peripheral LPS injection on neuroinflammation encompassing cytokine and chemokine
      production, microglia and central nervous system (CNS)-associated phagocyte
      activation, immune cell infiltration and serotonergic neuronal function. METHODS:
      LPS was administered to C57BL/6 J mice by intraperitoneal injection; brains were
      collected and pro-inflammatory cytokine mRNA and proteins were measured. To
      examine the relative contribution of the different populations of brain immune
      cells to the occurrence of neuroinflammation after acute systemic inflammation,
      we precisely characterized them by flow cytometry, studied changes in their
      proportions and level of activation, and measured the amount of cytokines they
      released by Cytometric Bead ArrayTM after cell sorting and ex vivo culture.
      Because of the central role that the chemokine CCL2 seems to play in our
      paradigm, we studied the effect of CCL2 on the activity of serotonergic neurons
      of the raphe nucleus using electrophysiological recordings. RESULTS: We report
      that systemic LPS administration in mice caused a marked increase in pro
      inflammatory IL-1beta, IL-6, TNFalpha and CCL2 (monocyte chemoattractant protein
      1) mRNA and protein levels in the brain. Moreover, we found that LPS caused
      microglia and CNS-associated phagocyte activation characterized by upregulation
      of CCR2, TLR4/CD14, CD80 and IL-4Ralpha, associated with overproduction of pro
      inflammatory cytokines and chemokines, especially CCL2. LPS also induced a marked
      and selective increase of CCR2(+) inflammatory monocytes within the brain.
      Finally, we showed that CCL2 hyperpolarized serotonergic raphe neurons in mouse
      midbrain slices, thus probably reducing the serotonin tone in projection areas.
      CONCLUSION: Together, we provide a detailed characterization of the molecular and
      cellular players involved in the establishment of neuroinflammation after
      systemic injection of LPS. This highlights the importance of the CCL2/CCR2
      signaling and suggests a possible link with depressive disorders.

PMID- 25065373
TI  - Impact of stress on different components of impulsivity in borderline personality
      disorder.
AB  - BACKGROUND: Previous research on impulsivity in borderline personality disorder
      (BPD) has revealed inconsistent findings. Impulsive behaviour is often observed
      during states of emotional distress and might be exaggerated by current attention
      deficit hyperactivity disorder (ADHD) symptoms in individuals with BPD. We aimed
      to investigate different components of impulsivity dependent on stress induction
      controlling for self-reported ADHD symptoms in BPD. METHOD. A total of 31
      unmedicated women with BPD and 30 healthy women (healthy controls; HCs), matched
      for age, education and intelligence, completed self-reports and behavioural tasks
      measuring response inhibition (go/stop task) and feedback-driven decision making
      (Iowa Gambling Task) under resting conditions and after experimental stress
      induction. ADHD symptoms were included as a covariate in the analyses of
      behavioural impulsivity. Additionally, self-reported emotion-regulation
      capacities were assessed. RESULTS: BPD patients reported higher impulsive traits
      than HCs. During stress conditions - compared with resting conditions - self
      reported impulsivity was elevated in both groups. Patients with BPD reported
      higher state impulsivity under both conditions and a significantly stronger
      stress-dependent increase in state impulsivity. On the behavioural level, BPD
      patients showed significantly impaired performance on the go/stop task under
      stress conditions, even when considering ADHD symptoms as a covariate, but not
      under resting conditions. No group differences on the Iowa Gambling Task were
      observed. Correlations between impulsivity measures and emotion-regulation
      capacities were observed in BPD patients. CONCLUSIONS: Findings suggest a
      significant impact of stress on self-perceived state impulsivity and on response
      disinhibition (even when considering current ADHD symptoms) in females with BPD.

PMID- 25065374
TI  - Increased severity of suicidal behavior in impulsive aggressive patients exposed
      to familial adversities.
AB  - BACKGROUND: The mechanisms by which childhood abuse and family history of
      suicidal behavior (FHS) lead to an increased risk of suicidal behavior are still
      unknown. Impulsive aggression may play an intermediate role. We investigated
      whether greater scores for aggression and impulsivity might be associated with
      the effects of FHS and/or childhood abuse on the severity of suicidal behavior.
      METHOD: We examined the scores of three scales measuring impulsive aggression in
      a sample of 696 suicide attempters. We compared the highest and lowest scores
      with regard to reports of childhood abuse and FHS using adjusted multinomial
      regression models. Genetic polymorphisms of the serotonergic system known to be
      associated with impulsive aggression were also analyzed. RESULTS: Patients with
      high impulsive aggressive scores showed significant differences in
      sociodemographic, clinical and suicidal features compared with patients with low
      impulsive aggressive scores. Adjusted results showed that combinations of some
      types of childhood abuse and FHS, particularly emotional abuse and emotional
      neglect, are associated with high impulsivity and hostility scores. The SS
      genotype of the serotonin transporter gene (5-HTTLPR) was associated with high
      levels of impulsivity when the subjects reported emotional abuse [odds ratio (OR)
      5.55, 95% confidence interval (CI) 1.75-17.5] or physical abuse (OR 5.03, 95% CI
      1.50-16.9) in their childhood. CONCLUSIONS: Our results support the role of
      impulsive aggression as one of the links that may connect childhood abuse and FHS
      with severity of suicidal behavior.

PMID- 25065375
TI  - Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general
      population: Mendelian randomization study.
AB  - BACKGROUND: Low plasma 25-hydroxyvitamin D [25(OH)D] levels are associated with
      high cardiovascular risk. This may be because that low 25(OH)D levels are
      associated with high levels of atherogenic lipoproteins, but whether these 2 risk
      factors are genetically associated is unknown. We tested this hypothesis. METHODS
      AND RESULTS: Using a Mendelian randomization approach, potential genetic
      associations between plasma levels of atherogenic lipoproteins and 25(OH)D were
      examined in <=85,868 white, Danish individuals in whom we genotyped for variants
      affecting plasma levels of 25(OH)D, nonfasting remnant cholesterol, low-density
      lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein
      levels were measured in all and 25(OH)D levels in 31,435. A doubling in
      nonfasting remnant cholesterol levels was observationally and genetically
      associated with -6.0%(95% confidence interval [CI], -6.5% to -5.5%) and -8.9%
      (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein
      cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%)
      observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a
      halving in high-density lipoprotein-cholesterol levels was observationally
      associated with -1.5% (95% CI, -2.2% to -0.7%) lower but genetically associated
      with +20% (95% CI, +7.4% to +34%) higher plasma 25(OH)D levels. Plasma levels of
      lipoprotein(a) and 25(OH)D did not associate. Finally, low 25(OH)D levels did not
      associate genetically with levels of remnant and low-density lipoprotein
      cholesterol. CONCLUSIONS: Genetically elevated nonfasting remnant cholesterol is
      associated with low 25(OH)D levels, whereas genetically reduced high-density
      lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings
      suggest that low 25(OH)D levels observationally is simply a marker for elevated
      atherogenic lipoproteins and question a role for vitamin D supplementation in the
      prevention of cardiovascular disease.

PMID- 25065376
TI  - Sunlight exposure during leisure activities and risk of prostate cancer in
      Montreal, Canada, 2005-2009.
AB  - BACKGROUND: Prostate cancer (PCa) is the leading cause of cancer in men in many
      developed countries, but no modifiable risk factors have been identified. A
      handful of analytical studies have suggested a possible etiological role for
      sunlight exposure. We report here on the association between leisure-time
      sunlight exposure during adulthood and PCa risk in the context of a population
      based case-control study. METHODS: In all, 1,904 PCa cases were ascertained
      across Montreal French hospitals between 2005 and 2009. Concurrently, 1,962
      population controls, frequency matched to cases by age (+/-5 years), were
      selected from the electoral list for French-speakers in Greater Montreal.
      Interviews elicited the frequency of engagement in any leisure activity during
      adulthood. This was used to derive cumulative sunlight exposure indices: a
      cumulative number of leisure activities events entailing sunlight exposure and a
      cumulative duration of sunlight exposure during leisure activities. Unconditional
      logistic regression was conducted to yield odds ratios (OR) and 95% confidence
      intervals (CI) for estimating the association between sunlight exposure indices
      and PCa risk, adjusting for age, ancestry, family history of PCa, PCa screening,
      education, solar protection, body mass index and physical activity. RESULTS:
      Compared with men in the upper quartile category for the number of sunlight
      exposure events, men never exposed during leisure time had an OR of 1.32 (95% CI:
      0.82-2.14). ORs were 1.11, 0.91 and 1.00 for the first to the third quartiles of
      exposure, respectively. Similar results were observed for cumulative duration of
      exposure to sunlight, and by PCa aggressiveness. CONCLUSION: These findings
      provide little evidence of an association between sunlight exposure during
      leisure-time and PCa risk. Men with no sunlight exposure appeared at somewhat
      higher risks but none of the estimates achieved statistical significance.

PMID- 25065377
TI  - ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in
      schizophrenia and healthy subjects.
AB  - BACKGROUND: Genetic variation in the gene encoding ZNF804A, a risk gene for
      schizophrenia, has been shown to affect brain functional endophenotypes of the
      disorder, while studies of white matter structure have been inconclusive. METHOD:
      We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey
      and white matter using voxel-based morphometry (VBM) in high-resolution T1
      weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54
      matched healthy controls. RESULTS: We found a significant (p < 0.05, family-wise
      error corrected for multiple comparisons) interaction effect of diagnostic group
      x genotype for local grey matter in the left orbitofrontal and right and left
      lateral temporal cortices, where patients and controls showed diverging effects
      of genotype. Analysing the groups separately (at p < 0.001, uncorrected),
      variation in rs1344706 showed effects on brain structure within the schizophrenia
      patients in several areas including the left and right inferior temporal, right
      supramarginal/superior temporal, right and left inferior frontal, left
      frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and
      the right thalamus, as well as effects within the healthy controls in left
      lateral temporal, right anterior insula and left orbitofrontal cortical areas. We
      did not find effects of genotype of regional white matter in either of the two
      cohorts. CONCLUSIONS: Our findings demonstrate effects of ZNF804A genetic
      variation on brain structure, with diverging regional effects in schizophrenia
      patients and healthy controls in frontal and temporal brain areas. These effects,
      however, might be dependent on the impact of other (genetic or non-genetic)
      disease factors.

PMID- 25065378
TI  - Wanted: pediatric nephrologists! - why trainees are not choosing pediatric
      nephrology.
AB  - A workforce crisis for many pediatric specialties, particularly nephrology, is
      due to growing retirement rates, attrition during training, and retention
      difficulties. To obtain specific information regarding pediatric nephrology
      trainee shortages, we administered two cross-sectional surveys to non-renal
      pediatric subspecialty fellows and pediatric nephrology program directors. We
      characterized the fellows' experiences with nephrology and the program directors'
      experiences with their fellows as well as their outcomes in the last 10 years. We
      analyzed responses from 531 non-renal fellows (14.4% response rate). Overall, 317
      (60%) fellows rated nephrology as difficult, particularly women (65.4% vs. 49.5%,
      p < 0.001), with American women medical graduates rating nephrology as more
      difficult compared to all others (p = 0.001). More men than women (24% vs. 8%, p
      < 0.001) considered the monetary benefit as not adequate. Program directors (25;
      64% response rate) represented 57% of all USA fellows in training, and 15 (60%)
      found it difficult to recruit qualified applicants. Of the 183 graduates in the
      past 10 years, 35 (19%) were reported as not in the USA pediatric nephrology
      workforce. These findings support our belief that a strong effort needs to be
      made by the academic community to teach nephrology in more interesting and
      understandable formats. While these are national samples, we were unable to
      contact non-nephrology fellows directly and program directors from larger
      programs were underrepresented. Difficulties in attracting/retaining trainees
      (particularly women) to nephrology must be addressed systematically, identifying
      incentives to practice in this field. Bold concerted efforts are required and we
      propose seven steps to achieve this goal.

PMID- 25065379
TI  - A gender-based comparison of pain tolerance during pulsed dye laser therapy.
AB  - BACKGROUND: Cosmetic laser treatments are frequently performed without anesthesia
      in the clinic setting and there is a need to better understand the factors that
      may impact patient pain levels during these procedures. There has been prior
      research suggesting that there are significant gender-based differences in pain
      experiences with a variety of interventions. AIMS: We sought to examine the
      influence of gender and specific emotional factors on pain perception during
      pulsed dye laser treatments. PATIENTS/METHODS: We conducted a questionnaire-based
      study of 84 adult patients (42 males and 42 females) who underwent facial pulsed
      dye laser treatments in our clinic for cosmetic purposes. Questionnaires were
      completed by each patient after his or her initial laser treatment and patients
      were queried as to their perceived levels of pain during the procedure.
      Additional information regarding quality of life measures and patient motivation
      was also collected. RESULTS: Contrary to prior research suggesting lower pain
      thresholds for women in other clinical or experimental settings, we found no
      statistically significant differences in mean pain levels reported between
      patients of each gender. There was a trend toward females being somewhat more
      likely than males to see the pain of the treatment as justified for an
      improvement in appearance. CONCLUSIONS: Patient motivation and pain tolerance
      levels may be similar between genders among patients undergoing non-invasive
      cosmetic procedures. Clinicians may, therefore, expect patients of either gender
      to tolerate such treatments equally well.

PMID- 25065380
TI  - Use of micro-focused ultrasound with visualization to lift and tighten lax knee
      skin (1.).
AB  - INTRODUCTION: Public interest in noninvasive, aesthetic treatments for the
      rejuvenation of appearance continues to grow. The following prospective, open
      label, nonrandomized trial was conducted to evaluate the safety and efficacy of
      micro-focused ultrasound with visualization (MFU-V) for achieving lift and
      tightening of lax skin above the knee. MATERIALS AND METHODS: Healthy adult women
      (N = 30) with mild- to moderate bilateral skin laxity above the knees were
      enrolled. MFU-V was applied to a grid of eight 25 mm(2) squares above each knee.
      MFU-V was first applied using a 4 MHz, 4.5 mm transducer followed by a 7 MHz, 3.0
      mm transducer. Approximately 320 treatment lines applied to each knee
      [corrected]. The primary efficacy endpoint was lifting and tightening of lax skin
      above the knee as determined by the principle investigator using the Physician
      Global Aesthetic Improvement Scale (PGAIS). RESULTS: Among 28 evaluable subjects,
      24 subjects (86%) showed improved lifting and tightening of knee skin laxity at
      90- and 180-day follow-up visits. Three subjects showed no change and the
      appearance of one subject worsened. There were no adverse events or evidence of
      skin injury. CONCLUSION: Similar to its safety and efficacy for tightening facial
      skin and reducing wrinkles, MFU-V is an effective, noninvasive method for
      reducing skin laxity and improving the appearance of skin above the knee.
      ClinicalTrials.gov Identifier: NCT01708434.

PMID- 25065381
TI  - Evaluation of effects of platelet-rich plasma on human facial skin.
AB  - INTRODUCTION: Platelet-rich plasma (PRP) has been used for rapid healing and
      tissue regeneration in many fields of medicine. This study was conducted to
      evaluate the effects of PRP application procedure on human facial skin. METHODS:
      PRP was applied thrice at 2-week intervals on the face of ten healthy volunteers.
      It was applied to individual's forehead, malar area, and jaw by a dermaroller,
      and injected using a 27-gauge injector into the wrinkles of crow's feet.
      Participants were asked to grade on a scale from 0 to 5 for general appearance,
      skin firmness-sagging, wrinkle state and pigmentation disorder of their own face
      before each PRP procedure and 3 months after the last PRP procedure. While
      volunteers were evaluating their own face, they were also assessed by three
      different dermatologists at the same time by the same five-point scale. RESULTS:
      There was statistically significant difference regarding the general appearance,
      skin firmness-sagging and wrinkle state according to the grading scale of the
      patients before and after three PRP applications. Whereas there was only
      statistically significant difference for the skin firmness-sagging according to
      the assessment of the dermatologists. CONCLUSION: PRP application could be
      considered as an effective procedure for facial skin rejuvenation.

PMID- 25065382
TI  - Facile one-pot preparation of chitosan/calcium pyrophosphate hybrid microflowers.
AB  - Flower-like chitosan/calcium pyrophosphate hybrid microparticles (microflowers)
      are prepared using a facile one-pot approach by combining ionotropic gelation
      with biomimetic mineralization. Chitosan-tripolyphosphate (CS-TPP) nanocomplexes
      are first synthesized through ionotropic gelation; meanwhile, excess TPP is
      partly hydrolyzed into pyrophosphate ions (P2O7(4-)). Upon addition of CaCl2, CS
      TPP nanocomplexes serve as a versatile template, inducing in situ mineralization
      of Ca2P2O7 and directing its growth and assembly into microflowers. The whole
      preparation process can be completed within half an hour. The as-prepared
      microflowers are composed of 23.0% CS-TPP nanocomplexes and 77.0% Ca2P2O7
      crystals. Mesopores (3.7 and 11.2 nm) and macropores coexist in the microflowers,
      indicating porous and hierarchical structures. The microflowers exhibit high
      efficiency in dye adsorption and enzymatic catalysis. Specifically, a high
      adsorption capacity of 520 mg g(-1) for Congo red is achieved. And the
      immobilized enzyme retains about 85% catalytic activity compared with that of the
      free enzyme. The facile one-pot preparation process ensures the broad
      applications of the porous hybrid microflowers. 

PMID- 25065384
TI  - RNA interference for the identification of ectoparasite vaccine candidates.
AB  - Ectoparasites present a major challenge for disease management globally. With
      drug resistance increasingly observed in many disease-causing species, the need
      for novel control measures is pressing. Ever-expanding genomic resources from
      'next generation' sequencing are now available for a number of arthropod
      ectoparasites, necessitating an effective means of screening these data for novel
      candidates for vaccine antigens or targets for chemotherapeutics. Such in vitro
      screening methods must be developed if we are to make discoveries in a timely and
      cost-effective manner. This review will discuss the potential that RNA
      interference (RNAi) has demonstrated thus far in the context of arthropod
      ectoparasites and the potential roles for this technology in the development of
      novel methods for parasite control. 

PMID- 25065385
TI  - Threading plasmonic nanoparticle strings with light.
AB  - Nanomaterials find increasing application in communications, renewable energies,
      electronics and sensing. Because of its unsurpassed speed and highly tuneable
      interaction with matter, using light to guide the self-assembly of nanomaterials
      can open up novel technological frontiers. However, large-scale light-induced
      assembly remains challenging. Here we demonstrate an efficient route to nano
      assembly through plasmon-induced laser threading of gold nanoparticle strings,
      producing conducting threads 12+/-2 nm wide. This precision is achieved because
      the nanoparticles are first chemically assembled into chains with rigidly
      controlled separations of 0.9 nm primed for re-sculpting. Laser-induced threading
      occurs on a large scale in water, tracked via a new optical resonance in the near
      infrared corresponding to a hybrid chain/rod-like charge transfer plasmon. The
      nano-thread width depends on the chain mode resonances, the nanoparticle size,
      the chain length and the peak laser power, enabling nanometre-scale tuning of the
      optical and conducting properties of such nanomaterials. 

PMID- 25065386
TI  - Wide QRS tachycardia: what is the mechanism?

PMID- 25065387
TI  - Weak crossability barrier but strong juvenile selection supports ecological
      speciation of the hybrid pine Pinus densata on the Tibetan plateau.
AB  - Determining how a new hybrid lineage can achieve reproductive isolation is a key
      to understanding the process and mechanisms of homoploid hybrid speciation. Here,
      we evaluated the degree and nature of reproductive isolation between the
      ecologically successful hybrid species Pinus densata and its parental species P.
      tabuliformis and P. yunnanensis. We performed interspecific crosses among the
      three species to assess their crossability. We then conducted reciprocal
      transplantation experiments to evaluate their fitness differentiation, and to
      examine how natural populations representing different directions of
      introgression differ in adaptation. The crossing experiments revealed weak
      genetic barriers among the species. The transplantation trials showed manifest
      evidence of local adaptation as the three species all performed best in their
      native habitats. Pinus densata populations from the western edge of its
      distribution have evolved a strong local adaptation to the specific habitat in
      that range; populations representing different directions of introgressants with
      the two parental species all showed fitness disadvantages in this P. densata
      habitat. These observations illustrate that premating isolation through selection
      against immigrants from other habitat types or postzygotic isolation through
      selection against backcrosses between the three species is strong. Thus,
      ecological selection in combination with endogenous components and geographic
      isolation has likely played a significant role in the speciation of P. densata. 

PMID- 25065388
TI  - Dimensionality and stages of severity of DSM-5 criteria in an international
      sample of alcohol-consuming individuals.
AB  - INTRODUCTION: The DSM-5 alcohol use disorder (AUD) criteria proposal contains 11
      criteria that include most of the DSM-IV abuse and dependence criteria plus
      craving. The aims of the current study in a large and international alcohol
      consuming sample were to confirm the dimensionality of the DSM-5 AUD criteria and
      to differentiate grades of severity of DSM-5 AUD in subjects who pass the
      proposed DSM-5 diagnostic threshold of two criteria. METHOD: We used the World
      Health Organization (WHO)/International Society on Biomedical Research on
      Alcoholism (ISBRA) Study on State and Trait Markers of Alcohol Use and Dependence
      dataset. Subjects included in the analyses were aged >= 18 years and were
      recruited in five countries: Australia, Brazil, Canada, Finland and Japan.
      Assessment of AUD and additional characteristics was conducted using an adapted
      version of the Alcohol Use Disorder and Associated Disabilities Interview
      Schedule (AUDADIS). Dimensionality of the DSM-5 criteria was evaluated using
      factor analysis and item response theory (IRT) models. The IRT results led to the
      classification of AUD patients into three severity groups. External validators
      were used to differentiate statistically across subgroups. RESULTS: A total of
      1424 currently drinking individuals were included in the analyses. Factor and IRT
      analyses confirmed the dimensional structure of DSM-5 AUD criteria. More than 99%
      of the subjects could be allocated to one of the suggested severity subgroups.
      The magnitude of the external validators differed significantly across the
      severity groups. CONCLUSIONS: The results confirm the dimensional structure of
      the proposed DSM-5 AUD criteria. The suggested stages of severity (mild, moderate
      and severe) may be useful to clinicians by grouping individuals not only in the
      mild but also in the moderate to severe spectrum of DSM-5 AUD.

PMID- 25065389
TI  - Stimulating and evaluating acquired knowledge of addiction among residents
      through repeat testing: a pilot study.
AB  - BACKGROUND: Addictive disorders receive little attention in medical school and
      residency program curricula. OBJECTIVE: To evaluate an innovative learning
      approach encouraging and stimulating residents to focus on key competencies by
      testing before and after their addiction psychiatry rotation. METHODS: We
      developed a 50-item test on substance use disorders. Twenty-six general
      psychiatry residents, post-graduate year I (PGY-I) and II (PGY-II), participated
      in the pilot study and were divided into three groups. PGY-I residents were
      divided into Group 1, who were tested the last day of the rotation and again 2
      months later, and Group 2, who were tested on the first and the last day of the
      rotation. Eight of 11 PGY-II residents agreed to participate as controls (Group
      3), as they had previously completed their 2-month addiction psychiatry rotation
      as PGY-I's. All residents were informed that the testing would not affect their
      individual grade. After taking the first test, all three groups received related
      study materials. RESULTS: A statistically significant increase in re-test scores
      occurred in the combined groups (p < .001). The largest changes in scores were
      among Group 2 (the group taking the test on first and last day of their addiction
      psychiatry rotation). CONCLUSION: The greatest learning seemed to occur when
      residents were tested at beginning and end of the rotation. However, all
      residents' test scores improved to some degree, regardless of their level of
      training or the timing of the test. SCIENTIFIC SIGNIFICANCE: This study offers
      support for testing as a learning guide and as a means of stimulating residents'
      learning.

PMID- 25065390
TI  - Immunohistochemical expression of matrix metalloprotease-2 and matrix
      metalloprotease-9 in the disks of patients with temporomandibular joint
      dysfunction.
AB  - PURPOSE: Matrix metalloproteases (MMPs) are tissue-remodeling enzymes that
      function during the remodeling process, such as in immune-inflammatory diseases.
      Metalloprotease-2 (MMP-2) and metalloprotease-9 (MMP-9) are gelatinases that
      degrade several types of extracellular matrix collagen. It is hypothesized that
      in temporomandibular joint (TMJ) dysfunction, MMP-2 and MMP-9 expression levels
      may be elevated. Therefore, the objective of this study is to determine the
      association of MMP-2 and MMP-9 expression with temporomandibular joint
      dysfunction using an immunohistochemical approach to evaluate the joint disk.
      MATERIAL AND METHODS: A total of 45 human temporomandibular joint samples were
      collected, with 36 samples in the test group (patients with anterior disk
      displacement with reduction (n = 29) and without reduction (n = 7)) and nine
      samples in the control group. The immunostaining of the TMJ disks was
      statistically compared between the groups (P < 0.05). RESULTS: There was a
      statistically significant difference for the area of MMP-2 immunostaining between
      the control group and the displacement disks with reduction group (ADDwR) (P =
      0.048) and between the groups with disk displacement and without reduction
      (ADDwoR) (P = 0.029). The expression of MMP-2 was significantly elevated in the
      ADDwoR group. CONCLUSION: No statistically significant difference was found
      between the variable area of MMP-9 expression in the disk with and without disk
      displacement, as determined by immunohistochemical analysis. However, there was
      an elevation of MMP-2 expression in the disks of patients with displacement and
      without reduction (more severe alteration).

PMID- 25065391
TI  - Plaque-like CD34-positive dermal fibroma/medallion-like dermal dendrocyte
      hamartoma: an unusual spindle cell neoplasm.

PMID- 25065393
TI  - Periodontopathogens and human beta-defensin-2 expression in gingival crevicular
      fluid from patients with periodontal disease in Guangxi, China.
AB  - BACKGROUND AND OBJECTIVE: Periodontal diseases are often induced by
      periodontopathogens, which are always exposed to certain innate immune factors in
      gingival crevicular fluid, including human beta-defensin-2 (hBD-2). This study
      aims to investigate the relationship among periodontopathogens, clinical
      parameters and hBD-2 expression. MATERIAL AND METHODS: Thirty-two healthy
      controls, 42 patients with chronic gingivitis and 95 patients with chronic
      periodontitis were recruited in Guangxi, China. Bleeding index, probing depth and
      clinical attachment level were measured for all teeth including mesiobuccal,
      buccal, disobuccal, mesiolingual, lingual, disolingual six sites of all patient.
      Gingival crevicular fluid samples were collected from the study sites. The
      prevalence and copy numbers (CN) of Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Tannerella
      forsythia and total bacteria in gingival crevicular fluid were quantified by real
      time PCR. The hBD-2 concentration in gingival crevicular fluid was measured by
      ELISA. RESULTS: Both the prevalence and the CN of A. actinomycetemcomitans, P.
      gingivalis, T. denticola and T. forsythia were higher in patients with chronic
      periodontitis than in healthy controls and patients with chronic gingivitis;
      however, there was no significant difference in the prevalence of P. intermedia
      among the three study groups, and the highest CN was found in patients with
      chronic gingivitis, rather than in patients with chronic periodontitis. The loads
      of P. gingivalis, P. intermedia, T. denticola and total bacteria were positively
      related to probing depth, bleeding index and clinical attachment level. The
      concentration of hBD-2 in gingival crevicular fluid was higher in patients with
      chronic gingivitis and in patients with chronic periodontitis than in healthy
      controls. In addition, the hBD-2 concentration was positively related to the CN
      of P. gingivalis, T. forsythia and total bacteria, as well as to bleeding index
      and probing depth. CONCLUSION: The prevalence, composition and CN of
      periodontopathogens were closely related to the severity of periodontal disease,
      and the red complex was related to the severity of clinical symptoms of
      periodontal diseases. The concentration of hBD-2 in gingival crevicular fluid
      from periodontal disease sites was higher than that in gingival crevicular fluid
      from healthy sites, which suggests that hBD-2 expression might be up-regulated by
      periodontopathogens.

PMID- 25065394
TI  - Physician perceptions and experience of current treatment in actinic keratosis.
AB  - BACKGROUND: Topical therapy is important in the treatment of actinic keratosis
      (AK), a major risk factor for, and early development stage of, squamous cell
      carcinoma. Despite this, research addressing the limitations and challenges
      associated with topical field therapy in actinic keratosis is lacking.
      OBJECTIVES: The aim of this study was to highlight the challenges associated with
      maximizing compliance in patients receiving topical AK therapy and to investigate
      real-world experience with currently available topical therapies including
      perceptions of adherence and persistence. METHODS: A 45-min online survey was
      developed and completed by physicians in eight countries. All had previously
      prescribed topical AK therapy and >=1 other treatment. Physicians' consensus was
      summarized as overall agreement/disagreement from >=70% of respondents (>=60% for
      case-specific questions). RESULTS: More than 70% of the 427 respondents agreed
      that topical field therapy is essential and had concerns that lengthy treatments
      and local skin reactions caused non-adherence/persistence. More than 90% of
      physicians would preferentially prescribe the shortest duration treatment to such
      patients. CONCLUSIONS: The research clarifies the challenges associated with
      prescribing topical AK therapy and highlights that short treatment duration and
      rapid clearance of skin reactions are key considerations for physicians. This
      provides a basis for the generation of recommendations for improving the real
      world efficacy of topical therapy.

PMID- 25065396
TI  - Positive and negative effects of a threatened parrotfish on reef ecosystems.
AB  - Species that are strong interactors play disproportionately important roles in
      the dynamics of natural ecosystems. It has been proposed that their presence is
      necessary for positively shaping the structure and functioning of ecosystems. We
      evaluated this hypothesis using the case of the world's largest parrotfish
      (Bolbometopon muricatum), a globally imperiled species. We used direct
      observation, animal tracking, and computer simulations to examine the diverse
      routes through which B. muricatum affects the diversity, dispersal, relative
      abundance, and survival of the corals that comprise the foundation of reef
      ecosystems. Our results suggest that this species can influence reef building
      corals in both positive and negative ways. Field observation and simulation
      outputs indicated that B. muricatum reduced the abundance of macroalgae that can
      outcompete corals, but they also feed directly on corals, decreasing coral
      abundance, diversity, and colony size. B. muricatum appeared to facilitate coral
      advancement by mechanically dispersing coral fragments and opening up bare space
      for coral settlement, but they also damaged adult corals and remobilized a large
      volume of potentially stressful carbonate sediment. The impacts this species has
      on reefs appears to be regulated in part by its abundance-the effects of B.
      muricatum were more intense in simulation scenarios populated with high densities
      of these fish. Observations conducted in regions with high and low predator
      (e.g., sharks) abundance generated results that are consistent with the
      hypothesis that these predators of B. muricatum may play a role in governing
      their abundance; thus, predation may modulate the intensity of the effects they
      have on reef dynamics. Overall our results illustrate that functionally unique
      and threatened species may not have universally positive impacts on ecosystems
      and that it may be necessary for environmental managers to consider the diverse
      effects of such species and the forces that mediate the strength of their
      influence.

PMID- 25065395
TI  - Roscovitine is a proteostasis regulator that corrects the trafficking defect of
      F508del-CFTR by a CDK-independent mechanism.
AB  - BACKGROUND AND PURPOSE: The most common mutation in cystic fibrosis (CF),
      F508del, causes defects in trafficking, channel gating and endocytosis of the CF
      transmembrane conductance regulator (CFTR) protein. Because CF is an orphan
      disease, therapeutic strategies aimed at improving mutant CFTR functions are
      needed to target the root cause of CF. EXPERIMENTAL APPROACH: Human CF airway
      epithelial cells were treated with roscovitine 100 MUM for 2 h before CFTR
      maturation, expression and activity were examined. The mechanism of action of
      roscovitine was explored by recording the effect of depleting endoplasmic
      reticulum (ER) Ca(2+) on the F508del-CFTR/calnexin interaction and by measuring
      proteasome activity. KEY RESULTS: Of the cyclin-dependent kinase (CDK) inhibitors
      investigated, roscovitine was found to restore the cell surface expression and
      defective channel function of F508del-CFTR in human CF airway epithelial cells.
      Neither olomoucine nor (S)-CR8, two very efficient CDK inhibitors, corrected
      F508del-CFTR trafficking demonstrating that the correcting effect of roscovitine
      was independent of CDK inhibition. Competition studies with inhibitors of the ER
      quality control (ERQC) indicated that roscovitine acts on the calnexin pathway
      and on the degradation machinery. Roscovitine was shown (i) to partially inhibit
      the interaction between F508del-CFTR and calnexin by depleting ER Ca(2+) and (ii)
      to directly inhibit the proteasome activity in a Ca(2+) -independent manner.
      CONCLUSIONS AND IMPLICATIONS: Roscovitine is able to correct the defective
      function of F508del-CFTR by preventing the ability of the ERQC to interact with
      and degrade F508del-CFTR via two synergistic but CDK-independent mechanisms.
      Roscovitine has potential as a pharmacological therapy for CF.

PMID- 25065398
TI  - The danger of using a sledgehammer to crack a nut: ROTEM-guided administration of
      recombinant activated factor VII in a patient with refractory bleeding post
      ventricular assist device implantation.
AB  - Recombinant activated factor VII (rFVIIa) is currently approved for treating or
      preventing hemorrhage in patients with hemophilia, Glanzmann's thrombasthenia, or
      congenital FVII deficiency. Its "off-label" use for massive bleeding in the
      setting of trauma or surgery has been increasing because of demonstrated
      efficacy. However, the use of rFVIIa also carries a high thrombo-embolic risk.
      This is particularly true in cardiac surgery patients, especially those treated
      with mechanical circulatory support. We describe the case of a patient treated
      with a biventricular assist device in our center, in whom severe bleeding was
      treated in a targeted manner, using rotational thromboelastometry to guide
      administration and dosing of rFVIIa. A comprehensive review of the emerging
      literature on the use of rFVIIa postventricular assist device implantation
      accompanies the case to highlight the need for careful selection of prohemostatic
      agents in this high-risk group. 

PMID- 25065399
TI  - Anti-dementia drugs in a psychiatric hospital for dementia patients.

PMID- 25065400
TI  - Idiopathic basal ganglia calcification as a differential diagnosis of
      parkinsonism: a case report in an older adult.

PMID- 25065397
TI  - Genome-wide screening for DNA variants associated with reading and language
      traits.
AB  - Reading and language abilities are heritable traits that are likely to share some
      genetic influences with each other. To identify pleiotropic genetic variants
      affecting these traits, we first performed a genome-wide association scan (GWAS)
      meta-analysis using three richly characterized datasets comprising individuals
      with histories of reading or language problems, and their siblings. GWAS was
      performed in a total of 1862 participants using the first principal component
      computed from several quantitative measures of reading- and language-related
      abilities, both before and after adjustment for performance IQ. We identified
      novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P
      ~ 10(-7) for each SNP), located respectively at the CCDC136/FLNC and RBFOX2
      genes. Each of these SNPs then showed evidence for effects across multiple
      reading and language traits in univariate association testing against the
      individual traits. FLNC encodes a structural protein involved in cytoskeleton
      remodelling, while RBFOX2 is an important regulator of alternative splicing in
      neurons. The CCDC136/FLNC locus showed association with a comparable
      reading/language measure in an independent sample of 6434 participants from the
      general population, although involving distinct alleles of the associated SNP.
      Our datasets will form an important part of on-going international efforts to
      identify genes contributing to reading and language skills. 

PMID- 25065401
TI  - Central benzodiazepine receptor imaging in Alzheimer's disease with
      cerebrovascular disease.

PMID- 25065402
TI  - Association of hearing loss with behavioral and psychological symptoms in
      patients with dementia.

PMID- 25065403
TI  - Associated factors with gender gap in life expectancy: recommendation for the use
      of healthy life expectancy.

PMID- 25065404
TI  - Neuromodulation of perineally transposed antropylorus with pudendal nerve
      anastomosis following total anorectal reconstruction in humans.
AB  - BACKGROUND: We have reported perineal antropyloric segment transposition with its
      pudendal innervation as a replacement for anal sphincter. Our aim herein was to
      neuromodulate this segment by electrical stimulation. METHODS: Eight patients
      with a permanent colostomy underwent perineal antropyloric segment transposition
      followed by neural anastomosis of its anterior vagus branch to pudendal nerve
      branch in the perineum. Perineal antropyloric graft was assessed for its
      functional integrity and electrophysiological effects. Nerve stimulation was done
      by surface stimulation technique, using a customized stimulation protocol for
      smooth muscle. Antral pressures were recorded on voluntary attempts and on nerve
      stimulation with simultaneous concentric needle electromyography of the perineal
      antropylorus. KEY RESULTS: The antral segment showed slow spontaneous
      contractions (2-3/min) on digital examination, endoscopy, and electrophysiology.
      Stimulated antropyloric electromyography showed a latency of 2-5 s with a
      differential rise in amplitude (mean range 58.57-998.75 MUV) according to the
      frequency of stimulation (range 10-150 Hz). An average latency of 10 s in
      relation to rise in the antral pressure was observed on pudendal nerve
      stimulation. Triggering of the intrinsic rhythm was observed in patients where it
      was initially absent. Voluntary attempts at contraction also showed a rise in
      perineally transposed antral pressure. CONCLUSIONS & INFERENCES: Spontaneous
      rhythm, its generation after electrical stimulation, and response to voluntary
      contraction demonstrates the viability and functional reinnervation of the
      perineally transposed antropyloric segment. Rise in pressure on electrical
      stimulation shows evidence for its neuromodulation.

PMID- 25065405
TI  - Mitochondrial dynamics regulate melanogenesis through proteasomal degradation of
      MITF via ROS-ERK activation.
AB  - Mitochondrial dynamics control mitochondrial functions as well as their
      morphology. However, the role of mitochondrial dynamics in melanogenesis is
      largely unknown. Here, we show that mitochondrial dynamics regulate melanogenesis
      by modulating the ROS-ERK signaling pathway. Genetic and chemical inhibition of
      Drp1, a mitochondrial fission protein, increased melanin production and
      mitochondrial elongation in melanocytes and melanoma cells. In contrast, down
      regulation of OPA1, a mitochondria fusion regulator, suppressed melanogensis but
      induced massive mitochondrial fragmentation in hyperpigmented cells.
      Consistently, treatment with CCCP, a mitochondrial fission chemical inducer, also
      efficiently repressed melanogenesis. Furthermore, we found that ROS production
      and ERK phosphorylation were increased in cells with fragmented mitochondria. And
      inhibition of ROS or ERK suppressed the antimelanogenic effect of mitochondrial
      fission in alpha-MSH-treated cells. In addition, the activation of ROS-ERK
      pathway by mitochondrial fission induced phosphorylation of serine73 on MITF
      accelerating its proteasomal degradation. In conclusion, mitochondrial dynamics
      may regulate melanogenesis by modulating ROS-ERK signaling pathway. 

PMID- 25065406
TI  - Hemolysis as a rare but potentially life-threatening complication of
      hemodialysis: a case report.
AB  - BACKGROUND: The burden of end-stage renal disease (ESRD) in the United States has
      increased dramatically over the past 30 years with almost 613,000 patients
      receiving renal replacement therapy in 2011. That same year, more than 112,000
      new patients initiated dialysis with 92% of them receiving hemodialysis (HD).
      These patients experience significant morbidity and mortality with very frequent
      emergency room visits. Acute hemolysis associated with HD is a rare complication;
      however, if it's not recognized early and managed adequately, it can be
      associated with life-threatening complications such as hyperkalemia and even
      myocardial infarction. CASE PRESENTATION: 66-year-old African-American female
      with a history of ESRD secondary to hypertension developed a blood infiltration
      on the arterial side of her arteriovenous fistula followed by sudden onset of
      diffuse abdominal pain with nausea and vomiting during her regular HD treatment.
      She was referred to the emergency department where she was found to have
      shortness of breath with improved gastrointestinal symptoms. Her initial work-up
      revealed a severe anemia with a hematocrit of 10%. Further work-up revealed
      massive hemolysis, likely mechanical in nature and believed to be induced by
      malpositioning of her HD needle in the fistula. Her hospital course was
      complicated by rhabdomyolysis and acute myocardial infarction thought to be
      secondary to supply-demand ischemia in the setting of her profound anemia. Within
      a week, she eventually had a full recovery. CONCLUSION: It is extremely important
      for physicians and particularly emergency department physicians to be aware of
      this potentially life-threatening complication of HD and have a high index of
      suspicion in the setting of acute anemia with hemolysis in this population.

PMID- 25065407
TI  - How much do we know about schizophrenia and how well do we know it? Evidence from
      the Schizophrenia Library.
AB  - BACKGROUND: True findings about schizophrenia remain elusive; many findings are
      not replicated and conflicting results are common. Well-conducted systematic
      reviews have the ability to make robust, generalizable conclusions, with good
      meta-analyses potentially providing the closest estimate of the true effect size.
      In this paper, we undertake a systematic approach to synthesising the available
      evidence from well-conducted systematic reviews on schizophrenia. METHOD: Reviews
      were identified by searching Medline, EMBASE, CINAHL, Current Contents and
      PsycINFO. The decision to include or exclude reviews, data extraction and quality
      assessments were conducted in duplicate. Evidence was graded as high quality if
      reviews contained large samples and robust results; and as moderate quality if
      reviews contained imprecision, inconsistency, smaller samples or study designs
      that may be prone to bias. RESULTS: High- and moderate-quality evidence shows
      that numerous psychosocial and biomedical treatments are effective. Patients have
      relatively poor cognitive functioning, and subtle, but diverse, structural brain
      alterations, altered electrophysiological functioning and sleep patterns, minor
      physical anomalies, neurological soft signs, and sensory alterations. There are
      markers of infection, inflammation or altered immunological parameters; and there
      is increased mortality from a range of causes. Risk for schizophrenia is
      increased with cannabis use, pregnancy and birth complications, prenatal exposure
      to Toxoplasma gondii, childhood central nervous system viral infections,
      childhood adversities, urbanicity and immigration (first and second generation),
      particularly in certain ethnic groups. Developmental motor delays and lower
      intelligence quotient in childhood and adolescence are apparent. CONCLUSIONS: We
      conclude that while our knowledge of schizophrenia is very substantial, our
      understanding of it remains limited.

PMID- 25065408
TI  - The C-terminal module IV of connective tissue growth factor, through EGFR/Nox1
      signaling, activates the NF-kappaB pathway and proinflammatory factors in
      vascular smooth muscle cells.
AB  - AIMS: Connective tissue growth factor (CTGF/CCN2) is a developmental gene
      upregulated in pathological conditions, including cardiovascular diseases, whose
      product is a matricellular protein that can be degraded to biologically active
      fragments. Among them, the C-terminal module IV [CCN2(IV)] regulates many
      cellular functions, but there are no data about redox process. Therefore, we
      investigated whether CCN2(IV) through redox signaling regulates vascular
      responses. RESULTS: CCN2(IV) increased superoxide anion (O2(*-)) production in
      murine aorta (ex vivo and in vivo) and in cultured vascular smooth muscle cells
      (VSMCs). In isolated murine aorta, CCN2(IV), via O2(*-), increased phenylephrine
      induced vascular contraction. CCN2(IV) in vivo regulated several redox-related
      processes in mice aorta, including increased nonphagocytic NAD(P)H oxidases
      (Nox)1 activity, protein nitrosylation, endothelial dysfunction, and activation
      of the nuclear factor-kappaB (NF-kappaB) pathway and its related proinflammatory
      factors. The role of Nox1 in CCN2(IV)-mediated vascular responses in vivo was
      investigated by gene silencing. The administration of a Nox1 morpholino
      diminished aortic O2(*-) production, endothelial dysfunction, NF-kappaB
      activation, and overexpression of proinflammatory genes in CCN2(IV)-injected
      mice. The link CCN2(IV)/Nox1/NF-kappaB/inflammation was confirmed in cultured
      VSMCs. Epidermal growth factor receptor (EGFR) is a known CCN2 receptor. In
      VSMCs, CCN2(IV) activates EGFR signaling. Moreover, EGFR kinase inhibition
      blocked vascular responses in CCN2(IV)-injected mice. INNOVATION AND CONCLUSION:
      CCN2(IV) is a novel prooxidant factor that in VSMCs induces O2(*-) production via
      EGFR/Nox1 activation. Our in vivo data demonstrate that CCN2(IV) through
      EGFR/Nox1 signaling pathway induces endothelial dysfunction and activation of the
      NF-kappaB inflammatory pathway. Therefore, CCN2(IV) could be considered a
      potential therapeutic target for redox-related cardiovascular diseases.

PMID- 25065409
TI  - Empirical evidence for discrete neurocognitive subgroups in bipolar disorder:
      clinical implications.
AB  - BACKGROUND: Recent data suggest trait-like neurocognitive impairments in bipolar
      disorder (BPD), with deficits about 1 s.d. below average, less severe than
      deficits noted in schizophrenia. The frequency of significant impairment in BPD
      is approximately 60%, with 40% of patients characterized as cognitively spared.
      This contrasts with a more homogeneous presentation in schizophrenia. It is not
      understood why some BPD patients develop deficits while others do not. METHOD: A
      total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery
      and data were entered into hierarchical cluster analyses to: (1) determine the
      optimal number of clusters (subgroups) that fit the sample; and (2) assign
      subjects to a specific cluster based on individual profiles. We then compared
      subgroups on several clinical factors and real-world community functioning.
      RESULTS: Three distinct neurocognitive subgroups were found: (1) an intact group
      with performance comparable with healthy controls on all domains but with
      superior social cognition; (2) a selective impairment group with moderate
      deficits on processing speed, attention, verbal learning and social cognition and
      normal functioning in other domains; and (3) a global impairment group with
      severe deficits across all cognitive domains comparable with deficits in
      schizophrenia. CONCLUSIONS: These results suggest the presence of multiple
      cognitive subgroups in BPD with unique profiles and begin to address the
      relationships between these subgroups, several clinical factors and functional
      outcome. Next steps will include using these data to help guide future efforts to
      target these disabling symptoms with treatment.

PMID- 25065410
TI  - Psychotic experiences and psychological distress predict contemporaneous and
      future non-suicidal self-injury and suicide attempts in a sample of Australian
      school-based adolescents.
AB  - BACKGROUND: Recent cross-sectional studies have shown psychotic experiences (PEs)
      are associated with suicidal ideation and behaviours. We aimed to examine
      associations between psychotic experiences (including persistent PE), and
      contemporaneous and incident non-suicidal self-injury (NSSI) and suicide
      attempts. METHOD: Participants were from an Australian longitudinal cohort of
      1896 adolescents (12-17 years). NSSI and suicide attempts were measured using the
      Self-Harm Behaviour Questionnaire. Items from the Diagnostic Interview Schedule
      for Children were used to assess psychotic experiences, and the General Health
      Questionnaire-12 measured psychological distress. RESULTS: Adolescents both
      psychologically distressed and endorsing psychotic experiences had increased odds
      of contemporaneous and incident NSSI and attempted suicide. Psychotic experiences
      alone did not predict future risk. Persistent psychotic experiences were
      associated with increased risk of NSSI and suicide attempts. CONCLUSIONS:
      Psychological distress with accompanying psychotic experiences and persistent
      psychotic experiences are important predictors of NSSI and suicide attempts.
      Screening these phenotypes in adolescents will assist in discerning those
      adolescents most at risk, providing opportunities for targeted suicide prevention
      strategies.

PMID- 25065411
TI  - Danger and loss events and the incidence of anxiety and depressive disorders: a
      prospective-longitudinal community study of adolescents and young adults.
AB  - BACKGROUND: There are inconclusive findings regarding whether danger and loss
      events differentially predict the onset of anxiety and depression. METHOD: A
      community sample of adolescents and young adults (n = 2304, age 14-24 years at
      baseline) was prospectively followed up in up to four assessments over 10 years.
      Incident anxiety and depressive disorders were assessed at each wave using the
      DSM-IV/M-CIDI. Life events (including danger, loss and respectively mixed events)
      were assessed at baseline using the Munich Event List (MEL). Logistic regressions
      were used to reveal associations between event types at baseline and incident
      disorders at follow-up. RESULTS: Loss events merely predicted incident 'pure'
      depression [odds ratio (OR) 2.4 per standard deviation, 95% confidence interval
      (CI) 1.5-3.9, p < 0.001] whereas danger events predicted incident 'pure' anxiety
      (OR 2.3, 95% CI 1.1-4.6, p = 0.023) and 'pure' depression (OR 2.5, 95% CI 1.7
      3.5, p < 0.001). Mixed events predicted incident 'pure' anxiety (OR 2.9, 95% CI
      1.5-5.7, p = 0.002), 'pure' depression (OR 2.4, 95% CI 1.6-3.4, p < 0.001) and
      their co-morbidity (OR 3.6, 95% CI 1.8-7.0, p < 0.001). CONCLUSIONS: Our results
      provide further evidence for differential effects of danger, loss and
      respectively mixed events on incident anxiety, depression and their co-morbidity.
      Since most loss events referred to death/separation from significant others,
      particularly interpersonal loss appears to be highly specific in predicting
      depression.

PMID- 25065412
TI  - Detecting objective and subjective cognitive effects of electroconvulsive
      therapy: intensity, duration and test utility in a large clinical sample.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for
      depression but the extent and persistence of cognitive side-effects remain
      uncertain. It has been reported that there is little evidence that impairments
      last longer than up to 15 days post-ECT. However, relatively few studies have
      followed patients for even as long as 1 month post-ECT. Here we report results
      from a brief cognitive battery given prior to ECT and repeated five times up to 6
      months post-ECT. METHOD: In a retrospective case-note study of routinely
      collected clinical data 126 patients treated with ECT completed two
      neuropsychological tests [Cambridge Neuropsychological Test Automated Battery
      (CANTAB) spatial recognition memory (SRM) and Mini Mental State Examination
      (MMSE)] and two subjective reports of memory function, prior to ECT. Patients
      were reassessed following ECT and at 1, 3 and 6 months post-ECT although not all
      patients completed all assessments. RESULTS: Performance relative to pre-ECT
      baseline was significantly poorer at each post-ECT assessment up to 3 months post
      ECT using the CANTAB SRM, but was improved at 6 months. Conversely, MMSE score
      showed improvements relative to baseline from 1 month post-ECT. Mood and
      subjective memory scores improved following ECT and were correlated with one
      another, but not with either neuropsychological measure. CONCLUSIONS: The CANTAB
      SRM task revealed reversible cognitive deficiencies relative to a pre-ECT
      baseline for at least 3 months following ECT, while MMSE score and patients'
      subjective reports showed only improvement. Visuospatial memory scores eventually
      exceeded baseline 6 months post-ECT.

PMID- 25065413
TI  - The relation between treatment and prognosis of childhood membranoproliferative
      glomerulonephritis.
AB  - BACKGROUND: The prognostic factors, the outcome and the most favorable treatment
      regimen are not entirely known for children with membranoproliferative
      glomerulonephritis (MPGN). MPGN is a rarely observed disease more prevalent in
      adolescents, so we aimed to review the clinical and histological properties,
      treatments and the outcome of our patients who were diagnosed as MPGN. METHODS:
      Fifty-one children - diagnosed with MPGN - were selected from biopsy records in
      Dr. Sami Ulus Maternity and Children's Hospital Pediatric Nephrology Department
      from January 1999 to January 2011. A retrospective analysis was made of 33
      regularly followed children. RESULTS: Thirty-three patients were identified, 13
      female and 20 male. Their age groups at presentation ranged from 4 to 15 years.
      The following duration was 26-144 months (mean 74). Following the initial
      treatment, 20 (60%) patients achieved complete remission. Six patients with
      nephrotic syndrome and one with non-nephrotic proteinuria showed partial
      remission. The condition of one patient with nephrotic syndrome was unchanged
      with the persisting symptoms. The one patient with nephrotic syndrome and four
      others with non-nephrotic proteinuria did not respond to initial treatment as
      their renal functions decreased gradually. CONCLUSION: We concluded that only
      degree of tubulointerstitial damage on the initial biopsy is determinative for
      prognosis of childhood MPGN. If the patient receives high doses of steroid
      therapy in the early stages, their treatment is more likely to be successful. The
      effect of immunosuppressive treatment on MPGN is not clear.

PMID- 25065414
TI  - Process evaluation outcomes from a global child obesity prevention intervention.
AB  - BACKGROUND: While it is acknowledged that child obesity interventions should
      cover multiple ecological levels (downstream, midstream and upstream) to maximize
      their effectiveness, there is a lack of evaluation data to guide the development
      and implementation of such efforts. To commence addressing this knowledge gap,
      the present study provides process evaluation data relating to the experiences of
      groups implementing the EPODE approach to child obesity prevention in various
      locations around the world. The aim of this exploratory study was to investigate
      the barriers and facilitators to program implementation in program sites around
      the world to assist in developing strategies to enhance program outcomes.
      METHODS: An online survey that included open-ended questions was distributed to
      the 25 EPODE programs in operation at the time of the survey (May 2012). The
      survey items asked respondents to comment on those aspects of program
      implementation that they found challenging and to suggest areas for future
      improvement. Eighteen programs representing 14 countries responded to the request
      to participate in the survey, yielding a 72% response rate. The responses were
      analyzed via the constant comparative method using NVivo qualitative data
      analysis software. RESULTS: The main concerns of the various EPODE programs were
      their ability to secure ongoing funding and their access to evidence-based
      intervention methods and policy advice relating to relationships with third
      parties. These issues were in turn impacted by other factors, including (i)
      access to user-friendly information relating to the range of intervention
      strategies available and appropriate evaluation measures; (ii) assistance with
      building and maintaining stakeholder relationships; and (iii) assurance of the
      quality, independence, and transparency of policies and practices. CONCLUSIONS:
      The findings are facilitating the ongoing refinement of the EPODE approach. In
      particular, standardized and tailored information packages are being made
      available to advise program members of (i) the various evaluation methods and
      tools at their disposal and (ii) methods of acquiring private partner support.
      Overall, the study results relating to the types of issues encountered by program
      members are likely to be useful in guiding the future design and implementation
      of multi-level initiatives seeking to address other complex and intractable
      health-related problems.

PMID- 25065415
TI  - Highly transparent Au-coated Ag nanowire transparent electrode with reduction in
      haze.
AB  - Ag nanowire transparent electrode has excellent transmittance and sheet
      resistance, yet its optical haze still needs to be improved in order for it to be
      suitable for display applications. Ag nanowires are known to have high haze
      because of the geometry of the nanowire and the high light scattering
      characteristic of the Ag. In this study, a Au-coated Ag nanowire structure was
      proposed to reduce the haze, where a thin layer of Au was coated on the surface
      of the Ag nanowires using a mild [Au(en)2]Cl3 galvanic displacement reaction. The
      mild galvanic exchange allowed for a thin layer of Au coating on the Ag nanowires
      with minimal truncation of the nanowire, where the average length and the
      diameter were 13.0 MUm and 60 nm, respectively. The Au-coated Ag nanowires were
      suspended in methanol and then electrostatically sprayed on a flexible
      polycarbonate substrate that revealed a clear reduction in haze with a 2-4%
      increase in total transmittance, sheet resistance ranges of 80-90%, and 8.8-36.8
      Ohm/sq. Finite difference time domain simulations were conducted for Au-coated Ag
      nanowires that indicated a significant reduction in the average scattering from 1
      to 0.69 for Au layer thicknesses of 0-10 nm. 

PMID- 25065416
TI  - Laser assisted lipolysis for neck and submental remodeling in Rohrich type I to
      III aging neck: a prospective study in 30 patients.
AB  - BACKGROUND: Since the first studies by Apfelberg in 1994 and the mathematical
      model by Mordon in 2004, laser lipolysis (LAL) has been on the rise. Laser
      lipolysis has the advantages of reduced operator fatigue, excellent patient
      tolerance, quick recovery time, as well as the additional benefit of dermal
      tightening. This article reports our experience with laser-assisted lipolysis
      (LAL) in submental and neck remodelling. METHODS: Between June 2010 and January
      2013, a prospective study was performed on 30 patients treated for Rohrich type I
      to III aging neck, with LAL. The laser used in this study was a 980 nm diode
      laser (Quanta system, spa model D-plus, Solbate Olona (VA), Italy). Laser energy
      was transmitted through a 600 MUm optical fiber and delivered in a continuous
      mode 15 W power. Previous mathematical modelling suggested that 0.1 kJ was
      required in order to destroy 1 ml of fat. Patients were asked to fill out a
      satisfaction questionnaire. The cervicomental angle was measured 6 months post
      operatively and compared with the preoperative values. RESULTS: Other than three
      patients who developed mild hyperpigmentation that disappeared after 4 months,
      there were no complications in the series. Pain during the anaesthesia and
      discomfort after the procedure were minimal. The time taken to return to normal
      activities was 3.2 +/- 1 days. All patients would strongly recommend this
      treatment. Overall satisfaction was high with both patients and investigators and
      was validated by decrease in cervicomental angle demonstrating a systematic
      decrease in fat thickness and improved skin tightening. CONCLUSION: LAL is a safe
      and reproducible technique for remodeling in Rohrich type I to III aging neck.
      The procedure allows for a reduction in the amount of adipose deposits while
      providing concurrent skin contraction.

PMID- 25065417
TI  - Repeated salicylic acid peels for the treatment of hyperplastic sebaceous glands
      in hypohidrotic ectodermal dysplasia.
AB  - Hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) is the most
      common type of ectodermal dysplasia. Hypertrophic sebaceous glands (HSGs) are
      rarely present but they cause an aesthetic problem. We report a case of a patient
      suffering from hypohidrotic ectodermal dysplasia, treated with salicylic acid
      peels for the hyperplastic sebaceous glands.

PMID- 25065419
TI  - Obesity does not increase complication rate of percutaneous epicardial access.
AB  - INTRODUCTION: Percutaneous epicardial access for ablative therapies is an
      increasingly common technique utilized for refractory ventricular arrhythmias.
      There are, however few known data on obesity and complication rates associated
      with this procedure. METHODS AND RESULTS: We retrospectively reviewed the charts
      of subjects undergoing epicardial access at Mayo Clinic between January 2004 and
      June 2013. Baseline clinical and echocardiographic data were collected for each
      subject, who was then classified into body mass index (BMI) categories as
      underweight, normal weight, overweight, and obese based on a BMI of <18.5, 18.5
      24.99, 25-29.99, and >=30, respectively. Events and complications were recorded,
      and procedural and clinical success rates were determined. There was no
      statistically significant difference in access approach, procedural or clinical
      outcomes, or complications among the BMI categories. Note that 95.1%, 91.7%, and
      93.1% derived procedural success among the normal weight, overweight, and obese
      categories, respectively (P value = 0.81). Similarly, there was no difference in
      clinical outcomes with success rates of 68.3%, 66.7%, and 75.9% between the
      respective groups (P value = 0.54). At 5 years, there was a trend toward
      increased mortality among obese individuals (28.8%) compared to normal weight
      (8.8%) and overweight (9.8%) patients (P value = 0.139). CONCLUSION: Percutaneous
      epicardial access, mapping, and ablation can be performed in obese individuals
      with similar outcomes to those of lower weight category. Obesity should not
      preclude the use of percutaneous epicardial access when clinically indicated.

PMID- 25065421
TI  - A promising monolayer membrane for oxygen separation from harmful gases: nitrogen
      substituted polyphenylene.
AB  - We theoretically demonstrate that N-substitutional doping dramatically reduces
      the diffusion barrier for oxygen passing through the pores of polyphenylene,
      leading to a massive enhancement in O2 selectivity over various harmful gases
      with excellent permeance at appropriate temperatures for O2 across an N-doped
      polyphenylene in a unit cell. 

PMID- 25065423
TI  - Patient safety: the elephant in the room.

PMID- 25065420
TI  - Examining potential school contextual influences on gambling among high school
      youth.
AB  - BACKGROUND AND OBJECTIVES: Gambling is an increasing concern among adolescence,
      yet there has been limited investigation into school-level factors that may
      increase the risk for gambling. The current study examined the relationship
      between substance use and gambling, and explored the influence of school context
      on adolescent gambling. METHODS: Data come from 25,456 students in 58 high
      schools participating in the Maryland Safe and Supportive Schools Initiative.
      Youth-reports of socio-demographics, lifetime gambling, and past-month substance
      use (ie, alcohol, cigarette, marijuana, non-medical prescription drug) were
      collected. School-level characteristics were student suspension rate, student
      mobility, percentage of students receiving free/reduce-priced meals, percentage
      of African American students, urbanicity, gambling prevalence, gambling problem
      prevalence, and substance use prevalence. Weighted multilevel analyses were
      conducted. RESULTS: One-third (n = 8,318) reported lifetime gambling, and 10% (n
      = 2,580) of the full sample, or 31% of the gamblers, experienced gambling
      problems. Being male and alcohol, marijuana, and non-medical prescription drug
      use were associated with twice the odds of gambling. Among gamblers, being male,
      African American, and cigarette, marijuana, and non-medical prescription drug use
      were associated with higher odds of gambling problems. The school-level factors
      of suspension rate and percentage of African American had minimal, inverse
      associations with gambling; however, none were related to gambling problems.
      CONCLUSIONS: Multilevel results indicated that adolescents that are male and use
      substances are more likely to gamble and have gambling problems. SCIENTIFIC
      SIGNIFICANCE: The findings indicate a need for prevention programs targeting
      risky behaviors to also target gambling as such behaviors often co-occur among
      adolescents.

PMID- 25065424
TI  - A comparative evaluation of analgo-sedative effects of oral dexmedetomidine and
      ketamine: a triple-blind, randomized study.
AB  - BACKGROUND: Use of sedative agents for difficult to manage children during dental
      procedures has been indicated for years, but neither the agent nor the route has
      been found to be ideal. OBJECTIVES: The aim of the study was to evaluate and
      compare the efficacy and safety of oral dexmedetomidine (D) and ketamine (K) in
      producing moderate sedation among uncooperative pediatric dental patients.
      METHODS: This prospective, triple-blind, randomized comparative study included
      112 ASA grade I children of both sexes aged 3-10 years, who satisfied all the
      inclusion criteria. They were randomly divided into four groups and ketamine 8
      mg.kg(-1) (K) or dexmedetomidine 3 MUg.kg(-1) (D1), 4 MUg.kg(-1) (D2) and 5
      MUg.kg(-1) (D3) were given orally. Similar dental procedures were performed in
      these patients, and effects of these drugs were assessed in terms of changes in
      vital signs, onset and duration of sedation, analgesia, and amnesia. Secondary
      outcomes such as level of sedation, behavior, adverse effects, and overall
      success were also measured. RESULTS: The onset of sedation was significantly
      rapid with K and D3 as compared to D1 and D2. Recovery from sedation was fastest
      in group D1. Intra- and postoperative analgesia and anterograde amnesia were
      highest with K and least with D1, while D3 produced analgesia comparable to K. In
      K treated group, vomiting was observed in five patients and two patients
      exhibited emergence phenomenon. Overall, highest success rate was observed in D3
      group. CONCLUSIONS: Given by oral route, the novel sedative dexmedetomidine
      provides dose-dependent effective analgo-sedation, comparable to ketamine, with
      less adverse effects.

PMID- 25065425
TI  - Evaluating multispecies landscape connectivity in a threatened tropical mammal
      community.
AB  - Habitat corridors are important tools for maintaining connectivity in
      increasingly fragmented landscapes, but generally they have been considered in
      single-species approaches. Corridors intended to facilitate the movement of
      multiple species could increase persistence of entire communities, but at the
      likely cost of being less efficient for any given species than a corridor
      intended specifically for that species. There have been few tests of the trade
      offs between single- and multispecies corridor approaches. We assessed single
      species and multispecies habitat corridors for 5 threatened mammal species in
      tropical forests of Borneo. We generated maps of the cost of movement across the
      landscape for each species based on the species' local abundance as estimated
      through hierarchical modeling of camera-trap data with biophysical and
      anthropogenic covariates. Elevation influenced local abundance of banded civets
      (Hemigalus derbyanus) and sun bears (Helarctos malayanus). Increased road density
      was associated with lower local abundance of Sunda clouded leopards (Neofelis
      diardi) and higher local abundance of sambar deer (Rusa unicolor). Pig-tailed
      macaque (Macaca nemestrina) local abundance was lower in recently logged areas.
      An all-species-combined connectivity scenario with least-cost paths and 1 km
      buffers generated total movement costs that were 27% and 23% higher for banded
      civets and clouded leopards, respectively, than the connectivity scenarios for
      those species individually. A carnivore multispecies connectivity scenario,
      however, increased movement cost by 2% for banded civets and clouded leopards.
      Likewise, an herbivore multispecies scenario provided more effective connectivity
      than the all-species-combined scenario for sambar and macaques. We suggest that
      multispecies habitat connectivity plans be tailored to groups of ecologically
      similar, disturbance-sensitive species to maximize their effectiveness.

PMID- 25065426
TI  - Trauma verification: for the trauma centre or for the trauma system?

PMID- 25065427
TI  - Enhanced Recovery After Surgery and laparoscopic colorectal surgery: where to
      now?

PMID- 25065429
TI  - Barrett's oesophagus, cancer and antireflux surgery.

PMID- 25065430
TI  - Response to Re: Current Australian practice in the diagnosis and management of
      Barrett's oesophagus.

PMID- 25065431
TI  - A complex Amyand's hernia: strangulated hernia with incarceration of small bowel
      and vermiform appendix.

PMID- 25065432
TI  - Piezotronic interface engineering on ZnO/Au-based Schottky junction for enhanced
      photoresponse of a flexible self-powered UV detector.
AB  - Exploiting piezoelectric effect to engineer material interface has been confirmed
      as a promising way to optimize the performance of optoelectronic devices. Here,
      by using this effect, we have greatly improved the photoresponse of the
      fabricated ZnO/Au Schottky junction based self-powered UV detector. A 440%
      augment of photocurrent, together with 5* increased sensitivity, was obtained
      when the device was subjected to a 0.580% tensile strain. The enhancement can be
      attributed to the facility separation and extraction of photoexcites due to the
      formation of the stronger and expanding built-in field, which is a result of
      charge redistribution induced by piezoelectric polarization at the ZnO/Au
      interface. This study not only can strengthen the understanding of piezoelectric
      effects on energy devices but also can be extended to boost performances of
      optoelectronic devices made of piezoelectric semiconductor materials. 

PMID- 25065433
TI  - Clearing the smoke.

PMID- 25065434
TI  - Something wicked this way comes: huntingtin.

PMID- 25065435
TI  - A selector orchestrates cortical function.

PMID- 25065436
TI  - Getting it through your thick skull.

PMID- 25065437
TI  - Sleep replay meets brain-machine interface.

PMID- 25065438
TI  - A common affective code.

PMID- 25065439
TI  - Direct and indirect pathways of basal ganglia: a critical reappraisal.
AB  - The basal ganglia are subcortical nuclei controlling voluntary actions and have
      been implicated in Parkinson's disease (PD). The prevailing model of basal
      ganglia function states that two circuits, the direct and indirect pathways,
      originate from distinct populations of striatal medium spiny neurons (MSNs) and
      project to different output structures. These circuits are believed to have
      opposite effects on movement. Specifically, the activity of direct pathway MSNs
      is postulated to promote movement, whereas the activation of indirect pathway
      MSNs is hypothesized to inhibit it. Recent findings have revealed that this model
      might not fully account for the concurrent activation of both pathways during
      movement. Accordingly, we propose a model in which intrastriatal connections are
      critical and the two pathways are structurally and functionally intertwined.
      Thus, all MSNs might either facilitate or inhibit movement depending on the form
      of synaptic plasticity expressed at a certain moment. In PD, alterations of
      dopamine-dependent synaptic plasticity could alter this coordinated activity. 

PMID- 25065441
TI  - Autoantibodies against TIF-1-gamma and CADM-140 in Spanish patients with
      clinically amyopathic dermatomyositis (CADM): clinical significance and
      diagnostic utility.
AB  - BACKGROUND: Patients with clinically amyopathic dermatomyositis (CADM) appear to
      be at risk for developing cancer and interstitial lung diseases, but population
      data to confirm this hypothesis are limited. Moreover, CADM presents cutaneous
      and histological findings that may overlap with subacute cutaneous lupus
      erythematosus (SCLE). OBJECTIVES: To determine the association between myositis
      specific autoantibodies, myositis-associated autoantibodies and CADM in Spanish
      patients. In addition, to study the usefulness of these autoantibodies in the
      differential diagnosis between CADM and SCLE. METHODS: Serum samples were tested
      for myositis-specific autoantibodies and myositis-associated autoantibodies
      through immunoprecipitation and other standardized methods. RESULTS: Anti-CADM
      p140 and anti-p155 antibodies were the only myositis-specific autoantibodies
      found and were associated with interstitial lung diseases and cancer
      respectively. No myositis-associated autoantibodies were found in CADM. Moreover,
      clinical subsets and proportions seemed to differ from Asian cohorts, where anti
      CADM-p140 is considered a CADM hallmark antibody and a risk factor for the
      development of interstitial lung disease. Interestingly, anti-SSA was highly
      associated with SCLE, whereas no myositis-specific autoantibodies were found in
      this entity. LIMITATIONS OF THE STUDY: Association between CADM and myositis
      specific autoantibodies and differences between CADM and SCLE were tested on a
      relatively small cohort of patients. CONCLUSION: There is an association between
      cancer-associated myositis and interstitial lung diseases and their hallmark
      autoantibodies in our cohort. In addition, the combined determination of myositis
      specific autoantibodies and SSA autoantibodies may help to accurately
      discriminate SCLE from CADM.

PMID- 25065440
TI  - Dynamic circuit motifs underlying rhythmic gain control, gating and integration.
AB  - Brain circuitry processes information by rapidly and selectively engaging
      functional neuronal networks. The dynamic formation of networks is often evident
      in rhythmically synchronized neuronal activity and tightly correlates with
      perceptual, cognitive and motor performances. But how synchronized neuronal
      activity contributes to network formation and how it relates to the computation
      of behaviorally relevant information has remained difficult to discern. Here we
      structure recent empirical advances that link synchronized activity to the
      activation of so-called dynamic circuit motifs. These motifs explicitly relate
      (1) synaptic and cellular properties of circuits to (2) identified timescales of
      rhythmic activation and to (3) canonical circuit computations implemented by
      rhythmically synchronized circuits. We survey the ubiquitous evidence of specific
      cell and circuit properties underlying synchronized activity across theta, alpha,
      beta and gamma frequency bands and show that their activation likely implements
      gain control, context-dependent gating and state-specific integration of synaptic
      inputs. This evidence gives rise to the dynamic circuit motifs hypothesis of
      synchronized activation states, with its core assertion that activation states
      are linked to uniquely identifiable local circuit structures that are recruited
      during the formation of functional networks to perform specific computational
      operations. 

PMID- 25065442
TI  - Antidepressants, autonomic function and mortality in patients with coronary heart
      disease: data from the Heart and Soul Study.
AB  - BACKGROUND: Antidepressants reduce depressive symptoms in patients with coronary
      heart disease, but they may be associated with increased mortality. This study
      aimed to examine whether the use of tricyclic antidepressants (TCA) or selective
      serotonin reuptake inhibitors (SSRI) is associated with mortality in patients
      with coronary heart disease, and to determine whether this association is
      mediated by autonomic function. METHOD: A total of 956 patients with coronary
      heart disease were followed for a mean duration of 7.2 years. Autonomic function
      was assessed as heart rate variability, and plasma and 24-h urinary
      norepinephrine. RESULTS: Of 956 patients, 44 (4.6%) used TCA, 89 (9.3%) used
      SSRI, and 823 (86.1%) did not use antidepressants. At baseline, TCA users
      exhibited lower heart rate variability and higher norepinephrine levels compared
      with SSRI users and antidepressant non-users. At the end of the observational
      period, 52.3% of the TCA users had died compared with 38.2% in the SSRI group and
      37.3% in the control group. The adjusted hazard ratio (HR) for TCA use compared
      with non-use was 1.74 [95% confidence interval (CI) 1.12-2.69, p = 0.01]. Further
      adjustment for measures of autonomic function reduced the association between TCA
      use and mortality (HR = 1.27, 95% CI 0.67-2.43, p = 0.47). SSRI use was not
      associated with mortality (HR = 1.15, 95% CI 0.81-1.64, p = 0.44). CONCLUSIONS:
      The use of TCA was associated with increased mortality. This association was at
      least partially mediated by differences in autonomic function. Our findings
      suggest that TCA should be avoided in patients with coronary heart disease.

PMID- 25065443
TI  - Resistance mechanisms of cancer cells to the novel vacuolar H(+)-ATPase inhibitor
      archazolid B.
AB  - Resistance of cancer cells towards chemotherapy is the major cause of therapy
      failure. Hence, the evaluation of cellular defense mechanisms is essential in the
      establishment of new chemotherapeutics. Archazolid B, a novel vacuolar H(+)
      ATPase inhibitor, displayed cytotoxicity in the low nanomolar range on a panel of
      different tumor cell lines. First, we investigated tumor-specific cytotoxicity of
      archazolid B by comparing cancer to non-cancer cells. Breast, liver and colon
      cancer cells displayed higher drug sensitivity than corresponding non-tumorous
      cells, whereas leukemia cell lines were as sensitive as peripheral mononuclear
      blood cells. Investigating classical drug resistance mechanisms, archazolid B was
      identified as a possible substrate of the ABC transporters ABCB1 (P-glycoprotein)
      and ABCG2 (BCRP), whereas collateral sensitivity was observed in ABCB5-expressing
      cells. Our results pointed to a possible binding competition of archazolid B with
      verapamil on P-glycoprotein. However, archazolid B did not reverse resistance
      towards doxorubicin indicating that it might be a substrate but not an inhibitor
      of P-glycoprotein mediated transport. Furthermore, the cytotoxicity of archazolid
      B was independent of the p53 status of the cell. Mechanisms of aquired resistance
      were investigated establishing an archazolid B-resistant MCF-7 cell line.
      Interestingly, drug resistance was not conferred by aberrant expression or DNA
      mutations of the gene encoding vacuolar H(+)-ATPase subunit c, the direct target
      of archazolids. Instead, long-term treatment with archazolid B led to a slight
      overexpression of ABCB1 and a significant overexpression of the epidermal growth
      factor receptor and reduced cell growth, all of which can be assumed to
      contribute to archazolid B resistance.

PMID- 25065444
TI  - Localized juvenile spongiotic gingival hyperplasia featuring unusual p16INK4A
      labeling and negative human papillomavirus status by polymerase chain reaction.
AB  - BACKGROUND: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a
      distinct type of gingival hyperplastic lesion with specific clinicopathologic
      features. Evaluation of the morphological characteristics of LJSGH indicates the
      potential role of human papillomavirus (HPV) infection as an underlying
      etiopathogenetic mechanism. METHODS: All cases of LJSGH from 2008 to present were
      retrieved. Clinical and demographic data were collected. HPV status was
      investigated by p16INK4A immunohistochemistry and HPV-Polymerase chain reaction
      (PCR). RESULTS: Twenty-one cases of LJSGH were identified, 14 (66.7%) affecting
      males and seven (33.3%) females (M:F = 2:1, age range: 8-36, mean: 13 years). All
      lesions were well-demarcated, exophytic, erythematous, and hemorrhagic with
      granular or slightly papillary surface. Preponderance for the maxillary gingiva
      (19, 90.5%) was observed. Two (9.5%) patients presented with recurrence 20 and 21
      months after excision (mean follow-up: 18.7 months). Histopathologically, all
      LJSGH lesions featured epithelial hyperplasia with intense neutrophilic
      exocytosis and spongiosis. All cases demonstrated positivity for p16INK4A with
      the majority of specimens (47.6%) intensely decorated in >50% of the overlying
      epithelium with focal immunostaining observed in 47.6% and diffuse in 52.4%.
      Thirteen cases (61.9%) were negative for HPV DNA by PCR, while two (9.5%) were
      suspicious for the presence of low levels of HPV DNA but definitive genotyping
      was not possible. One case (4.8%) displayed positivity for HPV-31. The remaining
      five cases failed the PCR reaction. CONCLUSIONS: Human papillomavirus does not
      participate in the pathogenesis of LJSGH. P16INK4A expression in the absence of
      detectable HPV DNA can likely be attributed to the intense inflammation
      associated with LJSGH.

PMID- 25065445
TI  - Alterations in white matter micro-integrity of the superior longitudinal
      fasciculus and anterior thalamic radiation of young adult patients with
      depression.
AB  - BACKGROUND: This study surveyed the characteristics of white matter (WM) micro
      integrity in patients who were diagnosed with major depressive disorder (MDD)
      without co-morbidities. METHOD: A total of 44 patients with MDD and 27 normal
      controls were enrolled in our study. Diffusion tensor imaging images of patients
      and controls were pre-processed and analysed to estimate differences in WM micro
      integrity between patients and controls by performing comparisons of the values
      obtained from fractional anisotropy (FA). FA outputs of patients and controls
      were compared by a non-parametric permutation-based method with global brain
      volume, age and gender as covariates. In addition, the between-group differences
      of radial diffusivity (RD) and axial diffusivity (AD) were assessed to explain
      the alterations in FA values. Correlations between clinical variables (such as
      depression severity, anxiety severity, illness duration) and FA values were also
      estimated in each group and across both groups. RESULTS: The patients with MDD
      had significantly lower FA values than the controls, for the left superior
      longitudinal fasciculus (SLF) and the right anterior thalamic radiation (ATR).
      The reductions in FA values occurred in combination with elevated RD values in
      the bilateral SLF and decreased AD values in the bilateral ATR. FA values were
      negatively correlated with depression severity in the SLF and with illness
      duration in the right SLF and ATR. CONCLUSIONS: MDD patients had significant
      alterations in the WM micro-integrity of the left SLF and the right ATR.

PMID- 25065448
TI  - Partial nephrectomy for the treatment of renal cell carcinoma (RCC) and the risk
      of end-stage renal disease (ESRD).
AB  - OBJECTIVE: To assess whether radical nephrectomy (RN) compared with partial
      nephrectomy (PN) for the treatment of renal cell carcinoma (RCC) is associated
      with greater risk of end-stage renal disease (ESRD). PATIENTS AND METHODS: We
      performed a population-based, retrospective cohort study using linked
      administrative databases in the province of Ontario, Canada. We included
      individuals with pathologically confirmed RCC diagnosed between 1995 and 2010.
      Cox proportional hazards, propensity score, and competing risks models were used
      to assess the impact of treatment choice. The primary outcome was ESRD. Secondary
      outcomes included overall mortality, myocardial infarction, and new-onset chronic
      kidney disease (CKD). A modern cohort of patients (2003-2010) was analysed
      separately. RESULTS: We included 11,937 patients, of whom 2107 (18%) underwent
      PN. The median follow-up was 57 months. In the full cohort, type of surgery was
      not associated with the rate of ESRD, whereas PN was associated with a decreased
      likelihood of ESRD compared with RN in the modern cohort using a multivariable
      proportional hazards model [hazard ratio (HR) 0.44, 95% confidence interval (CI)
      0.25-0.75) or propensity score modelling (HR 0.48, 95% CI 0.27-0.82). PN was also
      associated with a lower risk of new-onset CKD (HR 0.48, 95% CI 0.41-0.57).
      CONCLUSIONS: Although it is well-known that RN is associated with more CKD than
      PN, we provide the first direct evidence that PN is associated with less ESRD
      requiring renal replacement therapy than RN in a modern cohort of patients with
      RCC.

PMID- 25065449
TI  - Landscape genomics of Populus trichocarpa: the role of hybridization, limited
      gene flow, and natural selection in shaping patterns of population structure.
AB  - Populus trichocarpa is an ecologically important tree across western North
      America. We used a large population sample of 498 accessions over a wide
      geographical area genotyped with a 34K Populus SNP array to quantify geographical
      patterns of genetic variation in this species (landscape genomics). We present
      evidence that three processes contribute to the observed patterns: (1)
      introgression from the sister species P. balsamifera, (2) isolation by distance
      (IBD), and (3) natural selection. Introgression was detected only at the margins
      of the species' distribution. IBD was significant across the sampled area as a
      whole, but no evidence of restricted gene flow was detected in a core of
      drainages from southern British Columbia (BC). We identified a large number of
      FST outliers. Gene Ontology analyses revealed that FST outliers are
      overrepresented in genes involved in circadian rhythm and response to red/far-red
      light when the entire dataset is considered, whereas in southern BC heat response
      genes are overrepresented. We also identified strong correlations between
      geoclimate variables and allele frequencies at FST outlier loci that provide
      clues regarding the selective pressures acting at these loci. 

PMID- 25065450
TI  - Post-traumatic growth among veterans in the USA: results from the National Health
      and Resilience in Veterans Study.
AB  - BACKGROUND: There is increasing recognition that, in addition to negative
      psychological consequences of trauma such as post-traumatic stress disorder
      (PTSD), some individuals may develop post-traumatic growth (PTG) following such
      experiences. To date, however, data regarding the prevalence, correlates and
      functional significance of PTG in population-based samples are lacking. METHOD:
      Data were analysed from the National Health and Resilience in Veterans Study, a
      contemporary, nationally representative survey of 3157 US veterans. Veterans
      completed a survey containing measures of sociodemographic, military, health and
      psychosocial characteristics, and the Posttraumatic Growth Inventory-Short Form.
      RESULTS: We found that 50.1% of all veterans and 72.0% of veterans who screened
      positive for PTSD reported at least 'moderate' PTG in relation to their worst
      traumatic event. An inverted U-shaped relationship was found to best explain the
      relationship between PTSD symptoms and PTG. Among veterans with PTSD, those with
      PTSD reported better mental functioning and general health than those without
      PTG. Experiencing a life-threatening illness or injury and re-experiencing
      symptoms were most strongly associated with PTG. In multivariable analysis,
      greater social connectedness, intrinsic religiosity and purpose in life were
      independently associated with greater PTG. CONCLUSIONS: PTG is prevalent among US
      veterans, particularly among those who screen positive for PTSD. These results
      suggest that there may be a 'positive legacy' of trauma that has functional
      significance for veterans. They further suggest that interventions geared toward
      helping trauma-exposed US veterans process their re-experiencing symptoms, and to
      develop greater social connections, sense of purpose and intrinsic religiosity
      may help promote PTG in this population.

PMID- 25065452
TI  - Effects of online cognitive treatment for problematic anger: a randomized
      controlled trial.
AB  - Problematic anger, which is common, has been associated with a wide range of
      negative interpersonal and intrapersonal consequences, including violent
      behaviour, relationship damage, health problems and low self-esteem. This article
      reports the results of the first randomized controlled trial of brief online
      cognitive treatment for anger. The sample included 75 adults who were randomly
      assigned to cognitive treatment or a waiting list control. The analyses with the
      59 participants who completed the post-intervention assessment at four weeks
      after the beginning of the intervention showed that individuals who received the
      intervention reported significantly lower anger levels than the control group at
      post-assessment. The treatment group showed a substantial decrease in anger from
      pre to post. The results suggest that brief online cognitive treatment can be
      effective for reducing problematic anger in adults. These findings provide an
      initial support for the development of internet-based cognitive treatment for
      problematic anger. 

PMID- 25065451
TI  - Overview of 71 European community-based initiatives against childhood obesity
      starting between 2005 and 2011: general characteristics and reported effects.
AB  - BACKGROUND: Community-based initiatives (CBIs) on childhood obesity are
      considered a good practice approach against childhood obesity. The European
      Commission called for an overview of CBIs implemented from 2005-2011. A survey
      was executed by the National Institute for Public Health and the Environment of
      the Netherlands, in collaboration with the World Health Organization Regional
      Office for Europe. The objective of this paper is to provide an overview of the
      European CBIs, as identified in the survey, presenting their general
      characteristics, applied strategies (separately for actions targeting the
      environment and/or directly the children's behaviour) and the reported effects on
      weight indicators. METHODS: Potentially eligible CBIs were identified by
      informants in 27 European Union countries, Iceland, Liechtenstein, Norway, and
      Switzerland, and through desk research. School based approaches could be included
      if they complied with criteria related to being 'community-based'. In total, 278
      potential eligible CBIs were identified and of these, 260 projects were
      approached. For 88 an electronic questionnaire was completed; of these 71 met all
      criteria. The included projects were reported by 15 countries. RESULTS: 66% of
      the 71 CBIs implemented actions in more than one setting or throughout the
      neighbourhood. Most frequently reported environmental actions were professional
      training (78%), actions for parents (70%), and changing the social (62%) and
      physical (52%) environment. Most frequently reported educational activities were
      group education (92%), general educational information (90%), and counselling
      sessions (58%). The vast majority (96%) implemented both environmental and
      individual strategies and about half of the CBIs reported a public-private
      partnership. Eight CBIs provided evidence supporting positive effects on weight
      indicators and/or overweight prevalence in a general population of children (aged
      6 to 12 yrs), and one CBI did not support this. Two of those CBIs were also
      conducted among adolescents (aged 12 to 16,5 yrs), but showed no effect in this
      age-group. CONCLUSIONS: Despite diversity of included CBIs, common
      characteristics were the application of integrated actions at a local level,
      aimed at changing the environment and the children's behaviour directly. Evidence
      supporting effectiveness on weight indicators is available, although the design
      and conduct of most of these studies were suboptimal (i.e. no control group, a
      small sample size, not random).

PMID- 25065453
TI  - Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in SLE
      patients: glycated-histones as likely trigger for SLE?
AB  - Histones are the most abundant proteins associated with genomic DNA. Recent
      observations show that histones are quite susceptible to non-enzymatic glycation
      which results in the generation of free radicals causing structural
      perturbations. In this study, our aim is to define the role of deoxyribose
      modified H2A histone in SLE initiation/progression. Glycation reaction was
      carried out by incubating H2A histone with 10 mM deoxyribose for 21 days at 37 
      degrees C. Structural changes in glycated-H2A were studied by various physico
      chemical techniques. The antigen-antibody interaction was studied by direct
      binding, inhibition ELISA and mobility shift assay. Deoxyribose-modified-H2A
      histone showed increased hyperchromicity and increased fluorescence intensity. CD
      results demonstrated almost 50% loss in alpha helix conformation as a consequence
      of glycation. This was supported by an increase in Tm value vis-a-vis thermal
      stability. Glycated-H2A showed cross linking in SDS-PAGE. SLE sera positive for
      anti-nDNA autoantibodies showed preference for deoxyribose-modified-H2A histone
      compared to native H2A histone or native DNA. Inhibition ELISA supported the
      above findings. Band shift assay further reiterated the preferential recognition
      of glycated-H2A over native H2A by SLE IgG autoantibodies. Deoxyribose-modified
      H2A histone exhibited damage as revealed by various physico-chemical studies.
      Glycation of H2A has resulted in the generation of neo-epitopes on H2A histone,
      which are preferably bound by SLE anti-nDNA autoantibodies. It implies that
      deoxyribose-modified-H2A may trigger immune response resulting in the generation
      of anti-glycated H2A antibodies with DNA cross reacting properties.

PMID- 25065454
TI  - Mechanisms underpinning inattention and hyperactivity: neurocognitive support for
      ADHD dimensionality.
AB  - BACKGROUND: Taxometric and behavioral genetic studies suggest that attention
      deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than
      a category. We extended these analyses by testing for the existence of putative
      ADHD-related deficits in basic information processing (BIP) and inhibitory-based
      executive function (IB-EF) in individuals in the subclinical and full clinical
      ranges. Consistent with the dimensional model, we predicted that ADHD-related
      deficits would be expressed across the full spectrum, with the degree of deficit
      linearly related to the severity of the clinical presentation. METHOD: A total of
      1547 children (aged 6-12 years) participated in the study. The Development and
      Well-Being Assessment (DAWBA) was used to classify children into groups according
      to levels of inattention and hyperactivity independently: (1) asymptomatic, (2)
      subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD.
      Neurocognitive performance was evaluated using a two-choice reaction time task
      (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived
      using a diffusion model (DM) for decomposition of reaction time (RT) and error
      data. RESULTS: Deficient BIP was found in subjects with minimal, moderate and
      full ADHD defined in terms of inattention (in both tasks) and
      hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit
      increased in a linear manner across increasingly severe presentations of ADHD. IB
      EF was unrelated to ADHD. CONCLUSIONS: Deficits in BIP operate at subclinical and
      clinical levels of ADHD. The linear nature of this relationship provides support
      for a dimensional model of ADHD in which diagnostic thresholds are defined in
      terms of clinical and societal burden rather than representing discrete
      pathophysiological states.

PMID- 25065455
TI  - Fractionation of visuo-spatial memory processes in bipolar depression: a
      cognitive scaffolding account.
AB  - BACKGROUND: Previous studies of neurocognitive performance in bipolar disorder
      (BD) have demonstrated impairments in visuo-spatial memory. The aim of the
      present study was to use an object-location memory (OLM) paradigm to assess
      specific, dissociable processes in visuo-spatial memory and examine their
      relationship with broader neurocognitive performance. METHOD: Fifty participants
      (25 patients with BD in a current depressive episode and 25 matched healthy
      controls) completed the OLM paradigm which assessed three different aspects of
      visuo-spatial memory: positional memory, object-location binding, and a combined
      process. Secondary neurocognitive measures of visuo-spatial memory, verbal
      memory, attention and executive function were also administered. RESULTS: BD
      patients were significantly impaired on all three OLM processes, with the largest
      effect in exact positional memory (d = 1.18, p < 0.0001). General deficits were
      also found across the secondary neurocognitive measures. Using hierarchical
      regression, verbal learning was found to explain significant variance on the OLM
      measures where object-identity was present (the object-location binding and
      combined processes) and accounted for the group difference. The group difference
      in precise positional memory remained intact. CONCLUSIONS: This study
      demonstrates that patients with bipolar depression manifest deficits in visuo
      spatial memory, with substantial impairment in fine-grain, positional memory. The
      differential profile of processes underpinning the visuo-spatial memory
      impairment suggests a form of 'cognitive scaffolding', whereby performance on
      some measures can be supported by verbal memory. These results have important
      implications for our understanding of the functional cognitive architecture of
      mood disorder.

PMID- 25065456
TI  - Evaluation of unintended effects in the composition of tomatoes expressing a
      human immunoglobulin A against rotavirus.
AB  - The production of neutralizing immunoglobulin A (IgA) in edible fruits as a means
      of oral passive immunization is a promising strategy for the inexpensive
      treatment of mucosal diseases. This approach is based on the assumption that the
      edible status remains unaltered in the immunoglobulin-expressing fruit, and
      therefore extensive purification is not required for mucosal delivery. However,
      unintended effects associated with IgA expression such as toxic secondary
      metabolites and protein allergens cannot be dismissed a priori and need to be
      investigated. This paper describes a collection of independent transgenic tomato
      lines expressing a neutralizing human IgA against rotavirus, a mucosal pathogen
      producing severe diarrhea episodes. This collection was used to evaluate possible
      unintended effects associated with recombinant IgA expression. A comparative
      analysis of protein and secondary metabolite profiles using wild type lines and
      other commercial varieties failed to find unsafe features significantly
      associated with IgA expression. Preliminary, the data indicate that formulations
      derived from IgA tomatoes are as safe for consumption as equivalent formulations
      derived from wild type tomatoes. 

PMID- 25065457
TI  - Preliminary survey of office-based opioid treatment practices and attitudes among
      psychiatrists never receiving buprenorphine training to those who received
      training during residency.
AB  - OBJECTIVE: To compare the characteristics, attitudes, and current prescribing
      practices of recently graduating psychiatrists who completed buprenorphine
      training during residency to those who never completed any training. METHODS: A
      total of 359 psychiatrists completing residency training between 2008 and 2011
      were recruited to complete an on-line survey. RESULTS: Responses from 93
      psychiatrists were included for a response rate of 25.9%. Psychiatrists
      completing any buprenorphine training during residency were more likely to be
      male and report more favorable views of OBOT with buprenorphine than compared to
      those who never completed any training. Twenty (38.5%) of those psychiatrists who
      completed training during residency reported the current prescribing of
      buprenorphine. CONCLUSIONS: Completion of buprenorphine training during residency
      may be a factor in shaping future attitudes towards OBOT and buprenorphine
      prescribing practices. Further research is needed to clarify the impact of
      buprenorphine training during residency. SCIENTIFIC SIGNIFICANCE: Buprenorphine
      training during residency training may be a contributing factor in shaping future
      physician attitudes towards office-based opioid treatment and buprenorphine
      prescribing practices.

PMID- 25065458
TI  - New treatment techniques for axillary hyperhidrosis.
AB  - Hyperhidrosis is a medical problem defined as perspiration in excess of what is
      normally needed to cool the body. The excessive production of sweat by the
      sudoriferous glands is independent of the process of thermoregulation. Techniques
      have recently appeared that make use of energy sources, in particular microwave
      devices and light (pulsed flashlamp or laser). The aim is to obtain very long
      lasting efficacy without notable side effects. Thermal Nd:YAG lasers used with an
      interstitial fiber, microwave devices, and photodynamic therapy appear to offer
      new treatment options for axillary hyperhidrosis. However, insertion of a laser
      fiber into tissue by means of a cannula may lead to complications if the
      procedure is not well mastered, as has been shown by numerous studies on laser
      lipolysis. The only microwave device available on the market is certainly
      interesting. Photodynamic therapy using eosin gel is an attractive technique. The
      energy source is a pulsed flashlamp, which many physicians have. Eosin gel is
      relatively easy to produce and these gels are already marketed in several
      countries. However, further clinical studies of larger series of patients and
      with longer follow-up are still needed to reach a definitive conclusion as to the
      value of this approach.

PMID- 25065459
TI  - Successful treatment of hypokalemic periodic paralysis with topiramate.

PMID- 25065461
TI  - Two-step thermal annealing improves the morphology of spin-coated films for
      highly efficient perovskite hybrid photovoltaics.
AB  - In this paper, we describe relationships between the morphologies and the power
      conversion efficiencies (PCE) of perovskite photovoltaics having a conventional p
      i-n heterojunction structure, indium tin oxide (ITO)/poly(3,4
      ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS)/CH(3)NH(3)PbI(3
      x)Cl(x)/PC(61)BM/Al. The PCE of such a device is highly dependent on the
      morphology of the perovskite film, which is governed by the concentrations of its
      precursors and the annealing conditions. A two-step annealing process allowed
      sufficient crystallization of the perovskite material, with a high coverage at a
      high precursor concentration. Relative to the device prepared using a one-step
      process (90  degrees C for 30 min), we observed a 60% increase in PCE for this
      optimized device. The corresponding devices exhibited extremely high stability
      after long-term storage (>1368 h) in the dark in a N2-filled glove box, with
      consistently high PCEs (AM 1.5 G, 100 mW cm(-2)) of up to 9.1%.

PMID- 25065462
TI  - Diabetes mellitus and atrial remodeling: mechanisms and potential upstream
      therapies.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical
      practice, and its prevalence has increasing substantially over the last decades.
      Recent data suggest that there is an increased risk of AF among the patients with
      diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM
      related AF and diabetic atrial remodeling are not fully understood. In this
      comprehensive review, we would like to summarize the potential relationship
      between diabetes and atrial remodeling, including structural, electrical, and
      autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones,
      probucol, ACEI/ARBs, may play an important role in the prevention and treatment
      of AF. Therefore, large prospective randomized, controlled trials and further
      experimental studies should be challengingly continued. 

PMID- 25065463
TI  - Bacteria under stress by complement and coagulation.
AB  - The complement and coagulation systems are two related protein cascades in plasma
      that serve important roles in host defense and hemostasis, respectively.
      Complement activation on bacteria supports cellular immune responses and leads to
      direct killing of bacteria via assembly of the Membrane Attack Complex (MAC).
      Recent studies have indicated that the coagulation system also contributes to
      mammalian innate defense since coagulation factors can entrap bacteria inside
      clots and generate small antibacterial peptides. In this review, we will provide
      detailed insights into the molecular interplay between these protein cascades and
      bacteria. We take a closer look at how these pathways are activated on bacterial
      surfaces and discuss the mechanisms by which they directly cause stress to
      bacterial cells. The poorly understood mechanism for bacterial killing by the MAC
      will be reevaluated in light of recent structural insights. Finally, we highlight
      the strategies used by pathogenic bacteria to modulate these protein networks.
      Overall, these insights will contribute to a better understanding of the host
      defense roles of complement and coagulation against bacteria. 

PMID- 25065464
TI  - Purpose, process, knowledge, and dignity in interdisciplinary projects.

PMID- 25065465
TI  - On collecting meta-analyses of schizophrenia and postage stamps.

PMID- 25065466
TI  - Graphene-based macroscopic assemblies and architectures: an emerging material
      system.
AB  - Due to the outstanding physicochemical properties arising from its truly two
      dimensional (2D) planar structure with a single-atom thickness, graphene exhibits
      great potential for use in sensors, catalysts, electrodes, and in biological
      applications, etc. With further developments in the theoretical understanding and
      assembly techniques, graphene should enable great changes both in scientific
      research and practical industrial applications. By the look of development, it is
      of fundamental and practical significance to translate the novel physical and
      chemical properties of individual graphene nanosheets into the macroscale by the
      assembly of graphene building blocks into macroscopic architectures with
      structural specialities and functional novelties. The combined features of a 2D
      planar structure and abundant functional groups of graphene oxide (GO) should
      provide great possibilities for the assembly of GO nanosheets into macroscopic
      architectures with different macroscaled shapes through various assembly
      techniques under different bonding interactions. Moreover, macroscopic graphene
      frameworks can be used as ideal scaffolds for the incorporation of functional
      materials to offset the shortage of pure graphene in the specific desired
      functionality. The advantages of light weight, supra-flexibility, large surface
      area, tough mechanical strength, and high electrical conductivity guarantee
      graphene-based architectures wide application fields. This critical review mainly
      addresses recent advances in the design and fabrication of graphene-based
      macroscopic assemblies and architectures and their potential applications.
      Herein, we first provide overviews of the functional macroscopic graphene
      materials from three aspects, i.e., 1D graphene fibers/ribbons, 2D graphene
      films/papers, 3D network-structured graphene monoliths, and their composite
      counterparts with either polymers or nano-objects. Then, we present the promising
      potential applications of graphene-based macroscopic assemblies in the fields of
      electronic and optoelectronic devices, sensors, electrochemical energy devices,
      and in water treatment. Last, the personal conclusions and perspectives for this
      intriguing field are given. 

PMID- 25065468
TI  - Iminosemiquinone radical ligands enable access to a well-defined redox-active
      Cu(II)-CF3 complex.
AB  - The reaction of a copper complex bearing iminosemiquinone ligands with a CF3(+)
      source provides an unprecedented Cu(II)-CF3 complex through ligand-based
      oxidation. Reactivity of this complex leads to nucleophilic trifluoromethylation
      of the ligand, suggesting an electronic interplay that results in a formal
      umpolung of the initial CF3(+). 

PMID- 25065467
TI  - The ubiquitin-associated domain of cellular inhibitor of apoptosis proteins
      facilitates ubiquitylation.
AB  - The cellular inhibitor of apoptosis (cIAP) proteins are essential RING E3
      ubiquitin ligases that regulate apoptosis and inflammatory responses. cIAPs
      contain a ubiquitin-associated (UBA) domain that binds ubiquitin and is
      implicated in the regulation of cell survival and proteasomal degradation. Here
      we show that mutation of the MGF and LL motifs in the UBA domain of cIAP1 caused
      unfolding and increased cIAP1 multimonoubiquitylation. By developing a UBA mutant
      that disrupted ubiquitin binding but not the structure of the UBA domain, we
      found that the UBA domain enhances cIAP1 and cIAP2 ubiquitylation. We demonstrate
      that the UBA domain binds to the UbcH5b~Ub conjugate, and this promotes RING
      domain-dependent monoubiquitylation. This study establishes ubiquitin-binding
      modules, such as the UBA domain, as important regulatory modules that can fine
      tune the activity of E3 ligases. 

PMID- 25065469
TI  - Adoption of cardiac resynchronization therapy in heart failure patients with
      postcardiac valve surgery or interventions?

PMID- 25065470
TI  - The development of a specialty: an interview with Dr. Mark C. Rogers, a
      pioneering pediatric intensivist.
AB  - Dr. Mark C. Rogers (1942-), Professor of Anesthesiology, Critical Care Medicine,
      and Pediatrics at the Johns Hopkins University, was recruited by the Department
      of Pediatrics at Johns Hopkins Hospital in 1977 to become the first director of
      its pediatric intensive care unit. After the dean of the medical school appointed
      him to chair the Department of Anesthesia in 1979, Rogers changed the course and
      culture of the department. He renamed it the Department of Anesthesiology and
      Critical Care Medicine, and developed a long-term strategy of excellence in
      clinical care, research, and education. However, throughout this period, he never
      lost his connection to pediatric intensive care. He has made numerous
      contributions to pediatric critical care medicine through research and his
      authoritative textbook, Rogers' Textbook of Pediatric Intensive Care. He
      established a training programme that has produced a plethora of leaders, helped
      develop the pediatric critical care board examination, and initiated the first
      World Congress of Pediatric Intensive Care. Based on a series of interviews with
      Dr. Rogers, this article reviews his influential career and the impact he made on
      developing pediatric critical care as a specialty. 

PMID- 25065471
TI  - In situ immunohistochemical detection of intracellular Mycoplasma salivarium in
      the epithelial cells of oral leukoplakia.
AB  - BACKGROUND: Mycoplasmas are the smallest free-living organisms; Mycoplasma
      salivarium and Mycoplasma orale are the most common species isolated from the
      oropharynx. Oral leukoplakia is the most prevalent potentially malignant disorder
      of the oral mucosa; its etiology has not been defined. Our previous study with
      DNA-binding fluorescent dye suggested the presence of mycoplasmas in the
      epithelial cells of leukoplakia tissue. OBJECTIVE: Our aim was to detect M.
      salivarium in the epithelial cells of leukoplakia by immunohistochemistry.
      DESIGN: We produced a polyclonal antibody (PAb) reactive to Mycoplasma by
      injecting a rabbit with M. salivarium cells (ATCC 23064) mixed with complete
      Freund's adjuvant and a monoclonal antibody specific to M. salivarium by
      injecting M. salivarium cells (ATCC 23557) mixed with complete Freund's adjuvant
      into the footpads of a rat. Then, we attempted to detect M. salivarium in the
      epithelium of leukoplakia tissues by immunohistochemistry. RESULTS: We obtained
      an antimycoplasma rabbit PAb reactive to all seven Mycoplasma species used in
      this study. Three hybridoma clones producing monoclonal antibodies specific to M.
      salivarium were obtained, and an M. salivarium-specific monoclonal antibody,
      designated 7-6H, was established. Immunohistochemistry with these antibodies
      revealed M. salivarium in the epithelial cells of leukoplakia with hyperplasia
      and hyperkeratosis on histology. PCR and sequencing verified the presence of M.
      salivarium DNA in the epithelial cells of leukoplakia. CONCLUSION: Intracellular
      M. salivarium was identified in the epithelial cells of leukoplakia.

PMID- 25065472
TI  - Is preference a predictor of enrichment efficacy in Galapagos tortoises
      (Chelonoidis nigra)?
AB  - It is widely acknowledged that environmental enrichment plays an important role
      in promoting the welfare of captive animals. However, a topic of debate is
      whether an animal's preference for an enrichment strategy is any indicator of its
      efficacy. In addition, relatively few studies have evaluated environmental
      enrichment strategies for non-mammalian species. In the present study, we
      compared the results of an observational evaluation of enrichment efficacy with
      the results of a paired-stimulus preference assessment for three Galapagos
      tortoises. In the observational study, object enrichment (boomer balls and a free
      flowing sprinkler) and keeper interactions (shell scrubbing and neck rubbing)
      were evaluated systematically for their effects on locomotion, species-typical
      behavior, aggressive and non-aggressive conspecific interactions, and enclosure.
      Preference assessments were subsequently conducted in which subjects could choose
      the enrichment strategy to be implemented. All subjects preferred keeper
      interactions consistently over object enrichment. Our results suggest that
      enrichment preference was a variable predictor of efficacy across enrichment
      species-typical behavior, activity levels, enclosure use, and aggressive and non
      aggressive conspecific interactions strategies. Preference predicted efficacy for
      promoting species-typical behavior (1/3 subjects), activity levels (2/3
      subjects), and enclosure use (2/3 subjects), but not conspecific interactions
      (0/3 subjects). The results suggest that preference may be an efficient predictor
      of enrichment efficacy when daily observational evaluations are not practical;
      however, the predictive utility of preference assessments may depend on the
      behavioral goal of the enrichment strategy. We discuss the need for future
      research examining the relationship between preference and enrichment efficacy-as
      well as other potential indicators of enrichment effectiveness-in captive
      animals.

PMID- 25065473
TI  - The investigation of the oxidative stress-related parameters in type 2 diabetes
      mellitus.
AB  - OBJECTIVE: Oxidative stress, defined as an imbalance between reactive oxygen
      species production and breakdown by endogenous antioxidants, is closely
      associated with diabetes mellitus. The diabetes is characterized by hyperglycemia
      together with biochemical alterations of glucose and lipid peroxidation.
      Oxidative stress has been implicated in the pathogenesis of type 2 diabetes and
      its complications. METHODS: This study was conducted to investigate the variation
      in oxidative stress-related parameters in type 2 diabetes. Blood serum samples
      were collected from diabetes patients and nondiabetes healthy controls. Glucose
      concentrations, levels of glycated hemoglobin (A1C) and serum oxidative stress
      markers (glucose-6-phosphate dehydrogenase [G6PDH], malondialdehyde [MDA],
      glutathione [GSH], glutathione reductase [GR], glutathione peroxidase [GPx] and
      superoxide dismutase [SOD]) were estimated. RESULTS: Fasting serum glucose
      concentration in type 2 diabetes patients of both sexes was increased
      significantly as compared with the healthy controls. Level of A1C was greater
      than standards. Significant elevation in MDA level and depletion in GSH content
      were observed in diabetes patients in comparison with controls. The diminution in
      G6PDH activity was accompanied in part by a decrease in the antioxidative enzymes
      activities (GPx and GR), and in part by an increase in SOD activity in all
      diabetes patients as compared with the control group. The regression analysis
      showed no correlation between diabetes duration and severity of oxidative stress;
      however, there was a significant association between A1C and severity of
      oxidative stress. CONCLUSIONS: The present study shows that there is an oxidative
      stress state in type 2 diabetes patients compared with healthy subjects. Our data
      suggest that chronic hyperglycemia causes a significant change in oxidative
      stress markers.

PMID- 25065474
TI  - Implementation of resources to support patient physical activity through diabetes
      centres in Atlantic Canada: the effectiveness of toolkit-based physical activity
      counselling.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of
      toolkit-based physical activity counselling on physical activity and exercise
      participation of type 2 diabetes patients attending diabetes centres in Atlantic
      Canada. METHODS: Patients with type 2 diabetes (n=198) were recruited to a
      quasiexperimental study comparing the effectiveness of counselling by persons
      trained to use a physical activity and exercise resource manual (i.e. toolkit)
      vs. a standard of care counselling situation. Effectiveness was assessed through
      questionnaires completed by patients, and clinical data were extracted from
      patient charts before and 6 months after a single appointment with a diabetes
      educator. Primary outcome measures were patient self-reported physical activity
      and exercise levels, efficacy perceptions and mean glycated hemoglobin. RESULTS:
      There were no significant differences in primary outcomes over time. Subanalyses
      of the toolkit-counselled patients revealed a significant interaction for
      moderate-to-vigorous physical activity (MVPA [p<0.0001]), whereby patients who
      were not meeting Canadian Diabetes Association guidelines for physical activity
      at baseline (i.e. <150 MVPA a week; n=44) increased physical activity (from 20+/
      23 to 120+/-30 minutes) and patients who were active at baseline (i.e. >150 MVPA
      a week; n=22) decreased physical activity (from 444+/-32 to 161+/-41 minutes) at
      6 months. CONCLUSIONS: A single counselling appointment using the toolkit did not
      elicit significant changes in physical activity or clinical outcomes measured 6
      months later when compared with standard care condition; however, increased
      physical activity was observed for patients who were inactive at baseline.
      Repeated counselling or more intensive strategies may be required to increase
      patient physical activity levels and produce clinical outcomes.

PMID- 25065475
TI  - Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2
      diabetes mellitus.
AB  - Here, we discuss certain practical issues related to use of insulin degludec, a
      new long-acting basal insulin analogue. Degludec provides uniform ("peakless")
      action that extends over more than 24 hours and is highly consistent from dose to
      dose. Like the 2 previously available basal analogues (detemir and glargine),
      degludec is expected to simplify dose adjustment and enable patients to reach
      their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials
      involving type 1 and type 2 diabetes have demonstrated that degludec was
      noninferior to glargine in allowing patients to reach a target glycated
      hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less
      frequently with degludec. In addition, when dosing intervals vary substantially
      from day to day, degludec continues to be effective and to maintain a low rate of
      nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of
      nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to
      improve patient and caregiver confidence in the stability of glycemic control. A
      dedicated injector, the FlexTouch prefilled pen, containing degludec 200
      units/mL, will be recommended for most patients with type 2 diabetes. Degludec
      will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by
      patients requiring smaller basal insulin doses, including most patients with type
      1 diabetes. 

PMID- 25065476
TI  - Implementation of resources to support patient physical activity through diabetes
      centres in Nova Scotia: the effectiveness of enhanced support for exercise
      participation.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of
      enhancing support for physical activity counselling and exercise participation at
      diabetes centres in Nova Scotia on physical activity and exercise behaviours and
      clinical outcomes in patients with type 2 diabetes mellitus. METHODS: In all, 180
      patients at 8 diabetes centres participated in this observational study. A range
      of enhanced supports for exercise were offered at these centres. A kinesiologist
      was added to the diabetes care team to primarily provide extra physical activity
      counselling and exercise classes. Patient physical activity and exercise levels,
      efficacy perceptions and mean glycated hemoglobin (A1C) were evaluated at
      baseline and 6 months. We compared changes in these variables for patients who
      participated in the enhanced supports versus patients who did not. RESULTS:
      Participants who attended exercise classes (n=46), increased moderate physical
      activity by 27% and doubled resistance exercise participation (1.0+/-1.8 to 2.0+/
      2.1 days per week) whereas those who did not attend exercise classes (n=49)
      reduced moderate physical activity by 26% and did not change resistance exercise
      participation (interactions, p=0.04 and p=0.07, respectively). Patients who
      received resistance band instruction (n=15) from a kinesiologist had reductions
      in A1C (from 7.5+/-1.4 to 7.1+/-1.2; p=0.04), whereas other subgroups did not
      have significant changes in A1C. CONCLUSIONS: Offering enhanced support for
      exercise at diabetes centres produced improvements in physical activity and
      exercise in type 2 diabetes patients. Resistance band instruction from a
      kinesiologist combined with participating in a walking and resistance training
      program improved glycemic control, which underscores the importance of including
      exercise professionals in diabetes management.

PMID- 25065477
TI  - Identifying persons with diabetes who could benefit from a palliative approach to
      care.
AB  - OBJECTIVE: To determine the need for diabetes mellitus palliative care, we
      identified persons with a diagnosis of diabetes who accessed palliative care
      programs and those who may have benefited from a palliative approach to care.
      METHODS: This retrospective, descriptive research used 6 linked databases
      comprising 66 634 Nova Scotians from 3 health districts who died between 1995 and
      2009, each with access to a palliative care program and diabetes centres.
      RESULTS: The percentage of persons with diabetes enrolled in palliative care
      increased from 3.2% in 1995 to 34.3% in 2009; 31.5% were enrolled within their
      last 2 weeks of life. Most did not have their diabetes recorded in palliative
      data. Among the 5353 persons with a diagnosis of diabetes who died between 2005
      and 2009, 61.0% were in the Diabetes Care Program of Nova Scotia registry. An
      additional 19.6% were identified in the Cardiovascular Health Nova Scotia
      registry, and a further 3.7% in palliative data. Applying the criteria of
      Rosenwax et al to the 5353, 65.8% to 97.9% may have benefitted from a palliative
      approach. CONCLUSIONS: Rates of palliative enrollment for persons with diabetes
      are increasing. Diabetes care providers need to prepare patients and their
      families for changes in diabetes management that will be beneficial as end of
      life approaches. Collaboration among chronic disease programs, palliative care
      and primary care is advised to identify persons at end of life who have diabetes
      and to develop and implement care guidelines for this population.

PMID- 25065478
TI  - Feasibility of treating aged polycyclic aromatic hydrocarbons (PAHs)-contaminated
      soils using ethyl lactate-based Fenton treatment via parametric and kinetic
      studies.
AB  - This study focuses on the feasibility of treating aged polycyclic aromatic
      hydrocarbons (PAHs)-contaminated soils using ethyl lactate (EL)-based Fenton
      treatment via a combination of parametric and kinetic studies. An optimised
      operating condition was observed at 66.7 M H2O2 with H2O2/Fe(2+) of 40:1 for low
      soil organic carbon (SOC) content and mildly acidic soil (pH 6.2), and 10:1 for
      high SOC and very acidic soil (pH 4.4) with no soil pH adjustment. The desorption
      kinetic was only mildly shifted from single equilibrium to dual equilibrium of
      the first-order kinetic model upon ageing. Pretreatment with EL fc = 0.60 greatly
      reduced the mass transfer coefficient especially for the slow desorbed fraction
      (kslow) of high molecular weight (HMW) PAHs, largely contributed by the
      concentration gradient created by EL-enhanced solubility. As the major desorption
      obstacle was almost fully overcome by the pretreatment, the pseudo-first-order
      kinetic reaction rate constant of PAHs degradation of aged soils was
      statistically discernible from that of freshly contaminated soils but slightly
      reduced in high SOC and high acidity soil. Stabilisation of H2O2 by EL addition
      in combination with reduced Fe(2+) catalyst were able to slow the decomposition
      rate of H2O2 even at higher soil pH.

PMID- 25065479
TI  - Phenol degradation using the mixed material clay/Fe immobilized on glass slides.
AB  - The mixed material clay/Fe was prepared and immobilized on glass slides and
      calcined at 550 and 750  degrees C. The calcined material X-ray powder pattern
      (XRD) diffractograms indicate that there is no intercalation of iron compounds
      inside the lamella clay. The experimental design revealed that the most suitable
      phenol degradation conditions were obtained using the material calcined at 750 
      degrees C in a pH 7 and 140 mg/L of hydrogen peroxide solution. The material
      MMAFe750 showed excellent performance as a catalyst for Fenton-like reaction; in
      125 min, 50 % of phenol was removed in the absence of leaching-supported iron.
      These results indicate that the reaction occurs by a heterogeneous process.
      Furthermore, the material showed no loss of catalytic activity after five
      degradation studies. It was noted that the adsorption of phenol in the
      synthesized materials does not occur and the mixed material is strongly adsorbed
      onto glass slides.

PMID- 25065480
TI  - Assessment of hematological profiles of adult male athletes from two different
      air pollutant zones of West Bengal, India.
AB  - Health effects from air pollution are severe concern of today's world. The study
      was undertaken to assess the effects of air pollution on hematological profiles
      of trained and untrained males of West Bengal. The sample consisted of 60
      sprinters, 60 footballers, and 120 untrained males, subdivided into two groups
      from two zones, namely, Tollygunge and Sonarpur. Suspended particulate matter
      (SPM), respirable particulate matter (RPM), oxides of sulfur (SOx), and oxides of
      nitrogen (NOx) of ambient air were monitored for both zones. Height and weight of
      all the subjects were measured. Venous blood sample was drawn from the cubital
      vein, and the red blood cell count (TC), packed cell volume (PCV), hemoglobin
      (Hb) concentration, mean corpuscular volume (MCV), and mean corpuscular
      hemoglobin concentration (MCHC) were determined by standard methods. Results
      revealed that SPM, RPM, SOx, and NOx concentrations were significantly higher in
      the Tollygunge area than Sonarpur. TC, PCV, and Hb concentration of untrained
      males were significantly higher than footballers in both regions but no
      significant difference were observed when compared with sprinters, except the Hb
      concentration in the Tollygunge zone. On the other hand, all hematological
      parameters of both trained and untrained males were significantly higher in the
      Sonarpur area than Tollygunge. It was concluded that environmental air pollutants
      might influence hematological profile adversely both in trained and sedentary
      males. However, further investigation in this area is needed. 

PMID- 25065481
TI  - Profenofos insecticide degradation by novel microbial consortium and isolates
      enriched from contaminated chili farm soil.
AB  - Profenofos (PF) is one of the heavily used organophosphorus pesticides (OPPs) of
      which its contamination is ubiquitous in an agricultural area. This study aims to
      acquire and characterize PF-degrading bacterial cultures from contaminated soil.
      OPP degradation by the novel isolates was then investigated. The experiment was
      performed at the initial PF concentration of 20 mg/L. The result showed that the
      enriched consortium comprised three predominant PF-degrading strains designated
      as PF1, PF2, and PF3. The isolates (PF1, PF2, and PF3) were characterized as
      Pseudomonas plecoglossicida, Pseudomonas aeruginosa, and P. aeruginosa,
      respectively. A consortium and all isolates could utilize PF as a sole carbon
      source with PF removal of more than 90% via a hydrolysis process. The bacterial
      growth and PF degradation rates followed the first-order kinetic reaction with
      the rates of 0.4 to 2.7/h and 0.15 to 1.96/h, respectively. Additional carbon
      supplement deteriorated PF biodegradation. The enriched cultures were also
      capable for degrading chlorpyrifos and dicrotophos pesticides (33-73% removal).
      The results indicated that the consortium and isolates are efficient for PF and
      other OPP degradation and have potential for PF remediation.

PMID- 25065483
TI  - Pigmentary demarcation lines of pregnancy in two Caucasian women.

PMID- 25065482
TI  - Mining in New Caledonia: environmental stakes and restoration opportunities.
AB  - New Caledonia is a widely recognised marine and terrestrial biodiversity hot
      spot. However, this unique environment is under increasing anthropogenic
      pressure. Major threats are related to land cover change and include fire, urban
      sprawling and mining. Resulting habitat loss and fragmentation end up in serious
      erosion of the local biodiversity. Mining is of particular concern due to its
      economic significance for the island. Open cast mines were exploited there since
      1873, and scraping out soil to access ores wipes out flora. Resulting
      perturbations on water flows and dramatic soil erosion lead to metal-rich
      sediment transport downstream into rivers and the lagoon. Conflicting
      environmental and economic aspects of mining are discussed in this paper.
      However, mining practices are also improving, and where impacts are inescapable
      ecological restoration is now considered. Past and ongoing experiences in the
      restoration of New Caledonian terrestrial ecosystems are presented and discussed
      here. Economic use of the local floristic diversity could also promote
      conservation and restoration, while providing alternative incomes. In this
      regard, Ecocatalysis, an innovative approach to make use of metal
      hyperaccumulating plants, is of particular interest. 

PMID- 25065484
TI  - Circulating factors are involved in hypoxia-induced hepcidin suppression.
AB  - Hepcidin transcription is strongly down-regulated under hypoxic conditions,
      however whether hypoxia inhibits hepcidin directly or indirectly is still
      unknown. We investigated the time course of hypoxia-mediated hepcidin down
      regulation in vivo in healthy volunteers exposed to hypobaric hypoxia at high
      altitude and, based on the hypothesis that circulating factors are implicated in
      hepcidin inhibition, we analyzed the effect of sera of these volunteers exposed
      to normoxia and hypoxia on hepcidin expression in Huh-7 cell lines. Hypoxia led
      to a significant hepcidin down-regulation in vivo that was almost complete within
      72h of exposure and followed erythropoietin induction. This delay in hepcidin
      down-regulation suggests the existence of soluble factor/s regulating hepcidin
      production. We then stimulated HuH-7 cells with normoxic and hypoxic sera to
      analyze the effects of sera on hepcidin regulation. Hypoxic sera had a
      significant inhibitory effect on hepcidin promoter activity assessed by a
      luciferase assay, although the amount of such decrease was not as relevant as
      that observed in vivo. Cellular mRNA analysis showed that a number of volunteers'
      sera inhibited hepcidin expression, concurrently with ID1 inhibition, suggesting
      that inhibitory factor(s) may act through the SMAD-pathway. 

PMID- 25065486
TI  - A novel UPLC-MS/MS method for sensitive quantitation of boldine in plasma, a
      potential anti-inflammatory agent: application to a pharmacokinetic study in
      rats.
AB  - Boldine is a potential anti-inflammatory agent found in several different plants.
      Published bioanalytical methods using HPLC with ultraviolet and fluorescent
      detection lacked enough sensitivity and required tedious sample preparation
      procedures. Herein, we describe the development of a novel ultra-high performance
      LC with MS/MS for determination of boldine in plasma. Boldine in plasma was
      recovered by liquid-liquid extraction using 1 mL of methyl tert-butyl ether.
      Chromatographic separation was performed on a C18 column at 45 degrees C, with a
      gradient elution consisting of acetonitrile and water containing 0.1% (v/v)
      formic acid at a flow rate of 0.3 mL/min. The detection was performed on an
      electrospray triple-quadrupole MS/MS by positive ion multiple reaction monitoring
      mode. Good linearity (r(2) > 0.9926) was achieved in a concentration range of
      2.555-2555 ng/mL with a lower limit of quantification of 2.555 ng/mL for boldine.
      The intra- and inter-day precisions of the assay were 1.2-6.0 and 1.8-7.4%
      relative standard deviation with an accuracy of -6.0-8.0% relative error. This
      newly developed method was successfully applied to a single low-dose
      pharmacokinetic study in rats and was demonstrated to be simpler and more
      sensitive than the published methods, allowing boldine quantification in reduced
      plasma volume.

PMID- 25065485
TI  - Prenatal maternal immune disruption and sex-dependent risk for psychoses.
AB  - BACKGROUND: Previous studies suggest that abnormalities in maternal immune
      activity during pregnancy alter the offspring's brain development and are
      associated with increased risk for schizophrenia (SCZ) dependent on sex. METHOD:
      Using a nested case-control design and prospectively collected prenatal maternal
      sera from which interleukin (IL)-1beta, IL-8, IL-6, tumor necrosis factor (TNF)
      alpha and IL-10 were assayed, we investigated sex-dependent associations between
      these cytokines and 88 psychotic cases [SCZ = 44; affective psychoses (AP) = 44]
      and 100 healthy controls from a pregnancy cohort followed for > 40 years.
      Analyses included sex-stratified non-parametric tests adjusted for multiple
      comparisons to screen cytokines associated with SCZ risk, followed by deviant
      subgroup analyses using generalized estimating equation (GEE) models. RESULTS:
      There were higher prenatal IL-6 levels among male SCZ than male controls, and
      lower TNF-alpha levels among female SCZ than female controls. The results were
      supported by deviant subgroup analyses with significantly more SCZ males with
      high IL-6 levels (>highest quartile) compared with controls [odd ratio (OR)75 =
      3.33, 95% confidence interval (CI) 1.13-9.82], and greater prevalence of low TNF
      alpha levels (<lowest quartile) among SCZ females compared with their controls
      (OR25 = 6.30, 95% CI 1.20-33.04) and SCZ males. Higher levels of IL-6 were only
      found among SCZ compared with AP cases. Lower TNF-alpha levels (non-significant)
      also characterized female AP cases versus controls, although the prevalence of
      the lowest levels was higher in SCZ than AP females (70% v. 40%), with no effect
      in SCZ or AP males. CONCLUSIONS: The results underscore the importance of
      immunologic processes affecting fetal brain development and differential risk for
      psychoses depending on psychosis subtype and offspring sex.

PMID- 25065487
TI  - Some evidence for health-related marriage selection.
AB  - OBJECTIVES: Married people live longer and are healthier than unmarried people.
      This can be explained in terms of marriage protection and marriage selection. The
      aim of the present study was to examine the direct effect of marriage selection
      on health status. METHODS: Data were collected from the archives of the Lower
      Silesian Medical Center (DOLMED) in Wroclaw, Poland. The sample consisted of
      2,265 adult (never married or currently married) men. Subjects were assigned to
      categories for selected variables, including age, level of education, military
      category upon conscription, height, hearing acuity, and visual acuity. Military
      category, objective data gathered upon military conscription at age 18, was used
      to assess initial health status. To identify any relationships between marital
      status and health status, generalized linear models with binomially distributed
      dependent variable were used. RESULTS: The never-married subjects were more
      likely to have been assigned to lower military categories, which indicates that
      their health status at age 18 was inferior to those conscripts who would later
      marry. Hearing acuity and visual acuity were generally worse in never-married
      subjects than in married subjects. Never-married subjects were also more likely
      to be short and less likely to be tall. CONCLUSIONS: The results provide evidence
      for direct health-related marriage selection in men between 25 and 60 years of
      age. Poor health status reduces the likelihood of marriage.

PMID- 25065488
TI  - Liver regeneration after living donor transplantation: adult-to-adult living
      donor liver transplantation cohort study.
AB  - Adult-to-adult living donors and recipients were studied to characterize patterns
      of liver growth and identify associated factors in a multicenter study. Three
      hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor
      Liver Transplantation Cohort Study (A2ALL) receiving transplants between March
      2003 and February 2010 were included. Potential predictors of 3-month liver
      volume included total and standard liver volumes (TLV and SLV), Model for End
      Stage Liver Disease (MELD) score (in recipients), the remnant and graft size,
      remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR),
      remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676 +/- 251
      g (mean +/- SD), and percentage reconstitution was 80% +/- 13%. Among recipients,
      GRWR was 1.3% +/- 0.4% (8 < 0.8%). Graft weight was 60% +/- 13% of SLV. Three
      month absolute growth was 549 +/- 267 g, and percentage reconstitution was 93% +/
      18%. Predictors of greater 3-month liver volume included larger patient size
      (donors and recipients), larger graft volume (recipients), and larger TLV
      (donors). Donors with the smallest remnant/TLV ratios had larger than expected
      growth but also had higher postoperative bilirubin and international normalized
      ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had
      smaller 3-month liver volumes than recipients adjusted for patient size, remnant
      or graft volume, and TLV or SLV (P = 0.004). Recipient graft failure in the first
      90 days was predicted by poor graft function at day 7 (HR = 4.50, P = 0.001) but
      not by GRWR or graft fraction (P > 0.90 for each). Both donors and recipients had
      rapid yet incomplete restoration of tissue mass in the first 3 months, and this
      confirmed previous reports. Recipients achieved a greater percentage of expected
      total volume. Patient size and recipient graft volume significantly influenced 3
      month volumes. Importantly, donor liver volume is a critical predictor of the
      rate of regeneration, and donor remnant fraction affects postresection function.
      Liver Transpl 21:79-88, 2015. (c) 2014 AASLD. 

PMID- 25065489
TI  - Buprenorphine pharmacotherapy and behavioral treatment: comparison of outcomes
      among prescription opioid users, heroin users and combination users.
AB  - Most research examining buprenorphine has been conducted with heroin users. Few
      studies have examined buprenorphine pharmacotherapy for prescription opioid
      users. Data were from a randomized controlled trial of behavioral treatment
      provided for 16weeks on a platform of buprenorphine pharmacotherapy and
      medication management. We compared heroin (H, n=54), prescription opioid (PO,
      n=54) and combination heroin+prescription opioid (POH, n=71) users to test the
      hypothesis that PO users will have better treatment outcomes compared with heroin
      users. The PO group provided more opioid-negative urine drug screens over the
      combined treatment period (PO:70%, POH:40%, H:38%, p<0.001) and at the end of the
      combined treatment period (PO:65%, POH:31%, H:33%, p<0.001). Retention was lowest
      in the H group (PO:80%, POH:65%, H:57%, p=0.039). There was no significant
      difference in buprenorphine dose between the groups. PO users appear to have
      better outcomes in buprenorphine pharmacotherapy compared to those reporting any
      heroin use, confirming that buprenorphine pharmacotherapy is effective in PO
      users. 

PMID- 25065490
TI  - Catalytic functionalization of methane and light alkanes in supercritical carbon
      dioxide.
AB  - The development of catalytic methods for the effective functionalization of
      methane yet remains a challenge. The best system known to date is the so-called
      Catalytica Process based on the use of platinum catalysts to convert methane into
      methyl bisulfate with a TOF rate of 10(-3) s. In this contribution, we report a
      series of silver complexes containing perfluorinated tris(indazolyl)borate
      ligands that catalyze the functionalization of methane into ethyl propionate upon
      reaction with ethyl diazoacetate (EDA) by using supercritical carbon dioxide
      (scCO2) as the reaction medium. The employment of this reaction medium has also
      allowed the functionalization of ethane, propane, butane, and isobutane.

PMID- 25065491
TI  - Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine
      derivatives as new potential PET tracers for imaging of p38alpha mitogen
      activated protein kinase.
AB  - The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5
      methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5
      (ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate
      (10b) and corresponding precursors 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5
      methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11a), methyl 4-(2-methyl-5
      (ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic
      acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic
      acid in multiple steps with moderate to excellent yields. The target tracer
      [(11)C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1
      f][1,2,4]triazine-6-carboxylate ([(11)C]10a) and [(11)C]methyl 4-(2-methyl-5
      (ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate
      ([(11)C]10b) were prepared from their corresponding precursors with [(11)C]CH3OTf
      under basic condition through O-[(11)C]methylation and isolated by a simplified
      solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of
      bombardment (EOB) with 185-555 GBq/MUmol specific activity at end of synthesis
      (EOS).

PMID- 25065492
TI  - 2-Alkyloxazoles as potent and selective PI4KIIIbeta inhibitors demonstrating
      inhibition of HCV replication.
AB  - Synthesis and SAR of 2-alkyloxazoles as class III phosphatidylinositol-4-kinase
      beta (PI4KIIIbeta) inhibitors is described. These compounds demonstrate that
      inhibition of PI4KIIIbeta leads to potent inhibition of HCV replication as
      observed in genotype (GT) 1a and 1b replicon and GT2a JFH1 virus assays in vitro.

PMID- 25065493
TI  - The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1
      hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting beta2
      adrenoceptor agonist.
AB  - The optimisation of two series of 4-hydroxybenzothiazolone derived beta2
      adrenoceptor agonists, bearing alpha-substituted cyclopentyl and beta-phenethyl
      amino-substituents, as inhaled long-acting bronchodilators is described.
      Analogues were selected for synthesis using a lipophilicity based hypothesis to
      achieve the targeted rapid onset of action in combination with a long duration of
      action. The profiling of the two series led to identification of the alpha
      substituted cyclopentyl analogue 2 as the optimal compound with a comparable
      profile to the inhaled once-daily long-acting beta2-adrenoceptor agonist
      indacaterol. On the basis of these data 2 was promoted as the backup development
      candidate to indacaterol from the Novartis LABA project. 

PMID- 25065494
TI  - The architecture of the chess player's brain.
AB  - The game of chess can be seen as a typical example for an expertise task
      requiring domain-specific training and experience. Despite intensive behavioural
      studies the neural underpinnings of chess performance and expertise are not
      entirely understood. A few functional neuroimaging studies have shown that expert
      chess players recruit different psychological functions and activate different
      brain areas while they are engaged in chess-related activities. Based on this
      functional literature, we predicted to find morphological differences in a
      network comprised by parietal and frontal areas and especially the occipito
      temporal junction (OTJ), fusiform gyrus, and caudate nucleus. Twenty expert chess
      players and 20 control subjects were investigated using voxel-based and surface
      based morphometry as well as diffusion tensor imaging. Grey matter volume and
      cortical thickness were reduced in chess players compared with those of control
      men in the OTJ and precunei. The volumes of both caudate nuclei were not
      different between groups, but correlated inversely with the years of chess
      playing experience. Mean diffusivity was increased in chess players compared with
      that of controls in the left superior longitudinal fasciculus and the Elo score
      (a chess tournament ranking) was inversely related to mean diffusivity within the
      right superior longitudinal fasciculus. To the best of our knowledge we showed
      for the first time that there are specific differences in grey and white matter
      morphology between chess players and control subjects in brain regions associated
      with cognitive functions important for playing chess. Whether these anatomical
      alterations are the cause or consequence of the intensive and long-term chess
      training and practice remains to be shown in future studies. 

PMID- 25065495
TI  - Novelty processing and memory formation in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is characterized by a degeneration of
      nigrostriatal dopaminergic cells, resulting in dopamine depletion. This depletion
      is counteracted through dopamine replacement therapy (DRT). Dopamine has been
      suggested to affect novelty processing and memory, which suggests that these
      processes are also implicated in PD and that DRT could affect them. OBJECTIVE: To
      investigate word learning and novelty processing in patients with PD as indexed
      by the P2 and P3 event-related potential components, and the role of DRT in these
      processes. METHODS: 21 patients with PD and 21 matched healthy controls were
      included. Patients with PD were tested on and off DRT in two sessions in a
      counterbalanced design, and healthy controls were tested twice without
      intervention. Electroencephalogram (EEG) was measured while participants
      performed a word learning Von Restorff task. RESULTS: Healthy controls showed the
      typical Von Restorff effect, with better memory for words that were presented in
      novel fonts, than for words presented in standard font. Surprisingly, this effect
      was reversed in the patients with PD. In line with the behavioral findings, the
      P3 was larger for novel than for standard font words in healthy controls, but not
      in patients with PD. For both groups the P2 and P3 event-related components were
      larger for recalled versus forgotten words. DRT did not affect these processes.
      CONCLUSIONS: Learning of novel information is compromised in patients with PD.
      Likewise, the P2 and P3 components that predict successful memory encoding are
      reduced in PD patients. This was true both on and off DRT, suggesting that these
      findings reflect abnormalities in learning and memory in PD that are not resolved
      by dopaminergic medication.

PMID- 25065497
TI  - Ion channel TRPM8 promotes hypoxic growth of prostate cancer cells via an O2 
      independent and RACK1-mediated mechanism of HIF-1alpha stabilization.
AB  - The growth adaptation of cancer cells to a hypoxic tumour microenvironment is
      mostly regulated by hypoxia-induced transcription factor HIF-1. HIF-1
      transcriptional activity is strictly controlled by protein levels of the HIF
      1alpha subunit, which is tightly regulated by a well-characterized O2 -dependent
      ubiquitin ligase-proteasomal degradation pathway. The cold-sensitive Ca(2+)
      channel protein TRPM8 exhibits increased expression in advanced prostate cancer.
      However, its exact functional roles in prostate cancer growth regulation are
      unclear and controversial. In this work, we show that TRPM8 promotes in vitro
      hypoxic growth capacities, drug resistance, and in vivo tumourigenicity,
      accompanied with enhanced HIF-1alpha protein levels. These effects are further
      potentiated by TRPM8 agonists but suppressed by TRPM8 gene knockdown and blocking
      with antagonists or TRPM8 antibody. TRPM8-induced suppression of HIF-1alpha
      ubiquitination and enhanced HIF-1 transactivation were attenuated by forced RACK1
      expression and TRPM8 overexpression reduced phospho-RACK1 levels, thus affecting
      its dimerization status, and promoted RACK1 binding to HIF-1alpha and
      calcineurin. These data indicate that TRPM8-induced increase of HIF-1alpha
      protein in hypoxia- or normoxia-exposed prostate cancer cells was mediated
      through a newly characterized Ca(2+) -dependent but O2 -independent mechanism
      involving binding of RACK1 to HIF-1alpha and RACK1-mediated ubiquitination of HIF
      1alpha. Collectively, our study not only provides a mechanistic insight into how
      TRPM8 promotes the hypoxic growth adaptation of cancer cells via its promotion of
      RACK1-mediated stabilization of HIF-1alpha but also suggests a potential
      therapeutic strategy for prostate cancer by targeting TRPM8.

PMID- 25065498
TI  - The global relevance of disease management programmes for heart failure.

PMID- 25065496
TI  - Retinoblastoma. Fifty years of progress. The LXXI Edward Jackson Memorial
      Lecture.
AB  - PURPOSE: To review the progress made in understanding the genetic basis,
      molecular pathology, and treatment of retinoblastoma since the previous Jackson
      lecture on the topic was published 50 years ago. DESIGN: Perspective based on
      personal experience and the literature. METHODS: The literature regarding
      retinoblastoma was reviewed since 1963. Advances in understanding the biology and
      treatment of retinoblastoma provided context through the author's clinical,
      pathologic, and research experiences. RESULTS: Retinoblastoma was first
      identified in the 1500s and defined as a unique clinicopathologic entity in 1809.
      Until the mid-1900s, knowledge advanced sporadically, with technological
      developments of ophthalmoscopy and light microscopy, and with the introduction of
      surgical enucleation, chemotherapy, and radiation therapy. During the last 50
      years, research and treatment have progressed at an unprecedented rate owing to
      innovations in molecular biology and the development of targeted therapies.
      During this time period, the retinoblastoma gene was discovered; techniques for
      genetic testing for retinoblastoma were developed; and plaque brachytherapy,
      chemoreduction, intra-arterial chemotherapy, and intraocular injections of
      chemotherapeutic agents were successfully introduced. CONCLUSIONS: Nearly all
      patients with retinoblastoma in developed countries can now be cured of their
      primary cancer--a remarkable achievement for a childhood cancer that once was
      uniformly fatal. Much of this success is owed to deciphering the role of the Rb
      gene, and the benefits of targeted therapies, such as chemoreduction with
      consolidation as well as intra-arterial and intravitreal chemotherapies. Going
      forward, the main challenge will be ensuring that access to care is available for
      all children, particularly those in developing countries.

PMID- 25065500
TI  - Real-time observation of liposome bursting induced by acetonitrile.
AB  - We show the bursting process of dioleoylphosphatidylcholine (DOPC) liposomes in
      response to the addition of acetonitrile, a small toxic molecule widely used in
      the fields of chemistry and industry. The percentage of destroyed liposomes is
      reduced upon decreasing the acetonitrile fraction in the aqueous solution and
      vesicle bursting is not observed at volume ratios of 4:6 and below. This
      indicates that a high fraction of acetonitrile causes the bursting of liposomes,
      and it is proposed that this occurs through insertion of the molecules into outer
      leaflet of the lipid bilayer. The elapsed time between initial addition of
      acetonitrile and liposome bursting at each vesicle is also measured and
      demonstrated to be dependent on the volume fraction of acetonitrile and the
      vesicle size. 

PMID- 25065499
TI  - Behavioral inhibition and developmental risk: a dual-processing perspective.
AB  - Behavioral inhibition (BI) is an early-appearing temperament characterized by
      strong reactions to novelty. BI shows a good deal of stability over childhood and
      significantly increases the risk for later diagnosis of social anxiety disorder
      (SAD). Despite these general patterns, many children with high BI do not go on to
      develop clinical, or even subclinical, anxiety problems. Therefore, understanding
      the cognitive and neural bases of individual differences in developmental risk
      and resilience is of great importance. The present review is focused on the
      relation of BI to two types of information processing: automatic (novelty
      detection, attention biases to threat, and incentive processing) and controlled
      (attention shifting and inhibitory control). We propose three hypothetical models
      (Top-Down Model of Control; Risk Potentiation Model of Control; and
      Overgeneralized Control Model) linking these processes to variability in
      developmental outcomes for BI children. We argue that early BI is associated with
      an early bias to quickly and preferentially process information associated with
      motivationally salient cues. When this bias is strong and stable across
      development, the risk for SAD is increased. Later in development, children with a
      history of BI tend to display normative levels of performance on controlled
      attention tasks, but they demonstrate exaggerated neural responses in order to do
      so, which may further potentiate risk for anxiety-related problems. We conclude
      by discussing the reviewed studies with reference to the hypothetical models and
      make suggestions regarding future research and implications for treatment. 

PMID- 25065501
TI  - Elucidation of kinetic mechanisms of human translesion DNA polymerase kappa using
      tryptophan mutants.
AB  - To investigate the conformational dynamics of human DNA polymerase kappa (hpol
      kappa), we generated two mutants, Y50W (N-clasp region) and Y408W (linker between
      the thumb and little finger domains), using a Trp-null mutant (W214Y/W392H) of
      the hpol kappa catalytic core enzyme. These mutants retained catalytic activity
      and similar patterns of selectivity for bypassing the DNA adduct 7,8-dihydro-8
      oxo-2'-deoxyguanosine, as indicated by the results of steady-state and pre-steady
      state kinetic experiments. Stopped-flow kinetic assays with hpol kappa Y50W and
      T408W revealed a decrease in Trp fluorescence with the template G:dCTP pair but
      not for any mispairs. This decrease in fluorescence was not rate-limiting and is
      considered to be related to a conformational change necessary for correct
      nucleotidyl transfer. When a free 3'-hydroxyl was present on the primer, the Trp
      fluorescence returned to the baseline level at a rate similar to the observed
      kcat , suggesting that this change occurs during or after nucleotidyl transfer.
      However, polymerization rates (kpol ) of extended-product formation were fast,
      indicating that the slow fluorescence step follows phosphodiester bond formation
      and is rate-limiting. Pyrophosphate formation and release were fast and are
      likely to precede the slower relaxation step. The available kinetic data were
      used to fit a simplified minimal model. The extracted rate constants confirmed
      that the conformational change after phosphodiester bond formation was rate
      limiting for hpol kappa catalysis with the template G:dCTP pair.

PMID- 25065502
TI  - Hypericin damages the ectatic capillaries in a Roman cockscomb model and inhibits
      the growth of human endothelial cells more potently than hematoporphyrin does
      through induction of apoptosis.
AB  - Hypericin (HY) is a promising photosensitizer (PS) for use in photodynamic
      therapy (PDT). Port-wine stains (PWSs) are congenital superficial dermal
      capillary malformations. In this study, we evaluated the photocytotoxic effects
      of HY for PDT in human vascular endothelial cells and a chicken cockscomb model.
      HY significantly inhibited the growth of human umbilical vein endothelial cells
      (HUVECs), as determined by colorimetric assays and morphological observation, and
      flow cytometry assays indicated induction of apoptosis and collapse of the
      mitochondrial membrane potential. In addition, HY more effectively inhibited
      growth of and induced apoptosis in HUVECs compared with hematoporphyrin (HP).
      Further experiments performed in a Roman chicken cockscomb model also showed a
      clear photocytotoxic effect on the cockscomb dermal capillary upon intravenous
      injection of HY. This effect may be due to the role of HY in the induction of
      apoptosis. Transmission electron microscopical analysis showed mitochondrial
      morphological changes such as incomplete ridges and swelling, and
      immunohistochemical assays showed an increase in the release of cytochrome c. In
      conclusion, HY exhibited a greater photocytotoxic activity than did HP toward the
      growth of endothelial cells and may thus represent a potent PS for PWS PDT. 

PMID- 25065503
TI  - Interictal psychosis following temporal lobe surgery: dentate gyrus pathology.
AB  - BACKGROUND: De novo interictal psychosis, albeit uncommon, can develop in
      patients following temporal lobe surgery for epilepsy. Pathological alterations
      of the dentate gyrus, including cytoarchitectural changes, immaturity and axonal
      reorganization that occur in epilepsy, may also underpin co-morbid psychiatric
      disorders. Our aim was to study candidate pathways that may be associated with
      the development of interictal psychosis post-operatively in patients with
      hippocampal sclerosis (HS). METHOD: A total of 11 patients with HS who developed
      interictal psychosis (HS-P) post-operatively were compared with a matched
      surgical HS group without psychosis (HS-NP). Resected tissues were investigated
      for the extent of granule cell dispersion, mossy fibre sprouting and calbindin
      expression in the granule cells. We quantified doublecortin, mini-chromosome
      maintenance protein 2 (MCM2) and reelin-expressing neuronal populations in the
      dentate gyrus as well as the distribution of cannabinoid type 1 receptor (CBR1).
      RESULTS: The patterns of neuronal loss and gliosis were similar in both groups.
      HS-P patients demonstrated less mossy fibre sprouting and granule cell dispersion
      (p < 0.01) and more frequent reduction in calbindin expression in granule cells.
      There were no group differences in the densities of immature MCM2, doublecortin
      and reelin-positive cells. CBR1 labelling was significantly lower in Cornu
      ammonis area CA4 relative to other subfields (p < 0.01); although reduced
      staining in all hippocampal regions was noted in HS-P compared with HS-NP
      patients, the differences were not statistically significant. CONCLUSIONS: The
      alterations in dentate gyrus pathology found in HS-P patients could indicate
      underlying differences in the cellular response to seizures. These mechanisms may
      predispose to the development of psychosis in epilepsy and warrant further
      investigation.

PMID- 25065504
TI  - The renal patient support group: supporting patients with chronic kidney disease
      through social media.
AB  - BACKGROUND: The Renal Patient Support Group (RPSG) is a voluntary Facebook group
      that was developed in 2009 in the UK. The RPSG now has in excess of 5000 members.
      OBJECTIVE: To highlight the work of the RPSG and to describe how the use of
      social media has helped raise awareness of chronic kidney disease (CKD). The RPSG
      offers online peer support internationally, with members sharing their
      experiences. METHODS: Since the RPSG is mainly a Facebook platform, this medium
      has lent itself to raising CKD awareness, also allowing group members to share
      real-life stories. CONCLUSION: The RPSG continues to expand and invites health
      professionals to gain opportunities provided by social media networks to improve
      the health of their patients by facilitating and getting involved in 'real'
      discussions.

PMID- 25065505
TI  - The extinction of the dinosaurs.
AB  - Non-avian dinosaurs went extinct 66 million years ago, geologically coincident
      with the impact of a large bolide (comet or asteroid) during an interval of
      massive volcanic eruptions and changes in temperature and sea level. There has
      long been fervent debate about how these events affected dinosaurs. We review a
      wealth of new data accumulated over the past two decades, provide updated and
      novel analyses of long-term dinosaur diversity trends during the latest
      Cretaceous, and discuss an emerging consensus on the extinction's tempo and
      causes. Little support exists for a global, long-term decline across non-avian
      dinosaur diversity prior to their extinction at the end of the Cretaceous.
      However, restructuring of latest Cretaceous dinosaur faunas in North America led
      to reduced diversity of large-bodied herbivores, perhaps making communities more
      susceptible to cascading extinctions. The abruptness of the dinosaur extinction
      suggests a key role for the bolide impact, although the coarseness of the fossil
      record makes testing the effects of Deccan volcanism difficult. 

PMID- 25065506
TI  - Woven structured triboelectric nanogenerator for wearable devices.
AB  - To date, quite a few wearable electronics have entered the market, which are
      changing the life pattern of consumers. However, the limited lifetime and energy
      storage capacity have made rechargeable batteries the bottleneck in wearable
      technology, especially with the increase of number of wearable devices and their
      large distribution. To solve this problem, we demonstrate a woven-structured
      triboelectric nanogenerator (W-TENG) using commodity nylon fabric, polyester
      fabric, and conductive silver fiber fabric. With the advantage of being flexible,
      washable, breathable, wearable, and able to be triggered by a freestanding
      triboelectric layer, this W-TENG can move freely without any constraint and is
      suitable for wearable electronics. To demonstrate the potential applications of
      the W-TENG, the W-TENG is integrated into shoes, coats, and trousers to harvest
      different kinds of mechanical energy from human motion. This work presents a new
      approach in applying triboelectric nanogenerator to wearable devices. 

PMID- 25065507
TI  - Lichenysin, a cyclooctapeptide occurring in Chinese liquor jiannanchun reduced
      the headspace concentration of phenolic off-flavors via hydrogen-bond
      interactions.
AB  - Nonvolatile compounds play important roles in the quality of alcoholic beverages.
      In our previous work, a type of cyclooctapeptide lichenysin was newly identified
      in Chinese strong-aroma type liquor. In this work, it was found that lichenysin
      could selectively affect aroma volatility in strong-aroma type (Jiannanchun)
      liquor. Interaction of lichenysin and volatile phenolic compounds (off-odors in
      strong-aroma type liquor) was characterized using headspace solid-phase
      microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC
      MS). HS-SPME results indicated that lichenysin very efficiently suppressed the
      volatility of phenolic compounds by 36-48% (P < 0.05). Thermodynamic analysis
      showed that the binding process was mainly mediated by hydrogen bonding.
      Furthermore, the mixture of lichenysin and 4-ethylguaiacol revealed
      intermolecular cross peaks between the aH (Val) of lichenysin and the 1H of 4
      ethylguaiacol, by using nuclear Overhauser effect spectroscopy. This study will
      help to further understand the interaction mechanisms between flavor and
      nonvolatile matrix components in Chinese liquors. 

PMID- 25065508
TI  - An assessment of Canadian systems for triaging referred out genetic testing.
AB  - The field of genetics is evolving rapidly, significantly expanding the number of
      clinically useful genetic tests. The cost of genetic testing has created an
      increasing burden on public health care budgets. In Canada, funding bodies have
      responded by developing independent systems. Key individuals in each province and
      territory participated in a semi-structured interview regarding the process in
      their jurisdiction to approve funding for referred out genetic testing and their
      decision-making criteria. Two themes were identified: the importance of clinical
      utility in decision-making and the utilization of genetic specialists as gate
      keepers. Allocation of a specific budget appears to be associated with some
      fiscal responsibility. Collaboration between provincial and territorial bodies
      may lead to a more unified approach across Canada. 

PMID- 25065509
TI  - UK and European Union public and charitable funding from 2008 to 2013 for
      bacteriology and antibiotic research in the UK: an observational study.
AB  - BACKGROUND: Since the 1990s, the number of new antibacterial drugs has plummeted
      and the number of antibiotic-resistant infections has risen, which has decreased
      the effective treatment of many disorders, including sepsis. We aimed to assess
      whether funding for bacteriology and antibiotic research to UK researchers had
      increased in response to this global crisis. METHODS: We systematically searched
      websites and databases of agencies that fund research in the UK to identify
      publicly and charitably funded projects from financial years 2008 to 2013 within
      the specialties of bacteriology and antibiotic research. We created a database to
      identify the projects funded. Grants awarded in euros were converted to pounds
      sterling (?1=L0.86). FINDINGS: We identified 609 projects within the specialty of
      bacteriology, 196 (32.2%) of which were on antibiotics. Of L13 846.1 million of
      available research funding, L269.2 million (1.9%) was awarded to bacteriology
      projects and L95.0 million (0.7%) was awarded for research on antibiotics.
      Additionally, L181.4 million in European Union (EU) funding was awarded to
      antibiotic research consortia including researchers based within the UK,
      including two EU Innovative Medicines Initiative awards, totalling L85.2 million.
      INTERPRETATION: To increase awareness of who funds antibiotic research and to
      facilitate priority setting and funding decisions, funding organisations need to
      be aware of the breadth and depth of present funding as a baseline by which
      funding from 2014 onwards can be measured and so that informed decisions about
      the future level of funding can be made. To resolve the crisis of antibiotic
      resistance, present levels of funding are inadequate and should be increased
      substantially. FUNDING: British Society for Antimicrobial Chemotherapy.

PMID- 25065510
TI  - Gross underinvestment in antibacterial research.

PMID- 25065511
TI  - Incorporation of gold-coated microspheres into embryoid body of human embryonic
      stem cells for cardiomyogenic differentiation.
AB  - Human embryonic stem cells (hESCs) are a useful cell source for cardiac
      regeneration by stem cell therapy. In this study, we show that incorporation of
      gold-coated microspheres into hESC-derived embryoid bodies (EBs) enhances the
      cardiomyogenic differentiation process of pluripotent embryonic stem cells. A
      polycaprolactone (PCL) microsphere surface was coated with gold. Either gold
      coated PCL microspheres (AuMS) or PCL microspheres (MS) were incorporated into
      hESC-derived EBs. AuMS and MS were not cytotoxic. AuMS promoted the expression of
      genes for mesodermal and cardiac mesodermal lineage cells, both of which are
      intermediates in the process of cardiac differentiation of hESCs on day 4 and the
      expression of cardiomyogenic differentiation markers on day 14 compared to MS.
      AuMS also enhanced gene expression of cardiac-specific extracellular matrices.
      Incorporation of gold-coated MS into hESC-derived EBs may provide a new platform
      for inducing cardiomyogenic differentiation of pluripotent embryonic stem cells. 

PMID- 25065512
TI  - Potential impact of macroclimatic variability on the epidemiology of giardiasis
      in three provinces of Cuba, 2010-2012.
AB  - Climate change and variability are common phenomena affecting various infectious
      diseases. Many studies have been performed on vector-borne diseases; however, few
      studies have addressed such influences on intestinal parasitic diseases (e.g.,
      giardiasis). In this study, using nonlinear Poisson regression models, we
      assessed the potential associations between macroclimatic variation and
      giardiasis cases in children and school workers from three provinces of Cuba in
      the context of large sampling and parasitological assessment. Between 2010 and
      2012, 293,019 subjects were assessed, resulting in 6357 positive for Giardia
      (216.95 cases/10,000 pop.; 95%CI 211.7-222.2). The variation in time for those
      giardiasis rates ranged from 35.8 to 525.8 cases/10,000 pop. Nonlinear Poisson
      regression models between the ONI index and the giardiasis incidence indicated a
      significant association (p<0.01). With lower values of ONI, lower incidence of
      giardiasis was observed at Havana (pseudo r(2)=0.0576; p<0.001) and Guantanamo
      (pseudo r(2)=0.0376; p<0.001). Although these results are preliminary and the
      magnitude of association is not higher, the results were of statistical
      significance. This result indicates the need to assess in detail in further
      studies the impact of additional macroclimatic and microclimatic variables on the
      epidemiology of this still important intestinal parasitic disease, not only in
      Cuba but also in other countries of the Caribbean and Latin American region.

PMID- 25065514
TI  - The North wind doth blow....

PMID- 25065513
TI  - Clinical outcomes of hepatitis B virus coinfection in a United States cohort of
      hepatitis C virus-infected patients.
AB  - The effect of hepatitis B virus (HBV) coinfection in patients with hepatitis C
      virus (HCV) remains unclear. We used the National Veterans Affairs HCV Clinical
      Case Registry to identify patients with confirmed HCV viremia during 1997-2005.
      We defined HBV coinfection as a positive test for hepatitis B surface antigen,
      HBV DNA, or hepatitis B e antigen. We defined cirrhosis and hepatocellular
      carcinoma (HCC) based on the validated ICD-9 codes and determined mortality
      through the end of 2009. We performed Cox proportional hazard regression analyses
      to examine the effect of HBV coinfection stratified by HBV DNA status (positive
      or negative) on the risk of cirrhosis, HCC, and death adjusting for patients'
      age, gender, race, human immunodeficiency virus (HIV) infection, alcohol or drug
      use, Deyo Score, and antiviral treatment. Among 99,548 patients with HCV
      infection, 1,370 patients (1.4%) had HBV coinfection. Of the coinfected patients,
      677 (49.4%) patients had at least one HBV DNA test done and 303 patients (44.7%)
      tested positive for HBV DNA. The incidence rates of cirrhosis, HCC, and death
      were significantly higher in patients with HBV coinfection and detectable HBV DNA
      compared to HCV monoinfection (36.8, 6.9, and 41.7 versus 17.4, 3.6, and 31.4 per
      1,000 person-years, respectively; P < 0.05 for all comparisons). After adjustment
      for demographic, clinical, and treatment factors, patients with detectable HBV
      DNA had a significantly higher risk for cirrhosis (hazard ratio [HR] = 1.89 95%
      confidence interval [CI] = 1.46-2.45), HCC (HR = 2.12, 95% CI = 1.26-3.60), and
      death (HR = 1.62, 95% CI = 1.33-1.99) compared to HCV monoinfected patients.
      There were no differences in the risk of cirrhosis, HCC, or overall mortality
      between coinfected patients with undetectable HBV DNA and those with HCV
      monoinfection (HR = 1.18, 95% CI = 0.90-1.55; 1.54, 95% CI = 0.93-2.56; 1.08, 95%
      CI = 0.88-1.33, respectively). CONCLUSION: We found that while only a small
      number of HCV patients were coinfected with HBV, patients with documented HBV
      viremia were at a significantly higher risk for cirrhosis, HCC, and overall death
      than HCV monoinfected patients. Absence of HBV replication was associated with a
      clinical course similar to that of HCV monoinfected patients.

PMID- 25065515
TI  - The impacts of injury at the individual, community and societal levels: a
      systematic meta-review.
AB  - OBJECTIVES: Injury is a major public health problem. While the impacts of injury
      on the injured person are well documented, there is relatively little knowledge
      about the impacts of injury on those individuals and groups in the community
      connected to the injured person. This study seeks to describe this breadth of
      research using a meta-review methodology. STUDY DESIGN: Systematic meta-review.
      METHODS: To gain a better understanding of the known impacts of injury on family,
      community and society, a systematic meta-review of injury outcomes research
      literature was conducted. Seventy-eight peer-reviewed published literature
      reviews were included in the meta-review. RESULTS: Of these, 70 reported outcomes
      at the level of the injured person including mortality, body functions, activity
      and participation limitations. Nine reviews reported impacts at the level of the
      community including impacts on family members, work colleagues and carers. Six
      studies reported impacts at the societal level including economic, health system
      and injury compensation system impacts. CONCLUSIONS: In summary, the meta-review
      identified a substantial body of knowledge at the individual level outcomes of
      injury, and a relative lack of information regarding the community and societal
      impacts of injury. An injury outcome framework is proposed on the basis of the
      findings of the meta-review to guide future research activity, particularly with
      regard to injury outcome domains where there is currently limited evidence. A
      comprehensive framework that takes account of all levels of impact is necessary
      for effective policies, systems and strategies to support recovery following
      injury.

PMID- 25065516
TI  - The Cold Weather Plan evaluation: an example of pragmatic evidence-based policy
      making?
AB  - OBJECTIVES: An evaluation of the Cold Weather Plan (CWP) for England 2011-2012
      was undertaken in April 2012 to generate the basis for further revisions. It is
      widely considered good practice to formulate and revise policy on the basis of
      the best available evidence. This paper examines whether the evaluation is an
      example of pragmatic evidence-based policy-making. STUDY DESIGN: A process
      evaluation with a formative multimethods approach. METHODS: An electronic survey
      and national workshop were conducted alongside the production of a number of
      summary reports from the Health Protection Agency surveillance systems and Met
      Office meteorological data. The Department of Health and the Met Office were
      consulted on how the evaluation recommendations shaped the revised CWP and Met
      Office Cold Weather Alerting System respectively. RESULTS: The Cold Weather Plan
      survey had 442 responses, a majority from Local Authorities, and from all regions
      of England. Thematic analysis generated qualitative data, which along with
      feedback from the workshop were synthesized into six main recommendations.
      Reviewing the new CWP and the Met Office Cold Weather Alerting System revealed
      significant modifications on the basis of the evaluation. CONCLUSIONS: The
      evaluation sets the context for cold weather and health during the 2011-2012
      winter. This study shows that the CWP 2012-2013 was revised on the basis of the
      national evaluation recommendations and is an example of pragmatic evidence-based
      policy-making.

PMID- 25065517
TI  - Using an Emergency Department Syndromic Surveillance System to investigate the
      impact of extreme cold weather events.
AB  - This report describes the development of novel syndromic cold weather public
      health surveillance indicators for use in monitoring the impact of extreme cold
      weather on attendances at EDs, using data from the 2010-11 and 2011-12 winters. A
      number of new surveillance indicators were created specifically for the
      identification and monitoring of cold weather related ED attendances, using the
      diagnosis codes provided for each attendance in the Emergency Department
      Syndromic Surveillance System (EDSSS), the first national syndromic surveillance
      system of its kind in the UK. Using daily weather data for the local area, a time
      series analysis to test the sensitivity of each indicator to cold weather was
      undertaken. Diagnosis codes relating to a health outcome with a potential direct
      link to cold weather were identified and assigned to a number of 'cold weather
      surveillance indicators'. The time series analyses indicated strong correlations
      between low temperatures and cold indicators in nearly every case. The strongest
      fit with temperature was cold related fractures in females, and that of snowfall
      was cold related fractures in both sexes. Though currently limited to a small
      number of sentinel EDs, the EDSSS has the ability to give near real-time detail
      on the magnitude of the impact of weather events. EDSSS cold weather surveillance
      fits well with the aims of the Cold Weather Plan for England, providing
      information on those particularly vulnerable to cold related health outcomes
      severe enough to require emergency care. This timely information aids those
      responding to and managing the effects on human health, both within the EDs
      themselves and in the community as a whole. 

PMID- 25065518
TI  - Pregnant immigrant Nigerian women: an exploration of dietary intakes.
AB  - OBJECTIVE: The aim of the study is to explore the dietary intakes of a prominent
      ethnic minority group of women from Sub-Saharan Africa during pregnancy, in order
      to identify nutritional issues of concern which may impact on pregnancy outcomes
      and whether different food based dietary guidelines may be required to meet their
      needs. STUDY DESIGN: This is an observational study with quantitative assessment
      of nutrient intakes and an exploration of meal composition and food choices.
      METHODS: Fifty-two Nigerian pregnant women in their second or third trimester of
      pregnancy were recruited from antenatal clinics in the National Maternity
      Hospital, Dublin, Ireland. Early pregnancy weight was measured and body mass
      index recorded. A 24 h dietary recall was used to assess food and nutrient
      intakes. RESULTS: Eighty-nine per cent of the study population were classified as
      overweight or obese. These women appear to be maintaining traditional African
      dietary habits and have a healthy macronutrient composition in the diet. The
      intake of key pregnancy micronutrients such as calcium, vitamin D and folate may
      be insufficient from diet alone to meet requirements and supplements may be
      inadequately utilized in a timely manner. CONCLUSIONS: These women represent a
      vulnerable obstetric group that may be at risk of adverse pregnancy outcomes due
      to high obesity rates and inadequate micronutrient status in early pregnancy.
      Provision of dietary advice should be tailored to suit their cultural dietary
      practices and food preferences. Pre-conception counselling on healthy lifestyle
      and appropriate supplement usage may be beneficial, although larger studies are
      required to assess the need for specific nutrition policy recommendations.

PMID- 25065519
TI  - 'It's effective but should I bother?' A study of personal protection measures
      against Malaria in urban India.
AB  - OBJECTIVES: Malaria affects millions of people in urban and rural India every
      year. This study addresses two main gaps in current research: 1) attitudes
      towards personal protective strategies against Malaria among urban populations;
      and 2) understanding of the extent to which urban health information seeking
      preferences shape preventive behaviours. STUDY DESIGN: Cross-sectional face-to
      face surveys using stratified sampling design. METHODS: A 60-min survey was
      carried out to 1000 middle-of-pyramid (MOP) population in five main cities in
      India by trained interviewers. Variables assessed included perceived
      effectiveness and actual practice of 14 scientific and indigenous personal
      protection methods, Malaria-related attitudes (susceptibility, severity and
      response efficacy) and health information seeking preferences. RESULTS: Actual
      practice of Malaria preventive behaviours was found to be significantly lower
      than the perceived effectiveness of each of the fourteen scientific and
      indigenous methods. Television, newspapers, and mobile phones were reported as
      the top three preferred media for seeking public health information. Lastly,
      perceived susceptibility, response efficacy, and health-related media use were
      found to play significant roles in predicting actual practice behaviours.
      CONCLUSIONS: Our study highlights a need for health authorities to focus on
      translating positive attitudes to actual practice of preventive behaviours.
      Communication efforts may focus on the use of TV, newspapers and mobile phones
      for greater reach and efficacy. Other implications for Malaria prevention
      programs are discussed.

PMID- 25065520
TI  - Elevated teenage conception risk amongst looked after children; a national audit.

PMID- 25065521
TI  - The index of 'well-being': a clue for public health?

PMID- 25065522
TI  - Response to Dr Alain Braillon.

PMID- 25065523
TI  - Oral fibrous histiocytoma-associated calcification.

PMID- 25065524
TI  - pH-dominated niche segregation of ammonia-oxidising microorganisms in Chinese
      agricultural soils.
AB  - Ammonia-oxidising archaea (AOA) are increasingly recognised as the primary
      mediators of soil ammonia oxidation, particularly in acidic soils. To explore the
      niche segregation of AOA and ammonia-oxidising bacteria (AOB) and the potential
      effect of this segregation on nitrification rates and the nitrogen cycle in
      Chinese agricultural soils, AOA and AOB amoA gene databases were established, and
      454 high-throughput sequencing was used to investigate the key factors leading to
      the niche segregation of these two types of microorganisms. qPCR results
      demonstrated that there were more functional genes for AOA than for AOB in most
      of the soils. AOA diversity was higher than AOB diversity in most of the soils
      with AOA operational taxonomic units (OTU) numbers ranging from 40 to 169 and AOB
      OTU numbers ranging from 18 to 105. pH was the most important factor influencing
      the community structure of AOA (P < 0.01) and AOB (P < 0.05), and acidophilic AOA
      (i.e. Nitrosotalea-related sequences) were dominant in soils with pH values below
      6.0. In addition, AOA amoA gene copy numbers were significantly positively
      correlated with pH (P < 0.05), the ratio of AOA OTU numbers/AOB OTU numbers was
      significantly negatively correlated with pH (P < 0.05), and the percentage of
      sequences represented by the Nitrosotalea cluster was significantly negatively
      correlated with pH (P < 0.01).

PMID- 25065525
TI  - The Chiari malformations: a review with emphasis on anatomical traits.
AB  - Hindbrain herniations come in many forms and have been further subdivided as
      their original descriptions. For cerebellar tonsillar ectopia, they can be
      divided into two categories, acquired and congenital. Acquired hindbrain
      herniations are due to increased intracranial pressure caused by certain
      conditions such as trauma or brain tumor. Although the mechanism for their
      formation is not clear, congenital hindbrain herniation makes up the majority of
      these congenital malformations. Furthermore, these malformations are often found
      to harbor additional anatomical derailments in addition to the hindbrain
      herniation whether it be the cerebellar tonsils (Chiari I malformation) or the
      cerebellar vermis (Chiari II malformation). This article reviews these forms of
      cerebellar ectopia and describes the details of their anomalous anatomy.
      Moreover, this article compares and contrasts the differing embryological
      theories found in this literature.

PMID- 25065526
TI  - Long-term follow-up after tissue-engineered buccal mucosa urethroplasty.

PMID- 25065527
TI  - Re: Walter Artibani, Vincenzo Ficarra, Ben J. Challacombe, et al. EAU policy on
      live surgery events. Eur urol 2014;66:87-97.

PMID- 25065529
TI  - The dystonias: a heterogeneous collection.

PMID- 25065528
TI  - Personalized drug combinations to overcome trastuzumab resistance in HER2
      positive breast cancer.
AB  - HER2-positive (HER2+) breast cancer accounts for 18%-20% of all breast cancer
      cases and has the second poorest prognosis among breast cancer subtypes.
      Trastuzumab, the first Food and Drug Administration-approved targeted therapy for
      breast cancer, established the era of personalized treatment for HER2+ metastatic
      disease. It is well tolerated and improves overall survival and time-to-disease
      progression; with chemotherapy, it is part of the standard of care for patients
      with HER2+ metastatic disease. However, many patients do not benefit from it
      because of resistance. Substantial research has been performed to understand the
      mechanism of trastuzumab resistance and develop combination strategies to
      overcome the resistance. In this review, we provide insight into the current
      pipeline of drugs used in combination with trastuzumab and the degree to which
      these combinations have been evaluated, especially in patients who have
      experienced disease progression on trastuzumab. We conclude with a discussion of
      the current challenges and future therapeutic approaches to trastuzumab-based
      combination therapy. 

PMID- 25065530
TI  - Probing the coagulation pathway with aptamers identifies combinations that
      synergistically inhibit blood clot formation.
AB  - Coordinated enzymatic reactions regulate blood clot generation. To explore the
      contributions of various coagulation enzymes in this process, we utilized a panel
      of aptamers against factors VIIa, IXa, Xa, and prothrombin. Each aptamer dose
      dependently inhibited clot formation, yet none was able to completely impede this
      process in highly procoagulant settings. However, several combinations of two
      aptamers synergistically impaired clot formation. One extremely potent aptamer
      combination was able to maintain human blood fluidity even during extracorporeal
      circulation, a highly procoagulant setting encountered during cardiopulmonary
      bypass surgery. Moreover, this aptamer cocktail could be rapidly reversed with
      antidotes to restore normal hemostasis, indicating that even highly potent
      aptamer combinations can be rapidly controlled. These studies highlight the
      potential utility of using sets of aptamers to probe the functions of proteins in
      molecular pathways for research and therapeutic ends. 

PMID- 25065532
TI  - Synthesis of a phosphoantigen prodrug that potently activates Vgamma9Vdelta2 T
      lymphocytes.
AB  - Phosphoantigen-sensitive Vgamma9Vdelta2 T cells are important responders to
      infections and malignancy. However, the mechanisms by which phosphoantigens
      stimulate Vgamma9Vdelta2 T cells are unclear. Here, we synthesized phosphoantigen
      prodrugs and used them to demonstrate that intracellular delivery of
      phosphoantigens is required for their activity. The pivaloyloxymethyl prodrug is
      the most potent phosphoantigen described to date, with stronger stimulation of
      Vgamma9Vdelta2 T cells from human peripheral blood and greater ability to induce
      lysis of Daudi lymphoma cells relative to the previously most potent compound,
      (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP). We demonstrate high
      binding affinity between phosphoantigens and the intracellular region of
      butyrophilin 3A1 (BTN3A1), localized to the PRY/SPRY (B30.2) domain, but also
      affecting the membrane proximal region. Our findings promote a phosphoantigen
      prodrug approach for cancer immunotherapy and unravel fundamental aspects of the
      mechanisms of Vgamma9Vdelta2 T cell activation. 

PMID- 25065531
TI  - Anti-inflammatory actions of acanthoic acid-related diterpenes involve activation
      of the PI3K p110gamma/delta subunits and inhibition of NF-kappaB.
AB  - The effect of acanthoic acid analogs on the response to proinflammatory challenge
      was investigated. Some pimarane diterpenes are known activators of the
      LXRalphabeta nuclear receptors, but we show here that they also exert a rapid,
      potent, and selective activation of the p110gamma and p110delta subunits of PI3K.
      Combination of these effects results in an important attenuation of the global
      transcriptional response to LPS in macrophages. PI3K/Akt activation leads to
      inhibition of the LPS-dependent stimulation of IKK/NF-kappaB and p38 and ERK
      MAPKs. Macrophages from LXRalphabeta-deficient mice exhibited an inhibition of
      these pathways similar to the corresponding wild-type cells. Silencing or
      inhibition of p110gamma/delta suppressed the effect of these diterpenes (DTPs) on
      IKK/NF-kappaB and MAPKs signaling. Taken together, these data show a multitarget
      anti-inflammatory mechanism by these DTPs including a selective activation of
      PI3K isoenzymes. 

PMID- 25065533
TI  - eSNaPD: a versatile, web-based bioinformatics platform for surveying and mining
      natural product biosynthetic diversity from metagenomes.
AB  - Environmental Surveyor of Natural Product Diversity (eSNaPD) is a web-based
      bioinformatics and data aggregation platform that aids in the discovery of gene
      clusters encoding both novel natural products and new congeners of medicinally
      relevant natural products using (meta)genomic sequence data. Using PCR-generated
      sequence tags, the eSNaPD data-analysis pipeline profiles biosynthetic diversity
      hidden within (meta)genomes by comparing sequence tags to a reference data set of
      characterized gene clusters. Sample mapping, molecule discovery, library mapping,
      and new clade visualization modules facilitate the interrogation of large
      (meta)genomic sequence data sets for diverse downstream analyses, including, but
      not limited to, the identification of environments rich in untapped biosynthetic
      diversity, targeted molecule discovery efforts, and chemical ecology studies.
      eSNaPD is designed to generate a global atlas of biosynthetic diversity that can
      facilitate a systematic, sequence-based interrogation of nature's biosynthetic
      potential. 

PMID- 25065534
TI  - Psychosocial factors related to smoking: the midlife study.
AB  - BACKGROUND: There is limited research on the correlates of cigarette smoking in
      women in late midlife. OBJECTIVES: The present study examined the associations
      between risk factors in several psychosocial domains and current cigarette
      smoking among women in their mid-60s. These domains included risks in personal
      attributes, family relationships, negative life events, financial stressors,
      contextual factors, and problematic alcohol use. METHODS: Data were from a cohort
      of women originally living in two upstate New York counties (N = 511) in late
      midlife (mean age = 65). Bivariate and multivariate logistic regression analyses
      were conducted. RESULTS: The results supported our hypotheses. The cumulative
      psychosocial risk index was significantly associated with a greater likelihood of
      cigarette smoking [A.O.R. = 1.53; 95% C.I. (1.3-.181); p < .001] after
      controlling for age and educational level. CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: It is important to reduce the number of psychosocial risk factors
      faced by women in their 60s in order to reduce the likelihood of continued
      cigarette smoking.

PMID- 25065535
TI  - A phase-specific psychological therapy for people with problematic cannabis use
      following a first episode of psychosis: a randomized controlled trial.
AB  - BACKGROUND: Cannabis use is high amongst young people who have recently had their
      first episode of psychosis, and is associated with worse outcomes. To date,
      interventions to reduce cannabis consumption have been largely ineffective, and
      it has been suggested that longer treatment periods are required. METHOD: In a
      pragmatic single-blind randomized controlled trial 110 participants were randomly
      allocated to one of three conditions: a brief motivational interviewing and
      cognitive behavioural therapy (MI-CBT) intervention (up to 12 sessions over 4.5
      months) with standard care from an early intervention service; a long MI-CBT
      intervention (up to 24 sessions over 9 months) with standard care; or standard
      care alone. The primary outcome was change in cannabis use as measured by
      Timeline Followback. RESULTS: Neither the extended nor the brief interventions
      conferred benefit over standard care in terms of reductions in frequency or
      amount of cannabis use. Also the interventions did not result in improvements in
      the assessed clinical outcomes, including symptoms, functioning, hospital
      admissions or relapse. CONCLUSIONS: Integrated MI and CBT for people with
      cannabis use and recent-onset psychosis does not reduce cannabis use or improve
      clinical outcomes. These findings are consistent with those in the published
      literature, and additionally demonstrate that offering a more extended
      intervention does not confer any advantage. Many participants were not at an
      action stage for change and for those not ready to reduce or quit cannabis,
      targeting associated problems rather than the cannabis use per se may be the best
      current strategy for mental health services to adopt.

PMID- 25065536
TI  - Length of stay and economic consequences with rivaroxaban vs enoxaparin/vitamin K
      antagonist in patients with DVT and PE: findings from the North American EINSTEIN
      clinical trial program.
AB  - OBJECTIVE: Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary
      embolism [(PE]) represents a substantial economic burden to the healthcare
      system. Using data from the randomized EINSTEIN DVT and PE trials, this North
      American sub-group analysis investigated the potential of rivaroxaban to reduce
      the length of initial hospitalization in patients with acute symptomatic DVT or
      PE. METHODS: A post-hoc analysis of hospitalization and length-of-stay (LOS) data
      was conducted in the North American sub-set of patients from the randomized, open
      label EINSTEIN trial program. Patients received either rivaroxaban (15 mg twice
      daily for 3 weeks followed by 20 mg once daily; n = 405) or dose-adjusted
      subcutaneous enoxaparin overlapping with (guideline-recommended 'bridging'
      therapy) and followed by a vitamin K antagonist (VKA) (international normalized
      ratio = 2.0-3.0; n = 401). The open-label study design allowed for the comparison
      of LOS between treatment arms under conditions reflecting normal clinical
      practice. LOS was evaluated using investigator records of dates of admission and
      discharge. Analyses were carried out in the intention-to-treat population using
      parametric tests. Costs were applied to the LOS based on weighted mean cost per
      day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization
      Project dataset. RESULTS: Of 382 patients hospitalized, 321 (84%), had acute
      symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE
      patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment
      groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE
      patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median
      = 1 day) compared with enoxaparin/VKA (mean = 4.5 vs 6.1; median = 3 vs 4),
      translating to total costs that were $3419 lower in rivaroxaban-treated patients.
      CONCLUSION: In hospitalized North American patients with VTE, treatment with
      rivaroxaban produced a statistically significant reduction in LOS. When treating
      DVT and PE patients, clinicians should consider newer anti-coagulants with less
      complex treatment regimens.

PMID- 25065537
TI  - Proximal gap-plasmon nanoresonators in the limit of vanishing inter-cavity
      separation.
AB  - Nanostructured metal-insulator-metal (MIM) metasurfaces supporting gap-plasmons
      (GPs) show great promise due to their ability to manipulate or concentrate light
      at the nanoscale, which is of importance to a broad palette of technologies. The
      interaction between individual, proximal GP nanoresonators, reaching the point of
      first electrical connection, can have unexpected, important consequences and
      remains unexplored. Here we study the optical properties of a GP-metasurface in
      the limit of diminishing spacing between GP nanocavities and show that it
      maintains its nanoresonator array character, with negligible GP interaction, even
      at extremely close proximity between cavities. Then, at the point where inter
      cavity electrical connection is first established, the surface abruptly
      transforms into a patterned metal-insulator-metal waveguide. We report detailed
      experimental evidence and explain the underlying physics through computational
      modeling and based on the properties and inherent symmetries of the
      electromagnetic field of the investigated metasurface. The novel phenomenon
      explored here can have a host of potential applications in the field of active
      plasmonic metamaterials, plasmonic photocatalysis and ultra-sensitive sensors. 

PMID- 25065538
TI  - Recovery post ICU.
AB  - Many ICU patients struggle to recovery following critical illness and may be left
      with physical, cognitive and psychological problems, which have a negative impact
      on their quality of life. Gross muscle mass loss and weakness can take some
      months to recover after the patients' Intensive Care Unit (ICU) discharge, in
      addition critical illness polyneuropathies can further complicate physical
      recovery. Psychological problems such as anxiety, depression and post traumatic
      stress disorder (PTSD) are common and have an negative impact on the patients'
      ability to engage in rehabilitation after ICU discharge. Finally cognitive
      deficit affecting memory can be a significant problem. The first step in helping
      patients to recover from such a devastating illness is to recognise those who
      have the greatest need and target interventions. Research now suggests that there
      are interventions that can accelerate physical recovery and reduce the incidence
      of psychological problems such as anxiety, depression and PTSD. Cognitive
      rehabilitation, however, is still in its infancy. This review will look at the
      research into patients' recovery and what can be done to improve this where
      needed. 

PMID- 25065540
TI  - Comparison of the effects of pulmonary rehabilitation with chest physical therapy
      on the levels of fibrinogen and albumin in patients with lung cancer awaiting
      lung resection: a randomized clinical trial.
AB  - BACKGROUND: Systemic inflammation plays an important role in the initiation,
      promotion, and progression of lung carcinogenesis. In patients with non-small
      cell lung cancer (NSCLC), fibrinogen levels correlate with neoplasia. Here we
      compared the effects of pulmonary rehabilitation (PR) with chest physical therapy
      (CPT) on fibrinogen and albumin levels in patients with LC and previous
      inflammatory lung disease awaiting lung resection. METHODS: We conducted a
      randomized clinical trial with 24 patients who were randomly assigned to
      Pulmonary Rehabilitation (PR) and Chest Physical Therapy (CPT) groups. Each group
      underwent training 5 days weekly for 4 weeks. All patients were assessed before
      and after four weeks of training through clinical assessment, measurement of
      fibrinogen and albumin levels, spirometry, 6-minute Walk Test (6MWT), quality of
      life survey, and anxiety and depression scale. PR involved strength and endurance
      training, and CPT involved lung expansion techniques. Both groups attended
      educational classes. RESULTS: A mixed between-within subjects analysis of
      variance (ANOVA) revealed a significant interaction between time (before and
      after intervention) and group (PR vs. CPT) on fibrinogen levels (F(1, 22)=0.57,
      p<0.0001) and a significant main effect of time (F(1, 22)=0.68, p=0.004). Changes
      in albumin levels were not statistically significant relative to the interaction
      effect between time and group (F(1, 22)=0.96, p=0.37) nor the main effects of
      time (F(1, 22)=1.00, p=1.00) and group (F(1, 22 )=0.59, p=0.45). A mixed between
      within subjects ANOVA revealed significant interaction effects between time and
      group for the peak work rate of the unsupported upper limb exercise (F(1,
      22)=0.77, p=0.02), endurance time (F(1, 22)=0.60, p=0.001), levels of anxiety
      (F(1, 22)=0.60, p=0.002) and depression (F(1, 22)=0.74, p=0.02), and the SF-36
      physical component summary (F(1, 22)=0.83, p=0.07). CONCLUSION: PR reduced serum
      fibrinogen levels, improved functional parameters, and quality of life of
      patients with LC and inflammatory lung disease awaiting lung resection. TRIAL
      REGISTRATION: Current Controlled Trials RBR-3nm5bv.

PMID- 25065541
TI  - Telemetry video-electroencephalography (EEG) in rats, dogs and non-human
      primates: methods in follow-up safety pharmacology seizure liability assessments.
AB  - INTRODUCTION: Non-clinical seizure liability studies typically aim to: 1) confirm
      the nature of EEG activity during abnormal clinical signs, 2) identify
      premonitory clinical signs, 3) measure plasma levels at seizure onset, 4)
      demonstrate that drug-induced seizures are self-limiting, 5) confirm that
      conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm
      the no observed adverse effect level (NOAEL) at EEG. Our aim was to originally
      characterize several of these items in a three species comparative study.
      METHODS: Cynomolgus monkey, Beagle dog and Sprague-Dawley rat with EEG telemetry
      transmitters were used to obtain EEG using the 10-20 system. Pentylenetetrazol
      (PTZ) was used to determine seizure threshold or as a positive seizurogenic
      agent. Clinical signs were recorded and premonitory signs were evaluated. In
      complement, other pharmacological agents were used to illustrate various safety
      testing strategies. RESULTS: Intravenous PTZ doses required to induce clonic
      convulsions were 36.1 (3.8), 56.1 (12.7) and 49.4 (11.7) mg/kg, in Beagle dogs,
      cynomolgus monkeys and Sprague-Dawley rats, respectively. Premonitory clinical
      signs typically included decreased physical activity, enhanced physiological
      tremors, hypersalivation, ataxia, emesis (except in rats) and myoclonus. In
      Sprague-Dawley rats, amphetamine (PO) increased high (approximately 40-120Hz),
      and decreased low (1-14Hz) frequencies. In cynomolgus monkeys, caffeine (IM)
      increased power in high (14-127Hz), and attenuated power in low (1-13Hz)
      frequencies. In the rat PTZ infusion seizure threshold model, yohimbine (SC and
      IV) and phenobarbital (IP) confirmed to be reliable positive controls as pro- and
      anticonvulsants, respectively. DISCUSSION: Telemetry video-EEG for seizure
      liability investigations was characterized in three species. Rats represent a
      first-line model in seizure liability assessments. Beagle dogs are often
      associated with overt susceptibility to seizure and are typically used in seizure
      liability studies only if required by regulators. Non-human primates represent an
      important model in seizure liability assessments given similarities to humans and
      a high translational potential.

PMID- 25065542
TI  - Radiation dose during coronary angiogram: relation to body mass index.
AB  - OBJECTIVE: Ionising radiation based diagnostic and therapeutic cardiology and
      radiology procedures are very common in present day medical practice and are one
      of the largest medical sources of radiation to humans. The risk to health from
      radiation has been extensively documented. Obesity is becoming epidemic not only
      in the western world, but also in developing countries. In the present study we
      investigated if a patient's Body Mass Index (BMI) has an effect on the radiation
      dose received by the patient and operator during diagnostic coronary angiography
      (CAG). METHODS: We analysed data of 3678 consecutive patients who underwent CAG
      from September 2007 to April 2010 in our cardiac catheter laboratory. Trans
      radial access was used in 622 patients, whereas 3056 patients underwent CAG
      through trans-femoral route. We calculated the radiation dose in dose area
      product (DAP) units and correlated it with body mass index, screening time,
      procedure time, contrast volume, vascular access route and individual operator.
      RESULTS: Among the explored parameters, body mass index had the most significant
      association with the radiation dose during the procedure. Despite having similar
      procedure times and contrast doses, patients with increased BMI received much
      higher radiation dose during CAG. We also found the left anterior oblique (LAO)
      caudal and LAO cranial views produced the biggest increase in radiation dose in
      patients with a high BMI. There was no inter-operator variability. CONCLUSION:
      Obese patients require more than double the radiation dose in comparison to those
      with normal BMI. The operator should be aware of the increased dose of radiation
      required when performing CAG in patients with increased BMI, and especially in
      LAO cranial and caudal views.

PMID- 25065543
TI  - Can patients be accurately assessed for familial hypercholesterolaemia in primary
      care?
AB  - OBJECTIVE: Familial Hypercholesterolaemia (FH) is the most prevalent monogenic
      condition causing premature coronary artery disease, although the majority of
      individuals remain undiagnosed. We sought to investigate whether individuals with
      FH could be accurately identified in primary care. METHODS: The Dutch Lipid
      Clinic Network Criteria scores (DLCNCS) assessed by general practitioners (GPs)
      were compared with DLCNCS assessed by specialists using primary care data in 153
      individuals. Thirty individuals with DLCNCS >=4 underwent specialist review and
      genetic testing. Clinical FH was defined as DLCNCS >=6, encompassing the probable
      and definite FH categories. RESULTS: GPs correctly classified 39 (86.7%)
      individuals with 'clinical FH', and 32 (94%) with 'unlikely FH' relative to
      specialists. Lin's concordance correlation coefficient was high (0.832 (0.783 -
      0.881), p< 0.001) between specialist and GPs, with an overall agreement of 83.6%,
      kappa 0.744 (0.642 - 0.831). After specialist review, 15 individuals (50%) were
      diagnosed with clinical FH, four (26.7%) had FH mutations. GPs correctly
      classified 12 (80%) of these individuals with clinical FH. CONCLUSION: GPs can
      accurately identify individuals at high and low risk of FH using the DLCNCS,
      which may augment opportunistic FH detection in the community. Increased
      education may enhance the diagnostic accuracy of FH in primary care.

PMID- 25065544
TI  - Protein kinase B (AKT1) genotype mediates sensitivity to cannabis-induced
      impairments in psychomotor control.
AB  - BACKGROUND: What determines inter-individual variability to impairments in
      behavioural control that may underlie road-traffic accidents, and impulsive and
      violent behaviours occurring under the influence of cannabis, the most widely
      used illicit drug worldwide? METHOD: Employing a double-blind, repeated-measures
      design, we investigated the genetic and neural basis of variable sensitivity to
      cannabis-induced behavioural dyscontrol in healthy occasional cannabis users.
      Acute oral challenge with placebo or Delta9-tetrahydrocannabinol (THC), the main
      psychoactive ingredient in cannabis, was combined with functional magnetic
      resonance imaging, while participants performed a response inhibition task that
      involved inhibiting a pre-potent motor response. They were genotyped for
      rs1130233 single nucleotide polymorphisms (SNPs) of the protein kinase B (AKT1)
      gene. RESULTS: Errors of inhibition were significantly (p = 0.008) increased
      following administration of THC in carriers of the A allele, but not in G allele
      homozygotes of the AKT1 rs1130233 SNP. The A allele carriers also displayed
      attenuation of left inferior frontal response with THC evident in the sample as a
      whole, while there was a modest enhancement of inferior frontal activation in the
      G homozygotes. There was a direct relationship (r = -0.327, p = 0.045) between
      the behavioural effect of THC and its physiological effect in the inferior
      frontal gyrus, where AKT1 genotype modulated the effect of THC. CONCLUSIONS:
      These results require independent replication and show that differing
      vulnerability to acute psychomotor impairments induced by cannabis depends on
      variation in a gene that influences dopamine function, and is mediated through
      modulation of the effect of cannabis on the inferior frontal cortex, that is rich
      in dopaminergic innervation and critical for psychomotor control.

PMID- 25065545
TI  - The quality of reporting of phase II and III trials for new antipsychotics: a
      systematic review.
AB  - BACKGROUND: The findings of the Clinical Antipsychotic Trials of Intervention
      Effectiveness (CATIE) study and the Cost Utility of the Latest Antipsychotic
      Drugs in Schizophrenia Study (CUtLASS) called previous trials of antipsychotics
      into question, including pre-licensing trials. Concerns regarding methodological
      robustness and quality of reporting increased. This systematic review aimed to
      examine the quality of reporting of phase II and III trials for new
      antipsychotics in the aftermath of the CATIE and CUtLASS studies. METHOD:
      Electronic searches were conducted in EMBASE, Medline and Cochrane databases and
      also ClinicalTrials.gov for antipsychotic trials (published between January 2006
      and February 2012). Phase II and III randomized controlled trials (RCTs) for
      iloperidone, asenapine, paliperidone, olanzapine, lurasidone and pomaglumetad
      methionil were selected for schizophrenia and schizoaffective disorder. The
      reporting of the methodology was evaluated in accordance with Consolidated
      Standards of Reporting Trials (CONSORT) guidelines. RESULTS: Thirty-one articles
      regarding 32 studies were included. There was insufficient reporting of design in
      47% of studies and only 13% explicitly stated a primary hypothesis. Exclusion
      criteria were poorly reported for diagnosis in 22% of studies. Detail regarding
      comparators, particularly placebos, was suboptimal for 56% of studies, and
      permitted concomitant medication was often not reported (19%). Randomization
      methods were poorly described in 56% of studies and reporting on blinding was
      insufficient in 84% of studies. Sample size calculations were insufficiently
      reported in 59% of studies. CONCLUSIONS: The quality of reporting of phase II and
      III trials for new antipsychotics does not reach the standards outlined in the
      CONSORT guidelines. Authors often fail to adequately report design and
      methodological processes, potentially impeding the progress of research on
      antipsychotic efficacy. Both policymakers and clinicians require high quality
      reporting before decisions are made regarding licensing and prescribing of new
      antipsychotics.

PMID- 25065546
TI  - Pathology of a lesion ablated from inside the coronary sinus.

PMID- 25065547
TI  - A spider's biological vibration filter: micromechanical characteristics of a
      biomaterial surface.
AB  - A strain-sensing lyriform organ (HS-10) found on all of the legs of a Central
      American wandering spider (Cupiennius salei) detects courtship, prey and predator
      vibrations transmitted by the plant on which it sits. It has been suggested that
      the viscoelastic properties of a cuticular pad directly adjacent to the sensory
      organ contribute to the organ's pronounced high-pass characteristics. Here, we
      investigate the micromechanical properties of the cuticular pad biomaterial in
      search of a deeper understanding of its impact on the function of the vibration
      sensor. These properties are considered to be an effective adaptation for the
      selective detection of signals for frequencies >40 Hz. Using surface force
      spectroscopy mapping we determine the elastic modulus of the pad surface over a
      temperature range of 15-40  degrees C at various loading frequencies. In the
      glassy state, the elastic modulus was ~100 MPa, while in the rubbery state the
      elastic modulus decreased to 20 MPa. These data are analyzed according to the
      principle of time-temperature superposition to construct a master curve that
      relates mechanical properties, temperature and stimulus frequencies. By
      estimating the loss and storage moduli vs. temperature and frequency it was
      possible to make a direct comparison with electrophysiology experiments, and it
      was found that the dissipation of energy occurs within a frequency window whose
      position is controlled by environmental temperatures.

PMID- 25065548
TI  - Characterization of porous, dexamethasone-releasing polyurethane coatings for
      glucose sensors.
AB  - Commercially available implantable needle-type glucose sensors for diabetes
      management are robust analytically but can be unreliable clinically primarily due
      to tissue-sensor interactions. Here, we present the physical, drug release and
      bioactivity characterization of tubular, porous dexamethasone (Dex)-releasing
      polyurethane coatings designed to attenuate local inflammation at the tissue
      sensor interface. Porous polyurethane coatings were produced by the salt
      leaching/gas-foaming method. Scanning electron microscopy and micro-computed
      tomography (micro-CT) showed controlled porosity and coating thickness. In vitro
      drug release from coatings monitored over 2 weeks presented an initial fast
      release followed by a slower release. Total release from coatings was highly
      dependent on initial drug loading amount. Functional in vitro testing of glucose
      sensors deployed with porous coatings against glucose standards demonstrated that
      highly porous coatings minimally affected signal strength and response rate.
      Bioactivity of the released drug was determined by monitoring Dex-mediated, dose
      dependent apoptosis of human peripheral blood derived monocytes in culture. Acute
      animal studies were used to determine the appropriate Dex payload for the
      implanted porous coatings. Pilot short-term animal studies showed that Dex
      released from porous coatings implanted in rat subcutis attenuated the initial
      inflammatory response to sensor implantation. These results suggest that
      deploying sensors with the porous, Dex-releasing coatings is a promising strategy
      to improve glucose sensor performance.

PMID- 25065550
TI  - Biogeographical and taxonomic biases in tropical forest fragmentation research.
AB  - Despite several decades of research on the effects of fragmentation and habitat
      change on biodiversity, there remain strong biases in the geographical regions
      and taxonomic species studied. The knowledge gaps resulting from these biases are
      of particular concern if the forests most threatened with modification are also
      those for which the effects of such change are most poorly understood. To
      quantify the nature and magnitude of such biases, we conducted a systematic
      review of the published literature on forest fragmentation in the tropics for the
      period 1980-2012. Studies included focused on any type of response of single
      species, communities, or assemblages of any taxonomic group to tropical forest
      fragmentation and on fragmentation-related changes to forests. Of the 853 studies
      we found in the SCOPUS database, 64% were conducted in the Neotropics, 13% in
      Asia, 10% in the Afrotropics, and 5% in Australasia. Thus, although the
      Afrotropics is subject to the highest rates of deforestation globally, it was the
      most disproportionately poorly studied biome. Significant taxonomic biases were
      identified. Of the taxonomic groups considered, herpetofauna was the least
      studied in the tropics, particularly in Africa. Research examining patterns of
      species distribution was by far the most common type (72%), and work focused on
      ecological processes (28%) was rare in all biomes, but particularly in the
      Afrotropics and for fauna. We suggest research efforts be directed toward less
      studied biogeographic regions, particularly where the threat of forest
      fragmentation continues to be high. Increased research investment in the
      Afrotropics will be important to build knowledge of threats and inform responses
      in a region where almost no efforts to restore its fragmented landscapes have yet
      begun and forest protection is arguably most tenuous.

PMID- 25065549
TI  - Enhanced depth-independent chondrocyte proliferation and phenotype maintenance in
      an ultrasound bioreactor and an assessment of ultrasound dampening in the
      scaffold.
AB  - Chondrocyte-seeded scaffolds were cultured in an ultrasound (US)-assisted
      bioreactor, which supplied the cells with acoustic energy around resonance
      frequencies (~5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and
      chitosan-n-butanol (CSB) based scaffolds with varying porosities were chosen and
      the following US regimen was employed: 15 kPa and 60 kPa, 5 min per application
      and 6 applications per day for 21 days. Non-stimulated scaffolds served as
      control. For BM scaffolds, US stimulation significantly impacted cell
      proliferation and depth-independent cell population density compared to controls.
      The highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US-treated BM
      scaffolds compared to controls. A similar trend was noted on US-treated cell
      seeded CS and CSB scaffolds, though COL2A1/COL1A1 ratios were significantly lower
      compared to BM scaffolds. Expression of Sox-9 was also elevated under US and
      paralleled the COL2A1/COL1A1 ratio. As an original contribution, a simplified
      mathematical model based on Biot theory was developed to understand the
      propagation of the incident US wave through the scaffolds and the model analysis
      was connected to cellular responses. Scaffold architecture influenced the
      distribution of US field, with the US field being the least attenuated in BM
      scaffolds, thus coupling more mechanical energy into cells, and leading to
      increased cellular activity.

PMID- 25065551
TI  - The Arabidopsis nitrate transporter NRT2.5 plays a role in nitrate acquisition
      and remobilization in nitrogen-starved plants.
AB  - Nitrogen is a key mineral nutrient playing a crucial role in plant growth and
      development. Understanding the mechanisms of nitrate uptake from the soil and
      distribution through the plant in response to nitrogen starvation is an important
      step on the way to improve nitrogen uptake and utilization efficiency for better
      growth and productivity of plants, and to prevent negative effects of nitrogen
      fertilizers on the environment and human health. In this study, we show that
      Arabidopsis NITRATE TRANSPORTER 2.5 (NRT2.5) is a plasma membrane-localized high
      affinity nitrate transporter playing an essential role in adult plants under
      severe nitrogen starvation. NRT2.5 expression is induced under nitrogen
      starvation and NRT2.5 becomes the most abundant transcript amongst the seven NRT2
      family members in shoots and roots of adult plants after long-term starvation.
      GUS reporter analyses showed that NRT2.5 is expressed in the epidermis and the
      cortex of roots at the root hair zone and in minor veins of mature leaves.
      Reduction of NRT2.5 expression resulted in a decrease in high-affinity nitrate
      uptake without impacting low-affinity uptake. In the background of the high
      affinity nitrate transporter mutant nrt2.4, an nrt2.5 mutation reduced nitrate
      levels in the phloem of N-starved plants further than in the single nrt2.4
      mutants. Growth analyses of multiple mutants between NRT2.1, NRT2.2, NRT2.4, and
      NRT2.5 revealed that NRT2.5 is required to support growth of nitrogen-starved
      adult plants by ensuring the efficient uptake of nitrate collectively with
      NRT2.1, NRT2.2 and NRT2.4 and by taking part in nitrate loading into the phloem
      during nitrate remobilization. 

PMID- 25065552
TI  - The effects of 3D bioactive glass scaffolds and BMP-2 on bone formation in rat
      femoral critical size defects and adjacent bones.
AB  - Reconstruction of critical size defects in the load-bearing area has long been a
      challenge in orthopaedics. In the past, we have demonstrated the feasibility of
      using a biodegradable load-sharing scaffold fabricated from poly(propylene
      fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2
      (BMP-2) to successfully induce healing in those defects. However, there is
      limited osteoconduction observed with the PPF/TCP scaffold itself. For this
      reason, 13-93 bioactive glass scaffolds with local BMP-2 delivery were
      investigated in this study for inducing segmental defect repairs in a load
      bearing region. Furthermore, a recent review on BMP-2 revealed greater risks in
      radiculitis, ectopic bone formation, osteolysis and poor global outcome in
      association with the use of BMP-2 for spinal fusion. We also evaluated the
      potential side effects of locally delivered BMP-2 on the structures of adjacent
      bones. Therefore, cylindrical 13-93 glass scaffolds were fabricated by indirect
      selective laser sintering with side holes on the cylinder filled with dicalcium
      phosphate dehydrate as a BMP-2 carrier. The scaffolds were implanted into
      critical size defects created in rat femurs with and without 10 MUg of BMP-2. The
      x-ray and micro-CT results showed that a bridging callus was found as soon as
      three weeks and progressed gradually in the BMP group while minimal bone
      formation was observed in the control group. Degradation of the scaffolds was
      noted in both groups. Stiffness, peak load and energy to break of the BMP group
      were all higher than the control group. There was no statistical difference in
      bone mineral density, bone area and bone mineral content in the tibiae and
      contralateral femurs of the control and BMP groups. In conclusion, a 13-93
      bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its
      potential application in treating large bone defects.

PMID- 25065553
TI  - The need to identify new P2Y12 receptor inhibitors in the management and
      prevention of arterial thrombosis.

PMID- 25065554
TI  - Increased serum concentrations of pentosidine are related to presence and
      severity of coronary artery disease.
AB  - BACKGROUND: There are limited data regarding the contribution of advanced
      glycation end products (AGEs) in the presence of coronary artery disease (CAD).
      We investigated whether serum pentosidine and Nepsilon-carboxymethyllysine (CML)
      were related to the presence and the severity of CAD. METHODS: 69 Tunisian
      patients with CAD (>= 50% obstruction in >= 1 coronary artery), 32 Tunisian
      patients without CAD but with potential cardiovascular risk factors and 60
      Tunisian control subjects were included in a cross-sectional study. Patients were
      classified as CAD and non CAD patients according to angiographic results. The
      severity of CAD was assessed using the Gensini score. Serum pentosidine and CML
      were measured by LC-MS/MS. RESULTS: Serum pentosidine and CML concentrations were
      significantly higher in non-CAD patients vs control subjects (P<0.001). Serum
      pentosidine concentrations were significantly higher in CAD patients vs non-CAD
      patients (P<0.001). A multiple logistic regression analysis demonstrated that
      pentosidine was independently associated with the presence of CAD (OR=1.52, 95%
      CI: 1.12-2.07, P=0.007). The area under curve (AUC) determined by ROC analysis
      was 0.74 (95% CI: 0.64-0.84, P<0.001) and the optimal cut-off value of
      pentosidine to predict the presence of CAD was 3.2 MUmol/mol Lys, with 64%
      sensitivity and 78% specificity. Furthermore, in a multivariate stepwise
      regression analysis, pentosidine was independently correlated with Gensini score
      (standardized beta= 0.46, 95% CI: 0.70-1.99, P<0.001). CONCLUSIONS: High
      concentrations of pentosidine show the presence and the severity of CAD with high
      sensitivity.

PMID- 25065555
TI  - The alpha-2-antiplasmin Arg407Lys polymorphism is associated with abdominal
      aortic aneurysm.
AB  - INTRODUCTION: Abdominal Aortic Aneurysm (AAA) involves dilatation of the
      abdominal aorta, with a natural history of expansion and eventual rupture. We
      have previously shown that AAA patients form denser clots with smaller pores,
      which are more resistant to fibrinolysis. The aim of this study was to use
      functional polymorphisms of the fibrinolytic system to identify how changes to
      proteins involved in fibrinolysis may play a role in the development of AAA.
      METHODS: Caucasian subjects >= 55 years (602 AAA patients and 490 matched
      controls) were genotyped for four polymorphisms (alpha-2-antiplasmin alpha2AP
      Arg6Trp and Arg407Lys, Thrombin-activatable fibrinolysis inhibitor TAFI Thr325Ile
      and tissue plasminogen activator tPA 7351C->T). DNA was extracted from blood, and
      genotype identified using real time PCR. Fibrin clot structure was analysed by
      permeation and turbidity in a subset of patients and controls. RESULTS: Genotypes
      across the study population were in Hardy-Weinberg Equilibrium. The two alpha2AP
      polymorphisms, Arg6Trp and Arg407Lys were in linkage disequilibrium (P<0.0001),
      and possession of a 407Lys allele negatively associated with AAA (odds ratio
      0.833, CI95 0.7-0.991, P=0.040). The TAFI Thr325Ile and the tPA 7351C->T
      polymorphisms were not associated with AAA. The alpha2AP 407Lys allele was not
      associated with in-vitro fibrinolysis times in plasma from patients with AAA.
      CONCLUSION: Possession of the alpha2AP 407Lys allele was negatively associated
      with AAA, and thus changes in alpha2AP may affect aneurysm growth and
      development. These data indicate that the regulation of plasmin activity (through
      binding to alpha2AP), rather than plasmin generation (TAFI, tPA), may play a role
      in AAA.

PMID- 25065556
TI  - Thrombomodulin-modified thrombin generation testing detects a hypercoagulable
      state in patients with cirrhosis regardless of the exact experimental conditions.

PMID- 25065557
TI  - Heparanase procoagulant activity is elevated and predicts survival in non-small
      cell lung cancer patients.
AB  - BACKGROUND: Heparanase is implicated in angiogenesis and tumor progression. We
      had earlier demonstrated that heparanase may also affect the hemostatic system in
      a non-enzymatic manner. It forms a complex and enhances the activity of the blood
      coagulation initiator- tissue factor (TF). Although increased heparanase antigen
      level in the plasma and biopsies of cancer patients was previously demonstrated,
      in the present study we evaluated, for the first time, the heparanase
      procoagulant activity in the plasma of patients with lung cancer. MATERIALS AND
      METHODS: Sixty five patients with non-small cell lung cancer at presentation and
      twenty controls were recruited. Plasma was studied for TF / heparanase
      procoagulant activity, TF activity and heparanase procoagulant activity using
      chromogenic assay and heparanase antigen levels by ELISA. RESULTS: Heparanase
      antigen levels were higher in the study group compared to control (P=0.05). TF /
      heparanase activity, and even more apparent, heparanase procoagulant activity
      were significantly higher in the study group compared to controls (P=0.008,
      P<0.0001, respectively). No significant difference was observed in the TF
      activity between the groups. Survival of patients with heparanase procoagulant
      activity higher than 31 ng/ml predicted a mean survival of 9 +/- 1.3 months while
      heparanase procoagulant activity of 31 ng/ml or lower predicted a mean survival
      of 24 +/- 4 months (P=0.001). Heparanase procoagulant activity was higher than 31
      ng/ml in the four cases of thrombosis detected during the follow-up period.
      CONCLUSIONS: Elevated heparanase procoagulant activity in patients with lung
      cancer reveals a new mechanism of coagulation system activation in malignancy.
      Heparanase procoagulant activity can potentially be used as a predictor for
      survival.

PMID- 25065558
TI  - oxLDL - the molecule linking hypercoagulability with the presence of
      cardiovascular disease in hemodialyzed uraemic patients.
AB  - INTRODUCTION: Patients with end-stage renal disease (ESRD) exhibit features of a
      hypercoagulable state, which may contribute to cardiovascular complications. Data
      from "in vitro" studies suggest that cell-free plasma lipids and lipoproteins may
      be capable to support thrombin generation. The aim of this study has been to
      establish the role of plasma oxidized LDL (oxLDL) in the coagulation activation
      in hemodialyzed (HD) patients with and without cardiovascular disease (CVD).
      MATERIALS AND METHODS: We examined relationship between a marker of coagulation
      activation - prothrombin fragments 1+2 (F1+2), and plasma oxLDL levels in 60 HD
      patients with and without CVD and in 20 healthy controls. RESULTS: F1+2 levels
      were significantly higher in HD patients than in controls, and they were higher
      in HD patients with CVD compared to those without CVD (p<0.001). Conversely,
      oxLDL levels were similar in HD patients with CVD and healthy controls, whereas
      this parameter was lower in HD patients without CVD when compared to controls and
      patients with CVD (both p<0.01). Close positive and independent association was
      between F1+2 and oxLDL levels in HD patients. Nitrates treatment and the presence
      of pyelonephritis were associated with reduced oxLDL as well as
      hypercoagulability in HD patients with cardiovascular complications. CONCLUSION:
      This study demonstrates the independent association between oxLDL and the marker
      of coagulation activation - F1+2 in HD patients. This new observation may offer a
      better understanding of the complex mechanism leading to hypercoagulability,
      which is markedly intensified in these patients, particularly in those with CVD.

PMID- 25065559
TI  - Assembly and multiple gene expression of thermophilic enzymes in Escherichia coli
      for in vitro metabolic engineering.
AB  - In vitro reconstitution of an artificial metabolic pathway is an emerging
      approach for the biocatalytic production of industrial chemicals. However,
      several enzymes have to be separately prepared (and purified) for the
      construction of an in vitro metabolic pathway, thereby limiting the practical
      applicability of this approach. In this study, genes encoding the nine
      thermophilic enzymes involved in a non-ATP-forming chimeric glycolytic pathway
      were assembled in an artificial operon and co-expressed in a single recombinant
      Escherichia coli strain. Gene expression levels of the thermophilic enzymes were
      controlled by their sequential order in the artificial operon. The specific
      activities of the recombinant enzymes in the cell-free extract of the multiple
      gene-expression E. coli were 5.0-1,370 times higher than those in an enzyme
      cocktail prepared from a mixture of single-gene-expression strains, in each of
      which a single one of the nine thermophilic enzymes was overproduced. Heat
      treatment of a crude extract of the multiple-gene-expression cells led to the
      denaturation of indigenous proteins and one-step preparation of an in vitro
      synthetic pathway comprising only a limited number of thermotolerant enzymes.
      Coupling this in vitro pathway with other thermophilic enzymes including the H2 O
      forming NADH oxidase or the malate/lactate dehydrogenase facilitated one-pot
      conversion of glucose to pyruvate or lactate, respectively.

PMID- 25065560
TI  - A horizon scan for species conservation by zoos and aquariums.
AB  - We conducted the first horizon scan for zoos and aquariums to identify the 10
      most important emerging issues for species conservation. This involved input from
      more than 100 experts from both the wider conservation community and the world
      zoo and aquarium community. Some of the issues are globally important: diseases,
      zoonoses, and biosecurity issues; new (communication) technologies; global water
      shortage and food insecurity; developing economies and markets for wildlife
      consumption; changes in wildlife population dynamics; and political instability
      and conflicts. Other issues are more specific to zoos and aquariums: need for
      extractive reserves; space shortage in zoos and aquariums; need for
      metapopulation management; and demand for caring of more species in zoos and
      aquariums. We also identified some broad approaches to these issues. Addressing
      the emerging issues identified in our horizon scan will further increase the
      contribution of the world zoo and aquarium community to global biodiversity
      conservation.

PMID- 25065561
TI  - Label-free profiling of skeletal muscle using high-definition mass spectrometry.
AB  - We report automated and time-efficient (2 h per sample) profiling of muscle using
      ultra-performance LC coupled directly with high-definition MS (HDMS(E)). Soluble
      proteins extracted from rat gastrocnemius (n = 10) were digested with trypsin and
      analyzed in duplicate using a 90 min RPLC gradient. Protein identification and
      label-free quantitation were performed from HDMS(E) spectra analyzed using
      Progenesis QI for Proteomics software. In total 1514 proteins were identified. Of
      these, 811 had at least three unique peptides and were subsequently used to
      assess the dynamic range and precision of LC-HDMS(E) label-free profiling.
      Proteins analyzed by LC-HDMS(E) encompass the entire complement of glycolytic,
      beta-oxidation, and tricarboxylic acid enzymes. In addition, numerous components
      of the electron transport chain and protein kinases involved in skeletal muscle
      regulation were detected. The dynamic range of protein abundances spanned four
      orders of magnitude. The correlation between technical replicates of the ten
      biological samples was R(2) = 0.9961 +/- 0.0036 (95% CI = 0.9940 - 0.9992) and
      the technical CV averaged 7.3 +/- 6.7% (95% CI = 6.87 - 7.79%). This represents
      the most sophisticated label-free profiling of skeletal muscle to date.

PMID- 25065562
TI  - A study on the inhibition of VEGF expression in salivary gland adenoid cystic
      carcinoma cells via iNOS gene RNAi in vitro.
AB  - In this study, we aimed to explore the effect of inducible nitric oxide synthase
      (iNOS) on vascular endothelial growth factor (VEGF) expression in salivary gland
      adenoid cystic carcinoma (SACC). Using RNAi, we transfected chemically
      synthesised iNOS siRNA into ACC-M cells (a highly metastatic adenoid cystic
      carcinoma cell line) and detected the change in the gene and protein expression
      levels of iNOS and VEGF by qRT-PCR and Western blotting. A transwell invasiveness
      assay was used to examine the changes in invasive ability of ACC-M cells. Cell
      growth was determined using a CCK-8 assay. Apoptosis and cell-cycle phases were
      detected by flow cytometry. We found that silencing iNOS down-regulated the
      expression of VEGF and then inhibited cell growth and invasiveness of SACC cells,
      while it increased apoptosis. Therefore, we concluded that iNOS can regulate VEGF
      expression and iNOS may be a therapeutic target.

PMID- 25065563
TI  - High pathologic complete response in Her2-positive, early-stage breast cancer to
      a novel nonanthracycline neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy is widely used to downstage breast cancers
      before surgery and is an accepted standard of care among patients with early
      stage breast cancer in whom adjuvant chemotherapy would be recommended.
      Pathologic complete response (pCR) rate is a robust predictor of outcome for
      certain breast cancer subtypes, including Her2-overexpressing breast cancer. The
      incorporation of Her2-targeted therapies has significantly increased the pCR rate
      in the neoadjuvant setting. Although regimens composed of trastuzumab, nab
      paclitaxel, and vinorelbine have demonstrated clinical efficacy in patients with
      metastatic breast cancer, few studies have examined this combination in early
      stage Her2+ breast cancer. We hypothesized that the combination of neoadjuvant
      nab-paclitaxel followed by vinorelbine could represent a nonanthracycline-based
      treatment option for early-stage Her2-overexpressing breast cancer. PATIENTS AND
      METHODS: Patients received 4 cycles of nab-paclitaxel 260 mg/m(2) intravenously
      (IV) every 14 days for 4 cycles followed by vinorelbine 25 mg/m(2) IV weekly for
      12 weeks with concurrent trastuzumab (4 mg/kg loading dose, and then 2 mg/kg/wk).
      The primary endpoint was the rate of pCR. Secondary endpoints included clinical
      response, toxicity, and survival rates. RESULTS: A total of 27 patients were
      accrued to the trial. The median tumor size was 4.0 cm, and more than 50% of
      patients had axillary lymph node involvement. The pCR rate was 48.1%. Among the
      40% of patients who had hormone receptor-positive disease, the pCR rate was
      18.2%, compared with 68.8% among patients with estrogen receptor/progesterone
      receptor-negative tumors. CONCLUSIONS: The combination of trastuzumab with nab
      paclitaxel followed by vinorelbine was well tolerated and had promising activity
      in the neoadjuvant setting.

PMID- 25065564
TI  - Analysis of MET genetic aberrations in patients with breast cancer at MD Anderson
      Phase I unit.
AB  - BACKGROUND: c-MET is a receptor tyrosine kinase whose phosphorylation activates
      important proliferation pathways. MET amplification and mutation have been
      described in various malignancies, including breast cancer (BC), and c-MET
      overexpression is associated with worse survival outcomes in patients with BC. We
      describe MET mutation and amplification rates in a BC cohort of patients referred
      to a Phase I Unit. METHODS: We reviewed the electronic medical records of all
      patients with advanced BC tested for MET amplification, mutation, or both who
      were referred to the Department of Investigational Cancer Therapeutics at MD
      Anderson. RESULTS: A total of 107 patients with advanced BC were analyzed for MET
      mutation/variant (88 patients) or amplification (63 patients). Of these, 49 were
      tested for both genetic abnormalities. Three of 63 patients (4.7%) demonstrated
      MET gene amplification by fluorescence in situ hybridization (2 in primary
      tissue; 1 in metastatic site). MET mutation/variant was detected in 8 of 88
      patients (9%). High-grade tumors were characteristic of all patients harboring
      MET amplification and were present in 7 of 8 (87.5%) of those with MET mutation.
      Metastatic sites were greater in MET-amplified compared with wild-type patients
      (median of 7 vs. 3 sites). Five of 8 patients (62.5%) with MET mutations had
      triple negative BC compared with 46% in controls. In addition, patients with
      positive test results for MET aberrations (n = 11) had inferior overall survival
      (OS) from Phase I consult compared with wild-type patients (n = 37), although
      this was not statistically significant (median OS = 9 vs. 15 months, P = .43).
      CONCLUSIONS: In this cohort of patients with BC who were referred to our Phase I
      Department, MET aberrations were associated with higher metastatic burden and
      high-grade histology. We could not demonstrate differences in survival outcomes
      because of a small sample size.

PMID- 25065565
TI  - The oncologic safety and practicality of breast conservation surgery in large
      breast tumors 5 centimeters or more.
AB  - BACKGROUND: Surgery remains a therapeutic strategy for women with breast cancer,
      and long-term outcomes for breast conservation surgery (BCS) and radiotherapy are
      equivalent to those for mastectomy. To date, there are few published data
      assessing the oncologic safety and practicality of BCS in women with large breast
      cancers >= 5 cm. The current study compares survival outcomes for women with
      breast cancer >= 5 cm undergoing BCS or mastectomy. METHODS: All women undergoing
      surgery for breast cancer >= 5 cm between January 2004 and December 2011 were
      included in this study. Kaplan-Meier survival curves statistically compared the
      overall survival (OS), disease-free survival (DFS), and local recurrence-free
      survival (LRFS) in the BCS and mastectomy groups. Statistical analysis involved
      chi-square analysis and t test. The mean length of follow-up was 55.25 months
      (range, 6-115 months). RESULTS: A total of 217 women had surgery for tumors >= 5
      cm (BCS in 51, mastectomy in 166). There was no statistical difference in the OS,
      DFS, and LRFS between groups (P = .439; 95% confidence interval, 0.114-0.347).
      The re-excision rate of women undergoing BCS was 45.1%, with 65.2% of women
      undergoing a completion mastectomy. Extensive ductal carcinoma in situ
      represented the only significant risk factor associated with inadequate margins
      (P = .021). Larger tumor size was associated with a greater risk of local
      recurrence (P = .039). CONCLUSIONS: This study is one of the largest studies to
      date to report BCS + radiotherapy as a safe oncologic treatment option for women
      with large breast cancers. However, the higher re-excision rate advocates a need
      to investigate ways to improve patient selection.

PMID- 25065566
TI  - Adverse event management of mTOR inhibitors during treatment of hormone receptor
      positive advanced breast cancer: considerations for oncologists.
AB  - Breast cancer (BC) is diagnosed in nearly 1 in 3 women with cancer in the United
      States; one third of these patients have regional lymph node metastases at the
      time of diagnosis. The 5-year survival rate of patients with metastatic BC is
      very low, and approximately 40,000 women were expected to die of the disease in
      2013. About 75% of patients with BC have hormone receptor-positive (HR(+))
      disease, which is often managed with endocrine therapy; however, most patients
      eventually have resistance to these therapies. Recently, the mammalian target of
      rapamycin (mTOR) inhibitor everolimus, in combination with exemestane, improved
      progression-free survival (PFS) of patients with advanced BC, leading to its
      approval by the US Food and Drug Administration. Because adverse events (AEs)
      associated with everolimus might differ from AEs that oncologists who treat
      patients with BC are more familiar with, everolimus AEs and their effective
      management are reviewed in this article. Possible dose adjustments of everolimus
      for patients with renal or hepatic impairment and strategies for minimizing
      potential interactions of everolimus with other drugs and food are also
      discussed. 

PMID- 25065567
TI  - Perioperative therapy for esophageal cancer.
AB  - Traditionally, surgery is considered the best treatment for esophageal cancer in
      terms of locoregional control and long-term survival, but survival after surgery
      alone for locally advanced esophageal cancer is not satisfactory. A
      multidisciplinary approach that includes surgery, radiotherapy, and chemotherapy,
      alone or in combination, has been developed to improve the prognosis. Multiple
      clinical trials have addressed the preferred treatment strategy, such as
      neoadjuvant or adjuvant and chemotherapy, radiotherapy, or chemoradiotherapy, in
      managing locally advanced esophageal cancer. In this review, we provide an update
      on treatment strategies for locally advanced esophageal cancers. Recent studies
      indicate that neoadjuvant chemoradiotherapy or chemotherapy has a survival
      benefit over surgery alone in this patient group. Neoadjuvant chemoradiotherapy
      is an accepted standard of care in the United States while neoadjuvant
      chemotherapy is regarded as standard treatment in Japan and the United Kingdom.
      The standard treatment differs among countries because two large randomized
      controlled trials that evaluated the effectiveness of neoadjuvant chemotherapy
      reported conflicting results and no trial has made a comparison between
      neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy directly. Future
      trials in locally advanced esophageal cancer should focus on identifying the
      optimum strategy and its regimen and aim to minimize treatment toxicities and
      effects on quality of life. 

PMID- 25065568
TI  - Defective basement membrane in atopic dermatitis and possible role of IL-13.

PMID- 25065569
TI  - Hot avulsion: a modification of an existing technique for management of
      nonlifting areas of a polyp (with video).
AB  - BACKGROUND: Endoscopic management of the nonlifting areas of a colonic polyp is a
      significant challenge. The traditional approach has been to use ablative
      techniques with mixed long-term results. OBJECTIVE: To evaluate the safety and
      efficacy of hot avulsion (HA), a modification in the use of hot biopsy forceps in
      the management of the nonlifting areas of a colonic polyp. DESIGN: Retrospective
      review of data from a prospectively maintained colonic Endoscopic Mucosal
      Resection database. SETTING: Tertiary referral hospital. PATIENTS AND
      INTERVENTION: Twenty patients in whom HA was used as part of the polypectomy
      technique. MAIN OUTCOME MEASUREMENTS: Location and size of polyp, reasons for
      nonlifting, immediate success, residual rates, and adverse events. RESULTS: In
      our 20 patients studied, the main reasons for nonlifting were scarring from
      previous EMR attempts in 55% and scarring from previous biopsy in 35%. Mean size
      of avulsion was 4.4 mm (range, 1-15 mm). At the index procedure, HA was
      successful in removing macroscopic adenomatous tissue in all patients. At follow
      up examinations, 85% (17/20) had no macroscopic or microscopic neoplasia residual
      and 15% (3/20) had a small area of residual that was easily treated with repeat
      HA. There were no immediate or long-term adverse events. LIMITATIONS:
      Nonrandomized, single-center experience. CONCLUSIONS: HA appears to be a safe and
      effective adjunct treatment to snare polypectomy for nonlifting areas of a
      colonic polyp. Further randomized multicenter studies are required with direct
      comparison to established techniques.

PMID- 25065570
TI  - Clinical presentation and referral characteristics of food protein-induced
      enterocolitis syndrome in the United Kingdom.
AB  - BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a pediatric
      non-IgE-mediated allergic reaction to foods. The diagnosis of FPIES is clinical,
      with children presenting typically 2 to 4 hours after ingestion of a food
      protein. The most striking symptoms are vomiting, lethargy, and pallor.
      Misdiagnosis and delay in presentation to an allergist or gastroenterologist are
      common. OBJECTIVES: To investigate the pathway of patients with FPIES presenting
      to a specialist clinic in the United Kingdom to ascertain whether they
      experienced delays or misdiagnoses and to investigate their symptoms and
      triggers. METHODS: All patients with FPIES presenting over a 3-year period (2010
      2013) in a tertiary pediatric allergy clinic in London were analyzed
      retrospectively. This was performed by searching electronically for all patients
      with a diagnosis of FPIES and manually reviewing paper notes. Presenting symptoms
      and management pathways were collated. RESULTS: Fifty-four patients were
      identified, with an average age of onset at 8 months. They initially presented to
      medical professionals other than an allergist or gastroenterologist. The most
      frequent presenting symptom was vomiting followed by signs suggesting shock or
      hypotension and diarrhea. Differential diagnoses included gastroenteritis,
      sepsis, and surgical abnormalities. The main eliciting foods were cow's milk,
      fish, egg, soy, and wheat. CONCLUSION: In the United Kingdom, FPIES typically has
      its onset at 8 months. Patients experience a delay of 12 months in the diagnosis
      of FPIES and frequently have multiple episodes and interim diagnoses. A great
      need remains for enhanced education of medical practitioners dealing with
      children about the varied presentations of FPIES.

PMID- 25065571
TI  - Safety and clinical predictors of reacting to extensively heated cow's milk
      challenge in cow's milk-allergic children.
AB  - BACKGROUND: Many children with IgE-mediated allergy to cow's milk (CM) can
      tolerate CM in baked foods. OBJECTIVE: To define the clinical characteristics and
      severity of reactions to baked CM in children with CM allergy (CMA) at an oral
      food challenge (OFC). METHODS: Children with CMA presenting to a tertiary clinic
      from 2010 through 2013 with complete dietary CM avoidance were offered a baked CM
      OFC. Challenges were performed with incremental dosages to a total of 1 baked
      muffin. RESULTS: Seventy children with CMA underwent a baked CM OFC. Fifty-one
      children (73%) passed the OFC and successfully incorporated baked CM into their
      diet. Nineteen children (27%) reacted to their challenge. Of reactors, 4 (21%)
      developed anaphylaxis and required intramuscular adrenalin. Predictors of
      clinical reactivity to baked CM were asthma, asthma requiring preventer therapy,
      IgE-mediated clinical reactions to more than 3 food groups, and those with a
      history of CM anaphylaxis. CONCLUSION: This study identified factors that were
      predictors of clinical reactivity to baked CM in this cohort of children with
      CMA. These risk factors do not represent contradictions to a baked CM challenge
      but may allow for risk stratification of challenges. Given the potential for
      anaphylaxis, an OFC to baked CM should be done under medical supervision in those
      children with CMA who have been strictly avoiding all CM.

PMID- 25065572
TI  - Successful desensitization with anakinra in a case with immediate
      hypersensitivity reaction.

PMID- 25065573
TI  - Is there a better way?

PMID- 25065575
TI  - Schizophrenia and violent crime: a population-based study.
AB  - BACKGROUND: Previous studies have found that patients with schizophrenia are more
      likely to be violent than the general population. The aim of this study was to
      investigate the association between schizophrenia and violent crime in the
      Israeli population. METHOD: Using the Israeli Psychiatric Hospitalization Case
      Registry we identified 3187 patients with a discharge diagnosis of schizophrenia.
      For each proband we identified parents and siblings, and gender- and age-matched
      controls for patients, parents and siblings. Information on violent crimes was
      obtained from police records. RESULTS: Patients with schizophrenia were at
      increased risk for violent crimes compared with controls [odds ratio (OR) 4.3,
      95% confidence interval (CI) 3.8-4.9], especially women (OR 9.9, 95% CI 6.2
      15.7). Risk for violent crimes was higher among patients with co-morbid substance
      misuse than in patients without such co-morbidity (OR 5.1, 95% CI 4.2-6.3).
      CONCLUSIONS: The results of this study suggest that increased risk of violence is
      part of the clinical picture of schizophrenia and needs to be recognized as a
      legitimate, essential, aspect of clinical management.

PMID- 25065576
TI  - Development of a liquid chromatography-mass spectrometry method for determination
      of agrimol B in rat plasma: application to preclinical pharmacokinetics.
AB  - A sensitive and accurate liquid chromatography coupled with mass spectrometry (LC
      MS) method was developed for the determination of agrimol B, a main active
      ingredient isolated from Agrimonia pilosa Ledeb., in rat plasma. Chromatographic
      separation was achieved on a Zorbax CN column (150 * 4.6 mm, 5 um), with
      isocratic elution consisting of acetonitrile and water (15:85, v/v) at a flow
      rate of 0.6 mL/min. Agrimol B and dryocrassin ABBA, an internal standard (IS),
      were analyzed by selected ion monitoring at m/z transitions of 681.3 and 819.4,
      respectively. This assay exhibited a good linearity with a correlation
      coefficient >0.99 and showed no endogenous interference with the analyte and IS.
      The limit of quantification of agrimol B was 8.025 ng/mL with acceptable
      precision and accuracy. The method was successfully applied in the
      pharmacokinetic study of agrimol B in rats after intravenous (1 mg/kg) and oral
      (2, 5 and 10 mg/kg) doses of agrimol B. The absolute bioavailability of agrimol B
      was 16.4-18.0% in rat. Our study clarifies the pharmacokinetic behavior of
      agrimol B in animals.

PMID- 25065577
TI  - Phospholipase D facilitates efficient entry of influenza virus, allowing escape
      from innate immune inhibition.
AB  - Lipid metabolism plays a fundamental role during influenza virus replication,
      although key regulators of lipid-dependent trafficking and virus production
      remain inadequately defined. This report demonstrates that infection by influenza
      virus stimulates phospholipase D (PLD) activity and that PLD co-localizes with
      influenza during infection. Both chemical inhibition and RNA interference of PLD
      delayed viral entry and reduced viral titers in vitro. Although there may be
      contributions by both major isoenzymes, the effects on viral infectivity appear
      to be more dependent on the PLD2 isoenzyme. In vivo, PLD2 inhibition reduced
      virus titer and correlated with significant increases in transcription of innate
      antiviral effectors. The reduction in viral titer downstream of PLD2 inhibition
      was dependent on Rig-I (retinoic acid-inducible gene-1), IRF3, and MxA (myxovirus
      resistance gene A) but not IRF7. Inhibition of PLD2 accelerated the accumulation
      of MxA in foci as early as 30 min postinfection. Together these data suggest that
      PLD facilitates the rapid endocytosis of influenza virus, permitting viral escape
      from innate immune detection and effectors that are capable of limiting lethal
      infection. 

PMID- 25065578
TI  - The effect of age on DNA concentration from whole saliva: implications for the
      standard isolation method.
AB  - OBJECTIVES: Adequate quantity and quality of the DNA isolated from saliva samples
      are crucial for ensuring successful genotyping rates in genetic studies. However,
      there is little information about these issues when saliva samples are collected
      from children. The objectives of this study were to assess whether there are
      differences in DNA quality or quantity isolated from saliva samples of children
      at different ages and adolescents compared to adults and, if so, to establish a
      modified protocol to improve and standardize DNA isolation from saliva samples of
      children. METHODS: Saliva samples were collected with Oragene DNA Sample
      Collection Kit from 41 healthy subjects including children of different ages,
      adolescents, and adults. Quantity and quality of isolated DNA were determined
      spectrophotometrically. RESULTS: DNA concentration and age were positively
      correlated (r = 0.676, P < 0.001). A high percentage of samples from children
      below 12 years yielded DNA concentrations <100 ng/uL and DNA quality a260/a280
      ratios of <1.8. Modifying the standard DNA isolation method raised DNA quantity
      and quality in these critical samples. CONCLUSIONS: Age determines, at least in
      part, the high variability observed in the concentration of DNA isolated from
      saliva samples. This fact should be taken into account for a better
      standardization of the DNA isolation to ensure DNA banking in large-scale genetic
      studies involving children.

PMID- 25065579
TI  - Reactivity and mass transfer of low-dimensional catalysts.
AB  - Understanding the mechanisms governing chemical and morphological changes induced
      by an ambient-pressure gas and how such changes influence the activity of
      heterogeneous catalysts is central to the formation of a predictive capability
      for structure-reactivity relationships. With techniques such as ambient-pressure
      photoelectron spectroscopy, scanning tunneling microscopy, and surface X-ray
      diffraction, active phases and reaction intermediates can be probed in situ on
      relevant samples to form a comprehensive picture of this dynamic interplay
      between gases and surfaces. Of particular interest is the interaction of oxygen
      and carbon monoxide with catalysts. We will describe how model systems of
      increased complexity can be used to investigate gas-mediated mass transfer
      processes that may occur even at relatively modest temperatures. Furthermore, we
      will discuss how the morphology may be tailored to study specific contributions
      from defect sites and charge transfer to catalytic activity. 

PMID- 25065574
TI  - Childhood intermittent and persistent rhinitis prevalence and climate and
      vegetation: a global ecologic analysis.
AB  - BACKGROUND: The effect of climate change and its effects on vegetation growth,
      and consequently on rhinitis, are uncertain. OBJECTIVE: To examine between- and
      within-country associations of climate measures and the normalized difference
      vegetation index with intermittent and persistent rhinitis symptoms in a global
      context. METHODS: Questionnaire data from 6- to 7-year-olds and 13- to 14-year
      olds were collected in phase 3 of the International Study of Asthma and Allergies
      in Childhood. Associations of intermittent (>1 symptom report but not for 2
      consecutive months) and persistent (symptoms for >=2 consecutive months) rhinitis
      symptom prevalences with temperature, precipitation, vapor pressure, and the
      normalized difference vegetation index were assessed in linear mixed-effects
      regression models adjusted for gross national income and population density. The
      mean difference in prevalence per 100 children (with 95% confidence intervals
      [CIs]) per interquartile range increase of exposure is reported. RESULTS: The
      country-level intermittent symptom prevalence was associated with several country
      level climatic measures, including the country-level mean monthly temperature
      (6.09  degrees C; 95% CI, 2.06-10.11 degrees C per 10.4  degrees C),
      precipitation (3.10 mm; 95% CI, 0.46-5.73 mm; per 67.0 mm), and vapor pressure
      (6.21 hPa; 95% CI, 2.17-10.24 hPa; per 10.4 hPa) among 13- to 14-year-olds (222
      center in 94 countries). The center-level persistent symptom prevalence was
      positively associated with several center-level climatic measures. Associations
      with climate were also found for the 6- to 7-year-olds (132 center in 57
      countries). CONCLUSION: Several between- and within-country spatial associations
      between climatic factors and intermittent and persistent rhinitis symptom
      prevalences were observed. These results provide suggestive evidence that climate
      (and future changes in climate) may influence rhinitis symptom prevalence.

PMID- 25065580
TI  - Increased minimum vein diameter on preoperative mapping with duplex ultrasound is
      associated with arteriovenous fistula maturation and secondary patency.
AB  - OBJECTIVE: Autogenous arteriovenous hemodialysis accesses (arteriovenous fistulas
      [AVFs]) are preferred for chronic hemodialysis access. Preoperative vein mapping
      by duplex ultrasound is recommended before AVF creation, but there are few data
      correlating vein diameter with postoperative outcomes. Also, vein diameter has
      not been included in prior predictive models of fistula maturation. This study
      aims to test whether preoperative vein diameter is associated with failure of AVF
      maturation and long-term (secondary) patency. METHODS: We performed a
      retrospective analysis of clinical variables of patients undergoing
      brachiobasilic or brachiocephalic AVF creation. Kaplan-Meier and multivariate Cox
      regression models tested whether preoperative minimum vein diameter (MVD) and
      clinical covariates were associated with failure of AVF maturation and secondary
      patency. RESULTS: The sample included 158 adults (54 +/- 14 years; 45% male; 61%
      white; 56% diabetes; body mass index, 32 +/- 8; MVD, 3.4 +/- 1.1 mm; follow-up,
      12 +/- 9 months [range, <1-40 months]). Increased MVD was associated with
      decreased risk of AVF failure. More than one third of AVFs with MVD <2.7 mm
      failed to mature within 6 months. Multivariate models that adjusted for age,
      diabetes, race, gender, body mass index, and preoperative dialysis status
      demonstrated that increased MVD was associated with decreased risk of failure of
      maturation and better long-term patency overall (P = .005 and P = .001,
      respectively). CONCLUSIONS: Patients with a larger MVD on preoperative vein
      mapping are at lower risk for failure of fistula maturation and have increased
      long-term AVF patency. MVD is the only clinical or demographic factor associated
      with both AVF maturation and long-term patency. MVD is an important preoperative
      indicator of fistula success in assessment of potential AVF sites. Future
      predictive models of fistula maturation and patency should include MVD.

PMID- 25065581
TI  - Predictors of 30-day postoperative stroke or death after carotid endarterectomy
      using the 2012 carotid endarterectomy-targeted American College of Surgeons
      National Surgical Quality Improvement Program database.
AB  - OBJECTIVE: This study used a recently released procedure-targeted multicenter
      data source to determine independent predictors of postoperative stroke or death
      in patients undergoing carotid endarterectomy (CEA) for carotid artery stenosis.
      METHODS: The 2012 CEA-targeted American College of Surgeons (ACS) National
      Surgical Quality Improvement Program (NSQIP) database was used for this study.
      Patient, disease, and procedure characteristics of patients undergoing CEA were
      assessed. Multivariate logistic regression analysis was used to determine
      independent risk factors for 30-day postoperative stroke/death or other major
      complications. RESULTS: The analysis included 3845 patients undergoing CEA (58.1%
      with asymptomatic and 41.9% with symptomatic carotid disease). The overall 30-day
      postoperative stroke/death rate was 3.0% (1.9% in asymptomatic patients, 4.6% in
      symptomatic patients). The variables that maintained an independent association
      with postoperative stroke/death after adjustment for other known patient-related
      and procedure-related factors were age >=80 years, active smoking, contralateral
      internal carotid artery stenosis of 80% to 99%, emergency procedure status,
      preoperative stroke, presence of one or more ACS NSQIP-defined high-risk
      characteristics (including any or all of New York Heart Association class III/IV
      congestive heart failure, left ventricular ejection fraction <30%, recent
      unstable angina, or recent myocardial infarction), and operative time >=150
      minutes. CONCLUSIONS: After adjustment for a comprehensive array of patient
      related and procedure-related variables of particular import to patients with
      carotid artery stenosis, we have identified several factors that are
      independently associated with early stroke or death after CEA. These factors are
      generally related to the comorbid condition of CEA patients and to specific
      characteristics of their carotid disease, and not to technical features of the
      CEA procedure. Knowledge of these factors will assist surgeons in selecting
      appropriate patients for this procedure.

PMID- 25065582
TI  - Quantification of residual limb skeletal muscle perfusion with contrast-enhanced
      ultrasound during application of a focal junctional tourniquet.
AB  - OBJECTIVE: Focal junctional tourniquets (JTs) have been developed to control
      hemorrhage from proximal limb injuries. These devices may permit greater
      collateral perfusion than circumferential tourniquets. We hypothesized that JTs
      eliminate large-vessel pulse pressure yet allow a small amount of residual limb
      perfusion that could be useful for maintaining tissue viability. METHODS: Ten
      healthy control subjects were studied. Transthoracic echocardiography, Doppler
      ultrasound of the femoral artery (FA) and posterior tibial artery, and contrast
      enhanced ultrasound (CEU) perfusion imaging of the anterior thigh extensor and
      calf plantar flexor muscles were performed at baseline and during application of
      a JT over the common FA. Intramuscular arterial pulsatility index was also
      measured from CEU intensity variation during the cardiac cycle. RESULTS: FA flow
      was eliminated by JTs in all subjects; posterior tibial flow was eliminated in
      all but one. Perfusion measured in the thigh and calf muscles was similar at
      baseline (0.33 +/- 0.29 vs 0.29 +/- 0.22 mL/min/g). Application of the JT
      resulted in a reduction of perfusion (P < .05) that was similar for the thigh and
      calf (0.08 +/- 0.07 and 0.10 +/- 0.03 mL/min/g). On CEU, microvascular flux rate
      was reduced by ~55%, and functional microvascular blood volume was reduced by
      ~35%. Arterial pulsatility index was reduced by ~90% in the calf. JT inflation
      did not alter left ventricle dimensions, fractional shortening, cardiac output,
      or arterial elastance as a measure of total systolic load. CONCLUSIONS:
      Application of a JT eliminates conduit arterial pulse and markedly reduces
      intramuscular pulse pressure, but thigh and calf skeletal muscle perfusion is
      maintained at 25% to 35% of basal levels. These data suggest that JTs that are
      used to control limb hemorrhage allow residual tissue perfusion even when pulse
      pressure is absent.

PMID- 25065583
TI  - The Agency for Healthcare Research and Quality Inpatient Quality Indicator #11
      overall mortality rate does not accurately assess mortality risk after abdominal
      aortic aneurysm repair.
AB  - OBJECTIVE: The Agency for Healthcare Research and Quality (AHRQ) Inpatient
      Quality Indicator (IQI) #11, abdominal aortic aneurysm (AAA) repair mortality
      rate, is a measure of hospital quality that is publically reported but has not
      been externally validated. Because the IQI #11 overall mortality rate includes
      both intact and ruptured aneurysms and open and endovascular repair, we
      hypothesized that IQI #11 overall mortality rate does not provide accurate
      assessment of mortality risk after AAA repair and that AAA mortality cannot be
      accurately assessed by a single quality measure. METHODS: Using AHRQ IQI software
      version 4.2, we calculated observed (O) and expected (E) mortality rates for IQI
      #11 for all hospitals performing more than 10 AAA repairs per year in the
      Nationwide Inpatient Sample for the years 2007 to 2011. We used Spearman
      correlation coefficient to compare expected rates as determined by IQI #11
      overall mortality rate risk adjustment methodology and observed rates for all AAA
      repairs in four cohorts stratified by aneurysm stability (ruptured vs intact) and
      method of repair (open vs endovascular). RESULTS: Among 187,773 AAA repairs
      performed at 1268 U.S. hospitals, hospitals' IQI #11 overall expected rates
      correlated poorly with their observed rates (E: 5.0% +/- 4.4% vs O: 6.0% +/-
      9.8%; r = .49). For ruptured AAAs, IQI #11 overall mortality rate methodology
      underestimated the mortality risk of open repair (E: 34% +/- 7.2% vs O: 40.1% +/-
      38.2%; r = 0.20) and endovascular repair (E: 24.8% +/- 9% vs O: 27.3% +/- 37.9%;
      r = 0.08). For intact AAA repair, IQI #11 overall mortality rate methodology
      underestimated the mortality risk of open repair (E: 4.3% +/- 2.4% vs O: 6.3% +/-
      16.1%; r = .24) but overestimated the mortality risk of endovascular repair (E:
      1.3% +/- 0.8% vs O: 1.1% +/- 3.7%; r = 0.25). Hospitals' observed mortality rates
      after intact AAA repair were not correlated with their mortality rates after
      ruptured AAA repair (r = 0.03). CONCLUSIONS: IQI #11 overall mortality rate fails
      to provide accurate assessment of inpatient mortality risk after AAA repair.
      Thus, it is inappropriate to use IQI #11 overall mortality rate for quality
      reporting. The accuracy of separate quality measures that assess mortality risk
      after repair of ruptured and intact AAAs, stratified by the use of open or
      endovascular repair, should be examined.

PMID- 25065584
TI  - Two patients with co-morbid myasthenia gravis in a Brazilian cohort of
      inflammatory bowel disease.
AB  - Co-morbid auto-immune disorders may affect 0.2% of the population. We present the
      clinical and electrodiagnostic findings of 2 patients with inflammatory bowel
      disease and myasthenia gravis from a Brazilian cohort of 218 inflammatory bowel
      disease patients. Patient 1: A 40year-old man was diagnosed with ulcerative
      colitis at age 37 and underwent total colectomy 3years later. After prednisone
      was tapered, he experienced a clinical relapse and was diagnosed with Crohn's
      disease. He then developed quadriparesis, bilateral ptosis, dysphagia and
      dysarthria. Patient 2: A 41year-old woman (diagnosed with ulcerative colitis and
      primary sclerosing cholangitis at age 35) developed speech impairment and ptosis.
      On both patients, symptoms quickly progressed over few weeks. Myasthenia gravis
      was diagnosed and confirmed by abnormal repetitive nerve stimulation and elevated
      anti-acetylcholine receptor antibody titers. Pyridostigmine and prednisone
      successfully treated both patients. Myasthenia gravis prevalence over 9years was
      0.9%. Myasthenia gravis clinical course was not significantly modified by
      inflammatory bowel disease relapses and should be suspected with new onset
      weakness. 

PMID- 25065586
TI  - The role of androst-5-ene-3beta,17beta-diol (androstenediol) in cell
      proliferation in endometrium of women with polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) show high prevalence of endometrial
      hyperplasia and adenocarcinoma. Endometrial proliferation is increased, evaluated
      by high levels of Ki67 (cell cycle marker) and low levels of p27 (negative
      regulator of cell cycle). Nevertheless, endometrial changes in cyclin D1
      (positive regulator of cell cycle) in PCOS-women are not described. Androst-5-ene
      3beta,17beta-diol (androstenediol), steroid with estrogenic activity present in
      endometria, could be related to increased endometrial cell proliferation. The
      objective of this study was to determine protein content of cyclin D1 and
      androstenediol levels in endometria from PCOS and control-women and to evaluate
      the possible mechanism favoring cell proliferation associated with hormonal
      characteristics of patients. Therefore, cyclin D1 protein content in PCOS-women
      and control-endometrial tissue were assessed by western blot and
      immunohistochemistry. The androstenediol levels were evaluated by ELISA. To
      further analyze the effect of steroids (androstenediol, 17beta-estradiol,
      testosterone) in cell proliferation, levels of proteins cyclin D1, p27 and Ki67
      were evaluated in an in vitro model of stromal endometrial cells T-HESC and St
      T1b. An increase in cyclin D1 and androstenediol was observed in tissues from
      PCOS-women relative to control group (p<0.05). In the in vitro model,
      androstenediol exerted increase in cyclin D1 (p<0.05) and a decrease in p27
      protein level (p<0.05), while Ki67 in St-T1b cells increased under this stimulus
      (p<0.05). Testosterone produces opposite effects in the levels of the above
      markers (p<0.05). Therefore, the hormonal imbalance associated with this syndrome
      could alter endometrial tissue homeostasis, promoting cell proliferation.
      Androstenediol is a molecule that could be involved by stimulating proliferation,
      whereas testosterone elicits a role of cell cycle repressor.

PMID- 25065587
TI  - Targeting thapsigargin towards tumors.
AB  - The skin irritating principle from Thapsia garganica was isolated, named
      thapsigargin and the structure elucidated. By inhibiting the sarco/endoplasmic
      reticulum Ca(2+) ATPase (SERCA) thapsigargin provokes apoptosis in almost all
      cells. By conjugating thapsigargin to peptides, which are only substrates for
      either prostate specific antigen (PSA) or prostate specific membrane antigen
      (PSMA) prodrugs were created, which selectively affect prostate cancer cells or
      neovascular tissue in tumors. One of the prodrug is currently tested in clinical
      phase II. The prodrug under clinical trial has been named mipsagargin. 

PMID- 25065585
TI  - The role of microRNAs and long non-coding RNAs in the pathology, diagnosis, and
      management of melanoma.
AB  - Melanoma is frequently lethal and its global incidence is steadily increasing.
      Despite the rapid development of different modes of targeted treatment, durable
      clinical responses remain elusive. A complete understanding of the molecular
      mechanisms that drive melanomagenesis is required, both genetic and epigenetic,
      in order to improve prevention, diagnosis, and treatment. There is increased
      appreciation of the role of microRNAs (miRNAs) in melanoma biology, including in
      proliferation, cell cycle, migration, invasion, and immune evasion. Data are also
      emerging on the role of long non-coding RNAs (lncRNAs), such as SPRY4-IT1, BANCR,
      and HOTAIR, in melanomagenesis. Here we review the data on the miRNAs and lncRNAs
      implicated in melanoma biology. An overview of these studies will be useful for
      providing insights into mechanisms of melanoma development and the miRNAs and
      lncRNAs that might be useful biomarkers or future therapeutic targets.

PMID- 25065588
TI  - A possible mechanism in DHEA-mediated protection against osteoarthritis.
AB  - Dehydroepiandrosterone (DHEA) and its ester form, DHEA-S, are the most abundant
      steroids in human plasma. Our previous studies showed that DHEA protects against
      osteoarthritis (OA). The aim of this paper was to explore the possible mechanisms
      that underlie DHEA-mediated protection against OA. We tested the expression of
      beta-catenin, it was increased significantly in OA. Rabbit cartilage was treated
      with various concentrations of DHEA in both IL-1beta-induced rabbit chondrocytes
      and in rabbit cartilage from the anterior cruciate ligament transaction-induced
      OA model. We found DHEA decreased the expression of beta-catenin. Then we further
      activated Wnt/beta-catenin signaling by beta-catenin transfection and inactivated
      it by the inhibitor Dickkopf1 in chondrocytes to reveal its role in the
      pathogenesis of OA. It turns out the protective effect of DHEA was significantly
      decreased when Wnt/beta-catenin signaling was activated, while inactivating
      Wnt/beta-catenin signaling enhanced the effects of DHEA. Therefore, we
      hypothesize that DHEA probably exerted its chondroprotective effect by regulating
      Wnt/beta-catenin signaling. Our findings demonstrate the critical role of
      Wnt/beta-catenin signaling in DHEA-mediated protection against OA.

PMID- 25065590
TI  - TRIM24 links glucose metabolism with transformation of human mammary epithelial
      cells.
AB  - Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone
      reader, recently associated with poor overall survival of breast-cancer patients.
      At a molecular level, TRIM24 is a negative regulator of p53 levels and a co
      activator of estrogen receptor. However, the role of TRIM24 in breast
      tumorigenesis remains largely unknown. We used an isogenic human mammary
      epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue,
      and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24 iHMECs)
      greatly increased cellular proliferation and induced malignant transformation.
      Subcutaneous injection of TRIM24 iHMECs in nude mice led to growth of
      intermediate to high-grade tumors in 60-70% of mice. Molecular analysis of TRIM24
      iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature,
      alongside increased glucose uptake and activated aerobic glycolysis.
      Collectively, these results identify a role for TRIM24 in breast tumorigenesis
      through reprogramming of glucose metabolism in HMECs, further supporting TRIM24
      as a viable therapeutic target in breast cancer. 

PMID- 25065591
TI  - Crumbs interacts with Xpd for nuclear division control in Drosophila.
AB  - Crumbs (Crb) family proteins are crucial for cell polarity. Recent studies
      indicate that they are also involved in growth regulation and cancer. However, it
      is not well-understood how Crb participates in mitotic processes. Here, we report
      that Drosophila Crb is critically involved in nuclear division by interacting
      with Xeroderma pigmentosum D (XPD). A novel gene named galla-1 was identified
      from a genetic screen for crb modifiers. Galla-1 protein shows homology to MIP18,
      a subunit of the mitotic spindle-associated MMS19-XPD complex. Loss-of-function
      galla-1 mutants show abnormal chromosome segregation, defective centrosome
      positions and branched spindles during nuclear division in early embryos. Embryos
      with loss-of-function or overexpression of crb show similar mitotic defects and
      genetic interaction with galla-1. Both Galla-1 and Crb proteins show overlapping
      localization with spindle microtubules during nuclear division. Galla-1
      physically interacts with the intracellular domain of Crb. Interestingly, Galla-1
      shows little binding to the Drosophila homolog of XPD, but a related protein
      Galla-2 binds both Crb and Xpd. Loss-of-function galla-2 mutants show similar
      mitotic defects as galla-1 and strong genetic interaction with crb. Xpd can form
      a physical complex with Crb. In imaginal disc, Crb overexpression causes tissue
      overgrowth as well as DNA damages marked by H2Av phosphorylation. These
      phenotypes are suppressed by reduction of Xpd. Taken together, this study
      identifies a novel Crb-Galla-Xpd complex and its function for proper chromosome
      segregation during nuclear division, implicating a potential link between Crb and
      Xpd-related genome instability. 

PMID- 25065592
TI  - Metabotropic glutamate receptor 1 acts as a dependence receptor creating a
      requirement for glutamate to sustain the viability and growth of human melanomas.
AB  - Metabotropic glutamate 1 (mGlu) receptor has been proposed as a target for the
      treatment of metastatic melanoma. Studies have demonstrated that inhibiting the
      release of glutamate (the natural ligand of mGlu1 receptors), results in a
      decrease of melanoma tumor growth in mGlu1 receptor-expressing melanomas. Here we
      demonstrate that mGlu1 receptors, which have been previously characterized as
      oncogenes, also behave like dependence receptors by creating a dependence on
      glutamate for sustained cell viability. In the mGlu1 receptor-expressing melanoma
      cell lines SK-MEL-2 (SK2) and SK-MEL-5 (SK5), we show that glutamate is both
      necessary and sufficient to maintain cell viability, regardless of underlying
      genetic mutations. Addition of glutamate increased DNA synthesis, whereas removal
      of glutamate not only suppressed DNA synthesis but also promoted cell death in
      SK2 and SK5 melanoma cells. Using genetic and pharmacological inhibitors, we
      established that this effect of glutamate is mediated by the activation of mGlu1
      receptors. The stimulatory potential of mGlu1 receptors was further confirmed in
      vivo in a melanoma cell xenograft model. In this model, subcutaneous injection of
      SK5 cells with short hairpin RNA-targeted downregulation of mGlu1 receptors
      resulted in a decrease in the rate of tumor growth relative to control. We also
      demonstrate for the first time that a selective mGlu1 receptor antagonist
      JNJ16259685 ((3,4-Dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4
      methoxycyclohexyl)-methanone) slows SK2 and SK5 melanoma tumor growth in vivo.
      Taken together, these data suggest that pharmacological inhibition of mGlu1
      receptors may be a novel approach for the treatment of metastatic melanoma. 

PMID- 25065593
TI  - Cyr61 silencing reduces vascularization and dissemination of osteosarcoma tumors.
AB  - Osteosarcoma is the most prevalent primary pediatric cancer-related bone disease.
      These tumors frequently develop resistance to chemotherapy and are highly
      metastatic, leading to poor outcome. Thus, there is a need for new therapeutic
      strategies that can prevent cell dissemination. We previously showed that
      CYR61/CCN1 expression in osteosarcoma cells is correlated to aggressiveness both
      in vitro and in vivo in mouse models, as well as in patients. In this study, we
      found that CYR61 is a critical contributor to the vascularization of primary
      tumor. We demonstrate that silencing CYR61, using lentiviral transduction, leads
      to a significant reduction in expression level of pro-angiogenic markers such as
      VEGF, FGF2, PECAM and angiopoietins concomitantly to an increased expression of
      major anti-angiogenic markers such as thrombospondin-1 and SPARC. Matrix
      metalloproteinase-2 family member expression, a key pathway in osteosarcoma
      metastatic capacity was also downregulated when CYR61 was downregulated in
      osteosarcoma cells. Using a metastatic murine model, we show that CYR61 silencing
      in osteosarcoma cells results in reduced tumor vasculature and slows tumor growth
      compared with control. We also find that microvessel density correlates with lung
      metastasis occurrence and that CYR61 silencing in osteosarcoma cells limits the
      number of metastases. Taken together, our data indicate that CYR61 silencing can
      blunt the malignant behavior of osteosarcoma tumor cells by limiting primary
      tumor growth and dissemination process. 

PMID- 25065594
TI  - Differential in vivo tumorigenicity of diverse KRAS mutations in vertebrate
      pancreas: A comprehensive survey.
AB  - Somatic activation of the KRAS proto-oncogene is evident in almost all pancreatic
      cancers, and appears to represent an initiating event. These mutations occur
      primarily at codon 12 and less frequently at codons 13 and 61. Although some
      studies have suggested that different KRAS mutations may have variable oncogenic
      properties, to date there has been no comprehensive functional comparison of
      multiple KRAS mutations in an in vivo vertebrate tumorigenesis system. We
      generated a Gal4/UAS-based zebrafish model of pancreatic tumorigenesis in which
      the pancreatic expression of UAS-regulated oncogenes is driven by a ptf1a:Gal4
      VP16 driver line. This system allowed us to rapidly compare the ability of 12
      different KRAS mutations (G12A, G12C, G12D, G12F, G12R, G12S, G12V, G13C, G13D,
      Q61L, Q61R and A146T) to drive pancreatic tumorigenesis in vivo. Among fish
      injected with one of five KRAS mutations reported in other tumor types but not in
      human pancreatic cancer, 2/79 (2.5%) developed pancreatic tumors, with both
      tumors arising in fish injected with A146T. In contrast, among fish injected with
      one of seven KRAS mutations known to occur in human pancreatic cancer, 22/106
      (20.8%) developed pancreatic cancer. All eight tumorigenic KRAS mutations were
      associated with downstream MAPK/ERK pathway activation in preneoplastic
      pancreatic epithelium, whereas nontumorigenic mutations were not. These results
      suggest that the spectrum of KRAS mutations observed in human pancreatic cancer
      reflects selection based on variable tumorigenic capacities, including the
      ability to activate MAPK/ERK signaling. 

PMID- 25065595
TI  - Immune-dependent antineoplastic effects of cisplatin plus pyridoxine in non-small
      cell lung cancer.
AB  - cis-Diamminedichloroplatinum(II) (CDDP), which is mostly referred to as
      cisplatin, is a widely used antineoplastic. The efficacy of cisplatin can be
      improved by combining it with the vitamin B6 precursor pyridoxine. Here, we
      evaluated the putative synergistic interaction of CDDP with pyridoxine in the
      treatment of an orthotopic mouse model of non-small-cell lung cancer (NSCLC).
      CDDP and pyridoxine exhibited hyperadditive therapeutic effects. However, this
      synergy was only observed in the context of an intact immune system and
      disappeared when the otherwise successful drug combination was applied to the
      same NSCLC cancer implanted in the lungs of athymic mice (which lack T
      lymphocytes). Immunocompetent mice that had been cured from NSCLC by the combined
      regimen of CDDP plus pyridoxine became resistant against subcutaneous rechallenge
      with the same (but not with an unrelated) cancer cell line. In vitro, CDDP and
      pyridoxine did not only cause synergistic killing of NSCLC cells but also
      elicited signs of immunogenic cell death including an endoplasmic reticulum
      stress response and exposure of calreticulin at the surface of the NSCLC cells.
      NSCLC cells treated with CDDP plus pyridoxine in vitro elicited a protective
      anticancer immune response upon their injection into immunocompetent mice.
      Altogether, these results suggest that the combined regimen of cisplatin plus
      pyridoxine mediates immune-dependent antineoplastic effects against NSCLC. 

PMID- 25065596
TI  - In vivo quantitative phosphoproteomic profiling identifies novel regulators of
      castration-resistant prostate cancer growth.
AB  - Prostate cancer remains a leading cause of cancer-related mortality worldwide
      owing to our inability to treat effectively castration-resistant tumors. To
      understand the signaling mechanisms sustaining castration-resistant growth, we
      implemented a mass spectrometry-based quantitative proteomic approach and use it
      to compare protein phosphorylation in orthotopic xenograft tumors grown in either
      intact or castrated mice. This investigation identified changes in
      phosphorylation of signaling proteins such as MEK, LYN, PRAS40, YAP1 and PAK2,
      indicating the concomitant activation of several oncogenic pathways in castration
      resistant tumors, a notion that was confirmed by tumor transcriptome analysis.
      Further analysis demonstrated that the activation of mTORC1, PAK2 and the
      increased levels of YAP1 in castration-resistant tumors can be explained by the
      loss of androgen inhibitory actions. The analysis of clinical samples
      demonstrated elevated levels of PAK2 and YAP1 in castration-resistant tumors,
      whereas knockdown experiments in androgen-independent cells demonstrated that
      both YAP1 and PAK2 regulate cell colony formation and cell invasion activity.
      PAK2 also influenced cell proliferation and mitotic timing. Interestingly, these
      phenotypic changes occur in the absence of obvious alterations in the activity of
      AKT, MAPK or mTORC1 pathways, suggesting that PAK2 and YAP1 may represent novel
      targets for the treatment of castration-resistant prostate cancer. Pharmacologic
      inhibitors of PAK2 (PF-3758309) and YAP1 (Verteporfin) were able to inhibit the
      growth of androgen-independent PC3 xenografts. This work demonstrates the power
      of applying high-resolution mass spectrometry in the proteomic profiling of
      tumors grown in vivo for the identification of novel and clinically relevant
      regulatory proteins. 

PMID- 25065597
TI  - Stromal fibroblast-derived miR-409 promotes epithelial-to-mesenchymal transition
      and prostate tumorigenesis.
AB  - Tumor-stromal interaction is a dynamic process that promotes tumor growth and
      metastasis via cell-cell interaction and extracellular vesicles. Recent studies
      demonstrate that stromal fibroblast-derived molecular signatures can be used to
      predict disease progression and drug resistance. To identify the epigenetic role
      of stromal noncoding RNAs in tumor-stromal interactions in the tumor
      microenvironment, we performed microRNA profiling of patient cancer-associated
      prostate stromal fibroblasts isolated by laser capture dissection microscopy and
      in bone-associated stromal models. We found specific upregulation of miR-409-3p
      and miR-409-5p located within the embryonically and developmentally regulated
      DLK1-DIO3 (delta-like 1 homolog-deiodinase, iodothyronine 3) cluster on human
      chromosome 14. The findings in cell lines were further validated in human
      prostate cancer tissues. Strikingly, ectopic expression of miR-409 in normal
      prostate fibroblasts conferred a cancer-associated stroma-like phenotype and led
      to the release of miR-409 via extracellular vesicles to promote tumor induction
      and epithelial-to-mesenchymal transition in vitro and in vivo. miR-409 promoted
      tumorigenesis through repression of tumor suppressor genes such as Ras suppressor
      1 and stromal antigen 2. Thus, stromal fibroblasts derived miR-409-induced
      tumorigenesis, epithelial-to-mesenchymal transition and stemness of the
      epithelial cancer cells in vivo. Therefore, miR-409 appears to be an attractive
      therapeutic target to block the vicious cycle of tumor-stromal interactions that
      plagues prostate cancer patients. 

PMID- 25065598
TI  - Galpha12 gep oncogene deregulation of p53-responsive microRNAs promotes
      epithelial-mesenchymal transition of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive
      phenotype. Galpha12 gep oncogene product couples to G-protein-coupled receptors,
      whose ligand levels are frequently increased in tumor microenvironments. Here, we
      report Galpha12 overexpression in human HCC and the resultant induction of zinc
      finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation.
      Galpha12 expression was higher in HCC than surrounding non-tumorous tissue.
      Transfection of Huh7 cell with an activated mutant of Galpha12 (Galpha12QL)
      deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215
      clusters in the miRNome. cDNA microarray analyses disclosed the targets affected
      by Galpha12 gene knockout. An integrative network of miRNAs and mRNA changes
      enabled us to predict ZEB1 as a key molecule governed by Galpha12. Decreases of
      miR-200a/b, -192 and -215 by Galpha12 caused ZEB1 induction. The ability of
      Galpha12 to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun
      mediated mouse double minute 2 homolog induction, contributed to transcriptional
      deregulation of the miRNAs. Galpha12QL induced ZEB1 and other epithelial
      mesenchymal transition markers with fibroblastoid phenotype change. Consistently,
      transfection with miR-200b, -192 or -215 mimic prevented the ability of
      Galpha12QL to increase tumor cell migration/invasion. In xenograft studies,
      sustained knockdown of Galpha12 decreased the overall growth rate and average
      volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients,
      miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth
      advantage. In the HCC samples with higher Galpha12 level, a correlation existed
      in the comparison of relative changes of Galpha12 and ZEB1. In conclusion,
      Galpha12 overexpressed in HCC causes ZEB1 induction by deregulating p53
      responsive miRNAs, which may facilitate epithelial-mesenchymal transition and
      growth of liver tumor. These findings highlight the significance of Galpha12
      upregulation in liver tumor progression, implicating Galpha12 as an attractive
      therapeutic target. 

PMID- 25065600
TI  - Will zeolite-based catalysis be as relevant in future biorefineries as in crude
      oil refineries?

PMID- 25065599
TI  - Androgen-regulated microRNA-135a decreases prostate cancer cell migration and
      invasion through downregulating ROCK1 and ROCK2.
AB  - Androgen signaling, via the androgen receptor (AR), is crucial in mediating
      prostate cancer (PCa) initiation and progression. Identifying new downstream
      effectors of the androgens/AR pathway will allow a better understanding of these
      mechanisms and could reveal novel biomarkers and/or therapeutic agents to improve
      the rate of patient survival. We compared the microRNA expression profiles in
      androgen-sensitive LNCaP cells stimulated or not with 1 nM R1881 by performing a
      high-throughput reverse transcriptase-quantitative PCR and found that miR-135a
      was upregulated. After androgen stimulation, we showed that AR directly activates
      the transcription of miR-135a2 gene by binding to an androgen response element in
      the promoter region. Our findings identify miR-135a as a novel effector in
      androgens/AR signaling. Using xenograft experiments in chick embryos and adult
      male mice, we showed that miR-135a overexpression decreases in vivo invasion
      abilities of prostate PC-3 cells. Through in vitro wound-healing migration and
      invasion assays, we demonstrated that this effect is mediated through
      downregulating ROCK1 and ROCK2 expression, two genes that we characterized as miR
      135a direct target genes. In human surgical samples from prostatectomy, we
      observed that miR-135a expression was lower in tumoral compared with paired
      adjacent normal tissues, mainly in tumors classified with a high Gleason score
      (?8). Moreover, miR-135a expression is lower in invasive tumors, showing
      extraprostatic extension, as compared with intraprostatic localized tumors. In
      tumor relative to normal glands, we also showed a more frequently higher ROCK1
      protein expression determined using a semi-quantitative immunohistochemistry
      analysis. Therefore, in tumor cells, the lower miR-135a expression could lead to
      a higher ROCK1 protein expression, which could explain their invasion abilities.
      The highlighted relationship between miR-135a expression level and the degree of
      disease aggressiveness suggests that miR-135a may be considered as a prognostic
      marker in human PCa. 

PMID- 25065601
TI  - Activation of T-LAK-cell-originated protein kinase-mediated antioxidation
      protects against focal cerebral ischemia-reperfusion injury.
AB  - T-LAK-cell-originated protein kinase (TOPK), a MAPKK-like kinase, is crucial for
      neural progenitor cell proliferation; however, the function of TOPK and the
      molecular mechanism underlying cerebral ischemia-reperfusion injury remains
      unknown. Therefore, we investigated the role of TOPK in experimental stroke.
      Sprague-Dawley rats underwent transient middle cerebral artery occlusion (tMCAO)
      and reperfusion, and TOPK small interfering RNA (siRNA) was delivered by
      intracerebroventricular injection at the beginning of MCAO. After TOPK
      overexpression and H2O2 stimulation in PC12 neuronal cells, antioxidative
      proteins, apoptosis-related proteins and signal pathways were detected by western
      blot analysis, the levels of the peroxidation products (malondialdehyde and 3
      nitrotyrosine) were measured with ELISA. Phosphorylation of TOPK was increased in
      rat cortical neurons following tMCAO. TOPK overexpression in PC12 cells augmented
      levels of antioxidative proteins (peroxiredoxin 1 and 2, heme oxygenase 1 and
      manganese superoxide dismutase), as well as total superoxide dismutase activity,
      along with inhibition of malondialdehyde and 3-nitrotyrosine upon H2O2
      stimulation. TOPK overexpression increased cell viability and reduced expression
      of caspase 3 and caspase 12 in PC12 cells in response to H2O2 . The p-ERK level
      was increased by TOPK overexpression, and antioxidative protection afforded by
      TOPK was abolished by blocking the extracellular signal-regulated kinase pathway
      in PC12 cells. TOPK siRNA increased the infarct volume and reduced total
      superoxide dismutase activity in the cortex in vivo after MCAO. These data reveal
      that activating TOPK confers neuroprotection against focal cerebral ischemia
      reperfusion injury by antioxidative function, in part through activation of the
      extracellular signal-regulated kinase pathway.

PMID- 25065602
TI  - Neurophysiological correlates of autobiographical memory deficits in currently
      and formerly depressed subjects.
AB  - BACKGROUND: Individuals with major depressive disorder (MDD) tested in either the
      depressed (dMDD) or remitted phase (rMDD) recall fewer specific and more
      categorical autobiographical memories (AMs) compared to healthy controls (HCs).
      The current study aimed to replicate findings of AM overgenerality in dMDD or
      rMDD, and to elucidate differences in neurophysiological correlates of AM recall
      between these MDD samples and HCs. METHOD: Unmedicated participants who met
      criteria for the dMDD, rMDD or HC groups (n = 16/group) underwent functional
      magnetic resonance imaging (fMRI) while recalling AMs in response to emotionally
      valenced cue words. Control tasks involved generating examples from an assigned
      semantic category and counting the number of risers in a letter string. RESULTS:
      The results showed fewer specific and more categorical AMs in both MDD samples
      versus HCs; dMDDs and rMDDs performed similarly on these measures. The
      neuroimaging results showed differences between groups in the dorsomedial
      prefrontal cortex (DMPFC), lateral orbitofrontal cortex (OFC), anterior insula,
      inferior temporal gyrus and parahippocampus/hippocampus during specific AM recall
      versus example generation. During specific AM recall cued by positively valenced
      words, group differences were evident in the DMPFC, middle temporal gyrus,
      parahippocampus/hippocampus and occipital gyrus, whereas differences during
      specific AM recall cued by negatively valenced words were evident in the DMPFC,
      superior temporal gyrus and hippocampus. CONCLUSIONS: AM deficits exist in rMDDs,
      suggesting that these impairments constitute trait-like abnormalities in MDD. We
      also found distinct patterns of hemodynamic activity for each group as they
      recalled specific AMs, raising the possibility that each group used a partly
      unique strategy for self-referential focus during successful retrieval of
      specific memories.

PMID- 25065603
TI  - Invoking pairwise interactions in water-promoted Diels-Alder reactions by using
      ionic liquids as cosolvents.
AB  - Rate constants and derived activation parameters of organic reactions in aqueous
      media, in particular Diels-Alder reactions, are sensitive to the presence of
      cosolvents in water. To enhance the solubility window of water, we introduced
      ionic liquids as cosolvents in the aqueous Diels-Alder reaction between
      anthracene-9-carbinol and N-ethylmaleimide. The reactive potentials of the
      organic compounds are parameterized by using semi-empirical quantum chemical
      methods. The principle of Savage-Wood additivity of group interactions is used to
      quantify the pairwise group interactions among chemically inert ionic liquids and
      organic reactants, both at initial and transition states of the reaction. The
      present approach shows promise, as the use of simple calculations from easily
      available kinetic data can help researchers to understand the versatility of
      green ionic-liquid alternatives to volatile organic solvents. 

PMID- 25065604
TI  - Rapid sonosynthesis of N-doped nano TiO2 on wool fabric at low temperature:
      introducing self-cleaning, hydrophilicity, antibacterial/antifungal properties
      with low alkali solubility, yellowness and cytotoxicity.
AB  - Nano nitrogen-doped titanium dioxide was rapidly prepared by hydrolysis of
      titanium isopropoxide at 75-80 degrees C using in situ sonochemical synthesis by
      introducing ammonia. Various concentrations of titanium isopropoxide were
      examined to deposit nano nitrogen-doped titanium dioxide through impregnation of
      the wool fabric in ultrasound bath followed by curing. The
      antibacterial/antifungal activities of wool samples were assessed against two
      common pathogenic bacteria including Escherichia coli and Staphylococcus aureus
      and the diploid fungus Candida albicans. The sonotreated wool fabrics indicated
      no adverse effects on human dermal fibroblasts. The presence of nanoparticles on
      the sonotreated wool fabrics were confirmed by FE-SEM images and EDS patterns and
      X-ray mapping and the crystalline size of nanoparticles were estimated through
      XRD results. The role of both pH and precursor concentration on the various
      properties of the fabric was investigated and the optimized conditions introduced
      using response surface methodology. 

PMID- 25065605
TI  - Evolution of volatile compounds and biogenic amines throughout the shelf life of
      marinated and salted anchovies (Engraulis encrasicolus).
AB  - Producers of processed anchovies have developed hazard analysis and critical
      control points (HACCP) to guarantee the quality of their products. Nonetheless
      there is a lack of objective data to determine products' shelf life. The quality
      of a product is usually established on the basis of its safety and organoleptic
      properties. These parameters were assessed by monitoring the profiles of volatile
      compounds and quantitating six biogenic amines in samples of two types of
      processed anchovies during their shelf life. With regard to biogenic amines,
      quantities were below the regulatory limits throughout shelf life, except when a
      temperature abuse was applied for marinated samples. Moreover, this work
      highlights an optimum volatile profile at 5 and 6 months of storage for salted
      and marinated anchovies, respectively. This is the result of a higher content of
      six aldehyde and nine ketone compounds, mainly from lipid oxidation. 

PMID- 25065606
TI  - Prevalence of Beauveria pseudobassiana among entomopathogenic fungi isolated from
      the hard tick, Ixodes ricinus.
AB  - Human and animal disease-transmitting hard ticks (Acari: Ixodidae) are of great
      concern for public health and animal farming. Alternatives to tick control by
      chemical acaricides are urgently needed, and one intensively evaluated biocontrol
      strategy is based on the use of tick-pathogenic filamentous fungi. An
      indispensable prerequisite for the development of tick-derived fungal isolates
      into registered myco-acaricides is their sound taxonomic characterisation. A set
      of fungal strains isolated from ixodid ticks in the Republic of Moldova was
      genetically characterised at the genus and species level together with further
      tick-derived fungal isolates from different geographic locations in Europe and
      North America. In a previous study, the same isolates had been assigned to the
      species Beauveria bassiana. Using a recent molecular taxonomic approach based on
      phylogenetic reconstruction from both internal transcribed spacer (ITS) and
      protein-encoding gene sequences, all fungi investigated were conclusively
      assigned to one of the two "hyphomycete" genera, Beauveria or Isaria (Ascomycota;
      Hypocreales; Cordycipitaceae). Within the genus Isaria, two species, Isaria
      farinosa and Isaria fumosorosea, were equally represented. Within the genus
      Beauveria, the comparatively rare species Beauveria pseudobassiana was found to
      strongly prevail among the isolates from Moldova, and one of the two tick-derived
      Beauveria strains from North America could be assigned to this species as well.
      In particular, the previous classification as B. bassiana could not be confirmed
      for any of the characterised tick pathogens from Europe and North America. The
      data presented here lend support to the hypothesis that within the genus
      Beauveria specific adaptation to ticks might have occurred within the species B.
      pseudobassiana. To test this hypothesis, a more extensive molecular taxonomic
      survey carefully reconsidering previous taxonomic assignments of tick-derived
      fungal isolates is needed. 

PMID- 25065607
TI  - Redirection of metabolic flux for high levels of omega-7 monounsaturated fatty
      acid accumulation in camelina seeds.
AB  - Seed oils enriched in omega-7 monounsaturated fatty acids, including palmitoleic
      acid (16:1?9) and cis-vaccenic acid (18:1?11), have nutraceutical and industrial
      value for polyethylene production and biofuels. Existing oilseed crops accumulate
      only small amounts (<2%) of these novel fatty acids in their seed oils. We
      demonstrate a strategy for enhanced production of omega-7 monounsaturated fatty
      acids in camelina (Camelina sativa) and soybean (Glycine max) that is dependent
      on redirection of metabolic flux from the typical ?9 desaturation of stearoyl
      (18:0)-acyl carrier protein (ACP) to ?9 desaturation of palmitoyl (16:0)-acyl
      carrier protein (ACP) and coenzyme A (CoA). This was achieved by seed-specific co
      expression of a mutant ?9-acyl-ACP and an acyl-CoA desaturase with high
      specificity for 16:0-ACP and CoA substrates, respectively. This strategy was most
      effective in camelina where seed oils with ~17% omega-7 monounsaturated fatty
      acids were obtained. Further increases in omega-7 fatty acid accumulation to 60
      65% of the total fatty acids in camelina seeds were achieved by inclusion of seed
      specific suppression of 3-keto-acyl-ACP synthase II and the FatB 16:0-ACP
      thioesterase genes to increase substrate pool sizes of 16:0-ACP for the ?9-acyl
      ACP desaturase and by blocking C18 fatty acid elongation. Seeds from these lines
      also had total saturated fatty acids reduced to ~5% of the seed oil versus ~12%
      in seeds of nontransformed plants. Consistent with accumulation of
      triacylglycerol species with shorter fatty acid chain lengths and increased
      monounsaturation, seed oils from engineered lines had marked shifts in
      thermotropic properties that may be of value for biofuel applications. 

PMID- 25065608
TI  - Conjugated bilirubin triggers anemia by inducing erythrocyte death.
AB  - Hepatic failure is commonly associated with anemia, which may result from
      gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such
      as infection and alcohol intoxication. At least in theory, anemia during hepatic
      failure may result from accelerated clearance of circulating erythrocytes. Here
      we show that bile duct ligation (BDL) in mice leads to severe anemia despite
      increased reticulocyte numbers. Bilirubin stimulated suicidal death of human
      erythrocytes. Mechanistically, bilirubin triggered rapid Ca(2+) influx,
      sphingomyelinase activation, formation of ceramide, and subsequent translocation
      of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro
      and in vivo findings, incubation of erythrocytes in serum from patients with
      liver disease induced suicidal death of erythrocytes in relation to their plasma
      bilirubin concentration. Consistently, patients with hyperbilirubinemia had
      significantly lower erythrocyte and significantly higher reticulocyte counts
      compared to patients with low bilirubin levels. CONCLUSION: Bilirubin triggers
      suicidal erythrocyte death, thus contributing to anemia during liver disease.

PMID- 25065610
TI  - Solution-processible brilliantly luminescent Eu(III) complexes with host-featured
      phosphine oxide ligands for monochromic red-light-emitting diodes.
AB  - A series of solution-processible electroluminescent (EL) Eu(3+) complexes were
      constructed with a self-host strategy, in which neutral ligands were employed as
      functionalized bidentate phosphine oxide (PO) ligands named DPEPOArn (DPEPO =
      bis(2-(diphenylphosphino)phenyl) ether oxide). The solubility of these complexes
      was dramatically improved owing to the increased ratios of organic components.
      This further enhanced the antenna effect of these ligands in both singlet and
      triplet energy-transfer processes to support high photoluminescent quantum yields
      (PLQYs) up to 86 % for their Eu(3+) complexes, which is outstanding among
      conjugated Eu(3+) complexes. Density function theory (DFT) simulations and
      electrochemical analysis further verified the contributions of DPEPOArn to the
      carrier injecting/transporting ability of the complexes. In this sense, these
      functionalized PO ligands served as hosts in optoelectronic processes, which
      rendered the self-host feature of their Eu(3+) complexes. With the enhanced
      electrical properties, the spin-coated single-layer organic light-emitting diodes
      (OLEDs) of these complexes achieved improved low driving voltages, such as onset
      voltages about 6 V, compared to their Eu(3+)-contained red-emitting polymeric
      analogues. [Eu(DBM)3DPEPODPNA2] (DBM = 1,3-diphenylpropane-1,3-dione, DPNA =
      diphenylnaphthylamine) with the most enhanced electrical properties and suitable
      frontier molecular orbital (FMO) and triplet state locations endowed its devices
      with the biggest maximum luminance of >90 cd m(-2) and the highest EL
      efficiencies. This work verified the potential of small molecular EL Eu(3+)
      complexes for solution-processed OLEDs through rational function integrations.

PMID- 25065609
TI  - Cigarette smoking and drug use among a nationally representative sample of HIV
      positive individuals.
AB  - BACKGROUND AND OBJECTIVES: Among HIV-positive populations, the prevalence of
      cigarette smoking remains disproportionately high and is associated with
      significant morbidity and mortality. Little is known about this topic among HIV
      positive persons in the general population. METHODS: Data came from the 2005 to
      2011 National Survey on Drug Use and Health (NSDUH) public use data files.
      Unadjusted and adjusted multinomial logistic regression analyses explored the
      associations between socio-demographic, drug and alcohol use, and drug and/or
      alcohol treatment characteristics with smoking status among HIV-positive
      individuals (n = 349). RESULTS: More than 40% of the sample was current smokers.
      In adjusted analyses, females (aRRR = .11, 95% CI = .03-.41) and participants who
      had never been married (aRRR = .19, 95% CI = .05-.58), were more likely to be
      former smokers than never smokers. Females (aRRR = .37, 95% CI = .14-.96) and
      individuals older than age 35 (aRRR = .37, 95% CI = .16-.89) were less likely to
      be current smokers than never smokers. Conversely, previously married persons
      (aRRR = 5.72, 95% CI = 1.40-23.31), participants reporting binge drinking (aRRR =
      5.96, 95% CI = 2.27-15.64), and lifetime drug or alcohol treatment (aRRR = 5.12,
      95% CI = 2.09-12.55) were more likely to be current smokers than never smokers.
      CONCLUSIONS: Findings help confirm the high prevalence of smoking among HIV
      positive persons suggesting the need for integrated substance use and smoking
      cessation treatment among HIV-positives. SCIENTIFIC SIGNIFICANCE: The present
      findings have implications for the development and implementation of targeted
      smoking cessation programs for HIV-positive smokers.

PMID- 25065611
TI  - Marek's disease virus influences the core gut microbiome of the chicken during
      the early and late phases of viral replication.
AB  - Marek's disease (MD) is an important neoplastic disease of chickens caused by the
      Marek's disease virus (MDV), an oncogenic alphaherpesvirus. In this study,
      dysbiosis induced by MDV on the core gut flora of chicken was assessed using next
      generation sequence (NGS) analysis. Total fecal and cecum-derived samples from
      individual birds were used to estimate the influence of MDV infection on the gut
      microbiome of chicken. Our analysis shows that MDV infection alters the core gut
      flora in the total fecal samples relatively early after infection (2-7 days) and
      in the late phase of viral infection (28-35 days) in cecal samples, corresponding
      well with the life cycle of MDV. Principle component analyses of total fecal and
      cecal samples showed clustering at the early and late time points, respectively.
      The genus Lactobacillus was exclusively present in the infected samples in both
      total fecal and cecal bird samples. The community colonization of core gut flora
      was altered by viral infection, which manifested in the enrichment of several
      genera during the early and late phases of MDV replication. The results suggest a
      relationship between viral infection and microbial composition of the intestinal
      tract that may influence inflammation and immunosuppression of T and B cells in
      the host.

PMID- 25065612
TI  - Amorphous molybdenum sulfides as hydrogen evolution catalysts.
AB  - Providing energy for a population projected to reach 9 billion people within the
      middle of this century is one of the most pressing societal issues. Burning
      fossil fuels at a rate and scale that satisfy our near-term demand will
      irreversibly damage the living environment. Among the various sources of
      alternative and CO2-emission-free energies, the sun is the only source that is
      capable of providing enough energy for the whole world. Sunlight energy, however,
      is intermittent and requires an efficient storage mechanism. Sunlight-driven
      water splitting to make hydrogen is widely considered as one of the most
      attractive methods for solar energy storage. Water splitting needs a hydrogen
      evolution catalyst to accelerate the rate of hydrogen production and to lower the
      energy loss in this process. Precious metals such as Pt are superior catalysts,
      but they are too expensive and scarce for large-scale applications. In this
      Account, we summarize our recent research on the preparation, characterization,
      and application of amorphous molybdenum sulfide catalysts for the hydrogen
      evolution reaction. The catalysts can be synthesized by electrochemical
      deposition under ambient conditions from readily available and inexpensive
      precursors. The catalytic activity is among the highest for nonprecious
      catalysts. For example, at a loading of 0.2 mg/cm(2), the optimal catalyst
      delivers a current density of 10 mA/cm(2) at an overpotential of 160 mV. The
      growth mechanism of the electrochemically deposited film catalysts was revealed
      by an electrochemical quartz microcrystal balance study. While different
      electrochemical deposition methods produce films with different initial
      compositions, the active catalysts are the same and are identified as a
      "MoS(2+x)" species. The activity of the film catalysts can be further promoted by
      divalent Fe, Co, and Ni ions, and the origins of the promotional effects have
      been probed. Highly active amorphous molybdenum sulfide particles can also be
      prepared from simple wet-chemical routes. Electron transport is sometimes slow in
      the particle catalysts, and an impedance model has been established to identify
      this slow electron transport. Finally, the amorphous molybdenum sulfide film
      catalyst has been integrated onto a copper(I) oxide photocathode for
      photoelectrochemical hydrogen evolution. The conformal catalyst efficiently
      extracts the excited electrons to give an impressive photocurrent density of -5.7
      mA/cm(2) at 0 V vs RHE. The catalyst also confers good stability.

PMID- 25065613
TI  - Intra-dialytic exercise training: a pragmatic approach.
AB  - This continuing education paper outlines the skills and knowledge required to
      plan, implement and evaluate a pragmatic approach to intra-dialytic exercise
      training. AIM: The aim of this continuing education article is to enable the
      nephrology multi-disciplinary team (MDT) to plan, implement and evaluate the
      provision of intra-dialytic exercise training for patients receiving
      haemodialysis therapy. LEARNING OUTCOMES: After reading this article the reader
      should be able to: Appreciate the level of evidence base for the clinical
      effectiveness of renal exercise rehabilitation and locate credible sources of
      research and educational information Understand and consider the need for
      appropriate evaluation and assessment outcomes as part of a renal rehabilitation
      plan Understand the components of exercise programming and prescription as part
      of an integrated renal rehabilitation plan Develop a sustainable longer term
      exercise and physical activity plan.

PMID- 25065614
TI  - The effects on children of depressed mothers' remission and relapse over 9
      months.
AB  - BACKGROUND: The high rate of depression among children of depressed mothers is
      well known. Suggestions that improvement in maternal acute depression has a
      positive effect on the child have emerged. However, data on the mechanisms of
      change have been sparse. The aim was to understand how remission and relapse in
      the mother might explain the changes in the child's outcome. METHOD: Participants
      were 76 depressed mothers who entered into a medication clinical trial for
      depression and 135 of their eligible offspring ages 7-17 years. The mothers and
      children were assessed at baseline and periodically over 9 months by independent
      teams to understand the relationship between changes in children's symptoms and
      functioning and maternal remission or relapse. The main outcome measures were,
      for mothers, the Hamilton Depression Rating Scale (HAMD), the Social Adjustment
      Scale (SAS) and the Parental Bonding Instrument (PBI) and, for children, the
      Children's Depression Inventory (CDI), the Columbia Impairment Scale (CIS), the
      Multidimensional Anxiety Scale for Children (MASC) and the Children's Global
      Assessment Scale (CGAS). RESULTS: Maternal remission was associated with a
      decrease in the child's depressive symptoms. The mother's subsequent relapse was
      associated with an increase in the child's symptoms over 9 months. The effect of
      maternal remission on the child's improvement was partially explained by an
      improvement in the mother's parenting, particularly the change in the mother's
      ability to listen and talk to her child, but also reflected in her improvement in
      parental bonding. These findings could not be explained by the child's treatment.
      CONCLUSIONS: A depressed mother's remission is associated with her improvement in
      parenting and a decrease in her child's symptoms. Her relapse is associated with
      an increase in her child's symptoms.

PMID- 25065615
TI  - The application of multiple biophysical cues to engineer functional neocartilage
      for treatment of osteoarthritis. Part II: signal transduction.
AB  - The unique mechanoelectrochemical environment of cartilage has motivated
      researchers to investigate the effect of multiple biophysical cues, including
      mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is
      well established that biophysical stimuli promote chondrocyte proliferation,
      differentiation, and maturation within "biological windows" of defined dose
      parameters, including mode, frequency, magnitude, and duration of stimuli (see
      companion review Part I: Cellular Response). However, the underlying molecular
      mechanisms and signal transduction pathways activated in response to multiple
      biophysical stimuli remain to be elucidated. Understanding the mechanisms of
      biophysical signal transduction will deepen knowledge of tissue organogenesis,
      remodeling, and regeneration and aiding in the treatment of pathologies such as
      osteoarthritis. Further, this knowledge will provide the tissue engineer with a
      potent toolset to manipulate and control cell fate and subsequently develop
      functional replacement cartilage. The aim of this article is to review
      chondrocyte signal transduction pathways in response to mechanical, magnetic, and
      electrical cues. Signal transduction does not occur along a single pathway;
      rather a number of parallel pathways appear to be activated, with calcium
      signaling apparently common to all three types of stimuli, though there are
      different modes of activation. Current tissue engineering strategies, such as the
      development of "smart" functionalized biomaterials that enable the delivery of
      growth factors or integration of conjugated nanoparticles, may further benefit
      from targeting known signal transduction pathways in combination with external
      biophysical cues. 

PMID- 25065616
TI  - The prediction of MRI for the possibility of regression of herniated nucleus
      pulposus.

PMID- 25065617
TI  - Anatomical significance in aortoiliac occlusive disease.
AB  - Aortoiliac occlusive disease is a subset of peripheral arterial disease involving
      an atheromatous occlusion of the infrarenal aorta, common iliac arteries, or
      both. The disease, as it is known today, was described by the French surgeon Rene
      Leriche as a thrombotic occlusion of the end of the aorta. Leriche successfully
      linked the anatomic location of the occlusion with a unique triad of symptoms,
      including claudication, impotence, and decreased peripheral pulses. The
      anatomical location of the atheromatous lesions also has a direct influence on
      classification of the disease, as well as choice of treatment modality.
      Considering its impact on diagnosis and treatment, we aimed to provide a detailed
      understanding of the anatomical structures involved in aortoiliac occlusive
      disease. Familiarity with these structures will aid the physician in
      interpretation of radiologic images and surgical planning.

PMID- 25065618
TI  - Hepatic expression of miR-122, miR-126, miR-136 and miR-181a and their
      correlation to histopathological and clinical characteristics of patients with
      hepatitis C.
AB  - It has been shown for hepatitis C virus (HCV) infection that host miRNAs
      contribute to the replication of the viral RNA genome. However, the clinical
      impact of these and many other cellular miRNAs on HCV in humans is still largely
      unclear. We therefore analysed the expression of miR-122, miR-126, miR-181a and
      miR-136 in HCV-infected patients. The study included liver biopsies of 65
      patients infected with HCV of different genotypes (gt 1, gt 1a, gt 1b, gt 3 and
      gt 4) and nine noninfected individuals. Expression analysis of miRNAs was
      performed by qPCR, and they were analysed for differences between patient gender
      and age, genotypes, stage of fibrosis, grade of inflammation, serum level of
      liver enzymes, serum viral load, the presence of steatosis and mode of
      transmission. Different target prediction algorithms were used to search for
      targets of analyzed miRNAs. Statistical analysis revealed significant up
      regulation of miR-136 and down-regulation of miR-126 and miR-181a in patients
      infected with HCV of different genotypes compared with noninfected individuals.
      The same expression pattern was observed in different stages and grades of liver
      disease. miR-122 was up-regulated in women relative to men and associated to
      portal inflammation, miR-122 and miR-126 correlated with serum HCV load and miR
      136 and miR-122 correlated with the presence of steatosis. miR-126 and miR-136
      were differentially expressed between different modes of HCV transmission. There
      were approximately 2000 different targets predicted for all four miRNAs and each
      of the analyzed miRNAs could be involved in more than a 100 different biochemical
      pathways. miR-122, miR-126, miR-136 and miR-181a have been shown to be involved
      in HCV infection with different genotypes. Their expression has been associated
      with the gender, stage and grade of liver disease, mode of transmission, serum
      HCV load and the presence of steatosis. Numerous target genes and biochemical
      pathways are predicted for each of the analyzed miRNAs. All these results suggest
      their role in HCV-infected liver disease. 

PMID- 25065620
TI  - Maternal medical compromise during pregnancy and pregnancy outcomes.
AB  - OBJECTIVE: To examine the outcomes of pregnancy and newborn following an event of
      maternal medical compromise during pregnancy. METHODS: A retrospective study was
      performed on all patients hospitalized following an event of medical compromise
      during pregnancy. Medical compromise was divided to acute or chronic bleeding,
      major or complicated operations, and admission to intensive care unit (ICU). Data
      collected included maternal, fetal, neonatal and child's follow-up. RESULTS: The
      study included 51 pregnant patients and 58 fetuses. The study group had increased
      risk of preterm deliveries (35.0 versus 6.5%, p < 0.001), cesarean delivery (55.0
      versus 22.7%, p < 0.001) and low Apgar scores (5.0 versus 0.45%, p = 0.002).
      Patients with acute bleeding had higher rates of cesarean sections, preterm
      deliveries, admissions to neonatal ICU and neonatal mortality. Two cases of fetal
      abnormalities included brain abnormalities and pericardial effusion. Three
      terminations of pregnancies were performed: two in patients in ICU due to severe
      maternal medical condition and one in the fetus with brain abnormalities.
      CONCLUSIONS: Maternal medical compromise during pregnancy increases the risk for
      preterm deliveries, cesarean delivery and low Apgar scores. Acute bleeding was
      the main cause of medical compromised and with the higher rates of adverse
      outcomes.

PMID- 25065621
TI  - Surfactant administration without intubation in preterm infants with respiratory
      distress syndrome--our experiences.
AB  - BACKGROUND: Surfactant replacement therapy is crucial in the management of
      respiratory distress syndrome (RDS) in preterm infants. Classic strategies of
      surfactant administration required intubation. To reduce the need of intubation
      and mechanical ventilation (MV), we applied surfactant via a thin endotracheal
      catheter without intubation. PATIENTS AND METHODS: We compared 26 preterm infants
      threatened by RDS treated with surfactant via a thin endotracheal catheter
      without intubation (studied group - SG) with a retrospective group of preterm
      infants managed on MV with early surfactant treatment using INtubation SURfactant
      Extubation (INSURE) method (control group - CG). Study had an approval from the
      ethics committee (RNN/6/14/KE). RESULTS: In the SG, 26 preterm infants were
      treated with one dose of surfactant (Curosurf(r)) administered via endotracheal
      catheter without intubation while receiving nasal continuous positive airway
      pressure (nCPAP)/SiPAP (Infant Flow). After surfactant administration,
      significantly less patients in SG required intubation and MV (19.2%) versus 65%
      necessity of second intubation in the CG. The median of time of MV in SG was 5 d
      versus 3.5 d in CG. Median time spent on nCPAP was 5.5 d versus 4.0 d in CG. The
      incidence of intraventricular hemorrhage (IVH) in the SG was 53.9%, including 50%
      with >= IVH II versus 36.7% (30% >= IVH II) in CG. The incidence of other
      complications of prematurity in the SG, such as necrotizing enterocolitis was
      11.5% versus 23.3% in CG, the hemodynamically important patent ductus arteriosus
      was observed in 53.9% in SG versus 45% in CG. Bronchopulmonary dysplasia level in
      SG was significantly lower (15.4%) than in CG (40%), and the incidence of
      retinopathy of prematurity in SG was also lower (3.9%) versus 11.7% in MV group.
      CONCLUSION: Surfactant application via a thin endotracheal catheter without
      intubation seems to be a beneficial therapy for preterm infants with slight and
      mild degree of RDS. This new method of surfactant application was associated with
      a lower prevalence of intubation and MV and better pulmonary outcome than
      implementation of traditional surfactant therapy (INSURE) and MV. Prospective
      randomized controlled trial is required.

PMID- 25065624
TI  - Effect of hirulog-like peptide on middle cerebral artery occlusion-induced brain
      injury in mice.
AB  - Hirulog-like peptide (HLP) and low-molecular-weight heparin (LMWH) are thrombin
      inhibitor peptides. Our previous study demonstrated that HLP could reduce
      vascular neointimal formation or restenosis in animals undergoing balloon
      catheter injury in the carotid artery. However, the function of HLP during
      ischemic stroke is largely unknown. The present study investigated the effect of
      HLP on brain injury, which was induced by suture of middle cerebral artery
      occlusion in mice. Mice were divided into four groups, which included a sham
      group and three treatment groups. Ischemia was induced by transient suture
      insertion into the middle cerebral artery for 90 min, and mice were either
      treated with saline, HLP or LMWH. Infarct volume, neurologic deficits and
      apoptotic factors were measured following 1-14 days of ischemia. We demonstrated
      that HLP intravenous injection alleviated brain infarct volume and improved
      neurologic outcomes (p<0.05). HLP decreased levels of protease-activated receptor
      1 (PAR-1), caspase-3, malondialdehyde (MDA) and Bcl-2-associated X protein (Bax),
      increased the activities of catalase and B cell lymphoma-2 (Bcl-2), and improved
      the ratio of Bcl-2/Bax compared with the control (p<0.05). This study indicates
      that HLP and LMWH reduced infarct volume and improved neurobehavioral outcomes
      induced by transient middle cerebral artery occlusion (tMCAO). In addition, HLP
      had a beneficial effect on the regulation of the thrombin receptor and key
      apoptosis regulators in the mouse brain. These results suggest that HLP may be a
      potential alternative therapy for arterial occlusion-induced cerebral ischemia.

PMID- 25065622
TI  - Galectin-9-CD44 interaction enhances stability and function of adaptive
      regulatory T cells.
AB  - The beta-galactoside-binding protein galectin-9 is critical in regulating the
      immune response, but the mechanism by which it functions remains unclear. We have
      demonstrated that galectin-9 is highly expressed by induced regulatory T cells
      (iTreg) and was crucial for the generation and function of iTreg cells, but not
      natural regulatory T (nTreg) cells. Galectin-9 expression within iTreg cells was
      driven by the transcription factor Smad3, forming a feed-forward loop, which
      further promoted Foxp3 expression. Galectin-9 increased iTreg cell stability and
      function by directly binding to its receptor CD44, which formed a complex with
      transforming growth factor-beta (TGF-beta) receptor I (TGF-betaRI), and activated
      Smad3. Galectin-9 signaling was further found to regulate iTreg cell induction by
      dominantly acting through the CNS1 region of the Foxp3 locus. Our data suggest
      that exogenous galectin-9, in addition to being an effector molecule for Treg
      cells, acts synergistically with TGF-beta to enforce iTreg cell differentiation
      and maintenance.

PMID- 25065623
TI  - Symbiotic bacterial metabolites regulate gastrointestinal barrier function via
      the xenobiotic sensor PXR and Toll-like receptor 4.
AB  - Intestinal microbial metabolites are conjectured to affect mucosal integrity
      through an incompletely characterized mechanism. Here we showed that microbial
      specific indoles regulated intestinal barrier function through the xenobiotic
      sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context
      of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF
      alpha while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2(
      /-)) mice showed a distinctly "leaky" gut physiology coupled with upregulation of
      the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial
      barrier were corrected in Nr1i2(-/-)Tlr4(-/-) mice. Our results demonstrate that
      a direct chemical communication between the intestinal symbionts and PXR
      regulates mucosal integrity through a pathway that involves luminal sensing and
      signaling by TLR4.

PMID- 25065626
TI  - Reply to letter on published paper: improving quality of care in inflammatory
      bowel disease: what changes can be made today?

PMID- 25065625
TI  - Visual cues and gait improvement in Parkinson's disease: which piece of
      information is really important?
AB  - Visual exproprioception refers to information of the body relative to the
      environment and may be the critical piece of sensory information that explains
      why gait improvements can be achieved with visual step cues in people with
      Parkinson's disease (PD). The primary aim of current study was to investigate the
      role of visual exproprioception in the positive effect of visual cues on gait in
      patients with PD. Nineteen individuals with PD and 15 healthy subjects
      participated in this study. Four conditions of self-paced gait were tested:
      normal walking, without exproprioception (exproprioceptive information of lower
      limbs removed), visual step length cues, and visual step length cues but without
      exproprioception. Gaze behavior, gait parameters and the accuracy and precision
      of foot placement on the visual cues were recorded. Individuals with PD improved
      step length in both cued conditions. Both groups fixated close to 46% on visual
      cues necessary to accomplish the next step (ongoing step), while 54% of fixations
      were focused on visual cues one or more steps ahead. Also, both groups increased
      absolute error and error variability of the foot placement around the visual cues
      without vision of their feet. These results suggest that exproprioceptive
      information is not critical to achieve step length and overall gait benefits with
      visual cues in PD, but is critical for the accuracy and precision of foot
      placement on targets. People with PD and healthy individuals use visual
      information from visual cues in both on-line and feedforward fashions. In
      conclusion, patients with PD likely focus attention on the discrete goal of each
      foot hitting a visual cue placed on the floor and then use the exteroceptive
      information (i.e. position of next foot placement location) to plan each step
      individually at a cortical level. 

PMID- 25065627
TI  - Overground versus self-paced treadmill walking in a virtual environment in
      children with cerebral palsy.
AB  - Treadmill walking offers several advantages for clinical gait analysis and gait
      training, but may affect gait parameters. We compared walking on a self-paced
      treadmill in a virtual environment (TM+) with overground walking in a
      conventional gait lab (CGL), and with natural walking (NW) outside a lab
      environment on a GaitRite measurement mat, for 11 typically developing (TD)
      children and 9 children with cerebral palsy (CP). Spatiotemporal parameters and
      subjective scores on similarity to normal walking were compared between all three
      conditions, while kinematic parameters and Gait and Motion Analysis Profile
      Scores (GPS and MAP) were compared between CGL and TM+. Subjects walked slower
      and with shorter strides in both lab conditions compared to NW. Stride width was
      3-4 cm wider in TM+ than in CGL and NW. Mean kinematic curves showed a few
      differences between CGL and TM+: on the treadmill children with CP walked with on
      average 2 degrees  more pelvic tilt, 7 degrees  more knee flexion at initial
      contact, and more deviating knee and ankle kinematics as indicated by the MAP
      scores. These differences may in part be due to increased fatigue in TM+ as a
      result of longer continuous walking time. Our results indicate that differences
      between self-paced treadmill walking in a VR and walking in a conventional gait
      lab are generally small, but need to be taken into account when performing gait
      analysis on a treadmill.

PMID- 25065628
TI  - Assessment of arm movements during gait in stroke - the Arm Posture Score.
AB  - The purpose of the study was to apply the Arm Posture Score (APS) to a stroke
      population, since comprehensive measures to quantify arm swing in the affected
      and non-affected arms during gait are lacking. A further aim was to investigate
      how gait speed and upper limb function estimated by clinical measures are related
      to the APS in the stroke group. The APS is the summarized root mean square
      deviation (RMSD) from normal, based on kinematics. Four arm movements (sagittal
      and frontal planes) as well as six arm movements (incorporating transversal
      plane) were included in the calculation of APS, referred to as APS4 and APS6,
      respectively. The study population consisted of 25 persons with stroke and 25 age
      and gender-matched controls. The APS measures were significantly different
      between the affected and non-affected arms, as well as between the affected arm
      and the non-dominant arm of the controls (p<=0.001). Spasticity significantly
      influenced both APS measures, while speed only had a significant effect on the
      APS4. The APS measures correlated significantly to clinical measures of upper
      limb function. Both APS measures seem to be useful indices to quantify and
      discriminate between impaired and normal arm swing during gait after stroke. The
      variability of rotational arm movements needs to be studied further before
      considering the additional value of the APS6 over the APS4. When interpreting the
      APS, complementary kinematics should be taken into account, as the single value
      of the APS gives no information about the direction of the deviation. 

PMID- 25065629
TI  - A data driven model for optimal orthosis selection in children with cerebral
      palsy.
AB  - A statistical orthosis selection model was developed using the Random Forest
      Algorithm (RFA). The model's performance and potential clinical benefit was
      evaluated. The model predicts which of five orthosis designs - solid (SAFO),
      posterior leaf spring (PLS), hinged (HAFO), supra-malleolar (SMO), or foot
      orthosis (FO) - will provide the best gait outcome for individuals with diplegic
      cerebral palsy (CP). Gait outcome was defined as the change in Gait Deviation
      Index (GDI) between walking while wearing an orthosis compared to barefoot
      (DeltaGDI=GDIOrthosis-GDIBarefoot). Model development was carried out using
      retrospective data from 476 individuals who wore one of the five orthosis designs
      bilaterally. Clinical benefit was estimated by predicting the optimal orthosis
      and DeltaGDI for 1016 individuals (age: 12.6 (6.7) years), 540 of whom did not
      have an existing orthosis prescription. Among limbs with an orthosis, the model
      agreed with the prescription only 14% of the time. For 56% of limbs without an
      orthosis, the model agreed that no orthosis was expected to provide benefit.
      Using the current standard of care orthosis (i.e. existing orthosis
      prescriptions), DeltaGDI is only +0.4 points on average. Using the orthosis
      prediction model, average DeltaGDI for orthosis users was estimated to improve to
      +5.6 points. The results of this study suggest that an orthosis selection model
      derived from the RFA can significantly improve outcomes from orthosis use for the
      diplegic CP population. Further validation of the model is warranted using data
      from other centers and a prospective study. 

PMID- 25065630
TI  - CoPc-catalyzed selective radical arylation of anilines with arylhydrazines for
      synthesis of 2-aminobiaryls.
AB  - CoPc-catalyzed selective radical arylation of anilines with arylhydrazines to
      afford 2-aminobiaryls in moderate to good yields is described. 

PMID- 25065631
TI  - Stimuli responsive chiral liquid crystal phases of phenylboronic acid
      functionalized rodlike viruses and their interaction with biologically important
      diols.
AB  - The rodlike M13 viruses with chemically decorated phenylboronic acid moieties
      form pH responsive chiral nematic liquid crystal (LC) phases. Binding with
      biologically important diols results in LC phases with microstructures that
      closely correlate with the molecular structure of the diols and can be
      conveniently discerned by visual cues. 

PMID- 25065632
TI  - Co-occurrence of psychotic experiences and common mental health conditions across
      four racially and ethnically diverse population samples.
AB  - BACKGROUND: Prior research with racially/ethnically homogeneous samples has
      demonstrated widespread co-occurrence of psychotic experiences (PEs) and common
      mental health conditions, particularly multi-morbidity, suggesting that psychosis
      may be related to the overall severity of psychiatric disorder rather than any
      specific subtype. In this study we aimed to examine whether PEs are associated
      with the presence of specific disorders or multi-morbidity of co-occurring
      disorders across four large racially/ethnically diverse samples of adults in the
      USA. METHOD: Data were drawn from the National Comorbidity Survey Replication
      (NCS-R), the National Survey of American Life (NSAL) and separately from the
      Asian and Latino subsamples of the National Latino and Asian American Study
      (NLAAS). Logistic regression models were used to examine the relationship between
      PEs and individual subtypes of DSM-IV disorder, and to test for a linear dose
      response relationship between the number of subtypes and PEs. RESULTS: Prevalence
      of PEs was moderately greater among individuals with each subtype of disorder in
      each data set [odds ratios (ORs) 1.8-3.8], although associations were only
      variably significant when controlling for clinical and demographic variables.
      However, the sum of disorder subtypes was related to odds for PEs in a linear
      dose-response fashion across all four samples. CONCLUSIONS: PEs are related
      primarily to the extent or severity of psychiatric illness, as indicated by the
      presence of multiple psychiatric disorders, rather than to any particular subtype
      of disorder in these data. This relationship applies to the general population
      and across diverse racial/ethnic groups.

PMID- 25065633
TI  - Development of a soft-sensor based on multi-wavelength fluorescence spectroscopy
      and a dynamic metabolic model for monitoring mammalian cell cultures.
AB  - A soft-sensor based on an Extended Kalman Filter (EKF) that combines data
      obtained using a fluorescence-based soft-sensor with a dynamic mechanistic model,
      was investigated as a tool for continuous monitoring of a Chinese hamster ovary
      (CHO) cell cultivation process. A standalone fluorescence based soft-sensor,
      which uses a combination of an empirical multivariate statistical model and
      measured spectra, was designed for predicting key culture variables including
      viable and dead cells, recombinant protein, glucose, and ammonia concentrations.
      The standalone fluorescence sensor was then combined with a dynamic mechanistic
      model within an EKF framework, for improving the prediction accuracy and
      generating predictions in-between sampling instances. The dynamic model used for
      the EKF framework was based on a structured metabolic flux analysis and mass
      balances. In order to calibrate the fluorescence-based empirical model and the
      dynamic mechanistic model, cells were grown in batch mode with different initial
      glucose and glutamine concentrations. To mitigate the uncertainty associated with
      the model structure and parameters, non-stationary disturbances were accounted
      for in the EKF by parameter-adaptation. It was demonstrated that the
      implementation of the EKF along with the dynamic model could improve the accuracy
      of the fluorescence-based predictions at the sampling instances. Additionally, it
      was shown that the major advantage of the EKF-based soft-sensor, compared to the
      standalone fluorescence-based counterpart, was its capability to track the
      temporal evolution of key process variables between measurement instances
      obtained by the fluorescence-based soft-sensor. This is crucial for designing
      control strategies of CHO cell cultures with the aim of guaranteeing product
      quality.

PMID- 25065634
TI  - Reference materials for cellular therapeutics.
AB  - The development of cellular therapeutics (CTP) takes place over many years, and,
      where successful, the developer will anticipate the product to be in clinical use
      for decades. Successful demonstration of manufacturing and quality consistency is
      dependent on the use of complex analytical methods; thus, the risk of process and
      method drift over time is high. The use of reference materials (RM) is an
      established scientific principle and as such also a regulatory requirement. The
      various uses of RM in the context of CTP manufacturing and quality are discussed,
      along with why they are needed for living cell products and the analytical
      methods applied to them. Relatively few consensus RM exist that are suitable for
      even common methods used by CTP developers, such as flow cytometry. Others have
      also identified this need and made proposals; however, great care will be needed
      to ensure any consensus RM that result are fit for purpose. Such consensus RM
      probably will need to be applied to specific standardized methods, and the idea
      that a single RM can have wide applicability is challenged. Written standards,
      including standardized methods, together with appropriate measurement RM are
      probably the most appropriate way to define specific starting cell types. The
      characteristics of a specific CTP will to some degree deviate from those of the
      starting cells; consequently, a product RM remains the best solution where
      feasible. Each CTP developer must consider how and what types of RM should be
      used to ensure the reliability of their own analytical measurements. 

PMID- 25065635
TI  - Purification of regulatory T cells with the use of a fully enclosed high-speed
      microfluidic system.
AB  - BACKGROUND AIMS: Despite promising advances in cellular therapies, it will be
      difficult to fully test or implement new therapies until advances are made in the
      processes for cell preparation. This study describes the use of an advanced
      prototype of a flow-cytometry cell purification system constructed for operation
      in a clinical environment to prepare regulatory T cells defined as
      CD4(+)/CD25(bright)/CD127(neg/low). METHODS: The sort performance of the Gigasort
      system was directly compared with available droplet sorters using mixtures of
      highly fluorescent and non-fluorescent 5-MUm polystyrene particles. CD4(+)
      enriched cell preparations were processed with the use of a sterile, disposable
      fluid handling unit with a chip containing parallel microfluidic-based sorters.
      RESULTS: Similar purity and sort efficiency as found with droplet sorters were
      obtained with the 24-channel chip sorter system. Starting with 450 million fresh
      peripheral blood mononuclear cells, 150,000 to 1.7 million cells that were, on
      average, 85% FoxP3-positive and 97% viable, were obtained in <4 h. CONCLUSIONS:
      This study presents a technology adapted to regulatory requirements for clinical
      cell purification and that achieves high throughput and cell-friendly conditions
      by use of a microfluidic chip with 24 parallel microsorters, providing a rapid,
      sterile method of purifying regulatory T cells accurately and with excellent
      viability.

PMID- 25065636
TI  - Proliferative and phenotypical characteristics of human adipose tissue-derived
      stem cells: comparison of Ficoll gradient centrifugation and red blood cell lysis
      buffer treatment purification methods.
AB  - BACKGROUND AIMS: Adult human subcutaneous adipose tissue harbors a multipotent
      stem cell population, the so-called human adipose tissue-derived mesenchymal
      stromal cells (AT-MSCs). These cells are able to differentiate in vitro into
      various cell types and possess immunomodulatory features. Yet procedures to
      obtain AT-MSCs can vary significantly. The two most extensively used AT-MSC
      purification techniques are (i) density gradient centrifugation using Ficoll and
      (ii) red blood cell (RBC) lysis buffer treatment of the stromal vascular
      fraction. In the context of potential clinical cell therapy, the stem cell yield
      after purification and upon consecutive passages, as well as the purity of the
      obtained cell population, are of utmost importance. METHODS: We investigated the
      expansion capacity and purity of AT-MSCs purified by both procedures immediately
      after isolation and upon consecutive passages. We also investigated possible
      purification-dependent differences in their expression of immune-inhibitory
      factors and cell adhesion molecules. RESULTS: We found that RBC lysis buffer
      treatment is a more robust and easier method to purify AT-MSCs than density
      gradient fractionation. However, the resulting AT-MSC-RBC population contains a
      significantly higher number of CD34(+) cells, particularly during the first
      passages after plating. From passage 4 onward, no significant differences could
      be observed between both populations with respect to the immunophenotype,
      expansion capacity and expression of immune inhibitory factors and cell adhesion
      molecules. CONCLUSIONS: Our data show that RBC lysis buffer treatment may be a
      good alternative to density fractionation, providing a faster, more robust and
      easier method to purify AT-MSCs with biologically preserved characteristics.

PMID- 25065637
TI  - Survival and engraftment of dopaminergic neurons manufactured by a Good
      Manufacturing Practice-compatible process.
AB  - BACKGROUND AIMS: We have previously reported a Good Manufacturing Practice (GMP)
      compatible process for generating authentic dopaminergic neurons in defined media
      from human pluripotent stem cells and determined the time point at which
      dopaminergic precursors/neurons (day 14 after neuronal stem cell [NSC] stage) can
      be frozen, shipped and thawed without compromising their viability and ability to
      mature in vitro. One important issue we wished to address is whether dopaminergic
      precursors/neurons manufactured by our GMP-compatible process can be
      cryopreserved and engrafted in animal Parkinson disease (PD) models. METHODS: In
      this study, we evaluated the efficacy of freshly prepared and cryopreserved
      dopaminergic neurons in the 6-hydroxydopamine-lesioned rat PD model. RESULTS: We
      showed functional recovery up to 6 months post-transplantation in rats
      transplanted with our cells, whether freshly prepared or cryopreserved. In
      contrast, no motor improvement was observed in two control groups receiving
      either medium or cells at a slightly earlier stage (day 10 after NSC stage).
      Histologic analysis at the end point of the study (6 months post-transplantation)
      showed robust long-term survival of donor-derived tyrosine hydroxylase (TH)(+)
      dopaminergic neurons in rats transplanted with day 14 dopaminergic neurons.
      Moreover, TH(+) fibers emanated from the graft core into the surrounding host
      striatum. Consistent with the behavioral analysis, no or few TH(+) neurons were
      detected in animals receiving day 10 cells, although human cells were present in
      the graft. Importantly, no tumors were detected in any grafted rats, but long
      term tumorigenic studies will need to determine the safety of our products.
      CONCLUSIONS: Dopaminergic neurons manufactured by a GMP-compatible process from
      human ESC survived and engrafted efficiently in the 6-OHDA PD rat model.

PMID- 25065638
TI  - Do genetic risk scores for body mass index predict risk of phobic anxiety?
      Evidence for a shared genetic risk factor.
AB  - BACKGROUND: Obesity and anxiety are often linked but the direction of effects is
      not clear. METHOD: Using genetic instrumental variable (IV) analyses in 5911
      female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697
      male participants from the Health Professional Follow-up Study (HPFS, initiated
      1986), we aimed to determine whether obesity increases symptoms of phobic
      anxiety. As instrumental variables we used the fat mass and obesity-associated
      (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score
      (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly
      predict body mass index (BMI). 'Functional' GRSs corresponding with specific
      biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary)
      were considered. The main outcome was phobic anxiety measured by the Crown Crisp
      Index (CCI) in 2004 in the NHS and in 2000 in the HPFS. RESULTS: In observational
      analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms
      [women: beta = 0.05, 95% confidence interval (CI) 0.030-0.068; men: beta = 0.04,
      95% CI 0.016-0.071). IV analyses showed that BMI was associated with higher
      phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in
      the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous,
      non-significant effects of BMI on phobic anxiety symptoms. CONCLUSIONS: Our
      findings do not provide conclusive evidence in favor of the hypothesis that
      higher BMI leads to higher levels of phobic anxiety, but rather suggest that
      genes that influence obesity, in particular FTO, may have direct effects on
      phobic anxiety, and hence that obesity and phobic anxiety may share common
      genetic determinants.

PMID- 25065639
TI  - Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions
      based on combined stains and morphometry techniques.
AB  - BACKGROUND: Prevention and early diagnosis have the greatest potential for public
      health and are the most effective method in the long-term to control oral cancer.
      The aim was to apply PAP staining together with AgNOR staining and morphometric
      analysis in oral exfoliative cytology, to determine the sensitivity and
      specificity of these methods in the detection of malignant changes for the
      purposes of both initial population monitoring and follow-up. METHODS: AgNOR,
      Papanicolau, and morphometric tests were conducted in samples of patients with
      oral cancer, oral potentially malignant disorders and controls (opposite side of
      lesions). Specificity and sensitivity values for each stain method and the curve
      under ROC area were estimated. RESULTS: The diagnostic variables which allowed
      greatest accuracy in identifying malignancy relative to the healthy control were
      cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to
      be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and
      satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio.
      CONCLUSIONS: The total number of AgNOR is a reliable marker for detecting
      neoplastic cells; this method increases sensitivity and specificity by decreasing
      the likelihood of false negatives or positives, as the accuracy obtained was 90%.
      It is also a low-cost, non-invasive, simple methodology that can be recommended
      to help the early detection of oral cancer and monitoring of patients with a
      first diagnosis of cancer.

PMID- 25065640
TI  - Effects of invasive plants on arthropods.
AB  - Non-native plants have invaded nearly all ecosystems and represent a major
      component of global ecological change. Plant invasions frequently change the
      composition and structure of vegetation communities, which can alter animal
      communities and ecosystem processes. We reviewed 87 articles published in the
      peer-reviewed literature to evaluate responses of arthropod communities and
      functional groups to non-native invasive plants. Total abundance of arthropods
      decreased in 62% of studies and increased in 15%. Taxonomic richness decreased in
      48% of studies and increased in 13%. Herbivorous arthropods decreased in response
      to plant invasions in 48% of studies and increased in 17%, likely due to direct
      effects of decreased plant diversity. Predaceous arthropods decreased in response
      to invasive plants in 44% of studies, which may reflect indirect effects due to
      reductions in prey. Twenty-two percent of studies documented increases in
      predators, which may reflect changes in vegetation structure that improved
      mobility, survival, or web-building for these species. Detritivores increased in
      67% of studies, likely in response to increased litter and decaying vegetation;
      no studies documented decreased abundance in this functional group. Although many
      researchers have examined effects of plant invasions on arthropods, sizeable
      information gaps remain, specifically regarding how invasive plants influence
      habitat and dietary requirements. Beyond this, the ability to predict changes in
      arthropod populations and communities associated with plant invasions could be
      improved by adopting a more functional and mechanistic approach. Understanding
      responses of arthropods to invasive plants will critically inform conservation of
      virtually all biodiversity and ecological processes because so many organisms
      depend on arthropods as prey or for their functional roles, including
      pollination, seed dispersal, and decomposition. Given their short generation
      times and ability to respond rapidly to ecological change, arthropods may be
      ideal targets for restoration and conservation activities.

PMID- 25065642
TI  - Efficacy of rehabilitation programs for improving muscle strength in people with
      hip or knee osteoarthritis: a systematic review with meta-analysis.
AB  - To analyse the effect of exercise-based rehabilitation programs for improving
      lower limb muscle strength in individuals with hip or knee osteoarthritis (OA). A
      systematic search utilizing seven databases identified randomized controlled
      trials (RCTs) evaluating lower limb strength outcomes of exercise-based
      interventions for participants with hip or knee OA. All studies were screened for
      eligibility and methodological quality. Quality of evidence was assessed using
      Grading of Recommendation, Assessment, Development and Evaluation (GRADE)
      approach. Data were pooled and meta-analyses performed where appropriate. Forty
      RCTs were included and the majority (77%) involved resistance based exercise
      programs. For knee OA populations, there was high quality evidence for improved
      knee extension (standardized mean difference (SMD) = 0.47, 95% confidence
      intervals (CI) 0.29, 0.66) and flexion strength (SMD = 0.74, 95% CI 0.56, 0.92)
      with low-intensity resistance program when compared to a control at short term
      (ST) follow-up. There was moderate quality evidence for a large effect favouring
      high-intensity resistance programs (SMD = 0.76, 95% CI 0.47, 1.06) when compared
      to a control. This effect was sustained at intermediate term (IT) follow-up (SMD
      = 0.80, 95% CI 0.44, 1.17). Few studies reported on outcomes at long term (LT)
      follow-up. Only one study reported on a population with hip OA. When compared to
      a control group, high-intensity resistance exercise demonstrated moderate quality
      of evidence for large and sustained improvements for knee muscle strength in knee
      OA patients. Further work is needed to compare different modes of exercise at a
      LT follow-up for knee OA patients and to address the dearth of literature
      evaluating exercise interventions in people with hip OA. 

PMID- 25065641
TI  - Low back pain beliefs are associated to age, location of work, education and pain
      related disability in Chinese healthcare professionals working in China: a cross
      sectional survey.
AB  - BACKGROUND: Low back pain (LBP) is the leading cause of disability worldwide.
      Evidence pointing towards a more efficacious model of care using a
      biopsychosocial approach for LBP management highlights the need to understand the
      pain-related beliefs of patients and those who treat them. The beliefs held by
      healthcare professionals (HCPs) are known to influence the treatment advice given
      to patients and consequently management outcomes. Back pain beliefs are known to
      be influenced by factors such as culture, education, health literacy, place of
      work, personal experience of LBP and the sequelae of LBP such as disability.
      There is currently a knowledge gap among these relationships in non-western
      countries. The aim of this study was to examine the associations between LBP
      related beliefs among Chinese HCPs and characteristics of these HCPs. METHODS: A
      convenience sample of 432 HCPs working in various health settings in Shanghai,
      China, completed a series of questionnaires assessing their demographic
      characteristics, LBP status, pain-related disability and their beliefs about
      their own LBP experience, using the Back beliefs Questionnaire (BBQ) and the Fear
      Avoidance Beliefs Questionnaire (FABQ). RESULTS: Younger Chinese HCPs (20-29
      years) held more negative beliefs and attitudes related to LBP compared to older
      HCPs (>40years; BBQ mean difference [95% CI]: 2.4 [0.9 - 3.9], p = 0.001). HCPs
      working outside tertiary hospitals had poorer beliefs concerning the inevitable
      consequences of LBP (BBQ mean difference [95% CI]: -2.4 [-3.8 - -1.0], p =
      0.001). HCPs who experienced LBP had higher level of fear avoidance beliefs when
      experiencing high LBP-related disability (FABQ-physical mean difference [95% CI]:
      2.8 [1.5 - 4.1], p < 0.001; FABQ-work mean difference [95% CI]: 6.2 [4.0 - 8.4],
      p < 0.001)) and had lower level of fear avoidance beliefs if they had completed
      postgraduate study (FABQ-physical mean difference [95% CI]: 2.9 [-5.8 - 0.0], p =
      0.049). CONCLUSION: This study suggests that LBP-related beliefs and attitudes
      among Chinese HCPs are influenced by age, location of work, level of LBP-related
      disability and education level. Understanding back pain beliefs of Chinese HCPs
      forms an important foundation for future studies into the condition and its
      management in China.

PMID- 25065643
TI  - Atypical variants of right ventricular outflow arrhythmias.
AB  - BACKGROUND: Right ventricular outflow tract (RVOT) arrhythmias are a common form
      of ventricular tachycardia (VT) in patients with structurally normal heart. The
      underlying mechanism is due to triggered activity. Mapping and ablation is
      relatively straightforward targeting the earliest point of activation. Previously
      reported causes of difficult ablation in the RVOT region include under recognized
      right ventricular cardiomyopathy/sarcoidosis, presence of endocavitary
      structures, close proximity to the coronary vasculature, and origin from non-RVOT
      structures. METHODS AND RESULTS: We identified all patients undergoing
      PVCs/sustained RVOT VT ablation from January 2013 to December 2013. This included
      33 patients. Of these, we identified procedures that were considered difficult
      despite a single morphology arrhythmia being targeted and no underlying
      cardiomyopathy present. Difficulty was specifically considered when ablation at
      the earliest site of activation was not successful and eventual successful
      ablation was at a distance of greater than 15 mm from the early activation site.
      We identified 3 patients (n = 3, 100% male) with evidence of reentrant arrhythmia
      based on slow conduction zones necessary for the tachycardia/arrhythmia, mid
      diastolic signals during VT or preceding bigeminal PVCs, pace mapping from the
      site abnormal signals reproducing the arrhythmia morphology but with prominent
      conduction delay, the entire cycle length of the tachycardia or coupling interval
      for the PVCs being mapping, or based on reset characteristics. CONCLUSION: In
      patients with atypical forms of RVOT VT, careful mapping and ablation of the
      myocardial sleeves near the pulmonic valve can eliminate the arrhythmia.

PMID- 25065644
TI  - Exosome-mediated extracellular release of polyadenylate-binding protein 1 in
      human metastatic duodenal cancer cells.
AB  - Exosomes are small vesicles secreted from cells that transport their embedded
      molecules through bidirectional exocytosis- and endocytosis-like pathways.
      Expression patterns of exosomal molecules such as proteins and RNAs can be
      indicative of cell type since their signature is thought to be unique among
      cells. Using human primary (AZ-521) and metastatic (AZ-P7a) duodenal cancer cell
      lines, we conducted a comparative exosomal proteome analysis to identify proteins
      with metastatic marker potential. As determined by LC-MS/MS and Western blot
      analyses, polyadenylate-binding protein 1 (PABP1) was found to be predominantly
      abundant in AZ-P7a exosomes. The amount of exosomal PABP1 in AZ-P7a cells
      increased by treating the cells with inhibitors for the classical ER/Golgi
      secretory pathway (brefeldin A and monensin) and the ubiquitin-proteasome pathway
      (MG-132 and PYR-41). Treatment of AZ-P7a cells with the neutral sphingomyelinase
      inhibitor GW4869, which suppresses exosome release, not only reduced the amount
      of exosomal PABP1 but also produced PABP1-immunoreactive products cleaved via a
      proteolysis-like process. Taken together, these results suggest that AZ-P7a cells
      do not tolerate intracellular PABP1 accumulation and are thus exported into the
      extracellular milieu by the exosome-mediated pathway. In addition, PABP1 has a
      potential use as a biomarker for metastatic duodenal cancer. 

PMID- 25065645
TI  - The genome-scale metabolic network of Ectocarpus siliculosus (EctoGEM): a
      resource to study brown algal physiology and beyond.
AB  - Brown algae (stramenopiles) are key players in intertidal ecosystems, and
      represent a source of biomass with several industrial applications. Ectocarpus
      siliculosus is a model to study the biology of these organisms. Its genome has
      been sequenced and a number of post-genomic tools have been implemented. Based on
      this knowledge, we report the reconstruction and analysis of a genome-scale
      metabolic network for E. siliculosus, EctoGEM (http://ectogem.irisa.fr). This
      atlas of metabolic pathways consists of 1866 reactions and 2020 metabolites, and
      its construction was performed by means of an integrative computational approach
      for identifying metabolic pathways, gap filling and manual refinement. The
      capability of the network to produce biomass was validated by flux balance
      analysis. EctoGEM enabled the reannotation of 56 genes within the E. siliculosus
      genome, and shed light on the evolution of metabolic processes. For example, E.
      siliculosus has the potential to produce phenylalanine and tyrosine from
      prephenate and arogenate, but does not possess a phenylalanine hydroxylase, as is
      found in other stramenopiles. It also possesses the complete eukaryote molybdenum
      co-factor biosynthesis pathway, as well as a second molybdopterin synthase that
      was most likely acquired via horizontal gene transfer from cyanobacteria by a
      common ancestor of stramenopiles. EctoGEM represents an evolving community
      resource to gain deeper understanding of the biology of brown algae and the
      diversification of physiological processes. The integrative computational method
      applied for its reconstruction will be valuable to set up similar approaches for
      other organisms distant from biological benchmark models. 

PMID- 25065646
TI  - Proteomic characterization of human coronary thrombus in patients with ST-segment
      elevation acute myocardial infarction.
AB  - Acute myocardial infarction with ST-segment elevation (STEMI) initiates with
      intraluminal thrombosis and results in total occlusion of the coronary artery. To
      date, characterization of the coronary thrombus proteome in STEMI patients has
      not been yet accomplished. Therefore, we aimed to perform an in-depth proteomic
      characterization of the human coronary thrombus by means of three different
      approaches: 2-DE followed by mass spectrometry (MALDI MS/MS), 1-DE combined
      either with liquid chromatography coupled to mass spectrometry in a MALDI TOF/TOF
      (LC-MALDI-MS/MS), or in a LTQ-Orbitrap (LC-ESI-MS/MS). This approach allowed us
      to identify a total of 708 proteins in the thrombus. Expression in coronary
      thrombi (n=20) of 14 proteins was verified, and the expression of fibrin and 6
      cell markers (platelets, monocytes, neutrophils, eosinophils, T-cells and B
      cells) quantified by selected reaction monitoring (SRM). A positive correlation
      of 5 proteins (fermitin homolog 3, thrombospondin-1, myosin-9, beta parvin and
      ras-related protein Rap-1b) with CD41 was found, pointing out the potential
      activation of a focal adhesion pathway within thrombus platelets. DIDO1 protein
      was found to correlate negatively with thrombus fibrin, and was found up
      regulated in the plasma of these STEMI patients, which may constitute a starting
      point for further analyses in the search for biomarkers of thrombosis. BIOLOGICAL
      SIGNIFICANCE: The proteomic characterization of the human coronary thrombus may
      contribute to a better understanding of the mechanisms involved in acute coronary
      syndrome, and thus pave the road for the identification of new therapeutic
      targets that may help addressing this and other thrombotic diseases. A novel
      methodology to characterize thrombus composition and expression of a sub-group of
      proteins is hereby described, which allowed linking protein expression with
      cellular and ECM matrix composition of the thrombus. Five proteins (fermitin
      homolog 3, thrombospondin-1, myosin-9, beta parvin and ras-related protein Rap
      1b) co-express within the human coronary thrombus with CD41, pointing out the
      potential activation of a focal adhesion pathway within thrombus platelets during
      thrombus formation. Besides, the protein death-inducer obliterator 1, found to be
      expressed within the human coronary thrombus, has been proved to increase in the
      plasma of STEMI patients, which constitutes an important starting point for
      further analyses in the search for biomarkers of thrombosis.

PMID- 25065647
TI  - Interacting proteins of protein kinase A regulatory subunit in Saccharomyces
      cerevisiae.
AB  - cAMP-dependent protein kinase mediates many extracellular signals in eukaryotes.
      The compartmentalization of PKA is an important level of control of the
      specificity of signal transduction mediated by cAMP. Unlike mammalian PKA for
      which proof insights in the mechanism that controls its localization through
      anchoring proteins (AKAPs) has been obtained, in the case of Saccharomyces
      cerevisiae PKA there was little information available. In this work, we present
      results that demonstrate the isolation and identification of yeast PKA regulatory
      subunit (Bcy1) associated proteins using a MS-based proteomic analysis and a
      bioinformatic approach. The verification of some of these interactions was
      assessed by immunoprecipitation, pull down and co-localization by subcellular
      fractionation. The key role of positively charged residues present in the
      interaction domain of the identified proteins was demonstrated. The defined
      interaction domain has therefore different molecular characteristics than
      conventional AKAP domains. Finally we assess initial experiments to visualize the
      physiological relevance of the interaction of both Ira2 and Hsp60 with Bcy1. Bcy1
      interacts with Ira2 tethering PKA to the Ras complex and Hsp60 chaperone
      localizes PKA to mitochondria and has a role in the kinase stability. BIOLOGICAL
      SIGNIFICANCE: Our work has an important impact in the field of signal
      transduction especially of protein kinase A. Components of the cAMP signaling
      cascade are localized in the cell via scaffold proteins named AKAPs that
      contribute to the high level specific regulation of the cAMP-PKA-signaling
      pathway. In the unicellular eukaryote Saccharomyces cerevisiae PKA has a
      pleiotropic role in the cell and the compartmentalization therefore is key to
      achieve the specificity in the response. At present all AKAPs have been described
      in mammals and it is unknown whether functional homologs of mammalian AKAPs exist
      in yeast. Therefore, it is unknown which molecular features of the mammalian
      anchoring proteins are general and which are distinctive. We have identified and
      characterized interacting proteins of protein kinase A regulatory subunit in
      Saccharomyces cerevisiae, through a proteomic and bioinformatic approach. Bcy1
      tethering proteins have a domain in which charged positives residues are key for
      the interaction with regulatory subunit of PKA and Bcy1 N-terminus is important
      in the interaction. In mammalian AKAPs a hydrophobic amino acid face of an
      amphipathic alpha-helix is essential for the high affinity of the binding
      interaction. The results obtained in this work seem to indicate that the domains
      identified in the interacting Bcy1 proteins have a structural nature of the
      interaction different than those defined for mammalian AKAPs-R interaction. Not
      only positive charged residues are involved as distinctive molecular determinants
      but also the hydrophobic face of the helix in which they are included was not
      relevant in the interaction with Bcy1. Even though generally the use of very well
      characterized models is essential to answer questions, as would be in this case
      AKAPs from mammals, the study of other alternative models contributes to the
      building of more universal concepts.

PMID- 25065648
TI  - Phosphoproteome analysis reveals new drought response and defense mechanisms of
      seedling leaves in bread wheat (Triticum aestivum L.).
AB  - Drought is a major form of abiotic stress that significantly affects plant growth
      and development. In this study, we performed the first phosphoproteome analysis
      of seedling leaves from two bread wheat cultivars (Hanxuan 10 and Ningchun 47)
      subjected to drought stress. As a result, a total of 191 and 251 unique
      phosphopeptides, representing 173 and 227 phosphoproteins in two cultivars,
      respectively, were identified as being significant changes in phosphorylation
      level (SCPL) under drought stress. Through the comparison of SCPL phosphoproteins
      between two cultivars, 31 common SCPL phosphoproteins were found in both
      cultivars. Function analysis showed that the SCPL phosphoproteins in the two
      cultivars are mainly involved in three biological processes: RNA
      transcription/processing, stress/detoxification/defense, and signal transduction.
      Further analyses revealed that some SCPL phosphoproteins may play key roles in
      signal transduction and the signaling cascade under drought stress. Furthermore,
      some phosphoproteins related to drought tolerance and osmotic regulation
      exhibited significant phosphorylation changes. This study used a series of
      bioinformatics tools to profile the phosphorylation status of wheat seedling
      leaves under drought stress with greater accuracy. BIOLOGICAL SIGNIFICANCE:
      Drought is of the most studied abiotic stresses, because it severely restricts
      the development and yield of plants. In this study, large numbers of stress
      related phosphoproteins are identified from the two bread wheat cultivars. These
      phosphoproteins contribute to signal transduction, osmotic regulation and ROS
      scavenging under water stress. This work provides a detailed insight into the
      mechanisms of drought response and defense in bread wheat from the perspective of
      phosphoproteomics, and identifies some important drought-tolerant candidates for
      further transgenosis study and incorporation into the breeding of resistant
      cultivars.

PMID- 25065649
TI  - Injectable self-gelling composites for bone tissue engineering based on gellan
      gum hydrogel enriched with different bioglasses.
AB  - Hydrogels of biocompatible calcium-crosslinkable polysaccharide gellan gum (GG)
      were enriched with bioglass particles to enhance (i) mineralization with calcium
      phosphate (CaP); (ii) antibacterial properties and (iii) growth of bone-forming
      cells for future bone regeneration applications. Three bioglasses were compared,
      namely one calcium-rich and one calcium-poor preparation both produced by a sol
      gel technique (hereafter referred to as A2 and S2, respectively) and one
      preparation of composition close to that of the commonly used 45S5 type
      (hereafter referred to as NBG). Incubation in SBF for 7 d, 14 d and 21 d caused
      apatite formation in bioglass-containing but not in bioglass-free samples, as
      confirmed by FTIR, XRD, SEM, ICP-OES, and measurements of dry mass, i.e. mass
      attributable to polymer and mineral and not water. Mechanical testing revealed an
      increase in compressive modulus in samples containing S2 and NBG but not A2.
      Antibacterial testing using biofilm-forming meticillin-resistant staphylococcus
      aureus (MRSA) showed markedly higher antibacterial activity of samples containing
      A2 and S2 than samples containing NBG and bioglass-free samples. Cell biological
      characterization using rat mesenchymal stem cells (rMSCs) revealed a stimulatory
      effect of NBG on rMSC differentiation. The addition of bioglass thus promotes GG
      mineralizability and, depending on bioglass type, antibacterial properties and
      rMSC differentiation.

PMID- 25065650
TI  - Contact allergy to biguanides might explain cases of unresolved eyelid
      dermatitis.

PMID- 25065651
TI  - Supercharging of delayed pedicled transverse rectus abdominis myocutaneous flaps,
      is it a viable option?
AB  - INTRODUCTION: Arterial and venous insufficiency may become evident even in
      delayed pedicled TRAM flaps. This study assesses the possibility of using the
      previously ligated deep inferior epigastric vessels for microvascular
      supercharging during reconstruction. METHODS: Twenty-two patients underwent delay
      by ligation of the inferior epigastric vessels prior to TRAM flap breast
      reconstruction. The deep inferior epigastric vessels were excised at the time of
      reconstruction 10-14 days after delay and microscopically examined for vascular
      compromise that might prevent use in microvascular anastomosis at the time of
      reconstruction. RESULTS: 20/22 (91%) of the deep inferior epigastric vessels (20
      arteries and accompanying veins) showed clot immediately adjacent to the ligature
      only and 2/22 (9%) showed clot extending only 5-10 mm. None of these vessels (0%)
      showed clot in the distal 2 cm of their length (adjacent to the flap). Evidence
      of intramural hematoma, delamination, and endothelial abnormalities were not
      found in any of the vessels. An additional patient who was a 48-year-old female
      underwent bilateral pedicled TRAM flap breast reconstruction and one of the flaps
      exhibited inadequate capillary refill intraoperatively after transfer to the
      mastectomy defect. Supercharging of the flap utilizing the previously ligated
      inferior epigastric artery improved capillary refill and the flap survived
      completely postoperatively. CONCLUSION: Our findings demonstrate patency of the
      inferior epigastric vessels after ligation for TRAM delay during the time frame
      usually used for delay to take effect.

PMID- 25065652
TI  - Hyponatremia as a fall predictor in a geriatric trauma population.
AB  - INTRODUCTION: Approximately one in three older adults fall each year, resulting
      in a significant proportion of geriatric traumatic injuries. In a hospital with a
      focus on geriatric fall prevention, we sought to characterize this population to
      develop targeted interventions. As mild hyponatremia, defined as a serum sodium
      <135meq/L, has been reported to be associated with falls, unsteadiness and
      attention deficits, we hypothesized that hyponatremia is associated with falls in
      our geriatric trauma population. METHODS: Gender, age, pre-existing conditions
      (cardiac disease, diabetes, hematologic disorder, liver disease, malignancy,
      musculoskeletal disorder, neurological disorder, obesity, psychiatric disorder,
      pulmonary disease, renal disease, thyroid disease), mechanism of injury and
      admitting serum sodium level were queried for all geriatric trauma admissions
      from 2008 to 2011. Mechanism of injury was coded as falls admissions and non
      falls admissions. Admitting serum sodium levels were coded as hyponatremic
      (<135mmol/L) and not hyponatremic (>=135mmol/L). RESULTS: Of the 2370 geriatric
      trauma admissions during the study period, there were 1841 (77.7%) falls
      admissions and 293 (12.4%) patients who were hyponatremic. Gender, age,
      neurological disorder, hematologic disorder, and hyponatremia were found to be
      significant predictors of falls in both univariate and multivariable analyses.
      CONCLUSION: Hyponatremic patients are significantly more likely to be admitted
      for a fall than non-hyponatremic patients, when adjusting for age, neurological
      disorder, and hematologic disorder. Consequently, hyponatremia identification and
      management should be an integral part of any geriatric trauma fall prevention
      programme. Additionally, if hyponatremia is found during a geriatric fall workup,
      it should be corrected prior to discharge and closely monitored by a primary care
      physician to prevent recurrent episodes of falls.

PMID- 25065653
TI  - Stepped care treatment delivery for depression: a systematic review and meta
      analysis.
AB  - BACKGROUND: In stepped care models patients typically start with a low-intensity
      evidence-based treatment. Progress is monitored systematically and those patients
      who do not respond adequately step up to a subsequent treatment of higher
      intensity. Despite the fact that many guidelines have endorsed this stepped care
      principle it is not clear if stepped care really delivers similar or better
      patient outcomes against lower costs compared with other systems. We performed a
      systematic review and meta-analysis of all randomized trials on stepped care for
      depression. METHOD: We carried out a comprehensive literature search. Selection
      of studies, evaluation of study quality and extraction of data were performed
      independently by two authors. RESULTS: A total of 14 studies were included and 10
      were used in the meta-analyses (4580 patients). All studies used screening to
      identify possible patients and care as usual as a comparator. Study quality was
      relatively high. Stepped care had a moderate effect on depression (pooled 6-month
      between-group effect size Cohen's d was 0.34; 95% confidence interval 0.20-0.48).
      The stepped care interventions varied greatly in number and duration of treatment
      steps, treatments offered, professionals involved, and criteria to step up.
      CONCLUSIONS: There is currently only limited evidence to suggest that stepped
      care should be the dominant model of treatment organization. Evidence on (cost-)
      effectiveness compared with high-intensity psychological therapy alone, as well
      as with matched care, is required.

PMID- 25065654
TI  - An aggressive presentation of colorectal cancer with an atypical
      lymphoproliferative pattern of metastatic disease: a case report and review of
      the literature.

PMID- 25065655
TI  - Metastatic colorectal cancer treatment patterns according to kirsten rat sarcoma
      viral oncogene homolog genotype in U.S. Community-based oncology practices.
AB  - INTRODUCTION: In 2008, the National Comprehensive Cancer Network guidelines were
      revised in light of the identification of the Kirsten Rat Sarcoma Viral Oncogene
      Homolog (KRAS) gene as a biomarker of nonresponse to epidermal growth factor
      receptor inhibitors. This study sought to describe and compare real-world
      treatment patterns of metastatic colorectal cancer (mCRC) according to KRAS
      genotype in community-based oncology practices in the United States. MATERIALS
      AND METHODS: Data from the ACORN (ACORN LLC, Memphis, TN) electronic medical
      record data warehouse, containing data of approximately 180,000 patients from 12
      oncology practices across the United States were used. Records of adult patients
      with mCRC who had undergone KRAS testing between January 2008 and December 2011
      were evaluated. Patient demographic characteristics, KRAS genotype, and treatment
      patterns were identified and compared. RESULTS: Six hundred forty-eight mCRC
      patients who were tested for KRAS were identified. Of these, 48.1% had wild type
      (WT), 42.3% mutant, and 9.6% unknown genotypes. Most patients (72.1%) were tested
      in 2009 or later, after the guideline revision. Bevacizumab-containing
      combinations were the most common first-line regimens in KRAS mutant and WT
      patients. Approximately 90% of patients received at least 1 line of therapy,
      however, WT patients received significantly more lines of therapy than KRAS
      mutant patients (2.6 +/- 1.5 vs. 2.1 +/- 1.2; P < .001). CONCLUSIONS: KRAS WT and
      mutant genotypes had similar first-line regimens; however, WT patients received
      more lines of therapy. Although there does not appear to be a lag between changes
      in guidelines and treatment practice, professional and government organizations
      must keep up with the changing science and disseminate this information to
      oncologists in a timely manner.

PMID- 25065657
TI  - Chemically modified gold superatoms and superatomic molecules.
AB  - Clusters of gold atoms can be viewed as superatoms, in which valence electrons
      confined in the particles occupy atomic-like, discrete electronic levels.
      Chemical modification of the gold superatoms and their aggregated molecules
      (superatomic molecules) with organic ligands is a promising approach for their
      application as the building units of new functional materials. This account
      surveys the present status of the rapidly growing field of gold superatoms and
      superatomic molecules protected by thiolates and phosphines. The major aim of
      this article is to provide a simple picture for the structure, stability and
      bonding scheme of chemically modified superatoms and superatomic molecules for
      the development of a new class of hierarchical materials. 

PMID- 25065656
TI  - A novel approach for detecting viable and tissue-specific circulating tumor cells
      through an adenovirus-based reporter vector.
AB  - BACKGROUND: Circulating tumor cells (CTCs) hold great promise as biomarkers and
      are a direct source of tumor cells through a simple blood draw. However, CTCs are
      rare and their detection requires sensitive and specific methods to overcome the
      overwhelming hematocyte population. Therefore, CTC detection remains technically
      challenging. METHODS: An assay was developed for detecting viable and tissue
      specific CTCs using a tropism-enhanced and conditionally replicating reporter
      adenovirus (CTC-RV). Adenoviral replication was made prostate-specific by placing
      the E1A gene under the control of the probasin promoter and prostate-specific
      antigen enhancer (PSE-PBN). Viral tropism was expanded through capsid-displayed
      integrin targeting peptides. A secreted reporter, humanized Metridia Luciferase
      (hMLuc), was engineered for expression during the major late phase of viral
      replication. The assay involves red blood cell lysis, cell collection, viral
      infection, and subsequent quantification of reporter activity from cellular
      media. Assay and reporter stability, cell specificity and sensitivity were
      evaluated in cell dilution models in human blood. RESULTS: A conditionally
      replicating prostate-selective adenovirus reporter and CTC assay system were
      generated. The secreted reporter, MLuc, was found to be stable for at least 3
      days under assay conditions. CTC detection, modeled by cell dilution in blood,
      was selective for androgen receptor positive prostate cancer (PCa) cells. Serial
      dilution demonstrated assay linearity and sensitivity to as few as three cells.
      Prostate cancer cell viability declined after several hours in anticoagulated
      blood at ambient temperatures. CONCLUSIONS: Conditionally replicative adenoviral
      vectors and secreted reporters offer a functional method to detect viable CTCs
      with cell specificity and high sensitivity.

PMID- 25065658
TI  - [Sexual health management in oncology].
AB  - The cancer and its treatments have consequences on the intimacy and the sexuality
      of the patients and their partners. Supporting them with valid information, by
      spotting risk factors, warning complications, and by bringing answers to the
      often commonplace concerns of the patients, is an ethical duty. This intervention
      concerning the sexual health is collectively realized by all the healthcare
      professionals, in an organization of gradual answer, and benefits ideally from
      the clinical and educational expertise of sex therapists associated to the
      supporting care offer. 

PMID- 25065659
TI  - [A case of yellow urticaria].

PMID- 25065660
TI  - [Inadequate involvement of general practitioners in end-of-life's decisions in an
      intensive care unit].
AB  - INTERESTS AND OBJECTIVES: Patients' general practitioners (GPs) could be relevant
      consultants for collegial decisions of withholding or withdrawing treatment (WWT)
      defined by the Leonetti law. We therefore studied their implication by
      intensivists in end-of-life decisions and collected their feelings. Their wishes
      for the coming law revision were also investigated. METHODS: Retrospective
      descriptive study conducted in the polyvalent intensive care unit (ICU) of
      Longjumeau's hospital (France) using a distributed questionnaire to GPs of
      patients who benefited from collegial decisions of WWT in 2012. RESULTS: The
      response rate was 60.4% (32/53) and only 18.8% of the respondents participated as
      a consultant in WWT's decision for their patient. Two GPs out of three reported
      that they never participate in such decisions for their others patients. All
      uninvolved GPs did not contribute because intensivists did not consult them. Only
      43.7% of GPs were contacted by intensivists during the stay and 21.9% at the
      discharge or death of their patient. GPs took news about their patient during ICU
      hospitalization in 37.5% of cases. Regarding uninvolved GPs, their participation
      could have changed WWT's decisions made for two patients (7.7%). Most respondents
      felt available (78.1%) and skilled (81.2 %) to participate in this kind of
      decision. A third was also questioned by the patient's family about it. Only
      21.7% of GPs report to be familiar with the French end-of-life legislation. In
      case of a next revision, two thirds considered important to make the use of GPs
      obligatory in such decisions. CONCLUSION: Despite an undeniable interest, GPs are
      rarely involved in collegial processes of WWT in ICUs, partially related to an
      insufficient knowledge of the law by the healthcare providers. At the dawn of end
      of-life law's revision, their share could however improve our practices in this
      field.

PMID- 25065661
TI  - [Fatal strongyloidiasis following corticosteroid therapy].

PMID- 25065662
TI  - [Letter on the article: "Breast cancer screening". From conclusions.... to
      acts!].

PMID- 25065663
TI  - Acute interstitial pneumonia following heroin inhalation.

PMID- 25065664
TI  - [Biotherapies in metastatic colorectal cancers in 2014].
AB  - The treatment of metastatic colorectal cancer has been transformed during the
      last decade with biotherapies, two of them were marketed in 2013. Four agents are
      monoclonal antibodies, while the fifth agent is a tyrosine kinase inhibitor. Two
      agents are inhibitors of the EGF-receptor pathway, cetuximab and panitumumab, and
      have as class-toxicity, cutaneous toxicity. The other three agents are
      bevacizumab, aflibercept and regorafenib, and interact with angiogenesis, they
      are associated with a risk of vascular toxicity, mainly hypertension. These
      agents participate to an improvement of disease control at the metastatic stage,
      and in some cases, favour the curative surgical resection of metastases. Their
      use is discussed in multidisciplinary meetings dedicated to gastrointestinal
      cancers, in the presence of liver surgeons. 

PMID- 25065665
TI  - Sinonasal eosinophilic angiocentric fibrosis: a systematic review.
AB  - BACKGROUND: Eosinophilic angiocentric fibrosis (EAF) is a benign rare lesion of
      the upper respiratory mucosa. EAF most commonly presents with an obstructive
      nasal mass. Due to the rarity of EAF, case reports and case studies have
      predominated the literature. This systematic review discusses the demographics,
      clinical presentation, associated findings, management, and outcomes of this
      uncommon entity. METHODS: The PubMed database was searched for all articles
      describing patients diagnosed with sinonasal EAF. Additional cases were examined
      from the bibliographies of selected articles. Demographics, clinical
      presentation, associated findings, radiography, management, and outcome were
      analyzed. RESULTS: Fifty-two cases were included from 34 articles, including 1
      case from our institution. The most common presenting symptom was nasal
      obstruction (78.8%). Fourteen patients (26.9%) had a previous history of nasal
      surgery or trauma. Surgical resection alone was the most commonly used primary
      treatment approach (50.0%), resulting in the greatest proportion of disease-free
      patients (55.6%) over a median follow-up period of 36 months. A combination of
      surgery and corticosteroids was the second-most-common treatment modality, used
      in 28.8% of cases. Of the 40 cases reporting patient outcomes, 100% of patients
      were alive at follow-up independent of treatment modality. CONCLUSION: To date,
      this review contains the largest number of patients with sinonasal EAF.
      Aggressive surgical resection alone constitutes the most common treatment
      modality and may be most effective at eradicating disease.

PMID- 25065666
TI  - Nucleotide and amino acid variations of tannase gene from different Aspergillus
      strains.
AB  - Tannase is an enzyme that catalyses the hydrolysis of ester bonds present in
      tannins. Most of the scientific reports about this biocatalysis focus on aspects
      related to tannase production and its recovery; on the other hand, reports
      assessing the molecular aspects of the tannase gene or protein are scarce. In the
      present study, a tannase gene fragment from several Aspergillus strains isolated
      from the Mexican semidesert was sequenced and compared with tannase amino acid
      sequences reported in NCBI database using bioinformatics tools. The genetic
      relationship among the different tannase sequences was also determined. A
      conserved region of 7 amino acids was found with the conserved motif GXSXG common
      to esterases, in which the active-site serine residue is located. In addition, in
      Aspergillus niger strains GH1 and PSH, we found an extra codon in the tannase
      sequences encoding glycine. The tannase gene belonging to semidesert fungal
      strains followed a neutral evolution path with the formation of 10 haplotypes, of
      which A. niger GH1 and PSH haplotypes are the oldest. 

PMID- 25065667
TI  - Modulation of Pb(II) caused aortal constriction by eugenol and carvacrol.
AB  - Exposure to lead is known to cause vasoconstriction, exact mechanism of which
      remains to be elucidated. In this study, we investigate contractile responses of
      rat aortal rings equilibrated with Pb(II) in organ bath system, explore pathways
      responsible for hypercontraction and examine two ameliorators of lead-induced
      hypercontraction. At 1 MUmol L(-1) Pb(II), aortal rings showed an average
      increase of 50% in isometric contraction. Incubation of rings, unexposed to
      Pb(II), with 1 MUmol L(-1) sodium nitroprusside (nitric oxide (NO) donor), 100
      MUmol L(-1) apocynin (reactive oxygen species (ROS) inhibitor), and 100 MUmol L(
      1) indomethacin (cyclooxygenase inhibitor) lead to decrease in phenylephrine
      induced contraction by 31, 27, and 29%, respectively. This decrease of
      contraction for Pb(II)-exposed rings was 48, 53, and 38%, respectively,
      indicating that ROS- and NO-dependent components of contractions are
      significantly elevated in Pb(II)-induced hypercontraction. Cyclooxygenase
      dependent contractile component did not show significant elevation. Eugenol and
      carvacrol are plant-derived phenols known to possess antioxidant activity and
      hence could act as possible ameliorators of hypercontraction. At saturating
      concentrations of 100 MUmol L(-1), eugenol and carvacrol caused a decrease in
      contraction by 38 and 42% in unexposed rings and 46 and 50% in Pb(II)-exposed
      rings. Co-incubation of rings with eugenol/carvacrol and various inhibitors
      suggests that both these active principles exert their relaxant effect via
      quenching of ROS and stimulation of NO synthesis. To conclude, Pb(II) is shown to
      induce hypercontraction of aortal rings through elevation of ROS and depletion of
      NO. This hypercontraction is effectively mitigated by eugenol and carvacrol.

PMID- 25065668
TI  - A phase I pharmacokinetics study of lapatinib and tamoxifen in metastatic breast
      cancer (EORTC 10053 Lapatam study).
AB  - OBJECTIVE: This phase I study assessed the pharmacokinetic (PK), tolerability,
      safety and preliminary clinical activity of tamoxifen (T) and lapatinib (L) in
      patients with metastatic breast cancer (MBC). METHODS: Patients (pts) with
      hormone receptor positive MBC, irrespective of HER-2 status, were randomly
      assigned to T -> T + L group, tamoxifen in cycle 1 for 28 days then adding
      lapatinib on day 1 of cycle 2; or L -> T + L group, lapatinib in cycle 1 for 14
      days, then adding tamoxifen on day 1 of cycle 2 to evaluate the potential drug
      drug PK interaction at steady-state. The dose of tamoxifen was 20 mg/day and
      lapatinib 1500 mg/day. RESULTS: Twenty-five pts were enrolled of which 23 started
      treatment, five (22%) of them were HER-2 positive. Median age was 59 years and
      96% had PS <=1. Eleven (91.7%) pts in the T -> T + L group and 10 (76.9%) in L ->
      T + L group received at least 2 cycles of treatment. The most frequently reported
      drug-related adverse events (>25% of patients) were diarrhoea (62%), anaemia
      (56%), rash (52%), fatigue (52%), dermatology other (34%) and leukopenia (28%).
      Grade 3-4 drug-related toxicities were infrequent (<10%). No cardiotoxicity was
      observed. T plasma concentrations did not appeared to be affected by the presence
      of lapatinib. L steady-state plasma concentrations were 20% lower after 28 days
      of co-administration with T. Eight (36.4%) patients experienced stable disease
      and median progression free survival was 2.7 months. CONCLUSIONS: The combination
      of L and T was safe and clinically active. T affected L plasma concentrations,
      which remained within the therapeutic index.

PMID- 25065670
TI  - Identification of lipid and saccharide constituents of whole microalgal cells by
      13C solid-state NMR.
AB  - Microalgae are unicellular organisms in which plasma membrane is protected by a
      complex cell wall. The chemical nature of this barrier is important not only for
      taxonomic identification, but also for interactions with exogenous molecules such
      as contaminants. In this work, we have studied freshwater (Chlamydomonas
      reinhardtii) and marine (Pavlova lutheri and Nannochloropsis oculata) microalgae
      with different cell wall characteristics. C. reinhardtii is covered by a network
      of fibrils and glycoproteins, while P. lutheri is protected by small cellulose
      scales, and the picoplankton N. oculata by a rigid cellulose wall. The objective
      of this work was to determine to what extent the different components of these
      microorganisms (proteins, carbohydrates, lipids) can be distinguished by 13C
      solid-state NMR with an emphasis on isolating the signature of their cell walls
      and membrane lipid constituents. By using NMR experiments which select rigid or
      mobile zones, as well as 13C-enriched microalgal cells, we improved the spectral
      resolution and simplified the highly crowded spectra. Interspecies differences in
      cell wall constituents, storage sugars and membrane lipid compositions were thus
      evidenced. Carbohydrates from the cell walls could be distinguished from those
      incorporated into sugar reserves or glycolipids. Lipids from the plasmalemma and
      organelle membranes and from storage vacuoles could also be identified. This work
      establishes a basis for a complete characterization of phytoplankton cells by
      solid-state NMR.

PMID- 25065669
TI  - A survey of detergents for the purification of stable, active human cystic
      fibrosis transmembrane conductance regulator (CFTR).
AB  - Structural knowledge of the cystic fibrosis transmembrane conductance regulator
      (CFTR) requires developing methods to purify and stabilize this aggregation-prone
      membrane protein above 1mg/ml. Starting with green fluorescent protein- and
      epitope-tagged human CFTR produced in mammalian cells known to properly fold and
      process CFTR, we devised a rapid tandem affinity purification scheme to minimize
      CFTR exposure to detergent in order to preserve its ATPase function. We compared
      a panel of detergents, including widely used detergents (maltosides, neopentyl
      glycols (MNG), C12E8, lysolipids, Chaps) and innovative detergents (branched
      alkylmaltosides, facial amphiphiles) for CFTR purification, function,
      monodispersity and stability. ATPase activity after reconstitution into
      proteoliposomes was 2-3 times higher when CFTR was purified using facial
      amphiphiles. ATPase activity was also demonstrated in purified CFTR samples
      without detergent removal using a novel lipid supplementation assay. By electron
      microscopy, negatively stained CFTR samples were monodisperse at low
      concentration, and size exclusion chromatography showed a predominance of monomer
      even after CFTR concentration above 1mg/ml. Rates of CFTR aggregation quantified
      in an electrophoretic mobility shift assay showed that detergents which best
      preserved reconstituted ATPase activity also supported the greatest stability,
      with CFTR monomer half-lives of 6-9days in MNG or Chaps, and 12-17days in facial
      amphiphile. Cryoelectron microscopy of concentrated CFTR in MNG or facial
      amphiphile confirmed mostly monomeric protein, producing low resolution
      reconstructions in conformity with similar proteins. These protocols can be used
      to generate samples of pure, functional, stable CFTR at concentrations amenable
      to biophysical characterization. 

PMID- 25065671
TI  - Chronic nandrolone administration promotes oxidative stress, induction of pro
      inflammatory cytokine and TNF-alpha mediated apoptosis in the kidneys of CD1
      treated mice.
AB  - Nandrolone decanoate administration and strenuous exercise increase the extent of
      renal damage in response to renal toxic injury. We studied the role played by
      oxidative stress in the apoptotic response caused by nandrolone decanoate in the
      kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity,
      glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde
      (MDA) were determined after nandrolone treatment. An immunohistochemical study
      and Western blot analysis were performed to evaluate cell apoptosis and to
      measure the effects of renal expression of inflammatory mediators (IL-1beta, TNF
      alpha) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative
      damage in the kidneys of treated mice is shown by an increase in MDA levels and
      by a reduction of antioxidant enzyme GR and GPx activities, resulting in the
      kidney's reduced radical scavenging ability. Renal specimens of the treated group
      showed relevant glomeruli alterations and increased immunostaining and protein
      expressions, which manifested significant focal segmental glomerulosclerosis. The
      induction of proinflammatory cytokine expression levels was confirmed by Western
      blot analysis. Long-term administration of nandrolone promotes oxidative injury
      in the mouse kidneys. TNF-alpha mediated injury due to nandrolone in renal cells
      appears to play a role in the activation of both the intrinsic and extrinsic
      apoptosis pathways. 

PMID- 25065672
TI  - Biocontrol of post-harvest Alternaria alternata decay of cherry tomatoes with
      rhamnolipids and possible mechanisms of action.
AB  - BACKGROUND: Rhamnolipids were reported to have evident antifungal activity. The
      efficacy of rhamnolipids against Alternaria alternata and their possible
      mechanisms involved were investigated. RESULT: The decay incidences of A.
      alternata of cherry tomatoes (Lycopersicon esculentum) treated by rhamnolipids
      were significantly reduced. The in vitro assays showed that rhamnolipids
      inhibited fungal growth on solid medium and prevented spore germination and
      mycelium growth in liquid medium. In addition, the combination of rhamnolipids
      and essential oil had a synergistic effect leading to the decrease of fungicidal
      concentrations of laurel oil. Scanning electron microscopy and transmission
      electron microscopy observations of the pathogen revealed significant
      morphological and cell structural alterations in the hyphae. Compared to the
      control, the content of nucleic acid in supernatant of the suspension of A.
      alternata increased, while the content of DNA and protein of mycelium decreased,
      which was in agreement with electrolyte leakage experiments. CONCLUSION:
      Rhamnolipids could be an alternative to chemicals for controlling post-harvest
      phytopathogenic fungi on fruits and vegetables.

PMID- 25065673
TI  - Ribose-protonated DNA base excision repair: a combined theoretical and
      experimental study.
AB  - Living organisms protect the genome against external influences by recognizing
      and repairing damaged DNA. A common source of gene mutation is the oxidized
      guanine, which undergoes base excision repair through cleavage of the glycosidic
      bond between the ribose and the nucleobase of the lesion. We unravel the repair
      mechanism utilized by bacterial glycosylase, MutM, using quantum-chemical
      calculations involving more than 1000 atoms of the catalytic site. In contrast to
      the base-protonated pathway currently favored in the literature, we show that the
      initial protonation of the lesion's ribose paves the way for an almost barrier
      free glycosidic cleavage. The combination of theoretical and experimental data
      provides further insight into the selectivity and discrimination of MutM's
      binding site toward various substrates. 

PMID- 25065674
TI  - AMP-activated protein kinase mediates the antioxidant effects of resveratrol
      through regulation of the transcription factor FoxO1.
AB  - Numerous physiological functions are controlled by redox-responsive signaling
      pathways. Disruption of redox balance by oxidative stress is recognized as a
      major cause of many pathological conditions, including aging, highlighting the
      importance of investigating how antioxidants maintain redox homeostasis. AMP
      activated protein kinase (AMPK) is activated in response to cellular conditions
      that accompany energy depletion and plays a central role in the regulation of
      energy homeostasis, tumorigenesis and longevity. Recently, several antioxidants
      have been reported to activate AMPK, although the mechanisms by which AMPK acts
      to adjust the levels of cellular reactive oxygen species are not fully
      characterized. In the present study, we investigated the role of AMPK in
      mediating resveratrol-induced antioxidant effects and the molecular mechanisms
      underlying its actions. We demonstrate that AMPK activity plays an indispensable
      role in the operation of the ROS defense system by inducing the expression of the
      antioxidant enzymes, manganese superoxide dismutase and catalase, in response to
      resveratrol or the AMPK agonist 5-aminoimidazole-4-carboxamide-1-beta-d
      ribonucleotide. In addition, we identified the mechanism involved in the
      antioxidant function of AMPK, demonstrating that AMPK directly phosphorylates
      human FoxO1 (forkhead box O1) at Thr(649) in vitro and increases FoxO1-dependent
      transcription of manganese superoxide dismutase and catalase. Mutagenesis studies
      showed that this AMPK-mediated phosphorylation of FoxO1 is critical for FoxO1
      stability and nuclear localization, establishing the molecular basis for the
      induction of FoxO1 transcriptional activity. Our results reveal a novel FoxO1
      dependent mechanism by which AMPK controls the expression of antioxidant enzymes
      and suggest that AMPK has an important role in maintaining redox homeostasis.

PMID- 25065675
TI  - Towards a cognitive model of hallucinations in the course of alcohol dependence?
      A source monitoring-based pilot study.
AB  - BACKGROUND: We investigated whether source-monitoring deficits (here a
      discrimination between imagined and performed actions) underlie hallucinations
      among patients with a history of hallucinations in the course of their alcohol
      dependence. METHOD: We assessed 29 patients with alcohol dependence who had no
      history of hallucinations during their course of alcoholism and 29 patients with
      a history of at least one episode of hallucinations of any modality during their
      course of alcohol dependency. The control group consisted of 24 healthy
      participants. Participants were assessed with an action memory task. Simple
      actions were presented to the participants verbally or non-verbally. Some actions
      were performed physically and others were imagined. In the recognition phase,
      participants were asked whether the action was presented verbally or non-verbally
      (action presentation type discrimination) and whether the action was performed or
      imagined (self-monitoring). A confidence score related to self-monitoring
      responses was also obtained. RESULTS: Alcoholics with a history of hallucinations
      misremembered imagined actions as perceived ones more frequently than patients
      without hallucinations, but not the reverse. Only patients with a history of
      hallucinations committed more errors of this type than healthy subjects. There
      were no group differences regarding discrimination between an action presentation
      type. Both clinical groups committed errors with a higher degree of confidence
      than healthy subjects. CONCLUSIONS: Our results tentatively suggest that a
      specific type of source-monitoring deficit (i.e., confusing imagery with reality)
      may be involved in the hallucinations in patients with alcohol dependence. The
      findings are discussed in the light of a transdiagnostic approach to
      hallucinations.

PMID- 25065676
TI  - Understanding process in group cognitive behaviour therapy for psychosis.
AB  - BACKGROUND: Group cognitive behaviour therapy for psychosis (GCBTp) has shown to
      be effective in diminishing symptoms, as well as in improving other psychosocial
      dimensions such as self-esteem. But little is known regarding the processes that
      generate these therapeutic improvements and might be harnessed to further improve
      its effectiveness. OBJECTIVES: The current study aimed at investigating these
      processes, particularly those linked to interpersonal relationships. DESIGN: The
      participants were all assessed at baseline, were given 24 sessions of GCBTp over
      the course of 3 months and were assessed again at post-treatment as well as 6
      months later (9 months from baseline). METHOD: Sixty-six individuals with early
      psychosis took part in a study of GCBTp where therapist alliance and group
      cohesion were assessed at three time points during the therapy, and punctual
      (each session) self-perceptions on symptoms and optimism were collected. RESULTS:
      Improvements in symptoms (BPRS), self-esteem (SERS-SF) and in self-perceived
      therapeutic improvements (CHOICE) were linked to specific aspects of the
      alliance, group cohesion, as well as optimism. The variables retained were not
      always overall scores, suggesting the importance of the variables at key moments
      during the therapy. CONCLUSIONS: The results clearly demonstrate the importance
      of the alliance and group cohesion, together significantly explaining
      improvements measured at post-therapy or follow-up. PRACTITIONER POINTS: This
      study has attempted to focus mostly on relational aspects, as well as on self
      perceptions, in the context of a GCBTp for individuals with early psychosis. This
      study also showed that these therapeutic relationships are especially useful when
      they are more stable and at specific moments during the therapy, namely when more
      difficult psychological work is done.

PMID- 25065677
TI  - Hydroxyl radical as an unlikely key intermediate in the photodegradation of
      emerging pollutants.
AB  - In this work, a kinetic model, in combination with time-resolved experiments, is
      applied to assess the involvement of .OH in the photodegradation of emerging
      pollutants (EPs) by means of advanced oxidation processes. In contrast with the
      general assumption, quenching of the short-lived .OH in the real waters by the
      (highly diluted) EPs must be very inefficient, so removal of EPs cannot purely
      rely on the generation and reaction of .OH. This suggests that more complex
      pathways have to be considered to explain the photodegradation of EPs actually
      achieved under the employed oxidative conditions, possibly involving other
      reactive species with longer lifetimes or chain degradation processes. 

PMID- 25065678
TI  - Studies on the reaction of trans-2-heptenal with peanut proteins.
AB  - Hexanal, 2-heptenal, and nonanal were identified as relevant reaction products
      formed in the course of the lipid peroxidation of heated peanut oil. For the
      identification of potential amino acid side chain adducts, kinetic studies
      between N(alpha)-benzoylglycyl-l-lysine as a model for protein-bound lysine and
      trans-2-heptenal were performed, showing a strong decrease of the lysine
      derivative whereupon the loss of trans-2-heptenal was moderate. Following acid
      hydrolysis of the incubation mixture of N(alpha)-acetyl-l-lysine and trans-2
      heptenal, two UV-active major lipation products were observed, isolated and
      identified as isomeric pyridinium-derivatives, namely (Z)- and (E)-1-(5-amino-5
      carboxypentyl)-4-butyl-3-(pent-1-en-1-yl)pyridin-1-ium (cis- and trans-BPP
      lysine). After heating of a native peanut protein extract with trans-2-heptenal,
      both derivatives were quantitated by LC-ESI-MS/MS after acid hydrolysis and the
      modification of lysine was measured by amino acid analysis. At low, "food
      relevant", concentrations of trans-2-heptenal, up to 80% of the lysine
      modification could be explained by the formation of cis- and trans-BPP-lysine,
      showing that these two lipation derivatives represent good markers for a protein
      modification by the lipid peroxidation product trans-2-heptenal. 

PMID- 25065679
TI  - Glucose series complexity in hypertensive patients.
AB  - Nonlinear methods have been applied to the analysis of biological signals.
      Complexity analysis of glucose time series may be a useful tool for the study of
      the initial phases of glucoregulatory dysfunction. This observational, cross
      sectional study was performed in patients with essential hypertension. Glucose
      complexity was measured with detrended fluctuation analysis (DFA), and glucose
      variability was measured by the mean amplitudes of glycemic excursion (MAGE). We
      included 91 patients with a mean age of 59 +/- 10 years. We found significant
      correlations for the number of metabolic syndrome (MS)-defining criteria with DFA
      (r = 0.233, P = .026) and MAGE (r = 0.396, P < .0001). DFA differed significantly
      between patients who complied with MS and those who did not (1.44 vs. 1.39, P =
      .018). The MAGE (f = 5.3, P = .006), diastolic blood pressures (f = 4.1, P =
      .018), and homeostasis model assessment indices (f = 4.2, P = .018) differed
      between the DFA tertiles. Multivariate analysis revealed that the only
      independent determinants of the DFA values were MAGE (beta coefficient = 0.002,
      95% confidence interval: 0.001-0.004, P = .001) and abdominal circumference (beta
      coefficient = 0.002, 95% confidence interval: 0.000015-0.004, P = .048). In our
      population, DFA was associated with MS and a number of MS criteria. Complexity
      analysis seemed to be capable of detecting differences in variables that are
      arguably related to the risk of the development of type 2 diabetes.

PMID- 25065680
TI  - Ventricular-arterial coupling in obstructive sleep apnea.
AB  - Arterial elastance (Ea) and systolic elastance are important parameters
      determining effective functional interaction of heart and vessels. The aims of
      this study were to (1) compare arterial (arterial elastance index [EaI]) and
      ventricular (end-systolic elastance [Ees] and end-diastolic elastance [Eed])
      elastance in subjects with obstructive sleep apnea (OSA) and patients with
      treated 'high-risk' hypertension (HHT) and (2) test whether these parameters in
      OSA patients can be improved by continuous positive airway pressure (CPAP)
      therapy. Echocardiographic parameters of cardiac and vascular stiffness (EaI,
      Ees, and Eed) were quantified in 28 patients with OSA (mean [standard deviation],
      age 51 [11] years; 79% male) and 28 treated subjects with HHT (mean [standard
      deviation], age 48 [12] years; 61% male). Twenty-three OSA patients were treated
      with CPAP for median of 26 weeks. Ea was calculated from stroke volume and
      systolic BP and adjusted by body area (EaI). Both study groups had preserved and
      comparable left ventricle contractility. There was no significant differences in
      EaI (P = .94), Ees (P = .5), Eed (P = .63), and arterial-ventricular interaction
      (P = .62) between OSA and HHT groups. After CPAP therapy, there was a significant
      reduction in EaI (paired t test, P = .013) and arterial-ventricular interaction
      (paired t test, P = .004). Ees (P = .17) and Eed (P = .66) parameters did not
      change significantly. OSA and HHT patients have similar parameters of elastance
      and ventricular-arterial coupling. CPAP treatment in OSA patients significantly
      improved ventricular-arterial coupling.

PMID- 25065681
TI  - Clinical predictors and impact of ambulatory blood pressure monitoring in
      pediatric hypertension referrals.
AB  - Elevated blood pressure (BP) is rising in children. Significant proportions of
      children have reactive hypertension or masked hypertension, making ambulatory BP
      monitoring (ABPM) a valuable tool, although with potential economic implications.
      In youth referred for elevated BP, we sought clinic BP combinations that obviated
      the need for ABPM and to specify the economic role of ABPM. In a retrospective
      pediatric referral cohort (N = 170), we examine clinic systolic BP (SBP)
      predictors of components of ABPM hypertension and their combination. In economic
      analyses, we compared effectiveness and charges of three diagnostic pathways: (1)
      clinic BP alone; (2) abnormal clinic BP prompting ABPM; or (3) universal ABPM.
      ABPM hypertension occurred in 55 (32.4%) and reactive hypertension in 37 (21.8%),
      average automated (beta = 0.208; 95% confidence interval, 0.027, 0.389; P = .03)
      and maximum auscultatory clinic SBP (beta = 0.160; 95% confidence interval 0.022,
      0.299; P = .02) were associated with ABPM SBP mean, but none predicted SBP load.
      No clinic SBP combination was associated with ABPM hypertension. Universal ABPM
      accrued the lowest average charge per hypertensive youth identified ($10,948). We
      did not identify a clinic SBP combination that predicted ABPM hypertension in
      youth referred for elevated BP. Universal ABPM, in this context, may be the most
      economically and clinically efficient diagnostic strategy.

PMID- 25065682
TI  - Retinal and nonocular abnormalities in Cyp27a1(-/-)Cyp46a1(-/-) mice with
      dysfunctional metabolism of cholesterol.
AB  - Cholesterol elimination from nonhepatic cells involves metabolism to side-chain
      oxysterols, which serve as transport forms of cholesterol and bioactive molecules
      modulating a variety of cellular processes. Cholesterol metabolism is tissue
      specific, and its significance has not yet been established for the retina, where
      cytochromes P450 (CYP27A1 and CYP46A1) are the major cholesterol-metabolizing
      enzymes. We generated Cyp27a1(-/-)Cyp46a1(-/-) mice, which were lean and had
      normal serum cholesterol and glucose levels. These animals, however, had changes
      in the retinal vasculature, retina, and several nonocular organs (lungs, liver,
      and spleen). Changes in the retinal vasculature included structural abnormalities
      (retinal-choroidal anastomoses, arteriovenous shunts, increased permeability,
      dilation, nonperfusion, and capillary degeneration) and cholesterol deposition
      and oxidation in the vascular wall, which also exhibited increased adhesion of
      leukocytes and activation of the complement pathway. Changes in the retina
      included increased content of cholesterol and its metabolite, cholestanol, which
      were focally deposited at the apical and basal sides of the retinal pigment
      epithelium. Retinal macrophages of Cyp27a1(-/-)Cyp46a1(-/-) mice were activated,
      and oxidative stress was noted in their photoreceptor inner segments. Our
      findings demonstrate the importance of retinal cholesterol metabolism for
      maintenance of the normal retina, and suggest new targets for diseases affecting
      the retinal vasculature. 

PMID- 25065683
TI  - Interferon-gamma protects first-trimester decidual cells against aberrant matrix
      metalloproteinases 1, 3, and 9 expression in preeclampsia.
AB  - Human extravillous trophoblast (EVT) invades the decidua via integrin receptors
      and subsequently degrades extracellular matrix proteins. In preeclampsia (PE),
      shallow EVT invasion elicits incomplete spiral artery remodeling, causing reduced
      uteroplacental blood flow. Previous studies show that preeclamptic decidual
      cells, but not interstitial EVTs, display higher levels of extracellular matrix
      degrading matrix metalloproteinase (MMP)-9, but not MMP-2. Herein, we extend our
      previous PE-related assessment of MMP-2 and MMP-9 to include MMP-1, which
      preferentially degrades fibrillar collagens, and MMP-3, which can initiate a
      local proteolytic cascade. In human first-trimester decidual cells incubated with
      estradiol, tumor necrosis factor-alpha (TNF-alpha) significantly enhanced MMP-1,
      MMP-3, and MMP-9 mRNA and protein levels and activity measured by real-time
      quantitative RT-PCR, ELISA, immunoblotting, and zymography, respectively. In
      contrast, interferon gamma (IFN-gamma) reversed these effects and
      medroxyprogesterone acetate elicited further reversal. Immunoblotting revealed
      that p38 mitogen-activated protein kinase signaling mediated TNF-alpha
      enhancement of MMP-1, MMP-3, and MMP-9, whereas IFN-gamma inhibited p38 mitogen
      activated protein kinase phosphorylation. Unlike highly regulated MMP-1, MMP-3,
      and MMP-9, MMP-2 mRNA and protein expression was constitutive in decidual cells.
      Because inflammation underlies PE-associated shallow EVT invasion, these results
      suggest that excess macrophage-derived TNF-alpha augments expression of MMP-1,
      MMP-3, and MMP-9 in decidual cells to interfere with normal stepwise EVT invasion
      of the decidua. In contrast, decidual natural killer cell-derived IFN-gamma
      reverses such TNF-alpha-induced MMPs to protect against PE. 

PMID- 25065684
TI  - Astrocyte elevated gene-1 and c-Myc cooperate to promote hepatocarcinogenesis in
      mice.
AB  - Astrocyte elevated gene-1 (AEG-1) and c-Myc are overexpressed in human
      hepatocellular carcinoma (HCC) functioning as oncogenes. AEG-1 is
      transcriptionally regulated by c-Myc, and AEG-1 itself induces c-Myc by
      activating the Wnt/beta-catenin-signaling pathway. We now document the
      cooperation of AEG-1 and c-Myc in promoting hepatocarcinogenesis by analyzing
      hepatocyte-specific transgenic mice expressing either AEG-1 (albumin [Alb]/AEG
      1), c-Myc (Alb/c-Myc), or both (Alb/AEG-1/c-Myc). Wild-type and Alb/AEG-1 mice
      did not develop spontaneous HCC. Alb/c-Myc mice developed spontaneous HCC without
      distant metastasis, whereas Alb/AEG-1/c-Myc mice developed highly aggressive HCC
      with frank metastasis to the lungs. Induction of carcinogenesis by N
      nitrosodiethylamine significantly accelerated the kinetics of tumor formation in
      all groups. However, in Alb/AEG-1/c-Myc, the effect was markedly pronounced with
      lung metastasis. In vitro analysis showed that Alb/AEG-1/c-Myc hepatocytes
      acquired increased proliferation and transformative potential with sustained
      activation of prosurvival and epithelial-mesenchymal transition-signaling
      pathways. RNA-sequencing analysis identified a unique gene signature in livers of
      Alb/AEG-1/c-Myc mice that was not observed when either AEG-1 or c-Myc was
      overexpressed. Specifically, Alb/AEG-1/c-Myc mice overexpressed maternally
      imprinted noncoding RNAs (ncRNAs), such as Rian, Meg-3, and Mirg, which are
      implicated in hepatocarcinogenesis. Knocking down these ncRNAs significantly
      inhibited proliferation and invasion by Alb/AEG-1/c-Myc hepatocytes. CONCLUSION:
      Our studies reveal a novel cooperative oncogenic effect of AEG-1 and c-Myc that
      might explain the mechanism of aggressive HCC. Alb/AEG-1/c-Myc mice provide a
      useful model to understand the molecular mechanism of cooperation between these
      two oncogenes and other molecules involved in hepatocarcinogenesis. This model
      might also be of use for evaluating novel therapeutic strategies targeting HCC.

PMID- 25065685
TI  - Oral immunization of haemaggulutinin H5 expressed in plant endoplasmic reticulum
      with adjuvant saponin protects mice against highly pathogenic avian influenza A
      virus infection.
AB  - Pandemics in poultry caused by the highly pathogenic avian influenza (HPAI) A
      virus occur too frequently globally, and there is growing concern about the HPAI
      A virus due to the possibility of a pandemic among humans. Thus, it is important
      to develop a vaccine against HPAI suitable for both humans and animals. Various
      approaches are underway to develop such vaccines. In particular, an edible
      vaccine would be a convenient way to vaccinate poultry because of the behaviour
      of the animals. However, an edible vaccine is still not available. In this study,
      we developed a strategy of effective vaccination of mice by the oral
      administration of transgenic Arabidopsis plants (HA-TG) expressing haemagglutinin
      (HA) in the endoplasmic reticulum (ER). Expression of HA in the ER resulted in
      its high-level accumulation, N-glycosylation, protection from proteolytic
      degradation and long-term stability. Oral administration of HA-TG with saponin
      elicited high levels of HA-specific systemic IgG and mucosal IgA responses in
      mice, which resulted in protection against a lethal influenza virus infection
      with attenuated inflammatory symptoms. Based on these results, we propose that
      oral administration of freeze-dried leaf powders from transgenic plants
      expressing HA in the ER together with saponin is an attractive strategy for
      vaccination against influenza A virus. 

PMID- 25065686
TI  - DNA aptamers are functional molecular recognition sensors in protic ionic
      liquids.
AB  - The function and structural changes of an AMP molecular aptamer beacon and its
      molecular recognition capacity for its target, adenosine monophosphate (AMP), was
      systematically explored in solution with a protic ionic liquid, ethylammonium
      nitrate (EAN). It could be proven that up to 2 M of EAN in TBS buffer, the AMP
      molecular aptamer beacon was still capable of recognizing AMP while also
      maintaining its specificity. The specificity was proven by using the guanosine
      monophosphate (GMP) as target; GMP is structurally similar to AMP but was not
      recognized by the aptamer. We also found that in highly concentrated EAN
      solutions the overall amount of double stranded DNA formed, as well as its
      respective thermal stability, diminished gradually, but surprisingly the
      hybridization rate (kh ) of single stranded DNA was significantly accelerated in
      the presence of EAN. The latter may have important implications in DNA technology
      for the design of biosensing and DNA-based nanodevices in nonconventional
      solvents, such as ionic liquids. 

PMID- 25065687
TI  - Diagnostic sensitivity of bone scintigraphy for equine stifle disorders.
AB  - Disorders of the stifle are a common cause of lameness in horses yet the accuracy
      of scintigraphy for diagnosis of stifle conditions is controversial. The aim of
      retrospective cross-sectional study was to determine the diagnostic sensitivity
      (Se) of bone scintigraphy in detecting stifle disease and to determine if two
      orthogonal scintigraphic images improve diagnostic Se. Horses that underwent
      scintigraphic examination during a two-year period were included. Horses were
      divided into two groups: group 1 (N = 23) had lameness that was localized to the
      stifle by intra-articular analgesia and group 2 (N = 182) had lameness that was
      localized to a different location. Scintigraphic studies (one image or two
      images) were independently and retrospectively analyzed by two radiologists (R1
      and R2). Sensitivity, specificity (Sp) and predictive values (PV), and were
      calculated for each type of study (one image or two images) and for each
      radiologist (R1 or R2). The Se to detect stifle disorders varied between
      radiologists (29.2% and 20.8%). The Sp was 84.5% and 88.3%. When two images were
      evaluated a decrease in the positive PV for both readers occurred. The Cohen
      kappa coefficient (kappa) between readers was poor when one image (0.084) or two
      images (0.117) were evaluated. Findings from this study indicated that bone-phase
      nuclear scintigraphy is reasonably specific but highly insensitive for detecting
      lameness originating from the stifle in a diverse population of both normal and
      affected horses. The addition of a caudal scintigraphic image acquisition did not
      improve diagnostic sensitivity. 

PMID- 25065688
TI  - Interspecific hybridization and bioactive alkaloid variation increases diversity
      in endophytic Epichloe species of Bromus laevipes.
AB  - Studying geographic variation of microbial mutualists, especially variation in
      traits related to benefits they provide their host, is critical for understanding
      how these associations impact key ecological processes. In this study, we
      investigate the phylogenetic population structure of Epichloe species within
      Bromus laevipes, a native cool-season bunchgrass found predominantly in
      California. Phylogenetic classification supported inference of three distinct
      Epichloe taxa, of which one was nonhybrid and two were interspecific hybrids.
      Inheritance of mating-type idiomorphs revealed that at least one of the hybrid
      species arose from independent hybridization events. We further investigated the
      geographic variation of endophyte-encoded alkaloid genes, which is often
      associated with key benefits of natural enemy protection for the host. Marker
      diversity at the ergot alkaloid, loline, indole-diterpene, and peramine loci
      revealed four alkaloid genotypes across the three identified Epichloe species.
      Predicted chemotypes were tested using endophyte-infected plant material that
      represented each endophyte genotype, and 11 of the 13 predicted alkaloids were
      confirmed. This multifaceted approach combining phylogenetic, genotypic, and
      chemotypic analyses allowed us to reconstruct the diverse evolutionary histories
      of Epichloe species present within B. laevipes and highlight the complex and
      dynamic processes underlying these grass-endophyte symbioses. 

PMID- 25065689
TI  - Anti-inflammatory activity of iridoid and catechol derivatives from Eucommia
      ulmoides Oliver.
AB  - Neuroinflammation and pro-inflammatory mediators play key roles in the
      pathogenesis of neurodegenerative diseases including stroke, which account for a
      significant burden of morbidity and mortality worldwide. Recently, the
      unsatisfactory pharmacotherapy and side effects of the drugs led to the
      development of alternative medicine for treating these diseases. Du Zhong (DZ),
      Eucommia ulmoides Oliver leaves, is a commonly used herb in the therapy of stroke
      in China. We hypothesize that the components from DZ inhibit neuroinflammation.
      In this study, DZ was extracted and the bioactive fractions with inhibitory
      effect on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV
      2 microglial cells were further separated using chromatography. Two purified
      bioactive compounds, genipin (compound C) and 4-(1,2-dimethoxyethyl)benzene-1,2
      diol (compound F), were isolated and identified after spectroscopic analysis. The
      results showed that they inhibited LPS-stimulated NO and tumor necrosis factor
      alpha (TNF-alpha) production. Genipin exerted its anti-inflammatory effects
      through PI3K/Akt signaling pathway, whereas compound F inhibited phosphorylation
      of p38 mitogen-activated protein kinase (MAPK). In conclusion, genipin and
      compound F have potential for developing into new drugs for treating
      neurodegenerative diseases. 

PMID- 25065690
TI  - Preliminary Investigations on the Distribution of Leptospira Serovars in Domestic
      Animals in North-west Morocco.
AB  - Leptospirosis is a neglected zoonosis of global importance with a complex
      epidemiology that affects humans, domestic and wild mammals. However, due to the
      diversity of clinical signs and difficulties of establishing a confirmatory
      laboratory diagnosis, the disease remains poorly investigated, particularly in
      the developing world. In Morocco, a descriptive study of the seroprevalence of
      Leptospira infection in animals has never been undertaken. To fill this gap, the
      current study was conducted on a subset of animals in north-west Morocco as a
      preliminary step towards understanding the epidemiological patterns of animal
      leptospirosis in the country. The study was conducted on 289 serum samples
      collected between January and April 2012 from dogs, cattle, sheep, goats and
      donkeys in the areas of Rabat-Temara, Sidi Kacem and Oulmes. All serum samples
      were tested by the MAT with 14 reference strains of the most prevalent pathogenic
      serovars of Leptospira and two serovars of non-pathogenic Leptospira. The overall
      seroprevalence of Leptospira in cattle, sheep, goats, dogs and donkeys was 15%,
      18%, 20%, 21% and 20%, respectively. The most prevalent serogroups found in each
      species were Ballum, Sejroe, and Australis in cattle, Ballum, Australis and
      Sejroe in sheep, Australis and Ballum in goats, Javanica and Australis in donkey
      and Australis, Ballum and Canicola in dogs. Of all the serogroups tested in this
      study, Icterohaemorrhagiae, the only serogroup which has been previously reported
      in humans in Morocco, was rarely reactive. The majority of reactive sera were
      collected from low land areas. A large number of sera samples classified as
      seronegative when tested against pathogenic leptospires were positive when tested
      against non-pathogenic leptospires; this is suggestive of possible novel, as yet
      unclassified, Leptospira serovars in Morocco. Eleven of thirteen sheep urine
      samples were positive by real-time PCR confirming their role as Leptospira
      carriers in Morocco. 

PMID- 25065691
TI  - Age distribution of childhood thyroid cancer patients in Ukraine after Chernobyl
      and in Fukushima after the TEPCO-Fukushima Daiichi NPP accident.

PMID- 25065692
TI  - Allowing for non-adherence to treatment in a randomized controlled trial of two
      antidepressants (citalopram versus reboxetine): an example from the GENPOD trial.
AB  - BACKGROUND: Meta-analyses suggest that reboxetine may be less effective than
      other antidepressants. Such comparisons may be biased by lower adherence to
      reboxetine and subsequent handling of missing outcome data. This study
      illustrates how to adjust for differential non-adherence and hence derive an
      unbiased estimate of the efficacy of reboxetine compared with citalopram in
      primary care patients with depression. METHOD: A structural mean modelling (SMM)
      approach was used to generate adherence-adjusted estimates of the efficacy of
      reboxetine compared with citalopram using GENetic and clinical Predictors Of
      treatment response in Depression (GENPOD) trial data. Intention-to-treat (ITT)
      analyses were performed to compare estimates of effectiveness with results from
      previous meta-analyses. RESULTS: At 6 weeks, 92% of those randomized to
      citalopram were still taking their medication, compared with 72% of those
      randomized to reboxetine. In ITT analysis, there was only weak evidence that
      those on reboxetine had a slightly worse outcome than those on citalopram
      [adjusted difference in mean Beck Depression Inventory (BDI) scores: 1.19, 95%
      confidence interval (CI) -0.52 to 2.90, p = 0.17]. There was no evidence of a
      difference in efficacy when differential non-adherence was accounted for using
      the SMM approach for mean BDI (-0.29, 95% CI -3.04 to 2.46, p = 0.84) or the
      other mental health outcomes. CONCLUSIONS: There was no evidence of a difference
      in the efficacy of reboxetine and citalopram when these drugs are taken and
      tolerated by depressed patients. The SMM approach can be implemented in standard
      statistical software to adjust for differential non-adherence and generate
      unbiased estimates of treatment efficacy for comparisons of two (or more) active
      interventions.

PMID- 25065693
TI  - The anti-inflammatory effect of cherry blossom extract (Prunus yedoensis) used in
      soothing skincare product.
AB  - OBJECTIVE: Previous investigations suggested that cherry blossoms could provide
      valuable bioactive materials. However, few observations regarding the anti
      inflammatory effect of cherry blossoms were reported. This study was to explore
      the anti-inflammatory effect of cherry blossom extract (CBE), which was used as a
      soothing ingredient in skincare product. METHODS: In vitro study, the anti
      inflammatory effect of CBE on the nitric oxide (NO) inhibition assay in
      lipopolysaccharide (LPS)-treated RAW 264.7 cells was investigated. In vivo study,
      40 volunteers were included in a randomized, single-blinded, placebo-controlled
      trial. 24-hour-occlusive test chambers were applied on the flexor side of the
      forearm with 3% sodium lauryl sulphate (SLS). Subsequently, the test areas were
      treated on 9 subsequent days with a cream containing 3% CBE or a placebo.
      Evaluation included a visual score and determination of erythema value (E value).
      RESULTS: In vitro study, 2% CBE reduced NO production by 31.83% compared to the
      placebo. In the SLS irritant patch test, the visual score and erythema value of
      CBE were lower than that of the placebo on D5 and D9. CONCLUSION: Cherry blossom
      extract shows good anti-inflammatory effect in vitro and in vivo and represents a
      promising functional ingredient in soothing skincare product by reducing skin
      inflammation.

PMID- 25065694
TI  - IgG4-related skin disease.
AB  - IgG4-related disease (IgG4-RD) is a recently established clinical entity
      characterized by high levels of circulating IgG4, and tissue infiltration of
      IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change
      involving multiple organs, such as the pancreas and salivary and lacrimal glands.
      The skin lesions of IgG4-RD have been poorly characterized and may stem not only
      from direct infiltration of plasma cells but also from IgG4-mediated
      inflammation. Based on the documented cases together with ours, we categorized
      the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple
      papulonodules or indurations on the trunk and proximal part of the limbs), (2)
      pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and
      papulonodules mainly on the periauricular, cheek and mandible regions), (3)
      Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4)
      psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5)
      unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic
      purpura (bilateral asymmetrical palpable purpuric lesions on the lower
      extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally
      with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene).
      It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+)
      plasma cells, while the other types (4-7) are caused by secondary mechanisms.
      IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin
      lesions that form plaques, nodules or tumours (types 1-3), but may manifest
      secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7). 

PMID- 25065695
TI  - Maltodextrins as chiral selectors in CE: molecular structure effect of basic
      chiral compounds on the enantioseparation.
AB  - Prediction of chiral separation for a compound using a chiral selector is an
      interesting and debatable work. For this purpose, in this study 23 chiral basic
      drugs with different chemical structures were selected as model solutes and the
      influence of their chemical structures on the enantioseparation in the presence
      of maltodextrin (MD) as chiral selector was investigated. For chiral separation,
      a 100-mM phosphate buffer solution (pH 3.0) containing 10% (w/v) MD with dextrose
      equivalent (DE) of 4-7 as chiral selector at the temperature of 25 degrees C and
      voltage of 20 kV was used. Under this condition, baseline separation was achieved
      for nine chiral compounds and partial separation was obtained for another six
      chiral compounds while no enantioseparation was obtained for the remaining eight
      compounds. The results showed that the existence of at least two aromatic rings
      or cycloalkanes and an oxygen or nitrogen atom or -CN group directly bonded to
      the chiral center are necessary for baseline separation. With the obtained
      results in this study, chiral separation of a chiral compound can be estimated
      with MD-modified capillary electrophoresis before analysis. This prediction will
      minimize the number of preliminary experiments required to resolve enantiomers
      and will save time and cost.

PMID- 25065696
TI  - Bazex syndrome (acrokeratosis paraneoplastica).

PMID- 25065698
TI  - The risk of hepatitis B virus reactivation and the role of antiviral prophylaxis
      in hepatitis B surface antigen negative/hepatitis B core antibody positive
      patients with diffuse large B-cell lymphoma receiving rituximab-based
      chemotherapy.
AB  - The risk factors and the role of prophylactic antiviral therapy of hepatitis B
      virus (HBV) reactivation in patients with hepatitis B surface antigen (HBsAg)
      negative/hepatitis B core antibody (HBcAb) positive disease remain controversial.
      We reviewed 629 patients with diffuse large B-cell lymphoma (DLBCL). Among 629
      patients, 150 of 246 patients with resolved HBV (HBsAg negative and HBcAb
      positive) were treated with rituximab-combined therapy. Among these 150 patients,
      none of 104 patients (0.0%) who were hepatitis B surface antibody (HBsAb)
      positive experienced HBV reactivation versus four of 46 patients (8.7%) who were
      HBsAb negative (p = 0.008). One of 113 patients (0.9%) with International
      Prognostic Index (IPI) 0-2 suffered HBV reactivation versus three of the
      remaining 37 patients (8.1%) with IPI 3-5 (p = 0.047). HBsAb and IPI are
      potential risk factors for HBV reactivation. The use of prophylactic agents may
      not be recommended for these patients until the occurrence of HBV reactivation. 

PMID- 25065697
TI  - Effect of yohimbine on reinstatement of operant responding in rats is dependent
      on cue contingency but not food reward history.
AB  - Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous
      studies as a pharmacological stressor in rodents, monkeys and humans. Recently,
      yohimbine has become the most common stress manipulation in studies on
      reinstatement of drug and food seeking. However, the wide range of conditions
      under which yohimbine promotes reward seeking is significantly greater than that
      of stressors like intermittent footshock. Here, we addressed two fundamental
      questions regarding yohimbine's effect on reinstatement of reward seeking: (1)
      whether the drug's effect on operant responding is dependent on previous reward
      history or cue contingency, and (2) whether yohimbine is aversive or rewarding
      under conditions typically used in reinstatement studies. We also used in vivo
      microdialysis to determine yohimbine's effect on dopamine levels in nucleus
      accumbens (NAc) and medial prefrontal cortex (mPFC). We found that the magnitude
      of yohimbine-induced (0.5, 1.0, 2.0 mg/kg) operant responding during the
      reinstatement tests was critically dependent on the contingency between lever
      pressing and discrete tone-light cue delivery but not the previous history with
      food reward during training. We also found that yohimbine (2 mg/kg) did not cause
      conditioned place aversion. Finally, we found that yohimbine modestly increased
      dopamine levels in mPFC but not NAc. Results suggest that yohimbine's effects on
      operant responding in reinstatement studies are likely independent of the history
      of contingent self-administration of food or drug rewards and may not be related
      to the commonly assumed stress-like effects of yohimbine.

PMID- 25065699
TI  - Treating chronic lymphocytic leukemia with a combination of rituximab and
      alemtuzumab: a "successful couple," but are they still relevant together?

PMID- 25065700
TI  - Role of folate status and methylenetetrahydrofolate reductase genotype on the
      toxicity and outcome of induction chemotherapy in children with acute
      lymphoblastic leukemia.
AB  - The effect of serum folate levels and methylenetetrahydrofolate reductase (MTHFR)
      genotype on complications and outcome of induction chemotherapy in 150 children
      with acute lymphoblastic leukemia (ALL) was studied. Folate deficiency in 26% at
      baseline was more common in children with MTHFR 677 mutations. Folate deficient
      children had a higher incidence of neutropenia (p = 0.03), thrombocytopenia (p =
      0.02) and febrile neutropenia (p = 0.01) and higher transfusion requirement
      during induction compared to folate sufficient children. Sepsis related induction
      deaths were more frequent in folate deficient children (p = 0.02) during
      induction. Children with 677 and 1298 mutations had a higher incidence of
      cytopenias (p = 0.01) and mucositis (p = 0.007), the risks of which increased
      with concomitant folate deficiency. A significant fall in folate levels was
      observed post-induction (p = 0.02), most markedly in mutant 677 genotypes.
      Multivariate analysis revealed associations of baseline folate deficiency with
      low counts at day 14 (p = 0.001) and MTHFR 1298 mutations with mucositis (p =
      0.02). 

PMID- 25065701
TI  - Phase II study of first-line (131)I-rituximab radioimmunotherapy in follicular
      non-Hodgkin lymphoma and prognostic (18)F-fluorodeoxyglucose positron emission
      tomography.
AB  - First-line (131)I-anti-CD20 radioimmunotherapy of indolent non-Hodgkin lymphoma
      (NHL) achieves durable remission with low toxicity. The phase II INITIAL study
      comprised 68 patients with follicular NHL followed up to 7 years (median 4 years)
      after outpatient (131)I-rituximab radioimmunotherapy (RIT) in conjunction with
      rituximab, followed by maintenance therapy for 1 year. Baseline and 3-month (18)F
      fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) imaging, analyzed
      according to Deauville criteria, was used to evaluate response and predict
      prognosis. The overall response rate at 3 months was 99%, with 88% achieving
      Deauville category 1-3. These satisfactory responders did not reach median time
      to-next-treatment, versus a median of 29 months for a category 4-5 response (p <
      0.0001). Grade IV hematological toxicity (9%) was self-limited without clinical
      sequelae. (131)I-rituximab radioimmunotherapy in newly diagnosed, advanced stage,
      symptomatic follicular NHL is an effective, practical and affordable alternative
      to existing conventional chemotherapies, with lower toxicity and durable
      remissions. Response assessment at 3 months by (18)F-FDG PET Deauville five-point
      scale permits prognostic stratification. 

PMID- 25065702
TI  - Sirolimus plus calcineurin inhibitors and methotrexate: is more necessarily
      better?

PMID- 25065703
TI  - Successful treatment with reduced-intensity cord blood transplant in a patient
      with relapsed refractory hepatosplenic T-cell lymphoma.

PMID- 25065705
TI  - Four new bis-iridoids isolated from the traditional Tibetan herb Pterocephalus
      hookeri.
AB  - Pterocenoids A-E (1-4), which Pterocenoids A(1) is one novel dimer containing a
      pyridine monoterpene alkaloid; and Pterocenoids B-E (2-4) are rare arranged non
      glycosidic bis-iridoids were isolated from Pterocephlus hookeri. The structures
      of the compounds were established by 1D and 2D NMR spectroscopy and mass
      spectrometry. All bis-iridoids isolated from P. hookeri were found to possess
      secoiridoid/iridoid subtype skeletons. Hence, bis-iridoids can be regarded as the
      chemotaxonomic markers of P. hookeri. The origins of the new bis-iridoids (1-4)
      were postulated and their activities of inhibition of the NF-kappaB pathway were
      assayed and compounds 1-3 showed moderate activity in inhibiting NF-kappaB.

PMID- 25065704
TI  - Summary of the 8th Annual Bladder Cancer Think Tank: Collaborating to move
      research forward.
AB  - OBJECTIVES: The 8th Annual Bladder Cancer Think Tank (BCAN-TT) brought together a
      multidisciplinary group of clinicians, researchers, and patient advocates in an
      effort to advance bladder cancer research. METHODS AND MATERIALS: With the theme
      of "Collaborating to Move Research Forward," the meeting included three panel
      presentations and seven small working groups. RESULTS: The panel presentations
      and interactive discussions focused on three main areas: gender disparities,
      sexual dysfunction, and targeting novel pathways in bladder cancer. Small working
      groups also met to identify projects for the upcoming year, including: (1)
      improving enrollment and quality of clinical trials; (2) collecting data from
      multiple institutions for future research; (3) evaluating patterns of care for
      non-muscle-invasive bladder cancer; (4) improving delivery of care for muscle
      invasive disease; (5) improving quality of life for survivors; (6) addressing
      upper tract disease; and (7) examining the impact of health policy changes on
      research and treatment of bladder cancer. CONCLUSIONS: The goal of the BCAN-TT is
      to advance the care of patients with bladder cancer and to promote collaborative
      research throughout the year. The meeting provided ample opportunities for
      collaboration among clinicians from multiple disciplines, patients and patient
      advocates, and industry representatives.

PMID- 25065706
TI  - Copper-catalysed direct radical alkenylation of alkyl bromides.
AB  - A copper-catalysed direct radical alkenylation of various benzyl bromides and
      alpha-carbonyl alkyl bromides has been developed. Compared with the recent
      radical alkenylations which mostly focused on secondary or tertiary alkyl
      halides, this transformation shows good reactivity to primary alkyl halides and
      tertiary, secondary alkyl halides were also tolerated. The key initiation step of
      this transformation is a copper-induced single-electron reduction of C-Br bonds
      to generate alkyl radical species. 

PMID- 25065708
TI  - Cognitive-behavioural therapy augments the effects of deep brain stimulation in
      obsessive-compulsive disorder.
AB  - BACKGROUND: Deep brain stimulation (DBS) is a promising new treatment for
      patients with treatment-refractory obsessive-compulsive disorder (OCD). However,
      since most DBS patients only show a partial response, the treatment still needs
      to be improved. In this study we hypothesized that cognitive-behavioural therapy
      (CBT) could optimize the post-operative management in DBS and we evaluated the
      efficacy of CBT as augmentation to DBS targeted at the nucleus accumbens. METHOD:
      A total of 16 patients with treatment-refractory OCD were treated with DBS
      targeted at the nucleus accumbens. After stabilization of decline in OCD
      symptoms, a standardized 24-week CBT treatment programme was added to DBS in an
      open-phase trial of 8 months. Changes in obsessive-compulsive, anxiety and
      depressive symptoms were evaluated using the Yale-Brown Obsessive Compulsive
      Scale, Hamilton Anxiety Scale and Hamilton Rating Scale for Depression. RESULTS:
      Following the addition of CBT to DBS, a significant decrease in obsessive
      compulsive symptoms was observed, but not in anxiety and depressive symptoms. In
      a subsequent double-blind phase, in which stimulation was discontinued, OCD
      symptoms returned to baseline (relapse) and anxiety and depressive symptoms
      worsened (rebound) compared with baseline. CONCLUSIONS: The results of this
      explorative study suggest that a combined treatment of accumbens DBS and CBT may
      be optimal for improving obsessive-compulsive symptoms in treatment-refractory
      OCD. However, a subsequent randomized controlled trial is necessary to draw firm
      conclusions. It seems that DBS results in affective changes that may be required
      to enable response prevention in CBT. This may indicate that DBS and CBT act as
      two complementary treatments.

PMID- 25065707
TI  - Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder
      persistence.
AB  - Typhoid (enteric fever) remains a major cause of morbidity and mortality
      worldwide, causing over 21 million new infections annually, with the majority of
      deaths occurring in young children. Because typhoid fever-causing Salmonella have
      no known environmental reservoir, the chronic, asymptomatic carrier state is
      thought to be a key feature of continued maintenance of the bacterium within
      human populations. Despite the importance of this disease to public health, our
      understanding of the molecular mechanisms that catalyze carriage, as well as our
      ability to reliably identify and treat the Salmonella carrier state, have only
      recently begun to advance. 

PMID- 25065709
TI  - Measuring students perceptions of interprofessional clinical placements:
      development of the Interprofessional Clinical Placement Learning Environment
      Inventory.
AB  - Pre-professional healthcare courses, including nursing, are increasingly focused
      on interprofessional learning and experimentation with clinical education in
      'training wards'. This involves students from at least two disciplines who, under
      supervision, are responsible for patients' care. There is no consensus on how
      students' clinical learning experiences in this context are evaluated. We report
      the development and testing of the Interprofessional Clinical Placement Learning
      Environment Inventory (ICPLEI) in the Australian context. A question set was
      developed to measure student's perceptions of key variables in an
      interprofessional clinical learning environment: orientation, supervision, roles,
      learning and autonomy. An expert nursing panel rated items for a Content Validity
      Index of .93. Reliability was tested with 38 students. After a 2-week
      interprofessional ward placement nursing, medical and allied health students (n =
      38) rated their learning environment highly, with median responses 4 or 5 of five
      (mean total 83%). The scale was reliable with a Cronbach alpha of .80 and
      moderate item-to-total correlations for 22/26 items. The Interprofessional
      Clinical Placement Learning Environment Inventory is a reliable, feasible, fast
      to complete tool, suitable for use with pre-registration healthcare students in
      this setting. Further testing of the tool's psychometric properties is
      recommended.

PMID- 25065710
TI  - Impact of lung cancer screening results on participant health-related quality of
      life and state anxiety in the National Lung Screening Trial.
AB  - BACKGROUND: Low-dose computed tomography (LDCT) lung screening has been
      associated with a 20% reduction in lung cancer mortality. A major barrier to the
      adoption of lung screening is the potential negative psychological impact of a
      false-positive (FP) screen, occurring in 20% to 50% of those screened. The
      objective of this study was to assess the impact of abnormal findings on health
      related quality of life (HRQoL) and anxiety in the American College of Radiology
      (ACRIN)/National Lung Screening Trial (NLST). METHODS: The NLST was a randomized
      screening trial comparing LDCT with chest X-ray screening (CXR). This study was
      part of the original protocol. A total of 2812 participants at 16 of 23 ACRIN
      sites who had baseline HRQoL assessments were asked to complete the Short Form-36
      and the State Trait Anxiety Inventory (form Y-1) questionnaires to assess short
      term (1 month) and long-term (6 months) effects of screening. FP were lung cancer
      free at 1 year, and true-positives (TP) were not. RESULTS: Of the total
      participants, 1024 (36.4%) participants were FP, 63 (2.2%) were TP, 344 (12.2%)
      had significant incidental findings (SIFs), and 1381 (49.1%) had negative
      screens. Participants had been randomized to LDCT (n = 1947) and CXR (n = 865).
      Short-term and long-term HRQoL and state anxiety did not differ across
      participants with FP, SIF, or negative screens. Short-term and long-term HRQoL
      were lower and anxiety was higher for TP participants compared to participants
      with FP, SIF, and negative screens. CONCLUSIONS: In a large multicenter lung
      screening trial, participants receiving a false-positive or SIF screen result
      experienced no significant difference in HRQoL or state anxiety at 1 or at 6
      months after screening relative to those receiving a negative result.

PMID- 25065711
TI  - Genetic and environmental influences on cortical surface area and cortical
      thickness in bipolar disorder.
AB  - BACKGROUND: The risk of developing bipolar disorder (BD) has been linked to
      structural brain abnormalities. The degree to which genes and environment
      influence the association of BD with cortical surface area remains to be
      elucidated. In this twin study, genetic and environmental contributions to the
      association between liability to develop BD and surface area, thickness and
      volume of the cortex were examined. METHOD: The study cohort included 44 affected
      monozygotic (nine concordant, 12 discordant) and dizygotic (four concordant, 19
      discordant) twin pairs, and seven twins from incomplete discordant monozygotic
      and dizygotic discordant twin pairs. In addition, 37 monozygotic and 24 dizygotic
      healthy control twin pairs, and six twins from incomplete monozygotic and
      dizygotic control pairs were included. RESULTS: Genetic liability to develop BD
      was associated with a larger cortical surface in limbic and parietal regions, and
      a thicker cortex in central and parietal regions. Environmental factors related
      to BD were associated with larger medial frontal, parietal and limbic, and
      smaller orbitofrontal surfaces. Furthermore, thinner frontal, limbic and
      occipital cortex, and larger frontal and parietal, and smaller orbitofrontal
      volumes were also associated with environmental factors related to BD.
      CONCLUSIONS: Our results suggest that unique environmental factors play a
      prominent role in driving the associations between liability to develop BD and
      cortical measures, particularly those involving cortical thickness. Further
      evaluation of their influence on the surface and thickness of the cortical mantle
      is recommended. In addition, cortical volume appeared to be primarily dependent
      on surface and not thickness.

PMID- 25065712
TI  - Inferring the nature of anthropogenic threats from long-term abundance records.
AB  - Diagnosing the processes that threaten species persistence is critical for
      recovery planning and risk forecasting. Dominant threats are typically inferred
      by experts on the basis of a patchwork of informal methods. Transparent,
      quantitative diagnostic tools would contribute much-needed consistency,
      objectivity, and rigor to the process of diagnosing anthropogenic threats. Long
      term census records, available for an increasingly large and diverse set of taxa,
      may exhibit characteristic signatures of specific threatening processes and
      thereby provide information for threat diagnosis. We developed a flexible
      Bayesian framework for diagnosing threats on the basis of long-term census
      records and diverse ancillary sources of information. We tested this framework
      with simulated data from artificial populations subjected to varying degrees of
      exploitation and habitat loss and several real-world abundance time series for
      which threatening processes are relatively well understood: bluefin tuna (Thunnus
      maccoyii) and Atlantic cod (Gadus morhua) (exploitation) and Red Grouse (Lagopus
      lagopus scotica) and Eurasian Skylark (Alauda arvensis) (habitat loss). Our
      method correctly identified the process driving population decline for over 90%
      of time series simulated under moderate to severe threat scenarios. Successful
      identification of threats approached 100% for severe exploitation and habitat
      loss scenarios. Our method identified threats less successfully when threatening
      processes were weak and when populations were simultaneously affected by multiple
      threats. Our method selected the presumed true threat model for all real-world
      case studies, although results were somewhat ambiguous in the case of the
      Eurasian Skylark. In the latter case, incorporation of an ancillary source of
      information (records of land-use change) increased the weight assigned to the
      presumed true model from 70% to 92%, illustrating the value of the proposed
      framework in bringing diverse sources of information into a common rigorous
      framework. Ultimately, our framework may greatly assist conservation
      organizations in documenting threatening processes and planning species recovery.

PMID- 25065713
TI  - Repetitive oscillating atrial activation during supraventricular tachycardia.

PMID- 25065714
TI  - Roles of NMDA and dopamine D1 and D2 receptors in the acquisition and expression
      of flavor preferences conditioned by oral glucose in rats.
AB  - Animals learn to prefer flavors associated with the intake of sugar (sucrose,
      fructose, glucose) and fat (corn oil: CO) solutions. Conditioned flavor
      preferences (CFP) have been elicited for sugars based on orosensory (flavor
      flavor: e.g., fructose-CFP) and post-ingestive (flavor-nutrient: e.g.,
      intragastric (IG) glucose-CFP) processes. Dopamine (DA) D1, DA D2 and NMDA
      receptor antagonism differentially eliminate the acquisition and expression of
      fructose-CFP and IG glucose-CFP. However, pharmacological analysis of fat (CO)
      CFP, mediated by both flavor-flavor and flavor-nutrient processes, indicated that
      acquisition and expression of fat-CFP were minimally affected by systemic DA D1
      and D2 antagonists, and were reduced by NMDA antagonism. Therefore, the present
      study examined whether systemic DA D1 (SCH23390), DA D2 (raclopride) or NMDA (MK
      801) receptor antagonists altered acquisition and/or expression of CFP induced by
      oral glucose that should be mediated by both flavor-flavor and flavor-nutrient
      processes. Oral glucose-CFP was elicited following by training rats to drink one
      novel flavor (CS+, e.g., cherry) mixed in 8% glucose and another flavor (CS-,
      e.g., grape) mixed in 2% glucose. In expression studies, food-restricted rats
      drank these solutions in one-bottle sessions (2 h) over 10 days. Subsequent two
      bottle tests with the CS+ and CS- flavors mixed in 2% glucose occurred 0.5 h
      after systemic administration of vehicle (VEH), SCH23390 (50-800 nmol/kg),
      raclopride (50-800 nmol/kg) or MK-801 (50-200 MUg/kg). Rats displayed a robust
      CS+ preference following VEH treatment (94-95%) which was significantly though
      marginally attenuated by SCH23390 (67-70%), raclopride (77%) or MK-801 (70%) at
      doses that also markedly reduced overall CS intake. In separate acquisition
      studies, rats received VEH, SCH23390 (50-400 nmol/kg), raclopride (50-400
      nmol/kg) or MK-801 (100 MUg/kg) 0.5 h prior to ten 1-bottle training trials with
      CS+/8%G and CS-/2%G training solutions that was followed by six 2-bottle CS+ vs.
      CS- tests in 2% glucose conducted without injections. The significant and
      persistent CS+ preferences observed in the VEH (94-98%) group was significantly
      reduced by rats receiving SCH23390 at 400 nmol/kg (65-73%), raclopride at 200 or
      400 nmol/kg (76-82%) or MK-801 at 100 MUg/kg (68-69%). Thus, systemic DA D1 and
      DA D2 receptor antagonism produced smaller reductions in the expression of oral
      glucose-CFP relative to fructose-CFP or IG-glucose-CFP. Correspondingly, systemic
      DA D1, DA D2 and NMDA receptor antagonism also produced smaller reductions in the
      acquisition of oral glucose-CFP relative to fructose-CFP or IG-glucose-CFP. These
      data suggest, but do not prove, that the magnitude and persistence of these
      receptor antagonist effects upon sugar-CFP might depend upon the individual or
      combined engagement of flavor-flavor and flavor-nutrient processes.

PMID- 25065715
TI  - Effects of GnRH antagonist on endometrial protein profiles in the window of
      implantation.
AB  - GnRH antagonists can suppress luteinizing hormone and follicle-stimulating
      hormone (FSH), with less initial stimulatory effect and lower risk of ovarian
      hyperstimulation syndrome. The effects of GnRH antagonists on embryonic
      implantation remain controversial. To evaluate the effects of GnRH antagonists,
      endometrial tissues were biopsied from 12 women with intracytoplasmic sperm
      injection treatment, in which four subjects undergoing controlled ovulation
      stimulation with rFSH and GnRH antagonist, four subjects with a GnRH agonist long
      protocol, and four natural cycle controls. After iTRAQ quantification analysis,
      24 proteins showed differential expression between natural cycle and agonist
      treatment group and 39 proteins between natural cycle and antagonist treatment
      group. A total of seven proteins demonstrated differential expression only in
      antagonist treatment group. Bioinformatic analysis implied these proteins can
      function in cell processes including angiogenesis, cell proliferation, apoptosis,
      cell migration, and immune response. Furthermore, GnRH antagonist suppressed the
      function of GNAS and ANPEP, which were important for endometrial functions.
      Immunohistochemical staining showed that ANPEP was mainly localized in the human
      endometrial stroma, while ACO2, CDC5L, and GNAS were mainly localized in the
      glands. This study could provide insights into the effect of GnRH antagonists on
      the endometrium, and help optimize the embryo implantation and improve the
      success rate for GnRH antagonist protocol. 

PMID- 25065717
TI  - Molecular spectroscopic identification of the water compartments in bone.
AB  - Matrix bound water is a correlate of bone's fracture resistance and assessment of
      bound water is emerging as a novel measure of bone's mechanical integrity. Raman
      spectroscopy is one of the few nondestructive modalities to assess the hydration
      status in bone; however, it has not been used to study the OH-band in bone. A
      sequential dehydration protocol was developed to replace unbound (heat drying)
      and bound (ethanol or deuterium) water in bone. Raman spectra were collected
      serially to track the OH-band during dehydration. Spectra of synthetic
      hydroxyapatite, demineralized bone and bulk water were collected to identify
      mineral and collagen contributions to the OH-band. Band assignments were
      supported by computational simulations of the molecular vibrations of Gly-Pro-Hyp
      amino acid sequence. Experimentally and theoretically obtained spectra were
      interpreted for band-assignments. Water loss was measured gravimetrically and
      correlated to Raman intensities. Four peaks were identified to be sensitive to
      dehydration: 3220cm(-1) (water), 3325cm(-1) (NH and water), 3453cm(-1)
      (hydroxyproline and water), and 3584cm(-1) (mineral and water). These peaks were
      differentially sensitive to deuterium treatment such that some water peaks were
      replaced with deuterium oxide faster than the rest. Specifically, the peaks at
      3325 and 3584cm(-1) were more tightly bound to the matrix than the remaining
      bands. Comparison of dehydration in mineralized and demineralized bone revealed a
      volume of water that may be locked in the matrix by mineral crystals. The OH
      range of bone was dominated by collagen and the water since the spectral profile
      of dehydrated demineralized bone was similar to that of the mineralized bone.
      Furthermore, water associates to bone mainly by collagen as findings of
      experimentally and theoretically spectra. The current work is among the first
      thorough analysis of the Raman OH stretch band in bone and such spectral
      information may be used to understand the involvement of water in the fragility
      of aging and in diseased bone. 

PMID- 25065716
TI  - The condensin complexes play distinct roles to ensure normal chromosome
      morphogenesis during meiotic division in Arabidopsis.
AB  - Meiosis is a specialized cell division essential for sexual reproduction. During
      meiosis the chromosomes are highly organized, and correct chromosome architecture
      is required for faithful segregation of chromosomes at anaphase I and II.
      Condensin is involved in chromosome organization during meiotic and mitotic cell
      divisions. Three condensin subunits, AtSMC4 and the condensin I and II specific
      subunits AtCAP-D2 and AtCAP-D3, respectively, have been studied for their role in
      meiosis. This has revealed that both the condensin I and condensin II complexes
      are required to maintain normal structural integrity of the meiotic chromosomes
      during the two nuclear divisions. Their roles appear functionally distinct in
      that condensin I is required to maintain normal compaction of the centromeric
      repeats and 45S rDNA, whereas loss of condensin II was associated with extensive
      interchromosome connections at metaphase I. Depletion of condensin is also
      associated with a slight reduction in crossover formation, suggesting a role
      during meiotic prophase I. 

PMID- 25065718
TI  - Intact IL-12 signaling is necessary for the generation of human natural killer
      cells with enhanced effector function after restimulation.

PMID- 25065719
TI  - Causes of epidermal filaggrin reduction and their role in the pathogenesis of
      atopic dermatitis.
AB  - The epidermis protects human subjects from exogenous stressors and helps to
      maintain internal fluid and electrolyte homeostasis. Filaggrin is a crucial
      epidermal protein that is important for the formation of the corneocyte, as well
      as the generation of its intracellular metabolites, which contribute to stratum
      corneum hydration and pH. The levels of filaggrin and its degradation products
      are influenced not only by the filaggrin genotype but also by inflammation and
      exogenous stressors. Pertinently, filaggrin deficiency is observed in patients
      with atopic dermatitis regardless of filaggrin mutation status, suggesting that
      the absence of filaggrin is a key factor in the pathogenesis of this skin
      condition. In this article we review the various causes of low filaggrin levels,
      centralizing the functional and morphologic role of a deficiency in filaggrin,
      its metabolites, or both in the etiopathogenesis of atopic dermatitis. 

PMID- 25065720
TI  - Enhanced CD46-induced regulatory T cells suppress allergic inflammation after
      Dermatophagoides pteronyssinus-specific immunotherapy.

PMID- 25065722
TI  - Reply: To PMID 24766873.

PMID- 25065721
TI  - Basophil activation test discriminates between allergy and tolerance in peanut
      sensitized children.
AB  - BACKGROUND: Most of the peanut-sensitized children do not have clinical peanut
      allergy. In equivocal cases, oral food challenges (OFCs) are required. However,
      OFCs are laborious and not without risk; thus, a test that could accurately
      diagnose peanut allergy and reduce the need for OFCs is desirable. OBJECTIVE: To
      assess the performance of basophil activation test (BAT) as a diagnostic marker
      for peanut allergy. METHODS: Peanut-allergic (n = 43), peanut-sensitized but
      tolerant (n = 36) and non-peanut-sensitized nonallergic (n = 25) children
      underwent skin prick test (SPT) and specific IgE (sIgE) to peanut and its
      components. BAT was performed using flow cytometry, and its diagnostic
      performance was evaluated in relation to allergy versus tolerance to peanut and
      validated in an independent population (n = 65). RESULTS: BAT in peanut-allergic
      children showed a peanut dose-dependent upregulation of CD63 and CD203c while
      there was no significant response to peanut in peanut-sensitized but tolerant (P
      < .001) and non-peanut-sensitized nonallergic children (P < .001). BAT optimal
      diagnostic cutoffs showed 97% accuracy, 95% positive predictive value, and 98%
      negative predictive value. BAT allowed reducing the number of required OFCs by
      two-thirds. BAT proved particularly useful in cases in which specialists could
      not accurately diagnose peanut allergy with SPT and sIgE to peanut and to Arah2.
      Using a 2-step diagnostic approach in which BAT was performed only after
      equivocal SPT or Arah2-sIgE, BAT had a major effect (97% reduction) on the number
      of OFCs required. CONCLUSIONS: BAT proved to be superior to other diagnostic
      tests in discriminating between peanut allergy and tolerance, particularly in
      difficult cases, and reduced the need for OFCs.

PMID- 25065723
TI  - Loss of allergenic proteins during boiling explains tolerance to boiled peanut in
      peanut allergy.

PMID- 25065724
TI  - Effect of antioxidants and nutrients in patients with allergy and asthma.

PMID- 25065725
TI  - A study of a three-dimensional PLGA sponge containing natural polymers co
      cultured with endothelial and mesenchymal stem cells as a tissue engineering
      scaffold.
AB  - The interaction between vascular endothelial cells (ECs) and vascular smooth
      muscle cells (VSMCs) in a complex hemodynamic and mechanical environment plays an
      important role in the control of blood vessel growth and function. Despite the
      importance of VSMCs, substitutes are needed for vascular therapies. A potential
      VSMC substitute is human adult bone marrow derived mesenchymal stem cells
      (hMSCs). In this study, the effect of poly(lactic-co-glycolic acid) (PLGA)
      scaffolds containing three natural polymers (demineralized bone particles, silk,
      and small intestine submucosa) on the phenotype of MSCs and SMCs cultured with or
      without ECs was investigated. The study objective was to create a media
      equivalent for a tissue engineered blood vessel using PLGA, natural polymers, and
      MSCs co-cultured with ECs. The PLGA containing the natural polymers silk and SIS
      showed increased proliferation and cell adhesion. The presence of silk and DBP
      promoted a MSC phenotype change into a SMC-like phenotype at the mRNA level;
      however these differences at the protein level were not seen. Additionally, PLGA
      containing SIS did not induce SMC gene or protein upregulation. Finally, the
      effect of ECs in combination with the natural polymers was tested. When co
      cultured with ECs, the mRNA of SMC specific markers in MSCs and SMCs were
      increased when compared to SMCs or MSCs alone. However, MSCs, when co-cultured
      with ECs on PLGA containing silk, exhibited significantly increased alpha-SMA and
      calponin expression when compared to PLGA only scaffolds. These results indicate
      that the natural polymer silk in combination with the co-culture of endothelial
      cells was most effective at increasing cell viability and inducing a SMC-like
      phenotype at the mRNA and protein level in MSCs. 

PMID- 25065726
TI  - Cole disease: a case report and literature review.

PMID- 25065728
TI  - Bioinjection treatment: effects of post-injection residual stress on left
      ventricular wall stress.
AB  - Injection of biomaterials into diseased myocardium has been associated with
      decreased myofiber stress, restored left ventricular (LV) geometry and improved
      LV function. However, its exact mechanism(s) of action remained unclear. In this
      work, we present the first patient-specific computational model of biomaterial
      injection that accounts for the possibility of residual strain and stress
      introduced by this treatment. We show that the presence of residual stress can
      create more heterogeneous regional myofiber stress and strain fields. Our
      simulation results show that the treatment generates low stress and stretch areas
      between injection sites, and high stress and stretch areas between the injections
      and both the endocardium and epicardium. Globally, these local changes are
      translated into an increase in average myofiber stress and its standard deviation
      (from 6.9 +/- 4.6 to 11.2 +/- 48.8 kPa and 30 +/- 15 to 35.1 +/- 50.9 kPa at end
      diastole and end-systole, respectively). We also show that the myofiber stress
      field is sensitive to the void-to-size ratio. For a constant void size, the
      myofiber stress field became less heterogeneous with decreasing injection volume.
      These results suggest that the residual stress and strain possibly generated by
      biomaterial injection treatment can have large effects on the regional myocardial
      stress and strain fields, which may be important in the remodeling process.

PMID- 25065727
TI  - A rare variant association test based on combinations of single-variant tests.
AB  - Next generation sequencing technologies make direct testing rare variant
      associations possible. However, the development of powerful statistical methods
      for rare variant association studies is still underway. Most of existing methods
      are burden and quadratic tests. Recent studies show that the performance of each
      of burden and quadratic tests depends strongly upon the underlying assumption and
      no test demonstrates consistently acceptable power. Thus, combined tests by
      combining information from the burden and quadratic tests have been proposed
      recently. However, results from recent studies (including this study) show that
      there exist tests that can outperform both burden and quadratic tests. In this
      article, we propose three classes of tests that include tests outperforming both
      burden and quadratic tests. Then, we propose the optimal combination of single
      variant tests (OCST) by combining information from tests of the three classes. We
      use extensive simulation studies to compare the performance of OCST with that of
      burden, quadratic and optimal single-variant tests. Our results show that OCST
      either is the most powerful test or has similar power with the most powerful
      test. We also compare the performance of OCST with that of the two existing
      combined tests. Our results show that OCST has better power than the two combined
      tests. 

PMID- 25065729
TI  - Elevation and orientation of external loads influence trunk neuromuscular
      response and spinal forces despite identical moments at the L5-S1 level.
AB  - A wide range of loading conditions involving external forces with varying
      magnitudes, orientations and locations are encountered in daily activities. Here
      we computed the effect on trunk biomechanics of changes in force location (two
      levels) and orientation (5 values) in 4 subjects in upright standing while
      maintaining identical external moment of 15 Nm, 30 Nm or 45 Nm at the L5-S1.
      Driven by measured kinematics and gravity/external loads, the finite element
      models yielded substantially different trunk neuromuscular response with moderate
      alterations (up to 24% under 45 Nm moment) in spinal loads as the load
      orientation varied. Under identical moments, compression and shear forces at the
      L5-S1 as well as forces in extensor thoracic muscles progressively decreased as
      orientation of external forces varied from downward gravity (90 degrees ) all the
      way to upward (-25 degrees ) orientation. In contrast, forces in local lumbar
      muscles followed reverse trends. Under larger horizontal forces at a lower
      elevation, lumbar muscles were much more active whereas extensor thoracic muscle
      forces were greater under smaller forces at a higher elevation. Despite such
      differences in activity pattern, the spinal forces remained nearly identical (<6%
      under 45 Nm moment). The published recorded surface EMG data of extensor muscles
      trend-wise agreed with computed local muscle forces as horizontal load elevation
      varied but were overall different from results in both local and global muscles
      when load orientation altered. Predictions demonstrate the marked effect of
      external force orientation and elevation on the trunk neuromuscular response and
      spinal forces and questions attempts to estimate spinal loads based only on
      consideration of moments at a spinal level.

PMID- 25065730
TI  - Contribution of the skin, rectus abdominis and their sheaths to the structural
      response of the abdominal wall ex vivo.
AB  - A better understanding of the abdominal wall biomechanics could help designing
      new treatments for incisional hernia. In the current study, an experimental
      protocol was developed to evaluate the contributions of the abdominal wall
      components to the structural response of the anterior part of the abdominal wall.
      The specimens underwent 3 dissections (removal of (1) skin and subcutaneous fat,
      (2) anterior rectus sheath, (3) rectus abdominis muscles). After each dissection,
      they were subjected to air pressure up to 3 kPa. Ultrasound images and associated
      elastographic maps were collected at 0, 2 and 3 kPa in the intact state and
      strains on the internal surface were calculated using stereo-correlation in all
      states. Strains on the rectus abdominis and linea alba were analyzed. After the
      dissection of the anterior sheath of the rectus abdominis, longitudinal strain
      was found significantly different on the linea alba (5% at 3 kPa) and on the
      rectus abdominis area (11% at 3 kPa). The current results highlight the
      importance of the rectus sheath in the structural response of the anterior part
      of the abdominal wall ex vivo. Geometrical characteristics such as thicknesses
      and radii of curvature and mechanical properties (shear modulus of the rectus
      abdominis, e.g. at 0 pressure the average value is 14 kPa) were provided in order
      to facilitate future modeling efforts.

PMID- 25065731
TI  - Fatigue microcracks that initiate fracture are located near elevated
      intracortical porosity but not elevated mineralization.
AB  - In vivo microcracks in cortical bone are typically observed within more highly
      mineralized interstitial tissue, but postmortem investigations are inherently
      limited to cracks that did not lead to fracture which may be misleading with
      respect to understanding fracture mechanisms. We hypothesized that the one
      fatigue microcrack which initiates fracture is located spatially adjacent to
      elevated intracortical porosity but not elevated mineralization. Therefore, the
      spatial correlation between intracortical porosity, elevated mineralization, and
      fatigue microdamage was investigated by combining, for the first time,
      sequential, nondestructive, three-dimensional micro-computed tomography (micro
      CT) measurements of each in cortical bone specimens subjected to compressive
      fatigue loading followed by a tensile overload to fracture. Fatigue loading
      resulted in significant microdamage accumulation and compromised mechanical
      properties upon tensile overload compared to control specimens. The microdamage
      that initiated fracture upon tensile overload was able to be identified in all
      fatigue-loaded specimens using contrast-enhanced micro-CT and registered images.
      Two-point (or pair) correlation functions revealed a spatial correlation between
      microdamage at the fracture initiation site and intracortical porosity, but not
      highly mineralized tissue, confirming the hypothesis. This difference was unique
      to the fracture initiation site. Intracortical porosity and highly mineralized
      tissue exhibited a significantly lower and higher probability, respectively, of
      being located spatially adjacent to all sites of microdamage compared to the
      fracture initiation site. Therefore, the results of this study suggest that human
      cortical bone is tolerant of most microcracks, which are generally
      compartmentalized within the more highly mineralized interstitial tissue, but a
      single microcrack of sufficient size located in spatial proximity to
      intracortical porosity can compromise fracture resistance. 

PMID- 25065732
TI  - Reduced brain reward response during cooperation in first-degree relatives of
      patients with psychosis: an fMRI study.
AB  - BACKGROUND: Psychosis is characterized by a profound lack of trust and disturbed
      social interactions. Investigating the neural basis of these deficits is
      difficult because of medication effects but first-degree relatives show
      qualitatively similar abnormalities to patients with psychosis on various tasks.
      This study aimed to investigate neural activation in siblings of patients in
      response to an interactive task. We hypothesized that, compared to controls,
      siblings would show (i) less basic trust at the beginning of the task and (ii)
      reduced activation of the brain reward and mentalizing systems. METHOD:
      Functional magnetic resonance imaging (fMRI) data were acquired on 50 healthy
      siblings of patients with psychosis and 33 healthy controls during a multi-round
      trust game with a cooperative counterpart. An a priori region-of-interest (ROI)
      analysis of the caudate, temporoparietal junction (TPJ), superior temporal sulcus
      (STS), insula and medial prefrontal cortex (mPFC) was performed focusing on the
      investment and repayment phases. An exploratory whole-brain analysis was run to
      test for group-wise differences outside these ROIs. RESULTS: The siblings'
      behaviour during the trust game did not differ significantly from that of the
      controls. At the neural level, siblings showed reduced activation of the right
      caudate during investments, and the left insula during repayments. In addition,
      the whole-brain analysis revealed reduced putamen activation in siblings during
      investments. CONCLUSIONS: The findings suggest that siblings show aberrant
      functioning of regions traditionally involved in reward processing in response to
      cooperation, which may be associated with the social reward deficits observed in
      psychosis.

PMID- 25065733
TI  - HPV-positive oropharyngeal squamous cell carcinoma is associated with TIMP3 and
      CADM1 promoter hypermethylation.
AB  - Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human
      papillomavirus (HPV) in a proportion of tumors. HPV-positive OPSCC is considered
      a distinct molecular entity with a prognostic advantage compared to HPV-negative
      cases. Silencing of cancer-related genes by DNA promoter hypermethylation may
      play an important role in the development of OPSCC. Hence, we examined promoter
      methylation status in 24 common tumor suppressor genes in a group of 200 OPSCCs
      to determine differentially methylated genes in HPV-positive versus HPV-negative
      primary OPSCC. Methylation status was correlated with HPV status, clinical
      features, and patient survival using multivariate methods. Additionally,
      methylation status of 16 cervical squamous cell carcinomas (SCC) was compared
      with HPV-positive OPSCC. Using methylation-specific probe amplification, HPV
      positive OPSCC showed a significantly higher cumulative methylation index (CMI)
      compared to HPV-negative OPSCC (P=0.008). For the genes CDH13, DAPK1, and RARB,
      both HPV-positive and HPV-negative OPSCC showed promoter hypermethylation in at
      least 20% of the tumors. HPV status was found to be an independent predictor of
      promoter hypermethylation of CADM1 (P < 0.001), CHFR (P = 0.027), and TIMP3 (P <
      0.001). CADM1 and CHFR showed similar methylation patterns in OPSCC and cervical
      SCC, but TIMP3 showed no methylation in cervical SCC in contrast to OPSCC.
      Methylation status of neither individual gene nor CMI was associated with
      survival. These results suggest that HPV-positive tumors are to a greater extent
      driven by promotor hypermethylation in these tumor suppressor genes. Especially
      CADM1 and TIMP3 are significantly more frequently hypermethylated in HPV-positive
      OPSCC and CHFR in HPV-negative tumors. 

PMID- 25065735
TI  - Patient-specific versus conventional instrumentation for total knee arthroplasty:
      peri-operative and cost differences.
AB  - The role of patient-specific instrumentation in total knee arthroplasty (TKA) is
      yet to be clearly defined. Current evidence evaluating peri-operative and cost
      differences against conventional TKA is unclear. We reviewed 356 TKAs between
      July 2008 and April 2013; 306 TKAs used patient-specific instrumentation while 50
      had conventional instrumentation. The patient-specific instrumentation cohort
      averaged 20.4 min less surgical time (P < 0.01) and had a 42% decrease in
      operating room turnover time (P = 0.022). At our institution, the money saved
      through increased operating room efficiency offset the cost of the custom cutting
      blocks and pre-operative advanced imaging. Routine use of patient-specific TKA
      can be performed with less surgical time, no increase in peri-operative
      morbidity, and at no increased cost when compared to conventional TKA. 

PMID- 25065734
TI  - Class-IIa Histone Deacetylase Inhibition Promotes the Growth of Neural Processes
      and Protects Them Against Neurotoxic Insult.
AB  - Small molecule histone deacetylase inhibitors (HDIs) hold much promise as
      pharmacological modifiers of the epigenetic status of the central nervous system
      (CNS), given their ability to cross the blood-brain barrier. This is particularly
      relevant given the lack of disease-modifying therapies for many neurodegenerative
      diseases and that epigenetic perturbations are increasingly recognised as playing
      a key role in their pathophysiology. In particular, emerging evidence in recent
      years has shown that epigenetic dysregulation may contribute to dopaminergic
      neuronal death in Parkinson's disease. As a result, a number of pan-HDIs have
      been explored as potential neuroprotective agents for dopaminergic neurons.
      However, it is not known if the neuroprotective effects of pan-histone
      deacetylase (HDAC) inhibition are a general phenomenon or if these effects
      require inhibition of specific classes of HDACs. Here, we examine the ability of
      class-specific HDIs to promote neurite growth in a variety of cellular contexts.
      We find that MC1568, a class IIa-specific HDI, promotes neurite growth and
      arbourisation and protects neurite arbours against neurotoxic insult.
      Furthermore, we show that class IIa-specific HDAC inhibition results in
      activation of the canonical Smad signalling pathway, which is known to promote
      the survival and growth of midbrain dopaminergic neurons. These results
      demonstrate the potential of class IIa-specific HDIs as regulators of neuronal
      structure and suggest they should be examined in animal models of Parkinson's
      disease as the next stage in rationalising their use as a potential therapy for
      this disorder. 

PMID- 25065736
TI  - Enantioselective total syntheses of cyathane diterpenoids.
AB  - A Personal Account describing the enantioselective total syntheses of cyathane
      diterpenoids achieved in the Nakada group. A convergent approach to the cyathane
      scaffold, the [5-6-7] tricyclic carbon skeleton commonly found in cyathane
      diterpenoids, has been developed using the catalytic asymmetric intramolecular
      cyclopropanation (CAIMCP) and baker's yeast reduction. This approach has been
      successfully applied for the enantioselective total syntheses of (+)-allocyathin
      B2 , (-)-erinacine B, and (-)-erinacine E. The total synthesis of (-)-erinacine E
      has been achieved via the acyl group migratory intramolecular aldol reaction,
      which prevents the retro-aldol reaction and allows the construction of the
      strained structure. The highly efficient and stereoselective total syntheses of (
      )-scabronines G, A, D, and (-)-episcabronine A have been achieved via the
      oxidative dearomatization/inverse electron demand Diels-Alder reaction cascade.
      Cascade reactions comprising three and five consecutive reactions were employed
      for the highly efficient total syntheses of (-)-scabronine A and (-)
      episcabronine A, respectively. 

PMID- 25065738
TI  - Measurement of cell adhesion force by vertical forcible detachment using an
      arrowhead nanoneedle and atomic force microscopy.
AB  - The properties of substrates and extracellular matrices (ECM) are important
      factors governing the functions and fates of mammalian adherent cells. For
      example, substrate stiffness often affects cell differentiation. At focal
      adhesions, clustered-integrin bindings link cells mechanically to the ECM. In
      order to quantitate the affinity between cell and substrate, the cell adhesion
      force must be measured for single cells. In this study, forcible detachment of a
      single cell in the vertical direction using AFM was carried out, allowing
      breakage of the integrin-substrate bindings. An AFM tip was fabricated into an
      arrowhead shape to detach the cell from the substrate. Peak force observed in the
      recorded force curve during probe retraction was defined as the adhesion force,
      and was analyzed for various types of cells. Some of the cell types adhered so
      strongly that they could not be picked up because of plasma membrane breakage by
      the arrowhead probe. To address this problem, a technique to reinforce the
      cellular membrane with layer-by-layer nanofilms composed of fibronectin and
      gelatin helped to improve insertion efficiency and to prevent cell membrane
      rupture during the detachment process, allowing successful detachment of the
      cells. This method for detaching cells, involving cellular membrane
      reinforcement, may be beneficial for evaluating true cell adhesion forces in
      various cell types. 

PMID- 25065737
TI  - Nanomechanical biomarkers of single circulating tumor cells for detection of
      castration resistant prostate cancer.
AB  - BACKGROUND: Emerging evidence shows that nanomechanical phenotypes of circulating
      tumor cells (CTC) could become potential biomarkers for metastatic castration
      resistant prostate cancer (mCRPC). METHODS: To determine the nanomechanical
      phenotypes of CTCs we applied atomic force microscopy (AFM) employing the
      PeakForce quantitative nanomechanical (QNM) imaging. We assessed biophysical
      parameters (elasticity, deformation, and adhesion) of 130 CTCs isolated from
      blood samples from five castration sensitive (CS) and 12 castration resistant
      prostate cancer (CRPCa) patients. RESULTS: We found that CTCs from CRPCa patients
      are three times softer, three times more deformable, and seven times more
      adhesive than counterparts from CSPCa patients. Both nonsupervised hierarchical
      clustering and principle component analysis show that three combined
      nanomechanical parameters could constitute a valuable set to distinguish between
      CSPCa and CRPCa. CONCLUSIONS: [corrected] Our study indicates that nanomechanical
      phenotypes of CTCs may serve as novel and effective biomarkers for mCRPC.

PMID- 25065739
TI  - Crystal structures of type IIIH NAD-dependent D-3-phosphoglycerate dehydrogenase
      from two thermophiles.
AB  - In the L-Serine biosynthesis, D-3-phosphoglycerate dehydrogenase (PGDH) catalyzes
      the inter-conversion of D-3-phosphoglycerate to phosphohydroxypyruvate. PGDH
      belongs to 2-hydroxyacid dehydrogenases family. We have determined the crystal
      structures of PGDH from Sulfolobus tokodaii (StPGDH) and Pyrococcus horikoshii
      (PhPGDH) using X-ray diffraction to resolution of 1.77A and 1.95A, respectively.
      The PGDH protomer from both species exhibits identical structures, consisting of
      substrate binding domain and nucleotide binding domain. The residues and water
      molecules interacting with the NAD are identified. The catalytic triad residues
      Glu-His-Arg are highly conserved. The residues involved in the dimer interface
      and the structural features responsible for thermostability are evaluated.
      Overall, structures of PGDHs with two domains and histidine at the active site
      are categorized as type IIIH and such PGDHs structures having this type are
      reported for the first time.

PMID- 25065740
TI  - The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung
      cancer.
AB  - PHF8 is a JmjC domain-containing protein and erases repressive histone marks
      including H4K20me1 and H3K9me1/2. It binds to H3K4me3, an active histone mark
      usually located at transcription start sites (TSSs), through its plant homeo
      domain, and is thus recruited and enriched in gene promoters. PHF8 is involved in
      the development of several types of cancer, including leukemia, prostate cancer,
      and esophageal squamous cell carcinoma. Herein we report that PHF8 is an
      oncogenic protein in human non-small cell lung cancer (NSCLC). PHF8 is up
      regulated in human NSCLC tissues, and high PHF8 expression predicts poor
      survival. Our in vitro and in vivo evidence demonstrate that PHF8 regulates lung
      cancer cell proliferation and cellular transformation. We found that PHF8
      knockdown induces DNA damage and apoptosis in lung cancer cells. PHF8 promotes
      miR-21 expression in human lung cancer, and miR-21 knockdown blocks the effects
      of PHF8 on proliferation and apoptosis of lung cancer cells. In summary, PHF8
      promotes lung cancer cell growth and survival by regulating miR-21. 

PMID- 25065741
TI  - Baicalin prevents Candida albicans infections via increasing its apoptosis rate.
AB  - BACKGROUND: These experiments were employed to explore the mechanisms underlying
      baicalin action on Candida albicans. METHODOLOGY AND PRINCIPAL FINDINGS: We
      detected the baicalin inhibition effects on three isotope-labeled precursors of
      (3)H-UdR, (3)H-TdR and (3)H-leucine incorporation into C. albicans using the
      isotope incorporation technology. The activities of Succinate Dehydrogenase
      (SDH), cytochrome oxidase (CCO) and Ca(2)(+)-Mg(2+) ATPase, cytosolic Ca(2+)
      concentration, the cell cycle and apoptosis, as well as the ultrastructure of
      C.albicans were also tested. We found that baicalin inhibited (3)H-UdR, (3)H-TdR
      and (3)H-leucine incorporation into C.albicans (P<0.005). The activities of the
      SDH and Ca(2)(+)-Mg(2+) ATPase of C.albicans in baicalin groups were lower than
      those in control group (P<0.05). Ca(2+) concentrations of C. albicans in baicalin
      groups were much higher than those in control group (P<0.05). The ratio of
      C.albicans at the G0/G1 stage increased in baicalin groups in dose dependent
      manner (P<0.01). There were a significant differences in the apoptosis rate of
      C.albicans between baicalin and control groups (P<0.01). After 12-48 h incubation
      with baicalin (1mg/ml), C. albicans shown to be markedly damaged under
      transmission electron micrographs. INNOVATION AND SIGNIFICANCE: Baicalin can
      increase the apoptosis rate of C. albicans. These effects of Baicalin may
      involved in its inhibiting the activities of the SDH and Ca(2)(+)-Mg(2+) ATPase,
      increasing cytosolic Ca(2+) content and damaging the ultrastructure of C.
      albicans.

PMID- 25065742
TI  - Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial
      dysfunction observed in mitochondrial disease.
AB  - Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive
      oxygen species (ROS) are generated during aerobic respiration in mitochondria,
      mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is
      caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial
      tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease.
      Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has
      been assessed. Then, cybrid cells, which are constructed by the fusion of an
      enucleated cell harboring altered mtDNA with a rho(0) cell, have long been used
      for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new
      method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease.
      The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was
      successfully translocated to the mitochondrial matrix. Additionally, mt tRNA
      cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity,
      was observed. 

PMID- 25065743
TI  - WTIP interacts with ASXL2 and blocks ASXL2-mediated activation of retinoic acid
      signaling.
AB  - The Asx-like (ASXL) family proteins are chromatin factors that play dual roles in
      transcriptional activation and repression. ASXL2 is highly expressed in the heart
      and is required for proper heart development and function. Here, we identify a
      novel ASXL2-binding partner, the LIM domain-containing protein WTIP. Genetic and
      biochemical assays show a direct interaction between ASXL2 and WTIP. In HeLa
      cells, ASXL2 enhances retinoic acid-dependent luciferase activity, while WTIP
      represses it. Furthermore, WTIP blocks ASXL2's stimulatory effect on
      transcription. In addition, we found that ASXL2 and WTIP are expressed in mouse
      embryonic epicardial cells, a tissue that is regulated by retinoic acid
      signaling. Together, these results implicate ASXL2 and WTIP in regulation of
      retinoic acid signaling during heart development. 

PMID- 25065744
TI  - Baicalin reverse AMPA receptor expression and neuron apoptosis in chronic
      unpredictable mild stress rats.
AB  - Changes of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      expression could impacts the viability of neurons and brain levels of brain
      derived neurotrophic factor (BDNF) expression in the key brain structures in the
      pathophysiology of depressive disorder. In the present study, chronic
      unpredictable mild stress (CUMS) degraded performance decreased AMPA receptor
      expression and increased neuron apoptosis. Treatment with baicalin (20, 40mg/kg)
      significantly reversed these changes. This study demonstrates that baicalin has
      potent antidepressant effect, likely through up-regulated the expression of AMPA
      receptor and suppression neuron apoptosis in CUMS-treated rats. 

PMID- 25065745
TI  - Profound and rapid reduction in body temperature induced by the melanocortin
      receptor agonists.
AB  - The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation
      and its agonist MTII has been widely used to study the role of MC4Rs in energy
      expenditure promotion and feeding reduction. Unexpectedly, we observed that
      intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both
      body temperature and energy expenditure, which was independent of its effect on
      feeding and followed by a prolonged increase in energy expenditure. The rapid
      reduction was at least partly mediated by brain neurons since
      intracerebroventricular (icv) administration of alpha melanocyte-stimulating
      hormone, an endogenous melanocortin receptor agonist, produced a similar
      response. In addition, the body temperature-lowering effect of MTII was
      independent of the presence of MC4Rs, but in a similar fashion to the previously
      shown effect on body temperature by 5'AMP. Moreover, beta-adrenergic receptors
      (beta-ARs) were required for the recovery from low body temperature induced by
      MTII and further pharmacological studies showed that the MTII's effect on body
      temperature may be partially mediated by the vasopressin V1a receptors.
      Collectively, our results reveal a previously unappreciated role for the
      melanocortin pathway in rapidly lowering body temperature. 

PMID- 25065746
TI  - The glyceraldehyde 3-phosphate dehydrogenase gene (GAPDH) is regulated by myeloid
      zinc finger 1 (MZF-1) and is induced by calcitriol.
AB  - Recently, new tissue-specific functions for glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) have been discovered, aside from its archetypal function in
      glycolysis. This casts doubt on the legitimacy of using GAPDH as a normalization
      control for gene expression analysis. We report the binding of the myeloid zinc
      finger-1 (MZF-1) transcription factor to the human GAPDH promoter. Furthermore,
      we show that up-regulation of MZF-1 by 1,25-dihydroxyvitamin D3 (calcitriol)
      induces GAPDH in HS-5 stromal fibroblasts, while knockdown of MZF1 by shRNA leads
      to a concomitant reduction in GAPDH expression. This argues that MZF-1 regulates
      GAPDH, indicating a role for GAPDH in calcitriol-mediated signaling. 

PMID- 25065747
TI  - Activation of the central histaminergic system mediates arachidonic-acid-induced
      cardiovascular effects.
AB  - The aim of this study was to explain the involvement of the central histaminergic
      system in arachidonic acid (AA)-induced cardiovascular effects in normotensive
      rats using hemodynamic, immunohistochemistry, and microdialysis studies.
      Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 MUmol)
      induced dose- and time-dependent increases in mean arterial pressure and
      decreased heart rate in conscious normotensive Sprague-Dawley rats. Central
      injection of AA (0.5 MUmol) also increased posterior hypothalamic extracellular
      histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the
      posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1
      immunoreactivity in the posterior hypothalamus induced by AA (0.5 MUmol; i.c.v.)
      were almost completely blocked by the H2 receptor antagonist ranitidine (50 and
      100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker
      chlorpheniramine (100 nmol; i.c.v.) and the H3-H4 receptor antagonist
      thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate
      that centrally administered AA induces pressor and bradycardic responses in
      conscious rats. Moreover, we suggest that AA may activate histaminergic neurons
      and increase extracellular histamine levels, particularly in the posterior
      hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in
      AA-induced cardiovascular effects under normotensive conditions. 

PMID- 25065748
TI  - Acute arsenic treatment alters arachidonic acid and its associated metabolite
      levels in the brain of C57Bl/6 mice.
AB  - The toxic effects of arsenic on the whole brain, as well as the discrete regions,
      has been previously reported for mice. We investigated the effects of acute
      arsenite (As(III)) on brain levels of arachidonic acid (AA) and its associated
      metabolites generated through cytochrome P450 (CYP), cyclooxygenase (COX), and
      lipoxygenase (LOX) pathways. Our results demonstrated that acute As(III)
      treatment (12.5 mg.(kg body mass)(-1)) decreases cytosolic phospholipase A2
      (cPLA2) with a subsequent decrease in its catalytic activity and brain AA levels.
      In addition, As(III) differentially altered CYP epoxygenases and CYP omega
      hydroxylases, but it did not affect brain Ephx2 mRNA or sEH catalytic activity
      levels. As(III)-mediated effects on Cyps caused an increase in brain 5,6
      epoxyeicosatrienoic acid (5,6-EET) and 16/17-hydroxyeicosatetreinoic acid (16/17
      HETE) levels, and a decrease in 18- and 20-HETE levels. Furthermore, As(III)
      increased cyclooxygenase-2 (COX-2) mRNA while decreasing prostaglandins F2alpha
      (PGF2alpha) and PGJ2. As(III) also increased brain 5-lipoxygenase (5-LOX) and 15
      LOX mRNA, but decreased 12-LOX mRNA. These changes in LOX mRNA were associated
      with a decrease in 8/12-HETE levels only. In conclusion, this is the first
      demonstration that As(III) decreases AA levels coinciding with alterations to
      EET, HETE, and PG levels, which affects brain development and neurochemistry. 

PMID- 25065749
TI  - Bridges in translational medicine: a case for metabolism, inflammation, and
      nutrition.

PMID- 25065750
TI  - Antagonistic roles for H3K36me3 and H3K27me3 in the cold-induced epigenetic
      switch at Arabidopsis FLC.
AB  - Posttranslational modifications of histone tails are an important factor
      regulating chromatin structure and gene expression. Epigenetic memory systems
      have been predicted to involve mutually exclusive histone modifications that,
      through positive feedback mechanisms, generate bistable states. How the states
      are interconverted is not understood, and whether the histone modifications are
      sufficient for epigenetic memory is still greatly debated. We have exploited the
      process of vernalization, the slow quantitative epigenetic silencing of
      Arabidopsis FLC induced by cold, to detail with fine temporal and spatial
      resolution the dynamics of histone modifications during an epigenetic switch. The
      profiles of H3K36me3, H3K4me3, and H3K4me2 at FLC throughout the vernalization
      process were compared to H3K27me3, which accumulates at a local nucleation region
      during the cold and spreads across the locus on return to the warm. We find for
      many phases of the vernalization process that H3K36me3 and H3K27me3 show opposing
      profiles in the FLC nucleation region and gene body, that H3K36me3 and H3K27me3
      rarely coexist on the same histone tail, and that this antagonism is functionally
      important. A lack of H3K36me3 results in a fully silenced state at FLC even in
      the absence of cold. We therefore propose that H3K36me3 is the opposing
      modification to H3K27me3 in the Polycomb-mediated silencing of FLC. However, the
      lack of an absolute mirror profile predicted from modeling suggests that their
      antagonistic roles contribute a necessary, but not sufficient, component of the
      mechanism enabling switching between and inheritance of epigenetic states.

PMID- 25065751
TI  - Monkeys spontaneously discriminate their unfamiliar paternal kin under natural
      conditions using facial cues.
AB  - Kin recognition can enhance inclusive fitness via nepotism and optimal
      outbreeding. Mechanisms allowing recognition of patrilineal relatives are of
      particular interest in species in which females mate promiscuously, leading to
      paternity uncertainty. Humans are known to detect facial similarities between kin
      in the faces of third parties, and there is some evidence for continuity of this
      ability in nonhuman primates . However, no study has yet shown that this
      propensity translates into an ability to detect one's own relatives, one of the
      key prerequisites for gaining fitness benefits. Here we report a field experiment
      demonstrating that free-ranging rhesus macaques (Macaca mulatta) spontaneously
      discriminate between facial images of their paternal half-siblings and unrelated
      individuals, when both animals are unfamiliar to the tested individual.
      Specifically, subjects systematically biased their inspection time toward nonkin
      when the animals pictured were of their own sex (potential threats), relative to
      when they were of the opposite sex (potential mates). Our results provide strong
      evidence for visual phenotype matching and the first demonstration in any primate
      that individuals can spontaneously detect their own paternal relatives on the
      basis of facial cues under natural conditions.

PMID- 25065752
TI  - Phylogenomic resolution of the class Ophiuroidea unlocks a global microfossil
      record.
AB  - Our understanding of the origin, evolution, and biogeography of seafloor fauna is
      limited because we have insufficient spatial and temporal data to resolve
      underlying processes. The abundance and wide distribution of modern and
      disarticulated fossil Ophiuroidea, including brittle stars and basket stars, make
      them an ideal model system for global marine biogeography if we have the
      phylogenetic framework necessary to link extant and fossil morphology in an
      evolutionary context. Here we construct a phylogeny from a highly complete 425
      gene, 61-taxa transcriptome-based data set covering 15 of the 18 ophiuroid
      families and representatives of all extant echinoderm classes. We calibrate our
      phylogeny with a series of novel fossil discoveries from the early Mesozoic. We
      confirm the traditional paleontological view that ophiuroids are sister to the
      asteroids and date the crown group Ophiuroidea to the mid-Permian (270 +/- 30
      mega-annum). We refute all historical classification schemes of the Ophiuroidea
      based on gross structural characters but find strong congruence with schemes
      based on lateral arm plate microstructure and the temporal appearance of various
      plate morphologies in the fossil record. The verification that these microfossils
      contain phylogenetically informative characters unlocks their potential to
      advance our understanding of marine biogeographical processes.

PMID- 25065753
TI  - Local increases in mechanical tension shape compartment boundaries by biasing
      cell intercalations.
AB  - Mechanical forces play important roles during tissue organization in developing
      animals. Many tissues are organized into adjacent, nonmixing groups of cells
      termed compartments. Boundaries between compartments display a straight
      morphology and are associated with signaling centers that are important for
      tissue growth and patterning. Local increases in mechanical tension at cell
      junctions along compartment boundaries have recently been shown to prevent cell
      mixing and to maintain straight boundaries. The cellular mechanisms by which
      local increases in mechanical tension prevent cell mixing at compartment
      boundaries, however, remain poorly understood. Here, we have used live imaging
      and quantitative image analysis to determine cellular dynamics at and near the
      anteroposterior compartment boundaries of the Drosophila pupal abdominal
      epidermis. We show that cell mixing within compartments involves multiple cell
      intercalations. Frequency and orientation of cell intercalations are unchanged
      along the compartment boundaries; rather, an asymmetry in the shrinkage of
      junctions during intercalation is biased, resulting in cell rearrangements that
      suppress cell mixing. Simulations of tissue growth show that local increases in
      mechanical tension can account for this bias in junctional shrinkage. We conclude
      that local increases in mechanical tension maintain cell populations separate by
      influencing junctional rearrangements during cell intercalation.

PMID- 25065754
TI  - Blood-feeding true bugs in the Early Cretaceous.
AB  - Blood-feeding insects, as vectors of disease for humans and livestock alike, have
      garnered significant interest, but our understanding of their early evolution is
      hindered by the scarcity of available material and the difficulty in
      distinguishing early hematophages from non-blood-feeding relatives. Here, we
      report a new family of true bugs including two new genera and species from the
      Early Cretaceous Yixian Formation in Northeastern China. By utilizing geochemical
      methods for determining their diets and combining morphological and taphonomic
      data, we demonstrate that these new species represent the earliest evidence of
      blood feeding among true bugs, extending the geological record of such lineages
      by approximately 30 million years. Remarkably, one of the bugs appears to have
      perished immediately following a blood meal, which may have been from coexisting
      mammals, birds, or avian-related dinosaurs. These records expand the phylogenetic
      and ecological diversity of blood-feeding insects in the Early Cretaceous,
      enriching our knowledge of paleoecological associations in these ancient
      environments.

PMID- 25065755
TI  - Representation of object weight in human ventral visual cortex.
AB  - Skilled manipulation requires the ability to predict the weights of viewed
      objects based on learned associations linking object weight to object visual
      appearance. However, the neural mechanisms involved in extracting weight
      information from viewed object properties are unknown. Given that ventral visual
      pathway areas represent a wide variety of object features, one intriguing but as
      yet untested possibility is that these areas also represent object weight, a
      nonvisual motor-relevant object property. Here, using event-related fMRI and
      pattern classification techniques, we tested the novel hypothesis that object
      sensitive regions in occipitotemporal cortex (OTC), in addition to traditional
      motor-related brain areas, represent object weight when preparing to lift that
      object. In two studies, the same participants prepared and then executed lifting
      actions with objects of varying weight. In the first study, we show that when
      lifting visually identical objects, where predicted weight is based solely on
      sensorimotor memory, weight is represented in object-sensitive OTC. In the second
      study, we show that when object weight is associated with a particular surface
      texture, that texture-sensitive OTC areas also come to represent object weight.
      Notably, these texture-sensitive areas failed to carry information about weight
      in the first study, when object surface properties did not specify weight. Our
      results indicate that the integration of visual and motor-relevant object
      information occurs at the level of single OTC areas and provide evidence that the
      ventral visual pathway is actively and flexibly engaged in processing object
      weight, an object property critical for action planning and control.

PMID- 25065756
TI  - Seamless tube shape is constrained by endocytosis-dependent regulation of active
      Moesin.
AB  - Most tubes have seams (intercellular or autocellular junctions that seal
      membranes together into a tube), but "seamless" tubes also exist. In Drosophila,
      stellate-shaped tracheal terminal cells make seamless tubes, with single branches
      running through each of dozens of cellular extensions. We find that mutations in
      braided impair terminal cell branching and cause formation of seamless tube
      cysts. We show that braided encodes Syntaxin7 and that cysts also form in cells
      deficient for other genes required either for membrane scission (shibire) or for
      early endosome formation (Rab5, Vps45, and Rabenosyn-5). These data define a
      requirement for early endocytosis in shaping seamless tube lumens. Importantly,
      apical proteins Crumbs and phospho-Moesin accumulate to aberrantly high levels in
      braided terminal cells. Overexpression of either Crumbs or phosphomimetic Moesin
      induced lumenal cysts and decreased terminal branching. Conversely, the braided
      seamless tube cyst phenotype was suppressed by mutations in crumbs or Moesin.
      Indeed, mutations in Moesin dominantly suppressed seamless tube cyst formation
      and restored terminal branching. We propose that early endocytosis maintains
      normal steady-state levels of Crumbs, which recruits apical phosphorylated
      (active) Moe, which in turn regulates seamless tube shape through modulation of
      cortical actin filaments.

PMID- 25065758
TI  - Dynamic microtubules catalyze formation of navigator-TRIO complexes to regulate
      neurite extension.
AB  - Neurite extension is regulated by multiple signaling cascades that ultimately
      converge on the actin and microtubule networks [1]. Rho GTPases, molecular
      switches that oscillate between an inactive, GDP-bound state and an active, GTP
      bound state, play a pivotal role in controlling actin cytoskeleton dynamics in
      the growth cone, whereas the dynamic behavior and interactions of microtubules
      are largely regulated by proteins called plus-end-tracking proteins (+TIPs),
      which associate with the ends of growing microtubules. Here, we show that the
      +TIP Navigator 1 (NAV1) is important for neurite outgrowth and interacts and
      colocalizes with TRIO, a Rho guanine nucleotide exchange factor that enables
      neurite outgrowth by activating the Rho GTPases Rac1 and RhoG. We find that
      binding of NAV1 enhances the affinity of TRIO for Rac1 and RhoG, and that NAV1
      regulates TRIO-mediated Rac1 activation and neurite outgrowth. TRIO is also a
      +TIP, as it interacts with the core +TIP EB1 and tracks microtubule plus ends via
      EB1 and NAV1. Strikingly, the EB1-mediated recruitment of TRIO to microtubule
      ends is required for proper neurite outgrowth, and stabilization of the
      microtubule network by paclitaxel affects both the TRIO-NAV1 interaction and the
      accumulation of these proteins in neurite extensions. We propose that EB1-labeled
      ends of dynamic microtubules facilitate the formation and localization of
      functional NAV1-TRIO complexes, which in turn regulate neurite outgrowth by
      selectively activating Rac1. Our data reveal a novel link between dynamic
      microtubules, actin cytoskeleton remodeling, and neurite extension.

PMID- 25065757
TI  - Tension-sensitive actin assembly supports contractility at the epithelial zonula
      adherens.
AB  - BACKGROUND: Actomyosin-based contractility acts on cadherin junctions to support
      tissue integrity and morphogenesis. The actomyosin apparatus of the epithelial
      zonula adherens (ZA) is built by coordinating junctional actin assembly with
      Myosin II activation. However, the physical interaction between Myosin and actin
      filaments that is necessary for contractility can induce actin filament turnover,
      potentially compromising the contractile apparatus itself. RESULTS: We now
      identify tension-sensitive actin assembly as one cellular solution to this design
      paradox. We show that junctional actin assembly is maintained by contractility in
      established junctions and increases when contractility is stimulated. The
      underlying mechanism entails the tension-sensitive recruitment of vinculin to the
      ZA. Vinculin, in turn, directly recruits Mena/VASP proteins to support junctional
      actin assembly. By combining strategies that uncouple Mena/VASP from vinculin or
      ectopically target Mena/VASP to junctions, we show that tension-sensitive actin
      assembly is necessary for junctional integrity and effective contractility at the
      ZA. CONCLUSIONS: We conclude that tension-sensitive regulation of actin assembly
      represents a mechanism for epithelial cells to resolve potential design
      contradictions that are inherent in the way that the junctional actomyosin system
      is assembled. This emphasizes that maintenance and regulation of the actin
      scaffolds themselves influence how cells generate contractile tension.

PMID- 25065760
TI  - A survey of the current state of hip arthroplasty surveillance in the United
      Kingdom.

PMID- 25065759
TI  - Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle
      transport.
AB  - In animal cells, microtubule and actin tracks and their associated motors
      (dynein, kinesin, and myosin) are thought to regulate long- and short-range
      transport, respectively. Consistent with this, microtubules extend from the
      perinuclear centrosome to the plasma membrane and allow bidirectional cargo
      transport over long distances (>1 MUm). In contrast, actin often comprises a
      complex network of short randomly oriented filaments, suggesting that myosin
      motors move cargo short distances. These observations underpin the "highways and
      local roads" model for transport along microtubule and actin tracks. The
      "cooperative capture" model exemplifies this view and suggests that melanosome
      distribution in melanocyte dendrites is maintained by long-range transport on
      microtubules followed by actin/myosin-Va-dependent tethering. In this study, we
      used cell normalization technology to quantitatively examine the contribution of
      microtubules and actin/myosin-Va to organelle distribution in melanocytes.
      Surprisingly, our results indicate that microtubules are essential for
      centripetal, but not centrifugal, transport. Instead, we find that microtubules
      retard a centrifugal transport process that is dependent on myosin-Va and a
      population of dynamic F-actin. Functional analysis of mutant proteins indicates
      that myosin-Va works as a transporter dispersing melanosomes along actin tracks
      whose +/barbed ends are oriented toward the plasma membrane. Overall, our data
      highlight the role of myosin-Va and actin in transport, and not tethering, and
      suggest a new model in which organelle distribution is determined by the balance
      between microtubule-dependent centripetal and myosin-Va/actin-dependent
      centrifugal transport. These observations appear to be consistent with evidence
      coming from other systems showing that actin/myosin networks can drive long
      distance organelle transport and positioning.

PMID- 25065761
TI  - Use of liquid chromatography-mass spectrometry (LC-MS) to detect substances of
      nanomolar concentration in the coronary effluent of isolated perfused hearts.
AB  - When the heart is stretched there is an abrupt increase in force that coincides
      with the stretch that is then followed by a second phase that develops slowly
      over a period of minutes, known as the "slow force response", or "SFR". The SFR
      is accompanied by a slow increase in the Ca(2+) transients, but the underlying
      cellular mechanisms are still debated. We therefore devised a simple bioassay
      system to investigate whether stretch released autocrine/paracrine factors that
      could explain the stretch-dependent Ca(2+) influx during the SFR. Our analysis
      was based around a metabolomics approach using tandem mass spectrometry whereby
      secreted compounds were analysed by liquid chromatography mass spectrometry (LC
      MS/MS) at high resolution and accurate mass. Our bioassay consisted of two
      isolated cardiac preparations in series. A sustained stretch was applied to an
      "upstream" Langendorff-perfused heart, whilst monitoring the performance of an un
      stretched, "downstream" trabecula perfused with coronary effluent collected from
      the "upstream" heart. Switching from "un-stretched" to "stretched" coronary
      effluent increased the amplitude of the Ca(2+) transients (340/380) fura-2 ratio)
      in the "downstream" trabeculae from 0.87 +/- 0.04 to 0.94 +/- 0.05 (p < 0.05, n =
      4), and active stress (mN mm(-2)) from 15.4 +/- 1.5 to 19.2 +/- 1.9 (p < 0.01, n
      = 13), confirming the stretch-dependent release of one or more positively
      inotropic factor(s). To identify the factor, coronary effluent samples were
      concentrated by Solid Phase Extraction (SPE) treatment, lyophilised, then
      analysed using a Thermo Finnigan LTQ FT-ICR hybrid mass spectrometer.
      Differential profile data was obtained initially followed by targeting specific
      compounds at elevated levels in the stretched coronary effluent samples.
      Quantitative and statistical analyses of the differential LC-MS/MS results were
      then carried out using SIEVE 2.1, statistical software capable of performing
      differential analysis of peptides and small molecules. A number of substances
      were identified that were different between stretched and unstretched effluents
      (p < 0.01). 

PMID- 25065762
TI  - A bioorthogonal small-molecule-switch system for controlling protein function in
      live cells.
AB  - Chemically induced dimerization (CID) has proven to be a powerful tool for
      modulating protein interactions. However, the traditional dimerizer rapamycin has
      limitations in certain in vivo applications because of its slow reversibility and
      its affinity for endogenous proteins. Described herein is a bioorthogonal system
      for rapidly reversible CID. A novel dimerizer with synthetic ligand of FKBP'
      (SLF') linked to trimethoprim (TMP). The SLF' moiety binds to the F36V mutant of
      FK506-binding protein (FKBP) and the TMP moiety binds to E. coli dihydrofolate
      reductase (eDHFR). SLF'-TMP-induced heterodimerization of FKBP(F36V) and eDHFR
      with a dissociation constant of 0.12 MUM. Addition of TMP alone was sufficient to
      rapidly disrupt this heterodimerization. Two examples are presented to
      demonstrate that this system is an invaluable tool, which can be widely used to
      rapidly and reversibly control protein function in vivo. 

PMID- 25065763
TI  - Exploration of novel rhizospheric yeast isolate as fertilizing soil inoculant for
      improvement of maize cultivation.
AB  - BACKGROUND: Chemical input in agriculture is a common practice but makes a
      serious impact to the environment. In this context, soil isolates having multiple
      plant growth-promoting (PGP) attributes have been studied. The isolates were
      tested for their PO4 and Zn solubilization, indole-3-acetic acid (IAA) production
      and N2 fixation ability. The selected isolate SSm-39 was characterized to
      molecular level. The isolate SSm-39 was applied to maize cultivation in various
      combinations with chemical fertilizers. Also, the chemical and microbial status
      of soil, its effect on maize growth and yield were investigated. RESULTS: Isolate
      SSm-39 found most suitable for its PGP attributes and identified as Candida
      tropicalis. The inoculant (100%) with reduced dose of chemical fertilizer (T5)
      application notably increased the growth and yield performance of maize. It has
      improved grain quality by 85% as indicated by carbohydrate and protein content,
      in comparison to uninoculated control (T3). Soil nutrient status was found to
      increase twofold with T5 treatment compared with T3 treatment. Enhanced soil
      nutrient quality supported microbial growth and diversity, thus accelerating soil
      enzymatic activities. CONCLUSION: The results validate the multiple PGP traits of
      C. tropicalis SSm-39, advocating reduction of chemical fertilizer for maize
      cultivation.

PMID- 25065765
TI  - Self-other agreement of personality judgments in job interviews: exploring the
      effects of trait, gender, age and social desirability.
AB  - The article investigated agreement between self-reports and stranger ratings of
      personality. A sample of 139 real-life job applicants was interviewed by expert
      psychologists upon entrance to the assessment center. The applicants provided
      self-descriptions on 15 personality factors, and the psychologists rated the same
      traits of each target based on their impressions in the interview. The results
      demonstrated that professional judges can reach a substantial self-other
      agreement (SOA) on several traits even when the targets are strangers, and that
      the trait being judged, the target's gender, age and social desirability have an
      effect on the level of agreement. 

PMID- 25065764
TI  - Control of Maillard-type off-flavor development in ultrahigh-temperature
      processed bovine milk by phenolic chemistry.
AB  - The application of phenolic compounds to suppress Maillard chemistry and off
      flavor development in ultrahigh-termperature (UHT)-processed milk during
      processing and storage was investigated. Five phenolic compounds were examined
      for structure-reactivity relationships (catechin, genistein, daidzein, 1,2,3
      trihydroxybenzene, and 1,3,5-trihydroxybenzene). The levels of key transient
      Maillard reaction (MR) intermediates (reactive carbonyl species) and select off
      flavor markers (methional, 2-acetyl-2-thiazoline, 2-acetyl-1-pyrroline) were
      quantified by LC-MS/MS and GC-MS/ToF, respectively. The addition of phenolic
      compounds prior to UHT processing significantly reduced the concentration of MR
      intermediates and related off-flavor compounds compared to a control sample (p <
      0.05). All phenolic compounds demonstrated unique structure reactivity and,
      notably, those with a more activated A-ring for aromatic electrophilic
      substitution (catechin, genistein, and 1,3,5-trihydroxybenzene) showed the
      strongest suppression effect on the off-flavor markers and reactive carbonyl
      species. Sensory studies were in agreement with the analytical data. The cooked
      flavor intensity was rated lower for the recombination model samples of the
      catechin-treated UHT milk compared to the control UHT milk. Additionally,
      consumer acceptability studies showed catechin-treated UHT milk to have
      significantly higher liking scores when compared the control sample (Fisher's LSD
      = 0.728). 

PMID- 25065766
TI  - Adverse childhood experiences influence white matter microstructure in patients
      with bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BD) is associated with adverse childhood
      experiences (ACE), which worsen the lifetime course of illness, and with signs of
      widespread disruption of white matter (WM) integrity in adult life. ACE are
      associated with changes in WM microstructure in healthy humans. METHOD: We tested
      the effects of ACE on diffusion-tensor imaging (DTI) measures of WM integrity in
      80 in-patients affected by a major depressive episode in the course of BD. We
      used whole-brain tract-based spatial statistics in the WM skeleton with threshold
      free cluster enhancement of DTI measures of WM microstructure: axial, radial and
      mean diffusivity, and fractional anisotropy. RESULTS: ACE hastened the onset of
      illness. We observed an inverse correlation between the severity of ACE and DTI
      measures of axial diffusivity in several WM fibre tracts contributing to the
      functional integrity of the brain and including the corona radiata, thalamic
      radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus,
      inferior fronto-occipital fasciculus and uncinate fasciculus. CONCLUSIONS: Axial
      diffusivity reflects the integrity of axons and myelin sheaths, and correlates
      with functional connectivity and with higher-order abilities such as reasoning
      and experience of emotions. In patients with BD axial diffusivity is increased by
      lithium treatment. ACE might contribute to BD pathophysiology by hampering
      structural connectivity in critical cortico-limbic networks.

PMID- 25065767
TI  - Guar gum solutions for improved delivery of iron particles in porous media (part
      1): porous medium rheology and guar gum-induced clogging.
AB  - The present work is the first part of a comprehensive study on the use of guar
      gum to improve delivery of microscale zero-valent iron particles in contaminated
      aquifers. Guar gum solutions exhibit peculiar shear thinning properties, with
      high viscosity in static conditions and lower viscosity in dynamic conditions:
      this is beneficial both for the storage of MZVI dispersions, and also for the
      injection in porous media. In the present paper, the processes associated with
      guar gum injection in porous media are studied performing single-step and multi
      step filtration tests in sand-packed columns. The experimental results of single
      step tests performed by injecting guar gum solutions prepared at several
      concentrations and applying different dissolution procedures evidenced that the
      presence of residual undissolved polymeric particles in the guar gum solution may
      have a relevant negative impact on the permeability of the porous medium,
      resulting in evident clogging. The most effective preparation procedure which
      minimizes the presence of residual particles is dissolution in warm water (60
      degrees C) followed by centrifugation (procedure T60C). The multi-step tests
      (i.e. injection of guar gum at constant concentration with a step increase of
      flow velocity), performed at three polymer concentrations (1.5, 3 and 4g/l)
      provided information on the rheological properties of guar gum solutions when
      flowing through a porous medium at variable discharge rates, which mimic the
      injection in radial geometry. An experimental protocol was defined for the
      rheological characterization of the fluids in porous media, and empirical
      relationships were derived for the quantification of rheological properties and
      clogging with variable injection rate. These relationships will be implemented in
      the second companion paper (Part II) in a radial transport model for the
      simulation of large-scale injection of MZVI-guar gum slurries. 

PMID- 25065768
TI  - Hypertrichosis of the malar areas and poliosis of the eyelashes caused by
      latanoprost.

PMID- 25065769
TI  - Review article: Maxillofacial emergencies: oral pain and odontogenic infections.
AB  - Oral pain and odontogenic infections are common reasons for patients to present
      to EDs and general medical practice in Australia. Although most odontogenic
      infections can be managed on an outpatient basis, because of their proximity to
      the airway, infections in this region can be life threatening, requiring urgent
      surgical intervention and ICU management. This article focuses on the emergency
      assessment, triage and non-specialist management of oral pain and odontogenic
      infections. 

PMID- 25065770
TI  - Mid-level providers and emergency care: let's not lose the force.
AB  - The progressive rise of ED visits globally, and insufficient numbers of emergency
      physicians, has resulted in the use of mid-level providers as adjuncts for the
      provision of emergency care, especially in the US and Canada. Military medics,
      midwives, aeromedical paramedics, EMT-Ps, flight nurses, forensic nurses, sexual
      assault nurse examiner nurses--are some examples of well-established mid-level
      provider professionals who achieve their clinical credentials through accredited
      training programmes and formal certification. In emergency medicine, however, mid
      level providers are trained for general care, and typically acquire emergency
      medicine skills through on-the-job experience. There are very few training
      programmes for NPs and PAs in emergency care. The manpower gap for physicians in
      general, and emergency physicians specifically, will not be eliminated in the
      reasonable future. Mid-level providers--ENTs, paramedics, NPs, PAs--are an
      excellent addition to the emergency medicine workforce. However, the specialty of
      emergency medicine developed because specific and focused training was needed for
      physicians to practice safe and qualify emergency care. This same principle
      applies to mid-level providers. Emergency Medicine needs to develop a vision and
      a plan to train emergency medicine specialist NPs and PAs, and explore other
      innovations to expand our emergency care workforce.

PMID- 25065772
TI  - Gap junction proteins in the blood-brain barrier control nutrient-dependent
      reactivation of Drosophila neural stem cells.
AB  - Neural stem cells in the adult brain exist primarily in a quiescent state but are
      reactivated in response to changing physiological conditions. How do stem cells
      sense and respond to metabolic changes? In the Drosophila CNS, quiescent neural
      stem cells are reactivated synchronously in response to a nutritional stimulus.
      Feeding triggers insulin production by blood-brain barrier glial cells,
      activating the insulin/insulin-like growth factor pathway in underlying neural
      stem cells and stimulating their growth and proliferation. Here we show that gap
      junctions in the blood-brain barrier glia mediate the influence of metabolic
      changes on stem cell behavior, enabling glia to respond to nutritional signals
      and reactivate quiescent stem cells. We propose that gap junctions in the blood
      brain barrier are required to translate metabolic signals into synchronized
      calcium pulses and insulin secretion. 

PMID- 25065773
TI  - Encoding of temporal signals by the TGF-beta pathway and implications for
      embryonic patterning.
AB  - Genetics and biochemistry have defined the components and wiring of the signaling
      pathways that pattern the embryo. Among them, the transforming growth factor beta
      (TGF-beta) pathway has the potential to behave as a morphogen: in vitro
      experiments established that it can dictate cell fate in a concentration
      dependent manner. How morphogens convey positional information in a developing
      embryo, when signal levels change with time, is less understood. Using integrated
      microfluidic cell culture and time-lapse microscopy, we demonstrate here that the
      speed of ligand presentation has a key and previously unexpected influence on TGF
      beta signaling outcomes. The response to a TGF-beta concentration step is
      transient and adaptive: slowly increasing the ligand concentration diminishes the
      response, and well-spaced pulses of ligand combine additively, resulting in
      greater pathway output than with constant stimulation. Our results suggest that
      in an embryonic context, the speed of change of ligand concentration is an
      instructive signal for patterning. 

PMID- 25065774
TI  - Comparison of the discontinuation rates and side-effect profiles of pilocarpine
      and cevimeline for xerostomia in primary Sjogren's syndrome.
AB  - OBJECTIVES: There are currently no head-to-head comparisons of sialagogues for
      Primary Sjogren's syndrome (pSS). We compared the tolerability and side effect
      profile of pilocarpine and cevimeline in patients with pSS and determined
      clinical, laboratory and pathological variables associated with therapeutic
      failure. METHODS: We retrospectively reviewed the use of pilocarpine and
      cevimeline in 118 patients with pSS who fulfilled the 2002 American European
      Consensus Group criteria in a University-based setting. Clinical, laboratory and
      pathological baseline variables were collected. Failure of therapy was defined as
      the clinician or patient's decision to stop treatment either due to lack of
      efficacy or side effects. RESULTS: Cevimeline was associated with lower failure
      rates compared to pilocarpine among first-time users: 27% vs. 47% (p=0.02), and
      all users: 32% vs. 61% (p<0.001). Severe sweating was the most frequent side
      effect leading to cessation of therapy and occurred more frequently in
      pilocarpine (25%) than cevimeline (11%) users (p=0.02). Patients who previously
      failed one secretagogue were less likely to discontinue treatment with the other
      agent, 52% of first-time users vs. 27% of second-time users (p=0.004). Only ANA
      positivity was associated with failure: [59% vs. 38%] (p=0.03). CONCLUSIONS: pSS
      patients were more likely to continue cevimeline than pilocarpine long-term due
      to fewer reported side effects with cevimeline. Therapeutic failure of one
      secretagogue did not predict similar results with the other since second time
      users were more likely to continue long-term treatment.

PMID- 25065775
TI  - A short tutorial on item response theory in rheumatology.
AB  - OBJECTIVES: The aim is to familiarize physicians and researchers with the most
      important concepts of item response theory (IRT) and with its usefulness for
      improving test administration and data collection in health care. Special
      attention is given to the versatility of its use within the rheumatic field.
      METHODS: This short tutorial describes the most important basic principles of
      item response theory, including the underlying assumptions, the model parameters,
      and the different models that can be applied. Practical applications are
      discussed to demonstrate the potential utility of IRT within clinical practice.
      RESULTS: IRT has proven to be useful for the development and evaluation of both
      clinical measures as well as patient reported outcomes used for measuring health
      status in observational studies and clinical trials. Promising features of IRT
      for the future of test administration are the assessment of local reliability and
      differential item functioning, the cross-cultural validation or equation of
      instruments, the development of large item banks, and the administration of
      computerised adaptive tests. These modern techniques have the ability to maximise
      measurement precision while simultaneously minimise response burden. CONCLUSIONS:
      IRT provides a theoretical basis for developing alternatives to the existing
      tools for assessing health outcome measures in rheumatology.

PMID- 25065776
TI  - Rheumatological patients undergoing immunosuppressive treatments and parasitic
      diseases: a review of the literature of clinical cases and perspectives to screen
      and follow-up active and latent chronic infections.
AB  - OBJECTIVES: Nowadays, several potent immunosuppressive drugs are available for
      patients with rheumatologic disorders. In general, these treatments are
      acceptably well tolerated. Nevertheless, in patients with rheumatic diseases, who
      are taking immunosuppressive drugs, an increased risk of bacterial, viral and
      fungal, as well as parasitic infections, exists. METHODS: We have reviewed
      literature, on PubMed library, on the topic 'parasitic infections in rheumatic
      disease patients treated with immunosuppressive drugs, including biological
      therapies'. We used no language or time restrictions. Search was concluded on
      January 15th 2014. We grouped all parasitic events among rheumatologic,
      therapeutically immuosuppressed, patients to estimate the magnitude of this risk.
      Then we gave our viewpoint in the perspective to screen and follow-up for active
      and latent chronic parasitoses, developing an hypothetical flow-chart. RESULTS:
      From data published in the literature the real burden of parasitoses, among
      patients with rheumatic diseases treated with immunosuppressive treatments, can
      not be estimated. Nevertheless, a positive trend on publication number exists,
      probably due to more than one reason: i) the increasing number of patients
      treated, especially with more than one immunosuppressive treatment, including new
      biological agents; ii) the increasing number of individuals who move from the
      north to the south of the world (endemic areas for parasitic infections) and vice
      versa, due to globalisation, and iii) the fact that more attention is paid for
      notification/publication of cases. CONCLUSIONS: Considering parasitic infections
      as emerging and potentially serious in their evolution, additional strategies for
      the prevention, careful screening and follow-up, with a high level of suspicion,
      identification, and pre-emptive therapy are necessary in candidate patients for
      biological agents.

PMID- 25065777
TI  - A standardized clinical and radiological follow-up of patients with chronic non
      bacterial osteomyelitis treated with pamidronate.
AB  - OBJECTIVES: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory
      disorder of the skeletal system. Treatment with NSAIDs is generally effective in
      the majority of patients, however, a sizeable proportion of patients have
      persistent disease and subsequent treatment strategies are required. The aim of
      this study was to characterise the clinical and radiological disease course in
      CNO patients treated with the bisphosphonate pamidronate (PAM). METHODS: Eight
      CNO patients refractory to NSAIDs, glucocorticoids and sulfasalazine were treated
      with 6 cycles of PAM in four-weekly intervals. The disease course was assessed by
      clinical examination and whole-body (WB) MRI at standardised time points during
      the treatment phase and in a 6 months follow-up. RESULTS: Seven patients were in
      complete clinical remission after 6 applications of PAM. WB MRIs showed
      regression of inflammatory lesions in 7 patients with complete remission in only
      one patient and partial remission in 6 patients. One patient developed
      radiological progression despite a marked improvement of clinical symptoms. In
      the follow-up after PAM therapy, 3 patients developed MRI confirmed relapse.
      Additional applications of PAM induced a sustained clinical remission and partial
      radiological response in two of them. Mild temporary adverse effects were noted
      in 5 patients. CONCLUSIONS: Our study highlights that PAM is effective in
      controlling clinical symptoms (e.g. pain) in CNO patients. However, subclinical
      bone inflammation was still detectable by MRI in most of the patients and disease
      progression was noticed in some patients after cessation of PAM.

PMID- 25065778
TI  - Lymphoma presenting as secondary HLH: a review with a tale of two cases.

PMID- 25065779
TI  - Relative receptor tyrosine kinases and anti-apoptotic transcripts hold potential
      for predicting inferior outcome in adult acute myeloid leukemia: a prospective
      pilot study.
AB  - INTRODUCTION: Acute myeloid leukemia is characterized by accumulation of immature
      cells because of imbalance between proliferation and apoptosis. In AML,
      simultaneous expression of proliferative (FLT-3, c-KIT) and antiapoptotic genes
      (BCL-2), are unknown. PATIENTS AND METHODS: We prospectively assessed
      proliferative and antiapoptotic gene transcripts using Taqman probe chemistry in
      48 adult AML patients. A stepwise Cox regression model was applied for
      independent prognostic factors. RESULTS: Thirty-two of 48 (75%) patients achieved
      complete remission. At follow-up ranging from 0.5 to 57.3 months, event-free
      survival (EFS) was 26.9 +/- 6.3% (range, 15.5%-39.6%) and OS 34.5 +/- 7.46%
      (range, 20.5%-48.9%). High white blood cell count correlated with an inferior
      complete remission rate (P = .021). Cytogenetics and FLT-3 internal tandem
      duplication did not predict EFS or OS. The transcripts of FLT-3, c-KIT, and BCL-2
      showed a significant linear association with each other in Pearson correlation
      (FLT-3 vs. c-KIT: R = 0.8234; P < .001; c-KIT vs. BCL-2: R = 0.3377; P = .01; FLT
      3 vs. BCL-2: R = 0.3815; P = .007). In a validation cohort (Microarray Data Set
      GSE1159) of adult AML patients, the global gene expression profile depicted a
      similar interrelationship. Patients with a greater platelet count were associated
      with increased transcript levels of BCL-2 (P = .034). In univariate analysis, a
      high transcript level of FLT-3 and high transcript ratio of FLT-3/BCL-2 and FLT-3
      and c-KIT/BCL-2 significantly predicted OS (P = .043, .028, and .028,
      respectively). In a stepwise Cox regression model, high FLT-3 and c-KIT/BCL-2
      ratio predicted OS (HR, 2.29). CONCLUSION: To our knowledge, this is the first
      study that evaluated proliferative and antiapoptotic transcripts simultaneously,
      and results have shown that it is the relative levels of these transcripts that
      determine outcome in AML patients rather than their expression in isolation.

PMID- 25065780
TI  - Dermato-neuro syndrome in a patient treated with autologous stem cell transplant
      for scleromyxedema.

PMID- 25065781
TI  - One-pot decarboxylative acylation of N-, O-, S-nucleophiles and peptides with 2,2
      disubstituted malonic acids.
AB  - Monocarbonyl activation of 2,2-disubstituted malonic acids with benzotriazole
      leads to decarboxylation of one of the carboxy groups and formation of a C?H
      bond. Intermediate carbonyl benzotriazoles then readily acylate nucleophilic
      reagents and peptides resulting in libraries of conjugates and peptidomimetics. 

PMID- 25065782
TI  - Examining thiosulfate-driven autotrophic denitrification through respirometry.
AB  - Anoxic respirometry was applied to characterize a sulfide-oxidizing nitrate
      reducing (SO-NR) culture obtained from an anoxic biogas desulfurizing
      biotrickling filter treating high loads of H2S. Immobilized biomass extracted
      from the biotrickling filter was grown in a suspended culture with thiosulfate as
      electron donor to obtain the biomass growth yield and the S2O3(2)(-)/NO3(-)
      consumed ratio. Afterward, respirometry was applied to describe thiosulfate
      oxidation under anoxic conditions. A pure culture of Thiobacillus denitrificans
      was also used as a control culture in order to validate the procedure proposed in
      this work to characterize the SO-NR biomass. Respirometric profiles obtained with
      this microbial culture showed that nitrite was formed as intermediate during
      nitrate reduction and revealed that no competitive inhibition appeared when both
      electron acceptors were present in the medium. Although final bioreaction
      products depended on the initial S2O3(2)(-)/NO3(-) ratio, such ratio did not
      affect thiosulfate oxidation or denitrification rates. Moreover, respirometric
      profiles showed that the specific nitrite uptake rate depended on the biomass
      characteristics being that of a SO-NR mixed culture (39.8mgNg(-1) VSSh(-1))
      higher than that obtained from a pure culture of T. denitrificans (19.7mgNg(-1)
      VSSh(-1)). For the first time, the stoichiometry of the two-step denitrification
      mechanism with thiosulfate oxidation and biomass growth associated was solved for
      both reactions. 

PMID- 25065783
TI  - Characterization of arsenic-resistant endophytic bacteria from hyperaccumulators
      Pteris vittata and Pteris multifida.
AB  - We isolated and characterized As-resistant endophytic bacteria (AEB) from two
      arsenic hyperaccumulators. Their plant growth promoting traits and the relation
      between As tolerance and transformation were evaluated. A total of 41 and 33 AEB
      were isolated from Pteris vittata (PV) and Pteris multifida (PM) respectively. PV
      AEB represented 2genera while PM AEB comprised of 12 genera, with Bacillus sp.
      being the most dominant bacteria from both plants. All AEB had limited ability in
      solubilizing P and producing indole acetic acid (IAA) and siderophore. All
      isolates tolerated 10mM arsenate (As(V)), with PV isolates being more tolerant to
      As(V) and PM more tolerant to arsenite (As(III)). Bacterial arsenic tolerance was
      related to their ability in As(III) oxidation and As(V) reduction as well as
      their ability to retain As in the biomass to a varying extent. Though AEB showed
      limited plant growth promoting traits, they were important in arsenic tolerance
      and speciation in plants. 

PMID- 25065784
TI  - Fungal transformation of metallic lead to pyromorphite in liquid medium.
AB  - Many approaches have been proposed to reduce the toxicity of hazardous substances
      such as lead in the environment. Several techniques using microorganisms rely on
      metal removal from solution by non-specific biosorption. However, immobilization
      of metals through formation of biominerals mediated by metabolic processes offers
      another solution but which has been given limited attention. In this work, we
      have investigated lead biomineralization by Paecilomyces javanicus, a fungus
      isolated from a lead-contaminated soil, in a liquid medium. P. javanicus was able
      to grow in the presence of metallic lead, supplied as lead shot, and secondary
      lead minerals were deposited on the lead surfaces as revealed by scanning
      electron microscopy. Energy dispersive X-ray analysis and X-ray powder
      diffraction revealed that pyromorphite was formed in the presence of the fungus,
      but not in abiotic controls. Our results clearly demonstrate that fungal
      activities can play an important role in lead biocorrosion and biomineralization
      in an aqueous environment. These findings are relevant to bioremediation
      approaches for liquid wastes contaminated with lead, or other metals, and also to
      the immobilization and biorecovery of rare or valuable elements. They also
      provide further understanding of microbial roles in environmental lead cycling. 

PMID- 25065785
TI  - Characterization of the biochemical-pathway of uranium (VI) reduction in
      facultative anaerobic bacteria.
AB  - Cultures of U(VI) reducing bacteria sourced from abandoned uranium mine tailing
      dam were evaluated for their ability to reduce U(VI) to U(IV). The species in the
      cultures reduced U(VI) in solutions with initial U(VI) concentration up to
      400mgL(-)(1) under a near neutral pH of 6.5. The electron flow pathway and fate
      of reduced species was also analysed in the individual species in order to
      evaluate the potential for control and optimisation of the reduction potential at
      the biochemical level. The results showed that U(VI) reduction in live cells was
      completely blocked by the NADH-dehydrogenase inhibitor, rotenone (C23H22O6), and
      thioredoxin inhibitor, cadmium chloride (CdCl2), showing that U(VI) reduction
      involves the electron flow through NADH-dehydrogenase, a primary electron donor
      to the electron transport respiratory (ETR) system. Mass balance analysis of
      uranium species aided by visual and electron microscopy suggest that most U(VI)
      reduction occurred on the cell surface of the isolated species. This finding
      indicates the possibility of easy uranium recovery for beneficial use through
      biological remediation. Should the U(VI) be reduced inside the cell, recovery
      would require complete disruption of the cells and therefore would be difficult.
      The study contributes new knowledge on the underlying mechanisms in the U(VI)
      reduction in facultative anaerobes. 

PMID- 25065786
TI  - Effects of d-menthol stress on the growth of and microcystin release by the
      freshwater cyanobacterium Microcystis aeruginosa FACHB-905.
AB  - The effects of d-menthol on the growth of Microcystis aeruginosa FACHB-905 and
      microcystin (MCY) concentration were evaluated by batch culture experiments. The
      algal biomass and the intracellular and extracellular MCY concentrations were
      evaluated during 5d incubation. After the d-menthol exposure, the dry weight of
      the cells gradually decreased; the decrease in the dry weight after 5d exposure
      was 29, 12, and 2mgL(-1) when the initial cell densities were 1.4*10(7),
      1.2*10(6), and 2.9*10(5)cellmL(-1), respectively. The results indicate that the d
      menthol exposure inhibited the cellular growth, thus also inhibiting the increase
      of the total MCY concentration. In the presence of d-menthol, the intracellular
      MCY was gradually released into the medium after the cell lysis. The
      extracellular MCY concentration in the medium was significantly higher in the d
      menthol-exposed samples than in the control samples, confirming that d-menthol
      cannot decompose the extracellular MCY. 

PMID- 25065787
TI  - Formation of abiological granular sludge - a facile and bioinspired proposal for
      improving sludge settling performance during heavy metal wastewater treatment.
AB  - Heavy metal contamination in wastewater poses a severe threat to the environment
      and public health. Chemical precipitation is the most conventional process for
      heavy metal wastewater treatment. However, the flocculent structure of chemical
      precipitation sludge raises the problem of poor sludge settling performance that
      is difficult to overcome. Inspired by the biological granular sludge (BGS)
      formation process, we report here a facile and effective strategy to produce
      abiological granular sludge (ABGS) to solve this problem. In this procedure,
      controlled double-jet precipitation was performed to simulate the cell
      multiplication process in BGS formation by controlling the solution
      supersaturation. Meanwhile, ZnO seeds and flocculant polyacrylamide were added to
      simulate the role of nuclei growth and extracellular polymeric substances in BGS
      formation process, respectively. This procedure generates ABGS with a dense
      structure, large size and regular spherical morphology. The settling velocity of
      ABGS can reach up to 3.0cms(-1), significantly higher than that of flocculent
      sludge (<1cms(-1)). 

PMID- 25065788
TI  - Is vetiver grass of interest for the remediation of Cu and Cd to protect
      marketing gardens in Burkina Faso?
AB  - In Burkina-Faso, urban vegetable agriculture is often characterized by urban
      solid waste fertilizer inputs containing heavy metals such as Cu and Cd. Thus,
      the relevance of surrounding urban vegetable plots with vetiver hedges to reduce
      environmental pollution by Cu and Cd was investigated by adsorption studies and
      pot experiments. Vetiver biomass, its metal contents and, its total and MgCl2
      extractable soil metals were monitored over 6months in the presence of a mixture
      of metal at two concentrations: 2-10 and 100-500mgkg(-1), for Cd and Cu,
      respectively. The Freundlich adsorption coefficient (Kf) values increased after
      vetiver growth and were significantly higher for vertisol than for lixisol. After
      6months, the vetiver that was grown on lixisol accumulated more metal, increasing
      up to 4635mgkg(-1) for Cu and to 21.8mgkg(-1) for Cd, than did the vetiver that
      was grown on vertisol, increasing up to 1534mgkg(-1) for Cu and to 7.2mgkg(-1)
      for Cd. The metal bioconcentration factor, which was significantly higher for Cd,
      increased with the applied concentration and ranged from 1.6 to 14 for Cu and
      from 2.3 to 22 for Cd. Additionally, the translocation factors were higher for Cd
      (0.38-7.3) than for Cu (0.07-2.6), and the translocation was easiest from lixisol
      than from vertisol. Thus our results demonstrate the ability of vetiver for Cu
      and Cd phytoremediation in Burkina Faso soils. Nevertheless, these results should
      be confirmed across the field to advocate the establishment of vetiver hedges. 

PMID- 25065789
TI  - Electrochemical degradation of nitrobenzene by anodic oxidation on the
      constructed TiO2-NTs/SnO2-Sb/PbO2 electrode.
AB  - The interlayer of Sb-doped SnO2 (SnO2-Sb) and TiO2 nanotubes (TiO2-NTs) on Ti has
      been introduced into the PbO2 electrode system with the aim to reveal the
      mechanism of enhanced electrochemical performance of TiO2-NTs/SnO2-Sb/PbO2
      electrode. In contrast with the traditional Ti/SnO2-Sb/PbO2 electrode, the
      constructed PbO2 electrode has a more regular and compact morphology with better
      oriented crystals of lower size. The TiO2-NTs/SnO2-Sb interlayer prepared by
      electrodeposition process improves PbO2 coating structure effectively, and
      enhances the electrochemical performance of PbO2 electrode. Kinetic analyses
      indicated that the electrochemical oxidation of nitrobenzene on the PbO2
      electrodes followed pseudo-first-order reaction, and mass transport was enhanced
      at the constructed electrode. The accumulation of nitrocompounds of degradation
      intermediates on constructed electrode was lower, and almost all of the nitro
      groups were eliminated from aromatic rings after 6h of electrolysis. Higher
      combustion efficiency was obtained on the constructed TiO2-NTs/SnO2-Sb/PbO2
      electrode. The intermediates of nitrobenzene oxidation were confirmed by IC and
      GC/MS. 

PMID- 25065790
TI  - Modified Fenton oxidation of diesel fuel in arctic soils rich in organic matter
      and iron.
AB  - Modified Fenton (MF) chemistry was tested in the laboratory to treat three diesel
      fuel-contaminated soils from the Canadian arctic rich in soil organic matter
      (SOM) and Fe oxides. Reactors were dosed with hydrogen peroxide (HP), and
      treatment was compared in reactors with SOM as the only chelate vs. reactors to
      which ethylenediaminetetraacetate (EDTA) was added. Concentrations of diesel fuel
      and HP were measured over time, and the oxidation of both diesel fuel and SOM
      were quantified in each soil. A distinct selectivity for oxidation of diesel fuel
      over SOM was observed. Reactors with EDTA showed significantly less diesel fuel
      oxidation and lower oxidant efficiency (diesel fuel oxidized/HP consumed) than
      reactors with SOM as the only chelate. The results from these studies demonstrate
      that MF chemistry can be an effective remedial tool for contaminated arctic
      soils, and challenge the traditional conceptual model that SOM reduces the
      efficiency of MF treatment through excessive scavenging of oxidant. 

PMID- 25065791
TI  - Olive oil mill wastewaters: phenolic content characterization during degradation
      by Coriolopsis gallica.
AB  - Olive mill wastewaters (OMW) pose a serious environmental concern owing to high
      polyphenol content. Decolorization and degradation of phenolic compounds (PC) by
      Coriolopsis gallica was demonstrated in our laboratory as a potential
      biotreatment of OMW in solid and liquid media. High performance liquid
      chromatography coupled to electrospray time-of-flight mass spectrometry was used
      to analyze the evolution of the main phenolic compounds during the C. gallica
      biodegradation process. Amongst total the compounds characterized in methanolic
      extracts of OMW, 12 were unknown, 15 were from different polyphenolic families,
      and 27 were other non-phenolic compounds. The evolution of PC content during the
      degradation process indicated that, despite the complexity of the OMW phenolic
      fraction, C. gallica was able to grow on OMW-based media using PC as sources of
      carbon and energy, particularly acids, alcohols, lignans and flavones. Complete
      dephenolization of OMW was obtained. 

PMID- 25065792
TI  - Solar photocatalytic ozonation of a mixture of pharmaceutical compounds in water.
AB  - Aqueous solutions of mixtures of four pharmaceutical compounds (atenolol,
      hydrochlorothiazide, ofloxacin and trimethoprim) both in Milli-Q ultrapure water
      and in a secondary effluent from a municipal wastewater treatment plant have been
      treated at pH 7 by different oxidation methods, such as conventional ozonation,
      photolytic ozonation, TiO2 catalytic ozonation, TiO2 photocatalytic oxidation and
      TiO2 photocatalytic ozonation. Experiments were carried out using a solar
      compound parabolic concentrator. The performance results have been compared in
      terms of removal of emerging contaminants (ECs), generation rate of phenolic
      intermediates, organic matter mineralization, ecotoxicity removal and enhancement
      of biodegradability. Also, the consumption of ozone to achieve certain treatment
      goals (95% removal of ECs and 40% mineralization) is discussed. Results reveal
      that solar photocatalytic ozonation is a promising oxidation method as it led to
      the best results in terms of EC mineralization (~85%), toxicity removal (~90%)
      and efficient use of ozone (~2mgO3mgEC(-1) to achieve complete EC removal and
      ~18mgO3mgTOC(-1) to achieve 40% EC mineralization, respectively). 

PMID- 25065793
TI  - Identifying changes in dissolved organic matter content and characteristics by
      fluorescence spectroscopy coupled with self-organizing map and classification and
      regression tree analysis during wastewater treatment.
AB  - The stabilization of latent tracers of dissolved organic matter (DOM) of
      wastewater was analyzed by three-dimensional excitation-emission matrix (EEM)
      fluorescence spectroscopy coupled with self-organizing map and classification and
      regression tree analysis (CART) in wastewater treatment performance. DOM of water
      samples collected from primary sedimentation, anaerobic, anoxic, oxic and
      secondary sedimentation tanks in a large-scale wastewater treatment plant
      contained four fluorescence components: tryptophan-like (C1), tyrosine-like (C2),
      microbial humic-like (C3) and fulvic-like (C4) materials extracted by self
      organizing map. These components showed good positive linear correlations with
      dissolved organic carbon of DOM. C1 and C2 were representative components in the
      wastewater, and they were removed to a higher extent than those of C3 and C4 in
      the treatment process. C2 was a latent parameter determined by CART to
      differentiate water samples of oxic and secondary sedimentation tanks from the
      successive treatment units, indirectly proving that most of tyrosine-like
      material was degraded by anaerobic microorganisms. C1 was an accurate parameter
      to comprehensively separate the samples of the five treatment units from each
      other, indirectly indicating that tryptophan-like material was decomposed by
      anaerobic and aerobic bacteria. EEM fluorescence spectroscopy in combination with
      self-organizing map and CART analysis can be a nondestructive effective method
      for characterizing structural component of DOM fractions and monitoring organic
      matter removal in wastewater treatment process. 

PMID- 25065794
TI  - Boosting the value of biodiesel byproduct by the non-catalytic
      transesterification of dimethyl carbonate via a continuous flow system under
      ambient pressure.
AB  - Transformation of coconut oil into biodiesel by using dimethyl carbonate (DMC)
      via a non-catalytic transesterification reaction under ambient pressure was
      investigated in this study. The non-catalytic transformation to biodiesel was
      achieved by means of a heterogeneous reaction between liquid triglycerides and
      gas phase DMC. The reaction was enhanced in the presence of porous material due
      to its intrinsic physical properties such as tortuosity and
      absorption/adsorption. The numerous pores in the material served as micro
      reaction chambers and ensured that there was enough contact time between the
      liquid triglycerides and the gaseous DMC, which enabled the completion of the
      transesterification. The highest fatty acid methyl esters (FAMEs) yield achieved
      was 98+/-0.5% within 1-2min at a temperature of 360-450 degrees C under ambient
      pressure. The fast reaction rates made it possible to convert the lipid feedstock
      into biodiesel via a continuous flow system without the application of increased
      pressure. This suggested that the commonly used supercritical conditions could be
      avoided, resulting in huge cost benefits for biodiesel production. In addition,
      the high value of the byproduct from the transesterification of the lipid
      feedstock with DMC suggested that the production biodiesel using this method
      could be more economically competitive. Finally, the basic properties of
      biodiesel derived from the non-catalytic conversion of rapeseed oil with DMC were
      summarised. 

PMID- 25065795
TI  - Effect of anions and humic acid on the performance of nanoscale zero-valent iron
      particles coated with polyacrylic acid.
AB  - Effects of anions (NO3(-), HCO3(-), Cl(-), SO4(2-)) and humic acid on the
      reactivity and core/shell chemistries of polyacrylic acid-coated nanoscale zero
      valent iron (PAA-NZVI) and inorganically modified NZVI (INORG-NZVI) particles
      were investigated. The reactivity tests under various ion concentrations (0.2
      30mN) revealed the existence of a favorable molar ratio of anion/NZVI that
      increased the reactivity of NZVI particles. The presence of a relatively small
      amount of humic acid (0.5mgL(-1)) substantially decreased the INORG-NZVI
      reactivity by 76%, whereas the reactivity of PAA-NZVI decreased only by 12%. The
      XRD and TEM results supported the role of the PAA coating of PAA-NZVI in impeding
      the oxidation of the Fe(0) core by groundwater solutes. This protective role
      provided by the organic coating also resulted in a 2.3-fold increase in the
      trichloroethylene (TCE) reduction capacity of PAA-NZVI compared to that of INORG
      NZVI in the presence of anions/humic acid. Ethylene and ethane were
      simultaneously produced as the major reduction products of TCE in both NZVI
      systems, suggesting that a hydrodechlorination occurred without the aid of
      metallic catalysts. The PAA coating, originally designed to improve the mobility
      of NZVI, enhanced TCE degradation performances of NZVI in the presence of anions
      and humic acid. 

PMID- 25065796
TI  - Diagnostic investigation of steroid estrogen removal by activated sludge at
      varying solids retention time.
AB  - The impact of solids retention time (SRT) on estrone (E1), 17beta-estradiol (E2),
      estriol (E3) and 17alpha-ethinylestradiol (EE2) removal in an activated sludge
      plant (ASP) was examined using a pilot plant to closely control operation. Exsitu
      analytical methods were simultaneously used to enable discrimination of the
      dominant mechanisms governing estrogen removal following transitions in SRT from
      short (3d) to medium (10d) and long (27d) SRTs which broadly represent those
      encountered at full-scale. Total estrogen (?EST, i.e., sum of E1, E2, E3 and EE2)
      removals which account for aqueous and particulate concentrations were 70+/-8,
      95+/-1 and 93+/-2% at 3, 10 and 27d SRTs respectively. The improved removal
      observed following an SRT increase from 3 to 10d was attributable to the
      augmented biodegradation of the natural estrogens E1 and E2. Interestingly,
      estrogen biodegradation per bacterial cell increased with SRT. These were 499,
      1361 and 1750ng 10(12) viable cells(-1)d(-1). This indicated an improved
      efficiency of the same group or the development of a more responsive group of
      bacteria. In this study no improvement in absolute ?EST removal was observed in
      the ASP when SRT increased from 10 to 27d. However, batch studies identified an
      augmented biomass sorption capacity for the more hydrophobic estrogens E2 and EE2
      at 27d, equivalent to an order of magnitude. The lack of influence on estrogen
      removal during pilot plant operation can be ascribed to their distribution within
      activated sludge being under equilibrium. Consequently, lower wastage of excess
      sludge inherent of long SRT operation counteracts any improvement in sorption. 

PMID- 25065797
TI  - Bacterial pathogen indicators regrowth and reduced sulphur compounds' emissions
      during storage of electro-dewatered biosolids.
AB  - Electro-dewatering (ED) increases biosolids dryness from 10-15 to 30-50%, which
      helps wastewater treatment facilities control disposal costs. Previous work
      showed that high temperatures due to Joule heating during ED inactivate total
      coliforms to meet USEPA Class A biosolids requirements. This allows biosolids
      land application if the requirements are still met after the storage period
      between production and application. In this study, we examined bacterial regrowth
      and odour emissions during the storage of ED biosolids. No regrowth of total
      coliforms was observed in ED biosolids over 7d under aerobic or anaerobic
      incubations. To mimic on-site contamination during storage or transport, ED
      samples were seeded with untreated sludge. Total coliform counts decreased to
      detection limits after 4d in inoculated samples. Olfactometric analysis of ED
      biosolids odours showed that odour concentrations were lower compared to the
      untreated and heat-treated control biosolids. Furthermore, under anaerobic
      conditions, odorous reduced sulphur compounds (methanethiol, dimethyl sulphide
      and dimethyl disulphide) were produced by untreated and heat-treated biosolids,
      but were not detected in the headspaces above ED samples. The data demonstrate
      that ED provides advantages not only as a dewatering technique, but also for
      producing biosolids with lower microbial counts and odour levels. 

PMID- 25065799
TI  - High-rate nitrogen removal and microbial community of an up-flow anammox reactor
      with ceramics as biomass carrier.
AB  - Nitrogen removal performance and responsible microbial community of anammox
      process at low temperatures, and long term effect of dissolved oxygen (DO) on the
      performance of anammox process were investigated in a biofilm reactor, which was
      operated at 33+/-1 degrees C (159d) and 20+/-2 degrees C (162d) with an influent
      DO concentration of 0.7-1.5mgL(-1). Nitrogen removal recovered to 70% after 2wk
      with the temperature drastically decreasing from 33+/-1 degrees C to 20+/-2
      degrees C. At 20+/-2 degrees C, the average effluent (NH4(+)-N+NO2(-)-N)
      concentration was 0.08+/-0.08mgL(-1) at a hydraulic retention time of 1.5h. A
      total nitrogen removal efficiency of the reactor of 1.0gNL(-1)d(-1) was obtained
      for up to one month while the nitrogen loading rate was 1.16gNL(-1)d(-1). Results
      of T-RFLP and 16S rRNA phylogenic analysis revealed that Candidatus Jettenia
      asiatica, as confirmed to adapt to low temperature, was considered to be
      responsible for the stable and high nitrogen removal performance. 

PMID- 25065798
TI  - Bioflocculant production and biosorption of zinc and lead by a novel bacterial
      species, Achromobacter sp. TERI-IASST N, isolated from oil refinery waste.
AB  - A bioflocculant-producing bacterial isolate designated as 'TERI-IASST N' was
      isolated from activated sludge samples collected from an oil refinery. This
      isolate demonstrated maximum bioflocculation activity (74%) from glucose among 15
      different bioflocculant-producing bacterial strains isolated from the sludge
      samples and identified as Achromobacter sp. based on 16S rRNA gene sequence.
      Optimization of pH and supplementation of urea as nitrogen source in the
      production medium enhanced the flocculation activity of strain TERI-IASST N to
      84% (at pH 6). This strain revealed maximum flocculation activity (90%) from
      sucrose compared to the flocculation activity observed from other carbon sources
      as investigated (glucose, lactose, fructose, maltose and starch). Ca(2+) served
      as the suitable divalent cation for maximum bioflocculation activity of TERI
      IASST strain N. Maximum flocculation activity was observed at optimum C/N ratio
      of 1. Flocculation activity of this strain decreased to 75% in the presence of
      heavy metals; Zn, Pb, Ni, Cu and Cd. In addition strain N revealed considerable
      biosorption of Zn (430mgL(-1)) and Pb (30mgL(-1)). Bioflocculant yield of strain
      N was 10.5gL(-1). Fourier transform infrared spectrum indicated the presence of
      carboxyl, hydroxyl, and amino groups, typical of glycoprotein. Spectroscopic
      analysis of bioflocculant by nuclear magnetic resonance revealed that it is a
      glycoprotein, consisting of 57% total sugar and 13% protein. 

PMID- 25065800
TI  - Seedling emergence, growth and trace elements tolerance and accumulation by
      Lamiaceae species in a mine soil.
AB  - The potential use of three Laminaceae species (Lavandula dentata, Rosmarinus
      officinalis and Thymus vulgaris) for the phytostabilisation of a trace elements
      contaminated (acid) soil has been evaluated. These species were grown in mine
      tailing soil unamended (TS) and amended with calcium carbonate and pig manure
      (ATS), and unpolluted substrate for control (CT); plant growth, root
      characterisation, soil trace elements contents and their accumulation in plants
      were measured. Results indicated that seed emergence was independent from
      substrate characteristics, but seedlings died in TS with 40% survival in ATS. The
      biomass of L. dentata and T. vulgaris and root development in R. officinalis were
      negatively affected when grown in TS but without differences between ATS and CT.
      Applicating amendments reduced soil exchangeable and extractable fractions
      concentrations of trace elements in ATS compared with TS. The establishment of L.
      dentata and R. officinalis were related to trace elements immobilisation. Trace
      element concentrations in plants grown in tailing soils were similar to those
      reported for control, although applicating amendments reduced Zn accumulation in
      all species, and favoured increased absorption and aerial translocation of As and
      Pb by L. dentata and T. vulgaris; nonetheless, levels were below toxicity
      thresholds. Thus, these species fulfill the criteria for phytostabilisation
      purposes, aided by employing amendments. 

PMID- 25065801
TI  - Bacterial acquisition of hexachlorobenzene-derived carbon in contaminated soil.
AB  - Pesticides are a class of xenobiotics intentionally released into the
      environment. Hexachlorobenzene (HCB) was used as a fungicide from 1945, leaving
      behind many contaminated sites. Very few studies have examined the biodegradation
      of HCB or the fate of HCB-derived carbon. Here we report that certain bacterial
      populations are capable of deriving carbon from HCB in contaminated soil under
      aerobic conditions. These populations are primarily Proteobacteria, including
      Methylobacterium and Pseudomonas, which predominated as detected by stable
      isotope probing (SIP) and 16S rRNA gene amplicon pyrosequencing. Due to the
      nature of SIP, which can be used as a functional method solely for assimilatory
      processes, it is not possible to elucidate whether these populations metabolized
      directly HCB or intermediates of its metabolism produced by different
      populations. The possibility exists that HCB is degraded via the formation of
      pentachlorophenol (PCP), which is further mineralized. With this in mind, we
      designed primers to amplify PCP 4-monooxygenase-coding sequences based on the
      available pcpB gene sequence from Methylobacterium radiotolerans JCM 2831. Based
      on 16S rRNA gene analysis, organisms closely related to this strain were detected
      in (13)C-labeled DNA. Using the designed primers, we were able to amplify pcpB
      genes in both total community DNA and (13)C-DNA. This indicates that HCB might be
      transformed into PCP before it gets assimilated. In summary, this study is the
      first report on which bacterial populations benefit from carbon originating in
      the pesticide HCB in a contaminated soil. 

PMID- 25065802
TI  - Fate of phosphorus in diluted urine with tap water.
AB  - P loss during the fresh urine storage process is inevitable because of the
      presence of Ca and Mg. Dilution is one of the most important parameters
      influencing urine composition and subsequent P recovery. This study aimed to
      investigate the fate of P in urine with different dilution ratios (Vwater/Vurine,
      i.e., 0/100, 25/75, 50/50 and 75/25). The results indicate that the percentage of
      P loss increased from 43% to 76% as the dilution ratio increased from 0/100 to
      75/25 because of more Ca and Mg obtained from tap water. Meanwhile, P removal
      efficiency through struvite precipitation decreased from 51% to 8% because of
      lower supersaturation ratio as a result of dilution. Struvite crystals with high
      purity were still obtained even under a dilution ratio of 50/50 urine solution.
      Batch experiments were also performed to study the influence of temperature (15
      35 degrees C) on P recovery and crystal size. For different dilution ratios of
      urine solutions, no significant discrepancy for the P removal efficiencies were
      observed at 15 and 35 degrees C, whereas the P removal efficiencies at 25 degrees
      C showed an increasing gap with those at 15 and 35 degrees C. The largest average
      crystal sizes were found at 25 degrees C, which was opposite to the trend of P
      removal efficiency. 

PMID- 25065803
TI  - Improved arsenic(III) adsorption by Al2O3 nanoparticles and H2O2: evidence of
      oxidation to arsenic(V) from X-ray absorption spectroscopy.
AB  - We have investigated the oxidation of inorganic As(III) with H2O2 catalysed by
      Al2O3, using X-ray absorption near-edge structure and extended X-ray absorption
      fine structure spectroscopy. The effects of different reaction conditions (pH,
      time and initial H2O2 concentration) were also studied as were the kinetics of
      the oxidation reaction. We demonstrated that As(III) was oxidized to As(V) in the
      presence of H2O2 and Al2O3. Furthermore, all arsenic species found on the Al2O3
      surface were in the As(V) state. The presence of both Al2O3 and H2O2 was
      necessary for oxidation of As(III) to take place within the period of time
      studied. The oxidation kinetics indicate a mechanism where reversible As(III)
      binding to the alumina surface is followed by irreversible oxidation by H2O2
      leading to strongly bound As(V). Results from this study indicate that there is a
      surface-catalysed oxidation of As(III) on Al2O3 by H2O2, a reaction that can take
      place in nature and can be of help in the development of novel treatment systems
      for As(III) removal. 

PMID- 25065804
TI  - Novel insights into anoxic/aerobic(1)/aerobic(2) biological fluidized-bed system
      for coke wastewater treatment by fluorescence excitation-emission matrix spectra
      coupled with parallel factor analysis.
AB  - Fluorescence spectroscopy coupled with parallel factor analysis (PARAFAC) was
      applied to investigate the contaminant removal efficiency and fluorescent
      characteristic variations in a full scale coke wastewater (CWW) treatment plant
      with a novel anoxic/aerobic(1)/aerobic(2) (A/O(1)/O(2)) process, which combined
      with internal-loop fluidized-bed reactor. Routine monitoring results indicated
      that primary contaminants in CWW, such as phenols and free cyanide, were removed
      efficiently in A/O(1)/O(2) process (removal efficiency reached 99% and 95%,
      respectively). Three-dimensional excitation-emission matrix fluorescence
      spectroscopy and PARAFAC identified three fluorescent components, including two
      humic-like fluorescence components (C1 and C3) and one protein-like component
      (C2). Principal component analysis revealed that C1 and C2 correlated with COD
      (correlation coefficient (r)=0.782, p<0.01 and r=0.921, p<0.01), respectively)
      and phenols (r=0.796, p<0.01 and r=0.914, p<0.01, respectively), suggesting that
      C1 and C2 might be associated with the predominating aromatic contaminants in
      CWW. C3 correlated with mixed liquor suspended solids (r=0.863, p<0.01) in
      fluidized-bed reactors, suggesting that it might represent the biological
      dissolved organic matter. In A/O(1)/O(2) process, the fluorescence intensities of
      C1 and C2 consecutively decreased, indicating the degradation of aromatic
      contaminants. Correspondingly, the fluorescence intensity of C3 increased in
      aerobic(1) stage, suggesting an increase of biological dissolved organic matter. 

PMID- 25065805
TI  - Degradation of diclofenac by ultrasonic irradiation: kinetic studies and
      degradation pathways.
AB  - Diclofenac (DCF) is a widely used anti-inflammatory drug found in various water
      bodies, posing threats to human health. In this research, the effects of
      ultrasonic irradiation at 585kHz on the degradation of DCF were studied under the
      air, oxygen, argon, and nitrogen saturated conditions. First, the dechlorination
      efficiencies under the air, oxygen, argon, and nitrogen saturated conditions were
      calculated to be 67%, 60%, 53% and 59%. Second, there was full mineralization of
      nitrogen during DCF degradation under the air, oxygen, and argon saturated
      conditions, but no mineralization of nitrogen under the nitrogen-saturated
      condition. Different from nitrogen, only partial mineralization of carbon
      occurred under the four gas-saturated conditions. Third, OH scavengers were added
      to derive the rate constants in the three reaction zones: cavitation bubble,
      supercritical interface, and bulk solution. Comparison of the constants indicated
      that DCF degradation was not limited to the bulk solution as conventionally
      assumed. Oxidation in the supercritical interface played a dominant role under
      the air and oxygen saturated conditions, while OH reactions in the cavitation
      bubble and/or bulk solution were dominant under the nitrogen and argon saturated
      conditions. After the addition of H2O2, reactions in the cavitation bubble and
      bulk solution kept their dominant roles under the nitrogen and argon saturated
      conditions, while reaction in the supercritical interface decreased under the air
      and oxygen saturated conditions. Finally, LC-MS analysis was used to derive the
      by-products and propose the main pathways of DCF degradation by ultrasonic
      irradiation. 

PMID- 25065806
TI  - Disinfection of Bacillus spores with acidified nitrite.
AB  - Disinfecting water generated from a bioterrorism contamination event will require
      large amounts of disinfectant since the volume of water flushed from a drinking
      water distribution system or wash water collected from a contaminated outdoor
      area can accumulate quickly. Commonly used disinfectants may be unavailable in
      the necessary amounts, so evaluation of alternative disinfectants is needed. This
      study focuses on disinfection of Bacillus spores in water using acidified
      nitrite. The effect of varying pH (2 or 3), temperature (5 degrees C or 24
      degrees C), nitrite concentration (0.01 or 0.1M), buffer (Butterfields or
      Phosphate Buffered Saline, PBS) and Bacillus species (B. globigii and B.
      anthracis Sterne) was evaluated. B. globigii was more resistant to disinfection
      under all water quality conditions. Disinfection was more effective for B.
      globigii and B. anthracis Sterne at 0.1M nitrite, pH 2, and 24 degrees C.
      Disinfection of B. anthracis Sterne was enhanced in low ionic strength
      Butterfields buffer compared to PBS. 

PMID- 25065807
TI  - Biological and chemical phosphorus solubilization from pyrolytical biochar in
      aqueous solution.
AB  - Biochar, a massive byproduct of biomass pyrolysis during biofuel generation, is a
      potential P source for the mitigation of P depletion. However, the chemical and
      biological effect of the release of P from biochar is still unclear. In this
      study, two types of Lysinibacillus strains (Lysinibacillussphaericus D-8 and
      Lysinibacillus fusiformis A-5) were separated from a sediment and their P
      solubilizing characteristics to biochar was first reported. Compared with the
      bacterial mixture W-1 obtained from a bioreactor, the introduction of A-5 and D-8
      significantly improved P solubilization. The release of P from biochar by A-5 and
      D-8 reached 54% and 47%, respectively, which is comparable to that under rigorous
      chemical conditions. SEM images and XPS spectra demonstrated that the
      physicochemical properties of the biochar surface have changed in the process
      which may be caused by the activities of the microbes. 

PMID- 25065808
TI  - Effects of gas compositions on NOx reduction by selective non-catalytic reduction
      with ammonia in a simulated cement precalciner atmosphere.
AB  - The effects of gas compositions on NOx reduction and NH3 slip by selective non
      catalytic reduction (SNCR) with NH3 were investigated in a simulated cement
      precalciner atmosphere. The results show that the presence of H2O improves NOx
      reduction and widens the reduction temperature window significantly. O2 is
      indispensable for reducing NOx. The optimum reduction temperature decreases and
      the temperature window widens to a lower temperature with the increase of O2
      content. In addition, the increase of O2 content also results in a decrease of
      the maximum NOx reduction efficiency. The effect of SO2 on NOx reduction is
      negligible in the simulated precalciner atmosphere. To increase CO concentration
      makes NO reduction take place at relatively low temperatures. However, NH3 will
      tend to be oxidized into NO instead of reducing NO after entering the stream
      containing O2 at high temperatures if it is initially blended with a high
      concentration of CO in an oxygen-free environment. The increase of H2O, O2, SO2
      or CO concentration is helpful to reduce NH3 slip in the temperature region below
      900 degrees C. These effects are resulted from the fact that the generation and
      consumption of O and OH radicals which are crucial to NO reduction and formation
      can be influenced by the four gas compositions. In industrial operation of SNCR
      for cement precalciner, these effects should be taken into account to increase
      NOx reduction efficiency and avoid NH3 slip. 

PMID- 25065809
TI  - Antimicrobial activity of cobalt imidazolate metal-organic frameworks.
AB  - Two cobalt imidazolate metal-organic frameworks were evaluated as a bactericidal
      material against the growth of the Gram-negative bacteria Pseudomonas putida and
      Escherichia coli. Under the most unfavourable conditions, within the exponential
      growth phase and in the culture media for both microorganisms, the growth
      inhibition reached over 50% for concentrations of biocidal material in the 5
      10mgL(-1) range. The release of metal gives excellent durability with the
      antibacterial effect persisting after 3months. Both cobalt-based materials can be
      prepared with simple, cheap and easily accessible commercial ligands, leading to
      a more affordable possible future application as antimicrobial materials. 

PMID- 25065810
TI  - Anticipating the fate and impact of organic environmental contaminants: a new
      approach applied to the pharmaceutical furosemide.
AB  - The presence of trace levels of organic contaminants in the environment is
      currently an environmental concern. When these contaminants are subjected to
      environmental transformations, environmental transformation products (ETPs) are
      obtained, whose structures often remain unknown. The absence of information
      concerning these new compounds makes them unavailable and consequently makes
      their environmental detection as well as their (eco)toxicological study
      impossible. This report describes a multidisciplinary approach that seeks to both
      anticipate the fate and evaluate the impact of organic environmental
      contaminants. Our approach consists of three steps. First, isolated and fully
      characterized transformation products (TPs) of the parent molecule are obtained.
      In the second step, the parent molecule is subjected to environmentally relevant
      transformations to identify plausible ETPs. The detection of previously
      characterized TPs allows the concomitant identification of plausible ETPs. The
      third step is devoted to the toxicological evaluation of the identified plausible
      ETPs. Such an approach has recently been applied to furosemide and has allowed
      the identification of its main TPs. This report now seeks to identify and
      evaluate toxicologically plausible ETPs of this drug, which is also known as an
      environmental contaminant. 

PMID- 25065811
TI  - Propranolol: a novel treatment for angiolymphoid hyperplasia with eosinophilia.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic
      disease that manifests as dermal or subcutaneous red or brown papules or nodules,
      most commonly on the head and neck. Histologically, ALHE is characterized by
      vascular proliferation with epithelioid endothelial cells with surrounding
      lymphocytic and eosinophilic infiltrate. There may be an accompanying serum
      eosinophilia and local lymphadenopathy. We report a case of a 32-year-old woman
      who presented with multiple erythematous nodules in the periauricular area and
      the vertex of her scalp. The nodules had been present for several months.
      Surgical removal of one of the lesions confirmed the histological diagnosis of
      ALHE. The patient was started on oral propranolol (40 mg once daily) in an effort
      to reduce the vascular component of the lesions. Within 6 weeks, the patient
      noted that several of the lesions had decreased in size, and all were less
      erythematous. Propranolol was subsequently stopped within a few months of
      initiating treatment. One lesion recurred over a year later, and propranolol was
      then restarted. No new lesions occurred after 2 years of follow-up. 

PMID- 25065812
TI  - Enzymatic hydrolysis of esters containing a tetrazole ring.
AB  - The lipase-catalyzed enantioselective hydrolysis of acetates containing tetrazole
      moiety was studied. Among all tested lipases, Novozyme SP 435 allowed to obtain
      optically active 4-(5-aryl-2H-tetrazol-2yl)butan-2-ol and 1-(5-aryl-2H-tetrazol
      2yl)-propan-2-ol and their acetates with the highest optical purities (ee = 95%
      99%) and excellent enantioselectivity (E>100). Some of the synthesized tetrazole
      derivatives were screened for their antifungal activity. Racemic mixtures of 4-[5
      (4-chlorophenyl)-2H-tetrazol-2-yl)butan-2-ol as well as pure enantiomers of this
      compound showed promising antifungal activity against F. sambucinum, F.
      oxysporum, C. coccodes, and A. niger.

PMID- 25065813
TI  - First detection of co-circulation of West Nile and Usutu viruses in equids in the
      south-west of Tunisia.
AB  - In the last fifteen years, West Nile Virus (WNV) has dramatically expanded its
      geographic range and is now considered the most widespread arbovirus in the
      world. In Tunisia, West Nile Fever (WNF) outbreaks were reported in humans in
      1997, 2003 and 2012. Usutu Virus (USUV), which is a 'new' emerging Flavivirus
      antigenically close to WNV, has never been reported in Tunisia. A serological
      investigation in 284 equids was conducted in 2012 in the southern west region of
      the country to assess the presence and prevalence of the WNV and USUV infection.
      Of the 284 samples tested by competitive enzyme-linked immunoassay, 129 were
      positive. Of these, 120 (42.3%) had WNV-specific neutralizing antibodies. The
      prevalence was significantly higher in areas closer to the oasis compared with
      that of the surrounding arid areas. Antibody titres against USUV were also
      reported in 10 equids. This was the first evidence of USUV circulation in
      Tunisia. Data recorded by this study indicate that WNV and USUV have
      circulated/are circulating in the region and that there is an urgent need to
      adapt the current surveillance programmes to this new scenario. 

PMID- 25065814
TI  - Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained
      virological response.
AB  - In registration trials, triple therapy with telaprevir (TVR), pegylated
      interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response
      (SVR) rates between 64% and 75%, but the clinical effectiveness and economic
      burdens of this treatment in real-world practice remain to be determined. Records
      of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical
      Center (May-December 2011) were reviewed. Direct medical costs for pretreatment,
      on-treatment, and posttreatment care were calculated using data from Medicare
      reimbursement databases, RED Book, and the Healthcare Cost and Utilization
      Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable
      hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined
      on an intention-to-treat basis. Cost per SVR was calculated by dividing the
      median cost by the SVR rate. Median age of the 147 patients was 56 years
      (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human
      immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB
      4 scores >=3.25), and 44% achieved an SVR. The total cost of care was $11.56
      million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The
      median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR
      (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees
      (2%), and laboratory tests (1%). CONCLUSIONS: TVR and Peg-IFN accounted for 85%
      of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world
      study, were major contributors to the high cost per SVR.

PMID- 25065816
TI  - Pyodermatitis-pyostomatitis vegetans and antibullous pemphigoid antigen 180
      autoantibodies: a casual association?

PMID- 25065815
TI  - Effects of two different anesthetic protocols on 64-MDCT coronary angiography in
      dogs.
AB  - Heart rate is a major factor influencing diagnostic image quality in computed
      tomographic coronary artery angiography (MDCT-CA), with an ideal heart rate of 60
      65 beats/min in humans. The purpose of this prospective study was to compare
      effects of two different clinically applicable anesthetic protocols on
      cardiovascular parameters and 64-MDCT-CA quality in 10 healthy dogs. Scan
      protocols and bolus volumes were standardized. Image evaluations were performed
      in random order by a board-certified veterinary radiologist who was unaware of
      anesthetic protocols used. Heart rate during image acquisition did not differ
      between protocols (P = 1), with 80.6 +/- 7.5 bpm for protocol A and 79.2 +/- 14.2
      bpm for protocol B. Mean blood pressure was significantly higher (P > 0.05) using
      protocol B (protocol A 62.9 +/- 9.1 vs. protocol B 72.4 +/- 15.9 mmHg). The R-R
      intervals allowing for best depiction of individual coronary artery segments were
      found in the end diastolic period and varied between the 70% and 95% interval.
      Diagnostic quality was rated excellent, good, and moderate in the majority of the
      segments evaluated, with higher scores given for more proximal segments and lower
      for more distal segments, respectively. Blur was the most commonly observed
      artifact and mainly affected the distal segments. No significant differences were
      identified between the two protocols for optimal reconstruction interval,
      diagnostic quality and measured length individual segments, or proximal diameter
      of the coronary arteries (P = 1). Findings indicated that, when used with a
      standardized bolus volume, both of these anesthetic protocols yielded diagnostic
      quality coronary 64-MDCT-CA exams in healthy dogs. 

PMID- 25065817
TI  - The 2009 American Thyroid Association guidelines modestly reduced radioactive
      iodine use for thyroid cancers less than 1 cm.

PMID- 25065818
TI  - Optimizing the use of natural and synthetic magnetites with very small amounts of
      coarse Fe(0) particles for reduction of aqueous Cr(VI).
AB  - Remediation of highly toxic aqueous Cr(VI) includes its chemical reduction to the
      very insoluble Cr(III) species. In this work we investigated the Cr(VI) reduction
      performance of synthetic and natural magnetites of different particle size sat
      three pH values (4, 6, 8), with the purpose of cost-optimizing the procedure at
      the laboratory scale. Only the finest magnetite showed considerable Cr(VI)
      reduction yields, but rates were low and after 25 days no equilibrium was
      attained. Mechano chemical mixing of the finer magnetites with 5% micron-sized
      Fe(0) increased dramatically their reductive reactivity, especially at pH 4 and
      6, and at pH 8 only for the finest sample, despite the fact that the same
      quantity of Fe(0) added by itself reducednegligible amounts of Cr(VI). Increasing
      Fe(0) concentrations in the mixtures to 10 and 15% allowed considerable
      improvements in the reactivity of the intermediate-sized magnetites (of ca.
      7m(2)/g), but not that of the coarser samples for up to 20% Fe(0). This promises
      to be an optimal technology for remediation or treatment of Cr(VI) polluted
      aqueous environments and residues, that may prove beneficial for industries and
      pollution clean-up government agencies, because it uses readily available solid
      mineral samples and minimizes the use of acid reagents. 

PMID- 25065819
TI  - 'Reading the Mind in the Eyes': an fMRI study of adolescents with autism and
      their siblings.
AB  - BACKGROUND: Mentalizing deficits are a hallmark of the autism spectrum condition
      (ASC) and a potential endophenotype for atypical social cognition in ASC.
      Differences in performance and neural activation on the 'Reading the Mind in the
      Eyes' task (the Eyes task) have been identified in individuals with ASC in
      previous studies. METHOD: Performance on the Eyes task along with the associated
      neural activation was examined in adolescents with ASC (n = 50), their unaffected
      siblings (n = 40) and typically developing controls (n = 40). Based on prior
      literature that males and females with ASC display different cognitive and
      associated neural characteristics, analyses were stratified by sex. Three
      strategies were applied to test for endophenotypes at the level of neural
      activation: (1) identifying and locating conjunctions of ASC-control and sibling
      control differences; (2) examining whether the sibling group is comparable to the
      ASC or intermediate between the ASC and control groups; and (3) examining spatial
      overlaps between ASC-control and sibling-control differences across multiple
      thresholds. RESULTS: Impaired behavioural performance on the Eyes task was
      observed in males with ASC compared to controls, but only at trend level in
      females; and no difference in performance was identified between sibling and same
      sex control groups in both sexes. Neural activation showed a substantial
      endophenotype effect in the female groups but this was only modest in the male
      groups. CONCLUSIONS: Behavioural impairment on complex emotion recognition
      associated with mental state attribution is a phenotypic, rather than an
      endophenotypic, marker of ASC. However, the neural response during the Eyes task
      is a potential endophenotypic marker for ASC, particularly in females.

PMID- 25065820
TI  - Phosphate promotes uranium (VI) adsorption in Staphylococcus aureus LZ-01.
AB  - Staphylococcus aureus LZ-01 was isolated from the Yellow River upstream from
      Lanzhou which can resist and reduce chromium (VI) to chromium (III). In this
      study, strain LZ-01's uranium (VI) resistance and adsorption abilities were
      investigated. Our results showed that it can resist 2 mmol l(-1) U(VI) and adsorb
      96% of 2 mmol l(-1) U(VI) after 6 h incubation. Transmission electron microscopy
      (TEM) images showed that precipitates were formed on the surface of the cells.
      Energy dispersive X-ray spectroscopy (EDX) analysis indicated that the
      precipitates contained uranium and phosphorus. The U(VI) adsorption rate of
      strain LZ-01 was promoted by 20 mmol l(-1) phosphate. It adsorbed 45% of 2.5 mmol
      l(-1) U(VI) in 30 min compared to 36% without phosphate (P < 0.05). Strain LZ-01
      can resist heavy metals and survive in nuclear waste-contaminated environments.
      Strain LZ-01 might be a potential candidate for nuclear waste remediation with
      phosphate added. SIGNIFICANCE AND IMPACT OF THE STUDY: Staphylococcus aureus LZ
      01 can resist 2 mmol l(-1) U(VI). It could adsorb more than 90% of the 2 mmol l(
      1) U(VI) in 6 h. Uranium is precipitated with phosphorus on the surface of the
      cells. Phosphate promotes uranium adsorption in strain LZ-01, and its U(VI)
      adsorption capacity is related to its cell availability. These results indicate
      that the strain LZ-01 might be a potential candidate for remediation of nuclear
      waste when phosphate is added.

PMID- 25065822
TI  - Novel pipette-tip graphene/poly (vinyl alcohol) cryogel composite extractor for
      the analysis of carbofuran and carbaryl in water.
AB  - A novel pipette-tip extractor of a graphene/poly (vinyl alcohol) cryogel
      (graphene/PVA) composite sorbent was prepared to preconcentrate carbamate
      pesticides in environmental water samples before analysis with a gas
      chromatograph-flame ionization detector (GC-FID). This novel pipette-tip
      extractor with the graphene/PVA sorbent exhibited a high porosity when observed
      through a scanning electron micrograph (SEM). Under optimal conditions, using
      only 1.0 mL of sample and 0.75 mL of eluting solvent, the developed method
      provided a wide linear range of 10-700 ng mL(-1) and 10-500 ng mL(-1) with limit
      of detection (LOD) of 6.40 +/- 0.18 and 9.17 +/- 0.34 ng mL(-1) for carbofuran
      (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) and carbaryl (1
      naphthyl methylcarbamate), respectively. The pipette-tip extractor provided high
      extraction efficiency with high accuracy indicated, by good recoveries in the
      range of 74.5 +/- 4.8% to 119.7 +/- 1.6% and 76 +/- 15% to 114 +/- 19% for
      carbofuran and carbaryl, respectively. In addition, the fabrication procedure
      showed a good pipette-tip extractor-to-pipette-tip extractor reproducibility with
      a relative standard deviation of 1.3-9.8% (n = 5). When the developed pipette-tip
      extractor was applied for the extraction of carbofuran and carbaryl in surface
      water samples near vegetable plantation areas, 25.9 +/- 8.2 ng mL(-1) of
      carbofuran was found, and carbaryl was also detected in concentrations that
      ranged from 45.0 +/- 4.0 to 191 +/- 13 ng mL(-1).

PMID- 25065821
TI  - Orthogonal functionalisation of alpha-helix mimetics.
AB  - alpha-Helix mediated protein-protein interactions are of major therapeutic
      importance. As such, the design of inhibitors of this class of interaction is of
      significant interest. We present methodology to modify N-alkylated aromatic
      oligoamide alpha-helix mimetics using 'click' chemistry. The effect is shown to
      modulate the binding properties of a series of selective p53/hDM2 inhibitors. 

PMID- 25065823
TI  - Simultaneous voltammetric determination of four triazine herbicides in water
      samples with the aid of chemometrics.
AB  - A novel differential pulse voltammetry (DPV) method was developed for the
      simultaneous analysis of herbicides in water. A mixture of four herbicides,
      atrazine, simazine, propazine and terbuthylazine was analyzed simultaneously and
      the complex, overlapping DPV voltammograms were resolved by several chemometrics
      methods such as partial least squares (PLS), principal component regression (PCR)
      and principal component-artificial networks (PC-ANN). The complex profiles of the
      voltammograms collected from a synthetic set of samples were best resolved with
      the use of the PC-ANN method, and the best predictions of the concentrations of
      the analytes were obtained with the PC-ANN model (%RPET = 6.1 and average
      %Recovery = 99.0). The new method was also used for analysis of real samples, and
      the obtained results were compared well with those from the GC-MS technique. Such
      conclusions suggest that the novel method is a viable alternative to the other
      commonly used methods such as GC, HPLC and GC-MS. 

PMID- 25065824
TI  - Application of various methods to determine the lipophilicity parameters of the
      selected urea pesticides as predictors of their bioaccumulation.
AB  - Different lipophilicity procedures including a newly developed (based on Oscik's
      equation) was applied in order to compare various urea pesticides with herbicidal
      and also insecticidal activity, such as monolinuron, chlorotoluron, diuron,
      isoproturon, linuron, dimefuron, diflubenzuron, teflubenzuron and lufenuron.
      Lipophilicity parameters (RMWS and RMW0) of nine examined pesticides were
      determined on the chromatographic plates RP-8F254 with the use of methanol-water
      as a mobile phase. Similarity analysis enabled to group all examined pesticides
      depending on their lipophilic character and allowed to perform a more objective
      comparison of different lipophilicity parameters obtained for investigated
      compounds by means of thin-layer chromatography and by the use of computational
      methods. It was stated that with the number of fluorine in examined pesticides,
      the lipophilic character of insecticides and also their tendency to
      bioaccumulation in the living systems increases noticeably. The results of this
      work confirmed that a new procedure for determining the lipophilicity parameter
      (RMW0) by Oscik's equation could be a suitable tool in the prediction of
      pesticide bioaccumulation in living system and may be used as an indicator in
      design of new urea pesticides, which will be safe for humans and the environment.

PMID- 25065825
TI  - Environmental behavior of benalaxyl and furalaxyl enantiomers in agricultural
      soils.
AB  - The enantioselective environmental behavior of the chiral fungicides benalaxy and
      furalaxyl in agricultural soils in China was studied. Although sorption onto
      soils was non-enantioselective, the leaching of benalaxy and furalaxyl was
      enantioselective in soil columns. The concentrations of the S-enantiomers of both
      fungicides in the leachates were higher than the R-enantiomers. This can be
      attributed to enantioselective degradation of the two fungicides in the soil
      column. Enantioselective degradation of the two fungicides was verified by soil
      dissipation experiments, and the R-enantiomers degraded faster than the S
      enantiomers in partial soils. The half-life was 27.7-57.8 days for S-benalaxyl,
      20.4-53.3 days for R-benalaxyl, 19.3-49.5 days for S-furalaxyl and 11.4-34.7 days
      for R-furalaxyl. The degradation process of the two fungicide enantiomers
      followed the first-order kinetics (R(2) > 0.96). Compared to furalaxyl, benalaxyl
      degraded more slowly and degradation was less enantioselective. These results are
      attributed to the influence of soil physicochemical properties, soil
      microorganisms, and environmental factors.

PMID- 25065826
TI  - Influence of the pesticides glyphosate, chlorpyrifos and atrazine on growth
      parameters of nonochratoxigenic Aspergillus section Nigri strains isolated from
      agricultural soils.
AB  - This investigation was undertake to determine the effect of glyphosate,
      chlorpyrifos and atrazine on the lag phase and growth rate of nonochratoxigenic
      A. niger aggregate strains growing on soil extract medium at -0.70, -2.78 and 
      7.06 MPa. Under certain conditions, the glyphosate concentrations used
      significantly increased micelial growth as compared to control. An increase of
      about 30% was observed for strain AN 251 using 5 and 20 mg L(-1) of glyphosate at
      -2.78 MPa. The strains behaved differently in the presence of the insecticide
      chlorpyrifos. A significant decrease in growth rate, compared to control, was
      observed for all strains except AN 251 at -2.78 MPa with 5 mg L(-1). This strain
      showed a significant increase in growth rate. With regard to atrazine,
      significant differences were observed only under some conditions compared to
      control. An increase in growth rate was observed for strain AN 251 at -2.78 MPa
      with 5 and 10 mg L(-1) of atrazine. By comparison, a reduction of 25% in growth
      rate was observed at -7.06 MPa and higher atrazine concentrations. This study
      shows that glyphosate, chlorpyrifos and atrazine affect the growth parameters of
      nonochratoxigenic A. niger aggregate strains under in vitro conditions.

PMID- 25065827
TI  - Changes in TcpA gene frequency explain 2,4,6-trichlorophenol degradation in
      mesocosms.
AB  - Soils are often polluted by chlorophenols in timber production areas in the
      northern hemisphere. The tcpA gene encodes the first step of 2,4,6
      trichlorophenol (246-TCP) degradation. We tested tcpA gene frequency in three
      natural pristine soils with different 246-TCP degradation capacity. Gene tcpA
      frequency increased more in spiked than non-spiked 10-L pails containing
      coniferous humus soil with high degradation capacity, in contrast to soils where
      degradation was slower. As the soil in each mesocosm originated from a spatially
      separate field plot, changes in tcpA gene frequency affected 246-TCP degradation
      over a range of soil origins. This indicates that the abundance of and changes in
      tcpA gene frequency could be utilized in estimating the efficacy of natural
      attenuation and biostimulation treatments in controlled conditions. 

PMID- 25065828
TI  - Lipophilic organic pollutants induce changes in phospholipid and membrane protein
      composition leading to Vero cell morphological change.
AB  - Membrane damage related to morphological change in Vero cells is a sensitive
      index of the composite biotoxicity of trace lipophilic chemicals. However,
      judging whether the morphological change in Vero cells happens and its ratio are
      difficult because it is not a quantitative characteristic. To find biomarkers of
      cell morphological change for quantitatively representing the ratio of
      morphological changed cell, the mechanism of cell membrane damage driven by
      typical lipophilic chemicals, such as trichlorophenol (TCP) and
      perfluorooctanesulphonate (PFOS), was explored. The ratio of morphologically
      changed cells generally increased with increased TCP or PFOS concentrations, and
      the level of four major components of phospholipids varied with concentrations of
      TCP or PFOS, but only the ratio of phosphatidylcholine
      (PC)/phosphatidylethanolamine (PE) decreased regularly as TCP or PFOS
      concentrations increased. Analysis of membrane proteins showed that the level of
      vimentin in normal cell membranes is high, while it decreases or vanishes after
      TCP exposure. These variations in phospholipid and membrane protein components
      may result in membrane leakage and variation in rigid structure, which leads to
      changes in cell morphology. Therefore, the ratio of PC/PE and amount of vimentin
      may be potential biomarkers for representing the ratio of morphological changed
      Vero cell introduced by trace lipophilic compounds, thus their composite bio
      toxicity. 

PMID- 25065829
TI  - Impact of soil management practices on yield, fruit quality, and antioxidant
      contents of pepper at four stages of fruit development.
AB  - Peppers, a significant component of the human diet in many regions of the world,
      provide vitamins A (beta-carotene) and C, and are also a source of many other
      antioxidants such as capsaicin, dihydrocapsaicin, and phenols. Enhancing the
      concentration of antioxidants in plants grown in soil amended with recycled waste
      has not been completely investigated. Changes in pepper antioxidant content in
      relation to soil amendments and fruit development were investigated. The main
      objectives of this investigation were to: (i) quantify concentrations of
      capsaicin, dihydrocapsaicin, beta-carotene, ascorbic acid, phenols, and soluble
      sugars in the fruits of Capsicum annuum L. (cv. Xcatic) grown under four soil
      management practices: yard waste (YW), sewage sludge (SS), chicken manure (CM),
      and no-much (NM) bare soil and (ii) monitor antioxidant concentrations in fruits
      of plants grown under these practices and during fruit ripening from green into
      red mature fruits. Total marketable pepper yield was increased by 34% and 15% in
      SS and CM treatments, respectively, compared to NM bare soil; whereas, the number
      of culls (fruits that fail to meet the requirements of foregoing grades) was
      lower in YW compared to SS and CM treatments. Regardless of fruit color, pepper
      fruits from YW amended soil contained the greatest concentrations of capsaicin
      and dihydrocapsaicin. When different colored pepper fruits (green, yellow,
      orange, and red) were analyzed, orange and red contained the greatest beta
      carotene and sugar contents; whereas, green fruits contained the greatest
      concentrations of total phenols and ascorbic acid. 

PMID- 25065830
TI  - Bioenergy production from diluted poultry manure and microbial consortium inside
      Anaerobic Sludge Bed Reactor at sub-mesophilic conditions.
AB  - In this study, anaerobic treatability of diluted chicken manure (with an influent
      feed ratio of 1 kg of fresh chicken manure to 6 L of tap water) was investigated
      in a lab-scale anaerobic sludge bed (ASB) reactor inoculated with granular seed
      sludge. The ASB reactor was operated at ambient temperature (17-25 degrees C) in
      order to avoid the need of external heating up to higher operating temperatures
      (e.g., up to 35 degrees C for mesophilic digestion). Since heat requirement for
      raising the temperature of incoming feed for digestion is eliminated, energy
      recovery from anaerobic treatment of chicken manure could be realized with less
      operating costs. Average biogas production rates were calculated ca. 210 and 242
      L per kg of organic matter removed from the ASB reactor at average hydraulic
      retention times (HRTs) of 13 and 8.6 days, respectively. Moreover, average
      chemical oxygen demand (COD) removal of ca. 89% was observed with suspended
      solids removal more than 97% from the effluent of the ASB reactor. Influent
      ammonia, on the other hand, did not indicate any free ammonia inhibition due to
      dilution of the raw manure while pH and alkalinity results showed stability
      during the study. Microbial quantification results indicated that as the number
      of bacterial community decreased, the amount of Archaea increased through the
      effective digestion volume of the ASB reactor. Moreover, the number of
      methanogens displayed an uptrend like archaeal community and a strong correlation
      (-0.645) was found between methanogenic community and volatile fatty acid (VFA)
      concentration especially acetate.

PMID- 25065831
TI  - Low-heat alkaline pretreatment of biomass for dairy anaerobic codigestion.
AB  - In this research, low-heat alkaline pretreatment was evaluated to determine the
      extent to which urban landscape waste (yard waste), corn stover, and switchgrass
      could be codigested under conditions typical of US farm-based anaerobic digestion
      (AD). Waste heat from combined heat and power (CHP) units associated with AD
      could make such pretreatment economical. Short-term batch digestion studies and 8
      week continuous-feed studies were used to screen and evaluate various
      pretreatment conditions. Results indicate that maple and oak leaves did not
      digest well, even with pretreatment. Pretreatment did improve digestion of corn
      leaves and stalks as well as switchgrass. However, these materials also digested
      reasonably well even without pretreatment. No digester operational problems were
      observed during continuous-feed studies of intermittently stirred bench top
      digesters, but optimal levels of alkali, temperature, and pretreatment time may
      be specific to the feedstock, particle size, and digester loading rate. Results
      suggest that some common lignocellulosic biomass materials, such as corn stover
      and switchgrass, could be successfully codigested in many existing farm-based
      digesters. Interestingly, without pretreatment, switchgrass digestion improved
      over 20-fold when digested with seed culture from a dairy digester compared to
      seed culture from a municipal digester, suggesting that culture acclimation could
      be as important as pretreatment in improving digestion of specific
      lignocellulosic feedstocks. 

PMID- 25065832
TI  - Involvement of MU- and delta-opioid receptor function in the rewarding effect of
      (+/-)-pentazocine.
AB  - Most opioid receptor agonists have abuse potential, and the rewarding effects of
      opioids can be reduced in the presence of pain. While each of the enantiomers of
      pentazocine has a differential pharmacologic profile, (+/-)-pentazocine has been
      used clinically for the treatment of pain. However, little information is
      available regarding which components of pentazocine are associated with its
      rewarding effects, and whether the (+/-)-pentazocine-induced rewarding effects
      can be suppressed under pain. Therefore, the present study was performed to
      investigate the effects of pain on the acquisition of the rewarding effects of
      (+/-)-pentazocine, and to examine the mechanism of the rewarding effects of (+/-)
      pentazocine using the conditioned place preference paradigm. (+/-)-Pentazocine
      and (-)-pentazocine, but not (+)-pentazocine, produced significant rewarding
      effects. Even though the rewarding effects induced by (+/-)-pentazocine were
      significantly suppressed under pain induced by formalin, accompanied by increase
      of preprodynorphin mRNA levels in the nucleus accumbens, a high dose of (+/-)
      pentazocine produced significant rewarding effects under pain. In the normal
      condition, (+/-)-pentazocine-induced rewarding effects were blocked by a low dose
      of naloxone, whereas the rewarding effects induced by high doses of pentazocine
      under pain were suppressed by naltrindole (a delta-opioid receptor antagonist).
      Interestingly, (+/-)-pentazocine did not significantly affect dopamine levels in
      the nucleus accumbens. These findings suggest that the rewarding effects of (-)
      pentazocine may contribute to the abuse potential of (+/-)-pentazocine through MU
      as well as delta-opioid receptors, without robust activation of the mesolimbic
      dopaminergic system. We also found that neural adaptations can reduce the abuse
      potential of (+/-)-pentazocine under pain. 

PMID- 25065833
TI  - Optimizing clinical competency committee work through taking advantage of overlap
      across milestones.

PMID- 25065834
TI  - Influences on visit retention in clinical trials: insights from qualitative
      research during the VOICE trial in Johannesburg, South Africa.
AB  - BACKGROUND: Although significant progress has been made in clinical trials of
      women-controlled methods of HIV prevention such as microbicides and Pre-exposure
      Prophylaxis (PrEP), low adherence to experimental study products remains a major
      obstacle to being able to establish their efficacy in preventing HIV infection.
      One factor that influences adherence is the ability of trial participants to
      attend regular clinic visits at which trial products are dispensed, adherence
      counseling is administered, and participant safety is monitored. We conducted a
      qualitative study of the social contextual factors that influenced adherence in
      the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study
      participation in general, and study visits in particular. METHODS: The research
      used qualitative methodologies, including in-depth interviews (IDI), serial
      ethnographic interviews (EI), and focus group discussions (FGD) among a random
      sub-sample of 102 female trial participants, 18 to 40 years of age. A socio
      ecological framework that explored those factors that shaped trial participation
      and adherence to study products, guided the analysis. Key codes were developed to
      standardize subsequent coding and a node search was used to identify texts
      relating to obstacles to visit adherence. Our analysis includes coded transcripts
      from seven FGD (N = 40), 41 IDI, and 64 serial EI (N = 21 women). RESULTS:
      Women's kinship, social, and economic roles shaped their ability to participate
      in the clinical trial. Although participants expressed strong commitments to
      attend study visits, clinic visit schedules and lengthy waiting times interfered
      with their multiple obligations as care givers, wage earners, housekeepers, and
      students. CONCLUSIONS: The research findings highlight the importance of the
      social context in shaping participation in HIV prevention trials, beyond focusing
      solely on individual characteristics. This points to the need to focus
      interventions to improve visit attendance by promoting a culture of active and
      engaged participation.

PMID- 25065835
TI  - Orthodontic treatment for a patient with hereditary angiodema: a case report.
AB  - BACKGROUND: Hereditary angiodema (HAE), also known as C1 esterase inhibitor
      deficiency, causes sufferers to experience episodic subcutaneous and submucosal
      oedema. These episodes can be triggered by dental treatment and manifest as life
      threatening oedematous swelling in the head and neck region. CASE REPORT: This
      case report reviews an adolescent with hereditary angiodema whose malocclusion
      required orthodontic intervention. Due to her complex and unpredictable reaction
      to dental treatment, various options were explored before determining the
      appropriate care pathway for this patient. Trial placement of a sectional fixed
      appliance tested the tissue reaction prior to comprehensive treatment including
      extractions and fixed orthodontic appliances. CONCLUSION: This report
      demonstrates successful interdisciplinary management facilitating orthodontic
      care in a patient with HAE.

PMID- 25065836
TI  - Milk quality control: instant and quantitative milk fat determination with a
      BODIPY sensor-based fluorescence detector.
AB  - The first fluorescent sensor for milk fat was developed. It exhibited a
      magnificent, yet selective turn-on feature towards fat molecules in a complicated
      milk matrix by a disaggregation-induced emission mechanism. Further construction
      of a handy fluorescence milk fat detector provided a convenient rapid tool to
      measure the fat amount quantitatively. This discovery may help enhance the milk
      quality control process. 

PMID- 25065837
TI  - Maximizing the electromagnetic and chemical resonances of surface-enhanced Raman
      scattering for nucleic acids.
AB  - Although surface-enhanced Raman spectroscopy (SERS) has previously been performed
      with nucleic acids, the measured intensities for each nucleic acid have varied
      significantly depending on the SERS substrate and excitation wavelength. We have
      demonstrated that the charge-transfer (CT) mechanism, also known as the chemical
      enhancement of SERS, is responsible for the discrepancies previously reported in
      literature. The electronic states of cytosine and guanine attached to silver
      atoms are computationally calculated and experimentally measured to be in the
      visible range, which leads to a resonance Raman effect at the corresponding
      maximum wavelengths. The resulting SERS measurements are in good agreement with
      the simulated values, in which cytosine-silver shows stronger enhancement at 532
      nm and guanine-silver shows stronger enhancement at 785 nm. An atomic layer of
      aluminum oxide is deposited on substrates to prevent charge-transfer, and
      corresponding measurements show weaker Raman signals caused by the suppression of
      the chemical resonance. These findings suggest the optimal SERS signal can be
      achieved by tuning the excitation wavelength to match both the electromagnetic
      and chemical resonances, paving the way for future single molecule detection of
      nucleic acids other than adenine. 

PMID- 25065838
TI  - The effects of age and past and present behavioral specialization on behavior of
      workers of the red wood ant Formica polyctena Forst. during nestmate reunion
      tests.
AB  - Social insect workers usually participate first in intranidal tasks and then
      switch to extranidal ones. However, foragers may switch again to intranidal brood
      care. This process is called the behavioral reversion. We applied dyadic nestmate
      reunion tests to explore behavioral differences between five groups of workers of
      the red wood ant Formica polyctena: callows (newly eclosed workers), nurses,
      reverted nurses (foragers that switched back to intranidal brood care in response
      to exposure to brood in absence of nurses), and two groups of foragers. Inter
      group differences between the tested ants were related both to age and past and
      present behavioral specialization. Callows were the least active and their
      behavior was characterized by the lowest tempo. Nurses usually behaved in a way
      intermediate in respect to behavior of callows and the ants that had already
      passed the transition to extranidal tasks. The behavior of reverted nurses showed
      both similarities and differences with respect to behavior of foragers. Some
      traits of behavior of reverted nurses were similar as in the case of nurses, or
      intermediate in respect to both nurses and foragers. Behavioral reversion of
      workers of F. polyctena has thus other behavioral correlates besides the
      reappearance of intranidal brood care. 

PMID- 25065839
TI  - Characterization of a human epidermis model reconstructed from hair follicle
      keratinocytes and comparison with two commercially models and native skin.
AB  - OBJECTIVE: Outer root sheath (ORS) cells of human hair follicles are a readily
      available, non-invasive source of keratinocytes for epidermis reconstruction. The
      aim of this study was to characterize a model of epidermis reconstructed from ORS
      cells (ORS-derived model) and to evaluate its reproducibility, in comparison with
      native human skin and two marketed reconstructed skin models (model A,
      Episkin((r)) and model B, Skinethic((r)) ). METHODS: Cell morphology and tissue
      architecture of the three models were analysed histologically and proliferation
      and differentiation marker expression by immunohistochemistry and mRNA
      quantification. RESULTS: All models displayed the same general epidermal
      architecture as native epidermis, but with a thicker stratum corneum in models A
      and B. Compared with native epidermis, Ki67 was correctly localized in epidermal
      basal cells in all models, as K10 in suprabasal layers. In all skin models,
      transglutaminase 1 (TGM1) was prematurely expressed in suprabasal layers.
      However, this expression was only observed from the upper stratum spinosum in the
      ORS-derived model. In this model, filaggrin and loricrin were correctly located
      in the stratum granulosum. Filaggrin, involucrin, loricrin and TGM1 mRNAs
      (markers of keratinocyte terminal differentiation) were transcriptionally
      expressed in all models. In the ORS-derived model, transcriptional expression
      level was similar to that of native skin. CONCLUSION: ORS cell-based
      reconstructed epidermis is a valid and reproducible model for human epidermis and
      it may be used to evaluate the effects of active substances and cosmetic
      formulations.

PMID- 25065840
TI  - Quality lung cancer screening protects quality of life: no harm, no foul.

PMID- 25065841
TI  - One-pot self-templating synthesis of Pt hollow nanostructures and their catalytic
      properties for CO oxidation.
AB  - Nanoporous Pt hollow nanostructures with octahedral and hexagonal frame-like
      morphologies were prepared by a novel one-pot self-templating route with no
      assistance from a preformed template or shape-directing agent. The hexagonal
      frame-like Pt hollow structures exhibited significantly enhanced catalytic
      activity toward CO oxidation reaction compared to the octahedral Pt hollow
      nanostructures due to the higher oxidation state of Pt. 

PMID- 25065842
TI  - Miller Fisher syndrome related to Orientia tsutsugamushi infection.
AB  - Miller Fisher syndrome is typically associated with a preceding infection,
      especially with Campylobacter jejuni. We describe a patient with Miller Fisher
      syndrome following Orientia tsutsugamushi infection, which to our knowledge has
      not been previously reported. 

PMID- 25065843
TI  - A 10 year retrospective study of surgical outcomes of adult intracranial
      pilocytic astrocytoma.
AB  - Pilocytic astrocytomas (PA) are benign neoplasms commonly located in the
      cerebellum with a peak incidence in the first two decades of life. PA occurrence
      in adults is rare and very little information is available in the literature
      about tumour characteristics in this population. This study retrospectively
      identified 20 adults with PA. The characteristics of the tumour, treatment
      modalities and patient outcomes are discussed, as well as identifying factors
      that may be associated with worse prognosis. The mean age at diagnosis was 27
      years. The majority of PA were located in the posterior fossa. Other tumour
      locations included the cerebral hemispheres, brainstem, tectal plate and
      optochiasmatic region (optic chiasm, hypothalamus and third ventricle). All
      patients in this study underwent surgery, two received adjuvant chemotherapy and
      one received adjuvant radiotherapy. Tumour recurrence occurred in six patients
      and two eventually died from the disease. When achieved, complete tumour
      resection was found to be curative. Tumour location affects extent of surgical
      resection; tumours in inaccessible locations were associated with higher rates of
      recurrence. Overall survival and progression free survival rates were 87% and 60%
      respectively. The degree of surgical resection and tumour location were found to
      affect prognosis. Unfavourable outcomes were observed in these adults with PA
      compared to those expected for a younger population, suggesting a possible
      association between age and outcome.

PMID- 25065844
TI  - Diurnal salivary cortisol measurement in the neurosurgical-surgical intensive
      care unit in critically ill acute trauma patients.
AB  - Acute trauma patients represent a specific subgroup of the critically ill
      population due to sudden and dramatic changes in homeostasis and consequently
      extreme demands on the activity of the hypothalamic-pituitary-adrenocortical
      (HPA) axis. Salivary cortisol is an accepted surrogate for serum free cortisol in
      the assessment of HPA axis function. The purpose of this study was (1) to
      establish the feasibility of salivary cortisol measurement in acute trauma
      patients in the neurosurgical-surgical intensive care unit (NSICU), and (2) to
      determine the diurnal pattern of salivary cortisol in the acute phase after
      injury. Saliva from 50 acute trauma patients was prospectively collected twice a
      day at 6AM and 4PM during the first week after injury in the NSICU. Mean PM
      cortisol concentrations were significantly higher in subjects versus controls
      (p<0.001). Subjects failed to develop the expected PM versus AM decrease in
      cortisol concentration seen in controls (p=0.005). Salivary cortisol did not vary
      significantly with baseline Glasgow Coma Scale (GCS), Injury Severity Score, sex,
      injury type, ethnicity, or age. When comparing mean AM and PM salivary cortisol
      by GCS severity category (GCS ?8 and GCS >8) the AM salivary cortisol was
      significantly higher in patients with GCS ?8 (p=0.002). The results show a loss
      of diurnal cortisol variation in acute trauma patient in the NSICU during the
      first week of hospitalization. Patients with severe brain injury had higher
      morning cortisol levels than those with mild/moderate brain injury. 

PMID- 25065845
TI  - Phosphorylated neurofilament subunit NF-H becomes elevated in the cerebrospinal
      fluid of patients with acutely worsening symptoms of compression myelopathy.
AB  - It is known that the severity of compression myelopathy sometimes worsens rapidly
      and results in poor functional recovery because of limited axonal regeneration.
      Levels of phosphorylated neurofilament subunit NF-H (pNF-H), which indicate
      axonal degeneration, are elevated in other neurological disorders. To our
      knowledge, there has been no examination of pNF-H levels in compression
      myelopathy. Therefore, we conducted a pilot cross-sectional study to evaluate pNF
      H levels in the cerebrospinal fluid (CSF) of patients with worsening symptoms of
      cervical compression myelopathy. From January 2011 to March 2013, 51 samples of
      CSF were collected from patients at the time of myelography before spinal
      surgery. The indications for surgery were acutely worsening compression
      myelopathy (AM) in eight, chronic compression myelopathy (CM) in six, and lumbar
      canal stenosis (LCS) in 37 patients. The pNF-H levels were measured using a
      standard enzyme-linked immunosorbent assay. The mean +/- standard deviation pNF-H
      value was 2127.1 +/- 556.8 pg/ml in AM patients, 175.8 +/- 67.38 pg/ml in CM
      patients and 518.7 +/- 665.7 pg/ml in LCS patients. A significant increase in pNF
      H levels was detected in the CSF of patients with AM compared with those with
      either CM or LCS. The clinical outcome of surgical treatment for patients with
      cervical myelopathy was satisfactory in both AM and CM patients. Despite the
      limitations of small sample size and lack of healthy CSF control data due to
      ethical considerations, our results suggest that pNF-H in CSF can act as a
      biomarker that reflects the severity of AM.

PMID- 25065846
TI  - Clinical characteristics of 92 patients with temporal lobe focal cortical
      dysplasia identified by pathological examination.
AB  - Focal cortical dysplasia (FCD) is frequently associated with focal epilepsy, and
      a broad spectrum of histopathology is included in the diagnosis of FCD. In 2011,
      an International League Against Epilepsy (ILAE) task force proposed an
      international consensus for a classification system to better characterise
      specific clinicopathological FCD entities. The clinical characteristics of
      patients with FCD should be confirmed according to the new ILAE classification.
      We retrospectively analysed 92 patients who had undergone surgical treatment for
      temporal lobe epilepsy and received a pathological diagnosis of FCD. The
      pathological sections were re-examined and diagnosed according to the 2011 ILAE
      classification. The clinical data from patients with different FCD subtypes were
      evaluated, including a detailed history regarding spontaneous abortions, trauma,
      ischaemic injury, encephalitis, and febrile seizures at an early age. The age of
      epilepsy onset, duration of epilepsy, age at surgery, seizure frequency, history
      of febrile seizures, and seizure type, particularly whether the seizures were
      secondarily generalised tonic-clonic seizures, were recorded. Clinical
      differences were found in the patients with temporal lobe FCD. The associated FCD
      subtypes have unique clinical characteristics, including a later age of epilepsy
      onset and a shorter duration of epilepsy, especially in FCD Type IIIc; and a high
      susceptibility to febrile seizures was observed in FCD Type IIIa. 

PMID- 25065847
TI  - Concurrent neoadjuvant chemotherapy is an independent risk factor of stroke, all
      cause morbidity, and mortality in patients undergoing brain tumor resection.
AB  - Neoadjuvant chemotherapy (NC) may be utilized for treatment of various tumors,
      and a proportion of patients on active NC may require resection of a primary or
      secondary brain tumor. The objective of this study is to examine the impact of NC
      on postoperative neurosurgical outcomes. Elective cranial neurosurgical patient
      data was obtained from the American College of Surgeons National Surgical Quality
      Improvement Program database between 2006 and 2012. The impact of NC on 30 day
      stroke, all-cause postoperative morbidity, and mortality were assessed. Adjusted
      odds ratios (OR) were estimated for stroke, overall morbidity, and mortality
      using a multivariable logistic regression model, accomplished in stepwise
      fashion, for patients receiving NC versus those not receiving NC. This study
      analyzed 3812 patients undergoing elective cranial surgery, with 152 on
      concurrent NC. NC patients had a complication rate of 23.68%, while patients not
      receiving NC had a lower complication rate at 17.65% (p=0.057). Multivariable
      regression analysis revealed that patients who received NC had significantly
      increased odds of developing a stroke with neurological deficit (OR 3.39; 95%
      confidence interval [CI] 1.37-8.40) and all-cause postoperative morbidity (OR
      1.57; 95% CI 1.04-2.37) over the control group. Finally, the NC cohort
      demonstrated higher odds of mortality following surgery than their non-NC
      counterparts (OR 3.81; 95% CI 1.81-8.02). Ninety-two patients (2.41%) died within
      30 days, of whom 10 (6.58%) were receiving NC versus 82 non-NC (2.24%) patients
      (p=0.001). Concurrent NC is associated with an increased risk of short-term
      stroke with neurological deficit, all-cause morbidity, and mortality in patients
      undergoing brain tumor resection.

PMID- 25065848
TI  - Growth hormone treatment and risk of recurrence or development of secondary
      neoplasms in survivors of pediatric brain tumors.
AB  - Growth hormone (GH) is increasingly used for treatment of pediatric brain tumors.
      However, controversy remains over its safety. This meta-analysis assessed whether
      GH treatment was associated with risk of recurrence or development of secondary
      neoplasm for brain tumors in children. Systematic computerized searches of PubMed
      and Web of Knowledge were performed. Pooled relative risks (RR) with 95%
      confidence interval (CI) for recurrence and/or secondary neoplasm in children who
      were treated with GH versus those who did not receive GH were calculated. Ten
      studies were included. The pooled recurrence rates were 21.0% and 44.3% in the GH
      treated group and non-GH-treated group, respectively. The pooled RR for
      recurrence was 0.470 (95% CI 0.372-0.593; z=6.33, p=0.000). Begg's test (p=0.060)
      and Egger's test (p=0.089) suggested there was no significant publication bias.
      The pooled RR in sensitivity analysis was 0.54 (95% CI 0.37-0.77; z=3.32,
      p=0.001), which showed the result was robust. The pooled RR for secondary
      neoplasm was 1.838 (95% CI 1.053-3.209; z=2.14, p=0.032). Begg's test (p=1.000)
      and Egger's test (p=0.553) suggested there was no significant publication bias.
      We found no evidence that GH therapy is associated with an increased risk of
      recurrence for pediatric brain tumors. However, because of our small sample size,
      the association of GH therapy with an increased risk of secondary neoplasm is
      uncertain. Further prospective cohorts are needed. 

PMID- 25065849
TI  - Spinal metastasis of gliosarcoma: array-based comparative genomic hybridization
      for confirmation of metastatic spread.
AB  - We report a 64-year-old woman who underwent craniotomy and gross total resection
      of a left frontal lobe tumor initially diagnosed as glioblastoma. Multiple wound
      revisions were necessary due to repeated wound healing disorders under
      concomitant radio-chemotherapy. After 9 months there was local cranial tumor
      recurrence, requiring re-operation. Thereafter, temozolomide monotherapy was
      implemented. Histologically, a shift from glial to mesenchymal differentiation
      was observed in the recurrent tumor, resulting in the diagnosis of gliosarcoma. A
      further 9 months later a thoracic spinal tumor occurred requiring emergency tumor
      resection. Analysis showed a mesenchymal tumor without definite glial component.
      Being resistant to local radiation therapy, symptomatic local spinal tumor
      progression was observed within 1 month requiring re-resection. There was no
      response to chemotherapy with bevacizumab and irinotecan. Considering the
      pronounced sarcoma-like differentiation, a sarcoma chemotherapy regime with
      doxorubicin was initiated. This was also to no avail; the disease progressed and
      recurred at both the spinal and cerebral locations, respectively. This ambiguous
      tumor characteristic and therapy resistance encouraged us to retrospectively
      perform molecular and array-based comparative genomic hybridization (aCGH)
      analysis on the extirpated cerebral and spinal tumors. Tumors from both locations
      showed a consistent cytogenetic signature of gain of chromosome 7, and losses of
      chromosomes 10 and 13. This novel report of aCGH analysis of spinal gliosarcoma
      metastasis and the correlation to the clinical disease course shows that
      genotypic profiling may serve as a supplementary diagnostic tool in improving our
      knowledge of the biologic behavior of rare tumor variants.

PMID- 25065850
TI  - Gamma Knife radiosurgery following subtotal resection of vestibular schwannoma.
AB  - During treatment of large vestibular schwannomas, incomplete resection (IR)
      followed by Gamma Knife surgery (GKS; Elekta AB, Stockholm, Sweden) possibly
      offers tumor growth control and good clinical outcome, and is being discussed as
      an alternative to complete tumor removal with its inherent risks, especially for
      facial nerve function. However, available data for this concept are limited due
      to the small number of published studies. To analyze the effects of combined
      therapy in a larger cohort, we reviewed the currently available data. Six studies
      comprising 159 patients with a tumor diameter of at least 2 cm were included
      (median volume 19.95 cm(3) in four studies, n=137). GKS was performed on average
      6 months postoperatively with a mean marginal dose of 11.88 Gy (mean target
      volume 4.42 cm(3), mean diameter 18.45 mm). Preoperatively facial nerve function
      was serviceable (House and Brackmann Grades I+II) in 158 of 159 patients (99.4%)
      and in 125 of 151 patients (82.8%, 95% confidence interval [CI] 76-88%)
      postoperatively. Hearing was serviceable in 29 of 151 patients (19.2%)
      preoperatively and in 16 of 79 patients postoperatively (20.2%, 95%CI 12-31%).
      Within a mean follow-up time of 50 months (range 12-102 months), facial nerve
      function and hearing after IR remained serviceable in 142 of 151 (94.0%, 95%CI 89
      97%) and 15 of 129 patients (11.6%, 95%CI 7-18%). Tumor growth control was
      achieved in 149 of 159 patients (93.8%). Six patients were subjected to repeated
      therapy. Minimal complications were reported for microsurgery and GKS. Combined
      therapy was shown to be beneficial regarding both tumor control and adverse side
      effects among all analyzed studies.

PMID- 25065851
TI  - An examination of the postmortem redistribution of fentanyl and interlaboratory
      variability.
AB  - Fentanyl is a synthetic opioid agonist used for pain control. Often administered
      as a transdermal patch, it is an interesting drug for study of postmortem
      redistribution. We hypothesized that fentanyl concentrations would increase over
      time after death, as measured in blood drawn on the day prior to autopsy and in
      blood drawn at the time of autopsy in ten cases where fentanyl patches were
      identified at the scene. Concentrations were compared, and heart blood to femoral
      blood ratios were calculated as markers of postmortem redistribution. Fentanyl
      concentrations measured in peripheral blood drawn the day of autopsy (peripheral
      blood 2 [PB2]) were higher than those drawn the day prior to autopsy (peripheral
      blood 1 [PB1]) with a mean ratio (PB2/PB1) of 1.80. The ratio of heart blood
      concentrations (HB) to femoral blood concentrations drawn at autopsy (PB2) had a
      mean ratio (HB/PB2) of 1.08. Some cases had blood from the same source analyzed
      at two different laboratories, and concentrations of fentanyl in those samples
      showed inter- and intralaboratory differences up to 25 ng/mL. Postmortem fentanyl
      concentrations may be affected by antemortem factors, postmortem redistribution,
      and laboratory variability. Forensic pathologists must use caution in
      interpreting fentanyl levels as part of death investigation. 

PMID- 25065852
TI  - Ultrastructure and complex polar architecture of the human pathogen Campylobacter
      jejuni.
AB  - Campylobacter jejuni is one of the most successful food-borne human pathogens.
      Here we use electron cryotomography to explore the ultrastructure of C. jejuni
      cells in logarithmically growing cultures. This provides the first look at this
      pathogen in a near-native state at macromolecular resolution (~5 nm). We find a
      surprisingly complex polar architecture that includes ribosome exclusion zones,
      polyphosphate storage granules, extensive collar-shaped chemoreceptor arrays, and
      elaborate flagellar motors. 

PMID- 25065853
TI  - Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer
      cells.
AB  - Pathway-targeted cancer drugs can produce dramatic responses that are invariably
      limited by the emergence of drug-resistant cells. We found that many drug-treated
      "oncogene-addicted" cancer cells engage a positive feedback loop leading to Stat3
      activation, consequently promoting cell survival and limiting overall drug
      response. This was observed in cancer cells driven by diverse activated kinases,
      including EGFR, HER2, ALK, and MET, as well as mutant KRAS. Specifically, MEK
      inhibition led to autocrine activation of Stat3 via the FGF receptor and JAK
      kinases, and pharmacological inhibition of MEK together with JAK and FGFR
      enhanced tumor regression. These findings suggest that inhibition of a Stat3
      feedback loop may augment the response to a broad spectrum of drugs that target
      pathways of oncogene addiction. 

PMID- 25065854
TI  - A novel HBA2 gene conversion in cis or trans: "alpha12 allele" in a Saudi
      population.
AB  - Thalassemia and sickle cell disease are the most prevalent hemoglobin disorders
      in the populations of Dammam, Al-Qatif and Al-Ahsa regions in the Eastern
      Province of Saudi Arabia where our study cases originated. Increased HbF can
      modify these disorders. Direct sequencing of the HBA2 and HBA1 genes from 157
      Saudi subjects revealed a new HBA2 gene conversion in cis or trans in 5.7% of the
      total. We refer to this new HBA2 gene convert as an alpha12 (HBA12) allele due to
      its combination of alpha1 (HBA1) and alpha2 (HBA2) sequences. Three genotypes,
      homozygous (-alpha12(3.7)/alpha1alpha12), heterozygous
      (alpha1alpha2/alpha1alpha12) and hemizygous (alpha1- (4.2)/alpha1alpha12) for the
      alpha12 allele were observed. The majority of individuals who were positive for
      the alpha12 allele had a reduction in the percentage of HbA2. Further studies are
      necessary to evaluate the possible effect of these changes on globin gene
      expression. 

PMID- 25065855
TI  - A prospective randomized wait list control trial of intravenous iron sucrose in
      older adults with unexplained anemia and serum ferritin 20-200 ng/mL.
AB  - Anemia is common in older persons and is associated with substantial morbidity
      and mortality. One third of anemic older adults have unexplained anemia of the
      elderly (UAE). We carried out a randomized, wait list control trial in
      outpatients with UAE and serum ferritin levels between 20 and 200 ng/mL.
      Intravenous iron sucrose was given as a 200-mg weekly dose for 5 weeks either
      immediately after enrollment (immediate intervention group) or following a 12
      week wait list period (wait list control group). The primary outcome measure was
      changed in 6-minute walk test (6MWT) distances from baseline to 12 weeks between
      the two groups. Hematologic, physical, cognitive, and quality of life parameters
      were also assessed. The study was terminated early after 19 subjects enrolled.
      The distance walked in the 6MWT increased a mean 8.05+/-55.48 m in the immediate
      intervention group and decreased a mean 11.45+/-49.46 m in the wait list control
      group (p=0.443). The hemoglobin increased a mean 0.39+/-0.46 g/dL in the
      immediate intervention group and declined a mean 0.39+/-0.85 g/dL in the wait
      list control group (p=0.026). Thus, a subgroup of adults with UAE may respond to
      intravenous iron. Enrollment of subjects into this type of study remains
      challenging.

PMID- 25065856
TI  - Growth differentiation factor-15 in young sickle cell disease patients: relation
      to hemolysis, iron overload and vascular complications.
AB  - BACKGROUND: High expression of growth differentiation factor-15 (GDF-15)
      contributes to pathological iron overload in thalassemia. Sickle cell syndromes
      are characterized by increased levels of erythropoiesis, although the primary
      defect involves the destruction of mature erythrocytes. AIM: To determine serum
      GDF-15 in 35 children and adolescents with sickle cell disease (SCD) compared to
      35 healthy controls and assess its relation to markers of hemolysis, iron
      overload and vascular complications. METHODS: GDF-15 was measured and correlated
      to genotype, frequency of sickling crises, hydroxyurea therapy and serum
      ferritin. RESULTS: GDF-15 levels were increased in SCD patients whether sickle
      cell anemia or sickle beta degrees  thalassemia compared with controls (p<0.001)
      with no significant difference between patients' groups. GDF-15 was significantly
      higher in patients who had serum ferritin >=2500 MUg/L, previous cerebral stroke,
      and splenectomy. GDF-15 was not significantly related to frequency of sickling
      crises, pulmonary hypertension, or hydroxyurea therapy. On regression analysis,
      transfusion index, lactate dehydrogenase and serum ferritin were independently
      related to GDF-15. CONCLUSION: Increased GDF-15 in SCD reflects the importance of
      ineffective erythropoiesis in the pathophysiology and severity of anemia in SCD.
      GDF-15 levels are related to hemolysis and iron overload and may provide utility
      for identifying patients at increased risk of thrombotic events.

PMID- 25065858
TI  - Moving HIV PrEP from research into practice.

PMID- 25065857
TI  - Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men
      and transgender women who have sex with men: a cohort study.
AB  - BACKGROUND: The effect of HIV pre-exposure prophylaxis (PrEP) depends on uptake,
      adherence, and sexual practices. We aimed to assess these factors in a cohort of
      HIV-negative people at risk of infection. METHODS: In our cohort study, men and
      transgender women who have sex with men previously enrolled in PrEP trials (ATN
      082, iPrEx, and US Safety Study) were enrolled in a 72 week open-label extension.
      We measured drug concentrations in plasma and dried blood spots in seroconverters
      and a random sample of seronegative participants. We assessed PrEP uptake,
      adherence, sexual practices, and HIV incidence. Statistical methods included
      Poisson models, comparison of proportions, and generalised estimating equations.
      FINDINGS: We enrolled 1603 HIV-negative people, of whom 1225 (76%) received PrEP.
      Uptake was higher among those reporting condomless receptive anal intercourse
      (416/519 [81%] vs 809/1084 [75%], p=0.003) and having serological evidence of
      herpes (612/791 [77%] vs 613/812 [75%] p=0.03). Of those receiving PrEP, HIV
      incidence was 1.8 infections per 100 person-years, compared with 2.6 infections
      per 100 person-years in those who concurrently did not choose PrEP (HR 0.51, 95%
      CI 0.26-1.01, adjusted for sexual behaviours), and 3.9 infections per 100 person
      years in the placebo group of the previous randomised phase (HR 0.49, 95% CI 0.31
      0.77). Among those receiving PrEP, HIV incidence was 4.7 infections per 100
      person-years if drug was not detected in dried blood spots, 2.3 infections per
      100 person-years if drug concentrations suggested use of fewer than two tablets
      per week, 0.6 per 100 person-years for use of two to three tablets per week, and
      0.0 per 100 person-years for use of four or more tablets per week (p<0.0001).
      PrEP drug concentrations were higher among people of older age, with more
      schooling, who reported non-condom receptive anal intercourse, who had more
      sexual partners, and who had a history of syphilis or herpes. INTERPRETATION:
      PrEP uptake was high when made available free of charge by experienced providers.
      The effect of PrEP is increased by greater uptake and adherence during periods of
      higher risk. Drug concentrations in dried blood spots are strongly correlated
      with protective benefit. FUNDING: US National Institutes of Health.

PMID- 25065859
TI  - Brain grey matter abnormalities in medication-free patients with major depressive
      disorder: a meta-analysis.
AB  - BACKGROUND: Because cerebral morphological abnormalities in major depressive
      disorder (MDD) may be modulated by antidepressant treatment, inclusion of
      medicated patients may have biased previous meta-analyses of voxel-based
      morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD
      patients should be able to distinguish the morphological features of the disease
      itself from those of treatment. METHOD: A systematic search was conducted for the
      relevant studies. Effect-size signed differential mapping was applied to analyse
      the grey matter differences between all medication-free MDD patients and healthy
      controls. Meta-regression was used to explore the effects of demographics and
      clinical characteristics. RESULTS: A total of 14 datasets comprising 400
      medication-free MDD patients and 424 healthy controls met the inclusion criteria.
      The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey
      matter in prefrontal and limbic regions in MDD. Increased right thalamus volume
      was only seen in first-episode medication-naive patients, and increased grey
      matter in the bilateral anterior cingulate cortex only in medication wash-out
      patients. In meta-regression analyses the percentage of female patients in each
      study was negatively correlated with reduced grey matter in the right
      hippocampus. CONCLUSIONS: By excluding interference from medication effects, the
      present study identified grey matter reduction in the prefrontal-limbic network
      in MDD. The subgroup meta-analysis results suggest that an increased right
      thalamus volume might be a trait directly related to MDD, while an increased
      anterior cingulate cortex volume might be an effect of medication. The meta
      regression results perhaps reveal the structural underpinning of the sex
      differences in epidemiological and clinical aspects of MDD.

PMID- 25065860
TI  - Coronary vasospasm during CT angiography.
AB  - A 71-year-old man, a heavy smoker, was admitted for evaluation of "chest
      oppression" after every dinner. Cardiac CT with a beta-blocker showed coronary
      stenosis in the left circumflex. Although adenosine triphosphate-stress perfusion
      single-photon emission CT revealed no ischemia, Holter electrocardiography
      belatedly indicated an ST elevation associated with his symptoms while smoking.
      He was diagnosed to have vasospastic angina. Cardiac CT without a beta-blocker
      showed thin diffuse plaque and negative remolding without any significant
      stenosis at the same site. Asian patients have a tendency to develop vasospastic
      angina. Although beta-blockers are recommended for cardiac CT, the routine
      administration of beta-blockers in cardiac CT may have some risk for such cases.

PMID- 25065862
TI  - Reprint of PSII manganese cluster: protonation of W2, O5, O4 and His337 in the S1
      state explored by combined quantum chemical and electrostatic energy
      computations.
AB  - Photosystem II (PSII) is a membrane-bound protein complex that oxidizes water to
      produce energized protons, which are used to built up a proton gradient across
      the thylakoidal membrane in the leafs of plants. This light-driven reaction is
      catalyzed by withdrawing electrons from the Mn4CaO5-cluster (Mn-cluster) in four
      discrete oxidation steps [S1-(S4/S0)] characterized in the Kok-cycle. In order to
      understand in detail the proton release events and the subsequent translocation
      of such energized protons, the protonation pattern of the Mn-cluster need to be
      elucidated. The new high-resolution PSII crystal structure from Umena, Kawakami,
      Shen, and Kamiya is an excellent basis to make progress in solving this problem.
      Following our previous work on oxidation and protonation states of the Mn
      cluster, in this work, quantum chemical/electrostatic calculations were performed
      in order to estimate the pKa of different protons of relevant groups and atoms of
      the Mn-cluster such as W2, O4, O5 and His337. In broad agreement with previous
      experimental and theoretical work, our data suggest that W2 and His337 are likely
      to be in hydroxyl and neutral form, respectively, O5 and O4 to be unprotonated.
      This article is part of a special issue entitled: photosynthesis research for
      sustainability: keys to produce clean energy.

PMID- 25065861
TI  - Longitudinal epigenetic variation of DNA methyltransferase genes is associated
      with vulnerability to post-traumatic stress disorder.
AB  - BACKGROUND: Epigenetic differences exist between trauma-exposed individuals with
      and without post-traumatic stress disorder (PTSD). It is unclear whether these
      epigenetic differences pre-exist, or arise following, trauma and PTSD onset.
      METHOD: In pre- and post-trauma samples from a subset of Detroit Neighborhood
      Health Study participants, DNA methylation (DNAm) was measured at DNA
      methyltransferase 1 (DNMT1), DNMT3A, DNMT3B and DNMT3L. Pre-trauma DNAm
      differences and changes in DNAm from pre- to post-trauma were assessed between
      and within PTSD cases (n = 30) and age-, gender- and trauma exposure-matched
      controls (n = 30). Pre-trauma DNAm was tested for association with post-trauma
      symptom severity (PTSS) change. Potential functional consequences of DNAm
      differences were explored via bioinformatic search for putative transcription
      factor binding sites (TFBS). RESULTS: DNMT1 DNAm increased following trauma in
      PTSD cases (p = 0.001), but not controls (p = 0.067). DNMT3A and DNMT3B DNAm
      increased following trauma in both cases (DNMT3A: p = 0.009; DNMT3B: p < 0.001)
      and controls (DNMT3A: p = 0.002; DNMT3B: p < 0.001). In cases only, pre-trauma
      DNAm was lower at a DNMT3B CpG site that overlaps with a TFBS involved in
      epigenetic regulation (p = 0.001); lower pre-trauma DNMT3B DNAm at this site was
      predictive of worsening of PTSS post-trauma (p = 0.034). Some effects were
      attenuated following correction for multiple hypothesis testing. CONCLUSIONS:
      DNAm among trauma-exposed individuals shows both longitudinal changes and pre
      existing epigenetic states that differentiate individuals who are resilient
      versus susceptible to PTSD. These distinctive DNAm differences within DNMT loci
      may contribute to genome-wide epigenetic profiles of PTSD.

PMID- 25065863
TI  - Why men and women might not be so different.

PMID- 25065864
TI  - [Mechanism for bone metastasis].
AB  - Cancer cells in the bone metastasis would acquire their characteristic malignant
      potentials by breaking through the struggle for existence in the various
      metastasis steps, all of which are required for the cancer cells in the bone
      microenvironment to emerge as clinical bone metastasis. We have demonstrated that
      receptor activator of NF-kappaB ligand (RANKL) was involved in the tumor-stromal
      interaction in the bone microenvironment and TGFbeta stored in the bone matrix
      was released with the bone destruction, which promoted the proliferation of
      cancer cells in the bone. We also demonstrated that epigenetics, which is the
      transcriptional regulatory mechanism without gene mutation, was involved in the
      acquisition of drug resistance in the cancer cells. We believe that the
      mechanisms for bone metastasis formation would be fully elucidated in the near
      future, and the molecular-targeted therapies, which was developed based on these
      findings, would relief the patients from the fear of death. 

PMID- 25065865
TI  - [Strategy of therapy for bone metastases of cancer].
AB  - Recently, the importance of cancer-induced bone disease has been recognized. Bone
      metastases of cancer usually do not have major impacts on prognosis of patients,
      but skeletal-related events (SRE) markedly aggravate QOL of patients. For bone
      metastases, multi-disciplinary approaches including drug therapy, orthopedic
      therapy, radiation therapy, or intervention therapy are necessary. As drug
      therapy, bone-specific drugs that inhibit osteoclasts such as bisphosphonates,
      anti-RANKL antibody denosumab have been developed and have shown to decrease SRE
      and improve QOL. Further development of new bone-specific drugs is ongoing. 

PMID- 25065866
TI  - [Derangements of mineral metabolism associated with tumors].
AB  - Bone as a hard tissue has several functions such as supporting our body and
      protecting internal organs. In addition, bone has a pivotal role in the
      regulation of circulatory mineral concentrations. Therefore, abnormal bone
      metabolism is sometimes accompanied by deranged serum calcium or phosphate levels
      as shown in patients with malignancy-associated hypercalcemia (MAH) or tumor
      induced osteomalacia (TIO) . Parathyroid hormone-related protein, PTHrP, was
      cloned as a major humoral factor causing MAH. Similarly, fibroblast growth factor
      23, FGF23, was identified as a causative factor for TIO. Therefore, MAH and TIO
      are not only important in clinical practice but also gave us deep insights into
      the mechanisms of mineral homeostasis, and bone and cartilage metabolism. 

PMID- 25065867
TI  - [Myeloma bone disease].
AB  - Multiple myeloma (MM) develops and expands almost exclusively in the bone marrow,
      and generates devastating bone destruction. MM cells produce a variety of
      cytokines to stimulate RANK ligand-mediated osteoclastogenesis and suppress
      osteoblastic differentiation from bone marrow stromal cells, leading to extensive
      bone destruction with rapid loss of bone. Pim-2 kinase as well as growth factor
      independence-1 (Gfi-1) were found to be up-regulated in bone marrow stromal cells
      by major inhibitors of bone formation known in myeloma as common downstream
      mediators for the suppression of osteoblastogenesis. The biology of osteocytes is
      largely unknown in myeloma bone lesions, but the reduction of viable osteocytes
      and their correlation with osteoclastogenesis have been demonstrated. 

PMID- 25065868
TI  - [Bone metastasis from prostate cancer].
AB  - Bone metastases are often observed in patients with lung cancer, kidney cancer,
      breast cancer, myeloma, and prostate cancer. Bone metastases from prostate cancer
      often show characteristics different from those that originated from other organs
      : For instance, bone is often the only target organ for prostate cancer
      metastases, and bone metastatic lesions from prostate cancer are more
      osteoblastic than osteolytic. It is thought that metastatic prostate cancer cells
      interact specifically with osseous tissue and that this tissue-specific
      interaction is a critical factor in cancer progression. An understanding of bone
      metastasis in prostate cancer may lead to novel treatments against the disease.
      Here, we present the mechanisms that underlie osteoblastic bone metastasis of
      prostatic origin. 

PMID- 25065869
TI  - [Bone metastases of breast cancer].
AB  - Bone is one of the most preferential metastatic target sites for cancers. The
      biological crosstalk between metastatic cancer cells and bone microenvironment is
      critical to the pathophysiology of bone metastases. For example, It is well
      established that PTH-rP production in cancer cells stimulated by bone-derived TGF
      beta facilitates bone metastasis through promoting bone resorption by
      osteoclasts, thereby establishing "vicious cycle" between metastatic cancer cells
      and bone. In addition, recent studies identified several new players including
      platelets and MDSCs which contribute to the development of bone metastasis. In
      this review, we will overview the current topics on the mechanism by which bone
      metastasis is modulated at cellular and molecular levels.

PMID- 25065870
TI  - [Molecular mechanisms of bone cancer pain].
AB  - Bone pain is one of the most frequent complications of bone metastasis, leading
      to a marked reduction in the quality of life of patients. The mechanisms of bone
      cancer pain are highly complicated ; however, noxious stimuli produced by cancer
      tissues and cancer-induced nerve injury are considered to be the major causes.
      Recent studies also suggest the possible involvement of acidic microenvironments
      created by cancer tissues and osteoclasts in cancer-induced bone pain.
      Understanding the molecular events may lead to the design of novel mechanism
      based approaches for the management of bone pain associated with cancer
      metastasis. 

PMID- 25065871
TI  - [Vitamin D and cancer].
AB  - Vitamin D acts through vitamin D receptor, expressed in a variety of human
      tissues, including cancer tissues of various origins. Basic research has a
      revealed vitamin D has anti-cancer potentials including pro-differentiation, anti
      proliferation, anti-inflammation, anti-angiogenesis and many other effects.
      Epidemiological studies have revealed that low serum 25 (OH) D level, i.e.
      vitamin D deficiency/insufficiency, is associated with higher incidence in colon
      cancer. Low serum 25 (OH) D level in colon or breast cancer patients is
      associated with poor prognosis. Despite these results, clinical studies so far
      have not demonstrated any effects of vitamin D supplementation on cancer
      incidence or prognosis. Many large randomized controlled studies are in-progress
      now about the effects of vitamin D supplementation on cancer. Their results are
      anticipated. 

PMID- 25065872
TI  - [Bone metastasis and RANKL].
AB  - The mice with a disruption of Rank or Rankl exhibit normal mammary development
      during puberty, but their mammary epithelium fails to proliferate and form
      lobuloalveolar structures during pregnancy, resulting in the death of newborns.
      Hormone replacement therapy is associated with an increased risk of breast
      cancer. Importantly, specific deletion of RANK in mammary epithelium cells
      prevents both the onset and progression of medroxyprogesterone acetate (MPA) 
      driven mammary cancer and impairs self-renewal of breast cancer stem cells.
      Furthermore, RANK is highly expressed in several cancer cells. Functionally, it
      has been shown that RANKL can stimulate the directed migration of mammary
      epithelial cells as well as prostate cancer and melanoma cells toward a source of
      RANKL. In an in vivo metastasis model, OPG reduced the tumor burden in bones and
      ameliorated clinical paralysis, but did not affect the frequency of the spread of
      metastases into other tissues. These findings show that the RANK/RANKL system is
      crucial for mammary development, breast tumorigenesis and bone metastasis. 

PMID- 25065873
TI  - [Regulation of bone metastasis by microRNAs].
AB  - Bone metastasis is a common complication in patients with advanced cancer. It can
      increase the risk of severe pain, pathological fracture, and spinal cord
      compression, which make physical activity remarkably worse. Identification of the
      molecular mechanisms in the initiation or progression of bone metastasis and
      development of novel therapeutic approaches are very important. microRNAs
      (miRNAs) have been known as key players in cancer initiation or cancer
      progression. Recently, the importance of miRNAs in regulating bone metastasis has
      been also appreciated. Further understanding of the role of miRNAs in metastatic
      bone disease will lead to the development of novel diagnostic or therapeutic
      approaches to bone metastasis. 

PMID- 25065874
TI  - [Anti-FGF23 antibody therapy for patients with tumor-induced osteomalacia].
AB  - Tumor-induced osteomalacia (TIO) is a disease caused by fibroblast growth factor
      23 (FGF23) secreted from the causative tumor. This disease is cured by complete
      surgical removal of the tumor. However, there are several difficult cases in
      which the responsible tumors cannot be found, are incompletely removed, or
      relapse after the surgery. Anti-FGF23 antibody is being studied as a novel
      therapy for FGF23-related hypophosphatemic diseases. The efficacy of anti-FGF23
      antibodies were confirmed using a murine model of X-linked hypophosphatemic
      rickets (XLHR) , which is the most common heritable form of FGF23-related
      hypophosphatemic disease. In addition, results of phase I study of single
      injection of humanized anti-FGF23 antibody for adult patients with XLHR were
      recently published and the safety and effectiveness of this antibody was shown.
      This antibody therapy may be useful for patients with TIO with similar
      pathogenesis to that of XLHR. 

PMID- 25065875
TI  - [Treatment of malignancy associated hypercalcemia].
AB  - Malignancy associated hypercalcemia (MAH) is a paraneoplastic syndrome that
      impairs the quality of life and that can be a direct cause of death. MAH is
      classified into two major categories : humoral hypercalcemia of malignancy (HHM)
      and local osteolytic hypercalcemia (LOH) . Bisphosphonates are the gold standard
      of treatment for MAH, because enhanced resorption causing a massive calcium
      mobilization from bone plays a central role in the pathogenesis of MAH.
      Calcitonin can be used initially as an adjunctive therapy, because it takes a few
      days for bisphosphonates to be effective. Saline infusion is also necessary to
      improve dehydration and renal insufficiency inevitably accompanying MAH. 

PMID- 25065876
TI  - [The treatment for cancer with bone metastases -whether to use zoledoronate or
      denosumab for bone metastases-].
AB  - Osteoclast activation is a fundamental role in developing bone metastases. The
      treatment of any cancers with bone metastases has been changing due to emergence
      of bisphosphonates. Bisphosphonate reduces the occurrence of skeletal-related
      events (SREs ; pathological fractures, spinal cord compression, bone pain
      requiring palliative radiotherapy, hypercalcemia and orthopaedic surgery) by
      inhibiting the osteoclast function which affects improvement of daily life.
      Within the Bisphosphonate zoledoronate is the most effective agent in terms of
      reducing SREs. Denosumab is a fully human monoclonal antibody that binds to human
      receptor activator of nuclear factor kappa-B ligand (RANKL) , that blocks the
      formation of osteoclast and inhibiting osteoclast-mediated bone destruction.
      Denosumab was superior to zoledonate in terms of prevention of SREs. But,
      denosumab was similar to zoledronic acid for quality of life, pain and overall
      survival. On the other hand bisphosphonate has diverse anti-tumor effects and
      many trials showed beneficial to survival when it used for breast cancer in an
      adjuvant setting especially low estradiol circumstances. Radionuclides are
      another treatment option for bone pain. New targeted therapies and radionuclides
      are promising option for treatment of bone metastases but still under
      investigation. This article will focus on medical treatment for bone metastases
      especially from breast cancer.

PMID- 25065877
TI  - Preparation and studies of chiral stationary phases containing enantiopure
      acridino-18-crown-6 ether selectors.
AB  - The enantiomeric separation ability of the newly prepared chiral stationary
      phases containing acridino-18-crown-6 ether selectors was studied by high
      performance liquid chromatography (HPLC). The chiral stationary phases separated
      the enantiomers of selected protonated primary aralkylamines efficiently. The
      best results were found for the separation of the mixtures of enantiomers of NO2 
      PEA.

PMID- 25065878
TI  - Posttransfusion purpura occurrence and potential risk factors among the inpatient
      US elderly, as recorded in large Medicare databases during 2011 through 2012.
AB  - BACKGROUND: Posttransfusion purpura (PTP) is a serious transfusion complication
      resulting in sudden thrombocytopenia with bleeding. The study's objective was to
      assess PTP occurrence and potential risk factors among the inpatient US elderly,
      ages 65 and older, during 2011 through 2012. STUDY DESIGN AND METHODS: This
      retrospective claims-based study utilized large Medicare databases for calendar
      years 2011 and 2012. Transfusions of blood and blood components were identified
      by recorded ICD-9-CM procedure codes and revenue center codes, and PTP was
      ascertained via ICD-9-CM diagnosis code. Our study evaluated PTP rates (per
      100,000 inpatient transfusion stays) among elderly Medicare beneficiaries,
      overall and by age, sex, race, number of units, and blood components transfused.
      Multivariate regression analyses were used to assess potential risk factors.
      RESULTS: Among 4,336,338 inpatient transfusion stays for elderly beneficiaries
      during the study period, 78 had a PTP diagnosis code recorded, an overall rate of
      1.8 per 100,000 stays. PTP occurrence varied by the blood components, units
      transfused, and other characteristics. Significantly higher odds of PTP were
      found for platelet (PLT)-containing transfusions, with greater number of units
      transfused, as well as for elderly with histories of cardiac arrhythmias (odds
      ratio [OR], 2.65; 95% confidence interval [CI], 1.43-4.93), coagulopathy (OR,
      1.79; 95% CI, 1.01-3.21), leukemia (OR, 2.37; 95% CI, 1.07-5.26), transplant (OR,
      2.68; 95% CI, 1.41-5.09), and other conditions. CONCLUSION: Our population-based
      study suggests a substantially higher PTP risk with PLT-containing transfusions.
      The study also suggests increased PTP risk with greater number of units
      transfused as well as the importance of underlying health conditions and prior
      recipient alloimmunization for PTP occurrence among the elderly.

PMID- 25065879
TI  - Differential thermodynamic driving force of first- and second-generation
      antihistamines to determine their binding affinity for human H1 receptors.
AB  - Differential binding sites for first- and second-generation antihistamines were
      indicated on the basis of the crystal structure of human histamine H1 receptors.
      In this study, we evaluated differences between the thermodynamic driving forces
      of first- and second-generation antihistamines for human H1 receptors and their
      structural determinants. The binding enthalpy and entropy of 20 antihistamines
      were estimated with the van't Hoff equation using their dissociation constants
      obtained from their displacement curves against the binding of [(3)H]mepyramine
      to membrane preparations of Chinese hamster ovary cells expressing human H1
      receptors at various temperatures from 4 degrees C to 37 degrees C. Structural
      determinants of antihistamines for their thermodynamic binding properties were
      assessed by quantitative structure-activity relationship (QSAR) analyses. We
      found that entropy-dependent binding was more evident in second- than first
      generation antihistamines, resulting in enthalpy-entropy compensation between the
      binding forces of first- and second-generation antihistamines. QSAR analyses
      indicated that enthalpy-entropy compensation was determined by the sum of
      degrees, maximal electrostatic potentials, water-accessible surface area and
      hydrogen binding acceptor count of antihistamines to regulate their affinity for
      receptors. In conclusion, it was revealed that entropy-dependent hydrophobic
      interaction was more important in the binding of second-generation
      antihistamines, even though the hydrophilicity of second-generation
      antihistamines is generally increased. Furthermore, their structural determinants
      responsible for enthalpy-entropy compensation were explored by QSAR analyses.
      These findings may contribute to understanding the fundamental mechanisms of how
      the affinity of ligands for their receptors is regulated. 

PMID- 25065881
TI  - Combining aromaticity and strain with Tetsuo Nozoe--a passage of time with
      friends.
AB  - Note from the Editor: Tetsuo Nozoe lived his entire life on one of several island
      nations (Japan and Formosa, subsequently Taiwan, then returning to Japan). Those
      of us--and that is most of us!--who have never lived on an island nation likely
      cannot completely appreciate the 'isolation' and 'lack of diversity' that
      accompanies--along with many other valuable and happy consequences--such a life
      experience. As a New Zealander, colloquially as a Kiwi, Brian Halton shares this
      life experience with Nozoe. Indeed, New Zealand is far more isolated than either
      Japan or Taiwan in terms of distance to its nearest neighbor, population density,
      and size of its chemical community. Often during his career, Halton travelled to
      foreign lands, as did Nozoe, to fill his cup with collegiality and science. And
      Halton welcomed visitors to his beautiful country, as did Nozoe. Indeed, their
      mutual friendship was a blessing and honor to each of them. As Brian Halton tells
      his story of place and of science, I can well imagine Tetsuo Nozoe's response if
      he could read these words. He surely would have beamed in understanding these
      shared experiences!--Jeffrey I. Seeman Guest Editor University of Richmond
      Richmond, Virginia 23173, USA E-mail: jseeman@richmond.edu.

PMID- 25065880
TI  - GABAB receptor phosphorylation regulates KCTD12-induced K+ current
      desensitization.
AB  - GABAB receptors assemble from GABAB1 and GABAB2 subunits. GABAB2 additionally
      associates with auxiliary KCTD subunits (named after their K(+) channel
      tetramerization-domain). GABAB receptors couple to heterotrimeric G-proteins and
      activate inwardly-rectifying K(+) channels through the betagamma subunits
      released from the G-protein. Receptor-activated K(+) currents desensitize in the
      sustained presence of agonist to avoid excessive effects on neuronal activity.
      Desensitization of K(+) currents integrates distinct mechanistic underpinnings.
      GABAB receptor activity reduces protein kinase-A activity, which reduces
      phosphorylation of serine-892 in GABAB2 and promotes receptor degradation. This
      form of desensitization operates on the time scale of several minutes to hours. A
      faster form of desensitization is induced by the auxiliary subunit KCTD12, which
      interferes with channel activation by binding to the G-protein betagamma
      subunits. Here we show that the two mechanisms of desensitization influence each
      other. Serine-892 phosphorylation in heterologous cells rearranges KCTD12 at the
      receptor and slows KCTD12-induced desensitization. Likewise, protein kinase-A
      activation in hippocampal neurons slows fast desensitization of GABAB receptor
      activated K(+) currents while protein kinase-A inhibition accelerates fast
      desensitization. Protein kinase-A fails to regulate fast desensitization in
      KCTD12 knock-out mice or knock-in mice with a serine-892 to alanine mutation,
      thus demonstrating that serine-892 phosphorylation regulates KCTD12-induced
      desensitization in vivo. Fast current desensitization is accelerated in
      hippocampal neurons carrying the serine-892 to alanine mutation, showing that
      tonic serine-892 phosphorylation normally limits KCTD12-induced desensitization.
      Tonic serine-892 phosphorylation is in turn promoted by assembly of receptors
      with KCTD12. This cross-regulation of serine-892 phosphorylation and KCTD12
      activity sharpens the response during repeated receptor activation. 

PMID- 25065882
TI  - Health service delivery models for the provision of antiretroviral therapy in sub
      Saharan Africa: a systematic review.
AB  - OBJECTIVES: In response to the lack of evidence-based guidance for how to
      continue scaling up antiretroviral therapy (ART) in ways that make optimal use of
      limited resources, to assess comparative studies of ART service delivery models
      implemented in sub-Saharan Africa. METHODS: A systematic literature search and
      analysis of studies that compared two or more methods of ART service delivery
      using either CD4 count or viral load as a primary outcome. RESULTS: Most studies
      identified in this review were small and non-randomised, with low statistical
      power. Four of the 30 articles identified by this review conclude that nurse
      management of ART compares favourably to physician management. Seven provide
      evidence of the viability of managing ART at lower levels within the health
      system, and one indicates that vertical and integrated ART programmes can achieve
      similar outcomes. Five articles show that community/home-based ART management can
      be as effective as facility-based ART management. Five of seven articles
      investigating community support link it to better clinical outcomes. The results
      of four studies suggest that directly observed therapy may not be an important
      component of ART programmes. CONCLUSIONS: Given that the scale-up of
      antiretroviral therapy represents the most sweeping change in healthcare delivery
      in sub-Saharan Africa in recent years, it is surprising to not find more evidence
      from comparative studies to inform implementation strategies. The studies
      reported on a wide range of service delivery models, making it difficult to draw
      conclusions about some models. The strongest evidence was related to the
      feasibility of decentralisation and task-shifting, both of which appear to be
      effective strategies.

PMID- 25065883
TI  - Transdermal delivery of angiotensin II receptor blockers (ARBs), angiotensin
      converting enzyme inhibitors (ACEIs) and others for management of hypertension.
AB  - CONTEXT: Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme
      inhibitors (ACEIs) are some of the most commonly prescribed medications for
      hypertension. OBJECTIVE: Most of all conventional dosage forms of ARBs and ACEIs
      undergo extensive first-pass metabolism, which significantly reduces
      bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a
      rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs
      have many high incidences of adverse effects due to variable absorption profiles,
      higher frequency of administration and poor patient compliance. METHODS: Many
      attempts have been made globally at the laboratory level to investigate the skin
      permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs
      and other anti-hypertensives, to circumvent the drawbacks associated with their
      conventional dosage form. RESULTS: This manuscript presents an outline of the
      transdermal research specifically in the area of ARBs, ACEIs and other anti
      hypertensives reported in various pharmaceutical journals. CONCLUSION: The
      transdermal delivery has gained a significant importance for systemic treatment
      as it is able to avoid first-pass metabolism and major fluctuations of plasma
      levels typical of repeated oral administration. As we can experience from this
      review article that transdermal delivery of different ARBs and ACEIs improves
      bioavailability as well as patient compliance by many folds. In fact, the
      rationale development of some newer ARBs, ACEIs and other anti-hypertensives
      transdermal systems will provide new ways of treatment, circumventing current
      limitations for conventional dosage forms.

PMID- 25065884
TI  - Assays for necroptosis and activity of RIP kinases.
AB  - Necrosis is a primary form of cell death in a variety of human pathologies. The
      deleterious nature of necrosis, including its propensity to promote inflammation,
      and the relative lack of the cells displaying necrotic morphology under
      physiologic settings, such as during development, have contributed to the notion
      that necrosis represents a form of pathologic stress-induced nonspecific cell
      lysis. However, this notion has been challenged in recent years by the discovery
      of a highly regulated form of necrosis, termed regulated necrosis or necroptosis.
      Necroptosis is now recognized by the work of multiple labs, as an important, drug
      targetable contributor to necrotic injury in many pathologies, including ischemia
      reperfusion injuries (heart, brain, kidney, liver), brain trauma, eye diseases,
      and acute inflammatory conditions. In this review, we describe the methods to
      analyze cellular necroptosis and activity of its key mediator, RIP1 kinase. 

PMID- 25065885
TI  - IAP family of cell death and signaling regulators.
AB  - Inhibitor of apoptosis (IAP) proteins interface with, and regulate a large number
      of, cell signaling pathways. If there is a common theme to these pathways, it is
      that they are involved in the development of the immune system, immune responses,
      and unsurprisingly, given their name, cell death. Beyond that it is difficult to
      discover an underlying logic because sometimes IAPs are required to inhibit or
      prevent signaling, whereas in other cases they are required for signaling to take
      place. In whatever role they play, they are recruited into signaling complexes
      and function as ubiquitin E3 ligases, via their RING domains. This review
      discusses IAP regulation of signaling pathways and focuses on the mammalian IAPs,
      XIAP, c-IAP1, and c-IAP2, with a particular emphasis on techniques and methods
      that were used to uncover their roles. We also provide a perspective on targeting
      IAP proteins for therapeutic intervention and methods used to define the clinical
      relevance of IAP proteins. 

PMID- 25065886
TI  - Activation of the NLRP3 inflammasome by proteins that signal for necroptosis.
AB  - Necroptosis-a form of programmed necrotic cell death-and its resulting release of
      damage-associated molecular patterns (DAMPs) are believed to participate in the
      triggering of inflammatory processes. To assess the relative contribution of this
      cell death mode to inflammation, we need to know what other cellular effects can
      be exerted by molecules shown to trigger necrotic death, and the extent to which
      those effects might themselves contribute to inflammation. Here, we describe the
      technical approaches that have been applied to assess the impact of the main
      signaling molecules known to mediate activation of necroptosis upon generation of
      inflammatory cytokines in LPS-treated mouse bone marrow-derived dendritic cells.
      The findings obtained by this assessment indicated that signaling molecules known
      to initiate necroptosis can also initiate activation of the NLRP3 inflammasome,
      thereby inducing inflammation independently of cell death by triggering the
      generation of proinflammatory cytokines such as IL-1beta. 

PMID- 25065887
TI  - Characterization of the ripoptosome and its components: implications for anti
      inflammatory and cancer therapy.
AB  - Most intracellular signaling cascades rely on the formation of multiprotein
      signaling complexes assembled in large protein signaling platforms. Especially in
      cell death signaling, there is a large variety of these complexes, including the
      apoptosome, the necrosome, or the death-inducing signaling complex (DISC), to
      name only a few. During the last years, a number of cellular conditions were
      identified that lead to the formation of another signaling platform, the so
      called ripoptosome. Diverse stimuli such as genotoxic stress, death receptor or
      Toll-like-receptor (TLR) ligation, or degradation of cellular inhibitor of
      apoptosis proteins (cIAPs) are able to induce ripoptosome formation. The
      ripoptosome is tightly regulated by cIAPs that control intracellular RIP1
      assembly and the association with other cell death-regulating proteins, most
      likely by ubiquitin linkage. The suppression of cIAP activity results in
      accumulation of RIP1 platforms that ultimately triggers necroptosis by activation
      of RIP3-MLKL-dependent necrosis signaling pathways. The ripoptosome is a 2-MDa
      protein complex, which consists of the core components caspase-8, FADD, different
      cFLIP isoforms, and RIP1. It represents one of the rheostats in cell death
      signaling, as it can activate apoptotic and necroptotic cell death responses. The
      specific formation and activation of the ripoptosome in cancer but not in primary
      cells suggests that this complex is a potential novel target for cancer or anti
      inflammatory therapy, as suggested by the potential proinflammatory effects of
      necroptosis. Therefore, the better understanding and characterization of this
      signaling platform is of enormous importance for the development of novel cancer
      therapeutics. In this chapter, we describe several methods for purification and
      investigation of the ripoptosome in human cells. We also describe methods for
      monitoring apoptotic as well as necroptotic cell death.

PMID- 25065888
TI  - Tools and techniques to study ligand-receptor interactions and receptor
      activation by TNF superfamily members.
AB  - Ligands and receptors of the TNF superfamily are therapeutically relevant targets
      in a wide range of human diseases. This chapter describes assays based on ELISA,
      immunoprecipitation, FACS, and reporter cell lines to monitor interactions of
      tagged receptors and ligands in both soluble and membrane-bound forms using
      unified detection techniques. A reporter cell assay that is sensitive to ligand
      oligomerization can identify ligands with high probability of being active on
      endogenous receptors. Several assays are also suitable to measure the activity of
      agonist or antagonist antibodies, or to detect interactions with proteoglycans.
      Finally, self-interaction of membrane-bound receptors can be evidenced using a
      FRET-based assay. This panel of methods provides a large degree of flexibility to
      address questions related to the specificity, activation, or inhibition of TNF
      TNF receptor interactions in independent assay systems, but does not substitute
      for further tests in physiologically relevant conditions. 

PMID- 25065889
TI  - Necrotic cell death in Caenorhabditis elegans.
AB  - Similar to other organisms, necrotic cell death in the nematode Caenorhabditis
      elegans is manifested as the catastrophic collapse of cellular homeostasis, in
      response to overwhelming stress that is inflicted either in the form of extreme
      environmental stimuli or by intrinsic insults such as the expression of proteins
      carrying deleterious mutations. Remarkably, necrotic cell death in C. elegans and
      pathological cell death in humans share multiple fundamental features and
      mechanistic aspects. Therefore, mechanisms mediating necrosis are also conserved
      across the evolutionary spectrum and render the worm a versatile tool, with the
      capacity to facilitate studies of human pathologies. Here, we overview necrotic
      paradigms that have been characterized in the nematode and outline the cellular
      and molecular mechanisms that mediate this mode of cell demise. In addition, we
      discuss experimental approaches that utilize C. elegans to elucidate the
      molecular underpinnings of devastating human disorders that entail necrosis. 

PMID- 25065891
TI  - Autophagy and cell death in the fly.
AB  - Macroautophagy (hereafter referred to as autophagy) is a lysosome-dependent
      catabolic process that results in the degradation and recycling of cellular
      components, such as lipids, proteins, and organelles. Autophagy can function in
      many cellular contexts, including during infection, stress, cell survival, and
      cell death. During the development of the fruit fly Drosophila melanogaster,
      multiple tissues undergo a programmed cell death in which autophagy plays a key
      role in their destruction. Here, we describe how to analyze autophagy and its
      relationship to cell death in Drosophila. 

PMID- 25065890
TI  - Noncanonical cell death in the nematode Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans has served as a fruitful setting for cell
      death research for over three decades. A conserved pathway of four genes, egl
      1/BH3-only, ced-9/Bcl-2, ced-4/Apaf-1, and ced-3/caspase, coordinates most
      developmental cell deaths in C. elegans. However, other cell death forms,
      programmed and pathological, have also been described in this animal. Some of
      these share morphological and/or molecular similarities with the canonical
      apoptotic pathway, while others do not. Indeed, recent studies suggest the
      existence of an entirely novel mode of programmed developmental cell destruction
      that may also be conserved beyond nematodes. Here, we review evidence for these
      noncanonical pathways. We propose that different cell death modalities can
      function as backup mechanisms for apoptosis, or as tailor-made programs that
      allow specific dying cells to be efficiently cleared from the animal. 

PMID- 25065892
TI  - Structural studies of death receptors.
AB  - This chapter describes reports of the structural characterization of death
      ligands and death receptors (DRs) from the tumor necrosis factor (TNF) and TNF
      receptor families. The review discusses the interactions of these proteins with
      agonist ligands, inhibitors, and downstream signaling molecules. Though
      historically labeled as being implicated in programmed cell death, the function
      of these proteins extends to nonapoptotic pathways. The review highlights, from a
      structural biology perspective, the complexity of DR signaling and the ongoing
      challenge to discern the precise mechanisms that occur at the point of DR
      activation, including how the degree to which the receptors are induced to
      cluster may be related to the nature of the impact upon the cell. The potential
      for posttranslational modification and receptor internalization to play roles in
      DR signaling is briefly discussed. 

PMID- 25065893
TI  - Use of E2~ubiquitin conjugates for the characterization of ubiquitin transfer by
      RING E3 ligases such as the inhibitor of apoptosis proteins.
AB  - Ubiquitylation of proteins is a versatile posttranslational modification that can
      serve to promote protein degradation, or it can have nondegradative roles, such
      as mediating protein-protein interactions. The Inhibitor of APoptosis (IAP)
      proteins are important regulators of pathways that control cell death,
      proliferation, and differentiation. A number of IAP family members are RING E3
      ubiquitin-protein ligases, which promote direct transfer of ubiquitin from
      charged E2 enzymes, or E2~ubiquitin (E2~Ub) conjugates, to substrate proteins.
      This results in the attachment of nondegradative ubiquitin signals to other
      proteins, or the autoubiquitylation and degradation of IAPs. Modulating ubiquitin
      transfer by IAPs is the focus of a number of drug development initiatives and
      these studies require a detailed understanding of ubiquitylation. Here, we
      describe preparation of stable E2~Ub conjugates that can be used in biochemical
      and biophysical experiments to examine RING domain function. In the last 2 years,
      the availability of these conjugates has helped unveil a molecular understanding
      of the process of ubiquitin transfer by IAPs. The approaches described here will
      be suitable for studying other RING E3 ligases. 

PMID- 25065894
TI  - Multidimensional profiling in the investigation of small-molecule-induced cell
      death.
AB  - Numerous morphological variations of cell death have been described. These
      processes depend on a complex and overlapping cellular signaling network, making
      molecular definition of the pathways challenging. This review describes one
      solution to this problem for small-molecule-induced death, the creation of high
      dimensionality profiles for compounds that can be used to define and compare
      pathways. Such profiles have been assembled from gene expression measurements,
      protein quantification, chemical-genetic interactions, chemical combination
      interactions, cancer cell line sensitivity profiling, quantitative imaging, and
      modulatory profiling. We discuss the advantages and limitations of these
      techniques in the study of cell death. 

PMID- 25065895
TI  - Methods in Enzymology. Regulated cell death part B--necroptotic, autophagic and
      other non-apoptotic mechanisms. Preface.

PMID- 25065896
TI  - Molecular imaging in the management of gynecologic malignancies.
AB  - OBJECTIVES: The purpose of this review is to summarize literature pertaining to
      clinical roles of positron emission tomography (PET) or integrated PET and
      computed tomography (PET/CT) scans, magnetic resonance imaging (MRI) and emerging
      techniques of these two molecular imaging tools for gynecologic malignancies.
      METHODS: PubMed and MEDLINE databases search for articles published before June
      2014 was performed. Only English-language articles were considered. Search terms
      included "cervical cancer", "endometrial cancer", "uterine cancer", "uterine
      sarcoma", "ovarian cancer" and "vulvar cancer", in association with "FDG", "PET",
      "PET/CT", "MRI", "PET/MR", "diffusion", "spectroscopy" and "clinical trial".
      RESULTS: Topics explored included PET, PET/CT and MRI for diagnosis of
      malignancy, prognostic implications, clinical staging of disease extent,
      monitoring treatment response, post-therapy surveillance, diagnosis of treatment
      failure and restaging, and follow-up after salvage therapy in gynecologic
      malignancies. CONCLUSIONS: Molecular imaging (mainly PET and MRI) plays important
      roles in the management of gynecologic malignancies. Molecular imaging has
      various impacts in different clinical scenarios. Emerging technologies will
      continuously improve our practice. Prospective studies with defined endpoints are
      necessary to evaluate roles of these novel tools in management of gynecologic
      malignancies.

PMID- 25065897
TI  - Rebound thymic hyperplasia detected by 18F-FDG PET/CT after radioactive iodine
      ablation therapy for thyroid cancer.
AB  - BACKGROUND: Rebound thymic hyperplasia (RTHP) is not an uncommon finding after
      radiation or chemotherapy in patients with various malignancies. However, there
      are limited case reports of this phenomenon after radioactive iodine ablation
      therapy (RIAT) in differentiated thyroid cancer (DTC). The goal of this study was
      to evaluate the incidence, patterns, and factors affecting RTHP after RIAT using
      (18)F-FDG PET/CT. METHODS: The study design was a retrospective review of 2550
      patients (568 men, 1982 women; age 13-79 years) who underwent FDG PET/CT imaging
      after total thyroidectomy and RIAT from June 2009 through June 2012. Patients
      were divided into four age-related subgroups. Overall incidence, age-related
      incidences, and sex distribution were evaluated in patients with thymic FDG
      uptake on PET/CT (RTHP+). The correlation between incidence of RTHP and age was
      assessed using the Cochran-Armitage trend test. The Wilcoxon rank-sum test and
      multiple regression were applied to investigate the effect of applied dose of
      radioactive iodine (RAI) and age on the incidence of RTHP. Correlations of
      standardized uptake value (SUV) and thymic volume with age and morphologic type
      were also evaluated. RESULTS: Overall incidence of RTHP after RIAT was 1.49%, and
      all of the RTHP+ patients except one were female. The Cochran-Armitage trend test
      revealed significantly decreased incidence from the second to fifth decade
      (8.84%, 1.74%, 0.98%, and 0.39% respectively; p<0.001). In each age-related
      subgroup, the RAI dose was significantly higher in the RTHP+ than RTHP- group
      (p<0.001), while there was no difference in RAI dose in RTHP+ patients among age
      related subgroups (p=0.838). SUVmean and SUVmax of RTHP revealed no meaningful
      correlation with RAI dose or age. There were no differences among morphologic
      patterns of RTHP in age distribution and ablation dose. CONCLUSIONS: RTHP after
      RIAT showed a strong female predominance, despite the higher administration dose
      of RAI in male patients. Although the decreased incidence of RTHP after RIAT with
      age is similar to the pattern of RTHP induced by other causes, the fact that
      older patients, even sixth decade patients, can present with RTHP after RIAT is
      noteworthy in the management of DTC.

PMID- 25065898
TI  - Flame spray pyrolysis for finding multicomponent nanomaterials with superior
      electrochemical properties in the CoO(x)-FeO(x) system for use in lithium-ion
      batteries.
AB  - High-temperature flame spray pyrolysis is employed for finding highly efficient
      nanomaterials for use in lithium-ion batteries. CoO(x)-FeO(x) nanopowders with
      various compositions are prepared by one-pot high-temperature flame spray
      pyrolysis. The Co and Fe components are uniformly distributed over the CoO(x)
      FeO(x) composite powders, irrespective of the Co/Fe mole ratio. The Co-rich
      CoO(x)-FeO(x) composite powders with Co/Fe mole ratios of 3:1 and 2:1 have mixed
      crystal structures with CoFe2O4 and Co3O4 phases. However, Co-substituted
      magnetite composite powders prepared from spray solutions with Co and Fe
      components in mole ratios of 1:3, 1:2, and 1:1 have a single phase.
      Multicomponent CoO(x)-FeO(x) powders with a Co/Fe mole ratio of 2:1 and a mixed
      crystal structure with Co3O4 and CoFe2O4 phases show high initial capacities and
      good cycling performance. The stable reversible discharge capacities of the
      composite powders with a Co/Fe mole ratio of 2:1 decrease from 1165 to 820 mA h
      g(-1) as the current density is increased from 500 to 5000 mA g(-1); however, the
      discharge capacity again increases to 1310 mA h g(-1) as the current density is
      restored to 500 mA g(-1).

PMID- 25065899
TI  - Genomics of the divergence continuum in an African plant biodiversity hotspot, I:
      drivers of population divergence in Restio capensis (Restionaceae).
AB  - Understanding the drivers of population divergence, speciation and species
      persistence is of great interest to molecular ecology, especially for species
      rich radiations inhabiting the world's biodiversity hotspots. The toolbox of
      population genomics holds great promise for addressing these key issues,
      especially if genomic data are analysed within a spatially and ecologically
      explicit context. We have studied the earliest stages of the divergence continuum
      in the Restionaceae, a species-rich and ecologically important plant family of
      the Cape Floristic Region (CFR) of South Africa, using the widespread CFR endemic
      Restio capensis (L.) H.P. Linder & C.R. Hardy as an example. We studied diverging
      populations of this morphotaxon for plastid DNA sequences and >14 400 nuclear DNA
      polymorphisms from Restriction site Associated DNA (RAD) sequencing and analysed
      the results jointly with spatial, climatic and phytogeographic data, using a
      Bayesian generalized linear mixed modelling (GLMM) approach. The results indicate
      that population divergence across the extreme environmental mosaic of the CFR is
      mostly driven by isolation by environment (IBE) rather than isolation by distance
      (IBD) for both neutral and non-neutral markers, consistent with genome
      hitchhiking or coupling effects during early stages of divergence. Mixed
      modelling of plastid DNA and single divergent outlier loci from a Bayesian genome
      scan confirmed the predominant role of climate and pointed to additional drivers
      of divergence, such as drift and ecological agents of selection captured by
      phytogeographic zones. Our study demonstrates the usefulness of population
      genomics for disentangling the effects of IBD and IBE along the divergence
      continuum often found in species radiations across heterogeneous ecological
      landscapes.

PMID- 25065900
TI  - Peptide modifications differentially alter G protein-coupled receptor
      internalization and signaling bias.
AB  - Although G protein-coupled receptors (GPCRs) are targeted by more clinically used
      drugs than any other type of protein, their ligand development is particularly
      challenging. Humans have four neuropeptide Y receptors: hY1R and hY5R are
      orexigenic, while hY2R and hY4R are anorexigenic, and represent important anti
      obesity drug targets. We show for the first time that PEGylation and lipidation,
      chemical modifications that prolong the plasma half-lives of peptides, confer
      additional benefits. Both modifications enhance pancreatic polypeptide preference
      for hY2R/hY4R over hY1R/hY5R. Lipidation biases the ligand towards arrestin
      recruitment and internalization, whereas PEGylation confers the opposite bias.
      These effects were independent of the cell system and modified residue. We thus
      provide novel insights into the mode of action of peptide modifications and open
      innovative venues for generating peptide agonists with extended therapeutic
      potential.

PMID- 25065901
TI  - Benefits to poorly studied taxa of conservation of bird and mammal diversity on
      islands.
AB  - Protected area delineation and conservation action are urgently needed on marine
      islands, but the potential biodiversity benefits of these activities can be
      difficult to assess due to lack of species diversity information for lesser known
      taxa. We used linear mixed effects modeling and simple spatial analyses to
      investigate whether conservation activities based on the diversity of well-known
      insular taxa (birds and mammals) are likely to also capture the diversity of
      lesser known taxa (reptiles, amphibians, vascular land plants, ants, land snails,
      butterflies, and tenebrionid beetles). We assembled total, threatened, and
      endemic diversity data for both well-known and lesser known taxa and combined
      these with physical island biogeography characteristics for 1190 islands from 109
      archipelagos. Among physical island biogeography factors, island area was the
      best indicator of diversity of both well-known and little-known taxa. Among
      taxonomic factors, total mammal species richness was the best indicator of total
      diversity of lesser known taxa, and the combination of threatened mammal and
      threatened bird diversity was the best indicator of lesser known endemic
      richness. The results of other intertaxon diversity comparisons were highly
      variable, however. Based on our results, we suggest that protecting islands above
      a certain minimum threshold area may be the most efficient use of conservation
      resources. For example, using our island database, if the threshold were set at
      10 km(2) and the smallest 10% of islands greater than this threshold were
      protected, 119 islands would be protected. The islands would range in size from
      10 to 29 km(2) and would include 268 lesser known species endemic to a single
      island, along with 11 bird and mammal species endemic to a single island. Our
      results suggest that for islands of equivalent size, prioritization based on
      total or threatened bird and mammal diversity may also capture opportunities to
      protect lesser known species endemic to islands.

PMID- 25065902
TI  - Neurodevelopmental origin of cognitive impairment in schizophrenia.
AB  - Cognitive impairment is a common feature of schizophrenia; however, its origin
      remains controversial. Neurodevelopmental abnormalities clearly play a role in
      pre-morbid cognitive dysfunction in schizophrenia, yet many authors believe that
      schizophrenia is characterized by illness-related cognitive decline before and
      after onset of the psychosis that can be the result of neurodegenerative changes.
      The main reasons behinds such arguments include, first, the evidence showing that
      effect sizes of the cognitive deficits in subjects who develop adult
      schizophrenia gradually increase in the first two decades of life and, second,
      the fact that there is functional decline in many patients with schizophrenia
      over the years. In this Editorial, I argue that current evidence suggests that
      illness-related cognitive impairment is neurodevelopmental in origin and
      characterized by slower gain (developmental lag) but not cognitive decline
      continuing throughout the first two decades of life. I introduce a model
      suggesting that neurodevelopmental abnormality can in fact explain the course of
      cognitive dysfunction and variations in the trajectory of functional decline
      throughout the life in individuals with schizophrenia. In this model, the
      severity of underlying neurodevelopmental abnormality determines the age that
      cognitive deficits first become apparent and contributes to the cognitive reserve
      of the individual. Interaction of neurodevelopmental abnormality with clinical
      symptoms, especially negative symptoms and aging, vascular changes, psychological
      and iatrogenic factors contributes to the heterogeneity of the functional
      trajectory observed in this disorder. 

PMID- 25065903
TI  - Clear cell carcinoma of the ovary: evaluation of prognostic parameters based on a
      clinicopathological analysis of 100 cases.
AB  - AIMS: The aim of this study was to evaluate the clinicopathological features of
      ovarian clear cell carcinomas in order to identify which, if any, are
      prognostically significant, and to determine whether there is value in grading
      these tumours. METHODS AND RESULTS: One hundred tumours with clinical follow-up
      were reviewed. Features evaluated included age, preoperative/intraoperative
      rupture, size, architectural pattern(s), presence of oxyphilic cells, degree of
      cytological atypia, nucleolar grade, mitoses, background precursor and stage.
      Survival differences were analysed using the log-rank test and Kaplan-Meier
      estimator. Stage and lymph node status were the only parameters that were
      statistically significant (P < 0.0001). Patients with stage I disease (71%) had a
      92% 5-year survival compared to a 31% 5-year survival in advanced stage disease
      (29%). Those with negative lymph nodes (92%) had an 80% 5-year survival compared
      to a 22% 5-year survival for those with positive nodes (8%). CONCLUSIONS: This
      study shows that stage and lymph node status are the only prognostically
      significant parameters in patients with ovarian clear cell carcinoma. It also
      confirms that most patients with clear cell carcinoma present with disease
      confined to the ovary, and have an excellent prognosis. Grading ovarian clear
      cell carcinomas based on morphological features is not recommended, as none are
      of prognostic significance.

PMID- 25065904
TI  - Noninvasive measurement of liver fibrosis using transient elastography in
      pediatric patients with major thalassemia who are candidates for hematopoietic
      stem cell transplantation.
AB  - Although liver biopsy is an invasive procedure, it remains the gold standard
      technique for the evaluation of hepatic fibrosis in different patients, including
      those with major thalassemia (MT). Recently, noninvasive imaging techniques, such
      as transient elastography, have emerged. We investigated the effectiveness of TE,
      in comparison to liver biopsy, for the evaluation of liver fibrosis in pediatric
      patients with MT who were candidates for hematopoietic stem cell transplantation
      (HSCT). Eighty-three pediatric MT patients (48 boys and 35 girls), who were
      candidates for HSCT, were included in this study. The median age was 8 years.
      Liver stiffness was assessed for all patients, before transplantation, using both
      TE, measured in kilopascals (kPa) and liver biopsy, based on the Metavir score.
      The diagnostic accuracy of TE and liver biopsy were estimated using linear
      discriminated analysis (the area under the receiver operating characteristic
      curves [AUROCs]). The median TE score was 4.3 kPa (range, 3.5 to 5.2). The TE
      value did not differ among patients with different ferritin levels (P = .53). TE
      increased proportionally to Metavir fibrosis stages (P < .001) and the necro
      inflammatory grade (P < .001). The TE score also correlated to liver iron content
      (P < .001), liver size (P < .003), and Lucarelli risk classification (LRC) (P <
      .001). ROC curve analysis revealed moderate accuracy of the TE score for the
      diagnosis of fibrosis (AUROC = 73%) and for distinguishing individuals with a LRC
      III from those classified as I and II (AUROC = 82%). The TE score was also
      superior to Fibrosis-4 (AUROC = 61%) for the assessment of liver fibrosis and LRC
      differentiation. The results of this study demonstrated that TE can be a valuable
      method for assessing liver fibrosis and differentiating LRC III from the other 2
      classes in pediatric patients with MT who have been selected for HSCT. 

PMID- 25065905
TI  - Maximizing the benefits of mycophenolate mofetil as graft-versus-host disease
      prophylaxis.

PMID- 25065906
TI  - Cholangiocyte lipoapoptosis: implications for biliary damage during nonalcoholic
      fatty liver disease.

PMID- 25065907
TI  - Echocardiography detection of fetal ventricular aneurysm: A report of three
      cases.
AB  - From March 2007 to September 2009, we have screened with echocardiography a total
      of 6,502 pregnant women for fetal heart disease. We found three cases of fetal
      ventricular aneurysm. The relatively large size of the aneurysm in these three
      cases was clearly visible under standard four-chamber view. Two were right
      ventricular aneurysms arisen from the ventricular free wall, and both showed
      characteristics of true aneurysm with a thin wall and a large communication with
      the ventricular chamber. Color Doppler showed passive movement of aneurysm during
      right ventricle contraction. The third case was a large left ventricular aneurysm
      outpouching from a small opening of the left ventricular wall close to the apical
      region. (c) 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:257-261, 2015.

PMID- 25065908
TI  - A fresh look at the use of nonparametric analysis in actimetry.
AB  - Actimetry has been used to estimate the sleep-wake cycle instead of the rest
      activity rhythm. Although algorithms for assessing sleep from actimetry data
      exist, it is useful to analyze the rest-activity rhythm using nonparametric
      methods. This would then allow rest-activity rhythm stability, fragmentation and
      amplitude to be quantified. In addition, sleep and wakefulness efficiency can be
      quantified separately. These variables have been used in studies analyzing the
      effect of age, diseases and their respective treatments on human circadian
      rhythmicity. In this study, we carried out a comprehensive analysis of the main
      results from published articles and devised a functional model of interaction
      among the several components involved in generating the sleep-wake cycle. The
      nonparametric variables render it possible to infer the main characteristics of
      circadian rhythms, such as synchronization with a zeitgeber, and its amplitude
      and robustness. 

PMID- 25065909
TI  - Foreword.

PMID- 25065910
TI  - Expected population impacts of discontinued prostate-specific antigen screening.
AB  - BACKGROUND: Prostate-specific antigen (PSA) screening for prostate cancer has
      high risks of overdiagnosis, particularly among older men, and reports from
      screening trials indicate that it saves few lives after 11 to 13 years of follow
      up. New clinical guidelines recommend against PSA screening for all men or for
      men aged >70 years, but, to the authors' knowledge, the expected population
      effects of these guidelines have not been studied to date. METHODS: Two models of
      prostate cancer natural history and diagnosis were previously developed using
      reconstructed PSA screening patterns and prostate cancer incidence in the United
      States. Assuming a survival benefit of PSA screening consistent with the
      screening trials, the authors used the models to predict incidence and mortality
      rates for the period from 2013 through 2025 under continued PSA screening and
      under discontinued PSA screening for all men or for men aged >70 years. RESULTS:
      The models predicted that continuation of recent screening rates will
      overdiagnose 710,000 to 1,120,000 men (range between models) but will avoid
      36,000 to 57,000 cancer deaths over the period 2013 through 2025. Discontinued
      screening for all men eliminated 100% of overdiagnoses but failed to prevent 100%
      of avoidable cancer deaths. Continued screening for men aged <70 years eliminated
      64% to 66% of overdiagnoses but failed to prevent 36% to 39% of avoidable cancer
      deaths. CONCLUSIONS: Discontinuing PSA screening for all men may generate many
      avoidable cancer deaths. Continuing PSA screening for men aged <70 years could
      prevent greater than one-half of these avoidable cancer deaths while dramatically
      reducing overdiagnoses compared with continued PSA screening for all ages.

PMID- 25065912
TI  - Diagnostic sensitivity of ultrasound, radiography and computed tomography for
      gender determination in four species of lizards.
AB  - Gender determination is frequently requested by reptile breeders, especially for
      species with poor or absent sexual dimorphism. The aims of the current study were
      to describe techniques and diagnostic sensitivities of ultrasound, radiography,
      and computed tomography for gender determination (identification of hemipenes) in
      four species of lizards. Nineteen lizards of known sex, belonging to four
      different species (Pogona vitticeps, Uromastyx aegyptia, Tiliqua scincoides,
      Gerrhosaurus major) were prospectively enrolled. With informed owner consent,
      ultrasound, noncontrast CT, contrast radiography, and contrast CT (with contrast
      medium administered into the cloaca) were performed in conscious animals. Imaging
      studies were reviewed by three different operators, each unaware of the gender of
      the animals and of the results of the other techniques. The lizard was classified
      as a male when hemipenes were identified. Nineteen lizards were included in the
      study, 10 females and nine males. The hemipenes were seen on ultrasound in only
      two male lizards, and appeared as oval hypoechoic structures. Radiographically,
      hemipenes filled with contrast medium appeared as spindle-shaped opacities.
      Noncontrast CT identified hemipenes in only two lizards, and these appeared as
      spindle-shaped kinked structures with hyperattenuating content consistent with
      smegma. Hemipenes were correctly identified in all nine males using contrast CT
      (accuracy of 100%). Accuracy of contrast radiography was excellent (94.7%).
      Accuracy of ultrasound and of noncontrast CT was poor (64.3% and 63.1%,
      respectively). Findings from the current study supported the use of contrast CT
      or contrast radiography for gender determination in lizards. 

PMID- 25065911
TI  - Subtypes of major depression: latent class analysis in depressed Han Chinese
      women.
AB  - BACKGROUND: Despite substantial research, uncertainty remains about the clinical
      and etiological heterogeneity of major depression (MD). Can meaningful and valid
      subtypes be identified and would they be stable cross-culturally? METHOD:
      Symptoms at their lifetime worst depressive episode were assessed at structured
      psychiatric interview in 6008 women of Han Chinese descent, age ? 30 years, with
      recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus. RESULTS;
      Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV
      criteria and all independently assessed depressive symptoms (n = 27), the best
      LCA model identified respectively three, four and six classes. A severe and non
      suicidal class was seen in all solutions, as was a mild/moderate subtype. An
      atypical class emerged once bidirectional neurovegetative symptoms were included.
      The non-suicidal class demonstrated low levels of worthlessness/guilt and
      hopelessness. Patterns of co-morbidity, family history, personality,
      environmental precipitants, recurrence and body mass index (BMI) differed
      meaningfully across subtypes, with the atypical class standing out as
      particularly distinct. CONCLUSIONS: MD is a clinically complex syndrome with
      several detectable subtypes with distinct clinical and demographic correlates.
      Three subtypes were most consistently identified in our analyses: severe,
      atypical and non-suicidal. Severe and atypical MD have been identified in
      multiple prior studies in samples of European ethnicity. Our non-suicidal
      subtype, with low levels of guilt and hopelessness, may represent a pathoplastic
      variant reflecting Chinese cultural influences.

PMID- 25065913
TI  - ELOVL5 mutations cause spinocerebellar ataxia 38.
AB  - Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant
      neurodegenerative disorders involving the cerebellum and 23 different genes. We
      mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family
      by whole-genome linkage analysis. Targeted resequencing identified a single
      missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456
      independent SCA-affected individuals identified the same mutation in two further
      unrelated Italian families. Haplotyping showed that at least two of the three
      families shared a common ancestor. One further missense variant (c.214C>G
      [p.Leu72Val]) was found in a French family. Both missense changes affect
      conserved amino acids, are predicted to be damaging by multiple bioinformatics
      tools, and were not identified in ethnically matched controls or within variant
      databases. ELOVL5 encodes an elongase involved in the synthesis of
      polyunsaturated fatty acids of the omega3 and omega6 series. Arachidonic acid and
      docosahexaenoic acid, two final products of the enzyme, were reduced in the serum
      of affected individuals. Immunohistochemistry on control mice and human brain
      demonstrated high levels in Purkinje cells. In transfection experiments,
      subcellular localization of altered ELOVL5 showed a perinuclear distribution with
      a signal increase in the Golgi compartment, whereas the wild-type showed a
      widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of
      SCAs due to mutations in elongase-encoding genes, emphasizing the importance of
      fatty-acid metabolism in neurological diseases. 

PMID- 25065915
TI  - Blistering time as a parameter for the strength of dermoepidermal adhesion: a
      systematic review and meta-analysis.
AB  - Skin ageing is associated with a flattening of the dermoepidermal junction and a
      less effective anchoring system, predisposing to bulla formation, trauma and
      shear-type injuries. An artificial and controlled technique for standardized
      dermoepidermal separation is the suction blister method, whereby the strength of
      dermoepidermal adhesion is characterized by blistering time. To identify and
      quantify influencing factors on blistering time in healthy humans. A search in
      the Medline and Embase databases (1946 to June 2014) and in reference lists was
      conducted. In total, results of 146 suction blister experiments in 3418
      individuals reported in 59 publications were analysed. The median blister
      diameter was 6 mm (IQR 5-6) and the median suction pressure was -210 mmHg (IQR 
      200 to -300), resulting in a median blistering time of 75 min (IQR 48-120). In
      the multivariate model, skin temperature and age were the strongest predictors
      for suction blistering time (P < 0.001, R(2) adjusted  = 0.707). This strong
      association between temperature and suction blistering indicates that the
      dermoepidermal junction loses its strength with increasing skin temperature. This
      finding supports the practice of skin and tissue cooling to prevent injuries. The
      increased vulnerability of the skin seems to exist irrespectively of applied
      mechanical loads. We conclude that blistering time is an important and clinically
      relevant (outcome) parameter measuring the structural and mechanical integrity of
      deeper cutaneous layers. 

PMID- 25065916
TI  - Obesity, metabolic abnormality, and knee osteoarthritis: a cross-sectional study
      in Korean women.
AB  - BACKGROUND: This study aimed to analyze the association between knee
      osteoarthritis and four body size phenotypes defined by the presence or absence
      of metabolic abnormality and obesity. MEHODS: This was a cross-sectional study
      using data from 1,549 female participants of the Fifth Korean National Health and
      Nutrition Examination Survey. Knee osteoarthritis was defined as a Kellgren
      Lawrence grade of >= 2. Metabolically abnormal state was defined as presence of
      more than one abnormality among five metabolic risk factors. Obesity was defined
      using body mass index. Participants were grouped into one of the four body size
      phenotypes: metabolically healthy normal weight (MHNW), metabolically abnormal
      but normal weight (MANW), metabolically healthy obesity (MHO), and metabolically
      abnormal obesity (MAO). RESULTS: The distribution of each body size phenotype was
      as follows: MHNW 54.7%, MANW 30.7%, MHO 4.3%, and MAO 10.3%. Prevalence of
      symptomatic knee osteoarthritis was higher in MANW than in MHNW, and in MAO than
      in MHO. In multivariable analysis, the association between symptomatic knee
      osteoarthritis and the body size phenotypes was as follows (OR [95% CI]): MHNW
      1.00 (reference), MANW 1.54 (1.15-2.07), MHO 1.61 (0.83-3.13), and MAO 3.47 (2.35
      5.14). CONCLUSIONS: Obesity showed closest association with knee osteoarthritis
      when accompanied by metabolic abnormality.

PMID- 25065914
TI  - The Alu-rich genomic architecture of SPAST predisposes to diverse and
      functionally distinct disease-associated CNV alleles.
AB  - Intragenic copy-number variants (CNVs) contribute to the allelic spectrum of both
      Mendelian and complex disorders. Although pathogenic deletions and duplications
      in SPAST (mutations in which cause autosomal-dominant spastic paraplegia 4
      [SPG4]) have been described, their origins and molecular consequences remain
      obscure. We mapped breakpoint junctions of 54 SPAST CNVs at nucleotide
      resolution. Diverse combinations of exons are deleted or duplicated, highlighting
      the importance of particular exons for spastin function. Of the 54 CNVs, 38 (70%)
      appear to be mediated by an Alu-based mechanism, suggesting that the Alu-rich
      genomic architecture of SPAST renders this locus susceptible to various genome
      rearrangements. Analysis of breakpoint Alus further informs a model of Alu
      mediated CNV formation characterized by small CNV size and potential involvement
      of mechanisms other than homologous recombination. Twelve deletions (22%) overlap
      part of SPAST and a portion of a nearby, directly oriented gene, predicting novel
      chimeric genes in these subjects' genomes. cDNA from a subject with a SPAST final
      exon deletion contained multiple SPAST:SLC30A6 fusion transcripts, indicating
      that SPAST CNVs can have transcriptional effects beyond the gene itself. SLC30A6
      has been implicated in Alzheimer disease, so these fusion gene data could explain
      a report of spastic paraplegia and dementia cosegregating in a family with
      deletion of the final exon of SPAST. Our findings provide evidence that the Alu
      genomic architecture of SPAST predisposes to diverse CNV alleles with distinct
      transcriptional--and possibly phenotypic--consequences. Moreover, we provide
      further mechanistic insights into Alu-mediated copy-number change that are
      extendable to other loci.

PMID- 25065917
TI  - Efficacy of the clinical use of iguratimod therapy in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Iguratimod (IGU) is a new synthetic disease-modifying antirheumatic
      drug intended to treat patients with rheumatoid arthritis (RA). We conducted a 24
      week study on the efficacy of IGU in RA patients with daily clinical use.
      METHODS: Forty-one patients were enrolled in this study, and the improvement in
      RA was evaluated every 4 weeks during the 24 weeks. RESULTS: The patient's global
      assessment of the disease activity with a scale (Pt VAS) was significantly
      decreased beginning at week 4. The disease activity score (DAS) 28-erythrocyte
      sedimentation rate, DAS28-C-reactive protein (CRP), simplified disease activity
      index and clinical disease activity index all significantly decreased at week 24.
      The matrix metalloproteinase-3 level was significantly decreased by the
      combination treatment with methotrexate at week 24. According to a logistic
      regression analysis, the factor which was most associated with the achievement of
      low disease activity (DAS28-CRP < 2.7) at week 24 was the DAS28-CRP at week 0.
      CONCLUSIONS: IGU had significant clinical effects on the RA patients within 24
      weeks. IGU might therefore represent a new practical choice to treat RA patients.

PMID- 25065918
TI  - Construct validity, reliability, response rate, and association with disease
      activity of the quick disabilities of the arm, shoulder and hand questionnaire in
      the assessment of rheumatoid arthritis.
AB  - OBJECTIVE: First objective is to validate the Disabilities of the Arm, Shoulder
      and Hand (DASH) and Quick DASH (QuickDASH) questionnaire in rheumatoid arthritis
      (RA) patients with functional upper extremity impairment. Next is to clarify
      which clinical factor is associating with QuickDASH using a large cohort of RA.
      METHODS: The QuickDASH and DASH were applied to our 94 RA patients who underwent
      surgery for functional upper extremity impairment. Next, the QuickDASH was
      applied to our cohort of 5191 Japanese patients with RA. RESULTS: In the first
      cohort of 94 RA patients, both QuickDASH and DASH displayed excellent reliability
      and validity. The response rate of patients < 65 and >= 65 years of age showed
      significant difference in the DASH but not in the QuickDASH. In the second cohort
      with 5191 RA patients, QuickDASH showed a high response rate (93%) and good to
      moderate correlation with Japanese version of the Health Assessment Questionnaire
      (r = 0.88) and disease activity score of 28 (DAS28, r = 0.53). Change in
      QuickDASH score and DAS28-based European League Against Rheumatism response
      showed significant correlation. CONCLUSION: QuickDASH seems suitable for
      evaluating upper extremity impairment, disability index, and disease control in a
      large cohort of RA patients including elderly patients.

PMID- 25065919
TI  - Characteristics of granulomatosis with polyangiitis patients in Japan.
AB  - OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV) is a disease with significant ethnic differences. Reports on
      characteristics of Japanese granulomatosis with polyangiitis (GPA) patients are
      limited, and this study was undertaken to determine the characteristics of
      Japanese GPA patients. METHODS: This was a retrospective chart study of 24
      Japanese GPA patients. GPA was defined according to the European Medicines Agency
      algorithm. RESULTS: The percentage of MPO-ANCA-positive patients was 33.3%,
      higher than the percentages reported in studies from Western countries. MPO-ANCA
      positive GPA patients differed from PR3-ANCA-positive GPA patients in organs
      involved at diagnosis with MPO-ANCA-positive patients having nose and sinus
      involvement less frequently compared to PR3-ANCA-positive patients. Interstitial
      lung infiltrates were more common among MPO-ANCA-positive GPA patients compared
      to PR3-ANCA-positive GPA patients. CONCLUSION: Among Japanese GPA patients, the
      proportion of MPO-ANCA-positive patients is higher compared to reports from
      Western countries, and those patients are often different from the classical
      picture of GPA.

PMID- 25065920
TI  - Does Pattern Scan Laser (PASCAL) photocoagulation really induce less VEGF
      expression in murine retina than conventional laser treatment?
AB  - To investigate the differences in the mRNA and protein expression levels of
      vascular endothelial growth factor (VEGF) in murine retina between mice subjected
      to conventional laser (AG) and those subjected to Pattern Scan Laser (PASCAL)
      system. Male C57BL/6 mice were randomly assigned to one of three groups: Group 1
      (G1) receiving retinal scatter laser photocoagulation using with AG
      photocoagulator (n=16), Group 2 (G2) receiving retinal scatter laser
      photocoagulation using with PASCAL (n=16) and Group 3 (G3) served as an untreated
      control group (n=6). Molecular and morphological analyses of VEGF were performed
      on days 1, 2 and 5 by ELISA, real-time PCR and immuno-histochemical analysis. In
      samples which underwent AG (G1), when compared with the control group (G3), VEGF
      mRNA level increased 2.4 folds on day 2, whereas it decreased on day 5 (p?0.001).
      In samples which underwent PASCAL (G2), on the other hand, VEGF mRNA level
      increased 1.8 folds on day 1 and 2.2 folds on day 5 when compared with the
      control group (G3). In samples which underwent AG (G1), when compared with the
      control group (G3), VEGF protein level increased significantly on day 2, whereas
      it decreased on day 5 (p?0.001). In group G2, the VEGF levels in the sensory
      retina significantly increased as compared to control groups at both 2 and 5 days
      after laser photocoagulation using PASCAL laser (p=0.012, both time points). The
      peak expressions of VEGF protein in samples which underwent PASCAL and
      conventional laser were found on day 5 and day 2 respectively. In retinas of
      PASCAL-treated mice, VEGF immunoreactivity gradually increased during the 5-day
      follow-up. However, in argon laser group, the strongest VEGF immunoreactivity was
      detected on day 2, then started to decrease on day 5. In summary, the expression
      of VEGF protein and mRNA gradually increase during a 5-day follow-up period in
      PASCAL-treated mouse eyes, whereas in AG group they reach their peak levels on
      the second day of follow-up and started decreasing after then. These results may
      also explain why the PASCAL system is less effective in regressing
      neovascularization in the clinic.

PMID- 25065921
TI  - Cucumis sativus L-type lectin receptor kinase (CsLecRK) gene family response to
      Phytophthora melonis, Phytophthora capsici and water immersion in disease
      resistant and susceptible cucumber cultivars.
AB  - L-type lectin receptor kinase (LecRK) proteins are an important family involved
      in diverse biological processes such as pollen development, senescence, wounding,
      salinity and especially in innate immunity in model plants such as Arabidopsis
      and tobacco. Till date, LecRK proteins or genes of cucumber have not been
      reported. In this study, a total of 25 LecRK genes were identified in the
      cucumber genome, unequally distributed across its seven chromosomes. According to
      similarity comparison of their encoded proteins, the Cucumis sativus LecRK
      (CsLecRK) genes were classified into six major clades (from Clade I to CladeVI).
      Expression of CsLecRK genes were tested using QRT-PCR method and the results
      showed that 25 CsLecRK genes exhibited different responses to abiotic (water
      immersion) and biotic (Phytophthora melonis and Phytophthora capsici inoculation)
      stresses, as well as that between disease resistant cultivar (JSH) and disease
      susceptible cultivar (B80). Among the 25 CsLecRK genes, we found CsLecRK6.1 was
      especially induced by P. melonis and P. capsici in JSH plants. All these results
      suggested that CsLecRK genes may play important roles in biotic and abiotic
      stresses.

PMID- 25065922
TI  - Molecular evolution of growth hormone and insulin-like growth factor 1 receptors
      in long-lived, small-bodied mammals.
AB  - Mammals typically display a robust positive relationship between lifespan and
      body size. Two groups that deviate markedly from this pattern are bats and
      African mole-rats, with members of both groups being extremely long-lived given
      their body size, with the maximum documented lifespan for many species exceeding
      20 years. A recent genomics study of the exceptionally long-lived Brandt's bat,
      Myotis brandtii (41 years), suggested that its longevity and small body size may
      be at least partly attributed to key amino acid substitutions in the
      transmembrane domains of the receptors of growth hormone (GH) and insulin-like
      growth factor 1 (IGF1). However, whereas elevated longevity is likely to be
      common across all 19 bat families, the reported amino acid substitutions were
      only observed in two closely related bat families. To test the hypothesis that an
      altered GH/IGF1 axis relates to the longevity of African mole-rats and bats, we
      compared and analysed the homologous coding gene sequences in genomic and
      transcriptomic data from 26 bat species, five mole-rats and 38 outgroup species.
      Phylogenetic analyses of both genes recovered the majority of nodes in the
      currently accepted species tree with high support. Compared to other clades, such
      as primates and carnivores, the bats and rodents had longer branch lengths. The
      single 24 amino acid transmembrane domain of IGF1R was found to be more conserved
      across mammals compared to that of GHR. Within bats, considerable variation in
      the transmembrane domain of GHR was found, including a previously unreported
      deletion in Emballonuridae. The transmembrane domains of rodents were found to be
      more conserved, with mole-rats lacking uniquely conserved amino acid
      substitutions. Molecular evolutionary analyses showed that both genes were under
      purifying selection in bats and mole-rats. Our findings suggest that while the
      previously documented mutations may confer some additional lifespan to Myotis
      bats, other, as yet unknown, genetic differences are likely to account for the
      long lifespans observed in many bat and mole-rat species.

PMID- 25065923
TI  - Properties of water as a novel stationary phase in capillary gas chromatography.
AB  - A novel method of separation that uses water as a stationary phase in capillary
      gas chromatography (GC) is presented. Through applying a water phase to the
      interior walls of a stainless steel capillary, good separations were obtained for
      a large variety of analytes in this format. It was found that carrier gas
      humidification and backpressure were key factors in promoting stable operation
      over time at various temperatures. For example, with these measures in place, the
      retention time of an acetone test analyte was found to reduce by only 44s after
      100min of operation at a column temperature of 100 degrees C. In terms of
      efficiency, under optimum conditions the method produced about 20,000 plates for
      an acetone test analyte on a 250MUm i.d.*30m column. Overall, retention on the
      stationary phase generally increased with analyte water solubility and polarity,
      but was relatively little correlated with analyte volatility. Conversely, non
      polar analytes were essentially unretained in the system. These features were
      applied to the direct analysis of different polar analytes in both aqueous and
      organic samples. Results suggest that this approach could provide an interesting
      alternative tool in capillary GC separations. 

PMID- 25065924
TI  - Rapid quantitative chiral amphetamines liquid chromatography-tandem mass
      spectrometry: method in plasma and oral fluid with a cost-effective chiral
      derivatizing reagent.
AB  - Methamphetamine is a widely abused psychostimulant containing a chiral center.
      Consumption of over-the-counter and prescription medications may yield positive
      amphetamines results, but chiral separation of l- and d-methamphetamine and its
      metabolite amphetamine can help determine whether the source was licit or
      illicit. We present the first LC-MS/MS method with precolumn derivatization for
      methamphetamine and amphetamine chiral resolution in plasma and oral fluid
      collected with the Oral-Eze((r)) and QuantisalTM devices. To 0.5mL plasma, 0.75mL
      Oral-Eze, or 1mL Quantisal specimen racemic d11-methamphetamine and amphetamine
      internal standards were added, followed by protein precipitation. Samples were
      centrifuged and supernatants loaded onto pre-conditioned Phenomenex((r)) StrataTM
      XC Polymeric Strong Cation solid phase extraction columns. After washing,
      analytes were eluted with 5% ammonium hydroxide in methanol. The eluate was
      evaporated to dryness and reconstituted in water. Derivatization was performed
      with 1-fluoro-2,4-dinitrophenyl-5-l-alanineamide (Marfey's reagent) and heating
      at 45 degrees C for 1h. Derivatized enantiomer separations were performed under
      isocratic conditions (methanol:water, 60:40) with a Phenomenex((r)) Kinetex((r))
      2.6MUm C18 column. Analytes were identified and quantified by two MRM transitions
      and their ratio on a 3200 QTrap (AB Sciex) mass spectrometer in ESI negative
      mode. In all three matrices, the method was linear for all enantiomers from 1 to
      500MUg/L, with imprecision and accuracy of <=11.3% and 85.3-108%, respectively.
      Extraction efficiencies ranged from 67.4 to 117% and matrix effects from -17.0 to
      468%, with variation always <=19.1%. Authentic plasma and OF specimens were
      collected from an IRB-approved study that included controlled Vicks((r))
      VapoInhalerTM administration. The present method is sensitive, selective,
      economic and rapid (separations accomplished in <10min), and improves
      methamphetamine result interpretation. 

PMID- 25065925
TI  - A historical appreciation of bronchopulmonary neuroendocrine neoplasia:
      resolution of a carcinoid conundrum.
AB  - In the three-quarters of a century that have elapsed since the first description
      of a bronchial carcinoid, the field has progressed from serendipitous
      radiological or bronchoscopic diagnosis to computed tomography, magnetic
      resonance imaging, and somatostatin receptor imaging identification. Similarly,
      pathologic techniques have advanced from a naive assessment of neoplasia to a
      delineation of several tumor subtypes and an understanding of the neuroendocrine
      basis of the disease process. A key unresolved question is the identification of
      the genetic and environmental activators that are responsible for the initiation
      of pulmonary neuroendocrine cell proliferation and neoplastic transformation. 

PMID- 25065926
TI  - Pathology and diagnosis of neuroendocrine tumors: lung neuroendocrine.
AB  - Neuroendocrine (NE) tumors of the lung include a spectrum from low-grade typical
      carcinoid (TC) and intermediate-grade atypical carcinoid (AC) to high-grade large
      cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC).
      Although NE lung tumors are frequently discussed together, as in this article,
      carcinoids are very different from high-grade SCLC and LCNEC. SCLC and LCNEC are
      found in heavy-smoking, older patients, whereas smoking is not strongly
      associated with carcinoid tumors. On a molecular level, SCLC and LCNEC have
      extensive genetic abnormalities, but there are few in TC and slightly more in AC.

PMID- 25065927
TI  - Clinical presentation and evaluation of neuroendocrine tumors of the lung.
AB  - Neuroendocrine tumors of the lung encompass a wide spectrum. A carcinoid tumor is
      either a central smooth endobronchial tumor or a round, well-circumscribed,
      peripheral parenchymal lesion. Distinguishing typical carcinoid tumors from
      atypical carcinoid tumors is unreliable from a limited biopsy but can be based on
      age, presentation, and node enlargement. Large cell neuroendocrine cancer
      presents similarly to most non-small cell lung cancers. Small cell lung cancer
      has a characteristic presentation, with a rapid progression of symptoms, and a
      bulky central and/or mediastinal tumor. A diagnosis is achieved by limited biopsy
      and is usually reliable. 

PMID- 25065928
TI  - Ectopic Cushing and other paraneoplastic syndromes in thoracic neuroendocrine
      tumors.
AB  - Overproduction of corticotropin by the pituitary gland or extrapituitary tumors
      leads to hypercortisolism or Cushing syndrome. Diagnosis of suspected Cushing
      syndrome involves 3 major steps: confirmation of hypercortisolism,
      differentiation between corticotropin-independent and corticotropin-dependent
      causes of Cushing syndrome, and distinction between pituitary and ectopic
      corticotropin production. A definitive diagnosis of ectopic corticotropin
      secretion requires stringent criteria, including reversal of the clinical picture
      after resection of the tumor and/or demonstration of corticotropin
      immunohistochemical staining within the tumor tissue. 

PMID- 25065929
TI  - Functional imaging evaluation in the detection, diagnosis, and histologic
      differentiation of pulmonary neuroendocrine tumors.
AB  - Pulmonary neuroendocrine tumors (pNETs) have distinct pathologic characteristics.
      Typical carcinoids are indolent neoplasms with a good prognosis, whereas atypical
      carcinoids have a less indolent behavior. Both are optimally treated with
      complete surgical excision. More aggressive pNETs often present with local
      invasion, thoracic lymph nodal metastases, and distant spread. Patients may not
      be candidates for surgical resection and are treated with chemotherapy and/or
      radiation therapy. This article examines the potential role of functional imaging
      evaluation using (18)F FDG and somatostatin analogues labeled with (68)Ga DOTA
      peptides in well-differentiated pNETs with particular attention to clinical and
      surgical implications. 

PMID- 25065930
TI  - The significance of histology: typical and atypical bronchial carcinoids.
AB  - The aim of this study is to assess in bronchial carcinoid tumors, the prognostic
      factors in relation to the histology that would determine their most appropriate
      therapy. The histologic aggressiveness is a determining factor in tumor size and
      nodal involvement in these tumors. The knowledge of the histologic limits of
      typical and atypical carcinoid contributes to the recognition of a better
      valuation of the proportional significance that nodal involvement and histologic
      grade have in a tumor's prognosis. 

PMID- 25065931
TI  - Bronchoplastic procedures for carcinoid tumors.
AB  - Carcinoid tumors are rare lung neoplasms. They may arise centrally or
      peripherally. For central lesions, bronchoplastic procedures, particularly sleeve
      resections, are safe and should be the reference for treatment when anatomically
      and oncologically indicated, independently from pulmonary function. 

PMID- 25065932
TI  - Large-cell neuroendocrine carcinoma of the lung: surgical management.
AB  - Large-cell neuroendocrine carcinoma (LCNEC) of the lung is an uncommon aggressive
      neoplasm with a poor prognosis compared with non-small-cell lung carcinoma
      (NSCLC). Because of its rarity, the treatment recommendations are not based on
      clinical trials, but are extrapolated from the approach to patients with NSCLC
      and small-cell lung carcinoma and the established literature for LCNEC, which is
      primarily retrospective in nature. Further studies should clarify the histology
      specific characteristic and optimal therapeutic approach to establish the entity
      of LCNEC. 

PMID- 25065933
TI  - Neuroendocrine tumors of the lung: the role of surgery in small cell lung cancer.
AB  - The role of surgery in the management of patients with SCLC remains
      controversial. Although 2 randomized studies have failed to show any benefit on
      survival by adding surgery to chemotherapy, retrospective and prospective reports
      showed that surgery offers a reasonable overall survival in a subset of patients
      with stage I and II SCLC. Patients' selection is fundamental, and it should
      include extensive radiologic staging and mediastinal lymph-node biopsy. The use
      of a PET scan is likely to improve the accuracy of staging. Through primary
      surgery or after induction chemotherapy, a complete tumor resection associated
      with systematic lymphadenectomy should be achieved. 

PMID- 25065934
TI  - Thymic neuroendocrine tumors.
AB  - Thymic neuroendocrine tumors are rare and account for approximately 2% to 5% of
      all thymic tumors. Despite the suggestion of benign behavior implied by their
      name, thymic carcinoids have been noted to present a more aggressive biologic
      behavior than their counterparts in other sites. Because of the lack of data,
      adequate-sized prospective trials are required for validation, and the enrollment
      of patients with advanced disease into available clinical trials is encouraged. 

PMID- 25065935
TI  - Peptide receptor radionuclide therapy for advanced neuroendocrine tumors.
AB  - Peptide receptor radionuclide therapy (PRRT) consists of the systemic
      administration of a synthetic peptide, labeled with a suitable beta-emitting
      radionuclide, able to irradiate tumors and their metastases via internalization
      through a specific receptor (usually somatostatin S2), over-expressed on the cell
      membrane. After almost 2 decades of experience, PRRT, with either (90)Y
      octreotide or (177)Lu-octreotate, has established itself to be an efficient and
      effective therapeutic modality. As a treatment, it is relatively safe up to the
      known thresholds of absorbed and bio-effective isotope dosages and the renal and
      hematological toxicity profiles are acceptable if adequate protective measures
      are undertaken. 

PMID- 25065936
TI  - Medical treatment of advanced thoracic neuroendocrine tumors.
AB  - Thoracic Neuroendocrine Tumors (TNETs) range from the more indolent behavior of
      the well-differentiated to the highly aggressive poorly differentiated forms. A
      clinical approach totally different in terms of diagnosis and treatment is
      therefore required. Chemotherapy and radiotherapy are the treatments of choice in
      poorly differentiated, whereas biological and target therapy, peptide receptor
      radionuclide therapy (PPRT) and temozolomide have shown efficacy in small series
      or in the subgroup analysis of larger trials in well differentiated. However, no
      specific trials have been performed before this year. The first large,
      prospective, randomized trial (LUNA trial) entirely dedicated to TNET is ongoing
      at the time of this publication. 

PMID- 25065937
TI  - Knowledge of pulmonary neuroendocrine tumors: where are we now?

PMID- 25065938
TI  - Plasma Pentraxin 3 as a biomarker of metabolic syndrome.
AB  - OBJECTIVE: To assess the plasma Pentraxin 3 (PTX3) concentrations in obese
      children and to investigate the relationship between PTX3 levels and metabolic
      syndrome (MS) components. METHODS: Seventy-seven obese patients aged 10-16 y (38
      girls, 39 boys) were included in the study. PTX3 levels were compared between the
      groups with or without MS. In addition, PTX3 was analysed separately by subgroups
      according to the presence of specific MS components. RESULTS: Plasma PTX3
      concentrations were significantly higher in obese children and adolescents with
      metabolic syndrome than in those without MS (2.1 +/- 1.2 ng/ml and 1.4 +/- 0.9
      ng/ml respectively; P = 0.02). Patients with low HDL levels (<40 mg/dl) had
      higher plasma PTX3 concentrations than those with normal HDL levels (P = 0.05).
      Similarly, those who had high triglyceride levels (>= 150 mg/dl) had higher PTX3
      levels (P = 0.01). PTX3 levels were negatively correlated with HDL cholesterol (r
      = -0.32, P = 0.003) among all patients. CONCLUSIONS: PTX3 levels are higher in
      obese children and adolescents with metabolic syndrome than in those without MS.
      Thus, PTX3 levels might be a useful biomarker for children and adolescents with
      metabolic syndrome, dyslipidemia, and cardiovascular risks.

PMID- 25065939
TI  - Immortalization of T-cells is accompanied by gradual changes in CpG methylation
      resulting in a profile resembling a subset of T-cell leukemias.
AB  - We have previously described gene expression changes during spontaneous
      immortalization of T-cells, thereby identifying cellular processes important for
      cell growth crisis escape and unlimited proliferation. Here, we analyze the same
      model to investigate the role of genome-wide methylation in the immortalization
      process at different time points pre-crisis and post-crisis using high-resolution
      arrays. We show that over time in culture there is an overall accumulation of
      methylation alterations, with preferential increased methylation close to
      transcription start sites (TSSs), islands, and shore regions. Methylation and
      gene expression alterations did not correlate for the majority of genes, but for
      the fraction that correlated, gain of methylation close to TSS was associated
      with decreased gene expression. Interestingly, the pattern of CpG site
      methylation observed in immortal T-cell cultures was similar to clinical T-cell
      acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator
      phenotype positive. These sites were highly overrepresented by polycomb target
      genes and involved in developmental, cell adhesion, and cell signaling processes.
      The presence of non-random methylation events in in vitro immortalized T-cell
      cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites
      with a possible role in malignant hematopoiesis. 

PMID- 25065941
TI  - A new Rhodamine B-based 'on-off' chemical sensor with high selectivity and
      sensitivity toward Fe(3+) and its imaging in living cells.
AB  - A new fluorescent chemosensor based on a Rhodamine B and pyrrole conjugate (RBPY)
      has been designed and synthesized. UV-vis absorption and fluorescence
      spectroscopic studies show that RBPY exhibits a high selectivity and sensitivity
      toward Fe(3+) among many other metal cations in a MeOH/H2O solution (3:2, v/v, pH
      7.10, HEPES buffer, 0.1mM) by forming a 1:1 complex with Fe(3+). Furthermore,
      results reveal that the formation of the RBPY-Fe(3+) complex is fully reversible
      in the presence of sulfide anions and could also be used as an efficient sensor
      for S(2-). Importantly, fluorescence microscopy experiments further demonstrated
      that RBPY can be utilized as a fluorescent probe for the detection of Fe(3+) in
      human liver (L-02) cells. 

PMID- 25065942
TI  - Occurrence of glycosidically conjugated 1-phenylethanol and its hydrolase beta
      primeverosidase in tea (Camellia sinensis) flowers.
AB  - A previous study found that 1-phenylethanol (1PE) was a major endogenous volatile
      compound in tea (Camellia sinensis) flowers and can be transformed to
      glycosically conjugated 1PE (1PE-Gly). However, occurrences of 1PE-Gly in plants
      remain unknown. In this study, four 1PE-Glys have been isolated from tea flowers.
      Three of them were determined as (R)-1PE beta-d-glucopyranoside ((R)-1PE-Glu),
      (S)-1PE-Glu, and (S)-1PE beta-primeveroside ((S)-1PE-Pri), respectively, on the
      basis of NMR, MS, LC-MS, and GC-MS evidence. The other one was identified as (R)
      1PE-Pri on the basis of LC-MS and GC-MS data. Moreover, these 1PE-Glys were
      chemically synthesized as the authentic standards to further confirm their
      occurrences in tea flowers. 1PE-Glu had a higher molar concentration than 1PE-Pri
      in each floral stage and organ. The ratio of (R) to (S) differed between 1PE-Glu
      and 1PE-Pri. In addition, a 1PE-Gly hydrolase beta-primeverosidase recombinant
      protein produced in Escherichia coli exhibited high hydrolysis activity toward
      (R)-1PE-Pri. However, beta-primeverosidase transcript level was not highly
      expressed in the anther part, which accumulated the highest contents of 1PE-Gly
      and 1PE. This suggests that 1PE-Gly may not be easily hydrolyzed to liberate 1PE
      in tea flowers. This study provides evidence of occurrences of 1PE-Glys in plants
      for the first time. 

PMID- 25065940
TI  - Structure-affinity relationships and pharmacological characterization of new
      alkyl-resorcinol cannabinoid receptor ligands: Identification of a dual
      cannabinoid receptor/TRPA1 channel agonist.
AB  - In our ongoing program aimed at deeply investigating the endocannabinoid system
      (ES), a set of new alkyl-resorcinol derivatives was prepared focusing on the
      nature and the importance of the carboxamide functionality. Binding studies on
      CB1 and CB2 receptors, monoacylglycerol lipase (MAGL) and fatty acid amide
      hydrolase (FAAH) showed that some of the newly developed compounds behaved as
      very potent cannabinoid receptor ligands (Ki in the nanomolar range) while,
      however, none of them was able to inhibit MAGL and/or FAAH. Derivative 11 was a
      potent CB1 and CB2 ligand, with Ki values similar to WIN 55,212, exhibiting a CB1
      and CB2 agonist profile in vitro. In the formalin test of peripheral acute and
      inflammatory pain in mice, this compound showed a weak and delayed
      antinociceptive effect against the second phase of the nocifensive response,
      exhibiting, interestingly, a quite potent transient receptor potential ankyrin
      type-1 (TRPA1) channel agonist activity. Moreover, derivative 14, characterized
      by lower affinity but higher CB2 selectivity than 11, proved to behave as a weak
      CB2 competitive inverse agonist. 

PMID- 25065943
TI  - Changes in Chinese hair growth along a full year.
AB  - OBJECTIVE: To confirm the existence of seasonal hair growth cycle among Chinese
      subjects and objectivize the seasonal effect of hair loss; the hair growth
      parameters of Chinese volunteers were followed monthly for an entire year on the
      same area of vertex. METHODS: The hair growth parameters of 41 Chinese volunteers
      (women and men), free from alopecia, were recorded monthly along an entire year
      using the phototrichogram technique. RESULTS: Results show an increased rate of
      telogen hairs (growing arrest) around August-September in the study group, as
      previously reported in European subjects albeit of a lower extent and remaining
      within the normal range of healthy head hair parameters. The possible effects of
      latitude and daylight duration are discussed. CONCLUSION: Data confirm that
      Chinese hairs present characteristics of the most developed and fast growing
      terminal fibres, as compared to other non-Asian ethnics.

PMID- 25065944
TI  - Household air pollution from wood burning in two reconstructed houses from the
      Danish Viking Age.
AB  - During 13 winter weeks, an experimental archeology project was undertaken in two
      Danish reconstructed Viking Age houses with indoor open fireplaces. Volunteers
      inhabited the houses under living conditions similar to those of the Viking Age,
      including cooking and heating by wood fire. Carbon monoxide (CO) and particulate
      matter (PM2.5 ) were measured at varying distances to the fireplace. Near the
      fireplaces CO (mean) was 16 ppm. PM2.5 (mean) was 3.40 mg/m(3) , however,
      measured in one house only. The CO:PM mass ratio was found to increase from 6.4
      to 22 when increasing the distance to the fire. Two persons carried CO sensors.
      Average personal exposure was 6.9 ppm, and from this, a personal PM2.5 exposure
      of 0.41 mg/m(3) was estimated. The levels found here were higher than reported
      from modern studies conducted in dwellings using biomass for cooking and heating.
      While this may be due to the Viking house design, the volunteer's lack of
      training in attending a fire maybe also played a role. Even so, when comparing to
      today's issues arising from the use of open fires, it must be assumed that also
      during the Viking Age, the exposure to woodsmoke was a contributing factor to
      health problems. 

PMID- 25065945
TI  - How to learn pulmonary vein isolation with a novel ablation device: learning
      curve effects using the endoscopic ablation system.
AB  - INTRODUCTION: Novel ablation devices for pulmonary vein isolation (PVI) need a
      careful evaluation of its efficacy and safety beyond clinical studies in a real
      world situation. The endoscopic ablation system (EAS) was recently approved for
      PVI in Europe. We sought to determine the safety, efficacy, and learning curve
      effects of EAS-PVI in a large volume single center. METHODS AND RESULTS: Between
      June 2010 and March 2013, all EAS guided PVI procedures were analyzed and 150
      consecutive patients were divided in tertiles (T). Clinical follow-up of 12
      months assessed freedom from atrial fibrillation (AF) using 72 hour-Holter ECG
      recordings. In total, 497 of 583 PVs (85%) were isolated by visual guidance only.
      In T 2 and T 3, visually guided PVI rates increased from 73% to 91% (P < 0.001).
      After gap mapping, 96% and 99% of all PVs were isolated in T 1-3, respectively (P
      = 0.018). Total procedure and fluoroscopy time significantly declined over time.
      All major periprocedural complications occurred in the first T. In 3 patients (2
      in 1st and 1 in 2nd T), phrenic nerve palsy was observed (2%). At 12-months
      follow-up, 103 of 133 patients (77%) remained in stable sinus rhythm without
      significant differences between Ts. CONCLUSION: With EAS even first time users
      may achieve acute PVI in a high number of patients with favorable clinical
      outcomes after 1 year. Yet, acute procedural efficacy and safety are further
      improved after passing a learning curve of 50 patients.

PMID- 25065947
TI  - Collateral outcomes in e-mental health: a systematic review of the evidence for
      added benefits of computerized cognitive behavior therapy interventions for
      mental health.
AB  - BACKGROUND: E-mental health is a growing research field and an increasing number
      of computerized cognitive behavior therapy (cCBT) interventions are available for
      numerous mental health issues. Such interventions are often claimed to have added
      benefits, or collateral outcomes, when compared with traditional delivery
      platforms. Our aim was to systematically review the evidence of the cost
      effectiveness, geographic flexibility, time flexibility, waiting time for
      treatment, stigma, therapist time, effects on help-seeking and treatment
      satisfaction of cCBT interventions for mental health. METHOD: The electronic
      databases Medline and Web of Science were searched for peer-reviewed controlled
      trials investigating collateral outcomes in computerized and internet-based CBT.
      RESULTS: The literature search identified 101 published papers (95 studies),
      which were included in this review. The results suggest that cCBT interventions
      are cost-effective and often cheaper than usual care. Limited evidence was found
      with regard to geographic flexibility, time flexibility, waiting time for
      treatment, stigma and the effects on help-seeking. Personal support in cCBT was
      found to take many forms, was not limited only to therapists, and seemed to
      increase treatment adherence and reduce attrition. Treatment satisfaction with
      cCBT was found to be high, but more research on attrition due to dissatisfaction
      is required. CONCLUSIONS: Although the results of this systematic review on the
      collateral outcomes provide support for the potential of cCBT, these outcomes
      need to be better assessed within individual e-mental health studies.

PMID- 25065948
TI  - Ni12P5 nanoparticles as an efficient catalyst for hydrogen generation via
      electrolysis and photoelectrolysis.
AB  - The exploitation of a low-cost catalyst is desirable for hydrogen generation from
      electrolysis or photoelectrolysis. In this study we have demonstrated that nickel
      phosphide (Ni12P5) nanoparticles have efficient and stable catalytic activity for
      the hydrogen evolution reaction. The catalytic performance of Ni12P5
      nanoparticles is favorably comparable to those of recently reported efficient
      nonprecious catalysts. The optimal overpotential required for 20 mA/cm(2) current
      density is 143 +/- 3 mV in acidic solution (H2SO4, 0.5 M). The catalytic activity
      of Ni12P5 is likely to be correlated with the charged natures of Ni and P. Ni12P5
      nanoparticles were introduced to silicon nanowires, and the power conversion
      efficiency of the resulting composite is larger than that of silicon nanowires
      decorated with platinum particles. This result demonstrates the promising
      application potential of metal phosphide in photoelectrochemical hydrogen
      generation. 

PMID- 25065946
TI  - Artemisia annua L.: evidence of sesquiterpene lactones' fraction antinociceptive
      activity.
AB  - BACKGROUND: Artemisia annua L. has been used for many centuries in Chinese
      traditional medicine. Artemisinin, the active principle was first isolated and
      identified in the 1970s becoming the global back bone to the fight against
      malaria. Our research group previously developed an economic and ecological
      friendly process to obtain this compound. In the pursuit to also exploit the
      residue generated throughout the process we further evaluated the pharmacological
      potential of that extract. METHODS: The alcoholic crude extract after artemisinin
      precipitation maintained an enriched sesquiterpene lactones content with residue
      artemisinin (1.72%) and deoxyartemisinin (0.31%), used as chemical markers for
      this sample. This study evaluated the pharmacological potential of the enriched
      sesquiterpene lactone fraction (Lac-FR) on different nociceptive and inflammatory
      experimental animal models. Previous findings on the biological properties of
      lactones obtained from natural products permitted us to explore the
      antinociceptive activities of these compounds based on in vivo chemical-induced
      behavioral assays. RESULTS: The enriched sesquiterpene lactone fraction (Lac-FR)
      was administrated by intraperitoneal injection producing a relevant reduction in
      the reaction time of the animals in both phases of the formalin test,
      significantly reduced the sensitivity to mechanical allodynia stimulus, reduced
      the paw edema caused by carrageenan injection and promoted high antinociceptive
      activity in tail flick model suggesting relationship with the opioid system.
      Further studies are being undertaken to elucidate the active components involved
      with the antinociceptive activity as well as evaluation of synergy effect that is
      seen by combination of substances that is greater than would be expected from
      consideration of individual contributions. CONCLUSION: For the first time,
      results presented herein provided consistent data to support the potential use of
      these lactones for pain relief as revealed by chemical-induced nociception assays
      in mice.

PMID- 25065949
TI  - Outcome following intracranial hemorrhage associated with novel oral
      anticoagulants.
AB  - The emergence of dabigatran, rivaroxaban and apixaban has changed the approach to
      anticoagulation for patients worldwide. Continued approval of novel oral
      anticoagulants (NOAC) for non-valvular atrial fibrillation and venous
      thromboembolism will result in increasing use of these medications over warfarin.
      Morbidity and mortality of anticoagulant related intracranial hemorrhage (ICH) is
      relatively high and there is concern that outcomes may be worse with NOAC as
      there is a lack of specific antidotes for these agents with a greater risk for
      hematoma expansion. Unfortunately, the evidence supporting effective reversal
      strategies is lacking. Therefore, to gain further insight into the outcome after
      the management of NOAC related ICH, we present our experience with two patients
      with NOAC-induced ICH. 

PMID- 25065950
TI  - Time interval to surgery and outcomes following the surgical treatment of acute
      traumatic subdural hematoma.
AB  - Although the pre-surgical management of patients with acute traumatic subdural
      hematoma prioritizes rapid transport to the operating room, there is conflicting
      evidence regarding the importance of time interval from injury to surgery with
      regards to outcomes. We sought to determine the association of surgical timing
      with outcomes for subdural hematoma. A retrospective review was performed of 522
      consecutive patients admitted to a single center from 2006-2012 who underwent
      emergent craniectomy for acute subdural hematoma. After excluding patients with
      unknown time of injury, penetrating trauma, concurrent cerebrovascular injury,
      epidural hematoma, or intraparenchymal hemorrhage greater than 30 mL, there
      remained 45 patients identified for analysis. Using a multiple regression model,
      we examined the effect of surgical timing, in addition to other variables on in
      hospital mortality (primary outcome), as well as the need for tracheostomy or
      gastrostomy (secondary outcome). We found that increasing injury severity score
      (odds ratio [OR] 1.146; 95% confidence interval [CI] 1.035-1.270; p=0.009) and
      age (OR1.066; 95%CI 1.006-1.129; p=0.031) were associated with in-hospital
      mortality in multivariate analysis. In this model, increasing time to surgery was
      not associated with mortality, and in fact had a significant effect in decreasing
      mortality (OR 0.984; 95%CI 0.971-0.997; p=0.018). Premorbid aspirin use was
      associated with a paradoxical decrease in mortality (OR 0.019; 95%CI 0.001-0.392;
      p=0.010). In this patient sample, shorter time interval from injury to surgery
      was not associated with better outcomes. While there are potential confounding
      factors, these findings support the evaluation of rigorous preoperative
      resuscitation as a priority in future study.

PMID- 25065951
TI  - Long term outcome of Gamma Knife radiosurgery for metastatic brain tumors.
AB  - Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) has emerged as an
      important treatment option for metastatic brain tumors (MBT). However, the long
      term outcome of GKRS on MBT is not well understood. We reviewed the treatment of
      MBT with GKRS at our institution. We performed a retrospective review (2000-2013)
      of 298 patients with MBT who received GKRS. The study population was monitored
      clinically and radiographically after GKRS treatment. Survival benefits and
      predictive factors of the outcome were analyzed using the Kaplan-Meier test and
      Cox regression model, respectively. GKRS in MBT showed significant variation in
      tumor growth control (decreased in 135 [45%] patients, arrested growth in 91
      [37%] patients and increased tumor size in 72 [24%] patients). The median
      survival in the study population was 17 months. Overall and progression free
      survival after 3 years were 25% and 45%, respectively. The predictive factors for
      improving survival in the patients with MBT were recursive partitioning analysis
      class I (p<0.0001), absence of hydrocephalus (p<0.0001), Karnofsky Performance
      Status (KPS) >80 (p=0.007) and absence of recurrent MBT (p=0.01). Forty (12%), 15
      (4.3%) and two (0.6%) patients required GKRS, resection and whole brain
      radiation, respectively, after initial GKRS due to tumor progression and
      worsening of signs and symptoms. Our findings revealed that GKRS offers a high
      rate of tumor control and good survival benefits in both new and recurrent
      patients with MBT. Thus, GKRS is an effective treatment option for new patients
      with MBT, as well as an adjuvant therapy in patients with recurrent MBT.

PMID- 25065952
TI  - Copper(I)-catalyzed regioselective addition of nucleophilic silicon across
      terminal and internal carbon-carbon triple bonds.
AB  - The copper(I) alkoxide-catalyzed release of a silicon-based cuprate reagent from
      a silicon-boron pronucleophile is applied to the addition across carbon-carbon
      triple bonds. Commercially available CuBr?Me2S was found to be a general
      precatalyst that secures high regiocontrol for both aryl- and alkyl-substituted
      terminal as well as internal alkynes. The solvent greatly influences the
      regioisomeric ratio, favoring the linear regioisomer with terminal acceptors.
      This facile protocol even allows for the transformation of internal acceptors
      with remarkable levels of regio- and diastereocontrol.

PMID- 25065953
TI  - Phylogeography of Chinese house mice (Mus musculus musculus/castaneus):
      distribution, routes of colonization and geographic regions of hybridization.
AB  - House mice (Mus musculus) are human commensals and have served as a primary model
      in biomedical, ecological and evolutionary research. Although there is detailed
      knowledge of the biogeography of house mice in Europe, little is known of the
      history of house mice in China, despite the fact that China encompasses an
      enormous portion of their range. In the present study, 535 house mice caught from
      29 localities in China were studied by sequencing the mitochondrial D-loop and
      genotyping 10 nuclear microsatellite markers distributed on 10 chromosomes.
      Phylogenetic analyses revealed two evolutionary lineages corresponding to Mus
      musculus castaneus and Mus musculus musculus in the south and north,
      respectively, with the Yangtze River approximately representing the boundary.
      More detailed analyses combining published sequence data from mice sampled in
      neighbouring countries revealed the migration routes of the two subspecies into
      China: M. m. castaneus appeared to have migrated through a southern route (Yunnan
      and Guangxi), whereas M. m. musculus entered China from Kazakhstan through the
      north-west border (Xinjiang). Bayesian analysis of mitochondrial sequences
      indicated rapid population expansions in both subspecies, approximately 4650-9300
      and 7150-14 300 years ago for M. m. castaneus and M. m. musculus, respectively.
      Interestingly, the migration routes of Chinese house mice coincide with the
      colonization routes of modern humans into China, and the expansion times of house
      mice are consistent with the development of agriculture in southern and northern
      China, respectively. Finally, our study confirmed the existence of a hybrid zone
      between M. m. castaneus and M. m. musculus in China. Further study of this hybrid
      zone will provide a useful counterpart to the well-studied hybrid zone between M.
      m. musculus and Mus musculus domesticus in central Europe.

PMID- 25065954
TI  - A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial
      stress in irritable bowel syndrome.
AB  - BACKGROUND: Despite stress being considered a key factor in the pathophysiology
      of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS),
      there is a paucity of information regarding the ability of IBS patients to
      respond to acute experimental stress. Insights into the stress response in IBS
      could open the way to novel therapeutic interventions. To this end, we assessed
      the response of a range of physiological and psychological parameters to the
      Trier Social Stress Test (TSST) in IBS. METHOD: Thirteen female patients with IBS
      and 15 healthy female age-matched control participants underwent a single
      exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin
      conductance level (SCL), GI symptoms, mood and self-reported stress were measured
      pre- and post-exposure to the TSST. RESULTS: The hypothalamic-pituitary-adrenal
      (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total
      cortisol output throughout (p = 0.035) and higher cortisol levels measured by an
      area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS
      patients, GI symptoms increased significantly during the recovery period
      following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed
      significant changes in relation to stress but with no differential effect between
      experimental groups. CONCLUSIONS: Patients with IBS exhibit sustained HPA axis
      activity, and an increase in problematic GI symptoms in response to acute
      experimental psychosocial stress. These data pave the way for future
      interventional studies aimed at identifying novel therapeutic approaches to
      modulate the HPA axis and GI symptom response to acute psychosocial stress in
      IBS.

PMID- 25065955
TI  - The role of oxytocin in empathy to the pain of conflictual out-group members
      among patients with schizophrenia.
AB  - BACKGROUND: Oxytocin (OT) is associated with our ability to empathize and has
      been shown to play a major role in mediating social behaviors within the context
      of intergroup dynamics. Schizophrenia is associated with impaired empathy, and
      with a dysfunctional oxytocinergic system. The effect of OT on the empathic
      responses of patients with schizophrenia within the context of intergroup
      relationships has not been studied. The present study examined the effect of OT
      on the patients' empathic responses to pain experienced by in-group, conflictual
      out-group and neutral out-group members. METHOD: In a double-blind, placebo
      controlled, within-subject cross-over design, the responses on the Pain
      Evaluation Task of 28 male patients with schizophrenia were compared to 27
      healthy male controls. All participants received a single intranasal dose of 24
      IU OT or placebo, 1 week apart. RESULTS: OT induced an empathy bias in the
      healthy controls towards the conflictual out-group members. Although this effect
      was absent in the patient group, OT seems to heighten an empathic bias in the
      patient group towards the in-group members when rating non-painful stimuli.
      CONCLUSIONS: The study demonstrates that the administration of OT can result in
      empathic bias towards adversary out-group members in healthy controls but not in
      patients with schizophrenia. However, the OT-induced bias in both the patients
      (in the no-pain condition towards the in-group members) and the healthy controls
      (in the no-pain and pain conditions towards the adversary out-group) suggests
      that OT enhances the distinction between conflictual in-group and out-group
      members.

PMID- 25065956
TI  - Liquid-phase enantioselective chromatographic resolution using interpenetrated,
      homochiral framework materials.
AB  - Effective separation of mixtures of enantiomers is of continuing interest in
      analytical and preparative chromatography, with new materials frequently designed
      and tested. We report two new enantiomerically pure 2D->3D interpenetrated
      materials used as stationary liquid chromatographic (LC) phases that are shown to
      resolve selected racemic mixtures with enantiomeric and chemical selectivity.
      Dicarboxylate ligands derived from amino acids on naphthalene and perylene cores
      form 2D frameworks that interpenetrate to give 3D structures. Selectivity is
      initially tested by uptake from solution; subsequent LC methods show that the
      materials exhibit resolution of racemic analytes in 'micro-columns' and that the
      two closely related materials show markedly different selectivity for different
      analytes with much greater activity than the ligands alone. Comparison with a
      close-packed analogue suggests that the separation activity is largely due to
      surface effects. 

PMID- 25065957
TI  - A self-replicating peptide nucleic acid.
AB  - While the non-enzymatic ligation and template-directed synthesis of peptide
      nucleic acids (PNA) have been reported since 1995, a case of self-replication of
      PNA has not been achieved yet. Here, we present evidence for autocatalytic
      feedback in a template directed synthesis of a self-complementary hexa-PNA from
      two trimeric building blocks. The course of the reaction was monitored in the
      presence of increasing initial concentrations of the product by RP-HPLC. Kinetic
      modeling with the SimFit program revealed parabolic growth characteristics. The
      observed template effect, as well as the rate of ligation, was significantly
      influenced by nucleophilic catalysts, pH value, and uncharged co-solvents.
      Systematic optimization of the reaction conditions allowed us to increase the
      autocatalytic efficiency of the system by two orders of magnitude. Our findings
      contribute to the hypothesis that PNA may have served as a primordial genetic
      molecule and was involved in a potential precursor of a RNA world. 

PMID- 25065958
TI  - Pragmatic design in randomized controlled trials.
AB  - At more than 10 years after the paper by Hotopf and colleagues regarding
      pragmatic trials in psychiatry, the field has evolved and is evolving further.
      There have been many developments in our understanding of what pragmatism really
      means, and excellent examples of truly pragmatic trials in psychiatry are
      currently available. Funders have helped encourage more emphasis on the need for
      such studies, but 'local' and trans-national regulations could help more.
      Consumers of the evidence should have a greater voice in generating the research
      agenda and, as this happens, the questions generated are more likely to be
      answered by a pragmatic approach to trials.

PMID- 25065960
TI  - Cost-effectiveness analysis of sofosbuvir plus peginterferon/ribavirin in the
      treatment of chronic hepatitis C virus genotype 1 infection.
AB  - BACKGROUND: Sofosbuvir, an oral NS5B nucleotide polymerase inhibitor, is
      indicated for the treatment of patients infected with hepatitis C virus (HCV).
      AIM: To evaluate the long-term health economic outcomes of sofosbuvir + pegylated
      interferon alfa/ribavirin (pegIFN/RBV) compared with current treatments in
      patients infected with HCV genotype 1 in the US. METHODS: A decision-analytic
      Markov model was developed to estimate health outcomes, number needed to treat
      and short-term and long-term economic outcomes, including incremental cost
      effectiveness ratios and cost per sustained virological response (SVR), for
      several sofosbuvir-comparator regimen pairings for a cohort of 10 000 patients.
      It considered three patient cohorts: treatment-naive, treatment-experienced and
      treatment-naive human immunodeficiency virus (HIV) co-infected. Subgroup analyses
      were conducted for treatment-naive patients with and without cirrhosis. RESULTS:
      Reductions in the incidence of new cases of liver-disease complications with
      sofosbuvir + pegIFN/RBV compared with pegIFN/RBV, boceprevir + pegIFN/RBV,
      telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV were 64-82%, 50-68%, 43-58%
      and 33-56%, respectively. Sofosbuvir + pegIFN/RBV was typically associated with
      the lowest 1-year cost per SVR. When considering the lifetime incremental cost
      per quality-adjusted life-year gained, sofosbuvir + pegIFN/RBV was the most cost
      effective treatment option assessed. Sofosbuvir + pegIFN/RBV generally dominated
      (less costly and more effective than) boceprevir + pegIFN/RBV, telaprevir +
      pegIFN/RBV and simeprevir + pegIFN/RBV. CONCLUSION: Sofosbuvir + pegIFN/RBV
      yields more favourable future health and economic outcomes than current treatment
      regimens for patients across all levels of treatment experience and cirrhosis
      stage, as well as for individuals with or without HIV co-infection.

PMID- 25065961
TI  - Development of the Parental Self-Efficacy Scale for Child Autonomy toward Minor
      Surgery (PSESCAMS): based on results of questionnaire surveys of parents raising
      children between 3 and 6 years old.
AB  - AIM: The aim of this study is to prepare the Parental Self-Efficacy Scale for
      Child Autonomy toward Minor Surgery (PSESCAMS) and verify its reliability and
      validity. METHODS: The PSESCAMS was developed based on the findings of previous
      qualitative studies on preschool children aged 3-6 years who were undergoing day
      surgery and their parents. The Generalized Self-Efficacy Scale, Maternal Self
      Accomplishment Scale (MSAS), and Japanese-language version of the State-Trait
      Anxiety Inventory A-trait subscale (STAI: A-trait) were used to examine the
      criterion-related validity of the PSESCAMS. In addition, the test-retest method
      was utilized for the PSESCAMS. RESULTS: The number of valid responses was 586. A
      principle component analysis of the PSESCAMS was conducted of 18 items,
      extracting two factors. As a result of factor analysis that assumed two factors,
      the two factors were named "self-efficacy for support related to child's
      emotional control for minor surgery" and "self-efficacy for support related to
      child's understanding of minor surgery". A structural equation model having high
      goodness of fit for the PSESCAMS was shown by a covariance structure analysis.
      The correlations between GSES, MSAS, STAI: A-trait and the PSESCAMS were r =
      0.323 (P < 0.001), r = 0.370 (P < 0.001), and r = -0.248 (P < 0.001),
      respectively. Cronbach's alpha of both the initial test and the test-retest for
      the PSESCAMS were 0.9 and the correlation between both was significant.
      CONCLUSION: The PSESCAMS consists of two categories and includes 18 items. The
      reliability and validity of the PSESCAMS were proved.

PMID- 25065962
TI  - Development of a scale measuring the job satisfaction of Japanese hospital
      nurses.
AB  - AIM: This study attempts to develop a scale measuring job satisfaction in
      Japanese hospital nurses. METHODS: The authors developed items for a new scale
      measuring job satisfaction and determined the scale's internal and external
      validity. Based on this analysis, the authors then modified the scale after
      conducting two surveys. In Survey 1, the scale was tested on 600 nurses from two
      hospitals and items were selected based on item and factor analyses. In Survey 2,
      items were further refined based on responses from 800 nurses from four
      hospitals. Using these responses, the authors determined the reliability and
      validity of the scale. RESULTS: A 37 item job satisfaction scale was developed
      through examination of internal and external validity and based on the results of
      item analysis. Through factor analysis, four factors - "positive emotions toward
      work", "appropriate support from superiors", "perceived significance in the
      workplace", and "pleasant working environment" - and 28 items were extracted. The
      cumulative contribution rate was 43.9%. Cronbach's alpha coefficient was 0.91.
      The correlations found between sense of satisfaction with work, burnout, and self
      esteem supported the scale's concurrent and construct validity. CONCLUSION: The
      authors were successful in developing a scale measuring hospital nurses' job
      satisfaction. The surveys conducted using this scale identified factors
      associated with work achievement and capability development, including "positive
      emotions toward work" and "perceived significance in the workplace", neither of
      which have been covered by existing scales.

PMID- 25065959
TI  - Transfusion-related adverse events in the Platelet Dose study.
AB  - BACKGROUND: How platelet (PLT) product characteristics such as dose, source
      (whole blood derived [WBD] vs. apheresis), storage duration, and ABO matching
      status affect the risks of transfusion-related adverse events (TRAEs) is unclear.
      Similarly, more information is needed to define how recipient characteristics
      affect the frequency of TRAEs after PLT transfusion. STUDY DESIGN AND METHODS: In
      the multicenter Platelet Dose ("PLADO") study, pediatric and adult hematology
      oncology patients with hypoproliferative thrombocytopenia were randomized to
      receive low-dose (LD), medium-dose (MD), or high-dose (HD) PLT prophylaxis for a
      pretransfusion PLT count of not more than 10 * 10(9) /L. All PLT units (apheresis
      or WBD) were leukoreduced. Post hoc analyses of PLADO data were performed using
      multipredictor models. RESULTS: A total of 5034 PLT transfusions to 1102 patients
      were analyzed. A TRAE occurred with 501 PLT transfusions (10.0%). The most common
      TRAEs were fever (6.6% of transfusions), allergic or hypersensitivity reactions
      (1.9%), and sinus tachycardia (1.8%). Patients assigned HD PLTs were more likely
      than LD or MD patients to experience any TRAE (odds ratio for HD vs. MD, 1.50;
      95% confidence interval, 1.10-2.05; three-group comparison p = 0.02). PLT source
      and ABO matching status were not significantly related to overall TRAE risk.
      Compared to a patient's first PLT transfusion, subsequent PLT transfusions were
      less likely to have a TRAE reported, primarily due to a lower risk of allergic or
      hypersensitivity reactions. CONCLUSION: The most important PLT unit
      characteristic associated with TRAEs was PLT dose per transfusion. HD PLTs may
      increase the risk of TRAEs, and LD PLTs may reduce the risk.

PMID- 25065963
TI  - Using the Interpersonal Skills tool to assess interpersonal skills of
      internationally educated nurses.
AB  - AIM: To assess interpersonal skills of internationally educated nurses (IEN)
      while interacting with standardized patients. METHODS: Participants included 52
      IEN at two community hospitals in the southwestern region of the USA.
      Standardized patients were used to create patient-nurse encounter. Seventeen
      items in four domains ("skills in interviewing and collecting information";
      "skills in counseling and delivering information"; "rapport"; and "personal
      manner") in an Interpersonal Skills (IPS) instrument were measured by a Likert
      scale 1-4 with 4 indicating the best performance. The average composite score per
      domain and scores of the 17 items were compared across the domains. RESULTS: On
      10 of the 17 items, the nurses received scores under 3. Counseling with an
      average score of 2.10 and closure with an average score of 2.44 in domain 2,
      small talk with an average score of 2.06 in domain 3, and physical exam with
      average score of 2.21 in domain 4 were below 2.5. The average composite score of
      domain 1 was 3.54, significantly higher than those of domains 2-4 (2.77, 2.81,
      and 2.71, respectively). Age was moderately related to the average score per
      domain with every 10 year increase in age resulting in a 0.1 increase in the
      average score. Sex and country of origin showed mixed results. CONCLUSION: The
      interpersonal skills of IEN in three of the four domains need improvement. Well
      designed educational programs may facilitate the improvement, especially in areas
      of small talk, counseling, closure, and physical exam. Future research should
      examine relationships between the IPS and demographics factors.

PMID- 25065964
TI  - Effect of baby oil on pruritus, sleep quality, and quality of life in
      hemodialysis patients: pretest-post-test model with control groups.
AB  - AIM: To assess the effect of baby oil on pruritus, sleep quality, and quality of
      life in hemodialysis (HD) patients. METHODS: This pretest-post-test model with
      control groups study was conducted in HD units in two different provinces in
      eastern Turkey. The study group consisted of a total of 70 patients receiving HD
      treatment who met the inclusion criteria, 35 being in the intervention group and
      35 in the control group. After the patients in both groups were informed about
      the study, they were administered a questionnaire, the Severity Scale, Visual
      Analog Scale, the Pittsburgh Sleep Quality Index, and the SF-36 Quality of Life
      Scale. Following the administration of baby oil to the patients in the
      intervention group three times a week for a period of 1 month, the same scales
      were repeated to explore their pruritic status, sleep quality, and quality of
      life. The same scales were repeated also for the patients in the control group 1
      month later but without administering any baby oil. RESULTS: When the Itch
      Severity Scale, Visual Analog Scale, Pittsburgh Sleep Quality Index, and SF-36
      Quality of Life Physical and Mental Component scores of the patients in the
      control and intervention groups before and after the intervention were compared,
      the differences in the change were found to be statistically significant in favor
      of the intervention group (P < 0.05). CONCLUSION: It was found in this study that
      administration of baby oil had positive effects on itching, quality of life, and
      sleep quality in HD patients who had itching complaints.

PMID- 25065965
TI  - Cost information of chemotherapy for cervical and endometrial cancer in Japan.
AB  - AIM: Treatment cost is one of the biggest concerns for cancer patients. Providing
      information to cancer patients about treatment cost and available financial
      support contributes to high-quality care. The aim of this study was to determine
      chemotherapy costs and other medical care expenditures for patients with cervical
      and endometrial cancer. METHODS: Data from the Diagnosis Procedure Combination
      system, which is the Japanese version of the Diagnosis-related Group system, were
      used to identify 179 patients with cervical cancer and 244 patients with
      endometrial cancer who received chemotherapy from 2008-2010 at a specialized
      cancer hospital. The costs of chemotherapy per bolus, various protocols, and
      other medical care expenditures were investigated. RESULTS: The cost per bolus of
      chemotherapeutic agents varied from Y13,804-258,906 ($US 173-3236). The total
      medical cost for each course, including supportive care and treatment for
      chemotoxic symptoms, ranged Y22,230-590,140 ($US 278-7377). Fourteen protocols
      were used in this population. Multiple regression analysis revealed that the
      factors related to the total medical care cost for cervical cancer were cost of
      chemotherapeutic agents, laboratory tests, oral medications, number of
      complications, and age. For endometrial cancer, cost of chemotherapeutic agents,
      laboratory tests, and oral medications were the factors related to the total
      medical care costs. CONCLUSION: The cost of various chemotherapy protocols and
      the total medical care was determined using the Diagnosis Procedure Combination
      system. Nurses should give the information about treatment cost and discuss the
      cost with patients to facilitate high-quality care.

PMID- 25065966
TI  - Effect of organizational factors and work environments on newly graduated nurses'
      intention to leave.
AB  - AIM: The purpose of this study was to investigate intention to leave in relation
      to organizational factors and work environments among newly graduated nurses
      (NGN). METHODS: A questionnaire was delivered to NGN (n = 762) from baccalaureate
      programs as well as diploma schools from 19 R-hospitals (R-hospitals were
      designated as "public medical institutions" by the 1951 Medical Law) in 2010.
      Spearman's rank correlation coefficients and Mann-Whitney U-test were used to
      test statistical significance. RESULTS: Only 148 questionnaires were returned for
      a return rate of 19.4%. The authors found that 8.1% of respondents had a highly
      to extremely likely desire to leave nursing. Intention to leave was significantly
      associated with Nursing Work Index total (P < 0.01), social support (P < 0.001),
      work barriers (P < 0.001), commitment to workplace (P < 0.001), job satisfaction
      (P < 0.001), and burnout (P < 0.001). Those who graduated from R-schools run by
      the R-organization had significantly positive impressions of their organizations
      and significantly lower intentions to leave compared to other graduates.
      CONCLUSION: The study results suggest that NGN intention to leave the workplace
      and nursing predict actual early intention to leave. In order to reduce burnout
      and turnover, support from colleagues and supervisors appears to be essential in
      organizational and psychosocial work environments for NGN to experience job
      satisfaction and be committed to their workplace. The results of this study also
      suggest that a longitudinal study is needed to reveal the long-term effects of
      organizational factors and work environments on NGN and how they impact role
      transition and adaptation of the NGN to professional practice roles.

PMID- 25065967
TI  - Challenges associated with delivering education to patients after heart surgery.
AB  - AIM: The aim of this report is to provide a detailed description of the
      challenges that arose throughout the implementation of an individualized patient
      education intervention delivered to patients during their home recovery following
      heart surgery. METHODS: The intervention was delivered at two points in time by
      telephone to patients following heart bypass and/or valvular replacement.
      RESULTS: The individualized patient education intervention was found to be
      effective in reducing the rate and number of complications developed during the
      first three months following hospital discharge. However, throughout the
      implementation of this intervention, specific challenges arose that included:
      onset of symptoms that interfered with intervention delivery, patient's request
      for information beyond the scope of the teaching interaction, and the need to
      provide continued support to the therapist. CONCLUSION: These challenges were
      addressed throughout the course of the study and the strategies are currently
      being implemented into the planned knowledge translation activities associated
      with this intervention.

PMID- 25065968
TI  - The journey to diagnosis in AS/axial SpA: the impact of delay.
AB  - OBJECTIVES: The aim of the present study was to conduct an in-depth exploration
      of the 'journey' to diagnosis of people with ankylosing spondylitis (AS)/axial
      spondyloarthritis (Axial SpA) to gain insights into the experience, potential
      barriers and facilitators in this process. METHODS: The present qualitative
      study, embedded within a prospective longitudinal cohort study, was located
      within an interpretive phenomenological paradigm. Ten people newly diagnosed with
      AS/axial SpA, reporting an average of 10.1 [standard deviation (SD) 7.3] years
      between experiencing symptoms and diagnosis, participated in semi-structured
      interviews. The interviews were recorded, transcribed and analysed thematically.
      Ethical approval and informed consent were obtained. RESULTS: Analysis identified
      four key themes: 'What's going on?' described the process associated with trying
      to understanding a changing body experience complicated by variability and the
      severity of back pain experienced. 'Fighting for a diagnosis' provided insights
      into the process of having to 'fight' to be believed and feeling dismissed by
      healthcare professionals. 'Being adrift' explored the negative psychological
      consequences associated with a search for a diagnosis. 'The start of a journey'
      described the relief associated with receiving a diagnosis, juxtaposed against
      emotions associated with the diagnosis of a long-term degenerative condition.
      CONCLUSIONS: The delay in diagnosis experienced may be associated with lack of
      familiarity and knowledge of AS/axial SpA in the population and in healthcare
      professionals, and creates a multiplicity of problems, including psychological
      distress. Clinicians therefore need to consider the potential impact of a
      person's 'journey to diagnosis' on clinical management once a diagnosis has been
      made.

PMID- 25065969
TI  - Therapeutic exploitation of necroptosis for cancer therapy.
AB  - Evasion of programmed cell death represents one of the hallmarks of cancers that
      contributes to tumor initiation, progression and treatment resistance. This calls
      for novel therapeutic concepts to reactivate cell death programs in human
      malignancies. Since necroptosis represents a regulated form of necrosis that is
      under the control of defined signal transduction pathways, it offers molecular
      targets for rational therapeutic intervention. Indeed, there is mounting evidence
      showing that many currently used anticancer agents can engage necroptotic
      signaling pathways and thereby elicit cell death in malignant cells. A better
      understanding of the signaling networks regulating necroptosis in cancer cells is
      expected to speed up the development of anticancer drugs for therapeutic
      exploitation of necroptosis for cancer therapy. 

PMID- 25065970
TI  - Editorial.

PMID- 25065971
TI  - [Aspiration pneumonia diagnosed by esophageal transit SPECT/CT scintigraphy].

PMID- 25065973
TI  - Pilot test of a measure to assess therapeutic distance and its association with
      client attachment and corrective experience in therapy.
AB  - OBJECTIVES: The Therapeutic Distance Scale (TDS) was developed in this project to
      assesse clients' experiences of distance versus engagement with their therapist.
      METHOD: In a survey study of 47 university clients at the "mid-stage" and 34 of
      these clients at termination, four TDS subscales were identified: Too Close, Too
      Distant, Growing Autonomy, and Growing Engagement. RESULTS: TDS subscales were
      correlated as expected with working alliance and Client Attachment to Therapist.
      As hypothesized, (i) pre-therapy attachment Avoidance was significantly
      correlated with perceptions of therapists as Too Close (but not Too Distant),
      (ii) pre-therapy Anxiety was significantly correlated with Too Distant (but not
      Too Close); furthermore, among clients who developed a secure attachment to their
      therapist, (iii) pretherapy Avoidance was significantly correlated with Growing
      Engagement; however, (iv) contrary to expectations, pre-therapy anxiety was not
      significantly associated with Growing Autonomy. CONCLUSIONS: The TDS is a
      promising measure for assessing the in-therapy corrective emotional experiences
      of clients with hyperactivating attachment (i.e. increasing autonomy) and
      deactivating attachment (i.e. increasing engagement).

PMID- 25065972
TI  - Bilateral primary renal lymphoma in a pediatric patient: staging and response
      evaluation with 18F-FDG PET/CT.
AB  - Primary renal lymphoma (PRL) is a rare disease. We here present the case of an 8
      year-old child who presented with bilateral renal masses. On biopsy, it was
      confirmed to be B-cell non-Hodgkin's lymphoma. (18)F-fluorodeoxyglucose ((18)F
      FDG) positron emission tomography-computed tomography (PET/CT) for staging
      demonstrated (18)F-FDG avid bilateral renal masses, with no other abnormal focus.
      Follow up (18)F-FDG PET/CT showed complete resolution of the disease after six
      cycles of chemotherapy. Here we have highlighted the potential role of (18)F-FDG
      PET/CT in staging and response evaluation of a patient with PRL and presented a
      brief review. 

PMID- 25065974
TI  - Rural disparities in receipt of colorectal cancer screening among adults ages 50
      64 with disabilities.
AB  - BACKGROUND: Colorectal cancer is the third leading cause of cancer deaths in the
      United States. Early detection can reduce mortality; however, only 59% of U.S.
      adults age 50 and over meet recommended colorectal cancer screening guidelines.
      Studies in the general population have observed that rural residents are less
      likely to have received colorectal cancer screening than residents of urban
      areas. OBJECTIVE: To determine whether urban/rural disparities in colorectal
      cancer screening exist among people with disabilities, similar to the disparities
      found in the general population. METHODS: We analyzed Medical Expenditure Panel
      Survey annual data files from 2002 to 2008. We conducted logistic regression
      analyses to examine the relationship between urban/rural residence and ever
      having received screening for colorectal cancer (via colonoscopy, sigmoidoscopy,
      or fecal occult blood test). RESULTS: Among U.S. adults ages 50-64 with
      disabilities, those living in rural areas were significantly less likely to have
      ever received any type of screening for colorectal cancer. The urban/rural
      difference was statistically significant regardless of whether or not we
      controlled for demographic, socioeconomic, health, and health care access
      variables. CONCLUSIONS: Disparity in screening for colorectal cancer places rural
      residents with disabilities at greater risk for late stage diagnosis and
      mortality relative to people with disabilities in urban areas. Thus, there is a
      need for strategies to improve screening among people with disabilities in rural
      areas.

PMID- 25065975
TI  - Extraction, purification, kinetic and thermodynamic properties of urease from
      germinating Pisum Sativum L. seeds.
AB  - BACKGROUND: Urease, one of the highly efficient known enzymes, catalyzes the
      hydrolysis of urea into ammonia and carbon dioxide. The present study aimed to
      extract urease from pea seeds (Pisum Sativum L). The enzyme was then purified in
      three consequence steps: acetone precipitation, DEAE-cellulose ion-exchange
      chromatography, and gel filtration chromatography (Sephacryl S-200 column).
      RESULTS: The purification fold was 12.85 with a yield of 40%. The molecular
      weight of the isolated urease was estimated by chromatography to be 269,000
      Daltons. Maximum urease activity (190 U/g) was achieved at the optimum conditions
      of 40 degrees C and pH of 7.5 after 5 min of incubation. The kinetic parameters,
      Km and Vmax, were estimated by Lineweaver-Burk fits and found to be 500 mM and
      333.3 U/g, respectively. The thermodynamic constants of activation, DeltaH, Ea,
      and DeltaS, were determined using Arrhenius plot and found to be 21.20 kJ/mol,
      23.7 kJ/mol, and 1.18 kJ/mol/K, respectively. CONCLUSIONS: Urease was purified
      from germinating Pisum Sativum L. seeds. The purification fold, yield, and
      molecular weight were determined. The effects of pH, concentration of enzyme,
      temperature, concentration of substrate, and storage period on urease activity
      were examined. This may provide an insight on the various aspects of the property
      of the enzyme. The significance of extracting urease from different sources could
      play a good role in understanding the metabolism of urea in plants.

PMID- 25065976
TI  - Effect of feeding deoiled mahua (Bassia latifolia) seed cake on the growth
      performance, digestibility and balance of nutrients in cross-bred calves during
      pre-patent period of Fasciola gigantica infection.
AB  - A study was conducted to assess the growth performance and nutrient utilization
      of cross-bred calves serially infected with Fasciola gigantica and/or
      supplemented with deoiled mahua seed cake (DMSC) during pre-patent period of
      infection. Twenty healthy cross-bred (Holstein Friesian * Haryana) male calves
      aged 6-7 months with an initial average live weight of 79.6 +/- 2.71 kg were
      divided into four treatment groups (CON, CON-INF, DMC and DMC-INF) of five
      animals each following randomized block design. DMSC was included in the
      concentrate mixture of DMC and DMC-INF groups at 100 g/kg level. Animals of
      groups CON-INF and DMC-INF were given an infection of 200 metacercariae (mc) of
      F. gigantica as serial infection dose of 50 mc twice weekly over a period of 2
      weeks. A metabolism trial at 40-49 days post-infection and growth trial of 145
      days duration were conducted. The average daily gain (ADG) and feed conversion
      ratio (FCR) were significantly (p < 0.05) lower in CON-INF group as compared to
      others. The ADG and FCR were significantly (p < 0.05) higher in DMC-INF as
      compared to CON-INF. The intake and digestibility of nutrients were not affected
      by serial infection with F. gigantica during pre-patent period. However,
      significantly (p < 0.001) higher urinary excretion and significantly (p < 0.001)
      lower nitrogen balance were observed in CON-INF group as compared to other three
      groups. The nitrogen balance was significantly (p < 0.001) improved in DMC-INF
      group as compared to CON-INF group. From the results, it may be deduced that the
      supplementation of deoiled mahua seed cake at 100 g/kg level in the concentrate
      mixture has improved the growth performance and nitrogen utilization in cross
      bred calves infected with F. gigantica. 

PMID- 25065978
TI  - Chemistry without bo(a)rders.
AB  - Note from the Editor: Science, collegiality, travel without borders. Big smiles
      and warmth. Eternally youthful vigor. When I think of Tetsuo Nozoe, these are the
      images that immediately come to mind. When I think of the Nozoe Autograph Books,
      I also think of time. For 40 years, Nozoe carried with him his autograph books
      and collected his treasures which The Chemical Record is now publishing. Vladimir
      Prelog signed first when he was 47 and signed last when he was almost 80. Derek
      Barton signed first when he was 35 and signed last when he was almost 70. Time! I
      was fascinated by Eva Wille's recommendation that we publish an essay by Eva
      Maria Tanzer, a young organic chemist with already a lifetime's experience in
      exploring chemical research in laboratories around the world. Tanzer brings to us
      a charming, even innocent perspective that embraces so much of Tetsuo Nozoe's
      ideals. We are privileged to include Tanzer's vision and her experiences in the
      collection of essays that accompany the Nozoe Autograph Books. Our contributors
      range in age and experiences, from the youthful Tanzer to the more mature
      (including myself!) as do the signatories in the autograph books. Tetsuo Nozoe
      would have beamed!--Jeffrey I. Seeman Guest Editor University of Richmond
      Richmond, Virginia 23173, USA E-mail: jseeman@richmond.edu.

PMID- 25065980
TI  - Palladium-catalyzed cascade C-H trifluoroethylation of aryl iodides and Heck
      reaction: efficient synthesis of ortho-trifluoroethylstyrenes.
AB  - A palladium-catalyzed selective C-H bond trifluoroethylation of aryl iodides has
      been explored. The reaction allows for the efficient synthesis of a variety of
      ortho-trifluoroethyl-substituted styrenes. Preliminary mechanistic studies
      indicate that the reaction might involve a key Pd(IV) intermediate, which is
      generated through the rate-determining oxidative addition of CF3CH2I to a
      palladacycle; the bulky nature of CF3CH2I influences the reactivity. Reductive
      elimination from the Pd(IV) complex then leads to the formation of the aryl
      CH2CF3 bond.

PMID- 25065979
TI  - Multinational experience with hypersensitivity drug reactions in Latin America.
AB  - BACKGROUND: Epidemiologic drug allergy data from Latin America are scarce, and
      there are no studies on specific procedures focusing on this topic in Latin
      America. OBJECTIVE: To assess the clinical characteristics and management of
      hypersensitivity drug reactions in different Latin American countries. METHODS:
      An European Network of Drug Allergy questionnaire survey was implemented in 22
      allergy units in 11 Latin American countries to report on consecutive patients
      who presented with a suspected hypersensitivity drug reaction. Each unit used its
      own protocols to investigate patients. RESULTS: Included were 868
      hypersensitivity drug reactions in 862 patients (71% of adults and elderly
      patients were women and 51% of children were girls, P = .0001). Children
      presented with less severe reactions than adults and elderly patients (P <
      .0001). Urticaria and angioedema accounted for the most frequent clinical
      presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There
      were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), beta
      lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used
      most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the
      study procedures most commonly used. A large proportion of patients were treated
      in the emergency department (62%) with antihistamines (68%) and/or
      corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis
      received epinephrine. CONCLUSION: Nonsteroidal anti-inflammatory drugs and
      antibiotics were the drugs used in at least 75% of patients. More than half the
      reactions were treated in the emergency department, whereas epinephrine was
      administered in fewer than 25% of patients with anaphylaxis. Dissemination of
      guidelines for anaphylaxis among primary and emergency department physicians
      should be encouraged.

PMID- 25065981
TI  - Intra-periaqueductal gray infusion of zeta inhibitory peptide attenuates pain
      conditioned place avoidance in rats.
AB  - Pain is a complex experience that made up of sensory, emotional and cognitive
      dimensions, and the emotional factors have an important influence on intensity of
      pain perception. The role of periaqueductal gray (PAG) in sensory component of
      pain has been extensively studied, while data about pain affect are quite
      limited. Using formalin-induced conditioned place avoidance (F-CPA) test and
      inflammatory pain model, present study investigated the effect of intra-PAG
      infusion of zeta inhibitory peptide (ZIP) on noxious stimulation induced
      aversion, and the sensory component of pain. Intra-PAG injection of ZIP is
      sufficient to disrupt pain-induced aversion, but the ZIP infusion did not change
      inflammation induced pain hypersensitivity in rats. These findings suggest that
      PAG contributes to pain-related aversion in rats, and the mechanism of pain
      emotion encoding in PAG may attribute to the activation of targets of ZIP. 

PMID- 25065977
TI  - Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing
      antibodies.
AB  - Development of strategies for induction of HIV-1 broadly neutralizing antibodies
      (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV
      1-infected individuals who make bnAbs is a key strategy for immunogen design.
      Here, we study the B cell response in a bnAb-producing individual and report
      cooperation between two B cell lineages to drive bnAb development. We isolated a
      virus-neutralizing antibody lineage that targeted an envelope region (loop D) and
      selected virus escape mutants that resulted in both enhanced bnAb lineage
      envelope binding and escape mutant neutralization-traits associated with
      increased B cell antigen drive. Thus, in this individual, two B cell lineages
      cooperated to induce the development of bnAbs. Design of vaccine immunogens that
      simultaneously drive both helper and broadly neutralizing B cell lineages may be
      important for vaccine-induced recapitulation of events that transpire during the
      maturation of neutralizing antibodies in HIV-1-infected individuals. 

PMID- 25065982
TI  - Seroprevalence of Toxoplasma gondii in domestic sheep in Belgium.
AB  - Even though infected sheep are a potential source of Toxoplasma gondii infection
      in humans, information is lacking concerning the seroprevalence of T. gondii
      infection in sheep in Belgium. We examined 3170 serum samples for anti-Toxoplasma
      IgG in sheep by total lysate antigen (TLA) enzyme-linked immunosorbent assay
      (ELISA). IgG to T. gondii was demonstrated in 87.4% of the tested sheep and in
      96.2% of the 209 tested flocks. The seroprevalences in Antwerp (65.2%) and
      Wallonia (68.6%) are statistically lower than in the other regions in Belgium
      (96.7-97.8%) (P<0.05). The present study is the first report that analyzed the
      prevalence of T. gondii infection in sheep in Belgium and confirms the high
      prevalence of Toxoplasma-specific IgG antibodies in the sheep population. 

PMID- 25065983
TI  - Outer membrane vesicles of Pasteurella multocida contain virulence factors.
AB  - Pasteurella multocida (Pm) is a gram-negative bacterium able to infect different
      animal species, including human beings. This bacterium causes economic losses to
      the livestock industry because of its high morbidity and mortality in animals. In
      this work, we report the characterization of outer membrane vesicles (OMVs)
      released into the culture medium by different Pm serogroups. Purified OMVs in the
      range of 50-300 nm were observed by electron microscopy. Serum obtained from
      chickens infected with Pm recognized several proteins from Pm OMVs. Additionally,
      rabbit antiserum directed against a secreted protease from Actinobacillus
      pleuropneumoniae recognized a similar protein in the Pm OVMs, suggesting that
      OMVs from these bacterial species contain common immunogenic proteins. OmpA, a
      multifunctional protein, was identified in OMVs from different Pm serogroups, and
      its concentration was twofold higher in OMVs from Pm serogroups B and D than in
      OMVs from other serogroups. Three outer membrane proteins were also identified:
      OmpH, OmpW, and transferrin-binding protein. Three bands of 65, 110, and 250 kDa
      with proteolytic activity were detected in Pm OMVs of serogroups A and E.
      Additionally, beta-lactamase activity was detected only in OMVs from Pm 12945
      Amp(r) (serogroup A). Pm OMVs may be involved in different aspects of disease
      pathogenesis. 

PMID- 25065986
TI  - Functional sperm testing and the role of proteomics in the evaluation of male
      infertility.
AB  - The limitations of conventional semen analysis testing in the diagnosis and
      management of male factor infertility have been well documented. A number of more
      sophisticated assays including measurements of sperm deoxyribonucleic acid (DNA)
      fragmentation rates, seminal oxidative stress, and antioxidant capacity have been
      increasingly used in the evaluation of male infertility. Moreover, in the past
      few years, tremendous advancements in the burgeoning field of sperm proteomics
      promise to revolutionize the andrologist's diagnostic armamentarium, as will be
      discussed in this review. 

PMID- 25065987
TI  - The utility of an extensive postchemotherapy staging evaluation in patients
      receiving neoadjuvant chemotherapy for bladder cancer.
AB  - OBJECTIVE: To assess the utility of an extensive restaging examination performed
      after the completion of neoadjuvant chemotherapy (NAC) but before radical
      cystectomy (RC) in the management of patients with advanced bladder cancer.
      METHODS: We studied 62 patients who underwent NAC with the intent of proceeding
      to consolidative RC. A restaging examination, including endoscopic and bimanual
      examination, as well as cross-sectional imaging of the abdomen and pelvis, was
      performed after chemotherapy. The impact of restaging on clinical management was
      determined. In patients proceeding to RC, the degree of correlation between
      clinical stage (at diagnosis vs on restaging) and pathologic stage was
      determined. RESULTS: Restaging altered the treatment course in 6 patients (9.7%)
      in whom RC was not performed because of restaging findings. An additional 56
      patients (90.3%) proceeded to RC. In these patients, compared with clinical stage
      at diagnosis, the postchemotherapy clinical stage correlated more strongly with
      pathologic stage (kappa = 0.02 vs 0.17). On multivariate analysis, diagnostic
      clinical stage was not associated with pathologic stage (P = .85), whereas
      postchemotherapy clinical stage was strongly predictive of pathologic stage (P
      <.01). CONCLUSION: An extensive restaging examination altered treatment strategy
      in a small, but clinically significant subset of patients treated with NAC for
      bladder cancer. Furthermore, restaging allowed for more accurate prediction of
      pathologic stage after RC, thereby improving assessment of patient prognosis.
      Consideration should be given to incorporating a restaging evaluation into the
      standard management paradigm for bladder cancer.

PMID- 25065988
TI  - Editorial comment.

PMID- 25065989
TI  - Reply: To PMID 25065987.

PMID- 25065990
TI  - Urologic problems in spina bifida patients transitioning to adult care.
AB  - OBJECTIVE: To identify the urologic needs of adult patients with spina bifida
      (SB) at the time of their transition from pediatric to adult care. We
      hypothesized that delays in transition to adult care would be associated with
      higher rates of active problems. METHODS: We retrospectively reviewed patients
      seen at adult dedicated SB clinics at the Universities of Utah and Minnesota from
      April 2011 to April 2012. We reviewed bladder management, urologic problems, time
      from last urologic care, and necessary interventions. RESULTS: We identified 65
      patients from these clinics with SB. The mean age was 30.6 years (standard
      deviation, 11.3). The median time since last urologic evaluation at Utah and
      Minnesota was 17 months and 12 months, respectively (range 1 month-10 years).
      Fifty-five patients (85%) reported a urologic problem at the time of their visit.
      Urinary incontinence was most common in 34 (52%), followed by recurrent urinary
      tract infection in 22 (34%), catheterization troubles in 8 (12%), and calculi in
      6 (9%). Sixty-three patients (97%) required some sort of intervention. These were
      diagnostic (cystoscopy, ultrasonography, computed tomography scan, urodynamics)
      in 50 patients (77%), surgical (urinary diversion, onabotulinum toxin A
      injection, stone surgery, and so forth) in 22 (34%), and medical (antimicrobial
      prophylaxis, bladder irrigations, anticholinergics, self-catheterization) in 16
      (25%). There was no association between longer transition times and higher rates
      of active problems. CONCLUSION: On presentation to adult SB clinics, patients had
      many active urologic problems and operative management was often needed; however,
      there was no association between longer transition times and higher rates of
      active problems.

PMID- 25065991
TI  - Editorial comment.

PMID- 25065992
TI  - Re: Sabbaghian et al.: Comparison of sperm retrieval and intracytoplasmic sperm
      injection outcome in patients with and without Klinefelter syndrome (Urology
      2014;83:107-110).

PMID- 25065993
TI  - Reply by the authors.

PMID- 25065994
TI  - Is there a demonstrated advantage to increase tamsulosin dosage in patients with
      benign prostatic hyperplasia?

PMID- 25065995
TI  - Re: Jarow JP et al.: Clinical trial design for the development of new therapies
      for non-muscle-invasive bladder cancer: report of a Food and Drug Administration
      and American Urological Association public workshop (Urology 2014;83:262-265).

PMID- 25065997
TI  - An investigation of red fox (Vulpes vulpes) and Eurasian badger (Meles meles)
      scavenging, scattering, and removal of deer remains: forensic implications and
      applications.
AB  - Within northwest Europe, especially the United Kingdom, the red fox (Vulpes
      vulpes) and the Eurasian Badger (Meles meles) are the largest wild scavengers
      capable of modifying a set of remains through scavenging. Knowledge of region
      specific and species-typical scavenging behaviors of scavengers within the crime
      scene area and surroundings can aid in more efficient and accurate
      interpretations. The scavenging behaviors of captive and wild foxes and badgers
      were recorded and compared through actualistic methods and direct observation.
      The scavenging by wild foxes and badgers of surface-deposited baits and whole
      deer (Cervus nippon; Capreolus capreolus) in a woodland was observed and
      analyzed. Wild foxes were found to scavenge deer more frequently than badgers.
      The scavenging of deer remains by foxes was also compared with forensic cases.
      The scavenging pattern and recovery distances of deer and human remains scavenged
      by foxes were similar but were potentially affected by the condition and
      deposition of a body, and the presence of clothing. 

PMID- 25065996
TI  - Reply by the authors.

PMID- 25065998
TI  - Cytotoxicity and its test methodology for a bioabsorbable nitrided iron stent.
AB  - Comprehensive assessments of the cytotoxicity of nitrided iron, a promising
      bioabsorbable metallic material, were conducted using in vitro methods.
      Extracting and standing experiments were conducted to determine the factors
      influencing the precipitation of the extract during extraction and incubation.
      The MTT method, fluorescent staining, and direct contact method were used to
      explore the in vitro cytotoxicity of nitrided iron stent extracts, nitrided iron
      foils, and their bulk corrosion products. The extracting and standing experiments
      confirmed that the extraction medium and available oxygen are crucial for
      precipitation during the extraction and incubation processes. In the MTT test,
      the extract of nitrided iron stents with a high iron ion concentration (124.11 +/
      7.55 MUg/mL) was not cytotoxic to L929 fibroblasts. Thus, the in vitro
      cytotoxicity of nitrided iron stents was actually caused by the size effect of
      corrosion particles and not the material itself. Test methodology for in vitro
      cytotoxicity of biodegradable iron-based materials was analyzed, and the results
      demonstrate that multiple methods should be combined for comprehensive evaluation
      of the cytocompatibility of bioabsorbable iron-based materials to get an
      impartial conclusion.

PMID- 25065999
TI  - Microconcentric ring electrode/injector assembly for sensitive voltammetric
      analysis in single droplets of ultrasmall volumes.
AB  - This paper describes the construction of a microring electrode concentric to an
      inner injection capillary for voltammetric determination of trace analytes in
      nanoliter- to picoliter-sized droplets. The gold microring is sandwiched between
      a pulled fused-silica capillary and borosilicate glass tubing. Compared to
      polymer-coated microring electrodes, the glass-encapsulated electrode is more
      robust and does not swell in organic solvents. Consequently, the microring
      electrode is suitable for voltammetric studies of redox-active species and their
      accompanying ion transfers between two immiscible solvents. Droplets of variable
      sizes can be conveniently dispensed from front-loaded sample plugs into an
      immiscible liquid, greatly simplifying the experimental procedure and
      facilitating analysis of samples of limited availability. The size of the
      microring and the volume of the droplet deduced from well-defined voltammograms
      correlate well with those estimated from their geometric dimensions. The thin
      layer cell behavior can be attained with well-defined voltammetric peaks and
      small capacitive current. Exhaustive electrolysis in single droplets can be
      accomplished in short times (e.g., ~85 s in a droplet of 1.42 nL at a microring
      of 11.4 MUm in radius). Anodic stripping voltammetry of Ag deposited onto the
      microring electrode resulted in a detection limit of 0.13 fmol (14 fg) of Ag(+).
      The microring electrode/injector assembly can be polished repeatedly and is
      versatile for various applications (e.g., sample plugs can also be back-loaded
      via a rotary injection valve and an HPLC pump for flow injection analysis). 

PMID- 25066000
TI  - Infection of California sea lions (Zalophus californianus) with terrestrial
      Brucella spp.
AB  - Infections with Brucella ceti and pinnipedialis are prevalent in marine mammals
      worldwide. A total of 22 California sea lions (Zalophus californianus) were
      examined to determine their exposure to Brucella spp. at San Esteban Island in
      the Gulf of California, Mexico, in June and July 2011. Although samples of blood,
      vaginal mucus and milk cultured negative for these bacteria, the application of
      rose Bengal, agar gel immunodiffusion, PCR and modified fluorescence polarization
      assays found that five animals (22.7%) had evidence of exposure to Brucella
      strains. The data also suggested that in two of these five sea lions the strains
      involved were of terrestrial origin, a novel finding in marine mammals. Further
      work will be required to validate and determine the epidemiological significance
      of this finding.

PMID- 25066001
TI  - Associations of cannabis and cigarette use with psychotic experiences at age 18:
      findings from the Avon Longitudinal Study of Parents and Children.
AB  - BACKGROUND: A clearer understanding of the basis for the association between
      cannabis use and psychotic experiences (PEs) is required. Our aim was to examine
      the extent to which associations between cannabis and cigarette use and PEs are
      due to confounding. METHOD: A cohort study of 1756 adolescents with data on
      cannabis use, cigarette use and PEs. RESULTS: Cannabis use and cigarette use at
      age 16 were both associated, to a similar degree, with PEs at age 18 [odds ratio
      (OR) 1.48, 95% confidence interval (CI) 1.18-1.86 for cannabis and OR 1.61, 95%
      CI 1.31-1.98 for cigarettes]. Adjustment for cigarette smoking frequency (OR
      1.27, 95% CI 0.91-1.76) or other illicit drug use (OR 1.25, 95% CI 0.91-1.73)
      substantially attenuated the relationship between cannabis and PEs. The
      attenuation was to a lesser degree when cannabis use was adjusted for in the
      cigarette PE association (OR 1.42, 95% CI 1.05-1.92). However, almost all of the
      participants used cannabis with tobacco, including those who classed themselves
      as non-cigarette smokers. CONCLUSIONS: Teasing out the effects of cannabis from
      tobacco is highly complex and may not have been dealt with adequately in studies
      to date, including this one. Complementary methods are required to robustly
      examine the independent effects of cannabis, tobacco and other illicit drugs on
      PEs.

PMID- 25066002
TI  - Advance directive and end-of-life care preferences among nursing home residents
      in Wuhan, China: a cross-sectional study.
AB  - OBJECTIVES: To describe Chinese nursing home residents' knowledge of advance
      directive (AD) and end-of-life care preferences and to explore the predictors of
      their preference for AD. DESIGN: Population-based cross-sectional survey.
      SETTINGS: Nursing homes (n = 31) in Wuhan, Mainland Southern China. PARTICIPANTS:
      Cognitively intact nursing home residents (n = 467) older than 60 years.
      MEASURES: Face-to-face questionnaire interviews were used to collect information
      on demographics, chronic diseases, life-sustaining treatment, AD, and other end
      of-life care preferences. RESULTS: Most (95.3%) had never heard of AD, and fewer
      than one-third (31.5%) preferred to make an AD. More than half (52.5%) would
      receive life-sustaining treatment if they sustained a life-threatening condition.
      Fewer than one-half (43.3%) chose doctors as the surrogate decision maker about
      life-sustaining treatment, whereas most (78.8%) nominated their eldest son or
      daughter as their proxy. More than half (58.2%) wanted to live and die in their
      present nursing homes. The significant independent predictors of AD preference
      included having heard of AD before (odds ratio [OR] 9.323), having definite
      answers of receiving (OR 3.433) or rejecting (OR 2.530) life-sustaining
      treatment, and higher Cumulative Illness Rating Scale score (OR 1.098).
      CONCLUSIONS: Most nursing home residents did not know about AD, and nearly one
      third showed positive attitudes toward it. AD should be promoted in mainland
      China. Education of residents, the proxy decision maker, and nursing home staff
      on AD is very important. Necessary policy support, legislation, or practice
      guidelines about AD should be made with flexibility to respect nursing home
      residents' rights in mainland China.

PMID- 25066003
TI  - Reliability and benefits of medical student peers in rating complex clinical
      skills; common mistake.

PMID- 25066004
TI  - Can a conservation-oriented scientific society remain relevant in the 21st
      century?

PMID- 25066006
TI  - Multifocal synchronous mucinous adenocarcinomas arising in congenital pulmonary
      airway malformation: a case report with molecular study.
AB  - AIMS: Congenital pulmonary airway malformation (CPAM) is a rare developmental
      anomaly of the lung. Here, we report a case of mucinous adenocarcinoma arising in
      CPAM. A 23-month-old boy underwent a thoracoscopic lobectomy of the left upper
      lobe of the lung based on a presumptive diagnosis of asymptomatic CPAM, found in
      antenatal sonogram. METHODS AND RESULTS: Histologically, the lesion was
      consistent with CPAM, Stocker type I. In addition, multiple foci ranging from
      mucinous epithelial hyperplasia to mucinous adenocarcinoma were detected. All
      lesions shared the same immunoprofile with the expression of cytokeratin (CK) 20,
      MUC5AC, and human epidermal growth factor receptor2 (HER2), but were negative for
      CK7, transcription factor 1 (TTF-1), MUC1, CDX2, BRAF (VE1) and anaplastic
      lymphoma kinase (ALK). K-RAS point mutation (G12V) was also detected in all micro
      dissected mucinous lesions but EGFR mutation was not found. All lesions were
      consistent with mucinous adenocarcinoma. The patient's clinical course has been
      uneventful during the 12-months follow-up period. CONCLUSIONS: This interesting
      case demonstrated that multiple foci in CPAM can synchronously transform into
      malignancies.

PMID- 25066005
TI  - Typhoid fever in Fiji: a reversible plague?
AB  - The country of Fiji, with a population of approximately 870 000 people, faces a
      growing burden of several communicable diseases including the bacterial infection
      typhoid fever. Surveillance data suggest that typhoid has become increasingly
      common in rural areas of Fiji and is more frequent amongst young adults.
      Transmission of the organisms that cause typhoid is facilitated by faecal
      contamination of food or water and may be influenced by local behavioural
      practices in Fiji. The Fijian Ministry of Health, with support from Australian
      Aid, hosted a meeting in August 2012 to develop comprehensive control and
      prevention strategies for typhoid fever in Fiji. International and local
      specialists were invited to share relevant data and discuss typhoid control
      options. The resultant recommendations focused on generating a clearer sense of
      the epidemiology of typhoid in Fiji and exploring the contribution of potential
      transmission pathways. Additionally, the panel suggested steps such as ensuring
      that recommended ciprofloxacin doses are appropriate to reduce the potential for
      relapse and reinfection in clinical cases, encouraging proper hand hygiene of
      food and drink handlers, working with water and sanitation agencies to review
      current sanitation practices and considering a vaccination policy targeting
      epidemiologically relevant populations.

PMID- 25066007
TI  - Identifying the core microbial community in the gut of fungus-growing termites.
AB  - Gut microbes play a crucial role in decomposing lignocellulose to fuel termite
      societies, with protists in the lower termites and prokaryotes in the higher
      termites providing these services. However, a single basal subfamily of the
      higher termites, the Macrotermitinae, also domesticated a plant biomass-degrading
      fungus (Termitomyces), and how this symbiont acquisition has affected the fungus
      growing termite gut microbiota has remained unclear. The objective of our study
      was to compare the intestinal bacterial communities of five genera (nine species)
      of fungus-growing termites to establish whether or not an ancestral core
      microbiota has been maintained and characterizes extant lineages. Using 454
      pyrosequencing of the 16S rRNA gene, we show that gut communities have
      representatives of 26 bacterial phyla and are dominated by Firmicutes,
      Bacteroidetes, Spirochaetes, Proteobacteria and Synergistetes. A set of 42 genus
      level taxa was present in all termite species and accounted for 56-68% of the
      species-specific reads. Gut communities of termites from the same genus were more
      similar than distantly related species, suggesting that phylogenetic ancestry
      matters, possibly in connection with specific termite genus-level ecological
      niches. Finally, we show that gut communities of fungus-growing termites are
      similar to cockroaches, both at the bacterial phylum level and in a comparison of
      the core Macrotermitinae taxa abundances with representative cockroach, lower
      termite and higher nonfungus-growing termites. These results suggest that the
      obligate association with Termitomyces has forced the bacterial gut communities
      of the fungus-growing termites towards a relatively uniform composition with
      higher similarity to their omnivorous relatives than to more closely related
      termites. 

PMID- 25066008
TI  - Eigenspine: computing the correlation between measures describing vertebral pose
      for patients with adolescent idiopathic scoliosis.
AB  - This paper describes the concept of eigenspine, a concept applicable for
      determining the correlation between pair-wise combinations of measures useful for
      describing the three-dimensional spinal deformities associated with adolescent
      idiopathic scoliosis. The proposed data analysis scheme is based upon the use of
      principal component analysis (PCA) and canonical correlation analysis (CCA). PCA
      is employed to reduce the dimensionality of the data space, thereby providing a
      regularization of the measurements, and CCA is employed to determine the linear
      dependence between pair-wise combinations of different measures. The usefulness
      of the eigenspine concept is demonstrated by analyzing the position and the
      rotation of all lumbar and thoracic vertebrae as obtained from 46 patients
      suffering from adolescent idiopathic scoliosis. The analysis showed that the
      strongest linear relationship is found between the lateral displacement and the
      coronal rotation of the vertebrae, and that a somewhat weaker but still strong
      correlation is found between the coronal rotation and the axial rotation of the
      vertebrae. These results are well in-line with the general understanding of
      idiopathic scoliosis. Noteworthy though is that the correlation between the
      anterior-posterior displacement and the sagittal rotation was not as strong as
      expected and that the obtained results further indicate the need for including
      the axial vertebral rotation as a measure when characterizing different types of
      idiopathic scoliosis. Apart from analyzing pair-wise correlations between
      different measures, the method is believed to be suitable for finding a maximally
      descriptive low-dimensional combination of measures describing spinal deformities
      in idiopathic scoliosis. 

PMID- 25066009
TI  - Augmented depth perception visualization in 2D/3D image fusion.
AB  - 2D/3D image fusion applications are widely used in endovascular interventions.
      Complaints from interventionists about existing state-of-art visualization
      software are usually related to the strong compromise between 2D and 3D
      visibility or the lack of depth perception. In this paper, we investigate several
      concepts enabling improvement of current image fusion visualization found in the
      operating room. First, a contour enhanced visualization is used to circumvent
      hidden information in the X-ray image. Second, an occlusion and depth color
      coding scheme is considered to improve depth perception. To validate our
      visualization technique both phantom and clinical data are considered. An
      evaluation is performed in the form of a questionnaire which included 24
      participants: ten clinicians and fourteen non-clinicians. Results indicate that
      the occlusion correction method provides 100% correctness when determining the
      true position of an aneurysm in X-ray. Further, when integrating an RGB or RB
      color-depth encoding in the image fusion both perception and intuitiveness are
      improved. 

PMID- 25066010
TI  - Factors affecting formulation characteristics and stability of ascorbic acid in
      water-in-oil creams.
AB  - OBJECTIVE: The present investigation is based on the formulation of water-in-oil
      (w/o) cream preparations of ascorbic acid (AA) at pH 4-6 using different
      emollients and humectants. METHODS: The preparations were stored in the dark at
      30 degrees C for a period of 3 months and were studied for their chemical and
      physical stability. RESULTS: The pH of the creams appeared to influence the
      stability of AA as the degradation was found to increase with an increase in pH.
      The degradation of AA in w/o creams followed an apparent first-order kinetics.
      Among all the preparations, the creams containing castor oil as emollient and
      glycerine as humectant showed highest viscosity and minimum degradation as
      compared with the creams containing other excipients. This indicated that higher
      the viscosity of the medium lower will be the degradation of AA. Citric acid (CT)
      was found to decrease the rates of degradation of AA in all the cream
      preparations. CONCLUSION: The physical mixtures of AA and CT showed no
      interaction between the two compounds by FTIR spectrometry indicating that the
      reduction in rates of degradation is due to the antioxidant activity of CT which
      protected AA to some extent from the atmospheric oxygen.

PMID- 25066011
TI  - Imaging diagnosis--duodenobiliary reflux of barium sulfate during
      esophagogastrography in a dog.
AB  - A 4-year-old Australian cattle dog presented for regurgitation, 2 months after
      duodenal resection and anastomosis for a perforated duodenal ulcer.
      Duodenobiliary reflux of barium sulfate suspension was detected during
      fluoroscopic esophagogastrography. Follow-up radiography 2 hours later
      demonstrated persistence of the barium in the gallbladder and biliary tree.
      Ultrasonography showed an open sphincter of Oddi but no other morphological
      abnormalities with the gallbladder or biliary system. No side effects or
      bloodwork abnormalities were noted. This is the first case report of
      duodenobiliary reflux of barium in a dog. The pathophysiology of this phenomenon
      and its incidence and significance in human medicine are discussed. 

PMID- 25066013
TI  - Unemotional traits predict early processing deficit for fearful expressions in
      young violent offenders: an investigation using continuous flash suppression.
AB  - BACKGROUND: Research evidence suggests that cognitive and neural mechanisms
      involved in social information processing may underlie the key aspects associated
      with the emergence of aggression and psychopathy. Despite extensive research in
      this field, it is unclear whether this deficit relates to general attentional
      problems or affects early stages of information processing. Therefore, the aim
      was to explore the link between aggression, psychopathic traits, and the early
      processing deficits in young antisocial violent offenders (YAVOs) and healthy
      controls (CTLs). METHOD: Participants were presented with rapidly changing
      Mondrian-like images in one eye, while a neutral or emotional (happy, angry,
      fearful, disgusted, surprised, sad) face was slowly introduced to the other eye.
      Participants indicated the location in which the face had appeared on the screen,
      reflecting the time when they became aware of the stimulus. The relative
      processing advantage was obtained by subtracting mean reaction times for
      emotional from neutral faces. RESULTS: The results indicated that individuals
      with higher levels of unemotional traits tended to exhibit an extensive early
      processing disadvantage for fearful facial expressions; this relationship was
      only evident in the YAVO as opposed to the CTL sample. CONCLUSIONS: These
      findings indicate that an emotion processing deficit in antisocial individuals is
      present even at the most basic levels of processing and closely related to
      certain psychopathic traits. Furthermore, this early processing deficit appears
      to be highly specific to fearful expressions, which is consistent with
      predictions made by influential models of psychopathy. The clinical significance
      and potential implications of the results are discussed.

PMID- 25066012
TI  - Photodynamic therapy vs. topical imiquimod for treatment of superficial basal
      cell carcinoma: a subgroup analysis within a noninferiority randomized controlled
      trial.
AB  - BACKGROUND: A recent noninferiority randomized controlled trial (RCT) indicated
      that imiquimod can be considered as superior to methylaminolevulinate
      photodynamic therapy (MAL-PDT) in the treatment of superficial basal cell
      carcinoma (sBCC). Knowledge of treatment effectiveness in subgroups of patients
      is of great value in clinical practice to select the most effective treatment for
      an individual patient with sBCC. OBJECTIVES: To explore whether the relative
      treatment effect of MAL-PDT and imiquimod is consistent across subgroups defined
      by patient and tumour characteristics. METHODS: Data were derived from a single
      blinded, noninferiority, multicentre RCT comparing MAL-PDT, topical imiquimod and
      fluorouracil (ISRCTN79701845). Treatment success was defined as free of tumour
      recurrence at 12-month follow-up. Subgroup analyses were performed for subgroups
      defined by sex, age, tumour location and tumour size. RESULTS: Two hundred and
      two patients received MAL-PDT and 198 received imiquimod. The superiority of
      imiquimod vs. MAL-PDT was observed in subgroups of females, sBCC on the trunk and
      large tumours with risk differences in favour of imiquimod of 18.4% [95%
      confidence interval (CI) 7.8-29.0%], 21.0% (95% CI 10.9-31.1%) and 18.9% (95% CI
      7.1-30.7%), respectively. Higher probability of treatment success for imiquimod
      vs. MAL-PDT was consistently found in all other subgroups with the exception of
      sBCC localized on the lower extremities in older patients. In the latter
      subgroup, the risk difference at the expense of imiquimod was -57.3% (95% CI 
      81.7% to -32.9%). CONCLUSIONS: Imiquimod remains the first-choice treatment for
      sBCC in terms of effectiveness. In older patients with sBCC on the lower
      extremities MAL-PDT might be preferred. Results should be interpreted carefully
      as subgroup analyses were exploratory and not driven by prior hypotheses.

PMID- 25066014
TI  - The entity of immunoglobulin A-related anaphylactic transfusion reactions is not
      evidence based.

PMID- 25066015
TI  - The anxiolytic effects of a Valerian extract is based on valerenic acid.
AB  - BACKGROUND: Valerian is commonly used for the treatment of insomnia and anxiety.
      Valerian extracts allosterically modulate GABA-A receptors and induced an
      anxiolytic activity. This activity is closely related to valerenic acid. In the
      present experiments it was investigated whether acetoxy valerenic acid may
      interfere with the anxiolytic action of valerenic acid. METHODS: Situational
      anxiety was measured using male CD-1 mice in the elevated plus maze test after
      oral administration of the test substances. In addition the body core temperature
      was measured. For the 3H-GABA binding assay dissected tissue from frontal cortex
      of male RjHan:WI rats were used. Statistical evaluation was performed by means of
      the non-parametric Kruskal-Wallies H-test, followed by the two-tailed Mann
      Whitney U-test. RESULTS: Adding of acetoxy valerenic acid abolished the
      anxiolytic action of valerenic acid. There was no effect on body core
      temperature. Moreover, the valerian extract did not show any affinity to
      benzodiazepine binding sites. CONCLUSION: The determining compound for the
      observed anxiolytic effect of the valerian extract is its content of valerenic
      acid.

PMID- 25066016
TI  - Ligand-free MCR for linking quinoxaline framework with a benzimidazole nucleus: a
      new strategy for the identification of novel hybrid molecules as potential
      inducers of apoptosis.
AB  - We report a true MCR involving the reaction of N-(prop-2-ynyl)quinoxalin-2-amine
      derivatives with 2-iodoanilines and tosyl azide in the presence of 10 mol% of CuI
      and Et3N in DMSO to afford the pre-designed hybrid molecules containing
      quinoxaline framework linked with a benzimidazole nucleus. The MCR proceeds in
      the absence of any ligand and/or lateral addition of the catalyst/base affording
      products within 30 min in good yields, some of which showed encouraging apoptosis
      inducing properties in zebrafish. 

PMID- 25066018
TI  - Endoplasmic reticulum aminopeptidase 1 function and its pathogenic role in
      regulating innate and adaptive immunity in cancer and major histocompatibility
      complex class I-associated autoimmune diseases.
AB  - Major histocompatibility complex (MHC) class I molecules present antigenic
      peptides on the cell surface to alert natural killer (NK) cells and CD8(+) T
      cells for the presence of abnormal intracellular events, such as virus infection
      or malignant transformation. The generation of antigenic peptides is a multistep
      process that ends with the trimming of N-terminal extensions in the endoplasmic
      reticulum (ER) by aminopeptidases ERAP1 and ERAP2. Recent studies have
      highlighted the potential role of ERAP1 in reprogramming the immunogenicity of
      tumor cells in order to elicit innate and adaptive antitumor immune responses,
      and in conferring susceptibility to autoimmune diseases in predisposed
      individuals. In this review, we will provide an overview of the current knowledge
      about the role of ERAP1 in MHC class I antigen processing and how its
      manipulation may constitute a promising tool for cancer immunotherapy and
      treatment of MHC class I-associated autoimmune diseases. 

PMID- 25066017
TI  - The marine toxin palytoxin induces necrotic death in HaCaT cells through a rapid
      mitochondrial damage.
AB  - Palytoxin (PLTX) is one of the most toxic algal biotoxin known so far. It
      transforms the Na(+)/K(+)-ATPase into a cationic channel inducing a massive
      intracellular Na(+) influx. However, from a mechanistic point of view, the
      features and the intracellular pathways leading to PLTX-induced cell death are
      still not completely characterized. This study on skin HaCaT keratinocytes
      demonstrates that PLTX induces necrosis since propidium iodide uptake was
      observed already after 1 h toxin exposure, an effect that was not lowered by
      toxin removal. Furthermore, necrotic-like morphological alterations were
      evidenced by confocal microscopy. Apoptosis occurrence was excluded since no
      caspases 3/7, caspase 8, and caspase 9 activation as well as no apoptotic bodies
      formation were recorded. Necrosis was preceded by a very early mitochondrial
      damage as indicated by JC-1 fluorescence shift, recorded already after 5 min
      toxin exposure. This shift was totally abolished when Na(+) and Ca(2+) ions were
      withdrawn from culture medium, whereas cyclosporine-A was ineffective, excluding
      the occurrence of a controlled biochemical response. These results clearly
      establish necrosis as the primary mechanism for PLTX-induced cell death in HaCaT
      cells. The rapidity of mitochondrial damage and the consequent irreversible
      necrosis rise serious concerns about the very fast onset of PLTX toxic effects.

PMID- 25066019
TI  - Intervention fidelity in a teacher-led program to promote physical activity in
      preschool-age children.
AB  - OBJECTIVE: To examine protocol fidelity among teachers involved in a six-month
      cluster-randomized physical activity (PA) intervention. METHODS: In 2011,
      preschools in Springfield, MA were randomized to short bouts of structured PA
      (SBS-PA, n=5) or unstructured playtime (UPA, n=5). SBS-PA provided structured PA
      in the classroom during the first 10 min of gross-motor playtime followed by 20
      min of unstructured playtime. UPA consisted of 30 min of unstructured playtime.
      All teachers (SBS-PA and UPA) received a written study protocol and 1.5h of
      training. SBS-PA also received videos to use to lead structured PA and 1.5
      additional hours of training. Study fidelity and process evaluation were assessed
      twice weekly via semi-structured questionnaire. RESULTS: Only 56.6% of SBS-PA and
      75.2% of UPA free playtimes lasted for 30 min; 86.3% of SBS-PA teachers
      implemented structured PA during the first 10 min of gross-motor playtime but
      only 67.2% delivered the intervention as instructed. Only 68.5% of SBS-PA
      teachers implemented the 20-minute unstructured playtime. SBS-PA teachers
      reported that time limitations was a major barrier in implementing the designed
      intervention. Pre-post changes in PA did not differ between groups. CONCLUSION:
      Limited fidelity to intervention protocol likely impacted study findings. Future
      studies should focus on strategies to improve adherence among intervention
      leaders.

PMID- 25066020
TI  - Ability of a mass media campaign to influence knowledge, attitudes, and behaviors
      about sugary drinks and obesity.
AB  - OBJECTIVE: We examined the impact of a mass media campaign that was designed to
      educate residents about the amount of added sugars in soda and other sugary
      drinks, as well as the health impacts of consuming such drinks. METHOD: The
      campaign was implemented in Multnomah County (Portland), Oregon in 2011 and
      included paid and unpaid media on the web, television, billboards, and transit. A
      telephone survey (n=402) measured campaign awareness, attitudes toward obesity,
      knowledge about health problems of excessive sugar, and behavioral intentions and
      behaviors around soda and sugary drink consumption. RESULTS: Nearly 80% of people
      who were aware of the media campaign intended to reduce the amount of soda or
      sugary drinks they offered to a child as a result of the campaign ads. Those who
      were aware of the campaign were more likely to agree that too much sugar causes
      health problems (97.3% vs. 85.9%). There was no significant change in self
      reported soda consumption. CONCLUSION: Media campaigns about sugary drinks and
      obesity may be effective for raising awareness about added sugars in beverages,
      increasing knowledge about health problems associated with excessive sugar
      consumption, and prompting behavioral intentions to reduce soda and sugary drink
      consumption.

PMID- 25066021
TI  - Development of [18F]afatinib as new TKI-PET tracer for EGFR positive tumors.
AB  - INTRODUCTION: Afatinib is an irreversible ErbB family blocker that was approved
      for the treatment of EGFR mutated non-small cell lung cancer in 2013. Positron
      emission tomography (PET) with fluorine-18 labeled afatinib provides a means to
      obtain improved understanding of afatinib tumor disposition in vivo. PET imaging
      with [(18)F]afatinib may also provide a method to select treatment responsive
      patients. The aim of this study was to label afatinib with fluorine-18 and
      evaluate its potential as TKI-PET tracer in tumor bearing mice. METHODS: A
      radiochemically novel coupling, using peptide coupling reagent BOP, was explored
      and optimized to synthesize [(18)F]afatinib, followed by a metabolite analysis
      and biodistribution studies in two clinically relevant lung cancer cell lines,
      xenografted in nude mice. RESULTS: A reliable [(18)F]afatinib radiosynthesis was
      developed and the tracer could be produced in yields of 17.0 +/- 2.5% calculated
      from [(18)F]F(-) and >98% purity. The identity of the product was confirmed by co
      injection on HPLC with non-labeled afatinib. Metabolite analysis revealed a
      moderate rate of metabolism, with >80% intact tracer in plasma at 45 min p.i.
      Biodistribution studies revealed rapid tumor accumulation and good retention for
      a period of at least 2 hours, while background tissues showed rapid clearance of
      the tracer. CONCLUSION: We have developed a method to synthesize [(18)F]afatinib
      and related fluorine-18 labeled 4-anilinoquinazolines. [(18)F]Afatinib showed
      good stability in vivo, justifying further evaluation as a TKI-PET tracer.

PMID- 25066023
TI  - Management of calcium channel blocker overdoses.
AB  - Calcium channel blockers (CCBs) are some of the most commonly used medications in
      clinical practice to treat hypertension, angina, cardiac arrhythmias, and some
      cases of heart failure. Recent data show that CCBs are the most common of the
      cardiovascular medications noted in intentional or unintentional overdoses.(1)
      Novel treatment approaches in the form of glucagon, high-dose insulin therapy,
      and intravenous lipid emulsion therapies have been tried and have been
      successful. However, the evidence for these are limited to case reports and case
      series. We take this opportunity to review the various treatment options in the
      management of CCB overdoses with a special focus on high-dose insulin therapy as
      the emerging choice for initial therapy in severe overdoses.

PMID- 25066022
TI  - Management of umbilical hernias in patients with ascites: development of a
      nomogram to predict mortality.
AB  - BACKGROUND: The objective of this study was to develop an easy-to-use nomogram to
      assist clinicians in predicting patient-specific mortality in this patient
      population. METHODS: American College of Surgeons National Surgical Quality
      Improvement Program participant use files were used from 2005 to 2011.
      Multivariable logistic regression was used to model 30-day postoperative
      mortality in patients with ascites who underwent umbilical hernia repair.
      RESULTS: A total of 688 patients with ascites undergoing umbilical hernia repair
      were included. There were 643 (94%) survivors and 45 (7%) mortalities. A total of
      300 (44%) patients were classified as emergent cases. Using logistic regression
      to predict 30-day mortality, preoperative Model for End-Stage Liver Disease
      score, albumin, white blood cell count, and platelet count were found to be
      significant predictors (P < .05) of mortality and were included in our model.
      CONCLUSION: We propose a nomogram to enable clinicians to better estimate
      mortality in patients with ascites undergoing umbilical hernia repair.

PMID- 25066024
TI  - Azadipyrromethene-based Zn(II) complexes as nonplanar conjugated electron
      acceptors for organic photovoltaics.
AB  - The effectiveness of new a electron acceptor for organic solar cells is
      demonstrated. The acceptor is a homoleptic zinc(II) complex of 2,6
      diphenylethynyl-1,3,7,9-tetraphenylazadipyrromethene. The high power-conversion
      efficiency obtained is attributed to the acceptor's 3D structure, which prevents
      crystallization and promotes a favourable nanoscale morphology, its high Voc ,
      and its ability to contribute to light harvesting at 600-800 nm. 

PMID- 25066025
TI  - Randomised clinical trial: Polyethylene glycol 3350 with sports drink vs.
      polyethylene glycol with electrolyte solution as purgatives for colonoscopy--the
      incidence of hyponatraemia.
AB  - BACKGROUND: Polyethylene glycol 3350 plus sports drink (PEG-SD) is a hypo-osmotic
      purgative commonly used for colonoscopy, though little safety data are available.
      AIM: To evaluate the effect of PEG-SD on serum sodium (Na) and other electrolytes
      compared with PEG-electrolyte solution (PEG-ELS). METHODS: We performed a single
      center, prospective, randomised, investigator-blind comparison of PEG-ELS to PEG
      SD in out-patients undergoing colonoscopy. Laboratories were obtained at baseline
      and immediately before and after colonoscopy. The primary endpoint was
      development of hyponatraemia (Na <135 mmol/L) the day of colonoscopy. Changes in
      electrolyte levels were computed as the difference between the lowest value on
      the day of colonoscopy and baseline. Purgative tolerance and efficacy were
      assessed. RESULTS: A total of 389 patients were randomised; 364 took purgative
      and had baseline and day of colonoscopy labs (180 PEG-SD, 184 PEG-ELS). The
      groups were well matched except for a higher fraction of women and Blacks in PEG
      ELS. Seven patients (3.9%) in PEG-SD and four patients (2.2%) in PEG-ELS
      developed hyponatraemia (OR = 1.82, 95% CI: 0.45-8.62, P = 0.376). Changes in
      electrolytes from baseline were small but significantly worse with PEG-SD for
      sodium, potassium and chloride (P = 0.001, 0.012, 0.001, respectively).
      Preparation completion, adverse events, and overall colon cleansing were similar
      between the groups, but PEG-ELS had more excellent preparations (52% vs. 30%; P =
      0.001). CONCLUSIONS: Greater, but very modest, electrolyte changes occur with PEG
      SD. Hyponatraemia is infrequent with both purgatives. A significant increase in
      hyponatraemia was not identified for PEG-SD vs. PEG-ELS, but the sample size may
      have been inadequate to identify a small, but clinically important difference.
      ClinicalTrials.gov identifier NCT01299779.

PMID- 25066027
TI  - Post-traumatic Recovery to Distress Symptoms Ratio Mediates Relations of
      Resilience Fostering Resources and Their Predictors.
AB  - A large-scale study investigated the direct and indirect effects of demographic
      predictors and traumatic experiences on resilience fostering resources following
      a war. The sample consisted of 829 Israeli adults, living in a border town, 1
      year after experiencing the 2006 war with Lebanon. Resilience was assessed by
      measures of individual and public resilience and low sense of danger. Results
      show that as hypothesized the proportion of post-traumatic recovery to post-war
      distress symptoms predicts these indices of resilience and partly mediates the
      direct links between these indices and demographic predictors (age, gender and
      economic condition) and exposure to war. Research of resilience has proposed
      several prototypical trajectories that characterize responses to potentially
      traumatic events. Our discussion suggests that these trajectories and their
      changes over time can be accounted for by the balance of post-war recovery to
      symptoms level. Copyright (c) 2014 John Wiley & Sons, Ltd. 

PMID- 25066026
TI  - A population-based longitudinal study of childhood neurodevelopmental disorders,
      IQ and subsequent risk of psychotic experiences in adolescence.
AB  - BACKGROUND: Schizophrenia has a neurodevelopmental component to its origin, and
      may share overlapping pathogenic mechanisms with childhood neurodevelopmental
      disorders (NDs). Nevertheless, longitudinal studies of psychotic outcomes among
      individuals with NDs are limited. We report a population-based prospective study
      of six common childhood NDs, subsequent neurocognitive performance and the risk
      of psychotic experiences (PEs) in early adolescence. METHOD: PEs were assessed by
      semi-structured interviews at age 13 years. IQ and working memory were measured
      between ages 9 and 11 years. The presence of six NDs (autism spectrum, dyslexia,
      dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent
      completed questionnaires at age 9 years. Linear regression calculated the mean
      difference in cognitive scores between children with and without NDs.
      Associations between NDs and PEs were expressed as odds ratios (ORs) with 95%
      confidence intervals (CIs); effects of cognitive deficits were examined.
      Potential confounders included age, gender, father's social class, ethnicity and
      maternal education. RESULTS: Out of 8220 children, 487 (5.9%) were reported to
      have NDs at age 9 years. Children with, compared with those without, NDs
      performed worse on all cognitive measures; the adjusted mean difference in total
      IQ was 6.84 (95% CI 5.00-8.69). The association between total IQ and NDs was
      linear (p < 0.0001). The risk of PEs was higher in those with, compared with
      those without, NDs; the adjusted OR for definite PEs was 1.76 (95% CI 1.11-2.79).
      IQ (but not working memory) deficit partly explained this association.
      CONCLUSIONS: Higher risk of PEs in early adolescence among individuals with
      childhood ND is consistent with the neurodevelopmental hypothesis of
      schizophrenia.

PMID- 25066028
TI  - Non-invasive assessment of adrenocortical function in captive Nile crocodiles
      (Crocodylus niloticus).
AB  - The occurrence of stress-inducing factors in captive crocodilians is a concern,
      since chronic stress can negatively affect animal health and reproduction, and
      hence production. Monitoring stress in wild crocodiles could also be beneficial
      for assessing the state of health in populations which are potentially threatened
      by environmental pollution. In both cases, a non-invasive approach to assess
      adrenocortical function as a measure of stress would be preferable, as animals
      are not disturbed during sample collection, and therefore sampling is feedback
      free. So far, however, such a non-invasive method has not been established for
      any crocodilian species. As an initial step, we therefore examined the
      suitability of two enzyme-immunoassays, detecting faecal glucocorticoid
      metabolites (FGMs) with a 11beta,21-diol-20-one and 5beta-3alpha-ol-11-one
      structure, respectively, for monitoring stress-related physiological responses in
      captive Nile crocodiles (Crocodylus niloticus). An adrenocorticotropic hormone
      (ACTH) challenge was performed on 10 sub-adult crocodiles, resulting in an
      overall increase in serum corticosterone levels of 272% above the pre-injection
      levels 5h post-injection. Saline-treated control animals (n=8) showed an overall
      increase of 156% in serum corticosterone levels 5h post-administration. Faecal
      samples pre- and post-injection could be obtained from three of the six
      individually housed crocodiles, resulting in FGM concentrations 136-380% above
      pre-injection levels, always detected in the first sample collected post
      treatment (7-15 days post-injection). FGM concentrations seem comparatively
      stable at ambient temperatures for up to 72 h post-defaecation. In conclusion,
      non-invasive hormone monitoring can be used for assessing adrenocortical function
      in captive Nile crocodiles based on FGM analysis.

PMID- 25066029
TI  - Accumulation of di(2-ethylhexyl) phthalate causes endocrine-disruptive effects in
      marine medaka (Oryzias melastigma) embryos.
AB  - Di (2-ethylhexyl) phthalate (DEHP) is extensively distributed in marine
      environments. However, limited research on the toxicological and molecular
      effects of DEHP on marine organisms has been conducted. Our study investigated
      the accumulation, elimination, and endocrine-disruptive effects of DEHP on
      embryonic marine medaka (Oryzias melastigma). The medaka embryos were
      continuously exposed to DEHP (0.01, 0.1, and 1 mg/L) or 17beta-estradiol (E2,
      0.01 mg/L) until hatching, and the newly hatched larvae were then transferred to
      clean sea water for 12 days of depuration. DEHP and E2 appeared to have no
      significant effects on the mortality and hatching rates of medaka embryos, but E2
      exposure significantly delayed the hatching. Significantly higher DEHP embryonic
      burdens were detected in the group treated with higher DEHP (0.1 and 1 mg/L) at
      10 dpf (days post fertilization). The recovered larvae showed an elimination
      tendency of DEHP during the recovery period. DEHP had no significant effects on
      the transcriptional responses of endocrine-disrupting biomarker genes in the 3
      dpf embryos. Treatment with 0.1 and 1 mg/L DEHP elicited a significant induction
      of transcriptional responses of ER, PPAR, and the CYP19 genes in a concentration
      dependent manner at 10 dpf, indicating endocrine disruption may be due to
      bioaccumulation of DEHP. With the elimination of DEHP during the depuration
      period, all of the effects on these genes showed no significant effects. However,
      0.1 mg/L E2 significantly affected the expression of ER, PPAR, and the CYP19
      genes in the exposed embryos at both 3 and 10 dpf and recovered larvae.
      Therefore, these results demonstrate that accumulation of DEHP caused endocrine
      disruption in medaka embryos and that recovery in clean sea water may weaken the
      endocrine-disrupting effects.

PMID- 25066030
TI  - Use of serological and mucosal immune responses to Mycoplasma hyopneumoniae
      antigens P97R1, P46 and P36 in the diagnosis of infection.
AB  - Currently available ELISAs used to diagnose Mycoplasma hyopneumoniae infection in
      pigs have high specificity but low sensitivity. To develop more sensitive assays,
      the kinetics of specific serum IgG and respiratory mucosal sIgA responses against
      three M. hyopneumoniae antigens, namely, P97R1 (an adhesin protein), P46 (a
      membrane protein), and P36 (a cytosolic protein), were characterised over 133
      days following experimental infection. Immunoglobulin G against the three
      proteins remained at high concentrations from 28 to 133 days post-infection
      (dpi), although IgG against P97R1 was detected earlier and was more reactive than
      the other two antigens under assessment. Mucosal sIgA appeared earlier than serum
      IgG but did not persist as long; sIgA concentrations against P97R1 were the
      highest. Seroconversion was detected 2 weeks earlier with the P97R1-based ELISA
      than with a commercially available ELISA. On analysis of serum samples from five
      pig farms that did not use a M. hyopneumoniae vaccine, the P97R1-based IgG ELISA
      demonstrated a 73.6% coincidence rate with the commercial kit. Moreover, this
      more specific P97R1-based ELISA detected more positive samples than the
      commercial kit (52.8% vs. 39.2%). It was concluded that the systemic immune
      response to M. hyopneumoniae infection in pigs was delayed in onset but
      persistent whereas the mucosal response developed more rapidly but was less
      sustained. The P97R1 antigen was identified as a suitable serological marker for
      diagnosing M. hyopneumoniae infection in pigs, particularly early stage
      infection.

PMID- 25066031
TI  - Impact of race training on volumetric bone mineral density and its spatial
      distribution in the distal epiphysis of the third metatarsal bone of 2-year-old
      horses.
AB  - The aim of the study was to use spatial and multiple correspondence analysis
      (MCA) to describe and compare the regional proportion and spatial pattern of
      volumetric bone mineral density (BMDv) values within loaded regions of the
      plantar metatarsal epiphysis of young horses in race training. A single 2 mm
      transverse peripheral quantitative computed tomography 'slice', 10 mm proximal
      from the distal limit of the sagittal ridge of the distal metatarsal epiphysis
      was obtained from 14 2-year-old Thoroughbred fillies (7 exercised and 7
      controls). Six regions of interest were generated and examined for relative BMDv
      using MCA. The spatial distribution of BMDv was statistically examined at two
      sites loaded by the proximal sesamoid bones using geographical information
      software. The BMDv response was focal with distinct regional differences in
      relation to load. Deposition of new bone within existing high density bone
      contributed to a greater bone fraction and the distinct profile of clusters of
      uniformly distributed high density bone as well as a lower proportion of lower
      density bone in exercised horses. The MCA and spatial analysis provided
      statistical techniques to quantify and describe non-invasively the exercise
      induced changes in bone that had previously been described using microradiography
      of thin slices and by block-face imaging. These statistical techniques may prove
      useful in quantifying spatial patterns of response to load.

PMID- 25066032
TI  - Establishment of a novel two-probe real-time PCR for simultaneously
      quantification of hepatitis B virus DNA and distinguishing genotype B from non-B
      genotypes.
AB  - OBJECTIVE: Establishment of a simple, rapid and economical method for
      quantification and genotyping of hepatitis B virus (HBV) is of great importance
      for clinical diagnosis and treatment of chronic hepatitis B patients. We hereby
      aim to develop a novel two-probe real-time PCR for simultaneous quantification of
      HBV viral concentration and distinguishing genotype B from non-B genotypes.
      METHODS: Conserved primers and TaqMan probes for genotype B and non-B genotypes
      were designed. The linear range, detection sensitivity, specificity and
      repeatability of the method were assessed. 539 serum samples from HBV-infected
      patients were assayed, and the results were compared with commercial HBV
      quantification and HBV genotyping kits. RESULTS: The detection sensitivity of the
      two-probe real-time PCR was 500IU/ml; the linear range was 10(3)-10(9)IU/ml, and
      the intra-assay CVs and inter-assay CVs were between 0.84% and 2.80%. No cross
      reaction was observed between genotypes B and non-B. Of the 539 detected samples,
      509 samples were HBV DNA positive. The results showed that 54.0% (275/509) of the
      samples were genotype B, 39.5% (201/509) were genotype non-B and 6.5% (33/509)
      were mixed genotype. The coincidence rate between the method and a commercial HBV
      DNA genotyping kit was 95.9% (488/509, kappa=0.923, P<0.01). In addition, high
      correlation (R(2)=0.94, P<0.05) and good consistency between our assay and a
      commercial HBV DNA qPCR kit were achieved. CONCLUSIONS: A novel two-probe real
      time PCR method for simultaneous quantification of HBV viral concentration and
      distinguishing genotype B from non-B genotypes was established. The assay was
      sensitive, specific and reproducible which can be applied to areas prevalent with
      HBV genotypes B and C, especially in China.

PMID- 25066033
TI  - Scoliosis Research Society (SRS) Criteria and Society of Scoliosis Orthopaedic
      and Rehabilitation Treatment (SOSORT) 2008 Guidelines in Non-Operative Treatment
      of Idiopathic Scoliosis.
AB  - According to the Scoliosis Research Society (SRS), idiopathic scoliosis (IS) is a
      curvature of more than 10 degrees  Cobb angle, affecting 2-3% of pediatric
      population. Idiopathic scoliosis accounts for 80% of all scoliosis cases. Non
      operative principles in the therapy of idiopathic scoliosis, including Scoliosis
      Research Society (SRS) criteria and guidelines proposed by the experts of the
      Society on Scoliosis Orthopedic and Rehabilitation Treatment (SOSORTS) were
      presented. The possibility to carry out quality of life assessments in a
      conservative procedure was also demonstrated. Based on the natural history of
      idiopathic scoliosis, SRS criteria, SOSORT 2008 experts' opinion and the
      knowledge of the possibilities of psychological assessment of conservative IS
      treatment, rules were proposed regarding nonsurgical IS therapy procedures, with
      special consideration being paid to the proper treatment start time (age, Risser
      test, biological maturity, Cobb angle), possibility of curvature progression, the
      importance of physiotherapy and psychological assessment. The knowledge of SRS
      criteria and SOSORT guidelines regarding the conservative treatment of IS are
      essential for proper treatment (the right time to start treatment), and supports
      establishment of interdisciplinary treatment teams, consisting of a physician, a
      physiotherapist, an orthopedic technician and a psychologist.

PMID- 25066034
TI  - Dietary differences are reflected on the gut prokaryotic community structure of
      wild and commercially reared sea bream (Sparus aurata).
AB  - We compared the gut prokaryotic communities in wild, organically-, and
      conventionally reared sea bream (Sparus aurata) individuals. Gut microbial
      communities were identified using tag pyrosequencing of the 16S rRNA genes. There
      were distinct prokaryotic communities in the three different fish nutritional
      treatments, with the bacteria dominating over the Archaea. Most of the Bacteria
      belonged to the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes.
      The number of bacterial operational taxonomic units (OTUs) was reduced from the
      wild to the conventionally reared fish, implying a response of the gut
      microorganisms to the supplied food and possibly alterations in food
      assimilation. The dominant bacterial OTU in all examined fish was closely related
      to the genus Diaphorobacter. This is the first time that a member of the beta
      Proteobacteria, which dominate in freshwaters, are so important in a marine fish
      gut. In total the majority of the few Archaea OTUs found, were related to methane
      metabolism. The inferred physiological roles of the dominant prokaryotes are
      related to the metabolism of carbohydrates and nitrogenous compounds. This study
      showed the responsive feature of the sea bream gut prokaryotic communities to
      their diets and also the differences of the conventional in comparison to the
      organic and wild sea bream gut microbiota. 

PMID- 25066035
TI  - Structurally tunable 3-cyanoformazanate boron difluoride dyes.
AB  - The straightforward synthesis of a series of 3-cyanoformazanate boron difluoride
      dyes is reported. Phenyl, 4-methoxyphenyl and 4-cyanophenyl N-substituted
      derivatives were isolated and characterized by single-crystal X-ray
      crystallography, cyclic voltammetry, and UV/Vis spectroscopy. The compounds were
      demonstrated to possess tunable, substituent-dependent absorption, emission, and
      electrochemical properties, which were rationalized through electronic structure
      calculations. 

PMID- 25066036
TI  - Development of multiscale models for complex chemical systems: from H+H2 to
      biomolecules (Nobel Lecture).

PMID- 25066037
TI  - Delta-like homologue 1 and its role in the bone marrow niche and hematologic
      malignancies.
AB  - Delta-like homologue 1 (DLK1) is an imprinted gene, that acts as a Notch pathway
      antagonist. It is deregulated in solid and blood cancers, conferring malignant
      cells a cancer stem cell-like phenotype. DLK1 is important for normal
      hematopoiesis and for bone marrow homeostasis, because it directly affects the
      differentiation of mesenchymal stem cells into the nonhematopoietic components.
      It is possible that the resulting abnormal biology of mesenchymal stem cells
      promotes leukemic blasts survival providing also a sanctuary against
      chemotherapeutic agents. In this review, the effects of DLK1 on mesenchymal stem
      cells and the bone marrow microenvironment with perspectives are discussed.

PMID- 25066038
TI  - Follicular lymphoma grade 3: review and updates.
AB  - Follicular lymphoma (FL), Grade 3, is recognized as a distinct entity in the
      World Health Organization classification of lymphoma. It is further classified
      into Grade 3a and Grade 3b depending on the Bernard cell counting system and
      percentage of centroblasts. Grade 3 has molecular and genetic characteristics
      that distinguish it from other grades of FL. There is confusion and
      misunderstanding about the natural history and clinical course of Grade 3a and 3b
      because some studies indicate them as having indolent behavior and others
      describe more aggressive biology. The purpose of this article is to understand
      the concept of Grade 3 FL, especially the fundamental differences between Grade
      3a and Grade 3b FL. Grade 3 FL is still an evolving subclass in FL and the
      practicing physician should understand the aggressive nature of Grade 3b, which
      typically requires timely attention, compared with Grade 3a. Grade 3a FL has more
      indolent characteristics but can possibly progress to Grade 3b and/or transform
      to diffuse large B-cell lymphoma at a future time. Nevertheless, large
      prospective studies are missing for an optimal evidence-based management approach
      for patients with Grade 3 FL at this time.

PMID- 25066039
TI  - Residual cancer lymphocytes in patients with chronic lymphocytic leukemia after
      therapy show increased expression of surface antigen CD52 detected using
      quantitative fluorescence cytometry.
AB  - BACKGROUND: Rituximab and alemtuzumab, mAbs used in recent years to treat CLL,
      are directed against antigens CD20 and CD52. CD20 is not highly expressed by CLL
      tumor cells, and rituximab does not have significant effectiveness in CLL unless
      combined with chemotherapy. Alemtuzumab targets CD52, which is much more highly
      expressed, and is currently the most effective agent used alone for CLL.
      Variability in expression of both antigens among these patients might be related
      to different individual therapeutic responses to mAb therapy. PATIENTS AND
      METHODS: A total 95 patients diagnosed with CLL and/or SLL were divided into 4
      groups: (1) untreated; (2) in complete or partial remission; (3) disease in
      progression; and (4) diagnosed with SLL. Flow cytometry of peripheral blood cells
      included gating of the CD5(+)CD19(+) tumor population, within which mean
      fluorescence intensity of fluorescein isothiocyanate (FITC) conjugated with anti
      CD20 or anti-CD52 antibody was measured. The resulting expression of the 2
      antigens was deduced from the calibration curve using Quantum FITC particles.
      RESULTS: Expression of CD20 showed no significant differences among the 4 groups
      of patients. However, significantly greater expression of surface antigen CD52
      was recorded in patient group 2 in complete or partial remission (P < .001).
      CONCLUSION: The residual population of CLL cells after therapy is characterized
      by increased surface detection of CD52. Although the exact cause of this
      phenomenon is unknown, our results provide a basis to consider the potential for
      CLL consolidation therapy using alemtuzumab.

PMID- 25066040
TI  - Identifying professional education gaps and barriers in multiple myeloma patient
      care: findings of the Managing Myeloma Continuing Educational Initiative Advisory
      Committee.
AB  - Advances in the past decade and a half have led to unprecedented improved
      outcomes for patients with multiple myeloma (MM), and this disease appears to be
      transitioning to one more characteristic of a chronic disease in large part due
      to rapid translation of clinical insights into practice at the community level.
      Although evidence-based guidelines and consensus recommendations remain an
      important resource for managing cancer patients, they do not fill the gap between
      the principles of disease management today and the translation of tailoring
      treatment for individual patient needs. Thus, there is a continuing need for
      concise, focused educational activities and resources that facilitate improved
      knowledge and understanding of appropriate, individualized therapeutic strategies
      for assessing and caring for patients with MM. The next several years will truly
      be a time of shifting paradigms in the treatment of MM in which new agents will
      be approved, response criteria will be updated, and new approaches to risk
      assessment and monitoring minimal residual disease will evolve and enter
      practice. New groundbreaking therapeutic approaches, such as immunotherapy, might
      result in significant changes in how MM is treated and managed over the entire
      life cycle of the disease. Even the definition of the disease might be further
      amended as insights grow regarding who should be treated and who might benefit
      more from observation. As such, oncology clinicians will have to carefully review
      and update their management approaches accordingly even as they begin to focus
      even more on the survivorship needs of their MM patients. 

PMID- 25066041
TI  - The development of an instrument to measure global dimensions of maternal care in
      rhesus macaques (Macaca mulatta).
AB  - One of the strongest predictors of healthy child development is the quality of
      maternal care. Although many measures of observation and self-report exist in
      humans to assess global aspects of maternal care, such qualitative measures are
      lacking in nonhuman primates. In this study, we developed an instrument to
      measure global aspects of maternal care in rhesus monkeys, with the goal of
      complementing the individual behavioral data collected using a well-established
      rhesus macaque ethogram during the first months postpartum. The 22 items of the
      instrument were adapted from human maternal sensitivity assessments and a
      maternal Q-sort instrument already published for macaques. The 22 items formed
      four dimensions with high levels of internal reliability that represented major
      constructs of maternal care: (1) Sensitivity/Responsivity, (2) Protectiveness,
      (3) Permissiveness, and (4) Irritability. These dimensions yielded high construct
      validity when correlated with mother-infant frequency and duration behavior that
      was collected from focal observations across the first 3 postnatal months. In
      addition, comparisons of two groups of mothers (Maltreating vs. Competent
      mothers) showed significant differences across the dimensions suggesting that
      this instrument has strong concurrent validity, even after controlling for focal
      observation variables that have been previously shown to significantly
      differentiate these groups. Our findings suggest that this Instrument of Macaque
      Maternal Care has the potential to capture global aspects of the mother-infant
      relationship that complement individual behaviors collected through focal
      observations.

PMID- 25066042
TI  - Ranolazine terminates atrial flutter and fibrillation in a canine model.
AB  - BACKGROUND: Ranolazine has been shown to have antiarrhythmic properties.
      OBJECTIVE: We tested the hypothesis that intravenous ranolazine would terminate
      induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile
      pericarditis model. METHODS: In 6 dogs with sterile pericarditis, we performed
      electrophysiological measurements of the atrial effective refractory period
      (AERP) and conduction time (CT) while pacing from the right atrial appendage,
      Bachmann bundle, and the posteroinferior left atrium at cycle lengths (CLs) of
      400, 300, and 200 ms before and after the administration of ranolazine. In 13
      induced episodes of AFL (n = 9) and AF (n = 4), ranolazine was administered
      intravenously as a 3.2 mg/kg bolus, followed by a maintenance infusion of 0.17
      mg/(kg.min). Six episodes (4 AFL and 2 AF) were induced in the open-chest state
      to perform simultaneous, multisite (486 electrodes), epicardial mapping of the
      arrhythmia and its termination. RESULTS: Ranolazine terminated 7 of 9 AFL and 3
      of 4 AF episodes. Ranolazine significantly prolonged the AFL CL by a mean of 43
      ms (P < .001) and the AF CL by a mean of 34 ms (P < .01). The AERP was prolonged
      (P < .05 overall), and the atrial capture threshold increased minimally (P < .01
      for all). Ranolazine prolonged CTs (P < .01 overall). During open-chest,
      multisite mapping, block in the region of slow conduction in the reentrant
      circuit terminated AFL and interruption of the regular driver terminated AF.
      CONCLUSION: Ranolazine terminated AFL/AF in our canine sterile pericarditis model
      by interrupting the regular driver. Ranolazine was found to significantly prolong
      the AERP, CT, and tachycardia CLs.

PMID- 25066043
TI  - Expression of group III metabotropic glutamate receptors in the reproductive
      system of male mice.
AB  - Although the presence of metabotropic glutamate (mGlu) receptors in the central
      nervous system is well documented, they have recently been found in peripheral
      and non-neuronal tissues. In the present study we investigated the expression of
      group III mGlu receptors in the reproductive system of male mice. Reverse
      transcription-polymerase chain reaction analysis revealed the presence of mGlu6,
      mGlu7 and mGlu8 (but not mGlu4) receptor transcripts in testes and epididymides
      from adult mice. In addition, expression of mGlu6 (Grm6) and mGlu8 receptor
      (Grm8) mRNA was detected in spermatozoa isolated from the vas deferens. The vas
      deferens was found to contain only mGlu7 receptor (Grm7) mRNA, which was
      particularly intense in 21-day-old male mice. In penile homogenates, only the
      mGlu7 receptor signal was detected. Genetic ablation of the mGlu7 receptor in
      males led to fertility disorders manifested by decreased insemination capability
      as well as deterioration of sperm parameters, particularly sperm motility,
      vitality, sperm membrane integrity and morphology, with a simultaneous increase
      in sperm concentration. These results indicate that constitutively expressed mGlu
      receptors in the male reproductive system may play an important role in
      ejaculation and/or erection processes, as well as in the formation and maturation
      of spermatozoa. 

PMID- 25066044
TI  - Clinical impact of nonsustained ventricular tachycardia recorded by the
      implantable cardioverter-defibrillator in patients with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is a risk factor for
      sudden death (SD) in hypertrophic cardiomyopathy (HCM). Implantable cardioverter
      defibrillators (ICDs) enable accurate assessment of NSVT burden and
      characteristics. In a cohort of HCM patients with ICD, we characterized Holter-
      and ICD-retrieved NSVT and evaluated their relationship with prognosis. METHODS
      AND RESULTS: We studied a cohort of consecutive HCM patients who underwent Holter
      ECG before receiving a primary prevention ICD. Patients were followed from ICD
      implantation to the first appropriate ICD therapy. We evaluated the association
      of NSVT characteristics with ICD interventions. Study cohort included 51 HCM
      patients (28 males, mean age: 48 +/- 15 years). Thirty-four patients (66%) had
      NSVT at pre-ICD Holter ECG. Out of 17 patients with negative baseline Holter, 7
      (41%) showed ICD-NSVT. In patients with both Holter- and ICD-NSVT, these latter
      were faster (199 +/- 27 bpm vs. 146 +/- 24 bpm; P < 0.001) and longer (16 +/- 8
      beats vs. 10 +/- 11 beats; P = 0.008) than Holter-NSVT. During follow-up (38 +/-
      24 months), 11 patients (22%) experienced appropriate ICD therapy. NSVT length in
      beats (hazard ratio [HR]: 1.05; 95% CI: 1.00-1.10; P = 0.02) but not heart rate
      (HR: 1.00; 95% CI: 0.98-1.02; P = 0.86) predicted ICD intervention. A simple
      index of NSVT severity (heart rate * length in beats/100 >28) predicted ICD
      intervention (HR: 5.45; 95% CI: 1.10-27.32; P = 0.03). CONCLUSIONS: Long-lasting
      and rapid NSVT recorded during continuous rhythm monitoring predict appropriate
      ICD intervention in high-risk HCM patients. Further studies should assess whether
      prolonged rhythm monitoring may assist in evaluating patients at intermediate
      risk of SD, in which the decision to implant an ICD needs to be individualized.

PMID- 25066045
TI  - Evaluation of soy-based surface active copolymers as surfactant ingredients in
      model shampoo formulations.
AB  - OBJECTIVE: A new non-toxic soybean oil-based polymeric surfactant (SBPS) for
      personal-care products was developed and extensively characterized, including an
      evaluation of the polymeric surfactant performance in model shampoo formulations.
      METHODS: To experimentally assure applicability of the soy-based macromolecules
      in shampoos, either in combination with common anionic surfactants (in this
      study, sodium lauryl sulfate, SLS) or as a single surface-active ingredient, the
      testing of SBPS physicochemical properties, performance and visual assessment of
      SBPS-based model shampoos was carried out. RESULTS: The results obtained,
      including foaming and cleaning ability of model formulations, were compared to
      those with only SLS as a surfactant as well as to SLS-free shampoos. Overall, the
      results show that the presence of SBPS improves cleaning, foaming, and
      conditioning of model formulations. CONCLUSIONS: SBPS-based formulations meet
      major requirements of multifunctional shampoos - mild detergency, foaming, good
      conditioning, and aesthetic appeal, which are comparable to commercially
      available shampoos. In addition, examination of SBPS/SLS mixtures in model
      shampoos showed that the presence of the SBPS enables the concentration of SLS to
      be significantly reduced without sacrificing shampoo performance.

PMID- 25066046
TI  - Hamiltonian Monte Carlo methods for efficient parameter estimation in steady
      state dynamical systems.
AB  - BACKGROUND: Parameter estimation for differential equation models of
      intracellular processes is a highly relevant bu challenging task. The available
      experimental data do not usually contain enough information to identify all
      parameters uniquely, resulting in ill-posed estimation problems with often highly
      correlated parameters. Sampling-based Bayesian statistical approaches are
      appropriate for tackling this problem. The samples are typically generated via
      Markov chain Monte Carlo, however such methods are computationally expensive and
      their convergence may be slow, especially if there are strong correlations
      between parameters. Monte Carlo methods based on Euclidean or Riemannian
      Hamiltonian dynamics have been shown to outperform other samplers by making
      proposal moves that take the local sensitivities of the system's states into
      account and accepting these moves with high probability. However, the high
      computational cost involved with calculating the Hamiltonian trajectories
      prevents their widespread use for all but the smallest differential equation
      models. The further development of efficient sampling algorithms is therefore an
      important step towards improving the statistical analysis of predictive models of
      intracellular processes. RESULTS: We show how state of the art Hamiltonian Monte
      Carlo methods may be significantly improved for steady state dynamical models. We
      present a novel approach for efficiently calculating the required geometric
      quantities by tracking steady states across the Hamiltonian trajectories using a
      Newton-Raphson method and employing local sensitivity information. Using our
      approach, we compare both Euclidean and Riemannian versions of Hamiltonian Monte
      Carlo on three models for intracellular processes with real data and demonstrate
      at least an order of magnitude improvement in the effective sampling speed. We
      further demonstrate the wider applicability of our approach to other gradient
      based MCMC methods, such as those based on Langevin diffusions. CONCLUSION: Our
      approach is strictly benefitial in all test cases. The Matlab sources
      implementing our MCMC methodology is available from https://github.com/a
      kramer/ode_rmhmc.

PMID- 25066047
TI  - Risk factors for uterine diseases on small- and medium-sized dairy farms
      determined by clinical, bacteriological, and cytological examinations.
AB  - The involution process of the postpartum bovine uterus is usually accompanied by
      invasion of various bacteria. The objectives of this study were to identify the
      relationship between the postpartum findings as risk factors for clinical
      endometritis (CE) and subclinical endometritis (SE). Furthermore, the effects of
      CE or SE on reproductive performance in small- and medium-sized dairy herds were
      investigated. A total of 400 cows were examined by vaginoscopy for CE at 20 to 30
      days postpartum, and samples were collected for cytological examinations for SE
      and for bacteriology by cytobrush technique. The vaginoscopic and cytological
      examinations showed that 27.3% and 21.0% of the cows were found with CE and SE,
      respectively. The bacterial community analyses revealed a large variety of
      bacteria. Overall, bacteria from the order Actinomycetales, Lactobacillales,
      Bacillales, Burkholderiales, Caulobacteriales Enterobacteriales, Pasteurellales,
      and Pseudomonadales were detected, whereas in 39.5% of the samples no bacterial
      growth was detectable. The uterine pathogens Escherichia coli and Trueperella
      pyogenes were found in 16.8% and 13.0% of the samples cultivated under aerobic
      conditions. Other frequently isolated bacteria were Streptococcus spp. (31.3%),
      Staphylococcus spp. (20.0%), Corynebacterium spp. (16.5%), and Bacillus spp.
      (10.5%). The infection with T. pyogenes was the most important bacteriological
      risk factor for the occurrence of CE (odds ratio (OR) = 5.72; 95% CI = 3.07
      10.83) and had a detrimental effect on the hazard of nonpregnancy by 200 days
      postpartum (hazard ratio = 1.66; 95% CI = 1.12-2.46). Calving assistance (OR =
      1.79; 95% CI = 1.16-2.98) and farm (OR = 1.11; 95% CI = 1.02-1.20) were indicated
      as further risk factors for CE and SE. Effects of CE and SE on reproductive
      performance parameters could not be demonstrated.

PMID- 25066048
TI  - Study of nuclear and acrosomal sperm morphometry in ram using a computer-assisted
      sperm morphometry analysis fluorescence (CASMA-F) method.
AB  - The aim of this study was to develop a new method that allows morphometric
      assessment of the sperm nucleus and acrosome in the ram using fluorescence
      microscopy and free software. The study was divided into three experiments. In
      the first experiment, semen smears from 20 ejaculates were fixed and labeled with
      a propidium iodide-pisum sativum agglutinin (PI/PSA) combination. Digital images
      of the sperm nucleus, acrosome, and whole sperm head were captured and analyzed
      using the ImageJ program. The computer-assisted sperm morphometry analysis
      fluorescence (CASMA-F) method used allowed the differentiation, capture, and
      morphometric analysis of most sperm nuclei, acrosomes, and whole heads with high
      precision and the assessment of the acrosomal status. In the second experiment,
      sperm nuclear morphometry by CASMA-F was compared by staining with the PI/PSA
      combination and staining with Hoechst 33342 as in previous studies. Similar
      results were obtained using both methods. In the third experiment, CASMA-F with
      PI/PSA was compared with a more conventional CASMA method (semen smears stained
      with Hemacolor (HEM) and processed with the ISAS commercial software, HEM).
      Spermatozoa displayed a bigger size when processed with CASMA-F than with HEM
      method in all primary sperm head morphometric parameters, but results using both
      methods were correlated. It was concluded that the CASMA-F method allows the
      simultaneous assessment of sperm nucleus, acrosome, and head in the ram.

PMID- 25066049
TI  - 405 nm light technology for the inactivation of pathogens and its potential role
      for environmental disinfection and infection control.
AB  - BACKGROUND: Although the germicidal properties of ultraviolet (UV) light have
      long been known, it is only comparatively recently that the antimicrobial
      properties of visible violet-blue 405 nm light have been discovered and used for
      environmental disinfection and infection control applications. AIM: To review the
      antimicrobial properties of 405 nm light and to describe its application as an
      environmental decontamination technology with particular reference to
      disinfection of the hospital environment. METHODS: Extensive literature searches
      for relevant scientific papers and reports. FINDINGS: A large body of scientific
      evidence is now available that provides underpinning knowledge of the 405 nm
      light-induced photodynamic inactivation process involved in the destruction of a
      wide range of prokaryotic and eukaryotic microbial species, including resistant
      forms such as bacterial and fungal spores. For practical application, a high
      intensity narrow-spectrum light environmental disinfection system (HINS-light
      EDS) has been developed and tested in hospital isolation rooms. The trial results
      have demonstrated that this 405 nm light system can provide continuous
      disinfection of air and exposed surfaces in occupied areas of the hospital,
      thereby substantially enhancing standard cleaning and infection control
      procedures. CONCLUSION: Violet-blue light, particularly 405 nm light, has
      significant antimicrobial properties against a wide range of bacterial and fungal
      pathogens and, although germicidal efficacy is lower than UV light, this
      limitation is offset by its facility for safe, continuous use in occupied
      environments. Promising results on disinfection efficacy have been obtained in
      hospital trials but the full impact of this technology on reduction of healthcare
      associated infection has yet to be determined.

PMID- 25066050
TI  - Low prevalence of human immunodeficiency virus and hepatitis C virus co-infection
      in a medium size city in southern Brazil.

PMID- 25066051
TI  - At the crossroads between early or delayed antiretroviral therapy initiation
      during tuberculosis/human immunodeficiency virus coinfection.

PMID- 25066052
TI  - Synthesis of protoporphyrin-lipids and biological evaluation of micelles and
      liposomes.
AB  - Protoporphyrin IX (PPIX) lipids were synthesized by introducing a long alkyl
      chain, such as C13, C15, and C17, at each vinyl group on PPIX via
      hydrobromination. The PPIX lipids exhibited a water-soluble property by forming
      their micelles in water and the PPIX-lipid micelles showed relatively low
      cytotoxicity toward HeLa cells (IC50=151.7-379.9MUM) without light irradiation.
      PL-C17 liposomes (post-inserted liposomes) were readily prepared by adding PL-C17
      micelle solution to the liposome solution. The IC50 values of PPIX, PL-C17
      micelles, and PL-C17 liposomes toward HeLa cells were 0.53, 5.65, and 12.9MUM,
      respectively, after irradiation with a xenon lamp in the 400-800nm range for
      2min. PL-C17 liposomes were selectively accumulated in the Golgi apparatus in
      cells. 

PMID- 25066053
TI  - Deep brain stimulation for obsessive-compulsive disorder: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Deep brain stimulation (DBS) is increasingly being applied to
      psychiatric conditions such as obsessive-compulsive disorder (OCD), major
      depression and anorexia nervosa. Double-blind, randomized controlled trials
      (RCTs) of active versus sham treatment have been limited to small numbers. We
      therefore undertook a systematic review and meta-analysis of the effectiveness of
      DBS in psychiatric conditions to maximize study power. METHOD: We conducted a
      systematic literature search for double-blind, RCTs of active versus sham
      treatment using Pubmed/Medline and EMBASE up to April 2013. Where possible, we
      combined results from studies in a meta-analysis. We assessed differences in
      final values between the active and sham treatments for parallel-group studies
      and compared changes from baseline score for cross-over designs. RESULTS:
      Inclusion criteria were met by five studies, all of which were of OCD. Forty-four
      subjects provided data for the meta-analysis. The main outcome was a reduction in
      obsessive symptoms as measured by the Yale-Brown Obsessive Compulsive Scale
      (YBOCS). Patients on active, as opposed to sham, treatment had a significantly
      lower mean score [mean difference (MD) -8.93, 95% confidence interval (CI) -13.35
      to -5.76, p < 0.001], representing partial remission. However, one-third of
      patients experienced significant adverse effects (n = 16). There were no
      differences between the two groups in terms of other outcomes. CONCLUSIONS: DBS
      may show promise for treatment-resistant OCD but there are insufficient
      randomized controlled data for other psychiatric conditions. DBS remains an
      experimental treatment in adults for severe, medically refractory conditions
      until further data are available.

PMID- 25066054
TI  - Reflections on how wound healing-promoting effects of the hair follicle can be
      translated into clinical practice.
AB  - Clinicians have long reported that hair-bearing areas tend to heal more rapidly
      than those lacking hair follicles. In the past decade, numerous scientific
      studies have corroborated clinical evidence, showing a direct nexus between the
      human hair follicle and the wound healing process. The migration of epithelial
      follicular stem cells to the skin surface to help in the wound re
      epithelialization and the effect of the hair cycle on the wound healing rate
      underline the influence of the hair follicle in the healing process. In clinical
      practice, non-healing wounds are pathologies of high prevalence with significant
      associated burden costs for the healthcare system. As the population ages, the
      prevalence of this pathology is expected to increase in future years. The recent
      advances in understanding the biology of hair follicle stem cells have created
      the challenges of using this newly acquired knowledge in practical therapeutic
      applications. Chronic leg ulcers are an example of the targeted pathologies that
      urgently need better therapies. In this essay, our aim is to raise interest in
      this question, reviewing what is known in relation to the connections between
      hair follicles and wound healing, and elaborating on future directions that the
      field might take, including implications for clinical practice. 

PMID- 25066055
TI  - The ER-associated degradation adaptor protein Sel1L regulates LPL secretion and
      lipid metabolism.
AB  - Sel1L is an essential adaptor protein for the E3 ligase Hrd1 in the endoplasmic
      reticulum (ER)-associated degradation (ERAD), a universal quality-control system
      in the cell; but its physiological role remains unclear. Here we show that mice
      with adipocyte-specific Sel1L deficiency are resistant to diet-induced obesity
      and exhibit postprandial hypertriglyceridemia. Further analyses reveal that Sel1L
      is indispensable for the secretion of lipoprotein lipase (LPL), independent of
      its role in Hrd1-mediated ERAD and ER homeostasis. Sel1L physically interacts
      with and stabilizes the LPL maturation complex consisting of LPL and lipase
      maturation factor 1 (LMF1). In the absence of Sel1L, LPL is retained in the ER
      and forms protein aggregates, which are degraded primarily by autophagy. The
      Sel1L-mediated control of LPL secretion is also seen in other LPL-expressing cell
      types including cardiac myocytes and macrophages. Thus, our study reports a role
      of Sel1L in LPL secretion and systemic lipid metabolism.

PMID- 25066058
TI  - Raising the glass ceiling: not all "men" are created equal.

PMID- 25066056
TI  - Mutation of Nogo-B receptor, a subunit of cis-prenyltransferase, causes a
      congenital disorder of glycosylation.
AB  - Dolichol is an obligate carrier of glycans for N-linked protein glycosylation, O
      mannosylation, and GPI anchor biosynthesis. cis-prenyltransferase (cis-PTase) is
      the first enzyme committed to the synthesis of dolichol. However, the proteins
      responsible for mammalian cis-PTase activity have not been delineated. Here we
      show that Nogo-B receptor (NgBR) is a subunit required for dolichol synthesis in
      yeast, mice, and man. Moreover, we describe a family with a congenital disorder
      of glycosylation caused by a loss of function mutation in the conserved C
      terminus of NgBR-R290H and show that fibroblasts isolated from patients exhibit
      reduced dolichol profiles and enhanced accumulation of free cholesterol
      identically to fibroblasts from mice lacking NgBR. Mutation of NgBR-R290H in man
      and orthologs in yeast proves the importance of this evolutionarily conserved
      residue for mammalian cis-PTase activity and function. Thus, these data provide a
      genetic basis for the essential role of NgBR in dolichol synthesis and protein
      glycosylation. 

PMID- 25066057
TI  - Home food environment in relation to children's diet quality and weight status.
AB  - The objective of this cohort study was to explore relationships among the home
      food environment (HFE), child/parent characteristics, diet quality, and measured
      weight status among 699 child-parent pairs from King County, WA, and San Diego
      County, CA. HFE variables included parenting style/feeding practices, food rules,
      frequency of eating out, home food availability, and parents' perceptions of food
      costs. Child dietary intake was measured by 3-day recall and diet quality
      indicators included fruits and vegetables, sweet/savory snacks, high-calorie
      beverages, and Dietary Approaches to Stop Hypertension (DASH) score. Individual
      linear regression models were run in which child BMI z score and child diet
      quality indicators were dependent variables and HFE variables and child/parent
      characteristics were independent variables of interest. Fruit and vegetable
      consumption was associated with parental encouragement/modeling (beta=.68,
      P<0.001) and unhealthful food availability (-0.27, P<0.05); DASH score with food
      availability (healthful: 1.3, P<0.01; unhealthful: -2.25, P<0.001), food rules
      (0.45, P<0.01), and permissive feeding style (-1.04, P<0.05); high-calorie
      beverages with permissive feeding style (0.14, P<0.01) and unhealthful food
      availability (0.21, P<0.001); and sweet/savory snacks with healthful food
      availability (0.26, P<0.05; unexpectedly positive). Children's BMI z score was
      positively associated with parent's use of food restriction (0.21, P<0.001),
      permissive feeding style (0.16, P<0.05), and concern for healthy food costs
      (0.10, P<0.01), but negatively with verbal encouragement/modeling (-0.17,
      P<0.05), and pressure to eat (-0.34, P<0.001). Various HFE factors associated
      with parenting around eating and food availability are related to child diet
      quality and weight status. These factors should be considered when designing
      interventions for improving child health. 

PMID- 25066059
TI  - Vestibular anesthesia test for neuroproliferative vestibulodynia.

PMID- 25066061
TI  - Efficient organic sensitizers with pyridine-N-oxide as an anchor group for dye
      sensitized solar cells.
AB  - Five organic dyes with pyridine-N-oxide as the anchor group and electron acceptor
      have been synthesized and applied in dye-sensitized solar cells (DSSCs).
      Benzothiadiazole was introduced in the conjugation system to increase the
      electron withdrawing properties, FTIR spectra showed that the coordination was
      between the pyridine-N-oxide and the Bronsted acid site on the TiO2 surface. The
      relationship between different dye structures and the performance of the DSSCs
      was investigated systematically. The location of the thiophene unit was studied,
      and the direct linkage of benzothiadiazole with pyridine-N-oxide was beneficial
      to broaden the absorption. The donor-acceptor-acceptor-configured dye WL307,
      which has 2-ethylhexyloxy chains in the donor part, showed the best efficiency of
      6.08% under 100 mW cm(-2) light illumination. The dye series showed a fairly good
      stability during the one month test period.

PMID- 25066062
TI  - Partitioning the etiology of hoarding and obsessive-compulsive symptoms.
AB  - BACKGROUND: Until recently, hoarding was considered an obsessive-compulsive
      symptom (OCS). However, current evidence suggests that these two phenotypes may
      be clinically, and perhaps etiologically, distinct. Both hoarding and OCS have a
      genetic etiology, but the degree of unique and shared genetic contributions to
      these phenotypes has not been well studied. METHOD: Prevalence rates were
      assessed for hoarding and OCS in a sample of adult twin pairs (n = 7906 twins)
      and their family members from The Netherlands Twin Register (total sample =
      15,914). Using Mplus, genetic analyses using liability threshold models were
      conducted for both phenotypes, for their co-morbidity, and for specific hoarding
      symptoms (cluttering, discarding and acquiring). RESULTS: Of the total sample,
      6.7% met criteria for clinically significant hoarding; endorsement of all three
      hoarding symptoms was > or = 79%. Men had slightly higher rates than women. Also,
      5.7% met criteria for clinically significant OCS; rates were similar in males and
      females. Genetic factors accounted for 36% of the variance for hoarding and 40%
      of the variance for OCS. The genetic correlation between hoarding and OCS was
      0.10. There was no evidence of sex-specific genetic contributions for hoarding or
      OCS. There was evidence for a genetic contribution to all hoarding symptom
      subtypes. Only cluttering showed evidence of a contribution from the shared
      environment. CONCLUSIONS: OCS and hoarding are common in this population-based
      sample, have prevalence rates similar to those previously reported, and show
      significant heritability. Genetic factors contributed to the co-morbidity of both
      traits, although the genetic correlation between them was low.

PMID- 25066063
TI  - Correlates of leptin in children with chronic kidney disease.
AB  - OBJECTIVE: To investigate the relative associations of renal function, obesity,
      and inflammation with serum leptin levels in children with chronic kidney disease
      (CKD). STUDY DESIGN: This was a cross-sectional analysis of 317 children from the
      Chronic Kidney Disease in Children study, a large cohort of pediatric patients
      with stage II-IV CKD. Linear regression modeling was used to evaluate the
      association of serum leptin level with glomerular filtration rate calculated
      using the plasma iohexol disappearance curve, demographics, body mass index
      (BMI), and cardiovascular risk factors, including inflammatory cytokines, insulin
      resistance, and serum lipid levels. RESULTS: In univariate analyses, elevated
      serum leptin level was significantly associated with increased BMI, older age,
      and female sex (P < .001 for all). Leptin level also correlated positively with
      serum triglycerides and insulin resistance (P < .001) and negatively with serum
      high-density lipoprotein cholesterol (P = .002). Leptin level was not associated
      with glomerular filtration rate calculated using the plasma iohexol disappearance
      curve or inflammatory cytokines. In multivariate analysis, BMI, age, female sex,
      and serum triglyceride levels were significantly associated with serum leptin
      level. CONCLUSION: Increased leptin production was associated with female sex,
      older age, and adiposity in children with mild to moderate CKD. Renal function
      was not associated with serum leptin level, indicating that decreased clearance
      does not contribute to elevated leptin levels.

PMID- 25066064
TI  - Sleep duration and obesity among adolescents transitioning to adulthood: do
      results differ by sex?
AB  - OBJECTIVES: To examine the association between short sleep duration and obesity
      among adolescents (mean age 16 years) transitioning into young adulthood (mean
      age 21 years) in the National Longitudinal Study of Adolescent Health (N =
      10,076). STUDY DESIGN: Self-reported sleep duration was categorized as <6, 6-8,
      or >8 hours. Obesity status, using measured height and weight, was defined as
      body mass index >=95th percentile in adolescence and body mass index >=30 kg/m(2)
      in young adulthood. RESULTS: Cross-sectionally, short sleep duration was
      associated with obesity in adolescent males (prevalence ratio 1.8 [95% CI, 1.3
      2.4]) but not in females (prevalence ratio 1.0 [95% CI, 0.7-1.4]). In
      longitudinal analyses, short sleep duration in adolescence was associated with
      incident obesity in both males and females (risk ratio 1.2 [95% CI, 1.0-1.6]) in
      young adulthood. No interactions by sex were noted. CONCLUSIONS: Analyzing the
      association of sleep duration and obesity longitudinally resolved sex
      discrepancies observed in earlier cross-sectional analyses. Optimizing sleep
      duration during adolescence may be an effective intervention to prevent excess
      weight gain in young adults.

PMID- 25066065
TI  - Cri du chat syndrome and primary ciliary dyskinesia: a common genetic cause on
      chromosome 5p.
AB  - Cri du chat syndrome (CdCS) and primary ciliary dyskinesia (PCD) are rare
      diseases that present with frequent respiratory symptoms. PCD can be caused by
      hemizygous DNAH5 mutation in combination with a 5p segmental deletion
      attributable to CdCS on the opposite chromosome. Chronic oto-sino-pulmonary
      symptoms or organ laterality defects in CdCS should prompt an evaluation for PCD.

PMID- 25066066
TI  - Crystal structure of a feruloyl esterase belonging to the tannase family: a
      disulfide bond near a catalytic triad.
AB  - Feruloyl esterase (FAE) catalyzes the hydrolysis of the ferulic and diferulic
      acids present in plant cell wall polysaccharides, and tannase catalyzes the
      hydrolysis of tannins to release gallic acid. The fungal tannase family in the
      ESTHER database contains various enzymes, including FAEs and tannases. Despite
      the importance of FAEs and tannases in bioindustrial applications, three
      dimensional structures of the fungal tannase family members have been unknown.
      Here, we determined the crystal structure of FAE B from Aspergillus oryzae
      (AoFaeB), which belongs to the fungal tannase family, at 1.5 A resolution. AoFaeB
      consists of a catalytic alpha/beta-hydrolase fold domain and a large lid domain,
      and the latter has a novel fold. To estimate probable binding models of
      substrates in AoFaeB, an automated docking analysis was performed. In the active
      site pocket of AoFaeB, residues responsible for the substrate specificity of the
      FAE activity were identified. The catalytic triad of AoFaeB comprises Ser203,
      Asp417, and His457, and the serine and histidine residues are directly connected
      by a disulfide bond of the neighboring cysteine residues, Cys202 and Cys458. This
      structural feature, the "CS-D-HC motif," is unprecedented in serine hydrolases. A
      mutational analysis indicated that the novel structural motif plays essential
      roles in the function of the active site.

PMID- 25066067
TI  - Health information technology workforce needs of rural primary care practices.
AB  - PURPOSE: This study assessed electronic health record (EHR) and health
      information technology (HIT) workforce resources needed by rural primary care
      practices, and their workforce-related barriers to implementing and using EHRs
      and HIT. METHODS: Rural primary care practices (1,772) in 13 states (34.2%
      response) were surveyed in 2012 using mailed and Web-based questionnaires.
      FINDINGS: EHRs or HIT were used by 70% of respondents. Among practices using or
      intending to use the technology, most did not plan to hire new employees to
      obtain EHR/HIT skills and even fewer planned to hire consultants or vendors to
      fill gaps. Many practices had staff with some basic/entry, intermediate and/or
      advanced-level skills, but nearly two-thirds (61.4%) needed more staff training.
      Affordable access to vendors/consultants who understand their needs and
      availability of community college and baccalaureate-level training were the
      workforce-related barriers cited by the highest percentages of respondents.
      Accessing the Web/Internet challenged nearly a quarter of practices in isolated
      rural areas, and nearly a fifth in small rural areas. Finding relevant
      vendors/consultants and qualified staff were greater barriers in small and
      isolated rural areas than in large rural areas. DISCUSSION/CONCLUSIONS: Rural
      primary care practices mainly will rely on existing staff for continued
      implementation and use of EHR/HIT systems. Infrastructure and workforce-related
      barriers remain and must be overcome before practices can fully manage patient
      populations and exchange patient information among care system partners. Efforts
      to monitor adoption of these skills and ongoing support for continuing education
      will likely benefit rural populations.

PMID- 25066068
TI  - Situating universal design architecture: designing with whom?
AB  - PURPOSE: To respond to growing calls for a theoretical unpacking of Universal
      Design (UD), a disparate movement cohering around attempts to design spaces and
      technologies that seek to allow use by all people (to the fullest extent
      possible). The on-going embedding of UD into architectural practice and pedagogy
      represents an opportune juncture at which to draw learning from other distinct
      but-related transformatory architectural movements. METHODS: Sociological
      theoretical commentary. RESULTS: UD has to date, and necessarily, been dominated
      by the practice contexts from which it emerged. Appealing as a short-hand for
      description of "designing-for-all", in most cases UD has come to stand in as a
      term to signal a general intent in this direction and as an umbrella term for the
      range of technical design resources that have been developed under these
      auspices. There remains a fundamental ambivalence vis-a-vis the question of
      users' power/capacity to influence decision-making in the design process in UD;
      technically-oriented typologies of bodies predominate in influential UD
      architectural accounts. CONCLUSIONS: UD represents rich technical and pedagogical
      resources for those architects committed to transforming the existing built
      environment so as to be less hostile to a wide range of users. However, within
      UD, unpacking the social role of the professional architect vis-a-vis a variety
      of publics is an important, but hitherto underdeveloped, challenge; issues
      concerning professional-citizen power relations continue to animate parallel
      architectural politics, and UD can both contribute and draw much from these on
      going explorations. Implications for Rehabilitation Universal Design (UD)
      architecture shares a close affinity with rehabilitation practice, with the
      creation of built environments that allow use by individuals with a wide range of
      capacities a priority for both. While an effective communicative "bridge" between
      professions, UD's deployment typically leaves unspoken the capacity of users to
      meaningfully affect decision-making in the design process. UD architecture has
      much to draw from, and contribute to, parallel movements in "participatory
      architectural design"; debates therein have illuminated much about the social
      practices underpinning designing for difference. UD could engage more fully with
      questions relating to the social and political role of the architect.

PMID- 25066069
TI  - A scoping review of rehabilitation interventions that reduce fatigue among adults
      with multiple sclerosis.
AB  - OBJECTIVE: To identify and summarize available research literature about
      rehabilitation interventions for multiple sclerosis (MS) fatigue management.
      METHODS: Database searches (PubMed, EMBASE, CINAHL and PsychINFO) were conducted
      in October 2011 and last updated in July 2013. To be included, studies must have
      been published in a peer-reviewed scientific journal, written in English and
      included an intervention to manage MS fatigue. Effect size (ES) were calculated
      for the quantitative studies to estimate intervention effects, and major themes
      were summarized for the qualitative studies. RESULTS: Thirty-eight studies were
      included in this review. A variety of exercise and behavior change interventions
      were prescribed to adults with MS. The two most common interventions were
      progressive resistive training and fatigue management programs. Three exercise
      intervention studies and nine behavior change intervention studies with
      quantitative data presented significant ES. Four studies with qualitative data
      supported the positive impact of certain exercise and behavior change
      interventions. CONCLUSIONS: This review identified a variety of exercise and
      behavior change interventions for MS fatigue management. While the findings may
      provide helpful information to inform practice, future researchers need to
      develop and evaluate knowledge translation strategies to facilitate the
      application of this evidence to daily practice to advance MS rehabilitation care.
      IMPLICATIONS FOR REHABILITATION: Both exercise and behavior change interventions
      demonstrate some degree of effectiveness for managing MS fatigue. Effect sizes
      for exercise and behavior change interventions are similar, although the
      populations examined are different. Overall, evidence for exercise focuses on
      people who are less disabled, while evidence for behavior change interventions
      includes a broader population. Future researchers need to develop and evaluate
      knowledge translation strategies that facilitate application of evidence in daily
      practice in order to advance MS rehabilitation.

PMID- 25066070
TI  - Muscle size and strength in children with cerebral palsy.

PMID- 25066071
TI  - A meta-analysis of the prevalence of attention deficit hyperactivity disorder in
      incarcerated populations.
AB  - BACKGROUND: Studies report the variable prevalence of attention deficit
      hyperactivity disorder (ADHD) in incarcerated populations. The aim of this meta
      analysis was to determine the prevalence of ADHD in these populations. METHOD:
      Primary research studies reporting the prevalence (lifetime/current) of ADHD in
      incarcerated populations were identified. The meta-analysis used a mixed log
      binomial model, including fixed effects for each covariate and a random study
      effect, to estimate the significance of various risk factors. RESULTS: Forty-two
      studies were included in the analysis. ADHD prevalence was higher with screening
      diagnoses versus diagnostic interview (and with retrospective youth diagnoses
      versus current diagnoses). Using diagnostic interview data, the estimated
      prevalence was 25.5% and there were no significant differences for gender and
      age. Significant country differences were noted. CONCLUSIONS: Compared with
      published general population prevalence, there is a fivefold increase in
      prevalence of ADHD in youth prison populations (30.1%) and a 10-fold increase in
      adult prison populations (26.2%).

PMID- 25066072
TI  - Hypoglycemic effect of Gynostemma pentaphyllum saponins by enhancing the Nrf2
      signaling pathway in STZ-inducing diabetic rats.
AB  - Gynostemma pentaphyllum (GP) is a natural plant resources for diabetes therapy,
      however, there is little research on the mechanisms of GP. The present study was
      undertaken to characterize if G. pentaphyllum saponins (GPs) is the principal
      active compound of GP responsible for anti-diabetes, and to examine the
      relativity between blood glucose modulate and antioxidation. The GPs-treated
      streptozotocin diabetic rats had a more effective hypoglycemic status than those
      of diabetic control rats, which also ameliorate dyslipidemia. GPs has increased
      SOD and GSH-px activities, and the spleen and thymus indexes in diabetic rats.
      The insulin levels in the GPs-treated groups were significantly higher than
      diabetic control group. Our finding provides a new insight into the application
      of GPs for the treatment of oxidative stress related diseases. 

PMID- 25066073
TI  - Antimelanogenic chemicals with in vivo efficacy against skin pigmentation in
      guinea pigs.
AB  - Ultraviolet (UV) radiation under sunlight stimulates skin pigmentation through
      immediately affecting the oxidative modification of existing melanin pigments and
      the spatial redistribution of pigmented melanosomes followed by the up-regulation
      of melanogenic genes in delayed kinetics. However, abnormal accumulation and
      synthesis of melanin biopolymers are responsible for skin disorders with more
      pigmented patches. Chemical-based regulation of the hyperpigmented disorders has
      been a long-standing goal for cosmetic and pharmaceutical applications. A large
      number of the chemicals with antimelanogenic activity have met with limited or no
      success in the treatment of skin patients, since they may not overcome the
      challenge of penetrating the skin barrier. Guinea pig skin displays similar
      kinetic parameters to human skin in the transdermal absorption of numerous
      chemicals, thus can serve as the surrogate for human skin. Here, we provide a
      concise review of our current understanding of the chemical-based therapy against
      skin hyperpigmentation in UV-irradiated guinea pig models, suggest molecular
      mechanisms of the action and emphasize the translation from preclinical outcomes
      to skin patients. 

PMID- 25066074
TI  - Electrospinning of diosmin from aqueous solutions for improved dissolution and
      oral absorption.
AB  - A nanofibrous membrane carrier for nearly water insoluble drug diosmin was
      formulated. The aim of this study was to evaluate the drug release and
      dissolution properties in an aqueous buffer of pH 7.8, and to compare the
      suitability of the drug carrier with the available drug forms and screen diosmin
      absorption extent. The membranes were produced from HPC/PVA/PEO-drug water
      solutions and then evaluated by SEM and DSC measurements. The results showed that
      diosmin was incorporated within the nanofibers in an amorphous state, and/or as a
      solid dispersion. The results of in vitro release experiments excerpt a very fast
      release of the drug, followed by the formation of an over saturated solution and
      partial precipitation of the drug (a "spring" effect). The enormous increases in
      dissolution of the drug from a nanofibrous carrier, compared to a micronized and
      crystalline form, was achieved. The in vivo bioavailability study carried out on
      rats showed higher initial drug plasma levels and higher AUC values after
      administration of the nanofibrous drug formulation, compared to the micronized
      form. The results of the study demonstrated that the improvement of the diosmin
      in vitro dissolution also brought the enhanced in vivo absorption extent of the
      drug. 

PMID- 25066075
TI  - New celecoxib multiparticulate systems to improve glioblastoma treatment.
AB  - Treatment of malignant gliomas consists of resection followed by radiotherapy and
      chemotherapy. Celecoxib (CXB), a selective COX-2 inhibitor, is able to control
      inflammation and pain, to improve the efficacy of radiotherapy, and to inhibit at
      high doses the growth of cancer cells. Two new delivery systems for CXB are
      developed: microspheres (MPs) for implantation in the brain after
      partial/complete removal of the tumor, and nanoparticles (NPs) for their
      potential to cross the blood brain barrier and deliver CXB into the CNS. Cell
      culture assays performed in PC12, SKN-AS and U373-MG cells demonstrate the
      antiproliferative affects of CXB, with EC50 values of 99.81 MUM and 82.4 MUM in
      U373-MG and SKN-AS cells. Encapsulation efficacy of CXB in formulation MP2 (20%
      CXB) was 74.6 +/- 2.2% with a zero-order release rate of 47.8 MUg/day/20mg
      microspheres for 34 days. Uncoated and polysorbate 80-coated CXB-NPs are prepared
      by nanoprecipitation. Mean sizes of uncoated and coated CXB-NPs were 173.6 +/-
      44.9 nm and 100.6 +/- 62.1 nm. Cerebral cortex images showed a marked increase of
      fluorescence when the surfactant-coated NPs were administered to rats. These
      results suggest that both CXB formulations (MPs and NPs) are adequate systems to
      enhance the effects of chemotherapy in the treatment of malignant brain tumor.

PMID- 25066076
TI  - Cytarabine-AOT catanionic vesicle-loaded biodegradable thermosensitive hydrogel
      as an efficient cytarabine delivery system.
AB  - Carrier with high drug loading content is one of the most important issues in
      drug delivery system. In the present work, an ion-pair amphiphilic molecule
      composed of anticancer drug cation and surfactant anion is used for
      straightforward fabricating vesicles for cancer therapy. Anticancer drug
      (cytarabine hydrochloride) and anionic surfactant (AOT) are selected for the
      fabrication of ion-pair amphiphilic molecule. One amphiphilic molecule contains
      one drug cation, thus the drug loading content is 50% (mol/mol) in theory. The in
      vitro drug release study shows that the release time of cytarabine is about 3
      times of the pure cytarabine solution and the permeability of cytarabine has been
      improved about 160 times tested by parallel artificial membrane permeability
      assay model. However, the hemolytic toxicity is largely decreased in the studied
      concentration range. The in vitro cytotoxicity results show that cytarabine-AOT
      amphiphiles have a much lower IC50 (drug concentration resulting in 50% cell
      death) value and a higher cell inhibition rate comparing with their respective
      components, indicating its effective therapy for leukemic cells. To obtain a
      longer and a convenient drug release system, the prepared vesicles are further
      incorporated into the thermosensitive PLGA-PEG-PLGA hydrogel to prepare a
      subcutaneous administration. The in vivo drug release results indicate that
      cytarabine-AOT vesicle-loaded hydrogel is a good injectable delivery system for
      controlled release of cytarabine for cancer therapy.

PMID- 25066077
TI  - Bixin loaded solid lipid nanoparticles for enhanced hepatoprotection-
      preparation, characterisation and in vivo evaluation.
AB  - In the present study, a natural antioxidant drug, bixin was loaded into solid
      lipid nanoparticles using trimyristin and glycerol monostearate as different
      lipid matrices and soya and egg lecithin as stabilizers. Developed bixin SLNs
      were characterized including in vitro drug release and in vivo evaluation of
      hepatoprotective activity using Wistar rats. Bixin SLNs were prepared by hot
      homogenisation followed by ultrasonication technique. The particle size ranged
      from 135.5-352.8 nm with PDI 0.185-0.572. Zeta potential of bixin SLNs was -17.9
      to -36.5 mV. Bixin was successfully incorporated into SLNs with entrapment
      efficiency above 99% and loading efficiency maximum 17.96%. There was no
      interaction of bixin with selected lipids TM and GMS, confirmed by FTIR studies.
      DSC studies revealed that preparation method did not change crystallinity of
      bixin and TM whereas GMS crystallinity was reduced. In vitro drug release studies
      in Sorensen buffer, pH 7.7 exhibited initial burst effect followed by a sustained
      release of bixin. Drug release kinetic studies showed that the release was first
      order diffusion controlled and the n-values obtained from the Korsmeyer-Peppas
      model indicated the release mechanism was non-Fickian type. In vivo studies
      revealed better treatment of paracetamol induced hepatotoxicity by bixin SLNs
      indicating significant localisation of them in liver.

PMID- 25066078
TI  - 1H NMR profiling as an approach to differentiate conventionally and organically
      grown tomatoes.
AB  - This study describes the approach of (1)H NMR profiling for the authentication of
      organically produced tomatoes (Solanum lycopersicum). Overall, 361 tomato samples
      of two different cultivars and four different producers were regularly analyzed
      during a 7 month period. The results of principal component analysis showed a
      significant trend for the separation between organically and conventionally
      produced tomatoes (p < 0.001 using the t test). Linear discriminant analysis
      demonstrated good discrimination between the growing regimens, and external
      validation showed 100% correctly classified tomato samples. Further validation
      studies, however, also disclosed unexpected differences between individual
      producers, which interfere with the aim of predicting the cultivation method, yet
      the results indicate significant differences between (1)H NMR spectra of
      organically and conventionally grown tomatoes. 

PMID- 25066079
TI  - Are we seeing the full picture of peer-assessment in medical education?

PMID- 25066080
TI  - Shooting in a foam.
AB  - We study the motion of a solid sphere after its fast impact on a bath of liquid
      foam. We identify two regimes of deceleration. At short times, the velocity is
      still large and the foam behaves similar to a Newtonian fluid of constant
      viscosity. Then we measure a velocity threshold below which the sphere starts
      experiencing the foam's elasticity. We interpret this behavior using a visco
      elasto-plastic model for foam rheology. Finally we discuss the possibility of
      stopping a projectile in the foam, and evaluate the capture efficiency. 

PMID- 25066081
TI  - In vitro effects of household products on Calliphoridae larvae development:
      implication for forensic entomology.
AB  - Several parameters can delay the first arrival of flies on a corpse and the
      subsequent development of the larvae. This study focuses on the development of
      Lucilia sericata (Diptera: Calliphoridae) (Meigen, 1826) on household chemical
      contaminated substrates. bleach, perfume, hydrochloric acid, caustic soda,
      insecticide, mosquito repellent, and gasoline in quantities consistent with an
      amount that could possibly be spilled on a corpse were mixed with beef liver to
      simulate contaminated fleshes. Larvae were bred at 25  degrees C on these media
      until emergence. Four developmental parameters were followed: survival rates,
      development times, sex ratios, and adult sizes. Hydrochloric acid, insecticide,
      and gasoline killed all larvae. In low quantities, caustic soda and mosquito
      repellent increased the development time and decreased the adult size. However,
      high quantities of these chemicals killed all larvae. Lastly, bleach and perfume
      did not affect the survival rate and barely impacted the development time or
      adult size. These results demonstrate common household products spilled on a
      corpse can strongly affect the development of Calliphoridae larvae. The effects
      of such products should be considered in forensic entomology cases.

PMID- 25066082
TI  - Descending control of swim posture by a midbrain nucleus in zebrafish.
AB  - The reticular formation in the brainstem controls motor output via axonal
      projections to the hindbrain and spinal cord. It remains unclear how individual
      groups of brainstem neurons contribute to specific motor functions. Here, we
      investigate the behavioral role of the nucleus of the medial longitudinal
      fasciculus (nMLF), a small group of reticulospinal neurons in the zebrafish
      midbrain. Calcium imaging revealed that nMLF activity is correlated with bouts of
      swimming. Optogenetic stimulation of neurons in the left or right nMLF activates
      the posterior hypaxial muscle and produces a graded ipsilateral tail deflection.
      Unilateral ablation of a subset of nMLF cells biases the tail position to the
      intact side during visually evoked swims, while sparing other locomotor
      maneuvers. We conclude that activity in the nMLF provides postural control of
      tail orientation and thus steers the direction of swimming. Our studies provide
      an example of fine-grained modularity of descending motor control in vertebrates.

PMID- 25066083
TI  - A reinforcement learning mechanism responsible for the valuation of free choice.
AB  - Humans exhibit a preference for options they have freely chosen over equally
      valued options they have not; however, the neural mechanism that drives this bias
      and its functional significance have yet to be identified. Here, we propose a
      model in which choice biases arise due to amplified positive reward prediction
      errors associated with free choice. Using a novel variant of a probabilistic
      learning task, we show that choice biases are selective to options that are
      predominantly associated with positive outcomes. A polymorphism in DARPP-32, a
      gene linked to dopaminergic striatal plasticity and individual differences in
      reinforcement learning, was found to predict the effect of choice as a function
      of value. We propose that these choice biases are the behavioral byproduct of a
      credit assignment mechanism responsible for ensuring the effective delivery of
      dopaminergic reinforcement learning signals broadcast to the striatum. 

PMID- 25066084
TI  - Neural control and modulation of swimming speed in the larval zebrafish.
AB  - Vertebrate locomotion at different speeds is driven by descending excitatory
      connections to central pattern generators in the spinal cord. To investigate how
      these inputs determine locomotor kinematics, we used whole-field visual motion to
      drive zebrafish to swim at different speeds. Larvae match the stimulus speed by
      utilizing more locomotor events, or modifying kinematic parameters such as the
      duration and speed of swimming bouts, the tail-beat frequency, and the choice of
      gait. We used laser ablations, electrical stimulation, and activity recordings in
      descending neurons of the nucleus of the medial longitudinal fasciculus (nMLF) to
      dissect their contribution to controlling forward movement. We found that the
      activity of single identified neurons within the nMLF is correlated with
      locomotor kinematics, and modulates both the duration and oscillation frequency
      of tail movements. By identifying the contribution of individual supraspinal
      circuit elements to locomotion kinematics, we build a better understanding of how
      the brain controls movement. 

PMID- 25066086
TI  - Coexpressed auxiliary subunits exhibit distinct modulatory profiles on AMPA
      receptor function.
AB  - Gating properties and surface trafficking of AMPA receptors (AMPARs) are
      modulated by auxiliary subunits. Here we studied the function of coexpressed
      auxiliary subunits belonging to two different classes. We focused on TARP gamma-8
      and CKAMP44 in dentate gyrus (DG) granule cells, since both subunits are highly
      expressed in this cell type. TARP gamma-8 and CKAMP44 decrease the rate of
      deactivation but have an opposing influence on receptor desensitization, which
      accounts for their differential modulation of synaptic short-term plasticity.
      Furthermore, long-term plasticity (LTP) requires TARP gamma-8 but not CKAMP44.
      The coexpression of both auxiliary subunits is necessary for the efficient
      targeting of AMPARs to the cell surface of DG granule cells. Finally,
      electrophysiological and biochemical evidence support the notion that CKAMP44 and
      TARP gamma-8 can be contained in the same AMPAR complex.

PMID- 25066085
TI  - Endostatin is a trans-synaptic signal for homeostatic synaptic plasticity.
AB  - At synapses in organisms ranging from fly to human, a decrease in postsynaptic
      neurotransmitter receptor function elicits a homeostatic increase in presynaptic
      release that restores baseline synaptic efficacy. This process, termed
      presynaptic homeostasis, requires a retrograde, trans-synaptic signal of unknown
      identity. In a forward genetic screen for homeostatic plasticity genes, we
      identified multiplexin. Multiplexin is the Drosophila homolog of Collagen
      XV/XVIII, a matrix protein that can be proteolytically cleaved to release
      Endostatin, an antiangiogenesis signaling factor. Here we demonstrate that
      Multiplexin is required for normal calcium channel abundance, presynaptic calcium
      influx, and neurotransmitter release. Remarkably, Endostatin has a specific
      activity, independent of baseline synapse development, that is required for the
      homeostatic modulation of presynaptic calcium influx and neurotransmitter
      release. Our data support a model in which proteolytic release of Endostatin
      signals trans-synaptically, acting in concert with the presynaptic CaV2.1 calcium
      channel, to promote presynaptic homeostasis. 

PMID- 25066087
TI  - Selective responses to tonic descending commands by temporal summation in a
      spinal motor pool.
AB  - Motor responses of varying intensities rely on descending commands to
      heterogeneous pools of motoneurons. In vertebrates, numerous sources of
      descending excitatory input provide systematically more drive to progressively
      less excitable spinal motoneurons. While this presumably facilitates simultaneous
      activation of motor pools, it is unclear how selective patterns of recruitment
      could emerge from inputs weighted this way. Here, using in vivo
      electrophysiological and imaging approaches in larval zebrafish, we find that,
      despite weighted excitation, more excitable motoneurons are preferentially
      activated by a midbrain reticulospinal nucleus by virtue of longer membrane time
      constants that facilitate temporal summation of tonic drive. We confirm the
      utility of this phenomenon by assessing the activity of the midbrain and
      motoneuron populations during a light-driven behavior. Our findings demonstrate
      that weighted descending commands can generate selective motor responses by
      exploiting systematic differences in the biophysical properties of target
      motoneurons and their relative sensitivity to tonic input.

PMID- 25066089
TI  - Mast cell activation: a complex interplay of positive and negative signaling
      pathways.
AB  - Mast cells regulate the immunological responses causing allergy and autoimmunity,
      and contribute to the tumor microenvironment through generation and secretion of
      a broad array of preformed, granule-stored and de novo synthesized bioactive
      compounds. The release and production of mast cell mediators is the result of a
      coordinated signaling machinery, followed by the FcepsilonRI and FcgammaR antigen
      ligation. In this review, we present the latest understanding of FcepsilonRI and
      FcgammaR signaling, required for the canonical mast cell activation during
      allergic responses and anaphylaxis. We then describe the cooperation between the
      signaling of FcR and other recently characterized membrane-bound receptors (i.e.,
      IL-33R and thymic stromal lymphopoietin receptor) and their role in the chronic
      settings, where mast cell activation is crucial for the development and the
      sustainment of chronic diseases, such as asthma or airway inflammation. Finally,
      we report how the FcR activation could be used as a therapeutic approach to treat
      allergic and atopic diseases by mast cell inactivation. Understanding the
      magnitude and the complexity of mast cell signaling is necessary to identify the
      mechanisms underlying the potential effector and regulatory roles of mast cells
      in the biology and pathology of those disease settings in which mast cells are
      activated. 

PMID- 25066090
TI  - Non-medical determinants of cesarean section in a medically dominated maternity
      system.
AB  - OBJECTIVE: To assess the contribution of non-medical factors to actual mode of
      delivery in a setting with high cesarean rates. DESIGN: Follow-up survey.
      SETTING: University department of obstetrics and gynecology. SAMPLE: Women with
      singleton pregnancies (n = 453) where there was no awareness of medical
      contradictions to vaginal delivery, attending for routine mid-pregnancy
      ultrasound examination in November 2011 to March 2012, and delivering between
      March and August 2012. METHODS: Structured questionnaire completed in gestational
      weeks 18-22. Information on subsequent delivery was obtained from patient files
      and through personal contact. MAIN OUTCOME MEASURES: Contribution of childbirth
      preference, Wijma Delivery Expectancy/Experience Questionnaire A score, socio
      demographic characteristics, attitudes toward birth issues and circumstances of
      pregnancy/delivery to mode of delivery. RESULTS: The majority of respondents
      (410/453; 90.5%) preferred vaginal delivery; nevertheless, one-third (two-fifths
      of nulliparas) had a cesarean delivery. Among nulliparous respondents, a longer
      perceived interval from decision for pregnancy to conception, lower importance
      assigned to personal control, and the presence of an obstetrician with power to
      decide about cesarean delivery, were independent contributors to the binary
      logistic regression model explaining higher maternal cesarean risks. For parous
      respondents, corresponding factors were younger maternal age, perceived
      environmental influence towards cesarean section, the respondent's belief that
      cesarean is more beneficial than vaginal delivery and an older obstetrician
      attending the delivery. CONCLUSIONS: The results of this questionnaire survey
      contribute to the already existing evidence that against the background of high
      cesarean rates, non-medical factors, as much related to the obstetricians as to
      pregnant women's attitudes, play an important role.

PMID- 25066088
TI  - Error-monitoring in response to social stimuli in individuals with higher
      functioning Autism Spectrum Disorder.
AB  - Error-monitoring, or the ability to recognize one's mistakes and implement
      behavioral changes to prevent further mistakes, may be impaired in individuals
      with Autism Spectrum Disorder (ASD). Children and adolescents (ages 9-19) with
      ASD (n = 42) and typical development (n = 42) completed two face processing tasks
      that required discrimination of either the gender or affect of standardized face
      stimuli. Post-error slowing and the difference in Error-Related Negativity
      amplitude between correct and incorrect responses (ERNdiff ) were used to index
      error-monitoring ability. Overall, ERNdiff increased with age. On the Gender
      Task, individuals with ASD had a smaller ERNdiff than individuals with typical
      development; however, on the Affect Task, there were no significant diagnostic
      group differences on ERNdiff . Individuals with ASD may have ERN amplitudes
      similar to those observed in individuals with typical development in more social
      contexts compared to less social contexts due to greater consequences for errors,
      more effortful processing, and/or reduced processing efficiency in these
      contexts. Across all participants, more post-error slowing on the Affect Task was
      associated with better social cognitive skills. 

PMID- 25066091
TI  - Associations of regional GABA and glutamate with intrinsic and extrinsic neural
      activity in humans-a review of multimodal imaging studies.
AB  - The integration of multiple imaging modalities is becoming an increasingly well
      used research strategy for studying the human brain. The neurotransmitters
      glutamate and GABA particularly lend themselves towards such studies. This is
      because these transmitters are ubiquitous throughout the cortex, where they are
      the key constituents of the inhibition/excitation balance, and because they can
      be easily measured in vivo through magnetic resonance spectroscopy, as well as
      with select positron emission tomography approaches. How these transmitters
      underly functional responses measured with techniques such as fMRI and EEG
      remains unclear though, and was the target of this review. Consistently shown in
      the literature was a negative correlation between GABA concentrations and
      stimulus-induced activity within the measured region. Also consistently found was
      a positive correlation between glutamate concentrations and inter-regional
      activity relationships, both during tasks and rest. These findings are outlined
      along with results from populations with mental disorders to give an overview of
      what brain imaging has suggested to date about the biochemical underpinnings of
      functional activity in health and disease. We conclude that the combination of
      functional and biochemical imaging in humans is an increasingly informative
      approach that does however require a number of key methodological and
      interpretive issues be addressed before can meet its potential. 

PMID- 25066093
TI  - Stereoselective construction of 1,3-disilylcyclopentane derivatives by scandium
      catalyzed [3+2] cycloaddition of allylsilanes to beta-silylenones.
AB  - The Sc(OTf)3-catalyzed [3+2] cycloaddition of allylsilanes to beta-silyl
      alpha,beta-unsaturated ketones (beta-silylenones) has been developed to form five
      membered syn-1,3-disilylketones diastereoselectively through the rearrangement of
      the silicon substituents on the allylsilane. Stabilization of the carbocation
      intermediates by a double silicon effect plays a key role in directing the course
      of the reaction to favor the [3+2] cycloaddition pathway over simple allylation.

PMID- 25066092
TI  - Effects of surface treatments and cement types on the bond strength of porcelain
      to-porcelain repair.
AB  - PURPOSE: The purpose of this in vitro study was to evaluate the effects of four
      surface treatments and two resin cements on the repair bond strength of a ceramic
      primer. MATERIALS AND METHODS: Eighty-eight pairs of disks (10 and 5 mm in
      diameter, 3 mm thickness) were prepared from heat-pressed feldspar ceramics (GC
      Initial IQ). After being stored in mucin-artificial saliva for 2 weeks, the 10-mm
      disks were divided into four surface treatment groups (n = 22) and then treated
      as follows: (1) no treatment (control); (2) 40% phosphoric acid; (3) 5%
      hydrofluoric acid + acid neutralizer + 40% phosphoric acid; (4) silica coating
      (CoJet-sand) + 40% phosphoric acid. The 5-mm disks were treated with 5%
      hydrofluoric acid + 40% phosphoric acid. The two sizes of porcelain disks,
      excluding the control group, were primed with Clearfil Ceramic Primer. The
      specimens in each group were further divided into two subgroups of 11 each, and
      bonded with Clearfil Esthetic Cement (CEC) or Panavia F 2.0 Cement (PFC). The
      specimens were stored in distilled water at 37 degrees C for 24 hours,
      thermocycled for 3000 cycles at 5 to 55 degrees C, and stored at 37 degrees C for
      an additional 7 days. Shear bond strength (SBS) was measured with a universal
      testing machine at a 0.5 mm/min crosshead speed until fracture. Statistical
      analysis of the results was carried out with a two-way ANOVA and Tukey HSD test
      (alpha = 0.05). Debonded specimen surfaces were examined under an optical
      microscope to determine the mode of failure. RESULTS: The statistical analysis
      showed that the SBS was significantly affected by surface treatment and resin
      cement (p < 0.05). For treatment groups bonded with CEC, the SBS (MPa) values
      were (1) 2.64 +/- 1.1, (2) 13.31 +/- 3.6, (3) 18.88 +/- 2.6, (4) 14.27 +/- 2.7,
      while for treatment groups cemented with PFC, the SBS (MPa) values were (1) 3.04
      +/- 1.1, (2) 16.44 +/- 3.3, (3) 20.52 +/- 2.2, and (4) 16.24 +/- 2.9. All control
      specimens exhibited adhesive failures, while mixed types of failures were
      observed in phosphoric acid-treated groups. The other groups revealed mainly
      cohesive and mixed failures. CONCLUSIONS: Combined surface treatment of etching
      with hydrofluoric acid and phosphoric acid provides the highest bond strengths to
      porcelain. Also, PFC exhibited higher SBS than CEC did.

PMID- 25066094
TI  - Vemurafenib skin phototoxicity is indirectly linked to ultraviolet A minimal
      erythema dose decrease.
AB  - BACKGROUND: Vemurafenib, an anti-rapidly accelerated fibrosarcoma kinase B (BRAF)
      molecule, improves survival among patients with metastatic BRAF-mutated melanoma.
      Photosensitivity, a frequent cutaneous adverse effect induced by vemurafenib, can
      lead to cessation of treatment. OBJECTIVES: To investigate photosensitivity
      mechanisms in patients treated with vemurafenib for metastatic melanoma. METHODS:
      In a prospective study of 12 patients, photobiological explorations with
      measurements of ultraviolet A (UVA) minimal erythema dose (MED) and polychromatic
      MED were performed over 3 days in all 12 patients. UVA MED and polychromatic MED
      were also assessed for four patients before treatment. We then performed
      spectrophotometric analyses of (i) serum and faeces in these four patients,
      before and after introduction of vemurafenib; (ii) the lyophilized form of
      vemurafenib without excipient added; and (iii) the lyophilized form of
      vemurafenib added to serum and faeces before treatment. RESULTS: Photosensitivity
      was present in 92% of the patients. UVA MED was normal before treatment and
      decreased after treatment, while polychromatic MED remained normal. The same
      three peaks (210, 260 and 310 nm) were identified in the spectrum for UVB and UVC
      but not for UVA on spectrophotometric analyses for each condition (lyophilized
      vemurafenib; serum and faeces after introduction of vemurafenib; and lyophilized
      vemurafenib added to serum and faeces before treatment). The peaks were different
      before treatment. CONCLUSIONS: Our study confirms that photosensitivity under
      vemurafenib treatment was a UVA phototoxicity reaction, and our results suggest
      that a metabolite of vemurafenib rather than the parent molecule is involved in
      this phototoxicity.

PMID- 25066095
TI  - Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia.
AB  - SCOPE: In this study, the effects of punicalagin on neuroinflammation in LPS
      activated microglia were investigated. METHODS AND RESULTS: The ability of
      punicalagin to reduce the production of TNF-alpha, IL-6 and prostaglandin E2 was
      measured in culture medium using enzyme immunoassay. TNF-alpha and IL-6 gene
      expression in mouse hippocampal slices was measured with PCR. cyclooxygenase-2
      and microsomal prostaglandin E synthase 1 protein and mRNA were evaluated with
      Western blotting and PCR, respectively. Further experiments to investigate
      effects of punicalagin on protein expressions of inflammatory targets were also
      determined with Western blotting. Pretreatment of rat primary microglia with
      punicalagin (5-40 MUM) prior to LPS (10 ng/mL) stimulation produced a significant
      (p < 0.05) inhibition of TNF-alpha, IL-6 and prostaglandin E2 production.
      Punicalagin completely abolished TNF-alpha and IL-6 gene expression in LPS
      stimulated hippocampal slices. Protein and mRNA expressions of cyclooxygenase-2
      and microsomal prostaglandin E synthase 1 were also reduced by punicalagin
      pretreatment. Results show that punicalagin interferes with NF-kappaB signalling
      through attenuation of NF-kappaB-driven luciferase expression, as well as
      inhibition of IkappaB phosphorylation and nuclear translocation of p65 subunit in
      the microglia. CONCLUSION: These results suggest that punicalagin inhibits
      neuroinflammation in LPS-activated microglia through interference with NF-kappaB
      signalling, suggesting its potential as a nutritional preventive strategy in
      neurodegenerative disorders.

PMID- 25066096
TI  - Histological recovery and gluten-free diet adherence: a prospective 1-year follow
      up study of adult patients with coeliac disease.
AB  - BACKGROUND: Adequate gluten-free diet (GFD) is the only treatment for coeliac
      disease (CD). However, no agreement has been reached on either how and when to
      assess patient adherence to GFD or its effectiveness on villous atrophy. AIM: To
      assess, in a prospective study, patient adherence to and efficacy of GFD on
      histological recovery after 1-year of GFD. METHODS: Between 2009 and 2012, we
      enrolled 65 consecutive newly-diagnosed adult patients (median age 38 years, 18
      70) with biopsy-proven atrophic CD. Patients were re-evaluated after 1 year of
      GFD with duodenal histology, serological assays, symptoms and a dietary interview
      based on a validated questionnaire. Complete histological recovery was defined as
      the absence of villous atrophy and <=30/100 intraepithelial lymphocytes. RESULTS:
      Overall, 81.5% of patients had adequate adherence (ADA) to GFD, whereas 18.5% had
      an inadequate adherence (IADA); 66% of ADA patients and no IADA patients achieved
      complete histological recovery (P < 0.00001). Among ADA patients, antibody
      seroconversion and symptoms were not significantly different between patients who
      achieved complete histological recovery and those who achieved partial
      histological recovery with P = 0.309 and P = 0.197, respectively. Multivariate
      analysis showed that Marsh 3C was a risk factor for incomplete histological
      recovery in ADA patients (OR 8.74, 95% CI: 1.87-40.83). CONCLUSIONS: This study
      shows that complete histological recovery after 1-year of GFD in adult patients,
      who are assessed as adherent to the GFD, can be obtained in 66% of patients.
      Patients with severe histological damage at diagnosis are at risk for incomplete
      histological recovery 1 year later.

PMID- 25066097
TI  - Novel use for an EGFR mutation-specific antibody in discriminating lung
      adenocarcinoma from reactive pneumocyte hyperplasia.
AB  - AIMS: Pulmonary ground-glass nodules (GGNs) are frequently observed.
      Histopathologically, their presentation can indicate a wide range of disorders
      from an inflammatory process to malignancy. An accurate diagnosis based on GGNs
      can sometimes be challenging on small-sized biopsies. Mutations in the EGFR gene
      are detected in pulmonary adenocarcinomas (ADCs). Immunohistochemical analysis
      using antibodies that detect specific EGFR mutations has been shown to correlate
      with mutational status as determined by molecular methods. We hypothesized that
      these antibodies could be used to discriminate between ADCs and benign pneumocyte
      hyperplasias. METHODS AND RESULTS: Surgically resected, pre-invasive to invasive
      lung ADC (n = 32) and reactive pneumocyte hyperplasia (n = 40) tissue samples
      were probed with antibodies against EGFR mutations, p53, Mouse double minute 2
      and 14-3-3 sigma. Of the 32 lung ADC specimens analysed, 12 (38%) were positive
      using the EGFR mutation-specific antibodies, while no immunoreactivity was
      observed in reactive pneumocyte hyperplasia specimens. Analyses of receiver
      operating characteristic curves showed that the highest area under the curve
      values were associated with the use of EGFR mutation-specific antibodies. In
      addition, a high concordance rate was observed between surgically resected and
      corresponding biopsy materials using these antibodies. CONCLUSIONS: EGFR mutation
      specific antibodies can be used to discriminate between lung ADC and benign
      pneumocyte hyperplasia, even in small-sized biopsies.

PMID- 25066098
TI  - Changes in hormones and biomarkers in polycystic ovarian syndrome treated with
      gastric bypass.
AB  - BACKGROUND: Small retrospective studies have demonstrated reduction in weight and
      co-morbid hirsutism and diabetes in women with polycystic ovary syndrome (PCOS)
      treated with Roux-en-Y gastric bypass. The objective of this study was to
      prospectively determine clinical improvements in obese women with PCOS treated
      with gastric bypass and identify postoperative biomarker changes. METHODS: Data
      were collected on obese women with PCOS undergoing Roux-en-Y gastric bypass over
      1 year. Testosterone, follicle stimulating hormone, lutenizing hormone, insulin,
      fasting glucose, and lipid levels were obtained preoperatively at baseline, and 6
      and 12 months after surgery. Testosterone was used as the primary hormonal
      biomarker. A physical examination for body mass index (BMI) and hirsutism, and
      information on menstrual pattern were collected at baseline and 3, 6, and 12
      months after surgery. RESULTS: Data were available for 14 women. Mean BMI
      decreased from 44.8+/-5.9 kg/m(2) at baseline to 29.2+/-5.9 kg/m(2) at 12 months
      postoperatively. Significant improvements were seen in testosterone, fasting
      glucose, insulin, cholesterol, and triglyceride at 12 months (P<.05). At
      baseline, irregular menses were reported in 10 patients; all patients were
      experiencing regular menses 6 and 12 months after surgery. Hirsutism was present
      in 11 patients at baseline and only 7 patients at 12 months. Improvements in
      biomarkers, menstrual cycling, and hirsutism was not correlated with degree of
      weight change. CONCLUSION: Gastric bypass achieved significant reductions in BMI,
      testosterone, and markers of glucose and lipid metabolism. These data confirm
      reports of previous retrospective studies showing weight reduction and health
      improvement in women with PCOS treated with gastric bypass.

PMID- 25066099
TI  - Comment on: Long-term results after laparoscopic adjustable gastric banding: a
      mean fourteen year follow-up study.

PMID- 25066100
TI  - Does latitude as a zeitgeber affect the course of bipolar affective disorder?
AB  - BACKGROUND: Bipolar disorder (BD) is characterized by recurrent episodes of mood
      dysregulations and depression is considered as the most frequent form of relapse.
      However, there is some evidence that in tropical countries, the course might be
      different with fewer depressive episodes. This study aims to examine the
      frequency of depressive and manic episodes in a sample of subjects with BD from
      India. METHODS: Index subjects and a reliable informant (a family member) were
      interviewed with Diagnostic Interview for Genetic studies and a life chart was
      drawn to ascertain the episodes of illness in addition to reviewing their
      clinical case records. The mean total episode frequency and the mean manic and
      depressive episode frequency were estimated for this study. RESULTS: Data on the
      total episode number and number of manic and depressive episodes separately was
      available in 439 subjects. The subjects had been ill for 7.45 years, had
      experienced an average of 3.29 episodes of mania and 1.08 episodes of depression.
      Thus episodes of mania were seen to be more frequent. CONCLUSION: It has been
      increasingly recognized that circadian rhythm abnormalities could play an
      important role in the relapse and symptom expression of bipolar disorder. The
      mania predominance in the course of BD in this population contrasts from the
      depressive predominance in other studies. We suggest that this phenomenon could
      be a function of latitudinal gradient in the expression of BD using the zeitgeber
      hypothesis.

PMID- 25066101
TI  - Successful liver and lung transplantation in patients with severe IgA deficiency,
      high anti-IgA concentration and a history of anaphylactic transfusion reaction.

PMID- 25066102
TI  - Long-term efficacy of Internet-based cognitive behavior therapy for obsessive
      compulsive disorder with or without booster: a randomized controlled trial.
AB  - BACKGROUND: As relapse after completed cognitive behavior therapy (CBT) for
      obsessive-compulsive disorder (OCD) is common, many treatment protocols include
      booster programs to improve the long-term effects. However, the effects of
      booster programs are not well studied. In this study, we investigated the long
      term efficacy of Internet-based CBT (ICBT) with therapist support for OCD with or
      without an Internet-based booster program. METHOD: A total of 101 participants
      were included in the long-term follow-up analysis of ICBT. Of these, 93 were
      randomized to a booster program or no booster program. Outcome assessments were
      collected at 4, 7, 12 and 24 months after receiving ICBT. RESULTS: The entire
      sample had sustained long-term effects from pre-treatment to all follow-up
      assessments, with large within-group effect sizes (Cohen's d = 1.58-2.09). The
      booster group had a significant mean reduction in OCD symptoms compared to the
      control condition from booster baseline (4 months) to 7 months, but not at 12 or
      24 months. Participants in the booster group improved significantly in terms of
      general functioning at 7, 12 and 24 months, and had fewer relapses. Kaplan-Meier
      analysis also indicated a significantly slower relapse rate in the booster group.
      CONCLUSIONS: The results suggest that ICBT has sustained long-term effects and
      that adding an Internet-based booster program can further improve long-term
      outcome and prevent relapse for some OCD patients.

PMID- 25066105
TI  - Thermopower enhancement by fractional layer control in 2D oxide superlattices.
AB  - Precise tuning of the 2D carrier density by using fractional delta-doping of d
      electrons improves the thermoelectric properties of oxide heterostructures. This
      promising result can be attributed to the anisotropic band structure in the 2D
      system, indicating that delta-doped oxide superlattices are good candidates for
      advanced thermoelectrics.

PMID- 25066103
TI  - Advances in urea cycle neuroimaging: Proceedings from the 4th International
      Symposium on urea cycle disorders, Barcelona, Spain, September 2013.
AB  - Our previous imaging research performed as part of a Urea Cycle Rare Disorders
      Consortium (UCRDC) grant, has identified specific biomarkers of neurologic injury
      in ornithine transcarbamylase deficiency, OTCD. While characterization of
      mutations can be achieved in most cases, this information does not necessarily
      predict the severity of the underlying neurological syndrome. The biochemical
      consequences of any mutation may be modified additionally by a large number of
      factors, including contributions of other enzymes and transport systems that
      mediate flux through the urea cycle, diet and other environmental factors. These
      factors likely vary from one patient to another, and they give rise to
      heterogeneity of clinical severity. Affected cognitive domains include non-verbal
      learning, fine motor processing, reaction time, visual memory, attention, and
      executive function. Deficits in these capacities may be seen in symptomatic
      patients, as well as asymptomatic carriers with normal IQ and correlate with
      variances in brain structure and function in these patients. Using neuroimaging
      we can identify biomarkers that reflect the downstream impact of UCDs on
      cognition. This manuscript is a summary of the presentation from the 4th
      International Consortium on urea cycle disorders held in, Barcelona, Spain,
      September 2, 2014. 

PMID- 25066104
TI  - Succinylacetone as primary marker to detect tyrosinemia type I in newborns and
      its measurement by newborn screening programs.
AB  - Tyrosinemia type I (TYR I) is caused by autosomal recessive fumarylacetoacetate
      hydrolase deficiency and is characterized by development of severe liver disease
      in infancy and neurologic crises. If left untreated, most patients die of liver
      failure in the first years of life. Intervention with medication is effective
      when initiated during the first month of life. This improvement in the treatment
      of TYR I patients influenced the decision to include TYR I in the US Secretary of
      the Department of Health and Human Services' (HHS) Recommended Uniform Screening
      Panel. However, while tyrosine is routinely measured in newborn screening (NBS)
      by tandem mass spectrometry (MS/MS), elevated tyrosine levels are not specific to
      TYR I. To improve the specificity of NBS for TYR I, several assays were developed
      to measure succinylacetone (SUAC) in dried blood spots (DBS). SUAC is a
      pathognomonic marker of TYR I, and its detection by NBS MS/MS is possible. This
      review of the current status of NBS for TYR I in the US is the result of
      discussions at the HHS Secretary's (Discretionary) Advisory Committee on
      Heritable Disorders in Newborns and Children about the inconsistent
      implementation of effective NBS for TYR I in the US. We sought to understand the
      different TYR I screening practices in US NBS programs. Results indicate that 50
      out of 51 NBS programs in the US screen for TYR I, and a successful SUAC
      performance evaluation scheme is available from the Centers for Disease Control
      and Prevention. Programmatic and methodological barriers were identified that
      prevent widespread adoption of SUAC measurements in NBS laboratories. However,
      since SUAC detection is currently the best approach to NBS for TYR I, a further
      delay of the addition of SUAC measurement into NBS procedures is discouraged.
      SUAC measurement should improve both the false positive and false negative rate
      in NBS for TYR I thereby yielding the desired benefits for affected patients at
      no expense to the overall population served. 

PMID- 25066106
TI  - Genomics of invasion: diversity and selection in introduced populations of
      monkeyflowers (Mimulus guttatus).
AB  - Global trade and travel is irreversibly changing the distribution of species
      around the world. Because introduced species experience drastic demographic
      events during colonization and often face novel environmental challenges from
      their native range, introduced populations may undergo rapid evolutionary change.
      Genomic studies provide the opportunity to investigate the extent to which
      demographic, historical and selective processes shape the genomic structure of
      introduced populations by analysing the signature that these processes leave on
      genomic variation. Here, we use next-generation sequencing to compare genome-wide
      relationships and patterns of diversity in native and introduced populations of
      the yellow monkeyflower (Mimulus guttatus). Genome resequencing data from 10
      introduced populations from the United Kingdom (UK) and 12 native M. guttatus
      populations in North America (NA) demonstrated reduced neutral genetic diversity
      in the introduced range and showed that UK populations are derived from a
      geographic region around the North Pacific. A selective-sweep analysis revealed
      site frequency changes consistent with selection on five of 14 chromosomes, with
      genes in these regions showing reduced silent site diversity. While the target of
      selection is unknown, genes associated with flowering time and biotic and abiotic
      stresses were located within the swept regions. The future identification of the
      specific source of origin of introduced UK populations will help determining
      whether the observed selective sweeps can be traced to unsampled native
      populations or occurred since dispersal across the Atlantic. Our study
      demonstrates the general potential of genome-wide analyses to uncover a range of
      evolutionary processes affecting invasive populations.

PMID- 25066108
TI  - Awareness of Stress-reduction Interventions: The Impact on Employees' Well-being
      and Organizational Attitudes.
AB  - Employing the social-exchange theoretical framework, we examined the effect of
      employees' awareness of stress-reduction interventions on their levels of
      psychological strain, job satisfaction, organizational commitment, perceptions of
      senior management trustworthiness and procedural justice. We present longitudinal
      panel data from 869 employees who completed questionnaires at two time points at
      13 Australian universities. Our results show that employees who reported an
      awareness of stress-reduction interventions undertaken at their university scored
      lower on psychological strain and higher on job satisfaction and commitment than
      those who were unaware of the interventions. The results suggest that simply the
      awareness of stress interventions can be linked to positive employee outcomes.
      The study further revealed that senior management trustworthiness and procedural
      justice mediate the relationship between awareness and employee outcomes.
      Copyright (c) 2014 John Wiley & Sons, Ltd. 

PMID- 25066107
TI  - A cross-sectional study of the relationship between serum liver enzymes level and
      the incidence of impaired fasting glucose in males and females.
AB  - BACKGROUND: The aim of this study was to investigate the possible correlation
      between levels of serum liver enzymes and impaired fasting glucose (IFG) in
      Chinese adults and to provide a new perspective for the prevention of pre
      diabetes. MATERIAL/METHODS: Serum liver enzymes of the samples including alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and g-glutamyl
      transferase (GGT), as well as plasma glucose, blood lipids, and insulin, were
      measured. The cumulative incidences of IFG between different quartiles of liver
      enzymes were compared by the chi-square test. A logistic regression model (binary
      regression) was used to calculate the odds ratio (OR) of IFG with 95% confidence
      interval (95% CI). RESULTS: The total incidence of IFG was 20.3% and the
      cumulative incidence of IFG was higher in men compared to women. In both sexes,
      IFG is more prevalent in higher quartiles of liver enzymes. After adjusting for
      age, BMI, blood pressure, triglycerides (TG), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total
      cholesterol (TC), the cumulative incidences of IFG were significantly higher in
      the highest quartiles of liver enzymes than in the lowest quartiles. A
      significantly higher cumulative incidence of IFG was found in the highest GGT
      quartile than in the lowest quartile for woman. CONCLUSIONS: The results of this
      study suggest that serum liver enzymes are related to the risk of IFG in Chinese
      adults. We infer that preserving the hepatic function may be an efficient way to
      prevent the development of IFG, especially in males.

PMID- 25066109
TI  - GLP-1 receptor agonists: effects on the progression of non-alcoholic fatty liver
      disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver
      diseases, and its incidence has been increasing recently. In addition to hepatic
      complications, NAFLD is also recognized as an independent risk factor for
      cardiovascular disease. Unfortunately, the current therapies for NAFLD display
      variable efficacy; a novel and effective drug is urgently needed. Glucagon-like
      peptide-1 (GLP-1), a receptor agonist is a new drug approved for treating type 2
      diabetes. Recently, these types of agents have shown a novel therapeutic effect
      on NAFLD. However, the mechanisms of GLP-1 receptor agonists on the treatment of
      NAFLD have not yet been explained precisely. Recent studies have demonstrated
      that GLP-1 reverses the progression of NAFLD not only indirectly through an
      incretin effect that improves key parameters involved in NAFLD, but also a direct
      effect on lipid metabolism of hepatocytes and inflammation in liver. In this
      review, we provided an overview of the role and mechanisms of GLP-1 in the
      therapy of NAFLD.

PMID- 25066110
TI  - Implicating the role of lycopene in restoration of mitochondrial enzymes and BDNF
      levels in beta-amyloid induced Alzheimer's disease.
AB  - Lycopene has attracted significant research interest due to its beneficial
      therapeutic effects, which include anti-oxidant, neuro-protective and anti-cancer
      effects, but the mechanisms of its beneficial action are not clear so far. The
      present study was carried out to elucidate the neuroprotective effect of lycopene
      against the beta-amyloid induced cognitive impairment and mitochondria oxidative
      damage in rats. beta-amyloid (beta-A1-42) was administered through
      intracerebroventricular (ICV) by using stereotaxic instrument in male Wistar
      rats. Lycopene (2.5 and 5mg/kg) was administrated for three weeks. Behavioral
      performances were conducted during the study. The rats were sacrificed on the
      21st day following the last behavioral test and cytoplasmic fractions of
      hippocampus were prepared for the quantification of acetylcholinesterase,
      oxidative stress parameter, mitochondrial enzymes, and inflammatory mediator like
      TNF-alpha, Il-6 activities, caspase-3 and BDNF. ICV beta-A1-42 resulted in poor
      memory retention in Morris water maze and caused marked oxidative stress as
      indicated by significant increase in oxidative, mitochondria damage, TNF-alpha,
      IL-6 and Caspase-3 activity. We also found that beta-A1-42 induced animal altered
      BDNF level than control animals. Chronic administration of lycopene resulted in
      an improvement in memory retention, attenuation of mitochondrial-oxidative
      damage, reduced neuro-inflammation and restoration of BDNF level in beta-A1-42
      treated rats. These studies indicated that lycopene helps to protect beta-A1-42
      induced cognitive dysfunction and modulates amyloidogenesis. 

PMID- 25066111
TI  - Endothelial progenitor cells in diabetic patients with myocardial infarction -
      can statins improve their function?
AB  - The effect of statins on endothelial progenitor cells (EPCs) function derived
      from diabetic patients (DMpts) with acute myocardial infarction (AMI) is unknown.
      In this study we assess the response of early and late EPCs from diabetic versus
      non-diabetic patients (NDMpts) with AMI to statins. EPCs were obtained from 10
      diabetic and 10 age-matched non-diabetic male patients with AMI. For each
      patient, cultures of early and late EPCs were performed under 4 different
      conditions: normal glucose concentration (control); high glucose concentration;
      normal glucose concentration with atorvastatin supplementation and normal glucose
      concentration with pravastatin supplementation. To compare the effect of these
      treatments on EPC function in DMpts versus NDMpts, we performed in vitro: EPC
      colony-forming units (CFU) assay; cell cycle analysis; viability assessment and
      expression of the surface markers CXCR4, CD133, CD34 and KDR. Under control
      conditions, CFU numbers were reduced in DMpts-derived EPCs when compared to those
      of NDMpts (1.4+/-0.8 vs 2.6+/-1.2 CFU/well, P=0.021). When early EPCs from DMpts
      were cultured in the presence of statins, CFU capacity was restored, surmounting
      that of NDMpts under control conditions. Statins significantly improved viability
      of early EPCs and delayed the onset of late EPCs senescence, even in cells from
      DMpts. In addition, statins induced approximately a 2-fold increase in the
      proportion of late EPCs in S-phase of the cell cycle (P<0.05). Statins have a
      beneficial effect on both early and late EPCs from DMpts with AMI. Despite the
      functional impairment of EPCs from DMpts, they exhibit similar responsiveness to
      statins as equivalent cells from NDMpts. 

PMID- 25066112
TI  - Silybin reduces obliterated retinal capillaries in experimental diabetic
      retinopathy in rats.
AB  - Silybin has been previously reported to possess anti-inflammatory properties,
      raising the possibility that it may reduce vascular damage in diabetic
      retinopathy. Present study was designed to investigate this potential effect of
      silybin and its underlying mechanisms in experimental diabetic retinopathy.
      Diabetes was induced with streptozotocin (STZ) plus high-fat diet in Sprague
      Dawley rats, and silybin was administrated for 22 weeks after the induction of
      diabetes. Histochemical and immunofluorescence techniques were used to assess the
      obliterated retinal capillaries, leukostasis, and level of retinal intercellular
      adhesion molecule-1 (ICAM-1). Western blot was performed to quantitate the
      expression of retinal ICAM-1. Results showed that silybin treatment significantly
      prevented the development of obliterated retinal capillaries in diabetes,
      compared with vehicle treatment. In addition, leukostasis and level of the
      retinal ICAM-1 were found to decrease considerably in silybin-treated diabetic
      groups. In conclusion, these results indicate that silybin reduces obliterated
      retinal capillaries in experimental diabetes, and the recovered retinal vascular
      leukostasis and level of ICAM-1 at least partly contributes to the preventive
      effect of silybin. 

PMID- 25066113
TI  - Indirubin derivatives alter DNA binding activity of the transcription factor NF-Y
      and inhibit MDR1 gene promoter.
AB  - Indirubin derivatives exert antitumor activity. However, their effects on the
      expression of multidrug resistance gene 1 (MDR1) have not been investigated. Here
      we found three derivatives that inhibit the MDR1 gene promoter. To investigate
      the effects of indirubins on the DNA binding of NF-Y, a major MDR1 gene
      transcription factor that recognizes an inverted CCAAT element in the promoter,
      gel mobility shift assay was performed using the element as a probe with nuclear
      extracts from NG108-15, MCF7, HepG2, C2C12, and SK-N-SH cells. Among 17
      compounds, 5-methoxyindirubin inhibited the DNA binding of NF-Y significantly,
      whereas indirubin-3'-oxime and 7-methoxyindirubin 3'-oxime increased the binding
      considerably. After evaluating a suitable concentration of each compound for
      transcription analysis using living tumor cells, we performed a reporter gene
      assay using a reporter DNA plasmid containing EGFP cDNA fused to the MDR1 gene
      promoter region. Indirubin-3'-oxime exerted a significant inhibitory effect on
      the MDR1 promoter activity in MCF7 and HepG2 cells, and 5-methoxyindirubin
      inhibited the activity only in MCF7 cells; 7-methoxyindirubin 3'-oxime suppressed
      the activity in all of the cell lines. We further confirmed that the compounds
      reduced endogenous MDR1 transcription without any inhibitory effect on NF-Y
      expression. Moreover, each compound increased the doxorubicin sensitivity of MCF7
      cells. These results indicate that each indirubin derivative acts on the DNA
      binding of NF-Y and represses the MDR1 gene promoter with tumor cell-type
      specificity. 

PMID- 25066114
TI  - Protective and biogenesis effects of sodium hydrosulfide on brain mitochondria
      after cardiac arrest and resuscitation.
AB  - Mitochondrial dysfunction plays a critical role in brain injury after cardiac
      arrest and cardiopulmonary resuscitation (CPR). Recent studies demonstrated that
      hydrogen sulfide (H2S) donor compounds preserve mitochondrial morphology and
      function during ischemia-reperfusion injury. In this study, we sought to explore
      the effects of sodium hydrosulfide (NaHS) on brain mitochondria 24h after cardiac
      arrest and resuscitation. Male Sprague-Dawley rats were subjected to 6min cardiac
      arrest and then resuscitated successfully. Rats received NaHS (0.5mg/kg) or
      vehicle (0.9% NaCl, 1.67ml/kg) 1min before the start of CPR intravenously,
      followed by a continuous infusion of NaHS (1.5mg/kg/h) or vehicle (5ml/kg/h) for
      3h. Neurological deficit was evaluated 24h after resuscitation and then cortex
      was collected for assessments. As a result, we found that rats treated with NaHS
      revealed an improved neurological outcome and cortex mitochondrial morphology 24h
      after resuscitation. We also observed that NaHS therapy reduced intracellular
      reactive oxygen species generation and calcium overload, inhibited mitochondrial
      permeability transition pores, preserved mitochondrial membrane potential,
      elevated ATP level and ameliorated the cytochrome c abnormal distribution.
      Further studies indicated that NaHS administration increased mitochondrial
      biogenesis in cortex at the same time. Our findings suggested that administration
      of NaHS 1min prior CPR and followed by a continuous infusion ameliorated
      neurological dysfunction 24h after resuscitation, possibly through mitochondria
      preservation as well as by promoting mitochondrial biogenesis. 

PMID- 25066115
TI  - Substance use disorders and co-morbidities among Asian Americans and Native
      Hawaiians/Pacific Islanders.
AB  - BACKGROUND: Asian Americans (AAs) and Native Hawaiians/Pacific Islanders
      (NHs/PIs) are the fastest growing segments of the US population. However, their
      population sizes are small, and thus AAs and NHs/PIs are often aggregated into a
      single racial/ethnic group or omitted from research and health statistics. The
      groups' substance use disorders (SUDs) and treatment needs have been under
      recognized. METHOD: We examined recent epidemiological data on the extent of
      alcohol and drug use disorders and the use of treatment services by AAs and
      NHs/PIs. RESULTS: NHs/PIs on average were less educated and had lower levels of
      household income than AAs. Considered as a single group, AAs and NHs/PIs showed a
      low prevalence of substance use and disorders. Analyses of survey data that
      compared AAs and NHs/PIs revealed higher prevalences of substance use (alcohol,
      drugs), depression and delinquency among NHs than among AAs. Among treatment
      seeking patients in mental healthcare settings, NHs/PIs had higher prevalences of
      DSM-IV diagnoses than AAs (alcohol/drug, mood, adjustment, childhood-onset
      disruptive or impulse-control disorders), although co-morbidity was common in
      both groups. AAs and NHs/PIs with an SUD were unlikely to use treatment,
      especially treatment for alcohol problems, and treatment use tended to be related
      to involvement with the criminal justice system. CONCLUSIONS: Although available
      data are limited by small sample sizes of AAs and NHs/PIs, they demonstrate the
      need to separate AAs and NHs/PIs in health statistics and increase research into
      substance use and treatment needs for these fast-growing but understudied
      population groups.

PMID- 25066116
TI  - A chemically standardized extract of Ziziphus jujuba fruit (Jujube) stimulates
      expressions of neurotrophic factors and anti-oxidant enzymes in cultured
      astrocytes.
AB  - The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly
      consumed as a health supplement worldwide. To study the role of jujube in brain
      benefits, the expression of neurotrophic factors and anti-oxidant enzymes in the
      jujube-treated cultured astrocytes was determined. Application of a chemical
      standardized water extract of jujube in cultured astrocytes for 24 h stimulated
      the expressions of nerve growth factor, brain-derived neurotrophic factor and
      glial cell line-derived neurotrophic factor in a concentration-dependent manner.
      The pre-treatment with H89, a protein kinase A inhibitor, attenuated the jujube
      induced expression of neurotrophic factors. In parallel, the treatment of jujube
      water extract induced the transcriptional expressions of the enzymes responsible
      for anti-oxidation, i.e. NAD(P)H: quinine oxidoreductase 1, glutamate-cysteine
      ligase catalytic subunit, glutamate-cysteine ligase modifier subunit and
      glutathione S-transferase, in a concentration-dependent manner. These results
      proposed the benefits of jujube in regulating expressions of neurotrophic factors
      and anti-oxidant enzymes in cultured astrocytes.

PMID- 25066117
TI  - Prevalence of cardiovascular health risk behaviors in a remote rural community of
      Sindhuli district, Nepal.
AB  - BACKGROUND: Cardiovascular disease (CVD) is emerging as a public health menace
      among low and middle income countries. It has particularly affected the poorest.
      However, there is paucity of information about CVD risk factors profile among
      Nepalese rural communities where the majority of people live in poverty.
      Therefore, this study aimed to identify the prevalence of cardiovascular health
      risk behaviors in an outback community of Nepal. METHODS: We conducted a
      descriptive cross-sectional study in Tinkanya Village Development Committee
      (VDC), Sindhuli between January and March, 2014. Total 406 participants of age 20
      to 50 years were selected randomly. Data were collected using WHO-NCD STEPwise
      approach questionnaires and analyzed with SPSS V.16.0 and R i386 2.15.3 software.
      RESULT: The mean age of participants was 36.2 +/- 9 years. Majority of
      participants (76.3%) were from lower socio-economic class, Adibasi/Janajati
      (63.1%), and without formal schooling (46.3%). Smoking was present in 28.6%,
      alcohol consumption in 47.8%, insufficient fruits and vegetables intake in 96.6%,
      insufficient physical activity in 48.8%; 25.6% had high waist circumference,
      37.4% had overweight and obesity. Average daily salt intake per capita was 14.4
      grams +/-4.89 grams. Hypertension was detected in 12.3%. It had an inverse
      relationship with education and socio-economic status. In binary logistic
      regression analysis, age, smoking, body mass index (BMI) and daily salt intake
      were identified as significant predictors of hypertension. CONCLUSION: Present
      study showed high prevalence of smoking, alcohol consumption, insufficient fruit
      and vegetable intake, daily salt intake, overweight and obesity and hypertension
      among remote rural population suggesting higher risk for developing CVD in
      future. Nepalese rural communities, therefore, are in need of population-wide
      comprehensive intervention approaches for reducing CVD health risk behaviors.

PMID- 25066118
TI  - Community-acquired diarrhea associated with Clostridium difficile in an HIV
      positive cancer patient: first case report in Latin America.
AB  - Clostridium difficile is the most important cause of nosocomial diarrhea, mainly
      associated with antibiotic use and immunodeficiency. Although, an increased
      incidence of community-acquired C. difficile infection (CA-CDI) has been reported
      worldwide, this infection has been under-diagnosed in Latin America. This is the
      first report of a CA-CDI case in Latin America, in an HIV-positive patient with
      cancer. 

PMID- 25066119
TI  - The BRCA1-interacting protein Abraxas is required for genomic stability and tumor
      suppression.
AB  - Germline mutations of BRCA1 confer hereditary susceptibility to breast and
      ovarian cancer. However, somatic mutation of BRCA1 is infrequent in sporadic
      breast cancers. The BRCA1 protein C terminus (BRCT) domains interact with
      multiple proteins and are required for BRCA1's tumor-suppressor function. In this
      study, we demonstrated that Abraxas, a BRCA1 BRCT domain-interacting protein,
      plays a role in tumor suppression. Abraxas exerts its function through binding to
      BRCA1 to regulate DNA repair and maintain genome stability. Both homozygous and
      heterozygous Abraxas knockout mice exhibited decreased survival and increased
      tumor incidence. The gene encoding Abraxas suffers from gene copy loss and
      somatic mutations in multiple human cancers including breast, ovarian, and
      endometrial cancers, suggesting that mutation and loss of function of Abraxas may
      contribute to tumor development in human patients.

PMID- 25066120
TI  - PGC1beta activates an antiangiogenic program to repress neoangiogenesis in muscle
      ischemia.
AB  - Revascularization of ischemic skeletal muscle is governed by a balance between
      pro- and antiangiogenic factors in multiple cell types but particularly in
      myocytes and endothelial cells. Whereas the regulators of proangiogenic factors
      are well defined (e.g., hypoxia-inducible factor [HIF]), the transcriptional
      pathways encoding antiangiogenic factors remain unknown. We report that the
      transcriptional cofactor PGC1beta drives an antiangiogenic gene program in muscle
      and endothelial cells. PGC1beta transcriptionally represses proangiogenic genes
      (e.g., Vegfc, Vegfd, Pdgfb, Angpt1, Angpt2, Fgf1, and Fgf2) and induces
      antiangiogenic genes (e.g., Thbs1, Thbs2, Angstat, Pedf, and Vash1).
      Consequently, muscle-specific PGC1beta overexpression impairs muscle
      revascularization in ischemia and PGC1beta deletion enhances it. PGC1beta
      overexpression or deletion in endothelial cells also blocks or stimulates
      angiogenesis, respectively. PGC1beta stimulates the antiangiogenic genes partly
      by coactivating COUP-TFI. Furthermore, proangiogenic stimuli such as hypoxia,
      hypoxia-mimetic agents, and ischemia decrease PGC1beta expression in a HIF
      dependent manner. PGC1beta is an antiangiogenic transcriptional switch that could
      be targeted for therapeutic angiogenesis. 

PMID- 25066121
TI  - A mitochondrial switch promotes tumor metastasis.
AB  - Metastatic progression of cancer is associated with poor outcome, and here we
      examine metabolic changes underlying this process. Although aerobic glycolysis is
      known to promote metastasis, we have now identified a different switch primarily
      affecting mitochondria. The switch involves overload of the electron transport
      chain (ETC) with preserved mitochondrial functions but increased mitochondrial
      superoxide production. It provides a metastatic advantage phenocopied by partial
      ETC inhibition, another situation associated with enhanced superoxide production.
      Both cases involved protein tyrosine kinases Src and Pyk2 as downstream
      effectors. Thus, two different events, ETC overload and partial ETC inhibition,
      promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and
      metastasis. Consequently, specific scavenging of mitochondrial superoxide with
      mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis
      in murine and human tumor models. 

PMID- 25066122
TI  - Heterogeneous tumor subpopulations cooperate to drive invasion.
AB  - Clonal selection and transcriptional reprogramming (e.g., epithelial-mesenchymal
      transition or phenotype switching) are the predominant theories thought to
      underlie tumor progression. However, a "division of labor" leading to cooperation
      among tumor-cell subpopulations could be an additional catalyst of progression.
      Using a zebrafish-melanoma xenograft model, we found that in a heterogeneous
      setting, inherently invasive cells, which possess protease activity and deposit
      extracellular matrix (ECM), co-invade with subpopulations of poorly invasive
      cells, a phenomenon we term "cooperative invasion". Whereas the poorly invasive
      cells benefit from heterogeneity, the invasive cells switch from protease
      independent to an MT1-MMP-dependent mode of invasion. We did not observe changes
      in expression of the melanoma phenotype determinant MITF during cooperative
      invasion, thus ruling out the necessity for phenotype switching for invasion.
      Altogether, our data suggest that cooperation can drive melanoma progression
      without the need for clonal selection or phenotype switching and can account for
      the preservation of heterogeneity seen throughout tumor progression. 

PMID- 25066123
TI  - CC2D1A regulates human intellectual and social function as well as NF-kappaB
      signaling homeostasis.
AB  - Autism spectrum disorder (ASD) and intellectual disability (ID) are often
      comorbid, but the extent to which they share common genetic causes remains
      controversial. Here, we present two autosomal-recessive "founder" mutations in
      the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to
      severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms.
      CC2D1A regulates multiple intracellular signaling pathways, and we found its
      strongest effect to be on the transcription factor nuclear factor kappaB (NF
      kappaB). Cc2d1a gain and loss of function both increase activation of NF-kappaB,
      revealing a critical role of Cc2d1a in homeostatic control of intracellular
      signaling. Cc2d1a knockdown in neurons reduces dendritic complexity and increases
      NF-kappaB activity, and the effects of Cc2d1a depletion can be rescued by
      inhibiting NF-kappaB activity. Homeostatic regulation of neuronal signaling
      pathways provides a mechanism whereby common founder mutations could manifest
      diverse symptoms in different patients. 

PMID- 25066124
TI  - Complement-dependent modulation of antitumor immunity following radiation
      therapy.
AB  - Complement is traditionally thought of as a proinflammatory effector mechanism of
      antitumor immunity. However, complement is also important for effective clearance
      of apoptotic cells, which can be an anti-inflammatory and tolerogenic process. We
      show that localized fractionated radiation therapy (RT) of subcutaneous murine
      lymphoma results in tumor cell apoptosis and local complement activation.
      Cotreatment of mice with tumor-targeted complement inhibition markedly improved
      therapeutic outcome of RT, an effect linked to early increases in apoptotic cell
      numbers and increased inflammation. Improved outcome was dependent on an early
      neutrophil influx and was characterized by increased numbers of mature dendritic
      cells and the subsequent modulation of T cell immunity. Appropriate complement
      inhibition may be a promising strategy to enhance a mainstay of treatment for
      cancer. 

PMID- 25066125
TI  - Zinc binding directly regulates tau toxicity independent of tau
      hyperphosphorylation.
AB  - Tau hyperphosphorylation is thought to underlie tauopathy. Working in a
      Drosophila tauopathy model expressing a human Tau mutant (hTauR406W, or Tau(*)),
      we show that zinc contributes to the development of Tau toxicity through two
      independent actions: by increasing Tau phosphorylation and, more significantly,
      by directly binding to Tau. Elimination of zinc binding through amino acid
      substitution of Cys residues has a minimal effect on phosphorylation levels yet
      essentially eliminates Tau toxicity. The toxicity of the zinc-binding-deficient
      mutant Tau(*) (Tau(*)C2A) and overexpression of native Drosophila Tau, also
      lacking the corresponding zinc-binding Cys residues, are largely impervious to
      zinc concentration. Importantly, restoration of zinc-binding ability to Tau(*) by
      introduction of a zinc-binding residue (His) into the original Cys positions
      restores zinc-responsive toxicities in proportion to zinc-binding affinities.
      These results indicate zinc binding is a substantial contributor to tauopathy and
      have implications for therapy development. 

PMID- 25066126
TI  - Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive
      prostate cancer.
AB  - Despite much evidence on epigenetic abnormalities in cancer, it is currently
      unclear to what extent epigenetic alterations can be associated with tumors'
      clonal genetic origins. Here, we show that the prostate intratumor heterogeneity
      in DNA methylation and copy-number patterns can be explained by a unified
      evolutionary process. By assaying multiple topographically distinct tumor sites,
      premalignant lesions, and lymph node metastases within five cases of prostate
      cancer, we demonstrate that both DNA methylation and copy-number heterogeneity
      consistently reflect the life history of the tumors. Furthermore, we show cases
      of genetic or epigenetic convergent evolution and highlight the diversity in the
      evolutionary origins and aberration spectrum between tumor and metastatic
      subclones. Importantly, DNA methylation can complement genetic data by serving as
      a proxy for activity at regulatory domains, as we show through identification of
      high epigenetic heterogeneity at androgen-receptor-bound enhancers. Epigenome
      variation thereby expands on the current genome-centric view on tumor
      heterogeneity.

PMID- 25066127
TI  - Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a.
AB  - DNA methylation is a central epigenetic modification that is established by de
      novo DNA methyltransferases. The mechanisms underlying the generation of genomic
      methylation patterns are still poorly understood. Using mass spectrometry and a
      phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates
      endogenous Dnmt3a at two key residues located near its PWWP domain, thereby
      downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA
      methylation analysis shows that CK2 primarily modulates CpG methylation of
      several repeats, most notably of Alu SINEs. This modulation can be directly
      attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2
      mediated phosphorylation is required for localization of Dnmt3a to
      heterochromatin. By revealing phosphorylation as a mode of regulation of de novo
      DNA methyltransferase function and by uncovering a mechanism for the regulation
      of methylation at repetitive elements, our results shed light on the origin of
      DNA methylation patterns. 

PMID- 25066128
TI  - A myeloperoxidase-containing complex regulates neutrophil elastase release and
      actin dynamics during NETosis.
AB  - Neutrophils contain granules loaded with antimicrobial proteins and are regarded
      as impermeable organelles that deliver cargo via membrane fusion. However, during
      the formation of neutrophil extracellular traps (NETs), neutrophil elastase (NE)
      translocates from the granules to the nucleus via an unknown mechanism that does
      not involve membrane fusion and requires reactive oxygen species (ROS). Here, we
      show that the ROS triggers the dissociation of NE from a membrane-associated
      complex into the cytosol and activates its proteolytic activity in a
      myeloperoxidase (MPO)-dependent manner. In the cytosol, NE first binds and
      degrades F-actin to arrest actin dynamics and subsequently translocates to the
      nucleus. The complex is an example of an oxidative signaling scaffold that
      enables ROS and antimicrobial proteins to regulate neutrophil responses.
      Furthermore, granules contain protein machinery that transports and delivers
      cargo across membranes independently of membrane fusion.

PMID- 25066129
TI  - Discovering protein-protein interactions within the programmed cell death network
      using a protein-fragment complementation screen.
AB  - Apoptosis and autophagy are distinct biological processes, each driven by a
      different set of protein-protein interactions, with significant crosstalk via
      direct interactions among apoptotic and autophagic proteins. To measure the
      global profile of these interactions, we adapted the Gaussia luciferase protein
      fragment complementation assay (GLuc PCA), which monitors binding between
      proteins fused to complementary fragments of a luciferase reporter. A library
      encompassing 63 apoptotic and autophagic proteins was constructed for the
      analysis of ~3,600 protein-pair combinations. This generated a detailed landscape
      of the apoptotic and autophagic modules and points of interface between them,
      identifying 46 previously unknown interactions. One of these interactions,
      between DAPK2, a Ser/Thr kinase that promotes autophagy, and 14-3-3tau, was
      further investigated. We mapped the region responsible for 14-3-3tau binding and
      proved that this interaction inhibits DAPK2 dimerization and activity. This proof
      of concept underscores the power of the GLuc PCA platform for the discovery of
      biochemical pathways within the cell death network.

PMID- 25066130
TI  - Disruption of Runx1 and Runx3 leads to bone marrow failure and leukemia
      predisposition due to transcriptional and DNA repair defects.
AB  - The RUNX genes encode transcription factors involved in development and human
      disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis
      for their involvement in leukemogenesis is not fully understood. Here, we show
      that Runx1;Runx3 double-knockout (DKO) mice exhibited lethal phenotypes due to
      bone marrow failure and myeloproliferative disorder. These contradictory clinical
      manifestations are reminiscent of human inherited bone marrow failure syndromes
      such as Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3
      DKO cells showed mitomycin C hypersensitivity, due to impairment of
      monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2
      monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact
      with FANCD2 independently of CBFbeta, suggesting a nontranscriptional role for
      RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA
      repair defect, besides transcriptional misregulation, and promotes the
      development of leukemias and other cancers. 

PMID- 25066131
TI  - Stenting versus surgery for atrial-esophageal fistula.

PMID- 25066132
TI  - From experimental design to functional gene networks: DNA microarray contribution
      to skin ageing research.
AB  - There is no doubt that the DNA microarray-based technology contributed to
      increase our knowledge of a wide range of processes. However, integrating genes
      into functional networks, rather than terms describing generic characteristics,
      remains an important challenge. The highly context-dependent function of a given
      gene and feedback mechanisms complexify greatly the interpretation of the data.
      Moreover, it is difficult to determine whether changes in gene expression are the
      result or the cause of pathologies or physiological events. In both cases, the
      difficulty relies on the involvement of processes that, at an early stage, can be
      protective and later on, deleterious because of their runaway. Each individual
      cell has its own transcription profile that determines its behaviour and its
      relationships with its neighbours. This is particularly true when a mechanism
      such as cell cycle is concerned. Another issue concerns the analyses from samples
      of different donors. Whereas the statistical tools lead to determine common
      features among groups, they tend to smooth the overall data and consequently, the
      selected values represent the 'tip of the iceberg'. There is a significant
      overlap in the set of genes identified in the different studies on skin ageing
      processes described in the present review. The reason of this overlap is because
      most of these genes belong to the basic machinery controlling cell growth and
      arrest. To get a more full picture of these processes, a hard work has still to
      be done to determine the precise mechanisms conferring the cell type specificity
      of ageing. Integrative biology applied to the huge amount of existing microarray
      data should fulfil gaps, through the characterization of additional actors
      accounting for the activation of specific signalling pathways at crossing points.
      Furthermore, computational tools have to be developed taking into account that
      expression values among similar groups may not vary 'by chance' but may reflect,
      along with other subtle changes, specific features of one given donor. Through a
      better stratification, these tools will allow to recover genes from the 'bottom
      of the iceberg'. Identifying these genes should contribute to understand how skin
      ages among individuals, thus paving the way for personalized skin care. 

PMID- 25066133
TI  - Temporal effects of vascular endothelial growth factor and 3,5-cyclic
      monophosphate on blood-brain barrier solute permeability in vivo.
AB  - To test the hypothesis that vascular endothelial growth factor (VEGF) can
      transiently increase the blood-brain barrier permeability, P, as for peripheral
      microvessels and that the elevation of 3,5-cyclic monophosphate (cAMP) levels can
      inhibit the VEGF-induced acute hyperpermeability, we employed multiphoton
      microscopy to quantify the cerebral microvessel permeability P to various-sized
      solutes under VEGF and cAMP treatments. The cerebral microcirculation was
      observed through a section of frontoparietal bone thinned with a microgrinder.
      Fluorescein (MW 376Da), fluorescein isothioyanate-dextran-20k (FITC-Dex-20k),
      FITC-Dex-70k, or Alexa Fluor 488-IgG in 1% bovine serum albumin mammalian
      Ringer's solution was injected into the cerebral circulation via the ipsilateral
      carotid artery with a syringe pump. Simultaneously, temporal images were
      collected from the brain parenchyma ~100-200 MUm below the pia mater. P was
      determined from the rate of tissue solute accumulation around individual
      microvessels. Exposure to 1 nM VEGF transiently increased P to 2.2, 10.5, 9.8,
      and 12.8 times control values, for fluorescein, Dex-20k, Dex-70k, and IgG,
      respectively, within 30 sec, and all returned to control levels within 2 min.
      After 20 min of pretreatment with 2 mM of the cAMP analog 8-bromo-cAMP, the
      initial increase by 1 nM VEGF was completely abolished in P of all solutes. The
      response pattern of P to VEGF and cAMP and the ratios of the peak to control
      values for rat cerebral microvessels are similar to those for rat mesenteric
      (peripheral) microvessels, except that the ratios are higher in P of cerebral
      microvessels for the intermediate and large solutes. These results imply a new
      approach for delivering large therapeutic agents to the brain.

PMID- 25066134
TI  - Nucleotide exchange in dimeric MCAK induces longitudinal and lateral stress at
      microtubule ends to support depolymerization.
AB  - Members of the kinesin-13 subfamily use motor domains in an unconventional
      fashion to initiate microtubule (MT) depolymerization at MT ends, suggesting
      unique conformational transitions for lattice engagement, end adaptation, or
      both. Using hydrogen-deuterium exchange and electron microscopy, we explored
      conformational changes in free dimeric mitotic centromere-associated kinesin
      (MCAK) and when bound to a depolymerization intermediate. ATP hydrolysis relaxes
      the conformation of the dimer, notably in the neck and N-terminal domain.
      Exchanging ADP in dimeric MCAK with ATP at the MT plus end induces outward
      curvature in alpha/beta-tubulin, accompanied by a restructuring of the MCAK neck
      and N terminus, as it returns to a closed state. Reestablishing a closed dimer
      induces lateral separation of paired tubulin dimers, which may assist in
      depolymerization. Thus, full-length ADP-MCAK transitions from an open diffusion
      competent configuration to a closed state upon plus end-mediated nucleotide
      exchange, which is mediated by conformational changes in the N-terminal domains
      of the dimer. 

PMID- 25066135
TI  - Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new
      challenges.
AB  - Despite tremendous successes of GPCR crystallography, the receptors with
      available structures represent only a small fraction of human GPCRs. An important
      role of the modeling community is to maximize structural insights for the
      remaining receptors and complexes. The community-wide GPCR Dock assessment was
      established to stimulate and monitor the progress in molecular modeling and
      ligand docking for GPCRs. The four targets in the present third assessment round
      presented new and diverse challenges for modelers, including prediction of
      allosteric ligand interaction and activation states in 5-hydroxytryptamine
      receptors 1B and 2B, and modeling by extremely distant homology for smoothened
      receptor. Forty-four modeling groups participated in the assessment. State-of-the
      art modeling approaches achieved close-to-experimental accuracy for small rigid
      orthosteric ligands and models built by close homology, and they correctly
      predicted protein fold for distant homology targets. Predictions of long loops
      and GPCR activation states remain unsolved problems. 

PMID- 25066136
TI  - Crystal structure of the E. coli peptide transporter YbgH.
AB  - E. coli YbgH belongs to the family of proton-dependent oligopeptide transporters
      (POTs), a subfamily of the major facilitator superfamily (MFS) of secondary
      active transporters. Like other MFS transporters, POT proteins switch between two
      major conformations during substrate transport. Apart from possessing a canonical
      12-helix, two-domain transmembrane (TM) core, prokaryotic POT proteins usually
      have two TM helices inserted between the two domains. Here we determined the
      crystal structure of YbgH in its inward-facing conformation. Our structure-based
      functional studies investigated the roles of both the POT signature motif 2 and
      the inserted interdomain TM helix pair in the stabilization and regulation of the
      major conformational change in MFS/POT transporters. Furthermore, of all the
      proton-titratable amino acid residues, Glu21 is the only conserved one (among
      POTs) located in the central cavity and is critical for in vivo transport.
      Together, our results support the notion that MFS symporters utilize a transport
      mechanism based on substrate-protonation coupling. 

PMID- 25066138
TI  - An H1-H3 chimeric influenza virosome confers complete protection against lethal
      challenge with PR8 (H1N1) and X47 (H3N2) viruses in mice.
AB  - Annual health threats and economic damages caused by influenza virus are still a
      main concern of the World Health Organization and other health departments all
      over the world. An influenza virosome is a highly efficient immunomodulating
      carrier mimicking the natural antigen presentation pathway and has shown an
      excellent tolerability profile due to its biocompatibility and purity. The major
      purpose of this study was to construct a new chimeric virosome influenza vaccine
      containing hemagglutinin (HA) and neuraminidase (NA) proteins derived from the
      A/PR/8/1934 (H1N1) (PR8) and A/X/47 (H3N2) (X47) viruses, and to evaluate its
      efficacy as a vaccine candidate in mice. A single intramuscular vaccination with
      the chimeric virosomes provided complete protection against lethal challenge with
      the PR8 and X47 viruses. The chimeric virosomes induced high IgG antibody
      responses as well as hemagglutination inhibition (HAI) titers. HAI titers
      following the chimeric virosome vaccination were at the same level as the whole
      inactivated influenza vaccine. Mice immunized with the chimeric virosomes
      displayed considerably less weight loss and exhibited significantly reduced viral
      load in their lungs compared with the controls. The chimeric virosomes can be
      used as an innovative vaccine formulation to confer protection against a broad
      range of influenza viruses. 

PMID- 25066137
TI  - Structural basis for AMPK activation: natural and synthetic ligands regulate
      kinase activity from opposite poles by different molecular mechanisms.
AB  - AMP-activated protein kinase (AMPK) is a principal metabolic regulator affecting
      growth and response to cellular stress. Comprised of catalytic and regulatory
      subunits, each present in multiple forms, AMPK is best described as a family of
      related enzymes. In recent years, AMPK has emerged as a desirable target for
      modulation of numerous diseases, yet clinical therapies remain elusive.
      Challenges result, in part, from an incomplete understanding of the structure and
      function of full-length heterotrimeric complexes. In this work, we provide the
      full-length structure of the widely expressed alpha1beta1gamma1 isoform of
      mammalian AMPK, along with detailed kinetic and biophysical characterization. We
      characterize binding of the broadly studied synthetic activator A769662 and its
      analogs. Our studies follow on the heels of the recent disclosure of the
      alpha2beta1gamma1 structure and provide insight into the distinct molecular
      mechanisms of AMPK regulation by AMP and A769662. 

PMID- 25066139
TI  - Atypical central auditory speech-sound discrimination in children who stutter as
      indexed by the mismatch negativity.
AB  - PURPOSE: Recent theoretical conceptualizations suggest that disfluencies in
      stuttering may arise from several factors, one of them being atypical auditory
      processing. The main purpose of the present study was to investigate whether
      speech sound encoding and central auditory discrimination, are affected in
      children who stutter (CWS). METHODS: Participants were 10 CWS, and 12 typically
      developing children with fluent speech (TDC). Event-related potentials (ERPs) for
      syllables and syllable changes [consonant, vowel, vowel-duration, frequency (F0),
      and intensity changes], critical in speech perception and language development of
      CWS were compared to those of TDC. RESULTS: There were no significant group
      differences in the amplitudes or latencies of the P1 or N2 responses elicited by
      the standard stimuli. However, the Mismatch Negativity (MMN) amplitude was
      significantly smaller in CWS than in TDC. For TDC all deviants of the linguistic
      multifeature paradigm elicited significant MMN amplitudes, comparable with the
      results found earlier with the same paradigm in 6-year-old children. In contrast,
      only the duration change elicited a significant MMN in CWS. CONCLUSIONS: The
      results showed that central auditory speech-sound processing was typical at the
      level of sound encoding in CWS. In contrast, central speech-sound discrimination,
      as indexed by the MMN for multiple sound features (both phonetic and prosodic),
      was atypical in the group of CWS. Findings were linked to existing
      conceptualizations on stuttering etiology. EDUCATIONAL OBJECTIVES: The reader
      will be able (a) to describe recent findings on central auditory speech-sound
      processing in individuals who stutter, (b) to describe the measurement of
      auditory reception and central auditory speech-sound discrimination, (c) to
      describe the findings of central auditory speech-sound discrimination, as indexed
      by the mismatch negativity (MMN), in children who stutter.

PMID- 25066140
TI  - Intratympanic dexamethasone plus melatonin versus melatonin only in the treatment
      of unilateral acute idiopathic tinnitus.
AB  - PURPOSE: The aim of our study was to determine whether the combination of
      intratympanic (IT) corticosteroid with melatonin could be associated with
      decreased tinnitus in patients with unilateral acute idiopathic tinnitus
      developed within 3months. MATERIALS AND METHODS: We evaluated this hypothesis
      through a prospective, randomized, controlled, double-blinded trial. Patients
      included in the study were randomly allocated into two groups: Group A -
      comprising 30 patients, received melatonin and IT dexamethazone, and Group B -
      including 30 patients receiving melatonin alone. After 3 months, improvement in
      tinnitus was assessed using different outcome measures: tinnitus loudness score,
      tinnitus awareness score, Tinnitus Handicap Inventory (THI), Pittsburgh Sleep
      Quality Index (PSQI) and Beck Depression Inventory (BDI). RESULTS: We have
      demonstrated significant improvements in each of the above mentioned outcomes
      subsequent to treatment in both groups. However, patients in the IT dexamathazone
      and melatonin group attained statistically significant better outcomes. Besides,
      the differences in improvement rate and cure rate were highly significant between
      the two groups, favoring the IT dexamethazone and melatonin group. CONCLUSIONS:
      Our preliminary study demonstrated that IT dexamethazone plus melatonin is
      efficient in improvement of idiopathic unilateral tinnitus developed within 3
      months.

PMID- 25066143
TI  - Posterior reversible encephalopathy syndrome in an adult with nephrotic syndrome.

PMID- 25066142
TI  - Vancomycin dosing nomogram for haemodialysis patients.

PMID- 25066141
TI  - The effects of co-morbidity in defining major depression subtypes associated with
      long-term course and severity.
AB  - BACKGROUND: Although variation in the long-term course of major depressive
      disorder (MDD) is not strongly predicted by existing symptom subtype
      distinctions, recent research suggests that prediction can be improved by using
      machine learning methods. However, it is not known whether these distinctions can
      be refined by added information about co-morbid conditions. The current report
      presents results on this question. METHOD: Data came from 8261 respondents with
      lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health
      (WMH) Surveys. Outcomes included four retrospectively reported measures of
      persistence/severity of course (years in episode; years in chronic episodes;
      hospitalization for MDD; disability due to MDD). Machine learning methods
      (regression tree analysis; lasso, ridge and elastic net penalized regression)
      followed by k-means cluster analysis were used to augment previously detected
      subtypes with information about prior co-morbidity to predict these outcomes.
      RESULTS: Predicted values were strongly correlated across outcomes. Cluster
      analysis of predicted values found three clusters with consistently high,
      intermediate or low values. The high-risk cluster (32.4% of cases) accounted for
      56.6-72.9% of high persistence, high chronicity, hospitalization and disability.
      This high-risk cluster had both higher sensitivity and likelihood ratio positive
      (LR+; relative proportions of cases in the high-risk cluster versus other
      clusters having the adverse outcomes) than in a parallel analysis that excluded
      measures of co-morbidity as predictors. CONCLUSIONS: Although the results using
      the retrospective data reported here suggest that useful MDD subtyping
      distinctions can be made with machine learning and clustering across multiple
      indicators of illness persistence/severity, replication with prospective data is
      needed to confirm this preliminary conclusion.

PMID- 25066144
TI  - Acquired reactive perforating dermatosis: a rare skin manifestation in end stage
      renal disease.

PMID- 25066145
TI  - Making primary care people-centred: a 21st century blueprint.

PMID- 25066146
TI  - STOP TB--moving out and moving on.

PMID- 25066147
TI  - The real meaning of US hospital rankings.

PMID- 25066148
TI  - More multiarm randomised trials of superiority are needed.

PMID- 25066149
TI  - The Wakley Essay Prize 2014: the best of both worlds.

PMID- 25066151
TI  - Rana Dajani: stem-cell research and ethics in the Middle East.

PMID- 25066152
TI  - International comparisons of acute myocardial infarction.

PMID- 25066153
TI  - International comparisons of acute myocardial infarction.

PMID- 25066154
TI  - International comparisons of acute myocardial infarction.

PMID- 25066155
TI  - International comparisons of acute myocardial infarction - Authors'reply.

PMID- 25066156
TI  - International comparisons of acute myocardial infarction.

PMID- 25066157
TI  - Medical education leaders' perceptions of postgraduate medical education reform.

PMID- 25066158
TI  - Time for universal provision of take-home naloxone.

PMID- 25066159
TI  - Fever, night sweats, and abnormal liver enzymes.

PMID- 25066160
TI  - Commentary on: Laparoscopic sleeve gastrectomy in patients over 60 years: impact
      of age on weight loss and co-morbidity improvement.

PMID- 25066161
TI  - Comment on: Comparison of laparoscopic sleeve gastrectomy leak rates in 4 staple
      line reinforcement options: a systematic review.

PMID- 25066162
TI  - Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of
      nascent hair follicles but is not required for follicle formation.
AB  - Hair follicle (HF) morphogenesis relies on the coordinated exchange of signals
      between mesenchymal and epithelial compartments of embryonic skin. Chemokine
      receptor Cxcr4 expression was recently identified in dermal condensates (DCs) of
      nascent HFs, but its role in promoting HF morphogenesis remains unknown. Our
      analyses confirmed Cxcr4 expression in condensate cells, and additionally
      revealed transient Cxcr4 expression in incipient epithelial hair placodes.
      Placodal Cxcr4 appeared prior to detection in DCs, representing a switch of
      expression between epithelial and mesenchymal compartments. To explore the
      functional role of this receptor in both compartments for early HF formation, we
      conditionally ablated Cxcr4 with condensate-targeting Tbx18(cre) knock-in and
      epidermis-targeting Krt14-cre transgenic mice. Conditional knockouts for both
      crosses were viable throughout embryogenesis and into adulthood. Morphological
      and biochemical marker analyses revealed comparable numbers of HFs forming in
      knockout embryos compared to wild-type littermate controls in both cases,
      suggesting that neither dermal nor epithelial Cxcr4 expression is required for
      early HF morphogenesis. We conclude that Cxcr4 expression and chemokine signaling
      through this receptor in embryonic mouse skin is dispensable for HF formation. 

PMID- 25066163
TI  - Acute unintentional intoxication with paraffin in a 25-year old patient -
      clinical case report.
AB  - "Fire-breathing" or "fire-eating" is a special kind of street art where the acts
      are always stunning, spectacular and amazing. People exhibiting this kind of show
      are professionals, not rare amateurs, who use different kind of fuels, usually
      hydrocarbons, in order to produce a pillar of fire. Intoxications caused by
      ingestion or inhalation of liquid paraffin, used as a fuel while performing, are
      numerous and various. We present a clinical case report of a 25-year old,
      previously healthy, amateur "fire-breather". During October, 2010 this young men
      arrived at the Emergency Unit of the University Clinic for toxicology and Urgent
      Internal Medicine in a severe clinical condition, after his unsuccessful attempt
      to perform real "fire-breathing". He had fever, strong headaches, mild abdominal
      and chest pain and he also had difficulties breathing and persistent dry cough.
      The patient was extremely dyspneic with peripheral cyanosis and shortness of
      breath. "Fire-breathers" must be viewed as a population at risk of paraffin
      induced pneumonia, which has low mortality rate, but still is related with
      numerous and various chronic complications. Our patient was first in a life
      threatening, extremely serious clinical condition which was urgently treated with
      appropriate vigorous and effective therapy. This therapeutic protocol led to
      successful full recovery of these young men, who luckily didn't exhibit any
      chronic complications. 

PMID- 25066164
TI  - Sudden death of a 15-year-old girl due to fulminant type 1 diabetes mellitus
      diabetic ketoacidosis induced cerebral edema?
AB  - Sudden death from fulminant type 1 diabetes mellitus is uncommon in forensic
      practice. Here we report the sudden death of a 15-year-old girl who presented
      with vomiting, fever and abdominal pain and died unexpectedly. Postmortem
      examination showed severe pancreatic islet destruction, cerebral edema and lipid
      vacuolization of the epithelium of the renal proximal tubules and liver cells.
      The biochemical analysis in reserved heart blood and vitreous fluid indicated the
      elevated levels of glucose and ketone bodies and lower glycosylated hemoglobin
      and C-peptide. The cause of death was attributed to fulminant type 1 diabetes
      mellitus which led to diabetic ketoacidosis-associated cerebral edema. This
      report suggested that the histological examination of the pancreas, liver and
      kidney, insulin immunohistochemistry, as well as biochemical analysis could be
      useful for the diagnosis of diabetes related death. 

PMID- 25066165
TI  - Patterned postmortem ant abrasions outlining clothing and body position after
      death.
AB  - Analysis of a series of cases where post mortem lesions had been caused by ant
      activity demonstrated two types of specific lesions, the first associated with
      clothing, and the second with the position of the body of the decedent. The first
      type of injury consisted of areas of abraded parchmented skin with well-defined
      straight edges that marked the perimeter of clothing. The second lesion consisted
      of circular abraded injuries that outlined the junction between the body and the
      surface that it was resting on, essentially tracing the outline of the point of
      contact. In both situations ants had been unable to gain access to skin beneath
      elasticized clothing or parts of the body pressed against the floor or ground.
      This had resulted in a visual record of the edge of clothing and the position of
      parts of the body after death. This information may be important if clothing has
      been removed prior to autopsy or if lividity is minimal. These unique lesions
      also show that not all insect predation on bodies obscures information. 

PMID- 25066166
TI  - Response to "a rose by any other name" published in the 2014 July edition of the
      Journal of Forensic and Legal Medicine.

PMID- 25066167
TI  - Injuries and absenteeism among motorcycle taxi drivers who are victims of traffic
      accidents.
AB  - Facial injuries frequently occur in traffic accidents involving motorcycles. The
      purpose of this study was to determine the prevalence of facial injuries among
      motorcycle drivers who perform motorcycle taxi service. The study design was
      cross-sectional. A total of 210 participants who served as motorcycle taxi
      drivers in a city in northeastern Brazil completed a survey concerning their
      experience of accidents involving facial injuries and consequent hospitalization
      and absenteeism from work. The motorcycle drivers included in the study were
      randomly selected from a list provided by the city. Out of the respondents, 165
      (78.6%) who were involved in traffic accidents in the last 12 months, 15 (9.1%)
      reported facial injuries. The types of facial injury most frequently reported
      involved soft tissues (n = 8; 53.3%), followed by simple fracture (n = 4; 26.7%)
      and dentoalveolar fracture (n = 3; 20%). We found an association between facial
      injuries and absenteeism, as well as an association between the presence of
      facial injury and the need for hospitalization for a period of 2 days or more.
      Respondents reported that they had accidents, but due to the use of full face
      motorcycle helmet the number of facial injuries was low. For most of them,
      absenteeism was observed for a period of one month or more. 

PMID- 25066168
TI  - Quantitative analysis of injury characteristics in victims of interpersonal
      violence: an emergency department perspective.
AB  - Violence runs into the fabric of society. In recent years, violence has been
      identified as an important health problem in industrialised societies. In the
      present study, conducted to analyze injury characteristics, 813 victims of
      interpersonal violence presenting to emergency department at a Government Medical
      College and Hospital from a major city in Central India were interviewed and
      examined over a period of one year. Central to the quantitative analysis of the
      data collected was the extraction of specific injury characteristics from the
      sample population. The group included 606 men and 207 females, most of them were
      resident of urban areas, aged between 11 and 30 years. Most of attacks occurred
      at nights, with minimal seasonal variation. Males were more commonly attacked
      outdoors by a single stranger male while females were mostly attacked indoors by
      spouse. Blunt trauma was more commonly seen in females as compared to males. Head
      neck and face region was the most preferred anatomical site by the assailants.
      Hard and blunt weapons were used more commonly at homes (184 of 269 incidents)
      than at streets (301 of 561 incidents). Sharp edged and pointed weapons were most
      commonly used at streets. Firearms were rarely used. Occurrence of physical
      assaults in this region more or less follows the pattern seen in other parts of
      the world with local and socio-cultural differences that need to be further
      delved into and considered during the planning and implementation of injury
      prevention programs. 

PMID- 25066169
TI  - Mental health and health-care use of detainees in police custody.
AB  - BACKGROUND: In many countries, forensic physicians function as primary care
      providers for detainees in police custody. Their task is comparable to the tasks
      of general practitioners. Nevertheless, problems presented by both patient
      populations may differ. We therefore aimed to systematically compare presented
      problems and medication use in a population of police detainees to those of
      regular patients in general practice. METHODS: Health problems and prescription
      medications of 3232 detainees seen by the Amsterdam Forensic Medical Service were
      compared to those of general practice patients (n = 78,975) adjusted for age and
      gender during a 12-month period. RESULTS: Among those obtaining medical attention
      (28% of all detainees), almost 50% were diagnosed with mental health problems,
      with substance abuse as the leading reason for consultation. Forty-two percent
      received at least one prescription affecting the nervous system. In general
      practice, 17% (P < 0.001) of patients consulting their GP were diagnosed with
      mental health problems and 22% (P < 0.001) were prescribed medications affecting
      the nervous system. CONCLUSION: The magnitude of mental health problems among
      police detainees has significant implications for the qualifications of police
      health staff and those who provide health care in the police setting especially
      concerning substance abuse.

PMID- 25066170
TI  - Analysis of the procedures used to evaluate suicide crime scenes in Brazil: a
      statistical approach to interpret reports.
AB  - This study uses statistical techniques to evaluate reports on suicide scenes; it
      utilizes 80 reports from different locations in Brazil, randomly collected from
      both federal and state jurisdictions. We aimed to assess a heterogeneous group of
      cases in order to obtain an overall perspective of the problem. We evaluated
      variables regarding the characteristics of the crime scene, such as the detected
      traces (blood, instruments and clothes) that were found and we addressed the
      methodology employed by the experts. A qualitative approach using basic
      statistics revealed a wide distribution as to how the issue was addressed in the
      documents. We examined a quantitative approach involving an empirical equation
      and we used multivariate procedures to validate the quantitative methodology
      proposed for this empirical equation. The methodology successfully identified the
      main differences in the information presented in the reports, showing that there
      is no standardized method of analyzing evidences. 

PMID- 25066171
TI  - Fatal injuries among motorcyclists in Klang Valley, Malaysia.
AB  - BACKGROUND: Motorcycle fatalities constitute the majority of road traffic deaths
      in Malaysia. The aims of this study were to describe the pattern of fatal
      injuries among Klang Valley fatal motorcyclists and to describe the factors
      associated with fatal (vs non-fatal) injuries. METHODS: A cross-sectional
      analysis was performed on data from a case series of injured (fatal and non
      fatal) motorcyclists recruited from Klang Valley between 14th March 2010 and 13th
      March 2011. Fatal cases in the cases series were identified from the Police
      files. Non-fatal cases were recruited from five major hospitals in the study
      region. Information used in the analyses were obtained from Police crash reports,
      hospital medical records, and Coroner's records of the participant sample.
      RESULTS: Of the 177 fatal cases, 142 (80.2%) were categorised as instantaneous
      death while 35 (19.8%) cases were categorised as experiencing delayed death.
      Thirty two percent of the cases had a Maximum Abbreviated Injury Score (MAIS) of
      5 with head injury being the most common cause of death. Significant predictors
      of fatal (vs non-fatal) injury included ethnic groups, monthly income, alcohol
      and drug use and road type. Alcohol and drug use was shown to be the strongest
      predictor with adjusted odds ratio (AOR) of 14.77 (95% CI 3.32-65.65).
      CONCLUSION: Factors related to the motorcyclists, road user behaviour and the
      road environment as well as pre-hospitalisation emergency care must be addressed
      efficiently in low and middle income countries to reduce the number and severity
      of motorcycle-related injuries.

PMID- 25066172
TI  - When nightclub security agents assault clients more insight through a qualitative
      approach.
AB  - Between 2007 and 2009, aggressions by security agents of nightclubs on clients
      increased from 6% to 10% among community violence situations encountered at the
      Violence Medical Unit (VMU) at the Lausanne University Hospital in Switzerland.
      Most victims were young men who had been drinking alcohol before the assault.
      About one quarter (25.7%) presented with one or several fractures, all of them in
      the head area. (For more details, refer to the previous article "When nightclub
      security agents assault clients" published in 2012(1).) Following this first
      study, we performed a second qualitative study in order to bring more information
      about the context and highlight victims' behaviors and experiences. Four themes
      emerged: how the assault began; the assault itself; third-party involvement; and
      the psychological state of victims when they consulted the VMU. The findings of
      this second study complemented the statistical results of the first study by
      showing under what circumstances security agents of nightclubs respond with
      physical violence to situations they consider a threat to security. Furthermore,
      the study described consequences for the victims that could be quite serious. Our
      findings support the need for nightclubs to improve selection and training of
      security staff. 

PMID- 25066173
TI  - Use of kangri (a traditional firepot) as a weapon.
AB  - Kangri an earthenware firepot has been traditionally used by people of Kashmir
      for protecting themselves for harsh winter weather. This study done on patients
      admitted in the burns ward and general emergency ward of a tertiary care
      hospital, is perhaps the first of its kind. It analyses the use of this very
      traditional and useful art form as a weapon that can cause significant damage
      during interpersonal conflicts. As is clear from the study its use as weapon can
      inflict considerable damage and can lead to lifelong disabilities. Out of the 20
      cases studied over a period of one year 2 cases received grievous injuries over
      head and face region in form of permanent disfigurement. Almost half of the
      injuries i.e. 7 cases were mechanical in nature whereas rest 13 cases belong to
      thermal category. Most of the injuries were simple and healed with preliminary
      medical attention but in 2 cases there was permanent disfigurement and both were
      because of deep burns. 

PMID- 25066174
TI  - Causes of unnatural deaths among children and adolescents in northern India - a
      qualitative analysis of postmortem data.
AB  - Aim of the study was to ascertain the various causes of unnatural deaths among 1
      19 years analysing the postmortem data in a regional referral centre of northern
      India. A retrospective observational study from the data base was done for the
      same. All unnatural deaths in children aged 1-19 years from April 2010 to March
      2011 were identified from the postmortem database. The children were classified
      into 3 groups-1-5 years, 6-10 years and 11-19 years separately for males and
      females. The various modes of unnatural deaths were identified and analysed.
      Retrospective analysis of Postmortem data during one year revealed total of 434
      unnatural deaths in children aged 1-19 years. The most vulnerable age group
      included children between 11-19 years (74.5%). Females (51.6%) marginaly
      outnumbered the males (48.4%). Flame Burns (58.3%) was the commonest cause of
      death in all age followed by road traffic accidents 15%, electrocution 7.8% &
      Poisoning accounted for 6%. The most frequent victims were adolescents (74%)
      almost 3 times that of other age group. This study showed Adolescents were the
      most common victims of the unnatural death with flame burn being the most common
      cause followed by RTA, electrocution and poisoning. 

PMID- 25066175
TI  - The Weighted Average Method 'WAM' for dental age estimation: a simpler method for
      children at the 10 year threshold: "it is vain to do with more when less will
      suffice" William of Ockham 1288-1358.".
AB  - The mathematical principle of weighting averages to determine the most
      appropriate numerical outcome is well established in economic and social studies.
      It has seen little application in forensic dentistry. This study re-evaluated the
      data from a previous study of age assessment at the 10 year threshold. A
      semiautomatic process of weighting averages by n-td, x-tds, sd-tds, se-tds, 1/sd
      tds, 1/se-tds was prepared in an Excel worksheet and the different weighted mean
      values reported. In addition the Fixed Effects and Random Effects models for Meta
      Analysis were used and applied to the same data sets. In conclusion it has been
      shown that the most accurate age estimation method is to use the Random Effects
      Model for the mathematical procedures. 

PMID- 25066176
TI  - Dental age estimation: the role of probability estimates at the 10 year
      threshold.
AB  - INTRODUCTION: The use of probability at the 18 year threshold has simplified the
      reporting of dental age estimates for emerging adults. The availability of simple
      to use widely available software has enabled the development of the probability
      threshold for individual teeth in growing children. MATERIALS AND METHODS: Tooth
      development stage data from a previous study at the 10 year threshold were reused
      to estimate the probability of developing teeth being above or below the 10 year
      thresh-hold using the NORMDIST Function in Microsoft Excel. The probabilities
      within an individual subject are averaged to give a single probability that a
      subject is above or below 10 years old. To test the validity of this approach
      dental panoramic radiographs of 50 female and 50 male children within 2 years of
      the chronological age were assessed with the chronological age masked. Once the
      whole validation set of 100 radiographs had been assessed the masking was removed
      and the chronological age and dental age compared. The dental age was compared
      with chronological age to determine whether the dental age correctly or
      incorrectly identified a validation subject as above or below the 10 year
      threshold. RESULTS: The probability estimates correctly identified children as
      above or below on 94% of occasions. Only 2% of the validation group with a
      chronological age of less than 10 years were assigned to the over 10 year group.
      CONCLUSIONS: This study indicates the very high accuracy of assignment at the 10
      year threshold. Further work at other legally important age thresholds is needed
      to explore the value of this approach to the technique of age estimation.

PMID- 25066177
TI  - Obesity, inflammation, and the gut microbiota.
AB  - As the prevalence of obesity and associated disease continues to rise and
      concerns for the spiralling economic and social costs also escalate, innovative
      management strategies beyond primary prevention and traditional lifestyle
      interventions are urgently needed. The biological basis of disease is one avenue
      for further exploration in this context. Several key inflammatory markers have
      been consistently associated with both obesity and risk of adverse outcomes in
      obesity-associated diseases, which suggests that a persistent, low-grade,
      inflammatory response is a potentially modifiable risk factor. In this Review, we
      provide evidence supporting perturbation of the intestinal microbiota and changes
      in intestinal permeability as potential triggers of inflammation in obesity.
      Further characterisation of the mechanisms underpinning the triggers of such
      inflammatory responses in overweight and obese individuals could offer unique
      opportunities for intervention strategies to help ameliorate the risk of obesity
      associated disease. 

PMID- 25066178
TI  - Gender identity rather than sexual orientation impacts on facial preferences.
AB  - INTRODUCTION: Differences in facial preferences between heterosexual men and
      women are well documented. It is still a matter of debate, however, how
      variations in sexual identity/sexual orientation may modify the facial
      preferences. AIM: This study aims to investigate the facial preferences of male
      to-female (MtF) individuals with gender dysphoria (GD) and the influence of short
      term/long-term relationships on facial preference, in comparison with healthy
      subjects. METHODS: Eighteen untreated MtF subjects, 30 heterosexual males, 64
      heterosexual females, and 42 homosexual males from university students/staff, at
      gay events, and in Gender Clinics were shown a composite male or female face. The
      sexual dimorphism of these pictures was stressed or reduced in a continuous
      fashion through an open-source morphing program with a sequence of 21 pictures of
      the same face warped from a feminized to a masculinized shape. MAIN OUTCOME
      MEASURES: An open-source morphing program (gtkmorph) based on the X-Morph
      algorithm. RESULTS: MtF GD subjects and heterosexual females showed the same
      pattern of preferences: a clear preference for less dimorphic (more feminized)
      faces for both short- and long-term relationships. Conversely, both heterosexual
      and homosexual men selected significantly much more dimorphic faces, showing a
      preference for hyperfeminized and hypermasculinized faces, respectively.
      CONCLUSIONS: These data show that the facial preferences of MtF GD individuals
      mirror those of the sex congruent with their gender identity. Conversely,
      heterosexual males trace the facial preferences of homosexual men, indicating
      that changes in sexual orientation do not substantially affect preference for the
      most attractive faces.

PMID- 25066179
TI  - A comparison of atomistic and continuum approaches to the study of bonding
      dynamics in electrocatalysis: microcantilever stress and in situ EXAFS
      observations of platinum bond expansion due to oxygen adsorption during the
      oxygen reduction reaction.
AB  - Microcantilever stress measurements are examined to contrast and compare their
      attributes with those from in situ X-ray absorption spectroscopy to elucidate
      bonding dynamics during the oxygen reduction reaction (ORR) on a Pt catalyst. The
      present work explores multiple atomistic catalyst properties that notably include
      features of the Pt-Pt bonding and changes in bond strains that occur upon
      exposure to O2 in the electrochemical environment. The alteration of the Pt
      electronic and physical structures due to O2 exposure occurs over a wide
      potential range (1.2 to 0.4 V vs normal hydrogen electrode), a range spanning
      potentials where Pt catalyzes the ORR to those where Pt-oxide forms and all ORR
      activity ceases. We show that Pt-Pt surface bond strains due to oxygen
      interactions with Pt-Pt bonds are discernible at macroscopic scales in cantilever
      based bending measurements of Pt thin films under O2 and Ar. Complementary
      extended X-ray absorption fine structure (EXAFS) measurements of nanoscale Pt
      clusters supported on carbon provide an estimate of the magnitude and direction
      of the in-operando bond strains. The data show that under O2 the M-M bonds
      elongate as compared to an N2 atmosphere across a broad range of potentials and
      ORR rates, an interfacial bond expansion that falls within a range of 0.23 (+/
      0.15)% to 0.40 (+/-0.20)%. The EXAFS-measured Pt-Pt bond strains correspond to a
      stress thickness and magnitude that is well matched to the predictions of a
      mechanics mode applied to experimentally determined data obtained via the
      cantilever bending method. The data provide new quantitative understandings of
      bonding dynamics that will need to be considered in theoretical treatments of ORR
      catalysis and substantiate the subpicometer resolution of electrochemically
      mediated bond strains detected on the macroscale. 

PMID- 25066180
TI  - Mechanistic insights into Pin1 peptidyl-prolyl cis-trans isomerization from
      umbrella sampling simulations.
AB  - The peptidyl-proyl isomerase Pin1 plays a key role in the regulation of
      phospho(p)-Ser/Thr-Pro proteins, acting as a molecular timer of the cell cycle.
      After recognition of these motifs, Pin1 catalyzes the rapid cis-trans
      isomerization of proline amide bonds of substrates, contributing to maintain the
      equilibrium between the two conformations. Although a great interest has arisen
      on this enzyme, its catalytic mechanism has long been debated. Here, the cis
      trans isomerization of a model peptide system was investigated by means of
      umbrella sampling simulations in the Pin1-bound and unbound states. We obtained
      free energy barriers consistent with experimental data, and identified several
      enzymatic features directly linked to the acceleration of the prolyl bond
      isomerization. In particular, an enhanced autocatalysis, the stabilization of
      perturbed ground state conformations, and the substrate binding in a procatalytic
      conformation were found as main contributions to explain the lowering of the
      isomerization free energy barrier.

PMID- 25066181
TI  - Reappraising the long-term course and outcome of psychotic disorders: the AESOP
      10 study.
AB  - BACKGROUND: Studies of the long-term course and outcome of psychoses tend to
      focus on cohorts of prevalent cases. Such studies bias samples towards those with
      poor outcomes, which may distort our understanding of prognosis. Long-term follow
      up studies of epidemiologically robust first-episode samples are rare. METHOD:
      AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of
      psychosis initially identified in two areas in the UK (South East London and
      Nottingham). Detailed information was collated on course and outcome in three
      domains (clinical, social and service use) from case records, informants and
      follow-up interviews. RESULTS: At follow-up, of 532 incident cases identified, at
      baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of
      the remaining 458, 412 (90%) were traced and some information on follow-up was
      collated for 387 (85%). Most cases (265, 77%) experienced at least one period of
      sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2
      years. A majority (208, 72%) of cases had been employed for less than 25% of the
      follow-up period. The median number of hospital admissions, including at first
      presentation, was 2 [interquartile range (IQR) 1-4]; a majority (299, 88%) were
      admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall,
      outcomes were worse for those with a non-affective diagnosis, for men and for
      those from South East London. CONCLUSIONS: Sustained periods of symptom remission
      are usual following first presentation to mental health services for psychosis,
      including for those with a non-affective disorder; almost half recover.

PMID- 25066182
TI  - Fructose malabsorption is not uncommon among patients with irritable bowel
      syndrome in India: a case-control study.
AB  - BACKGROUND: Fructose malabsorption (FM) is reported in 38 % to 75 % patients with
      irritable bowel syndrome (IBS). Most of these studies, however, had limitations
      due to use of variable dose of fructose, small sample size, and lack of control
      population. Moreover, there is no study on this issue from India. Hence, in this
      prospective study, we evaluated the frequency of FM on an adequately powered
      sample of patients with IBS and healthy controls (HC) from India. METHODS: Ninety
      seven patients with IBS (diagnosed using Rome III criteria) and 41 healthy
      controls were evaluated for FM by fructose hydrogen breath test (FHBT) using 25 g
      fructose. Persistent rise (at least two readings) in breath hydrogen 20 parts per
      million (PPM) above basal was considered diagnostic of FM. RESULTS: Patients and
      controls were comparable in age (37 years [21-66] vs. 33 years [15-56]; p = 0.1)
      and gender (76/97 [78.4 %] vs. 29/41 [70.7 %] male; p = 0.3). Of 70 patients
      reporting data on Bristol's stool forms, 10 (14 %), 43 (61 %), and 17 (25 %) had
      constipation, diarrhea predominant and unclassified IBS (Asian classification),
      respectively. Patients with IBS more often had FM than controls on FHBT (14/97
      [14.4 %] vs. 1/41 [2.4 %]; p = 0.04). Patients with FM more often had diarrhea
      predominant IBS than those without FM (10/11 [91 %] vs. 33/59 [56 %]; p = 0.02).
      CONCLUSION: Though FM was not very common among Indian patients with IBS, it was
      higher among them than controls. Patients with FM more often had diarrhea
      predominant IBS.

PMID- 25066183
TI  - Preventing the dissolution of lithium polysulfides in lithium-sulfur cells by
      using Nafion-coated cathodes.
AB  - The principal drawback of lithium-sulfur batteries is the dissolution of long
      chain lithium polysulfides into the electrolyte, which limits cycling
      performance. To overcome this problem, we focused on the development of a novel
      cathode as well as anode material and designed Nafion-coated NiCrAl/S as a
      cathode and lithium powder as an anode. Nafion-coated NiCrAl/S cathode was
      synthesized using a two-step dip-coating technique. The lithium-powder anode was
      used instead of a lithium-foil anode to prohibit dendrite growth and to improve
      on the electrochemical behaviors. The cells showed an initial discharge capacity
      of about 900 mA g(-1) and a final discharge capacity of 772 mA g(-1) after 100
      cycles at 0.1 C-rate. Scanning electron microscopy (SEM) and X-ray photoelectron
      spectroscopy (XPS) demonstrate that using the Nafion-coated NiCrAl/S cathode can
      suppress the dissolution of long-chain lithium polysulfides. 

PMID- 25066184
TI  - Alpha-1 antitrypsin and liver disease: mechanisms of injury and novel
      interventions.
AB  - alpha-1-Antitrypsin (alpha1AT) is a serum glycoprotein synthesized in the liver.
      The majority of patients with alpha1AT deficiency liver disease are homozygous
      for the Z mutant of alpha1AT (called ZZ or 'PIZZ'). This mutant gene directs the
      synthesis of an abnormal protein which folds improperly during biogenesis. Most
      of these mutant Z protein molecules undergo proteolysis; however, some of the
      mutant protein accumulates in hepatocytes. Hepatocytes with the largest mutant
      protein burdens undergo apoptosis, causing compensatory hepatic proliferation.
      Cycles of hepatocyte injury, cell death and compensatory proliferation results in
      liver disease ranging from mild asymptomatic enzyme elevations to hepatic
      fibrosis, cirrhosis and hepatocellular carcinoma. There is a high variability in
      clinical disease presentation suggesting that environmental and genetic modifiers
      are important. Management of alpha1AT liver disease is based on standard
      supportive care and liver transplant. However, increased understanding of the
      cellular mechanisms of liver injury has led to new clinical trials. 

PMID- 25066185
TI  - Region of birth, sex, and reproductive health in rural immigrant latino
      farmworkers: the MICASA study.
AB  - PURPOSE: Characterize sexual and reproductive health among immigrant Latino
      farmworkers. METHODS: We surveyed 806 immigrant Latino farmworkers from Mexico
      and Central America in a rural agricultural community in California's Central
      Valley. FINDINGS: A total of 556 respondents were born in Mexico (272 men, 284
      women) and 250 in Central America (135 men, 115 women). The majority entered the
      United States as young adults, with median age at immigration ranging from 20
      (Mexican-born men) to 24 (Central American-born women). Nearly 95% of respondents
      were married or cohabiting. Median age for sexual debut was 18 for women and was
      younger for men (adjusted mean difference: -2.1 years, 95% CI: -2.6 to -1.7).
      Median number of lifetime sexual partners was 1 for women and greater for men
      (adjusted mean difference: 2.0 partners, 95% CI: 1.3-2.7). Contraception use was
      less likely among men and among Central American women compared to Mexico-born
      women. Among sexually active persons not using contraception, the most common
      reasons for nonuse were "Don't want to"/"Don't like any" followed by desire to
      become or being pregnant. Women reported a median of 3 pregnancies; there were no
      significant differences based on respondents' region of birth. CONCLUSIONS: This
      group of Latino immigrants demonstrated behaviors conducive to reproductive
      health: late sexual debut, few lifetime sexual partners, and high prevalence of
      marriage. Preventive education campaigns should focus on maintaining healthy
      behaviors, especially in men. Identifying groups with common provenance and
      cultural heritage may aid in maximizing acceptability and effectiveness of
      prevention programs.

PMID- 25066186
TI  - Identification of a recurrent BRCA1 exon 21-22 genomic rearrangement in Malay
      breast cancer patients.

PMID- 25066187
TI  - Attitudes of patients and care providers to enhanced recovery after surgery
      programs after major abdominal surgery.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) is a well-established pathway
      of perioperative care in surgery in an increasing number of specialties. To
      implement protocols and maintain high levels of compliance, continued support
      from care providers and patients is vital. This survey aimed to assess the
      perceptions of care providers and patients of the relevance and importance of the
      ERAS targets and strategies. MATERIALS AND METHODS: Pre- and post-operative
      surveys were completed by patients who underwent major hepatic, colorectal, or
      oesophagogastric surgery in three major centers in Scotland, Norway, and The
      Netherlands. Anonymous web-based and article surveys were also sent to surgeons,
      anesthetists, and nurses experienced in delivering enhanced recovery protocols.
      Each questionnaire asked the responder to rate a selection of enhanced recovery
      targets and strategies in terms of perceived importance. RESULTS: One hundred
      nine patients and 57 care providers completed the preoperative survey. Overall,
      both patients and care providers rated the majority of items as important and
      supported ERAS principles. Freedom from nausea (median, 10; interquartile range
      [IQR], 8-10) and pain at rest (median, 10; IQR, 8-10) were the care components
      rated the highest by both patients and care providers. Early return of bowel
      function (median, 7; IQR, 5-8) and avoiding preanesthetic sedation (median, 6;
      IQR, 3.75-8) were scored the lowest by care providers. CONCLUSIONS: ERAS
      principles are supported by both patients and care providers. This is important
      when attempting to implement and maintain an ERAS program. Controversies still
      remain regarding the relative importance of individual ERAS components.

PMID- 25066188
TI  - Falls from ladders: age matters more than height.
AB  - BACKGROUND: Falls from ladders account for a significant number of hospital
      visits. However, the epidemiology, injury pattern, and how age affects such falls
      are poorly described in the literature. MATERIALS AND METHODS: Patients >=18 y
      who suffered falls from ladders over a 51/2-y period were identified in our
      trauma registry. Dividing patients into three age groups (18-45, 46-65, and >66
      y), we compared demographic characteristics, clinical data, and outcomes
      including injury pattern and mortality. The odds ratios (ORs) were calculated
      with the group 18-45 y as reference; group means were compared with one-way
      analysis of variance. RESULTS: Of 27,155 trauma patients, 340 (1.3%) had suffered
      falls from ladders. The average age was 55 y, with a male predominance of 89.3%.
      Average fall height was 9.8 ft, and mean Injury Severity Score was 10.6.
      Increasing age was associated with a decrease in the mean fall height (P <
      0.001), an increase in the mean Injury Severity Score (P < 0.05), and higher
      likelihood of admission (>66 y: OR, 5.3; confidence interval [CI], 2.5-11.5). In
      univariate analysis, patients in the >66-y age group were more likely to sustain
      traumatic brain injuries (OR, 3.4; CI, 1.5-7.8) and truncal injuries (OR, 3.6;
      CI, 1.9-7.0) and less likely to sustain hand and/or forearm fractures (OR, 0.3;
      CI, 0.1-0.9). CONCLUSIONS: Older people are particularly vulnerable after falling
      from ladders. Although they fell from lower heights, the elderly sustained
      different and more severe injury patterns. Ladder safety education should be
      particularly tailored at the elderly.

PMID- 25066189
TI  - Organic removal assessment at full-scale treatment facilities using advanced
      organic characterization tools.
AB  - The character of dissolved organic matter (DOM) in source water determines its
      treatability in drinking water treatment. In order to understand and improve
      drinking water treatment process operations, advanced characterization tools,
      three-dimensional excitation emission matrix technology (3D-EEM) and high
      performance size exclusion chromatography (HPSEC), have been used. The DOM
      characteristics in both source and treated waters from 52 full-scale drinking
      water treatment plants of 23 cities in China were investigated. The dissolved
      organic carbon (DOC) concentration was similar as compared with other countries;
      however, differences in the compositions of DOM between Chinese water sources and
      those of other countries were observed. The assessment confirmed that the origin
      of DOM is the key factor influencing its removal. Source water with the lowest
      anthropogenic source had the best DOC removal. According to the principal
      component analysis result of DOM characteristics, the source waters were found to
      be divided into two groups based on geographic location. Source waters in the
      east, north and center of China where there are larger populations tend to
      cluster together; while those of the southwest, northwest and south of China tend
      to cluster together. These densely populated areas in China should face a bigger
      challenge of DOC removal during drinking water treatment. Moreover, it was
      concluded that more attention should be paid to advanced coagulation or hybrid
      treatment in the actual water treatment train because of the significant increase
      of the middle molecular weight fraction (1000-2000 Da) after coagulation
      treatment. 

PMID- 25066190
TI  - Overcoming confinement limited swelling in hydrogel thin films using
      supramolecular interactions.
AB  - The thin film behavior of poly(N-isopropylacrylamide-stat-2-(N
      ethylperfluorooctane sulfonamido)ethyl acrylate) (NIPAAm-stat-FOSA) based
      hydrogels containing 5 mol% FOSA was elucidated using quartz crystal microbalance
      with dissipation (QCM-D) in combination with spectroscopic ellipsometry (SE)
      through examination of the lower critical solution temperature (LCST) and
      temperature dependent swelling for (dry) thicknesses ranging from 10 nm to 121
      nm. For all thin films measured, the LCST was shown to slightly increase (>3 
      degrees C) in comparison to that of the bulk sample. However for these films, the
      increase in LCST was statistically identical, irrespective of thickness.
      Surprisingly, the volumetric swelling of the hydrogel in thin films, even at
      temperatures less than the LCST, was similar (within 20%) to the volumetric
      swelling of the bulk hydrogel, despite the expected significant decrease
      associated with the hydrogel being constrained by the substrate as predicted by
      one dimensional Flory-Rehner theory. We attribute this enhancement in swelling
      compared to theoretical expectations to the ability of the hydrophobic crosslinks
      to re-arrange under stress, which provides a mechanism to alleviate the decreased
      dimensionality imposed by the substrate; this mechanism is consistent with a
      large hysteresis in the swelling when cycling between 35  degrees C and 5 
      degrees C. Unlike the LCST, the swelling ratio increases with decreasing film
      thickness. At low temperatures (below the LCST), the volume swelling ratio
      increased from 3.9 to 4.9, while at temperatures above the LCST the swelling
      ratio increased from 1.5 to 2.5 when the film thickness decreased from 121 nm to
      10 nm. The combination of facile processing through solution casting without the
      need for additional crosslinking chemistry and limited thickness dependent
      variation of swelling and LCST behavior in these physically crosslinked hydrogels
      makes these materials attractive for applications requiring thermoresponsive soft
      coatings. 

PMID- 25066195
TI  - John Auty: (1926-2013).

PMID- 25066192
TI  - Endothelial NADPH oxidases: which NOX to target in vascular disease?
AB  - NADPH oxidases (NOXs) are reactive oxygen species (ROS)-generating enzymes
      implicated in the pathophysiology of vascular diseases such as hypertension and
      stroke. Endothelial cells express four NOX isoforms including the superoxide
      generating enzymes NOX1, NOX2, and NOX5 and the hydrogen peroxide-generating
      enzyme NOX4. Studies on arteries from patients with coronary artery disease, and
      in animals with experimentally induced hypertension, diabetes, or
      atherosclerosis, suggest that NOX1, NOX2, and NOX5 promote endothelial
      dysfunction, inflammation, and apoptosis in the vessel wall, whereas NOX4 is by
      contrast vasoprotective in increasing nitric oxide bioavailability and
      suppressing cell death pathways. Based on these findings and promising
      preclinical studies with the NOX1/NOX2 antagonist, apocynin, we suggest that the
      field is poised for clinical evaluation of NOX inhibitors as therapeutics for
      cardiovascular disease. 

PMID- 25066196
TI  - Echinococcus granulosus and other intestinal helminths: current status of
      prevalence and management in rural dogs of eastern Australia.
AB  - OBJECTIVES: Ascertain the prevalence of intestinal helminths in rural dogs from
      eastern Australia and Tasmania. Identify farm management practices contributing
      to the perpetuation and transmission of Echinococcus granulosus. METHODS:
      Helminth infection in dogs was determined microscopically through faecal
      flotation. Infection with E. granulosus was determined via faecal antigen-capture
      ELISA and coproPCR. Taeniid eggs were identified using molecular methods. Data on
      dog management and owner understanding of hydatid disease were collected via
      questionnaire. RESULTS: Faeces were collected from 1425 Australian rural dogs
      (1119 mainland; 306 Tasmania). Eggs of hookworms were most prevalent, up to
      40.2%, followed by whipworms (Trichuris vulpis), up to 21.2%. Roundworms
      (Toxocara canis and Toxascaris leonine) were least common, up to 6.1%. Taeniid
      eggs were found in 11 dogs (5 Taenia pisiformis; 2 T. serialis; 4 T. hydatigena);
      2 of the T. hydatigena-infected dogs were also E. granulosus coproantigen
      positive. Of the 45 dogs found to be E. granulosus coproantigen-positive, 24 were
      in Tasmania, 16 in NSW, 3 in Victoria and 2 in Queensland. Three Tasmanian
      coproantigen ELISA-positive dogs were also coproPCR-positive. The most common dog
      ration was commercial dry food, but half the owners fed raw meat to their dogs
      and some fed offal of lambs (8.9%) or mutton (7.8%). More than half (69%) of
      owners weighed their dogs before deworming. Few dewormed their dogs often enough
      to ensure they remained cestode-free and owners hunting wildlife usually left
      carcases where they were shot. CONCLUSIONS: E. granulosus is still present in
      Australian rural dogs, including Tasmania, but at low levels. Owner behaviour
      perpetuates transmission of cestodes.

PMID- 25066197
TI  - Trevor John Bagust: 1944-2014.

PMID- 25066191
TI  - Nuclear receptor Rev-erbalpha: up, down, and all around.
AB  - Rev-erbalpha is a nuclear receptor that links circadian rhythms to
      transcriptional control of metabolic pathways. Rev-erbalpha is a potent
      transcriptional repressor and plays an important role in the core mammalian
      molecular clock while also serving as a key regulator of clock output in
      metabolic tissues including liver and brown adipose tissue (BAT). Recent findings
      have shed new light on the role of Rev-erbalpha and its paralog Rev-erbbeta in
      rhythm generation, as well as additional regulatory roles for Rev-erbalpha in
      other tissues that contribute to energy expenditure, inflammation, and behavior.
      This review highlights physiological functions of Rev-erbalpha and beta in
      multiple tissues and discusses the therapeutic potential and challenges of
      targeting these pathways in human disease. 

PMID- 25066198
TI  - Where do Aussie vets find their antimicrobial prescribing information?

PMID- 25066199
TI  - Consent for blood transfusion: do patients understand the risks and benefits?
AB  - BACKGROUND AND OBJECTIVES: Blood transfusion is a frequent medical intervention
      in hospitals. The benefits of, risks of and alternatives to blood transfusions
      are not consistently understood by patients. The objective of this study was to
      assess gaps in knowledge and comfort with the current process of consenting
      patients for blood transfusions. A standardised video regarding the risk and
      benefits of blood transfusions was developed and feedback regarding this tool was
      assessed. METHODS: After informed consent had been obtained, 25 patients
      receiving their first transfusion at a single academic centre were asked to
      complete a survey, watch a standardised educational video and complete a follow
      up survey. RESULTS: The patient survey revealed that the information recollected
      from informed consent discussions was variable and incomplete. After the informed
      consent discussion, the majority of patients were comfortable with having a blood
      transfusion, although one-third did express concerns or worry about having a
      blood transfusion. After viewing the video, patients felt that the video improved
      their understanding of the risks (7.3 of 10), benefits (6.9 of 10) and
      alternatives (7.1 of 10) to transfusion, but it did not change their comfort with
      blood transfusion consent. CONCLUSION: Patients experienced a variable informed
      consent process prior to blood transfusion. Although the video improved their
      understanding of risks, it did not improve patient comfort towards giving consent
      for transfusion as the level of comfort was already high. The video is available
      online (http://www.youtube.com/watch?v=RxaPnLkgh-0) as an optional resource for
      patients (and physicians) who wish to receive standardised and accurate
      information about blood transfusions.

PMID- 25066200
TI  - Do older individuals have difficulty processing motion or excluding noise?
      Implications for safe driving.
AB  - This study aimed to determine if difficulties extracting signal from noise
      explained poorer coherent motion thresholds in older individuals, particularly
      women. In four experimental conditions the contrast of the signal and noise dots
      used in a random dot kinematogram was manipulated. Coherence thresholds were
      highest when the signal dots were of a lower contrast than the noise dots and
      lowest when the signal dots were of a higher contrast than the noise dots. In all
      conditions the older group had higher coherence thresholds than the younger
      group, and women had higher thresholds than men. Significant correlations were
      found between coherence thresholds and self-reported driving difficulties in
      conditions in which the signal dots had to be extracted from noise only. The
      results indicate that older individuals have difficulties extracting signal from
      noise in cluttered visual environments. The implications for safe driving are
      discussed. 

PMID- 25066201
TI  - Children use salience to solve coordination problems.
AB  - Humans are routinely required to coordinate with others. When communication is
      not possible, adults often achieve this by using salient cues in the environment
      (e.g. going to the Eiffel Tower, as an obvious meeting point). To explore the
      development of this capacity, we presented dyads of 3-, 5-, and 8-year-olds (N =
      144) with a coordination problem: Two balls had to be inserted into the same of
      four boxes to obtain a reward. Identical pictures were attached to three boxes
      whereas a unique--and thus salient--picture was attached to the fourth. Children
      either received one ball each, and so had to choose the same box (experimental
      condition), or they received both balls and could get the reward independently
      (control condition). In all cases, children could neither communicate nor see
      each other's choices. Children were significantly more likely to choose the
      salient option in the experimental condition than in the control condition.
      However, only the two older age groups chose the salient box above chance levels.
      This study is the first to show that children from at least age 5 can solve
      coordination problems by converging on a salient solution.

PMID- 25066202
TI  - Cognitive variability in psychotic disorders: a cross-diagnostic cluster
      analysis.
AB  - BACKGROUND: Cognitive dysfunction is a core feature of psychotic disorders;
      however, substantial variability exists both within and between subjects in terms
      of cognitive domains of dysfunction, and a clear 'profile' of cognitive strengths
      and weaknesses characteristic of any diagnosis or psychosis as a whole has not
      emerged. Cluster analysis provides an opportunity to group individuals using a
      data-driven approach rather than predetermined grouping criteria. While several
      studies have identified meaningful cognitive clusters in schizophrenia, no study
      to date has examined cognition in a cross-diagnostic sample of patients with
      psychotic disorders using a cluster approach. We aimed to examine cognitive
      variables in a sample of 167 patients with psychosis using cluster methods.
      METHOD: Subjects with schizophrenia (n = 41), schizo-affective disorder (n = 53)
      or bipolar disorder with psychosis (n = 73) were assessed using a battery of
      cognitive and clinical measures. Cognitive data were analysed using Ward's
      method, followed by a K-means cluster approach. Clusters were then compared on
      diagnosis and measures of clinical symptoms, demographic variables and community
      functioning. RESULTS: A four-cluster solution was selected, including a
      'neuropsychologically normal' cluster, a globally and significantly impaired
      cluster, and two clusters of mixed cognitive profiles. Clusters differed on
      several clinical variables; diagnoses were distributed amongst all clusters,
      although not evenly. CONCLUSIONS: Identification of groups of patients who share
      similar neurocognitive profiles may help pinpoint relevant neural abnormalities
      underlying these traits. Such groupings may also hasten the development of
      individualized treatment approaches, including cognitive remediation tailored to
      patients' specific cognitive profiles.

PMID- 25066203
TI  - Hoodia gordonii extract targets both adipose and muscle tissue to achieve weight
      loss in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hoodia gordonii (Masson) Sweet ex Decne (family
      Apocynaceae) is consumed globally as a natural appetite suppressant. While this
      effect-and its subsequent effect of weight loss-has been reported in the
      scientific literature, no information is available on the specific tissue types
      affected that accounts for the significant weight loss reported after consumption
      of the plant. Furthermore, most studies are performed on lean animals, so that
      the response of overweight or obese individuals to this plant supplement remains
      largely unknown. MATERIALS AND METHODS: Twelve lean and twelve obese male Wistar
      rats were supplemented with different doses of Hoodia gordonii extract (80 or 160
      mg/kg body mass twice daily) in a placebo-controlled study, for a period of 14
      days. RESULTS: All supplemented rats exhibited significant weight loss (P<0.001).
      This could be ascribed to decrease in both adipose cell size and skeletal muscle
      fibre size. CONCLUSIONS: We conclude that the weight loss seen after consumption
      of Hoodia gordonii is due to loss of both adipose and muscle mass.

PMID- 25066204
TI  - Ethnomedicinal knowledge and relative importance of indigenous medicinal plants
      of Cholistan desert, Punjab Province, Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnomedicinal studies are significant for the
      discovery of new crude drugs from indigenous reported medicinal plants. The
      current study aimed to report the indigenous medicinal knowledge of plants and
      herbal remedies used as folk medicines in Cholistan desert, Punjab Province,
      Pakistan. MATERIAL AND METHODS: Rapid appraisal approach (RAA), semi-structured
      interviews, group meetings with herbalists, landowners and local people having
      awareness about the medicinal action of plants were employed to collect the data.
      RESULTS AND DISCUSSIONS: This study reports 70 medicinal plants belonging to 27
      families that were disseminated among 60 different genera and Poaceae was the
      predominant family over others with 13 reported medicinal plants. Among plant
      parts, leaves were the dominant over others with 26.4% used in herbal
      preparations followed by the stem (25.2%), fruit (21.5%), flower (16.3%), seed
      (6.5%), bark and pod (02%). Haloxylon recurvum exhibited the highest use vale
      (UV) 0.83 while least UV was exhibited by Mollugo cerviana that was 0.16.
      CONCLUSION: Important medicinal plants, reported in this study have been screened
      for phytochemical and pharmaceutical activities in different parts of the globe.
      It is recommended that reported medicinal plants having potent action for cancer
      and hepatitis must be screened for pharmacological activities.

PMID- 25066205
TI  - Surface modification for the collection and identification of fingerprints and
      colorimetric detection of urea nitrate.
AB  - Glass surfaces were modified with a combination of dyes and reagents to allow for
      the potential simultaneous recording of a detailed fingerprint and the detection
      of the explosive urea nitrate (UN), as a proof of principle of surface
      modification for simultaneous linking of identity to manipulation of explosives.
      By coating microscope slides with 9,10-diphenylanthracene (DPA), p
      dimethylaminobenzaldehyde (p-DMAB) and p-dimethylaminocinnamaldehyde (p-DMAC), a
      colorimetric change was observed in the presence of UN, while revealing a
      fingerprint with enough resolution to isolate at least 10 minutiae. This is the
      first step in creating point-of-care devices capable of detecting low
      concentrations of explosives and drug metabolites and connecting them to a
      fingerprint.

PMID- 25066206
TI  - Epithelioid hemangioma occurring in the radial styloid of a 17-year-old boy-an
      unusual presentation of an uncommon neoplasm.
AB  - Presented is a case of epithelioid hemangioma (EH) of bone occurring in the
      radial styloid of a 17-year-old boy. EH is a benign vascular tumor whose name and
      classification have changed over the years, adding potential confusion to an
      already existing diagnostic challenge. Overlapping imaging and histopathologic
      features with malignant vascular neoplasms and occasional aggressive clinical
      features have resulted in misdiagnoses and inappropriate treatment. The goal of
      this case report is to raise awareness of EH and related vascular neoplasms. 

PMID- 25066207
TI  - Management of hypersensitivity reactions to anti-D immunoglobulin preparations.
AB  - RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh
      isoimmunization. Its use has significantly reduced the incidence of haemolytic
      disease of the foetus and newborn previously responsible for one death in every
      2200 births. In pregnancy, acute drug-induced hypersensitivity reactions
      including anaphylaxis can have serious deleterious effects on the mother and
      foetus/neonate. Women can be erroneously labelled as drug allergic as the
      investigation of hypersensitivity reactions in pregnancy is complex and drug
      challenges are usually contraindicated. We present three cases of suspected anti
      D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion
      related reaction. We also propose a new algorithm for the investigations of such
      reaction. It relies on detailed history, cautious interpretation of skin tests,
      foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges.
      This is not to deprive women of anti-D which might put their future pregnancies
      at risk. 

PMID- 25066208
TI  - Application of 3-D imaging sensor for tracking minipigs in the open field test.
AB  - BACKGROUND: The minipig is a promising model in neurobiology and
      psychopharmacology. However, automated tracking of minipig behavior is still
      unresolved problem. NEW METHOD: The study was carried out on white, agouti and
      black (or spotted) minipiglets (n=108) bred in the Institute of Cytology and
      Genetics. New method of automated tracking of minipig behavior is based on
      Microsoft Kinect 3-D image sensor and the 3-D image reconstruction with
      EthoStudio software. The algorithms of distance run and time in the center
      evaluation were adapted for 3-D image data and new algorithm of vertical activity
      quantification was developed. RESULTS: The 3-D imaging system successfully
      detects white, black, spotted and agouti pigs in the open field test (OFT). No
      effect of sex or color on horizontal (distance run), vertical activities and time
      in the center was shown. Agouti pigs explored the arena more intensive than white
      or black animals, respectively. The OFT behavioral traits were compared with the
      fear reaction to experimenter. Time in the center of the OFT was positively
      correlated with fear reaction rank (rho=0.21, p<0.05). Black pigs were
      significantly more fearful compared with white or agouti animals. COMPARISON WITH
      EXISTING METHOD: The 3-D imaging system has three advantages over existing
      automated tracking systems: it avoids perspective distortion, distinguishes
      animals any color from any background and automatically evaluates vertical
      activity. CONCLUSION: The 3-D imaging system can be successfully applied for
      automated measurement of minipig behavior in neurobiological and
      psychopharmacological experiments.

PMID- 25066209
TI  - Phytochemistry and antileishmanial activity of the leaf latex of Aloe calidophila
      Reynolds.
AB  - Leishmaniasis is a major protozoal disease threatening the lives of 350 million
      people throughout the world. However, the therapeutic options for the disease are
      limited. In the present study, the antiprotozoal activity of the latex obtained
      from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro
      testing against Leishmania aethiopica and Leishmania major. It was found that the
      latex possesses moderate activity against both parasites with IC50 values of
      64.05 and 82.29 ug/mL, respectively. Phytochemical investigation resulted in the
      isolation of three anthrones identified as aloinoside, aloin, and microdontin on
      the basis of IR, MS, (1) H NMR, and (13) C NMR spectral data. The isolated
      compounds showed strong antileishmanial activity with IC50 values ranging from
      1.76 to 6.32 ug/mL against L. aethiopica and from 2.09 to 8.85 ug/mL against L.
      major. Although these values were higher than those of amphotericin B (IC50  =
      0.109 and 0.067 ug/mL), the selectivity indices (813.35 and 694.90, respectively,
      against L. aethiopica and L. major) of aloinoside were much better than those of
      the standard drug (423.49 and 688.96). The results indicate that the isolated
      compounds have the potential to be used as a scaffold for the development of safe
      and cost-effective antileishmanial agents.

PMID- 25066210
TI  - Mannose-mediated inhibitory effects of PA-MSHA on invasion and metastasis of
      hepatocellular carcinoma via EGFR/Akt/IkappaBbeta/NF-kappaB pathway.
AB  - BACKGROUND & AIMS: Elevation of high-mannose glycans is a common feature of
      malignant cells and has been suggested to be the basis for alternative cancer
      therapy for several years. Here we want to investigate the antitumour effect of
      pseudomonas aeruginosa-mannosesensitive haemagglutinin (PA-MSHA), a genetically
      engineered heat-inactivated PA strain with mannose-sensitive binding activity, on
      hepatocellular carcinoma (HCC). METHODS: Tumourigenicity and metastatic
      potentials of HCC were studied after PA-MSHA treatment by utilizing the in
      vitro/in vivo model of HCC. Expression of apoptosis-associated proteins and
      epithelial-mesenchymal transition (EMT) related genes were evaluated, and
      possible signalling pathways involved were investigated. RESULTS: PA-MSHA induced
      significant cell proliferation inhibition and cell cycle arrest of HCC through
      decreasing the levels of cyclins D1, cyclins E, CDK2, CDK4, proliferating cell
      nuclear antigen (PCNA), and increasing the level of p21 and p27. Moreover, PA
      MSHA suppressed the invasion, migration and adhesion of HCC through inhibiting
      epithelial-mesenchymal transition (EMT). PA-MSHA also inhibited
      EGFR/Akt/IkappaBbeta/NF-kappaB pathway and overexpression of NF-kappaB
      significantly abrogated PA-MSHA induced EMT inhibition. In addition, competitive
      inhibition of the mannose binding activity of PA-MSHA by D-mannose significantly
      blocked its effect on cell cycle arrest and EMT. PA-MSHA also abrogated lung
      metastasis of HCC and significantly inhibited tumour growth in the in vivo study.
      CONCLUSIONS: Our study demonstrated the essential role of EGFR/Akt/IkappaBbeta/NF
      kappaB pathway in the inhibitory effect of PA-MSHA on invasion and metastasis of
      HCC through suppressing EMT, and revealed an attractive prospect of PA-MSHA as a
      novel candidate agent in the treatment of HCC.

PMID- 25066211
TI  - Sirtuin 6 protects the heart from hypoxic damage.
AB  - Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We
      investigated whether life extension is associated with cardioprotection against
      hypoxia. The proposed study is to develop approaches to reduce hypoxic damage
      through the use of the sirtuin pathway and to elucidate the mechanism involved.
      For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over
      expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that
      cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release
      survival factors or fewer damage markers to protect them from hypoxic stress
      compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine
      kinase (CK) released to the medium and propidium iodide (PI) binding, were
      markedly decreased following hypoxia in TG cardiomyocytes. The protective
      mechanism of SIRT6 over-expression includes the activation of pAMPKalpha pathway,
      the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of
      nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB), the
      decrease of reactive oxygen species (ROS) and the reduction in the protein level
      of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes
      impede the necrosis/apoptosis pathways leading to the improved survival of
      cardiomyocytes following hypoxia, which might explain life extension. 

PMID- 25066214
TI  - Effect of dosimetric factors on occurrence and volume of temporal lobe necrosis
      following intensity modulated radiation therapy for nasopharyngeal carcinoma: a
      case-control study.
AB  - PURPOSE: To determine dosimetric risk factors for the occurrence of temporal lobe
      necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with
      intensity modulated radiation therapy (IMRT) and to investigate the impact of
      dose-volume histogram (DVH) parameters on the volume of TLN lesions (V-N).
      METHODS AND MATERIALS: Forty-three NPC patients who had developed TLN following
      IMRT and 43 control subjects free of TLN were retrospectively assessed. DVH
      parameters included maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean),
      absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), and
      doses covering certain volumes (Dvs) from 0.25 to 6.0 cm(3) (D0.25-D6.0). V-Ns
      were quantified with axial magnetic resonance images. RESULTS: DVH parameters
      were ubiquitously higher in temporal lobes with necrosis than in healthy temporal
      lobes. Increased Vds and Dvs were significantly associated with higher risk of
      TLN occurrence (P<.05). In particular, Vds at a dose of >=70 Gy were found with
      the highest odds ratios. A common increasing trend was detected between V-N and
      DVH parameters through trend tests (P for trend of <.05). Linear regression
      analysis showed that V45 had the strongest predictive power for V-N (adjusted
      R(2) = 0.305, P<.0001). V45 of <15.1 cm(3) was relatively safe as the dose
      constraint for preventing large TLN lesions with V-N of >5 cm(3). CONCLUSIONS:
      Dosimetric parameters are significantly associated with TLN occurrence and the
      extent of temporal lobe injury. To better manage TLN, it would be important to
      avoid both focal high dose and moderate dose delivered to a large area in TLs.

PMID- 25066212
TI  - The development and evaluation of a five-language multi-perspective standardised
      measure: clinical decision-making involvement and satisfaction (CDIS).
AB  - BACKGROUND: The aim of this study was to develop and evaluate a brief
      quantitative five-language measure of involvement and satisfaction in clinical
      decision-making (CDIS) - with versions for patients (CDIS-P) and staff (CDIS-S) -
      for use in mental health services. METHODS: An English CDIS was developed by
      reviewing existing measures, focus groups, semistructured interviews and
      piloting. Translations into Danish, German, Hungarian and Italian followed the
      International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task
      Force principles of good practice for translation and cultural adaptation.
      Psychometricevaluation involved testing the measure in secondary mental health
      services in Aalborg, Debrecen, London, Naples, Ulm and Zurich. RESULTS: After
      appraising 14 measures, the Control Preference Scale and Satisfaction With
      Decision-making English-language scales were modified and evaluated in interviews
      (n = 9), focus groups (n = 22) and piloting (n = 16). Translations were validated
      through focus groups (n = 38) and piloting (n = 61). A total of 443 service users
      and 403 paired staff completed CDIS. The Satisfaction sub-scale had internal
      consistency of 0.89 (0.86-0.89 after item-level deletion) for staff and 0.90
      (0.87-0.90) for service users, both continuous and categorical (utility) versions
      were associated with symptomatology and both staff-rated and service userrated
      therapeutic alliance (showing convergent validity), and not with social
      disability (showing divergent validity), and satisfaction predicted staff-rated
      (OR 2.43, 95%CI 1.54- 3.83 continuous, OR 5.77, 95%CI 1.90-17.53 utility) and
      service user-rated (OR 2.21, 95%CI 1.51-3.23 continuous, OR 3.13, 95%CI 1.10-8.94
      utility) decision implementation two months later. The Involvement sub-scale had
      appropriate distribution and no floor or ceiling effects, was associated with
      stage of recovery, functioning and quality of life (staff only) (showing
      convergent validity), and not with symptomatology or social disability (showing
      divergent validity), and staff-rated passive involvement by the service user
      predicted implementation (OR 3.55, 95%CI 1.53-8.24). Relationships remained after
      adjusting for clustering by staff. CONCLUSIONS: CDIS demonstrates adequate
      internal consistency, no evidence of item redundancy, appropriate distribution,
      and face, content, convergent, divergent and predictive validity. It can be
      recommended for research and clinical use. CDIS-P and CDIS-S in all 3 five
      languages can be downloaded at http://www.cedar-net.eu/instruments. TRIAL
      REGISTRATION: ISRCTN75841675.

PMID- 25066215
TI  - Volumetric spectroscopic imaging of glioblastoma multiforme radiation treatment
      volumes.
AB  - PURPOSE: Magnetic resonance (MR) imaging and computed tomography (CT) are used
      almost exclusively in radiation therapy planning of glioblastoma multiforme
      (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI)
      can identify biochemical patterns associated with normal brain and tumor,
      predominantly by observation of choline (Cho) and N-acetylaspartate (NAA)
      distributions. In this study, volumetric 3-dimensional MRSI was used to map these
      compounds over a wide region of the brain and to evaluate metabolite-defined
      treatment targets (metabolic tumor volumes [MTV]). METHODS AND MATERIALS:
      Volumetric MRSI with effective voxel size of ~1.0 mL and standard clinical MR
      images were obtained from 19 GBM patients. Gross tumor volumes and edema were
      manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were
      defined (CTV46 and CTV60, respectively). MTVCho and MTVNAA were constructed based
      on volumes with high Cho and low NAA relative to values estimated from normal
      appearing tissue. RESULTS: The MRSI coverage of the brain was between 70% and
      76%. The MTVNAA were almost entirely contained within the edema, and the
      correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast,
      a considerable fraction of MTVCho was outside of the edema (median, 33%) and for
      some patients it was also outside of the CTV46 and CTV60. These untreated volumes
      were greater than 10% for 7 patients (37%) in the study, and on average more than
      one-third (34.3%) of the MTVCho for these patients were outside of CTV60.
      CONCLUSIONS: This study demonstrates the potential usefulness of whole-brain MRSI
      for radiation therapy planning of GBM and revealed that areas of metabolically
      active tumor are not covered by standard RT volumes. The described integration of
      MTV into the RT system will pave the way to future clinical trials investigating
      outcomes in patients treated based on metabolic information.

PMID- 25066216
TI  - Myoepithelioma of bone with a novel FUS-POU5F1 fusion gene.
AB  - AIMS: Myoepithelial tumours of soft tissue are rare lesions with a broad
      morphological and clinical spectrum. Previous studies have found EWSR1
      rearrangements in approximately half of all cases and PBX1, ZNF44 and POU5F1 have
      been identified as recurrent fusion partners. In bone, only a small number of
      myoepithelial tumours have been described. We investigated an intraosseous
      myoepithelioma of the sacrum in a 54-year-old man without EWSR1 rearrangement for
      the presence of other fusion genes. METHODS AND RESULTS: G-banding analysis, SNP
      array and fluorescence in situ hybridisation suggested rearrangement of the FUS
      and POU5F1 genes. RT-PCR confirmed a chimeric in-frame transcript fusing FUS exon
      5 to POU5F1 exon 2. The clinical course after en bloc resection was without
      recurrence or metastasis over a period of 87 months. CONCLUSION: We report a
      novel FUS-POU5F1 fusion gene in an intraosseous myoepithelioma of the sacrum.
      This case highlights that FUS can replace EWSR1 as the N-terminal transactivator
      in oncogenic fusion genes in myoepithelial tumours, similar to that which has
      previously been demonstrated in other tumour entities. Thus, in addition to
      EWSR1, also FUS needs to be considered as a potential fusion partner in the
      molecular work up of myoepithelial tumours.

PMID- 25066217
TI  - Microtensile bond strength of different acrylic teeth to high-impact denture base
      resins.
AB  - PURPOSE: This study evaluated the effect of denture base acrylic, denture tooth
      composition, and ridge-lap surface treatment on the microtensile bond strength
      (MUTBS) of three commercially available denture teeth and two injection denture
      processing systems. MATERIALS AND METHODS: Sixteen experimental groups were
      formed (n = 3), according to denture tooth surface treatment (no treatment or
      surface treatment recommended by the manufacturer), denture base processing
      technique and acrylic (SR-Ivocap-Ivocap Plus or Success-Lucitone 199), and tooth
      type-composition at bonding interface (BlueLine DCL-PMMA, Portrait IPN-PMMA,
      Phonares II-PMMA, Phonares II-NHC). Rectangular bar specimens with a 1 mm(2)
      cross sectional area were fabricated and subsequently thermocycled at 10,000
      cycles between 5 degrees C and 55 degrees C with a 15-second dwell time. Select
      specimens underwent MUTBS testing in a universal testing machine with a 1 kN load
      cell at 0.5 mm/min crosshead speed. Data were analyzed statistically by two and
      three-way ANOVA and Tukey post hoc test (alpha = 0.05). RESULTS: Mean MUTBS
      ranged between 56.2 +/- 5.6 and 60.8 +/- 5.0 N/mm(2) for the Ivocap Plus
      specimens and 13.3 +/- 5.12 to 60.1 +/- 6.0 N/mm(2) for the Lucitone 199
      specimens. Among the Ivocap specimens, BlueLine DCL and Phonares II NHC had
      significantly higher MUTBS than Portrait IPN to Ivocap Plus acrylic. There were
      no statistically significant differences among Blueline, Phonares II PMMA, and
      Phonares II NHC, or between Phonares II PMMA and Portrait IPN. Within the
      Luctione 199 specimens, there was a significantly higher MUTBS for BlueLine DCL
      and Phonares II NHC denture teeth with the manufacturer-recommended surface
      treatment when compared to control surface. BlueLine, Portrait, and Phonares II
      PMMA groups achieved significantly higher mean MUTBS than the Phonares II NHC
      group. There were no statistically significant differences among BlueLine,
      Portrait, and Phonares II PMMA groups. CONCLUSION: When evaluating the MUTBS of
      PMMA and NHC denture teeth to base resins, a stronger bond was achieved using
      materials produced by the same manufacturer. Within the Luctione 199 specimens,
      the Phonares II NHC group demonstrated significantly lower bond strength than
      other specimens, suggesting that gross ridge-lap reduction of NHC denture teeth
      is not recommended if a base acrylic by a different manufacturer from the tooth
      is going to be used.

PMID- 25066218
TI  - IGF-I sensitivity in Silver-Russell syndrome with IGF2/H19 hypomethylation.
AB  - BACKGROUND: Silver-Russell syndrome (SRS) is characterized by intrauterine and
      postnatal growth retardation, typical facial appearance and body asymmetry. The
      mechanism of growth retardation is unclear. 50% of the patients have a paternal
      chromosome 11 epimutation-DNA hypomethylation of the imprinting center region 1
      (ICR1) of the insulin-like growth factor 2 (IGF2)/H19 locus. SRS children who
      carry such an epimutation have increased levels of IGF-I and IGFBP-3 in relation
      to their stature and body weight, suggesting IGF-I resistance. No IGF-I receptor
      (IGF-1R) defect has been discovered. Therefore, another mechanism, probably an
      IGF-I post-receptor signaling defect, might be present. OBJECTIVE: The aim of
      this in-vitro study was to examine: 1) if IGF-I- and IGF-II-induced fibroblast
      growth is different in SRS children with IGF2/H19 hypomethylation compared to
      controls; and 2) whether there is IGF-I insensitivity in this subgroup of SRS
      children due to IGF-I post-receptor signaling defects. DESIGN: Four SRS patients
      (two males, two females; 9.2 to 16.6 years of age) with an IGF2/H19
      hypomethylation defect and three age-matched healthy controls were included in
      the in-vitro study. Cultivated skin fibroblasts from the patients and the healthy
      controls were used for the experiments. Proliferation rates of fibroblasts were
      measured in the presence or absence of recombinant human IGF-I and IGF-II using
      the commercially available 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test. PI3K
      (phosphoinositide 3-kinase) assay and NF-kappaB transcription factor assay were
      performed using ELISA in order to estimate the IGF-I-stimulated Akt
      phosphorylation and IkappaB phosphorylation, respectively. RESULTS: Fibroblasts
      from SRS patients and fibroblasts from control individuals showed a comparable
      potential to proliferate in serum-free medium when stimulated with IGFs. No
      significant differences were found between both groups concerning Akt
      phosphorylation and IkappaB phosphorylation rates. CONCLUSIONS: The results of
      the in-vitro study do not support the hypothesis that IGF-I/IGF-II resistance is
      a major pathogenetic mechanism responsible for the growth failure in the subgroup
      of SRS children with IGF2/H19 hypomethylation.

PMID- 25066219
TI  - Are Niemann-Pick type C proteins key players in cnidarian-dinoflagellate
      endosymbioses?
AB  - The symbiotic interaction between cnidarians, such as corals and sea anemones,
      and the unicellular algae Symbiodinium is regulated by yet poorly understood
      cellular mechanisms, despite the ecological importance of coral reefs. These
      mechanisms, including host-symbiont recognition and metabolic exchange, control
      symbiosis stability under normal conditions, but also lead to symbiosis breakdown
      (bleaching) during stress. This study describes the repertoire of the sterol
      trafficking proteins Niemann-Pick type C (NPC1 and NPC2) in the symbiotic sea
      anemone Anemonia viridis. We found one NPC1 gene in contrast to the two genes
      (NPC1 and NPC1L1) present in vertebrate genomes. While only one NPC2 gene is
      present in many metazoans, this gene has been duplicated in cnidarians, and we
      detected four NPC2 genes in A. viridis. However, only one gene (AvNPC2-d) was
      upregulated in symbiotic relative to aposymbiotic sea anemones and displayed
      higher expression in the gastrodermis (symbiont-containing tissue) than in the
      epidermis. We performed immunolabelling experiments on tentacle cross sections
      and demonstrated that the AvNPC2-d protein was closely associated with
      symbiosomes. In addition, AvNPC1 and AvNPC2-d gene expression was strongly
      downregulated during stress. These data suggest that AvNPC2-d is involved in both
      the stability and dysfunction of cnidarian-dinoflagellate symbioses.

PMID- 25066213
TI  - Consortium analysis of gene and gene-folate interactions in purine and pyrimidine
      metabolism pathways with ovarian carcinoma risk.
AB  - SCOPE: We reevaluated previously reported associations between variants in
      pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC)
      risk, and in related pathways of purine and pyrimidine metabolism, and assessed
      interactions with folate intake. METHODS AND RESULTS: Odds ratios (OR) for 446
      genetic variants were estimated among 13,410 OC cases and 22,635 controls, and
      among 2281 cases and 3444 controls with folate information. Following multiple
      testing correction, the most significant main effect associations were for
      dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 * 10
      5) and rs828054 (OR = 1.06; p = 1 * 10-4). Thirteen variants in the pyrimidine
      metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with
      folate in a multivariant analysis (corrected p = 9.9 * 10-6) but collectively
      explained only 0.2% of OC risk. Although no other associations were significant
      after multiple testing correction, variants in SHMT1 in 1-C transfer, previously
      reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03
      0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD,
      which was previously reported to be associated with OC, may influence risk;
      however, stratification by folate intake is unlikely to modify disease risk
      appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but
      require further validation. Polymorphisms in selected genes in purine metabolism
      were not associated with OC.

PMID- 25066220
TI  - Hirschsprung's disease prevalence in Europe: a register based study.
AB  - BACKGROUND: Hirschsprung's disease is a congenital gut motility disorder,
      characterised by the absence of the enteric ganglion cells along the distal gut.
      The aim of this study was to describe the epidemiology of Hirschsprung's disease,
      including additional congenital anomalies, total prevalence, trends, and
      association with maternal age. METHODS: Cases of Hirschsprung's disease delivered
      during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly
      registers formed the population-based case-series. Prevalence rates and 95%
      confidence intervals were calculated as the number of cases per 10,000 births.
      Multilevel Poisson regression was performed to investigate trends in prevalence,
      geographical variation and the association with maternal age. RESULTS: There were
      1,322 cases of Hirschsprung's disease among 12,146,210 births. The total
      prevalence was 1.09 (95% confidence interval, 1.03-1.15) per 10,000 births and
      there was a small but significant increase in prevalence over time (relative risk
      = 1.01; 95% credible interval, 1.00-1.02; p = 0.004). There was evidence of
      geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases
      with chromosomal anomalies or genetic syndromes, there were 1,176 cases
      (prevalence = 0.97; 95% confidence interval, 0.91-1.03 per 10,000 births), of
      which 137 (11.6%) had major structural anomalies. There was no evidence of a
      significant increased risk of Hirschsprung's disease in cases born to women aged
      >=35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible
      interval, 0.91-1.31; p = 0.355). CONCLUSION: This large population-based study
      found evidence of a small increasing trend in Hirschsprung's disease and
      differences in prevalence by geographic location. There was also no evidence of
      an association with maternal age.

PMID- 25066221
TI  - Activity of cabazitaxel after docetaxel and abiraterone acetate therapy in
      patients with castration-resistant prostate cancer.
AB  - BACKGROUND: Cabazitaxel and AA have been approved by the US Food and Drug
      Administration for use after docetaxel in mCRPC. Recently, CAB appeared to be
      active when given after AA. AA is capable of inducing AR splice variants that
      confer ligand-independent AR transactivation. Because microtubule-targeting
      agents impair AR nuclear transport and activity, we raised concerns about CAB
      efficacy after AA failure in mCRPC. PATIENTS AND METHODS: One hundred thirty
      mCRPC patients received AA after docetaxel treatment in compassionate programs.
      Of them, 24 (18.4%) subsequently received CAB. We retrospectively reviewed their
      data using conventional methods. RESULTS: Twenty-four patients received a median
      of 4 (range, 1-13) CAB cycles. Nineteen (79.1%) of them received primary
      prophylaxis with growth factors. Median patient characteristics were: age 65
      (range, 57-85) years; Gleason score: 8 (range, 6-10); and PSA: 128.1 (range, 0.01
      1700) ng/mL. A PSA response (>= 50% decrease from baseline) occurred in 6 (31.5%)
      of 19 evaluable patients (95% confidence interval [CI], 11.8-54.2%). CAB therapy
      obtained a partial response in 2 of the 13 (15.3%) evaluable patients (95% CI,
      2.9-45.4%). Median survival from initiation of CAB was 8.2 (95% CI, 3.34-13.05)
      months, from AA 16.1 (95% CI, 11.56-20.64) and from docetaxel 32.0 (95% CI, 11.56
      39.69). CONCLUSION: A limited number of patients with mCRPC received CAB after
      docetaxel and AA treatment. In this selected population, CAB was active.

PMID- 25066222
TI  - Palladium-catalyzed synthesis of ammonium sulfinates from aryl halides and a
      sulfur dioxide surrogate: a gas- and reductant-free process.
AB  - Sulfonyl-derived functional groups populate a broad range of useful molecules and
      materials, and despite a variety of preparative methods being available,
      processes which introduce the most basic sulfonyl building block, sulfur dioxide,
      using catalytic methods, are rare. Described herein is a simple reaction system
      consisting of the sulfur dioxide surrogate DABSO, triethylamine, and a
      palladium(0) catalyst for effective convertion of a broad range of aryl and
      heteroaryl halides into the corresponding ammonium sulfinates. Key features of
      this gas- and reductant-free reaction include the low loadings of palladium (1
      mol%) and ligand (1.5 mol%) which can be employed, and the use of isopropyl
      alcohol as both a solvent and formal reductant. The ammonium sulfinate products
      are converted in situ into a variety of sulfonyl-containing functional groups,
      including sulfones, sulfonyl chlorides, and sulfonamides.

PMID- 25066223
TI  - Metacognitive group training for schizophrenia spectrum patients with delusions:
      a randomized controlled trial.
AB  - BACKGROUND: Metacognitive training (MCT) for patients with psychosis is a
      psychological group intervention that aims to educate patients about common
      cognitive biases underlying delusion formation and maintenance, and to highlight
      their negative consequences in daily functioning. METHOD: In this randomized
      controlled trial, 154 schizophrenia spectrum patients with delusions were
      randomly assigned to either MCT + treatment as usual (TAU) or TAU alone. Both
      groups were assessed at baseline, and again after 8 and 24 weeks. The trial was
      completed fully by 111 patients. Efficacy was measured with the Psychotic Symptom
      Rating Scales (PSYRATS) Delusions Rating Scale (DRS), and with specific secondary
      measures referring to persecutory ideas and ideas of social reference (the Green
      Paranoid Thoughts Scale, GPTS), cognitive insight (the Beck Cognitive Insight
      Scale, BCIS), subjective experiences of cognitive biases (the Davos Assessment of
      Cognitive Biases Scale, DACOBS) and metacognitive beliefs (the 30-item
      Metacognitions Questionnaire, MCQ-30). Economic analysis focused on the balance
      between societal costs and health outcomes (quality-adjusted life years, QALYs).
      RESULTS: Both conditions showed a decrease of delusions. MCT was not more
      efficacious in terms of reducing delusions, nor did it change subjective paranoid
      thinking and ideas of social reference, cognitive insight or subjective
      experience of cognitive biases and metacognitive beliefs. The results of the
      economic analysis were not in favour of MCT + TAU. CONCLUSIONS: In the present
      study, MCT did not affect delusion scores and self-reported cognitive insight, or
      subjective experience of cognitive biases and metacognitive beliefs. MCT was not
      cost-effective.

PMID- 25066224
TI  - Higher titers of anti-Chlamydia pneumoniae IgG in diabetic retinopathy: a cross
      sectional study.
AB  - BACKGROUND: Chronic inflammation has a role in the pathogenesis of diabetic
      retinopathy. Infection with intracellular organisms may incite chronic
      inflammation. This study was conducted to investigate the association between
      previous infection with Chlamydia pneumoniae (an intracellular microorganism) and
      diabetic retinopathy. METHODS: Patients with type 2 diabetes mellitus (30-60
      years old) and age-matched normal controls were recruited. Patients with history
      of cardiovascular or cerebrovascular disease, recent pulmonary infection and the
      presence of age-related macular degeneration were excluded from the study.
      Complete ophthalmic examinations were performed. Fasting blood sugar and
      haemoglobin levels were measured in diabetic patients and controls, and HgbA1c ,
      blood urea nitrogen, creatinine and 24-h urine protein were measured in diabetic
      patients. Anti-C. pneumoniae IgG (enzyme-linked immunosorbent assay) was measured
      in the sera of all participants. RESULTS: A total of 215 type 2 diabetic patients
      and 243 normal healthy controls were included. Anti-C. pneumoniae IgG titers were
      higher in patients affected by diabetic retinopathy than participants without
      retinopathy (74.78 +/- 33.38 vs 66.18 +/- 31.40, p = 0.028). Diabetic patients
      with diabetic retinopathy also had higher titers than diabetic patients without
      diabetic retinopathy (74.78 +/- 33.38 vs 66.11 +/- 33.41, p = 0.042). Of
      different variables including age, body mass index, haemoglobin level, glycated
      haemoglobin level, fasting blood sugar, mean arterial pressure and blood urea
      nitrogen, only age (r = 0.17; p = 0.001) and body mass index (r = 0.15; p =
      0.003) were correlated with anti-C. pneumoniae IgG levels. In regression
      analysis, the presence of diabetic retinopathy was still a determinant of the
      antibody level (p = 0.03). CONCLUSION: Anti-C. pneumoniae IgG titers were higher
      in patients with diabetic retinopathy, which may indicate a role of this
      infection in the pathogenesis of diabetic retinopathy.

PMID- 25066225
TI  - CD271 is expressed in melanomas with more aggressive behaviour, with correlation
      of characteristic morphology by in vivo reflectance confocal microscopy.
AB  - BACKGROUND: Melanoma is the most highly aggressive type of skin cancer. Its
      resistance to existing treatments and the rapid rise in incidence underscore the
      importance of acquiring a better understanding of melanomagenesis. OBJECTIVES: To
      assess the impact of reflectance confocal microscopy (RCM) on the description of
      cell morphology, which may influence the growth pattern and changes with
      increasing tumour severity, correlating with biological aspects. METHODS: A
      retrospective analysis of 30 primary melanomas in vivo, evaluated by RCM, to
      correlate cell morphology and cellular arrangement with a marker of melanoma
      progression (CD271) using immunohistochemical evaluations. RESULTS: Typical cells
      organized in dermal nests with peculiar in vivo confocal morphology result in
      melanoma with high malignancy and positivity to CD271. This architecture might be
      due to the presence of a type of cells, intrinsically predisposed to invasion, as
      a result of dedifferentiation programming, revealed by expression of the neural
      crest marker CD271. CONCLUSIONS: With the hypothesis that dedifferentiated cells
      would be strongly responsible for initiation of tumour development and
      progression, we propose that CD271 detection could be associated with RCM
      evaluation in order to detect more aggressive melanoma subtypes.

PMID- 25066226
TI  - Utility of a population pharmacokinetic meta analysis during the approval process
      of teduglutide for the treatment of short bowel syndrome.
AB  - OBJECTIVE: Teduglutide is a recombinant analogue of human glucagonlike peptide-2
      (GLP-2) that was recently approved by the US and European regulatory agencies FDA
      and EMA for the treatment of short bowel syndrome (SBS). The objectives of this
      work were, firstly, to develop a population pharmacokinetic (popPK) model based
      on the available PK data of the entire clinical development program and,
      secondly, to utilize the model for the justification of the proposed dosing
      regimen. The exploratory analysis was based on a previously established
      structural PK model and focused primarily on the investigation of covariate
      effects. RESULTS: The plasma concentrationtime profiles of teduglutide after
      subcutaneous application were adequately described by a 1-compartment model with
      first order absorption and elimination. The area under the curve (AUC) was lower
      for male subjects, for subjects with higher creatinine clearance, for overweight
      subjects, and for SBS patients. However, except for subjects with severe renal
      impairment no clinically relevant effects on AUC were identified. CONCLUSION: Our
      model-based analysis supports the approved dose adjustment for SBS patients with
      and without renal impairments maintaining the exposure in a value range with
      acceptable variance for the target population.

PMID- 25066227
TI  - Impact of comorbidities on the treatment of atopic dermatitis in clinical
      practice.
AB  - BACKGROUND AND AIM: Atopic dermatitis is often associated with atopic
      comorbidities such as allergic rhinitis, allergic asthma and food allergy. The
      aim of the present study was to analyze treatment data pertaining to atopic
      dermatitis patients in Germany with regard to the presence of other atopic
      comorbidities in the primary care and to investigate whether the presence of
      atopic codiagnoses has an impact on the treatment of atopic dermatitis (AD)
      patients. METHODS: We used data from the Disease Analyzer database (IMS HEALTH,
      Germany) including 1,631 physicians (general practitioners, dermatologists and
      pediatricians) and 3.3 million patients. 39,642 (7.5%) of these patients were
      treated by dermatologists, 17,124 (5.2%) by pediatricians and 15,774 (0.9%) by
      general practitioners and had a documented diagnosis of atopic dermatitis.
      RESULTS: 46.4% of AD patients treated by general practitioners, 42.5% by
      dermatologists and 32.0% by pediatricians were codiagnosed with one defined
      atopic diseases (allergic asthma, urticaria, allergic rhinitis and food allergy).
      In patients without AD, the proportion of atopic diseases was significantly
      smaller (41.4% for those treated by general practitioners, 38.4% for those
      treated by dermatologists, 26.4% for those treated by pediatricians). AD patients
      with another atopic comorbidity received topical corticosteroids (CS) (42.5%)
      more frequently than those without comorbidity (46.4% vs. 41.4% for patients
      treated by general practitioners, 42.5% vs. 38.4% for patients treated by
      dermatologists, 32.0% vs. 26.4% for patients treated by pediatricians). The
      general practitioners and pediatricians prescribed systemic corticosteroids to
      13.2% and 7.8% of AD patients with additional atopic diseases, while the rate was
      only 5.1% and 3.0% in patients without comorbidities. CONCLUSION: In AD patients,
      the share of patients diagnosed with atopic diseases is significantly higher than
      in patients without AD. AD outpatients with concomitant atopic comorbidities
      receive topical, but also systemic corticosteroid prescriptions more frequently.

PMID- 25066228
TI  - Adverse drug reactions in elderly patients following discharge from an internal
      medicine clinic.
AB  - OBJECTIVE: The aim of this study was to evaluate the incidence and type of
      adverse drug reactions (ADRs) and identify risk factors for ADRs in elderly
      patients within 30 days following discharge from an internal medicine clinic.
      METHODS: A prospective observational study was conducted at the Internal Medicine
      Clinic of University Hospital Dubrava, Zagreb, Croatia, between September 1(st)
      and November 30(th) 2012. Patients aged >= 65 years discharged from the clinic
      during the study period were eligible for inclusion in the study. The follow-up
      visit was scheduled ~ 30 days after discharge. During the visit, the patients
      were assessed for the occurrence of ADRs. Two independent physicians evaluated
      each possible ADR by using the Naranjo ADR probability scale. Multivariate
      logistic regression analysis was used to identify predisposing factors for ADRs.
      RESULTS: There were 209 patients included in this study. A total of 72 ADRs were
      detected in 63 (30.1%) patients. The most frequent ADRs were bleeding disorders
      associated with warfarin therapy, followed by hypoglycemia associated with
      antidiabetics. Five (6.9%) ADRs, which resulted in hospital admission, were
      classified as serious. Multivariate logistic regression analysis indicated number
      of prescribed drugs >=4 and prescription of furosemide and warfarin to be
      associated with increased risk of ADRs. CONCLUSIONS: Our study showed that ADRs
      are an important cause of morbidity in elderly patients after hospital discharge.
      Judicious prescription of drugs and careful and frequent monitoring of drug
      therapy are necessary to reduce the risk of ADRs.

PMID- 25066230
TI  - Directional drop transport achieved on high-temperature anisotropic wetting
      surfaces.
AB  - The surfaces of ambient-temperature superhydrophilic tilting silicon nanowires
      (TSNWs) exhibit an anisotropic wetting performance at high temperature and a
      deposited drop moves directionally on this surface. A vapor film forming beneath
      the drop after spreading reduces the surface friction and the heat transfer
      efficiency between the drop and the surface, so the drop moves with a constant
      speed and little mass loss. 

PMID- 25066229
TI  - Glucagon-like peptide-1 receptor agonists as insulin add-on therapy in patients
      with inadequate glycemic control in type 2 diabetes mellitus: lixisenatide as a
      new therapeutic option.
AB  - Despite the variety of therapeutic options for the management of type 2 diabetes
      mellitus, many patients fail to meet glycated hemoglobin (HbA1c) targets. The
      relative contribution of postprandial plasma glucose (PPG) to overall HbA1c is
      estimated at 40-60%, with the effect of PPG on HbA1c being prominent in patients
      on basal insulin. The development of glucagon-like peptide-1 receptor agonists
      (GLP-1RAs) has been an important achievement in diabetes management and has
      become an established treatment. Of available GLP-1RAs, lixisenatide is a once
      daily prandial GLP-1RA that has been shown to produce a reduction in HbA1c with a
      pronounced postprandial effect, suggesting a complementary effect between
      lixisenatide and basal insulin on PPG and fasting plasma glucose, resulting in a
      beneficial effect on body weight in all populations. Therefore, lixisenatide will
      make an important addition to current options for treating diabetes, especially
      for patients not achieving glycemic targets with basal insulin therapy.

PMID- 25066231
TI  - SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break
      perinuclear anchorage site choice.
AB  - Persistent DNA double-strand breaks (DSBs) are recruited to the nuclear periphery
      in budding yeast. Both the Nup84 pore subcomplex and Mps3, an inner nuclear
      membrane (INM) SUN domain protein, have been implicated in DSB binding. It was
      unclear what, if anything, distinguishes the two potential sites of repair. Here,
      we characterize and distinguish the two binding sites. First, DSB-pore
      interaction occurs independently of cell-cycle phase and requires neither the
      chromatin remodeler INO80 nor recombinase Rad51 activity. In contrast, Mps3
      binding is S and G2 phase specific and requires both factors. SWR1-dependent
      incorporation of Htz1 (H2A.Z) is necessary for break relocation to either site in
      both G1- and S-phase cells. Importantly, functional assays indicate that
      mutations in the two sites have additive repair defects, arguing that the two
      perinuclear anchorage sites define distinct survival pathways.

PMID- 25066232
TI  - Frequent Interchromosomal Template Switches during Gene Conversion in S.
      cerevisiae.
AB  - Although repair of double-strand breaks (DSBs) by gene conversion is the most
      accurate way to repair such lesions, in budding yeast there is a 1,000-fold
      increase in accompanying mutations, including interchromosomal template switches
      (ICTS) involving highly mismatched (homeologous) ectopic sequences. Although such
      events are rare and appear at a rate of 2 * 10(-7) when template jumps occur
      between 71% identical sequences, they are surprisingly frequent (0.3% of all
      repair events) when the second template is identical to the first, revealing the
      remarkable instability of repair DNA synthesis. With homeologous donors, ICTS
      uses microhomologies as small as 2 bp. Cells lacking mismatch repair proteins
      Msh6 and Mlh1 form chimeric recombinants with two distinct patches of
      microhomology, implying that these proteins are crucial for strand discrimination
      of heteroduplex DNA formed during ICTS. We identify the chromatin remodeler Rdh54
      as the first protein required for template switching that does not affect simple
      gene conversion.

PMID- 25066233
TI  - Hierarchical molecular events driven by oocyte-specific factors lead to rapid and
      extensive reprogramming.
AB  - Nuclear transfer to oocytes is an efficient way to transcriptionally reprogram
      somatic nuclei, but its mechanisms remain unclear. Here, we identify a sequence
      of molecular events that leads to rapid transcriptional reprogramming of somatic
      nuclei after transplantation to Xenopus oocytes. RNA-seq analyses reveal that
      reprogramming by oocytes results in a selective switch in transcription toward an
      oocyte rather than pluripotent type, without requiring new protein synthesis.
      Time-course analyses at the single-nucleus level show that transcriptional
      reprogramming is induced in most transplanted nuclei in a highly hierarchical
      manner. We demonstrate that an extensive exchange of somatic- for oocyte-specific
      factors mediates reprogramming and leads to robust oocyte RNA polymerase II
      binding and phosphorylation on transplanted chromatin. Moreover, genome-wide
      binding of oocyte-specific linker histone B4 supports its role in transcriptional
      reprogramming. Thus, our study reveals the rapid, abundant, and stepwise loading
      of oocyte-specific factors onto somatic chromatin as important determinants for
      successful reprogramming. 

PMID- 25066234
TI  - Requirement for PBAF in transcriptional repression and repair at DNA breaks in
      actively transcribed regions of chromatin.
AB  - Actively transcribed regions of the genome are vulnerable to genomic instability.
      Recently, it was discovered that transcription is repressed in response to
      neighboring DNA double-strand breaks (DSBs). It is not known whether a failure to
      silence transcription flanking DSBs has any impact on DNA repair efficiency or
      whether chromatin remodelers contribute to the process. Here, we show that the
      PBAF remodeling complex is important for DSB-induced transcriptional silencing
      and promotes repair of a subset of DNA DSBs at early time points, which can be
      rescued by inhibiting transcription globally. An ATM phosphorylation site on
      BAF180, a PBAF subunit, is required for both processes. Furthermore, we find that
      subunits of the PRC1 and PRC2 polycomb group complexes are similarly required for
      DSB-induced silencing and promoting repair. Cancer-associated BAF180 mutants are
      unable to restore these functions, suggesting PBAF's role in repressing
      transcription near DSBs may contribute to its tumor suppressor activity. 

PMID- 25066235
TI  - Molecular basis for coordinating transcription termination with noncoding RNA
      degradation.
AB  - The Nrd1-Nab3-Sen1 (NNS) complex is essential for controlling pervasive
      transcription and generating sn/snoRNAs in S. cerevisiae. The NNS complex
      terminates transcription of noncoding RNA genes and promotes exosome-dependent
      processing/degradation of the released transcripts. The Trf4-Air2-Mtr4 (TRAMP)
      complex polyadenylates NNS target RNAs and favors their degradation. NNS
      dependent termination and degradation are coupled, but the mechanism underlying
      this coupling remains enigmatic. Here we provide structural and functional
      evidence demonstrating that the same domain of Nrd1p interacts with RNA
      polymerase II and Trf4p in a mutually exclusive manner, thus defining two
      alternative forms of the NNS complex, one involved in termination and the other
      in degradation. We show that the Nrd1-Trf4 interaction is required for optimal
      exosome activity in vivo and for the stimulation of polyadenylation of NNS
      targets by TRAMP in vitro. We propose that transcription termination and RNA
      degradation are coordinated by switching between two alternative partners of the
      NNS complex. 

PMID- 25066237
TI  - Outcomes of atrio-esophageal fistula following catheter ablation of atrial
      fibrillation treated with surgical repair versus esophageal stenting.

PMID- 25066238
TI  - Evidence of a conserved role for Chlamydia HtrA in the replication phase of the
      chlamydial developmental cycle.
AB  - Identification of the HtrA inhibitor JO146 previously enabled us to demonstrate
      an essential function for HtrA during the mid-replicative phase of the Chlamydia
      trachomatis developmental cycle. Here we extend our investigations to other
      members of the Chlamydia genus. C. trachomatis isolates with distinct replicative
      phase growth kinetics showed significant loss of viable infectious progeny after
      HtrA was inhibited during the replicative phase. Mid-replicative phase addition
      of JO146 was also significantly detrimental to Chlamydia pecorum, Chlamydia suis
      and Chlamydia cavie. These data combined indicate that HtrA has a conserved
      critical role during the replicative phase of the chlamydial developmental cycle.

PMID- 25066236
TI  - Pseudomonas aeruginosa AmpR: an acute-chronic switch regulator.
AB  - Pseudomonas aeruginosa is one of the most intractable human pathogens that pose
      serious clinical challenge due to extensive prevalence of multidrug-resistant
      clinical isolates. Armed with abundant virulence and antibiotic resistance
      mechanisms, it is a major etiologic agent in a number of acute and chronic
      infections. A complex and intricate network of regulators dictates the expression
      of pathogenicity factors in P. aeruginosa. Some proteins within the network play
      key roles and control multiple pathways. This review discusses the role of one
      such protein, AmpR, which was initially recognized for its role in antibiotic
      resistance by regulating AmpC beta-lactamase. Recent genomic, proteomic and
      phenotypic analyses demonstrate that AmpR regulates expression of hundreds of
      genes that are involved in diverse pathways such as beta-lactam and non-beta
      lactam resistance, quorum sensing and associated virulence phenotypes, protein
      phosphorylation, and physiological processes. Finally, ampR mutations in clinical
      isolates are reviewed to shed light on important residues required for its
      function in antibiotic resistance. The prevalence and evolutionary implications
      of AmpR in pathogenic and nonpathogenic proteobacteria are also discussed. A
      comprehensive understanding of proteins at nodal positions in the P. aeruginosa
      regulatory network is crucial in understanding, and ultimately targeting, the
      pathogenic stratagems of this organism.

PMID- 25066240
TI  - Finding A Seat at the Table Together: Recommendations for Improving Collaboration
      between Social Work and Bioethics.
AB  - Social work and bioethics are fields deeply committed to cross-disciplinary
      collaboration to do their respective work. While scholars and practitioners from
      both fields share a commitment to social justice and to respecting the dignity,
      integrity and the worth of all persons, the overlap between the fields, including
      shared values, has received little attention. The purpose of this article is to
      describe the ways in which greater collaboration between the two fields can
      broaden their scope, enrich their scholarship, and better ground their practice.
      We describe the potential for realizing such benefits in two areas - health care
      ethics consultation and social inequalities in health - arguing that the fields
      both complement and challenge one another, making them ideal partners for the
      interdisciplinary inquiry and problem-solving so often called for today in health
      and health care. 

PMID- 25066239
TI  - Brain white matter integrity and cortisol in older men: the Lothian Birth Cohort
      1936.
AB  - Elevated glucocorticoid (GC) levels are hypothesized to be deleterious to some
      brain regions, including white matter (WM). Older age is accompanied by increased
      between-participant variation in GC levels, yet relationships between WM
      integrity and cortisol levels in older humans are underexplored. Moreover, it is
      unclear whether GC-WM associations might be general or pathway specific. We
      analyzed relationships between salivary cortisol (diurnal and reactive) and
      general measures of brain WM hyperintensity (WMH) volume, fractional anisotropy
      (gFA), and mean diffusivity (gMD) in 90 males, aged 73 years. Significant
      associations were predominantly found between cortisol measures and WMHs and gMD
      but not gFA. Higher cortisol at the start of a mild cognitive stressor was
      associated with higher WMH and gMD. Higher cortisol at the end was associated
      with greater WMHs. A constant or increasing cortisol level during cognitive
      testing was associated with lower gMD. Tract-specific bases of these associations
      implicated anterior thalamic radiation, uncinate, and arcuate and inferior
      longitudinal fasciculi. The cognitive sequelae of these relationships, above
      other covariates, are a priority for future study.

PMID- 25066241
TI  - Utilising a collective case study system theory mixed methods approach: a rural
      health example.
AB  - BACKGROUND: Insight into local health service provision in rural communities is
      limited in the literature. The dominant workforce focus in the rural health
      literature, while revealing issues of shortage of maldistribution, does not
      describe service provision in rural towns. Similarly aggregation of data tends to
      render local health service provision virtually invisible. This paper describes a
      methodology to explore specific aspects of rural health service provision with an
      initial focus on understanding rurality as it pertains to rural physiotherapy
      service provision. METHOD: A system theory-case study heuristic combined with a
      sequential mixed methods approach to provide a framework for both quantitative
      and qualitative exploration across sites. Stakeholder perspectives were obtained
      through surveys and in depth interviews. The investigation site was a large area
      of one Australian state with a mix of rural, regional and remote communities.
      RESULTS: 39 surveys were received from 11 locations within the investigation site
      and 19 in depth interviews were conducted. Stakeholder perspectives of rurality
      and workforce numbers informed the development of six case types relevant to the
      exploration of rural physiotherapy service provision. Participant perspective of
      rurality often differed with the geographical classification of their location.
      The numbers of onsite colleagues and local access to health services contributed
      to participant perceptions of rurality. CONCLUSIONS: The complexity of
      understanding the concept of rurality was revealed by interview participants when
      providing their perspectives about rural physiotherapy service provision. Dual
      measures, such as rurality and workforce numbers, provide more relevant
      differentiation of sites to explore specific services, such rural physiotherapy
      service provision, than single measure of rurality as defined by geographic
      classification. The system theory-case study heuristic supports both qualitative
      and quantitative exploration in rural health services research.

PMID- 25066242
TI  - Has analytical flexibility increased in imaging studies of bipolar disorder and
      major depression?
AB  - There has been extensive discussion of problems of reproducibility of research.
      Analytical flexibility may contribute to this, by increasing the likelihood that
      a reported finding represents a chance result. We explored whether analytical
      flexibility has increased over time, using human imaging studies of bipolar
      disorder and major depression. Our results indicate that the number of measures
      collected per study has increased over time for studies of bipolar disorder, but
      not for studies of major depression. 

PMID- 25066244
TI  - The Image Gently in Dentistry campaign: promotion of responsible use of
      maxillofacial radiology in dentistry for children.

PMID- 25066245
TI  - Future directions for endovascular management of patients with acute ischemic
      stroke.

PMID- 25066246
TI  - Neurocognitive profiles in help-seeking individuals: comparison of risk for
      psychosis and bipolar disorder criteria.
AB  - BACKGROUND: Neurocognitive deficits are important aspects of the schizophrenic
      disorders because they have a strong impact on social and vocational outcomes. We
      expanded on previous research by focusing on the neurocognitive profiles of
      persons at high risk (HR) or ultra-high risk (UHR) for schizophrenic and
      affective psychoses. Our main aim was to determine whether neurocognitive
      measures are sufficiently sensitive to predict a group affiliation based on
      deficits in functional domains. METHOD: This study included 207 help-seeking
      individuals identified as HR (n = 75), UHR (n = 102) or at high risk for bipolar
      disorder (HRBip; n = 30), who were compared with persons comprising a matched,
      healthy control group (CG; n = 50). Neuropsychological variables were sorted
      according to their load in a factor analysis and were compared among groups. In
      addition, the likelihood of group membership was estimated using logistic
      regression analyses. RESULTS: The performance of HR and HRBip participants was
      comparable, and intermediate between the controls and UHR. The domain of
      processing speed was most sensitive in discriminating HR and UHR [odds ratio (OR)
      0.48, 95% confidence interval (CI) 0.28-0.78, p = 0.004] whereas learning and
      memory deficits predicted a conversion to schizophrenic psychosis (OR 0.47, 95%
      CI 0.25-0.87, p = 0.01). CONCLUSIONS: Performances on neurocognitive tests
      differed among our three at-risk groups and may therefore be useful in predicting
      psychosis. Overall, cognition had a profound effect on the extent of general
      functioning and satisfaction with life for subjects at risk of psychosis. Thus,
      this factor should become a treatment target in itself.

PMID- 25066247
TI  - TIPPing practice away from anticoagulation in pregnancy.

PMID- 25066249
TI  - Phased-array of microcoils allows MR microscopy of ex vivo human skin samples at
      9.4 T.
AB  - PURPOSE: The aim of this study was to demonstrate the feasibility of a custom
      made phased-array microcoil within a 400 MHz animal system for the morphological
      characterization of human skin tissue in correlation with histopathology.
      MATERIALS AND METHODS: A dedicated 7-channel microcoil-based MR detector arranged
      in a phased-array geometry was developed to combine the advantages of both a
      large field of view and a high signal-to-noise ratio. Standard gradient echo
      sequences were adapted for the characterization of skin morphology ex vivo.
      RESULTS: In this study, the feasibility of using this type of microdetector,
      combined with specially manufactured sample holders, to achieve high-resolution
      MR images of fresh and formalin-fixed, normal and hidradenitis suppurativa
      diseased skin was successfully demonstrated. The setup presented in this work
      allows reliable acquisitions of high-resolution images with in-plane resolution
      up to 25 * 25 MUm2, and 100 MUm in the orthogonal direction, thereby allowing the
      differentiation of typical layers of the skin, sebaceous glands and hair
      follicle. CONCLUSION: This study demonstrates that MR microscopy on skin biopsies
      can be applied at low cost on a standard animal MR imaging system. The successful
      imaging of different skin structures ex vivo is a prerequisite for non-invasive,
      in vivo application of skin MR microscopy for accurate complementary disease
      diagnosis in dermatology.

PMID- 25066248
TI  - Antepartum dalteparin versus no antepartum dalteparin for the prevention of
      pregnancy complications in pregnant women with thrombophilia (TIPPS): a
      multinational open-label randomised trial.
AB  - BACKGROUND: Thrombophilias are common disorders that increase the risk of
      pregnancy-associated venous thromboembolism and pregnancy loss and can also
      increase the risk of placenta-mediated pregnancy complications (severe pre
      eclampsia, small-for-gestational-age infants, and placental abruption). We
      postulated that antepartum dalteparin would reduce these complications in
      pregnant women with thrombophilia. METHODS: In this open-label randomised trial
      undertaken in 36 tertiary care centres in five countries, we enrolled consenting
      pregnant women with thrombophilia at increased risk of venous thromboembolism or
      with previous placenta-mediated pregnancy complications. Eligible participants
      were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose
      dalteparin (5000 international units once daily up to 20 weeks' gestation, and
      twice daily thereafter until at least 37 weeks' gestation) or to no antepartum
      dalteparin (control group). Randomisation was done by a web-based randomisation
      system, and was stratified by country and gestational age at randomisation day
      with a permuted block design (block sizes 4 and 8). At randomisation, site
      pharmacists (or delegates) received a randomisation number and treatment
      allocation (by fax and/or e-mail) from the central web randomisation system and
      then dispensed study drug to the local coordinator. Patients and study personnel
      were not masked to treatment assignment, but the outcome adjudicators were
      masked. The primary composite outcome was independently adjudicated severe or
      early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th
      percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat
      and on-treatment analyses. This trial is registered with ClinicalTrials.gov,
      number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504.
      FINDINGS: Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to
      participate and were randomly assigned to the two groups. Three women were
      excluded after randomisation because of ineligibility (two in the antepartum
      dalteparin group and one in the control group), leaving 146 women assigned to
      antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients
      crossed over to the other group during treatment, and therefore for on-treatment
      and safety analysis there were 143 patients in the dalteparin group and 141 in
      the no dalteparin group. Dalteparin did not reduce the incidence of the primary
      composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17.1%;
      95% CI 11.4-24.2%] vs no dalteparin 27/143 [18.9%; 95% CI 12.8-26.3%]; risk
      difference -1.8% [95% CI -10.6% to 7.1%)) and on-treatment analysis (dalteparin
      28/143 [19.6%] vs no dalteparin 24/141 [17.0%]; risk difference +2.6% [95% CI 
      6.4 to 11.6%]). In safety analysis, the occurrence of major bleeding did not
      differ between the two groups. However, minor bleeding was more common in the
      dalteparin group (28/143 [19.6%]) than in the no dalteparin group (13/141 [9.2%];
      risk difference 10.4%, 95% CI 2.3-18.4; p=0.01). INTERPRETATION: Antepartum
      prophylactic dalteparin does not reduce the occurrence of venous thromboembolism,
      pregnancy loss, or placenta-mediated pregnancy complications in pregnant women
      with thrombophilia at high risk of these complications and is associated with an
      increased risk of minor bleeding. FUNDING: Canadian Institutes of Health
      Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.

PMID- 25066250
TI  - Maintenance of bladder innervation in diabetes: a stereological study of
      streptozotocin-treated female rats.
AB  - Neuropathy and cystopathy are two common conditions in patients with chronic
      diabetes. Despite obvious bladder sensory and motor nerve dysfunction in
      diabetes, no studies have selectively explored whether sensory or motor
      innervation is affected in the bladder. In the present study, we tested the
      hypothesis that loss of bladder sensory and motor fibers is responsible for
      bladder sensory and motor dysfunction. Parasympathetic and sensory innervation of
      the bladder dome and neck were examined using immunohistochemistry (IHC) and
      stereology in adult female rats 12weeks after induction of diabetes by
      streptozotocin. Naive and age matched rats were evaluated as controls. Diabetic
      rats had mean blood glucose level of >400mg/dl, and bladder weights and
      thicknesses that were more than doubled compared to naive rats. In naive rats,
      parasympathetic vesicular acetylcholine transporter (VAT) and sensory calcitonin
      gene-related peptide (CGRP) immunopositive nerve fibers were located in bladder
      smooth muscle and were more densely distributed in the neck compared to the dome.
      Within the urothelial region, CGRP nerve fibers were densely distributed while
      VAT nerve fibers were sparsely distributed in the bladder neck and both were
      virtually absent in the bladder dome. Streptozotocin induced diabetes did not
      change the total nerve fiber length of either VAT or CGRP stained fibers in
      either the neck or dome. These studies indicate that hyperglycemia, induced by
      streptozotocin treatment, does not result in a loss of parasympathetic VAT or
      CGRP sensory nerve fibers, per se, but the doubling of bladder weight and mass
      does indicate a decrease in innervation density. 

PMID- 25066251
TI  - Health-Related Quality of Life Among Cancer Survivors Attending Support Groups.
AB  - There is limited research on the relationship between Health-related quality of
      life (HRQoL) and socioeconomic status (SES) among long-term cancer survivors. The
      goal of this study was to assess Global HRQoL among 102 adult cancer survivors
      attending support groups in San Diego County and to examine differences by SES
      and acculturation. Community-based participatory research methods were followed
      to recruit a purposive sample of English and Spanish-speaking adult cancer
      survivors attending cancer support groups. Self-report questionnaires assessing
      age, acculturation (i.e., language), SES (i.e., income and education), cancer
      history, and Global HRQoL measured by the FACT-G were administered. Multivariate
      regression examined the relationship between SES and acculturation with HRQoL,
      adjusting for covariates. Participants were 58.8 years on average (SD = 10.06)
      and varied in terms of SES. Most participants (91.5 %) were women, 51.7 % were
      non-Hispanic white, and 48.3 % were Hispanic/Latino. Global HRQoL scores in the
      study sample were lower compared to previously reported studies. After adjusting
      for covariates, SES and acculturation were not significantly related to HRQoL.
      Stage at diagnosis was significantly related to HRQoL measures in adjusted
      analyses. HRQoL did not vary by SES or acculturation. There is a need to increase
      access to linguistically and culturally appropriate cancer care and supportive
      care services. Future studies may find existing support group settings useful for
      targeting psychosocial issues for more advanced stage cancer survivors.

PMID- 25066252
TI  - Sociodemographic and environmental correlates of active commuting in rural
      America.
AB  - PURPOSE: This research investigated participation rates in 3 modes of active
      commuting (AC) and their sociodemographic and physical environmental correlates
      in rural America. METHODS: The 2000 Census supplemented with other data sets were
      used to analyze AC rates in percentage of workers walking, biking, and taking
      public transportation to work in 14,209 nonmetropolitan rural tracts identified
      by RUCA codes, including 4,067 small rural and 10,142 town-micropolitan rural
      tracts. Sociodemographic and physical environmental variables were correlated
      with 3 AC modes simultaneously using Seemingly Unrelated Regression for nonmetro
      rural, and for small rural and town-micropolitan rural separately. FINDINGS: The
      average AC rates in rural tracts were 3.63%, 0.26%, and 0.56% for walking,
      biking, and public transportation to work, respectively, with small rural tracts
      having a higher rate of walking but lower rates of biking and public
      transportation to work than town-micropolitan tracts. In general, better economic
      well-being was negatively associated with AC but percentage of college-educated
      was a positive correlate. Population density was positively associated with AC
      but greenness and proximity to parks were negative correlates. However,
      significant differences existed for different AC modes, and between small rural
      and town-micropolitan rural tracts. CONCLUSIONS: Sociodemographic factors
      explained more variance in AC than physical environmental factors but the
      detailed relationships were complex, varying by AC mode and by degree of
      rurality. Any strategy to promote AC in rural America needs to be sensitive to
      the population size of the area and assessed in a comprehensive manner to avoid a
      "one size fits all" approach.

PMID- 25066253
TI  - [18F]fluorothymidine-positron emission tomography in patients with locally
      advanced breast cancer under bevacizumab treatment: usefulness of different
      quantitative methods of tumor proliferation.
AB  - OBJECTIVES: To investigate quantitative methods of tumor proliferation using 3'
      [(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer
      (BC), studied before and after one bevacizumab administration, and to correlate
      the [(18)F]FLT-PET uptake with the Ki67 index. MATERIAL AND METHODS: Thirty
      patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and
      14 days after bevacizumab treatment. A dynamic scan centered over the tumor began
      simultaneously with the injection of [(18)F]FLT (385 +/- 56 MBq). Image derived
      input functions were obtained using regions of interest drawn on the left
      ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were
      used as input functions to obtain the kinetic Ki constant using the Patlak
      graphical analysis (time interval 10-60 min after injection). Maximum SUV values
      were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET
      parameters were correlated with the Ki67 index obtained staining tumor biopsies.
      RESULTS: [(18)F]FLT uptake parameters decreased significantly (p<0.001) after
      treatment: SUV50=3.09 +/- 1.21 vs 2.22 +/- 0.96; SUV40=3.00 +/- 1.18 vs 2.14 +/-
      0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11
      98]. Consistency interclass correlation coefficients within SUV and within Ki
      were high. Changes of SUV50 and Ki_DA between baseline PET and after one
      bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and
      0.26, p=0.06 and 0.16, respectively). CONCLUSIONS: [(18)F]FLT-PET is useful to
      demonstrate proliferative changes after a dose of bevacizumab in patients with
      BC. Quantification of tumor proliferation by means of SUV and Ki has shown
      similar results, but SUV50 obtained better results. A correlation between
      [(18)F]FLT changes and Ki67 index was observed.

PMID- 25066254
TI  - Novel RNA recognition motif domain in the cytoplasmic polyadenylation element
      binding protein 3.
AB  - The family of cytoplasmic polyadenylation element binding proteins CPEB1, CPEB2,
      CPEB3, and CPEB4 binds to the 3'-untranslated region (3'-UTR) of mRNA, and plays
      significant roles in mRNA metabolism and translation regulation. They have a
      common domain organization, involving two consecutive RNA recognition motif (RRM)
      domains followed by a zinc finger domain in the C-terminal region. We solved the
      solution structure of the first RRM domain (RRM1) of human CPEB3, which revealed
      that CPEB3 RRM1 exhibits structural features distinct from those of the canonical
      RRM domain. Our structural data provide important information about the RNA
      binding ability of CPEB3 RRM1.

PMID- 25066255
TI  - Dietary sweet potato (Ipomoea batatas L.) leaf extract attenuates hyperglycaemia
      by enhancing the secretion of glucagon-like peptide-1 (GLP-1).
AB  - 'Suioh', a sweet potato (Ipomoea batatas L.) cultivar developed in Japan, has
      edible leaves and stems. The sweet potato leaves contain polyphenols such as
      caffeoylquinic acid (CQA) derivatives. It has multiple biological functions and
      may help to regulate the blood glucose concentration. In this study, we first
      examined whether sweet potato leaf extract powder (SP) attenuated hyperglycaemia
      in type 2 diabetic mice. Administration of dietary SP for 5 weeks significantly
      lowered glycaemia in type 2 diabetic mice. Second, we conducted in vitro
      experiments, and found that SP and CQA derivatives significantly enhanced
      glucagon-like peptide-1 (GLP-1) secretion. Third, pre-administration of SP
      significantly stimulated GLP-1 secretion and was accompanied by enhanced insulin
      secretion in rats, which resulted in a reduced glycaemic response after glucose
      injection. These results indicate that oral SP attenuates postprandial
      hyperglycaemia, possibly through enhancement of GLP-1 secretion. 

PMID- 25066256
TI  - Ultrafast electron injection at the cationic porphyrin-graphene interface
      assisted by molecular flattening.
AB  - The steady-state and femtosecond (fs) time-resolved data clearly demonstrate that
      the charge transfer (CT) process at the porphyrin-graphene carboxylate (GC)
      interfaces can be tuned from zero to very sufficient and ultrafast by changing
      the electronic structure of the meso unit and the redox properties of the
      porphyrin cavity. 

PMID- 25066257
TI  - Most appropriate animal models to study the efficacy of statins: a systematic
      review.
AB  - BACKGROUND: In animal models and clinical trials, statins are reported as
      effective in reducing cholesterol levels and lowering the risk of cardiovascular
      diseases. We have aggregated the findings in animal models - mice, rats and
      rabbits - using the technique of systematic review and meta-analysis to highlight
      differences in the efficacy of statins. MATERIALS AND METHODS: We searched
      Medline and Embase. After examining all eligible articles, we extracted results
      about total cholesterol and other blood parameters, blood pressure, myocardial
      infarction and survival. Weighted and standard mean difference random effects
      meta-analysis was used to measure overall efficacy in prespecified species,
      strains and subgroups. RESULTS: We included in systematic review 161 animal
      studies and we analysed 120 studies, accounting for 2432 animals. Statins lowered
      the total cholesterol across all species, although with large differences in the
      effect size: -30% in rabbits, -20% in mice and -10% in rats. The reduction was
      larger in animals fed on a high-cholesterol diet. Statins reduced infarct volume
      but did not consistently reduce the blood pressure or effect the overall
      survival. Few studies considered strains at high risk of cardiovascular diseases
      or hard outcomes. CONCLUSIONS: Although statins showed substantial efficacy in
      animal models, few preclinical data considered conditions mimicking human
      pathologies for which the drugs are clinically indicated and utilized. The
      empirical finding that statins are more effective in lowering cholesterol derived
      from an external source (i.e. diet) conflicts with statin's supposed primary
      mechanism of action.

PMID- 25066258
TI  - Solid-phase assays for the detection of alloantibody against human leukocyte
      antigens: panacea or Pandora?
AB  - Serological assessments of antibodies directed against human leucocyte antigens
      (HLA) formed the basis of early histocompatibility testing (Patel & Terasaki,
      1969 N Engl J Med, 280, 735). However, over the past decade, significant advances
      in HLA antibody detection technologies have emerged. The development and
      implementation of solid-phase assays has led to safer and more efficient
      allocation of organs by effectively distinguishing HLA from non-HLA antibodies.
      Although solid-phase assays are not standardized, they are widely accepted as the
      new 'gold standard'. However, this technology is not without its challenges. This
      review is intended to provide a better understanding of solid-phase HLA antibody
      testing and will focus on important caveats associated with this evolving
      technology. Examples of the limitations of the technology as well as common data
      misinterpretations will be shown. Both of which could pose potential harm to
      transplant recipients (Tait et al., Transplantation, 95, 19). 

PMID- 25066259
TI  - Retinitis pigmentosa and macular degeneration in a patient with ataxia with
      isolated vitamin E deficiency with a novel c.717 del C mutation in the TTPA gene.
AB  - Ataxia with isolated vitamin E deficiency (AVED) is a neurodegenerative disease
      caused by a mutation in the alpha-tocopherol transfer protein gene (TTPA). The
      clinical features of the disease resemble Friedreich's ataxia. However, AVED is
      associated with low plasma vitamin E levels, which results in compromised
      antioxidant function. Dysregulation of this lipid-soluble antioxidant vitamin
      plays a major role in the neurodegeneration observed in AVED. Some AVED patients
      experience decreased visual acuity. Retinitis pigmentosa is thought to be the
      main cause of this visual impairment. Although antioxidant levels are important
      for the prevention of macular degeneration, there have been no reports of macular
      degeneration in AVED. Here, we describe a patient with AVED with progressive
      macular degeneration, who carried a novel truncating mutation-c.717 del C
      (p.D239EfsX25)-in exon 5 of the TTPA gene. These findings suggest that this newly
      identified mutation results in severely low serum vitamin E levels, which may be
      associated with the development of retinitis pigmentosa and macular degeneration.

PMID- 25066260
TI  - Functional polymorphisms of the MAO gene with Parkinson disease susceptibility: a
      meta-analysis.
AB  - OBJECTIVE: We carried out a meta-analysis focusing on the relationships between
      rs1137070 C>T and rs1799836 A>G polymorphisms in the MAO gene as a modifier of
      Parkinson disease (PD) susceptibility. METHOD: A literature search of the
      Cochrane Library Database, Web of Science, PubMed, CINAHL, EMBASE, and the
      Chinese Biomedical Database (CBM) was performed without any language restrictions
      on articles published before April 10st, 2014. We choose the STATA 12.0
      statistical software to deal with statistical data. Crude odds ratios (ORs)
      estimates with 95% confidence interval (95% CI) were also provided. RESULTS:
      Fourteen independent case-control studies met our predetermined inclusion
      criteria and were included in the meta-analysis. Two major polymorphisms
      rs1137070 C>T and rs1799836 A>G in the MAO gene were performed in this meta
      analysis. When all the eligible studies were pooled into the meta-analysis, our
      results indicated that rs1137070 C>T polymorphism and rs1799836 A>G polymorphism
      have statistically significant correlation with the increased risk of PD in the
      majority groups. Ethnicity-stratified analysis revealed a relation between the
      rs1137070 C>T polymorphism and PD risk among Asians and Caucasians in the
      majority groups. Additionally, there was an apparent association between the
      rs1799836 A>G variant and PD risk among the Asian populations under 4 genetic
      models (G allele vs. A allele: OR=0.84, 95% CI=0.72-0.97, P=0.021; GG vs. AA+AG:
      OR=1.73, 95% CI=1.25-2.39, P=0.001; GG vs. AA: OR=1.56, 95% CI=1.18-2.04,
      P=0.002; GG vs. AG: OR=3.42, 95% CI=1.86-6.30, P<0.001; respectively).
      CONCLUSION: The relationships in the polymorphisms of rs1137070 C>T and rs1799836
      A>G in the MAO gene with PD susceptibility observed in our meta-analyses support
      the view that the MAO gene may play an important role in the development of PD.

PMID- 25066261
TI  - A pitfall of brain MRI in evaluation of numb chin syndrome: mandibular MRI should
      be included to localize lesions.

PMID- 25066262
TI  - Molecular, phenotypic and pathogenic variability in Colletotrichum isolates of
      subtropical region in north-eastern India, causing fruit rot of chillies.
AB  - AIM: To study the genetic variability and population structure of Colletotrichum
      species found to be associated with anthracnose of chilli in the north-eastern
      region of India. METHODS AND RESULTS: Twenty-three Colletotrichum isolates were
      obtained from infected chilli fruits and leaves from the chilli growing regions
      of north-eastern Uttar Pradesh, India, identified as Colletotrichum capsici and
      Colletotrichum acutatum using species-specific primers. Genetic variability among
      the isolates was analysed using RAPD and ISSR markers. The RAPD marker
      efficiently grouped the isolates at species level, while ISSR marker was
      effective in separating the isolates based on geographical origin. In vitro
      pathogenic test revealed the inability of C. acutatum isolates to infect unripe
      fruits, while C. capsici isolates were found to infect both ripe and unripe
      fruits at disease severity scale 7-9. Growth rate on different media was recorded
      to cross-confirm the classification of isolates, which clearly grouped the two
      species into distinct group on PCA plot. CONCLUSIONS: Two species, viz. C.
      capsici and C. acutatum, prevalent in the region were found to infect the fruits
      at postripening stage. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study
      proposes the implementation of management strategies at postripening stages of
      the crop to control the spread of disease, thereby leading to increment in
      production of chilli in the given region.

PMID- 25066264
TI  - Progress in base-metal water oxidation catalysis.
AB  - This minireview provides a brief overview of the progress that has been made in
      developing homogeneous water oxidation catalysts based on base metals (manganese,
      iron, cobalt, nickel, and copper) from the 1990s to mid-2014. The impact of each
      contribution is analyzed, and opportunities for further improvement are noted. In
      addition, the relative stabilities of the base-metal catalysts that have been
      reported are compared to illustrate the importance of developing more robust
      catalytic systems by using these metals. This manuscript is intended to provide a
      firm foundation for researchers entering the field of water oxidation based on
      base metals and a useful reference for those currently involved in the field. 

PMID- 25066263
TI  - Deslorelin for the treatment of hair cycle arrest in intact male dogs.
AB  - BACKGROUND: Hair cycle arrest (alopecia X) refers to a canine alopecic condition
      of unknown pathogenesis, characterized by symmetrical, nonpruritic and
      noninflammatory alopecia that spares the head and distal extremities.
      HYPOTHESIS/OBJECTIVES: The objective of this study was prospectively to evaluate
      the efficacy of a 4.7 mg deslorelin implant in the treatment of intact male and
      neutered female dogs affected by hair cycle arrest. ANIMALS: Ten Pomeranian dogs
      (eight intact males, two neutered females), four Italian spitz (three intact
      males, one neutered female), three miniature poodles (two intact males, one
      neutered female), two Siberian huskies (both intact males) and one intact male
      chow chow dog with confirmed hair cycle arrest were included in the study.
      METHODS: Each dog was treated with a subcutaneous sterile implant containing 4.7
      mg deslorelin. Responder dogs were re-implanted 6 months after the first implant
      in order to obtain a 1 year pharmacological exposure and 1 year of follow-up.
      RESULTS: Hair regrowth was visible within 3 months in 12 of 16 intact male dogs
      (75%); no hair regrowth was noted in any neutered female dogs. The overall
      response to therapy was 60%. No adverse effects were noted. CONCLUSIONS AND
      CLINICAL IMPORTANCE: These findings suggest that deslorelin may be a treatment
      option for intact male dogs with idiopathic hair cycle arrest. Deslorelin is an
      alternative to current therapies and castration.

PMID- 25066265
TI  - The hypotensive effect of the ruthenium complex [Ru(terpy)(bdq)NO]3+ is higher in
      male than in female spontaneously hypertensive rats (SHR).
AB  - We have previously demonstrated that the hypotensive effect of the ruthenium
      complex [Ru(terpy)(bdq)NO](3+) (TERPY) is slow, long lasting, and does not lead
      to reflex tachycardia. TERPY's hypotensive effect is increased in hypertensive
      rats (SHR or 2 kidney-1clip) compared with normotensive rats. We hypothesized
      that sexual differences could interfere in the hypotensive effects of nitric
      oxide (NO) donors in SHR. Therefore, here we aimed to investigate the role of
      sexual differences and endogenous NO in the hypotension induced by TERPY. In
      conscious, unrestrained animals, we evaluated the hypotensive effect of TERPY
      before and after the administration of N-nitro-L-arginine methyl ester (L-NAME)
      (nonselective NO synthase inhibitor), APOCYNIN (NADPH/NOX inhibitor), and TEMPOL
      (superoxide dismutase mimetic). The hypotensive effect of TERPY was higher in
      male than in female SHR, but this difference was not observed in the normotensive
      Wistar group. The effect of TERPY increased after administration of L-NAME in
      Wistar rats; however, this effect was not altered by L-NAME in SHR. In SHR,
      sexual dimorphism in TERPY effect was still observed in animals treated with L
      NAME. TEMPOL increases the effect of TERPY only in female SHR. After TEMPOL, the
      sexual dimorphism in TERPY effect was abolished in the SHR group. APOCYNIN
      increased the effect of TERPY in male and female Wistar and SHR, but maintained
      the previously observed difference between male and female SHR. Thus, this study
      shows that TERPY's hypotensive effect increased in male compared with female SHR
      and indicates that sexual dimorphism in TERPY effect is associated with oxidative
      stress.

PMID- 25066267
TI  - Set-shifting ability across the spectrum of eating disorders and in overweight
      and obesity: a systematic review and meta-analysis.
AB  - BACKGROUND: In this meta-analysis we review the findings from neuropsychological
      studies on set-shifting in people with eating disorders (EDs) or
      overweight/obesity. METHOD: Four databases (PubMed, PsycINFO, PSYNDEX and Web of
      Science) were searched for eligible studies. Effect sizes (ESs) were pooled using
      random-effects models. Moderator analyses were conducted for ED and
      overweight/obese subgroups, adult/adolescent samples and measures of set
      shifting. RESULTS: Sixty-four studies with a total of 1825 ED patients [1394
      anorexia nervosa (AN), 376 bulimia nervosa (BN) and 55 binge eating disorder
      (BED)] and 10 studies with a total of 449 overweight/obese individuals were
      included. The meta-analysis revealed a small to medium ES for inefficient set
      shifting across all three ED diagnoses (Hedges' g = -0.45). Subgroup analyses
      yielded small to medium ESs for each ED subtype (g = -0.44 for AN, -0.53 for BED,
      -0.50 for BN), which did not differ significantly. There was a medium ES for
      restricting type AN (ANR; g = -0.51) but no significant ES for binge/purge type
      AN (AN/BP; g = -0.18). A medium ES was found across obesity studies (g = -0.61).
      The ES across overweight studies was not significant (g = -0.07). Adult samples
      did not differ from adolescent samples in either ED or overweight/obesity
      studies. The different set-shifting measures were associated with largely varying
      ESs. CONCLUSIONS: The meta-analysis provides strong support that inefficient set
      shifting is a salient neuropsychological phenomenon across ED subtypes and
      obesity, but is less prominent in AN/BP and overweight. Compulsivity seems to be
      a common underlying factor supporting a dimensional and transdiagnostic
      conceptualization of EDs and obesity.

PMID- 25066266
TI  - Neuropsychological deficits in past suicide attempters with varying levels of
      depression severity.
AB  - BACKGROUND: Our previous work identified deficits in interference processing and
      learning/memory in past suicide attempters who were currently depressed and
      medication-free. In this study, we extend this work to an independent sample
      studied at various stages of illness and treatment (mild symptoms, on average) to
      determine if these deficits in past suicide attempters are evident during a less
      severe clinical state. METHOD: A total of 80 individuals with a past history of
      major depression and suicide attempt were compared with 81 individuals with a
      history of major depression and no lifetime suicide attempts on a battery of
      neurocognitive measures assessing attention, memory, abstract/contingent
      learning, working memory, language fluency and impulse control. RESULTS: Past
      attempters performed more poorly in attention, memory and working memory domains,
      but also in an estimate of pre-morbid intelligence. After correction for this
      estimate, tests that had previously distinguished past attempters - a
      computerized Stroop task and the Buschke Selective Reminding Test - remained
      significantly worse in attempters. In a secondary analysis, similar differences
      were found among those with the lowest levels of depression (Hamilton Depression
      Rating Scale score <10), suggesting that these deficits may be trait markers
      independent of current symptomatology. CONCLUSIONS: Deficits in interference
      processing and learning/memory constitute an enduring defect in information
      processing that may contribute to poor adaptation, other higher-order cognitive
      impairments and risk for suicidal behavior.

PMID- 25066268
TI  - Fecal volatile organic compounds: a novel, cheaper method of diagnosing
      inflammatory bowel disease?
AB  - The investigation of a novel, cheaper method of diagnosing inflammatory bowel
      disease (IBD) is an area of active research. Recently, investigations into the
      metabolomic profile of IBD patients and animal models of colitis compared to
      healthy controls has begun to receive considerable attention and correlations
      between the fecal volatile organic compound (VOC) metabolome and IBD is merging.
      Patients and clinicians have often reported a change in odor of feces during
      relapse of IBD. Therefore, this article will focus specifically on the fecal VOC
      metabolome and its potential role in identifying a novel diagnostic method for
      IBD. 

PMID- 25066270
TI  - Global protein profiling studies of chikungunya virus infection identify
      different proteins but common biological processes.
AB  - Chikungunya fever (CHIKF) caused by the mosquito-transmitted chikungunya virus
      (CHIKV) swept into international prominence from late 2005 as an epidemic of
      CHIKF spread around countries surrounding the Indian Ocean. Although significant
      advances have been made in understanding the pathobiology of CHIKF, numerous
      questions still remain. In the absence of commercially available specific drugs
      to treat the disease, or a vaccine to prevent the diseases, the questions have
      particular significance. A number of studies have used global proteome analysis
      to increase our understanding of the process of CHIKV infection using a number of
      different experimental techniques and experimental systems. In all, over 700
      proteins have been identified in nine different analyses by five different groups
      as being differentially regulated. Remarkably, only a single protein, eukaryotic
      elongation factor 2, has been identified by more than two different groups as
      being differentially regulated during CHIKV infection. This review provides a
      critical overview of the studies that have used global protein profiling to
      understand CHIKV infection and shows that while a broad consensus is emerging on
      which biological processes are altered during CHIKV infection, this consensus is
      poorly supported in terms of consistent identification of any key proteins
      mediating those biological processes.

PMID- 25066269
TI  - Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or
      bevacizumab for metastatic colorectal cancer.
AB  - BACKGROUND: Although CRC is the third most commonly diagnosed cancer in the
      United States, second-line CRC treatment is limited. In this trial we examined
      the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase
      inhibitor of vascular endothelial growth factor and platelet-derived growth
      factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6,
      in previously treated metastatic CRC. PATIENTS AND METHODS: One hundred forty
      eight patients with advanced CRC previously treated with fluoropyrimidine or
      irinotecan received bevacizumab (10 mg/kg, intravenous), low-dose linifanib (7.5
      mg), or high-dose linifanib (12.5 mg), with mFOLFOX6. The primary end point was
      progression-free survival (PFS). Secondary objectives included overall survival
      (OS), objective response rate (ORR), and safety. RESULTS: No statistically
      significant differences in PFS occurred between bevacizumab and linifanib doses
      (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.830-2.539]; high,
      HR, 1.257 [95% CI, 0.672-2.351]). Median OS values were similar for bevacizumab
      and high-dose linifanib (bevacizumab, 16.5 months [95% CI, 13.0-not available];
      high-dose linifanib, 16.4 months [95% CI, 11.9-21.7]; low-dose linifanib, 12.0
      months [95% CI, 10.1-13.0]). ORRs were similar (bevacizumab, 34.7% [95% CI, 21.7
      49.6]; low-dose linifanib, 24.0% [95% CI, 13.1-38.2]; high-dose linifanib, 22.4%
      [95% CI, 11.8-36.6]). Median cycles of 5-fluorouracil were reduced in the
      linifanib arms, versus the bevacizumab arm. Grade 3/4 adverse event occurrences
      were more frequent with linifanib. Palmar-plantar erythrodysesthesia,
      hypothyroidism, and thrombocytopenia were more common with high-dose linifanib
      than bevacizumab. CONCLUSION: Combining linifanib with mFOLFOX6 as a second-line
      treatment for metastatic CRC did not improve PFS, radiographic findings, or
      duration of response versus bevacizumab and mFOLFOX6.

PMID- 25066271
TI  - Lifespan regulation under axenic dietary restriction: a close look at the usual
      suspects.
AB  - In Caenorhabditis elegans, there are several ways to impose dietary restriction
      (DR) all of which extend lifespan to a different degree. Until recently, the
      molecular mechanisms underlying the DR-mediated lifespan extension were
      completely unknown but extensive efforts led to the identification of several key
      players in this process. Culture in sterile axenic medium is a method of DR
      (ADR), leading to an impressive doubling of lifespan. Earlier, we established
      that ADR-mediated longevity is independent of Ins/IGF signaling and eat-2. The
      only gene reported to be indispensable for the ADR lifespan effect is cbp-1
      (Zhang et al., 2009) which was confirmed in this study. In an attempt to identify
      more genes involved in ADR-mediated longevity, we tested several candidate genes
      known to regulate lifespan extension in other DR regimens. We found that cup-4 is
      equally important as cbp-1 in ADR-mediated longevity and we identified some genes
      that may contribute to ADR-induced longevity, but are not required for the full
      lifespan effect. 

PMID- 25066272
TI  - Maternal filicide in Turkey.
AB  - Filicide occurs in every socioeconomic stratum around the world. This study was
      conducted to evaluate motives, psychopathological aspects, and socio-demographic
      factors of 74 filicide cases of women in Turkey. Mean age of mothers, most of
      whom committed infanticide, was 26 years, and breakdown of criminal offenses are
      as follows: "to get rid of unwanted babies" (24.3%), "acute psychotic-type
      filicide" (21.6%), "fatal child abuse and neglect" (17.6%), "to get revenge"
      (12.2%), "protect the lonely child from the harm and badness after suicide"
      (10.8%), and "pity" (9.5%) motives. Results showed that maternal filicide cannot
      be reduced to only mental instability or environmental factors and indicates
      deficiencies in the capacity of the mothers' role in connecting with their child
      and with parenting skills. Finally, with regard to defendants' motives, similar
      factors that contribute to committing maternal filicide should be considered
      while making an assessment of the data and determining employee risk groups.

PMID- 25066273
TI  - Transcription factor Elk-1 participates in the interleukin-1beta-dependent
      regulation of expression of immediate early response gene 3 (IER3).
AB  - Immediate early response gene 3 (IER3) encodes a protein involved in the
      regulation of apoptosis and differentiation. Recently the role of IER3 in the
      regulation of extracellular signal-regulated kinases (ERKs) was discovered. IER3
      prolongs ERKs activation by inhibition of phosphatase PP2A. Here we show that
      interleukin-1beta (IL-1beta)-induced IER3 expression is mediated by the ERK1/2
      target, transcription factor Elk-1. We identified sequences in the IER3 promoter
      responsible for its ERKs-dependent activation, namely ETS5/6. Elk-1 binds to
      these sequences and is phosphorylated following IL-1beta stimulation. Mutation of
      ETS5/6 binding site abolishes activation of IER3 promoter by IL-1beta as well as
      by the constitutively active form of Elk-1 (Elk-VP16). Thus IER3 acts not only as
      a regulator of ERKs activation, but also as a ERKs-Elk-1-dependent downstream
      effector. 

PMID- 25066275
TI  - Replication of genomewide associations with allergic sensitization and allergic
      rhinitis.
AB  - BACKGROUND: Three genomewide metastudies have recently reported associations with
      self-reported allergic rhinitis and allergic sensitization. The three studies
      together identified a set of 37 loci but showed low concordance. This study
      investigates the reproducibility of the detected single nucleotide polymorphism
      (SNP) associations in an extensively characterized longitudinal cohort, BAMSE.
      METHODS: Phenotypic evaluation of allergic rhinitis (AR) and allergic
      sensitization was performed on 2153 children from BAMSE at 8 and 16 years of age.
      Allele frequencies of 39 SNPs were investigated for association with the exact
      allergic phenotypes of the metastudies. Odds ratios and false discovery rates
      were calculated, and the impact of asthma was evaluated. The cases were also
      evaluated for age at onset effects (<= or >8 years of age). RESULTS: Association
      tests of the 39 SNPs identified 12 SNPs with P-values < 0.05 and Q-values < 0.10.
      Two of the four loci (TLR6-TLR1 and HLA-DQA1-HLA-DQB1) identified in all three
      original studies were also identified in this study. Three SNPs located in the
      TLR6-TLR1 locus had the lowest P-values and Q-values < 0.1 when using a well
      defined AR phenotype. Two loci showed significant age at onset effects, but the
      effect of asthma on the associations was very limited. CONCLUSION: The TLR6-TLR1
      locus is likely to have a central role in the development of allergic disease.
      The association between genetic variation in the SSTR1-MIPOL1 and TSLP-SLC25A46
      loci and age at onset is the first report of age at onset effects in allergic
      rhinitis.

PMID- 25066274
TI  - Multi-parametric MRI characterization of healthy human thigh muscles at 3.0 T -
      relaxation, magnetization transfer, fat/water, and diffusion tensor imaging.
AB  - Muscle diseases commonly have clinical presentations of inflammation, fat
      infiltration, fibrosis, and atrophy. However, the results of existing laboratory
      tests and clinical presentations are not well correlated. Advanced quantitative
      MRI techniques may allow the assessment of myo-pathological changes in a
      sensitive and objective manner. To progress towards this goal, an array of
      quantitative MRI protocols was implemented for human thigh muscles; their
      reproducibility was assessed; and the statistical relationships among parameters
      were determined. These quantitative methods included fat/water imaging, multiple
      spin-echo T2 imaging (with and without fat signal suppression, FS), selective
      inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging
      (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T
      from nine healthy subjects. To assess the repeatability of each method, the
      subjects were re-imaged an average of 35 days later. Pre-testing lifestyle
      restrictions were applied to standardize physiological conditions across scans.
      Strong between-day intra-class correlations were observed in all quantitative
      indices except for the macromolecular-to-free water pool size ratio (PSR) with
      FS, a metric derived from qMT data. Two-way analysis of variance revealed no
      significant between-day differences in the mean values for any parameter
      estimate. The repeatability was further assessed with Bland-Altman plots, and low
      repeatability coefficients were obtained for all parameters. Among-muscle
      differences in the quantitative MRI indices and inter-class correlations among
      the parameters were identified. There were inverse relationships between
      fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and
      the standard deviation of the first eigenvector. The FA was positively related to
      the PSR, while the other diffusion indices were inversely related to the PSR.
      These findings support the use of these T1 , T2 , fat/water, and DTI protocols
      for characterizing skeletal muscle using MRI. Moreover, the data support the
      existence of a common biophysical mechanism, water content, as a source of
      variation in these parameters.

PMID- 25066277
TI  - Influenza A/B virus detection and influenza A virus subtyping with emphasis on
      the novel H7N9 virus by using multiplex real-time RT-PCR.
AB  - Infections of the novel avian influenza A H7N9 virus cause severe respiratory
      diseases and death. In this study, to develop highly sensitive methods for
      differentially detecting the H7N9 virus, multiplex and singular real-time reverse
      transcription polymerase chain reaction (RT-PCR) assays were established and
      examined by targeting the H7 and N9 genes of the H7N9 virus. Furthermore, an
      additional multiplex assay combining previous real time RT-PCR designs was
      established to subtype the pandemic H1N1, H3, and H5 influenza viruses. Applying
      the proposed assay system to analyze 100 clinical specimens collected from
      respiratory infection cases identified influenza A viruses (pandemic H1N1 and H3)
      in 23 samples. It has been demonstrated that other common respiratory viruses
      will not be detected by using this platform. 

PMID- 25066276
TI  - Development and clinical testing of a simple, low-density gel element array for
      influenza identification, subtyping, and H275Y detection.
AB  - The objectives of this study were to develop a user-friendly, gel element
      microarray test for influenza virus detection, subtyping, and neuraminidase
      inhibitor resistance detection, assess the performance characteristics of the
      assay, and perform a clinical evaluation on retrospective nasopharyngeal swab
      specimens. A streamlined microarray workflow enabled a single user to run up to
      24 tests in an 8h shift. The most sensitive components of the test were the
      primers and probes targeting the A/H1 pdm09 HA gene with an analytical limit of
      detection (LoD) <100 gene copies (gc) per reaction. LoDs for all targets in
      nasopharyngeal swab samples were <=1000 gc, with the exception of one target in
      the seasonal A/H1N1 subtype. Seasonal H275Y variants were detectable in a mixed
      population when present at >5% with wild type virus, while the 2009 pandemic H1N1
      H275Y variant was detectable at <=1% in a mixture with pandemic wild type virus.
      Influenza typing and subtyping results concurred with those obtained with real
      time RT-PCR assays on more than 97% of the samples tested. The results
      demonstrate that a large panel of single-plex, real-time RT-PCR tests can be
      translated to an easy-to-use, sensitive, and specific microarray test for
      potential diagnostic use.

PMID- 25066278
TI  - Real-time qPCR is a powerful assay to estimate the 171 R/Q alleles at the PrP
      locus directly in a flock's raw milk: a comparison with the targeted next
      generation sequencing.
AB  - The hazard to human health represented by transmissible spongiform
      encephalopathies in sheep is one of the major reasons for implementing the
      genetic selection plan to break down prion diseases. The problem is particularly
      important because of the risk of disease transmission from ewe to lamb via milk
      or colostrum. In order to establish an active and convenient monitoring of the
      flocks already undergone genetic selection and thus, indirectly increase
      consumers' security, the challenge of the work was quantifying the classical
      scrapie risk in bulk milk. A new quantitative real-time PCR assay for the
      estimation of the 171 R and Q allelic frequencies in a DNA pool representative of
      all the lactating ewes present in a flock was optimized and validated "in field".
      The repeatability range was 3.69-5.27 for R and 4.20-5.75 for Q. The ruggedness
      of the allele frequencies resulted 4.26 for R and 4.77 for Q. Regarding the
      validation "in field", none of the considered sources of variability (flock,
      month, number of genotyped animals and somatic cell count) showed a significant
      effect on flock and milk at the linear model. The targeted next-generation
      sequencing was also tested to evaluate its applicability in this context. Results
      show that the real-time PCR assay could represent a valid tool for the
      determination of 171 R/Q allele frequencies in bulk milk. The implementation of a
      service for breeder self-control along the production chain would aim to increase
      the production of high-security dairy products, while monitoring over time of the
      effects of genetic selection in the flocks. 

PMID- 25066279
TI  - Secretory expression of Porcine Circovirus Type 2 capsid protein in Pichia
      pastoris.
AB  - Porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic
      wasting syndrome (PMWS). The PCV2 capsid (Cap) protein is a leading antigen
      candidate for vaccine and serological diagnostic testing, due to its immunogenic
      properties. In this study, the codon-optimized PCV2 Cap gene was cloned into a
      pPICZalphaA vector for secretory expression in the methylotrophic yeast Pichia
      pastoris after methanol induction. The screening of recombinant yeasts was
      followed by detection of the recombinant Cap (rCap) protein by Western blot,
      using sera from pigs naturally infected with PCV2. The rCap secreted protein was
      used without prior purification as a coating antigen in the ELISA test, with high
      discrimination between PCV2-positive and negative sera. These results reveal a
      high confidence in the specific immunoreactivity of the secreted antigen and show
      the antigenicity of the recombinant protein. The feasibility of the P. pastoris
      expression system for the production of PCV2 Cap as secreted protein and its
      apparent bioactivity, suggests there are good prospects for the use of this
      antigen in the investigation of PCV2 infections and testing for vaccine purposes.

PMID- 25066280
TI  - Direct typing of human enteroviruses from wastewater samples.
AB  - A RT-PCR approach for the direct detection and typing of human enteroviruses in
      the environment is described in this study. A semi-nested RT-PCR using COnsensus
      DEgenerated Hybrid Oligonucleotide Primers (CODEHOP) designed from the VP2 genome
      region has been developed for the direct typing of enteroviruses in clinical
      samples (Ibrahim et al., 2013). This CODEHOP/VP2 PCR strategy as well as the
      CODEHOP/VP1 technique described by Nix et al. (2006), were tested for the
      detection and typing of enteroviruses in wastewater samples. Virus particles were
      first extracted and concentrated from wastewater samples by using respectively
      beef extract and polyethylene glycol 6000, and the presence of enteroviruses was
      screened by a RT-PCR method using primers from the 5'-end non-coding region
      (5'NCR). Fifty-two of 172 samples (30.2%) were revealed positive by the 5'NCR
      method. From these 52 samples, only 19 samples (36.5%) were found positive by at
      least one of the two CODEHOP techniques, with the following distribution:
      VP1(+)/VP2(+)=4 (7.7%), VP1(-)/VP2(+)=13 (25%) and VP1(+)/VP2(-)=2 (3.8%). These
      results illustrate that the direct typing of enteroviruses in environmental
      samples is insensitive, possibly due to the presence of large amounts of
      amplification inhibitors; however, the VP2 method was found able to allow the
      direct detection and typing of c. one-third of the positive environmental
      samples. 

PMID- 25066281
TI  - Blockade of interleukin 6 signalling ameliorates systemic insulin resistance
      through upregulation of glucose uptake in skeletal muscle and improves hepatic
      steatosis in high-fat diet fed mice.
AB  - BACKGROUND & AIMS: Mice fed high-fat diet (HFD) demonstrate obesity-related
      systemic insulin resistance (IR). Aim of this study is to clarify the role of
      interleukin (IL)-6 in IR in vivo focusing on skeletal muscle, adipose tissue and
      liver. METHODS: Plasma markers of IR and hepatic IL-6 signalling were examined in
      eight-week HFD feeding C57/BL6 mice. Furthermore, IR-related molecules in
      skeletal muscles, adipose tissues and livers were investigated following a single
      injection of anti- IL-6 receptor neutralizing antibody (MR16-1) in two-week HFD
      feeding mice. To investigate the role of IL-6 in hepatic steatosis by prolonged
      HFD, hepatic triglyceride accumulation was assessed in eight-week HFD feeding
      mice with continuous MR16-1 treatment. RESULTS: High-fat diet for both 2 and 8
      weeks elevated plasma IL-6, insulin and leptin, which were decreased by MR16-1
      treatment. A single injection of MR16-1 ameliorated IR as assessed by glucose and
      insulin tolerance test, which may be attributable to upregulation of glucose
      transporter type 4 via phosphorylation of AMP-activated protein kinase as well as
      upregulation of peroxisome proliferator-activated receptor alpha in livers and,
      particularly, in skeletal muscles. MR16-1 also decreased mRNA expression of
      leptin and tumour necrosis factor-alpha and increased that of adiponectin in
      adipose tissue. High-fat diet for 8 weeks, not 2 weeks, induced hepatic steatosis
      and increased hepatic triglyceride content, all of which were ameliorated by MR16
      1 treatment. CONCLUSIONS: Blockade of excessive IL-6 stimulus ameliorated HFD
      induced IR in a skeletal muscle and modulated the production of adipokines from
      an early stage of NAFLD, leading to prevention of liver steatosis for a long
      term.

PMID- 25066282
TI  - 6-Acetonyldihydrochelerythrine Is a Potent Inducer of Apoptosis in HCT116 and
      SW620 Colon Cancer Cells.
AB  - 6-Acetonyldihydrochelerythrine (1), a benzophenanthridine alkaloid, isolated from
      the methanol extract of Zanthoxylum capense, displayed potent cytotoxic activity
      in human HCT116 and SW620 colon carcinoma cells, to a higher extent than 5
      fluorouracil (5-FU), the cornerstone chemotherapeutic agent in colon cancer.
      Cytotoxicity of 1 was evaluated by MTS, lactate dehydrogenase (LDH), and Guava
      ViaCount assays. Interestingly, 1 significantly induced cytotoxicity in both cell
      lines, leading to a significant increase in LDH release, as compared to 5-FU.
      Further, Guava ViaCount flow cytometry assays demonstrated that 1 significantly
      increased cell death, as shown by the presence of a significantly higher
      population of apoptotic cells in both cell lines, as compared to cells exposed to
      5-FU. Furthermore, evaluation of nuclear morphology by Hoechst staining of 1
      treated HCT116 and SW620 cells confirmed flow cytometry results, demonstrating a
      marked induction of apoptotic cell death by 1, again to a further extent than
      that elicited by 5-FU. In addition, immunoblot analysis to ascertain the
      molecular events triggered by 1 exposure was performed. The results show that 1
      exposure reduced the steady-state expression and activation of the pro-survival
      proteins ERK5 and Akt and increased the steady-state expression of p53 in both
      HCT116 and SW620 cells. Changes in ERK5 or Akt activation can be ascertained by
      evaluating the ratio of p-ERK5/ERK5 or p-Akt/Akt. In addition, exposure to 1
      reduced expression of XIAP, Bcl-XL, and Bcl-2, while increasing the cleavage of
      poly(ADP-ribose) polymerase in both cell lines. Collectively, the data indicate
      that 6-acetonyldihydrochelerythrine (1) is a potent inducer of apoptosis in
      HCT116 and SW620 cell lines, highlighting its potential relevance in colon
      cancer. 

PMID- 25066283
TI  - Letters to the editor: time for more scholarly debate.

PMID- 25066284
TI  - Psoriasis heritability: 125 years and counting.

PMID- 25066285
TI  - Methotrexate use and liver disease--a causal relationship?

PMID- 25066286
TI  - Inflammatory skin diseases and 'danger' signalling: time to take centre stage?

PMID- 25066287
TI  - Night-time sedating H1 antihistamine increases daytime somnolence but not
      treatment efficacy in chronic spontaneous urticaria: a randomized controlled
      study.

PMID- 25066288
TI  - Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria: a
      critical appraisal.

PMID- 25066289
TI  - Commentary: Omalizumab for the treatment of chronic idiopathic or spontaneous
      urticaria.

PMID- 25066290
TI  - Response to: 'Omalizumab for the treatment of chronic idiopathic or spontaneous
      urticaria: a critical appraisal'.

PMID- 25066294
TI  - Simulated distal interphalangeal joint fusion of the index and middle fingers in
      0 degrees  and 20 degrees  of flexion: a comparison of grip strength and
      dexterity.
AB  - PURPOSE: To evaluate dexterity and grip strength after simulated distal
      interphalangeal (DIP) joint fusion of the index and middle fingers in varying
      degrees of flexion. METHODS: Forty-six right-handed subjects performed grip and
      dexterity testing using the Grooved Pegboard Test in positions of index finger 20
      degrees  flexion or full extension, middle finger 20 degrees  flexion or full
      extension, and unrestricted index and middle finger DIP joint motion (control).
      Simulated fusion was performed with the use of custom-molded thermoplastic
      orthoses. RESULTS: Index finger dexterity scores were improved when the DIP joint
      was splinted in 20 degrees  compared with full extension. There was no
      significant difference in the middle finger dexterity when comparing 20 degrees 
      flexion with full extension. In either position, dexterity scores were higher
      (lower performance) for the index finger than for the middle finger, showing a
      greater interference to dexterity with splinting the index finger DIP joint. Mean
      grip strength was unaffected by middle finger DIP joint position, whereas
      splinting of the index finger in full extension resulted in reduced grip
      strength. CONCLUSIONS: Because positioning the middle finger DIP joint in either
      extension or 20 degrees  of flexion did not significantly affect grip strength or
      dexterity, other considerations such as appearance can be given priority. For the
      index finger, however, positioning the DIP joint in 20 degrees  of flexion may
      improve grip strength and dexterity over positioning it in neutral. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Prognostic I.

PMID- 25066295
TI  - Level of health extension service utilization and associated factors among
      community in Abuna Gindeberet District, West Shoa Zone, Oromia Regional State,
      Ethiopia.
AB  - BACKGROUND: In Ethiopia, children and mothers have been facing several health
      problems due to poor access to modern health care facilities and lack of
      effective demand to utilize the available ones. In response to this, the
      Ethiopian government initiated the health extension program in 2003 to improve
      equity in access to preventive, promotive and selected curative health
      interventions through health extension program. However, the level of health
      extension service utilization is not known. Therefore, this study presents the
      level of health extension service utilization and associated factors. METHODS: A
      community based cross sectional study was carried out from February to March
      2012. Data was collected through face-to-face interview by using pretested
      structured questionnaires adopted from review of different related literatures
      and entered in to EPI Info version 3.5.1. Bivariate analysis between dependent
      and independent variables was performed. Multivariate analysis was also done to
      control for possible confounding variable by selecting variable which show
      statistically significant association (P < 0.2) in bivariate analyses to identify
      independent predictor factors. RESULTS: The proportion of community utilization
      of health extension service was 39%. Age (AOR = 2.52; 95% CI = 1.53-4.15),
      occupation (AOR = 3.79; 95% CI = 1.64-12.5), knowledge of community on health
      extension service (AOR = 0.25; 95% CI = 0.18-0.36), community participation in
      planning of health extension activities (AOR = 0.22; 95% CI = 0.15-0.33) and
      graduation of model family (AOR = 0.74; 95% CI = 0.47-0.76) have statistically
      significant association with community health extension services utilization.
      CONCLUSIONS: The proportion of community utilization of health extension service
      was low. Age, occupation, knowledge of community on health extension service,
      community participation in planning of health extension activities and graduation
      of model family were identified as the independent factors affecting the
      community's utilization of health extension services.

PMID- 25066297
TI  - Phosphorylation of myofibrillogenesis regulator-1 activates the MAPK signaling
      pathway and induces proliferation and migration in human breast cancer MCF7
      cells.
AB  - Myofibrillogenesis regulator-1 (MR-1) has been characterized as a tumor promoter
      in many cancers. However, its mechanism of action has not been fully elucidated.
      Here, we report that MR-1 is overexpressed in human breast cancer cells and
      participates in tumor promotion in human breast cancer MCF7 cells by activating
      the ERK1/2 signaling pathway. MR-1 interacts with MEK1/2 and ERK1, and its N
      terminal sequence plays a major role in promoting the MEK/ERK cascade.
      Furthermore, six phosphorylation sites of MR-1 were identified, and
      phosphorylation at S46 was shown to be critical for the activation of MEK/ERK.
      Therefore, our findings suggest that MR-1 functions as a tumor promoter in MCF7
      cells by activating the MEK/ERK signaling. 

PMID- 25066298
TI  - miR-342-3p suppresses proliferation, migration and invasion by targeting FOXM1 in
      human cervical cancer.
AB  - FOXM1 is a well-established oncogenic factor that has been reported to be
      involved in multiple biological processes including cell proliferation, growth,
      angiogenesis, migration and invasion. It can also be regulated by miRNAs. In this
      study, we reported that FOXM1 is directly targeted by miR-342-3p, which is down
      regulated along with its host gene, EVL, in human cervical cancer tissues
      compared to the adjacent normal tissues. Functional studies suggested that the
      overexpression of miR-342-3p inhibits cell proliferation, migration and invasion
      in cervical cell lines. FOXM1 is upregulated and negatively correlates with miR
      342-3p in cervical cancer tissues, and the overexpression of FOXM1 rescues the
      phenotype changes induced by the overexpression of miR-342-3p. 

PMID- 25066296
TI  - smFRET studies of the 'encounter' complexes and subsequent intermediate states
      that regulate the selectivity of ligand binding.
AB  - The selectivity with which a biomolecule can bind its cognate ligand when
      confronted by the vast array of structurally similar, competing ligands that are
      present in the cell underlies the fidelity of some of the most fundamental
      processes in biology. Because they collectively comprise one of only a few
      methods that can sensitively detect the 'encounter' complexes and subsequent
      intermediate states that regulate the selectivity of ligand binding, single
      molecule fluorescence, and particularly single-molecule fluorescence resonance
      energy transfer (smFRET), approaches have revolutionized studies of ligand
      binding reactions. Here, we describe a widely used smFRET strategy that enables
      investigations of a large variety of ligand-binding reactions, and discuss two
      such reactions, aminoacyl-tRNA selection during translation elongation and splice
      site selection during spliceosome assembly, that highlight both the successes and
      challenges of smFRET studies of ligand-binding reactions. We conclude by
      reviewing a number of emerging experimental and computational approaches that are
      expanding the capabilities of smFRET approaches for studies of ligand-binding
      reactions and that promise to reveal the mechanisms that control the selectivity
      of ligand binding with unprecedented resolution. 

PMID- 25066300
TI  - Word meanings evolve to selectively preserve distinctions on salient dimensions.
AB  - Words refer to objects in the world, but this correspondence is not one-to-one:
      Each word has a range of referents that share features on some dimensions but
      differ on others. This property of language is called underspecification. Parts
      of the lexicon have characteristic patterns of underspecification; for example,
      artifact nouns tend to specify shape, but not color, whereas substance nouns
      specify material but not shape. These regularities in the lexicon enable learners
      to generalize new words appropriately. How does the lexicon come to have these
      helpful regularities? We test the hypothesis that systematic backgrounding of
      some dimensions during learning and use causes language to gradually change, over
      repeated episodes of transmission, to produce a lexicon with strong patterns of
      underspecification across these less salient dimensions. This offers a cultural
      evolutionary mechanism linking individual word learning and generalization to the
      origin of regularities in the lexicon that help learners generalize words
      appropriately. 

PMID- 25066299
TI  - Systematic comparison of bacterial feeding strains for increased yield of
      Caenorhabditis elegans males by RNA interference-induced non-disjunction.
AB  - Rare Caenorhabditis elegans males arise when sex chromosome non-disjunction
      occurs during meiosis in self-fertilizing hermaphrodites. Non-disjunction is a
      relatively rare event, and males are typically observed at a frequency of less
      than one in five hundred wild-type animals. Males are required for genetic
      crosses and phenotypic analysis, yet current methods to generate large numbers of
      males can be cumbersome. Here, we identify RNAi reagents (dsRNA-expressing
      bacteria) with improved effectiveness for eliciting males. Specifically, we used
      RNAi to systematically reduce the expression of over two hundred genes with
      meiotic chromosome segregation functions, and we identified a set of RNAi
      reagents that robustly and reproducibly elicited male progeny. 

PMID- 25066301
TI  - Amyloid-beta (Abeta1-42)-induced paralysis in Caenorhabditis elegans is inhibited
      by the polyphenol quercetin through activation of protein degradation pathways.
AB  - SCOPE: Dietary polyphenols are suggested to play a role in the prevention of
      Alzheimer's disease, of which accumulation of aggregated beta amyloid (Abeta) is
      a key histopathological hallmark. We used the transgenic Caenorhabditis elegans
      strain CL2006, which expresses human Abeta1-42 under control of a muscle-specific
      promoter and responds to Abeta1-42 aggregation with paralysis, to test effects of
      the polyphenol quercetin on the phenotype. METHODS AND RESULTS: Quercetin dose
      dependently decreased the amount of aggregated proteins in solution and also
      paralysis in CL2006. The knockdown of key components of unfolded protein response
      in mitochondria or the endoplasmic reticulum by RNA-interference (RNAi) enhanced
      paralysis in CL2006 but did not prevent the paralysis reducing activities of
      quercetin. RNAi for essential members of proteasomal protein degradation or
      macroautophagy also significantly increased paralysis but prevented quercetin
      from being effective. Quercetin increased proteasomal activity and, moreover,
      enhanced the flow of proteins through the macroautophagy pathway as reflected by
      reduced lysosome staining. CONCLUSION: The proteostasis network, including
      unfolded protein response, defines the aggregation of Abeta1-42 and the
      associated paralysis phenotype in a nematode model for Alzheimer's disease. The
      polyphenol quercetin, by specifically activating macroautophagy and proteasomal
      degradation pathways, proved able to prevent Abeta1-42 agregation and paralysis.

PMID- 25066303
TI  - An Innovative and Simple Approach to Functional Salivary Reservoir Fabrication.
AB  - Saliva is a valuable oral fluid that is often taken for granted. Impaired
      salivary function is a major and a debilitating sequela of radiation treatment
      for patients with head and neck cancer. It can persist for years and thereby
      increases the risk of oral infection significantly. Moreover, it has a notably
      negative impact on the quality of life of such patients. To help overcome this
      problem, a number of techniques have been proposed for incorporating a reservoir
      containing salivary substitute into a removable prosthesis. A new design for a
      functional salivary reservoir is presented here. This design is simple to
      construct and easily maintained by the wearer. Details of its design,
      construction, and other potential advantages are presented. 

PMID- 25066304
TI  - Photocatalytic water oxidation by a mixed-valent Mn(III)3Mn(IV)O3 manganese oxo
      core that mimics the natural oxygen-evolving center.
AB  - The functional core of oxygenic photosynthesis is in charge of catalytic water
      oxidation by a multi-redox Mn(III)/Mn(IV) manifold that evolves through five
      electronic states (S(i), where i=0-4). The synthetic model system of this
      catalytic cycle and of its S0->S4 intermediates is the expected turning point for
      artificial photosynthesis. The tetramanganese-substituted tungstosilicate
      [Mn(III)3Mn(IV)O3(CH3COO)3(A-alpha-SiW9O34)](6-)(Mn4POM) offers an unprecedented
      mimicry of the natural system in its reduced S0 state; it features a hybrid
      organic-inorganic coordination sphere and is anchored on a polyoxotungstate.
      Evidence for its photosynthetic properties when combined with [Ru(bpy)3](2+) and
      S2O8(2-) is obtained by nanosecond laser flash photolysis; its S0->S1 transition
      within milliseconds and multiple-hole-accumulating properties were studied.
      Photocatalytic oxygen evolution is achieved in a buffered medium (pH 5) with a
      quantum efficiency of 1.7%.

PMID- 25066302
TI  - Enhanced brain distribution of modified aspartoacylase.
AB  - Canavan disease is a fatal neurological disorder caused by defects in the gene
      that produces the enzyme aspartoacylase. Enzyme replacement therapy can
      potentially be used to overcome these defects if a stable enzyme form that can
      gain access to the appropriate neural cells can be produced. Achieving the proper
      cellular targeting requires a modified form of aspartoacylase that can traverse
      the blood-brain barrier. A PEGylated form of aspartoacylase that shows dramatic
      enhancement in brain tissue access and distribution has been produced. While the
      mechanism of transport has not yet been established, this modified enzyme is
      significantly less immunogenic than unmodified aspartoacylase. These improved
      properties set the stage for more extensive enzyme replacement trials as a
      possible treatment strategy. 

PMID- 25066305
TI  - Potential for nosocomial transmission of Enterococcus faecalis from surfaces in
      dental operatories.
AB  - AIM: To assess the potential for nosocomial transmission of Enterococcus faecalis
      during root canal treatment by measuring its occurrence on surfaces in dental
      operatories in relation to the efficacy of disinfection routines. METHODOLOGY:
      Eight dental clinics (two endodontic specialist clinics and six general dentistry
      clinics) were included. Bacterial sampling was conducted in duplicate after root
      canal treatment and collected before and after disinfection from four surfaces
      expected to be frequently disinfected and six surfaces expected to be
      occasionally disinfected. RESULTS: A total of 320 samples were collected.
      Overall, 40.6% (n = 130) exhibited bacterial growth, mostly consisting of
      environmental bacteria (36.3%) and to a lesser extent of bacteria from salivary
      contamination (3.4%). Only three surfaces, all of which were probably seldomly
      disinfected, were positive for E. faecalis (0.9%). Disinfection routines resulted
      in an increased contamination in the majority of general dentistry clinics: 64%
      (32/50) of the surfaces were contaminated prior to and 70% (35/50) after
      disinfection. Conversely, disinfection of surfaces in the specialist clinics
      reduced contamination levels by 10%. CONCLUSIONS: The origin of E. faecalis in
      secondary root canal infections remains unclear, as the potential for nosocomial
      transmission of enterococci from environmental surfaces in dental surgeries
      appears to be very small. The incorrect or ineffective disinfection procedures in
      general dentistry clinics needs to be addressed to counteract the risk for
      bacterial transmission in dental operatories.

PMID- 25066306
TI  - Diabetes mellitus is associated with elevated risk of mortality amongst patients
      with prostate cancer: a meta-analysis of 11 cohort studies.
AB  - PURPOSE: Diabetes mellitus is associated with a decreased risk of prostate
      cancer. However, previous studies examining the associations between diabetes
      mellitus and prostate cancer prognosis have produced mixed results. Here, we aim
      to summarize the effect of diabetes mellitus on prostate cancer prognosis.
      METHODS: We searched the database of PubMed from inception through 31 March 2014
      for articles evaluating the effect of diabetes on outcome in prostate cancer
      patients, and a meta-analysis was conducted. RESULTS: A total of 11 cohort
      studies were included in this meta-analysis, of which seven studies were carried
      out to investigate whether diabetes mellitus is associated with all-cause
      mortality amongst those with prostate cancer, seven studies to investigate
      whether diabetes mellitus is associated with prostate cancer-specific mortality
      and two studies to investigate the relationship of diabetes mellitus and
      nonprostate cancer mortality. The meta-analysis results suggested that diabetes
      mellitus could significantly affect the incidence of all-cause mortality amongst
      those with prostate cancer (hazard ratio = 1.50, 95% confidence interval = 1.25
      1.79). Besides, diabetes mellitus was also associated with prostate cancer
      specific mortality (hazard ratio = 1.26, 95% confidence interval = 1.20-1.33) and
      nonprostate cancer mortality (hazard ratio = 1.83, 95% confidence interval = 1.33
      2.52) separately. There was no obvious publication bias amongst the studies
      included. CONCLUSION: The results of this meta-analysis reveal an association of
      diabetes mellitus with adverse prognosis amongst those with prostate cancer. The
      biological basis of the association of diabetes mellitus with prostate cancer
      incidence and prognosis remains unclear. Doctors could pay more attention to
      prostate patients with pre-existing diabetes mellitus, and more aggressive
      treatment regimens should be considered.

PMID- 25066307
TI  - Brief report novel mechanism for valproate-induced teratogenicity.
AB  - BACKGROUND: Valproic acid (VPA) is a commonly prescribed drug for those affected
      by epilepsy and bipolar disorders. VPA has a well known teratogenic potential,
      causing a variety of birth defects including neural tube defects (NTDs) and other
      congenital malformations, when women are treated with this medication during
      pregnancy. Unfortunately, the mechanism by which VPA is teratogenic remains
      unknown, although a range of potential mechanisms including histone deacetylase
      inhibition and folate antagonism have been proposed. The latter is of
      considerable importance, as clinicians need to know if additional folate
      supplements can prevent VPA-induced defects. METHODS: We herein approach this
      question experimentally, using enzyme-linked immunosorbent assay assays and cell
      culture modeling, to demonstrate that VPA serves as a noncompetitive inhibitor of
      the high affinity folate receptors. RESULTS: Binding affinities experimentally
      determined through enzyme-linked immunosorbent assay assays indicate that VPA
      serves as a noncompetitive substrate that can lessen the ability of the three
      primary folate forms to bind to the high affinity folate receptors. Tests in
      HEK293T cells indicate that the membrane-bound folate receptors of VPA treated
      cells bind significantly lower amounts of folic acid than do untreated cells.
      CONCLUSION: If these data translate to the overall transport and subsequent
      bioavailability of folates, noncompetitive inhibition of the folate receptors by
      VPA may serve to lower the bioavailable folates in VPA treated mothers. This
      represents a novel mechanism by which in utero VPA exposure could be disrupting
      developmental processes by noncompetitively binding to the folate receptors
      during embryogenesis, thus inducing the wide range of defects seen in babies born
      to VPA treated mothers.

PMID- 25066309
TI  - The forest and the trees: relational and specific factors in addiction treatment.
AB  - AIMS: Increased expectations for the use of evidence-based methods in addiction
      treatment have fueled a debate regarding the relative importance of 'specific'
      versus 'common' factors in treatment outcome. This review explores the influence
      of these factors on addiction treatment outcome. METHODS: The authors review and
      link findings from four decades of research on specific and general factors in
      addiction treatment outcome research. FINDINGS: Although few would argue that
      what one does in addiction treatment is immaterial, outcome studies tend to find
      small to no difference when specific treatment methods are compared with each
      other or with treatment as usual. In contrast, there are usually substantial
      differences among therapists in client outcomes, and relational factors such as
      therapist empathy and therapeutic alliance can be significant determinants of
      addiction treatment outcome. CONCLUSIONS: In addiction treatment, relational
      factors such as empathy, which are often described as common, non-specific
      factors, should not be dismissed as 'common' because they vary substantially
      across providers and it is unclear how common they actually are. Similarly they
      should not be relegated to 'non-specific' status, because such important
      relational influences can be specified and incorporated into clinical research
      and training.

PMID- 25066308
TI  - Neural response during attentional control and emotion processing predicts
      improvement after cognitive behavioral therapy in generalized social anxiety
      disorder.
AB  - BACKGROUND: Individuals with generalized social anxiety disorder (gSAD) exhibit
      attentional bias to salient stimuli, which is reduced in patients whose symptoms
      improve after treatment, indicating that mechanisms of bias mediate treatment
      success. Therefore, pre-treatment activity in regions implicated in attentional
      control over socio-emotional signals (e.g. anterior cingulate cortex,
      dorsolateral prefrontal cortex) may predict response to cognitive behavioral
      therapy (CBT), evidence-based psychotherapy for gSAD. METHOD: During functional
      magnetic resonance imaging, 21 participants with gSAD viewed images comprising a
      trio of geometric shapes (circles, rectangles or triangles) alongside a trio of
      faces (angry, fearful or happy) within the same field of view. Attentional
      control was evaluated with the instruction to 'match shapes', directing attention
      away from faces, which was contrasted with 'match faces', whereby attention was
      directed to emotional faces. RESULTS: Whole-brain voxel-wise analyses showed that
      symptom improvement was predicted by enhanced pre-treatment activity in the
      presence of emotional face distractors in the dorsal anterior cingulate cortex
      and dorsal medial prefrontal cortex. Additionally, CBT success was foretold by
      less activity in the amygdala and/or increased activity in the medial
      orbitofrontal gyrus during emotion processing. CONCLUSIONS: CBT response was
      predicted by pre-treatment activity in prefrontal regions and the amygdala. The
      direction of activity suggests that individuals with intact attentional control
      in the presence of emotional distractors, regulatory capacity over emotional
      faces and/or less reactivity to such faces are more likely to benefit from CBT.
      Findings indicate that baseline neural activity in the context of attentional
      control and emotion processing may serve as a step towards delineating mechanisms
      by which CBT exerts its effects.

PMID- 25066310
TI  - MMP13 can be a useful differentiating marker between squamous cell carcinoma and
      benign hyperkeratotic lesions in recessive dystrophic epidermolysis bullosa.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is a severe hereditary
      mechanobullous disease resulting from mutations in the COL7A1 gene, coding for
      type VII collagen. Patients with RDEB tend to develop squamous cell carcinomas
      (SCCs) at sites of chronic ulceration or scarring on the whole body.
      Distinguishing SCC from benign hyperkeratotic lesions is often difficult, not
      only clinically but also histologically in patients with RDEB. We investigated
      several matrix metallopeptidase (MMP) subtypes by comparing the DNA amplification
      microarray findings between evident SCCs and benign hyperkeratotic lesions in the
      same patient with RDEB. We report that MMP13 was found to be strongly positive in
      SCCs but negative in benign hyperkeratotic lesions. We found that there is an
      evident difference in the transitional area between SCCs and benign
      hyperkeratotic lesions. We propose that MMP13 may be a useful differentiating
      marker between SCC and benign hyperkeratotic lesions in RDEB. 

PMID- 25066311
TI  - An efficient DNA-fueled molecular machine for the discrimination of single-base
      changes.
AB  - A new strategy for single-base polymorphism (SNP) detection based on the assembly
      of DNA-AuNPs (gold nanoparticles) driven by a DNA-fueled molecular machine, is
      established and optimized. It is highly efficient, works at room temperature, and
      is easy to handle. A single-base change on an oligonucleotide strand is
      unambiguously discriminated for either SNPs or insertions and deletions (indels).
      The strategy is demonstrated to detect a mutation in the breast cancer gene BRCA1
      in homogeneous solution at room temperature. 

PMID- 25066312
TI  - [Author's response to article "Excessive fusion in cervical post-facetectomy
      arthrodesis" by J.M. Gonzalez-Darder].

PMID- 25066313
TI  - Empowering parents for evidence-based fever management: An integrative review.
AB  - PURPOSE: Many parents of young, febrile children lack evidence-based tools to
      manage fever (knowledge, skills, confidence, support), fear negative outcomes,
      and prioritize the reduction of fever over management of its source. This review
      examines the literature for evidence of factors that must be considered when
      designing effective fever management educational interventions for parents,
      especially those whose health literacy is low. DATA SOURCES: A systematic search
      identified studies from 1980 to 2011 using the databases PubMed, CINAHL, Embase,
      Cochrane Review, Web of Science, PsychInfo, Medline Plus, Joanna Briggs
      Institute, and Google Scholar. CONCLUSIONS: The most effective educational
      interventions are 1:1, multidimensional, structured, relevant, and reinforced
      over time. Parental culture, health literacy, knowledge deficits, and beliefs
      must be addressed by nurse practitioners (NPs) to maximize evidence-based
      behaviors. IMPLICATIONS FOR PRACTICE: Parents often strive to do what is best for
      their child but may become overly protective and anxious when managing their
      child's fever. NPs have a prime opportunity to improve parents' fever management
      practices. An evidence-based toolkit, created with respect for those who may have
      low health literacy, will give parents tangible tools to help them provide safer
      and less costly care for their febrile child.

PMID- 25066314
TI  - Unipolar peak-negative voltage as an endocardial electrographic characteristic to
      predict overlying abnormal epicardial substrates in patients with right
      epicardial ventricular tachycardia.
AB  - INTRODUCTION: The characteristics of endocardial electrograms needed to detect
      the overlying abnormal epicardial substrates in arrhythmogenic right ventricular
      cardiomyopathy with epicardial ventricular tachycardia (VT) remain unclear. This
      study investigated which of the endocardial electrogram characteristics could
      predict the overlying abnormal epicardial substrates. METHODS AND RESULTS: In 20
      consecutive patients (median age: 46 years, 11 men) undergoing epicardial VT
      ablation, detailed endocardial and epicardial mappings were obtained by using the
      CARTO 3 system. The endocardial electrographic characteristics (unipolar peak-to
      peak voltage, unipolar peak-negative-voltage, bipolar voltage, and bipolar
      electrogram duration) of the opposite endocardium and epicardium in RV were
      retrospectively investigated (N = 1,697 paired points, 84 +/- 60 pairs/patient).
      Endocardial predictors of the presence of epicardial dense scar (<0.5 mV), low
      voltage zones (LVZ; <=1.5 mV), and ablation targets (by using activation mapping,
      entrainment mapping, and pace mapping) were analyzed. RESULTS: In the
      multivariable analysis, (1) unipolar peak-negative voltage independently
      predicted the presence of epicardial LVZ, epicardial dense scar, and ablation
      targets; (2) bipolar voltage could not predict epicardial lesions; and (3)
      bipolar electrogram duration predicted epicardial LVZ, but not dense scar or
      ablation targets. The endocardial unipolar peak-negative voltage of <1.66 mV (89%
      sensitivity and 53% specificity) was the optimal cutoff point for predicting
      epicardial dense scar. CONCLUSIONS: In patients with RV epicardial VT, the
      presence of unipolar peak-negative voltage of <1.66 mV in the endocardium
      predicted the presence of epicardial dense scar (<0.5 mV) and potential ablation
      targets in the overlying epicardium.

PMID- 25066315
TI  - Long-term tumor necrosis factor treatment induces NFkappaB activation and
      proliferation, but not osteoblastic differentiation of adipose tissue-derived
      mesenchymal stem cells in vitro.
AB  - The pro-inflammatory cytokine tumor necrosis factor (TNF) is well known to induce
      differentiation of bone matrix-resorbing osteoclasts from hematopoietic stem
      cells. However, the impact of TNF on differentiation of bone matrix-forming
      osteoblasts from mesenchymal stem cells (MSC) was only fragmentarily studied so
      far. Therefore, we investigated what impact long-term TNF treatment has on
      osteoblastic differentiation of MSC isolated from the adipose tissue (ASC) in
      vitro. In summary, we found continuous TNF exposure to induce the nuclear factor
      of kappa B pathway in ASC as well as secretion of the pro-inflammatory chemokine
      interleukin 8, but not the mitogen-activated protein kinase and the apoptosis
      pathway in ASC. Moreover, TNF neither induced nor inhibited osteoblastic
      differentiation of ASC, but strongly increased their proliferation rate. In that
      manner, pro-inflammatory conditions in vivo may generate significantly increased
      numbers of progenitor cells, and ASC especially, in conjunction with external
      stimuli, may contribute to the events of ectopic ossification observed in chronic
      inflammatory diseases. The substantiation of the translation of our in vitro
      findings to the disease context encourages further in vivo studies. 

PMID- 25066316
TI  - New inhibitors of the Kvbeta2 subunit from mammalian Kv1 potassium channels.
AB  - The role of the redox state of Kvbeta subunits in the modulation of Kv1 potassium
      channels has been well documented over the past few years. It has been suggested
      that a molecule that binds to or inhibits the aldo-keto reductase activity of
      Kvbeta might affect the modulation of channel properties. Previous studies of
      possible modulators of channel activity have shown that cortisone and some
      related compounds are able to physically dissociate the channel components by
      binding to a site at the interface between alpha and beta subunits. Herein, we
      describe some new inhibitors of rat brain Kvbeta2, identified using an assay
      based on multiple substrate turnover. This approach allows one to focus on
      molecules that specifically block NADPH oxidation. These studies showed that, at
      0.5mM, 3,4-dihydroxphenylacetic acid (DOPAC) was an inhibitor of Kvbeta2 turnover
      yielding a ~ 40-50% reduction in the aldehyde reductase activity of this subunit.
      Other significant inhibitors include the bioflavinoid, rutin and the polyphenol
      resveratrol; some of the known cardioprotective effects of these molecules may be
      attributable to Kv1 channel modulation. Cortisone or catechol caused moderate
      inhibition of Kvbeta2 turnover, and the aldo-keto reductases inhibitor valproate
      had an even smaller effect. Despite the importance of the Kv1 channels in a
      number of disease states, there have been few Kvbeta2 inhibitors reported. While
      the ones identified in this study are only effective at high concentrations, they
      could serve as tools to decipher the role of Kvbeta2 in vivo and, eventually,
      inform the development of novel therapeutics.

PMID- 25066317
TI  - V600E BRAF mutation in pilocytic astrocytoma is associated with a more diffuse
      growth pattern but does not confer a more aggressive clinical behavior.
AB  - Activation in mitogen activated protein kinase signaling pathway has recently
      been described as a predominant event in pilocytic astrocytoma (PA) and is
      commonly caused by constitutively active mutation in BRAF protein. Whereas PA of
      posterior fossa in children have a high prevalence of BRAF duplication and
      fusion, primary molecularm abnormalities in supratentorial tumors of adults are
      more diverse and also include BRAF V600E point mutation. In our study we
      evaluated 51 PAs for BRAF duplication and BRAF V600E point mutation. We found a
      relatively high frequency of V600E mutation in our cohort. Histologically, V600E
      carrying PA appeared more infiltrative, yet our limited clinical follow-up failed
      to detect a deleterious prognostic significance. 

PMID- 25066318
TI  - [Impact of antiviral therapy on the natural history of hepatitis C virus].
AB  - Chronic hepatitis C virus infection affects around 150 million persons, and
      350,000 persons worldwide die of this disease each year. Although the data on its
      natural history are incomplete, after the acute infection, most patients develop
      chronic forms of hepatitis C with variable stages of fibrosis. In these patients,
      continual inflammatory activity can cause significant fibrosis, cirrhosis,
      decompensation of the liver disease, or hepatocarcinoma. In the next few years,
      it is expected that hepatitis C virus infection and its complications will
      significantly increase, as will the incidence of hepatocarcinoma in Spain. This
      review presents the data on the natural history of hepatitis C virus infection
      and discusses the potential impact of antiviral therapy on the distinct stages of
      the disease.

PMID- 25066319
TI  - [Laparoscopic right hemicolectomy due to schwannoma of the colon].

PMID- 25066320
TI  - [Hepatitis B virus infection in pregnancy and the immunosuppressed patient].
AB  - Hepatitis B virus (HBV) infection continues to be a major public health problem
      worldwide. Although treatment indications are well established in clinical
      practice guidelines, there are some risk groups, such as pregnant women and
      immunosuppressed patients, who require different and specific management of HBV
      infection. In pregnant women, treatment indication should be individualized and
      the risk of HBV transmission to the newborn evaluated because cases of vertical
      transmission continue to be reported, despite active and passive
      immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV
      reactivation is associated with high morbidity and mortality, even in patients
      with past HBV infection, highlighting the importance of screening and the need to
      evaluate prophylactic therapy in some cases. 

PMID- 25066322
TI  - G226, a novel epipolythiodioxopiperazine derivative, induces autophagy and
      caspase-dependent apoptosis in human breast cancer cells in vitro.
AB  - AIM: To investigate the effects of G226, a novel epipolythiodioxopiperazine
      derivative, on human breast cancer cells in vitro, and to explore its anticancer
      mechanisms. METHODS: A panel of human breast cancer cell lines (MDA-MB-231, MDA
      MB-468, MCF-7, ZR-75-30, BT474, BT549, SK-BR-3, T47D and HBL100) was examined.
      Cell proliferation was measured using sulforhodamine B assay, and cell apoptosis
      was detected with flow cytometry and caspase activity assay. Western blotting,
      immunofluorescence and targeted gene knockdowns were used to study autophagy in
      the cells. RESULTS: G226 suppressed proliferation of the 9 breast cancer cell
      lines with a mean IC50 value of 48.5 nmol/L (the mean IC50 value of adriamycin, a
      reference compound, was 170.6 nmol/L). G226 induced dose-dependent apoptosis of
      MDA-MB-231 and MCF-7 cells, accompanied by markedly increased activities of
      caspase-8 and caspase-3/7, which were abolished by caspase inhibitors zVAD or
      zIETD. G226 also induced mitochondrial outer membrane permeabilization, resulted
      in the caspase-9 activation. Moreover, G226 dose-dependently enhanced the
      autophagy marker LC3-II and autophagy substrate p62 accumulation in the cells,
      which were co-localized with caspase-8. Silencing of p62 or LC3 partially
      diminished caspase-8 and subsequent caspase-3 activation. LC3 silencing partially
      reversed G226-induced apoptosis, but p62 silencing elicited a subtle effect on
      G226-induced apoptosis. CONCLUSION: The novel epipolythiodioxopiperazine
      derivative G226 exerts potent anticancer action against human breast cancer cells
      in vitro, via triggering autophagy and caspase-dependent apoptosis.

PMID- 25066321
TI  - Alcohol use disorders and current pharmacological therapies: the role of GABA(A)
      receptors.
AB  - Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence,
      which create large problems both for society and for the drinkers themselves. To
      date, no therapeutic can effectively solve these problems. Understanding the
      underlying mechanisms leading to AUD is critically important for developing
      effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to
      reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs
      causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA
      approved naltrexone and acamprosate have shown mixed results in clinical trials.
      Naltrexone is effective to treat alcohol dependence (decreased length and
      frequency of drinking bouts), but its severe side effects, including withdrawal
      symptoms, are difficult to overcome. Acamprosate showed efficacy for treating
      alcohol dependence in European trials, but two large US trials have failed to
      confirm the efficacy. Another FDA-approved medication, disulfiram, does not
      diminish craving, and it causes a peripheral neuropathy. Kudzu is the only
      natural medication mentioned by the National Institute on Alcohol Abuse and
      Alcoholism, but its mechanisms of action are not yet established. It has been
      recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has
      unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal
      in alcoholic animal models. In this article, we review the role of GABAA
      receptors in the treatment of AUD and currently available and potentially novel
      pharmacological agents. 

PMID- 25066323
TI  - Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A
      protease.
AB  - AIM: To discover novel hepatitis C virus (HCV) inhibitors and elucidate the
      mechanism of action of the active compounds. METHODS: HCV subgenomic replicon
      based luciferase reporter cell line was used to screen 1200 synthetic compounds
      with novel structures. Huh7.5.1 cell line stably transfected with HCV NS3/4A
      protease reporter was established to investigate the anti-HCV mechanism of the
      active compounds. The active compounds were further examined in an in vitro HCV
      infection assay to confirm their anti-HCV activity. RESULTS: After two-round
      screening in the anti-HCV replicon assay, some 2,4-diaminoquinazoline derivatives
      and carboxamide analogues were found to possess anti-HCV replicon activities (the
      IC50 values were less than 5 MUmol/L). Among them, two representative compounds
      HZ-1157 and LZ-110618-6 inhibited HCV NS3/4A protease with IC50 values of 1.0 and
      0.68 MUmol/L, respectively. Furthermore, HZ-1157 and LZ-110618-6 inhibited HCV
      infection in vitro with IC50 values of 0.82 and 0.11 MUmol/L, respectively.
      CONCLUSION: Some 2,4-diaminoquinazoline derivatives and carboxamide analogues
      have been identified as novel anti-HCV compounds.

PMID- 25066325
TI  - The ethos of science and misconduct in science.

PMID- 25066324
TI  - P selectins and immunological profiles in HCV and Schistosoma mansoni induced
      chronic liver disease.
AB  - BACKGROUND: Hepatitis C virus (HCV) and Schistosoma mansoni are major causes of
      chronic liver disease (CLD) in which immune alteration is common. Recent studies
      suggested that certain platelets and lymphocytes activation markers may have an
      impact on progression of CLD. This study aimed to evaluate the potential of
      platelets and lymphocytes activation molecules expression on the pathogenesis of
      CLD in distinct or concomitant chronic HCV and schistosomiasis mansoni
      infections. METHODS: The study populations were divided into group-I: patients
      with chronic schistosomiasis mansoni, group-II: HCV patients without cirrhosis,
      group-III: patients with combined liver diseases without cirrhosis, group-IV:
      patients with chronic HCV and liver cirrhosis and group-V: Age and sex matched
      healthy individuals as normal controls. All groups were subjected to full
      clinical evaluation, ELISA anti-HCV antibodies screening, parasitological
      examination for diagnosing S. mansoni and flow cytometry for lymphocyte (CD3,
      CD4, CD8, CD19, CD22, & CD56) and platelets activation (CD41, CD42 & CD62P (P-
      selectins)) markers. RESULTS: The platelet count was significantly decreased in
      HCV and/or S. mansoni patients. The total T-lymphocytes and T-helper cells were
      significantly reduced, while T-cytotoxics were increased. The patients possessed
      a significantly higher platelets activation marker; CD62P (P-selectins) and
      higher mean fluorescent intensity (MFI) positivity. There were considerable
      correlations between platelets count and both of CD62P and MFI. CONCLUSION: Our
      Findings suggest an increased expression of certain platelets and lymphocytes
      activation markers in chronic HCV and S. mansoni induced CLD that may have a role
      in disease progression.

PMID- 25066326
TI  - Predictors of valued everyday occupations, empowerment and satisfaction in day
      centres: implications for services for persons with psychiatric disabilities.
AB  - This study addresses predictors of occupational value, empowerment and
      satisfaction with the rehabilitation received in day centres for people with
      psychiatric disabilities. These outcomes represent varying aspects of relevance
      for the day centre context and together create a manifold outcome picture. This
      was a longitudinal study with approval from the regional research vetting board.
      Self-report instruments were used, and the investigated predictors motivation for
      going to the day centre, occupational engagement, socio-demographic factors and
      self-reported diagnosis. Attendees (N = 108) at 8 day centres participated and
      filled in self-report questionnaires regarding the predictor and outcome
      variables. A baseline measurement and a 14-month follow-up composed the data.
      Occupational engagement at baseline could predict all three outcomes at the
      follow-up. Motivation for the day centre activities and not preferring work
      before attending the day centre were positive for satisfaction with the day
      centre. A low participation rate, although comparable with previous studies on
      the target group, was a limitation of this study. To conclude, both occupational
      engagement and motivation are factors that can be stimulated by the staff in day
      centres. Actions for how to accomplish that, and thereby also more positive
      outcomes of the day centre services, are proposed, such as a system of freedom of
      choice among day centres, and between day centres and supported employment.

PMID- 25066327
TI  - The narrative structure as a way to gain insight into peoples' experiences: one
      methodological approach.
AB  - The narrative method is used in healthcare research, mostly in data collection
      but also in the analysis. Narrative approaches draw attention to how people tell
      about and create meaning of experiences. The aim of the article was to examine
      the narrative structure, the elements in the structure and their function and how
      these can be used in research to gain insights into experiences. Examples are
      taken from a material of narratives from a study where next of kin were asked to
      narrate their experiences of sudden and unexpected death from stroke. The
      narratives had a clear beginning, midpoint and ending. In the beginning,
      orientation of the narrated events was given. The narrated events were told to
      have a turning point constituted of complicating actions that lead to a
      resolution that solved the narrated event. The narratives were built up by
      multiple recaps into the narrated events and also consisted of asides - side
      narratives and flashbacks - events back in time. Use of a narrative structure can
      contribute with valuable information that might be missed with other analysis.
      The analysis can be used on its own, as a complement to other narrative analysis
      or even as a complement to other qualitative analysis. 

PMID- 25066328
TI  - The onset and offset of psychosis--and what happens in between--a commentary on
      'Reappraising the long-term course and outcome of psychotic disorders: the AESOP
      10 Study' by Morgan et al. (2014).
AB  - As one would expect for a heterogeneous syndrome like schizophrenia, at the
      individual level the course of symptoms and disability vary widely. Mindful that
      the definition of recovery/remission varies widely between studies, a recent
      systematic review and meta-analysis reported that the proportion of those with
      schizophrenia who recover on both symptom and functional outcome is modest
      (approximately 14%). A 10-year follow-up of the English multicentre AESOP
      incidence study provides more 'fine-grained' insights into the time course of
      symptom fluctuation for schizophrenia and other psychotic disorders. We highlight
      selected findings from the new study and speculate on the role of different
      outcome domains for future study (e.g., symptom, occupational/functional,
      cognition, physical health, patient-nominated outcomes). Because recovery is a
      multifaceted process, we need to develop a panel of practical and
      operationalizable criteria for remission and recovery.

PMID- 25066329
TI  - Non-invasive positive pressure ventilation for the treatment of severe stable
      chronic obstructive pulmonary disease: a prospective, multicentre, randomised,
      controlled clinical trial.
AB  - BACKGROUND: Evidence is weak for the ability of long-term non-invasive positive
      pressure ventilation (NPPV) to improve survival in patients with stable
      hypercapnic chronic obstructive pulmonary disease (COPD). Previous prospective
      studies did not target a reduction in hypercapnia when adjusting ventilator
      settings. This study investigated the effect of long-term NPPV, targeted to
      markedly reduce hypercapnia, on survival in patients with advanced, stable
      hypercapnic COPD. METHODS: This investigator-initiated, prospective, multicentre,
      randomised, controlled clinical trial enrolled patients with stable GOLD stage IV
      COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or
      higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at
      least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients
      were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation
      sequence with a block size of four, to continue optimised standard treatment
      (control group) or to receive additional NPPV for at least 12 months
      (intervention group). The primary outcome was 1-year all-cause mortality.
      Analysis was by intention to treat. The intervention was unblinded, but outcome
      assessment was blinded to treatment assignment. This study is registered with
      ClinicalTrials.gov, number NCT00710541. FINDINGS: Patients were recruited from 36
      respiratory units in Germany and Austria, starting on Oct 29, 2004, and
      terminated with a record of the vital status on July 31, 2011. 195 patients were
      randomly assigned to the NPPV group (n=102) or to the control group (n=93). All
      patients from the control group and the NPPV group were included in the primary
      analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group
      and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11
      0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be
      managed by changing the type of the mask. No other intervention-related adverse
      events were reported. INTERPRETATION: The addition of long-term NPPV to standard
      treatment improves survival of patients with hypercapnic, stable COPD when NPPV
      is targeted to greatly reduce hypercapnia. FUNDING: German Lung Foundation;
      ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.

PMID- 25066330
TI  - Maternal propensity for infections and risk of childhood asthma: a registry-based
      cohort study.
AB  - BACKGROUND: Maternal use of antibiotics during pregnancy has been associated with
      the development of asthmatic disorders in the offspring. The human microbiome has
      been suggested to act as an intermediary in this process. To provide
      clarification on this theory, we studied the temporal relation between maternal
      use of antibiotics and the risk of childhood asthma. METHODS: According to
      national registries, during the observation period (1997-2010), 910,301 children
      were born in Denmark and were included in the analysis. From these registries,
      data for cases of childhood asthma were obtained based on hospital admissions,
      outpatient attendance at a hospital, or use of inhaled corticosteroids. The
      effect of timing of maternal antibiotic use on the risk of asthma in the
      offspring was studied by analysis of maternal antibiotic use in the 80 weeks
      before pregnancy, during pregnancy, and the 80 weeks after pregnancy. Results
      were adjusted for age and calendar year, birthweight, gestational age, sex, mode
      of delivery, parity, multiple births, season of birth, and several maternal
      factors (age, smoking during pregnancy, employment status, and asthma). FINDINGS:
      In this study, we replicated our previous finding that maternal use of
      antibiotics in pregnancy was associated with an increased risk of childhood
      asthma: the adjusted incidence rate ratio (aIRR) was 1.24 (95% CI 1.18-1.30) for
      inpatient admission, 1.22 (1.18-1.26) for outpatient attendance, and 1.18 (1.15
      1.20) for inhaled corticosteroid use. A similar and independent association was
      also recorded for maternal antibiotic use in the 80 weeks before and after the
      pregnancy. A dose-related association occurred between the risk of childhood
      asthma and the number of maternal antibiotic treatments and was recorded
      separately for antibiotic treatment for respiratory tract infections and for
      other types of infections. INTERPRETATION: Maternal use of antibiotics has a dose
      related association with the risk of asthma in the offspring, but this
      association is independent of the temporal relationship with the pregnancy
      period. This finding suggests that maternal antibiotic use is a surrogate marker
      of a mother's general propensity for infections as the underlying link between a
      mother's use of antibiotics and risk of asthma in the offspring. FUNDING: The
      Danish Council for Strategic Research, The Lundbeck Foundation, The Pharmacy
      Foundation of 1991, the Danish Medical Research Council, and National Finance
      Act.

PMID- 25066332
TI  - Domiciliary NIV for COPD: where are we now?

PMID- 25066333
TI  - Maternal antibiotic use and childhood asthma: the missing link?

PMID- 25066331
TI  - Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia
      in patients with severe traumatic brain injury (Corti-TC): a double-blind,
      multicentre phase 3, randomised placebo-controlled trial.
AB  - BACKGROUND: Hospital-acquired pneumonia is common after traumatic brain injury,
      and might be partly a result of traumatic brain injury-induced adrenal
      insufficiency. We tested the efficacy of low-dose hydrocortisone with
      fludrocortisone for the prevention of hospital-acquired pneumonia. METHODS: We
      did this double-blind, phase 3, placebo-controlled trial in 19 intensive care
      units in France. We enrolled patients aged 15-65 years in the first 24 h after
      severe traumatic brain injury (Glasgow coma scale score <=8 and trauma-associated
      lesion on brain CT scan). Patients were randomly assigned (1:1; fixed blocks of
      12, stratified by centre and mechanism, Glasgow coma scale, age, and arterial
      pressure [MGAP] score) to receive either hydrocortisone (200 mg per day tapered)
      and fludrocortisone (50 MUg tablet once per day) or matching placebo for 10 days.
      Before receiving study drug, adrenal function was assessed with a short
      corticotropin test. Treatment was stopped if patients had no adrenal
      insufficiency. The primary outcome was the occurrence of hospital-acquired
      pneumonia within 28 days after randomisation. We did an intention-to-treat
      analysis and a modified intention-to-treat analysis including only patients with
      adrenal insufficiency (adjusted for etomidate use). This study is registered with
      ClinicalTrials.gov, number NCT01093261. FINDINGS: From Sept 1, 2010, to Nov 29,
      2012, we enrolled 336 patients (168 assigned to each group). Eight patients
      withdrew consent. At day 28, 74 of 165 patients (45%) in the steroid group and 87
      of 163 (53%) in the placebo group had developed one or more episodes of hospital
      acquired pneumonia (hazard ratio [HR] 0.75; 95% CI 0.55-1.03, p=0.07). In
      intention-to-treat analysis, we recorded 86 episodes of hospital-acquired
      pneumonia in the steroid group versus 110 in the placebo group (median 0, IQR 0-1
      vs median 1, IQR 0-1 cases per patient, p=0.07). In modified intention-to-treat
      analyses, the HR for hospital-acquired pneumonia with steroids versus placebo was
      0.80 (95% CI 0.56-1.14, p=0.22) in patients with adrenal insufficiency, and, in
      an exploratory preplanned analysis, 0.48 (0.23-1.01; p=0.05) in patients with
      normal adrenal function. We recorded no adverse events related to treatment.
      INTERPRETATION: Low-dose hydrocortisone with fludrocortisone did not improve the
      outcome of patients with traumatic brain injury. However, the study was
      underpowered because the proportion of patients with hospital-acquired pneumonia
      in the placebo group was lower than expected. The results were close to
      statistical significance for efficacy, meaning that further studies are therefore
      needed. FUNDING: Societe Francaise d'Anesthesie Reanimation.

PMID- 25066334
TI  - Prevention of pneumonia after severe traumatic brain injury.

PMID- 25066336
TI  - Refining the latent structure of neuropsychological performance in schizophrenia.
AB  - BACKGROUND: Elucidating the cognitive architecture of schizophrenia promises to
      advance understanding of the clinical and biological substrates of the illness.
      Traditional cross-sectional neuropsychological approaches differentiate impaired
      from normal cognitive abilities but are limited in their ability to determine
      latent substructure. The current study examined the latent architecture of
      abnormal cognition in schizophrenia via a systematic approach. METHOD:
      Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were
      carried out on a large neuropsychological dataset including the Brief Assessment
      of Cognition in Schizophrenia, Continuous Performance Test, Wisconsin Card
      Sorting Test, Benton Judgment of Line Orientation Test, and Wechsler Abbreviated
      Scale of Intelligence matrix reasoning derived from 1012 English-speaking ethnic
      Chinese healthy controls and 707 schizophrenia cases recruited from in- and out
      patient clinics. RESULTS: An initial six-factor model fit cognitive data in
      healthy and schizophrenia subjects. Further modeling, which accounted for
      methodological variance between tests, resulted in a three-factor model of
      executive functioning, vigilance/speed of processing and memory that appeared to
      best discriminate schizophrenia cases from controls. Factor analytic-derived g
      estimands and conventionally calculated g showed similar case-control
      discrimination. However, agreement analysis suggested systematic differences
      between both g indices. CONCLUSIONS: Factor structures derived in the current
      study were broadly similar to those reported previously. However, factor
      structures between schizophrenia subjects and healthy controls were different.
      Roles of factor analytic-derived g estimands and conventional composite score g
      were further discussed. Cognitive structures underlying cognitive deficits in
      schizophrenia may prove useful for interrogating biological substrates and
      enriching effect sizes for subsequent work.

PMID- 25066337
TI  - Relationships between the QTc interval and cardiovascular, stroke, or sudden
      cardiac mortality in the general Japanese population.
AB  - BACKGROUND: We attempted to evaluate whether the relationship between the QTc
      interval and mortality (including sudden cardiac death) is linear or J-shaped in
      the general Japanese population, who tend to be at greater risk of strokes than
      cardiac events. METHODS: We classified 10,804 subjects according to their Bazett
      QTc interval quartiles (determined by electrocardiography) at the baseline and
      followed them up for a mean period of 141.9+/-28.3 months (127,712 person-years).
      RESULTS: In total, 878 subjects died during the study period, including 104 from
      cardiovascular events, 100 from stroke, and 46 from sudden cardiac death. In a
      Cox proportional hazards regression model adjusted for conventional
      cardiovascular risk factors, the risk of cardiovascular mortality increased
      progressively with the QTc interval quartile [Q2, hazard ratio (HR)=0.94 (0.43
      2.03); Q3, HR=1.11 (0.53-2.34); Q4, HR=2.21 (1.12-4.36); HR are vs. Q1]. A
      parallel analysis found that the risk of stroke mortality was marginally
      increased in the highest Bazett QTc interval quartile [HR=1.93 (0.97-3.85)]. On
      the other hand, the risk of sudden cardiac death exhibited a J-shaped
      relationship with the Bazett QTc interval quartile [Q1, HR=8.58 (1.07-69.05); Q3,
      HR=7.17 (0.88-58.73); Q4, HR=13.18 (1.72-101.03); HR are vs. Q2]. CONCLUSION: In
      the general Japanese population, cardiovascular and stroke mortality increase
      progressively with the Bazett QTc interval quartile, while the risk of sudden
      cardiac death exhibits a J-shaped relationship with the latter variable.

PMID- 25066335
TI  - Osteoarthritis joint pain: the cytokine connection.
AB  - Osteoarthritis is a chronic and painful disease of synovial joints. Chondrocytes,
      synovial cells and other cells in the joint can express and respond to cytokines
      and chemokines, and all of these molecules can also be detected in synovial fluid
      of patients with osteoarthritis. The presence of inflammatory cytokines in the
      osteoarthritic joint raises the question whether they may directly participate in
      pain generation by acting on innervating joint nociceptors. Here, we first
      provide a systematic discussion of the known proalgesic effects of cytokines and
      chemokines that have been detected in osteoarthritic joints, including TNF-alpha,
      IL-1, IL-6, IL-15, IL-10, and the chemokines, MCP-1 and fractalkine.
      Subsequently, we discuss what is known about their contribution to joint pain
      based on studies in animal models. Finally, we briefly discuss limited data
      available from clinical studies in human osteoarthritis. 

PMID- 25066338
TI  - Clinical utility of new bleeding criteria: a prospective study of evaluation for
      the Bleeding Academic Research Consortium definition of bleeding in patients
      undergoing percutaneous coronary intervention.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical utility of the new
      bleeding criteria, proposed by the Bleeding Academic Research Consortium (BARC),
      compared with the old criteria for determining the action of physicians in
      contact with bleeding events, after percutaneous coronary intervention (PCI).
      BACKGROUND: The BARC criteria were independently associated with an increased
      risk of 1-year mortality after PCI, and provided a predictive value, in regard to
      1-year mortality. The standardized bleeding definitions will be expected to help
      the physician to correctly analyze the bleeding events, to select an optimal
      treatment, and to objectively compare the results of multiple trials and
      registries. METHODS: All the patients undergoing PCI from June to September 2012
      were prospectively enrolled. Patients who experienced a bleeding event were
      further classified, based on three different bleeding severity criteria: BARC,
      Thrombolysis In Myocardial Infarction (TIMI), and Global Use of Strategies To
      Open coronary arteries (GUSTO). The primary outcome was the occurrence of
      bleeding events requiring interruption of antiplatelet therapy (IAT) by
      physicians. RESULTS: A total of 376 consecutive patients were included in this
      study. Total bleeding events occurred in 46 patients (12.2%). BARC type >=2
      bleeding occurred in 30 patients (8.0%); however, TIMI major or minor bleeding,
      and GUSTO moderate or severe bleeding occurred in 6 (1.6%) and 11 patients
      (2.9%), respectively. Of the 46 patients, 28 (60.9% of patients) required IAT. On
      receiver-operating characteristic curve analysis, bleeding defined BARC type >=2
      effectively predicted IAT, with a sensitivity of 89.3%, and a specificity of
      98.5% (p<0.001), compared with TIMI (sensitivity, 21.4%; specificity, 100%;
      p<0.001), and GUSTO (sensitivity, 39.3%; specificity, 100%; p<0.001).
      CONCLUSIONS: Compared with TIMI and GUSTO, the BARC definition may be a more
      useful tool for the detection of bleeding with clinical relevance, for patients
      undergoing PCI.

PMID- 25066339
TI  - Effects of silver nanoparticles exposure in the mussel Mytilus galloprovincialis.
AB  - Silver nanoparticles (Ag NPs) have emerged as one of the most commonly used NPs
      in a wide range of industrial and commercial applications. This has caused
      increasing concern about their fate in the environment as well as uptake and
      potential toxicity towards aquatic organisms. Accordingly, mussels Mytilus
      galloprovincialis were exposed to 10 MUg L(-1) of Ag NPs and ionic silver (Ag+)
      for 15 days, and biomarkers of oxidative stress and metal accumulation were
      determined. Accumulation results show that both Ag NPs and Ag+ accumulated in
      both gills and digestive glands. Antioxidant enzymes (superoxide dismutase,
      catalase and glutathione peroxidase) were activated by Ag NPs and Ag+, showing
      different antioxidant patterns in both gills and digestive glands. Moreover,
      metallothionein was inducted in gills, directly related to Ag accumulation, while
      in the digestive glands only a small fraction of Ag seems to be associated with
      this protein. Lipid peroxidation was higher in gills exposed to Ag NPs, whereas
      in the digestive glands only Ag+ induced lipid peroxidation. Ag NPs and Ag+ cause
      oxidative stress with distinct modes of action and it's not clear if for Ag NPs
      the observed effects are attributed to free Ag+ ions associated with the
      nanoparticle effect.

PMID- 25066340
TI  - Comparative study of maximum likelihood and spectral angle mapper algorithms used
      for automated detection of melanoma.
AB  - BACKGROUND: Melanoma is a leading fatal illness responsible for 80% of deaths
      from skin cancer. It originates in the pigment-producing melanocytes in the basal
      layer of the epidermis. Melanocytes produce the melanin (the dark pigment), which
      is responsible for the color of skin. As all cancers, melanoma is caused by
      damage to the DNA of the cells, which causes the cell to grow out of control,
      leading to a tumor, which is much more dangerous if it cannot be found or
      detected early. Only biopsy can determine exact malformation diagnosis, although
      it can rise metastasizing. When a melanoma is suspected, the usual standard
      procedure is to perform a biopsy and to subsequently analyze the suspicious
      tissue under the microscope. METHODS: In this paper, we provide a new approach
      using methods known as 'imaging spectroscopy' or 'spectral imaging' for early
      detection of melanoma using two different supervised classifier algorithms,
      maximum likelihood (ML) and spectral angle mapper (SAM). SAM rests on the
      spectral 'angular distances' and the conventional classifier ML rests on the
      spectral distance concept. RESULTS AND CONCLUSIONS: The results show that the ML
      classifier was more efficient for pixel classification than SAM. However, SAM was
      more suitable for object classification.

PMID- 25066341
TI  - [An era ends: expressing thanks to Bernd Rolle].

PMID- 25066342
TI  - [Knowledge transfer and implementation].

PMID- 25066343
TI  - [Hospitalisations for ambulatory care sensitive conditions in Germany].
AB  - BACKGROUND: On the basis of the assumption that a significant proportion of
      hospitalisations for so-called ambulatory care sensitive conditions (ACSCs) are
      potentially avoidable by ambulatory care measures, hospitalisation rates for
      ACSCs are used internationally as population based indicators for access to and
      quality of ambulatory care. The German Council of Health Experts proposes
      hospitalisation rates for diabetes, asthma, hypertension and chronic heart
      failure as ACSC measures in Germany. OBJECTIVES: This article focuses on regional
      differences in ACSC rates, describes the longitudinal development and explores
      potential determinants. MATERIAL AND METHODS: Descriptive statistical analyses as
      well as spatial regression analyses were performed on the basis of Federal
      Statistical Office data. We included data from the hospital and physician
      statistics. Bayesian spatial regression techniques were used. RESULTS: Whereas
      hospitalisation rates for asthma decreased between 2000 and 2010, hospitalisation
      rates for diabetes, hypertension and chronic heart failure increased. Comparing
      age-adjusted ACSC rates across all German federal states, the Eastern states as
      well as Saarland showed significantly higher ACSC rates over time. This
      observation can in part be explained by physician density and the number of
      hospital beds. CONCLUSION: Although not all ACSC hospitalisations can be avoided,
      these results display a potential for optimising care across healthcare sectors
      in Germany.

PMID- 25066344
TI  - [Structured medication management in primary care - a tool to promote medication
      safety].
AB  - Patients with chronic disease usually need to take multiple medications. Drug
      related interactions, adverse events, suboptimal adherence, and self-medication
      are components that can affect medication safety and lead to serious consequences
      for the patient. At present, regular medication reviews to check what medicines
      have been prescribed and what medicines are actually taken by the patient or the
      structured evaluation of drug-related problems rarely take place in Germany. The
      process of "medication reconciliation" or "medication review" as developed in the
      USA and the UK aim at increasing medication safety and therefore represent an
      instrument of quality assurance. Within the HeiCare((r)) project a structured
      medication management was developed for general practice, with medical assistants
      playing a major role in the implementation of the process. Both the structured
      medication management and the tools developed for the medication check and
      medication counselling will be outlined in this article; also, findings on
      feasibility and acceptance in various projects and experiences from a total of
      200 general practices (56 HeiCare((r)), 29 HiCMan,115 PraCMan) will be described.
      The results were obtained from questionnaires and focus group discussions. The
      implementation of a structured medication management intervention into daily
      routine was seen as a challenge. Due to the high relevance of medication
      reconciliation for daily clinical practice, however, the checklists - once
      implemented successfully - have been applied even after the end of the project.
      They have led to the regular review and reconciliation of the physicians'
      documentation of the medicines prescribed (medication chart) with the medicines
      actually taken by the patient. 

PMID- 25066345
TI  - [Developing a tailored intervention: implementing recommendations for
      polypharmacy in multimorbid patients (PomP)].
AB  - INTRODUCTION: Implementation research deals with the question of how to ensure
      that evidence-based knowledge is put into practice. One approach is the
      development of "tailored interventions (TI)". These are designed to address
      previously identified barriers and enablers. A common definition or
      methodological concept for TI has not yet been established. In this paper, a
      concept for TI is introduced. We describe the stepwise development of an
      implementation intervention for GP settings where recommendations based on
      current evidence are provided for the treatment of multimorbid patients receiving
      polypharmacy. Each step will be explained and illustrated by original data.
      METHODS/RESULTS: A stepwise approach was used to develop a TI: problem analysis,
      identification and prioritisation of determinants, identification and
      prioritisation of strategies and the design of a complex intervention and its
      underlying logic model. DISCUSSION: The stepwise exemplary description of this
      tailoring strategy may support other researchers in this field when designing a
      TI.

PMID- 25066346
TI  - [Overcoming language barriers with telephone interpreters: first experiences at a
      German children's hospital].
AB  - Language barriers in the care for patients with limited German language
      proficiency contribute to impaired quality of care, more frequent medical errors
      and decreased patient satisfaction. However, professional interpreters are not
      systematically used in Germany. We conducted a pilot study in a German paediatric
      hospital to explore the demand for an interpreter by conducting a survey among
      parents and to test the use of telephone interpreters. Eight percent of the
      respondents said they were interested in interpreter support. All physicians and
      parents using a telephone interpreter were very satisfied with the quality and
      the organisation of the service. 

PMID- 25066347
TI  - [General practitioner relevant recommendations in German cancer guidelines: a
      systematic review].
AB  - BACKGROUND: As part of the "Cancer Care in the Family Practice" project sponsored
      by the German Cancer Aid association, this overview for the first time assesses
      to what extent general practitioners (GPs) are considered in the formulation of
      German cancer guidelines. METHODS: Guidelines relating to cancer care for adult
      patients were sought in eight national guideline and specialist association
      portals. Identified guidelines were initially examined to discover whether they
      referred to health care programmes, which were specifically developed for general
      practice, whether GPs were involved in their development, and whether GPs were
      regarded, either directly or at least indirectly, as a target group.
      Subsequently, all recommendations that were relevant to GPs were assigned to
      various main categories (communication, treatment measures) as well as
      subcategories and quantitatively assessed. RESULTS: Of a total of 559 hits, 29
      relevant guidelines were identified, of which 21 clearly referred to cancer care
      programmes in general practice. Eight guidelines reported that GPs were involved
      in the development of the guideline, and in four GPs were directly addressed as a
      target group. The majority of relevant recommendations were assigned to the
      category 'communication' but often included recommendations for the
      implementation of measures that were not directly applicable to family doctors
      (such as diagnosis and therapy). Relevant recommendations were found mostly in S3
      guidelines. CONCLUSIONS: Not a single cancer guideline mentioned family practice
      health care programmes, and less than half of them involved family doctors in
      their development process. Most recommendations from cancer guidelines could not
      be directly implemented by GPs. The guideline's development stage and subject
      matter (tumour-specific or across all tumour entities) appeared to influence its
      potential relevance to GPs.

PMID- 25066348
TI  - [Interdisciplinary teamwork in the OR: Identification and measurement of teamwork
      in the operating room].
AB  - Effective teamwork is one of the essentials in conducting successful and safe
      surgical procedures in the operating theatre (OT). The present paper aims to
      provide a selective review of various approaches describing effective
      interdisciplinary teamwork in the OT. Furthermore, it covers observational
      methods to assess OT teamwork with particular focus on Germany. Our definition of
      successful surgical teamwork is based on an already established classification
      system considering five criteria for effective and safe OT teams: coordination,
      communication, cooperation, leadership, and team monitoring. Well-defined and
      reliable measures are necessary to examine the quality of OT teamwork. Those
      methods should entail the special characteristics of the OT team. They should
      include all phases of the surgical procedure and incorporate all the professions
      involved (surgeons, surgical nurses, and anaesthetic staff). We conclude that
      research into methods for the assessment of OTs in Germany needs to be undertaken
      as a prerequisite to investigating the relationship between OT teamwork and its
      effects on patient safety and surgical quality. 

PMID- 25066349
TI  - [Development of a workable mini checklist to assess guideline quality].
AB  - BACKGROUND: Due to lack of time, a detailed appraisal of guideline quality with
      complex assessment instruments such as AGREE and DELBI is not always feasible.
      Therefore, our aim was to develop an assessment tool in the form of a 'mini
      checklist' that would make it possible to quickly gauge guideline quality.
      METHOD: 1. A systematic literature search in MEDLINE, EMBASE and international
      guideline portals for available assessment tools (cut-off value for relevance:
      mentioned in > 50% of cases). 2. Assessment of all identified appraisal criteria
      in an online survey among members of the DELBI 2.0 group of experts (cut-off
      value for relevance: mentioned in > 75% of cases). 3. Internal Delphi technique
      and consensus. RESULTS: 489 requirements for the methodological quality of
      guidelines were extracted from 24 identified assessment instruments. These could
      be merged to create 49 appraisal criteria that were then evaluated by 28 of the
      experts approached (response rate: 43 %). Initially, 8 appraisal criteria reached
      both cut-off values. Seven additional appraisal criteria were adopted by
      consensus. According to the orientation of their content, the 15 appraisal
      criteria were then grouped together to form the 8 appraisal criteria that were
      finally included in the mini checklist. CONCLUSIONS: An assessment of guideline
      quality can be based on a few very important key questions, and it would be
      reasonable for clinicians to do so. This could promote wider acceptance of
      guidelines in general practice and hospitals.

PMID- 25066350
TI  - [Certification of healthcare centres: Taking stock].
AB  - Healthcare facilities can use certificates to position themselves as experts to
      their clients and to distinguish themselves from their competitors. Different
      AWMF societies have addressed this topic und offer healthcare facilities the
      chance to get certified as a centre. In the course of this the societies develop
      curricula. Certification according to these curricula is then performed by the
      healthcare facilities or by an accredited agency. The different certificates show
      large differences in their certification requirements, which makes comparing them
      difficult. The present publication provides an overview of societies addressing
      certification and centres that are currently being certified. 

PMID- 25066351
TI  - [Marketing approval and market surveillance of medical devices in Germany: Where
      does policy integration take place?].
AB  - Since 2011 new regulatory measures regarding medical devices have been set up
      with the aim to eliminate obstacles to innovations and to find more coordinated
      ways to marketing authorisation and market surveillance. This essay investigates
      whether these new and existing coordination mechanisms build up to a Joined-up
      Government approach. The analysis shows that the regulatory process should be
      adjusted along several dimensions. First, many organisations lack awareness
      regarding their stakeholders and focus solely on their immediate organisational
      activities. Second, the regulatory process (marketing authorisation and market
      surveillance) is too fragmented for an effective communication to take place.
      Finally, the underlying strategy process is an ad-hoc approach lacking continuity
      and continued involvement of, in particular, the responsible federal ministries. 

PMID- 25066352
TI  - [SR/PS-method for using data of primary studies from systematic reviews in the
      evaluation of health technologies].
AB  - In general, the evaluation of health technologies is a time-consuming process
      being performed on the basis of systematic reviews of clinical (primary) studies.
      In order to save time, health technologies may be assessed based on previously
      published systematic reviews. However, this assessment method can be associated
      with a high risk of bias of the obtained results. We developed, therefore, the
      "Systematic Reviews for assessment based on Primary Studies" (SR/PS) method to
      enable a transparent, valid and time-saving evaluation of the technologies. Using
      the SR/PS method the evaluation of the hits that were identified through the
      literature search for systematic reviews and, if appropriate, through additional
      search for primary studies is being performed in three stages, namely
      identification, quality assessment and information synthesis. This process
      results in the ascertainment of the three most important sets of information: the
      pool of identified studies, the pool of methodologically sound studies and the
      results of the information synthesis. Each stage of the evaluation comprises the
      comprehensive use of relevant data on primary studies from the systematic
      reviews. At each stage, the corresponding systematic reviews will be selected
      from the identified hits using certain quality criteria. If information obtained
      from the systematic reviews is insufficient it will be completed by additionally
      incorporating the primary studies. The SR/PS method can be especially helpful in
      performing projects with many primary studies (e. g., guidelines development). 

PMID- 25066353
TI  - [GRADE guidelines: 13. Preparing Summary of Findings tables and evidence profiles
      - continuous outcomes].
AB  - Presenting continuous outcomes in Summary of Findings tables presents particular
      challenges to interpretation. When each study uses the same outcome measure, and
      the units of that measure are intuitively interpretable (e.g., duration of
      hospitalisation, duration of symptoms), presenting differences in means is
      usually desirable. When the natural units of the outcome measure are not easily
      interpretable, choosing a threshold to create a binary outcome and presenting
      relative and absolute effects become a more attractive alternative. When studies
      use different measures of the same construct, calculating summary measures
      requires converting to the same units of measurement for each study. The longest
      standing and most widely used approach is to divide the difference in means in
      each study by its standard deviation and present pooled results in standard
      deviation units (standardised mean difference). Disadvantages of this approach
      include vulnerability to varying degrees of heterogeneity in the underlying
      populations and difficulties in interpretation. Alternatives include presenting
      results in the units of the most popular or interpretable measure, converting to
      dichotomous measures and presenting relative and absolute effects, presenting the
      ratio of the means of intervention and control groups, and presenting the results
      in minimally important difference units. We outline the merits and limitations of
      each alternative and provide guidance for meta-analysts and guideline developers.
      KEY POINTS: Summary of Findings tables provide succinct presentations of evidence
      quality and magnitude of effects. Summarising the findings of continuous outcomes
      presents special challenges to interpretation that become daunting when
      individual trials use different measures for the same construct. The most
      commonly used approach to providing pooled estimates for different measures,
      presenting results in standard deviation units, has limitations related to both
      statistical properties and interpretability. Potentially preferable alternatives
      include presenting results in the natural units of the most popular measure,
      transforming into a binary outcome and presenting relative and absolute effects,
      presenting the ratio of the means of intervention and control groups, and
      presenting results in preestablished minimally important difference units.

PMID- 25066354
TI  - Extremely low frequency electromagnetic field exposure causes cognitive
      impairment associated with alteration of the glutamate level, MAPK pathway
      activation and decreased CREB phosphorylation in mice hippocampus: reversal by
      procyanidins extracted from the lotus seedpod.
AB  - Lotus seedpod procyanidins (LSPCs) could effectively prevent learning and memory
      damage and oxidative damage caused by extremely low frequency electromagnetic
      field (ELF-EMF) exposure. However, LSPCs protect neurons from ELF-EMF-induced
      damage by mechanisms currently not clear. An excessive release of glutamate is
      considered to be one of the molecular mechanisms of neuronal damage in several
      neurological diseases. In this study we determined whether the ELF-EMF (50 Hz, 8
      mT, 28 days) exposure induced alterations of glutamate release in mice
      hippocampus and explored the possible mechanism, and if LSPC treatment normalized
      its alterations. The results showed that ELF-EMF exposure induced the increased
      contents of glutamate, GABA, excessively activated NMDA receptors, increasing the
      number of NMDA receptor 2B (NR2B) and intracellular Ca(2+) concentration
      [Ca(2+)]i in hippocampus. In addition, ELF-EMF exposure decreased the ERK1/2 and
      CREB phosphorylation, which suggested that the Ca(2+) influx induced by the ELF
      EMF exposure stimulated activity of the ERK, in turn, influences the expression
      of downstream proteins in this signaling pathway. Besides, ELF-EMF exposure also
      increased JNK1/2 phosphorylation through the activated ASK1, which plays a
      pivotal role in hippocampal neuronal cell death. However, oral administration of
      LSPCs (especially 60 and 90 mg kg(-1)) markedly improved expressions of p-CREB, p
      ERK1/2 and p-JNK1/2, accompanied by decreased levels of glutamate, GABA,
      [Ca(2+)]i and NR2B. Thus, the results from the present study suggest that p
      ERK1/2, p-JNK1/2, [Ca(2+)]i and p-CREB expression normalized, possibly via a NMDA
      receptor-channel through the changes of GABA, glutamate and NR2B, which might be
      responsible for the neuroprotective or memory enhancing effects of LSPCs. 

PMID- 25066355
TI  - Evaluation of urethral stent placement for benign urethral obstructions in dogs.
AB  - BACKGROUND: Benign urethral obstructions (BUO) in dogs result in substantial
      morbidity because of challenges with conventional therapies. Treatment of
      malignant urethral obstructions with intraluminal urethral stents is reported to
      successfully relieve obstructions. HYPOTHESIS/OBJECTIVES: To evaluate the
      efficacy and outcome of urethral stent placement for treatment of BUO in dogs.
      ANIMALS: Eleven client-owned animals with urethral stents placed for treatment of
      BUO. METHODS: Retrospective study in which medical records were reviewed in dogs
      diagnosed with BUO and treated with a metallic urethral stent. Data collected
      included signalment, cause of benign obstruction, procedure time, size and type
      of stent, complications, and short- and long-term outcome. RESULTS: Eleven dogs
      with 15 urethral stents were included. Intraluminal urethral stent(s) relieved
      the obstructions in all dogs. Four dogs had 2 stents placed in separate
      procedures because of incomplete patency after treatment (n = 1), inadvertent
      compression of the stent (n = 1), or tissue ingrowth through the stent (n = 2).
      The median continence score after stent placement was 10 of 10 (range 3-10) with
      6 dogs being continent, 3 mildly incontinent, and 1 each moderately and severely
      incontinent. All owners considered their dog to have an excellent long-term
      clinical outcome with long-term urethral patency. The median follow-up time was
      24 months (range 4-48). CONCLUSIONS AND CLINICAL IMPORTANCE: Urethral stents
      appear to be an effective treatment for benign urinary obstructions. Moderate to
      severe incontinence developed in a minority (12.5%) of dogs. Stents relieved
      obstructions in all dogs with an excellent long-term outcome.

PMID- 25066356
TI  - Left atrium and the imaging of atrial fibrosis: catch it if you can!
AB  - Atrial fibrillation is a sustained arrhythmia commonly encountered in clinical
      practice. It has a high prevalence among the elderly and contributes
      significantly to the global socio-economic burden. Among many risk factors
      predisposing to atrial fibrillation is left atrial remodelling and wall fibrosis.
      Frequently, pathological left atrial wall remodelling and fibrosis results in low
      atrial compliance and elastance significantly increase the risk of developing
      permanent atrial fibrillation. We reviewed all literature which employs imaging
      and left atrial fibrosis and we present all available imaging modalities. Current
      imaging tools may play a role in the detection of atrial fibrosis, hence
      providing valuable information for risk stratification and management of patients
      with atrial fibrillation. 

PMID- 25066357
TI  - Characterization of the near native conformational states of the SAM domain of
      Ste11 protein by NMR spectroscopy.
AB  - The sterile alpha motif or SAM domain is one of the most frequently present
      protein interaction modules with diverse functional attributions. SAM domain of
      the Ste11 protein of budding yeast plays important roles in mitogen-activated
      protein kinase cascades. In the current study, urea-induced, at subdenaturing
      concentrations, structural, and dynamical changes in the Ste11 SAM domain have
      been investigated by nuclear magnetic resonance spectroscopy. Our study revealed
      that a number of residues from Helix 1 and Helix 5 of the Ste11 SAM domain
      display plausible alternate conformational states and largest chemical shift
      perturbations at low urea concentrations. Amide proton (H/D) exchange experiments
      indicated that Helix 1, loop, and Helix 5 become more susceptible to solvent
      exchange with increased concentrations of urea. Notably, Helix 1 and Helix 5 are
      directly involved in binding interactions of the Ste11 SAM domain. Our data
      further demonstrate that the existence of alternate conformational states around
      the regions involved in dimeric interactions in native or near native conditions.

PMID- 25066358
TI  - Developing a web-based intervention to increase motivation to change and
      encourage uptake of specialist face-to-face treatment by hospital inpatients:
      change drinking.
AB  - INTRODUCTION AND AIM: Problem drinking is rarely identified unless health-care
      professionals are specifically instructed to assess alcohol consumption.
      Individualised web-based alcohol interventions provide opportunities to enhance
      screening and early identification. We aimed to create a web-based brief
      personalised feedback intervention to enable client-centred screening and self
      referral by problem drinkers recently admitted to hospital. DESIGN AND METHODS:
      To increase transparency of the development process, this short report describes
      the theoretical underpinnings and development of ChangeDrinking including
      identification of needs and matching with resources, screening tool selection,
      and look and feel. RESULTS: The website structure and content was modelled on
      motivational dialogue. ChangeDrinking is closely coupled to an independent
      questionnaire management system; this architecture enables internal logic to
      allow branching based on dynamic user inputs. The motivational underpinnings led
      to development of personalised predetermined dialogue with strong theory-practice
      links. Applying principles of conveying empathy and reflection was challenging
      within the confines of a predetermined dialogue. Reflective listening in
      ChangeDrinking does not extend to inviting statements of resistance to be
      entered. DISCUSSION AND CONCLUSIONS: ChangeDrinking has become an optional
      component of routine treatment for patients with an alcohol-related admission in
      two large UK National Health Service general hospitals.

PMID- 25066359
TI  - Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney
      disease.
AB  - AIM: The prevalence of metabolic acidosis increases as glomerular filtration rate
      falls. However, most patients with stage 4 chronic kidney disease have normal
      serum bicarbonate concentration while some with stage 3 chronic kidney disease
      have low serum bicarbonate, suggesting that other factors contribute to
      generation of acidosis. The purpose of this study is to identify risk factors,
      other than reduced glomerular filtration rate, for reduced serum bicarbonate in
      chronic kidney disease. METHODS: This is a cross-sectional analysis of baseline
      data from the Chronic Renal Insufficiency Cohort Study. Multivariable logistic
      and linear regression models were used to relate predictor variables to the odds
      of low serum bicarbonate (< 22 mM) compared with normal serum bicarbonate (22-30
      mM) and the coefficients of Delta serum bicarbonate concentration. RESULTS: The
      prevalence of low serum bicarbonate at baseline was 17.3%. Lower estimated
      glomerular filtration rate had the strongest relationship with low serum
      bicarbonate. Factors associated with higher odds of low serum bicarbonate,
      independent of estimated glomerular filtration rate, were urinary
      albumin/creatinine >= 10 mg/g, smoking, anaemia, hyperkalaemia, non-diuretic use
      and higher serum albumin. These and younger age, higher waist circumference, and
      use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers
      associated with negative Delta serum bicarbonate in linear regression models.
      CONCLUSIONS: Several factors not typically considered to associate with reduced
      serum bicarbonate in chronic kidney disease were identified including albuminuria
      >= 10 mg/g, anaemia, smoking, higher serum albumin, higher waist circumference,
      and use of angiotensin converting enzyme inhibitors or angiotensin receptor
      blockers. Future studies should explore the longitudinal effect of these factors
      on serum bicarbonate concentration.

PMID- 25066360
TI  - MK-801-induced behavioural sensitisation alters dopamine release and turnover in
      rat prefrontal cortex.
AB  - RATIONALE: Repeated exposure to psychostimulants that either increase dopamine
      (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce
      behavioural sensitisation, a phenomenon that may be important for the processes
      of addiction and even psychosis. A critical component of behavioural
      sensitisation is an increase in DA release within mesocorticolimbic circuits. In
      particular, sensitisation to amphetamine leads to increased DA release within
      well-known sub-cortical brain regions and also regulatory regions such as
      prefrontal cortex (PFC). However, it is unknown how DA release within the PFC of
      animals is altered by sensitisation to NMDA receptor antagonists. OBJECTIVES: The
      aims of the present study were twofold, firstly to examine whether a single dose
      of dizocilpine maleate (MK-801) could induce long-term behavioural sensitisation
      and secondly to examine DA release in the PFC of sensitised rats. MATERIALS AND
      METHODS: Behavioural sensitisation was assessed by measuring locomotion after
      drug exposure. DA release in the PFC was measured using freely moving
      microdialysis. RESULTS: We show that a single dose of MK-801 can induce
      sensitisation to subsequent MK-801 exposure in a high percentage of rats (66 %).
      Furthermore, rats sensitised to MK-801 have altered DA release and turnover in
      the PFC compared with non-sensitised rats. CONCLUSION: Schizophrenia patients
      have been postulated to have 'endogenous sensitisation' to psychostimulants. MK
      801-induced sensitised rats, in particular when compared with non-sensitised
      rats, provide a useful model for studying PFC dysfunction in schizophrenia.

PMID- 25066361
TI  - Morphine-induced conditioned place preference and effects of morphine pre
      exposure in adolescent and adult male C57BL/6J mice.
AB  - RATIONALE: Given the increasing abuse of prescription opioids, particularly in
      adolescents, surprisingly few preclinical studies have explored effects of
      opioids in adolescents (versus adults). OBJECTIVES: This study compared the
      conditioned rewarding effects of morphine, without (experiment 1) and with
      morphine pre-exposure (experiment 2), in adolescent and adult male mice. METHODS:
      Experiment 1: On each of three consecutive days, one of the two conditioning
      sessions was preceded by an injection of a particular dose of morphine (0.1,
      0.32, 1, 3.2, 10, 32, or 100 mg/kg, intraperitoneal) and the other by saline;
      place preference was tested on day 4. Experiment 2: Mice received once daily
      injections of saline or a particular dose of morphine (17.8 or 56 mg/kg) for 4
      days, and 3 days later, place conditioning with morphine (0.32, 1, 3.2, or 10
      mg/kg) began. RESULTS: In both experiments, morphine induced conditioned place
      preference along similar inverted U-shaped dose-response curves in adolescent and
      adult mice, with maximal effects between 0.32 and 10 mg/kg. Morphine pre-exposure
      did not sensitize morphine-induced conditioned place preference; instead,
      tolerance occurred, but only in adults. Adolescents were more sensitive than
      adults to morphine-induced locomotor stimulation. Response to novelty predicted
      the locomotor stimulating effects of morphine in adolescents, but not its
      rewarding effects. CONCLUSIONS: The rewarding effects of morphine were similar in
      adolescent and adult mice but showed differential tolerance after morphine pre
      exposure. Adolescents were more sensitive than adults to the acute locomotor
      stimulating effects of morphine, consistent with dopamine systems involved in
      locomotor activity being overactive during adolescence.

PMID- 25066362
TI  - Raw meat contaminated with epidemic clones of Burkholderia multivorans found in
      cystic fibrosis patients.

PMID- 25066363
TI  - Safety and efficacy of Creon(r) micro in children with exocrine pancreatic
      insufficiency due to cystic fibrosis.
AB  - BACKGROUND: Pancreatic enzyme replacement therapy is the foundation of
      nutritional management for exocrine pancreatic insufficiency (EPI). METHODS: A 3
      month, open-label, multicentre study in Russia assessing safety, efficacy, and
      ease-of-use of Creon((r)) Micro (5000 lipase units/spoon) in children aged 1
      month to <4 years with EPI due to cystic fibrosis. Efficacy assessments included
      growth parameters. RESULTS: All 40 subjects (mean age 26.5 months) completed
      treatment. Adverse events occurred in 40% of the subjects (most commonly
      respiratory tract infection [15%], frequent bowel movements [8%], rhinitis,
      stomatitis, nasopharyngitis, and diarrhoea [all 5%]), none were serious or led to
      discontinuation. After 3 months, mean+/-SD increases from baseline z-scores were
      height/length-for-age 0.13+/-0.48, weight-for-age 0.20+/-0.39, and BMI-for-age
      0.29+/-0.65. Treatment was rated 'easy' to administer by 95% caregivers and
      acceptance 'good'/'very good' by 90%. CONCLUSIONS: Creon Micro was well
      tolerated. Growth development parameters increased over the 3-month treatment
      period. Treatment was considered easy to use and acceptance was good.

PMID- 25066364
TI  - Highly stable, fluorescence-labeled heptapeptides substituted with a D-amino acid
      for the specific detection of oxidized low-density lipoprotein in plasma.
AB  - Probes that can detect oxidized low-density lipoprotein (ox-LDL) in plasma and in
      atherosclerotic plaques can be useful for the diagnosis, prevention, and
      treatment of atherosclerosis. Recently, we have reported that two heptapeptides
      (Lys-Trp-Tyr-Lys-Asp-Gly-Asp, KP6) coupled to fluorescein isothiocyanate (FITC)
      through the epsilon-amino group of N-terminus Lys in the absence/presence of 6
      amino-n-caproic acid (AC) linker to FITC-(FITC)KP6 and (FITC-AC)KP6-can be useful
      as fluorescent probes for the specific detection of ox-LDL. In this study, to
      develop the fluorescent peptides with high plasma stability for the specific
      detection of ox-LDL, we investigated the interaction of (FITC)KP6 and (FITC
      AC)KP6 substituted with D-Lys at the N-terminus-(FITC)dKP6 and (FITC-AC)dKP6-with
      ox-LDL, and the in vitro stability of these peptides in mouse plasma. (FITC)dKP6
      and (FITC-AC)dKP6 bound with high specificity to ox-LDL in a dose-dependent
      manner, and also to ox-LDL in the mouse plasma. Furthermore, (FITC)dKP6 was more
      stable than (FITC)KP6 in mouse plasma (102.1% versus 69.0% remained after 1 h).
      These findings strongly suggest that (FITC)dKP6 and (FITC-AC)dKP6 may be
      effective fluorescent probes with higher plasma stability than (FITC)KP6 and
      (FITC-AC)KP6 for the specific detection of ox-LDL. 

PMID- 25066365
TI  - Global biogeochemical implications of mercury discharges from rivers and sediment
      burial.
AB  - Rivers are an important source of mercury (Hg) to marine ecosystems. Based on an
      analysis of compiled observations, we estimate global present-day Hg discharges
      from rivers to ocean margins are 27 +/- 13 Mmol a(-1) (5500 +/- 2700 Mg a(-1)),
      of which 28% reaches the open ocean and the rest is deposited to ocean margin
      sediments. Globally, the source of Hg to the open ocean from rivers amounts to
      30% of atmospheric inputs. This is larger than previously estimated due to
      accounting for elevated concentrations in Asian rivers and variability in
      offshore transport across different types of estuaries. Riverine inputs of Hg to
      the North Atlantic have decreased several-fold since the 1970s while inputs to
      the North Pacific have increased. These trends have large effects on Hg
      concentrations at ocean margins but are too small in the open ocean to explain
      observed declines of seawater concentrations in the North Atlantic or increases
      in the North Pacific. Burial of Hg in ocean margin sediments represents a major
      sink in the global Hg biogeochemical cycle that has not been previously
      considered. We find that including this sink in a fully coupled global
      biogeochemical box model helps to balance the large anthropogenic release of Hg
      from commercial products recently added to global inventories. It also implies
      that legacy anthropogenic Hg can be removed from active environmental cycling on
      a faster time scale (centuries instead of millennia). Natural environmental Hg
      levels are lower than previously estimated, implying a relatively larger impact
      from human activity. 

PMID- 25066366
TI  - Age at onset, course of illness and response to psychotherapy in bipolar
      disorder: results from the Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD).
AB  - BACKGROUND: The course of bipolar disorder progressively worsens in some
      patients. Although responses to pharmacotherapy appear to diminish with greater
      chronicity, less is known about whether patients' prior courses of illness are
      related to responses to psychotherapy. METHOD: Embedded in the Systematic
      Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized
      controlled trial of psychotherapy for bipolar depression comparing the efficacy
      of intensive psychotherapy with collaborative care (a three-session psycho
      educational intervention). We assessed whether the number of previous mood
      episodes, age of illness onset, and illness duration predicted or moderated the
      likelihood of recovery and time until recovery from a depressive episode in
      patients in the two treatments. RESULTS: Independently of treatment condition,
      participants with one to nine prior depressive episodes were more likely to
      recover and had faster time to recovery than those with 20 or more prior
      depressive episodes. Participants with fewer than 20 prior manic episodes had
      faster time to recovery than those with 20 or more episodes. Longer illness
      duration predicted a longer time to recovery. Participants were more likely to
      recover in intensive psychotherapy than collaborative care if they had 10-20
      prior episodes of depression [number needed to treat (NNT) = 2.0], but equally
      likely to respond to psychotherapy and collaborative care if they had one to nine
      (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes. CONCLUSIONS: Number of
      previous mood episodes and illness duration are associated with the likelihood
      and speed of recovery among bipolar patients receiving psychosocial treatments
      for depression.

PMID- 25066368
TI  - Intussusception following rotavirus vaccination: an updated review of the
      available evidence.
AB  - In 1999, the first rotavirus vaccine licensed in the USA was withdrawn 9 months
      after introduction due to an association with intussusception that was detected
      in post-licensure surveillance. This association prompted large clinical trials
      designed to ensure the safety of two current live oral rotavirus vaccines,
      RotaTeq and Rotarix, which have since been recommended for use worldwide.
      Following their introduction, post-licensure studies have focused not only on the
      effectiveness and impact of these vaccines, but also on continued surveillance
      for intussusception. Most recent evidence from several countries shows a small
      increased risk of intussusception following vaccination with Rotarix and RotaTeq
      within the context of their demonstrated benefits. This review summarizes the
      available data on the safety of rotavirus vaccines with regards to
      intussusception. 

PMID- 25066367
TI  - Prevalence of Vibrio parahaemolyticus, and Vibrio vulnificus in blue crabs
      (Callinectes sapidus), seawater and sediments of the Maryland Coastal Bays.
AB  - AIMS: To determine the prevalence of total and pathogenic Vibrio parahaemolyticus
      (Vp) and V. vulnificus (Vv) in blue crabs, water and sediment from the Maryland
      Coastal Bays (MCBs), USA. METHODS AND RESULTS: Crab, haemolymph, sediment and
      seawater samples were collected monthly from four sites in MCBs from February
      2012 through October 2012 with environmental parameters recorded. The most
      probable-number (MPN) methodology was used to enumerate Vp and Vv with
      presumptive colonies and the presence of virulence markers confirmed using
      polymerase chain reaction (PCR). Results indicate that blue crabs contained both
      Vp and Vv at densities (7.28 and 5.43 log MPN g(-1) , respectively) higher than
      those reported for bivalves. In addition, markers for clinically relevant strains
      of both species were detected in over 30% of samples. Haemolymph, sediment and
      seawater samples were also routinely positive for both species and clinically
      relevant strains, but generally at lower densities than found in crabs (4.27,
      3.28, and 2.39 log MPN g(-1) per ml(-1) Vp, and 4.28, 2.49 and 2.38 log MPN g(-1)
      per ml(-1) Vv). CONCLUSIONS: Blue crabs concentrate Vp and Vv at levels greater
      than found in water or sediment. While changes in abundance associated with
      temperature are apparent, there is little evidence to support differences among
      sampling locations. SIGNIFICANCE AND IMPACT OF THE STUDY: These results highlight
      the potential for blue crab related vibriosis and the importance of proper
      handling, cooking and care of this popular seafood before consumption.

PMID- 25066369
TI  - Unconventional pore and defect generation in molybdenum disulfide: application in
      high-rate lithium-ion batteries and the hydrogen evolution reaction.
AB  - A 2H-MoS2 (H=hexagonal) ultrathin nanomesh with high defect generation and large
      porosity is demonstrated to improving electrochemical performance, including in
      lithium-ion batteries (LIBs) and the hydrogen evolution reaction (HER), with the
      aid of a 3D reduced graphene oxide (RGO) scaffold as fast electron and ion
      channels. The 3D defect-rich MoS2 nanomesh/RGO foam (Dr-MoS2 Nm/RGO) can be
      easily obtained through a one-pot cobalt acetate/graphene oxide (GO) co-assisted
      hydrothermal reaction, in which GO, cobalt and acetate ions are co-morphology
      controlling agents and defect inducers. As an anode material for LIBs, Dr-MoS2
      Nm/RGO has only a 9% capacity decay at a 10 C discharge rate versus 0.2 C with
      stable cyclability at the optimized composition (5 wt% RGO to MoS2 and 2 mol% Co
      to Mo), and significantly achieves 810 mA h g(-1) at a high current density of
      9.46 A g(-1) over at least 150 cycles. Moreover, Dr-MoS2 Nm/RGO exhibits superior
      activity for the HER with an overpotential as low as 80 mV and a Tafel slope of
      about 36 mV per decade. In contrast to the MoS2 nanosheet/RGO (MoS2 Ns/RGO),
      which is synthesized in the absence of cobalt ions, Dr-MoS2 Nm/RGO provides high
      interconnectivity for efficient lithium-ion transport, and rich defects as
      electrochemically active sites. DFT is used to prove the existence of rich
      defects due to anion replacement to become a Co-Mo-S atomic structure, releasing
      inert basal planes to active sites.

PMID- 25066370
TI  - Second-trimester maternal distress increases the risk of small for gestational
      age.
AB  - BACKGROUND: The effect of prenatal distress on the risk of a small for
      gestational age (SGA) infant is uncertain. We have addressed the influences of
      prenatal stress, anxiety and depression on the risk of SGA. We also examined the
      effects of infant sex and timing of distress during pregnancy on any observed
      associations. METHOD: The study population comprised 5606 healthy nulliparous
      pregnant women who participated in the international prospective Screening for
      Obstetric and Pregnancy Endpoints (SCOPE) study. Women completed the Perceived
      Stress Scale (PSS), the short form of the Spielberger State-Trait Anxiety
      Inventory (STAI) and the Edinburgh Postnatal Depression Scale (EPDS) at 15 +/- 1
      and 20 +/- 1 weeks' gestation. SGA was defined as birthweight below the 10th
      customized percentile. Logistic regression was used for data analysis, adjusting
      for several potential confounders such as maternal age, body mass index (BMI),
      smoking, socio-economic status and physical exercise. RESULTS: The risk of SGA
      was increased in relation to mild [adjusted odds ratio (aOR) 1.35, 95% confidence
      interval (CI) 1.07-1.71], moderate (aOR 1.26, 95% CI 1.06-1.49), high (aOR 1.45,
      95% CI 1.08-1.95) and very high stress scores (aOR 1.56, 95% CI 1.03-2.37); very
      high anxiety score (aOR 1.45, 95% CI 1.13-1.86); and very high depression score
      (aOR 1.14, 95% CI 1.05-1.24) at 20 +/- 1 weeks' gestation. Sensitivity analyses
      showed that very high anxiety and very high depression increases the risk of SGA
      in males but not in females whereas stress increases the risk of SGA in both
      males and females. CONCLUSIONS: These findings suggest that prenatal stress,
      anxiety and depression measured at 20 weeks' gestation increase the risk of SGA.
      The effects of maternal anxiety and depression on SGA were strongest in male
      infants.

PMID- 25066371
TI  - Rapid and robust pulmonary proton ZTE imaging in the mouse.
AB  - Pulmonary MRI is challenging because of the low proton density and rapid
      transverse relaxation in the lung associated with microscopic magnetic field
      inhomogeneities caused by tissue-air interfaces. Therefore, low signal is
      obtained in gradient and spin echo proton images. Alternatively, non-proton MRI
      using hyperpolarized gases or radial techniques with ultrashort or zero TE have
      been proposed to image the lung. Also with the latter approach, the general
      challenge remains to provide full coverage of the lung at sufficient spatial
      resolution, signal-to-noise ratio (SNR) and image quality within a reasonable
      scan time. This task is further aggravated by physiological motion and is
      particularly demanding in small animals, such as mice. In this work, three
      dimensional (3D) zero echo time (ZTE) imaging is employed for efficient pulmonary
      MRI. Four protocols with different averaging and respiratory triggering schemes
      are developed and compared with respect to image quality and SNR. To address the
      critical issue of background signal in ZTE images, a subtraction approach is
      proposed, providing images virtually free of disturbing signal from nearby
      hardware parts. The protocols are tested for pulmonary MRI in six mice at 4.7 T,
      consistently providing images of high quality with a 3D isotropic resolution of
      313 um and SNR values in the lung between 8.0 and 18.5 within scan times between
      1 min 21 s and 4 min 44 s. A generally high robustness of the ZTE approach
      against motion is observed, whilst respiratory triggering further improves the
      SNR and visibility of image details. The developed techniques are expected to
      enable efficient preclinical animal studies in the lung and will also be of
      importance for human applications. Further improvements are expected from
      radiofrequency (RF) coils with increased SNR and reduced background signal.

PMID- 25066372
TI  - Animal models of dementia and cognitive dysfunction.
AB  - Recent advances in the understanding of the pathophysiological mechanisms
      underlying Alzheimer's disease and other cognitive deficits have pointed to novel
      strategies for drug development. Animal models have contributed noticeably to
      these advances and are an indispensible part in the evaluation of therapeutics.
      This review is an exhaustive study of animal models of dementia and cognitive
      dysfunction. A thorough and critical evaluation of current rodent models of
      dementia, and discussion about their role in drug discovery and development have
      been carried out. Since dementia has multiple pathophysiological mechanisms, we
      have tried to provide a detailed description of various types of animal models
      which would depict different pathophysiological stages and causes of dementia.
      This review aims to better understand the prognosis, biochemical, and behavioral
      alterations that occur during dementia and hence facilitate drug discovery and
      development. 

PMID- 25066373
TI  - Prevalence of alcohol-related pathologies at autopsy: Estonian Forensic Study of
      Alcohol and Premature Death.
AB  - AIMS: Alcohol can induce diverse serious pathologies, yet this complexity may be
      obscured when alcohol-related deaths are classified according to a single
      underlying cause. We sought to quantify this issue and its implications for
      analysing mortality data. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study
      included 554 men aged 25-54 in Estonia undergoing forensic autopsy in 2008-09.
      MEASUREMENTS: Potentially alcohol-related pathologies were identified following
      macroscopic and histological examination. Alcohol biomarkers levels were
      determined. For a subset (26%), drinking behaviour was provided by next-of-kin.
      The Estonian Statistics Office provided underlying cause of death. FINDINGS: Most
      deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32%
      had pathologies in two or more organs. The liver was most commonly affected
      [60.5%, 95% confidence interval (CI) = 56.3-64.6] followed by the lungs (18.6%,
      95% CI = 15.4-22.1), stomach (17.5%, 95% CI = 14.4-20.9), pancreas (14.1%, 95% CI
      = 11.3-17.3), heart (4.9%, 95% CI = 3.2-7.0) and oesophagus (1.4%, 95% CI = 0.6
      2.8). Only a minority with liver pathology had a second pathology. The number of
      pathologies correlated with alcohol biomarkers (phosphatidylethanol, gamma
      glytamyl transpeptidase in blood, ethylglucuronide, ethylsulphate in urine).
      Despite the high prevalence of liver pathology, few deaths had alcoholic liver
      disease specified as the underlying cause. CONCLUSION: The majority of 554 men
      aged 25-54 undergoing forensic autopsy in Estonia in 2008-09 showed evidence of
      alcohol-related pathology. However, the recording of deaths by underlying cause
      failed to capture the scale and nature of alcohol-induced pathologies found.

PMID- 25066375
TI  - How does burnout affect physician productivity? A systematic literature review.
AB  - BACKGROUND: Interest in the well-being of physicians has increased because of
      their contributions to the healthcare system quality. There is growing
      recognition that physicians are exposed to workplace factors that increase the
      risk of work stress. Long-term exposure to high work stress can result in
      burnout. Reports from around the world suggest that about one-third to one-half
      of physicians experience burnout. Understanding the outcomes associated with
      burnout is critical to understanding its affects on the healthcare system.
      Productivity outcomes are among those that could have the most immediate effects
      on the healthcare system. This systematic literature review is one of the first
      to explore the evidence for the types of physician productivity outcomes
      associated with physician burnout. It answers the question, "How does burnout
      affect physician productivity?" METHODS: A systematic search was performed of:
      Medline Current, Medline in process, PsycInfo, Embase and Web of Science. The
      search period covered 2002 to 2012. The searches identified articles about
      practicing physicians working in civilian settings. Articles that primarily
      looked only at residents or medical students were excluded. Productivity was
      captured by hours worked, patients seen, sick leave, leaving the profession,
      retirement, workload and presenteeism. Studies also were excluded if: (1) the
      study sample was not comprised of at least 50% physicians, (2) the study did not
      examine the relationship between burnout and productivity or (3) a validated
      measure of burnout was not used. RESULTS: The search identified 870 unique
      citations; 5 met the inclusion/exclusion criteria. This review indicates that
      globally there is recognition of the potential impact of physician burnout on
      productivity. Productivity was examined using: number of sick leave days, work
      ability, intent to either continue practicing or change jobs. The majority of the
      studies indicate there is a negative relationship between burnout and
      productivity. However, there is variation depending on the type of productivity
      outcome examined. CONCLUSIONS: There is evidence that burnout is associated with
      decreased productivity. However, this line of inquiry is still developing. A
      number of gaps are yet to be filled including understanding how to quantify the
      changes in productivity related to burnout.

PMID- 25066376
TI  - Child sexual abuse in Turkey: an analysis of 1002 cases.
AB  - This study investigated the characteristics of abuse suffered by children, the
      dimensions of the psychiatric effects associated with abuse, and the factors
      affecting these. One thousand two cases aged under 18, exposed to sexual abuse,
      and referred over a 7-year period were assessed. Girls represented 80.8% of
      cases, and the numbers rose with age. The aggressors were all male, and 88.2%
      were known to their victim. Approximately half the children were exposed to
      sexual abuse involving penetration. Psychological pathology was identified in
      62.1%. Female gender, the presence of penetration, physical violence, and incest
      significantly increased the development of psychological pathology. Levels of
      awareness in people close to and trusted by the child must be raised to minimize
      the adverse effects of trauma in the long term, preventive measures must be
      taken, and medical and social support units from which victims can receive
      assistance need to be established. 

PMID- 25066374
TI  - A GAPDH-mediated trans-nitrosylation pathway is required for feedback inhibition
      of bile salt synthesis in rat liver.
AB  - BACKGROUND & AIMS: Bile salts inhibit their own production by inducing the
      nuclear receptor small heterodimer partner (SHP) (encoded by NR0B2), which
      contributes to repression of the gene encoding cholesterol 7alpha-hydroxylase
      (CYP7A1), a key enzyme for the control of bile salt synthesis. On the other hand,
      bile salts stimulate hepatic synthesis of nitric oxide. We investigated the role
      of nitric oxide signaling in the control of CYP7A1 expression and the involvement
      in this process of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which
      participates in intracellular propagation of nitric oxide signals. METHODS: We
      studied the effects of inhibitors of nitric oxide synthesis (L-NG-nitroarginine
      methyl ester [L-NAME]) or protein nitrosylation (via dithiothreitol) on bile salt
      homeostasis in male Wistar rats placed on a cholate-rich diet for 5 days and in
      cultured primary hepatocytes. S-nitrosylation of GAPDH was assessed using a
      biotin-switch assay. Interacions of SHP with other proteins and with the Cyp7a1
      promoter sequence were studied using immunoprecipitation and chromatin
      immunoprecipitation (ChIP) assays. We reduced the GAPDH levels in H35 cells with
      small interfering RNAs. GAPDH nitrosylation was assessed in normal and
      cholestatic rat and human livers. RESULTS: Rats placed on cholate-rich diets and
      given L-NAME had increased intrahepatic and biliary levels of bile salts, and
      deficiency in repression of CYP7A1 (at the messenger RNA and protein levels) in
      liver tissue, despite preserved induction of SHP. In cultured hepatocytes, L-NAME
      or dithiothreitol blocked cholate-induced down-regulation of CYP7A1 without
      impairing SHP up-regulation. In hepatocytes, cholate promoted S-nitrosylation of
      GAPDH and its translocation to the nucleus, accompanied by S-nitrosylation of
      histone deacetylase 2 (HDAC2) and Sirtuin 1 (SIRT1), deacetylases that
      participate, respectively, in the formation of Cyp7a1 and Shp repressor
      complexes. Knockdown of GAPDH prevented repression of CYP7A1 by cholate, and
      blocking nuclear transport of nitrosylated GAPDH reduced cholate-induced
      nitrosylation of HDAC2 and SIRT1; this effect was accompanied by abrogation of
      Cyp7a1 repression. Cholate induced binding of SHP to HDAC2 and its recruitment to
      the Cyp7a1 promoter; these processes were inhibited by blocking nitric oxide
      synthesis. Levels of nitrosylated GAPDH and nitrosylated HDAC2 were increased in
      cholestatic human and rat livers reflecting increased concentrations of bile
      salts in these conditions. CONCLUSIONS: In rat liver, excess levels of bile salts
      activate a GAPDH-mediated transnitrosylation cascade that provides feedback
      inhibition of bile salt synthesis.

PMID- 25066377
TI  - Skin sparing mastectomy: technique and suggested methods of reconstruction.
AB  - AIM: To demonstrate the feasibility and accessibility of performing adequate
      mastectomy to extirpate the breast tissue, along with en-block formal axillary
      dissection performed from within the same incision. We also compared different
      methods of immediate breast reconstruction used to fill the skin envelope to
      achieve the best aesthetic results. METHODS: 38 patients with breast cancer
      underwent skin-sparing mastectomy with formal axillary clearance, through a
      circum-areolar incision. Immediate breast reconstruction was performed using
      different techniques to fill in the skin envelope. Two reconstruction groups were
      assigned; group 1: Autologus tissue transfer only (n=24), and group 2: implant
      augmentation (n=14). AUTOLOGUS TISSUE TRANSFER: The techniques used included
      filling in the skin envelope using Extended Latissimus Dorsi flap (18 patients)
      and Pedicled TRAM flap (6 patients). AUGMENTATION WITH IMPLANTS: Subpectoral
      implants(4 patients), a rounded implant placed under the pectoralis major muscle
      to augment an LD reconstructed breast. LD pocket (10 patients), an anatomical
      implant placed over the pectoralis major muscle within a pocket created by the LD
      flap. No contra-lateral procedure was performed in any of the cases to achieve
      symmetry. RESULTS: All cases underwent adequate excision of the breast tissue
      along with en-block complete axillary clearance (when indicated), without the
      need for an additional axillary incision. Eighteen patients underwent
      reconstruction using extended LD flaps only, six had TRAM flaps, four had
      augmentation using implants placed below the pectoralis muscle along with LD
      flaps, and ten had implants placed within the LD pocket. Breast shape, volume and
      contour were successfully restored in all patients. Adequate degree of ptosis was
      achieved, to ensure maximal symmetry. CONCLUSIONS: Skin Sparing mastectomy
      through a circum-areolar incision has proven to be a safe and feasible option for
      the management of breast cancer in Egyptian women, offering them adequate
      oncologic control and optimum cosmetic outcome through preservation of the skin
      envelope of the breast when ever indicated. Our patients can benefit from safe
      surgery and have good cosmetic outcomeby applying different reconstructive
      techniques.

PMID- 25066378
TI  - Patterns of somatic alterations between matched primary and metastatic colorectal
      tumors characterized by whole-genome sequencing.
AB  - Colorectal cancer (CRC) patients have poor prognosis after formation of distant
      metastasis. Understanding the molecular mechanisms by which genetic changes
      facilitate metastasis is critical for the development of targeted therapeutic
      strategies aimed at controlling disease progression while minimizing toxic side
      effects. A comprehensive portrait of somatic alterations in CRC and the changes
      between primary and metastatic tumors has yet to be developed. We performed whole
      genome sequencing of two primary CRC tumors and their matched liver metastases.
      By comparing to matched germline DNA, we catalogued somatic alterations at
      multiple scales, including single nucleotide variations, small insertions and
      deletions, copy number aberrations and structural variations in both the primary
      and matched metastasis. We found that the majority of these somatic alterations
      are present in both sites. Despite the overall similarity, several de novo
      alterations in the metastases were predicted to be deleterious, in genes
      including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and
      progression of distant metastasis. Through careful examination of the mutation
      prevalence among tumor cells at each site, we also proposed distinct clonal
      evolution patterns between primary and metastatic tumors in the two cases. These
      results suggest that somatic alterations may play an important role in driving
      the development of colorectal cancer metastasis and present challenges and
      opportunities when considering the choice of treatment.

PMID- 25066379
TI  - Analysis of chromosomal structural variation in patients with congenital left
      sided cardiac lesions.
AB  - BACKGROUND: We sought to characterize the landscape of structural variation
      associated with the subset of congenital cardiac defects characterized by left
      sided obstruction. METHODS: Cases with left-sided cardiac defects (LSCD) and
      pediatric controls were uniformly genotyped and assessed for copy number variant
      (CNV) calls. Significance testing was performed to ascertain differences in
      overall CNV incidence, and for CNV enrichment of specific genes and gene
      functions in LSCD cases relative to controls. RESULTS: A total of 257 cases of
      European descent and 962 ethnically matched, disease-free pediatric controls were
      included. Although there was no difference in CNV rate between cases and
      controls, a significant enrichment in rare LSCD CNVs was detected overall (p=7.30
      * 10(-3) , case/control ratio=1.26) and when restricted either to deletions
      (p=7.58 * 10(-3) , case/control ratio=1.20) or duplications (3.02 * 10(-3) ,
      case/control ratio=1.43). Neither gene-based, functional nor knowledge-based
      analyses identified genes, loci or pathways that were significantly enriched in
      cases as compared to controls when appropriate corrections for multiple tests
      were applied. However, several genes of interest were identified by virtue of
      their association with cardiac development, known human conditions, or reported
      disruption by CNVs in other patient cohorts. CONCLUSION: This study examines the
      largest cohort to date with LSCD for structural variation. These data suggest
      that CNVs play a role in disease risk and identify numerous genes disrupted by
      CNVs of potential disease relevance. These findings further highlight the genetic
      heterogeneity and complexity of these disorders.

PMID- 25066380
TI  - [Differentiation of Mycobacterium fortuitum complex species using mass
      spectrometry].

PMID- 25066381
TI  - [Characteristics of tuberculosis in the immigrant population in South Granada
      Health Area].
AB  - INTRODUCTION: The incidence of tuberculosis (TB) among the native population in
      Spain continues to decrease, resulting in a higher proportion of foreign-born
      cases. The aim of this study was to identify the differential TB characteristics
      within the immigrant population with respect to the native population in the
      South Granada Health Area, Spain. METHODS: This was a descriptive study,
      including all cases of TB diagnosed during the period 2003-2010. Cases were
      identified through a prospective database. A logistic regression analysis was
      performed to determine differential characteristics. RESULTS: From 319 TB cases
      diagnosed, 247 were natives and 72 (22.6%) immigrants, and 272 were pulmonary
      tuberculosis. The following variables were significantly associated with
      immigrant TB cases: age<35 years (OR=4.75, CI: 2.72-8.31), higher percentage of
      cavitated chest X-ray (OR=2.26, CI: 1.20-4.20), higher percentage of smear
      positive cases (OR=1.80, CI: 1.02-3.16), longer diagnostic delay in smear
      positive pulmonary TB (median 32 days vs. 21 days P=.043), and lower total
      lethality (OR=0.12; CI: 0.01-0.89). CONCLUSIONS: The incidence of TB has remained
      constant in the South Granada Health Area due to the increase in cases among
      immigrants. Compared with native TB patients, immigrant patients were younger and
      had more advanced disease (higher percentage of smear-positive cases and higher
      percentage of cavitated chest X-ray) and longer diagnostic delay in smear
      positive pulmonary TB, indicating poorer TB control. Strategies for earlier
      diagnosis of TB in immigrants are essential.

PMID- 25066382
TI  - Training should be the first step toward an antifungal stewardship program.
AB  - The frequency of use of systemic antifungal agents has increased significantly in
      most tertiary centers. However, antifungal stewardship has received very little
      attention. The objective of this article was to assess the knowledge of
      prescribing physicians in our institution as a first step in the development of
      an antifungal stewardship program. Attending physicians from the departments that
      prescribe most antifungals were invited to complete a questionnaire based on
      current guidelines on diagnosis and therapy of invasive candidiasis and invasive
      aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians
      who were invited to participate. The physicians belonged to the following
      departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical
      (5.5%). The mean (+/-SD) score of correct responses was 5.16+/-1.73. In the case
      of candidiasis, only 55% of the physicians clearly distinguished between
      colonization and infection, and 17.5% knew the local rate of fluconazole
      resistance. Thirty-three percent knew the accepted indications for antifungal
      prophylaxis, and 23% the indications for empirical therapy. However, most
      physicians knew which antifungals to choose when starting empirical therapy
      (73.5%). As for aspergillosis, most physicians (67%) could differentiate between
      colonization and infection, and 34.5% knew the diagnostic value of galactomannan.
      The radiological features of IA were well recognized by 64%, but only 31.5% were
      aware of the first line of treatment for IA, and 36% of the recommended duration
      of therapy. The usefulness of antifungal levels was known by 67%. This simple,
      easily completed questionnaire enabled us to identify which areas of our training
      strategy could be improved. 

PMID- 25066383
TI  - Mapping polyamide-DNA interactions in human cells reveals a new design strategy
      for effective targeting of genomic sites.
AB  - Targeting the genome with sequence-specific synthetic molecules is a major goal
      at the interface of chemistry, biology, and personalized medicine.
      Pyrrole/imidazole-based polyamides can be rationally designed to target specific
      DNA sequences with exquisite precision in vitro; yet, the biological outcomes are
      often difficult to interpret using current models of binding energetics. To
      directly identify the binding sites of polyamides across the genome, we designed,
      synthesized, and tested polyamide derivatives that enabled covalent crosslinking
      and localization of polyamide-DNA interaction sites in live human cells.
      Bioinformatic analysis of the data reveals that clustered binding sites, spanning
      a broad range of affinities, best predict occupancy in cells. In contrast to the
      prevailing paradigm of targeting single high-affinity sites, our results point to
      a new design principle to deploy polyamides and perhaps other synthetic molecules
      to effectively target desired genomic sites in vivo. 

PMID- 25066384
TI  - Initial presentations and final outcomes of primary pyogenic liver abscess: a
      cross-sectional study.
AB  - BACKGROUND: Although pyogenic liver abscess (PPLA) fatalities are decreasing
      owing to early diagnosis and effective treatments, PPLA-associated complications
      still exist. The purpose of this study was to analyze the characteristic features
      of initial presentations and final outcomes of PPLA caused by different
      pathogens. METHODS: This retrospective study collected and analyzed information
      regarding initial presentations and final outcomes in patients diagnosed with
      PPLA at admitted at Changhua Christian Hospital from January 1 to December 31,
      2010. RESULTS: During the study period, we analyzed the records of a total of 134
      patients with documented PPLA. There were no significant causative pathogen
      related differences in symptoms at initial presentation. Compared with the
      survivor group, patients in the mortality group were characterized by male gender
      (p < 0.001), malignancy (p < 0.001), respiratory distress (p =0.007), low blood
      pressure (p = 0.024), jaundice (p = < 0.001), rupture of liver abscess (p <
      0.001), endophthalmitis (p = 0.003), and multiple organ failure (p < 0.001). No
      patients received liver transplantation or were diagnosed with HIV during the
      study period. According to univariate logistic regression analysis, gender (OR =
      1.185, 95% CI: 0.284-11.130, p = 0.006), malignancy (OR = 2.067, 95% CI: 1.174
      13.130, p = 0.004), respiratory distress (OR = 1.667, 95% CI: 1.164-14.210, p =
      0.006), low blood pressure (OR = 2.167, 95% CI: 2.104-13.150, p = 0.003),
      jaundice (OR = 1.9, 95% CI: 1.246-3.297, p = 0.008), rupture of liver abscess (OR
      = 5.167, 95% CI: 2.194-23.150, p = 0.003), endophthalmitis (OR = 2.167, 95% CI:
      1.234-13.140, p = 0.005), and multiple organ failure (OR = 3.067, 95% CI: 1.184
      15.150, p = 0.001) differed significantly between the mortality and survivor
      groups. CONCLUSION: Although the initial presentations of PPLA caused by
      different pathogens were similar, there were significant differences in mortality
      in cases involving: (1) male patients, (2) malignancy, (3) initial respiratory
      distress, (4) initial low blood pressure, (5) jaundice, (6) rupture of liver
      abscess, (7) endophthalmitis, , and (8) multiple organ failure. We strongly
      recommend using a severity score of the disease to determine the risk of
      mortality for each patient with PPLA. In order to prevent complications and
      reduce mortality, more attention must be paid to high-risk PPLA patients.

PMID- 25066385
TI  - Pharmacokinetics and pharmacodynamics of xylazine administered by the intravenous
      or intra-osseous route in adult horses.
AB  - In certain situations, an alternate route for parenteral drug administration in
      horses may be useful. The intra-osseous (IO) route may provide a safe alternative
      to the intravenous (i.v.) route for administration of sedatives to horses when
      the i.v. route is inaccessible or undesirable. Six adult horses were administered
      xylazine i.v. or IO in a block-randomized crossover design. For the i.v. trial,
      both jugular veins were catheterized, and one was used for xylazine
      administration, while the other was used for blood collection. For the IO trial,
      one jugular vein was catheterized for blood collection and an intra-osseous
      device was placed in the tuber coxae using a powered driver for xylazine
      administration. Heart rate, respiratory rate, and head position were measured,
      and concentration of sedation was assessed at various times up to 90 min.
      Xylazine concentrations were measured using high-performance liquid
      chromatography and noncompartmental analysis was performed. General linear mixed
      modeling and Wilcoxon signed-rank tests were used for statistical analysis, with
      P <= 0.05. There were no significant differences in heart rate, respiratory rate,
      head position, concentration of sedation, Cmax , Tmax , half-life, or AUC between
      the i.v. and the IO routes of drug administration. No complications were observed
      following placement of the intra-osseous device. Intra-osseous xylazine
      administration provides a useful option in emergent and other settings in which
      i.v. access is difficult or contraindicated. 

PMID- 25066386
TI  - Influence of procedural variables on rat inhibitory avoidance and escape
      behaviors generated by the elevated T-maze.
AB  - A wealth of evidence indicates that changes in procedural parameters and/or
      environmental conditions may exert a remarkable influence on the basal expression
      of defensive behaviors in different animal tests of anxiety. The goal of the
      current study was to further investigate the influence of procedural factors upon
      inhibitory avoidance acquisition and escape expression of male Wistar rats
      exposed to the elevated T-maze. These responses have been related in terms of
      psychopathology to generalized anxiety and panic disorders, respectively. Our
      results showed that the expression of these behaviors is not affected by prior
      handling of the animals or by increasing the illumination level of the
      experimental room from 60 to 580lx. They also showed that enhancing the number of
      avoidance trials from 3 to 6 favors the acquisition of this behavior. Under this
      condition, both diazepam (2mg/kg) and clonazepam (1-4mg/kg) caused anxiolytic
      effects, but only the latter benzodiazepine impaired escape expression, a
      panicolytic-like effect. In animals exposed to the elevated T-maze whole
      apparatus 24h before the test, the anxiolytic effect of these drugs was canceled
      out, which is consistent with the one-trial tolerance phenomenon widely observed
      in the elevated plus-maze. This procedure, however, does not interfere with the
      anti-escape effect caused by clonazepam. These results suggest that a 6-trial
      avoidance learning protocol may be a useful measure for compensating possible
      individual differences in the acquisition of this defensive response and to
      improve drug detection in the test. 

PMID- 25066387
TI  - Immunogenicity, safety and tolerability of a bivalent human papillomavirus
      vaccine in adolescents with juvenile idiopathic arthritis.
AB  - AIMS: To evaluate the immunogenicity, safety and tolerability of the bivalent HPV
      vaccine in female patients with juvenile idiopathic arthritis (JIA). METHODS:
      Twenty-one patients with JIA aged 12-25 years and 21 healthy controls were
      enrolled and received three doses of the bivalent HPV vaccine. RESULTS: All of
      the subjects were seronegative at baseline and seroconverted after the scheduled
      doses. The JIA patients showed significantly lower HPV16 neutralising antibody
      titres than controls 1 month after the administration of the third dose (p <
      0.05), whereas no significant difference was observed in HPV18 neutralising
      antibody titres. Local and systemic reactions were similarly frequent in the
      patients and controls, and there were no significant changes in 27-joint juvenile
      arthritis disease activity score or laboratory tests. CONCLUSION: The bivalent
      HPV vaccine is safe in patients with stable JIA and regardless of the use of
      medications the vaccine assures an adequate degree of protection for a certain
      time.

PMID- 25066388
TI  - Pathways of fear and anxiety in endodontic patients.
AB  - AIM: To evaluate the most common pathways of fear and anxiety in patients who
      have had root canal treatment or are planned to have one. METHODOLOGY: Six
      hundred and twenty-seven patients were approached to participate, of which five
      hundred and ninety-four patients (20-90 years) accepted. All consenting patients
      had a root filling or were treatment planned to have one. The survey by Ost &
      Hugdahl () on anxiety response patterns was modified and used. Data were
      presented using descriptive statistics, tested for normality using the Kolmogorov
      Smirnov test and analysed with nonparametric anova (Kruskal-Wallis) and post hoc
      test. RESULTS: Cognitive conditioning and parental pathways seem to be the
      primary cause (P < 0.05) of fear and anxiety with root canal treatment. Females
      were significantly more likely to be influenced by indirect conditioned
      experiences such as informative, parental, verbal threat and vicarious pathways.
      CONCLUSION: The origin of patients' fears requires more attention in terms of
      treating endodontic-related fear and anxiety. More detailed research into the
      effects of demographics, causative factors and ethnicity on pathways of fear in
      dentistry is required to help dentists better manage patients in a multicultural
      society.

PMID- 25066389
TI  - Therapeutic potential and pharmacological activities of Atractylodes lancea
      (Thunb.) DC.
AB  - The rhizome of Atractylodes lancea (A. lancea) (Thunb.) DC. (AL) is extensively
      used in Chinese, Thai, and Japanese traditional medicines as crude
      extracts/decoctions or a component in various herbal formulations. Various
      pharmacological activities of AL and its major constituents have been
      demonstrated in vitro, ex vivo, and in animal models. Results from the toxicity
      studies in animal models suggest safety profile of AL and its active
      constituents. Despite extensive use with positive impression in many diseases,
      there has not been a clinical study that can conclusively support its efficacy
      and safety profile in human. This review comprehensively summarizes current
      information on the pharmacological activities of AL and their active constituents
      including anticancer, anti-inflammatory, antimicrobial and antipyretic
      activities, as well as activities on central nervous, cardiovascular, and
      gastrointestinal systems. 

PMID- 25066390
TI  - Depth of anaesthesia monitors and the latest algorithms.
AB  - This paper reviews the existing depth of anaesthesia (DoA) monitors and their
      algorithms and also proposes to improve their performance from four aspects. An
      ideal DoA monitor should be able to suggest a personalised drug dosage, to
      predict and provide early warnings when dosages are inappropriate, to be portable
      and highly cost-effective. The limitations of the existing DoA monitors commonly
      include unsatisfied data filtering techniques, time delay for the monitoring
      responses, and inflexible and low noise immunity problems. The latest research
      results show that their performance can be improved using up-to-date computing
      technology and neurophysiology. The findings in Chinese market review show that
      neither the imported nor the Chinese domestic DoA monitors are widely utilised at
      hospitals, but the demand for DoA monitors is very high. Clearly there is a high
      demand which encourages the development of a better DoA monitor and its mass
      production in China.

PMID- 25066391
TI  - Effect of diminazene aceturate, levamisole and vitamin C combination therapy in
      rats experimentally infected with Trypanosoma brucei brucei.
AB  - OBJECTIVE: To investigate the effect of diminazene aceturate (DA) alone or in
      combination with either levamisole and/or Vitamin C in albino rats experimentally
      infected with Trypanosoma brucei brucei. METHODS: Thirty adult male albino rats,
      randomly assigned into 6 groups (A-F) of 5 rats each were used. They were either
      infected with 1*10(6) trypanosomes intraperitoneally (groups A-E) or uninfected
      (group F). The different groups were treated respectively as follows: group A
      with 3.5 mg/kg DA; group B-3.5 mg/kg DA and 7.5 mg/kg levamisole; group C-3.5
      mg/kg DA and 100 mg/kg vitamin C; and group D-3.5 mg/kg DA and 7.5 mg/kg
      levamisole and 100 mg/kg vitamin C. Group E was left untreated. Parameters
      assessed include: rectal temperature, body weight changes, packed cell volume
      (PCV), Haemoglobin concentration (Hb), total leucocyte count (TLC) differential
      leucocyte count (DLC), parasitaemia, clinical signs and survivability. RESULTS:
      Average pre-patent period of 5 days was recorded. Parasites in the blood were
      cleared in all treated groups (A-D) within 48 hours post treatment (PT).
      Untreated rats in group E died between 25 and 32 days post infection (PI).
      Relapse was not recorded in all the treated groups (A-D). The initial reduction
      in PCV, Hb, TLC and increases in rectal temperature following infection were
      reversed by the treatments. The rats that received drug combinations (groups B, C
      and D) showed faster and higher recovery rates than the uninfected control and
      group A. CONCLUSIONS: Levamisole and/or Vitamin C combination with DA were more
      effective in the treatment of rats infected with Trypanosoma brucei brucei.

PMID- 25066392
TI  - Molecular phylogeny of trematodes in Family Heterophyidae based on mitochondrial
      cytochrome c oxidase subunit I (mCOI).
AB  - OBJECTIVE: To analyze a phylogenetic tree for understanding the molecular
      systematic of trematode in Family Heterophyidae, which are highly distributed in
      Thailand. METHODS: Based on thirteen sequences of mitochondrial cytochrome c
      oxidase subunit I (mCOI) gene from six genera of heterophyid trematodes, viz.
      Haplorchis, Stellantchasmus, Centrocestus, Metagonimus, Pygidopsis, and
      Haplorchoides were aligned automatically using the Clustal * 2.0 program. A
      phylogenetic tree was constructed by maximum likeinghood (ML) and neighbor
      joining (NJ) methods, with 1 000 bootstrap using the 5.0 program. RESULTS: The
      phylogenetic relationship from both methods was similar and separated into three
      groups consisting of Haplorchoides pumilio group, Haplorchoides taichui group and
      another heterophyid genera. CONCLUSIONS: The sequence data of mtCOI can be used
      to investigate the phylogenetic relationships of trematodes at the genus level.
      Each clade of different genera of heterophyid trematodes can be separated into
      sister groups that correlated with the morphological characteristic, kind of
      secondary intermediate host and geographic distribution.

PMID- 25066393
TI  - TIRAP rs8177374 gene polymorphism increased the risk of pulmonary tuberculosis in
      Zahedan, southeast Iran.
AB  - OBJECTIVE: To evaluate the possible association between Toll-interleukin 1
      receptor (TIR) domain containing adaptor protein (TIRAP; also known as MAL)
      rs1893352 and rs8177374 (S180L) gene polymorphisms and pulmonary tuberculosis
      (PTB) in a sample of Iranian population. METHODS: This case-control study was
      performed on 174 PTB and 177 healthy subjects. Tetra amplification refractory
      mutation system-polymerase chain reaction (T-ARMS-PCR) was used to detect the
      polymorphisms. RESULTS: Our finding showed that neither the overall Chi-square
      comparison of PTB and control subjects nor the logistic regression analysis
      indicated any association between rs1893352 polymorphism and PTB. Regarding
      rs8177374 polymorphism, the CT genotype as well as CT+TT increased the risk of
      PTB in comparison with CC genotype (OR=4.73, 95% CI=2.65-8.45, P<0.0001 and
      OR=6.47, 95% CI=3.68-11.38, P<0.0001, respectively). The rs8177374 T allele
      increased the risk of PTB in comparison with C allele (OR=4.21, 95% CI=2.43-7.26,
      P<0.0001). CONCLUSIONS: Our finding indicates that TIRAP rs8177374 polymorphism
      is associated with PTB in a sample of Iranian population.

PMID- 25066394
TI  - Synergistic effects of ethnomedicinal plants of Apocynaceae family and
      antibiotics against clinical isolates of Acinetobacter baumannii.
AB  - OBJECTIVE: To investigate the efficacy of 17 ethnomedicinal plants belonging to
      Apocynaceae family used in combination with 16 conventional antibiotics against
      non-multidrug resistant-, multidrug resistant (MDR)-, and extensive drug
      resistant (XDR) Acinetobacter baumannii (A. baumannii). METHODS: Antibacterial
      activity and resistance modifying ability of 272 combinations were determined by
      growth inhibition assays and further confirmed by time-kill assay. RESULTS: Among
      the combinations of the antibiotics with Apocynaceae ethanol extracts on this
      pathogen, 15 (5%) had synergistic effects, 23 (8%) had partial synergistic
      effects and 234 (86%) had no effects. Synergistic activity was observed mostly
      when the Apocynaceae extracts were combined with rifampicin or cefazolin.
      Interestingly, 10 out of 17 combinations between the extracts and rifampicin
      displayed synergistic or partial synergistic behaviors. Holarrhena
      antidysenterica extract was additionally tested to restore rifampicin activity
      against clinical isolates of MDR and XDR A. baumannii. With respect to total or
      partial synergy, 70% was XDR A. baumannii isolates and 66% was MDR A. baumannii
      isolates. CONCLUSIONS: Holarrhena antidysenterica extract clearly demonstrated
      the ability to restore rifampicin activity against both A. baumannii ATCC19606
      and clinically isolated A. baumannii. Additional studies examining its active
      principles as well as mechanisms of actions such as the effects on efflux pumps
      and outer membrane permeability alterations are recommended.

PMID- 25066395
TI  - Determinants of quinolone resistance in Escherichia coli causing community
      acquired urinary tract infection in Bejaia, Algeria.
AB  - OBJECTIVE: To investigate the mechanisms of quinolone resistance and the
      association with other resistance markers among Esherichia coli (E. coli) strains
      isolated from outpatient with urinary tract infection in north of Algeria.
      METHODS: A total of 30 nalidixic acid-resistant E. coli isolates from outpatient
      with urinary tract infections from January 2010 to April 2011 in north of Algeria
      (Bejaia) were studied. Antimicrobial susceptibility was determined by disc
      diffusion assay, minimal inhibitory concentrations (MIC) of quinolone were
      determined by microdilution. Mutations in the Quinolone Resistance-Determining
      Region (QRDR) of gyrA and parC genes and screening for qnr (A, B and S) and bla
      genes were done by PCR and DNA sequencing. RESULTS: Most of the E. coli isolates
      (56.66%) were shown to carry mutations in gyrA and parC (gyrA: Ser83Leu +
      Asp87Asn and parC:Ser80Ile). While, 16.66% had only an alteration in gyrA:
      Ser83Leu. One isolate produced qnrB-like and two qnrS-like. Four isolates were
      CTX-M-15 producers associated with TEM-1 producing in one case. Co-expression of
      blaCTX-M-15 and qnrB was determined in one E. coli isolate. CONCLUSIONS: Our
      findings suggested the community emergence of gyrA and parC alterations and Qnr
      determinants that contributed to the development and spread of fluoroquinolone
      resistance in Algerian E. coli isolates.

PMID- 25066396
TI  - Inhibited effects of veliparib combined doxorubicin for BEL-7404 proliferation of
      human liver cancer cell line.
AB  - OBJECTIVE: To explore inhibition effects of veliparib as PARP inhibitor combined
      doxorubicin for BEL-7404 proliferation of human liver cancer cell line. METHODS:
      BEL-7404 was taken as the object of study and conventional culture was performed.
      It was treated by doxorubicin and (or) veliparib after 24 h. Cell proliferation
      rate was detected by four methyl thiazolyl tetrazolium (MTT) assay, cell
      apoptosis was measured with annexin V-FITC/PI double staining method by flow
      cytometry, DNA damage degree evaluation by single cell gel electrophoresis assay,
      and cytosolic C levels of the mitochondrial and cytosol by polyacrylamide gel
      electrophoresis (Western blotting). RESULTS: Cell proliferation rate of
      doxorubicin combined veliparib group was lower than that of the control group and
      doxorubicin alone treated group significantly (P<0.01), the apoptosis rate was
      significantly higher than that of the control group and doxorubicin alone treated
      group (P<0.05). At the same time, DNA damage level of doxorubicin combined with
      veliparib group was significantly higher than doxorubicin alone treatment group
      and the control group (P<0.01), and cytochrome C in the cytosol was significantly
      higher than that of control group and doxorubicin alone treated group (P<0.01).
      CONCLUSIONS: Veliparib, PARP inhibitor could inhibit PARP activity, block tumor
      cell DNA repair, and have significant sensitizing effect for hepatocellular
      carcinoma cell line BEL-7404 treated with doxorubicin. This might provide a new
      target for clinical treatment of hepatic carcinoma.

PMID- 25066398
TI  - Effect of FK506 nanospheres on regeneration of allogeneic nerve after transplant.
AB  - OBJECTIVE: To discuss effect of FK506 nanospheres used at different time on the
      regeneration of allogeneic nerve after transplant. METHODS: Single emulsion
      solvent evaporation method (O/W) was adopted to prepare the FK506 nanospheres and
      the tibial nerve of rats after allogeneic transplantation. FK506 nanospheres were
      used in group A after operation immediately, in group B in 24 h after operation,
      and in group C in 3 d after operation while FK506 nanospheres were not used in
      group D; in the 4th, 8th and 12th week after operation respectively, general
      observation of transplanted nerves, histological examination, image analysis of
      myelinated fibers, wet-weight determination of musculi triceps surae,
      retrogradely labeling of neurons by the fluorescein and electrophysiological
      comparison of bilateral tibial nerve were carried out. RESULTS: FK506 nanospheres
      can be degraded and absorbed quickly. The neural regenerations in group A and B
      were similar, which were both much better than those in group C and D. The
      difference was statistically significant and so was the difference between group
      C and D. CONCLUSIONS: Drug release rate of FK506 nanospheres is accordant with
      the regeneration law of damaged nerves and the local application can promote the
      regenerations of nerves. The effect would be better if the drug is used in
      earlier period (within 24 h).

PMID- 25066397
TI  - Expression heterogeneity research of ITGB3 and BCL-2 in lung adenocarcinoma
      tissue and adenocarcinoma cell line.
AB  - OBJECTIVE: To analyze expression heterogeneity of Integrin beta 3 (ITGB3) and B
      cell lymphoma 2 (BCL-2) in lung adenocarcinoma tissue and adenocarcinoma cell
      line and further provide theoretical direction for molecular biological research
      of lung adenocarcinoma. METHODS: Tissue microarray was used to observe relation
      among expression, heterogeneitpy and clinical characteristics of ITGB3 and BCL-2
      in lung cancer. RESULTS: ITGB3 and BCL-2 increased significantly in A549 cells in
      CAFs group withbeta-actin as control; the expression level of BCL-2 also
      increased in ITGB3 transfected cells with GFP plasmid transfected A549 cells as
      control; immunohistochemistry staining showed that positive rates of ITGB3, ITGB1
      and BCL-2 in normal lung tissues were 0, the positive rates in lung
      adenocarcinoma were 7.04%, 84.51% and 4.23%, respectively; in the results of
      immunohistochemistry staining, the expression of Girdin protein in lung
      adenocarcinoma was homogeneous, however protein expression of ITGB3, ITGB1 and
      BCL-2 showed different patterns in the same location with significant
      heterogeneity; majority of ITGB3, ITGB1 or BCL-2 positive tissue showed
      heterogeneity that expression in trailing edge was higher than that of trailing
      edge in lung adenocarcinoma tissue, the patients with BCL-2 heterogeneity showed
      higher lymph node metastasis ratio and lower clinical stage (P<0.05); and the
      expression of ITGB3 and the clinical characteristics of patients were not
      significant related (P>0.05). CONCLUSIONS: Expression of ITGB3 and BCL-2 in lung
      adenocarcinoma and adenocarcinoma cell line showed heterogeneity that expression
      in trailing edge was higher than that of trailing edge, which may play an
      important role in promoting tumor lymph node metastasis and vascular invasion,
      and provides a new research direction for exploration of lung adenocarcinoma
      metastasis mechanism.

PMID- 25066399
TI  - Meta analysis of XRCC3 Thr241Met polymorphism and lung cancer susceptibility of
      populations in East Asia.
AB  - OBJECTIVE: To assess the relation between XRCC3 Thr241Met polymorphism and lung
      cancer susceptibility of populations in East Asia. METHODS: Related studies of
      XRCC3 Thr241Met polymorphism and lung cancer susceptibility of populations in
      East Asia were collected through searching the Pubmed, Embase Library, SPRINGER,
      CNKI and CSSCI. RESULTS: According to the entry criteria, there were 8 case
      control studies in the assessing system and there were 6 321 study cases,
      including 3 215 patients with lung cancer and 3 106 cases without cancers. Meta
      analysis results showed the combined OR value of the ratio of genotype
      Thr/Met+Met/Met and Thr/Thr was 1.03 (95%CI: 0.89-1.20) (P>0.05). CONCLUSIONS:
      XRCC3 Thr241Met polymorphism may not related to lung cancer susceptibility of
      populations in East Asia. Allele 241Met did not increase the risk of lung cancer.

PMID- 25066401
TI  - Effect of acupuncture on inflammatory cytokines expression of spastic cerebral
      palsy rats.
AB  - OBJECTIVE: To To investigate the effect of acupuncture on the tumor necrosis
      factor-alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP), nitric
      oxide synthase (NOS) content and muscular tension of spasticity cerebral palsy
      rat model. METHODS: The rats with spastic cerebral palsy were randomly divided
      into the control group, model group and acupuncture group. After successful
      modeling, the muscular tension and the content of TNF-alpha, IL-6, CRP, NOS were
      measured. RESULTS: The serum TNF-alpha, IL-6, CRP, NOS content were significantly
      decreased in the acupuncture group (P<0.05). The low and high shear viscosity of
      whole blood of the acupuncture group were significantly lower than the control
      group and the model group (P<0.05). The erythrocyte electrophoresis indexes in
      the acupuncture group were significantly lower than that in the model group and
      the control group (P<0.05). Acupuncture significantly reduced the muscular
      tension of spastic cerebral palsy rat and increased the active extent in the
      paralytic extremity (P<0.05), but it could not be restored to normal level.
      Compared with the control group, the difference had significant (P<0.05).
      CONCLUSIONS: Acupuncture treatment can inhibit the release of inflammatory cells
      after brain injury, then reduce immune injury, relieve muscle spasms and reduce
      muscular tension.

PMID- 25066400
TI  - Effect of WNT5A on epithelial-mesenchymal transition and its correlation with
      tumor invasion and metastasis in nasopharyngeal carcinoma.
AB  - OBJECTIVE: To investigate the correlation between nasopharyngeal carcinoma cell
      WNT5A and epithelial-mesenchymal transition (emt)/metastasis, and investigate its
      possible mechanisms. METHODS: RT-PCR and gene transfection were used to detect
      the expression of nasopharyngeal carcinoma cell strains WNT5A and EMT related
      factor 5-8F. Transient transfection of NPC cell line 5-8F was determined by
      liposome of plasmid with WNT5A gene. The differential expressions of WNT5A and
      EMT-related factors in cells before and after transfection were detected by RT
      PCR. Cell scratch assay and Transwell assay were used to detect the motility
      abilities of cells before and after 5-8F transfection. RESULTS: The expressions
      of WNT5A and EMT related factors matrix metalloproteinase-2 of the WNT5A
      transferred group in the nasopharyngeal carcinoma cell line 5-8F were higher than
      the blank control group and the empty vector transferred group, and the transfer
      ability of the WNT5A transferred group was higher than that in the blank control
      group and the empty vector transferred group, while the expressions of EMT
      related factors E-cadherin were lower than that in the blank control group and
      the empty vector transferred group, and the transfer ability of the WNT5A
      transferred group was higher than that in the blank control group and the empty
      vector transferred group. CONCLUSIONS: In nasopharyngeal carcinoma cells, WNT5A
      can regulate the epithelial-mesenchymal transition and affect the ability of
      tumor invasion and metastasis of nasopharyngeal carcinoma.

PMID- 25066402
TI  - Protective effect of topiramate on hypoxic-ischemic brain injury in neonatal rat.
AB  - OBJECTIVE: To explore protective effect of topiramate (TPM) on hypoxic-ischemic
      brain injury. METHODS: A total of 360 neonatal rats were selected then randomly
      divided into sham operation group, ischemia and hypoxia group, conventional
      treatment group and degradation therapy group (n=90). After surgical treatment,
      sham and ischemic hypoxia group were treat with normal saline; conventional
      treatment group was received TPM solution 100 mg/kg, 2 times/d; degradation
      therapy group received TPM solution 150 mg/kg, 2 times/d, per 3 d treatment each
      dosage was reduced 50 mg/kg, the lowest reduced to 50 mg/kg. Four groups received
      continuous treatment for 10 d. After treatment for 1 d, 4 d, 7 d, 10 d the
      cerebral edema, neuron-specific enolase (NSE) and gamma-aminobutyric acid (GABA)
      levels and cognitive abilities of four groups were observed. RESULTS: After 1 d,
      4 d of treatment, the brain water content and NSE levels in ischemia and hypoxia
      group, the conventional treatment group and the degradation therapy group were
      significantly higher than that in sham group (P<0.05), the brain water content
      and NSE levels of the conventional treatment group and the degradation therapy
      group were significantly lower than that in the ischemic hypoxia group (P<0.05).
      GABA levels and learning ability of the ischemia and hypoxia group, the
      conventional treatment group and degradation therapy group were significantly
      lower than the sham group (P<0.05), the GABA levels and learning ability of the
      conventional treatment group and degradation therapy group were significantly
      higher than the ischemia and hypoxia group (P<0.05). After 7 d, 10 d of
      treatment, the brain water content and NSE levels in the sham operation group,
      the conventional treatment group and degradation therapy group were significantly
      lower than the ischemia and hypoxia group (P<0.05), while the GABA levels and
      learning ability of these three groups were significantly higher than that in the
      ischemia and hypoxia group (P<0.05), the GABA levels in the conventional
      treatment group were significantly higher than degradation therapy group
      (P<0.05); After 10 d of treatment, the GABA levels of the conventional treatment
      group were significantly higher than the sham group, the learning ability of the
      degradation therapy group and sham operation group were significantly higher than
      the conventional treatment group (P<0.05). CONCLUSIONS: The correct amount of
      short-term TPM has protective effect on hypoxic-ischemic brain injury, but long
      term or excessive use may cause new damage to the brain and reduce the cognitive
      ability.

PMID- 25066403
TI  - Prevention effect of medical self-crosslinking sodium hyaluronate gel on epidural
      scar adhesion after laminectomy.
AB  - OBJECTIVE: To analyze the effect and medical self-crosslinking sodium hyaluronate
      gel on epidural scar adhesion after laminectomy. METHODS: A total of 24 New
      Zealand L5 laminectomy rabbits were randomly divided into four groups, group A as
      the control group without any treatment; group B covered by sodium hyaluronate
      gel; group C and group D covered by 0.5 and 1.0 mL medical self-crosslinking
      sodium hyaluronate gel. All rabbits were scored at various time points after 2,
      4, 6, 8, 12 weeks, then the formation of scar was observed. RESULTS: In Groups B,
      C, D loose scar tissue occurred after 2 weeks of the operation, scar tissues were
      significantly less than that in group A, with mild inflammatory reaction. After 8
      weeks, the scar tissues of group B were significantly more than that of groups C,
      D. After two weeks, group B, C were back to the preoperative level; After 4
      weeks, group D was back to the preoperative level; After four weeks, the CSEP of
      group A was increased significantly, which was significantly higher than that in
      groups B, C, D. The motor function score of group A, group B and group C were the
      same as preoperative, but that in group D it was decreased significantly, and
      then it gradually recovered. After 4 weeks it kept a stable level. The motor
      function score of group A was decreased gradually after the operation, which kept
      a stable level after 4 weeks, the motor function score was significantly lower
      than that in groups B, C, D. CONCLUSIONS: Determination of somatosensory evoked
      potentials is sensitive indicator of spinal cord injury; Application of medical
      self-crosslinking sodium hyaluronate gel is effective on epidural scar adhesion
      after laminectomy.

PMID- 25066404
TI  - Positive response to cardiac resynchronization therapy reduces arrhythmic events
      after elective generator change in patients with primary prevention CRT-D.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) and implantable
      cardioverter-defibrillators (ICD) are effective therapies for heart failure (HF)
      patients with cardiac dyssynchrony. Patients receiving primary prevention CRT
      defibrillator that positively remodel might no longer qualify for ICD indication
      due to CRT-induced left ventricular ejection fraction (LVEF) improvement. We
      aimed to evaluate the outcome of CRT-D patients at the time of device replacement
      (DR). METHODS AND RESULTS: Patients undergoing primary prevention CRT-D DR were
      prospectively included from November 2007 to March 2011 in 2 centers. CRT
      response was as defined as >=1 NYHA class improvement and an increase in LVEF
      >=10%. Before DR, all patients underwent echocardiography and device
      interrogation. Patients without theoretical ongoing ICD indication (TOII) at DR
      were defined as those with LVEF >=40% without appropriate ICD therapy
      (appropriate therapy) during the first ICD service-life. A total of 107
      consecutive patients were enrolled. Sixty-one patients (57%) were considered CRT
      responders after the index procedure. At the time of DR (56.4 +/- 14.4 months
      from initial implant), 87% of CRT responders were free of appropriate therapy,
      compared with 70% of CRT nonresponders (P = 0.02). Thirty-nine patients (37%) did
      not meet the criteria for TOII. During follow-up (mean 26.4 +/- 14.4 months after
      DR), 37 patients (95%) without TOII were free of appropriate therapy versus 49 of
      68 patients (72%) with ongoing TOII (P = 0.007). By multivariable analysis, the
      only independent predictor of appropriate therapy after DR was TOII (hazard ratio
      = 6.43; P = 0.01). CONCLUSION: Absence of theoretical ICD indication occurs in
      more than one-third of CRT-D patients undergoing DR. In addition, appropriate
      therapy rate is relatively low (2.2% per year) in this subgroup of patients.

PMID- 25066405
TI  - Basal serum cortisol concentration as a screening test for hypoadrenocorticism in
      dogs.
AB  - BACKGROUND: Measurement of basal serum or plasma cortisol concentration is used
      as a screening test for hypoadrenocorticism in dogs, but is not well
      characterized. OBJECTIVES: To evaluate the sensitivity and specificity of basal
      serum cortisol to detect hypoadrenocorticism in a population of dogs with a
      clinical suspicion of hypoadrenocorticism. ANIMALS: Four hundred and fifty dogs
      with nonadrenal gland illness and 14 dogs with naturally occurring
      hypoadrenocorticism were included. METHODS: Retrospective case-control study. The
      records of all dogs having had an ACTH stimulation test performed between January
      2005 and September 2011 at the University of Bristol were reviewed. Dogs were
      included if the test was performed as a screening for hypoadrenocorticism. The
      sensitivity and specificity of basal serum cortisol concentration to detect dogs
      with hypoadrenocorticism were calculated using 2 cut-offs and compared to the
      gold standard ACTH stimulation test. RESULTS: Using a cut-off of <=2 MUg/dL (<=55
      nmol/L), the sensitivity and specificity of basal cortisol to detect
      hypoadrenocorticism were 100% and 63.3%, respectively, whereas for a cut-off of
      <=1 MUg/dL (<=28 nmol/L), the sensitivity and specificity were 85.7% and 91.8%,
      respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of basal serum
      cortisol is useful as a screening test for hypoadrenocorticism in dogs using a
      cut-off of <=2 MUg/dL (<=55 nmol/L), and the disease is unlikely with a basal
      serum cortisol >2 MUg/dL (>55 nmol/L). A basal serum cortisol <=2 MUg/dL (<=55
      nmol/L) cannot be used to diagnose hypoadrenocorticism, and an ACTH stimulation
      test should be performed in these cases.

PMID- 25066406
TI  - An Exploratory Case-Control Study on the Impact of IL-1 Gene Polymorphisms on
      Early Implant Failure.
AB  - BACKGROUND: The association between IL-1 gene polymorphisms and peri-implantitis
      has been well documented. However, data on the association with early implant
      failure are scarce. PURPOSE: The objective of this case-control study was to
      explore the impact of IL-1A (-889), IL-1B (-511), and IL-1B (+3,954) gene
      polymorphisms on early implant failure in Caucasians. MATERIALS AND METHODS:
      Between September 2004 and August 2007, 461 patients were treated with dental
      implants at the University Hospital in Ghent, Belgium. Fourteen subjects of this
      patient group who had experienced one or more early implant failures (within 6
      months from implant installation) were recruited as "cases." Fourteen "controls,"
      matched in terms of age, gender, and smoking habits, with only surviving
      implants, were selected from the same patient group. Allele and genotype analysis
      was performed on the basis of a blood sample by Sanger sequencing of polymerase
      chain reaction products containing the IL-1A (-889), IL-1B (-511), and IL-1B
      (+3,954) gene polymorphisms. RESULTS: A significant impact of the IL-1A (-889) T
      allele (p = .039) and the IL-1B (+3,954) T allele (p = .003) on early implant
      failure was demonstrated (odds ratios = 3.9 and 15.0, respectively). In addition,
      the genotypic distribution differed significantly between cases and controls for
      IL-1B (+3,954) (p = .015). CONCLUSIONS: The IL-1B (+3,954) gene polymorphism
      seems to affect osseointegration. Additional case-control studies in larger
      patient groups are needed to confirm this observation.

PMID- 25066407
TI  - Multidisciplinary care improves clinical outcome and reduces medical costs for
      pre-end-stage renal disease in Taiwan.
AB  - AIM: Multidisciplinary care (MDC) for patients with chronic kidney disease (CKD)
      may help to optimize disease care and improve clinical outcomes. Our study aimed
      to evaluate the effectiveness of pre-end-stage renal disease (ESRD) patients
      under MDC and usual care in Taiwan. METHOD: In this 3-year retrospective
      observational study, we recruited 822 ESRD subjects, aged 18 years and older,
      initiating maintenance dialysis more than 3 months from five cooperating
      hospitals. The MDC (n = 391) group was cared for by a nephrologists-based team
      and the usual care group (n = 431) was cared for by sub-specialists or
      nephrologists alone more than 90 days before dialysis initiation. Patient
      characteristics, dialysis modality, hospital utilization, hospitalization at
      dialysis initiation, mortality and medical cost were evaluated. Medical costs
      were further divided into in-hospital, emergency services and outpatient visits.
      RESULTS: The MDC group had a better prevalence in peritoneal dialysis (PD)
      selection, less temporary catheter use, a lower hospitalization rate at dialysis
      initiation and 15% reduction in the risk of hospitalization (P < 0.05). After
      adjusting for gender, age and Charlson Comorbidity Index score, there were lower
      in-hospital and higher outpatient costs in the MDC group during 3 months before
      dialysis initiation (P < 0.05). In contrast, medical costs (NT$ 146,038 vs
      79,022) and hospitalization days (22.4 vs 15.5 days) at dialysis initiation were
      higher in the usual care group. Estimated medical costs during 3 months before
      dialysis till dialysis initiation, the MDC group yielded a reduction of NT$
      59,251 for each patient (P < 0.001). Patient mortality was not significantly
      different. CONCLUSION: Multidisciplinary care intervention for pre-ESRD patients
      could not only significantly improve the quality of disease care and clinical
      outcome, but also reduce medical costs.

PMID- 25066409
TI  - Limited validity of diagnosis codes in Medicare claims for identifying cancer
      metastases and inferring stage.
AB  - PURPOSE: Researchers are using diagnosis codes from health claims to identify
      metastatic disease in cancer patients. The validity of this approach has not been
      established. METHODS: We used the linked 2005-2007 Surveillance, Epidemiology and
      End Results (SEER)-Medicare data to assess the validity of metastasis codes at
      diagnosis from claims compared with stage reported by SEER cancer registries. The
      cohort included 80,052 incident breast, lung, and colorectal cancer patients aged
      65 years and older. Using gold-standard SEER data, we evaluated sensitivity,
      specificity, positive predictive value, and negative predictive value of claims
      based stage, survival by stage classification, and patient factors associated
      with stage misclassification using multivariable regression. RESULTS: For
      patients with a registry report of distant metastatic cancer, the sensitivity,
      specificity, and positive predictive value of claims never simultaneously
      exceeded 80% for any cancer: lung (42.7%, 94.8%, and 88.1%), breast (51.0%,
      98.3%, and 65.8%), and colorectal (72.8%, 93.8%, and 68.5%). Misclassification of
      stage from Medicare claims was significantly associated with inaccurate estimates
      of stage-specific survival (P < .001). In adjusted analysis, patients who were
      older, black, or living in low-income areas were more likely to have their stage
      misclassified in claims. CONCLUSIONS: Diagnosis codes in Medicare claims have
      limited validity for inferring cancer stage and metastatic disease.

PMID- 25066410
TI  - Mesenteric masses: approach to differential diagnosis at MRI with histopathologic
      correlation.
AB  - Magnetic resonance imaging (MRI) is an outstanding tool for the identification
      and characterization of mesenteric masses. Mesenteric masses may be solid or
      cystic. Most solid mesenteric masses are neoplastic, with sclerosing mesenteritis
      a notable exception. Entirely cystic mesenteric masses are typically benign. The
      excellent soft-tissue contrast afforded by MRI aids in narrowing the differential
      diagnosis of mesenteric masses. Accurately characterizing both solid and cystic
      mesenteric masses is important, as management ranges from active surveillance to
      medical management to surgical resection, depending on the tissue composition of
      the mass. An MRI-based approach to the differential diagnosis of mesenteric
      masses is presented.

PMID- 25066408
TI  - Four-dimensional MRI of renal function in the developing mouse.
AB  - The major roles of filtration, metabolism and high blood flow make the kidney
      highly vulnerable to drug-induced toxicity and other renal injuries. A method to
      follow kidney function is essential for the early screening of toxicity and
      malformations. In this study, we acquired high spatiotemporal resolution (four
      dimensional) datasets of normal mice to follow changes in kidney structure and
      function during development. The data were acquired with dynamic contrast
      enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to
      obtain a full three-dimensional image (isotropic resolution, 125 microns) every
      7.7 s over a 50-min scan. This time course permitted the demonstration of both
      contrast enhancement and clearance. Functional changes were measured over a 17
      week course (at 3, 5, 7, 9, 13 and 17 weeks). The time dimension of the MRI
      dataset was processed to produce unique image contrasts to segment the four
      regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM),
      inner stripe (IS) of the OM and inner medulla (IM). Local volumes, time-to-peak
      (TTP) values and decay constants (DC) were measured in each renal region. These
      metrics increased significantly with age, with the exception of DC values in the
      IS and OS. These data will serve as a foundation for studies of normal renal
      physiology and future studies of renal diseases that require early detection and
      intervention.

PMID- 25066411
TI  - Near-infrared-emitting two-dimensional codes based on lattice-strained
      core/(doped) shell quantum dots with long fluorescence lifetime.
AB  - Lattice-strained CdTe/CdS:Cu quantum dots (QDs) with a widely tunable near
      infrared (NIR) fluorescence emission spectrum (700-910 nm) and long lifetime (up
      to 1 MUs) are synthesized. Based on the multiemission and multi-lifetime of the
      well-defined QDs, NIR-emitting two-dimensional (2D) codes are achieved by
      embedding as-prepared QDs into agarose beads. This provides a new strategy for
      fluorescent 2D codes. 

PMID- 25066412
TI  - Continuous subcutaneous insulin infusion preserves axonal function in type 1
      diabetes mellitus.
AB  - BACKGROUND: Diabetic peripheral neuropathy is a common and debilitating
      complication of diabetes mellitus. Although strict glycaemic control may reduce
      the risk of developing diabetic peripheral neuropathy, the neurological benefits
      of different insulin regimens remain relatively unknown. METHODS: In the present
      study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical
      neurological assessment. Subsequently, 41 non-neuropathic patients, 24 of whom
      were receiving multiple daily insulin injections (MDII) and 17 receiving
      continuous subcutaneous insulin infusion (CSII), underwent nerve excitability
      testing, a technique that assesses axonal ion channel function and membrane
      potential in human nerves. Treatment groups were matched for glycaemic control,
      body mass index, disease duration and gender. Neurophysiological parameters were
      compared between treatment groups and those taken from age and sex-matched normal
      controls. RESULTS: Prominent differences in axonal function were noted between
      MDII-treated and CSII-treated patients. Specifically, MDII patients manifested
      prominent abnormalities when compared with normal controls in threshold
      electrotonus (TE) parameters including depolarizing TE(10-20ms), undershoot and
      hyperpolarizing TE (90-100 ms) (P < 0.05). Additionally, recovery cycle
      parameters superexcitability and subexcitability were also abnormal (P < 0.05).
      In contrast, axonal function in CSII-treated patients was within normal limits
      when compared with age-matched controls. The differences between the groups were
      noted in cross-sectional analysis and remained at longitudinal follow-up.
      CONCLUSIONS: Axonal function in type 1 diabetes is maintained within normal
      limits in patients treated with continuous subcutaneous insulin infusion and not
      with multiple daily insulin injections. This raises the possibility that CSII
      therapy may have neuroprotective potential in patients with type 1 diabetes.

PMID- 25066413
TI  - Minority mothers' healthcare beliefs, commonly used alternative healthcare
      practices, and potential complications for infants and children.
AB  - PURPOSE: Complementary and alternative healthcare practices have increased
      substantially in the United States especially with low-income ethnic minority
      mothers. These mothers often have provider mistrust, language barriers, differing
      health belief systems, and as a result are less likely to seek preventive health
      screening, access healthcare services, and use alternative remedies for their
      infants and children that are potentially harmful or lethal. Therefore, the
      purpose of this article is to examine healthcare beliefs, commonly used
      alternative healthcare practices, and their potential complications for infants
      and children. DATA SOURCES: A search of CINAHL and PubMed (1980-2012) was
      conducted using the following terms: alternative healthcare practice, mothers'
      health beliefs, cultural health beliefs, folk remedies, and infant health
      practices. CONCLUSION: Given the changing U.S. population and an increasing
      immigrant population, examining alternative healthcare practices mothers use for
      their infants and children is especially important for providers in addressing
      healthcare for this group. IMPLICATIONS FOR PRACTICE: The use of alternative
      healthcare practices is rarely discussed by parents with healthcare providers for
      fear of disapproval. When interviewing ethnic minority mothers and caregivers
      questions should include the use of alternative healthcare practices for infants
      and children and information regarding the potential dangers should be provided
      to them.

PMID- 25066414
TI  - Effect of inoculum source on the enrichment of microbial communities on two
      lignocellulosic bioenergy crops under thermophilic and high-solids conditions.
AB  - AIMS: Culturing compost-derived microbial communities on biofuel feedstocks under
      industrial conditions is a technique to enrich for organisms and
      lignocellulolytic enzymes for bioenergy feedstock deconstruction. In this study,
      microbial communities from green waste compost (GWC) and grape pomace compost
      (GPC) were cultured on switchgrass and eucalyptus to observe the impact of
      inoculation on feedstock decomposition and microbial community structure. METHODS
      AND RESULTS: Respiration was monitored as a measure of microbial activity, and
      16S ribosomal RNA gene sequencing was used to characterize microbial community
      structure. The enriched community structure and respiration were influenced by
      the choice of feedstock, compost type, and application of thermophilic, high
      solids conditions. However, the effect of compost source was significantly less
      than the effects of the other culture variables. CONCLUSIONS: Although there are
      subtle differences in potentially lignocellulolytic taxa between GPC- and GWC
      derived communities, these differences do not affect the decomposition rates for
      these communities on switchgrass or eucalyptus. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These results are useful for designing future experiments to discover
      lignocellulolytic micro-organisms from compost. They suggest that such work may
      be better served by deemphasizing screening of compost sources and instead
      focusing on how compost-derived communities adapt to the feedstocks and process
      conditions relevant to biofuel production.

PMID- 25066415
TI  - Atypical presentation of herpetic whitlow as dark brown vesicles in a
      hyperbilirubinemic patient.

PMID- 25066416
TI  - Childhood trauma and risky alcohol consumption: a study of Australian adults with
      low housing stability.
AB  - INTRODUCTION AND AIMS: This paper examined whether recall of childhood trauma was
      associated with adult alcohol consumption in a sample of Australians with low
      housing security. The secondary aim was to examine whether risky alcohol
      consumption predicted subsequent housing instability. Sociodemographic factors
      were examined as potential moderators of these associations. DESIGN AND METHODS:
      This paper utilised data collected through the Journeys Home Study, a
      longitudinal study of a representative sample of individuals who were homeless or
      at risk of homelessness. This paper focused on 1224 participants aged 18 years
      and over. Data on alcohol use, childhood trauma and sociodemographic
      characteristics were collected through interviews at baseline. Homeless status at
      6- to 12-month follow-up was assessed via interview. Logistic regression
      modelling was used to examine associations of alcohol consumption with childhood
      abuse, sociodemographic factors and changes in homelessness status. RESULTS: Self
      reported recall of childhood experiences of violence was more likely among
      current drinkers, risky or not, than among abstainers. Recall of childhood
      neglect was more common among abstainers than among risky drinkers. DISCUSSION
      AND CONCLUSIONS: The relationships between recall of childhood trauma and adult
      alcohol consumption are likely to be complex. Risky consumption may contribute to
      continuing homelessness among adults with unstable housing. [Correction added on
      29 December 2014, after first online publication: The Results, and Discussion and
      Conclusion sections in the abstract have been replaced.].

PMID- 25066417
TI  - Establishing tobacco origin from pollen identification: an approach to resolving
      the debate.
AB  - Previous research into pollen content of tobacco resulted in a debate. We address
      this debate and determine that pollen analysis may be able to assist with
      identifying geographical origin of tobacco. However, the value of any results
      should be assessed on a case-by-case regional basis until sufficient database
      information is available for an objective interpretation to be undertaken on a
      global basis. As a first step toward developing comparative data for South
      America, we analyzed a tobacco sample from Brazil in an effort to identify
      signature taxa from the state of Minas Gerais. We also assessed the role of honey
      additives to tobacco to assess this issue. Comparing the data to previously
      published data, we conclude that pollen signatures can distinguish broad
      geographic areas. We conclude that this forensic interpretation framework needs
      to be developed in context of the National Academy of Sciences recommendations
      for tightening methods in forensic science. 

PMID- 25066418
TI  - Validation of an enzyme immunoassay for the measurement of faecal glucocorticoid
      metabolites in Eurasian (Lynx lynx) and Iberian lynx (Lynx pardinus).
AB  - Stress hormone levels are important indicator of an animal's well-being, as
      stress has harmful effects on reproduction, growth and immune function. The
      development of enzyme immunoassays (EIA) to monitor faecal glucocorticoid
      metabolites (fGM) contributes a powerful tool to assess an animal's adrenal
      status non-invasively. We aimed to identify a suitable EIA for monitoring fGM by
      assessing the suitability of six different EIAs for detecting quantitative
      changes in fGM concentrations in response to an ACTH challenge test in Eurasian
      lynx. FGM were characterised in a male Eurasian lynx that received an injection
      of (3)H-cortisol. Using HPLC analyses radiolabeled metabolites were compared with
      immunoreactive metabolites. The second aim was to biologically validate the
      established EIA for monitoring adrenocortical activity of captive Iberian lynxes
      after a translocation to new enclosures in relation to behaviour. Additionally
      faecal samples of ten pregnant Iberian lynxes from the peripartal period were
      analysed. The ACTH challenge revealed an 11beta-hydroxyetiocholanolone EIA as the
      most sensitive assay to reflect acute fGM elevations in the Eurasian lynx. HPLC
      immunograms demonstrated that the 11beta-hydroxyetiocholanolone EIA measured
      significant amounts of immunoreactivities corresponding to radiolabeled
      metabolites with strong similarities across both lynx species. Additionally, HPLC
      and GC-MS analyses confirmed the presence of 11beta-hydroxyetiocholanolone in
      faeces of both, the Eurasian and the Iberian lynx. Longitudinal fGM profiles of
      Iberian lynx revealed increases in concentrations associated with management
      events. During the peripartal period, however, fGM concentrations were not
      significantly elevated. Our results show that the 11beta-hydroxyetiocholanolone
      EIA is a reliable tool to assess fGM in both lynx species. 

PMID- 25066419
TI  - Early CD8 T-cell memory precursors and terminal effectors exhibit equipotent in
      vivo degranulation.
AB  - Early after priming, effector CD8 T cells are distinguished into memory precursor
      and short-lived effector cell subsets (MPECs and SLECs). Here, we delineated a
      distinct in vivo heterogeneity in killer cell lectin-like receptor G1 (KLRG-1)
      expression, which was strongly associated with diverse MPEC and SLEC fates. These
      in vivo MPECs and SLECs expressed equivalent levels of cytotoxic molecules and
      effector cytokines. Using a unique in vivo degranulation assay, we found that the
      MPECs and SLECs similarly encountered infected target cells and elaborated
      equivalent levels of cytotoxicity in vivo. These data provide direct in vivo
      evidence that memory-fated cells pass through a robust effector phase.
      Additionally, the preferential localization of the MPECs in the lymph nodes,
      where a lesser degree of cytotoxicity was elaborated, suggests that the MPECs may
      be protected from excessive stimulation and terminal differentiation by virtue of
      their differential tissue localization. These data provide novel mechanistic
      insights into the linear decreasing potential model of memory differentiation.

PMID- 25066420
TI  - Reproductive immunology issue one: cellular and molecular biology.

PMID- 25066421
TI  - Tracking cytotoxic potential in vivo.

PMID- 25066423
TI  - Structural and functional analyses of human tryptophan 2,3-dioxygenase.
AB  - Tryptophan 2,3-dioxygenase (TDO), one of the two key enzymes in the kynurenine
      pathway, catalyzes the indole ring cleavage at the C2-C3 bond of L-tryptophan.
      This is a rate-limiting step in the regulation of tryptophan concentration in
      vivo, and is thus important in drug discovery for cancer and immune diseases.
      Here, we report the crystal structure of human TDO (hTDO) without the heme
      cofactor to 2.90 A resolution. The overall fold and the tertiary assembly of hTDO
      into a tetramer, as well as the active site architecture, are well conserved and
      similar to the structures of known orthologues. Kinetic and mutational studies
      confirmed that eight residues play critical roles in L-tryptophan oxidation.

PMID- 25066424
TI  - The quality of the interparental relationship does not moderate the etiology of
      child conduct problems.
AB  - BACKGROUND: Although there is a clear phenotypic relationship between the quality
      of the interparental or marital relationship and child conduct problems (CP), the
      etiology of this association is as yet unclear. One possibility is that this
      association takes the form of a genotype-environment interaction (G * E), whereby
      the quality of the interparental relationship acts to moderate the etiology of
      child CP. The current study sought to evaluate this possibility. METHOD: We
      examined multiple measures and informant reports of the quality of the
      interparental relationship in a sample of more than 700 child twin families from
      the Michigan State University Twin Registry (MSUTR). Analyses consisted of a
      series of latent G * E models. RESULTS: The 'no moderation' model provided the
      best fit to the data in nearly all cases, findings that collectively provide
      strong evidence against the possibility that the etiology of CP is moderated by
      the quality of the interparental relationship. CONCLUSIONS: Our findings suggest
      that, contrary to implicit (and sometimes explicit) assumptions in the field, it
      is not the case that every environmental risk (or protective) factor exacerbates
      (or suppresses) genetic influences on CP. Future research should seek to
      delineate the specific environmental experiences that do serve as etiologic
      moderators of CP, and to clarify how this G * E interplay might change over the
      course of development.

PMID- 25066425
TI  - Bipolar disorder: recent clinical trials and emerging therapies for depressive
      episodes and maintenance treatment.
AB  - Bipolar disorder (BD) is one of the world's ten most disabling conditions. More
      options are urgently needed for treating bipolar depressive episodes and for
      safer, more tolerable long-term maintenance treatment. We reviewed 30 recent
      clinical trials in depressive episodes (eight tested compounds) and 14 clinical
      trials in maintenance treatment (ten tested compounds). Positive results in Phase
      III trials, regulatory approval and/or new therapeutic indications were obtained
      with some of the developing drugs, particularly for depressive episodes. The
      current BD pipeline is encouraging with promising new compounds, acting on novel
      pharmacological targets and on specific aspects of bipolar depression. 

PMID- 25066426
TI  - Late gadolinium enhancement CMR in primary mitral regurgitation.
AB  - AIMS: The appropriate timing for surgery in severe asymptomatic primary mitral
      regurgitation (MR) remains controversial. It has been shown that late gadolinium
      enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify
      myocardial fibrosis, is associated with a worse outcome in various
      cardiomyopathies. We sought to investigate the prevalence and significance of
      delayed enhancement in primary MR. METHODS: We prospectively included 41 patients
      with at least moderate primary MR and without overt signs of left ventricular
      (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias
      or significant concomitant valvular disease were excluded. All patients were
      scheduled for transthoracic echocardiography and LGE CMR. RESULTS: A total of 39
      patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast
      uptake of the LV wall. LGE CMR showed an infarct pattern in three patients, a
      pattern of mid-wall fibrosis in seven patients and two patients had a combined
      pattern. Patients with delayed enhancement on CMR had significant higher LV
      diameters (LV end-systolic diameter 39 +/- 4 vs. 34 +/- 5 mm, P = 0.002; LV end
      diastolic diameter 57 +/- 5 vs. 50 +/- 5 mm, P = 0.001). There was a trend
      towards a higher indexed left atrial volume (55 +/- 21 vs. 44 +/- 13 mL/m2, P =
      0.06). By contrast, there was no significant association between myocardial
      contrast uptake and age, LV ejection fraction and MR severity. CONCLUSION: Left
      ventricular remodelling seems to be associated with the presence of delayed
      enhancement on CMR in primary MR. Further data are needed to determine whether
      LGE CMR can predict a less favourable outcome or could improve risk
      stratification in asymptomatic primary MR.

PMID- 25066422
TI  - Leukocyte driven-decidual angiogenesis in early pregnancy.
AB  - Successful pregnancy and long-term, post-natal maternal and offspring cardiac,
      vascular and metabolic health require key maternal cardiovascular adaptations
      over gestation. Within the pregnant decidualizing uterus, coordinated vascular,
      immunological and stromal cell changes occur. Considerable attention has been
      given to the roles of uterine natural killer (uNK) cells in initiating decidual
      spiral arterial remodeling, a process normally completed by mid-gestation in mice
      and in humans. However, leukocyte roles in much earlier, region specific,
      decidual vascular remodeling are now being defined. Interest in immune cell
      promoted vascular remodeling is driven by vascular aberrations that are reported
      in human gestational complications such as infertility, recurrent spontaneous
      abortion, preeclampsia (PE) and fetal growth restriction. Appropriate maternal
      cardiovascular responses during pregnancy protect mothers and their children from
      later cardiovascular disease risk elevation. One of the earliest uterine
      responses to pregnancy in species with hemochorial placentation is stromal cell
      decidualization, which creates unique niches for angiogenesis and leukocyte
      recruitment. In early decidua basalis, the aspect of the implantation site that
      will cradle the developing placenta and provide the major blood vessels to
      support mature placental functions, leukocytes are greatly enriched and display
      specialized properties. UNK cells, the most abundant leukocyte subset in early
      decidua basalis, have angiogenic abilities and are essential for normal early
      decidual angiogenesis. The regulation of uNK cells and their roles in determining
      maternal and progeny cardiovascular health over pregnancy and postpartum are
      discussed. 

PMID- 25066428
TI  - A technique for retrofitting a metal ceramic crown to an attachment-retained
      removable partial denture: a clinical report.
AB  - In dental applications, precision attachments have been used to retain removable
      partial dentures (RPDs) for several decades. Various types of extracoronal
      attachments are commonly used in combination with fixed partial dentures and RPDs
      to achieve retention and stability. Fracture of the framework, fracture of the
      roots or teeth, and irretrievable decrease of retention are common reasons for a
      failed attachment-retained RPD. Another complication of metal ceramic crowns with
      precision attachment is decementation of the crowns. When fixed components of the
      attachment-retained RPD fail, the traditional treatment approach requires
      remaking both the fixed and removable components of the attachment-retained RPD.
      This technique describes retrofitting of a metal ceramic crown to a resilient
      attachment-retained RPD. 

PMID- 25066427
TI  - The use of 3D planning in facial surgery: preliminary observations.
AB  - Three-dimensional (3D) planning is becoming a more commonly used tool in
      maxillofacial surgery. At first used only virtually, 3D planning now also enables
      the creation of useful intraoperative aids such as cutting guides, which decrease
      the operative difficulty. In our center, we have used 3D planning in various
      domains of facial surgery and have investigated the advantages of this technique.
      We have also addressed the difficulties associated with its use. 3D planning
      increases the accuracy of reconstructive surgery, decreases operating time,
      whilst maintaining excellent esthetic results. However, its use is restricted to
      osseous reconstruction at this stage and once planning has been undertaken, it
      cannot be reversed or altered intraoperatively. Despite the attractive nature of
      this new tool, its uses and practicalities must be further evaluated. In
      particular, cost-effectiveness, hospital stay, and patient perceived benefits
      must be assessed. 

PMID- 25066429
TI  - Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008
      through 2011.
AB  - We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin
      resistant Staphylococcus aureus collected from nationwide hospitals in Japan over
      a three-year period from January 2008 through May 2011. Antibiotic susceptibility
      was judged according to the criteria recommended by the Clinical Laboratory
      Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin,
      linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them
      were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA
      strains showed resistant to minocycline, meropenem, imipenem, clindamycin,
      ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7,
      89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced
      susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin
      intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin
      intermediate S. aureus (hVISA), and 55 (5.63%) of beta-lactam antibiotics-induced
      vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55
      BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR
      phenotypes. A new trend of vancomycin resistance found in this study was that
      VISA strains were still prevalent among the bacteremic specimens. The high rates
      of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of
      VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan.

PMID- 25066430
TI  - [Leuko-glycaemic index in ST elevation acute myocardial infarction, a simple and
      useful parameter in the predicting complications].

PMID- 25066431
TI  - The Role of Nicotine in the Corrosive Behavior of a Ti-6Al-4V Dental Implant.
AB  - BACKGROUND: Metals react chemically/electrochemically in electrolytic solutions,
      such as that present in the oral cavity, which leads to corrosion of metal dental
      implants. Corrosion can increase the failure rate of dental implants. PURPOSE:
      This study evaluated the corrosion behavior of nicotine on Ti-6Al-4V under
      physiological conditions. It was hypothesized that nicotine in artificial saliva
      would have an adverse effect on the corrosion of Ti-6Al-4V. METHODS: Ti-6Al-4V
      discs were electrochemically analyzed using a three-electrode electrochemical
      cell. The disks were immersed in an electrolytic artificial saliva with varying
      pH (3.0 and 6.5) and nicotine concentration (control, 1 mg/mL, 5 mg/mL, and 20
      mg/mL). Open circuit potential, cyclic polarization, and electrochemical
      impedance spectroscopy (EIS) tests were conducted. RESULTS: Electrochemical
      parameters indicated that the presence of nicotine significantly reduced (p <
      .05) the corrosion rate. For example, there was a decrease in corrosion current
      density from 2.94 * 10(-3)  MUA/cm(2) to 1.43 * 10(-3)  MUA/cm(2) in control
      compared with 20 mg/mL nicotine at pH 6.5. EIS results exhibited an unexpected
      trend in that the presence of nicotine decreased polarization resistance. This
      suggested a decrease in passive film growth. CONCLUSIONS: At certain
      concentrations, nicotine inhibits local corrosion; however, it also prevents the
      formation of a protective oxide film.

PMID- 25066432
TI  - Everyday emotional experience of adults with attention deficit hyperactivity
      disorder: evidence for reactive and endogenous emotional lability.
AB  - BACKGROUND: Emotional lability (EL), characterized by negative emotional traits
      and emotional instability, is frequently reported in children and adults with
      attention deficit hyperactivity disorder (ADHD). However, EL is primarily
      assessed using retrospective self-report, which is subject to reporting bias and
      does not consider the potential influence of positive and negative everyday
      experiences. METHOD: Ambulatory assessment was carried out in 41 men with ADHD
      without co-morbidity, current medication or substance abuse, and 47 healthy
      control participants. Reports of negative and positive emotions (irritability,
      frustration, anger, happiness, excitement) and the occurrence of bad and good
      events were completed eight times daily during a working week. Group differences
      in emotional intensity and instability were investigated using multilevel models,
      and explored in relation to bad and good events and the Affective Lability Scale 
      Short Form (ALS-SF), an EL questionnaire. RESULTS: The ADHD group reported
      significantly more frequent bad events, heightened intensity and instability of
      irritability and frustration, and greater intensity of anger. The results for
      positive emotions were equivocal or negative. Bad events significantly
      contributed to the intensity and instability of negative emotions, and showed a
      stronger influence in the ADHD group. However, covariation for their effect did
      not eliminate group differences. Small-to-moderate correlations were seen between
      intensity and instability of negative emotions and the ALS-SF. CONCLUSIONS:
      Adults with ADHD report heightened intensity and instability of negative emotions
      in daily life. The results suggest two components of EL in ADHD: a reactive
      component responsive to bad events and an endogenous component, independent of
      negative everyday events.

PMID- 25066435
TI  - Multilocus VNTR analysis-ompA typing of venereal isolates of Chlamydia
      trachomatis in Japan.
AB  - In this study, we investigated the prevalence of genital Chlamydia trachomatis
      isolated in Japan using a high-resolution genotyping method, the multilocus VNTR
      analysis (MLVA)-ompA typing method. Seventeen serotypes of C. trachomatis
      standard strain (A-L3) and 44 clinical isolates were obtained from clinical
      settings. Genotyping of the ompA gene allowed clinical isolates to be divided
      into nine serotypes: B (6.8%), D (15.9%), E (25%), F (20.5%), G (18.1%), H
      (6.8%), Ia (2.3%), J (2.3%), and K (2.3%). These isolates were further divided
      into 28 types after combining ompA genotyping data with MLVA data (Hunter-Gaston
      discriminatory index D, 0.949). Thus, our results demonstrated that MLVA could
      identify clinical isolates that could not be distinguished by ompA typing. 

PMID- 25066434
TI  - Serum (1 -> 3) beta-D-glucan assay for discrimination between Pneumocystis
      jirovecii pneumonia and colonization.
AB  - Polymerase chain reaction (PCR) technique is being increasingly used for the
      microbiological diagnosis of Pneumocystis pneumonia (PCP). As PCR is highly
      sensitive, it can be positive even in a patient with Pneumocystis colonization.
      In this study, we evaluated whether the beta-d-glucan assay could be used to
      differentiate between PCP and Pneumocystis jirovecii colonization in
      immunocompromised patients with pulmonary infiltrates. We retrospectively
      evaluated data from 166 consecutive patients who underwent bronchoalveolar lavage
      for the diagnosis of PCP. Serum levels of beta-d-glucan in the negative,
      colonization, probable PCP, and definite PCP groups were 20.2 +/- 6.3, 48.8 +/-
      15.9, 89.9 +/- 20.2, 224.9 +/- 25.9 pg/mL, respectively. The beta-D-glucan levels
      in the definite PCP group were significantly higher than those in the other 3
      groups (p < 0.001). Serum beta-d-glucan levels in patients with either definite
      or probable PCP (173.1 +/- 18.8 pg/mL) were significantly greater than those in
      patients with colonization who had positive PCR results but improved without anti
      PCP treatment (p < 0.002). The cut-off level for discrimination was estimated to
      be 33.5 pg/mL, with which the positive predictive value was 0.925. These results
      indicate that beta-D-glucan is a useful marker to differentiate between PCP and
      Pneumocystis colonization. A positive beta-D-glucan assay result might be a good
      indication to begin anti-PCP treatment.

PMID- 25066436
TI  - Comment on: temporal changes in glucose homeostasis and incretin hormone response
      at 1 and 6 months following laparoscopic sleeve gastrectomy.

PMID- 25066437
TI  - Acute small bowel obstruction due to the connecting tube of a gastric band.

PMID- 25066438
TI  - Influence of median surgeon operative duration on adverse outcomes in bariatric
      surgery.
AB  - BACKGROUND: Evidence suggests that prolonged operative time adversely affects
      surgical outcomes. However, whether faster surgeons have better outcomes is
      unclear, as a surgeon's speed could reflect skill and efficiency, but may
      alternatively reflect haste. This study evaluates whether median surgeon
      operative time is associated with adverse surgical outcomes after laparoscopic
      Roux-en-Y gastric bypass. METHODS: We performed a retrospective cohort study
      using statewide clinical registry data from the years 2006 to 2012. Surgeons were
      ranked by their median operative time and grouped into terciles. Multivariable
      logistic regression with robust standard errors was used to evaluate the
      influence of median surgeon operative time on 30-day surgical outcomes, adjusting
      for patient and surgeon characteristics, trainee involvement, concurrent
      procedures, and the complex interaction between these variables. RESULTS: A total
      of 16,344 patients underwent surgery during the study period. Compared to
      surgeons in the fastest tercile, slow surgeons required 53 additional minutes to
      complete a gastric bypass procedure (median [interquartile range] 139 [133-150]
      versus 86 [69-91], P<.001). After adjustment for patient characteristic only,
      slow surgeons had significantly higher adjusted rates of any complication,
      prolonged length of stay, emergency department visits or readmissions, and venous
      thromboembolism (VTE). After further adjustment for surgeon characteristics,
      resident involvement, and the interaction between these variables, slow surgeons
      had higher rates of any complication (10.5% versus 7.1%, P=.039), prolonged
      length of stay (14.0% versus 4.4%, P=.002), and VTE (0.39% versus .22%, P<.001).
      CONCLUSION: Median surgeon operative duration is independently associated with
      adjusted rates of certain adverse outcomes after laparoscopic Roux-en-Y gastric
      bypass. Improving surgeon efficiency while operating may reduce operative time
      and improve the safety of bariatric surgery.

PMID- 25066439
TI  - Weight loss and improved quality of life with a nonsurgical endoscopic treatment
      for obesity: clinical results from a 3- and 6-month study.
AB  - BACKGROUND: The TransPyloric ShuttleTM (TPS) is a nonsurgical device that is
      endoscopically delivered to and removed from the stomach to treat obesity. The
      device consists of a large spherical bulb connected to a smaller cylindrical bulb
      by a flexible tether. The larger bulb prevents migration from the stomach, while
      the smaller bulb passes freely into the duodenum to position the TPS across the
      pylorus. Transpyloric positioning may delay gastric emptying, reducing caloric
      intake and enabling weight loss. The purpose of this feasibility study was to
      evaluate the safety and efficacy of the clinical procedure and device. METHODS:
      Twenty patients with a mean body mass index (BMI) of 36.0 kg/m(2) were assigned
      to 2 groups of 10 patients scheduled to have the device for 3 or 6 months.
      Primary outcomes included % excess weight loss (%EWL), % excess BMI loss
      (%EBMIL), % weight loss (%WL), and adverse events. RESULTS: Devices were deployed
      and retrieved in all patients with no complications. Three-month patients had
      mean %EWL of 25.1%, mean %EBMIL of 33.1%, and mean %WL of 8.9%. Six-month
      patients had mean %EWL of 41.0%, mean %EBMIL of 50.0%, and mean %WL of 14.5%.
      Early device removal occurred in 2 patients due to symptomatic gastric
      ulcerations, which resolved after device removal. CONCLUSIONS: The TPS is a
      promising technology that provides a, nonsurgical, ambulatory method for weight
      loss.

PMID- 25066440
TI  - Long-term results after laparoscopic adjustable gastric banding: a mean fourteen
      year follow-up study.
AB  - BACKGROUND: For over a decade, the laparoscopic adjustable gastric band (LAGB)
      was 1 of the most performed bariatric procedures in Europe. This study is a
      retrospective analysis with prospectively collected data of the experience in 1
      specialized Dutch center with the adjustable gastric band over 14 years. METHODS:
      Between 1995 and 2003, 201 patients underwent an LAGB for morbid obesity in our
      hospital. Data on preoperative clinical characteristic, postoperative outcome and
      weight loss patterns, and co-morbidities for up to 18 years are presented and
      evaluated using the Bariatric Analysis and Reporting Outcome System (BAROS).
      RESULTS: Average follow-up was 13.6 (+/- 2.0) years (163 mo) and 99% of patients
      with complete follow-up. Two thirds of patients reached an excess weight loss
      (EWL)>50% at some point after LAGB placement. However, due to insufficient weight
      loss or complications in 53% of patients, the LAGB had to be removed or converted
      to a Roux-en-Y gastric bypass. Additionally, half of the remaining patients had
      disappointing results according to the BAROS score. In total, less than one
      quarter (22%) of patients had a functioning band with a good result after the
      follow-up period. Although initially the number of patients experiencing co
      morbidities was reduced, most of them returned and a large number of patients
      developed new co-morbidities. Complications, other than weight regain, were
      numerous as 47% of patients experienced at least 1. In total, 204 reoperations
      were performed in 137 (68%) patients. Furthermore, patients who were lost to
      follow-up did almost twice as bad in terms of EWL compared to patients who had
      regular follow-up. CONCLUSION: Morbid obesity is a chronic disease that can be
      resolved with bariatric surgery. One of the treatment options is the LAGB, which
      in the short term shows good results in terms of EWL and co-morbidity reduction.
      In the long term, however, EWL and co-morbidity reduction are disappointing, and
      the LAGB does not seem to live up to expectations. Besides the decrease in EWL
      over time, the number of reoperations required is alarming. In total, less than a
      quarter of patients still had a functioning band after a mean 14 years of follow
      up.

PMID- 25066441
TI  - Two-step conversion surgery after failed laparoscopic adjustable gastric banding.
      Comparison between laparoscopic Roux-en-Y gastric bypass and laparoscopic gastric
      sleeve.
AB  - BACKGROUND: Despite its worldwide popularity, laparoscopic adjustable gastric
      banding (LAGB) requires revisional surgery for failures or complications, in 20
      60% of cases. The purpose of this study was to compare in terms of efficacy and
      safety, the conversion of failed LAGB to laparoscopic Roux-en-Y gastric bypass
      (LRYGB) and laparoscopic sleeve gastrectomy. (LSG). METHODS: The bariatric
      database of our institution was reviewed to identify patients who had undergone
      conversion of failed LAGB to LRYGB or to LSG, from November 2007 to June 2012.
      RESULTS: A total of 108 patients were included. Of these, 74 (68.5%) underwent
      conversion to LRYGB and 34 to LSG. All of the procedures were performed in 2
      stage and laparoscopically. The mean follow-up for the LRYGB group was 29.1+/
      17.9 months while for the LSG patients was 24.2+/-14.3 months. The mean body mass
      index (BMI) prior LRYGB and LSG was 45.6+/-7.8 and 47.5+/-5.6 (P = .09),
      respectively. Postoperative complications occurred in 16.2% of the LRYGB patients
      and in 2.9% of the LSG group (P = .04). Mean percentage of excess weight loss was
      59.9%+/-16.2% and 70.2%+/-16.7% in LRYGB, and it was 52.2%+/-11.4% and 59.9%+/
      14.4% in LSG at 12 months (P = .007) and 24 months (P = .01) after conversion.
      CONCLUSION: In this series, LRYGB and LSG are both effective and adequate
      revisional procedure after failure of LAGB. While LRYGB seems to ensure greater
      weight loss at 24 months follow-up, LSG is associated with a lower postoperative
      morbidity.

PMID- 25066442
TI  - Laparoscopic gastric greater curvature plication versus laparoscopic sleeve
      gastrectomy: early outcome in 140 patients.
AB  - BACKGROUND: Laparoscopic gastric greater curvature plication (LGGCP) is a novel
      bariatric procedure. Its outcome as a standalone procedure has been studied in
      the literature. We herein describe a comparative study between LGGCP versus
      laparoscopic sleeve gastrectomy (LSG). The objective of this study was to analyze
      %excess weight loss (%EWL), co-morbidity improvement and complication rate in
      both groups at 1, 3, 6, 12 months follow-up. METHODS: Retrospective study of 140
      patients undergoing LGGCP and LSG between July 2011 and March 2012 at University
      of Alexandria, Egypt. Data on patient demography, operative time, length of stay,
      body mass index (BMI) were collected. RESULTS: Baseline characteristics were
      similar for both groups, except for preoperative BMI that was higher among the
      LSG group. Follow up rate was 98% (n = LGCCP: 68 - LSG: 69) at 6 months and 81%
      (n = LGGCP: 54 - LSG: 60) at 1 year. The mean operative time and mean length of
      stay were longer in the LSG group (P = .03) and (P = .02), respectively. There
      were 4 (6.5%) readmissions and 2 (3.2%) reoperations in the LGGCP group compared
      to 3 (3.8%) readmission and 2 (2.6%) reoperations in the LSG group. At 6 months
      follow-up the mean %EWL for LGGCP and LSG was 40.4+/-11.9% and 47.1+/-13.9%
      (P<.001), while at 1 year it was 52.1+/-15.1% and 68.1+/-15.8% (P<.001),
      respectively. Both techniques showed similar results in co-morbidity improvement
      at 1 year. CONCLUSION: In the short term, both techniques were comparable as
      regards to co-morbidity resolution. However, LSG appears to have achieved a
      higher weight loss.

PMID- 25066444
TI  - Effect of new criteria on the diagnosis of gestational diabetes in women
      submitted to gastric bypass.
AB  - BACKGROUND: Bariatric surgery has been shown to improve many obesity related co
      morbidities, including gestational diabetes mellitus (GDM). Recently, new
      diagnostic criteria for GDM following the International Association of Diabetes
      and Pregnancy Study Group recommendations were implemented. The objective of this
      study was to compare the use of 2 different GDM criteria in diagnostic and
      pregnancy outcome after Roux-en-Y gastric bypass (RYGB). METHODS: Pregnant women
      who had previously undergone RYGB (n = 30) were screened for GDM with Carpenter
      and Coustan (C&C) criteria (n = 18) or the new diagnostic criteria (n = 12).
      RESULTS: None of the patients screened using C&C criteria where diagnosed with
      GDM, while 50% of the patients screened with the new criteria had GDM. Among
      women that underwent oral glucose tolerance tests (OGTT) (n = 19) as required for
      the new diagnostic criteria, 57.9% developed reactive hypoglycemia. All women
      diagnosed with GDM had excellent metabolic control during pregnancy and comparing
      the outcome of these pregnancies and those of women without GDM, there were no
      significant differences regarding the age at time of surgery or at pregnancy,
      body mass index before surgery and pregnancy, parity, previous history of GDM,
      time from surgery to conception, weight lost until pregnancy, weight gain during
      pregnancy, gestational age at delivery, and birth weight adjusted for gestational
      age. CONCLUSION: New GDM diagnostic criteria in post-RYGB pregnant women
      increased the prevalence of GDM diagnostic without changing pregnancy outcomes.
      In addition, OGTTs were associated with a high rate of reactive hypoglycemia.
      These data suggest that alternative GDM diagnostic criteria are needed for these
      postbariatric patients.

PMID- 25066445
TI  - Roux-en-Y gastric bypass as metabolic treatment in a heart transplant patient
      with type 2 diabetes: 4 years later.

PMID- 25066443
TI  - Predictors and correlates of follow-up visit adherence among adolescents
      receiving laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Adherence behaviors have not been examined among adolescents
      undergoing laparoscopic adjustable gastric banding (LAGB). In addition, studies
      of youth receiving bariatric surgery have not considered the influence of
      psychopathology on postoperative adherence. The purpose of this study was to
      evaluate predictors and correlates of adherence to post-surgery visits among a
      sample of adolescents undergoing LAGB. METHODS: Postoperative visits with
      surgical staff were analyzed over the 2 years after surgery (n = 101
      adolescents). Growth mixture modeling examined trends in adherence. RESULTS: A 3
      class solution provided the best fit to the data. The classes from the final
      model were characterized by class 1 (61.6%) demonstrating high levels of
      adherence over the 24 months after LAGB, class 2 (28.5%) showing a more gradual
      decline in adherence, and class 3 (9.9%) with an accelerated decline in
      adherence. Higher levels of preoperative depressive symptoms and more
      preoperative episodes of loss of control overeating decreased the likelihood of
      adherence. Class 3 adolescents had significantly higher estimated 24-month body
      mass indices than classes 1 or 2. CONCLUSION: Variable patterns of follow-up
      visit adherence were identified among adolescents receiving LAGB, which were
      predicted by depressive symptoms and loss of control overeating. The trajectory
      characterized by a rapid decline in adherence to follow-up visits was also
      associated with less weight loss.

PMID- 25066447
TI  - Effects of cryopreservation on human mesenchymal stem cells attached to different
      substrates.
AB  - There is a need to preserve cell-seeded scaffolds or cell-matrix constructs for
      tissue-engineering and other applications. Cryopreservation is likely to be the
      most practical method. The aim of this study was to investigate how
      cryopreservation affects cells attached to different substrates and how they
      respond differently from those in suspension. Human mesenchymal stem cells
      (hMSCs) were studied for their close relevance to tissue-engineering and stem
      cell therapy applications, in particular how cryopreservation affects cell
      adherence, cell growth and the viability of hMSCs attached to different
      substrates, including glass, gelatin, matrigel and a matrigel sandwich. The
      effects of cryopreservation on F-actin organization, intracellular pH and
      mitochondrial localization of the adherent hMSCs were further investigated. It
      was found that cells attached to a glass surface could hardly survive the common
      cryopreservation protocol using 10% DMSO and a 1 degrees C/min cooling rate. By
      contrast, cells attached to gelatin and matrigel could survive to a greater
      extent. Furthermore, cryopreservation affected the potential of cell attachment
      and proliferation, resulted in distortion of F-actin, led to alteration of
      intracellular pH of the hMSCs for all tested substrates and caused a change in
      the mitochondrial localization of hMSCs on a matrigel substrate and in a matrigel
      sandwich. Our results showed that cell attachment and cell viability could be
      improved by changing the interaction between cell and substrate through
      modification of the substrate properties, which has implications for scaffold
      design if cell-seeded scaffolds or engineered tissues need to be cryopreserved.

PMID- 25066448
TI  - Parallels in preschoolers' and adults' judgments about ownership rights and
      bodily rights.
AB  - Understanding ownership rights is necessary for socially appropriate behavior. We
      provide evidence that preschoolers' and adults' judgments of ownership rights are
      related to their judgments of bodily rights. Four-year-olds (n = 70) and adults
      (n = 89) evaluated the acceptability of harmless actions targeting owned property
      and body parts. At both ages, evaluations did not vary for owned property or body
      parts. Instead, evaluations were influenced by two other manipulations-whether
      the target belonged to the agent or another person, and whether that other person
      approved of the action. Moreover, these manipulations influenced judgments for
      owned objects and body parts in the same way: When the other person approved of
      the action, participants' judgments were positive regardless of who the target
      belonged to. In contrast, when that person disapproved, judgments depended on who
      the target belonged to. These findings show that young children grasp the
      importance of approval or consent for ownership rights and bodily rights, and
      likewise suggest that people's notions of ownership rights are related to their
      appreciation of bodily rights. 

PMID- 25066446
TI  - Plasma insulin, C-peptide and blood glucose and the risk of gastric cancer: the
      Japan Public Health Center-based prospective study.
AB  - To date, the association between diabetes mellitus (DM) and gastric cancer has
      been controversial, including the underlying mechanism. We investigated the
      association between plasma diabetic biomarkers (insulin, C-peptide, and blood
      glucose) and gastric cancer risk. In addition, homeostasis model assessment of
      insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell
      function (HOMA-beta) were calculated. A total of 36,745 subjects aged 40-69 years
      in the Japan Public Health Center-based prospective study (JPHC) who returned the
      baseline questionnaire and provided blood samples were followed from 1990 to
      2004. In the present analysis, 477 cases and 477 matched controls were used. The
      odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for
      developing gastric cancer were calculated using conditional logistic regression
      models. Plasma insulin was positively associated with increased risk of gastric
      cancer; compared to tertile 1, ORs were 1.69 (95% CI = 1.11-2.59) and 2.01 (1.19
      3.38) for tertiles 2 and 3, respectively (p for trend = 0.009). In men, C-peptide
      was also positively associated with a significant risk; corresponding ORs were
      1.42 (0.85-2.38) and 1.91 (1.03-3.54), respectively (p for trend = 0.04). These
      findings were confirmed for blood samples from the fasting group (>=8 hr after a
      meal). Higher HOMA-IR was also associated with increased risk, whereas no
      association was observed for blood glucose. Our findings suggest that Japanese
      population with higher insulin and C-peptide levels derived from insulin
      resistance have an elevated risk of gastric cancer.

PMID- 25066449
TI  - Neural substrates of impulsive decision making modulated by modafinil in alcohol
      dependent patients.
AB  - BACKGROUND: Impulsive decision making is a hallmark of frequently occurring
      addiction disorders including alcohol dependence (AD). Therefore, ameliorating
      impulsive decision making is a promising target for the treatment of AD. Previous
      studies have shown that modafinil enhances cognitive control functions in various
      psychiatric disorders. However, the effects of modafinil on delay discounting and
      its underlying neural correlates have not been investigated as yet. The aim of
      the current study was to investigate the effects of modafinil on neural
      correlates of impulsive decision making in abstinent AD patients and healthy
      control (HC) subjects. METHOD: A randomized, double-blind, placebo-controlled,
      within-subjects cross-over study using functional magnetic resonance imaging
      (fMRI) was conducted in 14 AD patients and 16 HC subjects. All subjects
      participated in two fMRI sessions in which they either received a single dose of
      placebo or 200 mg of modafinil 2 h before the session. During fMRI, subjects
      completed a delay-discounting task to measure impulsive decision making. RESULTS:
      Modafinil improved impulsive decision making in AD pateints, which was
      accompanied by enhanced recruitment of frontoparietal regions and reduced
      activation of the ventromedial prefrontal cortex. Moreover, modafinil-induced
      enhancement of functional connectivity between the superior frontal gyrus and
      ventral striatum was specifically associated with improvement in impulsive
      decision making. CONCLUSIONS: These findings indicate that modafinil can improve
      impulsive decision making in AD patients through an enhanced coupling of
      prefrontal control regions and brain regions coding the subjective value of
      rewards. Therefore, the current study supports the implementation of modafinil in
      future clinical trials for AD.

PMID- 25066450
TI  - Ascertainment of acute liver injury in two European primary care databases.
AB  - PURPOSE: The purpose of this study was to ascertain acute liver injury (ALI) in
      primary care databases using different computer algorithms. The aim of this
      investigation was to study and compare the incidence of ALI in different primary
      care databases and using different definitions of ALI. METHODS: The Clinical
      Practice Research Datalink (CPRD) in UK and the Spanish "Base de datos para la
      Investigacion Farmacoepidemiologica en Atencion Primaria" (BIFAP) were used. Both
      are primary care databases from which we selected individuals of all ages
      registered between January 2004 and December 2009. We developed two case
      definitions of idiopathic ALI using computer algorithms: (i) restrictive
      definition (definite cases) and (ii) broad definition (definite and probable
      cases). Patients presenting prior liver conditions were excluded. Manual review
      of potential cases was performed to confirm diagnosis, in a sample in CPRD (21%)
      and all potential cases in BIFAP. Incidence rates of ALI by age, sex and calendar
      year were calculated. RESULTS: In BIFAP, all cases considered definite after
      manual review had been detected with the computer algorithm as potential cases,
      and none came from the non-cases group. The restrictive definition of ALI had a
      low sensitivity but a very high specificity (95% in BIFAP) and showed higher
      rates of agreement between computer search and manual review compared to the
      broad definition. Higher incidence rates of definite ALI in 2008 were observed in
      BIFAP (3.01 (95% confidence interval (CI) 2.13-4.25) per 100,000 person-years
      than CPRD (1.35 (95% CI 1.03-1.78)). CONCLUSIONS: This study shows that it is
      feasible to identify ALI cases if restrictive selection criteria are used and the
      possibility to review additional information to rule out differential diagnoses.
      Our results confirm that idiopathic ALI is a very rare disease in the general
      population. Finally, the construction of a standard definition with predefined
      criteria facilitates the timely comparison across databases.

PMID- 25066451
TI  - Consequences of dextropropoxyphene market withdrawal in elderly patients with
      chronic pain.
AB  - OBJECTIVE: Describe the consequences of dextropropoxyphene (DXP) market
      withdrawal on analgesic prescriptions and on the quality of therapeutic
      management of chronic pain. PATIENTS AND METHODS: From a cohort of non
      institutionalised elderly patients with chronic pain recruited by general
      practitioners, we selected patients who were treated with DXP daily for at least
      6 months just prior to DXP market withdrawal and who had an evaluation of pain
      and its impact on daily activities before and after DXP withdrawal. RESULTS: One
      hundred three patients took DXP daily for chronic pain. Immediately after DXP
      market withdrawal, 42 (40.8%), 55 (53.4%) and 3 (2.9%) patients were treated with
      step 1, 2 and 3 analgesics, respectively, and 3 patients (2.9%) were no longer
      receiving any analgesic medication. Among the 55 patients who continued on step 2
      analgesics, 37 were treated with tramadol, 14 with codeine and 9 with opium. Pain
      intensity and the impact of pain on daily activities remained stable. CONCLUSION:
      DXP market withdrawal had no consequences on the intensity or impact of chronic
      pain in elderly patients.

PMID- 25066452
TI  - Dietary mercury exposure to endangered California Clapper Rails in San Francisco
      Bay.
AB  - California Clapper Rails (Rallus longirostris obsoletus) are an endangered
      waterbird that forage in tidal-marsh habitats that pose risks from mercury
      exposure. We analyzed total mercury (Hg) in six macro-invertebrate and one fish
      species representing Clapper Rail diets from four tidal-marshes in San Francisco
      Bay, California. Mercury concentrations among individual taxa ranged from lowest
      at Colma Creek (mean range: 0.09-0.2 MUg/g dw) to highest at Cogswell (0.2-0.7),
      Laumeister (0.2-0.9) and Arrowhead Marshes (0.3-1.9). These spatial patterns for
      Hg matched patterns reported previously in Clapper Rail blood from the same four
      marshes. Over 25% of eastern mudsnails (Ilyanassa obsolete) and staghorn sculpin
      (Leptocottus armatus) exceeded dietary Hg concentrations (ww) often associated
      with avian reproductive impairment. Our results indicate that Hg concentrations
      vary considerably among tidal-marshes and diet taxa, and Hg concentrations of
      prey may provide an appropriate proxy for relative exposure risk for Clapper
      Rails.

PMID- 25066453
TI  - Antibiotic resistance of Vibrio harveyi isolated from seawater in Korea.
AB  - Vibrio harveyi is an opportunistic human pathogen that may cause gastroenteritis,
      severe necrotizing soft-tissue infections, and primary septicemia, with a
      potentially high rate of lethality. In this study, we isolated and characterized
      V. harveyi from seawater collected from the West Sea in Korea, including sites
      located near shellfish farms. For the initial isolation of putative V. harveyi,
      isolates were incubated on thiosulfate citrate bile salt sucrose agar plates for
      24h, followed by selection of greenish colonies. Gram-negative and oxidase
      positive colonies were subsequently confirmed by biochemical assays and the API
      20E kit test system. Species-specific 16S rRNA and hemolysin genes were used to
      design V. harveyi-specific PCR primers. From 840 seawater samples, a total of 2
      strains of V. harveyi were isolated from shellfish farm seawater. The two
      isolates were subjected to profiling against 16 antibiotics and found to be
      resistant to cephalothin, vancomycin, ampicillin, cefepime, cefotetan, and
      streptomycin. 

PMID- 25066454
TI  - Factors influencing variability of mercury input to the southern Baltic Sea.
AB  - The southern Baltic countries have been identified as significant sources of Hg
      into the sea. Are anthropogenic activities the sole source? How do meteorological
      parameters influence the deposition? Studies on input of Hg to the Baltic were
      conducted in 2008-2012 in the Polish coastal stations. The riverine load was
      found to depend directly or indirectly on the amount of precipitation and
      catchment type. Input of atmospheric Hg increased along with the number of
      precipitation episodes from remote maritime air masses, as well as with the
      number of days when continental air masses from regional (when domestic heating
      prevailed) and remote sources moved over the Baltic, during the heating season.
      During the non-heating season metal input was found to be proportional to
      episodes of rain from continental regional air masses and to the number of days
      under influence of continental and maritime air masses from regional sources. 

PMID- 25066455
TI  - Lethal lesions and amputation caused by plastic debris and fishing gear on the
      loggerhead turtle Caretta caretta (Linnaeus, 1758). Three case reports from
      Terceira Island, Azores (NE Atlantic).
AB  - In this note we report and discuss three cases involving two serious injuries and
      one death on three specimens of the loggerhead turtle Caretta caretta, found in
      Terceira Island, Azores (NE Atlantic). Plastic debris and lost/discarded fishing
      gear caused these accidents. In fact, these types of marine litter are known to
      cause several accidents all over the world involving many taxa. However, we think
      that this issue has probably a much wider impact and detected cases such as those
      reported here are but just a small sample of the whole unknown dimension of this
      serious marine pollution problem. 

PMID- 25066456
TI  - Tissue distribution and fate of persistent organic pollutants in Indo-Pacific
      humpback dolphins from the Pearl River Estuary, China.
AB  - Eleven persistent organic pollutant (POP) compounds including ?PCBs, ?DDTs,
      ?HCHs, aldrin, mirex, endrin, ?CHLs, dieldrin, HCB, heptachlor and
      pentachlorobenzene were measured in the kidney, liver, muscle, melon and other
      tissues of Sousa chinensis stranded on the western coast of the Pearl River
      Estuary in China during 2007-2013. For most parameters of POPs measured, melon
      tissues contained the highest mean concentrations with the exception of aldrin,
      which was higher in the kidney and liver tissues. The concentrations of PCBs,
      DDTs, heptachlor and endrin in the melon tissue exhibited significant
      correlations with body length, whereas PCBs and heptachlor also displayed
      significant regression with age. Our studies showed hepatic concentrations of
      ?DDTs, ?HCHs and mirex in S. chinensis were generally higher than those found in
      cetaceans from other geographic locations. The high levels of POP residues in the
      testis of one male dolphin suggested an increasing risk of infertility in the
      species. 

PMID- 25066457
TI  - Elevated mercury levels in a wintering population of common eiders (Somateria
      mollissima) in the northeastern United States.
AB  - In North America and Europe, sea ducks are important indicators of ecological
      health and inshore marine pollution. To explore spatial variation in mercury
      accumulation in common eiders in the northeastern United States, we compared
      concentrations of total mercury in common eider blood at several New England
      locations between 1998 and 2013. Eider food items (mollusks) were collected and
      analyzed to determine if mercury concentrations in eider blood were indicative of
      local mercury bioavailability. Eiders from Plum Island Sound, MA had a
      significantly higher mean blood mercury concentration (0.83 MUg/g) than those in
      other locations. Mean mercury levels in this population were also nearly three
      times higher than any blood mercury concentrations reported for common eiders in
      published literature. We observed consistent patterns in eider blood mercury and
      blue mussel mercury concentrations between sites, suggesting a tentative
      predictive quality between the two species.

PMID- 25066458
TI  - A centennial record of anthropogenic impacts and extreme weather events in
      southwestern Taiwan: evidence from sedimentary molecular markers in coastal
      margin.
AB  - A 100-year history of human and natural disturbances in southwestern Taiwan was
      reconstructed using a suite of molecular markers in four dated sediment cores
      from the upper slope region off the Gaoping River mouth. Trends in polycyclic
      aromatic hydrocarbons (PAHs) tracked Taiwan's industrialization/urbanization
      starting in the 1970s, and the enactment of environmental regulatory policies
      thereafter. The predominant pyrogenic sources include vehicular, smelter, and
      coal combustion but spatial differences are observed among sub-regions of the
      shelf. Profiles of lignin oxidation products (LOPs) point to a significant
      increase in terrestrial organic matter inputs driven by land development after
      the 1970s. Low lignin diagenetic signature ratios [(Ad/Al)v] in all sediments
      suggest quick transport of fresh plant material from land to sea via mountainous
      rivers. Shifts in PAHs, LOPs, and radionuclides in recent sediments reveal the
      deposition of turbidites resulting from typhoon-induced floods. Multiproxy
      analysis illustrates the interplay between anthropogenic activities and natural
      processes. 

PMID- 25066460
TI  - Artificial selection on larval growth curves in Tribolium: correlated responses
      and constraints.
AB  - Body size is often constrained from evolving. Although artificial selection on
      body size in insects frequently results in a sizable response, these responses
      usually bear fitness costs. Further, these experiments tend to select only on
      size at one landmark age, rather than selecting for patterns of growth over the
      whole larval life stage. To address whether constraints may be caused by larval
      growth patterns rather than final size, we implemented a function-valued (FV)
      trait method of selection, in which entire larval growth curves from Tribolium
      were artificially selected. The selection gradient function used was previously
      predicted to give the maximal response and was implemented using a novel
      selection index in the FV framework. Results indicated a significant response
      after one generation of selection, but no response in subsequent generations.
      Correlated responses included increased mortality, increased critical weight, and
      decreased development time (DT). The lack of response in size and development
      time after the first generation was likely caused by increased mortality suffered
      in selected lines; we demonstrated that the selection criterion caused both
      increased body size and increased mortality. We conclude that artificial
      selection on continuous traits using FV methods is very efficient and that the
      constraint of body size evolution is likely caused by a suite of trade-offs with
      other traits. 

PMID- 25066459
TI  - Measurement of parasitological data by quantitative real-time PCR from controlled
      human malaria infection trials at the Walter Reed Army Institute of Research.
AB  - BACKGROUND: The use of quantitative real-time PCR (qPCR) has allowed for precise
      quantification of parasites in the prepatent period and greatly improved the
      reproducibility and statistical power of controlled human malaria infection
      (CHMI) trials. Parasitological data presented here are from non-immunized,
      control-challenged subjects who participated in two CHMI trials conducted at the
      Walter Reed Army Institute of Research (WRAIR). METHODS: Standardized sporozoite
      challenge was achieved through the bite of five Anopheles stephensi mosquitoes
      infected with the 3D7clone of the NF54 strain of Plasmodium falciparum. Blood
      smears were scored positive when two unambiguous parasites were found. Analysis
      of parasitological PCR data was performed on log-transformed data using an
      independent sample t-test when comparing the two studies. The multiplication rate
      of blood-stage parasites was estimated using the linear model. RESULTS: On
      average, parasites were detected 4.91 days (95% CI = 4.190 to 5.627) before
      smears. The earliest parasites were detected within 120 hours (5.01 days) after
      challenge. Parasite densities showed consistent cyclic patterns of blood-stage
      parasite growth in all volunteers. The parasite multiplication rates for both
      studies was 8.18 (95% CI = 6.162 to 10.20). Data showed that at low parasite
      densities, a combination of sequestration and stochastic effects of low copy
      number DNA may impact qPCR detection and the parasite detection limit.
      CONCLUSION: Smear positive is an endpoint which antimalarial rescue is imperative
      whereas early detection of parasitological data by qPCR can allow for better
      anticipation of the endpoint. This would allow for early treatment to reduce
      clinical illness and risk for study participants. To use qPCR as the primary
      endpoint in CHMI trials, an algorithm of two positives by qPCR where one of the
      positives must have parasite density of at least 2 parasites/MUL is proposed.

PMID- 25066461
TI  - Substance use and risk of death in young offenders: a prospective data linkage
      study.
AB  - INTRODUCTION AND AIMS: Young offenders are at increased risk of preventable death
      after release from custody, but risk factors for death in this population are
      poorly understood. Despite their poor health profiles, no studies have examined
      mortality outcomes in young people who have served community-based orders. The
      aims of this study were to describe the causes and identify risk factors for
      death in a cohort of young offenders in Victoria, Australia. DESIGN AND METHODS:
      We interviewed young people serving a custodial (n = 273) or community-based
      order (n = 242) in Victoria, Australia in 2002-2003. Measures included
      demographics and family history, offence history, experience of victimisation,
      mental illness, self-harm and substance use. Deaths up to 31 December 2011 were
      identified through a probabilistic linkage with the National Death Index.
      RESULTS: The all-cause crude mortality rate was 4.2 (95% confidence interval 2.7
      6.8) per 1000 person years and was not significantly different for those who had
      served custodial and community-based orders. Most deaths were due to drug
      overdose, traffic accidents or suicide. Adjusting for age, sex and order type,
      risk factors for death from the baseline interview included weekly use of
      opioids, sleeping pills or painkillers, polydrug use and injecting drug use.
      DISCUSSION AND CONCLUSIONS: Young people who have served community-based and
      custodial orders are at an increased risk of preventable death. Those engaging in
      risky substance use, particularly injecting drug use and use of multiple central
      nervous system depressants, are at greatest risk. There is an urgent need to
      develop and rigorously evaluate preventive interventions.

PMID- 25066462
TI  - Brain network science needs to become predictive. Comment on "Understanding brain
      networks and brain organization" by Luiz Pessoa.

PMID- 25066463
TI  - Orthogonally engineering matrix topography and rigidity to regulate multicellular
      morphology.
AB  - Programmable polymer substrates, which mimic the variable extracellular matrices
      in living systems, are used to regulate multicellular morphology, via
      orthogonally modulating the matrix topography and elasticity. The multicellular
      morphology is dependent on the competition between cell-matrix adhesion and cell
      cell adhesion. Decreasing the cell-matrix adhesion provokes cytoskeleton
      reorganization, inhibits lamellipodial crawling, and thus enhances the leakiness
      of multicellular morphology. 

PMID- 25066464
TI  - IL-34 and macrophage colony-stimulating factor are overexpressed in hepatitis C
      virus fibrosis and induce profibrotic macrophages that promote collagen synthesis
      by hepatic stellate cells.
AB  - Chronic hepatitis C virus (HCV) infection is characterized by progressive hepatic
      fibrosis, a process dependent on monocyte recruitment and accumulation into the
      liver. The mediators expressed in chronically injured liver that control the
      differentiation of human monocytes into profibrotic macrophages (Mphi) remain
      poorly defined. We report that chronically HCV-infected patients with high
      fibrosis stages have higher serum levels of macrophage colony-stimulating factor
      (M-CSF) and interleukin (IL)-34 than HCV-infected patients with lower fibrosis
      stages and healthy subjects. Immunohistochemistry reveals an intense expression
      of IL-34 and M-CSF by hepatocytes around liver lesions. In addition, HCV
      infection and inflammatory cytokines enhance the in vitro production of IL-34 and
      M-CSF by hepatocytes. We next analyzed the acquisition of profibrotic properties
      by Mphi generated with M-CSF (M-CSF-Mphi) or IL-34 (IL-34-Mphi). M-CSF and IL-34
      up-regulate the expression, by differentiating monocytes, of chemokine (C-C
      motif) ligand (CCL)2, CCL4, C-C chemokine receptor (CCR)1, and CCR5, which are
      involved in monocyte recruitment/Mphi accumulation in liver lesions. M-CSF-Mphi
      and IL-34-Mphi also express the hepatic stellate cell (HSC) activators, platelet
      derived growth factor, transforming growth factor beta, and galectin-3. IL-34
      Mphi and M-CSF-Mphi induce type I collagen synthesis by HSCs, the main collagen
      producing cells in liver fibrosis. IL-13, whose expression correlates with the
      fibrosis stage in HCV-infected patients, decreases the expression of the
      collagenase, matrix metalloproteinase 1, by IL-34-Mphi and M-CSF-Mphi, thereby
      enhancing collagen synthesis. By inhibiting the production of interferon-gamma
      (IFN-gamma) by activated natural killer cells, IL-34-Mphi and M-CSF-Mphi prevent
      the IFN-gamma-induced killing of HSCs. CONCLUSION: These results identify M-CSF
      and IL-34 as potent profibrotic factors in HCV liver fibrosis.

PMID- 25066465
TI  - The impact of anaemia on functioning in older people in a rural population in
      South West Uganda.

PMID- 25066466
TI  - Insights from interferon-alpha-related depression for the pathogenesis of
      depression associated with inflammation.
AB  - Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that is administered as a
      therapeutic in highly prevalent medical conditions such as chronic hepatitis C
      and B virus infection, melanoma and lymphoma. IFN-alpha induces, to a clinically
      relevant degree, concentration, memory, drive and mood disturbances in almost
      half of all patients. For this reason, IFN-alpha is increasingly being replaced
      by more specifically acting drugs. In the past decades, IFN-alpha has offered a
      valuable insight into the pathogenesis of major depression, particularly in
      settings associated with inflammation. IFN-alpha triggers immune responses,
      hypothalamo-pituitary-adrenal axis abnormalities and disturbances of brain
      metabolism resembling those in other depression states. IFN-alpha stimulates
      indoleamine-2,3 dioxygenase-1, activating the kynurenine pathway with reduced
      formation of the neurotransmitters serotonin and dopamine, excessive formation of
      the NMDA agonist quinolinic acid, and reduced formation of the NMDA antagonist
      kynurenic acid. In addition, IFN-alpha disturbs neurotrophic signaling and
      impedes neurite outgrowth, synaptic plasticity, endogenous neurogenesis and
      neuronal survival. Consequently, IFN-alpha-related depression may represent a
      model for the neurodegenerative changes that are noticed in late-life major
      depression. Indeed, the observation that brain responses in IFN-alpha-related
      depression resemble idiopathic depression is supported by the existence of common
      genetic signatures, among which of note, a number of neuronal survival and
      plasticity genes have been identified. In view of the high incidence of
      depressive symptoms, IFN-alpha-related depression is an attractive model for
      studying links between neuronal plasticity, neurodegeneration and depression. We
      predict that in the latter areas new targets for anti-depressant therapies could
      be identified, which may deepen our understanding of idiopathic major depression.

PMID- 25066468
TI  - Cocaine use and risk of stroke: a systematic review.
AB  - BACKGROUND: Both cocaine use and strokes impact public health. Cocaine is a
      putative cause of strokes, but no systematic review of the scientific evidence
      has been published. METHODS: All relevant bibliographic-databases were searched
      until January 2014 for articles on the epidemiological association between
      cocaine use and strokes. Search strings were supervised by expert librarians.
      Three researchers independently reviewed studies for inclusion and data
      extraction following STROBE recommendations. Quality appraisal included study
      validity and bias. Both ischemic and hemorrhagic strokes were considered.
      RESULTS: Of 996 articles, 9 were selected: 7 case-control studies (CCS) and 2
      cross-sectional (CSS) studies. One CCS (aOR=6.1; 95% CI: 3.3-11.8) and one CSS
      (aOR=2.33; 95% CI: 1.74-3.11) showed an association between cocaine and
      hemorrhagic strokes. The latter study also found a positive relationship with
      ischemic stroke (aOR=2.03; 95% CI: 1.48-2.79). Another CCS found the exposure to
      be associated with stroke without distinguishing between types (aOR=13.9; 95% CI:
      2.8-69.4). One forensic CCS found that deaths with cocaine-positive toxicology
      presented a 14.3-fold (95% CI: 5.6-37) and 4.6-fold (95% CI: 2.5-8.5) increased
      risk of atherosclerosis compared to opioid-related deaths and hanging-deaths
      respectively. One CCS did not provide an aOR but found a statistically
      significant association between cocaine and hemorrhagic stroke. Three CCS and one
      CSS did not find any relationship between cocaine and strokes. Inadequate control
      for confounding was not uncommon. CONCLUSIONS: Epidemiological evidence suggests
      that cocaine use increases the risk of stroke. Larger, more rigorous
      observational studies, including cohort approaches, are needed to better quantify
      this risk, and should consider stroke type, hypertension variation,
      frequency/length of cocaine use, amphetamines co-use, and other factors.

PMID- 25066469
TI  - Prodromal dementia with Lewy bodies.
AB  - BACKGROUND: The clinical condition of dementia is now recognized as a diagnosis
      that can only be applied too late in the disease process to be useful for
      therapeutic approaches centring on disease modification. As a result, in recent
      years increasing attention has been given to mild cognitive impairment (MCI) and
      the diagnosis of prodromal dementia. This paper reviews the evidence for the
      clinical presentation of prodromal dementia with Lewy bodies (DLB). METHOD: A
      Medline search was carried out to identify articles with original data on the
      prodromal presentation of DLB. RESULTS: In MCI cohorts that progress to dementia,
      the proportion diagnosed with DLB is similar to that reported in dementia
      cohorts. Prodromal DLB may present as any MCI subtype, although visuospatial and
      executive domains may be most commonly affected. Rapid eye movement (REM) sleep
      behaviour disorder (RBD), autonomic symptoms, hyposmia, hallucinations and motor
      symptoms seem to be more common in prodromal DLB than in prodromal Alzheimer's
      disease (AD). Some of these symptoms can precede the diagnosis of DLB by several
      years. There has been little research into the use of biomarkers in prodromal
      DLB, although in RBD cohorts, clinical and imaging biomarkers have been
      associated with the development of DLB. CONCLUSIONS: The evidence available
      suggests that prodromal DLB may be differentiated from other dementia prodromes
      in most cases. Further research is needed to confirm this, and to assess the
      utility of biomarkers such as 123I-FP-CIT and 123I-MIBG imaging.

PMID- 25066467
TI  - Perinatal depression and child development: exploring the economic consequences
      from a South London cohort.
AB  - BACKGROUND: Depression in mothers during pregnancy and in the postnatal period
      has been recognized to have wide-ranging adverse impacts on offspring. Our study
      examines some of the outcomes and long-term economic implications experienced by
      offspring who have been exposed to perinatal depression. METHOD: We analysed the
      effects of perinatal depression on child development outcomes of children at ages
      11 and 16 years from the community-based South London Child Development Study.
      Economic consequences were attached to those outcomes through simple decision
      analytic techniques, building on evidence from studies of epidemiology, health
      related quality of life, public sector costs and employment. The economic
      analysis takes a life-course perspective from the viewpoints of the public
      sector, individual and society. RESULTS: Additional risks that children exposed
      to perinatal depression develop emotional, behavioural or cognitive problems
      ranged from 5% to 21%. In addition, there was a high risk (24%) that children
      would have special educational needs. We present results in the form of cost
      consequences attached to adverse child outcomes. For each child exposed to
      perinatal depression, public sector costs exceeded L3030, costs due to reduced
      earnings were L1400 and health-related quality of life loss was valued at L3760.
      CONCLUSIONS: Action to prevent or treat mothers' depression during pregnancy and
      after birth is likely to reduce public sector costs, increase earnings and
      improve quality of life for children who were exposed to the condition.

PMID- 25066470
TI  - Dialysis outcomes of elderly Indigenous and non-Indigenous Australians.
AB  - AIM: Whilst increasing numbers of elderly people in Australia are commencing
      dialysis, few Indigenous patients are aged >= 65 years and their outcomes are
      unknown. We compared the long-term survival, mortality hazards and causes of
      death between elderly Indigenous and elderly non-Indigenous dialysis patients.
      METHODS: This was a retrospective cohort study of adults aged >= 65 years who
      commenced dialysis in Australia from 2001-2011, identified from the Australia and
      New Zealand Dialysis and Transplant (ANZDATA) Registry. Indigenous (n = 263) and
      non-Indigenous (n = 10,713) patients were followed until death, loss to follow
      up, recovery of renal function or 31 December 2011. Mortality was compared using
      a multivariate Cox proportional-hazards model with age, gender, body mass index,
      smoking, primary renal disease, comorbidities, late referral and initial
      treatment modality as predictive variables. RESULTS: Median follow-up was 26.9
      months (interquartile range 11.3-48.8 months). Overall 166 Indigenous and 6265
      non-Indigenous patients died during the 11-year follow-up period. Mortality rates
      per 100 patient-years were 23.9 for Indigenous patients and 21.2 for non
      Indigenous patients. The overall 1-, 3- and 5-year survival rates were 81%, 49%
      and 27% for Indigenous patients and 82%, 55% and 35% for non-Indigenous patients
      respectively. Indigenous patients had a 20% increased risk of mortality compared
      with non-Indigenous patients (adjusted hazard ratio 1.20, 95% confidence
      interval, 1.02, 1.41; P = 0.02). 'Social deaths' (predominantly dialysis
      withdrawal) and cardiac deaths were the main causes of death for both groups.
      CONCLUSION: Among elderly dialysis patients in Australia, Indigenous status
      remains an important factor in predicting survival.

PMID- 25066471
TI  - Persistent antimony- and bismuth-centered radicals in solution.
AB  - Stibinyl and bismuthinyl radicals are recognized as representative intermediates
      of antimony and bismuth compounds, but still elusive in the condensed phase. We
      successfully synthesized persistent stibinyl and bismuthinyl radicals in solution
      by facile dissociation of the corresponding dimers with bulky substituents. We
      characterized the radicals by NMR and UV/Vis spectroscopy and estimated the
      thermodynamic parameters for the dissociation equilibria. The radicals show n->p
      (HOMO->SOMO) transition bands at 497 nm (stibinyl) and 543 nm (bismuthinyl) in 3
      methylpentane and react with a stable nitroxyl radical to give the cross-radical
      coupling products in good yields. 

PMID- 25066472
TI  - Ultrasonically triggered ignition at liquid surfaces.
AB  - Ultrasound is considered to be an ignition source according to international
      standards, setting a threshold value of 1mW/mm(2) [1] which is based on
      theoretical estimations but which lacks experimental verification. Therefore, it
      is assumed that this threshold includes a large safety margin. At the same time,
      ultrasound is used in a variety of industrial applications where it can come into
      contact with explosive atmospheres. However, until now, no explosion accidents
      have been reported in connection with ultrasound, so it has been unclear if the
      current threshold value is reasonable. Within this paper, it is shown that
      focused ultrasound coupled into a liquid can in fact ignite explosive atmospheres
      if a specific target positioned at a liquid's surface converts the acoustic
      energy into a hot spot. Based on ignition tests, conditions could be derived that
      are necessary for an ultrasonically triggered explosion. These conditions show
      that the current threshold value can be significantly augmented. 

PMID- 25066473
TI  - Phosphatidylinositol binding of Saccharomyces cerevisiae Pdr16p represents an
      essential feature of this lipid transfer protein to provide protection against
      azole antifungals.
AB  - Pdr16p is considered a factor of clinical azole resistance in fungal pathogens.
      The most distinct phenotype of yeast cells lacking Pdr16p is their increased
      susceptibility to azole and morpholine antifungals. Pdr16p (also known as Sfh3p)
      of Saccharomyces cerevisiae belongs to the Sec14 family of phosphatidylinositol
      transfer proteins. It facilitates transfer of phosphatidylinositol (PI) between
      membrane compartments in in vitro systems. We generated Pdr16p(E235A, K267A)
      mutant defective in PI binding. This PI binding deficient mutant is not able to
      fulfill the role of Pdr16p in protection against azole and morpholine
      antifungals, providing evidence that PI binding is critical for Pdr16 function in
      modulation of sterol metabolism in response to these two types of antifungal
      drugs. A novel feature of Pdr16p, and especially of Pdr16p(E235A, K267A) mutant,
      to bind sterol molecules, is observed. 

PMID- 25066474
TI  - Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential for murine
      CD4(+) T cell metabolic activation.
AB  - Glycerol-3-phosphate acyltransferase-1 is the first rate limiting step in de novo
      glycerophospholipid synthesis. We have previously demonstrated that GPAT-1
      deletion can significantly alter T cell function resulting in a T cell phenotype
      similar to that seen in aging. Recent studies have suggested that changes in the
      metabolic profile of T cells are responsible for defining specific effector
      functions and T cell subsets. Therefore, we determined whether T cell dysfunction
      in GPAT-1 (-/-) CD4(+) T cells could be explained by changes in cellular
      metabolism. We show here for the first time that GPAT-1 (-/-) CD4(+) T cells
      exhibit several key metabolic defects. Striking decreases in both the oxygen
      consumption rate (OCR) and the extracellular acidification rate (ECAR) were
      observed in GPAT-1 (-/-) CD4(+) T cells following CD3/CD28 stimulation indicating
      an inherent cellular defect in energy production. In addition, the spare
      respiratory capacity (SRC) of GPAT-1 (-/-) CD4+ T cells, a key indicator of their
      ability to cope with mitochondrial stress was significantly decreased. We also
      observed a significant reduction in mitochondrial membrane potential in GPAT-1 (
      /-) CD4(+) T cells compared to their WT counterparts, indicating that GPAT-1
      deficiency results in altered or dysfunctional mitochondria. These data
      demonstrate that deletion of GPAT-1 can dramatically alter total cellular
      metabolism under conditions of increased energy demand. Furthermore, altered
      metabolic response following stimulation may be the defining mechanism underlying
      T cell dysfunction in GPAT-1 (-/-) CD4(+) T cells. Taken together, these results
      indicate that GPAT-1 is essential for the response to the increased metabolic
      demands associated with T cell activation. 

PMID- 25066475
TI  - Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the
      horse.
AB  - The aim of the study was to describe the pharmacokinetics and selected
      pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses
      received 5 MUg/kg dexmedetomidine IV. Blood samples were collected before and for
      10 h after drug administration to determine dexmedetomidine plasma
      concentrations. Pharmacokinetic parameters were calculated using noncompartmental
      analysis. Data from one outlier were excluded from the statistical summary.
      Behavioral and physiological responses were recorded before and for 6 h after
      dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly
      (elimination half-life of 8.03 +/- 0.84 min). Time of last detection varied from
      30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26
      +/- 8 and 29 +/- 8 beats/min respectively). Head height decreased by 70% at 4 and
      10 min and gradually returned to baseline. Ability to ambulate was decreased for
      60 min following drug administration, and mechanical nociceptive threshold was
      increased during 30 min. Blood glucose peaked at 30 min (134 +/- 24 mg/dL) and
      borborygmi were decreased for the first hour after dexmedetomidine
      administration. Dexmedetomidine was quickly eliminated as indicated by the rapid
      decrease in plasma concentrations. Physiological, behavioral, and analgesic
      effects observed after dexmedetomidine administration were of short duration.

PMID- 25066476
TI  - Anatomic relationships between the coronary venous system, surrounding
      structures, and the site of origin of epicardial ventricular arrhythmias.
AB  - BACKGROUND: Epicardial left ventricular (LV) idiopathic ventricular arrhythmias
      (VAs) can be approached via the pericardial space, the coronary venous system
      (CVS), or other surrounding structures. The anatomic relationships between
      epicardial sites of origin (SOO) of VAs and surrounding anatomic structures have
      not been systematically described. METHODS AND RESULTS: In 17 patients with
      idiopathic epicardial VAs, the relationships between the SOO and the CVS and
      other neighboring anatomic structures were assessed by computed tomographic
      angiography. Ablation was successful in 12/17 patients (71%). In 10/17 patients,
      the SOO was at a distance of <=4 mm from a coronary artery. The SOO was closer to
      the CVS (2.1 +/- 1.5 mm) than to the pericardial space (9.7 +/- 3.7 mm) or the LV
      endocardium (7.7 +/- 2.7 mm). Successful ablations were carried out from the CVS
      (n = 3), the CVS and LV endocardium (n = 5), the CVS and the aortic cusp (n = 1),
      the CVS, the LV endocardium, and the aortic cusp (n = 1), the LV endocardium (n =
      1), and the CVS and the pericardial space (n = 1). In the remaining 5 patients, a
      subxyphoid pericardial ablation procedure was attempted and failed in all 5
      patients. CONCLUSION: The CVS is closer to the SOO of epicardial idiopathic VAs
      than the pericardial space, the ventricular endocardium, and the aortic cusps.
      Given the proximity to coronary arteries at the SOO, radiofrequency energy often
      cannot be safely delivered to eliminate a VA and ablation may also need to be
      performed from adjacent structures. A subxyphoid pericardial ablation procedure
      has a low probability of success in patients with idiopathic epicardial VAs.

PMID- 25066477
TI  - Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic
      islet transplantation.
AB  - Human islet cell transplantation is a promising treatment for type 1 diabetes;
      however, long-term donor-specific tolerance to islet allografts remains a
      clinically unmet goal. We have previously shown that recipient infusions of
      apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'
      dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term
      acceptance of full major histocompatibility complex (MHC)-mismatched murine islet
      allografts without the use of immunosuppression. In this report, we investigated
      the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as
      a synthetic, cell-free carrier for delivery of donor antigens for the induction
      of transplant tolerance in full MHC-mismatched murine allogeneic islet
      transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg)
      mediated tolerance in ~20% of recipient mice, and the distribution of cellular
      uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg
      mediated the contraction of indirectly activated T cells but did not modulate the
      direct pathway of allorecognition. Combination of PLG-dAg with a short course of
      low dose immunosuppressant rapamycin at the time of transplant significantly
      improved the tolerance efficacy to ~60%. Furthermore, altering the timing of PLG
      dAg administration to a schedule that is more feasible for clinical
      transplantation resulted in equal tolerance efficacy. Thus, the combination
      therapy of PLG-dAg infusions with peritransplant rapamycin represents a
      clinically attractive, biomaterials-based and cell-free method for inducing long
      term donor-specific tolerance for allogeneic cell transplantation, such as for
      allogeneic islet transplantation. 

PMID- 25066478
TI  - Gene-environment interplay between parent-child relationship problems and
      externalizing disorders in adolescence and young adulthood.
AB  - BACKGROUND: Previous studies have shown that genetic risk for externalizing (EXT)
      disorders is greater in the context of adverse family environments during
      adolescence, but it is unclear whether these effects are long lasting. The
      current study evaluated developmental changes in gene-environment interplay in
      the concurrent and prospective associations between parent-child relationship
      problems and EXT at ages 18 and 25 years. METHOD: The sample included 1382 twin
      pairs (48% male) from the Minnesota Twin Family Study, participating in
      assessments at ages 18 years (mean = 17.8, s.d. = 0.69 years) and 25 years (mean
      = 25.0, s.d. = 0.90 years). Perceptions of parent-child relationship problems
      were assessed using questionnaires. Structured interviews were used to assess
      symptoms of adult antisocial behavior and nicotine, alcohol and illicit drug
      dependence. RESULTS: We detected a gene-environment interaction at age 18 years,
      such that the genetic influence on EXT was greater in the context of more parent
      child relationship problems. This moderation effect was not present at age 25
      years, nor did parent-relationship problems at age 18 years moderate genetic
      influence on EXT at age 25 years. Rather, common genetic influences accounted for
      this longitudinal association. CONCLUSIONS: Gene-environment interaction evident
      in the relationship between adolescent parent-child relationship problems and EXT
      is both proximal and developmentally limited. Common genetic influence, rather
      than a gene-environment interaction, accounts for the long-term association
      between parent-child relationship problems at age 18 years and EXT at age 25
      years. These results are consistent with a relatively pervasive importance of
      gene-environmental correlation in the transition from late adolescence to young
      adulthood.

PMID- 25066479
TI  - Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded
      dendritic cells in mice.
AB  - Leukemia immunotherapy frequently does not meet expectation, one of the handicaps
      being tumor exosome (TEX)-promoted immunosuppression. We here asked, using the
      mouse myeloid leukemia WEHI3B and the renal cell carcinoma line RENCA, whether
      dendritic cell (DC) vaccination suffices to counterregulate TEX-induced
      immunosuppression and whether TEX could serve as tumor antigen for DC-loading. DC
      vaccination significantly prolonged the survival time of WEHI3B-bearing mice, TEX
      loaded DC (DC-TEX) being superior to lysate-loaded DC (DC-lys), even an excess of
      TEX not interfering with immune response induction. The superior response to DC
      TEX was accompanied by an increase in WEHI3B-specific CD4+ T cells, evaluated by
      trogocytosis and proliferation. Similar findings accounted for DC loaded with
      RENCA TEX. TEX was efficiently taken-up by DC and TEX uptake supported CD11c,
      MHCII and IL12 upregulation in DC. Importantly, TEX was partly recruited into the
      MHCII-loading compartment such that "TEX" presentation time and recovery in T
      cells significantly exceeded that of tumor-lysate. Thus, TEX did not drive DC
      into a suppressive phenotype and were a superior antigen due to higher efficacy
      of TEX-presentation that is supported by prolonged persistence, preferential
      processing in the MHCII-loading compartment and pronounced trogocytosis by T
      helper cells. TEX is present in tumor patients' sera. TEX, recovered and enriched
      from patients' sera, might well provide an optimized, individual-specific antigen
      source for DC-loading and vaccination.

PMID- 25066480
TI  - Optical coherence tomography applied to tests of skin care products in humans--a
      case study.
AB  - BACKGROUND/PURPOSE: When evaluating skin care products for human skin,
      quantitative test methods need to be simple, precise and reliable. Optical
      coherence tomography (OCT), provides high-resolution sectional images of
      translucent materials to a depth of a few millimeters, a technique usually
      applied to medical measurements in ophthalmology and dermatology. This study
      aimed to demonstrate the application of OCT as the main technique for monitoring
      changes in skin topography during tests of a wrinkle-reduction product in humans.
      METHODS: We used a commercial OCT apparatus to perform clinical examinations of
      skin roughness in treated and non-treated sites in the periorbital region of
      thirty human voluntaries who were using an anti-aging product commercially
      available: Natura Chronos(r) Flavonoides de Passiflora 45+ FPS15, from Natura
      Cosmeticos, Brazil. Measurements were performed days 0, 7, 14 and 28 of
      treatment. Equipment and software allowed real-time recording of skin roughness
      parameters and wrinkle depths. RESULTS: The OCT measurements have allowed the
      monitoring of changes in skin roughness, which have shown reduction in treated
      sites around 10%. The obtained depth distributions also indicate reduction in the
      occurrence of wrinkles deeper than 170 MUm. The verified results are consistent
      with those typically obtained after successful treatment with modern anti-aging
      products. CONCLUSION: By using the OCT technique, it was possible to quantify
      changes in skin roughness and in the distribution of depths of skin wrinkles,
      with adequate sensitivity. OCT imaging allows the direct visualization of the
      skin topography with resolution of micrometers, a reliable and interactive tool
      for clinical use. Therefore, for the first time, we demonstrated the use of OCT
      technique to verify the efficacy of cosmetic products in real time.

PMID- 25066481
TI  - Development of a species-specific PCR assay for identification of the strictly
      anaerobic bacterium Selenomonas lacticifex found in biofilm-covered surfaces in
      brewery bottling halls.
AB  - AIMS: In recent years, beer-spoilage cases from strictly anaerobic bacteria have
      risen in frequency, in connection with the production of non-pasteurized, non
      alcohol and low-alcoholic beers and with the lowering of dissolved oxygen in the
      packaged beer. Selenomonas lacticifex, found in brewer's yeast and in biofilms
      covering some surfaces in brewery bottling area, is considered to be a beer
      spoilage organism. This study aims to develop S. lacticifex-specific PCR assay.
      The objective of this study was also evaluation of the specificity and
      reproducibility of the developed PCR assay in real brewery samples. METHODS AND
      RESULTS: Three primers (one forward and two reverse) were designed for
      identification of the strictly anaerobic bacterium S. lacticifex on the basis of
      the species-specific sequences of the 16S rDNA region. The specificity of the
      primers was tested against 44 brewery-related non-target micro-organisms that
      could potentially occur in the same brewery specimens. None of the primer pairs
      amplified DNA from any of the non-S. lacticifex strains tested including genera
      from the same family (Pectinatus, Megasphaera, Zymophilus) and the closely
      related species Selenomonas ruminantium, showing thus 100% specificity.
      CONCLUSIONS: The PCR assay developed in this study enables the detection of the
      strictly anaerobic bacterium S. lacticifex in real brewery samples including
      pitching yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: Selenomonas lacticifex
      specific PCR assay developed in this study allows for the extension of the
      spectra of detected beer-spoilage micro-organisms in brewing laboratories and
      thus lowering the risk of contamination of the final product.

PMID- 25066482
TI  - Dietary folate intake levels in rural women immediately before pregnancy in
      Northern China.
AB  - BACKGROUND: The study aims to assess dietary folate levels and food sources in
      women immediately before pregnancy in a rural area of northern China associated
      with a high prevalence of neural tube defects. METHODS: Information was collected
      by face-to-face interviews with women who sought premarital healthcare and
      planned to become pregnant within the next 12 months from November 2009 through
      December 2012. Information regarding food consumption was obtained by means of 24
      hr dietary recall. Folate values were assigned to foods according to the China
      Food Composition 2004. Factors associated with dietary folate intake were
      analyzed by multiple linear regression. RESULTS: Mean (+/- standard deviation)
      and median (interquartile range) daily folate intake levels were 114.3 +/- 59.7
      and 102.8 (69.3-146.8) MUg/day, respectively. Over 99% of the subjects had an
      intake level below 320 MUg/day, the estimated average requirement for nonpregnant
      women. Only 1% and 7% of the women consumed 75% and 50%, respectively, of the
      recommended daily folate intake of 400 MUg for nonpregnant women. Over 80% of
      total folate consumption came from cereals, vegetables, and tubers, whereas fruit
      consumption was severely lacking. Underweight women, farmers, women enrolled
      during the winter, and women with access to fewer food types or daily meals were
      more likely to exhibit low folate intake levels. CONCLUSION: Dietary folate
      intake among study participants was far below the recommended intake level. Folic
      acid fortification of cereals is advised to raise folate intake in rural Chinese
      women planning to become pregnant.

PMID- 25066483
TI  - Acute fatal coronary artery dissection following exercise-related blunt chest
      trauma.
AB  - Coronary artery injury such as acute coronary dissection is an uncommon and
      potentially life-threatening complication after blunt chest trauma. The authors
      report an unusual autopsy case of a 43-year-old healthy man who suddenly
      collapsed after receiving a punch to the chest during the practice of kung fu.
      The occurrence of the punch was supported by the presence of one recent contusion
      on the left lateral chest area at the external examination and by areas of
      hemorrhage next to the left lateral intercostal spaces at the internal
      examination. The histological examination revealed the presence of an acute
      dissection of the proximal segment of the left anterior descending coronary
      artery. Only few cases of coronary artery dissection have been reported due to
      trauma during sports activities such as rugby and soccer games, but never during
      the practice of martial arts, sports usually considered as safe and responsible
      for only minor trauma. 

PMID- 25066484
TI  - Roles of testosterone and amygdaloid LTP induction in determining sex differences
      in fear memory magnitude.
AB  - Women are thought to form fear memory more robust than men do and testosterone is
      suspected to play a role in determining such a sex difference. Mouse cued fear
      freezing was used to study the sex-related susceptibility and the role of
      testosterone in fear memory in humans. A 75-dB tone was found to provoke weak
      freezing, while 0.15-mA and 0.20-mA footshock caused strong freezing responses.
      No sex differences were noticed in the tone- or footshock-induced (naive fear)
      freezing. Following the conditionings, female mice exhibited greater tone (cued
      fear)-induced freezing than did male mice. Nonetheless, female mice demonstrated
      indistinctive cued fear freezing across the estrous phases and ovariectomy did
      not affect such freezing in female mice. Orchidectomy enhanced the cued fear
      freezing in male mice. Systemic testosterone administrations and an intra-lateral
      nucleus of amygdala (LA) testosterone infusion diminished the cued fear freezing
      in orchidectomized male mice, while pretreatment with flutamide (Flu) eradicated
      these effects. Long-term potentiation (LTP) magnitude in LA has been known to
      correlate with the strength of the cued fear conditioning. We found that LA LTP
      magnitude was indeed greater in female than male mice. Orchidectomy enhanced LTP
      magnitude in males' LA, while ovariectomy decreased LTP magnitude in females' LA.
      Testosterone decreased LTP magnitude in orchidectomized males' LA and estradiol
      enhanced LTP magnitude in ovariectomized females' LA. Finally, male mice had
      lower LA GluR1 expression than female mice and orchidectomy enhanced the GluR1
      expression in male mice. These findings, taken together, suggest that
      testosterone plays a critical role in rendering the sex differences in the cued
      fear freezing and LA LTP. Testosterone is negatively associated with LA LTP and
      the cued fear memory in male mice. However, ovarian hormones and LA LTP are
      loosely associated with the cued fear memory in female mice. 

PMID- 25066485
TI  - Temperament moderates the influence of periadolescent social experience on
      behavior and adrenocortical activity in adult male rats.
AB  - Adolescence is a period of significant behavioral and physiological maturation,
      particularly related to stress responses. Animal studies that have tested the
      influence of adolescent social experiences on stress-related behavioral and
      physiological development have led to complex results. We used a rodent model of
      neophobia to test the hypothesis that the influence of adolescent social
      experience on adult behavior and adrenocortical function is modulated by pre
      adolescent temperament. Exploratory activity was assessed in 53 male Sprague
      Dawley rats to classify temperament and then they were housed in one of the three
      conditions during postnatal days (PND) 28-46: (1) with familiar kin, (2) with
      novel social partners, or (3) individually with no social partners. Effects on
      adult adrenocortical function were evaluated from fecal samples collected while
      rats were individually-housed and exposed to a 1-hour novel social challenge
      during PND 110-114. Adolescent-housing with novel or no social partners led to
      reduced adult glucocorticoid production compared to adolescent-housing with
      familiar littermates. Additionally, highly-exploratory pre-weanling rats that
      were housed with novel social partners during adolescence exhibited increased
      exploratory behavior and a more rapid return to basal glucocorticoid production
      in adulthood compared to those housed with familiar or no social partners during
      adolescence and compared to low-exploratory rats exposed to novel social
      partners. In sum, relatively short-term adolescent social experiences can cause
      transient changes in temperament and potentially longer-term changes in recovery
      of glucocorticoid production in response to adult social challenges. Furthermore,
      early temperament may modulate the influence of adolescent experiences on adult
      behavioral and adrenocortical function. 

PMID- 25066486
TI  - Role of protease-activated receptors for the innate immune response of the heart.
AB  - Protease-activated receptors (PARs) are a family of G-protein-coupled receptors
      with a unique activation mechanism via cleavage by the serine proteases of the
      coagulation cascade, immune cell-released proteases, and proteases from
      pathogens. Pathogens, such as viruses and bacteria, cause myocarditis and heart
      failure and PAR1 was shown to positively regulate the anti-viral innate immune
      response via interferon beta during virus-induced myocarditis. In contrast, PAR2
      negatively regulated the innate immune response and inhibited the interferon beta
      expression. Thus, PARs play a central role for the innate immune response in the
      heart. 

PMID- 25066488
TI  - Mechanical closure devices for atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most commonly sustained arrhythmia and is a major
      cause of stroke and systemic embolism. Chronic oral anticoagulation reduces this
      risk, but at the cost of increased bleeding. In addition, a substantial
      proportion of AF patients who are at moderate-to-high risk for stroke are
      undertreated due to real or perceived contraindications. The major source of
      thromboembolism in AF appears to be the left atrial appendage (LAA). Therefore,
      device closure of the LAA represents a mechanical approach to stroke prevention
      in AF patients. In this review, we describe the rationale for device closure of
      the LAA, summarize the current dataset for LAA closure devices, and set forth a
      framework to help guide patient selection for device therapy. 

PMID- 25066489
TI  - The value of cardiac genetic testing.
AB  - Genetic testing is an important and necessary aspect of the management of
      families with cardiac genetic conditions. Commercial genetic tests are available
      for most cardiac genetic diseases, and increasing uptake amongst patients has
      contributed to a vastly improved knowledge of the genetic basis of these
      diseases. The incredible advances in genetic technologies have translated to
      faster, more comprehensive, and inexpensive commercial genetic tests and has
      completely changed the landscape of commercial genetic testing in recent years.
      While there are enormous challenges, mostly relating to interpretation of
      variants, the value of a genetic diagnosis should not be underestimated. In
      almost all cases, the single greatest utility is for the predictive genetic
      testing of family members. This review will describe the value of cardiac genetic
      testing in the current climate of rapid genetic advancements. 

PMID- 25066487
TI  - An emerging role for the miR-26 family in cardiovascular disease.
AB  - In response to acute myocardial infarction (MI), a complex series of cellular and
      molecular signaling events orchestrate the myocardial remodeling that ensues
      weeks to months after injury. Clinical, epidemiological, and pathological studies
      demonstrate that inadequate or impaired angiogenesis after myocardial injury is
      often associated with decreased left ventricular (LV) function and clinical
      outcomes. The microRNA family, miR-26, plays diverse roles in regulating key
      aspects of cellular growth, development, and activation. Recent evidence supports
      a central role for the miR-26 family in cardiovascular disease by controlling
      critical signaling pathways, such as BMP/SMAD1 signaling, and targets relevant to
      endothelial cell growth, angiogenesis, and LV function post-MI. Emerging studies
      of the miR-26 family in other cell types including vascular smooth muscle cells,
      cardiac fibroblasts, and cardiomyocytes suggest that miR-26 may bear important
      implications for a range of cardiovascular repair mechanisms. This review
      examines the current knowledge of the miR-26 family's role in key cell types that
      critically control cardiovascular disease under pathological and physiological
      stimuli. 

PMID- 25066490
TI  - The role of stereotactic body radiotherapy and stereotactic radiosurgery in the
      re-irradiation of metastatic spinal tumors.
AB  - Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) are
      advanced radiotherapy delivery techniques that allow for the delivery of high
      dose per fraction radiation. Advances in imaging technology and intensity
      modulation have allowed SRS and SBRT to be used for the treatment of tumors in
      close proximity to the spinal cord and cauda equina, in particular spinal
      metastases. While the initial treatment of spinal metastases is often
      conventional palliative radiotherapy, treatment failure is not uncommon, and
      conventional re-irradiation may not be feasible due to spinal cord tolerance.
      SBRT and SRS have emerged as important techniques for the treatment of spinal
      metastases in the proximity of previously irradiated spinal cord. Here we review
      the current data on the use of SBRT and SRS spinal re-irradiation, and future
      directions for these important treatment modalities. 

PMID- 25066491
TI  - Abnormal resting-state connectivity of motor and cognitive networks in early
      manifest Huntington's disease.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) of multiple neural
      networks during the brain's 'resting state' could facilitate biomarker
      development in patients with Huntington's disease (HD) and may provide new
      insights into the relationship between neural dysfunction and clinical symptoms.
      To date, however, very few studies have examined the functional integrity of
      multiple resting state networks (RSNs) in manifest HD, and even less is known
      about whether concomitant brain atrophy affects neural activity in patients.
      METHOD: Using MRI, we investigated brain structure and RSN function in patients
      with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data
      a group-independent component analysis identified spatiotemporally distinct
      patterns of motor and prefrontal RSNs of interest. We used voxel-based
      morphometry to assess regional brain atrophy, and 'biological parametric mapping'
      analyses to investigate the impact of atrophy on neural activity. RESULTS:
      Compared with controls, patients showed connectivity changes within distinct
      neural systems including lateral prefrontal, supplementary motor, thalamic,
      cingulate, temporal and parietal regions. In patients, supplementary motor area
      and cingulate cortex connectivity indices were associated with measures of motor
      function, whereas lateral prefrontal connectivity was associated with cognition.
      CONCLUSIONS: This study provides evidence for aberrant connectivity of RSNs
      associated with motor function and cognition in early manifest HD when
      controlling for brain atrophy. This suggests clinically relevant changes of RSN
      activity in the presence of HD-associated cortical and subcortical structural
      abnormalities.

PMID- 25066493
TI  - Molecular dynamics of the structural changes of helical peptides induced by
      pressure.
AB  - An AK16 peptide and a C-peptide analog are experimentally known to form more
      helical structures under high-pressure conditions than those at atmospheric
      pressure, even though most proteins usually unfold at high pressure. To
      understand the pressure-induced structural changes of the two peptides, molecular
      dynamics simulations with the simulated tempering method for the isobaric
      isothermal ensemble were performed in a wide pressure range from 0.1 MPa to 1.4
      GPa. We found that the fraction of the folded state decreases once and then
      increases with increasing pressure for both peptides. The partial molar volume
      change of both peptides from the folded state to the unfolded state increases
      monotonically from a negative value to a positive value as pressure increases. By
      calculating the radius of gyration and interatomic distances of the AK16 peptide
      and the C-peptide analog, we found that these peptides are compressed under high
      pressure conditions, which causes the folded state to be more stable at high
      pressure. Furthermore, we found that the salt bridge of the C-peptide analog is
      broken under high pressure.

PMID- 25066494
TI  - Toxoplasma gondii isolates from mouflon sheep (Ovis ammon) from Hawaii, USA.
AB  - Little is known of Toxoplasma gondii isolates circulating in wildlife. The
      mouflon (Ovis ammon) is very popular game animal, hunted for its trophy horns.
      Here, we report the isolation and genetic characterization of T. gondii from two
      mouflons from Hawaii, USA. Both sheep had antibodies titers of 1:800 or higher.
      Viable T. gondii were isolated and nested PCR-RFLP genotyping revealed two
      genotypes, a clonal Type III (designated TgMouflonUS1), and a new genotype
      (designated TgMouflonUS2, and ToxoDB PCR-RFLP genotypes #249). This is the first
      report of T. gondii infection, isolation and genetic characterization in mouflons
      from the USA. 

PMID- 25066492
TI  - Use of healthcare resources and costs of acute cardioembolic stroke management in
      the Region of Madrid: The CODICE Study.
AB  - INTRODUCTION: Stroke is the main cause of admission to Neurology departments and
      cardioembolic stroke (CS) is one of the most common subtypes of stroke. METHODS:
      A multicentre prospective observational study was performed in 5 Neurology
      departments in public hospitals in the Region of Madrid (Spain). The objective
      was to estimate the use of healthcare resources and costs of acute CS management.
      Patients with acute CS at<48h from onset were recruited. Patients' socio
      demographic, clinical, and healthcare resource use data were collected during
      hospitalisation and at discharge up to 30 days after admission, including data
      for rehabilitation treatment after discharge. RESULTS: During an 8-month
      recruitment period, 128 patients were recruited: mean age, 75.3+/-11.25; 46.9%
      women; mortality rate, 4.7%. All patients met the CS diagnostic criteria
      established by GEENCV-SEN, based on medical history or diagnostic tests. Fifty
      per cent of the patients had a history of atrial fibrillation and 18.8% presented
      other major cardioembolic sources. Non-valvular atrial fibrillation was the most
      frequent cause of CS (33.6%). Data for healthcare resource use, given a mean
      total hospital stay of 10.3+/-9.3 days, are as follows: rehabilitation therapy
      during hospital stay (46.9%, mean 4.5 days) and after discharge (56.3%, mean 26.8
      days), complications (32%), specific interventions (19.5%), and laboratory and
      diagnostic tests (100%). Head CT (98.4%), duplex ultrasound of supra-aortic
      trunks (87.5%), and electrocardiogram (85.9%) were the most frequently performed
      diagnostic procedures. Average total cost per patient during acute-phase
      management and rehabilitation was ?13,139. Hospital stay (45.0%) and
      rehabilitation at discharge (29.2%) accounted for the largest part of resources
      used. CONCLUSIONS: Acute CS management in the Region of Madrid resulted consumes
      large amounts of resources (?13,139), mainly due to hospital stays and
      rehabilitation.

PMID- 25066495
TI  - Relationship between membrane fatty acids and cognitive symptoms and information
      processing in individuals at ultra-high risk for psychosis.
AB  - Cognitive symptoms and impairment are central to schizophrenia and often an early
      sign of this condition. The present study investigated biological correlates of
      cognitive symptoms and performance in individuals at ultra-high risk (UHR) for
      psychosis. The study sample comprised 80 neuroleptic-naive UHR individuals aged
      13-25 years. Associations among erythrocyte membrane fatty acid levels, measured
      by gas chromatography, and cognitive functioning were investigated in UHR
      patients. Subjects were divided into terciles based on their scores on the
      cognitive factor of the Positive and Negative Syndrome Scale. The Zahlen
      Verbindungs Test (ZVT) (the number-combination test) was also used as a measure
      of information-processing speed. Exploratory analysis was conducted to
      investigate the relationship between membrane fatty acid levels with the size of
      the intracranial area (ICA), a neurodevelopmental measure relevant to
      schizophrenia, in half of subjects (n=40) using magnetic resonance imaging. The
      adjusted analysis revealed that omega-9 eicosenoic and erucic acid levels were
      significantly higher, but omega-3 docosahexaenoic acid levels were significantly
      lower, in the cognitively impaired than in the cognitively intact group. We found
      a significant negative association of eicosenoic, erucic, and gamma-linoleic
      acids with ZVT scores. A negative association between ICA and membrane levels of
      eicosenoic acid was also found. This is the first study to demonstrate the
      relationship between membrane fatty acids and cognitive function in neuroleptic
      naive subjects at UHR for psychosis. The study findings indicate that
      abnormalities in membrane fatty acids may be associated with the
      neurodevelopmental disruption associated with the cognitive impairments of
      individuals at UHR for psychosis.

PMID- 25066496
TI  - White matter microstructural abnormalities of the cingulum bundle in youths with
      22q11.2 deletion syndrome: associations with medication, neuropsychological
      function, and prodromal symptoms of psychosis.
AB  - BACKGROUND: The 22q11.2 deletion syndrome (22q11.2DS) is regarded as an
      etiologically homogenous model for understanding neuroanatomic disruptions
      associated with a high risk for schizophrenia. This study utilized diffusion
      tensor imaging (DTI) to analyze white matter microstructure in individuals with
      22q11.2DS. We focused on the cingulum bundle (CB), previously shown to be
      disrupted in patients with schizophrenia and associated with symptoms of
      psychosis. METHODS: White matter microstructure was assessed in the anterior,
      superior, and posterior CB using the tractography algorithm in DTIStudio.
      Neuropsychological function, presence of prodromal symptoms of psychosis, and
      medication history were assessed in all participants. RESULTS: Relative to
      controls, young adults with 22q11.2DS showed alterations in most DTI metrics of
      the CB. Alterations were associated with positive prodromal symptoms of
      psychosis. However, when individuals with 22q11.2DS were divided by usage of
      antipsychotics/mood stabilizers, the medicated and non-medicated groups differed
      significantly in axial diffusivity of the anterior CB and in fractional
      anisotropy of the superior CB. DTI metrics did not differ between the medicated
      group and the control group. CONCLUSIONS: Results suggest that the microstructure
      of the CB is altered in individuals with 22q11.2DS, and that those alterations
      may underlie positive prodromal symptoms of psychosis. Our findings further
      provide preliminary evidence that antipsychotic/mood stabilizer usage may have a
      reparative effect on white matter microstructure in prodromal 22q11.2DS,
      independent of the potential effects of psychosis. Future studies of white matter
      pathology in individuals with 22q11.2DS should test for potential effects of
      medication on white matter microstructure.

PMID- 25066498
TI  - Substantive review of the literature of medication treatment of chronic low back
      pain among adults.
AB  - PURPOSE: Pain can be debilitating, and it is often inadequately treated,
      particularly among patients with chronic low back pain (CLBP). CLBP has a
      substantial economic impact, as it affects an individual's ability to perform
      activities of daily living and maintain employment. This study aims to review
      original studies related to the evidence-based management of patients with CLBP
      to develop an algorithm for prescribing medications and recommending other
      treatment modalities for patients with CLBP. DATA SOURCES: An electronic search
      of PubMed, CINAHL, and the Cochrane Database was conducted to identify studies
      related to the evidence-based management of CLBP that were performed between 2003
      and 2012. The following keywords were used: low back pain, back pain, chronic
      back pain, medication management, and adjunct therapy. The selected articles were
      specific to CLBP, medication-based management, and additional treatment options,
      such as adjunct therapies. CONCLUSIONS: The collected data revealed that there
      are a number of approaches to the management of CLBP. Medication regimens are
      frequently used and widely available, but alternative treatment modalities can
      also be effective. IMPLICATIONS FOR PRACTICE: Providers should encourage patients
      to explore a variety of treatment modalities that can provide pain relief and
      improve functionality and overall well-being.

PMID- 25066497
TI  - A comparison of neuropsychological performance between US and Russia: preparing
      for a global clinical trial.
AB  - BACKGROUND: Understanding regional differences in cognitive performance is
      important for interpretation of data from large multinational clinical trials.
      METHODS: Data from Durham and Cabarrus Counties in North Carolina, USA and Tomsk,
      Russia (n = 2972) were evaluated. The Montreal Cognitive Assessment (MoCA), Trail
      Making Test Part B (Trails B), Consortium to Establish a Registry for Alzheimer's
      Disease Word List Memory Test (WLM) delayed recall, and self-report Alzheimer's
      Disease Cooperative Studies Mail-In Cognitive Function Screening Instrument
      (MCFSI) were administered at each site. Multilevel modeling measured the variance
      explained by site and predictors of cognitive performance. RESULTS: Site
      differences accounted for 11% of the variation in the MoCA, 1.6% in Trails B,
      1.7% in WLM, and 0.8% in MCFSI scores. Prior memory testing was significantly
      associated with WLM. Diabetes and stroke were significantly associated with
      Trails B and MCFSI. CONCLUSIONS: Sources of variation include cultural
      differences, health conditions, and exposure to test stimuli. Findings highlight
      the importance of local norms to interpret test performance.

PMID- 25066499
TI  - [Acute marijuana milk poisoning].

PMID- 25066500
TI  - [Genetic and environmental contributions to body mass index in a Spanish
      adolescent twin sample].
AB  - BACKGROUND AND OBJECTIVE: Twin and family studies support large genetic
      influences on variability in body mass index (BMI), with heritability estimates
      ranging from 47% to over 90%. Our objective was to study the relative
      contributions of genetics and environment to BMI, evaluating sex differences, in
      an adolescent twin sample from Valencia, Spain. MATERIAL AND METHODS: Five
      hundred eighty-four pairs of adolescent twins between 13 and 18 years of age
      completed the study (82 monozygotic [MZ] and 87 dizygotic [DZ] pairs of male
      twins, 118 MZ and 102 DZ pairs of female twins, and 195 opposite-sex pairs of DZ
      twins). To determine zygosity, teachers responded a questionnaire on physical
      similarity. They also measured the participant's height and weight. BMI was
      calculated and weight status was determined according to age. We used twin models
      to assess genetic and environmental (common and unique) factors affecting BMI.
      RESULTS: There was a 7.1% frequency of overweight and 2.8% of obesity. The
      estimated heritability of BMI was 88.0% in boys and 72.1% in girls, with the
      remaining variance attributable to non-shared environment in boys (12.0%) and
      8.8% in girls. It was only in girls that common environment had an effect on BMI.
      CONCLUSIONS: Genetics appears to play an important role in explaining the
      variability in BMI in the adolescence, with slight variations between boys and
      girls. Common environmental factors exert their influence on BMI only in girls.

PMID- 25066501
TI  - [Clinical management: patients, professionals, managers and politicians with the
      challenge of each one comprehensively taking the place of the other].

PMID- 25066502
TI  - The Effect of Decortication for Periosteal Expansion Osteogenesis Using Shape
      Memory Alloy Mesh Device.
AB  - BACKGROUND: In conventional bone grafting technique, decortication procedure
      enhances the healing process and bone regeneration to reach the grafted site more
      readily. PURPOSE: This study evaluates to improve periosteal expansion
      osteogenesis (PEO) using a shape memory alloy mesh (SMA) device with
      decortication in a rabbit model. MATERIALS AND METHODS: The SMA device was
      inserted under the periosteum at the forehead and pushed, bent, and attached to
      the bone surface and fixed with a titanium screw. Twelve rabbits were divided
      into two groups: PEO without decortication (P group) and with decortication (D
      group). After 2 weeks, the screw was removed, and the mesh was activated by its
      own elasticity. Rabbits were sacrificed 5 (P1/D1) and 8 (P2/D2) weeks after
      operation and histologically and radiographically evaluated. RESULTS: The mean
      activation height was 2.9 +/- 0.5 mm. The ratio of new bone volume in the
      elevated volume was 17.6% in P1, 59.8% in D1 33.4% in P2, and 65.1% in D2. D
      group had a statistically higher volume of new bone than P group during each
      period (p < .05). CONCLUSION: PEO with decortication appears to be a promising
      clinical alternative for bone augmentation and introduces the new concept of
      "dynamic graft and guided bone regeneration (GBR)."

PMID- 25066503
TI  - Cervical kinematic training with and without interactive VR training for chronic
      neck pain - a randomized clinical trial.
AB  - Impairments in cervical kinematics are common in patients with neck pain. A
      virtual reality (VR) device has potential to be effective in the management of
      these impairments. The objective of this study was to investigate the effect of
      kinematic training (KT) with and without the use of an interactive VR device. In
      this assessor-blinded, allocation-concealed pilot clinical trial, 32 participants
      with chronic neck pain were randomised into the KT or kinematic plus VR training
      (KTVR) group. Both groups completed four to six training sessions comprising of
      similar KT activities such as active and quick head movements and fine head
      movement control and stability over five weeks. Only the KTVR group used the VR
      device. The primary outcome measures were neck disability index (NDI), cervical
      range of motion (ROM), head movement velocity and accuracy. Kinematic measures
      were collected using the VR system that was also used for training. Secondary
      measures included pain intensity, TAMPA scale of kinesiophobia, static and
      dynamic balance, global perceived effect and participant satisfaction. The
      results demonstrated significant (p < 0.05) improvements in NDI, ROM (rotation),
      velocity, and the step test in both groups post-intervention. At 3-month post
      intervention, these improvements were mostly sustained; however there was no
      control group, which limits the interpretation of this. Between-group analysis
      showed a few specific differences including global perceived change that was
      greater in the KTVR group. This pilot study has provided directions and
      justification for future research exploring training using kinematic training and
      VR for those with neck pain in a larger cohort.

PMID- 25066504
TI  - Measurement of renal cortical thickness using noncontrast-enhanced steady-state
      free precession MRI with spatially selective inversion recovery pulse:
      Association with renal function.
AB  - PURPOSE: To assess whether noncontrast-enhanced steady-state free precession
      (SSFP) magnetic resonance imaging (MRI) with a spatially selective inversion
      recovery (IR) pulse can improve the visibility of renal corticomedullary
      differentiation in patients showing renal dysfunction, and to investigate the
      correlation between renal cortical thickness and estimated glomerular filtration
      rate (eGFR). MATERIALS AND METHODS: Sixty-five patients with and without chronic
      kidney diseases (CKD) were investigated. Based on eGFR, patients were divided
      into three groups (Group 1, eGFR < 60; Group 2, eGFR = 60-90; and Group 3, eGFR >
      90). All patients underwent noncontrast-enhanced SSFP MRI with spatially
      selective IR pulses and minimal renal cortical thickness was measured. RESULTS:
      The mean corticomedullary contrast ratio was significantly higher in SSFP images
      with optimal TI than in in-phase images in all three groups (P = 0.001). Positive
      correlation was seen between the corticomedullary contrast ratio in SSFP images
      with optimal TI and eGFR (P = 0.011, r = 0.314). A significantly positive
      correlation was observed between minimal renal cortical thickness and eGFR (P <
      0.01, r = 0.495). CONCLUSION: Noncontrast-enhanced SSFP MRI with a spatially
      selective IR pulse using optimal TI can improve the visibility of renal
      corticomedullary differentiation even in patients with renal insufficiency. The
      decrease in renal cortical thickness measured using this technique correlated
      significantly with eGFR.

PMID- 25066505
TI  - Reduced prevalence of placental malaria in primiparae with blood group O.
AB  - BACKGROUND: Blood group O protects African children against severe malaria and
      has reached high prevalence in malarious regions. However, its role in malaria in
      pregnancy is ambiguous. In 839 delivering Ghanaian women, associations of ABO
      blood groups with Plasmodium falciparum infection were examined. METHODS:
      Plasmodium falciparum infection was diagnosed in placental blood samples by
      microscopy and PCR assays. Present or past infection was defined as the detection
      of parasitaemia or haemozoin by microscopy, or a positive PCR result. Blood
      groups were inferred from genotyping rs8176719 (indicating the O allele) and
      rs8176746/rs8176747 (distinguishing the B allele from the A allele). RESULTS: The
      majority of women had blood group O (55.4%); present or past P. falciparum
      infection was seen in 62.3% of all women. Among multiparae, the blood groups had
      no influence on P. falciparum infection. In contrast, primiparae with blood group
      O had significantly less present or past infection than women with non-O blood
      groups (61.5 vs 76.2%, P = 0.007). In multivariate analysis, the odds of present
      or past placental P. falciparum infection were reduced by 45% in blood group O
      primiparae (aOR, 0.55 [95% CI, 0.33-0.94]). CONCLUSIONS: The present study shows
      a clear protective effect of blood group O against malaria in primiparae. This
      accords with findings in severe malaria and in vitro results. The data underline
      the relevance of host genetic protection among primiparae, i.e. the high-risk
      group for malaria in pregnancy, and contribute to the understanding of high O
      allele frequencies in Africa.

PMID- 25066506
TI  - [Practice guideline for diagnosis and treatment of craniopharyngioma and
      parasellar tumors of the pituitary gland].
AB  - Craniopharyngiomas are rare, locally aggressive epithelial tumors usually located
      in the sellar and suprasellar region. Diagnosis of craniopharyngioma is usually
      suggested by clinical and radiological findings that should be confirmed
      histologically. Surgery is the treatment of choice for most patients. The goal of
      surgery is to relieve compressive symptoms and to remove as much tumor as safely
      possible. Radiation therapy is the usual treatment to control postoperative tumor
      remnants and local recurrences. Parasellar lesions are low prevalent lesions and
      include neoplastic, inflammatory, infectious, developmental, and vascular
      diseases. Both their diagnosis and treatment depend on the type of lesion. 

PMID- 25066507
TI  - Comprehensive BRCA1 and BRCA2 mutational profile in Lithuania.
AB  - There is limited knowledge about the BRCA1/2 mutational profile in Lithuania. We
      aimed to define the full BRCA1 and BRCA2 mutational spectrum and the clinically
      relevant prevalence of these gene mutations in Lithuania. A data set of 753
      unrelated probands, recruited through a clinical setting, was used and consisted
      of 380 female breast cancer cases, 213 epithelial ovarian cancer cases, 20 breast
      and ovarian cancer cases, and 140 probands with positive family history of breast
      or ovarian cancer. A comprehensive mutation analysis of the BRCA1/2 genes by high
      resolution melting analysis coupled with Sanger sequencing and multiplex ligation
      dependent probe amplification analysis was performed. Genetic analysis revealed
      32 different pathogenic germline BRCA1/2 mutations: 20 in the BRCA1 gene and 12
      in the BRCA2 gene, including four different large genomic rearrangements in the
      BRCA1 gene. In all, 10 novel BRCA1/2 mutations were found. Nine different
      recurrent BRCA1 mutations and two recurrent BRCA2 mutations were identified,
      which comprised 90.4% of all BRCA1/2 mutations. BRCA1 exon 1-3 deletion and BRCA2
      c.658_659del are reported for the first time as recurrent mutations, pointing to
      a possible Baltic founder effect. Approximately 7% of breast cancer and 22% of
      ovarian cancer patients without family history and an estimated 0.5-0.6% of all
      Lithuanian women were found to be carriers of mutations in the BRCA1 or BRCA2
      gene. 

PMID- 25066508
TI  - Ruthenium porphyrins with axial pi-conjugated arylamide and arylimide ligands.
AB  - A series of ruthenium porphyrins [Ru(IV)(por)(NHY)2] and [Ru(VI)(por)(NY)2]
      bearing axially coordinated pi-conjugated arylamide and arylimide ligands,
      respectively, have been synthesized. The crystal structures of
      [Ru(IV)(tmp)(NHY)2] (tmp = 5,10,15,20-tetramesitylporphyrinato(2-)) with Y = 4'
      methoxy-biphenyl-4-yl (Ar-Ar-p-OMe), 4'-chloro-biphenyl-4-yl (Ar-Ar-p-Cl), and
      9,9-dibutyl-fluoren-2-yl (Ar^Ar) show axial Ru-N(arylamide) distances of
      1.978(4), 1.971(6), and 1.985(13) A, respectively. [Ru(IV)(tmp)(NH{Ar^Ar})2] is
      an example of metalloporphyrins that bind an arylamide ligand featuring a co
      planar biphenyl unit. The [Ru(IV)(por)(NHY)2] complexes show a quasi-reversible
      reduction couple or irreversible reduction wave attributed to Ru(IV)->Ru(III)
      with Epc from -1.06 to -1.40 V versus Cp2Fe(+/0) and an irreversible oxidation
      wave with Epa from -0.04 to 0.19 V versus Cp2Fe(+/0). Reaction of the
      [Ru(IV)(por)(NHY)2] with bromine afforded [Ru(IV)(por)(NHY)Br]. PhI(OAc)2
      oxidation of the [Ru(IV)(por)(NHY)2] gave [Ru(VI)(por)(NY)2]; the latter can be
      prepared from reaction of [Ru(II)(por)(CO)] with aryl azides N3Y. The crystal
      structure of [Ru(VI)(tmp)(N{Ar-Ar-p-OMe})2] features Ru-N(arylimide) distances of
      1.824(5) and 1.829(5) A. Alkene aziridination and C-H amination catalyzed by
      "[Ru(II)(tmp)(CO)]+pi-conjugated aryl azides", or mediated by [Ru(VI)(por)(NY)2]
      with Y = biphenyl-4-yl (Ar-Ar) and Ar-Ar-p-Cl, gave aziridines and amines in
      moderate yields. The electronic structure of [Ru(VI)(por)(NY)2] was examined by
      DFT calculations.

PMID- 25066509
TI  - Crack pipe sharing among street-involved youth in a Canadian setting.
AB  - INTRODUCTION AND AIMS: Crack pipe sharing is a risky practice that has been
      associated with the transmission of hepatitis C and other harms. While previous
      research has exclusively focused on this phenomenon among adults, this study
      examines crack pipe sharing among street-involved youth. DESIGN AND METHODS: From
      May 2006 to May 2012, data were collected from the At-Risk Youth Study, a cohort
      of street-involved youth aged 14-26 in Vancouver, Canada. Survey data from active
      crack smokers were analysed using generalised estimating equations logistic
      regression. RESULTS: Over the study period, 567 youth reported smoking crack
      cocaine and contributed 1288 observations, among which 961 (75%) included a
      report of crack pipe sharing. In multivariate analysis, factors that were
      associated with crack pipe sharing included difficulty accessing crack pipes
      [adjusted odds ratio (AOR) = 1.58, 95% confidence interval (CI) 1.13-2.20];
      homelessness (AOR = 1.87, 95% CI 1.43-2.44); regular employment (AOR = 1.53, 95%
      CI 1.15-2.04); daily non-injection crystal methamphetamine use (AOR = 2.04, 95%
      CI 1.11-3.75); daily crack smoking (AOR = 1.37, 95% CI 1.01-1.85); encounters
      with the police (AOR = 1.42, 95% CI 1.01-1.99); and reporting unprotected sex
      (AOR = 1.95, 95% CI 1.47-2.58). DISCUSSION AND CONCLUSIONS: The prevalence of
      crack pipe sharing was high among our sample and independently associated with
      structural factors including difficulty accessing crack pipes and homelessness.
      Crack pipe sharing was also associated with high-intensity drug use and a number
      of other markers of risk and vulnerability. Collectively, these findings
      highlight opportunities for health services to better engage with this vulnerable
      group and reduce this risky behaviour.

PMID- 25066510
TI  - The descriptive epidemiology of delirium symptoms in a large population-based
      cohort study: results from the Medical Research Council Cognitive Function and
      Ageing Study (MRC CFAS).
AB  - BACKGROUND: In the general population, the epidemiological relationships between
      delirium and adverse outcomes are not well defined. The aims of this study were
      to: (1) construct an algorithm for the diagnosis of delirium using the Geriatric
      Mental State (GMS) examination; (2) test the criterion validity of this algorithm
      against mortality and dementia risk; (3) report the age-specific prevalence of
      delirium as determined by this algorithm. METHODS: Participant and informant data
      in a randomly weighted subsample of the Cognitive Function and Ageing Study were
      taken from a standardized assessment battery. The algorithmic definition of
      delirium was based on the DSM-IV classification. Outcomes were: proportional
      hazard ratios for death; odds ratios of dementia at 2-year follow-up. RESULTS:
      Data from 2197 persons (representative of 13,004) were used, median age 77 years,
      64% women. Study-defined delirium was associated with a new dementia diagnosis at
      two years (OR 8.82, 95% CI 2.76 to 28.2) and death (HR 1.28, 95% CI 1.03 to
      1.60), even after adjustment for acute illness severity. Similar associations
      were seen for study-defined subsyndromal delirium. Age-specific prevalence as
      determined by the algorithm increased with age from 1.8% in the 65-69 year age
      group to 10.1% in the >=85 age group (p < 0.01 for trend). For study-defined
      subsyndromal delirium, age-specific period prevalence ranged from 8.2% (65-69
      years) to 36.1% (>=85 years). CONCLUSIONS: These results demonstrate the
      possibility of constructing an algorithmic diagnosis for study-defined delirium
      using data from the GMS schedule, with predictive criterion validity for
      mortality and dementia risk. These are the first population-based analyses able
      to account prospectively for both illness severity and an earlier study diagnosis
      of dementia.

PMID- 25066512
TI  - How traits shape trees: new approaches for detecting character state-dependent
      lineage diversification.
AB  - Biologists have long sought to understand the processes underlying disparities in
      clade size across the tree of life and the extent to which such clade size
      differences can be attributed to the evolution of particular traits. The
      association of certain character states with species-rich clades suggests that
      trait evolution can lead to increased diversification, but such a pattern could
      also arise due other processes, such as directional trait evolution. Recent
      advances in phylogenetic comparative methods have provided new statistical
      approaches for distinguishing between these intertwined and potentially
      confounded macroevolutionary processes. Here, we review the historical
      development of methods for detecting state-dependent diversification and explore
      what new methods have revealed about classic examples of traits that affect
      diversification, including evolutionary dead ends, key innovations and geographic
      traits. Applications of these methods thus far collectively suggest that trait
      diversity commonly arises through the complex interplay between transition,
      speciation and extinction rates and that long hypothesized evolutionary dead ends
      and key innovations are instead often cases of directional trends in trait
      evolution. 

PMID- 25066511
TI  - Bacillus subtilis spores expressing the VP28 antigen: a potential oral treatment
      to protect Litopenaeus vannamei against white spot syndrome.
AB  - The envelope protein VP28 of white spot syndrome virus (WSSV) is considered a
      candidate antigen for use in a potential vaccine to this important shrimp
      pathogen (the cause of white spot syndrome, WSS). Here, we used spores of
      Bacillus subtilis to display VP28 on the spore surface. Trials were conducted to
      evaluate their ability to protect shrimps against WSSV infection. The gene cotB
      vp28 was integrated into the chromosome of the laboratory strain B. subtilis
      PY79, and expression of CotB-VP28 was detected by Western blotting and
      immunofluorescence. Expression of CotB-VP28 was equivalent to 1000 molecules per
      spore. PY79 and CotB-VP28 spores were mixed with pellets for feeding of whiteleg
      shrimps (Litopenaeus vannamei), followed by WSSV challenge. Superoxidase
      dismutase (SOD), phenoloxidase activities and mortality rates of the two shrimp
      groups were evaluated. Groups fed with PY79 and CotB-VP28 spores at day 7 had
      increased SOD activities of 29% and increased phenoloxidase activities of 15% and
      33%, respectively, compared to those of the control group. Fourteen days
      postchallenge, 35% of vaccinated shrimps had died compared to 49% of those fed
      naked spores (PY79) and 66% untreated, unchallenged animals. These data suggest
      that spores expressing VP28 have potential as a prophylactic treatment of WSS. 

PMID- 25066513
TI  - Revascularization of an immature tooth with apical periodontitis using a single
      visit protocol: a case report.
AB  - AIM: To discuss the clinical and radiological outcome of a revascularization
      procedure which was completed in a single visit (using sodium hypochlorite 5% as
      the sole disinfectant) in an immature tooth with a necrotic pulp and apical
      periodontitis. SUMMARY: A 7-year-old girl was referred in pain following trauma
      to the maxillary anterior region some 6-7 weeks previously. The maxillary left
      central incisor tooth was diagnosed with a necrotic pulp and acute apical
      periodontitis. Under local anaesthesia and rubber dam isolation, an access cavity
      was prepared. The canal was irrigated with a 5% sodium hypochlorite solution and
      agitated with an ultrasonic file. A 17% EDTA solution was also used for a final
      rinse. Bleeding was induced into the canal space from the periapical tissues
      using a K-file. An MTA layer/barrier was placed directly onto the blood clot, and
      a further layer of GC Fuji IX cement was placed on top of the MTA to restore the
      access cavity. The tooth was reevaluated at 6 weeks, 3 months, 6 months, 1 year
      and 18 months. The tooth has remained symptom free. Radiographic examination
      shows progressive thickening of the root canal walls, root lengthening and apical
      closure. KEY LEARNING POINTS: Disinfection with 5% sodium hypochlorite followed
      by the induction of a blood clot into the root canal space may be sufficient to
      promote revascularization in certain circumstances. A single visit
      revascularization procedure is a potential treatment option.

PMID- 25066514
TI  - The DENALI Trial: an interim analysis of a prospective, multicenter study of the
      Denali retrievable inferior vena cava filter.
AB  - PURPOSE: To assess safety and effectiveness of a nitinol retrievable inferior
      vena cava (IVC) filter in patients who require caval interruption to protect
      against pulmonary embolism (PE). MATERIALS AND METHODS: Two hundred patients with
      temporary indications for an IVC filter were enrolled in this prospective,
      multicenter clinical study. Patients undergoing filter implantation were to be
      followed for 2 years or for 30 days after filter retrieval. At the time of the
      present interim report, all 200 patients had been enrolled in the study, and 160
      had undergone a retrieval attempt or been followed to 6 months with their filter
      in place. Primary study endpoints included technical and clinical success of
      filter placement and retrieval. Patients were also evaluated for recurrent PE,
      new or worsening deep vein thrombosis, and filter migration, fracture,
      penetration, and tilt. RESULTS: Clinical success of placement was achieved in
      94.5% of patients (172 of 182), with a one-sided lower limit of the 95%
      confidence interval of 90.1%. Technical success rate of filter placement was
      99.5%. Technical success rate of retrieval was 97.3%; 108 filters were retrieved
      in 111 attempts. In two cases, the filter apex could not be engaged with a snare,
      and one device was engaged but could not be removed. Filter retrievals occurred
      at a mean indwell time of 165 days (range, 5-632 d). There were no instances of
      filter fracture, migration, or tilt greater than 15 degrees  at the time of
      retrieval or 6-month follow-up. CONCLUSIONS: In this interim report, the nitinol
      retrievable IVC filter provided protection against pulmonary embolism, and the
      device could be retrieved with a low rate of complications.

PMID- 25066515
TI  - Gender difference in metabolic responses to surface electrical muscle stimulation
      in type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to examine whether or not there is a gender
      difference in metabolic responses to surface electrical muscle stimulation (sEMS)
      in type 2 diabetes (T2DM). METHODS: Ten men and eight women with T2DM
      participated in two sessions; in both sessions the subjects were investigated
      after a breakfast and that in one occasion they underwent 30-min sEMS while in
      the other they were followed while resting. Blood and gas exchange data were
      compared between genders as to the extent of blood glucose and non-esterified
      fatty acids responses to sEMS. RESULTS: The time course change of blood glucose
      concentration after sEMS did not statistically differ between genders while sEMS
      could attenuate postprandial blood glucose level regardless of gender (p<0.05).
      Women had a lower respiratory quotient and lactate concentration during sEMS when
      compared with men (p<0.05). CONCLUSIONS: This study indicated that sEMS might
      have resulted in lower anaerobic glycolysis in women as compared to men with
      T2DM. sEMS is expected to be a new exercise method in T2DM. Determining the
      possible gender differences and precise mechanisms might further shed some light
      for the efficacy of sEMS use for clinical practice.

PMID- 25066516
TI  - The effects of surface condition on abdominal muscle activity during single
      legged hold exercise.
AB  - To treat low-back pain, various spinal stability exercises are commonly used to
      improve trunk muscle function and strength. Because human movement for normal
      daily activity occurs in multi-dimensions, the importance of exercise in multi
      dimensions or on unstable surfaces has been emphasized. Recently, a motorized
      rotating platform (MRP) for facilitating multi-dimensions dynamic movement was
      introduced for clinical use. However, the abdominal muscle activity with this
      device has not been reported. The purpose of this study was to compare the
      abdominal muscle activity (rectus abdominis, external and internal oblique
      muscles) during an active single-leg-hold (SLH) exercise on a floor (stable
      surface), foam roll, and motorized rotating platform (MRP). Thirteen healthy male
      subjects participated in this study. Using electromyography, the abdominal muscle
      activity was measured while the subjects performed SLH exercises on floor (stable
      surface), foam roll, and MRP. There were significant differences in the abdominal
      muscle activities among conditions (P<.05), except for left EO (P>.05) (Fig. 2).
      After the Bonferroni correction, however, no significant differences among
      conditions remained, except for differences in both side IO muscle activity
      between the floor and foam roll conditions (padj<0.017). The findings suggest
      that performing the SLH exercises on a foam roll and MRP is more effective
      increased activities of both side of RA and IO, and Rt. EO compared to floor
      condition. However, there were no significant differences in abdominal muscles
      activity in the multiple comparison between conditions (mean difference were
      smaller than the standard deviation in the abdominal muscle activities)
      (padj>0.017), except for differences in both side IO muscle activity between the
      floor (stable surface) and foam roll (padj<0.017) (effect size: 0.79/0.62 (non
      supporting/supporting leg) for foam-roll versus floor). 

PMID- 25066517
TI  - EMG of upper trapezius--electrode sites and association with clavicular
      kinematics.
AB  - The upper trapezius (UT) has been widely studied and related to alterations in
      clavicular kinematics in subject with shoulder disorders. However, the most
      common electrode site used to capture UT EMG is between C7 and the acromion,
      placing the electrodes over the acromial fibers rather than clavicular ones.
      Therefore, this study aimed to investigate the relationship between clavicular
      movements (elevation and retraction) and UT EMG recorded from three electrode
      sites (traditional electrode positioning and two different sites proposed for
      clavicular fibers evaluation). Furthermore, the position associated with the
      highest EMG during maximal isometric voluntary contractions (MVIC), for each
      electrode site, was determined for normalization purposes. EMG was simultaneously
      captured in the three electrode sites of 20 healthy subjects, during MVIC at five
      different positions and during shoulder elevation and abduction in scapular
      plane. Clavicular kinematics was recorded using an electromagnetic tracking
      system during the dynamic contractions. Shoulder abduction with head rotation and
      lateral flexion elicited the highest EMG amplitude on the three electrode sites
      and was used to normalize the signals. A cross-correlation analysis showed high
      correlations between all electrode sites and clavicular movements. However, the
      traditional electrode site seems to record more informative signals in healthy
      subjects. 

PMID- 25066518
TI  - Muscle activity and spine load during pulling exercises: influence of stable and
      labile contact surfaces and technique coaching.
AB  - This study examined pulling exercises performed on stable surfaces and unstable
      suspension straps. Specific questions included: which exercises challenged
      particular muscles, what was the magnitude of resulting spine load, and did
      technique coaching influence results. Fourteen males performed pulling tasks
      while muscle activity, external force, and 3D body segment motion were recorded.
      These data were processed and input to a sophisticated and anatomically detailed
      3D model that used muscle activity and body segment kinematics to estimate muscle
      force, in this way the model was sensitive to each individual's choice of motor
      control for each task. Muscle forces and linked segment joint loads were used to
      calculate spine loads. There were gradations of muscle activity and spine load
      characteristics to every task. It appears that suspension straps alter muscle
      activity less in pulling exercises, compared to studies reporting on pushing
      exercises. The chin-up and pull-up exercises created the highest spine load as
      they required the highest muscle activation, despite the body "hanging" under
      tractioning gravitational load. Coaching shoulder centration through retraction
      increased spine loading but undoubtedly adds proximal stiffness. An exercise
      atlas of spine compression was constructed to help with the decision making
      process of exercise choice for an individual. 

PMID- 25066519
TI  - Cognitive content specificity in anxiety and depressive disorder symptoms: a twin
      study of cross-sectional associations with anxiety sensitivity dimensions across
      development.
AB  - BACKGROUND: The classification of anxiety and depressive disorders has long been
      debated and has important clinical implications. The present study combined a
      genetically sensitive design and multiple time points to investigate cognitive
      content specificity in anxiety and depressive disorder symptoms across anxiety
      sensitivity dimensions, a cognitive distortion implicated in both disorders.
      METHOD: Phenotypic and genetic correlations between anxiety sensitivity
      dimensions, anxiety and depressive disorder symptoms were examined at five waves
      of data collection within childhood, adolescence and early adulthood in two
      representative twin studies (n pairs = 300 and 1372). RESULTS: The physical
      concerns dimension of anxiety sensitivity (fear of bodily symptoms) was
      significantly associated with anxiety but not depression at all waves. Genetic
      influences on physical concerns overlapped substantially more with anxiety than
      depression. Conversely, mental concerns (worry regarding cognitive control) were
      phenotypically more strongly associated with depression than anxiety. Social
      concerns (fear of publicly observable symptoms of anxiety) were associated with
      both anxiety and depression in adolescence. Genetic influences on mental and
      social concerns were shared to a similar extent with both anxiety and depression.
      CONCLUSIONS: Phenotypic patterns of cognitive specificity and broader genetic
      associations between anxiety sensitivity dimensions, anxiety and depressive
      disorder symptoms were similar at all waves. Both disorder-specific and shared
      cognitive concerns were identified, suggesting it is appropriate to classify
      anxiety and depression as distinct but related disorders and confirming the
      clinical perspective that cognitive therapy is most likely to benefit by
      targeting cognitive concerns relating specifically to the individual's presenting
      symptoms across development.

PMID- 25066520
TI  - Discrimination between glioblastoma multiforme and solitary metastasis using
      morphological features derived from the p:q tensor decomposition of diffusion
      tensor imaging.
AB  - The management and treatment of high-grade glioblastoma multiforme (GBM) and
      solitary metastasis (MET) are very different and influence the prognosis and
      subsequent clinical outcomes. In the case of a solitary MET, diagnosis using
      conventional radiology can be equivocal. Currently, a definitive diagnosis is
      based on histopathological analysis on a biopsy sample. Here, we present a
      computerised decision support framework for discrimination between GBM and
      solitary MET using MRI, which includes: (i) a semi-automatic segmentation method
      based on diffusion tensor imaging; (ii) two-dimensional morphological feature
      extraction and selection; and (iii) a pattern recognition module for automated
      tumour classification. Ground truth was provided by histopathological analysis
      from pre-treatment stereotactic biopsy or at surgical resection. Our two
      dimensional morphological analysis outperforms previous methods with high cross
      validation accuracy of 97.9% and area under the receiver operating characteristic
      curve of 0.975 using a neural networks-based classifier.

PMID- 25066521
TI  - Multimodal cortical sensory pathways revealed by sequential transcranial
      electrical stimulation in mice.
AB  - We investigated polysynaptic cortical pathways linking primary to multimodal
      sensory association areas in mice using transcranial flavoprotein imaging
      combined with sequential application of transcranial electrical stimulation
      (TES). Stimulation of primary visual cortex (V1) elicited activity in lateral and
      medial areas of secondary visual cortices (V2), which were reciprocally
      connected. Stimulation of V2 areas elicited activity in area 2. Similarly,
      corticocortical pathways from primary somatosensory cortex (S1) through the
      corresponding secondary somatosensory areas (S2) to area 2 were observed.
      Auditory pathways from primary auditory area (A1) through peripheral region (area
      22) to area 2 and from anterior auditory field to area 2 were also found.
      Stimulation in area 2 elicited activity in part of parietal association cortex
      (PtA), which was reciprocally connected with area 2, and in some areas near the
      midline including retrosplenial cortex (RSA). A cortical pathway from RSA through
      anterior cingulate cortex (aCC) to frontal areas was also visualized. These
      results indicate that area 2, surrounded by visual, somatosensory and auditory
      cortices, may receive inputs from all three primary sensory areas, and may send
      outputs through the parietal association cortex to frontal areas, suggesting that
      area 2 may have an important role in multimodal sensory integration in mice. 

PMID- 25066522
TI  - Proteomic identification of the molecular basis of mammalian CNS growth cones.
AB  - The growth cone, which is a unique structure with high motility that forms at the
      tips of extending axons and dendrites, is crucial to neuronal network formation.
      Axonal growth of the mammalian CNS is most likely achieved by the complicated
      coordination of cytoskeletal rearrangement and vesicular trafficking via many
      proteins. Before recent advances, no methods to identify numerous proteins
      existed; however, proteomics revolutionarily resolved such problems. In this
      review, I summarize the profiles of the mammalian growth cone proteins revealed
      by proteomics as the molecular basis of the growth cone functions, with molecular
      mapping. These results should be used as a basis for understanding the mechanisms
      of the complex mammalian CNS developmental process. 

PMID- 25066523
TI  - Attenuation of the contingency detection effect in the extrastriate body area in
      autism spectrum disorder.
AB  - Detection of the contingency between one's own behavior and consequent social
      events is important for normal social development, and impaired contingency
      detection may be a cause of autism spectrum disorder (ASD). To depict the neural
      underpinnings of this contingency effect, 19 adults with ASD and 22 control
      participants underwent functional MRI while imitating another's actions and their
      actions being imitated by the other. As the extrastriate body area (EBA) receives
      efference copies of one's own movements, we predicted that the EBA would show an
      atypical response during contingency detection in ASD. We manipulated two
      factors: the congruency of the executed and observed actions, and the order of
      action execution and observation. Both groups showed the congruency effect in the
      bilateral EBA during imitation. When action preceded observation, the left EBA of
      the control group showed the congruency effect, representing the response to
      being imitated, indicating contingency detection. The ASD group showed a reduced
      contingency effect in the left EBA. These results indicate that the function of
      the EBA in the contingency detection is altered in ASD. 

PMID- 25066524
TI  - Risk of multiple myeloma is associated with polymorphisms within telomerase genes
      and telomere length.
AB  - Compelling biological and epidemiological evidences point to a key role of
      genetic variants of the TERT and TERC genes in cancer development. We analyzed
      the genetic variability of these two gene regions using samples of 2,267 multiple
      myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant,
      rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72
      0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in
      a subgroup of 140 cases who were chemotherapy-free at the time of blood donation
      and 468 controls, and found that MM patients had longer telomeres compared to
      controls (OR = 1.19; 95% CI: 0.63-2.24; p(trend)  = 0.01 comparing the quartile
      with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of
      decreased disease risk by genetic variants that reduce the efficiency of the
      telomerase complex. This reduced efficiency leads to shorter telomere ends, which
      in turn may also be a marker of decreased MM risk.

PMID- 25066526
TI  - Pilot study of a program delivered within the regular service system in Germany:
      effect of a short-term attachment-based intervention on maternal sensitivity in
      mothers at risk for child abuse and neglect.
AB  - This pilot study examined the effectiveness of a short-term attachment-based
      intervention, the Ulm Model, in a German population at risk for child abuse and
      neglect. The intervention used home visits and video feedback to promote maternal
      sensitivity, and was implemented by trained staff within the health care and
      youth welfare systems. Mothers in the control group (n=33) received standard
      services only, while those in the intervention group (n=63) additionally the Ulm
      Model intervention. The outcomes measured were maternal sensitivity, as assessed
      by the CARE-Index at pre-intervention, after the last session, and at about 6 and
      12 months of age; and infant socio-emotional development, as assessed by the ET6
      6 development test at about 6 and 12 months of age. The moderating effects on
      treatment outcomes of two variables were examined: risk for child abuse (moderate
      vs. high) and type of maternal attachment representation (secure vs. insecure).
      Among participants at moderate risk for child abuse, no differences were found
      between the intervention group and control group in either maternal sensitivity
      or infant development. Among those considered high risk, mothers in the
      intervention group showed a significant increase in maternal sensitivity from pre
      to post-intervention; however, no group differences were seen at follow-up.
      There were some indications that infants of mothers in the intervention group
      showed better emotional development. The variable of maternal attachment
      representation was not a significant moderator for the intervention effect, but
      post hoc analysis indicated that the mean sensitivity of secure mothers was
      significant higher at the 6-month follow-up. 

PMID- 25066525
TI  - Biomaterials in myocardial tissue engineering.
AB  - Cardiovascular disease is the leading cause of death in the developed world, and
      as such there is a pressing need for treatment options. Cardiac tissue
      engineering emerged from the need to develop alternative sources and methods of
      replacing tissue damaged by cardiovascular diseases, as the ultimate treatment
      option for many who suffer from end-stage heart failure is a heart transplant. In
      this review we focus on biomaterial approaches to augmenting injured or impaired
      myocardium, with specific emphasis on: the design criteria for these
      biomaterials; the types of scaffolds - composed of natural or synthetic
      biomaterials or decellularized extracellular matrix - that have been used to
      develop cardiac patches and tissue models; methods to vascularize scaffolds and
      engineered tissue; and finally, injectable biomaterials (hydrogels) designed for
      endogenous repair, exogenous repair or as bulking agents to maintain ventricular
      geometry post-infarct. The challenges facing the field and obstacles that must be
      overcome to develop truly clinically viable cardiac therapies are also discussed.

PMID- 25066527
TI  - Terminating hepatocyte proliferation during liver regeneration: the roles of two
      members of the same family (CCAAT-enhancer-binding protein alpha and beta) with
      opposing actions.

PMID- 25066529
TI  - Imaging wavelength and light penetration depth for water content distribution
      measurement of skin.
AB  - BACKGROUND/PURPOSE: We investigate the measurement sensitivity for the water
      content distribution in Near-infrared (NIR) imaging ranging up to 2 MUm. METHODS:
      To evaluate the sensitivity, our attention is focused to the light penetration
      depth in the skin tissue because the thickness of a layer where the water content
      can be varied is very thin and deep light penetration decreases the signal
      variation. The light penetration depths in the wavelengths of 1300, 1450, and
      1920 nm are calculated theoretically based on the Monte Carlo light transport
      simulation. RESULTS: It is clarified that the wavelength of 1920 nm gives the
      smallest penetration depth. A NIR imaging experiment is demonstrated to verify
      the difference of imaging sensitivity. The experiment result shows that the NIR
      image taken at 1920 nm gives the most sensitive measurement of the water content
      distribution in skin.

PMID- 25066528
TI  - Prone extralevator abdominoperineal excision of the rectum with porcine collagen
      perineal reconstruction (PermacolTM): high primary perineal wound healing rates.
AB  - PURPOSE: Extralevator abdominoperineal excision of the rectum (elAPER) is
      arguably the modern surgical approach to low rectal cancer and yet results in
      large defects that may necessitate plastic surgical reconstruction. This study
      aims to evaluate the quality of prone elAPER surgery with PermacolTM repair of
      the perineum. The primary end point studied was the rate of primary perineal
      wound healing. METHODS: Data were prospectively collected for consecutive
      patients having prone elAPER at a single institution to assess surgical morbidity
      together with pathological and cancer-specific outcomes. RESULTS: Between 2006
      and 2012, 48 patients had prone elAPER with median age of 63 (40-86). Thirty-four
      patients (72.3%) received neoadjuvant treatment. Median length of stay was 9 days
      (6-66). With a prone approach, three patients had specimen perforation (6.4%) and
      seven patients had circumferential margin involvement (14.9%). Complete perineal
      wound healing was achieved in 34 patients (73.9%) at 4 weeks. Four patients
      (8.3%) were unhealed at 6 months; one patient required a perineal sinus to be
      laid open, and another patient required plastic surgical reconstruction. No
      perineal wound herniae have been identified during follow-up. CONCLUSIONS:
      Acceptable oncological outcomes are achieved with the prone extralevator
      approach. The technique achieves high rates of primary healing, making it an
      attractive option in centres without access to plastic reconstructive expertise.

PMID- 25066530
TI  - Lysobacter capsici AZ78 produces cyclo(L-Pro-L-Tyr), a 2,5-diketopiperazine with
      toxic activity against sporangia of Phytophthora infestans and Plasmopara
      viticola.
AB  - AIMS: To investigate low molecular weight compounds produced in vitro by
      Lysobacter capsici AZ78 and their toxic activity against sporangia of plant
      pathogenic oomycetes. METHODS AND RESULTS: Assays carried out in vitro showed
      that L. capsici AZ78 drastically inhibits the growth of plant pathogenic
      oomycetes. Accordingly, the preventive application of culture filtrates of L.
      capsici AZ78 on grapevine and tomato plants reduced the infections, respectively,
      caused by Plasmopara (Pl.) viticola and Phytophthora infestans. The subsequent
      chemical analysis of the culture filtrates of L. capsici AZ78 by spectroscopic
      (essentially 1D and 2D (1)H NMR and (13)C NMR and ESI MS spectra) and optical
      methods led to the identification of the 2,5-diketopiperazine cyclo(L-Pro-L-Tyr)
      that inhibited the development of P. infestans sporangia in vitro and on tomato
      leaves. Furthermore, a genomic region with high sequence identity with genes
      coding for a hybrid polyketide synthase and nonribosomal peptide synthetase was
      detected in L. capsici AZ78. CONCLUSIONS: Lysobacter capsici AZ78 produces
      cyclo(L-Pro-L-Tyr) in vitro that was effective in killing the sporangia of P.
      infestans and Pl. viticola in vitro. Moreover, this low molecular weight compound
      prevents the occurrence of late blight lesions when applied on tomato leaves.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The application of L. capsici AZ78 cells or
      its own culture filtrates effectively controls both P. infestans and Pl.
      viticola. Cyclo(L-Pro-L-Tyr) produced by L. capsici AZ78 is toxic against
      sporangia of both these oomycetes. These data enforce the potential in the use of
      Lysobacter members for the control of plant pathogenic oomycetes and provide the
      basis for the development of new low-impact fungicides based on cyclo(L-Pro-L
      Tyr).

PMID- 25066531
TI  - Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model
      of retinal degeneration.
AB  - Photoreceptor (PR) cells are prone to accumulation of reactive oxygen species
      (ROS) and oxidative stress. An imbalance between the production of ROS and
      cellular antioxidant defenses contributes to PR degeneration and blindness in
      many different ocular disease states. Yttrium oxide (Y2O3) nanoparticles (NPs)
      are excellent free radical scavengers owing to their nonstoichiometric crystal
      defects. Here we utilize a murine light-stress model to test the efficacy of Y2O3
      NPs (~10-14nm in diameter) in ameliorating retinal oxidative stress-associated
      degeneration. Our studies demonstrate that intravitreal injections of these NPs
      at doses ranging from 0.1 to 5.0uM 2 weeks before acute light stress protect PRs
      from degeneration. This protection is reflected both structurally (i.e.,
      decreased light-associated thinning of the outer nuclear layer) and functionally
      (i.e., preservation of scotopic and photopic electroretinogram amplitudes). We
      also observe preservation of structure and function when NPs are delivered
      immediately after acute light stress, although the magnitude of the preservation
      is smaller, and only doses ranging from 1.0 to 5.0uM were effective. We show that
      the Y2O3 NPs are nontoxic and well tolerated after intravitreal delivery. Our
      results suggest that Y2O3 NPs have astonishing antioxidant benefits and, with
      further exploration, may be an excellent strategy for the treatment of oxidative
      stress associated with multiple forms of retinal degeneration.

PMID- 25066532
TI  - Seizure threshold and the half-age method in bilateral electroconvulsive therapy
      in Japanese patients.
AB  - AIM: Seizure threshold (ST) in electroconvulsive therapy (ECT) has not been
      reported previously in Japanese patients. We investigated ST in bilateral ECT in
      Japanese patients using the dose-titration method. The associations between
      demographic and clinical characteristics and ST were analyzed to identify the
      predictors of ST. Finally, the validity of the half-age method for the stimulus
      dose was evaluated. METHODS: Fifty-four Japanese patients with mood disorder,
      schizophrenia, and other psychotic disorders received an acute course of
      bilateral ECT using a brief-pulse device. ST was determined at the first session
      using a fixed titration schedule. ST was correlated with age, sex, body mass
      index, history of previous ECT, and psychotropic drugs on multiple regression
      analysis. Furthermore, the rate of accomplished seizures was calculated using the
      half-age method. RESULTS: Mean ST was 136 mC. ST was influenced by age, sex,
      history of previous ECT, and medication with benzodiazepines. The accomplished
      seizure rate using the half-age method was 72%, which was significantly lower in
      men and subjects on benzodiazepines. CONCLUSION: ST in Japanese patients was
      equal to or slightly higher than that previously reported in other ethnic groups,
      which might be attributable, at least in part, to high prevalence of and large
      dose benzodiazepine prescription. Higher age, male gender, no history of ECT, and
      benzodiazepines were related to higher ST. The half-age method was especially
      useful in female patients and subjects without benzodiazepine medication.

PMID- 25066534
TI  - Assessment of immature platelet fraction and immature reticulocyte fraction as
      predictors of engraftment after hematopoietic stem cell transplantation.
AB  - INTRODUCTION: Engraftment is a critical milestone of the hematopoietic stem cell
      transplantation (HSCT) process. The immature platelet fraction (IPF) and immature
      reticulocyte fraction (IRF) are considered early indicators of bone marrow
      recovery. The objective of this study was to assess these parameters as
      predictors of HSCT engraftment. METHODS: Neutrophil and platelet engraftment were
      defined as the first of three consecutive days with an absolute neutrophil count
      >0.5 * 10(9) /L or platelet count >20 * 10(9) /L, respectively. The IRF cutoff
      was 12%. Two IPF cutoffs were used: >6.2% and >10%. RESULTS: The study sample
      comprised 44 patients, of whom 24 had undergone autologous HSCT and 20 had
      undergone allogeneic HSCT. Absolute neutrophil counts >0.5 * 10(9) /L were
      preceded by IRF >12% in 86% of patients (38 of 44). Platelet counts >20 * 10(9)
      /L were preceded by an IPF >6.2% in 90% of patients (37 of 41) and by an IPF >10%
      in 63% of patients (26 of 41). CONCLUSION: The results show that IRF and IPF are
      engraftment predictors. Peak in IPF was observed before rise in platelet count,
      while IRF rises before absolute neutrophil count (ANC) and persists increased.
      This indicates that IRF and IPF can be considered as new tools for hematopoietic
      assessment after HSCT.

PMID- 25066533
TI  - Mental health in Dutch adolescents: a TRAILS report on prevalence, severity, age
      of onset, continuity and co-morbidity of DSM disorders.
AB  - BACKGROUND: With psychopathology rising during adolescence and evidence
      suggesting that adult mental health burden is often due to disorders beginning in
      youth, it is important to investigate the epidemiology of adolescent mental
      disorders. METHOD: We analysed data gathered at ages 11 (baseline) and 19 years
      from the population-based Dutch TRacking Adolescents' Individual Lives Survey
      (TRAILS) study. At baseline we administered the Achenbach measures (Child
      Behavior Checklist, Youth Self-Report) and at age 19 years the World Health
      Organization's Composite International Diagnostic Interview version 3.0 (CIDI
      3.0) to 1584 youths. RESULTS: Lifetime, 12-month and 30-day prevalences of any
      CIDI-DSM-IV disorder were 45, 31 and 15%, respectively. Half were severe. Anxiety
      disorders were the most common but the least severe whereas mood and behaviour
      disorders were less prevalent but more severe. Disorders persisted, mostly by
      recurrence in mood disorders and chronicity in anxiety disorders. Median onset
      age varied substantially across disorders. Having one disorder increased
      subjects' risk of developing another disorder. We found substantial homotypic and
      heterotypic continuity. Baseline problems predicted the development of
      diagnosable disorders in adolescence. Non-intact families and low maternal
      education predicted externalizing disorders. Most morbidity concentrated in 5-10%
      of the sample, experiencing 34-55% of all severe lifetime disorders. CONCLUSIONS:
      At late adolescence, 22% of youths have experienced a severe episode and 23% only
      mild episodes. This psychopathology is rather persistent, mostly due to
      recurrence, showing both monotypic and heterotypic continuity, with family
      context affecting particularly externalizing disorders. High problem levels at
      age 11 years are modest precursors of incident adolescent disorders. The burden
      of mental illness concentrates in 5-10% of the adolescent population.

PMID- 25066535
TI  - Organizational strategy use in children aged 5-7: standardization and validity of
      the Rey Complex Figure Organizational Strategy Score (RCF-OSS).
AB  - This study investigated psychometric properties (standardization and validity) of
      the Rey Complex Figure Organizational Strategy Score (RCF-OSS) in a sample of 217
      healthy children aged 5-7 years. Our results showed that RCF-OSS performance
      changes significantly between 5 and 7 years of age. While most 5-year-olds used a
      local approach when copying the Rey-Osterrieth Complex Figure (ROCF), 7-year-olds
      increasingly adopted a global approach. RCF-OSS performance correlated
      significantly, but moderately with measures of ROCF accuracy, executive
      functioning (fluency, working memory, reasoning), and non-executive functioning
      (visual-motor integration, visual attention, processing speed, numeracy). These
      findings seem to indicate that RCF-OSS performance reflects a range of cognitive
      skills at 5 to 7 years of age, including aspects of executive and non-executive
      functioning.

PMID- 25066536
TI  - Left renal nerves stimulation facilitates ischemia-induced ventricular arrhythmia
      by increasing nerve activity of left stellate ganglion.
AB  - INTRODUCTION: Renal sympathetic nerve (RSN) activity plays a key role in systemic
      sympathetic hyperactivity. Previous studies have shown that cardiac sympathetic
      hyperactivity, especially the left stellate ganglion (LSG), contributes to the
      pathogenesis of ventricular arrhythmias (VAs) after acute myocardial infarction
      (AMI). METHODS AND RESULTS: Twenty-eight dogs received 3 hours of continuous left
      sided electrical stimulation of RSN (LRS; Group-1, n = 9), sham RSN stimulation
      (Group-2, n = 9), or LSG ablation plus 3 hours of LRS (Group-3, n = 10) were
      included. AMI was induced by ligating the proximal left anterior descending
      coronary artery. LRS was performed using electrical stimulation on the adventitia
      of left renal artery at the voltage increasing the systolic blood pressure (BP)
      by 10%. BP, heart rate variability (HRV), serum norepinephrine (NE) level, and
      LSG function were measured at baseline and the end of each hour of LRS. C-fos and
      nerve growth factor (NGF) protein expressed in the LSG were examined in Group-1
      and Group-2. Compared with baseline, 3 hours of LRS induced a significant
      increase in BP, sympathetic indices of HRV, serum NE level, and LSG function. The
      incidence of VAs in Group-1 was significantly higher than other groups. The
      expression of c-fos and NGF protein in the LSG was significantly higher in Group
      1 than Group-2. CONCLUSION: Three hours of LRS induces both systemic and cardiac
      sympathetic hyperactivity and increases the incidence of ischemia-induced VAs.

PMID- 25066537
TI  - Natural course of cannabis use disorders.
AB  - BACKGROUND: Despite its importance as a public health concern, relatively little
      is known about the natural course of cannabis use disorders (CUDs). The primary
      objective of this research was to provide descriptive data on the onset, recovery
      and recurrence functions of CUDs during the high-risk periods of adolescence,
      emerging adulthood and young adulthood based on data from a large prospective
      community sample. METHOD: Probands (n = 816) from the Oregon Adolescent
      Depression Project (OADP) participated in four diagnostic assessments (T1-T4)
      between the ages of 16 and 30 years, during which current and past CUDs were
      assessed. RESULTS: The weighted lifetime prevalence of CUDs was 19.1% with an
      average onset age of 18.6 years. Although gender was not significantly related to
      the age of initial CUD onset, men were more likely to be diagnosed with a
      lifetime CUD. Of those diagnosed with a CUD episode, 81.8% eventually achieved
      recovery during the study period. Women achieved recovery significantly more
      quickly than men. The recurrence rate (27.7%) was relatively modest, and most
      likely to occur within the first 36 months following the offset of the first CUD
      episode. CUD recurrence was uncommon after 72 months of remission and recovery.
      CONCLUSIONS: CUDs are relatively common, affecting about one out of five persons
      in the OADP sample prior to the age of 30 years. Eventual recovery from index CUD
      episodes is the norm, although about 30% of those with a CUD exhibit a generally
      persistent pattern of problematic use extending 7 years or longer.

PMID- 25066540
TI  - One proboscis, two tasks: adaptations to blood-feeding and nectar-extracting in
      long-proboscid horse flies (Tabanidae, Philoliche).
AB  - Female Pangoniinae in the tabanid fly genus Philoliche can display remarkably
      elongated proboscis lengths, which are adapted for both blood- and nectar
      feeding. Apart from their role as blood-sucking pests, they represent important
      pollinators of the South African flora. This study examines the morphology of the
      feeding apparatus of two species of long-proboscid Tabanidae: Philoliche rostrata
      and Philoliche gulosa - both species display adaptations for feeding from a
      diverse guild of long-tubed flowers, and on vertebrate blood. The heavily
      sclerotised proboscis can be divided into two functional units. The short,
      proximal piercing part is composed of the labrum-epipharynx unit, the hypopharynx
      and paired mandible and maxilla. The foldable distal part is composed of the
      prementum of the labium which solely forms the food canal and is responsible for
      nectar uptake via the apical labella. The proboscis works as a drinking straw,
      relying on a pressure gradient provided by a two-part suction pump in the head.
      Both proboscis and body lengths and suction pump dimensions show a significantly
      correlated allometric relationship with each other. This study provides detailed
      insights into the adaptations for a dual diet using an elongated sucking
      proboscis, and considers these adaptations in the context of the evolution of
      nectar feeding in Brachycera. 

PMID- 25066541
TI  - Antioxidant activity of hyaluronic acid investigated by means of
      chemiluminescence of equine neutrophil bursts and electron paramagnetic resonance
      spectroscopy.
AB  - Activated neutrophils (PMNs), the ROS/RNS released by PMNs and the derived
      inflammatory processes are involved in the pathogenesis and progression of human
      inflammatory airway diseases. Similar diseases are also present in horses which
      suffer from recurrent airway obstruction (RAO), exercise-induced pulmonary
      haemorrhage (EIPH) and inflammatory airway diseases (IAD). Hyaluronic acid (HA)
      plays numerous roles in modulating inflammatory processes. The aim of this study
      was to examine whether a preparation of HA (MW 900 000 Da) interferes with
      ROS/RNS during the course of equine PMN respiratory bursts, and to establish the
      lowest concentration at which it still has antioxidant activity by means of
      luminol-amplified chemiluminescence (LACL). Electron paramagnetic resonance (EPR)
      spectroscopy was also used to investigate the direct antiradical activity of HA.
      The hydroxyl radical was significantly scavenged in a concentration-dependent
      manner at HA concentrations ranging from 2.5 to 0.16 mg/mL. Superoxide anion,
      Tempol radical and the ABTS(*+) were significantly inhibited at concentrations
      ranging from 2.5 to 0.62 mg/mL. The LACL of stimulated equine neutrophils showed
      that HA induced a statistically significant concentration-effect reduction from 5
      mg/mL to 1.25 mg/mL. These findings were confirmed also when l-Arg was added to
      investigate the inhibition of the resulting peroxynitrite anion. Our findings
      indicate that, in addition to the human use, HA can also be used to antagonize
      the oxidative stress generated by free radicals in horses peripheral blood
      mononuclear cells (PBMCs). In order to achieve therapeutic concentrations, a
      direct aerosol administration to horses with horse respiratory diseases can be
      considered, as this route of application is also recommended in human medicine.

PMID- 25066542
TI  - Intensification treatment based on early FDG-PET in patients with high-risk
      diffuse large B-cell lymphoma: a phase II GELTAMO trial.
AB  - We conducted a multicentre, phase II study of interim positron emission
      tomography (PET) as a guide to risk-adapted therapy in high-risk patients with
      newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving
      negative fluorodeoxyglucose (FDG)-PET after three courses of R-MegaCHOP
      (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received
      three additional courses, whereas PET-positive patients received two courses of R
      IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide,
      cytarabine, melphalan) and autologous stem-cell transplantation. The primary
      endpoint was progression-free survival (PFS). 71 patients (median age 55 years,
      range 25-69) were enrolled. With a median follow-up of 42.8 months (range 7.2
      58.4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%,
      respectively, for the global series. Patients in complete remission after interim
      PET (N = 36) had significantly better 3-year PFS than those with partial response
      (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2.6, 95% confidence interval (CI) =
      1.02-6.65] but not a statistically significant longer OS. A retrospective PET
      central review was done for 51 patients. According to semiquantitative analysis,
      3-year PFS (81% vs. 33%; HR = 6.9, 95% CI = 2.35-20.6) and OS (95% vs. 33%, HR =
      19.4, 95% CI = 3.89-97.0) were significantly better for negative than for
      positive interim PET patients. Early PET assessment is valuable for risk
      stratification in DLBCL; for this purpose semiquantitative evaluation is a better
      predictor than visual criteria.

PMID- 25066543
TI  - Variation among genotypes in responses to increasing temperature in a marine
      parasite: evolutionary potential in the face of global warming?
AB  - Climates are changing worldwide, and populations are under selection to adapt to
      these changes. Changing temperature, in particular, can directly impact
      ectotherms and their parasites, with potential consequences for whole ecosystems.
      The potential of parasite populations to adapt to climate change largely depends
      on the amount of genetic variation they possess in their responses to
      environmental fluctuations. This study is, to our knowledge, the first to look at
      differences among parasite genotypes in response to temperature, with the goal of
      quantifying the extent of variation among conspecifics in their responses to
      increasing temperature. Snails infected with single genotypes of the trematode
      Maritrema novaezealandensis were sequentially acclimatised to two different
      temperatures, 'current' (15 degrees C) and 'elevated' (20 degrees C), over long
      periods. These temperatures are based on current average field conditions in the
      natural habitat and those predicted to occur during the next few decades. The
      output and activity of cercariae (free-swimming infective stages emerging from
      snails) were assessed for each genotype at each temperature. The results indicate
      that, on average, both cercarial output and activity are higher at the elevated
      acclimation temperature. More importantly, the output and activity of cercariae
      are strongly influenced by a genotype-by-temperature interaction, such that
      different genotypes show different responses to increasing temperature. Both the
      magnitude and direction (increase or decrease) of responses to temperature varied
      widely among genotypes. Therefore, there is much potential for natural selection
      to act on this variation, and predicting how the trematode M. novaezealandensis
      will respond to the climate changes predicted for the next century will prove
      challenging. 

PMID- 25066544
TI  - Amygdala and anterior cingulate resting-state functional connectivity in
      borderline personality disorder patients with a history of interpersonal trauma.
AB  - BACKGROUND: Studies in borderline personality disorder (BPD) have consistently
      revealed abnormalities in fronto-limbic brain regions during emotional,
      somatosensory and cognitive challenges. Here we investigated changes in resting
      state functional connectivity (RSFC) of three fronto-limbic core regions of
      specific importance to BPD. METHOD: Functional magnetic resonance imaging data
      were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC,
      matched for age, sex and education) during rest. The amygdala, and the dorsal and
      ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC
      patterns of a medial temporal lobe network, the salience network and default mode
      network. The Dissociation Experience Scale (DES), a measure of trait
      dissociation, was additionally used as a predictor of RSFC with these seed
      regions. RESULTS: Compared with HC, BPD patients showed a trend towards increased
      RSFC between the amygdala and the insula, orbitofrontal cortex and putamen.
      Compared with controls, patients furthermore exhibited diminished negative RSFC
      between the dorsal ACC and posterior cingulate cortex, a core region of the
      default mode network, and regions of the dorsomedial prefrontal cortex. Last,
      increased negative RSFC between the ventral ACC and medial occipital regions was
      observed in BPD patients. DES scores were correlated with amygdala connectivity
      with the dorsolateral prefrontal cortex and fusiform gyrus. CONCLUSIONS: Our
      findings suggest alterations in resting-state networks associated with processing
      of negative emotions, encoding of salient events, and self-referential processing
      in individuals with BPD compared with HC. These results shed more light on the
      role of abnormal brain connectivity in BPD.

PMID- 25066545
TI  - The use of sunitinib in renal cell carcinoma: where are we now?
AB  - Sunitinib malate (SutentTM) is an inhibitor of multiple protein tyrosine kinases
      that shows antitumor and antiangiogenic activities. In a randomized Phase III
      trial of treatment-naive patients with metastatic renal cell carcinoma (mRCC),
      patients treated with sunitinib showed a significant improvement in progression
      free survival compared with those treated with IFN-alpha. Sunitinib also
      exhibited antitumor activity in unselected RCC patients, including those with who
      were refractory to treatment, had non-clear cell histology brain metastases, or
      an Eastern Cooperative Oncology Group performance status >1. Typical side effects
      of sunitinib malate are fatigue, asthenia, diarrhea, skin rash, stomatitis, hand
      foot skin syndrome, hypothyroidism and hematological abnormalities. Hypertension,
      other toxicities may serve as biomarkers for improved clinical outcomes in
      sunitinib treatment. Currently, sunitinib remains the gold standard of care in
      the treatment of mRCC. 

PMID- 25066546
TI  - Myxopapillary ependymoma in children: a study of 11 cases and a comparison with
      the adult experience.
AB  - BACKGROUND: Myxopapillary ependymomas (MEPN) are uncommon tumors of the central
      nervous system, mainly occurring within the conus medullaris-filum terminale.
      MEPNs can also present in the skin and underlying soft tissues of the
      sacrococcygeal region. The incidence of extramedullary MEPNs in children is
      unclear. PROCEDURE: We retrospectively reviewed our institutional files for MEPN
      cases between the years 1990-2012. A total of 11 pediatric and 38 adult cases
      were identified and compared to determine differences between these two distinct
      age groups. RESULTS: There were 40 (82%) tumors arising in the spine and nine
      (18%) in extramedullary sites. Pathologic examination revealed that
      extramedullary and spinal MEPNs were indistinguishable morphologically and
      immunophenotypically. Among the 11 children with MEPNs, seven had tumors
      presenting in extramedullary sites whereas only two adults (5%) had
      extramedullary tumors; this difference was highly significant (P < 0.0001). The
      lumbosacral portion of the spinal cord was the primary site for the remaining 40
      MEPNs, four (10%) of which presented in children. One extramedullary MEPN (9%)
      recurred in a 45-year-old woman, and five (11%) of 40 spinal tumors recurred
      and/or metastasized; two of four children with spinal MEPNs developed recurrences
      and a manifestation to the aggressive nature of the latter tumor in the spinal
      cord of children. CONCLUSIONS: Based upon our experience, MEPN in children is
      more likely to present in the extramedullary soft tissues of the sacrococcygeal
      region where its behavior is more indolent than those tumors arising in the
      spinal cord in children.

PMID- 25066547
TI  - Structural and functional imaging of the hippocampus in young people at familial
      risk of depression.
AB  - BACKGROUND: Major depression is associated with abnormalities in the function and
      structure of the hippocampus. However, it is unclear whether these abnormalities
      might also be present in people 'at risk' of illness. METHOD: We studied 62 young
      people (mean age 18.8 years) at familial risk of depression (FH+) but who had
      never been depressed themselves. Participants underwent magnetic resonance
      imaging to assess hippocampal structure and neural responses to a task designed
      to activate hippocampal memory networks. Magnetic resonance spectroscopy was used
      to measure levels of a combination of glutamine and glutamate (Glx) in the right
      hippocampus. A total of 59 matched controls with no history of mood disorder in a
      first-degree relative underwent the same investigations. RESULTS: Hippocampal
      volume did not differ between FH+ participants and controls; however, relative to
      controls, during the memory task, FH+ participants showed increased activation in
      brain regions encompassing the insular cortices, putamen and pallidum as well as
      the dorsal anterior cingulate cortex (ACC). FH+ participants also had increased
      hippocampal levels of Glx. CONCLUSIONS: Euthymic individuals with a parental
      history of depression demonstrate increased activation of hippocampal-related
      neural networks during a memory task, particularly in brain regions involved in
      processing the salience of stimuli. Changes in the activity of the ACC replicate
      previous findings in FH+ participants using different psychological tasks; this
      suggests that task-related abnormalities in the ACC may be a marker of
      vulnerability to depression. Increased levels of Glx in the hippocampus might
      also represent a risk biomarker but follow-up studies will be required to test
      these various possibilities.

PMID- 25066548
TI  - Extract of Irish potatoes (Solanum tuberosum L.) decreases body weight gain and
      adiposity and improves glucose control in the mouse model of diet-induced
      obesity.
AB  - Both sexes of mice were fed a high fat diet (HFD) for 10 weeks without and with
      polyphenolic-rich potato extracts (PRPE) of cultivars Onaway and Russet Burbank.
      PRPE attenuated weight gain in male and female mice by as much as 63.2%, which
      was associated mostly with a reduction in adiposity. Mice receiving PRPE showed
      enhanced capacity for blood glucose clearance. Sex differences regarding the
      impact of HFD and PRPE on plasma levels of insulin, ghrelin, leptin, gastric
      inhibitory peptide, and resistin were noted. PRPE may serve as part of a
      preventative dietary strategy against the development of obesity and type 2
      diabetes. 

PMID- 25066549
TI  - Dehydrocostuslactone inhibits LPS-induced inflammation by p38MAPK-dependent
      induction of hemeoxygenase-1 in vitro and improves survival of mice in CLP
      induced sepsis in vivo.
AB  - We investigated the hypothesis that the administration of dehydrocostuslactone
      (DL), a sesquiterpene lactone found in Saussurea lappa Clarke (Compositae), might
      reduce organ failure and increase survival in a cecal ligation and puncture (CLP)
      induced mouse model of sepsis due to HO-1 induction. Treatment of RAW264.7 cells
      with DL increased HO-1 expression in a time- and concentration-dependent manner,
      and this up-regulation of HO-1 by DL was significantly inhibited by silencing
      either Nrf2 and p38 or treating cells with SB203580 (a p38MAPK inhibitor), but it
      was not inhibited in the presence of SP600125 (an ERK inhibitor), PD98059 (a JNK
      inhibitor), or LY294002 (PI3K inhibitor). As expected, DL concentration
      dependently inhibited the expressions of inducible nitric oxide synthase (iNOS)
      and cyclooxygenase (COX-2), and the productions of NO and PGE2 in LPS-activated
      cells, and these inhibitions were reversed by silencing HO-1. Most importantly,
      administration of DL significantly reduced mortality and reduced serum IL-1beta
      and TNF-alpha and the infiltration of macrophages into liver tissues of CLP-mice.
      Inducible NOS expression in lung and liver tissues of CLP-mice was reduced by DL,
      which was reversed by the co-administration of zinc-protoporphyrin IX (ZnPPIX; a
      competitive inhibitor of HO-1). Our findings indicate that DL might be useful for
      the treatment of sepsis. 

PMID- 25066550
TI  - The new era of clinical research: using data for multiple purposes.

PMID- 25066551
TI  - Independent data monitoring committees: preparing a path for the future.
AB  - Independent data monitoring committees (IDMCs) were introduced to monitor patient
      safety and study conduct in randomized clinical trials (RCTs), but certain
      challenges regarding the utilization of IDMCs have developed. First, the roles
      and responsibilities of IDMCs are expanding, perhaps due to increasing trial
      complexity and heterogeneity regarding medical, ethical, legal, regulatory, and
      financial issues. Second, no standard for IDMC operating procedures exists, and
      there is uncertainty about who should determine standards and whether standards
      should vary with trial size and design. Third, considerable variability in
      communication pathways exist across IDMC interfaces with regulatory agencies,
      academic coordinating centers, and sponsors. Finally, there has been a
      substantial increase in the number of RCTs using IDMCs, yet there is no set of
      qualifications to help guide the training and development of the next generation
      of IDMC members. Recently, an expert panel of representatives from government,
      industry, and academia assembled at the Duke Clinical Research Institute to
      address these challenges and to develop recommendations for the future
      utilization of IDMCs in RCTs. 

PMID- 25066553
TI  - A critical review of hemodynamic changes and left ventricular remodeling after
      surgical aortic valve replacement and percutaneous aortic valve replacement.
AB  - The introduction of transcatheter aortic valve replacement (TAVR) in clinical
      practice has widened options for symptomatic patients at high surgical risk;
      however, it is not known whether TAVR has equivalent or prolonged benefits in
      terms of left ventricular (LV) remodeling. METHODS: To explore the relative
      hemodynamic benefits and postoperative LV remodeling associated with TAVR and
      surgical aortic valve replacement (SAVR), we performed a critical review of the
      available literature. A total of 67 studies were included in this systematic
      review. RESULTS: There is at least equivalent if not slightly superior
      hemodynamic performance of TAVR over SAVR, and TAVR showed lower prosthesis
      patient mismatch compared with SAVR. However, LV mass appears to regress to a
      greater degree after SAVR compared with TAVR. Aortic regurgitation, paravalvular
      in particular, is more common after TAVR than SAVR, although it is rarely more
      than moderate in severity. Improvements in diastolic function and mitral
      regurgitation are reported in only a handful of studies each and could not be
      compared across prosthesis types. CONCLUSIONS: The published data support the
      hemodynamic comparability of SAVR and TAVR, with the higher incidence of
      prosthesis-patient mismatch in SAVR offset by higher incidence of paravalvular
      leak in TAVR. These results highlight the need for further studies focusing on
      hemodynamic changes after valve therapy.

PMID- 25066552
TI  - Designing effective drug and device development programs for hospitalized heart
      failure: a proposal for pretrial registries.
AB  - Recent international phase III clinical trials of novel therapies for
      hospitalized heart failure (HHF) have failed to improve the unacceptably high
      postdischarge event rate. These large studies have demonstrated notable
      geographic and site-specific variation in patient profiles and enrollment.
      Possible contributors to the lack of success in HHF outcome trials include
      challenges in selecting clinical sites capable of (1) providing adequate numbers
      of appropriately selected patients and (2) properly executing the study protocol.
      We propose a "pretrial registry" as a novel tool for improving the efficiency and
      quality of international HHF trials by focusing on the selection and cultivation
      of high-quality sites. A pretrial registry may help assess a site's ability to
      achieve adequate enrollment of the target patient population, integrate protocol
      requirements into clinical workflow, and accomplish appropriate follow-up.
      Although such a process would be associated with additional upfront resource
      investment, this appropriation may be modest in comparison with the downstream
      costs associated with maintenance of poorly performing sites, failed clinical
      trials, and the global health and economic burden of HHF. This review is based on
      discussions between scientists, clinical trialists, and regulatory
      representatives regarding methods for improving international HHF trials that
      took place at the United States Food and Drug Administration on January 12th,
      2012. 

PMID- 25066555
TI  - Rationale and design of the AngeLmed for Early Recognition and Treatment of STEMI
      trial: a randomized, prospective clinical investigation.
AB  - Significant improvements in door-to-balloon times have led to a reduction in
      mortality in ST-segment elevation myocardial infarction; however, mean symptom-to
      door times remain at 2 to 3 hours. An intracardiac electrogram monitoring device
      may be beneficial in high-risk patients by alerting them to rapidly progressive
      ST-segment changes indicative of acute coronary occlusion. The Cardiosaver and
      DETECT phase I clinical studies demonstrated the safety, feasibility, and
      potential benefit of using an intracardiac electrogram monitoring device to alert
      the patient to seek medical attention. The goal of the randomized, prospective
      ALERTS Trial (Clinicaltrials.gov no. NCT00781118) is to evaluate the efficacy of
      an implantable monitoring device (IMD) in reducing the composite of either
      cardiac or unexplained death, new Q-wave myocardial infarction, or symptom-to
      door time of >2 hours for confirmed thrombotic events. The IMD alerts the patient
      in real time when ST-segment deviation from a personalized baseline exceeds the
      trigger threshold. The trial is designed to enroll high-risk post-acute coronary
      syndrome patients or patients with previous multivessel coronary artery bypass
      surgery. All patients have the IMD implanted, with 1:1 unblinded randomization to
      the alerting feature being either turned on versus turned off for the first 6
      months. Randomization occurs at the first follow-up visit, 7 to 14 days after the
      implantation of the IMD. Subjects then return for follow-up visits at months 1,
      3, and 6 and thereafter every 6 months until closure of the investigational
      device exemption. Subjects who cannot be implanted successfully or who have the
      device explanted are removed from the study and followed up for a minimum of 30
      days post-procedure. If a subject experiences a device-related complication
      and/or adverse experience, the subject is followed up until resolution or until
      the condition becomes stable and no further change is anticipated. 

PMID- 25066554
TI  - Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II:
      rationale and design of the ORBIT-AF II registry.
AB  - BACKGROUND: Recent clinical trials have demonstrated the safety and efficacy of
      several non-vitamin K oral anticoagulants (NOACs) for the treatment of atrial
      fibrillation (AF). However, there are limited data on their use and outcomes in
      routine clinical practice, particularly among patients newly diagnosed as having
      AF and patients with AF recently transitioned to a NOAC. METHODS/DESIGN: ORBIT-AF
      II is a multicenter, national registry of patients with AF that is enrolling up
      to 15,000 newly diagnosed patients with AF and/or those with AF recently
      transitioned to a NOAC from 300 US outpatient practices. These patients will be
      followed for up to 2 years, including clinical status, outcomes (major adverse
      cardiovascular events, bleeding), and management of anticoagulation surrounding
      bleeding events. In addition, detailed data regarding the use of these agents in
      and around cardiac procedures, their complications, and management of such
      complications will be collected. CONCLUSIONS: The ORBIT-AF II registry will
      provide valuable insights into the safety and effectiveness of NOACs used in AF
      in community practice settings.

PMID- 25066556
TI  - Does optical coherence tomography optimize results of stenting? Rationale and
      study design.
AB  - BACKGROUND: To date, no randomized study has investigated the value of optical
      coherence tomography (OCT) in optimizing the results of coronary angioplasty for
      non-ST-segment elevation acute coronary syndromes. METHODS: DOCTORS is a
      randomized, prospective, multicenter, open-label clinical trial to evaluate the
      utility of OCT to optimize results of angioplasty of a lesion responsible for non
      ST-elevation acute coronary syndromes. Patients (n = 250) will be randomized to
      undergo OCT-guided angioplasty (use of OCT to optimize procedural result,
      including change to strategy with the possibility of additional interventions) or
      angioplasty under fluoroscopy alone. The primary end point is the functional
      result of the angioplasty procedure as assessed by fractional flow reserve (FFR)
      measured at the end of the procedure. Secondary end points include safety of OCT
      in the context of angioplasty for ACS, percentage of patients in whom OCT reveals
      suboptimal result of stenting, percentage of patients in whom a change in
      procedural strategy is decided based on OCT data, correlation between
      quantitative measures by OCT and FFR, determination of a threshold for
      quantitative OCT measure that best predicts FFR >= 0.90, and identification of
      OCT variables that predict postprocedure FFR. Adverse cardiac events (death,
      recurrent myocardial infarction, stent thrombosis, and repeat target lesion
      revascularization) at 6 months will be recorded. CONCLUSION: The DOCTORS
      randomized trial (ClinicalTrials.gov NCT01743274) is designed to investigate
      whether use of OCT yields useful additional information beyond that obtained by
      angiography alone and, if so, whether this information changes physician strategy
      and impacts on the functional result of angioplasty as assessed by FFR.

PMID- 25066557
TI  - Association of metabolic syndrome and its individual components with outcomes
      among patients with high-risk non-ST-segment elevation acute coronary syndromes.
AB  - BACKGROUND: The relationship of metabolic syndrome and its individual components
      (obesity, hypertension, glucose intolerance, high triglycerides, and low high
      density lipoprotein cholesterol) with 1-year mortality in non-ST-segment
      elevation acute coronary syndromes (NSTE ACS) patients is not known. METHODS: The
      association of metabolic syndrome (and its individual components) with all-cause
      mortality within 1 year was assessed in NSTE ACS patients enrolled in the EARLY
      ACS trial. Adjusted hazard ratio (HR) and 95% CIs are reported. RESULTS: Of 9,406
      patients, 2,596 (27.6%) had metabolic syndrome. Compared with those without
      metabolic syndrome, patients with this syndrome were younger, were more often
      female, and had a higher prevalence of comorbid conditions and higher-risk
      presenting features. Metabolic syndrome was not associated with increased 1-year
      mortality (HR 1.20, 95% CI 0.97-1.47; P = .09). The risk of 1-year mortality
      varied across the individual components: high-density lipoprotein <40 mg/dL
      (men)/<50 mg/dL (women; or dyslipidemia) was associated with higher risk (HR
      1.52, 95% CI 1.15-2.02), and triglycerides >150 mg/dL (or dyslipidemia) was
      associated with lower risk (HR 0.66, 95% CI 0.54-0.81), whereas the other
      components (ie, body mass index >30 kg/m(2), fasting plasma glucose >100 mg/dL or
      diabetes, systolic blood pressure >130 mm Hg or diastolic >85 mm Hg [or
      hypertension]) were associated with neutral risk of this event. CONCLUSIONS: The
      individual components of metabolic syndrome had varying associations with 1-year
      mortality, and as an integrated diagnosis, metabolic syndrome was not
      significantly associated with 1-year mortality. Thus, patient case-mix of the
      studied NSTE ACS population may influence the observed relationship of metabolic
      syndrome with subsequent cardiovascular events.

PMID- 25066558
TI  - Long-term outcomes associated with hospital acquired thrombocytopenia among
      patients with non-ST-segment elevation acute coronary syndrome.
AB  - BACKGROUND: Acquired thrombocytopenia after a non-ST-segment-elevation-acute
      coronary syndrome (NSTE-ACS) has been associated with increased in-hospital
      mortality and hemorrhagic complications, but longer term outcomes are unclear. We
      examined the association between thrombocytopenia and long-term outcomes after
      accounting for thrombocytopenia severity and discharge medication use. METHODS:
      Data from 7,435 NSTE-ACS patients enrolled in the SYNERGY trial were analyzed.
      Severe thrombocytopenia was defined as a nadir platelet count <100 * 10(9)/L or a
      >= 50% drop from baseline. Mild thrombocytopenia was defined as a nadir platelet
      count between 100 and 149 * 10(9)/L with a <50% drop from baseline. The primary
      outcomes of interest were in-hospital GUSTO moderate-severe bleeding and 1-year
      mortality. RESULTS: Overall, 675 patients (9.1%) developed mild thrombocytopenia
      and 139 patients (1.9%) developed severe thrombocytopenia. In-hospital bleeding
      risks were higher in patients with mild (7.7%, adjusted HR 1.63, 95% CI 1.16
      2.29) or severe (28.2%, adjusted HR 6.93, 95% CI 4.55-10.56) thrombocytopenia
      than in patients without thrombocytopenia (5.2%). One-year mortality rates were
      6.5%, 8.1%, and 28.1% among patients with no, mild, and severe thrombocytopenia,
      respectively (log rank P < 0.001) but only severe thrombocytopenia remained
      significantly associated with increased mortality after adjustment: HR 4.07, 95%
      CI 2.86-5.78. Patients who developed severe thrombocytopenia were less likely to
      be discharged on guideline-recommended antiplatelet therapy. The relationship
      between severe thrombocytopenia and mortality was attenuated by but persisted
      after adjusting for discharge medication use (HR 2.83, 95% CI 1.49-5.38).
      CONCLUSIONS: Thrombocytopenia occurs commonly during the course of NSTE-ACS care;
      even mild decreases are associated with clinically meaningful bleeding. Patients
      who developed severe thrombocytopenia were less likely to be discharged on
      guideline-recommended antiplatelet therapy; this may contribute to their higher
      associated long-term mortality.

PMID- 25066559
TI  - Agreement between public register and adjudication committee outcome in a
      cardiovascular randomized clinical trial.
AB  - The objective of this study is to describe the agreement between randomized trial
      outcome assessment by committee and outcomes entirely identified through public
      registers. METHODS: In the CLARICOR trial, 4,372 patients with stable coronary
      heart disease received a short course of clarithromycin versus placebo and were
      followed up for 2.6 years. The pertinent hospital records and death certificates
      had originally been evaluated by the adjudication committee using common
      definitions of outcomes mapped into a 6-category list. We now mechanically
      converted the International Classification of Diseases-coded diagnoses of the
      public registries into the same categories. After cross-tabulation of the
      committee diagnoses with National Patient Register diagnoses and Register of
      Causes of Death, we calculate agreement and compare the estimated intervention
      effects of the 2 data sets. RESULTS: With public register data, the protocol
      specified categories were slightly more frequent. Overall agreement was 74% for
      hospital discharges and 60% for cause of death, but the intervention effect,
      expressed as a hazard ratio, stayed within 4% of the value originally obtained
      with the adjudication committee (P >= .35). CONCLUSIONS: Our results show a
      modest agreement between formal adjudication and outcomes deducible from public
      registers. However, the estimated intervention effect did not differ noticeably
      between the 2 data sources. If studies on a wide range of public registers
      confirm these findings, register outcomes may be considered as a replacement for
      adjudication committees.

PMID- 25066560
TI  - Evaluating cardiovascular event reduction with ezetimibe as an adjunct to
      simvastatin in 18,144 patients after acute coronary syndromes: final baseline
      characteristics of the IMPROVE-IT study population.
AB  - BACKGROUND: The IMProved Reduction of Outcomes: Vytorin Efficacy International
      Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major
      cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40
      mg/d of simvastatin therapy in patients who present with acute coronary syndromes
      and have low-density lipoprotein cholesterol (LDL-C) <= 125 mg/dL. METHODS: The
      primary composite end point is CV death, nonfatal myocardial infarction (MI),
      nonfatal stroke, rehospitalization for unstable angina (UA), and coronary
      revascularization (>= 30 days postrandomization). The simvastatin monotherapy
      arm's LDL-C target is <70 mg/dL. Ezetimibe was assumed to further lower LDL-C by
      15 mg/dL and produce an estimated ~8% to 9% treatment effect. The targeted number
      of events is 5,250. RESULTS: We enrolled 18,144 patients with either ST-segment
      elevation MI (STEMI, n = 5,192) or UA/non-ST-segment elevation MI (UA/NSTEMI, n =
      12,952) from October 2005 to July 2010. Western Europe (40%) and North America
      (38%) were the leading enrolling regions. The STEMI cohort was younger and had a
      higher percentage of patients naive to lipid-lowering treatment compared with the
      UA/NSTEMI cohort. The UA/NSTEMI group had a higher prevalence of diabetes,
      hypertension, and prior MI. Median LDL-C at entry was 100 mg/dL for STEMI and 93
      mg/dL for UA/NSTEMI patients. CONCLUSIONS: This trial is evaluating LDL-C
      lowering beyond previously targeted LDL-C levels. The results depend on achieving
      the desired separation of LDL-C with ezetimibe and on the assumption that
      ezetimibe's lowering of LDL-C will have similar event reduction efficacy as the
      LDL-C lowering from a statin. The results could affect future therapies and
      guidelines.

PMID- 25066561
TI  - Prevalence, characteristics, and predictors of early termination of
      cardiovascular clinical trials due to low recruitment: insights from the
      ClinicalTrials.gov registry.
AB  - BACKGROUND: Early termination of clinical trials due to low recruitment
      represents an understudied challenge for clinical research. We aimed to describe
      characteristics of cardiovascular trials terminated because of low recruitment
      and identify the major predictors of such early termination. METHODS: We reviewed
      all cardiovascular clinical trials (7,042 studies) registered in
      ClinicalTrials.gov from February 29, 2000, to January 17, 2013, and assessed
      information about trials that were completed and those that were terminated
      early. Logistic regression models were developed to identify independent
      predictors of early termination due to low recruitment. RESULTS: Our search
      strategy identified 6,279 cardiovascular clinical trials, of which 684 (10.9%)
      were terminated prematurely. Of these halted trials, the main reason for
      termination was lower than expected recruitment (278 trials; 53.6%). When
      comparing trials that terminated early because of low recruitment with those that
      were completed, we found that studies funded by the National Institutes of Health
      or other US federal agencies (odds ratio [OR] 0.35, 95% confidence interval [CI]
      0.14-0.89), studies of behavior/diet intervention (OR 0.35, 95% CI 0.19-0.65),
      and single-arm design studies (OR 0.57, 95% CI 0.42-0.78) were associated with a
      lower risk of early termination. University/hospital-funded (OR 1.52, 95% CI 1.10
      2.10) and mixed-source-funded studies (OR 2.14, 95% CI 1.52-3.01) were associated
      with a higher likelihood of early termination due to lower than expected
      recruitment rates. CONCLUSIONS: Low recruitment represents the main cause of
      early termination of cardiovascular clinical trials. Funding source, type of
      intervention, and study design are factors associated with early termination due
      to low recruitment and might be good targets for improving enrollment into
      cardiovascular clinical trials.

PMID- 25066562
TI  - Is there a role for diastolic function assessment in era of delayed enhancement
      cardiac magnetic resonance imaging?: a multimodality imaging study in patients
      with advanced ischemic cardiomyopathy.
AB  - Cardiac magnetic resonance (CMR) identifies important prognostic variables in
      ischemic cardiomyopathy (ICM) patients such as left ventricular (LV) volumes, LV
      ejection fraction (LVEF), peri-infarct zone, and myocardial scar burden (MSB). It
      is unknown whether Doppler-based diastolic dysfunction (DDF) retains its
      prognostic value in ICM patients, in the context of current imaging, medical, and
      device therapies. METHODS: Diastolic function was evaluated in ICM patients (LVEF
      <= 40% and >= 70% stenosis in >= 1 coronary artery) who underwent transthoracic
      echocardiogram and delayed hyperenhancement CMR studies within 7 days. The
      association of DDF with the combined end point was assessed after risk-adjustment
      using Cox proportional hazards models. RESULTS: A total of 360 patients with
      severe LV dysfunction (LVEF = 24 +/- 9%) and extensive MSB (31 +/- 17%) were
      evaluated; DDF was present in all patients (stage 1%-44%, stage 2%-25%, stage 3%
      31%). There were 130 events (124 deaths and 6 heart transplants) over a median
      follow-up of 5.8 years (IQR, 3.7-7.4 years). On multivariable analysis, DDF >
      stage 1 (HR, 1.37; P = .007) was associated with the combined end-point,
      independent of clinical risk score (HR, 2.40; P < .0001), implantable
      cardioverter defibrillator implantation (HR, 0.60; P = .009), incomplete
      revascularization (HR, 1.32; P = .003), mitral regurgitation (HR, 3.37; P = .01),
      peri-infarct zone area (HR, 1.04; P = 0.02), and MSB (HR, 1.02; P = .01). DDF had
      incremental prognostic value for the combined end-point (model chi(2) increased
      from 89 to 95, P = .02). CONCLUSION: DDF is a powerful predictor of mortality in
      ICM patients with significant LV dysfunction, independent of clinical and CMR
      data. DDF assessment provides incremental value, improving risk stratification.

PMID- 25066563
TI  - Role of simultaneous carotid ultrasound in patients undergoing stress
      echocardiography for assessment of chest pain with no previous history of
      coronary artery disease.
AB  - BACKGROUND: We prospectively explored prevalence of carotid disease (CD), its
      independent association with coronary artery disease (CAD) and outcome as well as
      potential impact on management, in patients undergoing stress echocardiography
      (SE) for new onset chest pain without known CAD. METHODS: Accordingly, 591
      consecutive patients referred for SE underwent carotid ultrasound. Carotid
      disease was defined as carotid intima-media thickness (C-IMT) >75th percentile
      for age and sex and/or presence of plaque. RESULTS: Myocardial ischemia was
      demonstrated in only a minority (11%), but there was a high prevalence of CD
      (70%). Incidence of CD was similar in patients with and without ischemia (76%
      versus 69%, P = .26). Carotid data led to reclassification of Framingham risk
      score categories in 65% of patients as well as more than a third of negative SE
      patients potentially benefitting from primary prevention therapy. Of the 83
      patients undergoing coronary arteriography, 59 (71%) demonstrated coronary
      atherosclerosis (any atheroma) and 33 (40%) CAD. Positive predictive value of SE
      for CAD was 56%, but presence of carotid plaque improved it to 70%. Although both
      CD and plaque showed association with CAD and revascularization, after adjustment
      for conventional risk factors, only carotid plaque maintained significant
      association (P = .024 and P = .023, respectively). CONCLUSIONS: There is
      significantly higher prevalence of CD compared with myocardial ischemia in
      patients undergoing SE and carotid ultrasound for suspected CAD. This can lead to
      significant Framingham risk score reclassification with important primary
      prevention implications. Carotid plaque is superior to clinical assessment for
      the prediction of CAD and improves positive predictive value of SE for CAD in
      these patients.

PMID- 25066564
TI  - Pre-percutaneous coronary intervention statin therapy: is it necessary?

PMID- 25066565
TI  - Reply to: Prepercutaneous coronary interventions statin therapy: is it necessary?

PMID- 25066566
TI  - Interarm blood pressure differences should also be recorded.

PMID- 25066567
TI  - The EARNEST study: interarm blood pressure differences should also be recorded.

PMID- 25066568
TI  - Intrahepatic multicystic biliary hamartoma: Presentation of a case report.

PMID- 25066569
TI  - Gastrojejunal anastomotic stenosis after laparoscopic gastric bypass. Experience
      in 280 cases in 8 years.
AB  - OBJECTIVE: Gastrojejunal stricture (GYS), not only is a common complication after
      laparoscopic gastric bypass, but its frequency is about 15% according to
      bibliography. Our aim is to present our experience after 280 laparoscopic gastric
      bypass. PATIENTS AND METHOD: From January 2004 to December 2012, 280 patients
      underwent a laparoscopic Roux en Y gastric bypass with creation of the
      gastrojejunal anastomosis is performed with circular stapler type CEAA No 21 in
      265 patients and with a linear stapler in 15 patients. In all patients with
      persistent feeding intolerance were performed barium transit and/or gastroscopy.
      When gastrojejunal stricture showed proceeded to endoscopic pneumatic dilation.
      RESULTS: Twenty cases (7.1%) developed a gastrojejunal stricture, in 4 of these
      cases the initial diagnosis was made by barium transit and all case were
      confirmed by endoscopy. Five patients had a history of digestive bleeding that
      required endoscopic sclerosis of the bleeding lesion. All cases were resolved by
      endoscopic dilatation. One patient suffered a perforation and a re-intervention.
      At follow-up has not been detected re-stricture. CONCLUSION: Structure at the
      gastrojejunal anastomosis after gastric bypass is the commonest complication
      early after surgery. Endoscopic balloon dilatation is a safe and effective
      therapy.

PMID- 25066570
TI  - Autoimmune pancreatitis: a surgical dilemma.
AB  - Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis
      that often manifests as obstructive jaundice associated with a pancreatic mass or
      an obstructive bile duct lesion, and that has an excellent response to
      corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is
      considered as a rare entity. The clinical and radiological presentation of AIP
      can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and
      obliging the surgeon to balance decision-making between the potential risk
      presented by the misdiagnosis of a deadly disease against the desire to avoid
      unnecessary major surgery for a disease that responds effectively to
      corticosteroid treatment. In this review we detail the current and critical
      points for the diagnosis, classification and treatment for AIP, with a special
      emphasis on surgical series and the methods to differentiate between this
      pathology and bilio-pancreatic cancer. 

PMID- 25066571
TI  - Hepatic inflammatory pseudotumor: a difficult preoperative diagnosis in an
      oncological patient.

PMID- 25066572
TI  - Rupture of an aneurysm of the middle colic artery.

PMID- 25066573
TI  - Incomplete surgery for bronchial cystic adenoid carcinoma: A therapeutic
      alternative.

PMID- 25066574
TI  - Portal vein thrombosis associated with right hepatic artery injury during
      cholecystectomy: an uncommon indication for urgent liver transplantation.

PMID- 25066575
TI  - Functionalization of remote C-H bonds: expanding the frontier.
AB  - Novel tool set: New methodologies for the functionalization of remote C?H bonds
      have been developed recently. In diverse approaches high selectivities are
      achieved for the functionalization of less reactive C(sp(2) )?H as well as
      C(sp(3) )?H bonds distal to any substituents. 

PMID- 25066576
TI  - Learning from a public health hero: what would Ciro do now?

PMID- 25066577
TI  - The Federation's pages. Planetary health and the World Federation of Public
      Health Associations.

PMID- 25066579
TI  - Sensitivity of TATP to a TASER electrical output.
AB  - A series of experiments were performed to evaluate and document the effect of a
      TASER ("stun gun") on triacetone triperoxide (TATP), an easily manufactured
      explosive used often in IEDs and suicide bombing vests. TATP samples were
      synthesized and subjected to several tests of their sensitivity. These samples
      were run through a BAM Friction test with a result of <0.5 N, Impact Test with a
      result of 5.8 +/- 0.4 cm, and Electrostatic Discharge test with a result of 0.073
      +/- 0.018 J. In addition, TATP was shocked with a TASER in a variety of
      configurations. The TATP reacted in 17/17 tests when the TASER arced through the
      TATP and 0/4 times when the TATP was configured in such a way that the TATP was
      not subjected to the electrical arc. Based on the experimental data, TATP will
      readily explode in a variety of configurations by a TASER or similar device.
      Testing should be expanded, as the data presented here are limited to a single
      formulation of TATP. Just one of a large array of TASER-like devices by a single
      manufacturer were tested; other devices, scenarios and formulations of TATP and
      other likely threat materials should be assessed. 

PMID- 25066578
TI  - Identification of peptidases in highly pathogenic vs. weakly pathogenic Naegleria
      fowleri amebae.
AB  - Naegleria fowleri, a free-living ameba, is the causative agent of Primary Amebic
      Meningoencephalitis. Highly pathogenic mouse-passaged amebae (Mp) and weakly
      pathogenic axenically grown (Ax) N. fowleri were examined for peptidase activity.
      Zymography and azocasein peptidase activity assays demonstrated that Mp and Ax N.
      fowleri exhibited a similar peptidase pattern. Prominent for whole cell lysates,
      membranes and conditioned medium (CM) from Mp and Ax amebae was the presence of
      an activity band of approximately 58 kDa that was sensitive to E64, a cysteine
      peptidase inhibitor. However, axenically grown N. fowleri demonstrated a high
      level of this peptidase activity in membrane preparations. The inhibitor E64 also
      reduced peptidase activity in ameba-CM consistent with the presence of secreted
      cysteine peptidases. Exposure of Mp amebae to E64 reduced their migration through
      matrigel that was used as an extracellular matrix, suggesting a role for cysteine
      peptidases in invasion of the central nervous system (CNS). The collective
      results suggest that the profile of peptidases is not a discriminative marker for
      distinguishing Mp from Ax N. fowleri. However, the presence of a prominent level
      of activity for cysteine peptidases in N. fowleri membranes and CM, suggests that
      these enzymes may serve to facilitate passage of the amebae into the CNS. 

PMID- 25066580
TI  - "That's who I am: a fat person in a thin body": weight loss, negative self
      evaluation, and mitigating strategies following weight loss surgery.
AB  - OBJECTIVE: To explore negative self-evaluation following weight loss surgery
      (WLS). METHODS: In-depth interviews were conducted with 11 women who had WLS.
      Thematic analysis was conducted through an iterative process, allowing categories
      and themes to emerge. To ensure rigor, two coders analyzed the data. Data were
      collected until thematic saturation was achieved. RESULTS: All participants
      reported health as the motivation for WLS. Overall sentiment regarding WLS was
      positive. However, negative self-evaluation was reported and includes the
      following: (a) body-image distortion; (b) body-image dissatisfaction, including
      excessive skin; and (c) perceived stigma. Mitigating strategies include the
      following: (a) utilizing markers of progress to increase assimilation of a new
      identity as a thinner person, and (b) reflecting on the former self as a time of
      decreased quality of life. IMPLICATIONS FOR PRACTICE: Nurse practitioners and
      other clinicians treat and counsel patients on obesity and obesity-related
      morbidity, and may need to discuss WLS with patients who are either contemplating
      it or have already undergone it. The findings from the present study can provide
      clinicians insight into the possible psychological effects of WLS-associated
      weight loss. Bringing possible negative self-evaluative effects into open
      discussion can help optimize patient care and healthcare results.

PMID- 25066581
TI  - Arterial pulsatility improvement in a feedback-controlled continuous flow left
      ventricular assist device: an ex-vivo experimental study.
AB  - Continuous flow left ventricular assist devices (CF-LVADs) reduce arterial
      pulsatility, which may cause long-term complications in the cardiovascular
      system. The aim of this study is to improve the pulsatility by driving a CF-LVAD
      at a varying speed, synchronous with the cardiac cycle in an ex-vivo experiment.
      A Micromed DeBakey pump was used as CF-LVAD. The heart was paced at 140 bpm to
      obtain a constant cardiac cycle for each heartbeat. First, the CF-LVAD was
      operated at a constant speed. At varying-speed CF-LVAD assistance, the pump was
      driven such that the same mean pump output was generated. For synchronization
      purposes, an algorithm was developed to trigger the CF-LVAD each heartbeat. The
      pump flow rate was selected as the control variable and a reference model was
      used for regulating the CF-LVAD speed. Continuous and varying-speed CF-LVAD
      assistance provided the same mean arterial pressure and flow rate, while the
      index of pulsatility doubled in both arterial pressure and pump flow rate signals
      under pulsatile pump speed support. This study shows the possibility of improving
      the pulsatility in CF-LVAD support by regulating pump speed over a cardiac cycle
      without compromising the overall level of support.

PMID- 25066582
TI  - Changes in dissipated energy and contact pressure after osteochondral graft
      transplantation.
AB  - Osteochondral autologous transplantation is frequently used to repair small
      cartilage defects. Incongruence between the osteochondral graft surface and the
      adjacent cartilage leads to changed friction and contact pressure. The present
      study wanted to analyze the differences between intact and surgically treated
      cartilage surface in respect to contact pressure and frictional characteristic
      (dissipated energy). Six ovine carpometacarpal joints were used in the present
      study. Dissipated energy during instrumentally controlled joint movement as well
      as static contact pressure were measured in different cartilage states (intact,
      defect, deep-, flush-, high-implanted osteochondral graft and cartilage failure
      simulation on a high-implanted graft). The best contact area restoration was
      observed after the flush implantation. However, the dissipated energy
      measurements did not reveal an advantage of the flush implantation compared to
      the defect and deep-implanted graft states. The high-implanted graft was
      associated with a significant increase of the mean contact pressure and decrease
      of the contact area but the dissipated energy was on the level of intact
      cartilage in contrast to other treatments where the dissipated energy was
      significantly higher as in the intact state. However the cartilage failure
      simulation on the high-implanted graft showed the highest increase of the
      dissipated energy. 

PMID- 25066583
TI  - An in vitro investigation of the influence of stenosis severity on the flow in
      the ascending aorta.
AB  - Cardiovascular diseases can lead to abnormal blood flows, some of which are
      linked to hemolysis and thrombus formation. Abnormal turbulent flows of blood in
      the vessels with stenosis create strong shear stresses on blood elements and may
      cause blood cell destruction or platelet activation. We implemented a Lagrangian
      (following the fluid elements) measurement technique of three dimensional
      particle tracking velocimetry that provides insight on the evolution of viscous
      and turbulent stresses along blood element trajectories. We apply this method to
      study a pulsatile flow in a compliant phantom of an aorta and compare the results
      in three cases: the reference case (called "healthy" case), and two cases of
      abnormal flows due to mild and severe stenosis, respectively. The chosen
      conditions can mimic a clinical application of an abnormal flow due to a calcific
      valve. We estimate the effect of aortic stenosis on the kinetic energy of the
      mean flow and the turbulent kinetic energy, which increases about two orders of
      magnitude as compared with the healthy flow case. Measuring the total flow stress
      acting on a moving fluid element that incorporates viscous stresses and the
      apparent turbulent-induced stresses (the so-called Reynolds stresses) we find out
      similar increase of the stresses with the increased severity of the stenosis.
      Furthermore, these unique Lagrangian measurements provide full acceleration and,
      consequently, the forces acting on the blood elements that are estimated to reach
      the level that can considerably deform red blood cells. These forces are strong
      and abrupt due to the contribution of the turbulent fluctuations which is much
      stronger than the typically measured phase-averaged values. 

PMID- 25066584
TI  - A neural network approach for determining gait modifications to reduce the
      contact force in knee joint implant.
AB  - There is a growing interest in non-surgical gait rehabilitation treatments to
      reduce the loading in the knee joint. In particular, synergetic kinematic changes
      required for joint offloading should be determined individually for each subject.
      Previous studies for gait rehabilitation designs are typically relied on a "trial
      and-error" approach, using multi-body dynamic (MBD) analysis. However MBD is
      fairly time demanding which prevents it to be used iteratively for each subject.
      This study employed an artificial neural network to develop a cost-effective
      computational framework for designing gait rehabilitation patterns. A feed
      forward artificial neural network (FFANN) was trained based on a number of
      experimental gait trials obtained from literature. The trained network was then
      hired to calculate the appropriate kinematic waveforms (output) needed to achieve
      desired knee joint loading patterns (input). An auxiliary neural network was also
      developed to update the ground reaction force and moment profiles with respect to
      the predicted kinematic waveforms. The feasibility and efficiency of the
      predicted kinematic patterns were then evaluated through MBD analysis. Results
      showed that FFANN-based predicted kinematics could effectively decrease the total
      knee joint reaction forces. Peak values of the resultant knee joint forces, with
      respect to the bodyweight (BW), were reduced by 20% BW and 25% BW in the
      midstance and the terminal stance phases. Impulse values of the knee joint
      loading patterns were also decreased by 17% BW*s and 24%BW*s in the corresponding
      phases. The FFANN-based framework suggested a cost-effective forward solution
      which directly calculated the kinematic variations needed to implement a given
      desired knee joint loading pattern. It is therefore expected that this approach
      provides potential advantages and further insights into knee rehabilitation
      designs.

PMID- 25066585
TI  - Synthesis, dual-nonlinear magnetic resonance and microwave absorption properties
      of nanosheet hierarchical cobalt particles.
AB  - In this paper, we report the synthesis of three kinds of novel nanosheet
      hierarchical cobalt particles by adjusting the [C4H4O6](2-)/Co(2+) ratio through
      a liquid reduction method. We investigated the electromagnetic properties of the
      cobalt particles in detail over the microwave frequency range of 1-18 GHz. The
      results show that the real part of the permittivity decreases and the imaginary
      part of the permeability increases with an increase in the [C4H4O6](2-)/Co(2+)
      ratio. The permeability displays two resonance peaks over the frequency range.
      The cobalt particles with [C4H4O6](2-)/Co(2+) = 6 have a maximum reflection loss
      of -48.03 dB at 13.61 GHz, and the effective absorption bandwidth (RL <= -10 dB)
      is 6.76 GHz corresponding to a thickness of 1.7 mm. Considering the impedance
      matching and attenuation based on the electromagnetic parameters, we designed a
      way to obtain cobalt particles with excellent microwave absorption properties by
      decreasing the real part of permittivity and increasing the imaginary part of
      permeability. 

PMID- 25066587
TI  - Cancer prevention from a psychosocial oncology perspective.

PMID- 25066586
TI  - Body image screening for cancer patients undergoing reconstructive surgery.
AB  - OBJECTIVES: Body image is a critical issue for cancer patients undergoing
      reconstructive surgery, as they can experience disfigurement and functional
      impairment. Distress related to appearance changes can lead to various
      psychosocial difficulties, and patients are often reluctant to discuss these
      issues with their healthcare team. Our goals were to design and evaluate a
      screening tool to aid providers in identifying patients who may benefit from
      referral for specialized psychosocial care to treat body image concerns. METHODS:
      We designed a brief four-item instrument and administered it at a single time
      point to cancer patients who were undergoing reconstructive treatment. We used
      simple and multinomial regression models to evaluate whether survey responses,
      demographic, or clinical variables predicted interest and enrollment in
      counseling. RESULTS: Over 95% of the sample (n = 248) endorsed some concerns,
      preoccupation, or avoidance because of appearance changes. Approximately one
      third of patients were interested in obtaining counseling or additional
      information to assist with body image distress. Each survey item significantly
      predicted interest and enrollment in counseling. Concern about future appearance
      changes was the single best predictor of counseling enrollment. Sex, age, and
      cancer type were not predictive of counseling interest or enrollment.
      CONCLUSIONS: We present initial data supporting use of the Body Image Screener
      for Cancer Reconstruction. Our findings suggest benefits of administering this
      tool to patients presenting for reconstructive surgery. It is argued that
      screening and treatment for body image distress should be provided to this
      patient population at the earliest possible time point.

PMID- 25066589
TI  - Differential Behavior of Fibroblasts and Epithelial Cells on Structured Implant
      Abutment Materials: A Comparison of Materials and Surface Topographies.
AB  - PURPOSE: The aim of this study was to compare the proliferation and attachment
      behavior of fibroblasts and epithelial cells on differently structured abutment
      materials. MATERIALS AND METHODS: Three different surface topographies were
      prepared on zirconia and titanium alloy specimens and defined as follows:
      machined (as delivered without further surface modification), smooth (polished),
      and rough (sandblasted). Energy-dispersive X-ray spectroscopy, topographical
      analysis, and water contact angle measurements were used to analyze the surface
      properties. Fibroblasts (HGF1) and epithelial cells (HNEpC) grown on the
      specimens were investigated 24 hours and 72 hours after seeding and counted using
      fluorescence imaging. To investigate adhesion, the abundance and arrangement of
      the focal adhesion protein vinculin were evaluated by immunocytochemistry.
      RESULTS: Similar surface topographies were created on both materials. Fibroblasts
      exhibited significant higher proliferation rates on comparable surface
      topographies of zirconia compared with the titanium alloy. The proliferation of
      fibroblasts and epithelial cells was optimal on different substrate/topography
      combinations. Cell spreading was generally higher on polished and machined
      surfaces than on sandblasted surfaces. Rough surfaces provided favorable
      properties in terms of cellular adhesion of fibroblasts but not of epithelial
      cells. CONCLUSIONS: Our data support complex soft tissue cell-substrate
      interactions: the fibroblast and epithelial cell response is influenced by both
      the material and surface topography.

PMID- 25066590
TI  - Assessing medical students' knowledge of IR at two American medical schools.
AB  - PURPOSE: To determine if there was a difference in the level of knowledge about
      interventional radiology (IR) between medical students in preclinical years of
      training compared with medical students in clinical years of training at two
      medical schools and to compare awareness of IR based on the curriculum at each
      school: one with required radiology education and one without such a requirement.
      MATERIALS AND METHODS: An anonymous survey was distributed to students at two
      medical schools; the survey assessed knowledge of IR, knowledge of training
      pathways, and preferred methods to increase exposure. Responses of the
      preclinical and clinical groups were compared, and responses from the clinical
      groups at each school were compared. RESULTS: "Poor" or "fair" knowledge of IR
      was reported by 84% (n = 217 of 259) of preclinical students compared with 62% of
      clinical students (n = 110 of 177; P < .001). IR was being considered as a career
      by 11% of all students (15%, n = 40 of 259 preclinical; 5%, n = 9 of 177
      clinical). The main reason respondents were not considering IR was "lack of
      knowledge" (65%, n = 136 of 210 preclinical; 20%, n = 32 of 162 clinical).
      Students in the clinical group at the institution with a required radiology
      rotation reported significantly better knowledge of IR than clinical students
      from the institution without a required clerkship (P = .017). CONCLUSIONS: There
      are significant differences in knowledge of IR between preclinical and clinical
      students. Required radiology education in the clinical years does increase
      awareness of IR.

PMID- 25066591
TI  - Aortic arch vessel geometries and deformations in patients with thoracic aortic
      aneurysms and dissections.
AB  - PURPOSE: To quantify aortic arch geometry and in vivo cardiac-induced and
      respiratory-induced arch translations and arch branch angulations using three
      dimensional geometric modeling techniques. MATERIALS AND METHODS: Scanning with
      electrocardiogram-gated computed tomography angiography during inspiratory and
      expiratory breath holds was performed in 15 patients (age, 64 y +/- 14) with
      thoracic aortic aneurysms or dissections. From the lumen models, centerlines of
      the thoracic aorta, brachiocephalic artery, left common carotid artery, and left
      subclavian artery and their branching ostia positions were quantified. Three
      dimensional translation of vessel ostia, branching angles, and their changes
      secondary to cardiac pulsation and respiration were computed. RESULTS: During
      expiration, all ostia translated rightward from systole to diastole (P < .035).
      Regardless of cardiac phase, all ostia translated posteriorly and superiorly from
      inspiration to expiration (P < .05). Respiration induced greater posterior and
      superior translations than cardiac pulsation (P < .03). The left common carotid
      artery branch angled significantly more toward the aortic arch compared with the
      brachiocephalic artery and left subclavian artery (P < .03). No significant
      changes in branching angle were found from systole to diastole or inspiration to
      expiration. CONCLUSIONS: In patients with thoracic aortic aneurysms or
      dissections, the thoracic aortic arch translated significantly secondary to
      inspiration and expiration and to a lesser extent secondary to cardiac pulsation.
      Insignificant branching angle changes suggest that the aortic arch and its branch
      origins move predominantly in unison.

PMID- 25066593
TI  - Modulation of magnetic properties at room temperature: coordination-induced
      valence tautomerism in a cobalt dioxolene complex.
AB  - The valence-tautomeric six-coordinate complex [Co(tbdiox)2(4-papy)2] (1; tbdiox =
      redox-active 3,5-di-tert-butyl-o-dioxolene, 4-papy = 4-phenylazopyridine) was
      synthesized and its electronic structure examined. Whereas 1 shows regular
      thermally driven valence tautomerism in the solid state, it partially dissociates
      in solution to form the five-coordinate species [Co(tbdiox)2(4-papy)] (2) and
      free 4-papy. Species 1 and 2 exhibit different electronic structures-low-spin
      (ls) Co(III) and high-spin (hs) Co(II), respectively-in solution at room
      temperature and therefore different magnetic properties. Since 1 and 2 are in an
      equilibrium that is 4-papy-dependent, the magnetic moment of the solution species
      can be tuned by means of the ligand content. Thus, the concept of coordination
      induced valence tautomerism (CIVT) has been introduced. The electronic structures
      of 1 and 2 as well as their CIVT were elucidated by X-ray crystallography,
      electrochemistry, titration experiments, and all variable-temperature SQUID
      susceptometry, NMR, EPR, and electronic absorption spectroscopy. The experimental
      findings are strongly supported by broken-symmetry DFT calculations. The magnetic
      exchange interactions in different types of valence-tautomeric cobalt complexes
      were explored computationally.

PMID- 25066592
TI  - Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by
      hemagglutination inhibition and virus microneutralization assays in a cohort of
      seroconverting adults in Singapore.
AB  - BACKGROUND: The rate of decline of antibody titers to influenza following
      infection can affect results of serological surveys, and may explain re-infection
      and recurrent epidemics by the same strain. METHODS: We followed up a cohort who
      seroconverted on hemagglutination inhibition (HI) antibody titers (>= 4-fold
      increase) to pandemic influenza A(H1N1)pdm09 during a seroincidence study in
      2009. Along with the pre-epidemic sample, and the sample from 2009 with the
      highest HI titer between August and October 2009 (A), two additional blood
      samples obtained in April 2010 and September 2010 (B and C) were assayed for
      antibodies to A(H1N1)pdm09 by both HI and virus microneutralization (MN) assays.
      We analyzed pair-wise mean-fold change in titers and the proportion with HI
      titers >= 40 and MN >= 160 (which correlated with a HI titer of 40 in our assays)
      at the 3 time-points following seroconversion. RESULTS: A total of 67
      participants contributed 3 samples each. From the highest HI titer in 2009 to the
      last sample in 2010, 2 participants showed increase in titers (by HI and MN),
      while 63 (94%) and 49 (73%) had reduction in HI and MN titers, respectively.
      Titers by both assays decreased significantly; while 70.8% and 72.3% of subjects
      had titers of >= 40 and 160 by HI and MN in 2009, these percentages decreased to
      13.9% and 36.9% by September 2010. In 6 participants aged 55 years and older, the
      decrease was significantly greater than in those aged below 55, so that none of
      the elderly had HI titers >= 40 nor MN titers >= 160 by the final sample. Due to
      this decline in titers, only 23 (35%) of the 65 participants who seroconverted on
      HI in sample A were found to seroconvert between the pre-epidemic sample and
      sample C, compared to 53 (90%) of the 59 who seroconverted on MN on Sample A.
      CONCLUSIONS: We observed marked reduction in titers 1 year after seroconversion
      by HI, and to a lesser extent by MN. Our findings have implications for re
      infections, recurrent epidemics, vaccination strategies, and for cohort studies
      measuring infection rates by seroconversion.

PMID- 25066594
TI  - [Viral respiratory tract infections in the Neonatal Intensive Care Unit].
AB  - INTRODUCTION: Viral respiratory infections cause major morbidity and mortality in
      preterm infants. We have performed a prospective study in our neonatal intensive
      care unit (NICU) to determine the incidence of respiratory infections, their
      impact and the epidemiology and outcome in high risk neonates. PATIENTS AND
      METHODS: From September 2011 to May 2013 a prospective study was conducted in all
      preterm infants < 32 weeks gestational age and in all term newborns admitted to
      NICU for any pathology that are anticipated to have an income exceeding two
      weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and
      weekly until discharge for virologic study with polymerase chain reaction. When
      these babies presented respiratory symptoms a new NPA was collected in this
      moment. A clinical form was filled by the physician. RESULTS: A total of 60
      infants were analyzed: 30 (50%) had a gestational age < 32 weeks and 36 (60%)
      weighing less than 1500 grams. We collected a total of 256 nasopharyngeal
      aspirate samples, 24 of them being positive (9.3%). These 24 positive samples
      corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were
      symptomatic and had 11 episodes of infection (2 patients had two different
      episodes with negative control between them). The most frequently identified
      virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was
      the presence or increased of apneas (75%) and the needed of oxygenotherapy.
      CONCLUSIONS: HRV infections are prevalent in the NICU, and preterm infants have a
      high risk of infections with clinical relevance.

PMID- 25066595
TI  - [Carnitine and acylcarnitine percentiles in very low birth weight premature
      newborn screening samples].

PMID- 25066596
TI  - [Plasma vitamin D levels in native and immigrant children under the age of 6
      years of different ethnic origins].
AB  - INTRODUCTION: Nutritional rickets is an emergent disease in Spain, and occurs
      particularly in black and dark-skinned infants and children from immigrant
      populations. The aim of this work was to ascertain the vitamin D reserve in a
      population of native and immigrant children under the age of 6 years. POPULATION
      AND METHODS: A prospective study was conducted at a Primary Healthcare Centre in
      Salt (Girona). PATIENTS: 307 children with the following origin and race
      distribution: Caucasian (n=85; 28%), Sub-Saharan (n=101; 32.5%); Maghrebi (n=87,
      28.0%); Central-American (n=20; 6.4%) and Indo-Pakistani (n=14; 4.5%). The
      biochemistry blood parameters studied were: calcium, phosphorus, alkaline
      phosphatase, 25-hydroxivitamin D, and parathormone. A nutritional survey was used
      to estimate calcium and vitamin D intake and degree of sun exposure. RESULTS:
      Vitamin D deficiency (<20 ng/ml) was detected in Caucasians (8%), Sub-Saharans
      (18%), Central-Americans (20%), Maghrebis (34.5%), and Indo-Pakistanis (64%). Of
      the children studied (n=9), 2.9% had serious vitamin D deficiency (< 10 ng/ml);
      only one child of Sub-Saharan origin met the biochemical criteria for classical
      rickets. The prevalence of vitamin D deficiency was significantly higher in
      children not receiving vitamin D supplements in the first year of life.
      CONCLUSIONS: Plasma vitamin D concentrations were deficient in 22.5% of children
      under the age of six, being more prevalent in children of Indo-Pakistani and
      Maghrebi origin.

PMID- 25066597
TI  - [Tuberous sclerosis: clinical characteristics and their relationship to
      genotype/phenotype].
AB  - INTRODUCTION: Tuberous sclerosis (TS) is an inherited disorder with multisystemic
      involvement and a high phenotypic variability. There are two genes that cause
      this condition: TSC1 and TSC2. OBJECTIVES: Our goal was to clinically
      characterize patients with TS followed up in the Pediatric Neurology Clinic of a
      tertiary hospital during the last 10 years, and correlate the genotype with the
      severity of neurological manifestations and imaging studies. PATIENTS AND
      METHODS: Retrospective analysis of patients with TS, including review of medical
      records and available MRI imaging. RESULTS: We studied 35 cases with a median age
      at diagnosis of ten months. Seizures were the first manifestation in 91.4% of
      cases, with a predominance of epileptic spasms. Over 50% had cognitive impairment
      and 49% behavioral disorders. A genetic study was performed on 24 children, and
      TSC2 mutations identified in 58.3% of them. Of the 11 cases of refractory
      epilepsy, six had the TSC2 gene mutation. In the group of eight patients with
      moderate/severe cognitive deficits, five had TSC2 mutations. We reviewed 26 MRI
      scans, in which it was observed that 76.9% had diffuse involvement of cerebral
      lobes, which reflects a greater burden of injury. Of the patients who had an MRI
      scan performed and had TSC2 mutations, all had a high tuber load, and5 of them
      had refractory epilepsy. DISCUSSION: In our sample we observe a high percentage
      of mutations in the TSC2 gene. This mutation carries a worse neurological
      prognosis, with drug-resistant epilepsy and a more severe cognitive impairment.

PMID- 25066598
TI  - Prb1, a subtilisin-like protease, is required for virulence and phenotypical
      traits in the chestnut blight fungus.
AB  - Subtilisin-like proteases are widely distributed and reported to be required for
      virulence in pathogenic fungi. In chestnut blight fungus Cryphonectria
      parasitica, prb1, encoding a putative subtilisin-like protease, was expressed and
      recombinant Prb1 protein was shown to have a protease activity in vitro. prb1
      deleted mutants exhibited reduced total protease activity by 60%. The Deltaprb1
      mutants showed a phenotype of reduced aerial hyphae, lower level of sporulation,
      and a significant reduction in virulence. Additionally, site-directed mutagenesis
      of Prb1 protein revealed that D195, H227, and S393 are critical for C. parasitica
      Prb1 function in vivo. Transcriptional analysis showed that deletion of prb1 also
      reduced the transcript accumulation levels for genes encoding key components of
      the heterotrimeric G-protein signaling pathway, including cpga1, cpgb1, cpgc1,
      and ste12. Furthermore, deletion of prb1 results in the accumulation of
      autophagic bodies in the fungus. Taken together, our results showed that prb1
      encoded protease functions in the regulation of virulence, phenotypical traits,
      and autophagy in C. parasitica. 

PMID- 25066599
TI  - Expanding the spectral tunability of plasmonic resonances in doped metal-oxide
      nanocrystals through cooperative cation-anion codoping.
AB  - We present a generalized cation-anion codoping methodology for the synthesis of
      monodisperse, doped metal-oxide nanocrystals (NCs) that exhibit near-infrared
      localized surface plasmon resonance (LSPR) with the highest reported quality
      factors. We demonstrate that, in addition to the use of common cation dopants,
      the incorporation of fluorine into the lattice as an anion dopant can further
      increase the free-carrier concentration within individual NCs; this supports the
      cooperative effects of mixed cation-anion doping in shifting the LSPR to higher
      energies. As a result, this method allows the LSPR of doped metal-oxide NCs to
      become tunable across a significantly broader wavelength range (1.5-3.3 MUm),
      circumventing the prior limitations on the highest possible LSPR energies
      associated with single-element doping for a given oxide host. The strategy of
      cation-anion codoping can offer new possibilities for the chemical design of
      doped semiconductor and metal-oxide NCs with tailored LSPR characteristics. 

PMID- 25066600
TI  - Access to artemisinin-based combination therapy (ACT) and quinine in malaria
      holoendemic regions of western Kenya.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) has been adopted as the
      most effective treatment against malaria in many endemic countries like Kenya
      while quinine has remained the second line. The objective of the current study
      was to assess access to Kenya's policy recommended anti-malarials, ACT and
      quinine in the public, private and not-for-profit drug outlets in western Kenya.
      METHODS: A cross-sectional survey using purposive sampling of 288 outlets (126
      public, 96 private, 66 not-for-profit) was conducted in western Kenya in two
      regions with varying Plasmodium falciparum endemicities. Information on access
      (availability, price, affordability) on ACT and quinine was collected using the
      WHO and Healthcare Associated Infection (HAI) standardized methodologies for
      availability, prices and affordability of drugs. From a Ministry of Health
      database, the following were included in the analyses: one (1) main public
      hospital, followed by random selection of five hospitals under this main
      facility. Eight other public outlets under each of the hospitals were selected,
      to a total of 96. Matching number of private outlets (n = 96), all (66) not-for
      profit outlets and additional 30 public health facilities were sampled to get the
      required sample size of 288. RESULTS: More public 111 (88.1%) and not-for-profit
      27 (40.9%) outlets stocked subsidized ACT (artemether-lumefantrine, AL). Other
      artemisinin-based combinations were widely available for both children 93 (96.9%)
      and adults 82 (85.0%) in private outlets. Frequent stock-outs were in public in
      106 (84%), reporting three times or more stock-outs in three months. Subsidized
      ACT (AL) was sold at median price of USD 0.94 and 0.75 in private and not-for
      profit outlets respectively. The costs was higher than recommended price of USD
      0.5 and requiring up to 0.20-0.25 days of disposable income for households in
      lowest economic status. CONCLUSION: There is low availability of subsidized ACT
      (AL) and higher frequency of stock-outs in government facilities, while private
      sector sells AL at higher prices, thus making it less affordable to many
      households. These factors determine the adherence to the dosing schedules during
      the treatment course and thus the evaluation of the subsidy policy, its
      implementation and role in malaria burden in this region is compulsory.

PMID- 25066601
TI  - Partial volume correction of brain perfusion estimates using the inherent signal
      data of time-resolved arterial spin labeling.
AB  - Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by
      partial volume effects (PVEs), arising due to voxel signal cross-contamination
      between different compartments. To address this issue, several partial volume
      correction (PVC) methods have been presented. Most previous methods rely on
      segmentation of a high-resolution T1 -weighted morphological image volume that is
      coregistered to the low-resolution ASL data, making the result sensitive to
      errors in the segmentation and coregistration. In this work, we present a
      methodology for partial volume estimation and correction, using only low
      resolution ASL data acquired with the QUASAR sequence. The methodology consists
      of a T1 -based segmentation method, with no spatial priors, and a modified PVC
      method based on linear regression. The presented approach thus avoids prior
      assumptions about the spatial distribution of brain compartments, while also
      avoiding coregistration between different image volumes. Simulations based on a
      digital phantom as well as in vivo measurements in 10 volunteers were used to
      assess the performance of the proposed segmentation approach. The simulation
      results indicated that QUASAR data can be used for robust partial volume
      estimation, and this was confirmed by the in vivo experiments. The proposed PVC
      method yielded probable perfusion maps, comparable to a reference method based on
      segmentation of a high-resolution morphological scan. Corrected gray matter (GM)
      perfusion was 47% higher than uncorrected values, suggesting a significant amount
      of PVEs in the data. Whereas the reference method failed to completely eliminate
      the dependence of perfusion estimates on the volume fraction, the novel approach
      produced GM perfusion values independent of GM volume fraction. The intra-subject
      coefficient of variation of corrected perfusion values was lowest for the
      proposed PVC method. As shown in this work, low-resolution partial volume
      estimation in connection with ASL perfusion estimation is feasible, and provides
      a promising tool for decoupling perfusion and tissue volume.

PMID- 25066602
TI  - Effects of rosuvastatin on serum lipids and arteriosclerosis in dyslipidemic
      patients with cerebral infarction.
AB  - BACKGROUND: We investigated the effect of rosuvastatin, 3-hydroxy-3
      methylglutaryl-coenzyme A reductase inhibitor, on serum lipids and
      arteriosclerosis in dyslipidemic patients with cerebral infarction. METHODS: The
      subjects were 24 patients with noncardiogenic cerebral infarction complicated by
      dyslipidemia (low-density lipoprotein cholesterol [LDL-C] >= 140 mg/dL). Serum
      lipids and highly sensitive C-reactive protein (hs-CRP) were measured at the
      start of the study and at 3 and 12 months after the initiation of oral
      rosuvastatin (5 mg/day). Cardio-ankle vascular index (CAVI), intima-media
      thickness (IMT), and plaque score (PS) were also determined at the start of the
      study and at 12 months. RESULTS: Of the 24 patients admitted, 17 were eligible
      for statistical analysis. Total cholesterol (TC), LDL-C, and non-high-density
      lipoprotein cholesterol (non-HDL-C) (mean [standard deviation {SD}], mg/dL) were
      significantly decreased at 3 months (TC, 149.4 [20.4]; LDL-C, 78.7 [18.6]; non
      HDL-C, 94.6 [21.7]) and at 12 months (TC, 154.9 [27.2]; LDL-C, 82.5 [23.3]; non
      HDL-C, 100.2 [28.8]) compared with the baseline data (TC, 232.8 [29.7]; LDL-C,
      162.2 [21.2]; non-HDL-C, 183.0 [27.7]). The serum hs-CRP level (mean [SD], ng/mL)
      was 1053.1 [818.8] at baseline, 575.2 [481.8] at 3 months, and 488.1 [357.7] at
      12 months. The decrease in this parameter at 12 months was statistically
      significant. There was a decrease, although not statistically significant, in
      CAVI (mean [SD]) at 12 months (right [Rt.] 8.7 [.9]; left [Lt.] 8.6 [1.0]),
      compared with baseline (Rt. 9.1 [1.1]; Lt. 9.0 [1.1]). The max-IMT (mean [SD],
      mm) was (Rt. 2.11 [.97]; Lt. 2.01 [.75]) at baseline and (Rt. 2.18 [.82]; Lt.
      2.06 [.79]) at 12 months of study treatment. The PS (mean [SD], mm) was 8.93
      [4.33] at baseline and 9.61 [4.79] at 12 months; neither parameter showed a
      significant change. CONCLUSIONS: Rosuvastatin at 5 mg/day significantly reduced
      serum levels of TC, LDL-C, non-HDL-C, and hs-CRP in dyslipidemic patients with
      cerebral infarction. No significant change in CAVI, max-IMT, or PS was noted
      after the study treatment.

PMID- 25066603
TI  - Infectious pathogens potentially transmitted by semen of the black variety of the
      Manchega sheep breed: Health constraints for conservation purposes.
AB  - Conservation of genetic resources from endangered breeds may be conducted through
      germinal banks. Preservation of healthy samples is paramount to avoid preserving
      pathogens shed with germinal products. The black variety of Manchega sheep (BMS),
      and endangered breed endemic to south-central Spain, is the subject of a
      conservation program; a germinal bank has been recently established. However,
      several pathogens circulating in BMS flocks may be shed with semen and threaten
      BMS preservation. Therefore, we investigated the sanitary status of BMS flocks
      and semen samples from 4 of the 17 flocks in which this variety is bred
      worldwide. A serological screening for Maedi-Visna virus, bluetongue virus,
      Pestivirus spp., Brucella spp., Coxiella burnetii, Chlamydophila spp.,
      Mycobacterium tuberculosis complex, Mycobacterium avium paratuberculosis,
      Anaplasma spp., Mycoplasma agalactiae, Toxoplasma gondii and Neospora caninum was
      performed to assess for pathogens potentially shed by semen. Semen samples from
      11 of the 35 BMS rams and 4 samples from coexisting rams of the white variety
      (WMS) were analyzed by PCR to detect Maedi-Visna virus, C. burnetii, Anaplasma
      marginale, Anaplasma phagocytophilum and T. gondii. Maedi-Visna virus RNA was
      detected in 3 semen samples (2 BMS and 1 WMS) while C. burnetii DNA was detected
      in 3 samples from WMS rams. Pathogens that can be transmitted by semen were
      present in BMS flocks, and Maedi-Visna virus and C. burnetii showed the highest
      potential for transmission by artificial insemination. Our results point to the
      need of testing semen samples kept for conservation purposes of BMS before using
      them for artificial insemination.

PMID- 25066604
TI  - High outgroup entitativity can inhibit intergroup retribution.
AB  - Understanding the psychological processes that are involved in the perpetuation
      and escalation of intergroup conflict remains an important goal for intergroup
      relations research. In the present research, we examined perceived outgroup
      entitativity as a potential determinant of intergroup hostility. In intergroup
      conflict situations, high-entitative outgroups are perceived as particularly
      deserving of retribution; however, high-entitative outgroups are also perceived
      as efficacious and capable of retaliating successfully, suggesting that people
      may inhibit hostility against high-entitative (vs. low-entitative) outgroups that
      are in a position to retaliate. We tested this prediction in two studies. In
      Study 1, we manipulated intergroup provocation and outgroup entitativity, and
      found that higher negative mood predicted greater aggression against a low
      entitative provoker outgroup, but failed to predict aggression against a high
      entitative provoker outgroup that was plausibly in a position to retaliate. In
      Study 2, we held provocation constant while manipulating outgroup entitativity
      and the possibility of retaliation by the outgroup, and found that people acted
      in a retributive manner against a high-entitative provoker outgroup only when the
      outgroup was not in a position to retaliate. Implications for intergroup conflict
      are discussed. 

PMID- 25066605
TI  - Direct comparison of first-contact versus longitudinal register-based case
      finding in the same population: early evidence that the incidence of
      schizophrenia may be three times higher than commonly reported.
AB  - BACKGROUND: The incidence of schizophrenia is commonly estimated by screening for
      psychosis among subjects presenting to psychiatric services. This approach (using
      a first-contact sampling frame) cannot account for cases that did not meet
      criteria for schizophrenia at first contact. We compared the usual approach
      directly with a register-based approach (using a longitudinal sampling frame)
      that also includes subjects initially diagnosed with other non-schizophrenic
      disorders. METHOD: We compared data from the Longitudinal Psychiatric Register
      (LPR) of The Hague over 1980-2009 with data previously collected in a first
      contact study, and applied both methods to calculate the incidence of
      schizophrenia for subjects aged 20-54 years in the same catchment area and over
      the same period (October 2000 to September 2005). We reconstructed treatment
      pathways and diagnostic histories up to the end of 2009 and performed sensitivity
      analyses. RESULTS: The LPR identified 843 first onsets of schizophrenia,
      corresponding to a treated incidence rate (IR) of 69 per 100,000 person-years
      [95% confidence interval (CI) 64-74]. The first-contact study identified 254
      first onsets, corresponding to a treated IR of 21 per 100,000 person-years (95%
      CI 18-23). Two-thirds of the difference was accounted for by subjects treated for
      other disorders before the onset of psychosis, and by patients in older age
      groups. CONCLUSIONS: The incidence of schizophrenia was three times higher in a
      longitudinal register study than in a high-quality first-contact study conducted
      in the same population. Risk estimates based only on first-contact studies may
      have been affected by selection bias.

PMID- 25066607
TI  - Suppression of AKT expression by miR-153 produced anti-tumor activity in lung
      cancer.
AB  - Lung cancer is one of the leading causes of cancer death worldwide. microRNAs
      have been shown to be a novel class of regulators in lung cancer. Here, we
      explored the role of miR-153 in the pathogenesis of lung cancer and its
      therapeutic potential. miR-153 was significantly decreased in lung cancer tissues
      than the adjacent tissues. The protein and mRNA levels of protein kinase B (AKT),
      which were shown to promote tumor growth, were both increased in lung cancer
      tissues than adjacent tissues. Overexpression of miR-153 significantly inhibited
      AKT protein expression, which were abrogated by co-transfection of AMO-153, the
      specific inhibitor of miR-153. Luciferase assay showed that transfection of miR
      153 markedly suppressed the fluorescent intensity of chimeric vectors carrying
      the 3'UTR of AKT1, while produced no effect on the mutant construct, indicating
      that AKT is regulated by miR-153. Overexpression of miR-153 significantly
      inhibited the proliferation and migration, and promoted apoptosis of cultured
      lung cancer cells in vitro, and suppressed the growth of xenograft tumors in
      vivo. Interestingly, lung cancer cells with lower endogenous miR-153 expression
      are more sensitive to ectopic overexpressed miR-153. The IC50 of miR-153 on lung
      cancer cells is positive correlated with the endogenous miR-153 level, while
      negative correlated with AKT level. Knockdown of AKT expression suppressed lung
      cancer cell proliferation. In summary, miR-153 exerted anti-tumor activity in
      lung cancer by targeting on AKT. The sensitivity of lung cancer cells to miR-153
      is determined by its endogenous miR-153 level. 

PMID- 25066608
TI  - Influence of self-assembling peptide nanofibre scaffolds on retinal
      differentiation potential of stem/progenitor cells derived from ciliary pigment
      epithelial cells.
AB  - Aim of the study was to investigate the influence of the self-assembling peptide
      nanofibre scaffolds (SAPNs) on the growth, proliferation and retinal neuronal
      differentiation of the stem/progenitor cells (SCs) derived from the ciliary
      pigment epithelium (CPE) of human cadaveric eye. Here SAPNs (RADA16-I, PM), which
      is well described in previous studies, commercially available and xeno-free. The
      CPE cells isolated were cultured in DMEM/F12 supplemented with N2 and growth
      factors such as basic fibroblast growth factor and epidermal growth factor,
      encapsulated in the scaffolds. The entrapped SCs actively expanded and formed
      clone-like clusters in the scaffolds. Many cells in the cluster were
      proliferating, as revealed by 5-bromo-2-deoxyuridine uptake and could be
      maintained for up to 6 days and expressed neural progenitor markers such as beta
      III tubulin, Nestin, Pax6 and Musashi1. Upon differentiation of these cells in
      conditioned medium, the cells exhibited retinal neuronal markers such as s-Opsin,
      rhodopsin and Recoverin. The RT2 profiler polymerase chain reaction array
      experiments showed selective gene expression, possibly involved in neural
      stem/progenitor cell adhesion and differentiation. These findings suggest the
      suitability of the three-dimensional culture system for the proliferation and
      maintenance of CPE stem/progenitor cells (CPE-NS) and for possible use in ex vivo
      studies of small molecules, drug deliveries for retinal diseases and for use in
      combination with directed stem/progenitor cell differentiation. and ultimately
      for tissue replacement therapies. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25066609
TI  - Isolating, screening and applying chromium reducing bacteria to promote growth
      and yield of okra (Hibiscus esculentus L.) in chromium contaminated soils.
AB  - Hexavalent chromium [Cr (VI)], extensively used in different industries, is one
      of the most toxic heavy metals. The Cr (VI) reducing bacteria could be helpful in
      decreasing its toxic effects. The present study was conducted to evaluate the
      potential of Cr (VI) reducing bacteria to improve growth and yield of okra
      (Hibiscus esculentus L.) in Cr-contaminated soils. Most of the selected bacterial
      isolates significantly increased the growth and yield of okra. Maximum response
      was observed in the plants inoculated with the isolate K12 where plant height,
      root length, fruit weight and number of fruits per plant increased up to 77.5
      percent, 72.6 percent, 1.4 fold and 2.9 fold, respectively. Moreover, inoculation
      with bacteria caused significant decrease in Cr (VI) concentration in soil and
      plant parts across all treatments. The maximum decrease of 69.6, 56.1 and 40.0
      percent in Cr (VI) concentrations in soil, plant vegetative parts and plant
      reproductive parts, respectively, was observed in the treatment inoculated with
      the strain K12. Based on amplification, sequencing and analysis of 16S rDNA
      sequence, the strain K12 was found belonging to genus Brucella and was designated
      as Brucella sp. K12. These findings suggest that the strain K12 may serve as a
      potential bioresource to improve crop production in Cr-contaminated soils.

PMID- 25066606
TI  - How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle.
AB  - During the late stage of the viral life cycle, HIV-1 Gag assembles into a
      spherical immature capsid, and undergoes budding, release, and maturation. Here
      we review events involved in immature capsid assembly from the perspective of
      five different approaches used to study this process: mutational analysis,
      structural studies, assembly of purified recombinant Gag, assembly of newly
      translated Gag in a cell-free system, and studies in cells using biochemical and
      imaging techniques. We summarize key findings obtained using each approach, point
      out where there is consensus, and highlight unanswered questions. Particular
      emphasis is placed on reconciling data suggesting that Gag assembles by two
      different paths, depending on the assembly environment. Specifically, in assembly
      systems that lack cellular proteins, high concentrations of Gag can spontaneously
      assemble using purified nucleic acid as a scaffold. However, in the more complex
      intracellular environment, barriers that limit self-assembly are present in the
      form of cellular proteins, organelles, host defenses, and the absence of free
      nucleic acid. To overcome these barriers and promote efficient immature capsid
      formation in an unfavorable environment, Gag appears to utilize an energy
      dependent, host-catalyzed, pathway of assembly intermediates in cells. Overall,
      we show how data obtained using a variety of techniques has led to our current
      understanding of HIV assembly. 

PMID- 25066610
TI  - Degradation of Jatropha curcas phorbol esters derived from Jatropha oil cake and
      their tumor-promoting activity.
AB  - Large amount of oil cake is generated during biodiesel production from Jatropha
      seeds. Although Jatropha oil cake is rich in plant nutrients, presence of toxic
      phorbol esters restricts the usage of oil cake as a fertilizer. The objective of
      this study is to evaluate the components and tumor promoting activity of phorbol
      esters in Jatropha oil cake-supplemented soil and plants grown in the treated
      soil. Contents and their biological activity of Jatropha phorbol esters in soil
      and plants were sequentially analyzed by high-performance liquid chromatography
      (HPLC) and in vitro cell transformation assay, respectively. Disappearance of
      Jatropha phorbol-ester-specific peaks were followed with HPLC during incubation
      of Jatropha oil cake with soil for five weeks. Along with the degradation of
      Jatropha phorbol ester in soil, tumor-promoting activity in the sample was also
      attenuated and ultimately disappeared. Jatropha phorbol esters and tumor
      promoting activity were not detected from mustard spinach grown in the Jatropha
      oil cake-supplemented soil. In addition, the esterase KM109 degrades DHPB (see
      definition below; Jatropha phorbol ester) and reduced its tumor-promoting
      activity. From these data, we conclude: (1) components and tumor promoting
      activity of Jatropha phorbol esters in the oil cake disappeared completely by
      incubation with soil for five-week, (2) Jatropha phorbol esters did not transfer
      into plants grown in the Jatropha oil cake-supplemented soil, and (3) DHPB can be
      degraded by esterase from soil bacterium. These observations are useful for
      utilization of Jatropha oil cake as a fertilizer. 

PMID- 25066611
TI  - Modulating the activation of hepatic stellate cells: a cunning way for metastatic
      cells to create a permissive soil for seeding in the liver?

PMID- 25066612
TI  - Patients with tattoo reactions have reduced quality of life and suffer from itch:
      Dermatology Life Quality Index and Itch Severity Score measurements.
AB  - BACKGROUND: Tattoos are a trend with increasing side-effects. The burden of local
      reaction with swelling, itching and discomfort may impel sufferers to consult
      medical assistance. OBJECTIVES: To assess tattoo reactions and their influence on
      quality of life and itching by utilizing the Dermatology Life Quality Index
      (DLQI) scoring system and Itch Severity Scale (ISS). METHODS: Patients attending
      the 'Tattoo Clinic' at Bispebjerg University Hospital, Denmark with tattoo
      problems spanning more than 3 months were invited. Forty patients participated
      during September-November 2012. Patients attending their routine consultations
      completed the ISS and DLQI questionnaires. RESULTS: Patients with tattoo
      reactions experienced reduced quality of life, DLQI score 7.4 and were burdened
      by itch, ISS score 7.2. Both DLQI and ISS results attained the level of
      discomfort of known skin diseases such as psoriasis, pruritus and eczema albeit
      the typical tattooed affected areas are smaller. CONCLUSION/DISCUSSION: Sufferers
      of tattoo reactions have reduced quality of life and are often burdened by
      itching attaining the level of other cumbersome afflictions recognized as
      dermatological diseases associated with itch. Tattoo reactions warrant diagnosis
      and treatment with same professional intent shared with other skin diseases.

PMID- 25066613
TI  - Functional properties of submucosal venules in the rat stomach.
AB  - Venules in the stomach may have intrinsic properties for maintaining active
      microcirculation drainage even during gastric filling. Properties of spontaneous
      and nerve-mediated activity of submucosal venules in the rat stomach were
      investigated. Changes in vasodiameter and intracellular Ca(2+) in venular smooth
      muscle cells (SMCs) were monitored by video tracking and Fluo-8 Ca(2+) imaging,
      respectively. Venular SMCs developed synchronous spontaneous Ca(2+) transients
      and corresponding rhythmic constrictions of the venules. Nominally Ca(2+)-free
      solution or an L-type Ca(2+) channel blocker (1 MUM nifedipine) disrupted the
      Ca(2+) transient synchrony and abolished spontaneous constrictions. Spontaneous
      constrictions were also prevented by inhibitors of sarcoplasmic reticulum Ca(2+)
      ATPase (10 MUM cyclopiazonic acid (CPA)), IP3 receptors (100 MUM 2-APB) or Ca(2+)
      activated Cl(-) channels (100 MUM niflumic acid). Transmural nerve stimulation
      (TNS) induced a long-lasting venular constriction that was abolished by alpha
      adrenoceptor antagonist (1 MUM phentolamine), while TNS evoked a sympathetic
      transient constriction of arterioles that was abolished by a combination of
      phentolamine and a P2 purinoceptor antagonist (10 MUM pyridoxal-phosphate-6
      azophenyl-2',4'-disulfonic acid (PPADS)). Consistently, P2X1 purinoceptor
      immunoreactivity was detected in arteriolar but not venular SMCs. Primary
      afferent nerve stimulation (300 nM capsaicin) caused a venular dilatation by
      releasing calcitonin gene-related peptide. Thus, Ca(2+) release from the
      sarcoplasmic reticulum may play a fundamental role in the generation of
      spontaneous Ca(2+) transients, while electrical coupling amongst venular SMCs via
      L-type Ca(2+) channel activation appears to be critical for Ca(2+) transient
      synchrony as well as spontaneous contractions. Sympathetic venular constrictions
      appear to be exclusively mediated by noradrenaline due to the lack of P2X1
      receptor in venular SMCs.

PMID- 25066615
TI  - ADHD in DSM-5: a field trial in a large, representative sample of 18- to 19-year
      old adults.
AB  - BACKGROUND: The DSM criteria for adult attention-deficit/hyperactivity disorder
      (ADHD) have not been tested in American Psychiatric Association (APA) field
      trials for either DSM-IV or DSM-5. This study aimed to assess: (a) the prevalence
      of ADHD according to DSM-5 criteria; (b) the factor solution that provides the
      best fit for ADHD symptoms; (c) the symptoms with the highest predictive value
      for clinical impairment; and (d) the best symptomatic threshold for each ADHD
      dimension (inattention and hyperactivity/impulsivity). METHOD: Trained
      psychologists evaluated 4000 young adults from the 1993 Pelotas Birth Cohort
      Study with an instrument covering all DSM-5 ADHD criteria. A series of
      confirmatory factor analyses (CFAs) tested the best factor structure. Complex
      logistic regressions assessed differential contributions of each symptom to
      clinical impairment. Receiver-operating characteristic (ROC) analyses tested
      which would be the best symptomatic cut-off in the number of symptoms for
      predicting impairment. RESULTS: The prevalence of DSM-5 ADHD was 3.55% [95%
      confidence interval (CI) 2.98-4.12]. The estimated prevalence of DSM-IV ADHD was
      2.8%. CFA revealed that a bifactor model with a single general factor and two
      specific factors provided the best fit for DSM-5 symptoms. Inattentive symptoms
      continued to be the most important predictors of impairment in adults. The best
      cut-offs were five symptoms of inattention and four symptoms of
      hyperactivity/impulsivity. CONCLUSIONS: Our results, combined with previous
      findings, suggest a 27% increase in the expected prevalence of ADHD among young
      adults, comparing DSM-IV to DSM-5 criteria. The DSM-5 symptomatic organization
      derived a similar factor structure for adults as DSM-IV symptoms. Data using DSM
      5 criteria support lowering the symptomatic threshold for diagnosing ADHD in
      adults.

PMID- 25066616
TI  - Obtaining the Patient's Voice from within Three Patient-Centered Medical Homes.
AB  - The purpose of this qualitative program was to determine if a trend exists across
      three LSU medical homes according to patient feedback concerning their
      experiences within the medical home for ongoing disease management and quality
      healthcare; and to obtain recommendations for the most effective way to involve
      patients in shaping system policies, procedures, and practices consistent with
      patient and family-centered care principles. A total of 94 adult patients
      participated in either cognitive interviews (n = 45) or structured focus groups
      (n = 49) using the Nominal Group Technique (NGT). Exit surveys collected
      demographic information and feedback from patients about opportunities for their
      involvement in shaping medical homes. Cognitive interviews and NGT sessions both
      revealed some patient-perceived gratifications (i.e., friendliness and
      helpfulness of the clinic staff), and deficiencies (i.e., improving scheduling of
      appointments and reducing wait time in the clinic) within these medical homes.
      However, the perceived gratifications far exceeded the deficiencies found within
      each of three LSU medical homes. 

PMID- 25066614
TI  - Central role of soluble adenylyl cyclase and cAMP in sperm physiology.
AB  - Cyclic adenosine 3',5'-monophosphate (cAMP), the first second messenger to be
      described, plays a central role in cell signaling in a wide variety of cell
      types. Over the last decades, a wide body of literature addressed the different
      roles of cAMP in cell physiology, mainly in response to neurotransmitters and
      hormones. cAMP is synthesized by a wide variety of adenylyl cyclases that can
      generally be grouped in two types: transmembrane adenylyl cyclase and soluble
      adenylyl cyclases. In particular, several aspects of sperm physiology are
      regulated by cAMP produced by a single atypical adenylyl cyclase (Adcy10, aka
      sAC, SACY). The signature that identifies sAC among other ACs, is their direct
      stimulation by bicarbonate. The essential nature of cAMP in sperm function has
      been demonstrated using gain of function as well as loss of function approaches.
      This review unifies state of the art knowledge of the role of cAMP and those
      enzymes involved in cAMP signaling pathways required for the acquisition of
      fertilizing capacity of mammalian sperm. This article is part of a Special Issue
      entitled: The role of soluble adenylyl cyclase in health and disease. 

PMID- 25066618
TI  - Home-based therapy for severe acute malnutrition with ready-to-use food.
AB  - Severe acute malnutrition is a devastating condition afflicting under-5 children
      in many developing countries, but concentrated in sub-Saharan Africa. This paper
      examines the development of home-based lipid-nutrient therapeutic foods for the
      treatment of acute malnutrition in sub-Saharan Africa and the adoption of these
      therapies as a standard of care for non-complicated cases of acute malnutrition.
      Several of the early key clinical and operational effectiveness trials are
      discussed as well as the adoption of home-based treatment as a standard operating
      procedure in regions where malnutrition is present. 

PMID- 25066617
TI  - Evaluating subjective domains of antipsychotic-induced adverse effects using
      heart rate variability.
AB  - AIMS: Antipsychotic-induced autonomic dysregulation may lead to a wide range of
      subjective side-effects in schizophrenia patients. Using heart rate variability
      (HRV) measures, we prospectively examined the relationship between subjective
      side-effects and cardiac autonomic regulation in unmedicated schizophrenia
      patients. METHODS: Forty-five unmedicated schizophrenia patients were assessed
      for antipsychotic-associated side-effects and HRV parameters at baseline and
      after 6 weeks of treatment. Psychiatric symptoms and subjective side-effects were
      assessed using the Positive and Negative Syndrome Scale (PANSS) and the Liverpool
      University Neuroleptic Side-effect Rating Scale (LUNSERS). RESULTS: Correlations
      between subjective adverse effects and HRV measures at baseline and at week 6
      varied. Nonetheless, the changes in the psychic side-effects domain were
      significantly correlated with the changes in time-domain HRV measures and sample
      entropy (SampEn). In addition, the change in SampEn was significantly associated
      with that in the scores of extrapyramidal, anticholinergic, miscellaneous, and
      red herring domains as well as the mean total LUNSERS score. CONCLUSION: Baseline
      HRV measures may predict clinical response and adverse events associated with
      treatment adherence. Also, subjective side-effects may correspond well with the
      changes in neurocardiac dynamics, and the changes in SampEn may effectively
      reflect subjective discomfort in patients receiving antipsychotic treatment.

PMID- 25066619
TI  - State of the Nigerian child - neglect of child and adolescent mental health: a
      review.
AB  - BACKGROUND: As most child health initiatives in Nigeria lack a child and
      adolescent mental health (CAMH) strategy, CAMH issues have remained obscure to
      the country's policy-makers. The lack of current and representative
      epidemiological data on the mental health of Nigerian children continues to be a
      barrier to advocacy for CAMH policy initiatives. In view of the importance of
      CAMH to national development, there must be a continued search for ways of
      bringing the state of CAMH in Nigeria to the attention of policy-makers.
      OBJECTIVES: To use information from UNICEF's State of the World's Children as
      proxy data to speculate on the state of child mental health in Nigeria. METHODS:
      With a view to discussing its CAMH implications, social and health indicators in
      the Nigerian child were extracted from UNICEF's 2012 edition. RESULTS: Most of
      the social and health indicators assessed reflect significant mental health
      risks. Up to 65% of households live on less than US$1.25 per day, child
      malnutrition is evident in up to 40% of children, and the primary and secondary
      school net enrolment ratios are only 63% and 25%, respectively. In addition, the
      rate of attendance for antenatal care was 45%, and only 39% of deliveries were
      supervised by skilled birth attendants. Child labour and under-age marriage is
      very common. A literature review demonstrates that children living in these
      circumstances are at significant risk of mental health problems. CONCLUSION:
      Current data on the state of Nigerian children contain indices that can serve as
      proxy information for the state of CAMH in the country. Policy-makers need to
      invest more in pre-emptive child health initiatives as a way of preserving the
      physical and mental health of children.

PMID- 25066620
TI  - Appropriate prescribing for acute childhood infections.

PMID- 25066621
TI  - The association between ICD interventions and mortality is independent of their
      modality: clinical implications.
AB  - BACKGROUND: Patients with severe structural heart disease have increased
      mortality after implantable cardioverter-defibrillator (ICD) shocks. Whether this
      is limited to ICD shock therapy only or extends also to no-shock therapies, such
      as antitachycardia pacing (ATP), is unclear. We investigated the impact of
      different ICD therapies on long-term mortality. METHODS: We enrolled 573 patients
      who underwent ICD implantation at our institution from 2004 to 2011. The
      population was divided into 3 groups: no device interventions (group 1), ATP
      interventions (group 2), and shock interventions (group 3). The endpoint was the
      all-cause mortality. RESULTS: Over a follow-up period of 48 months (range 1-110),
      447 (78%) had no device interventions, 71 (12%) had ATP therapy only, and 55
      (10%) had at least one shock intervention. All-cause mortality occurred in 94
      patients in group 1 (21%), 23 patients (43%) in group 2, and 21 patients (38%) in
      group 3. At multivariable Cox regression analysis, ATP intervention (HR: 1.8; 95%
      CI 1.1-3; P < 0.001), shock intervention (HR: 1.39; 95% CI 1.09-1.77; P = 0.008),
      age (HR: 1.05; 95% CI 1.02-1.07; P < 0.001), and LVEF (HR: 0.95; 95% CI 0.93
      0.98; P = 0.001) were predictors of all-cause mortality. No significant
      difference in mortality was found between group 2 and 3. CONCLUSION: Patients
      with ICDs who receive appropriate interventions are at increased risk of
      mortality. Such risk is not dependent on different types of ICD therapy, such as
      shocks or ATP. Our data suggest that sustained ventricular arrhythmias per se
      have a negative impact on prognosis rather than modality of ICD therapy.

PMID- 25066622
TI  - Factors affecting the computation of the 13C shielding in disaccharides.
AB  - Knowledge of the three-dimensional structures of glycans and glycoproteins is
      useful for a full understanding of molecular processes in which glycans are
      involved, such as antigen-recognition and virus infection, to name a few. Among
      the ubiquitous nuclei in glycan molecules, the (13)C nucleus is an attractive
      candidate for computation of theoretical chemical shifts at the quantum chemical
      level of theory to validate and determine glycan structures. For this purpose, it
      is important to determine, first, which carbons can be used as probes to sense
      conformational changes and, second, all factors that affect the computation of
      the shielding, at the density functional theory (DFT) level of theory, of those
      carbons. To answer such questions, we performed a series of analyses on low
      energy conformations, obtained by sampling the glycosidic torsional angles (phi,
      psi) every 10 degrees , of 12 disaccharides. Our results provide evidence that:
      (i) the carbons that participate in the glycosidic linkage are the most sensitive
      probes with which to sense conformational changes of disaccharides; (ii) the
      rotation of the hydroxyl groups closest to the glycosidic linkage significantly
      affects the computation of the shieldings of the carbons that participate in the
      glycosidic linkage; (iii) it is not possible to obtain the shieldings of one
      disaccharide from the computed values of a different disaccharide or from those
      disaccharides that differ in the anomeric state; and (iv) a proper basis set
      distribution, a functional, and a step size, with which to sample the
      conformational space, are necessary to compute shieldings accurately and rapidly.

PMID- 25066623
TI  - Subjectively perceived personality and mood changes associated with subthalamic
      stimulation in patients with Parkinson's disease.
AB  - BACKGROUND: Clinical and ethical implications of personality and mood changes in
      Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation
      (STN-DBS) are under debate. Although subjectively perceived personality changes
      are often mentioned by patients and caregivers, few empirical studies concerning
      these changes exist. Therefore, we analysed subjectively perceived personality
      and mood changes in STN-DBS PD patients. METHOD: In this prospective study of the
      ELSA-DBS group, 27 PD patients were assessed preoperatively and 1 year after STN
      DBS surgery. Two categories, personality and mood changes, were analysed with
      semi-structured interviews. Patients were grouped into personality change yes/no,
      as well as positive/negative mood change groups. Caregivers were additionally
      interviewed about patients' personality changes. Characteristics of each group
      were assessed with standard neurological and psychiatric measurements. Predictors
      for changes were analysed. RESULTS: Personality changes were perceived by six of
      27 (22%) patients and by 10 of 23 caregivers (44%). The preoperative hypomania
      trait was a significant predictor for personality change perceived by patients.
      Of 21 patients, 12 (57%) perceived mood as positively changed. Higher apathy and
      anxiety ratings were found in the negative change group. CONCLUSIONS: Our results
      show that a high proportion of PD patients and caregivers perceived personality
      changes under STN-DBS, emphasizing the relevance of this topic. Mood changed in
      positive and negative directions. Standard measurement scales failed to
      adequately reflect personality or mood changes subjectively perceived by
      patients. A more individualized preoperative screening and preparation for
      patients and caregivers, as well as postoperative support, could therefore be
      useful.

PMID- 25066626
TI  - Spinal growth modulation with posterior unilateral elastic tether in immature
      swine model.
AB  - BACKGROUND CONTEXT: Fusionless scoliosis surgery is frequently performed in
      children. Many studies have analyzed the effects of spinal growth modulation by
      tethering the anterior and anterolateral aspects of the spine in animal models.
      However, few studies have reported the disc health and spinal motion in spines
      with posterior unilateral elastic tethering. PURPOSE: To analyze the regional
      radiography, biochemistry, and histology of spinal motion segments fixed by
      posterior unilateral elastic tethering. STUDY DESIGN: A randomized controlled
      trial. OUTCOME MEASURES: Preoperative and postoperative radiographs of the spines
      were taken. After an 8-week recovery period, the spines were harvested en bloc
      and underwent radiographic, biochemical, and histologic analyses. METHODS:
      Fifteen 3-month-old swine were randomly divided into three groups.
      Instrumentation was performed posteriorly in the swine. In the elastic fixation
      (EF) group, five swine were instrumented on the left side of the lumbar vertebrae
      from L1 to L5 with pedicle screws that were connected with a unilateral elastic
      tether with tension to produce a curve on the spine. The same surgery was
      performed in the five animals of the metal rod fixation (MF) group, in which the
      screws were connected with metal rods and curves were established. In the control
      group, five animals were instrumented with five screws with no connecting cable.
      RESULTS: Scoliosis and lordosis were created in the coronal and sagittal planes
      in both the EF and MF groups. On average, the Cobb angles were 12.16 degrees +/
      1.37 degrees  and 9.10 degrees +/-2.02 degrees  (p=.023) in the coronal plane and
      17.44 degrees +/-11.29 degrees  and 5.32 degrees +/-3.06 degrees  (p=.049) in the
      sagittal plane in the two groups, respectively. The vertebrae and discs wedged on
      the tethered side in the two groups showed no significant differences (p>.05).
      The thickness of end-plate epiphysis on the fixed side was significantly
      decreased in the two groups (p=.032 and p=.024). No apparent change was found in
      the gross morphology of the discs in the two groups. The distribution of collagen
      types I and II decreased and that of matrix metalloprotease-3 (MMP-3) increased
      in both the EF and MF groups. Additionally, the proteoglycan synthesis decreased
      in the two groups. CONCLUSIONS: Unilateral elastic tethering resulted in
      vertebral wedging and scoliosis. Although changes in collagen and MMP-3
      distribution, proteoglycan synthesis, end-plate epiphysis, and disc thickness
      were observed, the tethered discs and end plates did not demonstrate gross
      morphologic signs of degeneration.

PMID- 25066627
TI  - Antibiotics for acute pyelonephritis in children.
AB  - BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial
      infections in infants. The most severe form of UTI is acute pyelonephritis, which
      results in significant acute morbidity and may cause permanent kidney damage.
      There remains uncertainty regarding the optimum antibiotic regimen, route of
      administration and duration of treatment. This is an update of a review that was
      first published in 2003 and updated in 2005 and 2007. OBJECTIVES: To evaluate the
      benefits and harms of antibiotics used to treat children with acute
      pyelonephritis. The aspects of therapy considered were 1) different antibiotics,
      2) different dosing regimens of the same antibiotic, 3) different duration of
      treatment, and 4) different routes of administration. SEARCH METHODS: We searched
      the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE,
      reference lists of articles and conference proceedings without language
      restriction to 10 April 2014. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled trials comparing different antibiotic agents, routes, frequencies or
      durations of therapy in children aged 0 to 18 years with proven UTI and acute
      pyelonephritis were selected. DATA COLLECTION AND ANALYSIS: Four authors
      independently assessed study quality and extracted data. Statistical analyses
      were performed using the random-effects model and the results expressed as risk
      ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data
      with 95% confidence intervals (CI). MAIN RESULTS: This updated review included 27
      studies (4452 children). This update included evidence from three new studies,
      and following re-evaluation, a previously excluded study was included because it
      now met our inclusion criteria.Risk of bias was assessed as low for sequence
      generation (12 studies), allocation concealment (six studies), blinding of
      outcome assessors (17 studies), incomplete outcome reporting (19 studies) and
      selective outcome reporting (13 studies). No study was blinded for participants
      or investigators. The 27 included studies evaluated 12 different comparisons. No
      significant differences were found in duration of fever (2 studies, 808 children:
      MD 2.05 hours, 95% CI -0.84 to 4.94), persistent UTI at 72 hours after commencing
      therapy (2 studies, 542 children: RR 1.10, 95% CI 0.07 to 17.41) or persistent
      kidney damage at six to 12 months (4 studies, 943 children: RR 0.82, 95% CI 0.59
      to 1.12) between oral antibiotic therapy (10 to 14 days) and intravenous (IV)
      therapy (3 days) followed by oral therapy (10 days). Similarly, no significant
      differences in persistent bacteriuria at the end of treatment (4 studies, 305
      children: RR 0.78, 95% CI 0.24 to 2.55) or persistent kidney damage (4 studies,
      726 children: RR 1.01, 95% CI 0.80 to 1.29) were found between IV therapy (three
      to four days) followed by oral therapy and IV therapy (seven to 14 days). No
      significant differences in efficacy were found between daily and thrice daily
      administration of aminoglycosides (1 study, 179 children, persistent clinical
      symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). Adverse events were mild
      and uncommon and rarely resulted in discontinuation of treatment. AUTHORS'
      CONCLUSIONS: This updated review increases the body of evidence that oral
      antibiotics alone are as effective as a short course (three to four days) of IV
      antibiotics followed by oral therapy for a total treatment duration of 10 to 14
      days for the treatment of acute pyelonephritis in children. When IV antibiotics
      are given, a short course (two to four days) of IV therapy followed by oral
      therapy is as effective as a longer course (seven to 10 days) of IV therapy. If
      IV therapy with aminoglycosides is chosen, single daily dosing is safe and
      effective. Insufficient data are available to extrapolate these findings to
      children aged less than one month of age or to children with dilating
      vesicoureteric reflux (grades III-V). Further studies are required to determine
      the optimal total duration of antibiotic therapy required for acute
      pyelonephritis.

PMID- 25066628
TI  - Toxicokinetics and absolute oral bioavailability of melamine in broiler chickens.
AB  - The objective of this study was to investigate the toxicokinetic characteristics
      of melamine in broilers due to the limited information available for livestock.
      Melamine was then administered to broiler chickens at an intravenous (i.v.) or
      oral (p.o.) dosage of 5.5 mg/kg of body weight, and plasma samples were collected
      up to 48 h. The concentration of melamine in each plasma sample was analyzed
      using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Melamine was
      measurable up to 24 h after i.v. and p.o. administration. A one-compartment model
      was developed to describe the toxicokinetics of melamine in broilers. Following
      i.v. administration, the values for the elimination half-life (t(1/2beta)), the
      volume of distribution (Vd ), and the clearance (CL) were 4.42 +/- 1.02 h, 00.52
      +/- 0.18 L/kg, and 0.08 +/- 0.01 L/h/kg, respectively. The absolute oral
      bioavailability (F) was 95.63 +/- 3.54%. The results suggest that most of the
      administered melamine is favorably absorbed from the alimentary tract and rapidly
      cleared by the kidneys in broiler chickens.

PMID- 25066630
TI  - Advanced complicated diabetes mellitus is associated with a reduced risk of
      thoracic and abdominal aortic aneurysm rupture: a population-based cohort study.
AB  - BACKGROUND: Studies have associated diabetes mellitus (DM) with the reduced risk
      of abdominal aortic aneurysm and thoracic aortic aneurysm and dissection. We used
      the national insurance data of Taiwan to examine these correlations for an Asian
      population. The association was also evaluated by DM severity. METHODS: We
      identified 160,391 patients with type 2 DM diagnosed from 1998 to 2008 and
      646,710 comparison subjects without DM, frequency matched by diagnosis date, sex
      and age (mainly the elderly). The DM severity was partitioned into advanced and
      uncomplicated status according to DM-related comorbidities. RESULTS: By the end
      of 2010, the overall pooled incidence rate of thoracic aortic aneurysm and
      abdominal aortic aneurysm was 15% lower in the type 2 DM cohort than in non-DM
      cohort, with an adjusted hazard ratio of 0.64 [95% confidence interval (CI) 0.56
      0.74] in the multivariable Cox model. Patients with advanced type 2 DM were
      significantly associated with reduced thoracic aortic aneurysm rupture and
      abdominal aortic aneurysm without rupture, with adjusted hazard ratios of 0.50
      (95% CI 0.35-0.71) and 0.53 (95% CI 0.40-0.69), respectively. Uncomplicated type
      2 DM was also associated with reduced abdominal aortic aneurysm without rapture
      (aHR = 0.58, 95% CI 0.45-0.74). CONCLUSIONS: Our results demonstrate that
      patients with diabetes in this Asian population have reduced prevalence of
      thoracic and abdominal aortic aneurysms. The observed paradoxical inverse
      relationship between severity of DM and aortic aneurysms is clear. Further
      research is required to investigate the underlying mechanisms for the reduced
      risk of aortic aneurysms associated with diabetes.

PMID- 25066629
TI  - Rituximab with chemotherapy in children and adolescents with central nervous
      system and/or bone marrow-positive Burkitt lymphoma/leukaemia: a Children's
      Oncology Group Report.
AB  - Children and adolescents with Burkitt Lymphoma (BL) and combined central nervous
      system (CNS) and bone marrow involvement still have a poor prognosis with
      chemotherapy alone. We therefore investigated in children and adolescents with
      bone marrow (>=25% blasts) and/or CNS-positive Burkitt lymphoma the
      chemoimmunotherapy combination of rituximab (375 mg/m(2) ) and the standard
      chemotherapy arm of our previously reported French-American-British (FAB)
      Lymphome Malins de Burkitt (LMB) 96 trial. Central pathological and cytogenetic
      characterization was also performed. There were 40 evaluable patients with
      Burkitt histology (25 with leukaemia and 15 with CNS disease +/- leukaemia). The
      chemoimmunotherapy regimen was well tolerated. The incidence of grade III/IV
      mucositis during induction cycles with combined chemotherapy and rituximab was
      31% and 26%, respectively. The 3-year event-free survival (EFS)/overall survival
      (OS) was 90% (95% confidence interval [CI], 76-96%) in the entire cohort and 93%
      (95% CI, 61-99%) in patients with CNS disease. Based on the results of this
      trial, an international randomized study of FAB/LMB 96 chemotherapy +/- rituximab
      for high-risk patients is currently under investigation.

PMID- 25066631
TI  - Robust expansion of dendritic cells in vivo by hydrodynamic FLT3L-FC gene
      transfer.
AB  - Due to low numbers of endogenous dendritic cells (DCs) in vivo, exogenous DC
      poietin Fms-like tyrosine kinase 3-ligand (FLT3L) is routinely used to generate
      DC for subsequent studies. We engineered a novel FLT3L-FC DNA construct that,
      when combined with hydrodynamic gene transfer (HDT), induced robust DC expansion
      in mice. DC generated in vivo by FLT3L-FC HDT produced cytokines in response to
      stimulation by an array of TLR agonists and promoted T cell proliferation. The
      FLT3L-FC protein produced in vivo spontaneously homodimerized to enable effective
      FLT signaling and the FC-domain enhanced its plasma half-life, providing an
      improved reagent and method to boost DC numbers. 

PMID- 25066632
TI  - Collagenase digestion down-regulates the density of CD27 on lymphocytes.
AB  - Collagenases are widely used for tissue digestion in experiments due to their
      potent hydrolysis of connective tissue. CD27, also known as tumor necrosis factor
      receptor superfamily 7 (TNFRSF7), is limited to be expressed on the cells of the
      lymphoid lineage. In our preliminary research, we found that CD27 on NK cells was
      almost disappeared with the digestion of type I collagenase for 90min. This
      phenomenon suggests that the process of tissue digestion may affect the density
      of CD27 on cells. In order to verify this, the lungs of mice were digested with
      types I and IV collagenase or grinded, respectively. The percentage of CD27(+)
      cells and the density of CD27 on cells were assayed by flow cytometry. The data
      presented that the percentage of CD27(+) cells and the density of CD27 on
      lymphocytes gradually decreased with the time of digestion with type I or IV
      collagenase. We also detected that the density of CD11b on NK cells was not
      affected by collagenase digestion. Collectively, the findings of the present
      study suggest that the collagenase digestion has a selective effect on the
      density of molecules on cells. 

PMID- 25066633
TI  - Development of antibodies for determination of alkylresorcinol metabolites in
      human urine and elucidation of ELISA cross-reactivity.
AB  - Alkylresorcinols (ARs) are amphiphilic phenolic lipids and their two main
      metabolites, 3-(3,5-dihydroxyphenyl)-propanoic acid (DHPPA) and 3,5
      dihydroxybenzoic acid (DHBA), can be used as biomarkers of whole grain wheat and
      rye intake. The aim of this study was to develop antibodies against DHBA and
      DHPPA for use in ELISA analysis. Good calibration curves were obtained for ELISA
      using alkaline phosphatase (AP) conjugates. The highest sensitivity for DHPPA was
      found using a reagent combination of anti-DHPPA-BSA and DHPAA-AP in a direct
      ELISA (IC50=1.5MUmol/L), and for DHBA using a reagent combination of anti-DHBA-OV
      and DHBA-AP (IC50=1.3MUmol/L). Calibration was conducted in the linear range (0.3
      27.4MUmol/L), with limit of detection (LOD) 0.1MUmol/L. Intra and inter CVs was
      in the range of 0.7-7.2% and 5.1-11.5%, respectively, for DHPPA and 1.3-9.4% and
      3.5-20%, respectively, for DHBA. Mean recovery was 104% for DHPPA and 102% for
      DHBA. The ELISA method developed was then used for analysis of 120 urine samples
      from free-living men and women that had previously been analysed by gas
      chromatography-mass spectrometry (GC-MS). ELISA produced several-fold higher
      values than GC-MS. Application of high-resolution Orbitrap mass spectrometry (HR
      Orbitrap MS) allowed several compounds, including novel putative AR metabolites,
      to be identified, synthesised and confirmed as compounds with high ELISA cross
      reactivity. 

PMID- 25066634
TI  - Phenolic metabolites and substantial microbiome changes in pig feces by ingesting
      grape seed proanthocyanidins.
AB  - Proanthocyanidin (PAC) consumption has been linked to better colonic health, but
      PACs are poorly absorbed, making them a target for colonic metabolism. The
      resulting metabolites are low molecular weight and could potentially be absorbed.
      To understand the effects of dietary PACs it would be important to resolve the
      metabolic issue and link these changes to microbial population changes in a
      suitable model for human digestion. Here, six crossbred female pigs were fed a
      diet containing 1% (w/w) of MegaNatural(r) Gold grape seed extract (GSE) daily
      for 6 days. Fecal samples were analyzed by normal phase LC coupled to
      fluorescence detection and LC-MS/ToF. DNA was extracted from pig fecal samples
      and the V3/V4 region of the 16S rRNA gene was sequenced using an Illumina MiSeq.
      Intact parent PACs (dimer-pentamer) were observed in the feces on days 3 and 6 at
      similar high levels (~400 mg kg(-1) total) during ingestion of GSE but were
      absent 48 h post-feeding. The major phenolic metabolites were 4
      hydroxyphenylvaleric acid and 3-hydroxybenzoic acid which increased by ~30 and 3
      mg kg(-1) respectively. The GSE diet also caused an ecological shift in the
      microbiome, dramatically increasing Lachnospiraceae, Clostridales, Lactobacillus
      and Ruminococcacceae. The relationship between dietary PACs and colon health may
      be attributable to the altered bacterial populations or phenolic compounds in the
      colon. 

PMID- 25066635
TI  - Screening for mood disorders after stroke: a systematic review of psychometric
      properties and clinical utility.
AB  - BACKGROUND: Routine mood screening is recommended after stroke. However,
      clinicians report difficulty selecting appropriate tools from the wide range
      available. We aimed to systematically review the psychometric properties and
      clinical utility of mood screening tools for stroke survivors. METHOD: Electronic
      databases (AMED, EMBASE, CINAHL, Medline and PsycINFO) were searched to identify
      studies assessing the sensitivity and specificity of mood screening tools. Tools
      that demonstrated at least 80% sensitivity and 60% specificity with stroke
      survivors with identifiable cut-off scores indicating major and/or any mood
      disorder in at least one study were selected and clinical utility was assessed.
      Those with high clinical utility (against predefined criteria) were selected for
      recommendation. RESULTS: Thirty papers examining 27 screening tools were
      identified and 16 tools met the psychometric and clinical utility criteria: 10
      were verbal self-report tools, four were observational and two incorporated
      visual prompts for those with communication problems. Only the Stroke Aphasic
      Depression Questionnaire -Hospital version (SADQ-H) met all the psychometric and
      utility criteria. The nine-item Patient Health Questionnaire (PHQ-9) can detect
      major depression and the 15-item Geriatric Depression Scale (GDS-15) can identify
      milder symptoms; both are feasible to use in clinical practice. The Hospital
      Anxiety and Depression Scale (HADS) was the only tool able to identify anxiety
      accurately, but clinical utility was mixed. CONCLUSIONS: Valid and clinically
      feasible mood screening tools for stroke have been identified but methodological
      inconsistency prevented recommendations about the optimal cut-off scores.

PMID- 25066636
TI  - Understanding jumping to conclusions in patients with persecutory delusions:
      working memory and intolerance of uncertainty.
AB  - BACKGROUND: Persecutory delusions are a key psychotic experience. A reasoning
      style known as 'jumping to conclusions' (JTC) - limited information gathering
      before reaching certainty in decision making - has been identified as a
      contributory factor in the occurrence of delusions. The cognitive processes that
      underpin JTC need to be determined in order to develop effective interventions
      for delusions. In the current study two alternative perspectives were tested:
      that JTC partially results from impairment in information-processing capabilities
      and that JTC is a motivated strategy to avoid uncertainty. METHOD: A group of 123
      patients with persistent persecutory delusions completed assessments of JTC (the
      60:40 beads task), IQ, working memory, intolerance of uncertainty, and
      psychiatric symptoms. Patients showing JTC were compared with patients not
      showing JTC. RESULTS: A total of 30 (24%) patients with delusions showed JTC.
      There were no differences between patients who did and did not jump to
      conclusions in overall psychopathology. Patients who jumped to conclusions had
      poorer working memory performance, lower IQ, lower intolerance of uncertainty and
      lower levels of worry. Working memory and worry independently predicted the
      presence of JTC. CONCLUSIONS: Hasty decision making in patients with delusions
      may partly arise from difficulties in keeping information in mind. Interventions
      for JTC are likely to benefit from addressing working memory performance, while
      in vivo techniques for patients with delusions will benefit from limiting the
      demands on working memory. The study provides little evidence for a contribution
      to JTC from top-down motivational beliefs about uncertainty.

PMID- 25066637
TI  - The rise of systems pharmacology in drug discovery and development.

PMID- 25066638
TI  - Successful treatment of systemic and central nervous system post-transplant
      lymphoproliferative disorder without the use of high-dose methotrexate or
      radiation.
AB  - Post-transplant lymphoproliferative disorder (PTLD) describes a spectrum of
      conditions with highest incidence in the first year post-solid organ transplant
      in pediatric patients. Central nervous system (CNS) involvement with PTLD carries
      high mortality risk with no consensus on optimal therapeutic regimen. We present
      the case of a 7-year old heart transplant patient diagnosed with widespread
      monomorphic, CD20+, Epstein-Barr virus-positive PTLD, including CNS involvement.
      In addition to immunosuppression reduction and rituximab, she was treated with
      multiagent systemic and intrathecal chemotherapy. She achieved a prompt and
      complete clinical and radiologic remission, which has been sustained for over 46
      months since diagnosis.

PMID- 25066639
TI  - The dominant role of chalcogen bonding in the crystal packing of 2D/3D aromatics.
AB  - The chalcogen bond is a nonclassical sigma-hole-based noncovalent interaction
      with emerging applications in medicinal chemistry and material science. It is
      found in organic compounds, including 2D aromatics, but has so far never been
      observed in 3D aromatic inorganic boron hydrides. Thiaboranes, harboring a sulfur
      heteroatom in the icosahedral cage, are candidates for the formation of chalcogen
      bonds. The phenyl-substituted thiaborane, synthesized and crystalized in this
      study, forms sulfur???pi type chalcogen bonds. Quantum chemical analysis revealed
      that these interactions are considerably stronger than both in their organic
      counterparts and in the known halogen bond. The reason is the existence of a
      highly positive sigma-hole on the positively charged sulfur atom. This discovery
      expands the possibilities of applying substituted boron clusters in crystal
      engineering and drug design. 

PMID- 25066641
TI  - Quantitative imaging of the magnetic configuration of modulated nanostructures by
      electron holography.
AB  - By means of off-axis electron holography the local distribution of the magnetic
      induction within and around a poly-crystalline Permalloy (Ni81Fe19) thin film is
      studied. In addition the stray field above the sample is measured by magnetic
      force microscopy on a larger area. The film is deposited on a periodically
      nanostructured (rippled) Si substrate, which was formed by Xe(+) ion beam
      erosion. This introduces the periodical ripple shape to the Permalloy film. The
      created ripple morphology is expected to modify the magnetization distribution
      within the Permalloy and to induce dipolar stray fields. These stray fields play
      an important role in spinwave dynamics of periodic nanostructures like magnonic
      crystals. Micromagnetic simulations estimate those stray fields in the order of
      only 10 mT. Consequently, their experimental determination at nanometer spatial
      resolution is highly demanding and requires advanced acquisition and
      reconstruction techniques such as electron holography. The reconstructed magnetic
      phase images show the magnetized thin film, in which the magnetization direction
      follows mainly the given morphology. Furthermore, a closer look to the
      Permalloy/carbon interface reveals stray fields at the detection limit of the
      method in the order of 10 mT, which is in qualitative agreement with the
      micromagnetic simulations.

PMID- 25066640
TI  - Use of a novel cell adhesion method and digital measurement to show stimulus
      dependent variation in somatic and oral ciliary beat frequency in Paramecium.
AB  - When Paramecium encounters positive stimuli, the membrane hyperpolarizes and
      ciliary beat frequency increases. We adapted an established immobilization
      protocol using a biological adhesive and a novel digital analysis system to
      quantify beat frequency in immobilized Paramecium. Cells showed low mortality and
      demonstrated beat frequencies consistent with previous studies. Chemoattractant
      molecules, reduction in external potassium, and posterior stimulation all
      increased somatic beat frequency. In all cases, the oral groove cilia maintained
      a higher beat frequency than mid-body cilia, but only oral cilia from cells
      stimulated with chemoattactants showed an increase from basal levels. 

PMID- 25066642
TI  - Preoperative TSH level and risk of thyroid cancer in patients with nodular
      thyroid disease: nodule size contribution.
AB  - BACKGROUND: Many reports have supported the relationship between high
      preoperative TSH levels and risk of thyroid cancer in nodular thyroid disease
      (NTD). OBJECTIVES: We investigated whether TSH levels are related to the risk of
      differentiated thyroid carcinoma (DTC) in patients who have undergone total
      thyroidectomy for NTD. The relationship between TSH and size of malignant nodule
      was investigated. Finally, we assessed whether TSH levels are related to DTC and
      presence of additional benign nodules. PATIENTS AND METHODS: A retrospective
      study of 980 patients was conducted. Variables included age at diagnosis, TSH
      level, nodule size, gender, final histology (benign versus DTC), and type of
      malignancy. RESULTS: Malignancy was present in 261 (26.6%) patients. These
      patients had higher median TSH levels as compared to those with no malignancy
      (1.61 mU/L (0.9-2.5) versus 0.9 mU/L (0.3-1.6); p-value<0.001). TSH was higher in
      patients with DTC in whom the largest nodule was malignant than in patients in
      whom the largest nodule was benign (1.80 mU/L (1.1-2.6) versus 1.38 mU/L (0.7
      2.1) respectively; p-value=0.025). A significant correlation was seen between
      malignant nodule size and TSH level, but not between TSH levels and size of the
      largest benign nodule. CONCLUSIONS: Our study supported an association between
      preoperative TSH levels and risk of DTC in patients with NTD. There was also a
      direct relationship between malignant nodule size and TSH levels. By contrast, no
      relationship was found between the size of benign nodules and TSH levels.

PMID- 25066644
TI  - Interlocked loops trigger lineage specification and stable fates in the
      Drosophila nervous system.
AB  - Multipotent precursors are plastic cells that generate different, stable fates at
      the correct number, place and time, to allow tissue and organ formation. While
      fate determinants are known to trigger specific transcriptional programs, the
      molecular pathway driving the progression from multipotent precursors towards
      stable and specific identities remains poorly understood. Here we demonstrate
      that, in Drosophila neural precursors, the glial determinant glial cell missing
      (Gcm) acts as a 'time bomb' and triggers its own degradation once the glial
      programme is stably activated. This requires a sequence of transcriptional and
      posttranscriptional loops, whereby a Gcm target first affects the expression and
      then acetylation of the fate determinant, thus controlling Gcm levels and
      stability over time. Defective homeostasis between the loops alters the
      neuron:glia ratio and freezes cells in an intermediate glial/neuronal phenotype.
      In sum, we identify an efficient strategy triggering cell identity, a process
      altered in pathological conditions such as cancer. 

PMID- 25066643
TI  - Augmented cystine-glutamate exchange by pituitary adenylate cyclase-activating
      polypeptide signaling via the VPAC1 receptor.
AB  - In the central nervous system, cystine import in exchange for glutamate through
      system xc- is critical for the production of the antioxidant glutathione by
      astrocytes, as well as the maintenance of extracellular glutamate. Therefore,
      regulation of system xc- activity affects multiple aspects of cellular physiology
      and may contribute to disease states. Pituitary adenylate cyclase-activating
      polypeptide (PACAP) is a neuronally derived peptide that has already been
      demonstrated to modulate multiple aspects of glutamate signaling suggesting PACAP
      may also target activity of cystine-glutamate exchange via system xc-. In this
      study, 24-h treatment of primary cortical cultures containing neurons and glia
      with PACAP concentration-dependently increased system xc- function as measured by
      radiolabeled cystine uptake. Furthermore, the increase in cystine uptake was
      completely abolished by the system xc- inhibitor, (S)-4-carboxyphenylglycine
      (CPG), attributing increases in cystine uptake specifically to system xc-
      activity. Time course and quantitative PCR results indicate that PACAP signaling
      may increase cystine-glutamate exchange by increasing expression of xCT, the
      catalytic subunit of system xc-. Furthermore, the potentiation of system xc-
      activity by PACAP occurs via a PKA-dependent pathway that is not mediated by the
      PAC1R, but rather the shared vasoactive intestinal polypeptide receptor VPAC1R.
      Finally, assessment of neuronal, astrocytic, and microglial-enriched cultures
      demonstrated that only astrocyte-enriched cultures exhibit enhanced cystine
      uptake following both PACAP and VIP treatment. These data introduce a novel
      mechanism by which both PACAP and VIP regulate system xc- activity. Synapse
      68:604-612, 2014. (c) 2014 Wiley Periodicals, Inc.

PMID- 25066645
TI  - The efficacy of oxygen wafting using different delivery devices, flow rates and
      device positioning.
AB  - BACKGROUND: Oxygen "wafting" provides a non-contact oxygen alternative for
      uncooperative paediatric patients in the emergency department (ED). The aim of
      this study was to identify the combination of oxygen delivery device, flow rate
      and device positioning that delivers the highest concentration of wafted oxygen.
      METHODS: ED nursing staff were surveyed to determine current oxygen wafting
      practice. A simulated patient and oxygen sensor were used to compare wafted
      oxygen concentrations for six delivery devices in various positions and oxygen
      flow rates. RESULTS: Only oxygen tubing and the paediatric non-rebreather mask
      consistently delivered wafted oxygen concentrations above 30%. The paediatric non
      rebreather held below the face produced concentrations ranging from 26.1% (10 cm)
      to 39.8% (5 cm). At 15 L/min, tubing held in front of the face produced
      concentrations ranging from 31.2% (15 cm) to 56.7% (5 cm); reducing the flow rate
      to 6-8 L/min had no meaningful effect on the delivered oxygen concentration. When
      tubing was used below the face, flow rates between 6 and 8 L/min produced
      somewhat higher concentrations than 15 L/min (5 cm: 36.3% vs. 30.9%).
      CONCLUSIONS: When delivering oxygen by wafting, the highest oxygen concentrations
      are achieved when positioning tubing 5-15 cm in front of the face or positioning
      tubing or a paediatric non-rebreather mask 5-10 cm below the face at 10-15 L/min
      flow. This should be considered when using oxygen wafting in the ED.

PMID- 25066646
TI  - Preliminary evaluation of dorsal muscle activity during resisted cervical
      extension in patients with longstanding pain and disability following anterior
      cervical decompression and fusion surgery.
AB  - OBJECTIVES: To compare mechanical activity (deformation and deformation rate) of
      the dorsal neck muscles between individuals with longstanding symptoms after
      anterior cervical decompression and fusion (ACDF) surgery and healthy controls.
      DESIGN: Preliminary cross-sectional study. SETTING: Neurosurgery clinic.
      PARTICIPANTS: Ten individuals {mean age 60 [standard deviation (SD) 7.1]} who had
      undergone ACDF surgery 10 to 13 years previously and 10 healthy age- and sex
      matched controls. MAIN OUTCOMES: Mechanical activity of the different layers of
      dorsal neck muscles, measured at the C4 segment using ultrasonography (speckle
      tracking analysis) during a standardised, resisted cervical extension task.
      RESULTS: A significant group*muscle interaction was found for muscle deformation
      (P<0.03) but not for deformation rate (P>0.79). The ACDF group showed
      significantly less deformation of the semispinalis capitis muscle during the
      extension task compared with the control group [mean 3.12 (SD 2.06) and 6.64 (SD
      4.17), respectively; mean difference 3.34 (95% confidence interval -0.54 to
      7.21)]. CONCLUSIONS: As the semispinalis capitis muscle is a powerful neck
      extensor, the finding of altered activation following ACDF surgery lends support
      to the inclusion of exercise to train neck muscle performance in the management
      of these patients.

PMID- 25066647
TI  - Dabigatran etexilate: An alternative to warfarin for patients with nonvalvular
      atrial fibrillation.
AB  - PURPOSE: To critically appraise the evidence on dabigatran etexilate, Pradaxa, as
      an alternative to warfarin for stroke prevention among patients with nonvalvular
      atrial fibrillation. This information can assist nurse practitioners in making
      informed treatment decisions. DATA SOURCES: A review of the literature was
      conducted using CINAHL and PubMed databases. Reports published on cardiovascular
      organizational web sites were also searched, along with reference lists of
      relevant published articles and reports. CONCLUSIONS: Significant evidence from
      the PETRO and RE-LY trials and postmarketing analyses of dabigatran etexilate
      indicate that this direct thrombin inhibitor is as efficacious as warfarin in
      ischemic stroke prevention. In fact, the studies found that patients taking
      dabigatran etexilate had fewer incidences of ischemic stroke and intracranial
      hemorrhage than those taking warfarin. Risk for major gastrointestinal bleeding
      appears to be higher than that for warfarin. IMPLICATIONS FOR PRACTICE: Patients
      taking dabigatran etexilate do not require blood work to assess international
      normalized ratio (INR) levels. Because this drug is excreted primarily by the
      kidneys, reassessment of renal function is critical during treatment, especially
      with concomitant use of diuretics, fluctuating renal function, or hypovolemia. As
      with warfarin, nurse practitioners should educate patients about when to seek
      immediate care for the development of anticoagulant-associated bleeding.

PMID- 25066648
TI  - Complex decongestive therapy and taping for patients with postmastectomy
      lymphedema: a randomized controlled study.
AB  - PURPOSE: The purpose of our study was to investigate the effects of Kinesio
      Taping((r)) Application with Complex Decongestive Therapy (CDT) in patients with
      lymphedema. MATERIALS AND METHODS: 45 patients were randomly divided into 3
      groups (CDT including Bandage, CDT including Bandage + Kinesio Tape((r)), CDT
      including Kinesio Tape((r)) without bandage). Assessments included the severity
      of the symptoms such as pain, discomfort, heaviness, tension, stiffness and
      weakness. Bilateral circumference measurements were done for evaluation of the
      edema. RESULTS: Symptoms were decreased in all three groups (p < 0.05). CDT was
      found effective only during treatment in arm volume (p < 0.05). Kinesio
      Taping((r)) applied with CDT had effect of decreasing edema after 10 days of
      treatment period (p < 0.05) and for control period (p < 0.05). Only the
      application of Kinesio Taping((r)) group also had significant decrease at edema
      (p < 0.05). CONCLUSION: Kinesio Taping((r)) Application along with CDT may have a
      better effect on decreasing lymphedema which can stimulate the reduction of edema
      for long term effects.

PMID- 25066649
TI  - The potential of adipokines as therapeutic agents for cardiovascular disease.
AB  - Adipose tissue functions as an endocrine organ by producing bioactive secretory
      proteins, also known as adipokines, that can directly act on nearby or remote
      organs. Most of the adipokines are upregulated by obese conditions, and typically
      promote obese complications. In contrast, some adipokines, such as adiponectin,
      CTRP9 and omentin, are downregulated in obese states. These factors exert
      salutary actions on obesity-linked cardiovascular disorders. In this review, we
      focus on the significance of adiponectin, CTRP9 and omentin as therapeutic agents
      for cardiovascular disease. 

PMID- 25066650
TI  - Psychometric testing on the NLN Student Satisfaction and Self-Confidence in
      Learning, Simulation Design Scale, and Educational Practices Questionnaire using
      a sample of pre-licensure novice nurses.
AB  - BACKGROUND: In 2006, the National League for Nursing published three measures
      related to novice nurses' beliefs about self-confidence, scenario design, and
      educational practices associated with simulation. Despite the extensive use of
      these measures, little is known about their reliability and validity. METHODS:
      The psychometric properties of the Student Satisfaction and Self-Confidence in
      Learning Scale, Simulation Design Scale, and Educational Practices Questionnaire
      were studied among a sample of 2200 surveys completed by novice nurses from a
      liberal arts university in the southern United States. Psychometric tests
      included item analysis, confirmatory and exploratory factor analyses in randomly
      split subsamples, concordant and discordant validity, and internal consistency.
      RESULTS: All three measures have sufficient reliability and validity to be used
      in education research. There is room for improvement in content validity with the
      Student Satisfaction and Self-Confidence in Learning and Simulation Design Scale.
      CONCLUSION: This work provides robust evidence to ensure that judgments made
      about self-confidence after simulation, simulation design and educational
      practices are valid and reliable.

PMID- 25066651
TI  - Effects of mindfulness-based stress reduction on depression, anxiety, stress and
      mindfulness in Korean nursing students.
AB  - BACKGROUND: Nursing students often experience depression, anxiety, stress and
      decreased mindfulness which may decrease their patient care effectiveness.
      Mindfulness-based stress reduction (MBSR) effectively reduced depression, anxiety
      and stress, and increased mindfulness in previous research with other
      populations, but there is sparse evidence regarding its effectiveness for nursing
      students in Korea. OBJECTIVES: To examine the effects of MBSR on depression,
      anxiety, stress and mindfulness in Korean nursing students. DESIGN: A randomized
      controlled trial. PARTICIPANTS/SETTING: Fifty (50) nursing students at KN
      University College of Nursing in South Korea were randomly assigned to two
      groups. Data from 44 students, MBSR (n=21) and a wait list (WL) control (n=23)
      were analyzed. METHODS: The MBSR group practiced mindfulness meditation for 2 h
      every week for 8 weeks. The WL group did not receive MBSR intervention.
      Standardized self-administered questionnaires of depression, anxiety, stress and
      mindfulness were administered at the baseline prior to the MBSR program and at
      completion (at 8 weeks). RESULTS: Compared with WL participants, MBSR
      participants reported significantly greater decreases in depression, anxiety and
      stress, and greater increase in mindfulness. CONCLUSION: A program of MBSR was
      effective when it was used with nursing students in reducing measures of
      depression, anxiety and stress, and increasing their mindful awareness. MBSR
      shows promise for use with nursing students to address their experience of mild
      depression, anxiety and stress, and to increase mindfulness in academic and
      clinical work, warranting further study.

PMID- 25066653
TI  - Whether taken medication can improve arterial stiffness or not.

PMID- 25066652
TI  - Experimental assessment of splicing variants using expression minigenes and
      comparison with in silico predictions.
AB  - Assessment of the functional consequences of variants near splice sites is a
      major challenge in the diagnostic laboratory. To address this issue, we created
      expression minigenes (EMGs) to determine the RNA and protein products generated
      by splice site variants (n = 10) implicated in cystic fibrosis (CF). Experimental
      results were compared with the splicing predictions of eight in silico tools.
      EMGs containing the full-length Cystic Fibrosis Transmembrane Conductance
      Regulator (CFTR) coding sequence and flanking intron sequences generated wild
      type transcript and fully processed protein in Human Embryonic Kidney (HEK293)
      and CF bronchial epithelial (CFBE41o-) cells. Quantification of variant induced
      aberrant mRNA isoforms was concordant using fragment analysis and pyrosequencing.
      The splicing patterns of c.1585-1G>A and c.2657+5G>A were comparable to those
      reported in primary cells from individuals bearing these variants. Bioinformatics
      predictions were consistent with experimental results for 9/10 variants (MES),
      8/10 variants (NNSplice), and 7/10 variants (SSAT and Sroogle). Programs that
      estimate the consequences of mis-splicing predicted 11/16 (HSF and ASSEDA) and
      10/16 (Fsplice and SplicePort) experimentally observed mRNA isoforms. EMGs
      provide a robust experimental approach for clinical interpretation of splice site
      variants and refinement of in silico tools.

PMID- 25066654
TI  - Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal
      disease.
AB  - OBJECTIVES: Gut microbiota provides beneficial effects under physiological
      conditions, but is able to contribute to inflammatory diseases in susceptible
      individuals. Thus, we designed this study to test whether additional intake of
      symbiotic gel affects specific modifications of gut microbiota in patients with
      end-stage renal disease (ESRD). METHODS: Eighteen patients with ESRD diagnosis
      with renal replacement therapy (hemodialysis) were included in this study. They
      were randomly assigned to 2 treatment groups: (1) test group (nutritional
      counseling + symbiotic) and (2) control group (nutritional counseling + placebo).
      Clinical history and the evaluation of Gastrointestinal Symptom Rating Scale were
      performed. Gut microbiota composition was analyzed by real-time polymerase chain
      reaction from fecal samples. All subjects were followed for 2 months. RESULTS:
      Bifidobacterial counts were higher in the second samples (mean: 5.5 +/- 1.72
      log10 cells/g) than in first samples (4.2 +/- 0.88 log 10 cells/g) in the
      patients of the test group (P = .0344). Also, lactobacilli counts had a little
      decrease in the test group (2.3 +/- 0.75 to 2.0 +/- 0.88 log 10 cells/g) and the
      control group (2.2 +/- 0.90 to 1.8 +/- 1.33 log 10 cells/g), between the first
      and the second samples. Gastrointestinal symptoms scores (scale 8-40) were
      reduced in the test group (start 12 [10-14] and end 9 [8-10]) compared with
      control group (start 11 [8-21] and end 11 [9-15]). CONCLUSIONS: Short-term
      symbiotic treatment in patients with ESRD can lead to the increase of
      Bifidobacterium counts, maintaining the intestinal microbial balance.

PMID- 25066656
TI  - Comparison of hydrogen elimination from molecular zinc and magnesium hydride
      clusters.
AB  - In analogy to the previously reported tetranuclear magnesium hydride cluster with
      a bridged dianionic bis-beta-diketiminate ligand, a related zinc hydride cluster
      has been prepared. The crystal structures of these magnesium and zinc hydride
      complexes are similar: the metal atoms are situated at the corners of a
      tetrahedron in which the vertices are bridged either by dianionic bis-beta
      diketiminate ligands or hydride ions. Both structures are retained in solution
      and show examples of H(-)???H(-) NMR coupling (Mg: 8.5 Hz; Zn: 16.0 Hz). The zinc
      hydride cluster [NN-(ZnH)2]2 thermally decomposes at 90  degrees C and releases
      1.8 equivalents of H2 . In contrast to magnesium hydride clusters, there is no
      apparent relationship between cluster size and thermal decomposition temperature
      for the zinc hydrides. DFT calculations reproduced the structure of the zinc
      hydride cluster reasonably well and charge density analysis showed no bond paths
      between the hydride ions. This contrasts with calculations on the analogous
      magnesium hydride cluster in which a counter-intuitive H(-)???H(-) bond path was
      observed. Forcing a reduced H(-)???H(-) distance in the zinc hydride cluster,
      however, gave rise to a H(-)???H(-) bond path. Such weak interactions could play
      a role in H2 desorption. The presumed molecular product after H2 release, a Zn(I)
      cluster, could not be characterized experimentally but DFT calculations predicted
      a cluster with two localized Zn-Zn bonds.

PMID- 25066655
TI  - Factors associated with tuberculosis by HIV status in the Brazilian national
      surveillance system: a cross sectional study.
AB  - BACKGROUND: Over the last decade tuberculosis (TB) incidence and mortality in
      Brazil have been steadily declining. However, this downward trend has not been
      observed among HIV-infected patients. We describe the epidemiological and
      clinical profile of TB patients by HIV status using the Brazilian National
      Surveillance System. METHODS: All TB diagnoses with HIV status information
      between January 1, 2007 and December 31, 2011 were categorized as either HIV or
      non-HIV at time of TB diagnosis. Co-infected patients (TB-HIV) were compared to
      TB patients with no HIV-infection using a hierarchical logistic regression model
      using Stata 13.0. RESULTS: The prevalence of TB-HIV co-infection was 19% among
      adults >= 15 years of age. We analyzed data from 243,676 individuals, of whom
      46,466 were TB-HIV and 197,210 were only TB cases. The following factors
      increased risk of co-infection: male sex (OR: 1.06, 95% CI 1.03-1.10), 20 to 39
      years of age (OR = 4.82, 95% CI 4.34-5.36), black (OR = 1.08, 95% CI 1.04-1.13),
      4-7 years of education (OR = 1.13, 95% CI 1.19-1.28), diagnosed following default
      (OR = 2.65, 95% CI 1.13-6.25), presenting with pulmonary and extra-pulmonary
      forms of TB simultaneously (OR = 2.80, 95% CI 1.56-5.02), presenting with
      histopathologic examination suggestive of TB (OR = 2.15, 95% CI 1.13-4.07). Co
      infected patients were less likely to live in rural areas (OR = 0.45, 95% CI 0.42
      0.48), have diabetes (OR = 0.45, 95% CI 0.40-0.50) and be smear positive (OR =
      0.55, 95% CI 0.32-0.95), and co-infected patients had higher risk of default (OR
      = 2.96, 95% CI 2.36-3.71) and death from TB (OR = 5.16, 95% CI 43.04-5.77).
      CONCLUSIONS: The prevalence of co-infection with HIV among TB patients is 19% in
      Brazil. By identifying predictors of co-infection targeted interventions can be
      developed to prevent both TB and HIV, and to diagnose each disease earlier and
      ultimately decrease poor treatment outcomes and death.

PMID- 25066657
TI  - N-N bond cleavage of 1,2-diarylhydrazines and N-H bond formation via H-atom
      transfer in vanadium complexes supported by a redox-active ligand.
AB  - Addition of stoichiometric quantites of 1,2-diarylhydrazines to the
      bis(imino)pyridine vanadium dinitrogen complex, [{((iPr)BPDI)V(THF)}2(MU2-N2)]
      ((iPr)BPDI = 2,6-(2,6-iPr2-C6H3N?CPh)2C5H3N), resulted in N-N bond cleavage to
      yield the corresponding vanadium bis(amido) derivatives, ((iPr)BPDI)V(NHAr)2 (Ar
      = Ph, Tol). Spectroscopic, structural, and computational studies support an
      assignment as vanadium(III) complexes with chelate radical anions, [BPDI](*-).
      With excess 1,2-diarylhydrazine, formation of the bis(imino)pyridine vanadium
      imide amide compounds, ((iPr)BPDI)V(NHAr)NAr, were observed along with the
      corresponding aryldiazene and aniline. A DFT-computed N-H bond dissociation free
      energy of 69.2 kcal/mol was obtained for ((iPr)BPDI)V(NHPh)NPh, and
      interconversion between this compound and ((iPr)BPDI)V(NHPh)2 with (2,2,6,6
      tetramethylpiperidin-1-yl)oxidanyl (TEMPO), 1,2-diphenylhydrazine, and xanthene
      experimentally bracketed this value between 67.1 and 73.3 kcal/mol. For
      ((iPr)BPDI)V(NHPh)2, the N-H BDFE was DFT-calculated to be 64.1 kcal/mol,
      consistent with experimental observations. Catalytic disproportionation of 1,2
      diarylhydrazines promoted by ((iPr)BPDI)V(NHAr)NAr was observed, and crossover
      experiments established exchange of anilide (but not imido) ligands in the
      presence of free hydrazine. These studies demonstrate the promising role of redox
      active active ligands in promoting N-N bond cleavage with concomitant N-H bond
      formation and how the electronic properties of the metal-ligand combination
      influence N-H bond dissocation free energies and related hydrogen atom transfer
      processes. 

PMID- 25066658
TI  - Photoisomerization and photooxygenation of 1,4-diaryl-1,3-dienes in a confined
      space.
AB  - Geometric isomerization of light-activated olefins plays a significant role in
      biological events as well as in modern materials science applications. In these
      systems, the isomerization occurs in highly confined spaces, and concepts derived
      from solution investigations are only partially applicable. This study makes
      contributions in understanding the excited-state behavior of olefins in confined
      spaces by investigating the excited-state behavior of 1,4-diphneyl-13-butadiene
      (DPB) and 1,4-ditolyl-1,3-butadiene (DTB) encapsulated in a well-defined organic
      capsule made up of the octa acid (OA) host. Both of these dienes that exist in
      three isomeric forms (trans,trans; trans,cis; and cis,cis) formed 1:2 guest-host
      complexes with OA in aqueous borate buffer. Competition experiments monitored by
      (1)H NMR signals revealed that among the three isomers the cis,cis isomer of DPB
      and DTB formed the most stable complex with OA. Molecular modeling studies
      suggested that all six isomers of DPB and DTB preferred the cisoid conformation
      within the OA capsule. Irradiation (>280 nm) of the diene-OA complex (diene@OA2)
      resulted in geometric isomerization, and the photostationary state consisted of
      cis,trans isomer as major and cis,cis as minor products. The photostationary
      state could be enriched with the cis,cis isomer in yields close to 70% with
      proper cutoff filters because the cis,cis isomer absorbs at shorter wavelength
      than the other two isomers. Consistent with the MD simulation prediction that
      trans,trans-DPB and trans,trans-DTB existed in cisoid conformation within OA
      capsule, the generation of singlet oxygen in the presence of OA encapsulated DPB
      or DTB resulted in facile [4 + 2] addition between the diene and the singlet
      oxygen. 

PMID- 25066659
TI  - The effects of functional fiber on postprandial glycemia, energy intake, satiety,
      palatability and gastrointestinal wellbeing: a randomized crossover trial.
AB  - BACKGROUND: Fiber intakes in developed countries are generally below those
      recommended by relevant authorities. Given that many people consume fiber
      depleted refined-grain products, adding functional fiber will help to increase
      fiber intakes. The objective of the study was to determine metabolic and sensory
      effects of adding fiber to bread. METHODS: A double-blind pair of randomized
      crossover trials with a two-week washout in which two fiber-containing breads
      were compared with control bread. The functional fiber (fruit fiber and FibreMax)
      was added to yield 10 g fiber per serve (two slices). Eighty participants (n = 37
      fruit fiber and n = 43 FibreMax) consumed one serve of bread (fiber or control)
      followed three hours later by a pasta meal consumed ad libitum. Outcome measures
      included glycemia, satiety, palatability, gastrointestinal wellbeing, visual
      appeal and subsequent energy intake of the pasta meal. Multivariate regression
      was undertaken to test for differences between treatment and control for blood
      glucose, satiety, and cumulative energy intake. Satiety responses were also
      compared by splitting the data into an immediate response after eating (0-30 min)
      and a return to hunger analysis (30-180 min). A Wilcoxon sign rank test was used
      for the first component (0-30 min) and Wilcoxon matched-pairs signed-rank test
      for the second component (30-180 min). Between treatment differences for
      gastrointestinal wellbeing were tested using Pearson's chi-square test or
      Fisher's exact test. RESULTS: Consumption of the fruit fiber bread reduced
      postprandial glycemia by 35% (95% CI 13 to 51; P = 0.004) and cumulative energy
      intake by 368 kJ (95% CI 163 to 531; P = 0.001). There was little influence on
      satiety and the bread was rated as having poor taste and smell whilst generating
      feelings of nausea in some participants. FibreMax enriched bread reduced glycemia
      by 43% (95% CI 17 to 61; P = 0.004) without influence on energy intake or
      satiety. Apart from a lower visual appeal, the FibreMax bread was palatable.
      Neither bread caused gastrointestinal discomfort related to flatulence or
      bloating. CONCLUSIONS: Enriching bread with 10 g of functional fiber per serve is
      feasible although reformulation is needed to create not only an acceptable bread,
      but a desirable product.

PMID- 25066660
TI  - Mental time travel in dysphoria: Differences in the content and subjective
      experience of past and future episodes.
AB  - Previous research has shown that depressed individuals demonstrate a number of
      biases in their ability to retrieve past events and simulate future events. The
      current study investigated the content and phenomenological experience of past
      and future events in dysphoric and non-dysphoric individuals. Results indicated
      that dysphoric, compared with non-dysphoric, individuals reported fewer positive
      events across both temporal directions. Furthermore, phenomenological
      characteristics ratings suggested that dysphoric individuals saw future, but not
      past, events as less vivid, coherent, sensorially detailed, bodily experienced,
      emotionally intense and important with respect to their life story and identity.
      These findings are discussed with reference to theories regarding the functions
      of 'mental time travel', in particular how the muted subjective experience of
      future episodes in depression may impair future planning, problem-solving and
      self regulation. 

PMID- 25066661
TI  - Inert fluorinated gas MRI: a new pulmonary imaging modality.
AB  - Fluorine-19 ((19)F) MRI of the lungs using inhaled inert fluorinated gases can
      potentially provide high quality images of the lungs that are similar in quality
      to those from hyperpolarized (HP) noble gas MRI. Inert fluorinated gases have the
      advantages of being nontoxic, abundant, and inexpensive compared with HP gases.
      Due to the high gyromagnetic ratio of (19)F, there is sufficient thermally
      polarized signal for imaging, and averaging within a single breath-hold is
      possible due to short longitudinal relaxation times. Therefore, the gases do not
      need to be hyperpolarized prior to their use in MRI. This eliminates the need for
      an expensive polarizer and expensive isotopes. Inert fluorinated gas MRI of the
      lungs has been previously demonstrated in animals, and more recently in healthy
      volunteers and patients with lung diseases. The ongoing improvements in image
      quality demonstrate the potential of (19)F MRI for visualizing the distribution
      of ventilation in human lungs and detecting functional biomarkers. In this brief
      review, the development of inert fluorinated gas MRI, current progress, and
      future prospects are discussed. The current state of HP noble gas MRI is also
      briefly discussed in order to provide context to the development of this new
      imaging modality. Overall, this may be a viable clinical imaging modality that
      can provide useful information for the diagnosis and management of chronic
      respiratory diseases.

PMID- 25066663
TI  - Evidence for structural and functional abnormality in the subgenual anterior
      cingulate cortex in major depressive disorder.
AB  - BACKGROUND: The subgenual anterior cingulate cortex (sgACC) is considered to be
      an important site of abnormality in major depressive disorder. However,
      structural alterations in this region have not been a consistent finding and
      functional imaging studies have also implicated additional areas. METHOD: A total
      of 32 patients with major depressive disorder, currently depressed, and 64
      controls underwent structural imaging with MRI. Also, 26 patients and 52 controls
      were examined using functional magnetic resonance imaging (fMRI) during
      performance of the n-back working memory task. Structural and functional changes
      were evaluated using whole-brain, voxel-based methods. RESULTS: The depressed
      patients showed volume reductions in the sgACC and orbitofrontal cortex
      bilaterally, plus in both temporal poles and the hippocampus/parahippocampal
      gyrus on the left. Functional imaging revealed task-related hypo-activation in
      the left lateral prefrontal cortex and other regions, as well as failure of
      deactivation in a subcallosal medial frontal cortical area which included the
      sgACC. CONCLUSIONS: Whole-brain, voxel-based analysis finds evidence of both
      structural and functional abnormality in the sgACC in major depressive disorder.
      The fact that the functional changes in this area took the form of failure of
      deactivation adds to previous findings of default mode network dysfunction in the
      disorder.

PMID- 25066665
TI  - Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male
      rats.
AB  - Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI
      (RTBI). TBI-induced hypopituitarism has been documented in both adults and
      juveniles and despite the necessity of pituitary function for normal physical and
      brain development, it is still unrecognized and untreated in adolescents
      following TBI. TBI induced hormonal dysfunction during a critical developmental
      window has the potential to cause long-term cognitive and behavioral deficits and
      the topic currently remains unaddressed. The purpose of this study was to
      determine if four mild TBIs delivered to adolescent male rats disrupts
      testosterone production and adult behavioral outcomes. Plasma testosterone was
      quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset,
      reproductive organ growth, erectile function and reproductive behaviors were
      assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic
      decreases in testosterone production and delayed onset of puberty. Significant
      deficits were observed in reproductive organ growth, erectile function and
      reproductive behaviors in adult rats at both 1 and 2 months postinjury. These
      data suggest adolescent RTBI-induced hypopituitarism underlies abnormal
      behavioral changes observed during adulthood. The impact of undiagnosed
      hypopituitarism following RTBI in adolescence has significance not only for
      growth and puberty, but also for brain development and neurobehavioral function
      as adults.

PMID- 25066666
TI  - Identification of predictive factors of response to the BH3-mimetic molecule ABT
      737: an ex vivo experiment in human serous ovarian carcinoma.
AB  - Ovarian cancers are addicted to Bcl-xL and Mcl-1, antiapoptotic members of the
      Bcl-2 family. Bcl-xL can be inhibited by the BH3-mimetic ABT-737. In vitro, ABT
      737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl
      1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes
      to ABT-737 when combined with carboplatin, which can indirectly inhibit Mcl-1.
      Fresh samples from 25 patients with high-grade serous ovarian cancer (HGSOC) who
      were chemo-naive and had undergone surgery were prospectively exposed ex vivo to
      ABT-737 +/- carboplatin. The treatment effect was studied on sliced tumor nodes
      by assessment of cleaved-caspase 3 immunostaining. We also studied the
      association between baseline Bcl-2 family protein expression (via
      immunohistochemistry) and the response of nodes to treatment. ABT-737 induced
      apoptosis as a single agent but its efficacy was not improved by the addition of
      carboplatin. Bim was frequently expressed (20/25) and its absence or low
      expression was associated with the absence of response to ABT-737, p value =
      0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66-100).
      Moreover, we observed that in tumors in which Bim was expressed, a low expression
      of phospho-Erk1/2 or Mcl-1 improved the proportion of responses. This pilot study
      showed that ABT-737 has promise as monotherapy for HGSOC in a specific subgroup
      of tumors. Bim, Mcl-1, and phospho-Erk1/2 appeared to be relevant biomarkers that
      could be used for the selection of patients in the design of clinical trials
      using Navitoclax (an orally available compound related to ABT-737).

PMID- 25066667
TI  - Vancomycin and piperacillin-tazobactam against methicillin-resistant
      Staphylococcus aureus and vancomycin-intermediate Staphylococcus aureus in an in
      vitro pharmacokinetic/pharmacodynamic model.
AB  - PURPOSE: Synergy between beta-lactams and vancomycin against methicillin
      resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate Staphylococcus
      aureus (VISA) has been observed in vitro and in vivo. However, studies
      investigating piperacillin-tazobactam with vancomycin against MRSA and VISA are
      limited despite broad clinical use of these antibiotics in combination. This
      study evaluated vancomycin and piperacillin-tazobactam against MRSA and VISA by
      using an in vitro pharmacokinetic/pharmacodynamic model. METHODS: Two clinical
      MRSA strains (M3425 and M494) and one VISA strain (Mu50) were tested in duplicate
      by using a 72-hour, 1-compartment pharmacokinetic/pharmacodynamic model with the
      following exposures: growth control, vancomycin only, piperacillin-tazobactam
      only, and vancomycin with piperacillin-tazobactam. Vancomycin 1 g every 12 hours
      (free trough concentration, 8.75 mg/L; Cmin, 17.5 mg/L) and piperacillin
      tazobactam 13.5 g per 24 hours' continuous infusion (free steady-state
      concentration, 27 mg/L) were simulated. Time-kill curves were constructed, and
      reductions in log10 CFU/mL at all time points were compared between regimens
      tested. FINDINGS: Vancomycin and piperacillin-tazobactam MICs for M494, M3425,
      and Mu50 were 1, 1, and 4 and 1.5, 32, and >256 mg/L, respectively. All isolates
      had an oxacillin MIC >= 4 mg/L. Against all 3 isolates, vancomycin with
      piperacillin-tazobactam achieved a significant reduction in inoculum at 72 hours
      compared with vancomycin alone (all, P <= 0.015). The superiority of vancomycin
      with piperacillin-tazobactam compared with vancomycin alone became detectable at
      8 hours for M3425 (P < 0.001) and at 24 hours for M494 and Mu50 (both, P <=
      0.008). Although vancomycin with piperacillin-tazobactam achieved enhanced
      antibacterial activity at 72 hours against M3425 compared with vancomycin alone,
      bacterial regrowth occurred. Reduced susceptibility to vancomycin at 72 hours for
      M3425 was confirmed by using population analysis profile/AUC analysis. At 72
      hours, M3425 had a PAP/AUC ratio of 0.77 compared to 0.51 at baseline.
      IMPLICATIONS: Vancomycin with piperacillin-tazobactam demonstrated enhanced
      antimicrobial activity against MRSA and VISA compared with vancomycin alone.
      These results further enhance existing data that support using vancomycin in
      combination with a beta-lactam for invasive MRSA infections. Combination therapy
      with vancomycin and a beta-lactam against MRSA warrants clinical consideration.

PMID- 25066668
TI  - Health economic evaluation of patients treated for nosocomial pneumonia caused by
      methicillin-resistant Staphylococcus aureus: secondary analysis of a multicenter
      randomized clinical trial of vancomycin and linezolid.
AB  - PURPOSE: Results from studies comparing health care resource use (HCRU), costs of
      treatment, and cost-effectiveness of linezolid compared with vancomycin therapy
      in the treatment of hospitalized patients with methicillin-resistant
      Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published
      literature. We therefore conducted an analysis to compare the HCRU, costs of
      treatment, and cost-effectiveness of linezolid compared with vancomycin in the
      treatment of hospitalized patients with MRSA nosocomial pneumonia using data from
      a Phase IV clinical trial. The economic effect of moderate to severe adverse
      events (MSAEs) and the development of renal failure were also evaluated. METHODS:
      We performed a post hoc analysis of data from a Phase IV, double-blind,
      randomized, comparator-controlled, multicenter trial that compared linezolid and
      vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs
      were compared based on treatment, development of MSAEs, and development of renal
      failure using data from the modified intent-to-treat population. Predictors of
      costs were evaluated using generalized linear models. A piggyback cost
      effectiveness analysis was conducted to assess the incremental cost-effectiveness
      ratio of linezolid versus vancomycin, given the significantly higher clinical
      success of linezolid compared with vancomycin found in the trial. FINDINGS:
      Overall, HCRU and costs were similar between the linezolid and vancomycin
      treatment groups; drug costs were significantly higher and dialysis costs
      significantly lower for linezolid- compared with vancomycin-treated patients.
      Total treatment costs were approximately $8000 higher (P = .046) for patients who
      developed renal failure compared with those who did not. Renal failure occurred
      more commonly in patients randomized to receive vancomycin (15%) compared with
      linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical
      failure, and development of renal failure were associated with significantly
      higher total costs. The point estimate incremental cost-effectiveness ratio for
      linezolid compared with vancomycin was $16,516 per treatment success, with
      linezolid dominant in 24% and dominated in <2% of bootstrapped samples.
      IMPLICATIONS: This phase 4 clinical trial conducted in patients with MRSA
      confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycin
      treated patients had similar HCRU and total overall costs. Fewer patients
      developed renal failure during the study while taking linezolid compared with
      vancomycin, and patients with a documented MSAE or renal failure had increased
      HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy
      in MRSA-confirmed nosocomial pneumonia.

PMID- 25066670
TI  - One-year follow up of PTSD and depression in elderly aboriginal people in Taiwan
      after Typhoon Morakot.
AB  - AIM: This paper describes a 1-year follow-up of post-traumatic stress disorder
      (PTSD) symptomatology and depression in an elderly minority population who
      experienced Typhoon Morakot in Taiwan. METHODS: The PTSD Symptom Scale--Interview
      and the 10-item short form Center for Epidemiological Studies Depression Scale
      were used to examine PTSD symptomatology and depression in 120 victims at 3-6
      months and in 88 victims (73.3% reinterview rate) at 11-12 months after the
      disaster. Further, we looked for associations between stress, prognosis, and
      development of PTSD symptomatology and depression. RESULTS: The prevalence of
      PTSD symptomatology decreased from 29.2% (35/120) at 3-6 months to 15.9% (14/88)
      at 11-12 months. The prevalence of depression, however, increased from 43.3%
      (52/120) to 46.6% (41/88). No factor was associated with follow-up PTSD
      symptomatology, and only the level of education was related to follow-up
      depression. Generally, the risk factors of age, sex, symptomatology of PTSD and
      depression at baseline, and stressor of unemployment predicted new-onset or
      chronic PTSD symptomatology and depression. Delayed-onset depression 48.0%
      (24/50) was more common than delayed-onset PTSD symptomatology 11.3% (7/62).
      Chronic and delayed-onset PTSD symptomatology were more easily developed with
      depression. CONCLUSION: Although PTSD and depression were separate consequences
      of trauma, they emerged and affected mental health together. We documented the
      courses of PTSD and depression among elderly aboriginal people, and the possible
      effects of demographic, symptomatology, and adverse life stressors were
      discussed.

PMID- 25066669
TI  - The acute effects of daily nicotine intake on heart rate--a toxicokinetic and
      toxicodynamic modelling study.
AB  - Joint physiologically-based toxicokinetic and toxicodynamic (PBTK/TD) modelling
      was applied to simulate concentration-time profiles of nicotine, a well-known
      stimulant, in the human body following single and repeated dosing. Both kinetic
      and dynamic models were first calibrated by using in vivo literature data for the
      Caucasian population. The models were then used to estimate the blood and liver
      concentrations of nicotine in terms of the Area Under Curve (AUC) and the peak
      concentration (Cmax) for selected exposure scenarios based on inhalation
      (cigarette smoking), oral intake (nicotine lozenges) and dermal absorption
      (nicotine patches). The model simulations indicated that whereas frequent
      cigarette smoking gives rise to high AUC and Cmax in blood, the use of nicotine
      rich dermal patches leads to high AUC and Cmax in the liver. Venous blood
      concentrations were used to estimate one of the most common acute effects, mean
      heart rate, both at rest and during exercise. These estimations showed that
      cigarette smoking causes a high peak heart rate, whereas dermal absorption causes
      a high mean heart rate over 48h. This study illustrates the potential of using
      PBTK/TD modelling in the safety assessment of nicotine-containing products. 

PMID- 25066671
TI  - Non-invasive assessment of cutaneous wound healing using fluorescent imaging.
AB  - BACKGROUND/PURPOSE: Optical imaging is a very important technique in the
      biomedical sciences. The purpose of this study was to develop an in vivo optical
      system for fluorescent imaging and molecular imaging applications using quantum
      dots (QDs). METHODS: The in vivo optical system was composed of modular parts,
      including a light source, light guide, excitation filter wheel, excitation
      filters, emission filter wheel, emission filters, liquid crystal tunable filter
      (LCTF), macro lens, dark chamber, and a cooled charged-coupled device (CCD)
      camera for recording images. Filters were selected based on the excitation and
      absorption spectra of QDs to allow spectral separation and optimization of the
      acquired image. In contrast with conventional systems, our system allows
      selection of the emission bandwidth. RESULTS: The system was tested in an in vivo
      study using a wound-healing model in nude mice. The healing process was examined
      after injection of fibroblasts and keratinocytes labeled with two different sets
      of QDs. The different QD probes were readily detected and distinguished using our
      system. CONCLUSION: An in vivo optical system is a very useful tool for the
      detection of genes, proteins, and small-molecule drugs inside living animals, and
      this imaging modality can also be adopted for real-time visualization of cancer
      cell metastasis in live animals.

PMID- 25066672
TI  - Floral primordia-targeted ACS (1-aminocyclopropane-1-carboxylate synthase)
      expression in transgenic Cucumis melo implicates fine tuning of ethylene
      production mediating unisexual flower development.
AB  - MAIN CONCLUSION: Floral primordia-targeted expression of the ethylene
      biosynthetic gene, ACS , in melon suggests that differential timing and ethylene
      response thresholds combine to promote carpels, inhibit stamens, and prevent
      asexual bud formation. Typical angiosperm flowers produce both male and female
      reproductive organs. However, numerous species have evolved unisexuality. Melons
      (Cucumis melo L.) can produce varying combinations of male, female or bisexual
      flowers. Regardless of final sex, floral development begins with sequential
      initiation of all four floral whorls; unisexuality results from carpel or stamen
      primordia arrest regulated by the G and A loci, respectively. Ethylene, which
      promotes femaleness, is a key factor regulating sex expression. We sought to
      further understand the location, timing, level, and relationship to sex gene
      expression required for ethylene to promote carpel development or inhibit stamen
      development. Andromonoecious melons (GGaa) were transformed with the ethylene
      biosynthetic enzyme gene, ACS (1-aminocyclopropane-1-carboxylate synthase),
      targeted for expression in stamen and petal, or carpel and nectary, primordia
      using Arabidopsis APETALA3 (AP3) or CRABSCLAW (CRC) promoters, respectively.
      CRC::ACS plants did not exhibit altered sex phenotype. AP3::ACS melons showed
      increased femaleness manifested by gain of a bisexual-only phase not seen in wild
      type, decreased male buds and flowers, and loss of the initial male-only phase.
      In extreme cases, plants became phenotypically hermaphrodite, rather than
      andromonoecious. A reduced portion of buds progressed beyond initial whorl
      formation. Both the ACS transgene and exogenous ethylene reduced the expression
      of the native carpel-suppressing gene, G, while elevating expression of the
      stamen-suppressing gene, A. These results show ethylene-mediated regulation of
      key sex expression genes and suggest a mechanism by which temporally regulated
      ethylene production and differential ethylene response thresholds can promote
      carpels, inhibit stamens, and prevent the formation of asexual buds.

PMID- 25066673
TI  - Evaluation of yolk protein levels as estrogenic biomarker in bivalves; comparison
      of the alkali-labile phosphate method (ALP) and a species-specific immunoassay
      (ELISA).
AB  - Altered concentration of the vertebrate yolk protein precursor vitellogenin is a
      recognized biomarker for endocrine disruption in fish, and within recent years
      yolk protein alteration has also been associated with endocrine disruption in
      bivalves. Species-specific, direct and sensitive methods for quantification of
      vitellogenin in fish have been available for years whereas bivalve yolk protein
      levels have been estimated indirectly by alkali-labile phosphate (ALP) liberated
      from high molecular weight proteins because the sequence and biochemical
      structure of most bivalve yolk proteins are unknown. By applying a species
      specific enzyme-linked immunosorbent assay (ELISA) for accurate determination of
      yolk protein level the impact of 17beta-estradiol (57, 164 and 512 ng/L) on the
      freshwater bivalve Unio tumidus was investigated and compared with ALP
      estimations. Seven weeks of exposure during the pre-spawning and spawning period
      had no consistent effect on yolk protein concentration in hemolymph, and ALP
      levels in hemolymph also remained unchanged in both males and females. Further,
      basal male and female ALP levels were indistinguishable whereas the ELISA
      demonstrated that yolk protein levels of females exceeded male levels at the time
      of sampling, although male basal levels were high compared to fish. Altogether it
      is shown that individual ALP levels do not reflect yolk protein levels and hence
      hemolymph ALP levels cannot serve as biomarker for estrogenic exposure during the
      pre-spawning and spawning period in U. tumidus. The necessity of sensitive and
      validated biomarkers for reliable interpretation of data and the utility of ALP
      and yolk protein levels as biomarkers in bivalves are discussed.

PMID- 25066674
TI  - Calcium signaling in cilia and ciliary-mediated intracellular calcium signaling:
      are they independent or coordinated molecular events?

PMID- 25066675
TI  - Endocrine disruptors and other inhibitors of 11beta-hydroxysteroid dehydrogenase
      1 and 2: Tissue-specific consequences of enzyme inhibition.
AB  - Numerous chemicals in the environment have the ability to interact with the
      endocrine system. These compounds are called endocrine disruptors (EDs). Exposure
      to EDs represents one of the hypotheses for decreasing fertility, the increased
      risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes.
      There are various mechanisms of ED action, one of which is their interference in
      the action of 11beta-hydroxysteroid dehydrogenase (11betaHSD) that maintains a
      balance between active and inactive glucocorticoids on the intracellular level.
      This enzyme has two isoforms and is expressed in various tissues. Inhibition of
      11betaHSD in various tissues can have different consequences. In the case of EDs,
      the results of exposure are mainly adverse; on the other hand pharmaceutically
      developed inhibitors of 11betaHSD type 1 are evaluated as an option for treating
      metabolic syndrome, as well as related diseases and depressive disorders. This
      review focuses on the effects of 11betaHSD inhibitors in the testis, colon,
      adipose tissue, kidney, brain and placenta. 

PMID- 25066676
TI  - Safety and clinical activity of 5-aza-2'-deoxycytidine (decitabine) with or
      without Hyper-CVAD in relapsed/refractory acute lymphocytic leukaemia.
AB  - To test the safety and activity of 5-aza-2'-deoxycytidine (decitabine) in
      patients with relapsed/refractory acute lymphocytic leukaemia (ALL), we conducted
      a phase 1 study with two parts: administering decitabine alone or in combination
      with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin and
      dexamethasone alternating with high-dose methotrexate and cytarabine). Patients
      participated in either part of the study or in both parts sequentially. In the
      initial part, decitabine was administered intravenously at doses of 10-120
      mg/m(2) per d for 5 d every other week in cycles of 28 d. In the combination
      part, patients were treated on the first 5 d of Hyper-CVAD with intravenous
      decitabine at 5-60 mg/m(2) per d. A total of 39 patients received treatment in
      the study: 14 in the first part only, 16 sequentially in both parts and 9 in the
      second part only. Decitabine was tolerated at all doses administered, and grade 3
      or 4 toxic effects included non-life-threatening hepatotoxicity and
      hyperglycaemia. Induction of DNA hypomethylation was observed at doses of
      decitabine up to 80 mg/m(2) . Some patients who had previously progressed on
      Hyper-CVAD alone achieved a complete response when decitabine was added.
      Decitabine alone or given with Hyper-CVAD is safe and has clinical activity in
      patients with advanced ALL.

PMID- 25066683
TI  - Morphology and phylogeny of three trachelocercid ciliates, with description of a
      new species, Trachelocerca orientalis spec. nov. (Ciliophora, Karyorelictea).
AB  - Three trachelocercid ciliates, Trachelocerca orientalis spec. nov.,
      Prototrachelocerca fasciolata (Sauerbrey, 1928) Foissner, 1996 and Tracheloraphis
      huangi Xu et al., 2011, isolated from marine coastal habitats at Qingdao, China,
      were taxonomically studied using observation in vivo and silver staining methods.
      The new species T. orientalis spec. nov. can be recognized by the combination of
      its size (600-1,200 MUm in vivo), 15-21 somatic kineties and about 13 groups of
      macronuclear nodules forming a strand and the colorless globular cortical
      granules. Together with the sequence data of the small subunit ribosomal RNA (SSU
      rRNA) gene, the information of a new isolate of P. fasciolata and three
      populations of T. huangi is also documented based on the present work. According
      to the molecular data, the phylogeny of three species is estimated and the
      analyses show that they are all found within the trachelocercid assemblage though
      T. huangi does not cluster with its congeners but with Trachelocerca species.
      Nonetheless, the monophyly of Trachelocerca is not rejected by the approximately
      unbiased test (p = 0.345 > 0.05), while that of Tracheloraphis is not confirmed
      (p = 0.0002 < 0.05).

PMID- 25066684
TI  - The causes of parent-offspring transmission of drug abuse: a Swedish population
      based study.
AB  - BACKGROUND: While drug abuse (DA) is strongly familial, we still have limited
      knowledge about the causes of its cross-generational transmission. METHOD: We
      examined DA ascertained from national registers in offspring of three family
      types from the Swedish population [intact (n = 2,111,074), 'not-lived-with' (n =
      165,315, where biological parents never lived with their offspring) and 'step' (n
      = 124,800 offspring)], which reflected, respectively, the effects of genes +
      rearing, genes only and rearing only. We replicated these results in three high
      risk co-relative designs. RESULTS: Combined across mothers and fathers, the
      hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact,
      2.73 in 'not-lived-with' and 1.79 in stepfamilies. In 968 biological full or half
      sibling pairs one of whom was reared by and the other never lived with their
      parent with DA, the HR for DA was greater in the reared than 'not-lived-with'
      child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was
      greater in a reared biological v. step-parented non-biological child (HR 3.33).
      In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with
      biological child and the second a step-parented non-biological child, the HR for
      DA was greater in the biological v. stepchild (HR 1.80). CONCLUSIONS: Both
      genetic and environmental factors contribute substantially to parent-offspring
      resemblance for DA. The general population contains informative family
      constellations that can complement more traditional adoption designs in
      clarifying the sources of parent-offspring resemblance.

PMID- 25066685
TI  - Greater collagen-induced platelet aggregation following cyclooxygenase 1
      inhibition predicts incident acute coronary syndromes.
AB  - Greater ex vivo platelet aggregation to agonists may identify individuals at risk
      of acute coronary syndromes (ACS). However, increased aggregation to a specific
      agonist may be masked by inherent variability in other activation pathways. In
      this study, we inhibited the cyclooxygenase-1 (COX1) pathway with 2-week aspirin
      therapy and measured residual aggregation to collagen and ADP to determine
      whether increased aggregation in a non-COX1 pathway is associated with incident
      ACS. We assessed ex vivo whole blood platelet aggregation in 1,699 healthy
      individuals with a family history of early-onset coronary artery disease followed
      for 6+/-1.2 years. Incident ACS events were observed in 22 subjects. Baseline
      aggregation was not associated with ACS. After COX1 pathway inhibition, collagen
      induced aggregation was significantly greater in participants with ACS compared
      with those without (29.0 vs. 23.6 ohms, p < 0.001). In Cox proportional hazards
      models, this association remained significant after adjusting for traditional
      cardiovascular risk factors (HR = 1.10, 95%CI = 1.06-1.15; p < 0.001). In
      contrast, ADP-induced aggregation after COX1 inhibition was not associated with
      ACS. After COX1 pathway inhibition, subjects with greater collagen-induced
      platelet aggregation demonstrated a significant excess risk of incident ACS.
      These data suggest that platelet activation related to collagen may play an
      important role in the risk of ACS. 

PMID- 25066686
TI  - [For your eyes only: Ian Fleming (1908-1964)].

PMID- 25066687
TI  - Pulmonary vein isolation with a new multipolar irrigated radiofrequency ablation
      catheter (nMARQTM): feasibility, acute and short-term efficacy, safety, and
      impact on postablation silent cerebral ischemia.
AB  - BACKGROUND: Simultaneous multipolar ablation catheters have been proposed to
      simplify pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (AF).
      Recently, a new multipolar irrigated radiofrequency (RF) ablation catheter
      (nMARQTM, Biosense Webster Inc., Diamond Bar, CA, USA) combining both 3
      dimensional electroanatomic mapping and multipolar open-irrigated ablation
      capability has been developed. Aim of our study was to assess feasibility, acute
      and short-term success and safety of PVI by the use of this new technology with
      particular regard to the incidence of postablation silent cerebral ischemia
      (SCI). METHODS AND RESULTS: Twenty-five patients (76% males; age 57 +/- 13 years)
      with paroxysmal AF underwent PVI using the nMARQTM catheter. PVI, confirmed by
      Lasso catheter mapping, was achieved in 100 out of 102 pulmonary veins (98%)
      identified, and final PVI was obtained in 24 out of 25 (96%) patients. The
      overall concordance between Lasso and nMARQTM signals in demonstrating PVI was
      78%. No major procedural complications occurred and no patient suffered SCI, on
      the basis of cerebral magnetic resonance imaging performed before and after the
      procedure. Following a 6-month follow-up, 17/25 (68%) patients remained free from
      AF without antiarrhythmic drugs. CONCLUSIONS: In our preliminary experience, PVI
      with nMARQTM catheter appears to be feasible and safe, without incidence of SCI.
      Long-term clinical efficacy has to be evaluated in further studies.

PMID- 25066688
TI  - Rubella and pregnancy: diagnosis, management and outcomes.
AB  - Rubella is a mild viral disease that typically occurs in childhood. Rubella
      infection during pregnancy causes congenital rubella syndrome, including the
      classic triad of cataracts, cardiac abnormalities and sensorineural deafness.
      Highly effective vaccines have been developed since 1969, and vaccination
      campaigns have been established in many countries. Although there has been
      progress, the prevention and diagnosis of rubella remain problematic. This
      article reviews the implications and management of rubella during pregnancy.

PMID- 25066689
TI  - Decision making in young people at familial risk of depression.
AB  - BACKGROUND: Major depression is associated with abnormalities in reward
      processing at neural and behavioural levels. Neural abnormalities in reward have
      been described in young people at familial risk of depression but behavioural
      changes in reward-based decision making have been less studied in this group.
      METHOD: We studied 63 young people (mean age 18.9 years) with a parent with a
      diagnosis of major depression but who had never been depressed themselves, that
      is with a positive family history of depression (the FH+ group). Participants
      performed the Cambridge Gambling Task (CGT), which provides several measures of
      decision making including deliberation time, quality of decision making, risk
      taking, risk adjustment and delay aversion. A control group of 49 age- and gender
      matched young people with no history of mood disorder in a first-degree relative
      undertook the same task. RESULTS: Both FH+ participants and controls had low and
      equivalent scores on anxiety and depression self-rating scales. Compared to
      controls, the FH+ participants showed overall lower risk taking, although like
      controls they made more risky choices as the odds of a favourable outcome
      increased. No other measures of decision making differed between the two groups.
      CONCLUSIONS: Young people at increased familial risk of depression have altered
      risk taking that is not accounted for by current affective symptomatology.
      Lowered risk taking might represent an impairment in reward seeking, which is one
      of several changes in reward-based behaviours seen in acutely depressed patients;
      however, our findings suggest that decreased reward seeking could be part of a
      risk endophenotype for depression.

PMID- 25066690
TI  - Prevalence of hyperglycaemia in singleton versus twin pregnancy.
AB  - BACKGROUND: There is conflicting information regarding the risk of gestational
      diabetes mellitus in twin pregnancies. This study was conducted to determine
      whether the risk of gestational diabetes mellitus is higher in pregnant Japanese
      women with twin versus singleton pregnancy. METHODS: The prevalence of
      gestational diabetes mellitus was studied in two different populations: 144 589
      women registered with the Japan Society of Obstetrics and Gynecology (JSOG
      cohort) over 3 years between 2007 and 2009 in which patient selection bias was
      unavoidable; and 430 Japanese women who gave birth at a single centre over 5
      years between 2008 and 2012 (single-centre cohort), consisting of 86 women with
      twins and 344 women with singletons matched for maternal age and prepregnancy
      body mass index. The gestational diabetes mellitus was diagnosed on the basis of
      the previous criteria in the JSOG cohort. The gestational diabetes mellitus was
      screened in a stepwise method and diagnosed on the basis of the new criteria in
      the single-centre cohort. RESULTS: In the single-centre cohort, neither frequency
      of random glucose level >=105 mg/dL in the first trimester [9.0% (31/344) vs 5.8%
      (5/86)], positive result (>=140 mg/dL) on 50 g glucose challenge test in the
      second trimester [26.5% (90/339) vs 26.7% (23/86)], nor women diagnosed with GDM
      [8.4% (29/344) vs 9.3% (8/86)] differed between the two groups. The prevalence of
      hyperglycaemia was higher in singleton than in twin pregnancies in the JSOG
      cohort (2.6% vs 1.8%, p < 0.001). CONCLUSIONS: The risk of gestational diabetes
      mellitus may be similar between Japanese women with singleton and twin
      pregnancies. Difference in the risk of hyperglycaemia in the JSOG cohort may have
      been due to selection bias.

PMID- 25066691
TI  - Impairment in circadian activity rhythms occurs during dexamethasone therapy in
      children with leukemia.
AB  - BACKGROUND: Circadian rhythm disturbances in adults with cancer are associated
      with fatigue, time to relapse, and death. This study of circadian activity
      rhythms (CAR) of children with acute lymphoblastic leukemia (ALL) on continuation
      chemotherapy aimed to describe CAR before and after starting dexamethasone, and
      to determine whether fatigue was associated with less robust CAR. PROCEDURE: This
      was a secondary analysis of data from a multi-institutional study in which
      children with ALL aged 5-18 years wore an actigraph for 10 consecutive 24-hour
      periods, five before and five during dexamethasone therapy. CAR parameters
      measured by actigraphy were calculated for each 5-day period, including peak
      activity, MESOR, amplitude, acrophase, and circadian quotient. Fatigue was
      measured on study days 2, 5, 7, and 10 by parent-report and self-report for
      children >= 7 years. RESULTS: Eighty-two children qualified for CAR analysis, and
      87 for analysis of daily peak activity patterns and fatigue. Mean age was 8.8 +/-
      3.3 years. Peak activity, MESOR, and amplitude significantly decreased during
      dexamethasone therapy. Children on high-dose dexamethasone (8 or 12 mg/m(2)/d)
      had significantly higher (better, or more robust) values of several CAR
      parameters than those on low-dose (6 mg/m(2)/d). There was a significant trend of
      decreasing daily pattern of peak activity during dexamethasone therapy only.
      Fatigue increased across the study and was associated with decreasing CAR peak
      activity, MESOR, and amplitude. CONCLUSIONS: Dexamethasone initiation was
      associated with a decrease in several CAR parameters, and a significant decrease
      in the trend of daily peak activity. Fatigue was associated with less robust CAR.

PMID- 25066692
TI  - Roles for chemokines in liver disease.
AB  - Sustained hepatic inflammation is an important factor in progression of chronic
      liver diseases, including hepatitis C or non-alcoholic steatohepatitis. Liver
      inflammation is regulated by chemokines, which regulate the migration and
      activities of hepatocytes, Kupffer cells, hepatic stellate cells, endothelial
      cells, and circulating immune cells. However, the effects of the different
      chemokines and their receptors vary during pathogenesis of different liver
      diseases. During development of chronic viral hepatitis, CCL5 and CXCL10 regulate
      the cytopathic versus antiviral immune responses of T cells and natural killer
      cells. During development of nonalcoholic steatohepatitis, CCL2 and its receptor
      are up-regulated in the liver, where they promote macrophage accumulation,
      inflammation, fibrosis, and steatosis, as well as in adipose tissue. CCL2
      signaling thereby links hepatic and systemic inflammation related to metabolic
      disorders and insulin resistance. Several chemokine signaling pathways also
      promote hepatic fibrosis. Recent studies have shown that other chemokines and
      immune cells have anti-inflammatory and antifibrotic activities. Chemokines and
      their receptors can also contribute to the pathogenesis of hepatocellular
      carcinoma, promoting proliferation of cancer cells, the inflammatory
      microenvironment of the tumor, evasion of the immune response, and angiogenesis.
      We review the roles of different chemokines in the pathogenesis of liver diseases
      and their potential use as biomarkers or therapeutic targets. 

PMID- 25066693
TI  - The role of impulsivity in dropout from treatment for cigarette smoking.
AB  - Impulsivity is a variable that has been associated with drug use. This study
      analyzes impulsivity from two different paradigms, one considering it as a trait
      and the other based on its behavioral correlates, such as disinhibition and
      impulsive decision-making in the treatment prognosis (maintain abstinence,
      relapse and dropout) of smokers after outpatient treatment. The participants in
      the study were 113 smokers who requested treatment for nicotine addiction. They
      were assigned to three groups according to whether or not they remained abstinent
      one month after beginning treatment; thus, group 1 was abstinent, group 2 had
      relapsed, and group 3 had dropped out of treatment. The participants filled out
      the Semi-structured Interview for Smokers, the Fargerstrom Test for Nicotine
      Dependence, the Temperament and Character Inventory-Revised (TCI-R) and the Delay
      Discounting Task (DDT). The Delay Discounting variable presents lower scores in
      the dropout group than in the relapse and abstinent groups, with the highest
      scores in the relapse group. Differences were also found on the Harm Avoidance
      (HA) variable, with lower scores in the dropout group compared to the relapse
      group. The importance of these results lies in the consideration of the smoker's
      personality profile in order to prevent both dropout and relapse. 

PMID- 25066695
TI  - beta-Blocker carvedilol protects cardiomyocytes against oxidative stress-induced
      apoptosis by up-regulating miR-133 expression.
AB  - Oxidative stress is a causal factor and key promoter of a variety of
      cardiovascular diseases associated with apoptotic cell death by causing
      deregulation of related genes. Though carvedilol, a beta-adrenergic blocker, has
      been shown to produce cytoprotective effects against cardiomyocyte apoptosis, the
      mechanisms are not fully understood. The present study was designed to
      investigate whether the beneficial effects of carvedilol are related to microRNAs
      which have emerged as critical players in cardiovascular pathophysiology via post
      transcriptional regulation of protein-coding genes. In vivo, we demonstrated that
      carvedilol ameliorated impaired cardiac function of infarct rats and restored miR
      133 expression. In vitro, carvedilol protected cardiomyocytes from H2O2 induced
      apoptosis detected by TUNEL staining and MTT assays, and increased miR-133
      expression in cardiomyocytes. Overexpression of miR-133, a recognized anti
      apoptotic miRNA, produced similar effects to carvedilol: reduction of reactive
      oxygen species (ROS) and malondialdehyde (MDA) content and increment of
      superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) level, so as
      to protect cardiomyocytes from apoptosis by downregulating caspase-9 and caspase
      3 expression in the presence of H2O2. Transfection with AMO-133 (antisense
      inhibitor oligodeoxyribonucleotides) alone abolished the beneficial effects of
      carvedilol. Caspase-9-specific inhibitor z-LEHD-fmk, caspase-3-specific inhibitor
      z-DEVD-fmk, caspase-9 siRNA and caspase-3 siRNA were used to establish caspase-3
      as a downstream target of miR-133. In conclusion, our data indicated that
      carvedilol protected cardiomyocytes by increasing miR-133 expression and
      suppressing caspase-9 and subsequent apoptotic pathways. 

PMID- 25066694
TI  - Netrin-1 abrogates ischemia/reperfusion-induced cardiac mitochondrial dysfunction
      via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS.
AB  - Despite an established role of mitochondrial dysfunction in cardiac
      ischemia/reperfusion (I/R) injury, the upstream activators have remained
      incompletely defined. We have recently identified an innovative role of
      exogenously applied netrin-1 in cardioprotection, which is mediated by increased
      nitric oxide (NO) bioavailability. Here, we tested the hypothesis that this
      "pharmacological" treatment of netrin-1 preserves mitochondrial function via
      novel mechanisms that are NO dependent. Freshly isolated C57BL6 mouse hearts were
      perfused using a Langendorff system, and subjected to a 20min global
      ischemia/60min reperfusion, in the presence or absence of netrin-1. I/R induced
      marked increases in infarct size, total superoxide and hydrogen peroxide
      production, activity and protein abundance of NADPH oxidase (NOX) isoform 4
      (NOX4), as well as impaired mitochondrial integrity and function, all of which
      were attenuated by netrin-1. This protective effect of netrin-1 is attributed to
      cGMP, a downstream effector of NO. The protein levels of NOX1 and NOX2 were
      however unaffected, and infarct size from NOX1 and NOX2 knockouts was not
      different from wild type animals. Scavenging of NO with PTIO reversed inhibitory
      effects of netrin-1 on NOX4, while NO donor attenuated NOX4 protein abundance. In
      vivo NOX4 RNAi, or sepiapterin perfusion, resulted in recoupling of NOS,
      decreased infarct size, and blockade of dysfunctional mitochondrial swelling and
      mitochondrial superoxide production. These data demonstrate that netrin-1 induces
      cardioprotection through inhibition of NOX4 activity, which leads to recoupling
      of NOS, augmented NO bioavailability, reduction in oxidative stress, and
      ultimately preservation of mitochondrial function. The NO-dependent NOX4
      inhibition connects with our previously established pathway of
      DCC/ERK1/2/eNOS/NO/DCC feed-forward mechanism, to maintain NOS in the coupling
      state to attenuate oxidative stress to preserve mitochondrial function. These
      findings may promote development of novel therapeutics for cardiac I/R injury.
      This article is part of a Special Issue entitled "Mitochondria: From Basic
      Mitochondrial Biology to Cardiovascular Disease".

PMID- 25066696
TI  - Cardiac dysfunction and peri-weaning mortality in malonyl-coenzyme A
      decarboxylase (MCD) knockout mice as a consequence of restricting substrate
      plasticity.
AB  - Inhibition of malonyl-coenzyme A decarboxylase (MCD) shifts metabolism from fatty
      acid towards glucose oxidation, which has therapeutic potential for obesity and
      myocardial ischemic injury. However, ~40% of patients with MCD deficiency are
      diagnosed with cardiomyopathy during infancy. AIM: To clarify the link between
      MCD deficiency and cardiac dysfunction in early life and to determine the
      contributing systemic and cardiac metabolic perturbations. METHODS AND RESULTS:
      MCD knockout mice ((-/-)) exhibited non-Mendelian genotype ratios (31% fewer MCD(
      /-)) with deaths clustered around weaning. Immediately prior to weaning (18days)
      MCD(-/-) mice had lower body weights, elevated body fat, hepatic steatosis and
      glycogen depletion compared to wild-type littermates. MCD(-/-) plasma was
      hyperketonemic, hyperlipidemic, had 60% lower lactate levels and markers of
      cellular damage were elevated. MCD(-/-) hearts exhibited hypertrophy, impaired
      ejection fraction and were energetically compromised (32% lower total adenine
      nucleotide pool). However differences between WT and MCD(-/-) converged with age,
      suggesting that, in surviving MCD(-/-) mice, early cardiac dysfunction resolves
      over time. These observations were corroborated by in silico modelling of
      cardiomyocyte metabolism, which indicated improvement of the MCD(-/-) metabolic
      phenotype and improved cardiac efficiency when switched from a high-fat diet
      (representative of suckling) to a standard post-weaning diet, independent of any
      developmental changes. CONCLUSIONS: MCD(-/-) mice consistently exhibited cardiac
      dysfunction and severe metabolic perturbations while on a high-fat, low
      carbohydrate diet of maternal milk and these gradually resolved post-weaning.
      This suggests that dysfunction is a common feature of MCD deficiency during early
      development, but that severity is dependent on composition of dietary substrates.

PMID- 25066697
TI  - Sex differences in SR Ca(2+) release in murine ventricular myocytes are regulated
      by the cAMP/PKA pathway.
AB  - Previous studies have shown that ventricular myocytes from female rats have
      smaller contractions and Ca(2+) transients than males. As cardiac contraction is
      regulated by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)
      pathway, we hypothesized that sex differences in cAMP contribute to differences
      in Ca(2+) handling. Ca(2+) transients (fura-2) and ionic currents were measured
      simultaneously (37 degrees C, 2Hz) in ventricular myocytes from adult male and
      female C57BL/6 mice. Under basal conditions, diastolic Ca(2+), sarcoplasmic
      reticulum (SR) Ca(2+) stores, and L-type Ca(2+) current did not differ between
      the sexes. However, female myocytes had smaller Ca(2+) transients (26% smaller),
      Ca(2+) sparks (6% smaller), and excitation-contraction coupling gain in
      comparison to males (23% smaller). Interestingly, basal levels of intracellular
      cAMP were lower in female myocytes (0.7+/-0.1 vs. 1.7+/-0.2fmol/MUg protein;
      p<0.001). Importantly, PKA inhibition (2MUM H-89) eliminated male-female
      differences in Ca(2+) transients and gain, as well as Ca(2+) spark amplitude.
      Western blots showed that PKA inhibition also reduced the ratio of phospho:total
      RyR2 in male hearts, but not in female hearts. Stimulation of cAMP production
      with 10MUM forskolin abolished sex differences in cAMP levels, as well as
      differences in Ca(2+) transients, sparks, and gain. To determine if the breakdown
      of cAMP differed between the sexes, phosphodiesterase (PDE) mRNA levels were
      measured. PDE3 expression was similar in males and females, but PDE4B expression
      was higher in female ventricles. The inhibition of cAMP breakdown by PDE4 (10MUM
      rolipram) abolished differences in Ca(2+) transients and gain. These findings
      suggest that female myocytes have lower levels of basal cAMP due, in part, to
      higher expression of PDE4B. Lower cAMP levels in females may attenuate PKA
      phosphorylation of Ca(2+) handling proteins in females, and may limit positive
      inotropic responses to stimulation of the cAMP/PKA pathway in female hearts. 

PMID- 25066698
TI  - Test-retest consistency of Virtual Week: A task to investigate prospective
      memory.
AB  - The present study reports test-retest consistency of Virtual Week, a well-known
      measure of prospective memory (PM) performance. PM is the memory associated with
      carrying out actions at a specific moment in the future. Patients with
      neurological disorders as well as healthy older adults often report PM
      dysfunctions that affect their everyday living. In Experiment 1, 19 younger and
      20 older adults undertook the standard version of Virtual Week (version A). Older
      adults showed lower performance compared to younger participants. However, the
      discrepancy between groups was eliminated at retest. Experiment 2 was conducted
      to investigate if remembering of PM content determined the improvement observed
      in older adults at retest in Experiment 1. To this end we created a parallel
      version (version B) in which we varied the content of the PM actions. Fifty older
      adults were assigned to one of the two experimental conditions: Version A at test
      and version B at retest or vice versa (25 participants in each condition).
      Results showed no group differences in PM performance between version A and
      version B; moreover, no effect of test-retest was found. The study confirmed that
      Virtual Week is a reliable measure of PM performance and also provided a new
      parallel version that can be useful in clinical setting. 

PMID- 25066699
TI  - Effect of food matrix microstructure on stomach emptying rate and apparent ileal
      fatty acid digestibility of almond lipids.
AB  - Almond lipids can be consumed in different forms such as nuts, oil-in-water
      emulsions or oil. The stomach emptying rate (SER) of almond lipids (0.2 g of fat
      per 2 mL of almond lipid suspension) as a function of the food matrix was studied
      using magnetic resonance spectroscopy based on the stomach emptying of a marker
      (AlCl3-6H2O) in the growing rat. Chyme and digesta samples were collected
      following serial gavaging (0.2 g of fat per 2 mL of almond lipid suspension) to
      study microstructural changes and determine the apparent ileal digestibility of
      almond fatty acids as a function of the native food matrix. The T(1/2) for the
      stomach emptying of crushed whole almonds and almond cream (194 +/- 17 min and
      185 +/- 19 min, respectively) were not different (P > 0.05) from that of a
      gastric-stable Tween-oil emulsion (197 +/- 19 min). The T(1/2) values for a
      sodium caseinate (NaCas)-oil emulsion (145 +/- 11 min) and a gastric-unstable
      Span-oil emulsion (135 +/- 7 min) were different (P < 0.05) from those for
      crushed whole almonds, almond cream and Tween-oil emulsion, while almond milk and
      oil emptied at an intermediate rate (157 +/- 9 min and 172 +/- 11 min,
      respectively). Extensively coalesced emulsions under gastric conditions (almond
      oil, almond cream and Span-oil) had lower (P < 0.05) overall apparent ileal fatty
      acid digestibility (85.8%, 75.8% and 74.3%, respectively) than crushed whole
      almonds, almond milk, NaCas-oil and Tween-oil emulsions (91.0%, 92.2%, 92.1% and
      88.7%, respectively). The original food matrix and structural changes occurring
      within the gastrointestinal tract had an impact on SER and ileal fatty acid
      digestibility of the almond preparations. 

PMID- 25066700
TI  - A study on early-onset neonatal group B streptococcal infection, Bulgaria, 2007
      2011.
AB  - This study examines neonatal group B streptococcal (GBS) colonization and its
      relation to early-onset GBS disease (EOGBSD), based upon the experience of
      leading obstetrics and gynecology centers in Bulgaria. The objectives of the
      study were to update neonatal colonization rates and to assess relationships
      between clinically differentiated cases (culture-proven GBS newborns) and risk
      factors inherent to the infant and mother, using a computerized file. The
      neonatal GBS colonization rate ranged from 5.48 to 12.19 per 1000 live births.
      Maternal-fetal infection (MFI, a provisional clinical diagnosis in culture-proven
      colonized infants with initial signs of infection that is usually overcome with
      antibiotic treatment) and/or intrapartum asphyxia (IA) have been demonstrated as
      the most frequent clinical manifestations, with significant correlations for the
      primary diagnosis, but not affirmative for the final diagnosis at discharge,
      resulting from adequate treatment of neonates. MFI and IA were significantly
      related to prematurity, and reciprocally, prematurity was associated with the
      risk of MFI, indirectly suggesting that preterm birth or PPROM (preterm premature
      rupture of membranes, an obstetric indication associated with early labor and
      delivery, one of the major causes of preterm birth) is a substantial risk factor
      for EOGBSD. The regression analysis indicated that in the case of a newborn with
      MFI, a birth weight 593.58 g lower than the birth weight of an infant without
      this diagnosis might be expected. Testing the inverse relationship, i.e., the way
      birth weight influences a certain diagnosis (logistic regression) established the
      presence of a relationship between birth weight categories (degree of
      prematurity) and the diagnosis of MFI. The proportions and odds ratios, converted
      into probabilities that a baby would develop MFI, indicate the particularly high
      risk for newborns with extremely low and very low birth weight: extremely low
      birth weight (<=1000 g), the probability of developing a MFI is 66%; very low
      birth weight (1001-1500 g), 81%; low birth weight (the birth weight category
      including premature and small for gestational age term infants: 1501-2500 g),
      40%; normal birth weight (term infants) (>2500 g), 32%. In conclusion, the need
      to introduce separate categories for early- and late-onset GBS disease in the
      registration nomenclature of neonatal infectious diseases is highlighted by these
      results. Drawing up intrapartum antibiotic prophylaxis (IAP) guidelines is also
      strongly recommended.

PMID- 25066701
TI  - [Pain in neonatology. Non-pharmacological treatment].
AB  - Diagnostic and therapeutic skin-breaking procedures have become ubiquitous in
      current medical practice and neonatology does not constitute an exception. One of
      the main sources of neonatal pain is procedure-induced pain. It has recently
      become clear that pain prevention must be a health care priority. Non
      pharmacological approaches constitute a first option for the analgesia of common
      procedures performed in neonatology. This article reviews the non-pharmacological
      treatments most frequently used in this context: swaddling, tucking, containment,
      sweet solutions, non-nutritive sucking (NNS), breastfeeding analgesia, breast
      milk and music. In practice, the dose of 1 to 2mL of 24% or 30% sucrose solution
      or 30% glucose solution immediately followed by NNS can be given for minor
      painful procedures in term neonates or those weighing more than 2500g. In the
      preterm, 0.3mL of a sweet solution (sucrose or glucose) can be given for infants
      weighing less than 1500g and 0.5mL for those weighing between 1500 and 2500g. The
      synergistic effect of sweet solutions and NNS has been clearly shown and thus
      their association is largely justified in practice. For breast-fed term neonates,
      breastfeeding can be given to sooth procedure-induced pain. All these non
      pharmacological options can be effective to relieve pain from minor or moderate
      procedures. However, when more painful procedures are performed, stronger
      analgesics must be used. 

PMID- 25066702
TI  - White matter integrity in alcohol-naive youth with a family history of alcohol
      use disorders.
AB  - BACKGROUND: Understanding pre-existing neural vulnerabilities found in youth who
      are family history positive (FHP) for alcohol use disorders could help inform
      preventative interventions created to delay initiation age and escalation of
      heavy drinking. The goal of this study was to compare indices of white matter
      integrity using diffusion tensor imaging (DTI) between FHP and family history
      negative (FHN) youth using a sample of 94 alcohol-naive adolescents and to
      examine if differences were associated with global and domain-specific cognitive
      functioning. METHOD: Participants were 48 FHP and 46 FHN demographically matched,
      healthy, substance-naive 12- to 14-year-olds (54% female) recruited from local
      middle schools. Participants completed a neuropsychological test battery and
      magnetic resonance imaging session, including DTI. RESULTS: FHP youth had higher
      fractional anisotropy and axial diffusivity, and lower radial and mean
      diffusivity, than FHN youth in 19 clusters spanning projection, association and
      interhemispheric white matter tracts. Findings were replicated after controlling
      for age, gender, socio-economic status, grade and pubertal development. Groups
      did not differ significantly on global or domain-specific neuropsychological test
      scores. CONCLUSIONS: FHP teens showed higher white matter integrity, but similar
      cognitive functioning, to FHN youth. More mature neural features could be related
      to more precocious behaviors, such as substance use initiation, in FHP youth.
      Future research exploring white matter maturation before and after substance use
      initiation will help elucidate the neurodevelopmental trajectories in youth at
      risk for substance use disorders, to inform preventive efforts and better
      understand the sequelae of adolescent alcohol and drug use.

PMID- 25066703
TI  - Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and
      thalamus as a function of mild depressive symptoms: a voxel-based morphometric
      analysis.
AB  - BACKGROUND: Studies investigating structural brain abnormalities in depression
      have typically employed a categorical rather than dimensional approach to
      depression [i.e., comparing subjects with Diagnostic and Statistical Manual of
      Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy
      controls]. The National Institute of Mental Health, through their Research Domain
      Criteria initiative, has encouraged a dimensional approach to the study of
      psychopathology as opposed to an over-reliance on categorical (e.g., DSM-based)
      diagnostic approaches. Moreover, subthreshold levels of depressive symptoms
      (i.e., severity levels below DSM criteria) have been found to be associated with
      a range of negative outcomes, yet have been relatively neglected in neuroimaging
      research. METHOD: To examine the extent to which depressive symptoms--even at
      subclinical levels--are linearly related to gray matter volume reductions in
      theoretically important brain regions, we employed whole-brain voxel-based
      morphometry in a sample of 54 participants. RESULTS: The severity of mild
      depressive symptoms, even in a subclinical population, was associated with
      reduced gray matter volume in the orbitofrontal cortex, anterior cingulate,
      thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A
      conjunction analysis revealed concordance across two separate measures of
      depression. CONCLUSIONS: Reduced gray matter volume in theoretically important
      brain regions can be observed even in a sample that does not meet DSM criteria
      for MDD, but who nevertheless report relatively elevated levels of depressive
      symptoms. Overall, these findings highlight the need for additional research
      using dimensional conceptual and analytic approaches, as well as further
      investigation of subclinical populations.

PMID- 25066704
TI  - Epidural abscess caused by Veillonella parvula: Case report and review of the
      literature.
AB  - Veillonella parvula, an anaerobic, Gram-negative coccus is part of the normal
      flora of the oral, gastrointestinal, respiratory, and genitourinary tracts in
      humans and animals. We herein present a case of epidural abscess caused by V.
      parvula in a 68-year-old man with sinus squamous cell carcinoma who presented
      with a 3-week history of low back pain. Blood and pus cultures were positive for
      Veillonella spp. After sequencing of the 16S ribosomal DNA, the pathogen was
      identified as V. parvula. Surgical debridement was performed following which the
      patient received intravenous administration of amoxicillin/clavulanate. To our
      knowledge, there are only seven reported cases of spinal infection caused by
      Veillonella spp. and these are reviewed here.

PMID- 25066705
TI  - Gas-forming Klebsiella pneumoniae liver abscess in a patient without diabetes.

PMID- 25066706
TI  - Empyema thoracis due to Nocardia otitidiscaviarum.

PMID- 25066707
TI  - Comorbidities of pediatric systemic lupus erythematosus: A 6-year nationwide
      population-based study.
AB  - OBJECTIVE: Systemic lupus erythematous (SLE) is a systemic and complex disease
      that can involve multiple organs. To clarify the risk of developing associated
      comorbidities after a diagnosis of SLE in children, we used the National Health
      Insurance Research Database (NHIRD) in Taiwan to investigate diseases experienced
      in these patients. This is the first nationwide population-based study of the
      comorbidities of pediatric SLE patients. METHODS: The study was based on data
      from the NHIRD in Taiwan. Children were enrolled who were below the age of 18
      years and whose disease corresponded to the International Classification of
      Disease, Ninth Revision Clinical Modification (ICD-9-CM) diagnostic code of 710.0
      (SLE). The comorbidities associated with SLE were defined by the ICD-9-CM codes
      of diseases that presented after the SLE diagnosis. We analyzed the common
      diseases in SLE patients and compared the frequency of these diseases between
      pediatric SLE patients and the non-SLE population. RESULTS: From January 1, 2003
      to December 31, 2008, we enrolled 904 SLE patients (774 females, 130 males).
      Infection (86.36%) was the most common comorbidity in pediatric SLE. Other
      comorbidities were musculoskeletal diseases (16.7%), cardiovascular diseases
      (16.37%), ocular diseases (10.73%), and renal diseases (6.75%). Children with SLE
      had a higher risk of heart failure, hypertension, osteoporosis, cataracts,
      glaucoma, dyslipidemia, seizures, encephalopathy, and malignant changes, compared
      to non-SLE populations. CONCLUSION: The population-based cohort demonstrated
      several systemic and/or chronic diseases in pediatric SLE patients in Taiwan.
      Children with SLE were more susceptible to these diseases, including malignancy,
      compared to the non-SLE population.

PMID- 25066708
TI  - Increased frequency of peripheral venipunctures raises the risk of central-line
      associated bloodstream infection in neonates with peripherally inserted central
      venous catheters.
AB  - BACKGROUND/PURPOSE: Central-line associated bloodstream infection (CLA-BSI),
      which is mostly caused by coagulase-negative staphylococcus, is an important
      morbidity in neonatal intensive care units. Our study is aimed to identify the
      risk factors of CLA-BSI in neonates with peripherally inserted central venous
      catheters (PICCs). METHODS: A retrospective cohort study of neonatal intensive
      care unit patients with a PICC insertion between January 1, 2011 and December 31,
      2012 was conducted. We performed univariate and multivariate analyses with a
      logistic regression model to investigate the risk factors and the association
      between increased frequency of peripheral venipunctures during PICC use and the
      risk of CLA-BSI while adjusting for other variables. RESULTS: There were 123
      neonates included in our study. Thirteen CLA-BSIs were recorded within the follow
      up period. The incidence of PICC-associated CLA-BSI was 4.99 per 1000 catheter
      days. There was no statistically significant association between the risk of CLA
      BSI and gestational age, birth weight, chronological age, or other comorbidities.
      However, the odds of CLS-BSI increased to 12 times if the patient received six or
      more venipunctures within the period without concurrent antibiotic use [odds
      ratio (OR), 11.94; p < 0.001]. The OR of CLA-BSIs increased by 16% per
      venipuncture during PICC use (OR, 1.14; p = 0.003). CONCLUSION: During PICC use,
      increased frequency of venipunctures, especially when there was no concurrent
      antibiotic use, substantially raises the risk of CLA-BSI. By decreasing
      unnecessary venipunctures during PICC use, PICC-associated CLA-BSI and further
      morbidities and mortalities can be prevented.

PMID- 25066709
TI  - Inorganic-organic hybrid nanoprobe for NIR-excited imaging of hydrogen sulfide in
      cell cultures and inflammation in a mouse model.
AB  - Hydrogen sulfide (H2S) is an important gaseous signaling agent mediated by many
      physiological processes and diseases. In order to explore its role in biological
      signaling, much effort has been focused on developing organic fluorescent probes
      to image H2S. However, these downconversion H2S probes are impractical for bio
      imaging beyond a certain depth because of the short tissue penetration of
      UV/visible light (as an excitation source). In most circumstance, these probes
      are also not suitable for long-term assay due to photo-bleaching. Herein, a new
      design to detect H2S based on the coumarin-hemicyanine (CHC1)-modified
      upconversion nanophosphors is reported. This inorganic-organic integrated
      nanoprobe is demonstrated to display a fast response time with a large
      ratiometric upconversion luminescence (UCL) enhancement, and extraordinary photo
      stability. CHC1-UCNPs not only can be used for ratiometric UCL monitoring of
      pseudo-enzymatic H2S production in living cells, but can also be used to identify
      the risk of endotoxic shock through ratiometric UCL imaging of tissue and
      measurement of endogenous H2S levels in plasma. The first ratiometric UCL H2S
      nanoprobe reported here may be further developed as the next-generation
      diagnostic tool for the detection of inflammatory-related diseases.

PMID- 25066710
TI  - Hierarchical Zn/Ni-MOF-2 nanosheet-assembled hollow nanocubes for multicomponent
      catalytic reactions.
AB  - Metal-organic frameworks (MOFs) are potentially useful molecular materials that
      can exhibit structure flexibilities induced by some external stimuli. Such
      structure transformations can furnish MOFs with improved properties. The shape
      controlled growth of MOFs combined with crystal-structure transformation is
      rarely achieved. Herein, we demonstrate the synthesis of hierarchical Zn/Ni-MOF-2
      nanosheet-assembled hollow nanocubes (NAHNs) by a facile surfactant-free
      solvothermal approach. The unique nanostructures undergo crystal-structure
      transformation from Zn/Ni-MOF-5 nanocubes to Zn/Ni-MOF-2 nanosheets, which is
      analogous to the dissolution and recrystallization of inorganic nanocrystals. The
      present synthetic strategy to fabricate isostructural MOFs with hierarchical,
      hollow, and bimetallic nanostructures is expected to expand the diversity and
      range of potential applications of MOFs. 

PMID- 25066712
TI  - Direct analysis of anabolic steroids in urine using Leidenfrost phenomenon
      assisted thermal desorption-dielectric barrier discharge ionization mass
      spectrometry.
AB  - Rapid detection of trace level anabolic steroids in urine is highly desirable to
      monitor the consumption of performance enhancing anabolic steroids by athletes.
      The present article describes a novel strategy for identifying the trace anabolic
      steroids in urine using Leidenfrost phenomenon assisted thermal desorption (LPTD)
      coupled to dielectric barrier discharge (DBD) ionization mass spectrometry. Using
      this method the steroid molecules are enriched within a liquid droplet during the
      thermal desorption process and desorbed all-together at the last moment of
      droplet evaporation in a short time domain. The desorbed molecules were ionized
      using a dielectric barrier discharge ion-source in front of the mass spectrometer
      inlet at open atmosphere. This process facilitates the sensitivity enhancement
      with several orders of magnitude compared to the thermal desorption at a lower
      temperature. The limits of detection (LODs) of various steroid molecules were
      found to be in the range of 0.05-0.1 ng mL(-1) for standard solutions and around
      two orders of magnitude higher for synthetic urine samples. The detection limits
      of urinary anabolic steroids could be lowered by using a simple and rapid
      dichloromethane extraction technique. The analytical figures of merit of this
      technique were evaluated at open atmosphere using suitable internal standards.
      The technique is simple and rapid for high sensitivity and high throughput
      screening of anabolic steroids in urine.

PMID- 25066713
TI  - Elemental ratios for characterization of quantum-dots populations in complex
      mixtures by asymmetrical flow field-flow fractionation on-line coupled to
      fluorescence and inductively coupled plasma mass spectrometry.
AB  - Separation and identification of nanoparticles of different composition, with
      similar particle diameter, coexisting in heterogeneous suspensions of polymer
      coated CdSe/ZnS quantum dots (QDs) have been thoroughly assessed by asymmetric
      flow field-flow fractionation (AF4) coupled on-line to fluorescence and
      inductively coupled plasma mass spectrometry (ICPMS) detectors. Chemical
      characterization of any previously on-line separated nanosized species was
      achieved by the measurement of the elemental molar ratios of every element
      involved in the synthesis of the QDs, using inorganic standards and external
      calibration by flow injection analysis (FIA). Such elemental molar ratios,
      strongly limited so far to pure single nanoparticles suspensions, have been
      achieved with adequate accuracy by coupling for the first time an ICP-QQQ
      instrument to an AF4 system. This hyphenation turned out to be instrumental to
      assess the chemical composition of the different populations of nanoparticles
      coexisting in the relatively complex mixtures, due to its capabilities to detect
      the hardly detectable elements involved in the synthesis. Interestingly such
      information, complementary to that obtained by fluorescence, was very valuable to
      detect and identify unexpected nanosized species, present at significant level,
      produced during QDs synthesis and hardly detectable by standard approaches. 

PMID- 25066711
TI  - Global and gene-specific DNA methylation pattern discriminates cholecystitis from
      gallbladder cancer patients in Chile.
AB  - AIM: The aim of the study was to evaluate the use of global and gene-specific DNA
      methylation changes as potential biomarkers for gallbladder cancer (GBC) in a
      cohort from Chile. MATERIAL & METHODS: DNA methylation was analyzed through an
      ELISA-based technique and quantitative methylation-specific PCR. RESULTS: Global
      DNA Methylation Index (p = 0.02) and promoter methylation of SSBP2 (p = 0.01) and
      ESR1 (p = 0.05) were significantly different in GBC when compared with
      cholecystitis. Receiver curve operator analysis revealed promoter methylation of
      APC, CDKN2A, ESR1, PGP9.5 and SSBP2, together with the Global DNA Methylation
      Index, had 71% sensitivity, 95% specificity, a 0.97 area under the curve and a
      positive predictive value of 90%. CONCLUSION: Global and gene-specific DNA
      methylation may be useful biomarkers for GBC clinical assessment.

PMID- 25066715
TI  - Reusable and robust high sensitive non-enzymatic glucose sensor based on Ni(OH)2
      nanoparticles.
AB  - Nickel hydroxide nanoparticles were successfully electrodeposited on graphite
      electrode (Gr/NiONP) and employed as a robust non-enzymatic glucose sensor. The
      results of cyclic voltammetry (CV) and chronoamperometry demonstrated that the
      Gr/NiONP electrode displayed high electrocatalytic activity toward glucose. The
      oxidation current is directly related to the glucose concentration from 1 MUM to
      15 mM. Besides, the glucose sensor displayed high sensitivity (2400 MUA mM(-1)
      cm(-2)) with a detection limit of 0.53 MUM (S/N=3) in basic solution. Moreover,
      the sensor showed excellent selectivity, reproducibility and stability
      properties. The relative standard deviation is 1.2% for 10 successive
      measurements in 16 MUM glucose. Interestingly, the signal for glucose was
      maintained at 95% of its initial value even after 6 months of storage under
      ambient conditions. Gr/NiONP electrode has also been tested to detect glucose in
      human serum with satisfactory results.

PMID- 25066714
TI  - Independent components analysis coupled with 3D-front-face fluorescence
      spectroscopy to study the interaction between plastic food packaging and olive
      oil.
AB  - Olive oil is one of the most valued sources of fats in the Mediterranean diet.
      Its storage was generally done using glass or metallic packaging materials.
      Nowadays, plastic packaging has gained worldwide spread for the storage of olive
      oil. However, plastics are not inert and interaction phenomena may occur between
      packaging materials and olive oil. In this study, extra virgin olive oil samples
      were submitted to accelerated interaction conditions, in contact with
      polypropylene (PP) and polylactide (PLA) plastic packaging materials. 3D-front
      face fluorescence spectroscopy, being a simple, fast and non destructive
      analytical technique, was used to study this interaction. Independent components
      analysis (ICA) was used to analyze raw 3D-front-face fluorescence spectra of
      olive oil. ICA was able to highlight a probable effect of a migration of
      substances with antioxidant activity. The signals extracted by ICA corresponded
      to natural olive oil fluorophores (tocopherols and polyphenols) as well as newly
      formed ones which were tentatively identified as fluorescent oxidation products.
      Based on the extracted fluorescent signals, olive oil in contact with plastics
      had slower aging rates in comparison with reference oils. Peroxide and free
      acidity values validated the results obtained by ICA, related to olive oil
      oxidation rates. Sorbed olive oil in plastic was also quantified given that this
      sorption could induce a swelling of the polymer thus promoting migration. 

PMID- 25066716
TI  - Selectivity assessment of an arsenic sequential extraction procedure for
      evaluating mobility in mine wastes.
AB  - An optimized sequential extraction (SE) scheme for mine waste materials has been
      developed and tested for As partitioning over a range of pure As-bearing mineral
      phases, their model mixtures, and natural mine waste materials. This optimized SE
      procedure employs five extraction steps: (1) nitrogen-purged deionized water,
      10h; (2) 0.01 M NH4H2PO4, 16 h; (3) 0.2M NH4-oxalate in the dark, pH3, 2 h; (4)
      0.2 M NH4-oxalate, pH3/80 degrees C, 4 h; (5) KClO3/HCl/HNO3 digestion.
      Selectivity and specificity tests on natural mine wastes and major pure As
      bearing mineral phases showed that these As fractions appear to be primarily
      associated with: (1) readily soluble; (2) adsorbed; (3) amorphous and poorly
      crystalline arsenates, oxides and hydroxosulfates of Fe; (4) well-crystalline
      arsenates, oxides, and hydroxosulfates of Fe; as well as (5) sulfides and
      arsenides. The specificity and selectivity of extractants, and the
      reproducibility of the optimized SE procedure were further verified by artificial
      model mineral mixtures and different natural mine waste materials. Partitioning
      data for extraction steps 3, 4, and 5 showed good agreement with those calculated
      in the model mineral mixtures (<15% difference), as well as that expected in
      different natural mine waste materials. The sum of the As recovered in the
      different extractant pools was not significantly different (89-112%) than the
      results for acid digestion. This suggests that the optimized SE scheme can
      reliably be employed for As partitioning in mine waste materials.

PMID- 25066717
TI  - Untargeted fatty acid profiles based on the selected ion monitoring mode.
AB  - Fatty acids are potential biomarkers of some diseases and also key markers and
      quality parameters of different dietary fats and related products. Thus,
      untargeted fatty acid profiles are important in the study of dietary fat quality
      and fat-related diseases, as well as in other fields such as bioenergy. In
      addition, accurate identification of unknown components is a technological
      breakthrough for the selected ion monitoring (SIM) mode for untargeted profiles.
      In this study, we developed untargeted fatty acid profiles based on SIM. We also
      investigated mass spectral characteristics and equivalent chain lengths (ECL) to
      eliminate the influence of non-FAMEs for identifying fatty acids in samples. As
      an application example, fatty acid profiles were used to classify three edible
      vegetable oils. The results indicated that SIM-based untargeted fatty acid
      profiles could yield accurate qualitative and quantitative results for more fatty
      acids and benefit related studies of metabolite profiles. 

PMID- 25066718
TI  - Novel lanthanide pH fluorescent probes based on multiple emissions and its
      visible-light-sensitized feature.
AB  - A new type of Eu(III) ofloxacin complex as the fluorescent pH indicator has been
      presented. Compared to pure ligand, the complex offers more distinguished color
      changes (green-red-blue) derived from both lanthanide line emissions and the
      secondary ionization steps of ofloxacin. During the concentration dependence
      experiments, the photoluminescence studies on the complex showed that the
      excitation of this pH probe can occur at a very long wavelength which extends to
      visible range (Ex=427 nm). Furthermore, the functional complex was successfully
      incorporated into soft networks and two novel luminescent hydrogels (rod and
      film) were fabricated. The soft materials also exhibited specific responses
      towards the pH variation. Finally, the onion cell-stain experiments were carried
      out to further confirm the validity of pH dependence and the results support the
      idea that the material will be suitable for monitoring biological samples in the
      future.

PMID- 25066719
TI  - An electrochemical sensor prepared by sonochemical one-pot synthesis of multi
      walled carbon nanotube-supported cobalt nanoparticles for the simultaneous
      determination of paracetamol and dopamine.
AB  - Multi-walled carbon nanotubes (MWCNTs) functionalized by cobalt nanoparticles
      were obtained using a single step chemical deposition method in an ultrasonic
      bath. The composite material was characterized using scanning electron microscopy
      (SEM) and energy dispersive X-ray analysis (EDX). The electroactivity of the
      cobalt-functionalized MWCNTs was assessed in respect to the electrooxidation of
      paracetamol (PAR) and dopamine (DA). It was found that the carbon nanotube
      supported cobalt nanoparticles have significantly higher catalytic properties.
      The proposed electrode has been applied for the simultaneous determination of PAR
      and DA. The modified electrode could resolve the overlapped voltammetric waves of
      PAR and DA into two well-defined voltammetric peaks with peak to peak separation
      of about 203 mV. On the other hand, the presence of potential drug interfering
      compounds AA and UA did not affect the voltammetric responses of PAR and DA. The
      current of oxidation peaks showed a linear dependent on the concentrations of PAR
      and DA in the range of 5.2*10(-9)-4.5*10(-7) M (R(2)=0.9987) and 5.0*10(-8)
      3.0*10(-6) M (R(2)=0.9999), respectively. The detection limits of 1.0*10(-9) M
      and 1.5*10(-8) M were obtained for PAR and DA, respectively. The proposed
      electrode showed good stability (peak current change: 4.9% with and RSD of 2.6%
      for PAR; 5.5% with and RSD of 3.0% for DA over 3 weeks), reproducibility (RSD
      2.3% for PAR and RSD 1.5% for DA), repeatability (RSD 2.25% for PAR and RSD 2.50%
      for DA) and high recovery (99.7% with an RSD of 1.3% for PAR; 100.8% with an RSD
      of 1.8% for DA). The proposed method was successfully applied to the
      determination of PAR and DA in pharmaceuticals.

PMID- 25066720
TI  - A streptavidin functionalized graphene oxide/Au nanoparticles composite for the
      construction of sensitive chemiluminescent immunosensor.
AB  - In this work, a novel streptavidin functionalized graphene oxide/Au nanoparticles
      (streptavidin/GO/AuNPs) composite is prepared and for the first time used to
      construct sensitive chemiluminescent immunosensor for the detection of tumor
      marker. The streptavidin/GO/AuNPs composite and the immunosensor are
      characterized using scanning electron microscopy, static water contact angle
      measurement and electrochemical impedance spectroscopy. The biofunctionalized
      composite has large reactive surface area and excellent biocompatibility, thus
      the capture antibody can be efficiently immobilized on its surface based on the
      highly selective recognition of streptavidin to biotinylated antibody. Using
      alpha-fetoprotein (AFP) as a model, the proposed chemiluminescent immunosensor
      shows a wide linear range from 0.001 to 0.1 ng mL(-1) with an extremely low
      detection limit down to 0.61 pg mL(-1). The resulting AFP immunosensor shows high
      detection sensitivity, fast assay speed, acceptable detection and fabrication
      reproducibility, good specificity and stability. The assay results of serum
      samples with the proposed method are in an acceptable agreement with the
      reference values. This work provides a promising biofunctionalized nanostructure
      for sensitive biosensing applications.

PMID- 25066721
TI  - Single-fluorophore-based fluorescent probes enable dual-channel detection of Ag+
      and Hg2+ with high selectivity and sensitivity.
AB  - A new type of fluorescent probe capable of detecting Ag(+) and Hg(2+) in two
      independent channels was developed in the present work. Specifically, in CH3CN
      MOPS mixed solvents with CH3CN/MOPS ratio (v/v) of 15/85, this type of probe
      fluoresced weakly, and the addition of Ag(+) remarkably induced fluorescence
      enhancement of the probe. In CH3CN-MOPS mixed solvents with the percentage of
      CH3CN increased up to 65%, the probe was highly fluorescent and addition of
      Hg(2+) dramatically induced the fluorescence quenching. Thus, using such single
      fluorophore-based probe and tuning the polarity of the mixed solvent, Ag(+), and
      Hg(2+) can be detected in independent channels with high selectivity and
      sensitivity. As a result, the mutual interference usually encountered in most
      cases of Ag(+) and Hg(2+) sensing owing to the similar fluorescence response that
      these two ions induced, can be effectively circumvented by using the probes
      developed herein. 

PMID- 25066722
TI  - Rapid colorimetric sensing of tetracycline antibiotics with in situ growth of
      gold nanoparticles.
AB  - A colorimetric assay utilizing the formation of gold nanoparticles was developed
      to detect tetracycline antibiotics in fluidic samples. Tetracycline antibiotics
      showed the capability of directly reducing aurate salts into atomic gold which
      form gold nanoparticles spontaneously under proper conditions. The resulted gold
      nanoparticles showed characteristic plasmon absorbance at 526 nm, which can be
      visualized by naked eyes or with a spectrophotometer. UV-vis absorbance of the
      resulted gold nanoparticles is correlated directly with the concentrations of
      tetracycline antibiotics in the solution, allowing for quantitative colorimetric
      detection of tetracycline antibiotics. Reaction conditions, such as pH,
      temperature, reaction time, and ionic strength were optimized. Sensitivity of the
      colorimetric assay can be enhanced by the addition of gold nanoparticle seeds, a
      LOD as low as 20 ng mL(-1) can be achieved with the help of seed particles. The
      colorimetric assay showed minimum interference from ethanol, methanol, urea,
      glucose, and other antibiotics such as sulfonamides, amino glycosides etc.
      Validity of the method was also evaluated on urine samples spiked with
      tetracycline antibiotics. The method provides a broad spectrum detection method
      for rapid and sensitive detection of reductive substances such as tetracycline
      antibiotics in liquid and biological samples.

PMID- 25066723
TI  - Highly sensitive multianalyte immunochromatographic test strip for rapid
      chemiluminescent detection of ractopamine and salbutamol.
AB  - A novel immunochromatographic assay (ICA) was proposed for rapid and multiple
      assay of beta2-agonists, by utilizing ractopamine (RAC) and salbutamol (SAL) as
      the models. Owing to the introduction of chemiluminescent (CL) approach, the
      proposed protocol shows much higher sensitivity. In this work, the described ICA
      was based on a competitive format, and horseradish peroxidase-tagged antibodies
      were used as highly sensitive CL probes. Quantitative analysis of beta2-agonists
      was achieved by recording the CL signals of the probes captured on the two test
      zones of the nitrocellulose membrane. Under the optimum conditions, RAC and SAL
      could be detected within the linear ranges of 0.50-40 and 0.10-50 ng mL(-1), with
      the detection limits of 0.20 and 0.040 ng mL(-1) (S/N=3), respectively. The whole
      process for multianalyte immunoassay of RAC and SAL can be completed within 20
      min. Furthermore, the test strip was validated with spiked swine urine samples
      and the results showed that this method was reliable in measuring beta2-agonists
      in swine urine. This CL-based multianalyte test strip shows a series of
      advantages such as high sensitivity, ideal selectivity, simple manipulation, high
      assay efficiency and low cost. Thus, it opens up new pathway for rapid screening
      and field analysis, and shows a promising prospect in food safety.

PMID- 25066724
TI  - [Review of the current value of ultrasonography in the characterization of
      thyroid nodules].
AB  - The widespread use of medical imaging to study diseases of the neck reveals the
      prevalence of thyroid nodules can be as high as 67%. This is an important problem
      for the healthcare system because after analyzing the characteristics of the
      nodules a decision must be made regarding whether to perform fine-needle
      aspiration cytology to determine whether the lesion is malignant. In this
      article, we review the techniques for ultrasonographic study and fine-needle
      aspiration. We discuss the different guidelines for characterizing thyroid
      nodules and the criteria that help determine which patients need fine-needle
      aspiration for diagnosis and when an invasive procedure is unnecessary and can be
      avoided. Close collaboration with the different specialists involved in the
      management of thyroid nodules helps optimize resources and diagnostic
      performance. 

PMID- 25066725
TI  - [Optical colonoscopy and virtual colonoscopy: the current role of each
      technique].
AB  - The importance of optical or conventional colonoscopy in diagnosing colon disease
      is undisputed. In this context, optical colonoscopy is the gold standard against
      which other techniques must be validated. Apart from enabling direct inspection
      of the colonic mucosa, optical colonoscopy enables biopsies and techniques to
      treat and prevent colorectal cancer. Virtual colonoscopy or CT colonography has
      been validated in multicenter studies; virtual colonoscopy is as sensitive as
      optical colonoscopy for the detection of polyps and colon cancer. It is currently
      the only valid alternative to optical colonoscopy. Its role in patients with
      medium or high risk of colon cancer is in the process of being defined as
      multidisciplinary teams gain experience. This article aims to discuss the
      usefulness of virtual colonoscopy in different clinical situations, emphasizing
      the situations in which there is enough scientific evidence, and to discuss the
      controversies surrounding its possible use for population-based screening. 

PMID- 25066726
TI  - Patterns of DNA damage response in intracranial germ cell tumors versus
      glioblastomas reflect cell of origin rather than brain environment: implications
      for the anti-tumor barrier concept and treatment.
AB  - The DNA damage response (DDR) machinery becomes commonly activated in response to
      oncogenes and during early stages of development of solid malignancies, with an
      exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes
      cell death or senescence but this anti-tumor barrier can be breached by defects
      in DDR factors, such as the ATM-Chk2-p53 pathway, thereby allowing tumor
      progression. The DDR barrier is strongly activated in brain tumors, particularly
      gliomas, due to oxidative damage and replication stress. Here, we took advantage
      of rare human primary intracranial germ cell tumors (PIGCTs), to address the
      roles of cell-intrinsic factors including cell of origin, versus local tissue
      environment, in the constitutive DDR activation in vivo. Immunohistochemical
      analysis of 7 biomarkers on a series of 21 PIGCTs (germinomas and other
      subtypes), 20 normal brain specimens and 20 glioblastomas, revealed the
      following: i) The overall DDR signaling (gammaH2AX) and activation of the ATM
      Chk2-p53 pathway were very low among the PIGCTs, reminiscent of TGCTs, and
      contrasting sharply with strong DDR activation in glioblastomas; ii) Except for
      one case of embryonal carcinoma, there were no clear aberrations in the ATM-Chk2
      p53 pathway components among the PIGCT cohort; iii) Subsets of PIGCTs showed
      unusual cytosolic localization of Chk2 and/or ATM. Collectively, these results
      show that PIGCTs mimic the DDR activation patterns of their gonadal germ cell
      tumor counterparts, rather than the brain tumors with which they share the tissue
      environment. Hence cell-intrinsic factors and cell of origin dictate the extent
      of DDR barrier activation and also the ensuing pressure to select for DDR
      defects. Our data provide conceptually important insights into the role of DNA
      damage checkpoints in intracranial tumorigenesis, with implications for the
      differential biological responses of diverse tumor types to endogenous stress as
      well as to genotoxic treatments such as ionizing radiation or chemotherapy. 

PMID- 25066728
TI  - Mimicking caloric restriction: what about macronutrient manipulation? A response
      to Meynet and Ricci.
AB  - As ongoing research continues to reveal the links between metabolism, cancer, and
      aging it is good to see non-toxic interventions such as caloric restriction (CR)
      coming into focus. Recently, Meynet and Ricci provided a timely review
      summarizing the current state of research on the possible role of CR in cancer
      treatment. In discussing ways to implement clinically the beneficial effects of
      CR without a need for overall reduced food intake these authors focused on CR
      mimicking drugs that have several limitations. I propose carbohydrate restriction
      as probably the best way to mimic CR in humans without the need to restrict
      energy intake. 

PMID- 25066729
TI  - Neuroendocrinology of the hair follicle: principles and clinical perspectives.
AB  - The human hair follicle (HF) is an exquisitely hormone-sensitive mini-organ that
      undergoes cyclical remodeling. It is also a source and target of numerous
      neurohormones, neuropeptides, and neurotransmitters that regulate HF growth,
      pigmentation, remodeling, immune status, stem cell biology, and energy
      metabolism. Indeed, organ-cultured human scalp HFs can be utilized to identify
      'novel' clinically relevant functions of major neuromediators. This is
      pertinently illustrated by the discoveries of: (i) thyrotropin-releasing hormone
      (TRH) as a hair growth and pigmentation stimulator; (ii) TRH and thyrotropin
      (TSH) as potent promoters of mitochondrial activity and regulators of keratin
      expression; and (iii) prolactin as an epithelial stem cell modulator. Thus, HF
      neuroendocrinology affords insights well beyond hair growth and
      dermatoendocrinology, uncovering new translationally relevant neuroendocrinology
      principles and novel therapeutic targets. 

PMID- 25066727
TI  - GABAergic disinhibition and impaired KCC2 cotransporter activity underlie tumor
      associated epilepsy.
AB  - Seizures frequently accompany gliomas and often escalate to peritumoral epilepsy.
      Previous work revealed the importance of tumor-derived excitatory glutamate (Glu)
      release mediated by the cystine-glutamate transporter (SXC) in epileptogenesis.
      We now show a novel contribution of GABAergic disinhibition to disease
      pathophysiology. In a validated mouse glioma model, we found that peritumoral
      parvalbumin-positive GABAergic inhibitory interneurons are significantly reduced,
      corresponding with deficits in spontaneous and evoked inhibitory
      neurotransmission. Most remaining peritumoral neurons exhibit elevated
      intracellular Cl(-) concentration ([Cl(-) ]i ) and consequently depolarizing,
      excitatory gamma-aminobutyric acid (GABA) responses. In these neurons, the
      plasmalemmal expression of KCC2, which establishes the low [Cl(-) ]i required for
      GABAA R-mediated inhibition, is significantly decreased. Interestingly,
      reductions in inhibition are independent of Glu release, but the presence of both
      decreased inhibition and decreased SXC expression is required for
      epileptogenesis. We suggest GABAergic disinhibition renders peritumoral neuronal
      networks hyper-excitable and susceptible to seizures triggered by excitatory
      stimuli, and propose KCC2 as a therapeutic target.

PMID- 25066730
TI  - Concerns regarding the financial aspects of kidney transplantation: perspectives
      of pre-transplant patients and their family members.
AB  - BACKGROUND: African American and non-African American pre-transplant patients'
      and their families' concerns about the financial costs of kidney transplantation
      have not been well studied. METHODS: We conducted structured group interviews
      among pre-transplant patients (seven African American, five non-African American)
      and their family members (six African American, five non-African American) to
      identify their concerns about transplant health insurance coverage, out-of-pocket
      expenses, and living donor expenses. We reviewed transcribed group audio
      recordings and identified common discussion themes. RESULTS: African American and
      non-African American patients and family members expressed uncertainty about
      which transplant-related costs were covered by health insurance and wanted
      information about how to choose insurance policies accordingly. Patients were
      particularly concerned about the impact of pre-existing illness on securing
      optimal health insurance, while family members wanted information about non
      insurance-based financial resources. Both patients and family members expressed
      concern about paying for immunosuppressant medications and about gradual loss of
      insurance benefits after transplantation. Both patients and family members also
      expressed concern about potential financial hardships for living donors.
      CONCLUSION: African American and non-African American pre-transplant patients and
      families expressed a broad range of concerns about transplant health insurance
      policies, out-of-pocket expenses, non-insurance-based financial resources, and
      resources to address donors' financial burden. Efforts to improve education and
      develop more comprehensive transplant insurance policies are needed to facilitate
      informed decision-making for potential transplant recipients and donors.

PMID- 25066732
TI  - A new workflow for whole-genome sequencing of single human cells.
AB  - Unbiased amplification of the whole-genome amplification (WGA) of single cells is
      crucial to study cancer evolution and genetic heterogeneity, but is challenging
      due to the high complexity of the human genome. Here, we present a new workflow
      combining an efficient adapter-linker PCR-based WGA method with second-generation
      sequencing. This approach allows comparison of single cells at base pair
      resolution. Amplification recovered up to 74% of the human genome. Copy-number
      variants and loss of heterozygosity detected in single cell genomes showed
      concordance of up to 99% to pooled genomic DNA. Allele frequencies of mutations
      could be determined accurately due to an allele dropout rate of only 2%, clearly
      demonstrating the low bias of our PCR-based WGA approach. Sequencing with paired
      end reads allowed genome-wide analysis of structural variants. By direct
      comparison to other WGA methods, we further endorse its suitability to analyze
      genetic heterogeneity. 

PMID- 25066731
TI  - Receptor-interacting protein 140 attenuates endoplasmic reticulum stress in
      neurons and protects against cell death.
AB  - Inositol 1, 4, 5-trisphosphate receptor (IP3R)-mediated Ca(2+) release from the
      endoplasmic reticulum (ER) triggers many physiological responses in neurons, and
      when uncontrolled can cause ER stress that contributes to neurological disease.
      Here we show that the unfolded protein response (UPR) in neurons induces rapid
      translocation of nuclear receptor-interacting protein 140 (RIP140) to the
      cytoplasm. In the cytoplasm, RIP140 localizes to the ER by binding to the IP3R.
      The carboxyl-terminal RD4 domain of RIP140 interacts with the carboxyl-terminal
      gate-keeping domain of the IP3R. This molecular interaction disrupts the IP3R's
      'head-tail' interaction, thereby suppressing channel opening and attenuating IP3R
      mediated Ca(2+) release. This contributes to a rapid suppression of the ER stress
      response and provides protection from apoptosis in both hippocampal neurons in
      vitro and in an animal model of ER stress. Thus, RIP140 translocation to the
      cytoplasm is an early response to ER stress and provides protection against
      neuronal death. 

PMID- 25066733
TI  - Incorporation and washout of n-3 PUFA after high dose intravenous and oral
      supplementation in healthy volunteers.
AB  - BACKGROUND & AIMS: Although the physiological effects of n-3 polyunsaturated
      fatty acids (n-3PUFA) are generally thought to require several weeks of exposure
      to allow their incorporation into plasma membranes, intravenous (IV) n-3PUFA
      attenuate the cardiovascular and neuroendocrine response to stress within 3 h.
      Whether oral n-3 PUFA exert similar early effects remains unknown. OBJECTIVE: To
      assess whether acute IV or short term oral n-3PUFA administration reproduces the
      metabolic effects of long term oral supplements during exercise, and how it
      relates to their incorporation into platelets and red blood cells (RBC)
      membranes. DESIGN: Prospective single center open label study in 8 healthy
      subjects receiving a 3-h infusion of 0.6 g/kg body weight n-3PUFA emulsion,
      followed one week later by an oral administration of 0.6 g/kg over 3 consecutive
      days. Maximal power output (cycling exercise), maximal heart rate (HR), blood
      lactate at exhaustion, and platelet function were measured at baseline and after
      IV or 3-day oral supplementation; platelet and RBC membrane composition were
      assessed until 15 days after n-3PUFA administration. RESULTS: Both IV and oral n
      3PUFA significantly decreased maximal HR (-6% and -5%), maximal power output (
      10%) and peak blood lactate (-47% and -52%) Platelet function tests were
      unchanged. The EPA and DHA membrane contents of RBC and platelets increased
      significantly, but only to 1.7-1.9% of fatty acid content. CONCLUSION: The
      cardiovascular and metabolic effects of n-3 PUFA during exercise occur already
      within 1-3 days of exposure, and may be unrelated to changes in membranes
      composition. Effects occur within hours of administration and are unrelated to
      lipid membrane composition. Trial registered at clinicaltrials.gov as
      NCT00516178.

PMID- 25066734
TI  - Vaccination status, knowledge and awareness towards hepatitis B among students of
      health professions in Vientiane, Lao PDR.
AB  - Health care workers (HCW) are a population at high risk of hepatitis B virus
      (HBV) infection, especially in endemic countries such as Lao PDR. Effective
      vaccines are available since over 10 years, but many HCWs are not aware of the
      risk of infection and are still not immunized against hepatitis B. This study
      aimed to assess immunization coverage against hepatitis B among the students of
      the University of Health Sciences (UHS) of Lao PDR in 2013 and to look for the
      causes of non-vaccination. A cross-sectional survey was conducted by self
      administered questionnaire on a representative stratified sample of each academic
      year in each faculty. In total, 961 questionnaires were collected, Basic
      Sciences: 143, Medicine: 167, Pharmacy: 148, Dentistry: 139, Nursing Sciences:
      159, Medical Technology: 99, and Postgraduate Studies: 106. Respondents were
      predominantly female (59.1%), mean age 25.1+/-7.0 years, single (76.3%), from the
      provinces (68.0%), of the Lao Loum ethnic group (84.4%). Among them, 21% were
      fully vaccinated against hepatitis B and 9.5% partially. Immunization coverage
      rates were significantly higher among women (p=0.01), students aged over 25
      years, married or belonging to the post-graduate faculty (p<0.001). The most
      common reason (38.6%) given for non-vaccination was not knowing where to get
      vaccinated. Knowledge about hepatitis B, scored from 0 to 5, was poor (0-1) for
      86.5% of the students, but 77.5% were aware of the hepatitis B vaccine. The
      knowledge scores were significantly higher for students aged over 25 years,
      married or post-graduated (p<0.001). Vaccination coverage against hepatitis B is
      dramatically low among students of health professions in Laos, largely because of
      their lack of knowledge and awareness. Upon admission to the University, all
      future HCWs should receive information about the occupational risks of blood
      borne viruses transmission and be encouraged to get vaccinated against hepatitis
      B. 

PMID- 25066735
TI  - A triple gene mutant of BoHV-1 administered intranasally is significantly more
      efficacious than a BoHV-1 glycoprotein E-deleted virus against a virulent BoHV-1
      challenge.
AB  - Bovine herpesvirus 1 (BoHV-1) causes respiratory infections and abortions in
      cattle, and is an important component of bovine respiratory disease complex,
      which causes a considerable economic loss worldwide. Several efforts have been
      made to produce safer and more effective vaccines. One of these vaccines is a
      glycoprotein E (gE)-deleted marker vaccine which is currently mandated for use in
      EU countries. In the present study, we have constructed a three-gene-mutated BoHV
      1 vaccine virus (UL49.5 luminal domain residues 30-32 and cytoplasmic tail
      residues 80-96 deleted, gE cytoplasmic tail- and entire Us9-deleted) and compared
      its protective vaccine efficacy in calves after intranasal vaccination with that
      of a gE-deleted virus. Following vaccination, both the triple mutant and gE
      deleted vaccine virus replicated well in the nasal epithelium of the calves. The
      vaccinated calves did not show any clinical signs. Four weeks post-vaccination,
      the animals were challenged intranasally with a virulent BoHV-1 wild-type virus.
      Based on clinical signs, both the gE-deleted and triple mutant group were
      protected equally against the virulent BoHV-1 challenge. However, based on the
      quantity and duration of nasal viral shedding, virus neutralizing antibody and
      cellular immune responses, the triple mutant virus vaccine induced a
      significantly better protective immune response than the gE-deleted virus
      vaccine. Notably, after the virulent BoHV-1 challenge, the triple mutant virus
      vaccinated group cleared the challenge virus three days earlier than the BoHV-1
      gE-deleted virus vaccinated group.

PMID- 25066736
TI  - A role for impaired regulatory T cell function in adverse responses to aluminum
      adjuvant-containing vaccines in genetically susceptible individuals.
AB  - Regulatory T cells play a critical role in the immune response to vaccination,
      but there is only a limited understanding of the response of regulatory T cells
      to aluminum adjuvants and the vaccines that contain them. Available studies in
      animal models show that although induced T regulatory cells may be induced
      concomitantly with effector T cells following aluminum-adjuvanted vaccination,
      they are unable to protect against sensitization, suggesting that under the Th2
      immune-stimulating effects of aluminum adjuvants, Treg cells may be functionally
      compromised. Allergic diseases are characterized by immune dysregulation, with
      increases in IL-4 and IL-6, both of which exert negative effects on Treg
      function. For individuals with a genetic predisposition, the beneficial influence
      of adjuvants on immune responsiveness may be accompanied by immune dysregulation,
      leading to allergic diseases. This review examines aspects of the regulatory T
      cell response to aluminum-adjuvanted immunization and possible genetic
      susceptibility factors related to that response. 

PMID- 25066737
TI  - Evaluation of nonspreading Rift Valley fever virus as a vaccine vector using
      influenza virus hemagglutinin as a model antigen.
AB  - Virus replicon particles are capable of infection, genome replication and gene
      expression, but are unable to produce progeny virions, rendering their use
      inherently safe. By virtue of this unique combination of features, replicon
      particles hold great promise for vaccine applications. We previously developed
      replicon particles of Rift Valley fever virus (RVFV) and demonstrated their high
      efficacy as a RVFV vaccine in the natural target species. We have now
      investigated the feasibility of using this nonspreading RVFV (NSR) as a vaccine
      vector using influenza virus hemagglutinin as a model antigen. NSR particles were
      designed to express either the full-length hemagglutinin of influenza A virus
      H1N1 (NSR-HA) or the respective soluble ectodomain (NSR-sHA). The efficacies of
      the two NSR vector vaccines, applied via either the intramuscular or the
      intranasal route, were evaluated. A single vaccination with NSR-HA protected all
      mice from a lethal challenge dose, while vaccination with NSR-sHA was not
      protective. Interestingly, whereas intramuscular vaccination elicited superior
      systemic immune responses, intranasal vaccination provided optimal clinical
      protection. 

PMID- 25066738
TI  - Enhanced immune responses of foot-and-mouth disease vaccine using new oil/gel
      adjuvant mixtures in pigs and goats.
AB  - The immunity and protective capability produced by vaccines can vary remarkably
      according to the kinds of adjuvants being used. In the case of foot-and-mouth
      disease (FMD) vaccines in pigs, only oil-adjuvant vaccines have been used, and
      these tend to show lower immunity in pigs than in cattle. New adjuvants for these
      vaccines are therefore needed. We made different experimental FMD vaccines using
      new adjuvants (ISA 201, Carbigen, Emulsigen-D) and well-known adjuvants (ISA 206,
      aluminum hydroxide gel) and then conducted tests to compare the enhancement in
      pig immunity. More effective immune responses and protection against challenge
      were observed with the new adjuvants Emulsigen-D and ISA 201 compared to existing
      adjuvants. In the case of dairy goats, a mixture of Emulsigen-D and aluminum
      hydroxide gel produced rapid neutralizing antibody responses that were similar to
      results from tests conducted with pigs. 

PMID- 25066739
TI  - Apoptosis of antigen-specific CTLs contributes to low immune response in gut
      associated lymphoid tissue post vaccination.
AB  - The gut-associated lymphoid tissue (GALT) represents a major reservoir of HIV in
      infected individuals. Vaccines can induce strong systemic immune responses but
      these have less impact on CD4 T cells activity and numbers in GALT. In this
      study, we vaccinated mice with an adenovirus vector that expressed the envelope
      gene from HIV and observed immune responses in the peripheral blood, spleen,
      liver, mesenteric lymph nodes, and Peyer's patches. We found that (1) the number
      of HIV-specific CD8 T cells was dramatically lower in GALT than in other tissues;
      (2) the programmed cell death protein-1 (PD-1) was expressed at high levels in
      HIV-specific CD8 T cells including memory T cells in GALT; and (3) high levels of
      HIV-specific CD8 T cell apoptosis were occurring in GALT. These results suggest
      that contributing to GALT becoming an HIV reservoir during infection is a
      combination of exhaustion and/or dysfunction of HIV-specific CTLs at that site.
      These results emphasize the importance of developing of an effective mucosal
      vaccine against HIV.

PMID- 25066741
TI  - Midwives Improving Women's Health Globally: highlights from the International
      Confederation of Midwives 30th Triennial Congress.

PMID- 25066740
TI  - Hyper-attenuated MTBVAC erp mutant protects against tuberculosis in mice.
AB  - Safety of individuals at risk of immune suppression is an important concern for
      live vaccines. The new-generation tuberculosis vaccine candidate MTBVAC, a
      genetically engineered doubly attenuated Mycobacterium tuberculosis mutant with
      deletions in phoP and fadD26 virulence genes has demonstrated comparable safety
      in different relevant animal models and superior protection in mice as compared
      to the only currently licensed tuberculosis vaccine Mycobacterium bovis BCG. Here
      we describe the construction of a highly attenuated MTBVAC-based live vaccine by
      an additional gene inactivation generated in erp of MTBVAC. The gene product of
      erp is an exported repeated protein (Erp), a virulence factor described to be
      involved in intracellular replication of M. tuberculosis. The resultant strain,
      MTBVAC erp(-), was tested in severe combined immunodeficiency (SCID) mouse model
      showing to be severely attenuated when compared to BCG and MTBVAC. Experiments
      conducted in immunocompetent mice revealed that the hyper-attenuated profile
      observed with MTBVAC erp(-) strain did not compromise its protective efficacy
      profile in comparison with BCG. These results postulate MTBVAC erp(-) as a
      potential tuberculosis vaccine candidate for use in high-risk populations of
      immune suppression (e.g., due to HIV infection), where the use of BCG is not
      recommended. 

PMID- 25066742
TI  - Using a life course model to examine racial disparities in low birth weight
      during adolescence and young adulthood.
AB  - INTRODUCTION: This study examined relationships between health, social,
      environmental, and economic factors during adolescence and the subsequent risk of
      giving birth to a low-birth-weight (LBW) infant, to inform strategies for
      reducing racial disparities in LBW. METHODS: Data were derived from the National
      Longitudinal Study of Adolescent Health. A sample of 1213 adolescents, reporting
      on first pregnancies, was created with 35% black, non-Hispanic (black) and 65%
      white, non-Hispanic (white) participants. Independent variables were from the
      domains of individual characteristics, health status, access to care, and social
      environment. The dependent variable was low birth weight. Overall and race
      specific logistic regression models were estimated. RESULTS: Black women had 1.9
      times the odds of giving birth to an LBW infant as white women. Factors
      associated with LBW differed between black women and white women. Black women
      with a history of hypertension were 6 times more likely to have an LBW infant.
      Intimate partner support during prenatal care was protective for black women.
      Factors associated with an increased risk of giving birth to an LBW infant for
      white women included an intergenerational pattern of LBW, low body mass index
      during adolescence, and smoking during pregnancy. Socioeconomic factors during
      adolescence did not predict the odds of having an LBW infant for either group,
      except for white women whose parents had less than a high school education and
      black women living in medium-poverty neighborhoods. DISCUSSION: Findings suggest
      that strategies to reduce racial disparities should address the specific needs of
      the population being served over the life course.

PMID- 25066743
TI  - Breastfeeding and the risk of ovarian cancer: a meta-analysis.
AB  - INTRODUCTION: The aim of this meta-analysis was to assess the association between
      breastfeeding and risk of ovarian cancer. METHODS: Relevant observational studies
      were identified by a search of the MEDLINE and EMBASE databases through December
      2012. Summary odds ratios (ORs) for ovarian cancer, comparing women who had
      breastfed with women who had not, were calculated using a random-effects model. A
      dose-response meta-analysis assessed the risk of ovarian cancer by breastfeeding
      duration. RESULTS: A total of 19 studies were included in the meta-analysis.
      Compared with women who had not breastfed, women who had breastfed had a
      significantly decreased risk of ovarian cancer, with an OR of 0.66 (95% CI, 0.57
      0.76; P < .001). We observed an inverse linear relationship with breastfeeding
      duration: for every one-month increase in breastfeeding, the OR was 0.98 (95% CI,
      0.97-0.99; P < .001). A nonlinear association was also apparent, with a sharp
      decrease in the OR when breastfeeding duration was 8 to 10 months. There was
      evidence of heterogeneity (I(2)  = 83.9%). No publication bias was found (Begg
      test, P = 0.89; Egger test, P = 0.89). DISCUSSION: Breastfeeding reduces the risk
      of ovarian cancer proportional to duration. Breastfeeding for 8 to 10 months may
      be most effective for reducing the risk of ovarian cancer.

PMID- 25066744
TI  - Ongoing professional practice evaluation and focused professional practice
      evaluation: an overview for advanced practice clinicians.

PMID- 25066745
TI  - Mental illness: my personal experience, our professional responsibility.

PMID- 25066746
TI  - Mental illness: my personal experience, our professional responsibility.

PMID- 25066747
TI  - Mental illness: my personal experience, our professional responsibility.

PMID- 25066748
TI  - In reply.

PMID- 25066750
TI  - Fusion of white and gray matter geometry: a framework for investigating brain
      development.
AB  - Current neuroimaging investigation of the white matter typically focuses on
      measurements derived from diffusion tensor imaging, such as fractional anisotropy
      (FA). In contrast, imaging studies of the gray matter oftentimes focus on
      morphological features such as cortical thickness, folding and surface curvature.
      As a result, it is not clear how to combine findings from these two types of
      approaches in order to obtain a consistent picture of morphological changes in
      both gray and white matter. In this paper, we propose a joint investigation of
      gray and white matter morphology by combining geometrical information from white
      and the gray matter. To achieve this, we first introduce a novel method for
      computing multi-scale white matter tract geometry. Its formulation is based on
      the differential geometry of curve sets and is easily incorporated into a
      continuous scale-space framework. We then incorporate this method into a novel
      framework for "fusing" white and gray matter geometrical information. Given a set
      of fiber tracts originating in a particular cortical region, the key idea is to
      compute two scalar fields that represent geometrical characteristics of the white
      matter and of the surface of the cortical region. A quantitative marker is
      created by combining the distributions of these scalar values using Mutual
      Information. This marker can be then used in the study of normal and pathological
      brain structure and development. We apply this framework to a study on autism
      spectrum disorder in children. Our preliminary results support the view that
      autism may be characterized by early brain overgrowth, followed by reduced or
      arrested growth (Courchesne, 2004). 

PMID- 25066749
TI  - Simultaneous and consistent labeling of longitudinal dynamic developing cortical
      surfaces in infants.
AB  - The human cerebral cortex develops extremely dynamically in the first 2years of
      life. Accurate and consistent parcellation of longitudinal dynamic cortical
      surfaces during this critical stage is essential to understand the early
      development of cortical structure and function in both normal and high-risk
      infant brains. However, directly applying the existing methods developed for the
      cross-sectional studies often generates longitudinally-inconsistent results, thus
      leading to inaccurate measurements of the cortex development. In this paper, we
      propose a new method for accurate, consistent, and simultaneous labeling of
      longitudinal cortical surfaces in the serial infant brain MR images. The proposed
      method is explicitly formulated as a minimization problem with an energy function
      that includes a data fitting term, a spatial smoothness term, and a temporal
      consistency term. Specifically, inspired by multi-atlas based label fusion, the
      data fitting term is designed to integrate the contributions from multi-atlas
      surfaces adaptively, according to the similarities of their local cortical
      folding with that of the subject cortical surface. The spatial smoothness term is
      then designed to adaptively encourage label smoothness based on the local
      cortical folding geometries, i.e., allowing label discontinuity at sulcal bottoms
      (which often are the boundaries of cytoarchitecturally and functionally distinct
      regions). The temporal consistency term is to adaptively encourage the label
      consistency among the temporally-corresponding vertices, based on their
      similarity of local cortical folding. Finally, the entire energy function is
      efficiently minimized by a graph cuts method. The proposed method has been
      applied to the parcellation of longitudinal cortical surfaces of 13 healthy
      infants, each with 6 serial MRI scans acquired at 0, 3, 6, 9, 12 and 18months of
      age. Qualitative and quantitative evaluations demonstrated both accuracy and
      longitudinal consistency of the proposed method. By using our method, for the
      first time, we reveal several hitherto unseen properties of the dynamic and
      regionally heterogeneous development of the cortical surface area in the first
      18months of life. 

PMID- 25066752
TI  - A unique architecture based on 1 D semiconductor, reduced graphene oxide, and
      chalcogenide with multifunctional properties.
AB  - A unique heterostructured optoelectronic material (HOM), consisting of a reduced
      graphene oxide (RGO) layer with spatially distributed CdS, suspended by zinc
      oxide (ZnO) nanorods, is presented. The key features of this HOM are the assembly
      of the components in a manner so as to realize an effective integration between
      the constituents and the ability to modify the electronic properties of the RGO.
      For the first time, the location of RGO (as a suspended layer) along with the
      tuning of its charge-transport properties (n-/p-type) and its influence on the
      photo(electro)chemical processes has been examined systematically by using this
      ZnO/RGO/CdS HOM as a case study. The n-type RGO interlayer facilitates >100 %
      increase in the photocurrent density and 25 % increase in the photodegradation of
      a dye, compared to ZnO/CdS, thus demonstrating its multifunctionality. At 3.2 mA
      cm(-2) , this HOM architecture helps to achieve the highest photocurrent density
      utilizing ZnO, RGO, and CdS as building blocks in any form. The work is
      significant for the following reasons: i) other one dimensional (1D)
      oxides/chalcogenides or 1D oxides/dyes may be designed with similar
      architectures; ii) HOMs with tunable optical absorbance and charge-transport
      properties could be realized; iii) related application areas (e.g., sensing or
      solar fuel generation) should be greatly benefited. 

PMID- 25066751
TI  - Sequential determination of serum viral titers, virus-specific IgG antibodies,
      and TNF-alpha, IL-6, IL-10, and IFN-gamma levels in patients with Crimean-Congo
      hemorrhagic fever.
AB  - BACKGROUND: Although there have been a number of studies on the pathogenesis of
      Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still
      insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV)
      titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-6, IL-10, and interferon (IFN)-gamma in CCHF
      patients. METHODS: In total, 31 CCHF cases (11 fatal) were studied. Serum samples
      were obtained daily from all patients from the time of admission and continued
      for a 7-day hospitalization period for serologic (ELISA), virologic (real-time
      PCR), and cytokine (ELISA) analysis. RESULTS: The mean serum CCHFV titer at
      admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in
      survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6
      and TNF-alpha at admission were found to be significantly increased in fatal
      cases. The serum levels of IL-6, TNF-alpha and serum CCHFV titer at admission
      were significantly and positively correlated with disseminated intravascular
      coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r =
      0.625, p = 0.003, respectively). When the data obtained from the sequential
      determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-alpha, IL-10
      and IFN-gamma were grouped according to the days of illness, the initial serum
      CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09
      (copies/mL) in a survivor on the 2 day of illness. While significant alterations
      were observed in all cytokines during the monitoring period, IL-6 levels remained
      consistently higher in fatal cases and TNF-alpha levels increased in both in
      fatal and non-fatal CCHF cases. CONCLUSIONS: The increased CCHFV load and higher
      concentrations of IL-6 and TNF-alpha, the presence of DIC, and the absence of
      CCHFV specific immunity are strongly associated with death in CCHF.

PMID- 25066753
TI  - Salvage of a twisted end to side anastomosis with microvascular coupler.

PMID- 25066754
TI  - Comparison of T1 relaxation times in adipose tissue of severely obese patients
      and healthy lean subjects measured by 1.5 T MRI.
AB  - Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in composition,
      endocrine function and localization in the body. VAT is considered to play a role
      in the pathogenesis of insulin resistance, type 2 diabetes, fatty liver disease,
      and other obesity-related disorders. It has been shown that the amount,
      distribution, and (cellular) composition of adipose tissue (AT) correlate well
      with metabolic conditions. In this study, T1 relaxation times of AT were measured
      in severely obese subjects and compared with those of healthy lean controls.
      Here, we tested the hypothesis that T1 relaxation times of AT differ between lean
      and obese individuals, but also between VAT and SAT as well as superficial (sSAT)
      and deep SAT (dSAT) in the same individual. Twenty severely obese subjects (BMI
      41.4 +/- 4.8 kg/m(2) ) and ten healthy lean controls matched for age (BMI 21.5 +/
      1.9 kg/m(2) ) underwent MRI at 1.5 T using a single-shot fast spin-echo sequence
      (short-tau inversion recovery) at six different inversion times (TI range 100
      1000 ms). T1 relaxation times were computed for all subjects by fitting the TI 
      dependent MR signal intensities of user-defined regions of interest in both SAT
      and VAT to a model function. T1 times in sSAT and dSAT were only measured in
      obese patients. For both obese patients and controls, the T1 times of SAT (275 +/
      14 and 301 +/- 12 ms) were significantly (p < 0.01) shorter than the respective
      values in VAT (294 +/- 20 and 360 +/- 35 ms). Obese subjects also showed
      significant (p < 0.01) T1 differences between sSAT (268 +/- 11 ms) and dSAT (281
      +/- 19 ms). More important, T1 differences in both SAT and VAT were highly
      significant (p < 0.001) between obese patients and healthy subjects. The results
      of our pilot study suggest that T1 relaxation times differ between severely obese
      patients and lean controls, and may potentially provide an additional means for
      the non-invasive assessment of AT conditions and dysfunction.

PMID- 25066755
TI  - Electronic excited state redox properties for BODIPY dyes predicted from Hammett
      constants: estimating the driving force of photoinduced electron transfer.
AB  - Here we formulate equations based solely on empirical Hammett substituent
      constants to predict the redox potentials for the electronic excited state of
      boron-dipyrromethene (BODIPY) dyes. We utilized computational, spectroscopic, and
      electrochemical techniques toward characterizing the effect of substitution at
      the positions C2, C6, and C8 of the 1,3,5,7-tetramethyl BODIPY core. Working with
      a library of 100 BODIPY dyes, we found that highest occupied molecular orbital
      (HOMO) energies calculated at the B3LYP 6-31g(d) level correlated linearly with
      the Hammett sigmam value for substituents at position C8 and with Hammett sigmap
      values for substituents at positions C2 and C6. In turn, we observed that LUMO
      energies correlated linearly with Hammett sigmap at position C8 and with Hammett
      sigmam at positions C2 and C6. Focusing on a subset of 26 dyes for which
      reduction potentials were either previously available or measured herein and
      ranged from -1.84 to -0.52 V (a full 1.3 V), we found a linear relationship
      between redox potentials in acetonitrile and HOMO and lowest unoccupied molecule
      orbital (LUMO) energies determined via density functional theory (DFT). A linear
      correlation was thus ultimately established between redox potentials in
      acetonitrile and Hammett substituent constants. Combining this with equations
      derived for the linear relationship existing between the zero vibrational energy
      of the excited BODIPY and Hammett substituent constants enabled us to provide the
      parameters toward predicting the oxidizing/reducing power of photoexcited
      1,3,5,7,-tetramethyl BODIPY dyes in their singlet excited state. 

PMID- 25066756
TI  - Radiation dose reduction in chest CT--review of available options.
AB  - Computed tomography currently accounts for the majority of radiation exposure
      related to medical imaging. Although technological improvement of CT scanners has
      reduced the radiation dose of individual examinations, the benefit was
      overshadowed by the rapid increase in the number of CT examinations. Radiation
      exposure from CT examination should be kept as low as reasonably possible for
      patient safety. Measures to avoid inappropriate CT examinations are needed.
      Principles and information on radiation dose reduction in chest CT are reviewed
      in this article. The reduction of tube current and tube potential are the
      mainstays of dose reduction methods. Study results indicate that routine
      protocols with reduced tube current are feasible with diagnostic results
      comparable to conventional standard dose protocols. Tube current adjustment is
      facilitated by the advent of automatic tube current modulation systems by setting
      the appropriate image quality level for the purpose of the examination. Tube
      potential reduction is an effective method for CT pulmonary angiography. Tube
      potential reduction often requires higher tube current for satisfactory image
      quality, but may still contribute to significant radiation dose reduction. Use of
      lower tube potential also has considerable advantage for smaller patients.
      Improvement in image production, especially the introduction of iterative
      reconstruction methods, is expected to lower radiation dose significantly.
      Radiation dose reduction in CT is a multifaceted issue. Understanding these
      aspects leads to an optimal solution for various indications of chest CT. 

PMID- 25066757
TI  - Liver X receptor agonist prevents LPS-induced mastitis in mice.
AB  - Liver X receptor-alpha (LXR-alpha) which belongs to the nuclear receptor
      superfamily, is a ligand-activated transcription factor. Best known for its
      ability to regulate lipid metabolism and transport, LXRs have recently also been
      implicated in regulation of inflammatory response. The aim of this study was to
      investigate the preventive effects of synthetic LXR-alpha agonist T0901317 on LPS
      induced mastitis in mice. The mouse model of mastitis was induced by injection of
      LPS through the duct of mammary gland. T0901317 was injected 1h before and 12h
      after induction of LPS intraperitoneally. The results showed that T0901317
      significantly attenuated the infiltration of neutrophilic granulocytes, and the
      activation of myeloperoxidase (MPO); down-regulated the level of pro-inflammatory
      mediators including TNF-alpha, IL-1beta, IL-6, COX-2 and PEG2; inhibited the
      phosphorylation of IkappaB-alpha and NF-kappaB p65, caused by LPS. Moreover, we
      report for the first time that LXR-alpha activation impaired LPS-induced
      mastitis. Taken together, these data indicated that T0901317 had protective
      effect on mastitis and the anti-inflammatory mechanism of T0901317 on LPS induced
      mastitis in mice may be due to its ability to inhibit NF-kappaB signaling
      pathway. LXR-alpha activation can be used as a therapeutic approach to treat
      mastitis. 

PMID- 25066758
TI  - Therapeutic effects of total steroid saponin extracts from the rhizome of
      Dioscorea zingiberensis C.H.Wright in Freund's complete adjuvant induced
      arthritis in rats.
AB  - The aim of our present study is to explore the anti-arthritic potential effect of
      total steroid saponins (TSSNs) extracted from the rhizome of Dioscorea
      zingiberensis C.H.Wright (DZW) and to investigate the underlying mechanisms. This
      work was performed using adjuvant-induced arthritis (AIA) rats in vivo and
      lipopolysaccharide (LPS) simulated 264.7 macrophage cells in vitro. In AIA
      induced arthritic rats, TSSN significantly alleviated the arthritic progression
      through evaluating arthritic score, immune organ indexes, paw swelling, and body
      weight. This phenomenon was well correlated with significant suppression of the
      overproduction of inflammation cytokines (IL-1, IL-1beta, IL-6, and TNF-alpha),
      oxidant stress makers (MDA and NO), eicosanoids (LTB4 and PGE2), and inflammatory
      enzymes (5-LOX and COX-2) versus the AIA rats without treatment. On the contrary,
      the release of SOD and IL-10 was profoundly increased. What's more, TSSN could
      obviously ameliorate the translocation of NF-kappaB to the nucleus through
      phosphorylation of the p65 and IkappaBalpha in vivo and in vitro. The current
      findings demonstrated that TSSN could protect the injured ankle joint from
      further deterioration and exert its satisfactory anti-arthritis properties
      through anti-inflammatory and anti-oxidant effects via inactivating the NF-kappaB
      signal pathway. This research implies that DZW may be a useful therapeutic agent
      for the treatment of human arthritis. 

PMID- 25066759
TI  - CpG-ODN class C-mediated immunostimulation and its potential against Trypanosoma
      evansi in equines.
AB  - Trypanosoma evansi is the causative agent of surra, which is the most common and
      widespread trypansomal disease. The infection is mainly restricted to animals,
      but it has also been documented in human. Trypanosomes possess the thick
      immunogenic surface coat known as variant surface glycoprotein (VSG). The
      parasite modifies the VSG constantly resulting in continuous antigenic variations
      and thus evades the host immune response. Due to antigenic variations,
      vaccination against trypanosomosis is not useful. Therefore, alternate strategies
      to augment the immune response are required. CpG-ODN class-C has combined immune
      effects of both A and B classes of CpG-ODN. In this study, we observed that CpG
      ODN class-C stimulated horse peripheral blood mononuclear cells (PBMC) induce the
      expression of interferon-alpha (IFN-alpha), tumor necrosis factor-alpha (TNF
      alpha), IL-12 and nitric oxide (NO) indicating enhanced innate immune response.
      We have for the first time demonstrated that co-culture of CpG-ODN with T. evansi
      antigen induces lymphocyte proliferative responses and result in a synergistic
      effect in eliciting the immune response. 

PMID- 25066760
TI  - Dynamic analysis of tumor-associated immune cells in DEN-induced rat
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis and
      limited methods to predict patient survival. Immune cells infiltrating tumors are
      known to impact tumor progression. Here, we analyzed the phenotype and function
      of dendritic cells (DCs), and the frequency of IL-10-producing regulatory B cells
      (Breg) and Foxp3(+) regulatory T cells (Treg) in different stages of N
      nitrosodiethylamine (DEN)-induced rat HCC in order to understand their roles in
      this disease. 4weeks following DEN treatment, no significant differences in CD80
      and CD86 expression were found on DCs from HCC rats and normal rats but 12 and
      16weeks following DEN treatment, the expression of CD80, CD86 and MHCII on DCs of
      HCC rats was significantly decreased. We also found that the frequency of IL-10
      producing Breg and CD4(+)CD25(+)Foxp3(+) Treg in HCC rats was obviously increased
      during all of these three stages. In addition, the bone-marrow derived DCs
      (BMDCs) from HCC rats displayed lower ability in activating T cells and an
      increase in IL-10 secretion. No differences in IL-12 level and endocytosis
      ability were found on BMDCs from HCC rats and normal rats. Our results suggest
      that the dysfunction of DCs and the increase of IL-10-producing Breg and Foxp3(+)
      Treg might play important roles in HCC progression. 

PMID- 25066763
TI  - Gunnar Sedin.

PMID- 25066761
TI  - Siegesbeckia glabrescens attenuates allergic airway inflammation in LPS
      stimulated RAW 264.7 cells and OVA induced asthma murine model.
AB  - Siegesbeckia glabrescens (SG) is a plant growing in Korea that is used as a
      traditional medicine for various inflammatory diseases. In this study, we
      investigated the protective effects of SG extract on allergic asthma in an
      ovalbumin (OVA)-induced asthma murine model and lipopolysaccharide (LPS)
      stimulated RAW264.7 cells. Female BALB/c mice were sensitized by intraperitoneal
      injection of OVA on days 0 and 14 and then challenged with OVA from days 21 to
      23. SG (30mg/kg) was administered by oral gavage 1h before the OVA challenge. LPS
      stimulated RAW264.7 cells were evaluated to determine their levels of nitric
      oxide (NO). The SG significantly reduced the number of inflammatory cells in
      bronchoalveolar lavage (BAL) fluid and also reduced IL-4, IL-5, IL-13, eotaxin
      and immunoglobulin E in OVA-sensitized/challenged mice. SG also effectively
      reduced airway inflammation and mucus overproduction in lung tissue in addition
      to decreasing the expression of iNOS and COX-2. In LPS-stimulated RAW264.7 cells,
      SG treatment significantly reduced the levels of NO. These findings indicate that
      SG effectively suppressed inflammatory responses, and its effects appear to be
      related to reduction in iNOS and COX-2 expression. Therefore, we suggest that SG
      may have potential use as a therapeutic agent for inflammatory diseases such as
      allergic asthma. 

PMID- 25066764
TI  - Meaningful use: how did we do, where are we now, where do we go from here?

PMID- 25066765
TI  - Pediatric glaucoma surgery: a report by the American Academy Of Ophthalmology.
AB  - OBJECTIVE: To review the current published literature to evaluate the success
      rates and long-term problems associated with surgery for pediatric glaucoma.
      METHODS: Literature searches of the PubMed and Cochrane Library databases were
      last conducted in May 2012. The search yielded 838 potentially relevant
      citations, of which 273 were in non-English languages. The titles and abstracts
      of these articles were reviewed by the authors, and 364 were selected for
      possible further review. Members of the Ophthalmic Technology Assessment
      Committee Glaucoma Panel reviewed the full text of these articles and used the 36
      that met inclusion and exclusion criteria for this Ophthalmic Technology
      Assessment. There were no studies on the topic that provided level I evidence.
      The assessment included only level II and level III studies. RESULTS: Surgeons
      treat pediatric glaucoma most commonly with goniotomy, trabeculotomy,
      trabeculectomy, combined trabeculotomy and trabeculectomy, tube shunt surgery,
      cyclodestruction, and deep sclerectomy. Certain surgical options seem better for
      specific diagnoses, such as primary congenital glaucoma, aphakic glaucoma, and
      glaucomas associated with other ocular or systemic anomalies. CONCLUSIONS: There
      are many surgical options for the treatment of the pediatric glaucomas. The
      relative efficacy of these various procedures for particular diagnoses and
      clinical situations should be weighed against the specific risks associated with
      the procedures for individual patients.

PMID- 25066766
TI  - Integrating fragmented evidence by network meta-analysis: relative effectiveness
      of psychological interventions for adults with post-traumatic stress disorder.
AB  - BACKGROUND: To summarize the available evidence on the effectiveness of
      psychological interventions for patients with post-traumatic stress disorder
      (PTSD). METHOD: We searched bibliographic databases and reference lists of
      relevant systematic reviews and meta-analyses for randomized controlled trials
      that compared specific psychological interventions for adults with PTSD symptoms
      either head-to-head or against control interventions using non-specific
      intervention components, or against wait-list control. Two investigators
      independently extracted the data and assessed trial characteristics. RESULTS: The
      analyses included 4190 patients in 66 trials. An initial network meta-analysis
      showed large effect sizes (ESs) for all specific psychological interventions (ESs
      between -1.10 and -1.37) and moderate effects of psychological interventions that
      were used to control for non-specific intervention effects (ESs -0.58 and -0.62).
      ES differences between various types of specific psychological interventions were
      absent to small (ES differences between 0.00 and 0.27). Considerable between
      trial heterogeneity occurred (tau2= 0.30). Stratified analyses revealed that
      trials that adhered to DSM-III/IV criteria for PTSD were associated with larger
      ESs. However, considerable heterogeneity remained. Heterogeneity was reduced in
      trials with adequate concealment of allocation and in large-sized trials. We
      found evidence for small-study bias. CONCLUSIONS: Our findings show that patients
      with a formal diagnosis of PTSD and those with subclinical PTSD symptoms benefit
      from different psychological interventions. We did not identify any intervention
      that was consistently superior to other specific psychological interventions.
      However, the robustness of evidence varies considerably between different
      psychological interventions for PTSD, with most robust evidence for cognitive
      behavioral and exposure therapies.

PMID- 25066767
TI  - The role of calcium and cyclic nucleotide signaling in cerebellar granule cell
      migration under normal and pathological conditions.
AB  - In the developing brain, immature neurons migrate from their sites of origin to
      their final destination, where they reside for the rest of their lives. This
      active movement of immature neurons is essential for the formation of normal
      neuronal cytoarchitecture and proper differentiation. Deficits in migration
      result in the abnormal development of the brain, leading to a variety of
      neurological disorders. A myriad of extracellular guidance molecules and
      intracellular effector molecules is involved in controlling the migration of
      immature neurons in a cell type, cortical layer and birth-date-specific manner.
      To date, little is known about how extracellular guidance molecules transfer
      their information to the intracellular effector molecules, which regulate the
      migration of immature neurons. In this article, to fill the gap between
      extracellular guidance molecules and intracellular effector molecules, using the
      migration of cerebellar granule cells as a model system of neuronal cell
      migration, we explore the role of second messenger signaling (specifically Ca(2+)
      and cyclic nucleotide signaling) in the regulation of neuronal cell migration. We
      will, first, describe the cortical layer-specific changes in granule cell
      migration. Second, we will discuss the roles of Ca(2+) and cyclic nucleotide
      signaling in controlling granule cell migration. Third, we will present recent
      studies showing the roles of Ca(2+) and cyclic nucleotide signaling in the
      deficits in granule cell migration in mouse models of fetal alcohol spectrum
      disorders and fetal Minamata disease.

PMID- 25066768
TI  - The CentriMag centrifugal blood pump as a benchmark for in vitro testing of
      hemocompatibility in implantable ventricular assist devices.
AB  - Implantable ventricular assist devices (VADs) have proven efficient in advanced
      heart failure patients as a bridge-to-transplant or destination therapy. However,
      VAD usage often leads to infection, bleeding, and thrombosis, side effects
      attributable to the damage to blood cells and plasma proteins. Measuring
      hemolysis alone does not provide sufficient information to understand total blood
      damage, and research exploring the impact of currently available pumps on a wider
      range of blood cell types and plasma proteins such as von Willebrand factor (vWF)
      is required to further our understanding of safer pump design. The extracorporeal
      CentriMag (Thoratec Corporation, Pleasanton, CA, USA) has a hemolysis profile
      within published standards of normalized index of hemolysis levels of less than
      0.01 g/100 L at 100 mm Hg but the effect on leukocytes, vWF multimers, and
      platelets is unknown. Here, the CentriMag was tested using bovine blood (n = 15)
      under constant hemodynamic conditions in comparison with a static control for
      total blood cell counts, hemolysis, leukocyte death, vWF multimers,
      microparticles, platelet activation, and apoptosis. The CentriMag decreased the
      levels of healthy leukocytes (P < 0.006), induced leukocyte microparticles (P <
      10(-5) ), and the level of high molecular weight of vWF multimers was
      significantly reduced in the CentriMag (P < 10(-5) ) all compared with the static
      treatment after 6 h in vitro testing. Despite the leukocyte damage, microparticle
      formation, and cleavage of vWF multimers, these results show that the CentriMag
      is a hemocompatible pump which could be used as a standard in blood damage assays
      to inform the design of new implantable blood pumps. 

PMID- 25066770
TI  - Probing the surface of colloidal nanomaterials with potentiometry in situ.
AB  - Colloidal nanomaterials represent an important branch of modern chemistry.
      However, we have very little understanding of molecular processes that occur at
      the nanocrystal (NC) surface during synthesis and post-synthetic modifications.
      Here we show that potentiometry can be used to study the surface of colloidal NCs
      under realistic reaction conditions. Potentiometric titrations of CdSe and InP
      nanostructures provide information on the active surface area, the affinity of
      ligands to the NC surface, and the surface reaction kinetics. These studies can
      be carried out at different temperatures in polar and nonpolar media for NCs of
      different sizes and shapes. In situ potentiometry can provide real-time feedback
      during synthesis of core-shell nanostructures. 

PMID- 25066769
TI  - beta-Asarone (cis-2,4,5-trimethoxy-1-allyl phenyl), attenuates pro-inflammatory
      mediators by inhibiting NF-kappaB signaling and the JNK pathway in LPS activated
      BV-2 microglia cells.
AB  - Acorus species contains diverse pharmacologically active phytochemicals including
      alpha-asarone, beta-asarone, and eugenol. We determined if beta-asarone isolated
      from Acorus gramineus (AG) Solander would be efficacious in protecting BV-2
      microglia cells from lipopolysaccharide (LPS)-induced stress signaling. BV-2
      microglial cells were pretreated with an AG ethanol extract (1, 10, and 100
      MUg/mL) or beta-asarone (10, 50, and 100 MUM) prior to exposure to LPS (100
      ng/mL). AG and beta-asarone inhibited LPS-induced production of nitric oxide in a
      dose-dependent manner. The mRNA and protein levels of inducible nitric oxide
      synthase and cyclooxygenase-2 also decreased dose dependently following AG and
      beta-asarone treatments. Immunostaining and immunoblot studies revealed that beta
      asarone also suppressed nuclear factor (NF)-kappaB activation by blocking IkB
      degradation. Further mechanistic studies revealed that beta-asarone acted through
      the JNK/MAPK pathway. Taken together, our findings demonstrate that beta-asarone
      exhibits anti-inflammatory effects by suppressing the production of pro
      inflammatory mediators through NF-kappaB signaling and the JNK pathways in
      activated microglial cells and might be developed as a promising candidate to
      treat various neuroinflammatory diseases.

PMID- 25066771
TI  - Identification of a soft tissue filler by ex vivo confocal microscopy and Raman
      spectroscopy in a case of adverse reaction to the filler.
AB  - BACKGROUND: Soft tissue fillers are usually identified in the skin using the
      conventional histopathologic examination. Ex vivo RCM has been used in one case
      and Raman spectroscopy (RS), which has been recently applied for the
      identification of skin foreign bodies, has never been employed for fillers. We
      report the use of both these new techniques, ex vivo RCM and RS, to confirm the
      diagnosis of adverse reaction to a soft tissue filler and to identify its
      composition. METHODS: We excised a skin nodule suspicious of adverse reaction to
      soft tissue filler, and we performed an ex vivo reflectance confocal microscopy
      (RCM) and an histopathologic examination, followed by a RS analysis. RESULTS: Ex
      vivo RCM showed numerous hypo-reflective microspheres in the dermis that
      corresponded to rounded vacuoles at histopathologic examination, suggestive of
      polymethylmethacrylate (PMMA). RS showed a series of peaks at 600, 813, 970 1252,
      1450, 1728, and 2951 cm(-1) in correspondence to the microspheres, confirming the
      presence of PMMA. CONCLUSION: These results suggest that ex vivo RCM and RS are
      additional tools to conventional histopathologic examination to characterize soft
      tissue fillers in case of adverse reaction. RCM has the advantage compared with
      the histopathologic examination that can be extemporaneously performed on a fresh
      surgical specimen. RS allow a precise chemical identification of the filler.

PMID- 25066773
TI  - Comparing different knowledge sources for the automatic summarization of
      biomedical literature.
AB  - OBJECTIVE: Automatic summarization of biomedical literature usually relies on
      domain knowledge from external sources to build rich semantic representations of
      the documents to be summarized. In this paper, we investigate the impact of the
      knowledge source used on the quality of the summaries that are generated.
      MATERIALS AND METHODS: We present a method for representing a set of documents
      relevant to a given biological entity or topic as a semantic graph of domain
      concepts and relations. Different graphs are created by using different
      combinations of ontologies and vocabularies within the UMLS (including GO, SNOMED
      CT, HUGO and all available vocabularies in the UMLS) to retrieve domain concepts,
      and different types of relationships (co-occurrence and semantic relations from
      the UMLS Metathesaurus and Semantic Network) are used to link the concepts in the
      graph. The different graphs are next used as input to a summarization system that
      produces summaries composed of the most relevant sentences from the original
      documents. RESULTS AND CONCLUSIONS: Our experiments demonstrate that the choice
      of the knowledge source used to model the text has a significant impact on the
      quality of the automatic summaries. In particular, we find that, when summarizing
      gene-related literature, using GO, SNOMED-CT and HUGO to extract domain concepts
      results in significantly better summaries than using all available vocabularies
      in the UMLS. This finding suggests that successful biomedical summarization
      requires the selection of the appropriate knowledge source, whose coverage,
      specificity and relations must be in accordance to the type of the documents to
      summarize.

PMID- 25066774
TI  - Synthesis, in vitro evaluation, and molecular docking studies of azetidinones and
      thiazolidinones of 2-amino-5-cyclopropyl-1,3,4-thiadiazole as antibacterial
      agents.
AB  - In an attempt to find a new class of antimicrobial agents, a series of novel
      azetidin-2-ones 3a-e and thiazolidin-4-ones 4a-e of 2-amino-5-cyclopropyl-1,3,4
      thiadiazole were synthesized. The synthesized compounds were confirmed by melting
      point, IR, (1) H NMR, (13) C NMR, and mass spectroscopy. The beta-lactam
      derivative (3e) was found to be the most potent compound of the series displaying
      excellent antibacterial activities against Staphylococcus aureus, Bacillus
      subtilis, Escherichia coli, and Pseudomonas aeruginosa with MIC values of 15.60,
      31.50, 62.50, and 125 ug/mL, respectively, as compared to the positive control
      drug ampicillin. Molecular docking studies and determination of the leakage of
      UV260 - and UV280 -absorbing material (nucleic acid material and protein)
      confirmed that the synthesized compounds inhibit cell wall synthesis by
      inhibiting PTB (transpeptidase enzyme). Lipinski's rule and in silico ADME
      pharmacokinetic parameters are within the acceptable range defined for human use,
      thereby indicating their potential as a drug-like molecules.

PMID- 25066776
TI  - Dynamic perfusion and diffusion MRI of cortical spreading depolarization in
      photothrombotic ischemia.
AB  - Cortical spreading depolarization (CSD) is known to exacerbate ischemic damage,
      as the number of CSDs correlates with the final infarct volumes and suppressing
      CSDs improves functional outcomes. To investigate the role of CSD in ischemic
      damage, we developed a novel rat model of photothrombotic ischemia using a
      miniature implantable optic fiber that allows lesion induction inside the
      magnetic resonance imaging (MRI) scanner. We were able to precisely control the
      location and the size of the ischemic lesion, and continuously monitor dynamic
      perfusion and diffusion MRI signal changes at high temporal resolution before,
      during and after the onset of focal ischemia. Our model showed that apparent
      diffusion coefficient (ADC) and cerebral blood flow (CBF) in the ischemic core
      dropped immediately after lesion onset by 20+/-6 and 41+/-23%, respectively, and
      continually declined over the next 5h. Meanwhile, CSDs were observed in all
      animals (n=36) and displayed either a transient decrease of ADC by 17+/-3% or an
      increase of CBF by 104+/-15%. All CSDs were initiated from the rim of the
      ischemic core, propagated outward, and confined to the ipsilesional cortex.
      Additionally, we demonstrated that by controlling the size of perfusion-diffusion
      mismatch (which approximates the penumbra) in our model, the number of CSDs
      correlated with the mismatch area rather than the final infarct volume. This
      study introduces a novel platform to study CSDs in real-time with high
      reproducibility using MRI. 

PMID- 25066775
TI  - Establishment and operation of a Good Manufacturing Practice-compliant allogeneic
      Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV
      associated lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV) is associated with several malignancies, including post
      transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD
      are often successful, but risk organ rejection and cause significant side
      effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from
      peripheral blood lymphocytes provide an alternative treatment modality with few
      side effects, but autologous CTLs are difficult to use in clinical practice. Here
      we report the establishment and operation of a bank of EBV-specific CTLs derived
      from 25 blood donors with human leucocyte antigen (HLA) types found at high
      frequency in European populations. Since licensure, there have been enquiries
      about 37 patients, who shared a median of three class I and two class II HLA
      types with these donors. Cells have been infused into ten patients with
      lymphoproliferative disease, eight of whom achieved complete remission. Neither
      patient with refractory disease was matched for HLA class II. Both cases of EBV
      associated non-haematopoietic sarcoma receiving cells failed to achieve complete
      remission. Thirteen patients died before any cells could be issued, emphasizing
      that the bank should be contacted before patients become pre-terminal. Thus, this
      third party donor-derived EBV-specific CTL cell bank can supply most patients
      with appropriately matched cells and most recipients have good outcomes. 

PMID- 25066778
TI  - Enterocytozoon bieneusi, giardia, and Cryptosporidium infecting white-tailed
      deer.
AB  - Despite a white-tailed deer (WTD) population in the United States of
      approximately 32 million animals extremely little is known of the prevalence and
      species of the protists that infect these animals. This study was undertaken to
      determine the presence of potential human protist pathogens in culled WTD in
      central Maryland. Feces from fawns to adults were examined by molecular methods.
      The prevalence of Enterocytozoon bieneusi, Cryptosporidium, and Giardia was
      determined by PCR. All PCR-positive specimens were sequenced to determine the
      species and genotype(s). Of specimens from 80 WTD, 26 (32.5%) contained 17
      genotypes of E. bieneusi. Four genotypes were previously reported (I, J, WL4,
      LW1) and 13 novel genotypes were identified and named DeerEb1-DeerEb13. Genotypes
      I, J, and LW1 are known to infect humans. Ten (12.5%) specimens contained the
      Cryptosporidium deer genotype, and one (1.25%) contained Giardia duodenalis
      Assemblage A. The identification zoonotic G. duodenalis Assemblage A as well as
      four E. bieneusi genotypes previously identified in humans suggest that WTD could
      play a role in the transmission of those parasites to humans. 

PMID- 25066777
TI  - Hepatic inflammation and fibrosis: functional links and key pathways.
AB  - Inflammation is one of the most characteristic features of chronic liver disease
      of viral, alcoholic, fatty, and autoimmune origin. Inflammation is typically
      present in all disease stages and associated with the development of fibrosis,
      cirrhosis, and hepatocellular carcinoma. In the past decade, numerous studies
      have contributed to improved understanding of the links between hepatic
      inflammation and fibrosis. Here, we review mechanisms that link inflammation with
      the development of liver fibrosis, focusing on the role of inflammatory mediators
      in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis
      and fibrosis regression. We will summarize the contributions of different
      inflammatory cells, including hepatic macrophages, T and B lymphocytes, natural
      killer cells and platelets, as well as key effectors, such as cytokines,
      chemokines, and damage-associated molecular patterns. Furthermore, we will
      discuss the relevance of inflammatory signaling pathways for clinical liver
      disease and for the development of antifibrogenic strategies.

PMID- 25066780
TI  - Characterization of investigators' approach to translational research: a
      qualitative study.
AB  - BACKGROUND: Little is known about how investigators approach their research
      programs along the translational research continuum. Many consider the
      translational continuum to be linear, with research beginning at the bench and
      concluding with research at the bedside or in the community. We aimed to
      understand if translational investigators approach and view their research in
      this fashion. METHODS: We conducted semistructured individual interviews with 16
      graduates of the University of Pittsburgh's Multidisciplinary Clinical Research
      Scholars Program (KL2) in 2012. RESULTS: Our research revealed three
      characteristic models. The first model we called "linear" and represented the
      traditional approach. The second we called "holistic"; these investigators began
      with central research questions and sought to explore them in every direction of
      translation, not necessarily taking linear steps. The third model we called
      "technical"; in this model, investigators focused on a unique technology or
      methodology and applied it across multiple research contexts. CONCLUSION: This
      study found that there are multiple ways that translational investigators
      approach their research program. Better understanding of these models can help
      educators and mentors guide investigators so that they can be more productive in
      their clinical or translational research career.

PMID- 25066779
TI  - Resting-state brain function in schizophrenia and psychotic bipolar probands and
      their first-degree relatives.
AB  - BACKGROUND: Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share
      considerable overlap in clinical features, genetic risk factors and co-occurrence
      among relatives. The common and unique functional cerebral deficits in these
      disorders, and in unaffected relatives, remain to be identified. METHOD: A total
      of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first
      degree relatives (38 and 28, respectively) were studied using resting-state
      functional magnetic resonance imaging (rfMRI). Regional cerebral function was
      evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas
      with ALFF alterations were used as seeds in whole-brain functional connectivity
      analysis. We then tested whether abnormalities identified in probands were
      present in unaffected relatives. RESULTS: SCZ and PBD probands both demonstrated
      regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well
      as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands
      showed greater and more widely distributed ALFF alterations including the
      thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was
      related to positive symptoms and cognitive deficit. PBD patients showed uniquely
      increased functional connectivity between the thalamus and bilateral insula. Only
      PBD relatives showed abnormal connectivity within striatal-thalamo-cortical
      networks seen in both proband groups. CONCLUSIONS: The present findings reveal a
      common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and
      unique regional and functional connectivity abnormalities that distinguish them.
      The abnormal network connectivity in PBD relatives that was present in both
      proband groups may reflect genetic susceptibility associated with risk for
      psychosis, but within-family associations of this measure were not high.

PMID- 25066781
TI  - Cigarette smoking among intimate partner violence perpetrators and victims:
      findings from the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - BACKGROUND AND OBJECTIVES: Cigarette smoking and intimate partner violence (IPV)
      are preventable, major public health issues that result in severe physical and
      psychological consequences. The primary aim of the current study was to examine
      the consistency and strength of the association between these highly variable
      behaviors using a nationally representative sample. METHODS: Self-reported IPV
      perpetration, victimization, and smoking data were collected from 25,515 adults
      (54% female) through the National Epidemiologic Survey on Alcohol and Related
      Conditions. Multinomial logistic regression models were constructed to determine
      the relationships among smoking status (current daily, intermittent, former, and
      never smoker) and IPV (minor and sever victimization as well as perpetration).
      RESULTS: Results indicated a robust relationship between IPV and smoking among
      both victims and perpetrators. The odds for current daily and intermittent
      smoking were significantly elevated among those who reported both minor and
      severe IPV relative to their non-violent counterparts. Mood and anxiety disorders
      were significant comorbid conditions in the interpretation of the relationship
      between severe IPV and smoking. CONCLUSIONS: The current study provides strong
      evidence for a robust relationship between IPV and smoking across current smoking
      patterns, IPV severity levels, and IPV experience patterns. SCIENTIFIC
      SIGNIFICANCE: Findings emphasize the need to better understand the mechanisms by
      which smoking and IPV are associated and how this interdependence may impact
      approaches to treatment. Specifically, research is required to assess the
      efficacy of integrated smoking cessation and IPV treatment or recovery programs
      over more traditional, exclusive approaches.

PMID- 25066782
TI  - Stability of cell-free DNA from maternal plasma isolated following a single
      centrifugation step.
AB  - OBJECTIVE: Cell-free fetal DNA can be used for prenatal testing with no procedure
      related risk to the fetus. However, yield of fetal DNA is low compared with
      maternal cell-free DNA fragments, resulting in technical challenges for some
      downstream applications. To maximize the fetal fraction, careful blood processing
      procedures are essential. We demonstrate that fetal fraction can be preserved
      using a single centrifugation step followed by postage of plasma to the
      laboratory for further processing. METHODS: Digital PCR was used to quantify
      copies of total, maternal, and fetal DNA present in single-spun plasma at time
      points over a two-week period, compared with immediately processed double-spun
      plasma, with storage at room temperature, 4 degrees C, and -80 degrees C
      representing different postage scenarios. RESULTS: There was no significant
      change in total, maternal, or fetal DNA copy numbers when single-spun plasma
      samples were stored for up to 1 week at room temperature and 2 weeks at -80
      degrees C compared with plasma processed within 4 h. Following storage at 4
      degrees C no change in composition of cell-free DNA was observed. CONCLUSIONS:
      Single-spun plasma can be transported at room temperature if the journey is
      expected to take one week or less; shipping on dry ice is preferable for longer
      journeys.

PMID- 25066783
TI  - Letter to the Editor: Cannabis use and transition to psychosis: is interpretation
      of unpleasant effects a mediating variable?

PMID- 25066784
TI  - The role and limitations of CAM use in children and adolescents with cancer:
      let's take a look beyond prevalence rates.

PMID- 25066785
TI  - Probiotics as cheater cells: parameter space clustering for individualized
      prescription.
AB  - Clinicians often perform infection management administering probiotics along with
      antibiotics. Such probiotics added to an infecting population showing antibiotic
      resistance can be compared to a dynamical system composed of cheaters and
      workers. The presence of cheater strains is known to modulate the fitness of the
      infecting population. We propose a model where probiotics as cheater strain re
      establishes the susceptibility of a resistant population towards an antibiotic.
      Control parameters must assume optimal values in order to attain minimum worker
      number within a finite time-scale feasible in a clinical set-up. The problem is
      made non-trivial by the complicated interplay between parameters. The model is an
      extension of a logistic framework, where a pay-off function has been included to
      account for the effect of instantaneous worker number on death rates of each
      species. The outcomes for a randomized set of parameter values and initial
      conditions are utilized in partitioning the set and desired clusters were
      identified. For a test case, one can take random combinations of controllable
      parameters and combine them with fixed parameters and find out the closeness of
      the points to the desired cluster centroids. This process leads to the
      identification of optimum antibiotic versus probiotic dosage range leading to
      elimination or limited existence of the genetically resistant population. 

PMID- 25066786
TI  - Allee effects and species co-existence in an environment where resource abundance
      varies.
AB  - Explaining patterns of diversity has long been a central focus in ecology. One of
      the most challenging problems has been to understand how species occupying
      similar ecological niches can co-exist because, with limited resources,
      demographic stochasticity is expected to lead to the eventual extinction of all
      but one of them. The Allee effect has been widely studied for its impact on the
      extinction risk of rare species. Its potential role in promoting co-existence has
      received less attention. Here, we present a model in which two species compete
      for a single resource across a continuous landscape. We show that Allee effects
      can promote their co-existence when a simple condition is met: resources are
      distributed unevenly across space. Furthermore, the Allee effect can stabilize co
      existence despite the reduction in population density and consequent increase in
      demographic stochasticity that it causes. The Allee effect might, therefore, be
      an important force maintaining diverse communities. 

PMID- 25066787
TI  - Ventricular fibrillation mechanisms and cardiac restitutions: An investigation by
      simulation study on whole-heart model.
AB  - BACKGROUND: The action potential duration (APD) and the conduction velocity (CV)
      restitution have been reported to be important in the maintenance and conversion
      of ventricular fibrillation (VF), whose mechanisms remain poorly understood.
      Multiple-wavelet and/or mother-rotor have been regarded as the main VF
      mechanisms, and APD restitution (APDR) and CV restitution (CVR) properties are
      involved in the mutual conversion or transition between VF and ventricular
      tachycardia (VT). METHODS AND RESULTS: The effects of APDR (both its slope and
      heterogeneity) and CVR on VF organization and conversion were examined using a
      "rule-based" whole-heart model. The results showed that different organizations
      of simulated VF were manifestations of different restitution configurations.
      Multiple-wavelet and mother-rotor VF mechanisms could recur in models with steep
      and heterogeneous APDR, respectively. Suppressing the excitability either
      decreased or increased the VF complexity under the steep or shallow APDR,
      respectively. The multiple-wavelet VF changed into a VT in response to a
      flattening of the APDR, and the VT degenerated into a mother-rotor VF due to the
      APDR heterogeneity. CONCLUSIONS: Our results suggest that the mechanisms of VF
      are tightly related to cardiac restitution properties. From a viewpoint of the
      "rule-based" whole-heart model, our work supports the hypothesis that the synergy
      between APDR and CVR contributes to transitions between multiple-wavelet and
      mother-rotor mechanisms in the VF.

PMID- 25066788
TI  - A comparison of automatic and intentional instructions when using the method of
      vanishing cues in acquired brain injury.
AB  - Thirty-four participants with acquired brain injury learned word lists under two
      forms of vanishing cues - one in which the learning trial instructions encouraged
      intentional retrieval (i.e., explicit memory) and one in which they encouraged
      automatic retrieval (which encompasses implicit memory). The automatic
      instructions represented a novel approach in which the cooperation of
      participants was actively sought to avoid intentional retrieval. Intentional
      instructions resulted in fewer errors during the learning trials and better
      performance on immediate and delayed retrieval tests. The advantage of
      intentional over automatic instructions was generally less for those who had more
      severe memory and/or executive impairments. Most participants performed better
      under intentional instructions on both the immediate and the delayed tests.
      Although those who were more severely impaired in both memory and executive
      function also did better with intentional instructions on the immediate retrieval
      test, they were significantly more likely to show an advantage for automatic
      instructions on the delayed test. It is suggested that this pattern of results
      may reflect impairments in the consolidation of intentional memories in this
      group. When using vanishing cues, automatic instructions may be better for those
      with severe consolidation impairments, but otherwise intentional instructions may
      be better. 

PMID- 25066789
TI  - Antimetabolites in cataract surgery to prevent failure of a previous
      trabeculectomy.
AB  - BACKGROUND: Patients having cataract surgery have often earlier undergone a
      trabeculectomy for glaucoma. However, cataract surgery may be associated with
      failure of the previous glaucoma surgery and antimetabolites may be used with
      cataract surgery to prevent such failure. There is no systematic review on
      whether antimetabolites with cataract surgery prevent failure of a previous
      trabeculectomy. OBJECTIVES: To assess the effects of antimetabolites with
      cataract surgery on functioning of a previous trabeculectomy. SEARCH METHODS: We
      searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (2014, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non
      Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June
      2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health
      Sciences Literature Database (LILACS) (January 1982 to June 2014), the
      metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization
      (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 10 June 2014. We also searched the Science Citation Index database (July 2013)
      and reference lists of potentially relevant studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) of antimetabolites with cataract surgery in
      people with a functioning trabeculectomy. DATA COLLECTION AND ANALYSIS: Two
      review authors independently reviewed the titles and abstracts from the
      electronic searches. Two review authors independently assessed relevant full-text
      articles and entered data. MAIN RESULTS: We identified no RCTs to test the
      effectiveness of antimetabolites with cataract surgery in individuals with the
      intention of preventing failure of a previous trabeculectomy. AUTHORS'
      CONCLUSIONS: There are no RCTs of antimetabolites with cataract surgery in people
      with a functioning trabeculectomy. Appropriately powered RCTs are needed of
      antimetabolites during cataract surgery in patients with a functioning
      trabeculectomy.

PMID- 25066790
TI  - Are illness perceptions related to future healthcare expenditure in patients with
      somatoform disorders?
AB  - BACKGROUND: Somatoform disorders are costly for society in terms of increased
      healthcare expenditure. Patients' illness perceptions have been found to play a
      role in somatoform disorders. However, it is unclear whether illness perceptions
      predict higher health costs in these patients. METHOD: A total of 1785 primary
      care patients presenting a new health complaint completed a questionnaire on
      their illness perceptions and emotional distress before the consultation. The
      physicians completed a questionnaire for each patient on diagnostics after the
      consultation. In a stratified subsample, physician interviewers established
      diagnoses of DSM-IV somatization and undifferentiated somatoform disorders (n =
      144) using the Schedules for Clinical Assessment in Neuropsychiatry. Healthcare
      expenditure was obtained from Danish health registers for a 2-year follow-up
      period. RESULTS: Patients had more negative perceptions of their well-defined
      physical health problems when they had a co-morbid somatoform disorder. A strong
      illness identity [beta = 0.120, 95% confidence interval (CI) 0.029-0.212, p =
      0.012], perceived negative consequences (beta = 0.010, 95% CI 0.001-0.019, p =
      0.024), a long timeline perspective (beta = 0.013, 95% CI 0.005-0.021, p =
      0.001), low personal control (beta = - 0.009, 95% CI -0.015 to -0.002, p = 0.011)
      and negative emotional representations (beta = 0.009, 95% CI 0.002-0.017, p =
      0.020) predicted healthcare expenditure in somatoform disorders. CONCLUSIONS: The
      results suggest that illness perceptions play a role in the perpetuation of
      symptoms in somatoform disorders and predict higher future healthcare expenditure
      among a subgroup of these patients.

PMID- 25066791
TI  - Copper subtype of Alzheimer's disease (AD): meta-analyses, genetic studies and
      predictive value of non-ceruloplasmim copper in mild cognitive impairment
      conversion to full AD.
AB  - Alzheimer's disease (AD) is the most common form of dementia. A myriad of complex
      factors contribute to AD, promoting the deposition in plaques of amyloid-beta
      (Abeta), which is the main constituent of this pathognomonic sign of AD at
      autopsy brain inspection. Abeta toxicity is related to oxidative stress, which
      results in synaptic loss in specific brain areas, eventually leading to cognitive
      decline. Metal, and especially copper, dyshomeostasis is a key factor in these
      processes. Recent studies have demonstrated that the serum fraction of copper
      that is not bound to ceruloplasmin (Non-Cp copper, also known as 'free' or labile
      copper) increases in a percentage of AD patients and mild cognitive impairment
      (MCI) subjects; this is considered a precursor of AD. Non-Cp copper is the
      exchangeable fraction of low molecular weight copper in serum. It is
      distinguished from the copper structurally bound to the ceruloplasmin protein, a
      master protein of iron metabolism. Non-Cp copper levels are higher than normal
      reference values (range 0-1.6MUmol/L) in about 50% of amnestic MCI subjects and
      60% of AD patients, typifying them in a subset of AD. Meta-analyses, genetic
      studies and a prognostic study evaluating the predictive value of Non-Cp copper
      in MCI conversion to full AD demonstrate the existence of this copper phenotype
      of AD. 

PMID- 25066792
TI  - Does treatment of schizophrenia with antipsychotic medications eliminate or
      reduce psychosis? A 20-year multi-follow-up study.
AB  - BACKGROUND: This research assesses whether multi-year treatment with
      antipsychotic medications reduces or eliminates psychosis in schizophrenia. It
      provides 20 years of longitudinal data on the frequency and severity of psychotic
      activity in samples of schizophrenia patients (SZ) treated versus those not
      treated with antipsychotic medications. METHOD: A total of 139 early young
      schizophrenia and mood-disordered patients were assessed at index hospitalization
      and then reassessed six times over 20 years for psychosis and other major
      variables. RESULTS: At each follow-up assessment over the 20 years, a
      surprisingly high percentage of SZ treated with antipsychotics longitudinally had
      psychotic activity. More than 70% of SZ continuously prescribed antipsychotics
      experienced psychotic activity at four or more of six follow-up assessments over
      20 years. Longitudinally, SZ not prescribed antipsychotics showed significantly
      less psychotic activity than those prescribed antipsychotics (p < 0.05).
      CONCLUSIONS: The 20-year data indicate that, longitudinally, after the first few
      years, antipsychotic medications do not eliminate or reduce the frequency of
      psychosis in schizophrenia, or reduce the severity of post-acute psychosis,
      although it is difficult to reach unambiguous conclusions about the efficacy of
      treatment in purely naturalistic or observational research. Longitudinally, on
      the basis of their psychotic activity and the disruption of functioning, the
      condition of the majority of SZ prescribed antipsychotics for multiple years
      would raise questions as to how many of them are truly in remission.

PMID- 25066793
TI  - Endothelial cells in peripheral blood film.

PMID- 25066794
TI  - Voice disorders induced by bevacizumab administration in an ovarian cancer
      patient: an underestimated and rare toxicity.

PMID- 25066795
TI  - Anaplastic large cell lymphoma presenting as a cerebellar mass.
AB  - Anaplastic large cell lymphoma (ALCL) is a T cell lymphoma occurring commonly in
      childhood and rarely in adults. Central nervous system involvement in ALCL is
      very rare and cerebellar involvement at presentation has never been described. We
      examine the case of a young adult who presented with a cerebellar mass. A 19-year
      old boy presented with signs of raised intracranial tension, which, on imaging,
      revealed a right cerebellar mass. He underwent suboccipital craniotomy and
      partial excision of the tumor. However, the histopathology was inconclusive. He
      subsequently presented with cerebellar signs and repeat imaging showed recurrence
      of the cerebellar lesion. He underwent decompression and ventriculoperitoneal
      (VP) shunting. Histopathology was suggestive of ALK (anaplastic lymphoma kinase)
      positive anaplastic large cell lymphoma. The patient was started on chemotherapy.
      However, his neurological status deteriorated, his condition worsened, and he
      expired a month later. 

PMID- 25066796
TI  - [Unusual presentation of juvenile idiopathic arthritis and autoimmune hepatitis].
AB  - The coexistence of autoimmune hepatitis and juvenile idiopathic arthritis is very
      rare. This is the case of an 18 month old female patient whose first sign of
      disease was torticollis due to an underlying atlanto-axial subluxation. Three
      months later, bilateral knee arthritis developed and she was diagnosed with
      Juvenile Idiopathic Arthritis. Throughout the disease a persistent elevation of
      liver enzymes was noted, combined with positive antinuclear antibodies and
      hypergammaglobulinemia, reaching the diagnosis of concomitant autoimmune
      hepatitis. 

PMID- 25066797
TI  - [Polyvalent meningococcal vaccines: within or outside our agenda?].
AB  - The development of tetravalent vaccines against Invasive Meningococcal Disease
      (IMD) has been driven mainly due to the increase of the prevalence and geographic
      expansion of several serogroups considered unusual, but also because of the need
      for vaccines that offer broad spectrum protection in a devastating disease such
      as IMD. These changes in serogroups considered usual (B and C) have been detected
      for both serogroup Y and W, which has led to the multivalent vaccines being used
      by a number of countries with different strategies that will be discussed in the
      article. Epidemiological data in Spain, currently do not justify its use in
      immunization schedules, but there is a potential risk for the introduction of
      virulent clones of those uncommon serogroups (Y and W), and this would lead us to
      open a discussion of their potential use, particularly in the adolescent/pre-teen
      population as a target group for intervention. 

PMID- 25066798
TI  - Editorial overview: Host-microbe interactions: fungi.

PMID- 25066799
TI  - Editorial overview: Host-microbe interactions: viruses: Viral sensing and
      activation of immunity.

PMID- 25066801
TI  - The mitochondrial-targeted antioxidant MitoQ ameliorates metabolic syndrome
      features in obesogenic diet-fed rats better than Apocynin or Allopurinol.
AB  - The prevalence of metabolic syndrome (MetS) components including obesity,
      dyslipidemia, insulin resistance (IR), and hepatic steatosis is rapidly
      increasing in wealthy societies. It is accepted that inflammation/oxidative
      stress are involved in the initiation/evolution of the MetS features. The present
      work was designed to evaluate the effects of three major cellular ROS production
      systems on obesity, glucose tolerance, and hepatic steatosis development and on
      oxidative stress onset. To do so, 40 young male Sprague-Dawley rats were divided
      into 5 groups: 1-control group, 2-high fat (HF) group (60% energy from fat), 3
      HF+ MitoQ (mitochondrial ROS scavenger), 4-HF+ Apocynin (NADPH oxidase
      inhibitor), 5-HF+ Allopurinol (xanthine oxidase inhibitor). After 8 weeks of
      these treatments, surrogate MetS, mitochondrial function, and oxidative stress
      markers were measured in blood and liver. As expected, rats that were fed the HF
      diet exhibited increased body weight, glucose intolerance, overt hepatic
      steatosis, and increased hepatic oxidative stress. The impacts of the studied ROS
      inhibitors on these aspects of the MetS were markedly different. MitoQ showed the
      most clinically relevant effects, attenuating body weight gain and glucose
      intolerance provoked by the HF diet. Both Apocynin and Allopurinol showed limited
      effects suggesting secondary roles of xanthine oxidase (XO) or NADPH oxidase
      dependent ROS production in the onset of oxidative stress-dependent obesity,
      glucose intolerance, and hepatic steatosis process. Thus, MitoQ revealed the
      central role of mitochondrial oxidative stress in the development of MetS and
      suggested that mitochondria-targeted antioxidants may be worth considering as
      potentially helpful therapies for MetS features.

PMID- 25066800
TI  - Independent stratum formation on the avian sex chromosomes reveals inter
      chromosomal gene conversion and predominance of purifying selection on the W
      chromosome.
AB  - We used a comparative approach spanning three species and 90 million years to
      study the evolutionary history of the avian sex chromosomes. Using whole
      transcriptomes, we assembled the largest cross-species dataset of W-linked coding
      content to date. Our results show that recombination suppression in large
      portions of the avian sex chromosomes has evolved independently, and that long
      term sex chromosome divergence is consistent with repeated and independent
      inversions spreading progressively to restrict recombination. In contrast, over
      short-term periods we observe heterogeneous and locus-specific divergence. We
      also uncover four instances of gene conversion between both highly diverged and
      recently evolved gametologs, suggesting a complex mosaic of recombination
      suppression across the sex chromosomes. Lastly, evidence from 16 gametologs
      reveal that the W chromosome is evolving with a significant contribution of
      purifying selection, consistent with previous findings that W-linked genes play
      an important role in encoding sex-specific fitness. 

PMID- 25066802
TI  - Drivers and risk factors for circulating African swine fever virus in Uganda,
      2012-2013.
AB  - We explored observed risk factors and drivers of infection possibly associated
      with African swine fever (ASF) epidemiology in Uganda. Representative sub
      populations of pig farms and statistics were used in a case-control model.
      Indiscriminate disposal of pig viscera and waste materials after slaughter,
      including on open refuse dumps, farm-gate buyers collecting pigs and pig products
      from within a farm, and retention of survivor pigs were plausible risk factors.
      Wire mesh-protected windows in pig houses were found to be protective against ASF
      infection. Sighting engorged ticks on pigs, the presence of a lock for each pig
      pen and/or a gate at the farm entrance were significantly associated with
      infection/non-infection; possible explanations were offered. Strict adherence to
      planned within-farm and community-based biosecurity, and avoidance of identified
      risk factors is recommended to reduce infection. Training for small-scale and
      emerging farmers should involve multidimensional and multidisciplinary approaches
      to reduce human-related risky behaviours driving infection. 

PMID- 25066803
TI  - Biofilm formation in Haemophilus parasuis: relationship with antibiotic
      resistance, serotype and genetic typing.
AB  - Biofilms are surface-associated microbial communities, which are encased in self
      synthesized extracellular environment. Biofilm formation may trigger drug
      resistance and inflammation, resulting in persistent infections. Haemophilus
      parasuis is the etiological agent of a systemic disease, Glasser's disease,
      characterized by fibrinous polyserositis, arthritis and meningitis in pigs. The
      purpose of this study was to examine the correlation between biofilm and
      antibiotic resistance among the clinical isolates of H. parasuis. In the present
      study, we tested biofilm-forming ability of 110 H. parasuis isolates from various
      farms using polystyrene microtiter plate assays. Seventy-three isolates of H.
      parasuis (66.4%) showed biofilm formation and most of them performed weak biofilm
      forming ability (38/73). All isolates were tested for antimicrobial
      susceptibility to 18 antimicrobial agents by the broth microdilution method. H.
      parasuis isolates showed very high resistance (>90%) to sulfanilamide, nalidixic
      acid, and trimethoprim. Resistance to eight antibiotics such as penicillin (41.1%
      vs 8.1%), ampicillin (31.5% vs 8.1%), amoxicillin (28.8% vs 5.4%), gentamicin
      (46.6% vs 24.3%), cefazolin (19.2% vs 2.7%), doxycycline (19.2% vs 8.1%),
      cefotaxime (11% vs 2.7%), and cefaclor (13.7% vs 5.4%) was comparatively higher
      among biofilm producers than non-biofilm producers. Pulsed-field gel
      electrophoresis (PFGE) analyses could distinguish various isolates. Our data
      indicated that H. parasuis field isolates were able to form biofilms in vitro. In
      addition, biofilm positive strains had positive correlation with resistance to
      beta-lactams antibiotics. Thus, biofilm formation may play important roles during
      H. parasuis infections. 

PMID- 25066804
TI  - Measuring the societal burden of cancer: the cost of lost productivity due to
      premature cancer-related mortality in Europe.
AB  - Every cancer-related death in someone of working age represents an economic loss
      to society. To inform priorities for cancer control, we estimated costs of lost
      productivity due to premature cancer-related mortality across Europe, for all
      cancers and by site, gender, region and country. Cancer deaths in 2008 were
      obtained from GLOBOCAN for 30 European countries across four regions. Costs were
      valued using the human capital approach. Years of productive life lost (YPLL)
      were computed by multiplying deaths between 15 and 64 years by working-life
      expectancy, then by country-, age- and gender-specific annual wages, corrected
      for workforce participation and unemployment. Lost productivity costs due to
      premature cancer-related mortality in Europe in 2008 were ?75 billion. Male costs
      (?49 billion) were almost twice female costs (?26 billion). The most costly sites
      were lung (?17 billion; 23% of total costs), breast (?7 billion; 9%) and
      colorectum (?6 billion; 8%). Stomach cancer (in Southern and Central-Eastern
      Europe) and pancreatic cancer (in Northern and Western Europe) were also among
      the most costly sites. The average lost productivity cost per cancer death was
      ?219,241. Melanoma had the highest cost per death (?312,798), followed by Hodgkin
      disease (?306,628) and brain and CNS cancer (?288,850). Premature mortality costs
      were 0.58% of 2008 European gross domestic product, highest in Central-Eastern
      Europe (0.81%) and lowest in Northern Europe (0.51%). Premature cancer-related
      mortality costs in Europe are significant. These results provide a novel
      perspective on the societal cancer burden and may be used to inform priority
      setting for cancer control. 

PMID- 25066805
TI  - Proteolipid protein cannot replace P0 protein as the major structural protein of
      peripheral nervous system myelin.
AB  - The central nervous system (CNS) of terrestrial vertebrates underwent a prominent
      molecular change when proteolipid protein (PLP) replaced P0 protein as the most
      abundant protein of CNS myelin. However, PLP did not replace P0 in peripheral
      nervous system (PNS) myelin. To investigate the possible consequences of a PLP to
      P0 shift in PNS myelin, we engineered mice to express PLP instead of P0 in PNS
      myelin (PLP-PNS mice). PLP-PNS mice had severe neurological disabilities and died
      between 3 and 6 months of age. Schwann cells in sciatic nerves from PLP-PNS mice
      sorted axons into one-to-one relationships but failed to form myelin internodes.
      Mice with equal amounts of P0 and PLP had normal PNS myelination and lifespans
      similar to wild-type (WT) mice. When PLP was overexpressed with one copy of the
      P0 gene, sciatic nerves were hypomyelinated; mice displayed motor deficits, but
      had normal lifespans. These data support the hypothesis that while PLP can co
      exist with P0 in PNS myelin, PLP cannot replace P0 as the major structural
      protein of PNS myelin.

PMID- 25066806
TI  - Personalized cost-effectiveness of boceprevir-based triple therapy for untreated
      patients with genotype 1 chronic hepatitis C.
AB  - BACKGROUND: We assessed the cost-effectiveness of boceprevir-based triple therapy
      compared to peginterferon alpha and ribavirin dual therapy in untreated patients
      with genotype 1 chronic hepatitis C; patients were discriminated according to the
      combination of baseline plus on-treatment predictors of boceprevir-based triple
      therapy. METHODS: Cost-effectiveness analysis performed according to data from
      the available published literature. The target population was composed of
      untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C,
      and these were evaluated over a lifetime horizon by Markov model. The study was
      carried out from the perspective of the Italian National Health Service. Outcomes
      included discounted costs (in euro, at 2013 value), life-years gained, quality
      adjusted life year, and incremental cost-effectiveness ratio. The robustness of
      the results was evaluated by multivariable probabilistic sensitivity analyses.
      RESULTS: According to the baseline predictors of sustained virological response
      (genotype 1b, low viral load, fibrosis F0-F3, and body mass index) and the 1Log
      drop of HCV-RNA after the dual therapy lead-in period, boceprevir was cost
      effective in different patient profiles. CONCLUSIONS: In untreated genotype 1b
      chronic hepatitis C patients, the cost-effectiveness of boceprevir-based triple
      therapy widely ranges according to different profiles of sustained virological
      response predictors, allowing optimization and personalization of triple therapy.

PMID- 25066807
TI  - Sialyltransferase ST3Gal IV deletion protects against temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) often becomes refractory, and patients with TLE show
      a high incidence of psychiatric symptoms, including anxiety and depression.
      Therefore, it is necessary to identify molecules that were previously unknown to
      contribute to epilepsy and its associated disorders. We previously found that the
      sialyltransferase ST3Gal IV is up-regulated within the neural circuits through
      which amygdala-kindling stimulation propagates epileptic seizures. In contrast,
      this study demonstrated that kindling stimulation failed to evoke epileptic
      seizures in ST3Gal IV-deficient mice. Furthermore, approximately 80% of these
      mice failed to show tonic-clonic seizures with stimulation, whereas all
      littermate wild-type mice showed tonic-clonic seizures. This indicates that the
      loss of ST3Gal IV does not cause TLE in mice. Meanwhile, ST3Gal IV-deficient mice
      exhibited decreased acclimation in the open field test, increased immobility in
      the forced swim test, enhanced freezing during delay auditory fear conditioning,
      and sleep disturbances. Thus, the loss of ST3Gal IV modulates anxiety-related
      behaviors. These findings indicate that ST3Gal IV is a key molecule in the
      mechanisms underlying anxiety - a side effect of TLE - and may therefore also be
      an effective target for treating epilepsy, acting through the same circuits.

PMID- 25066808
TI  - Clinical coaching--an innovative role to improve marginal nursing students'
      clinical practice.
AB  - In order for undergraduate nursing students to demonstrate their ability to
      achieve the required level of competency with practice they must be able to
      integrate both the clinical skills and knowledge that are pivotal to safe and
      competent nursing practice. In response to ongoing concerns about students' level
      of competency expressed by the supervising clinical staff, one School of Nursing
      and Midwifery created a Clinical Coach (CC) role. The purpose of this paper is to
      present the data collected including outcomes achieved and the coaching
      strategies used when a CC role was implemented to support and develop nursing
      practice for the marginal performer or 'at risk' student. A literature review of
      the application of coaching to nursing, a detailed analysis and discussion of the
      outcomes identified from auditing of collected data and the specific coaching
      strategies that resulted in successful outcomes for students is presented. This
      model of Clinical Coaching for nursing students could readily be adopted by other
      Schools of Nursing and Midwifery. This account of the regime of coaching
      practices may also offer a transferable, adaptable and flexible approach for
      other health professions who require their undergraduate students to complete
      clinical placements in preparation for professional practice. 

PMID- 25066809
TI  - Chinese nurses' relief experiences following two earthquakes: implications for
      disaster education and policy development.
AB  - Disasters require well trained nurses but disaster nursing education is very
      limited in China and evidence is urgently required for future planning and
      implementation of specialized disaster education. This describes the themes
      arising from narratives of Chinese registered nurses who worked in disaster
      relief after two major earthquakes. In-depth interviews were held with 12
      registered nurses from Hubei Province. Riessman's narrative inquiry method was
      used to develop individual stories and themes, and socio-cultural theory informed
      this study. Five themes emerged: unbeatable challenges; qualities of a disaster
      nurse; mental health and trauma; poor disaster planning and co-ordination; and
      urgently needed disaster education. Participants were challenged by rudimentary
      living conditions, a lack of medical equipment, earthquake aftershocks, and
      cultural differences in the people they cared for. Participants placed importance
      on the development of teamwork abilities, critical thinking skills, management
      abilities of nurses in disasters, and the urgency to build a better disaster
      response system in China in which professional nurses could more actively
      contribute their skills and knowledge. Our findings concur with previous research
      and emphasize the urgency for health leaders across China to develop and
      implement disaster nursing education policies and programs. 

PMID- 25066810
TI  - A moire deflectometer for antimatter.
AB  - The precise measurement of forces is one way to obtain deep insight into the
      fundamental interactions present in nature. In the context of neutral antimatter,
      the gravitational interaction is of high interest, potentially revealing new
      forces that violate the weak equivalence principle. Here we report on a
      successful extension of a tool from atom optics--the moire deflectometer--for a
      measurement of the acceleration of slow antiprotons. The setup consists of two
      identical transmission gratings and a spatially resolving emulsion detector for
      antiproton annihilations. Absolute referencing of the observed antimatter pattern
      with a photon pattern experiencing no deflection allows the direct inference of
      forces present. The concept is also straightforwardly applicable to antihydrogen
      measurements as pursued by the AEgIS collaboration. The combination of these very
      different techniques from high energy and atomic physics opens a very promising
      route to the direct detection of the gravitational acceleration of neutral
      antimatter.

PMID- 25066811
TI  - Genetic and clinical analysis of ABCA4-associated disease in African American
      patients.
AB  - Autosomal recessive Stargardt disease (STGD1) is caused by hundreds of mutations
      in the ABCA4 gene, which are often specific to racial and ethnic groups. Here, we
      investigated the ABCA4 variation and their phenotypic expression in a cohort of
      44 patients of African American descent, a previously under-characterized racial
      group. Patients were screened for mutations in ABCA4 by next-generation
      sequencing and array-comparative genomic hybridization (aCGH), followed by
      analyses for pathogenicity by in silico programs. Thorough ophthalmic examination
      was performed on all patients. At least two (expected) disease-causing alleles in
      the ABCA4 gene were identified in 27 (61.4%) patients, one allele in 11 (25%)
      patients, and no ABCA4 mutations were found in six (13.6%) patients. Altogether,
      39 different disease-causing ABCA4 variants, including seven new, were identified
      on 65 (74%) chromosomes, most of which were unique for this racial group. The
      most frequent ABCA4 mutation in this cohort was c.6320G>A (p.(R2107H)),
      representing 19.3% of all disease-associated alleles. No large copy number
      variants were identified in any patient. Most patients reported later onset of
      symptoms. In summary, the ABCA4 mutation spectrum in patients of West African
      descent differs significantly from that in patients of European descent,
      resulting in a later onset and "milder" disease. 

PMID- 25066812
TI  - Non-myeloablative conditioning with busulfan before hematopoietic stem cell
      transplantation leads to phenotypic correction of murine Bernard-Soulier
      syndrome.
AB  - BACKGROUND: Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder
      characterized by macrothrombocytopenia. Platelet transfusion is used for the
      management of bleeding, but repeated transfusion often results in
      alloimmunization. We have recently shown phenotypic correction of murine BSS
      (GPIbalpha(null) ) using lethal radiation conditioning followed by hematopoietic
      lentivirus-mediated gene transfer. OBJECTIVES: For application of gene therapy to
      treatment of human patients, it is important to minimize treatment-related side
      effects. The objective of this study is to model a clinically relevant non
      myeloablative hematopoietic stem cell (HSC) transplantation strategy. METHODS:
      Using transplantation of bone marrow (BM) HSCs from transgenic mice that express
      hGPIbalpha (hGPIbalpha(tg+/+) ), we sought to (i) determine the percentage of
      hGPIbalpha(tg+/+) HSCs required for therapeutic benefit, (ii) evaluate the
      efficacy of non-myeloablative conditioning using busulfan, and (iii) test the
      ability of anti-thymocyte globulin (ATG) to prevent/reduce undesirable immune
      responses. RESULTS: Transplantation of 10-20% hGPIbalpha(tg+/+) BM HSCs mixed
      with GPIbalpha(null) BM HSCs into irradiated GPIbalpha(null) mice was sufficient
      to correct bleeding time (n = 5). Transplantation of hGPIbalpha(tg+/+) BM HSCs
      into busulfan-conditioned GPIbalpha(null) mice corrected bleeding time in 21 of
      27 recipients. Antibody response to hGPIbalpha and immune-mediated
      thrombocytopenia was documented in eight of 27 recipients, suggesting
      immunogenicity of hGPIbalpha in busulfan-conditioned GPIbalpha(null) mice.
      However, these antibodies disappeared without treatment within 30 weeks after
      transplantation. A combination of busulfan plus ATG conditioning successfully
      prevented antibody development and significantly increased therapeutic
      engraftment. CONCLUSION: A conditioning regimen of busulfan in combination with
      ATG could potentially be used in non-myeloablative autologous gene therapy in
      human BSS.

PMID- 25066813
TI  - Meropenem-induced myoclonus: a case report.

PMID- 25066814
TI  - The role of azoles in the management of azole-resistant aspergillosis: from the
      bench to the bedside.
AB  - Azole resistance is an emerging problem in Aspergillus fumigatus and is
      associated with a high probability of treatment failure. An azole resistance
      mechanism typically decreases the activity of multiple azole compounds, depending
      on the mutation. As alternative treatment options are limited and in some
      isolates the minimum inhibitory concentration (MIC) increases by only a few two
      fold dilutions steps, we investigated if voriconazole and posaconazole have a
      role in treating azole-resistant Aspergillus disease. The relation between
      resistance genotype and phenotype, pharmacokinetic and pharmacodynamic
      properties, and (pre)clinical treatment efficacy were reviewed. The results were
      used to estimate the exposure needed to achieve the pharmacodynamic target for
      each MIC. For posaconazole adequate exposure can be achieved only for wild type
      isolates as dose escalation does not allow PD target attainment. However, the new
      intravenous formulation might result in sufficient exposure to treat isolates
      with a MIC of 0.5 mg/L. For voriconazole our analysis indicated that the exposure
      needed to treat infection due to isolates with a MIC of 2 mg/L is feasible and
      maybe isolates with a MIC of 4 mg/L. However, extreme caution and strict
      monitoring of drug levels would be required, as the probability of toxicity will
      also increase.

PMID- 25066816
TI  - Rapid, photocatalytic, and deep debromination of polybrominated diphenyl ethers
      on Pd-TiO2: intermediates and pathways.
AB  - Titanium dioxide with surface-loaded palladium (Pd-TiO2) was able to easily
      remove all ten bromine atoms from decabromodiphenyl ether (BDE209) within 1 h
      under the irradiation of sunlight or an artificial light source. By contrast,
      fewer than three bromine atoms were eliminated on the pristine TiO2 even with
      prolonged irradiation (5 h). During the photocatalytic debromination, moreover,
      the formed BDE intermediates exhibited a significant difference between the Pd
      TiO2 and pristine TiO2 systems, and much less position selectivity for the
      debromination on Pd-TiO2 was observed than that on the pristine TiO2 surface. For
      another polybrominated diphenyl ether (BDE15), pristine TiO2 was incapable of its
      photocatalytic reduction, whereas the loading of Pd enabled its debromination to
      diphenyl ether within 20 min. In addition, an evident induction period appeared
      in the photocatalytic debromination of BDE15 on Pd-TiO2. The experiments imply
      that the Pd-cocatalyzed effect changes significantly the photocatalytic reductive
      debromination pathways.

PMID- 25066815
TI  - Serum neutrophil gelatinase-associated lipocalin and recovery of kidney graft
      function after transplantation.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a marker for
      acute kidney injury. We studied whether serum NGAL predicts delayed graft
      function (DGF) and recovery of kidney function after transplantation. METHODS:
      Serum NGAL was analyzed using commercial ELISA and point-of-care (POC)
      (Triage(r), Biosite) methods. Serum samples were collected from 176 consecutive,
      deceased-donor kidney recipients just before transplant surgery and on day 1 and
      14 after transplantation. The first 132 samples were analyzed with both methods
      and the remaining samples with the POC method. RESULTS: The correlation between
      the ELISA and POC methods was 0.89, p < 0.0001 and hence the POC method was used
      for the remaining analyses. DGF was seen in 66/176 patients. Day 1 sNGAL was
      significantly higher in DGF (588 ng/ml, SD 189.6) compared to early graft
      function (355 ng/ml, SD 166.2, p < 0.0001) and this difference persisted on day
      14. Day 1 sNGAL predicted DGF with an area under the curve (AUC) of 0.853 (CI
      0.792-0.914, p < 0.0001). At the optimal cutoff level of 423 ng/ml the
      sensitivity was 87% and the specificity 77%. In a multivariate analysis, day 1
      sNGAL emerged as an independent predictor of DGF. The sNGAL also predicted DGF
      lasting longer than 14 days with an AUC of 0.825 (CI 0.751-0.899, p < 0.0001). At
      the optimal cutoff level of 486 ng/ml, the sensitivity was 80% and specificity
      75%. CONCLUSION: Serum NGAL predicts clinically significant DGF and is useful in
      the care of kidney transplant recipients.

PMID- 25066817
TI  - Repeated simulation-based training for performing general anesthesia for
      emergency cesarean delivery: long-term retention and recurring mistakes.
AB  - BACKGROUND: The percentage of women undergoing cesarean delivery under general
      anesthesia has significantly decreased, which limits training opportunities for
      its safe administration. The purpose of this study was to evaluate how effective
      simulation-based training was in the learning and long-term retention of skills
      to perform general anesthesia for an emergent cesarean delivery. METHODS: During
      an eight-week obstetric anesthesia rotation, 24 residents attended lectures and
      simulation-based training to perform general anesthesia for emergent cesarean
      delivery. Performance assessments using a validated weighted scaling system were
      made during the first (pre-test) and fifth weeks (post-test) of training, and
      eight months later (post-retention test). Resident's competency level (weighted
      score) and errors were assessed at each testing session. Six obstetric anesthesia
      attending physicians, unfamiliar with the simulation scenario, generated a mean
      attendings' performance score. The results were compared. RESULTS: At one week of
      training, residents' performance was significantly below mean attendings'
      performance score (pre-test: 135+/-22 vs. 159+/-11, P=0.013). At five weeks,
      residents' performance was similar to mean attendings' performance score (post
      test: 159+/-21) and remained at that level at eight months (post-retention test:
      164+/-16). Of the important obstetric-specific tasks, left uterine displacement
      was missed by 46% of residents at eight months. CONCLUSION: Following lectures
      and simulation-enhanced training, anesthesia residents reached and retained for
      up to eight months a competency level in a simulator comparable to that of
      obstetric anesthesia attending physicians. Errors in performance and missed tasks
      may be used to improve residency training and continuing medical education.

PMID- 25066818
TI  - Trans-oesophageal Doppler-guided fluid management in massive obstetric
      haemorrhage.

PMID- 25066819
TI  - Anesthetic management of maternal Mirror syndrome.
AB  - Mirror syndrome (Ballantyne syndrome, triple edema, maternal hydrops,
      pseudotoxemia) is a rarely diagnosed condition associated with pregnancy that can
      be life-threatening for both the mother and fetus. There is limited literature on
      its pathogenesis and anesthetic management, making prevention and treatment
      complex. The duration of pregnancy and severity of maternal or fetal presentation
      often determines outcome. We describe the anesthetic considerations of a morbidly
      obese parturient with Mirror syndrome. 

PMID- 25066821
TI  - Regarding "reverse total shoulder arthroplasty for acute proximal humeral
      fracture: comparison to open reduction-internal fixation and hemiarthroplasty".

PMID- 25066820
TI  - High prevalence of chronic kidney disease in Finnish patients with type 2
      diabetes treated in primary care.
AB  - OBJECTIVE: To examine the prevalence of chronic kidney disease (CKD) and related
      cardiovascular morbidity in a cross-sectional population in patients with type 2
      diabetes (T2D) treated in a primary care setting in Finland. RESEARCH DESIGN AND
      METHODS: Data were collected and recorded from 42 primary care centres, which
      recruited 629 patients diagnosed with type 2 diabetes (T2D) to this non
      interventional study. Data including patient characteristics, kidney function and
      albuminuria, blood pressure, HbA1c, lipid and lipoprotein levels, and diabetes
      duration as well as current medication was collected in each patient. RESULTS: In
      the final study population of 625 patients, the mean age was 67 years (range 29
      92 years), BMI 32.8 kg/m(2) (95% CI 32-33), blood pressure 142/80 mmHg (140
      143/80-81) and HbA1c 7.1% (7.0-7.2) (53.8 mmol/mol, 53-55) and the median
      duration of diabetes was 9.2 years ranging from newly diagnosed to 43 years.
      History of dyslipidemia had in 73.3% of patients, 27.8% had cardiovascular
      disease and 82.7% had hypertension. The primary endpoint, prevalence of CKD of
      any grade (1-5) or albuminuria, was 68.6%. Regarding declined renal function,
      16.2% of patients had an estimated glomerular filtration rate (eGFR) <60
      ml/min/1.72 m(2), classifying as CKD 3-5. Only one patient was within CKD5.
      Regarding renal damage, albuminuria was present in 24.3% of patients, with
      microalbuminuria in 17.1% and macroalbuminuria in 7.2%, respectively. Combining
      the patients with CKD 3-5 and/or the presence of albuminuria, 34.7% seemed to
      suffer from significant CKD. The proportion of patients with albuminuria
      increased with a decrease in glomerular filtration rate. Historically, diabetic
      nephropathy had been diagnosed in 24.3% of the patients. CONCLUSIONS: Nearly 70%
      of patients with T2D treated in primary care in Finland have some sign of CKD and
      nearly half of all T2D patients have a significant CKD. However, only half of the
      latter had it diagnosed and documented in their patient charts, thus highlighting
      the importance of performing routine screening of nephropathy by measuring both
      albuminuria and eGFR in patients with T2D. Prevention of this complication with
      active therapy for risk factors, such as hypertension and dyslipidemia is
      warranted.

PMID- 25066822
TI  - Author reply: reverse total shoulder for acute proximal humeral fracture:
      comparison to open reduction-internal fixation and hemiarthroplasty.

PMID- 25066823
TI  - Optimizing potentials for a liquid mixture: a new force field for a tert-butanol
      and water solution.
AB  - A technology for optimization of potential parameters from condensed-phase
      simulations (POP) is discussed and illustrated. It is based on direct
      calculations of the derivatives of macroscopic observables with respect to the
      potential parameters. The derivatives are used in a local minimization scheme,
      comparing simulated and experimental data. In particular, we show that the Newton
      trust region protocol allows for more accurate and robust optimization. We apply
      the newly developed technology to study the liquid mixture of tert-butanol and
      water. We are able to obtain, after four iterations, the correct phase behavior
      and accurately predict the value of the Kirkwood Buff (KB) integrals. We further
      illustrate that a potential that is determined solely by KB information, or the
      pair correlation function, is not necessarily unique. 

PMID- 25066824
TI  - Hyphomonas atlanticus sp. nov., isolated from the Atlantic Ocean and emended
      description of the genus Hyphomonas.
AB  - A taxonomic study was carried out on strains 22II1-22F38(T) and 22II-S13e, which
      were isolated from sea water and sediment from the Atlantic Ocean, respectively.
      The two strains were Gram-negative, oxidase and catalase positive, oval to pear
      shaped, and motile by a single polar flagellum. Phylogenetic analysis based on
      16S rRNA gene sequences indicated that both strains belonged to the genus
      Hyphomonas, with highest sequence similarity (98.2%) to the type strains H.
      jannaschiana DSM 5153(T) and H. johnsonii ATCC 43964(T). The genomic ANIm values
      and DNA-DNA hybridization estimate values between strain 22II1-22F38(T) and seven
      type strains ranged from 82.84% to 84.10% and from 18.0% to 19.1%, respectively.
      Isolate 22II1-22F38(T) had a G+C content of 58.3% and used Q-11 as the
      predominant respiratory quinone. The combined phenotypic and genotypic data
      showed that both strains represented a novel species of the genus Hyphomonas, for
      which the name Hyphomonas atlanticus sp. nov. is proposed, with the type strain
      being 22II1-22F38(T) (=LMG 27916(T)=MCCC 1A09418(T)). In addition, we conclude
      that Hyphomonas hirschiana is a later synonym of Hyphomonas neptunium.

PMID- 25066825
TI  - Archaeal and bacterial diversity in five different hydrothermal ponds in the
      Copahue region in Argentina.
AB  - Copahue is an acidic geothermal volcanic region in the northwest corner of
      Neuquen Province, Argentina. In the area, there are various ponds, pools and hot
      springs with different temperatures, pH values and levels of anthropogenic
      influence. In this study, the prokaryotic biodiversity of five representative
      ponds was studied by using two complementary molecular ecology techniques:
      phylogenetic analysis of 16S rRNA bacterial and archaeal genes and FISH (or CARD
      FISH) for quantitative estimation of biodiversity. The results, supported by
      multivariate statistical analysis, showed that the biodiversity in Copahue ponds
      seemed to be determined by temperature. High temperature ponds were dominated by
      archaea, mainly apparently novel representatives from the orders Sulfolobales and
      Thermoplasmatales that had no close cultivated relatives. By contrast, moderate
      temperature ponds were colonised by well-characterised sulphur-oxidising bacteria
      related to acidic environments, such as other geothermal sites or acid mine
      drainage, and archaea were absent. By combining the biodiversity results from
      this study and the reported physicochemical features of Copahue, a preliminary
      model of the possible biogeochemical interaction was outlined for moderate and
      high temperature ponds. 

PMID- 25066826
TI  - Molecular cloning, relative expression, and structural analysis of pattern
      recognition molecule beta-glucan binding protein from mangrove crab Episesarma
      tetragonum.
AB  - A full-length cDNA of a beta-glucan binding protein (beta-GBP) gene was
      identified from the mangrove crab Episesarma tetragonum. The open reading frame
      of the E. tetragonum beta-GBP (Epte beta-GBP) is 1,167 bp long, encoding a
      polypeptide of 389 amino acids. The deduced amino acid sequence of Epte beta-GBP
      gene has conserved a potential recognition motif for beta-1,3 linkages of
      polysaccharides and putative RGD (Arg-Gly-Asp) cell adhesion sites. Phylogenetic
      analysis of the Epte beta-GBP gene showed the similarity with beta-GBPs of other
      crustaceans and arthropods. Quantitative RT-PCR results showed the upregulation
      of Epte beta-GBP gene expression in E. tetragonum hemocytes following a 12-H
      challenge in response to beta-glucan (beta-G). Epte beta-GBP was involved in the
      regulation and activation of the prophenoloxidase cascade. A three-dimensional
      structure of active Epte beta-GBP was modeled by homology modeling and refined
      with molecular dynamics simulations. A structural aspect of the protein is
      discussed based on experimental and theoretical results obtained.

PMID- 25066827
TI  - Are we really mapping psychosis risk? Neuroanatomical signature of affective
      disorders in subjects at ultra high risk.
AB  - BACKGROUND: The majority of people at ultra high risk (UHR) of psychosis also
      present with co-morbid affective disorders such as depression or anxiety. The
      neuroanatomical and clinical impact of UHR co-morbidity is unknown. METHOD: We
      investigated group differences in grey matter volume using baseline magnetic
      resonance images from 121 participants in four groups: UHR with depressive or
      anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls.
      The impact of grey matter volume on baseline and longitudinal clinical/functional
      data was assessed with regression analyses. RESULTS: The UHR-co-morbidity group
      had lower grey matter volume in the anterior cingulate cortex than the UHR-alone
      group, with an intermediate effect between controls and patients with major
      depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate
      volume was negatively correlated with baseline suicidality/self-harm and
      obsessive-compulsive disorder symptoms. CONCLUSIONS: Co-morbid depression and
      anxiety disorders contributed distinctive grey matter volume reductions of the
      anterior cingulate cortex in people at UHR of psychosis. These volumetric
      deficits were correlated with baseline measures of depression and anxiety,
      suggesting that co-morbid depressive and anxiety diagnoses should be carefully
      considered in future clinical and imaging studies of the psychosis high-risk
      state.

PMID- 25066828
TI  - Therapeutic effect of human adipose-derived stromal cells cluster in rat hind
      limb ischemia.
AB  - We investigated whether transplantation of three-dimensional cell masses (3DCM)
      of human adipose-derived stromal cells (hASCs) cultured on a basic fibroblast
      growth factor-immobilized substrate improved hind limb functional recovery by
      stimulating angiogenesis in an immune-competent rat ischemic limb model. In vitro
      experiments confirmed that cells within 3DCMs differentiate toward the
      endothelial lineage one day after culture in normal medium. The therapeutic
      effect of 3DCMs was evaluated by transplanting hASCs, phosphate-buffered saline
      alone, and the 3DCM into rat ischemic hind limbs. Blood flow was enhanced in the
      ischemic hind limb in the 3DCM-injected group compared with the other groups. The
      ratio of human nuclear antigen (HNA) and hVEGF-positive cells was significantly
      higher in the 3DCM-injected group compared to hASC-injected group. Human VEGF was
      observed in most HNA-positive cells. Many hCD31 and hSMA-positive cells were
      observed in vessel-like structures in the 3DCM-injected group. The 3DCM
      transplantation improved cell retention and angiogenic effects compared with ASC
      transplantation. These findings suggest that transplantation of 3DCMs may be an
      effective stem cell therapy for hind limb ischemia.

PMID- 25066829
TI  - Effects of liposome-encapsulated hemoglobin on learning ability in tokai high
      avoider rat after total brain ischemia and reperfusion.
AB  - Liposome-encapsulated hemoglobin with low O2 -affinity (l-LEH) was shown to be
      protective in focal brain ischemia and reperfusion (I/R) in rats and primates. We
      tested l-LEH in the transient whole brain ischemia in the Tokai high-avoider rat
      (THA), which has been selected, mated, and bred over 77 generations for a high
      and consistent learning ability determined by the Sidman avoidance test (SAT).
      Young/naive (before SAT) and adult/parent (after SAT) THA rats underwent acute
      and complete four-vessel occlusion in the chest for 3 or 5 min, administration of
      2 mL/kg of l-LEH, saline, or homologous washed red blood cells (RBCs),
      reperfusion, and resuscitation. One week later, all rats underwent SAT, open
      field behavioral observation, Morris water maze tests, and morphological study.
      Whereas young/naive rats treated with l-LEH retained a rapid and consistent
      learning curve as in nonischemic controls, THA rats treated with RBCs or saline
      had retarded learning response on SAT as well as reduced cellularity in the
      amygdala. Adult/parent rats with established memory on SAT maintained perfect
      achievement even after I/R. In contrast, l-LEH-treated rats showed no better
      performance on Morris water maze (function) or cellularity of the CA1 sector of
      the hippocampus (morphology) compared with the rats treated with RBCs. Although
      task performance on SAT and Morris water maze appeared antithetical,
      morphological observations corresponded to the respective functions, suggesting
      that l-LEH was protective only for the amygdala on SAT tasks but not for the CA1
      sector of the hippocampus on spatial orientation as in our previous studies on
      focal brain I/R, where the cortex was preserved better than basal ganglia. 

PMID- 25066830
TI  - Shining the light on Sunshine: a systematic review of the influence of sun
      exposure on type 2 diabetes mellitus-related outcomes.
AB  - Prospective observational studies uniformly link vitamin D deficiency with the
      incidence of type 2 diabetes mellitus (T2DM), yet trials supplementing
      participants at risk of T2DM with vitamin D to reduce progression to T2DM have
      yielded inconsistent results. Inconsistencies between supplementation trials may
      be due to insufficient dosing or small sample sizes. Observational studies may
      also have reported spurious associations due to uncontrolled confounding by
      lifestyle or genetic factors. Alternatively, observational and intervention
      studies may not be entirely comparable. Observational studies show an association
      between higher vitamin D status, which is predominantly derived from sun
      exposure, and decreased incidence of T2DM. Trials intervene with vitamin D
      supplementation, and therefore may be missing alternate causes of the effect of
      sun exposure, as seen in observational studies. We propose that sun exposure may
      be the driving force behind the associations seen in observational studies; sun
      exposure may have additional benefits beyond increasing serum 25-hydroxyvitamin D
      (25OHD) levels. We performed an electronic literature search to identify articles
      that examined associations between sun exposure and T2DM and/or glucose
      metabolism. A best evidence synthesis was then conducted using outcomes from
      analyses deemed to have high methodological quality. Ten eligible full-text
      articles were identified, yielding 19 T2DM-related outcomes. The best evidence
      analysis considered 11 outcomes which were grouped into six outcome types: T2DM,
      fasting glucose, glucose tolerance, fasting insulin, insulin secretion and
      insulin sensitivity. There was moderate evidence to support a role of
      recreational sun exposure in reducing odds of T2DM incidence. High-level evidence
      was lacking; evidence presented for other outcomes was of low or insufficient
      level. This review highlights significant gaps in research pertaining to sun
      exposure and T2DM-related outcomes. Further research is encouraged as we aim to
      identify novel preventative strategies for T2DM. 

PMID- 25066831
TI  - The effects of water exposure on biophysical properties of normal skin.
AB  - BACKGROUND: Water exposure is an influential factor in some common dermatoses. It
      has also been shown that water has an effect on barrier function and biophysical
      properties of skin. The aim of this study was to evaluate the effect of water
      immersion on biophysical properties of normal skin. PARTICIPANTS & METHODS:
      Twenty healthy volunteers participated in this study. The volar aspect of
      volunteer's forearm was immersed in tap water for 30 min a day for five
      consecutive days. Biophysical skin parameters including TEWL, skin pH,
      capacitance, erythema and sebum content were measured using specific probes
      before and after the exposure and compared with unexposed other forearm as
      control. RESULTS: TEWL and pH of the exposed forearm increased significantly
      after 5 days of consecutive daily exposure to water. CONCLUSION: Water exposure
      increases the TEWL and pH of normal skin. Future studies evaluating the
      durability of the increased TEWL through monitoring the time course of events
      following skin immersion in water and susceptibility of skin to chemical
      irritants are required.

PMID- 25066832
TI  - Is non-cavitated proximal lesion sealing an effective method for caries control
      in primary and permanent teeth? A systematic review and meta-analysis.
AB  - OBJECTIVES: The aim of this study was to perform a systematic review and meta
      analysis on the effectiveness of sealing non-cavitated proximal caries lesions in
      primary and permanent teeth. DATA: Only controlled clinical trials and randomized
      controlled clinical trials that evaluated the effectiveness of sealing on non
      cavitated proximal caries with a minimum follow-up of 12 months were included in
      the study. The primary outcome should be arrestment/progression of proximal
      caries evaluated by bitewing radiographs. A risk of bias evaluation based on the
      Cochrane Collaboration common scheme for bias was carried out for each study. The
      meta-analysis was performed on the studies considered low risk of bias and with
      pair-wise visual reading results through RevMan software. SOURCES: A
      comprehensive search was performed in the Systematic Electronic Databases:
      Pubmed, Cochrane Library, Scopus, IBI Web of Science, Lilacs, SIGLE, and on
      website Clinical trials.gov, through until June 2013. STUDY SELECTION: From 967
      studies identified, 10 articles and 3 studies with partial results were assessed
      for eligibility. However three articles were excluded and our final sample
      included 10 studies. According to the risk of bias evaluation, six studies were
      considered "high" risk of bias, and four "low" risk of bias. The forest plot of
      the meta-analysis showed low heterogeneity (I(2)=29%) and a favourable outcome
      for the Infiltrant. The chance of caries progression when this technique was used
      was significantly lower (p=0.002) compared with Placebo. CONCLUSION: Our results
      suggest that the technique of sealing non-cavitated proximal caries seems to be
      effective in controlling proximal caries in the short and medium term. Further
      long-term randomized clinical trials are still necessary to increase this
      evidence. CLINICAL SIGNIFICANCE: Contemporary dentistry is focused in minimally
      invasive approaches that prevent the destruction of sound dental tissues next to
      carious lesions. This paper searches for evidence of the efficacy of
      sealing/infiltrating non-cavitated proximal caries in arresting caries
      progression both in permanent and primary teeth.

PMID- 25066833
TI  - Triple role of phenylselenonyl group enabled a one-pot synthesis of 1,3-oxazinan
      2-ones from alpha-isocyanoacetates, phenyl vinyl selenones, and water.
AB  - Reaction of alpha-substituted alpha-isocyanoacetates with phenyl vinyl selenones
      in the presence of a catalytic amount of base (DBU or Et3N, 0.05-0.1 equiv)
      followed by addition of p-toluenesulfonic acid (PTSA, 0.1-0.2 equiv) afforded
      4,4,5-trisubstituted 1,3-oxazinan-2-ones in good to excellent yields.
      Enantiomerically enriched heterocycles can also be prepared using a Cinchona
      alkaloid-derived bifunctional organocatalyst for the Michael addition step. The
      phenylselenonyl group served as an activator for the Michael addition, a leaving
      group and a latent oxidant in this integrated reaction sequence. 

PMID- 25066834
TI  - Returning to work following curative chemotherapy: a qualitative study of return
      to work barriers and preferences for intervention.
AB  - PURPOSE: This study aimed to explore barriers to return to work (RTW) and
      preferences for intervention and support for cancer patients treated with
      curative intent from the perspectives of cancer survivors and oncology health
      professionals. METHODS: Participants attended a focus group (N = 24) or an
      individual interview (N = 14). A topic guide and a semi-structured recorded
      interview format were used to gather data, which were later transcribed and
      analysed for global themes and subthemes. RESULTS: With regard to barriers, the
      global theme 'work capacity' captured an array of barriers encompassing financial
      pressure, preparedness for work, lack of confidence as well as other key
      physical, practical and psychosocial barriers. Participants expressed a
      preference for RTW models that focus on objective and structured assessment
      whilst allowing for flexibility to address individual needs. CONCLUSIONS: Cancer
      survivors perceive multiple barriers when attempting to RTW. These barriers were
      perceived to impact upon work capacity, where 'capacity' was defined broadly to
      include practical, physical and psychosocial concerns. RTW is an important
      concern for cancer survivors and structured RTW interventions should be
      incorporated into the care of cancer survivors.

PMID- 25066835
TI  - Nano-silicon dioxide mitigates the adverse effects of salt stress on Cucurbita
      pepo L.
AB  - Research into nanotechnology, an emerging science, has advanced in almost all
      fields of technology. The aim of the present study was to evaluate the role of
      nano-silicon dioxide (nano-SiO2 ) in plant resistance to salt stress through
      improvement of the antioxidant system of squash (Cucurbita pepo L. cv. white bush
      marrow). Seeds treated with NaCl showed reduced germination percentage, vigor,
      length, and fresh and dry weights of the roots and shoots. However, nano-SiO2
      improved seed germination and growth characteristics by reducing malondialdehyde
      and hydrogen peroxide levels as well as electrolyte leakage. In addition,
      application of nano-SiO2 reduced chlorophyll degradation and enhanced the net
      photosynthetic rate (Pn ), stomatal conductance (gs ), transpiration rate, and
      water use efficiency. The increase in plant germination and growth
      characteristics through application of nano-SiO2 might reflect a reduction in
      oxidative damage as a result of the expression of antioxidant enzymes, such as
      catalase, peroxidase, superoxide dismutase, glutathione reductase, and ascorbate
      peroxidase. These results indicate that nano-SiO2 may improve defense mechanisms
      of plants against salt stress toxicity by augmenting the Pn , gs , transpiration
      rate, water use efficiency, total chlorophyll, proline, and carbonic anhydrase
      activity in the leaves of plants.

PMID- 25066836
TI  - Is it possible to identify patients with inflammatory bowel disease who are at
      risk for cytomegalovirus infection?

PMID- 25066837
TI  - Levels of drug and antidrug antibodies are associated with outcome of
      interventions after loss of response to infliximab or adalimumab.
AB  - BACKGROUND & AIMS: There is controversy about whether levels of anti-tumor
      necrosis factor (TNF) and antidrug antibodies (ADAs) are accurate determinants of
      loss of response to therapy. We analyzed the association between trough levels of
      anti-TNF agents or ADAs and outcomes of interventions for patients with loss of
      response to infliximab or adalimumab. METHODS: We performed a retrospective study
      of pediatric and adult patients with inflammatory bowel disease and suspected
      loss of response to anti-TNF agents treated at medical centers throughout Israel
      from October 2009 through February 2013. We examined the correlation between
      outcomes of different interventions and trough levels of drug or ADAs during loss
      of response. An additional subanalysis was performed including only patients with
      a definite inflammatory loss of response (clinical worsening associated with
      increased levels of C-reactive protein or fecal calprotectin, or detection of
      inflammation by endoscopy, fistula discharge, or imaging studies). RESULTS: Among
      247 patients (42 with ulcerative colitis), there were 330 loss-of-response events
      (188 to infliximab and 142 to adalimumab). Trough levels of adalimumab greater
      than 4.5 mcg/mL and infliximab greater than 3.8 mcg/mL identified patients who
      failed to respond to an increase in drug dosage or a switch to another anti-TNF
      agent with 90% specificity; these were set as adequate trough levels. Adequate
      trough levels identified patients who responded to expectant management or out-of
      class interventions with more than 75% specificity. Levels of antibodies against
      adalimumab >4 microgram per mL equivalent (mcg/mL-eq) or antibodies against
      infliximab >9 mcg/mL-eq identified patients who did not respond to an increased
      drug dosage with 90% specificity. Patients with high titers of ADAs had longer
      durations of response when anti-TNF agents were switched than when dosage was
      increased (P = .03; log-rank test), although dosage increases were more effective
      for patients with no or low titers of ADAs (P = .02). An analysis of definite
      inflammatory loss-of-response events (n = 244) produced similar results; patients
      with adequate trough levels had a longer duration of response when they switched
      to a different class of agent than when anti-TNF was optimized by either a dosage
      increase or by a switch within the anti-TNF class (P = .002; log-rank test).
      CONCLUSIONS: The results of this retrospective analysis suggest that trough
      levels of drug or ADAs may guide therapeutic decisions for more than two-thirds
      of inflammatory bowel disease patients with either clinically suspected or
      definite inflammatory loss of response to therapy.

PMID- 25066838
TI  - Quantitative analysis of high-resolution microendoscopic images for diagnosis of
      esophageal squamous cell carcinoma.
AB  - BACKGROUND & AIMS: High-resolution microendoscopy is an optical imaging technique
      with the potential to improve the accuracy of endoscopic screening for esophageal
      squamous neoplasia. Although these microscopic images can be interpreted readily
      by trained personnel, quantitative image analysis software could facilitate the
      use of this technology in low-resource settings. In this study, we developed and
      evaluated quantitative image analysis criteria for the evaluation of neoplastic
      and non-neoplastic squamous esophageal mucosa. METHODS: We performed an image
      analysis of 177 patients undergoing standard upper endoscopy for screening or
      surveillance of esophageal squamous neoplasia, using high-resolution
      microendoscopy, at 2 hospitals in China and at 1 hospital in the United States
      from May 2010 to October 2012. Biopsy specimens were collected from imaged sites
      (n = 375), and a consensus diagnosis was provided by 2 expert gastrointestinal
      pathologists and used as the standard. RESULTS: Quantitative information from the
      high-resolution images was used to develop an algorithm to identify high-grade
      squamous dysplasia or invasive squamous cell cancer, based on histopathology
      findings. Optimal performance was obtained using the mean nuclear area as the
      basis for classification, resulting in sensitivities and specificities of 93% and
      92% in the training set, 87% and 97% in the test set, and 84% and 95% in an
      independent validation set, respectively. CONCLUSIONS: High-resolution
      microendoscopy with quantitative image analysis can aid in the identification of
      esophageal squamous neoplasia. Use of software-based image guides may overcome
      issues of training and expertise in low-resource settings, allowing for
      widespread use of these optical biopsy technologies.

PMID- 25066839
TI  - Histologic healing in inflammatory bowel disease clinical practice: a reliable
      target?

PMID- 25066840
TI  - Spleen stiffness as a screening strategy for esophageal varices: still not the
      answer.

PMID- 25066841
TI  - Withdrawal of immunomodulators after co-treatment does not reduce trough level of
      infliximab in patients with Crohn's disease.
AB  - BACKGROUND & AIMS: The addition of immunomodulators increases the efficacy of
      maintenance therapy with infliximab for up to 1 year in patients with Crohn's
      disease who have not been previously treated with immunomodulators. However,
      there are questions about the effect of withdrawing immunomodulator therapy from
      these patients. We studied the effects of treatment with infliximab and
      immunomodulators (co-treatment) and then immunomodulator withdrawal on long-term
      outcomes of patients, as well as trough levels of infliximab and formation of
      anti-infliximab antibodies (ATI). METHODS: In a retrospective study with the
      median follow-up period of 34 months (interquartile range, 19-58 months), we
      analyzed data from 223 patients treated for Crohn's disease between May 1999 and
      December 2010 at the University Hospitals, Leuven, Belgium (65 received
      infliximab monotherapy, 158 received infliximab and an immunomodulator). Trough
      levels of infliximab and levels of ATI were measured in blood samples collected
      from 117 patients throughout co-treatment, as well as the time of immunomodulator
      withdrawal and after withdrawal. RESULTS: Patients receiving co-treatment had
      higher trough levels of infliximab (adjusted mean increase, 1.44-fold) than those
      receiving infliximab monotherapy (95% confidence interval [CI], 1.07-1.92; P =
      .02). A smaller percentage of patients receiving co-treatment developed ATI (35
      of 158, 22%) than those receiving infliximab monotherapy (25 of 65, 38%; P =
      .01). Among co-treated patients, levels of infliximab remained stable after
      immunomodulators were withdrawn (before: 3.2 MUg/mL; 95% CI, 1.6-5.8 MUg/mL and
      after: 3.7 MUg/mL; 95% CI, 1.3-6.3 MUg/mL; P = .70). After withdrawal of
      immunomodulators, 45 of 117 patients (38%) required increasing doses of
      infliximab, and 21 of 117 (18%) discontinued infliximab. At the time of
      immunomodulator withdrawal, trough levels of infliximab and C-reactive protein
      were most strongly associated with response to infliximab thereafter.
      CONCLUSIONS: In a retrospective analysis, we confirmed that withdrawal of
      immunomodulators after at least 6 months (median, 13 months) of co-treatment with
      infliximab does not reduce the trough levels of infliximab in patients with
      Crohn's disease. Detectable trough levels of infliximab at the time of
      immunomodulator withdrawal are associated with long-term response.

PMID- 25066842
TI  - Processing speed impairment in schizophrenia is mediated by white matter
      integrity.
AB  - BACKGROUND: Processing speed predicts functional outcome and is a potential
      endophenotype for schizophrenia. Establishing the neural basis of processing
      speed impairment may inform the treatment and etiology of schizophrenia.
      Neuroimaging investigations in healthy subjects have linked processing speed to
      brain anatomical connectivity. However, the relationship between processing speed
      impairment and white matter (WM) integrity in schizophrenia is unclear. METHOD:
      Individuals with schizophrenia and healthy subjects underwent diffusion tensor
      imaging (DTI) and completed a brief neuropsychological assessment that included
      measures of processing speed, verbal learning, working memory and executive
      functioning. Group differences in WM integrity, inferred from fractional
      anisotropy (FA), were examined throughout the brain and the hypothesis that
      processing speed impairment in schizophrenia is mediated by diminished WM
      integrity was tested. RESULTS: WM integrity of the corpus callosum, cingulum,
      superior and inferior frontal gyri, and precuneus was reduced in schizophrenia.
      Average FA in these regions mediated group differences in processing speed but
      not in other cognitive domains. Diminished WM integrity in schizophrenia was
      accounted for, in large part, by individual differences in processing speed.
      CONCLUSIONS: Cognitive impairment in schizophrenia was mediated by reduced WM
      integrity. This relationship was strongest for processing speed because deficits
      in working memory, verbal learning and executive functioning were not mediated by
      WM integrity. Larger sample sizes may be required to detect more subtle mediation
      effects in these domains. Interventions that preserve WM integrity or ameliorate
      WM disruption may enhance processing speed and functional outcome in
      schizophrenia.

PMID- 25066843
TI  - Inhibition of poly-ADP ribose polymerase enzyme activity prevents hyperglycemia
      induced impairment of angiogenesis during wound healing.
AB  - We previously reported a zebrafish model of type I diabetes mellitus (DM) that
      can be used to study the hyperglycemic (HG) and metabolic memory (MM) states
      within the same fish. Clinically, MM is defined as the persistence of diabetic
      complications even after glycemic control is pharmacologically achieved. In our
      zebrafish model, MM occurs following beta-cell regeneration, which returns fish
      to euglycemia. During HG, fish acquire tissue deficits reflective of the
      complications seen in patients with DM and these deficits persist after fish
      return to euglycemia (MM). The unifying mechanism for the induction of diabetic
      complications involves a cascade of events that is initiated by the HG
      stimulation of poly-ADP ribose polymerase enzyme (Parp) activity. Additionally,
      recent evidence shows that the HG induction of Parp activity stimulates changes
      in epigenetic mechanisms that correlate with the MM state and the persistence of
      complications. Here we report that wound-induced angiogenesis is impaired in DM
      and remains impaired when fish return to a euglycemic state. Additionally,
      inhibition of Parp activity prevented the HG-induced wound angiogenesis
      deficiency observed. This approach can identify molecular targets that will
      provide potential new avenues for therapeutic discovery as angiogenesis
      imbalances are associated with all HG-damaged tissues. 

PMID- 25066844
TI  - Type I interferon rapidly restricts infectious hepatitis C virus particle
      genesis.
AB  - Interferon-alpha (IFNalpha) has been used to treat chronic hepatitis C virus
      (HCV) infection for over 20 years with varying efficacy, depending on the
      infecting viral genotype. The mechanism of action of IFNalpha is not fully
      understood, but is thought to target multiple stages of the HCV lifecycle,
      inhibiting viral transcription and translation leading to a degradation of viral
      RNA and protein expression in the infected cell. IFNalpha induces the expression
      of an array of interferon-stimulated genes within minutes of receptor engagement;
      however, the impact of these early responses on the viral lifecycle are unknown.
      We demonstrate that IFNalpha inhibits the genesis of infectious extracellular HCV
      particles within 2 hours of treating infected cells, with minimal effect on the
      intracellular viral burden. Importantly, this short duration of IFNalpha
      treatment of infected cells significantly reduced cell-free and cell-to-cell
      dissemination. The secreted viral particles showed no apparent change in protein
      content or density, demonstrating that IFNalpha inhibits particle infectivity but
      not secretion rates. To investigate whether particles released from IFNalpha
      treated cells have a reduced capacity to establish infection we used HCV
      lentiviral pseudotypes (HCVpp) and demonstrated a defect in cell entry. Using a
      panel of monoclonal antibodies targeting the E2 glycoprotein, we demonstrate that
      IFNalpha alters glycoprotein conformation and receptor utilization. CONCLUSION:
      These observations show a previously unreported and rapid effect of IFNalpha on
      HCV particle infectivity that inhibits de novo infection events. Evasion of this
      response may be a contributing factor in whether a patient achieves early or
      rapid virological response, a key indicator of progression to sustained
      virological response or clearance of viral infection.

PMID- 25066845
TI  - Health services research: evolution and applications.
AB  - Health services research (HSR) is broadly focused on characterizing and improving
      the access, quality, delivery, and cost of health care. HSR is a
      multidisciplinary field, engaging experts in clinical medicine and surgery,
      policy, economics, implementation science, statistics, psychology, and education
      to improve the care of patients across all specialties. This article summarizes
      the evolution and distinctive attributes of HSR and present several real-world
      applications. 

PMID- 25066846
TI  - Evidence-based medicine in hand surgery: clinical applications and future
      direction.
AB  - Evidence-based medicine empowers physicians to systematically analyze published
      data so as to quickly formulate treatment plans that deliver safe, robust, and
      cost-effective patient care. In this article, we sample some areas in hand and
      upper extremity surgery where the evidence base is strong enough that it has or
      should have unified treatment strategies; we identify some problems where good
      evidence has failed to unify treatment, and discuss problems for which evidence
      is still lacking but needed because treatment remains controversial. We also
      discuss circumstances in which level 4 evidence is more likely than randomized
      trials to guide treatment. 

PMID- 25066847
TI  - Measuring and understanding treatment effectiveness in hand surgery.
AB  - Incorporating evidence-based medicine into practice is now an expectation for
      hand surgeons. Hand surgeons need to be able to assess associated benefits,
      risks, cost, and applicability of a treatment option when providing care to their
      patients. Using a clinical example, this article takes the reader through the
      three-step approach when using a publication from the medical literature on
      therapy. The focus of this article is primarily the second and third steps, which
      involve measuring and understanding treatment effectiveness. 

PMID- 25066848
TI  - Patient-reported outcomes: state-of-the-art hand surgery and future applications.
AB  - Patient-reported outcome measures (PRO) can provide reliable and valid estimates
      of patient status and response to interventions to complete the final step in an
      evidence-based patient interaction. A variety of PRO are relevant to upper
      extremity surgery and rehabilitation outcomes. PRO provide feasible tools for
      clinical research or practice, although use in clinical decision making lags
      behind research applications. Recent trends in clinical measurement include
      better integration of International Classification of Functioning, Disability and
      Health in content validation, more modern methods of evaluating scaling
      properties (Rasch analysis), consensus exercise on establishing core measures,
      electronic data collection, and computer-adaptive testing. 

PMID- 25066849
TI  - Bench to bedside: integrating advances in basic science into daily clinical
      practice.
AB  - This article focuses on the initial steps of commercial development of a
      patentable scientific discovery from an academic center through to marketing a
      clinical product. The basics of partnering with a technology transfer office
      (TTO) and the complex process of patenting are addressed, followed by a
      discussion on marketing and licensing the patent to a company in addition to
      starting a company. Finally, the authors address the basic principles of
      obtaining clearance from the Food and Drugs Administration, production in a good
      manufacturing practice (GMP) facility, and bringing the product to clinical
      trial. 

PMID- 25066850
TI  - Comparative effectiveness research in hand surgery.
AB  - Comparative effectiveness research (CER) is a concept initiated by the Institute
      of Medicine and financially supported by the federal government. The primary
      objective of CER is to improve decision making in medicine. This research is
      intended to evaluate the effectiveness, benefits, and harmful effects of
      alternative interventions. CER studies are commonly large, simple, observational,
      and conducted using electronic databases. To date, there is little comparative
      effectiveness evidence within hand surgery to guide therapeutic decisions. To
      draw conclusions on effectiveness through electronic health records, databases
      must contain clinical information and outcomes relevant to hand surgery
      interventions, such as patient-related outcomes. 

PMID- 25066851
TI  - Quality assessment in hand surgery.
AB  - Measuring quality assessment in hand surgery remains an underexplored area.
      However, measuring quality is becoming increasingly transparent and important.
      Patients now have direct access to hospital and physician metrics and large
      payers have linked financial incentives to quality metrics. It is critical for
      hand surgeons to understand the essential elements of quality and its assessment.
      This article reviews several areas of hand surgery quality assessments including
      safety, outcomes, satisfaction, and cost. 

PMID- 25066852
TI  - Collaborative quality improvement in surgery.
AB  - Collaborative quality improvement has demonstrated success in improving quality
      and reducing health care costs in several state-based examples. Professional
      societies and payers are keen on identifying the most effective strategies to
      improve the safety and efficiency of surgical care. This review highlights the
      development and features of collaborative quality improvement programs, their
      advantages and examples of successful collaborations for several surgical
      conditions, and their potential application for surgeons caring for patients with
      upper extremity trauma and disability. 

PMID- 25066853
TI  - The patient protection and Affordable Care Act: a primer for hand surgeons.
AB  - The Affordable Care Act is the largest and most comprehensive overhaul of the
      United States health care industry since the inception of the Medicare and
      Medicaid. Contained within the 10 titles are a multitude of provisions that will
      change how hand surgeons practice medicine and how they are reimbursed. It is
      imperative that surgeons are equipped with the knowledge of how this law will
      affect all physician practices and hospitals. 

PMID- 25066854
TI  - Patient-centered care in medicine and surgery: guidelines for achieving patient
      centered subspecialty care.
AB  - Patient-centered care is based on the principle that equality between physician
      and patient is mutually advantageous. This model of care recently has largely
      supplanted the historical paternalistic model of the physician-patient
      relationship. Patient-centered care differs from the disease-centered model of
      evidence-based medicine, but the two are not mutually exclusive. Patient-centered
      care has 5 core components: the biopsychosocial perspective, the patient as
      person, sharing power and responsibility, the therapeutic alliance, and the
      doctor as person. This article explores these components, explains the
      differences between patient-centered care and evidence-based medicine, and offers
      guidelines for achieving patient-centered subspecialty care in hand surgery. 

PMID- 25066855
TI  - Clinical practice guidelines: what are they and how should they be disseminated?
AB  - Clinical practice guidelines summarize the available evidence for patient
      management in a format that is easy for clinicians to use. These guidelines
      usually use methodologically rigorous principles for retrieving and evaluating
      the literature and for establishing consensus among work group members, but
      implementation by clinicians is often incomplete. The reasons why guidelines fail
      to gain widespread acceptance vary with the topic and clinician group. Successful
      dissemination of practice guidelines requires an understanding of the barriers to
      implementation and the use of multiple strategies to address these. This article
      examines the factors affecting implementation and the approaches to overcoming
      these obstacles. 

PMID- 25066856
TI  - Funding research in the twenty-first century: current opinions and future
      directions.
AB  - For all academic biomedical researchers, the process of submitting grants and
      securing research funding is a critical part of advancing one's career. In the
      current era of decreasing new grant awards and renewals leading to significantly
      worse success rates, it is hard for young aspiring physician-scientists to remain
      optimistic regarding their future in academic medicine. It is important that
      today's young surgeon-scientists prepare for and adapt to the inevitably changing
      climate of research funding. This article provides a primer on developing a
      successful career as a funded surgeon-scientist and pathways for building a
      robust research platform worthy of extramural National Institutes of Health
      funding in the twenty-first century. 

PMID- 25066857
TI  - Future education and practice initiatives in hand surgery: improving fulfillment
      of patient needs.
AB  - In the current health care environment, there are several areas in the delivery
      of health care to patients having hand surgery that need improvement to
      adequately fulfill patient needs, including difficulty in maintaining adequate
      emergency call coverage for patients having hand surgery, decreasing trends in
      hand surgeons willing to perform microsurgery and replantation, and deficiencies
      in musculoskeletal education of non-hand surgery providers. Both educational
      reforms and reforms in the practice environment are needed to improve the ability
      of hand surgeons to fulfill patient needs in the future. 

PMID- 25066858
TI  - Evidence-based medicine in hand surgery.

PMID- 25066859
TI  - An oncofetal and developmental perspective on testicular germ cell cancer.
AB  - Germ cell tumors (GCTs) represent a diverse group of tumors presumably
      originating from (early fetal) developing germ cells. Most frequent are the
      testicular germ cell cancers (TGCC). Overall, TGCC is the most frequent
      malignancy in Caucasian males (20-40 years) and remains an important cause of
      (treatment related) mortality in these young men. The strong association between
      the phenotype of TGCC stem cell components and their totipotent ancestor (fetal
      primordial germ cell or gonocyte) makes these tumors highly relevant from an onco
      fetal point of view. This review subsequently discusses the evidence for the
      early embryonic origin of TGCCs, followed by an overview of the crucial
      association between TGCC pathogenesis, genetics, environmental exposure and the
      (fetal) testicular micro-environment (genvironment). This culminates in an
      evaluation of three genvironmentally modulated hallmarks of TGCC directly related
      to the oncofetal pathogenesis of TGCC: (1) maintenance of pluripotency, (2) cell
      cycle control/cisplatin sensitivity and (3) regulation of
      proliferation/migration/apoptosis by KIT-KITL mediated receptor tyrosine kinase
      signaling. Briefly, TGCC exhibit identifiable stem cell components (seminoma and
      embryonal carcinoma) and progenitors that show large and consistent similarities
      to primordial/embryonic germ cells, their presumed totipotent cells of origin.
      TGCC pathogenesis depends crucially on a complex interaction of genetic and
      (micro-)environmental, i.e. genvironmental risk factors that have only been
      partly elucidated despite significant effort. TGCC stem cell components also show
      a high degree of similarity with embryonic stem/germ cells (ES) in the regulation
      of pluripotency and cell cycle control, directly related to their exquisite
      sensitivity to DNA damaging agents (e.g. cisplatin). Of note, (ES specific) micro
      RNAs play a pivotal role in the crossover between cell cycle control,
      pluripotency and chemosensitivity. Moreover, multiple consistent observations
      reported TGCC to be associated with KIT-KITL mediated receptor tyrosine kinase
      signaling, a pathway crucially implicated in proliferation, migration and
      survival during embryogenesis including germ cell development. In conclusion,
      TGCCs are a fascinating model for onco-fetal developmental processes especially
      with regard to studying cell cycle control, pluripotency maintenance and KIT-KITL
      signaling. The knowledge presented here contributes to better understanding of
      the molecular characteristics of TGCC pathogenesis, translating to identification
      of at risk individuals and enhanced quality of care for TGCC patients (diagnosis,
      treatment and follow-up).

PMID- 25066860
TI  - Evolving paradigms in multifocal breast cancer.
AB  - The 7th edition of the TNM defines multifocal breast cancer as multiple
      simultaneous ipsilateral and synchronous breast cancer lesions, provided they are
      macroscopically distinct and measurable using current traditional pathological
      and clinical tools. According to the College of American Pathologists (CAP), the
      characterization of only the largest lesion is considered sufficient, unless the
      grade and/or histology are different between the lesions. Here, we review three
      potentially clinically relevant aspects of multifocal breast cancers: first, the
      importance of a different intrinsic breast cancer subtype of the various lesions;
      second, the emerging awareness of inter-lesion heterogeneity; and last but not
      least, the potential introduction of bias in clinical trials due to the
      unrecognized biological diversity of these cancers. Although the current strategy
      to assess the lesion with the largest diameter has clearly its advantages in
      terms of costs and feasibility, this recommendation may not be sustainable in
      time and might need to be adapted to be compliant with new evolving paradigms in
      breast cancer. 

PMID- 25066861
TI  - Understanding and exploiting 5T4 oncofoetal glycoprotein expression.
AB  - Oncofoetal antigens are present during foetal development with generally limited
      expression in the adult but are upregulated in cancer. These molecules can
      sometimes be used to diagnose or follow treatment of tumours or as a target for
      different immunotherapies. The 5T4 oncofoetal glycoprotein was identified by
      searching for shared surface molecules of human trophoblast and cancer cells with
      the rationale that they may function to allow survival of the foetus as a semi
      allograft in the mother or a tumour in its host, potentially influencing growth,
      invasion or altered immune surveillance of the host. 5T4 tumour selective
      expression has stimulated the development of 5T4 vaccine, 5T4 antibody targeted
      superantigen and 5T4 antibody-drug therapies through preclinical and into
      clinical studies. It is now apparent that 5T4 expression is a marker of the use
      (or not) of several cellular pathways relevant to tumour growth and spread. Thus
      5T4 expression is mechanistically associated with the directional movement of
      cells through epithelial mesenchymal transition, facilitation of CXCL12/CXCR4
      chemotaxis, blocking of canonical Wnt/beta-catenin while favouring non-canonical
      pathway signalling. These processes are highly regulated in development and in
      normal adult tissues but can contribute to the spread of cancer cells.
      Understanding the differential impact of these pathways marked by 5T4 can
      potentially improve existing, or aid development of novel cancer treatment
      strategies.

PMID- 25066862
TI  - Designing and implementing INTREPID, an intensive program in translational
      research methodologies for new investigators.
AB  - Senior housestaff and junior faculty are often expected to perform clinical
      research, yet may not always have the requisite knowledge and skills to do so
      successfully. Formal degree programs provide such knowledge, but require a
      significant commitment of time and money. Short-term training programs (days to
      weeks) provide alternative ways to accrue essential information and acquire
      fundamental methodological skills. Unfortunately, published information about
      short-term programs is sparse. To encourage discussion and exchange of ideas
      regarding such programs, we here share our experience developing and implementing
      INtensive Training in Research Statistics, Ethics, and Protocol Informatics and
      Design (INTREPID), a 24-day immersion training program in clinical research
      methodologies. Designing, planning, and offering INTREPID was feasible, and
      required significant faculty commitment, support personnel and infrastructure, as
      well as committed trainees. 

PMID- 25066863
TI  - Hazardous drinking and HIV-risk-related behavior among male clients of female sex
      workers in Tijuana, Mexico.
AB  - BACKGROUND AND OBJECTIVES: Male clients of female sex workers (FSWs) are at high
      risk for HIV. Whereas the HIV risks of alcohol use are well understood, less is
      known about hazardous alcohol use among male clients of FSWs, particularly in
      Mexico. We sought to identify risk factors for hazardous alcohol use and test
      associations between hazardous alcohol use and HIV risk behavior among male
      clients in Tijuana. METHOD: Male clients of FSWs in Tijuana (n = 400) completed a
      quantitative interview in 2008. The AUDIT was used to characterize hazardous
      alcohol use. Multivariate logistic regression was used to determine independent
      associations of demographic and HIV risk variables with hazardous alcohol use
      (vs. non-hazardous). RESULTS: Forty percent of our sample met criteria for
      hazardous alcohol use. Variables independently associated with hazardous drinking
      were reporting any sexually transmitted infection (STI), having sex with a FSW
      while under the influence of alcohol, being younger than 36 years of age, living
      in Tijuana, and ever having been jailed. Hazardous drinkers were less likely ever
      to have been deported or to have shared injection drugs. DISCUSSION AND
      CONCLUSIONS: Hazardous alcohol use is associated with HIV risk, including
      engaging in sex with FSWs while intoxicated and having an STI among male clients
      of FSWs in Tijuana. SCIENTIFIC SIGNIFICANCE: We systematically described patterns
      and correlates of hazardous alcohol use among male clients of FSWs in Tijuana,
      Mexico. The results suggest that HIV/STI risk reduction interventions must target
      hazardous alcohol users, and be tailored to address alcohol use.

PMID- 25066864
TI  - Lysosome size, motility and stress response regulated by fronto-temporal dementia
      modifier TMEM106B.
AB  - Fronto-temporal lobar degeneration with TDP-43 (FTLD-TDP) is a fatal
      neurodegeneration. TMEM106B variants are linked to FTLD-TDP risk, and TMEM106B is
      lysosomal. Here, we focus on neuronal TMEM106B, and demonstrate co-localization
      and traffic with lysosomal LAMP-1. pH-sensitive reporters demonstrate that the
      TMEM106B C-terminus is lumenal. The TMEM106B N-terminus interacts with endosomal
      adaptors and other TMEM106 proteins. TMEM106B knockdown reduces neuronal
      lysosomal number and diameter by STED microscopy, and overexpression enlarges
      LAMP-positive structures. Reduction of TMEM106B increases axonally transported
      lysosomes, while TMEM106B elevation inhibits transport and yields large lysosomes
      in the soma. TMEM106B overexpression alters lysosomal stress signaling, causing a
      translocation of the mTOR-sensitive transcription factor, TFEB, to neuronal
      nuclei. TMEM106B loss-of-function delays TFEB translocation after Torin-1-induced
      stress. Enlarged TMEM106B-overexpressing lysosomes maintain organelle integrity
      longer after lysosomal photodamage than do control lysosomes, while small
      TMEM106B-knockdown lysosomes are more sensitive to illumination. Thus, neuronal
      TMEM106B plays a central role in regulating lysosomal size, motility and
      responsiveness to stress, highlighting the possible role of lysosomal biology in
      FTLD-TDP.

PMID- 25066866
TI  - Differences in prefrontal blood oxygenation during an acute multitasking stressor
      in ecstasy polydrug users.
AB  - BACKGROUND: Cognitive deficits are well documented in ecstasy (3,4
      methylenedioxymethamphetamine; MDMA) users, with such deficits being taken as
      evidence of dysregulation of the serotonin (5-hydroxytryptamine; 5-HT) system.
      More recently neuroimaging has been used to corroborate these deficits. The
      present study aimed to assess multitasking performance in ecstasy polydrug users,
      polydrug users and drug-naive individuals. It was predicted that ecstasy polydrug
      users would perform worse than non-users on the behavioural measure and this
      would be supported by differences in cortical blood oxygenation. METHOD: In the
      study, 20 ecstasy-polydrug users, 17 polydrug users and 19 drug-naive individuals
      took part. On day 1, drug use history was taken and questionnaire measures were
      completed. On day 2, participants completed a 20-min multitasking stressor while
      brain blood oxygenation was measured using functional near infrared spectroscopy
      (fNIRS). RESULTS: There were no significant differences between the three groups
      on the subscales of the multitasking stressor. In addition, there were no
      significant differences on self-report measures of perceived workload (NASA Task
      Load Index). In terms of mood, ecstasy users were significantly less calm and
      less relaxed compared with drug-naive controls. There were also significant
      differences at three voxels on the fNIRS, indicating decreased blood oxygenation
      in ecstasy users compared with drug-naive controls at voxel 2 (left dorsolateral
      prefrontal cortex), voxel 14 and voxel 16 (right dorsolateral prefrontal cortex),
      and compared with polydrug controls at V14. CONCLUSIONS: The results of the
      present study provide support for changes in brain activation during performance
      of demanding tasks in ecstasy polydrug users, which could be related to cerebral
      vasoconstriction.

PMID- 25066865
TI  - Postsynaptic actin regulates active zone spacing and glutamate receptor
      apposition at the Drosophila neuromuscular junction.
AB  - Synaptic communication requires precise alignment of presynaptic active zones
      with postsynaptic receptors to enable rapid and efficient neurotransmitter
      release. How transsynaptic signaling between connected partners organizes this
      synaptic apparatus is poorly understood. To further define the mechanisms that
      mediate synapse assembly, we carried out a chemical mutagenesis screen in
      Drosophila to identify mutants defective in the alignment of active zones with
      postsynaptic glutamate receptor fields at the larval neuromuscular junction. From
      this screen we identified a mutation in Actin 57B that disrupted synaptic
      morphology and presynaptic active zone organization. Actin 57B, one of six actin
      genes in Drosophila, is expressed within the postsynaptic bodywall musculature.
      The isolated allele, act(E84K), harbors a point mutation in a highly conserved
      glutamate residue in subdomain 1 that binds members of the Calponin Homology
      protein family, including spectrin. Homozygous act(E84K) mutants show impaired
      alignment and spacing of presynaptic active zones, as well as defects in
      apposition of active zones to postsynaptic glutamate receptor fields. act(E84K)
      mutants have disrupted postsynaptic actin networks surrounding presynaptic
      boutons, with the formation of aberrant actin swirls previously observed
      following disruption of postsynaptic spectrin. Consistent with a disruption of
      the postsynaptic actin cytoskeleton, spectrin, adducin and the PSD-95 homolog
      Discs-Large are all mislocalized in act(E84K) mutants. Genetic interactions
      between act(E84K) and neurexin mutants suggest that the postsynaptic actin
      cytoskeleton may function together with the Neurexin-Neuroligin transsynaptic
      signaling complex to mediate normal synapse development and presynaptic active
      zone organization.

PMID- 25066867
TI  - Frequent coexistence of RAS mutations in RUNX1-mutated acute myeloid leukemia in
      Arab Asian children.
AB  - BACKGROUND: RUNX1 mutation plays an important role in adult leukemic
      transformation. However, its contribution to the development of childhood
      leukemia remains unclear. In the present study, we analyzed point mutations of
      RUNX1 gene in children and adolescents with acute myeloid leukemia (AML) from
      Iraq and Jordan. PROCEDURE: Bone marrow and/or peripheral blood samples were
      collected from 178 patients of Arab Asian ethnicity (aged <=17 years) newly
      diagnosed with AML: 145 samples from Iraq and 33 samples from Jordan. Direct DNA
      sequencing was performed on six genes including RUNX1 gene (exons 3-8). RESULTS:
      RUNX1 point mutations were identified in 10 (5.6%) of 178 patients. One patient
      possessed biallelic mutations of RUNX1 gene. C-terminal area was the predominant
      site of RUNX1 mutations (eight in C-terminal and two in N-terminal). Patients
      with RUNX1 mutations were significantly older than those with wild-type of the
      gene. Additionally, AML M0 subtype was more frequently found in patients with
      RUNX1 mutations. Both RUNX1 mutations and RAS mutations were identified in 4 of
      10 children. Three patients with RUNX1 mutation had FLT3-ITD. On the other hand,
      36 (21.4%) and 25 (14.9%) of 168 patients with wild-type of the gene had a RAS
      mutation and FLT3-ITD, respectively. Eight of 10 patients with RUNX1 mutations
      died of hematological relapse. CONCLUSION: The incidence of RUNX1 mutations in
      Arab Asian children and adolescents with AML was 5.6%. Further studies are
      required to clarify whether RAS mutations contribute to the development of
      pediatric AML associated with RUNX1 mutations.

PMID- 25066868
TI  - Feasibility of intraoperative navigation to the sentinel node in the groin using
      preoperatively acquired single photon emission computerized tomography data:
      transferring functional imaging to the operating room.
AB  - PURPOSE: We explored the clinical feasibility and accuracy of intraoperative
      navigation based on preoperatively acquired 3-dimensional functional imaging
      data. MATERIALS AND METHODS: Ten patients with penile carcinoma scheduled for
      sentinel node biopsy were prospectively included in study. After tracer injection
      preoperative single photon emission computerized tomography/computerized
      tomography was performed with a reference target fixed on the patient.
      Repositioning a sterile reference target shortly before surgery allowed 3
      dimensional single photon emission computerized tomography/computerized
      tomography mixed reality based navigation of the gamma probe (also containing a
      reference target) to the sentinel node. The accuracy of the declipse(r)SPECT
      navigation approach was determined in relation to the incision site indicated by
      the conventional gamma probe in the coronal plane and the depth estimation
      measured on axial computerized tomography slices in the sagittal/axial plane.
      RESULTS: The 3-dimensional mixed reality approach enabled gamma probe navigation
      toward the sentinel node in all 10 patients. The average +/- SD navigation error
      in the coronal and saggital/axial planes was 5.0 +/- 3.9 and 5.3 +/- 3.9 mm,
      respectively. CONCLUSIONS: To our knowledge this is the first study demonstrating
      the feasibility of intraoperative navigation based on preoperatively acquired 3
      dimensional single photon emission computerized tomography/computerized
      tomography images. Although confirmation of successful target localization (eg
      using gamma tracing or fluorescence imaging) remains indispensable, this opens
      the way to translate 3-dimensional functional imaging data to the operating room.

PMID- 25066869
TI  - A prospective, randomized comparison of shock wave lithotripsy, retrograde
      intrarenal surgery and miniperc for treatment of 1 to 2 cm radiolucent lower
      calyceal renal calculi: a single center experience.
AB  - PURPOSE: A prospective, randomized comparison of shock wave lithotripsy,
      retrograde intrarenal surgery and miniperc for the treatment of 1 to 2 cm
      radiolucent lower calyceal renal calculi was done to evaluate the safety and
      efficacy of these procedures. MATERIALS AND METHODS: Patients with a single 1 to
      2 cm radiolucent lower calyceal renal stone who underwent treatment between
      January 2012 and May 2013 were included in study. They were randomized to shock
      wave lithotripsy, retrograde intrarenal surgery and miniperc groups. Patient
      demographic profiles, success and re-treatment rates, auxiliary procedures and
      complications were analyzed. RESULTS: A total of 45 patients were enrolled in
      each of the shock wave lithotripsy, retrograde intrarenal surgery and miniperc
      groups. Three, 2 and 4 patients, respectively, were excluded from final analysis
      due to a matrix stone diagnosis. Mean procedure and fluoroscopy times were
      significantly greater in the miniperc group than in the other groups. Hospital
      stay (3.1 days vs 3.1 hours and 1.3 days, p = 0.01) and the blood transfusion
      rate (13.3% vs 0% and 0%, p = 0.03) were significantly higher for miniperc vs
      shock wave lithotripsy and retrograde intrarenal surgery, respectively. The re
      treatment rate (63.4% vs 2.1% and 2.2%, p <0.001) and the auxiliary procedure
      rate (20.2% vs 8.8% and 6.6%, p = 0.02) were significantly greater for shock wave
      lithotripsy than for retrograde intrarenal surgery and miniperc, respectively.
      The 3-month stone-free rate of shock wave lithotripsy, retrograde intrarenal
      surgery and miniperc was 73.8% (31 of 42 patients), 86.1% (37 of 43) and 95.1%
      (39 of 41), respectively (p = 0.01). CONCLUSIONS: Miniperc and retrograde
      intrarenal surgery were more effective than shock wave lithotripsy to treat 1 to
      2 cm radiolucent lower calyceal renal calculi in terms of a better stone-free
      rate, and lesser auxiliary and re-treatment rates. However, miniperc resulted in
      more complications, greater operative time and radiation exposure, and a longer
      hospital stay.

PMID- 25066870
TI  - Donation after cardiac death pediatric en bloc renal transplantation.
AB  - PURPOSE: Use of small pediatric kidneys obtained from extremely young donors
      after cardiac death has been limited. This potential organ source remains under
      used by transplant teams. MATERIALS AND METHODS: We reviewed all renal
      transplants at our institution from 2000 to 2013 to identify recipients of an en
      bloc pair of kidneys from deceased pediatric donors younger than 4 years. The
      outcomes of donation after cardiac death en bloc allografts were compared with
      neurological determination of death en bloc allografts. RESULTS: A total of 21
      recipients of en bloc renal allografts were identified, of which 4 organ pairs
      were obtained through donation after cardiac death. Mean +/- SD donor age was
      20.6 +/- 11.6 months and weight was 12.4 +/- 3.7 kg. Delayed allograft function
      occurred in 2 of 4 recipients of allografts obtained from donation after cardiac
      death en bloc and 3 of 17 recipients of allografts from neurological
      determination of death en bloc. One year after transplantation mean +/- SD
      glomerular filtration rates were similar, at 80.7 +/- 15.3 and 85.7 +/- 33.4
      ml/minute/1.73 m(2) in the cardiac and neurological allograft groups,
      respectively (difference not significant). Surgical complications occurred in 3
      patients, and no allograft was lost to thrombosis. CONCLUSIONS: We report
      successful transplantation of a small cohort of pediatric en bloc kidneys
      obtained through donation after cardiac death from donors younger than 4 years.
      Outcomes at 1 year are comparable to those in neurological determination of death
      en bloc allograft recipients.

PMID- 25066871
TI  - Reservoir alternate surgical implantation technique: preliminary outcomes of
      initial PROPPER study of low profile or spherical reservoir implantation in
      submuscular location or traditional prevesical space.
AB  - PURPOSE: Alternative reservoir site placement has become an accepted technique
      for patients who require an inflatable penile prosthesis. To our knowledge there
      has been no prospective evaluation of this technique, which is currently off
      label. We performed a prospective, multicenter, multinational, internal review
      board approved study to evaluate the effectiveness and safety of alternative
      reservoir site placement. MATERIALS AND METHODS: PROPPER initiated in June 2011,
      is a database containing patient outcomes of inflatable penile prosthesis
      implantation. Patients with AMS(r) penile prostheses continue to be enrolled at
      13 North American sites. We examined PROPPER study data to determine surgical
      implantation use patterns for the AMS 700TM series. We evaluated reservoir
      implantation site and complications by implantation site. RESULTS: A total of 759
      patients had been implanted with an AMS 700 series implant by the time of
      evaluation. Mean patient followup was 17.8 months (range 0 to 36). There was no
      reported case of revision surgery for a palpable reservoir and no report of
      vascular or hollow viscous injury associated with alternative reservoir site
      placement. Two cases of reservoir herniation in the alternative reservoir site
      placement group and 2 in the space of Retzius group were treated with reservoir
      reimplantation. Patients with 1-year assessment available were satisfied or very
      satisfied with the device and reported a frequency of use of more than once per
      month. CONCLUSIONS: Alternative reservoir placement in the submuscular location
      is an option in patients who undergo inflatable penile prosthesis surgery.
      Implant surgeons should consider alternative reservoir site placement a safe,
      effective alternative to reservoir placement in the space of Retzius.

PMID- 25066873
TI  - Comparison of transvaginal and retropubic bladder neck closure with suprapubic
      catheter in women.
AB  - PURPOSE: Bladder neck closure is an uncommon procedure that is usually reserved
      for patients with severe urethral incompetence. It may be an acceptable
      alternative to procedures involving bowel reconstruction. Bladder neck closure
      can be performed using a transvaginal or a retropubic approach. We compared
      urethral continence rates, perioperative outcomes, short-term and long-term
      complications, subsequent procedures and changes in renal function between
      transvaginal and retropubic bladder neck closure in females at our institution.
      MATERIALS AND METHODS: We retrospectively reviewed the records of 64 female
      patients who underwent bladder neck closure with suprapubic catheter placement
      from May 1990 to February 2013. Baseline variables and the mentioned outcomes
      were compared between transvaginal and retropubic bladder neck closure. RESULTS:
      There were 35 women in the transvaginal group and 29 in the retropubic group.
      Urethral erosion due to a chronic indwelling urethral catheter was the most
      common indication for bladder neck closure. The urethral continence rate after
      the first bladder neck closure did not significantly differ between the
      transvaginal and retropubic groups (85.7% vs 81.5%, p = 0.74). The transvaginal
      group had significantly shorter mean operative time (78.0 vs 137.5 minutes, p =
      0.002) and hospital stay (1.5 vs 4.9 days, p = 0.0003), and fewer short-term
      complications (5.7% vs 31.0%, p = 0.02) than the retropubic group. The remaining
      outcomes did not differ between the 2 groups. CONCLUSIONS: There was no
      difference between transvaginal and retropubic bladder neck closure in achieving
      urethral continence. Transvaginal bladder neck closure was associated with a
      shorter operative time and hospital stay as well as fewer short-term
      complications.

PMID- 25066872
TI  - Impact of family history on prostate cancer mortality in white men undergoing
      prostate specific antigen based screening.
AB  - PURPOSE: We assessed whether prostate cancer screening would decrease prostate
      cancer mortality in white men with a family history of prostate cancer. MATERIALS
      AND METHODS: Data from the PLCO cancer screening trial were used to compare the
      screening and usual care arms in the subset of men with and without a family
      history of prostate cancer. Univariate and multivariate Cox regression analysis,
      and log rank analysis of Kaplan-Meier curves were done to examine the data for
      differences in prostate cancer specific survival. RESULTS: A total of 65,179
      white subjects were included in the prostate specific antigen screening trial, of
      whom 7,314 (11.2%) were diagnosed with prostate cancer. Only 4,833 white men
      (7.4%) had a family history of prostate cancer. Those with a positive family
      history had a significantly higher incidence of prostate cancer (16.9% vs 10.8%)
      and higher prostate cancer specific mortality (0.56% vs 0.37%, each p <0.01). On
      multivariate analysis this trended toward significance (HR 1.47, 95% CI 0.98
      2.21, p = 0.06). Screening in men with a positive family history also showed a
      trend toward decreased prostate cancer specific mortality (HR 0.49, 95% CI 0.22
      1.1, p = 0.08) and decreased time to death from prostate cancer (log rank p =
      0.05). CONCLUSIONS: White men with a family history of prostate cancer are at
      increased risk for being diagnosed with and subsequently dying of prostate
      cancer. Yearly digital rectal examination and prostate specific antigen testing
      may decrease prostate cancer death in these individuals.

PMID- 25066874
TI  - Bladder reinnervation using a primarily motor donor nerve (femoral nerve
      branches) is functionally superior to using a primarily sensory donor nerve
      (genitofemoral nerve).
AB  - PURPOSE: We determined whether transfer of a primarily motor nerve (femoral) to
      the anterior vesicle branch of the pelvic nerve would allow for more effective
      bladder reinnervation than transfer of a primarily sensory nerve (genitofemoral).
      MATERIALS AND METHODS: A total of 41 female mongrel dogs underwent bladder
      decentralization and then bilateral nerve transfer, or served as sham operated or
      unoperated controls. Decentralization was achieved by bilateral transection of
      all sacral roots that induced bladder contraction upon electrical stimulation.
      Retrograde neuronal labeling dye was injected in the bladder 3 weeks before
      sacrifice. RESULTS: Increased detrusor pressure after direct stimulation of the
      transferred nerve, lumbar spinal cord or spinal root was observed in 12 of 17
      dogs with genitofemoral nerve transfer and in 9 of 10 with femoral nerve transfer
      (mean +/- SEM 7.6 +/- 1.4 and 11.7 +/- 3.1 cm H2O, respectively). Mean detrusor
      pressure after direct electrical stimulation of transferred femoral nerves was
      statistically significantly greater than after stimulation of transferred
      genitofemoral nerves. Retrograde labeled neurons from the bladder observed in
      upper lumbar cord segments after genitofemoral and femoral nerve transfer
      confirmed bladder reinnervation, as did labeled axons at the nerve transfer site.
      CONCLUSIONS: While transfer of a mixed sensory and motor nerve (genitofemoral) or
      a primarily motor nerve (femoral) can reinnervate the bladder, using the
      primarily motor nerve provided greater return of nerve evoked detrusor
      contraction. This surgical approach may be useful to achieve bladder emptying in
      patients with lower motor spinal cord injury.

PMID- 25066875
TI  - Prostate capsule sparing versus nerve sparing radical cystectomy for bladder
      cancer: results of a randomized, controlled trial.
AB  - PURPOSE: Prostate capsule sparing and nerve sparing cystectomies are alternative
      procedures for bladder cancer that may decrease morbidity while achieving cancer
      control. However, to our knowledge the comparative effectiveness of these
      approaches has not been established. We evaluated functional and oncologic
      outcomes in patients undergoing these procedures. MATERIALS AND METHODS: We
      performed a single institution trial in patients with bladder cancer in whom
      transurethral prostatic urethral biopsy and transrectal prostate biopsy were
      negative. Men were randomized to prostate capsule sparing or nerve sparing
      cystectomy with neobladder creation and stratified by Sexual Health Inventory for
      Men score (greater than 21 vs 21 or less). Our primary end point was 12-month
      overall urinary function as measured by Bladder Cancer Index. Secondary end
      points included sexual function, cancer control and complications. RESULTS: A
      total of 40 patients were enrolled in the study with 20 patients in each arm.
      Urinary function at 12 months decreased by 13 and 28 points in the prostate
      capsule and nerve sparing groups, respectively (p = 0.10). Sexual function
      followed a similar pattern (p = 0.06). There was no difference in recurrence
      free, metastasis-free or overall survival (each p >0.05). The rate of
      incidentally detected prostate cancer was similar (p = 0.15). CONCLUSIONS: Our
      study provides a randomized comparison of prostate capsule sparing and nerve
      sparing cystectomy techniques. We found no difference in functional or oncologic
      outcomes between the 2 approaches, although our study was underpowered due to a
      lack of patient accrual.

PMID- 25066876
TI  - Same-day and delayed reports of pain intensity in second-trimester medical
      termination of pregnancy: a brief report.
AB  - OBJECTIVE: To assess same-day and delayed reports of pain intensity during and
      after second-trimester medical termination of pregnancy (MTOP). STUDY DESIGN: A
      prospective randomized trial (217 women) comparing 1- and 2-day mifepristone
      misoprostol intervals. RESULTS: Women reported intense pain [median visual
      analogue scale (interquartile range)] related to expulsion of the fetus [6 (0
      10)]. Delayed reports of maximal pain described the pain as more intense than
      same-day reports [8 (3-10) vs. 7 (1-10), p<.001]. CONCLUSIONS: Most women
      reported and readily remembered intense pain associated with fetal expulsion
      during second-trimester MTOP. IMPLICATIONS: Adequate, properly timed pain
      management during second-trimester MTOP is crucial.

PMID- 25066877
TI  - Doses and lung cancer risks from exposure to radon and plutonium.
AB  - PURPOSE: Epidemiological studies of the French uranium miners and the plutonium
      workers at the Mayak nuclear facility have provided excess relative risk (ERR)
      estimates per unit absorbed lung dose from alpha radiation. The aim of this paper
      was to review these two studies and to derive values of the relative biological
      effectiveness (RBE) of alpha particles for the induction of lung cancer.
      MATERIALS AND METHODS: We examined and compared the dosimetry assumptions and
      methodology used in the epidemiological studies of uranium miners and the
      plutonium workers. Values of RBE were obtained by comparing risk coefficients
      including comparison of lifetime risks for a given population. To do this,
      preliminary calculations of lifetime risks following inhalation of plutonium were
      carried out. RESULTS AND CONCLUSIONS: Published values of risk per unit dose
      following inhalation of radon progeny and plutonium were in agreement despite the
      very different dose distributions within the lungs and the different ways the
      doses were calculated. Values of RBE around 10-20 were obtained by comparing ERR
      values, but with wide uncertainty ranges. Comparing lifetime risks gave similar
      values (10, 19 and 21). This supports the use of a radiation weighting factor of
      20 for alpha particles for radiation protection purposes.

PMID- 25066879
TI  - Intra-articular lidocaine versus intravenous analgesia and sedation for manual
      closed reduction of acute anterior shoulder dislocation: an updated meta
      analysis.
AB  - STUDY OBJECTIVE: To compare intra-articular lidocaine (IAL) with intravenous
      analgesia and sedation (IVAS) for manual closed reduction of acute anterior
      shoulder dislocation. DESIGN: Meta-analysis. SETTING: Metropolitan medical
      university. MEASUREMENTS: A literature search was conducted of PubMed, Ovid and
      Cochrane Library, to identify randomized controlled trials (RCTs) published from
      January 1, 1990 to September 1, 2012, that compared IAL with IVAS for manual
      closed reduction of acute anterior shoulder dislocation. Effective data were
      pooled using fixed-effects or random-effects models with mean differences (MDs)
      and risk ratios (RRs) for continuous and dichotomous variables, respectively.
      MAIN RESULTS: Nine RCTs comprising 438 patients were analyzed. Statistical
      analyses showed that IAL was superior to IVAS with respect to lower complication
      risk (P < 0.00001) and shorter mean hospital length of stay (P = 0.03). No
      significant differences were noted in success of joint reduction (P = 0.16),
      patient satisfaction (P = 0.12), or postreduction pain relief (P = 0.76).
      However, IAL required more time than IVAS from injection to reduction (P <
      0.00001). Subgroup analyses showed that IVAS was associated with higher risks of
      respiratory depression (P < 0.0001), vomiting (P = 0.04), and thrombophlebitis (P
      = 0.008), but no statistical differences were identified in nausea (P = 0.06),
      hypotension (P = 0.10), drowsiness (P = 0.45), or headache (P = 0.29).
      CONCLUSIONS: Intra-articular lidocaine injection may be safer than IVAS because
      there are fewer risks of postoperative complications with IAL. Both techniques
      are similarly effective for manual closed reduction of acute anterior shoulder
      dislocation.

PMID- 25066880
TI  - 'She called her partner - hence she is needy': depressed patients show increased
      tendencies to make spontaneous trait inferences.
AB  - BACKGROUND: Interpersonal stress generation is an important maintaining factor in
      major depression; however, little is known about the psychological mechanisms
      that undermine interpersonal functioning. This study investigated the role of
      deficits in person perception to this regard. METHOD: Depressed patients (n = 20)
      and healthy controls (n = 20) completed a false recognition task that measured
      participants' tendencies to make spontaneous trait inferences (STIs), that is to
      spontaneously ascribe personality traits to other people. Participants then
      reported interpersonal daily hassles for one week following the task. RESULTS:
      Tendencies to make STIs were significantly higher in depressed patients,
      particularly those with a history of childhood trauma. The degree to which
      participants made STIs was significantly related to depression severity, and
      predicted the occurrence of interpersonal daily hassles during follow-up across,
      but not within groups. CONCLUSIONS: The results suggest that depressed patients
      show characteristic biases in person perception that may contribute to the
      generation of interpersonal stress.

PMID- 25066878
TI  - Amusia and protolanguage impairments in schizophrenia.
AB  - BACKGROUND: Both language and music are thought to have evolved from a musical
      protolanguage that communicated social information, including emotion.
      Individuals with perceptual music disorders (amusia) show deficits in auditory
      emotion recognition (AER). Although auditory perceptual deficits have been
      studied in schizophrenia, their relationship with musical/protolinguistic
      competence has not previously been assessed. METHOD: Musical ability was assessed
      in 31 schizophrenia/schizo-affective patients and 44 healthy controls using the
      Montreal Battery for Evaluation of Amusia (MBEA). AER was assessed using a novel
      battery in which actors provided portrayals of five separate emotions. The
      Disorganization factor of the Positive and Negative Syndrome Scale (PANSS) was
      used as a proxy for language/thought disorder and the MATRICS Consensus Cognitive
      Battery (MCCB) was used to assess cognition. RESULTS: Highly significant deficits
      were seen between patients and controls across auditory tasks (p < 0.001).
      Moreover, significant differences were seen in AER between the amusia and intact
      music-perceiving groups, which remained significant after controlling for group
      status and education. Correlations with AER were specific to the melody domain,
      and correlations between protolanguage (melody domain) and language were
      independent of overall cognition. DISCUSSION: This is the first study to document
      a specific relationship between amusia, AER and thought disorder, suggesting a
      shared linguistic/protolinguistic impairment. Once amusia was considered, other
      cognitive factors were no longer significant predictors of AER, suggesting that
      musical ability in general and melodic discrimination ability in particular may
      be crucial targets for treatment development and cognitive remediation in
      schizophrenia.

PMID- 25066881
TI  - The evolution of environmental tolerance and range size: a comparison of
      geographically restricted and widespread Mimulus.
AB  - The geographic ranges of closely related species can vary dramatically, yet we do
      not fully grasp the mechanisms underlying such variation. The niche breadth
      hypothesis posits that species that have evolved broad environmental tolerances
      can achieve larger geographic ranges than species with narrow environmental
      tolerances. In turn, plasticity and genetic variation in ecologically important
      traits and adaptation to environmentally variable areas can facilitate the
      evolution of broad environmental tolerance. We used five pairs of western North
      American monkeyflowers to experimentally test these ideas by quantifying
      performance across eight temperature regimes. In four species pairs, species with
      broader thermal tolerances had larger geographic ranges, supporting the niche
      breadth hypothesis. As predicted, species with broader thermal tolerances also
      had more within-population genetic variation in thermal reaction norms and
      experienced greater thermal variation across their geographic ranges than species
      with narrow thermal tolerances. Species with narrow thermal tolerance may be
      particularly vulnerable to changing climatic conditions due to lack of plasticity
      and insufficient genetic variation to respond to novel selection pressures.
      Conversely, species experiencing high variation in temperature across their
      ranges may be buffered against extinction due to climatic changes because they
      have evolved tolerance to a broad range of temperatures. 

PMID- 25066882
TI  - Investigation of diversity in Aegilops biuncialis and Aegilops umbellulata by A
      PAGE.
AB  - Aegilops species, wild relatives of wheat, are one of the important genetic
      resources in wheat breeding. In this study 13 populations of Aegilops biuncialis
      along with 2 populations of progenitor species Aegilops umbellulata were analysed
      in six replications using of acid polyacrylamide gel electrophoresis. The results
      showed that TN-01-293 population had a high gluten and grind quality because of
      high percentage of gamma-45.31 and gamma-43.5 (high gluten quality index) in the
      observed band. Also, Ahar population from A. biuncialis was introduced to light
      gluten because of low percentage of gamma-45.31 and gamma-43.5 bands of quality.
      All studied populations can be used in breeding programmes for improving quality
      of bread wheat because of lack of gamma-42 and gamma-40 bands (low quality
      indices) and including high frequency of band in omega region. Through using
      PopGen 1.32 software, diversity is estimated . The maximum value of genetic
      diversity among populations resulted 49%. 

PMID- 25066883
TI  - Human herpesvirus 6 can be detected in cerebrospinal fluid without associated
      symptoms after allogeneic hematopoietic cell transplantation.
AB  - BACKGROUND: Human herpesvirus 6 (HHV-6) is an opportunistic pathogen after
      hematopoietic cell transplantation (HCT) that is associated with central nervous
      system (CNS) dysfunction. OBJECTIVES: The aim of this study was to determine the
      frequency and significance of HHV-6 DNA detection in cerebrospinal fluid (CSF)
      after HCT. STUDY DESIGN: We identified patients with HHV-6 DNA in CSF using
      quantitative PCR. Patients with neurologic symptoms and HHV-6 DNA in CSF without
      identification of an alternative etiology were categorized as having HHV-6 CNS
      dysfunction. RESULTS: Among 3902 allogeneic HCT recipients from 1998 to 2012, 51
      of 124 tested patients had HHV-6 DNA in CSF; 37 met criteria for HHV-6 CNS
      dysfunction and 14 (27%) did not. Patients with an alternative diagnosis had
      longer time to HHV-6 detection and lower viral load in CSF. Six patients without
      HHV-6 CNS dysfunction were not treated and had no morbidity attributable to HHV
      6. Kaplan-Meier analysis demonstrated poor overall survival among all patients.
      Variables associated with higher all-cause mortality in a multivariable Cox model
      included alternative diagnosis (adjusted hazard ratio [aHR], 8.4; 95% CI, 1.7
      40.9; P = 0.009) and higher peak plasma viral load (log(10) scale) (aHR, 1.4; 95%
      CI, 1.1-1.9; P = 0.01). CONCLUSION: We identified a number of allogeneic HCT
      recipients with HHV-6 DNA in CSF who did not meet criteria for HHV-6 CNS
      dysfunction. All patients had poor survival. Whether CSF HHV-6 DNA detection in
      patients without associated CNS dysfunction independently contributes to
      mortality and warrants treatment is unclear; management of these patients
      warrants further investigation.

PMID- 25066885
TI  - Reference panel of cloned HIV-2 plasmid DNA for nucleic acid assay development,
      evaluation, and quality monitoring.
AB  - BACKGROUND: Currently, no FDA-approved HIV-2 nucleic acid assay is commercially
      available in the United States, although several laboratories have developed in
      house assays to confirm HIV-2 infections. A major limitation in the development
      of novel HIV-2 diagnostic assays is the lack of reference materials that can be
      used to evaluate, optimize, and monitor assay performance. STUDY DESIGN: Eleven
      viral stocks of HIV-2 isolates from various West African countries, including the
      Ivory Coast, Senegal, and Guinea-Bissau, were used to clone the entire LTR and
      pol regions from each virus. RESULTS: We successfully cloned, sequenced, and
      group classified 22 HIV-2 DNA plasmids including 11 full length LTR (~849 bp) and
      11 pol (~2995 bp) sequences. There were eight HIV-2 group A and three group B in
      both the LTR and pol regions. CONCLUSIONS: This reference panel provides a
      robust, quantifiable, renewable, and non-infectious set of reagents that can be
      used for the development and evaluation of new HIV-2 molecular diagnostic assays
      and quality assurance and quality control reagents for use in the clinical
      laboratories.

PMID- 25066884
TI  - Molecular epidemiology of hepatitis B virus in Cordoba, Argentina.
AB  - BACKGROUND: The analysis of the genomes of hepatitis B virus (HBV) identifies
      phylogenetic variants called genotypes, which may lead to distinct biological and
      clinical behaviors. OBJECTIVES: The aim of this study was to describe the current
      molecular epidemiology and genetic diversity of HBV in Cordoba, Argentina. STUDY
      DESIGN: A total of 52 HBV samples, 40 from HBV mono-infected and 12 from human
      immunodeficiency virus (HIV)-HBV co-infected patients, were sequenced in the S
      gene and in the basal core promoter-precore (BCP-pC) region. RESULTS: Presence of
      subgenotypes F1b (35%) and F4 (17.5%), subgenotype A2 (37.5%), C (5.0%)
      (subgenotype could not be defined) and D (5.0%) (subgenotype D2, and the other
      could not be defined) were observed among mono-infected patients. The co-infected
      individuals displayed a different genotype distribution: sub-genotype A2 was the
      most common (75.0%), followed by subgenotype F1b (25.0%). CONCLUSIONS: These
      results showed two epidemiologic scenarios: the mono-infected population may
      represent the ethnic composition of the current human population of Cordoba,
      where the Amerindian (genotype F) and European origins (subgenotype A2) account
      for the 90% of the samples; for the co-infected patients, the high prevalence of
      subgenotype A2 resemble previous analyses from Buenos Aires. In addition,
      mutations in hepatitis B surface antigen (HBsAg), polymerase and BCP-pC regions
      were identified, mainly in chronic or co-infected patients.

PMID- 25066887
TI  - Catalytic processes that changed the world: 100 years Max-Planck-Institut fur
      Kohlenforschung.

PMID- 25066886
TI  - The relevance of respiratory viral infections in the exacerbations of chronic
      obstructive pulmonary disease-a systematic review.
AB  - BACKGROUND: Despite the increasing knowledge on the role of viruses in
      exacerbations of COPD (AECOPD), it is less clear which viruses are involved and
      to what extent they contribute to exacerbations. This review aims to
      systematically combine and evaluate the available literature of the prevalence of
      respiratory viruses in patients with AECOPD, detected by PCR. METHODS: An
      electronic search strategy was performed on PubMed and Embase and reference lists
      were screened for eligible studies. Cross-sectional, prospective studies and case
      control studies were included. The primary outcome measure was the prevalence of
      respiratory viruses (adenovirus, bocavirus, coronavirus, EBV, hMPV, influenza,
      parainfluenza, rhino-/enterovirus, RSV) in respiratory secretions of patients
      during an AECOPD. Secondary outcomes were the odds of the presence of the viruses
      in different respiratory secretions and the odds of the presence of viruses in
      upper and lower respiratory tract (URT/LRT) samples. RESULTS: Nineteen studies
      with 1728 patients were included. Rhino-/enteroviruses (16.39%), RSV (9.90%) and
      influenza (7.83%) were the most prevalent viruses detected with lower detection
      rates of coronaviruses (4.08%) and parainfluenza (3.35%). Adenovirus (2.07%),
      hMPV (2.78%) and bocaviruses (0.56%) appear to be rare causative agents of
      AECOPD. Definitive conclusions regarding the role of EBV cannot be made. Seven of
      the eight analyzed viruses had a higher prevalence in LRT samples. Coronaviruses
      were detected more frequently in the URT. CONCLUSIONS: Respiratory viruses are
      frequently detected in both URT and LRT samples in AECOPD with rhino
      /enteroviruses, RSV and influenza viruses the most prevalent viruses. Detection
      rates vary between the two sites for different viruses.

PMID- 25066888
TI  - A row-column addressed micromachined ultrasonic transducer array for surface
      scanning applications.
AB  - Row-column addressed arrays for ultrasonic non-destructive testing (NDT)
      applications are analyzed and demonstrated in this paper. Simulation and
      experimental results of a row-column addressed 32 by 32 capacitive micromachined
      ultrasonic transducer (CMUT) array are presented. The CMUT array, which was
      designed for medical imaging applications, has a center frequency of 5.3MHz. The
      CMUT array was used to perform C-scans on test objects with holes that have
      diameters of 1.0mm and 0.5mm. The array transducer has an aperture size of 4.8mm
      by 4.8mm, and it was used to scan an area of 4.0mm by 4.0mm. Compared to an N by
      N fully addressed 2-D array, a row-column addressed array of the same number of
      elements requires fewer (N instead of N(2)) pairs of interconnection and
      supporting electronic components such as pulsers and amplifiers. Even though the
      resulting field of view is limit by the aperture size, row-column addressed
      arrays and the row-column addressing scheme can be an alternative option of 2-D
      arrays for NDT applications. 

PMID- 25066889
TI  - Ultrasound generation with high power and coil only EMAT concepts.
AB  - Electro-magnetic acoustic transducers (EMATs) are intended as non-contact and non
      destructive ultrasound transducers for metallic material. The transmitted
      intensities from EMATS are modest, particularly at notable lift off distances.
      Some time ago a concept for a "coil only EMAT" was presented, without static
      magnetic field. In this contribution, such compact "coil only EMATs" with
      effective areas of 1-5cm(2) were driven to excessive power levels at MHz
      frequencies, using pulsed power technologies. RF induction currents of 10kA and
      tens of Megawatts are applied. With increasing power the electroacoustic
      conversion efficiency also increases. The total effect is of second order or
      quadratic, therefore non-linear and progressive, and yields strong ultrasound
      signals up to kW/cm(2) at MHz frequencies in the metal. Even at considerable lift
      off distances (cm) the ultrasound can be readily detected. Test materials are
      aluminum, ferromagnetic steel and stainless steel (non-ferromagnetic). Thereby,
      most metal types are represented. The technique is compared experimentally with
      other non-contact methods: laser pulse induced ultrasound and spark induced
      ultrasound, both damaging to the test object's surface. At small lift off
      distances, the intensity from this EMAT concept clearly outperforms the laser
      pulses or heavy spark impacts. 

PMID- 25066890
TI  - It is better to smile to women: gender modifies perception of honesty of smiling
      individuals across cultures.
AB  - Social perception studies have revealed that smiling individuals are perceived
      more favourably on many communion dimensions in comparison to nonsmiling
      individuals. Research on gender differences in smiling habits showed that women
      smile more than men. In our study, we investigated this phenomena further and
      hypothesised that women perceive smiling individuals as more honest than men. An
      experiment conducted in seven countries (China, Germany, Mexico, Norway, Poland,
      Republic of South Africa and USA) revealed that gender may influence the
      perception of honesty in smiling individuals. We compared ratings of honesty made
      by male and female participants who viewed photos of smiling and nonsmiling
      people. While men and women did not differ on ratings of honesty in nonsmiling
      individuals, women assessed smiling individuals as more honest than men did. We
      discuss these results from a social norms perspective. 

PMID- 25066891
TI  - Deliberate self-harm and suicidal ideation among male Iraq/Afghanistan-era
      veterans seeking treatment for PTSD.
AB  - The objectives of the present research were to examine the prevalence of
      deliberate self-harm (DSH) among 214 U.S. male Iraq/Afghanistan-era veterans
      seeking treatment for posttraumatic stress disorder (PTSD) and to evaluate the
      relationship between DSH and suicidal ideation within this population.
      Approximately 56.5% (n = 121) reported engaging in DSH during their lifetime;
      45.3% (n = 97) reported engaging in DSH during the previous 2 weeks. As
      hypothesized, DSH was a significant correlate of suicidal ideation among male
      Iraq/Afghanistan-era veterans, OR = 3.88, p < .001, along with PTSD symptom
      severity, OR = 1.03, p < .001, and combat exposure, OR = 0.96, p = .040. A follow
      up analysis identified burning oneself, OR = 17.14, p = .017, and hitting
      oneself, OR = 7.93, p < .001, as the specific DSH behaviors most strongly
      associated with suicidal ideation. Taken together, these findings suggest that
      DSH is quite prevalent among male Iraq/Afghanistan-era veterans seeking treatment
      for PTSD and is associated with increased risk for suicidal ideation within this
      population. Routine assessment of DSH is recommended when working with male
      Iraq/Afghanistan veterans seeking treatment for PTSD. 

PMID- 25066892
TI  - Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR- and
      BECLIN1-complex.
AB  - Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for
      Delta-9-Tetrahydrocannabinol in the central nervous system (CNS), mediating
      retrograde synaptic signaling of the endocannabinoid system. Beside its
      expression in various CNS regions, CB1 is ubiquituous in peripheral tissues,
      where it mediates, among other activities, the cell's energy homeostasis. We
      sought to examine the role of CB1 in the context of the evolutionarily conserved
      autophagic machinery, a main constituent of the regulation of the intracellular
      energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an
      elevated autophagic flux, while the expression of autophagy-related genes
      remained unaltered. Pharmacological inhibition of CB1 activity using Rimonabant
      likewise caused an elevated autophagic flux, which was independent of the
      mammalian target of rapamycin complex 1, a major switch in the control of
      canonical autophagy. In addition, knocking down coiled-coil myosin-like BCL2
      interacting protein 1, the key-protein of the second canonical autophagy control
      complex, was insufficient to reduce the elevated autophagic flux induced by
      Rimonabant. Interestingly, lysosomal activity is not altered, suggesting a
      specific effect of CB1 on the regulation of autophagic flux. We conclude that CB1
      activity affects the autophagic flux independently of the two major canonic
      regulation complexes controlling autophagic vesicle formation. Regulation of the
      autophagic flux in certain physiological situations such as an imbalance of
      nutrient supply as well as in pathological stages is of major importance for
      neuronal and non-neuronal cells. CB1 (Cannabinoid receptor 1) affects the
      metabolism of cells directly. In this study, we provide evidence that CB1
      signaling has a direct influence on autophagy which might help the cell to find
      the right adjustment to different metabolic states and CB1 activity exerts its
      modulatory action independent of the canonical mTOR- and BECLIN1-complexes
      regulating autophagy. 

PMID- 25066893
TI  - Successful haematopoietic stem cell transplantation in 44 children from healthy
      siblings conceived after preimplantation HLA matching.
AB  - Haematopoietic stem cell transplantation (HSCT) remains the best therapeutic
      option for many acquired and inherited paediatric haematological disorders.
      Unfortunately, the probability of finding an HLA matched donor is limited. An
      alternative technique is PGD combined with HLA matching, which offers the
      possibility of selecting unaffected embryos that are HLA compatible with the sick
      child, with the aim of possible use of stem cells from the resulting baby in
      future. Since the first successful report for Fanconi anaemia a decade ago, the
      therapeutic success of this technique was reported in a few cases and for a
      limited number of disorders. Here, we report full recovery of 44 sick children
      who received HSCT from healthy infants conceived after pre-implantation HLA
      matching for the following 10 indications; beta-thalassaemia, Wiskott-Aldrich
      syndrome, Fanconi anaemia, sickle cell anaemia, acute myeloid leukaemia, acute
      lymphoblastic leukaemia, Glanzmann's thrombasthaenia, Diamond-Blackfan anaemia, X
      linked adrenoleukodystrophy and mucopolysaccharidosis type I. No serious
      complications were observed among recipients and donors. Graft failure occurred
      in four children with beta-thalassaemia where a second HSCT was planned.
      Preimplantation HLA matching is a reliable technique and provides a realistic
      option for couples seeking treatment for an affected child when no HLA-matched
      donor is available. 

PMID- 25066894
TI  - Ionic field effect and memristive phenomena in single-point ferroelectric domain
      switching.
AB  - Electric field-induced polarization switching underpins most functional
      applications of ferroelectric materials in information technology, materials
      science and optoelectronics. Recently, much attention has been focused on the
      switching of individual domains using scanning probe microscopy. The classical
      picture of tip-induced switching, including formation of cylindrical domains with
      size, is largely determined by the field distribution and domain wall motion
      kinetics. The polarization screening is recognized as a necessary precondition to
      the stability of ferroelectric phase; however, screening processes are generally
      considered to be uniformly efficient and not leading to changes in switching
      behaviour. Here we demonstrate that single-point tip-induced polarization
      switching can give rise to a surprisingly broad range of domain morphologies,
      including radial and angular instabilities. These behaviours are traced to the
      surface screening charge dynamics, which in some cases can even give rise to
      anomalous switching against the electric field (ionic field effect). 

PMID- 25066895
TI  - Individualised care for women with assisted conception pregnancies and midwifery
      practice implications: An analysis of the existing research and current practice.
AB  - OBJECTIVE: the aim is to explore the psychosocial needs of women who are pregnant
      after assisted conception, specifically in vitro Fertilisation and whether their
      needs are being addressed within the current maternity care service. DESIGN:
      critical review of the literature using a narrative approach. FINDINGS AND KEY
      CONCLUSIONS: 15 papers were identified. These included both qualitative and
      quantitative studies, literature reviews and surveys. The findings of this
      limited narrative review imply that women who undergo assistive reproductive
      techniques to achieve pregnancy have higher levels of anxiety in pregnancy and
      may have some difficulties in the transition to parenthood leading to perinatal
      morbidity. It appears that for this group of women it is important that their
      history in achieving pregnancy is known to the care providers, to enable the
      alleviation of some of the anxieties they face. Various aspects of antenatal care
      have been identified as possible areas which if addressed may reduce these levels
      of anxiety leading to a reduction in perinatal morbidity. IMPLICATIONS FOR
      PRACTICE: currently, there is insufficient evidence to suggest that providing
      specialist midwifery care reduces morbidity in these women. However, maternity
      service providers should consider offering additional antenatal and postnatal
      services to meet the needs of this group in advance of further research in this
      area.

PMID- 25066896
TI  - A simple method to disentangle nanoparticle optical properties by darkfield
      microspectroscopy.
AB  - We present a darkfield optical microspectroscopy technique devoted to the
      disentangled measurement of the absorption and scattering cross sections of
      nanoparticle (NP) samples with variable concentration. The robustness of the
      method, including the needed instrumental calibrations, is examined in detail by
      analyzing and quantifying the major sources of statistic and systematic errors.
      As an exemplary case, results are presented on a gold NP colloid. The technique
      takes advantage of a simple inverted microscope, coupled with a spectrograph and
      equipped with a darkfield condenser and a variable numerical aperture objective
      to obtain spectra either in darkfield or brightfield optical configurations. By
      adopting the Lambert-Beer (LB) equation modeling, we were able to disentangle and
      measure with a single setup the absorption, scattering, and extinction
      coefficients of the same sample by combining three spectra, obtained by
      opportunely varying the objective numerical aperture. Typical plasmonic
      resonances were recognized at approximately 520 and 750 nm. Optical coefficients
      were measured as a function of particle number density (0.04-3.94 um(-3),
      corresponding to 40 uM-4 mM nominal Au concentration) and good linearity was
      verified up to ~1.5 um(-3) (~1 mM Au). Moreover, extinction and scattering cross
      sections were quantified and the validity of the LB approximation was reviewed.
      Besides its applications to plasmonic NPs, this method may be appropriate for any
      colloid, provided there exists a characteristic spectral feature in the
      ultraviolet-visible-near infrared range. This technique may be exploited to
      localize NPs in biological samples.

PMID- 25066897
TI  - A role for arginine-12 in thrombin-thrombomodulin-mediated activation of thrombin
      activatable fibrinolysis inhibitor.
AB  - BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a proenzyme
      that links coagulation and fibrinolysis. TAFI can be activated by thrombin, the
      thrombin-thrombomodulin complex and plasmin through cleavage of the first 92
      amino acids from the enzyme. In silico analysis of the TAFI sequence revealed a
      potential thrombin cleavage site at Arg12. The aim of this study was to determine
      whether TAFI can be cleaved at Arg12 and whether this cleavage plays a role in
      TAFI activation. METHODS: A peptide based on the first 18 amino acids of TAFI was
      used to determine whether thrombin was able to cleave at Arg12. Mass spectrometry
      was performed to determine whether the Arg12-cleaved peptide was released from
      full-length TAFI. Furthermore, a TAFI mutant in which Arg12 was replaced by a
      glutamine (TAFI-R12Q) was constructed and characterized with respect to its
      activation kinetics. RESULTS: The peptide and mass spectrometry data showed that
      thrombin was able to cleave TAFI at Arg12, but with low efficiency in full-length
      TAFI. Characterization of TAFI-R12Q showed no difference in thrombin-mediated
      activation from wild-type TAFI. However, there was an approximately 60-fold
      impairment in activation of TAFI-R12Q by the thrombin-thrombomodulin complex.
      CONCLUSIONS: Arg12 of TAFI plays an important role in thrombomodulin-mediated
      TAFI activation by thrombin. Thrombin is able to cleave TAFI at Arg12, but it
      remains to be determined whether Arg12 is part of an exosite for thrombomodulin
      or whether cleavage at Arg12 accelerates thrombomodulin-mediated TAFI activation.

PMID- 25066898
TI  - Blood groups and human groups: collecting and calibrating genetic data after
      World War Two.
AB  - Arthur Mourant's The Distribution of the Human Blood Groups (1954) was an
      "indispensable" reference book on the "anthropology of blood groups" containing a
      vast collection of human genetic data. It was based on the results of blood
      grouping tests carried out on half-a-million people and drew together studies on
      diverse populations around the world: from rural communities, to religious
      exiles, to volunteer transfusion donors. This paper pieces together sequential
      stages in the production of a small fraction of the blood-group data in Mourant's
      book, to examine how he and his colleagues made genetic data from people. Using
      sources from several collecting projects, I follow how blood was encountered, how
      it was inscribed, and how it was turned into a laboratory resource. I trace
      Mourant's analytical and representational strategies to make blood groups both
      credibly 'genetic' and understood as relevant to human ancestry, race and
      history. In this story, 'populations' were not simply given, but were produced
      through public health, colonial and post-colonial institutions, and by the labour
      and expertise of subjects, assistants and mediators. Genetic data were not self
      evidently 'biological', but were shaped by existing historical and geographical
      identities, by political relationships, and by notions of kinship and belonging. 

PMID- 25066899
TI  - Unfolding epidemiological stories: how the WHO made frozen blood into a flexible
      resource for the future.
AB  - In the decades after World War II, the World Health Organization (WHO) played an
      important role in managing the process of stabilizing collections of variable
      blood samples as a fundamentally unstable, protean, and unfolding biomedical
      resource. In this system, known and as yet unknown constituents of blood were
      positioned as relevant to the work of multiple constituencies including human
      population geneticists, physical anthropologists, and immunologists. To
      facilitate serving these and other constituencies, it was crucial to standardize
      practices of collecting and preserving samples of blood from globally distributed
      human populations. The WHO achieved this by linking its administrative
      infrastructure-comprised of expert advisory groups and technical reports-to key
      laboratories, which served as sites for demonstrating and also for disseminating
      standards for working with variable blood samples. The practices that were
      articulated in making blood samples into a flexible resource contributes to
      emerging histories of global health that highlight the centrality of new
      institutions, like the WHO, new forms of expertise, like population genetics and
      serological epidemiology, and new kinds of research materials, like frozen blood.

PMID- 25066900
TI  - Pain, motor function and health-related quality of life in children with cerebral
      palsy as reported by their physiotherapists.
AB  - BACKGROUND: Children and adolescents with cerebral palsy suffer from higher
      levels of pain than their peers without disability. The aim of this study was to
      explore the impact of pain on health-related quality of life and motor function
      in individuals with cerebral palsy as reported by health professionals. METHODS:
      Cross-sectional study carried out in Associations for Care of Individuals with
      Cerebral Palsy and Related Disabilities (ASPACE) in Balearic Islands and Castile
      Leon (Spain). Thirty-five physiotherapists rated pain, health-related quality of
      life and motor function in 91 children and adolescents with cerebral palsy [8
      19y]. A semi-structured interview was used to collect demographic and clinical
      data according with the Study of Participation of Children with Cerebral Palsy
      Living in Europe (SPARCLE). RESULTS: Physiotherapists reported that 51% of
      individuals with cerebral palsy suffered from pain. Physiotherapists also
      perceived that pain in individuals with cerebral palsy was responsible for
      reductions of psychological but not physical domains of health-related quality of
      life. According with physiotherapists' estimations, motor impairment scores were
      not correlated with pain scores in individuals with cerebral palsy, but they were
      significantly associated with physical and autonomy domains of health-related
      quality of life. CONCLUSIONS: These findings highlighted the importance of
      assessing and providing interventions for pain relief in persons with cerebral
      palsy even at an early age.

PMID- 25066901
TI  - Engineered electron-transfer chain in photosystem 1 based photocathodes
      outperforms electron-transfer rates in natural photosynthesis.
AB  - Photosystem 1 (PS1) triggers the most energetic light-induced charge-separation
      step in nature and the in vivo electron-transfer rates approach 50 e(-)  s(-1) 
      PS1(-1). Photoelectrochemical devices based on this building block have to date
      underperformed with respect to their semiconductor counterparts or to natural
      photosynthesis in terms of electron-transfer rates. We present a rational design
      of a redox hydrogel film to contact PS1 to an electrode for photocurrent
      generation. We exploit the pH-dependent properties of a poly(vinyl)imidazole
      Os(bispyridine)2Cl polymer to tune the redox hydrogel film for maximum electron
      transfer rates under optimal conditions for PS1 activity. The PS1-containing
      redox hydrogel film displays electron-transfer rates of up to 335+/-14 e(-)  s(
      1)  PS1(-1), which considerably exceeds the rates observed in natural
      photosynthesis or in other semiartificial systems. Under O2 supersaturation,
      photocurrents of 322+/-19 MUA cm(-2) were achieved. The photocurrents are only
      limited by mass transport of the terminal electron acceptor (O2). This implies
      that even higher electron-transfer rates may be achieved with PS1-based systems
      in general.

PMID- 25066902
TI  - Nitrogen removal from medium-age landfill leachate via post-denitrification
      driven by PHAs and glycogen in a single sequencing batch reactor.
AB  - An anaerobic/aerobic/anoxic (AOA) process in a sequencing batch reactor (SBR) was
      proposed to treat typical medium-age landfill leachate without extra carbon
      addition. In a steady-state, the average removal efficiencies of NH4(+)-N, total
      nitrogen (TN) and COD were 99.7 +/- 0.1%, 98.3 +/- 0.3% and 89.8 +/- 1.4%, when
      influent NH4(+)-N, TN and COD were 1025-1327 mg/L, 1346-1854 mg/L and 6430-9372
      mg/L, respectively. In the anaerobic stage, dissolved organic matter was taken up
      partially and stored as polyhydroxyalkanoates (PHAs) with concomitant consumption
      of glycogen. In the aerobic stage, PHAs was oxidized and glycogen was replenished
      in the bacterial cells, when TN of 75.4 mg/L was removed via simultaneous
      nitrification and denitrification (SND). The residual nitrate and nitrite were
      denitrified completely by utilizing residual PHAs and glycogen as electron donors
      in the anoxic phase. Denitrifying glycogen accumulating organisms (GAOs) were
      considered to be playing the major role in the process.

PMID- 25066903
TI  - Electroporation of Chlorella vulgaris to enhance biomethane production.
AB  - This research investigated the feasibility of using electroporation (EP) as a
      pretreatment method for algal biomass used as feedstock for anaerobic digestion.
      The results showed that pretreating algal biomass with EP significantly improved
      the soluble COD (SCOD), increasing it to more than 830% at 28 kWh/m(3) treatment
      intensity (TI). Besides TI, culture conditions also affected the performance of
      the EP process. On the basis of SCOD, a sample pH of 7.0 and cell concentration
      of 13.2g/L were found to be optimal for the EP process. Despite a direct
      relationship between TI and ionic strength (IS), SCOD decreased with increasing
      IS. At 35 kWh/m(3) TI, bio-CH4 production increased by as high as 110%. It was
      also observed that lower TI levels resulted in high rates of gain per energy
      input compared to higher degrees of treatment.

PMID- 25066904
TI  - Survival analysis for valproic acid use in adult glioblastoma multiforme: a meta
      analysis of individual patient data and a systematic review.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is the most lethal type of primary brain
      tumor, and patients that undergo the maximum tumor resection that is safely
      possible and standard radiochemotherapy only achieve a median survival time of
      14.6 months. Several clinical studies have reported that valproic acid could
      prolong survival of GBM patients. However, the results of these studies are
      inconsistent. We examined relevant studies and conducted a meta-analysis to
      assess the effects of VPA on survival times and recurrence. METHODS: A
      bibliographic search was performed in the EMBASE, MEDLINE, ClinicalTrials.gov and
      Cochrane Central Register of the Controlled Trials databases to identify
      potentially relevant articles or conference abstracts that investigated the
      effects of VPA on the outcome of glioma patients. Five observational studies were
      included. RESULTS: Pooled estimates of the hazard ratio (HR) and 95% confidence
      intervals (CI) were calculated. Our meta-analysis confirmed the benefit of using
      VPA (HR, 0.56; 95% CI, 0.44-0.71). Sub-group analysis shows that patients treated
      with VPA had a hazard ratio of 0.74 with a 95% confidence interval of 0.59-0.94
      vs. patients treated by other-AEDs and a hazard ratio of 0.66 with a 95%
      confidence interval of 0.52-0.84 vs. patients treated by administration of non
      AEDs. No heterogeneity was observed in the subset analysis. CONCLUSION: The
      results of our study suggest that glioblastoma patients may experience prolonged
      survival due to VPA administration. Sub-analysis confirmed the benefit of VPA use
      compared to a non-AEDs group and an other-AEDs group. Further RCTs of this
      subject should be performed.

PMID- 25066905
TI  - Tris buffer modulates polydopamine growth, aggregation, and paramagnetic
      properties.
AB  - Despite the growing technological interest of polydopamine (dopamine melanin)
      based coatings for a broad variety of applications, the factors governing
      particle size, shape, and electronic properties of this bioinspired
      multifunctional material have remained little understood. Herein, we report a
      detailed characterization of polydopamine growth, particle morphology, and
      paramagnetic properties as a function of dopamine concentration and nature of the
      buffer (pH 8.5). Dynamic Light Scattering data revealed an increase in the
      hydrodynamic radii (Rh) of melanin particles with increasing dopamine
      concentration in all buffers examined, especially in phosphate buffer.
      Conversely, a marked inhibition of particle growth was apparent in Tris buffer,
      with Rh remaining as low as <100 nm during polymerization of 0.5 mM dopamine.
      Small angle neutron scattering data suggested formation of bidimensional
      structures in phosphate or bicarbonate buffers, while apparently three
      dimensional fractal objects prevailed in Tris buffer. Finally, electron
      paramagnetic resonance spectra revealed a broader signal amplitude with a
      peculiar power saturation decay profile for polydopamine samples prepared in Tris
      buffer, denoting more homogeneous paramagnetic centers with respect to similar
      samples obtained in phosphate and bicarbonate buffers. Overall, these results
      disclose Tris buffer as an efficient modulator of polydopamine buildup and
      properties for the rational control and fine-tuning of melanin aggregate size,
      morphology, and free radical behavior. 

PMID- 25066906
TI  - Tracheal laceration as a complication of out-of-hospital emergency tracheal
      intubation in a patient with COPD.
AB  - Tracheobronchial injuries related to emergency endotracheal intubations are
      reported to be associated with an increased risk of mortality. Many mechanical
      risk factors may become more frequent in an emergency setting leading to such
      injuries. Aside from these factors that may complicate endotracheal intubation,
      this procedure is not recommended a priori for ventilation due to the resulting
      interruptions in external chest compressions, by 2010 cardiopulmonary
      resuscitation (CPR) and external chest compression guidelines. We present a 78
      year-old woman with known chronic obstructive pulmonary disease who had a
      tracheal laceration after emergency endotracheal intubation during CPR. Thorax
      computed tomography revealed an overinflated tube cuff. The trachea was repaired
      surgically; however, our patient died on the fourth postoperative day due to
      multiple-organ failure. Prehospital providers must remain especially vigilant to
      priorities in airway management during CPR and aware of the dangers associated
      with field tracheal intubation under less than ideal conditions.

PMID- 25066907
TI  - The possibility of application of spiral brain computed tomography to traumatic
      brain injury.
AB  - OBJECTIVES: The spiral computed tomography (CT) with the advantage of low
      radiation dose, shorter test time required, and its multidimensional
      reconstruction is accepted as an essential diagnostic method for evaluating the
      degree of injury in severe trauma patients and establishment of therapeutic
      plans. However, conventional sequential CT is preferred for the evaluation of
      traumatic brain injury (TBI) over spiral CT due to image noise and artifact. We
      aimed to compare the diagnostic power of spiral facial CT for TBI to that of
      conventional sequential brain CT. METHODS: We evaluated retrospectively the
      images of 315 traumatized patients who underwent both brain CT and facial CT
      simultaneously. The hemorrhagic traumatic brain injuries such as epidural
      hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, and contusional
      hemorrhage were evaluated in both images. Statistics were performed using Cohen's
      kappa to compare the agreement between 2 imaging modalities and sensitivity,
      specificity, positive predictive value, and negative predictive value of spiral
      facial CT to conventional sequential brain CT. RESULTS: Almost perfect agreement
      was noted regarding hemorrhagic traumatic brain injuries between spiral facial CT
      and conventional sequential brain CT (Cohen's kappa coefficient, 0.912). To
      conventional sequential brain CT, sensitivity, specificity, positive predictive
      value, and negative predictive value of spiral facial CT were 92.2%, 98.1%,
      95.9%, and 96.3%, respectively. CONCLUSION: In TBI, the diagnostic power of
      spiral facial CT was equal to that of conventional sequential brain CT.
      Therefore, expanded spiral facial CT covering whole frontal lobe can be applied
      to evaluate TBI in the future.

PMID- 25066908
TI  - Disparities in bystander CPR provision and survival from out-of-hospital cardiac
      arrest according to neighborhood ethnicity.
AB  - STUDY OBJECTIVE: We aimed to determine if there are differences in bystander
      cardiopulmonary resuscitation (BCPR) provision and survival to hospital discharge
      from out-of-hospital cardiac arrest (OHCA) occurring in Hispanic neighborhoods in
      Arizona. METHODS: We analyzed a prospectively collected, statewide Utstein
      compliant OHCA database between January 1, 2010, and December 31, 2012. Cases of
      OHCA were geocoded to determine their census tract of event location, and their
      neighborhood main ethnicity was assigned using census data. Neighborhoods were
      classified as "Hispanic" or "non-Hispanic white" when the percentage of residents
      in the census tract was 80% or more. RESULTS: Among the 6637 geocoded adult OHCA
      victims during the study period, 4821 cases were included in this analysis, after
      excluding 1816 cases due to incident location, traumatic cause, or because the
      arrest occurred after emergency medical service arrival. In OHCAs occurring at
      Hispanic neighborhoods as compared with non-Hispanic white neighborhoods, the
      provision of BCPR (28.6% vs 43.8%; P < .001) and initially monitored shockable
      rhythm (17.3% vs 25.7%; P < .006) was significantly less frequent. Survival to
      hospital discharge was significantly lower in Hispanic neighborhoods than in non
      Hispanic white neighborhoods (4.9% vs 10.8%; P = .013). The adjusted odds ratio
      (OR) of Hispanic neighborhood for BCPR provision (OR, 0.62; 95% confidence
      interval, 0.44-0.89) was lower as compared with non-Hispanic white neighborhoods.
      CONCLUSIONS: In Arizona, OHCA patients in Hispanic neighborhoods received BCPR
      less frequently and had a lower survival to hospital discharge rate than those in
      non-Hispanic white neighborhoods. Public health efforts to attenuate this
      disparity are needed.

PMID- 25066909
TI  - Listeria meningitis-associated bradyarrhythmia treated with isoproterenol.
AB  - In the setting of increased intracranial pressure (ICP), various rhythm
      disturbances have been associated, ranging from tachyarrhythmias to
      bradyarrhythmias with atrioventricular dissociation. Although most of these
      observations have been in patients with traumatic brain injuries, it is known
      that children with acute bacterial meningitis may also have severe intracranial
      hypertension. We present the case of a previously healthy 2-year-old boy
      diagnosed with listeria meningitis. Along with clinical signs suggestive of
      increased ICP and brainstem involvement, our patient had persistent
      bradyarrhythmia with hemodynamic compromise that was refractory to epinephrine
      and successfully managed with isoproterenol.

PMID- 25066910
TI  - Emergence and resolution of the electrocardiographic spiked helmet sign in acute
      noncardiac conditions.
AB  - Patients with acute abdominal or acute thoracic events occasionally develop a
      curious electrocardiographic ST-segment elevation, where the upward shift of the
      baseline starts before the onset of the QRS complex. The shape of the complexes
      resembles a German military spiked helmet. It has been previously postulated that
      the "spiked helmet" sign is the result of an acute rise in intraabdominal or
      intrathoracic pressure causing pulsatile epidermal stretch that is in concert
      with the cardiac cycle. Here, we present 2 cases, where recognition of the spiked
      helmet sign led to immediate discovery of the underlying pathology. Removal of a
      large epigastric content resulted in the prompt resolution of the spiked helmet
      sign in the inferior leads, whereas suctioning of a large pneumothorax lead to
      the gradual disappearance of the spiked helmet sign in the chest leads. These
      cases provide the first definitive proof of a mechanical, noncardiac etiology of
      the spiked helmet sign.

PMID- 25066911
TI  - Split Ssp DnaB mini-intein-mediated production of recombinant human glucagon-like
      peptide-1/7-36.
AB  - Glucagon-like peptide-1 (GLP-1) plays an important role in the regulation of
      postprandial insulin release. Here, we used the split DnaB mini-intein system to
      produce recombinant human GLP-1/7-36 (rhGLP-1) in Escherichia coli. The C
      terminal domain of DnaB mini-intein (IntC) was genetically fused at the N
      terminus of rhGLP-1 to produce IntC-GLP-1. IntC-GLP-1 and N-terminal domain of
      DnaB mini-intein (IntN) protein were prepared in a denatured buffer of pH 8.0.
      IntC-GLP-1 was diluted 1:8 into the phosphate buffer of pH 6.6. IntN was added
      into the diluted solution of IntC-GLP-1 at the molar ratio of 1:2. Then, rhGLP-1
      was released from IntC-GLP-1 via inducible C-terminal peptide-bond cleavage by
      shifting pH from 8.0 to 6.6 at 25  degrees C for 24-H incubation. Then, the
      supernatant was applied to a Ni-Sepharose column, and the pass through fraction
      was collected. About 5.34 mg of rhGLP-1 with the purity of 97% was obtained from
      1 L of culture medium. Mass spectrometry showed the molecular weight of 3,300.45
      Da, which was equal to the theoretical value of GLP-1/7-36. The glucose-lowering
      activity of rhGLP-1 was confirmed by the glucose tolerance test in mice. In
      conclusion, the reported method was an efficient strategy to produce rhGLP-1
      without using enzyme or chemical reagents, which could also be used for other
      similar peptides.

PMID- 25066912
TI  - Morphometric study of phylogenetic and ecologic signals in procyonid (mammalia:
      carnivora) endocasts.
AB  - Endocasts provide a proxy for brain morphology but are rarely incorporated in
      phylogenetic analyses despite the potential for new suites of characters. The
      phylogeny of Procyonidae, a carnivoran family with relatively limited taxonomic
      diversity, is not well resolved because morphological and molecular data yield
      conflicting topologies. The presence of phylogenetic and ecologic signals in the
      endocasts of procyonids will be determined using three-dimensional geometric
      morphometrics. Endocasts of seven ingroup species and four outgroup species were
      digitally rendered and 21 landmarks were collected from the endocast surface. Two
      phylogenetic hypotheses of Procyonidae will be examined using methods testing for
      phylogenetic signal in morphometric data. In analyses of all taxa, there is
      significant phylogenetic signal in brain shape for both the morphological and
      molecular topologies. However, the analyses of ingroup taxa recover a significant
      phylogenetic signal for the morphological topology only. These results indicate
      support for the molecular outgroup topology, but not the ingroup topology given
      the brain shape data. Further examination of brain shape using principal
      components analysis and wireframe comparisons suggests procyonids possess more
      developed areas of the brain associated with motor control, spatial perception,
      and balance relative to the basal musteloid condition. Within Procyonidae,
      similar patterns of variation are present, and may be associated with increased
      arboreality in certain taxa. Thus, brain shape derived from endocasts may be used
      to test for phylogenetic signal and preliminary analyses suggest an association
      with behavior and ecology.

PMID- 25066913
TI  - Acute UVB-induced epidermal changes assessed by multiphoton laser tomography.
AB  - BACKGROUND: In vivo multiphoton tomography (MPT) of human skin has become a
      valuable tool for non-invasive examination of morphological and biophysical skin
      properties and their alterations. So far, skin changes after UVB irradiation were
      mainly evaluated clinically and histologically. The present study aimed at non
      invasive imaging of histological changes during acute UVB irradiation by
      multiphoton laser tomography. METHODS: In 10 volunteers, five areas were
      irradiated once with an erythematous UVB dose. Multiphoton measurements were
      performed four times, i.e. before irradiation (baseline), and 24, 48 and 72 h
      after irradiation, respectively. The data were evaluated for changes of epidermal
      pleomorphy, spongiosis, pigmentation and thickness. RESULTS: The four parameters
      were altered significantly by acute UVB irradiation, i.e. epidermal pleomorphy,
      spongiosis, pigmentation and thickness increased within 72 h after irradiation.
      CONCLUSION: Thus, the study has shown that typical epidermal changes induced by
      acute UVB irradiation can be evaluated by MPT.

PMID- 25066914
TI  - Fluorinated boron nitride nanotube quantum dots: a spin filter.
AB  - Spin filtering requires a selective transmission of spin-polarized carriers. A
      perfect spin filter allows all majority (or minority) spin carriers to pass
      through a channel while blocking the minority (or majority) carriers. The quest
      for a novel low-dimensional metal-free magnetic material that would exhibit
      magnetism at a higher temperature with an excellent spin filtering property has
      been intensively pursued. Herein, using a first-principles approach, we
      demonstrate that the fluorinated boron nitride nanotube (F-BNNT) quantum dot,
      which is ferromagnetic in nature, can be used as a perfect spin filter with
      efficiency as high as 99.8%. Our calculation shows that the ferromagnetic spin
      ordering in F-BNNT is stable at a higher temperature. Comparison of the
      conductance value of the F-BNNT quantum dot with that of the pristine BNNT
      quantum dot reveals a significantly higher conductance in F-BNNT, which is in
      very good agreement with the experimental report (Tang, C., et al. J. Am. Chem.
      Soc. 2005, 127, 6552).

PMID- 25066915
TI  - Atomic structure of recombinant thaumatin II reveals flexible conformations in
      two residues critical for sweetness and three consecutive glycine residues.
AB  - Thaumatin, an intensely sweet-tasting protein used as a sweetener, elicits a
      sweet taste at 50 nM. Although two major variants designated thaumatin I and
      thaumatin II exist in plants, there have been few dedicated thaumatin II
      structural studies and, to date, data beyond atomic resolution had not been
      obtained. To identify the detailed structural properties explaining why thaumatin
      elicits a sweet taste, the structure of recombinant thaumatin II was determined
      at the resolution of 0.99 A. Atomic resolution structural analysis with riding
      hydrogen atoms illustrated the differences in the direction of the side-chains
      more precisely and the electron density maps of the C-terminal regions were
      markedly improved. Though it had been suggested that the three consecutive
      glycine residues (G142-G143-G144) have highly flexible conformations, G143, the
      central glycine residue was successfully modelled in two conformations for the
      first time. Furthermore, the side chain r.m.s.d. values for two residues (R67 and
      R82) critical for sweetness exhibited substantially higher values, suggesting
      that these residues are highly disordered. These results demonstrated that the
      flexible conformations in two critical residues favoring their interaction with
      sweet taste receptors are prominent features of the intensely sweet taste of
      thaumatin.

PMID- 25066916
TI  - Sex in the night: fatty acid-derived sex pheromones and corresponding membrane
      pheromone receptors in insects.
AB  - The moth sex pheromone communication is one of the most striking examples of
      chemical communication in the animal kingdom. Investigating the molecular
      mechanisms of pheromone biosynthesis in the female pheromone gland and of
      pheromone reception in the male antennae not only defines new concepts in
      signalling research but also opens new perspectives for insect control. In this
      mini-review, we use the cotton leafworm Spodoptera littoralis as a guideline to
      illustrate the recent advances gained in the understanding of moth sex pheromone
      communication. 

PMID- 25066917
TI  - Identification of multiple peptides with antioxidant and antimicrobial activities
      from skin and its secretions of Hylarana taipehensis, Amolops lifanensis, and
      Amolops granulosus.
AB  - Amphibian skin and its secretions contain many kinds of peptides with different
      bioactivities. In this study, a large number of peptides including antioxidant
      and antimicrobial peptides were identified from three East Asian frog species
      Hylarana taipehensis, Amolops lifanensis, and Amolops granulosus. The majority of
      these peptides were antimicrobial peptides, while eight antioxidant peptides were
      identified, which included two novel peptides taipehensin-1TP1
      (TLIWEFYHQILDEYNKENKG) and taipehensin-2TP1 (CLMARPNYRCKIFKQC). These antioxidant
      peptides exhibited the ability to scavenge ABTS and/or DPPH free radicals.
      Moreover, six out of eight antioxidant peptides temporin-TP1, brevinin-1TP1,
      brevinin-1TP2, brevinin-1TP3, brevinin-1LF1, and palustrin-2GN1 also showed
      antimicrobial activity. 

PMID- 25066918
TI  - MAPK11 in breast cancer cells enhances osteoclastogenesis and bone resorption.
AB  - Breast cancer cells frequently metastasize to bone and induce osteolytic bone
      destruction in patients. These metastases cause severe bone pain, high risk of
      fractures and hypercalcemia, and are essentially incurable and fatal. Recent
      studies show that breast cancer cells in bone activate osteoclastogenesis and
      bone resorption. However the underlying mechanism is poorly understood. This
      study shows that the p38 MAPK (p38) isoform MAPK11 (p38beta) is expressed in
      breast cancer cells. By using specific small hairpin RNAs for MAPK11, we
      demonstrated that p38beta-mediated p38 activity in breast cancer cells is
      responsible for breast cancer-induced osteolytic bone destruction. The addition
      of conditioned media from breast cancer cell lines MDA-MB-231 and MDA-MB-468,
      which have high expression of p38beta, induced osteoclast differentiation and
      bone resorption. In contrast, knockdown of p38beta in breast cancer cells reduced
      osteoclast differentiation in vitro and reduced bone destruction in severe
      combined immunodeficiency (SCID) mouse models. The knockdown of p38beta did not
      affect tumor growth or survival or the ability of cancer cells to home to bone.
      Furthermore, our results showed that p38beta upregulated the expression and
      secretion of monocyte chemotactic protein-1 (MCP-1) in breast cancer cells, and
      upregulated MCP-1 activates osteoclast differentiation and activity. This study
      elucidates a novel molecular mechanism of breast cancer cell-induced osteolytic
      bone destruction. This study also indicates that targeting breast cancer cell
      p38beta and its product MCP-1 may be a viable approach to treat or prevent bone
      destruction in patients with bone-metastatic breast cancer.

PMID- 25066919
TI  - Clinical features and types of articular involvement in patients with psoriatic
      arthritis.
AB  - Psoriatic arthritis (PsA) is a psoriasis-associated inflammatory arthritis which
      causes joint destruction. There are some epidemiologic data about PsA; however,
      there are no sufficient data from Turkey. Herein, we evaluated the frequency of
      PsA in the Thrace region of Turkey according to hospital-based data. In addition,
      we evaluated clinical features and types of joint involvement in PsA patients. We
      included 172 PsA patients fulfilling CASPAR criteria admitted to the Division of
      Rheumatology, Trakya University Medical Faculty, between 2003 and 2012. Data from
      Turkish Statistical Institution was used to calculate the incidence and
      prevalence of PsA. Patients' demographic features, durations of psoriasis and
      PsA, number of tender and swollen joints, treatment modalities, laboratory data,
      and X-ray film findings were recorded from hospital files. The annual incidence
      of PsA was 2.8/100,000. The mean annual incidence was 3.47/100,000 in females and
      2.15/100,000 in males. The overall prevalence of PsA in our region was
      27.9/100,000 (95 % confidence interval (CI) 23.7-32.1) in individuals >16 years.
      The prevalence of PsA was higher in females than in males (34.7/100,000 vs.
      21.5/100,000). Polyarthritis was present in 67 (38.9 %), oligoarthritis in 47
      (27.3 %), spondyloarthritis in 39 (22.6 %), and distal interphalangeal (DIP)
      arthritis in 19 (11.0 %) patients. The duration of psoriasis was significantly
      longer in polyarticular PsA patients than in DIP and oligoarticular groups (p
      values = 0.016 and 0.018, respectively). The number of swollen joints correlated
      with age (r = 0.21, p = 0.006), duration of psoriasis (r = 0.20, p = 0.01),
      number of tender joints (r = 0.92, p <= 0.001), ESR (r = 0.24, p = 0.001), and
      CRP (r = 0.17, p = 0.026). The frequency of PsA in Thrace region is similar to
      that in low-frequency regions. The most frequent type of involvement was
      polyarticular, and it correlated with the duration of psoriasis and erosive
      disease.

PMID- 25066920
TI  - Long term safety of sacral nerve modulation in medicare beneficiaries.
AB  - AIMS: Sacral nerve stimulation (SNS) is FDA approved as second-line therapy for
      both urinary and bowel control. However, there is limited evidence regarding long
      term safety. We determined adverse events associated with SNS among Medicare
      beneficiaries. METHODS: We used the 5% national random sample of Medicare claims
      for 2001-2011 to identify patients. Patients who underwent SNS implantation were
      identified with Current Procedure Terminology (CPT-4) codes. We determined safety
      of SNS using analysis of complication occurrences on day of surgery and during 5
      years following initial procedure. SAS v9.3 statistical package was used.
      RESULTS: One thousand four hundred seventy-four patients underwent treatment with
      SNS in the 5% national sample of Medicare patients within the time period.
      Representative of real-world patients undergoing SNS surgery, comorbidities
      included hypertension (69.3%), diabetes (29.4%), chronic pulmonary disease
      (25.5%), hypothyroidism (25.2%), and depression (22.7%). Few complications
      occurred on day of surgery. At 90 days, 3.2% of patients had bowel complications,
      2.0% urological, 9.4% infectious, and 1.5% stroke. Overall, bowel, neurological
      health event occurrences were consistent with prior year rates, while infectious
      events decreased. Of 206 patients who were followed for at least 5 years, 17.3%
      had devices removed and 11.3% replaced, with 26.1% having at least one of those,
      leaving 73.9% with original devices. CONCLUSIONS: Urological, infectious, and
      bowel complication occurrences were low after SNS among Medicare beneficiaries
      with multiple comorbidities. There were infrequent serious complications like
      hemorrhage and stroke postoperatively. Although SNS appears safe in this high
      risk population, a comprehensive registry will ensure continuous safety.

PMID- 25066921
TI  - Design and rationale of a comparative effectiveness trial evaluating
      transcendental meditation against established therapies for PTSD.
AB  - BACKGROUND: Although meditation therapies such as the Transcendental Meditation
      (TM) technique are commonly used to assist with stress and stress-related
      diseases, there remains a lack of rigorous clinical trial research establishing
      the relative efficacy of these treatments overall and for populations with
      psychiatric illness. This study uses a comparative effectiveness design to assess
      the relative benefits of TM to those obtained from a gold-standard cognitive
      behavioral therapy for posttraumatic stress disorder (PTSD) in a Veteran
      population. METHODS AND DESIGN: This paper describes the rationale and design of
      an in progress randomized controlled trial comparing TM to an established
      cognitive behavioral treatment - Prolonged Exposure (PE) - and an active control
      condition (health education [HE]) for PTSD. This trial will recruit 210 Veterans
      meeting DSM-IV criteria for PTSD, with testing conducted at 0 and 3 months for
      PTSD symptoms, depression, mood disturbance, quality of life, behavioral factors,
      and physiological/biochemical and gene expression mechanisms using validated
      measures. The study hypothesis is that TM will be noninferior to PE and superior
      to HE on changes in PTSD symptoms, using the Clinician Administered PTSD Scale
      (CAPS). DISCUSSION: The described study represents a methodologically rigorous
      protocol evaluating the benefits of TM for PTSD. The projected results will help
      to establish the overall efficacy of TM for PTSD among Veterans, identify bio
      behavioral mechanisms through which TM and PE may improve PTSD symptoms, and will
      permit conclusions regarding the relative value of TM against currently
      established therapies for PTSD.

PMID- 25066922
TI  - T-cell immunoglobulin and mucin domain 4 (TIM-4) signaling in innate immune
      mediated liver ischemia-reperfusion injury.
AB  - Hepatic ischemia-reperfusion injury (IRI), an innate immunity-driven inflammation
      response, occurs in multiple clinical settings including liver resection,
      transplantation, trauma, and shock. T-cell immunoglobulin and mucin (TIM)-4, the
      only TIM protein not expressed on T cells, is found on macrophages and dendritic
      cells. The regulatory function of macrophage TIM-4 in the engulfment of
      apoptotic/necrotic bodies in innate immunity-mediated disease states remains
      unknown. This study focuses on the putative role of TIM-4 signaling in a model of
      liver warm ischemia (90 minutes) and reperfusion. The ischemia insult triggered
      TIM-4 expression by stressed hepatocellular phosphatidylserine (PS) presentation,
      peaking at 6 hours of reperfusion, and coinciding with the maximal hepatocellular
      damage. TIM-4-deficient or wild-type WT mice treated with antagonistic TIM-4
      monoclonal antibody (mAb) were resistant against liver IRI, evidenced by
      diminished serum alanine aminotransferase (sALT) levels and well-preserved
      hepatic architecture. Liver hepatoprotection rendered by TIM-4 deficiency was
      accompanied by diminished macrophage infiltration/chemoattraction, phagocytosis,
      and activation of Toll-like receptor (TLR)2/4/9-dependent signaling. Correlating
      with in vivo kinetics, the peak of TIM-4 induction in lipopolysaccharide (LPS)
      activated bone marrow derived-macrophages (BMM) was detected in 6-hour cultures.
      To mimic liver IRI, we employed hydrogen peroxide-necrotic hepatocytes, which
      readily present PS. Indeed, necrotic hepatocytes were efficiently
      captured/engulfed by WT (TIM-4+) but not by TIM-4-deficient BMM. Finally, in a
      newly established model of liver IRI, adoptive transfer of WT but not TIM-4
      deficient BMM readily recreated local inflammation response/hepatocellular damage
      in the CD11b-DTR mouse system. CONCLUSION: These findings document the importance
      of macrophage-specific TIM-4 activation in the mechanism of hepatic IRI.
      Macrophage TIM-4 may represent a therapeutic target to minimize innate
      inflammatory responses in IR-stressed organs.

PMID- 25066923
TI  - Phylogenetic exploration of commonly used medicinal plants in South Africa.
AB  - The rapid growth rate of human population, along with the public health crisis
      encountered in many regions, particularly in developing world, creates an urgent
      need for the discovery of alternative drugs. Because medicinal plants are not
      distributed randomly across lineages, it has been suggested that phylogeny along
      with traditional knowledge of plant uses can guide the identification of new
      medicinally useful plants. In this study, we combined different statistical
      approaches to test for phylogenetic signal in 33 categories of plant uses in
      South Africa. Depending on the null models considered, we found evidence for
      signal in up to 45% of plant use categories, indicating the need for multiple
      tests combination to maximize the chance of discovering new medicinal plants when
      applying a phylogenetic comparative approach. Furthermore, although there was no
      signal in the diversity of medicinal uses-that is, total number of medicinal uses
      recorded for each plant-our results indicate that taxa that are evolutionarily
      closely related have significantly more uses than those that are evolutionarily
      isolated. Our study therefore provides additional support to the body of the
      literature that advocates for the inclusion of phylogeny in bioscreening
      medicinal flora for the discovery of alternative medicines. 

PMID- 25066924
TI  - Mild cold-stress depresses immune responses: Implications for cancer models
      involving laboratory mice.
AB  - Physiologically accurate mouse models of cancer are critical in the pre-clinical
      development of novel cancer therapies. However, current standardized animal
      housing temperatures elicit chronic cold-associated stress in mice, which is
      further increased in the presence of tumor. This cold-stress significantly
      impacts experimental outcomes. Data from our lab and others suggest standard
      housing fundamentally alters murine physiology, and this can produce altered
      immune baselines in tumor and other disease models. Researchers may thus
      underestimate the efficacy of therapies that are benefitted by immune responses.
      A potential mediator, norepinephrine, also underlies stress pathways common in
      mice and humans. Therefore, research into mechanisms connecting cold-stress and
      norepinephrine signaling with immune depression in mice could highlight new
      combination therapies for humans to simultaneously target stress while
      stimulating anti-tumor immunity. 

PMID- 25066925
TI  - Molecular cloning and characterization of secretory and membrane-bound IgM of
      turbot.
AB  - In recent years, increasing diseases especially bacterial diseases have brought a
      host of losses with the expansive cultivation of turbot (Scophthalmus maximus).
      In order to do more research about the immune system of turbot for better
      understanding the mechanism of resisting diseases, the immunoglobulin genes
      related to secretory and membrane-bound IgM (s-IgM and m-IgM) of turbot were
      cloned using homology sequences cloning and SMART RACE PCR method. The heavy
      chain of s-IgM cDNA is 1900 bp in length including a leader region, a variable
      region, four constant regions (CH1, CH2, CH3 and CH4) and a C-terminal while the
      cDNA of m-IgM is 1795 bp with the same leader region, variable region, three
      constant regions (CH1, CH2 and CH3) and two transmembrane regions (TM1 and TM2).
      The sequence of IgM gene was also obtained and the structure consisted of V-CH1
      CH2-CH3-CH4-TM1-TM2 is similar to other fishes. The highest level of s-IgM
      expression was observed in spleen, followed by kidney, gills, eyes, skin of the
      healthy turbot whereas the same profile of m-IgM expression is found with low
      level. And s-IgM takes up dominant proportion of total IgM expression. Also the
      relative expressions of s-IgM and m-IgM were analyzed in turbot vaccinated with
      the live attenuated vaccine Vibrio anguillarum. Not only the transcriptions of
      both s-IgM and m-IgM in liver, spleen and kidney of turbot injected with V.
      anguillarum MVAV6203 were up-regulated but also the expressions of s-IgM and m
      IgM in spleen, kidney, gut, skin and gills of bath-vaccinated turbot were
      increased. Comparing the ratio changes of relative expression of m-IgM and s-IgM
      in vaccinated turbot, we found that the proportion of m-IgM were increasing in
      both administration routes, which probably indicated that the increasing
      expression of m-IgM strengthen the phagocytic ability of B cells.

PMID- 25066926
TI  - A new rhodamine-based fluorescent chemodosimeter for mercuric ions in water
      media.
AB  - A new rhodamine-ethylenediamine-nitrothiourea conjugate (RT) was synthesized and
      its sensing property as a fluorescent chemodosimeter toward metal ions was
      explored in water media. Analytical results from absorption and fluorescence
      spectra revealed that the addition of Hg(2+) ions to the aqueous solution of the
      chemodosimeter RT caused a distinct fluorescence OFF-ON response with a
      remarkable visual color change from colorless to pink; however, no clear spectral
      and color changes were observed from other metal ions including: Zn(2+) , Cu(2+)
      , Cd(2+) , Pb(2+) , Ag(+) , Fe(2+) , Cr(3+) , Co(3+) , Ni(2+) , Ca(2+) , Mg(2+) ,
      K(+) and Na(+) . The sensing results and the molecular structure suggested that a
      Hg(2+) -induced a desulfurization reaction and cyclic guanylation of the thiourea
      moiety followed by ring-opening of the rhodamine spirolactam in RT are
      responsible for a distinct fluorescence turn-on signal, indicating that RT is a
      remarkably sensitive and selective chemodosimeter for Hg(2+) ions in aqueous
      solution. Hg(2+) within a concentration range from 0.1 to 25 MUM can be
      determined using RT as a chemodosimeter and a detection limit of 0.04 MUM is
      achieved.

PMID- 25066927
TI  - Feasibility and acceptability of an iPad application to explore symptom clusters
      in adolescents and young adults with cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility and
      acceptability of a computer-based symptom cluster heuristics tool designed to
      explore symptom clusters experienced by adolescents and young adults (AYAs) with
      cancer. The Computerized Symptom Capture Tool (C-SCAT) is a newly developed iPad
      application, which combines graphical images and free text responses in an
      innovative heuristics approach to explore symptoms and symptom clusters.
      PROCEDURE: Seventy-two AYAs (13-29 years of age) with cancer at five institutions
      across the US completed the C-SCAT 24-96 hours after the initial chemotherapy
      dose in a chemotherapy cycle. RESULTS: All participants completed the C-SCAT
      successfully in a mean of 25 minutes, with 74% reporting that the final image was
      an accurate or very accurate representation of their symptom experience. Little
      clarification/coaching was necessary while completing the C-SCAT. Few technical
      problems were encountered. Participants judged the C-SCAT questions to be clear
      and endorsed ease of following instructions, typing, and drawing. CONCLUSIONS:
      The C-SCAT demonstrated feasibility and acceptability. With refinement based on
      study results, the C-SCAT has potential to: (a) empower AYAs to communicate their
      symptom experience and partner with providers in their care; (b) improve symptom
      management and ameliorate distress; and (c) translate to use with other highly
      symptomatic populations.

PMID- 25066928
TI  - Imaging evidence for endothelin ETA/ETB receptor heterodimers in isolated rat
      mesenteric resistance arteries.
AB  - AIMS: In engineered cells, endothelin ETA and ETB receptors can heterodimerize.
      We tested whether this can also be observed in native tissue. MAIN METHODS: Rat
      mesenteric resistance arteries (rMRA) were maintained in organ culture for 24h to
      upregulate ETB-mediated contractions in addition to their normal ETA-mediated
      responses. They were then exposed to 100 nM linear ET-1 (ETB-agonist) labeled
      with Oregon Green 488 (OG488/L.-ET-1) and/or to 16nM intact ET-1 (ETA/ETB
      agonist) labeled with the rhodamine dye TAMRA (TAMRA/ET-1). Two photon laser
      scanning microscopy (TPLSM) was used for the visualization of their binding in
      the tissue. Fluorescence Lifetime Imaging Microscopy (FLIM) was employed for
      measurements of the OG488/L.-ET-1 lifetime in the absence and presence of
      TAMRA/ET-1. KEY FINDINGS: After incubation with the labeled ligands, medial
      smooth muscle cells (SMCs) were efficiently stained and became visible under
      TPLSM. TAMRA/ET-1 bound to all SMCs whereas OG488/L.-ET-1 stained only groups of
      SMCs. Interaction of the two receptor subtypes in SMC was investigated in double
      staining experiments. Fluorescence lifetime of OG488/L.-ET-1 was reduced in the
      presence of TAMRA/ET-1, which indicates the occurrence of Fluorescence Resonant
      Energy Transfer (FRET) and suggests close proximity of the two receptor subtypes
      within the arterial wall. SIGNIFICANCE: The methodology that is introduced by
      these new observations may be useful to assess ET-receptor heterodimerization in
      biopsies from relevant experimental animal models and human patients.

PMID- 25066929
TI  - Glucose dominates the regulation of carboxylesterases induced by
      lipopolysaccharide or interleukin-6 in primary mouse hepatocytes.
AB  - AIMS: Altered drug disposition has been associated with inflammation and
      diabetes, leading to the alteration of drug efficacy and toxicity.
      Carboxylesterases are major hydrolytic enzymes in the liver, catalyzing the
      hydrolytic biotransformation of numerous therapeutic agents. Therefore, how
      glucose affects the regulation of carboxylesterases by interleukin-6 (IL-6) and
      lipopolysaccharide (LPS) were investigated. MAIN METHODS: Primary mouse
      hepatocytes were cultured. Protein levels were measured by Western blot or enzyme
      linked immunosorbent assay (ELISA), while confocal laser scanning microscope and
      flow cytometry were used to confirm the activation of pregnane X receptor (PXR).
      Carboxylesterase activity was evaluated by enzymatic and toxicological assays.
      KEY FINDINGS: Elevated glucose (11 or 25 mM) significantly increased
      carboxylesterase expression compared to 5.6 mM glucose. Carboxylesterase
      expression and activity were inhibited by LPS or IL-6 in 25 mM glucose, but
      stimulated in 5.6 mM glucose. The altered expression of carboxylesterases was not
      consistent with the activation of nuclear factor kappa B (NFkappaB) but
      repeatedly with the expression and activation of pregnane X receptor (PXR). The
      altered activation of PXR was further evidenced by the differential subcellular
      translocation and the expression of its target gene multidrug resistance 1
      (MDR1). It implies that PXR, instead of inflammatory signaling, mediates the
      regulation of carboxylesterases by inflammatory mediators in different glucose
      concentrations. SIGNIFICANCE: The findings contribute to clarify the regulation
      of carboxylesterases by inflammatory mediators, and indicate that
      carboxylesterase-involved drug metabolism and drug-drug interactions in diabetes
      should be reevaluated according to the intensity of inflammatory reactions and
      hyperglycemia.

PMID- 25066930
TI  - Up-regulation of cyclinD1 and Bcl2A1 by insulin is involved in osteoclast
      proliferation.
AB  - AIMS: Insulin receptor signaling in osteoblasts has been well established, but
      the effects of insulin on osteoclast proliferation are poorly explored. The
      objective of this study was to investigate the roles and the mechanisms of
      insulin on osteoclast proliferation. MAIN METHODS: After insulin treatment to
      primary osteoclast precursors, BrdU incorporation assay was performed and the
      expression of cell cycle- and apoptosis-related genes was determined by real-time
      PCR and immunoblotting. Apoptosis was analyzed using a FACScan flow cytometer.
      KEY FINDINGS: Insulin activated insulin receptor and promoted the proliferation
      of osteoclast precursors in time- and dose-dependent manners. However, the
      expression of insulin receptor was not changed by it during that time. Insulin
      remarkably induced the expression of cyclinD1, a cell cycle marker, and Bcl2A1,
      an anti-apoptotic oncogene, whereas cdk1 and cdk4 were not affected by it. The
      expression of Bcl2l11 and Bax, both apoptotic markers, was reduced or not changed
      in osteoclast precursors. Bcl2A1/Bax ratio was also increased in protein levels.
      Treatment with obatoclax, a Bcl2 family inhibitor, significantly induced the
      apoptosis of osteoclast precursors in the presence of insulin. These results
      demonstrate that insulin promotes osteoclast proliferation by increasing cell
      cycle and suppressing apoptosis through specific gene regulation. SIGNIFICANCE:
      These data provide a basis for understanding and ultimately treating several bone
      related metabolic diseases.

PMID- 25066931
TI  - Paleomobility in the Tiwanaku diaspora: biogeochemical analyses at Rio Muerto,
      Moquegua, Peru.
AB  - Paleomobility has been a key element in the study of the expansion of ancient
      states and empires, including the Tiwanaku polity of the South Central Andes (AD
      500-1000). We present radiogenic strontium and oxygen isotope data from human
      burials from three cemeteries in the Tiwanaku-affiliated Middle Horizon
      archaeological site complex of Rio Muerto in the Moquegua Valley of southern
      Peru. At Rio Muerto, archaeological human enamel and bone values range from (87)
      Sr/(86) Sr = 0.70657-0.72018, with a mean of (87) Sr/(86) Sr = 0.70804 +/-
      0.00207 (1sigma, n = 55). For the subset of samples analyzed for oxygen isotope
      values (n = 48), the data ranges from delta(18) Ocarbonate(VSMOW)  = +18.1 to
      +27.00/00. When contextualized with other lines of archaeological evidence, we
      interpret these data as evidence for an archaeological population in which the
      majority of individuals had "local" origins, and were likely second-generation,
      or more, immigrants from the Tiwanaku heartland in the altiplano. Based on
      detailed life history data, we argue a smaller number of individuals came at
      different ages from various regions within the Tiwanaku polity. We consider
      whether these individuals with isotopic values consistent with "nonlocal"
      geographic origins could represent first-generation migrants, marriage exchange
      partners, or occupationally mobile herders, traders or other travelers. By
      combining isotopic life history studies with mortuary treatment data, we use a
      person-centered migration history approach to state integration and expansion.
      Isotopic analyses of paleomobility at the Rio Muerto site complex contribute to
      the role of diversity in ancient states by demonstrating the range of geographic
      origins rather than simply colonists from the Lake Titicaca Basin.

PMID- 25066932
TI  - The in vitro digestibility of beef varies with its inherent ultimate pH.
AB  - Animal carcasses and cuts of meat are usually differentiated and valued according
      to size and compositional attributes. An underappreciated variable of red meat is
      its inherent ultimate pH (pHu) value, which affects organoleptic and processing
      characteristics. This study tests the hypothesis that high pHu aged meat would be
      more digestible than low pHu unaged (fresh) meat. Longissimus dorsi muscles
      collected from 59 bull carcasses had pHu values of 5.6-6.9. These were aged for
      21 days at -1.5  degrees C, then raw and cooked (72  degrees C) samples were
      enzymatically digested at 37  degrees C with pepsin (pH 1.9 for 90 min) followed
      by pancreatin (pH 8.0 for an additional 120 min) to simulate conditions in the
      stomach and small intestine, respectively. Meat proteins and peptides in the
      digests were separated by 1D SDS PAGE. Regardless of pHu, ageing or cooking, most
      sarcoplasmic and myofibrillar proteins were rapidly digested by pepsin, with
      concomitant release of products identified by LC-MS/MS as mainly myosin-1, -2 and
      -7, alpha-actinin-2 or -3 and tropomyosin beta and alpha chains. These products
      were resistant to further digestion for the entire 210 min duration of the
      incubation. In terms of rate and extent of digestibility of these resistant
      products, high pHu > low pHu (P < 0.001), whereas aged > unaged (P < 0.003), with
      the effect of cooking dependent on pHu and varying somewhat by protein. Overall,
      the digestibility of meat samples increased with increasing pHu (P < 0.001). Beef
      meat was highly digestible but could be further differentiated on the basis of
      its pHu and the ease of digestibility of proteins. Specific carcasses or cuts
      could be targeted to consumer groups in order to provide benefits and add value. 

PMID- 25066933
TI  - Early development, stress and depression across the life course: pathways to
      depression in a national British birth cohort.
AB  - BACKGROUND: The aetiology of depression is multifactorial, with biological,
      cognitive and environmental factors across the life course influencing risk of a
      depressive episode. There is inconsistent evidence linking early life development
      and later depression. The aim of this study was to investigate relationships
      between low birthweight (LBW), infant neurodevelopment, and acute and chronic
      stress as components in pathways to depression in adulthood. METHOD: The sample
      included 4627 members of the National Survey of Health and Development (NSHD; the
      1946 British birth cohort). Weight at birth, age of developmental milestones,
      economic deprivation in early childhood, acute stressors in childhood and
      adulthood, and socio-economic status (SES) in adulthood were assessed for their
      direct and indirect effects on adolescent (ages 13 and 15 years) and adult (ages
      36, 43 and 53 years) measures of depressive symptoms in a structural equation
      modelling (SEM) framework. A structural equation model developed to incorporate
      all variables exhibited excellent model fit according to several indices.
      RESULTS: The path of prediction from birthweight to age of developmental
      milestones to adolescent depression/anxiety to adult depression/anxiety was
      significant (p < 0.001). Notably, direct paths from birthweight (p = 0.25) and
      age of developmental milestones (p = 0.23) to adult depression were not
      significant. Childhood deprivation and stressors had important direct and
      indirect effects on depression. Stressors in adulthood were strongly associated
      with adult depression. CONCLUSIONS: Depression in adulthood is influenced by an
      accumulation of stressors across the life course, including many that originate
      in the first years of life. Effects of early-life development on mental health
      appear by adolescence.

PMID- 25066934
TI  - Usual interstitial pneumonia and smoking-related interstitial fibrosis display
      epithelial to mesenchymal transition in fibroblastic foci.
AB  - BACKGROUND: Fibroblastic foci (FF) are a major histological feature of usual
      interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen
      vascular diseases (non-IPF). In addition, FF are occasionally associated with
      smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a
      role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis.
      METHODS: Here, we investigated whether EMT was present in patients with IPF (n =
      19), non-IPF (n = 17), and SRIF (n = 16) using morphometric immunohistochemistry,
      electron microscopy, and confocal microscopy. All patients had received lung
      biopsies or lobectomies for lung cancer. RESULTS: IPF and non-IPF patients
      displayed restrictive lung function patterns, whereas those with SRIF presented
      mixed patterns. Cells within FF presented high number of alpha-smooth muscle
      actin (alphaSMA)-staining cells; however, the foci of IPF patients showed
      comparatively lower number. Moreover, colocalization of thyroid transcription
      factor-1 (TTF1) and alphaSMA within FF showed low number of staining cells for
      IPF and SRIF in comparison to non-IPF (p < 0.01). Nevertheless, all groups
      displayed colocalization of high rate of TTF1(+)-cells and low rate of
      alphaSMA(+)-cells within hyperplastic epithelioid cells in FF. Also, we observed
      areas with low proportion of TTF1(+)cells and alphaSMA(+)cells, which were
      present in SRIF and non-IPF more often than IPF (p < 0.001). Electron microscopy
      revealed small breaks in the alveolar basal lamina, which allowed epithelioid
      cells to directly contact the collagenous matrix and fibroblasts. Three
      dimensional reconstruction revealed intense alphaSMA staining within some
      epithelioid cells, suggesting that they had gained a mesenchymal phenotype.
      CONCLUSIONS: These findings constitute the first report of EMT in SRIF and
      suggest that EMT occurs more prominently in SRIF and non-IPF than IPF.

PMID- 25066935
TI  - Exercise and physical training improve physical function in older adults with
      visual impairments but their effect on falls is unclear: a systematic review.
AB  - QUESTION: Can exercise or physical training improve physical function and prevent
      falls in older adults with visual impairments? DESIGN: Systematic review of
      randomised controlled trials with meta-analysis. PARTICIPANTS: Older adults (>=
      60 years) with visual impairments. INTERVENTION: Individual or group exercise or
      physical training classes in any settings. OUTCOME MEASURES: Mobility, balance,
      strength and proprioception measured with performance tests or questionnaires
      and/or falls with calendars or incident reports. RESULTS: Four eligible trials
      with a total of 522 participants were identified. Multimodal group exercise (n =
      50 and 41) and Tai Chi (n=40) improved physical function among residents of care
      settings. Meta-analysis of data from two trials indicated a significant positive
      impact of multimodal exercise on the Berg Balance Score (weighted mean difference
      3.9 points, 95% CI 1.8 to 6.0), but not on the Timed Up and Go test (weighted
      mean difference 1.5seconds, 95% CI -1.7 to 4.6). One trial (n=41) found that
      multimodal exercise reduced the time to first fall (p=0.049). A factorial trial
      (n=391) among community dwellers did not find a significant effect on falls from
      a home-based exercise intervention, although clinically relevant effects in
      either direction were not excluded by the study (incidence rate ratio=1.15, 95%
      CI 0.82 to 1.61). CONCLUSION: Exercise interventions in residential care settings
      improve performance on some tests of physical function that are risk factors for
      falls but the impact on falls is not yet clear. The impact of exercise and
      training on physical function and falls in community-dwelling older adults with
      visual impairments also warrants further investigation.

PMID- 25066936
TI  - Five-repetition sit-to-stand.

PMID- 25066937
TI  - Determination of resin acid composition in rosin samples using cyclodextrin
      modified capillary electrophoresis.
AB  - Rosins are used in a wide variety of industries in varnishes, adhesives, drug
      coatings, etc. In this project a novel capillary electrophoresis method was
      developed to investigate the resin acid composition of rosins. The acids were
      separated and the concentrations of individual acids present in gum rosin samples
      determined in order to investigate any links between the presence and
      concentration of these acids and the tendency of rosins to crystallize. The
      capillary electrophoresis method successfully separated nine resin acids in
      various rosin samples where previously they could not all be separated.
      Calibration curves were created to determine acid concentration. Abietic,
      dehydroabietic, neoabietic, pimaric, isopimaric, levopimaric, sandaracopimaric,
      palustric, and 7-oxo-dehydroabietic acids were separated using a 20 mM tris
      buffer at pH 9 containing 15% methanol 5 mM (2-hydroxypropyl)-gamma-cyclodextrin
      10 mM sulfobutylether-beta-cyclodextrin. Their concentrations in a crystallizing
      and a noncrystallizing rosin sample were determined.

PMID- 25066938
TI  - Subcortical encoding of speech cues in children with attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: There is little information about processing of nonspeech and speech
      stimuli at the subcortical level in individuals with attention deficit
      hyperactivity disorder (ADHD). The auditory brainstem response (ABR) provides
      information about the function of the auditory brainstem pathways. We aim to
      investigate the subcortical function in neural encoding of click and speech
      stimuli in children with ADHD. METHODS: The subjects include 50 children with
      ADHD and 34 typically developing (TD) children between the ages of 8 and 12
      years. Click ABR (cABR) and speech ABR (sABR) with 40 ms synthetic /da/ syllable
      stimulus were recorded. RESULTS: Latencies of cABR in waves of III and V and
      duration of V-Vn (P?0.027), and latencies of sABR in waves A, D, E, F and O and
      duration of V-A (P?0.034) were significantly longer in children with ADHD than in
      TD children. There were no apparent differences in components the sustained
      frequency following response (FFR). CONCLUSIONS: We conclude that children with
      ADHD have deficits in temporal neural encoding of both nonspeech and speech
      stimuli. SIGNIFICANCE: There is a common dysfunction in the processing of click
      and speech stimuli at the brainstem level in children with suspected ADHD.

PMID- 25066939
TI  - Neurophysiological basis of creativity in healthy elderly people: a multiscale
      entropy approach.
AB  - OBJECTIVES: Creativity, which presumably involves various connections within and
      across different neural networks, reportedly underpins the mental well-being of
      older adults. Multiscale entropy (MSE) can characterize the complexity inherent
      in EEG dynamics with multiple temporal scales. It can therefore provide useful
      insight into neural networks. Given that background, we sought to clarify the
      neurophysiological bases of creativity in healthy elderly subjects by assessing
      EEG complexity with MSE, with emphasis on assessment of neural networks. METHODS:
      We recorded resting state EEG of 20 healthy elderly subjects. MSE was calculated
      for each subject for continuous 20-s epochs. Their relevance to individual
      creativity was examined concurrently with intellectual function. RESULTS: Higher
      individual creativity was linked closely to increased EEG complexity across
      higher temporal scales, but no significant relation was found with intellectual
      function (IQ score). CONCLUSIONS: Considering the general "loss of complexity"
      theory of aging, our finding of increased EEG complexity in elderly people with
      heightened creativity supports the idea that creativity is associated with
      activated neural networks. SIGNIFICANCE: Results reported here underscore the
      potential usefulness of MSE analysis for characterizing the neurophysiological
      bases of elderly people with heightened creativity.

PMID- 25066940
TI  - Improved stability and half-life of fluorinated phosphotriesterase using Rosetta.
AB  - Recently we demonstrated that incorporating p-fluorophenylalanine (pFF) into
      phosphotriesterase dramatically improved folding, thereby leading to enhanced
      stability and function at elevated temperatures. To further improve the stability
      of the fluorinated enzyme, Rosetta was used to identify multiple potential
      stabilizing mutations. One such variant, pFF-F104A, exhibited enhanced activity
      at elevated temperature and maintained activity over many days in solution at
      room temperature. 

PMID- 25066941
TI  - Symmetric corticospinal excitability and representation of vastus lateralis
      muscle in right-handed healthy subjects.
AB  - The purpose of this study was to determine the size and location of the
      representations of the anterior thigh muscles on the human motor cortex in the
      dominant and non-dominant hemispheres. Motor-evoked potentials (MEPs) induced by
      transcranial magnetic stimulation were recorded from the right and left vastus
      lateralis (rVL, lVL) muscles. A total of ten right-handed healthy volunteers
      participated in the study. In a single session experiment, we investigated VL
      muscle corticospinal excitability (motor threshold, MEP size, short interval
      intracortical inhibition, intracortical facilitation) and cortical representation
      (map area, volume, and location) in the dominant and non-dominant hemispheres.
      The motor threshold, MEPs, and intracortical excitability did not differ
      significantly between the hemispheres (P > 0.05). Furthermore, no difference
      between sides was found in the location of VL motor representation (mediolateral
      and anteroposterior axis) or in map area and volume (P > 0.05). Vastus lateralis
      muscle corticospinal excitability and cortical map were symmetrical in right
      handed subjects. Future studies on patients with unilateral lower extremity
      injuries could examine side-to-side plastic reorganization in corticomotor output
      and map location in both hemispheres.

PMID- 25066942
TI  - Rusie Dutton traditional Thai exercise promotes health related physical fitness
      and quality of life in menopausal women.
AB  - OBJECTIVE: To examine the effects of "Rusie Dutton" on health and quality of life
      in menopausal women. METHOD: Menopausal women (aged 45-59) were recruited and
      randomly allocated to 2 groups. Rusie Dutton group (n = 24) practiced Rusie
      Dutton conducted by Wat Pho Thai Traditional Massage School for 13 weeks. The
      control group (n = 26) was assigned to a waiting list and received no
      intervention. BW, BMI, restingHR, BP, flexibility, VO2max, and MENQOL including
      vasomotor, physical, psychosocial and sexual domains were measured at the
      beginning and the end. A paired-sample t-test and independent sample t-test were
      used for statistical analysis. RESULTS: Significant improvement was found in all
      variables within group (p < .05) in Rusie Dutton group, and a significant
      difference between groups was found (p < .05) in all variables except BW and BMI.
      Therefore, it is concluded that the traditional Thai exercise Rusie Dutton can
      promote health related physical fitness and QOL in menopausal women.

PMID- 25066943
TI  - Gender differences between hypocretin/orexin knockout and wild type mice: age,
      body weight, body composition, metabolic markers, leptin and insulin resistance.
AB  - Female hypocretin knockout (Hcrt KO) mice have increased body weight despite
      decreased food intake compared to wild type (WT) mice. In order to understand the
      nature of the increased body weight, we carried out a detailed study of Hcrt KO
      and WT, male, and female mice. Female KO mice showed consistently higher body
      weight than WT mice, from 4 to 20 months (20-60%). Fat, muscle, and free fluid
      levels were all significantly higher in adult (7-9 months) as well as old (18-20
      months) female KO mice compared to age-matched WT mice. Old male KO mice showed
      significantly higher fat content (150%) compared to age-matched WT mice, but no
      significant change in body weight. Respiratory quotient (-19%) and metabolic
      rates (-14%) were significantly lower in KO mice compared to WT mice, regardless
      of gender or age. Female KO mice had significantly higher serum leptin levels
      (191%) than WT mice at 18-20 months, but no difference between male mice were
      observed. Conversely, insulin resistance was significantly higher in both male
      (73%) and female (93%) KO mice compared to age- and sex-matched WT mice. We
      conclude that absence of the Hcrt peptide has gender-specific effects. In
      contrast, Hcrt-ataxin mice and human narcoleptics, with loss of the whole Hcrt
      cell, show weight gain in both sexes.

PMID- 25066944
TI  - Anti-inflammatory effect of 635 nm irradiations on in vitro direct/indirect
      irradiation model.
AB  - Low-level laser therapy (LLLT) has been promoted for its beneficial effects on
      tissue healing and pain relief. As during laser treatment it is possible to
      irradiate only a small area of the surface body or wound and, correspondingly, of
      a very small volume of the circulating blood, it is necessary to explain how its
      photomodification can lead to a wide spectrum of therapeutic effects. To
      establish the experimental model for indirect irradiation, irradiation with 635
      nm was performed on immortalized human gingival fibroblasts (IGFs) in the
      presence of Porphyromonas gingivalis lipopolysaccharides (LPS). The irradiated
      medium was transferred to non-irradiated IGFs which were compared with direct
      irradiated IGFs. The protein expressions were assessed by Western blot, and
      prostaglandin E2 (PGE2 ) was measured using an enzyme-linked immunoassay.
      Reactive oxygen species (ROS) were measured by DCF-DA; cytokine profiles were
      assessed using a human inflammation antibody array. Cyclooxygenase-2 (COX-2)
      protein expression and PGE2 production were significantly increased in the LPS
      treated group and decreased in both direct and indirect irradiated IGFs. Unlike
      direct irradiated IGFs, ROS level in indirect irradiated IGFs was decreased by
      time-dependent manners. There were significant differences of released
      granulocyte colony-stimulating factor (G-CSF), regulated on activated normal T
      cell expressed and secreted (RANTES), and I-TAC level observed compared with
      direct and indirect irradiated IGFs. In addition, in the indirect irradiation
      group, phosphorylations of C-Raf and Erk1/2 increased significantly compared with
      the direct irradiation group. Thus, we suggest that not only direct exposure with
      635 nm light, but also indirect exposure with 635 nm light can inhibit activation
      of pro-inflammatory mediators and may be clinically useful as an anti
      inflammatory tool. 

PMID- 25066945
TI  - Response from authors to letter from Eduardo Hernandez-Garduno (TUBE 2013_75)
      Tuberculosis monoresistance and culture conversion in smokers Nijenbandring de
      Boer R, et al., "Delayed culture conversion due to cigarette smoking in active
      pulmonary tuberculosis patients, Tuberculosis (2014) January".

PMID- 25066946
TI  - A One Health, participatory epidemiology assessment of anthrax (Bacillus
      anthracis) management in Western Uganda.
AB  - Sporadic anthrax outbreaks have occurred in and around Uganda's Queen Elizabeth
      National Park (QENP) for years, affecting wildlife, domestic animals, and humans.
      Reported outbreaks (2004-2005 and 2010) in QENP collectively killed over 500 wild
      animals and over 400 domestic animals. A 2011 outbreak in Sheema district
      temporarily froze local markets while killing two humans and seven bovines. One
      Health is multidisciplinary at its core, yet studies sometimes focus on the
      effects of animals on human health to the detriment of investigating the
      surrounding ecological and cultural contexts. Participatory methods connect
      problems - such as disease - to their context. A multidisciplinary team used
      participatory epidemiology and conventional structured questionnaires to
      investigate the impacts of anthrax on human livelihoods and the related
      perceptions of conservation, public health, and veterinary health efforts in the
      QENP area. Proximities to previous anthrax outbreaks and to QENP were treated as
      risk factors in the collection and evaluation of data. Participants' feedback
      indicates that anthrax prevalence may be greater than officially reported.
      Community member perceptions about anthrax and other diseases appear to be more
      closely related to their proximity to QENP than their proximity to anthrax
      outbreaks. Neither risk factor had a strong effect on knowledge of disease, nor
      any effect on behaviors associated with disease response or control. Instead,
      participants reported that social pressures, the economics of poverty, and the
      lack of health and veterinary infrastructure highly influenced responses to
      disease. The complex connections between the social needs and the economic
      context of these communities seem to be undermining current anthrax control and
      education measures. This livelihood-based decision-making may be unlikely to
      respond to educational intervention alone. This study provides a strong base for
      further research and for improvements in effective disease control. 

PMID- 25066947
TI  - The inter-section of political history and health policy in Asia--the historical
      foundations for health policy analysis.
AB  - One of the challenges for health reform in Asia is the diverse set of socio
      economic and political structures, and the related variability in the direction
      and pace of health systems and policy reform. This paper aims to make comparative
      observations and analysis of health policy reform in the context of historical
      change, and considers the implications of these findings for the practice of
      health policy analysis. We adopt an ecological model for analysis of policy
      development, whereby health systems are considered as dynamic social constructs
      shaped by changing political and social conditions. Utilizing historical, social
      scientific and health literature, timelines of health and history for five
      countries (Cambodia, Myanmar, Mongolia, North Korea and Timor Leste) are mapped
      over a 30-50 year period. The case studies compare and contrast key turning
      points in political and health policy history, and examines the manner in which
      these turning points sets the scene for the acting out of longer term health
      policy formation, particularly with regard to the managerial domains of health
      policy making. Findings illustrate that the direction of health policy reform is
      shaped by the character of political reform, with countries in the region being
      at variable stages of transition from monolithic and centralized administrations,
      towards more complex management arrangements characterized by a diversity of
      health providers, constituency interest and financing sources. The pace of reform
      is driven by a country's institutional capability to withstand and manage
      transition shocks of post conflict rehabilitation and emergence of liberal
      economic reforms in an altered governance context. These findings demonstrate
      that health policy analysis needs to be informed by a deeper understanding and
      questioning of the historical trajectory and political stance that sets the stage
      for the acting out of health policy formation, in order that health systems
      function optimally along their own historical pathways. 

PMID- 25066949
TI  - The local atomic structures of liquid CO at 3.6 GPa and polymerized CO at 0 to 30
      GPa from high-pressure pair distribution function analysis.
AB  - The local atomic structures of liquid and polymerized CO and its decomposition
      products were analyzed at pressures up to 30 GPa in diamond anvil cells by X-ray
      diffraction, pair distribution function (PDF) analysis, single-crystal
      diffraction, and Raman spectroscopy. The structural models were obtained by
      density functional calculations. Analysis of the PDF of a liquid CO-rich phase
      revealed that the local structure has a pronounced short-range order. The PDFs of
      polymerized amorphous CO at several pressures revealed the compression of the
      molecular structure; covalent bond lengths did not change significantly with
      pressure. Experimental PDFs could be reproduced with simulations from DFT
      optimized structural models. Likely structural features of polymerized CO are
      thus 4- to 6-membered rings (lactones, cyclic ethers, and rings decorated with
      carbonyl groups) and long bent chains with carbonyl groups and bridging atoms.
      Laser heating polymerized CO at pressures of 7 to 9 GPa and 20 GPa resulted in
      the formation of CO(2).

PMID- 25066950
TI  - Telemedicine--a bibliometric and content analysis of 17,932 publication records.
AB  - OBJECTIVES: We aimed to provide an up-to-date contemporary bibliometric view of
      the telemedicine and telehealth literature and a longitudinal analysis of changes
      in content themes. METHODS: Software tools were used to extract and process
      MEDLINE entries. Frequencies of papers by year of publication and outlet were
      calculated, ranked, charted and tabulated. Frequency of publication by author was
      also calculated, ranked and tabulated. The process was repeated for two time
      periods to examine change: (i) 1970-1995 and (ii) 2009-2013. Content analysis of
      abstracts was conducted and tag clouds were generated. This visual representation
      was used to identify key words and prominent themes. RESULTS: 17,932 records
      relating to articles published in 2523 unique outlets were analyzed. In the
      cumulative literature, 3152 (18%) articles were published in specialist
      telemedicine journals while most articles (14,780 [82%]) were published in
      mainstream outlets. This pattern was observed in both epochs. Clinical journals
      were not highly represented. Over time 46,066 unique authors have contributed to
      the field, with 21,109 of them publishing in the period 2009-2013. DISCUSSION:
      Telemedicine is a large and growing field with most publication occurring outside
      of the specialist journals. Content analysis suggested a change of focus from the
      technical to the clinical between the two epochs. As a healthcare setting, the
      home also appears to be emergent. CONCLUSION: This study updates the findings of
      previous studies. The emphasis within the literature suggests a move from
      technical issues to clinical applications and evaluation. The maturity of the
      field and its accessibility to clinicians and policy makers remains unclear.

PMID- 25066948
TI  - Circadian rest-activity rhythms predict future increases in depressive symptoms
      among community-dwelling older men.
AB  - OBJECTIVE: Circadian rest-activity rhythms (CARs) have been cross-sectionally
      associated with depressive symptoms, although no longitudinal research has
      examined whether CARs are a risk factor for developing depressive symptoms.
      METHODS: We examined associations of CARs (measured with actigraphy over a mean
      of 4.8 days) with depressive symptoms (measured with the Geriatric Depression
      Scale) among 2,892 community-dwelling older men (mean age: 76.2 +/- 5.5 years)
      from the MrOS Sleep Study who were without cognitive impairment. Among 2,124 men
      with minimal (0-2) symptoms at baseline, we assessed associations between CAR
      parameters and increases to mild (3-5) or clinically significant (>=6) symptoms
      after an average of 1.2 (+/-0.32) years. RESULTS: Cross-sectional associations
      between rhythm height parameters were independent of chronic diseases, lifestyle,
      sleep, and self-reported physical activity covariates. For example, men in the
      lowest mesor quartile had twice the adjusted odds (adjusted odds ratio [AOR]:
      2.04, 95% confidence interval [CI]: 1.36-3.04, p = 0.0005) of having prevalent
      clinically significant symptoms (compared to minimal). Longitudinally, low CAR
      robustness (being in the lowest quartile of the pseudo-F statistic) was
      independently associated with increasing odds of developing symptoms (i.e., AOR
      for having clinically significant depressive symptoms at follow-up = 2.58, 95%
      CI: 1.11-5.99, p = 0.03). CONCLUSION: CAR disturbances are indicative of
      depressive symptomology. Low CAR robustness may independently contribute to the
      risk of worsening depression symptomology.

PMID- 25066951
TI  - Inadequate vancomycin therapy in term and preterm neonates: a retrospective
      analysis of trough serum concentrations in relation to minimal inhibitory
      concentrations.
AB  - BACKGROUND: Vancomycin is effective against gram-positive bacteria and the first
      line antibiotic for treatment of proven coagulase-negative staphylococcal
      infections. The aim of this study is bipartite: first, to assess the percentage
      of therapeutic initial trough serum concentrations and second, to evaluate the
      adequacy of the therapeutic range in interrelationship with the observed MIC
      values in neonates. METHODS: In this study, preterm and term neonates admitted at
      a tertiary NICU in the Netherlands from January 2009 to December 2012 and treated
      with vancomycin for a proven gram-positive infection were included. Trough serum
      concentrations were measured prior to administration of the 5th dose. Trough
      concentrations in the range of 10 to 15 mg/L were considered therapeutic.
      Staphylococcal species minimal inhibitory concentrations (MIC's) were determined
      using the E-test method. Species identification was performed by matrix-assisted
      laser desorption/ionisation mass spectrometry. RESULTS: Of the 112 neonates, 53
      neonates (47%) had sub-therapeutic initial trough serum concentrations of
      vancomycin, whereas 22% had supra-therapeutic initial trough serum
      concentrations. In all patients doses were adjusted on basis of the initial
      trough concentration. In 40% (23/57) of the neonates the second trough
      concentration remained sub-therapeutic. MIC's were determined for 30 coagulase
      negative Staphylococcus isolates obtained from 19 patients. Only 4 out of 19
      subjects had a trough concentration greater than tenfold the MIC. CONCLUSIONS:
      Forty-seven percent of the neonates had sub-therapeutic initial trough serum
      concentrations of vancomycin. The MIC-data indicate that the percentages of
      underdosed patients may be greater. It may be advisable to increase the lower
      limit of the therapeutic range for European neonates.

PMID- 25066952
TI  - Five new quassinoids and cytotoxic constituents from the roots of Eurycoma
      longifolia.
AB  - Eurycoma longifolia has been widely used for various traditional medicinal
      purposes in South-East Asia. In this study, five new quassinoids, eurylactone E
      (1), eurylactone F (2), eurylactone G (3), eurycomalide D (4), and eurycomalide E
      (5), along with ten known quassinoids (6-15) were isolated from the roots of E.
      longifolia. Their structures were determined by extensive spectroscopic methods,
      including 1D and 2D NMR, and MS spectra data. Among the isolated compounds,
      13beta-methyl,21-dihydroeurycomanone (6) has been reported as a synthetic
      derivative. However, it was isolated from the natural product for the first time
      in this study. The cytotoxic activities of fifteen compounds were evaluated
      against human lung cancer cell line, A549 and human cervical cancer cell line,
      HeLa. 

PMID- 25066953
TI  - In silico and pharmacological screenings identify novel serine racemase
      inhibitors.
AB  - D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate
      receptor and its biosynthesis is catalyzed by serine racemase (SR). The
      overactivation of the NMDA receptor has been implicated in the development of
      neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors
      of SR have potential against these pathological states. Here, we have developed
      novel inhibitors of SR by in silico screening and in vitro enzyme assay. The
      newly developed inhibitors have lower IC50 value comparing with that of malonate,
      one of the standard SR inhibitor. The structural features of novel inhibitors
      suggest the importance of central amide structure having a phenoxy substituent in
      their structure for the SR inhibitory activity. The present findings suggest the
      importance and rational development of new drugs for diseases of NMDAR
      overactivation.

PMID- 25066954
TI  - Intravenous corticosteroids in moderately active ulcerative colitis refractory to
      oral corticosteroids.
AB  - BACKGROUND: Oral corticosteroids remain the mainstay of treatment for moderately
      active ulcerative colitis (UC). In patients who fail to respond to oral
      corticosteroids, attempting the intravenous route before starting rescue
      therapies is an alternative, although no evidence supports this strategy. AIM: To
      evaluate clinical outcomes after a course of intravenous corticosteroids for
      moderate attacks of UC according to the failed oral corticosteroids or not.
      METHODS: All episodes of active UC admitted to three university hospitals between
      January 2005 and December 2011 were identified and retrospectively reviewed. Only
      moderately active episodes treated with intravenous corticosteroids were
      included. Treatment outcome was compared between episodes which failed to
      outpatient oral corticosteroids for the index flare and those directly treated by
      intravenous corticosteroids. RESULTS: 110 episodes were included, 45% of which
      failed to outpatient oral corticosteroids (median dose 60mg/day [IQR 50-60],
      median length of course 10days [IQR 7-17]). Initial response (defined as mild
      severity or inactive disease at day 7 after starting intravenous corticosteroids,
      without rescue therapy) was achieved in 75%, with no between-group differences
      (78% vs. 75%). After a median follow-up of 12months (IQR 4-24), 35% of the
      initial responders developed steroid-dependency and up to 13% required colectomy.
      Unsuccessful response to oral corticosteroids was the only factor associated with
      steroid-dependency in the long term (P=0.001). CONCLUSIONS: Intravenous
      corticosteroids are efficient for inducing remission in moderately active UC
      unresponsive to oral corticosteroids, but almost half of these patients develop
      early steroid-dependency. Alternative therapeutic strategies should be assessed
      in this clinical setting.

PMID- 25066955
TI  - Structural and functional analysis show that the Escherichia coli uncharacterized
      protein YjcS is likely an alkylsulfatase.
AB  - Sodium dodecyl sulfate (SDS) is a widely used anionic surfactant in industry and
      research settings, and is known to have a detrimental effect to the environment.
      The pathway of SDS degradation by bacteria is initiated by an alkylsulfatase and
      the oxidized product, 1-dodecanoic acid, subsequently enters into the beta
      oxidation pathway and is used as a carbon source. In this work, we solved the
      crystal structure of Escherichia coli uncharacterized protein YjcS and identified
      that it belongs to the Type III alkylsulfatase with a signal peptide (residues 1
      29) at the N terminus. YjcS hydrolyzed SDS and the double mutant D184N-H185A
      located in the conserved HXHXDH catalytic motif abolished this activity.

PMID- 25066956
TI  - The development of sustainable emergency care in ghana: physician, nursing and
      prehospital care training initiatives.
AB  - BACKGROUND: Ghana's first Emergency Medicine residency and nursing training
      programs were initiated in 2009 and 2010, respectively, at Komfo Anokye Teaching
      Hospital in the city of Kumasi in association with Kwame Nkrumah University of
      Science and Technology and the Universities of Michigan and Utah. In addition,
      the National Ambulance Service was commissioned initially in 2004 and has
      developed to include both prehospital transport services in all regions of the
      country and Emergency Medical Technician training. Over a decade of domestic and
      international partnership has focused on making improvements in emergency care at
      a variety of institutional levels, culminating in the establishment of
      comprehensive emergency care training programs. OBJECTIVE: We describe the
      history and status of novel postgraduate emergency physician, nurse, and
      prehospital provider training programs as well as the prospect of creating a
      board certification process and formal continuing education program for
      practicing emergency physicians. DISCUSSION: Significant strides have been made
      in the development of emergency care and training in Ghana over the last decade,
      resulting in the first group of Specialist-level emergency physicians as of late
      2012, as well as development of accredited emergency nursing curricula and
      continued expansion of a national Emergency Medical Service. CONCLUSION: This
      work represents a significant move toward in-country development of sustainable,
      interdisciplinary, team-based emergency provider training programs designed to
      retain skilled health care workers in Ghana and may serve as a model for similar
      developing nations.

PMID- 25066957
TI  - Spatial distribution of theobromine--a low MW drug--in tissues via matrix-free
      NALDI-MS imaging.
AB  - The ability of nano-assisted laser desorption-ionization mass spectrometry
      imaging (NALDI-IMS) to provide selective chemical monitoring with appropriate
      spatial distribution of a low molecular drug in a biological tissue was
      investigated. NALDI-IMS is a matrix-free laser desorption ionization (LDI)
      protocol based on imprinting of tissue constituents on a nanostructured surface.
      Using the accumulation of theobromine in rat kidney as a model, NALDI-IMS was
      found to provide well-resolved images of the special distribution of this low
      molecular weight (MW) drug in tissue.

PMID- 25066958
TI  - Preparation of patterned ultrathin polymer films.
AB  - Though patterned ultrathin polymer films (<100 nm) are of great importance in the
      fields of sensors and nanoelectronic devices, the fabrication of patterned
      ultrathin polymer films remains a great challenge. Herein, patterned ultrathin
      polymer films are fabricated facilely on hydrophobic substrates with different
      hydrophilic outline patterns by the pinning of three-phase contact lines of
      polymer solution on the hydrophilic outlines. This method is universal for most
      of the water-soluble polymers, and poly(vinyl alcohol) (PVA) has been selected as
      a model polymer due to its biocompatibility and good film-forming property. The
      results indicate that the morphologies of ultrathin polymer films can be
      precisely adjusted by the size of the hydrophilic outline pattern. Specifically,
      patterned hydrophilic outlines with sizes of 100, 60, and 40 MUm lead to the
      formation of concave-shaped ultrathin PVA films, whereas uniform ultrathin PVA
      films are formed on 20 and 10 MUm patterned substrates. The controllabilities of
      morphologies can be interpreted through the influences of the slip length and
      coffee ring effect. Theoretical analysis shows that when the size of the
      hydrophilic outline patterns is smaller than a critical value, the coffee ring
      effect disappears and uniform patterned ultrathin polymer films can be formed for
      all polymer concentrations. These results provide an effective methodology for
      the fabrication of patterned ultrathin polymer films and enhance the
      understanding of the coffee ring effect. 

PMID- 25066960
TI  - Emotional hyper-reactivity in borderline personality disorder is related to
      trauma and interpersonal themes.
AB  - Heightened emotional reactivity is one of the core features of borderline
      personality disorder (BPD). However, recent findings could not provide evidence
      for a general emotional hyper-reactivity in BPD. The present study examines the
      emotional responding to self-relevant pictures in dependency of the thematic
      category (e.g., trauma, interpersonal interaction) in patients with BPD.
      Therefore, women with BPD (n=31), women with major depression disorder (n=29) and
      female healthy controls (n=33) rated pictures allocated to thematically different
      categories (violence, sexual abuse, interaction, non-suicidal self-injury, and
      suicide) regarding self-relevance, arousal, valence and the urge of non-suicidal
      self-injury. Compared to both control groups, patients with BPD reported higher
      self-relevance regarding all categories, but significantly higher emotional
      ratings only for pictures showing sexual abuse and interpersonal themes. In
      addition, patients with BPD and comorbid posttraumatic stress disorder showed
      higher emotional reactivity in violence pictures. Our data provide clear evidence
      that patients with BPD show a specific emotional hyper-reactivity with respect to
      schema-related triggers like trauma and interpersonal situations. Future studies
      are needed to investigate physiological responses to these self-relevant themes
      in patients with BPD. 

PMID- 25066961
TI  - Smell identification in individuals at clinical high risk for schizophrenia.
AB  - Smell identification deficits exist in schizophrenia, and may be associated with
      its negative symptoms. Less is known about smell identification and its clinical
      correlates in individuals at clinical high risk (CHR) for schizophrenia and
      related psychotic disorders. We examined smell identification, symptoms and IQ in
      71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell
      identification was assessed using both the 40-item University of Pennsylvania
      Smell Identification Test (UPSIT; Doty, R.L., Shaman, P., Kimmelman, C.P., Dann,
      M.S., 1984. University of Pennsylvania Smell Identification Test: a rapid
      quantitative olfactory function test for the clinic. Laryngoscope 94, 176-178)
      and its extracted 12-item Brief Smell Identification Test (Goudsmit, N., Coleman,
      E., Seckinger, R.A., Wolitzky, R., Stanford, A.D., Corcoran, C., Goetz, R.R.,
      Malaspina, D., 2003. A brief smell identification test discriminates between
      deficit and non-deficit schizophrenia. Psychiatry Research 120, 155-164). Smell
      identification did not significantly differ between CHR subjects and controls.
      Among CHR subjects, smell identification did not predict schizophrenia (N=19;
      27%) within 2 years, nor was it associated with negative or positive symptoms.
      This is the third prospective cohort study to examine smell identification in CHR
      subjects, and overall, findings are inconclusive, similar to what is found for
      other disorders in adolescents, such as autism spectrum, attention deficit and
      anxiety disorders. Smell identification deficit may not have clear utility as a
      marker of emergent schizophrenia and related psychotic disorders. 

PMID- 25066962
TI  - Artifactual effect of propofol on ECT peak heart rate.

PMID- 25066963
TI  - Author's reply.

PMID- 25066964
TI  - Affective and cognitive empathy and social quality of life in schizophrenia: a
      comparison between a parallel process model and an integrative meditation model.
AB  - Two alternative models of impaired cognitive and affective processing that may
      underlie reduced social quality of life (SQoL) of persons with schizophrenia,
      were examined. According to the parallel process model, impaired cognitive
      empathy and affective empathy make relatively independent contributions to the
      symptoms of schizophrenia and to the consequent reduction in SQoL. According to
      the integrative mediation model, the symptoms of schizophrenia and the reduction
      in SQoL associated with these symptoms are the products of a process by which
      impairments of cognitive empathy are contingent on impairments of affective
      empathy. 90 persons with schizophrenia were assessed for SQoL, symptoms and
      cognitive and affective empathy. Results support the integrative mediation model
      only for cognitive empathy and negative psychiatric symptoms. Only the negative
      links between cognitive empathy and negative symptoms served to mediate the
      positive relation between affective empathy and SQoL. Positive symptoms had a
      limited negative impact on SQoL and did not play a role in the paths that linked
      affective empathy to SQoL. Age had a statistically significant and negative
      indirect relationship to SQoL. Results are consistent with recent approach that
      distinguish between cognitive and affective empathy and specify how these two
      processes are integrated. 

PMID- 25066965
TI  - Relationship between asymmetric dimethylarginine and nocturia in the general
      elderly population: The HEIJO-KYO cohort.
AB  - AIMS: To evaluate the relationship between asymmetric dimethylarginine (ADMA) and
      nocturia. METHODS: A total of 862 community-based elderly individuals were
      examined in this cross-sectional study (mean age, 72.1 years). We measured
      nocturnal void frequency and serum ADMA levels. Nocturia was ascertained for a
      frequency of two or more nocturnal voids. RESULTS: Nocturia was observed in 262
      (30.4%) participants. Univariate logistic regression models revealed a
      significant association between prevalent nocturia and ADMA levels (crude odds
      ratio [OR], 1.556 [2nd vs. 1st tertile]; 95% confidence interval [CI], 1.066
      2.270; P = 0.022; crude OR, 2.114 [3rd vs. 1st tertile]; 95% CI, 1.453-3.072; P <
      0.001). Univariate logistic regression models also revealed marginal to
      significant associations between prevalent nocturia and age, gender, calcium
      channel blocker use, nitric oxide-related drug use, diabetes, estimated
      glomerular filtration rate, insomnia, benign prostatic hyperplasia, overnight
      urine volume, and endogenous melatonin levels. In the multivariate model
      simultaneously adjusted for the former variables, higher ADMA levels were
      significantly associated with higher OR for nocturia (adjusted OR, 1.556 [3rd vs.
      1st tertiles]; 95% CI, 1.010-2.397; P = 0.045). CONCLUSION: Serum ADMA levels, an
      endogenous inhibitor of nitric oxide synthase, are significantly associated with
      prevalent nocturia in the general elderly population.

PMID- 25066966
TI  - Detection and analysis of recombination in GII.4 norovirus strains causing
      gastroenteritis outbreaks in Alberta.
AB  - Recombination is an important mechanism generating genetic diversity in norovirus
      (NoV) that occurs commonly at the NoV polymerase-capsid (ORF1/2) junction. The
      genotyping method based on partial ORF2 sequences currently used to characterize
      circulating NoV strains in gastroenteritis outbreaks in Alberta cannot detect
      such recombination events and provides only limited information on NoV genetic
      evolution. The objective of this study was to determine whether any NoV GII.4
      strains causing outbreaks in Alberta are recombinants. Twenty stool samples
      collected during outbreaks occurring between July 2004 and January 2012 were
      selected to include the GII.4 variants Farmington Hills 2002, Hunter 2004,
      Yerseke 2006a, Den Haag 2006b, Apeldoorn 2007, New Orleans 2009, and Sydney 2012
      based on previous NoV ORF2-genotyping results. Near full-length NoV genome
      sequences were obtained, aligned with reference sequences from GenBank and
      analyzed with RDPv4.13. Two sequences corresponding to Apeldoorn 2007, and Sydney
      2012 were identified as recombinants with breakpoints near the ORF1/2 junction
      and putative parental strains as previously reported. We also identified, for the
      first time, a non-recombinant sequence resembling the ORF2-3 parent of the
      recombinant cluster Sydney 2012 responsible for the most recent pandemic. Our
      results confirmed the presence of recombinant NoV GII.4 strains in Alberta, and
      highlight the importance of including additional genomic regions in surveillance
      studies to trace the evolution of pandemic NoV GII.4 strains. 

PMID- 25066967
TI  - Reply: To PMID 24123276.

PMID- 25066968
TI  - Hemocyte morphology and phagocytic activity in the common cuttlefish (Sepia
      officinalis).
AB  - Little is known about the immune system of cephalopods, in spite of their many
      highly derived characters within the molluscan clade, including a vertebrate-like
      high-pressure closed circulatory system. Further the economic importance of
      cephalopod fisheries, potential for aquaculture, and use as ecotoxicology models
      demand a thorough understanding of their immune system. In this study, we present
      a comprehensive characterization of hemocytes in the common cuttlefish Sepia
      officinalis. Cytological stainings, electron microscopy- and flow cytometry
      observations highlight a single granulocyte population with various densities of
      eosinophilic granules and unstained vesicles. These hemocytes contain acid
      phosphatase-, lysozyme- and proPO system enzymes, and have high activity in bead
      phagocytosis assays. Interestingly, bead pre-incubation in plasma results in time
      dependent aggregation perhaps resulting from hemocyanin-coating, and decrease in
      phagocytosis. This study provides the basis for understanding hemocyte-mediated
      immunity in the common cuttlefish, and essential background for future studies on
      cephalopod immunity. 

PMID- 25066969
TI  - [Proceedings of the Congress of the French Society of Pediatrics, 15-17 May,
      2013, Lyon, France].

PMID- 25067789
TI  - Chromatin regulators in neurodevelopment and disease: Analysis of fly neural
      circuits provides insights: Networks of chromatin regulators and transcription
      factors underlie Drosophila neurogenesis and cognitive defects in intellectual
      disability and neuropsychiatric disorder models.
AB  - Disruptions in chromatin regulator genes are frequently the cause of
      neurodevelopmental and neuropsychiatric disorders. Chromatin regulators are
      widely expressed in the brain, yet symptoms suggest that specific circuits can be
      preferentially altered when they are mutated. Using Drosophila allows targeted
      manipulation of chromatin regulators in defined neuronal classes, lineages, or
      circuits, revealing their roles in neuronal precursor self-renewal, dendrite and
      axon targeting, neuron diversification, and the tuning of developmental signaling
      pathways. Phenotypes arising from chromatin regulator disruption are context
      dependent - defined by interaction networks between the regulators, transcription
      factors, and chromatin remodeling complex partners. Future challenges are to
      determine the complexity of partner interactions, and to ascertain the degree to
      which cognitive deficits are due to loss of chromatin regulator activity in
      building a circuit or in maintaining homeostasis and activity within it. 

PMID- 25067787
TI  - Senescence induction in renal carcinoma cells by Nutlin-3: a potential
      therapeutic strategy based on MDM2 antagonism.
AB  - Although the role of p53 as a tumour suppressor in renal cell carcinoma (RCC) is
      unclear, our recent analysis suggests that increased wild-type p53 protein
      expression is associated with poor outcome. A growing body of evidence also
      suggests that p53 expression and increased co-expression of MDM2 are linked with
      poor prognosis in RCC. We have therefore examined whether an MDM2 antagonist;
      Nutlin-3, might rescue/increase p53 expression and induce growth inhibition or
      apoptosis in RCC cells that retain wild-type p53. We show that inhibition of p53
      suppression by MDM2 in RCC cells promotes growth arrest and p53-dependent
      senescence - phenotypes known to mediate p53 tumour suppression in vivo. We
      propose that future investigations of therapeutic strategies for RCC should
      incorporate MDM2 antagonism as part of strategies aimed at rescuing/augmenting
      p53 tumour suppressor function. 

PMID- 25067788
TI  - Targeting the C-terminal focal adhesion kinase scaffold in pancreatic cancer.
AB  - Preliminary studies in our laboratory have demonstrated the importance of both
      the NH2 and COOH terminus scaffolding functions of focal adhesion kinase (FAK).
      Here, we describe a new small molecule inhibitor, C10, that targets the FAK C
      terminus scaffold. C10 showed marked selectivity for cells overexpressing VEGFR3
      when tested in isogenic cell lines, MCF7 and MCF7-VEGFR3. C10 preferentially
      inhibited pancreatic tumor growth in vivo in cells with high FAK-Y925 and VEGFR3
      expression. Treatment with C10 led to a significant inhibition in endothelial
      cell proliferation and tumor endothelial and lymphatic vessel density and
      decrease in interstitial fluid pressure. These results highlight the underlying
      importance of targeting the FAK scaffold to treat human cancers. 

PMID- 25067790
TI  - Can a lifestyle intervention improve physical fitness in adolescents and young
      adults with spastic cerebral palsy? A randomized controlled trial.
AB  - OBJECTIVE: To evaluate both the short- and long-term effectiveness of a lifestyle
      intervention on physical fitness in adolescents and young adults with cerebral
      palsy (CP). DESIGN: Single-blind, randomized controlled trial. SETTING:
      University hospitals and rehabilitation clinics. PARTICIPANTS: Adolescents and
      young adults (N=57) with spastic CP classified in Gross Motor Function
      Classification System levels I through IV; of these, 42 completed the study.
      INTERVENTION: A 6-month lifestyle intervention consisting of physical fitness
      training combined with counseling sessions focused on physical behavior and
      sports participation. MAIN OUTCOME MEASURES: Physical fitness, including measures
      of cardiopulmonary fitness, muscle strength, and body composition. RESULTS:
      Favorable short- and medium-term effects were found for peak oxygen consumption,
      oxygen consumption, and load on the anaerobic threshold and waist circumference.
      Favorable long-term effects were found for sum of skinfolds, systolic blood
      pressure, and total cholesterol. CONCLUSIONS: This exploratory study showed that
      the lifestyle intervention was effective in improving cardiopulmonary fitness and
      body composition. Effects of body composition were maintained in the long term.
      However, the intervention needs to be optimized to increase muscle strength and
      for long-term retention of effects on aerobic capacity.

PMID- 25067791
TI  - Dyskeratosis congenita caused by a novel TERT point mutation in siblings with
      pancytopenia and exudative retinopathy.
AB  - Two siblings presenting with exudative retinopathy, thrombocytopenia, and
      macrocytosis were found to have markedly shortened telomeres and a previously
      unreported inherited mutation in TERT, c.2603A>G. Revesz syndrome, a subtype of
      dyskeratosis congenita (DC) caused by TINF2 mutation, combines marrow failure
      with exudative retinopathy, intracranial calcifications, and neurocognitive
      impairment. As our patients manifested neither intracranial calcification nor
      significant neurocognitive impairment, we conclude that the c.2603A>G TERT
      mutation may define a subtype of DC manifesting first as exudative retinopathy
      without other signs of DC. Children with exudative retinopathy should be
      periodically screened for macrocytosis and cytopenias to evaluate for underlying
      DC.

PMID- 25067792
TI  - Effect of anion structures on cholinium ionic liquids pretreatment of rice straw
      and the subsequent enzymatic hydrolysis.
AB  - In this work, 28 cholinium ionic liquids (ILs), most of which are good solvents
      for dissolving lignin, were used for rice straw pretreatment to improve
      subsequent enzymatic hydrolysis. The anion exerted a significant effect on the
      pretreatment effectiveness of the IL as well as the subsequent enzymatic
      hydrolysis efficiency of rice straw residues. The presence of the basic group(s)
      in the anion significantly enhanced the IL pretreatment effectiveness, while the
      carboxyl, hydroxyl and aromatic groups had a negative impact on IL
      delignification. Except for amino acid-based ILs, the delignification abilities
      of the ILs are linearly and positively correlated with the pKa values of the
      conjugate acids of the anions. Of the ILs tested, amino acid-based ILs,
      especially basic amino acid-based ILs, are the most effective pretreatment
      solvents. Satisfactory reducing sugar yields (81% for glucose and 26% for xylose)
      were obtained in the enzymatic hydrolysis of rice straw pretreated by cholinium
      argininate ([Ch][Arg]) under a pretty mild pretreatment severity (60 degrees C, 6
      h). The results presented in this work may be useful for rational design of novel
      and green ILs for delignification of lignocellulose.

PMID- 25067793
TI  - Multiple site-specific installations of Nepsilon-monomethyl-L-lysine into histone
      proteins by cell-based and cell-free protein synthesis.
AB  - Lysine methylation is one of the important post-translational modifications of
      histones, and produces an N(epsilon) -mono-, di-, or trimethyllysine residues.
      Multiple and site-specific lysine methylations of histones are essential to
      define epigenetic statuses and control heterochromatin formation, DNA repair, and
      transcription regulation. A method was previously developed to build an analogue
      of N(epsilon)-monomethyllysine, with cysteine substituting for lysine. Here, we
      have developed a new method of preparing histones bearing multiple N(epsilon)
      monomethyllysine residues at specified positions. Release factor 1-knockout
      (RFzero) Escherichia coli cells or a cell-free system based on the RFzero cell
      lysate was used for protein synthesis, as in RFzero cells UAG is redefined as a
      sense codon for non-canonical amino acids. During protein synthesis, a tert
      butyloxycarbonyl-protected N(epsilon)-monomethyllysine analogue is ligated to
      Methanosarcina mazei pyrrolysine tRNA (tRNA(Pyl)) by M. mazei pyrrolysyl-tRNA
      synthetase mutants, and is translationally incorporated into one or more
      positions specified by the UAG codon. Protecting groups on the protein are then
      removed with trifluoroacetic acid to generate N(epsilon)-monomethyllysine
      residues. We installed N(epsilon)-monomethyllysine residues at positions 4, 9,
      27, 36, and/or 79 of human histone H3. Each of the N(epsilon)-monomethyllysine
      residues within the produced histone H3 was recognized by its specific antibody.
      Furthermore, the antibody recognized the authentic N(epsilon)-monomethyllysine
      residue at position 27 better than the N(epsilon)-monomethyllysine analogue built
      with cysteine. Mass spectrometry analyses also confirmed the lysine modifications
      on the produced histone H3. Thus, our method enables the installation of
      authentic N(epsilon)-monomethyllysines at multiple positions within a protein for
      large-scale production.

PMID- 25067794
TI  - What do midwives fear?
AB  - BACKGROUND: There is evidence that a significant number of women are fearful
      about birth but less is known about the fears of maternity health providers and
      how their fear may impact on the women they care for. AIM: The aim of this study
      was to determine the top fears midwives in Australia and New Zealand hold when it
      comes to caring for childbearing women. METHOD: From 2009 to 2011, 17 workshops
      were held in Australia and New Zealand supporting over 700 midwives develop
      skills to keep birth normal. During the workshop midwives were asked to write
      their top fear on a piece of paper and return it to the presenters. Similar
      concepts were grouped together to form 8 major categories. FINDINGS: In total 739
      fears were reported and these were death of a baby (n=177), missing something
      that causes harm (n=176), obstetric emergencies (n=114), maternal death (n=83),
      being watched (n=68), being the cause of a negative birth experience (n=52),
      dealing with the unknown (n=36) and losing passion and confidence around normal
      birth (n=32). Student midwives were more concerned about knowing what to do,
      while homebirth midwives were mostly concerned with being blamed if something
      went wrong. CONCLUSION: There was consistency between the 17 groups of midwives
      regarding top fears held. Supporting midwives with workshops such as dealing with
      grief and loss and managing fear could help reduce their anxiety. Obstetric
      emergency skills workshops may help midwives feel more confident, especially
      those dealing with shoulder dystocia and PPH as they were most commonly recorded.

PMID- 25067795
TI  - Crazy for Ya Ba: methamphetamine use among northern Thai youth.
AB  - BACKGROUND: Since the mid-1990s, Thailand has been one of the largest per capita
      consumers of methamphetamine pills (ya ba - "crazy drug") in the world and one of
      the leading consumers of methamphetamine in Southeast Asia, with its youth
      comprising the majority of users. This article examines the socio-cultural
      context of methamphetamine use among young Thai in order to understand its
      widespread appeal. METHODS: The study is based on 18 months of ethnographic
      research in Chiang Mai, northern Thailand, between 2002 and 2006 and a follow-up
      field trip in 2011. In-depth interviews were carried out with 211 young people
      aged between 15 and 25 in institutional and non-institutional settings. Many of
      the findings derive from participant observation and informal interviews with a
      small sample of 20 people. RESULTS: Chiang Mai youth have transformed
      methamphetamine from a labourers' drug centred on economic utility to a multi
      purpose youth drug primarily consumed for pleasure and performance. Ya ba appeals
      to many young Thai due to its positive image as a modern and fashionable consumer
      commodity, with confidence in these synthetic pills drawing on and mirroring a
      broader faith in modern (western) medicine. CONCLUSION: The growing demand for ya
      ba in northern Thailand is in part a reflection of the changing social values
      that have accompanied rapid urbanisation and modernisation in Thailand. In their
      overwhelming aspiration to be modern, young Thai are consuming ya ba not to rebel
      against the dominant culture, but to keep up with the demands and expectations of
      a modern capitalist society.

PMID- 25067796
TI  - Anatomical eponyms, Part 2: The other side of the coin.
AB  - Over a century after they were removed, at least officially, from anatomical
      terminology, eponyms remain an obviously controversial topic. In the first part
      of this paper we acted as their defense counsel, aiming to demonstrate that the
      1895 first edition of the Nomina Anatomica and subsequently the Federative
      Committee on Anatomical Terminology (FCAT) probably put the cart before the
      horse. However, their authors advanced arguments supporting their decision, and
      it is now time to develop these arguments. Let us now become the public
      prosecutor of eponyms.

PMID- 25067797
TI  - Boveri at 100: the life and times of Theodor Boveri.
AB  - This perspective focuses on the life and personality of TH Boveri, who was one of
      the leading creative and visionary scientists of the second half of the
      nineteenth century. Born in Bamberg in 1862, he made his scientific career in
      Munich and Wurzburg, where he produced his prolific and important research,
      including seminal papers on cytogenetics. Of particular note is his work on
      chromosomal structures and function, including a theory of meiosis, a field
      almost new at that time. From these studies he created a theoretical model on
      oncogenesis, Zur Frage der Entstehung maligner Tumoren, which was originally
      published in 1914. Boveri's personality was characterized by an active and
      sometimes turbulent temperament, which nevertheless was controlled by scientific
      objectivity and doubts about his own abilities, at least with regard to his
      research. These characteristics made him an outstanding scientist who contributed
      new knowledge to the world of biology and pathology.

PMID- 25067798
TI  - Predictors of urinary continence following tethered cord release in children with
      occult spinal dysraphism.
AB  - OBJECTIVE: Children with occult spinal dysraphism represent a wide spectrum of
      patients. Previous studies assessing urologic outcomes have in part been
      deficient due to the inability to appropriately categorize these patients and
      gather long-term follow-up data. In this study, a uniform set of patients that
      had occult spinal dysraphism with magnetic resonance imaging findings of a fatty
      filum terminale (FF) and/or low-lying cord (LLC) was identified. Utilizing long
      term follow-up data, predictors for achieving urinary continence following
      tethered cord release (TCR) were determined. METHODS: A retrospective chart
      review of pediatric patients with a diagnosis of tethered cord who underwent TCR
      from 1995 to 2005 was performed. Analysis was limited to patients who had primary
      TCR by one of two neurosurgeons within our multidisciplinary spina bifida clinic,
      who had greater than 1-year follow-up, and who were old enough to have continence
      status assessed (age > 6 years unless definitively toilet trained earlier).
      Patients with other associated forms of spinal dysraphism (lipomyelomeningeocele,
      spinal lipomas, sacral agenesis), anorectal malformations, and genitourinary
      anomalies were excluded. Pre- and post-TCR urodynamics, radiographic studies,
      functional orthopedic status, and urologic outcomes were assessed. Urodynamic
      results were categorized by three blinded urologists into one of three urodynamic
      patterns: (1) normal, (2) indeterminate, and (3) high risk. RESULTS: A total of
      147 patients with FF and/or LLC that underwent TCR were reviewed. 51 patients
      were excluded because of another associated spinal dysraphism (15/51 patients) or
      an anorectal/genitourinary anomaly (36/51 patients). Fifty-nine of the remaining
      96 patients had adequate long-term follow-up data to be included in the study. 20
      patients were asymptomatic at the time of TCR while 39 presented with orthopedic
      and/or urologic symptoms. The average age at surgery was 59.3 months (range 2-277
      months) with an average follow-up of 7.0 years (range 1-16 years). At latest
      follow-up, 47 (80%) patients were continent while 12 (20%) were either
      incontinent or utilizing clean intermittent catheterization (CIC). Statistical
      analysis revealed that age of untethering, type of cutaneous lesion, level of
      conus, presence of hydronephrosis, and high-grade vesicoureteral reflux (VUR)
      were not independent predictors of continence. In patients with a cutaneous
      lesion who were asymptomatic, 19/20 obtained continence post-TCR (*p = 0.036). In
      patients who were old enough to assess continence pre-TCR, 14/25 patients were
      continent pre-TCR and 11/25 were incontinent. Of the 14 who were continent pre
      TCR, all remained continent post-TCR (*p = 0.002). Of the 11 who were incontinent
      pre-TCR, five (45%) eventually became continent post-TCR. Assessment of
      urodynamic data revealed that neither pre- nor post-TCR urodynamics predicted
      continence status. CONCLUSION: Isolated cutaneous lesions and preoperative
      continence status are positive predictors for post-TCR continence. While pre- and
      post-TCR urodynamics do not predict continence status, their utility in
      preoperative work-up, monitoring for retethering, and long-term urologic follow
      up requires further examination.

PMID- 25067799
TI  - Chronic baroreflex activation effects on sympathetic nerve traffic, baroreflex
      function, and cardiac haemodynamics in heart failure: a proof-of-concept study.
AB  - AIMS: Heart failure (HF) pathophysiology is believed to be mediated by autonomic
      dysfunction, including chronic sympathoexcitation and diminished baroreflex
      sensitivity, which correlate with mortality risk. Baroreflex activation therapy
      (BAT) is a device-based treatment providing chronic baroreflex activation through
      electrical stimulation of the carotid sinus. BAT chronically reduces sympathetic
      activity in resistant hypertension. The purpose of this investigation is to
      determine BAT effects in clinical HF. METHODS AND RESULTS: In a single-centre,
      open-label evaluation, patients with NYHA class III HF, EF <40%, optimized
      medical therapy, and ineligible for cardiac resynchronization received BAT for 6
      months. Efficacy was assessed with serial measurement of muscle sympathetic nerve
      activity (MSNA) and clinical measures of quality of life and functional capacity.
      Eleven patients participated in the trial. MSNA was reduced over 6 months from
      45.1 +/- 7.7 to 31.3 +/- 8.3 bursts/min and from 67.6 +/- 12.7 to 45.1 +/- 11.6
      bursts/100 heartbeats, decreases of 31% and 33%, respectively (P < 0.01).
      Concomitant improvements occurred in baroreflex sensitivity, EF, NYHA class,
      quality of life and 6 min hall walk (6 MHW) distance (P <= 0.05 each). On an
      observational basis, hospitalization and emergency department visits for
      worsening HF were markedly reduced. One complication, perioperative anaemia
      requiring transfusion, occurred during the study. CONCLUSION: BAT was safe and
      provided chronic improvement in MSNA and clinical variables. Based on present
      understanding of HF pathophysiology, these results suggest that BAT may improve
      outcome in HF by modulating autonomic balance. Prospective, randomized trials to
      test the hypothesis are warranted.

PMID- 25067800
TI  - Scudder Oration on Trauma. A century of evolution in trauma resuscitation.

PMID- 25067802
TI  - Tape-guided pure laparoscopic hepatectomy for laterally located tumors: a
      technique to yield an appropriate tumor-free surgical margin and to make
      parenchymal transection easier.

PMID- 25067801
TI  - General and vascular surgery readmissions: a systematic review.

PMID- 25067803
TI  - A model of disruptive surgeon behavior in the perioperative environment.
AB  - BACKGROUND: Surgeons are the physicians with the highest rates of documented
      disruptive behavior. We hypothesized that a unified conceptual model of
      disruptive surgeon behavior could be developed based on specific individual and
      system factors in the perioperative environment. STUDY DESIGN: Semi-structured
      interviews were conducted with 19 operating room staff of diverse occupations at
      a single institution. Interviews were analyzed using grounded theory methods.
      RESULTS: Participants described episodes of disruptive surgeon behavior,
      personality traits of perpetrators, environmental conditions of power, and
      situations when disruptive behavior was demonstrated. Verbal hostility and
      throwing or hitting objects were the most commonly described disruptive
      behaviors. Participants indicated that surgical training attracts and creates
      individuals with particular personality traits, including a sense of shame.
      Interviewees stated this behavior is tolerated because surgeons have unchecked
      power, have strong money-making capabilities for the institution, and tend to
      direct disruptive behavior toward the least powerful employees. The most frequent
      situational stressors were when something went wrong during an operation and
      working with unfamiliar team members. Each factor group (ie, situational
      stressors, cultural conditions, and personality factors) was viewed as being
      necessary, but none of them alone were sufficient to catalyze disruptive behavior
      events. CONCLUSIONS: Disruptive physician behavior has strong implications for
      the work environment and patient safety. This model can be used by hospitals to
      better conceptualize conditions that facilitate disruptive surgeon behavior and
      to establish programs to mitigate conduct that threatens patient safety and
      employee satisfaction.

PMID- 25067804
TI  - A decade analysis of trends and outcomes of bariatric surgery in Medicare
      beneficiaries.
AB  - BACKGROUND: In 2006, the Centers for Medicare and Medicaid Services issued a
      National Coverage Determination (NCD), which mandates that bariatric procedures
      be performed only at accredited centers. The aim of this study was to analyze
      outcomes of Medicare beneficiaries who underwent bariatric surgery before (2001
      through 2005) vs after (2006 through 2010) implementation of the NCD. STUDY
      DESIGN: The Nationwide Inpatient Sample database was used to analyze data on
      patients who underwent bariatric surgery between 2001 and 2010. Main outcomes
      measures were demographics, length of stay, risk-adjusted inpatient morbidity and
      mortality, and cost. RESULTS: There were 775,040 patients who underwent bariatric
      surgery, with 16% of the patients Medicare beneficiaries. There was an overall
      trend for improved in-hospital mortality during the decade (0.35% in 2001 to
      0.10% in 2010). Medicare patients who underwent bariatric surgery had higher
      rates of comorbidities and a higher rate of in-hospital mortality than non
      Medicare patients. After the NCD, there was a significant reduction of the in
      hospital mortality (0.56% vs 0.23%; p < 0.01) and serious morbidity (9.92% vs
      6.98%; p < 0.01) for Medicare patients and a similar reduction of the in-hospital
      mortality (0.18% vs 0.08%; p < 0.01) and serious morbidity (6.84% vs 5.08%; p <
      0.01) for non-Medicare patients. Compared with patients who underwent stapling
      bariatric procedures at accredited centers, patients at nonaccredited centers had
      higher risk-adjusted in-hospital mortality (odds ratio = 3.53; 95% CI, 1.01-6.52)
      and serious morbidity (odds ratio = 1.18; 95% CI, 1.07-1.30). After the NCD, use
      of bariatric surgery within Medicare beneficiaries increased by 71%. CONCLUSIONS:
      Outcomes of bariatric surgery in Medicare beneficiaries have improved
      substantially since the 2006 NCD. Facility accreditation appears to be a
      contributing factor to the observed improvement in outcomes.

PMID- 25067805
TI  - Reinforcement of the intestinal mucus layer protects against Clostridium
      difficile intestinal injury in vitro.
AB  - BACKGROUND: Clostridium difficile infection is increasing in incidence and
      severity. Attributable factors include virulence factors, including C difficile
      toxins A and B, as well as host immunologic status. The mucus component of the
      intestinal barrier is impaired by malnutrition, shock insults, and alterations in
      the gut microbiome. Exogenous phosphatidylcholine (PC) administration results in
      reinforcement of the mucus layer and is of therapeutic benefit in chronic
      ulcerative colitis. We therefore studied the role of exogenous PC combined with
      secretory immunoglobulin A (IgA) in intestinal barrier function against C
      difficile infection in vitro. STUDY DESIGN: Dimeric IgA was placed in the basal
      chambers of mucus-producing (HT29-methotrexate) and non-mucus-producing (HT29)
      strains of intestinal epithelial monolayers and allowed to undergo transcytosis
      and, in additional experiments, exogenous colostral IgA (30 ng/mL) was added to
      the apical media. After subsequent coculture with PC and C difficile toxin A in
      the apical chamber, tumor necrosis factor-alpha, interleukin-6, toxin A uptake,
      intestinal epithelial cell monolayer permeability, and necrosis were determined.
      RESULTS: A significant decrease of 4- to 5-fold in tumor necrosis factor-alpha
      and interleukin-6 levels and equally significant decreases in toxin A uptake and
      permeability changes in the intestinal cell monolayers with mucus or PC and
      transcytosed or colostral IgA vs control are shown. All groups analyzed also
      displayed a 2- to 3-fold reduction in necrosis. CONCLUSIONS: Mucus or "exogenous"
      mucus in the form of PC has a synergistic role with secretory IgA in barrier
      defense against C difficile toxin A. Exogenous PC administration can be a
      therapeutic adjunct in patients with severe or recalcitrant C difficile
      infection.

PMID- 25067806
TI  - Discrepant HIV results resolved by human DNA testing.
AB  - A high-risk patient was informed of a positive HIV antibody/antigen test.
      However, follow-up samples taken 2-3 months later for HIV RNA and anti-HIV
      antibodies were negative. Human DNA testing confirmed that all samples were from
      this patient, excluding a sample mix-up. Laboratory investigations revealed a
      likely splash-over contamination event. 

PMID- 25067807
TI  - Limited diagnostic value of routine screening of neonates with the urinary group
      B streptococcal antigen tests.
AB  - BACKGROUND: A urinary latex test for detection of antigens from group B
      Streptococcus (GBS) has been used for the diagnosis of invasive GBS disease.
      However, the value of routine screening of infants with this test has not been
      determined. METHODS: All infants admitted to Linkou Chang-Gung Memorial Hospital
      (Taoyuan, Taiwan) from January 2005 to May 2013 were screened with a urinary GBS
      antigen test (Wellcogen Strep B). Medical records were retrospectively reviewed
      to determine the diagnostic value of this test. RESULTS: A total of 14,277
      infants were tested and 38 cases had confirmed diagnoses of invasive GBS disease
      (34 bacteremia, 18 meningitis, 14 both), corresponding to a prevalence of 0.27%
      among our admitted infants. A total of 106 infants had positive results, but only
      26 had confirmed disease. Among infants with confirmed disease, 12 had negative
      antigen results. These data allowed calculation of the sensitivity (68.4%),
      specificity (99.4%), positive predictive value (24.5%), and negative predictive
      value (99.9%). Adjusting for prevalence, the disease probability of a positive
      test result was 23.6%, and the probability of a negative post-test result was
      0.09%. The absolute risk reduction of a negative result was very small (0.18%).
      Analysis of demographic, clinical, and laboratory parameters indicated that late
      age of onset (>=7 days-old), presence of seizure, fever, respiratory distress,
      leukopenia, bandemia, thrombocytopenia, coagulopathy, metabolic acidosis, and
      elevated levels of C-reactive protein (CRP) were significantly related to the
      presence of a true positive test result. CONCLUSION: In our study population, the
      positive predictive value of the GBS antigen test was poor and the risk reduction
      of a negative result was weak. These results indicate that routine screening with
      this test has a limited diagnostic value. However, GBS antigen testing appears to
      be useful for early detection of disease in infants with certain demographic,
      clinical, and laboratory risk factors.

PMID- 25067808
TI  - Insights into the asymmetric heterogeneous catalysis in porous organic polymers:
      constructing a TADDOL-embedded chiral catalyst for studying the structure
      activity relationship.
AB  - Construction of porous organic polymers (POPs) as asymmetric catalysts remains as
      an important but challenging task. Herein, we exploit the "bottom-up" strategy to
      facilely synthesize an alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5
      dimethanol (TADDOL)-based chiral porous polymer (TADDOL-CPP) for highly efficient
      asymmetric catalysis. Constructed through the covalent linkages among the three
      dimensional rigid monomers, TADDOL-CPP possesses hierarchical porous structure,
      high Brunauer-Emmett-Teller (BET) surface area, together with abundant and
      uniformly-distributed chiral sites. In the presence of [Ti(OiPr)4], TADDOL-CPP
      acts as a highly efficient and recyclable catalyst in the asymmetric addition of
      diethylzinc (Et2Zn) to aromatic aldehydes. Based on the direct observation of the
      key intermediates, the reaction mechanism has been revealed by solid-state (13)C
      magic-angle spinning (MAS) NMR spectroscopy. In combination with the catalytic
      testing results, characterization on the working catalyst provides further
      information for understanding the structure-activity relationship. We suggest
      that the catalytic activity of TADDOL-CPP is largely affected by the structural
      rigidity, cooperative catalysis, local chiral environment, and hierarchical
      porous framework. We expect that the information obtained herein will benefit to
      the designed synthesis of robust POP catalysts toward practical applications.

PMID- 25067809
TI  - Response to Barranger E, Ihrai T, response to the article by Thill et al.: "The
      Central-European SentiMag study: Sentinel lymph node biopsy with supermagnetic
      iron oxide (SPIO) vs. radioisotope". The Breast 2014, 23(2):175-9.

PMID- 25067810
TI  - Insect-Human Hybrid Eye (IHHE): an adaptive optofluidic lens combining the
      structural characteristics of insect and human eyes.
AB  - Insect compound eyes and human camera eyes are two exquisite optical systems
      created by nature. The compound eye boasts an angle of view (AOV) up to 180
      degrees  thanks to its hemispherical arrangement of hundreds of prime microscale
      lenses. The camera eye, on the other hand, can change shape to focus on objects
      at various depths, yet accepts light within a smaller AOV. Imitations of either
      imaging system have been abundant but with limited success. Here, we describe a
      reconfigurable polymeric optofluidic device that combines the architectural
      merits of both vision mechanisms, featuring a large AOV (up to 120 degrees ) with
      adaptive focusing capabilities (from 0 to 275 diopter (D)). This device consists
      of bi-layered microfluidics: an array of millimeter-sized fluidic lenses is
      integrated into the top layer and arranged on an elastomeric membrane embedded
      within the bottom layer. The membrane can be deformed from a planar surface into
      a series of dome-shaped geometries, rearranging individual fluidic lenses in
      desired curvilinear layouts. Meanwhile, each fluidic lens can vary its radius of
      curvature for a monocular depth sensation. Such a design presents a new
      perspective of tunable optofluidics for a broad range of applications, such as
      robotic vision and medical laparoendoscopy, where adaptive focalization with a
      large viewing angle is a clear advantage. 

PMID- 25067811
TI  - Trends in reoperation for female stress urinary incontinence: A nationwide study.
AB  - AIMS: Using the National Health Insurance (NHI) database in Taiwan, the study
      aimed to evaluate the rates and associated factors for reoperation of female
      stress incontinence. METHODS: Records of female patients who had received a
      primary surgical treatment for stress incontinence from January 2000 to December
      2006 were retrieved. Among these, patients who had reoperations during follow-up
      till December 2010 were identified. The data were analyzed for reoperation rates,
      surgery methods, patient demography, surgeon, and hospital attributes. RESULTS:
      Among 14,613 patients with a mean follow-up of 86.28 +/- 26.76 months, 563
      (3.85%) had reoperations, an incidence rate of 54.37 per 10,000 person year (PY).
      Injection procedures had the highest reoperation rate of 893.30/10,000 PY. The
      adjusted hazard ratio (HR) of reoperation was higher for mid-urethral sling when
      compared to pubovaginal sling (HR 1.54, 95% CI 1.16-2.05) or retropubic
      urethropexy including Burch operation (HR 1.30, 95% CI 1.04-1.61). Surgeons with
      high service volumes tended to have fewer reoperations. No correlations were
      noted between the reoperation rate with patient age, surgeon age/gender, year of
      operation and hospital status. However, urologists had higher reoperation rates
      than gynecologists. For repeat surgery, the majority of patients chose the same
      specialty but different surgical types. Mid-urethral sling was used most commonly
      in 48.85% of reoperations. CONCLUSIONS: Substantial number of patients need
      reoperation for stress incontinence. The choice of primary surgery type and
      surgeon specialty may affect the reoperation rates. Mid-urethral sling is the
      most common reoperation choice.

PMID- 25067813
TI  - Removing artefacts from TMS-EEG recordings using independent component analysis:
      importance for assessing prefrontal and motor cortex network properties.
AB  - INTRODUCTION: The combination of transcranial magnetic stimulation and
      electroencephalography (TMS-EEG) is emerging as a powerful tool for causally
      investigating cortical mechanisms and networks. However, various artefacts
      contaminate TMS-EEG recordings, particularly over regions such as the
      dorsolateral prefrontal cortex (DLPFC). The aim of this study was to substantiate
      removal of artefacts from TMS-EEG recordings following stimulation of the DLPFC
      and motor cortex using independent component analysis (ICA). METHODS: 36 healthy
      volunteers (30.8 +/- 9 years, 9 female) received 75 single TMS pulses to the left
      DLPFC or left motor cortex while EEG was recorded from 57 electrodes. A subset of
      9 volunteers also received 50 sham pulses. The large TMS artefact and early
      muscle activity (-2 to ~15 ms) were removed using interpolation and the remaining
      EEG signal was processed in two separate ICA runs using the FastICA algorithm.
      Five sub-types of TMS-related artefacts were manually identified: remaining
      muscle artefacts, decay artefacts, blink artefacts, auditory-evoked potentials
      and other noise-related artefacts. The cause of proposed blink and auditory
      evoked potentials was assessed by concatenating known artefacts (i.e. voluntary
      blinks or auditory-evoked potentials resulting from sham TMS) to the TMS trials
      before ICA and evaluating grouping of resultant independent components (ICs).
      Finally, we assessed the effect of removing specific artefact types on TMS-evoked
      potentials (TEPs) and TMS-evoked oscillations. RESULTS: Over DLPFC, ICs from
      proposed muscle and decay artefacts correlated with TMS-evoked muscle activity
      size, whereas proposed TMS-evoked blink ICs combined with voluntary blinks and
      auditory ICs with auditory-evoked potentials from sham TMS. Individual artefact
      sub-types characteristically distorted each measure of DLPFC function across the
      scalp. When free of artefact, TEPs and TMS-evoked oscillations could be measured
      following DLPFC stimulation. Importantly, characteristic TEPs following motor
      cortex stimulation (N15, P30, N45, P60, N100) could be recovered from artefactual
      data, corroborating the reliability of ICA-based artefact correction.
      CONCLUSIONS: Various different artefacts contaminate TMS-EEG recordings over the
      DLPFC and motor cortex. However, these artefacts can be removed with apparent
      minimal impact on neural activity using ICA, allowing the study of TMS-evoked
      cortical network properties.

PMID- 25067812
TI  - Neural correlates of language and non-language visuospatial processing in
      adolescents with reading disability.
AB  - Despite anecdotal evidence of relative visuospatial processing strengths in
      individuals with reading disability (RD), only a few studies have assessed the
      presence or the extent of these putative strengths. The current study examined
      the cognitive and neural bases of visuospatial processing abilities in
      adolescents with RD relative to typically developing (TD) peers. Using both
      cognitive tasks and functional magnetic resonance imaging (fMRI) we contrasted
      printed word recognition with non-language visuospatial processing tasks.
      Behaviorally, lower reading skill was related to a visuospatial processing
      advantage (shorter latencies and equivalent accuracy) on a geometric figure
      processing task, similar to findings shown in two published studies. FMRI
      analyses revealed key group by task interactions in patterns of cortical and
      subcortical activation, particularly in frontostriatal networks, and in the
      distributions of right and left hemisphere activation on the two tasks. The
      results are discussed in terms of a possible neural tradeoff in visuospatial
      processing in RD. 

PMID- 25067814
TI  - Neuroimaging paradigms for tonotopic mapping (II): the influence of acquisition
      protocol.
AB  - Numerous studies on the tonotopic organisation of auditory cortex in humans have
      employed a wide range of neuroimaging protocols to assess cortical frequency
      tuning. In the present functional magnetic resonance imaging (fMRI) study, we
      made a systematic comparison between acquisition protocols with variable levels
      of interference from acoustic scanner noise. Using sweep stimuli to evoke
      travelling waves of activation, we measured sound-evoked response signals using
      sparse, clustered, and continuous imaging protocols that were characterised by
      inter-scan intervals of 8.8, 2.2, or 0.0 s, respectively. With regard to
      sensitivity to sound-evoked activation, the sparse and clustered protocols
      performed similarly, and both detected more activation than the continuous
      method. Qualitatively, tonotopic maps in activated areas proved highly similar,
      in the sense that the overall pattern of tonotopic gradients was reproducible
      across all three protocols. However, quantitatively, we observed substantial
      reductions in response amplitudes to moderately low stimulus frequencies that
      coincided with regions of strong energy in the scanner noise spectrum for the
      clustered and continuous protocols compared to the sparse protocol. At the same
      time, extreme frequencies became over-represented for these two protocols, and
      high best frequencies became relatively more abundant. Our results indicate that
      although all three scanning protocols are suitable to determine the layout of
      tonotopic fields, an exact quantitative assessment of the representation of
      various sound frequencies is substantially confounded by the presence of scanner
      noise. In addition, we noticed anomalous signal dynamics in response to our
      travelling wave paradigm that suggest that the assessment of frequency-dependent
      tuning is non-trivially influenced by time-dependent (hemo)dynamics when using
      sweep stimuli.

PMID- 25067815
TI  - Stochastic geometric network models for groups of functional and structural
      connectomes.
AB  - Structural and functional connectomes are emerging as important instruments in
      the study of normal brain function and in the development of new biomarkers for a
      variety of brain disorders. In contrast to single-network studies that presently
      dominate the (non-connectome) network literature, connectome analyses typically
      examine groups of empirical networks and then compare these against standard
      (stochastic) network models. The current practice in connectome studies is to
      employ stochastic network models derived from social science and engineering
      contexts as the basis for the comparison. However, these are not necessarily best
      suited for the analysis of connectomes, which often contain groups of very
      closely related networks, such as occurs with a set of controls or a set of
      patients with a specific disorder. This paper studies important extensions of
      standard stochastic models that make them better adapted for analysis of
      connectomes, and develops new statistical fitting methodologies that account for
      inter-subject variations. The extensions explicitly incorporate geometric
      information about a network based on distances and inter/intra hemispherical
      asymmetries (to supplement ordinary degree-distribution information), and utilize
      a stochastic choice of network density levels (for fixed threshold networks) to
      better capture the variance in average connectivity among subjects. The new
      statistical tools introduced here allow one to compare groups of networks by
      matching both their average characteristics and the variations among them. A
      notable finding is that connectomes have high "smallworldness" beyond that
      arising from geometric and degree considerations alone. 

PMID- 25067816
TI  - Pre-existing brain states predict risky choices.
AB  - Rational decision-making models assume that people resolve an economic problem
      based on its properties and the underlying utility. Here we challenge this view
      by examining whether pre-stimulus endogenous neuronal fluctuations can bias
      economic decisions. We recorded subjects' pre-stimulus neural activation patterns
      with fMRI before presentation and choice between pairs of certain outcomes and
      risky gambles. Our results indicate that activities in the left nucleus accumbens
      and medial frontal gyrus can bias subsequent risky decision making, showing that
      neuronal activities in regions associated with uncertainty and reward processing
      are involved in biasing subsequent choice selection. This finding challenges
      theories which propose that choices merely reveal stable underlying distributions
      of hedonic utility. Endogenous brain states of this sort might originate from a
      systematic cause or a stochastic type of neural noise, which can be construed as
      contextual factors that shape people's decision making. 

PMID- 25067817
TI  - Inhibition of somatosensory-evoked cortical responses by a weak leading stimulus.
AB  - We previously demonstrated that auditory-evoked cortical responses were
      suppressed by a weak leading stimulus in a manner similar to the prepulse
      inhibition (PPI) of startle reflexes. The purpose of the present study was to
      investigate whether a similar phenomenon was present in the somatosensory system,
      and also whether this suppression reflected an inhibitory process. We recorded
      somatosensory-evoked magnetic fields following stimulation of the median nerve
      and evaluated the extent by which they were suppressed by inserting leading
      stimuli at an intensity of 2.5-, 1.5-, 1.1-, or 0.9-fold the sensory threshold
      (ST) in healthy participants (Experiment 1). The results obtained demonstrated
      that activity in the secondary somatosensory cortex in the hemisphere
      contralateral to the stimulated side (cSII) was significantly suppressed by a
      weak leading stimulus with the intensity larger than 1.1-fold ST. This result
      implied that the somatosensory system had an inhibitory process similar to that
      of PPI. We then presented two successive leading stimuli before the test
      stimulus, and compared the extent of suppression between the test stimulus-evoked
      responses and those obtained with the second prepulse alone and with two
      prepulses (first and second) (Experiment 2). When two prepulses were preceded,
      cSII responses to the second prepulse were suppressed by the first prepulse,
      whereas the ability of the second prepulse to suppress the test stimulus remained
      unchanged. These results suggested the presence of at least two individual
      pathways; response-generating and inhibitory pathways. 

PMID- 25067818
TI  - Local awakening: regional reorganizations of brain oscillations after sleep.
AB  - Brain functions express rhythmic fluctuations accompanied by sleep and
      wakefulness each day, but how sleep regulates brain rhythms remains unclear.
      Following the dose-dependent local sleep concept, two succeeding questions
      emerge: (1) is the sleep regulation a network-specific process; and (2) is the
      awakening state dependent on the previous sleep stages? To answer the questions,
      we conducted simultaneous EEG and fMRI recordings over 22 healthy male
      participants, along pre-sleep, nocturnal sleep and awakening. Using paired
      comparisons between awakening and pre-sleep conditions, three scenarios of the
      regional specificity were demonstrated on awakening: (1) the default-mode and
      hippocampal networks maintained similar connectivity and spectral power; (2) the
      sensorimotor network presented reduced connectivity and spectral power; and (3)
      the thalamus demonstrated substantially enhanced connectivity to the neo-cortex
      with decreased spectral power. With regard to the stage effect, the deep sleep
      group had significant changes in both functional connectivity and spectral power
      on awakening, whereas the indices of light sleep group remained relatively
      quiescent after sleep. The phenomena implied that slow-wave sleep could be key to
      rebooting the BOLD fluctuations after sleep. In conclusion, the regional
      specificity and the stage effect were verified in support of the local awakening
      concept, indicating that sleep regulation leads to the reorganization of brain
      networks upon awakening. 

PMID- 25067819
TI  - A longitudinal study of auditory evoked field and language development in young
      children.
AB  - The relationship between language development in early childhood and the
      maturation of brain functions related to the human voice remains unclear. Because
      the development of the auditory system likely correlates with language
      development in young children, we investigated the relationship between the
      auditory evoked field (AEF) and language development using non-invasive child
      customized magnetoencephalography (MEG) in a longitudinal design. Twenty
      typically developing children were recruited (aged 36-75 months old at the first
      measurement). These children were re-investigated 11-25 months after the first
      measurement. The AEF component P1m was examined to investigate the developmental
      changes in each participant's neural brain response to vocal stimuli. In
      addition, we examined the relationships between brain responses and language
      performance. P1m peak amplitude in response to vocal stimuli significantly
      increased in both hemispheres in the second measurement compared to the first
      measurement. However, no differences were observed in P1m latency. Notably, our
      results reveal that children with greater increases in P1m amplitude in the left
      hemisphere performed better on linguistic tests. Thus, our results indicate that
      P1m evoked by vocal stimuli is a neurophysiological marker for language
      development in young children. Additionally, MEG is a technique that can be used
      to investigate the maturation of the auditory cortex based on auditory evoked
      fields in young children. This study is the first to demonstrate a significant
      relationship between the development of the auditory processing system and the
      development of language abilities in young children.

PMID- 25067821
TI  - Serum free light chains of immunoglobulins as biomarkers for systemic sclerosis
      characteristics, activity and severity.
AB  - Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease.
      Humoral immunity and B cells are thought to play an important role in the
      pathophysiology of the disease. B cells are activated, produce specific
      autoantibodies and profibrotic cytokines. One way to assess B cell activation is
      to measure serum free light chains of immunoglobulins (sFLC) levels. We assess
      here sFLC levels in patients with systemic sclerosis (SSc) and their correlation
      with the disease characteristics, activity and severity. One hundred and thirty
      four SSc patients were prospectively enrolled and compared to 401 age- and sex
      matched healthy controls. sFLC levels were measured by a new quantitative
      immunoassay. sFLC levels were significantly higher in SSc patients than in
      healthy controls. sFLC levels correlated with modified Rodnan skin score and were
      independently associated with the presence of interstitial lung disease and its
      severity. In univariate analysis, sFLC levels correlated with SSc activity, as
      measured by the European Scleroderma Study Group activity index, and severity, as
      measured by the Medsger's total severity score. In multivariate analysis, beta2
      microglobulin levels correlated with disease activity, BAFF levels with severity
      and sFLC with neither of these. Other B-cell activation biomarkers (IgG, IgA,
      beta2-microglobulin and BAFF) were independently correlated with sFLC. sFLC
      levels are elevated in SSc and are independently associated with lung disease and
      its severity. B-cell activation biomarkers, including sFLC, beta2-microglobulin
      and BAFF, correlate with disease severity and activity. These results further
      support the role of B cell activation in the pathophysiology of SSc. 

PMID- 25067822
TI  - Enantio-separation of drugs with multiple chiral centers by chromatography and
      capillary electrophoresis.
AB  - Some drugs with more than one chiral center are of high medicinal values.
      However, the chiral resolution of such types of racemate is a challenging task
      for scientists. The evolution of efficient chiral selectors is a hope for the
      future. Some papers have described such types of chiral resolution. The different
      techniques used for the purpose are HPLC, micellar electrokinetic chromatography,
      supercritical fluid chromatography, capillary electrochromatography and capillary
      electrophoresis. Owing to these facts, it was necessary to review the
      enantiomeric resolution of racemic drugs having more than one chiral center. The
      present article describes the chiral resolution of labetalol, formoterol,
      nadolol, indenolol, nebivolol and diltiazem using above cited techniques. In
      addition, attempts have been made to discuss the chiral recognition mechanism and
      future perspectives.

PMID- 25067820
TI  - The functional anatomy of single-digit arithmetic in children with developmental
      dyslexia.
AB  - Some arithmetic procedures, such as addition of small numbers, rely on fact
      retrieval mechanisms supported by left hemisphere perisylvian language areas,
      while others, such as subtraction, rely on procedural-based mechanisms subserved
      by bilateral parietal cortices. Previous work suggests that developmental
      dyslexia, a reading disability, is accompanied by subtle deficits in retrieval
      based arithmetic, possibly because of compromised left hemisphere function. To
      test this prediction, we compared brain activity underlying arithmetic problem
      solving in children with and without dyslexia during addition and subtraction
      operations using a factorial design. The main effect of arithmetic operation
      (addition versus subtraction) for both groups combined revealed activity during
      addition in the left superior temporal gyrus and activity during subtraction in
      the bilateral intraparietal sulcus, the right supramarginal gyrus and the
      anterior cingulate, consistent with prior studies. For the main effect of
      diagnostic group (dyslexics versus controls), we found less activity in dyslexic
      children in the left supramarginal gyrus. Finally, the interaction analysis
      revealed that while the control group showed a strong response in the right
      supramarginal gyrus for subtraction but not for addition, the dyslexic group
      engaged this region for both operations. This provides physiological evidence in
      support of the theory that children with dyslexia, because of disruption to left
      hemisphere language areas, use a less optimal route for retrieval-based
      arithmetic, engaging right hemisphere parietal regions typically used by good
      readers for procedural-based arithmetic. Our results highlight the importance of
      language processing for mathematical processing and illustrate that children with
      dyslexia have impairments that extend beyond reading. 

PMID- 25067823
TI  - Expanding the structure-activity relationship of sulfoxaflor: the synthesis and
      biological activity of N-heterocyclic sulfoximines.
AB  - BACKGROUND: Sulfoxaflor, a new insect control agent developed by Dow
      AgroSciences, exhibits broad-spectrum control of many sap-feeding insect pests,
      including aphids, whiteflies, leafhoppers, planthoppers and lygus bugs. During
      the development of sulfoxaflor, structure-activity relationship (SAR) exploration
      of the sulfoximine functional group revealed that the nature of the sulfoximine
      nitrogen substituent significantly affects insecticidal acitivity. As part of the
      investigation to probe the various electronic, steric and lipophilic parameters
      at this position, a series of N-heterocyclic sulfoximines were synthesized and
      tested for bioactivity against green peach aphid. RESULTS: Using a variety of
      chemistries, the nitrile substituent was replaced with different substituted five
      and six-membered heterocycles. The compounds in the series were then tested for
      insecticidal acitivty against green peach aphid in foliar spray assays. In spite
      of the larger steric demand of these substituents, the resulting N-heterocyclic
      sulfoximine analogs displayed good levels of efficacy. In particular, the N
      thiazolyl sulfoximines exhibited the greatest activity, with LC50 values as low
      as 1 ppm. CONCLUSIONS: The novel series of N-heterocyclic sulfoximines helped to
      advance the current knowledge of the sulfoxaflor SAR, and demonstrated that the
      structural requirement for the sulfoximine nitrogen position was not limited to
      small, electron-deficient moeities, but rather was tolerant of larger
      functionality.

PMID- 25067824
TI  - Adalimumab monotherapy versus combination therapy with immunomodulators in
      patients with Crohn's disease: a systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Combination therapy with infliximab and azathioprine has
      been shown to be superior to either treatment alone in Crohn's disease (CD).
      However, the benefit of combining adalimumab with an immunomodulator remains
      controversial. The aim of this study was to compare the efficacy of adalimumab
      monotherapy with combination therapy for induction and maintenance of response
      and remission in CD using a meta-analysis of the current literature. METHODS: We
      performed a systematic literature search using Medline, Embase, Cochrane and
      several other databases. Prospective randomized controlled trials, retrospective
      cohort and case-controlled studies were included. The primary outcomes included
      induction of response and remission (up to week 12), maintenance of clinical
      response and remission (1 year) and the need for dose escalation. Several
      subgroup and sensitivity analyses were performed. RESULTS: Eighteen out of 2743
      retrieved studies were included. A meta-analysis of 7 studies assessing induction
      of remission (n=1984) showed that ADA monotherapy was inferior to combination
      therapy [OR=0.78 (0.64-0.96), p=0.02]. A meta-analysis of 4 studies revealed that
      combination therapy was not statistically different from ADA for maintenance of
      remission [OR=1.08 (0.79-1.48), p=0.48]. Combination therapy was also not
      different from ADA monotherapy in terms of requirement for dose escalation
      [OR=1.13 (0.69-1.85), p=0.62]. CONCLUSIONS: Combination therapy with ADA and
      immunomodulator was mildly superior to ADA monotherapy for induction of remission
      in CD. The rate of remission at 1 year and the need for dose escalation were
      similar in both groups. These findings should be interpreted with caution in view
      of possible confounders and should be further validated by randomized controlled
      trials.

PMID- 25067825
TI  - The biguanide metformin alters phosphoproteomic profiling in mouse brain.
AB  - Metformin, a potent antihyperglycemic agent is recommended as the first-line oral
      therapy for type 2 diabetes (T2D). Recently, metformin has been reported to be
      beneficial to neurodegenerative disease models. However, the putative mechanisms
      underlying the neuroprotective effects of metformin in disease models are
      unknown. Thus, we applied LC-MS/MS-based pattern analysis and two-dimensional
      electrophoresis (2DE)-based proteomic approach to understand the global
      phosphoproteomic alteration in the brain of metformin-administrated mice.
      Collectively, LC-MS/MS-based pattern analysis reveals that 41 phosphoproteins
      were upregulated and 22 phosphoproteins were downregulated in the brain of
      metformin-administrated mice. In addition, 5 differentially expressed
      phosphoproteins were identified upon metformin administration by 2DE coupled with
      mass spectrometry. The phosphorylation status of metabolic enzymes was decreased
      while that of mitochondrial proteins was increased by metformin. Interestingly,
      phosphorylated alpha-synuclein was significantly decreased by metformin
      administration. Taken together, our results might provide potential pathways to
      understand the pharmacological effect of metformin on neuroprotection. 

PMID- 25067826
TI  - The pattern of coupling dynamics between postural motion, isotonic hand movements
      and physiological tremor.
AB  - This study was designed to examine differences in the coupling dynamics between
      upper limb motion, physiological tremor and whole body postural sway in young
      healthy adults. Acceleration of the hand and fingers, forearm EMG activity and
      postural sway data were recorded. Estimation of the degree of bilateral and limb
      motion-postural sway coupling was determined by cross correlation, coherence and
      Cross-ApEn analyses. The results revealed that, under postural tremor conditions,
      there was no significant coupling between limbs, muscles or sway across all
      metrics of coupling. In contrast, performing a rapid alternating
      flexion/extension movement about the wrist joint (with one or both limbs)
      resulted in stronger coupling between limb motion and postural sway. These
      results support the view that, for physiological tremor responses, the control of
      postural sway is maintained independent to tremor in the upper limb. However,
      increasing the level of movement about a distal segment of one arm (or both)
      leads to increased coupling throughout the body. The basis for this increased
      coupling would appear to be related to the enhanced neural drive to task-specific
      muscles within the upper limb. 

PMID- 25067828
TI  - The expression of calcium/calmodulin-dependent protein kinase II in the dorsal
      horns of rats with type 1 and type 2 diabetes.
AB  - The activation of calcium/calmodulin-dependent protein kinase II (CaMKII) has
      been proposed as a key factor in chronic pain development. This study therefore
      aimed to investigate the expression of CaMKII in the dorsal horn in a rat model
      of early phase diabetes mellitus (DM) types 1 and 2. Sprague-Dawley rats were
      used. DM1 was induced using streptozotocin (STZ) (55mg/kg injected
      intraperitoneally (i.p.)). DM2 was induced using a combination of a high fat diet
      (HFD) and STZ (35mg/kg i.p.). Controls received an i.p. injection of pure citrate
      buffer solution. DM2 animals and their controls also received HFD 2 weeks prior
      to the i.p. injection. Rats were sacrificed 2 weeks and 2 months after diabetes
      induction. The expression of tCaMKII, pCaMKIIalpha and IB4 in the dorsal horns
      was quantified using immunohistochemistry. Increased expression of tCaMKII and
      pCaMKIIalpha was seen in the dorsal horns of DM1 animals 2 weeks and 2 months
      after diabetes induction. In DM2 animals, similar changes in the expression of
      tCaMKII and pCaMKIIalpha were observed after 2 weeks, but not after 2 months. The
      expression of pCaMKIIalpha was most pronounced in laminae I-III. No difference in
      IB4 expression was observed between the groups. These results suggest a potential
      role for CaMKII in diabetic neuropathy development. Inhibition of CaMKII
      signaling pathways should be further explored as a potential treatment target in
      painful diabetic neuropathy. 

PMID- 25067827
TI  - RELN-expressing neuron density in layer I of the superior temporal lobe is
      similar in human brains with autism and in age-matched controls.
AB  - Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of
      subjects with autism. RELN is synthesized and secreted by a subpopulation of
      neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These
      cells are abundant in the marginal zone during cortical development, many die
      after development is complete, but a small population persists into adulthood. In
      adult brains, RELN is secreted by the surviving CR cells, by a subset of
      GABAergic interneurons in layer I, and by pyramidal cells and GABAergic
      interneurons in deeper cortical layers. It is widely believed that decreased RELN
      in layer I of the cerebral cortex of subjects with autism may result from a
      decrease in the density of RELN expressing neurons in layer I; however, this
      hypothesis has not been tested. We examined RELN expression in layer I of the
      adult human cortex and found that 70% of cells express RELN in both control and
      autistic subjects. We quantified the density of neurons in layer I of the
      superior temporal cortex of subjects with autism and age-matched control
      subjects. Our data show that there is no change in the density of neurons in
      layer I of the cortex of subjects with autism, and therefore suggest that reduced
      RELN expression in the cerebral cortex of subjects with autism is not a
      consequence of decreased numbers of RELN-expressing neurons in layer I. Instead
      reduced RELN may result from abnormal RELN processing, or a decrease in the
      number of other RELN-expressing neuronal cell types. 

PMID- 25067829
TI  - Acute total sleep deprivation potentiates cocaine-induced hyperlocomotion in
      mice.
AB  - Sleep deprivation is common place in modern society. Nowadays, people tend to
      self-impose less sleep in order to achieve professional or social goals. In the
      social context, late-night parties are frequently associated with higher
      availability of recreational drugs with abuse potential. Physiologically, all of
      these drugs induce an increase in dopamine release in the mesolimbic dopaminergic
      system, which leads to hyperlocomotion in rodents. Sleep deprivation also seems
      to play an important role in the events related to the neurotransmission of the
      dopaminergic system by potentiating its behavioral effects. In this scenario, the
      aim of the present study was to investigate the effects of total sleep
      deprivation (6h) on the acute cocaine-induced locomotor stimulation in male mice.
      Animals were sleep deprived or maintained in their home cages and subsequently
      treated with an acute i.p. injection of 15mg/kg cocaine or saline and observed in
      the open field. Total sleep deprivation for 6h potentiated the hyperlocomotion
      induced by acute cocaine administration. In addition, the cocaine sleep deprived
      group showed a decreased ratio central/total locomotion compared to the cocaine
      control group, which might be related to an increase in the impulsiveness of
      mice. Our data indicate that acute periods of sleep loss should be considered
      risk factors for cocaine abuse. 

PMID- 25067830
TI  - Synthesis of branched, nano channeled, ultrafine and nano carbon tubes from PET
      wastes using the arc discharge method.
AB  - Upcycling polymer wastes into useful, and valuable carbon based materials, is a
      challenging process. We report a novel catalyst-free and solvent-free technique
      for the formation of nano channeled ultrafine carbon tubes (NCUFCTs) and
      multiwalled carbon nanotubes (MWCNTs) from polyethylene terephthalate (PET)
      wastes, using rotating cathode arc discharge technique. The soot obtain from the
      anode contains ultrafine and nano-sized solid carbon spheres (SCS) with a mean
      diameter of 221 nm and 100 nm, respectively, formed at the lower temperature
      region of the anode where the temperature is approximately 1700 degrees C. The
      carbon spheres are converted into long "Y" type branched and non-branched NCUFCTs
      and MWCNTs at higher temperature regions where the temperature is approximately
      2600 degrees C, with mean diameters of 364 nm and 95 nm, respectively. Soot
      deposited on the cathode is composed of MWCNTs with a mean diameter of 20 nm and
      other nanoparticles. The tubular structures present in the anode are longer, bent
      and often coiled with lesser graphitization compared to the nanotubes in the soot
      on the cathode.

PMID- 25067831
TI  - Dance floor force reduction influences ankle loads in dancers during drop
      landings.
AB  - OBJECTIVES: Dance floor mechanical properties have the potential to influence the
      high frequency of ankle injuries in dancers. However, biomechanical risk factors
      for injury during human movement on hard, low force reduction floors have not
      been established. The aim of this study was to examine the ankle joint mechanics
      of dancers performing drop landings on dance floors with varied levels of force
      reduction. DESIGN: Repeated measures cross sectional study. METHODS: Fourteen
      dancers performed drop landings on five custom built dance floors. Ankle joint
      mechanics were calculated using a three dimensional kinematic model and inverse
      dynamics approach. RESULTS: Ankle joint kinematic (dorsiflexion; range of motion,
      peak angular velocity and acceleration) and kinetic (plantar flexion; peak joint
      moments and power) variables significantly increased with a decrease in floor
      force reduction. Many of the observed changes occurred within a latency of <0.1s
      post-contact with the floor and were associated with increased vertical ground
      reaction forces and decreased floor vertical deformation. CONCLUSIONS: The
      observed mechanical changes are interpreted as an increase in the load
      experienced by the energy absorbing structures that cross the ankle. The short
      latency of the changes represents a high intensity movement at the ankle during a
      period of limited cognitive neuromuscular control. It is suggested that these
      observations may have injury risk implications for dancers that are related to
      joint stabilization. These findings may be of benefit for further investigation
      of dance injury prevention and support the notion that bespoke force reduction
      standards for dance floors are necessary.

PMID- 25067832
TI  - Shinguards effective in preventing lower leg injuries in football: Population
      based trend analyses over 25 years.
AB  - OBJECTIVES: The majority of football injuries are caused by trauma to the lower
      extremities. Shinguards are considered an important measure in preventing lower
      leg impact abrasions, contusions and fractures. Given these benefits, Federation
      Internationale de Football Association introduced the shinguard law in 1990,
      which made wearing shinguards during matches mandatory. This study evaluated the
      effect of the introduction of the shinguard law for amateur players in the
      Netherlands in the 1999/2000-football season on the incidence of lower leg
      injuries. DESIGN: Time trend analyses on injury data covering 25 years of
      continuous registration (1986-2010). METHODS: Data were retrieved from a system
      that records all emergency department treatments in a random, representative
      sample of Dutch hospitals. All injuries sustained in football by patients aged 6
      65 years were included, except for injuries of the Achilles tendon and Weber
      fractures. Time trends were analysed with multiple regression analyses; a model
      was fitted consisting of multiple straight lines, each representing a 5-year
      period. RESULTS: Patients were predominantly males (92%) and treated for
      fractures (48%) or abrasions/contusions (52%) to the lower leg. The incidence of
      lower leg football injuries decreased significantly following the introduction of
      the shinguard law (1996-2000: -20%; 2001-2005: -25%), whereas the incidence of
      all other football injuries did not. This effect was more prominent at
      weekends/match days. No gender differences were found. CONCLUSIONS: The results
      significantly show a preventive effect of the shinguard law underlining the
      relevance of rule changes as a preventive measure and wearing shinguards during
      both matches and training sessions.

PMID- 25067833
TI  - Quality of life (QoL) and help-seeking in postmenopausal women with urinary
      incontinence (UI): A population based study.
AB  - OBJECTIVE: UI is a common condition among women. UI adversely impacts upon QoL
      and participation in everyday activities. The aim of this study was to determine
      the relationship of QoL and help-seeking in postmenopausal women with UI. DESIGN:
      This cross-sectional correlation study took place from March to May 2012; the
      subjects were selected by multi stage sampling method from various zones of Rasht
      City (North of Iran). The data were collected using personal data form,
      Questionnaire for Urinary Incontinence Diagnose (QUID), Incontinence Severity
      Index (ISI) and Incontinence QoL questionnaire (I-QoL), data were analyzed by
      SPSS at the significant level of P<0.05 and then were compared by parametric and
      non-parametric tests. RESULT: Three hundred and thirteen menopause women aged 45
      60 years (mean 52.9) were recruited in the study. Mean QoL score was 46.18 +/-
      19.91. Only 27.3% of subjects seek care for UI. There was no significant
      correlation between the QoL and help-seeking. CONCLUSION: According to the
      findings although QoL was impaired in women with UI, their help-seeking was low.
      Most of them did not consider UI an important problem; health professionals
      should educate patients and aware patients of available treatments.

PMID- 25067834
TI  - Transgenic cry1C or cry2A rice has no adverse impacts on the life-table
      parameters and population dynamics of the brown planthopper, Nilaparvata lugens
      (Hemiptera: Delphacidae).
AB  - BACKGROUND: Transgenic rice producing the insecticidal protein from Bacillus
      thuringiensis Berliner (Bt) is protected from damage by lepidopteran insect
      pests. However, one of the main concerns about Bt rice is the potential impact on
      non-target herbivores. In the present study, the ecological impacts of two Bt
      rice lines, T1C-19 expressing Cry1C protein and T2A-1 expressing Cry2A protein,
      on the non-target herbivore brown planthopper (BPH), Nilaparvata lugens (Stal),
      were evaluated under laboratory and field conditions. The purpose was to verify
      whether these Bt rice lines could affect the performance of BPH at individual and
      population scales. RESULTS: Laboratory results showed that most of the fitness
      parameters (development duration, survival rate, fecundity, fertility, amount of
      honeydew excreted) of BPH were not significantly affected by the two tested Bt
      rice lines, although the development duration of fourth-instar nymphs fed on T1C
      19 was distinctly longer compared with that on T2A-1 and non-Bt rice plants. Five
      life-table parameters did not significantly differ among rice types. Two-year
      field trials also revealed no significant difference in population dynamics of
      BPH among rice types. CONCLUSION: It is inferred that the tested Bt rice lines
      are unlikely to affect the population growth of BPH.

PMID- 25067835
TI  - Translational aspects of central sensitization induced by primary afferent
      activity: what it is and what it is not.

PMID- 25067836
TI  - Back to the future: the need to resolve analgesic efficacy in human
      immunodeficiency virus neuropathy.

PMID- 25067837
TI  - A true theranostic approach to medicine: towards tandem sensor detection and
      removal of endotoxin in blood.
AB  - Sepsis is one of the leading causes of death around the world. The condition
      occurs when a local infection overcomes the host natural defense mechanism and
      suddenly spreads into the circulatory system, triggering a vigorous, self
      injurious inflammatory host response. The pathogenesis of sepsis is relatively
      well known, one of the most potent immuno-activator being bacterial
      lipopolysaccharide (LPS) - also known as 'endotoxin'. Tests exist to detect
      endotoxin in bodily fluids, but are expensive, not necessarily user-friendly and
      require reporter molecules. In addition, the situation for safe and effective
      anti-endotoxin therapy is problematical. At the present time, endotoxin removal
      through cartridge hemoperfusion is one of the better alternatives to combat
      sepsis. The capability to both measure endotoxemia levels and offer an adapted
      response treatment in a timely manner is crucial for better management and
      improved prognosis, but is currently unavailable. In this context, we describe
      herein preliminary research towards the development of an alternative LPS
      biosensor and an innovative LPS neutralization cartridge to be eventually
      combined in an all-integrated configuration for the theranostic, personalized
      treatment of blood endotoxemia/sepsis. LPS detection is performed in a real-time
      and label-free manner in full human blood plasma, using ultra-high frequency
      acoustic wave sensing in combination with ultrathin, oligoethylene glycol-based
      mixed surface chemistry imposed on piezoelectric quartz discs. Biosensing
      platforms are functionalized with polymyxin B (PMB), a cyclic peptide antibiotic
      with high affinity for LPS. Analogous surface modification is used on glass beads
      for the therapeutic cartridge component of the combined strategy. Incubation of
      LPS-spiked whole blood with PMB-bead chemistry resulted in a significant decrease
      in the production of pro-inflammatory TNF-alpha cytokine. LPS neutralization is
      discussed in relation to the perturbation of its supramolecular chemistry in
      solution. 

PMID- 25067838
TI  - Recognition of bacterial lipopolysaccharide using bacteriophage-adhesin-coated
      long-period gratings.
AB  - In this paper we present a new type of highly sensitive label-free sensor based
      on long-period gratings (LPG) coated with T4 bacteriophage (phage) adhesin. The
      adhesin (gp37) binds Escherichia coli B (E. coli B) by recognizing its bacterial
      lipopolysaccharide (LPS). The LPG biofunctionalization methodology is based on
      coating LPG surface with nickel ions capable of gp37 histidine tag reversible
      binding. For the first time recombinant adhesive phage protein has been used as a
      receptor molecule in biosensing scheme. The specificity of LPS binding by adhesin
      has been tested with LPG-based device and confirmed using Western blot, Enzyme
      Linked Immunosorbent Assay (ELISA) and BIACORE methods. The LPG-based sensor can
      measure bacterial contamination in real time and with a high accuracy. We show
      that T4 phage adhesin binds E. coli B LPS in its native or denatured form. The
      binding is highly specific and irreversible. The applied procedure allows for
      obtaining reusable biosensors. 

PMID- 25067839
TI  - Characterisation of heteroplasmic status at codon 143 of the Botrytis cinerea
      cytochrome b gene in a semi-quantitative AS-PCR assay.
AB  - BACKGROUND: An in-depth understanding of quinone outside inhibitor (QoI)
      fungicide-resistant Botrytis cinerea isolates in a vineyard is expected to
      contribute to the development of an optimum disease management programme for the
      control of grape grey mould. RESULTS: The resistance and structure of the
      cytochrome b gene in B. cinerea collected from a Japanese vineyard were
      characterised. The semi-quantitative allele-specific primer-polymerase chain
      reaction (AS-PCR) assay developed in the present study was able to distinguish
      heteroplasmic status from homoplasmic status at codon 143 of the cytochrome b
      gene in QoI-fungicide-resistant B. cinerea from vineyards in Japan. With this
      assay it was demonstrated that the repeated introduction of QoI fungicide
      selection pressure increased the ratio of G143A-mutated cytochrome b genes in B.
      cinerea isolates. CONCLUSION: It is proposed that the semi-quantitative AS-PCR
      assay is a reliable tool for the detection of QoI fungicide resistance and the
      evaluation of homoplasmic/heteroplasmic status at codon 143 of the cytochrome b
      gene in B. cinerea isolates.

PMID- 25067840
TI  - Part D Formulary and Benefit Design as a Risk-Steering Mechanism.

PMID- 25067841
TI  - MEASURING ECONOMIC GROWTH FROM OUTER SPACE.
AB  - GDP growth is often measured poorly for countries and rarely measured at all for
      cities or subnational regions. We propose a readily available proxy: satellite
      data on lights at night. We develop a statistical framework that uses lights
      growth to augment existing income growth measures, under the assumption that
      measurement error in using observed light as an indicator of income is
      uncorrelated with measurement error in national income accounts. For countries
      with good national income accounts data, information on growth of lights is of
      marginal value in estimating the true growth rate of income, while for countries
      with the worst national income accounts, the optimal estimate of true income
      growth is a composite with roughly equal weights. Among poor-data countries, our
      new estimate of average annual growth differs by as much as 3 percentage points
      from official data. Lights data also allow for measurement of income growth in
      sub- and supranational regions. As an application, we examine growth in Sub
      Saharan African regions over the last 17 years. We find that real incomes in non
      coastal areas have grown faster by 1/3 of an annual percentage point than coastal
      areas; non-malarial areas have grown faster than malarial ones by 1/3 to 2/3
      annual percent points; and primate city regions have grown no faster than
      hinterland areas. Such applications point toward a research program in which
      "empirical growth" need no longer be synonymous with "national income accounts."

PMID- 25067842
TI  - COPING WITH ECONOMIC AND ENVIRONMENTAL SHOCKS: INSTITUTIONS AND OUTCOMES: Moving
      to Higher Ground: Migration Response to Natural Disasters in the Early Twentieth
      Century.

PMID- 25067843
TI  - The Home Economics of E-Money: Velocity, Cash Management, and Discount Rates of M
      Pesa Users.

PMID- 25067844
TI  - Learning from Others' HIV Testing: Updating Beliefs and Responding to Risk.

PMID- 25067845
TI  - Targeting Lynch Victims: Social Marginality or Status Transgressions?
AB  - This paper presents the first evidence yielded by a newly-compiled database of
      known lynch victims. Using information from the original census enumerators'
      manuscripts, we identify the individual- and household-level characteristics of
      more than 900 black males lynched in ten southern states between 1882 and 1930.
      First, we use the information gathered for successfully linked cases to present a
      profile of individual-level and household-level characteristics of a large sample
      of lynch victims. Second, we compare these characteristics to a randomly
      generated sample of black men living in the counties where lynchings occurred. We
      use our findings from this comparative analysis to assess the empirical support
      for alternative theoretical perspectives on the selection of individuals as
      victims of southern mob violence. Third, we consider whether the individual-level
      risk factors for being targeted as a lynch victim varied substantially over time
      or across space. Our results demonstrate that victims were generally less
      embedded within the social and economic fabric of their communities than were
      other black men, suggesting that social marginality increased the likelihood of
      being targeted for lynching. These findings were generally consistent across
      decades, and within different socio-demographic contexts.

PMID- 25067846
TI  - Dasymetric Modeling and Uncertainty.
AB  - Dasymetric models increase the spatial resolution of population data by
      incorporating related ancillary data layers. The role of uncertainty in
      dasymetric modeling has not been fully addressed as of yet. Uncertainty is
      usually present because most population data are themselves uncertain, and/or the
      geographic processes that connect population and the ancillary data layers are
      not precisely known. A new dasymetric methodology - the Penalized Maximum Entropy
      Dasymetric Model (P-MEDM) - is presented that enables these sources of
      uncertainty to be represented and modeled. The P-MEDM propagates uncertainty
      through the model and yields fine-resolution population estimates with associated
      measures of uncertainty. This methodology contains a number of other benefits of
      theoretical and practical interest. In dasymetric modeling, researchers often
      struggle with identifying a relationship between population and ancillary data
      layers. The PEDM model simplifies this step by unifying how ancillary data are
      included. The P-MEDM also allows a rich array of data to be included, with
      disparate spatial resolutions, attribute resolutions, and uncertainties. While
      the P-MEDM does not necessarily produce more precise estimates than do existing
      approaches, it does help to unify how data enter the dasymetric model, it
      increases the types of data that may be used, and it allows geographers to
      characterize the quality of their dasymetric estimates. We present an application
      of the P-MEDM that includes household-level survey data combined with higher
      spatial resolution data such as from census tracts, block groups, and land cover
      classifications.

PMID- 25067847
TI  - Influence of the Modifier Type and its Concentration on Electroosmotic Flow of
      the Mobile Phase in Pressurized Planar Electrochromatography.
AB  - The aim of this work was to find a relationship between electroosmotic flow (EOF)
      velocity of the mobile phase in pressurized planar electrochromatography (PPEC)
      and physicochemical properties like zeta potential, dielectric constant, and
      viscosity of the mobile phase as well as its composition. The study included
      different types of organic modifiers (acetonitrile, methanol, ethanol, acetone,
      formamide, N-methylformamide and N,N-dimethylformamide) in the full concentration
      range. In all experiments, chromatographic glass plates HPTLC RP-18 W from Merck
      (Darmstadt) were used as a stationary phase. During the study we found that there
      is no linear correlation between EOF velocity of the mobile phase and single
      variables such as zeta potential or dielectric constant or viscosity. However,
      there is quite strong linear correlation between EOF velocity of the mobile phase
      and variable obtained by multiplying zeta potential of the stationary phase
      mobile phase interface, by dielectric constant of the mobile phase solution and
      dividing by viscosity of the mobile phase. Therefore, it could be concluded that
      the PPEC system fulfilled the Helmholtz-Smoluchowski equation.

PMID- 25067848
TI  - A Huge PVDF Adsorption Difference Between Resveratrol and epsilon-Viniferin
      Allows to Quantitatively Purify Them and to Assess Their Anti-Tyrosinase
      Property.
AB  - Repeated chromatographic analyses of polyphenolic vine stalks extracts allowed us
      to note a huge adsorption difference on polyvinylidene fluoride (PVDF), between
      trans-resveratrol 1 and (+)-trans-epsilon-viniferin 2. We could optimize the
      conditions (solvent, saturation of the process), for this polymer to adsorb very
      selectively 2, with regard to the monomer 1 that remains in solution. Since
      membrane filters made of PVDF are quite often used for HPLC samples filtration,
      this observation prompted us to inform phytochemists studying plant stilbenoid
      contents. Based on this background information, we developed a straightforward
      and inexpensive enrichment process for either 1 and/or 2, from crude Vitis
      vinifera stalks extracts, allowing to get them in a pure form. Having at hand
      large amounts of these two pure compounds, they were tested and compared to a set
      of other relevant molecules for some biological properties: trans-epsilon
      viniferin 2 was shown to be the most powerful tyrosinase inhibitor, among all
      samples tested.

PMID- 25067849
TI  - The Moral Economy of Violence in the US Inner City.
AB  - In an 8-week period, there were 16 shootings with three fatalities, three
      stabbings, and 14 additional "aggravated assaults" in the four square blocks
      surrounding our field site in the Puerto Rican corner of North Philadelphia. In
      the aftermath of the shoot-outs, the drug sellers operating on our block were
      forced to close down their operations by several mothers who repeatedly called
      the police. Drawing on the concept of moral economy (Thompson, Scott, Taussig),
      Mauss's interpretation of gift exchange, and a political economy critique of
      hypercarceralization in the United States, we understand the high levels of US
      inner-city violence as operating within a moral logic framed by economic scarcity
      and hostile state relations. Residents seek security, self-respect, and profit in
      social networks that compel them to participate in solidary exchanges of
      assistive violence dynamized by kinship and gender obligations. A hierarchical,
      extractive drug economy fills the void left by deindustrialization, resulting in
      a dynamic of embodied primitive accumulation at the expense of addicted customers
      and chronically incarcerated just-in-time street sellers at high risk of assault.
      Nevertheless, the mobilization of violence organizing the illegal drug economy
      also follows ethical norms and obligations that are recognized as legitimate by
      many local residents.

PMID- 25067850
TI  - Compensatory Patterns of Support Among Children's Peer Relationships: A Test
      Using School Friends, Nonschool Friends, and Siblings.
AB  - We examined the extent to which isolated and aggressive 6th graders compensate
      for unsatisfying school friendships by deriving support from siblings and
      nonschool friends and whether this support protects such children from poor
      socioemotional outcomes. Results were as follows: (a) When compared with average
      and aggressive children, isolated children perceived their school friendships as
      least supportive and their favorite sibling relationships as most supportive; (b)
      isolated, aggressive, and average children did not differ in their perceptions of
      support from nonschool friends; and (c) high support from a favorite sibling was
      associated with better adjustment among isolated children on select outcomes.
      Despite the somewhat ameliorating role of siblings for isolated children,
      isolated children with high sibling support remained less well adjusted than did
      average children.

PMID- 25067851
TI  - Cellular senescence in usual type uterine leiomyoma.

PMID- 25067852
TI  - A conservative algorithm for parabolic problems in domains with moving
      boundaries.
AB  - We describe a novel conservative algorithm for parabolic problems in domains with
      moving boundaries developed for modeling in cell biology. The spatial
      discretization is accomplished by applying Voronoi decomposition to a fixed
      rectangular grid. In the vicinity of the boundary, the procedure generates
      irregular Voronoi cells that conform to the domain shape and merge seamlessly
      with regular control volumes in the domain interior. Consequently, our algorithm
      is free of the CFL stability issue due to moving interfaces and does not involve
      cell-merging or mass redistribution. Local mass conservation is ensured by finite
      volume discretization and natural-neighbor interpolation. Numerical experiments
      with two-dimensional geometries demonstrate exact mass conservation and indicate
      an order of convergence in space between one and two. The use of standard meshing
      techniques makes extension of the method to three dimensions conceptually
      straightforward.

PMID- 25067853
TI  - Long Term and Spillover Effects of Health Shocks on Employment and Income.
AB  - We use matching combined with difference-in-differences to identify the causal
      effects of sudden illness, represented by acute hospitalizations, on employment
      and income up to six years after the health shock using linked Dutch hospital and
      tax register data. An acute hospital admission lowers the employment probability
      by seven percentage points and results in a five percent loss of personal income
      two years after the shock. There is no subsequent recovery in either employment
      or income. There are large spillover effects: household income falls by 50
      percent more than the income of the disabled person.

PMID- 25067854
TI  - Seasonal characteristics of flood regimes across the Alpine-Carpathian range.
AB  - The aim of this paper is to analyse the differences in the long-term regimes of
      extreme precipitation and floods across the Alpine-Carpathian range using
      seasonality indices and atmospheric circulation patterns to understand the main
      flood-producing processes. This is supported by cluster analyses to identify
      areas of similar flood processes, both in terms of precipitation forcing and
      catchment processes. The results allow to isolate regions of similar flood
      generation processes including southerly versus westerly circulation patterns,
      effects of soil moisture seasonality due to evaporation and effects of soil
      moisture seasonality due to snow melt. In many regions of the Alpine-Carpathian
      range, there is a distinct shift in flood generating processes with flood
      magnitude as evidenced by a shift from summer to autumn floods. It is argued that
      the synoptic approach proposed here is valuable in both flood analysis and flood
      estimation.

PMID- 25067855
TI  - Cyclical Cohabitation Among Unmarried Parents in Fragile Families.
AB  - Building on past research suggesting that cohabitation is an ambiguous family
      form, the authors examined an understudied residential pattern among unmarried
      parents: cyclical cohabitation, in which parents have multiple cohabitation
      spells with each other. Using 9 years of panel data from the Fragile Families and
      Child Wellbeing Study (N = 2,084), they found that 10% of all parents with
      nonmarital births, and nearly a quarter of those living together when the child
      is 9 years old, are cyclical cohabitors. Cyclically cohabiting mothers reported
      more material hardships than mothers in most other relationship patterns but also
      reported more father involvement with children. On all measures of child well
      being, except grade retention, children of cyclically cohabiting parents fared no
      worse than children of stably cohabiting biological parents and did not differ
      significantly from any other group.

PMID- 25067856
TI  - Conformational Evolution of Elongated Polymer Solutions Tailors the Polarization
      of Light-Emission from Organic Nanofibers.
AB  - Polymer fibers are currently exploited in tremendously important technologies.
      Their innovative properties are mainly determined by the behavior of the polymer
      macromolecules under the elongation induced by external mechanical or
      electrostatic forces, characterizing the fiber drawing process. Although enhanced
      physical properties were observed in polymer fibers produced under strong
      stretching conditions, studies of the process-induced nanoscale organization of
      the polymer molecules are not available, and most of fiber properties are still
      obtained on an empirical basis. Here we reveal the orientational properties of
      semiflexible polymers in electrospun nanofibers, which allow the polarization
      properties of active fibers to be finely controlled. Modeling and simulations of
      the conformational evolution of the polymer chains during electrostatic
      elongation of semidilute solutions demonstrate that the molecules stretch almost
      fully within less than 1 mm from jet start, increasing polymer axial orientation
      at the jet center. The nanoscale mapping of the local dichroism of individual
      fibers by polarized near-field optical microscopy unveils for the first time the
      presence of an internal spatial variation of the molecular order, namely the
      presence of a core with axially aligned molecules and a sheath with almost
      radially oriented molecules. These results allow important and specific fiber
      properties to be manipulated and tailored, as here demonstrated for the
      polarization of emitted light.

PMID- 25067857
TI  - Enrollment in Medicare Advantage plans in Miami-Dade County: evidence of status
      quo bias?
AB  - Evidence from behavioral economics reveals that decision-making in health care
      settings can be affected by circumstances and choice architecture. This paper
      conducts an analysis of choice of private Medicare plans (Medicare Advantage
      plans) in Miami-Dade County. We provide a detailed description of the choice of
      MA plans available in Miami over much of the program's history. Our analysis
      suggests that first becoming eligible for Medicare is the key transition point
      for MA, and that there is significant status quo bias in the MA market. Policy
      that regulates the MA market should anticipate, monitor and account for this
      consumer behavior. 

PMID- 25067858
TI  - Posterior consistency in conditional distribution estimation.
AB  - A wide variety of priors have been proposed for nonparametric Bayesian estimation
      of conditional distributions, and there is a clear need for theorems providing
      conditions on the prior for large support, as well as posterior consistency.
      Estimation of an uncountable collection of conditional distributions across
      different regions of the predictor space is a challenging problem, which differs
      in some important ways from density and mean regression estimation problems.
      Defining various topologies on the space of conditional distributions, we provide
      sufficient conditions for posterior consistency focusing on a broad class of
      priors formulated as predictor-dependent mixtures of Gaussian kernels. This
      theory is illustrated by showing that the conditions are satisfied for a class of
      generalized stick-breaking process mixtures in which the stick-breaking lengths
      are monotone, differentiable functions of a continuous stochastic process. We
      also provide a set of sufficient conditions for the case where stick-breaking
      lengths are predictor independent, such as those arising from a fixed Dirichlet
      process prior.

PMID- 25067859
TI  - Simple Correctors for Elimination of High-Order Modes in Corrugated Waveguide
      Transmission Lines.
AB  - When using overmoded corrugated waveguide transmission lines for high power
      applications, it is necessary to control the mode content of the system. Ideally,
      overmoded corrugated transmission lines operate in the fundamental HE11 mode and
      provide low losses for long distances. Unwanted higher order modes (HOMs),
      particularly LP11 and HE12, are often excited in the experimental systems due to
      practical misalignments in the transmission line system. This paper discusses how
      the unwanted modes propagate along with the fundamental mode in the transmission
      line system by formulating an equation that relates the center of power offset
      and angle of propagation of a beam (for the HE11 and LP11 modes) or the waist
      size and phase front radius of curvature of a beam (for the HE11 and HE12 modes).
      By introducing two miter bend correctors into the transmission system-miter bends
      that have slightly angled or ellipsoidal mirrors-the HOMs can be precisely
      manipulated in the system. This technique can be used to eliminate small
      quantities of unwanted modes, thereby creating a nearly pure fundamental mode
      beam with minimal losses. Examples of these applications are calculated and show
      the theoretical conversion of up to 10% HOM content into the fundamental HE11
      mode with minimal losses.

PMID- 25067860
TI  - Effects of Welfare Reform on Illicit Drug Use Of Adult Women.
AB  - Exploiting changes in welfare policy across states and over time and comparing
      relevant population subgroups within an econometric difference-in-differences
      framework, we estimate the effects of welfare reform on adult women's illicit
      drug use from 1992 to 2002, the period during which welfare reform unfolded in
      the U.S. The analyses are based on all available and appropriate national
      datasets, each offering unique strengths and measuring a different drug-related
      outcome. We investigate self-reported illicit drug use (from the National
      Household Surveys on Drug Abuse and National Surveys on Drug Use and Health),
      drug-related prison admissions (from the National Corrections Reporting Program),
      drug-related arrests (from Federal Bureau of Investigation Uniform Crime
      Reports), and drug-related emergency department episodes (from the Drug Abuse
      Warning Network). We find robust evidence that welfare reform led to a 10-21%
      decline in illicit drug use among women at risk of relying on welfare, as well as
      associated declines in drug-related arrests (6-7%), drug-related hospital
      emergency department episodes (7-11%), and possibly drug-related prison
      admissions (11-19%). The findings indicate that an appropriately designed system
      with sufficient job opportunities for those are able to work can result in both
      increases in employment and decreases in drug use.

PMID- 25067861
TI  - Tautomeric and Microscopic Protonation Equilibria of Anthranilic Acid and Its
      Derivatives.
AB  - The acid-base chemistry of three zwitterionic compounds, namely anthranilic (2
      aminobenzoic acid), N-methylanthranilic and N-phenylanthranilic acid has been
      characterized in terms of the macroconstants Ka1, Ka2, the isoelectric point pHI,
      the tautomerization constant Kz and microconstants k11, k12, k21, k22. The
      potentiometric titration method was used to determine the macrodissociation
      constants. Due to the very poor water solubility of N-phenylanthranilic acid the
      dissociation constants pKa1 and pKa2 were determined in MDM-water mixtures [MDM
      is a co-solvent mixture, consisting of equal volumes of methanol (MeOH), dioxane
      and acetonitrile (MeCN)]. The Yasuda-Shedlovsky extrapolation procedure has been
      used to obtain the values of pKa1 and pKa2 in aqueous solutions. The pKa1 and
      pKa2 values obtained by this method are 2.86 +/- 0.01 and 4.69 +/- 0.03,
      respectively. The tautomerization constant Kz describing the equilibrium between
      unionized form ? zwitterionic form was evaluated by the Kz method based on UV-VIS
      spectrometry. The method uses spectral differences between the zwitterionic form
      (found at isoelectric pH in aqueous solution) and the unionized form (formed in
      an organic solvent of low dielectric constant). The highest value of the Kz
      constant has been observed in the case of N-methylantranilic acid (log10Kz = 1.31
      +/- 0.04). The values of log10Kz for anthranilic and N-phenylanthranilic acids
      are similar and have values of 0.93 +/- 0.03 and 0.90 +/- 0.05, respectively. The
      results indicate that the tested compounds, in aqueous solution around the
      isoelectric point pHI, occur mainly in the zwitterionic form. Moreover, the
      influence of the type of substituent and pH of the aqueous phase on the
      equilibrium were analyzed with regard to the formation and the coexistence of
      different forms of the acids in the examined systems.

PMID- 25067862
TI  - Family Instability and Pathways to Adulthood in Urban South Africa.
AB  - Social, political, epidemiological, and economic forces have produced family
      instability during childhood for many young people transitioning to adulthood in
      South Africa. This study identifies pathways to adulthood for youth in Cape Town
      that capture the timing and sequencing of role transitions across the life
      domains of school, work, and family formation. It then uses these pathways to
      investigate the relationship between childhood family instability and the way
      young people's lives unfold during the transition to adulthood. Results indicate
      that changes in co-residence with parents are associated with following less
      advantageous pathways into adulthood, independent of particular family structure
      or orphan status. Overall, the findings suggest that family instability
      influences not only single transitions for youth, but also combinations of
      transitions. They also indicate the value of a multi-dimensional
      conceptualization of the transition to adulthood in empirical work.

PMID- 25067863
TI  - Geographic Divergence in Mortality in the United States.

PMID- 25067864
TI  - 'Keeping going': chronic joint pain in older people who describe their health as
      good.
AB  - It is common for people with chronic conditions to report their health as good,
      although models of healthy ageing do not account for this. The concept of
      successful ageing focuses on overcoming problems, in contrast to the concept of
      resilience, which can acknowledge vulnerability. Osteoarthritis (OA) is the main
      cause of joint pain in older people, but research in this area has tended to
      focus on OA as an illness. Consequently, our research aimed to explore OA from
      the perspective of wellness. We undertook a longitudinal qualitative study to
      explore 'wellness and resilience' in a group of older people who reported chronic
      joint pain and considered themselves healthy. We interviewed 27 people and
      followed them up with monthly diary sheets, responding to reports of changes
      using their chosen contact method. This article focuses on how resilience relates
      to how people consider themselves to be well. Participants' experience of the
      adversity of their pain varied, and was influenced by context and meaning.
      Participants described 'keeping going' in body, mind and everyday life.
      Flexibility and pragmatism were key aspects of keeping going. The findings
      support a broader version of resilience that incorporates vulnerabilities. In the
      context of health care we suggest that treating the frail body should not come at
      the expense of undermining an older person's sense of a resilient self.

PMID- 25067865
TI  - Feeling in control: comparing older people's experiences in different care
      settings.
AB  - The promotion of choice and control for older people is a policy priority for
      social care services in the United Kingdom and is at the heart of recent drives
      to personalise services. Increasingly, we are seeing a move away from
      institutionalised care (e.g. in care homes) towards enablement, with more
      services being delivered in community-based settings. Extra care housing has been
      promoted as a purpose-built, community-based alternative to residential care for
      older people. However, whilst accounts of users' experiences in particular
      service types are plentiful, the use of different instrumentation and measures
      makes comparison between settings difficult. We combined data from four studies
      where participants were older people either living in care homes or extra care
      housing or receiving care at home. All of these studies asked participants to
      rate their control over daily life, using the Adult Social Care Outcomes Toolkit
      (ASCOT). This paper presents the results of an ordinal logistic regression
      analysis indicating that, after controlling for differences in age, ability to
      perform activities of daily living and self-rated health, setting had a
      significant effect on older people's sense of control. Residents in care homes
      and extra care housing report similar levels of control over daily life but
      consistently report feeling more in control than older people receiving care at
      home. Implications for policy and practice are discussed.

PMID- 25067866
TI  - Emotional Reactivity and Regulation in Head Start Children: Links to Ecologically
      Valid Behaviors and Internalizing Problems.
AB  - Children's emotional reactivity may interact with their regulatory behaviors to
      contribute to internalizing problems and social functioning even early in
      development. Ninety-one preschool children participated in a longitudinal project
      examining children's reactivity and regulatory behaviors as predictors of
      internalizing problems and positive and negative social behavior in the
      classroom. Children who paired negative emotion expression with disengagement
      during a laboratory task showed higher levels of internalizing problems and more
      negative social behavior in the classroom six months later. Positive emotion
      expression paired with engagement during a laboratory task predicted more
      positive social behavior in the classroom six months later. Physiological
      reactivity and regulation also predicted children's social behavior in the
      classroom. Findings suggest that preschool children with maladaptive reactivity
      and regulatory patterns may be at greater risk for internalizing problems even in
      early childhood.

PMID- 25067867
TI  - Genetic vulnerability interacts with parenting and early care education to
      predict increasing externalizing behavior.
AB  - The current study examined interactions among genetic influences and children's
      early environments on the development of externalizing behaviors from 18 months
      to 6 years of age. Participants included 233 families linked through adoption
      (birth parents and adoptive families). Genetic influences were assessed by birth
      parent temperamental regulation. Early environments included both family
      (overreactive parenting) and out-of-home factors (center-based Early Care and
      Education; ECE). Overreactive parenting predicted more child externalizing
      behaviors. Attending center-based ECE was associated with increasing
      externalizing behaviors only for children with genetic liability for
      dysregulation. Additionally, children who were at risk for externalizing
      behaviors due to both genetic variability and exposure to center-based ECE were
      more sensitive to the effects of overreactive parenting on externalizing behavior
      than other children.

PMID- 25067868
TI  - Repercussion of mesophyll-specific overexpression of a soybean cytosolic
      glutamine synthetase gene in alfalfa (Medicago sativa L.) and tobacco (Nicotiana
      tabaccum L.).
AB  - Glutamine synthetase (GS) plays a central role in plant nitrogen metabolism.
      Plant GS occurs as a number of isoenzymes present in either the cytosol (GS1) or
      chloroplast/plastid (GS2). There are several reports of improved performance in
      transgenic plants overexpressing GS1 transgenes driven by the constitutive
      CaMV35S promoter. Improvement has been attributed to the GS1 transgene product
      functioning to enhance re-assimilation of NH4+ released by photorespiration or
      protein degradation. In this paper, alfalfa and tobacco transformants expressing
      a soybean gene driven by a photosynthetic cell-specific promoter have been
      compared to transformants with the same transgene driven by the stronger CaMV35S
      promoter. The two classes of alfalfa and tobacco transformants showed differences
      in the level of GS1 transcript and GS1 protein accumulation, but the difference
      in the total GS activity was small. The discrepancy in the transgene expression
      level and GS activity has been attributed to posttranslational regulation at the
      level of holoprotein stability. Both classes of transformants exhibited similar
      level of improvement in soluble protein and in the rates of photosynthesis and
      photorespiration. The data supports the hypothesis that GS1 made in the mesophyll
      cells is involved in the re-assimilation of NH4+ released via photorespiration
      and/or protein degradation.

PMID- 25067869
TI  - The Effects of Parental Loss on the Psychosocial Wellbeing of AIDS-Orphaned
      Children Living in AIDS-Impacted Communities: Does Gender Matter?

PMID- 25067870
TI  - Automated analysis of the Cinderella story.
AB  - BACKGROUND: AphasiaBank is a collaborative project whose goal is to develop an
      archival database of the discourse of individuals with aphasia. Along with
      databases on first language acquisition, classroom discourse, second language
      acquisition, and other topics, it forms a component of the general TalkBank
      database. It uses tools from the wider system that are further adapted to the
      particular goal of studying language use in aphasia. AIMS: The goal of this paper
      is to illustrate how TalkBank analytic tools can be applied to AphasiaBank data.
      METHODS & PROCEDURES: Both aphasic (n = 24) and non-aphasic (n = 25) participants
      completed a 1-hour standardised videotaped data elicitation protocol. These
      sessions were transcribed and tagged automatically for part of speech. One
      component of the larger protocol was the telling of the Cinderella story. For
      these narratives we compared lexical diversity across the groups and computed the
      top 10 nouns and verbs across both groups. We then examined the profiles for two
      participants in greater detail. CONCLUSIONS: Using these tools we showed that, in
      a story-retelling task, aphasic speakers had a marked reduction in lexical
      diversity and a greater use of light verbs. For example, aphasic speakers often
      substituted "girl" for "stepsister" and "go" for "disappear". These findings
      illustrate how it is possible to use TalkBank tools to analyse AphasiaBank data.

PMID- 25067871
TI  - As We Said, Loneliness (Not Living Alone) Explains Individual Differences in
      Sleep Quality: Reply.

PMID- 25067872
TI  - Outside-In Hemofiltration for Prolonged Operation without Clogging.
AB  - Hemofiltration (HF) is used extensively for continuous renal replacement therapy,
      but long-term treatment is limited by thrombosis leading to fiber clogging.
      Maximum filter life is typically less than 20 hours. We have achieved for the
      first time continuous and consistent hemofiltration for more than 100 hours using
      outside-in hemofiltration with the blood flow into the inter-fiber space (IFS).
      Although thrombi do deposit in the IFS, they have minimal affect on the blood
      flow and filtrate flux due to the three-dimensional system of interconnected
      hydrodynamic flow channels in the IFS. Microscopic examination of sections of the
      fiber bundle showed that deposited thrombi have dimensions about the size of the
      gaps between the hollow fibers and remain isolated from each other. A simple
      mathematical model is developed to describe the effect of thrombus deposition on
      the fluid flow that accounts for the enhanced performance arising from the
      interconnected flow. The hydrodynamic advantage of outside-in HF decreases at low
      anticoagulant concentration due to the instability in the blood and the very high
      volume fraction of thrombi that deposit in the entrance zone of the filter. These
      results clearly demonstrate the significant potential advantages of using outside
      in hemofiltration for long-term renal replacement therapy.

PMID- 25067873
TI  - Pathologic reappraisal of wallenberg syndrome: a pathologic distribution study
      and analysis of literature.
AB  - BACKGROUND: Wallenberg syndrome was first reported by Adolf Wallenberg as arising
      due to the obstruction of the posterior inferior cerebellar artery (PICA), which
      caused an infarct in the lateral medulla oblongata (MO). METHOD: This study was
      carried out on brain tissue from 2 patients with typical Wallenberg syndrome and
      10 autopsy cases without central nervous system disturbances. RESULTS: Patient 1
      exhibited the 3 major neurological symptoms of right crossed sensory disturbance,
      right cerebellar ataxia and bulbar palsy. There was the pathological obstruction
      of the right vertebral artery (VA). Regarding the histopathlogical distribution,
      the infarct extended on the right side to the lateral spinothalamic tract,
      nucleus of the spinal tract of the trigeminal nerve, spinal tract of the
      trigeminal nerve, inferior cerebellar peduncle, spinocerebellar tract and nucleus
      ambiguous. Moreover, a clear infarct in the left lateral MO was pathologically
      identified, but pathological obstruction of the left PICA or left VA could not be
      found. The left cerebellar ataxia and bulbar palsy were observed among these 3
      major symptoms. Patient 2 showed the 3 major symptoms of right crossed sensory
      disturbance, right cerebellar ataxia and bulbar palsy. A pathological luminal
      occlusion was identified in the right PICA. Regarding the histopathological
      lesion, the infarct disturbed on the right side the lateral spinothalamic tract,
      nucleus of the spinal tract of the trigeminal nerve, spinal tract of the
      trigeminal nerve, spinocerebellar tract, inferior cerebellar peduncle and nucleus
      ambiguus. CONCLUSION: Based on our investigation of pathological lesions using
      our 2 autopsies, we suggest calling the cases that satisfy the following 3
      criteria "definite pathologic Wallenberg syndrome": i) identifiable pathological
      obstruction of the PICA or VA; ii) infarction in the lateral MO based on PICA or
      VA obstruction; and iii) a 1-to-1 correspondence between clinical symptoms and
      neuropathological lesions.

PMID- 25067874
TI  - Changes resulting from reflection dialogues on nursing practice.
AB  - BACKGROUND: Reflection is defined here as a process by which, through self
      conversation, one's self and one's behavior acquire meaning. However, people have
      limitations in terms of what they can express and be aware of during reflection.
      This finding points to the importance of facilitators. The purpose of this study
      was to determine what changes can be brought about through reflection dialogues
      on nursing practice. METHODS: The Participants were 9 nurses who worked at three
      institutions in City A, each with about 200 beds. Workplace topics were examined
      through self-reflections and reflection dialogues. The depth of reflection was
      assessed using the three levels of reflection described by Mezirow-{reflecting on
      the content}, {reflecting on the process} and {reflecting on the assumptions}.
      RESULTS: In reflecting on nursing practice, the participants were also divided
      into those who had already reached the highest level, {reflecting on
      assumptions}, via self-reflection, and those who remained at the level of
      {reflecting on processes}, despite the use of reflection dialogues. CONCLUSION:
      The development of reflective thinking on nursing practice was connected not only
      to the participants' desire to explore ways of accepting their individual
      experiences, but may also be connected to whether or not they are able to
      question themselves about their thoughts and preconceptions about nursing work.

PMID- 25067875
TI  - Cerebellar expression of copper chaperone for superoxide, cytosolic cu/zn
      superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock protein 32 in
      patients with menkes kinky hair disease: immunohistochemical study.
AB  - BACKGROUND: To clarify the pathogenesis of cerebellar Purkinje cell death in
      patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we
      investigated the morphological and functional abnormalities of residual Purkinje
      cells in MD patients and the mechanism of cell death. METHODS: Seven MD patients
      and 39 neurologically normal autopsy cases were studied. We performed
      histopathological and quantitative analyses of the Purkinje cells. In addition,
      we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Zn
      superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)],
      oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock
      protein 32 (hsp 32). RESULTS: The surviving MD Purkinje cells showed abnormal
      development, such as somatic sprouts and heterotopic location. Due to
      maldevelopment and degeneration, dendrites showed the cactus and weeping willow
      patterns. Axonal degeneration led to the formation of torpedoes. Quantitative
      analysis revealed loss of approximately 50% of the Purkinje cells in MD patients.
      Almost all of the normal Purkinje cells were positive for immunostaining by anti
      CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and
      axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or
      hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but
      the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of
      the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32,
      respectively. CONCLUSION: In MD patients, about 50% of the Purkinje cells have
      been lost due to maldevelopment and degeneration. In the residual Purkinje cells,
      CCS expression seems to be nearly normal as a protective response to decreased
      SOD1 activity due to copper deficiency. Because oxidative stress is elevated
      secondary to decreased SOD1 activity, hsp 32 is induced as another protective
      mechanism.

PMID- 25067876
TI  - Expansion of genetic testing in the division of functional genomics, research
      center for bioscience and technology, tottori university from 2000 to 2013.
AB  - BACKGROUND: At the Division of Functional Genomics, Research Center for
      Bioscience and Technology, Tottori University, we have been making an effort to
      establish a genetic testing facility that can provide the same screening
      procedures conducted worldwide. METHODS: Direct Sequencing of PCR products is the
      main method to detect point mutations, small deletions and insertions. Multiplex
      Ligation-dependent Probe Amplification (MLPA) was used to detect large deletions
      or insertions. Expansion of the repeat was analyzed for triplet repeat diseases.
      Original primers were constructed for 41 diseases when the reported primers
      failed to amplify the gene. Prediction of functional effects of human nsSNPs
      (PolyPhen) was used for evaluation of novel mutations. RESULTS: From January 2000
      to September 2013, a total of 1,006 DNA samples were subjected to genetic testing
      in the Division of Functional Genomics, Research Center for Bioscience and
      Technology, Tottori University. The hospitals that requested genetic testing were
      located in 43 prefectures in Japan and in 11 foreign countries. The genetic
      testing covered 62 diseases, and mutations were detected in 287 out of 1,006 with
      an average mutation detection rate of 24.7%. There were 77 samples for prenatal
      diagnosis. The number of samples has rapidly increased since 2010. CONCLUSION: In
      2013, the next-generation sequencers were introduced in our facility and are
      expected to provide more comprehensive genetic testing in the near future.
      Nowadays, genetic testing is a popular and powerful tool for diagnosis of many
      genetic diseases. Our genetic testing should be further expanded in the future.

PMID- 25067877
TI  - Bone mineral density in residents of care facilities for the aged and effect of
      pharmacotherapy.
AB  - BACKGROUND: Bone mineral densitometry has been proven to be a powerful tool for
      the diagnosis and treatment of osteoporosis, which is increasing with aging of
      the population, but opportunities to perform bone mineral densitometry in elderly
      facility residents, who are at a high risk of fracture, are scarce. METHODS: We
      measured the bone mineral density in 315 residents of 5 care facilities for the
      aged in middle Tottori Prefecture from 2002 to 2006. We also evaluated residents
      of an elderly nursing home with a history of fragility fracture and those with
      osteoporosis who were administered risedronate for its therapeutic effect.
      RESULTS: The bone mineral density was less than 70% of the young adult mean in
      161 (51.1%) of the 315 subjects (aged 83.1 +/- 7.8 years), 149 (57.8%) of the 258
      women (83.9 +/- 7.2 years), and 12 (21.1%) of the 57 men (79.8 +/- 9.3 years). In
      the 13 subjects who were administered risedronate, the bone mineral density
      increased from 65.8 to 67.2% of the young adult mean from before to after the
      beginning of administration, but it decreased in the control group (n = 9). In
      those administered risedronate, the urinary level of N-telopeptide (a marker for
      bone resorption) began to decrease 3 months after the beginning of the
      administration and showed a significant decrease after 11 months (n = 8) compared
      with the control group. The mean pain score based on the visual analogue scale
      showed significant reduction in the risedronate group compared with the control
      group. CONCLUSION: The bone mineral density was low in the facility residents and
      was less than 70% of the young adult mean in 57.8% of women and in 21.1% of men,
      more frequently than expected. Bone resorption and osteoporotic pain were
      suppressed by risedronate in osteopenic patients in such care facility.

PMID- 25067878
TI  - The Efficacy of Target Biopsy of Suspected Cancer Lesions Detected by Magnetic
      Resonance Imaging and/or Transrectal Ultrasonography during Initial Prostate
      Biopsies: Comparison of Outcomes between Two Physicians.
AB  - BACKGROUND: The efficacy of adding target prostate biopsy (PBx) of suspected
      cancer lesions identified on magnetic resonance imaging (MRI) and/or transrectal
      ultrasonography (TRUS) to initial systematic PBx was evaluated. Moreover, the
      outcomes were compared between 2 physicians. METHODS: We retrospectively
      investigated 238 patients who underwent first-time PBx in our hospital. All
      patients were examined with prostate MRI before PBx. Fourteen systematic biopsies
      were obtained in all patients. When a suspected lesion was present on MRI and/or
      TRUS, the lesion was the target of target PBx. RESULTS: The overall detection
      rate of prostate cancer (PCa) was 45% (106/238). With target PBx, the PCa
      detection rate was 32% overall, while that of suspected lesions seen only on MRI
      was 32%, that of suspected lesions seen only on TRUS was 8% and that of suspected
      lesions seen on both MRI and TRUS was 52%. The same tendency was shown for each
      physician. Comparing systematic PBx and target PBx, the overall rate of Gleason
      score (GS) upgrading with target PBx was 13%. The rate of PCa detected only by
      systematic PBx was 95%. There was no significant difference between the 2
      physicians. CONCLUSION: In initial PBx, the addition of target PBx of suspected
      cancer lesions detected by MRI and/or TRUS to systematic PBx might not be useful
      to improve the cancer detection rate. However, it may enable more accurate risk
      classification and detection of minute cancers with a high GS.

PMID- 25067879
TI  - Epidermal cyst with ossification: a patient report.
AB  - Epidermal cysts are common skin tumors that are composed of a cyst wall of
      epidermal cells and central keratin material. They rarely show ossification. A 68
      year-old man was referred to our clinic for evaluation of multiple cysts on his
      left forehead, left cheek and right shoulder. Histopathological examination
      revealed that all of the cysts were epidermal cysts, and focal ossification was
      observed outside the cyst on the forehead. We speculated that chronic
      inflammation caused ossification around the cyst. Therefore, epidermal cyst
      should be included in the differential diagnosis of cysts with ossification. 

PMID- 25067880
TI  - Modified six-minute walk test: number of steps per second.
AB  - The 6-min walk test (6MWT) has been used to examine subjective dyspnea, predict
      mortality and measure clinical outcomes in studies of patients with chronic
      pulmonary or heart disease. Although the 6MWT is useful to assess the general
      ability to perform daily physical activity, it is difficult to evaluate time
      dependent responses. To improve the 6MWT, we devised a new index, which is the
      number of steps walked per second (NSPS). We performed the 6MWT in 11 healthy
      subjects and 7 patients with chronic obstructive pulmonary disease (COPD) and
      calculated the NSPS. The mean NSPS was significantly higher in the healthy
      subjects than in the COPD patients, while the coefficient of variation of the
      NSPS was significantly smaller in healthy subjects compared with COPD patients.
      Calculation of the NSPS was useful to evaluate the walking pattern. This modified
      6MWT may be helpful for assessing the efficacy of rehabilitation and drug therapy
      for COPD. 

PMID- 25067881
TI  - SPATIO-TEMPORAL COMPLEXITY OF THE AORTIC SINUS VORTEX.
AB  - The aortic sinus vortex is a classical flow structure of significant importance
      to aortic valve dynamics and the initiation and progression of calific aortic
      valve disease. We characterize the spatio-temporal characteristics of aortic
      sinus voxtex dynamics in relation to the viscosity of blood analog solution as
      well as heart rate. High resolution time-resolved (2KHz) particle image
      velocimetry was conducted to capture 2D particle streak videos and 2D
      instantaneous velocity and streamlines along the sinus midplane using a
      physiological but rigid aorta model fitted with a porcine bioprosthetic heart
      valve. Blood analog fluids used include a water-glycerin mixture and saline to
      elucidate the sensitivity of vortex dynamics to viscosity. Experiments were
      conducted to record 10 heart beats for each combination of blood analog and heart
      rate condition. Results show that the topological characteristics of the velocity
      field vary in time-scales as revealed using time bin averaged vectors and
      corresponding instantaneous streamlines. There exist small time-scale vortices
      and a large time-scale main vortex. A key flow structure observed is the counter
      vortex at the upstream end of the sinus adjacent to the base (lower half) of the
      leaflet. The spatio-temporal complexity of vortex dynamics is shown to be
      profoundly influenced by strong leaflet flutter during systole with a peak
      frequency of 200Hz and peak amplitude of 4 mm observed in the saline case. While
      fluid viscosity influences the length and time-scales as well as the introduction
      of leaflet flutter, heart rate influences the formation of counter vortex at the
      upstream end of the sinus. Higher heart rates are shown to reduce the strength of
      the counter vortex that can greatly influence the directionality and strength of
      shear stresses along the base of the leaflet. This study demonstrates the impact
      of heart rate and blood analog viscosity on aortic sinus hemodynamics.

PMID- 25067882
TI  - Daily Physical Activity: Relation to Everyday Memory in Adulthood.
AB  - We examined the relationship between daily physical activity and everyday memory
      using an eight-day diary design with young, middle-aged, and older adults.
      Contrary to expectations, age differences were not reported in the frequency of
      memory failures and daily physical activity at the between-person level.
      Multilevel modeling, however, indicated that on days when adults engaged in
      leisure exercise (physical activity performed during leisure or free time) they
      reported fewer memory failures, and this was most apparent for older adults.
      Lagged analyses indicated that when leisure activity was reported on one day,
      fewer memory failures were reported the next day, and this was especially true
      for older adults. Thus, findings demonstrate that the benefits of physical
      activity for memory in later life are observable on a short-term daily basis.

PMID- 25067884
TI  - Examining Individual and Instruction-Related Predictors of the Self-Determination
      of Students with Disabilities: Multiple Regression Analyses.
AB  - This study examined individual and instructional predictors of the self
      determination of students with disabilities, as measured by The Arc's Self
      Determination Scale and the AIR Self-Determination Scale, Student version. The
      general findings indicated that instructional, knowledge and dispositional
      factors predicted students' self-determination over personal predictor variables.
      In particular, self-efficacy and outcome expectancy scores, student-directed
      transition planning instruction, and students' pre-intervention transition
      planning knowledge predicted higher students' self-determination.

PMID- 25067883
TI  - Distinct Stress and Resource Profiles Among At-Risk Adolescents: Implications for
      Violence and Other Problem Behaviors.
AB  - This study tests for the presence of subgroups among youth at-risk for school
      drop-out and whether those groups differ on levels of violence and related
      problem behaviors. Latent profile analysis was employed with a diverse adolescent
      sample (N = 849) to identify and describe subgroups based on assessment of stress
      and coping resources, resulting in four distinct groups: Low Risk, Unprotected,
      Risk Only, and High Risk. Tests across these groups demonstrated significant
      heterogeneity in violent behaviors, substance use, and school disengagement. The
      value of stress and protective resource assessment and tailoring interventions to
      meet the differing needs of vulnerable youth is discussed.

PMID- 25067885
TI  - Test Framing Generates a Stability Bias for Predictions of Learning by Causing
      People to Discount their Learning Beliefs.
AB  - People estimate minimal changes in learning when making predictions of learning
      (POLs) for future study opportunities despite later showing increased performance
      and an awareness of that increase (Kornell & Bjork, 2009). This phenomenon is
      conceptualized as a stability bias in judgments about learning. We investigated
      the malleability of this effect, and whether it reflected people's underlying
      beliefs about learning. We manipulated prediction framing to emphasize the role
      of testing vs. studying on memory and directly measured beliefs about multi-trial
      study effects on learning by having participants construct predicted learning
      curves before and after the experiment. Mean POLs were more sensitive to the
      number of study-test opportunities when performance was framed in terms of study
      benefits rather than testing benefits and POLs reflected pre-existing beliefs
      about learning. The stability bias is partially due to framing and reflects
      discounted beliefs about learning benefits rather than inherent belief in the
      stability of performance.

PMID- 25067887
TI  - Controlling Degradation of Hydrogels via the Size of Cross-Linked Junctions.

PMID- 25067886
TI  - Effectiveness of Cognitive/Behavioral Small Group Intervention for Reduction of
      Depression and Stress in Non-Hispanic White and Hispanic/Latino Women Dementia
      Family Caregivers: Outcomes and Mediators of Change.
AB  - This study enrolled 184 middle-aged and older women (95 Non-Hispanic White and 89
      Hispanic/Latino) who provided in-home hands-on care to an elderly relative with
      Alzheimer's disease or another form of dementia. Within ethnic group they were
      randomly assigned to either a CBT-based small group intervention program called
      "Coping with Caregiving" (CWC) that taught a variety of cognitive and behavioral
      skills to reduce stress and depression, or to a minimal telephone based control
      condition (TSC). Intervention lasted about 4 months; one post-treatment
      assessment was completed 6 months after baseline by interviewers blind to the
      intervention condition. Interviews and interventions were conducted in English or
      Spanish by trained staff. Results indicated that those in the CWC (regardless of
      ethnicity) showed greater improvement from pre to post intervention than those in
      the TSC on measures of depressive symptoms, overall life stress, and caregiving
      specific stress. In order to investigate if these changes may have been related
      to one proposed mechanism of change in CBT (skill utilization), a new measure was
      constructed. Change in frequency of use and perceived helpfulness of adaptive
      coping skills were assessed in all caregivers. Results indicated that caregivers
      in CWC reported greater frequency of use, and greater perceived helpfulness, of
      these skills at post intervention compared to caregivers in the TSC. Improvement
      measured by dependent measures was correlated with an increase in these indices
      for those in the CWC. Tests for mediation suggest that effective skill
      utilization may mediate the effect of treatment on outcome. Implications of these
      findings are discussed and recommendations provided for future research.

PMID- 25067888
TI  - Evaluation of attempted suicide in emergency departments in Sanliurfa province,
      southeastern Turkey.
AB  - AIM: Attempted suicide is one of the most important public health problems among
      preventable causes of mortality in the general population. Identifying risk
      factors for the prevention of suicide is a major public health goal. The aim of
      this study was to determine the annual rate of attempted suicide, related risk
      factors, and interventions, among referrals to emergency departments in the
      Sanliurfa province of southeastern Turkey. SUBJECTS AND METHODS: Data were
      obtained from all emergency departments in the province based on the 'Suicide
      Attempt Registry' standardized records for the calendar year 2010.
      Sociodemographic characteristics, aetiology, psychiatric history, psychiatric
      consultations, and interventions were examined. The groups were analysed with the
      chi-square test; the significance level was set at p<0.05. RESULTS: The annual
      rate of suicide attempts was 55.39 in 100,000 for the calendar year 2010. The
      rate was 3.47 times higher among women than men, and in particular 4.15 times
      higher for the 15-24 year age group among women than in men with the highest
      incidence of suicide attempts. The majority of cases were referred in April and
      May. Medication or toxic agent ingestions comprised 90.3 % of cases. The main
      reason for attempts was family problems or domestic violence among women, and
      economic hardships among men, and rates of physical and mental problems were
      similar for both sexes. Only 8.8 % of cases were subsequently referred for
      psychiatric consultation. Among cases with a prior suicide attempt history, 44.6
      % had a reported psychiatric disorder. CONCLUSION: The results of this
      investigation show that strengthening of surveillance and emergency healthcare
      systems, enhancement of mental health literacy, and inter-sector collaboration
      for development of community empowerment programmes are of vital importance for
      prevention of attempted suicide. The low rate of psychiatric referrals for
      subsequent intervention represented a major gap in urgent mental health services
      in the region.

PMID- 25067889
TI  - The 'Dangerous' Women of Animal Welfare: How British Veterinary Medicine Went to
      the Dogs.
AB  - This paper examines the turn toward the small companion animal that occurred in
      British veterinary medicine in the twentieth century. The change in species
      emphasis is usually attributed to post-war socioeconomic factors, however this
      explanation ignores the extensive small animal treatment that was occurring
      outwith the veterinary profession in the interwar period. The success of this
      unqualified practice caused the veterinary profession to rethink attitudes to
      small animals (dogs initially, later cats) upon the decline of horse practice.
      This paper argues that a shift toward seeing the small animal as a legitimate
      veterinary patient was necessary before the specialty could become mainstream in
      the post-war years, and that this occurred between the wars as a result of the
      activities of British animal welfare charities, especially the People's
      Dispensary for Sick Animals of the Poor.

PMID- 25067890
TI  - The Prevalence of Syphilis in England and Wales on the Eve of the Great War: Re
      visiting the Estimates of the Royal Commission on Venereal Diseases 1913-1916.
AB  - Public fears of widespread venereal disease led in 1913 to the appointment of The
      Royal Commission on Venereal Diseases (RCVD). In 1916 its Final Report offered
      only a single cautious and somewhat imprecise summary statement about the likely
      prevalence of venereal diseases in England and Wales. Although the significance
      of contemporary attitudes to venereal disease has attracted a good deal of
      historiographic attention, no historian or demographer has since investigated
      this aspect of the Royal Commission's work. This article critically re-examines
      the most important quantitative evidence presented to the Royal Commission
      relating to the years immediately prior to the First World War. It utilises this
      evidence to produce new estimates of the probable prevalence of syphilis among
      adult males, both nationally and among certain geographical divisions and social
      groups in the national population; and also to offer a comment on the likely
      prevalence of gonorrhoea.

PMID- 25067891
TI  - The Machinery of Authoritarian Care: Dramatising Breast Cancer Treatment in 1970s
      Britain.
AB  - This article examines the professional and public response to the television play
      Through the Night, which aired on BBC1 in December 1975. One of the first British
      mass media portrayals of a woman's experience being treated for breast cancer,
      this play attracted a large audience and considerable attention from both critics
      and everyday viewers. My analysis of the play draws on sources documenting expert
      responses to the play in its production stages, as well as critics' and viewers'
      responses to what the play said about breast cancer treatment in particular, and
      about Britons' experiences of medical institutions more broadly. Together, I
      argue, these sources help us see how Through the Night's critique of what one
      expert called 'the machinery of authoritarian care' reverberated with and
      supported the efforts of professionals anxious to improve patient experience, and
      how it crystallised the concerns of activists and everyday viewers.

PMID- 25067893
TI  - Erratum: Intermittent Right Ventricular Outflow Tract Capture due to Chronic
      Right Atrial Lead Dislodgement.
AB  - [This corrects the article on p. 217 in vol. 14, PMID: 25057224.]. 

PMID- 25067894
TI  - Content and Perceived Utility of Mental Imagery by Older Adults in a Peer
      Delivered Physical Activity Intervention.
AB  - Imagery interventions intended to increase exercise behavior are rare. The Active
      Adult Mentoring Program (AAMP) was a randomized controlled trial with imagery
      content. The purposes of this study were to examine the content and perceived
      utility of mental imagery with 24 AAMP participants (Mage = 65.00, SD = 8.79
      years). Digital recordings of AAMP sessions and post-intervention interviews were
      content-analyzed. Emergent themes included images of the physical activity
      context and negative impressions about imagery. Post-intervention interviews
      revealed that 13 participants reported positive experiences using mental imagery
      while 9 would not engage in further use. Important implications are discussed.

PMID- 25067892
TI  - A material's point of view on recent developments of polymeric biomaterials:
      control of mechanical and biochemical properties.
AB  - Cells respond to a variety of stimuli, including biochemical, topographical and
      mechanical signals originating from their micro-environment. Cell responses to
      the mechanical properties of their substrates have been increasingly studied for
      about 14 years. To this end, several types of materials based on synthetic and
      natural polymers have been developed. Presentation of biochemical ligands to the
      cells is also important to provide additional functionalities or more selectivity
      in the details of cell/material interaction. In this review article, we will
      emphasize the development of synthetic and natural polymeric materials with well
      characterized and tunable mechanical properties. We will also highlight how
      biochemical signals can be presented to the cells by combining them with these
      biomaterials. Such developments in materials science are not only important for
      fundamental biophysical studies on cell/material interactions but also for the
      design of a new generation of advanced and highly functional biomaterials.

PMID- 25067895
TI  - The Effect of Social and Classroom Ecological Factors on Promoting Self
      Determination in Elementary School.
AB  - Promoting the self-determination of students with disabilities as a means to
      access the general curriculum has been the subject of research in recent years,
      as has the importance of efforts to promote self-determination during elementary
      years. To examine the status of such efforts in the field, 203 elementary special
      educators were surveyed in 23 states to determine how (a) classroom instructional
      practices or strategies, (b) classroom ecological or setting variables, and (c)
      self-reported barriers to promoting self-determination affected their perceptions
      of the importance of teaching self-determination and the frequency with which
      they did so. Results indicated that special educators' perceived importance of
      teaching self-determination was not impacted by classroom instructional factors,
      but was affected by classroom ecological factors. Classroom ecological factors
      were not, however, significant in the frequency with which teachers provided
      instruction on self-determination, but classroom instructional practices were.
      Limitations and implications are discussed, and suggestions for future research
      are offered.

PMID- 25067896
TI  - Adolescents Exiting Homelessness Over Two Years: The Risk Amplification and
      Abatement Model.
AB  - The Risk Amplification and Abatement Model (RAAM), demonstrates that negative
      contact with socializing agents amplify risk, while positive contact abates risk
      for homeless adolescents. To test this model, the likelihood of exiting
      homelessness and returning to familial housing at 2 years and stably exiting over
      time are examined with longitudinal data collected from 183 newly homeless
      adolescents followed over 2 years in Los Angeles, CA. In support of RAAM,
      unadjusted odds of exiting at 2 years and stably exiting over2 years revealed
      that engagement with pro-social peers, maternal social support, and continued
      school attendance all promoted exiting behaviors. Simultaneously, exposure to
      family violence and reliance on shelter services discouraged stably exiting
      behaviors. Implications for family-based interventions are proposed.

PMID- 25067898
TI  - Reply to evolutionary flux of canonical microRNAs and mirtrons in Drosophila.

PMID- 25067897
TI  - Disasters and Depressive Symptoms in Children: A Review.
AB  - BACKGROUND: Disasters are destructive, potentially traumatic events that affect
      millions of youth each year. OBJECTIVE: The purpose of this paper was to review
      the literature on depressive symptoms among youth after disasters. Specifically,
      we examined the prevalence of depression, risk factors associated with depressive
      symptoms, and theories utilized in this research area. METHODS: We searched
      MEDLINE, PsycInfo, and PubMed electronic databases for English language articles
      published up to May 1, 2013. Reference lists from included studies were reviewed
      to capture additional studies. Only quantitative, peer reviewed studies,
      conducted with youth under the age of 18 years, that examined postdisaster
      depressive symptoms were included. Seventy-two studies met inclusion criteria.
      Prevalence of depressive symptoms, disaster type, correlates of depressive
      symptoms, and theories of depressive symptoms were reviewed. RESULTS: Only 27
      studies (38%) reported on prevalence rates among youth in their sample.
      Prevalence rates of depression among youth postdisaster ranged from 2% to 69%.
      Potential risk factors were identified (e.g., female gender, exposure stressors,
      posttraumatic stress symptoms). Theories were examined in less than one-third of
      studies (k = 21). CONCLUSIONS: Given the variability in prevalence rates,
      difficulty identifying a single profile of youth at risk for developing
      depressive symptoms, and lack of a unifying theory emerging from the studies,
      recommendations for future research are discussed. Use of established batteries
      of assessments could enable comparisons across studies. Merging existing theories
      from children's postdisaster and depression literatures could aid in the
      identification of risk factors and causal pathways.

PMID- 25067899
TI  - Influence of Cofactor Regeneration Strategies on Preparative-Scale, Asymmetric
      Carbonyl Reductions by Engineered Escherichia coli.
AB  - This study was designed to determine whether whole cells or crude enzyme extracts
      are more effective for preparative-scale ketone reductions by dehydrogenases as
      well as learning which cofactor regeneration scheme is most effective. Based on
      results from three representative ketone substrates (an alpha-fluoro-beta-keto
      ester, a bis-trifluoromethylated acetophenone, and a symmetrical beta-diketone),
      our results demonstrate that several nicotinamide cofactor regeneration
      strategies can be applied to preparative-scale dehydrogenase-catalyzed reactions
      successfully.

PMID- 25067900
TI  - Defining and Identifying Members of a Research Study Population: CTSA-Affiliated
      Faculty Members.

PMID- 25067901
TI  - Associations of hypomelanotic skin disorders with autism: Do they reflect the
      effects of genetic mutations and epigenetic factors on vitamin-D metabolism in
      individuals at risk for autism?
AB  - Vitamin D is crucial for full functioning in many genes, and vitamin-D deficiency
      interferes with many processes, including brain development and DNA repair.
      Several lines of evidence suggest that prenatal and early postnatal vitamin-D
      deficiency increases risk for autism, probably through multiple effects that
      include impaired brain development and increased de novo mutations. High rates of
      autism in several genetically based hypomelanotic skin disorders present a
      puzzle, because ultraviolet-B (UVB) radiation acting on skin is the major natural
      source of vitamin D, and lighter skin, which increases UVB penetration, helps
      protect against vitamin-D deficiency, especially at higher latitudes.
      Understanding autism's association with hypomelanosis may elucidate autism's
      etiology. We consider two hypotheses that may help explain autism's association
      with hypomelanotic disorders. Hypothesis 1) Because genetic and epigenetic
      variants that produce hypomelanotic conditions may help protect against vitamin-D
      deficiency, especially at higher latitudes, these variants may tend to decrease
      mortality - and increase the fertility - of individuals who also carry genetic or
      epigenetic factors that increase vulnerability to autism. Hypothesis 2) Children
      with hypomelanotic conditions will be more likely to develop autism, because
      children's photosensitivity and parental concerns about sunburn and skin cancer
      lead them to excessively reduce children's sun exposure and resultant vitamin-D
      levels. One approach to testing these hypotheses would involve comparing the
      genomes, epigenetic markers, skin pigmentation, and serum and brain levels of the
      active form of vitamin D in autistic individuals, with and without co-morbid
      hypomelanoses, as well as in their relatives and controls. Because availability
      of UVB radiation varies widely around the world, epidemiological and genetic
      studies of the co-morbidity in different regions would provide complementary
      means of testing the hypotheses. If test results support either hypothesis, they
      will add important evidence for an etiologic role of vitamin-D deficiency in
      autism, as well as supporting investigation of whether vitamin-D enhancement may
      aid treatment and prevention of autism.

PMID- 25067902
TI  - Enhanced solubility and intestinal absorption of candesartan cilexetil solid
      dispersions using everted rat intestinal sacs.
AB  - OBJECTIVE: Candesartan cilexetil (CAN) is a poor aqueous soluble compound and a P
      glycoprotein (P-gp) efflux pump substrate. These key factors are responsible for
      its incomplete intestinal absorption. METHODS: In this study, we investigated to
      enhance the absorption of CAN by improving its solubility and inhibiting
      intestinal P-gp activity. A phase solubility method was used to evaluate the
      aqueous solubility of CAN in PVP K30 (0.2-2%). Gibbs free energy [Formula: see
      text] values were all negative. Solubility was enhanced by the freeze drying
      technique. The in vitro dissolution was evaluated using the USP paddle method.
      The interaction between drug and carrier was evaluated by Fourier transform
      infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Differential scanning
      calorimetry (DSC) studies. Naringin was selected as P-gp inhibitor. Absorption
      studies were performed using the everted gut sac model from rat jejunum. The drug
      analysis was performed by HPLC. RESULTS: FTIR spectra revealed no interaction
      between drug and PVP K30. From XRD and DSC data, CAN was in the amorphous form,
      which explains the cumulative release of drug from its prepared systems. We
      noticed an enhancement of CAN absorption by improving its solubility and
      inhibiting the P-gp activity. The significant results (p < 0.05) were obtained
      for freeze dried solid dispersions in the presence of P-gp inhibitor than without
      naringin (15 mg/kg) with an absorption enhancement of 8-fold. CONCLUSION:
      Naringin, a natural flavonoid, has no undesirable side effects. Therefore, it
      could be employed as an excipient in the form of solid dispersions to increase
      CAN intestinal absorption and its oral bioavailability.

PMID- 25067903
TI  - Anaphylaxis to lidocaine with tolerance to articaine in a 12 year old girl.
AB  - True allergic reactions to local anesthetics are extremely rare and constitute
      less than 1% of all reactions. In addition, many of those allergic reactions are
      caused by the preservative constituents of the local anesthetics. Here we report
      a 12 year old girl with anaphylaxis to lidocaine (an amide local anesthetic) on
      two occasions. The allergy was confirmed by positive skin prick test to the drug.
      Skin testing and challenge to another amide local anesthetic (articaine) were
      negative. Subsequently, its use was well tolerated in a dental procedure. Up to
      our knowledge, this is the first report of a patient who is allergic to lidocaine
      and tolerant to articaine. 

PMID- 25067904
TI  - Asynchrony of taxonomic, functional and phylogenetic diversity in birds.
AB  - AIM: We assessed the temporal trends of taxonomic, functional and phylogenetic
      diversities in the French avifauna over the last two decades. Additionally, we
      investigated whether and how this multifaceted approach to biodiversity dynamics
      can reveal an increasing similarity of local assemblages in terms of species,
      traits and/or lineages. LOCATION: France. METHODS: We analysed a large-scale
      dataset that recorded annual changes in the abundance of 116 breeding birds in
      France between 1989 and 2012. We decomposed and analysed the spatio-temporal
      dynamics of taxonomic, phylogenetic and functional diversities and each of their
      alpha-, beta- and gamma-components. We also calculated the trend in the mean
      specialization of bird communities to track the relative success of specialist
      versus generalist species within communities during the same period. RESULTS: We
      found large variation within and among the temporal trends of each biodiversity
      facet. On average, we found a marked increase in species and phylogenetic
      diversity over the period considered, but no particular trend was found for
      functional diversity. Conversely, changes in beta-diversities for the three
      facets were characterized by independent and nonlinear trends. We also found a
      general increase in the local occurrence and abundance of generalist species
      within local communities. MAIN CONCLUSIONS: These results highlight a relative
      asynchrony of the different biodiversity facets occurring at large spatial
      scales. We show why a multifaceted approach to biodiversity dynamics is needed to
      better describe and understand changes in community composition in macroecology
      and conservation biogeography.

PMID- 25067905
TI  - Behavioural therapies versus other psychological therapies for depression.
AB  - This is the protocol for a review and there is no abstract. The objectives are as
      follows: To examine the effectiveness and acceptability of all BT approaches
      compared with all other psychological therapy approaches for acute depressionTo
      examine the effectiveness and acceptability of different BT approaches
      (behavioural therapy, behavioural activation, social skills training and
      relaxation training) compared with all other psychological therapy approaches for
      acute depression.To examine the effectiveness and acceptability of all BT
      approaches compared with different psychological therapy approaches
      (psychodynamic, humanistic, integrative, cognitive-behavioural and third wave
      CBT) for acute depression.

PMID- 25067906
TI  - Mindfulness-based 'third wave' cognitive and behavioural therapies versus other
      psychological therapies for depression.
AB  - This is the protocol for a review and there is no abstract. The objectives are as
      follows: To examine the effectiveness and acceptability of all third wave CBT
      approaches compared with all other psychological therapy approaches for acute
      depression.To examine the effectiveness and acceptability of different third wave
      CBT approaches (ACT,compassionate mind training, functional analytic
      psychotherapy, extended behavioural activation and meta-cognitive therapy)
      compared with all other psychological therapy approaches for acute depression.To
      examine the effectiveness and acceptability of all third wave CBT approaches
      compared with different psychological therapy approaches (psychodynamic,
      behavioural, humanistic, integrative, cognitive-behavioural) for acute
      depression.

PMID- 25067907
TI  - Mindfulness-based 'third wave' cognitive and behavioural therapies versus
      treatment as usual for depression.
AB  - This is the protocol for a review and there is no abstract. The objectives are as
      follows: To examine the effectiveness and acceptability of all third wave CBT
      approaches compared with treatment as usual/waiting list/attention placebo
      control conditions for acute depression.To examine the effectiveness and
      acceptability of different third wave CBT approaches (ACT, compassionate mind
      training, functional analytic psychotherapy, meta-cognitive therapy, dialectical
      behaviour therapy, MBCT, extended behavioural activation and meta-cognitive
      therapy) compared with treatment as usual/waiting list/attention placebo control
      conditions for acute depression.To examine the effectiveness and acceptability of
      all third wave CBT approaches compared with different types of comparator
      (standard care, no treatment, waiting list, attention placebo) for acute
      depression.

PMID- 25067908
TI  - Creating an advance-care-planning decision aid for high-risk surgery: a
      qualitative study.
AB  - BACKGROUND: High-risk surgery patients may lose decision-making capacity as a
      result of surgical complications. Advance care planning prior to surgery may be
      beneficial, but remains controversial and is hindered by a lack of appropriate
      decision aids. This study sought to examine stakeholders' views on the
      appropriateness of using decision aids, in general, to support advance care
      planning among high-risk surgery populations and the design of such a decision
      aid. METHODS: Key informants were recruited through purposive and snowball
      sampling. Semi-structured interviews were conducted by phone until data collected
      reached theoretical saturation. Key informants were asked to discuss their
      thoughts about advance care planning and interventions to support advance care
      planning, particularly for this population. Researchers took de-identified notes
      that were analyzed for emerging concordant, discordant, and recurrent themes
      using interpretative phenomenological analysis. RESULTS: Key informants described
      the importance of initiating advance care planning preoperatively, despite
      potential challenges present in surgical settings. In general, decision aids were
      viewed as an appropriate approach to support advance care planning for this
      population. A recipe emerged from the data that outlines tools, ingredients, and
      tips for success that are needed to design an advance care planning decision aid
      for high-risk surgical settings. CONCLUSIONS: Stakeholders supported
      incorporating advance care planning in high-risk surgical settings and endorsed
      the appropriateness of using decision aids to do so. Findings will inform the
      next stages of developing the first advance care planning decision aid for high
      risk surgery patients.

PMID- 25067909
TI  - A simple and cost-effective method of DNA extraction from small formalin-fixed
      paraffin-embedded tissue for molecular oncologic testing.
AB  - BACKGROUND: Extraction of DNA from formalin-fixed, paraffin-embedded (FFPE)
      tissue is a critical step in molecular oncologic testing. As molecular oncology
      testing becomes more important for prognostic and therapeutic decision making and
      tissue specimens become smaller due to earlier detection of suspicious lesions
      and the use of fine needle aspiration methods for tissue collection, it becomes
      more challenging for the typical molecular pathology laboratory to obtain
      reliable test results. We developed a DNA extraction method to obtain sufficient
      quantity and high quality genomic DNA from limited FFPE tissue for molecular
      oncology testing using a combination of H&E stained slides, a matrix capture
      method and the Qiagen DNA column. METHODS: THREE DNA EXTRACTION METHODS WERE
      COMPARED: our standard procedure of manually scraping tissue from unstained
      slides followed by DNA extraction using the QIAamp FFPE column (Qiagen, Valencia,
      CA), a glue capture method (Pinpoint Solution, Zymo Research Corp, Inc) on H&E
      stained slides followed by DNA extraction using either the QIAamp column or the
      column included with the Pinpoint kit (Zymo Research). The DNA extraction
      protocol was optimized. Statistical analysis was performed using the paired two
      sample student's t-test. RESULTS: The combination of the matrix capture method
      with the QIAamp column gave an equivalent amount of DNA as our standard
      extraction method using the unstained slides and a 4.6-fold higher DNA yield than
      using the Zymo column included in the Pinpoint Slide Solution kit. Several
      molecular tests were performed and DNA purified using the new method gave the
      same results as for the previous methods. CONCLUSIONS: Using H&E stained slides
      allows visual confirmation of tumor cells during microdissection. The Pinpoint
      solution made removal of specific tissue from the slides easier and reduced the
      risk of contamination and tissue loss. This DNA extraction method is simple, cost
      effective, and blends with our current workflow requiring no additional
      equipment.

PMID- 25067910
TI  - Probing SH2-domains using Inhibitor Affinity Purification (IAP).
AB  - BACKGROUND: Many human diseases are correlated with the dysregulation of signal
      transduction processes. One of the most important protein interaction domains in
      the context of signal transduction is the Src homology 2 (SH2) domain that binds
      phosphotyrosine residues. Hence, appropriate methods for the investigation of SH2
      proteins are indispensable in diagnostics and medicinal chemistry. Therefore, an
      affinity resin for the enrichment of all SH2 proteins in one experiment would be
      desirable. However, current methods are unable to address all SH2 proteins
      simultaneously with a single compound or a small array of compounds. RESULTS: In
      order to overcome these limitations for the investigation of this particular
      protein family in future experiments, a dipeptide-derived probe has been
      designed, synthesized and evaluated. This probe successfully enriched 22 SH2
      proteins from mixed cell lysates which contained 50 SH2 proteins. Further
      characterization of the SH2 binding properties of the probe using depletion and
      competition experiments indicated its ability to enrich complexes consisting of
      SH2 domain bearing regulatory PI3K subunits and catalytic phosphoinositide 3
      kinase (PI3K) subunits that have no SH2 domain. CONCLUSION: The results make this
      probe a promising starting point for the development of a mixed affinity resin
      with complete SH2 protein coverage. Moreover, the additional findings render it a
      valuable tool for the evaluation of PI3K complex interrupting inhibitors.

PMID- 25067911
TI  - Relationship between two-year mortality and 30 day to the Hospital Readmission
      from the Nursing Home.
AB  - INTRODUCTION/OBJECTIVE: Hospital readmission from the nursing home is often a
      concerning development for nursing home residents who have recently been
      dismissed from the hospital. Clinicians and family often consider the potential
      prognosis when residents return to the hospital. The objective was to determine
      the relationship between two-year mortality and 30-day hospital readmission
      status from the nursing home. DESIGN/METHODOLOGY: This was a retrospective cohort
      study of all adult patients over 60 living within the nursing home in Olmsted
      County , MN. All residents were impaneled within a primary care practice. Of this
      initial nursing home cohort, the residents was then divided into those residents
      who were readmitted to the hospital within 30 days and those who were not
      readmitted. The primary outcome was mortality within 2 years of 1/1/05. Data
      analysis involved Pearson's chi square analysis for the proportional variables.
      RESULTS: There were 12,650 patients within the initial panel of which 2261 were
      admitted to the nursing home. Of this 2261 cohort, 347 residents (15.3%) were
      readmitted to the hospital within 30 days. Of the 347 readmitted, 106 residents
      died within 2 years (31%) versus 293 (15%) in the group that was not readmitted
      to the hospital (p <0.001) with a hazard ratio of 2.43 [95% CI 1.88-3.16].
      CONCLUSION/DISCUSSION: Older adults who are admitted to the nursing home are at
      significant risk of 2-year mortality with 2.5 times the odds of mortality in 2
      years compared to those residents who are not readmitted. Those patients who are
      readmitted are older which could explain some of this difference or they could
      have significant comorbid illness which explains the higher mortality. When faced
      with residents who have multiple hospital admissions, the provider should
      consider potential discussion of end of life issues and advanced directives given
      the prognosis.

PMID- 25067912
TI  - Independent and Interactive Contributions of Parenting Behaviors and Beliefs in
      the Prediction of Early Childhood Behavior Problems.
AB  - OBJECTIVE: This study examined interactions between parenting beliefs and
      parenting behaviors in the prediction of early childhood externalizing and
      internalizing symptoms. DESIGN: Negative intrusive and sensitive parenting
      behaviors during infancy and toddlerhood were observed in conjunction with self
      reported maternal beliefs about the importance of discipline/control and concerns
      regarding spoiling in a community sample of 185 African American and European
      American mother-child dyads. Multiple regression techniques modeled interactions
      between parenting beliefs and observed behaviors to predict mother-reported
      internalizing and externalizing symptoms at 30 and 36 months. The analyses also
      explored the role of ethnicity as a moderator of these relations. RESULTS: The
      combination of low and average spoiling beliefs and low levels of sensitive
      parenting was associated with elevated internalizing symptoms. Negative parenting
      and beliefs reflecting concerns about spoiling were independent risk factors for
      elevated externalizing symptoms. CONCLUSION: Parenting beliefs and behaviors
      should be considered jointly to identify risks for the development of early
      behavior problems.

PMID- 25067914
TI  - James Yoo, MD, FACS, FASCRS.

PMID- 25067913
TI  - Nanoscale Adhesion Ligand Organization Regulates Osteoblast Proliferation and
      Differentiation.
AB  - It was hypothesized that nanoscale adhesion ligand spacing regulates cell
      adhesion, proliferation, and differentiation, and that this control can be
      decoupled from the overall ligand density. Alginate was chemically modified with
      a peptide containing the cell adhesion sequence arginine-glycine-aspartic acid
      (RGD), and the nanoscale spacing of RGD ligands in alginate gels was varied. A
      decrease in the RGD island spacing from 78 to 36 nm upregulated the proliferation
      rates of MC3T3-E1 cells from 0.59 +/- 0.08 to 0.73 +/- 0.03 day-1 and resulted in
      4-fold increase of the osteocalcin secretion rate. This finding was independent
      of the bulk ligand density of gels. These results indicate that nanoscale ligand
      organization may provide an important variable to regulate cell functions in many
      biomedical applications, including tissue engineering.

PMID- 25067915
TI  - Developing a career in colorectal research.

PMID- 25067916
TI  - Overview: getting involved in research as a busy practicing surgeon.
AB  - To succeed in academic surgery in the current era, it is important that a surgeon
      brings a unique attribute that enhances the mission of the institution beyond the
      scope of surgical mastery and relative value units (RVUs). Given the increasing
      pressure on a surgeon to produce RVUs, how can a prospective surgical scientist
      successfully develop and maintain a research program? The establishment of a
      successful research program requires planning that begins in surgical residency
      and careful decision making along the way with clear focus of goals. This article
      will provide insight into the steps to consider along the way as you work to
      establish your successful research program. 

PMID- 25067917
TI  - Developing a research skill set.
AB  - The recent decades have witnessed a significant expansion in the diversity of
      career paths within academic surgery. Although the skills for providing exemplary
      surgical care and for maintaining a strong work ethic are the foundations of an
      academic surgeon, deliberate career planning and organized acquisition of
      research skills contribute to the success of an academic career. In this article,
      we identify a set of core academic skills and propose a framework for acquiring
      them. We also describe specific career paths within academic surgery and provide
      an overview of the opportunities for acquiring specific skill sets. The
      development of an academic career is challenging, and firm knowledge of the
      personal motivations will sustain and endure the time needed for acquiring the
      needed skills. 

PMID- 25067918
TI  - Academic colorectal surgery job search.
AB  - The field of academic colorectal surgery encompasses a vast array of
      possibilities. Clinical care accompanied by research, teaching, innovation,
      and/or administration provides the foundation for what is considered an academic
      career. For those choosing academic colorectal surgery, the process of finding
      and selecting a first job can provoke much angst. This article describes some
      strategies to approach the academic colorectal job search and provides insight
      into deciding a career focus, exploring relevant positions, weighing specific
      factors, and negotiating your first offer. 

PMID- 25067919
TI  - Establishing a successful basic science research program in colon and rectal
      surgery.
AB  - Although at first glance, the surgeon-scientist appears to be a rare breed in
      today's clinical revenue-driven world, with careful planning and mentorship this
      is still a vibrant career path. If one is considering this avenue, it is
      important to seize even small opportunities to pursue laboratory work during
      training-summers in college and medical school, rotation blocks, and dedicated
      time in the middle of residency. Publications and small grants during these times
      will lay the ground work for future success. When considering a faculty position,
      it is essential to identify a mentorship environment that has a track record for
      success-either in the department of surgery or anywhere in the university.
      Ensuring adequate support from the department of surgery chair and division
      leader is essential. Basic science careers take years for the return in
      investment to be manifested! Also critical is to secure extramural funding early
      in the faculty stint-first foundation grants and then National Institutes of
      Health-mentored scientist funding. Surgeons provide a unique perspective in basic
      science work and it is critical that we continue to support young surgeons in
      this career path. 

PMID- 25067920
TI  - Establishing a successful clinical research program.
AB  - Clinical research (CR) is a natural corollary to clinical surgery. It gives an
      investigator the opportunity to critically review their results and develop new
      strategies. This article covers the critical factors and the important components
      of a successful CR program. The first and most important step is to build a
      dedicated research team to overcome time constraints and enable a surgical
      practice to make CR a priority. With the research team in place, the next step is
      to create a program on the basis of an original idea and new clinical hypotheses.
      This often comes from personal experience supported by a review of the available
      evidence. Randomized controlled (clinical) trials are the most stringent way of
      determining whether a cause-effect relationship exists between the intervention
      and the outcome. In the proper setting, translational research may offer
      additional avenues allowing clinical application of basic science discoveries. 

PMID- 25067921
TI  - Work-life balance: history, costs, and budgeting for balance.
AB  - The concept and difficulties of work-life balance are not unique to surgeons, but
      professional responsibilities make maintaining a work-life balance difficult.
      Consequences of being exclusively career focused include burn out, physical, and
      mental ailments. In addition, physician burn out may hinder optimal patient care
      and incur significant costs on health care in general. Assessing current uses of
      time, allocating goals catered to an individual surgeon, and continual self
      assessment may help balance time, and ideally will help prevent burn out. 

PMID- 25067922
TI  - Building an academic colorectal division.
AB  - Colon and rectal surgery is fully justified as a valid subspecialty within
      academic university health centers, but such formal recognition at the
      organizational level is not the norm. Creating a colon and rectal division within
      a greater department of surgery requires an unfailing commitment to academic
      concepts while promulgating the improvements that come in patient care, research,
      and teaching from a specialty service perspective. The creation of divisional
      identity then opens the door for a strategic process that will grow the division
      even more as well as provide benefits to the institution within which it resides.
      The fundamentals of core values, academic commitment, and shared success
      reinforced by receptive leadership are critical. Attention to culture,
      commitment, collaboration, control, cost, and compensation leads to a successful
      academic division of colon and rectal surgery. 

PMID- 25067923
TI  - The Role of Intrapersonal and Ecodevelopmental Factors in the Lives of Latino
      Alternative High School Youth.
AB  - Despite efforts aimed at achieving health equity, Latino youth continue to
      experience significant health and mental health disparities. The purpose of this
      investigation was to explore the role of intrapersonal and ecodevelopmental
      factors, including family, peer, school, and community, in the lives of Latino
      alternative high school youth residing in the Southwest, United States. Five
      focus groups were implemented with a total of 19 participants. Study findings are
      indicative of an ecology characterized by multiple challenges that have a
      significant impact on the lives of Latino alternative high school youth. Findings
      from this study reinforce that there remains a great need to fully understand the
      scope and influence of intrapersonal and ecodevelopmental factors among Latino
      alternative high school youth to inform the development of culturally-responsive
      social work preventive intervention programs.

PMID- 25067924
TI  - Concerns and challenges in flexible sigmoidoscopy screening.
AB  - In 1992, two well-conducted case-control studies used data from two different
      health maintenance organizations and demonstrated a 59-79% reduction in mortality
      from colorectal cancer (CRC) following exposure to sigmoidoscopy. These studies
      highlight the possibility of reducing mortality from CRC using population-based
      endoscopic screening. The development of fiber optics improved the technology,
      and the ease of performing flexible sigmoidoscopy (FS) with widespread adoption
      of this screening modality. To date, FS is the only endoscopic screening modality
      that has been shown to reduce mortality in randomized clinical trials. This
      article reviews the development of sigmoidoscopy, its use in CRC screening and
      the current reduced role of this proven screening modality, and explores new
      frontiers for population-based FS screening.

PMID- 25067925
TI  - Magnetic resonance imaging findings in juvenile spondyloarthropathy and effects
      of treatment observed on subsequent imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is often used to diagnose and
      monitor treatment effects of juvenile spondyloarthropathy (SpA). Our objective
      was to describe MRI findings in juvenile SpA and determine predictors of active
      sacroiliitis and response to treatment. METHODS: Children who had MRI of the
      sacroiliac (SI) joints and were referred to the pediatric rheumatology clinic
      from 2009 to 2012 were retrospectively studied. The clinical parameters,
      laboratory studies and findings on MRI were collected and a composite score ratio
      (CR) was calculated for both SI joints on each MRI study based on a semi
      quantitative scale that included evaluation of bone marrow edema (BME), synovial
      enhancement (SE), and erosions (ER). The findings on MRI were correlated with
      clinical and laboratory values. RESULTS: 50 subjects who underwent 76 MRI for
      suspected or known SpA were included in the study. Sacroiliitis was seen in 48
      MRIs in 32 subjects. Of the subjects with sacroiliitis, mean age +/- standard
      deviation was 13.7 +/- 2.6 years, 71% were male and 41% were HLA B27 positive. SE
      without BME was seen in 31% cases of sacroiliitis. In subjects with sacroiliitis,
      79% also had hip arthritis and 41% had enthesitis of the pelvic region on MRI. In
      38% of subjects with sacroiliitis, physical exam was not indicative of
      sacroiliitis or hip arthritis. Longitudinal data were available for 13 subjects.
      Sacroiliitis on MRI improved in 9 subjects with the greatest improvement in MRI
      composite score ratio after initiation of etanercept therapy. CR improvement was
      due to improvement of BME and SE components, while the ER score remained the same
      or worsened in all but 1 subject. CONCLUSION: History, physical exam or
      laboratory data may not predict sacroiliitis in children. Magnetic resonance
      imaging plays a valuable role in the initial evaluation and later treatment
      monitoring of children with spondyloarthropathy. Synovial enhancement is
      significantly reduced after treatment, and unlike adults, synovial enhancement
      may be detected without accompanying bone marrow edema, which suggests gadolinium
      contrast may be an important component in the assessment of children with
      spondyloarthropathy.

PMID- 25067926
TI  - Establishing a theoretical basis for research in musculoskeletal epidemiology: a
      proposal for the use of biopsychosocial theory in investigations of back pain and
      smoking.
AB  - OBJECTIVE: This article discusses the need for theoretical foundations in
      epidemiological research of musculoskeletal conditions and suggests the use of
      biopsychosocial theory when designing epidemiological studies. The association
      between smoking and back pain is used as an example. DISCUSSION: Theory-driven
      musculoskeletal epidemiologic research is not common. In the epidemiological
      study of musculoskeletal conditions, there are multiple potential causes of a
      disease or disorder. Classic biomedical theory is not well suited to explain such
      phenomena. Biopsychosocial theory is a means through which investigators might
      formulate hypotheses for testing relationships between smoking, back pain, and
      other variables. Various types of conceptual frameworks and analytical models can
      be informed by biopsychosocial theory. CONCLUSION: Biopsychosocial theory is well
      suited for public health and epidemiological studies on musculoskeletal
      conditions, such as the relation between back pain and smoking, and may be useful
      to address the multivariable inputs for this association. Although it is not a
      perfect model, it provides theoretical guidance to inform the research question,
      an element of research design that is lacking in modern-day epidemiologic
      reports.

PMID- 25067927
TI  - Beyond spinal manipulation: should Medicare expand coverage for chiropractic
      services? A review and commentary on the challenges for policy makers.
AB  - OBJECTIVES: Private insurance plans typically reimburse doctors of chiropractic
      for a range of clinical services, but Medicare reimbursements are restricted to
      spinal manipulation procedures. Medicare pays for evaluations performed by
      medical and osteopathic physicians, nurse practitioners, physician assistants,
      podiatrists, physical therapists, and occupational therapists; however, it does
      not reimburse the same services provided by chiropractic physicians. Advocates
      for expanded coverage of chiropractic services under Medicare cite clinical
      effectiveness and patient satisfaction, whereas critics point to unnecessary
      services, inadequate clinical documentation, and projected cost increases. To
      further inform this debate, the purpose of this commentary is to address the
      following questions: (1) What are the barriers to expand coverage for
      chiropractic services? (2) What could potentially be done to address these
      issues? (3) Is there a rationale for Centers for Medicare and Medicaid Services
      to expand coverage for chiropractic services? METHODS: A literature search was
      conducted of Google and PubMed for peer-reviewed articles and US government
      reports relevant to the provision of chiropractic care under Medicare. We
      reviewed relevant articles and reports to identify key issues concerning the
      expansion of coverage for chiropractic under Medicare, including identification
      of barriers and rationale for expanded coverage. RESULTS: The literature search
      yielded 29 peer-reviewed articles and 7 federal government reports. Our review of
      these documents revealed 3 key barriers to full coverage of chiropractic services
      under Medicare: inadequate documentation of chiropractic claims, possible
      provision of unnecessary preventive care services, and the uncertain costs of
      expanded coverage. Our recommendations to address these barriers include the
      following: individual chiropractic physicians, as well as state and national
      chiropractic organizations, should continue to strengthen efforts to improve
      claims and documentation practices; and additional rigorous
      efficacy/effectiveness research and clinical studies for chiropractic services
      need to be performed. Research of chiropractic services should target the triple
      aim of high-quality care, affordability, and improved health. CONCLUSIONS: The
      barriers that were identified in this study can be addressed. To overcome these
      barriers, the chiropractic profession and individual physicians must assume
      responsibility for correcting deficiencies in compliance and documentation;
      further research needs to be done to evaluate chiropractic services; and
      effectiveness of extended episodes of preventive chiropractic care should be
      rigorously evaluated. Centers for Medicare and Medicaid Services policies related
      to chiropractic reimbursement should be reexamined using the same standards
      applicable to other health care providers. The integration of chiropractic
      physicians as fully engaged Medicare providers has the potential to enhance the
      capacity of the Medicare workforce to care for the growing population. We
      recommend that Medicare policy makers consider limited expansion of Medicare
      coverage to include, at a minimum, reimbursement for evaluation and management
      services by chiropractic physicians.

PMID- 25067928
TI  - Straight chiropractic philosophy as a barrier to Medicare compliance: a
      discussion of 5 incongruent issues.
AB  - OBJECTIVE: The purpose of this commentary is to discuss potential 5 factors
      within straight chiropractic philosophy and practice that may prevent Medicare
      compliance. DISCUSSION: The national Medicare Benefit Policy Manual and the
      Florida Local Coverage Determination were reviewed to identify documentation and
      conceptual issues regarding chiropractic practice. Five Medicare positions were
      contrasted with tenets of straight chiropractic philosophy. Based on Medicare's
      documentation requirements, Medicare defines subluxation and chiropractic
      practice from the perspective of treating spinal pain and related functional
      disability. In contrast, traditional straight chiropractic philosophy is not
      based on the treatment of spinal pain and disability or other symptomatic
      presentations. In this context, 5 potential areas of conflict are discussed.
      CONCLUSION: The Medicare version of chiropractic practice is not consistent with
      traditional straight chiropractic philosophy, which may play a role in preventing
      Medicare compliance. The chiropractic profession may need to consider the fashion
      in which "philosophy" as it relates to technique and practice is presented to
      students and doctors to facilitate compliance with the documentation requirements
      of Medicare.

PMID- 25067930
TI  - The John A. Sweaney Lecture: origins.
AB  - The following is a description of the origins of The John A. Sweaney Lecture,
      which is given at each of the World Federation of Chiropractic's biannual
      assemblies. 

PMID- 25067931
TI  - The John A. Sweaney Lecture: Vilamoura, Portugal, May 2007, given by Dr John A.
      Sweaney. Chiropractic: in pursuit of professionalism.
AB  - The following is The John A. Sweaney Lecture delivered by Dr John A. Sweaney at
      the Biannual Assembly of the World Federation of Chiropractic in Vilamoura,
      Portugal, on May 16, 2007. 

PMID- 25067929
TI  - Weight gain as a consequence of living a modern lifestyle: a discussion of
      barriers to effective weight control and how to overcome them.
AB  - OBJECTIVE: The purpose of this commentary is to discuss modern lifestyle factors
      that promote weight gain and to suggest methods for clinicians to more
      effectively educate patients about weight management. DISCUSSION: Most adults in
      the United States are overweight or obese. Multiple factors related to the modern
      lifestyle appear to play causal roles. In general, the population maintains
      sedentary lives and overconsumes calorie-dense foods. In particular, refined
      carbohydrates negatively impact metabolism and stimulate neural addiction
      mechanisms, which facilitate weight gain. As adipose tissue mass accumulates,
      satiation centers in the hypothalamus become resistant to insulin and leptin,
      which leads to increased caloric consumption. Several behavior issues further
      augment weight gain, such as eating too quickly, a lack of sleep, high stress
      levels, and a lack of exercise. Finally, adipose tissue accumulation alters the
      body weight set point, which leads to metabolic changes that function to resist
      weight loss efforts. Each of these factors may work together to augment weight
      gain and promote obesity. Health care providers, such as chiropractic physicians,
      who educate patients on wellness, prevention, and lifestyle changes are well
      positioned to address these issues. CONCLUSION: People need to be educated about
      the modern lifestyle factors that prevent effective weight management. Without
      this knowledge and the associated practical application of lifestyle choices that
      prevent weight gain, becoming overweight or obese appears to be an unavoidable
      consequence of living a modern lifestyle.

PMID- 25067932
TI  - The John A. Sweaney Lecture: Durbin, South Africa, April 2013, given by Dr Louis
      Sportelli. The 100 year test: can that tell us something?
AB  - The following is The John A. Sweaney Lecture delivered by Dr Louis Sportelli at
      the Biannual Assembly of the World Federation of Chiropractic in Durban, South
      Africa, on April 12, 2013. 

PMID- 25067933
TI  - Efficient network meta-analysis: a confidence distribution approach.
AB  - Network meta-analysis synthesizes several studies of multiple treatment
      comparisons to simultaneously provide inference for all treatments in the
      network. It can often strengthen inference on pairwise comparisons by borrowing
      evidence from other comparisons in the network. Current network meta-analysis
      approaches are derived from either conventional pairwise meta-analysis or
      hierarchical Bayesian methods. This paper introduces a new approach for network
      meta-analysis by combining confidence distributions (CDs). Instead of combining
      point estimators from individual studies in the conventional approach, the new
      approach combines CDs which contain richer information than point estimators and
      thus achieves greater efficiency in its inference. The proposed CD approach can e
      ciently integrate all studies in the network and provide inference for all
      treatments even when individual studies contain only comparisons of subsets of
      the treatments. Through numerical studies with real and simulated data sets, the
      proposed approach is shown to outperform or at least equal the traditional
      pairwise meta-analysis and a commonly used Bayesian hierarchical model. Although
      the Bayesian approach may yield comparable results with a suitably chosen prior,
      it is highly sensitive to the choice of priors (especially the prior of the
      between-trial covariance structure), which is often subjective. The CD approach
      is a general frequentist approach and is prior-free. Moreover, it can always
      provide a proper inference for all the treatment effects regardless of the
      between-trial covariance structure.

PMID- 25067934
TI  - Daily Variation of Serum Acylcarnitines and Amino Acids.
AB  - To characterize daily variation of amino acids (AAs) and acylcarnitines (ACs) in
      response to feeding and activity, we measured serum metabolites at various times
      and after various activities during the day. Subjects were admitted overnight for
      serial serum sampling, collected in the evening (6-8pm, n=40), before rising from
      bed or eating (8AM, n=40), 1 hour after rising but before eating (9 AM, n=20), 1
      2 hours after rising and breakfast (9-10 AM, n=40), and at noon (12 PM, n=20).
      Measurements of 15 AAs and 45 ACs were performed by quantitative tandem mass
      spectrometry using stable-isotope dilution. Coefficients of variation within and
      between patients were calculated for individual metabolite values and factors
      derived from principal components analysis. The change of state between
      timepoints was evaluated by nearest neighbor non-parametric analysis of values at
      one timepoint compared to the next subsequent value. Relative to baseline AM
      recumbent concentrations, AA concentrations rose after activity and feeding while
      AC concentrations rose after activity and decreased with feeding. Furthermore,
      for all AAs, ACs, and their factors, biological variation was quantifiably
      evident and distinct from daily variation. This study confirms the daily
      variation of AAs and provides the first report of daily variation for a large
      panel of ACs. Although standardization of sample collection is highly desirable
      to control for daily variation (within a subject due to activity or feeding),
      this study demonstrated measurable biological variability (across subjects)
      suggesting that non-standardized sample collections could potentially provide
      insights into specific AA and AC metabolic pathways and disease mechanisms.

PMID- 25067936
TI  - Serum biochemical assessment of hepatic and renal functions of rats during oral
      exposure to glyphosate with zinc.
AB  - A subchronic toxicity study was carried out to assess hepatic and renal functions
      of rats during oral exposure to glyphosate with zinc for the period of 8 weeks.
      Forty-eight Wistar rats used for the study were randomized into six groups of
      eight Wistar rats each, and each group had equal number of male and female Wistar
      rats. The Wistar rats administered with distilled water at 2 ml/kg body weight
      served as the control group (DW); others were administered with zinc at 50 mg/kg
      body weight (Z) group, glyphosate at 375 mg/kg body weight (G) group, a
      combination of zinc and glyphosate at 50 and 375 mg/kg body weight, respectively
      (Z + G), group, glyphosate at 14.4 mg/kg body weight (GC) group, and a
      combination of zinc and glyphosate at 50 and 14.4 mg/kg body weight, respectively
      (Z + GC), group. At the end of the study, blood samples were collected from each
      rats; from which, sera samples were obtained and assayed for total protein,
      albumin, alanine and aspartate aminotransferases, alkaline phosphatase, Na+, K+,
      Cl-, [Formula: see text], Ca2+, [Formula: see text], urea and creatinine using
      autoanalyzer, and globulin was calculated. The albumin concentration was
      significantly high (p < 0.05) in GC group compared to DW group, and this change
      was ameliorated following supplementation with zinc. The total protein and
      globulin concentrations did not differ significantly between the groups (p >
      0.05), and the relative changes were ameliorated by supplementation with zinc.
      The alkaline phosphatase activity was relatively low in GC group; however,
      supplementation with zinc in Z + GC group made it to be significantly high (p <
      0.05) compared to GC group. The alanine and aspartate aminotransferases in G and
      GC groups were relatively high compared to DW group, which were ameliorated by
      supplementation with zinc. The relatively low Ca2+ concentration in G and GC
      groups compared to DW were ameliorated in Z + G group, and it was significantly
      high in Z + GC group at p < 0.01 compared to DW, p < 0.001 compared to G and GC
      groups and p < 0.05 compared to Z + G group. There were only slight changes in
      the electrolytes concentrations (Na+, K+, Cl-, [Formula: see text] and [Formula:
      see text]), which were differentially ameliorated by zinc supplementation. The
      reasons for the various changes recorded were discussed. It was concluded that
      subchronic oral exposure to glyphosate caused both hepatic and renal functions
      toxicity in rats, which were ameliorated by zinc supplementation.

PMID- 25067937
TI  - Effects of the Chemokine Receptor 5 (CCR5)-Delta32 Mutation on Hepatitis C Virus
      Specific Immune Responses and Liver Tissue Pathology in HCV Infected Patients.
AB  - BACKGROUND: The specific antiviral T cells provide CC chemokine receptor 5 (CCR5)
      for the immune response during the hepatitis C virus (HCV) infection.
      Heterogenous and/or homozygous 32 base pair deletion in CCR5 gene (CCR5Delta32
      bpdel) leads to reduced protein expression. OBJECTIVES: In the current case
      control study, we aimed to compare the histopathological findings of liver to the
      CCR5Delta32 bpdel mutation profiles, expression and some other clinical findings
      in patients with chronic HCV infection. MATERIALS AND METHODS: Multiple Strip
      Assay reverse hybridisation and Real Time PCR techniques were used to determine
      the germline CCR5 mutations and immunohistochemical technique was used to
      evaluate the gene expression in targer tissue biopsies. RESULTS: Target CCR5
      WT/WT, WT/Delta32, and Delta32/Delta32 genotypes were observed in 91.4%, 8.6% and
      0.0% for HCV positive patients and 98.3%, 1.7% and 0.0% for control group
      respectively. The histologic activity index (HAI) was significantly lower (4.0 +/
      1.0) in the mutated group than the non-mutated group (5.7 +/- 1.0). Decreased
      fibrosis levels were detected in HCV positive mutated group. CONCLUSIONS: Results
      showed that CCR5 polymorphism was more frequent in HCV positive patients than in
      healthy population in Turkish population. Current results also showed that
      mutated CCR5 signalling pathway due to CCR5-Delta32 may potentially result in
      subtle reduction of HCV specifity to the drug responses due to the positive
      impact on liver inflammation, fibrosis levels and liver destruction in HCV
      infection.

PMID- 25067938
TI  - Can HCV core ag testing replace the routine screening assays in patients on
      hemodialysis?

PMID- 25067935
TI  - Polymer-Based Nitric Oxide Therapies: Recent Insights for Biomedical
      Applications.
AB  - Since the discovery of nitric oxide (NO) in the 1980s, this cellular messenger
      has been shown to participate in diverse biological processes such as
      cardiovascular homeostasis, immune response, wound healing, bone metabolism, and
      neurotransmission. Its beneficial effects have prompted increased research in the
      past two decades, with a focus on the development of materials that can locally
      release NO. However, significant limitations arise when applying these materials
      to biomedical applications. This Feature Article focuses on the development of NO
      releasing and NO-generating polymeric materials (2006-2011) with emphasis on
      recent in vivo applications. Results are compared and discussed in terms of NO
      dose, release kinetics, and biological effects, in order to provide a foundation
      to design and evaluate new NO therapies.

PMID- 25067939
TI  - Treatment of occult hepatitis C virus infection: does it need special attention?

PMID- 25067940
TI  - Prevalence of risk factors for breast cancer in German airline cabin crew: a
      cross-sectional study.
AB  - BACKGROUND: Many epidemiological studies point to an increased risk of breast
      cancer among female airline cabin crew. Possible causes include occupational
      factors (e.g. cosmic radiation exposure, chronodisruption), as well as lifestyle
      and reproductive factors. AIMS: To investigate the frequency of various risk
      factors in German flight attendants which are recognised to be associated with
      breast cancer. METHODS: 2708 current and former female cabin crew were randomly
      selected by a flight attendants' union and mailed a questionnaire; 1311 responded
      (48% response). Descriptive statistics were used to compare the distribution of
      breast cancer risk factors with general German population data. RESULTS: On
      average, cabin crew were 3.0 cm (95% CI 2.7-3.3) taller than the comparison
      group, while their body mass index was 2.5 kg/m(2) (95% CI 2.4-2.6) lower. We
      found less use of hormone replacement therapy, but longer average use of oral
      contraceptives. Nulliparity among respondents aged 45+ was 57% (95% CI 54%-60%)
      compared to 16%. Average age at first birth was 32.1 years (95% CI 31.7-32.4) vs.
      25.5 years. The birth rate was 0.62 (95% CI 0.58-0.67), less than half the
      population average of 1.34. Alcohol consumption was considerably higher, whereas
      cabin crew tended to smoke less and performed more physical exercise. CONCLUSION:
      We found important differences in terms of anthropometric, gynaecological,
      reproductive and lifestyle factors. Some of these differences (e.g. higher
      nulliparity, alcohol consumption, taller size) could contribute to a higher
      breast cancer risk, whereas others could lead to a reduction (e.g. increased
      physical exercise, lower BMI, less HRT use).

PMID- 25067941
TI  - Biological activities of 'noninfectious' influenza A virus particles.
AB  - Only a small fraction of influenza A virus (IAV) particles within a viral
      population register as infectious by traditional infectivity assays. Despite
      constituting the most abundant product of influenza infection, the role that the
      'noninfectious' particle fraction plays in the biology of the virus has largely
      been ignored. This review shines a light on this oft-ignored population by
      highlighting studies, both old and new, that describe the unique biological
      activities of these particles, and discussing what this population can tell us
      about the biology of IAV evolution and disease.

PMID- 25067943
TI  - Affective Arousal as Information: How Affective Arousal Influences Judgments,
      Learning, and Memory.
AB  - The affect-as-information framework posits that affect is embodied information
      about value and importance. The valence dimension of affect provides evaluative
      information about stimulus objects, which plays a role in judgment and
      decisionmaking. Affect can also provide evaluative information about one's own
      cognitions and response inclinations, information that guides thinking and
      reasoning. In particular, positive affect often promotes, and negative affect
      inhibits, accessible responses or dominant modes of thinking. Affect thus
      moderates many of the textbook phenomena in cognitive psychology. In the current
      review, we suggest additionally that the arousal dimension of affect amplifies
      reactions, leading to intensified evaluations, increased reliance on particular
      styles of learning, and enhanced long-term memory for events. We conclude that
      whereas valenced affective cues serve as information about value, the arousal
      dimension provides information about urgency or importance.

PMID- 25067942
TI  - Bioactive proteins and peptides isolated from Chinese medicines with
      pharmaceutical potential.
AB  - Some protein pharmaceuticals from Chinese medicine have been developed to treat
      cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with
      various pharmacological properties have been successfully isolated from animals
      such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and
      Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from
      species such as Cordyceps militaris, Ganoderma, Momordica cochinchinensis, Viscum
      album, Poria cocos, Senna obtusifolia, Panax notoginseng, Smilax glabra, Ginkgo
      biloba, Dioscorea batatas, and Trichosanthes kirilowii. This article reviews the
      isolation methods, molecular characteristics, bioactivities, pharmacological
      properties, and potential uses of bioactive proteins originating from these
      Chinese medicines. 

PMID- 25067944
TI  - Polyphenols profile and antioxidant activity of skin and pulp of a rare apple
      from Marche region (Italy).
AB  - BACKGROUND: Apples are an important source of polyphenols in the human diet and
      the consumption of this fruit has been linked to the prevention of degenerative
      diseases. RESULTS: CATECHINS, PROCYANIDINS, HYDROXYCINNAMIC ACIDS, FLAVONOL
      GLYCOSIDES, DIHYDROCHALCONE GLYCOSIDES AND ONE ANTHOCYANIN: cyanidin-3-O
      galactoside, were identified both in the peel and pulp. Procyanidins, catechins
      and flavonols represent the main constituents of peel. Concerning the antioxidant
      activity, in the reduction of the stable DPPH radical and in the inhibition of
      lipid peroxidation, the ethanolic extracts of red peel and red pulp showed a good
      similar activity comparable to ascorbic acid in the DPPH test and about ten times
      more active than BHT in the lipoxygenase test, and were much more active than
      aqueous extracts. The ORAC value of red pulp aqueous extract resulted comparable
      to that of red berries: vaccinium, rubus and ribes, foods appreciated for their
      health value. CONCLUSION: This apple contains an appreciable amount of
      polyphenols also in the flesh; this variety with red flesh can also be useful for
      researchers engaged in apples varietal innovation in addition to being used as
      food apple.

PMID- 25067945
TI  - Research highlights for issue 6: the applicability of model system research.

PMID- 25067946
TI  - Guiding deployment of resistance in cereals using evolutionary principles.
AB  - Genetically controlled resistance provides plant breeders with an efficient means
      of controlling plant disease, but this approach has been constrained by practical
      difficulties associated with combining many resistance genes together and strong
      evolutionary responses from pathogen populations leading to subsequent resistance
      breakdown. However, continuing advances in molecular marker technologies are
      revolutionizing the ability to rapidly and reliably manipulate resistances of all
      types - major gene, adult plant and quantitative resistance loci singly or
      multiply into individual host lines. Here, we argue that these advances provide
      major opportunities to deliberately design deployment strategies in cereals that
      can take advantage of the evolutionary pressures faced by target pathogens.
      Different combinations of genes deployed either within single host individuals or
      between different individuals within or among crops, can be used to reduce the
      size of pathogen populations and generate patterns of disruptive selection. This
      will simultaneously limit immediate epidemic development and reduce the
      probability of subsequent evolutionary change in the pathogen for broader
      infectivity or increased aggressiveness. The same general principles are relevant
      to the control of noncereal diseases, but the most efficacious controls will vary
      reflecting the range of genetic options available and their fit with specific
      ecology and life-history combinations. 

PMID- 25067947
TI  - Loss of genetic integrity in wild lake trout populations following stocking:
      insights from an exhaustive study of 72 lakes from Quebec, Canada.
AB  - Stocking represents the most important management tool worldwide to increase and
      sustain commercial and recreational fisheries in a context of overexploitation.
      Genetic impacts of this practice have been investigated in many studies, which
      examined population and individual admixture, but few have investigated
      determinants of these processes. Here, we addressed these questions from the
      genotyping at 19 microsatellite loci of 3341 adult lake trout (Salvelinus
      namaycush) from 72 unstocked and stocked lakes. Results showed an increase in
      genetic diversity and a twofold decrease in the extent of genetic differentiation
      among stocked populations when compared to unstocked. Stocked populations were
      characterized by significant admixture at both population and individual levels.
      Moreover, levels of admixture in stocked populations were strongly correlated
      with stocking intensity and a threshold value of total homogenization between
      source and stocked populations was identified. Our results also suggest that
      under certain scenarios, the genetic impacts of stocking could be of short
      duration. Overall, our study emphasizes the important alteration of the genetic
      integrity of stocked populations and the need to better understand determinants
      of admixture to optimize stocking strategies and to conserve the genetic
      integrity of wild populations. 

PMID- 25067949
TI  - Detecting past changes of effective population size.
AB  - Understanding and predicting population abundance is a major challenge
      confronting scientists. Several genetic models have been developed using
      microsatellite markers to estimate the present and ancestral effective population
      sizes. However, to get an overview on the evolution of population requires that
      past fluctuation of population size be traceable. To address the question, we
      developed a new model estimating the past changes of effective population size
      from microsatellite by resolving coalescence theory and using approximate
      likelihoods in a Monte Carlo Markov Chain approach. The efficiency of the model
      and its sensitivity to gene flow and to assumptions on the mutational process
      were checked using simulated data and analysis. The model was found especially
      useful to provide evidence of transient changes of population size in the past.
      The times at which some past demographic events cannot be detected because they
      are too ancient and the risk that gene flow may suggest the false detection of a
      bottleneck are discussed considering the distribution of coalescence times. The
      method was applied on real data sets from several Atlantic salmon populations.
      The method called VarEff (Variation of Effective size) was implemented in the R
      package VarEff and is made available at https://qgsp.jouy.inra.fr and at
      http://cran.r-project.org/web/packages/VarEff. 

PMID- 25067948
TI  - Nuclear and mitochondrial genetic structure in the Eurasian beaver (Castor fiber)
      - implications for future reintroductions.
AB  - Many reintroduction projects for conservation fail, and there are a large number
      of factors that may contribute to failure. Genetic analysis can be used to help
      stack the odds of a reintroduction in favour of success, by conducting assessment
      of source populations to evaluate the possibility of inbreeding and outbreeding
      depression and by conducting postrelease monitoring. In this study, we use a
      panel of 306 SNP (single nucleotide polymorphism) markers and 487-489 base pairs
      of mitochondrial DNA control region sequence data to examine 321 individuals from
      possible source populations of the Eurasian beaver for a reintroduction to
      Scotland. We use this information to reassess the phylogenetic history of the
      Eurasian beavers, to examine the genetic legacy of past reintroductions on the
      Eurasian landmass and to assess the future power of the genetic markers to
      conduct ongoing monitoring via parentage analysis and individual identification.
      We demonstrate the capacity of medium density genetic data (hundreds of SNPs) to
      provide information suitable for applied conservation and discuss the difficulty
      of balancing the need for high genetic diversity against phylogenetic best fit
      when choosing source population(s) for reintroduction. 

PMID- 25067950
TI  - Relative contributions of neutral and non-neutral genetic differentiation to
      inform conservation of steelhead trout across highly variable landscapes.
AB  - Mounting evidence of climatic effects on riverine environments and adaptive
      responses of fishes have elicited growing conservation concerns. Measures to
      rectify population declines include assessment of local extinction risk,
      population ecology, viability, and genetic differentiation. While conservation
      planning has been largely informed by neutral genetic structure, there has been a
      dearth of critical information regarding the role of non-neutral or functional
      genetic variation. We evaluated genetic variation among steelhead trout of the
      Columbia River Basin, which supports diverse populations distributed among
      dynamic landscapes. We categorized 188 SNP loci as either putatively neutral or
      candidates for divergent selection (non-neutral) using a multitest association
      approach. Neutral variation distinguished lineages and defined broad-scale
      population structure consistent with previous studies, but fine-scale resolution
      was also detected at levels not previously observed. Within distinct coastal and
      inland lineages, we identified nine and 22 candidate loci commonly associated
      with precipitation or temperature variables and putatively under divergent
      selection. Observed patterns of non-neutral variation suggest overall climate is
      likely to shape local adaptation (e.g., potential rapid evolution) of steelhead
      trout in the Columbia River region. Broad geographic patterns of neutral and non
      neutral variation demonstrated here can be used to accommodate priorities for
      regional management and inform long-term conservation of this species. 

PMID- 25067953
TI  - Characterization of hydromechanical stress in aerated stirred tanks up to 40 m(3)
      scale by measurement of maximum stable drop size.
AB  - BACKGROUND: Turbulence intensity, or hydromechanical stress, is a parameter that
      influences a broad range of processes in the fields of chemical engineering and
      biotechnology. Fermentation processes are often characterized by high agitation
      and aeration intensity resulting in high gas void fractions of up to 20% in large
      scale reactors. Very little experimental data on hydromechanical stress for such
      operating conditions exists because of the problems associated with measuring
      hydromechanical stress under aeration and intense agitation. RESULTS: An indirect
      method to quantify hydromechanical stress for aerated operating conditions by the
      measurement of maximum stable drop size in a break-up controlled dispersion was
      applied to characterize hydromechanical stress in reactor scales of 50 L, 3 m(3)
      and 40 m(3) volume with a broad range of operating conditions and impeller
      geometries (Rushton turbines). Results for impellers within each scale for the
      ratio of maximum to specific energy dissipation rate phi based on measured values
      of maximum stable drop size for aerated operating conditions are qualitatively in
      agreement with results from literature correlations for unaerated operating
      conditions. Comparison of data in the different scales shows that there is a
      scale effect that results in higher values for phi in larger reactors. This
      behavior is not covered by the classic theory of turbulent drop dispersion but is
      in good agreement with the theory of turbulence intermittency. The data for all
      impeller configurations and all aeration rates for the three scales can be
      correlated within +/-20% when calculated values for phi based on the measured
      values for dmax are used to calculate the maximum local energy dissipation rate.
      A correlation of the data for all scales and all impeller configurations in the
      form phi = 2.3?(phiunaerated)(0.34)?(DR)(0.543) is suggested that successfully
      models the influence of scale and impeller geometry on phi for aerated operating
      conditions. CONCLUSIONS: The results show that besides the impeller geometry,
      also aeration and scale strongly influence hydromechanical stress. Incorporating
      these effects is beneficial for a successful scale up or scale down of this
      parameter. This can be done by applying the suggested correlation or by measuring
      hydromechanical stress with the experimental method used in this study.

PMID- 25067951
TI  - Misperceived invasion: the Lusitanian slug (Arion lusitanicus auct. non-Mabille
      or Arion vulgaris Moquin-Tandon 1855) is native to Central Europe.
AB  - The Lusitanian slug, presumed to be native to south-west Europe, was ranked among
      the 100 worst invading species in Central Europe. However, from the very
      beginning of its recognition in the presumed invasion area, there was little
      evidence that the species was actually anthropogenically introduced. We
      investigated the invasive status of the species by comparing specific predictions
      on the population genetic structure in the invasion area with the pattern
      actually found. In a DNA-taxonomy approach, the species could not be found in its
      presumed native range. Using statistical phylogeographic techniques on a
      mitochondrial (COI) and nuclear (ZF) marker and species distribution modelling,
      we could show that the species is with very high probability not an invasor, but
      native to Central Europe. The study underlines the value of statistical
      phylogeography in rigorously testing hypotheses on the dynamics of biological
      invasions. 

PMID- 25067954
TI  - Energy and nutrient intakes among Sri Lankan adults.
AB  - INTRODUCTION: The epidemic of nutrition related non-communicable diseases such as
      type 2 diabetes mellitus and obesity has reached to epidemic portion in the Sri
      Lanka. However, to date, detailed data on food consumption in the Sri Lankan
      population is limited. The aim of this study is to identify energy and major
      nutrient intake among Sri Lankan adults. METHODS: A nationally-representative
      sample of adults was selected using a multi-stage random cluster sampling
      technique. RESULTS: Data from 463 participants (166 Males, 297 Females) were
      analyzed. Total energy intake was significantly higher in males (1913 +/- 567
      kcal/d) than females (1514 +/- 458 kcal/d). However, there was no significant
      gender differences in the percentage of energy from carbohydrate (Male: 72.8 +/-
      6.4%, Female: 73.9 +/- 6.7%), fat (Male: 19.9 +/- 6.1%, Female: 18.5 +/- 5.7%)
      and proteins (Male: 10.6 +/- 2.1%, Female: 10.9 +/- 5.6%). CONCLUSION: The
      present study provides the first national estimates of energy and nutrient intake
      of the Sri Lankan adult population.

PMID- 25067955
TI  - Individual and social vulnerabilities upon acquiring tuberculosis: a literature
      systematic review.
AB  - Tuberculosis is a contagious infectious disease mainly caused by the bacteria
      Mycobacterium tuberculosis that still meets the priority criteria - high
      magnitude, transcendence and vulnerability - due to the threat it poses to public
      health. When taking into consideration the vulnerability conditions that favor
      the onset of the disease, this article aimed to investigate the implications
      originated from individual and social vulnerability conditions in which
      tuberculosis patients are inserted. Databases like MEDLINE, LILACS and SciELO
      were searched in Portuguese, Spanish and English using the descriptors
      tuberculosis and vulnerability, and 183 articles were found. After the selection
      criterion was applied, there were 22 publications left to be discussed. Some of
      the aspects that characterize the vulnerability to tuberculosis are: low-income
      and low-education families, age, poor living conditions, chemical dependency, pre
      existing conditions/aggravations like diabetes mellitus and malnutrition,
      indigenous communities, variables related to health professionals, intense border
      crossings and migration, difficulty in accessing information and health services
      and lack of knowledge on tuberculosis. Much as such aspects are present and favor
      the onset of the disease, several reports show high incidence rates of
      tuberculosis in low vulnerability places, suggesting that some factors related to
      the disease are still unclear. In conclusion, health promotion is important in
      order to disfavor such conditions or factors of vulnerability to tuberculosis,
      making them a primary target in the public health planning process and disease
      control. 

PMID- 25067956
TI  - A BRCA1-mutation associated DNA methylation signature in blood cells predicts
      sporadic breast cancer incidence and survival.
AB  - BACKGROUND: BRCA1 mutation carriers have an 85% risk of developing breast cancer
      but the risk of developing non-hereditary breast cancer is difficult to assess.
      Our objective is to test whether a DNA methylation (DNAme) signature derived from
      BRCA1 mutation carriers is able to predict non-hereditary breast cancer. METHODS:
      In a case/control setting (72 BRCA1 mutation carriers and 72 BRCA1/2 wild type
      controls) blood cell DNA samples were profiled on the Illumina 27 k methylation
      array. Using the Elastic Net classification algorithm, a BRCA1-mutation DNAme
      signature was derived and tested in two cohorts: (1) The NSHD (19 breast cancers
      developed within 12 years after sample donation and 77 controls) and (2) the
      UKCTOCS trial (119 oestrogen receptor positive breast cancers developed within 5
      years after sample donation and 122 controls). RESULTS: We found that our blood
      based BRCA1-mutation DNAme signature applied to blood cell DNA from women in the
      NSHD resulted in a receiver operating characteristics (ROC) area under the curve
      (AUC) of 0.65 (95% CI 0.51 to 0.78, P = 0.02) which did not validate in buccal
      cells from the same individuals. Applying the signature in blood DNA from UKCTOCS
      volunteers resulted in AUC of 0.57 (95% CI 0.50 to 0.64; P = 0.03) and is
      independent of family history or any other known risk factors. Importantly the
      BRCA1-mutation DNAme signature was able to predict breast cancer mortality (AUC =
      0.67; 95% CI 0.51 to 0.83; P = 0.02). We also found that the 1,074 CpGs which are
      hypermethylated in BRCA1 mutation carriers are significantly enriched for stem
      cell polycomb group target genes (P <10(-20)). CONCLUSIONS: A DNAme signature
      derived from BRCA1 carriers is able to predict breast cancer risk and death years
      in advance of diagnosis. Future studies may need to focus on DNAme profiles in
      epithelial cells in order to reach the AUC thresholds required of preventative
      measures or early detection strategies.

PMID- 25067958
TI  - Setting the course for apoAII: a port in sight?
AB  - ApoAII, the second most abundant protein of the human plasma HDLs, was discovered
      nearly 50 years ago. Over the subsequent years, nearly 2000 studies -
      epidemiological, cell-based, biochemical, mouse and human - have attempted to
      unravel its role in human lipid metabolism. On the basis of these studies, apoAII
      has been described as an activator and inhibitor of various plasma activities,
      and as both pro- and anti-atherogenic. Here, we summarize the studies of apoAII,
      use the preponderance of evidence to propose that the apoAII compass can be reset
      towards an antiatherogenic course, and suggest ways to stay the course.

PMID- 25067959
TI  - Advancing Research in School Mental Health: Introduction of a Special Issue on
      Key Issues in Research.

PMID- 25067957
TI  - Targeting sirtuins for the treatment of diabetes.
AB  - Sirtuins are a class of NAD+-dependent deacetylases, such as deacetylases, that
      have a wide array of biological functions. Recent studies have suggested that
      reduced sirtuin action is correlated with Type 2 diabetes. Both overnutrition and
      aging, which are two major risk factors for diabetes, lead to decreased sirtuin
      function and result in abnormal glucose and lipid metabolism. Therefore,
      restoring normal levels of sirtuin action in Type 2 diabetes may be a promising
      method of treating diabetes. This article reviews the biological functions of
      three of the seven mammalian sirtuins - SIRT1, SIRT3 and SIRT6 - that have
      demonstrated prominent metabolic roles and early potential for drug targeting.
      Clinical trials investigating the use of sirtuin activators for treating diabetes
      are already underway and show promise as alternatives to current diabetes
      therapies. Thus, further research into sirtuin activators is warranted and may
      lead to a new class of safe, effective diabetes treatments.

PMID- 25067960
TI  - Are Blacks and Hispanics Disproportionately Incarcerated Relative to Their
      Arrests? Racial and Ethnic Disproportionality Between Arrest and Incarceration.
AB  - Do large racial and ethnic disparities in prison populations reflect systematic
      racial and policy discrimination in the criminal justice system, or do they
      reflect disproportionate involvement of blacks and Hispanics in "serious" or
      street crime? Our investigation of this question keys off the approach initiated
      by Alfred Blumstein is his pioneering studies on the topic. While yielding
      important findings, there are, however, substantial gaps in the empirical
      literature on the racial disproportionality issue. We attempt to fill those gaps
      by (1) using both data on prison admission as well as in-stock prison
      populations, (2) presenting more recent racially and ethnically disaggregated
      arrest and incarceration data from Pennsylvania for 2003-2007, and (3) including
      Hispanic offenders in our racial and ethnic disproportionality comparisons. Our
      results indicate, first, that the representation of blacks, whites, and Hispanics
      among offenders admitted to state prison and in the prison population corresponds
      closely to their representation in arrest statistics. Second, using arrests as a
      marker of violent offending, the overrepresentation of blacks among offenders
      admitted to state prisons occurs because they commit a disproportionate number of
      frequently imprisoned (i.e., violent) crimes. Third, for those offenses where
      there is a within-race difference between arrest and incarceration
      representation, Hispanics experience the greatest disadvantage. Fourth, failing
      to account for Hispanics in white and black estimates tends to inflate white
      proportions and deflate black proportions of arrests, admissions, and prison
      population estimates, masking the "true" black and white racial
      disproportionality. We conclude that while there is a need for continued concern
      with possible racial discrimination in justice system processing, this concern
      should not distract attention from what arguably is the more important matter
      ameliorating the social environmental conditions that foster disproportionate
      minority (especially black) involvement in violent crime.

PMID- 25067961
TI  - Mindfulness-Based Cognitive Approach for Seniors (MBCAS): Program Development and
      Implementation.
AB  - A number of cognitive interventions have been developed to enhance cognitive
      functioning in the growing population of the elderly. We describe the Mindfulness
      Based Cognitive Approach for Seniors (MBCAS), a new training program designed
      especially for seniors. It was conceived in the context of self-development for
      seniors who wish to enhance their relationship with their inner and outer selves
      in order to navigate their aging process more easily and fluently. Physical and
      psychosocial problems related to aging, as well as some temporal issues, were
      taken into account in developing this program. Unlike clinically oriented
      mindfulness-based programs, which are generally delivered during an 8-week
      period, the MBCAS training program is presented over a period of 8 months. The
      main objectives of this program are to teach seniors to observe current
      experiences with nonjudgmental awareness, to identify automatic behaviors or
      reactions to current experiences that are potentially nonadaptive, and to enhance
      and reinforce positive coping with typical difficulties that they face in their
      daily lives. Details of the program development and initial implementation are
      presented, with suggestions for evaluating the program's effectiveness.

PMID- 25067962
TI  - Effect of Body Composition Methodology on Heritability Estimation of Body
      Fatness.
AB  - Heritability estimates of human body fatness vary widely and the contribution of
      body composition methodology to this variability is unknown. The effect of body
      composition methodology on estimations of genetic and environmental contributions
      to body fatness variation was examined in 78 adult male and female monozygotic
      twin pairs reared apart or together. Body composition was assessed by six methods
      - body mass index (BMI), dual energy x-ray absorptiometry (DXA), underwater
      weighing (UWW), total body water (TBW), bioelectric impedance (BIA), and skinfold
      thickness. Body fatness was expressed as percent body fat, fat mass, and fat
      mass/height2 to assess the effect of body fatness expression on heritability
      estimates. Model-fitting multivariate analyses were used to assess the genetic
      and environmental components of variance. Mean BMI was 24.5 kg/m2 (range of 17.8
      43.4 kg/m2). There was a significant effect of body composition methodology
      (p<0.001) on heritability estimates, with UWW giving the highest estimate (69%)
      and BIA giving the lowest estimate (47%) for fat mass/height2. Expression of body
      fatness as percent body fat resulted in significantly higher heritability
      estimates (on average 10.3% higher) compared to expression as fat mass/height2
      (p=0.015). DXA and TBW methods expressing body fatness as fat mass/height2 gave
      the least biased heritability assessments, based on the small contribution of
      specific genetic factors to their genetic variance. A model combining DXA and TBW
      methods resulted in a relatively low FM/ht2 heritability estimate of 60%, and
      significant contributions of common and unique environmental factors (22% and
      18%, respectively). The body fatness heritability estimate of 60% indicates a
      smaller contribution of genetic variance to total variance than many previous
      studies using less powerful research designs have indicated. The results also
      highlight the importance of environmental factors and possibly genotype by
      environmental interactions in the etiology of weight gain and the obesity
      epidemic.

PMID- 25067963
TI  - Genetic and Environmental Influences on Eating Behavior - A Study of Twin Pairs
      Reared Apart or Reared Together.
AB  - This study examined the relative influence of genetic versus environmental
      factors on specific aspects of eating behavior. Adult monozygotic twins (22 pairs
      and 3 singleton reared apart, 38 pairs and 9 singleton reared together, age 18-76
      years, BMI 17-43 kg/m2) completed the Three Factor Eating Questionnaire. Genetic
      and environmental variance components were determined for the three eating
      behavior constructs and their subscales using model-fitting univariate and
      multivariate analyses. Unique environmental factors had a substantial influence
      on all eating behavior variables (explaining 45-71% of variance), and most
      strongly influenced external locus for hunger and strategic dieting behavior of
      restraint (explaining 71% and 69% of variance, respectively). Genetic factors had
      a statistically significant influence on only 4 variables: restraint, emotional
      susceptibility to disinhibition, situational susceptibility to disinhibition, and
      internal locus for hunger (heritabilities were 52%, 55%, 38% and 50%,
      respectively). Common environmental factors did not statistically significantly
      influence any variable assessed in this study. In addition, multivariate analyses
      showed that disinhibition and hunger share a common influence, while restraint
      appears to be a distinct construct. These findings suggest that the majority of
      variation in eating behavior variables is associated with unique environmental
      factors, and highlights the importance of the environment in facilitating
      specific eating behaviors that may promote excess weight gain.

PMID- 25067964
TI  - Adult-Onset Still's Disease Associated with Thyroid Dysfunction: Case Report and
      Review of the Literature.
AB  - To our knowledge, the possible unveiled interaction between adult-onset Still's
      disease (AOSD) with autoimmune thyroid disease (AITD) has never been reported
      although it is well established that systemic autoimmune disease may usually
      occur in relation to AITD. As increasingly clear links of AITD with other
      autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA), and primary Sjogren's syndrome (pSS) have been reported, and the
      incidence of AOSD concurrent AITD draws our attention rapidly. In this study, we
      searched relevant literatures published in the past 30 years to explore that
      condition. 

PMID- 25067965
TI  - Tendon-holding capacities of two newly designed implants for tendon repair: an
      experimental study on the flexor digitorum profundus tendon of sheep.
AB  - BACKGROUND: Two main factors determine the strength of tendon repair; the tensile
      strength of material and the gripping capacity of a suture configuration.
      Different repair techniques and suture materials were developed to increase the
      strength of repairs but none of techniques and suture materials seem to provide
      enough tensile strength with safety margins for early active mobilization. In
      order to overcome this problem tendon suturing implants are being developed. We
      designed two different suturing implants. The aim of this study was to measure
      tendon-holding capacities of these implants biomechanically and to compare them
      with frequently used suture techniques. MATERIALS AND METHODS: In this study we
      used 64 sheep flexor digitorum profundus tendons. Four study groups were formed
      and each group had 16 tendons. We applied model 1 and model 2 implant to the
      first 2 groups and Bunnell and locking-loop techniques to the 3rd and 4th groups
      respectively by using 5 Ticron sutures. RESULTS: In 13 tendons in group 1 and 15
      tendons in group 2 and in all tendons in group 3 and 4, implants and sutures
      pulled out of the tendon in longitudinal axis at the point of maximum load. The
      mean tensile strengths were the largest in group 1 and smallest in group 3.
      CONCLUSION: In conclusion, the new stainless steel tendon suturing implants
      applied from outside the tendons using steel wires enable a biomechanically
      stronger repair with less tendon trauma when compared to previously developed
      tendon repair implants and the traditional suturing techniques.

PMID- 25067966
TI  - Controversies in the management of soft tissue injuries.

PMID- 25067967
TI  - Negative pressure wound therapy - a review of its uses in orthopaedic trauma.
AB  - The use of Negative Pressure Wound Therapy (NPWT) for complex and large wounds
      has increased in popularity over the past decade. Modern NPWT systems consisting
      of an open pore foam sponge, adhesive dressing and a vacuum pump producing
      negative pressure have been used as an adjunct to surgical debridement to treat
      tissue defects around open fractures and chronic, contaminated wounds. Other uses
      include supporting skin grafts and protecting wounds at risk of breaking down.
      This review outlines the current and emerging indications for negative pressure
      wound therapy in Orthopaedic trauma and the existing preclinical and clinical
      evidence base for its use. 

PMID- 25067968
TI  - A review of management options for proximal humeral fractures.
AB  - Proximal humeral fractures are common and although the majority can be managed
      non-operatively, the optimal treatment of displaced or complex fractures remains
      controversial. Non-operative treatment is typically selected for minimally
      displaced fractures where union rates are high and good or excellent outcomes can
      be expected in approximately 80% of cases. The aims of surgical fixation are to
      restore articular surface congruency, alignment and the relationship between the
      tuberosities and the humeral head. Hemiarthroplasty provides patients with
      reliable pain relief and its indications include fracture dislocations, humeral
      head splitting fractures and some three- and four- part fractures. The key areas
      of surgical technique that influence functional outcome include correctly
      restoring the humeral height, humeral version and tuberosity position. Function,
      however, is poor if the tuberosities either fail to unite or mal-unite. The
      interest in reverse shoulder arthroplasty as an alternative option has therefore
      recently increased, particularly in older patients with poor bone quality and
      tuberosity comminution. The evidence supporting this, however, is currently
      limited to multiple case series with higher level studies currently underway. 

PMID- 25067969
TI  - Bite injuries to the hand: microbiology, virology and management.
AB  - Bites to the human hand, be it from a pet, a stray animal or even a fellow human,
      may often have dire consequences for the person suffering the insult. Bites by
      mammals are a common problem and they account for up to 1% of all visits to
      hospital emergency rooms, in the UK. Clenched fist injuries to the mouth ('fight
      bite') are notorious for being the worst human bites. Bite injuries of the hand
      and their related infections must be monitored vigilantly and managed
      proactively, by experts in this field of surgery. In this review article we
      discuss the associated microbiology and virology of these injuries as well as
      their management. 

PMID- 25067970
TI  - Current concepts in acute knee dislocation: the missed diagnosis?
AB  - Traumatic knee dislocation is a serious and potentially limb threatening injury
      that can be easily missed if meticulous history and examination have not been
      employed. Neurovascular injuries are common in this condition, and due diligence
      should be given to their thorough evaluation at time of secondary survey so as to
      avoid complications such as ischaemia, compartment syndrome and eventual
      amputation. There is growing evidence in the literature that morbid obesity is
      associated with low energy knee dislocation, therefore this should be considered
      when assessing this cohort of patients presenting with an acute knee injury.
      Early operative intervention especially with multi ligaments involvement is the
      preferable strategy in the management of this acute injury. Controversy exists
      whether to reconstruct or repair damaged structures, and whether to adopt a one
      stage or two stage reconstruction of the cruciate ligaments. Early rehabilitation
      is important and essential to achieve satisfactory outcomes. This article is an
      evidence-based overview of this rare but devastating injury. 

PMID- 25067971
TI  - The evidence-based principles of negative pressure wound therapy in trauma &
      orthopedics.
AB  - Negative pressure wound therapy is a popular treatment for the management of both
      acute and chronic wounds. Its use in trauma and orthopedics is diverse and
      includes the acute traumatic setting as well as chronic troublesome wounds
      associated with pressure sores and diabetic foot surgery. Efforts have been made
      to provide an evidence base to guide its use however this has been limited by a
      lack of good quality evidence. The following review article explores the
      available evidence and describes future developments for its use in trauma and
      orthopaedic practice. 

PMID- 25067972
TI  - Controversies in the management of open fractures.
AB  - Open fractures are a common problem encountered by orthopaedic surgeons and
      comprise a broad spectrum of trauma. Management is guided by principle-based
      steps aimed at reducing the risk of gas gangrene or suppurative infections,
      whilst maintaining viability in a favourable soft tissue environment to reduce
      the risk of delayed or non-union of bone. Aspects of these principles, however,
      create discussion around several areas of controversy. The specific antimicrobial
      regimen and its duration are questions that have been evaluated for decades. Like
      the ever-evolving nature of the bacterial pathogens, the answer to this is
      dynamic and changing. The "six-hour rule" is a hotly debated topic with fervent
      perseverance of this dogma despite a gross lack of support from the literature.
      The most appropriate soft tissue management approach for open fractures -
      immediate definitive soft tissue closure versus leaving wounds open for delayed
      closure or definitive management - is also an area of debate. Exploration of
      these controversies and consideration for the historical context of the
      supporting literature furthers our understanding of the critical elements. 

PMID- 25067973
TI  - The pathophysiology, diagnosis and current management of acute compartment
      syndrome.
AB  - Acute compartment syndrome (ACS) is a surgical emergency warranting prompt
      evaluation and treatment. It can occur with any elevation in interstitial
      pressure in a closed osseo-fascial compartment. Resultant ischaemic damage may be
      irreversible within six hours and can result in long-term morbidity and even
      death. The diagnosis is largely clinical with the classical description of 'pain
      out of proportion to the injury'. Compartment pressure monitors can be a helpful
      adjunct where the diagnosis is in doubt. Initial treatment is with the removal of
      any constricting dressings or casts, avoiding hypotension and optimizing tissue
      perfusion by keeping the limb at heart level. If symptoms persist, definitive
      treatment is necessary with timely surgical decompression of all the involved
      compartments. This article reviews the pathophysiology, diagnosis and current
      management of ACS. 

PMID- 25067974
TI  - Mammalian bite injuries to the hand and their management.
AB  - Bite wounds are a common form of hand injury with the potential to lead to severe
      local and systemic sequelae and permanent functional impairment. Mammalian bite
      wounds may be caused by a variety of animal class and species; injuries resulting
      from dogs, cats and humans are the most widely discussed and reported in the
      literature. Bite wounds may be contaminated with aggressive pathogens and the
      anatomical vulnerability of structures within the hand means that without early
      recognition and treatment with irrigation and antibiotics, alongside a low index
      of suspicion for deep structural involvement requiring formal surgical
      exploration and washout, the consequences of such injuries can be disastrous. We
      review the literature and discuss the epidemiology, pathophysiology and
      microbiology relating to these injuries, as well as clinical aspects including
      signs, symptoms, and management. 

PMID- 25067975
TI  - Peripheral nerve injury: principles for repair and regeneration.
AB  - Peripheral Nerve Injuries are one of the most common causes of hand dysfunction
      caused by upper limb trauma but still current management has remained suboptimal.
      This review aims to explain the traditional view of pathophysiology of nerve
      repair and also describe why surgical management is still inadequate in using the
      new biological research that has documented the changes that occur after the
      nerve injury, which, could cause suboptimal clinical outcomes. Subsequently
      presentation and diagnosis will be described for peripheral nerve injuries. When
      traditional surgical repair using end-to-end anastomosis is not adequate nerve
      conduits are required with the gold standard being the autologous nerve. Due to
      associated donor site morbidity and poor functional outcome documented with
      autologous nerve repair several new advancements for alternatives to bridge the
      gap are being investigated. We will summarise the new and future advancements of
      non-biological and biological replacements as well as gene therapy, which are
      being considered as the alternatives for peripheral nerve repair. 

PMID- 25067976
TI  - Knee Osteochondritis Dissecans Treated by the AO Hook Fixation System: A Four
      Year Follow-Up of an Alternative Technique.
AB  - Surgical fixation is recommended for stable osteochondritis dissecans (OCD)
      lesions that have failed nonoperative management and for all unstable lesions. In
      this study we set out to describe and evaluate an alternative method of surgical
      fixation for such lesions. Five knees with unstable OCD lesions in four male
      adolescent patients with open physes were treated with the AO Hook Fixation
      System. The outcome was evaluated both clinically and with three separate outcome
      systems (IKDC 2000, KOOS, Lysholm) at one and a mean four year follow-up. We
      demonstrated excellent clinical results in all patients. At four years, all
      scoring systems demonstrated statistically significant improvement when compared
      to the preoperative status. Our study suggests that the AO Hook Fixation System
      is an alternative method of surgical intervention with comparable medium term
      results with other existing modes of fixation and the added biomechanical
      advantage of the absence of distracting forces during hardware removal. 

PMID- 25067977
TI  - State of the art regarding the management of multiligamentous injuries of the
      knee.
AB  - Multiligamentous knee injuries are rare but serious injuries that can threaten
      limb viability. As such, they require careful management to give patients the
      best chance of immediate and ultimate functional recovery. However, as these
      injuries are rare, there is paucity in prospective comparative studies large
      enough to provide high level evidence for best practice. This lack of
      comprehensive and convincing evidence has made the management of multiligamentous
      knee injuries an area of active debate and controversy. The debate on whether
      surgical management leads to better outcomes than non-operative management, the
      optimal timing of surgery after injury and whether repair is better than
      reconstruction is still ongoing. Using the Oxford Levels of Evidence, this review
      summarises the latest high level evidence to provide answers to these issues.
      Recommendations for practice have also been offered and assigned a grade using a
      published scale. 

PMID- 25067978
TI  - Laser cyclophotocoagulation enhances the regulative capacity of retinal vessels
      in glaucoma.
AB  - PURPOSE: To determine the effects of laser surgical IOP reduction by means of
      transscleral cyclophotocoagulation (CPC) on retinal blood flow parameters in
      glaucoma patients using Dynamic Vessel Analysis (DVA). MATERIALS AND METHODOLOGY:
      26 patients (average age: 70 years) with a long history of primary open angle
      glaucoma underwent CPC. The effect on the reactive capacity of retinal vessels
      was assessed before and 6-8 weeks after CPC by means of the Dynamic Vessel
      Analyzer (DVA) using flicker light provocation. RESULTS: In our group of POAG
      patients, IOP was significantly reduced about approximately 20% by CPC while
      systemic blood pressure and heart rate were not changed. The most obvious
      differences between the pre- and postoperative DVA measurements could be observed
      in the maximal dilation of the retinal arteries which increased from 0.75 % (+/-
      0.6) to 3.17 % (+/- 0.5) with an average increase of 2.4 % (p<0.01). In addition,
      the ability of the arteries for constriction improved significantly (p<0.05)
      while the dynamic responses of the veins and the initial baseline values (MU) of
      the vessel diameters did not change. CONCLUSIONS: Our results of DVA measurements
      after an IOP-lowering laser surgical intervention (CPC) reveal a significant
      recovery of the regulative capacity of retinal arteries in glaucoma patients that
      has up to now neither been properly documented nor appreciated. Future studies
      with long-term follow-up must determine the clinical importance of these findings
      for the treatment of glaucoma patients.

PMID- 25067979
TI  - Classical pathology of sympathetic ophthalmia presented in a unique case.
AB  - The ocular pathology of sympathetic ophthalmia is demonstrated in a 10 year-old
      boy who sustained a penetrating left globe injury and subsequently developed
      sympathetic ophthalmia in the right eye two months later. Two and a half weeks
      following extensive surgical repair of the left ruptured globe, he developed
      endophthalmitis and was treated with oral and topical fortified antibiotics. One
      month after the initial injury, a progressive corneal ulcer of the left eye led
      to perforation and the need for emergent corneal transplantation. The surgical
      specimen revealed fungus, Scedosporium dehoogii. The boy received systemic and
      topical anti-fungal therapy. Two months following the penetrating globe injury of
      the left eye, a granulomatous uveitis developed in the right eye. Sympathetic
      ophthalmia was suspected and the patient began treatment with topical and oral
      corticosteroids. Given the concern of vision loss secondary to sympathetic
      ophthalmia in the right eye, as well as poor vision and hypotony in the injured
      eye, the left eye was enucleated. Microscopically, granulomatous inflammation
      with giant cells was noted within a cyclitic membrane which filled the anterior
      and posterior chamber of the left globe. Other classic features including Dalen
      Fuchs nodules were identified. Small, choroidal, ill-defined granulomas and
      relative sparing of the choriocapillaris were present. Molecular analysis did not
      identify evidence of remaining fungal infection. The pathology findings were
      consistent with previously described features of sympathetic ophthalmia. The
      present case is unique in that co-existing fungal infection may have potentiated
      the risk for developing sympathetic ophthalmia in the fellow eye. 

PMID- 25067980
TI  - Development of 14 microsatellite markers in the Queensland koala (Phascolarctos
      cinereus adustus) using next generation sequencing technology.
AB  - We report the development of 14 new microsatellite markers in the Queensland
      koala (Phascolarctos cinereus adustus). Ten unrelated Queensland koala
      individuals from the San Diego Zoo, USA, were genotyped. The number of alleles
      per locus ranged from 2 to 7, with an average of 5.14 alleles per locus. Across
      all loci, the average observed and expected heterozygosity values were both 0.69.
      These polymorphic microsatellite loci will be useful for genetic studies relevant
      to the conservation of the koala, a species listed as vulnerable.

PMID- 25067981
TI  - A Comparison of Fibromyalgia Symptoms in Patients with Healthy versus Depressive,
      Low and Reactive Affect Balance Styles.
AB  - BACKGROUND AND AIMS: Affect balance reflects relative levels of negative affect
      (NA) and positive affect (PA) and includes four styles: Healthy (low NA/high PA),
      Depressive (high NA/low PA), Reactive (high NA/high PA) and Low (low NA/low PA).
      These affect balance styles may have important associations with clinical
      outcomes in patients with fibromyalgia. Herein, we evaluated the severity of core
      fibromyalgia symptom domains as described by the Outcomes Research in
      Rheumatology-Fibromyalgia working group in the context of the four affect balance
      styles. METHODS: Data from735 patients with fibromyalgia who completed the Brief
      Pain Inventory, Multidimensional Fatigue Inventory, Profile of Mood States,
      Medical Outcomes Sleep Scale, Multiple Ability Self-Report Questionnaire,
      Fibromyalgia Impact Questionnaire-Revised, Medical Outcomes Study Short Form-36,
      and Positive and Negative Affect Schedule were included in this analysis.
      RESULTS: The majority (51.8%) of patients in our sample had a Depressive affect
      balance style; compared to patients with a Healthy affect balance style, they
      scored significantly worse in all fibromyalgia symptom domains including pain,
      fatigue, sleep disturbance, dyscognition, depression, anxiety, stiffness, and
      functional status (P = <.001 - .004). Overall, patients with a Healthy affect
      balance style had the lowest level of symptoms, while symptom levels of those
      with Reactive and Low affect balance styles were distributed in between those of
      the Depressive and Healthy groups. CONCLUSIONS AND IMPLICATIONS: The results of
      our cross-sectional study suggest that having a Healthy affect balance style is
      associated with better physical and psychological symptom profiles in
      fibromyalgia. Futures studies evaluating these associations longitudinally could
      provide rationale for evaluating the effect of psychological interventions on
      affect balance and clinical outcomes in fibromyalgia.

PMID- 25067982
TI  - Effect of probenecid on pharmacokinetics and tolerability of olmesartan in
      healthy chinese volunteers.
AB  - BACKGROUND: Olmesartan is an angiotensin II receptor antagonist and is effective
      and well tolerated in the treatment of arterial hypertension. Probenecid is a
      well-established hypouricemic agent for the treatment of hyperuricemia and gout.
      OBJECTIVE: The goal of this study was to examine the impact of coadministration
      of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in
      healthy volunteers. METHODS: In a randomized, open-label, 2-way crossover study,
      12 volunteers received 2 oral treatments (olmesartan alone or olmesartan plus
      probenecid) separated by 4 days. Blood samples were obtained for a 48-hour
      pharmacokinetic evaluation after drug administration. Tolerability was assessed
      by monitoring vital signs and laboratory tests before and after administration of
      the study drug. RESULTS: Pharmacokinetic parameters were evaluated in 6 male and
      6 female healthy volunteers (mean age, 22 [range, 20-25] years]; weight, 56.0
      [range, 51.0-60.0] kg). Probenecid coadministration increased olmesartan Css-av,
      AUC0->infinity, and AUC0-48 by 40%, 50%, and 50%, respectively (P = 0.018, 0.000,
      0.000, respectively), but there was no statistical significance for Tmax, t1/2,
      Css-max, and Css-min between olmesartan plus probenecid and olmesartan alone (P =
      0.697, 0.053, 0.521, and 0.734, respectively). No serious adverse event (AE) was
      reported during the study. The proportion of volunteers with AEs in the
      olmesartan plus probenecid period (5 of 12 [42%]) was higher than that in the
      olmesartan-alone period (1 of 12 [8%]). All of the AEs during the olmesartan plus
      probenecid period were abnormal routine urine test results. The AE in olmesartan
      alone period was dizziness. All AEs were classified as mild and considered to be
      at least possibly related to treatment. All volunteers recovered from the AEs by
      2 weeks after the end of the study. CONCLUSIONS: Probenecid increases the
      exposure speed of olmesartan by increasing the AUC0-48, AUC0->infinity, and Css
      av. The combined treatment of olmesartan medoxomil with probenecid may increase
      the occurrence of genitourinary side effects. ClinicalTrials.gov identifier:
      NCT01907373.

PMID- 25067983
TI  - Best pharmaceuticals for children: how far have we come?

PMID- 25067984
TI  - Tympanic, infrared skin, and temporal artery scan thermometers compared with
      rectal measurement in children: a real-life assessment.
AB  - INTRODUCTION: Body temperature measurement in children is of clinical relevance.
      Although rectal measurement is the gold standard, less invasive tools have become
      available. We aimed to describe the accuracy of tympanic, infrared skin, or
      temporal artery scan thermometers compared with rectal measurement to reflect
      core temperature. METHODS: Rectal (Filac 3000; Covidien, Mechelen, Belgium),
      tympanic (AccuSystem Genius2 Typmanic Infrared Ear Thermometer, Covidien,
      Mechelen, Belgium), temporal artery scan (Exergen, Exergen Corp, Watertown,
      Massachusetts), and infrared (ThermoFlash Contactless Medical Electronic
      Thermometer, Visiomedlab, Paris, France) body temperature measurements were
      randomly performed and readings were collected once. Temperature readings were
      described as median and range, and observations were compared with rectal
      temperature readings (using Wilcoxon, Bland-Altman, sensitivity, and specificity
      tests). The child's comfort was assessed by the child, parent, and nurse (using
      Likert scales) and ease of use was assessed by nurses (using visual analog
      scale). RESULTS: Based on observations in 294 (median age = 3.2 years, range =
      0.02-17 years) children, the mean difference was 0.49 degrees C (tympanic scan; P
      < 0.0001), 0.34 degrees C (infrared skin scan; P < 0.0001), and 0 degrees C
      (temporal artery scan; P = 0.9288), respectively, when compared with rectal
      temperature readings. Based on visual inspection of Bland-Altman plots, all tools
      overestimated the temperature at lower body temperature and underestimated the
      temperature at higher body temperature, resulting in a sensitivity of 22% to 41%
      and a specificity of 98% to 100% for rectal temperatures above 38 degrees C. The
      Likert scale scores and the visual analog scale scores for rectal measurement
      were only slightly higher when compared with the other methods. CONCLUSIONS: All
      noninvasive techniques underperformed compared with rectal measurement. The
      temporal artery scan deviations were smallest, but all noninvasive techniques
      overestimate lower temperatures and underestimate higher temperatures compared
      with rectal measurement. In our hands, temporal artery scan measurement seems to
      be second best, but not yet ideal.

PMID- 25067986
TI  - Effect of xanthone derivatives on animal models of depression.
AB  - BACKGROUND: Extracts of the plant Hypericum perforatum L. have been traditionally
      used in folk medicine for the treatment of depressive disorders. Xanthone, a
      component of Hypericum perforatum L., has been shown to be effective in animal
      models of depression. OBJECTIVE: We investigated if 2 xanthone derivatives (1101
      and 1105) were as effective as venlafaxine, which is a serotonin-norepinephrine
      reuptake inhibitor and was used as a positive control, in animal models of
      depression. METHODS: A series of derivatives from xanthone were designed and
      synthesized. After preliminary experiments, 2 xanthone derivatives (1101 and
      1105) were considered to be effective in our mouse depression model. To further
      determine their effects on depression, classical behavioral despair animal models
      (forced swim and tail suspension tests) were used to assess the efficacies of
      these derivatives, whereas venlafaxine hydrochloride was used as a positive
      control. Oral acute toxicity studies were used to determine if the derivatives
      were toxic in mice. RESULTS: The oral acute toxicity studies of 2 xanthone
      derivatives (1101 and 1105) did not show any toxic effect until the dose at 1000
      mg/kg body weight, and xanthone derivatives 1101 and 1105 resulted in a
      significant decrease of the immobility period (in seconds) compared with the
      untreated control group during the forced swim test with rats (dose = 12 mg/kg; P
      < 0.05) and mice (dose = 25 mg/kg; P < 0.001). At lower doses, derivatives 1101
      and 1105 also decreased the immobility period of rats and mice during the forced
      swim test but significant differences were only found in mice compared with the
      untreated control group (P < 0.05). No difference was found between the groups
      treated with xanthone derivatives and the positive control group during the
      swimming period in both mice (dose = 25 mg/kg) and rats (dose = 12 mg/kg) (P >
      0.05). In the tail suspension test, derivatives 1101 and 1105 produced marked
      effects with regard to the motion of mice (P < 0.01 or 0.001, respectively) and
      the derivatives were also noted to have some effects on rats at a dose of 12
      mg/kg (P < 0.05). Compared with the positive venlafaxine control group, no
      differences were found between those treated with either derivative 1101 or
      derivative 1105 and venlafaxine (P > 0.05). CONCLUSIONS: Within certain dose
      ranges, xanthone derivatives 1101 and 1105 have similar effects to venlafaxine
      hydrochloride in the treatment of depression as suggested by behavioral despair
      animal models using rats and mice.

PMID- 25067985
TI  - Effects of cactus fiber on the excretion of dietary fat in healthy subjects: a
      double blind, randomized, placebo-controlled, crossover clinical investigation.
AB  - BACKGROUND: Cactus (Opuntia ficus-indica) fiber was shown to promote weight loss
      in a 3-month clinical investigation. As demonstrated by in vitro studies, cactus
      fiber binds to dietary fat and its use results in reduced absorption, which in
      turn leads to reduced energy absorption and ultimately the reduction of body
      weight. OBJECTIVE: The objective of our study was to elucidate the dietary fat
      binding capacity of cactus fiber through determination of fecal fat excretion in
      healthy volunteers. SUBJECTS AND METHODS: This clinical investigation was
      performed as a double-blind, randomized, placebo-controlled, crossover study in
      healthy subjects for a period of approximately 45 days. Twenty healthy volunteer
      subjects were randomized to receive cactus fiber or placebo, 2 tablets thrice
      daily with main meals. All subjects were provided with meals during the study
      period (except washout) according to a standardized meal plan, with 35% of daily
      energy need coming from fat. Two 24-hour feces samples were collected during both
      the baseline and treatment periods for analysis of the fat content. RESULTS:
      Cactus fiber showed an increased fecal fat excretion compared with placebo (mean
      [SD] = 15.79% [5.79%] vs 4.56% [3.09%]; P < 0.001). No adverse events were
      reported throughout the study period. CONCLUSIONS: Cactus fiber has been shown to
      significantly promote fecal fat excretion in healthy adults. The results of our
      study support the hypothesis that cactus fiber helps in reducing body weight by
      binding to dietary fat and increasing its excretion, thus reducing dietary fat
      available for absorption. ClinicalTrials.gov identifier: NCT01590667.

PMID- 25067987
TI  - The effect of hypertonic saline on mRNA of proinflammatory cytokines in
      lipopolysaccharide-stimulated polymorphonuclear cells.
AB  - BACKGROUND: Hypertonic saline is often used to resuscitate patients experiencing
      shock. In such conditions, polymorphonuclear cells and Toll-like receptors (TLRs)
      form an essential part of early induced innate immunity. OBJECTIVE: To
      investigate the immunomodulatory effect of hypertonic saline on polymorphonuclear
      cells by evaluating the changes in TLR-4 receptors and proinflammatory cytokines.
      METHODS: Polymorphonuclear cells were isolated from whole blood using
      Polymorphprep (Axis-Shield, Oslo, Norway). The isolated polymorphonuclear cells
      were plated at a density of 1 * 10(6) cells/mL in 6-well flat-bottomed culture
      plates and were stimulated with 1 MUg/mL lipopolysaccharide or N-formyl-methionyl
      leucyl-phenylalanine. The stimulated polymorphonuclear cells were cultured in
      hypertonic saline at 10, 20, or 40 mmol/L above isotonicity. After that, the
      changes in TLR-4 and cytokines were measured by quantitative real-time polymerase
      chain reaction and flow cytometry. RESULTS: The level of TLR-4 mRNA expression
      decreased after stimulation with N-formyl-methionyl-leucyl-phenylalanine, but
      hypertonic saline did not affect the TLR-4 mRNA expression. TLR-4 mRNA expression
      was clearly induced upon stimulation with lipopolysaccharide, and the addition of
      hypertonic saline restored TLR-4 mRNA expression in polymorphonuclear cells. The
      interleukin-1beta mRNA expression was decreased in the hypertonic environment. On
      the other hand, the tumor necrosis factor-alpha value was not influenced by the
      addition of hypertonic saline. CONCLUSIONS: Hypertonic saline has an
      immunomodulatory effect on polymorphonuclear cells through the TLR-4 pathway, and
      the interleukin-1beta-associated pathway is influenced more by hypertonic saline
      than is the tumor necrosis factor-alpha-associated pathway.

PMID- 25067988
TI  - Sequence-based detection of mutations in cadherin 1 to determine the prevalence
      of germline mutations in patients with invasive lobular carcinoma of the breast.
AB  - BACKGROUND: Loss of cadherin 1 (CDH1) expression, which is normally involved in
      cell adhesion and maintenance of tissue architecture, is a hallmark of invasive
      lobular carcinoma (ILCA). Because hereditary cancers may require different risk
      reduction, counseling and treatment options than sporadic cancer, it is critical
      to determine the prevalence of germline CDH1 mutations in patients with ILCA.
      METHODS: All patients with ILCA (n = 100) previously enrolled in the Clinical
      Breast Care Project were identified. Genomic DNA was isolated from peripheral
      blood samples and DNA variants were detected for each exon of CDH1 using high
      resolution melting technology followed by direct sequencing. RESULTS: Within the
      100 samples screened, four nonsynonymous variants were detected: A592T in one
      Hispanic patient, A617T in two patients, both African American, P825L in a
      Causasian patient whose grandmother had stomach cancer, and G879S in a Caucasian
      patient. Further evaluation of A617T in an additional 165 African American
      patients found that 11 patients, none with ILCA, carried this variant including
      one patient who was homozygous for the variant. CONCLUSIONS: CDH1 mutations are
      infrequent in patients with ILCA, and the variants that were detected have been
      classified as non-pathogenic. These data suggest that ILCA does not have a
      significant hereditary component and do not support CDH1 gene mutation testing in
      patients with ILCA.

PMID- 25067989
TI  - Conducting Simulation Studies in the R Programming Environment.
AB  - Simulation studies allow researchers to answer specific questions about data
      analysis, statistical power, and best-practices for obtaining accurate results in
      empirical research. Despite the benefits that simulation research can provide,
      many researchers are unfamiliar with available tools for conducting their own
      simulation studies. The use of simulation studies need not be restricted to
      researchers with advanced skills in statistics and computer programming, and such
      methods can be implemented by researchers with a variety of abilities and
      interests. The present paper provides an introduction to methods used for running
      simulation studies using the R statistical programming environment and is written
      for individuals with minimal experience running simulation studies or using R.
      The paper describes the rationale and benefits of using simulations and
      introduces R functions relevant for many simulation studies. Three examples
      illustrate different applications for simulation studies, including (a) the use
      of simulations to answer a novel question about statistical analysis, (b) the use
      of simulations to estimate statistical power, and (c) the use of simulations to
      obtain confidence intervals of parameter estimates through bootstrapping. Results
      and fully annotated syntax from these examples are provided.

PMID- 25067990
TI  - The Influence of Trauma History and Relationship Power on Latinas' Sexual Risk
      for HIV/STIs.
AB  - A community sample of Latinas completed surveys that included measures of sexual
      abuse and intimate partner violence history, relationship power, negotiating
      power regarding condom use, perceived HIV/STI risk of sexual partner, and sexual
      behavior. Over half of the women reported a history of intimate partner violence
      in the past year and/or sexual abuse in their lifetime. Intimate partner violence
      was correlated with lower overall sexual relationship power scores, while sexual
      abuse was correlated with lower condom use negotiating power. More extensive
      intimate partner violence had the strongest association with higher HIV/STI risk,
      controlling for relationship status, sexual abuse, and relationship power.

PMID- 25067991
TI  - Plasmon Mapping in Au@Ag Nanocube Assemblies.
AB  - Surface plasmon modes in metallic nanostructures largely determine their
      optoelectronic properties. Such plasmon modes can be manipulated by changing the
      morphology of the nanoparticles or by bringing plasmonic nanoparticle building
      blocks close to each other within organized assemblies. We report the EELS
      mapping of such plasmon modes in pure Ag nanocubes, Au@Ag core-shell nanocubes,
      and arrays of Au@Ag nanocubes. We show that these arrays enable the creation of
      interesting plasmonic structures starting from elementary building blocks.
      Special attention will be dedicated to the plasmon modes in a triangular array
      formed by three nanocubes. Because of hybridization, a combination of such
      nanotriangles is shown to provide an antenna effect, resulting in strong
      electrical field enhancement at the narrow gap between the nanotriangles.

PMID- 25067992
TI  - Analysis of the Retromer complex-WASH complex interaction illuminates new avenues
      to explore in Parkinson disease.
AB  - The retromer complex mediates endosomal protein sorting by concentrating membrane
      proteins (cargo) into nascent tubules formed through the action of sorting nexin
      (SNX) proteins. The WASH complex is recruited to endosomes by binding to the
      VPS35 subunit of retromer and facilitates cargo protein sorting by promoting
      formation of endosomally-localized F-actin. The VPS35 protein is mutated in
      Parkinson disease (PD) and a recent report has revealed that the PD-causing
      mutation impairs the association of retromer with the WASH complex leading to
      perturbed endosomal protein sorting. Another important player in endosomal
      protein sorting is the DNAJC13/RME-8 protein, which associates with SNX1 and has
      also recently been linked to PD. An additional recent report has now shown that
      RME-8 also interacts with the WASH complex thus establishing retromer and WASH
      complex-mediated endosomal protein sorting as a key pathway linked to the
      pathology of PD and providing new avenues to explore in the search for insights
      into the disease mechanism. 

PMID- 25067993
TI  - FLOW-BASED NETWORK MEASURES OF BRAIN CONNECTIVITY IN ALZHEIMER'S DISEASE.
AB  - We present a new flow-based method for modeling brain structural connectivity.
      The method uses a modified maximum-flow algorithm that is robust to noise in the
      diffusion data and guided by biologically viable pathways and structure of the
      brain. A flow network is first created using a lattice graph by connecting all
      lattice points (voxel centers) to all their neighbors by edges. Edge weights are
      based on the orientation distribution function (ODF) value in the direction of
      the edge. The maximum-flow is computed based on this flow graph using the flow or
      the capacity between each region of interest (ROI) pair by following the
      connected tractography fibers projected onto the flow graph edges. Network
      measures such as global efficiency, transitivity, path length, mean degree,
      density, modularity, small world, and assortativity are computed from the flow
      connectivity matrix. We applied our method to diffusion-weighted images (DWIs)
      from 110 subjects (28 normal elderly, 56 with early and 11 with late mild
      cognitive impairment, and 15 with AD) and segmented co-registered anatomical MRIs
      into cortical regions. Experimental results showed better performance compared to
      the standard fiber-counting methods when distinguishing Alzheimer's disease from
      normal aging.

PMID- 25067994
TI  - Statistical Methods for Selecting Maximum Effective Dose and Evaluating Treatment
      Effect When Dose - Response is Monotonic.
AB  - The maximum effective dose (MaxED) is an important quantity for therapeutic
      drugs. The MaxED for therapeutic drugs is defined as the dose above which no
      improvement in efficacy is obtained. In this article, we propose two experimental
      designs and analytic methods (one single-stage design and one two-stage design)
      to select the MaxED among several fixed doses and to compare the therapeutic
      effect of the selected MaxED with a control. The selection of MaxED is based on
      the isotonic regression under the restriction of monotonicity. In the single
      stage design, both the selection of the MaxED and assessing its efficacy are
      carried out at the end of experiment. In the two-stage design, the selection of
      the MaxED and assessment of its efficacy are carried out at the interim analysis
      (first stage), the experiment in the second stage is carried out only at the
      selected MaxED and control if the first-stage test is not significant. Thus, the
      two-stage design enables selection of the MaxED at an earlier stage and stopping
      the trial earlier if the treatment effect at MaxED is extreme. Williams' test
      (1972) is applied to test whether the selected MaxED is significantly different
      from control for the single-stage design and the first-stage test of the two
      stage design. The sample size calculation for each design is provided. Extensive
      simulations are carried out to illustrate the performances of the proposed
      methods.

PMID- 25067995
TI  - The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis:
      Implications for Treatment of Joint Injuries.
AB  - Excessive joint surface loadings, either single (acute impact event) or
      repetitive (cumulative contact stress), can cause the clinical syndrome of
      osteoarthritis (OA). Despite advances in treatment of injured joints, the risk of
      OA following joint injuries has not decreased in the last 50 years. Cumulative
      excessive articular surface contact stress that leads to OA results from post
      traumatic joint incongruity and instability, and joint dysplasia, but also may
      cause OA in patients without known joint abnormalities. In vitro investigations
      show that excessive articular cartilage loading triggers release of reactive
      oxygen species (ROS) from mitochondria, and that these ROS cause chondrocyte
      death and matrix degradation. Preventing release of ROS or inhibiting their
      effects preserves chondrocytes and their matrix. Fibronectin fragments released
      from articular cartilage subjected to excessive loads also stimulate matrix
      degradation; inhibition of molecular pathways initiated by these fragments
      prevents this effect. Additionally, injured chondrocytes release alarmins that
      activate chondroprogentior cells in vitro that propogate and migrate to regions
      of damaged cartilage. These cells also release chemokines and cytokines that may
      contribute to inflammation that causes progressive cartilage loss. Distraction
      and motion of osteoarthritic human ankles can promote joint remodeling, decrease
      pain and improve joint function in patients with end-stage post-traumatic OA.
      These advances in understanding of how altering mechanical stresses can lead to
      remodeling of osteoarthritic joints and how excessive stress causes loss of
      articular cartilage, including identification of mechanically induced mediators
      of cartilage loss, provide the basis for new biologic and mechanical approaches
      to the prevention and treatment of OA.

PMID- 25067996
TI  - Mesenchymal stem cells for treatment of aortic aneurysms.
AB  - An aortic aneurysm (AA) is a silent but life-threatening disease that involves
      rupture. It occurs mainly in aging and severe atherosclerotic damage of the
      aortic wall. Even though surgical intervention is effective to prevent rupture,
      surgery for the thoracic and thoraco-abdominal aorta is an invasive procedure
      with high mortality and morbidity. Therefore, an alternative strategy for
      treatment of AA is required. Recently, the molecular pathology of AA has been
      clarified. AA is caused by an imbalance between the synthesis and degradation of
      extracellular matrices in the aortic wall. Chronic inflammation enhances the
      degradation of matrices directly and indirectly, making control of the chronic
      inflammation crucial for aneurysmal development. Meanwhile, mesenchymal stem
      cells (MSCs) are known to be obtained from an adult population and to
      differentiate into various types of cells. In addition, MSCs have not only the
      potential anti-inflammatory and immunosuppressive properties but also can be
      recruited into damaged tissue. MSCs have been widely used as a source for cell
      therapy to treat various diseases involving graft-versus-host disease, stroke,
      myocardial infarction, and chronic inflammatory disease such as Crohn's disease
      clinically. Therefore, administration of MSCs might be available to treat AA
      using anti-inflammatory and immnosuppressive properties. This review provides a
      summary of several studies on "Cell Therapy for Aortic Aneurysm" including our
      recent data, and we also discuss the possibility of this kind of treatment. 

PMID- 25067997
TI  - Colorectal hepatic metastasis: Evolving therapies.
AB  - The approach for colorectal hepatic metastasis has advanced tremendously over the
      past decade. Multidrug chemotherapy regimens have been successfully introduced
      with improved outcomes. Concurrently, adjunct multimodal therapies have improved
      survival rates, and increased the number of patients eligible for curative liver
      resection. Herein, we described major advancements of surgical and oncologic
      management of such lesions, thereby discussing modern chemotherapeutic regimens,
      adjunct therapies and surgical aspects of liver resection. 

PMID- 25067999
TI  - Focal liver lesions detection and characterization: The advantages of gadoxetic
      acid-enhanced liver MRI.
AB  - Since its clinical introduction, several studies in literature have investigated
      gadolinium ethoxybenzhyl diethylenetriaminepentaacetic acid or gadoxetic acid (Gd
      EOB-DTPA) properties. Following contrast injection, it provides dynamic vascular
      phases (arterial, portal and equilibrium phases) and hepatobiliary phase, the
      latter due to its uptake by functional hepatocytes. The main advantages of Gd-EOB
      DTPA of focal liver lesion detection and characterization are discussed in this
      paper. Namely, we focus on the possibility of distinguishing focal nodular
      hyperplasia (FNH) from hepatic adenoma (HA), the identification of early
      hepatocellular carcinoma (HCC) and the pre-operative assessment of metastasis in
      liver parenchyma. Regarding the differentiation between FNH and HA, adenoma
      typically appears hypointense in hepatobiliary phase, whereas FNH is isointense
      or hyperintense to the surrounding hepatic parenchyma. As for the identification
      of early HCCs, many papers recently published in literature have emphasized the
      contribution of hepatobiliary phase in the characterization of nodules without a
      typical hallmark of HCC. Atypical nodules (no hypervascularizaton observed on
      arterial phase and/or no hypovascular appearance on portal phase) with low signal
      intensity in the hepatobiliary phase, have a high probability of malignancy.
      Finally, regarding the evaluation of focal hepatic metastases, magnetic resonance
      pre-operative assessment using gadoxetic acid allows for more accurate diagnosis.

PMID- 25067998
TI  - Juvenile autoimmune hepatitis: Spectrum of the disease.
AB  - Juvenile autoimmune hepatitis (JAIH) is a progressive inflammatory liver disease,
      affecting mainly young girls, from infancy to late adolescence, characterized by
      active liver damage, as shown by high serum activity of aminotransferases, by
      elevated immunoglobulin G levels, high titers of serum non organ-specific and
      organ-specific autoantibodies, and by interface hepatitis on liver biopsy. It is
      a multifactorial disease of unknown etiology in which environmental factors act
      as a trigger in genetically predisposed individuals. Two types of JAIH are
      identified according to the autoantibody panel detected at diagnosis: AIH-1,
      characterized by the presence of anti-smooth muscle antibody and/or antinuclear
      antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the
      presence of anti-liver cytosol type 1 antibody. Epidemiological distribution,
      genetic markers, clinical presentation and pattern of serum cytokines
      differentiate the two types of AIH suggesting possible pathogenetic mechanisms.
      The most effective therapy for AIH is pharmacological suppression of the immune
      response. Treatment should be started as soon as the diagnosis is made to avoid
      severe liver damage and progression of fibrosis. The aim of this review is to
      outline the most significant and peculiar features of JAIH, based largely on our
      own personal database and on a review of current literature. 

PMID- 25068000
TI  - Differential diagnosis and management of liver tumors in infants.
AB  - During the first year of life, most of the liver neoplasms are benign in origin,
      but some of these histologically benign lesions may be challenging in their
      management. Although most hepatic hemangiomas can be safely observed until
      involution is documented, some patients will need treatment due to progressive
      hepatomegaly, hypothyroidism and/or cardiac failure. Large mesenchymal hamartomas
      may require extensive hepatic resection and an appropriate surgical plan is
      critical to obtain good results. For malignant neoplasms such as hepatoblastoma,
      complete surgical resection is the mainstay of curative therapy. The decision
      about whether to perform an upfront or delayed resection of a primary liver
      malignant tumor is based on many considerations, including the ease of resection,
      surgical expertise, tumor histology and stage, and the likely chemosensitivity of
      the tumor. This article reviews the initial management of the more common hepatic
      tumors of infancy, focusing on the differential diagnosis and treatment options. 

PMID- 25068001
TI  - CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic
      steatohepatitis.
AB  - AIM: To determine intra-hepatic blood flow and liver stiffness in patients with
      non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis
      (NASH) using contrast-enhanced ultrasound and fibroscan. METHODS: This
      prospective study included 15 patients with NAFLD, 17 patients with NASH and 16
      healthy controls. In each patient, real-time ultrasound was used to locate the
      portal vein (PV) and the right liver lobe, and 5 mL of SonoVue((r)) was then
      injected intravenous in a peripheral vein of the left arm over a 4-s span.
      Digital recording was performed for 3 min thereafter. The recording was
      subsequently retrieved to identify an area of interest in the PV area and in the
      right liver parenchyma (LP) to assess the blood flow by processing the data using
      dedicated software (Qontrast((r)), Bracco, Italy). The following parameters were
      evaluated: percentage of maximal contrast activity (Peak%), time to peak (TTP,
      s), regional blood volume (RBV, cm(3)), regional blood flow (RBF, cm(3)/s) and
      mean transit time (MTT, s). At 24-48 h post-injection, liver stiffness was
      evaluated using Fibroscan and measured in kPa. The statistical evaluation was
      performed using Student's t test. RESULTS: In the PV, the Peak%, RBV and RBF were
      significantly reduced in the NAFLD and NASH patients compared with the controls
      (Peak%: NAFLD 26.3 +/- 6.6, NASH 28.1 +/- 7.3 vs controls 55.8 +/- 9.9, P <
      0.001; RBV: NAFLD 4202.3 +/- 3519.7, NASH 3929.8 +/- 1941.3 vs controls 7473 +/-
      3281, P < 0.01; RBF: NAFLD 32.5 +/- 10.8, NASH 32.7 +/- 12.1 vs controls 73.1 +/-
      13.9, P < 0.001). The TTP in the PV was longer in both patient groups but reached
      statistical significance only in the NASH patients compared with the controls
      (NASH 79.5 +/- 37.8 vs controls 43.2 +/- 30, P < 0.01). In the LP, the Peak%, RBV
      and RBF were significantly reduced in the NAFLD and NASH patients compared with
      the controls (Peak%: NAFLD 43.2 +/- 7.3, NASH 41.7 +/- 7.7 vs controls 56.6 +/-
      6.3, P < 0.001; RBV: NAFLD 4851.5 +/- 2009, NASH 5069.4 +/- 2292.5 vs controls
      6922.9 +/- 2461.5, P < 0.05; RBF: NAFLD 55.7 +/- 10.1, NASH 54.5 +/- 12.1 vs
      controls 75.9 +/- 10.5, P < 0.001). The TTP was longer in both patient groups but
      did not reach statistical significance. The MTT in both the PV and LP in the
      NAFLD and NASH patients was not different from that in the controls. Liver
      stiffness was significantly increased relative to the controls only in the NASH
      patients (NASH: 6.4 +/- 2.2 vs controls 4.6 +/- 1.5, P < 0.05). CONCLUSION: Blood
      flow derangement within the liver present not only in NASH but also in NAFLD
      suggests that a vascular flow alteration precedes liver fibrosis development.

PMID- 25068002
TI  - Clinical outcomes of compensated and decompensated cirrhosis: A long term study.
AB  - AIM: To study these characteristics and prognostic patterns in a Greek patient
      population. METHODS: We analyzed a large cohort of cirrhotic patients referred to
      the department of Gastroenterology and Hepatology and the outpatient clinics of
      this tertiary hospital, between 1991 and 2008. We included patients with
      established cirrhosis, either compensated or decompensated, and further
      decompensation episodes were registered. A data base was maintained and updated
      prospectively throughout the study period. We analyzed differences in cirrhosis
      aetiology, time to and mode of decompensation, hepatocellular carcinoma (HCC)
      occurrence and ultimately patient survival. RESULTS: Five hundreds and twenty-two
      patients with median age 67 (range, 29-91) years and average follow up 9 years-10
      mo (range, 1-206 mo) were studied. Commonest aetiology was hepatitis C virus
      (HCV, 41%) followed by alcohol (31%). The median survival time in compensated
      cirrhotics was 115 mo (95%CI: 95-133), whereas in decompensated patients was 55
      mo (95%CI: 36-75). HCV patients survived longer while HBV patients had over twice
      the risk of death of HCV patients. The median time to decompensation was 65 mo
      (95%CI: 51-79), with alcoholics having the highest risk (RR = 2.1 vs HCV
      patients). Hepatitis B virus (HBV) patients had the highest risk of HCC,
      alcoholics the lowest. Leading causes of death: liver failure, hepatorenal
      syndrome, sepsis and HCC progression. CONCLUSION: Cirrhosis aetiology and
      decompensation at presentation were predictors of survival. Alcoholics had the
      highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV
      cirrhotics the highest decompensation-free time.

PMID- 25068003
TI  - Patients with multiple synchronous colonic cancer hepatic metastases benefit from
      enrolment in a "liver first" approach protocol.
AB  - AIM: To assess a protocol for treating patients with multiple synchronous colonic
      cancer liver metastases, which are unresectable in one stage. METHODS: Patients
      enrolled in the "liver first" protocol presented with colon-only (not rectal)
      cancer and multiple synchronous hepatic metastases (type II or III). All patients
      showed good performance status (ECOG PS 0-1) and were treated with curative
      intent. Complete oncologic staging including positron emission tomography
      computed tomography was performed in order to rule out extrahepatic disease. If
      bowel obstruction was imminent, an intraluminal colonic stent was placed
      endoscopically. Subsequently, all patients received standardised neo-adjuvant
      chemotherapy, that is, FOLFOX or XELOX regimens combined with an antiangiogenic
      agent (bevacizumab or cetuximab). Provided that a response to chemotherapy was
      observed, patients underwent either one or two hepatectomies with or without
      portal vein embolization followed by the indicated colectomy. Further
      chemotherapy was administered after each procedure. Re-staging was performed
      after each chemotherapeutic treatment. Disease progression at any stage resulted
      in discontinuation of the protocol and conversion to palliative disease
      management. RESULTS: Prospectively recorded data from 11 consecutive patients (8
      men) were analysed for this study. Their mean age at the time of their first
      assessment was 65.7 (SD +/- 15.3) years. Six (54.6%) patients presented with type
      III metastatic disease. The minimum and maximum follow-up periods were 7.3 and
      39.6 mo, respectively. The mean overall survival of all patients was 16.5 (95%CI:
      10.0-23.2) mo. A colonic stent had to be placed in 5 (45.5%) patients due to the
      onset of an intraluminal obstruction. Four (36.4%) patients succeeded in
      completing all planned surgical operations. Their mean overall survival was 27.2
      (95%CI: 15.1-39.3) mo and the mean disease-free survival was 7.7 (95%CI: 3.0
      12.5) mo. Patients, who were obliged to shift to palliative treatment due to
      disease progression, had a mean overall survival of 10.5 (95%CI: 8.6-12.4) mo.
      None of these patients underwent palliative colectomy. No postoperative mortality
      was recorded. CONCLUSION: The implementation of a structured "liver first"
      approach protocol for the treatment of patients with extensive, liver-limited
      colon cancer metastatic disease may be beneficial.

PMID- 25068004
TI  - Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C.
AB  - AIM: To study the safety and efficacy of pegylated interferon alfa-2b,
      indigenously developed in India, plus ribavirin in treatment of hepatitis C virus
      (HCV). METHODS: One-hundred HCV patients were enrolled in an open-label,
      multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5
      MUg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with
      genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based
      ribavirin (800 mg/d for <= 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85
      105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for
      patients with genotypes 1 and 4. Serological and biochemical responses of
      patients were assessed. RESULTS: Eighty-two patients (35 in genotypes 1 and 4 and
      47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved
      rapid virologic response (RVR): while the figures were 74.1% for early virologic
      response (EVR) and 44.4% for sustained virologic response (SVR). For genotypes 2
      and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%,
      and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%,
      and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of
      patients attained normal levels of alanine aminotransferase by 4-12 wk of
      therapy. Most patients showed a good tolerance for the treatment, although mild
      to-moderate adverse events were exhibited; only two patients discontinued the
      study medication due to serious adverse events (SAEs). Eleven SAEs were observed
      in nine patients; however, only four SAEs were related to study medication.
      CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination
      with ribavirin, is a safe and effective drug in the treatment of HCV.

PMID- 25068005
TI  - Acute fatty liver of pregnancy associated with severe acute pancreatitis: A case
      report.
AB  - Acute fatty liver of pregnancy is a rare disease that affects women in the third
      trimester of pregnancy. Although infrequent, the disease can cause maternal
      mortality. The diagnosis is not always clear until the pregnancy is terminated,
      and significant complications, such as acute pancreatitis, can occur. Pancreatic
      involvement typically only occurs in severe cases after the development of
      hepatic and renal impairment. To date, little knowledge is available regarding
      how the disease causes pancreatitis. Treatment involves supportive measures and
      pregnancy interruption. In this report, we describe a case of a previously
      healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted
      with severe abdominal pain and vomiting. This case illustrates the clinical and
      laboratory overlap between acute fatty liver of pregnancy and pancreatitis,
      highlighting the difficulties in differentiating each disease. Furthermore, the
      hypothesis for this overlapping is presented, and the therapeutic options are
      discussed. 

PMID- 25068006
TI  - Portal vein thrombosis with protein C-S deficiency in a non-cirrhotic patient.
AB  - There are several conditions that can lead to portal vein thrombosis (PVT),
      including including infection, malignancies, and coagulation disorders. Anew
      condition of interest is protein C and S deficiencies, associated with
      hypercoagulation and recurrent venous thromboembolism. We report the case of a
      non-cirrhotic 63-year-old male diagnosed with acute superior mesenteric vein
      thrombosis and PVT and combined deficiencies in proteins C and S, recanalized by
      short-term low molecular heparin plus oral warfarin therapy. 

PMID- 25068007
TI  - From Fantasy to Action: Mental Contrasting with Implementation Intentions (MCII)
      Improves Academic Performance in Children.
AB  - The current intervention tested whether a metacognitive self-regulatory strategy
      of goal pursuit can help economically disadvantaged children convert positive
      thoughts and images about their future into effective action. Mental contrasting
      with implementation intentions (MCII) entails mental contrasting a desired future
      with relevant obstacles of reality and forming implementation intentions (if-then
      plans) specifying when and where to overcome those obstacles. Seventy-seven fifth
      graders from an urban middle school were randomly assigned to learn either MCII
      or a Positive Thinking control strategy. Compared to children in the control
      condition, children taught how to apply MCII to their academic wishes and
      concerns significantly improved their report card grades (eta2 = .07), attendance
      (eta2 = .05), and conduct (eta2 = .07). These findings suggest that MCII holds
      considerable promise for helping disadvantaged middle school children improve
      their academic performance.

PMID- 25068008
TI  - Detection of Negative Charge Carriers in Superfluid Helium Droplets: The
      Metastable Anions He*- and He2*-
AB  - Helium droplets provide the possibility to study phenomena at the very low
      temperatures at which quantum mechanical effects are more pronounced and fewer
      quantum states have significant occupation probabilities. Understanding the
      migration of either positive or negative charges in liquid helium is essential to
      comprehend charge-induced processes in molecular systems embedded in helium
      droplets. Here, we report the resonant formation of excited metastable atomic and
      molecular helium anions in superfluid helium droplets upon electron impact.
      Although the molecular anion is heliophobic and migrates toward the surface of
      the helium droplet, the excited metastable atomic helium anion is bound within
      the helium droplet and exhibits high mobility. The atomic anion is shown to be
      responsible for the formation of molecular dopant anions upon charge transfer and
      thus, we clarify the nature of the previously unidentified fast exotic negative
      charge carrier found in bulk liquid helium.

PMID- 25068009
TI  - Mechanisms of hepatic ischemia-reperfusion injury and protective effects of
      nitric oxide.
AB  - Hepatic ischemia-reperfusion injury (IRI) is a pathophysiological event post
      liver surgery or transplantation and significantly influences the prognosis of
      liver function. The mechanisms of IRI remain unclear, and effective methods are
      lacking for the prevention and therapy of IRI. Several factors/pathways have been
      implicated in the hepatic IRI process, including anaerobic metabolism,
      mitochondria, oxidative stress, intracellular calcium overload, liver Kupffer
      cells and neutrophils, and cytokines and chemokines. The role of nitric oxide
      (NO) in protecting against liver IRI has recently been reported. NO has been
      found to attenuate liver IRI through various mechanisms including reducing
      hepatocellular apoptosis, decreasing oxidative stress and leukocyte adhesion,
      increasing microcirculatory flow, and enhancing mitochondrial function. The
      purpose of this review is to provide insights into the mechanisms of liver IRI,
      indicating the potential protective factors/pathways that may help to improve
      therapeutic regimens for controlling hepatic IRI during liver surgery, and the
      potential therapeutic role of NO in liver IRI. 

PMID- 25068010
TI  - Chronic pancreatitis: A surgical disease? Role of the Frey procedure.
AB  - Although medical treatment and endoscopic interventions are primarily offered to
      patients with chronic pancreatitis, approximately 40% to 75% will ultimately
      require surgery during the course of their disease. Although
      pancreaticoduodenectomy has been considered the standard surgical procedure
      because of its favorable results on pain control, its high postoperative
      complication and pancreatic exocrine or/and endocrine dysfunction rates have led
      to a growing enthusiasm for duodenal preserving pancreatic head resection. The
      aim of this review is to better understand the rationale underlying of the Frey
      procedure in chronic pancreatitis and to analyze its outcome. Because of its
      hybrid nature, combining both resection and drainage, the Frey procedure has been
      conceptualized based on the pathophysiology of chronic pancreatitis. The short
      and long-term outcome, especially pain relief and quality of life, are better
      after the Frey procedure than after any other surgical procedure performed for
      chronic pancreatitis. 

PMID- 25068011
TI  - Lymphoepithelial cysts and cystic lymphangiomas: Under-recognized benign cystic
      lesions of the pancreas.
AB  - AIM: To identify their diagnostic and prognostic clinical characteristics in a
      large series. METHODS: Retrospective review of clinicopathologic and imaging
      characteristics of patients diagnosed with lymphoepithelial cysts and cystic
      lymphangiomas of the pancreas at Massachusetts General Hospital. RESULTS: Twelve
      patients were identified between 1/1/1997 and 8/1/2007. Their median age was 55.5
      years (range 19-78 years), and 6 were females. The lesion was incidentally
      discovered in half of the patients. Contrast enhanced computed tomography
      demonstrated that the cysts had thin walls, without calcifications, pancreatic
      duct dilation or pancreatic parenchyma invasion. Endoscopic ultrasound with fine
      needle aspiration (EUS/FNA) confirmed the diagnosis of a lymphoepithelial cyst in
      3 patients, one of whom was spared an operation and continues to do well after 6
      years. Eleven patients had a resection: 3 pancreaticoduodenectomies, 7 distal
      pancreatectomies, and 1 enucleation. The median size of the cysts was 3 cm (range
      2-20 cm). At a median follow-up of 57 mo no recurrences or other pancreas-related
      conditions occurred. CONCLUSION: Lymphoepithelial cysts and cystic lymphangiomas
      of the pancreas can be diagnosed with a combination of contrast-enhanced computed
      tomography scans and EUS/FNA. If the lesion is asymptomatic, an operation might
      be avoided.

PMID- 25068012
TI  - Isotretinoin and ulcerative colitis: A case report and review of the literature.
AB  - This case report describes a case of ulcerative colitis the onset of which
      occurred after the use of isotretinoin for acne treatment. Our patient, a healthy
      male young adult, after several months of isotretinoin use, developed
      gastrointestinal disorders and after thorough medical workup was diagnosed with
      ulcerative colitis. The literature regarding a possible correlation between
      isotretinoin use and ulcerative colitis is scarce. Nevertheless, recent
      epidemiological studies have shed more light on this possible association. 

PMID- 25068014
TI  - Hypertension and medical expenditure in the Japanese population: Review of
      prospective studies.
AB  - Hypertension is a major determinant of health and is likely to have an effect on
      medical economics. The economic burden due to hypertension may be attributable
      not only to antihypertensive medication but also to the very expensive procedures
      required for cases of cardiovascular disease that occur more frequently in
      hypertensive compared with normotensive individuals. The objective of this
      article was to review articles published on prospective cohort studies that
      measured medical expenditure attributable to hypertension in community-dwelling
      populations in Japan. Many medical services in these populations are provided
      under the medical insurance system that requires the enrolment of all Japanese
      residents. Personal medical expenditure attributable to hypertension increases
      with worsening severity of the condition. Medical expenditure was increased
      further in cases of hypertensive patients who have another concomitant
      cardiovascular risk factor. In particular, hypertension, especially moderate-to
      severe untreated hypertension, increases the risk of long-term hospitalization
      resulting in considerably higher medical expenditure, compared with non
      hospitalized cases. Therefore, assuming that the use of antihypertensive
      medication is essential for hypertensive patients to prevent serious vascular
      diseases, a cost-effective high-risk strategy needs to be considered to reduce
      both ill-health and the economic burden due to hypertension. However, from a
      population perspective, medical expenditure attributable to hypertension comes
      mainly from pre-to-mild hypertension. Therefore, there is also a need to consider
      a population strategy that aims to shift the entire population to lower levels of
      blood pressure. 

PMID- 25068013
TI  - Antihypertensive drugs and glucose metabolism.
AB  - Hypertension plays a major role in the development and progression of micro- and
      macrovascular disease. Moreover, increased blood pressure often coexists with
      additional cardiovascular risk factors such as insulin resistance. As a result
      the need for a comprehensive management of hypertensive patients is critical.
      However, the various antihypertensive drug categories have different effects on
      glucose metabolism. Indeed, angiotensin receptor blockers as well as angiotensin
      converting enzyme inhibitors have been associated with beneficial effects on
      glucose homeostasis. Calcium channel blockers (CCBs) have an overall neutral
      effect on glucose metabolism. However, some members of the CCBs class such as
      azelnidipine and manidipine have been shown to have advantageous effects on
      glucose homeostasis. On the other hand, diuretics and beta-blockers have an
      overall disadvantageous effect on glucose metabolism. Of note, carvedilol as well
      as nebivolol seem to differentiate themselves from the rest of the beta-blockers
      class, being more attractive options regarding their effect on glucose
      homeostasis. The adverse effects of some blood pressure lowering drugs on glucose
      metabolism may, to an extent, compromise their cardiovascular protective role. As
      a result the effects on glucose homeostasis of the various blood pressure
      lowering drugs should be taken into account when selecting an antihypertensive
      treatment, especially in patients which are at high risk for developing diabetes.

PMID- 25068016
TI  - Risks and diagnosis of coronary artery disease in Hodgkin lymphoma survivors.
AB  - Higher mortality rates are reported because of cardiovascular diseases in
      individuals living in industrialized areas of the World. In cancer patients,
      cardiotoxic chemotherapeutic agents and/or mediastinal radiotherapy are
      additional risk factors for the development of coronary artery disease. An
      improved survival rate for patients with Hodgkin lymphoma was reported in recent
      decades. Determining and handling the long-term effects of cancer treatment have
      become more important nowadays, parallel to the good results reached in survival
      rates. Mediastinal radiotherapy and cardiotoxic chemotherapeutic agents are
      routinely used to treat Hodgkin lymphoma but are commonly associated with a
      variety of cardiovascular complications. Drugs used in cancer treatment and
      radiotherapy may cause deleterious effects on contractile capacity and conduction
      system of the heart. Approximately ten years after the completion of all
      therapies, the cardiovascular disease risk peaks in patients who survived from
      Hodgkin lymphoma. The value of coronary computed tomography angiography as a
      diagnostic tool in determining coronary artery disease as early as possible is
      underlined in this review, in patients who are in remission and carry the risk of
      coronary artery disease probably because of chemo/radiotherapy used in their
      treatment. Survivors of Hodgkin lymphoma especially treated with combined
      chemoradiotherapy at younger ages are candidates for coronary computed tomography
      angiography. 

PMID- 25068015
TI  - Adipose tissue and vascular inflammation in coronary artery disease.
AB  - Obesity has become an important public health issue in Western and developing
      countries, with well known metabolic and cardiovascular complications. In the
      last decades, evidence have been growing about the active role of adipose tissue
      as an endocrine organ in determining these pathological consequences. As a
      consequence of the expansion of fat depots, in obese subjects, adipose tissue
      cells develope a phenotypic modification, which turns into a change of the
      secretory output. Adipocytokines produced by both adipocytes and adipose stromal
      cells are involved in the modulation of glucose and lipid handling, vascular
      biology and, moreover, participate to the systemic inflammatory response, which
      characterizes obesity and metabolic syndrome. This might represent an important
      pathophysiological link with atherosclerotic complications and cardiovascular
      events. A great number of adipocytokines have been described recently, linking
      inflammatory mileu and vascular pathology. The understanding of these pathways is
      crucial not only from a pathophysiological point of view, but also to a better
      cardiovascular disease risk stratification and to the identification of possible
      therapeutic targets. The aim of this paper is to review the role of
      Adipocytokines as a possible link between obesity and vascular disease. 

PMID- 25068017
TI  - Non-invasive evaluation of arrhythmic risk in dilated cardiomyopathy: From
      imaging to electrocardiographic measures.
AB  - Malignant ventricular arrhythmias are a major adverse event and worsen the
      prognosis of patients affected by ischemic and non-ischemic dilated
      cardiomyopathy. The main parameter currently used to stratify arrhythmic risk and
      guide decision making towards the implantation of a cardioverter defibrillator is
      the evaluation of the left ventricular ejection fraction. However, this strategy
      is characterized by several limitations and consequently additional parameters
      have been suggested in order to improve arrhythmic risk stratification. The aim
      of this review is to critically revise the prognostic significance of non
      invasive diagnostic tools in order to better stratify the arrhythmic risk
      prognosis of dilated cardiomyopathy patients. 

PMID- 25068018
TI  - Mechanisms underlying the impaired contractility of diabetic cardiomyopathy.
AB  - Cardiac dysfunction is a well-known consequence of diabetes, with sustained
      hyperglycaemia leading to the development of a cardiomyopathy that is independent
      of cardiovascular disease or hypertension. Animal models of diabetes are commonly
      used to study the pathophysiology of diabetic cardiomyopathy, with the hope that
      increased knowledge will lead ultimately to better therapeutic strategies being
      developed. At physiological temperature, left ventricular trabeculae isolated
      from the streptozotocin rat model of type 1 diabetes showed decreased stress and
      prolonged relaxation, but with no evidence that decreased contractility was a
      result of altered myocardial Ca(2+) handling. Although sarcoplasmic reticulum
      (SR) Ca(2+) reuptake appeared slower in diabetic trabeculae, it was offset by an
      increase in action-potential duration, thereby maintaining SR Ca(2+) content and
      favouring increased contraction force. Frequency analysis of t-tubule
      distribution by confocal imaging of ventricular tissue labeled with wheat germ
      agglutinin or ryanodine receptor antibodies showed a reduced T-power for diabetic
      tissue, but the differences were minor in comparison to other models of heart
      failure. The contractile dysfunction appeared to be the result of disrupted F
      actin in conjunction with the increased type I collagen, with decreased
      myofilament Ca(2+) sensitivity contributing to the slowed relaxation. 

PMID- 25068019
TI  - Distribution of late gadolinium enhancement in various types of cardiomyopathies:
      Significance in differential diagnosis, clinical features and prognosis.
AB  - The recent development of cardiac magnetic resonance (CMR) techniques has allowed
      detailed analyses of cardiac function and tissue characterization with high
      spatial resolution. We review characteristic CMR features in ischemic and non
      ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and
      distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental
      wall motion abnormalities or wall thinning in a particular coronary arterial
      territory, and the subendocardial or transmural LGE. LGE in NICM generally does
      not correspond to any particular coronary artery distribution and is located
      mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution
      is valuable to differentiate NICM with diffusely impaired systolic function,
      including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM),
      cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular
      (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A
      transient low signal intensity LGE in regions of severe LV dysfunction is a
      particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular
      cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with
      functional and morphological changes of RV becomes apparent. Finally, the
      analyses of LGE distribution have potentials to predict cardiac outcomes and
      response to treatments. 

PMID- 25068020
TI  - Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment.
AB  - In 1990, takotsubo cardiomyopathy (TCM) was first discovered and reported by a
      Japanese cardiovascular specialist. Since then, this heart disease has gained
      worldwide acceptance as an independent disease entity. TCM is an important entity
      that differs from acute myocardial infarction. It occurs more often in
      postmenopausal elderly women, is characterized by a transient hypokinesis of the
      left ventricular (LV) apex, and is associated with emotional or physical stress.
      Wall motion abnormality of the LV apex is generally transient and resolves within
      a few days to several weeks. Its prognosis is generally good. However, there are
      some reports of serious TCM complications, including hypotension, heart failure,
      ventricular rupture, thrombosis involving the LV apex, and torsade de pointes. It
      has been suggested that coronary spasm, coronary microvascular dysfunction,
      catecholamine toxicity and myocarditis might contribute to the pathogenesis of
      TCM. However, its pathophysiology is not clearly understood. 

PMID- 25068022
TI  - Chronic total occlusion: To treat or not to treat.
AB  - Over the last two decades, there has been increasing interest in new techniques
      for the percutaneous treatment of coronary chronic total occlusions (CTO), which
      have a success rate that is much higher than that of a few years ago. The rise in
      percutaneous treatment for these lesions is due to its ability to improve the
      symptoms and prognosis of patients in the chronic and stable phase of coronary
      disease. Current data suggest that successful percutaneous coronary intervention
      for CTO is associated with improvement in patient symptoms, quality of life, left
      ventricular function, and survival, compared with those with unsuccessful CTO
      PCI. However, all the scientific evidence supporting this treatment comes from
      observational studies, and no randomized study comparing percutaneous treatment
      with medical treatment has yet been published. A major limitation of these
      studies is their observational design, with limited information with regard to
      potential baseline differences between the successful vs unsuccessful cohorts.
      Pending randomized studies, patients should be selected very carefully,
      especially if they are asymptomatic or very few symptoms, and the benefits
      obtained in terms of complications during the procedure, the quality of life
      obtained and further ischemic events avoided should be evaluated systematically.
      In this review, we will consider the available information supporting
      percutaneous treatment for chronic occlusions, as well as the areas of
      uncertainty where more research projects are required. 

PMID- 25068023
TI  - Significance of lead aVR in acute coronary syndrome.
AB  - The 12-lead electrocardiogram (ECG) is a crucial tool in the diagnosis and risk
      stratification of acute coronary syndrome (ACS). Unlike other 11 leads, lead aVR
      has been long neglected until recent years. However, recent investigations have
      shown that an analysis of ST-segment shift in lead aVR provides useful
      information on the coronary angiographic anatomy and risk stratification in ACS.
      ST-segment elevation in lead aVR can be caused by (1) transmural ischemia in the
      basal part of the interventricular septum caused by impaired coronary blood flow
      of the first major branch originating from the left anterior descending coronary
      artery; (2) transmural ischemia in the right ventricular outflow tract caused by
      impaired coronary blood flow of the large conal branch originating from the right
      coronary artery; and (3) reciprocal changes opposite to ischemic or non-ischemic
      ST-segment depression in the lateral limb and precordial leads. On the other
      hand, ST-segment depression in lead aVR can be caused by transmural ischemia in
      the inferolateral and apical regions. It has been recently shown that an analysis
      of T wave in lead aVR also provides useful prognostic information in the general
      population and patients with prior myocardial infarction. Cardiologists should
      pay more attention to the tracing of lead aVR when interpreting the 12-lead ECG
      in clinical practice. 

PMID- 25068021
TI  - Stem cell mechanisms during left ventricular remodeling post-myocardial
      infarction: Repair and regeneration.
AB  - Post-myocardial infarction (MI), the left ventricle (LV) undergoes a series of
      events collectively referred to as remodeling. As a result, damaged myocardium is
      replaced with fibrotic tissue consequently leading to contractile dysfunction and
      ultimately heart failure. LV remodeling post-MI includes inflammatory, fibrotic,
      and neovascularization responses that involve regulated cell recruitment and
      function. Stem cells (SCs) have been transplanted post-MI for treatment of LV
      remodeling and shown to improve LV function by reduction in scar tissue formation
      in humans and animal models of MI. The promising results obtained from the
      application of SCs post-MI have sparked a massive effort to identify the optimal
      SC for regeneration of cardiomyocytes and the paradigm for clinical applications.
      Although SC transplantations are generally associated with new tissue formation,
      SCs also secrete cytokines, chemokines and growth factors that robustly regulate
      cell behavior in a paracrine fashion during the remodeling process. In this
      review, the different types of SCs used for cardiomyogenesis, markers of
      differentiation, paracrine factor secretion, and strategies for cell recruitment
      and delivery are addressed. 

PMID- 25068025
TI  - Neuregulin-1/erbB activities with focus on the susceptibility of the heart to
      anthracyclines.
AB  - Neuregulin-1 (NRG1) signaling through the tyrosine kinase receptors erbB2 and
      erbB4 is required for cardiac morphogenesis, and it plays an essential role in
      maintaining the myocardial architecture during adulthood. The tyrosine kinase
      receptor erbB2 was first linked to the amplification and overexpression of erbb2
      gene in a subtype of breast tumor cells, which is indicative of highly
      proliferative cells and likely a poor prognosis following conventional
      chemotherapy. The development of targeted therapies to block the survival of
      erbB2-positive cancer cells revealed that impaired NRG1 signaling through
      erbB2/erbB4 heterodimers combined with anthracycline chemotherapy may lead to
      dilated cardiomyopathy in a subpopulation of treated patients. The ventricular
      specific deletion of either erbb2 or erbb4 manifested dilated cardiomyopathy,
      which is aggravated by the administration of doxorubicin. Based on the
      exacerbated toxicity displayed by the combined treatment, it is expected that the
      relevant pathways would be affected in a synergistic manner. This review examines
      the NRG1 activities that were monitored in different model systems, focusing on
      the emerging pathways and molecular targets, which may aid in understanding the
      acquired dilated cardiomyopathy that occurs under the conditions of NRG1
      deficient signaling. 

PMID- 25068024
TI  - Calpain system and its involvement in myocardial ischemia and reperfusion injury.
AB  - Calpains are ubiquitous non-lysosomal Ca(2+)-dependent cysteine proteases also
      present in myocardial cytosol and mitochondria. Numerous experimental studies
      reveal an essential role of the calpain system in myocardial injury during
      ischemia, reperfusion and postischemic structural remodelling. The increasing
      Ca(2+)-content and Ca(2+)-overload in myocardial cytosol and mitochondria during
      ischemia and reperfusion causes an activation of calpains. Upon activation they
      are able to injure the contractile apparatus and impair the energy production by
      cleaving structural and functional proteins of myocytes and mitochondria. Besides
      their causal involvement in acute myocardial dysfunction they are also involved
      in structural remodelling after myocardial infarction by the generation and
      release of proapoptotic factors from mitochondria. Calpain inhibition can prevent
      or attenuate myocardial injury during ischemia, reperfusion, and in later stages
      of myocardial infarction. 

PMID- 25068026
TI  - Assessment of coronary artery disease using coronary computed tomography
      angiography and biochemical markers.
AB  - Chronic inflammatory mechanisms in the arterial wall lead to atherosclerosis, and
      include endothelial cell damage, inflammation, apoptosis, lipoprotein deposition,
      calcification and fibrosis. Cardiac computed tomography angiography (CCTA) has
      been shown to be a promising tool for non-invasive assessment of theses specific
      compositional and structural changes in coronary arteries. This review focuses on
      the technical background of CCTA-based quantitative plaque characterization.
      Furthermore, we discuss the available evidence for CCTA-based plaque
      characterization and the potential role of CCTA for risk stratification of
      patients with coronary artery disease. 

PMID- 25068027
TI  - Lipid profile in children with coronary artery disease in Sindh, Pakistan.
AB  - AIM: To evaluate lipid profile in children with coronary artery disease (CAD) in
      Hyderabad, Sindh, Pakistan. METHODS: The study included 100 children (6-15
      years), of which 43 were children of young parents (one or both) with recognized
      CAD, while the other 57 were children with no evidence of CAD (controls). All
      were evaluated for fasting blood lipid profile. Blood samples were collected from
      patients with CAD and healthy controls and analysis of the levels of lipid
      profile were carried out using a kit method on Microlab 300. RESULTS: Children
      with CAD had significantly higher levels of total serum cholesterol and
      triglycerides and decreased levels of high density lipoprotein and low density
      lipoprotein compared to children in the control group. Systolic and diastolic
      blood pressures were significantly higher, without any significant difference.
      CONCLUSION: CAD risk factors are significant regarding abnormal lipid levels.
      Genetic tendency seems to be important in the development of CAD in children.

PMID- 25068028
TI  - Is cardiac MRI an effective test for arrhythmogenic right ventricular
      cardiomyopathy diagnosis?
AB  - AIM: To evaluate the referrals with suspected arrhythmogenic right ventricular
      cardiomyopathy (ARVC) and compare cardiac MR (cMR) findings against clinical
      diagnosis. METHODS: A retrospective analysis of 114 (age range 16 to 83, males
      55% and females 45%) patients referred for cMR with a suspected diagnosis of ARVC
      between May 2006 and February 2010 was performed after obtaining institutional
      approval for service evaluation. Reasons for referral including clinical symptoms
      and family history of sudden death, electrocardiogram and echo abnormalities, cMR
      findings, final clinical diagnosis and information about clinical management were
      obtained. The results of cMR were classified as major, minor, non-specific or
      negative depending on both functional and tissue characterisation and the cMR
      results were compared against the final clinical diagnosis. RESULTS: The most
      common reasons for referral included arrhythmias (30%) and a family history of
      sudden death (20%). Of the total cohort of 114 patients: 4 patients (4%) had
      major cMR findings for ARVC, 13 patients (11%) had minor cMR findings, 2 patients
      had non-specific cMR findings relating to the right ventricle and 95 patients had
      a negative cMR. Of the 4 patients who had major cMR findings, 3 (75%) had a
      positive clinical diagnosis. In contrast, of the 13 patients who had minor cMR
      findings, only 2 (15%) had a positive clinical diagnosis. Out of the 95 negative
      patients, clinical details were available for 81 patients and none of them had
      ARVC. Excluding the 14 patients with no clinical data and final diagnosis, the
      sensitivity of the test was 100%, specificity 87%, positive predictive value 29%
      and the negative predictive value 100%. CONCLUSION: CMR is a useful tool for ARVC
      evaluation because of the high negative predictive value as the outcome has a
      significant impact on the clinical decision-making.

PMID- 25068029
TI  - Rare case of coronary to pulmonary vein fistula with coronary steal phenomenon.
AB  - Coronary artery fistulas are abnormal connections between coronary artery
      territories and cardiac chambers or major vessels, most of them are congenital.
      Patients with coronary artery fistula can be asymptomatic or present with
      different symptoms like angina. Cardiac computed tomography (CT) is one of the
      best modalities for diagnosis. We present an elderly patient that presented with
      angina symptoms, non invasive stress test was positive for ischemic heart
      disease, coronary angiogram could not reveal any obstructive lesions, but an
      abnormal branch of the left descending coronary artery (LAD), cardiac CT showed
      fistula that connect left anterior descending coronary artery to left superior
      pulmonary vein. Our case is extremely rare as most of the reported cases were
      fistulas between LAD and pulmonary artery, but in our case the fistula between
      LAD and left superior pulmonary vein. In addition, our patients' symptoms
      resolved with anti-ischemic medical treatment without any surgical intervention. 

PMID- 25068030
TI  - Worsening of coronary spasm during the perioperative period: A case report.
AB  - We present the case of a 65-year-old male with vasospastic angina (VSA) whose
      condition worsened during the perioperative period. He had been diagnosed with
      VSA 10 years prior. He was treated with two types of vasodilators and had not
      experienced any chest symptoms for 5 years. At this juncture, he underwent
      surgery for relapsed maxillary sublingual carcinoma. He had taken two
      vasodilators one day prior to surgery. Intravenous infusion of nitroglycerin
      (NTG) was initiated immediately before the surgery and continued the following
      day. Instead of stopping NTG, a dermal isosorbide dinitrate tape was applied on
      post-operative day 1. Two days later, a complete atrioventricular block with
      pulseless electrical activity appeared. After cardiopulmonary resuscitation,
      emergent coronary angiography showed severe coronary spasm in both the left and
      right coronary arteries. Intracoronary infusion of nitroglycerin and epinephrine
      with percutaneous cardiopulmonary support relieved the coronary spasm. During the
      perioperative period, several factors can trigger coronary vasospasm, including
      the discontinuation of vasodilators. Thus, surgeons, anesthetists, and
      cardiologists should watch for coronary vasospasm during this period and for
      worsening coronary spasm when discontinuing vasodilators in patients at risk for
      VSA. 

PMID- 25068031
TI  - 3D-echo in preoperative assessment of aortic cusps effective height.
AB  - Effective height, which represents the height difference between the central free
      margins and the aortic insertion lines can be easily determined by 2-D
      echocardiography and allows for identification of prolapse in the native cusps
      and assessment of prolapse correction after valve repair. Nonetheless, it allows
      to see only two of three aortic valve (AV) coaptation planes and this may lead to
      misunderstanding of the underlying pathophysiological mechanism for aortic
      regurgitation and hence in unsuccessful repair. In contrast, 3D transoesophageal
      echocardiography and multiple plane reconstruction lets visualize all the three
      coaptation planes between the AV cusps and it represents an invaluable tool in
      the assessment of aortic valve geometry. It is highly recommendable before AV
      repair to accurately study the complex three dimensional cusps anatomy and their
      geometric interrelation with aortic root. 

PMID- 25068032
TI  - Serotonin transporter genotype modulates HPA axis output during stress: effect of
      stress, dexamethasone test and ACTH challenge.
AB  - BACKGROUND: Studies show that the hypothalamic-pituitary-adrenal (HPA) axis is
      dysregulated in depression. Some studies suggest that variation in the serotonin
      transporter genotype (hereafter 5HTT) modulates both risk for depression and
      psychopathological HPA axis responsiveness. Rhesus monkeys are well suited to
      model such relationships. Rhesus macaque models of human psychopathology have
      assessed the effect of the serotonin transporter (rh5HTT) on levels of cortisol
      in stressed subjects. These studies show that that under conditions of stress,
      heterozygous females (Ls) reared under adversity exhibit high levels of cortisol.
      Studies have not to our knowledge, however, assessed the potential additive
      effect on the cortisol response in a number of macaque subjects homozygous for
      the serotonin transporter short allele (ss). Moreover, little is known about the
      level of the central or peripheral nervous system at which the 5HTT genotype acts
      to modulate the cortisol response. METHODS: This study assesses a relatively
      large number of subjects homozygous and heterozygous for the rh5HTT short and
      long alleles (a) during stress; (b) following a dexamethasone suppression test;
      and (c) following an adrenocorticotropic hormone (ACTH) challenge. Subjects
      included 190 infant rhesus macaques (Macaca mulatta - 84 males and 106 females;
      118 LL, 60 Ls, and 12 ss subjects), obtaining two blood plasma samples during the
      stress of separation from their mothers. Then on the following day, we obtained a
      blood sample following a dexamethasone test, and later that day we obtained a
      blood sample after an ACTH challenge test. Subjects ranged in age between 90 and
      128 days, with a mean age of 107 days. RESULTS: Subjects homozygous for the short
      allele had significantly higher levels of cortisol across all test conditions,
      when compared to those homozygous for the long allele, or those heterozygous with
      Ls alleles. Subsequent analyses showed a high correlation between individual
      cortisol levels across the three different tests. CONCLUSIONS: These data suggest
      that subjects homozygous for the short allele are more likely to show
      dysregulated cortisol levels in response to stress. Given the correlation in
      individual responses of the HPA axis across the different tests, our data suggest
      that the effect of the 5HTT genotype shows some commonality in its regulation of
      stress, feedback, and ACTH-stimulated cortisol output. Our data suggest that
      under conditions of stress, the serotonin transporter may modulate HPA axis
      psychopathology.

PMID- 25068033
TI  - Design, Synthesis, and Evaluation of 4- and 5-Substituted o
      (Octanesulfonamido)benzoic Acids as Inhibitors of Glycerol-3-Phosphate
      Acyltransferase.
AB  - Despite a rising demand for anti-obesity therapeutics, few effective
      pharmacological options are clinically available that target the synthesis and
      accumulation of body fat. Moderate inhibition of mammalian glycerol-3-phosphate
      acyltransferase (GPAT) with 2-(alkanesulfonamido)benzoic acids has recently been
      described in vitro, accompanied by promising weight loss in vivo. In silico
      docking studies with 2-(octanesulfonamido)benzoic acid modeled into the active
      site of squash GPAT revealed an unoccupied volume lined with hydrophobic residues
      proximal to C-4 and C-5 of the benzoic acid ring. In an effort to produce more
      potent GPAT inhibitors, a series of 4- and 5-substituted analogs were designed,
      synthesized, and evaluated for inhibitory activity. In general, compounds
      containing hydrophobic substituents at the 4- and 5-positions, such as biphenyl
      and alkylphenyl hydrocarbons, exhibited an improved inhibitory activity against
      GPAT in vitro. The most active compound, 4-([1,1'-biphenyl]-4-carbonyl)-2
      (octanesulfonamido)benzoic acid, demonstrated an IC50 of 8.5 uM and represents
      the best GPAT inhibitor discovered to date. Conversely, further substitution with
      hydroxyl or fluoro groups, led to a 3-fold decrease in activity. These results
      are consistent with the presence of a hydrophobic pocket and may support the
      binding model as a potential tool for developing more potent inhibitors.

PMID- 25068034
TI  - Recognition of diazirine-modified O-GlcNAc by human O-GlcNAcase.
AB  - The mammalian O-GlcNAc hydrolase (OGA) removes O-GlcNAc from serine and threonine
      residues on intracellular glycoproteins. OGA activity is sensitive to N-acyl
      substitutions to O-GlcNAc, with alkyl diazirine-modified O-GlcNAc (O-GlcNDAz)
      being completely resistant to removal by OGA. Using homology modeling, we
      identified OGA residues proximal to the N-acyl position of O-GlcNAc substrate.
      Mutation of one of these residues, C215, results in mutant enzymes that are able
      to hydrolytically remove O-GlcNDAz from a model compound. Further, the C215A
      mutant is capable of removing O-GlcNDAz from a peptide substrate. These results
      can be used to improve metabolism of O-GlcNAc analogs in cells. In addition, the
      enzyme specificity studies reported here provide new insight into the active site
      of OGA, an important drug target.

PMID- 25068035
TI  - The Software Ontology (SWO): a resource for reproducibility in biomedical data
      analysis, curation and digital preservation.
AB  - MOTIVATION: Biomedical ontologists to date have concentrated on ontological
      descriptions of biomedical entities such as gene products and their attributes,
      phenotypes and so on. Recently, effort has diversified to descriptions of the
      laboratory investigations by which these entities were produced. However, much
      biological insight is gained from the analysis of the data produced from these
      investigations, and there is a lack of adequate descriptions of the wide range of
      software that are central to bioinformatics. We need to describe how data are
      analyzed for discovery, audit trails, provenance and reproducibility. RESULTS:
      The Software Ontology (SWO) is a description of software used to store, manage
      and analyze data. Input to the SWO has come from beyond the life sciences, but
      its main focus is the life sciences. We used agile techniques to gather input for
      the SWO and keep engagement with our users. The result is an ontology that meets
      the needs of a broad range of users by describing software, its information
      processing tasks, data inputs and outputs, data formats versions and so on.
      Recently, the SWO has incorporated EDAM, a vocabulary for describing data and
      related concepts in bioinformatics. The SWO is currently being used to describe
      software used in multiple biomedical applications. CONCLUSION: The SWO is another
      element of the biomedical ontology landscape that is necessary for the
      description of biomedical entities and how they were discovered. An ontology of
      software used to analyze data produced by investigations in the life sciences can
      be made in such a way that it covers the important features requested and
      prioritized by its users. The SWO thus fits into the landscape of biomedical
      ontologies and is produced using techniques designed to keep it in line with
      user's needs. AVAILABILITY: The Software Ontology is available under an Apache
      2.0 license at http://theswo.sourceforge.net/; the Software Ontology blog can be
      read at http://softwareontology.wordpress.com.

PMID- 25068036
TI  - Tools to identify linear combination of prognostic factors which maximizes area
      under receiver operator curve.
AB  - BACKGROUND: The linear combination of variables is an attractive method in many
      medical analyses targeting a score to classify patients. In the case of ROC
      curves the most popular problem is to identify the linear combination which
      maximizes area under curve (AUC). This problem is complete closed when normality
      assumptions are met. With no assumption of normality search algorithm are avoided
      because it is accepted that we have to evaluate AUC n(d) times where n is the
      number of distinct observation and d is the number of variables. METHODS: For d =
      2, using particularities of AUC formula, we described an algorithm which lowered
      the number of evaluations of AUC from n(2) to n(n-1) + 1. For d > 2 our proposed
      solution is an approximate method by considering equidistant points on the unit
      sphere in R(d) where we evaluate AUC. RESULTS: The algorithms were applied to
      data from our lab to predict response of treatment by a set of molecular markers
      in cervical cancers patients. In order to evaluate the strength of our algorithms
      a simulation was added. CONCLUSIONS: In the case of no normality presented
      algorithms are feasible. For many variables computation time could be increased
      but acceptable.

PMID- 25068037
TI  - The Role of Visual Stimuli in Cross-Modal Stroop Interference.
AB  - It has long been known that naming the color of a color word leads to what is
      known as the Stroop effect (Stroop, 1935). In the traditional Stroop task, when
      compared to naming the color of a color-neutral stimulus (e.g. an X or color
      patch), the presence of an incongruent color word decreases performance (Stroop
      interference), and a congruent color word increases performance (Stroop
      facilitation). Research has also shown that auditory color words can impact the
      color naming performance of colored items in a similar way in a variation known
      as cross-modal Stroop (Cowan & Barron, 1987). However, whether the item that is
      colored interacts with the auditory distractor to affect cross-modal Stroop
      interference is unclear. Research with the traditional, visual Stroop task has
      suggested that the amount of color the visual item displays and the semantic and
      phonetic components of the colored word can affect the magnitude of the resulting
      Stroop interference; as such, it is possible the same components could play a
      role in cross-modal Stroop interference. We conducted two experiments to examine
      the impact of the composition of the colored visual item on cross-modal Stroop
      interference. However, across two different experiments, three test versions, and
      numerous sets of trials, we were only able to find a small effect of the visual
      stimulus. This finding suggests that while the impact of the auditory stimuli is
      consistent and robust, the influence of non-word visual stimuli is quite small
      and unreliable and, while occasionally being statistically significant, it is not
      practically so.

PMID- 25068038
TI  - Adsorption of Proteins to Thin-Films of PDMS and Its Effect on the Adhesion of
      Human Endothelial Cells.
AB  - This paper describes a simple and inexpensive procedure to produce thin-films of
      poly(dimethylsiloxane). Such films were characterized by a variety of techniques
      (ellipsometry, nuclear magnetic resonance, atomic force microscopy, and
      goniometry) and used to investigate the adsorption kinetics of three model
      proteins (fibrinogen, collagen type-I, and bovine serum albumin) under different
      conditions. The information collected from the protein adsorption studies was
      then used to investigate the adhesion of human dermal microvascular endothelial
      cells. The results of these studies suggest that these films can be used to model
      the surface properties of microdevices fabricated with commercial PDMS. Moreover,
      the paper provides guidelines to efficiently attach cells in BioMEMS devices.

PMID- 25068039
TI  - Biological removing of Cadmium from contaminated media by fungal biomass of
      Trichoderma species.
AB  - BACKGROUND: Environment pollution by heavy metals is a global disaster and there
      are several cleaning methods including bioremediation. Trichoderma species
      inhibit the growth of pathogenic fungi and play a useful role in agriculture and
      ecosystem management. METHODS: In this study, the removing of cadmium ions by
      three species of Trichoderma (T. asperellum, T. harzianum and T. tomentosum) were
      studied under different pH (5, 7, 9) and different concentrations of Cd (1, 100,
      200 ppm) in liquid media containing potato extract and dextrose. Above mentioned
      fungal strains were cultured in the Cd-polluted media and the remaining amount of
      metal ions in the media was measured after two months growth, using atomic
      absorption. RESULTS: Results showed that all three fungal species were able to
      reduce the amount of Cd in the all three pH of the medias; but their removal
      ability varies depending on the species and cultural conditions. T. asperellum
      was showed maximum removal efficiency of cadmium (76.17%), (10.75 mg/g, at fungal
      dry weight). Based on our results, the most removal efficiency of Cd ions for the
      fungal species was evaluated in the alkaline pH. CONCLUSIONS: Trichoderma species
      are important fungi in decreasing of Cadmium ions. They have bioremediation
      potency under various pH and concentration conditions.

PMID- 25068040
TI  - In vitro evaluation of antioxidant properties of ten Iranian medicinal plants.

PMID- 25068041
TI  - A Systematic Review and Meta-Analysis Study to Investigate the Prevalence of
      Helicobacter pylori and the Sensitivity of its Diagnostic Methods in Iran.
AB  - CONTEXT: Helicobacter pylori is the most common infecting organism affecting
      humans, being almost half the population infected. The aim of this study was to
      find out the epidemiological features and the sensitivity of diagnostic methods
      of Helicobacter pylori infection in Iran, which can provide the logic of
      developing preventive approaches to control Helicobacter pylori infections and
      the associated diseases. EVIDENCE ACQUISITION: By reviewing the databases of SID,
      MAGIRAN, SCOPUS, MEDLIB, Google, ISI and PUBMED, a total of 30 papers, published
      from 1994 to 2011, were extracted. Summary prevalence and 95% confidence
      intervals (95% CI) were calculated using random-effects model. Statistical
      analyses were performed using STATA Ver.11. RESULTS: Among the 30 studies
      evaluated, the prevalence rate of Helicobacter pylori infections in Iran was
      estimated as 50.7 % (95% CI: 44.4-56.9%). When the sensitivity of diagnostic
      methods was evaluated, ELISA, with an accuracy rate of 52.3% (95% CI: 43.8 to
      60.8%) was found the most accurate diagnostic method available. The highest and
      the least Helicobacter pylori prevalence were 19.2% in Tehran and 74.27% in
      Mazandran respectively. CONCLUSIONS: About half the population in Iran is
      infected with Helicobacter pylori, the pollution in different areas and
      preventive strategies should be carried out to control this infection. The
      prevalence rate of Helicobacter pylori infections in Iran showed only little
      changes during the years 1994 to 2011.

PMID- 25068042
TI  - Successful treatment of pemphigus vulgaris with the extensive mucocutaneous
      lesions in an elderly patient.
AB  - INTRODUCTION: Pemphigus vulgaris (PV) is a chronic and infrequent autoimmune
      mucocutaneous disease that is characterized by the loose blisters and erosions on
      the skin and mucous membrane. Middle-aged adults are affect most frequently and
      the elderly and juvenile cases are infrequent. Herein, we reported a case of
      pemphigus vulgaris in an elderly patient. CASE PRESENTATION: We reported a case
      of pemphigus vulgaris in a 79-year-old patient with the extensive mucocutaneous
      lesions. We also reviewed the literature in MEDLINE with keywords such as
      pemphigus vulgaris, elderly, mucocutaneous lesions, oral lesions, and treatment.
      DISCUSSION: We have to stress that the importance of this case report is its
      presentation in an elderly patient, as the frequent age of presentation in the
      Iranian patients is the middle age. On the other hand, PV occurs rarely, thus,
      the reporting of any rare case with some exceptions is important.

PMID- 25068043
TI  - Types of nasal delivery drugs and medications in Iranian traditional medicine to
      treatment of headache.
AB  - CONTEXT: Headache is a common symptom throughout the world. The main purpose of
      patient-centered approaches is the utilization of useful and simple treatment.
      Nowadays, there is a rising propensity toward herbal remedies. Nasal route is one
      of the ancient and topical prescriptions used in headache. In Iranian traditional
      medicine, physicians such as Avicenna were prescribing herbal drugs through the
      nose to treat a variety of central nervous system diseases like headache. In this
      review paper, authors have attempted to introduce different types of nasal
      administrations which were used in Iranian traditional medicine for the treatment
      of headaches. EVIDENCE ACQUISITION: Initially, we studied two different types of
      Canon and separated all herbs used in the treatment of headache. Next, all plants
      were classified according to the method of prescription. Then, we pick out all
      the plants which were nasally utilized in the treatment of headache and divided
      them based on the method of administration. In order to find scientific names of
      herbs, we used two different botany references. Moreover, we conducted various
      researches in scientific databases with the aim of finding results concerning the
      analgesic and antinociceptive effects of herbs. Throughout the research, key
      terms were "analgesic" and "antinociceptive "with the scientific names of all
      herbs separately. The databases searched included PubMed, Scopus, Cochrane
      library and SID. RESULTS: 35 plants were prescribed for the treatment of
      headaches, which were all nasally used. These plants took either the form of
      powder, liquid or gas (steam). They were divided in to six categories according
      to the method of prescription. The Percentage of usage for each method was as
      follows: 62% Saoot (nasal drop), 25% Shamoom (smell), 17% Inkabab (vapor), 11%
      Nafookh (snuff), 11% Nashooq (inhaling) and 2% Bokhoor (smoke). CONCLUSIONS:
      Medications that are used via nasal delivery have greater effect than oral
      medications. Iranian physicians were fully aware of systemic effects of topical
      medications, including prescription drugs through the nose. The study of ancient
      medical texts helps us in identification of herbal medicine and the investigation
      of new way for the preparation of drugs.

PMID- 25068044
TI  - Effects of gallic Acid and cyclosporine a on antioxidant capacity and cardiac
      markers of rat isolated heart after ischemia/reperfusion.
AB  - BACKGROUND: Myocardial infarction is one of the important causes of death during
      old ages. Gallic acid as an antioxidant or cyclosporine A (CsA) as inhibitor of
      mitochondrial permeability transition pore (mPTP) alone could prevent these
      complications to some extent, but their combination effect has not been
      investigated. OBJECTIVES: The aim of this study was to determine the combined
      effect of gallic acid and CsA on antioxidant capacity of isolated heart tissues
      during ischemia reperfusion. MATERIALS AND METHODS: EIGHTY MALE WISTAR RATS WERE
      RANDOMLY ASSIGNED TO DIFFERENT GROUPS: sham, control (Ca, received saline, 1
      mL/kg); 3 groups were pretreated with gallic acid (G1a: 7.5, G2a: 15, G3a: 30
      mg/kg) for 10 days, and the other 3 groups were pretreated with gallic acid and
      received CsA (0.2 uM) for 10 minutes before induction of ischemia and during the
      first 10 minutes of reperfusion (G1b, G2b and G3b) and the last group received
      CsA alone (Cb). After 10 days of pretreatment, the heart was isolated and
      transferred to the Langendorff apparatus and exposed to 30 minutes ischemia
      followed by 60 minutes of reperfusion. After that cardiac markers and antioxidant
      enzymes were assessed in cardiac tissues. RESULTS: Lactate dehydrogenase (LDH),
      Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)
      activity increased and malondialdehyde (MDA) decreased in animals pretreated with
      gallic acid significantly. However, pretreatment with gallic acid followed by CsA
      during reperfusion improved the antioxidant capacity and cardiac marker enzymes
      and restored the lipid peroxidation more effective than gallic acid or CsA alone.
      Nevertheless, CsA did not change the cardiac marker enzymes significantly.
      CONCLUSIONS: Gallic acid and CsA combination improved antioxidant capacity and
      cell membrane integrity more than each one alone. Therefore, it can be a
      therapeutic approach to reduce the I/R injury.

PMID- 25068045
TI  - Effect of combination exercise therapy on walking distance, postural balance,
      fatigue and quality of life in multiple sclerosis patients: a clinical trial
      study.
AB  - BACKGROUND: Multiple Sclerosis (MS) is a demyelinating disease of the nervous
      system which has numerous disabling effects on patients. OBJECTIVES: This study
      aimed at investigating the short- and long-term effects of a period of
      combination exercise therapy on walking distance, balance, fatigue and quality of
      life in multiple sclerosis patients referred to the physiotherapy clinic of
      Iran's Multiple Sclerosis Society in 2013. PATIENTS AND METHODS: This study was a
      randomized controlled clinical trial on 59 patients divided into the intervention
      (n = 39) and control groups (n = 20). The intervention group received 10 weeks of
      combination therapy including aerobic, strengthening, balancing and stretching
      exercises. A week before, a week later and a year after the beginning of the
      exercises, both groups of patients received BBSS, six minute walking, Family
      Support Services (FSS), Expanded Disability Status Scale (EDSS) and quality of
      life tests. The scores of two groups were then compared using statistical tests
      such as repeated measures ANOVA test. RESULTS: THE RESULTS INDICATED SIGNIFICANT
      CHANGES IN THE INTERVENTION GROUP IN COMPARISON TO THE CONTROL GROUP IN THE
      SECOND PHASE OF THE STUDY COMPARING TO THE FIRST ONE FOR ALL TESTS EXCEPT EDSS
      (MEAN DIFFERENCE SCORES OF EDSS: -0.13), P-value = 0.60; FSS: -6.9, P-value =
      0.02, Mental Quality of Life (QOL): 16.36, P-value = 0.001; Physical QOL: 12.17,
      P-value = 0.001, six minute walking: 137.2, P-value < 0.0001; and Berg: 3.34, P
      value < 0.0001. These changes were not significant in the second phase of the
      study comparing to the third one; however, they were again significant in the
      third phase comparing to the first phase of the study (P < 0.05). CONCLUSIONS:
      Exercise has significant effect on improving symptoms of multiple sclerosis, and
      cessation of exercise may cause recurrence of symptoms in the intervention group
      with a slope similar to that of the control group. Therefore, continuous rather
      than short period exercises have valuable symptomatic and supportive relief
      effects in patients.

PMID- 25068046
TI  - Preoperative evaluation of risk of ovarian malignancy algorithm index in
      prediction of malignancy of adnexal masses.
AB  - BACKGROUND: Differentiation between benign and malignant ovarian neoplasms is
      essential to create a system for patient referrals. OBJECTIVES: The aim of the
      present prospective trial was to analyze the value of the risk of ovarian
      malignancy algorithm (ROMA) in prediction of adnexal masses malignancy in pre-
      and post-menopause women before operation. MATERIALS AND METHODS: Preoperative
      serum samples were tested for CA125 and HE4 using fully automated methods (Abbott
      architect) and gained best cutoff. The ROMA index was analyzed in 99 patients
      (including 68 pre-menopause and 31 menopause) with adnexal masses referred to
      Imam Hossein Hospital/Tehran/Iran and had been scheduled for operation. The
      pathological results showed 43 cases (22 menopause) with malignant adnexal masses
      and 56 cases (9 menopauses) with benign adnexal masses. Demographical data,
      clinical symptoms and the ROMA index were separately analyzed and contrasted in
      benign and malignant in both menopause and pre-menopause patients. RESULTS: The
      only significant difference was the older age of the malignant group vs. benign
      group (P = 0.001) regarding demographic findings. As concerns the clinical
      symptoms, presence of abdominal discomfort in pre-diagnosis period was the only
      significant parameter in malignant group (P = 0.001). Additionally, data analysis
      of patients as a total group showed that specificity (96.4%), positive predictive
      value (PPV) (94.1%), area under the curve (AUC) (0.907), and diagnostic accuracy
      (DA) (86.9%) of the ROMA were higher than HE4 (91.1%, 85.7%, 0.857 and 81.8%.
      respectively) and CA125 (87.9%, 67.3%, 0.828 and 75.8%, respectively) alone.
      Besides, negative predictive value (NPV) (86.4%) and sensitivity (86.1%) of CA125
      were higher than HE4 (79.7% and 69.8%, respectively). In contrast, specificity of
      HE4 (91.1%) was higher than CA125 (67.9%). Data analysis of patients as two
      groups (pre and post menopause groups) showed the same results. CONCLUSIONS:
      Specificity, DA and AUC of the ROMA were higher than HE4 and CA125 taken
      separately.

PMID- 25068047
TI  - Air travel considerations for the patients with heart failure.
AB  - CONTEXT: Prevalence of patients with heart failure (HF) is increasing in
      worldwide, and also the number of people with HF traveling long distances is
      increasing. These patients are more prone to experience problems contributed air
      travel and needs more attention during flight. However, observational studies
      about problems of HF patients during flight and appropriated considerations for
      them are limited. EVIDENCE ACQUISITION: We evaluated the conditions that may be
      encountered in a HF patient and provide the recommendations to prevent the
      exacerbation of cardiac failure during air travel. For this review article, a
      comprehensive search was undertaken for the studies that evaluated the
      complications and considerations of HF patients during flight. Data bases
      searched were: MEDLINE, EMBASE, Science Direct, and Google Scholar. RESULTS: HF
      patients are more prone to experience respiratory distress, anxiety, stress,
      cardiac decompensation, and venous thromboembolism (VTE) during air travel.
      Although stable HF patients can tolerate air travel, but those with acute heart
      failure syndrome should not fly until complete improvement is achieved.
      CONCLUSIONS: Thus, identifying the HF patients before the flight and providing
      them proper education about the events that may occur during flight is necessary.

PMID- 25068048
TI  - Socioeconomic inequality and its determinants regarding infant mortality in iran.
AB  - BACKGROUND: Infant mortality rate is a useful indicator of health conditions in
      the society, the racial and socioeconomic inequality of which is from the most
      important measures of social inequality. OBJECTIVES: The aim of this study was to
      determine the socioeconomic inequality and its determinants regarding infant
      mortality in an Iranian population. PATIENTS AND METHODS: This cross-sectional
      study was performed on 3794 children born during 2010-2011 in Shahroud, Iran.
      Based on children's addresses and phone numbers, 3412 were available and finally
      3297 participated in the study. A data collection form was filled out through
      interviewing the mothers as well as using health records. Using principal
      component analysis, the study population was divided to high and low
      socioeconomic groups based on the case's home asset, education and job of the
      household's head, marital status, and composition of the household members.
      Inequality between the groups with regard to infant mortality was investigated by
      Blinder-Oaxaca decomposition method. RESULTS: The mortality rate was 15.1 per
      1000 live births in the high socioeconomic group and 42.3 per 1000 in the low
      socioeconomic group. Mother's education, consanguinity of parents, and infant's
      nutrition type and birth weight constituted 44% of the gap contributing factors.
      Child's gender, high-risk pregnancy, and living area had no impact on the gap.
      CONCLUSIONS: There was considerable socioeconomic inequality regarding infant
      mortality in Shahroud. Mother's education was the most contributing factor in
      this inequality.

PMID- 25068049
TI  - The effects of body position on chemotherapy-induced nausea and vomiting: a
      single-blind randomized controlled trial.
AB  - BACKGROUND: Chemotherapy is the cornerstone of cancer treatment; however,
      alongside therapeutic effects, nausea and vomiting are two common complications
      of chemotherapy. OBJECTIVES: The aim of this study was to investigate the effects
      of body position on chemotherapy-induced nausea and vomiting. MATERIALS AND
      METHODS: This was a single-blind randomized controlled clinical trial. We
      recruited a convenience sample of 79 patients and randomly allocated them to
      either experimental or control groups. Patients in the control group received
      chemotherapy in supine position while the experimental group received
      chemotherapy in semi-Fowler's position. All patients were assessed for the
      severity, duration, and frequency of nausea and vomiting episodes every three
      hours up to 24 hours, ie, in nine time-points. Study data was analyzed by SPSS v.
      16. RESULTS: The severity, duration, and frequency of nausea and the severity and
      frequency of vomiting episodes in the control group differed significantly across
      the nine measurement time-points (P < 0.001). In the experimental group, the
      severity (P = 0.254) and frequency of nausea (P = 0.002) episodes as well as the
      frequency of vomiting (P = 0.008) episodes differed significantly across the
      measurement time-points. Moreover, the study groups differed significantly across
      the measurement time-point in terms of the severity (P < 0.001), duration (P <
      0.001), and frequency of nausea (P = 0.002) and the severity (P < 0.001) and
      frequency (P < 0.001) of vomiting episodes. CONCLUSIONS: Compared to supine
      position, semi-Fowler's position is more effective in relieving chemotherapy
      induced nausea and vomiting.

PMID- 25068051
TI  - A framework of a health system responsiveness assessment information system for
      iran.
AB  - BACKGROUND: Responsiveness assessment of health system with the quality
      information is the key in effective evidence-based management of the health
      system. OBJECTIVES: This qualitative study defines the necessary components
      required for the health system responsiveness assessment information system (HS
      RAIS). MATERIALS AND METHODS: This study was conducted based on mixed-methods
      approach and by using Delphi technique (29 participants in first round and 25
      participants in second round) and semi-structured interviews in Iran 2013. The
      participant selection strikes a balance between being able to provide valid data,
      and increasing representative's leverage. The final framework for HS-RAIS was
      extracted from in-depth interviews with ten key informants. RESULTS: We followed
      these recommendations and developed a framework in 10 components including:
      minimum datasets, data sources, data gathering, data analysis, feedback and
      dissemination, legislative needs, objectives of health system responsiveness
      assessment, repetition period, executive committee and stewardship. CONCLUSIONS:
      This framework provides useful information for decision-making at all levels
      about assessment of health system.

PMID- 25068050
TI  - Coping work strategies and job satisfaction among Iranian nurses.
AB  - CONTEXT: Nursing is a stressful job that could create physical and psychological
      disorders. Many studies presented information on stress, effects of coping
      strategies, and job satisfaction of nurses within health setting. We aimed to
      identify and describe nursing stresses, coping strategies and job satisfaction of
      Iranian nurses who are working or worked in different wards. EVIDENCE
      ACQUISITION: In this review, we studied peer-reviewed journal articles on the
      field of stress, coping strategies and job satisfaction in nursing practice,
      especially Iranian nurses, which were published between 2000 and 2013. In this
      regard, we searched databases of PubMed, Elsevier, Google, BMJ, PMC, and MEDLINE.
      RESULTS: The majority of the studies (60%) had analyzed the effect of coping
      strategies, experiences and perception of job-related stresses in Iranian nurses
      working in hospitals. In some of the reviewed studies (60%), the majority of the
      samples enrolled Iranian nurses. Forty percent of studies selected a maximum
      sample size of 565 (44%) participants in 2011. Nursing stress scale employed at
      30% of the studies was the most commonly used strategy. This reviewed studies
      also revealed a combined measurement (60% of studies), based on categorical
      stress measurement, effects of coping strategies, and job satisfaction methods.
      Three studies explored the relationship between job stress and job satisfaction.
      For instance, the majority (74.4%) of nurses reported job satisfaction.
      CONCLUSIONS: Effect of coping strategies and job satisfaction on Iranian nurses
      is a well-accepted issue and has important positive outcomes on several areas of
      health discipline.

PMID- 25068052
TI  - Long-term neurodevelopmental outcomes after preterm birth.
AB  - CONTEXT: All over the the world, preterm birth is a major cause of death and
      important neurodevelopmental disorders. Approximately 9.6% (12.9 million) births
      worldwide are preterm. EVIDENCE ACQUISITION: In this review, databases such as
      PubMed, EMBASE, ISI, Scopus, Google Scholar and Iranian databases including
      Iranmedex, and SID were researched to review relevant literature. A comprehensive
      search was performed using combinations of various keywords. RESULTS: Cerebral
      palsy especially spastic diplegia, intellectual disability, visual (retinopathy
      of prematurity) and hearing impairments are the main neurodevelopmental disorders
      associated with prematurity. CONCLUSIONS: The increased survival of preterm
      infants was not associated with lower complications. There is now increasing
      evidence of sustained adverse outcomes into school age and adolescence, for
      preterm infants.

PMID- 25068053
TI  - Alendronate Effect on the Prevention of Bone loss in Early Stages of Ankylosing
      Spondylitis: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease that
      leads to a progressive ankylosis of vertebras and ossification of paravertebral
      ligaments. Bone loss and osteoporosis are amongst the important complications of
      AS, treatment of which is a challenging issue. OBJECTIVES: This study aimed to
      clarify the effect of alendronate on the prevention of bone loss in patients with
      early AS. PATIENTS AND METHODS: In a randomized, double-blind, placebo-controlled
      study, 24 patients with early stages of AS were recruited in Emam Reza Hospital,
      Tabriz University of Medical Sciences. The diagnostic criteria of early AS were
      Schober's index >= 5, normal hip joint in pelvic radiography, and absence or
      rarity of syndesmophytes in spine radiography (Taylor index <= 1). The
      participants were randomly allocated to the treatment and control groups and
      received 70 mg/week of alendronate and the same dose of placebo, respectively,
      for 12 months. Before and 12 months after the intervention, bone densitometry was
      performed from lumbar and pelvic region using the dual-energy X-ray
      absorptiometry (DEXA) method with Hologic QDR model instrument. Patients,
      physicians who prescribed the medications and those who interpreted the outcomes,
      and densitometry technicians were unaware of the assigned medication to each
      patient. Both groups received supplemental calcium (1000 mg/day) and vitamin D
      (400 mg/day). RESULTS: After 12 months of treatment, hip and lumbar bone mineral
      density differences were not statistically significant between study groups (P =
      0.061 and P = 0.112, respectively). No case of clinically apparent vertebral and
      nonvertebral fracture were observed in the treatment and control groups.
      CONCLUSIONS: Our results suggested that applying alendronate was ineffective in
      preventing bone loss in patients with early stages of AS.

PMID- 25068054
TI  - Effects of Vitamin D and Calcium Supplementation on Micro-architectural and
      Densitometric Changes of Rat Femur in a Microgravity Simulator Model.
AB  - BACKGROUND: Revealing data on the role of vitamin D and calcium supplementation
      in bone health has led some to suggest that vitamin D and calcium treatment could
      also play a role in protecting bone against microgravity-induced mineral loss.
      OBJECTIVES: The aim of the present study was to investigate the effects of
      vitamin D and calcium administration on microscopic and densitometric changes of
      rat femur in a Microgravity Simulator Model. MATERIALS AND METHODS: After
      designing a Microgravity Simulator Model, 14 rats were placed in the cages as
      follows: seven rats as osteoporosis group and seven rats received oral supplement
      of calcium/vitamin D as the treatment group. Animals were sacrificed after eight
      weeks and then both femurs were removed. Bone mineral density was measured for
      one femur from each animal, and morphologic studies were evaluated for the
      contralateral femur. RESULTS: Bone mineral density of the whole femur in the
      treatment group was significantly higher than the osteoporosis group (0.168 +/-
      0.005 vs. 0.153 +/- 0.006, P = 0.003). Also, bone mineral content of the whole
      femur was significantly higher in treatment group (0.415 +/- 0.016 vs. 0.372 +/-
      0.019, P = 0.003). However, resorption eroded surface percentage was higher in
      the osteoporosis group (18.86 +/- 3.71% vs. 9.71 +/- 1.61%, P = 0.002).
      CONCLUSIONS: According to the results of this study, vitamin D and calcium
      administration might have protective effects against microgravity-induced mineral
      loss in a Rat Microgravity Simulator Model.

PMID- 25068055
TI  - Hydroxyurea Treatment in Transfusion-Dependent beta-Thalassemia Patients.
AB  - BACKGROUND: beta-Thalassemia is an inherited hemoglobin disorder caused by
      defective synthesis of beta-globin chains. Hemoglobin (Hb) F induction is a
      possible therapeutic approach which can partially compensate for alpha and non
      alpha globin chains imbalance. OBJECTIVES: We aimed to investigate the efficacy
      and safety of Hydroxyurea (HU) in diminishing transfusion requirements of
      patients with beta-thalassemia major in Southern Iran. PATIENTS AND METHODS: In
      this single-arm clinical trial, all transfusion-dependent beta-thalassemia
      patients older than two years old (n = 97) who had inclusion criteria of the
      study and had been registered for at least six months in Dastgheib thalassemia
      outpatient clinic (a referral center affiliated to Shiraz University of Medical
      Sciences) were evaluated from October 2010 to December 2011. The patients were
      treated with HU with a mean dose of 10.5 mg/kg for a mean duration of 8 months
      (range 3-14 months). Transfusion needs and Hb levels were compared before and
      after HU treatment. RESULTS: The mean volume of blood transfusion decreased
      significantly following HU treatment (0.71 mL/kg/day vs. 0.43 mL/kg/day, P <
      0.001). Two-thirds of the patients showed good and partial response. No serious
      adverse reaction was observed except persistent neutropenia in two patients.
      CONCLUSIONS: Hydroxyurea can be safely used in some transfusion-dependent beta
      thalassemia patients to decrease their transfusion needs.

PMID- 25068056
TI  - Cross-talk between endothelin-1 and mineral metabolism in hemodialysis patients:
      a cross-sectional study.
AB  - BACKGROUND: Endotheline-1 (ET-1), an endothelial mediator, influences on mineral
      metabolism; especially vascular calcification in uremic patients. OBJECTIVES: The
      aim of the present study was to evaluate of ET-1, high-sensitivity C-reactive
      protein (hs-CRP) and mineral metabolites as the main factors for vascular
      calcification and inflammation in hemodialysis (HD) patients. PATIENTS AND
      METHODS: In this cross-sectional study, 46 chronic stable HD patients were
      selected from nephrology departments of Tabriz University of Medical Sciences
      affiliated hospitals and classified based on phosphorus (P), Ca-P product (Ca *
      P) and intact Parathyroid Hormone (iPTH) levels. We evaluated fasting serum ET
      1and hs-CRP levels by the standard methods and compared with 46 healthy control
      subjects. RESULTS: The levels of serum hs-CRP and ET-1 were significantly higher
      in the patient's group compared with controls (4.40 +/- 1.26 vs. 1.38 +/- 1.61, P
      < 0.0001, and 2.31 +/- 0.87 vs. 0.75 +/- 0.48, P < 0.0001, respectively) and with
      regard to Ca * P product cut-off point (3.99 +/- 0.78 vs. 5.33 +/- 1.64, P <
      0.0001, and 2 +/- 0.73 vs. 3.04 +/- 0.73, P < 0.0001 respectively). ET-1 was
      correlated significantly with hs-CRP level (r = 0.776, P < 0.0001). Serum P, Ca *
      P and iPTH levels directly and Ca indirectly were correlated with serum ET-1 in
      HD patients (r = 0.932, P < 0.0001, r = 0.766, P < 0.0001, r = 0.514, P < 0.0001,
      r = -0.538, P < 0.0001 respectively). Multiple regression analysis demonstrated
      that serum P were independently associated with ET-1 levels (beta = 0.932, P <
      0.0001). CONCLUSIONS: Serum P and iPTH levels were independently associated with
      ET-1 and those may play a role in development of endothelial dysfunction in
      chronic kidney disease.

PMID- 25068057
TI  - Psychosocial complications of coronary artery disease.
AB  - BACKGROUND: Cardiovascular diseases are the leading causes of death around the
      world. The coronary artery disease (CAD) is one of the most common diseases in
      this category, which can be the trigger to various psychosocial complications. We
      believe that inadequate attention has been paid to this issue. OBJECTIVES: The
      purpose of the present study was to explore the psychosocial complications of CAD
      from the Iranian patients' perspective. PATIENTS AND METHODS: A qualitative
      design based on the content analysis approach was used to collect the data and
      analyze the perspective of 18 Iranian patients suffered from CAD, chosen by a
      purposeful sampling strategy. Semi-structured interviews were held in order to
      collect the data. Sampling was continued until the data saturation. The data were
      analyzed using qualitative content analysis approach by MAXQUDA 2010 software.
      RESULTS: This study revealed the theme of the patients' challenges with CAD. This
      theme consisted of: "primary challenges," including doubting early diagnosis and
      treatment, and feeling being different from others; "psychological issues,"
      including preoccupation, fear of death and surgical intervention, recurrence
      stress , anxiety and depression; "problems of life," including financial
      problems, work-related problems, and family-related problems; and "sociocultural
      issues," including change in perspective of people towards the patient, and
      cultural issues. CONCLUSIONS: Although the management of physical problems in
      patients with CAD is important, psychosocial effects of this disease is more
      important. Thus, health care personnel should pay ample attention to identify and
      resolve psychosocial problems of these patients. Results of this study can be
      used to empower these patients.

PMID- 25068058
TI  - Aromatherapy with citrus aurantium oil and anxiety during the first stage of
      labor.
AB  - BACKGROUND: Anxiety is the most common psychological response of women to labor.
      Aromatherapy, i.e. the use of fragrant essential oils to stimulate the olfactory
      system, can create a state of calmness and help to alleviate anxiety. OBJECTIVES:
      The present study tried to determine the efficacy of aromatherapy with Citrus
      aurantium oil in reducing anxiety during the first stage of labor. PATIENTS AND
      METHODS: This randomized clinical trial was conducted on two groups of pregnant
      women, referred to Vali-Asr Hospital (Tuyserkan, Iran) between June and September
      2013. The sample size was comprised of 63 subjects in each group. Gauzes
      impregnated with 4 mL of C. aurantium distillate and normal saline were attached
      to the collar of subjects in the aromatherapy and control groups, respectively.
      The gauzes were changed every 30 minutes. The levels of anxiety in both groups
      were measured at baseline and after the intervention at dilations of 3-4 and 6-8
      cm. The participants were followed up until delivery and the first- and fifth
      minute Apgar scores were recorded. Data were collected using a demographic and
      obstetric characteristics questionnaire, an examination and observation
      checklist, and Spielberger state-trait anxiety questionnaire. Data analysis was
      performed with independent-t, Mann-Whitney, and chi-square tests in SPSS-22. P
      values less than 0.05 were considered significant. RESULTS: Before the
      intervention, both groups had same levels of anxiety. However, the levels of
      anxiety at dilations of 3-4 and 6-8 cm were significantly lower in the
      aromatherapy group compared with the control group. CONCLUSIONS: The results of
      this study confirmed aromatherapy with C. aurantium blossom oil as a simple,
      inexpensive, noninvasive, and effective intervention to reduce anxiety during
      labor.

PMID- 25068059
TI  - Barriers to Middle-Aged Women's Mental Health: A Qualitative Study.
AB  - BACKGROUND: Middle-aged women encounter some barriers to their mental health,
      putting them at great risk for developing mental disorders. OBJECTIVES: The aim
      of this study was to explore barriers to middle-aged women's mental health.
      MATERIALS AND METHODS: This was a qualitative content analysis study conducted in
      2013 in Kashan, Iran. A purposive, maximum variation sample of 23 middle-aged
      women was recruited to the study. Data were collected by conducting semi
      structured individual interviews. We employed the conventional qualitative
      content analysis approach for data analysis. RESULTS: Barriers to middle-aged
      women's mental health fell into two main themes including 'increased life
      concerns' and 'physical and psychological tensions'. The two sub-categories of
      the first theme included having mental concerns and increased burden of roles.
      The second main theme also consisted of two categories including perceived
      undesirable physical changes and perceived undesirable psychological changes.
      CONCLUSIONS: Experiences of middle-aged women showed that culturally appropriate
      interventions to alleviate the concerns of life, physical and mental stress is
      essential to preserve stability of mental health.

PMID- 25068060
TI  - Comparing Nigella sativa Oil and Fish Oil in Treatment of Vitiligo.
AB  - BACKGROUND: Vitiligo is one of the autoimmune skin diseases that destroy the
      melanocytes of the skin. Moreover, its prevalence varies in different countries
      and regions. OBJECTIVES: The aim of this study was to compare the effect of
      Nigella sativa and fish oil on vitiligo lesions of the patients referred to a
      dermatology clinic. MATERIALS AND METHODS: This randomized, double blind clinical
      trial was conducted in the dermatology clinic of the Imam Khomeini Hospital
      Ahvaz, Iran, from June to December 2011. We used a randomized simple sampling.
      From 96 patients with vitiligo, 52 eligible patients were selected and allocated
      to two groups with equal size. The study medications were applied twice a day by
      patients on their lesions. After six months, the improvement rate of lesions was
      assessed by the Vitiligo Area Scoring Index (VASI). Data were analyzed using SPSS
      v. 15; P value < 0.05 was considered as statistically significant. RESULTS: After
      six months, a mean score of VASI decreased from 4.98 to 3.75 in patients applying
      topical Nigella sativa and from 4.98 to 4.62 in those using topical fish oil.
      Most of the percent improvement observed in upper extremities, trunk, head, and
      neck of those who received Nigella sativa and head, neck, trunk, and feet of
      those who received fish oil. No adverse effect was reported by the patients.
      CONCLUSIONS: Nigella sativa oil and fish oil were effective in reduction the size
      of patient's lesions; however, Nigella sativa was more effective in comparison to
      the fish oil. Therefore, using Nigella sativa with the major drugs in the
      treatment of vitiligo is recommended.

PMID- 25068061
TI  - Health concerns of Iranian adolescents: protocol for a mixed methods study.
AB  - BACKGROUND: Adolescents have particular health and developmental needs that
      suggest they should neither be treated as older children nor younger adults.
      OBJECTIVES: The aim of this paper is to report the protocol for a mixed methods
      study that set out to investigate the health concerns of Iranian adolescents and
      their sources of health information with the goal of identifying suitable
      strategies to address their health concerns. MATERIALS AND METHODS: This mixed
      methods study consists of an explanatory sequential design to be conducted in two
      phases. The first phase was a population-based cross-sectional survey of 915, 14
      18 year old adolescents who were selected by stratified cluster random sampling
      method from the 22 main municipal sectors of Tehran, Iran. They completed a
      series of self-administered questionnaires which were analyzed using quantitative
      approaches. The second phase was a qualitative study in which adolescents were
      selected using purposeful sampling for individual in-depth semi-structured
      interviews on the basis of the quantitative findings from the first phase. These
      data, together with a literature review and data obtained through nominal group
      technique, would then be used to in the development of strategies to reduce
      adolescents' health concerns. RESULTS: The findings of this mixed methods
      sequential explanatory study are expected to provide unique information about the
      health concerns of Iranian adolescents and their sources of information, which to
      date have received little attention. CONCLUSIONS: These data will provide a rich
      source of information that can be used by intervention programs, health
      professionals and policy makers in addressing the health concerns of adolescents,
      with the goal of facilitating a successful passage to adult life.

PMID- 25068062
TI  - Growth disorders among 6-year-old Iranian children.
AB  - BACKGROUND: Sociodemographic factors are important determinants of weight
      disorders. National representative studies provide a view on this health problem
      at national and regional levels. OBJECTIVES: This study aimed to assess the
      distribution of growth disorders in terms of body mass index (BMI) and height in
      6-year-old Iranian children using geographical information system (GIS).
      MATERIALS AND METHODS: In this cross-sectional nationwide survey, all Iranian
      children entering public and private elementary schools were examined in a
      mandatory national screening program in 2009. Descriptive analysis was used to
      calculate the prevalence of underweight, overweight, obesity, and short stature.
      Then, ArcGIS software was used to draw the figures. RESULTS: The study population
      consisted of 955388 children (48.5% girls and 76.5% urban). Overall, 20% of
      children were underweight, and 14.3% had high BMI, consisted of 10.9% overweight
      and 3.4% obese. The corresponding figure for short stature was 6.6%; however,
      these growth disorders were not equally distributed across various provinces.
      CONCLUSIONS: Our results confirmed unequal distribution of BMI and height of 6
      year-old children in Iran generally and in most of its provinces particularly.
      The differences among provinces cannot be fully explained by the socioeconomic
      pattern. These findings necessitate a comprehensive national policy with
      provincial evidence-based programs.

PMID- 25068063
TI  - Risk factors of neural tube defects in northern iran.
AB  - BACKGROUND: Neural tube defects (NTDs) including spina bifida and anencephaly are
      the second most common birth defects with 2.8 per 1000 births in northern Iran.
      OBJECTIVES: This study was conducted to determine the risk factors of neural tube
      defects in Gorgan, north of Iran. PATIENTS AND METHODS: This hospital-based, case
      control study was carried out on all NTD-affected pregnancies (n = 59) during
      February 2007 - August 2010, and 160 healthy pregnancies were selected via
      convenient sampling method in three hospitals in Gorgan, north of Iran. Risk
      factors including maternal body mass index (BMI), season of birth, gender of the
      newborn, mother's age, ethnicity, consanguineous marriage, folic acid
      consumption, nutrition, habitat, and education, were assessed through interviews
      with mothers. Univariate and multivariate logistic regression analyses were used
      to estimate the risks by odds ratios (ORs) and 95% confidence intervals. RESULTS:
      THE MULTIVARIATE ANALYSIS SHOWED THAT MATERNAL BMI (NORMAL/UNDERWEIGHT OR: 0.23,
      overweight/underweight OR: 0.15, obese/underweight OR: 0.13) and maternal
      ethnicity (Fars/Sistani OR: 3.49) and maternal nutrition (good/poor OR: 0.46)
      were significantly correlated with NTDs in the newborns. CONCLUSIONS: This study
      showed that maternal ethnicity, insufficient nutrition, and BMI, were the main
      risk factors of NTDs in northern Iran.

PMID- 25068064
TI  - An outcome measure of functionality and quality of life in patients with cervical
      myelopathy.
AB  - BACKGROUND: Cervical spondylotic myelopathy (CSM) is a common cause of
      significant clinical morbidity. The Japanese Orthopedic Association Cervical
      Myelopathy Evaluation Questionnaire (JOACMEQ) is a measure of health-related
      quality of life in these patients. OBJECTIVES: This study aimed to cross
      culturally translate and validate the JOACMEQ in Iran. PATIENTS AND METHODS: This
      study was a prospective clinical validation one. Forward-backward procedure was
      applied to translate the questionnaire from English into Persian. The translation
      and cross-cultural adaptation were performed in accordance with the published
      guidelines. A sample of patients with CSM was asked to respond to the
      questionnaire at two times: providing preoperative and postoperative assessments
      (6 months follow-up). To test the reliability, the internal consistency was
      assessed by Cronbach alpha coefficient and the validity was assessed by
      convergent validity. Responsiveness to change was also assessed comparing
      patients' preoperative and postoperative scores. RESULTS: All 87 patients
      completed the questionnaire. The Cronbach alpha coefficient for the JOACMEQ at
      preoperative and postoperative assessments ranged from 0.71 to 0.82 indicating a
      good internal consistency for the questionnaire. In addition, the correlation of
      each item with its hypothesized subscale of the JOACMEQ showed satisfactory
      results suggesting that the items had a substantial association with their own
      subscales. Further analysis also indicated that the questionnaire was responsive
      to change (P < 0.001). CONCLUSIONS: In general, the findings suggest that the
      Persian version of the JOACMEQ is a reliable and valid measure of functionality
      and quality of life evaluation among Iranian patients suffered from CSM.

PMID- 25068065
TI  - Bartholin's Gland Bilateral Nodular Hyperplasia: A Case Report Study.
AB  - INTRODUCTION: Tumors which originate from the Bartholin's glands (BGs) are very
      rare. Many solid masses that arise from the BGs are carcinoma, though these
      benign solid lesions are rare. CASE PRESENTATION: To the best of the reporter's
      knowledge, about 35 cases have been reported in the English literature so far,
      most of which accompanied with signs or symptoms of Bartholin's duct cyst. In
      this paper we report a 43-year-old woman with bilateral solid masses in the BGs,
      incidentally detected during anterior-posterior colpoperineoplasty. The masses
      were then excised. DISCUSSION: The histopathological examination showed increased
      number of acini with preserved duct-acinar connection, consistent with nodular
      hyperplasia. The patient had used oral contraceptive pill for four years.

PMID- 25068067
TI  - Risk factors of breast problems in mothers and its effects on newborns.
AB  - BACKGROUND: During lactation, especially the first few days after birth, some
      breast problems can cause pain and inadequate milk emptying. OBJECTIVES: This
      study aimed to investigate the risk factors of breast problems and their effect
      on neonatal complications. PATIENTS AND METHODS: This case-control study was
      conducted on 566 infants referred to Mashhad Ghaem Hospital clinic (from 2008 to
      2012) in Iran. Researchers filled out the questionnaire with the relevant
      neonatal and maternal information. They also recorded the mothers' breasts
      problems after examination. Then the infants were divided into two groups:
      Infants whose mothers complained from breast problems (case group), and the
      infants whose mothers did not have any breast problems (control group). Finally,
      two groups were compared with respect to the maternal and neonatal risk factors.
      RESULTS: THE TWO GROUPS WERE MATCHED ON THESE VARIABLES: parity (P = 0.861),
      maternal weight (P = 0.577), education level (P = 0.807), pregnancy complications
      (P = 0.383), gestational age (P = 0.161), Apgar score (P = 0.530), birth weight
      (P = 0.090), infant gender (P = 0.439), and infant age (P = 0.152). Case group
      vs. control group showed significant differences regarding prenatal care, mode of
      delivery, lactation status and the letdown reflex, serum sodium, frequency of
      urination and defecation, new weight and supplementation (P < 0.05). CONCLUSIONS:
      According to our study, breast problems were fewer in mothers who had prenatal
      care, normal vaginal delivery, proper breastfeeding position, and let down
      reflex. Neonatal complications of breast problems include pathologic weight loss
      and decrease in the frequency of urination. Therefore, special attention to
      mother's breasts during pregnancy and in the early days of delivery, and their
      appropriate treatment may reduce breast problems and related neonatal
      complications.

PMID- 25068066
TI  - Giving bad news: a qualitative research exploration.
AB  - BACKGROUND: The manner in which healthcare professionals deliver bad news affects
      the way it is received, interpreted, understood, and dealt with. Despite the fact
      that clinicians are responsible for breaking bad news, it has been shown that
      they lack skills necessary to perform this task. OBJECTIVES: The purpose of this
      study was to explore Iranian mothers' experiences to receive bad news about their
      children cancer and to summarize suggestions for improving delivering bad news by
      healthcare providers. MATERIALS AND METHODS: A qualitative approach using content
      analysis was adopted. Semi-structured interviews were conducted with 14 mothers
      from two pediatric hospitals in Iran. RESULTS: Five major categories emerged from
      the data analysis, including dumping information, shock and upset, emotional
      work, burden of delivering bad news to the family members, and a room for
      multidisciplinary approach. CONCLUSIONS: Effective communication of healthcare
      team with mothers is required during breaking bad news. Using multidisciplinary
      approaches to prevent harmful reactions and providing appropriate support are
      recommended.

PMID- 25068068
TI  - Quality assessment of peripartum care.
AB  - BACKGROUND: Maternal health improvement is one of the eight goals of the third
      millennium development, set in 2000. Pregnancy complications are the most
      important causes of maternal mortality worldwide. Proper and qualified health
      care access is one the most important factors for reducing maternal and neonatal
      mortality rates. OBJECTIVES: This study aimed to determine quality of peripartum
      care in Lorestan province in 2013. MATERIALS AND METHODS: This was a descriptive
      cross-sectional study, in which quality of peripartum care was assessed among 200
      women (sample size was determined according to other studies), referred to
      Lorestan province public hospitals. Quality assessment according to the WHO was
      used for the framework of structure, process and outcome. Data was collected by a
      researcher-made checklist, developed based on the administered instructions by
      Iran Health Ministry. The checklists were filled by observation. The calculated
      quality scores were expressed as percentage. SPSS version 18 was used for data
      analysis. RESULTS: The mean percentages of compatibility with desirable situation
      were 54%, 57% and 66% in first, second and third stage of labor, respectively.
      The lowest scores were related to: Leopold maneuvers in the first stage, hand
      washing in the second stage and pulse control in the third stage of labor.
      CONCLUSIONS: Quality of peripartum care is moderate in Lorestan province,
      therefore, continuous evaluation of quality of care by administrators and
      hospital staff is essential to improve this quality and will ultimately result in
      maternal and neonatal health improvement.

PMID- 25068069
TI  - Mixed form of hirsutism in an adolescent female and laser therapy.
AB  - INTRODUCTION: Hirsutism is a common disorder of excess growth of terminal hair in
      an androgen-dependent male distribution in women, including the chin, upper lip,
      breasts, back, and abdomen. It is very important to identify the etiology of
      hirsutism and adequate treat is prior to any cosmetic therapy. CASE PRESENTATION:
      The case was a 17-year-old female with severe hirsutism, oligomenorrhea, and
      obesity. She was evaluated to identify the etiology and diagnosed as a case of
      polycystic ovarian syndrome (PCOS), nonclassic congenital adrenal hyperplasia (NC
      CAH), and hyperandrogenic insulin-resistant acanthosis nigricans (HAIR-AN)
      syndrome, which is a rare combination of hirsutism etiology. She was successfully
      treated according to the underlying pathology, and laser photoepilation was used
      as the preferred hair removal method. DISCUSSION: Establishing the etiology,
      using the evidence-based strategies to improve hirsutism, and treating the
      underlying disorder, are essential for proper management of women with hirsutism.

PMID- 25068070
TI  - The Aryl Hydrocarbon Receptor: A Target for Breast Cancer Therapy.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that regulates a battery of genes in response to exposure to a broad class of
      environmental poly aromatic hydrocarbons (PAH). AhR is historically characterized
      for its role in mediating the toxicity and adaptive responses to these chemicals,
      however mounting evidence has established a role for it in ligand-independent
      physiological processes and pathological conditions, including cancer. The AhR is
      overexpressed and constitutively activated in advanced breast cancer cases and
      was shown to drive the progression of breast cancer. In this article we will
      review the current state of knowledge on the possible role of AhR in breast
      cancer and how it will be exploited in targeting AhR for breast cancer therapy.

PMID- 25068071
TI  - Residues Controlling Facial Selectivity in an Alkene Reductase and Semirational
      Alterations to Create Stereocomplementary Variants.
AB  - A systematic saturation mutagenesis campaign was carried out on an alkene
      reductase from Pichia stipitis (OYE 2.6) to develop variants with reversed
      stereoselectivities. Wild-type OYE 2.6 reduces three representative Baylis
      Hillman adducts to the corresponding S products with almost complete
      stereoselectivities and good catalytic efficiencies. We created and screened 13
      first-generation, site-saturation mutagenesis libraries, targeting residues found
      near the bound substrate. One variant (Tyr78Trp) showed high R selectivity toward
      one of the three substrates, but no change (cyclohexenone derivative) and no
      catalytic activity (acrylate derivative) for the other two. Subsequent rounds of
      mutagenesis retained the Tyr78Trp mutation and explored other residues that
      impacted stereoselectivity when altered in a wild-type background. These efforts
      yielded double and triple mutants that possessed inverted stereoselectivities for
      two of the three substrates (conversions >99% and at least 91% ee (R)). To
      understand the reasons underlying the stereochemical changes, we solved crystal
      structures of two key mutants: Tyr78Trp and Tyr78Trp/Ile113Cys, the latter with
      substrate partially occupying the active site. By combining these experimental
      data with modeling studies, we have proposed a rationale that explains the
      impacts of the most useful mutations.

PMID- 25068072
TI  - Palladium-Catalyzed Intra- and Intermolecular C-H Arylation Using Mesylates:
      Synthetic Scope and Mechanistic Studies.
AB  - This paper describes the development of Pd-catalyzed inter- and intramolecular
      direct arylation using mesylates. Furthermore, a sequential mesylation/arylation
      protocol using phenols as substrates is described. These transformations are
      general with respect to the electronics of the C-H substrates and allow for the
      synthesis of diverse heterocyclic motifs in good yields. Both arenes and
      heteroarenes efficiently participate in these reactions. Preliminary mechanistic
      studies are presented for both inter- and intramolecular arylations.

PMID- 25068073
TI  - Modified Lipoproteins in Diabetic Retinopathy: A Local Action in the Retina.
AB  - Clinical epidemiological studies have revealed relatively weak, yet statistically
      significant, associations between dyslipidemia/dyslipoproteinemia and diabetic
      retinopathy (DR). Recent large interventional studies, however, demonstrated an
      unexpectedly robust efficacy of fenofibrate on the development of DR, possibly
      independent of plasma lipids. To unify the apparent discrepancies, we hypothesize
      that plasma lipoproteins play an indirect but important role in DR, contingent on
      the integrity of the blood-retina-barrier (BRB). In retinas with an intact BRB,
      plasma lipoproteins may be largely irrelevant; however, important effects become
      operative after the BRB is impaired in diabetes, leading to lipoprotein
      extravasation and subsequent modification, hence toxicity to the neighbouring
      retinal cells. In this hypothesis, BRB leakage is the key, plasma lipoprotein
      concentrations mainly modulate its consequences, and fenofibrate has intra
      retinal actions. This review summarizes our current knowledge of the direct
      effects and mechanisms of modified lipoproteins on retinal cells and their
      potential contribution to the pathogenesis of DR.

PMID- 25068074
TI  - Assay for Glycosaminoglycans by Tandem Mass Spectrometry and its Applications.
AB  - Glycosaminoglycans (GAGs) are distributed in the whole body and play a variety of
      important physiological roles associated with inflammation, growth, coagulation,
      fibrinolysis, lipolysis, and cell-matrix biology. Accumulation of undegraded GAGs
      in lysosomes gives rise to a distinct clinical syndrome, mucopolysaccharidoses.
      Measurement of each specific GAG in a variety of specimens is urgently required
      to understand GAG interaction with other molecules, physiological status of
      patients, and prognosis and pathogenesis of the disease. We established a highly
      sensitive and accurate tandem mass spectrometry (LC-MS/MS) method for
      measurements of disaccharides derived from four specific GAGs [dermatan sulfate
      (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)].
      Disaccharides were produced by specific enzyme digestion of each GAG, and
      quantified by negative ion mode of multiple reaction monitoring. Subclasses of HS
      and GAGs with identical molecular weights can be separated using a
      Hypercarbcolumn (2.0 mm*50 mm, 5 MUm) with an aectonitrile gradient in ammonium
      acetate (pH 11.0). We also developed a GAG assay by RapidFire with tandem mass
      spectrometry (RF-MS/MS). The RF system consists of an integrated solid phase
      extraction robot that binds and de-salts samples from assay plates and directly
      injects them into a MS/MS detector, reducing sample processing time to ten
      seconds. RF-MS/MS consequently yields much faster throughput than conventional LC
      MS/MS-based methods. However, the RF system does not have a chromatographic step,
      and therefore, cannot distinguish GAGs that have identical molecular weights.
      Both methods can be applied to analysis of dried blood spots, blood, and urine
      specimens. In this article, we compare the assay methods for GAGs and describe
      their potential applications.

PMID- 25068075
TI  - MR Imaging of Stem Cell Transplants in Arthritic Joints.
AB  - About 43 million individuals in the US currently suffer from disabilities due to
      arthritis. Cartilage defects are the major source of pain in the affected joints.
      Current treatments, whilst alleviating some of the clinical symptoms, prove
      insufficient to cure the underlying irreversible cartilage loss. Stem cells
      represent a unique source for restoration of cartilage defects. Pre-clinical and
      clinical trials are currently pursued to investigate the potential of various
      types of stem cells and stem cell derived chondrocytes to repair arthritic
      joints. A major challenge with all stem cell-mediated tissue regeneration
      approaches is death of the transplanted cells with clearance by the immune
      system. Our current inability to diagnose successful or unsuccessful engraftment
      of transplanted cells non-invasively in vivo represents a major bottleneck for
      the development of successful stem cell therapies. A large variety of non
      invasive Magnetic Resonance (MR) imaging techniques have been developed over the
      last decade, which enable sensitive in vivo detection of Matrix Associated Stem
      Cell Implants (MASI) and early diagnosis of related complications. While
      initially focused on successfully harvesting cellular MR imaging approaches with
      easily applicable SuperParamagnetic Iron Oxide Nanoparticles (SPIO), our team
      began to observe details that will facilitate clinical translation. We therefore
      started a broader effort to define a comprehensive set of novel, clinically
      applicable imaging approaches for stem cell transplants in patients. We
      established immediately clinically applicable nanoparticle labeling techniques
      for tracking stem cell transplants with MR imaging; we have evaluated the long
      term MR signal effects of iron oxide nanoparticle labeled MASI in vivo; and we
      have defined distinct signal characteristics of labeled viable and apoptotic
      MASI. This review article will provide an overview over these efforts and discuss
      important implications for clinical translation.

PMID- 25068076
TI  - Measuring coding intensity in the Medicare Advantage program.
AB  - BACKGROUND: In 2004, Medicare implemented a system of paying Medicare Advantage
      (MA) plans that gave them greater incentive than fee-for-service (FFS) providers
      to report diagnoses. DATA: Risk scores for all Medicare beneficiaries 2004-2013
      and Medicare Current Beneficiary Survey (MCBS) data, 2006-2011. MEASURES: Change
      in average risk score for all enrollees and for stayers (beneficiaries who were
      in either FFS or MA for two consecutive years). Prevalence rates by Hierarchical
      Condition Category (HCC). RESULTS: Each year the average MA risk score increased
      faster than the average FFS score. Using the risk adjustment model in place in
      2004, the average MA score as a ratio of the average FFS score would have
      increased from 90% in 2004 to 109% in 2013. Using the model partially implemented
      in 2014, the ratio would have increased from 88% to 102%. The increase in
      relative MA scores appears to largely reflect changes in diagnostic coding, not
      real increases in the morbidity of MA enrollees. In survey-based data for 2006
      2011, the MA-FFS ratio of risk scores remained roughly constant at 96%. Intensity
      of coding varies widely by contract, with some contracts coding very similarly to
      FFS and others coding much more intensely than the MA average. Underpinning this
      relative growth in scores is particularly rapid relative growth in a subset of
      HCCs. DISCUSSION: Medicare has taken significant steps to mitigate the effects of
      coding intensity in MA, including implementing a 3.4% coding intensity adjustment
      in 2010 and revising the risk adjustment model in 2013 and 2014. Given the
      continuous relative increase in the average MA risk score, further policy changes
      will likely be necessary.

PMID- 25068077
TI  - Low Dietary Intake of Vitamin D and Vitamin D Deficiency in Hemodialysis
      Patients.
AB  - BACKGROUND: The purpose of this study was to test the hypothesis that decreased
      dietary intake of Vitamin D contributes to Vitamin D deficiency in end-stage
      renal disease (ESRD) patients on hemodialysis (HD). METHODS: We performed a cross
      sectional study of 58 hemodialysis outpatients from two Mount Sinai Medical
      Center (MSMC)-affiliated outpatient HD units in New York City and 648 outpatients
      at MSMC with CKD stages I-IV. Serum 25(OH)D concentrations were measured from
      August 2010 to July of 2011 in recruited hemodialysis patients (n=58) and linked
      with results of dietary and lifestyle surveys. The Mount Sinai Data Warehouse
      (electronic medical record) was used to capture 25(OH) Vitamin D levels for
      outpatients with CKD stages I-IV who had Vitamin D testing during the same time
      period. RESULTS: The prevalence of Vitamin D insufficiency/deficiency in the HD
      cohort was 96.6%. Mean (SD) and median (IQR) 25(OH)D concentrations were 15.65
      (6.82) and 13.55 (10.15) ng/mL, respectively. Dietary surveys showed a median
      weekly Vitamin D intake of 1044 IU (IQR=808, vs. a recommended weekly allowance
      of 4200 IU) and specific avoidance of foods containing both Vitamin D and
      phosphorus. In contrast, mean and median 25(OH)D concentrations in patients with
      CKD stages I-IV were 25.66 (13.44) and 23.60 (15.48) ng/mL (p<0.001 vs. HD
      patients). CONCLUSIONS: Vitamin D deficiency is more prevalent in HD patients
      than in pre-dialysis patients with CKD and is associated with decreased dietary
      intake of Vitamin D. Dialysis restrictions imposed to reduce dietary phosphorus
      intake likely contributes to the development of hypovitaminosis D in ESRD
      patients.

PMID- 25068078
TI  - Synergistic Effect of 1-Butyl-3-methylimidazolium Hexafluorophosphate and DMSO in
      the SARA ATRP at Room Temperature Affording Very Fast Reactions and Polymers with
      Very Low Dispersity.
AB  - An unusual synergistic effect between 1-butyl-3-methylimidazolium
      hexafluorophosphate (BMIM-PF6) and dimethyl sulfoxide (DMSO) mixtures is reported
      for the supplemental activator and reducing agent atom transfer radical
      polymerization (SARA ATRP) of methyl acrylate (MA) using a catalytic system
      composed by sodium dithionate (Na2S2O4) and CuBr2/Me6TREN (Me6TREN: tris[2
      (dimethylamino)ethyl]amine) at room temperature. To the best of our knowledge,
      the use of ionic liquids (IL) has never been reported for the SARA ATRP. The
      kinetic data obtained for a broad range of target molecular weights revealed very
      fast polymerization rates, low dispersity values (D < 1.05) and well-defined
      chain-end functionalities.

PMID- 25068079
TI  - Zinc-Catalyzed Highly Isoselective Ring Opening Polymerization of rac-Lactide.
AB  - A family of chiral zinc amido-oxazolinate complexes are shown to be highly active
      and isoselective initiators for the ring-opening polymerization (ROP) of rac
      lactide, yielding isotactic stereoblock polylactides (PLA) with Pm up to 0.91.
      This represents the highest isoselectivity observed with zinc-based catalysts for
      ROP of rac-lactide.

PMID- 25068080
TI  - Sociodemographic, Psychosocial, and Health Behavior Risk Factors Associated with
      Sexual Risk Behaviors among Southeastern US College Students.
AB  - OBJECTIVES: We examined correlates of 1) being a virgin; 2) drug or alcohol use
      prior to the last intercourse; and 3) condom use during the last intercourse in a
      sample of college students. METHODS: We recruited 24,055 students at six colleges
      in the Southeast to complete an online survey, yielding 4840 responses (20.1%
      response rate), with complete data from 4514. RESULTS: Logistic regression
      indicated that correlates of virginity included being younger (p < 0.001), male
      (p = 0.01), being White or other ethnicity (p < 0.001), attending a four-vs. two
      year school (p < 0.001), being single/never married (p < 0.001), lower sensation
      seeking (p < 0.001), more regular religious service attendance (p < 0.001), lower
      likelihood of smoking (p < 0.001) and marijuana use (p = 0.002), and less
      frequentdrinking (p < 0.001). Correlates of alcohol or drug use prior to most
      recent intercourse including being older (p = 0.03), being White (p < 0.01),
      attending a four-year college (p < 0.001), being homosexual (p = 0.041) or
      bisexual (p = 0.011), having more lifetime sexual partners (p = 0.005), lower
      satisfaction with life (p = 0.004), greater likelihood of smoking (p < 0.001) and
      marijuana use (p < 0.001), and more frequent drinking (p < 0.001). Correlates of
      condom use during the last sexual intercourse including being older (p = 0.003),
      being female (p < 0.001), being White (p < 0.001), attending a two-year school (p
      = 0.04), being single/never married (p = 0.005), being homosexual or bisexual (p
      = 0.04), and a more frequent drinking (p = 0.001). CONCLUSIONS: Four-year college
      attendees were more likely to be a virgin but, if sexually active, reported
      higher sexual risk behaviors. These nuances regarding sexual risk may provide
      targets for sexual health promotion programs and interventions.

PMID- 25068082
TI  - In this issue of Adipocyte.

PMID- 25068083
TI  - Bisphenol A increases aP2 expression in 3T3L1 by enhancing the transcriptional
      activity of nuclear receptors at the promoter.
AB  - Environmental pollutants, such as bisphenol A (BPA), have the potential to affect
      the differentiation processes and the biology of the adipose tissue. The 3T3-L1
      model is one of the murine cell models used extensively for the investigation of
      the molecular events that govern the differentiation of adipocytes from a
      committed preadipocyte to a mature, lipid laden adipocyte. Most of the studies
      investigating the effects of BPA on preadipocyte differentiation have
      investigated the effects of this chemical in the presence of an optimal
      differentiation cocktail containing high concentrations of the synthetic
      glucocorticoid dexamethasone, conditions that result in 90% to 100% of
      differentiated adipocytes. Our studies employed the 3T3-L1 cell model in the
      absence of exogenous glucocorticoids. We show that BPA is able to increase the
      differentiation of the 3T3-L1 cells under these conditions. Furthermore, the
      effect of BPA was observed in the absence of the synthetic glucocorticoid
      (dexamethasone), a hormone known to be required for the differentiation of the
      3T3-L1 cells. In addition, BPA upregulated the mRNA expression and protein levels
      of the terminal marker of adipogenesis the fatty acid binding protein (aP2) in
      these cells. Interestingly, the known modulators of adipogenesis such as the
      peroxisome proliferator-activated receptor (PPAR) gamma or CCAAT enhancer binding
      protein (C/EBP) alpha were not elevated at the mRNA or protein level in response
      to BPA. Furthermore, BPA upregulated the expression levels of the marker of
      adipogenesis aP2, through an effect on the transcriptional activity of C/EBPdelta
      and the glucocorticoid receptor (GR) at its promoter. 

PMID- 25068085
TI  - Gene expression in subcutaneous adipose tissue differs in women with polycystic
      ovary syndrome and controls matched pair-wise for age, body weight, and body mass
      index.
AB  - Adipose tissue dysfunction may be a central factor in the pathogenesis of insulin
      resistance in women with polycystic ovary syndrome (PCOS). Gene expression in
      subcutaneous adipose tissue in PCOS and its relation to metabolic and endocrine
      features of the syndrome have been fragmentarily investigated. The aim was to
      assess in subcutaneous adipose tissue the expression of genes potentially
      associated with adipose tissue dysfunction and to explore their relation to
      features of the syndrome. Twenty-one women with PCOS (body mass index [BMI] 18.2
      33.4 kg/m(2)) and 21 controls (BMI 19.2-31.7 kg/m(2)) were matched pair-wise for
      age, body weight, and BMI. Tissue biopsies were obtained to measure mRNA
      expression of 44 genes (TaqMan Low Density Array). Differential expression levels
      were correlated with BMI, glucose infusion rate (GIR), sex hormone binding
      globulin (SHBG), and sex steroids. In PCOS, expression of adiponectin receptor 2
      (ADIPOR2), LPL, and twist-related protein 1 (TWIST1) was decreased, while
      expression of chemokine (C-C motif) ligand 2 (CCL2) and heme oxygenase (decycling
      1) (HMOX1) was increased. TWIST1 and HMOX1, both novel adipokines, correlated
      with BMI and GIR. After BMI adjustment, LPL and ADIPOR2 expression correlated
      with plasma estradiol, and CCL2 expression correlated with GIR, in all women. We
      conclude that adipose tissue mRNA expression differed in PCOS women and controls
      and that two novel adipokines, TWIST1 and HMOX1, together with adiponectin, LPL,
      and CCL2, and their downstream pathways merit further investigation. 

PMID- 25068084
TI  - Visfatin is involved in TNFalpha-mediated insulin resistance via an
      NAD(+)/Sirt1/PTP1B pathway in 3T3-L1 adipocytes.
AB  - Tumor necrosis factor alpha (TNFalpha) is a well-known mediator of inflammation
      in the context of obesity in adipose tissue. Its action appears to be directly
      linked to perturbations of the insulin pathway, leading to the development of
      insulin resistance. Visfatin has been suspected to be linked to insulin
      sensitivity, but the mechanism involved is still partly unknown. The aim of this
      study was to evaluate the role of visfatin in the impairment of the insulin
      pathway by TNFalpha activity in 3T3-L1 adipocytes and to unveil the mechanisms
      involved in such impairment. We demonstrated in 3T3-L1 adipocytes that visfatin
      was involved in TNFalpha-mediated insulin resistance in adipocytes. Indeed, after
      TNFalpha treatment in 3T3-L1 cells, visfatin was downregulated, leading to
      decreased nicotinamide adenine dinucleotide (NAD(+)) concentrations in cells.
      This decrease was followed by a decrease in Sirt1 activity, which was linked to
      an increase in PTP1B expression. The modulation of PTP1B by visfatin was likely
      responsible for the observed decreases in glucose uptake and Akt phosphorylation
      in 3T3-L1 adipocytes. Here, we demonstrated a complete pathway involving
      visfatin, NAD(+), Sirt1, and PTP1B that led to the perturbation of insulin
      signaling by TNFalpha in 3T3-L1 adipocytes. 

PMID- 25068086
TI  - Low abdominal subcutaneous preadipocyte adipogenesis is associated with visceral
      obesity, visceral adipocyte hypertrophy, and a dysmetabolic state.
AB  - Subcutaneous adipose tissue expansion through adipogenesis is increasingly
      recognized as a major determinant of body fat distribution and obesity-related
      cardiometabolic alterations. Our objective was to assess whether adipogenic rates
      of cultured human primary preadipocytes from the visceral and subcutaneous
      compartments relate to visceral obesity and cardiometabolic alterations. We
      recruited 35 women undergoing gynecological surgery and assessed body fat
      distribution by CT as well as fasting plasma lipids and glycemia. Fat samples
      from the greater omentum and abdominal subcutaneous (SC) compartments were used
      to assess mature adipocyte cell size and establish primary preadipocyte cultures.
      Differentiation was induced using adipogenic media and adipogenic rates were
      assessed using Oil Red O (ORO) absorbance/DNA content ratio and glyceraldehyde 3
      phosphate dehydrogenase (G3PDH) activity/DNA of differentiated cells. We found a
      lower adipogenic capacity of omental (OM) preadipocytes than SC preadipocytes
      originating from the same women (P < 0.05). Whereas only OM cell size was
      different among groups of low vs high OM adipogenic rate, SC adipogenic rates
      were clearly related to increased OM cell size and dyslipidemia when women were
      separated on median value of either ORO/DNA or G3PDH activity/DNA ratios. When
      matched for BMI, women with low SC preadipocyte adipogenic rates had a higher
      visceral adipose tissue area (P < 0.01), omental adipocyte hypertrophy (P <
      0.05), higher VLDL-lipid content (P < 0.01) and higher fasting glycemia (P <
      0.05) than those with low SC adipogenic rates. In conclusion, low abdominal
      subcutaneous preadipocyte differentiation capacity in vitro is associated with
      visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state. 

PMID- 25068087
TI  - Characterization of Cre recombinase models for the study of adipose tissue.
AB  - The study of adipose tissue in vivo has been significantly advanced through the
      use of genetic mouse models. While the aP2-Cre(BI) and aP2-Cre(Salk) lines have
      been widely used to target adipose tissue, the specificity of these lines for
      adipocytes has recently been questioned. Here we characterize Cre recombinase
      activity in multiple cell populations of the major adipose tissue depots of these
      and other Cre lines using the membrane-Tomato/membrane-GFP (mT/mG) dual
      fluorescent reporter. We find that the aP2-Cre(BI) and aP2-Cre(Salk) lines lack
      specificity for adipocytes within adipose tissue, and that the aP2-Cre(BI) line
      does not efficiently target adipocytes in white adipose depots. Alternatively,
      the Adiponectin-CreERT line shows high efficiency and specificity for adipocytes,
      while the PdgfRalpha-CreERUCL and PdgfRalpha-CreERJHU lines do not efficiently
      target adipocyte precursor cells in the major adipose depots. Instead, we show
      that the PdgfRalpha-Cre line is preferable for studies targeting adipocyte
      precursor cells in vivo. 

PMID- 25068088
TI  - Contrast lipocryolysis: Pre- and post-session tempering improves clinical
      results.
AB  - Alternative crystal structures are possible for all lipids and each different
      crystal structure is called a polymorphic form. Inter-conversion between
      polymorphisms would imply the possibility of leaning crystal formation toward the
      most effective polymorphism for adipocyte destruction. Food industry has been
      tempering lipids for decades. Tempering technology applied to lipocryolysis gave
      birth to "contrast lipocryolysis", which involves pre- and post-lipocryolysis fat
      layer heating as part of a specific tempering protocol. In this study, we
      evaluated the skinfold thickness of 10 subjects after a single contrast
      lipocryolysis session and witnessed important and fast reductions. 

PMID- 25068089
TI  - Regulation of S100B in white adipose tissue by obesity in mice.
AB  - S100B is a calcium binding protein found in adipose tissue; however, relatively
      little is known about the physiologic regulation or distribution of the protein
      within this organ. We examined plasma S100B concentration and white adipose
      tissue (WAT) s100b mRNA levels in lean and diet-induced obese (DIO) mice. Plasma
      S100B levels were increased by obesity. In WAT, s100b gene expression was also
      significantly increased by obesity and this increase was reversed following
      weight-loss. s100b gene expression was detected in both the adipocyte-enriched
      and stromal-vascular fractions of WAT; however, the increase in s100b gene
      expression in obese animals was only detected in the adipocyte-enriched fraction.
      Our results support published in vitro data indicating that WAT S100B may
      contribute to obesity-associated inflammation. 

PMID- 25068090
TI  - Brown fat and vascular heat dissipation: The new cautionary tail.
AB  - Current efforts to treat obesity and associated disorders focus on the
      stimulation of energy expenditure by increasing thermogenesis, for instance
      through activating brown adipose tissue or more recently "beige" or "brite" fat,
      a relatively novel type of adipose tissue with putative thermogenic potential. In
      this commentary, we aim to provide an alternative perspective on the current
      trend of analyzing and manipulating thermogenesis, brought about by our recent
      publication, in which we investigated the unexpected hypermetabolic phenotype of
      an animal model with defective thyroid hormone receptor alpha1 signaling. These
      mice display elevated brown adipose tissue thermogenesis; surprisingly, however,
      their body temperature is lower, pointing to a defect in heat conservation. Using
      infrared thermography and wire myograph experiments, we revealed that the tail
      arteries of the mutant mice are less sensitive to contractile stimuli, which
      leads to insufficient peripheral vasoconstriction and heat loss over the tail
      surface. This heat loss in turn lowers body temperature and triggers the
      additional thermogenesis. Our findings add a new aspect to the role of thyroid
      hormone in thermoregulation, and encourage a more holistic view in future studies
      in the field of thermogenesis, including the often-overlooked heat dissipation
      and recordings of body temperature. 

PMID- 25068091
TI  - Glutathionylated products of lipid peroxidation: A novel mechanism of adipocyte
      to macrophage signaling.
AB  - Obesity-associated insulin resistance has long been linked to both increased
      adipocyte oxidative stress as well as the presence of inflammatory changes in
      adipose tissue, including the infiltration and activation of tissue-resident
      macrophages. In order to investigate the connections between obesity-associated
      oxidative stress in adipocytes and increased inflammation in adipose tissue
      associated with the development of insulin resistance, our laboratory recently
      demonstrated that adipocytes form glutathionylated products of oxidative stress
      including glutathionyl-4-hydroxy-2-nonenal (GS-HNE) and glutathionyl-1,4
      dihydroxynonene (GS-DHN). The abundance of both GS-HNE and GS-DHN were increased
      in the visceral adipose tissue of ob/ob mice and diet-induced obese, insulin
      resistant mice. Further, these products of lipid peroxidation were shown to
      induce inflammatory changes in macrophages. Finally, in a mouse model,
      overproduction of GS-HNE was associated with increased fasting glucose levels and
      moderately impaired glucose tolerance. Together, these findings suggest a novel
      mechanism by which obesity-induced oxidative stress in adipocytes may lead to
      activation of tissue-resident macrophages. As adipose tissue inflammation has
      been shown to play an important role in the development of insulin resistance,
      further study of this pathway may lead to potential interventions to attenuate
      the metabolic consequences of obesity. 

PMID- 25068092
TI  - Comparison of a MEMS-Based Handheld OCT Scanner With a Commercial Desktop OCT
      System for Retinal Evaluation.
AB  - PURPOSE: The goal of this study was to evaluate the ability of our handheld
      optical coherence tomography (OCT) scanner to image the posterior and anterior
      structures of the human eye, and especially the individual layers of the retina,
      and to compare its diagnostic performance with that of a fixed desktop commercial
      ophthalmic OCT system. METHODS: We compared the clinical imaging results of our
      handheld OCT with a leading commercial desktop ophthalmic system (RTVue) used in
      specialist offices. Six patients exhibiting diabetes-related retinal pathology
      had both eyes imaged with each OCT system. RESULTS: In both sets of images, the
      structural irregularities of the retinal layers could be identified such as
      retinal edema and vitreomacular traction. CONCLUSIONS: Our handheld OCT system
      can be used to identify relevant anatomical structures and pathologies in the
      eye, potentially enabling earlier screening, disease detection, and treatment.
      Images can be acquired quickly, with sufficient resolution and negligible motion
      artifacts that would normally limit its diagnostic use. TRANSLATIONAL RELEVANCE:
      Following screening and early disease detection in primary care via our optimized
      handheld OCT system, patients can be referred to a specialist for treatment,
      preventing further disease progression. While many primary care physicians are
      adept at using the ophthalmoscope, they can definitely take advantage of more
      advanced technologies.

PMID- 25068094
TI  - A New Stochastic Kriging Method for Modeling Multi-Source Exposure-Response Data
      in Toxicology Studies.
AB  - One of the most fundamental steps in risk assessment is to quantify the exposure
      response relationship for the material/chemical of interest. This work develops a
      new statistical method, referred to as SKQ (stochastic kriging with qualitative
      factors), to synergistically model exposure-response data, which often arise from
      multiple sources (e.g., laboratories, animal providers, and shapes of
      nanomaterials) in toxicology studies. Compared to the existing methods, SKQ has
      several distinct features. First, SKQ integrates data across multiple sources and
      allows for the derivation of more accurate information from limited data. Second,
      SKQ is highly flexible and able to model practically any continuous response
      surfaces (e.g., dose-time-response surface). Third, SKQ is able to accommodate
      variance heterogeneity across experimental conditions and to provide valid
      statistical inference (i.e., quantify uncertainties of the model estimates).
      Through empirical studies, we have demonstrated SKQ's ability to efficiently
      model exposure-response surfaces by pooling information across multiple data
      sources. SKQ fits into the mosaic of efficient decision-making methods for
      assessing the risk of a tremendously large variety of nanomaterials and helps to
      alleviate safety concerns regarding the enormous amount of new nanomaterials.

PMID- 25068095
TI  - Impedance Biosensors: Applications to Sustainability and Remaining Technical
      Challenges.
AB  - Due to their all-electrical nature, impedance biosensors have significant
      potential for use as simple and portable sensors for environmental studies and
      environmental monitoring. Detection of two endocrine-disrupting chemicals (EDC),
      norfluoxetine and BDE-47, is reported here by impedance biosensing, with a
      detection limit of 8.5 and 1.3 ng/mL for norfluoxetine and BDE-47, respectively.
      Although impedance biosensors have been widely studied in the academic
      literature, commercial applications have been hindered by several technical
      limitations, including possible limitations to small analytes, the complexity of
      impedance detection, susceptibility to nonspecific adsorption, and stability of
      biomolecule immobilization. Recent research into methods to overcome these
      obstacles is briefly reviewed. New results demonstrating antibody regeneration
      atop degenerate (highly doped) Si are also reported. Using 0.2 M KSCN and 10 mM
      HF for antibody regeneration, peanut protein Ara h 1 is detected daily during a
      30 day trial.

PMID- 25068093
TI  - Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane.
AB  - Age-related macular degeneration (AMD) is the leading cause of legal blindness in
      older people in the developed world. The disease involves damage to the part of
      the retina responsible for central vision. Degeneration of retinal pigment
      epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to
      visual loss. Over the past decades, scientists and clinicians have tried to
      replace lost RPE cells in patients with AMD using cells from different sources.
      In recent years, advances in generating RPE cells from stem cells have been made
      and clinical trials are currently evaluating the safety and efficiency of
      replacing the degenerated RPE cell layer with stem cell-derived RPE cells.
      However, the therapeutic success of transplantation of stem cell-derived RPE
      cells may be limited unless the transplanted cells can adhere and survive in the
      long term in the diseased eye. One hallmark of AMD is the altered extracellular
      environment of Bruch's membrane to which the grafted cells have to adhere. Here,
      we discuss recent approaches to overcome the inhibitory environment of the
      diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim
      is to highlight novel approaches that may have the potential to improve the
      efficacy of RPE transplantation for AMD in the future.

PMID- 25068096
TI  - Cytotoxicity of ZnO Nanoparticles Can Be Tailored by Modifying Their Surface
      Structure: A Green Chemistry Approach for Safer Nanomaterials.
AB  - ZnO nanoparticles (NP) are extensively used in numerous nanotechnology
      applications; however, they also happen to be one of the most toxic
      nanomaterials. This raises significant environmental and health concerns and
      calls for the need to develop new synthetic approaches to produce safer ZnO NP,
      while preserving their attractive optical, electronic, and structural properties.
      In this work, we demonstrate that the cytotoxicity of ZnO NP can be tailored by
      modifying their surface-bound chemical groups, while maintaining the core ZnO
      structure and related properties. Two equally sized (9.26 +/- 0.11 nm) ZnO NP
      samples were synthesized from the same zinc acetate precursor using a forced
      hydrolysis process, and their surface chemical structures were modified by using
      different reaction solvents. X-ray diffraction and optical studies showed that
      the lattice parameters, optical properties, and band gap (3.44 eV) of the two ZnO
      NP samples were similar. However, FTIR spectroscopy showed significant
      differences in the surface structures and surface-bound chemical groups. This led
      to major differences in the zeta potential, hydrodynamic size, photocatalytic
      rate constant, and more importantly, their cytotoxic effects on Hut-78 cancer
      cells. The ZnO NP sample with the higher zeta potential and catalytic activity
      displayed a 1.5-fold stronger cytotoxic effect on cancer cells. These results
      suggest that by modifying the synthesis parameters/conditions and the surface
      chemical structures of the nanocrystals, their surface charge density, catalytic
      activity, and cytotoxicity can be tailored. This provides a green chemistry
      approach to produce safer ZnO NP.

PMID- 25068097
TI  - Real-Time Nanoparticle-Cell Interactions in Physiological Media by Atomic Force
      Microscopy.
AB  - Particle-cell interactions in physiological media are important in determining
      the fate and transport of nanoparticles and biological responses to them. In this
      work, these interactions are assessed in real time using a novel atomic force
      microscopy (AFM) based platform. Industry-relevant CeO2 and Fe2O3 engineered
      nanoparticles (ENPs) of two primary particle sizes were synthesized by the flame
      spray pyrolysis (FSP) based Harvard Versatile Engineering Nanomaterials
      Generation System (Harvard VENGES) and used in this study. The ENPs were attached
      on AFM tips, and the atomic force between the tip and lung epithelia cells
      (A549), adhered on a substrate, was measured in biological media, with and
      without the presence of serum proteins. Two metrics were used to assess the
      nanoparticle cell: the detachment force required to separate the ENP from the
      cell and the number of bonds formed between the cell and the ENPs. The results
      indicate that these atomic level ENP-cell interaction forces strongly depend on
      the physiological media. The presence of serum proteins reduced both the
      detachment force and the number of bonds by approximately 50% indicating the
      important role of the protein corona on the particle cell interactions.
      Additionally, it was shown that particle to cell interactions were size and
      material dependent.

PMID- 25068099
TI  - Differential Parental Influence in the Familial Aggregation of Obsessive
      Compulsive Disorder.
AB  - The familial nature of OCD has been well established. Clinical characteristics
      such as early age of onset, comorbidity with tic disorders, and higher rates of
      symmetry symptoms have been associated with the familial aggregation of OCD,
      though little research has examined the differential impact of paternal and
      maternal OCD. The current study explored parental influence on the expression of
      these characteristics and reports on 310 probands diagnosed with OCD as well as
      1,580 of their biological first-degree relatives. The probands were evaluated by
      trained clinical raters using semi-structured assessments, and relative diagnoses
      were obtained based on probands' reports. Similar to previous findings, 10.13% of
      the 1,580 relatives (n = 160) were reported to have significant OCD symptoms.
      Only probands who reported having a father with OCD, rather than any first-degree
      relative, were more likely to have an early age of onset, symmetry and exactness
      obsessions, and higher rates of comorbidity. No significant differences were
      found with respect to the probands who reported their mothers as having OCD.
      These findings suggest that paternal OCD, rather than simply any first-degree
      relative having OCD, may influence whether probands exhibit the clinical
      characteristics commonly associated with the familial subtype of OCD.

PMID- 25068098
TI  - Barriers to drug delivery in solid tumors.
AB  - Over the last decade, significant progress has been made in the field of drug
      delivery. The advent of engineered nanoparticles has allowed us to circumvent the
      initial limitations to drug delivery such as pharmacokinetics and solubility.
      However, in spite of significant advances to tumor targeting, an effective
      treatment strategy for malignant tumors still remains elusive. Tumors possess
      distinct physiological features which allow them to resist traditional treatment
      approaches. This combined with the complexity of the biological system presents
      significant hurdles to the site-specific delivery of therapeutic drugs. One of
      the key features of engineered nanoparticles is that these can be tailored to
      execute specific functions. With this review, we hope to provide the reader with
      a clear understanding and knowledge of biological barriers and the methods to
      exploit these characteristics to design multifunctional nanocarriers, effect
      useful dosing regimens and subsequently improve therapeutic outcomes in the
      clinic. 

PMID- 25068100
TI  - Cytochrome P450 2C24: Expression, Tissue Distribution, High-Throughput Assay, and
      Pharmacological Inhibition.
AB  - Cytochrome P450 (CYP)-mediated epoxidation of arachidonic acid (AA) contributes
      to important biological functions, including the pain-relieving responses
      produced by analgesic drugs. However, the relevant epoxygenase(s) remain
      unidentified. Presently, we describe the tissue distribution, high-throughput
      assay, and pharmacological characteristics of the rat epoxygenase CYP2C24.
      Following cloning from male rat liver, recombinant baculovirus containing the C
      terminal His-tagged cDNA was constructed and used to express the protein in
      Spodoptera frugiperda (Sf9) cells. Enzymatic activity was detected with
      membranes, NADPH regenerating system and CYP reductase, and optimized for high
      throughput screening by use of the Vivid Blue(c) BOMCC fluorescence substrate.
      Quantitative real-time PCR identified CYP2C24 m-RNA in liver, kidney, heart,
      lung, gonad and brain. Screening of CYP2C24 activity against a panel of
      inhibitors showed a very strong correlation with activity against the human
      homologue CYP2C19. In agreement with recent findings on CYP2C19, the epoxygenase
      blockers PPOH and MS-PPOH inhibited CYP2C24 only weakly, confirming that these
      drugs are not universal epoxygenase inhibitors. Finally, comparisons of the
      CYP2C24 inhibitor profile with anti-analgesic activity suggests that this isoform
      does not contribute to brain analgesic drug action. The present methods and
      pharmacological data will aid in study of the biological significance of this CYP
      isoform.

PMID- 25068101
TI  - The Associations of Indices of Obesity with Lipoprotein Subfractions in Japanese
      American, African American and Korean Men.
AB  - BACKGROUND: Both indices of obesity and lipoprotein subfractions contribute to
      coronary heart disease risk. However, associations between indices of obesity and
      lipoprotein subfractions remain undetermined across different ethnic groups. This
      study aims to examine the associations of indices of obesity in Japanese
      Americans (JA), African Americans (AA) and Koreans with lipoprotein subfractions.
      METHODS: A population-based sample of 230 JA, 91 AA, and 291 Korean men aged 40
      49 was examined for indices of obesity, i.e., visceral and subcutaneous adipose
      tissue (VAT and SAT, respectively), waist circumference (WC), and body-mass index
      (BMI), and for lipoprotein subfractions by nuclear-magnetic-resonance
      spectroscopy. Multiple regression analyses were performed in each of the three
      ethnic groups to examine the associations of each index of obesity with
      lipoprotein. RESULTS: VAT had significant positive associations with total and
      small low-density lipoprotein (LDL) and a significant negative association with
      large high-density lipoprotein (HDL) in all three ethnicities (p < 0.01). SAT,
      WC, and BMI had significant positive associations with total and small LDL in
      only JA and Koreans, while these indices had significant inverse associations
      with large HDL in all ethnic groups (p < 0.01). Compared to SAT, VAT had larger
      R2 values in the associations with total and small LDL and large HDL in all three
      ethnic groups. CONCLUSIONS: VAT is significantly associated with total and small
      LDL and large HDL in all three ethnic groups. The associations of SAT, WC, and
      BMI with lipoprotein subfractions are weaker compared to VAT in all three ethnic
      groups.

PMID- 25068102
TI  - Early relapse of Burkitt lymphoma heralded by a bone marrow necrosis and numb
      chin syndrome successfully treated with allogeneic stem cell transplantation.
AB  - The optimal salvage therapy for patients with relapsed Burkitt lymphoma is
      unknown. Bone marrow necrosis is an underreported (<1% of bone marrow failures).
      Numb chin syndrome is another rare syndrome associated with aggressive
      malignancies. Survival of these syndromes is dictated by the underlying disease
      and is usually dismal. Our 35-year-old patient experienced an early relapse of
      Burkitt lymphoma accompanied by syndromes, achieved second complete remission and
      underwent allogeneic stem cell transplantation. He remains alive and well >2
      years after the transplant. To our knowledge, this is the longest reported
      survival of the two syndromes in the setting of BL relapse. 

PMID- 25068103
TI  - Identification of a novel SEPT9-ABL1 fusion gene in a patient with T-cell
      prolymphocytic leukemia.
AB  - T-cell prolymphocytic leukemia (T-PLL), a rare type of peripheral T-cell
      leukemia, is characterized by marked splenomegaly with rapidly progressive
      lymphocytosis and a poor prognosis. Nine kinds of ABL1 chimeric genes have been
      identified in various kinds of hematological malignancies, such as chronic
      myeloid leukemia and B- or T-lymphoblastic leukemia. However, there have been no
      reports describing T-PLL cases with ABL1 rearrangements. We herein report a case
      of T-PLL with a novel SEPT9-ABL1 fusion gene which induced strong resistance to
      tyrosine kinase inhibitors such as imatinib and dasatinib. 

PMID- 25068104
TI  - An exploratory phase 2 study of investigational Aurora A kinase inhibitor
      alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes.
AB  - Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK)
      inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML)
      or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in
      21-day cycles. Responses in 6/35 AML patients (17% response rate with an
      additional 49% stable disease, 34% transfusion independence) included 1 complete
      response lasting >1 year. No responses were observed in MDS patients. Adverse
      events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and
      stomatitis. Results suggest modest activity in AML, supporting further research
      to better understand how AAK inhibition may induce leukemic cell senescence. 

PMID- 25068105
TI  - Prospective longitudinal MRI study of brain volumes and diffusion changes during
      the first year after moderate to severe traumatic brain injury.
AB  - The objectives of this prospective study in 62 moderate-severe TBI patients were
      to investigate volume change in cortical gray matter (GM), hippocampus,
      lenticular nucleus, lobar white matter (WM), brainstem and ventricles using a
      within subject design and repeated MRI in the early phase (1-26 days) and 3 and
      12 months postinjury and to assess changes in GM apparent diffusion coefficient
      (ADC) in normal appearing tissue in the cortex, hippocampus and brainstem. The
      impact of Glasgow Coma Scale (GCS) score at admission, duration of post-traumatic
      amnesia (PTA), and diffusion axonal injury (DAI) grade on brain volumes and ADC
      values over time was assessed. Lastly, we determined if MRI-derived brain volumes
      from the 3-month scans provided additional, significant predictive value to 12
      month outcome classified with the Glasgow Outcome Scale-Extended after adjusting
      for GCS, PTA and age. Cortical GM loss was rapid, largely finished by 3 months,
      but the volume reduction was unrelated to GCS score, PTA, or presence of DAI.
      However, cortical GM volume at 3 months was a significant independent predictor
      of 12-month outcome. Volume loss in the hippocampus and lenticular nucleus was
      protracted and statistically significant first at 12 months. Slopes of volume
      reduction over time for the cortical and subcortical GGM were significantly
      different. Hippocampal volume loss was most pronounced and rapid in individuals
      with PTA > 2 weeks. The 3-month volumes of the hippocampus and lentiform nucleus
      were the best independent predictors of 12-month outcome after adjusting for GCS,
      PTA and age. In the brainstem, volume loss was significant at both 3 and 12
      months. Brainstem volume reduction was associated with lower GCS score and the
      presence of DAI. Lobar WM volume was significantly decreased first after 12
      months. Surprisingly DAI grade had no impact on lobar WM volume. Ventricular
      dilation developed predominantly during the first 3 months, and was strongly
      associated with volume changes in the brainstem and cortical GM, but not lobar WM
      volume. Higher ADC values were detected in the cortex in individuals with severe
      TBI, DAI and PTA > 2 weeks, from 3 months. There were no associations between ADC
      values and brain volumes, and ADC values did not predict outcome. 

PMID- 25068106
TI  - fMRI evidence of improved visual function in patients with progressive retinitis
      pigmentosa by eye-movement training.
AB  - To evaluate changes in the visual processing of patients with progressive
      retinitis pigmentosa (RP) who acquired improved reading capability by eye
      movement training (EMT), we performed functional magnetic resonance imaging
      (fMRI) before and after EMT. Six patients with bilateral concentric contraction
      caused by pigmentary degeneration of the retina and 6 normal volunteers were
      recruited. Patients were given EMT for 5 min every day for 8-10 months. fMRI data
      were acquired on a 3.0-Tesla scanner while subjects were performing reading
      tasks. In separate experiments (before fMRI scanning), visual performances for
      readings were measured by the number of letters read correctly in 5 min. Before
      EMT, activation areas of the primary visual cortex of patients were 48.8% of
      those of the controls. The number of letters read correctly in 5 min was 36.6% of
      those by the normal volunteers. After EMT, the activation areas of patients were
      not changed or slightly decreased; however, reading performance increased in 5 of
      6 patients, which was 46.6% of that of the normal volunteers (p< 0.05). After
      EMT, increased activity was observed in the frontal eye fields (FEFs) of all
      patients; however, increases in the activity of the parietal eye fields (PEFs)
      were observed only in patients who showed greater improvement in reading
      capability. The improvement in reading ability of the patients after EMT is
      regarded as an effect of the increased activity of FEF and PEF, which play
      important roles in attention and working memory as well as the regulation of eye
      movements. 

PMID- 25068107
TI  - Neonatal physiological correlates of near-term brain development on MRI and DTI
      in very-low-birth-weight preterm infants.
AB  - Structural brain abnormalities identified at near-term age have been recognized
      as potential predictors of neurodevelopment in children born preterm. The aim of
      this study was to examine the relationship between neonatal physiological risk
      factors and early brain structure in very-low-birth-weight (VLBW) preterm infants
      using structural MRI and diffusion tensor imaging (DTI) at near-term age.
      Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk
      factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW
      <= 1500 g, gestational age (GA) <= 32 weeks), who were admitted to the Lucile
      Packard Children's Hospital, Stanford NICU and recruited to participate prior to
      routine near-term brain MRI conducted at 36.6 +/- 1.8 weeks postmenstrual age
      (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain
      abnormalities were assessed qualitatively on structural MRI, and white matter
      (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions
      defined by DiffeoMap neonatal brain atlas. Specific regions of interest included
      the genu and splenium of the corpus callosum, anterior and posterior limbs of the
      internal capsule, the thalamus, and the globus pallidus. Regional fractional
      anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and
      examined in relation to neonatal physiological risk factors including gestational
      age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC),
      retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C
      reactive protein (CRP), glucose, albumin, and total bilirubin. Brain
      abnormalities were observed on structural MRI in 38/102 infants including 35% of
      females and 40% of males. Infants with brain abnormalities observed on MRI had
      higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and
      peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs.
      0.67 mg/dL, p= .006) compared to those without. The number of signal
      abnormalities observed on structural MRI correlated to mean and peak CRP (rho =
      .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed
      on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p=
      .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the
      strongest associations with neonatal risk factors. Higher thalamus MD on the left
      and right, respectively, was associated with lower GA (r = -.322, p = .009; r= 
      .381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and
      lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that
      at near-term age, thalamus WM microstructure may be particularly vulnerable to
      certain neonatal risk factors. Interactions between albumin, bilirubin,
      phototherapy, and brain development warrant further investigation. Identification
      of physiological risk factors associated with selective vulnerability of certain
      brain regions at near-term age may clarify the etiology of neurodevelopmental
      impairment and inform neuroprotective treatment for VLBW preterm infants. 

PMID- 25068108
TI  - Linking DMN connectivity to episodic memory capacity: what can we learn from
      patients with medial temporal lobe damage?
AB  - Computational models predict that focal damage to the Default Mode Network (DMN)
      causes widespread decreases and increases of functional DMN connectivity. How
      such alterations impact functioning in a specific cognitive domain such as
      episodic memory remains relatively unexplored. Here, we show in patients with
      unilateral medial temporal lobe epilepsy (mTLE) that focal structural damage
      leads indeed to specific patterns of DMN functional connectivity alterations,
      specifically decreased connectivity between both medial temporal lobes (MTLs) and
      the posterior part of the DMN and increased intrahemispheric anterior-posterior
      connectivity. Importantly, these patterns were associated with better and worse
      episodic memory capacity, respectively. These distinct patterns, shown here for
      the first time, suggest that a close dialogue between both MTLs and the posterior
      components of the DMN is required to fully express the extensive repertoire of
      episodic memory abilities. 

PMID- 25068109
TI  - Integration of multimodal MRI data via PCA to explain language performance.
AB  - OBJECTIVE/METHODS: Neuroimaging research has predominantly focused on exploring
      how cortical or subcortical brain abnormalities are related to language
      dysfunction in patients with neurological disease through the use of single
      modality imaging. Still, limited knowledge exists on how various MRI measures
      relate to each other and to patients' language performance. In this study, we
      explored the relationship between measures of regional cortical thickness, gray
      white matter contrast (GWMC), white matter diffusivity [mean diffusivity (MD) and
      fractional anisotropy (FA)] and the relative contributions of these MRI measures
      to predicting language function across patients with temporal lobe epilepsy (TLE)
      and healthy controls. T1- and diffusion-weighted MRI data were collected from 56
      healthy controls and 52 patients with TLE. By focusing on frontotemporal regions
      implicated in language function, we reduced each domain of MRI data to its
      principal component (PC) and quantified the correlations among these PCs and the
      ability of these PCs to explain the variation in vocabulary, naming and fluency.
      We followed up our significant findings by assessing the predictive power of the
      implicated PCs with respect to language impairment in our sample. RESULTS: We
      found significant positive associations between PCs representing cortical
      thickness, GWMC and FA that appeared to be partially mediated by changes in total
      brain volume. We also found a significant association between reduced FA and
      increased MD after controlling for confounding factors (e.g., age, field
      strength, total brain volume). Reduced FA was significantly associated with
      reductions in visual naming while increased MD was associated with reductions in
      auditory naming scores, even after controlling for the variability explained by
      reductions in hippocampal volumes. Inclusion of FA and MD PCs in predictive
      models of language impairment resulted in significant improvements in sensitivity
      and specificity of the predictions. CONCLUSIONS: Quantitative MRI measures from
      T1 and diffusion-weighted scans are unlikely to represent perfectly orthogonal
      vectors of disease in individuals with epilepsy. On the contrary, they exhibit
      highly intercorrelated PCs in their factor structures, which is consistent with
      an underlying pathological process that affects both the cortical and the
      subcortical structures simultaneously. In addition to hippocampal volume, the PCs
      of diffusion weighted measures (FA and MD) increase the sensitivity and
      specificity for determining naming impairment in patients with TLE. These
      findings underline the importance of combining multimodal imaging measures to
      better predict language performance in TLE that could extend to other patients
      with prominent language impairments.

PMID- 25068110
TI  - Evidence for brainstem network disruption in temporal lobe epilepsy and sudden
      unexplained death in epilepsy.
AB  - The symptoms witnessed in unexplained death in epilepsy (SUDEP) suggest a
      breakdown of central autonomic control. Since the brainstem plays a crucial role
      in autonomic control, the objectives of this study were 1. To investigate if
      temporal lobe epilepsy (TLE) is associated with brainstem atrophy and to
      characterize it using graph Analysis 2. To compare the findings with those in two
      probable TLESUDEP. T1 images were obtained from 17 controls, 30 TLE (16 with
      mesial-temporal-sclerosis (TLE-MTS) and 14 without (TLE-no)) and from 2 patients
      who died of SUDEP. The brainstem was extracted, warped onto a brainstem atlas and
      Jacobian determinants maps (JDM) calculated. SPM8 was used to compare the JDMs at
      the group level, z-score maps were calculated for single subject analysis.
      Brainstem regions encompassing autonomic structures were identified based on
      macroscopic landmarks and mean z-scores from 5 * 5 * 5 voxel cubes extracted to
      calculate a new measure called atrophy-similarity index (ASI) for graph analysis.
      TLE-MTS had volume loss in the dorsal mesencephalon. The SUDEP cases had severe
      and more extensive volume loss in the same region. Nodal degrees and
      participation coefficients were decreased and local efficiency increased in SUDEP
      compared to controls. TLE is associated with volume loss in brainstem regions
      involved in autonomic control. Structural damage in these regions might increase
      the risk for a fatal dysregulation during situations with increased demand such
      as following severe seizures. 

PMID- 25068112
TI  - Striatal connectivity changes following gambling wins and near-misses:
      Associations with gambling severity.
AB  - Frontostriatal circuitry is implicated in the cognitive distortions associated
      with gambling behaviour. 'Near-miss' events, where unsuccessful outcomes are
      proximal to a jackpot win, recruit overlapping neural circuitry with actual
      monetary wins. Personal control over a gamble (e.g., via choice) is also known to
      increase confidence in one's chances of winning (the 'illusion of control').
      Using psychophysiological interaction (PPI) analyses, we examined changes in
      functional connectivity as regular gamblers and non-gambling participants played
      a slot-machine game that delivered wins, near-misses and full-misses, and
      manipulated personal control. We focussed on connectivity with striatal seed
      regions, and associations with gambling severity, using voxel-wise regression.
      For the interaction term of near-misses (versus full-misses) by personal choice
      (participant-chosen versus computer-chosen), ventral striatal connectivity with
      the insula, bilaterally, was positively correlated with gambling severity. In
      addition, some effects for the contrast of wins compared to all non-wins were
      observed at an uncorrected (p < .001) threshold: there was an overall increase in
      connectivity between the striatal seeds and left orbitofrontal cortex and
      posterior insula, and a negative correlation for gambling severity with the
      connectivity between the right ventral striatal seed and left anterior cingulate
      cortex. These findings corroborate the 'non-categorical' nature of reward
      processing in gambling: near-misses and full-misses are objectively identical
      outcomes that are processed differentially. Ventral striatal connectivity with
      the insula correlated positively with gambling severity in the illusion of
      control contrast, which could be a risk factor for the cognitive distortions and
      loss-chasing that are characteristic of problem gambling. 

PMID- 25068111
TI  - Neuroimaging essentials in essential tremor: a systematic review.
AB  - BACKGROUND: Essential tremor is regarded to be a disease of the central nervous
      system. Neuroimaging is a rapidly growing field with potential benefits to both
      diagnostics and research. The exact role of imaging techniques with respect to
      essential tremor in research and clinical practice is not clear. A systematic
      review of the different imaging techniques in essential tremor is lacking in the
      literature. METHODS: We performed a systematic literature search combining the
      terms essential tremor and familial tremor with the following keywords: imaging,
      mri, vbm, dwi, fmri, pet and spect, both in abbreviated form as well as in full
      form. We summarize and discuss the quality and the external validity of each
      study and place the results in the context of existing knowledge regarding the
      pathophysiology of essential tremor. RESULTS: A total of 48 neuroimaging studies
      met our search criteria, roughly divided into 19 structural and 29 functional and
      metabolic studies. The quality of the studies varied, especially concerning
      inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity
      during rest and during tremor. The studies also pointed to the involvement of the
      thalamus, the inferior olive and the red nucleus. Structural studies showed less
      consistent results. DISCUSSION AND CONCLUSION: Neuroimaging techniques in
      essential tremor give insight into the pathophysiology of essential tremor
      indicating the involvement of the cerebellum as the most consistent finding.
      GABAergic dysfunction might be a major premise in the pathophysiological
      hypotheses. Inconsistencies between studies can be partly explained by the
      inclusion of heterogeneous patient groups. Improvement of scientific research
      requires more stringent inclusion criteria and application of advanced analysis
      techniques. Also, the use of multimodal neuroimaging techniques is a promising
      development in movement disorders research. Currently, the role of imaging
      techniques in essential tremor in daily clinical practice is limited.

PMID- 25068113
TI  - Parkinson's disease-related perfusion and glucose metabolic brain patterns
      identified with PCASL-MRI and FDG-PET imaging.
AB  - INTRODUCTION: Under normal conditions, the spatial distribution of resting
      cerebral blood flow and cerebral metabolic rate of glucose are closely related. A
      relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin
      labeling (PCASL), can be used to measure regional brain perfusion. We identified
      a Parkinson's disease (PD)-related perfusion and metabolic covariance pattern in
      the same patients using PCASL and FDG-PET imaging and assessed (dis)similarities
      in the disease-related pattern between perfusion and metabolism in PD patients.
      METHODS: Nineteen PD patients and seventeen healthy controls underwent [(18)F]
      fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Of 14 PD
      patients and all healthy controls PCASL-MRI could be obtained. Data were analyzed
      using scaled subprofile model/principal component analysis (SSM/PCA). RESULTS:
      Unique Parkinson's disease-related perfusion and metabolic covariance patterns
      were identified using PCASL and FDG-PET in the same patients. The PD-related
      metabolic covariance brain pattern is in high accordance with previously reports.
      Also our disease-related perfusion pattern is comparable to the earlier described
      perfusion pattern. The most marked difference between our perfusion and metabolic
      patterns is the larger perfusion decrease in cortical regions including the
      insula. CONCLUSION: We identified PD-related perfusion and metabolic brain
      patterns using PCASL and FDG-PET in the same patients which were comparable with
      results of existing research. In this respect, PCASL appears to be a promising
      addition in the early diagnosis of individual parkinsonian patients.

PMID- 25068114
TI  - Multi-investigator letter on reproducibility of neonatal heart regeneration
      following apical resection.

PMID- 25068115
TI  - Comment on "Do neonatal mouse hearts regenerate following heart apex resection"?

PMID- 25068116
TI  - Response to Sadek et al. and Kotlikoff et al.

PMID- 25068118
TI  - Sustained ERK activation underlies reprogramming in regeneration-competent
      salamander cells and distinguishes them from their mammalian counterparts.
AB  - In regeneration-competent vertebrates, such as salamanders, regeneration depends
      on the ability of various differentiated adult cell types to undergo natural
      reprogramming. This ability is rarely observed in regeneration-incompetent
      species such as mammals, providing an explanation for their poor regenerative
      potential. To date, little is known about the molecular mechanisms mediating
      natural reprogramming during regeneration. Here, we have identified the extent of
      extracellular signal-regulated kinase (ERK) activation as a key component of such
      mechanisms. We show that sustained ERK activation following serum induction is
      required for re-entry into the cell cycle of postmitotic salamander muscle cells,
      partially by promoting the downregulation of p53 activity. Moreover, ERK
      activation induces epigenetic modifications and downregulation of muscle-specific
      genes such as Sox6. Remarkably, while long-term ERK activation is found in
      salamander myotubes, only transient activation is seen in their mammalian
      counterparts, suggesting that the extent of ERK activation could underlie
      differences in regenerative competence between species. 

PMID- 25068117
TI  - Comparable generation of activin-induced definitive endoderm via additive Wnt or
      BMP signaling in absence of serum.
AB  - There is considerable interest in differentiating human pluripotent stem cells
      (hPSCs) into definitive endoderm (DE) and pancreatic cells for in vitro disease
      modeling and cell replacement therapy. Numerous protocols use fetal bovine serum,
      which contains poorly defined factors to induce DE formation. Here, we compared
      Wnt and BMP in their ability to cooperate with Activin signaling to promote DE
      formation in a chemically defined medium. Varying concentrations of WNT3A,
      glycogen synthase kinase (GSK)-3 inhibitors CHIR99021 and 6-bromoindirubin-3'
      oxime (BIO), and BMP4 could independently co-operate with Activin to effectively
      induce DE formation even in the absence of serum. Overall, CHIR99021 is favored
      due to its cost effectiveness. Surprisingly, WNT3A was ineffective in suppressing
      E-CADHERIN/CDH1 and pluripotency factor gene expression unlike GSK-3 inhibitors
      or BMP4. Our findings indicate that both Wnt and BMP effectively synergize with
      Activin signaling to generate DE from hPSCs, although WNT3A requires additional
      factors to suppress the pluripotency program inherent in hPSCs. 

PMID- 25068119
TI  - Wilms' tumor blastemal stem cells dedifferentiate to propagate the tumor bulk.
AB  - An open question remains in cancer stem cell (CSC) biology whether CSCs are by
      definition at the top of the differentiation hierarchy of the tumor. Wilms' tumor
      (WT), composed of blastema and differentiated renal elements resembling the
      nephrogenic zone of the developing kidney, is a valuable model for studying this
      question because early kidney differentiation is well characterized. WT neural
      cell adhesion molecule 1-positive (NCAM1(+)) aldehyde dehydrogenase 1-positive
      (ALDH1(+)) CSCs have been recently isolated and shown to harbor early renal
      progenitor traits. Herein, by generating pure blastema WT xenografts, composed
      solely of cells expressing the renal developmental markers SIX2 and NCAM1, we
      surprisingly show that sorted ALDH1(+) WT CSCs do not correspond to earliest
      renal stem cells. Rather, gene expression and proteomic comparative analyses
      disclose a cell type skewed more toward epithelial differentiation than the bulk
      of the blastema. Thus, WT CSCs are likely to dedifferentiate to propagate WT
      blastema. 

PMID- 25068120
TI  - Cytokine-regulated GADD45G induces differentiation and lineage selection in
      hematopoietic stem cells.
AB  - The balance of self-renewal and differentiation in long-term repopulating
      hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood
      homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce
      differentiation in LT-HSCs; however, the molecular mechanism orchestrating this
      delicate balance requires further elucidation. We identified the tumor suppressor
      GADD45G as an instructor of LT-HSC differentiation under the control of
      differentiation-promoting cytokine receptor signaling. GADD45G immediately
      induces and accelerates differentiation in LT-HSCs and overrides the self-renewal
      program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the
      absence of GADD45G enhances the self-renewal potential of LT-HSCs.
      Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is
      expressed, the development of LT-HSCs into lineage-committed progeny occurred
      within 36 hr and uncovered a selective lineage choice with a severe reduction in
      megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G
      as a central molecular linker of extrinsic cytokine differentiation and lineage
      choice control in hematopoiesis. 

PMID- 25068121
TI  - Aging-like phenotype and defective lineage specification in SIRT1-deleted
      hematopoietic stem and progenitor cells.
AB  - Aging hematopoietic stem cells (HSCs) exhibit defective lineage specification
      that is thought to be central to increased incidence of myeloid malignancies and
      compromised immune competence in the elderly. Mechanisms underlying these age
      related defects remain largely unknown. We show that the deacetylase Sirtuin
      (SIRT)1 is required for homeostatic HSC maintenance. Differentiation of young
      SIRT1-deleted HSCs is skewed toward myeloid lineage associated with a significant
      decline in the lymphoid compartment, anemia, and altered expression of associated
      genes. Combined with HSC accumulation of damaged DNA and expression patterns of
      age-linked molecules, these have striking overlaps with aged HSCs. We further
      show that SIRT1 controls HSC homeostasis via the longevity transcription factor
      FOXO3. These findings suggest that SIRT1 is essential for HSC homeostasis and
      lineage specification. They also indicate that SIRT1 might contribute to delaying
      HSC aging. 

PMID- 25068122
TI  - Actin cytoskeletal disruption following cryopreservation alters the
      biodistribution of human mesenchymal stromal cells in vivo.
AB  - Mesenchymal stromal cells have shown clinical promise; however, variations in
      treatment responses are an ongoing concern. We previously demonstrated that MSCs
      are functionally stunned after thawing. Here, we investigated whether this
      cryopreservation/thawing defect also impacts the postinfusion biodistribution
      properties of MSCs. Under both static and physiologic flow, compared with live
      MSCs in active culture, MSCs thawed from cryopreservation bound poorly to
      fibronectin (40% reduction) and human endothelial cells (80% reduction),
      respectively. This reduction correlated with a reduced cytoskeletal F-actin
      content in post-thaw MSCs (60% reduction). In vivo, live human MSCs could be
      detected in murine lung tissues for up to 24 hr, whereas thawed MSCs were
      undetectable. Similarly, live MSCs whose actin cytoskeleton was chemically
      disrupted were undetectable at 24 hr postinfusion. Our data suggest that post
      thaw cryopreserved MSCs are distinct from live MSCs. This distinction could
      significantly affect the utility of MSCs as a cellular therapeutic. 

PMID- 25068123
TI  - Mechanisms for interferon-alpha-induced depression and neural stem cell
      dysfunction.
AB  - New neurons generated by the neural stem cells (NSCs) in the adult hippocampus
      play an important role in emotional regulation and respond to the action of
      antidepressants. Depression is a common and serious side effect of interferon
      alpha (IFN-alpha), which limits its use as an antiviral and antitumor drug.
      However, the mechanism(s) underlying IFN-induced depression are largely unknown.
      Using a comprehensive battery of behavioral tests, we found that mice subjected
      to IFN-alpha treatment exhibited a depression-like phenotype. IFN-alpha directly
      suppressed NSC proliferation, resulting in the reduced generation of new neurons.
      Brain-specific mouse knockout of the IFN-alpha receptor prevented IFN-alpha
      induced depressive behavioral phenotypes and the inhibition of neurogenesis,
      suggesting that IFN-alpha suppresses hippocampal neurogenesis and induces
      depression via its receptor in the brain. These findings provide insight for
      understanding the neuropathology underlying IFN-alpha-induced depression and for
      developing new strategies for the prevention and treatment of IFN-alpha-induced
      depressive effects. 

PMID- 25068124
TI  - Direct genesis of functional rodent and human schwann cells from skin mesenchymal
      precursors.
AB  - Recent reports of directed reprogramming have raised questions about the
      stability of cell lineages. Here, we have addressed this issue, focusing upon
      skin-derived precursors (SKPs), a dermally derived precursor cell. We show by
      lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and
      not neural crest-derived cells. These mesenchymally derived SKPs can, without
      genetic manipulation, generate functional Schwann cells, a neural crest cell
      type, and are highly similar at the transcriptional level to Schwann cells
      isolated from the peripheral nerve. This is not a mouse-specific phenomenon,
      since human SKPs that are highly similar at the transcriptome level can be made
      from neural crest-derived facial and mesodermally derived foreskin dermis and the
      foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived
      mesenchymal precursors can differentiate into bona fide peripheral glia in the
      absence of genetic manipulation, suggesting that developmentally defined lineage
      boundaries are more flexible than widely thought. 

PMID- 25068125
TI  - Neurovascular recovery via co-transplanted neural and vascular progenitors leads
      to improved functional restoration after ischemic stroke in rats.
AB  - The concept of the "neurovascular unit," emphasizing the interactions between
      neural and vascular components in the brain, raised the notion that neural
      progenitor cell (NPC) transplantation therapy aimed at neural repair may be
      insufficient for the treatment of ischemic stroke. Here, we demonstrate that
      enhanced neurovascular recovery via cotransplantation of NPCs and embryonic stem
      cell-derived vascular progenitor cells (VPCs) in a rat stroke model is correlated
      with improved functional recovery after stroke. We found that cotransplantation
      promoted the survival, migration, differentiation, and maturation of neuronal and
      vascular cells derived from the cotransplanted progenitors. Furthermore, it
      triggered an increased generation of VEGF-, BDNF-, and IGF1-expressing neural
      cells derived from the grafted NPCs. Consistently, compared with transplantation
      of NPCs alone, cotransplantation more effectively improved the neurobehavioral
      deficits and attenuated the infarct volume. Thus, cotransplantation of NPCs and
      VPCs represents a more effective therapeutic strategy for the treatment of stroke
      than transplantation of NPCs alone. 

PMID- 25068126
TI  - Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE
      model of multiple sclerosis.
AB  - Current therapies for multiple sclerosis (MS) are largely palliative, not
      curative. Mesenchymal stem cells (MSCs) harbor regenerative and immunosuppressive
      functions, indicating a potential therapy for MS, yet the variability and low
      potency of MSCs from adult sources hinder their therapeutic potential. MSCs
      derived from human embryonic stem cells (hES-MSCs) may be better suited for
      clinical treatment of MS because of their unlimited and stable supply. Here, we
      show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal
      demyelination in a mouse experimental autoimmune encephalitis (EAE) model of MS,
      and that the EAE disease-modifying effect of hES-MSCs is significantly greater
      than that of human bone-marrow-derived MSCs (BM-MSCs). Our evidence also suggests
      that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE
      therapeutic activity of these cells. A distinct ability to extravasate and
      migrate into inflamed CNS tissues may also be associated with the robust
      therapeutic effects of hES-MSCs on EAE. 

PMID- 25068127
TI  - Functional and pharmacological analysis of cardiomyocytes differentiated from
      human peripheral blood mononuclear-derived pluripotent stem cells.
AB  - Advances in induced pluripotent stem cell (iPSC) technology have set the stage
      for routine derivation of patient- and disease-specific human iPSC-cardiomyocyte
      (CM) models for preclinical drug screening and personalized medicine approaches.
      Peripheral blood mononuclear cells (PBMCs) are an advantageous source of somatic
      cells because they are easily obtained and readily amenable to transduction.
      Here, we report that the electrophysiological properties and pharmacological
      responses of PBMC-derived iPSC CM are generally similar to those of iPSC CM
      derived from other somatic cells, using patch-clamp, calcium transient, and
      multielectrode array (MEA) analyses. Distinct iPSC lines derived from a single
      patient display similar electrophysiological features and pharmacological
      responses. Finally, we demonstrate that human iPSC CMs undergo acute changes in
      calcium-handling properties and gene expression in response to rapid electrical
      stimulation, laying the foundation for an in-vitro-tachypacing model system for
      the study of human tachyarrhythmias. 

PMID- 25068128
TI  - Time-lapse analysis of human embryonic stem cells reveals multiple bottlenecks
      restricting colony formation and their relief upon culture adaptation.
AB  - Using time-lapse imaging, we have identified a series of bottlenecks that
      restrict growth of early-passage human embryonic stem cells (hESCs) and that are
      relieved by karyotypically abnormal variants that are selected by prolonged
      culture. Only a minority of karyotypically normal cells divided after plating,
      and these were mainly cells in the later stages of cell cycle at the time of
      plating. Furthermore, the daughter cells showed a continued pattern of cell death
      after division, so that few formed long-term proliferating colonies. These colony
      forming cells showed distinct patterns of cell movement. Increasing cell density
      enhanced cell movement facilitating cell:cell contact, which resulted in
      increased proportion of dividing cells and improved survival postplating of
      normal hESCs. In contrast, most of the karyotypically abnormal cells reentered
      the cell cycle on plating and gave rise to healthy progeny, without the need for
      cell:cell contacts and independent of their motility patterns. 

PMID- 25068129
TI  - Local BMP-SMAD1 signaling increases LIF receptor-dependent STAT3 responsiveness
      and primed-to-naive mouse pluripotent stem cell conversion frequency.
AB  - Conversion of EpiSCs to naive ESCs is a rare event that is driven by the
      reestablishment of the naive transcription factor network. In mice, STAT3
      activation is sufficient to drive conversion of EpiSCs to the naive pluripotent
      stem cell (PSC) state. However, the lack of responsiveness of EpiSCs to LIF
      presents a bottleneck in this conversion process. Here, we demonstrate that local
      accumulation of BMP-SMAD1 signaling, in cooperation with GP130 ligands, enhances
      the recovery of LIF responsiveness by directly controlling transcription of the
      LIF receptor (Lif-r). Addition of BMP and LIF to EpiSCs increases both LIF
      responsiveness and conversion frequencies to naive PSCs. Mechanistically, we show
      that the transcriptional cofactor P300 plays a critical role by mediating complex
      formation between STAT3 and SMAD1. This demonstration of how the local
      microenvironment or stem cell niche reactivates dormant signaling responsiveness
      and developmental potential may be applicable to other stem cell niche-containing
      systems. 

PMID- 25068130
TI  - A method to identify and isolate pluripotent human stem cells and mouse epiblast
      stem cells using lipid body-associated retinyl ester fluorescence.
AB  - We describe the use of a characteristic blue fluorescence to identify and isolate
      pluripotent human embryonic stem cells and human-induced pluripotent stem cells.
      The blue fluorescence emission (450-500 nm) is readily observed by fluorescence
      microscopy and correlates with the expression of pluripotency markers (OCT4,
      SOX2, and NANOG). It allows easy identification and isolation of undifferentiated
      human pluripotent stem cells, high-throughput fluorescence sorting and subsequent
      propagation. The fluorescence appears early during somatic reprogramming. We show
      that the blue fluorescence arises from the sequestration of retinyl esters in
      cytoplasmic lipid bodies. The retinoid-sequestering lipid bodies are specific to
      human and mouse pluripotent stem cells of the primed or epiblast-like state and
      absent in naive mouse embryonic stem cells. Retinol, present in widely used stem
      cell culture media, is sequestered as retinyl ester specifically by primed
      pluripotent cells and also can induce the formation of these lipid bodies. 

PMID- 25068131
TI  - A human pluripotent stem cell surface N-glycoproteome resource reveals markers,
      extracellular epitopes, and drug targets.
AB  - Detailed knowledge of cell-surface proteins for isolating well-defined
      populations of human pluripotent stem cells (hPSCs) would significantly enhance
      their characterization and translational potential. Through a chemoproteomic
      approach, we developed a cell-surface proteome inventory containing 496 N-linked
      glycoproteins on human embryonic (hESCs) and induced PSCs (hiPSCs). Against a
      backdrop of human fibroblasts and 50 other cell types, >100 surface proteins of
      interest for hPSCs were revealed. The >30 positive and negative markers verified
      here by orthogonal approaches provide experimental justification for the rational
      selection of pluripotency and lineage markers, epitopes for cell isolation, and
      reagents for the characterization of putative hiPSC lines. Comparative
      differences between the chemoproteomic-defined surfaceome and the transcriptome
      predicted surfaceome directly led to the discovery that STF-31, a reported GLUT-1
      inhibitor, is toxic to hPSCs and efficient for selective elimination of hPSCs
      from mixed cultures. 

PMID- 25068132
TI  - Modulating innate immunity improves hepatitis C virus infection and replication
      in stem cell-derived hepatocytes.
AB  - In this study, human embryonic stem cell-derived hepatocytes (hESC-Heps) were
      investigated for their ability to support hepatitis C virus (HCV) infection and
      replication. hESC-Heps were capable of supporting the full viral life cycle,
      including the release of infectious virions. Although supportive, hESC-Hep viral
      infection levels were not as great as those observed in Huh7 cells. We reasoned
      that innate immune responses in hESC-Heps may lead to the low level of infection
      and replication. Upon further investigation, we identified a strong type III
      interferon response in hESC-Heps that was triggered by HCV. Interestingly,
      specific inhibition of the JAK/STAT signaling pathway led to an increase in HCV
      infection and replication in hESC-Heps. Of note, the interferon response was not
      evident in Huh7 cells. In summary, we have established a robust cell-based system
      that allows the in-depth study of virus-host interactions in vitro. 

PMID- 25068136
TI  - Omega-3 and omega-6 content of medicinal foods for depressed patients:
      implications from the Iranian Traditional Medicine.
AB  - OBJECTIVES: Considering the increasing prevalence of depression in modern
      societies and the positive effects of omega-3 polyunsaturated fatty acids on
      depression, this study aims to investigate the omega-3 and omega-6 content of
      various foodstuffs, prescribed or prohibited by Iranian Traditional Medicine
      (ITM). MATERIALS AND METHODS: Firstly, reliable sources of Iranian Traditional
      Medicine were reviewed in order to identify the prescribed and prohibited
      foodstuffs for depressed patients. Afterwards, according to the online database
      of United States Department of Agriculture (URL:
      http://ndb.nal.usda.gov/ndb/search/list), the ratio of linoleic acid to alpha
      linolenic acid (as representatives of omega-6 and omega-3, respectively) was
      identified in each foodstuff. Finally, the ratios of omega-6 to omega-3 were
      compared between seven food groups of vegetables, fruits, dry goods, high protein
      products, dairies, breads, and spices. RESULTS: Based on the resources of Iranian
      Traditional Medicine, the following foods are prescribed for depressed patients:
      basil, coriander, spinach, lettuce, squash, peppermint, dill, chicory, celery,
      beet, quince, cucumber, watermelon, grape, peach, pomegranate, banana, apple,
      currant, pistachio, dried fig, almond, egg, chicken, lamb, trout, milk, bread
      without bran, saffron, oregano, and coriander seeds. On the other hand, cabbage,
      eggplant, onion, garlic, broad beans, lentils, beef, whole wheat bread, and
      mustard are prohibited. It should be noted that omega-3 content in some
      prescribed foods is more than that of the prohibited ones. CONCLUSION: The
      present study showed that mint, basil, spinach, lettuce, squash, lamb, saffron,
      oregano, cucumber, pistachio, milk, and also wild trout can be considered as
      medicinal foods for depressed patients.

PMID- 25068137
TI  - Phenolic and flavonoid content of Elaeagnus angustifolia L. (leaf and flower).
AB  - Objectives : Leaves and flowers of Elaeagnus angustifolia contain phenolic and
      flavonoid compounds. These compounds have antioxidant properties that protect
      cells from oxidative damage. The aim of this study was to determine and analyze
      total phenolic and flavonoid content of leaves and flowers in two E. angustifolia
      variants using different solvents (ethanol and methanol). MATERIALS AND METHODS:
      Ethanolic and methanolic extracts of the plant leaves and flowers were prepared.
      Experiments were carried out to measure their phenolic and flavonoid content
      using two solvents. Data were analyzed using Instat-N software. RESULTS: RESULTS
      showed that the amount of phenolic and flavonoid compounds in both ethanolic and
      methanolic extracts was higher in Fariman variant compared with Mashhad variant.
      Ethanolic and methanolic extracts of Fariman variant had the highest amount of
      phenolic compound (10.91+/-0.18, 10.28+/- 0.36 mg GAE/100gFW, respectively) and
      also the highest amounts of flavonoids (5.80+/-0.10, 3.36+/-0.05 mgQE/100gFW,
      respectively). Phenolic and flavonoids compounds were better extracted using
      methanol and ethanol solvent. CONCLUSIONS: In both varieties and solvents, the
      amount of phenolic and flavonoids compounds in leaves were higher than flowers.
      In addition, the phenolic and flavonoids compounds were higher in Fariman
      compared to Mashhad variants.

PMID- 25068138
TI  - Cosmetic ethnobotany practiced by tribal women of Kashmir Himalayas.
AB  - OBJECTIVE: Himalayan mountain populations have been dependent upon indigenous
      plant resources for their health care for many years. Tribal women are interested
      in use of local herbs for cosmetic purposes. The present work is based on the
      results of research conducted on cosmetic uses of some important plants by the
      tribal women in District Poonch, Azad Kashmir Pakistan. MATERIALS AND METHODS: An
      ethno botanical survey was carried out during summer 2012. The data were
      collected from 310 female informants from 16 villages using questionnaire method
      and semi structured interviews. RESULTS: A total of 39 plants species belonging
      to 20 families, being used for various cosmetic purposes were recorded.
      Indigenous species are traditionally used by the locals for problems including
      acne (16%), hair growth (11%), bad breath (12%), facial spots (9%), allergy,
      (9%), fairness (8%), wrinkles (8%), eye and lip care (9%). Seventy different
      recipes were recorded to be practiced by locals using herbal parts. The major
      plant parts utilized in herbal recipes included fruit (32.8%), Leaves (25.2%),
      seeds (13.4%) and roots (8.9%). Women of older (>30 years) age group showed
      greater (67%) response regarding knowledge and practice of cosmetic herbs.
      CONCLUSION: This study was the 1(st) ever project focusing on cosmetic
      perspectives of ethno-botany in the area. Our study contributes to an improved
      understanding of ignored aspect of cosmetic ethnobotany among the local women.
      Further detailed investigations are recommended to record and preserve precious
      ethno-botanical knowledge of the area.

PMID- 25068140
TI  - Identification, determination, and study of antioxidative activities of
      hesperetin and gallic acid in hydro-alcoholic extract from flowers of Eriobotrya
      japonica (Lindl.).
AB  - OBJECTIVES: Eriobotrya japonica belongs to the Rosaceae. Studies have shown that
      the flowers of this plant are rich in phenolic and flavonoid compounds.
      Accorrdingly, the evaluation of antioxidative effects of Eriobotrya japonica
      Flower Extract (EJFE) have been performed in vitro. MATERIAL AND METHODS: In this
      study, to investigate the influences of components of EJFE on its antioxidative
      activity, extract was prepared using hydro-alcoholic (25:75 V/V) solvent and the
      antioxidative activity of the extract was evaluated based on the scavenging of
      various radicals (DPPH and H2O2) by spectrophotometric method and chelating of
      ferrous ions by ferrozine reagent. RESULTS: HPLC analysis of the Eriobotrya
      japonica Flower Extract (EJFE) revealed hesperetin and gallic acid as the major
      antioxidants. When the content of total flavonoid and polyphenolic compounds in
      the flower extract of this plant was examined, a significantly higher level of
      total polyphenols was found in Eriobotrya japonica flower extract. CONCLUSION:
      RESULTS demonstrate that the high ability to scavenge free radicals, reducing
      power, and Fe(+2)chelating activity exerted by the EJFE were due to the high
      content of hesperetin and gallic acid in the flowers.

PMID- 25068139
TI  - The role for nitric oxide on the effects of hydroalcoholic extract of Achillea
      wilhelmsii on seizure.
AB  - Objective : Nitric oxide (NO) plays an important role both as a consequence and
      as a cause of epileptic seizures. Regarding the central nervous system depressant
      effects of Achillea wilhelmsii (A. wilhelmsii), as well the effects of the plant
      on NO, this study was aimed to elucidate the possible role for nitric oxide on
      the effects of hydroalcoholic extract of A. wilhelmsii on pentylenetetrazole
      (PTZ)-induced seizures. MATERIALS AND METHODS: Fifty-six male Wistar rats were
      divided into 7 groups (n=8 in each group) and treated with (1) normal saline, (2)
      normal saline before pentylenetetrazole (PTZ, 90 mg/kg), (3-7) A. wilhelmsii
      extract (100, 200, 400, 800, and 1200 mg/kg) before PTZ. Latency to first minimal
      colonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) as
      well as the mortality rate were recorded. The brain tissues were then removed for
      biochemical measurements. Fisher's exact probability test as well as analysis of
      variance (ANOVA), followed by Tukey's test were used for statistical evaluation.
      RESULTS: Treatment with 100- 1200 mg/kg of the extract did not affect MCS
      latencies. 400 mg/kg of the extract prolonged GTCS latency (p<0.001), however,
      the lower and higher doses were not effective. Nitric oxide metabolites
      concentrations in the hippocampal tissues of the animals treated with 100, 200,
      and 400 mg/kg of the extract were increased compared with saline (p<0.05-p<0.01).
      CONCLUSION: The present study showed that hydroalcoholic extract of A. wilhelmsii
      affects NO metabolites in brain tissues as well the severity of seizures in PTZ
      induced seizure model.

PMID- 25068141
TI  - Moderate dose of watercress and red radish does not reduce oxygen consumption
      during graded exhaustive exercise.
AB  - OBJECTIVE: Very recent studies have reported positive effects of dietary nitrate
      on the oxygen consumption during exercise. This research aimed to study the
      effect of moderate dose of high-nitrate vegetables, watercress (Nasturtium
      officinale) and red radish (Raphanus sativus) compared with a control group on
      the incremental treadmill exercise test following a standard Bruce protocol
      controlled by computer. MATERIALS AND METHODS: Group 1 consumed 100 g watercress
      (n=11, 109.5 mg nitrate/day), and group 2 consumed 100 g red radish (n=11, mg
      173.2 mg nitrate/day) for seven days, and control group (n=14) was prohibited
      from high nitrate intake. RESULTS: During exercise, watercress group showed
      significant changes in the maximum values of Respiratory Exchange Ratio (RER)
      (p<0.05), End-Tidal O2 Fraction (FETO2) (p<0.05), and energy consumption from
      carbohydrate (p<0.01). Red radish group had a significant increase in the VCO2
      (p<0.01), RER (p<0.01), VT (p<0.05), VCO2/kg (p<0.05), and energy consumption
      from carbohydrates (p<0.01). When all groups in the same workload were normalized
      by the subject's body mass, watercress had a significant increase in the total
      expired CO2 (p<0.05), RER (p<0.05), FETO2 (p<0.05), and energy consumption from
      carbohydrates (p<0.05) compared with the control group. Similar comparison
      between red radish and control group revealed a significant increase during pre
      test in the total CO2 production (p<0.05), VCO2 (p<0.05), RER (p<0.01), VT
      (p<0.05), and VCO2/kg (p<0.05). Conclusion : Current results indicate higher
      carbon dioxide production in the experimental groups in the same workload. This
      might have a negative impact on the exercise performance. Further investigations
      with controlled exercise program will be necessary.

PMID- 25068142
TI  - Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats
      treated with lamotrigine.
AB  - OBJECTIVE: Lamotrigine is an antiepileptic drug, widely used in the treatment of
      epilepsy; long-term use of this drug can cause hepatotoxicity. Zingiber
      officinale Roscoe (ginger) possesses antioxidant properties. In present research,
      the effect ofhydroalcoholic extract of ginger (HEG) on the liver of lamotrigine
      treated epileptic rats was investigated Material and Methods: Forty-eight female
      Wistar rats were selected and allocated to 8 groups of 6 each. Group 1: Negative
      controls were treated with normal saline. Group 2: Positive controls were treated
      with lamotrigine (LTG) (10 mg/kg) daily by gavages for 4 consecutive weeks.
      Epilepsy was induced in treatment groups by i.p. injection of pentylenetetrazol
      (PTZ) (40 mg/kg). Group 3: Epileptic group received normal saline (10 ml/kg).
      Group 4: Epileptic group was treated with LTG (10 mg/kg). Groups 5 and 6:
      Epileptic groups received HEG (50 and 100 mg/kg). Groups 7 and 8: Epileptic
      groups received LTG and HEG (50 and 100 mg/kg). At the end of 28 days, blood
      samples were drawn and their livers were processed for light microscopy. RESULTS:
      The mean values of TG, CHOL, AST, and ALT activity significantly rose (p<0.01) in
      groups 2, 3, and 4, while in rats treated with HEG (groups 5, 6, 7, and 8), the
      levels of liver enzymes significantly decreased (p<0.05) compared with epileptic
      group treated with lamotrigine (group 4). Histopathological changes of liver
      samples were comparable with respective control. CONCLUSION: These results
      suggest that hydroalcoholic extract of ginger improves liver function in
      lamotrigine-induced hepatotoxicity.

PMID- 25068143
TI  - Evaluation of analgesic, anti-inflammatory and CNS depressant activities of
      methanolic extract of Lawsonia inermis barks in mice.
AB  - OBJECTIVES: The study was carried out to assess the analgesic, anti-inflammatory,
      and CNS depressant activity of the methanolic extract of the Lawsonia inermis
      barks (MELIB). MATERIALS AND METHODS: Anti-inflammatory effects of MEBLI were
      studied using carrageenan-induced inflammatory method at the dose of 300 and 500
      mg/kg b.wt., p.o. Analgesic activity was measured using acetic acid-induced
      writhing model and formalin-induced licking and biting in mice. The CNS
      depressant activity was evaluated by observing the reduction of locomotor and
      exploratory activities in the open field and hole cross tests at a dose of 300
      and 500 mg/kg body weight. RESULTS: Statistical analysis showed that dose of 500
      mg/kg exhibited higher analgesic activity against acetic acid-induced pain in
      mice than the standard drug diclofenac sodium. Furthermore, doses of 300 and 500
      mg/kg caused higher percent of protection (91.16% and 95.03%, respectively) of
      licking and biting of formalin-induced mice than diclophenac sodium (70.72%). The
      Lawsonia inemis methanolic extract (300 and 500 mg/kg) also exhibited sustained
      inhibition (54.97% and 65.56%) of paw edema at the 4(th) hour compared with
      standard indomethacin (74.17%). Besides, the plant extract also had significant
      (p<0.05) dose-dependent CNS depressant activity. CONCLUSION: this study
      recommends that the methanolic extract of Lawsonia inermis barks has significant
      analgesic, anti-inflammatory, and CNS depressant properties.

PMID- 25068144
TI  - Post cardiac surgery acute kidney injury: a woebegone status rejuvenated by the
      novel biomarkers.
AB  - BACKGROUND: Acute kidney injury (AKI) is common after cardiac surgery, the
      incidence varying between 7.7% and 28.1%. It significantly increases morbidity
      and mortality. Creatinine considerably delays the diagnosis with its own attended
      demerits. Novel urinary biomarkers are emerging which help in rapid diagnosis
      thus reducing the morbidity and mortality. Biomarkers of our study were
      neutrophil gelatinase-associated lipocalin (NGAL) and Interleukin-18 (IL-18).
      OBJECTIVES: To find out the incidence of AKI in post-cardiac surgery patients in
      our hospital, the ability of the two biomarkers in early diagnosis in predicting
      the severity of AKI based on RIFLE's criteria and their ability to discriminate
      pre-renal from intrinsic AKI. PATIENTS AND METHODS: One-hundred patients who
      underwent cardiac surgery were selected. Midstream urine samples were collected
      at 3 time intervals (baseline before surgery, 24 hours and 7 days after surgery).
      Biomarkers were measured by ELISA using BIORAD processors. Fractional excretion
      of sodium and urea were used to discriminate pre-renal from intrinsic AKI.
      RESULTS: Out of 100 patients, 31 had AKI, 11 being pre-renal and 20 intrinsic
      AKI. Four patients required renal replacement therapy (12.9% among AKI cases and
      4% in the overall study cohort). Four among 31 expired in intensive care unit.
      Identifiable risk factors for AKI included insulin requiring diabetes mellitus,
      chronic obstructive pulmonary disease, increased cardio-pulmonary bypass time,
      combined valvular surgery and coronary artery bypass grafting, employment of
      intra-aortic balloon counter pulsation, left main coronary artery occlusion and
      an ejection fraction of < 40%. NGAL was extremely sensitive (area under curve
      0.96) in detecting intrinsic AKI at 24 hours followed by IL-18 ratio with an area
      under curve of 0.89. Creatinine at 24 hours was able to detect only 31.6% of
      intrinsic AKI. None of the pre-renal cases showed rise in the urinary biomarker
      levels. Patients with higher stages of AKI had higher levels of both biomarkers
      than those at lower stages. CONCLUSIONS: NGAL and IL-18 obviated the
      disadvantages of creatinine. They were efficient in early detection of AKI, in
      differentiating pre-renal from intrinsic AKI and in predicting the severity of
      AKI reliably in post-cardiac surgery patients.

PMID- 25068146
TI  - Intestinal Co-infection of Tuberculosis and CMV can Cause Massive Lower GI
      Bleeding in a Patient with HIV.
AB  - Tuberculosis (TB) and HIV are considered pandemic by the World Health
      Organization (WHO). It has been reported that HIV infection is one of the major
      risk factors for the development of TB, increasing the incidence by up to 1,000
      times, but it often has an atypical presentation. The incidence of extrapulmonary
      TB is increasing, largely among HIV patients. The diagnosis of intestinal TB is a
      challenge because of its chronic and nonspecific presentation which often mimics
      other diseases, and requires a high clinical suspicion to timely diagnose.
      Massive lower gastrointestinal bleeding due to intestinal TB was once an uncommon
      complication of TB, but recent reports indicate an increased incidence especially
      in developing countries. We suspect that co-infection with cytomegalovirus
      colitis contributes to the massive hemorrhage from intestinal TB. Surgical
      intervention is the recommended management for intestinal TB complicated by lower
      gastrointestinal bleeding. Accordingly, it is important for HIV patients to be
      screened and treated for TB to prevent this complication. Although the diagnosis
      is a challenge, it is important to consider intestinal TB as a cause of
      gastrointestinal bleeding in the HIV positive patients.

PMID- 25068147
TI  - Towards single-cell LC-MS phosphoproteomics.
AB  - Protein phosphorylation is a ubiquitous posttranslational modification, which is
      heavily involved in signal transduction. Misregulation of protein phosphorylation
      is often associated with a decrease in cell viability and complex diseases such
      as cancer. The dynamic and low abundant nature of phosphorylated proteins makes
      studying phosphoproteome a challenging task. In this review, we summarize state
      of the art proteomic techniques to study and quantify peptide phosphorylation in
      biological systems and discuss their limitations. Due to its short-lived nature,
      the phosphorylation event cannot be precisely traced in a heterogonous cell
      population, which highlights the importance of analyzing phosphorylation events
      at the single cell level. Mainly, we focus on the methodical and instrumental
      developments in proteomics and nanotechnology, which will help to build more
      accurate and robust systems for the feasibility of phosphorylation analysis at
      the single cell level. We propose that an automated and miniaturized construction
      of analytical systems holds the key to the future of phosphoproteomics;
      therefore, we highlight the benchmark studies in this direction. Having advanced
      and automated microfluidic chip LC systems will allow us to analyze single-cell
      phosphoproteomics and quantitatively compare it with others. The progress in the
      microfluidic chip LC systems and feasibility of the single-cell phosphoproteomics
      will be beneficial for early diagnosis and detection of the treatment response of
      many crucial diseases. 

PMID- 25068145
TI  - Marmosets as a preclinical model for testing "off-label" use of doxycycline to
      turn on Flt3L expression from high-capacity adenovirus vectors.
AB  - We developed a combined conditional cytotoxic, i.e., herpes simplex type 1
      thymidine kinase (TK), plus immune-stimulatory, i.e., fms-like tyrosine kinase
      ligand-3-mediated gene therapy for glioblastoma multiforme (GBM). Therapeutic
      transgenes were encoded within high-capacity adenoviral vectors (HC-Ad); TK was
      expressed constitutively, while Flt3L was under the control of the TetOn
      regulatable promoter. We previously assessed efficacy and safety in intracranial
      GBM rodent models. But, since this approach involves expression of a cytokine
      within the brain, we chose the nonhuman primate, i.e., Callithrix jaccus
      (marmoset) as it has been established that its immune response shares
      similarities with man. We characterized the safety, cell-type specific
      expression, and doxycycline (DOX)-inducibility of HC-Ad-TetOn-Flt3L delivered
      within the striatum. We used allometrically scaled DOX doses delivered orally,
      twice daily for one month, mimicking the route and duration of DOX administration
      planned for the GBM trial. Flt3L was effectively expressed within astrocytes,
      microglia, oligodendrocytes, and neurons. No evidence of brain or systemic
      toxicities due to the treatment was encountered. Our data indicate that DOX doses
      equivalent to those used in humans to treat infections can be safely used "off
      label" to turn "on" therapeutic gene expression from HC-Ad-TetOn-Flt3L; providing
      evidence for the safety of this approach in the clinic.

PMID- 25068148
TI  - Petroleomics by electrospray ionization FT-ICR mass spectrometry coupled to
      partial least squares with variable selection methods: prediction of the total
      acid number of crude oils.
AB  - Negative-ion mode electrospray ionization, ESI(-), with Fourier transform ion
      cyclotron resonance mass spectrometry (FT-ICR MS) was coupled to a Partial Least
      Squares (PLS) regression and variable selection methods to estimate the total
      acid number (TAN) of Brazilian crude oil samples. Generally, ESI(-)-FT-ICR mass
      spectra present a power of resolution of ca. 500,000 and a mass accuracy less
      than 1 ppm, producing a data matrix containing over 5700 variables per sample.
      These variables correspond to heteroatom-containing species detected as
      deprotonated molecules, [M - H](-) ions, which are identified primarily as
      naphthenic acids, phenols and carbazole analog species. The TAN values for all
      samples ranged from 0.06 to 3.61 mg of KOH g(-1). To facilitate the spectral
      interpretation, three methods of variable selection were studied: variable
      importance in the projection (VIP), interval partial least squares (iPLS) and
      elimination of uninformative variables (UVE). The UVE method seems to be more
      appropriate for selecting important variables, reducing the dimension of the
      variables to 183 and producing a root mean square error of prediction of 0.32 mg
      of KOH g(-1). By reducing the size of the data, it was possible to relate the
      selected variables with their corresponding molecular formulas, thus identifying
      the main chemical species responsible for the TAN values.

PMID- 25068149
TI  - A multi-scale approach of the mechanisms underlying exopolysaccharide auto
      organization in the Proteus mirabilis extracellular matrix.
AB  - For decades, the origin of the concentric ring pattern of bacterial swarming
      colonies has puzzled microbiologists. It was hypothesized that a periodic water
      activity variation originates a phase transition within the extracellular matrix
      water H bond network, which switches on and off the exopolysaccharide auto
      organization. Both rheological and infrared spectroscopy measurements
      respectively performed at a molecular scale and on a currently migrating colony,
      have given a physical insight into the mechanisms which underlie the switch
      between swarming and consolidation phases. Thanks to in situ and real time
      infrared microspectroscopy, and thanks to the brilliance of the infrared beam at
      SOLEIL synchrotron, here we demonstrate that Proteus mirabilis swarming is
      triggered by a periodic variation of water activity at the colony edge. A dynamic
      behavior emerges from the global properties of the multicellular entity which
      relies on the ability of the bacterial cells to tune exoproduct synthesis in
      order to undergo sharp transitions at a given water activity threshold. 

PMID- 25068150
TI  - Sample preparation for mass spectrometric analysis of human serum N-glycans using
      hydrophilic interaction chromatography-based solid phase extraction.
AB  - Expression levels of N-linked glycans derived from human serum glycoproteins have
      been shown to change during the progression of many diseases. Generally, N
      glycans released from human serum proteins co-exist with endogenous serum
      peptides, salts, and other contaminants. Effective removal of these contaminants
      is essential to obtain the glycan profile of human serum proteins. Here, we
      developed a sample preparation method for mass spectrometry (MS) analysis of N
      linked glycans derived from human serum glycoproteins based on a zwitterionic
      hydrophilic material named Click TE-Cys. The high hydrophilicity of Click TE-Cys,
      resulting from its unique surface structure and charge distribution, facilitated
      removal of co-existing salts and endogenous serum peptides. Furthermore, the
      present enrichment approach was handled in parallel, thus saving time. Using this
      method, a total of 47 unique N-glycans released from human serum proteins were
      identified. The intrabatch and interbatch coefficients of variation for the 47 N
      linked glycans were 8.57% +/- 0.96% and 9.22% +/- 1.03%, respectively. These
      results demonstrate that the present method is suitable for fast purification of
      N-linked glycans derived from human serum glycoproteins, and has potential for
      clinical application. 

PMID- 25068151
TI  - Strip biosensor for amplified detection of nerve growth factor-beta based on a
      molecular translator and catalytic DNA circuit.
AB  - We have demonstrated a new visual detection approach based on a molecular
      translator and a catalytic DNA circuit for the detection of nerve growth factor
      beta (NGF-beta). In this assay, a molecular translator based on the binding
      induced DNA strand-displacement reaction was employed to convert the input
      protein to an output DNA signal. The molecular translator is composed of a target
      recognition element and a signal output element. Target recognition is achieved
      by the binding of the anti-NGF-beta antibody to the target protein. Polyclonal
      anti-NGF-beta antibody is conjugated to DNA1 and DNA2. The antibody conjugated
      DNA1 is initially hybridized to DNA3 to form a stable DNA1/DNA3 duplex. In the
      presence of NGF-beta, the binding of the same target protein brings DNA1 and DNA2
      into close proximity, resulting in an increase in their local effective
      concentration. This process triggers the strand-displacement reaction between
      DNA2 and DNA3 and releases the output DNA3. The released DNA3 is further
      amplified by a catalytic DNA circuit. The product of the catalytic DNA circuit is
      detected by a strip biosensor. This proposed assay has high sensitivity and
      selectivity with a dynamic response ranging from 10 fM to 10 pM, and its
      detection limit is 10 fM of NGF-beta. This work provides a sensitive, enzyme
      free, and universal strategy for the detection of other proteins. 

PMID- 25068152
TI  - A pillar[5]arene and crown ether fused bicyclic host: synthesis, guest
      discrimination and simultaneous binding of two guests with different shapes,
      sizes and electronic constitutions.
AB  - A bicyclic host molecule 1 consisting of a pillar[5]arene and a 1,5
      dioxynaphthalene-based crown ether unit has been synthesized, and the two cyclic
      subunits in 1 were found to recognize two different guest molecules (1,4
      dicyanobutane and paraquat) selectively or take up the two guest molecules
      simultaneously.

PMID- 25068153
TI  - Reduction of CO2 to free CO by a Pd(I)-Pd(I) dimer.
AB  - Reaction of CO2 with a Pd(I)-Pd(I) dimer supported by amido/bis(phosphine) pincer
      PNP ligands produces free CO in the presence of Me3SiCl and Me3SiOTf.

PMID- 25068154
TI  - Comparative STM studies of mixed ligand monolayers on gold nanoparticles in air
      and in 1-phenyloctane.
AB  - Scanning tunnelling microscopy (STM) studies have found stripe-like domains on
      gold nanoparticles (NPs) coated with certain binary mixtures of ligand molecules.
      The majority of these NPs' properties have been investigated for particles in
      solvents. Yet, most STM studies are for NPs in a dry state. Images of the same
      particles in air and liquid have not been obtained yet. In this work, a judicious
      choice of ligand molecules led to NPs with close-to-ideal STM imaging conditions
      in air and in 1-phenyloctane (PO). Large datasets under both conditions were
      acquired and rapidly evaluated through power spectral density (PSD) analysis. The
      result is a quantitative comparison of stripe-like domains in air and PO on the
      same NPs. PSD analysis determines a characteristic length-scale for these domains
      of ~1.0 nm in air and in PO showing persistence of striped domains in these two
      media. A length scale of ~0.7 nm for homoligand NPs was found.

PMID- 25068155
TI  - [Impact of aging on pathological personalities].

PMID- 25068156
TI  - A prize purpose.

PMID- 25068157
TI  - Parasite biology:    Piecing it together.

PMID- 25068158
TI  - Neither insects nor wind: ambophily in dioecious Chamaedorea palms (Arecaceae).
AB  - Pollination of Neotropical dioecious trees is commonly related to generalist
      insects. Similar data for non-tree species with separated genders are
      inconclusive. Recent studies on pollination of dioecious Chamaedorea palms
      (Arecaceae) suggest that species are either insect- or wind-pollinated. However,
      the wide variety of inflorescence and floral attributes within the genus suggests
      mixed pollination mode involving entomophily and anemophily. To evaluate this
      hypothesis, we studied the pollination of Chamaedorea costaricana, C.
      macrospadix, C. pinnatifrons and C. tepejilote in two montane forests in Costa
      Rica. A complementary morphological analysis of floral traits was carried out to
      distinguish species groups within the genus according to their most probable
      pollination mechanism. We conducted pollinator exclusion experiments, field
      observations on visitors to pistillate and staminate inflorescences, and trapped
      airborne pollen. A cluster analysis using 18 floral traits selected for their
      association with wind and insect pollination syndromes was carried out using 52
      Chamaedorea species. Exclusion experiments showed that both wind and insects,
      mostly thrips (Thysanoptera), pollinated the studied species. Thrips used
      staminate inflorescences as brood sites and pollinated pistillate flowers by
      deception. Insects caught on pistillate inflorescences transported pollen, while
      traps proved that pollen is wind-borne. Our empirical findings clearly suggest
      that pollination of dioecious Chamaedorea palms is likely to involve both insects
      and wind. A cluster analysis showed that the majority of studied species have a
      combination of floral traits that allow for both pollination modes. Our
      pollination experiments and morphological analysis both suggest that while some
      species may be completely entomophilous or anemophilous, ambophily might be a
      common condition within Chamaedorea. Our results propose a higher diversity of
      pollination mechanisms of Neotropical dioecious species than previously
      suggested.

PMID- 25068159
TI  - Does proximity to a mature forest contribute to the seed rain and recovery of an
      abandoned agriculture area in a semiarid climate?
AB  - Proximity to forests contributes to the recolonisation of anthropogenic-disturbed
      areas through seed input. We evaluated the role of proximity to a mature forest
      in the recolonisation of an agricultural area that has been abandoned for 18
      years and is currently a young forest. Seed rain was monitored at fixed distances
      from the mature forest. The type of surface recolonisation (germination versus
      resprouting) and the reproductive season were measured in both forests. The
      majority of plants recolonising the young forest originated from seed
      germination. Proximity to the mature forest contributed to the seed rain in the
      young forest; however, 18 years has not provided sufficient time for the
      recolonisation of 80 species present in the mature forest. Some species shared
      between forests differed in their fruiting season and seed dispersal. The seed
      rain had a total species richness of 56, a total density of 2270 seeds.m(
      2).year(-1) and predominance of self- and wind dispersal. A significant reduction
      in seed rain with increasing distance from the mature forest was observed. The
      young forest contained 35 species not observed in the mature forest, and the
      floristic similarity between the two forests was 0.5, indicating that the two
      forests are floristically distinct.

PMID- 25068160
TI  - Desiccation tolerance of Sphagnum revisited: a puzzle resolved.
AB  - As ecosystem engineers, Sphagnum mosses control their surroundings through water
      retention, acidification and peat accumulation. Because water retention avoids
      desiccation, sphagna are generally intolerant to drought; however, the literature
      on Sphagnum desiccation tolerance (DT) provides puzzling results, indicating the
      inducible nature of their DT. To test this, various Sphagnum species and other
      mesic bryophytes were hardened to drought by (i) slow drying; (ii) ABA
      application and (iii) chilling or frost. DT tolerance was assessed as recovery of
      chlorophyll fluorescence parameters after severe desiccation. We monitored the
      seasonal course of DT in bog bryophytes. Under laboratory conditions, following
      initial de-hardening, untreated Sphagnum shoots lacked DT; however, DT was
      induced by all hardening treatments except chilling, notably by slow drying, and
      in Sphagnum species of the section Cuspidata. In the field, sphagna in hollows
      and lawns developed DT several times during the growing season, responding to
      reduced precipitation and a lowered water table. Hummock and aquatic species
      developed DT only in late autumn, probably as a response to frost. Sphagnum
      protonemata failed to develop DT; hence, desiccation may limit Sphagnum
      establishment in drier habitats with suitable substrate chemistry. Desiccation
      avoiders among sphagna form compact hummocks or live submerged; thus, they do not
      develop DT in the field, lacking the initial desiccation experience, which is
      frequent in hollow and lawn habitats. We confirmed the morpho-physiological trade
      off: in contrast to typical hollow sphagna, hummock species invest more resources
      in water retention (desiccation avoidance), while they have a lower ability to
      develop physiological DT.

PMID- 25068161
TI  - Disease stage determines the efficacy of treatment of a  paediatric
      neurodegenerative disease.
AB  - Lysosomal storage disorders are a large group of inherited metabolic conditions
      resulting from the deficiency of proteins involved in lysosomal catabolism, with
      resulting accumulation of substrates inside the cell. Two-thirds of these
      disorders are associated with a neurodegenerative phenotype and, although few
      therapeutic options are available to patients at present, clinical trials of
      several treatments including lysosomal enzyme replacement are underway. Although
      animal studies indicate the efficacy of presymptomatic treatment, it is largely
      unknown whether symptomatic disease-related pathology and functional deficits are
      reversible. To begin to address this, we used a naturally-occurring mouse model
      with Sanfilippo syndrome (mucopolysaccharidosis type IIIA) to examine the
      effectiveness of intracisternal cerebrospinal fluid enzyme replacement in early,
      mid- and symptomatic disease stage mice. We observed a disease-stage-dependent
      treatment effect, with the most significant reductions in primary and secondary
      substrate accumulation, astrogliosis and protein aggregate accumulation seen in
      mucopolysaccharidosis type IIIA mice treated very early in the disease course.
      Affected mice treated at a symptomatic age exhibited little change in these
      neuropathological markers in the time-frame of the study. Microgliosis was
      refractory to treatment regardless of the age at which treatment was instigated.
      Although longer-term studies are warranted, these findings indicate the
      importance of early intervention in this condition.

PMID- 25068162
TI  - The use of action learning as a strategy for improving pain management  in the
      Emergency Department.

PMID- 25068163
TI  - Plasma soluble ST2 levels correlate with disease severity and predict clinical
      worsening in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Soluble suppression of tumorigenicity (sST2) has been proposed to be
      a marker for biomechanical strain and a possible predictor of mortality in
      patients with chronic heart failure. The use of sST2 in pulmonary arterial
      hypertension (PAH) has not been well defined. HYPOTHESIS: Plasma sST2 levels may
      correlate with the disease severity and predict clinical worsening in PAH.
      METHODS: We performed a cohort study of 40 idiopathic PAH patients with data on
      demographics, exercise capacity, echocardiographic parameters, laboratory tests,
      hemodynamics, and medications. Plasma sST2 was assessed with the high-sensitivity
      ST2 ELISA kit at diagnostic catheterization. All patients were followed up from
      the date of blood sampling. The endpoint was clinical worsening. RESULTS: sST2
      was significantly elevated in patients with idiopathic PAH compared with control
      subjects (28.9 +/- 13.9 vs 20.7 +/- 7.5 ng/mL, P = 0.003). Pearson correlation
      analysis revealed that sST2 levels correlated with cardiac index (r = -0.534, P =
      0.000) and pulmonary vascular resistance (r = 0.350, P = 0.027), and could
      reflect disease severity of PAH. After a mean follow-up of 14 +/- 5 months, 12
      patients showed clinical worsening. Receiver operating characteristic analysis
      suggested that sST2 levels >31.4 ng/mL discriminated clinical worsening with a
      sensitivity and specificity of 83.3% and 78.6%, respectively. Kaplan-Meier
      analysis showed that higher sST2 levels (>31.4 ng/mL) were associated with poor
      clinical outcomes (P = 0.008). Multivariate Cox regression analysis showed that
      sST2 was an independent predictor of clinical worsening (hazard ratio: 6.067, 95%
      confidence interval: 1.317-27.948, P = 0.021). CONCLUSIONS: sST2 correlates with
      disease severity and is a significant predictor of clinical worsening in patients
      with PAH.

PMID- 25068164
TI  - Edouard Kieffer: a master in vascular surgery.

PMID- 25068165
TI  - Perception vs. reality: an investigation of the misperceptions concerning the
      extent of peer novel drug use.
AB  - Misperceptions of peer substance use have previously been implicated as
      significant influences on individual use of both alcohol and illicit drugs.
      However, research on perceived social norms and related interventions are
      typically limited to binge drinking and marijuana and no empirical studies have
      explored misperceptions related to "novel drugs." The present study explored the
      extent of use and perceptions of use among a college sample (N = 2,349) for three
      categories of novel drugs: synthetic cannabinoids (Spice, K2, Mr. Miyagi, Pot
      Pourri, etc.), synthetic cathinones (commonly known as "bath salts"), and Salvia
      divinorum. Results indicate that overall perceived use was significantly higher
      than actual reported use. The frequency of overestimation of peer use was
      particularly large for the emerging drugs when compared to alcohol and marijuana.
      This finding is concerning as these misperceptions have the potential to
      influence students toward experimentation with these substances and suggests that
      a possible target for intervention is misperceptions of emerging novel
      substances.

PMID- 25068166
TI  - Experiences of Australian school staff in addressing student cannabis use.
AB  - Cannabis is the most frequently used illicit drug by Australian secondary school
      students yet there is scant research investigating school staff responses to
      student cannabis use. As such, this study surveyed 1,692 school staff who
      attended Generation Next seminars throughout Australia. The self-complete survey
      identified that the majority of school staff had discussed cannabis use at least
      once in the past year, although teachers were less likely to report having
      cannabis-related discussions compared to other school staff. Staff drug education
      training was consistently associated with an increased prevalence of cannabis
      related discussion and assistance. These findings highlight a need for drug
      education among school staff and particularly among teachers.

PMID- 25068167
TI  - Assess the impact of an online tobacco prevention training program on teachers
      and their students.
AB  - School-based tobacco prevention programs have been proven effective in reducing
      tobacco use. This evaluation aimed to assess the impact of an online tobacco
      prevention teacher training program on teachers and their students in Florida
      schools. A total of 344 teachers, including 72 K-3 grade teachers, 44 4th-5th
      grade teachers, and 228 6th-12th grade teachers completed the online training
      program and 323 (93.9%) were followed up to assess impacts on their 6,490
      students. Results suggested that the online tobacco prevention education program
      for teachers was effective with high satisfaction and the impact on students was
      significant in improving knowledge and attitude about tobacco use and in
      increasing the proportion of 6-12th grade students who decided not to use
      tobacco. The evaluation study recommended the online education program be
      continued and expanded in the future.

PMID- 25068168
TI  - Cross-national study on factors that influence parents' knowledge about their
      children's alcohol use.
AB  - Previous research has shown that parents underestimate their children's substance
      use. The aim of the present work was to analyze parental estimation of their
      children's use of alcohol in five countries from northern, central, and southern
      Europe, and to explore the variables that influenced this perceptual bias. The
      sample comprised 1181 parent-children dyads living in Sweden, Slovenia, the Czech
      Republic, Spain, and Portugal. In accordance with the findings of previous
      studies, we found high parental underestimation of substance use, which was
      greater for more frequent alcohol use or the use of illegal drugs. This
      underestimation appears to be subject to some degree of sociocultural influence,
      and is also influenced by the severity of the children's use.

PMID- 25068169
TI  - Faculty perceptions of their roles in alcohol education/prevention.
AB  - Alcohol use among college students continues to be a major public health threat
      to our nation. The purpose of this study was to explore faculty perceptions of
      their roles and responsibilities in alcohol education and prevention. The
      researchers adapted the Core Faculty and Staff Environmental Alcohol and Other
      Drug Survey to include only questions regarding alcohol and created additional
      questions concerning Friday classes. The survey was sent to all faculty members
      (N = 1,712). Completed surveys were collected from 122 faculty members (7.1%).
      The majority (95%) agreed that institutions of higher education should be
      involved in alcohol awareness efforts. Fewer (76%) agreed that they could
      positively affect students' alcohol consumption. Responses from open-ended
      questions revealed areas where faculty perceived they could have the most impact.
      Recommendations include implementing the Institute of Medicine strategies on
      campuses and incorporating faculty in these alcohol education and prevention
      strategies.

PMID- 25068170
TI  - Drugged driving: increased traffic risks involving licit and illicit substances.
AB  - Driving under the influence of drugs poses risks for traffic safety. Most
      research attention has been focused on the most prevalent drugs of abuse, such as
      alcohol, illegal drugs, and prescription drugs with high abuse potential. The
      objectives of this study were to determine the types of drugs used by convicted
      DUI offenders on the day of their arrest, prevalence of poly-substance use, and
      offender characteristics associated with different drug use patterns. Data were
      collected from 6,339 individuals enrolled in the court-mandated Mississippi
      Alcohol Safety Education Program. After alcohol, cannabis was the most frequently
      used substance, followed by sedative medications and prescription analgesics.
      Among poly-substance users, 78.4% reported combining alcohol with other drugs.
      Findings could be used to inform public education campaigns, law enforcement
      training, and highway safety policies about the prevalence of combining alcohol
      with other drugs, as well as how poly-substance use further impairs traffic
      related risks.

PMID- 25068171
TI  - Vision and licensure, key to success in HOPE's model.

PMID- 25068172
TI  - Glucocorticoid regimens for prevention of Graves' ophthalmopathy progression
      following radioiodine treatment: systematic review and meta-analysis.
AB  - BACKGROUND: Glucocorticoid (GC) therapy has been shown to prevent Graves'
      ophthalmopathy (GO) progression following radioactive iodine (RAI) treatment.
      However, the optimal regimen is controversial, with studies from recent years
      suggesting the use of lower doses and shorter GC treatment courses. METHODS: We
      conducted a systematic review and meta-analysis of randomized controlled trials
      (RCTs) and retrospective controlled trials comparing GC regimens versus placebo,
      no treatment, or other GC regimens. RESULTS: Eight trials evaluating 850 patients
      fulfilled inclusion criteria. In patients with preexisting GO, standard dose
      prednisone (0.4-0.5 mg/kg tapered over 3 months) was very effective for
      prevention of GO progression (OR 0.14 [CI 0.06-0.35], p<0.01) in patients with
      mild to moderate GO. Two studies evaluated low-dose prednisone (0.2-0.3 mg/kg for
      4-6 weeks) in patients with mild GO or risk factors, but were limited by not
      including patients with preexisting GO in the control groups. Therefore, the two
      low-dose groups were evaluated using indirect comparisons with control groups
      matched for age and clinical activity score, showing excellent efficacy versus no
      treatment or placebo (OR 0.20 [CI 0.07-0.60], p=0.004) and no significant
      difference compared with standard dose (OR 1.7 [CI 0.52-5.52], p=0.47). In
      patients without preexisting GO, steroid prophylaxis had no beneficial effect (OR
      1.87 [CI 0.81-4.3]), though there were insufficient data regarding patients with
      risk factors for GO development. GC prophylaxis had no impact on hyperthyroidism
      resolution (OR 1.05 [CI 0.69-1.58]), and GC side effects were common but mild.
      CONCLUSIONS: Current evidence supports a three-tier approach for prevention of GO
      progression following RAI. Standard dose prednisone is the best validated regimen
      and should be used in patients with mild to moderate GO who have high risk of
      progression, while low dose prednisone can be used in patients with mild GO, and
      in patients without preexisting GO who have risk factors and are selected for GC
      prophylaxis. Patients without preexisting GO and without risk factors should not
      be treated with GC prophylaxis.

PMID- 25068173
TI  - New basic insights into the low hot electron injection efficiency of gold
      nanoparticle-photosensitized titanium dioxide.
AB  - The low hot electrons injection efficiency (HEIE) from plasmonic metal to
      semiconductor significantly affects the performance of metal-semiconductor
      composite. However, there are few reports about the origin of this low HEIE. In
      the present work, the factors affecting the transfer process and generation
      efficiency of hot electron in Au@TiO2 composite are investigated using first
      principles calculations and Maxwell's electrodynamics theory. The occupation of
      surface oxygen vacancies of TiO2 by gold atoms is found to increase the hot
      electrons transfer barrier and expand the space charge region, which decrease the
      HEIE. In addition, the existing Au@TiO2 structure going against the generation of
      large amount of hot electrons may also lead to low HEIE. Our results reveal that
      the replacement of divalent host oxygen atoms with monovalent atoms can decrease
      the HEIE and comparison with experimental results allows us to validate our
      predictions. Furthermore, proper surface treatment of semiconductor before
      depositing metal particles and structure optimization of the composite are
      suggested to improve the HEIE. 

PMID- 25068174
TI  - Ni-catalyzed carboxylation of unactivated primary alkyl bromides and sulfonates
      with CO2.
AB  - A Ni-catalyzed carboxylation of unactivated primary alkyl bromides and sulfonates
      with CO2 at atmospheric pressure is described. The method is characterized by its
      mild conditions and remarkably wide scope without the need for air- or moisture
      sensitive reagents, which make it a user-friendly and operationally simple
      protocol en route to carboxylic acids. 

PMID- 25068175
TI  - Molecular dynamics simulation of water/BHDC cationic reverse micelles. structural
      characterization, dynamical properties, and influence of solvent on intermicellar
      interactions.
AB  - We report results obtained from molecular dynamics (MD) experiments of
      benzylhexadecyldimethylammonium chloride (BHDC) cationic reverse micelles (RMs).
      In particular we analyzed equilibrium and dynamical characteristics of water/BHDC
      RMs in pure benzene, at two different water/BHDC ratios (W0 = 5 and W0 = 10). The
      RMs appear as elliptical aggregates with eccentricities close to ~0.9. Analysis
      of the different spatial correlations reveals three different spatial domains in
      the RMs: a water inner pool, the surfactant interface, and the external solvent.
      The calculated accessible surface areas for the aqueous inner cores suggest a
      strong penetration of solvent molecules within the micellar interface domains.
      Comparison between the density profiles of both RMs shows an increment of the
      broadness in the distributions of all species at the interface, along with an
      increasing overlap between the tail segments of the surfactant and benzene
      molecules as one considers larger micelles. For the dynamical side, the
      rotational characteristic time scale for the confined water was found to be 1
      order of magnitude larger than that of the bulk water. A similar effect was also
      observed for hydrogen bond dynamics. Both retardation effects diminish with the
      size of the aggregate. To the estimate the influence of the external solvent on
      the intermicellar interactions, free energy profiles for the coalescence process
      between RMs of similar size in pure benzene and in a n-heptane/benzene mixture
      were also investigated. The results indicate that the association process is
      facilitated by the presence of n-heptane in the external nonpolar phase.
      Comparison with previous theoretical and experimental results is also carried
      out. 

PMID- 25068176
TI  - Effects of electron trapping and protonation on the efficiency of water-splitting
      dye-sensitized solar cells.
AB  - Water-splitting dye-sensitized photoelectrochemical (WS-DSPECs) cells employ
      molecular sensitizers to absorb light and transport holes across the TiO2 surface
      to colloidal or molecular water oxidation catalysts. As hole diffusion occurs
      along the surface, electrons are transported through the mesoporous TiO2 film. In
      this paper we report the effects of electron trapping and protonation in the TiO2
      film on the dynamics of electron and hole transport in WS-DSPECs. When the
      sensitizer bis(2,2'-bipyridine)(4,4'-diphosphonato-2,2'-bipyridine)ruthenium(II)
      is adsorbed from aqueous acid instead of from ethanol, there is more rapid hole
      transfer between photo-oxidized sensitizer molecules that are adsorbed from
      strong acid. However, the photocurrent and open-circuit photovoltage are
      dramatically lower with sensitizers adsorbed from acid because intercalated
      protons charge-compensate electron traps in the TiO2 film. Kinetic modeling of
      the photocurrent shows that electron trapping is responsible for the rapid
      electrode polarization that is observed in all WS-DSPECs. Electrochemical
      impedance spectroscopy suggests that proton intercalation also plays an important
      role in the slow degradation of WS-DSPECs, which generate protons at the anode as
      water is oxidized to oxygen. 

PMID- 25068177
TI  - Lessons learned while preparing a tailored, self-help, technology-driven
      intervention for national dissemination.
AB  - Tailored health interventions have been found to be effective in various areas of
      health promotion because of their delivery of customized content, which focuses
      the prevention messages more closely on the individual's risk behavior. However,
      the use of tailored interventions in the prevention of STD/HIV has been limited,
      and there is a void in the literature on translating tailored interventions into
      practice. This paper discusses the process of translating a tailored, self-help,
      technology-driven STD/HIV prevention intervention from research-to-practice.
      Three agencies were selected during the translation process to test the
      intervention materials and provided valuable lessons learned for translating a
      tailored intervention into practice. A racially diverse group of more than 250
      women in six states participated in the intervention during this pilot test.
      Lessons learned for research-to-practice efforts for tailored interventions are
      presented, including expanding the reach of such interventions by making them
      more compatible for mobile technology. 

PMID- 25068178
TI  - Efficacy of theory-based HIV behavioral prevention among rural-to-urban migrants
      in China: a randomized controlled trial.
AB  - Our objective was to evaluate the efficacy of a cultural adaptation of a social
      cognitive theory-based HIV behavioral prevention program among young rural-to
      urban migrants in China. The intervention design and assessment were guided by
      the Protection Motivation Theory (PMT). The intervention was evaluated through a
      randomized controlled trial with 6-month and 12-month follow-ups. The primary
      behavioral outcome was the use of condoms. Other outcome measures include HIV
      knowledge, condom use knowledge, HIV-related perceptions (PMT constructs), and
      intention to use condom. The mixed-effects regression models for condom use with
      regular partners indicated that overall frequency of condom use, condom use in
      last three sexual acts and proper condom use increased over time for the
      participants but the increases were significantly greater among the intervention
      group than the control group at 6-month and 12-month follow-ups. The mixed
      effects models for HIV-related perceptions indicated that extrinsic rewards,
      intrinsic rewards, and response costs decreased while vulnerability, severity,
      response efficacy, and self-efficacy increased over time for the intervention
      group. The increases in HIV knowledge, condom use knowledge, and intention to use
      condom were also significantly greater among the intervention group than the
      control group. The data in the current study suggested efficacy of a social
      cognitive theory-based behavioral intervention in increasing condom use among
      young migrants in China. The intervention also increased protective perceptions
      and decreased risk perception posited by the theory (i.e., PMT). 

PMID- 25068179
TI  - "Know Your Status": results from a novel, student-run HIV testing initiative on
      college campuses.
AB  - Know Your Status (KYS), a novel, student-run program offered free HIV-testing at
      a private university (PU) and community college (CC). Following completion of
      surveys of risk behaviors/reasons for seeking testing, students were provided
      with rapid, oral HIV-testing. We investigated testing history, risk behaviors,
      and HIV prevalence among students tested during the first three years of KYS. In
      total, 1408 tests were conducted, 5 were positive: 4/408 CC, 1/1000 PU (1% vs.
      0.1%, p=0.01). Three positives were new diagnoses, all black men-who-have-sex
      with-men (MSM). Over 50% of students were tested for the first time and 59%
      reported risk behaviors. CC students were less likely to have used condoms at
      last sex (a surrogate for risk behavior) compared to PU (OR 0.73, CI [0.54,
      0.98]). Race, sexual identity, and sex were not associated with condom use. These
      results demonstrate that KYS successfully recruited large numbers of previously
      untested, at-risk students, highlighting the feasibility and importance of
      testing college populations.

PMID- 25068180
TI  - HIV testing among MSM in Bogota, Colombia: the role of structural and individual
      characteristics.
AB  - This study used mixed methods to examine characteristics related to HIV testing
      among men who have sex with men (MSM) in Bogota, Colombia. A sample of 890 MSM
      responded to a computerized quantitative survey. Follow-up qualitative data
      included 20 in-depth interviews with MSM and 12 key informant interviews.
      Hierarchical logistic set regression indicated that sequential sets of variables
      reflecting demographic characteristics, insurance coverage, risk appraisal, and
      social context each added to the explanation of HIV testing. Follow-up logistic
      regression showed that individuals who were older, had higher income, paid for
      their own insurance, had had a sexually transmitted infection, knew more people
      living with HIV, and had greater social support were more likely to have been
      tested for HIV at least once. Qualitative findings provided details of personal
      and structural barriers to testing, as well as inter-relationships among these
      factors. Recommendations to increase HIV testing among Colombian MSM are offered.

PMID- 25068181
TI  - Novel approaches to HIV prevention and sexual health promotion among Guatemalan
      gay and bisexual men, MSM, and transgender persons.
AB  - The burden of HIV is disproportionate for Guatemalan sexual minorities (e.g., gay
      and bisexual men, men who have sex with men [MSM], and transgender persons). Our
      bi-national partnership used authentic approaches to community-based
      participatory research (CBPR) to identify characteristics of potentially
      successful programs to prevent HIV and promote sexual health among Guatemalan
      sexual minorities. Our partnership conducted Spanish-language focus groups with
      87 participants who self-identified as male (n=64) or transgender (n=23) and
      individual in-depth interviews with ten formal and informal gay community
      leaders. Using constant comparison, an approach to grounded theory, we identified
      20 characteristics of potentially successful programs to reduce HIV risk,
      including providing guidance on accessing limited resources; offering supportive
      dialogue around issues of masculinity, socio-cultural expectations, love, and
      intimacy; using Mayan values and images; harnessing technology; increasing
      leadership and advocacy skills; and mobilizing social networks. More research is
      clearly needed, but participants reported needing and wanting programming and had
      innovative ideas to prevent HIV exposure and transmission.

PMID- 25068183
TI  - Bioinspired magneto-optical bacteria.
AB  - "Two-in-one" magneto-optical bacteria have been produced using the probiotic
      Lactobacillus fermentum for the first time. We took advantage of two features of
      bacteria to synthesize this novel and bifunctional nanostructure: their metal
      reducing properties, to produce gold nanoparticles, and their capacity to
      incorporate iron oxide nanoparticles at their external surface. The magneto
      optical bacteria survive the process and behave as a magnet at room temperature. 

PMID- 25068182
TI  - Comparing three cohorts of MSM sampled via sex parties, bars/clubs, and
      Craigslist.org: implications for researchers and providers.
AB  - With limited exceptions, few studies have systematically reported on psychosocial
      and demographic characteristic differences in samples of men who have sex with
      men (MSM) based on where they were recruited. This study compared three sexually
      active cohorts of MSM recruited via Craigslist.org (recruited via modified time
      space sampling), gay bars and clubs (recruited via time-space sampling), and
      private sex parties (identified via passive recruitment and listserves), finding
      mixed results with regard to differences in demographic characteristics, STI
      history, and psychosocial measures. Men recruited from sex parties were
      significantly older, reported more symptoms of sexual compulsivity, more likely
      to be HIV-positive, more likely to report a history of STIs, and more likely to
      self-identify as a barebacker, than men recruited from the other two venues. In
      contrast, men from Craigslist.org reported the lowest levels of attachment to the
      gay and bisexual community and were the least likely to self-identify as gay. Men
      from bars and clubs were significantly younger, and were more likely to report
      use of hallucinogens and crack or cocaine. Our findings highlight that the venues
      in which MSM are recruited have meaningful consequences in terms of the types of
      individuals who are reached. 

PMID- 25068184
TI  - Biomimetic production of silk-like recombinant squid sucker ring teeth proteins.
AB  - The sucker ring teeth (SRT) of Humboldt squid exhibit mechanical properties that
      rival those of robust engineered synthetic polymers. Remarkably, these properties
      are achieved without a mineral phase or covalent cross-links. Instead, SRT are
      exclusively made of silk-like proteins called "suckerins", which assemble into
      nanoconfined beta-sheet reinforced supramolecular networks. In this study, three
      streamlined strategies for full-length recombinant suckerin protein production
      and purification were developed. Recombinant suckerin exhibited high solubility
      and colloidal stability in aqueous-based solvents. In addition, the colloidal
      suspensions exhibited a concentration-dependent conformational switch, from
      random coil to beta-sheet enriched structures. Our results demonstrate that
      recombinant suckerin can be produced in a facile manner in E. coli and processed
      from mild aqueous solutions into materials enriched in beta-sheets. We suggest
      that recombinant suckerin-based materials offer potential for a range of
      biomedical and engineering applications. 

PMID- 25068186
TI  - In vitro activity of tigecycline in combination with cefoperazone-sulbactam
      against multidrug-resistant Acinetobacter baumannii.
AB  - Over the last decade, multidrug-resistant Acinetobacter baumannii (MDRAB) has
      emerged as one of the most problematic nosocomial pathogens. Empirical
      combination therapy has become a common practice to treat patients infected with
      MDRAB. In vitro interactions of tigecycline with cefoperazone-sulbactam were
      assessed in 72 MDRAB isolates. Minimum inhibitory concentrations (MICs) were
      determined by broth microdilution method. Antibiotic interactions were determined
      by chequerboard and time-kill assays. Chequerboard analysis showed 29.2% synergy
      and no antagonistic interactions. Time-kill assays confirmed the synergistic
      interaction between two agents for three of four selected extensively drug
      resistant A. baumannii (XDRAB) isolates. No antagonism was revealed by time-kill
      assays. Moreover, tigecycline in combination with cefoperazone-sulbactam appeared
      to be more effective than tigecycline in combination with sulbactam against
      XDRAB. In conclusion, in vitro synergistic activities of tigecycline in
      combination with cefoperazone-sulbactam against MDRAB were demonstrated,
      suggesting a superior treatment option against MDRAB. 

PMID- 25068185
TI  - All-trans retinoic acid and arsenic trioxide induce apoptosis and modulate
      intracellular concentrations of calcium in hepatocellular carcinoma cells.
AB  - We investigated the effects of all-trans retinoic acid (ATRA) and arsenic
      trioxide (ATO), alone and in combination, on apoptosis and intracellular calcium
      concentration in hepatocellular carcinoma (HepG2) cells. We used HepG2 cells to
      test the effects of ATRA and ATO, individually and in combination, on cell
      proliferation, apoptosis, and intracellular-free calcium concentration. The
      results indicate that each drug decreased cell proliferation, increased
      apoptosis, and increased intracellular-free calcium in a time- and dose-dependent
      manner. We also calculated the coefficients of drug interaction for sub-threshold
      administration of both drugs in combination (1 MUmol/L each). ATRA and ATO acted
      synergistically in inhibition of cell proliferation and additively in the
      promotion of apoptosis. All-trans retinoic acid and ATO interacted
      synergistically to reduce cell proliferation in HepG2 cells. 

PMID- 25068187
TI  - A method detection limit for the analysis of natural organic matter via Fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - Fourier Transform Ion Cyclotron Resonance mass spectra (FT-ICR-MS) of natural
      organic matter are complex and consist of several thousands of peaks. The
      corresponding mass to charge ratios (m/z) and signal intensities result from
      analytes and noise. The most commonly applied way of distinguishing between
      analyte and noise is a fixed signal-to-noise ratio below which a detected peak is
      considered noise. However, this procedure is problematic and can yield ambiguous
      results. For example, random noise peaks can occur slightly above the signal-to
      noise threshold (false positives), while peaks of low abundance analytes may
      occasionally fall below the fixed threshold (false negatives). Thus, cumulative
      results from repeated measurements of the same sample contain more peaks than a
      single measurement. False positive and false negative signals are difficult to
      distinguish, which affects the reproducibility between replicates of a sample. To
      target this issue, we tested the feasibility of a method detection limit (MDL)
      for the analysis of natural organic matter to identify peaks that can reliably be
      distinguished from noise by estimating the uncertainty of the noise. We performed
      556 replicate analyses of a dissolved organic matter sample from the deep North
      Pacific on a 15 T FT-ICR-MS; each of these replicate runs consisted of 500
      cumulated broadband scans. To unambiguously identify analyte peaks in the mass
      spectra, the sample was also run at time-consuming high-sensitivity settings. The
      resulting data set was used to establish and thoroughly test a MDL. The new
      method is easy to establish with software help, does only require the additional
      analysis of replicate blanks (low time increase), and can implement all steps of
      sample preparation. Especially when analysis time does not allow for replicate
      runs, major merits of the MDL are reliable removal of false positive (noise)
      peaks and better reproducibility, while the risk of losing analytes with low
      signal intensities (false negative) is comparatively low. When replicate analyses
      are feasible, the removal of all singly detected peaks is further recommended, as
      these have the highest probability of being noise peaks. We suggest that the here
      proposed detection limit should become routine in FT-ICR-MS data processing. 

PMID- 25068189
TI  - Five-Year Follow-Up of a 30-Month Trial of Stability of Silicone Band Frontalis
      Suspension for the Treatment of Severe Unilateral Upper Eyelid Ptosis in Infants.
AB  - PURPOSE: To evaluate the five-year stability of frontalis suspension of the upper
      eyelid with a silicone band for the treatment of severe congenital ptosis in
      infants. METHODS: Chart review of pediatric patients with a follow-up of five
      years after unilateral frontalis suspension with silicone band was reviewed.
      Margin-reflex distance (MRD) and corneal staining were measured at different
      follow-up visits. Data were analyzed by analysis of variance and t test for
      paired data. RESULTS: Twenty pediatric patients were included in this
      retrospective study. MRD was severely reduced before surgery in all cases: it
      ranged from -1 mm to -4 mm (-2.4 +/- 0.8 mm). After surgery, MRD increased to 2.9
      +/- 0.3 mm, and then progressively decreased by 0.6 mm within the first three
      months (p < 0.001); a further reduction of 0.2 mm, occurring between three and 12
      months after surgery, was not statistically significant (p < 0.001). Between the
      12-month and the five-year follow-up visits (one visit every six months), no
      changes in MRD were found for any patient. After the five-years visit, no
      substantial changes were recorded in 18 patients (90%); in two patients, a second
      surgery to improve the deterioration was necessary. Corneal staining, which was
      present in five patients (25%) during the first two postoperative weeks,
      disappeared over five years of follow-up. CONCLUSIONS: During the five-year
      follow-up of this retrospective study, the frontalis suspension with a silicone
      band proved to be a stable procedure. After 30 months from the first observation,
      MRD values were stable, except for two patients that underwent a second surgery
      to stabilize the worsening ptosis.

PMID- 25068188
TI  - Consistency and Accuracy of Multiple Pain Scales Measured in Cancer Patients From
      Multiple Ethnic Groups.
AB  - BACKGROUND: Standardized pain-intensity measurement across different tools would
      enable practitioners to have confidence in clinical decision making for pain
      management. OBJECTIVES: The purpose was to examine the degree of agreement among
      unidimensional pain scales and to determine the accuracy of the multidimensional
      pain scales in the diagnosis of severe pain. METHODS: A secondary analysis was
      performed. The sample included a convenience sample of 480 cancer patients
      recruited from both the Internet and community settings. Cancer pain was measured
      using the Verbal Descriptor Scale (VDS), the visual analog scale (VAS), the Faces
      Pain Scale (FPS), the McGill Pain Questionnaire-Short Form (MPQ-SF), and the
      Brief Pain Inventory-Short Form (BPI-SF). Data were analyzed using a multivariate
      analysis of variance and a receiver operating characteristic curve. RESULTS: The
      agreement between the VDS and VAS was 77.25%, whereas the agreement was 71.88%
      and 71.60% between the VDS and FPS, and VAS and FPS, respectively. The MPQ-SF and
      BPI-SF yielded high accuracy in the diagnosis of severe pain. Cutoff points for
      severe pain were more than 8 for the MPQ-SF and more than 14 for the BPI-SF,
      which exhibited high sensitivity and relatively low specificity. CONCLUSION: The
      study found substantial agreement between the unidimensional pain scales and high
      accuracy of the MPQ-SF and the BPI-SF in the diagnosis of severe pain.
      IMPLICATIONS FOR PRACTICE: Use of 1 or more pain screening tools that have
      validated diagnostic accuracy and consistency will help classify pain effectively
      and subsequently promote optimal pain control in multiethnic groups of cancer
      patients.

PMID- 25068190
TI  - Toward a common identity for relationally oriented clinicians: a place to hang
      one's hat.
AB  - The goal of this special section is to work toward establishing a common identity
      for relationally inclined clinicians across proscribed theoretical orientations,
      facilitating a shared identity among diverse psychotherapists while placing a
      spotlight on relationship research. This article discusses the need for a more
      coherent and less polarizing professional identity for psychotherapists and why a
      more universal relational orientation to psychotherapy is timely given the
      current state of psychotherapy practice and research. Lastly, common relational
      themes that run throughout the diverse treatment paradigms presented in this
      special section are discussed, framing what it means to be a relational
      psychotherapist while hopefully providing some direction for future research and
      clinical training.

PMID- 25068191
TI  - An integrative relational point of view.
AB  - This article, part of a special section on the Relational Foundations of
      Psychotherapy, describes a particular relational approach called cyclical
      psychodynamics. Cyclical psychodynamics is rooted both in the relational
      perspective in psychoanalysis and in an integrative melding of psychodynamic,
      cognitive-behavioral, systemic, and experiential points of view. Central to its
      theoretical structure is a focus on the vicious and virtuous circles that
      perpetuate (or contribute to changing) personality patterns that may have
      originated in childhood but that persist because they often generate the very
      feedback from others that is necessary to keep them going. As a consequence of
      this latter focus, the relational foundation of cyclical psychodynamic therapy
      addresses in equal and dynamically reciprocal fashion both the therapeutic
      relationship in the consulting room and the key relationships outside the
      consulting room that play an essential role in the maintenance or change of the
      problematic patterns the person has come to therapy to work on.

PMID- 25068192
TI  - The therapeutic relationship in emotion-focused therapy.
AB  - Important qualities of the relationship that make it therapeutic are discussed.
      The relationship is seen as both therapeutic in and of itself and as providing a
      facilitative environment from specific change processes. The role of the
      relationship in emotion-focused therapy is discussed within this framework. The
      relationship in emotion-focused therapy is seen as curative by serving an affect
      regulation function, which is internalized over time by the client. This function
      is accomplished by offering a soothing affect-attuned bond characterized by the
      therapist's presence and empathic attunement to affect as well as acceptance and
      congruence. Second, the relationship is seen as functioning as a means to an end
      by offering an optimal environment for facilitating specific modes of emotional
      processing. In our view, affect is much more likely to be approached, tolerated,
      and accepted in the context of a safe relationship.

PMID- 25068193
TI  - The relationship in motivational interviewing.
AB  - The therapeutic relationship in motivational interviewing is hypothesized to have
      both a direct impact on client outcomes as well as facilitating the emergence of
      client language in favor of change. The nature of this relationship is
      characterized by empathy, partnership, and support of the client's autonomy
      commonly called the spirit of the method. This article explores the implications
      of this spirit on the practice and understanding of motivational interviewing,
      including common misconceptions attributable to a misunderstanding of the role of
      the relationship.

PMID- 25068194
TI  - The right brain is dominant in psychotherapy.
AB  - This article discusses how recent studies of the right brain, which is dominant
      for the implicit, nonverbal, intuitive, holistic processing of emotional
      information and social interactions, can elucidate the neurobiological mechanisms
      that underlie the relational foundations of psychotherapy. Utilizing the
      interpersonal neurobiological perspective of regulation theory, I describe the
      fundamental role of the early developing right brain in relational processes,
      throughout the life span. I present interdisciplinary evidence documenting right
      brain functions in early attachment processes, in emotional communications within
      the therapeutic alliance, in mutual therapeutic enactments, and in therapeutic
      change processes. This work highlights the fact that the current emphasis on
      relational processes is shared by, cross-fertilizing, and indeed transforming
      both psychology and neuroscience, with important consequences for clinical
      psychological models of psychotherapeutic change.

PMID- 25068195
TI  - Relationship science and practice in psychotherapy: closing commentary.
AB  - In this special section, authors discussed the therapeutic relationship in their
      respective theoretical orientations. The invited authors defined their relational
      approaches and identified the most important facets (e.g., alliance, empathy,
      immediacy) in their particular approaches. In this closing commentary, we remark
      on the constituent articles, offer a research summary of the contribution of
      relational behaviors to treatment outcome, and highlight the flourishing
      convergence of relationship science and practice in psychotherapy.

PMID- 25068198
TI  - Photocatalytic decarboxylative reduction of carboxylic acids and its application
      in asymmetric synthesis.
AB  - The decarboxylative reduction of naturally abundant carboxylic acids such as
      alpha-amino acids and alpha-hydroxy acids has been achieved via visible-light
      photoredox catalysis. By using an organocatalytic photoredox system, this method
      offers a mild and rapid entry to a variety of high-value compounds including
      medicinally relevant scaffolds. Regioselective decarboxylation is achieved when
      differently substituted dicarboxylic acids are employed. The application of this
      method to the synthesis of enantioenriched 1-aryl-2,2,2-trifluoroethyl chiral
      amines starting from natural alpha-amino acids further testifies to the utility
      of the developed photocatalytic decarboxylative reduction protocol. 

PMID- 25068199
TI  - Underage youth trading sex in the Philippines: trafficking and HIV risk.
AB  - This study examines the socio-structural sexual health risks of female youth
      (aged 14-17) working in bar/spa venues and brothels in the Philippines, compared
      to their older counterparts. Aside from this study, few female sex work studies
      have interviewed youth under 18. On four southern Philippines islands, 770 female
      sex workers (FSWs), aged 14-48, were recruited from bar/spa venues and brothels
      to participate in a socio-structural HIV prevention study. Controlling for the
      effects of a larger HIV prevention intervention study involving 1484 female
      bar/spa workers, the minors, compared to older FSWs, had less education (AOR:
      0.81, CI: 0.70-0.94), less children (AOR: 0.19, CI: 0.10-0.37), and were more
      likely to work in illegal brothels (AOR: 4.60, CI: 1.66-12.75) and to be high on
      drugs during sex (AOR: 2.26, CI: 1.39-3.67). It was less likely that anyone
      talked to them about HIV prevention (AOR: 0.32, CI: 0.15-0.72), but more likely
      they were recruited by venue owners (AOR: 5.67, 1.56-20.56) and were told by
      their managers to have sex without a condom (AOR: 6.80, CI: 2.06-22.39). Results
      suggest a need for organizational and policy level interventions to protect
      adolescent females from working in unsafe environments in the Philippines and to
      prevent youth from being recruited into high-risk situations.

PMID- 25068200
TI  - Anti-inflammatory lignanamides from the roots of Solanum melongena L.
AB  - Four new lignanamides, melongenamides A-D (1-4), together with six known ones (5
      10), were isolated from the roots of Solanum melongena L. Their structures were
      elucidated on the basis of 1D and 2D NMR experiments and by comparison of their
      spectroscopic and physical data with the literature values. Compounds 2-8
      exhibited inhibitions of nitric oxide production in lipopolysaccharide-induced
      RAW 264.7 macrophages with IC50 values ranging from 16.2 to 58.5 MUM.

PMID- 25068201
TI  - Monoterpene derivatives from the roots of Paeonia lactiflora and their anti
      proliferative activity.
AB  - An unusual nor-monoterpene with only nine carbons, nor-paeonilactone (1), two new
      monoterpenes, paeonisuffrone C (2), paeonilactone D (9), and a new monoterpene
      glucoside, paeonin D (3), along with ten known compounds were isolated from the
      dried roots of Paeonia lactiflora. Their structures were elucidated on the basis
      of spectroscopic analysis, including 1D and 2D NMR, and computational data.
      Compounds 4-14 were evaluated for their anti-proliferative activities against BT
      483 human breast cancer cells and OVCA 429 human ovarian cancer cells by MTT
      assay. 

PMID- 25068202
TI  - 2-(2-phenylethyl)chromone derivatives from Chinese agarwood induced by artificial
      holing.
AB  - Three new 2-(2-phenylethyl)chromone derivatives (1-3), together with thirteen
      known ones (4-16), were isolated from the EtOAc extract of Chinese agarwood
      induced by artificial holing, originating from Aquilaria sinensis (Lour.) Gilg
      (Thymelaeaceae). The chemical structures of the new compounds were identified by
      spectroscopic techniques (UV, IR, MS, 1D and 2D NMR). Compounds 1, 6, 15 and 16
      exhibited inhibitory effects on Staphylococcus aureus, and compounds 15 and 16
      showed inhibitory effects on Ralstonia solanacearum. Compounds 1-3, 7, 9, 11, 12,
      15 and 16 exhibited acetylcholinesterase inhibitory activity. A possible
      biogenetic pathway of compounds 1-16 was proposed to show the relationships
      between diepoxy-tetrahydro-2-(2-phenylethyl)chromones, epoxy-tetrahydro-2-(2
      phenylethyl) chromones, tetrahydro-2-(2-phenylethyl)chromones, and 2-(2
      phenylethyl)chromones of the flidersia type, the four main types of 2-(2
      phenylethyl)chromones found in agarwood, on the basis of their appearances in
      different stage of agarwood formation. 

PMID- 25068204
TI  - Agricultural biodiversity, social-ecological systems and sustainable diets.
AB  - The stark observation of the co-existence of undernourishment, nutrient
      deficiencies and overweight and obesity, the triple burden of malnutrition, is
      inviting us to reconsider health and nutrition as the primary goal and final
      endpoint of food systems. Agriculture and the food industry have made remarkable
      advances in the past decades. However, their development has not entirely
      fulfilled health and nutritional needs, and moreover, they have generated
      substantial collateral losses in agricultural biodiversity. Simultaneously,
      several regions are experiencing unprecedented weather events caused by climate
      change and habitat depletion, in turn putting at risk global food and nutrition
      security. This coincidence of food crises with increasing environmental
      degradation suggests an urgent need for novel analyses and new paradigms. The
      sustainable diets concept proposes a research and policy agenda that strives
      towards a sustainable use of human and natural resources for food and nutrition
      security, highlighting the preeminent role of consumers in defining sustainable
      options and the importance of biodiversity in nutrition. Food systems act as
      complex social-ecological systems, involving multiple interactions between human
      and natural components. Nutritional patterns and environment structure are
      interconnected in a mutual dynamic of changes. The systemic nature of these
      interactions calls for multidimensional approaches and integrated assessment and
      simulation tools to guide change. This paper proposes a review and conceptual
      modelling framework that articulate the synergies and tradeoffs between dietary
      diversity, widely recognised as key for healthy diets, and agricultural
      biodiversity and associated ecosystem functions, crucial resilience factors to
      climate and global changes. 

PMID- 25068203
TI  - Detection of pulmonary vasculopathy by novel analysis of oxygen uptake in
      patients with systemic sclerosis: association with pulmonary arterial pressures.
AB  - OBJECTIVES: During cardiopulmonary exercise testing (CPET) compromised pulmonary
      vasculature in patients with systemic sclerosis (SSc) may lead to increases in
      pulmonary arterial pressures (PAP) and decreased oxygen uptake. We hypothesised
      that this may lead into a disproportional heart rate (HR) increase with a
      corresponding V'O2/HR breakpoint and relates to systolic PAP at rest. METHODS: In
      a prospective design we evaluated V'O2/HR slopes for breakpoints. To understand
      its physiological meaning, we evaluated V'O2/HR and V'O2/mPAP slopes for
      breakpoints in a historic data set of SSc patients, in which CPET and right heart
      catheterisation was performed simultaneously. V'O2/HR slopes with a peak oxygen
      uptake outside the normal range were defined as pathologic. RESULTS: A breakpoint
      occurred in both V'O2/mPAP and V'O2/HR slope in 16/34 patients in the historic
      dataset and occurred in the V'O2/mPAP slope at a lower V'O2in 15 patients. In the
      prospective dataset, 73/121 patients showed a V'O2/HR breakpoint and achieved a
      significantly lower peak oxygen uptake compared to 48/121 patients without a
      V'O2/HR breakpoint (p=0.036). Mean systolic PAP in 41/121 patients with a
      pathologic V'O2/HR slope differed significantly from patients without a
      pathologic V'O2/HR slope (p=0.027). In 27/121 patients with a systolic PAP < 35
      mmHg a pathologic V'O2/HR slope was observed. CONCLUSIONS: SSc patients with a
      V'O2/HR breakpoint are characterised by a decreased oxygen uptake, likely caused
      by sudden PAP increases during exercise. Importantly, in patients with normal
      resting SPAP pathologic V'O2/HR slopes were observed. This suggests that these
      patients are at risk for developing pulmonary hypertension.

PMID- 25068205
TI  - Serum choline plasmalogens-those with oleic acid in sn-2-are biomarkers for
      coronary artery disease.
AB  - BACKGROUND: Identifying risk factors is crucial for preventing cardiovascular
      events, but there are no widely accepted predictive biomarkers. In our previous
      study of Japanese asymptomatic cohorts, we performed global analysis of serum
      ether glycerophospholipids (Egp) molecular profiles, and found that choline
      plasmalogens (PlsCho; 1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholine),
      particularly those containing oleic acid (18:1) in the sn-2 position, were
      strongly associated with a wide range of risk factors for metabolic
      syndrome/atherosclerosis. METHODS: We determined serum concentrations of Egp
      molecular species of coronary artery disease patients (n=50; 31 males and 19
      females) by LC/MS/MS, and plasmalogen (Pls; 1-O-alk-1'-enyl-2-acyl-sn
      glycerophospholipids) contents in lipoprotein fractions by HPLC using radioactive
      iodine. RESULTS: We found that the serum concentrations of ether choline
      glycerophospholipids (EgpCho), particularly PlsCho, were not only significantly
      lower in males with significant coronary stenosis but also associated with
      atherosclerosis-related parameters, and their association was stronger than
      either high-density lipoprotein cholesterol or adiponectin. In addition, serum
      PlsCho containing 18:1 or linoleic acid (18:2) in sn-2 showed the highest
      correlations with a wide range of atherogenic parameters among PlsCho molecular
      species. CONCLUSION: These results verify our previous findings that serum
      PlsCho, particularly those containing 18:1 in sn-2, may serve as reliable
      biomarkers for atherosclerosis.

PMID- 25068206
TI  - Assessment of pre-analytical and analytical variables affecting peptidome
      profiling of gingival crevicular fluid by MALDI-TOF mass spectrometry.
AB  - BACKGROUND: Gingival crevicular fluid (GCF) may be a source of new biomarkers of
      periodontitis/gingivitis. However, the minute volumes of GCF harvested in healthy
      sites are a serious drawback. We evaluated how pre-analytical and analytical
      variables concerning GCF collection and processing, could significantly influence
      quality and reproducibility of MALDI-TOF profiles. METHODS: GCF was collected
      from healthy sites. The use of paper strips vs paper points was compared.
      Peptides and proteins were extracted by centrifugal elution in different
      solutions, at different accelerations, with and without protease inhibitor
      cocktail (PIC). Finally, we evaluated how matrix composition and matrix/sample
      volume ratio affect the reproducibility of MALDI-TOF profiles. RESULTS:
      Trifluoroacetic acid elution generated richer gingival fingerprints compared to
      acetic acid, independently of the collection device. Centrifugation speed and PIC
      supplementation did not change GCF profiles. A fine modulation of matrix
      composition and matrix/sample volume ratio resulted in a satisfactory
      reproducibility (CV less than 10% for peak area and signal-to-noise ratio).
      CONCLUSION: An optimized procedure, enabling generation of reproducible MALDI-TOF
      profiles from limited volume of GCF, is proposed. These fingerprints may serve as
      reference for future studies oriented to the maintenance and preservation of good
      gingival status and to discovery biomarkers of periodontitis/gingivitis.

PMID- 25068207
TI  - Interpatient distributions of bloodspot area per fixed volume of application:
      comparison between filter paper and non-cellulose dried matrix spotting cards.
AB  - BACKGROUND: Non-cellulose dried matrix spotting (DMS) cards are an alternative to
      filter paper (FP) for bloodspots. We compared the interpatient distributions of
      bloodspot areas between DMS and FP for a fixed volume of application of whole
      blood, and examined correlations of areas with hematocrit. METHODS: EDTA-whole
      blood adult patient samples (n=49; 25 males, 24 females) were utilized after
      routine measurement of hemoglobin and hematocrit. Replicate (4*) bloodspots were
      produced by bolus drop application of 50MUL whole blood via a fixed-volume
      pipettor to either FP or DMS. Dried bloodspot areas were determined by image
      analysis. RESULTS: Hematocrits (HCT) were normally distributed (HCT=30.9+/-5.3%).
      For both FP and DMS, bloodspot areas (a, cm(2)) across patients were normally
      distributed: for FP, a=1.11+/-0.056cm(2) (+/-5.0%); for DMS, a=0.378+/-0.037cm(2)
      (+/-9.9%). Relative bloodspot area differences across the population range were
      >20% for both DMS and FP. Correlation of bloodspot areas to hematocrit was
      negative for FP (r=-0.80) but positive for DMS (r=+0.78). CONCLUSIONS:
      Interpatient variation in blood volume per area is a preanalytical variable for
      both DMS and FP bloodspots. Hematocrit is but one interpatient variable, as
      correlations of fixed-volume bloodspot areas with hematocrit across patients were
      substantially inexact (r(2)<0.65).

PMID- 25068209
TI  - Exploring the consequences of mitochondrial differences arising through
      hybridization of sunfish.
AB  - Previous studies have shown evidence of genomic incompatibility and mitochondrial
      enzyme dysfunction in hybrids of bluegill (Lepomis macrochirus Rafinesque) and
      pumpkinseed (Lepomis gibbosus Linnaeus) sunfish (Davies et al., 2012 Physiol.
      Biochem. Zool. 85, 321-331). We assessed if these differences in mitochondria had
      an impact on metabolic processes that depend on mitochondrial function,
      specifically hypoxia tolerance and recovery from burst exercise. Bluegill,
      pumpkinseed, and their hybrids showed no difference in the critical oxygen
      tension (Pcrit) and no differences in tissue metabolites measured after exposure
      to 10% O2 for 30min. In contrast, loss of equilibrium (LOE) measurements showed
      that hybrids had reduced hypoxia tolerance and lacked the size-dependence in
      hypoxia tolerance seen in the parental species. However, we found no evidence of
      systematic differences in metabolite levels in fish after LOE. Furthermore, there
      were abundant glycogen reserves at the point of loss of equilibrium. The three
      genotypes did not differ in metabolite status at rest, showed an equal disruption
      at exhaustion, and similar metabolic profiles throughout recovery. Thus, we found
      no evidence of a mitochondria dysfunction in hybrids, and mitochondrial
      differences and oxidative metabolism did not explain the variation in hypoxia
      tolerance seen in the hybrid and two parental species.

PMID- 25068208
TI  - Near-euglycemia can be achieved safely in pediatric total pancreatectomy islet
      autotransplant recipients using an adapted intravenous insulin infusion protocol.
AB  - BACKGROUND: Children with severe chronic pancreatitis may undergo total
      pancreatectomy with islet autotransplantation (TPIAT) to relieve pain while
      minimizing the risk of postsurgical diabetes. Because overstimulation of
      transplanted islets by hyperglycemia can result in beta-cell loss, we developed a
      specialized intravenous insulin infusion protocol (IIP) for pediatric TPIAT
      recipients to maintain euglycemia or near-euglycemia posttransplant. SUBJECTS AND
      METHODS: Our objective was to review glucose control using an IIP specific for
      TPIAT recipients at a single institution. We reviewed postoperative blood glucose
      (BG) levels for 32 children 4-18 years old with chronic pancreatitis who
      underwent TPIAT between July 2011 and June 2013. We analyzed the proportion of BG
      values in the range of 70-140 mg/dL, mean glucose, glucose variability, and
      occurrence of hypoglycemia during the IIP; we also evaluated the transition to
      subcutaneous therapy (first 72 h with multiple daily injections [MDI]). RESULTS:
      During IIP, the mean patient BG level was 116+/-27 mg/dL, with 83.1% of all
      values in the range of 70-140 mg/dL. Hypoglycemia was rare, with only 2.5% of
      values <70 mg/dL. The more recent era (n=16) had a lower mean BG and less
      variability than the early era (first 16 patients) (P<=0.004). Mean glucose level
      (116 vs. 128 mg/dL) and glucose variability were significantly lower during the
      IIP compared with MDI therapy (P<0.0001). CONCLUSIONS: Tight glycemic control
      without excessive severe hypoglycemia was achieved in children undergoing TPIAT
      using an IIP specifically designed for this population; the ability to maintain
      BG in target range improved with experience with the protocol.

PMID- 25068210
TI  - An organocatalytic cascade reaction of 2-nitrocyclohexanone and alpha,beta
      unsaturated aldehydes with unusual regioselectivity.
AB  - An organocatalytic cascade reaction of 2-nitrocyclohexanone and alpha,beta
      unsaturated aldehydes was developed. Bicyclo[3.3.1]nonanone products were
      obtained with good yields and excellent enantioselectivities. The reaction
      occurred with unusual regioselectivity. A dienolate-iminium activation mechanism
      was proposed. The products were transformed to eight-membered cyclic ketones with
      high enantioselectivity. 

PMID- 25068211
TI  - Controlled heterogeneous stem cell differentiation on a shape memory hydrogel
      surface.
AB  - The success of stem cell therapies is highly dependent on the ability to control
      their programmed differentiation. So far, it is commonly believed that the
      differentiation behavior of stem cells is supposed to be identical when they are
      cultured on the same homogeneous platform. However, in this report, we show that
      this is not always true. By utilizing a double-ion-triggered shape memory effect,
      the pre-seeded hMSCs were controllably located in different growth positions.
      Here, we demonstrate for the first time that the differentiation behavior of
      hMSCs is highly sensitive to their growth position on a hydrogel scaffold. This
      work will not only enrich the mechanisms for controlling the differentiation of
      stem cells, but also offer a one-of-a-kind platform to achieve a heterogeneously
      differentiated stem cell-seeded hydrogel scaffold for complex biological
      applications. 

PMID- 25068212
TI  - Medical support at a large-scale motorsports mass-gathering event: the inaugural
      Formula One United States Grand Prix in Austin, Texas.
AB  - INTRODUCTION: Formula One returned to the United States on November 16-18, 2012,
      with the inaugural United States Grand Prix in Austin, Texas. Medical
      preparedness for motorsports events represents a unique challenge due to the
      potential for a high number of spectators seeking medical attention, and the
      possibility for a mass-casualty situation. Adequate preparation requires close
      collaboration across public safety agencies and hospital networks to minimize
      impact on Emergency Medical Services (EMS) resources. HYPOTHESIS/PROBLEM: To
      report the details of preparation for an inaugural mass-gathering motorsports
      event, and to describe the details of the medical care rendered during the 3-day
      event. METHODS: A retrospective analysis was completed utilizing postevent
      summaries, provided by the medical planning committee, by the Federation
      Internationale de L'Automobile (FIA), and Austin Travis County Emergency Medical
      Services (ATCEMS). Patient data were collected from standardized patient care
      records for descriptive analysis. Medical usage rates (MURs) are reported as a
      rate of patients per 10,000 (PPTT) participants. RESULTS: A total of 566 patients
      received medical care over the 3-day period with the on-site care rate of 95%.
      Overall, MUR was 21.3 PPTT attendees. Most patients had minor problems, and there
      were no driver injuries or deaths. CONCLUSION: This mass-gathering motorsport
      event had a moderate number of patients requiring medical attention. The
      preparedness plan was implemented successfully with minimal impact on EMS
      resources and local medical facilities. This medical preparedness plan may serve
      as a model to other cities preparing for an inaugural motorsports event.

PMID- 25068213
TI  - Opioid drug addiction and pain: diagnostic and management challenges.

PMID- 25068214
TI  - Experimental jaw muscle pain increases pain scores and jaw movement variability
      in higher pain catastrophizers.
AB  - AIMS: To investigate differences between higher and lower pain catastrophizers in
      the effects of hypertonic saline-evoked jaw muscle pain on pain perception and
      jaw movement. METHODS: Repetitive open/close jaw movements were recorded in 28
      asymptomatic participants (20 men, 8 women; ages 25 to 62 years) during
      continuous infusion of 5% hypertonic saline or isotonic saline into the right
      masseter muscle. All participants completed the McGill Pain Questionnaire; the
      Depression, Anxiety and Stress Scales; and the Jaw Function Limitation Scale.
      They were divided into two groups depending on the median Pain Catastrophizing
      Scale score. Statistical analyses involved multivariate analysis of variance,
      independent samples or paired t tests, and Pearson correlations (statistical
      alpha: P < .05). RESULTS: Pain intensity, unpleasantness, perceived area, and
      pain rating indices were significantly (P < .05) elevated in higher pain
      catastrophizers during hypertonic saline-evoked pain in comparison with lower
      catastrophizers. The higher catastrophizers exhibited significantly (P < .05)
      slower jaw velocity than the lower catastrophizers during hypertonic saline
      infusion in comparison with IS infusion. In comparison with lower
      catastrophizers, there was a significantly greater change in the percentage of
      coefficient of variation between hypertonic saline and isotonic saline infusions
      in higher catastrophizers for closing velocity and opening and closing amplitude.
      CONCLUSION: The increased reported pain intensity, pain areas, and pain rating
      indices are consistent with enhanced central sensitization processes in high
      catastrophizing individuals. The slower velocity and greater variability of
      repetitive jaw movements in higher pain catastrophizing individuals in acute
      experimental pain may reflect changes in motor coordination as an example of
      avoidance behavior for the jaw motor system.

PMID- 25068215
TI  - A systematic review and meta-analysis of usual treatment versus psychosocial
      interventions in the treatment of myofascial temporomandibular disorder pain.
AB  - AIMS: To carry out a systematic review and meta-analysis comparing the effects of
      occlusal splint therapy ("usual treatment") and psychosocial interventions for
      the treatment of myofascial temporomandibular disorder (TMD) pain in adult
      patients. METHODS: Independent screening and evaluation of randomized clinical
      trials included comparisons between "usual treatment" based on splint therapy and
      psychosocial interventions for TMD treatment within electronic databases
      (PubMed/MEDLINE, CENTRAL, EMBASE), ongoing trials databases (Current Controlled
      Trials, ClinicalTrials.gov), and additional sources. The outcomes selected for
      the systematic review were self-reported pain, pain interference, unassisted jaw
      opening without pain, muscle pain upon palpation, depression, and somatization.
      The effect measures were analyzed using a random-effect model (Review Manager
      computer program). RESULTS: The outcomes "longterm self-reported pain" and "long
      term depression" were significantly different for the comparisons of "usual
      treatment" and psychosocial interventions, and they favored the latter (P < .005
      and P < .05, respectively). These results must be viewed with caution due to the
      limited number of studies available. A tendency toward greater improvements of
      psychological outcomes was observed for psychosocial interventions, while
      physical functioning was slightly more responsive to "usual treatment."
      CONCLUSION: No evidence was found to distinguish the clinical effectiveness
      between "usual treatment" and psychosocial interventions for myofascial TMD pain.
      Future studies of TMD and related subdiagnoses should be reported according to
      core standardized outcomes to facilitate comparisons.

PMID- 25068216
TI  - Beliefs and distress about orofacial pain: patient journey through a specialist
      pain consultation.
AB  - AIMS: To explore patients' understanding of their orofacial pain, as this is an
      under-researched area despite emerging as a common aim of consultation. METHODS:
      Twelve people with chronic orofacial pain were interviewed shortly before their
      first consultation at a specialist facial pain clinic about their understanding
      of their pain, and they completed self-report measures of distress and pain
      interference. A day after the consultation, they wrote a short letter about how
      they now understood their pain and were then interviewed by phone. All accounts
      were analyzed using thematic analysis. RESULTS: Four themes emerged across
      preconsultation and postconsultation data: the need for information to counteract
      helplessness; worry as part of making sense of pain; validation of the pain
      experience (all predominant preconsultation); and the importance of trust
      (reflecting changes in understanding since consultation). Most patients changed
      their understanding of pain and resolved their worries to some extent, and they
      reported reduced distress and less interference. CONCLUSION: Patients' fears and
      beliefs about chronic orofacial pain are dominated by worrying and searching for
      meaning before consultation. Information about their chronic pain condition
      counters feelings of helplessness and supports sense-making around pain when
      explanations are clear, are delivered sensitively from a trusted source, and take
      into account the patient's existing health beliefs; this promotes self
      management. These findings underline the important functions of specialist
      consultation in achieving a shared accurate understanding of pain and options for
      treatment.

PMID- 25068217
TI  - A comparative analysis of magnetic resonance imaging and radiographic
      examinations of patients with atypical odontalgia.
AB  - AIMS: To examine (1) the occurrence of magnetic resonance imaging (MRI) signal
      changes in the painful regions of patients with atypical odontalgia (AO) and (2)
      the correlation of such findings to periapical bone defects detected with a
      comprehensive radiographic examination including cone beam computed tomography
      (CBCT). METHODS: A total of 20 patients (mean age 52 years, range 34 to 65)
      diagnosed with AO participated. Mean pain intensity (+/- standard deviation) was
      5.6 +/- 1.8 on a 0-10 numerical rating scale, and mean pain duration was 4.3 +/-
      5.2 years. The inclusion criterion was chronic pain (> 6 months) located in a
      region with no clear pathologic cause identified clinically or in periapical
      radiographs. In addition to a clinical examination and a self-report
      questionnaire, the assessments included radiographic examinations (panoramic,
      periapical, and CBCT images), and an MRI examination. Changes in MRI signal in
      the painful region were recorded. Spearman's rank correlation between
      radiographic and MRI findings was calculated. RESULTS: Eight of the patients
      (40%) had MRI signal changes in the pain region. The correlation to radiographic
      periapical radiolucencies was 0.526 (P = .003). Of the eight teeth displaying
      changes in MRI signal, six showed periapical radiolucency in the radiographs.
      CONCLUSION: MRI examination revealed no changes in the painful region in a
      majority of patients with AO, suggesting that inflammation was not present. MRI
      findings were significantly correlated to radiographic findings.

PMID- 25068218
TI  - "Grin(d) and bear it": narratives from Sami women with and without
      temporomandibular disorders. A qualitative study.
AB  - AIMS: To explore thoughts, experiences, and beliefs regarding temporomandibular
      disorders (TMD) among Sami women with and without TMD in order to gain insights
      into their health care experiences and to generate a hypothesis regarding factors
      associated with long-standing TMD. METHODS: Qualitative thematic interviews were
      conducted with a strategic sample of 17 Sami women, of whom 10 had a TMD
      diagnosis according to the Research Diagnostic Criteria for TMD and 7 age-matched
      women who had no signs or symptoms of TMD. Their ages were between 23 and 58
      years. The thematic interviews were audiotaped, transcribed verbatim, and
      analyzed based on Grounded Theory, a qualitative methodology aiming to generate
      hypotheses grounded in the gathered data. RESULTS: The core category that evolved
      was "Grin(d) and bear it," which summarizes the Sami participants' various ways
      and stages of processing and handling the interacting categories (triggers,
      strains, distrust, and reconciliation with pain and/or difficulties in life).
      They described divergent as well as similar understandings of triggering factors.
      Maintaining factors were described as mental-physical strain and stress, and also
      a jaw-clenching behavior. Women without TMD contributed with factors that helped
      them to handle strains, reconcile, and stay healthy. They relied on strong social
      support. CONCLUSION: Based on the analysis, the following hypothesis was
      generated: Women with TMD, associated headaches, and neck-shoulder pain may
      benefit from efforts aimed at empowering them to use their own abilities to
      reduce stress behavior, strain, and disuse of the jaw. Rehabilitation strategies
      in groups might increase their sense of coherence and increase social support,
      which seems to be more limited than in women with no symptoms of TMD.

PMID- 25068219
TI  - Effects of muscle pain induced by glutamate injections during sustained clenching
      on the contraction pattern of masticatory muscles.
AB  - AIMS: To evaluate the contraction pattern of masticatory muscles during sustained
      clenching tasks with or without experimental pain induced by glutamate injection
      into the masseter muscle. It was hypothesized that acute muscle pain could induce
      compensatory changes in the electromyographic (EMG) activity of the masticatory
      muscles. METHODS: Fifteen volunteers (seven males, mean age +/- SD = 29.7 +/- 1.1
      years; eight females, mean age +/- SD = 23.5 +/- 1.2 years) were recruited in a
      crossover experimental study. All subjects participated in two randomized 20
      minute experimental sessions. Each subject was asked to clench at 25% of the
      maximum voluntary contraction (MVC). After 10 minutes, isotonic saline or
      glutamate was injected in random order into the right masseter. EMG activity
      (root mean square [RMS] and mean power frequency [MPF]) was assessed in the
      masseter and anterior temporalis muscles on both sides. Pain and fatigue were
      assessed by 0-10 numeric rating scales (NRS) every minute. Differences between
      conditions (isotonic saline vs glutamate) for all the outcome parameters were
      analyzed by using a mixed effect model. RESULTS: The EMG activity of the
      masticatory muscles and pain and fatigue scores were not dependent on isotonic
      saline/glutamate injection (all P > .05). The RMS in the temporalis and masseter
      muscles increased with time (right masseter P = 0.001, left masseter P = .004,
      right temporalis P = .22, left temporalis P = .006), whereas the MPF decreased
      (right masseter P = .0001, left masseter P < .0001, right temporalis P = .51,
      left temporalis P = .0005). Scores for fatigue and pain increased during the
      experimental sessions (all P < .05). CONCLUSION: Intramuscular injection of
      glutamate caused more pain than isotonic saline but did not affect the
      contraction pattern of the masticatory muscles during a sustained clenching task.
      This finding strongly suggests the adaptive capacity of the stomatognathic system
      in the presence of acute nociceptive inputs.

PMID- 25068221
TI  - Effects of chemically induced hypoxia on in vitro expression of hypoxia inducible
      factor-lalpha, vascular endothelial growth factor, aggrecanase-1, and tissue
      inhibitor of metalloproteinase-3 in rat mandibular condylar chondrocytes.
AB  - AIMS: To examine the expression of hypoxia inducible factor-lalpha (HIF-1alpha),
      vascular endothelial growth factor (VEGF), aggrecanase-1 (ADAMTS-4), and tissue
      inhibitor of metalloproteinase-3 (TIMP-3) in rat mandibular condylar chondrocytes
      under hypoxic conditions and examine the relationship of these expressed factors
      in early condylar cartilage growth. METHODS: CoCl2 was used to mimic a hypoxic
      microenvironment by chemically inducing hypoxia. Chondrocytes, which were
      obtained from the mandibular condyles of 3-week-old female Sprague-Dawley rats,
      were treated with 125 MUmol/L CoCl2 for 48 hours. The HIF-1alpha, VEGF, ADAMTS-4,
      and TIMP-3 mRNA levels in chondrocytes were detected using a
      semiquantitativepolymerase chain reaction (PCR) at 12, 24, and 48 hours after the
      initiation of hypoxia and normoxia conditions. A univariate variance analysis
      (pairwise least significant difference t test) using a SPSS 13.0 software package
      was performed to test for differences between different groups. RESULTS: PCR
      analysis of the chondrocytes showed that the expression of HIF-1alpha and VEGF
      mRNA increased at 12, 24, and 48 hours after induction of hypoxia. HIF-1alpha
      expression gradually increased throughout the study duration, while VEGF
      expression peaked at 12 hours. Compared to normoxia conditions, hypoxia resulted
      in constantly elevated expression levels of both. On the other hand, there was no
      significant difference in the ADAMTS-4 and TIMP-3 mRNA expression between hypoxic
      and normoxic conditions throughout the study (P > .05). CONCLUSION: An
      upregulated HIF-1alpha and VEGF mRNA expression indicates their important roles
      in cartilage vascularization and development in newly hypoxic microenvironments.
      Additionally, chemically induced hypoxia has little effect on the expressions of
      ADAMTS-4 and TIMP-3.

PMID- 25068220
TI  - Effects of low-intensity pulsed ultrasound on the expression of cyclooxygenase-2
      in mandibular condylar chondrocytes.
AB  - AIMS: To determine the effect of low-intensity pulsed ultrasound (LIPUS) on
      cyclooxygenase-2 (COX-2) expression and related mechanisms by using cultured
      articular chondrocytes derived from porcine mandibular condyles after treatment
      with interleukin-1 beta (IL-1beta). METHODS: Chondrocytes were derived from
      porcine mandibular condylar cartilage and cultured. The cells were treated with
      or without 10 ng/mL IL-1beta. At the same time, the cells were exposed to LIPUS
      for 20 minutes. After LIPUS exposure, the conditioned medium was changed to a
      fresh one without IL-1beta, and the cells were incubated for 0 to 24 hours. The
      effects of LIPUS on IL-1beta-treated chondrocytes were examined in terms of the
      expression of p-integrin beta1, COX-2, and phosphorylated extracellular signal
      related kinase (p-ERK) 1/2 by real-time polymerase chain reaction (PCR) and
      Western blot analyses. Differences in the means among multiple groups were
      examined by one-way analysis of variance (ANOVA) for all groups at each time
      point, followed by a Scheffe multiple comparison test as a post-hoc test; Student
      t test was also used. RESULTS: COX-2 mRNA level was upregulated by the treatment
      with IL-1beta and was suppressed significantly (P < .01) by LIPUS exposure.
      Furthermore, LIPUS enhanced gene expression and phosphorylation of integrin beta,
      and it inhibited the expression of p-ERK 1/2. CONCLUSION: LIPUS exposure
      inhibited IL-1beta-induced COX-2 expression through the integrin beta1 receptor
      followed by the phosphorylation of ERK 1/2. Despite the restricted duration of
      its effect, LIPUS is suggested to be a potential candidate as a preventive and
      auxiliary treatment to suppress the degradation of articular chondrocytes in
      temporomandibular joint osteoarthritis.

PMID- 25068222
TI  - Periorbital pain induced by the concha bullosa fungus ball: a case report.
AB  - Concha bullosa is characterized by pneumatization of the middle turbinate and is
      one of the most common variations of the sinonasal anatomy. It is most often
      asymptomatic. A fungus ball in the concha bullosa is extremely rare, with only
      two reported cases in the English literature. This article describes a patient
      with such a fungus ball in the concha bullosa that caused right periorbital pain,
      specifically in the right medial canthal area, similar to mucosal contact point
      headache. 

PMID- 25068223
TI  - Rebound in QuantiFERON-TB Gold In-Tube response after active tuberculosis
      treatment.

PMID- 25068224
TI  - Overview on non-melanoma skin cancers in solid organ transplant recipients.
AB  - The risk of non-melanoma skin cancer (NMSC) is significantly increased in solid
      organ transplant recipients (SOTRs) due to the long-term immunosuppressive
      treatment. NMSCs can be more aggressive in SOTRs than in the general population,
      resulting in significantly higher morbidity and mortality. In contrast to the
      immunocompetent population, skin cancers in SOTRs are dominated by squamous cell
      carcinoma, followed by basal cell carcinoma. Life-long radiation exposure, male
      sex, fair skin, history of prior NMSC, genetic factors, age at transplant along
      with duration and extent of the immunosuppression therapy have been identified as
      risk factors for NMSC in SOTRs. Photo-protection, skin self-examination, early
      diagnosis and treatment of skin lesions, reduction of immunotherapy, switch to
      mammalian target-of-rapamycin inhibitors and chemoprevention with oral retinoids
      are effective measures for the reduction of the incidence of NMSC in such
      patients. 

PMID- 25068225
TI  - Cutaneous melanoma in solid organ transplant patients.
AB  - Solid organ transplant patients are at greatly increased risk of developing a
      wide variety of skin cancers, particularly epithelial skin cancers. On the other
      hand, it is well known that an intact immune system limits the development of
      benign melanocytic lesions. The eruptive nevi phenomenon, which we can observe in
      solid organ transplant recipients, is indicative of the relationship between
      melanocyte proliferation and immune system. Regression of melanocytic nevi after
      restoration of complete immune responsiveness is a further clinical example the
      role of immunosurveillance on melanocyte proliferation. However, melanoma
      incidence in organ transplant recipients appears only 2-3 folds higher than in
      general population. To this regard, organ transplant recipients who develop de
      novo melanomas thicker than 2mm seem to have a significantly worse outcome with a
      greatly increased risk of dying of metastatic melanoma, whereas those who develop
      a <=2 mm thickness melanoma seem to have a prognosis similar to that of the
      general population. Furthermore, there is no evidence supporting an increased
      risk of melanoma recurrences after transplant in patients with a history of low
      risk melanoma. Melanoma is also one of the most frequent and lethal donor-derived
      malignancies suggesting that a history of invasive melanoma should be considered
      an absolute contraindication to donation. The aim of this review is to
      investigate the relationship between immunosuppression and melanoma and to
      discuss its clinical implications for the management of transplant-associated
      melanoma. 

PMID- 25068226
TI  - Kaposi's sarcoma and other rare skin cancers in organ transplant patients.
AB  - Kaposi's sarcoma and Merkel cell carcinoma represent potentially lethal cutaneous
      complications in organ transplanted patients. These neoplasms can severely
      complicate the clinical outcome of transplanted patient. Moreover, as the
      diagnosis is mainly clinical, a knowledge of these clinical entities may be
      fundamental in the daily management of this group of patients. In this review we
      will discuss these neoplasms in relation to the role of immunosuppression in
      their onset and progression. 

PMID- 25068227
TI  - Cutaneous lymphoproliferative disorders in organ transplant recipients: update
      2014.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are lymphoid or plasmacytic
      proliferations that develop after solid organ, bone marrow or stem cell
      transplantation. PTLD are the leading cause of cancer-related mortality and graft
      loss in both pediatric and adult solid organ transplant recipients (ORT). These
      disorders comprise a spectrum ranging from usually EBV-driven, mostly B-cell
      polyclonal proliferations to B- and T-cell lymphomas indistinguishable from their
      counterparts occurring in immunocompetent individuals. PTLD usually present in
      extranodal sites; isolated skin involvement of PTLD is rare. A recent multicenter
      European case series showed that primary cutaneous T-cell PTLD are more common
      than primary cutaneous B-cell PTLD, and along with its folliculotropic variant,
      mycosis fungoides (MF) is the most frequent form of posttransplant primary
      cutaneous T-cell lymphoma (CTCL). This case series also disclosed that primary
      cutaneous CD30+ lymphoproliferative disorders is the second most common
      posttransplant CTCL subtype, indicating that the spectrum of primary CTCL in OTR
      is similar to that in the general population. However, in contrast with the
      immunocompetent individuals, the prognosis of primary cutaneous CD30+ anaplastic
      large T-cell lymphoma is worse than posttransplant MF and than its counterpart in
      the general population which has an excellent prognosis. The recent case series
      indicated that the spectrum of primary cutaneous B-cell PTLD differs
      significantly from cutaneous B-cell lymphoma in the general population, with a
      predominance of EBV-associated forms. Currently, the best therapeutic
      intervention(s) for primary cutaneous PTLD remains unknown. 

PMID- 25068228
TI  - Cutaneous viral infections in organ transplant patients.
AB  - Cutaneous infections might occur in up to 80% of organ transplant recipients
      (OTR) and viral infections are the most common them. The risk of different skin
      infection is among related to the intensity of immunosuppression. During the
      first post-transplant period, herpes viruses are most common. After some months
      following transplantation, human papilloma viruses represent the most significant
      infections among OTR. Reactivation of herpes simplex virus in OTR can become more
      invasive, takes longer to heal, and shows greater potential for dissemination to
      visceral organs compared to the general population. Specific immunosuppressive
      drugs (namely muromonab and mycophenolate mofetil) have been associated with an
      increased risk of herpes virus reactivation after transplantation. On the other
      hand, there is evidence that the mTOR inhibitors, such as everolimus, may be
      associated with a decreased incidence of herpesvirus infections in transplant
      recipients. The incidence of herpes zoster in OTR is 10 to 100 fold higher than
      the general population, ranging from 1% to 12%. The chronic immunosuppression
      performed in OTR may lead to persistent replication of herpesviruses,
      dissemination of the virus with multivisceral involvement (hepatitis,
      pneumonitis, myocarditis, encephalitis and disseminated intravascular
      coagulation) and eventually, the emergence of antiviral-drug resistance. Viral
      warts are the most common cutaneous infection occurring in OTR. The number of
      warts increases with the duration of immunosuppressive therapy. Since warts in
      organ recipients are frequently multiple and only rarely undergo spontaneous
      regression, the therapeutic management of warts in patients treated with
      immunosuppressive drugs might be challenging. Imiquimod, 1% cidofovir ointment,
      acitretin proved to be useful off-label strategies for recalcitrant cutaneous
      viral warts in OTR. Extensive and atypical presentation of molluscum contagiosum
      has been also reported in OTR, with a prevalence between 3% to 6.9%. Giant
      molluscum contagiosum is a clinical variant in which large nodule greater than
      0.5-1 cm in diameter are observed.

PMID- 25068229
TI  - Opportunistic deep cutaneous mycoses in solid organ transplant recipients.
AB  - Invasive fungal infections are a major cause of morbidity and mortality among
      organ transplant recipients, despite many progresses concerning diagnosis,
      preventions and treatment. Risk factors for invasive fungal infections in
      transplanted recipients include type and severity of immunosuppression,
      especially in life-saving organs as lung or liver, older age at transplantation,
      and technical complexity of surgery, living in endemic areas or exposure to a
      contaminated environment. Superficial fungal infections are caused by Candida,
      Dermatophytes, and Malassezia. In invasive mycoses, skin lesions may occur as a
      consequence of the systemic dissemination of invasive mycoses, or after direct
      inoculation in the skin. Aspergillosis, cryptococcosis, Zygomycoses, dark mould
      infections, fusariosis and infections attributable to Scedosporium and
      Pseudallescheria species are the most common etiological agents. Cutaneous
      manifestations of fungal infection are not specific, and a high degree of
      suspicion is required, and prompt biopsy for histology and culture is needed.
      Therapy with lyposomal amphotericin B and new triazoles are effective. 

PMID- 25068230
TI  - Basal cell carcinoma: differences according to anatomic location and clinical
      pathological subtypes.
AB  - AIM: Basal cell carcinoma (BCC) is the most common skin malignant neoplasm in
      humans. Its localization and its clinical-pathological aspects are fundamental
      for the treatment and the outcome of these tumors. We wanted to verify if
      different clinical-pathological subtypes of BCC may be present with different
      frequencies on single skin areas. METHODS: Three hundred six patients affected by
      BCC seen in Sant'Andrea Hospital, U.O.C. Dermatology, NESMOS Department, Faculty
      of Medicine, University of Rome "Sapienza", from January 2008 to December 2010,
      were retrospectively included in this study. Findings from all patients were
      tabulated and analyzed to characterize the clinical-pathological aspects of BCC
      according to their anatomic localization. We considered the following clinical
      subtypes of BCC, nodular, superficial, sclerodermiform, pearly and ulcerative.
      RESULTS: One hundred ninety-seven out of 306 patients (64.4%) were localized on
      the head, 6 (1.9%) on the neck, 73 patients (23.9%) on the trunk, 2 (0.6%) on the
      perineum, 4 (1.3%) on upper limbs and 24 (7.9%) on legs. On the head BCC were
      mostly nodular (44.7%). On the trunk they were mostly superficial (34.3%). BCC on
      legs were ulcerative in all the 24 patients. CONCLUSION: Our data confirm that
      BCC may have different clinical-pathological aspects on single skin areas.
      Interestingly in our casistic BCC on the legs were present in an uncommon high
      percentage. They presented as ulcerative lesions and this fact leads to conclude
      that in every patient presenting a chronic ulcer on the leg with difficulty to be
      cured a biopsy is mandatory to put in evidence the possible presence of BCC and
      consequently to perform the correct surgical treatment to obtain a complete
      response for the patient.

PMID- 25068231
TI  - Effect of intradermal injection of heparinase III on skin wound healing in
      diabetic rats.
AB  - AIM: neuropathy and vascular damage in this disease. Heparanase is an
      endoglycosidase that degrades heparan sulfate in the extracellular matrix and is
      believed to promote angiogenesis. The present study has been performed to
      investigate the effect of heparinase III (an enzyme which exclusively cleaves
      heparan sulfate) on wound healing in diabetic rats. METHODS: The rats became
      diabetic by a single streptozotocin injection. Two weeks later, a wound was
      created by excision of the skin in the left paravertebral area. Heparinase III
      (0.2 unit) was injected intradermally around the wound every 5 days, starting on
      day one, for a total of three doses. The wound area was measured every 3 days.
      After completion of wound healing, full thickness skin samples were taken from
      the wound sites and evaluated for volume density of the collagen bundles,
      numerical density of the fibroblasts, and length density of the vessels. RESULTS:
      Heparinase III accelerated wound closure compared to control diabetic animals.
      Microscopical examination revealed that it increased angiogenesis with no
      significant effect on collagen density and the number of fibroblasts. CONCLUSION:
      Heparinase III induces angiogenesis and improves wound healing in diabetic animal
      model.

PMID- 25068232
TI  - Clinical evaluation and assessment of the therapeutic efficacy of alitretinoin in
      a group of patients with chronic hand eczema refractory to topical steroid
      therapy.
AB  - AIM: We examined and evaluated the clinical characteristics of patients who had
      come to the Allergological and Occupational Dermatology unit in Florence with
      severe CHE refractory to potent topical corticosteroids. We evaluated the
      efficacy and safety of alitretinoin and we analyzed the response in the three
      months of follow-up in the group of patients who completed the cycle of therapy.
      Improvement in clinical signs and symptoms was assessed using mTLSS and PGA.
      METHODS: All patients were treated daily with single 30-mg doses of oral
      alitretinoin for 3 to 5 months. The study examined 15 patients with a clinical
      diagnosis of severe CHE. We found the treatment to be efficient in nine of 13
      patients (69%) who were assessed as having "clear" or "almost clear" hands
      according to PGA. RESULTS AND CONCLUSION: Even if the number of patients we
      analyzed was limited and lacked a control group the study allowed us to confirm
      the efficacy of alitretinoin used in a "real life" clinical experience. In
      addition, thanks to the adoption of proper emollient therapy and avoidance of any
      relevant allergens or irritants, no recurrence of the condition was observed
      among the patients who completed therapy with a PGA value of "mild", "almost
      clear", or "clear" during three months after treatment.

PMID- 25068233
TI  - A dietary supplement to reduce side effects of oral isotretinoin therapy in acne
      patients.
AB  - AIM: The purpose of the study was to analyze the potential capacity of a dietary
      supplement, based on gamma linolenic acid, vitamin E, vitamin C, beta-carotene,
      coenzyme Q10 and Vitis Vitifera, to reduce side effects, in particular the dry
      skin, erythema and desquamation, due to treatment with oral isotretinoin, and
      evaluate the ability of the product to increase adherence to therapy in patients
      with acne. METHODS: Forty-eight patients with nodular acne (32 females and 16
      males) were randomly divided into 2 groups: 24 received isotretinoin therapy (20
      30 mg/day) for 6 months associated to dietary supplement (twice a day), while the
      other 24 patients received only isotretinoin (20-30 mg/day) for 6 months. For all
      patients the degree of acne severity, through GAGS (Global Acne Grading System),
      the sebum production by Sebutape, the hydration by Corneometer and the erythema
      by Mexameter, were measured. We have also evaluated the adherence to treatment,
      asking to patients how many days a week they follow the therapy. RESULTS:
      Patients treated with dietary supplement had lower side effects, with a less
      degree of erythema and dryness, and greater degree of hydration; a greater
      adherence to therapy was also reported. CONCLUSION: Thanks to antioxidant and
      moisturizing properties, the dietary supplement containing gamma linolenic acid,
      vitamin E, vitamin C, betacarotene, coenzyme Q10 and Vitis Vitifera, can be
      considered a useful supplement in the treatment and prevention of dry skin
      associated with the use of oral isotretinoin.

PMID- 25068234
TI  - Body dysmorphic disorder: beyond skin deep.
AB  - Body dysmorphic disorder (BDD) is a psychiatric illness that primarily affects
      adolescents and young adults of both sexes. Patients have a distorted self-image,
      which manifests as a preoccupation with slight or imagined defects in the face,
      nose, skin, hair or any part of the body that ultimately interferes with daily
      functioning. It is a relatively common yet long unrecognized problem. Patients
      often seek multiple physician assessments for their perceived defects and request
      cosmetic procedures. Early intervention can prevent a cycle of multiple
      surgeries, as the outcome is usually poor and may lead to exacerbation of
      symptoms, anger and litigation. BDD is a disabling, and even life-threatening,
      condition; it can lead to major depression and suicidal ideation. Selective
      serotonin reuptake inhibitors and cognitive behavioral therapy are the mainstay
      of treatment and are beneficial in most patients. A multidisciplinary approach is
      strongly recommended. 

PMID- 25068235
TI  - Fusidic acid in skin infections and infected atopic eczema.
AB  - Skin infections represent an important public health issue and cost-driver.
      Additionally, chronic skin lesions are sometimes colonized by Gram-negative
      species. Topical therapies are a key component in the management of mild-to
      moderate skin infections. In such cases, topical antibiotics may be preferable to
      systemic treatment, since they maximize the effective doses at the site of
      infection while minimizing the systemic side effects of the drugs. However, the
      prevalence of resistant strains is steadily increasing and cases of sensitization
      are not uncommon. As a consequence, the ideal topical antibiotic should be
      selective (thus, minimizing cross-resistance), have weak sensitization potential,
      penetrate the skin efficiently, reach adequate local doses at the site of
      infection, and finally be available in different formulations matching patients'
      preferences and needs. Fusidic acid (FA) is a selective antibiotic available in
      several topical formulations. Pharmacokinetic and pharmacodynamic studies have
      shown that, contrary to other topical antibiotics such as gentamicin or
      mupirocin, FA reaches high antimicrobial concentration at deep skin layers after
      topical application either on intact or damaged epidermis. Several randomized
      controlled trials demonstrated that FA, in its various topical formulations, is
      very effective in treating skin infections, given its high bactericidal activity
      against S. aureus (including strains resistant to penicillin, methicillin,
      ampicillin, cloxacillin), S. epidermidis, Streptococcus pyogenes,
      Propionibacterium acnes, Corinebatteria, Clostridia. Additionally, FA presents a
      low risk of resistance even in methicillin-resistant S. aureus strains, a common
      pathogen implied in the etiology of skin infections and infected atopic eczema.
      Such feature makes FA particularly useful in the management of these medical
      conditions. Finally, possibly due to its large steric effect, FA has proved a
      very low risk of contact sensitization. Overall, data on FA efficacy, safety,
      sensitization potential, resistance profile and spectrum selectivity make it a
      first-choice option in the treatment of primary and secondary skin infection. 

PMID- 25068237
TI  - Primary umbilical endometriosis: description of a case.

PMID- 25068236
TI  - Medical, demographical and social aspects of syphilis: the case of infected sex
      workers in Greece during Interwar.
AB  - The aim of this research is to present syphilis among women described as
      "indecent" according to the records of the Venereal Diseases Hospital "Andreas
      Syggros", which is located in Athens, during the period 1931-1935. In
      impoverished Greece of the Interwar period, factors such as criminal ignorance,
      or lack of information on sexually transmitted diseases (STDs) along with
      inadequate health controls of sex workers, resulted in a dramatic spread of
      syphilis, whereas "Andreas Syggros" hospital accommodated thousands of patients.
      The inflow of 1.300.000 Greek refugees from Asia Minor, after the Greek defeat by
      the Turkish army in the war of 1922, resulted in a notable change in the
      demographics of the country, while the combination of miserable living
      conditions, unemployment, economic crisis of the Interwar period, political
      instability and dysfunction of the State led to an increased number of illegal
      sex workers and syphilis outbreaks. Despite the introduction of an ad hoc Act to
      control STDs since 1923, the State was unable to limit the transmissibility of
      syphilis and to control prostitution. Unfortunately, the value of this historical
      paradigm is borne out by a contemporary example, i.e. the scandal of HIV
      seropositive sex workers in -beset by economic crisis- Greece in May 2012. It
      turns out that ignorance, failure to comply with the law, change in the mentality
      of the citizens in an economically ruined society, and most notably dysfunction
      of public services during periods of crisis, are all risk factors for the spread
      of serious infectious diseases. 

PMID- 25068238
TI  - Cutaneous metastasis of colonic adenocarcinoma presenting as multiple agminated
      papules over the trunk and thighs.

PMID- 25068239
TI  - Multifocal perigenital cutaneous larva migrans.

PMID- 25068240
TI  - Polymorphous-like eruption of the heels.

PMID- 25068241
TI  - Salinity-induced accumulation of organic osmolytes in barley and wheat leaves
      correlates with increased oxidative stress tolerance: in planta evidence for
      cross-tolerance.
AB  - Salinity tolerance in plants is dependent on their abilities to adjust
      osmotically to reduced soil water potential and to keep intracellular ROS levels
      under control. Both these processes are believed to rely on de novo synthesis of
      organic osmolytes (traditionally defined as compatible solutes). However direct
      in planta evidence for anti-oxidant roles of compatible solutes are scarce. In
      this work, we induced changes in the level of endogenous organic osmolytes by
      exposing plants to various levels of NaCl (salinity stress; 50-300 mM range) and
      then studying sensitivity of leaves to oxidative (UV-B) stress. Increase in the
      external NaCl concentrations was accompanied by the progressive accumulation in
      leaf Na(+). This accumulation was much higher in old leaves compared with young
      ones. In old leaves, three major inorganic ions (Na(+), Cl(-) and K(+)) have made
      67.7% and 70.4% of leaf osmotic potential (in wheat and barley, respectively)
      when exposed to 200 mM NaCl treatment, while in young leaves their contribution
      was only 43.9% and 46.8%, respectively. Here, organic osmolytes played a
      substantial role in leaf osmotic adjustment. Increased accumulation of organic
      osmolytes correlated strongly with activity of PSII in leaves exposed to
      oxidation inducing UV-B treatment in both species (R(2) = 0.50 for wheat and 0.71
      for barley). We conclude that salinity-induced accumulation of organic osmolytes
      in barley and wheat leaves correlates with increased oxidative stress tolerance
      and provides the evidence for a mechanism of cross-tolerance between these two
      stresses. 

PMID- 25068243
TI  - Systemic gene silencing in plants triggered by fluorescent nanoparticle-delivered
      double-stranded RNA.
AB  - A cationic fluorescence nanoparticle efficiently enters plants with high
      transfection efficacy. Applying a mixture of G2/dsRNA to the model plant,
      Arabidopsis root, leads to significant reduction in the expression of important
      developmental genes and results in apparent phenotypes. This study reports a non
      viral gene nanocarrier which triggers gene silencing in plants and leads to
      systemic phenotypes. 

PMID- 25068244
TI  - Simultaneous degradation of cypermethrin and its metabolite, 3-phenoxybenzoic
      acid, by the cooperation of Bacillus licheniformis B-1 and sphingomonas sp. SC-1.
AB  - Cypermethrin (CY) and its metabolite, 3-phenoxybenzoic acid (3-PBA), generally
      coexist in agricultural soil and cause a toxic effect on the human body. In this
      study, CY and its metabolite 3-PBA were simultaneously degraded by the
      cooperation of Bacillus licheniformis B-1 and Sphingomonas sp. SC-1. The effects
      of the inoculation proportion and inoculation method of these two strains,
      cultivation time, and initial CY content on the degradation of CY and 3-PBA were
      investigated. Furthermore, the degradation of CY and 3-PBA in soil environment by
      using the cooperation of these two strains was also determined. When the
      inoculation proportion of the biomass of strain B-1/strain SC-1 was 3.3:6.7,
      strain B-1 was inoculated first, and strain SC-1 was inoculated after 24 h of
      cultivation, 75.60% CY (100 mg L(-1)) was degraded at 72 h and the 3-PBA content
      was 10.31 mg L(-1). Compared with those by using only strain B-1, the half-life
      of CY by using these two strains was shortened from 71.90 to 35.71 h, and the
      yield coefficient of 3-PBA was decreased from 0.8938 to 0.2651. As in the soil
      environment, the CY content by using these two strains within a period of 25 days
      declined from 22.71 to 5.33 mg kg(-1) and the 3-PBA content was 1.84 mg kg(-1).
      Compared with those by using only strain B-1, the half-life of CY by using these
      two strains was shortened from 19.86 to 11.34 days and the yield coefficient of 3
      PBA was decreased from 0.5302 to 0.2056. This work could develop a promising
      approach for the simultaneous degradation of CY and its metabolite 3-PBA in
      agricultural soil. 

PMID- 25068245
TI  - Health-related quality of life in pediatric cardiac extracorporeal life support
      survivors.
AB  - OBJECTIVE: To assess the health-related quality of life of children who received
      cardiac extracorporeal life support. We hypothesized that extracorporeal life
      support survivors have lower health-related quality-of-life scores when compared
      with a healthy sample, with children with chronic conditions, and with children
      who had surgery for congenital heart disease and did not receive extracorporeal
      life support. DESIGN: Prospective cohort study. SETTING: Stollery Children's
      Hospital and Complex Pediatric Therapies Follow-up Program clinics. PATIENTS:
      Children less than or 5 years old with diagnosis of cardiac disease (congenital
      or acquired) who received extracorporeal life support at the Stollery Children's
      Hospital from 1999 to 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Health-related quality of life was assessed using the PedsQL 4.0 Generic Core
      Scales completed by the children's parents at the time of follow-up. Forty-seven
      cardiac extracorporeal life support survivors had their health-related quality of
      life assessed at a median age of 4 years. Compared with a healthy sample,
      children who received venoarterial extracorporeal life support have significantly
      lower PedsQL (64.9 vs 82.2; p < 0.0001). The PedsQL scores of children who
      received extracorporeal life support were also significantly lower than those of
      children with chronic health conditions (64.9 vs 73.1; p = 0.007). Compared with
      children with congenital heart disease who underwent cardiac surgery early in
      infancy and who did not receive extracorporeal life support, extracorporeal life
      support survivors had significantly lower PedsQL scores (64.9 vs 81.1; p <
      0.0001). Multiple linear regression analysis found an independent association
      between both higher inotrope score in the first 24 hours of extracorporeal life
      support and longer hospital length of stay, with lower PedsQL scores.
      CONCLUSIONS: Pediatric cardiac extracorporeal life support survivors showed lower
      health-related quality of life than healthy children, children with chronic
      conditions, and children with congenital heart disease who did not receive
      extracorporeal life support.

PMID- 25068246
TI  - Reducing blood testing in pediatric patients after heart surgery: a quality
      improvement project.
AB  - OBJECTIVES: To safely optimize blood testing and costs for pediatric cardiac
      surgical patients without adversely impacting patient outcomes. DESIGN: This is a
      quality improvement cohort project with pre- and postintervention groups.
      SETTING: University-affiliated pediatric cardiac ICU in a tertiary care
      children's hospital. PATIENTS: All patients were surgical patients for whom Risk
      Adjustment for Congenital Heart Surgery categories allowed for stratification by
      complexity. The preintervention group was treated in 2010 and the
      postintervention group in 2011. INTERVENTIONS: Laboratory ordering processes were
      analyzed, and practice changed to limit standing blood test orders and requires
      individualized ordering. MEASUREMENTS AND MAIN RESULTS: Three hundred nineteen
      patients were studied in 2010 and 345 in 2011. Groups were similar in median age,
      weight, length of stay (ICU length of stay), and Risk Adjustment for Congenital
      Heart Surgery category. There was a reduction in the total blood tests per
      patient (24 vs 38; p < 0.0001) and length of stay adjusted tests per patient-day
      (10.4 vs 14.4; p = 0.0001) in the postintervention group. The largest test
      reductions were blood gases and single electrolytes. Adverse outcomes, such as
      extubation failure (6.4% vs 5.6%), central catheter-associated bloodstream
      infection (2.2 vs 1.5), and hospital mortality (0.6% vs 0.6%), were not
      significantly different between the groups. Cost analysis demonstrated an overall
      laboratory cost savings of 32%. In addition, the volume of packed RBC
      transfusions was also significantly decreased in the postintervention group among
      the most complex patients (Risk Adjustment for Congenital Heart Surgery, 6).
      CONCLUSIONS: Blood testing rates were safely decreased in postoperative pediatric
      cardiac patients by changing laboratory ordering practices. In addition, packed
      RBC transfusion was decreased among the most complex patients.

PMID- 25068247
TI  - Development of learning objectives and a validated testing tool for management of
      pediatric mechanical ventilation*.
AB  - OBJECTIVES: Graduate medical education is shifting toward an outcome-based
      paradigm, where physicians are evaluated for competency using well-defined
      criteria. Our aim was to learning objectives and a testing tool to assess
      competency in the management of mechanical ventilation for infants, children, and
      adolescents and to verify that the test was reliable and valid. DESIGN:
      Prospective reliability and validity study. SETTING: Large, university-affiliated
      academic hospital. SUBJECTS: Sixty-one total subjects from five different
      academic centers divided into three groups of varying experience. The groups were
      second- and third-year pediatric residents (Novice), second- and third-year
      pediatric critical care fellows (Advanced), and pediatric critical care faculty
      (Expert). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ten learning
      objectives considered important for the management of pediatric mechanical
      ventilation were developed from expert opinion and current evidence. Based on
      these objectives, a 35-question multiple choice, knowledge- and case-based test
      was created. Content validity was achieved by consensus of three experts in
      pediatric critical care medicine evaluating whether the questions reflected the
      learning objectives and the responses were consistent with current practice and
      evidence-based medicine. The test was then administered to the three groups to
      establish construct validity. The "Novice" group scored a mean of 34.6% (95% CI,
      28-41%), the "Advanced" group a mean of 59.4% (95% CI, 53-65%), and the "Expert"
      group a mean of 74.8% (95% CI, 69-80%), with p less than 0.01 for all
      comparisons. As determined by Hoyt's analysis, the reliability coefficient was
      0.89, reflecting excellent reliability. CONCLUSIONS: This is the first
      description of specific learning objectives for management of pediatric
      mechanical ventilation and the first validated and reliable testing tool for
      assessing knowledge. This tool could be used by fellowship programs to assess
      fellow competency and identify knowledge gaps in this area prior to completion of
      training. Further work must be done to determine the criteria for determination
      of competency.

PMID- 25068248
TI  - Respiratory secretion analyses in the evaluation of ventilator-associated
      pneumonia: a survey of current practice in pediatric critical care.
AB  - OBJECTIVE: Ventilator-associated pneumonia is among the most common nosocomial
      infections in the PICU. Respiratory secretion cultures and Gram stains are
      frequently obtained for diagnosis and to guide therapy, but their specificity is
      questionable. We conducted a scenario-based survey of pediatric intensivists to
      assess their antibiotic use in response to hypothetical tracheal aspirate culture
      and Gram stain results. DESIGN: Scenario-based survey. SETTING: A hypothetical
      PICU. PATIENTS: Three hypothetical scenarios of intubated children with fever and
      leukocytosis: a 4-month-old child with respiratory syncytial virus infection; a 7
      year-old child with acute respiratory distress syndrome; and a 10-year-old child
      with aspiration pneumonia. INTERVENTIONS: Scenario-based survey of pediatric
      intensivists from the Pediatric Acute Lung Injury and Sepsis Network.
      MEASUREMENTS AND MAIN RESULTS: Ninety-four percent of the pediatric intensivists
      surveyed would obtain a respiratory secretion culture and Gram stain in the
      evaluation of an intubated child with fever and leukocytosis, most by simple
      tracheal aspiration but a minority (32%) by bronchoalveolar lavage. "Bacterial
      pathogenicity" was considered the most important result of the analysis. Although
      there were some differences across the three scenarios, most would initiate
      antibiotics if culture results identified methicillin-sensitive or methicillin
      resistant Staphylococcus aureus or Pseudomonas and, on average, continue
      antibiotics for 7-10 days. CONCLUSIONS: The majority of pediatric intensivists
      would obtain respiratory secretion cultures and Gram stains in the evaluation of
      an intubated child with fever and leukocytosis and initiate antibiotics guided by
      the results. The specificity of respiratory secretion cultures and Gram stains
      for the diagnosis of ventilator-associated pneumonia requires critical evaluation
      as this diagnosis is responsible for more than half of antibiotic use in the
      PICU.

PMID- 25068249
TI  - Long-term dexmedetomidine use and safety profile among critically ill children
      and neonates.
AB  - OBJECTIVE: To determine whether long-term dexmedetomidine dosing is associated
      with lower opioid and benzodiazepine use without risk of significant hemodynamic
      changes and/or withdrawal. DESIGN: Retrospective, observational study. SETTING:
      PICU, cardiovascular ICU, and neonatal ICU in a single, tertiary care, academic
      children's hospital. SUBJECTS: We included all patients less than or equal to 21
      years old, who received dexmedetomidine for greater than or equal to 72 hours
      from December 2008 to December 2010 resulting in a 98-subject cohort.
      INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The median duration of
      dexmedetomidine use was 141 hours. A decrease in systolic blood pressure and
      heart rate was seen after initiation of dexmedetomidine. After dexmedetomidine
      was discontinued, systolic blood pressure was statistically significantly higher
      than baseline. Similarly, heart rate showed a significant increase from baseline
      following discontinuation of dexmedetomidine. Starting dexmedetomidine was not
      associated with a significant difference in the dosing of opiates or
      benzodiazepines. Comfort scores were significantly lower at 2 and 72 hours of
      dexmedetomidine infusion. After stopping dexmedetomidine, the comfort score for
      patients at 1 hour was statistically higher than for patients at cessation of the
      infusion. Thirty percent of patients who were taken off dexmedetomidine, whether
      weaned or abruptly stopped, had withdrawal symptoms and scores recorded with
      agitation, tremor, and decreased sleep being most prominent. CONCLUSIONS:
      Hemodynamic effects of dexmedetomidine did not limit long-term use in this
      diverse population. After the addition of dexmedetomidine, opioid and
      benzodiazepine doses did not significantly escalate, and patients were more
      comfortable as evidenced by decreasing comfort scores. Withdrawal from
      dexmedetomidine may be an issue and manifests as agitation, tremors, and
      decreased sleep.

PMID- 25068250
TI  - Prevalence of burnout in pediatric intensivists: an observational comparison with
      general pediatricians.
AB  - OBJECTIVE: To study the prevalence of burnout in general pediatricians and
      pediatric intensivists and to evaluate factors that may be associated with this
      syndrome. DESIGN: Observational cohort study. SETTING: Pediatric departments of
      two hospitals in south Brazil. PATIENTS: Pediatric intensivists working in two
      regional PICUs and general pediatricians working in the outpatient departments in
      the same hospitals. INTERVENTION: Two researchers, blinded to the workplace of
      the physicians, undertook the assessment of burnout using the Maslach Burnout
      Inventory scale. Burnout was defined as high score in the domains for "emotional
      exhaustion" or "depersonalization" or a low score in the "professional
      accomplishment" domain. MEASUREMENTS AND MAIN RESULTS: The PICU and general
      pediatrician groups were similar demographically, and each had 35 recruits.
      Burnout was present in 50% of the study recruits and was more frequent among
      pediatric intensivists than general pediatricians (71% vs 29%, respectively, p <
      0.01). In regard to the individual Maslach Burnout Inventory domains, the average
      score was higher for emotional exhaustion and depersonalization and lower for
      professional accomplishment in the PICU group (p < 0.01). A cluster analysis
      showed that pediatric intensivists were more likely to develop the burnout
      syndrome involving all Maslach Burnout Inventory domains. The multivariate
      analysis found that the odds ratio for burnout in pediatric intensivists was 5.7
      (95% CI, 1.9-16.7; p < 0.01). CONCLUSIONS: Burnout is frequent among pediatric
      intensivists and characterized by cumulative involvement of emotional exhaustion,
      depersonalization, and professional accomplishment. Earlier recognition of
      emotional exhaustion may be important in preventing the development of a complete
      burnout syndrome. Improvement in workplace characteristics and measures to
      improve physician resilience are entirely warranted.

PMID- 25068251
TI  - Use of therapeutic plasma exchange in children with thrombocytopenia-associated
      multiple organ failure in the Turkish thrombocytopenia-associated multiple organ
      failure network.
AB  - OBJECTIVE: Thrombocytopenia-associated multiple organ failure can lead to high
      mortality in critically ill children, possibly related to consequences of
      thrombotic microangiopathy. Plasma exchange therapy may improve thrombotic
      microangiopathy. The purpose of this observational cohort study is to describe
      whether there is an association between use of plasma exchange therapy and
      outcome in the Turkish thrombocytopenia-associated multiple organ failure
      network. SETTING-INTERVENTIONS: We performed a retrospective cohort analysis in
      patients with thrombocytopenia-associated multiple organ failure at three
      different PICUs comparing those who received plasma exchange (+) plus standard
      therapies with those who did not receive plasma exchange (-) and only received
      standard therapies. RESULTS: Among 42 of the enrolled patients with
      thrombocytopenia-associated multiple organ failure, all had a primary or
      secondary sepsis diagnosis. Fifteen received plasma exchange therapy (PE [+]
      group) and 27 received standard medical treatment without plasma exchange (PE [-]
      group). The mean age was 17.69 months (8.24-54.22) in the PE (+) group and 13.46
      months (6.47-20.55) in the PE (-) group. Age (p = 0.232), gender (p = 0.206),
      thrombocyte count (p = 0.09), Organ Failure Index score (p = 0.111), and
      pediatric logistic organ dysfunction score (p = 0.177) at admission were not
      statistically different between groups. The overall 28-day mortality was higher
      in the PE (-) group (70.37%) compared with the PE (+) group (26.67%) (univariate
      p = 0.006; multivariate controlling for pediatric logistic organ dysfunction,
      Organ Failure Index, Pediatric Risk of Mortality scores, and neurological failure
      p = 0.048). Length of stay was increased in the PE (+) group (p = 0.004).
      CONCLUSIONS: The positive association found between use of plasma exchange
      therapy and improved survival supports the potential of this therapy in Turkish
      children with thrombocytopenia-associated multiple organ failure. The positive,
      although less so, associated treatment effect observed after controlling for
      illness severity provides further rationale for performing a randomized
      controlled trial in the pediatric Turkish thrombocytopenia-associated multiple
      organ failure network. Sample size calculations call for a 100-patient trial with
      a pre hoc interim analysis after enrollment of 50 patients with thrombocytopenia
      associated multiple organ failure.

PMID- 25068252
TI  - Clinical course and outcome predictors of critically ill infants with complete
      DiGeorge anomaly following thymus transplantation.
AB  - OBJECTIVES: To identify risk factors for PICU admission and mortality of infants
      with complete DiGeorge anomaly treated with thymus transplantation. We
      hypothesized that age at transplantation and the presence of congenital heart
      disease would be risk factors for emergent PICU admission, and these factors plus
      development of septicemia would increase morbidity and mortality. DESIGN:
      Retrospective review. SETTING: Academic medical-surgical PICU. PATIENTS: All
      infants with complete DiGeorge anomaly treated with thymus transplantation
      between January 1, 1993, and July 1, 2010. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Consent was obtained from 71 infants with complete DiGeorge anomaly
      for thymus transplantation, and 59 infants were transplanted. Median age at
      transplantation was 5.0 months (range, 1.1-22.1 mo). After transplantation, 12 of
      59 infants (20%) required 25 emergent PICU admissions. Seven of 12 infants (58%)
      survived to PICU discharge with six surviving 6 months posttransplantation. Forty
      two of 59 infants (71%) transplanted had congenital heart disease, and 9 of 12
      (75%) who were admitted to the PICU had congenital heart disease. In 15 of 25
      admissions (60%), intubation and mechanical ventilation were necessary. There was
      no difference between median ventilation-free days between infants with and
      without congenital heart disease (33 d vs 23 d, p = 0.544). There was also no
      correlation between ventilation-free days and age of transplantation (R, 0.17; p
      = 0.423). Age at transplantation and the presence of congenital heart disease
      were not associated with risk for PICU admission (odds ratio, 0.95; 95% CI, 0.78
      1.15 and odds ratio, 1.27; 95% CI, 0.30-5.49, respectively) or PICU mortality
      (odds ratio, 0.98; 95% CI, 0.73-1.31 and odds ratio, 0.40; 95% CI, 0.15-1.07,
      respectively). CONCLUSIONS: Most transplanted infants did not require emergent
      PICU admission. Age at transplantation and the presence of congenital heart
      disease were not associated with PICU admission or mortality.

PMID- 25068253
TI  - Abdominal near-infrared spectroscopy measurements are lower in preterm infants at
      risk for necrotizing enterocolitis.
AB  - OBJECTIVE: Near-infrared spectroscopy is a noninvasive method of measuring local
      tissue oxygenation (StO2). Abdominal StO2 measurements in preterm piglets are
      directly correlated with changes in intestinal blood flow and markedly reduced by
      necrotizing enterocolitis. The objectives of this study were to use near-infrared
      spectroscopy to establish normal values for abdominal StO2 in preterm infants and
      test whether these values are reduced in infants who develop necrotizing
      enterocolitis. DESIGN: We conducted a 2-year prospective cohort study where we
      prospectively measured abdominal StO2 in preterm infants, to establish reference
      values for preterm infants, and compared the near-infrared spectroscopy values
      with preterm infants in the cohort that developed necrotizing enterocolitis.
      SETTING: Two neonatal ICUs: one at Texas Children's Hospital and the other at Ben
      Taub General Hospital in Houston, TX. PATIENTS: We enrolled 100 preterm infants
      (< 32 weeks' gestation and < 1,500 g birth weight) between January 2007 and
      November 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight neonates
      with incomplete data were excluded. Mean abdominal StO2 in normal preterm infants
      (n = 78) during the first week of life was significantly higher than in those who
      later developed necrotizing enterocolitis (n = 14) (77.3% +/- 14.4% vs 70.7% +/-
      19.1%, respectively, p = 0.002). An StO2 less than or equal to 56% identified
      preterm infants progressing to necrotizing enterocolitis with 86% sensitivity,
      64% specificity, 96% negative predictive value, and 30% positive predictive
      value. Using logistic regression, StO2 less than or equal to 56% was
      independently associated with a significantly increased risk of necrotizing
      enterocolitis (odds ratio, 14.1; p = 0.01). Furthermore, infants with necrotizing
      enterocolitis demonstrated significantly more variation in StO2 both during and
      after feeding in the first 2 weeks of life. CONCLUSIONS: This study establishes
      normal values for abdominal StO2 in preterm infants and demonstrates decreased
      values and increased variability in those with necrotizing enterocolitis.
      Abdominal near-infrared spectroscopy monitoring of preterm infants may be a
      useful tool for early diagnosis and guiding treatment of necrotizing
      enterocolitis.

PMID- 25068256
TI  - A plant chamber system with downstream reaction chamber to study the effects of
      pollution on biogenic emissions.
AB  - A system of two plant chambers and a downstream reaction chamber has been set up
      to investigate the emission of biogenic volatile organic compounds (BVOCs) and
      possible effects of pollutants such as ozone. The system can be used to compare
      BVOC emissions from two sets of differently treated plants, or to study the
      photochemistry of real plant emissions under polluted conditions without exposing
      the plants to pollutants. The main analytical tool is a proton-transfer-reaction
      time-of-flight mass spectrometer (PTR-TOF-MS) which allows online monitoring of
      biogenic emissions and chemical degradation products. The identification of BVOCs
      and their oxidation products is aided by cryogenic trapping and subsequent in
      situ gas chromatographic analysis. 

PMID- 25068254
TI  - Plant cells use auxin efflux to explore geometry.
AB  - Cell movement is the central mechanism for animal morphogenesis. Plant cell
      development rather relies on flexible alignment of cell axis adjusting cellular
      differentiation to directional cues. As central input, vectorial fields of
      mechanical stress and gradients of the phytohormone auxin have been discussed. In
      tissue contexts, mechanical and chemical signals will always act in concert;
      experimentally it is difficult to dissect their individual roles. We have
      designed a novel approach, based on cells, where directionality has been
      eliminated by removal of the cell wall. We impose a new axis using a microfluidic
      set-up to generate auxin gradients. Rectangular microvessels are integrated
      orthogonally with the gradient. Cells in these microvessels align their new axis
      with microvessel geometry before touching the wall. Auxin efflux is necessary for
      this touch-independent geometry exploration and we suggest a model, where auxin
      gradients can be used to align cell axis in tissues with minimized mechanical
      tensions. 

PMID- 25068257
TI  - Accumulating research: a systematic account of how cumulative meta-analyses would
      have provided knowledge, improved health, reduced harm and saved resources.
AB  - BACKGROUND: "Cumulative meta-analysis" describes a statistical procedure to
      calculate, retrospectively, summary estimates from the results of similar trials
      every time the results of a further trial in the series had become available. In
      the early 1990 s, comparisons of cumulative meta-analyses of treatments for
      myocardial infarction with advice promulgated through medical textbooks showed
      that research had continued long after robust estimates of treatment effects had
      accumulated, and that medical textbooks had overlooked strong, existing evidence
      from trials. Cumulative meta-analyses have subsequently been used to assess what
      could have been known had new studies been informed by systematic reviews of
      relevant existing evidence and how waste might have been reduced. METHODS AND
      FINDINGS: We used a systematic approach to identify and summarise the findings of
      cumulative meta-analyses of studies of the effects of clinical interventions,
      published from 1992 to 2012. Searches were done of PubMed, MEDLINE, EMBASE, the
      Cochrane Methodology Register and Science Citation Index. A total of 50 eligible
      reports were identified, including more than 1,500 cumulative meta-analyses. A
      variety of themes are illustrated with specific examples. The studies showed that
      initially positive results became null or negative in meta-analyses as more
      trials were done; that early null or negative results were over-turned; that
      stable results (beneficial, harmful and neutral) would have been seen had a meta
      analysis been done before the new trial; and that additional trials had been much
      too small to resolve the remaining uncertainties. CONCLUSIONS: This large, unique
      collection of cumulative meta-analyses highlights how a review of the existing
      evidence might have helped researchers, practitioners, patients and funders make
      more informed decisions and choices about new trials over decades of research.
      This would have led to earlier uptake of effective interventions in practice,
      less exposure of trial participants to less effective treatments, and reduced
      waste resulting from unjustified research.

PMID- 25068258
TI  - An accelerometry-based methodology for assessment of real-world bilateral upper
      extremity activity.
AB  - BACKGROUND: The use of both upper extremities (UE) is necessary for the
      completion of many everyday tasks. Few clinical assessments measure the abilities
      of the UEs to work together; rather, they assess unilateral function and compare
      it between affected and unaffected UEs. Furthermore, clinical assessments are
      unable to measure function that occurs in the real-world, outside the clinic.
      This study examines the validity of an innovative approach to assess real-world
      bilateral UE activity using accelerometry. METHODS: Seventy-four neurologically
      intact adults completed ten tasks (donning/doffing shoes, grooming, stacking
      boxes, cutting playdough, folding towels, writing, unilateral sorting, bilateral
      sorting, unilateral typing, and bilateral typing) while wearing accelerometers on
      both wrists. Two variables, the Bilateral Magnitude and Magnitude Ratio, were
      derived from accelerometry data to distinguish between high- and low-intensity
      tasks, and between bilateral and unilateral tasks. Estimated energy expenditure
      and time spent in simultaneous UE activity for each task were also calculated.
      RESULTS: The Bilateral Magnitude distinguished between high- and low-intensity
      tasks, and the Magnitude Ratio distinguished between unilateral and bilateral UE
      tasks. The Bilateral Magnitude was strongly correlated with estimated energy
      expenditure (rho = 0.74, p<0.02), and the Magnitude Ratio was strongly correlated
      with time spent in simultaneous UE activity (rho = 0.93, p<0.01) across tasks.
      CONCLUSIONS: These results demonstrate face validity and construct validity of
      this methodology to quantify bilateral UE activity during the performance of
      everyday tasks performed in a laboratory setting, and can now be used to assess
      bilateral UE activity in real-world environments.

PMID- 25068259
TI  - Muramyl dipeptide: Not just another brick in the wall.
AB  - The robust expression of microbial pattern recognition receptors such as TLR4 and
      Nod2 in intestinal stem cells reflects an active communication dynamic between
      the host and the gut microbiota. A new study reveals that muramyl dipeptide, the
      bacterial cell wall peptidoglycan motif, activates Nod2 within crypt base
      columnar Lgr5-positive stem cells and promotes their survival. Apart from the
      immediate relevance to the growth of organoids for in vitro experiments, the
      study raises new questions about the molecular mechanisms whereby gut microbes
      influence intestinal physiology. 

PMID- 25068260
TI  - New insight on biological interaction analysis: new nanocrystalline mixed metal
      oxide SPME fiber for GC-FID analysis of BTEX and its application in human
      hemoglobin-benzene interaction studies.
AB  - Nanocrystalline mixed metal oxides (MMO) of various metal cations were
      synthesized and were used for coating a piece of copper wire as a new high
      sensitive solid phase micro extraction (SPME) fiber in extraction and
      determination of BTEX compounds from the headspace of aqueous samples prior to GC
      FID analysis. Under optimum extraction conditions, the proposed fiber exhibited
      low detection limits, and quantification limits, good reproducibility, simple and
      fast preparation method, high fiber capacity and high thermal and mechanical
      durability. These are some of the most important advantages of the new fiber. The
      proposed fiber was used for human hemoglobin upon interaction with benzene.
      Binding isotherm, Scatchard and Klotz logarithmic plots were constructed using HS
      SPME-GC data, accurately. The obtained binding isotherm analyzed using Hill
      method. The Hill parameters have been obtained by calculating saturation
      parameter from the ratio of measured chromatographic peak areas in the presence
      and absence of hemoglobin. In this interaction, Hill coefficient and Hill
      constant determined as (nH = 6.14 and log KH = 6.47) respectively. These results
      reveal the cooperativity of hemoglobin upon interaction with benzene.

PMID- 25068261
TI  - Mynodbcsv: lightweight zero-config database solution for handling very large CSV
      files.
AB  - Volumes of data used in science and industry are growing rapidly. When
      researchers face the challenge of analyzing them, their format is often the first
      obstacle. Lack of standardized ways of exploring different data layouts requires
      an effort each time to solve the problem from scratch. Possibility to access data
      in a rich, uniform manner, e.g. using Structured Query Language (SQL) would offer
      expressiveness and user-friendliness. Comma-separated values (CSV) are one of the
      most common data storage formats. Despite its simplicity, with growing file size
      handling it becomes non-trivial. Importing CSVs into existing databases is time
      consuming and troublesome, or even impossible if its horizontal dimension reaches
      thousands of columns. Most databases are optimized for handling large number of
      rows rather than columns, therefore, performance for datasets with non-typical
      layouts is often unacceptable. Other challenges include schema creation, updates
      and repeated data imports. To address the above-mentioned problems, I present a
      system for accessing very large CSV-based datasets by means of SQL. It's
      characterized by: "no copy" approach--data stay mostly in the CSV files; "zero
      configuration"--no need to specify database schema; written in C++, with boost
      [1], SQLite [2] and Qt [3], doesn't require installation and has very small size;
      query rewriting, dynamic creation of indices for appropriate columns and static
      data retrieval directly from CSV files ensure efficient plan execution;
      effortless support for millions of columns; due to per-value typing, using mixed
      text/numbers data is easy; very simple network protocol provides efficient
      interface for MATLAB and reduces implementation time for other languages. The
      software is available as freeware along with educational videos on its website
      [4]. It doesn't need any prerequisites to run, as all of the libraries are
      included in the distribution package. I test it against existing database
      solutions using a battery of benchmarks and discuss the results.

PMID- 25068263
TI  - Recombinant scorpine produced using SUMO fusion partner in Escherichia coli has
      the activities against clinically isolated bacteria and inhibits the Plasmodium
      falciparum parasitemia in vitro.
AB  - Scorpine, a small cationic peptide from the venom of Pandinus imperator, which
      has been shown to have anti-bacterial and anti-plasmodial activities, has
      potential important applications in the pharmaceutical industries. However, the
      isolation of scorpine from natural sources is inefficient and time-consuming.
      Here, we first report the expression and purification of recombinant scorpine in
      Escherichia coli, using small ubiquitin-related modifier (SUMO) fusion partner.
      The fusion protein was expressed in soluble form in E. coli, and expression was
      verified by SDS-PAGE and western blotting analysis. The fusion protein was
      purified to 90% purity by nickel-nitrilotriacetic acid (Ni2+-NTA) resin
      chromatography. After the SUMO-scorpine fusion protein was cleaved by the SUMO
      protease, the cleaved sample was reapplied to a Ni2+-NTA column. Tricine/SDS-PAGE
      gel results indicated that Scorpine had been purified successfully to more than
      95% purity. The recombinantly expressed Scorpine showed anti-bacterial activity
      against two standard bacteria including Staphylococcus aureus ATCC 29213 and
      Acinetobacter baumannii ATCC 19606, and clinically isolated bacteria including S.
      aureus S, S. aureus R, A. baumannii S, and A. baumannii R. It also produced 100%
      reduction in Plasmodium falciparum parasitemia in vitro. Thus, the expression
      strategy presented in this study allowed convenient high yield and easy
      purification of recombinant Scorpine for pharmaceutical applications in the
      future. 

PMID- 25068264
TI  - Association of soluble HLA-G with acute rejection episodes and early development
      of bronchiolitis obliterans in lung transplantation.
AB  - Lung transplantation has evolved into a life-saving therapy for select patients
      with end-stage lung diseases. However, long-term survival remains limited because
      of bronchiolitis obliterans syndrome (BOS). Soluble HLA-G, a mediator of adaptive
      immunity that modulates regulatory T cells and certain classes of effector T
      cells, may be a useful marker of survival free of BOS. We conducted a
      retrospective, single-center, pilot review of 38 lung transplant recipients who
      underwent collection of serum and bronchoalveolar lavage fluid 3, 6 and 12 months
      after transplantation, and compared soluble HLA-G concentrations in each to the
      presence of type A rejection and lymphocytic bronchiolitis in the first 12 months
      and to the presence of BOS at 24 months after transplantation. Lung soluble HLA-G
      concentrations were directly related to the presence of type A rejection but not
      to lymphocytic bronchiolitis. Our data demonstrate that soluble HLA-G
      concentrations in bronchoalveolar lavage but not in serum correlates with the
      number of acute rejection episodes in the first 12 months after lung
      transplantation, and thus may be a reactive marker of rejection. 

PMID- 25068265
TI  - The health effects of a forest environment on subclinical cardiovascular disease
      and heath-related quality of life.
AB  - BACKGROUND: Assessment of health effects of a forest environment is an important
      emerging area of public health and environmental sciences. PURPOSE: To
      demonstrate the long-term health effects of living in a forest environment on
      subclinical cardiovascular diseases (CVDs) and health-related quality of life
      (HRQOL) compared with that in an urban environment. MATERIALS AND METHODS: This
      study included the detailed health examination and questionnaire assessment of
      107 forest staff members (FSM) and 114 urban staff members (USM) to investigate
      the long-term health effects of a forest environment. Air quality monitoring
      between the forest and urban environments was compared. In addition, work-related
      factors and HRQOL were evaluated. RESULTS: Levels of total cholesterol, low
      density lipoprotein cholesterol, and fasting glucose in the USM group were
      significantly higher than those in the FSM group. Furthermore, a significantly
      higher intima-media thickness of the internal carotid artery was found in the USM
      group compared with that in the FSM group. Concentrations of air pollutants, such
      as NO, NO2, NOx, SO2, CO, PM2.5, and PM10 in the forest environment were
      significantly lower compared with those in the outdoor urban environment. Working
      hours were longer in the FSM group; however, the work stress evaluation as
      assessed by the job content questionnaire revealed no significant differences
      between FSM and USM. HRQOL evaluated by the World Health Organization Quality of
      Life-BREF questionnaire showed FSM had better HRQOL scores in the physical health
      domain. CONCLUSIONS: This study provides evidence of the potential beneficial
      effects of forest environments on CVDs and HRQOL.

PMID- 25068266
TI  - Fractures and mortality in relation to different osteoporosis treatments.
AB  - OBJECTIVES: Few studies have assessed the effectiveness of different drugs for
      osteoporosis (OP). We aimed to determine if fracture and mortality rates vary
      among patients initiating different OP medications. METHODS: We used the Medicare
      5% sample to identify new users of intravenous (IV) zoledronic acid (n=1.674),
      oral bisphosphonates (n=32.626), IV ibandronate (n=492), calcitonin (n=2.606),
      raloxifene (n=1.950), or parathyroid hormone (n=549). We included beneficiaries
      who were >=65 years of age, were continuously enrolled in fee-for-service
      Medicare and initiated therapy during 2007-2009. Outcomes were hip fracture,
      clinical vertebral fracture, and all-cause mortality, identified using inpatient
      and physician diagnosis codes for fracture, procedure codes for fracture repair,
      and vital status information. Cox regression models compared users of each
      medication to users of IV zoledronic acid, adjusting for multiple confounders.
      RESULTS: During follow-up (median, 0.8-1.5 years depending on the drug), 787
      subjects had hip fractures, 986 had clinical vertebral fractures, and 2.999 died.
      Positive associations included IV ibandronate with hip fracture (adjusted hazard
      ratio (HR), 2.37; 95% confidence interval (CI) 1.25-4.51), calcitonin with
      vertebral fracture (HR=1.59, 95%CI 1.04-2.43), and calcitonin with mortality
      (HR=1.31; 95%CI 1.02-1.68). Adjusted HRs for other drug-outcome comparisons were
      not statistically significant. CONCLUSIONS: IV ibandronate and calcitonin were
      associated with higher rates of some types of fracture when compared to IV
      zolendronic acid. The relatively high mortality associated with use of calcitonin
      may reflect the poorer health of users of this agent.

PMID- 25068267
TI  - Rapid identification of carbapenemase genes in gram-negative bacteria with an
      oligonucleotide microarray-based assay.
AB  - Rapid molecular identification of carbapenemase genes in Gram-negative bacteria
      is crucial for infection control and prevention, surveillance and for
      epidemiological purposes. Furthermore, it may have a significant impact upon
      determining the appropriate initial treatment and greatly benefit for critically
      ill patients. A novel oligonucleotide microarray-based assay was developed to
      simultaneously detect genes encoding clinically important carbapenemases as well
      as selected extended (ESBL) and narrow spectrum (NSBL) beta-lactamases directly
      from clonal culture material within few hours. Additionally, a panel of species
      specific markers was included to identify Escherichia coli, Pseudomonas
      aeruginosa, Citrobacter freundii/braakii, Klebsiella pneumoniae and Acinetobacter
      baumannii. The assay was tested using a panel of 117 isolates collected from
      urinary, blood and stool samples. For these isolates, phenotypic identifications
      and susceptibility tests were available. An independent detection of
      carbapenemase, ESBL and NSBL genes was carried out by various external reference
      laboratories using PCR methods. In direct comparison, the microarray correctly
      identified 98.2% of the covered carbapenemase genes. This included blaVIM (13 out
      of 13), blaGIM (2/2), blaKPC (27/27), blaNDM (5/5), blaIMP-2/4/7/8/13/14/15/16/31
      (10/10), blaOXA-23 (12/13), blaOXA-40-group (7/7), blaOXA-48-group (32/33),
      blaOXA-51 (1/1) and blaOXA-58 (1/1). Furthermore, the test correctly identified
      additional beta-lactamases [blaOXA-1 (16/16), blaOXA-2 (4/4), blaOXA-9 (33/33),
      OXA-10 (3/3), blaOXA-51 (25/25), blaOXA-58 (2/2), CTX-M1/M15 (17/17) and blaVIM
      (1/1)]. In direct comparison to phenotypical identification obtained by VITEK or
      MALDI-TOF systems, 114 of 117 (97.4%) isolates, including Acinetobacter baumannii
      (28/28), Enterobacter spec. (5/5), Escherichia coli (4/4), Klebsiella pneumoniae
      (62/63), Klebsiella oxytoca (0/2), Pseudomonas aeruginosa (12/12), Citrobacter
      freundii (1/1) and Citrobacter braakii (2/2), were correctly identified by a
      panel of species specific probes. This assay might be easily extended, adapted
      and transferred to point of care platforms enabling fast surveillance, rapid
      detection and appropriate early treatment of infections caused by multiresistant
      Gram-negative bacteria. 

PMID- 25068269
TI  - The association of thyroid nodule with non-iodized salt among Chinese children.
AB  - OBJECTIVE: The controversy that iodized salt may increase the risk of thyroid
      disorders has been aroused in China during the past decade. Most of studies
      focused on adult rather than children. We aimed to explore whether iodized salt
      was associated with an increased risk of thyroid nodule in Chinese children.
      METHODS: The cross-sectional study was conducted in Hangzhou, China, in 2010.
      Iodized salt intake, urine iodine concentration (UIC) and thyroid nodule (by
      ultrasonography) were measured in 3026 children. The associations of iodized salt
      with thyroid nodule were evaluated using multiple logistic regression models.
      RESULTS: The prevalence of thyroid nodule was 10.59% among Chinese children.
      Girls (11.89%) had higher prevalence of thyroid nodule than boys (9.26%). No
      significant association was observed between type of salt and thyroid nodule in
      pooled samples, boys and girls, respectively. Similar associations were observed
      between UIC and thyroid nodule. There was no significant association between milk
      consumption and thyroid nodule as well. CONCLUSION: The present study indicated
      that non-iodized salt may not increase the risk of thyroid nodules among Chinese
      children. Similar associations were observed between milk consumption, UIC and
      thyroid nodules.

PMID- 25068270
TI  - Autophagy-preferential degradation of MIR224 participates in hepatocellular
      carcinoma tumorigenesis.
AB  - Autophagy and microRNA (miRNA) are important regulators during cancer cell
      tumorigenesis. Impaired autophagy and high expression of the oncogenic microRNA
      MIR224 are prevalent in hepatocellular carcinoma (HCC); however, the relationship
      between the 2 phenomena remains elusive. In this study, we are the first to
      reveal that autophagy selectively regulates MIR224 expression through an
      autophagosome-mediated degradation system. Based on this finding, we further
      demonstrated that in hepatitis B virus (HBV)-related HCC, aberrant autophagy (low
      autophagic activity) results in accumulation of MIR224 and decreased expression
      of the target gene Smad4, which leads to increased cell migration and tumor
      formation. Preferential recruitment of MIR224 into the autophagosome was clearly
      demonstrated by a) miRNA in situ hybridization under confocal microscopy, and b)
      immunogold labeling of MIR224 under electron microscopy compared with a
      ubiquitously expressed microRNA MIRlet7e/let-7. Furthermore, we found that off
      label use of amiodarone, an antiarrhythmic agent, effectively suppressed HCC
      tumorigenesis through autophagy-mediated MIR224 degradation both in vitro and in
      vivo. In summary, we identified amiodarone as a new autophagy inducer, which may
      provide an alternative approach in HCC therapy through a novel tumor suppression
      mechanism. 

PMID- 25068268
TI  - Genome evolution in trypanosomatid parasites.
AB  - A decade of genome sequencing has transformed our understanding of how
      trypanosomatid parasites have evolved and provided fresh impetus to explaining
      the origins of parasitism in the Kinetoplastida. In this review, I will consider
      the many ways in which genome sequences have influenced our view of genomic
      reduction in trypanosomatids; how species-specific genes, and the genomic domains
      they occupy, have illuminated the innovations in trypanosomatid genomes; and how
      comparative genomics has exposed the molecular mechanisms responsible for
      innovation and adaptation to a parasitic lifestyle.

PMID- 25068271
TI  - Urbanization breaks up host-parasite interactions: a case study on parasite
      community ecology of rufous-bellied thrushes (Turdus rufiventris) along a rural
      urban gradient.
AB  - Urbanization drastically alters natural ecosystems and the structure of their
      plant and animal communities. Whereas some species cope successfully with these
      environmental changes, others may go extinct. In the case of parasite
      communities, the expansion of urban areas has a critical effect by changing the
      availability of suitable substrates for the eggs or free-larval stages of those
      species with direct life cycles or for the range of hosts of those species with
      complex cycles. In this study we investigated the influence of the degree of
      urbanization and environmental heterogeneity on helminth richness, abundance and
      community structure of rufous-bellied thrushes (Turdus rufiventris) along a rural
      urban gradient in the metropolitan region of Porto Alegre, State of Rio Grande do
      Sul, Brazil. This common native bird species of southern Brazil hosts 15
      endoparasite species at the study region. A total of 144 thrushes were collected
      with mist nets at 11 sites. The degree of urbanization and environmental
      heterogeneity were estimated by quantifying five landscape elements: buildings,
      woodlands, fields, bare lands, and water. Landscape analyses were performed at
      two spatial scales (10 and 100 ha) taking into account home range size and the
      potential dispersal distance of thrushes and their prey (intermediate hosts).
      Mean parasite richness showed an inverse relationship with the degree of
      urbanization, but a positive relationship with environmental heterogeneity.
      Changes in the structure of component communities along the rural-urban gradient
      resulted from responses to the availability of particular landscape elements that
      are compatible with the parasites' life cycles. We found that the replacement of
      natural environments with buildings breaks up host-parasite interactions, whereas
      a higher environmental (substrate) diversity allows the survival of a wider range
      of intermediate hosts and vectors and their associated parasites. 

PMID- 25068272
TI  - Evidence for chromatin-remodeling complex PBAP-controlled maintenance of the
      Drosophila ovarian germline stem cells.
AB  - In the Drosophila oogenesis, germline stem cells (GSCs) continuously self-renew
      and differentiate into daughter cells for consecutive germline lineage
      commitment. This developmental process has become an in vivo working platform for
      studying adult stem cell fate regulation. An increasing number of studies have
      shown that while concerted actions of extrinsic signals from the niche and
      intrinsic regulatory machineries control GSC self-renewal and germline
      differentiation, epigenetic regulation is implicated in the process. Here, we
      report that Brahma (Brm), the ATPase subunit of the Drosophila SWI/SNF chromatin
      remodeling complexes, is required for maintaining GSC fate. Removal or knockdown
      of Brm function in either germline or niche cells causes a GSC loss, but does not
      disrupt normal germline differentiation within the germarium evidenced at the
      molecular and morphological levels. There are two Drosophila SWI/SNF complexes:
      the Brm-associated protein (BAP) complex and the polybromo-containing BAP (PBAP)
      complex. More genetic studies reveal that mutations in polybromo/bap180, rather
      than gene encoding Osa, the BAP complex-specific subunit, elicit a defect in GSC
      maintenance reminiscent of the brm mutant phenotype. Further genetic interaction
      test suggests a functional association between brm and polybromo in controlling
      GSC self-renewal. Taken together, studies in this paper provide the first
      demonstration that Brm in the form of the PBAP complex functions in the GSC fate
      regulation. 

PMID- 25068273
TI  - In vivo imaging of Hedgehog pathway activation with a nuclear fluorescent
      reporter.
AB  - The Hedgehog (Hh) pathway is essential for embryonic development and tissue
      regeneration, and its dysregulation can lead to birth defects and tumorigenesis.
      Understanding how this signaling mechanism contributes to these processes would
      benefit from an ability to visualize Hedgehog pathway activity in live organisms,
      in real time, and with single-cell resolution. We report here the generation of
      transgenic zebrafish lines that express nuclear-localized mCherry fluorescent
      protein in a Gli transcription factor-dependent manner. As demonstrated by
      chemical and genetic perturbations, these lines faithfully report Hedgehog
      pathway state in individual cells and with high detection sensitivity. They will
      be valuable tools for studying dynamic Gli-dependent processes in vertebrates and
      for identifying new chemical and genetic regulators of the Hh pathway. 

PMID- 25068276
TI  - Impact of Hurricane Sandy on hospital emergency and dialysis services: a
      retrospective survey.
AB  - OBJECTIVE: Hurricane Sandy forced closures of many free-standing dialysis centers
      in New York City in 2012. Hemodialysis (HD) patients therefore sought dialysis
      treatments from nearby hospitals. The surge capacity of hospital dialysis
      services was the rate-limiting step for streamlining the emergency department
      flow of HD patients. The aim of this study was to determine the extent of the HD
      patients surge and to explore difficulties encountered by hospitals in Brooklyn,
      New York (USA) due to Hurricane Sandy. METHODS: A retrospective survey on
      hospital dialysis services was conducted by interviewing dialysis unit managers,
      focusing on the influx of HD patients from closed dialysis centers to hospitals,
      coping strategies these hospitals used, and difficulties encountered. RESULTS: In
      total, 347 HD patients presented to 15 Brooklyn hospitals for dialysis. The
      number of transient HD patients peaked two days after landfall and gradually
      decreased over a week. Hospital dialysis services reported issues with lack of
      dialysis documentation from transient dialysis patients (92.3%), staff shortage
      (50%), staff transportation (71.4%), and communication with other agencies
      (53.3%). Linear regression showed that factors significantly associated with
      enhanced surge capacity were the size of inpatient dialysis unit (P = .040),
      having affiliated outpatient dialysis centers (P = .032), using extra dialysis
      machines (P = .014), and having extra workforce (P = .007). Early emergency plan
      activation (P = .289) and shortening treatment time (P = .118) did not impact the
      surge capacity significantly in this study. CONCLUSION: These findings provide
      potential improvement options for receiving hospitals dialysis units to prepare
      for future events.

PMID- 25068277
TI  - A migrant left ventricular lead.

PMID- 25068282
TI  - Wound administration of M2-polarized macrophages does not improve murine
      cutaneous healing responses.
AB  - Macrophages play a crucial role in all stages of cutaneous wound healing
      responses and dysregulation of macrophage function can result in derailed wound
      repair. The phenotype of macrophages is influenced by the wound microenvironment
      and evolves during healing from a more pro-inflammatory (M1) profile in early
      stages, to a less inflammatory pro-healing (M2) phenotype in later stages of
      repair. The aim of the current study was to investigate the potential of
      exogenous administration of M2 macrophages to promote wound healing in an
      experimental mouse model of cutaneous injury. Bone marrow derived macrophages
      were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2
      polarized cells, M2a or M2c respectively. Polarized macrophages were injected
      into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db
      mice. Control groups were injected with non-polarized (M0) macrophages or saline.
      Our data indicate that despite M2 macrophages exhibit an anti-inflammatory
      phenotype in-vitro, they do not improve wound closure in wild type mice while
      they delay healing in diabetic mice. Examination of wounds on day 15 post-injury
      indicated delayed re-epithelialization and persistence of neutrophils in M2
      macrophage treated diabetic wounds. Therefore, topical application of ex-vivo
      generated M2 macrophages is not beneficial and contraindicated for cell therapy
      of skin wounds. 

PMID- 25068283
TI  - Measuring motivation for appetitive behaviour: food-restricted broiler breeder
      chickens cross a water barrier to forage in an area of wood shavings without
      food.
AB  - Broiler breeders (parents of meat chickens) are selected for fast growth and
      become obese if fed ad libitum. To avoid this and maintain good health and
      reproductive ability, they are feed restricted to about 1/3 of what they would
      eat ad libitum. As a result, they experience chronic hunger and exhibit abnormal
      behaviour patterns that may indicate stress and frustration. One approach to
      measuring hunger is to observe how much birds will work, such as pecking a key,
      for access to more or different types of food. However, the sight, smell, and
      feedback from consumption of the feed reward changes the context and may
      artificially raise feeding motivation. To avoid this, we tested broiler breeders
      in an apparatus in which they could work for access to a wooden platform covered
      in wood shavings by crossing a water runway which increased in length and depth
      in 8 successive tests. In the wood shavings area, they could perform exploratory
      and foraging behaviour (the appetitive phase of feeding) but were never rewarded
      with feed. Sixty birds were divided into three feed quantity treatments:
      commercial restriction (R), and twice (2R) or three times (3R) this amount.
      Overall, birds fed R worked harder to reach the wood shavings area (reached it in
      a larger number of tests) than 2R and 3R birds (P<0.001). More restricted birds
      took less time to reach the area (P<0.001, R<2R<3R) and spent more time foraging
      while there (P<0.001, R>2R>3R). This indicates that restricted-fed birds were
      hungry and willing to work for the opportunity to forage even though food was
      never provided, suggesting that their motivation to perform the appetitive
      component of feeding behaviour (foraging/food searching) was sufficient to
      sustain their response. Thus food restriction in broiler breeders is a welfare
      concern. However these methods could be used to test alternative feeding regimes
      to attempt to find ways of alleviating hunger while still maintaining healthy
      growth and reproduction in these birds. 

PMID- 25068284
TI  - Hysteresis can grant fitness in stochastically varying environment.
AB  - Although the existence of multiple stable phenotypes of living organisms enables
      random switching between phenotypes as well as non-random history dependent
      switching called hysteresis, only random switching has been considered in prior
      experimental and theoretical models of adaptation to variable environments. This
      work considers the possibility that hysteresis may also evolve together with
      random phenotype switching to maximize population growth. In addition to allowing
      the possibility that switching rates between different phenotypes may depend not
      only on a continuous environmental input variable, but also on the phenotype
      itself, the present work considers an opportunity cost of the switching events.
      This opportunity cost arises as a result of a lag phase experimentally observed
      after phenotype switching and stochastic behavior of the environmental input. It
      is shown that stochastic environmental variation results in maximal asymptotic
      growth rate when organisms display hysteresis for sufficiently slowly varying
      environmental input. At the same time, sinusoidal input does not cause evolution
      of memory suggesting that the connection between the lag phase, stochastic
      environmental variation and evolution of hysteresis is a result of a stochastic
      resonance type phenomenon. 

PMID- 25068274
TI  - Hepatitis C virus infection epidemiology among people who inject drugs in Europe:
      a systematic review of data for scaling up treatment and prevention.
AB  - BACKGROUND: People who inject drugs (PWID) are a key population affected by
      hepatitis C virus (HCV). Treatment options are improving and may enhance
      prevention; however access for PWID may be poor. The availability in the
      literature of information on seven main topic areas (incidence, chronicity,
      genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of
      disease) to guide HCV treatment and prevention scale-up for PWID in the 27
      countries of the European Union is systematically reviewed. METHODS AND FINDINGS:
      We searched MEDLINE, EMBASE and Cochrane Library for publications between 1
      January 2000 and 31 December 2012, with a search strategy of general keywords
      regarding viral hepatitis, substance abuse and geographic scope, as well as topic
      specific keywords. Additional articles were found through structured email
      consultations with a large European expert network. Data availability was highly
      variable and important limitations existed in comparability and
      representativeness. Nine of 27 countries had data on HCV incidence among PWID,
      which was often high (2.7-66/100 person-years, median 13, Interquartile range
      (IQR) 8.7-28). Most common HCV genotypes were G1 and G3; however, G4 may be
      increasing, while the proportion of traditionally 'difficult to treat' genotypes
      (G1+G4) showed large variation (median 53, IQR 43-62). Twelve countries reported
      on HCV chronicity (median 72, IQR 64-81) and 22 on HIV prevalence in HCV-infected
      PWID (median 3.9%, IQR 0.2-28). Undiagnosed infection, assessed in five
      countries, was high (median 49%, IQR 38-64), while of those diagnosed, the
      proportion entering treatment was low (median 9.5%, IQR 3.5-15). Burden of
      disease, where assessed, was high and will rise in the next decade. CONCLUSION:
      Key data on HCV epidemiology, care and disease burden among PWID in Europe are
      sparse but suggest many undiagnosed infections and poor treatment uptake.
      Stronger efforts are needed to improve data availability to guide an increase in
      HCV treatment among PWID.

PMID- 25068285
TI  - Positive symptoms in first-episode psychosis patients experiencing low maternal
      care and stressful life events: a pilot study to explore the role of the COMT
      gene.
AB  - COMT Val(158)Met moderates the effect of stress on psychotic symptoms. Exposure
      to stress is also associated with mesolimbic dopamine release in individuals
      experiencing low maternal care. We therefore test the hypothesis that recent
      stressful life events are associated with more severe positive symptoms
      (associated with mesolimbic dopamine release) in first-episode psychosis (FEP)
      patients who experienced low maternal care during childhood. We hypothesized that
      COMT Val(158)Met moderates this association. A total of 149 FEP patients
      recruited within the Psychosis Incident Cohort Outcome Study (PICOS) participated
      in the present study. Maternal care was assessed by the Parental Bonding
      Instrument (PBI), stressful life events were collected by the List of Events
      Scale and positive symptoms were assessed by the Positive and Negative Syndrome
      Scale (PANSS). We found that low maternal care and recent stressful life events
      were associated with higher level of positive symptoms at the onset (analysis of
      variance [ANOVA], p = 0.012), and that patients who were also homozygotes for the
      COMT Val(158) allele had the highest level of positive symptoms (ANOVA, p =
      0.024). Low maternal care and severe stressful life events may contribute to a
      symptomatology characterized by more severe positive symptoms at the onset,
      possibly due to an increased mesolimbic dopamine release. Homozygosity for the
      COMT Val(158) allele seems to confer a biological predisposition to the stress
      related hyperactivity of the mesolimbic dopaminergic system. The data imply that
      the mesolimbic dopaminergic system is involved in the mediation/modulation of the
      effect of stressful events on the vulnerability for psychosis.

PMID- 25068288
TI  - Aggregatibacter actinomycemcomitans pneumonia in children: two case reports and a
      review of the literature.
AB  - Aggregatibacter actinomycemcomitans, previously named Actinobacillus
      actinomycetemcomitans (Aa), is a facultative Gram-negative slow-growing
      coccobacillus associated with severe oral and nonoral infections. It is a member
      of the HACEK group. Pulmonary infection caused by Aa is rare. We describe two
      cases of Aa pneumonia mimicking malignancy and review published pediatric cases. 

PMID- 25068289
TI  - Mild influenza A/H7N9 infection among children in Guangdong Province.
AB  - We describe the clinical and epidemiologic characteristics of 7 children infected
      with A/H7N9 in Guangdong Province during the winter of 2013-2014. Our results
      indicate that the mild or asymptomatic characteristics common in H7N9-infected
      children could pose challenges to our surveillance system becoming a hidden
      threat to the public health of China and the world. 

PMID- 25068287
TI  - Prevalence of lipodystrophy and metabolic abnormalities in HIV-infected African
      children after 3 years on first-line antiretroviral therapy.
AB  - BACKGROUND: Most pediatric lipodystrophy data come from high-income/middle-income
      countries, but most HIV-infected children live in sub-Saharan Africa, where
      lipodystrophy studies have predominantly investigated stavudine-based regimens.
      METHODS: Three years after antiretroviral therapy (ART) initiation, body
      circumferences and skinfold thicknesses were measured (n = 590), and fasted lipid
      profile assayed (n = 325), in children from 2 ARROW trial centres in
      Uganda/Zimbabwe. Analyses compared randomization to long-term versus short-term
      versus no zidovudine from ART initiation [unadjusted; latter 2 groups receiving
      abacavir+lamivudine+non-nucleoside-reverse-transciptase-inhibitor (nNRTI) long
      term], and nonrandomized (confounder-adjusted) receipt of nevirapine versus
      efavirenz. RESULTS: Body circumferences and skinfold thicknesses were similar
      regardless of zidovudine exposure (P > 0.1), except for subscapular and supra
      iliac skinfolds-for-age which were greater with long-term zidovudine (0.006 < P <
      0.047). Circumferences/skinfolds were also similar with efavirenz and nevirapine
      (adjusted P > 0.09; 0.02 < P < 0.03 for waist/waist-hip-ratio). Total and high
      density lipoprotein (HDL)-cholesterol, HDL/triglyceride-ratio (P < 0.0001) and
      triglycerides (P = 0.01) were lower with long-term zidovudine. Low-density
      lipoprotein (LDL)-cholesterol was higher with efavirenz than nevirapine (P <
      0.001). Most lipids remained within normal ranges (75% cholesterol, 85% LDL and
      100% triglycerides) but more on long-term zidovudine (3 NRTI) had abnormal HDL
      cholesterol (88% vs. 40% short/no-zidovudine, P < 0.0001). Only 8/579(1.4%)
      children had clinical fat wasting (5 grade 1; 3 grade 2); 2(0.3%) had grade 1 fat
      accumulation. CONCLUSIONS: Long-term zidovudine-based ART is associated with
      similar body circumferences and skinfold thicknesses to abacavir-based ART, with
      low rates of lipid abnormalities and clinical lipodystrophy, providing
      reassurance where national programs now recommend long-term zidovudine. Efavirenz
      and nevirapine were also similar; however, the higher LDL observed with efavirenz
      and lower HDL observed with zidovudine suggests that
      zidovudine+lamivudine+efavirenz should be investigated in future.

PMID- 25068290
TI  - Novel assessment tools to evaluate clinical and laboratory responses in a subset
      of patients enrolled in the Rituximab in Myositis trial.
AB  - OBJECTIVES: We aimed to assess changes in myositis core set measures and
      ancillary clinical and laboratory data from the National Institutes of Health's
      subset of patients enrolled in the Rituximab in Myositis trial. METHODS: Eighteen
      patients (5 dermatomyositis, 8 polymyositis, 5 juvenile dermatomyositis)
      completed more in-depth testing of muscle strength and cutaneous assessments,
      patient-reported outcomes, and laboratory tests before and after administration
      of rituximab. Percentage change in individual measures and in the definitions of
      improvement (DOIs) and standardized response means were examined over 44 weeks.
      RESULTS: Core set activity measures improved by 18-70% from weeks 0-44 and were
      sensitive to change. Fifteen patients met the DOI at week 44, 9 patients met a
      DOI 50% response, and 4 met a DOI 70% response. Muscle strength and function
      measures were more sensitive to change than cutaneous assessments.
      Constitutional, gastrointestinal, and pulmonary systems improved 44-70%. Patient
      reported outcomes improved up to 28%. CD20+ B cells were depleted in the
      periphery, but B cell depletion was not associated with clinical improvement at
      week 16. CONCLUSIONS: This subset of patients had high rates of clinical response
      to rituximab, similar to patients in the overall trial. Most measures were
      responsive, and muscle strength had a greater degree of change than cutaneous
      assessments. Several novel assessment tools, including measures of strength and
      function, extra-muscular organ activity, fatigue, and health-related quality of
      life, are promising for use in future myositis trials. Further study of B cell
      depleting therapies in myositis, particularly in treatment-naive patients, is
      warranted.

PMID- 25068291
TI  - Nontuberculous mycobacteria among patients with cystic fibrosis in the United
      States: screening practices and environmental risk.
AB  - RATIONALE: Persons with cystic fibrosis (CF) are at greater risk of
      nontuberculous mycobacterial (NTM) infections than the general population.
      However, among patients with CF, geographic variation in prevalence is poorly
      understood. OBJECTIVES: To describe the prevalence and screening practices of NTM
      among U.S. patients with CF. METHODS: CF Patient Registry data from 2010-2011
      were obtained to estimate the prevalence of NTM among patients with CF 12 years
      of age or older by state. Climatic data were also obtained and predictors of NTM
      infection analyzed using regression analysis. Geographic clustering and
      mycobacterial culture rates by state were also assessed. MEASUREMENTS AND MAIN
      RESULTS: Among patients with CF 12 years of age or older, 58% had mycobacterial
      cultures; 14% were positive for NTM. Most states (n = 31) had a prevalence of 10
      20%; seven states predominantly in the West and Southeast had a prevalence of 20%
      or greater, including Alaska, which cultured patients more frequently than any
      other state. Nearly 60% of positive cultures were for Mycobacterium avium
      complex, although this ranged by state, from 29% in Louisiana to 100% for
      Nebraska/Delaware. Significant (P < 0.002) spatial clustering of NTM was
      detected, centering in Wisconsin, Arizona, Florida, and Maryland. Higher
      saturated vapor pressure increased risk for NTM (odds ratio = 1.06; 95%
      confidence interval = 1.02-1.10). The proportion of patients cultured for
      mycobacteria varied greatly by state of residence (median = 46%; range = 9-73%).
      CONCLUSIONS: NTM prevalence varies significantly among patients with CF by
      geographic area, and is largely influenced by environmental factors. However, NTM
      culture practices vary greatly, with some high-prevalence states screening less
      than 25% annually. Routine screening for all patients with CF is needed for
      timely detection.

PMID- 25068292
TI  - Differential peripheral blood gene expression profile based on Her2 expression on
      primary tumors of breast cancer patients.
AB  - Breast cancer prognosis and treatment is highly dependent on the molecular
      features of the primary tumors. These tumors release specific molecules into the
      environment that trigger characteristic responses into the circulatory cells. In
      this study we investigated the expression pattern of 84 genes known to be
      involved in breast cancer signaling in the peripheral blood of breast cancer
      patients with ER-, PR- primary tumors. The patients were grouped according to
      Her2 expression on the primary tumors in Her2+ and Her2- cohorts. Transcriptional
      analysis revealed 15 genes to be differentially expressed between the two groups
      highlighting that Her2 signaling in primary tumors could be associated with
      specific blood gene expression. We found CCNA1 to be up-regulated, while ERBB2,
      RASSF1, CDH1, MKI67, GATA3, GLI1, SFN, PTGS2, JUN, NOTCH1, CTNNB1, KRT8, SRC, and
      HIC1 genes were down-regulated in the blood of triple negative breast cancer
      patients compared to Her2+ cohort. IPA network analysis predicts that the
      identified genes are interconnected and regulate each other. These genes code for
      cell cycle regulators, cell adhesion molecules, transcription factors or signal
      transducers that modulate immune signaling, several genes being also associated
      with cancer progression and treatment response. These results indicate an altered
      immune signaling in the peripheral blood of triple negative breast cancer
      patients. The involvement of the immune system is necessary in favorable
      treatment response, therefore these results could explain the low response rates
      observed for triple negative breast cancer patients. 

PMID- 25068293
TI  - A new method for assessing how sensitivity and specificity of linkage studies
      affects estimation.
AB  - BACKGROUND: While the importance of record linkage is widely recognised, few
      studies have attempted to quantify how linkage errors may have impacted on their
      own findings and outcomes. Even where authors of linkage studies have attempted
      to estimate sensitivity and specificity based on subjects with known status, the
      effects of false negatives and positives on event rates and estimates of effect
      are not often described. METHODS: We present quantification of the effect of
      sensitivity and specificity of the linkage process on event rates and incidence,
      as well as the resultant effect on relative risks. Formulae to estimate the true
      number of events and estimated relative risk adjusted for given linkage
      sensitivity and specificity are then derived and applied to data from a prisoner
      mortality study. The implications of false positive and false negative matches
      are also discussed. DISCUSSION: Comparisons of the effect of sensitivity and
      specificity on incidence and relative risks indicate that it is more important
      for linkages to be highly specific than sensitive, particularly if true incidence
      rates are low. We would recommend that, where possible, some quantitative
      estimates of the sensitivity and specificity of the linkage process be performed,
      allowing the effect of these quantities on observed results to be assessed.

PMID- 25068294
TI  - High glucose alters retinal astrocytes phenotype through increased production of
      inflammatory cytokines and oxidative stress.
AB  - Astrocytes are macroglial cells that have a crucial role in development of the
      retinal vasculature and maintenance of the blood-retina-barrier (BRB). Diabetes
      affects the physiology and function of retinal vascular cells including
      astrocytes (AC) leading to breakdown of BRB. However, the detailed cellular
      mechanisms leading to retinal AC dysfunction under high glucose conditions remain
      unclear. Here we show that high glucose conditions did not induce the apoptosis
      of retinal AC, but instead increased their rate of DNA synthesis and adhesion to
      extracellular matrix proteins. These alterations were associated with changes in
      intracellular signaling pathways involved in cell survival, migration and
      proliferation. High glucose conditions also affected the expression of
      inflammatory cytokines in retinal AC, activated NF-kappaB, and prevented their
      network formation on Matrigel. In addition, we showed that the attenuation of
      retinal AC migration under high glucose conditions, and capillary morphogenesis
      of retinal endothelial cells on Matrigel, was mediated through increased
      oxidative stress. Antioxidant proteins including heme oxygenase-1 and
      peroxiredoxin-2 levels were also increased in retinal AC under high glucose
      conditions through nuclear localization of transcription factor nuclear factor
      erythroid 2-related factor-2. Together our results demonstrated that high glucose
      conditions alter the function of retinal AC by increased production of
      inflammatory cytokines and oxidative stress with significant impact on their
      proliferation, adhesion, and migration. 

PMID- 25068295
TI  - Oxygen sensing with ion channels.

PMID- 25068297
TI  - Development of a measure to predict short-term violence in psychiatric
      populations: The Imminent Risk Rating Scale.
AB  - The prediction of near-term violence among psychiatric inpatients has become an
      important goal in recent years. The Imminent Risk Rating Scale (IRRS) is a
      screening tool that has been designed to enhance clinicians' knowledge of their
      patients' risk of violence in the hours and days following evaluation. Drawing on
      the imminent-violence literature, the instrument includes 7 items touching on
      personal, interpersonal, and environmental variables that are uniquely predictive
      of short-term violence. The present study reports on the findings of a small
      scale test of the effectiveness and psychometric properties of the IRRS among a
      sample of psychiatric inpatients (N = 121) undergoing pretrial forensic
      psychiatric evaluations. The measure has desirable interrater reliability,
      demonstrates robust improvement over chance in identifying which patients will
      engage in violence over a subsequent 2-week period, and is especially effective
      in identifying individuals who are not violent during that time period.

PMID- 25068296
TI  - Lymphatic endothelial cells support tumor growth in breast cancer.
AB  - Tumor lymphatic vessels (LV) serve as a conduit of tumor cell dissemination, due
      to their leaky nature and secretion of tumor-recruiting factors. Though lymphatic
      endothelial cells (LEC) lining the LV express distinct factors (also called
      lymphangiocrine factors), these factors and their roles in the tumor
      microenvironment are not well understood. Here we employ LEC, microvascular
      endothelial cells (MEC), and human umbilical vein endothelial cells (HUVEC)
      cultured in triple-negative MDA-MB-231 tumor-conditioned media (TCM) to determine
      the factors that may be secreted by various EC in the MDA-MB-231 breast tumor.
      These factors will serve as endothelium derived signaling molecules in the tumor
      microenvironment. We co-injected these EC with MDA-MB-231 breast cancer cells
      into animals and showed that LEC support tumor growth, HUVEC have no significant
      effect on tumor growth, whereas MEC suppress it. Focusing on LEC-mediated tumor
      growth, we discovered that TCM-treated LEC ('tumor-educated LEC') secrete high
      amounts of EGF and PDGF-BB, compared to normal LEC. LEC-secreted EGF promotes
      tumor cell proliferation. LEC-secreted PDGF-BB induces pericyte infiltration and
      angiogenesis. These lymphangiocrine factors may support tumor growth in the tumor
      microenvironment. This study shows that LV serve a novel role in the tumor
      microenvironment apart from their classical role as conduits of metastasis. 

PMID- 25068298
TI  - Assessing functional impairment in a working military population: the Walter Reed
      functional impairment scale.
AB  - Measurement of functional impairment is a priority for the military and other
      professional work groups routinely exposed to stressful traumatic events as part
      of their occupation. Standard measures of impairment used in general or
      chronically ill populations contain many items not suitable for these
      populations, and include mental health symptoms items that are not true measures
      of functioning. We created a new, 14-item scale-the Walter Reed Functional
      Impairment Scale-to assess functioning in 4 domains (physical, occupational,
      social, and personal). We asked 3,380 soldiers how much difficulty they currently
      have in each of the 4 domains on a 5-point scale. Behaviorally based psychosocial
      and occupational performance measures and general health questions were used to
      validate the scale. The utility of the scale was assessed against clinical
      measures of psychopathology and physical health (depression, posttraumatic stress
      disorder [PTSD], general health, generalized physical symptoms). We utilized
      Cronbach's alpha, item response theory, and the score test for trend to establish
      consistency of items and the validity of the scale. The scale exhibited excellent
      reliability (Cronbach's alpha= 0.92) and validity. The individual items and
      quartiles of sum scores were strongly correlated with negative occupational and
      social performance, and the utility of the scale was demonstrated by strong
      correlations with depression, PTSD, and high levels of generalized physical
      symptoms. This scale exhibits excellent psychometric properties in this sample of
      U.S. soldiers and, pending future research, is likely to have utility for other
      healthy occupational groups.

PMID- 25068299
TI  - Accurate and computationally efficient prediction of thermochemical properties of
      biomolecules using the generalized connectivity-based hierarchy.
AB  - In this study we have used the connectivity-based hierarchy (CBH) method to
      derive accurate heats of formation of a range of biomolecules, 18 amino acids and
      10 barbituric acid/uracil derivatives. The hierarchy is based on the connectivity
      of the different atoms in a large molecule. It results in error-cancellation
      reaction schemes that are automated, general, and can be readily used for a broad
      range of organic molecules and biomolecules. Herein, we first locate stable
      conformational and tautomeric forms of these biomolecules using an accurate level
      of theory (viz. CCSD(T)/6-311++G(3df,2p)). Subsequently, the heats of formation
      of the amino acids are evaluated using the CBH-1 and CBH-2 schemes and routinely
      employed density functionals or wave function-based methods. The calculated heats
      of formation obtained herein using modest levels of theory and are in very good
      agreement with those obtained using more expensive W1-F12 and W2-F12 methods on
      amino acids and G3 results on barbituric acid derivatives. Overall, the present
      study (a) highlights the small effect of including multiple conformers in
      determining the heats of formation of biomolecules and (b) in concurrence with
      previous CBH studies, proves that use of the more effective error-cancelling
      isoatomic scheme (CBH-2) results in more accurate heats of formation with
      modestly sized basis sets along with common density functionals or wave function
      based methods. 

PMID- 25068301
TI  - Does self-reporting facilitate history taking in food poisoning mass-casualty
      incidents?
AB  - INTRODUCTION: Medical history is an important contributor to diagnosis and
      patient management. In mass-casualty incidents (MCIs), health care providers are
      often overwhelmed by large numbers of casualties. An efficient, reliable, and
      affordable method of information collection is essential for effective health
      care response. HYPOTHESIS/PROBLEM: In some MCIs, self-reporting of symptoms can
      decrease the time required for history taking, without sacrificing the
      completeness of triage information. METHODS: Two resident doctors and a number of
      seventh graders who had previous experience of abdominal discomfort were invited
      to join this study. A questionnaire was developed to collect information on
      common symptoms in food poisoning. Each question was scored, and enrolled
      students were randomly divided into two groups. The experimental group students
      answered the questionnaire first and then were interviewed to complete the
      medical history. The control group students were interviewed in the traditional
      way to collect medical history. Time of all interviews was measured and recorded.
      The time needed to complete the history taking and completeness of obtained
      information were compared with students' t tests, or Mann-Whitney U tests, based
      on the normality of data. Comprehensibility of each question, scored by enrolled
      students, was reported by descriptive statistics. RESULTS: There were 41 students
      enrolled: 22 in the experimental group and 19 in the control group. Time to
      complete history taking in the experimental group (163.0 seconds, SD=52.3) was
      shorter than that in the control group (198.7 seconds, SD=40.9) (P=.010). There
      was no difference in the completeness of history obtained between the
      experimental group and the control group (94.8%, SD=5.0 vs 94.2%, SD=6.1;
      P=.747). Between the two doctors, no significant difference was found in the time
      required for history taking (185.2 seconds, SD=42.2 vs 173.1 seconds, SD=58.6;
      P=.449), or the completeness of information (94.1%, SD=5.9 vs 95.0%, SD=5.0;
      P=.601). Most of the questions were scored "good" in comprehensibility.
      CONCLUSION: Self-reporting of symptoms can shorten the time of history taking
      during a food poisoning mass-casualty event without sacrificing the completeness
      of information.

PMID- 25068300
TI  - Quantitative comparison of tumor delivery for multiple targeted nanoparticles
      simultaneously by multiplex ICP-MS.
AB  - Given the rapidly expanding library of disease biomarkers and targeting agents,
      the number of unique targeted nanoparticles is growing exponentially. The high
      variability and expense of animal testing often makes it unfeasible to examine
      this large number of nanoparticles in vivo. This often leads to the investigation
      of a single formulation that performed best in vitro. However, nanoparticle
      performance in vivo depends on many variables, many of which cannot be adequately
      assessed with cell-based assays. To address this issue, we developed a lanthanide
      doped nanoparticle method that allows quantitative comparison of multiple
      targeted nanoparticles simultaneously. Specifically, superparamagnetic iron oxide
      (SPIO) nanoparticles with different targeting ligands were created, each with a
      unique lanthanide dopant. Following the simultaneous injection of the various
      SPIO compositions into tumor-bearing mice, inductively coupled plasma mass
      spectroscopy was used to quantitatively and orthogonally assess the concentration
      of each SPIO composition in serial blood and resected tumor samples. 

PMID- 25068302
TI  - Stock portfolio structure of individual investors infers future trading behavior.
AB  - Although the understanding of and motivation behind individual trading behavior
      is an important puzzle in finance, little is known about the connection between
      an investor's portfolio structure and her trading behavior in practice. In this
      paper, we investigate the relation between what stocks investors hold, and what
      stocks they buy, and show that investors with similar portfolio structures to a
      great extent trade in a similar way. With data from the central register of
      shareholdings in Sweden, we model the market in a similarity network, by
      considering investors as nodes, connected with links representing portfolio
      similarity. From the network, we find investor groups that not only identify
      different investment strategies, but also represent individual investors trading
      in a similar way. These findings suggest that the stock portfolios of investors
      hold meaningful information, which could be used to earn a better understanding
      of stock market dynamics. 

PMID- 25068304
TI  - Role of advanced glycation end-products in obesity-related ovarian dysfunction.
AB  - Obesity affects ovarian function, one of the main regulators of female fertility.
      Tissue levels of the proinflammatory advanced glycation end-products (AGEs) and
      their receptors (RAGE) are elevated in obesity. AGEs are key contributors to
      perturbations in the ovarian microenvironment. On this basis, the present review
      focuses on clinical and experimental studies supporting the role of AGE-RAGE
      system as a contributor to obesity-related ovarian dysfunction. Particular
      emphasis has been given to changes in AGEs, RAGE and the anti-inflammatory
      soluble receptor (sRAGE) levels in obesity state and following dietary
      interventions (high-fat diet and weight loss). Ovarian sensitivity, in particular
      granulosa cell function and oocyte meiosis, to the pro-inflammatory AGE-RAGE
      system as well as the relationship of follicular fluid AGEs and sRAGE to in vitro
      fertilization outcome are also discussed. Overall, obesity, with its alterations
      in the AGE-RAGE system, can disrupt the ovarian microenvironment potentially
      compromising oocyte competence and fertility. This review underscores a critical
      need to uncover the mechanistic actions of AGE-RAGE system in obesity-related
      ovarian dysfunction. Clinical and basic studies focusing on elucidating the
      patterns of accumulation and role of the AGE-RAGE system in human ovarian
      follicles are key steps in understanding their contribution to the health of
      human oocytes and embryos. 

PMID- 25068303
TI  - Efficient expression of functional (alpha6beta2)2beta3 AChRs in Xenopus oocytes
      from free subunits using slightly modified alpha6 subunits.
AB  - Human (alpha6beta2)(alpha4beta2)beta3 nicotinic acetylcholine receptors (AChRs)
      are essential for addiction to nicotine and a target for drug development for
      smoking cessation. Expressing this complex AChR is difficult, but has been
      achieved using subunit concatamers. In order to determine what limits expression
      of alpha6* AChRs and to efficiently express alpha6* AChRs using free subunits, we
      investigated expression of the simpler (alpha6beta2)2beta3 AChR. The concatameric
      form of this AChR assembles well, but is transported to the cell surface
      inefficiently. Various chimeras of alpha6 with the closely related alpha3 subunit
      increased expression efficiency with free subunits and produced pharmacologically
      equivalent functional AChRs. A chimera in which the large cytoplasmic domain of
      alpha6 was replaced with that of alpha3 increased assembly with beta2 subunits
      and transport of AChRs to the oocyte surface. Another chimera replacing the
      unique methionine 211 of alpha6 with leucine found at this position in
      transmembrane domain 1 of alpha3 and other alpha subunits increased assembly of
      mature subunits containing beta3 subunits within oocytes. Combining both alpha3
      sequences in an alpha6 chimera increased expression of functional
      (alpha6beta2)2beta3 AChRs to 12-fold more than with concatamers. This is
      pragmatically useful, and provides insights on features of alpha6 subunit
      structure that limit its expression in transfected cells. 

PMID- 25068305
TI  - Methane intestinal production and poor metabolic control in type I diabetes
      complicated by autonomic neuropathy.
AB  - AIM: At the state of art it's unknown the correlation between diabetes and lower
      gastrointestinal disorders. Some studies show a significantly higher prevalence
      of small intestinal bacterial overgrowth in patients with type I diabetes in
      particular complicated by autonomic neuropathy. No data exists about
      gastrointestinal methane production in patients with diabetes and autonomic
      diabetic neuropathy. The aim of this paper was to evaluate the correlation of
      small intestinal bacterial overgrowth and gastrointestinal methane production
      with metabolic control and daily insulin requirements in patients with type 1
      diabetes and. autonomic diabetic neuropathy. METHODS: Thirty subjects with type 1
      diabetes and autonomic diabetic neuropathy were underwent hydrogen and methane
      lactulose breath test (LBT) to evaluate the presence of small intestinal
      bacterial overgrowth (double peak of hydrogen) and methane production. The
      metabolic control was evaluated through the glycated hemoglobin and the daily
      insulin requirement (calculated as ratio between total insulin units in a day and
      body weight). Methane producers were treated with metronidazole (500 mg bid for
      10 days) and perform a LBT 8 weeks after the end of therapy RESULTS: Eight over
      thirty patients (26.6%) met the diagnostic criteria for small intestinal
      bacterial overgrowth. 11/30 patients (36%) were methane-producers (mean baseline
      value 16.37 +/- 13.01 ppm; mean peak 26.62 +/- 11.41 ppm); interestingly this
      subset of patients showed a worse glycemic control (mean HbA1c 8.16 +/- 0.9% vs.
      7.49 +/- 0.8%, P<0.05). After metronidazole therapy 7/11 (63.3%) reduced CH4
      production and they showed a mean HbA1c significantly lower than corresponding
      value before antibiotic therapy (7.63 +/- 0.7% vs. 8.25 +/- 0.8%). CONCLUSION:
      Our study showed for the first time a possible role of CH4 production in
      metabolic control. In particular, the most interesting data is that an increased
      values of HbA1c seems to be related to a gut CH4 production as confirmed by its
      significant improvement after eradication therapy. We are not yet able to
      determine whether poor glycemic control is the cause or the consequence of the
      selection of methanogenic flora.

PMID- 25068306
TI  - Serum nesfatin-1 levels in overt and subclinical hyperthyroidism.
AB  - AIM: Nesfatin-1 was recently discovered anorexigenic peptide in the brain which
      is derived from nucleobindin-2. Central and peripheral administration of nesfatin
      1, inhibits food intake, dose-dependently. Hyperthyroid patients have increased
      appetite and food intake with a craving for carbohydrate-rich food, at the
      beginning of disease, but the physiological mechanisms underlying this behavior
      is not known exactly. In this study, we investigated whether nesfatin-1 is
      involved in the regulation of appetite and body weight in hyperthyroidism, or
      not. METHODS: A total of 70 patients with subclinical (35) and overt
      hyperthyroidism (35) compared with 35 control patients. Serum nesfatin-1 level
      was measured from all samples by commercial ELISA kit. RESULTS: Serum nesfatin-1
      levels were similar between three groups (P=0.293). After adjusting for age and
      body mass index, nesfatin-1 levels in control group was not different from
      subclinical and overt hyperthyroid group, respectively (P=0.567 and P=0.519).
      CONCLUSION: These data showed that serum nesfatin-1 levels do not significant
      change in overt and subclinical hyperthyroidism.

PMID- 25068307
TI  - Diagnosis of late-onset congenital adrenal hyperplasia in clinical practice:
      current evaluation.
AB  - AIM: Aim of the study was to investigate the need to perform the
      adrenocorticotropic hormone (ACTH) stimulation test by recognizing the importance
      of a second look at basal serum 17-alpha hydroxyprogesterone (17-OHP) levels and
      calculating new serum 17-OHP cut-off level. METHODS: A total of 142 patients who
      had hyperandrogenism symptoms and had basal serum 17-OHP levels of higher than
      1.3 ng/mL were scheduled to have an ACTH stimulation test performed. Prior to
      ACTH stimulation, 17-OHP levels were recorded and as second-look levels. RESULTS:
      Patients were divided to two groups, late-onset congenital adrenal hyperplasia
      (LOCAH) (25/142), non-LOCAH (117/142). There were statistically significant
      results related to cycle length and menstrual irregularity between two groups
      (P=0.042, P=0.041, respectively). In the LOCAH group, basal serum 17 OHP levels
      were higher than non-LOCAH (P=0.001). When basal serum 17-OHP levels were
      measured a second time, the need for performing the ACTH stimulation test was
      decreased. According to cut-off levels of 1.3 ng/mL, 100% of patients needing to
      take the second serum 17-OHP decreased to 83.1%, a cut-off level of 2 ng/mL
      decreased numbers from 74.65% to 35.92% and for 2.25 ng/mL 58.42% of patients was
      decreased to 26.77%. In this study we established 2.25 ng/ml is a superior cut
      off level for 17-OHP, its sensitivity is 84% and specifity is 50.4%. CONCLUSION:
      The incidence of LOCAH is 1.35% among the patients with hyperandrogenism
      symptoms. We found a single measurement of serum 17-OHP level can be unreliable.
      Second 17-OHP test reduces the need of performing the ACTH stimulation test by
      approximately 30%.

PMID- 25068308
TI  - Renal replacement therapy as a treatment for severe refractory hypercalcemia.

PMID- 25068309
TI  - Lanthanum from a modified clay used in eutrophication control is bioavailable to
      the marbled crayfish (Procambarus fallax f. virginalis).
AB  - To mitigate eutrophication in fresh standing waters the focus is on phosphorus
      (P) control, i.e. on P inflows to a lake as well as a lake's sediment as internal
      P source. The in-lake application of the lanthanum (La) modified clays - i.e. La
      modified bentonite (Phoslock) or La modified kaolinite, aim at dephosphatising
      the water column and at reducing the release of P from a lake's sediment.
      Application of these clays raises the question whether La from these clays can
      become bioavailable to biota. We investigated the bioavailability of La from
      Phoslock in a controlled parallel groups experiment in which we measured the La
      in carapace, gills, ovaries, hepatopancreas and abdominal muscle after 0, 14 and
      28 days of exposure to Phoslock. Expressing the treatment effect as the
      difference of the median concentration between the two treatment groups (Phoslock
      minus control group) yield the following effects, the plus sign (+) indicating an
      increase, concentrations in ug g(-1) dry weight: Day 14: carapace +10.5 ug g(-1),
      gills +112 ug g(-1), ovaries +2.6 ug g(-1), hepatopancreas +32.9 ug g(-1) and
      abodminal muscle +3.2 ug g(-1). Day 28: carapace +17.9 ug g(-1); gills +182 ug g(
      1); ovaries +2.2 ug g(-1); hepatopancreas +41.9 ug g(-1) and abdominal muscle
      +7.6 ug g(-1), all effects were statistically significant. As La from Phoslock is
      bio-available to and taken up by the marbled crayfishes (Procambarus fallax f.
      virginalis), we advocate that the application of in-lake chemical water
      treatments to mitigate eutrophication should be accompanied by a thorough study
      on potential side effects.

PMID- 25068313
TI  - Rheology of red blood cells under flow in highly confined microchannels. II.
      Effect of focusing and confinement.
AB  - We study the focusing of red blood cells and vesicles in pressure-driven flows in
      highly confined microchannels (10-30 MUm), identifying the control parameters
      that dictate the cell distribution along the channel. Our results show that an
      increase in the flow velocity leads to a sharper cell distribution in a lateral
      position of the channel. This position depends on the channel width, with cells
      flowing at outer (closer to the walls) positions in thicker channels. We also
      study the relevance of the object shape, exploring the different behaviour of red
      blood cells and different vesicles. We also analyze the implications of these
      phenomena in the cell suspension rheology, highlighting the crucial role of the
      wall confinement in the rheological properties of the suspension. 

PMID- 25068311
TI  - Altered antioxidant system stimulates dielectric barrier discharge plasma-induced
      cell death for solid tumor cell treatment.
AB  - This study reports the experimental findings and plasma delivery approach
      developed at the Plasma Bioscience Research Center, Korea for the assessment of
      antitumor activity of dielectric barrier discharge (DBD) for cancer treatment.
      Detailed investigation of biological effects occurring after atmospheric pressure
      non-thermal (APNT) plasma application during in vitro experiments revealed the
      role of reactive oxygen species (ROS) in modulation of the antioxidant defense
      system, cellular metabolic activity, and apoptosis induction in cancer cells. To
      understand basic cellular mechanisms, we investigated the effects of APNT DBD
      plasma on antioxidant defense against oxidative stress in various malignant cells
      as well as normal cells. T98G glioblastoma, SNU80 thyroid carcinoma, KB oral
      carcinoma and a non-malignant HEK293 embryonic human cell lines were treated with
      APNT DBD plasma and cellular effects due to reactive oxygen species were
      observed. Plasma significantly decreased the metabolic viability and
      clonogenicity of T98G, SNU80, KB and HEK293 cell lines. Enhanced ROS in the cells
      led to death via alteration of total antioxidant activity, and NADP+/NADPH and
      GSH/GSSG ratios 24 hours (h) post plasma treatment. This effect was confirmed by
      annexin V-FITC and propidium iodide staining. These consequences suggested that
      the failure of antioxidant defense machinery, with compromised redox status,
      might have led to sensitization of the malignant cells. These findings suggest a
      promising approach for solid tumor therapy by delivering a lethal dose of APNT
      plasma to tumor cells while sparing normal healthy tissues. 

PMID- 25068314
TI  - Thyrotropin in San Diego: echoes after nearly a century.

PMID- 25068310
TI  - A systemic evaluation of cardiac differentiation from mRNA reprogrammed human
      induced pluripotent stem cells.
AB  - Genetically unmodified cardiomyocytes mandated for cardiac regenerative therapy
      is conceivable by "foot-print free" reprogramming of somatic cells to induced
      pluripotent stem cells (iPSC). In this study, we report generation of foot-print
      free hiPSC through messenger RNA (mRNA) based reprograming. Subsequently, we
      characterize cardiomyocytes derived from these hiPSC using molecular and
      electrophysiological methods to characterize their applicability for regenerative
      medicine. Our results demonstrate that mRNA-iPSCs differentiate ontogenetically
      into cardiomyocytes with increased expression of early commitment markers of
      mesoderm, cardiac mesoderm, followed by cardiac specific transcriptional and
      sarcomeric structural and ion channel genes. Furthermore, these cardiomyocytes
      stained positively for sarcomeric and ion channel proteins. Based on multi
      electrode array (MEA) recordings, these mRNA-hiPSC derived cardiomyocytes
      responded predictably to various pharmacologically active drugs that target
      adrenergic, sodium, calcium and potassium channels. The cardiomyocytes responded
      chronotropically to isoproterenol in a dose dependent manner, inotropic activity
      of nifidipine decreased spontaneous contractions. Moreover, Sotalol and E-4031
      prolonged QT intervals, while TTX reduced sodium influx. Our results for the
      first time show a systemic evaluation based on molecular, structural and
      functional properties of cardiomyocytes differentiated from mRNA-iPSC. These
      results, coupled with feasibility of generating patient-specific iPSCs hold great
      promise for the development of large-scale generation of clinical grade
      cardiomyocytes for cardiac regenerative medicine. 

PMID- 25068315
TI  - Vaccines against bovine babesiosis: where we are now and possible roads ahead.
AB  - SUMMARY Bovine babesiosis caused by the tick-transmitted haemoprotozoans Babesia
      bovis, Babesia bigemina and Babesia divergens commonly results in substantial
      cattle morbidity and mortality in vast world areas. Although existing live
      vaccines confer protection, they have considerable disadvantages. Therefore,
      particularly in countries where large numbers of cattle are at risk, important
      research is directed towards improved vaccination strategies. Here a
      comprehensive overview of currently used live vaccines and of the status quo of
      experimental vaccine trials is presented. In addition, pertinent research fields
      potentially contributing to the development of novel non-live and/or live
      vaccines are discussed, including parasite antigens involved in host cell
      invasion and in pathogen-tick interactions, as well as the protective immunity
      against infection. The mining of available parasite genomes is continuously
      enlarging the array of potential vaccine candidates and, additionally, the recent
      development of a transfection tool for Babesia can significantly contribute to
      vaccine design. However, the complication and high cost of vaccination trials
      hinder Babesia vaccine research, and have so far seriously limited the systematic
      examination of antigen candidates and prevented an in-depth testing of
      formulations using different immunomodulators and antigen delivery systems.

PMID- 25068316
TI  - Total synthesis of the purported structure of sclerophytin F.
AB  - The synthesis of the compound that has been proposed to be the natural product
      sclerophytin F has been completed from a known vinylogous carbonate. The
      synthetic strategy relied upon rearrangement of a catalytically generated ylide
      like intermediate to produce an oxabicyclo[6.2.1]-5-undecen-9-one and an
      intermolecular Diels-Alder reaction to construct the complete tricyclic core
      found in the natural product. Comparison of the spectroscopic data for synthetic
      material to that reported for sclerophytin F shows that the natural product does
      not have the revised structure possessing the 3S configuration (*) proposed
      previously. 

PMID- 25068318
TI  - An algorithmic approach for selective acellular dermal matrix use in immediate
      two-stage breast reconstruction: indications and outcomes.
AB  - BACKGROUND: Acellular dermal matrix use has gained widespread acceptance--despite
      higher material costs--because of its ease of use and potential for enhanced
      cosmesis. The authors developed a resource-sensitive algorithm for selective
      acellular dermal matrix use with indications and contraindications based on body
      mass index, breast size, radiation therapy, flap vascularity, and pectoralis
      anatomy. METHODS: The algorithm incorporates preoperative and intraoperative
      decision points. Complication rates and aesthetic scores were compared for
      procedures performed before and after adoption of the algorithm. Multiple
      logistic regression was used to determine the independent influence of the
      algorithm on postoperative outcomes. RESULTS: One hundred ninety-three breasts
      underwent reconstruction before and 179 underwent reconstruction after
      implementation of the algorithm. Overall complication rates did not differ
      between the cohorts (22.8 percent versus 20.7 percent; p=0.138). After adjusting
      for potential confounders, the algorithm did not significantly affect the
      incidence of infection, seroma, flap necrosis, explantation, or overall
      complications (all p>0.05). Aesthetic scores were not affected (2.75 of 4 versus
      3.03 of 4; p=0.138). Acellular dermal matrix use decreased from 84 percent to 36
      percent, resulting in a materials cost savings of $270,000 over the study period.
      CONCLUSIONS: This algorithm obviated placement of acellular dermal matrix in an
      estimated 48 percent of immediate tissue-expander reconstructions. Patients
      treated after adoption of this algorithm experienced similar complication rates
      and aesthetic outcomes as those who underwent reconstruction before. The authors'
      preliminary outcomes demonstrate that evidence-based measures can be taken to
      selectively use acellular dermal matrix without a concomitant worsening of
      patient outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 25068319
TI  - Discussion: An algorithmic approach for selective acellular dermal matrix use in
      immediate two-stage breast reconstruction: indications and outcomes.

PMID- 25068317
TI  - Blocking phosphatidylcholine utilization in Pseudomonas aeruginosa, via
      mutagenesis of fatty acid, glycerol and choline degradation pathways, confirms
      the importance of this nutrient source in vivo.
AB  - Pseudomonas aeruginosa can grow to very high-cell-density (HCD) during infection
      of the cystic fibrosis (CF) lung. Phosphatidylcholine (PC), the major component
      of lung surfactant, has been hypothesized to support HCD growth of P. aeruginosa
      in vivo. The phosphorylcholine headgroup, a glycerol molecule, and two long-chain
      fatty acids (FAs) are released by enzymatic cleavage of PC by bacterial
      phospholipase C and lipases. Three different bacterial pathways, the choline,
      glycerol, and fatty acid degradation pathways, are then involved in the
      degradation of these PC components. Here, we identified five potential FA
      degradation (Fad) related fadBA-operons (fadBA1-5, each encoding 3-hydroxyacyl
      CoA dehydrogenase and acyl-CoA thiolase). Through mutagenesis and growth
      analyses, we showed that three (fadBA145) of the five fadBA-operons are dominant
      in medium-chain and long-chain Fad. The triple fadBA145 mutant also showed
      reduced ability to degrade PC in vitro. We have previously shown that by
      partially blocking Fad, via mutagenesis of fadBA5 and fadDs, we could
      significantly reduce the ability of P. aeruginosa to replicate on FA and PC in
      vitro, as well as in the mouse lung. However, no studies have assessed the
      ability of mutants, defective in choline and/or glycerol degradation in
      conjunction with Fad, to grow on PC or in vivo. Hence, we constructed additional
      mutants (DeltafadBA145DeltaglpD, DeltafadBA145DeltabetAB, and
      DeltafadBA145DeltabetABDeltaglpD) significantly defective in the ability to
      degrade FA, choline, and glycerol and, therefore, PC. The analysis of these
      mutants in the BALB/c mouse lung infection model showed significant inability to
      utilize PC in vitro, resulted in decreased replication fitness and
      competitiveness in vivo compared to the complement strain, although there was
      little to no variation in typical virulence factor production (e.g., hemolysin,
      lipase, and protease levels). This further supports the hypothesis that lung
      surfactant PC serves as an important nutrient for P. aeruginosa during CF lung
      infection. 

PMID- 25068320
TI  - The ideal nasolabial angle in rhinoplasty: a preference analysis of the general
      population.
AB  - BACKGROUND: In aesthetic rhinoplasty, the described ideal nasolabial angle ranges
      from 90 to 120 degrees, with variable anthropologic differences. The authors
      sought to verify the most aesthetic nasolabial angle as specifically perceived by
      a random prospective sample of the general population and determine whether age,
      sex, race, and education were independent associated predictors. METHODS: The
      authors prospectively recruited 98 random volunteers from the general population.
      They were asked to rank three different nasolabial angles for the female nose
      (100, 105, and 110 degrees) and the male nose (90, 100, and 105 degrees) as
      "most," "moderately," and "least aesthetic." Demographic data were used to
      determine correlations between aesthetic preferences. Pearson chi-square test and
      t test were used to determine statistical significance RESULTS: The most
      aesthetic female nasolabial angle was 104.9+/-4.0 degrees. The most aesthetic
      male nasolabial angle was 97.0+/-6.3 degrees. Male subjects, younger volunteers,
      Native Americans, and African Americans preferred more acute male nasolabial
      angles (90 degrees). Female subjects, volunteers older than 50 years, college
      graduates, those with a previous rhinoplasty, and Caucasian and Asian subjects
      preferred more obtuse male nasolabial angles. CONCLUSIONS: In the authors' sample
      of the general population, the ideal and most aesthetic nasolabial angle ranged
      from 100.9 to 108.9 degrees in the female nose and 90.7 to 103.3 degrees in the
      male nose. Age, sex, race, education, and having undergone a previous rhinoplasty
      were predictors of differences in the ideal male nasolabial angle but did not
      change preference of the female nasolabial angle.

PMID- 25068321
TI  - Discussion: The ideal nasolabial angle in rhinoplasty: a preference analysis of
      the general population.

PMID- 25068322
TI  - The tissue-based triad: a process approach to augmentation mastopexy.
AB  - BACKGROUND: Among the most exigent operations in plastic surgery is the
      combination of augmentation and mastopexy. The surgical challenge is related to
      oppositional forces that complicate the operative predictability. The purpose of
      this study was to investigate use of the tissue-based triad process approach in
      patients undergoing augmentation mastopexy. Measured components of the approach
      include skin stretch, nipple to inframammary fold distance on maximal stretch,
      and vertical excess. METHODS: Patients were selected for the study if they had
      been treated with one- or two-stage augmentation mastopexy, or mastopexy alone.
      Data gathered included preoperative measurements, operative details,
      complications, and outcomes including reoperation rate. RESULTS: A total of 176
      consecutive patients were identified as meeting study inclusion criteria. Mean
      follow-up was 1.5 years. Seventy-one of 176 patients underwent mastopexy alone.
      Of the 176 patients included, 105 were treated with augmentation mastopexy.
      Ninety-one of 105 augmentation mastopexy operations were performed in one stage.
      The average amount of vertical excess was 5 cm. Nine patients exhibited delayed
      wound healing, while six (6.5 percent) required reoperations for scar revision
      (n=1), delayed wound healing requiring revision (n=2), hematoma (n=1), seroma
      (n=1), and soft-tissue stretch (n=1). Fourteen of 105 patients were treated in
      two stages. Average vertical excess was 7.5 cm. CONCLUSIONS: Use of the tissue
      based triad process approach provided objectivity in determining which patients
      should undergo one- versus two-stage augmentation mastopexy. Use of this approach
      helps guide surgical decision making and is associated with lower reoperation
      rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25068323
TI  - Improving fat transfer viability: the role of aging, body mass index, and harvest
      site.
AB  - BACKGROUND: Fat grafting remains unpredictable in the clinical setting, and
      variables that influence adipocyte survival, such as age, body mass index, and
      specific donor sites, are still not well understood. METHODS: Twenty-four female
      subjects were enrolled in this research after institutional review board approval
      and signed consent to participate was obtained. Subjects were separated into
      groups according to (1) age (younger, <=45 years; and older, >=46 years) and (2)
      body mass index (normal weight, body mass index<25; and overweight, body mass
      index>=25). All fat samples were obtained through dry liposuction of three donor
      sites: lower abdomen, inner thigh, and flank. They were processed identically for
      dissociation of adipose tissue and isolation of adipocytes. Adipocyte viability
      was measured using the Nexcelom Cellometer Auto T4. RESULTS: In younger patients,
      adipocyte viability was greater in the lower abdomen than in the flank; in older
      patients, this difference was not seen. When lower abdominal fat from younger was
      compared with that from older patients, the viability was higher in younger
      patients. However, adipocytes from the flank depot had higher viability in the
      older group compared with the younger group. Inner thigh fat viability was not
      significantly different across the two age groups. The authors also found no
      significant differences in fat viability for any given donor site between the
      normal weight and overweight body mass index groups. CONCLUSIONS: The optimal
      choice site for fat harvest should take patient age into consideration. In
      younger patients, both lower abdomen and inner thigh appear to be good options.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 25068324
TI  - Perceived realism and Twitter use are associated with increased acceptance of
      cosmetic surgery among those watching reality television cosmetic surgery
      programs.
AB  - BACKGROUND: Reality television programming is a popular type of television
      programming, and features shows about cosmetic surgery. Social media such as
      Facebook and Twitter are increasingly popular methods of sharing information. The
      authors surveyed college students to determine among those watching reality
      television cosmetic surgery programs whether perceived realism or social media
      use was associated with attitudes toward cosmetic surgery. METHODS: Participants
      (n=126) were surveyed about their reality television cosmetic surgery program
      viewing habits, their perception of the realism of reality television
      programming, and social media topics of Twitter and Facebook. Outcome variables
      were the Acceptance of Cosmetic Surgery Scales of social, intrapersonal, and
      consider. RESULTS: Perceived realism was significantly associated with increased
      scores on the Acceptance of Cosmetic Surgery Scale subscales of social (p=0.004),
      intrapersonal (p=0.03), and consider (p=0.03). Following a character from a
      reality television program on Twitter was significantly associated with increased
      social scores (p=0.04). There was no significant association of Facebook behavior
      with attitudes toward cosmetic surgery. CONCLUSIONS: Cosmetic plastic surgeons
      may benefit by advertising their services on cosmetic surgery reality television
      programs. These reality television programs portray cosmetic surgery in a
      positive manner, and viewers with increased perceived realism will be a potential
      receptive audience toward such advertising. Also, advertising cosmetic surgery
      services on Twitter feeds that discuss cosmetic surgery reality television
      programs would be potentially beneficial.

PMID- 25068326
TI  - Subungual melanoma: a review of current treatment.
AB  - BACKGROUND: Subungual melanoma typically presents as a darkened longitudinal
      stripe under the nail plate; however, this disease is frequently misdiagnosed,
      which leads to a delay in proper diagnosis. Subsequently, subungual melanoma
      historically has a relatively poor prognosis compared with other cutaneous
      melanomas, with the 5-year survival rate ranging between 16 and 80 percent.
      Historically, these lesions were removed using aggressive amputation. To date,
      the National Cancer Institute does not have guidelines for the treatment of
      subungual melanoma. METHODS: The authors conducted a complete review of all cases
      within the literature involving amputation and/or wide local excision for the
      treatment of subungual melanoma. RESULTS: There is currently a trend toward a
      more conservative approach in treating subungual melanoma; however, the
      literature does not offer a high level of evidence, and definitive conclusions
      cannot be drawn. CONCLUSIONS: Overall, the studies within the literature
      involving amputation as the treatment for subungual melanoma could not prove a
      significant benefit, in terms of prognosis and/or survival, over the more
      conservative treatment of excision. The collective data imply that melanoma in
      situ can likely be treated appropriately with wide local excision. The literature
      lacks randomized, prospective, or comparative studies that would help elucidate
      whether amputation is superior to a more conservative, digit-sparing approach.
      Prospective randomized control trials are indicated.

PMID- 25068325
TI  - Studies in fat grafting: Part III. Fat grafting irradiated tissue--improved skin
      quality and decreased fat graft retention.
AB  - BACKGROUND: Following radiation therapy, skin becomes fibrotic and can present a
      difficult problem for reconstructive surgeons. There is an increasing belief that
      fat grafting under irradiated skin can reverse the damage caused by radiation.
      The present study evaluated the effect of fat grafting on irradiated skin, along
      with fat graft quality and retention rates in irradiated tissue. METHODS: Nine
      adult Crl:NU-Foxn1 CD-1 mice underwent 30-Gy external beam irradiation of the
      scalp. Four weeks after irradiation, scalp skin from irradiated and nonirradiated
      mice was harvested and compared histologically for dermal thickness, collagen
      content, and vascular density. Human fat grafts were then injected in the
      subcutaneous plane of the scalp. Skin assessment was performed in the irradiated
      group at 2 and 8 weeks after grafting, and fat graft retention was measured at
      baseline and every 2 weeks up to 8 weeks after grafting using micro-computed
      tomography. Finally, fat graft samples were explanted at 8 weeks, and quality
      scoring was performed. RESULTS: Fat grafting resulted in decreased dermal
      thickness, decreased collagen content, and increased vascular density in
      irradiated skin. Computed tomographic analysis revealed significantly decreased
      fat graft survival in the irradiated group compared with the nonirradiated group.
      Histologic scoring of explanted fat grafts demonstrated no difference in quality
      between the irradiated and nonirradiated groups. CONCLUSIONS: Fat grafting
      attenuates dermal collagen deposition and vessel depletion characteristic of
      radiation fibrosis. Although fat graft retention rates are significantly lower in
      irradiated than in nonirradiated tissue, the quality of retained fat between the
      groups is similar.

PMID- 25068327
TI  - Analysis of midface retrusion in Crouzon and Apert syndromes.
AB  - BACKGROUND: Midface retrusion is the hallmark of the syndromic dysostoses (i.e.,
      Crouzon and Apert). Lack of forward projection and/or structural deficiency could
      be responsible, but neither has been adequately assessed three-dimensionally. The
      authors examined both the cranial base/facial interface and the midface volume to
      provide an understanding of the etiopathogenesis of midface deficiency. METHODS:
      Children with computed tomographic scans in the absence of any surgical
      intervention were included. Demographic information was recorded for three
      groups: Apert, Crouzon, and control. Scans were digitized and manipulated using
      Materialise software (Surgicase CMF). Craniometric data relating to the midface
      and sphenoid were collected. Volumetric assessment of the midface was tabulated.
      Statistical analysis was performed using the t test. RESULTS: Thirty-six scans
      were included (control, n=17; Crouzon/Apert, n=19). All children were in the
      early mixed dentition stage. The anterior cranial fossa proved to be shorter and
      wider in Crouzon/Apert patients compared with controls. The cranial base angles
      (N-S-BA, N-S-SO, N-SO-BA, S-SO-BA, and N-S-AR) were not statistically different
      across the groups. The Crouzon/Apert group showed angles more obtuse between the
      greater wings of the sphenoid, and more obtuse (more splayed) between the
      pterygoid plates. Nasion-sella-pterygomaxillary fissure angle was more obtuse
      (flatter) in the Crouzon/Apert group. There was no volumetric difference in the
      maxilla, zygoma, and sphenoid comparing the Crouzon/Apert group to controls.
      CONCLUSIONS: Midface retrusion in the Crouzon/Apert group is associated with
      altered sphenoid morphology (widened and retruded pterygoid plates), with a
      flatter and wider maxilla, suggesting diminished growth inferiorly and
      anteriorly. There is no volumetric deficiency in Crouzon/Apert patients compared
      with controls. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 25068329
TI  - Discussion: Primary correction of nasal asymmetry in patients with unilateral
      coronal synostosis.

PMID- 25068328
TI  - Primary correction of nasal asymmetry in patients with unilateral coronal
      synostosis.
AB  - BACKGROUND: The optimal strategy for correction of significant nasal angulation
      in patients with unilateral coronal synostosis remains controversial. The authors
      report a novel technique for correction of significant nasal angulation in these
      patients, in which dissection of the nasal bones is limited to the site of the
      osteotomy, maintaining continuity with the soft-tissue envelope and the nasal
      cartilages. METHODS: Seven successive patients with unilateral coronal synostosis
      and nasal deviation of greater than 6 degrees by computed tomographic analysis
      were evaluated. Three patients were treated using ex vivo repositioning in which
      the nasal bones were freed completely from the surrounding soft-tissue envelope,
      and four patients were treated with in vivo repositioning by performing a
      subperiosteal dissection only where required for lateral nasal osteotomies
      without separating the nasal bones from the cartilaginous framework of the nose.
      Nasal angulation was calculated using clinical photographs and three-dimensional
      computed tomography preoperatively and at 1-year follow-up. RESULTS: Mean nasal
      angulation was reduced from 9.5 degrees to 2.5 degrees by computed tomographic
      analysis (p<0.001) and from 6.9 degrees to 1.9 degrees by photographic analysis
      (p<0.01) 1 year postoperatively. There was no significant difference in outcome
      between patients who underwent ex vivo or in vivo repositioning. CONCLUSIONS:
      Primary surgical correction of significant nasal angulation in patients with
      unilateral coronal synostosis can be achieved with less dissection and disruption
      of soft-tissue relationships than previously described without compromise in
      efficacy. The authors' technique for osteotomy of the nasal bones preserves nasal
      architecture, minimizes periosteal dissection, and may theoretically reduce the
      potential for growth disruption. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 25068330
TI  - Comparison of vertical and oblique rectus abdominis myocutaneous flaps for
      pelvic, perineal, and groin reconstruction.
AB  - BACKGROUND: Wound complications after perineal and groin obliterative procedures
      are a significant cause of morbidity, particularly following chemoradiation
      therapy. Vertical and, increasingly, oblique rectus abdominis myocutaneous flaps
      have been used to fill potential dead space and bring healthy, vascularized
      tissue into the defect. The authors compared the complications and outcomes of
      patients undergoing perineal or groin reconstruction with vertical or oblique
      rectus abdominis myocutaneous flaps. They hypothesized that the oblique flap
      offers outcomes similar to those of the vertical flap, without an increased risk
      of complications. METHODS: All patients who underwent immediate reconstruction of
      perineal, pelvic, or groin defects using vertical (n=49) or oblique rectus
      abdominis myocutaneous (n=22) flaps over the past 10 years at the University of
      Washington Medical Center were reviewed retrospectively. Patient, disease, and
      obliterative procedure characteristics and donor- and recipient-site
      complications were compared. Statistical analysis was performed using the t test
      for continuous variables and Fisher's exact test for categorical variables.
      RESULTS: There were no statistically significant differences in major or minor
      donor- or recipient-site complication rates, need for augmented fascial closure,
      need for additional flaps, flap loss, readmission, or reoperation rate between
      the two groups. CONCLUSIONS: Immediate reconstruction of perineal or groin
      defects with oblique rectus abdominis myocutaneous flaps results in complication
      rates similar to those with reconstruction using with vertical flaps. Oblique
      flap reconstruction is a reasonable and safe alternative, providing several
      distinct advantages over the vertical flap, including greater arc of rotation,
      thinner skin paddle, less bulk, and limited fascial harvest. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 25068331
TI  - Multiple limbs salvaged using tissue transfers in the same casualty: a cohort
      comparison study chronicling a decade of war-injured patients.
AB  - BACKGROUND: Extremity battlefield injuries from Operation Iraq and Enduring
      Freedom (Afghanistan) requiring multiple limbs salvaged with tissue transfers in
      the same patient are an understudied population. This study aimed to report the
      limb salvage outcomes in patients requiring multiple flap procedures for two or
      more concurrent extremity injuries. METHODS: A retrospective cohort comparison of
      warfare-related extremity injuries treated for limb salvage from 2003 through
      2012 at the National Capital Consortium was completed. Number of single and
      multiple flap limb salvages, Injury Severity Score, success rates, and
      complications were analyzed. RESULTS: A total of 359 limb salvage reconstructive
      procedures were performed, consisting of 311 cases of single extremity salvage
      and 48 cases of multiple flap or multiple extremity salvage. The Injury Severity
      Score was significantly higher in the multiple extremity group (23) than in the
      single extremity group (17; p<0.001). Primary flap failure rate was 9 percent in
      single and 12 percent in multiple limb salvage cases (p=0.390). The subgroup flap
      failure rate in the multiple limb salvage cohort was 8 percent, 7 percent, and 25
      percent for pedicle flaps, pedicle/free flaps, and free flaps, respectively
      (p=0.361). The total complication rate was 26 percent and 33 percent for single
      and multiple limb salvage cases, respectively (p=0.211). CONCLUSION: Limb salvage
      requiring multiple flap procedures in the polyextremity-injured patent is safe
      and equally effective when compared with a single-limb-injured cohort despite a
      significantly higher injury severity score. Overall complication rates were not
      significantly different, although subgroup analysis demonstrated a trend toward
      increased flap failure in the multiple free flap cohort. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, III.

PMID- 25068332
TI  - Young Plastic Surgeons Forum member survey: Part I. Investing in the future:
      attitudes toward the Plastic Surgery Foundation.
AB  - BACKGROUND: Professional and social changes have resulted in decreased
      involvement in organizations. Little is currently known about young plastic
      surgeons' attitudes toward the Plastic Surgery Foundation and its sponsored
      activities. The authors gathered opinions of young plastic surgeons to determine
      factors related to participation. METHODS: A 21-question online survey was e
      mailed to all 2155 members of the Young Plastic Surgeons Forum. Questions were
      related to demographics, current involvement, and initiatives in education,
      research, funding, and health policy. RESULTS: Of 2155 forum members, 397
      responded (19 percent response rate). Most had not contributed to the Plastic
      Surgery Foundation. The primary reason cited was financial hardship, and
      respondents noted this would change with increased practice revenue. Involvement
      in American Society of Plastic Surgeons committees correlated with contribution
      to Plastic Surgery Foundation. The main educational initiatives favored by Young
      Plastic Surgeons included critical analysis of literature/evidence-based
      medicine, statistical analysis, and compensation issues. According to
      respondents, primary areas for organizational focus should be clinical research,
      increased representation of young surgeons, and leadership development.
      Respondents would be more willing to donate if they could earmark their
      contributions for specific purposes, including leadership training, clinical
      research, and medical missions. CONCLUSIONS: Methods to recruit and retain young
      surgeons into the American Society of Plastic Surgeons and in contributing to the
      Plastic Surgery Foundation should include opportunities to participate at a
      decreased cost, focus on compensation issues, clinical research, leadership
      development, and increased young surgeon representation. These data should be
      used to guide efforts to increase young member involvement.

PMID- 25068333
TI  - Discussion: Young Plastic Surgeons Forum member survey: Part I. Investing in the
      future: attitudes toward the Plastic Surgery Foundation.

PMID- 25068334
TI  - Young Plastic Surgeons Forum member survey: Part II. Advocacy in plastic surgery:
      opinions toward the ASPS and PlastyPAC.
AB  - BACKGROUND: Given the continued evolution of the American health system, the
      authors explored young plastic surgeons' attitudes on challenges affecting the
      specialty and the future role of organized plastic surgery and its advocacy
      mission. METHODS: A 21-question online survey was distributed to all members of
      the Young Plastic Surgeons Forum. Questions were related to demographics,
      attitudes toward policy issues, participation in the American Society of Plastic
      Surgeons, and its advocacy efforts. RESULTS: The survey was e-mailed to 2155
      Forum members, of which 397 responded (19% response rate). Young plastic surgeons
      appear to be interested in American Society of Plastic Surgeons and PlastyPAC, as
      evidenced by a higher than normal response rate to this survey and rate of
      contribution. However, a lack of awareness about the details of the organizations
      and mechanisms for involvement remains. Scope-of-practice issues and encroachment
      on the specialty by noncore providers remain the top concern of young plastic
      surgeons. Other top concerns were financial barriers to participation in advocacy
      efforts and concerns with return on investment on PlastyPAC contributions. A
      majority received minimal or no public policy education on issues affecting
      plastic surgery during training. A minority currently participate in American
      Society of Plastic Surgeons advocacy efforts. CONCLUSIONS: These data represent
      the first such collection of opinions from Young Plastic Surgeons members
      regarding goals and directions of the American Society of Plastic Surgeons and
      PlastyPAC. These organizations are in a uniquely strong position to enlist
      participation from and provide for the future success of the profession's younger
      members.

PMID- 25068335
TI  - Discussion: Young Plastic Surgeons Forum member survey: Part II. Advocacy in
      plastic surgery: opinions toward the ASPS and PlastyPAC.

PMID- 25068336
TI  - Discussion: Young Plastic Surgeons Forum member survey: Part II. Advocacy in
      plastic surgery: opinions toward the ASPS and PlastyPAC.

PMID- 25068339
TI  - A detailed evaluation of the anatomical variations of the profunda artery
      perforator flap using computed tomographic angiograms.
AB  - BACKGROUND: The profunda artery perforator flap is a new option for breast
      reconstruction in appropriate patients. While the basic anatomy is known,
      detailed profunda perforator anatomy has never fully been described and we
      present new data that will aid dissection. METHODS: Fifty consecutive lower
      extremity computed tomography angiogram scans (100 legs) were retrospectively
      analyzed to acquire profunda artery perforator measurements. Patient medical
      records were then examined to ascertain patient information. Data were then
      analyzed using simple descriptive statistics and bivariate linear regressions
      with repeated measures. RESULTS: Bilateral thighs from 50 consecutive angiograms
      were included for a total of 100 thighs. Females comprised 30 (60 percent) of the
      patients and the cohort average age was 59.1 years old. All thighs had at least
      two perforators, with 85 percent having three or more. On average, perforators
      were located 6.2 cm below the gluteal crease, and were evenly distributed between
      the medial and lateral halves of the thigh. The average perforator diameter at
      origin off profunda was 2.7 mm. There was significantly greater diameter in
      vessels in the lateral thigh (p<0.001), in patients with higher Body Mass Index
      (BMI) (p<0.05), and in patients with decreased age (p<0.05). Males were more
      likely to have perforators that shared a common trunk off the profunda artery
      (p<0.05). CONCLUSIONS: At least two profunda perforators exist in each thigh with
      an average diameter suitable for microvascular transfer, although larger
      perforators are observed laterally and in younger patients with higher BMI.

PMID- 25068340
TI  - Risk of readmission following immediate breast reconstruction: results from the
      2011 American College of Surgeons National Surgical Quality Improvement Program
      data sets.
AB  - BACKGROUND: With health reform increasingly focused on readmission rates as an
      indicator of quality of care, providers have a duty to identify patients at risk
      of readmission. The authors assessed the incidence and risk factors for
      readmission following immediate breast reconstruction. METHODS: Patients who
      underwent immediate breast reconstruction were identified through the 2011
      American College of Surgeons National Surgical Quality Improvement Program
      database. Patients were grouped by readmission or no readmission and analyzed for
      trends in comorbidities and intraoperative characteristics. A multivariate
      regression analysis was performed to identify independently associated predictors
      of readmission. RESULTS: Overall, 3097 patients underwent immediate breast
      reconstruction; 5.8 percent were readmitted within 30 days of discharge.
      Readmitted patients had significantly higher body mass index [28.7 (6.6) versus
      27.0 (6.5) kg/m2; p=0.005], were more likely to be smokers (17.2 percent versus
      11.7 percent; p=0.03), and were more likely to have comorbid conditions (37.2
      percent versus 26.1 percent; p=0.005). Readmitted patients were more likely to
      experience surgical complications as inpatients (1.7 percent versus 0.3 percent;
      p=0.02) or outpatients (40.6 percent versus 2.6 percent; p<0.001). On
      multivariate regression analysis, readmission was associated with smoking
      (OR=1.60; p=0.027) and obesity (OR=1.62; p=0.004), while total length of stay and
      inpatient surgical complications neared significance. CONCLUSIONS: Patients
      undergoing immediate breast reconstruction should be identified and risk
      stratified appropriately if they are obese, smokers with extended length of stay,
      or have surgical complications. Early identification may reduce the impact of
      readmission on the patient or minimize the likelihood of readmission altogether,
      whether via greater scrutiny before discharge or frequent postdischarge follow
      up. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 25068341
TI  - Nipple-sparing mastectomy in patients with prior breast irradiation: are patients
      at higher risk for reconstructive complications?
AB  - BACKGROUND: Reconstruction in the setting of prior breast irradiation is
      conventionally considered a higher-risk procedure. Limited data exist regarding
      nipple-sparing mastectomy in irradiated breasts, a higher-risk procedure in
      higher-risk patients. METHODS: The authors identified and reviewed the records of
      501 nipple-sparing mastectomy breasts at their institution from 2006 to 2013.
      RESULTS: Of 501 nipple-sparing mastectomy breasts, 26 were irradiated. The
      average time between radiation and mastectomy was 12 years. Reconstruction
      methods in the 26 breasts included tissue expander (n=14), microvascular free
      flap (n=8), direct implant (n=2), latissimus dorsi flap with implant (n=1), and
      rotational perforator flap (n=1). Rate of return to the operating room for
      mastectomy flap necrosis was 11.5 percent (three of 26). Nipple-areola complex
      complications included one complete necrosis (3.8 percent) and one partial
      necrosis (3.8 percent). Complications were compared between this subset of
      previously irradiated patients and the larger nipple-sparing mastectomy cohort.
      There was no significant difference in body mass index, but the irradiated group
      was significantly older (51 years versus 47.2 years; p=0.05). There was no
      statistically significant difference with regard to mastectomy flap necrosis
      (p=0.46), partial nipple-areola complex necrosis (p=1.00), complete nipple-areola
      complex necrosis (p=0.47), implant explantation (p=0.06), hematoma (p=1.00),
      seroma (p=1.00), or capsular contracture (p=1.00). CONCLUSION: In the largest
      study to date of nipple-sparing mastectomy in irradiated breasts, the authors
      demonstrate that implant-based and autologous reconstruction can be performed
      with complications comparable to those of the rest of their nipple-sparing
      mastectomy patients.

PMID- 25068342
TI  - Discussion: Nipple-sparing mastectomy in patients with prior breast irradiation:
      are patients at higher risk for reconstructive complications?

PMID- 25068343
TI  - Classification of masseter hypertrophy for tailored botulinum toxin type A
      treatment.
AB  - BACKGROUND: Botulinum toxin type A has been increasingly used to improve the
      lower face contour in masseter hypertrophy. Different dosages and injection
      techniques are suggested in the literature, but the ideal approach remains
      unclear. This study aimed to establish an objective masseter classification
      method for a personalized botulinum toxin type A injection protocol. METHODS: A
      combination of clinical palpation, B-mode ultrasound examination, and anatomical
      dissection studies was applied to classify the masseter regarding bulging type on
      clenching and muscle thickness in a normal population and in patients desiring
      reduction of masseter hypertrophy. Based on these findings, a tailored botulinum
      toxin type A injection protocol was set up and evaluated in a prospective
      clinical study regarding masseter thickness, facial measurements, patient
      satisfaction, and complications. RESULTS: A total of 504 masseters were
      classified into five bulging types (minimal, mono, double, triple, and excessive)
      and three degrees of thickness (<10 mm, 10 to 14 mm, and >14 mm). Two hundred
      twenty cases were treated using individualized botulinum toxin type A injection
      dosages (20 to 40 units) and sites (one to three per muscle); the treatment was
      applied in 220 cases, according to the respective classification. Masseter
      thickness decreased significantly, from 12.9+/-2.9 mm to 8.7+/-1.7 mm, 3 months
      after injection (p<0.01). The initial ratio of the widest width of the lower face
      to the intercanthal distance (3.3+/-0.18) was also significantly reduced (3.0+/
      0.2; p<0.01). The overall patient satisfaction rate was 95.9 percent. No serious
      complications occurred.. CONCLUSIONS: The present study provides the scientific
      basis for individualized botulinum toxin type A injection for masseter
      hypertrophy. This protocol allowed for reduction of injection dosage and
      complication rates, and showed beneficial clinical effects in terms of
      significantly reduced masseter volume and improved lower face contour. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25068344
TI  - Double-blind clinical trial to compare autologous fat grafts versus autologous
      fat grafts with PDGF: no effect of PDGF.
AB  - BACKGROUND: This work evaluates the effect of adding platelet-derived growth
      factor to autologous adipose tissue grafts in the treatment of human
      immunodeficiency virus facial lipoatrophy by means of objective measurements.
      METHODS: This is a randomized clinical trial conducted at the Hospital Clinic of
      Barcelona. Patients with facial human immunodeficiency virus atrophy were
      randomized into two groups, one treated with autologous fat injection (group A),
      and another treated with autologous fat injection with plasma rich in growth
      factors (group B). Before the treatment, structural changes were identified in
      facial soft tissue by means of computed tomography, and clinical changes were
      also assessed by means of photographic records. Posttreatment assessments were
      repeated after 2 and 12 months to compare the results. Posttreatment
      complications were recorded. RESULTS: Forty-nine patients (33 men and 16 women),
      with a mean age of 46 years, participated in the study. In both groups, there was
      a statistically significant average increase of volume in the facial area
      measured by computed tomography between the baseline and the 2- and 12-month
      posttreatment assessments. All cases showed an improvement of the clinical facial
      atrophy grade after treatment, which was statistically significant. This
      improvement was related to a statistically significant fat volume increase
      measured by means of computed tomography. There was no difference in the volume
      gain between both groups. No major complications were observed. CONCLUSIONS: Fat
      grafting is a safe, effective, and durable treatment for human immunodeficiency
      virus facial atrophy. The results of this study show that it is not necessary to
      add plasma rich in growth factors to the adipose tissue graft to get a better
      result. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 25068345
TI  - Angiogenin: a potential serum marker of infantile hemangioma revealed by cDNA
      microarray analysis.
AB  - BACKGROUND: Hemangiomas are characterized by rapid growth but slow regression.
      Prognosis and treatment urgently require the identification of serum markers to
      determine the proliferative potential of hemangiomas. METHODS: Using four pairs
      of tissue from the proliferative and involution stages of the same hemangiomas,
      the authors performed cDNA microarray experiments to study differential
      expression of genes between proliferative hemangiomas and involuting hemangiomas.
      Among these genes, the authors searched for possible serum markers. A novel
      analysis process was used to screen for up-regulated genes encoding secreted
      proteins. Next, the mRNA and protein expression in hemangiomas and serum levels
      in patients with hemangiomas were validated by quantitative reverse-transcriptase
      polymerase chain reaction, immunohistochemistry, Western blotting, and enzyme
      linked immunosorbent assay. RESULTS: Sixty-two up-regulated genes were detected
      in proliferative hemangiomas. Angiogenin, a key angiogenesis factor induced by
      hypoxia, was found to be a possible serum marker. Angiogenin mRNA and protein
      expression were validated by quantitative reverse-transcriptase polymerase chain
      reaction, immunohistochemistry, and Western blotting. An enzyme-linked
      immunosorbent assay confirmed that angiogenin serum levels correlate with the
      hemangioma stage. Moreover, receiver operating characteristic curve analysis
      indicates a high sensitivity and specificity of angiogenin for discriminating
      between proliferative hemangiomas and the control group and patients with venous
      malformations. CONCLUSIONS: The authors report for the first time that angiogenin
      may be a useful serum marker for hemangiomas, and report a novel analysis process
      that might efficiently screen for potential serum markers of tumors by cDNA
      microarray analysis.

PMID- 25068346
TI  - Early prediction of skin viability using visible diffuse reflectance spectroscopy
      and autofluorescence spectroscopy.
AB  - BACKGROUND: Accurate and early prediction of skin flap viability is vitally
      important in reconstructive surgery. To the best of the authors' knowledge, this
      is the first pilot study to evaluate the simultaneous use of both visible diffuse
      reflectance and autofluorescence spectroscopy on a reverse MacFarlane rat dorsal
      skin flap model in the early prediction of skin viability. METHODS: A total of 62
      flap measurement sites from 11 Sprague-Dawley rats were monitored for 72 hours.
      Both statistical analysis using measured spectra and quantification of
      physiologically relevant tissue parameters using empirical methods were
      performed. RESULTS: The statistical analysis results suggest that either visible
      diffuse reflectance spectroscopy or autofluorescence spectroscopy alone can
      predict the skin viability accurately; however, autofluorescence spectroscopy is
      more sensitive to tissue changes in the first 2 hours after induction of
      ischemia. The pilot study shows that it is feasible to predict flap failures in
      the first 2 hours when using autofluorescence spectroscopy alone; moreover, it is
      possible to predict flap failures even in the first 15 minutes with high accuracy
      when using diffuse reflectance and autofluorescence spectroscopy simultaneously.
      Meanwhile, several physiologically relevant parameters including hemoglobin
      oxygenation, total hemoglobin concentration, and redox ratio indicators estimated
      from diffuse reflectance and autofluorescence spectra show distinctively
      different trends over time for nonviable and viable skin. CONCLUSIONS: These
      findings will be helpful to clinicians for making a precise judgment on flap
      viability. Furthermore, the authors' results highlight the advantage of using
      autofluorescence spectroscopy in the early prediction of skin flap viability
      relative to diffuse reflectance spectroscopy.

PMID- 25068347
TI  - A highly infectious chimeric adenovirus expressing basic fibroblast growth factor
      exerts potent targeted therapy for rabbit ear chronic ischemic wounds.
AB  - BACKGROUND: Poor angiogenesis and impaired proliferation of cells responsible for
      the repair of chronic ischemic wounds result in impaired wound healing. The
      continuous and efficient expression of therapeutic factors by means of gene
      transfection is an ideal adjuvant treatment method to promote cell proliferation
      and angiogenesis. METHODS: A chimeric recombinant adenoviral vector, Ad5F35ET1
      bFGF, was constructed that carried the basic fibroblast growth factor (bFGF) gene
      and used the endothelin-1 promoter to control the targeted expression of bFGF in
      endothelial cells and fibroblasts. Thus, the authors established a targeted gene
      therapy for chronic ischemic wounds. RESULTS: The chimeric adenovirus Ad5F35ET1
      bFGF efficiently infected the endothelin-1-positive endothelial cells and
      fibroblasts, specifically expressed bFGF, and promoted cell proliferation. In the
      rabbit wound healing model, the chimeric recombinant adenovirus expressed a high
      level of bFGF in wound tissues, which continuously promoted angiogenesis and cell
      proliferation and thus accelerated wound healing. CONCLUSION: Targeted gene
      therapy that uses bFGF as a therapeutic gene provides an effective candidate
      strategy for the treatment of chronic ischemic wounds.

PMID- 25068348
TI  - Patient risk factors for ambulatory cleft lip repair: an outcome and cost
      analysis.
AB  - BACKGROUND: The purpose of this study was to identify variables that may
      preoperatively predict successful outcomes in ambulatory cleft lip repair and to
      quantify the potential cost savings. METHODS: A retrospective chart review of all
      patients who underwent cleft lip repair at a tertiary cleft care center from
      January of 2010 to May of 2013 was performed. Because inpatient stay is the
      authors' current practice, overnight desaturations, poor oral intake, and failure
      to stop intravenous narcotics during the first day were considered indicators of
      a poor candidate. Charge data were also collected. RESULTS: Twenty-nine of 111
      patients were deemed likely to fail ambulatory surgery. American Society of
      Anesthesiologists score greater than 2 (p=0.019), low birth weight (p=0.022),
      bilateral cleft lip-cleft palate (p=0.003), central nervous system or neurologic
      diagnosis (p=0.046), syndromic and/or multiple congenital abnormalities
      (p=0.024), prior emergency room visits (p=0.021), failure to thrive (p=0.046),
      and age older than 7 months (p=0.028) were associated with poor candidacy. A
      diagnosis of cleft lip was protective (p=0.015). Fifty-five patients had no risk
      factors for a poor ambulatory outcome and did not stay more than 1 day. The
      average savings per patient who met the authors' criteria was $4261. CONCLUSIONS:
      The authors found that 49.5 percent of children may be safely eligible for
      ambulatory cleft lip repair. Patients with risk factors may be best served by a
      short hospital admission. This would lead to a national savings of $8,765,183 per
      year.

PMID- 25068349
TI  - Adopted children with cleft lip and/or palate: a unique and growing population.
AB  - BACKGROUND: Standard clinical pathways are well established for children with
      cleft lip and/or palate. Treatment of internationally adopted children differs
      because of the late age at presentation, a newly evolving child-family
      relationship, and variable extent and quality of previous treatment. METHODS: The
      authors characterized the presentation and treatment patterns of all
      internationally adopted children with clefts at their institution between 1997
      and 2011. RESULTS: Among 1841 children with clefts, 216 (12 percent) were
      internationally adopted: 78 percent had cleft lip and palate, 18 percent had
      cleft lip, and 4 percent had cleft palate. Patients originated predominantly from
      China (80 percent). Median age at presentation was 31 months, and the rate of new
      presentations increased five-fold during the study period. Eighty-two percent
      presented with prior cheiloplasty, and revision was recommended for 64 percent of
      them. Thirty-seven percent of patients had prior palatoplasty, of which 34
      percent presented with a palatal fistula. Secondary palatoplasty/pharyngoplasty
      was performed more frequently for patients who underwent primary palatoplasty
      before adoption than after adoption (95 percent CI, 0.20 to 0.77). Overall,
      adoptees required secondary surgery more often than nonadoptees (49 percent
      versus 28 percent) regardless of where their primary surgery was performed.
      Changes in adoptee growth indices suggested improvements in systemic health
      following adoption. CONCLUSIONS: Internationally adopted children with clefts
      have unique treatment challenges. Children with unrepaired clefts undergo surgery
      late, and children with prior repairs frequently undergo revision. Compared with
      nonadoptees, adoptees require more revisions and have a higher fistula rate.
      Further detailed study is important to optimize care.

PMID- 25068350
TI  - Restoring tactile and erogenous penile sensation in low-spinal-lesion patients:
      procedural and technical aspects following 43 TOMAX nerve transfer procedures.
AB  - BACKGROUND: The "TOMAX" (TO MAX-imize sensation, sexuality, and quality of life)
      procedure restores genital sensation in men with low spinal lesions, improving
      sexual health, as shown previously. It connects the dorsal nerve of the penis to
      the intact ipsilateral ilioinguinal nerve, unilaterally or bilaterally. This
      study reports on the technical aspects based on 43 TOMAX nerve transfers.
      METHODS: In 40 patients with no penile but intact groin sensation, 43 nerve
      transfers were performed. Data on patient selection, surgical history, anatomy of
      the ilioinguinal nerve and dorsal nerve of the penis, unilateral or bilateral
      surgery, surgical technique, complications, and patient information were
      collected prospectively. RESULTS: Regardless of origin, all patients with no
      penile but good groin sensation are eligible for the procedure, provided the
      ilioinguinal nerve is not damaged because of former inguinal surgery or absent
      because of anatomical variations. Selection of a unilateral or bilateral
      procedure depends on the presence or absence of reflex erections and
      bulbocavernosus reflex. Preliminary experience with the first three bilateral
      cases shows that it is technically feasible, with encouraging results. The
      surgical technique has evolved (described in detail, including video) to enhance
      outcome and reduce complications. Patients are better informed, resulting in
      realistic expectations. CONCLUSIONS: This article synthesizes the procedural and
      technical experience of 43 TOMAX nerve transfers. Anyone skilled in peripheral
      nerve surgery and microsurgery can adopt this concept and further develop it. The
      TOMAX procedure can then be used to restore erogenous penile sensation and
      improve the quality of sexual health in patients with absent penile but good
      groin sensation.

PMID- 25068351
TI  - An evidence-based structured review to assess the results of common peroneal
      nerve repair.
AB  - BACKGROUND: When is common peroneal nerve repair worthwhile? What is the effect
      of delayed repair? What is the maximum length of graft that can be used? This
      study aimed to address these questions by assessing the current literature and
      ascertaining the predictors of outcome that would guide peripheral nerve surgeons
      in determining the correct treatment of common peroneal nerve injury. METHODS:
      After an extensive literature review, 28 studies (1577 repairs) were assessed.
      The authors evaluated outcomes, using the British Medical Research Council
      grading for motor recovery, where M4 or above was considered a good outcome, and
      related them to delay, graft length, mechanism of injury, and age. RESULTS: Good
      outcomes (M4 and M5) were obtained in 45 percent of cases; more specifically, 80
      percent for neurolysis, 37 percent for direct suture, and 36 percent for nerve
      graft. Excluding neurolysis, good outcomes were obtained in 44 percent of repairs
      performed within 6 months but in only 12 percent of repairs performed after 12
      months (p=0.0046), and in 64 percent of repairs using grafts shorter than 6 cm
      but in only 11 percent of repairs using grafts longer than 12 cm (p=0.0002). Age
      did not influence outcome (p=0.2750). CONCLUSIONS: Common peroneal nerve repair
      was worthwhile in approximately half of all cases. The authors suggest that the
      results of common peroneal nerve repair will be suboptimal if surgery is
      performed more than 12 months after injury or if a graft of more than 12 cm is
      required.

PMID- 25068352
TI  - Wrist essentials: the diagnosis and management of scapholunate ligament injuries.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the pathophysiology of a scapholunate injury. 2. Understand how
      to diagnose scapholunate injuries 3. Formulate and carry out a surgical plan for
      patients with a scapholunate injury. SUMMARY: Scapholunate ligament instability
      is the most common form of carpal instability. Untreated scapholunate injuries
      can lead to a predictable pattern of wrist arthritis. Early forms of scapholunate
      ligament instability can be missed, and clinical detection relies on an educated
      observer. This article covers the basic anatomy and biomechanics of the wrist,
      and reviews in detail scapholunate ligament injury. This article also reviews and
      discusses the current relevant topics and issues surrounding scapholunate
      ligament injury.

PMID- 25068353
TI  - Discussion: Applications of acellular dermal matrix in revision breast
      reconstruction surgery.

PMID- 25068354
TI  - Beyond biologics: absorbable mesh as a low-cost, low-complication sling for
      implant-based breast reconstruction.

PMID- 25068355
TI  - Understanding the fascial supporting network of the breast: key ligamentous
      structures in breast augmentation and a proposed system of nomenclature.

PMID- 25068356
TI  - Reply: understanding the fascial supporting network of the breast: key
      ligamentous structures in breast augmentation and a proposed system of
      nomenclature.

PMID- 25068357
TI  - Management of congenital radial longitudinal deficiency: controversies and
      current concepts--an important correciton of the donor site.

PMID- 25068358
TI  - Reply: management of congenital radial longitudinal deficiency: controversies and
      current concepts-an important correciton of the donor site.

PMID- 25068359
TI  - Chimeric lateral supramalleolar artery perforator fibula free flap in the
      reconstruction of composite head and neck defects.

PMID- 25068360
TI  - Use of polyglycolic acid nerve conduit (neurotube) to alleviate pedicle kinking
      in microvascular anastomosis.

PMID- 25068361
TI  - Reply: use of polyglycolic Acid nerve conduit (neurotube) to alleviate pedicle
      kinking in microvascular anastomosis.

PMID- 25068362
TI  - Nanofat grafting: basic research and clinical applications.

PMID- 25068363
TI  - The best marketing strategy in aesthetic plastic surgery: evaluating patients'
      preferences by conjoint analysis.

PMID- 25068364
TI  - Reply: the best marketing strategy in aesthetic plastic surgery: evaluating
      patients' preferences by conjoint analysis.

PMID- 25068365
TI  - Columella rotation flap techniques for correction of columellar deviations.

PMID- 25068366
TI  - Ubersense: using a free video analysis app to evaluate and improve microsurgical
      skills.

PMID- 25068367
TI  - The "adorability" of the ipsilateral oblique view in unicoronal craniosynostosis:
      a silver lining for families.

PMID- 25068368
TI  - The manta ray flap: a technique for total glossectomy reconstruction.

PMID- 25068369
TI  - Revisiting nonvascularized partial muscle grafts: a novel use for prosthetic
      control.

PMID- 25068370
TI  - Conjoint deep inferior epigastric artery perforator flaps: case series of two
      patients with subfascial communication of the deep inferior epigastric vein.

PMID- 25068371
TI  - Novel technique for underlay mesh placement for ventral hernia repair.

PMID- 25068372
TI  - Heterologous antigen selection of camelid heavy chain single domain antibodies
      against tetrabromobisphenol A.
AB  - Tetrabromobisphenol A (TBBPA) is a ubiquitous flame retardant. A high-throughput
      immunoassay would allow for monitoring of human and environmental exposures as a
      part of risk assessment. Naturally occurring antibodies in camelids that are
      devoid of light chain, show great promise as an efficient tool in monitoring
      environmental contaminants, but they have been rarely used for small molecules.
      An alpaca was immunized with a TBBPA hapten coupled to thyroglobulin and a
      variable domain of heavy chain antibody (VHH) T3-15 highly selective for TBBPA
      was isolated from a phage displayed VHH library using heterologous coating
      antigens. Compared to the VHHs isolated using homologous antigens, VHH T3-15 had
      about a 10-fold improvement in sensitivity in an immunoassay. This assay, under
      the optimized conditions of 10% methanol in the assay buffer (pH 7.4), had an
      IC50 for TBBPA of 0.40 ng mL(-1) and negligible cross reactivity (<0.1%) with
      other tested analogues. After heating the VHH at 90  degrees C for 90 min about
      20% of the affinity for coating antigen T3-BSA remained. The recoveries of TBBPA
      from spiked soil and fetal bovine serum samples ranged from 90.3% to 110.7% by
      ELISA and agreed well with a liquid chromatography-tandem mass spectrometry
      method. We conclude the many advantages of VHH make them attractive for the
      development of immunoassays to small molecules. 

PMID- 25068374
TI  - Chemical vapor deposition of graphene on a "peeled-off" epitaxial Cu(111) foil: a
      simple approach to improved properties.
AB  - We present a simple approach to improving the quality of CVD grown graphene,
      exploiting a Cu(111) foil catalyst. The catalyst is epitaxially grown by
      evaporation on a single crystal sapphire substrate, thickened by electroplating,
      and peeled off. The exposed surface is atomically flat, easily reduced, and
      exclusively of (111) orientation. Graphene grown on this catalyst under
      atmospheric CVD conditions and without wet chemical prereduction produces single
      crystal domain sizes of several hundred micrometers in samples that are many
      centimeters in size. The graphene produced in this way can easily be transferred
      to other substrates using well-established techniques. We report mobilities
      extracted using field-effect (as high as 29 000 cm(2) V(-1) s(-1)) and Hall bar
      measurement (up to 10 100 cm(2) V(-1) s(-1)). 

PMID- 25068373
TI  - Adding maximum standard uptake value of primary lesion and lymph nodes in 18F
      fluorodeoxyglucose PET helps predict distant metastasis in patients with
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: To find out the most valuable parameter of 18F-Fluorodeoxyglucose
      positron emission tomography for predicting distant metastasis in nasopharyngeal
      carcinoma. METHODS: From June 2007 through December 2010, 43 non-metastatic NPC
      patients who underwent 18F-Fluorodeoxyglucose positron emission
      tomography/computed tomography (PET/CT) before radical Intensity-Modulated
      Radiation Therapy were enrolled and reviewed retrospectively. PET parameters
      including maximum standardized uptake value (SUV max), mean standardized uptake
      value (SUV mean), metabolic tumor volume (MTV), and total lesion glucose (TLG) of
      both primary tumor and cervical lymph nodes were calculated. Total SUV max were
      recorded as the sum of SUV max of primary tumor and cervical lymph nodes. Total
      SUV mean, Total MTV and Total TLG were calculated in the same way as Total SUV
      max. RESULTS: The median follow-up was 32 months (range, 23-68 months). Distant
      metastasis was the main pattern of treatment failure. Univariate analysis showed
      higher SUV max, SUV mean, MTV, and TLG of primary tumor, Total SUV max, Total
      MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer
      distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p =
      0.024, p = 0.033, p = 0.016, p = 0.015). In multivariate analysis, Total SUV max
      was the independent predictive factor for distant metastasis (p = 0.046).
      Spearman Rank correlation analysis showed mediate to strong correlationship
      between Total SUV max and SUV max-T, and between Total SUV max and SUV max
      N(Spearman coefficient: 0.568 and 0.834; p = 0.000 and p = 0.000). CONCLUSIONS:
      Preliminary results indicated that Total SUV max was an independently predictive
      factor for distant metastasis in patients of nasopharyngeal carcinoma treated
      with Intensity-Modulated Radiation Therapy.

PMID- 25068375
TI  - Treatment patterns among older patients with type 2 diabetes in the United
      States: a retrospective cohort study.
AB  - BACKGROUND: The American Diabetes Association consensus statement on the
      treatment of type 2 diabetes mellitus (T2DM) in older patients highlights the
      need for treatment pattern and effectiveness data from real-world settings and
      populations. This retrospective cohort study assessed the relative frequency of
      use of four commonly prescribed antihyperglycemia treatments for T2DM and
      quantified their effectiveness up to 2 years post-initiation. SUBJECTS AND
      METHODS: Within a large, U.S.-based, electronic health record database, we
      investigated usage of insulin, sulfonylureas, glucagon-like peptide-1(GLP-1)
      receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with
      T2DM, focusing on those >=65 years old, although younger patients were included
      for comparative purposes. RESULTS: Inclusion criteria were met by 77,440
      patients. Mean baseline glycosylated hemoglobin (HbA1c) levels for patients >=65
      years old varied among treatments: insulin (7.7% [61 mmol/mol]; n=3,311),
      sulfonylureas (7.0% [53 mmol/mol]; n=5,706), GLP-1 receptor agonists (7.1% [54
      mmol/mol]; n=260), and DPP-4 inhibitors (7.1% [54 mmol/mol]; n=1,096). Older
      patients demonstrated good glycemic control at therapy initiation and were
      prescribed glucose-lowering agents at lower HbA1c values compared with younger
      patients. A large proportion of older patients were prescribed sulfonylureas
      (56%) and insulin (34%) compared with GLP-1 receptor agonists (3.4%) and DPP-4
      inhibitors (12%), despite the associated risk of hypoglycemia. CONCLUSIONS:
      Patients initiating insulin and sulfonylureas demonstrated more sustained
      glycemic control compared with GLP-1 receptor agonists and DPP-4 inhibitors. A
      majority of older patients with T2DM was initiated on sulfonylureas and insulin
      at relatively low levels of HbA1c, a practice not entirely consistent with the
      recommendations of published guidelines.

PMID- 25068376
TI  - Blinking triggered by the change in the solvent accessibility of a fluorescent
      molecule.
AB  - The more a fluorescent molecule is exposed to a solvent, the faster its triplet
      excited state is quenched by molecular oxygen. The changes in the solvent
      accessibility of a fluorescent molecule were probed by measuring the duration of
      the off time during the blinking of the fluorescence, which enabled analysis of
      the function of a molecular beacon-type probe. 

PMID- 25068377
TI  - Mild hypervalent iodine mediated oxidative nitration of N-aryl sulfonamides.
AB  - An oxidative and acid-free method for the nitration of N-aryl sulfonamides has
      been developed using a combination of sodium nitrite as cheap and easy to handle
      NO2-source and the hypervalent iodine reagent PIFA as stoichiometric oxidant.
      Under very mild reaction conditions, the desired mononitrated aryl sulfonamides
      were isolated in up to 87% yield. This is the first example of an iodane-mediated
      oxidative nitration. 

PMID- 25068378
TI  - Single nucleotide polymorphism of RANKL and OPG genes may play a role in bone and
      joint injury in rheumatoid arthritis.
AB  - OBJECTIVES: This paper aims to investigate the influence of single-nucleotide
      polymorphisms (SNPs) in the receptor of activator of nuclear factor kappaB ligand
      (RANKL) gene (TNFSF11) and osteoprotegerin (OPG) gene (TNFRSF11B) on bone and
      joint injury in patients with rheumatoid arthritis (RA). METHODS: Two hundred RA
      patients and 201 matched controls were analysed by case-control design, and their
      samples were genotyped. Bone mineral density (BMD) and serum OPG and RANKL levels
      were measured. Clinical and laboratory parameters were recorded, and the
      radiographic changes in both hands of RA were evaluated by Sharp's method.
      RESULTS: Our results showed no significant differences in the distribution
      frequency of the alleles and genotypes of TNFRSF11B (rs2073618 and rs3102735) and
      TNFSF11 (rs2277438) between the RA group and controls (p>0.05). Compared to
      patients with TNFSF11 (rs2277438) AA or GG genotype, RA with TNFSF11 (rs2277438)
      AG genotype had significantly decreased BMD values at lumbar spine 3, lumbar
      spine 4, lumbar spine 2-4 (p<0.05-0.01), and apparently elevated Sharp scores
      (p<0.05), respectively. The RA group showed significantly higher serum levels of
      RANKL, RANKL/OPG ratio and a lower serum level of OPG than that of the controls
      (p<0.05-0.0001). RA patients with RANKL-rs2277438 heterozygotic genotype (AG) had
      significantly increased serum levels of RANKL (p<0.05), compared to homozygotic
      genotype (AA or GG). CONCLUSIONS: These results indicate that SNP of TNFRSF11B
      (rs2073618 and rs3102735) and TNFSF11 (rs2277438) may not be susceptibility
      factors for RA in Chinese Han population. SNP of TNFSF11 (rs2277438) may have an
      important influence on bone and joint injury in RA.

PMID- 25068379
TI  - Arterial age as a substitute for chronological age in the AGLA risk function
      could improve coronary risk prediction.
AB  - PRINCIPLES: As a result of the relatively low sensitivity of coronary risk
      charts, such as the Swiss coronary risk calculator (Arbeitsgruppe Lipide und
      Atherosklerose, AGLA), for detecting subjects with future myocardial infarction,
      the performance of arterial age (aa) as a surrogate marker for chronological age
      (ca) was tested. METHODS: In a practice based sample, burden of carotid plaque
      was obtained with ultrasound, using total plaque area (TPA). In this derivation
      cohort, sex-specific 5-year groups of mean TPA were calculated in subjects aged
      between 35 and 79 years. The arterial age formula was found by fitting an
      exponential function on these data. AGLAca and AGLAaa were tested externally for
      their ability to detect 13 myocardial infarctions in 684 subjects (validation
      cohort). RESULTS: The derivation cohort included 1,500 subjects (mean age 59 +/-
      9 years, mean TPA 54 +/- 52 mm2, 5% diabetics, 43% women). Arterial age was found
      to be y = 5.4175e0.0426x in men and y = 4.1942e0.0392x in women. Mean 10-year
      AGLAca coronary risk was comparable to AGLAaa (8% +/- 9% vs 9% +/- 15%). Receiver
      operating characteristic (ROC) analysis of AGLAca and AGLAaa results showed areas
      under the curve of 0.65 (p = 0.041) and 0.78 (p <0.0001), respectively, (p =
      0.041 for the difference = 0.13). This finding was also confirmed by a Cox
      proportional hazards regression model on patients' event-free survival (p = not
      significant for AGLAca, p = 0.0003 for AGLAaa). CONCLUSIONS: Arterial age derived
      from TPA could be used instead of chronological age in the AGLA coronary risk
      function. Further studies on the external validity and cost effectiveness of the
      additional ultrasound imaging study are necessary.

PMID- 25068380
TI  - Cycling around a curve: the effect of cycling speed on steering and gaze
      behavior.
AB  - Although it is generally accepted that visual information guides steering, it is
      still unclear whether a curvature matching strategy or a 'look where you are
      going' strategy is used while steering through a curved road. The current
      experiment investigated to what extent the existing models for curve driving also
      apply to cycling around a curve, and tested the influence of cycling speed on
      steering and gaze behavior. Twenty-five participants were asked to cycle through
      a semicircular lane three consecutive times at three different speeds while
      staying in the center of the lane. The observed steering behavior suggests that
      an anticipatory steering strategy was used at curve entrance and a compensatory
      strategy was used to steer through the actual bend of the curve. A shift of gaze
      from the center to the inside edge of the lane indicates that at low cycling
      speed, the 'look where you are going' strategy was preferred, while at higher
      cycling speeds participants seemed to prefer the curvature matching strategy.
      Authors suggest that visual information from both steering strategies contributes
      to the steering system and can be used in a flexible way. Based on a
      familiarization effect, it can be assumed that steering is not only guided by
      vision but that a short-term learning component should also be taken into
      account. 

PMID- 25068381
TI  - Novel steric stabilizers for lyotropic liquid crystalline nanoparticles:
      PEGylated-phytanyl copolymers.
AB  - Lyotropic liquid crystalline nanostructured particles (e.g., cubosomes and
      hexosomes) are being investigated as delivery systems for therapeutics in
      biomedical and pharmaceutical applications. Long term stability of these
      particulate dispersions is generally provided by steric stabilizers, typically
      commercially available amphiphilic copolymers such as Pluronic F127. Few examples
      exist of tailored molecular materials designed for lyotropic liquid crystalline
      nanostructured particle stabilization. A library of PEGylated-phytanyl copolymers
      (PEG-PHYT) with varying PEG molecular weights (200-14K Da) was synthesized to
      assess their performance as steric stabilizers for cubosomes and to establish
      structure-property relationships. The PEGylated-lipid copolymers were first found
      to self-assemble in excess water in the absence of cubosomes and also displayed
      thermotropic liquid crystal phase behavior under cross-polarized light
      microscopy. An accelerated stability assay was used to assess the performance of
      the copolymers, compared to Pluronic F127, for stabilizing phytantriol-based
      cubosomes. Several of the PEGylated-lipid copolymers showed steric stabilizer
      effectiveness comparable to Pluronic F127. Using synchrotron small-angle X-ray
      scattering and cryo-transmission electron microscopy, the copolymers were shown
      to retain the native internal lyotropic liquid crystalline structure, double
      diamond cubic phase (Q2(D)), of phytantriol dispersions; an important attribute
      for controlling downstream performance. 

PMID- 25068382
TI  - Role of gold(I) alpha-oxo carbenes in the oxidation reactions of alkynes
      catalyzed by gold(I) complexes.
AB  - The gas phase structures of gold(I) complexes formed by intermolecular oxidation
      of selected terminal (phenylacetylene) and internal alkynes (2-butyne, 1
      phenylpropyne, diphenylacetylene) were investigated using tandem mass
      spectrometry and ion spectroscopy in conjunction with quantum-chemical
      calculations. The experiments demonstrated that the primarily formed beta-gold(I)
      vinyloxypyridinium complexes readily undergo rearrangement, dependent on their
      substituents, to either gold(I) alpha-oxo carbenenoids (a synthetic surrogate of
      the alpha-oxo carbenes) or pyridine adducts of gold(I) enone complexes in the
      condensed phase and that the existence of naked alpha-oxo carbenes is highly
      improbable. Isotopic labeling experiments performed with the reaction mixtures
      clearly linked the species that exist in solution to the ions transferred to the
      gas phase. The ions were then fully characterized by CID experiments and IRMPD
      spectroscopy. The conclusions based on the experimental observations perfectly
      correspond with the results from quantum-chemical calculations. 

PMID- 25068383
TI  - Formation of a [2]pseudorotaxane based on a pillar[5]arene and a rigid guest in
      solution and in the solid state.
AB  - A pillar[5]arene with mono(ethylene oxide) substituents could form a highly
      stable [2]pseudorotaxane with a rigid guest both in solution and in the solid
      state. 

PMID- 25068384
TI  - Formation of interfacial layer and long-term cyclability of Li-O2 batteries.
AB  - The long-term operation of Li-O2 batteries under full discharge/charge conditions
      is investigated in a glyme-based electrolyte. The formation of stable interfacial
      layer on the electrode surface during the initial cycling stabilizes reaction
      products at subsequent cycling stages as demonstrated by quantitative analyses of
      the discharge products and the gases released during charging. There is a quick
      switch from the predominant formation of Li2O2 to the predominant formation of
      side products during the first few cycles. However, after the formation of the
      stable interfacial layer, the yield of Li2O2 in the reaction products is
      stabilized at about 33-40%. Extended cycling under full discharge/charge
      conditions is achievable upon selection of appropriate electrode materials
      (carbon source and catalyst) and cycling protocol. Further investigation on the
      interfacial layer, which in situ forms on air electrode, may increase the long
      term yield of Li2O2 during the cycling and enable highly reversible Li-O2
      batteries required for practical applications. 

PMID- 25068386
TI  - Markov logic networks for optical chemical structure recognition.
AB  - Optical chemical structure recognition is the problem of converting a bitmap
      image containing a chemical structure formula into a standard structured
      representation of the molecule. We introduce a novel approach to this problem
      based on the pipelined integration of pattern recognition techniques with
      probabilistic knowledge representation and reasoning. Basic entities and
      relations (such as textual elements, points, lines, etc.) are first extracted by
      a low-level processing module. A probabilistic reasoning engine based on Markov
      logic, embodying chemical and graphical knowledge, is subsequently used to refine
      these pieces of information. An annotated connection table of atoms and bonds is
      finally assembled and converted into a standard chemical exchange format. We
      report a successful evaluation on two large image data sets, showing that the
      method compares favorably with the current state-of-the-art, especially on
      degraded low-resolution images. The system is available as a web server at
      http://mlocsr.dinfo.unifi.it.

PMID- 25068385
TI  - Mono- and binuclear copper(I) complexes of thionucleotide analogues and their
      catalytic activity on the synthesis of dihydrofurans.
AB  - The reaction of copper(I) halides with 2-thiouracil (TUC), 6-methyl-2-thiouacil
      (MTUC), and 4-methyl-2-mercaptopyrimidine (MPMTH) in the presence of
      triphenylphosphine (tpp) in a 1:1:2 molar ratio results in a mixed-ligand
      copper(I) complex with the formulas [Cu2(tpp)4(TUC)Cl] (1), [Cu2(tpp)4(MTUC)Cl]
      (2), [Cu(tpp)2(MPMTH)Cl].(1)/2CH3OH (3), [Cu(tpp)2(MTUC)Br] (4), and
      [Cu(tpp)2(MTUC)I].(1)/2CH3CN (5). The complexes have been characterized by FT-IR,
      (1)H NMR, and UV-vis spectroscopic techniques and single-crystal X-ray
      crystallography. Complexes 1 and 2 are binuclear copper(I) complexes. Two
      phosphorus atoms from tpp ligands are coordinated to the copper(I) ions, forming
      two units that are linked to each other by a deprotonated TUC or MTUC chelating
      ligand through a sulfur bridge. A linear Cu-S-Cu moiety is formed. The
      tetrahedral geometry around the metal centers is completed by the nitrogen-donor
      atom from the TUC or MTUC ligand for the one unit, while for the other one, it is
      completed by the chloride anion. Two phosphorus atoms from two tpp ligands, one
      sulfur atom from MPMTH or MTUC ligand, and one halide anion (Cl, Br, and I) form
      a tetrahedron around the copper ion in 3-5 and two polymorphic forms of 4 (4a and
      4b). In all of the complexes, either mono- or binuclear intramolecular O-H...X
      hydrogen bonds enhance the stability of the structures. On the other hand, in
      almost all cases of mononuclear complexes (with the exception of a symmetry
      independent molecule in 4a), intermolecular NH...O hydrogen-bonding interactions
      lead to dimerization. Complexes 1-5 were studied for their catalytic activity for
      the intermolecular cycloaddition of iodonium ylides toward dihydrofuran formation
      by HPLC, (1)H NMR, and LC-HRMS spectroscopic techniques. The results show that
      the geometry and halogen and ligand types have a strong effect on the catalytic
      properties of the complexes. The highest yield of dihydrofurans was obtained when
      "linear" complexes 1 and 2 were used as the catalysts. The activity of the metal
      complexes on the copper(I)-catalyzed and uncatalyzed intramolecular cycloaddition
      of iodonium ylide is rationalized through electronic structure calculation
      methods, and the results are compared with the experimental ones. 

PMID- 25068387
TI  - Ultrashort cationic naphthalene-derived self-assembled peptides as antimicrobial
      nanomaterials.
AB  - Self-assembling dipeptides conjugated to naphthalene show considerable promise as
      nanomaterial structures, biomaterials, and drug delivery devices. Biomaterial
      infections are responsible for high rates of patient mortality and morbidity. The
      presence of biofilm bacteria, which thrive on implant surfaces, are a huge burden
      on healthcare budgets, as they are highly resistant to current therapeutic
      strategies. Ultrashort cationic self-assembled peptides represent a highly
      innovative and cost-effective strategy to form antibacterial nanomaterials.
      Lysine conjugated variants display the greatest potency with 2% w/v NapFFKK
      hydrogels significantly reducing the viable Staphylococcus epidermidis biofilm by
      94%. Reducing the size of the R-group methylene chain on cationic moieties
      resulted in reduction of antibiofilm activity. The primary amine of the
      protruding R-group tail may not be as readily available to interact with
      negatively charged bacterial membranes. Cryo-SEM, FTIR, CD spectroscopy, and
      oscillatory rheology provided evidence of supramolecular hydrogel formation at
      physiological pH (pH 7.4). Cytotoxicity assays against murine fibroblast (NCTC
      929) cell lines confirmed the gels possessed reduced cytotoxicity relative to
      bacterial cells, with limited hemolysis upon exposure to equine erythrocytes. The
      results presented in this paper highlight the significant potential of ultrashort
      cationic naphthalene peptides as future biomaterials. 

PMID- 25068388
TI  - Cirrhosis, liver transplantation and HIV infection are risk factors associated
      with hepatitis E virus infection.
AB  - BACKGROUND: Acute and chronic hepatitis E have been associated with high
      mortality and development of cirrhosis, particularly in solid-organ recipients
      and patients infected by human immunodeficiency virus. However, data regarding
      the epidemiology of hepatitis E in special populations is still limited. AIMS:
      Investigate seroprevalence and possible factors associated with HEV infection in
      a large cohort of immunosuppressed patients. METHODS: Cross-sectional study
      testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332
      liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non
      transplanted patients with chronic liver disease, 238 HIV-infected patients and
      200 healthy controls. RESULTS: IgG anti-HEV was detected in 3.5% controls, 3.7%
      kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who
      developed post-transplant cirrhosis (p<0.01). In patients with chronic liver
      disease, IgG anti-HEV was also statistically higher in those with liver cirrhosis
      (2% vs 17.5%, p<0.01). HIV-infected patients showed an IgG anti-HEV rate of 9.2%,
      higher than those patients without HIV infection (p<0.03). Multivariate analysis
      showed that the factors independently associated with anti-HEV detection were
      liver cirrhosis, liver transplantation and HIV infection (OR: 7.6, 3.1 and 2.4).
      HCV infection was a protective factor for HEV infection (OR: 0.4). CONCLUSIONS:
      HEV seroprevalence was high in liver transplant recipients, particularly those
      with liver cirrhosis. The difference in anti-HEV prevalence between Liver and
      Kidney transplanted cases suggests an association with advanced liver disease.
      Further research is needed to ascertain whether cirrhosis is a predisposing
      factor for HEV infection or whether HEV infection may play a role in the
      pathogeneses of cirrhosis.

PMID- 25068389
TI  - Gleaning knowledge from data in the intensive care unit.
AB  - It is often difficult to accurately predict when, why, and which patients develop
      shock, because signs of shock often occur late, once organ injury is already
      present. Three levels of aggregation of information can be used to aid the
      bedside clinician in this task: analysis of derived parameters of existing
      measured physiologic variables using simple bedside calculations (functional
      hemodynamic monitoring); prior physiologic data of similar subjects during
      periods of stability and disease to define quantitative metrics of level of
      severity; and libraries of responses across large and comprehensive collections
      of records of diverse subjects whose diagnosis, therapies, and course is already
      known to predict not only disease severity, but also the subsequent behavior of
      the subject if left untreated or treated with one of the many therapeutic
      options. The problem is in defining the minimal monitoring data set needed to
      initially identify those patients across all possible processes, and then
      specifically monitor their responses to targeted therapies known to improve
      outcome. To address these issues, multivariable models using machine learning
      data-driven classification techniques can be used to parsimoniously predict
      cardiorespiratory insufficiency. We briefly describe how these machine learning
      approaches are presently applied to address earlier identification of
      cardiorespiratory insufficiency and direct focused, patient-specific management. 

PMID- 25068390
TI  - Selenoprotein P is the major selenium transport protein in mouse milk.
AB  - Selenium is transferred from the mouse dam to its neonate via milk. Milk contains
      selenium in selenoprotein form as selenoprotein P (Sepp1) and glutathione
      peroxidase-3 (Gpx3) as well as in non-specific protein form as selenomethionine.
      Selenium is also present in milk in uncharacterized small-molecule form. We
      eliminated selenomethionine from the mice in these experiments by feeding a diet
      that contained sodium selenite as the source of selenium. Selenium-replete dams
      with deletion of Sepp1 or Gpx3 were studied to assess the effects of these genes
      on selenium transfer to the neonate. Sepp1 knockout caused a drop in milk
      selenium to 27% of the value in wild-type milk and a drop in selenium acquisition
      by the neonates to 35%. In addition to decreasing milk selenium by eliminating
      Sepp1, deletion of Sepp1 causes a decline in whole-body selenium, which likely
      also contributes to the decreased transfer of selenium to the neonate. Deletion
      of Gpx3 did not decrease milk selenium content or neonate selenium acquisition by
      measurable amounts. Thus, when the dam is fed selenium-adequate diet (0.25 mg
      selenium/kg diet), milk Sepp1 transfers a large amount of selenium to neonates
      but the transfer of selenium by Gpx3 is below detection by our methods. 

PMID- 25068391
TI  - Palliative care for severely affected patients with multiple sclerosis: when and
      why? Results of a Delphi survey of health care professionals.
AB  - BACKGROUND: Patients severely affected by multiple sclerosis (MS) present with
      complex symptoms and needs requiring an interdisciplinary care approach.
      OBJECTIVE: Analysis of when and why specialized palliative care integration would
      be beneficial via examining health care professionals' attitudes. DESIGN: A two
      round online Delphi study and expert workshop were undertaken and analyzed
      descriptively. SETTING/SUBJECTS: Following an extensive online search, 164
      professionals with expertise in treating and caring for severely affected
      patients with MS were contacted. Professionals included neurologists, urologists,
      general practitioners, MS nurses, speech therapists, physiotherapists,
      psychologists, and palliative care physicians. Forty-six consented to
      participate: 33 of 46 (71.4%) and 15 of 33 (45.5%) experts responded in the first
      and second round, respectively. RESULTS: Consensus was reached among all
      respondents (100%) defining the term "severely affected": 78.8% and 86.7%,
      respectively, thought that specialized palliative care should begin once the
      disease has progressed (Expanded Disability Status Scale [EDSS]>6 and nursing
      care required). When the need exists for communication about disease progression
      (93.3%), psychological support (93.3%), relatives support (93.3%), and pain
      medication (86.7%) specialized palliative care should be consulted. Specialized
      palliative homecare was rated (93.3%) "very important." The workshop documented
      the paucity of home visits and specialized MS care in nursing homes. CONCLUSIONS:
      Our results clearly identified specific areas in which palliative care will
      likely prove to be a valuable asset in the treatment course of MS. This
      information should serve clinicians, indicating when to consider palliative care
      services and help further reduce or eliminate uncertainty about how palliative
      care can be integrated in the course of MS.

PMID- 25068392
TI  - Exploring the interaction of a micelle entrapped biologically important proton
      transfer probe with the model transport protein bovine serum albumin.
AB  - This article describes the interaction of a micelle entrapped pharmaceutically
      important isoindole fused imidazole derivative, namely, 1-(2-hydroxy-5-methyl
      phenyl)-3,5-dioxo-1H-imidazo-[3,4-b] isoindole (ADII), with the model transport
      protein bovine serum albumin (BSA). Different spectroscopic techniques such as
      steady state absorption, emission, circular dichroism, dynamic light scattering,
      etc., have been employed to explore preferential interaction of this drug
      template with micelles and protein BSA. Binding of ADII with BSA is found to be
      enormously modified when it is released from the micellar environment. The
      binding constant of the ADII-BSA complex is reduced when the probe is released
      from anionic SDS micelle, whereas the binding is observed to be strengthened in
      cationic CTAB micellar medium due to the formation of a 1:2 complex (ADII-BSA).
      Time-resolved studies also support our steady state findings that the released
      drug from the micellar environment is found to be strongly bound with the protein
      BSA. Circular dichroism (CD) and dynamic light scattering (DLS) study reveals
      that the secondary structure of BSA gets some stabilization in SDS medium after
      binding of drug template to protein. The probable binding location of the probe
      within the protein cavity (hydrophilic subdomain IA) has been explored from an
      AutoDock-based blind docking simulation study. 

PMID- 25068393
TI  - Prevalence of physical activity and sedentary behavior among adults with
      cardiovascular disease in the United States.
AB  - BACKGROUND: Physical activity (PA) is recommended for primary and secondary
      prevention of cardiovascular disease (CVD). This study described the prevalence
      of self-reported and accelerometer-measured PA and sedentary behavior, using a
      nationally representative sample from the United States, a subset of whom had
      CVD, including angina, coronary heart disease (CHD), congestive heart failure
      (CHF), and myocardial infarction (MI). METHODS: Using the most recently available
      accelerometer data (combined 2003-2006) from the National Health and Nutrition
      Examination Survey, the study sample included 680 adults with CVD, who completed
      a questionnaire and wore an ActiGraph accelerometer for 1 week. A group without
      CVD (n = 1000) was also selected as the referent, with similar age, gender, and
      race/ethnic distributions as those with CVD (angina, CHD, CHF, MI) to compare PA
      and sedentary behavior estimates. Percentages and means were weighted to reflect
      the US population from 2003 to 2006. RESULTS: Among those with CVD, the
      proportion of individuals who engaged in self-reported past-month, moderate
      intensity leisure activity ranged from 39.7% (CHF) to 53.8% (CHD) and vigorous
      intensity leisure activity from 12.9% (CHF) to 18.4% (CHD), with walking being
      the most commonly reported activity. Television watching >=4 h/d ranged from
      36.2% (MI) to 44.8% (CHF). Using accelerometry, moderate- to vigorous-intensity
      PA ranged from 8.6 (CHF) to 11.4 min/d (angina). Sedentary behavior ranged from
      9.6 (angina) to 10.1 h/d (CHF). All 4 CVD groups had lower leisure activity and
      moderate- to vigorous-intensity PA, and higher television watching and sedentary
      behavior, when compared with the referent group. CONCLUSIONS: Further efforts are
      needed to encourage PA and reduce sedentary behavior for secondary prevention of
      CVD.

PMID- 25068394
TI  - Evaluation of the quality of clinical guidelines for cardiac rehabilitation: a
      critical review.
AB  - PURPOSE: To evaluate the quality of clinical guidelines (CGs) for cardiac
      rehabilitation and to critically appraise exercise-related recommendations.
      METHODS:  DESIGN: critical review. DATA SOURCES: main search engines, databases,
      clearinghouses, and guideline developers. STUDY SELECTION: We included evidence
      based CGs specific to cardiac rehabilitation with recommendations for the period
      after diagnosis of myocardial infarction or acute coronary syndrome. Clinical
      guidelines needed to include an exercise component and at least 1 additional
      component in the cardiac rehabilitation program. Data extraction and appraisal:
      We evaluated the quality of GCs, using the Appraisal of Guidelines for Research
      and Evaluation Instrument, second version. Three reviewers independently
      extracted data, appraised the quality of included CGs, and resolved disagreements
      by consensus. RESULTS: Nine guidelines were included. The average scores were
      79.84%, 59.88%, 55.56%, 85.18%, 48.92%, and 56.79% for the domains of scope and
      purpose, stakeholder involvement, rigor of development, clarity and presentation,
      applicability, and editorial independence, respectively. The majority of
      guidelines recommended low- to moderate-intensity aerobic and resistance
      exercises, with moderate variability in the frequency and duration of sessions.
      CONCLUSIONS: Clinical guidelines consistently recommended aerobic and resistance
      exercises. Overall, our critical review showed that the quality of CGs was at
      least moderate, with the greatest deficiencies being related to applicability and
      rigor of development domains.

PMID- 25068395
TI  - Characterization of the prostate-specific antigen (PSA) catalytic mechanism: a
      pre-steady-state and steady-state study.
AB  - Prostate-specific antigen (PSA), an enzyme of 30 kDa grouped in the kallikrein
      family is synthesized to high levels by normal and malignant prostate epithelial
      cells. Therefore, it is the main biomarker currently used for early diagnosis of
      prostate cancer. Here, presteady-state and steady-state kinetics of the PSA
      catalyzed hydrolysis of the fluorogenic substrate Mu-His-Ser-Ser-Lys-Leu-Gln-AMC
      (spanning from pH 6.5 to pH 9.0, at 37.0 degrees C) are reported. Steady-state
      kinetics display at every pH value a peculiar feature, represented by an initial
      "burst" phase of the fluorescence signal before steady-state conditions are
      taking place. This behavior, which has been already observed in other members of
      the kallikrein family, suggests the occurrence of a proteolytic mechanism
      wherefore the acylation step is faster than the deacylation process. This feature
      allows to detect the acyl intermediate, where the newly formed C-terminal
      carboxylic acid of the cleaved substrate forms an ester bond with the -OH group
      of the Ser195 catalytic residue, whereas the AMC product has been already
      released. Therefore, the pH-dependence of the two enzymatic steps (i.e.,
      acylation and deacylation) has been separately characterized, allowing the
      determination of pKa values. On this basis, possible residues are tentatively
      identified in PSA, which might regulate these two steps by interacting with the
      two portions of the substrate. 

PMID- 25068396
TI  - Determination of MIC distribution of arbekacin, cefminox, fosfomycin, biapenem
      and other antibiotics against gram-negative clinical isolates in South India: a
      prospective study.
AB  - OBJECTIVES: To determine the in vitro activity of antibiotics, including
      arbekacin, cefminox, fosfomycin and biapenem which are all still unavailable in
      India, against Gram-negative clinical isolates. METHODS: We prospectively
      collected and tested all consecutive isolates of Escherichia coli, Klebsiella
      spp., Pseudomonas aeruginosa and Acinetobacter spp. from blood, urine and sputum
      samples between March and November 2012. The minimum inhibition concentration
      (MIC) of 16 antibiotics was determined by the broth micro-dilution method.
      RESULTS: Overall 925 isolates were included; 211 E. coli, 207 Klebsiella spp.,
      153 P. aeruginosa, and 354 Acinetobacter spp. The MIC50 and MIC90 were high for
      cefminox, biapenem and arbekacin for all pathogens but interpretative criteria
      were not available. The MIC50 was categorized as susceptible for a couple of
      antibiotics, including piperacillin/tazobactam, carbapenems and amikacin, for E.
      coli, Klebsiella spp. and P. aeruginosa. However, for Acinetobacter spp., the
      MIC50 was categorized as susceptible only for colistin. On the other hand,
      fosfomycin was the only antibiotic that inhibited 90% of E. coli and Klebsiella
      spp. isolates, while 90% of P. aeruginosa isolates were inhibited only by
      colistin. Finally, 90% of Acinetobacter spp. isolates were not inhibited by any
      antibiotic tested. CONCLUSION: Fosfomycin and colistin might be promising
      antibiotics for the treatment of infections due to E. coli or Klebsiella spp. and
      P. aeruginosa, respectively, in India; however, clinical trials should first
      corroborate the in vitro findings. The activity of tigecycline should be
      evaluated, as this is commonly used as last-resort option for the treatment of
      multidrug-resistant Acinetobacter infections.

PMID- 25068397
TI  - Pathogenicity of three entomopathogenic fungi to Matsucoccus matsumurae.
AB  - Matsucoccus matsumurae (Kuwana) (Hemiptera: Coccoidea: Matsucoccidae) is an
      invasive alien species and a destructive pest of two native Chinese pines, Pinus
      tabulaeformis Carr. and P. massoniana Lamb., throughout the eastern regions of
      China. The pathogenicity of three entomopathogenic fungi, Lecanicillium lecanii
      strain V3.4504 and V3.4505, Fusarium incarnatum-equiseti strain HEB01 and
      Lecanicillium fungicola strain HEB02, against M. matsumurae was tested in four
      instars, to evaluate their potential as a biological control agent. The results
      showed that the four strains caused disease and death of the scale insect, among
      which the L. lecanii strains V3.4504 and V3.4505 displayed stronger virulence
      than the F. incarnatum-equiseti strains HEB01 and L. fungicola strain HEB02 to M.
      matsumurae in the 2nd-instar nymphs and the adult females. Furthermore, L.
      lecanii V3.4505 was most virulent to M. matsumurae. The adult females and the
      male 3rd-instar nymphs of M. matsumurae were susceptible to L. lecanii V3.4505;
      the adult females were more susceptible at LT50 = 1.96 than the 3rd-instar nymphs
      at LT50 = 5.67. The body surface structure, cuticle thickness and wax secretions
      of M. matsumurae impacted the fungal infection. L. lecanii is a promising
      biocontrol agent, and newly emerged male 3rd-instar nymphs and adult females are
      a crucial period of the insect's life cycle for M. matsumurae biocontrol. 

PMID- 25068398
TI  - A longitudinal study on children's music training experience and academic
      development.
AB  - This study examined the relation between long-term music training and child
      development based on 250 Chinese elementary school students' academic development
      of first language (L1), second language (L2), and mathematics. We found that
      musician children outperformed non-musician children only on musical achievement
      and second language development. Additionally, although music training appeared
      to be correlated with children's final academic development of L1, L2, and
      mathematics, it did not independently contribute to the development of L1 or
      mathematical skills. Our findings suggest caution in interpreting the positive
      findings on the non-musical cognitive benefits of music learning. 

PMID- 25068400
TI  - Effect of replacing dietary vitamin E by sage on performance and meatiness of
      spent hens, and the oxidative stability of sausages produced from their meat.
AB  - A total of 3960 hens (half ISA Warren and half Dekalb White) were housed in 18
      compartments with 220 hens each. The effect of replacing dietary vitamin E by
      sage on productivity, meat yield and oxidative stability of sausages was studied.
      One third of all animals received either a vitamin E deficient diet (negative
      control) or diets supplemented with 30 mg/kg alpha-tocopherylacetate (positive
      control) or 25 g sage leaves/kg. At slaughter, meat yield was assessed and
      sausages were produced (n = 12 per treatment). The omission of vitamin E did not
      impair the oxidative stability of the raw sausage material or the spiced sausages
      in comparison to the positive control. Sage supplementation improved oxidative
      stability after 7 m of frozen storage, but not after 1, 4 and 10 m. Spice
      addition during meat processing had an antioxidant effect regardless of dietary
      treatment. Diet supplementation of any type did not affect laying performance and
      sausage meat yield. Feeding antioxidants to spent hens seemed to be not as
      efficient as in growing chickens, while seasoning with spices during sausage
      production proved to be a feasible way to delay lipid oxidation.

PMID- 25068401
TI  - Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates
      multiple cellular anti-viral pathways and exhibits a severe decrease in
      virulence.
AB  - Although the production of single gene knockout viruses is a useful strategy to
      study viral gene functions, the redundancy of many host interactive genes within
      a complex viral genome can obscure their collective functions. In this study, a
      rabbit-specific poxvirus, myxoma virus (MYXV), was genetically altered to disrupt
      multiple members of the poxviral ankyrin-repeat (ANK-R) protein superfamily, M
      T5, M148, M149 and M150. A particularly robust activation of the NF-kappaB
      pathway was observed in A549 cells following infection with the complete ANK-R
      knockout (vMyx-ANKsKO). Also, an increased release of IL-6 was only observed upon
      infection with vMyx-ANKsKO. In virus-infected rabbit studies, vMyx-ANKsKO was the
      most extensively attenuated and produced the smallest primary lesion of all ANK-R
      mutant constructs. This study provides the first insights into the shared
      functions of the poxviral ANK-R protein superfamily in vitro and in vivo. 

PMID- 25068402
TI  - Viral fitness does not correlate with three genotype displacement events
      involving infectious hematopoietic necrosis virus.
AB  - Viral genotype displacement events are characterized by the replacement of a
      previously dominant virus genotype by a novel genotype of the same virus species
      in a given geographic region. We examine here the fitness of three pairs of
      infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major
      genotype displacement events in Washington state over the last 30 years to
      determine whether increased virus fitness correlates with displacement. Fitness
      was assessed using in vivo assays to measure viral replication in single
      infection, simultaneous co-infection, and sequential superinfection in the
      natural host, steelhead trout. In addition, virion stability of each genotype was
      measured in freshwater and seawater environments at various temperatures. By
      these methods, we found no correlation between increased viral fitness and
      displacement in the field. These results suggest that other pressures likely
      exist in the field with important consequences for IHNV evolution. 

PMID- 25068403
TI  - The role of miRNA-34a as a prognostic biomarker for cirrhotic patients with
      portal hypertension receiving TIPS.
AB  - BACKGROUND: Circulating miRNA-34a is increased in blood of patients with
      different liver diseases when compared to healthy controls. However, the origin
      of miRNA-34a and its possible relationship with hemodynamics and outcome in
      cirrhotic patients with portal hypertension is unknown. We analyzed the levels of
      miRNA-34a in cirrhotic patients with severe portal hypertension. METHODS: We
      included 60 cirrhotic patients receiving TIPS for prevention of rebleeding and/or
      therapy-refractory ascites. miRNA-34a levels were measured using qPCR and
      normalized by SV-40 in the portal and hepatic venous blood of these patients
      taken at TIPS procedure. Hemodynamic and clinical parameters were assessed before
      TIPS and during follow-up. RESULTS: Levels of miRNA-34a were higher in the
      hepatic vein than in the portal vein. Circulating miRNA-34a in the hepatic vein
      correlated with ALT, CHE and sodium excretion after TIPS. miRNA-34a showed no
      correlation with portal pressure, but its levels in the portal vein correlated
      inversely with the congestion index. Interestingly, the levels of miRNA-34a in
      the portal and hepatic vein showed inverse correlation with arterial pressure.
      Furthermore, levels of miRNA-34a in the hepatic vein had a predictive value for
      survival, but MELD, creatinine at short-time follow-up 14 days after TIPS
      insertion and portal pressure after TIPS performed better. CONCLUSION: This study
      demonstrates for the first time, that miRNA-34a may originate to a large extent
      from the liver. Even though higher levels of miRNA-34a are possibly associated
      with better survival at long-term follow-up in cirrhotic patients with severe
      portal hypertension receiving TIPS, classical prognostic parameters predict the
      survival better.

PMID- 25068404
TI  - Enhanced cellular preservation by clay minerals in 1 billion-year-old lakes.
AB  - Organic-walled microfossils provide the best insights into the composition and
      evolution of the biosphere through the first 80 percent of Earth history. The
      mechanism of microfossil preservation affects the quality of biological
      information retained and informs understanding of early Earth palaeo
      environments. We here show that 1 billion-year-old microfossils from the non
      marine Torridon Group are remarkably preserved by a combination of clay minerals
      and phosphate, with clay minerals providing the highest fidelity of preservation.
      Fe-rich clay mostly occurs in narrow zones in contact with cellular material and
      is interpreted as an early microbially-mediated phase enclosing and replacing the
      most labile biological material. K-rich clay occurs within and exterior to cell
      envelopes, forming where the supply of Fe had been exhausted. Clay minerals inter
      finger with calcium phosphate that co-precipitated with the clays in the sub-oxic
      zone of the lake sediments. This type of preservation was favoured in sulfate
      poor environments where Fe-silicate precipitation could outcompete Fe-sulfide
      formation. This work shows that clay minerals can provide an exceptionally high
      fidelity of microfossil preservation and extends the known geological range of
      this fossilization style by almost 500 Ma. It also suggests that the best
      preserved microfossils of this time may be found in low-sulfate environments.

PMID- 25068405
TI  - The validation of housekeeping genes as a reference in quantitative Real Time PCR
      analysis: application in the milk somatic cells and frozen whole blood of goats
      infected with caprine arthritis encephalitis virus.
AB  - The validation of housekeeping genes (HKGs) for normalization of RNA expression
      in Real-Time PCR is crucial to obtain the most reliable results. There is limited
      information on reference genes used in the study of gene expression in milk
      somatic cells and the frozen whole blood of goats. Thus, the aim of this study
      was to propose the most stable housekeeping genes that can be used as a reference
      in Real-Time PCR analysis of milk somatic cells and whole blood of goats infected
      with caprine arthritis encephalitis virus (CAEV). Animals were divided into two
      groups: non-infected (N=13) and infected with CAEV (N=13). Biological material
      (milk somatic cells and whole blood) was collected 4 times during the lactation
      period (7, 30, 100 and 240days post-partum). The expression levels of candidate
      reference genes were analyzed using geNorm and NormFinder software. The stability
      of candidates for reference gene expression was analyzed for CAEV-free (control)
      and CAEV-infected groups, and also for both groups together (combined group). The
      stability of expression of beta-actin (ACTB), glyceraldehyde-3P-dehydrogenase
      (GAPDH), cyclophilin A (PPIA), RNA18S1, ubiquilin (UBQLN1) and ribosomal protein
      large subunit P0 (RPLP0) was determined in milk somatic cells, while ACTB, PPIA,
      RPLP0, succinate dehydrogenase complex subunit A (SDHA), zeta polypeptide
      (YWHAZ), battenin (CLN3), eukaryotic translation initiation factor 3K (EIF3K) and
      TATA box-binding protein (TBP) were measured in frozen whole blood of goats. PPIA
      and RPLP0 were considered as the most suitable internal controls as they were
      stably expressed in milk somatic cells regardless of disease status, according to
      NormFinder software. Furthermore, geNorm results indicated the expression of
      PPIA/RPLP0 genes as the best combination under these experimental conditions. The
      results of frozen whole blood analysis using NormFinder software revealed that
      the most stable reference gene in control, CAEV-infected and combined groups is
      YWHAZ, and - according to the geNorm results - the combined expression of
      PPM/YWHAZ genes is the best reference in the presented experiment. The usefulness
      in gene expression analysis of whole blood samples frozen immediately in liquid
      nitrogen and stored at -80 degrees C was also proved.

PMID- 25068406
TI  - The evolutionary history of the genes involved in the biosynthesis of the
      antioxidant ergothioneine.
AB  - Ergothioneine (EGT) is a histidine betaine derivative that exhibits antioxidant
      action in humans. EGT is primarily synthesized by fungal species and a number of
      bacterial species. A five-gene cluster (egtA, egtB, egtC, egtD &egtE) responsible
      for EGT production in Mycobacteria smegmatis has recently been identified. The
      first fungal biosynthetic EGT gene (NcEgt-1) has also been identified in
      Neurospora crassa. NcEgt-1 contains domains similar to those found in M.
      smegmatis egtB and egtD. EGT is biomembrane impermeable. Here we inferred the
      evolutionary history of the EGT cluster in prokaryotes as well as examining the
      phyletic distribution of Egt-1 in the fungal kingdom. A genomic survey of 2509
      prokaryotes showed that the five-gene EGT cluster is only found in the
      Actinobacteria. Our survey identified more than 400 diverse prokaryotes that
      contain genetically linked orthologs of egtB and egtD. Phylogenetic analyses of
      Egt proteins show a complex evolutionary history and multiple incidences of
      horizontal gene transfer. Our analysis also identified two independent incidences
      of a fusion event of egtB and egtD in bacterial species. A genomic survey of over
      100 fungal genomes shows that Egt-1 is found in all fungal phyla, except species
      that belong to the Saccharomycotina subphylum. This analysis provides a
      comprehensive analysis of the distribution of the key genes involved in the
      synthesis of EGT in prokaryotes and fungi. Our phylogenetic inferences illuminate
      the complex evolutionary history of the genes involved in EGT synthesis in
      prokaryotes. The potential to synthesize EGT is a fungal trait except for species
      belonging to the Saccharomycotina subphylum.

PMID- 25068407
TI  - The possible implication of the S250C variant of the autoimmune regulator protein
      in a patient with autoimmunity and immunodeficiency: in silico analysis suggests
      a molecular pathogenic mechanism for the variant.
AB  - Autoimmunity can develop from an often undetermined interplay of genetic and
      environmental factors. Rare forms of autoimmune conditions may also result from
      single gene mutations as for autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy, an autosomal recessive disease associated with mutated forms of the
      autoimmune regulator gene. It was proposed that genetic variability in the
      autoimmune regulator locus, in particular heterozygous loss-of-function
      mutations, might favor the development of organ-specific autoimmunity by
      affecting the presentation of self-antigens in the thymus. Indeed, heterozygous
      mutations of the autoimmune regulator gene were reported in patients with organ
      specific autoimmunity. Also, in primary immunodeficiencies, a breakdown in
      central/peripheral tolerance frequently produces association with autoimmunity.
      The causative link may involve a common genetic background and several gene
      defects have been identified as putative culprits. We report a unique patient, a
      14 year old male from Lazio region, affected by common variable immunodeficiency
      associated with autoimmune manifestations (alopecia, onychodystrophy) and
      heterozygote for the S250C variant located in the SAND domain of the autoimmune
      regulator gene protein. To our knowledge this is the first report of the S250C
      variant in a patient bearing this unusual combination of autoimmunity and
      immunodeficiency. To obtain insights into the possible molecular effects of the
      S250C variant, we have carried out an in silico analysis of the SAND domain
      structure of the autoimmune regulator protein. In particular, homology modeling
      has allowed us to observe that the cysteine introduced by the S250C variant is
      surrounded by cationic residues, and by means of molecular dynamics simulations
      together with pKa calculations, we have shown that these residues remain stably
      proximal to cysteine-250 lowering its pKa and thus conferring high chemical
      reactivity to the mutated residue. We propose that the enhanced reactivity of
      cysteine-250, which is likely to impair the protein function but probably
      insufficient to produce alone a phenotype as a heterozygous S250C variant due to
      compensation mechanisms, might become manifest when combined with other
      genetic/environmental factors. These results can provide the rationale for the
      patient's unusual phenotype, shedding new light into the pathogenesis of the
      clinical association of autoimmunity and immunodeficiency.

PMID- 25068408
TI  - High resolution mapping of modafinil induced changes in glutamate level in rat
      brain.
AB  - Modafinil is marketed in the United States for the treatment of narcolepsy and
      daytime somnolence due to shift-work or sleep apnea. Investigations of this drug
      in the treatment of cocaine and nicotine dependence in addition to disorders of
      executive function are also underway. Modafinil has been known to increase
      glutamate levels in rat brain models. Proton magnetic resonance spectroscopy
      (1HMRS) has been commonly used to detect the glutamate (Glu) changes in vivo. In
      this study, we used a recently described glutamate chemical exchange saturation
      transfer (GluCEST) imaging technique to measure Modafinil induced regional Glu
      changes in rat brain and compared the results with Glu concentration measured by
      single voxel 1HMRS. No increases in either GluCEST maps or 1HMRS were observed
      after Modafinil injection over a period of 5 hours. However, a significant
      increase in GluCEST (19 +/- 4.4%) was observed 24 hours post Modafinil
      administration, which is consistent with results from previous biochemical
      studies. This change was not consistently seen with 1HMRS. GluCEST mapping allows
      regional cerebral Glu changes to be measured and may provide a useful clinical
      biomarker of Modafinil effects for the management of patients with sleep
      disorders and addiction.

PMID- 25068409
TI  - Rule monitoring ability predicts event-based prospective memory performance in
      individuals with TBI.
AB  - Numerous studies have demonstrated that prospective memory (PM) abilities are
      impaired following traumatic brain injury (TBI). PM refers to the ability to
      remember to complete a planned action following a delay. PM post-TBI has been
      shown to be related to performance on neuropsychological tests of executive
      functioning and retrospective episodic memory (RM). However, the relative
      influence of impairments in RM versus executive functioning on PM performance
      post-TBI remains uninvestigated. In the current study, PM and neuropsychological
      test performance were examined in 45 persons with a history of moderate to severe
      TBI at least 1 year before enrollment. Regression analyses examined the relative
      contributions of RM and executive functioning in the prediction of PM performance
      on the Rivermead Behavioral Memory Test (RBMT). Results indicated that scores on
      tests of delayed RM and rule monitoring (i.e., ability to avoid making errors on
      executive measures) were the strongest predictors of PM. When the interaction
      between RM impairment and rule monitoring was examined, a positive relationship
      between PM and rule monitoring was found only in TBI participants with impaired
      RM. Results suggest that PM performance is dependent upon rule monitoring
      abilities only when RM is impaired following TBI.

PMID- 25068410
TI  - HDL and atherosclerosis: Insights from inherited HDL disorders.
AB  - Plasma high density lipoproteins (HDL) comprise a highly heterogeneous family of
      lipoprotein particles, differing in density, size, surface charge, and lipid and
      protein composition. Epidemiological studies have shown that plasma HDL level
      inversely correlates with atherosclerotic cardiovascular disease. The most
      relevant atheroprotective function of HDL is to promote the removal of
      cholesterol from macrophages within the arterial wall and deliver it to the liver
      for excretion in a process called reverse cholesterol transport. In addition,
      HDLs can contribute to the maintenance of endothelial cell homeostasis and have
      potent antioxidant properties. It has been long suggested that individual HDL
      subclasses may differ in terms of their functional properties, but which one is
      the good particle remains to be defined. Inherited HDL disorders are rare
      monogenic diseases due to mutations in genes encoding proteins involved in HDL
      metabolism. These disorders are not only characterized by extremely low or high
      plasma HDL levels but also by an abnormal HDL subclass distribution, and thus
      represent a unique tool to understand the relationship between plasma HDL
      concentration, HDL function, and HDL-mediated atheroprotection. This article is
      part of a Special Issue entitled Linking transcription to physiology in
      lipodomics. 

PMID- 25068411
TI  - Efficacy of ketamine as an adjunct to lidocaine in intravenous regional
      anesthesia.
AB  - BACKGROUND: This study aims to compare and evaluate the effect of adding ketamine
      as an adjunct to lidocaine for intravenous regional anesthesia (IVRA) on
      intraoperative and postoperative analgesia, the onset and recovery times of
      sensory and motor block, and tourniquet pain. METHODS: Forty patients undergoing
      surgery of the hand or forearm under IVRA were randomly assigned to receive
      lidocaine 3 mg/kg (group 1) or lidocaine 3 mg/kg plus ketamine 50 mg (group 2)
      diluted to 40 mL with normal saline. Assessment parameters included the onset and
      recovery times of sensory and motor block, tourniquet pain, intraoperative
      hemodynamics, surgeon and patient satisfaction, postoperative pain, time of first
      analgesic request, total analgesic consumption, and adverse effects in the first
      24 hours postoperatively. RESULTS: Groups 1 and 2 were comparable in demographic
      and surgical parameters. There were no differences between groups in
      intraoperative hemodynamics, onset and recovery times of sensory and motor block,
      or surgeon satisfaction index. Compared with group 1, group 2 patients showed
      less tourniquet pain, prolonged time to first request for postoperative rescue
      analgesia (5.5 +/- 1.3 vs 20.4 +/- 3.7 hours, P < 0.001), lower postoperative
      diclofenac consumption (120.00 +/- 45.23 vs 55.1 +/- 0.00 mg, P < 0.001), lower
      scores for postoperative pain as measured by the Verbal Rating Scale, higher
      patient satisfaction index, and a nonsignificant difference in the incidence of
      postoperative adverse effects between groups. CONCLUSIONS: The addition of
      ketamine to lidocaine in patients receiving IVRA significantly reduced
      intraoperative and postoperative analgesic requirements and improved patient
      satisfaction without causing significant adverse effects.

PMID- 25068412
TI  - Preoperative fascia iliaca compartment block for positioning patients with hip
      fractures for central nervous blockade: a randomized trial.
AB  - BACKGROUND AND OBJECTIVES: Appropriate pain management may positively affect
      outcome following hip fractures. Positioning patients for spinal anesthesia (SA)
      can be extremely painful. Peripheral nerve blockades are gaining popularity in
      this setting. This prospective, randomized study compares the efficacy of fascia
      iliaca compartment block (FICB) to intravenous (IV) fentanyl for positioning hip
      fracture patients for SA. METHODS: Forty-one patients scheduled for hip fracture
      surgery were randomized to receive a bolus dose of IV fentanyl (IVFE) 1.5 MUg/kg
      (IVFE group) or an FICB using 40 mL ropivacaine 0.5% (FICB group) 5 or 20 minutes
      before positioning for SA, respectively. Numeric rating pain scale scores before
      and following the analgesic intervention, time needed and quality of patient
      position for SA performance, postoperative analgesia in terms of time to first IV
      morphine dose demand and morphine consumption during the first 24 hours, and
      patient satisfaction were documented. RESULTS: Compared with the IVFE group, the
      FICB group showed significantly lower numeric rating pain scale scores in all
      instances following the analgesic intervention (P < 0.001), shorter spinal
      performance time (P = 0.001), and better quality of position (P = 0.001).
      Postoperative morphine consumption was lower (P = 0.026), the time to first dose
      demand was longer (P = 0.001), and patient satisfaction rates were higher (P <
      0.001) in the FICB group. CONCLUSIONS: Performing an FICB before positioning for
      SA provides superior pain management compared with IVFE administration,
      facilitates spinal performance, and yields satisfactory postoperative analgesia
      and wide patient acceptance, hence improving overall quality and efficiency of
      care.

PMID- 25068413
TI  - Intraneural or extraneural: diagnostic accuracy of ultrasound assessment for
      localizing low-volume injection.
AB  - BACKGROUND AND OBJECTIVES: When one is performing ultrasound-guided peripheral
      nerve blocks, it is common to inject a small amount of fluid to confirm correct
      placement of the needle tip. If an intraneural needle tip position is detected,
      the needle can then be repositioned to prevent injection of a large amount of
      local anesthetic into the nerve. However, it is unknown if anesthesiologists can
      accurately discriminate intraneural and extraneural injection of small volumes.
      Therefore, this study was conducted to determine the diagnostic accuracy of
      ultrasound assessment using a criterion standard and to compare experts and
      novices in ultrasound-guided regional anesthesia. METHODS: A total of 32
      ultrasound-guided infragluteal sciatic nerve blocks were performed on 21 cadaver
      legs. The injections were targeted to be intraneural (n = 18) or extraneural (n =
      14), and 0.5 mL of methylene blue 1% was injected. Cryosections of the nerve and
      surrounding tissue were assessed by a blinded investigator as "extraneural" or
      "intraneural." Ultrasound video clips of the injections were reviewed by 10
      blinded observers (5 experts, 5 novices) independently who scored each injection
      as either "intraneural," "extraneural," or "undetermined." RESULTS: The mean
      sensitivity of experts and novices was measured to be 0.84 (0.80-0.88) and 0.65
      (0.60-0.71), respectively (P = 0.006), whereas mean specificity was 0.97 (0.94
      0.98) and 0.98 (0.96-0.99) (P = 0.53). CONCLUSIONS: Discrimination of intraneural
      or extraneural needle tip position based on an injection of 0.5mL is possible,
      but even experts missed 1 of 6 intraneural injections. In novices, the
      sensitivity of assessment was significantly lower, highlighting the need for
      focused education.

PMID- 25068414
TI  - Crystal structure of triple-BRCT-domain of ECT2 and insights into the binding
      characteristics to CYK-4.
AB  - Homo sapiens ECT2 is a cell cycle regulator that plays critical roles in
      cytokinesis. ECT2 activity is restrained during interphase via intra-molecular
      interactions that involve its N-terminal triple-BRCT-domain and its C-terminal DH
      PH domain. At anaphase, this self-inhibitory mechanism is relieved by Plk1
      phosphorylated CYK-4, which directly engages the ECT2 BRCT domain. To provide a
      structural perspective for this auto-inhibitory property, we solved the crystal
      structure of the ECT2 triple-BRCT-domain. In addition, we systematically analyzed
      the interaction between the ECT2 BRCT domains with phospho-peptides derived from
      its binding partner CYK-4, and have identified Ser164 as the major phospho
      residue that links CYK-4 to the second ECT2 BRCT domain. 

PMID- 25068416
TI  - Diastereoselective synthesis of fused lactone-pyrrolidinones; application to a
      formal synthesis of (-)-salinosporamide A.
AB  - A mild, diastereoselective synthesis of fused lactone-pyrrolidinones using an
      oxidative radical cyclization is reported. The methodology is demonstrated in a
      formal synthesis of (-)-salinosporamide A. 

PMID- 25068415
TI  - Antimicrobial peptide resistance of Vibrio cholerae results from an LPS
      modification pathway related to nonribosomal peptide synthetases.
AB  - The current pandemic El Tor biotype of O1 Vibrio cholerae is resistant to
      polymyxins, whereas the previous pandemic strain of the classical biotype is
      polymyxin sensitive. The almEFG operon found in El Tor V. cholerae confers >100
      fold resistance to polymyxins through the glycylation of lipopolysaccharide.
      Here, we present the mechanistic determination of initial steps in the AlmEFG
      pathway. We verify that AlmF is an aminoacyl carrier protein and identify AlmE as
      the enzyme required to activate AlmF as a functional carrier protein. A
      combination of structural information and activity assays was used to identify a
      pair of active site residues that are important for mediating AlmE glycine
      specificity. Overall, the structure of AlmE in complex with its glycyl-adenylate
      intermediate reveals that AlmE is related to Gram-positive d-alanine/d-alanyl
      carrier protein ligase, while the trio of proteins in the AlmEFG system forms a
      chemical pathway that resembles the division of labor in nonribosomal peptide
      synthetases. 

PMID- 25068417
TI  - Advance care planning among hematopoietic cell transplant patients and bereaved
      caregivers.
AB  - Younger, healthier patients contemplating high-risk (but potentially curative)
      hematopoietic cell transplants (HCT) may not consider advance care planning
      (ACP). We investigated the effect of pre transplant ACP in surviving HCT patients
      and bereaved caregivers using retrospective, audiotaped telephone surveys.
      Subjects were identified between 2001 and 2003 via databases at two high-volume
      HCT centers. Transcripts were coded by two investigators, with differences
      resolved by consensus. HCT survivors (n=18) were interviewed a median of 13
      months after HCT for acute leukemia (7), lymphoma (5) or other (6); 50% had
      living wills, 72% had a formal proxy. Twelve (67%) had discussed mortality risk
      pre HCT with the medical team. Of those, 92% felt their hope and perception of
      the medical team's truthfulness was increased or unchanged (I/U) by the
      conversation, whereas all felt clinician commitment to transplant was I/U.
      Bereaved caregivers (n=11) were interviewed a median of 10 months post death
      (median 31 days post HCT, range 13-152). Nine (82%) had discussed mortality risk
      pre-HCT with the medical team; 7 (78%) felt hope was I/U, all felt clinician
      commitment to transplant and truthfulness was I/U, and most felt ACP reduced
      burden (67%). ACP discussions with patients and caregivers pre-HCT did not affect
      hope and supported confidence in medical teams. 

PMID- 25068418
TI  - A phase II study of V-BEAM as conditioning regimen before second auto-SCT for
      multiple myeloma.
AB  - High-dose melphalan has been the standard conditioning regimen for auto-SCT in
      multiple myeloma (MM) for decades. A more effective conditioning regimen may
      induce deeper responses and longer remission duration. It is especially needed in
      the setting of second auto-SCT, which rarely achieves comparable results with the
      first auto-SCT using the same conditioning regimen. Here we conducted a phase II
      study to investigate the efficacy and safety of a conditioning regimen V-BEAM
      (bortezomib-BEAM) before second auto-SCT for multiple myeloma. Ten patients were
      enrolled from September 2012 to May 2013. The CR rate at day +100 after auto-SCT
      was 75%; all except for one patient remained in remission after a median follow
      up of 6 months. Three patients developed Clostridium difficile infection. Two
      patients died within the first 30 days of auto-SCT from neutropenic colitis and
      overwhelming sepsis, respectively. Due to the high rate of morbidity and
      mortality, the study was terminated after 10 patients. In summary, although the
      conditioning regimen V-BEAM before second auto-SCT for MM provided promising
      responses, it was associated with unexpected treatment-related toxicity and
      should not be investigated further without modifications. 

PMID- 25068419
TI  - The hematopoietic stem cell transplant comorbidity index can predict for 30-day
      readmission following autologous stem cell transplant for lymphoma and multiple
      myeloma.
AB  - Patients who undergo autologous stem cell transplant (ASCT) for hematologic
      malignancies frequently have multiple comorbidities. The hematopoietic cell
      transplantation comorbidity index (HCT-CI), a transplant-specific modification of
      the Charlson comorbidity index, can predict risk of readmission following
      allogeneic stem cell transplant. Its utility in the autologous setting is
      unknown. We evaluated 620 patients who underwent ASCT at the Ohio State
      University from 2007 to 2012 for lymphoma or multiple myeloma (MM) to identify
      factors associated with readmission. Univariable and multivariable logistic
      regression were used to estimate the odds of readmission within 30 days of
      discharge following ASCT. A Cox proportional hazards model was used to evaluate
      OS. Sixty-four patients were readmitted within 30 days; the most common
      indications were fever and prolonged gastrointestinal toxicity. MM compared with
      lymphoma (odds ratio (OR) 1.89, 95% confidence interval (95% CI): 1.06-3.38,
      P=0.03), HCT-CI?3 (OR 1.74, 95% CI: 1.03-2.96, P=0.04) and length of
      hospitalization ?28 days (OR 3.14, 95% CI: 1.26-7.83, P=0.01) remained
      significantly associated with 30-day readmission in a multivariable model. While
      the model had excellent fit (P>0.75), its ability to predict individual patients
      who would be readmitted was less than acceptable (receiver-operator curve=0.64,
      95% CI: 0.57-0.71). In a multivariable proportional hazards model, 30-day
      readmission (hazards ratio (HR) 1.81, 95% CI: 1.04-3.18, P=0.04), length of
      hospitalization ?28 days (HR 4.93, 95% CI: 2.65-9.18, P<0.001) and
      chemorefractory disease (HR 3.08, 95% CI: 1.74-5.43, P<0.001) were independently
      associated with inferior OS, but HCT-CI was not. Evaluation of other assessment
      tools may allow better prediction of outcomes following ASCT. 

PMID- 25068420
TI  - Hematopoietic SCT for the Black African and non-Black African variants of sickle
      cell anemia.
AB  - Sickle cell anemia (SCA) remains associated with high risks of morbidity and
      early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment
      for SCA. We report our experience with transplantation in a group of patients
      with the non-Black African variant and the Black African variant of SCA. This
      study included 40 consecutive SCA patients (13 patients with the non-Black
      African variant and 27 with the Black African variant) who underwent BM
      transplantation from HLA-identical sibling donors between June 2004 and May 2013,
      following a myeloablative-conditioning regimen. All patients obtained sustained
      engraftment. One patient (non-Black African variant) became a stable mixed
      chimera with 25% donor cells more than 6 years after transplantation. The
      probabilities of survival, SCA-free survival and TRM at 5 years after transplant
      were 91%, 91% and 9%, respectively. All surviving patients remained free of any
      SCA-related events after transplantation. Our results confirm that it is possible
      to offer a greater than 90% chance of cure to children with SCA. HSCT should be
      considered the standard of care for who have an HLA-identical donor, before
      complications result from the sickling of RBC. 

PMID- 25068421
TI  - Improvement of high serum levels of biomarkers of endothelial injury after
      allogeneic hematopoietic SCT with pre-existing severe hepatitis using recombinant
      human soluble thrombomodulin.

PMID- 25068422
TI  - Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary
      syndrome.
AB  - We describe outcomes after allogeneic hematopoietic cell transplantation (HCT)
      for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with
      MF/SS reported to the Center for the International Blood and Marrow Transplant
      from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months
      and most subjects were with multiply relapsed/ refractory disease. The majority
      (64%) received non-myeloablative conditioning (NST) or reduced intensity
      conditioning (RIC). NST/RIC recipients were older in age compared with
      myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in
      recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95%
      confidence interval (CI) 12-27%) and 22% (95% CI 15-31%), respectively. Risk of
      disease progression was 50% (95% CI 41-60%) at 1 year and 61% (95% CI 50-71%) at
      5 years. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%),
      respectively. OS at 1 and 5 years was 54% (95% CI 45-63%) and 32% (95% CI 22
      44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in
      approximately one-third of patients and of those, half remain disease-free. 

PMID- 25068423
TI  - Successful hematopoietic cell transplantation in patients with unique NF-kappaB
      essential modulator (NEMO) mutations.

PMID- 25068424
TI  - Incidence and risk factors for moderate-to-severe veno-occlusive disease of the
      liver after allogeneic stem cell transplantation using a reduced intensity
      conditioning regimen.
AB  - The incidence and outcome of moderate-to-severe veno-occlusive (VOD) disease was
      analyzed in 271 consecutive patients with hematological malignancies who
      underwent allogeneic SCT (allo-SCT) using the same reduced intensity regimen
      (RIC). RIC consisted of fludarabine, BU and antithymocyte globulin (ATG). Twenty
      four out of 271 patients (8.8%) developed VOD, which was severe in only 4 (1.4%)
      out of 24 cases. All four patients with severe VOD finally succumbed to their
      disease. In multivariate analysis, i.v. administration of BU was associated with
      significant reduced incidence of VOD as compared with per os administration. In
      conclusion, VOD remains a serious complication of allo-SCT using RIC regimens
      containing BU. Although the incidence of severe VOD is very low, the overall
      mortality rate in the group of patients with severe VOD remains extremely high
      and therefore novel treatment approaches are needed. 

PMID- 25068425
TI  - Angioedema in patients treated with sirolimus and ACE inhibitor post
      hematopoietic SCT.

PMID- 25068426
TI  - Outcome of invasive mechanical ventilation after pediatric allogeneic
      hematopoietic SCT: results from a prospective, multicenter registry.
AB  - Exact data on prognosis of children receiving invasive mechanical ventilation
      (IMV) after allogeneic hematopoietic SCT (HSCT) is lacking. We therefore started
      a prospective registry in four European university HSCT centers (Leiden, Paris,
      Prague and Utrecht) and their pediatric intensive care units (PICUs). The
      registry started in January 2009. In January 2013, the four centers together had
      treated a total of 83 admissions with IMV. The case fatality rate in these
      patients was 52%. Mortality 6 months after PICU discharge was 45%. There were
      significant differences between centers in the proportion of children who
      received IMV after HSCT (6-23%, P<0.01), in severity of disease on admission to
      PICU (predicted mortality 14-37%, P<0.01), in applying noninvasive ventilation
      before IMV (3-75% of admissions, P<0.01) and in the use of renal replacement
      therapy (RRT) (8-58% of admissions, P<0.01). Severe impairment in oxygenation,
      use of RRT and CMV viremia were independent predictors of mortality. Our study
      shows that mortality in children receiving IMV after HSCT remains high, but has
      clearly improved compared with older studies. Patient selection and treatment in
      PICU differed significantly between centers, which underscores the need to
      standardize and optimize the PICU admission criteria, ventilatory strategies and
      therapies applied in PICU. 

PMID- 25068427
TI  - Sputum cytokine levels in patients undergoing hematopoietic SCT and comparison
      with healthy subjects and COPD: a pilot study.
AB  - Patients undergoing hematopoietic SCT (HSCT) display an airway neutrophilic
      inflammation before transplantation that persists over the years. In this study,
      we have investigated the cytokine profile over a period of 1 year in the sputum
      supernatant of patients who underwent HSCT. We have measured sputum supernatant
      levels of TNF-alpha, TGF-beta1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17 and
      IFN-gamma in 49 HSCT patients and compared the results with those found in 40
      chronic obstructive pulmonary disease (COPD) and 54 healthy subjects matched for
      age. Compared with healthy subjects, before transplantation, HSCT patients
      exhibited raised levels of IL-6 (P<0.001) and IL-8 (P<0.05) while the other
      cytokines were generally poorly detectable. This picture was rather similar to
      that seen in COPD even if cytokine levels were much greater in the latter, with
      IL-8 being significantly greater in COPD than in HSCT patients (P<0.0001). In the
      1 year following transplantation, sputum IL-6 and IL-8 did not differ from those
      in healthy subjects. Overall in HSCT patients, sputum IL-8 and IL-6 correlated
      with sputum neutrophil counts (r=0.4, P<0.0001; r=0.42, P<0.0001, respectively).
      In conclusion, sputum IL-6 and IL-8 may play a role in neutrophilic airway
      inflammation seen in patients undergoing HSCT. 

PMID- 25068428
TI  - Getting fit for allogeneic hematopoietic cell transplantation.

PMID- 25068429
TI  - Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility
      study.
AB  - The feasibility of symptom-limited cardiopulmonary exercise testing (CPET) prior
      to allo-SCT was assessed in addition to the prognostic value of CPET-derived
      measures. CPET was performed prospectively on 21 patients with hematologic
      malignancies, with assessments of peak (for example, peak oxygen consumption,
      VO2peak) and submaximal (for example, ventilatory threshold (VT)) measures of
      cardiopulmonary function. No serious adverse events were observed during CPET
      procedures, with 95% of patients achieving criteria for a peak test. Mean VO2peak
      was 24.7+/-6.4 mL kg(-1 )min(-1) (range: 10.9-35.5), equivalent to 29%+/-17%
      below that of age-matched healthy controls. All patients proceeded with the
      conditioning regimen followed by allo-SCT. Median follow-up was 25 months. During
      this period, 11 (52.4%) patients died (n=6, relapsed disease; n=5, non-relapse
      mortality (NRM)); 9 patients (43%) developed pulmonary toxicity. In univariate
      analyses, both peak and submaximal markers of cardiopulmonary function were
      predictors of OS, pulmonary toxicity and NRM. For OS, the HR for VO2peak and VT
      were 0.89 (95% CI, 0.8-0.99, P=0.04) and 0.84 (95% CI, 0.71-0.98, P=0.03),
      respectively. In conclusion, CPET is safe and feasible prior to allo-SCT.
      Patients have marked impairments in cardiopulmonary function prior to allo-SCT.
      CPET-derived metrics may complement conventional measures to improve risk
      stratification. 

PMID- 25068431
TI  - The ultimate constant of head and neck oncology-the physician-patient
      relationship.
AB  - Head and neck surgeons have the unique opportunity to engage with humans in life
      and death situations. We are confronting cancer, cure, failure, self-image, and
      most of all, a bond with the patient and family. We would like to view our
      expertise in head and neck surgery and the world of caring for our patients much
      like a Brigadoon. However, we daily are confronted with ever-changing and
      evolving approaches to health care that do not involve the physician or the
      patient. What kind of world is healthcare without a physician-patient
      interaction? Yes, there is the government-supported electronic medical record,
      which is here to stay (until our electrical and/or wired network fails). Yes,
      there is new technology, including robotic surgery and telemedicine and efforts
      to link these to our cell phones and applications, making care and expertise more
      available across long distances. And yes, there exist goals to extend care beyond
      the physician to other health care professions as the buffer between the
      physician and the patient, sometimes to reduce cost and sometimes to make care
      more ubiquitous. However, an Internet search will show that most say that the
      only constant in healthcare is change. I propose that the ultimate constant in
      healthcare is the physician-patient relationship. 

PMID- 25068430
TI  - Quality of life and outcomes in patients?60 years of age after allogeneic
      hematopoietic cell transplantation.
AB  - Hematopoietic cell transplantation (HCT) has become an established standard of
      care for many older patients with hematologic malignancies. The effect of
      transplantation on the quality of life (QOL) of older patients, however, has not
      been well studied. We thus analyzed QOL in patients ?60 undergoing an allogeneic
      HCT compared with patients <60 years. Prospective psychometric instruments were
      administered to 351 patients who underwent HCT from 2003 to 2010. Psychometric
      data were assessed longitudinally by validated questionnaires: Functional
      Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), Coping Inventory
      and the Profile of Mood State-Short Form. Patients ?60 reported better social
      (P=0.006) and functional well-being (P=0.05) with FACT assessment, and had better
      total scores, (P=0.043) across all time points. When adjusted for baseline QOL
      scores as a covariate, social well-being remained significantly better, whereas
      the other scores became non-significant. With a median follow-up of 49 months,
      there were no significant differences in OS, relapse-free survival, relapse or
      chronic GVHD. This study provides further evidence that advanced age should not
      be a barrier in the decision to pursue allogeneic HCT. Older patients achieved
      comparable QOL when compared with younger patients. 

PMID- 25068432
TI  - Development of Acanthocheilonema reconditum (Spirurida, Onchocercidae) in the cat
      flea Ctenocephalides felis (Siphonaptera, Pulicidae).
AB  - To investigate larval development of Acanthocheilonema reconditum in the cat flea
      Ctenocephalides felis, fleas were fed through an artificial feeding system with
      dog blood containing different concentrations of microfilariae (i.e. low, group L
      = 250; medium, group M = 500; high, group H = 1500 microfilariae per mL) or no
      microfilariae (group C). Fleas were sampled at 12 different time-points
      throughout the study period (D1-D28) and A. reconditum was detected by
      dissection, PCR and histology. Of 2105 fleas fed with infected dog blood, 891
      (38.7%) died during the study before being sampled whilst the remaining (n =
      1214) were examined for A. reconditum. Upon dissection, first-stage larvae (L1)
      were identified after 2 days post infection (D2), second-stage (L2) at D13 and
      infective third-stage larvae (L3) at D15. Eighteen (30%) of 60 pools of fleas
      molecularly examined tested positive. Histologically, L2 were detected at D13 in
      the sub-cuticle region embedded in the back muscle of one female flea. This study
      provides original data on larval development of A. reconditum in C. felis and
      reports on the usefulness of the artificial feeding system.

PMID- 25068433
TI  - The stereoselective synthesis of alpha-amino aldols starting from terminal
      alkynes.
AB  - A new procedure for the stereoselective synthesis of syn alpha-amino beta-oxy
      ketones is reported. It consists of two steps; in the first step, alpha-amino
      silyl enol ethers having a (Z) geometry are prepared from 1-alkynes via 1
      sulfonyl-1,2,3-triazoles. In the second step, the silyl enol ethers undergo the
      TiCl4-mediated Mukaiyama aldol reaction with aldehydes to produce alpha-amino
      beta-oxy ketones with excellent syn-selectivity. 

PMID- 25068434
TI  - Resilience amongst Australian aboriginal youth: an ecological analysis of factors
      associated with psychosocial functioning in high and low family risk contexts.
AB  - We investigate whether the profile of factors protecting psychosocial functioning
      of high risk exposed Australian Aboriginal youth are the same as those promoting
      psychosocial functioning in low risk exposed youth. Data on 1,021 youth aged 12
      17 years were drawn from the Western Australian Aboriginal Child Health Survey
      (WAACHS 2000-2002), a population representative survey of the health and well
      being of Aboriginal children, their families and community contexts. A person
      centered approach was used to define four groups of youth cross-classified
      according to level of risk exposure (high/low) and psychosocial functioning
      (good/poor). Multivariate logistic regression was used to model the influence of
      individual, family, cultural and community factors on psychosocial outcomes
      separately for youth in high and low family-risk contexts. Results showed that in
      high family risk contexts, prosocial friendship and low area-level socioeconomic
      status uniquely protected psychosocial functioning. However, in low family risk
      contexts the perception of racism increased the likelihood of poor psychosocial
      functioning. For youth in both high and low risk contexts, higher self-esteem and
      self-regulation were associated with good psychosocial functioning although the
      relationship was non-linear. These findings demonstrate that an empirical
      resilience framework of analysis can identify potent protective processes
      operating uniquely in contexts of high risk and is the first to describe distinct
      profiles of risk, protective and promotive factors within high and low risk
      exposed Australian Aboriginal youth. 

PMID- 25068435
TI  - Plasticity and complexity of B cell responses against persisting pathogens.
AB  - Vaccines against acute infections execute their protective effects almost
      exclusively via the induction of antibodies. Development of protective vaccines
      against persisting pathogens lags behind probably because standard immunogens and
      application regimen do not sufficiently stimulate those circuits in B cell
      activation that mediate protection. In general, B cell responses against pathogen
      derived-antigens are generated through complex cellular interactions requiring
      the coordination of innate and adaptive immune mechanisms. In this review, we
      summarize recent findings from prototypic infection models to exemplify how
      generation of protective antibodies against persisting pathogens is imprinted by
      particular pathogen-derived factors and how distinct CD4(+) T cell populations
      determine the quality of these antibodies. Clearly, it is the high plasticity of
      these processes that is instrumental to drive tailored B cell responses that
      protect the host. In sum, application of novel knowledge on B cell plasticity and
      complexity can guide the development of rationally designed vaccines that elicit
      protective antibodies against persisting pathogens. 

PMID- 25068436
TI  - The prevalence and distribution of Th17 and Tc17 cells in patients with thyroid
      tumor.
AB  - Both Th17 and Tc17 cells have been found in various tumors and may play important
      roles in regulating anti-tumor immune responses. However, the prevalence and
      distribution of Th17 and Tc17 cells in thyroid tumors are still unclear. In the
      current study, we examined the percentages of Th17 and Tc17 cells in the
      peripheral blood of 31 thyroid adenoma and 11 thyroid carcinoma patients. The
      serum IL-17 levels were also examined and their associations with Th17 and Tc17
      cells were evaluated. Moreover, the presence of Th17 cells was detected in both
      thyroid adenoma and carcinoma patients. Our results showed that compared with
      healthy individuals, patients with thyroid tumors had a higher proportion of Th17
      and lower proportion of Tc17 cells in peripheral blood. The serum concentration
      of IL-17 was significantly increased in patients with thyroid tumors and it was
      correlated with the percent of Th17 cells. Furthermore, the number of Th17 cells
      was significantly increased in the tumors of the patients. Th17 and Tc17 cells
      were negatively correlated with the tumor size. There was no significant
      difference between thyroid adenoma and carcinoma patients. These results indicate
      that Th17 cells may contribute to thyroid tumor pathogenesis. 

PMID- 25068437
TI  - Bariatric surgery: an attractive therapeutic modality for type 2 diabetes
      mellitus.

PMID- 25068438
TI  - Theoretical studies on kinetics, mechanism and thermochemistry of gas-phase
      reactions of HFE-449mec-f with OH radicals and Cl atom.
AB  - A theoretical study on the mechanism and kinetics of the gas phase reactions of
      CF3CHFCF2OCH2CF3 (HFE-449mec-f) with the OH radicals and Cl atom have been
      performed using meta-hybrid modern density functional M06-2X using 6-31+G(d,p)
      basis set. Two conformers have been identified for CF3CHFCF2OCH2CF3 and the most
      stable one is considered for detailed study. Reaction profiles for OH-initiated
      hydrogen abstraction are modeled including the formation of pre-reactive and post
      reactive complexes at entrance and exit channels. Our calculations reveal that
      hydrogen abstraction from the CH2 group is thermodynamically and kinetically more
      facile than that from the CHF group. Using group-balanced isodesmic reactions,
      the standard enthalpies of formation for HFE-449mecf and radicals generated by
      hydrogen abstraction, are also reported. The calculated bond dissociation
      energies for CH bonds are in good agreement with experimental results. The rate
      constants of the two reactions are determined for the first time in a wide
      temperature range of 250-450K. The calculated rate constant values are found to
      be 9.10*10(-15) and 4.77*10(-17)cm(3)molecule(-1)s(-1) for reactions with OH
      radicals and Cl atom, respectively. At 298K, the total calculated rate
      coefficient for reactions with OH radical is in good agreement with the
      experimental results. The atmospheric life time of HFE-449mec-f is estimated to
      be 0.287 years. 

PMID- 25068439
TI  - Interaction energy analysis on specific binding of influenza virus hemagglutinin
      to avian and human sialosaccharide receptors: importance of mutation-induced
      structural change.
AB  - On the basis of available molecular structures registered in Protein Data Bank,
      we have theoretically carried out the interaction energy analysis for the
      complexes of influenza virus hemagglutinin (HA) proteins and sialosaccharide
      receptor analogs of host cells. Employing the fragment molecular orbital method
      for quantum-chemical calculations, the differences in magnitude and pattern of
      the interactions between the amino acid residues of avian-type (H7N3) or human
      type (H7N9) HA and each saccharide part of avian or human receptor were studied
      in order to elucidate the molecular mechanism of avian-to-human infectious
      transmission of influenza virus. We have thus confirmed quantitatively that the
      mutations from the avian HA to the human HA significantly strengthened the
      binding affinity of human HA to human receptor, while retaining the affinity to
      avian receptor. In addition to direct effects regarding the changes of
      interactions between the altered residues and the receptors, we have also found
      the importance of indirect effects in which structural changes caused by the
      mutations play vital roles to modify the intermolecular interactions. 

PMID- 25068440
TI  - A collaborative visual analytics suite for protein folding research.
AB  - Molecular dynamics (MD) simulation is a crucial tool for understanding principles
      behind important biochemical processes such as protein folding and molecular
      interaction. With the rapidly increasing power of modern computers, large-scale
      MD simulation experiments can be performed regularly, generating huge amounts of
      MD data. An important question is how to analyze and interpret such massive and
      complex data. One of the (many) challenges involved in analyzing MD simulation
      data computationally is the high-dimensionality of such data. Given a massive
      collection of molecular conformations, researchers typically need to rely on
      their expertise and prior domain knowledge in order to retrieve certain
      conformations of interest. It is not easy to make and test hypotheses as the data
      set as a whole is somewhat "invisible" due to its high dimensionality. In other
      words, it is hard to directly access and examine individual conformations from a
      sea of molecular structures, and to further explore the entire data set. There is
      also no easy and convenient way to obtain a global view of the data or its
      various modalities of biochemical information. To this end, we present an
      interactive, collaborative visual analytics tool for exploring massive, high
      dimensional molecular dynamics simulation data sets. The most important utility
      of our tool is to provide a platform where researchers can easily and effectively
      navigate through the otherwise "invisible" simulation data sets, exploring and
      examining molecular conformations both as a whole and at individual levels. The
      visualization is based on the concept of a topological landscape, which is a 2D
      terrain metaphor preserving certain topological and geometric properties of the
      high dimensional protein energy landscape. In addition to facilitating easy
      exploration of conformations, this 2D terrain metaphor also provides a platform
      where researchers can visualize and analyze various properties (such as contact
      density) overlayed on the top of the 2D terrain. Finally, the software provides a
      collaborative environment where multiple researchers can assemble observations
      and biochemical events into storyboards and share them in real time over the
      Internet via a client-server architecture. The software is written in Scala and
      runs on the cross-platform Java Virtual Machine. Binaries and source code are
      available at http://www.aylasoftware.org and have been released under the GNU
      General Public License. 

PMID- 25068441
TI  - Ferroplasmons: intense localized surface plasmons in metal-ferromagnetic
      nanoparticles.
AB  - Interaction of photons with matter at length scales far below their wavelengths
      has given rise to many novel phenomena, including localized surface plasmon
      resonance (LSPR). However, LSPR with narrow bandwidth (BW) is observed only in a
      select few noble metals, and ferromagnets are not among them. Here, we report the
      discovery of LSPR in ferromagnetic Co and CoFe alloy (8% Fe) in contact with Ag
      in the form of bimetallic nanoparticles prepared by pulsed laser dewetting. These
      plasmons in metal-ferromagnetic nanostructures, or ferroplasmons (FP) for short,
      are in the visible spectrum with comparable intensity and BW to those of the
      LSPRs from the Ag regions. This finding was enabled by electron energy-loss
      mapping across individual nanoparticles in a monochromated scanning transmission
      electron microscope. The appearance of the FP is likely due to plasmonic
      interaction between the contacting Ag and Co nanoparticles. Since there is no
      previous evidence for materials that simultaneously show ferromagnetism and such
      intense LSPRs, this discovery may lead to the design of improved plasmonic
      materials and applications. It also demonstrates that materials with interesting
      plasmonic properties can be synthesized using bimetallic nanostructures in
      contact with each other. 

PMID- 25068442
TI  - Analysis of S100 calcium binding protein B serum levels in different types of
      traumatic intracranial lesions.
AB  - The objective of this study was to determine whether the type of intracranial
      traumatic lesions, the number of simultaneous traumatic lesions, and the
      occurrence of skull and facial bone fractures have an influence on S100 calcium
      binding protein B (S100B) serum levels. Patients with blunt traumatic brain
      injury were prospectively enrolled into this cohort study over a period of 13
      months. Venous blood samples were obtained prior to emergency cranial CT scan in
      all patients within 3 h after injury. The patients were then assigned into six
      groups: 1) concussion, 2) epidural hematoma, 3) subdural hematoma, 4)
      subarachnoid hemorrhage, 5) brain contusions, and 6) brain edema. The study
      included 1696 head trauma patients with a mean age of 57.7 +/- 25.3 years, and
      126 patients (8%) had 182 traumatic lesions on CT. Significant differences in
      S100B serum levels were found between cerebral edema and the other four bleeding
      groups: epidural p = 0.0002, subdural p < 0.0001, subarachnoid p = 0.0001, brain
      contusions p = 0.0003, and concussion p < 0.0001. Significant differences in
      S100B values between patients with one or two intracranial lesions (p = 0.014) or
      with three (p < 0.0001) simultaneous intracranial lesions were found. In patients
      with intracranial traumatic lesions, skull fractures, as well as skull and facial
      bone fractures occurring together, were identified as significant additional
      factors for the increase in serum S100B levels (p < 0.0001). Older age was also
      associated with elevated S100B serum levels (p < 0.0001). Our data show that peak
      S100B serum levels were found in patients with cerebral edema and brain
      contusions.

PMID- 25068443
TI  - The exposure to coarse, fine and ultrafine particle emissions from concrete
      mixing, drilling and cutting activities.
AB  - Building activities generate coarse (PM10<=10MUm), fine (PM2.5<=2.5MUm) and
      ultrafine particles (<100nm) making it necessary to understand both the exposure
      levels of operatives on site and the dispersion of ultrafine particles into the
      surrounding environment. This study investigates the release of particulate
      matter, including ultrafine particles, during the mixing of fresh concrete
      (incorporating Portland cement with Ground Granulated Blastfurnace Slag, GGBS or
      Pulverised Fuel Ash, PFA) and the subsequent drilling and cutting of hardened
      concrete. Particles were measured in the 5-10,000nm size range using a GRIMM
      particle spectrometer and a fast response differential mobility spectrometer
      (DMS50). The mass concentrations of PM2.5-10 fraction contributed ~52-64% of
      total mass released. The ultrafine particles dominated the total particle number
      concentrations (PNCs); being 74, 82, 95 and 97% for mixing with GGBS, mixing with
      PFA, drilling and cutting, respectively. Peak values measured during the drilling
      and cutting activities were 4 and 14 times the background. Equivalent emission
      factors were calculated and the total respiratory deposition dose rates for PNCs
      for drilling and cutting were 32.97+/-9.41*10(8)min(-1) and 88.25+/
      58.82*10(8)min(-1). These are a step towards establishing number and mass
      emission inventories for particle exposure during construction activities. 

PMID- 25068444
TI  - Endogenous thrombin potential in Behcet's disease: relationship with thrombosis
      and anticoagulant therapy.
AB  - OBJECTIVES: To analyse the relationship between an automated thrombin generation
      test, the endogenous thrombin potential (ETP), and other hypercoagulability
      markers, with vascular involvement in patients with Behcet's disease (BD).
      Patients and methods. We analysed 56 BD patients (30 men; mean age, 34.4 +/- 14.3
      years) without any known thrombophilic factor, of which 17 had previously
      suffered from thrombosis (deep venous thrombosis in 14 and ischaemic stroke in
      3), and 56 controls matched for age and sex. Additionally, we also evaluated 20
      plasma samples with an international normalised ratio (INR) between 1.5 and 5.0
      obtained from patients with atrial fibrillation but without a history of embolic
      events that were under treatment with acenocumarol. Thrombin generation was
      measured as ETP with a chromogenic assay in an automated analyser. Factor VIII,
      von Willebrand factor antigen, prothrombin fragment 1.2, D-dimer and plasmin
      antiplasmin complexes were also measured. RESULTS: BD patients showed higher ETP
      values than controls (471.3+/- 49.3 vs. 427.5+/- 31.3 mA; p<0.001). Additionally,
      BD patients with a history of thrombosis had higher ETP values than patients
      without thrombosis (496.6+/- 36.5 vs. 460.7+/- 50.5 mA; p<0.01). Factor VIII and
      von Willebrand factor antigen were also elevated in BD patients, but only von
      Willebrand factor antigen showed statistically significant differences between BD
      patients with and without thrombosis. Acenocumarol treatment reduced thrombin
      generation in BD patients in parallel to INR levels, reaching values similar to
      those of patients with atrial fibrillation and similar INR. CONCLUSIONS: BD is
      associated with thrombosis, and increased thrombin generation (measured as ETP)
      is a promising marker of hypercoagulability.

PMID- 25068445
TI  - Adsorption of small hydrocarbons on the three-fold PdGa surfaces: the road to
      selective hydrogenation.
AB  - Intermetallic compounds are a promising class of materials as stable and
      selective heterogeneous catalysts. Here, the (111) and (-1-1-1) single crystal
      surfaces of the PdGa intermetallic compound were studied as model catalysts with
      regard to the selective hydrogenation of acetylene (C2H2) to ethylene (C2H4). The
      distinct atomic surface structures exhibit isolated active centers of single
      atomic and three atomic Pd ensembles, respectively. For the two prototypal model
      catalyst surfaces, the adsorption sites and configurations for hydrogen (H2),
      acetylene, and ethylene were investigated by combining scanning tunneling
      microscopy, temperature-programmed desorption, and ab initio modeling. The
      topmost Pd surface atoms provide the preferred adsorption sites for all studied
      molecules. The structural difference of the Pd ensembles has a significant
      influence on the adsorption energy and configuration of C2H2, while the influence
      of the ensemble structure is weak for C2H4 and H2 adsorption. To approach the
      question of catalytic performance, we simulated the reaction pathways for the
      heterogeneous catalytic hydrogenation of acetylene on the two surfaces by means
      of density functional theory. Due to the geometrical separation of the Pd sites
      on the surfaces, the steric approach of the reactants (H and C2Hx) was found to
      be of importance to the energetics of the reaction. The presented study gives a
      direct comparison of binding properties of catalytic Pd on-top sites vs three
      fold Pd hollow sites and is therefore of major relevance to the knowledge-based
      design of highly selective hydrogenation catalysts. 

PMID- 25068447
TI  - Electrochemistry and catalytic properties for dioxygen reduction using ferrocene
      substituted cobalt porphyrins.
AB  - Cobalt porphyrins having 0-4 meso-substituted ferrocenyl groups were synthesized
      and examined as to their electrochemical properties in N,N'-dimethylformamide
      (DMF) containing 0.1 M tetra-n-butylammonium perchlorate as a supporting
      electrolyte. The examined compounds are represented as (Fc)n(CH3Ph)(4-n)PorCo,
      where Por is a dianion of the substituted porphyrin, Fc and CH3Ph represent
      ferrocenyl and/or p-CH3C6H4 groups linked at the four meso-positions of the
      macrocycle, and n varies from 0 to 4. Each porphyrin undergoes two reversible one
      electron reductions and two to six one-electron oxidations in DMF, with the exact
      number depending upon the number of Fc groups on the compound. The first electron
      addition is metal-centered to generate a Co(I) porphyrin. The second is porphyrin
      ring-centered and leads to formation of a Co(I) pi-anion radical. The first
      oxidation of each Co(II) porphyrin is metal-centered to generate a Co(III)
      derivative under the given solution conditions. Each ferrocenyl substituent can
      also be oxidized by one electron, and this occurs at more positive potentials.
      Each compound was investigated as a catalyst for the electoreduction of dioxygen
      when adsorbed on a graphite electrode in 1.0 M HClO4. The number of electrons
      transferred (n) during the catalytic reduction was 2.0 for the three ferrocenyl
      substituted compounds, consistent with only H2O2 being produced as a product of
      the reaction. Most monomeric cobalt porphyrins exhibit n values between 2.6 and
      3.1 under the same solution conditions, giving a mixture of H2O and H2O2 as a
      reduction product, although some monomeric porphyrins can give an n value of 4.0.
      Our results in the current study indicate that appending ferrocene groups
      directly to the meso positions of a porphyrin macrocycle will increase the
      selectivity of the oxygen reduction, resulting in formation of only H2O2 as a
      reaction product. This selectivity of the electrocatalytic oxygen reduction
      reaction is explained on the basis of steric hindrance by the ferrocene
      substituents which prevent dimerization.

PMID- 25068446
TI  - A new ion mobility-linear ion trap instrument for complex mixture analysis.
AB  - A new instrument that couples a low-pressure drift tube with a linear ion trap
      mass spectrometer is demonstrated for complex mixture analysis. The combination
      of the low-pressure separation with the ion trapping capabilities provides
      several benefits for complex mixture analysis. These include high sensitivity,
      unique ion fragmentation capabilities, and high reproducibility. Even though the
      gas-phase separation and the mass measurement steps are each conducted in an ion
      filtering mode, detection limits for mobility-selected peptide ions are in the
      tens of attomole range. In addition to ion separation, the low-pressure drift
      tube can be used as an ion fragmentation cell yielding mobility-resolved fragment
      ions that can be subsequently analyzed by multistage tandem mass spectrometry
      (MS(n)) methods in the ion trap. Because of the ion trap configuration, these
      methods can be comprised of any number (limited by ion signal) of collision
      induced dissociation (CID) and electron transfer dissociation (ETD) processes.
      The high reproducibility of the gas-phase separation allows for comparison of two
      dimensional ion mobility spectrometry (IMS)-MS data sets in a pixel-by-pixel
      fashion without the need for data set alignment. These advantages are presented
      in model analyses representing mixtures encountered in proteomics and
      metabolomics experiments. 

PMID- 25068448
TI  - Decreased circulating visfatin is associated with improved disease activity in
      early rheumatoid arthritis: data from the PERAC cohort.
AB  - OBJECTIVE: To evaluate circulating visfatin and its relationship with disease
      activity and serum lipids in patients with early, treatment-naive rheumatoid
      arthritis (RA). METHODS: Serum visfatin was measured in 40 patients with early RA
      before and after three months of treatment and in 30 age- and sex-matched healthy
      individuals. Disease activity was assessed using the Disease Activity Score for
      28 joints (DAS28) at baseline and at three and 12 months. Multivariate linear
      regression analysis was performed to evaluate whether improved disease activity
      is related to serum visfatin or a change in visfatin level. RESULTS: Serum
      visfatin was significantly elevated in early RA patients compared to healthy
      controls (1.92+/-1.17 vs. 1.36+/-0.93 ng/ml; p = 0.034) and significantly
      decreased after three months of treatment (to 0.99+/-0.67 ng/ml; p<0.001).
      Circulating visfatin and a change in visfatin level correlated with disease
      activity and improved disease activity over time, respectively. A decrease in
      visfatin after three months predicted a DAS28 improvement after 12 months. In
      addition, decreased serum visfatin was not associated with an improved
      atherogenic index but was associated with an increase in total cholesterol level.
      CONCLUSION: A short-term decrease in circulating visfatin may represent an
      independent predictor of long-term disease activity improvement in patients with
      early RA.

PMID- 25068450
TI  - Lateral growth of ZnO nanorod arrays in polyhedral structures for high on-current
      field-effect transistors.
AB  - Lateral growth of one-dimensional nanostructures is crucial for high performance
      field-effect transistors (FETs) which can drive a high on-current that is
      proportional to the number of nanorods (NRs) aligned between electrodes. Hence,
      it is strongly required to laterally and directly grow a large number of NRs
      between electrodes. For the first time, we propose a polyhedral-type FET (PH-FET)
      based on laterally-grown ZnO NRs, which includes circle, square and triangle
      configurations. The PH-FET structure not only provides a larger contact area than
      that of the planar parallel-type FET so that a great number of ZnO NRs are
      aligned between electrodes, but also generates a high on-current in the mA range
      (i.e., 5.5-6.8 mA). The high on-current PH-FET opens up a new range of
      applications for power devices where large currents have to be switched. 

PMID- 25068449
TI  - Gene expression profiling reveals similarities between the spatial architectures
      of postnatal articular and growth plate cartilage.
AB  - Articular and growth plate cartilage are discrete tissues but arise from a common
      cartilaginous condensation and have comparable spatial architectures consisting
      of distinct layers of chondrocytes. To investigate similarities and differences
      between articular and growth plate cartilage and to explore transcriptional
      changes that occur during the onset of their divergence, we performed manual
      microdissection of 10-day-old rat proximal tibias, microarray analysis,
      bioinformatics, and real-time PCR to compare gene expression profiles in
      individual cartilage layers. We found that many genes that were spatially
      upregulated in the intermediate/deep zone of articular cartilage were also
      spatially upregulated in the resting zone of growth plate cartilage (overlap
      greater than expected by chance, P<0.001). Interestingly, the superficial zone of
      articular cartilage showed an expression profile with similarities to both the
      proliferative and hypertrophic zones of growth plate cartilage (P<0.001 each).
      Additionally, significant numbers of known proliferative zone markers (3 out of
      6) and hypertrophic zone markers (27 out of 126) were spatially upregulated in
      the superficial zone (more than expected by chance, P<0.001 each). In conclusion,
      we provide evidence that the intermediate/deep zone of articular cartilage has a
      gene expression profile more similar to that of the resting zone of growth plate
      cartilage, whereas the superficial zone has a gene expression profile more
      similar to those of the proliferative and hypertrophic zones. These findings
      suggest that the superficial zone chondrocytes of articular cartilage
      differentiate according to a program that is not completely different from but
      instead has distinct similarities to the hypertrophic differentiation program of
      growth plate chondrocytes. We also present functional signaling pathways
      implicated by differential gene expression between articular and growth plate
      cartilage during their initial separation by the secondary ossification center. 

PMID- 25068451
TI  - Effects of cholesterol concentration on the interaction of cytarabine with lipid
      membranes: a molecular dynamics simulation study.
AB  - Liposomal cytarabine, DepoCyt, is a chemotherapy agent which is used in cancer
      treatment. This form of cytarabine has more efficacy and fewer side effects
      relative to the other forms. Since DepoCyt contains the cytarabine encapsulated
      within phosphatidylcholine and the sterol molecules, we modeled
      dioleoylphosphatidylcholine (DOPC)/cholesterol bilayer membrane as a carrier for
      cytarabine to study drug-bilayer interactions. For this purpose, we performed a
      series of united-atom molecular dynamics (MD) simulations for 25 ns to
      investigate the interactions between cytarabine and cholesterol-containing DOPC
      lipid bilayers. Only the uncharged form of cytarabine molecule was investigated.
      In this study, different levels of the cholesterol content (0, 20, and 40%) were
      used. MD simulations allowed us to determine dynamical and structural properties
      of the bilayer membrane and to estimate the preferred location and orientation of
      the cytarabine molecule inside the bilayer membrane. Properties such as membrane
      thickness, area per lipid, diffusion coefficient, mass density, bilayer packing,
      order parameters, and intermolecular interactions were examined. The results show
      that by increasing the cholesterol concentration in the lipid bilayers, the
      bilayer thickness increases and area per lipid decreases. Moreover, in accordance
      with the experiments, our calculations show that cholesterol molecules have
      ordering effect on the hydrocarbon acyl chains. Furthermore, the cytarabine
      molecule preferentially occupies the polar region of the lipid head groups to
      form specific interactions (hydrogen bonds). Our results fully support the
      experimental data. Our finding about drug-bilayer interaction is crucial for the
      liposomal drug design.

PMID- 25068452
TI  - Randomized controlled trial of cognitive behavioral stress management in breast
      cancer: a brief report of effects on 5-year depressive symptoms.
AB  - OBJECTIVE: Survivors of breast cancer experience stress and are at risk for
      depressive symptoms following primary treatment. Group-based interventions such
      as cognitive-behavioral stress management (CBSM) delivered postsurgery for
      nonmetastatic breast cancer (BCa) were previously associated with fewer
      depressive symptoms over a 12-month follow-up; few studies have examined the
      longer-term benefits of such psychosocial interventions. This 5-year follow-up
      study of a previously conducted trial (#NCT01422551) tested whether group-based
      CBSM following surgery for nonmetastatic BCa was associated with fewer depressive
      symptoms. METHODS: Women (N = 240) with Stage 0-IIIb BCa were recruited 2-10
      weeks postsurgery and randomized to a 10-week CBSM intervention group or a 1-day
      psycho-educational control group. Women were recontacted 5 years poststudy
      enrollment and reconsented to participate in the follow-up study (N = 130).
      Depressive symptomatology was assessed using the Center for Epidemiologic Studies
      Depression scale (CES-D). ANOVA and ANCOVA analyses were employed to test for
      group differences on the CES-D at 5-year follow-up accounting for relevant
      covariates. RESULTS: Participants assigned to CBSM reported significantly fewer
      depressive symptoms (M = 9.99, SE = 0.93) at the follow-up compared with those in
      the control group (M = 12.97, SE = 0.99), p = .030. With covariates, the group
      difference remained significant, p = .012. CONCLUSION: Women who received CBSM
      postsurgery for BCa reported fewer depressive symptoms than those in the control
      group in this 5-year follow-up. Psychosocial interventions early in treatment may
      influence long-term psychological well-being in BCa survivors.

PMID- 25068453
TI  - Daily self-disclosure and sleep in couples.
AB  - OBJECTIVE: An emerging literature provides evidence for the association between
      romantic relationship quality and sleep, an important factor in health and well
      being. However, we still know very little about the specific relationship
      processes that affect sleep behavior. Therefore, the goal of this study was to
      examine how self-disclosure, an important relational process linked to intimacy,
      relationship satisfaction, and health, is associated with sleep behavior. METHOD:
      As part of a larger study of family processes, wives (n = 46) and husbands (n =
      38) from 46 cohabiting families completed 56 days of daily diaries. Spouses
      completed evening diaries assessing daily self-disclosure, relationship
      satisfaction, and mood and morning diaries assessing the prior night's sleep.
      Multilevel modeling was used to explore the effects of both daily variation in
      and average levels across the 56 days of self-disclosure on sleep. RESULTS: Daily
      variation in self-disclosure predicted sleep outcomes for wives, but not for
      husbands. On days when wives self-disclosed more to their spouses than their
      average level, their subjective sleep quality and sleep efficiency that night
      improved. Furthermore, daily self-disclosure buffered the effect of high negative
      mood on sleep latency for wives, but not husbands. In contrast, higher average
      levels of self-disclosure predicted less waking during the night for husbands,
      but not for wives. CONCLUSION: The association between self-disclosure and sleep
      is one mechanism by which daily relationship functioning may influence health and
      well-being. Gender may play a role in how self-disclosure is associated with
      sleep.

PMID- 25068454
TI  - Marital quality and diabetes: results from the Health and Retirement Study.
AB  - OBJECTIVE: Poor marital quality is associated with many different indicators of
      poor health, including immunologic and metabolic responses that have relevance
      for distal disease outcomes such as diabetes. We conducted this study to evaluate
      whether poor marital quality was associated with the prevalence of diabetes in a
      population-based sample of Americans over the age of 50. METHOD: Participants
      were married adults from the 2006 (N = 3,898) and 2008 (N = 3,452) waves of the
      Health and Retirement Study. Participants completed an interview and a self
      report questionnaire, and current use of diabetes medication and glycosylated
      hemoglobin obtained from blood spot samples were used to index diabetes status.
      Marital quality was assessed with items regarding perceived frequency of positive
      and negative exchanges with partner. RESULTS: Decreasing frequency of positive
      exchanges and increasing frequency of negative exchanges with one's spouse were
      associated with higher prevalence of diabetes among men, but not women at both
      waves; gender significantly moderated the associations between partner exchanges
      and diabetes status for the 2006 data. The association between frequency of
      partner exchanges and diabetes status generally remained significant in men after
      accounting for demographic characteristics and other risk factors (obesity,
      hypertension, low physical activity). CONCLUSION: Poor marital quality as
      operationalized by rates of positive and negative partner exchanges was
      associated with increased prevalence of diabetes in men. These results are
      consistent with prior work on marriage and health, and suggest that poor marital
      quality may be a unique risk factor for diabetes.

PMID- 25068455
TI  - Children and adolescents coping with cancer: self- and parent reports of coping
      and anxiety/depression.
AB  - OBJECTIVE: The diagnosis and treatment of cancer present children and adolescents
      with significant stress. However, research on the ways that children and
      adolescents cope with cancer-related stress has not yielded clear findings on the
      efficacy of different coping strategies, and has been limited by reliance
      primarily on self-reports of both coping and distress. To address this gap, the
      current study used a control-based model of coping to examine self- and parent
      reports of child/adolescent coping and symptoms of anxiety and depression in a
      sample of children with cancer. METHOD: Children and adolescents (5 to 17 years
      old) and their parents were recruited near the time of a child's diagnosis or
      relapse of cancer (M = 1.30 months postdiagnosis). Child self-reports (n = 153),
      mother reports (n = 297), and father reports (n = 161) of children's coping and
      symptoms of anxiety/depression were obtained. RESULTS: Bivariate correlations
      revealed significant associations for secondary control coping (efforts to adapt
      to source of stress; e.g., acceptance, cognitive reappraisal) and disengagement
      coping (e.g., avoidance, denial) with anxiety/depression within and across
      informants. Linear multiple regression analyses indicated that secondary control
      coping accounted for unique variance in symptoms of anxiety/depression both
      within and across informants. CONCLUSIONS: Secondary control coping appears
      important for children and adolescents during early phases of treatment for
      cancer, and it may serve as an important target for future interventions to
      enhance adjustment in these children.

PMID- 25068456
TI  - Associations of weight stigma with cortisol and oxidative stress independent of
      adiposity.
AB  - OBJECTIVE: Weight discrimination is associated with increased risk of obesity.
      The mechanism of this relationship is unknown, but being overweight is a highly
      stigmatized condition and may be a source of chronic stress that contributes to
      the development and pathophysiology of obesity. The objective of this study was
      to test whether weight stigma is associated with physiological risk factors
      linked to stress and obesity, including hypercortisolism and oxidative stress,
      independent of adiposity. METHOD: We examined the frequency of experiencing
      situations involving weight stigma and consciousness of weight stigma in relation
      to hypothalamic--pituitary--adrenal axis activity and oxidative stress (F2
      isoprostanes) in 45 healthy overweight to obese women. RESULTS: Independent of
      abdominal fat, weight stigma was significantly related to measures of cortisol
      (including salivary measures of cortisol awakening response and serum morning
      levels) as well as higher levels of oxidative stress. Perceived stress mediated
      the relationship between weight stigma consciousness and the cortisol awakening
      response. CONCLUSION: These preliminary findings show that weight stigma is
      associated with greater biochemical stress, independent of level of adiposity. It
      is possible that weight stigma may contribute to poor health underlying some
      forms of obesity.

PMID- 25068459
TI  - Photochemistry of matrix isolated (trifluoromethyl)sulfonyl azide, CF3SO2N3.
AB  - The photochemistry of matrix isolated (trifluoromethylsulfonyl) azide, CF3SO2N3,
      has been studied at low temperatures. Upon ArF laser irradiation (lambda = 193
      nm), the azide eliminates N2 and furnishes triplet
      [(trifluoromethyl)sulfonyl]nitrene, CF3SO2N, which has been characterized by IR
      and EPR spectroscopy. Upon subsequent UV light irradiation (lambda = 260-400 nm)
      the nitrene converts to CF3N?SO2 and CF3S(O)NO through a Curtius-type
      rearrangement. Further two new species CF2N?SO2F and FSNO were identified
      together with CF2NF, SO2, F2CO, CF3NO, and SO as side products. In addition,
      triplet nitrene CF3N was detected by its EPR and IR spectra. The complex stepwise
      photodecomposition of matrix isolated CF3SO2N3 is discussed in terms of the
      observed photolysis products and quantum chemical calculations. 

PMID- 25068458
TI  - Prenatal exposure to maternal bereavement and childbirths in the offspring: a
      population-based cohort study.
AB  - INTRODUCTION: The decline in birth rates is a concern in public health. Fertility
      is partly determined before birth by the intrauterine environment and prenatal
      exposure to maternal stress could, through hormonal disturbance, play a role.
      There has been such evidence from animal studies but not from humans. We aimed to
      examine the association between prenatal stress due to maternal bereavement
      following the death of a relative and childbirths in the offspring. MATERIALS AND
      METHODS: This population-based cohort study included all subjects born in Denmark
      after 1968 and in Sweden after 1973 and follow-up started at the age of 12 years.
      Subjects were categorized as exposed if their mothers lost a close relative
      during pregnancy or the year before and unexposed otherwise. The main outcomes
      were age at first child and age-specific mean numbers of childbirths. Data was
      analyzed using Cox Proportional Hazards models stratified by gender and adjusted
      for several covariates. Subanalyses were performed considering the type of
      relative deceased and timing of bereavement. RESULTS: A total of 4,121,596
      subjects were followed-up until up to 41 years of age. Of these subjects, 93,635
      (2.3%) were exposed and 981,989 (23.8%) had at least one child during follow-up
      time. Compared to unexposed, the hazard ratio (HR) [95% confidence interval] of
      having at least one child for exposed males and females were 0.98 [0.96-1.01] and
      1.01 [0.98-1.03], respectively. We found a slightly reduced probability of having
      children in females born to mothers who lost a parent with HR = 0.97 [0.94-0.99]
      and increased probability in females born to mothers who lost another child (HR =
      1.09 [1.04-1.14]), the spouse (HR = 1.29 [1.12-1.48]) or a sibling (HR = 1.13
      [1.01-1.27]). CONCLUSIONS: Our results suggested no overall association between
      prenatal exposure to maternal stress and having a child in early adulthood but a
      longer time of follow-up is necessary in order to reach a firmer conclusion.

PMID- 25068457
TI  - Sonic hedgehog signaling in the lung. From development to disease.
AB  - Over the past two decades, the secreted protein sonic hedgehog (SHH) has emerged
      as a critical morphogen during embryonic lung development, regulating the
      interaction between epithelial and mesenchymal cell populations in the airway and
      alveolar compartments. There is increasing evidence that the SHH pathway is
      active in adult lung diseases such as pulmonary fibrosis, asthma, chronic
      obstructive pulmonary disease, and lung cancer, which raises two questions: (1)
      What role does SHH signaling play in these diseases? and (2) Is it a primary
      driver of the disease or a response (perhaps beneficial) to the primary
      disturbance? In this review we aim to fill the gap between the well-studied
      period of embryonic lung development and the adult diseased lung by reviewing the
      hedgehog (HH) pathway during the postnatal period and in adult uninjured and
      injured lungs. We elucidate the similarities and differences in the epithelial
      mesenchymal interplay during the fibrosis response to injury in lung compared
      with other organs and present a critical appraisal of tools and agents available
      to evaluate HH signaling. 

PMID- 25068461
TI  - Utility of 30 and 60 minute cortisol samples after high-dose synthetic ACTH-1-24
      injection in the diagnosis of adrenal insufficiency.
AB  - BACKGROUND: In clinical practise the high dose ACTH stimulation test (HDT) is
      frequently used in the assessment of adrenal insufficiency (AI). However, there
      is uncertainty regarding optimal time-points and number of blood samplings. The
      present study compared the utility of a single cortisol value taken either 30 or
      60 minutes after ACTH stimulation with the traditional interpretation of the HDT.
      METHODS: Retrospective analysis of 73 HDT performed at a single tertiary
      endocrine centre. Serum cortisol was measured at baseline, 30 and 60 minutes
      after intravenous administration of 250 ug synthetic ACTH1-24. Adrenal
      insufficiency (AI) was defined as a stimulated cortisol level <550 nmol/l.
      RESULTS: There were twenty patients (27.4%) who showed an insufficient rise in
      serum cortisol using traditional HDT criteria and were diagnosed to suffer from
      AI. There were ten individuals who showed insufficient cortisol values after 30
      minutes, rising to sufficient levels at 60 minutes. All patients revealing an
      insufficient cortisol response result after 60 minutes also had an insufficient
      result after 30 minutes. The cortisol value taken after 30 minutes did not add
      incremental diagnostic value in any of the cases under investigation compared
      with the 60 minutes' sample. CONCLUSIONS: Based on the findings of the present
      analysis the utility of a cortisol measurement 30 minutes after high dose ACTH
      injection was low and did not add incremental diagnostic value to a single
      measurement after 60 minutes.

PMID- 25068463
TI  - H2O2-induced decomposition of layer-by-layer films consisting of phenylboronic
      acid-bearing poly(allylamine) and poly(vinyl alcohol).
AB  - Layer-by-layer (LbL) films were prepared by an alternate deposition of
      phenylboronic acid-bearing poly(allylamine hydrochloride) (PBA-PAH) and
      poly(vinyl alcohol) (PVA) on the surface of a quartz slide to develop thin films
      that can be decomposed in response to hydrogen peroxide (H2O2). The PBA-PAH/PVA
      films decomposed in the presence of H2O2; the degree and kinetics of
      decomposition depend on the concentration of H2O2 and on the pH of the solution.
      For example, the film decomposition completely occurred in 30 min in 1.0 mM H2O2
      solution at pH 7.4, while it took 180 min in 0.1 mM H2O2 solution. The H2O2
      induced decomposition of the film can be explained in terms of the oxidative
      scission of the carbon-boron bond in PBA residues in the PBA-PAH chains. A
      potential use of the PBA-PAH/PVA films in developing H2O2-sensitive delivery
      systems was suggested. 

PMID- 25068460
TI  - A novel role of CDX1 in embryonic epicardial development.
AB  - The molecular mechanism that regulates epicardial development has yet to be
      understood. In this study, we explored the function of CDX1, a Caudal-related
      family member, in epicardial epithelial-to-mesenchymal transition (EMT) and in
      the migration and the differentiation of epicardium-derived progenitors into
      vascular smooth muscle cells. We detected a transient expression of CDX1 in
      murine embryonic hearts at 11.5 days post coitum (dpc). Using a doxycycline
      inducible CDX1 mouse model, primary epicardium, and ex vivo heart culture, we
      further demonstrated that ectopic expression of CDX1 promoted epicardial EMT. In
      addition, a low-dose CDX1 induction led to enhanced migration and differentiation
      of epicardium-derived cells into alpha-SMA+ vascular smooth muscles. In contrast,
      either continued high-level induction of CDX1 or CDX1 deficiency attenuated the
      ability of epicardium-derived cells to migrate and to mature into smooth muscles
      induced by TGF-beta1. Further RNA-seq analyses showed that CDX1 induction altered
      the transcript levels of genes involved in neuronal development, angiogenesis,
      and cell adhesions required for EMT. Our data have revealed a previously
      undefined role of CDX1 during epicardial development, and suggest that transient
      expression of CDX1 promotes epicardial EMT, whereas subsequent down-regulation of
      CDX1 after 11.5 dpc in mice is necessary for further subepicardial invasion of
      EPDCs and contribution to coronary vascular endothelium or smooth muscle cells. 

PMID- 25068465
TI  - Study of molecular dynamics in poly(n-alkyl methacrylates) by light induced
      absorption anisotropy.
AB  - Formation of absorbance anisotropy under linearly polarized irradiation at 405 nm
      in films of poly(ethyl methacrylate) (PEMA), poly(n-butyl methacrylate) (PnBMA),
      and poly(n-hexyl methacrylate) (PnHexMA) doped with azo compound has been studied
      in a wide temperature range below Tg. The anisotropy formation kinetics has been
      well described under the assumption that there are two types of environments in
      the polymer matrixes: mobile and immobile. The mobile environment allows the
      dopant to reorient in the course of cis-trans-cis isomerization cycle and the
      immobile environment does not. The fraction of mobile environments was estimated
      to be 0.12 in PEMA, 0.65 in PnBMA, and 1.0 in PnHexMA. An increase in the
      fraction of mobile environments within the series PEMA-PnBMA-PnHexMA have been
      associated with an increase in the size of alkyl nanodomains. The average angle
      of transition dipole rotation upon isomerization and the amplitude of molecules
      librations have been estimated in the temperature range studied. 

PMID- 25068464
TI  - True zero-training brain-computer interfacing--an online study.
AB  - Despite several approaches to realize subject-to-subject transfer of pre-trained
      classifiers, the full performance of a Brain-Computer Interface (BCI) for a novel
      user can only be reached by presenting the BCI system with data from the novel
      user. In typical state-of-the-art BCI systems with a supervised classifier, the
      labeled data is collected during a calibration recording, in which the user is
      asked to perform a specific task. Based on the known labels of this recording,
      the BCI's classifier can learn to decode the individual's brain signals.
      Unfortunately, this calibration recording consumes valuable time. Furthermore, it
      is unproductive with respect to the final BCI application, e.g. text entry.
      Therefore, the calibration period must be reduced to a minimum, which is
      especially important for patients with a limited concentration ability. The main
      contribution of this manuscript is an online study on unsupervised learning in an
      auditory event-related potential (ERP) paradigm. Our results demonstrate that the
      calibration recording can be bypassed by utilizing an unsupervised trained
      classifier, that is initialized randomly and updated during usage. Initially, the
      unsupervised classifier tends to make decoding mistakes, as the classifier might
      not have seen enough data to build a reliable model. Using a constant re-analysis
      of the previously spelled symbols, these initially misspelled symbols can be
      rectified posthoc when the classifier has learned to decode the signals. We
      compare the spelling performance of our unsupervised approach and of the
      unsupervised posthoc approach to the standard supervised calibration-based dogma
      for n = 10 healthy users. To assess the learning behavior of our approach, it is
      unsupervised trained from scratch three times per user. Even with the relatively
      low SNR of an auditory ERP paradigm, the results show that after a limited number
      of trials (30 trials), the unsupervised approach performs comparably to a classic
      supervised model.

PMID- 25068466
TI  - Prospective study on the efficacy of treating normal tension glaucoma with a
      single session of selective laser trabeculoplasty.
AB  - PURPOSE: The purpose of this study was to investigate the efficacy of selective
      laser trabeculoplasty (SLT) in the treatment of normal tension glaucoma (NTG).
      METHODS: This prospective cohort study recruited consecutive cases of NTG on
      antiglaucoma medication. Cases were excluded for previous glaucoma surgery or
      laser. All patients underwent a 1-month washout of medication followed by a mean
      baseline intraocular pressure (IOP) measured at 9 AM, 1 PM, and 5 PM. A 30%
      reduction from baseline was set as the target IOP. A single session of SLT was
      performed to 360 degrees of the trabecular meshwork. IOP phasing was repeated at
      1 month after SLT and medication was resumed to achieve the target IOP. Patients
      were followed up to 6 months after SLT. RESULTS: In 83 eyes of 46 subjects, the
      mean prestudy IOP was 14.2 +/- 3.1 mm Hg when on 1.5 +/- 0.9 antiglaucoma
      medication. The mean baseline IOP without medication was 16.1 +/- 2.2 mm Hg. The
      mean SLT shots applied was 187.8 +/- 27.5 using a mean energy of 1.0 +/- 0.07 mJ.
      At 1-month post-SLT, the IOP was 12.7 +/- 2.0 mm Hg (21.6% IOP reduction) from
      baseline without medication (P<0.05). The 6-month IOP was 11.4 +/- 1.6 mm Hg when
      on 1.1+/- 1.0 medications, representing a 19.7% reduction from prestudy IOP, a
      29.6% reduction from baseline IOP, and a 26.7% reduction in antiglaucoma
      medication (all P< 0.05). A higher baseline IOP was correlated with greater IOP
      reduction with SLT (r=0.3, P=0.009). CONCLUSIONS: A single session of SLT for NTG
      achieved an additional 20% reduction in IOP with 27% less medication at 6 months
      compared with prestudy levels while maintaining a 30% reduction from baseline
      IOP.

PMID- 25068467
TI  - Quadrantwise Comparison of Lens-Iris Distance in Patients With Pseudoexfoliation
      Syndrome and Age-matched Controls.
AB  - PURPOSE: To perform a quadrantwise comparison of the minimum distance between the
      posterior iris and the anterior lens in eyes with pseudoexfoliation syndrome
      (PXS) and age-matched controls. PATIENTS AND METHODS: This study was designed as
      a prospective cross-sectional study. The study population consisted of 60
      patients with PXS and 50 age-matched controls. Anterior segment Scheimpflug
      images of segments 90 to 270, 135 to 315, 180 to 360, and 225 to 45 degrees were
      exported as high-quality JPEG images (1920 pixels wide, 1048 pixels high; each
      pixel having a physical dimension of 8.064*8.064 um) for further evaluation. The
      images were analyzed by Image J software. Minimum lens-iris distance (MLID) of
      the superior, inferior, nasal, and temporal quadrants were analyzed and compared
      between the groups. Anterior chamber depth, anterior chamber angle, pupillary
      diameter, average of K1 and K2 (Km), and cataract grading system by Scheimpflug
      imaging [Oculus Pentacam Nucleus Grading System (PNS)] were also assessed.
      RESULTS: The MLIDs of all quadrants in eyes with PXS were shorter than controls
      and these differences were statistically significant (P<0.05). The shortest
      distance was recorded in the inferior quadrant followed by the superior,
      temporal, and nasal quadrants in both groups. Pupillary diameter was the only
      variable found to be correlated with mean global MLID at a statistically
      significant level (r=-0.465, P<0.001; adjusted for age, sex, anterior chamber
      angle, anterior chamber depth, PNS, and Km). CONCLUSION: Eyes with PXS manifested
      with shorter mean MLID than controls.

PMID- 25068468
TI  - Retrobulbar diversion of aqueous humor: laboratory studies.
AB  - INTRODUCTION: This laboratory-based surgical and histopathologic study evaluates
      the efficacy and explores the mechanism of action of a new form of glaucoma tube
      shunt for glaucoma. Existing polymeric implants frequently become encapsulated
      between the sclera and tenons capsule and become impervious to aqueous humor.
      This pilot study analyzes histologic and tonometric changes after retrobulbar
      diversion of aqueous directly from anterior chamber (AC) into the retrobulbar
      space (RS) versus standard subtenons scleral reservoir diversion. MATERIALS AND
      METHODS: This was an IACUC-approved 6-month masked comparative animal study.
      Front-to-back 1-piece (AC-to-RS) shunts (n=4) and standard Ahmed FP8 shunts (n=3)
      were implanted unilaterally in a total of 7 rabbits. Operative eyes were serially
      monitored throughout the trial period and underwent postmortem histologic
      assessment 24 hours after in vivo intracameral India ink dye injection to discern
      the pathway for retrobulbar aqueous reuptake. RESULTS: Sustained intraocular
      pressure reduction occurred in these normotensive rabbits with AC-RS shunts, from
      preoperative mean 13.5+/-0.3 to mean 10.6+/-0.3 mm Hg through 6 months,
      significantly lower than with the standard FP8 (P<0.001). Qualitative histologic
      analysis revealed lacunar distribution of India ink throughout the RS,
      demonstrating successful diffuse posterior diversion and reuptake of aqueous
      humor. CONCLUSIONS: Retrobulbar shunts can divert aqueous from the AC into the
      RS, potentially overcoming plate encapsulation associated with standard subtenons
      scleral reservoir placement. Elimination of the bleb from the periequatorial
      globe may substantially simplify surgery and obviate the risks of bleb leak.

PMID- 25068469
TI  - Characteristics and Prognostic Analysis of 69 Patients With Pulmonary Sarcomatoid
      Carcinoma.
AB  - BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy. METHODS:
      A total of 69 patients with PSC treated at a single institution in southern China
      with long-term follow-up were evaluated in this study. We analyzed the clinical
      characteristics, immunohistochemical profiles, epidermal growth factor receptor
      mutation status, K-RAS mutation status, treatments, and prognosis. RESULTS: PSC
      mainly occurred in young male patients with a history of smoking. Most patients
      received multimodality treatments and the majority had early-stage disease. The
      median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The
      patients without distant metastasis, with normal or higher body mass index
      (>=18.5), with normal hemoglobin, with smaller tumor size (<=4 cm), and those who
      received complete resection had significantly better overall survival (P<0.05).
      The patients with pleomorphic carcinoma had much worse prognosis. In a Cox
      regression model, M stage, pathology, and having received a complete resection
      were independent prognostic factors (P<0.05). CONCLUSIONS: PSC is a unique lung
      malignancy with poor prognosis. Patients receiving complete resection had better
      prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor
      adjuvant chemotherapy improved patient survival for those with early-stage
      disease. The retrospective design and small sample size limited the
      generalizability. Future multicenter collaborations may be necessary to determine
      the optimal treatment.

PMID- 25068470
TI  - Use of Hematopoietic Growth Factors in Elderly Lung Cancer Patients Receiving
      Chemotherapy: A SEER-Medicare-based Study.
AB  - OBJECTIVES: Hematopoietic growth factors (HGFs) are essential for successful
      completion of chemotherapy in lung cancer patients. However, because of their
      adverse effects, clinical guidelines recommend their use in only selective
      clinical scenarios. This study, for the first time, explores patient
      characteristics and temporal trends associated with HGF utilization among elderly
      lung cancer patients receiving chemotherapy. METHODS: This is a retrospective
      analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare
      linked data containing 80,940 patients, aged 65 years and older, diagnosed with
      stage I to IV lung cancer between 1992 and 2009, and who received chemotherapy.
      Descriptive statistics and logistic regressions were used to examine the
      characteristics associated with 2 types of HGFs-colony stimulating factors (CSFs)
      and erythropoiesis-stimulating agents (ESAs). RESULTS: Twenty-five percent of the
      patients received CSFs and 42% received ESAs. Temporal variations were most
      predictive of HGF utilization, with an increase from 2.6% in 1992 to 47.3% in
      2009 for CSFs and 1.3% to 30.5% for ESAs. Higher chemotherapy-based risk profiles
      increased the odds of HGF receipt 2 to 3 times (P<0.0001). Even after controlling
      for relevant clinical characteristics, unexplained sociodemographic associations
      persisted, suggesting lack of compliance with HGF guidelines. CONCLUSIONS: There
      has been a significant increase in the use of HGFs over time. Although
      chemotherapy-based risk profiles were significant predictors of HGF receipt, the
      study results suggest possible lack of compliance with treatment guidelines,
      which should be investigated. Given the high cost of HGFs, future studies are
      also needed to determine cost-effectiveness of these drugs among lung cancer
      patients.

PMID- 25068471
TI  - Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of
      Bevacizumab in Advanced Pancreas Cancer: A Pooled Analysis of 4 Prospective
      Trials of Gemcitabine-based Therapy With Bevacizumab.
AB  - PURPOSE: Phase III studies of bevacizumab in advanced pancreas cancer (APCA)
      demonstrated no improvement in outcome. No validated biomarkers for bevacizumab
      efficacy exist. We evaluated bevacizumab-related hypertension (B-HTN) as a
      biomarker in APCA patients in a pooled analysis from 4 prospective clinical
      trials of gemcitabine-based therapy combined with bevacizumab. MATERIALS AND
      METHODS: Data were collected from individual databases from 4 prospective, single
      arm phase II trials. Patients were grouped according to B-HTN or no hypertension
      (HTN), and patients with HTN were further grouped according to highest Common
      Terminology Criteria for Adverse Events grade of HTN: grade 1-2 or grade 3-4.
      Clinical outcomes of overall survival, time to progression, overall response rate
      (ORR), and disease control rate (ORR+SD>16 wk) were compared. RESULTS: A total of
      163 patients with stage IV APCA and Eastern Cooperative Oncology Group 0-1 were
      included. Median age was 59 years (range, 33 to 85 y). Thirty-four patients had B
      HTN, and 129 patients had no HTN. Prognostic factors were balanced between
      groups. Patients with any grade B-HTN had a significantly improved median overall
      survival (13.1 vs. 8.1 mo, P=0.0006), median time to tumor progression (7.6 vs.
      5.5 mo, P=0.0074), ORR (47% vs. 16%, P=0.0001), and disease control rate (85% vs.
      59%, P=0.004). There were no differences in outcomes according to HTN grade (1-2
      [N=16] vs. 3-4 [N=18]). CONCLUSIONS: APCA patients who develop any grade of B-HTN
      appear to derive benefit from bevacizumab. Additional investigation is needed to
      identify subgroups of patients who develop B-HTN and are more likely to benefit
      from bevacizumab.

PMID- 25068472
TI  - Transperineal Template-guided Mapping Biopsy Identifies Pathologic Differences
      Between Very-Low-risk and Low-risk Prostate Cancer: Implications for Active
      Surveillance.
AB  - OBJECTIVES: Active surveillance (AS) is increasingly utilized for low-grade
      prostate cancer with the greatest risk being the possibility of missing a high
      grade cancer. We evaluate the role of transperineal template-guided mapping
      biopsy (TTMB) to select patients for AS. METHODS: A total of 131 consecutive,
      prospectively evaluated men with transrectal ultrasound-guided needle biopsy
      (TRUS)-diagnosed very low risk (Gleason score <=6, <=2 positive biopsies,
      prostate-specific antigen [PSA] density <0.15, and <=50% involvement on any core)
      and low risk (Gleason score <=6, clinical stage T1c, and PSA <=10 ng/mL)
      underwent TTMB as a staging procedure. Biopsies were obtained corresponding to 24
      regional biopsy locations. For each patient, the location of each positive biopsy
      core, the number of positive cores, and the percentage involvement of each core
      were reported. RESULTS: After TTMB, TRUS-detected very-low-risk prostate cancer
      patients were less likely to be diagnosed with higher Gleason score, were less
      likely to have bilateral involvement, and had statistically fewer number of
      positive biopsy cores on TTMB. After TTMB, no cancer, very-low-risk, or low-risk
      prostate cancer was detected in 60 of 72 (83.3%) and 19 of 59 (32.2%) of patients
      with very low and low risk, respectively. In multivariate analysis, older age and
      low risk predicted for higher Gleason score at the time of TTMB. CONCLUSIONS:
      Very-low-risk prostate cancer patients have a significantly lower incidence of
      Gleason score upgrading than those with low-risk disease. After TTMB, 83.3% of
      patients with very-low-risk and 32.2% of patients with low-risk disease appear to
      be outstanding candidates for AS.

PMID- 25068473
TI  - Effects of dynamic operating conditions on nitrification in biological rapid sand
      filters for drinking water treatment.
AB  - Biological rapid sand filters are often used to remove ammonium from groundwater
      for drinking water supply. They often operate under dynamic substrate and
      hydraulic loading conditions, which can lead to increased levels of ammonium and
      nitrite in the effluent. To determine the maximum nitrification rates and safe
      operating windows of rapid sand filters, a pilot scale rapid sand filter was used
      to test short-term increased ammonium loads, set by varying either influent
      ammonium concentrations or hydraulic loading rates. Ammonium and iron (flock)
      removal were consistent between the pilot and the full-scale filter.
      Nitrification rates and ammonia-oxidizing bacteria and archaea were quantified
      throughout the depth of the filter. The ammonium removal capacity of the filter
      was determined to be 3.4 g NH4-N m(-3) h(-1), which was 5 times greater than the
      average ammonium loading rate under reference operating conditions. The ammonium
      removal rate of the filter was determined by the ammonium loading rate, but was
      independent of both the flow and influent ammonium concentration individually.
      Ammonia-oxidizing bacteria and archaea were almost equally abundant in the
      filter. Both ammonium removal and ammonia-oxidizing bacteria density were
      strongly stratified, with the highest removal and ammonia-oxidizing bacteria
      densities at the top of the filter. Cell specific ammonium oxidation rates were
      on average 0.6 * 10(2) +/- 0.2 * 10(2) fg NH4-N h(-1) cell(-1). Our findings
      indicate that these rapid sand filters can safely remove both nitrite and
      ammonium over a larger range of loading rates than previously assumed. 

PMID- 25068474
TI  - Carbon nanoparticles trapped in vivo-similar to carbon nanotubes in time
      dependent biodistribution.
AB  - Carbon nanoparticles are in all of the carbon nanomaterials that are presently
      widely pursued for potential bioapplications, but their in vivo biodistribution
      related properties are largely unknown. In this work, highly (13)C-enriched
      carbon nanoparticles were prepared to allow their quantification in biological
      samples by using isotope-ratio mass spectroscopy. The in vivo biodistribution
      results are presented and discussed, and also compared with those of the aqueous
      suspended carbon nanotubes reported previously. The distribution profile and time
      dependencies are largely similar between the nanoparticles and nanotubes, with
      results on both suggesting meaningful accumulation in some major organs over an
      extended period of time. Therefore, the surface modification of carbon
      nanoparticles, preferably the chemical functionalization of the nanoparticles
      with biocompatible molecules or species, is desirable or necessary in the pursuit
      of these nanomaterials for various bioapplications. 

PMID- 25068475
TI  - Palliative care referral among patients hospitalized with advanced heart failure.
AB  - BACKGROUND: Many heart failure (HF) patients experience high symptom burden, but
      palliative care (PC) services have been used infrequently in this population.
      OBJECTIVE: The specific aim of this study was to identify individual-level
      factors associated with PC referral. METHODS: The study sample included adult
      patients hospitalized at an academic medical center with a primary diagnosis of
      HF between January 2005 and June 2010. Inpatient records were merged with the PC
      database to identify HF patients who received PC consultations. The analytical
      sample included 2647 HF admissions. We used descriptive statistics to
      characterize HF patients who received and did not receive PC services. Logistic
      regression analyses were used to identify patient characteristics that predict PC
      referral. RESULTS: Just over 6% of patients with HF were referred to PC during
      their hospitalization. We identified the following statistically significant
      determinants of PC referral: secondary diagnosis of Alzheimer's disease, receipt
      of thoracentesis, intensive care unit (ICU) stay, and prior HF-related
      hospitalizations. CONCLUSIONS: Currently, only a fraction of HF patients who are
      at high risk for morbidity and mortality receive PC services. Additional research
      is needed to identify factors associated with PC referral that can be
      prospectively identified, and to develop better prediction models to identify HF
      patients who may benefit from PC referral.

PMID- 25068477
TI  - pH-responsive PDMS-b-PDMAEMA micelles for intracellular anticancer drug delivery.
AB  - A series of poly(dimethysiloxane)-b-poly(2-(dimethylamino)ethyl methacrylate)
      (PDMS-b-PDMAEMA) block copolymers were synthesized with atom transfer radical
      polymerization (ATRP). In aqueous solution the polymers self-assembled into
      micelles with diameters between 80 and 300 nm, with the ability to encapsulate
      DOX. The polymer with the shortest PDMAEMA block (5 units) displayed excellent
      cell viability, while micelles containing longer PDMAEMA block lengths (13 and 22
      units) led to increased cytotoxicity. The carriers released DOX in response to a
      decrease in pH from 7.4 to 5.5. Confocal laser scanning microscopy (CLSM)
      revealed that nanoparticles were taken up by endocytosis into acidic cell
      compartments. Furthermore, DOX-loaded nanocarriers exhibited intracellular pH
      response as changes in cell morphology and drug release were observed within 24
      h. 

PMID- 25068478
TI  - The new internal medicine fellowship match timeline: a change in the right
      direction.

PMID- 25068479
TI  - Multidimensional human dynamics in mobile phone communications.
AB  - In today's technology-assisted society, social interactions may be expressed
      through a variety of techno-communication channels, including online social
      networks, email and mobile phones (calls, text messages). Consequently, a clear
      grasp of human behavior through the diverse communication media is considered a
      key factor in understanding the formation of the today's information society. So
      far, all previous research on user communication behavior has focused on a sole
      communication activity. In this paper we move forward another step on this
      research path by performing a multidimensional study of human sociality as an
      expression of the use of mobile phones. The paper focuses on user temporal
      communication behavior in the interplay between the two complementary
      communication media, text messages and phone calls, that represent the bi
      dimensional scenario of analysis. Our study provides a theoretical framework for
      analyzing multidimensional bursts as the most general burst category, that
      includes one-dimensional bursts as the simplest case, and offers empirical
      evidence of their nature by following the combined phone call/text message
      communication patterns of approximately one million people over three-month
      period. This quantitative approach enables the design of a generative model
      rooted in the three most significant features of the multidimensional burst - the
      number of dimensions, prevalence and interleaving degree - able to reproduce the
      main media usage attitude. The other findings of the paper include a novel
      multidimensional burst detection algorithm and an insight analysis of the human
      media selection process. 

PMID- 25068480
TI  - Combined application of NMR- and GC-MS-based metabonomics yields a superior
      urinary biomarker panel for bipolar disorder.
AB  - Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed
      by objective laboratory-based modalities. Our previous studies have independently
      used nuclear magnetic resonance (NMR)-based and gas chromatography-mass
      spectrometry (GC-MS)-based metabonomic methods to characterize the urinary
      metabolic profiles of BD subjects and healthy controls (HC). However, the
      combined application of NMR spectroscopy and GC-MS may identify a more
      comprehensive metabolite panel than any single metabonomic platform alone.
      Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that
      generated a panel of five metabolite biomarkers for BD-four GC-MS-derived
      metabolites and one NMR-derived metabolite. This composite biomarker panel could
      effectively discriminate BD subjects from HC, achieving an area under receiver
      operating characteristic curve (AUC) values of 0.974 in a training set and 0.964
      in a test set. Moreover, the diagnostic performance of this panel was
      significantly superior to the previous single platform-derived metabolite panels.
      Thus, the urinary biomarker panel identified here shows promise as an effective
      diagnostic tool for BD. These findings also demonstrate the complementary nature
      of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the
      combination of NMR spectroscopy and GC-MS can identify a more comprehensive
      metabolite panel than applying each platform in isolation. 

PMID- 25068481
TI  - The relative benefits of green versus lean office space: three field experiments.
AB  - Principles of lean office management increasingly call for space to be stripped
      of extraneous decorations so that it can flexibly accommodate changing numbers of
      people and different office functions within the same area. Yet this practice is
      at odds with evidence that office workers' quality of life can be enriched by
      office landscaping that involves the use of plants that have no formal work
      related function. To examine the impact of these competing approaches, 3 field
      experiments were conducted in large commercial offices in The Netherlands and the
      U.K. These examined the impact of lean and "green" offices on subjective
      perceptions of air quality, concentration, and workplace satisfaction as well as
      objective measures of productivity. Two studies were longitudinal, examining
      effects of interventions over subsequent weeks and months. In all 3 experiments
      enhanced outcomes were observed when offices were enriched by plants.
      Implications for theory and practice are discussed.

PMID- 25068482
TI  - The influence of causal connections between symptoms on the diagnosis of mental
      disorders: evidence from online and offline measures.
AB  - An experiment conducted with students and experienced clinicians demonstrated
      very fast and online causal reasoning in the diagnosis of Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders.
      The experiment also demonstrated that clinicians' causal reasoning is triggered
      by information that is directly related to the causal structure that explains the
      symptoms, such as their temporal sequence. The use of causal theories was
      measured through explicit, verbal diagnostic judgments and through the online
      registration of participants' reading times of clinical reports. To detect both
      online and offline causal reasoning, the consistency of clinical reports was
      manipulated. This manipulation was made by varying the temporal order in which
      different symptoms developed in hypothetical clients, and by providing explicit
      information about causal connections between symptoms. The temporal order of
      symptoms affected the clinicians' but not the students' reading times. However,
      offline diagnostic judgments in both groups were influenced by the consistency
      manipulation. Overall, our results suggest that clinicians engage in fast and
      online causal reasoning processes when dealing with diagnostic information
      concerning mental disorders, and that both clinicians and students engage in
      causal reasoning in diagnostic judgment tasks.

PMID- 25068483
TI  - Temperature dependence of solid-state electron exchanges of mixed-valent
      ferrocenated Au monolayer-protected clusters.
AB  - Electron transfers (ETs) in mixed-valent ferrocene/ferrocenium materials are
      ordinarily facile. In contrast, the presence of ~1:1 mixed-valent ferrocenated
      thiolates in the organothiolate ligand shells of <2 nm diameter Au225, Au144, and
      Au25 monolayer-protected clusters (MPCs) exerts a retarding effect on ET between
      them at and below room temperature. Near room temperature, in dry samples,
      bimolecular rate constants for ET between organothiolate-ligated MPCs are
      diminished by the addition of ferrocenated ligands to their ligand shells. At
      lower temperatures (down to ~77 K), the thermally activated (Arrhenius) ET
      process dissipates, and the ET rates become temperature-independent. Among the
      Au225, Au144, and Au25 MPCs, the temperature-independent ET rates fall in the
      same order as at ambient temperatures: Au225 > Au144 > Au25. The MPC ET
      activation energy barriers are little changed by the presence of ferrocenated
      ligands and are primarily determined by the Au nanoparticle core size.

PMID- 25068484
TI  - Migrant youth's emerging dietary patterns in Haiti: the role of peer social
      engagement.
AB  - OBJECTIVE: The present study examines whether rural-to-urban migrant youth
      consume a greater diversity of high-sugar beverages and fried snacks (HSBFS)
      compared with their peers who remain in rural areas. It also tests whether the
      association between migration and HSBFS diversity is moderated by migrant youth's
      social engagement with their peers. DESIGN: Participants were recruited in August
      and September 2011 following the completion of primary school (6th grade) and
      shortly before many rural youth migrate to urban areas. Participants were re
      interviewed six months later. HSBFS diversity was assessed at follow-up; analyses
      control for baseline and follow-up characteristics. SETTING: Baseline interviews
      occurred in rural Southeast Haiti. Follow-up interviews of migrants occurred at
      urban destinations in Haiti. SUBJECTS: The sample includes 215 youth (mean age
      15.9 years; 43.3 % female; 21.9 % rural-to-urban migrants) who were interviewed
      at baseline and follow-up. RESULTS: Rural-to-urban migrant youth consumed a
      greater diversity of HSBFS products at follow-up than their rural counterparts
      (b=0.70, P<=0.05). Moreover, we found that this relationship varied by level of
      peer social engagement. Youth who migrated and had a high degree of peer social
      engagement consumed 2.2 additional types of HSBFS products daily than their
      counterparts who remained in rural areas and had low peer social engagement.
      CONCLUSIONS: Higher HSBFS diversity among migrant youth is consistent with the
      patterns proposed by the nutrition transition. Interactions with peers may have
      an important influence as migrant youth adopt new dietary preferences. Emerging
      dietary patterns among youth migrants have important implications for health
      trajectories and the development of degenerative diseases.

PMID- 25068486
TI  - Light management in flexible glass by wood cellulose coating.
AB  - Ultra-thin flexible glass with high transparency is attractive for a broad range
      of display applications; however, substrates with low optical haze are not ideal
      for thin film solar cells, since most of the light will go through the
      semiconductor layer without scattering, and the length of light travelling path
      in the active layer is small. By simply depositing a layer of TEMPO (2,2,6,6
      tetramethylpiperidine-1-oxyl radical)-oxidized wood fibers (TOWFs), we are able
      to tailor the optical properties of flexible glass dramatically from exhibiting
      low haze (<1%) to high haze (~56%) without compromising the total forward
      transmittance (~90%). The influence of the TOWFs morphology on the optical
      properties of TOWFs-coated flexible glass is investigated. As the average fiber
      length decreases, the transmission haze of TOWF-coated flexible glass illustrates
      a decreasing trend. Earth-abundant natural materials for transparent, hazy, and
      flexible glass have tremendous applicability in the fabrication of flexible
      optoelectronics with tunable light scattering effects by enabling inexpensive and
      large-scale processes. 

PMID- 25068485
TI  - Oxetanyl peptides: novel peptidomimetic modules for medicinal chemistry.
AB  - The synthesis of novel oxetanyl peptides, where the amide bond is replaced by a
      non-hydrolyzable oxetanylamine fragment, is reported. This new class of pseudo
      dipeptides with the same H-bond donor/acceptor pattern found in proteins expands
      the repertoire of peptidomimetics. 

PMID- 25068487
TI  - Contingency learning deficits and generalization in chronic unilateral hand pain
      patients.
AB  - Contingency learning, in particular the formation of danger beliefs, underpins
      conditioned fear and avoidance behavior, yet equally important is the formation
      of safety beliefs. That is, when threat beliefs and accompanying fear/avoidance
      spread to technically safe cues, it might cause disability. Indeed, such over
      generalization has been advanced as a trans-diagnostic pathologic marker, but it
      has not been investigated in chronic pain. Using a novel hand pain scenario
      contingency learning task, we tested the hypotheses that chronic hand pain
      patients demonstrate less differential pain expectancy judgments because of poor
      safety learning and demonstrate broader generalization gradients than healthy
      controls. Participants viewed digitized 3-dimensional hands in different postures
      presented in random order (conditioned stimulus [CS]) and rated the likelihood
      that a fictive patient would feel pain when moving the hand into that posture.
      Subsequently, the outcome (pain/no pain) was presented on the screen. One hand
      posture was followed by pain (CS+), another was not (CS-). Generalization was
      tested using novel hand postures (generalization stimuli) that varied in how
      similar they were to the original conditioned stimuli. Patients, but not healthy
      controls, demonstrated a contingency learning deficit determined by impaired
      safety learning, but not by exaggerated pain expectancy toward the CS+. Patients
      showed flatter, asymmetric generalization gradients than the healthy controls
      did, with higher pain expectancy for novel postures that were more similar to the
      original CS-. The results clearly uphold our hypotheses and suggest that
      contingency learning deficits might be important in the development and
      maintenance of the chronic pain-related disability. PERSPECTIVE: Chronic hand
      pain patients demonstrate 1) reduced differential contingency learning determined
      by a lack of safety belief formation, but not by exaggerated threat belief
      formation, and 2) flatter, asymmetric generalization gradients than the healthy
      controls.

PMID- 25068488
TI  - Cytoplasmic polyadenylation element binding proteins in development, health, and
      disease.
AB  - The cytoplasmic polyadenylation element binding (CPEB) proteins are sequence
      specific mRNA binding proteins that control translation in development, health,
      and disease. CPEB1, the founding member of this family, has become an important
      model for illustrating general principles of translational control by cytoplasmic
      polyadenylation in gametogenesis, cancer etiology, synaptic plasticity, learning,
      and memory. Although the biological functions of the other members of this
      protein family in vertebrates are just beginning to emerge, it is already evident
      that they, too, mediate important processes, such as cancer etiology and higher
      cognitive function. In Drosophila, the CPEB proteins Orb and Orb2 play key roles
      in oogenesis and in neuronal function, as do related proteins in Caenorhabditis
      elegans and Aplysia. We review the biochemical features of the CPEB proteins,
      discuss their activities in several biological systems, and illustrate how
      understanding CPEB activity in model organisms has an important impact on
      neurological disease. 

PMID- 25068489
TI  - Efficient transfer entropy analysis of non-stationary neural time series.
AB  - Information theory allows us to investigate information processing in neural
      systems in terms of information transfer, storage and modification. Especially
      the measure of information transfer, transfer entropy, has seen a dramatic surge
      of interest in neuroscience. Estimating transfer entropy from two processes
      requires the observation of multiple realizations of these processes to estimate
      associated probability density functions. To obtain these necessary observations,
      available estimators typically assume stationarity of processes to allow pooling
      of observations over time. This assumption however, is a major obstacle to the
      application of these estimators in neuroscience as observed processes are often
      non-stationary. As a solution, Gomez-Herrero and colleagues theoretically showed
      that the stationarity assumption may be avoided by estimating transfer entropy
      from an ensemble of realizations. Such an ensemble of realizations is often
      readily available in neuroscience experiments in the form of experimental trials.
      Thus, in this work we combine the ensemble method with a recently proposed
      transfer entropy estimator to make transfer entropy estimation applicable to non
      stationary time series. We present an efficient implementation of the approach
      that is suitable for the increased computational demand of the ensemble method's
      practical application. In particular, we use a massively parallel implementation
      for a graphics processing unit to handle the computationally most heavy aspects
      of the ensemble method for transfer entropy estimation. We test the performance
      and robustness of our implementation on data from numerical simulations of
      stochastic processes. We also demonstrate the applicability of the ensemble
      method to magnetoencephalographic data. While we mainly evaluate the proposed
      method for neuroscience data, we expect it to be applicable in a variety of
      fields that are concerned with the analysis of information transfer in complex
      biological, social, and artificial systems. 

PMID- 25068491
TI  - Correlation of blood Cr(III) and adverse health effects: Application of PBPK
      modeling to determine non-toxic blood concentrations.
AB  - Chromium (Cr) (III) is a trace metal essential to human health and exposure
      typically occurs via the diet on a daily basis. Some groups of individuals, such
      as those consuming Cr(III) supplements or patients with Cr-containing implants,
      may have elevated blood Cr(III) concentrations. Although blood Cr(III) levels are
      thought to be an accurate metric of exposure, little is known about the
      relationship between these concentrations and possible adverse health risks. This
      study evaluated the various effects reported in animal and human epidemiological
      studies of Cr(III) exposure in an attempt to correlate them with blood Cr(III)
      concentrations. The target endpoints identified in this analysis included the
      hematological, hepatic, and renal systems. Animal and human physiological-based
      pharmacokinetic (PBPK) models were used to estimate steady state blood Cr(III)
      concentrations from a variety of dosing regimens. Based on the animal studies,
      our results suggest that blood Cr(III) concentrations as high as 480-580 MUg/L
      are not associated with any responses. For each of the three health endpoints
      considered in this analysis (hematological, hepatic, and renal) no adverse
      effects were observed below 3,700 MUg/L. Some hematological responses were
      observed at 3,700 MUg/L, and adverse effects clearly occurred at 7,500 MUg/L.
      These findings can be used to assess potential health risks to individuals with
      elevated blood Cr(III) concentrations.

PMID- 25068492
TI  - Re: Pierce et al. Diacetyl and 2,3-pentanedione exposures associated with
      cigarette smoking: implications for risk assessment of food and flavoring workers
      Crit Rev Toxicol, 2014; 44(5):420-435.

PMID- 25068490
TI  - Improving the risk assessment of lipophilic persistent environmental chemicals in
      breast milk.
AB  - Lipophilic persistent environmental chemicals (LPECs) have the potential to
      accumulate within a woman's body lipids over the course of many years prior to
      pregnancy, to partition into human milk, and to transfer to infants upon
      breastfeeding. As a result of this accumulation and partitioning, a breastfeeding
      infant's intake of these LPECs may be much greater than his/her mother's average
      daily exposure. Because the developmental period sets the stage for lifelong
      health, it is important to be able to accurately assess chemical exposures in
      early life. In many cases, current human health risk assessment methods do not
      account for differences between maternal and infant exposures to LPECs or for
      lifestage-specific effects of exposure to these chemicals. Because of their
      persistence and accumulation in body lipids and partitioning into breast milk,
      LPECs present unique challenges for each component of the human health risk
      assessment process, including hazard identification, dose-response assessment,
      and exposure assessment. Specific biological modeling approaches are available to
      support both dose-response and exposure assessment for lactational exposures to
      LPECs. Yet, lack of data limits the application of these approaches. The goal of
      this review is to outline the available approaches and to identify key issues
      that, if addressed, could improve efforts to apply these approaches to risk
      assessment of lactational exposure to these chemicals.

PMID- 25068493
TI  - Response to Muge Akpinar-Elci Letter to Editor re. Pierce et al., Diacetyl and
      2,3-pentanedione exposures associated with cigarette smoking: implications for
      risk assessment of food and flavoring workers, Crit. Rev. Toxicol. 44(5):420-435,
      2014.

PMID- 25068495
TI  - Denervation of the metacarpophalangeal joint.
AB  - Metacarpophalangeal joint osteoarthritis is a relatively common condition that
      hand surgeons have to deal with. When daily activities are impaired by pain and
      all conservative measures have failed, surgical treatments such as arthrodesis or
      joint replacement are indicated. In this article, a technique for joint
      denervation is presented as a treatment for painful degenerative or posttraumatic
      osteoarthritis. Its preliminary results, potential complications, and
      contraindications are also discussed. 

PMID- 25068494
TI  - Claudin 2 deficiency reduces bile flow and increases susceptibility to
      cholesterol gallstone disease in mice.
AB  - BACKGROUND & AIMS: Bile formation and secretion are essential functions of the
      hepatobiliary system. Bile flow is generated by transepithelial transport of
      water and ionic/nonionic solutes via transcellular and paracellular pathways that
      is mainly driven by osmotic pressure. We examined the role of tight junction
      based paracellular transport in bile secretion. Claudins are cell-cell adhesion
      molecules in tight junctions that create the paracellular barrier. The claudin
      family has 27 reported members, some of which have paracellular ion- and/or water
      channel-like functions. Claudin 2 is a paracellular channel-forming protein that
      is highly expressed in hepatocytes and cholangiocytes; we examined the
      hepatobiliary system of claudin 2 knockout (Cldn2(-/-)) mice. METHODS: We
      collected liver and biliary tissues from Cldn2(-/-) and Cldn2(+/+) mice and
      performed histologic, biochemical, and electrophysiologic analyses. We measured
      osmotic movement of water and/or ions in Cldn2(-/-) and Cldn2(+/+) hepatocytes
      and bile ducts. Mice were placed on lithogenic diets for 4 weeks and development
      of gallstone disease was assessed. RESULTS: The rate of bile flow in Cldn2(-/-)
      mice was half that of Cldn2(+/+) mice, resulting in significantly more
      concentrated bile in livers of Cldn2(-/-) mice. Consistent with these findings,
      osmotic gradient-driven water flow was significantly reduced in hepatocyte bile
      canaliculi and bile ducts isolated from Cldn2(-/-) mice, compared with Cldn2(+/+)
      mice. After 4 weeks on lithogenic diets, all Cldn2(-/-) mice developed
      macroscopically visible gallstones; the main component of the gallstones was
      cholesterol (>98%). In contrast, none of the Cldn2(+/+) mice placed on lithogenic
      diets developed gallstones. CONCLUSIONS: Based on studies of Cldn2(-/-) mice,
      claudin 2 regulates paracellular ion and water flow required for proper
      regulation of bile composition and flow. Dysregulation of this process increases
      susceptibility to cholesterol gallstone disease in mice.

PMID- 25068496
TI  - Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading,
      vaccination, and protection using intranasally administered antigen-pulsed
      dendritic cells.
AB  - Dendritic cells (DCs) play a critical role in the generation of adaptive immunity
      via the efficient capture, processing, and presentation of antigen (Ag) to naive
      T cells. Administration of Ag-pulsed DCs is also an effective strategy for
      enhancing immunity to tumors and infectious disease organisms. Studies have also
      demonstrated that targeting Ags to Fcgamma receptors (FcgammaR) on Ag presenting
      cells can enhance humoral and cellular immunity in vitro and in vivo.
      Specifically, our studies using a Francisella tularensis (Ft) infectious disease
      vaccine model have demonstrated that targeting immunogens to FcgammaR via
      intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft
      (iFt) immune complexes (ICs) enhances protection against Ft challenge. Ft is the
      causative agent of tularemia, a debilitating disease of humans and other mammals
      and a category A biothreat agent for which there is no approved vaccine.
      Therefore, using iFt Ag as a model immunogen, we sought to determine if ex vivo
      targeting of iFt to FcgammaR on DCs would enhance the potency of i.n.
      administered iFt-pulsed DCs. In this study, bone marrow-derived DCs (BMDCs) were
      pulsed ex vivo with iFt or mAb-iFt ICs. Intranasal administration of mAb-iFt
      pulsed BMDCs enhanced humoral and cellular immune responses, as well as
      protection against Ft live vaccine strain (LVS) challenge. Increased protection
      correlated with increased iFt loading on the BMDC surface as a consequence of
      FcgammaR-targeting. However, the inhibitory FcgammaRIIB had no impact on this
      enhancement. In conclusion, targeting Ag ex vivo to FcgammaR on DCs provides a
      method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag
      required, while also avoiding the inhibitory impact of FcgammaRIIB. Thus, this
      represents a simple and less invasive strategy for increasing the potency of ex
      vivo-pulsed DC vaccines against chronic infectious diseases and cancer.

PMID- 25068498
TI  - Cubanes in medicinal chemistry: synthesis of functionalized building blocks.
AB  - A collection of novel, pharmaceutically relevant cubane-containing molecules has
      been prepared from the commercially available cubane-1,4-dimethylester. A range
      of synthetic methods have been applied to prepare these cubane building blocks
      with one or two functional handles to allow easy incorporation into existing
      medicinal chemistry programs. 

PMID- 25068497
TI  - Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine
      candidate in healthy children: a randomized phase I clinical trial.
AB  - A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7
      TT contains 2 MUg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 MUg of 6B, each one
      conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes
      that cause most invasive pneumococcal diseases (IPD) worldwide. In the present
      study, we investigated the safety and explored the immunogenicity of PCV7-TT
      during a controlled, randomized and double blind clinical trial phase I in 4-5
      year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as
      control vaccine. Following a single-dose vaccination, all individual serotypes
      included in PCV7-TT induced statistically significant increase of IgG GMC and OPA
      GMT. These are the first clinical results of PCV7-TT in children and they pave
      the way toward next clinical trials in children and infants. This clinical trial
      was published in the Cuban Public Register of Clinical Trials with code
      RPCEC00000173.

PMID- 25068499
TI  - Hybridization of G-quadruplex-forming peptide nucleic acids to guanine-rich DNA
      templates inhibits DNA polymerase eta extension.
AB  - The guanine quadruplex (G-quadruplex) is a highly stable secondary structure that
      forms in G-rich repeats of DNA, which can interfere with DNA processes, including
      DNA replication and transcription. We showed previously that short guanine-rich
      peptide nucleic acids (PNAs) can form highly stable hybrid quadruplexes with DNA.
      We hypothesized that such structures would provide a stronger block to polymerase
      extension on G-rich templates than a native DNA homoquadruplex because of the
      greater thermodynamic stability of the PNA-DNA hybrid structures. To test this,
      we analyzed the DNA primer extension activity of polymerase eta, a translesion
      polymerase implicated in synthesis past G-quadruplex blocks, on DNA templates
      containing guanine repeats. We observed a PNA concentration-dependent decrease in
      the level of polymerase eta extension to the end of the template and an increase
      in the level of polymerase eta inhibition at the sequence prior to the G-rich
      repeats. In contrast, the addition of a complementary C-rich PNA that hybridizes
      to the G-rich repeats by Watson-Crick base pairing led to a decrease in the level
      of polymerase inhibition and an increase in the level of full-length extension
      products. The G-quadruplex-forming PNA exhibited inhibition (IC50=16.2+/-3.3 nM)
      of polymerase eta DNA synthesis on the G-rich templates stronger than that of the
      established G-quadruplex-stabilizing ligand BRACO-19 (IC50=42.5+/-4.8 nM). Our
      results indicate that homologous PNA targeting of G-rich sequences creates stable
      PNA-DNA heteroquadruplexes that inhibit polymerase eta extension more effectively
      than a DNA homoquadruplex. The implications of these results for the potential
      development of homologous PNAs as therapeutics for halting proliferating cancer
      cells are discussed.

PMID- 25068500
TI  - The seleno-organic compound ebselen impairs mitochondrial physiology and induces
      cell death in AR42J cells.
AB  - Ebselen is a seleno-organic compound that causes cell death in several cancer
      cell types. The mechanisms underlying its deleterious effects have not been fully
      elucidated. In this study, the effects of ebselen (1 MUM-40 MUM) on AR42J tumor
      cells have been examined. Cell viability was studied using AlamarBlue((r)) test.
      Cell cycle phase determination was carried out by flow cytometry. Changes in
      intracellular free Ca(2+) concentration were followed by fluorimetry analysis of
      fura-2-loaded cells. Distribution of mitochondria, mitochondrial Ca(2+)
      concentration and mitochondrial membrane potential were monitored by confocal
      microscopy of cells loaded with Mitotracker GreenTM FM, rhod-2 or TMRM
      respectively. Caspase-3 activity was calculated following the luorogenic
      substrate ACDEVD-AMC signal with a spectrofluorimeter. Results show that cell
      viability decreased in the presence of ebselen. An increase in the number of
      cells in the S-phase of the cell cycle was observed. Ebselen induced a
      concentration-dependent mobilization of Ca(2+) from agonist- and thapsigargin
      sensitive Ca(2+) pools. Ebselen induced also a transient increase in
      mitochondrial Ca(2+) concentration, a progressive decrease of the mitochondrial
      membrane potential and a disruption of the mitochondrial network. Finally, a
      concentration-dependent increase in caspase-3 activity was detected. We conclude
      that ebselen exerts deleterious actions on the cells that involve the impairment
      of mitochondrial physiology and the activation of caspase-3-mediated apoptotic
      pathway.

PMID- 25068501
TI  - Unintended consequences of expensive cancer therapeutics-the pursuit of marginal
      indications and a me-too mentality that stifles innovation and creativity: the
      John Conley Lecture.
AB  - Cancer is expected to continue as a major health and economic problem worldwide.
      Several factors are contributing to the increasing economic burden imposed by
      cancer, with the cost of cancer drugs an undeniably important variable. The use
      of expensive therapies with marginal benefits for their approved indications and
      for unproven indications is contributing to the rising cost of cancer care. We
      believe that expensive therapies are stifling progress by (1) encouraging
      enormous expenditures of time, money, and resources on marginal therapeutic
      indications and (2) promoting a me-too mentality that is stifling innovation and
      creativity. The modest gains of Food and Drug Administration-approved therapies
      and the limited progress against major cancers is evidence of a lowering of the
      efficacy bar that, together with high drug prices, has inadvertently incentivized
      the pursuit of marginal outcomes and a me-too mentality evidenced by the
      duplication of effort and redundant pharmaceutical pipelines. We discuss the
      economic realities that are driving this process and provide suggestions for
      radical changes to reengineer our collective cancer ecosystem to achieve better
      outcomes for society. 

PMID- 25068502
TI  - Characterization of a human-pathogenic Acanthamoeba griffini isolated from a
      contact lens-wearing keratitis patient in Spain.
AB  - Amoebae were isolated from contact lenses of a symptomatic lens wearer in Spain.
      Protozoa were characterized by studying their morphology, biology, protease
      activity and the 18S rRNA gene sequence. Morphology of the organism was observed
      by light microscopy, scanning electron microscopy and transmission electron
      microscopy. Its structure corresponded to an amphizoic amoeba. The protozoa grew
      well at 37  degrees C and poorly at lower temperatures. In addition, it was
      capable of lysing mammalian cells in vitro. A major 56 kDa proteolytic enzyme was
      observed in amoeba crude extracts by gelatin-sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. Most proteolytic enzymes in protozoa extracts
      showed significant activity over a wide range of pH (3-9) and temperature (8-45 
      degrees C) values. The assays on inhibition of protease activity indicated
      strongly that enzymes detected in amoeba extracts corresponded to serine
      proteases and, to a lesser extent, cysteine proteases. The use of proteinase
      inhibitors on a tissue culture model proved that the proteinase activity is
      critical for developing focal lesions in HeLa cell monolayers. Finally, partial
      sequencing of the 18S ribosomal RNA gene and phylogenetic analyses indicated that
      the isolate is closely related to Acanthamoeba griffini H37 from the UK (T3
      genotype).

PMID- 25068503
TI  - Zethrenes, extended p-quinodimethanes, and periacenes with a singlet biradical
      ground state.
AB  - Researchers have studied polycyclic aromatic hydrocarbons (PAHs) for more than
      100 years, and most PAHs in the neutral state reported so far have a closed-shell
      electronic configuration in the ground state. However, recent studies have
      revealed that specific types of polycyclic hydrocarbons (PHs) could have a
      singlet biradical ground state and exhibit unique electronic, optical, and
      magnetic activities. With the appropriate stabilization, these new compounds
      could prove useful as molecular materials for organic electronics, nonlinear
      optics, organic spintronics, organic photovoltaics, and energy storage devices.
      However, before researchers can use these materials to design new devices, they
      need better methods to synthesize these molecules and a better understanding of
      the fundamental relationship between the structure and biradical character of
      these compounds and their physical properties. Their biradical character makes
      these compounds difficult to synthesize. These compounds are also challenging to
      physically characterize and require the use of various experimental techniques
      and theoretic methods to comprehensively describe their unique properties. In
      this Account, we will discuss the chemistry and physics of three types of PHs
      with a significant singlet biradical character, primarily developed in our group.
      These structures are zethrenes, Z-shaped quinoidal hydrocarbons; hydrocarbons
      that include a proaromatic extended p-quinodimethane unit; and periacenes, acenes
      fused in a peri-arrangement. We used a variety of synthetic methods to prepare
      these compounds and stabilized them using both thermodynamic and kinetic
      approaches. We probed their ground-state structures by electronic absorption,
      NMR, ESR, SQUID, Raman spectroscopy, and X-ray crystallography and also performed
      density functional theory calculations. We investigated the physical properties
      of these PHs using various experimental methods such as one-photon absorption,
      two-photon absorption, transient absorption spectroscopy, electrochemistry, and
      spectroelectrochemistry. These systematic studies revealed that aromaticity
      played a very important role in determining their singlet biradical character,
      which is critically related to both their physical properties and their chemical
      reactivity. In particular, we found that Clar's aromatic sextet rule, which is
      useful for the closed-shell PAHs, can also predict the relative biradical
      character of benzenoid PH-based singlet biradicaloids. Other factors, such as
      structural flexibility of the biradical and quinoid resonance forms and the
      participation of the substitution in the pi-conjugation, also influence the
      biradical character. These molecular materials demonstrate a number of unique
      properties such as near-infrared absorption, redox amphotericity, large two
      photon absorption cross section, short excited state lifetime, stimuli-responsive
      magnetic activity, and singlet fission, which suggests promise for future
      applications.

PMID- 25068504
TI  - Gradient FeO(x)(PO4)(y) layer on hematite photoanodes: novel structure for
      efficient light-driven water oxidation.
AB  - Hematite has been receiving increasing attention for its application in
      photoelectrochemical (PEC) water oxidation but usually exhibits poor efficiency.
      We fabricated a stable gradient-structured FeOx(PO4)y layer on hematite by
      diffusively incorporating phosphate onto the surface layer of hematite films at a
      low temperature. X-ray photoelectron spectroscopy depth profile and Fe K-edge
      grazing-incidence X-ray absorption near-edge structure and extended X-ray
      absorption fine structure analysis demonstrated the formation of a ~50 nm
      overlayer with a gradient phosphorus distribution and structural evolution from
      the outer surface to the depth. The as-prepared photoanodes showed highly
      improved PEC water oxidation performance. Up to 8.5-fold enhancement in the
      photocurrent density at 1.23 V versus reversible hydrogen electrode was achieved
      relative to the pristine anode. This strategy is applicable for hematite
      photoanodes prepared by different methods and with different morphologies and
      structures. The improvement in the water oxidation activity is mainly attributed
      to the enhanced separation of photogenerated electron-hole pairs, which is
      derived from the increased hole diffusion length in the gradient-structured
      overlayer. This work develops a simple and universal method to boost the PEC
      water oxidation efficiency with versatile hematite photoanodes. 

PMID- 25068505
TI  - Association between genetic polymorphisms in the ADAM33 gene and asthma risk: a
      meta-analysis.
AB  - The aim of this study was to evaluate the associations between the rs3918396 G>A
      and rs528557 C>G polymorphisms in the disinterring and metalloproteinase domain
      33 (ADAM33) gene and asthma risk. We searched CISCOM, CINAHL, Web of Science,
      PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception
      through August 1st, 2013 without language restrictions. Meta-analysis was
      performed using the STATA 12.0 software. Crude odds ratios (ORs) with their 95%
      confidence intervals (95% CI) were calculated. Thirteen case-control studies were
      included with a total of 7104 asthma patients and 8172 healthy controls. Our meta
      analysis results revealed that ADAM33 rs528557 C>G polymorphism was associated
      with an increased risk of asthma (all p<0.05). However, we found no correlation
      between the ADAM33 rs3918396 G>A polymorphism and asthma risk (all p>0.05).
      Subgroup analysis by ethnicity indicated that the ADAM33 rs528557 C>G
      polymorphism might be strongly associated with an increased risk of asthma among
      both Caucasian and Asian populations (All p<0.05). No significant association was
      found between the ADAM33 rs3918396 G>A polymorphism and the risk of asthma among
      the studied ethnicities (All p>0.05). The present meta-analysis suggests that the
      ADAM33 rs528557 C>G polymorphism may contribute to susceptibility to asthma.
      Thus, the ADAM33 rs528557 C>G polymorphism may be utilized as a biomarker for
      early diagnosis of asthma. 

PMID- 25068506
TI  - Systems pharmacology modeling predicts delayed presentation and species
      differences in bile acid-mediated troglitazone hepatotoxicity.
AB  - Troglitazone (TGZ) causes delayed, life-threatening drug-induced liver injury in
      some patients but was not hepatotoxic in rats. This study investigated altered
      bile acid homeostasis as a mechanism of TGZ hepatotoxicity using a systems
      pharmacology model incorporating drug/metabolite disposition, bile acid
      physiology/pathophysiology, hepatocyte life cycle, and liver injury biomarkers.
      In the simulated human population, TGZ (200-600 mg/day * 6 months) resulted in
      delayed increases in serum alanine transaminase >3* the upper limit of normal in
      0.3-5.1%, with concomitant bilirubin elevations >2* the upper limit of normal in
      0.3-3.6%, of the population. By contrast, pioglitazone (15-45 mg/day * 6 months)
      did not elicit hepatotoxicity, consistent with clinical data. TGZ was not
      hepatotoxic in the simulated rat population. In summary, mechanistic modeling
      based only on bile acid effects accurately predicted the incidence, delayed
      presentation, and species differences in TGZ hepatotoxicity, in addition to
      predicting the relative liver safety of pioglitazone. Systems pharmacology models
      integrating physiology and experimental data can evaluate drug-induced liver
      injury mechanisms and may be useful to predict the hepatotoxic potential of drug
      candidates. 

PMID- 25068507
TI  - High resolution melting analysis: a rapid and accurate method to detect CALR
      mutations.
AB  - BACKGROUND: The recent discovery of CALR mutations in essential thrombocythemia
      (ET) and primary myelofibrosis (PMF) patients without JAK2/MPL mutations has
      emerged as a relevant finding for the molecular diagnosis of these
      myeloproliferative neoplasms (MPN). We tested the feasibility of high-resolution
      melting (HRM) as a screening method for rapid detection of CALR mutations.
      METHODS: CALR was studied in wild-type JAK2/MPL patients including 34 ET, 21
      persistent thrombocytosis suggestive of MPN and 98 suspected secondary
      thrombocytosis. CALR mutation analysis was performed through HRM and Sanger
      sequencing. We compared clinical features of CALR-mutated versus 45 JAK2/MPL
      mutated subjects in ET. RESULTS: Nineteen samples showed distinct HRM patterns
      from wild-type. Of them, 18 were mutations and one a polymorphism as confirmed by
      direct sequencing. CALR mutations were present in 44% of ET (15/34), 14% of
      persistent thrombocytosis suggestive of MPN (3/21) and none of the secondary
      thrombocytosis (0/98). Of the 18 mutants, 9 were 52 bp deletions, 8 were 5 bp
      insertions and other was a complex mutation with insertion/deletion. No mutations
      were found after sequencing analysis of 45 samples displaying wild-type HRM
      curves. HRM technique was reproducible, no false positive or negative were
      detected and the limit of detection was of 3%. CONCLUSIONS: This study
      establishes a sensitive, reliable and rapid HRM method to screen for the presence
      of CALR mutations.

PMID- 25068508
TI  - 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in
      nude mice.
AB  - BACKGROUND: CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin
      lymphoma (NHL) and chronic lymphocytic leukemia cells (CLL). The anti-CD37
      monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA
      and labelled with the beta-particle emitting radionuclide 177Lu creating the
      radio-immunoconjugate (RIC) 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin). The
      present toxicity study was performed prior to initiation of clinical studies with
      177Lu-HH1. METHODOLOGY/PRINCIPAL FINDINGS: Nude mice with or without tumor
      xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for
      clinical signs of toxicity up to ten months. Acute, life threatening bone marrow
      toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1.
      Significant changes in serum concentrations of liver enzymes were evident for
      treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and
      atrophy, and interstitial cell hyperplasia of the ovaries were also observed for
      mice in this dose group. CONCLUSIONS/SIGNIFICANCE: 177Lu-DOTA-HH1 was well
      tolerated at dosages about 10 times above those considered relevant for
      radioimmunotherapy in patients with B-cell derived malignancies.The toxicity
      profile was as expected for RICs. Our experimental results have paved the way for
      clinical evaluation of 177Lu-HH1 in NHL patients.

PMID- 25068509
TI  - Understanding the structural parameters of biocompatible nanoparticles dictating
      protein fouling.
AB  - The development of nanocarriers for biomedical applications requires that these
      nanocarriers have special properties, including resistance to nonspecific protein
      adsorption. In this study, the fouling properties of PLA- and PCL-based block
      copolymer nanoparticles (NPs) have been evaluated by placing them in contact with
      model proteins. Block copolymer NPs were produced through the self-assembly of
      PEOm-b-PLAn and PEOm-b-PCLn. This procedure yielded nanosized objects with
      distinct structural features dependent on the length of the hydrophobic and
      hydrophilic blocks and the volume ratio. The protein adsorption events were
      examined in relation to size, chain length, surface curvature, and hydrophilic
      chain density. Fouling by BSA and lysozyme was considerably reduced as the length
      of the hydrophilic PEO-stabilizing shell increases. In contrast to the case of
      hydrophilic polymer-grafted planar surfaces, the current investigations suggest
      that the hydrophilic chain density did not markedly influence protein fouling.
      The protein adsorption took place at the outer surface of the NPs since neither
      BSA nor lysozyme was able to diffuse within the hydrophilic layer due to
      geometric restrictions. Protein binding is an exothermic process, and it is
      modulated mainly by polymer features. The secondary structures of BSA and
      lysozyme were not affected by the adhesion phenomena. 

PMID- 25068513
TI  - Real-time detection of metal ions using conjugated polymer composite papers.
AB  - Cellulose, a natural polymeric material, has widespread technical applications
      because of its inherent structural rigidity and high surface area. As a
      conjugated polymer, polypyrrole shows practical potential for a diverse and
      promising range of future technologies. Here, we demonstrate a strategy for the
      real-time detection and removal of metal ions with polypyrrole/cellulose (PPCL)
      composite papers in solution. Simply, the conjugated polymer papers had different
      chemical/physical properties by applying different potentials to them, which
      resulted in differentiable response patterns and adsorption efficiencies for
      individual metal ions. First, large-area PPCL papers with a diameter of 5 cm were
      readily obtained via vapor deposition polymerization. The papers exhibited both
      mechanical flexibility and robustness, in which polypyrrole retained its redox
      property perfectly. The ability of the PPCL papers to recognize metal ions was
      examined in static and flow cells, in which real-time current change was
      monitored at five different applied potentials (+1, +0.5, 0, -0.5, and -1 V vs.
      Ag/AgCl). Distinguishable signals in the PPCL paper responses were observed for
      individual metal ions through principal component analysis. Particularly, the
      PPCL papers yielded unique signatures for three metal ions, Hg(ii), Ag(i), and
      Cr(iii), even in a real sample, groundwater. The sorption of metal ions by PPCL
      papers was examined in the flow system. The PPCL papers had a greatly superior
      adsorption efficiency for Hg(ii) compared to that of the other metal ions. With
      the strong demand for the development of inexpensive, flexible, light-weight, and
      environmentally friendly devices, the fascinating characteristics of these PPCL
      papers are likely to provide good opportunities for low-cost paper-based flexible
      or wearable devices. 

PMID- 25068510
TI  - Deficient pain modulatory systems in patients with mild traumatic brain and
      chronic post-traumatic headache: implications for its mechanism.
AB  - Although the prevalence rate of chronic post-traumatic headache (CPTHA) after
      mild traumatic brain injury (TBI) reaches up to 95%, its mechanism is unknown,
      and little is known about the characteristics of the pain system in this
      condition. Our aim was to investigate the capabilities of two pain modulatory
      systems among individuals with CPTHA and study their association with CPTHA, here
      for the first time. Forty-six subjects participated; 16 with TBI and CPTHA, 12
      with TBI without CPTHA, and 18 healthy controls. Testing included the measurement
      of heat-pain (HPT) and pressure-pain (PPT) thresholds in the forehead and
      forearm, pain adaptation to tonic noxious heat, and conditioned pain modulation
      (CPM).The participants completed a post-traumatic stress disorder (PTSD)
      questionnaire. The two TBI groups did not differ in the TBI and background
      characteristics. However, TBI patients with CPTHA had significantly higher HPT
      and lower PPT in the cranium and higher PTSD symptomatology than TBI patients
      without CPTHA and healthy controls. Adaptation to pain and CPM were diminished in
      the CPTHA group compared with the two control groups. The intensity of CPTHA
      correlated negatively with cranial PPT, magnitude of pain adaptation, and CPM.
      CPTHA intensity correlated positively with PTSD symptomatology. CPTHA appears to
      be characterized by cranial hyperalgesia and dysfunctional pain modulation
      capabilities, which are associated with CPTHA magnitude. It is concluded that
      damage to pain modulatory systems along with chronic cranial sensitization
      underlies the development of CPTHA. PTSD may reinforce CPTHA and vice versa.
      Clinical implications are discussed.

PMID- 25068511
TI  - Effect of a virtual environment on the development of mathematical skills in
      children with dyscalculia.
AB  - In this study, we show the effectiveness of a virtual environment comprising 18
      computer games that cover mathematics topics in a playful setting and that can be
      executed on the Internet with the possibility of player interaction through chat.
      An arithmetic pre-test contained in the Scholastic Performance Test was
      administered to 300 children between 7 and 10 years old, including 162 males and
      138 females, in the second grade of primary school. Twenty-six children whose
      scores showed a low level of mathematical knowledge were chosen and randomly
      divided into the control (CG) and experimental (EG) groups. The EG participated
      to the virtual environment and the CG participated in reinforcement using
      traditional teaching methods. Both groups took a post-test in which the
      Scholastic Performance Test (SPT) was given again. A statistical analysis of the
      results using the Student's t-test showed a significant learning improvement for
      the EG and no improvement for the CG (p<=0.05). The virtual environment allows
      the students to integrate thought, feeling and action, thus motivating the
      children to learn and contributing to their intellectual development. 

PMID- 25068514
TI  - Transforming polyethylenimine into a pH-switchable hydrogel by additional
      supramolecular interactions.
AB  - Attaching a self-complementary zwitterionic supramolecular binding site to the
      amino groups of polyethyleneimine leads to a pH switchable hydrogel as
      dimerization of the zwitterions introduces additional crosslinks between the
      polymer chains. This gel responds to both the addition of either acid or base, as
      only the zwitterion can self-assemble but neither the protonated or deprotonated
      form. 

PMID- 25068515
TI  - Correlation of nu(OH) spectral shifts of phenol-benzene O-H...pi hydrogen-bonded
      complexes with donor's acidity: a combined matrix isolation, infrared
      spectroscopy, and quantum chemistry study.
AB  - O-H stretching infrared fundamentals (nuOH) of phenol and a series of
      fluorophenol monomers and their 1:1 complexes with benzene have been measured
      under a matrix isolation condition (8 K). Spectral analysis reveals that ring
      fluorine substitutions have little effect on phenolic nuO-H as long as the
      molecules in the matrix are fully dispersed as monomers. The substitution effects
      are pronouncedly manifested only when the phenols are complexed with benzene, and
      the measured shift in phenolic nuOH from the monomer value varies from ~78 cm(-1)
      in phenol to ~98 cm(-1) in 3,4,5-trifluorophenol. The spectral shifts are found
      to display a linear correlation with the aqueous phase acid dissociation
      constants (pKa) of the phenols. The spectral changes predicted by electronic
      structure calculations at several levels of theory are found to be consistent
      with the observations. Such correlations are also found to exist with respect to
      different energetic, geometric, and other electronic structure parameters of the
      complexes. Atoms in Molecules (AIM) analysis shows a distinct bond critical point
      due to accumulation of electron density at the hydrogen-bonding site. The
      variation of electron densities both on the hydrogen bond as well the donor O-H
      group is in accordance with the experimentally observed nuO-H of the various
      fluorophenol-benzene complexes. Partitioning of binding energies into components
      following the Morokuma-Kitaura scheme shows that the pi-hydrogen-bonded complexes
      are stabilized predominantly by dispersion interactions, although electrostatics,
      polarization, and charge-transfer terms have appreciable contribution to overall
      binding energies. NBO analysis reveals that hyperconjugative charge-transfers
      from the filled pi-orbitals of the hydrogen bond acceptor (benzene) to the
      antibonding sigma*(O-H) orbital of the donors (phenols) display correlations
      which are fully consistent with the observed variations of spectral shifts. The
      analysis also shows that the O-H bond dipole moments of all the phenolic species
      are nearly the same, implying that local electrostatics has only a little effect
      at the site of hydrogen bonding. 

PMID- 25068516
TI  - Resveratrol inhibits breast cancer stem-like cells and induces autophagy via
      suppressing Wnt/beta-catenin signaling pathway.
AB  - Resveratrol, a natural polyphenolic compound, is abundantly found in plant foods
      and has been extensively studied for its anti-cancer properties. Given the
      important role of CSCs (Cancer Stem Cells) in breast tumorigenesis and
      progression, it is worth investigating the effects of resveratrol on CSCs. The
      article is an attempt to investigate the effects of resveratrol on breast CSCs.
      Resveratrol significantly inhibits the proliferation of BCSCs (breast cancer stem
      like cells) isolated from MCF-7 and SUM159, and decreased the percentage of BCSCs
      population, consequently reduced the size and number of mammospheres in non
      adherent spherical clusters. Accordingly, the injection of resveratrol (100
      mg/kg/d) in NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice
      effectively inhibited the growth of xenograft tumors and reduced BCSC population
      in tumor cells. After the reimplantation of primary tumor cells into the
      secondary mice for 30 d, all 6 control inoculations produced tumors, while tumor
      cells derived from resveratrol-treated mice only caused 1 tumor of 6
      inoculations. Further studies by TEM (Transmission electron microscopy) analysis,
      GFP-LC3-II puncta formation assay and western blot for LC3-II, Beclin1 and Atg 7,
      showed that resveratrol induces autophagy in BCSCs. Moreover, resveratrol
      suppresses Wnt/beta-catenin signaling pathway in BCSCs; over-expression of beta
      catenin by transfecting the plasmid markedly reduced resveratrol-induced
      cytotoxicity and autophagy in BCSCs. Our findings indicated that resveratrol
      inhibits BCSCs and induces autophagy via suppressing Wnt/beta-catenin signaling
      pathway. 

PMID- 25068520
TI  - Soluble components of the flagellar export apparatus, FliI, FliJ, and FliH, do
      not deliver flagellin, the major filament protein, from the cytosol to the export
      gate.
AB  - Flagella, the locomotion organelles of bacteria, extend from the cytoplasm to the
      cell exterior. External flagellar proteins are synthesized in the cytoplasm and
      exported by the flagellar type III secretion system. Soluble components of the
      flagellar export apparatus, FliI, FliH, and FliJ, have been implicated to carry
      late export substrates in complex with their cognate chaperones from the
      cytoplasm to the export gate. The importance of the soluble components in the
      delivery of the three minor late substrates FlgK, FlgL (hook-filament junction)
      and FliD (filament-cap) has been convincingly demonstrated, but their role in the
      transport of the major filament component flagellin (FliC) is still unclear. We
      have used continuous ATPase activity measurements and quartz crystal microbalance
      (QCM) studies to characterize interactions between the soluble export components
      and flagellin or the FliC:FliS substrate-chaperone complex. As controls,
      interactions between soluble export component pairs were characterized providing
      Kd values. FliC or FliC:FliS did not influence the ATPase activity of FliI alone
      or in complex with FliH and/or FliJ suggesting lack of interaction in solution.
      Immobilized FliI, FliH, or FliJ did not interact with FliC or FliC:FliS detected
      by QCM. The lack of interaction in the fluid phase between FliC or FliC:FliS and
      the soluble export components, in particular with the ATPase FliI, suggests that
      cells use different mechanisms for the export of late minor substrates, and the
      major substrate, FliC. It seems that the abundantly produced flagellin does not
      require the assistance of the soluble export components to efficiently reach the
      export gate. 

PMID- 25068517
TI  - Role of the C-type lectin receptors MCL and DCIR in experimental colitis.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the
      gastrointestinal tract. Though its exact etiology is still unclear, it is
      proposed that an imbalance in the intestinal homeostasis leads to a disturbed
      interaction between commensal microbiota and the mucosal immune system. Previous
      studies have shown that both innate and adaptive immunity are involved in an
      overwhelming colon inflammation, and thus contribute to the pathogenesis of IBD.
      In innate immunity, several pattern recognition receptors such as Toll-like
      receptors, NOD-like receptors or C-type lectin receptors (CLRs) are involved in
      IBD pathogenesis. Myeloid CLRs are mainly expressed by antigen-presenting cells
      and bind to glycan structures present on self or foreign antigens. The Macrophage
      restricted C-type lectin (MCL) and the Dendritic cell immunoreceptor (DCIR) are
      two poorly characterized members of the CLR family. In this study, we
      investigated the role of MCL and DCIR in the pathogenesis of murine colitis. Both
      CLRs bound to intestinal microbiota to a different extent. They modulated the
      production of pro-inflammatory cytokines by antigen-presenting cells upon
      stimulation with heat-killed microbiota and impacted subsequent T cell responses.
      To analyze whether MCL and DCIR contribute to the pathogenesis of IBD, the
      dextran sulfate sodium (DSS) murine colitis model was employed. MCL-/- as well as
      DCIR-/- mice exhibited only a slightly increased severity of disease compared to
      wild-type mice indicating a limited role for MCL and DCIR in the regulation of
      intestinal immunity. 

PMID- 25068518
TI  - MicroRNA-31 is overexpressed in cutaneous squamous cell carcinoma and regulates
      cell motility and colony formation ability of tumor cells.
AB  - Cutaneous squamous cell carcinoma (cSCC) is a malignancy of epidermal
      keratinocytes that is responsible for approximately 20% of skin cancer-related
      death yearly. We have previously compared the microRNA (miRNA) expression profile
      of cSCC to healthy skin and found the dysregulation of miRNAs in human cSCC. In
      this study we show that miR-31 is overexpressed in cSCC (n = 68) compared to
      healthy skin (n = 34) and precancerous skin lesions (actinic keratosis, n = 12).
      LNA in situ hybridization revealed that miR-31 was specifically up-regulated in
      tumor cells. Mechanistic studies of inhibition of endogenous miR-31 in human
      metastatic cSCC cells revealed suppressed migration, invasion and colony forming
      ability, whereas overexpression of miR-31 induced these phenotypes. These results
      indicate that miR-31 regulates cancer-associated phenotypes of cSCC and identify
      miR-31 as a potential target for cSCC treatment.

PMID- 25068521
TI  - Hypomagnesaemia and hypocalcaemia in a patient with systemic sclerosis: role of
      proton pump inhibitors.
AB  - Proton pump inhibitors (PPI) are widely used in patients with systemic sclerosis
      (SSc) due to the chronic gastroesophageal reflux. The authors report a female
      patient with a 9-year history of SSc and long-term use of omeprazole, who
      complained of paresthesia and asthenia for 12 months. Physical examination
      revealed clinical signs of hypocalcaemia confirmed by laboratory tests that also
      showed hypomagnesaemia. After exclusion of possible causes, hypomagnesaemia
      secondary to PPI was diagnosed and omeprazole was replaced by a histamine H2
      receptor antagonist: ranitidine. Despite continuous magnesium supplementation,
      the reintroduction of PPI at a lower dose due to worsening of dyspeptic symptoms
      led to recurrence of hypomagnesaemia. After definitive suspension of PPI,
      reintroduction of ranitidine and optimisation of anti-reflux environmental
      measures, the patient stabilised. In conclusion, SSc patients using PPIs should
      have their magnesium and calcium serum levels measured periodically, and non
      specific symptoms such as asthenia, generalised paresthesia or life-threatening
      manifestations (seizures, arrhythmias) should not be neglected. 

PMID- 25068523
TI  - Measurement of aortic augmentation index in pregnant women with raised blood
      pressure and subsequent outcomes: a preliminary prospective cohort study.
AB  - OBJECTIVE: Preeclampsia is associated with arterial dysfunction and augmentation
      index (AIX%) is an established indicator of arterial dysfunction. Our aim was to
      investigate the relationship of AIX% with time-to-delivery and other outcomes in
      women admitted to an antenatal triage unit. METHODS: We recruited 28 women with
      singleton pregnancies attending antenatal triage ward for assessment of
      hypertension. After 10 min rest, seated brachial blood pressure (Omron HEM-757)
      and AIX% (SphygmoCor applanation tonometry pulse wave analysis, PWA) were
      measured by a single investigator; other clinicians remained blinded to PWA
      results. Routine assessment included cardiotocography, urine analysis and blood
      tests. Subsequent outcomes were extracted from the obstetric records. RESULTS:
      Mean AIX% was 19.7% (SD 11.5; range -4% to +36%), maternal age 31 years,
      gestation 37 weeks, brachial BP 145/95, proteinuria 39%. Nine women had
      preeclampsia at assessment and six subsequently developed preeclampsia. Median
      time-to-delivery was 10 d (IQR 1.6-25 d) and was shorter for AIX% >= 20% (median
      8.9 versus 19.8 d). AIX% was higher with preeclampsia (24.0%; SD 9.5) versus
      gestational hypertension (15.2%; SD 12.4); absolute difference 8.8% (95%CI 0.1
      17.5; p = 0.05). A one-point higher AIX% (adjusted for age, urate and gestation)
      was associated with 0.3 d (95%CI -0.5 to 0.0; p = 0.06) reduced time-to-delivery.
      A higher AIX% was also associated with induction for preeclampsia, severe
      preeclampsia, peripartum-anti-hypertensives and discharge-on-anti-hypertensives.
      Area under the curve (AUC) for AIX% predicting preeclampsia was 0.80 (95%CI 0.59
      1.00; p = 0.04). CONCLUSION: AIX% is associated with time-to-delivery and other
      outcomes in pregnancy.

PMID- 25068524
TI  - Response to Carbillon L et al. letter titled; "The imbalance of circulating
      angiogenic/anti-angiogenic factors is mild or absent in obese women destined to
      develop preeclampsia".

PMID- 25068525
TI  - Maternal serum apelin and YKL-40 levels in early and late-onset pre-eclampsia.
AB  - OBJECTIVE: The aim of the present study is to investigate whether alterations in
      the serum levels of apelin and YKL-40 differ between early and late onset pre
      eclampsia and whether there is a correlation between apelin and YKL-40 in women
      who subsequently develop early and late pre-eclampsia. MATERIALS AND METHODS: A
      total number of 80 pregnant women, 40 with normal pregnancy and 40 with pre
      eclampsia, were included in the present study. Both the normal pregnant and pre
      eclamptic subjects were subdivided into two groups. Serum YKL-40 and apelin
      concentrations were measured. RESULTS: Mean maternal serum YKL-40 levels were
      both lower in women who subsequently developed early (87.45 +/- 3.07 versus
      103.40 +/- 4.29) or late (96.43 +/- 4.06 versus 99.87 +/- 3.63) pre-eclampsia
      than those who remained normotensive. The difference was significant in early
      onset preeclamptic women (p < 0.05) rather than late-onset pre-eclamptic ones (p
      > 0.05). Mean maternal serum apelin levels were both higher in women who
      subsequently developed early (8.6 +/- 3.6 versus 5.7 +/- 1.2) or late (9.6 +/-
      2.5 versus 8.1 +/- 1.8) pre-eclampsia than those who remained normotensive. The
      difference was significant in early-onset preeclamptic women (p < 0.05) rather
      than late-onset pre-eclamptic ones (p > 0.05). There was a significant negative
      correlation between serum apelin and YKL-40 levels (r = -0.48, p = 0.001).
      CONCLUSION: Circulating levels of apelin are significantly increased in early
      onset pre-eclampsia, indicating the role of apelin in the discrimination of the
      early-onset of pre-eclampsia. On the other hand, maternal serum YKL-40 levels are
      not elavated significantly, indicating that adipose-derived apelin is primarily
      involved in the vascular pathogenesis of early-onset pre-eclampsia than
      macrophage-derived YKL-40.

PMID- 25068526
TI  - Maternal exposure to the production of fireworks and reduced rate of new onset
      hypertension in pregnancy.
AB  - BACKGROUND: Carbon monoxide (CO) is one of the main substances contained in
      fireworks. Previous studies suggested that CO may have protective effect on the
      development of hypertension of pregnancy. METHOD: The authors conducted a
      prospective cohort study in Liuyang, Hunan, China between January 2010 and
      December 2011. Demographic and life-style variables of the participating pregnant
      women were obtained through structured interview with the women and clinical data
      were retrieved from antenatal medical records. Density of fireworks factories was
      defined as the number of fireworks factories per 1000 residents in the township
      where the mothers resided during pregnancy. Multiple logistic regression analysis
      was used to analyze the independent association between maternal exposure to the
      production of fireworks and new onset hypertension in pregnancy. RESULTS: A total
      of 5976 pregnant women were included in the final analysis. Density of fireworks
      factories was inversely correlated with incidence of new onset hypertension in
      pregnancy (Pearson correlation coefficient = -0.29, p < 0.001). Multiple logistic
      regression analysis showed that, compared with women who resided during pregnancy
      in a township with 0-0.25 fireworks factories per 1000 residents, the rates of
      new onset hypertension in pregnancy in women who resided in a township with 0.26
      1.00 fireworks factories per 1000 residents (Odds Ratio = 0.66, 95% confidence
      interval: 0.46, 0.96) and >1.5 fireworks factories per 1000 residents (Odds Ratio
      = 0.65, 95% confidence interval: 0.44, 0.97) were reduced by more than 30%.
      CONCLUSION: Maternal exposure to the high density of fireworks factories is
      associated with reduced risk of developing new onset hypertension in pregnancy.

PMID- 25068527
TI  - Influence of the electronic configuration in the properties of d6-d5 mixed
      valence complexes.
AB  - We report here the spectroscopic properties of four very closely related mixed
      valence cyanide-bridged bimetallic complexes, trans-[Ru(T)(bpy)(MU
      NC)Ru(L)4(CN)](3+) (T = tris(1-pyrazolyl)methane (tpm, a) or 2,2';6',2"
      terpyridine, (tpy, b), and L = pyridine (py, 1) or 4-methoxypyridine (MeOpy, 2)).
      In acetonitrile all the complexes present intervalence charge transfer (IVCT)
      transitions in the NIR region, but their intensities are widely different, with
      the intensity of the transition observed for 1a-b(3+) around four times larger
      than that observed for 2a-b(3+). This contrasting behavior can be traced to the
      different nature of the dpi acceptor orbitals involved in these transitions, as
      confirmed by (TD)DFT calculations. The spectroscopy of 1a-b(3+) provides evidence
      that the spin density is delocalized over the two ruthenium ions, such as a
      narrowing of the IVCT bands that results in the resolution of the expected three
      bands, and a weak solvent dependence of the energy of these transitions. The
      spectroscopy of 2a-b(3+) instead indicates that the spin density is localized on
      one ruthenium ion. The IVCT in these systems is particularly weak due to the
      configuration of the Ru(III), where the vacant orbital is perpendicular to the
      cyanide bridge. 

PMID- 25068528
TI  - Indium-mediated asymmetric intramolecular allenylation of N-tert-butanesulfinyl
      imines: efficient and practical access to chiral 3-allenyl-4-aminochromanes.
AB  - An efficient method for the preparation of highly optically active 3-allenyl- and
      3-vinyl-4-aminochromanes by In-mediated intramolecular cyclization has been
      developed. The synthetic utilities of the approach were demonstrated by the
      construction of various chiral polycyclic heterocycles, especially the
      interesting spiroheterocyclic compound 9 and steroid analogue 10. 

PMID- 25068529
TI  - Evidence-based nurse-driven interventions for the care of newborns with neonatal
      abstinence syndrome.
AB  - Neonatal abstinence syndrome (NAS) is a growing problem in the United States,
      related to increased maternal substance use and abuse, and a set of drug
      withdrawal symptoms that can affect the central nervous system and
      gastrointestinal and respiratory systems in the newborn when separated from the
      placenta at birth. Infants with NAS often require a significant length of stay in
      the neonatal intensive care unit (NICU). Pharmacologic treatments and physician
      directed interventions are well researched, but nursing-specific interventions
      and recommendations are lacking. A thorough review and analysis of the literature
      and interviews with neonatal experts guided the development of a nursing clinical
      practice guideline for infants with NAS in a level IV NICU. Recommended nursing
      specific interventions include methods for maternal drug-use identification,
      initiation and timing of the Finnegan Scoring System to monitor withdrawal
      symptoms, and bedside interventions to lessen the drug-withdrawal symptoms in the
      newborn with NAS. 

PMID- 25068530
TI  - Bis(imino)pyridine cobalt-catalyzed dehydrogenative silylation of alkenes: scope,
      mechanism, and origins of selective allylsilane formation.
AB  - The aryl-substituted bis(imino)pyridine cobalt methyl complex, ((Mes)PDI)CoCH3
      ((Mes)PDI = 2,6-(2,4,6-Me3C6H2-N?CMe)2C5H3N), promotes the catalytic
      dehydrogenative silylation of linear alpha-olefins to selectively form the
      corresponding allylsilanes with commercially relevant tertiary silanes such as
      (Me3SiO)2MeSiH and (EtO)3SiH. Dehydrogenative silylation of internal olefins such
      as cis- and trans-4-octene also exclusively produces the allylsilane with the
      silicon located at the terminus of the hydrocarbon chain, resulting in a highly
      selective base-metal-catalyzed method for the remote functionalization of C-H
      bonds with retention of unsaturation. The cobalt-catalyzed reactions also enable
      inexpensive alpha-olefins to serve as functional equivalents of the more valuable
      alpha, omega-dienes and offer a unique method for the cross-linking of silicone
      fluids with well-defined carbon spacers. Stoichiometric experiments and deuterium
      labeling studies support activation of the cobalt alkyl precursor to form a
      putative cobalt silyl, which undergoes 2,1-insertion of the alkene followed by
      selective beta-hydrogen elimination from the carbon distal from the large
      tertiary silyl group and accounts for the observed selectivity for allylsilane
      formation. 

PMID- 25068531
TI  - The effect of nanoemulsion as a carrier of hydrophilic compound for transdermal
      delivery.
AB  - The purpose of the present study was to investigate the effect of nanoemulsions
      as a carrier vehicle of hydrophilic drug for transdermal delivery. The response
      surface methodology with a mixture design was used to evaluate the effect of
      ingredient levels of nanoemulsion formulations including cosurfactant (isopropyl
      alcohol, 20 ~ 30%), surfactant (mixed of Brij 30 and Brij 35, 20 ~ 30%), and
      distilled-water (34.5 ~ 50.0%) on properties of the drug-loaded nanoemulsions
      including physicochemical characters and drug permeability through rat skin. The
      result showed that the hydrophilic drug in aqueous solution with or without
      penetration enhancer could not transport across rat skin after 12 h of
      application. Used nanoemulsions as carrier vehicle, the permeation rate of drug
      was significantly increased from 0 to 63.23 ug/cm2/h and the lag time was
      shortened from more than 12 h to about 2.7 ~ 4.0 h. Moreover, the drug-loaded
      nanoemulsion formulation also showed physicochemical stability after 3 month
      storage at 25 degrees C and 40 degrees C.

PMID- 25068532
TI  - Fibronectin module FN(III)9 adsorption at contrasting solid model surfaces
      studied by atomistic molecular dynamics.
AB  - The mechanism of human fibronectin adhesion synergy region (known as integrin
      binding region) in repeat 9 (FN(III)9) domain adsorption at pH 7 onto various and
      contrasting model surfaces has been studied using atomistic molecular dynamics
      simulations. We use an ionic model to mimic mica surface charge density but
      without a long-range electric field above the surface, a silica model with a long
      range electric field similar to that found experimentally, and an Au {111} model
      with no partial charges or electric field. A detailed description of the
      adsorption processes and the contrasts between the various model surfaces is
      provided. In the case of our model silica surface with a long-range electrostatic
      field, the adsorption is rapid and primarily driven by electrostatics. Because it
      is negatively charged (-1e), FN(III)9 readily adsorbs to a positively charged
      surface. However, due to its partial charge distribution, FN(III)9 can also
      adsorb to the negatively charged mica model because of the absence of a long
      range repulsive electric field. The protein dipole moment dictates its
      contrasting orientation at these surfaces, and the anchoring residues have
      opposite charges to the surface. Adsorption on the model Au {111} surface is
      possible, but less specific, and various protein regions might be involved in the
      interactions with the surface. Despite strongly influencing the protein mobility,
      adsorption at these model surfaces does not require wholesale FN(III)9
      conformational changes, which suggests that the biological activity of the
      adsorbed protein might be preserved. 

PMID- 25068533
TI  - Immune response to intrapharyngeal LPS in neonatal and juvenile mice.
AB  - Neonates and infants have a higher morbidity and mortality associated with lower
      respiratory tract illnesses compared with older children. To identify age-related
      and longitudinal differences in the cellular immune response to acute lung injury
      (ALI), neonatal and juvenile mice were given Escherichia coli LPS using a novel,
      minimally invasive aspiration technique. Neonatal and juvenile mice received
      between 3.75 and 7.5 mg/kg LPS by intrapharyngeal aspiration. Airway and lung
      cells were isolated and characterized by flow cytometry, cytokine/chemokine mRNA
      expression from lung homogenates was quantified, and lung morphometry and injury
      scores were performed. LPS-treated neonatal mice underwent adoptive transfer with
      adult T regulatory cells (Tregs). After LPS aspiration, lung monocytes isolated
      from neonatal mice had a predominant M2 phenotype, whereas lung monocytes from
      juvenile mice displayed a mixed M1/M2 phenotype. At 72 hours after LPS exposure,
      neonatal lungs were slower to resolve inflammation and expressed lower mRNA
      levels of CCL2, CCL5, CXCL10, and IL-10. Juvenile, but not neonatal, mice
      demonstrated a significant increase in airway Tregs after LPS exposure. Adoptive
      transfer of adult Tregs into LPS-challenged neonatal mice resulted in reduced
      lung inflammation and improved weight gain. These findings underscore several
      vulnerabilities in the neonatal immune response to LPS-induced ALI. Most striking
      was the deficiency in airway Tregs after LPS aspiration. Adoptive transfer of
      adult Tregs mitigated LPS-induced ALI in neonatal mice, highlighting the
      importance of age-related differences in Tregs and their response to ALI during
      early postnatal development. 

PMID- 25068534
TI  - Towards understanding the stabilization process in vermicomposting using PARAFAC
      analysis of fluorescence spectra.
AB  - In this study, fluorescence excitation-emission matrix (EEM) combined with
      parallel factor analysis (PARAFAC) was employed to trace the behavior of water
      extractable organic matter and assess the stabilization process during
      vermicomposting of sewage sludge and cattle dung. Experiments using different
      mixing ratios of sewage sludge and cattle dung were conducted using Eisenia
      fetida. The results showed that vermicomposting reduced the DOC, DOC/DON ratio
      and ammonia, while increased the nitrate content. A three-component model
      containing two humic-like materials (components 1 and 2) and a protein-like
      material (component 3) was successfully developed using PARAFAC analysis.
      Moreover, the initial waste composition had a significant effect on the
      distribution of each component and the addition of cattle dung improved the
      stability of sewage sludge in vermicomposting. The PARAFAC results also indicated
      that protein-like materials were degraded and humic acid-like compounds were
      evolved during vermicomposting. Pearson correlation analysis showed that
      components 2 and 3 are more suitable to assess vermicompost maturity than
      component 1. In all, EEM-PARAFAC can be used to track organic transformation and
      assess biological stability during the vermicomposting process. 

PMID- 25068535
TI  - Environmental relative moldiness index and associations with home characteristics
      and infant wheeze.
AB  - Possible relationships between mold contamination, as described by the
      Environmental Relative Moldiness Index (ERMI), home characteristics, and the
      development of wheeze in the first year of life were evaluated among a cohort of
      urban infants (n = 103) in Syracuse, New York. Pregnant women with a history of
      asthma were recruited in 2001-2002 for the "Assessment of Urban Dwellings for
      Indoor Toxics" (AUDIT) study. When the infants were approximately 3 months of
      age, a home inspection was carried out and indoor environmental samples
      collected, including vacuumed house dust. ERMI levels in the Syracuse cohort
      homes were higher than the U.S. average, with an overall mean of 11.4. ERMI
      levels were significantly higher in homes with visible water problems (p = 0.023)
      and visible mold (p = 0.023). ERMI levels in apartments were significantly lower
      than the values measured in houses (p = 0.0003). While infants experiencing
      wheeze (38%) tended to live in homes with higher ERMI values than those without
      wheeze (ERMI values of 12.3 and 10.9, respectively), the differences did not
      reach statistical significance. A subset analysis limited to infants with living
      room samples who remained in the same home during the study (n = 25) was
      suggestive of an association between higher ERMI values and wheeze (p = 0.10). In
      summary, the ERMI is a standardized metric which allows for comparison of
      moldiness levels in homes across studies and regions in the United States. ERMI
      levels in Syracuse homes were skewed to the high end of the national scale.
      Higher ERMI levels were indicators of water problems, mold, and type of housing. 

PMID- 25068536
TI  - Memories of traumatic events in childhood fade after experiencing similar less
      stressful events: results from two natural experiments.
AB  - The long-term stability of youth reports of traumatic events is largely unknown.
      Translational animal research suggests that there may be an alteration of
      memories for traumatic events via memory reconsolidation processes, whereas
      clinical research suggests memory alteration may occur through augmentation by
      negative emotions. In this report, 2 natural experiments test reconsolidation
      model and augmentation model predictions about the course of traumatic memories
      in youth. Data are from 2 prospective studies that assessed reports of an initial
      traumatic event (Hurricane Katrina) and tested recall both pre and post a similar
      event (Hurricane Gustav). In the 1st (Sample 1; n = 94, initial Grade 9 followed
      to 11), youth were assessed at 4 time points: Times 1-3 were 13, 20, and 26
      months post-Katrina and then Time 4 was 5 months post-Hurricane Gustav. In the
      2nd (Sample 2; n = 141, Grades 4 through 8), youth were assessed at 12 months pre
      Gustav (Time 1; 24 months post-Katrina) and then again at 1 month (Time 2) and 8
      months (Time 3) post-Gustav. Those with relatively high Gustav exposure showed
      more stability in their reports of Katrina exposure events, whereas in those with
      low Gustav exposure, reports of Katrina events decreased. Time spans between
      recall, age, gender, symptoms of posttraumatic stress disorder, or
      cognitive/learning ability did not explain changes in the reports. The study
      provides the 1st long-term data on the consistency of youth reports of disaster
      related experiences and provides initial evidence for the ecological validity of
      memory reconsolidation theory applied to traumatic events in youth.

PMID- 25068539
TI  - Macroporous microcarriers for introducing cells into a microfluidic chip.
AB  - Macroporous gelatin beads (CultiSpherTM microcarriers) provide a convenient
      method for rapidly and reliably introducing cells cultured ex situ into a
      microfluidic device, where the spheres create a 3D environment for continued cell
      proliferation. We demonstrate the usefulness of this technique with a proof-of
      concept viability analysis of cardiac cells after treatment with doxorubicin. 

PMID- 25068538
TI  - A standardized blood test for the routine clinical diagnosis of impaired GM-CSF
      signaling using flow cytometry.
AB  - Impaired signaling by granulocyte/macrophage-colony stimulating factor (GM-CSF)
      drives the pathogenesis of two diseases (autoimmune and hereditary pulmonary
      alveolar proteinosis (PAP)) representing over ninety percent of patients who
      develop PAP syndrome but not a broad spectrum of diseases that cause PAP by other
      mechanisms. We previously exploited the ability of GM-CSF to rapidly increase
      cell-surface CD11b levels on neutrophils (CD11bSurface) to establish the CD11b
      stimulation index (CD11b-SI), a test enabling the clinical research diagnosis of
      impaired GM-CSF signaling based on measuring CD11bSurface by flow cytometry using
      fresh, heparinized blood. (CD11b-SI is defined as GM-CSF-stimulated- CD11bSurface
      minus unstimulated CD11bSurface divided by un-stimulated CD11bSurface multiplied
      by 100.) Notwithstanding important and unique diagnostic utility, the test is
      sensitive to experimental conditions that can affect test performance. The
      present study was undertaken to optimize and standardize CD11b-SI test for
      detecting impaired GM-CSF signaling in heparinized human blood specimens from PAP
      patients. Results demonstrated the test was sensitive to choice of anticoagulant,
      pretesting incubation on ice, a delay between phlebotomy and test performance of
      more than one hour, and the concentration GM-CSF used to stimulate blood. The
      standardized CD11b-SI test reliably distinguished blood specimens from autoimmune
      PAP patients with impaired GM-CSF signaling from those of health people with
      normal signaling. Intra-subject differences were smaller than inter-subject
      differences in repeated measures. Receiver operating characteristic curve
      analysis identified a CD11b-SI test result of 112 as the optimal cut off
      threshold for diagnosis of impaired GM-CSF signaling in autoimmune PAP for which
      the sensitivity and specificity were both 100%. These results support the use of
      this standardized CD11b-SI for routine clinical identification of impaired GM-CSF
      signaling in patients with autoimmune PAP. The CD11b-SI may also have utility in
      clinical trials of novel therapeutic strategies targeting reduction in GM-CSF
      bioactivity now under evaluation for multiple common autoimmune and inflammatory
      disorders. 

PMID- 25068540
TI  - A systematic review of calcium channel blocker use and cognitive decline/dementia
      in the elderly.
AB  - OBJECTIVE: Treating hypertension in those aged at least 80 years is now
      recommended; however, the best antihypertensive to choose remains unexplored.
      Calcium channel blocker (CCB) use has been associated with a decreased risk of
      incident dementia in a younger hypertensive group but with an increased risk of
      cognitive decline in the very elderly. Either result could have a large impact on
      a vulnerable population. The aim of this review was to assess the evidence
      relating CCB use to later cognitive decline or dementia in the very elderly.
      METHODS: A systematic review of the literature was carried out. The databases
      Medline, PubMed, Embase and Psychinfo were searched from 1980 to 22 August 2013.
      Abstracts were reviewed by two independent reviewers and papers meeting the
      inclusion criteria were extracted. RESULTS: One thousand, nine hundred and sixty
      eight records were reviewed and 10 articles reporting on nine studies retained
      and extracted. Data were primarily from cohort studies. Only one reported a
      randomized controlled trial comparing CCBs with placebo. Populations, comparator
      groups, follow-up times, outcomes and exposure varied and overall results were
      mixed. It was not possible to combine all studies, but those reporting
      Alzheimer's disease outcomes were combined to produce an overall risk ratio of
      0.79 (95% confidence interval 0.53-1.17). CONCLUSION: At present, there is no
      clear evidence to suggest that CCB use increases or decreases risk of cognitive
      decline or dementia in the very elderly. A robust clinical trial is now required
      to resolve this.

PMID- 25068541
TI  - World Health Organization authorities promote greater attention and action on
      palliative care.

PMID- 25068542
TI  - The origins of cyanobactin chemistry and biology.
AB  - The correct structure of the symmetrical cyanobactin, ascidiacyclamide, was
      published in Chemical Communications by Hamamoto et al. in 1983. The cyanobactin
      family of compounds are cyclic peptides with modifications including
      azole/azoline rings, D-stereocentres and in some cases prenyl groups. Although
      related compounds were isolated earlier by Ireland et al., two of the three
      published structures later had to be corrected. Hamamoto's ascidiacyclamide
      structure assisted the understanding of the chemistry, bioactivity, biological
      origin and biosynthesis of this group of compounds. Cyanobactins are of interest
      as new chemotypes for the treatment of a range of diseases, in particular those
      in which extended binding sites are implicated.

PMID- 25068543
TI  - Updated international clinical recommendations on scar management: part 1-
      evaluating the evidence.
AB  - BACKGROUND: There is an ongoing need to standardize scar management by
      establishing safe and effective treatment options that can be applied in routine
      clinical practice. OBJECTIVE: To review available data on methods for preventing
      and treating cutaneous scarring. MATERIALS AND METHODS: Relevant scientific
      literature was identified through a comprehensive search of the MEDLINE database.
      Additional data and published studies were submitted for consideration by members
      of the International Advisory Panel on Scar Management. RESULTS: One of the most
      significant advances in scar management over the past 10 years has been the
      broader application of laser therapy, resulting in a shift in status from an
      emerging technology to the forefront of treatment. Accumulated clinical evidence
      also supports a greater role for 5-fluourouracil in the treatment of hypertrophic
      scars and keloids, particularly in combination with intralesional
      corticosteroids. Encouraging data have been reported for newer therapies,
      including bleomycin, onion extract-containing preparations, imiquimod, and
      mitomycin C, although methodologic limitations in available studies merit
      consideration. In general, clinical and aesthetic outcomes seem to be enhanced by
      a combination approach to treatment. CONCLUSION: Advances in therapeutic options
      and new study data necessitate a revision of algorithms for the prevention and
      management of cutaneous scarring.

PMID- 25068544
TI  - Updated international clinical recommendations on scar management: part 2-
      algorithms for scar prevention and treatment.
AB  - BACKGROUND: In 2002, an international advisory panel was convened to assess the
      scientific literature and develop evidence-based guidance for the prevention and
      treatment of pathologic scarring. Emerging clinical data, new treatment options,
      and technical advances warranted a renewed literature search and review of the
      initial advisory panel recommendations. OBJECTIVE: To update the management
      algorithm for pathologic scarring to reflect best practice standards at present.
      MATERIALS AND METHODS: Management recommendations were derived from clinical
      evidence amassed during a comprehensive literature search and from the clinical
      experience and consensus opinion of advisory panel members. RESULTS: A
      combination approach using multiple modalities provides the maximum potential for
      successful treatment of hypertrophic scars and keloids. The advisory panel
      advocates a move toward more aggressive initial management of keloids, including
      earlier application of 5-fluorouracil. A growing body of clinical research
      supports a place in therapy for newer agents (e.g., bleomycin, onion extract,
      imiquimod, mitomycin C) and laser therapy (pulsed-dye, fractional) for scar
      management. CONCLUSION: Prevention and treatment of pathologic scarring requires
      individualized care built upon the principles of evidence-based medicine and
      continues to evolve in step with technological and scientific advances.

PMID- 25068545
TI  - Treatment of axillary osmidrosis using a laser with a 1,444-nm wavelength.
AB  - BACKGROUND: Lasers have been proposed as an alternative treatment for axillary
      osmidrosis. OBJECTIVE: This study aimed to investigate the use of a
      neodymium:yttrium-aluminum-garnet laser with a wavelength of 1,444 nm for
      treating axillary osmidrosis. MATERIALS AND METHODS: Eighteen patients with
      axillary osmidrosis who underwent an operation with a 1,444-nm wavelength laser
      were included in this study. Operative parameters were as follows: pulse = 40 Hz
      and energy = 170 mJ. Total energy was approximately 2,000 to 3,400 J, and the
      operation time was 45 minutes. RESULTS: Statistically significant differences in
      the degree of malodor evaluated by both the patients (p = .001) and doctors (p =
      .012) were detected between preoperative and 6-month postoperative assessments.
      Sweat area was significantly reduced 6 months after the operation compared with
      preoperative values. Postoperative pain had subsided at day 7 in all but 1
      patient. Two patients (11.1%) experienced superficial second-degree burns on the
      unilateral axilla; these burns were resolved fully. CONCLUSION: The laser with a
      wavelength of 1,444 nm was found to be a reliable method for the treatment of
      axillary osmidrosis, with advantages such as small wound size, rapidity of the
      procedure, inconspicuous scars, and speedy recovery and return to normal daily
      activities.

PMID- 25068546
TI  - Q-switched Nd: YAG laser versus trichloroacetic acid peeling in the treatment of
      melasma among Egyptian patients.
AB  - BACKGROUND: Melasma is a common disorder of facial hyperpigmentation that is
      often resistant to treatment. OBJECTIVE: To evaluate the efficacy of
      trichloroacetic acid (TCA) peeling in comparison with double frequency Q-switched
      neodymium-doped:yttrium aluminum garnet (QS-Nd:YAG) laser in the treatment of
      melasma. PATIENTS AND METHODS: Sixty-five adult Egyptian female patients with
      melasma were enrolled in this study. Wood light was used for determination of the
      histological type of melasma. The patients were divided into 4 groups according
      to treatment modalities: peeling with different concentrations of TCA and double
      frequency QS-Nd:YAG laser. Trichloroacetic acid peeling was performed every 2
      weeks up to 8 sessions, whereas laser treatment was performed every month up to 6
      sessions. Melasma area and severity index (MASI) score was used before and after
      treatment for evaluation. RESULTS: Improvement percentage of MASI score was
      significantly higher among patients treated with TCA 25% (p < .001). Epidermal
      type of melasma was significantly improved compared with the dermal type (p =
      .0029). Q-switched neodymium-doped:yttrium aluminum garnet laser showed the
      highest incidence of postinflammatory hyperpigmentation (53.3%). CONCLUSION:
      Trichloroacetic acid peeling is effective in the treatment of melasma, TCA 25%
      was the most effective concentration. Q-switched neodymium-doped:yttrium aluminum
      garnet laser is not recommended in the treatment of melasma because it was
      associated with the highest incidence of complications.

PMID- 25068547
TI  - Evaluation of 70% glycolic peels versus 15% trichloroacetic peels for the
      treatment of photodamaged facial skin in aging women.
AB  - BACKGROUND: Chronic solar irradiation results in both morphological and
      functional changes in affected skin. Superficial peels have been shown to improve
      all symptoms of photodamaged skin. OBJECTIVE: This study was designed to compare
      the efficacy and tolerability of glycolic acid (GA, 70%) with trichloroacetic
      acid (TCA, 15%) for the treatment of photoaging. MATERIALS AND METHODS: Twenty
      female patients affected by photodamage were treated with graded concentrations
      of 70% GA and 15% TCA peel. Each patient was submitted to 5 sessions of these
      peels, with an interval of 14 days between each session. Four clinical parameters
      of surface evaluation of the living skin (hydration, elasticity, melanin, and
      erythema) were measured. The records were made before each treatment and 3 months
      after the last application. RESULTS: The statistical significance in each group
      of patients was observed with elasticity and hydration. Decrease in melanin
      content in the skin occurred significantly after the application of a series of
      treatments with GA. Increase in severity of erythema showed statistical
      significance after the treatment with TCA. CONCLUSION: Superficial peels, such as
      70% GA and 15% TCA, proved to be an effective treatment modality for photodamaged
      facial skin. Both acids contribute to improvement of the photodamaged skin's
      parameters. Glycolic acid increases skin's hydration faster.

PMID- 25068548
TI  - Earlobe freedom clamp.

PMID- 25068550
TI  - Mesoporous CoO nanocubes @ continuous 3D porous carbon skeleton of rose-based
      electrode for high-performance supercapacitor.
AB  - Supercapacitors have attracted lots of attentions for energy storage because of
      their outstanding electrochemical properties, and various kinds of carbon
      materials have been used to improve the performance. In this work, we
      innovatively elevate a natural rose-based continuous 3D porous carbon skeleton.
      The as-prepared carbon skeleton is graphited to some extent and possesses
      hierarchical interconnected 3D porous structures, providing a high electrical
      conductive and electrolyte easy-infiltrated substrate for the fabrication of
      ideal monolithic composite electrodes. Then, we utilized it as scaffold to
      prepare mesoporous CoO nanocubes @ continuous 3D porous carbon skeleton of rose
      composite-based electrode for supercapacitor via hydrothermal approach. The
      obtained material exhibits a noticeable pseudocapacitive performance with a
      brilliant capacitance of 1672 F/g at 1 A/g and as high as 521 F/g at 40 A/g. It
      also should be noted that ~82% of the capacitance was maintained after 3000
      cycles at 5 A/g, and only 40% capacitance loss after 1500 cycles at a relatively
      high current density of 10 A/g. 

PMID- 25068549
TI  - Carbonaceous particles reduce marine microgel formation.
AB  - An increase in ambient carbonaceous particle (CNP) levels has been found,
      potentially leading to significant environmental/health hazards. These particles
      will ultimately enter the oceanic environment and interact with dissolved organic
      carbon. However, a detailed mechanistic understanding of their behavior,
      transport, and fate in marine systems is still much needed. This study, using
      carbon black (CB, 14 nm) nanoparticles as a model, aimed to investigate the
      impact of CNPs on marine microgel formation, a critical shunt between DOC and
      particulate organic carbon that potentially represents a ~70-Gt organic carbon
      flux. We found that CB can enhance the stability of DOC polymers and reduce
      microgel equilibrium sizes in concentration as low as 1 MUgL(-1) CB, possibly due
      to negative surface charges on CB that decrease cross-linking bridges through
      Ca(2+) bonds. The reduction of marine microgel formation induced by CB could lead
      to a decrease in the downward transportation of microbial substrates and
      nutrients, and therefore, could have a significant impact on the carbon cycle and
      the marine ecosystem.

PMID- 25068552
TI  - How spirituality is understood and taught in New Zealand medical schools
      CORRIGENDUM.

PMID- 25068551
TI  - Ratiometric fluorescent biosensor for hyaluronidase with hyaluronan as both
      nanoparticle scaffold and substrate for enzymatic reaction.
AB  - Hyaluronidases (HAase) are involved in various physiological and pathological
      processes and have been reported as urinary marker for bladder cancer. In this
      study, a novel ratiometric fluorescent sensing system based on both aggregation
      induced emission (AIE) and aggregation-induced quenching (ACQ) was developed to
      quantitatively assess hyaluronidase level. First, a tetraphenylethylene
      derivative with positive charges (TPE-2N(+), typical AIE molecule) at both ends
      and an anthracene derivative with positive charge at one end (AN-N(+), typical
      ACQ molecule) was synthesized. These two positively charged compounds were then
      mixed with a negatively charged hyaluronan (HA), which induced the aggregation of
      the compounds as well as the nanoparticles formation as a result of electrostatic
      complexation, with TPE-2N(+) acting as cross-linking agent. The aggregation also
      caused the efficient quenching of the emission of AN-N(+) due to ACQ effect, as
      well as the fluorescence enhancement of TPE-2N(+) due to AIE effect. In the
      presence of HAase, the enzymatic reaction led to the degradation of HA and
      triggered disassembly of the nanoparticles; as a result, the emission of AN-N(+)
      was restored and that of TPE-2N(+) was suppressed. This fluorescence variation
      affords the system a robust ratiometric biosensor for HAase, and the ratio of
      fluorescence intensity for AN-N(+) (I414) to that for TPE-2N(+) (I474) can be
      used as the sensing signal for detecting HAase activity. In this system,
      hyaluronan serves not only as the scaffold for nanoparticle formation but also as
      the substrate for enzymatic reaction. This assay system is operable in aqueous
      media with very low detection limit of 0.0017 U/mL and is capable of detecting
      HAase in biological fluids such as serum and urine. This strategy may provide a
      new and effective approach for developing other enzyme assays. 

PMID- 25068553
TI  - The superior cycle and rate performance of a novel sulfur cathode by immobilizing
      sulfur into porous N-doped carbon microspheres.
AB  - A novel composite of sulfur immobilized into porous N-doped carbon microspheres
      (NCMSs-S) was synthesized. This composite cathode for lithium-sulfur batteries
      delivers a high specific capacity and superior rate capability and cycle
      stability, with a reversible capacity of ~605 mA h g(-1) at 2 C and 85% capacity
      retention after 500 cycles.

PMID- 25068554
TI  - Is stillbirth associated with long-term atherosclerotic morbidity?
AB  - OBJECTIVE: The purpose of this study was to investigate whether women who
      experienced at least 1 stillbirth are at increased risk for subsequent maternal
      long-term atherosclerotic morbidity. STUDY DESIGN: We conducted a population
      based study that compared the incidence of long-term atherosclerotic morbidity in
      a cohort of women with and without previous stillbirth. Deliveries occurred
      during a 25-year period. Patients with known cardiovascular or renal disease
      before the index pregnancy were excluded from the study. Kaplan-Meier survival
      curves were used to estimate the cumulative incidence of cardiovascular- and
      renal-related hospitalizations. Cox proportional hazards models were used to
      estimate the adjusted hazards ratio for cardiovascular- and renal-related
      hospitalizations. RESULTS: Of 99,280 deliveries that met the inclusion criteria,
      1879 deliveries (1.9%) occurred in patients who had had at least 1 stillbirth.
      After stillbirth, patients had a significantly higher cumulative incidence of
      cardiovascular and renal morbidity (Kaplan-Meier survival curve). During the
      follow-up period, patients with at least 1 stillbirth had higher rates of total
      cardiovascular and renal hospitalizations and had higher rates of simple and
      complex cardiovascular events. A significant stepwise increase was found between
      the number of stillbirths and future risk for cardiovascular morbidity. In a Cox
      proportional hazards model that was adjusted for confounders, previous stillbirth
      was associated independently with atherosclerotic morbidity. CONCLUSION:
      Stillbirth is an independent risk factor for long-term maternal atherosclerotic
      morbidity. The risk is higher for patients with recurrent episodes of stillbirth.

PMID- 25068555
TI  - Outcomes from ultrasound follow-up of small complex adnexal masses in women over
      50.
AB  - OBJECTIVE: The discovery of a complex adnexal mass in an older woman often raises
      concern for cancer. We evaluate outcomes for a large population-based cohort of
      women older than age 50 years with a small complex adnexal mass reported on
      ultrasound, without elevated CA125 or other evidence of malignancy, including
      time to detection of malignancy and stage at diagnosis for those initially
      observed. STUDY DESIGN: Women older than age 50 years who had an ultrasound
      during 2007-2011 reporting a complex adnexal mass 1-6 cm in size were identified.
      Previous or subsequent pelvic ultrasounds were reviewed to determine when the
      mass was first identified and whether there was change over time. Women with
      concurrent elevated CA125, evidence of metastatic disease, or less than 24 months
      of clinical follow-up were excluded. Surgical pathology from removal and
      diagnoses of ovarian cancer within 24 months of follow-up were identified.
      RESULTS: Among 1363 complex masses identified, 18 cancers or borderline tumors
      (1.3%; 95% confidence interval, 0.8-2.1%) were found. Six cases were diagnosed
      among 204 women who had immediate surgery after initial ultrasound (15%), and 12
      additional cases were found among 994 women with at least 1 repeat ultrasound
      (73%). Growth was apparent on ultrasound by 7 months for all borderline and
      epithelial ovarian cancers. Of the 12 cases diagnosed during follow-up, 10 were
      found to be stage 1 at surgery. CONCLUSION: Among isolated adnexal masses
      reported as complex and 1-6 cm on pelvic ultrasound in women older than 50 years,
      the overall risk of malignancy is low. All cases of epithelial cancer and
      borderline tumor demonstrated growth by 7 months of observation.

PMID- 25068556
TI  - Impact of robotic technology on hysterectomy route and associated implications
      for resident education.
AB  - OBJECTIVE: We sought to compare the proportion of benign hysterectomies performed
      vaginally and the mean number of hysterectomies with resident involvement by
      route before and after robot implementation. STUDY DESIGN: This multicenter,
      retrospective cohort study using nonsynchronous controls was conducted through
      the Society of Gynecologic Surgeons Fellows' Pelvic Research Network. The route
      of hysterectomy for benign disease was compared for 1-year periods before
      (prerobot) and after (postrobot) robotic introduction at 4 academic institutions.
      We reviewed medical records and recorded patient demographics, hysterectomy
      approach, preoperative and postoperative diagnosis, and resident involvement.
      RESULTS: In all, 1440 hysterectomies were included: 732 in the prerobot group and
      708 in the postrobot group. Median age was 46 years and mean body mass index was
      29.5 (standard deviation, 6.9). The proportion of hysterectomies performed via
      the vaginal route decreased from 42.5% prerobot to 30.5% postrobot (P < .0001)
      and via the abdominal route from 22.1% prerobot to 16.5% postrobot (P = .001).
      The proportion of hysterectomies performed laparoscopically increased from 1.6%
      prerobot to 11.9% postrobot (P < .0001). At a mean of 2.3 years after
      introduction of the robot into an institution, hysterectomies performed using
      robotic assistance accounted for 23.3% of hysterectomies for benign disease. Mean
      uterine weight was similar in the prerobot and postrobot groups. Resident
      involvement in all hysterectomies done via all routes other than robotic
      increased from 81.0% prerobot to 88.6% postrobot; however, residents were
      involved in only 58.9% of robotic hysterectomies. CONCLUSION: The proportion of
      hysterectomies performed vaginally has significantly decreased since the adoption
      of robotic technology at institutions included in this study. The proportion of
      hysterectomies with resident involvement is lower with a robotic approach than
      any other route.

PMID- 25068557
TI  - Venous thromboembolism in reconstructive pelvic surgery.
AB  - OBJECTIVE: We sought to determine the incidence and risk factors for venous
      thromboembolism (VTE) in women undergoing reconstructive pelvic surgery (RPS).
      STUDY DESIGN: Using the American College of Surgeons National Surgical Quality
      Improvement Program registry, we identified patients who underwent RPS from 2006
      through 2010 based on Current Procedural Terminology codes. We defined 2 cohorts:
      women with any RPS performed, with concomitant surgery from other specialties
      allowed (RPS + other), and women whose only procedure was RPS. VTE was defined as
      deep vein thrombosis or pulmonary embolism diagnosed within 30 days of surgery.
      Demographic characteristics, comorbidities, and operative characteristics were
      extracted from the database. Variables were analyzed using chi(2) tests and
      Student t tests for categorical and continuous variables. We performed a multiple
      logistic regression to control for confounding variables. RESULTS: In all, 20,687
      women underwent RPS + other, with 69 cases of VTE for a rate of 0.3%.
      Multivariate analysis demonstrated predictors for postoperative VTE including
      inpatient hospital status (odds ratio [OR], 7.69; P < .001), higher American
      Society of Anesthesiology Physical Status classification (OR, 2.70; P < .001),
      and emergency intervention (OR, 3.65; P = .008). When women undergoing only RPS
      were analyzed, there were 14 cases of VTE, with an incidence of 0.1% and the only
      specific predictor for postoperative VTE was length of stay (P < .037).
      CONCLUSION: The incidence of VTE following RPS is very low, but it is increased
      in women undergoing concomitant surgeries. Patients undergoing inpatient surgery
      with higher American Society of Anesthesiology Physical Status classifications
      and requiring emergency intervention were at highest risk for VTE.

PMID- 25068558
TI  - Medical education for obstetricians and gynecologists should incorporate
      environmental health.
AB  - Obstetricians-gynecologists can protect the reproductive health of women, men,
      and their offspring from environmental hazards through preconception and prenatal
      counseling and encouraging patients to take actions to reduce environmental
      exposures. Although obstetricians-gynecologists are well positioned to prevent
      hazardous exposures, education on environmental health in medical education is
      limited. The Mid-Atlantic Center for Children's Health and the Environment and
      the Department of Obstetrics and Gynecology of George Washington University
      convened a meeting to begin integration of environmental health topics into
      medical education for obstetricians-gynecologists. Several avenues were
      identified to incorporate environmental health topics into medical education
      including continuing education requirements, inclusion of environmental health
      questions on board certification examinations and the creation of a curriculum on
      environmental health specific to obstetrics-gynecology. 

PMID- 25068559
TI  - Decreased concentration of protease inhibitors: possible contributors to
      allodynia and hyperalgesia in women with vestibulodynia.
AB  - OBJECTIVE: Women with vestibulodynia exhibit increased pain sensitivity to
      contact with the vaginal vestibule as well as with vaginal penetration. The
      mechanism(s) responsible for this effect remains incompletely defined. Based on
      reports of a possible role for proteases in induction of pain, we compared levels
      of proteases and protease inhibitors in vaginal secretions from women with
      vestibulodynia and controls. STUDY DESIGN: Vaginal secretions from 76 women with
      vestibulodynia and from 41 control women were assayed by an enzyme-linked
      immunosorbent assay for the protease inhibitors, secretory leukocyte protease
      inhibitor (SLPI) and human epididymis protein-4 (HE-4), and the proteases,
      kallikrein-5 and cathepsins B and S. Concentrations between subjects and controls
      were compared and levels related to clinical and demographic variables. RESULTS:
      Concentrations of HE-4 and SLPI were markedly reduced in vaginal samples from
      women with vestibulodynia compared with controls (P <= .006). All other compounds
      were similar in both groups. HE-4 (P = .0195) and SLPI (P = .0033) were lower in
      women with secondary, but not primary, vestibulodynia than in controls. Subjects
      who had constant vulvar pain had lower levels of HE-4 and SLPI than did healthy
      control women (P <= .006) or women who experienced vulvar pain only during sexual
      intercourse (P <= .0191). There were no associations between HE-4 or SLPI levels
      and event associated with symptom onset, duration of symptoms, age, number of
      lifetime sexual partners, or age at sex initiation. CONCLUSION: Insufficient
      vaginal protease inhibitor production may contribute to increased pain
      sensitivity in an undefined subset of women with secondary vestibulodynia who
      experience constant vulvar pain.

PMID- 25068560
TI  - Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects: the
      PROMOTE study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of osteopathic
      manipulative treatment (OMT) to reduce low back pain and improve functioning
      during the third trimester in pregnancy and to improve selected outcomes of labor
      and delivery. STUDY DESIGN: Pregnancy research on osteopathic manipulation
      optimizing treatment effects was a randomized, placebo-controlled trial of 400
      women in their third trimester. Women were assigned randomly to usual care only
      (UCO), usual care plus OMT (OMT), or usual care plus placebo ultrasound treatment
      (PUT). The study included 7 treatments over 9 weeks. The OMT protocol included
      specific techniques that were administered by board-certified OMT specialists.
      Outcomes were assessed with the use of self-report measures for pain and back
      related functioning and medical records for delivery outcomes. RESULTS: There
      were 136 women in the OMT group: 131 women in the PUT group and 133 women in the
      UCO group. Characteristics at baseline were similar across groups. Findings
      indicate significant treatment effects for pain and back-related functioning (P <
      .001 for both groups), with outcomes for the OMT group similar to that of the PUT
      group; however, both groups were significantly improved compared with the UCO
      group. For secondary outcome of meconium-stained amniotic fluid, there were no
      differences among the groups. CONCLUSION: OMT was effective for mitigating pain
      and functional deterioration compared with UCO; however, OMT did not differ
      significantly from PUT. This may be attributed to PUT being a more active
      treatment than intended. There was no higher likelihood of conversion to high
      risk status based on treatment group. Therefore, OMT is a safe, effective
      adjunctive modality to improve pain and functioning during the third trimester.

PMID- 25068561
TI  - Gynecology resident laparoscopy training: present and future.
AB  - Simulator education is essential to surgical training and it should be a
      requirement at all training programs across North America. Yet, in a survey of
      North American obstetrics and gynecology program directors (response rate 52%),
      we found that while 73% (n = 98) of programs teach laparoscopic skills, only 59%
      (n = 81) were satisfied with their curriculum. Most programs lacked standard
      setting in the form of theoretical examinations (94%, n = 127) or skills
      assessments (91%, n = 123) prior to residents performing surgery on patients in
      the operating room. Most programs (97%, n = 131) were interested in standardizing
      laparoscopy education by implementing a common curriculum. We present 3 core
      recommendations to ensure that gynecologists across North America are receiving
      adequate training in gynecologic laparoscopic surgery as residents: (1) uniform
      simulator education should be implemented at all training programs across North
      American residency programs; (2) a standardized curriculum should be developed
      using evidence-based techniques; and (3) standardized assessments should take
      place prior to operating room performance and specialty certification. Future
      collaborative research initiatives should focus on establishing the content of a
      standardized laparoscopy curriculum for gynecology residents utilizing a
      consensus method approach. 

PMID- 25068562
TI  - Postinterview communication with residency applicants: a call for clarity!
AB  - The residency match is an increasingly competitive process. Communication from
      medical student applicants to programs varies, and the effect this has on their
      rank status is unclear. We assessed how obstetrics and gynecology program
      directors interpret and act on postinterview communication initiated by
      applicants by conducting an anonymous cross-sectional web-based survey of
      allopathic obstetrics and gynecology program directors. One hundred thirty-seven
      program directors (55%) responded to the survey. Twenty-nine percent would
      consider ranking an applicant more favorably if the applicant expressed interest
      (beyond a routine thank you) or if a faculty mentor personally known to the
      program director stated that the applicant was ranking the program first. Fifty
      two percent indicated that they would rank an applicant more favorably if a
      mentor known to them endorsed the applicant as outstanding. Approximately 30%
      responded that applicants who did not communicate with their program were
      disadvantaged compared with those who did. Approximately 17% stated it was
      desirable to create additional specialty-specific guidelines regarding
      postinterview contact between programs and applications. Based on the wide
      variation in how program directors interpret and act on postinterview
      communication from applicants, residency programs should formulate and
      communicate a clear policy about whether they request and how they respond to
      postinterview communication from applicants and their mentors. This will
      establish a more level playing field and eliminate potential inequities resulting
      from inconsistent communication practices. 

PMID- 25068563
TI  - Lifestyle, distress, and pregnancy outcomes in the Childhood Cancer Survivor
      Study cohort.
AB  - OBJECTIVE: To evaluate associations between prepregnancy lifestyle factors,
      psychologic distress and adverse pregnancy outcomes among female survivors of
      childhood cancer. STUDY DESIGN: We examined pregnancies of 1192 female
      participants from the Childhood Cancer Survivor Study. Generalized linear models,
      adjusted for age at diagnosis, age at pregnancy, parity, and education were used
      to calculate the odds ratio (OR) and confidence interval (CI) for associations
      between prepregnancy inactivity, overweight or obese status, smoking status,
      risky drinking, psychologic distress and pregnancy outcomes. Interactions between
      lifestyle factors, psychologic distress, type of cancer and cancer treatment were
      assessed in multivariable models. RESULTS: The median age of study participants
      at the beginning of pregnancy was 28 years (range, 14-45). Among 1858 reported
      pregnancies, there were 1300 singleton live births (310 were preterm), 21
      stillbirths, 397 miscarriages, and 140 medical abortions. Prepregnancy physical
      inactivity, risky drinking, distress, and depression were not associated with any
      pregnancy outcomes. Compared with those who had never smoked, survivors with >5
      pack-years smoking history had a higher risk for miscarriage among those treated
      with >2.5 Gray (Gy) uterine radiation (OR, 53.9; 95% CI, 2.2-1326.1) than among
      those treated with <=2.5 Gy uterine radiation (OR, 1.9; 95% CI, 1.2-3.0). There
      was a significant interaction between smoking and uterine radiation (Pinteraction
      = .01). CONCLUSION: Although most lifestyle factors and psychologic distress were
      not predictive of adverse pregnancy outcomes, the risk for miscarriage was
      significantly increased among survivors exposed to >2.5 Gy uterine radiation who
      had a history of smoking.

PMID- 25068564
TI  - Defining the residual risk of adverse perinatal outcome in growth-restricted
      fetuses with normal umbilical artery blood flow.
AB  - OBJECTIVE: We sought to determine the cause of adverse perinatal outcome in fetal
      growth restriction (FGR) where umbilical artery (UA) Doppler was normal, as
      identified from the Prospective Observational Trial to Optimize Pediatric Health
      (PORTO). We compared cases of adverse outcome where UA Doppler was normal and
      abnormal. STUDY DESIGN: The PORTO study was a national multicenter study of >1100
      ultrasound-dated singleton pregnancies with an estimated fetal weight <10th
      centile. Each pregnancy underwent intensive ultrasound, including multivessel
      Doppler. UA Doppler was considered abnormal when the pulsatility index was >95th
      centile or end-diastolic flow was absent/reversed. Adverse perinatal outcome was
      defined as a composite of intraventricular hemorrhage, periventricular
      leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis,
      bronchopulmonary dysplasia, sepsis, or death. RESULTS: In all, 57 (5.0%) of the
      1116 fetuses had an adverse perinatal outcome. Nine (1.3%) of 698 fetuses with
      normal UA Doppler had an adverse outcome, compared with 48 (11.5%) of 418 with
      abnormal UA Doppler (P < .0001). There were 2 perinatal deaths in the normal
      group and 6 in the abnormal group (P = .01). The perinatal deaths in the normal
      group were 1 case of pulmonary hypoplasia after prolonged preterm rupture of the
      membranes from 12 weeks' gestation and a case of placental abruption. Gestation
      at delivery was 33 +/- 3 vs 31 +/- 4 weeks (P = .05) and mean birthweight was
      1830 +/- 737 vs 1146 +/- 508 g (P = .001) in the respective groups. Neonatal
      sepsis was the commonest adverse outcome in both groups: 0.1% and 0.4%,
      respectively (P = .01). CONCLUSION: Adverse perinatal outcome is uncommon in FGR
      with normal UA Doppler. The cases we identified were associated with heterogenous
      pathologies. FGR with normal UA blood flow is a largely benign condition.

PMID- 25068565
TI  - A case of ovarian cancer metastases causing a symptomatic paraesophageal hernia.

PMID- 25068566
TI  - Preterm induction of labor: predictors of vaginal delivery and labor curves.
AB  - OBJECTIVE: The purpose of this study was to evaluate the labor curves of patients
      who undergo preterm induction of labor (IOL) and to assess possible predictors of
      vaginal delivery (VD). STUDY DESIGN: Data from the National Institute of Child
      Health and Human Development Consortium on Safe Labor were analyzed. A total of
      6555 women who underwent medically indicated IOL at <37 weeks of gestation were
      included in this analysis. Patients were divided into 4 groups based on
      gestational age (GA): group A, 24-27+6 weeks; B, 28-30+6 weeks; C, 31-33+6 weeks;
      and D, 34-36+6 weeks. Pregnant women with a contraindication to VD, IOL >=37
      weeks of gestation, and without data from cervical examination on admission were
      excluded. Analysis of variance was used to assess differences between GA groups.
      Multiple logistic regression was used to assess predictors of VD. A repeated
      measures analysis was used to determine average labor curves. RESULTS: Rates of
      vaginal live births increased with GA, from 35% (group A) to 76% (group D).
      Parous women (odds ratio, 6.78; 95% confidence interval, 6.38-7.21) and those
      with a favorable cervix at the start of IOL (odds ratio, 2.35; 95% confidence
      interval, 2.23-2.48) were more likely to deliver vaginally. Analysis of labor
      curves in nulliparous women showed shorter duration of labor with increasing GA;
      the active phase of labor was, however, similar across all GAs. CONCLUSION: Most
      women who undergo medically indicated preterm IOL between 24 and 36+6 weeks of
      gestation deliver vaginally. The strongest predictor of VD was parity. Preterm
      IOL had a limited influence on estimated labor curves across GAs.

PMID- 25068568
TI  - Interstate medical licensure: major reform of licensing to encourage medical
      practice in multiple States.

PMID- 25068567
TI  - Psammaplin a improves development and quality of somatic cell nuclear transfer
      mouse embryos.
AB  - Faulty reprogramming of the donor somatic nucleus to a totipotent embryonic state
      by the recipient oocyte is a major obstacle for cloning success. Accordingly,
      treatment of cloned embryos with epigenetic modifiers, such as histone
      deacetylase inhibitors (HDACi), enhances cloning efficiency. The purpose of our
      study was to further explore the potential effect of valproic acid (VPA), used in
      previous studies, and to investigate the effect of psammaplin A (PsA), a novel
      HDACi, on the development and quality of cloned mouse embryos. To this aim,
      cloned embryos were treated with 5, 10, and 20 MUM PsA or 2 and 4 mM VPA for 8-9
      h (before and during activation) or 16 h or 24 h (during and after activation),
      and their in vitro developmental potential and blastocyst quality were evaluated.
      Treatments with 10 MUM PsA and 2 mM VPA for 16 h were selected as the most
      optimal, showing higher blastocyst rates and quality. These treatments had no
      significant effects on the expression of Nanog, Oct4, and Cdx2 or on global
      histone and DNA methylation levels at the blastocyst stage, but both increased
      global levels of histone acetylation at early developmental stages. This was
      correlated with a two-fold (for VPA) and four-fold (for PsA) increase in full
      term development, and a 11.5-fold increase when PsA was combined with the use of
      latrunculin A instead of cytochalasin B. In conclusion, PsA improves mouse
      cloning efficiency to a higher extent than VPA.

PMID- 25068569
TI  - Independent mutations at Arg181 and Arg274 of Vangl proteins that are associated
      with neural tube defects in humans decrease protein stability and impair membrane
      targeting.
AB  - In vertebrates, Vangl proteins play important roles during embryogenesis,
      including establishing planar polarity and coordinating convergent extension
      movements. In mice, homozygosity for mutations in the Vangl1 and Vangl2 genes or
      combined heterozygosity for Vangl1/Vangl2 mutations causes the very severe neural
      tube defect (NTD) craniorachischisis. Recently, a number of patient-specific
      VANGL1 and VANGL2 protein mutations have been identified in familial and sporadic
      cases of mild and severe forms of NTDs. The biochemical nature of pathological
      effects in these mutations remains unknown. Of interest are two arginine
      residues, R181 and R274, that are highly conserved in Vangl protein homologues
      and found to be independently mutated in VANGL1 (R181Q and R274Q) and VANGL2
      (R177H and R270H) in human cases of NTDs. The cellular and biochemical properties
      of R181Q and R274Q were established in transfected MDCK kidney epithelial cells
      and compared to those of wild-type (WT) Vangl1. Compared to that of WT, these
      mutations displayed impaired targeting to the plasma membrane and were instead
      detected in an intracellular endomembrane compartment that was positive for the
      endoplasmic reticulum. R181Q and R274Q showed impaired stability with significant
      reductions in measured half-lives from >20 h for WT protein to 9 and 5 h,
      respectively. These mutations have a cellular and biochemical phenotype that is
      indistinguishable from that of Vangl mutations known to cause craniorachichisis
      in mice (Lp). These results strongly suggest that R181 and R274 play critical
      roles in Vangl protein function and that their mutations cause neural tube
      defects in humans. 

PMID- 25068570
TI  - Design and development of potential tissue engineering scaffolds from
      structurally different longitudinal parts of a bovine-femur.
AB  - The complex architecture of the cortical part of the bovine-femur was examined to
      develop potential tissue engineering (TE) scaffolds. Weight-change and X-ray
      diffraction (XRD) results show that significant phase transformation and
      morphology conversion of the bone occur at 500-750 degrees C and 750-900 degrees
      C, respectively. Another breakthrough finding was achieved by determining a
      sintering condition for the nucleation of hydroxyapatite crystal from bovine bone
      via XRD technique. Scanning electron microscopy results of morphological growth
      suggests that the concentration of polymer fibrils increases (or decreases, in
      case of apatite crystals) from the distal to proximal end of the femur. Energy
      dispersive analysis of X-ray, Fourier transform infrared, micro-computer
      tomography, and mechanical studies of the actual composition also strongly
      support our microscopic results and firmly indicate the functionally graded
      material properties of bovine-femur. Bones sintered at 900 and 1000 degrees C
      show potential properties for soft and hard TE applications, respectively. 

PMID- 25068571
TI  - Successful catheter ablation decreases platelet activation and improves
      endothelial function in patients with atrial fibrillation.
AB  - BACKGROUND: Nonvalvular atrial fibrillation (AF) confers a five-fold increased
      risk of stroke. Whether catheter ablation (CA) subsequently decreases
      prothrombotic risk is unknown. OBJECTIVE: The purpose of this study was to assess
      the long-term effects of CA for AF on prothrombotic risk. METHODS: Fifty-seven
      patients undergoing CA for AF were prospectively studied. Platelet activation
      (CD62P [platelet P-selectin] and PAC-1 [glycoprotein IIb/IIIa] expression) and
      endothelial function (asymmetric dimethylarginine [ADMA] levels) were measured at
      baseline and 6-months postablation. RESULTS: Thirty-seven (65%) patients remained
      in sinus rhythm (SR group) and 20 (35%) sustained AF recurrence (AF recurrence
      group) at 6-months. Patients with AF-recurrence were older, had a higher
      proportion of hypertension and long-standing persistent AF. There were no
      significant differences in CD62P (P = .3), PAC-1 (P = .1) and ADMA (P = .7)
      levels at baseline between the two groups. In the SR group, markers of platelet
      activation decreased significantly at 6-month follow-up compared to baseline; log
      CD62P % 0.79 +/- 0.28 vs 1.03 +/- 0.27 (P <.05) and log PAC-1 % 0.22 +/- 0.58 vs
      0.89 +/- 0.31 (P <.01). This was not significant in the AF-recurrence group (P =
      .8, log CD62P; P = .1, log PAC-1). For endothelial function, ADMA levels
      decreased significantly at 6-months compared to baseline in the SR group (log
      ADMA MUM/L 0.15 +/- 0.02 vs 0.17 +/- 0.04; P <.05), but did not alter
      significantly in the AF-recurrence group (P = .4, log ADMA). CONCLUSION: Catheter
      ablation and successful maintenance of SR leads to a decrease in platelet
      activation and improvement in endothelial function in patients with AF. These
      findings suggest that AF is an important determinant of the prothrombotic state
      and that this may be reduced by successful catheter ablation.

PMID- 25068572
TI  - Correlation of maternal flecainide concentrations and therapeutic effect in fetal
      supraventricular tachycardia.
AB  - BACKGROUND: Transplacental flecainide is an established therapy for fetal
      supraventricular tachycardia (SVT), but there is a paucity of data regarding the
      dose-response relationship. OBJECTIVE: The purpose of this study was to
      investigate the relationship between maternal flecainide concentrations,
      arrhythmia control, and adverse fetal effects in fetal SVT. METHODS: Fetuses with
      SVT treated with transplacental flecainide at our tertiary fetal cardiology unit
      between 1997 and 2012 were retrospectively studied. The maternal trough
      flecainide concentrations throughout treatment were collated, and clinical notes
      were reviewed to ascertain the response to therapy and fetal outcome. RESULTS:
      Thirty-three fetuses were treated at a median (range) gestation of 28 weeks (20
      38 weeks). Median fetal heart rate was 250/min (range 207-316/min). One patient
      was lost to follow-up, and this fetus was excluded from further analysis. In
      total, 25 of 32 fetuses (78%) converted to sinus rhythm. Median time to
      conversion to sinus rhythm was 3 days (range 2-12 days). Median flecainide
      concentration was 460 MUg/L (range 250-866 MUg/L) at conversion to sinus rhythm.
      Flecainide concentrations were not significantly different between responders and
      nonresponders (P = .849). Twelve of 14 hydropic and 13 of 18 nonhydropic fetuses
      converted to sinus rhythm with similar flecainide concentrations (P = .316). No
      fetus achieved cardioversion with a maternal serum flecainide concentration <250
      MUg/L. No fetus died while being treated with flecainide. CONCLUSION: The
      clinical response to flecainide appears good, even in hydropic fetuses. Trough
      maternal flecainide concentrations, once therapeutic, do not predict
      cardioversion in the fetus with SVT. Flecainide therapy appears both safe and
      effective for the fetus when monitored appropriately.

PMID- 25068573
TI  - QRS frequency characteristics help predict response to cardiac resynchronization
      in left bundle branch block less than 150 milliseconds.
AB  - BACKGROUND: Baseline QRS duration (QRSd) >=150 ms is a recognized predictor of
      clinical improvement by cardiac resynchronization therapy (CRT), particularly for
      those with left bundle branch (LBBB). Patients with QRSd <150 ms are considered
      less likely to respond. OBJECTIVE: The purpose of this study was to test our
      theory that left ventricular dyssynchrony, although usually associated with wider
      QRSd, also exhibits lower QRS frequency characteristics and that low-frequency
      content predicts CRT response in LBBB patients. METHODS: We retrospectively
      examined the QRS frequency content of 170 heart failure patients with LBBB and
      QRSd >=120 ms using Fourier transformation. Ninety-four responders to CRT
      (defined as reduction in left ventricular end-systolic volume by >=15% from
      baseline) were compared to 76 nonresponders (<15% reduction). Analysis of 3
      standard ECG leads (I, aVF, and V3) representing the 3 dimensions of
      depolarization was performed, and V3 provided the best predictive value. RESULTS:
      The QRSd of responders (160.3 +/- 17.8 ms) and nonresponders (161.8 +/- 21.1 ms,
      P = .604) were similar. We found that the percentage of total QRS frequency power
      below 10 Hz that exceeded 52% was most predictive of CRT response compared to
      other cutoff values. However, the percentage of patients with total QRS power
      >52% below 10 Hz was especially predictive of response in those with QRSd <150
      ms. In these patients, this power threshold was highly predictive of CRT response
      (positive predictive value 85.7%, negative predictive value 71.4%). CONCLUSION:
      In this group of CRT recipients with LBBB, retrospective analysis of QRS
      frequency content below 10 Hz had greater predictive value for CRT response than
      baseline QRSd, particularly in those with QRSd <150 ms.

PMID- 25068574
TI  - Multicenter study on acute and long-term safety and efficacy of percutaneous left
      atrial appendage closure using an epicardial suture snaring device.
AB  - BACKGROUND: Pericardial suture ligation of the left atrial appendage (LAA) may be
      an alternative to endoluminal devices for stroke prevention in patients with
      atrial fibrillation, but multicenter safety and efficacy data in high-risk
      patients with contraindications to oral anticoagulation are lacking. OBJECTIVE:
      The purpose of this study was to report the outcomes of consecutive cases of
      pericardial suture ligation of the LAA in high-risk patients performed at 4
      centers. METHODS: The cohort included 41 consecutive patients who underwent LAA
      closure with the LARIAT system. Epicardial and transeptal access was obtained,
      and the epicardial snare was advanced over an endo-epicardial magnetic-tipped
      guidewire to close the LAA. Transesophageal echocardiography was used to confirm
      LAA exclusion. RESULTS: Mean age was 75 +/- 10 years, mean CHADS2 score was 3.0
      +/- 1.3, and mean HAS-BLED score was 4.4 +/- 1.4. These patients accumulated 24.6
      person-years of follow-up. Acute LAA closure was achieved in 38 patients (93%).
      Transesophageal echocardiography or computerized tomographic angiography
      performed up to 3.3 +/- 0.8 months after the procedure demonstrated LAA leakage
      in 24% of patients. One patient (2%) had a transient ischemic attack, and 8 (20%)
      developed pericardial effusions requiring pericardiocentesis. Four cases (9%)
      were complicated by perforation of the LAA, with 2 of these patients requiring
      open surgical correction. CONCLUSION: This multicenter experience revealed that
      pericardial suture ligation with the LARIAT system is technically feasible and
      acutely efficacious. However, additional improvements are required to minimize
      the rate of pericardial complications. A randomized study is warranted to
      accurately define the long-term efficacy and safety profile of percutaneous
      epicardial suture ligation.

PMID- 25068575
TI  - Pulmonary vein isolation using "contact force" ablation: the effect on dormant
      conduction and long-term freedom from recurrent atrial fibrillation--a
      prospective study.
AB  - BACKGROUND: Atrial fibrillation (AF) recurrence after pulmonary vein isolation
      (PVI) is associated with PV to left atrium reconduction. Effective lesion
      creation necessitates adequate contact force between the ablation catheter and
      myocardium. OBJECTIVE: The purpose of this study was to study the utility of
      contact force-guided ablation on immediate and long-term outcomes. METHODS:
      Seventy-five patients with highly symptomatic paroxysmal AF underwent wide
      circumferential PVI using an irrigated-tip radiofrequency catheter. In 25
      patients, ablation was guided by real-time contact force measurements (CF group;
      SmartTouch, Biosense Webster). A control group of 50 patients underwent PVI using
      a standard nonforce sensing catheter (standard group; ThermoCool, Biosense
      Webster). After PVI, all patients underwent adenosine testing to unmask dormant
      conduction. Patients were followed up at 3, 6, and 12 months and by
      transtelephonic monitoring as well. RESULTS: Dormant conduction was unmasked and
      subsequently eliminated in 4 PV pairs (8%; 16% of patients) in the CF group and
      35 PV pairs (35%; 52% of patients) in the standard group (P = .0004 per PV pair;
      P = .0029 per patient). The single-procedure, off-antiarrhythmic drug freedom
      from recurrent atrial arrhythmias at 1 year was 88% in the CF group vs 66% in the
      standard group (P = .047). Procedure duration and fluoroscopy time were
      significantly longer in the CF group (P = .0038 and P = .0001, respectively).
      CONCLUSION: The use of real-time contact force guidance results in a significant
      reduction in the prevalence of dormant conduction with improved long-term freedom
      from recurrent arrhythmias. The utility of a contact force-guided approach
      requires evaluation in a long-term prospective randomized study.

PMID- 25068576
TI  - A practical synthesis of indoles via a Pd-catalyzed C-N ring formation.
AB  - A method for the synthesis of N-functionalized C2-/C3-substituted indoles via Pd
      catalyzed C-N bond coupling of halo-aryl enamines is described. The general
      strategy utilizes a variety of amines and beta-keto esters which are elaborated
      into halo-aryl enamines as latent precursors to indoles. The preferred conditions
      comprising the RuPhos precatalyst and RuPhos in the presence of NaOMe in 1,4
      dioxane tolerate a variety of substituents and are scalable for the construction
      of indoles in multigram quantities. 

PMID- 25068577
TI  - Dynamics of non-Brownian fiber suspensions under periodic shear.
AB  - We report experiments studying the dynamics of dense non-Brownian fiber
      suspensions subjected to periodic oscillatory shear. We find that periodic shear
      initially causes fibers to collide and to undergo irreversible diffusion. As time
      progresses, the fibers tend to orient in the vorticity direction while the number
      of collisions decreases. Ultimately, the system goes to one of two steady states:
      an absorbing steady state, where collisions cease and the fibers undergo
      reversible trajectories; an active state, where fibers continue to collide
      causing them to diffuse and undergo irreversible trajectories. Collisions between
      fibers can be characterized by an effective volume fraction Phi with a critical
      volume fraction Phic that separates absorbing from active (diffusing) steady
      states. The effective volume fraction Phi depends on the mean fiber orientation
      and thus decreases in time as fibers progressively orient under periodic shear.
      In the limit that the temporal evolution of Phi is slow compared to the activity
      relaxation time tau, all the data for all strain amplitudes and all
      concentrations can be scaled onto a single master curve with a functional
      dependence well-described by t(-beta/nu)R(e(-t)R), where tR is the rescaled time.
      As Phi -> Phic, tau diverges. Therefore, for experiments in which Phi(t) starts
      above Phic but goes to a steady state below Phic, departures from scaling are
      observed for Phi very near Phic. The critical exponents are measured to be beta =
      0.84 +/- 0.04 and nu = 1.1 +/- 0.1, which is consistent with the Manna
      universality class for directed percolation.

PMID- 25068578
TI  - Inhibition of airway inflammation by the roots of Angelica decursiva and its
      constituent, columbianadin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Angelica decursiva Fr. Et Sav
      (Umbelliferae) have been frequently used in traditional medicine as anti
      inflammatory, antitussive, analgesic agents and expectorant, especially for
      treating cough, asthma, bronchitis and upper respiratory tract infections. To
      establish the scientific rationale for the clinical use of Angelica decursiva and
      to identify new agents for treating inflammatory lung disorders, pharmacological
      evaluation of the roots of Angelica decursiva and the isolated constituents was
      performed. METHODS: In vitro study was carried out using two lung cells, lung
      epithelial cells (A549) and alveolar macrophages (MH-S). The inflammatory markers
      such as IL-6 and nitric oxide (NO) for each cell line were examined. For in vivo
      study, a mouse model of lipopolysaccharide (LPS)-induced acute lung injury was
      used and the effects on lung inflammation were established by measuring the cell
      numbers in bronchoalveolar lavage fluid (BALF) and by histological observation.
      RESULTS: Water and 70% ethanol extracts of the roots of Angelica decursiva showed
      considerable inhibitory activity against LPS-induced lung inflammation in mice
      following oral administration at a dose of 400 mg/kg. Five coumarin derivatives
      including columbianadin, umbelliferone, umbelliferone 6-carboxylic acid,
      nodakenin and nodakenetin were isolated. Among the isolated compounds,
      columbianadin was found to possess strong inhibitory activity against the
      inflammatory response of IL-1beta-treated A549 cells and LPS-treated MH-S cells.
      Columbianadin was found to inhibit NO production by down-regulation of inducible
      NO synthase. Moreover, columbianadin was also proved to possess significant
      inhibitory activity against LPS-induced lung inflammation following oral
      administration at a dose of 20-60 mg/kg. CONCLUSIONS: The roots of Angelica
      decursiva were proved to be effective in the treatment of lung inflammation.
      Columbianadin can be a potential new agent for treating inflammatory lung
      disorders.

PMID- 25068579
TI  - UPLC/MS/MS method for quantification and cytotoxic activity of sesquiterpene
      lactones isolated from Saussurea lappa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea lappa (Asteraceae) roots have been
      reputed for the usage in traditional medicinal systems of India, China and Japan
      for the treatment of various kinds of disorders such as anti-ulcer, anti
      convulsant, anti-cancer, hepatoprotective, anti-arthritic and anti-viral
      activities. MATERIALS AND METHODS: Compounds were isolated using a column
      chromatographic technique. The root extract, fractions and isolated compounds
      were tested for cytotoxicity against A549 (human lung carcinoma) and C-6 (rat
      glioma) cells using the Sulphorhodamine B assay. Chromatographic separations of
      active sesquiterpene lactones were accomplished on BEH-HSS-T3 column at 25
      degrees C. RESULTS: Phytochemical investigation of Saussurea lappa root extract
      resulted in the isolation of isoalantolactone (1), beta-cyclocostunolide (2)
      alpha-cyclocostunolide (3), 4-hydroxy-3,5-dimethoxycinnamyl-9-O-beta-D
      glucopyranoside (4), sucrose (5), and alantolactone (6). Their structures were
      determined by spectroscopic means. Ethanolic extract, chloroform fraction,
      compounds 1, 2, 3 and 6 possessed significant activity against both tested cells.
      The quantification was performed using the transitions of m/z 233/105 for
      isoalantolactone and m/z 233/105 for alantolactone respectively. Costunolide and
      dehydrocostus lactone were also characterised by comparison of MS/MS
      fragmentation pattern. CONCLUSIONS: This is the first study on simultaneous
      quantification of isoalantolactone and alantolactone by the UPLC/MS/MS method in
      Saussurea lappa. Our study against A549 and C-6 cells showed higher cytotoxicity.
      It is suggested that roots of Saussurea lappa might be a potential source of
      anticancer compounds.

PMID- 25068580
TI  - Reproductive toxicology and clastogenic evaluation in mice of a phytotherapeutic
      formulation obtained from Cinchona calisaya Weddel (Rubiaceae) used in Brazilian
      folk medicine as female fertility stimulant.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, a phytotherapeutic preparation
      produced from a standardized tincture of Cinchona calisaya Weddel such that each
      mL of product contains 400ug of quinine, known in Portuguese as Agua Inglesa((r))
      (English water), is indicated by the manufacturer as a tonic, appetite stimulant,
      and digestive. However, this preparation has long been used in folk medicine as a
      female fertility stimulant. Despite its widespread use in folk medicine to
      stimulate female fertility, no study has been undertaken to assess the potential
      teratogenic and genotoxic effects of this phytotherapeutic preparation. The aim
      of the present study was to investigate possible toxic reproductive effects in
      mice caused by exposure to Agua Inglesa((r)), either before mating or during the
      pre- and post-embryo implantation periods. The genotoxic potential was evaluated
      using the micronucleus assay. MATERIAL, METHODS, AND RESULTS: Virgin female mice,
      with at least one estrous cycle evidenced by vaginal cytology, were divided into
      five groups of 15 individuals each (Group I - control, Group II - treated with
      ethanol solution at 16%, Groups III, IV and V treated with phytotherapeutic
      preparation at 1.5mL/kg/day, 3.0mL/kg/day and 4.5mL/kg/day, respectively). After
      the first 28 days of treatment, females were caged individually with adult
      fertile males. Pregnant females continued to receive treatment for seven days
      (preimplantation period). Body weight was recorded weekly during treatment. Signs
      of toxicity (weight loss, food intake, piloerection, apathy, prostration,
      diarrhea, seizures, behavioral changes, and locomotion) were also observed. The
      females were sacrificed on the 15th day of pregnancy, uterine horns were
      evaluated for implantation, and the placental index was recorded. In the
      micronucleus test, 2000 polychromatic erythrocytes (PCE) per animal, obtained
      from bone marrow, were scored. Results The results showed that exposure of the
      females during the pre- and post-implantation periods did not significantly alter
      the reproductive capacity (p<0.05); however, in higher dose (three times human
      dose)reduction of fetal weight was observed . There was no difference between the
      control and phytotherapeutic preparation (p>0.05) in terms of the average number
      of micronucleated polychromatic erythrocytes. CONCLUSIONS: Although folk medicine
      suggests that the Agua Inglesa((r)) preparation is useful as a female fertility
      stimulant, no such effect was confirmed in mice.

PMID- 25068581
TI  - Genetic diversity of Plasmodium vivax over time and space: a community-based
      study in rural Amazonia.
AB  - To examine how community-level genetic diversity of the malaria parasite
      Plasmodium vivax varies across time and space, we investigated the dynamics of
      parasite polymorphisms during the early phases of occupation of a frontier
      settlement in the Amazon Basin of Brazil. Microsatellite characterization of 84
      isolates of P. vivax sampled over 3 years revealed a moderate-to-high genetic
      diversity (mean expected heterozygosity, 0.699), with a large proportion (78.5%)
      of multiple-clone infections (MCI), but also a strong multilocus linkage
      disequilibrium (LD) consistent with rare outcrossing. Little temporal and no
      spatial clustering was observed in the distribution of parasite haplotypes. A
      single microsatellite haplotype was shared by 3 parasites collected during an
      outbreak; all other 81 haplotypes were recovered only once. The lowest parasite
      diversity, with the smallest proportion of MCI and the strongest LD, was observed
      at the time of the outbreak, providing a clear example of epidemic population
      structure in a human pathogen. Population genetic parameters returned to pre
      outbreak values during last 2 years of study, despite the concomitant decline in
      malaria incidence. We suggest that parasite genotyping can be useful for tracking
      the spread of new parasite strains associated with outbreaks in areas approaching
      malaria elimination.

PMID- 25068582
TI  - Atypical signaling and functional desensitization response of MAS receptor to
      peptide ligands.
AB  - MAS is a G protein-coupled receptor (GPCR) implicated in multiple physiological
      processes. Several physiological peptide ligands such as angiotensin-(1-7),
      angiotensin fragments and neuropeptide FF (NPFF) are reported to act on MAS.
      Studies of conventional G protein signaling and receptor desensitization upon
      stimulation of MAS with the peptide ligands are limited so far. Therefore, we
      systematically analyzed G protein signals activated by the peptide ligands. MAS
      selective non-peptide ligands that were previously shown to activate G proteins
      were used as controls for comparison on a common cell based assay platform.
      Activation of MAS by the non-peptide agonist (1) increased intracellular calcium
      and D-myo-inositol-1-phosphate (IP1) levels which are indicative of the
      activation of classical Galphaq-phospholipase C signaling pathways, (2) decreased
      Galphai mediated cAMP levels and (3) stimulated Galpha12-dependent expression of
      luciferase reporter. In all these assays, MAS exhibited strong constitutive
      activity that was inhibited by the non-peptide inverse agonist. Further, in the
      calcium response assay, MAS was resistant to stimulation by a second dose of the
      non-peptide agonist after the first activation has waned suggesting functional
      desensitization. In contrast, activation of MAS by the peptide ligand NPFF
      initiated a rapid rise in intracellular calcium with very weak IP1 accumulation
      which is unlike classical Galphaq-phospholipase C signaling pathway. NPFF only
      weakly stimulated MAS-mediated activation of Galpha12 and Galphai signaling
      pathways. Furthermore, unlike non-peptide agonist-activated MAS, NPFF-activated
      MAS could be readily re-stimulated the second time by the agonists. Functional
      assays with key ligand binding MAS mutants suggest that NPFF and non-peptide
      ligands bind to overlapping regions. Angiotensin-(1-7) and other angiotensin
      fragments weakly potentiated an NPFF-like calcium response at non-physiological
      concentrations (>=100 uM). Overall, our data suggest that peptide ligands induce
      atypical signaling and functional desensitization of MAS. 

PMID- 25068583
TI  - miR-10a regulates proliferation of human cardiomyocyte progenitor cells by
      targeting GATA6.
AB  - microRNAs (miRNAs) play essential roles in cardiogenesis. The altered expression
      of miRNAs can result in cardiac malformations by inducing abnormalities in the
      behavior of cardiac cells. However, the role of miR-10a in the regulation of
      cardiomyocyte progenitor cells (CMPCs) remains undetermined. In the present
      study, we found that up- or down-regulation of miR-10a inhibited or promoted the
      proliferation of human CMPCs, respectively, without affecting their
      differentiation toward cardiomyocytes. miR-10a bound to GATA6 directly and
      reduced GATA6 expression. Over-expression of GATA6 greatly attenuated the miR-10a
      mediated inhibitory effect on the proliferation of human CMPCs. Thus, our results
      indicate that miR-10a could effectively modulate the proliferation of human CMPCs
      by targeting GATA6. The finding provides novel insights into the potency of miR
      10a during heart development. 

PMID- 25068585
TI  - Little Albert's alleged neurological impairment: Watson, Rayner, and historical
      revision.
AB  - In 2012, Fridlund, Beck, Goldie, and Irons (2012) announced that "Little Albert"
      the infant that Watson and Rayner used in their 1920 study of conditioned fear
      (Watson & Rayner, 1920)-was not the healthy child the researchers described him
      to be, but was neurologically impaired almost from birth. Fridlund et al. also
      alleged that Watson had committed serious ethical breaches in regard to this
      research. Our article reexamines the evidentiary bases for these claims and
      arrives at an alternative interpretation of Albert as a normal infant. In order
      to set the stage for our interpretation, we first briefly describe the historical
      context for the Albert study, as well as how the study has been construed and
      revised since 1920. We then discuss the evidentiary issues in some detail,
      focusing on Fridlund et al.'s analysis of the film footage of Albert, and on the
      context within which Watson and Rayner conducted their study. In closing, we
      return to historical matters to speculate about why historiographical disputes
      matter and what the story of neurologically impaired Albert might be telling us
      about the discipline of psychology today.

PMID- 25068587
TI  - Electrochemical behavior of unsupported shaped palladium nanoparticles.
AB  - The potential range in which hydrogen electro-adsorption, electro-absorption, and
      evolution reaction occur is examined in an acidic medium using cyclic-voltammetry
      (CV) and Pd nanoparticles with controlled size and shape distributions. The three
      processes give rise to unique features in CV profiles and are observed in
      distinct potential ranges. This behavior is not observed for bulk Pd materials
      and arises due to the nanoscopic nature of the Pd materials. 

PMID- 25068584
TI  - The use of satellite tags to redefine movement patterns of spiny dogfish (Squalus
      acanthias) along the U.S. east coast: implications for fisheries management.
AB  - Spiny dogfish (Squalus acanthias) are assumed to be a highly migratory species,
      making habitual north-south migrations throughout their northwestern Atlantic
      United States (U.S.) range. Also assumed to be a benthic species, spiny dogfish
      stock structure is estimated through Northeast Fisheries Science Center (NEFSC)
      bottom-trawl surveys. Recent anomalies in population trends, including a recent
      four-fold increase in estimated spawning stock biomass, suggest alternative
      movement patterns could exist for this shark species. To obtain a better
      understanding of the horizontal and vertical movement dynamics of this species,
      Microwave Telemetry pop-up satellite archival X-Tags were attached to forty adult
      spiny dogfish at the northern (Gulf of Maine) and southern (North Carolina)
      extents of their core U.S. geographic range. Reconstructed geolocation tracks
      ranging in lengths from two to 12 months suggest that the seasonal migration
      patterns appear to be local in nature to each respective northern and southern
      deployment site, differing from previously published migration paradigms.
      Differences in distance and direction traveled between seasonal geolocations
      possibly indicate separate migratory patterns between groups. Kernel utilization
      distribution models also suggest strong separate core home ranges. Significant
      differences in seasonal temperature and depths between the two regions further
      substantiate the possibility of separate regional movement patterns between the
      two groups. Vertical utilization also suggests distinct diel patterns and that
      this species may not utilize the benthos as previously thought, potentially
      decreasing availability to benthic gear. 

PMID- 25068588
TI  - Ptychographic inversion via Wigner distribution deconvolution: noise suppression
      and probe design.
AB  - We reconsider the closed form solution of the ptychographic phase problem called
      the Wigner Distribution Deconvolution Method (WDDM), which has remained discarded
      for twenty years. Ptychographic reconstruction is nowadays always undertaken by
      iterative algorithms. WDDM gives rise to a 4 dimensional data cube of all the
      relative phases between points in the diffraction plane. Here we demonstrate a
      novel method to use all this information, instead of just the small subset used
      in the original 'stepping out' procedure developed in the 1990s, thus greatly
      suppressing noise. We further develop a method for designing an improved probe
      (illumination function) to further decrease noise effects during the
      deconvolution division. Combining these two with an iterative procedure for the
      deconvolution, which avoids the usual difficulty of a divide by a small number,
      we show in model calculations that WDDM competes well with the modern
      conventional iterative methods like ePIE (the extended Ptychographical Iterative
      Engine). 

PMID- 25068590
TI  - Mid-level healthcare personnel training: an evaluation of the revised, nationally
      standardized, pre-service curriculum for clinical officers in Mozambique.
AB  - INTRODUCTION: Mozambique suffers from a critical shortage of healthcare workers.
      Mid-level healthcare workers, (Tecnicos de Medicina Geral (TMG)), in Mozambique
      require less money and time to train than physicians. From 2009-2010, the
      Mozambique Ministry of Health (MoH) and the International Training and Education
      Center for Health (I-TECH), University of Washington, Seattle, revised the TMG
      curriculum. To evaluate the effect of the curriculum revision, we used mixed
      methods to determine: 1) if TMGs meet the MoH's basic standards of clinical
      competency; and 2) do scores on measurements of clinical knowledge, physical
      exam, and clinical case scenarios differ by curriculum? METHODS: T-tests of
      differences in means examined differences in continuous score variables between
      curriculum groups. Univariate and multivariate linear regression models assess
      curriculum-related and demographic factors associated with assessment scores on
      each of the three evaluation methods at the p<0.05 level. Qualitative interviews
      and focus groups inform interpretation. RESULTS: We found no significant
      differences in sex, marital status and age between the 112 and 189 TMGs in
      initial and revised curriculum, respectively. Mean scores at graduation of
      initial curriculum TMGs were 56.7%, 63.5%, and 49.1% on the clinical cases,
      knowledge test, and physical exam, respectively. Scores did not differ
      significantly from TMGs in the revised curriculum. Results from linear regression
      models find that training institute was the most significant predictor of TMG
      scores on both the clinical cases and physical exam. CONCLUSION: TMGs trained in
      either curriculum may be inadequately prepared to provide quality care.
      Curriculum changes are a necessary, but insufficient, part of improving TMG
      knowledge and skills overall. A more comprehensive, multi-level approach to
      improving TMG training that includes post-graduation mentoring, strengthening the
      pre-service internship training, and greater resources for training institute
      faculty may result in improvements in TMG capacity and patient care over time.

PMID- 25068589
TI  - Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and
      activate antigen presenting cells.
AB  - The functionalization of polymeric nanoparticles with ligands that target
      specific receptors on immune cells offers the opportunity to tailor adjuvant
      properties by conferring pathogen mimicking attributes to the particles.
      Polyanhydride nanoparticles are promising vaccine adjuvants with desirable
      characteristics such as immunomodulation, sustained antigen release, activation
      of antigen presenting cells (APCs), and stabilization of protein antigens. These
      capabilities can be exploited to design nanovaccines against viral pathogens,
      such as HIV-1, due to the important role of dendritic cells (DCs) and macrophages
      in viral spread. In this work, an optimized process was developed for
      carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride
      nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic
      properties upon release and also enabled sustained antigen release kinetics.
      Particle internalization was observed to be chemistry-dependent with positively
      charged nanoparticles being taken up more efficiently by DCs. Up-regulation of
      the activation makers CD40 and CD206 was demonstrated with carboxymethyl-alpha-d
      mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The
      secretion of the cytokines IL-6 and TNF-alpha was shown to be chemistry-dependent
      upon stimulation with carbohydrate-functionalized nanoparticles. These results
      offer important new insights upon the interactions between carbohydrate
      functionalized nanoparticles and APCs and provide foundational information for
      the rational design of targeted nanovaccines against HIV-1. 

PMID- 25068591
TI  - Reproduction is associated with a tissue-dependent reduction of oxidative stress
      in eusocial female Damaraland mole-rats (Fukomys damarensis).
AB  - Oxidative stress has been implicated as both a physiological cost of reproduction
      and a driving force on an animal's lifespan. Since increased reproductive effort
      is generally linked with a reduction in survival, it has been proposed that
      oxidative stress may influence this relationship. Support for this hypothesis is
      inconsistent, but this may, in part, be due to the type of tissues that have been
      analyzed. In Damaraland mole-rats the sole reproducing female in the colony is
      also the longest lived. Therefore, if oxidative stress does impact the trade-off
      between reproduction and survival in general, this species may possess some form
      of enhanced defense. We assessed this relationship by comparing markers of
      oxidative damage (malondialdehyde, MDA; protein carbonyls, PC) and antioxidants
      (total antioxidant capacity, TAC; superoxide dismutase, SOD) in various tissues
      including plasma, erythrocytes, heart, liver, kidney and skeletal muscle between
      wild-caught reproductive and non-reproductive female Damaraland mole-rats.
      Reproductive females exhibited significantly lower levels of PC across all
      tissues, and lower levels of MDA in heart, kidney and liver relative to non
      reproductive females. Levels of TAC and SOD did not differ significantly
      according to reproductive state. The reduction in oxidative damage in breeding
      females may be attributable to the unusual social structure of this species, as
      similar relationships have been observed between reproductive and non
      reproductive eusocial insects. 

PMID- 25068593
TI  - DABCO-catalyzed ring opening of activated cyclopropanes and recyclization leading
      to gamma-lactams with an all-carbon quaternary center.
AB  - A novel and efficient method for the construction of gamma-lactams with an all
      carbon quaternary center is developed via a DABCO-catalyzed reaction of EWG
      activated cyclopropanecarboxamides and electron-deficient alkenes. The process
      involves sequential ring-opening of activated cyclopropanes, intermolecular
      Michael addition and intramolecular aza-cyclization. 

PMID- 25068592
TI  - Endoscopic biopsy in gastrointestinal neuroendocrine neoplasms: a retrospective
      study.
AB  - BACKGROUND: Gastrointestinal neuroendocrine neoplasms (GI-NENs) are often located
      in the deep mucosa or submucosa, and the efficacy of endoscopic biopsy for
      diagnosis and treatment of GI-NENs is not fully understood. OBJECTIVE: The
      current study analyzed GI-NENs, especially those diagnosed pathologically and
      resected endoscopically, and focused on the biopsy and cold biopsy forceps
      polypectomy (CBP) to analyze their roles in diagnosing and treating GI-NENs.
      METHODS: Clinical data of all GI-NENs were reviewed from January 2006 to March
      2012. Histopathology was used to diagnose GI-NENs, which were confirmed by
      immunohistochemistry. RESULTS: 67.96% GI-NENs were diagnosed pathologically by
      endoscopy. Only 26.21% were diagnosed pathologically by biopsies before
      treatment. The diagnostic rate was significantly higher in polypoid (76.47%) and
      submucosal lesions (68.75%), than in ulcerative lesions (12.00%). However,
      biopsies were only taken in 56.31% patients, including 51.52% of polypoid
      lesions, 35.56% of submucosal lesions and 100.00% of ulcerative lesions.
      Endoscopic resection removed 61.76% of GI-NENs, including six by CBP, 14 by snare
      polypectomy with electrocauterization, 28 by endoscopic mucosal resection (EMR)
      and 15 by endoscopic submucosal dissection (ESD). 51.52% polypoid GI-NENs had
      infiltrated the submucosa under microscopic examination. CBP had a significantly
      higher rate of remnant (33.33%) than snare polypectomy with electrocauterization,
      EMR and ESD (all 0.00%). CONCLUSIONS: Biopsies for all polypoid and submucosal
      lesions will improve pre-operative diagnosis. The high rate of submucosal
      infiltration of polypoid GI-NENs determined that CBP was inadequate in the
      treatment of GI-NENs. Diminutive polypoid GI-NENs that disappeared after CBP had
      a high risk of remnant and should be closely followed up over the long term.

PMID- 25068594
TI  - Interaction between formaldehyde and luminescent MOF [Zn(NH2bdc)(bix)]n in the
      electronic excited state.
AB  - The hydrogen bond between formaldehyde and the luminescent metal-organic
      framework (MOF) [Zn(NH2bdc)(bix)]n was investigated using density functional
      theory and time-dependent density functional theory. The frontier molecular
      orbitals and electronic configuration demonstrate that the origin of the
      luminescence can be attributed to ligand-to-ligand charge transfer. Examination
      of the hydrogen bond behavior in the electronic excited state, with comparison of
      the electronic transition energies, bond distances, binding energy, (1)H-NMR
      chemical shifts, and infrared spectra with those of the ground state, demonstrate
      that the hydrogen bond is stronger when in the electronic excited state.
      Strengthening of the hydrogen bond weakens the radioactive transition of
      [Zn(NH2bdc)(bix)]n, which thus leads to a luminescence decrease or quenching
      phenomenon, meaning that the luminescent MOF [Zn(NH2bdc)(bix)]n may be applied to
      the detection of formaldehyde. 

PMID- 25068595
TI  - PhI(OAc)2-mediated intramolecular oxidative aryl-aldehyde Csp(2)-Csp(2) bond
      formation: metal-free synthesis of acridone derivatives.
AB  - A metal-free protocol for direct aryl-aldehyde Csp(2)-Csp(2) bond formation via a
      PhI(OAc)2-mediated intramolecular cross-dehydrogenative coupling (CDC) of various
      2-(N-arylamino)aldehydes was developed. The novel methodology requires no need of
      preactivation of the aldehyde group, is applicable to a large variety of
      functionalized substrates, and most of all provides a convenient approach to the
      construction of biologically important acridone derivatives. 

PMID- 25068597
TI  - Non-HLA genes in ankylosing spondylitis: what meta-analyses have shown?
AB  - HLA-B27 association with ankylosing spondylitis (AS) is one of the strongest ever
      reported in the literature. However, only a small proportion of 5-8% of HLA-B27
      positive individuals of the general population develops the disease. In recent
      years, polymorphisms of many non-HLA genes were reported to be associated with
      AS. In this review, we summarise the current knowledge of non-HLA genetic factors
      contributing to AS susceptibility based on meta-analyses in order to overcome the
      limitations of individual genetic studies e.g. the small samples' sizes, the
      small samples' origin diversities, and the low statistical power of statistical
      analyses. 

PMID- 25068598
TI  - Bayesian estimates of transition probabilities in seven small lithophytic orchid
      populations: maximizing data availability from many small samples.
AB  - Predicting population dynamics for rare species is of paramount importance in
      order to evaluate the likelihood of extinction and planning conservation
      strategies. However, evaluating and predicting population viability can be
      hindered from a lack of data. Rare species frequently have small populations, so
      estimates of vital rates are often very uncertain due to lack of data. We
      evaluated the vital rates of seven small populations from two watersheds with
      varying light environment of a common epiphytic orchid using Bayesian methods of
      parameter estimation. From the Lefkovitch matrices we predicted the deterministic
      population growth rates, elasticities, stable stage distributions and the
      credible intervals of the statistics. Populations were surveyed on a monthly
      basis between 18-34 months. In some of the populations few or no transitions in
      some of the vital rates were observed throughout the sampling period, however, we
      were able to predict the most likely vital rates using a Bayesian model that
      incorporated the transitions rates from the other populations. Asymptotic
      population growth rate varied among the seven orchid populations. There was
      little difference in population growth rate among watersheds even though it was
      expected because of physical differences as a result of differing canopy cover
      and watershed width. Elasticity analyses of Lepanthes rupestris suggest that
      growth rate is more sensitive to survival followed by growth, shrinking and the
      reproductive rates. The Bayesian approach helped to estimate transition
      probabilities that were uncommon or variable in some populations. Moreover, it
      increased the precision of the parameter estimates as compared to traditional
      approaches. 

PMID- 25068599
TI  - Electronic structure of hemin in solution studied by resonant X-ray emission
      spectroscopy and electronic structure calculations.
AB  - Resonant inelastic X-ray scattering spectra at the iron L-edge from hemin in
      dimethyl sulfoxide liquid solution are reported. Our experiments, which are
      interpreted with the help of electronic structure calculations, support earlier
      assignments of hemin-solvent interactions, including the iron spin state and the
      role of the chloride ligand obtained from a total fluorescence yield study. The
      analysis of the explicit radiative relaxation channels of 2p core-level excited
      iron, explored in the present work, allows for a rather quantitative assignment
      of the orbitals involved in the excitation-deexcitation process of the core
      excited hemin in solution. We specifically distinguish between contributions of
      partially and fully occupied valence orbitals to the broad X-ray emission band.
      In addition, our calculations reveal a detailed picture of the character of these
      orbitals. 

PMID- 25068600
TI  - Bis(6-carboxypurine)-Cu2+: a possibly primitive metal-mediated nucleobase pair.
AB  - A metal-mediated self-pair is described that emulates Watson-Crick base pair
      properties in a DNA double helix. 

PMID- 25068601
TI  - Synthesis, structure, and properties of the electron-poor II-V semiconductor
      ZnAs.
AB  - ZnAs was synthesized at 6 GPa and 1273 K utilizing multianvil high-pressure
      techniques and structurally characterized by single-crystal and powder X-ray
      diffraction (space group Pbca (No. 61), a = 5.6768(2) A, b = 7.2796(2) A, c =
      7.5593(2) A, Z = 8). The compound is isostructural to ZnSb (CdSb type) and
      displays multicenter bonded rhomboid rings Zn2As2, which are connected to each
      other by classical two-center, two-electron bonds. At ambient pressure ZnAs is
      metastable with respect to Zn3As2 and ZnAs2. When heating at a rate of 10 K/min
      decomposition takes place at ~700 K. Diffuse reflectance measurements reveal a
      band gap of 0.9 eV. Electrical resistivity, thermopower, and thermal conductivity
      were measured in the temperature range of 2-400 K and compared to thermoelectric
      ZnSb. The room temperature values of the resistivity and thermopower are ~1 Omega
      cm and +27 MUV/K, respectively. These values are considerably higher and lower,
      respectively, compared to ZnSb. Above 150 K the thermal conductivity attains low
      values, around 2 W/m.K, which is similar to that of ZnSb. The heat capacity of
      ZnAs was measured between 2 and 300 K and partitioned into a Debye and two
      Einstein contributions with temperatures of thetaD = 234 K, thetaE1 = 95 K, and
      thetaE2 = 353 K. Heat capacity and thermal conductivity of ZnSb and ZnAs show
      very similar features, which possibly relates to their common electron-poor
      bonding properties. 

PMID- 25068602
TI  - Filamin A in somatostatin and dopamine receptor regulation in pituitary and the
      role of cAMP/PKA dependent phosphorylation.
AB  - Molecular mechanisms underlying resistance of pituitary tumors to somatostatin
      (SS) and dopamine (DA) analogues treatment are not completely understood.
      Resistance has been associated with defective expression of functional
      somatostatin and dopamine receptors SSTR2, SSTR5, and DRD2, respectively.
      Recently, a role of cytoskeleton protein filamin A (FLNA) in DRD2 and SSTR
      receptors expression and signaling in PRL- and GH-secreting tumors, respectively,
      has been demonstrated, first revealing a link between FLNA expression and
      responsiveness of pituitary tumors to pharmacological therapy. No molecular
      events underlying the reduction of FLNA levels in resistant tumors have been so
      far identified. FLNA can be phosphorylated by PKA on Ser2152, with increased FLNA
      resistance to cleavage by calpain and conformational changes affecting FLNA
      regions involved in SSTR2 and DRD2 binding and signal transduction. In this
      respect, the effect of cAMP/PKA pathway in the regulation of FLNA stability
      and/or function by modulating its phosphorylation status could assume particular
      importance in pituitary, where cAMP cascade plays a crucial role in pituitary
      cell functions and tumorigenesis. This review will discuss the role of FLNA in
      the regulation of the main GPCRs target of pharmacological treatment of pituitary
      tumors, that is, SSTR2 and DRD2, focusing on the effects of cAMP/PKA-mediated
      FLNA phosphorylation on FLNA biological functions. 

PMID- 25068603
TI  - Pupillary effects of high-dose opioid quantified with infrared pupillometry.
AB  - BACKGROUND: The pupillary light reflex is a critical component of the neurologic
      examination, yet whether it is present, depressed, or absent is unknown in
      patients with significant opioid toxicity. Although opioids produce miosis by
      activating the pupillary sphincter muscle, these agents may induce significant
      hypercarbia and hypoxia, causing pupillary constriction to be overcome via
      sympathetic activation. The presence of either "pinpoint pupils" or
      sympathetically mediated pupillary dilation might prevent light reflex
      assessment. This study was designed to determine whether the light reflex remains
      quantifiable during opioid-induced hypercarbia and hypoxia. METHODS: Ten
      volunteers were administered remifentanil with a gradually increasing infusion
      rate and intermittent boluses, until the increasing respiratory depression
      produced an oxyhemoglobin saturation of 85% or less with associated hypercarbia.
      Subjects' heart rate, blood pressure, respiration, and transcutaneous carbon
      dioxide level were continuously recorded. Arterial blood gases and pupillary
      measures were taken before opioid administration, at maximal desaturation, and 15
      min after recovery. RESULTS: The opioid-induced oxygen desaturation (<= 85%) was
      associated with significant hypercarbia and evidence of sympathetic activation.
      During maximal hypoxia and hypercarbia, the pupil displayed parasympathetic
      dominance (2.5 +/- 0.2 mm diameter) with a robust quantifiable light reflex. The
      reflex amplitude was linearly related to pupil diameter. CONCLUSIONS: Opioid
      administration with significant accompanying hypercarbia and hypoxia results in
      pupil diameters of 2 to 3 mm and a reduced but quantifiable pupillary light
      reflex. The authors conclude that the pupillary examination and evaluation of the
      light reflex remain useful for neurologic assessment during opioid toxicity.

PMID- 25068605
TI  - A motivation-based explanatory model of street drinking among young people.
AB  - This social marketing study focuses on street drinking behavior among young
      people. The objective is to divide the market of young people who engage in this
      activity into segments according to their motivations. For the three segments
      identified, a behavior model is created using the beliefs, attitudes, behavior,
      and social belonging of young people who engage in street drinking. The
      methodology used individual questionnaires filled in by a representative sample
      of young people. The results show that the behavior model follows the sequence of
      attitudes-beliefs-behavior and that social belonging influences these three
      variables. Similarly, differences are observed in the behavior model depending on
      the segment individuals belong to. 

PMID- 25068604
TI  - Music listening behavior, health, hearing and otoacoustic emission levels.
AB  - This study examined the relationship between hearing levels, otoacoustic emission
      levels and listening habits related to the use of personal listening devices
      (PLDs) in adults with varying health-related fitness. Duration of PLD use was
      estimated and volume level was directly measured. Biomarkers of health-related
      fitness were co-factored into the analyses. 115 subjects ages 18-84 participated
      in this study. Subjects were divided into two sub-groups; PLD users and non-PLD
      users. Both groups completed audiological and health-related fitness tests. Due
      to the mismatch in the mean age of the PLD user versus the non-PLD user groups,
      age-adjusted statistics were performed to determine factors that contributed to
      hearing levels. Age was the most significant predictor of hearing levels across
      listening and health-related fitness variables. PLD user status did not impact
      hearing measures, yet PLD users who listened less than 8 hours per week with
      intensities of less than 80 dBA were found to have better hearing. Other
      variables found to be associated with hearing levels included: years listening to
      PLD, number of noise environments and use of ear protection. Finally, a healthy
      waist-to-hip ratio was a significant predictor of better hearing, while body mass
      index approached, but did not reach statistical significance. 

PMID- 25068606
TI  - Political power and health inequalities in Vieques, Puerto Rico.
AB  - The relationship between political power and the various pathways to health
      inequalities in Vieques, Puerto Rico, is explored. The U.S. Navy used the island
      for 62 years for bombing and other military exercises. The article focuses on the
      resulting changes to the island's socioeconomic positioning and the health
      inequalities over six decades. Secondary data analysis of census data using a
      revised World Health Organization model is used to examine the relationships of
      political power, labor markets, employment, material deprivation, social and
      family networks, and health inequalities. Findings are interpreted through a
      social justice lens and implications suggest the use of political advocacy for
      social change. 

PMID- 25068607
TI  - Knowledge of causes of VVF and discrimination suffered by patients in Ebonyi
      State, Nigeria: a qualitative study.
AB  - Vesico-vaginal fistula (VVF) is a major public health issue in Nigeria. This
      study focused on VVF patients seeking treatment. Hospital records were used to
      sample 30 respondents. Three focus group discussions were conducted and analyzed
      in themes. Results reveal that most of the respondents did not know what brought
      about their condition, whereas some felt it was a curse from the gods.
      Respondents reported discrimination and stigmatization by relatives. Findings
      suggest the need to have trained social workers working in all fistula centers in
      the country. They will help in the counseling, rehabilitation, and reintegration
      of these women. 

PMID- 25068608
TI  - Private religious practice, spiritual coping, social support, and health status
      among older Korean adult immigrants.
AB  - This study explored the role of spiritual factors and social support on the
      health status of 246 older Korean adult immigrants age 65 years or older.
      Ordinary least squares regression results revealed that private religious
      practice, spiritual coping, and social support were significantly associated with
      improved health status. However, stressors such as the lack of English
      proficiency and transportation, longer residency in the United States, and
      financial problems were significantly associated with lower health status. Social
      workers need to consider providing appropriate spiritual interventions and social
      support programs for older Korean adult immigrants so that they may better handle
      their stressors and health problems. 

PMID- 25068609
TI  - Problematic healthcare insurance: a comparison with successful models.
AB  - This article analyzes the experiences of problematic health insurance models in
      Canada, France, Germany, and Spain, based on news reports, facts, and data. Those
      nations were selected because they represent typical socialist economies with
      nationalized health insurance systems. Major findings are that (a) these health
      insurance systems are not cheap, (b) they sometimes contribute to governments'
      own financial deficits, (c) there are significant restrictions for access to
      private health care, (d) many services are not covered, and (e) the insurance
      plans create conflict as to what treatment options are offered. The author also
      provides a description of the current U.S. health care insurance model and
      compares it with the European socialist model. What comes subsequently is an
      examination of two ideal models of efficient health care insurance: the ones of
      Switzerland and the Netherlands. This analysis ends with a discussion section
      that provides implications for U.S. health care and offers suggestions for future
      research. 

PMID- 25068610
TI  - Assessment of collaboration in U.S. health care delivery: a perspective from
      systems theory.
AB  - This analysis applies the core principles of systems theory to health care
      delivery in the United States. Particularly examined is the role of collaboration
      between health care agencies/organizations in the United States. This includes
      cooperation and teamwork among health professionals (i.e., nurses, technicians,
      physicians, and laboratory staff). By and large, systems theory posits that (a)
      all singular units within a system are interconnected and (b) the whole is more
      than the sum of its parts. This analysis identifies areas within the U.S. public
      health system where it is essential to embody elements of cooperation and
      collaboration, not only to bolster physical and financial support, but also to
      ensure a substantial impact within the community. 

PMID- 25068611
TI  - "Let's Move" campaign: applying the extended parallel process model.
AB  - This article examines Michelle Obama's health campaign, "Let's Move," through the
      lens of the extended parallel process model (EPPM). "Let's Move" aims to reduce
      the childhood obesity epidemic in the United States. Developed by Kim Witte, EPPM
      rests on the premise that people's attitudes can be changed when fear is
      exploited as a factor of persuasion. Fear appeals work best (a) when a person
      feels a concern about the issue or situation, and (b) when he or she believes to
      have the capability of dealing with that issue or situation. Overall, the
      analysis found that "Let's Move" is based on past health campaigns that have been
      successful. An important element of the campaign is the use of fear appeals (as
      it is postulated by EPPM). For example, part of the campaign's strategies is to
      explain the severity of the diseases associated with obesity. By looking at the
      steps of EPPM, readers can also understand the strengths and weaknesses of "Let's
      Move." 

PMID- 25068612
TI  - Illegal private clinics: ideal health services choices among rural-urban migrants
      in China?
AB  - The main purpose of this article is to explore the important issues and the role
      of illegal private clinics in health services access among rural-urban migrants
      in China. The function that illegal private clinics substantially play on the
      health among rural-urban migrants in China is rarely discussed in studies. A
      study on a migrant community in Beijing shows the disadvantaged status of health
      services choices and the constraints for access to health services among
      migrants. It argues that the existence of illegal private clinics provides a
      channel to migrants for medical services in the city and reflects the
      difficulties and high cost of providing medical services to migrants in urban
      public hospitals. Occasionally the illegal private clinics can cause danger to
      the health of migrants. 

PMID- 25068613
TI  - The relationship between restrictive state abortion laws and postpartum
      depression.
AB  - Is there a relationship between restrictive state abortion laws and postpartum
      depression? Do states with restrictive abortion laws have higher rates of
      postpartum depression? If there is a relationship, does it differ by the type of
      restrictive state abortion law? Using the Centers for Disease Control's 2008
      Pregnancy Risk Assessment Monitoring System state survey of the percentage of
      women who gave birth and suffered from postpartum depression, states with and
      without restrictive abortion laws were compared. The empirical results found that
      there were no significant differences in the incidence of postpartum depression
      between states with parental involvement laws, mandatory counseling laws, waiting
      period laws, two-visit laws, and states without these restrictive abortion laws.
      States that prohibit the Medicaid funding of abortions have significantly higher
      rates of postpartum depression than in those states that fund Medicaid abortions.

PMID- 25068614
TI  - Determinants of employment: impact of Medicaid and CHIP among unmarried female
      heads of household with young children.
AB  - This research explores whether participation in Medicaid is a determinant of
      hours of employment among unmarried parenting female heads of households with at
      least one child younger than age 6. The measures include Medicaid participation,
      Children's Health Insurance Program participation, health status, and Medicaid
      generosity. A multilevel regression was conducted using data from the Current
      Population Survey 2011 Annual Social and Economic (ASEC) Supplement. The findings
      indicate that Medicaid participation, health status, and Medicaid generosity all
      have a significant negative effect on labor force participation when measured by
      hours of employment per week. 

PMID- 25068615
TI  - Surface effects on aggregation kinetics of amyloidogenic peptides.
AB  - The presence of surfaces influences the fibril formation kinetics of peptides and
      proteins. We present a systematic study of the aggregation kinetics of
      amyloidogenic peptides caused by different surfaces using molecular simulations
      of model peptides and thioflavin T fluorescence experiments. Increasing the
      monomer-surface attraction affects the nucleation and growth of small oligomers
      in a nonlinear manner: Weakly attractive surfaces lead to retardation; strongly
      attractive surfaces lead to acceleration. Further, the same type of surface
      either accelerates or retards growth, depending on the bulk propensity of the
      peptide to form fibrils: An attractive surface retards fibril formation of
      peptides with a high tendency for fibril formation, while the same surface
      accelerates fibril formation of peptides with a low propensity for fibril
      formation. The surface effect is thus determined by the relative association
      propensity of peptides for the surface compared to bulk and by the surface area
      to protein concentration ratio. This rationalization is in agreement with the
      measured fibrillar growth of alpha-synuclein from Parkinson and amyloid beta
      peptide from Alzheimer disease in the presence of surface area introduced in a
      controlled way in the form of nanoparticles. These findings offer molecular
      insight into amyloid formation kinetics in complex environments and may be used
      to tune fibrillation properties in diverse systems. 

PMID- 25068616
TI  - Improving the anticancer activity of curcumin using nanocurcumin dispersion in
      water.
AB  - Curcumin is a highly potent, nontoxic bioactive agent found in turmeric and is
      known to have significant anticancer properties against different types of cancer
      cells. The major disadvantage associated with the use of curcumin, however, is
      its low systemic bioavailability due to its poor aqueous solubility. The focus of
      the present study was to generate nanoparticles of curcumin with improved aqueous
      phase solubility, and to investigate their efficacy in treating cancer cells.
      Curcumin nanoparticles having particle size in the range 2-40 nm and aqueous
      solubility of up to a maximum of 3 mg/mL were prepared. Evaluation of anticancer
      properties of curcumin nanodispersion was carried out in 3 different cancer cell
      lines: lung (A549), liver (HepG2), and skin (A431). The results demonstrated that
      under aqueous conditions curcumin nanoparticles exhibited similar or a much
      stronger antiproliferative effect on the cancer cells compared to normal curcumin
      in DMSO. Our results lead way toward unharnessed potential of curcumin in the
      form of its nanoparticles as an adjuvant therapy for clinical application in
      treating various cancers.

PMID- 25068617
TI  - A redesigned Escherichia coli triosephosphate isomerase restores growth
      properties in a bacterial strain useful for Immobilized Metal Affinity
      Chromatography (IMAC).
AB  - The bacterium Escherichia coli is one of the most commonly used organisms in
      biotechnology for recombinant protein production and high-throughput development
      of biopharmaceuticals. The focus of this article is the utilization of proteome
      based data to design an E. coli expression strain that is improved for initial
      protein capture via Immobilized Metal Affinity Chromatography (IMAC). Proteome
      data was specifically applied to guide the modification of a known IMAC binding
      protein, triosephosphate isomerase (tpiA gene product), and the use of site
      directed mutagenesis eliminated binding properties. The designer tpiA gene, when
      reintroduced into an E. coli strain deficient in this enzyme activity, produced a
      functional protein lacking in surface exposed histidine and was able to restore
      glycolytic function. 

PMID- 25068618
TI  - Assessment of the CO2 fixation capacity of Anabaena sp. ATCC 33047 outdoor
      cultures in vertical flat-panel reactors.
AB  - The extent of biological CO2 fixation was evaluated for outdoor cultures of the
      cyanobacterium Anabaena sp. ATCC 33047. Culture conditions were optimized indoors
      in bubble-column photochemostats operating in continuous mode, subjected to
      irradiance cycles mimicking the light regime outdoors. Highest values achieved
      for CO2 fixation rate and biomass productivity were 1 and 0.6 g L(-1) day(-1),
      respectively. The comparison among different reactors operating simultaneously -
      open pond, horizontal tubular reactor and vertical flat-panel - allowed to assess
      their relative efficiency for the outdoor development of Anabaena cultures.
      Despite the higher volumetric CO2 fixation capacity (and biomass productivity)
      exhibited by the tubular photobioreactor, yield of the flat-panel reactor was 50%
      higher than that of the tubular option on a per area basis, reaching values over
      35 g CO2 fixed m(-2) d(-1). The flat-panel reactor actually represents a most
      suitable system for CO2 capture coupled to the generation of valuable biomass by
      Anabaena cultures.

PMID- 25068619
TI  - Particle-water interactions of platinum-based anticancer drugs in river water and
      estuarine water.
AB  - The cytotoxic, platinum-based anticancer drugs, cisplatin, carboplatin and
      oxaliplatin, enter the aquatic environment largely in municipal wastes via
      excretion from outpatients undergoing chemotherapy. The environmental behaviour,
      effects and fate of these drugs are, however, unknown. In this study, the
      adsorption of the drugs to untreated and chemically modified (oxide-free and
      organic-free) sediment was examined in both river water and low salinity (S=3.2)
      estuarine water in order to determine the nature and extent of their interactions
      with suspended particles. In all cases, adsorption isotherms were linear, and the
      slopes of the relationships, or distribution coefficients (KDs), ranged from
      about 10(2) to 10(3) ml g(-1). Overall, adsorption decreased in the order:
      cisplatin>carboplatin>oxaliplatin; in river water and: cisplatin>carboplatin,
      oxaliplatin; in estuarine water. There was no clear dependence of adsorption on
      sediment treatment but, for all sediment types, both cisplatin and carboplatin
      adsorption was greater in river water than in estuarine water. Qualitatively,
      these observations are consistent with the rates of formation of reactive,
      aquated degradation products and the dependencies of these rates on aqueous
      chloride concentration. We predict that during transport through an estuarine
      turbidity maximum (of suspended sediment concentration=1 g L(-1)), up to about
      45% of cisplatin and 35% of carboplatin are filtered out from the aqueous phase
      but that no more than 7% of oxaliplatin is retained.

PMID- 25068620
TI  - Environmental risks for nontuberculous mycobacteria. Individual exposures and
      climatic factors in the cystic fibrosis population.
AB  - RATIONALE: Persons with cystic fibrosis are at high risk of pulmonary
      nontuberculous mycobacterial infection, with a national prevalence estimated at
      13%. The risk of nontuberculous mycobacteria associated with specific
      environmental exposures, and the correlation with climatic conditions in this
      population has not been described. OBJECTIVES: To describe the association of
      pulmonary nontuberculous mycobacteria with individual exposures to water and soil
      aerosols, and the population associations of these infections with climatic
      factors. METHODS: We conducted a nested case-control study within a cohort study
      of pulmonary nontuberculous mycobacteria prevalence at 21 geographically diverse
      national cystic fibrosis centers. Incident nontuberculous mycobacterial infection
      cases (at least one prior negative culture followed by one positive culture) were
      age- and sex-matched to culture-negative controls. Exposures to water and soil
      were assessed by administering a standardized questionnaire. Cohort prevalence at
      each of the 21 centers was correlated with climatic conditions in the same area
      through linear regression modeling. MEASUREMENTS AND MAIN RESULTS: Overall, 48
      cases and 85 control subjects were enrolled. Indoor swimming was associated with
      incident infection (adjusted odds ratio, 5.9, 95% confidence interval, 1.3-26.1),
      although only nine cases (19%) and five control subjects (6%) reported indoor
      swimming in the 4 months prior to infection. Exposure to showering and municipal
      water supply was common among both cases and control subjects: 77% of cases and
      76% of control subjects reported showering at least daily. In linear regression,
      average annual atmospheric water vapor content was significantly predictive of
      center prevalence (P = 0.0019), with R(2) = 0.40. CONCLUSIONS: Atmospheric
      conditions explain more of the variation in disease prevalence than individual
      behaviors. The risk of specific exposures may vary by geographic region due to
      differences in conditions favoring mycobacterial growth and survival. However,
      because exposure to these organisms is ubiquitous and behaviors are similar among
      persons with and without pulmonary nontuberculous mycobacteria, genetic
      susceptibility beyond cystic fibrosis is likely to be important for disease
      development. Common individual risk factors in high-risk populations remain to be
      identified.

PMID- 25068621
TI  - QKI deficiency promotes FoxO1 mediated nitrosative stress and endoplasmic
      reticulum stress contributing to increased vulnerability to ischemic injury in
      diabetic heart.
AB  - Hearts of diabetic individuals are susceptible to ischemia/reperfusion (I/R)
      injury. The RNA-binding protein Quaking (QKI) is known to link intracellular
      signaling to cellular survival and QKI dysregulation may contribute to human
      diseases. However, the function of QKI in diabetic hearts remains unknown. The
      current study attempted to identify new molecular mechanisms that potentially
      contribute to the susceptibility to ischemic injury in diabetic myocardium.
      Diabetic ob/ob mice or wild-type C57BL/6J mice were subjected to in vivo
      myocardial I/R. Myocardial infarct size and apoptosis, QKI5 and FoxO1 expression,
      nitrosative stress (NS) and ER stress were compared. Knockdown of FoxO1 was
      obtained by intramyocardial injection of FoxO1 specific small interfering RNA
      (siRNA, 20MUg), and upregulation of QKI5 was acquired by injecting adenovirus
      encoding-QKI5. Obvious NS stress was observed in the myocardium of ob/ob mice
      represented by elevated iNOS expression, total NO content and nitrotyrosine
      content. Administration of 1400W or M40401 partly reduced the caspase-3 activity
      in ob/ob myocardium encountering I/R (P<0.05). Higher ER stress was also observed
      represented by increased p-PERK, p-eIF2alpha and expression of CHOP in ob/ob
      myocardium. ER stress inhibitor did not affect the excessive NS stress, but
      partially reduced I/R-induced caspase-3 activity in ob/ob hearts (P<0.05). FoxO1
      was overactivated in ob/ob myocardium, and knockdown of FoxO1 attenuated both
      levels of NS stress and ER stress (P<0.05). Furthermore, QKI5 expression was
      deficient in ob/ob myocardium. Upregulation of QKI5 diminished FoxO1 expression
      together with NS and ER stress in ob/ob myocardium, further reducing MI/R injury.
      Finally, QKI5 overexpression destabilized FoxO1 mRNA in cardiomyocytes. These
      results suggested that QKI5 deficiency contributed to the overactivation of FoxO1
      in ob/ob animals and subsequently magnified nitrosative stress and ER stress,
      which enhances the ischemic intolerance of diabetic hearts. 

PMID- 25068622
TI  - Competitive dynamics on complex networks.
AB  - We consider a dynamical network model in which two competitors have fixed and
      different states, and each normal agent adjusts its state according to a
      distributed consensus protocol. The state of each normal agent converges to a
      steady value which is a convex combination of the competitors' states, and is
      independent of the initial states of agents. This implies that the competition
      result is fully determined by the network structure and positions of competitors
      in the network. We compute an Influence Matrix (IM) in which each element
      characterizing the influence of an agent on another agent in the network. We use
      the IM to predict the bias of each normal agent and thus predict which competitor
      will win. Furthermore, we compare the IM criterion with seven node centrality
      measures to predict the winner. We find that the competitor with higher Katz
      Centrality in an undirected network or higher PageRank in a directed network is
      most likely to be the winner. These findings may shed new light on the role of
      network structure in competition and to what extent could competitors adjust
      network structure so as to win the competition. 

PMID- 25068623
TI  - Authors' response to Brouwer (DOI: 10.1089/jwh.2014.4881).

PMID- 25068624
TI  - Insights into aging: pain changes everything.

PMID- 25068629
TI  - Conductive water/alcohol-soluble neutral fullerene derivative as an interfacial
      layer for inverted polymer solar cells with high efficiency.
AB  - Dipole induced vacuum level shift has been demonstrated to be responsible for the
      enhanced efficiency in polymer solar cells (PSCs).The modified energy level
      alignment could reduce the energy barrier and facilitate charge transport,
      thereby increasing the efficiency of PSCs. Herein, we report a new mechanism
      toward enhanced efficiency by using a nondipolar water/alcohol-soluble neutral
      fullerene derivative to reengineer the surface of the zinc oxide (ZnO) electron
      extraction layer (EEL) in inverted PSCs. Because of the neutral property (ion
      free) of the fullerene derivatives, no dipole moment was introduced at the
      EEL/active layer interface. A negligible change in open-circuit voltage was
      observed from inverted PSCs with the neutral fullerene derivative layer. The
      neutral fullerene derivative layer greatly increased the surface electronic
      conductivity of the ZnO EEL, suppressed surface charge recombination, and
      increased the short-circuit current density and fill factor. An overall power
      conversion efficiency increase of more than 30% from inverted PSCs was obtained.
      These results demonstrate that the surface electronic conductivity of the EEL
      plays an important role in high performance inverted PSCs. 

PMID- 25068628
TI  - Formation of multigradient porous surfaces for selective bacterial entrapment.
AB  - Herein we describe the preparation of multigradient porous platforms by using the
      breath figures approach. In a single and straightforward step, we prepared porous
      surfaces in which three different parameters vary gradually from the edge of the
      sample to the center in a radial manner. Thus, we evidenced the gradual variation
      of the pore size and the shape of the pores that can be varied, depending on the
      sample concentration, but also depending on their radial position within the same
      sample. In addition, we succeeded in the control over the chemical composition
      inside and outside the pores as well as the variation of the concentration of
      block copolymer inside the pores as a function of their radial position.
      Moreover, the chemical composition and the variable cavity size of porous
      surfaces have been evaluated to analyze the influence of these variables on the
      selective bacterial immobilization. To the best of our knowledge this is the
      first example in which, by using a simple one-step strategy, a multigradient
      surface can be obtained. These initial results can be the base to construct
      platforms for selective immobilization and isolation of bacteria. 

PMID- 25068631
TI  - Characterization of amniotic stem cells.
AB  - The amnion membrane is developed from embryo-derived cells, and amniotic cells
      have been shown to exhibit multidifferentiation potential. These cells represent
      a desirable source for stem cells for a variety of reasons. However, to date very
      few molecular analyses of amnion-derived cells have been reported, and efficient
      markers for isolating the stem cells remain unclear. This paper assesses the
      characterization of amnion-derived cells as stem cells by examining stemness
      marker expressions for amnion-derived epithelial cells and mesenchymal cells by
      flow cytometry, immunocytochemistry, and quantitative PCR. Flow cytometry
      revealed that amnion epithelial cells expressed CD133, CD 271, and TRA-1-60,
      whereas mecenchymal cells expressed CD44, CD73, CD90, and CD105.
      Immunohistochemistry showed that both cells expressed the stemness markers
      Oct3/4, Sox2, Klf4, and SSEA4. Stemness genes' expression in amnion epithelial
      cells, mesenchymal cells, fibroblast, bone marrow-derived mesenchymal stem cells
      (MSCs), and induced pluripotent stem cells (iPSCs) was compared by quantitative
      reverse-transcription polymerase chain reaction (RT-PCR). Amnion-derived
      epithelial cells and mesenchymal cells expressed Oct3/4, Nanog, and Klf4 more
      than bone marrow-derived MSCs. The sorted TRA1-60-positive cells expressed
      Oct3/4, Nanog, and Klf4 more than unsorted cells or TRA1-60-negative cells. TRA1
      60 can be a marker for isolating amnion epithelial stem cells.

PMID- 25068630
TI  - Murine embryonic fibroblast cell lines differentiate into three mesenchymal
      lineages to different extents: new models to investigate differentiation
      processes.
AB  - Various diseases, injuries, and congenital abnormalities may result in
      degeneration and loss of organs and tissues. Recently, tissue engineering has
      offered new treatment options for these common, severe, and costly problems in
      human health care. Its application is often based on the usage of differentiated
      stem cells. However, despite intensive research and growing knowledge, many
      questions remain unresolved in the process of cell differentiation. The aim of
      this study was to find standardized cell models for analyzing molecular
      mechanisms of cell differentiation. We investigated the multipotency of three
      standardized murine embryonic fibroblast cell cultures using histological
      staining, western blotting, and quantitative real-time reverse transcription
      polymerase chain reaction (qRT-PCR). Our results demonstrated that NIH-3T3 and
      mouse embryonic fibroblast (MEF) cells were able to differentiate into
      adipogenic, chondrogenic, and osteogenic lineages expressing typical
      differentiation markers. Interestingly, Flp-In-3T3 cells did not differentiate
      into any of the three mesenchymal lineages, although this cell line is
      genetically closely related to NIH-3T3. The results were confirmed by
      histological staining. Flp-In-3T3, NIH-3T3, and MEF cells have usually been used
      for DNA transfections, recombinant protein expression, and as "feeder cells."
      Unlike mesenchymal stem cells (MSCs) and mesenchymal progenitor cells (MPCs),
      they are easy to obtain and to expand and are less prone to change their
      structure and morphology, even at higher passages. Our results suggest that Flp
      In-3T3, MEF, and NIH-3T3 cells are highly suitable to be used as models to
      analyze molecular mechanisms of cell differentiation.

PMID- 25068632
TI  - The global financial crisis, health and health care.

PMID- 25068633
TI  - Protein assembly mediated by sulfonatocalix[4]arene.
AB  - A crystal structure of lysozyme in complex with p-sulfonato-calix[4]arene (sclx4)
      reveals a linear assembly of protein tetramers glued together by protein
      calixarene interactions. One interaction involves encapsulation of the highly
      exposed C-terminal Arg128. The other involves an intricate protein-bound complex
      of sclx4, Mg(2+) and a fragment of polyethylene glycol. 

PMID- 25068634
TI  - Self-organization of functional materials in confinement.
AB  - This Account aims to describe our experience in the use of patterning techniques
      for addressing the self-organization processes of materials into spatially
      confined regions on technologically relevant surfaces. Functional properties of
      materials depend on their chemical structure, their assembly, and spatial
      distribution at the solid state; the combination of these factors determines
      their properties and their technological applications. In fact, by controlling
      the assembly processes and the spatial distribution of the resulting structures,
      functional materials can be guided to technological and specific applications. We
      considered the principal self-organizing processes, such as crystallization,
      dewetting and phase segregation. Usually, these phenomena produce defective
      molecular films, compromising their use in many technological applications. This
      issue can be overcome by using patterning techniques, which induce molecules to
      self-organize into well-defined patterned structures, by means of spatial
      confinement. In particular, we focus our attention on the confinement effect
      achieved by stamp-assisted deposition for controlling size, density, and
      positions of material assemblies, giving them new chemical/physical
      functionalities. We review the methods and principles of the stamp-assisted
      spatial confinement and we discuss how they can be advantageously exploited to
      control crystalline order/orientation, dewetting phenomena, and spontaneous phase
      segregation. Moreover, we highlight how physical/chemical properties of soluble
      functional materials can be driven in constructive ways, by integrating them into
      operating technological devices.

PMID- 25068635
TI  - Alkene hydrofunctionalization using hydroxamic acids: a radical-mediated approach
      to alkene hydration.
AB  - A radical-mediated approach to alkene hydration is described. The present
      strategy capitalizes on the unique radical reactivity of hydroxamic acids, which
      are capable of functioning as both synthetically useful oxygen-centered radical
      species and suitable hydrogen atom-based donors. This reaction manifold has been
      applied to both alkene hydrations and tandem alkene-alkene carbocyclization
      processes. 

PMID- 25068636
TI  - Detection of intermediates in the oxidative half-reaction of the FAD-dependent
      thymidylate synthase from Thermotoga maritima: carbon transfer without covalent
      pyrimidine activation.
AB  - Thymidylate, a vital DNA precursor, is synthesized by thymidylate synthases
      (TSs). A second class of TSs, encoded by the thyX gene, is found in bacteria and
      a few other microbes and is especially widespread in anaerobes. TS encoded by
      thyX requires a flavin adenine dinucleotide prosthetic group for activity. In the
      oxidative half-reaction, the reduced flavin is oxidized by 2'-deoxyuridine 5'
      monophosphate (dUMP) and (6R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate (CH2THF),
      synthesizing 2'-deoxythymidine 5'-monophosphate (dTMP). dTMP synthesis is a
      complex process, requiring the enzyme to promote carbon transfer, probably by
      increasing the nucleophilicity of dUMP and the electrophilicity of CH2THF, and
      reduction of the transferred carbon. The mechanism of the oxidative half-reaction
      was investigated by transient kinetics. Two intermediates were detected, the
      first by a change in the flavin absorbance spectrum in stopped-flow experiments
      and the second by the transient disappearance of deoxynucleotide in acid
      quenching experiments. The effects of substrate analogues and the behavior of
      mutated enzymes on these reactions lead to the conclusion that activation of dUMP
      does not occur through a Michael-like addition, the mechanism for the activation
      analogous with that of the flavin-independent TS. Rather, we propose that the
      nucleophilicity of dUMP is enhanced by electrostatic polarization upon binding to
      the active site. This conclusion rationalizes many of our observations, for
      instance, the markedly slower reactions when two arginine residues that hydrogen
      bond with the uracil moiety of dUMP were mutated to alanine. The activation of
      dUMP by polarization is consistent with the majority of the published data on
      ThyX and provides a testable mechanistic hypothesis.

PMID- 25068638
TI  - Cupping reversal in pediatric glaucoma--evaluation of the retinal nerve fiber
      layer and visual field.
AB  - PURPOSE: To identify optic nerve head (ONH) cupping reversal and associated
      optical coherence tomography (OCT) and Humphrey visual field changes in pediatric
      glaucoma. DESIGN: Retrospective observational case series. METHODS: Sequential
      surgical cases of juvenile open-angle glaucoma (OAG) or primary congenital
      glaucoma (PCG) with sustained postoperative intraocular pressure (IOP) reduction.
      Group 1 had preoperative and postoperative ONH photographs and OCT; Group 2 had
      preoperative clinical ONH assessment and postoperative imaging. Cupping
      evaluation was confirmed by masked glaucoma and neuro-ophthalmology specialists.
      RESULTS: Of 80 cases, 9 eyes (9 children) met criteria for Group 1; 24 eyes (19
      children) met criteria for Group 2. Group 1: Five of 9 eyes (56%) demonstrated
      cupping reversal, with preoperative vs postoperative mean IOP 34.2 +/- 6.6 mm Hg
      vs 10.6 +/- 4.1 mm Hg (P < .00001) and mean average retinal nerve fiber layer
      (RNFL) 71.0 +/- 30 MUm vs 62.8 +/- 24 MUm (P = .4), respectively. RNFL was stable
      in 4 of 5 eyes (all juvenile OAG), but thinned (Delta = -41 MUm) in 1 eye with
      PCG. Humphrey visual fields (reliable in 2 of 3 eyes) showed no significant
      change. Group 2: Fourteen of 24 PCG eyes (58%) demonstrated cupping reversal,
      with preoperative vs postoperative mean IOP 36.1 +/- 8.9 mm Hg vs 13.3 +/- 2.1 mm
      Hg (P < .00001). Two eyes had thin RNFL postoperatively despite healthy-appearing
      ONH. Postoperative RNFL showed statistically significant linear correlation with
      preoperative (but not postoperative) cup-to-disc ratio. Limitations include small
      numbers, few reliable Humphrey visual fields, and absent preoperative imaging
      (Group 2). CONCLUSION: Some eyes with IOP reduction and ONH cupping reversal show
      continued RNFL thinning postoperatively. The preoperative ONH cup-to-disc ratio
      predicted the postoperative RNFL better than the postoperative "reversed and
      smaller" cup-to-disc ratio. Cupping reversal in pediatric glaucoma may not
      predict improved ONH health and deserves further study.

PMID- 25068637
TI  - Intravitreal aflibercept for macular edema secondary to central retinal vein
      occlusion: 18-month results of the phase 3 GALILEO study.
AB  - PURPOSE: To evaluate intravitreal aflibercept for treatment of macular edema
      secondary to central retinal vein occlusion (CRVO). DESIGN: Randomized, double
      masked, phase 3 study. METHODS: A total of 177 patients with macular edema
      secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n =
      106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients
      were monitored every 4 weeks; the former group received intravitreal aflibercept
      as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients
      were monitored every 8 weeks, and both groups received intravitreal aflibercept
      PRN. The primary endpoint (proportion of patients who gained >=15 letters) was at
      week 24. This study reports exploratory outcomes at week 76. RESULTS: The
      proportion of patients who gained >=15 letters in the intravitreal aflibercept
      and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week
      24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last
      observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last
      observation carried forward; P < .001). Mean MUm change from baseline central
      retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3
      at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76
      weeks, the most common ocular serious adverse event in the intravitreal
      aflibercept group was macular edema (3.8%). CONCLUSIONS: The visual and anatomic
      improvements seen after fixed, monthly dosing at week 24 were largely maintained
      when treatment intervals were extended. Patients with macular edema following
      CRVO benefited from early treatment with intravitreal aflibercept.

PMID- 25068639
TI  - Intra- and inter-visit reproducibility of ganglion cell-inner plexiform layer
      measurements using handheld optical coherence tomography in children with optic
      pathway gliomas.
AB  - PURPOSE: To determine the intra- and inter-visit reproducibility of ganglion cell
      inner plexiform layer thickness measures using handheld optical coherence
      tomography (OCT) in sedated children with optic pathway gliomas and/or
      neurofibromatosis type 1 (NF1). DESIGN: Prospective longitudinal cohort study.
      METHODS: Children with sporadic optic pathway gliomas and/or NF1 who had >=2
      volumes acquired over the macula using handheld OCT during sedation for
      clinically indicated magnetic resonance imaging were eligible for the intra-visit
      cohort. Children with repeat handheld OCT imaging within 6 months were eligible
      for the inter-visit cohort. Total retinal thickness and ganglion cell-inner
      plexiform layer thickness were measured using custom-designed automated
      segmentation software. Reproducibility was compared across average and anatomic
      quadrant by calculating the coefficient of variation (CV) and intraclass
      correlation coefficient (ICC). RESULTS: Forty-two subjects (median age 5.4 years,
      range 0.8-12.7 years) contributed 45 eyes to the intra-visit cohort. Thirty-one
      subject eyes had normal vision and 14 had abnormal vision (decreased visual
      acuity and/or visual field). Average and quadrant ganglion cell-inner plexiform
      layer measures demonstrated CVs <=4.5% with excellent ICCs (>0.935). The superior
      quadrant CV differed between subjects with (4.4%) and without (2.1%) vision loss
      (P < .05). Twenty-five subject eyes were eligible for the inter-visit cohort,
      demonstrating CVs from 1.6% to 5.2%. Inter-visit ICCs were excellent (0.955
      0.995). DISCUSSION: Handheld OCT imaging in sedated children with optic pathway
      gliomas produces highly reproducible measures of ganglion cell-inner plexiform
      layer thickness.

PMID- 25068640
TI  - Fundus autofluorescence patterns in Best vitelliform macular dystrophy.
AB  - PURPOSE: To provide a systematic classification of fundus autofluorescence (FAF)
      patterns in patients affected by Best vitelliform macular dystrophy. DESIGN:
      Cross-sectional prospective study. METHODS: Patients affected by Best vitelliform
      macular dystrophy at different stages of the disease were prospectively enrolled
      from January 2012 to July 2013. Eighty eyes of 40 patients were included in the
      study. All patients underwent a complete ophthalmologic examination, including
      genetic characterization, short-wavelength FAF, and near-infrared FAF. Main
      outcome measures were the recognition of the FAF patterns in the different stages
      and the identification of a relationship between FAF patterns and best-corrected
      visual acuity (BCVA). RESULTS: Six FAF patterns for both short-wavelength and
      near-infrared FAF were identified, including normal, hyper-autofluorescent, hypo
      autofluorescent, patchy, multifocal, and spoke-like patterns. Applying Gass's
      classification for defining consecutive stages of Best vitelliform macular
      dystrophy (namely vitelliform, pseudohypopyon, vitelliruptive, atrophic, and
      cicatricial) identified no pattern as stage-specific. Patchy patterns had the
      highest prevalence. A statistically significant difference (Kruskal-Wallis ANOVA)
      was found among hyper-autofluorescent, patchy, and hypo-autofluorescent patterns,
      both in short-wavelength (P = .001) and near-infrared FAF (P = .001). Hyper
      autofluorescent and hypo-autofluorescent patterns were associated with better and
      worse BCVA, respectively. CONCLUSIONS: Six main patterns on both short-wavelength
      and near-infrared FAF were identified in Best vitelliform macular dystrophy. No
      FAF pattern can be considered stage-specific. Although a difference in the BCVA
      among the FAF patterns was registered, only a longitudinal study designed to
      evaluate the clinical and FAF modifications over the follow-up will help clarify
      the prognostic implications of each FAF pattern.

PMID- 25068641
TI  - Glaucomatous retinal nerve fiber layer thickness loss is associated with slower
      reaction times under a divided attention task.
AB  - PURPOSE: To examine the relationship between glaucomatous structural damage and
      ability to divide attention during simulated driving. DESIGN: Cross-sectional
      observational study. METHODS:  SETTING: Hamilton Glaucoma Center, University of
      California San Diego. PATIENT POPULATION: Total of 158 subjects from the
      Diagnostic Innovations in Glaucoma Study, including 82 with glaucoma and 76
      similarly aged controls. OBSERVATION PROCEDURE: Ability to divide attention was
      investigated by measuring reaction times to peripheral stimuli (at low, medium,
      or high contrast) while concomitantly performing a central driving task (car
      following or curve negotiation). All subjects had standard automated perimetry
      (SAP) and optical coherence tomography was used to measure retinal nerve fiber
      layer (RNFL) thickness. Cognitive ability was assessed using the Montreal
      Cognitive Assessment and subjects completed a driving history questionnaire. MAIN
      OUTCOME MEASURES: Reaction times to the driving simulator divided attention task.
      RESULTS: The mean reaction times to the low-contrast stimulus were 1.05 s and
      0.64 s in glaucoma and controls, respectively, during curve negotiation (P <
      .001), and 1.19 s and 0.77 s (P = .025), respectively, during car following.
      There was a nonlinear relationship between reaction times and RNFL thickness in
      the better eye. RNFL thickness remained significantly associated with reaction
      times even after adjusting for age, SAP mean deviation in the better eye,
      cognitive ability, and central driving task performance. CONCLUSIONS: Although
      worse SAP sensitivity was associated with worse ability to divide attention, RNFL
      thickness measurements provided additional information. Information from
      structural tests may improve our ability to determine which patients are likely
      to have problems performing daily activities, such as driving.

PMID- 25068642
TI  - Computational analysis of microbubble flows in bifurcating airways: role of
      gravity, inertia, and surface tension.
AB  - Although mechanical ventilation is a life-saving therapy for patients with severe
      lung disorders, the microbubble flows generated during ventilation generate
      hydrodynamic stresses, including pressure and shear stress gradients, which
      damage the pulmonary epithelium. In this study, we used computational fluid
      dynamics to investigate how gravity, inertia, and surface tension influence both
      microbubble flow patterns in bifurcating airways and the magnitude/distribution
      of hydrodynamic stresses on the airway wall. Direct interface tracking and finite
      element techniques were used to simulate bubble propagation in a two-dimensional
      (2D) liquid-filled bifurcating airway. Computational solutions of the full
      incompressible Navier-Stokes equation were used to investigate how inertia,
      gravity, and surface tension forces as characterized by the Reynolds (Re), Bond
      (Bo), and Capillary (Ca) numbers influence pressure and shear stress gradients at
      the airway wall. Gravity had a significant impact on flow patterns and
      hydrodynamic stress magnitudes where Bo > 1 led to dramatic changes in bubble
      shape and increased pressure and shear stress gradients in the upper daughter
      airway. Interestingly, increased pressure gradients near the bifurcation point
      (i.e., carina) were only elevated during asymmetric bubble splitting. Although
      changes in pressure gradient magnitudes were generally more sensitive to Ca,
      under large Re conditions, both Re and Ca significantly altered the pressure
      gradient magnitude. We conclude that inertia, gravity, and surface tension can
      all have a significant impact on microbubble flow patterns and hydrodynamic
      stresses in bifurcating airways. 

PMID- 25068643
TI  - Effects of fragmentation and sea-level changes upon frog communities of land
      bridge islands off the southeastern coast of Brazil.
AB  - We investigate the composition of anuran communities of land-bridge islands off
      the southeastern coast of Brazil. These islands provide natural long-term
      experiments on the effects of fragmentation in the Brazilian Atlantic Forest
      (BAF). We hypothesize that Pleistocene sea-level changes, in combination with
      other abiotic variables such as area and habitat diversity, has affected anuran
      species richness and community composition on these islands. Data from the
      literature and collections databases were used to produce species lists for eight
      land-bridge islands and for the mainland adjacent to the islands. We assess the
      effects of area, number of breeding habitats and distance to the mainland upon
      anuran species richness on land-bridge islands. Additionally we use nestedness
      analysis to quantify the extent to which the species on smaller and less habitat
      diverse islands correspond to subsets of those on larger and more diverse ones.
      We found that area has both direct and indirect effects on anuran species
      richness on land-bridge islands, irrespective of distance to the mainland.
      However, on islands with comparable sizes, differences in species richness can be
      attributed to the number and quality of breeding habitats. Anuran communities on
      these islands display a nested pattern, possibly caused by selective extinction
      related to habitat loss. Common lowland pond-breeders were conspicuous by their
      absence. In the BAF, the conservation of fragments with a high diversity of
      breeding habitats could compensate for the generally negative effect of small
      area upon species richness. We suggest that sea-level changes have an important
      role in shaping composition of anuran species on coastal communities. 

PMID- 25068645
TI  - Valproic acid attenuates the suppression of acetyl histone H3 and CREB activity
      in an inducible cell model of Machado-Joseph disease.
AB  - Machado-Joseph disease (MJD) is caused by a (CAG)n trinucleotide repeat expansion
      that is translated into an abnormally long polyglutamine tract. This disease is
      considered the most common form of spinocerebellar ataxia (SCA). In the present
      study, we developed stable inducible cell lines (PC12Tet-On-Ataxin-3-Q28/84)
      expressing ataxin-3 with either normal or abnormal CAG repeats under doxycycline
      control. The expression of acetyl histone H3 and the induction of c-Fos in
      response to cAMP were strongly suppressed in cells expressing the protein with
      the expanded polyglutamine tract. Treatment with valproic acid, a histone
      deacetylase inhibitor (HDACi), attenuated mutant ataxin-3-induced cell toxicity
      and suppression of acetyl histone H3, phosphorylated cAMP-responsive element
      binding protein (p-CREB) as well as c-Fos expression. These results indicate that
      VPA can stimulate the up-regulation of gene transcription through
      hyperacetylation. Thus, VPA might have a therapeutic effect on MJD. 

PMID- 25068644
TI  - Genomes and transcriptomes of partners in plant-fungal-interactions between
      canola (Brassica napus) and two Leptosphaeria species.
AB  - Leptosphaeria maculans 'brassicae' is a damaging fungal pathogen of canola
      (Brassica napus), causing lesions on cotyledons and leaves, and cankers on the
      lower stem. A related species, L. biglobosa 'canadensis', colonises cotyledons
      but causes few stem cankers. We describe the complement of genes encoding
      carbohydrate-active enzymes (CAZys) and peptidases of these fungi, as well as of
      four related plant pathogens. We also report dual-organism RNA-seq transcriptomes
      of these two Leptosphaeria species and B. napus during disease. During the first
      seven days of infection L. biglobosa 'canadensis', a necrotroph, expressed more
      cell wall degrading genes than L. maculans 'brassicae', a hemi-biotroph. L.
      maculans 'brassicae' expressed many genes in the Carbohydrate Binding Module
      class of CAZy, particularly CBM50 genes, with potential roles in the evasion of
      basal innate immunity in the host plant. At this time, three avirulence genes
      were amongst the top 20 most highly upregulated L. maculans 'brassicae' genes in
      planta. The two fungi had a similar number of peptidase genes, and trypsin was
      transcribed at high levels by both fungi early in infection. L. biglobosa
      'canadensis' infection activated the jasmonic acid and salicylic acid defence
      pathways in B. napus, consistent with defence against necrotrophs. L. maculans
      'brassicae' triggered a high level of expression of isochorismate synthase 1, a
      reporter for salicylic acid signalling. L. biglobosa 'canadensis' infection
      triggered coordinated shutdown of photosynthesis genes, and a concomitant
      increase in transcription of cell wall remodelling genes of the host plant.
      Expression of particular classes of CAZy genes and the triggering of host defence
      and particular metabolic pathways are consistent with the necrotrophic lifestyle
      of L. biglobosa 'canadensis', and the hemibiotrophic life style of L. maculans
      'brassicae'. 

PMID- 25068646
TI  - A novel contact model for AFM indentation experiments on soft spherical cell-like
      particles.
AB  - The use of the simple Hertz model for the analysis of Atomic Force Microscopy
      (AFM) force-distance curves measured on soft spherical cell-like particles leads
      to significant underestimations of the objects Young's modulus E. To correct this
      error, a mixed double contact model (based on the simple Hertz model and the
      Johnson-Kendall-Roberts (JKR) model) was derived. The model considers two
      independent particle deformation sites: (i) the upper part of the particle is
      deformed by the AFM indenter, (ii) the bottom part is deformed by the substrate,
      which is usually unnoticed. It becomes apparent that for soft particles even
      small forces between substrate and particle can influence the resulting force
      distance curves. For instance we show, that a gravity-induced compression on the
      particle bottom side can have significant influence on the measurements. To
      highlight these observations, the deviation of the particle Young's modulus E
      between the simple Hertz model and our model is calculated. This error strongly
      depends on the ratio of the three involved radii: (i) the radius of the AFM
      indenter, (ii) the radius of the particle and (iii) the radius of the substrate
      as well as on the acting gravity force. Overall, the analysis suggests that for
      nanoscopic indenters the deviation is negligible, whereas the use of microscopic
      indenters results in significant errors that can be corrected via the presented
      model. This is important especially for very soft particles, since larger
      indenters can achieve higher signal to noise ratios. Furthermore, the
      applicability of the model was confirmed by indentation experiments on hydrogel
      microbeads. The mixed double contact model is applicable to a large range of
      indenter geometries and can be adapted for other contact models. 

PMID- 25068647
TI  - Semaphorin 3F and neuropilin-2 control the migration of human T-cell precursors.
AB  - Neuropilins and semaphorins are known as modulators of axon guidance,
      angiogenesis, and organogenesis in the developing nervous system, but have been
      recently evidenced as also playing a role in the immune system. Here we describe
      the expression and role of semaphorin 3F (SEMA3F) and its receptor neuropilin-2
      (NRP2) in human T cell precursors. NRP2 and SEMA3F are expressed in the human
      thymus, in both lymphoid and non-lymphoid compartments. SEMA3F have a repulsive
      effect on thymocyte migration and inhibited CXCL12- and sphingosine-1-phosphate
      (S1P)-induced thymocyte migration by inhibiting cytoskeleton reorganization prior
      to stimuli. Moreover, NRP2 and SEMA3F are expressed in human T-cell acute
      lymphoblastic leukemia/lymphoma primary cells. In these tumor cells, SEMA3F also
      blocks their migration induced by CXCL12 and S1P. Our data show that SEMA3F and
      NRP2 are further regulators of human thymocyte migration in physiological and
      pathological conditions. 

PMID- 25068649
TI  - Ultralow interfacial tensions of aqueous two-phase systems measured using drop
      shape.
AB  - Aqueous solutions of different polymers can separate and form aqueous two-phase
      systems (ATPS). ATPS provide an aqueous, biocompatible, and mild environment for
      separation and fractionation of biomolecules. The interfacial tension between the
      two aqueous phases plays a major role in ATPS-mediated partition of biomolecules.
      Because of the structure of the two aqueous phases, the interfacial tensions
      between the phases can be 3-4 orders of magnitude smaller than conventional fluid
      liquid systems: ~1-100 MUJ/m(2) for ATPS compared to ~72 mJ/m(2) for the water
      vapor interface. This poses a major challenge for the experimental measurements
      of reproducible interfacial tension data for these systems. We address the need
      for precise determination of ultralow interfacial tensions by systematically
      studying a series of polymeric ATPS comprising of polyethylene glycol (PEG) and
      dextran (DEX) as the phase-forming polymers. Sessile and pendant drops of the
      denser DEX phase are formed within the immersion PEG phase. An axisymmetric drop
      shape analysis (ADSA) is used to determine interfacial tensions of eight
      different ATPS. Specific criteria are used to reproducibly determine ultralow
      interfacial tensions of the ATPS from pendant and sessile drops. Importantly, for
      a given ATPS, pendant drop and sessile drop experiments return values within
      0.001 mJ/m(2) indicating reliability of our measurements. Then, the pendant drop
      technique is used to measure interfacial tensions of all eight ATPS. Our measured
      values range from 0.012 +/- 0.001 mJ/m(2) to 0.381 +/- 0.006 mJ/m(2) and vary
      with the concentration of polymers in equilibrated phases of ATPS. Measurements
      of ultralow interfacial tensions with such reproducibility will broadly benefit
      studies involving partition of different biomolecules in ATPS and elucidate the
      critical effect of interfacial tension. 

PMID- 25068650
TI  - Identification and use of an alkane transporter plug-in for applications in
      biocatalysis and whole-cell biosensing of alkanes.
AB  - Effective application of whole-cell devices in synthetic biology and biocatalysis
      will always require consideration of the uptake of molecules of interest into the
      cell. Here we demonstrate that the AlkL protein from Pseudomonas putida GPo1 is
      an alkane import protein capable of industrially relevant rates of uptake of C7
      C16 n-alkanes. Without alkL expression, native E.coli n-alkane uptake was the
      rate-limiting step in both the whole-cell bioconversion of C7-C16 n-alkanes and
      in the activation of a whole-cell alkane biosensor by C10 and C11 alkanes. By
      coexpression of alkL as a transporter plug-in, specific yields improved by up to
      100-fold for bioxidation of >C12 alkanes to fatty alcohols and acids. The alkL
      protein was shown to be toxic to the host when overexpressed but when expressed
      from a vector capable of controlled induction, yields of alkane oxidation were
      improved a further 10-fold (8 g/L and 1.7 g/g of total oxidized products).
      Further testing of activity on n-octane with the controlled expression vector
      revealed the highest reported rates of 120 MUmol/min/g and 1 g/L/h total oxidized
      products. This is the first time AlkL has been shown to directly facilitate
      enhanced uptake of C10-C16 alkanes and represents the highest reported gain in
      product yields resulting from its use.

PMID- 25068651
TI  - Sufficient Volume Ablation with Photoselective Vaporization of the Prostate
      Delivers 5-Year Durability and Improves Symptom Relief for Larger Prostates.
AB  - OBJECTIVES: To assess the long-term durability of photoselective vaporization of
      the prostate (PVP) for symptomatic benign prostatic enlargement (BPE) or benign
      prostatic obstruction (BPO) and treatment efficacy for large BPE. METHODS: Four
      hundred fifty-seven patients with symptomatic BPE underwent PVP between January
      2006 and April 2009. Efficacy was evaluated with the International Prostate
      Symptoms Score (IPSS), Quality of Life (QOL) score, urinary peak flow (Qmax),
      postvoid residual volume (PVR), and prostate volume. Parameters were checked
      preoperatively, and at 1, 3, and 5 years postoperatively. One hundred fifty-three
      patients completed 5-year follow-up. To assess treatment effects, patients were
      divided into two groups according to the preoperative prostate volume: group A
      (<60 mL, n=104) and group B (>60 mL, n=49). RESULTS: Mean IPSS, QOL score, Qmax,
      and PVR improved significantly and were maintained for 5 years with no
      significant differences; at year 1, prostate volume had decreased significantly
      from 54.0 mL to 30.6 mL (43% of volume ablation) and remained at that level until
      year 5. Investigations according to prostate size demonstrate that IPSS and QOL
      scores in group B remained at significantly lower levels, and Qmax in group B
      improved more than in group A. 1.1% of patients needed transurethral resection of
      the prostate due to BPO recurrence. CONCLUSIONS: PVP is effective and provides
      durable results for 5 years, with sustained symptom relief and improved urinary
      flow rate, as well as a 43% volume reduction of prostate volume. Our data
      indicate PVP is more efficacious for larger prostates under sufficient volume
      ablation.

PMID- 25068652
TI  - Maternal antenatal anxiety, postnatal stroking and emotional problems in
      children: outcomes predicted from pre- and postnatal programming hypotheses.
AB  - BACKGROUND: Mothers' self-reported stroking of their infants over the first weeks
      of life modifies the association between prenatal depression and physiological
      and emotional reactivity at 7 months, consistent with animal studies of the
      effects of tactile stimulation. We now investigate whether the effects of
      maternal stroking persist to 2.5 years. Given animal and human evidence for sex
      differences in the effects of prenatal stress we compare associations in boys and
      girls. METHOD: From a general population sample of 1233 first-time mothers
      recruited at 20 weeks gestation we drew a random sample of 316 for assessment at
      32 weeks, stratified by reported inter-partner psychological abuse, a risk
      indicator for child development. Of these mothers, 243 reported at 5 and 9 weeks
      how often they stroked their infants, and completed the Child Behavior Checklist
      (CBCL) at 2.5 years post-delivery. RESULTS: There was a significant interaction
      between prenatal anxiety and maternal stroking in the prediction of CBCL
      internalizing (p = 0.001) and anxious/depressed scores (p < 0.001). The effects
      were stronger in females than males, and the three-way interaction prenatal
      anxiety * maternal stroking * sex of infant was significant for internalizing
      symptoms (p = 0.003). The interactions arose from an association between prenatal
      anxiety and internalizing symptoms only in the presence of low maternal stroking.
      CONCLUSIONS: The findings are consistent with stable epigenetic effects, many sex
      specific, reported in animal studies. While epigenetic mechanisms may be
      underlying the associations, it remains to be established whether stroking
      affects gene expression in humans.

PMID- 25068653
TI  - Oxidative stress mediates the conversion of endothelial cells into myofibroblasts
      via a TGF-beta1 and TGF-beta2-dependent pathway.
AB  - During the pathogenesis of systemic inflammation, reactive oxygen species (ROS)
      circulate in the bloodstream and interact with endothelial cells (ECs),
      increasing intracellular oxidative stress. Although endothelial dysfunction is
      crucial in the pathogenesis of systemic inflammation, little is known about the
      effects of oxidative stress on endothelial dysfunction. Oxidative stress induces
      several functions, including cellular transformation. A singular process of cell
      conversion is tendothelial-to-mesenchymal transition, in which ECs become
      myofibroblasts, thus losing their endothelial properties and gaining fibrotic
      behavior. However, the participation of oxidative stress as an inductor of
      conversion of ECs into myofibroblasts is not known. Thus, we studied the role
      played by oxidative stress in this conversion and investigated the underlying
      mechanism. Our results show that oxidative stress induces conversion of ECs into
      myofibroblasts through decreasing the levels of endothelial markers and
      increasing those of fibrotic and ECM proteins. The underlying mechanism depends
      on the ALK5/Smad3/NF-kappaB pathway. Oxidative stress induces the expression and
      secretion of TGF-beta1 and TGF-beta2 and p38 MAPK phosphorylation. Downregulation
      of TGF-beta1 and TGF-beta2 by siRNA technology abolished the H2O2-induced
      conversion. To our knowledge, this is the first report showing that oxidative
      stress is able to induce conversion of ECs into myofibroblasts via TGF-beta
      secretion, emerging as a source for oxidative stress-based vascular dysfunction.
      Thus, oxidative stress emerges as a decisive factor in inducing conversion of ECs
      into myofibroblasts through a TGF-beta-dependent mechanism, changing the ECs
      protein expression profile, and converting normal ECs into pathological ones.
      This information will be useful in designing new and improved therapeutic
      strategies against oxidative stress-mediated systemic inflammatory diseases. 

PMID- 25068654
TI  - Activin A balance regulates epithelial invasiveness and tumorigenesis.
AB  - Activin A (Act A) is a member of the TGFbeta superfamily. Act A and TGFbeta have
      multiple common downstream targets and have been described to merge in their
      intracellular signaling cascades and function. We have previously demonstrated
      that coordinated loss of E-cadherin and TGFbeta receptor II (TbetaRII) results in
      epithelial cell invasion. When grown in three-dimensional organotypic reconstruct
      cultures, esophageal keratinocytes expressing dominant-negative mutants of E
      cadherin and TbetaRII showed activated Smad2 in the absence of functional
      TbetaRII. However, we could show that increased levels of Act A secretion was
      able to induce Smad2 phosphorylation. Growth factor secretion can activate
      autocrine and paracrine signaling, which affects crosstalk between the epithelial
      compartment and the surrounding microenvironment. We show that treatment with the
      Act A antagonist Follistatin or with a neutralizing Act A antibody can increase
      cell invasion in organotypic cultures in a fibroblast- and MMP-dependent manner.
      Similarly, suppression of Act A with shRNA increases cell invasion and
      tumorigenesis in vivo. Therefore, we conclude that maintaining a delicate balance
      of Act A expression is critical for homeostasis in the esophageal
      microenvironment. 

PMID- 25068655
TI  - Flow cytometry analysis of synaptosomes from post-mortem human brain reveals
      changes specific to Lewy body and Alzheimer's disease.
AB  - Synaptic dysfunction is thought to have an important role in the pathophysiology
      of neurodegenerative diseases, such as Alzheimer's disease (AD) and Lewy body
      disease (LBD). To improve our understanding of synaptic alterations in health and
      disease, we investigated synaptosomes prepared from post-mortem human cerebral
      cortex, putamen (PT), and two regions of the caudate nucleus, dorso-lateral (DL)
      and ventro-medial (VM), regions commonly affected in AD and LBD. We observed that
      the fraction of synaptosomal particles with reactivity for dopamine transporter
      (DAT) was significantly reduced in the PT and VM caudate of patients with
      neuropathological diagnosis of LBD. As expected, these differences also were
      reflected in direct measurements of dopamine (DA) and its metabolite, 3,4
      dihydroxyphenylacetic acid (DOPAC), in caudate and PT of LBD patients. The
      fraction of synaptosomal particles positive for amyloid beta (Abeta) was
      significantly increased in frontal cortical samples of patients with the
      neuropathological diagnosis of severe AD, and was positively correlated with
      disease progression. We also prepared synaptosomes from the striatum of mice with
      severe loss of DA neurons (Slc6a3-DTR mice) and wild-type littermate controls. We
      observed markedly reduced levels of DAT-positive synaptosomes in Slc6a3-DTR mice
      following exposure to diphtheria toxin (DT). Striatal levels of DA and DOPAC in
      Slc6a3-DTR mice also were reduced significantly following DT exposure. We
      conclude that flow cytometric analysis of synaptosomes prepared from human or
      mouse brain provides an opportunity to study expression of pathology-associated
      proteins and also the specific loss of dopaminergic nerve terminals. Hence, we
      believe it is a valid method to detect pathological changes at the level of the
      synapse in LBD as well as AD. 

PMID- 25068656
TI  - Hepatic cytochrome P450 deficiency in mouse models for intrahepatic cholestasis
      predispose to bile salt-induced cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) types 1 and 3 are severe
      cholestatic liver diseases caused by deficiency of ATB8B1 and ABCB4,
      respectively. Mouse models for PFIC display mild phenotypes compared with human
      patients, and this can be explained by the difference in bile salt pool
      composition. Mice, unlike humans, have the ability to detoxify hydrophobic bile
      salts by cytochrome P450-mediated (re)hydroxylation and thus have a less toxic
      bile salt pool. We have crossed mouse models for PFIC1 and PFIC3 with Hrn mice
      that have a reduced capacity to (re)hydroxylate bile salts. Double transgenes
      were obtained by backcrossing Atp8b1(G308V/G308V) and Abcb4(-/-) mice with Hrn
      mice that have a liver-specific disruption of the cytochrome P450 reductase gene
      and therefore have markedly reduced P450 activity. In these mice, a more
      hydrophobic bile salt pool was instilled by cholic acid supplementation of the
      diet, and bile formation and liver pathology was studied. As opposed to single
      transgenes, Atp8b1(G308V/G308V)/Hrn and Abcb4(-/-)/Hrn mice rapidly developed
      strong cholestasis that was evidenced by increased plasma bilirubin and bile salt
      levels. The bile salt pool was more toxic in both models; Atp8b1(G308V/G308V)/Hrn
      mice had a more hydrophobic plasma pool compared with the single transgene,
      whereas Abcb4(-/-)/Hrn mice had a more hydrophobic biliary pool compared with the
      single transgene. In line with these findings, liver damage was not aggravated in
      Atp8b1(G308V/G308V)/Hrn but was more severe in Abcb4(-/-)/Hrn mice. These data
      indicate that bile salt pool composition is a critical determinant in the
      initiation and progression of cholestasis and liver pathology in PFIC1 and PFIC3.
      Most importantly, our data suggest that the hydrophobicity of the plasma bile
      salt pool is an important determinant of the severity of cholestasis, whereas the
      hydrophobicity of the biliary bile salt pool is an important determinant of the
      severity of liver pathology. 

PMID- 25068657
TI  - Lactoferrin suppresses the Epstein-Barr virus-induced inflammatory response by
      interfering with pattern recognition of TLR2 and TLR9.
AB  - Epstein-Barr virus (EBV) infection contributes to tumorigenesis of various human
      malignancies including nasopharyngeal carcinoma (NPC). EBV triggers innate immune
      and inflammatory responses partly through Toll-like receptor (TLR) signaling.
      Lactoferrin (LF), with its anti-inflammatory properties, is an important
      component of the innate immune system. We previously reported that LF protects
      human B lymphocytes from EBV infection by its ability to bind to the EBV receptor
      CD21, but whether LF can suppress EBV-induced inflammation is unclear. Here, we
      report that LF reduced synthesis of IL-8 and monocyte chemoattractant protein-1
      (MCP-1) induced by EBV in macrophages via its suppression of NF-kappaB activity.
      LF interacted with TLR2 and interfered with EBV-triggered TLR2-NF-kappaB
      activation. LF inhibited the ability of TLR9 to recognize dsDNA by binding to its
      co-receptor CD14, which blocked the interaction between CD14 and TLR9. EBV
      induced inflammation was thus aggravated in the presence of CD14. In addition, LF
      expression levels were significantly downregulated in NPC specimens, and
      correlated inversely with IL-8 and MCP-1 expression. These findings suggest that
      LF may suppress the EBV-induced inflammatory response through interfering with
      the activation of TLR2 and TLR9. 

PMID- 25068658
TI  - The microbiota regulates susceptibility to Fas-mediated acute hepatic injury.
AB  - Whereas a significant role for intestinal microbiota in affecting the
      pathogenesis and progression of chronic hepatic diseases is well documented, the
      contribution of the intestinal flora to acute liver injury has not been
      extensively addressed. Elucidating the influence of the intestinal microbiota on
      acute liver inflammation would be important for better understanding the
      transition from acute injury to chronic liver disease. Using the Concanavalin A
      (ConA)-induced liver injury model in laboratory mice, we show that the severity
      of acute hepatic damage varies greatly among genetically identical mice raised in
      different environments and harboring distinct microbiota. Through reconstitution
      of germ-free (GF) mice, and the co-housing of conventional mice, we provide
      direct evidence that manipulation of the intestinal flora alters susceptibility
      to ConA-induced liver injury. Through deep sequencing of the fecal microbiome, we
      observe that the relative abundance of Ruminococcaceae, a Gram(+) family within
      the class Clostridia, but distinct from segmented filamentous bacteria, is
      positively associated with the degree of liver damage. Searching for the
      underlying mechanism(s) that regulate susceptibility to ConA, we provide evidence
      that the extent of liver injury following triggering of the death receptor Fas
      varies greatly as a function of the microbiota. We demonstrate that the extent of
      Fas-induced liver injury increases in GF mice after microbiota reconstitution,
      and decreases in conventionally raised mice following reduction in intestinal
      bacterial load, by antibiotic treatment. We also show that the regulation of
      sensitivity to Fas-induced liver injury is dependent upon the toll-like receptor
      signaling molecule MyD88. In conclusion, the status and composition of the
      intestinal microbiota determine the susceptibility to ConA-induced acute liver
      injury. The microbiota acts as a rheostat, actively modulating the extent of
      liver damage in response to Fas triggering. 

PMID- 25068659
TI  - TRPA1 is required for TGF-beta signaling and its loss blocks inflammatory
      fibrosis in mouse corneal stroma.
AB  - We examined whether the loss of transient receptor potential ankyrin 1 (TRPA1),
      an irritant-sensing ion channel, or TRPA1 antagonist treatment affects the
      severity inflammation and scarring during tissue wound healing in a mouse cornea
      injury model. In addition, the effects of the absence of TRPA1 on transforming
      growth factor beta1 (TGF-beta1)-signaling activation were studied in cell
      culture. The lack of TRPA1 in cultured ocular fibroblasts attenuated expression
      of TGF-beta1, interleukin-6, and alpha-smooth muscle actin, a myofibroblast the
      marker, but suppressed the activation of Smad3, p38 MAPK, ERK, and JNK. Stroma of
      the healing corneas of TRPA1(-/-) knockout (KO) mice appeared more transparent
      compared with those of wild-type mice post-alkali burn. Eye globe diameters were
      measured from photographs. An examination of the corneal surface and eye globes
      suggested the loss of TRPA1 suppressed post-alkali burn inflammation and
      fibrosis/scarring, which was confirmed by histology, immunohistochemistry, and
      gene expression analysis. Reciprocal bone marrow transplantation between mice
      showed that KO corneal tissue resident cells, but not KO bone marrow-derived
      cells, are responsible for KO mouse wound healing with reduced inflammation and
      fibrosis. Systemic TRPA1 antagonists reproduced the KO phenotype of healing. In
      conclusion, a loss or blocking of TRPA1 in mice reduces inflammation and
      fibrosis/scarring in the corneal stroma during wound healing following an alkali
      burn. The responsible mechanism may include the inhibition of TGF-beta1-signaling
      cascades in fibroblasts by attenuated TRPA1 signaling. Inflammatory cells are
      considered to have a minimum involvement in the exhibition of the KO phenotype
      after injury. 

PMID- 25068660
TI  - Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation
      and colitis-associated cancer.
AB  - Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the
      gastrointestinal (GI) tract associated with an increased risk of colorectal
      cancer (CRC). Current treatments for both IBD and colitis-associated CRC suffer
      from numerous side effects. Parthenolide (PTL) is a sesquiterpene lactone with
      anti-inflammatory activity, and previous studies have demonstrated that PTL is a
      potent inhibitor of the NF-kappaB pathway. Micheliolide (MCL), substantially more
      stable than PTL in vivo, was recently developed, and this study aimed to decipher
      its suitability as therapeutic tool for IBD and IBD-associated diseases. Similar
      to PTL, MCL inhibited NF-kappaB activation and subsequent pro-inflammatory
      pathways activation in vitro. Pro-drug forms of both compounds inhibited the DSS
      induced colitis when administrated intraperitoneally or encapsulated in a
      polysaccharide gel designed to release drugs in the colon. Interestingly, MCL was
      found to attenuate carcinogenesis in AOM/DSS-induced CRC, thus providing new
      candidate for the treatment of inflammatory bowel disease and CRC. 

PMID- 25068661
TI  - Detection of somatic mutations in tumors using unaligned clonal sequencing data.
AB  - Most cancers arise and evolve as a consequence of somatic mutations. These
      mutations influence tumor behavior and clinical outcome. Consequently, there is
      considerable interest in identifying somatic variants within specific genes (such
      as BRAF, KRAS and EGFR) so that chemotherapy can be tailored to the patient's
      tumor genotype rather than using a generic treatment based on histological
      diagnosis alone. Owing to the heterogeneous nature of tumors, a somatic mutation
      may be present in only a subset of cells, necessitating the use of quantitative
      techniques to detect rare variants. The highly quantitative nature of next
      generation sequencing (NGS), together with the ability to multiplex numerous
      samples, makes NGS an attractive choice with which to screen for somatic
      variants. However, the large volumes of sequence data present significant
      difficulties when applying NGS for the detection of somatic mutations. To
      alleviate this, we have developed methodologies including a set of data analysis
      programs, which allow the rapid screening of multiple formalin-fixed, paraffin
      embedded samples for the presence of specified somatic variants using unaligned
      Illumina NGS data. 

PMID- 25068663
TI  - Rhythmic priming enhances speech production abilities: evidence from prelingually
      deaf children.
AB  - OBJECTIVE: Following recent findings that rhythmic priming can enhance speech
      perception, the aim of this experiment was to investigate whether this extends to
      speech production. METHOD: The authors measured the influence of rhythmic priming
      on phonological production abilities in 14 hearing impaired children with hearing
      devices. Children had to repeat sentences that were or were not preceded by a
      rhythmical prime. In addition, this rhythmic prime either matched or mismatched
      the meter (i.e., stress contrasts) of the sentence. RESULTS: Matching conditions
      resulted in a greater phonological accuracy of spoken sentences compared to
      baseline and mismatching conditions. Cochlear implant users were also more
      sensitive to rhythmic priming than hearing aid users. CONCLUSIONS: These results
      suggest that musical rhythmic priming can enhance phonological production in HI
      children via an enhanced perception of the target sentence. Overall, these
      findings suggest that musical rhythm engages domain-general expectations which
      can enhance both in perception and production of speech.

PMID- 25068662
TI  - Renal expression of advanced oxidative protein products predicts progression of
      renal fibrosis in patients with IgA nephropathy.
AB  - Predicting the risk of disease progression in IgA nephropathy (IgAN) remains a
      challenge. This study was conducted to test the hypothesis that renal
      accumulation of advanced oxidized protein products (AOPPs) is an early predictor
      for renal progression in IgAN. This was a single-center prospective cohort study.
      One hundred IgAN patients with eGFR>80 ml/min/1.73 m(2) were enrolled. Seventy
      seven patients were followed for a mean of 4.2 years, and 30 patients received
      repeat renal biopsy at a mean of 42 months after diagnosis. The outcomes were the
      progression of renal fibrosis and rapid progression of CKD (>5 ml/min/1.73
      m(2)/year) during follow-up. Immunoreactivity of AOPPs was detected predominantly
      in tubular epithelial cells and co-localized with expression of TGF-beta1 and
      angiotensin II. Renal staining score of AOPPs at diagnosis was associated with
      the level of tissue cellular inflammation. Accumulation of AOPPs, particularly in
      interstitial-infiltrating cells, was negatively correlated with changes of eGFR
      during follow-up; those with expression scores greater than the median at
      diagnosis had significantly higher incidences of rapid decline of eGFR compared
      with those with the score less than or equal to the median. For patients who
      received repeat renal biopsy, renal AOPP levels greater than the median at
      diagnosis were associated with increase in renal fibrosis index at repeat biopsy.
      After multivariate adjustment, renal AOPP expression was an independent predictor
      for progression of renal fibrosis and rapid decline of eGFR. Taken together,
      these results demonstrate that renal AOPPs might be a predictor, detectable at
      the time of diagnosis, for renal progression in patients with early stage IgAN. 

PMID- 25068664
TI  - Retrograde memory for public events in mild cognitive impairment and its
      relationship to anterograde memory and neuroanatomy.
AB  - OBJECTIVE: The study characterized the status of retrograde amnesia (RA) in
      amnestic mild cognitive impairment (MCI). METHOD: We measured RA, anterograde
      amnesia (AA), brain measures, apolipoprotein-E status (ApoE), and conversion to
      probable Alzheimer's disease (AD) across 3 years in 15 individuals with MCI. We
      compared the severity of amnesia and brain atrophy in MCI to a group of patients
      with limited damage to the hippocampus (H) or more extensive damage to the medial
      temporal lobe (MTL). RESULTS: The MCI group exhibited modest AA, together with
      severe RA, covering nearly 4 decades before their diagnosis. Compared with H-MTL
      patients, the temporal extent of RA was disproportionate to the severity of AA.
      The MCI group exhibited more modest AA and MTL atrophy than H-MTL patients,
      together with more severe RA and neocortical atrophy than H-MTL patients. The
      severity of AA corresponded to the integrity of MTL structures, whereas the
      severity of RA corresponded to the integrity of both MTL and neocortical
      structures. RA (but not AA, nor measures of cognitive status) was related to ApoE
      status and subsequent diagnosis of probable AD. RA was predicted by heritable
      risk for AD, in addition to the integrity of MTL and neocortical structures.
      CONCLUSIONS: Compared with H-MTL patients, the MCI group exhibited RA that was
      disproportionate to their AA and that was more severe than would be expected if
      their atrophy were limited primarily to the MTL. Heritable risk for AD, as well
      as the integrity of brain regions within and beyond the MTL, are important for
      understanding RA in MCI.

PMID- 25068666
TI  - Characterization and prediction of theory of mind disorders in temporal lobe
      epilepsy.
AB  - OBJECTIVE: Patients with temporal lobe epilepsy (TLE) have impaired theory of
      mind (ToM). However, ToM involves a variety of processes, such as understanding a
      person's intentions ("cognitive" ToM) and emotional states ("affective" ToM). The
      objectives of the present study were to characterize ToM disorders in TLE
      patients, identify patients at risk of ToM disorders, and study the relationships
      between psychobehavioral and quality of life factors and ToM disorders. METHOD:
      Fifty TLE patients and 50 controls performed ToM tasks assessing their
      understanding of verbal clumsiness (faux pas), sarcastic remarks, and mentalistic
      actions. Demographic, cognitive, and psychobehavioral data, and (for TLE
      patients) clinical and quality of life factors, were recorded. RESULTS: Compared
      with controls, TLE patients showed impairments in all ToM tasks: 84%
      misunderstood faux pas, and around 50% misunderstood sarcasm. A long duration of
      epilepsy and young age at onset were risk factors for ToM impairments. In TLE
      patients, ToM impairments were associated with impaired empathy and anhedonia.
      Their affective states were less positively and more negatively valenced than in
      controls. Low positive affectivity was predictive of greater cognitive and
      affective ToM impairments for the faux pas task, and high negative affectivity
      was predictive of greater cognitive ToM abilities for the sarcasm task. The lack
      of social support was correlated with impaired ToM but was not a predictive
      factor. CONCLUSIONS: Both cognitive and affective ToM processes are impaired in
      TLE patients. Impaired ToM has an impact on empathy abilities and is related to
      affective disturbances in TLE patients.

PMID- 25068667
TI  - Reduced hippocampal volume is associated with overgeneralization of negative
      context in individuals with PTSD.
AB  - OBJECTIVE: Previous studies demonstrated reduced hippocampal volume in
      individuals with posttraumatic stress disorder (PTSD). However, the functional
      role the hippocampus plays in PTSD symptomatology is still unclear. The aim of
      the present study was to explore generalization learning and its connection to
      hippocampal volume in individuals with and without PTSD. Animal and human models
      argue that hippocampal deficit may result in failure to process contextual
      information. Therefore we predicted associations between reduced hippocampal
      volume and overgeneralization of context in individuals with PTSD. METHOD: We
      conducted MRI scans of bilateral hippocampal and amygdala formations as well as
      intracranial and total brain volumes. Generalization was measured using a novel
      learning paradigm, which separately evaluates generalization of cue and context
      in conditions of negative and positive outcomes. RESULTS: As expected, MRI scans
      indicated reduced hippocampal volume in PTSD compared to non-PTSD participants.
      Behavioral results revealed a selective deficit in context generalization
      learning in individuals with PTSD, F(1, 43) = 8.27, p < .01, eta(p)2 = .16.
      Specifically, as predicted, while generalization of cue was spared in both
      groups, individuals with PTSD showed overgeneralization of negative context.
      Hence, they could not learn that a previously negative context is later
      associated with a positive outcome, F(1, 43) = 7.33, p = .01, eta(p)2 = .15. Most
      importantly, overgeneralization of negative context significantly correlated with
      right and left hippocampal volume (r = .61, p = .000; r = .5, p = .000). Finally,
      bilateral hippocampal volume provided the strongest prediction of
      overgeneralization of negative context. CONCLUSIONS: Reduced hippocampal volume
      may account for the difficulty of individuals with PTSD to differentiate negative
      and novel conditions and hence may facilitate reexperiencing symptoms.

PMID- 25068668
TI  - Attention shifting in Parkinson's disease: an analysis of behavioral and cortical
      responses.
AB  - OBJECTIVE: The study was designed to examine persistent (input selection) versus
      transient (input shifting) mechanisms of attention control in Parkinson's disease
      (PD). METHOD: The study identifies behavioral and neural markers of selective
      control and shifting control using a novel combination of a flanker task with an
      attentional set-shifting task, and it compares patients with PD with matched
      controls. Event-related brain potentials (ERPs) were recorded, and analyses
      focused on frontally distributed N2 waves, parietally distributed P3 waves, and
      error-related negativities (Ne/ERN). RESULTS: Controls showed robust shifting
      costs (prolonged response times), but patients with PD did not show evidence for
      comparable shifting costs. Patients with PD made more errors than controls when
      required to shift between attentional sets, but also when they had to initially
      maintain an attentional set. At the neural level it was found that contrary to
      controls, patients with PD did not display any N2 and P3 augmentations on shift
      trials. Patients with PD further did not display any error-related activity or
      posterror N2 augmentation. CONCLUSIONS: Our results reveal that intact selective
      control and disrupted shifting control are dissociable in patients with PD, but
      additional work is required to dissect the proportionate effects of disease and
      treatment on shifting control in PD. Our ERP-based approach opens a new window
      onto an understanding of motor and cognitive flexibility that seems to be
      associated with the dopaminergic innervation of cortico-striatal loops.

PMID- 25068665
TI  - Memory for items and relationships among items embedded in realistic scenes:
      disproportionate relational memory impairments in amnesia.
AB  - OBJECTIVE: The objective of this study was to examine the dependence of item
      memory and relational memory on medial temporal lobe (MTL) structures. Patients
      with amnesia, who either had extensive MTL damage or damage that was relatively
      restricted to the hippocampus, were tested, as was a matched comparison group.
      Disproportionate relational memory impairments were predicted for both patient
      groups, and those with extensive MTL damage were also expected to have impaired
      item memory. METHOD: Participants studied scenes, and were tested with
      interleaved 2-alternative forced-choice probe trials. Probe trials were either
      presented immediately after the corresponding study trial (Lag 1), 5 trials later
      (Lag 5), or 9 trials later (Lag 9) and consisted of the studied scene along with
      a manipulated version of that scene in which 1 item was replaced with a different
      exemplar (item memory test) or was moved to a new location (relational memory
      test). Participants were to identify the exact match of the studied scene.
      RESULTS: As predicted, patients were disproportionately impaired on the test of
      relational memory. Item memory performance was marginally poorer among patients
      with extensive MTL damage, but both groups were impaired relative to matched
      comparison participants. Impaired performance was evident at all lags, including
      the shortest possible lag (Lag 1). CONCLUSIONS: The results are consistent with
      the proposed role of the hippocampus in relational memory binding and
      representation, even at short delays, and suggest that the hippocampus may also
      contribute to successful item memory when items are embedded in complex scenes.

PMID- 25068669
TI  - Functional neuroimaging of the Iowa Gambling Task in older adults.
AB  - OBJECTIVE: The neural systems most susceptible to age-related decline mirror the
      systems linked to decision making. Yet, the neural processes underlying decision
      making disparities among older adults are not well understood. We sought to
      identify neural response patterns that distinguish 2 groups of older adults who
      exhibit divergent decision-making patterns. METHOD: Participants were 31 healthy
      older adults (ages 59-88, 53% female), defined as advantageous or disadvantageous
      decision-makers based on Iowa Gambling Task (IGT) performance, who completed an
      alternate version of the IGT while undergoing functional MRI. The groups were
      indistinguishable on neuropsychological testing. We contrasted the BOLD signal
      between groups during 3 phases of the decision-making process: Prechoice
      (preselection), Prefeedback (postselection), and Feedback (receipt of
      gains/losses). We further examined whether BOLD signal varied as a function of
      age in each group. RESULTS: We observed greater activation among the IGT
      Disadvantageous relative to -Advantageous older adults in the prefrontal cortex
      during the early phases of the decision-making process (Prechoice), and in
      posterior brain regions (e.g., the precuneus) during the later phases
      (Prefeedback and Feedback). We also found that with increasing age, IGT
      Advantageous older adults showed increasing activation in the prefrontal cortex
      during all phases and increasing activation in the posterior cingulate during
      earlier phases of the decision process. By contrast, the IGT-Disadvantageous
      older adults exhibited a reduced or reversed trend. CONCLUSIONS: These functional
      differences may be a consequence of altered reward processing or differing
      compensatory strategies between IGT-Disadvantageous and -Advantageous older
      adults. This supports the notion that divergent neurobiological aging
      trajectories underlie disparate decision-making patterns.

PMID- 25068671
TI  - Evidence cerebral blood-flow regulation mediates exercise-cognition links in
      healthy young adults.
AB  - OBJECTIVE: Healthy young adults are presumed to be in their cognitive prime, yet
      emerging evidence indicates that regular engagement in physical activity can
      still benefit their cognitive functioning. The mechanisms supporting these
      exercise-related cognitive benefits remain unclear, but recent research points to
      cerebral blood-flow (CBF) regulation as potentially important. The current study
      investigated the possibility that efficacy of CBF regulation underpins exercise
      cognition links in this high functioning population. METHOD: In 55 healthy young
      adults, cognitive control performance (inhibition and switching) was examined in
      relation to habitual physical activity, aerobic fitness, and CBF regulation
      (evidenced by blood-flow responsiveness to increases and decreases in carbon
      dioxide: hypercapnic reactivity, n = 43, and hypocapnic reactivity, n = 42).
      RESULTS: Multiple regression analyses revealed that more frequent physical
      activity, and to some extent better aerobic fitness, predicted both better CBF
      regulation and better cognitive inhibitory control. CBF regulation also predicted
      better cognitive inhibitory control. Moreover, mediation analyses indicated that
      more frequent participation in physical activity may bring about improvements in
      cognitive inhibitory control through improved CBF regulation. CONCLUSION: These
      results provide novel insight into the cognitive and cerebrovascular benefits
      that may be gained with regular engagement in physical activity, even in a high
      functioning population. Moreover, they point to better CBF regulation as a
      specific mechanism that may drive physical activity-related cognitive benefits,
      which converges with recent data in older women (Brown et al., 2010).

PMID- 25068670
TI  - Prospective and episodic memory in relation to hippocampal volume in adults with
      spina bifida myelomeningocele.
AB  - The present study examined prospective and episodic memory in relation to age,
      functional independence, and hippocampal volume in younger to middle-aged adults
      with spina bifida myelomeningocele (SBM) and typically developing (TD) adults.
      Prospective and episodic memory, as well as hippocampal volume, was reduced in
      adults with SBM relative to TD adults. Neither memory performance nor hippocampal
      volume showed greater decrements in older adults. Lower hippocampal volume was
      associated with reduced prospective memory in adults with SBM, and this relation
      was specific to the hippocampus and not to a contrast structure, the amygdala.
      Prospective memory mediated the relation between hippocampal volume and
      functional independence in adults with SBM. The results add to emerging evidence
      for reduced memory function in adults with SBM and provide quantitative evidence
      for compromised hippocampal macrostructure as a neural correlate of reduced
      memory in this population.

PMID- 25068672
TI  - Is radical-by-radical reading strategy effective for Chinese pure alexia? A case
      study.
AB  - OBJECTIVE: Currently, it is unclear whether a radical-by-radical (RBR) reading
      strategy exists in Chinese pure alexia, compared to the letter-by-letter (LBL)
      reading strategy in alphabetic languages. In this study, we focus on exploring
      the reading features of a Chinese pure alexic patient during the process of
      language recovery. METHOD: We investigated this issue using a series of
      neuropsychological tests at 4 days, 11 days, and 8 months after admission of a
      Chinese pure alexic patient. RESULTS: The results showed that most words could
      not be read aloud initially by the patient. One week later, 2 clinical features
      were noted: RBR reading strategy and integration impairment. Finally, there were
      statistically significant differences in the reaction time between the single
      characters and compound characters, which indicated that a radical number effect
      may exist. CONCLUSION: Combined with the results of previous studies, the current
      case study indicates that there is evidence suggesting that the RBR reading
      strategy in Chinese pure alexia is of limited benefit, a result that appears
      fundamentally different from the LBL reading strategy.

PMID- 25068673
TI  - Nephroprotective potential of Bacopa monniera on hypercholesterolemia induced
      nephropathy via the NO signaling pathway.
AB  - CONTEXT: Bacopa monniera L. (Scrophulariaceae) is used as a traditional medicine
      in India for various ailments such as epilepsy, mental disorders, and also as a
      cardio-tonic. However, its nephroprotective role is still unknown. OBJECTIVE: The
      present study assesses the modulatory impact of the alcoholic (ethanol) extract
      of Bacopa monniera (AEBM) on renal oxido-lipidemic stress in hypercholesterolemic
      rats. MATERIALS AND METHODS: B. monniera (1 kg) was extracted with 90% ethanol,
      filtered, and dried (52 g). Group-I rats as control, Group-II rats fed with a
      hypercholesterolemic diet (HCD) for 45 d [4% cholesterol and 1% cholic acid],
      Group-III rats fed with HCD for 45 d + AEBM (40 mg/kg, body weight) for last 30
      d, and Group-IV AEBM alone rats. Blood and kidney were removed to analyze lipid,
      antioxidant status, and histological analysis. RESULT: The levels of total
      cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal functional
      parameters (urea, creatinine, and uric acid), and lipid peroxidation (LPO)
      products were significantly attenuated (p < 0.01) in AEBM-treated
      hypercholesterolemic rats. Activities of both enzymic (superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase
      (GST), and glutathione reductase (GR)) and non-enzymic antioxidant (GSH, Vit-C,
      and Vit-E) were significantly increased (p < 0.01), on supplementation with AEBM.
      Administration with AEBM the mRNA levels of eNOS and iNOS genes was significantly
      up-regulated and down-regulated (p < 0.01). Histomorphological observations also
      evidenced that AEBM effectively protects the kidney from hypercholesterolemia
      mediated oxido-lipidemic damage. DISCUSSION AND CONCLUSION: From this study, we
      hypothesized that AEBM can act as renoprotective agent by attenuating the renal
      oxido-lipidemic stress via regulating NOS level and thereby protects the nephron
      in hypercholesterolemic rats.

PMID- 25068674
TI  - A Scutellaria baicalensis radix water extract inhibits morphine-induced
      conditioned place preference.
AB  - CONTEXT: Scutellaria baicalensis Georgi (Lamiaceae) has been used as a
      traditional herbal preparation for the treatment of neuropsychiatric disorders in
      Asian countries for centuries. OBJECTIVE: To evaluate the effects of S.
      baicalensis on morphine-induced drug dependence in rats. MATERIALS AND METHODS:
      In order to evaluate the effect of S. baicalensis and baicalin on morphine
      induced dependence-like behavior, a water extract of S. baicalensis [500 mg/kg,
      intraperitoneally (i.p.)] or baicalin (50 mg/kg, i.p., a flavonoid found in S.
      baicalensis) was administered prior to morphine injection [5 and 2.5 mg/kg,
      respectively, subcutaneously (s.c.)] to rats for 8 and 4 d, respectively.
      Morphine-induced conditioned place preference was assessed by measuring the time
      spent in a drug-paired chamber. The effect of S. baicalensis on dopamine receptor
      supersensitivity (locomotor activity) and dopamine agonist-induced climbing
      behavior due to a single apomorphine treatment (2 mg/kg, s.c.) was also measured.
      RESULTS: At 50 mg/kg, a water extract of S. baicalensis decreased morphine (5
      mg/kg)-induced conditioned place preference by 86% in rats. Apomorphine (2 mg/kg)
      induced locomotor activity (dopamine receptor supersensitivity) in rats and
      climbing behavior in mice were attenuated after pretreatment with 500 mg/kg of S.
      baicalensis water extract by 41% and 56%, respectively. In addition, baicalin
      reduced morphine-induced conditioned places preference by 86% in rats at 50
      mg/kg. DISCUSSION AND CONCLUSION: These results suggest that S. baicalensis can
      ameliorate drug addiction-related behavior through functional regulation of
      dopamine receptors.

PMID- 25068675
TI  - Muntingia calabura: a review of its traditional uses, chemical properties, and
      pharmacological observations.
AB  - CONTEXT: Different parts of Muntingia calabura L. (Elaeocarpaceae), or "kerukup
      siam" in Malay, have been reported to possess medicinal value, supported by a
      number of scientific studies. OBJECTIVE: To gather all information related to the
      ethnomedicinal uses, phytochemical compositions, and pharmacological activities
      of M. calabura and present them as a comprehensive and systematic review article.
      MATERIALS AND METHODS: Literature has been retrieved from a number of databases
      (e.g., Pubmed, Science Direct, Springer Link, etc.). General web searches were
      also carried out using Google and Yahoo search engines by applying some related
      search terms (e.g., Muntingia calabura, phytochemical, pharmacological, extract,
      and traditional uses). The articles related to agriculture, ecology, and
      synthetic work and those using languages other than English or Malay have been
      excluded. The bibliographies of papers relating to the review subject were also
      searched for further relevant references. RESULTS AND DISCUSSION: The literature
      search conducted using the above-mentioned Internet search engines only lead to
      the identification of 36 journals published as early as 1987. From the articles
      reviewed, M. calabura possessed various pharmacological activities (e.g.,
      cytotoxic, antinociceptive, antiulcer, anti-inflammatory), which supported the
      folklore claims and could be attributed to its phytoconstituents. CONCLUSION:
      Muntingia calabura possesses remarkable medicinal value, which warrants further
      and in-depth studies. Therefore, this review paper is presented to help guide
      researchers to plan their future studies related to this plant in the hope of
      isolating potential leads for future drug development.

PMID- 25068676
TI  - The effect of pedometer use on physical activity and body weight in obese women.
AB  - Physical activity and healthy eating are of the utmost importance in treatment of
      obesity. However obese generally tend to have a sedentary lifestyle. Walking is a
      form of physical activity that is both simple and can be performed by everyone,
      but it requires an objective measurement. Number of steps taken during tracking
      can be recorded with the pedometer, a device used to measure the level of
      physical activity. We aimed to investigate whether or not using pedometers as a
      motivational technique to increase the level of physical activity in obese women
      has an impact on weight loss. Eighty-four obese women who are similar age
      referring to Ataturk University Faculty of Medicine Healthy Living Clinic, Turkey
      were randomly divided into two groups. Intervention group were given pedometers,
      and control group were prescribed similar diet and physical activity with a three
      month follow-up plan without pedometers. Mean weight in pedometer group initially
      was 88.9 +/- 8.4 kg, which decreased to 80.2 +/- 8.7 kg after the programme. Mean
      weight in control group was 86.1 +/- 9.2 kg at the beginning, and it decreased to
      84.7 +/- 8.8 kg after three months. It was observed in pedometer group that the
      mean number of steps 8817 +/- 2725 steps/day at the beginning increased to mean
      9716 +/- 2811 steps/day at the end of the study. Weight, body mass index, body
      fat percentage and waist circumference measurements decreased more greatly in the
      pedometer when compared to the control group (p < 0.001). Pedometers may be
      recommended to obese patients to monitor and increase the level of physical
      activity and to promote weight loss. 

PMID- 25068677
TI  - What we can learn from the norms of one-particle density matrices, and what we
      can't: some results for interstate properties in model singlet fission systems.
AB  - The utility of the norms of one-particle density matrices, ?gamma?, for
      understanding the trends in electronic properties is discussed. Using several
      model systems that are relevant in the context of singlet fission (butadiene,
      octatetraene, and ethylene dimer), the dependence of interstate properties (such
      as transition dipole moments and nonadiabatic couplings, NACs) on molecular
      geometries is investigated. ?gamma? contains the principal information about the
      changes in electronic states involved, such as varying degree of one-electron
      character of the transition; thus, it captures leading trends in one-electron
      interstate properties (i.e., when ?gamma? is small, the respective interstate
      matrix elements are also small). However, finer variations in properties that
      arise due to the dependence of the matrix elements of the respective operators
      may not be reproduced. Analysis of NACs in ethylene dimer reveals that
      intermolecular components of NACs follow the trends in ?gamma? well, as they are
      determined primarily by the characters of the two wave functions; however,
      intramolecular components depend on the relative orientation of the two moieties
      via the dependence in the derivative of the electron-nuclear Coulomb operator.
      Therefore, intramolecular NACs may exhibit large variations even when the changes
      in ?gamma? are small. We observe large NACs at perfectly stacked geometry;
      however, larger values (by a factor of 1.6) are observed at slip-stacked (along
      the long axis) geometries. Larger values of NACs at slip-stacked configurations
      are due to the breaking of symmetry of the local environment of the heavy atoms
      and not due to the wave function composition. We found that the variations in
      ?gamma? for ethylene dimer are due to a varying admixture of the charge-resonance
      configurations in the S1 state, whereas the (1)ME state retains its pure
      multiexciton character. 

PMID- 25068678
TI  - How torsional effects cause attack at sterically crowded concave faces of
      bicyclic alkenes.
AB  - Cycloadditions of 1,3-dipoles and related species to a cis
      oxabicyclo[3.3.0]octenone occur on the more sterically crowded concave face.
      These cycloadditions were studied experimentally by Gais and co-workers in 1998
      (Eur. J. Org. Chem. 1998, 257-273) and have now been studied computationally with
      density functional theory (DFT). Transition states have been computed for various
      types of (3 + 2) cycloadditions, including diazomethane 1,3-dipolar
      cycloadditions, a thermally promoted methylenecyclopropane acetal cycloaddition,
      and a Pd-catalyzed cycloaddition of methylenecyclopropane to an
      oxabicyclo[3.3.0]octenone. The concave stereoselectivities arise from alkene
      predistortion that leads to torsional steering in the transition states. 

PMID- 25068679
TI  - IgG4-related disease: a rheumatologist's perspective.
AB  - OBJECTIVES: Given that the clinical features of several IgG4-related diseases
      (IgG4-RD) can mimic those of autoimmune disorders, the aim of this study was to
      find possible distinguishing characteristics that would help us identify such
      cases from the pool of patients in a rheumatology clinic. METHODS: From our
      clinic's medical records, we identified patients who fulfilled the recently
      published diagnostic criteria for IgG4-RD. We recorded their presenting features,
      co-morbid conditions, laboratory, radiologic and histologic findings as well as
      their treatment and outcome. RESULTS: We identified 11 cases of IgG4-RD: 4 cases
      of IgG4-related autoimmune pancreatitis (AIP), 5 cases of IgG4-related
      retroperitoneal fibrosis (RPF)/ periaortitis, 2 cases of IgG4-related
      sialadenitis and one of IgG4-related interstitial nephritis. 5 out of the 11
      patients had been diagnosed with an autoimmune disease, namely rheumatoid
      arthritis (RA), Sjogren's syndrome (SS) and antiphospholipid syndrome (APS). 3
      out of 11 patients were subsequently diagnosed with neoplastic disorders. All
      patients with IgG4-related AIP had raised CRP levels at presentation. Presenting
      features of RPF/periaortitis patients were constitutional symptoms, abnormal
      renal function, hypertension and back pain. Patients with IgG4-related
      sialadenitis had clinical features mimicking SS. The majority of patients had a
      favourable response to steroids. CONCLUSIONS: We present common IgG4-RD
      presentations in the setting of a rheumatology clinic. Increased awareness may
      avoid delay in diagnosis.

PMID- 25068680
TI  - Counterion-assisted cation transport in a biological calcium channel.
AB  - How ions pass through the lumen of an ion channel is a key question underlying
      cellular communication. The effects of water and pore-lining residues (channel
      design) have been extensively explored. However, the role of counterions is less
      well understood. The pore subunit of the calcium release-activated calcium
      channel, Orai, provides a useful model to explore the effect of anions on the
      permeation of cations. Herein, we employ computer simulations molecular dynamics
      (MD) to explore ion permeation through the V174A Orai mutant, a constitutively
      open pore, in a phospholipid membrane hydrated by a 150 mM NaCl solution. When an
      external voltage is applied in the MD simulations, it induces only a moderate
      conformational change to the channel, which facilitates the passage of ions.
      Infrequent sodium permeation is observed on the microsecond time scale, which is
      consistent with experiment. In contrast, the chloride counterions exhibit higher
      mobility in the channel and are actively involved in sodium transport. The anion
      assisted cation permeation identified here likely highlights a more general
      functional role for counterions, especially in ion channels with medium pore
      size. Experiments with a variety of counterions might further illuminate the
      nature of their active role. 

PMID- 25068681
TI  - Efficient copper-catalyzed trifluoromethylation of aromatic and heteroaromatic
      iodides: the beneficial anchoring effect of borates.
AB  - Efficient copper-catalyzed trifluoromethylation of aromatic iodides was achieved
      with TMSCF3 in the presence of trimethylborate. The Lewis acid was used to anchor
      the in situ generated trifluoromethyl anion and suppress its rapid decomposition.
      Broad applicability of the new trifluoromethylating reaction was demonstrated in
      the functionalization of different aromatic and heteroaromatic iodides. 

PMID- 25068682
TI  - Measurement and evaluation of isotypes of anti-citrullinated fibrinogen and anti
      citrullinated alpha-enolase antibodies in juvenile idiopathic arthritis.
AB  - OBJECTIVES: Our objective was to evaluate sera from juvenile idiopathic arthritis
      (JIA) patients to investigate the presence of isotypes (IgA, IgG, IgM) of anti
      citrullinated fibrinogen and anti-alpha-enolase antibodies and their association
      with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)
      antibody isotypes. METHODS: Sera were obtained from 89 JIA patients and were
      measured for isotypes (IgA, IgM) of anti-citrullinated and native fibrinogen and
      anti-alpha-enolase antibodies by enzyme-linked immunosorbent assay. Results were
      compared to anti-CCP antibody isotypes and RF isotypes, in addition to previously
      measured IgG anti-citrullinated fibrinogen and alpha-enolase antibodies. RESULTS:
      IgA anti-citrullinated fibrinogen antibodies were positive in 20 JIA patients and
      IgM in 11 JIA patients. Two IgM RF-positive polyarthritis patients were positive
      for all 3 isotypes of anti-citrullinated fibrinogen antibodies. IgA anti
      citrullinated alpha-enolase antibodies were positive in 7 JIA patients and IgM in
      9 JIA patients. IgA and IgG anti-citrullinated fibrinogen antibodies were
      commonly found in JIA patients positive for IgG anti-CCP antibodies and IgM RF.
      IgG anti-CCP antibodies and IgM RF levels were significantly higher in JIA
      patients with 3 or more anti-citrullinated autoantibody isotypes present.
      CONCLUSIONS: We have shown that isotypes of anti-citrullinated fibrinogen and
      alpha-enolase can be found in the serum of children with JIA of all onset types.
      Citrullinated autoantibody isotype diversity may indicate a more severe disease
      course in JIA patients.

PMID- 25068683
TI  - Functional domain analysis of the cell division inhibitor EzrA.
AB  - The precise spatial and temporal control of bacterial cell division is achieved
      through the balanced actions of factors that inhibit assembly of the tubulin-like
      protein FtsZ at aberrant subcellular locations or promote its assembly at the
      future sites of division. In Bacillus subtilis, the membrane anchored cell
      division protein EzrA, interacts directly with FtsZ to prevent aberrant FtsZ
      assembly at cell poles and contributes to the inherently dynamic nature of the
      cytokinetic ring. Recent work suggests EzrA also serves as a scaffolding protein
      to coordinate lateral growth with cell wall biosynthesis through interactions
      with a host of proteins, a finding consistent with EzrA's four extensive coiled
      coil domains. In a previous study we identified a conserved patch of residues
      near EzrA's C-terminus (the QNR motif) that are critical for maintenance of a
      dynamic cytokinetic ring, but dispensable for EzrA-mediated inhibition of FtsZ
      assembly at cell poles. In an extension of this work, here we report that EzrA's
      two C-terminal coiled-coils function in concert with the QNR motif to mediate
      interactions with FtsZ and maintain the dynamic nature of the cytokinetic ring.
      In contrast, EzrA's two N-terminal coiled-coils are dispensable for interaction
      between EzrA and FtsZ in vitro and in vivo, but required for EzrA mediated
      inhibition of FtsZ assembly at cell poles. Finally, chimeric analysis indicates
      that EzrA's transmembrane anchor plays a generic role: concentrating EzrA at the
      plasma membrane where presumably it can most effectively modulate FtsZ assembly. 

PMID- 25068684
TI  - A Eu(III) tetrakis(beta-diketonate) dimeric complex: photophysical properties,
      structural elucidation by Sparkle/AM1 calculations, and doping into PMMA films
      and nanowires.
AB  - Reaction of Ln(III) with a tetrakis(diketone) ligand H4L [1,1'-(4,4'-(2,2-bis((4
      (4,4,4-trifluoro-3-oxobutanoyl) phenoxy)methyl)propane-1,3-diyl)bis(oxy)bis(4,1
      phenylene))bis(4,4,4-trifluorobutane-1,3-dione)] gives new podates which,
      according to mass spectral data and Sparkle/AM1 calculations, can be described as
      dimers, (NBu4[LnL])2 (Ln = Eu, Tb, Gd:Eu), in both solid-state and
      dimethylformamide (DMF) solution. The photophysical properties of the Eu(III)
      podate are compared with those of the mononuclear diketonate (NBu4[Eu(BTFA)4],
      BTFA = benzoyltrifluoroacetonate), the crystal structure of which is also
      reported. The new Eu(III) dimeric complex displays bright red luminescence upon
      irradiation at the ligand-centered band in the range of 250-400 nm, irrespective
      of the medium. The emission quantum yields and the luminescence lifetimes of
      (NBu4[EuL])2 (solid state: 51% +/- 8% and 710 +/- 2 MUs; DMF: 31% +/- 5% and 717
      +/- 1 MUs) at room temperature are comparable to those obtained for
      NBu4[Eu(BTFA)4] (solid state: 60 +/- 9% and 730 +/- 5 MUs; DMF: 30 +/- 5% and 636
      +/- 1 MUs). Sparkle/AM1 calculations were utilized for predicting the ground
      state geometries of the Eu(III) dimer. Theoretical Judd-Ofelt and
      photoluminescence parameters, including quantum yields, predicted from this model
      are in good agreement with the experimental values, proving the efficiency of
      this theoretical approach implemented in the LUMPAC software
      (http://lumpac.pro.br). The kinetic scheme for modeling energy transfer processes
      show that the main donor state is the ligand triplet state and that energy
      transfer occurs on both the (5)D1 (44.2%) and (5)D0 (55.8%) levels. Furthermore,
      the newly obtained Eu(III) complex was doped into a PMMA matrix to form highly
      luminescent films and one-dimensional nanowires having emission quantum yield as
      high as 67%-69% (doping concentration = 4% by weight); these materials display
      bright red luminescence even under sunlight, so that interesting photonic
      applications can be foreseen.

PMID- 25068685
TI  - [Physician-assisted suicide and advance care planning--ethical considerations on
      the autonomy of dementia patients at their end of life].
AB  - Physician-assisted suicide (PAS), which is currently the subject of intense and
      controversial discussion in medical ethics, is barely discussed in psychiatry,
      albeit there are already dementia patients in Germany and other European
      countries who end their own lives with the assistance of physicians. Based on the
      finding that patients who ask for medical assistance in suicide often have in
      mind the loss of their mental capacity, we submit PAS to an ethical analysis and
      put it into a broader context of patient autonomy at the end of life. In doing
      so, we point to advance care planning, through which the patient autonomy of the
      person concerned can be supported as well as respected in later stages of the
      disease. If patients adhere to their autonomous wish for PAS, physicians find
      themselves in an ethical dilemma. A further tabooing of the topic, however, does
      not provide a solution; rather, an open societal and professional ethical
      discussion and regulation are essential.

PMID- 25068686
TI  - [Representations of Care of Migrants from the former Soviet Union with Alcohol or
      Drug Problems in Germany].
AB  - OBJECTIVE: Which representations of care can be found in migrants with alcohol or
      drug problems from the former Soviet Union? How do they correspond with views in
      the care system? METHODS: Episodic interviews with 46 migrants, expert interviews
      with 33 service providers; analysis with thematic coding. RESULTS: For migrants
      and experts holistic care is important, which include spiritual-religious
      components but are also control-oriented. CONCLUSION: The cultural specificity of
      migrants' care representations should be acknowledged by the health care system
      much more.

PMID- 25068687
TI  - [Long-Term Tendencies in the Use of Seclusion and Restraint in Five Psychiatric
      Hospitals in Germany].
AB  - OBJECTIVE: To evaluate multiple efforts of the last decade to reduce the use of
      coercive measures in psychiatric hospitals. METHOD: A working group for the
      prevention of violence and coercion in psychiatric hospitals has compared several
      outcome indicators since the year 2000 and repeatedly has provided evidence-based
      recommendations for clinical practice. We present data from those 5 hospitals
      with complete data sets recorded by an identical method over 9 years. RESULTS:
      The percentage of admissions exposed to any kind of coercive measure decreased
      from 8.2 % in 2004 to 6.2 % in 2012. The standard deviation of outcomes between
      hospitals decreased by 20 %. Changes in the duration of measures were mostly
      insignificant. CONCLUSIONS: Measures to reduce the use of coercion are effective
      in clinical practice, but to less extent than in clinical studies. A ban on all
      forced and non-consensual medical interventions, as being stipulated by the UN
      Special Rapporteur on Torture, has so far not materialized in the participating
      psychiatric institutions.

PMID- 25068688
TI  - [Weight Related Stigmatisation of Obese Individuals in Somatic and Mental Health
      Care - are there Differences?].
AB  - OBJECTIVE: Stigmatization of obese patients by health care professionals
      represents a significant barrier to seek care. The study aims to identify weight
      related stigmatizing attitudes of mental and somatic health care professionals.
      METHODS: The data base was derived from a survey of 773 health care professionals
      using a vignette-based approach. Stigmatizing attitudes were assessed with the
      Fat Phobia Scale. RESULTS: Health care professionals in the somatic and mental
      health field stigmatize overweight individuals. Stigmatizing attitudes were
      associated with the belief in the lack of willpower of obese people and an
      increased perceived workload caused by overweight patients. CONCLUSIONS: The
      stigmatization of obese people needs to be addressed and mentally ill patients
      seem to be an especially vulnerable group due to double stigma.

PMID- 25068689
TI  - [Clinical ethics in psychiatry: state of the art].
AB  - AIM: Overview on Clinical Ethics Consultation in Psychiatry. METHOD: Systematic
      literature search in data bases (PubMed, Web of Knowledge, SpringerLink,
      PubPsych, PsychSpider und PsycINFO) against the background of practical
      experiences with pilot model of implementation of Ethics Consultation in one
      psychiatric university hospital. RESULTS: Reports on Ethics Consultation in
      Psychiatry were published only sporadically. This is contrasted by recent
      experiences showing considerable needs for ethics support in Child and Adolescent
      Psychiatry, Adult as well as Forensic Psychiatry. DISCUSSION: This somewhat
      "late" development of Ethics Consultation in Psychiatry (compared with somatic
      medicine) might have structural reasons (lacking resources), be related to strong
      compensatory competencies of psychiatric staff, esp. regarding communication or
      legal knowledge, but could also relate to an under-estimation ("under
      diagnostic") of ethical problems in psychiatric patient care - both, in the eyes
      of psychiatric insiders, as well as seen from the outside. CONCLUSIONS: Needs for
      model projects and accompanying research on Ethics Consultation in Psychiatry.
      Proved in practice: patient- as well as team-oriented ethics support.

PMID- 25068690
TI  - Safety and efficacy of drug-induced sleep endoscopy using a probability ramp
      propofol infusion system in patients with severe obstructive sleep apnea.
AB  - BACKGROUND: Drug-induced sleep endoscopy (DISE) uses sedative-hypnotics to induce
      moderate obstruction in sleep apnea patients, thereby facilitating anatomic
      assessment of obstructive physiology. Implementation of DISE with propofol
      requires a dosing strategy that reliably and efficiently produces obstruction
      while minimizing oxygen desaturation. METHODS: The surgeon in a prospective study
      of transoral robotic resection of the tongue base enrolled 97 patients with
      obstructive sleep apnea confirmed by polysomnography who failed continuous
      positive airway pressure. All patients were screened by DISE. Propofol dose was
      determined using custom software written in MATLAB, which has been previously
      described. Studies were performed in an operating room with standard monitors and
      resuscitation equipment. No topical anesthesia was used, and no IV drugs other
      than propofol were used. All patients received 2 L/min supplemental oxygen via a
      nasal cannula placed in the mouth. After initiation of propofol sedation, a
      pediatric bronchoscope was positioned via the naris to observe the velopharynx.
      The sedation sequence was continued until the clinical end point of obstruction
      onset was noted. Observation of the pharynx was performed for a sufficient period
      to obtain images of the anatomic site(s) of obstruction. The infusion was then
      terminated. Statistical analysis was performed with MATLAB (MathWorks, version
      2012b). Comparison of saturation nadirs between DISE and subject sleep studies
      was performed with both the paired and unpaired Student t test. RESULTS: The
      subject population was characterized by a median body mass index of 32.1
      (interquartile range [IQR] 6.8) kg/m and apnea-hypopnea index of 48 (IQR 32). All
      patients demonstrated obstruction within the design variables. Obstruction was
      observed after 236 (+/-57.9) seconds at an estimated effect-site concentration of
      4.2 +/- 1.3 mcg/mL. The median saturation nadir during DISE was significantly
      higher (91.4% (IQR 5.1)) than that during standard sleep studies (81.0% [IQR
      11.2], P < 0.0001). Ninety-five percent confidence intervals for correlations
      between DISE saturation nadir and body mass index, age, apnea-hypopnea index, or
      administered propofol dose included zero in all cases. CONCLUSIONS: A propofol
      infusion strategy that requires limited experience with propofol dose selection
      and only 1 pump dosing change reliably produced airway obstruction in patients
      with severe sleep apnea. Clinical obstruction was achieved faster than target
      controlled infusion-based systems for similar procedures reported in the
      literature. The observed degree of oxygen desaturation in the model system was
      within a clinically acceptable range.

PMID- 25068691
TI  - Glucose may attenuate isoflurane-induced caspase-3 activation in H4 human
      neuroglioma cells.
AB  - BACKGROUND: The commonly used inhaled anesthetic isoflurane has been shown to
      induce caspase-3 activation. However, the underlying mechanism(s) and targeted
      intervention(s) remain largely to be determined. Isoflurane may induce caspase-3
      activation via causing accumulation of reactive oxygen species (ROS),
      mitochondrial dysfunction, and reduction in adenosine triphosphate (ATP) levels.
      Therefore, we performed a hypothesis-generation study to determine whether
      glucose could attenuate isoflurane-induced caspase-3 activation, ROS
      accumulation, mitochondrial dysfunction, and ATP reduction in cultured cells.
      METHODS: H4 human neuroglioma cells (H4 cells) were treated with 2% isoflurane or
      the control condition plus saline or 50 mM glucose for 6 or 3 hours. Caspase-3
      activation, cell viability, levels of ROS and ATP, and mitochondrial membrane
      potential were determined at the end of the experiments by Western blot analysis
      and fluorescence assay. RESULTS: We found that the glucose treatment might
      attenuate isoflurane-induced caspase-3 activation and reduction of cell viability
      in H4 cells. Moreover, the glucose treatment mitigated the isoflurane-induced
      increase in ROS levels and reduction in ATP levels in H4 cells. Unexpectedly, we
      observed that the glucose treatment might not inhibit the isoflurane-induced
      decrease in mitochondrial membrane potential in H4 cells. CONCLUSIONS: Pending
      further studies, these results suggested that glucose might attenuate isoflurane
      induced caspase-3 activation through a mitochondria-independent reduction in ROS
      levels and enhancement in ATP levels. These findings have established a system
      and suggest that it is worth performing more research to further investigate
      whether glucose can attenuate anesthesia neurotoxicity.

PMID- 25068692
TI  - Mathematical model for the contribution of individual organs to non-zero y
      intercepts in single and multi-compartment linear models of whole-body energy
      expenditure.
AB  - Mathematical models for the dependence of energy expenditure (EE) on body mass
      and composition are essential tools in metabolic phenotyping. EE scales over
      broad ranges of body mass as a non-linear allometric function. When considered
      within restricted ranges of body mass, however, allometric EE curves exhibit
      'local linearity.' Indeed, modern EE analysis makes extensive use of linear
      models. Such models typically involve one or two body mass compartments (e.g.,
      fat free mass and fat mass). Importantly, linear EE models typically involve a
      non-zero (usually positive) y-intercept term of uncertain origin, a recurring
      theme in discussions of EE analysis and a source of confounding in traditional
      ratio-based EE normalization. Emerging linear model approaches quantify whole
      body resting EE (REE) in terms of individual organ masses (e.g., liver, kidneys,
      heart, brain). Proponents of individual organ REE modeling hypothesize that multi
      organ linear models may eliminate non-zero y-intercepts. This could have
      advantages in adjusting REE for body mass and composition. Studies reveal that
      individual organ REE is an allometric function of total body mass. I exploit
      first-order Taylor linearization of individual organ REEs to model the manner in
      which individual organs contribute to whole-body REE and to the non-zero y
      intercept in linear REE models. The model predicts that REE analysis at the
      individual organ-tissue level will not eliminate intercept terms. I demonstrate
      that the parameters of a linear EE equation can be transformed into the
      parameters of the underlying 'latent' allometric equation. This permits estimates
      of the allometric scaling of EE in a diverse variety of physiological states that
      are not represented in the allometric EE literature but are well represented by
      published linear EE analyses. 

PMID- 25068693
TI  - A fibril-like assembly of oligomers of a peptide derived from beta-amyloid.
AB  - A macrocyclic beta-sheet peptide containing two nonapeptide segments based on
      Abeta(15-23) (QKLVFFAED) forms fibril-like assemblies of oligomers in the solid
      state. The X-ray crystallographic structure of macrocyclic beta-sheet peptide 3
      was determined at 1.75 A resolution. The macrocycle forms hydrogen-bonded dimers,
      which further assemble along the fibril axis in a fashion resembling a
      herringbone pattern. The extended beta-sheet comprising the dimers is laminated
      against a second layer of dimers through hydrophobic interactions to form a
      fibril-like assembly that runs the length of the crystal lattice. The second
      layer is offset by one monomer subunit, so that the fibril-like assembly is
      composed of partially overlapping dimers, rather than discrete tetramers. In
      aqueous solution, macrocyclic beta-sheet 3 and homologues 4 and 5 form discrete
      tetramers, rather than extended fibril-like assemblies. The fibril-like
      assemblies of oligomers formed in the solid state by macrocyclic beta-sheet 3
      represent a new mode of supramolecular assembly not previously observed for the
      amyloidogenic central region of Abeta. The structures observed at atomic
      resolution for this peptide model system may offer insights into the structures
      of oligomers and oligomer assemblies formed by full-length Abeta and may provide
      a window into the propagation and replication of amyloid oligomers.

PMID- 25068694
TI  - Golgi fragmentation and sphingomyelin transport to Chlamydia trachomatis during
      penicillin-induced persistence do not depend on the cytosolic presence of the
      chlamydial protease CPAF.
AB  - Chlamydia grows inside a cytosolic vacuole (the inclusion) that is supplied with
      nutrients by the host through vesicular and non-vesicular transport. It is
      unclear in many respects how Chlamydia organizes this transport. One model posits
      that the Chlamydia-induced fragmentation of the Golgi-apparatus is required for
      normal transport processes to the inclusion and for chlamydial development, and
      the chlamydial protease CPAF has been controversially implicated in Golgi
      fragmentation. We here use a model of penicillin-induced persistence of infection
      with Chlamydia trachomatis to test this link. Under penicillin-treatment the
      inclusion grew in size for the first 24 h but after that growth was severely
      reduced. Penicillin did not reduce the number of infected cells with fragmented
      Golgi-apparatus, and normal Golgi-fragmentation was found in a CPAF-deficient
      mutant. Surprisingly, sphingomyelin transport into the inclusion and into the
      bacteria, as measured by fluorescence accumulation upon addition of labelled
      ceramide, was not reduced during penicillin-treatment. Thus, both Golgi
      fragmentation and transport of sphingomyelin to C. trachomatis still occurred in
      this model of persistence. The portion of cells in which CPAF was detected in the
      cytosol, either by immunofluorescence or by immune-electron microscopy, was
      drastically reduced in cells cultured in the presence of penicillin. These data
      argue against an essential role of cytosolic CPAF for Golgi-fragmentation or for
      sphingomyelin transport in chlamydial infection. 

PMID- 25068695
TI  - What we can't see? Understanding the representations and meanings of UAI,
      barebacking, and semen exchange in gay male pornography.
AB  - Since the late 1990s, the use of condoms within gay male pornography has been on
      the wane. Moving from a niche category into more mainstream forms of commercial
      pornography, unprotected anal sex has become a dominant theme within this sphere
      of gay male sexual representation. However, while the definition of what
      constitutes bareback pornography may at first sight appear unproblematic, this
      article argues that meanings and understandings of unprotected anal intercourse
      (UAI) are not constant across all genres of gay male pornography. Using textual
      analysis and focus group methods, the authors demonstrate how subcultural
      understandings of UAI are dependent on a variety of textual factors. These
      include the age, body type, and racial identities of the performers; the setting,
      context, and mise-en-scene of the pornographic scene; and the deployment of power
      relations between the insertive and receptive partners. The article concludes by
      suggesting that the recognition of the diverse representations of "barebacking"
      found in contemporary gay male pornography should influence the ways in which
      health promotion strategies address discussions of UAI and bareback pornography. 

PMID- 25068696
TI  - Effects of action video game training on visual working memory.
AB  - The ability to hold visual information in mind over a brief delay is critical for
      acquiring information and navigating a complex visual world. Despite the
      ubiquitous nature of visual working memory (VWM) in our everyday lives, this
      system is fundamentally limited in capacity. Therefore, the potential to improve
      VWM through training is a growing area of research. An emerging body of
      literature suggests that extensive experience playing action video games yields a
      myriad of perceptual and attentional benefits. Several lines of converging work
      suggest that action video game play may influence VWM as well. The current study
      utilized a training paradigm to examine whether action video games cause
      improvements to the quantity and/or the quality of information stored in VWM. The
      results suggest that VWM capacity, as measured by a change detection task, is
      increased after action video game training, as compared with training on a
      control game, and that some improvement to VWM precision occurs with action game
      training as well. However, these findings do not appear to extend to a complex
      span measure of VWM, which is often thought to tap into higher-order executive
      skills. The VWM improvements seen in individuals trained on an action video game
      cannot be accounted for by differences in motivation or engagement, differential
      expectations, or baseline differences in demographics as compared with the
      control group used. In sum, action video game training represents a potentially
      unique and engaging platform by which this severely capacity-limited VWM system
      might be enhanced.

PMID- 25068697
TI  - Control of response timing occurs during the simple reaction time interval but on
      line for choice reaction time.
AB  - The preparation of multiple element movements has been examined for decades, with
      no clear explanation offered for the disparate results observed. Results from 2
      experiments are presented and, in conjunction with previous results, a
      theoretical interpretation is offered regarding the preparatory processes that
      occur before, during and after the reaction time (RT) interval for multiple
      element movements during both simple and choice RT paradigms. In Experiment 1,
      number of elements and timing complexity were manipulated in a simple RT key
      press task, using a startling acoustic stimulus to probe advance preparation.
      Both startle and nonstartle RT increased with number of movement elements and for
      a movement with increased timing complexity, providing evidence that the control
      of response timing occurs during the RT interval. In Experiment 2, the production
      of key-press movements of varying number of elements was compared in a simple
      versus choice RT paradigm. Results indicated that simple RT was affected by the
      number of elements, yet choice RT was not. Additionally, choice RT trials showed
      significantly longer interresponse intervals compared with those observed in
      simple RT trials, providing evidence for online processing in choice RT. The
      results of both studies, together with previous findings, suggest that planning
      of the timing of the onsets of the elements is prepared during simple RT, whereas
      planning of other aspects of the sequence of elements seems to occur in the
      foreperiod prior to the "go" signal. Conversely, in the choice RT paradigm,
      timing seems to be controlled online. This explanation may bring closure on
      difficulties encountered in over 50 years of research examining response
      preparation for complex movements.

PMID- 25068698
TI  - Incidental sequence learning in a motion coherence discrimination task: How
      response learning affects perception.
AB  - The serial reaction time task (SRTT) is a standard task used to investigate
      incidental sequence learning. Whereas incidental learning of motor sequences is
      well-established, few and disputed results support learning of perceptual
      sequences. Here we adapt a motion coherence discrimination task (Newsome & Pare,
      1988) to the sequence learning paradigm. The new task has 2 advantages: (a) the
      stimulus is presented at fixation, thereby obviating overt eye movements, and (b)
      by varying coherence a perceptual threshold measure is available in addition to
      the performance measure of RT. Results from 3 experiments show that action
      relevance of the sequence is necessary for sequence learning to occur, that the
      amount of sequence knowledge varies with the ease of encoding the motor sequence,
      and that sequence knowledge, once acquired, has the ability to modify perceptual
      thresholds.

PMID- 25068699
TI  - Coexistence of granular cell tumor and invasive ductal breast cancer in
      contralateral breasts: a case report.
AB  - Granular cell tumor (GCT) is a benign tumor of the breast that can mimic, on
      breast imaging, invasive carcinomas. Biological evolution of mammary GCT is
      unknown, especially if it is associated with an invasive carcinoma in the same or
      contralateral breast. This report details the morphological features of these
      synchronous lesions highlighting their biological characteristics and suggesting
      an appropriate follow up. 

PMID- 25068701
TI  - Possible protective effect of membrane lipid rafts against interleukin-1beta
      mediated anti-proliferative effect in INS-1 cells.
AB  - We recently reported that pancreatic islets from pre-diabetic rats undergo an
      inflammatory process in which IL-1beta takes part and controls beta-cell
      function. In the present study, using the INS-1 rat pancreatic beta-cell line, we
      investigated the potential involvement of membrane-associated cholesterol
      enriched lipid rafts in IL-1beta signaling and biological effects on insulin
      secretion, beta-cell proliferation and apoptosis. We show that, INS-1 cells
      exposure to increasing concentrations of IL-1beta leads to a progressive
      inhibition of insulin release, an increase in the number of apoptotic cells and a
      dose-dependent decrease in pancreatic beta-cell proliferation. Disruption of
      membrane lipid rafts markedly reduced glucose-stimulated insulin secretion but
      did not affect either cell apoptosis or proliferation rate, demonstrating that
      membrane lipid raft integrity is essential for beta-cell secretory function. In
      the same conditions, IL-1beta treatment of INS-1 cells led to a slight further
      decrease in insulin secretion for low concentrations of the cytokine, and a more
      marked one, similar to that observed in normal cells for higher concentrations.
      These effects occurred together with an increase in iNOS expression and
      surprisingly with an upregulation of tryptophane hydroxylase and protein Kinase C
      in membrane lipid rafts suggesting that compensatory mechanisms develop to
      counteract IL-1beta inhibitory effects. We also demonstrate that disruption of
      membrane lipid rafts did not prevent cytokine-induced cell death recorded after
      exposure to high IL-1beta concentrations. Finally, concerning cell proliferation,
      we bring strong evidence that membrane lipid rafts exert a protective effect
      against IL-1beta anti-proliferative effect, possibly mediated at least partly by
      modifications in ERK and PKB expression/activities. Our results 1) demonstrate
      that IL-1beta deleterious effects do not require a cholesterol-dependent plasma
      membrane compartmentalization of IL-1R1 signaling and 2) confer to membrane lipid
      rafts integrity a possible protective function that deserves to be considered in
      the context of inflammation and especially T2D pathogenesis. 

PMID- 25068703
TI  - Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells
      for efficient CD8(+) T cell response: a comparative study.
AB  - Here we demonstrated the importance of targeting antigens (Ags) to dendritic cell
      (DC) receptors to achieve an efficient cytotoxic T cell response which was
      associated with a strong activation of DC. Pegylated poly(lactic-co-glycolic
      acid) (PLGA) nanoparticles (NPs) were used to encapsulate ovalbumin (OVA) as a
      model Ag. This PLGA complex, together with Toll like receptor (TLR) 3 and 7
      ligands, was then targeted to distinct DC cell-surface molecules. These cell
      surface molecules, including CD40, a TNF-alpha family receptor, DEC-205, a C-type
      lectin receptor and CD11c, an integrin receptor, were targeted by means of
      specific monoclonal antibodies (mAbs) coupled to the NP. The efficiency of these
      different targeting strategies to activate DC and elicit a potent CD8(+) T cell
      response was studied. PLGA-(Ag/TLR3+7L) NP was more efficiently targeted to and
      internalized by DC in vitro compared to the control non-targeted NP. We observed
      a small but significantly improved internalization of CD40-targeted NP compared
      to DEC-205 or CD11c targeted NP. In contrast to non-targeted NP, all targeted NPs
      equally stimulated IL-12 production and expression of co-stimulatory molecules by
      DC, inducing strong proliferation and IFN-y production by T cells in vitro.
      Moreover, subcutaneous vaccination with CD40, DEC-205 and CD11c-targeted NP
      consistently showed higher efficacy than non-targeted NP in stimulating CD8+ T
      cell responses. However, all targeted NP vaccines showed an equal capacity to
      prime cytotoxic CD8+ T cells, which subsequently were able to induce targeted
      cell lysis. In conclusion, delivery of NP-vaccines to DC by targeting via cell
      surface molecules leads to strong enhancement of vaccine potency and induction of
      T cell responses compared to non-specific delivery of NP to DC. 

PMID- 25068704
TI  - Cost minimization using an artificial neural network sleep apnea prediction tool
      for sleep studies.
AB  - RATIONALE: More than a million polysomnograms (PSGs) are performed annually in
      the United States to diagnose obstructive sleep apnea (OSA). Third-party payers
      now advocate a home sleep test (HST), rather than an in-laboratory PSG, as the
      diagnostic study for OSA regardless of clinical probability, but the economic
      benefit of this approach is not known. OBJECTIVES: We determined the diagnostic
      performance of OSA prediction tools including the newly developed OSUNet, based
      on an artificial neural network, and performed a cost-minimization analysis when
      the prediction tools are used to identify patients who should undergo HST.
      METHODS: The OSUNet was trained to predict the presence of OSA in a derivation
      group of patients who underwent an in-laboratory PSG (n = 383). Validation group
      1 consisted of in-laboratory PSG patients (n = 149). The network was trained
      further in 33 patients who underwent HST and then was validated in a separate
      group of 100 HST patients (validation group 2). Likelihood ratios (LRs) were
      compared with two previously published prediction tools. The total costs from the
      use of the three prediction tools and the third-party approach within a clinical
      algorithm were compared. MEASUREMENTS AND MAIN RESULTS: The OSUNet had a higher
      +LR in all groups compared with the STOP-BANG and the modified neck circumference
      (MNC) prediction tools. The +LRs for STOP-BANG, MNC, and OSUNet in validation
      group 1 were 1.1 (1.0-1.2), 1.3 (1.1-1.5), and 2.1 (1.4-3.1); and in validation
      group 2 they were 1.4 (1.1-1.7), 1.7 (1.3-2.2), and 3.4 (1.8-6.1), respectively.
      With an OSA prevalence less than 52%, the use of all three clinical prediction
      tools resulted in cost savings compared with the third-party approach.
      CONCLUSIONS: The routine requirement of an HST to diagnose OSA regardless of
      clinical probability is more costly compared with the use of OSA clinical
      prediction tools that identify patients who should undergo this procedure when
      OSA is expected to be present in less than half of the population. With OSA
      prevalence less than 40%, the OSUNet offers the greatest savings, which are
      substantial when the number of sleep studies done annually is considered.

PMID- 25068705
TI  - Emotional modulation of control dilemmas: the role of positive affect, reward,
      and dopamine in cognitive stability and flexibility.
AB  - Goal-directed action in changing environments requires a dynamic balance between
      complementary control modes, which serve antagonistic adaptive functions (e.g.,
      to shield goals from competing responses and distracting information vs. to
      flexibly switch between goals and behavioral dispositions in response to
      significant changes). Too rigid goal shielding promotes stability but incurs a
      cost in terms of perseveration and reduced flexibility, whereas too weak goal
      shielding promotes flexibility but incurs a cost in terms of increased
      distractibility. While research on cognitive control has long been conducted
      relatively independently from the study of emotion and motivation, it is becoming
      increasingly clear that positive affect and reward play a central role in
      modulating cognitive control. In particular, evidence from the past decade
      suggests that positive affect not only influences the contents of cognitive
      processes, but also modulates the balance between complementary modes of
      cognitive control. In this article we review studies from the past decade that
      examined effects of induced positive affect on the balance between cognitive
      stability and flexibility with a focus on set switching and working memory
      maintenance and updating. Moreover, we review recent evidence indicating that
      task-irrelevant positive affect and performance-contingent rewards exert
      different and sometimes opposite effects on cognitive control modes, suggesting
      dissociations between emotional and motivational effects of positive affect.
      Finally, we critically review evidence for the popular hypothesis that effects of
      positive affect may be mediated by dopaminergic modulations of neural processing
      in prefrontal and striatal brain circuits, and we refine this "dopamine
      hypothesis of positive affect" by specifying distinct mechanisms by which
      dopamine may mediate effects of positive affect and reward on cognitive control.
      We conclude with a discussion of limitations of current research, point to
      central unresolved questions and outline perspective for future research on
      affective and motivational modulations of cognitive control modes. 

PMID- 25068706
TI  - Trend analysis from 1970 to 2008 and model evaluation of EDGARv4 global gridded
      anthropogenic mercury emissions.
AB  - The Emission Database for Global Atmospheric Research (EDGAR) provides a time
      series of man-made emissions of greenhouse gases and short-lived atmospheric
      pollutants from 1970 to 2008. Mercury is included in EDGARv4.tox1, thereby
      enriching the spectrum of multi-pollutant sources in the database. With an
      average annual growth rate of 1.3% since 1970, EDGARv4 estimates that the global
      mercury emissions reached 1,287 tonnes in 2008. Specifically, gaseous elemental
      mercury (GEM) (Hg(0)) accounted for 72% of the global total emissions, while
      gaseous oxidised mercury (GOM) (Hg(2+)) and particle bound mercury (PBM) (Hg-P)
      accounted for only 22% and 6%, respectively. The less reactive form, i.e., Hg(0),
      has a long atmospheric residence time and can be transported long distances from
      the emission sources. The artisanal and small-scale gold production, accounted
      for approximately half of the global Hg(0) emissions in 2008 followed by
      combustion (29%), cement production (12%) and other metal industry (10%). Given
      the local-scale impacts of mercury, special attention was given to the spatial
      distribution showing the emission hot-spots on gridded 0.1 degrees *0.1 degrees 
      resolution maps using detailed proxy data. The comprehensive ex-post analysis of
      the mitigation of mercury emissions by end-of-pipe abatement measures in the
      power generation sector and technology changes in the chlor-alkali industry over
      four decades indicates reductions of 46% and 93%, respectively. Combined, the
      improved technologies and mitigation measures in these sectors accounted for
      401.7 tonnes of avoided mercury emissions in 2008. A comparison shows that
      EDGARv4 anthropogenic emissions are nearly equivalent to the lower estimates of
      the United Nations Environment Programme (UNEP)'s mercury emissions inventory for
      2005 for most sectors. An evaluation of the EDGARv4 global mercury emission
      inventory, including mercury speciation, was performed using the GEOS-Chem global
      3-D mercury model. The model can generally reproduce both spatial variations and
      long-term trends in total gaseous mercury concentrations and wet deposition
      fluxes.

PMID- 25068707
TI  - Nanogel formation from dilute solutions of clickable elastin-like recombinamers
      and its dependence on temperature: two fractal gelation modes.
AB  - Diluted, complementary, click-reactive elastin-like recombinamer (ELR) solutions
      have been prepared and mixed at two different temperatures, one below and one
      above the characteristic transition temperature (Tt) of these chemically modified
      ELRs. FTIR measurements, size, aspect ratio, zeta potential, and microrheological
      measurements have been carried out on the nanostructures formed under these
      dilute conditions as a way to better understand the relationship between the
      final macroscopic properties of ELR-based hydrogels and the molecular conditions
      governing the initial stages of the chemical cross-linking process that occurs,
      especially its dependence on the preparation temperature relative to Tt. As a
      result, two different fractal modes of gel formation have been found at the two
      temperatures studied (above and below Tt). Thus, when the reaction mixture is
      prepared below Tt, essentially one-dimensional linear nanogels with a high aspect
      ratio are obtained. In contrast, 3D nanogels are formed above Tt, with spherical
      shapes predominating. These different structures seem to reflect the two
      molecular organizations of the single components of the mixture under these
      conditions, namely extended chains below Tt and a spherical arrangement above Tt.
      In addition to the interest in these nanogels as models for understanding the
      formation of microscopic structures and differential macroscopic properties under
      more conventional hydrogel-formation conditions, these nanogels are of interest
      because of their thermoresponsiveness and biocompatibility, which provide them
      with potential uses for drug delivery and other biomedical applications in living
      systems. 

PMID- 25068700
TI  - Receptor for advanced glycation end products (RAGE) and its ligands: focus on
      spinal cord injury.
AB  - Spinal cord injury (SCI) results in neuronal and glial death and the loss of
      axons at the injury site. Inflammation after SCI leads to the inhibition of
      tissue regeneration and reduced neuronal survival. In addition, the loss of axons
      after SCI results in functional loss below the site of injury accompanied by
      neuronal cell body's damage. Consequently, reducing inflammation and promoting
      axonal regeneration after SCI is a worthy therapeutic goal. The receptor for
      advanced glycation end products (RAGE) is a transmembrane protein and receptor of
      the immunoglobulin superfamily. RAGE is implicated in inflammation and
      neurodegeneration. Several recent studies demonstrated an association between
      RAGE and central nervous system disorders through various mechanisms. However,
      the relationship between RAGE and SCI has not been shown. It is imperative to
      elucidate the association between RAGE and SCI, considering that RAGE relates to
      inflammation and axonal degeneration following SCI. Hence, the present review
      highlights recent research regarding RAGE as a compelling target for the
      treatment of SCI. 

PMID- 25068708
TI  - Ligand-induced conformational change of Plasmodium falciparum AMA1 detected using
      19F NMR.
AB  - We established an efficient means of probing ligand-induced conformational change
      in the malaria drug target AMA1 using 19F NMR. AMA1 was labeled with 5
      fluorotryptophan (5F-Trp), and the resulting 5F-Trp resonances were assigned by
      mutagenesis of the native Trp residues. By introducing additional Trp residues at
      strategic sites within a ligand-responsive loop, we detected distinct
      conformational consequences when various peptide and small-molecule ligands bound
      AMA1. Our results demonstrate an increase in flexibility in this loop caused by
      the native ligand, as inferred from, but not directly observed in, crystal
      structures. In addition, we found evidence for long-range allosteric changes in
      AMA1 that are not observed crystallographically. This method will be valuable in
      ongoing efforts to identify and characterize therapeutically relevant inhibitors
      of protein-protein interactions involving AMA1 and is generalizable to the study
      of ligand-induced conformational change in a wide range of other drug targets.

PMID- 25068709
TI  - Turning point revisited: launching the next generation of performance management
      in public health.
AB  - A decade ago, the Turning Point Performance Management Excellence Collaborative
      (Turning Point) developed the first public health-specific performance management
      (PM) system, with accompanying resource materials, assisted by the Public Health
      Foundation. Since then, dramatic advancements in PM and quality improvement
      activities have occurred in public health. Public Health Foundation gathered data
      that revealed Turning Point was still relevant but difficult to implement within
      public health. To reflect recent advances and current challenges, Public Health
      Foundation refreshed the Turning Point model and related guidance tools and
      developed new resources to facilitate PM implementation. In addition, a new fifth
      component, "Visible Leadership," was added to the 4-quadrant model and the Self
      Assessment Tool. In the future, public health organizations should take an active
      leadership role in innovating and sustaining PM systems, ensuring they become
      accountable for producing outcomes, leveraging technology advances, and
      incorporating best practices from all stakeholders. 

PMID- 25068710
TI  - Ferrocene-based supramolecular structures and their applications in
      electrochemical responsive systems.
AB  - Electrochemical stimuli have attracted much attention in recent years as they are
      simple, clean and can be widely applied in biological systems and material
      science. As one type of common guest molecules, ferrocene and its derivatives
      have been well studied with different host molecules, mainly including
      cyclodextrins, cucurbiturils, pillararenes and calixarenes. This article
      generally summarizes the recent work on the host-guest interactions between
      ferrocene derivatives and their host molecules, as well as various supramolecular
      systems based on these interactions. In addition, the development and outlook of
      electrochemical responsive systems are also discussed. 

PMID- 25068712
TI  - A tail of two peptide amphiphiles: effect of conjugation with hydrophobic polymer
      on folding of peptide sequences.
AB  - Peptide amphiphiles (PA) offer the potential of incorporating biological function
      into synthetic materials for tissue engineering in regenerative medicine. These
      hybrid conjugates are known to undergo self-assembly starting from single
      molecules to nanofibers before turning into hydrogel scaffolds-such a process
      involves conformational changes in secondary structures of peptides. Therefore,
      insights on the ability of peptide amphiphiles to form secondary structure as
      single molecules are useful for understanding self-assembly behavior. We report
      here a molecular simulation study of peptide folding by two PA sequences, each
      contains an alkyl tail and short peptide segment. The alkyl tail is observed to
      play two opposing roles in modulating sequence-dependent folding kinetics and
      thermodynamics. On one hand, it restricts conformational freedom reducing the
      entropic cost of folding, which is thus promoted. On the other hand, it acts as
      an interaction site with nonpolar peptide residues, blocking the peptide from
      helix nucleation, which reduces folding. 

PMID- 25068713
TI  - Moving beyond the breast cancer screening debate.

PMID- 25068715
TI  - Early markers of occult megaloblastosis for low-cost detection of
      hyperhomocysteinemia in patients with ischaemic stroke: preventive approach for
      primary health care.
AB  - Recent studies have focussed on the association between elevated homocysteine
      levels with megaloblastic changes and thromboembolic events, but the relationship
      between occult megaloblastosis (with normal haemoglobin levels) and ischaemic
      stroke has not been widely explored. The objective of this study is to establish
      a simple and economical marker for the detection of occult megaloblastosis at the
      community health care level in developing countries. A hundred patients who met
      the inclusion criteria were studied. At the 5% level of significance, the levels
      of cobalamin and folate were significantly lower, while the number of
      hypersegmented neutrophils on the peripheral smear was higher in patients from
      Group A (70 patients with high homocysteine) compared with the patients in Group
      B (30 patients with normal homocysteine). Forty-five (64.2%) of the 70 patients
      in Group A showed hypersegmentation of neutrophils in the peripheral smear. The
      high cost and difficulty in performing the vitamin assays limit their use as
      early markers of megaloblastosis. Hence, we conclude that in developing
      countries, the detection of hypersegmented neutrophils can be used at the primary
      healthcare level for early diagnosis of occult megaloblastosis, so that early
      therapeutic interventions with vitamins can prevent attacks of
      hyperhomocysteinemia-induced ischaemic stroke. 

PMID- 25068718
TI  - Abstracts from the Academy of Managed Care Pharmacy 26th Annual Meeting and Expo,
      April 1-4, 2014, Tampa, Florida.

PMID- 25068717
TI  - Analytical comparison of natural and pharmaceutical ventricular myosin
      activators.
AB  - Ventricular myosin (betaMys) is the motor protein in cardiac muscle generating
      force using ATP hydrolysis free energy to translate actin. In the cardiac muscle
      sarcomere, myosin and actin filaments interact cyclically and undergo rapid
      relative translation facilitated by the low duty cycle motor. It contrasts with
      high duty cycle processive myosins for which persistent actin association is the
      priority. The only pharmaceutical betaMys activator, omecamtive mecarbil (OM),
      upregulates cardiac contractility in vivo and is undergoing testing for heart
      failure therapy. In vitro betaMys step-size, motility velocity, and actin
      activated myosin ATPase were measured to determine duty cycle in the absence and
      presence of OM. A new parameter, the relative step-frequency, was introduced and
      measured to characterize betaMys motility due to the involvement of its three
      unitary step-sizes. Step-size and relative step-frequency were measured using the
      Qdot assay. OM decreases motility velocity 10-fold without affecting step-size,
      indicating a large increase in duty cycle converting betaMys to a near processive
      myosin. The OM conversion dramatically increases force and modestly increases
      power over the native betaMys. Contrasting motility modification due to OM with
      that from the natural myosin activator, specific betaMys phosphorylation,
      provides insight into their respective activation mechanisms and indicates the
      boilerplate screening characteristics desired for pharmaceutical betaMys
      activators. New analytics introduced here for the fast and efficient Qdot
      motility assay create a promising method for high-throughput screening of motor
      proteins and their modulators. 

PMID- 25068716
TI  - Striatal dopamine homeostasis is altered in mice following Roux-en-Y gastric
      bypass surgery.
AB  - Roux-en-Y gastric bypass (RYGB) is an effective treatment for obesity.
      Importantly, weight loss following RYGB is thought to result in part from changes
      in brain-mediated regulation of appetite and food intake. Dopamine (DA) within
      the dorsal striatum plays an important role in feeding behavior; we therefore
      hypothesized that RYGB alters DA homeostasis in this subcortical region. In the
      current study, obese RYGB-operated mice consumed significantly less of a high-fat
      diet, weighed less by the end of the study, and exhibited lower adiposity than
      obese sham-operated mice. Interestingly, both RYGB and caloric restriction (pair
      feeding) resulted in elevated DA and reduced norepinephrine (NE) tissue levels
      compared with ad libitum fed sham animals. Consequently, the ratio of NE to DA, a
      measure of DA turnover, was significantly reduced in both of these groups. The
      RYGB mice additionally exhibited a significant increase in phosphorylation of
      tyrosine hydroxylase at position Ser31, a key regulatory site of DA synthesis.
      This increase was associated with augmented expression of extracellular-signal
      regulated kinases ERK1/2, the kinase targeting Ser31. Additionally, RYGB has been
      shown in animal models and humans to improve insulin sensitivity and glycemic
      control. Curiously, we noted a significant increase in the expression of insulin
      receptor-beta in RYGB animals in striatum (a glucosensing brain region) compared
      to sham ad libitum fed mice. These data demonstrate that RYGB surgery is
      associated with altered monoamine homeostasis at the level of the dorsal
      striatum, thus providing a critical foundation for future studies exploring
      central mechanisms of weight loss in RYGB.

PMID- 25068719
TI  - High-performance liquid chromatography-based method to evaluate kinetics of
      glucosinolate hydrolysis by Sinapis alba myrosinase.
AB  - Isothiocyanates (ITCs) are one of several hydrolysis products of glucosinolates,
      plant secondary metabolites that are substrates for the thioglucohydrolase
      myrosinase. Recent pursuits toward the development of synthetic non-natural ITCs
      have consequently led to an exploration of generating these compounds from non
      natural glucosinolate precursors. Evaluation of the myrosinase-dependent
      conversion of select non-natural glucosinolates to non-natural ITCs cannot be
      accomplished using established ultraviolet-visible (UV-Vis) spectroscopic
      methods. To overcome this limitation, an alternative high-performance liquid
      chromatography (HPLC)-based analytical approach was developed where initial
      reaction velocities were generated from nonlinear reaction progress curves.
      Validation of this HPLC method was accomplished through parallel evaluation of
      three glucosinolates with UV-Vis methodology. The results of this study
      demonstrate that kinetic data are consistent between both analytical methods and
      that the tested glucosinolates respond similarly to both Michaelis-Menten and
      specific activity analyses. Consequently, this work resulted in the complete
      kinetic characterization of three glucosinolates with Sinapis alba myrosinase,
      with results that were consistent with previous reports. 

PMID- 25068721
TI  - Formulation optimization and in vivo proof-of-concept study of thermosensitive
      liposomes balanced by phospholipid, elastin-like polypeptide, and cholesterol.
AB  - One application of nanotechnology in medicine that is presently being developed
      involves a drug delivery system (DDS) employing nanoparticles to deliver drugs to
      diseased sites in the body avoiding damage of healthy tissue. Recently, the mild
      hyperthermia-triggered drug delivery combined with anticancer agent-loaded
      thermosensitive liposomes was widely investigated. In this study, thermosensitive
      liposomes (TSLs), composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC),
      1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)
      2000] (DSPE-PEG), cholesterol, and a fatty acid conjugated elastin-like
      polypeptide (ELP), were developed and optimized for triggered drug release,
      controlled by external heat stimuli. We introduced modified ELP, tunable for
      various biomedical purposes, to our thermosensitive liposome (e-TSL) to convey a
      high thermoresponsive property. We modulated thermosensitivity and stability by
      varying the ratios of e-TSL components, such as phospholipid, ELP, and
      cholesterol. Experimental data obtained in this study corresponded to results
      from a simulation study that demonstrated, through the calculation of the lateral
      diffusion coefficient, increased permeation of the lipid bilayer with higher ELP
      concentrations, and decreased permeation in the presence of cholesterol. Finally,
      we identified effective drug accumulation in tumor tissues and antitumor efficacy
      with our optimized e-TSL, while adjusting lag-times for systemic accumulation. 

PMID- 25068722
TI  - Determination of strain-rate-dependent mechanical behavior of living and fixed
      osteocytes and chondrocytes using atomic force microscopy and inverse finite
      element analysis.
AB  - The aim of this paper is to determine the strain-rate-dependent mechanical
      behavior of living and fixed osteocytes and chondrocytes, in vitro. First, atomic
      force microscopy (AFM) was used to obtain the force-indentation curves of these
      single cells at four different strain-rates. These results were then employed in
      inverse finite element analysis (FEA) using modified standard neo-Hookean solid
      (MSnHS) idealization of these cells to determine their mechanical properties. In
      addition, a FEA model with a newly developed spring element was employed to
      accurately simulate AFM evaluation in this study. We report that both
      cytoskeleton (CSK) and intracellular fluid govern the strain-rate-dependent
      mechanical property of living cells whereas intracellular fluid plays a
      predominant role on fixed cells' behavior. In addition, through the comparisons,
      it can be concluded that osteocytes are stiffer than chondrocytes at all strain
      rates tested indicating that the cells could be the biomarker of their tissue
      origin. Finally, we report that MSnHS is able to capture the strain-rate
      dependent mechanical behavior of osteocyte and chondrocyte for both living and
      fixed cells. Therefore, we concluded that the MSnHS is a good model for
      exploration of mechanical deformation responses of single osteocytes and
      chondrocytes. This study could open a new avenue for analysis of mechanical
      behavior of osteocytes and chondrocytes as well as other similar types of cells. 

PMID- 25068720
TI  - Global burden of HIV among men who engage in transactional sex: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Men who engage in transactional sex, the exchange of sex for money,
      goods, or other items of value, are thought to be at increased risk of HIV, but
      there have been no systematic attempts to characterize HIV burden in this
      population. We undertook a systematic review and meta-analysis to quantify the
      burden in this population compared with that of men in the general population to
      better inform future HIV prevention efforts. METHODS: We searched seven
      electronic databases, national surveillance reports, and conference abstracts for
      studies of men who engage in transactional sex published between 2004-2013.
      Random effects meta-analysis was used to determine pooled HIV prevalence and
      prevalence ratios (PR) for the difference in HIV prevalence among men who engage
      in transactional sex as compared to general population men. FINDINGS: Of 66
      studies included representing 31,924 men who had engaged in transactional sex in
      28 countries, pooled biological assay-confirmed HIV prevalence was 10.5% (95% CI
      = 9.4 to 11.5%). The highest pooled HIV prevalence was in Sub-Saharan Africa
      (31.5%, 95% CI = 21.6 to 41.5%), followed by Latin America (19.3%, 95% CI = 15.5
      to 23.1%), North America (16.6%, 95% CI = 3.7 to 29.5%), and Europe (12.2%, 95%
      CI = 6.0 to 17.2%). Men who engaged in transactional sex had an elevated burden
      of HIV compared to the general male population (PR = 20.7, 95% CI = 16.8 to
      25.5). CONCLUSIONS: The global burden of HIV is disproportionately high among men
      who engage in transactional sex compared with the general male population. There
      is an urgent need to include this population in systematic surveillance as well
      as to scale-up access to quality HIV prevention programs.

PMID- 25068724
TI  - An insight into the exploration of druggable genome of Streptococcus gordonii for
      the identification of novel therapeutic candidates.
AB  - The discovery of novel drug targets of a genome that can bind with high affinity
      to drug-like compounds is a significant challenge in drug development.
      Streptococcus gordonii initiates dental plaque formation and endocarditis by
      entering into the blood stream, usually after oral trauma. The prolonged use of
      antibiotics is raising a problem of multi-drug resistance and lack of an optimal
      therapeutic regime that necessitates the drug discovery of vital importance in
      curing various infections. To overcome this dilemma, the in silico approach paves
      the way for identification and qualitative characterization of promising drug
      targets for S. gordonii that encompass three phases of analyses. The present
      study deciphers drug target genomes of S. gordonii in which 93 proteins were
      identified as potential drug targets and 16 proteins were found to be involved in
      unique metabolic pathways. Highlighted information will convincingly render to
      facilitate selection of S. gordonii proteins for successful entry into drug
      design pipelines. 

PMID- 25068723
TI  - Electrophysiological explorations of the bilingual advantage: evidence from a
      Stroop task.
AB  - Bilinguals have been shown to exhibit a performance advantage on executive
      control tasks, outperforming their monolingual counterparts. Although a wealth of
      research has investigated this 'bilingual advantage' behaviourally,
      electrophysiological correlates are lacking. Using EEG with a Stroop task that
      manipulated the stimulus onset asynchrony (SOA) of word and colour presentation,
      the current study addressed two facets of the bilingual advantage. The
      possibility that bilinguals experience superior conflict processing relative to
      monolinguals (a 'conflict-specific advantage') was investigated by comparing
      behavioural interference effects as well as the amplitude of the Ninc, a conflict
      related ERP component occurring from approximately 300-500 ms after the onset of
      conflict. In contrast, the hypothesis that bilinguals experience domain-general,
      conflict-independent enhancements in executive processing (a 'non-conflict
      specific advantage') was evaluated by comparing the control condition (symbol
      strings) between groups. There was some significant, but inconsistent, evidence
      for a conflict-specific bilingual advantage. In contrast, strong evidence emerged
      for a non-conflict-specific advantage, with bilinguals demonstrating faster RTs
      and reduced ERP amplitudes on control trials compared to monolinguals.
      Importantly, when the control stimulus was presented before the colour, ERPs to
      control trials revealed group differences before the onset of conflict,
      suggesting differences in the ability to ignore or suppress distracting
      irrelevant information. This indicates that bilinguals experience superior
      executive processing even in the absence of conflict and semantic salience, and
      suggests that the advantage extends to more efficient proactive management of the
      environment. 

PMID- 25068725
TI  - Rotation motion of designed nano-turbine.
AB  - Construction of nano-devices that can generate controllable unidirectional
      rotation is an important part of nanotechnology. Here, we design a nano-turbine
      composed of carbon nanotube and graphene nanoblades, which can be driven by fluid
      flow. Rotation motion of nano-turbine is quantitatively studied by molecular
      dynamics simulations on this model system. A robust linear relationship is
      achieved with this nano-turbine between its rotation rate and the fluid flow
      velocity spanning two orders of magnitude, and this linear relationship remains
      intact at various temperatures. More interestingly, a striking difference from
      its macroscopic counterpart is identified: the rotation rate is much smaller (by
      a factor of ~15) than that of the macroscopic turbine with the same driving flow.
      This discrepancy is shown to be related to the disruption of water flow at
      nanoscale, together with the water slippage at graphene surface and the so-called
      "dragging effect". Moreover, counterintuitively, the ratio of "effective" driving
      flow velocity increases as the flow velocity increases, suggesting that the
      linear dependence on the flow velocity can be more complicated in nature. These
      findings may serve as a foundation for the further development of rotary nano
      devices and should also be helpful for a better understanding of the biological
      molecular motors. 

PMID- 25068727
TI  - Chromatographic evaluation and QSAR optimization for benzoic acid analogues
      against carbonic anhydrase III.
AB  - An HPLC-size exclusion method was developed as an assay method to evaluate the
      binding of tested compounds with carbonic anhydrase III (CAIII) enzyme.
      Inhibition of CAIII by a group of benzoic acid analogues was characterized by
      vacancy (negative) peak intensity representing the fraction of the compounds
      bound with CAIII enzyme. Interestingly, p-hydroxyl benzoic acid and aspirin were
      found potent inhibitors against CAIII with affinity constants of 9954 and 9013 M(
      1) respectively. Affinity values of twenty training compounds were modeled
      against thirty-five descriptors derived from their structures. Strong correlation
      was obtained between the affinity values and the formal charge of the molecules.
      Docking studies on training set compounds generated consensus scores having a
      strong agreement with affinity factors obtained from the chromatographic
      analysis. 

PMID- 25068728
TI  - A convenient synthesis and molecular modeling study of novel pyrazolo[3,4
      d]pyrimidine and pyrazole derivatives as anti-tumor agents.
AB  - An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3)
      was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide
      with (E)-ethyl 2-cyano-3-ethoxyacrylate. The cyclocondensation reaction of this
      substrate and its hydrazide derivative with urea, thiourea, formamide, formic
      acid, d-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9
      carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate
      analogues furnished a series of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-d]oxazin
      4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4
      oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively.
      The structure of the compound 3 was supported by X-Ray crystallographic data.
      Orally administrated, one of each of the series of pyrazoles showed significant
      effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell
      lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies. 

PMID- 25068729
TI  - Synthesis and biological evaluation of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta
      1,4-dien-3-one and its aminomethyl derivatives.
AB  - Aminomethyl derivatives of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3
      one, designed as new cytotoxins, were synthesized and evaluated in terms of their
      cytotoxic activities. The compounds have low CC50 values in the low micromolar
      range against HL-60 neoplasms and HSC-2, HSC-3 and HSC-4 carcinoma cells. In
      general, the average CC50 values of these compounds were higher towards HGF, HPC
      and HPLF non-malignant cells, which reveals the tumour-selectivity of these
      aminomethyl derivatives, Mannich bases. Using specific concentrations of
      compounds 4 and 6 caused cleavage of PARP1 in HSC-2 cells but not HGF cells,
      which may be a contributing factor to cytotoxicities and the tumour
      selectivities. 

PMID- 25068730
TI  - Synthesis and evaluation of N-heteroarylsubstituted triazolosulfonamides as
      carbonic anhydrase inhibitors.
AB  - A new series of N-heteroarylsubstituted triazolosulfonamide compounds were
      synthesized and their inhibitory effects on the activity of purified human
      carbonic anhydrase (hCA) I and II were evaluated. Compounds (3 a-k) were prepared
      by propargylation of N-heteroaryl compounds. Compound 5 was obtained from
      sulfanilamide and sodium nitrite followed by addition of sodium azide. The
      products (6 a-k) were synthesized from compounds 3 and 5. The results showed that
      all the synthesized compounds were inhibited the CA isoenzymes activity. Figure
      6a (IC50 = 0.52 uM for hCA I and 0.34 uM for hCA II) has the most inhibitory
      effect among the synthesized compounds. 

PMID- 25068731
TI  - Synthesis of new isoxazoline derivatives from harmine and evaluation of their
      anti-Alzheimer, anti-cancer and anti-inflammatory activities.
AB  - In our study, a series of new harmine derivatives has been prepared by
      cycloaddition reaction using various arylnitrile oxides and evaluated in vitro
      against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer
      cell lines. Some of these molecules have been shown to be potent inhibitors of
      acetylcholinesterase and MCF7 cell line. The greatest activity against
      acetylcholinesterase (IC50 = 10.4 uM) was obtained for harmine 1 and cytotoxic
      activities (IC50 = 0.2 uM) for compound 3a. Two derivatives 3e and 3f with the
      thiophene and furan systems, respectively, showed good activity against 5-
      lipoxygenase enzyme (IC50 = 29.2 and 55.5 uM, respectively). 

PMID- 25068732
TI  - Simultaneous interfacial rheology and microstructure measurement of densely
      aggregated particle laden interfaces using a modified double wall ring
      interfacial rheometer.
AB  - The study of particle laden interfaces has increased significantly due to the
      increasing industrial use of particle stabilized foams and Pickering emulsions,
      whose bulk rheology and stability are highly dependent on particle laden
      interface's interfacial rheology, which is a function of interfacial
      microstructure. To understand the physical mechanisms that dictate interfacial
      rheology of particle laden interfaces requires correlating rheology to
      microstructure. To achieve this goal, a double wall ring interfacial rheometer
      has been modified to allow real time, simultaneous interfacial visualization and
      shear rheology measurements. The development of this tool is outlined, and its
      ability to provide novel and unique measurements is demonstrated on a sample
      system. This tool has been used to examine the role of microstructure on the
      steady shear rheology of densely packed, aggregated particle laden interfaces at
      three surface concentrations. Through examination of the rheology and analysis of
      interfacial microstructure response to shear, a transition from shear thinning
      due to aggregated cluster breakup to yielding at a slip plane within the
      interface has been identified. Interestingly, it is found that aggregated
      interfaces transition to yielding well before they reached a jammed state.
      Furthermore, these systems undergo significant shear induced order when densely
      packed. These results indicate that the mechanics of these interfaces are not
      simply jammed or unjammed and that the interfacial rheology relationship with
      microstructure can give us significant insight into understanding how to engineer
      particle laden interfaces in the future. By examining both rheology and
      microstructure, the mechanisms that dictate observed rheology are now understood
      and can be used to predict and control the rheology of the interface. 

PMID- 25068733
TI  - In vitro and in vivo induction of cytochrome P450 by coplanar
      polychlorinated/brominated biphenyls (Co-PXBs) providing high TEQ in mother's
      milk in Japan.
AB  - Coplanar polychlorinated/brominated biphenyls (Co-PXBs) are environmental
      pollutants previously identified in market fish samples. In this study, we
      observed that mother's milk in Japan is contaminated with Co-PXBs. Based on
      assumption that the toxicity of the same congener of PXDDs/DFs and Co-PXBs is
      nearly equal to that of the corresponding PCDDs/DFs and Co-PCBs, respectively,
      the toxic equivalent (TEQ) concentration was 10% of the total TEQ concentration
      (?PCDDs/DFs, ?PXDDs/DFs, ?Co-PCBs and ?Co-PXBs) in the milk. This observation
      suggested that humans, and especially infants, are exposed to high levels of Co
      PXBs, which might cause adverse effects. However, the toxicity of Co-PXBs has to
      date not been reported. We assessed the toxic potency of Co-PXBs by studying
      their effect on the activity of cytochrome P450. Only the mRNA level and activity
      of CYP1A increased in a dose-dependent manner upon exposure to Co-PXBs.
      Substitution of bromine for chlorine into Co-PCBs provided higher CYP1A activity
      in in vitro and in vivo experiments. The expression level of aryl hydrocarbon
      receptor (AhR) mRNA was not altered, but luciferase activity, an indicator of AhR
      transcriptional activity, increased following treatment with Co-PXBs. The results
      suggest that CYP1A induction by Co-PXBs depended on AhR transcriptional activity
      and not on AhR expression. Although the TEFs of Co-PXBs are not set, if Co-PXBs
      are included in these calculations because of their higher toxicity compared to
      Co-PCBs, exposure to Co-PXBs cannot be neglected when assessing human health
      risks. 

PMID- 25068734
TI  - Direct detection of the gel-fluid phase transition of a single supported
      phospholipid bilayer using quartz crystal microbalance with dissipation
      monitoring.
AB  - Supported phospholipid bilayers (SPBs) are valuable models for fundamental
      studies of biological membranes and their interaction with biologically relevant
      solutes or particles. Herein, we demonstrate the capability of the quartz crystal
      microbalance with dissipation monitoring (QCM-D) to directly detect the gel-fluid
      phase transition of a SPB. The approach involves comparison of the frequency
      response of a bare and a bilayer-coated QCM-D crystal during linear temperature
      variation. Phase transition results in a change of the resonance frequency that
      coincides directly with the accompanied change in bilayer thickness detected by
      ellipsometry. Experiments performed at different heating rates further
      demonstrate the use of dissipation monitoring to determine the phase transition
      temperature based on the temperature-induced viscosity changes of the ambient
      medium in the immediate environment of the bilayer. Unlike other methods, the
      proposed approach enables precise determination of the phase transition of a SPB
      without the need for thermal equilibration of the measurement chamber and, thus,
      has great potential for sensitive detection of structural and/or compositional
      changes of the bilayer. 

PMID- 25068735
TI  - Light-sheet functional imaging in fictively behaving zebrafish.

PMID- 25068737
TI  - Throwing speed and accuracy in baseball and cricket players.
AB  - Throwing speed and accuracy are both critical to sports performance but cannot be
      optimized simultaneously. This speed-accuracy trade-off (SATO) is evident across
      a number of throwing groups but remains poorly understood. The goal was to
      describe the SATO in baseball and cricket players and determine the speed that
      optimizes accuracy. 20 grade-level baseball and cricket players performed 10
      throws at 80% and 100% of maximal throwing speed (MTS) toward a cricket stump.
      Baseball players then performed a further 10 throws at 70%, 80%, 90%, and 100% of
      MTS toward a circular target. Baseball players threw faster with greater accuracy
      than cricket players at both speeds. Both groups demonstrated a significant SATO
      as vertical error increased with increases in speed; the trade-off was worse for
      cricketers than baseball players. Accuracy was optimized at 70% of MTS for
      baseballers. Throwing athletes should decrease speed when accuracy is critical.
      Cricket players could adopt baseball-training practices to improve throwing
      performance.

PMID- 25068736
TI  - Mapping brain activity at scale with cluster computing.
AB  - Understanding brain function requires monitoring and interpreting the activity of
      large networks of neurons during behavior. Advances in recording technology are
      greatly increasing the size and complexity of neural data. Analyzing such data
      will pose a fundamental bottleneck for neuroscience. We present a library of
      analytical tools called Thunder built on the open-source Apache Spark platform
      for large-scale distributed computing. The library implements a variety of
      univariate and multivariate analyses with a modular, extendable structure well
      suited to interactive exploration and analysis development. We demonstrate how
      these analyses find structure in large-scale neural data, including whole-brain
      light-sheet imaging data from fictively behaving larval zebrafish, and two-photon
      imaging data from behaving mouse. The analyses relate neuronal responses to
      sensory input and behavior, run in minutes or less and can be used on a private
      cluster or in the cloud. Our open-source framework thus holds promise for turning
      brain activity mapping efforts into biological insights. 

PMID- 25068738
TI  - The need to consider relative age effects in women's talent development process.
AB  - Relative age effects (RAEs) refer to age differences among athletes in the same
      selection year. This study analyzed birth date distributions of 301,428 female
      athletes (aged 10-20 yr.) in Swiss Youth sports and the subgroup (n = 1,177) of
      the National Talent Development Program (TDP) in individual sports. Comparisons
      showed significant RAEs in the distribution of athletes' birth dates in alpine
      skiing, tennis, athletics, fencing, and snowboarding. Significant "reverse" RAEs
      with an overrepresentation of athletes at the end of the year were found in table
      tennis. In the TDP, significant RAEs were found in alpine skiing and tennis. No
      RAEs were detected in athletics. In table tennis, fencing, and snowboarding,
      "reverse" RAEs were found. Clearly, RAEs are complex and vary across individual
      sports for females.

PMID- 25068739
TI  - Adolescents' physical activity in physical education, school recess, and extra
      curricular sport by motivational profiles.
AB  - The main purpose of this study was to evaluate the differences in adolescents'
      objective physical activity levels and perceived effort in physical education,
      school recess, and extra-curricular organized sport by motivational profiles in
      physical education. A sample of 102 students 11-16 yr. old completed a self
      report questionnaire assessing self-determined motivation toward physical
      education. Subsequently, students' objective physical activity levels
      (steps/min., METs, and moderate-to-vigorous physical activity) and perceived
      effort were evaluated for each situation. Cluster analysis identified a two
      cluster structure: "Moderate motivation toward physical education profile" and
      "High motivation toward physical education profile." Adolescents in the second
      cluster had higher physical activity and perceived effort values than adolescents
      in the first cluster, except for METs and moderate-to-vigorous physical activity
      in extra-curricular sport. These results support the importance of physical
      education teachers who should promote self-determined motivation toward physical
      education so that students can reach the recommended physical activity levels.

PMID- 25068740
TI  - Recording frequency-following responses to voice pitch in guinea pigs:
      preliminary results.
AB  - Although scalp-recorded frequency-following response (FFR) to voice pitch has
      shown great potential to examine pitch processing mechanisms in human
      participants and animals, few reports have addressed the test-retest reliability
      of such a response in an animal model. The purpose of this study was to
      investigate the feasibility and reliability of recording such a response in an
      animal model and to evaluate the extent to which the response could be separated
      from background noise. A Chinese monosyllable with a rising pitch was used to
      elicit the FFR to voice pitch in four guinea pigs. Four objective measures (Root
      Mean-Square, Amplitude, Tracking Accuracy, Frequency Error, and Slope Error) were
      computed from recorded brain waves and were used to examine the phase-locking
      magnitude and test-retest reliability of the response. Results demonstrated that
      the animal model produced FFR trends that were repeatable, reliable, and
      significantly different from responses to the background noise.

PMID- 25068741
TI  - Promoting English oral communication and higher-order thinking in Taiwanese ESL
      students through the use of knowledge visualization techniques.
AB  - The study examined whether the students using concept mapping in a Freshman
      English course would improve English oral communication proficiency, higher-order
      thinking, and perception of abilities. A quasi-experimental design, lasting for
      12 weeks, was administered to an experimental group (21 students) and a control
      group (20 students). The experimental group had significantly better performance
      on all measures. Concept mapping was effective in improving college students'
      English oral communication, higher-order thinking, and perception of abilities
      development.

PMID- 25068743
TI  - Attention and blood lactate levels in equestrians performing show jumping.
AB  - In equestrian show jumping, attention is particularly important to ensure maximum
      accuracy. Due to the anaerobic nature of the jumping and its requirement for
      precision coordination between human and horse, there may be a relation between
      the onset of lactic threshold and decrease in attention. In 12 healthy and injury
      free equestrians (6 men, 6 women), the effects (blood lactate and glucose) of a
      show jumping course (250 m long with eight vertical obstacles with a height of
      1.15 m height) on capacity and selectivity of attention was assessed. A typical
      reaction time paradigm and test of divided attention were administered. At the
      end of the course a significant increase of blood lactate was observed, whereas
      blood glucose did not significantly change. A deterioration of attention
      (intensity and selectivity) and a worsening of performance with increasing of
      blood lactate were observed. The present results led to the conclusion that the
      increase in blood lactate that occurs in riders executing a show jumping course
      is associated with worsening of both attentive capabilities and performance.

PMID- 25068742
TI  - An assessment of the effects of navigation maps on drivers' mental workloads.
AB  - This study compares the mental workloads and subjective feelings of drivers
      navigating different road patterns using different formats of electronic and
      paper maps. The results show drivers experience lower mental workloads when using
      2D electronic maps compared to 3D electronic maps. Significant differences in
      galvanic skin responses were observed for navigation map formats with different
      road intersection patterns. The low- and high-frequency components of heart rate
      variability showed significant differences between map formats for regular road
      intersections, but no significant differences between map formats for irregular
      road intersections. Statistically significant effects on subjective feelings were
      found between different map formats and road intersection patterns. The wider
      implications of the study results for the design and use of navigation map
      interfaces are discussed.

PMID- 25068744
TI  - Design and evaluation of a computerized test for hand motor skills.
AB  - The purposes of this study are to design and develop a computerized test to
      measure junior high school students' motor skills, specifically their abilities
      in hand-eye motor coordination and hand motor skills, using the Wii Remote. The
      hand motor skills computerized test, which is based on the operational
      examinations in the General Aptitude Test Battery, examines hand and finger
      dexterity (i.e., motion, rotation, fabrication, and disassembly tests). 55
      students participated in the experiment to assess the reliability and validity of
      the computerized test, which were supported. Information literacy and experience
      in the use of Wii devices did not affect the reliability.

PMID- 25068745
TI  - Use of objective psychomotor tests in health professionals.
AB  - Evaluation of psychomotor skills is undertaken in a number of broad contexts.
      This includes testing of health professional populations as a measure of innate
      ability, to evaluate skill acquisition, or to compare professions. However, the
      use of psychomotor tests is frequently confounded by a lack of understanding of a
      particular tool's psychometric properties, strengths, and weaknesses. To identify
      and appraise the most commonly used tests on health professional populations, 86
      articles were reviewed and the top nine tests identified. Few tests have had
      sufficient validity or reliability testing on health professionals. Based on the
      evidence available, use of the Grooved Pegboard Test, the Purdue Pegboard Test,
      or the Finger Tapping Test is recommended for the evaluation of dexterity in a
      health professional population; however, this choice may be dependent on the
      task(s) to which findings are generalised. More rigorous evaluation of validity
      and other psychometric properties is required.

PMID- 25068746
TI  - Ebbinghaus illusions with disc figures: effects of contextual size, separation,
      and lightness.
AB  - The Ebbinghaus illusion was produced using figures with four small or large
      contextual discs located either near or far from the central disc. For similar
      figures, the discs were either all black or all white; for dissimilar figures,
      black and white contextual and central discs were used in opposition. 48
      observers, in equal numbers, were assigned to one of the four crossings of size
      and separation of the contextual discs and, using the converging method of
      limits, illusion magnitude scores for each Ebbinghaus configuration were
      obtained. The central disc appeared larger when bounded by small contextual discs
      and smaller when the contextual discs were more distant. Contrary to size
      contrast theory, uniformly colored discs did not generate greater illusions;
      instead, white central discs appeared larger than black ones regardless of
      contextual color. Collectively, the results indicated that contour interactions
      play a prominent role in producing the Ebbinghaus illusion.

PMID- 25068747
TI  - Corporal artistic training influences attention: a pilot study.
AB  - This study assessed the effect of the Body Rhythmics (BRIM) on actors'
      attentional processes. BRIM is a combination of exercises using numbers and rules
      that enact musical parameters in the moving body through displacements. Male
      actors (N = 22) participated in the study: 7 in the BRIM (Study) group and 15 in
      the Control group (groups were equivalent on mean Raven's IQ). The Continuous
      Performance Test (CPT-II) was administered before and after an intensive period
      of BRIM training. There was no significant difference on the CPT-II before
      training. Group results for before vs after training showed a significant
      difference for reaction time for the Study group. There was also a trend to
      increased errors of commission in the Study group after BRIM training.

PMID- 25068748
TI  - Interpretation and perception of slow, moderate, and fast swimming paces in
      distance and sprint swimmers.
AB  - This study assessed how accurately professional swimmers can interpret
      instructions to swim "slow," "moderate," and "fast." 8 distance swimmers (6
      males, 2 females; M age = 19 yr., SD = 3) and 8 sprint swimmers (7 males, 1
      female; M age = 18 yr., SD = 1) performed an all-out 50-m crawl stroke and three
      sets of 8 * 50-m crawl stroke trials interpreting the coach's instruction to swim
      at slow, moderate, and fast paces. No differences were detected between groups in
      absolute speed. Nevertheless, distance and sprint swimmers significantly differed
      in speed normalized to their own 50-m all-out speed (effect sizes = 6.72, 6.20,
      1.35 for slow, moderate, and fast, respectively), stroke frequency (effect sizes
      = 0.81, 1.12, 1.54, respectively), and blood lactate concentration (effect sizes
      = 0.99, 2.56, 1.70, respectively).

PMID- 25068749
TI  - Visual attention to reference frames affects perceptions of shape from shading.
AB  - Perception of shape from shading is processed locally in a bottom-up manner, but
      is also influenced by global or contextual factors. This study examined the
      influence of attention to the reference frame on the perception of shape from
      shading. In a visual search task, participants were asked to identify the
      location of a target relative to the reference frame. The results showed that
      shaded targets were more quickly and accurately detected when the shading
      gradient was parallel, rather than orthogonal, to the orientation of the
      environmental reference frame. This was further supported by a second experiment
      with a masking paradigm. Consequently, the perceptual process of shape from
      shading may be a flexible mechanism in which the representation of gradient
      orientation is calibrated by top-down processing in visual attention.

PMID- 25068751
TI  - Two men with advanced amyotrophic lateral sclerosis operate a computer-aided
      television system through mouth or throat microswitches.
AB  - This study assessed a simple technology to enable two men affected by amyotrophic
      lateral sclerosis, in an advanced stage (i.e., with pervasive motor disabilities
      and lack of speech), to operate a computer-aided television system. The
      technology included microswitches, a portable computer, an interface connecting
      the microswitches to the computer, a commercial software package to allow the
      possibility of watching television via computer, and specific software to allow
      microswitch activations to be recorded as forward commands for channel change.
      The participants (a) gained control over the television programs to watch or not
      to watch (i.e., through channel changes) and (b) showed increased attention to
      the programs (i.e., an increase in their watching time). The practical relevance
      of the findings, the integration of the technology used in this study within the
      participants' wider recreation and communication program, and ways of extending
      the research were discussed.

PMID- 25068750
TI  - Prediction of VO2 peak using OMNI Ratings of Perceived Exertion from a submaximal
      cycle exercise test.
AB  - The primary aim of this study was to develop statistical models to predict peak
      oxygen consumption (VO2 peak) using OMNI Ratings of Perceived Exertion measured
      during submaximal cycle ergometry. Male (M = 20.9 yr., SE = 0.4) and female (M =
      21.6 yr., SE = 0.5) participants (N = 81) completed a load-incremented maximal
      cycle ergometer exercise test. Simultaneous multiple linear regression was used
      to develop separate VO2 peak statistical models using submaximal ratings of
      perceived exertion for the overall body, legs, and chest/breathing as predictor
      variables. VO2 peak (L.min(-1)) predicted for men and women from ratings of
      perceived exertion for the overall body (3.02 +/- 0.06; 2.03 +/- 0.04), legs
      (3.02 +/- 0.06; 2.04 +/- 0.04), and chest/breathing (3.02 +/- 0.05; 2.03 +/-
      0.03) were similar to measured VO2 peak (3.02 +/- 0.10; 2.03 +/- 0.06, ps > .05).
      Statistical models based on submaximal OMNI Ratings of Perceived Exertion provide
      an easily administered and accurate method to predict VO2 peak.

PMID- 25068752
TI  - Heart rate variability differs between right- and left-handed individuals.
AB  - Previous studies reported reduced longevity in left-handers with the suggestion
      that it may be associated with different heart diseases. Therefore, differences
      in heart rate variability (HRV), an index of autonomic cardiac activity, were
      examined for right- and left-handed individuals. 120 healthy young university
      students (75 women, 45 men; M age = 20.4 yr., SD = 1.5) volunteered. Handedness
      was assessed with the Edinburgh Handedness Inventory and HRV was measured via
      electrocardiography. The results suggest that the left-handers' HRV was
      significantly different from that of right-handers on several parameters. The
      atypical cerebral organization of left-handers may be related to an imbalanced
      autonomic system that results in higher frequencies of heart irregularities.

PMID- 25068753
TI  - Bender-gradual scoring system: performance of Brazilian and Peruvian children.
AB  - This is a transcultural study of a sample of Peruvian and Brazilian children
      using the Bender-Gradual Scoring System (B-SPG), which considers shape distortion
      as the only aspect to be analyzed, assuming that perceptual-motor maturity is
      independent of cultural context. The study verified that the scoring system has
      psychometric qualities such that it may be applied in another country. The sample
      consisted of 231 children, ages 6 to 10 yr., 108 from different districts of the
      province Lima in Peru, and 123 children from three states in Brazil. During test
      application, the figures were projected to children in groups. Scoring the
      protocols for errors was conducted by psychologists experienced in interpreting
      and correcting the Bender-SPG, who rigorously followed instructions in Portuguese
      and Spanish. The results obtained with Differential Item Functioning (DIF)
      analysis indicated that Figures 1 and 4 presented DIF, one favoring Brazilian
      children and the other Peruvian children. Thus, it was concluded that the overall
      scores did not favor either population and the Bender-SPG could be used to
      evaluate perceptual-motor maturity in both countries.

PMID- 25068754
TI  - An exploratory study on the relationship between parents' passion for
      sport/exercise and children's self- and task-perceptions in sport/exercise.
AB  - This study investigated the relationship between parents' passion for
      sport/exercise and children's self- and task-perceptions in sport and exercise.
      Paired samples of 312 children, 312 fathers, and 312 mothers were collected using
      two-stage sampling; parents were classified based on their passion for sport and
      exercise as high concordance if both parents had a high passion for sport and
      exercise, low concordance if neither parent had a passion for sport and exercise,
      or discordant. Intrinsic interest value, attainment value/importance, extrinsic
      utility value, ability/expectancy, task difficulty, and required effort were
      measured, as well as harmonious and obsessive passion. Children's self- and task
      perceptions in sport and exercise were examined with respect to parents' passion
      for sport and exercise. The results of the study indicated that children of
      parents with high concordance in harmonious passion for sport and exercise scored
      higher on intrinsic interest value, attainment value/importance, extrinsic
      utility value, ability/expectancy, task difficulty, and required effort in sport
      and exercise than counterparts with discordant and low concordance parents.
      Similar patterns were found for obsessive passion in parents.

PMID- 25068755
TI  - Rating of perceived exertion and affective responses during Tai Chi Chuan.
AB  - Ratings of perceived exertion (RPE) and affective responses were assessed during
      Tai Chi Chuan. A total of 16 women (M age = 61.2 yr., SD = 8.8) participated in
      this study. Individuals practiced Tai Chi Chuan three times/week during seven
      weeks, and were assessed session-by-session (21 Wu Tai Chi Chuan sessions) in
      three moments (15, 30, and 45 min.) using Borg's scale (CR 0-10) and the Feeling
      Scale (+5/-5). With regard to RPE, there was a difference between 15 and 30 min.
      and between 15 and 45 min. The same pattern of differences was observed for the
      affective response. The RPE during the seven weeks ranged from "fairly light" to
      "moderate" and the affective response from "good" to "very good." Thus, Tai Chi
      Chuan was perceived as a low-moderate intensity and pleasurable (positive affect)
      exercise by middle-aged and elderly women.

PMID- 25068756
TI  - Anthropometrics related to the performance of a sample of male swimmers.
AB  - The main purpose of the present investigation of 21 elite male swimmers was to
      assess whether the Ape Index (the ratio between the individual's arm span and
      height) and/or the second-to-fourth digit length ratio (2D:4D), i.e., the ratio
      between the length of the second and the fourth fingers of the right hand, are
      associated with the performance of high-level swimmers, when mood and/or
      executive function are covaried. The results showed no statistically significant
      correlation between the Ape Index and 2D:4D ratio, performance, executive
      function, or mood. In contrast, statistically significant correlations were found
      between 2D:4D ratio and performance, executive function, and mood. Regressions
      indicated that 2D:4D ratio and not Ape Index is related to the performances of a
      sample of male swimmers.

PMID- 25068758
TI  - Direct visualization of solid ordered domains induced by polyene antibiotics in
      giant unilamellar vesicles.
AB  - Polyene antibiotics isolated from Streptomyces are frequently used in treatment
      of mycoses. Confocal fluorescence microscopy has been employed to investigate the
      influence of polyene macrolide antibiotics nystatin, amphotericin B, and filipin
      on the phase separation in giant unilamellar vesicles. It has been demonstrated
      that nystatin produced the solid ordered domains in vesicles made from DOPC/Chol,
      DOPC/Chol/SM, and POPC while DOPC vesicles remained homogenous in the presence of
      polyene antibiotics. The ability of various polyenes to produce the solid ordered
      phase in POPC membranes has been compared. It has been shown that amphotericin B
      produced phase separation at lower concentration as compared with nystatin and
      filipin. Filipin was less effective in promotion of gel domains. The observed
      efficiency of polyene antibiotics to induce phase separation in lipid bilayers
      correlates with their biological activity. Present findings probably indicate the
      limitations of using of polyenes as fluorescence membrane probes for
      determination of strerol-enriched domains in plasma membrane of live cells. 

PMID- 25068759
TI  - A new Mucocutaneous Activity Index for Behcet's disease.
AB  - OBJECTIVES: Patient-reported outcomes are increasingly accepted to be major
      domains in chronic disorders. The aim of this study was to develop a patient
      derived disease activity index in Beh-cet's disease (BD). METHODS: One hundred
      and seventy-seven BD patients (M/F: 69/108) were included in the study. Data were
      collected by clinical examination and a questionnaire regarding a Mucocutaneous
      Index (MI) with genital ulcer activity (GI), erythema nodosum activity (EI) and
      the composite index (CI) for oral ulcers, as subscales of it. Self-reported
      treatment evaluation was carried out as criterion validity. Patients whose
      symptoms completely disappeared or decreased significantly, were categorised as
      'improved group', others were classified as 'non-improved group'. RESULTS: Among
      the study group, 79.7% of the patients (n=141) were active, whereas 20.3% were
      inactive (n=36). Scores of CI, GI, EI and MI score were 0+/-0 in inactive ones,
      whereas scores were 5.65+/-2.36 for CI, 0.81+/-2.34 for GI, 0.91+/-2.35 for EI
      and 6.25+/-5.1 for MI in actives (p=0.000 for all). MI score was significantly
      higher in 'non-improved group' (65.5%) compared to 'improved group' (34.5%)
      (p<0.0001). CONCLUSIONS: The mucocutaneous activity index may help decision
      making process for treatment strategies in BD patients.

PMID- 25068760
TI  - Ab initio study of charge transfer between lithium and aromatic hydrocarbons. Can
      the results be directly transferred to the lithium-graphene interaction?
AB  - We have used electronic density calculations to study neutral complexes of Li
      with aromatic hydrocarbons. The charge transferred between a Li atom and benzene,
      coronene, circumcoronene, and circumcircumcoronene has been studied by ab initio
      methods (at the HF and MP2 level). Toward this aim, the method of integrating
      electron density in two cuboid fragments of space was applied. One of the
      fragments was constructed so that it enclosed the bulk of the electron density of
      lithium; the second, the bulk of the electron density of hydrocarbon. It was
      found that for each complex two conformations were identified: the most stable
      with a greater vertical Li-hydrocarbon distance, on the order of 2.5 A, and
      another of higher energy with a corresponding distance less than 2 A. In all
      cases the transfer of a fractional number, 0.1-0.3 electrons, between Li and
      hydrocarbon was found; however, the direction of the transfer was not the same in
      all complexes investigated. The structures of complexes of the first
      configuration could be represented as Li(sigma-)...AH(sigma+), whereas the
      opposite direction of charge transfer was found for complexes of the second
      configuration, with higher energy. The directions of the dipole moments in the
      complexes supported these conclusions because they directly measure the
      redistribution of electron density in a complex with respect to substrates. 

PMID- 25068761
TI  - Analysis of the training load during a hypertrophy-type resistance training
      programme in men and women.
AB  - The purpose of this study was to analyze the specific training load during a
      resistance training (RT) programme designed to increase muscular hypertrophy in
      men and women. Thirty-four women (22.7 +/- 4.1 years, 58.8 +/- 11.9 kg, 162.6 +/-
      6.2 cm and 22.1 +/- 3.6 kg.m(-2)) and 30 men (22.7 +/- 4.4 years, 68.4 +/- 9.0
      kg, 174.5 +/- 6.6 cm and 22.5 +/- 2.4 kg.m(-2)) underwent a supervised RT
      programme that was divided into two phases of 8 weeks each. Training consisted of
      10-12 exercises performed with three sets of 8-12 repetitions at repetition
      maximum resistances performed 3 times per week on nonconsecutive days. There was
      a significant (P < 0.05) main effect for gender by time interaction for average
      training load of all the exercises performed in the first 8 weeks of RT with
      women showing a higher relative increase than men (+43.6% vs. +32.5%,
      respectively). This result was not observed during the second 8-week phase of the
      RT programme during which no significant gender by time interaction (P > 0.05)
      was shown with both genders having a similar relative increase (+28.7% vs.
      +24.3%, respectively). Women had a higher increase than men in specific average
      training load of the upper limb exercises during both the first 8 weeks of
      training (+30.2% vs. +26.6%, respectively) and the second 8 weeks of training
      (+31.1% vs. +25.3%, respectively). We conclude that the adaptation in specific
      training load is influenced by gender. 

PMID- 25068762
TI  - Postage stamp-sized array sensor for the sensitive screening test of heavy-metal
      ions.
AB  - The sensitive determination of heavy-metal ions has been widely investigated in
      recent years due to their threat to the environment and to human health. Among
      various analytical detection techniques, inexpensive colorimetric testing
      papers/strips play a very important role. The limitation, however, is also clear:
      the sensitivity is usually low and the selectivity is poor. In this work, we have
      developed a postage stamp-sized array sensor composed of nine commercially
      available heterocyclic azo indicators. Combining filtration-based enrichment with
      an array of technologies-based pattern-recognition, we have obtained the
      discrimination capability for seven heavy-metal ions (Hg(2+), Pb(2+), Ag(+),
      Ni(2+), Cu(2+), Zn(2+), and Co(2+)) at their Chinese wastewater discharge
      standard concentrations. The allowable detection level of Hg(2+) was down to 0.05
      mg L(-1). The heavy-metal ions screening test was readily achieved using a
      standard chemometric approach. And the array sensor applied well in real water
      samples. 

PMID- 25068763
TI  - Rituximab and tocilizumab for the treatment of rheumatoid arthritis.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of
      rituximab and tocilizumab compared with adalimumab, etanercept, and infliximab,
      in patients with rheumatoid arthritis not responding to first-line treatment, and
      to compare the efficacy and safety of rituximab versus tocilizumab in patients
      not responding to anti-tumor necrosis factor alpha (anti-TNF) therapy. METHODS: A
      literature search of randomized controlled trials, controlled clinical trials,
      and systematic reviews was performed to evaluate efficacy and safety of rituximab
      and tocilizumab. RESULTS: Twenty-four RCTs were included in this systematic
      review with 6,357 participants; 3,450 treated with biological DMARD and 2,907
      with standard care. In patients not responding to first-line treatment, rituximab
      shows lower response rate in at least 50 percent improvement in the American
      College of Rheumatology criteria (ACR50) and ACR70 compared with etanercept, at 6
      months of follow-up. Tocilizumab shows higher ACR70 response rate compared with
      infliximab, at the same follow-up time. Other results showed no significant
      differences. Indirect comparisons between rituximab and tocilizumab in patients
      not responding for at least one anti-TNF, shows higher ACR20 response rate for
      tocilizumab at 6 months of follow-up. Regarding safety, adalimumab and etanercept
      were associated with significant fewer withdrawals due to adverse events compared
      with infliximab. CONCLUSIONS: Considering efficacy, safety, and the availability
      of 3 anti-TNFs in the National Medicines Formulary (adalimumab, etanercept, and
      infliximab), it seems appropriate to remove infliximab from the coverage, and
      introduce tocilizumab for patients not responding for at least one anti-TNF.

PMID- 25068764
TI  - Branch-selective allylic C-H carboxylation of terminal alkenes by Pd/sox
      catalyst.
AB  - A ligand-controlled branch-selective allylic C-H carboxylation through Pd
      catalysis is described. The developed catalytic system, which consists of
      Pd(OAc)2, sulfoxide-oxazoline (sox) as a ligand and benzoquinone as an oxidant,
      couples terminal alkenes and carboxylic acids to furnish the corresponding
      branched allylic esters with high regioselectivity. 

PMID- 25068765
TI  - Functional group transformations in derivatives of 1,4
      dihydrobenzo[1,2,4]triazinyl radical.
AB  - Transformations of functional groups OCOPh, OCH2Ph, I, NO2, and CO2Me in
      Blatter's radical derivatives 1-5 were investigated in order to develop synthetic
      tools for incorporation of the benzo[1,2,4]triazinyl system into complex
      molecular architectures. Thus, basic hydrolysis of OCOPh or Pd-catalyzed
      debenzylation of OCH2Ph gave phenol functionality, which was acylated and
      alkylated. Pd-catalyzed Suzuki, Negishi, Sonogashira, and Heck C-C cross-coupling
      reactions of iodo derivatives 1c, 1d, and 2d were also successful and efficient.
      Reduction of NO2 in 1e led to aniline derivative 1t, which was reductively
      alkylated with hexanal and coupled to l-proline. Selected benzo[1,2,4]triazinyl
      radicals were characterized by EPR and electronic absorption spectroscopy, and
      the results were analyzed in tandem with DFT computational methods. Lastly, the
      mechanism for formation of the 1,4-dihydrobenzo[1,2,4]triazine ring was
      investigated using the B3LYP/6-31G(2d,p) method. 

PMID- 25068766
TI  - Amphiphilic self-assembly of alkanols in protic ionic liquids.
AB  - Strong cohesive forces in protic ionic liquids (PILs) can induce a liquid
      nanostructure consisting of segregated polar and apolar domains. Small-angle X
      ray scattering has shown that these forces can also induce medium chain length n
      alkanols to self-assemble into micelle- and microemulsion-like structures in
      ethylammonium (EA(+)) and propylammonium (PA(+)) PILs, in contrast to their
      immiscibility with both water and ethanolammonium (EtA(+)) PILs. These binary
      mixtures are structured on two distinct length scales: one associated with the
      self-assembled n-alkanol aggregates and the other with the underlying liquid
      nanostructure. This suggests that EA(+) and PA(+) enable n-alkanol aggregation by
      acting as cosurfactants, which EtA(+) cannot do because its terminating hydroxyl
      renders the cation nonamphiphilic. The primary determining factor for miscibility
      and self-assembly is the ratio of alkyl chain lengths of the alkanol and PIL
      cation, modulated by the anion type. These results show how ILs can support the
      self-assembly of nontraditional amphiphiles and enable the creation of new forms
      of soft matter. 

PMID- 25068767
TI  - The evaluation of anxiety and depression status in spouses of sexually active
      reproductive women with fibromyalgia.
AB  - OBJECTIVES: Fibromyalgia (FM) can cause neuropsychiatric symptoms and sexual
      dysfunction. However, no data exist regarding anxiety and depression status in
      spouses of sexually active women with FM. Accordingly, we aimed to evaluate
      whether emotional status are affected in spouses of women with FM, and to search
      whether there was a relationship between sexual dysfunction of women with FM and
      emotional status of their spouses. METHODS: Thirty newly diagnosed, never treated
      reproductive women with FM and 30 age-matched healthy women as well as their
      spouses were included. Psychological status was evaluated using Beck
      depression/anxiety inventory (BDI/BAI). Sexual function was evaluated using
      Female Sexual Function Index (FSFI) and Index of Female Sexual Function (IFSF).
      RESULTS: BDI, BAI, FSFI and IFSF scores were significantly higher in women with
      FM than in controls. The spouses of women with FM had increased BDI and BAI
      scores as compared to spouses of controls (7.10 +/- 7.76 vs. 2.10 +/- 2.68, 6.96
      +/- 6.62 vs. 2.20 +/- 3.16, respectively, p<0.001). BDI scores of women with FM
      significantly correlated to BDI scores of their spouses, but there was no
      significant relationship between BDI scores of spouses and sexual functions of
      women with FM. CONCLUSIONS: FM can cause deterioration of emotional status and
      lead to sexual dysfunction. Also, psychological status could be affected in
      spouses of women with FM at reproductive age, and the severity of depression of
      their spouses was significantly correlated to that of women with FM. However,
      this affection in psychological status did not relate to sexual problems of the
      women with FM.

PMID- 25068768
TI  - Slanted medial rectus recession is effective in the treatment of convergence
      excess esotropia.
AB  - PURPOSE: To evaluate the surgical outcomes of slanted medial rectus recession in
      patients diagnosed as having convergence excess esotropia. METHODS: Bilateral
      slanted recession of medial rectus muscles was performed in 16 patients with
      convergence excess esotropia. The lower margins of medial rectus muscles were
      recessed 1 to 2 mm more than the upper margins. Changes in near-distance
      disparity of the deviations were recorded. RESULTS: The mean preoperative near
      distance disparity of 20.3+/-6.5 prism diopters (PD) decreased to 4.37+/-5.6 PD
      postoperatively. The amount of collapse was significant (mean: 16 PD; P<.005).
      Near-distance disparity of 10 PD or less was obtained in 14 patients after
      surgery (87.5%), except 2 patients who had 16 PD of disparity. The authors did
      not encounter overcorrection except in 1 patient in whom minimal exophoria at
      distance and near with the glasses was observed and reduced the prescription.
      CONCLUSIONS: Bilateral slanted medial rectus muscle recession procedure
      effectively decreases the disparity between near and distance deviations in
      patients with convergence excess esotropia.

PMID- 25068769
TI  - Physical activity and hypothalamic-pituitary-adrenocortical axis function in
      adolescents.
AB  - Little is known about the associations between physical activity (PA) and
      hypothalamic-pituitary-adrenocortical axis (HPAA) activity in adolescents. This
      knowledge could offer insight into the links between PA and well-being in youth.
      We studied whether objectively-measured PA is associated with diurnal salivary
      cortisol responses and morning salivary cortisol responses after a low-dose
      overnight dexamethasone suppression test (DST) in adolescent girls and boys. We
      conducted a cross-sectional birth cohort study in Helsinki, Finland. At a mean
      age of 12.4 (SD=0.5) years, 150 girls and 133 boys wore wrist-worn accelerometers
      over at least 4 days to measure PA. Their salivary cortisol was measured across 1
      day and upon awakening after a low-dose overnight DST (3 MUg/kg of weight). Girls
      with higher overall PA and vigorous PA (VPA), and less sedentary time had lower
      salivary cortisol upon awakening and/or after (decreases between |0.17| and
      |0.25| SDs per SD increase in overall PA, VPA and decrease in sedentary time; P
      values<0.039). Boys with higher overall PA, and less sedentary time had greater
      suppression of salivary cortisol following overnight DST (suppression between
      |0.24| and |0.27| SDs per SD increase in overall PA and decrease in sedentary
      time; P-values<0.012). Overall PA, VPA and sedentary time did not associate with
      DST suppression in girls or with diurnal salivary cortisol in boys. These results
      show that PA is associated with altered HPAA function in early adolescents, and
      that the associations are sex specific.

PMID- 25068770
TI  - A bifunctional Cr/Yb/Tm:Ca3Ga2Ge3O12 phosphor with near-infrared long-lasting
      phosphorescence and upconversion luminescence.
AB  - Currently, upconversion nanocrystals and long-lasting phosphorescent particles
      have attracted extensive research interest for their possible applications as
      bioimaging probes. However, there are few reports concerning the achievement of
      both upconversion luminescence of lanthanide ions and long-lasting
      phosphorescence of transition metal ions in a sole host so far. Herein, we
      demonstrate a novel calcium gallium germanium garnet (Ca3Ga2Ge3O12) host where
      lanthanide ions such as Tm(3+)/Yb(3+) and transition metal ions such as Cr(3+)
      can be easily incorporated through substituting the Ca(2+) and Ga(3+)
      respectively. This Cr/Yb/Tm:Ca3Ga2Ge3O12 phosphor exhibits both broadband near
      infrared long-lasting phosphorescence of Cr(3+) with an afterglow time of more
      than 7000 s and near-infrared to near-infrared upconversion luminescence of
      Tm(3+). Impressively, it is evidenced that the addition of Yb(3+)/Tm(3+) into
      Cr:Ca3Ga2Ge3O12 not only results in Tm(3+) upconversion luminescence but also
      greatly increases Cr(3+) afterglow time. Based on excitation/emission, three
      dimensional thermoluminescence, and time-resolved luminescence spectra, the
      related long-lasting phosphorescence and upconversion luminescent mechanisms are
      systematically discussed as well. 

PMID- 25068771
TI  - Is warm or cold Calafiore blood cardioplegia better? Hemodynamic, metabolic, and
      electron microscopic differences.
AB  - BACKGROUND: Controversy exists as to whether warm or cold Calafiore blood
      cardioplegia (BCP) is better for cardiac preservation. Therefore, we compared
      hemodynamic performance, myocardial metabolism, and ultrastructural preservation
      in rat hearts after application of cold or warm BCP. MATERIALS AND METHODS: The
      hearts of 24 male Wistar rats were excised and inserted into a blood perfused
      isolated heart apparatus, and after a stabilization period of 30 minutes, either
      cold (4 degrees C) or warm (36 degrees C) Calafiore BCP was administered during
      an aortic clamping time of 90 minutes (12 rats each). Hearts clamped without BCP
      and hearts immediately excised in anesthesia served as worst case and no damage
      controls, respectively (n=3 each). During reperfusion, functional hemodynamic
      parameters were recorded in BCP groups, and myocardial oxygen consumption and
      lactate production were calculated. After perfusion fixation, the hearts of three
      rats in each group were investigated for cellular edema and mitochondrial damage
      by morphometry using transmission electron microscopy. RESULTS: Cardiac function
      after BCP application during aortic clamping showed a slightly better recovery
      with warm than with cold Calafiore BCP as indicated by higher left ventricular
      developed pressure (warm 97% of baseline, cold 68% of baseline) after warm BCP.
      Other hemodynamic parameters and coronary flow were not different between warm
      and cold BCP. Myocardial oxygen consumption and lactate production were similar
      under warm and cold conditions. Electron microscopy showed typical signs of
      ischemia in the ischemia group without BCP. Mitochondrial ultrastructure was well
      preserved in both BCP groups, but cellular edema was more pronounced with cold
      than with warm BCP. The qualitative analysis was confirmed by the morphometric
      cellular edema index and the volume-to-surface ratio of the mitochondria.
      CONCLUSION: Only mild differences were observed between warm and cold BCP in rats
      with respect to cardiac function, metabolism, and tissue preservation after
      aortic clamping. However, a small tendency toward better postischemic recovery
      was observed with warm BCP.

PMID- 25068772
TI  - Incidence of drug interaction when using proton pump inhibitor and warfarin
      according to cytochrome P450 2C19 (CYP2C19) genotype in Japanese.
AB  - OBJECTIVES: The US Food and Drug Administration has suggested that proton pump
      inhibitors (PPIs) increase the international normalized ratio (INR) when used
      concomitantly with warfarin (WF) because of being metabolized by cytochrome P450
      2C19 (CYP2C19). We assessed whether CYP2C19 genotypes and type of PPI accentuated
      the drug interaction. METHODS AND RESULTS: The study group was 82 patients who
      needed WF after surgery and had their CYP2C19 genotypes analyzed in advance. We
      randomly divided them into two groups: group I (n = 41) included patients who had
      lansoprazole 15 mg/day and group II (n = 41) included patients who had
      rabeprazole 10 mg/day. The dose of WF was controlled by the doctor in charge as a
      target INR of 1.6 to 2.6 during the 2 months after surgery. The maximum INR was
      significantly higher in group I (3.36 +/- 0.98) than in group II (2.29 +/- 0.55,
      p < 0.0001). The incidence of over-INR (> 3.5) was significantly higher in group
      I (15 cases) than in group II (2 cases, p = 0.0001). Several bleeding events
      complicated 10 patients in group I, but none in group II (p = 0.015). Logistic
      regression analysis revealed that over-INR (odds ratio [OR] 3.58, 95% confidence
      interval [CI]: 3.48-368.25, p < 0.0001), and pair of lansoprazole and CYP2C19
      intermediate metabolizer (OR 2.39, 95% CI: 1.108-29.491, p = 0.0009) were
      independent predictors of bleeding events. CONCLUSION: If a patient has had the
      intermediate metabolizer CYP2C19 genotype and concomitant use of WF and a PPI
      after open heart surgery, lansoprazole intensifies the effects of WF and is
      associated with bleeding events.

PMID- 25068773
TI  - Perioperative Outcomes after Lung Resection in Obese Patients.
AB  - BACKGROUND: Obesity is a growing epidemic in the developed world. However, little
      is known about the impact of obesity on the perioperative morbidity and mortality
      after lung resection. PATIENTS AND METHODS: We analyzed the American College of
      Surgeons National Surgical Quality Improvement Program database from 2005 to 2010
      to determine whether obesity is a risk factor for perioperative morbidity and
      mortality after pulmonary resection. Demographic, clinical, intraoperative, and
      morbidity and mortality data were collected. Multivariable predictors of
      morbidity and mortality were determined using regression analysis. RESULTS: A
      total of 5,216 lung resections were identified (1,372 wedges, 3,713 lobectomies,
      and 131 pneumonectomies). The median age was 66 years and 2,587 (49.6%) were
      females. The body mass index (BMI, kg/m(2)) of the patients was as follows: 192
      (3.7%) < 18.5; 1,727 (33.1%) 18.5 to 24.9; 1,754 (33.6%) 25 to 29.9; and 1,488
      (28.5%) > 30. In-hospital mortality and all-cause morbidity was 2.4% (n = 127)
      and 14.5% (n = 757) for the entire cohort of patients, respectively. BMI was not
      found to be a predictor of increased mortality or morbidity, even in the morbidly
      obese (BMI > 35). Rather, age, approach (video-assisted thoracoscopic surgery vs.
      open), parameters assessing performance status, operative time, and preoperative
      radiation therapy were the predictors of morbidity and mortality. Conversely,
      being overweight (BMI 25-30) approached significance as a multivariate predictor
      for decreased pulmonary complications (odds ratio, 0.77 [0.592-1.004]; p = 0.054)
      consistent with the "obesity paradox" observed after nonbariatric general
      surgery. CONCLUSION: Our large national study shows that obesity does not
      negatively impact perioperative mortality and morbidity in patients undergoing
      lung resection. Surgical resections should not be denied to obese (BMI > 30)
      patients.

PMID- 25068774
TI  - Thoracic Wall Reconstruction with Acellular Porcine Dermal Collagen Matrix.
AB  - BACKGROUND:  Major thoracic wall resections require the implantation of foreign
      materials for reconstruction and stabilization. Recently, biological collagen
      matrixes have emerged as an alternative to the routinely used synthetic
      materials. MATERIALS AND METHODS:  Retrospectively, we analyzed our initial
      experience of chest wall reconstruction on large defects using a cross-linked
      porcine dermal acellular collagen matrix mesh with a thickness of 1.5 mm.
      RESULTS:  Six sarcoma patients with a mean age of 46 (22-66) years underwent
      chest wall resections. Complete thoracic wall defects (mean area 149 cm2) ranged
      from 8 * 10 to 15 * 20 cm in size. In the majority of cases, only mobilized
      subcutaneous tissue and skin were used for soft-tissue coverage of the implanted
      porcine collagen matrix patches. Implantation and postoperative courses were
      uneventful in all patients. No local infections or wound healing problems
      occurred. The collagen material resulted in durable and good to excellent chest
      wall stability in clinical follow-ups, and on computed tomography scans spanning
      over 3.5 years. Histological examination showed integration, neovascularization,
      and long-term persistence of the collagen matrix on late reoperation of one
      patient. CONCLUSION:  Acellular porcine dermal collagen matrix is a feasible and
      reliable biological patch material for reconstruction of the thoracic wall.
      Excellent wound healing and long-term stability are achieved even in large
      defects or complete sternal replacements.

PMID- 25068775
TI  - The Role of Maximum Standardized Uptake Value in PET/CT as a Prognostic Factor in
      Patients with Resected Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the role of the maximum
      standardized uptake value (mSUV) of the main mass as a risk factor for recurrence
      in patients with completely resected esophageal squamous cell carcinoma (ESCC).
      PATIENTS AND METHODS: Clinicopathologic factors including primary tumor location,
      tumor size, depth of tumor invasion, number of positive lymph nodes,
      angiolymphatic invasion, and mSUV were analyzed as risk factors for recurrence.
      The prognostic influence of variables on disease-free survival was analyzed using
      the log-rank test for univariate analysis and the Cox proportional hazards model
      for multivariate analysis. RESULTS: A total of 102 patients underwent complete
      resection of ESCC and positron emission tomography/computed tomography was
      performed. The median follow-up period was 35.0 months (range, 2-94). The average
      mSUV of the main mass was 5.5 +/- 4.2. The tumor had recurred in 38 patients
      (37.3%). Univariate analysis identified that tumor size (> 3.5 cm), depth of
      tumor invasion (>= T2), pathologic stage, and mSUV (> 5.1) were statistically
      significant prognostic factors for recurrence of ESCC. However, in multivariate
      analysis, only mSUV (> 5.1, HR = 4.222, p = 0.025) was the independent risk
      factor of recurrence. CONCLUSIONS: The mSUV of the main mass was an independent
      predictor for recurrence with a cutoff value of 5.1.

PMID- 25068777
TI  - Clinical indications for implantation of the total artificial heart.
AB  - The total artificial heart (TAH) is effective for bridging patients with
      biventricular heart failure (BiVHF) to transplantation. It consists of two
      pneumatic pumps with four mechanical valves that replace nearly the entire
      myocardium, thus also making it effective therapy for heart failure from
      alternative (ALT) anatomical and pathophysiological causes that preclude left
      ventricular assist device (LVAD). This report reviews the clinical indications
      and outcomes for TAH implantation at our institution from 2006 to 2012. We sought
      to characterize and compare survival to transplant for patients with BiVHF to
      those with ALT indications. The overall survival to transplant for all patients
      was 86% (57/66). There was a trend towards decreased survival to transplantation
      in the ALT group compared with the BiVHF group (77% vs. 93%, HR 0.42 [95%
      confidence interval 0.1, 1.7], log-rank test: p = 0.2). This was likely driven by
      certain high risk subgroups of allograft failure, LVAD failure, and acute
      postinfarct shock. 

PMID- 25068776
TI  - Short- and Mid-Term Changes in Lung Function after Bilateral Pulmonary
      Metastasectomy.
AB  - INTRODUCTION: The resection of pulmonary metastases is associated with a loss of
      lung function. The amount of functional impairment after bilateral metastasectomy
      remains unclear. Because only around 35% of those patients may expect long-term
      survival, it is important to preserve enough pulmonary function for an adequate
      quality of life. This analysis of 31 bilaterally operated patients was performed
      to describe the amount of pulmonary function loss. METHODS: This is a post-hoc
      subanalysis and comparison of a population that was published before. All
      pulmonary metastasectomies were performed through an anteroaxillary thoracotomy
      in all patients. Resections were performed with staplers, electrocautery, or
      laser. All patients had pulmonary function tests (PFTs) preoperative and after 3
      months at the follow-up visit, including spirometry, diffusing capacity of lung
      for carbon monoxide (Dlco) and blood gases. Of the 31 bilaterally operated cases,
      15 had additional PFTs after each staged operation before discharge from
      hospital. RESULTS: Altogether, 271 nodules (median 7, mean 8.2) were removed from
      the 31 patients with a lobectomy in 2, a segmentectomy in 8, and multiple wedge
      resections in 21 patients, with this being the largest resection. The mean loss
      of pulmonary function at follow-up visit was forced vital capacity (FVC) - 15.2%,
      total lung capacity (TLC) - 13.8%, forced expiratory volume in 1 second (FEV1) -
      16.3%, and Dlco - 10.3%, all of which were significant (p = < 0.001). The 15
      patients with PFTs after each operation showed a stepwise decrease of volume
      parameters and Dlco with deepest values after the second surgery of around - -40%
      from preoperative values. At this time, Po 2 was also significantly reduced by 10
      mm Hg (p = 0.01). Comparing the bilateral group with 86 patients after unilateral
      metastasectomy, we found significantly more nodules removed in the bilateral
      group (8.2 vs. 3.1; p < 0.001) and that the loss of volume parameters was twice
      that of the unilateral group after metastasectomy. Dlco impairment did not differ
      between the groups (- 10.3 vs. - 9.5%; p = 0.868) after 3 months. CONCLUSION:
      Midterm pulmonary function impairment after bilateral pulmonary metastasectomy is
      15% of spirometry values and 10% of Dlco. Reduction of spirometry values is
      almost twice compared with the group after unilateral surgery. Early functional
      loss after the second intervention causes FVC, TLC, and FEV1 reduction of around
      40% and is associated with lower Po 2 (- 10 mm Hg). Therefore, bilateral
      metastasectomy can be offered to patients who do not have greater pulmonary
      limitations.

PMID- 25068779
TI  - Association of HeartMate II left ventricular assist device flow estimate with
      thermodilution cardiac output.
AB  - Cardiac output (CO) assessment is important in treating patients with heart
      failure. Durable left ventricular assist devices (LVADs) provide essentially all
      CO. In currently used LVADs, estimated device flow is generated by a computerized
      algorithm. However, LVAD flow estimate may be inaccurate in tracking true CO. We
      correlated LVAD (HeartMate II) flow with thermodilution CO during postoperative
      care (day 2-10 after implant) in 81 patients (5,616 paired measurements). Left
      ventricular assist device flow and CO correlated with a low correlation
      coefficient (r = 0.42). Left ventricular assist device readings were lower than
      CO measurements by approximately 0.36 L/min, trending for larger difference with
      higher values. Left ventricular assist device flow measurements showed less
      temporal variability compared with CO. Grouping for simultaneous measured blood
      pressure (BP < 60, 60-70, 70-80, 80-90, and >=90), the correlation of CO with
      LVAD flow differed (R = 0.42, 0.67, 0.48, 0.32, 0.32, respectively). Indicating
      better correlation when mean blood pressure is 60 to 70 mm Hg. Left ventricular
      assist device flow generally trends with measured CO, but large variability
      exists, hence flow measures should not be assumed to equal with CO. Clinicians
      should take into account variables such as high CO, BP, and opening of the aortic
      valve when interpreting LVAD flow readout. Direct flow sensors incorporated in
      the LVAD system may allow for better estimation. 

PMID- 25068780
TI  - A qualitative investigation of low-income abortion clients' attitudes toward
      public funding for abortion.
AB  - We explored how low-income abortion clients in states where public funding was
      and was not available perceived the role of public funding for abortion. From
      October 2010 through February 2011, we conducted 71 semi-structured in-depth
      telephone interviews with low-income abortion clients in Arizona, Florida, New
      York, and Oregon. Women reported weighing numerous factors when determining which
      circumstances warranted public funding. Though most women generally supported
      coverage, they deviated from their initial support when asked about particular
      circumstances. Respondents felt most strongly that abortion should not be covered
      when a woman could not afford another child or was pregnant outside of a romantic
      relationship. Participants used disparaging language to describe the presumed
      behavior of women faced with unintended pregnancies. In seeking to discredit
      "other" women's abortions, women revealed the complex nature of abortion stigma.
      We propose that women's abortion experiences and subsequent opinions on coverage
      indicated three distinct manifestations of abortion stigma: women (1) resisted
      the prominent discourse that marks women who have had abortions as selfish and
      irresponsible; (2) internalized societal norms that stereotype women based on the
      circumstances surrounding the abortion; and (3) reproduced stigma by distancing
      themselves from the negative stereotypes associated with women who have had
      abortions.

PMID- 25068781
TI  - Synthesis, characterization and in vitro antitumor activity of platinum(II)
      oxalato complexes involving 7-azaindole derivatives as coligands.
AB  - The platinum(II) oxalato complexes [Pt(ox)(naza)2] (1-3) were synthesized and
      characterized by elemental analysis (C, H, N), multinuclear NMR spectroscopy
      ((1)H, (13)C, (15)N, (195)Pt) and electrospray ionization mass spectrometry (ESI
      MS); naza = 4-chloro-7-azaindole (4Claza; 1), 3-bromo-7-azaindole (3Braza; 2) or
      4-bromo-7-azaindole (4Braza; 3). The prepared substances were screened for their
      in vitro antitumor activity on the osteosarcoma (HOS) and breast adenocarcinoma
      (MCF7) human cancer cell lines, where 2 showed moderate antitumor effect (IC50 =
      27.5 MUM, and 18.3 MUM, respectively). The complex 2 was further tested on a
      panel of six others human cancer cell lines, including the malignant melanoma
      (G361), cervix carcinoma (HeLa), ovarian carcinoma (A2780), cisplatin-resistant
      ovarian carcinoma (A2780R), lung carcinoma (A549) and prostate adenocarcinoma
      (LNCaP). This substance was found to be moderate antitumor effective against G361
      (IC50 = 17.3 MUM), HeLa (IC50 = 31.8 MUM) and A2780 (IC50 = 19.2 MUM) cell lines.
      The complex 2 was also studied by NMR for its solution stability and by ESI-MS
      experiments for its ability to interact with biomolecules, such as cysteine,
      glutathione or guanosine 5'-monophosphate.

PMID- 25068782
TI  - Desorption of water from distinct step types on a curved silver crystal.
AB  - We have investigated the adsorption of H2O onto the A and B type steps on an Ag
      single crystal by temperature programmed desorption. For this study, we have used
      a curved crystal exposing a continuous range of surface structures ranging from
      [5(111) * (100)] via (111) to [5(111) * (110)]. LEED and STM studies verify that
      the curvature of our sample results predominantly from monoatomic steps. The
      sample thus provides a continuous array of step densities for both step types.
      Desorption probed by spatially-resolved TPD of multilayers of H2O shows no
      dependence on the exact substrate structure and thus confirms the absence of
      thermal gradients during temperature ramps. In the submonolayer regime, we
      observe a small and linear dependence of the desorption temperature on the A and
      B step density. We argue that such small differences are only observable by means
      of a single curved crystal, which thus establishes new experimental benchmarks
      for theoretical calculation of chemically accurate binding energies. We propose
      an origin of the observed behavior based on a "two state" desorption model. 

PMID- 25068783
TI  - Characterization and antitumor activity of a polysaccharide from Sarcodia
      ceylonensis.
AB  - A water-soluble polysaccharide from Sarcodia ceylonensis was obtained by using
      the method of water-extraction and ethanol-precipitation. The polysaccharide was
      further purified by chromatography on AB-8 and ADS-7 columns, yielding a pure
      polysaccharide termed SCP-60. The molecular weight (Mw) of SCP-60 was calculated
      to be 50.0 kDa, based on the calibration curve obtained with a series of Dextran
      T standards. The results of FT-IR indicated that the polysaccharide contains the
      alpha-configuration of sugar units. GC-MS analysis revealed that SCP-60 was
      mainly composed of galactose and glucose. NMR spectroscopy revealed SCP-60 had
      the backbone consisting of -> 6)-alpha-Manp-(1 ->, alpha-D-Glcp-(1 ->, -> 6)
      alpha-D-Glcp-(1 -> and -> 6)-alpha-Galp-(1 ->. In order to evaluate the antitumor
      activity in vivo of the polysaccharide, a sarcoma 180 model was used. The results
      showed SCP-60 had strong antitumor ability, meanwhile, SCP-60 at a high dose (100
      mg/kg) could significantly increase the thymic and splenic indices of S180 mice,
      and strongly promote the secretion of IL-2, TNF-alpha and IFN-gamma, increase the
      SOD activities and reduce the concentrations of MDA in blood. Therefore the
      polysaccharide SCP-60 should be explored as a novel potential antitumor drug.

PMID- 25068784
TI  - ROS-dependent antiproliferative effect of brassinin derivative homobrassinin in
      human colorectal cancer Caco2 cells.
AB  - This study was designed to examine the in vitro antiproliferative effect of
      brassinin and its derivatives on human cancer cell lines. Among seven tested
      compounds, homobrassinin (K1; N-[2-(indol-3-yl)ethyl]-S-methyldithiocarbamate)
      exhibited the most potent activity with IC50 = 8.0 MUM in human colorectal Caco2
      cells and was selected for further studies. The flow cytometric analysis revealed
      a K1-induced increase in the G2/M phase associated with dysregulation of alpha
      tubulin, alpha1-tubulin and beta5-tubulin expression. These findings suggest that
      the inhibitory effect of K1 can be mediated via inhibition of microtubule
      formation. Furthermore, simultaneously with G2/M arrest, K1 also increased
      population of cells with sub-G1 DNA content which is considered to be a marker of
      apoptotic cell death. Apoptosis was also confirmed by annexin V/PI double
      staining, DNA fragmentation assay and chromatin condensation assay. The apoptosis
      was associated with the loss of mitochondrial membrane potential (MMP), caspase-3
      activation as well as intracellular reactive oxygen species (ROS) production.
      Moreover, the antioxidant Trolox blocked ROS production, changes in MMP and
      decreased K1 cytotoxicity, which confirmed the important role of ROS in cell
      apoptosis. Taken together, our data demonstrate that K1 induces ROS-dependent
      apoptosis in Caco2 cells and provide the rationale for further in vivo anticancer
      investigation. 

PMID- 25068785
TI  - Dereplication guided discovery of secondary metabolites of mixed biosynthetic
      origin from Aspergillus aculeatus.
AB  - Investigation of the chemical profile of the industrially important black
      filamentous fungus Aspergillus aculeatus by UHPLC-DAD-HRMS and subsequent
      dereplication has led to the discovery of several novel compounds. Isolation and
      extensive 1D and 2D NMR spectroscopic analyses allowed for structural elucidation
      of a dioxomorpholine, a unique okaramine, an aflavinine and three novel
      structures of mixed biosynthetic origin, which we have named aculenes A-C.
      Moreover, known analogues of calbistrins, okaramines and secalonic acids were
      detected. All novel compounds were tested for antifungal activity against Candida
      albicans, however all showed only weak or no activity. Aspergillus aculeatus IBT
      21030 was additionally shown to be capable of producing sclerotia. Examination of
      the sclerotia revealed a highly regulated production of metabolites in these
      morphological structures. 

PMID- 25068786
TI  - Accumulation of astragalosides and related gene expression in different organs of
      Astragalus membranaceus Bge. var mongholicus (Bge.).
AB  - Astragalus membranaceus is one of the most important traditional Korean and
      Chinese medicinal herbs because it contains triterpenoid saponins (astragaloside
      I, II, III, and IV), which have beneficial and pharmacological effects on health.
      In this study, we analyzed 10 mevalonate pathway genes that are involved in
      astragaloside biosynthesis using the Illumina/Solexa HiSeq2000 platform. We
      determined the expression levels of the 10 genes using quantitative real-time
      PCR, and analyzed the accumulation of astragalosides in different organs using
      high-performance liquid chromatography. Genes related to the mevalonate pathway
      were expressed in different levels in different organs. Almost all genes showed
      high transcript levels in the stem and leaf, with the lowest transcript levels
      being recorded in the root. In contrast, most astragalosides accumulated in the
      root. In particular, the astragaloside IV content was distributed in the
      following order: root (0.58 mg/g DW) > flower (0.27 mg/g DW) > stem (0.23 mg/g
      DW) > leaf (0.04 mg/g DW). In the root, astragaloside II exhibited the highest
      content (2.09 mg/g DW) compared to astragaloside I, III, and IV. Notably, gene
      expression did not follow the same pattern as astragaloside accumulation. We
      suggest carefully that astragalosides are synthesized in the leaves and stem and
      then translocated to the root. This study contributes towards improving our
      understanding of astragaloside biosynthesis in A. membranaceus. 

PMID- 25068788
TI  - Establishment of a new murine elastase-induced aneurysm model combined with
      transplantation.
AB  - INTRODUCTION: The aim of our study was to develop a reproducible murine model of
      elastase-induced aneurysm formation combined with aortic transplantation.
      METHODS: Adult male mice (n = 6-9 per group) underwent infrarenal, orthotopic
      transplantation of the aorta treated with elastase or left untreated.
      Subsequently, both groups of mice were monitored by ultrasound until 7 weeks
      after grafting. RESULTS: Mice receiving an elastase-pretreated aorta developed
      aneurysms and exhibited a significantly increased diastolic vessel diameter
      compared to control grafted mice at 7 week after surgery (1.11 +/- 0.10 mm vs.
      0.75 +/- 0.03 mm; p <= 0,001). Histopathological examination revealed disruption
      of medial elastin, an increase in collagen content and smooth muscle cells, and
      neointima formation in aneurysm grafts. CONCLUSIONS: We developed a reproducible
      murine model of elastase-induced aneurysm combined with aortic transplantation.
      This model may be suitable to investigate aneurysm-specific inflammatory
      processes and for use in gene-targeted animals.

PMID- 25068789
TI  - Dietary factors as the major determinants of overweight and obesity among Iranian
      adolescents. A cross-sectional study.
AB  - This study investigated the determinants of overweight/obesity in adolescents. A
      cross-sectional survey was carried out on 1157 adolescents. Weight and height
      were measured. Information on socio-economic status (SES), dietary intakes,
      physical activity, and sedentary behaviours were collected by a self-administered
      questionnaire. Binary and multivariate binary logistic regressions were used to
      obtain the relationships and odds-ratios, respectively. The prevalence of
      overweight and obesity was higher among adolescents in low- or high-income
      families, adolescents whose mothers worked out of home, adolescents whose parents
      were both overweight, adolescents who watched a lot of TV or had excessive energy
      intake, adolescents with lower physical activity or lower intake of dietary
      fibre, those who skipped breakfast >= 4 times per week, and those with low and
      high fat intake. However, multiple logistic regression analysis showed that only
      energy intake was associated with increased odds and vegetables and fibre intake
      were associated with a reduction in the odds of being overweight (all p<0.05).
      Adolescents from middle SES showed a lower risk of overweight/obesity than low
      and high SES due to better dietary intakes and less sedentary behaviours.
      Therefore, in overweight/obesity prevention programs, adolescents with determined
      risk factors from families with low and high SES should receive attention.

PMID- 25068790
TI  - Effects of vitamin E supplementation on exercise-induced oxidative stress: a meta
      analysis.
AB  - Tocopherols (commonly referred to as "vitamin E") are frequently studied
      antioxidants in exercise research. However, the studies are highly heterogeneous,
      which has resulted in contradicting opinions. The aim of this review is to
      identify similar studies investigating the effects of tocopherol supplementation
      on exercise performance and oxidative stress and to perform minimally biased
      qualitative comparisons and meta-analysis. The literature search and study
      selection were performed according to Cochrane guidelines. A 2-dimensional study
      execution process was developed to enable selection of similar and comparable
      studies. Twenty relevant studies were identified. The high variability of study
      designs resulted in final selection of 6 maximally relevant studies. Markers of
      lipid peroxidation (malondialdehyde) and muscle damage (creatine kinase) were the
      2 most frequently and similarly measured variables. Meta comparison showed that
      tocopherol supplementation did not result in significant protection against
      either exercise-induced lipid peroxidation or muscle damage. The complex
      antioxidant nature of tocopherols and low accumulation rates in muscle tissues
      could underlie an absence of protective effects. 

PMID- 25068791
TI  - Exercise per se masks oral contraceptive-induced postprandial lipid mobilization.
AB  - Because of their hormonal content, oral contraceptives may alter lipolytic
      activity under resting or exercise conditions in women. The aim of the present
      study was to compare lipid mobilization in a postprandial state at rest and
      during exercise in oral contraceptive users (OC+) versus nonusers (OC-). The
      metabolic (glucose, glycerol, free fatty acids) and hormonal (insulin, atrial
      natriuretic peptide (ANP), growth hormone, insulin-like growth factor-1 (IGF-1),
      and catecholamines) concentrations were determined in 11 OC+ (monophasic low-dose
      oral contraceptives) and 10 OC- during a resting and an exercise session (45 min
      at 65% maximal oxygen consumption). Results were expressed as plasma
      concentrations and area under the concentration versus time curve values. ANP
      concentrations were higher in OC+ compared with OC- women at baseline (p = 0.04).
      Plasma concentrations of glycerol (p = 0.04), free fatty acids (p = 0.04), ANP (p
      = 0.02), and noradrenaline (p = 0.04) were higher in OC+ compared with OC- when
      both sessions were pooled. The plasma growth hormone, IGF-1, and adrenaline
      concentrations were not significantly different between the 2 groups. When the
      effect of exercise was isolated to overcome food intake and daytime variations
      (exercise per se using the area under the curve), no difference was observed
      between groups for all metabolic and hormonal variables. Overall, oral
      contraceptives increased lipid mobilization in the postprandial state, but this
      effect was blunted when lipolytic activity was stimulated by exercise per se.
      Oral contraceptive-induced greater lipolytic mobilization could be partly
      explained by greater ANP levels in OC users. 

PMID- 25068787
TI  - The role of cytokines in breast cancer development and progression.
AB  - Cytokines are highly inducible, secretory proteins that mediate intercellular
      communication in the immune system. They are grouped into several protein
      families that are referred to as tumor necrosis factors, interleukins,
      interferons, and colony-stimulating factors. In recent years, it has become clear
      that some of these proteins as well as their receptors are produced in the
      organisms under physiological and pathological conditions. The exact initiation
      process of breast cancer is unknown, although several hypotheses have emerged.
      Inflammation has been proposed as an important player in tumor initiation,
      promotion, angiogenesis, and metastasis, all phenomena in which cytokines are
      prominent players. The data here suggest that cytokines play an important role in
      the regulation of both induction and protection in breast cancer. This knowledge
      could be fundamental for the proposal of new therapeutic approaches to
      particularly breast cancer and other cancer-related disorders. 

PMID- 25068792
TI  - Influence of dietary nitrate on the physiological determinants of exercise
      performance: a critical review.
AB  - Dietary nitrate supplementation, usually in the form of beetroot juice, has been
      heralded as a possible new ergogenic aid for sport and exercise performance.
      Early studies in recreationally active participants indicated that nitrate
      ingestion significantly reduces the O2 cost of submaximal exercise and improves
      performance during high-intensity endurance exercise. Subsequent studies have
      begun to address the physiological mechanisms underpinning these observations and
      to investigate the human populations in whom, and the exercise conditions (high-
      vs. low-intensity, long- vs. short-duration, continuous vs. intermittent,
      normoxic vs. hypoxic) under which, nitrate supplementation may be beneficial.
      Moreover, the optimal nitrate loading regimen in terms of nitrate dose and
      duration of supplementation has been explored. Depending on these factors,
      nitrate supplementation has been shown to exert physiological effects that could
      be conducive to exercise performance enhancement, at least in recreationally
      active or sub-elite athletes. This article provides a "state-of-the-art" review
      of the literature pertinent to the evaluation of the efficacy of nitrate
      supplementation in altering the physiological determinants of sport and exercise
      performance. 

PMID- 25068793
TI  - Development of molecularly imprinted poly(methacrylic acid)/silica for clean-up
      and selective extraction of cholesterol in milk prior to analysis by HPLC-UV.
AB  - In the present paper the assessment of a novel molecularly imprinted polymer,
      poly(methacrylic acid)/silica, for clean-up and selective extraction of
      cholesterol in milk samples is described. The relative selectivity coefficient
      (k) values for cholesterol/5-alpha-cholestane and cholesterol/7
      dehydrocholesterol systems were found to be 5.08 and 6.08, respectively, thus
      attesting the selectivity of the MIP for cholesterol under competitive adsorption
      with structurally analogous steroid compounds. The milk analysis was initially
      based on saponification followed by liquid-liquid extraction with n-hexane. Then,
      the protocol of molecularly imprinted solid phase extraction (MISPE) was carried
      out by loading the milk hexanic extract through 200 mg of MIP or NIP (non
      imprinted polymer) packed into SPE cartridges at a flow rate of 0.6 mL min(-1).
      The washing step was performed by using n-hexane followed by further elution with
      ethanol and HPLC-UV analysis at 208 nm. From the breakthrough curve the maximum
      adsorption capacity of the MIP towards cholesterol was found to be 29.51 mg g(
      1). The precision of the MISPE protocol was assessed as intra- and inter-days
      yielding RSD (relative standard deviations) lower than 4.10%. Cleaner HPLC
      chromatograms were obtained for milk samples submitted to the MISPE protocol in
      comparison to the solid phase extraction using the NIP or modified octadecyl
      silica (C18). Recoveries varying from 96.6 up to 102.2% for milk samples spiked
      with cholesterol were achieved, thus ensuring the accuracy of the proposed
      method. 

PMID- 25068794
TI  - Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3
      in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining
      neuronal death.
AB  - Phthalates, phthalic acid esters, are widely used as plasticizers to produce
      polymeric materials in industrial production of plastics and daily consumable
      products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may
      cause toxic effects in the rat brain. In the present study, chronic exposure to
      DEHP (0.1-100MUM) caused dose-dependent cell death via the activation of caspase
      3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the
      pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC
      inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore,
      DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after
      24 and 48h exposures. However, Sp3 protein reduction was prevented by pre
      treatment with MC-1568, suggesting the involvement of class II HDACs in causing
      this effect. Then, we investigated the possible relationship between DEHP-induced
      neuronal death and the post-translational mechanisms responsible for the down
      regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to
      its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed
      that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4
      inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced
      degradation of Sp3. Notably, Sp3 overexpression was able to counteract the
      detrimental effect induced by DEHP. Taken together, these results suggest that
      DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and
      afterwards, Sp3-polyubiquitination. 

PMID- 25068795
TI  - Combining life cycle assessment and qualitative risk assessment: the case study
      of alumina nanofluid production.
AB  - In this paper the authors propose a framework for combining life cycle assessment
      (LCA) and Risk Assessment (RA) to support the sustainability assessment of
      emerging technologies. This proposal includes four steps of analysis:
      technological system definition; data collection; risk evaluation and impacts
      quantification; results interpretation. This scheme has been applied to a case
      study of nanofluid alumina production in two different pilot lines, "single
      stage" and "two-stage". The study has been developed in the NanoHex project
      (enhanced nano-fluid heat exchange). Goals of the study were analyzing the
      hotspots and highlighting possible trade-off between the results of LCA, which
      identifies the processes having the best environmental performance, and the
      results of RA, which identifies the scenarios having the highest risk for
      workers. Indeed, due to lack of data about exposure limits, exposure-dose
      relationships and toxicity of alumina nanopowders (NPs) and nanofluids (NF), the
      workplace exposure has been evaluated by means of qualitative risk assessment,
      using Stoffenmanager Nano. Though having different aims, LCA and RA have a
      complementary role in the description of impacts of
      products/substances/technologies. Their combined use can overcome limits of each
      of them and allows a wider vision of the problems to better support the decision
      making process. 

PMID- 25068796
TI  - Silencing of hypoxia-inducible factor-1beta induces anti-tumor effects in
      hepatoma cell lines under tumor hypoxia.
AB  - Dimerization of hypoxia-inducible factor-1 beta (HIF-1beta) [aryl hydrocarbon
      receptor nuclear translocator (ARNT)] with HIF-1alpha is involved in various
      aspects of cancer biology, including proliferation and survival under hypoxic
      conditions. We investigated the in vitro mechanism by which silencing of HIF
      1beta leads to the suppression of tumor cell growth and cellular functions.
      Various hepatocellular carcinoma (HCC) cell lines (Huh-7, Hep3B, and HepG2) were
      transfected with small interfering RNA (siRNA) against HIF-1beta (siHIF-1beta)
      and cultured under hypoxic conditions (1% O2 for 24 h). The expression levels of
      HIF-1beta, HIF-1alpha, and growth factors were examined by immunoblotting. Tumor
      growth was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, and tumor activity was measured by terminal
      deoxynucleotidyl transferase dUTP nick end labeling, tumor cell invasion, and
      migration assays. Under hypoxic conditions, silencing of HIF-1beta expression
      suppressed tumor cell growth and regulated the expression of tumor growth-related
      factors, such as vascular endothelial growth factor, epidermal growth factor, and
      hepatocyte growth factor. Suppression of tumor cell invasion and migration was
      also demonstrated in HIF-1beta-silenced HCC cell lines. Silencing of HIF-1beta
      expression may induce anti-tumor effects under hypoxic conditions in HCC cell
      lines. 

PMID- 25068798
TI  - Multifunctional upconverting nanoparticles for near-infrared triggered and
      synergistic antibacterial resistance therapy.
AB  - To integrate photodynamic therapy with photothermal therapy for improved
      multidrug-resistant bacteria therapy, we have constructed a novel multifunctional
      core/satellite nanostructure by decorating CuS nanoparticles onto the surface of
      NaYF4:Mn/Yb/Er@photosensitizer doped SiO2. This system exhibited a superior
      antibacterial activity towards drug-resistant Staphylococcus aureus and
      Escherichia coli. 

PMID- 25068797
TI  - Carbamoylating activity associated with the activation of the antitumor agent
      laromustine inhibits angiogenesis by inducing ASK1-dependent endothelial cell
      death.
AB  - The anticancer agent 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2
      [(methylamino)carbonyl]hydrazine (laromustine), upon decomposition in situ,
      yields methyl isocyanate and the chloroethylating species 1,2-bis(methylsulfonyl)
      1-(2-chloroethyl)hydrazine (90CE). 90CE has been shown to kill tumor cells via a
      proposed mechanism that involves interstrand DNA cross-linking. However, the role
      of methyl isocyanate in the antineoplastic function of laromustine has not been
      delineated. Herein, we show that 1,2-bis(methylsulfonyl)-1
      [(methylamino)carbonyl]hydrazine (101MDCE), an analog of laromustine that
      generates only methyl isocyanate, activates ASK1-JNK/p38 signaling in endothelial
      cells (EC). We have previously shown that ASK1 forms a complex with reduced
      thioredoxin (Trx1) in resting EC, and that the Cys residues in ASK1 and Trx1 are
      critical for their interaction. 101MDCE dissociated ASK1 from Trx1, but not from
      the phosphoserine-binding inhibitor 14-3-3, in whole cells and in cell lysates,
      consistent with the known ability of methyl isocyanate to carbamoylate free thiol
      groups of proteins. 101MDCE had no effect on the kinase activity of purified
      ASK1, JNK, or the catalytic activity of Trx1. However, 101MDCE, but not 90CE,
      significantly decreased the activity of Trx reductase-1 (TrxR1). We conclude that
      methyl isocyanate induces dissociation of ASK1 from Trx1 either directly by
      carbamoylating the critical Cys groups in the ASK1-Trx1 complex or indirectly by
      inhibiting TrxR1. Furthermore, 101MDCE (but not 90CE) induced EC death through a
      non-apoptotic (necroptotic) pathway leading to inhibition of angiogenesis in
      vitro. Our study has identified methyl isocyanates may contribute to the
      anticancer activity in part by interfering with tumor angiogenesis. 

PMID- 25068799
TI  - Remote control of reversible localized protein adsorption in microfluidic
      devices.
AB  - We present a facilely prepared graphene oxide (GO)/ poly(dimethylsiloxane) (PDMS)
      composite by dispersing nanosized GO in PDMS. On the basis of the combination of
      photothermal effects of GO and grafted thermoresponsive polymer, poly(N
      isopropylacrylamide) (PNIPAAm), an optical-driving approach for remote control of
      localized wettability is realized. And this method has been successfully applied
      in the spatially controlled reversible protein adsorption in microfluidic
      devices. 

PMID- 25068802
TI  - Can anaerobic performance be improved by remote ischemic preconditioning?
AB  - Remote ischemic preconditioning (RIPC) provides a substantial benefit for heart
      protection during surgery. Recent literature on RIPC reveals the potential to
      benefit the enhancement of sports performance as well. The aim of this study was
      to investigate the effect of RIPC on anaerobic performance. Seventeen healthy
      participants who practice regular physical activity participated in the project
      (9 women and 8 men, mean age 28 +/- 8 years). The participants were randomly
      assigned to an RIPC intervention (four 5-minute cycles of ischemia reperfusion,
      followed by 5 minutes using a pressure cuff) or a SHAM intervention in a
      crossover design. After the intervention, the participants were tested for
      alactic anaerobic performance (6 seconds of effort) followed by a Wingate test
      (lactic system) on an electromagnetic cycle ergometer. The following parameters
      were evaluated: average power, peak power, the scale of perceived exertion,
      fatigue index (in watt per second), peak power (in Watt), time to reach peak
      power (in seconds), minimum power (in Watt), the average power-to-weight ratio
      (in watt per kilogram), and the maximum power-to-weight ratio (in watt per
      kilogram). The peak power for the Wingate test is 794 W for RIPC and 777 W for
      the control group (p = 0.208). The average power is 529 W (RIPC) vs. 520 W for
      controls (p = 0.079). Perceived effort for RIPC is 9/10 on the Borg scale vs.
      10/10 for the control group (p = 0.123). Remote ischemic preconditioning does not
      offer any significant benefits for anaerobic performance.

PMID- 25068801
TI  - Variation in indigenous forest resource use in central Guyana.
AB  - Sustainable forest conservation strategies should be based on local as well as
      landscape-scale forest resource use data. Using ecological and sociological
      techniques, we test the hypotheses that (1) forest resource use differs between
      ethnic and socioeconomic indigenous groups and (2) that this difference results
      in differing spatial patterns of resource use, with implications for forest
      diversity and for conservation planning. In the North Rupununi Guyana, three
      adjacent indigenous communities (differing in their indigenous/immigrant balance)
      were recorded using 73 animal and 164 plant species (plus several unidentified
      ethno-species). Farm sites formed important foci for most forest based activities
      and ex-farm sites supported similar floristic diversity to surrounding forest.
      Resource usage differences between communities could be attributed to socio
      cultural drivers, e.g. mammal meat consumption and the use of the fruits from the
      palm tree A. maripa were higher in more traditional households. When extracting
      household construction timber, lower income groups created small scattered
      felling sites akin to tree fall gaps whereas higher income groups created larger
      gaps. Lower income (indigenous) households tended to clear larger but more
      contained sites for farming while mixed or non-Amerindian household tended to
      clear smaller but more widely dispersed farm sites. These variations resulted in
      different patterns of forest disturbance originating from agriculture and timber
      extraction. 

PMID- 25068803
TI  - The energy and protein value of wheat, maize and blend DDGS for cattle and
      evaluation of prediction methods.
AB  - The chemical composition inclusive amino acids (AAs) and the energy and protein
      value of three wheat, three maize and seven blend (mainly wheat) dried distillers
      grains and solubles (DDGS) were determined. The net energy for lactation (NEL)
      was derived from digestion coefficients obtained with sheep. The digestible
      protein in the intestines (DVE) and the degraded protein balance (OEB) were
      determined by nylon bag incubations in the rumen and the intestines of cannulated
      cows. Additional chemical parameters like acid-detergent insoluble CP (ADICP),
      protein solubility in water, in borate-phosphate buffer and in pepsin-HCl, in
      vitro digestibility (cellulase, protease, rumen fluid) and colour scores (L*, a*,
      b*) were evaluated as potential predictors of the energy and protein value.
      Compared to wheat DDGS (WDDGS), maize DDGS (MDDGS) had a higher NEL-value (8.49
      v. 7.38 MJ/kg DM), a higher DVE-content (216 v. 198 g/kg DM) and a lower OEB
      value (14 v. 66 g/kg DM). The higher energy value of MDDGS was mainly due to the
      higher crude fat (CFA) content (145 v. 76 g/kg DM) and also to better digestible
      cell-walls, whereas the higher protein value was mainly due to the higher
      percentage of rumen bypass protein (RBP: 69.8 v. 55.6%). The NEL-value of blend
      DDGS (BDDGS) was in between that of the pure DDGS-types, whereas its DVE-value
      was similar to MDDGS. Although lower in CP and total AAs, MDDGS provided a
      similar amount of essential AAs as the other DDGS-types. Lysine content was most
      reduced in the production of WDDGS and cysteine in MDDGS. Fat content explained
      68.6% of the variation in NEL, with hemicellulose and crude ash as extra
      explaining variables. The best predictor for RBP as well as for OEB was the
      protein solubility in pepsin-HCl (R 2=77.3% and 83.5%). Intestinal digestibility
      of RBP could best be predicted by ADF (R 3=73.6%) and the combination of CFA and
      NDF could explain 60.2% of the variation in the content of absorbable microbial
      protein. The availability of AAs could accurately be predicted from the rumen
      bypass and intestinal digestibility of CP. 

PMID- 25068800
TI  - UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor.
AB  - We previously reported a potent small molecule Mer tyrosine kinase inhibitor
      UNC1062. However, its poor PK properties prevented further assessment in vivo. We
      report here the sequential modification of UNC1062 to address DMPK properties and
      yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of
      inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by
      pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse
      bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular
      selectivity assessments demonstrate that 11 has similar subnanomolar activity
      against Flt3, an additional important target in acute myelogenous leukemia (AML),
      with pharmacologically useful selectivity versus other kinases examined. 

PMID- 25068804
TI  - Obituary for professor Garold S. Yost (1948-2014).

PMID- 25068805
TI  - The effect of estrogen on the proliferation of endometrial cancer cells is
      mediated by ERRgamma through AKT and ERK1/2.
AB  - The objective of this study was to explore the effects and underlying mechanism
      of estrogen-related receptor gamma (ERRgamma) on the proliferation of endometrial
      carcinoma cells. Ishikawa cells, human endometrial cancer cells, were treated
      with estrogen. Immunofluorescence was used to observe the expression of ERRgamma.
      Stable transfection with the plasmid containing ERRgamma shRNA was carried out to
      knock down the expression of ERRgamma in Ishikawa cells. MTT assays were
      performed to analyze the proliferation of Ishikawa cells. The activation of
      extracellular signal-regulated protein kinase (ERK)1/2 and activated protein
      kinase B (AKT) signaling pathways was identified using specific phosphorylated
      antibodies against ERK1/2 and AKT. PD98059, a MEK inhibitor, and LY294002, a PI3K
      inhibitor, were used in the inhibition experiments. ERRgamma could translocate
      from the cytoplasm to the nucleus in Ishikawa cells after exposure to estrogen.
      Knockdown of ERRgamma inhibited estrogen-induced proliferation of Ishikawa cells.
      More interestingly, knockdown of ERRgamma abolished the activation of ERK1/2 and
      AKT in the Ishikawa cells treated with estrogen. Inhibition of AKT in Ishikawa
      cells with LY294002 resulted in a significant reduction in the levels of phospho
      ERK1/2, whereas inhibition of ERK1/2 with PD98059 exerted no effects on AKT
      activation. Our data showed that ERRgamma mediated the effects of estrogen on the
      proliferation of endometrial cancer cells through the activation AKT and ERK1/2
      signaling pathways, which indicated that ERRgamma plays a key role in endometrial
      cancer. 

PMID- 25068806
TI  - Twenty nevi on the arms: a simple rule to identify patients younger than 50 years
      of age at higher risk for melanoma.
AB  - Patients with a high total nevus count (TNC) merit a total-body examination, but
      a simple strategy to identify these high-risk individuals is essentially missing.
      The aim of this study was to investigate the correlation between the number of
      melanocytic nevi on both arms and the TNC, and to evaluate patient variables that
      may have an effect on this association. In this multicenter, cross-sectional
      study, 2175 patients were examined and the mean number of arm nevi in relation to
      TNC was calculated. A mean value of fewer than 10 arm nevi was found in patients
      with TNC lower than 51 and a mean value of greater than 19 arm nevi was scored in
      patients with TNC greater than 50. These values remained unchanged after
      adjustment for various patient variables. In relation to TNC greater than 50, the
      presence of 20 or more arm nevi had specificity and negative predictive values of
      95.2 and 89.6%, respectively. The sensitivity was 65.5% in patients younger than
      50 years of age and 37.5% in the older age group. The number of arm nevi was
      significantly higher in individuals with a history of melanoma and in those with
      a melanoma detected during the study period. The presence of 20 or more nevi on
      the arms is an independent predictor of a high TNC and risk of melanoma. This
      sign thus represents a simple and rapid screening tool for either the primary
      care physician or the dermatologist to help identify high-risk patients. 

PMID- 25068807
TI  - Phytoestrogens and breast carcinoma: a word of caution.

PMID- 25068808
TI  - A critique to a review on the relationship between asbestos exposure and the risk
      of mesothelioma.

PMID- 25068809
TI  - A critique of a review on the relationship between asbestos exposure and the risk
      of mesothelioma: reply.

PMID- 25068810
TI  - Generating thermostabilized agonist-bound GPR40/FFAR1 using virus-like particles
      and a label-free binding assay.
AB  - Elucidating the detailed mechanism of activation of membrane protein receptors
      and their ligand binding is essential for structure-based drug design. Membrane
      protein crystal structure analysis successfully aids in understanding these
      fundamental molecular interactions. However, protein crystal structure analysis
      of the G-protein-coupled receptor (GPCR) remains challenging, even for the class
      of GPCRs which have been included in the majority of structure analysis reports
      among membrane proteins, due to the substantial instability of these receptors
      when extracted from lipid bilayer membranes. It is known that increased
      thermostability tends to decrease conformational flexibility, which contributes
      to the generation of diffraction quality crystals. However, this is still not
      straightforward, and significant effort is required to identify thermostabilized
      mutants that are optimal for crystallography. To address this issue, a versatile
      screening platform based on a label-free ligand binding assay combined with
      transient overexpression in virus-like particles was developed. This platform was
      used to generate thermostabilized GPR40 [also known as free fatty acid receptor 1
      (FFAR1)] for fasiglifam (TAK-875). This demonstrated that the thermostabilized
      mutant GPR40 (L42A/F88A/G103A/Y202F) was successfully used for crystal structure
      analysis.

PMID- 25068811
TI  - NMR solution structure of the terminal immunoglobulin-like domain from the
      leptospira host-interacting outer membrane protein, LigB.
AB  - A number of surface proteins specific to pathogenic strains of Leptospira have
      been identified. The Lig protein family has shown promise as a marker in typing
      leptospiral isolates for pathogenesis and as an antigen in vaccines. We used NMR
      spectroscopy to solve the solution structure of the twelfth immunoglobulin-like
      (Ig-like) repeat domain from LigB (LigB-12). The fold is similar to that of other
      bacterial Ig-like domains and comprised mainly of beta-strands that form a beta
      sandwich based on a Greek-key folding arrangement. Based on sequence analysis and
      conservation of structurally important residues, homology models for the other
      LigB Ig-like domains were generated. The set of LigB models illustrates the
      electrostatic differences between the domains as well as the possible
      interactions between neighboring domains. Understanding the structure of the
      extracellular portion of LigB and related proteins is important for developing
      diagnostic methods and new therapeutics directed toward leptospirosis. 

PMID- 25068812
TI  - Emotional labor actors: a latent profile analysis of emotional labor strategies.
AB  - Research on emotional labor focuses on how employees utilize 2 main regulation
      strategies-surface acting (i.e., faking one's felt emotions) and deep acting
      (i.e., attempting to feel required emotions)-to adhere to emotional expectations
      of their jobs. To date, researchers largely have considered how each strategy
      functions to predict outcomes in isolation. However, this variable-centered
      perspective ignores the possibility that there are subpopulations of employees
      who may differ in their combined use of surface and deep acting. To address this
      issue, we conducted 2 studies that examined surface acting and deep acting from a
      person-centered perspective. Using latent profile analysis, we identified 5
      emotional labor profiles-non-actors, low actors, surface actors, deep actors, and
      regulators-and found that these actor profiles were distinguished by several
      emotional labor antecedents (positive affectivity, negative affectivity, display
      rules, customer orientation, and emotion demands-abilities fit) and
      differentially predicted employee outcomes (emotional exhaustion, job
      satisfaction, and felt inauthenticity). Our results reveal new insights into the
      nature of emotion regulation in emotional labor contexts and how different
      employees may characteristically use distinct combinations of emotion regulation
      strategies to manage their emotional expressions at work.

PMID- 25068813
TI  - When teams shift among processes: insights from simulation and optimization.
AB  - This article introduces process shifts to study the temporal interplay among
      transition and action processes espoused in the recurring phase model proposed by
      Marks, Mathieu, and Zacarro (2001). Process shifts are those points in time when
      teams complete a focal process and change to another process. By using team
      communication patterns to measure process shifts, this research explores (a) when
      teams shift among different transition processes and initiate action processes
      and (b) the potential of different interventions, such as communication
      directives, to manipulate process shift timing and order and, ultimately, team
      performance. Virtual experiments are employed to compare data from observed
      laboratory teams not receiving interventions, simulated teams receiving
      interventions, and optimal simulated teams generated using genetic algorithm
      procedures. Our results offer insights about the potential for different
      interventions to affect team performance. Moreover, certain interventions may
      promote discussions about key issues (e.g., tactical strategies) and facilitate
      shifting among transition processes in a manner that emulates optimal simulated
      teams' communication patterns. Thus, we contribute to theory regarding team
      processes in 2 important ways. First, we present process shifts as a way to
      explore the timing of when teams shift from transition to action processes.
      Second, we use virtual experimentation to identify those interventions with the
      greatest potential to affect performance by changing when teams shift among
      processes. Additionally, we employ computational methods including neural
      networks, simulation, and optimization, thereby demonstrating their applicability
      in conducting team research.

PMID- 25068814
TI  - Matrix Gla protein and osteocalcin: from gene duplication to
      neofunctionalization.
AB  - Osteocalcin (OC or bone Gla protein, BGP) and matrix Gla protein (MGP) are two
      members of the growing family of vitamin K-dependent (VKD) proteins. They were
      the first VKD proteins found not to be involved in coagulation and synthesized
      outside the liver. Both proteins were isolated from bone although it is now known
      that only OC is synthesized by bone cells under normal physiological conditions,
      but since both proteins can bind calcium and hydroxyapatite, they can also
      accumulate in bone. Both OC and MGP share similar structural features, both in
      terms of protein domains and gene organization. OC gene is likely to have
      appeared from MGP through a tandem gene duplication that occurred concomitantly
      with the appearance of the bony vertebrates. Despite their relatively close
      relationship and the fact that both can bind calcium and affect mineralization,
      their functions are not redundant and they also have other unrelated functions.
      Interestingly, these two proteins appear to have followed quite different
      evolutionary strategies in order to acquire novel functionalities, with OC
      following a gene duplication strategy while MGP variability was obtained mostly
      by the use of multiple promoters and alternative splicing, leading to proteins
      with additional functional characteristics and alternative gene regulatory
      pathways. 

PMID- 25068815
TI  - Risk prediction score for severe high altitude illness: a cohort study.
AB  - BACKGROUND: Risk prediction of acute mountain sickness, high altitude (HA)
      pulmonary or cerebral edema is currently based on clinical assessment. Our
      objective was to develop a risk prediction score of Severe High Altitude Illness
      (SHAI) combining clinical and physiological factors. Study population was 1017
      sea-level subjects who performed a hypoxia exercise test before a stay at HA. The
      outcome was the occurrence of SHAI during HA exposure. Two scores were built,
      according to the presence (PRE, n = 537) or absence (ABS, n = 480) of previous
      experience at HA, using multivariate logistic regression. Calibration was
      evaluated by Hosmer-Lemeshow chisquare test and discrimination by Area Under ROC
      Curve (AUC) and Net Reclassification Index (NRI). RESULTS: The score was a linear
      combination of history of SHAI, ventilatory and cardiac response to hypoxia at
      exercise, speed of ascent, desaturation during hypoxic exercise, history of
      migraine, geographical location, female sex, age under 46 and regular physical
      activity. In the PRE/ABS groups, the score ranged from 0 to 12/10, a cut-off of
      5/5.5 gave a sensitivity of 87%/87% and a specificity of 82%/73%. Adding
      physiological variables via the hypoxic exercise test improved the discrimination
      ability of the models: AUC increased by 7% to 0.91 (95%CI: 0.87-0.93) and 17% to
      0.89 (95%CI: 0.85-0.91), NRI was 30% and 54% in the PRE and ABS groups
      respectively. A score computed with ten clinical, environmental and physiological
      factors accurately predicted the risk of SHAI in a large cohort of sea-level
      residents visiting HA regions.

PMID- 25068816
TI  - Anisotropic compressive properties of passive porcine muscle tissue.
AB  - The body has approximately 434 muscles, which makes up 40-50% of the body by
      weight. Muscle is hierarchical in nature and organized in progressively larger
      units encased in connective tissue. Like many soft tissues, muscle has nonlinear
      visco-elastic behavior, but muscle also has unique characteristics of
      excitability and contractibility. Mechanical testing of muscle has been done for
      crash models, pressure sore models, back pain, and other disease models. The
      majority of previous biomechanical studies on muscle have been associated with
      tensile properties in the longitudinal direction as this is muscle's primary mode
      of operation under normal physiological conditions. Injury conditions,
      particularly high rate injuries, can expose muscle to multiple stress states.
      Compressive stresses can lead to tissue damage, which may not be reversible. In
      this study, we evaluate the structure-property relationships of porcine muscle
      tissue under compression, in both the transverse and longitudinal orientations at
      0.1 s-1, 0.01 s-1, or 0.001 s-1. Our results show an initial toe region followed
      by an increase in stress for muscle in both the longitudinal and transverse
      directions tested to 50% strain. Strain rate dependency was also observed with
      the higher strain rates showing significantly more stress at 50% strain. Muscle
      in the transverse orientation was significantly stiffer than in the longitudinal
      orientation indicating anisotropy. The mean area of fibers in the longitudinal
      orientation shows an increasing mean fiber area and a decreasing mean fiber area
      in the transverse orientation. Data obtained in this study can help provide
      insight on how muscle injuries are caused, ranging from low energy strains to
      high rate blast events, and can also be used in developing computational injury
      models.

PMID- 25068817
TI  - Overexpression of Oct4 suppresses the metastatic potential of breast cancer cells
      via Rnd1 downregulation.
AB  - Although Oct4 is known as a critical transcription factor involved in maintaining
      "stemness", its role in tumor metastasis is still controversial. Herein, we
      overexpressed and silenced Oct4 expression in two breast cancer cell lines, MDA
      MB-231 and 4T1, separately. Our data showed that ectopic overexpression of Oct4
      suppressed cell migration and invasion in vitro and the formation of metastatic
      lung nodules in vivo. Conversely, Oct4 downregulation increased the metastatic
      potential of breast cancer cells both in vitro and in vivo. Furthermore, we
      identified Rnd1 as the downstream target of Oct4 by ribonucleic acid sequencing
      (RNA-seq) analysis, which was significantly downregulated upon Oct4
      overexpression. Chromatin immunoprecipitation assays revealed the binding of Oct4
      to the promoter region of Rnd1 by ectopic overexpression of Oct4. Dual luciferase
      assays indicated that Oct4 overexpression suppressed transcriptional activity of
      the Rnd1 promoter. Moreover, overexpression of Rnd1 partially rescued the
      inhibitory effects of Oct4 on the migration and invasion of breast cancer cells.
      Overexpression of Rnd1 counteracted the influence of Oct4 on the formation of
      cell adhesion and lamellipodia, which implied a potential underlying mechanism
      involving Rnd1. In addition, we also found that overexpression of Oct4 led to an
      elevation of E-cadherin expression, even in 4T1 cells that possess a relatively
      high basal level of E-cadherin. Rnd1 overexpression impaired the promoting
      effects of Oct4 on E-cadherin expression in MDA-MB-231 cells. These results
      suggest that Oct4 affects the metastatic potential of breast cancer cells through
      Rnd1-mediated effects that influence cell motility and E-cadherin expression. 

PMID- 25068818
TI  - Intimate partner aggression and women's work outcomes.
AB  - Using conservation of resources theory, we examined the relationship between
      intimate partner aggression enacted against heterosexual women and 3 types of
      work-related outcomes for these women: withdrawal while at work (i.e., cognitive
      distraction, work neglect), withdrawal from work (i.e., partial absenteeism,
      intentions to quit), and performance. In Study 1, we compared withdrawal both at
      and from work across 3 clinically categorized groups of women (n = 50), showing
      that experiencing physical aggression is related to higher work neglect. We
      replicated and extended these findings in Study 2 using a community sample of
      employed women (n = 249) by considering the incremental variance explained by
      both physical aggression and psychological aggression on these same outcomes.
      Results showed that physical aggression predicted higher levels of withdrawal
      both at and from work, with psychological aggression predicting additional
      variance in partial absenteeism over and above the effects of physical
      aggression. Study 3 extended the model to include academic performance as an
      outcome in a sample of female college students (n = 122) in dating relationships.
      Controlling for the women's conscientiousness, psychological aggression predicted
      lower academic performance after accounting for the effects of physical
      aggression. We discuss theoretical and practical implications of these results,
      as well as directions for future research.

PMID- 25068819
TI  - Antarctic-wide array of high-resolution ice core records reveals pervasive lead
      pollution began in 1889 and persists today.
AB  - Interior Antarctica is among the most remote places on Earth and was thought to
      be beyond the reach of human impacts when Amundsen and Scott raced to the South
      Pole in 1911. Here we show detailed measurements from an extensive array of 16
      ice cores quantifying substantial toxic heavy metal lead pollution at South Pole
      and throughout Antarctica by 1889 - beating polar explorers by more than 22
      years. Unlike the Arctic where lead pollution peaked in the 1970s, lead pollution
      in Antarctica was as high in the early 20(th) century as at any time since
      industrialization. The similar timing and magnitude of changes in lead deposition
      across Antarctica, as well as the characteristic isotopic signature of Broken
      Hill lead found throughout the continent, suggest that this single emission
      source in southern Australia was responsible for the introduction of lead
      pollution into Antarctica at the end of the 19(th) century and remains a
      significant source today. An estimated 660 t of industrial lead have been
      deposited over Antarctica during the past 130 years as a result of mid-latitude
      industrial emissions, with regional-to-global scale circulation likely modulating
      aerosol concentrations. Despite abatement efforts, significant lead pollution in
      Antarctica persists into the 21(st) century.

PMID- 25068820
TI  - Upcoming drugs for the treatment of preeclampsia in pregnant women.
AB  - Preeclampsia is a pregnancy-specific multisystem disorder, complicating 2 - 8% of
      pregnancies, and represents a leading cause of maternal and perinatal morbidity
      and mortality. Recent investigations have elucidated the understanding of its
      underlying pathogenic mechanisms. However, despite these advances, therapeutic
      approaches are still severely limited. Ongoing lines of research indicate some
      potential novel therapeutic options, targeting the etiopathogenic pathways and,
      thus, offering hope for effective pharmacologic interventions to be available in
      the near future. In this editorial, we will give an updated overview of
      Preeclampsia pathogenesis and promising emerging therapeutic options. 

PMID- 25068821
TI  - Objective analyses of tessellated fundi and significant correlation between
      degree of tessellation and choroidal thickness in healthy eyes.
AB  - A tessellated fundus is a common characteristic of myopic eyes and is an
      important clinical marker for the development of retinochoroidal changes.
      However, the exact cause and significance of tessellated fundi have not been
      definitively determined. We determined the degree of tessellation in fundi
      objectively in normal, non-pathological myopic eyes, and correlated the degree of
      tessellation and the choroidal thickness (CT) and axial length (AL). This was a
      prospective observational cross sectional study. The eyes were classified
      subjectively into three groups based on the degree of tessellation observed
      ophthalmoscopically. Digital color fundus photographs were assessed for the
      degree of tessellation by ImageJ, an image processing program. Three tessellated
      fundus indices (TFIs) were calculated and were compared to the three subjectively
      determined groups. The subfoveal and nasal CTs were measured in the optical
      coherence tomographic images. The correlations between the TFIs and the CT were
      calculated. Additionally, the correlation between the TFIs and the AL was
      calculated. One hundred right eyes of 100 healthy volunteers (mean age 25.8+/-3.9
      years) were studied. Ophthalmoscopically, 57 eyes were placed in the non
      tessellated group, 27 eyes into the weakly tessellated group, and 16 eyes into
      the strongly tessellated group. There was a significant correlation between the
      subjective classifications and the TFI values (P<0.05, Kruskal-Wallis test). All
      of the TFIs were significantly associated with the subfoveal and nasal CT (R = 
      0.20 to -0.24, P<0.05). The TFIs were not significantly correlated with the ALs.
      In conclusion, the significant correlation between the subjective and objective
      classifications of the degree of tessellation indicates that TFIs can be used to
      classify the degree of tessellation. The results indicate that the differences in
      the CT account for the degree of tessellation. 

PMID- 25068822
TI  - A novel biosensor array with a wheel-like pattern for glucose, lactate and
      choline based on electrochemiluminescence imaging.
AB  - Electrochemiluminescence (ECL) imaging provides a superior approach to achieve
      array detection because of its ability for ultrasensitive multiplex analysis. In
      this paper, we reported a novel ECL imaging biosensor array modified with an
      enzyme/carbon nanotubes/chitosan composite film for the determination of glucose,
      choline and lactate. The biosensor array was constructed by integrating a
      patterned indium tin oxide (ITO) glass plate with six perforated
      poly(dimethylsiloxane) (PDMS) covers. ECL is generated by the electrochemical
      reaction between luminol and hydrogen peroxide that is produced by the enzyme
      catalysed oxidation of different substrates with molecular oxygen, and ECL images
      were captured by a charge-coupled device (CCD) camera. The separated
      electrochemical micro-cells enabled simultaneous assay of six samples at
      different concentrations. From the established calibration curves, the detection
      limits were 14 MUM for glucose, 40 MUM for lactate and 97 MUM for choline,
      respectively. Moreover, multicomponent assays and cross reactivity were also
      studied, both of which were satisfied for the analysis. This biosensing platform
      based on ECL imaging shows many distinct advantages, including miniaturization,
      low cost, and multi-functionalization. We believe that this novel ECL imaging
      biosensor platform will have potential applications in clinical diagnostics,
      medicine and food inspection. 

PMID- 25068823
TI  - Devil's Claw to suppress appetite--ghrelin receptor modulation potential of a
      Harpagophytum procumbens root extract.
AB  - Ghrelin is a stomach-derived peptide that has been identified as the only
      circulating hunger hormone that exerts a potent orexigenic effect via activation
      of its receptor, the growth hormone secretagogue receptor (GHS-R1a). Hence, the
      ghrelinergic system represents a promising target to treat obesity and obesity
      related diseases. In this study we analysed the GHS-R1a receptor activating
      potential of Harpagophytum procumbens, popularly known as Devil's Claw, and its
      effect on food intake in vivo. H. procumbens is an important traditional
      medicinal plant from Southern Africa with potent anti-inflammatory and analgesic
      effects. This plant has been also used as an appetite modulator but most
      evidences are anecdotal and to our knowledge, no clear scientific studies
      relating to appetite modulation have been done to this date. The ghrelin receptor
      activation potential of an extract derived from the dried tuberous roots of H.
      procumbens was analysed by calcium mobilization and receptor internalization
      assays in human embryonic kidney cells (Hek) stably expressing the GHS-R1a
      receptor. Food intake was investigated in male C57BL/6 mice following
      intraperitoneal administration of H. procumbens root extract in ad libitum and
      food restricted conditions. Exposure to H. procumbens extract demonstrated a
      significant increased cellular calcium influx but did not induce subsequent GHS
      R1a receptor internalization, which is a characteristic for full receptor
      activation. A significant anorexigenic effect was observed in male C57BL/6 mice
      following peripheral administration of H. procumbens extract. We conclude that H.
      procumbens root extract is a potential novel source for potent anti-obesity
      bioactives. These results reinforce the promising potential of natural bioactives
      to be developed into functional foods with weight-loss and weight maintenance
      benefits. 

PMID- 25068824
TI  - Morin hydrate augments phagocytosis mechanism and inhibits LPS induced autophagic
      signaling in murine macrophage.
AB  - Morin, a natural flavonoid that is the primary bioactive constituent of the
      family Moraceae, has been found to be associated with many therapeutic
      properties. In this study, we evaluated the immunomodulatory activities of
      increasing concentration of morin hydrate in vitro. Three different
      concentrations of morin hydrate (5, 10, and 15MUM) were used to evaluate their
      effect on splenocyte proliferation, phagocytic activity of macrophages, cytokine
      secretion and complement inhibition. We also evaluated the role of morin hydrate
      on lipopolysaccharide (LPS) induced autophagy. Our study demonstrated that morin
      hydrate elicited a significant increase in splenocyte proliferation, phagocytic
      capacity and suppressed the production of cytokines and nitric oxide in activated
      macrophages. Humoral immunity measured by anti-complement activity showed an
      increase in inhibition of the complement system after the addition of morin
      hydrate, where morin hydrate at 15MUM concentration induced a significant
      inhibition. Depending on our results, we can also conclude that morin hydrate
      protects macrophages from LPS induced autophagic cell death. Our findings suggest
      that morin hydrate represents a structurally diverse class of flavonoid and this
      structural variability can profoundly affect its cell-type specificity and its
      biological activities. Supplementation of immune cells with morin hydrate has an
      upregulating and immunoprotective effect that shows potential as a countermeasure
      to the immune dysfunction and suggests an interesting use in inflammation related
      diseases. 

PMID- 25068825
TI  - Usnic acid protects LPS-induced acute lung injury in mice through attenuating
      inflammatory responses and oxidative stress.
AB  - Usnic acid is a dibenzofuran derivative found in several lichen species, which
      has been shown to possess several activities, including antiviral, antibiotic,
      antitumoral, antipyretic, analgesic, antioxidative and anti-inflammatory
      activities. However, there were few reports on the effects of usnic acid on LPS
      induced acute lung injury (ALI). The aim of our study was to explore the effect
      and possible mechanism of usnic acid on LPS-induced lung injury. In the present
      study, we found that pretreatment with usnic acid significantly improved survival
      rate, pulmonary edema. In the meantime, protein content and the number of
      inflammatory cells in bronchoalveolar lavage fluid (BALF) significantly
      decreased, and the levels of MPO, MDA, and H2O2 in lung tissue were markedly
      suppressed after treatment with usnic acid. Meanwhile, the activities of SOD and
      GSH in lung tissue significantly increased after treatment with usnic acid.
      Additionally, to evaluate the anti-inflammatory activity of usnic acid, the
      expression of pro-inflammatory cytokines including tumor necrosis factor alpha
      (TNF-alpha), interleukin-6 (IL-6) and anti-inflammatory cytokine IL-10, and
      chemokines interleukin-8 (IL-8) and macrophage inflammatory protein-2 (MIP-2) in
      BALF were studied. The results in the present study indicated that usnic acid
      attenuated the expression of TNF-alpha, IL-6, IL-8 and MIP-2. Meanwhile, the
      improved level of IL-10 in BALF was observed. In conclusion, these data showed
      that the protective effect of usnic acid on LPS-induced ALI in mice might relate
      to the suppression of excessive inflammatory responses and oxidative stress in
      lung tissue. Thus, it was suggested that usnic acid might be a potential
      therapeutic agent for ALI. 

PMID- 25068826
TI  - The effect of etoricoxib on kidney ischemia-reperfusion injury in rats: a
      biochemical and immunohistochemical assessment.
AB  - The purpose of this study was to investigate the effect of etoricoxib on
      oxidative injury induced with ischemia-reperfusion (I/R) in rat kidney tissue in
      terms of biochemistry and immunohistochemistry. Male Albino Wistar rats were
      divided into renal I/R (RIR), 50 mg/kg etoricoxib+RIR (ETO-50), 100 mg/kg
      etoricoxib+RIR (ETO-100) and sham operation (SG) groups. Animals in the ETO-50
      and ETO-100 groups were given etoricoxib by the oral route at dosages of 50 and
      100 mg/kg, respectively. The RIR and SG groups were given distilled water as
      solvent. One hour after drug administration, 1h of ischemia and 3h of reperfusion
      were applied to the left kidneys of all rats (apart from SG) under 25 mg/kg
      thiopental sodium anesthesia. At the end of that time, kidneys were extracted and
      biochemical and immunohistochemical analyses were performed. Etoricoxib reduced,
      in a dose-dependent manner, levels of MDA, MPO and COX-2 that normally rise with
      I/R in rat kidney tissues. Etorixicob did not alter COX-1 activity at 50 and 100
      mg/kg doses, but significantly prevented loss of tGSH in tissues with I/R. In
      addition, Bcl-2' gene expression inhibited with I/R was prevented in renal
      tubular and glomerular cells. Furthermore, etoricoxib significantly decreased the
      caspase-3 gene expression which increased with I/R. Etoricoxib significantly
      prevented I/R injury in a dose-dependent manner. The results of this study show
      that etoricoxib treatment could decrease kidney injury during IR.

PMID- 25068828
TI  - Association of uteroglobin G38A gene polymorphism with IgA nephropathy risk: an
      updated meta-analysis.
AB  - Association of uteroglobin G38A gene polymorphism and IgA nephropathy (IgAN) risk
      is still not clear. This investigation was conducted to assess if there was an
      association between the uteroglobin G38A gene polymorphism and IgAN risk using
      meta-analysis. The relevant literatures were identified from PubMed, and Cochrane
      Library on 10 October 2013, and eligible studies were included and synthesized.
      Seven reports were recruited into this meta-analysis for the association of the
      uteroglobin G38A gene polymorphism with IgAN risk. In overall population, the A
      allele and AA genotype were not associated with IgAN risk. Furthermore, the GG
      genotype was also not associated with IgAN risk in overall population.
      Interestingly, the association of uteroglobin G38A gene polymorphism with IgAN
      risk was also not found in Asians and in Caucasians. In the sensitivity analysis,
      according to Hardy-Weinberg equilibrium test, according to the control source
      from healthy, the genotyping methods using PCR-RFLP, PCR-SSCP, no association of
      the uteroglobin G38A gene polymorphism with IgAN risk was found and the results
      were similar to those in non-sensitivity analysis. In conclusion, the uteroglobin
      G38A gene polymorphism was not associated with IgAN risk. However, additional
      studies are required to firmly establish a correlation between the uteroglobin
      G38A gene polymorphism and IgAN risk. 

PMID- 25068827
TI  - Urinary concentrations of phthalates in couples planning pregnancy and its
      association with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative stress:
      longitudinal investigation of fertility and the environment study.
AB  - Oxidative stress has been recognized as one of the most important contributors to
      infertility in both males and females. Exposure to many environmental chemicals,
      such as phthalates, has been shown to induce oxidative stress. In a longitudinal
      study designed to assess exposure to environmental chemicals and fecundity in
      couples who were planning pregnancy, 894 urine samples were collected from 469
      couples from Michigan and Texas during 2005-2009. The concentrations of 14
      phthalate metabolites and a marker of oxidative stress, 8-hydroxy-2'
      deoxyguanosine (8-OHdG), were determined in these samples. Concentrations,
      profiles, and estimated daily intakes (DIs) of phthalates were positively
      associated with 8-OHdG. The median concentrations of monomethyl phthalate (mMP),
      monoethyl phthalate (mEP), mono(3-carboxypropyl) phthalate (mCPP), mono-n-butyl
      phthalate (mBP), mono(2-isobutyl) phthalate (miBP), monobenzyl phthalate (mBzP),
      Sigma5mEHP (sum of five metabolites of di(2-ethylhexyl) phthalate (DEHP)) and
      Sigma14phthalates (sum of 14 urinary phthalate metabolites) were 0.48, 85.2,
      4.50, 7.66, 4.36, 3.80, 54.8, and 249 MUg/g creatinine, respectively. The
      estimated DI values for DEHP in 39 individuals were above the U.S. Environmental
      Protection Agency's (EPA) reference dose (RfD) of 20 MUg/kg-bw/day. The mean and
      median concentrations of 8-OHdG were 6.02 and 3.13 MUg/g creatinine,
      respectively, which were significantly higher in females than in males.
      Statistically significant associations were found between 8-OHdG and urinary
      concentrations of mEP, and Sigma5mEHP for females. Similarly, a significant
      association was found between 8-OHdG and DIs estimated for select phthalates. Our
      results suggested that phthalate exposure increases oxidative stress, which can
      be a mechanism for the diminished fertility observed in couples who were highly
      exposed to select phthalates. 

PMID- 25068829
TI  - Diels-Alder cycloadditions on synthetic RNA in mammalian cells.
AB  - Inverse electron demand Diels-Alder cycloadditions are extremely useful tools for
      orthogonal labeling of biomolecules such as proteins or small molecules in a
      cellular context. In-cell labeling of dienophile-modified RNA oligonucleotides
      using Diels-Alder cycloaddition reactions has not been demonstrated before. In
      this study we report site-specific labeling of RNA oligonucleotides modified with
      norbornene derivatives at a predefined sequence position within an RNA sequence
      in vitro and in mammalian cells using various tetrazine-fluorophore conjugates.
      The approach could in future be used as a chemical tool for the detection and
      investigation of RNA functions in cells minimizing the presumed distortion of RNA
      functions by a large chemical reporter group such as a fluorophore. 

PMID- 25068832
TI  - A possible candidate to be classified as an autocatalysis-driven clock reaction:
      kinetics of the pentathionate-iodate reaction.
AB  - The pentathionate-iodate reaction has been investigated by spectrophotometrically
      monitoring the formation of the total amount of iodine at 468 nm in the presence
      of phosphoric acid/dihydrogen phosphate buffer. We noticed that iodine forms only
      after a fairly long time lag, and the inverse of time necessary to produce a
      certain amount of iodine is linearly proportional to the initial concentration of
      iodate ion and the square of the hydrogen ion concentration, while depending
      complexly on the concentration of substrate pentathionate. This reaction can
      therefore be treated as a clock reaction but differs from the original Landolt
      reaction in the sense that substrate pentathionate and the clock species iodine
      coexist for a relatively long time--due to their relatively slow direct reaction-
      depending on the experimental circumstances. Furthermore, we also provided
      experimental evidence that iodide ion acts as an autocatalyst of the system. A 14
      step kinetic model is proposed in which the mechanisms of the pentathionate
      iodine, bisulfite-iodate, and the well-known Dushman reactions are combined. A
      thorough analysis revealed that the direct pentathionate-iodate reaction plays a
      role only to produce iodide ions via a finite sequence of reactions, and once its
      concentration reaches a certain level, the reaction is almost exclusively
      governed by the pentathionate-iodine and the Dushman reactions. As expected, a
      strong catalytic effect of the buffer composition is also found that can readily
      be explained by its well-known catalytic influence on the original Dushman
      reaction.

PMID- 25068830
TI  - Work, diabetes and obesity: a seven year follow-up study among Danish health care
      workers.
AB  - OBJECTIVES: The rise in prevalence of diabetes is alarming and research ascribes
      most of the increase to lifestyle. However, little knowledge exists about the
      influence of occupational factors on the risk for developing diabetes. This study
      estimates the importance of work and lifestyle as risk factors for developing
      diabetes mellitus among healthcare workers and explores the association of work
      factors and obesity, which is a risk factor for diabetes. METHODS: Questionnaire
      based prospective cohort study among 7,305 health care workers followed for seven
      years in the Danish National Diabetes Register. We used bivariate comparisons to
      give an unadjusted estimate of associations, followed by adjusted survival
      analysis and logistic regression models to estimate the influences of potential
      risk factors related to job, health and lifestyle on diabetes and obesity.
      RESULTS: During seven years of follow up, 3.5% of participants developed
      diabetes, associated with obesity (HR  =  6.53; 95% CI 4.68-9.10), overweight (HR
      =  2.89; CI 2.11-3.96) age 50-69 y (HR  =  2.27; 95% CI 1.57-3.43) and high
      quality of leadership (HR  =  1.60; CI 1.19-2.16). Obesity at baseline was most
      common among the youngest employees, and was mainly associated with developing
      diabetes (OR  =  3.84; CI 2.85-5.17), impaired physical capacity and physical
      inactivity. In the occupational setting, obesity was associated with shift work,
      severe musculoskeletal pain, low influence, but also by good management, fewer
      role conflicts and a positive work-life balance. Looking only at non-smokers,
      removed the influence of age and pain. However, non-smokers also had higher
      depression scores and more role conflicts. CONCLUSIONS: Confirming obesity as the
      strongest risk factor for developing diabetes, the present study identified few
      occupational risk factors. However, obesity, the key risk factor for diabetes,
      had a more variable relation with work than did diabetes.

PMID- 25068833
TI  - A rare but serious manifestation of Behcet's disease: intracardiac thrombus in 22
      patients.
AB  - OBJECTIVES: Behcet's disease (BD) is a chronic, multisystemic disorder
      characterised by recurrent oral aphtous ulcers, genital ulcers and ocular
      inflammation. Vasculitis and thrombotic events are the most important causes of
      mortality. Vena cava thrombosis, pulmonary artery aneurysms, Budd-Chiari
      syndrome, peripheral artery aneurysms, dural sinus thrombosis and abdominal aorta
      aneurysms are the other less common vascular manifestations of BD. Cardiac
      involvement in BD is a rare and life-threatening complication. The aim of this
      study was to assess the clinical characteristics and outcome of patients with BD
      who have intracardiac thrombus. METHODS: The hospital files of BD patients
      followed by rheumatology clinics of four medical centres (Ankara University, Ege
      University, Hacettepe University and Eskisehir Osmangazi University Hospitals)
      were retrospectively evaluated. Data included patients' demographic and clinical
      features, laboratory findings and outcome. All patients fulfilled three or more
      of the International Study Group Criteria for BD. RESULTS: Twenty-two patients
      with intracardiac thrombus were evaluated. The mean age of patients with
      intracardiac thrombosis was 29.1 yrs (22-44) and there was a male predominance
      with a ratio of 20:2. Cardiac involvement was the first clinical manifestation of
      BD in 9 of the 22 patients. Initial symptoms of the patients were fever (n=18,
      81%), dyspnea (n=9, 40%) chest pain (n=9, 40%) and haemoptysis (n=7, 31.8%).
      Sixteen patients (72%) had pulmonary arteritis and 10 (45%) patients had venous
      system lesions included deep vein, inferior vena cava and hepatic vein. Intra
      cardiac thrombus were found only in the right cavities in 17 patients (77%), only
      in the left cavities in 2 patients (9%), and in both left and right cavities of
      the heart in 3 patients (13.6%). Once the cardiac lesion was diagnosed as a
      complication of BD, high dose (1mg/kg/d) prednisone (n=22, 100%) plus
      cyclophosphamide (n=18, 81%) or azathioprine (n=3, 13.6%) and warfarin (n=8,
      36.3% (after the elimination of pulmonary aneurysm) therapy for anticoagulation
      was initiated. Four patients (18%) had high dose prednisone plus cyclophosphamide
      plus interferon-alpha (IFN-alpha) combination treatment and two patients (n=2,
      9%) had high dose prednisone plus cyclophosphamide or plus azathioprine
      combination treatment. After treatment, the intra-cardiac thrombus disappeared in
      13 cases and the size of the thrombus reduced in 7 cases. One patient died
      because of recurrent intra-cardiac thrombus and massive pulmonary arteritis in
      the emergency department. CONCLUSIONS: Intracardiac thrombus in BD is more common
      in young men. The right side of the heart is usually involved and cardiac
      involvement is often accompanied by pulmonary artery occlusion possibly due to
      pulmonary arteritis. Early and aggressive immunosuppressive and/or
      anticoagulation therapy are life-saving.

PMID- 25068834
TI  - Brachial artery characteristics and micro-vascular filtration capacity in rock
      climbers.
AB  - Rock climbers perform repeated isometric forearm muscle contractions subjecting
      the vasculature to repeated ischaemia and distorted haemodynamic signals. This
      study investigated forearm vascular characteristics in rock climbers compared to
      healthy untrained controls. Eight climbers (CLIMB) (BMI; 22.3, s = 2.0 kg/m(2),
      isometric handgrip strength; 46, s = 8 kg) were compared against eight untrained
      controls (CON) (BMI; 23.8, s = 2.6 kg/m(2), isometric handgrip strength; 37, s =
      9 kg). Brachial artery diameter and blood flow were measured, using Doppler
      ultrasound, at rest and following 5-mins ischaemia (peak diameter) and ischaemic
      exercise (maximal dilation) to calculate flow mediated dilation (FMD) and
      dilatory capacity (DC). Capillary filtration capacity was assessed using venous
      occlusion plethysmography. Resting (4.30, s = 0.26 vs. 3.79, s = 0.39 mm), peak
      (4.67, s = 0.31 vs. 4.12, s = 0.45 mm) and maximal (5.14, s = 0.42 vs. 4.35, s =
      0.47 mm) diameters were greater (P < 0.05) in CLIMB than CON, respectively,
      despite no difference in FMD (9.2, s = 2.6 vs. 8.7, s = 2.9%). Peak reactive
      hyperaemic blood flow (1136, s = 504 vs. 651, s = 221 ml/min) and capillary
      filtration capacity (3.8, s = 0.9 vs. 5.2, s = 0.7 ml.min(-1).mmHg(-1).100 ml
      tissue(-1) * 10(-3)) were greater (P < 0.05) in CLIMB compared to CON,
      respectively. Rock climbers exhibit structural vascular adaptation compared to
      untrained control participants but have similar vascular function. This may
      contribute to the enhanced ability of climbers to perform repeated isometric
      contractions. 

PMID- 25068835
TI  - Porous, single crystalline titanium nitride nanoplates grown on carbon fibers:
      excellent counter electrodes for low-cost, high performance, fiber-shaped dye
      sensitized solar cells.
AB  - An excellent, platinum free fiber counter electrode (CE) was successfully
      fabricated, consisting of porous, single crystalline titanium nitride (TiN)
      nanoplates grown on carbon fibers (CF). The fiber-shaped dye-sensitized solar
      cells (FDSSCs) based on the TiN-CF CE show a high conversion efficiency of 7.20%,
      comparable or even superior to that of the Pt wire (6.23%). 

PMID- 25068836
TI  - The syllabic status of final consonants in early speech: a case study.
AB  - Young children's first attempts at CVC words are often realized with the final
      consonant being heavily aspirated or followed by an epenthetic vowel (e.g. cat
      /kaet/ realized as [kaeth] or [kaete]). This has led some to propose that young
      children represent word-final (coda) consonants as an onset-nucleus sequence
      (CV.Cv) (e.g. Goad & Brannen, 2003), raising questions about the syllabic status
      of the final consonant. To address this issue, we conducted an acoustic analysis
      of a child's early production of CVC, CVCh, and CVCV words between the ages of
      1;3 and 1;5. Aside from aspiration, the results showed that there were no
      significant acoustic differences between the CVC and CVCh forms. In contrast,
      there were systematic acoustic differences in C2 closure duration between the
      CVC/CVCh and CVCV target words, suggesting that at least some children learning
      English have early coda representations for monosyllabic CVC words, whether
      heavily aspirated or not. 

PMID- 25068838
TI  - Spectroscopic analysis of vermicompost for determination of nutritional quality.
AB  - Spectroscopic analysis has been carried out to examine the compost quality,
      maturity and nutritional levels of vermicompost and compost of Eichhornia. 50%
      Eichhorniacrassipes and 50% cow dung mixtures were vermicomposted using
      earthworms (Eudrilus eugeniae) and collected on different days' time intervals.
      Fourier transform infrared spectroscopy (FT-IR) spectra reveal the presence of
      humic substance from compost and vermicompost, which improves the soil fertility.
      Gas chromatography-mass spectroscopy (GC-MS) analysis shows maximum level of
      Benzene propanoic acid (95.98%) and by 2-Propanone, 1-Phenyl-, OXIM (10.10%) from
      vermicompost through earthworms activity. Atomic absorption spectroscopy (AAS)
      results reported high level of micronutrient from Eichhornia mediated compost and
      vermicompost. 

PMID- 25068837
TI  - Combustion synthesized tetragonal ZrO2: Eu(3+) nanophosphors: structural and
      photoluminescence studies.
AB  - Novel crystalline tetragonal ZrO2: Eu(3+) phosphors were prepared by a facile and
      efficient low temperature solution combustion method at 400+/-10  degrees C using
      oxalyl dihydrazide (ODH) as fuel. The powder X-ray diffraction patterns and
      Rietveld confinement of as formed ZrO2: Eu(3+) (1-11 mol%) confirmed the presence
      of body centered tetragonal phase. The crystallite size estimated from Scherrer's
      and W-H plots was found to be in the range of 7-17 nm. These results were in good
      agreement with transmission electron microscopy studies. The calculated
      microstrain in most of the planes indicated the presence of tensile stress along
      various planes of the particles. The observed space group (P42/nmc) revealed the
      presence of cations in the 2b positions (0.75, 0.25, 0.25) and the anions in the
      4d positions (0.25, 0.25, 0.45). The optical band gap energies estimated from
      Wood and Tauc's relation was found to be in the range 4.3-4.7 eV.
      Photoluminescence (PL) emission was recorded under 394 and 464 nm excitation
      shows an intense emission peak at 605 nm along with other emission peaks at 537,
      592, 605 and 713 nm. These emission peaks were attributed to the transition of
      (5)D0->(7)FJ (J=0, 1, 2, 3) of Eu(3+) ions. The high ratio of Intensity of ((5)D0
      >(7)F2) and ((5)D0->(7)F1) infers that Eu(3+) occupies sites with a low symmetry
      and without an inversion center. CIE color coordinates indicated the red regions
      which could meet the needs of illumination devices.

PMID- 25068839
TI  - Rhodium(III)-catalyzed directed peri-C-H alkenylation of anthracene derivatives.
AB  - Rhodium(III)-catalyzed oxidative coupling reactions of anthracene-9-carboxylic
      acid derivatives with electron-deficient olefins are reported. A cationic
      rhodium(III) catalyst, in combination with a copper(II) oxidant, promotes
      selective monoalkenylation of anthracene-9-carboxamide, affording 1
      alkenylanthracene-9-carboxamide in moderate to good yields. A similar catalytic
      system also promotes the reaction of anthracene-9-carboxylic acid and an electron
      deficient olefin, which affords a lactone derivative through C-H alkenylation
      followed by intramolecular conjugate addition. 

PMID- 25068840
TI  - An organic spin crossover material in water from a covalently linked radical
      dyad.
AB  - A covalently linked viologen radical cation dyad acts as a reversible
      thermomagnetic switch in water. Cycling between diamagnetic and paramagnetic
      forms by heating and cooling is accompanied by changes in optical and magnetic
      properties with high radical fidelity. Thermomagnetic switches in water may
      eventually find use as novel biological thermometers and in temperature
      responsive organic materials where the changes in properties originate from a
      change in electronic spin configuration rather than a change in structure. 

PMID- 25068841
TI  - Proteomic profiling of the acid stress response in Lactobacillus plantarum 423.
AB  - Acid tolerance is considered an important characteristic of probiotic bacteria.
      Lactobacillus plantarum 423 tolerates acidic pH and is the ideal candidate in
      which to study molecular mechanisms that acid-tolerant lactic acid bacteria
      employ to survive such conditions. In this study we recorded changes in the
      protein profile of L. plantarum 423 when exposed to pH 2.5 by using a gel-free
      nanoLC-MS/MS proteomics approach. In total, 97 proteins were detected as more
      abundant, and 12 proteins were detected solely when strain 423 was exposed to pH
      2.5. General stress response proteins, the utilization of a variety of
      carbohydrate sources in a glucose rich environment, altered pyruvate metabolism,
      increased lysine biosynthesis, and a significant oxidative stress response was
      observed in acid-stressed cells. The accumulation of basic compounds also seemed
      to play an integral role in the response to acid stress. We observed a marked
      decrease in proteins involved in cell wall and phospholipid biosynthesis,
      transcription, translation, and cell division. The most abundant protein detected
      was an uncharacterized protein, JDM1_2142. Functional analysis revealed that this
      protein plays a role in survival during acid stress. Our results contribute to
      the growing body of knowledge on the molecular mechanisms employed by
      lactobacilli, in particular L. plantarum, to ensure survival in acidic
      conditions. 

PMID- 25068842
TI  - Incidence and predictive factors for malignancies with dermatomyositis: a cohort
      from southern China.
AB  - OBJECTIVES: We aimed to explore the incidence of malignancy in dermatomyositis
      and assess the potential risk factors of occurrence of malignancy in DM from
      southern China. METHODS: A retrospective cohort study of patients admitted in the
      1st affiliated university hospital between 2003 and 2012 was performed.
      Demographic information, clinical symptoms, laboratory findings, medications were
      documented. The endpoint of the study was defined as occurrence of malignancy or
      death. RESULTS: For this approximately 10-year retrospective study, 60 out of 246
      dermatomyositis patients developed malignancies with the overall incidence of
      24.4%. Nasopharyngeal carcinoma (NPC) and ovarian carcinoma were the most common
      malignant disease, accounting for 35% (21/60) and 15% (9/60) of malignancies,
      respectively. Lung and colon were followed as the third most common carcinoma (5
      out of 60, 8.3%). Among these 60 patients with malignancies, 39 (65.0%, 39/60)
      cases occurred within 1 year after DM diagnosis. Subsequently, malignancies were
      detected in 13 (21.7%, 13/60) patients during the second year and 8 (13.3%, 8/60)
      during the third year. One patient developed cancer at the 35th month after DM as
      the latest. The logistic regression multivariate analysis indicated that male
      gender [odds ratio (OR) = 3.76, 95% confidence interval (CI ) 1.86~7.61, p<0.01],
      dysphagia (OR= 2.21, 95%CI 1.10~4.48, p=0.03) and elevated erythrocyte
      sedimentation rate (ESR) (OR= 2.37, 95% CI 1.18~4.75, p=0.02) were risk factors
      for the occurrence of malignancies, while interstitial lung disease (ILD) acted
      as a protective factor (OR=0.13, 95%CI 0.06~0.28, p<0.01). CONCLUSIONS: It was
      necessary to carry out routine malignancy screening for Chinese DM patients due
      to its high incidence. Nasopharyngeal carcinoma and ovarian cancer were the most
      common malignant disease. The risk of malignancy was highest in the first year
      after DM diagnosis and reduced thereafter. Extensive work-ups for malignancy
      screening should be carried out at the first year. Male gender, dysphagia and
      elevated ESR were risk factors for occurrence of malignancy. The presence of ILD
      could diminish the risk of coexisting of malignancy.

PMID- 25068844
TI  - Staged Bilateral Total Knee Arthroplasty: Time of the Second Side.
AB  - The purpose of this study was to determine if there was a safe time frame for
      performing the second total knee arthroplasty (TKA) in staged bilateral TKAs.
      Retrospectively, 589 TKAs were studied at a single institution from January 2000
      to June 2012. Patients were excluded if they underwent simultaneous or staggered
      bilateral TKA during the same hospitalization. Patients were included if they
      underwent bilateral staged TKA during a different hospitalization within 21 to
      90, 91 to 180, 181 to 270, and 271 to 360 days after the first TKA. In-hospital
      complications were determined using International Classification of Diseases,
      Ninth Revision codes for cardiac, pulmonary, urinary, deep vein thrombosis, wound
      complications, mechanical complications, and wound infections. Periprosthetic
      joint infection (PJI) was determined by hospital readmission records. There were
      29 postoperative complication events (4.9%) and there was no difference between
      time groups and complications. The highest rates of PJI occurred when the second
      TKA was performed after 271 to 360 days (3.6%), followed by the early
      postoperative period after 21 to 90 days (2.7%). We could not identify a time
      frame for performing the second TKA in staged bilateral TKAs to reduce
      complications. A signal from the study suggests that complications, particularly
      PJI, may be lower if the second TKA is performed more than 90 days and less than
      270 days after the first TKA, although this finding was not significant. 

PMID- 25068843
TI  - X-ray absorption spectroscopy systematics at the tungsten L-edge.
AB  - A series of mononuclear six-coordinate tungsten compounds spanning formal
      oxidation states from 0 to +VI, largely in a ligand environment of inert chloride
      and/or phosphine, was interrogated by tungsten L-edge X-ray absorption
      spectroscopy. The L-edge spectra of this compound set, comprised of
      [W(0)(PMe3)6], [W(II)Cl2(PMePh2)4], [W(III)Cl2(dppe)2][PF6] (dppe = 1,2
      bis(diphenylphosphino)ethane), [W(IV)Cl4(PMePh2)2], [W(V)(NPh)Cl3(PMe3)2], and
      [W(VI)Cl6], correlate with formal oxidation state and have usefulness as
      references for the interpretation of the L-edge spectra of tungsten compounds
      with redox-active ligands and ambiguous electronic structure descriptions. The
      utility of these spectra arises from the combined correlation of the estimated
      branching ratio of the L3,2-edges and the L1 rising-edge energy with metal Zeff,
      thereby permitting an assessment of effective metal oxidation state. An
      application of these reference spectra is illustrated by their use as backdrop
      for the L-edge X-ray absorption spectra of [W(IV)(mdt)2(CO)2] and
      [W(IV)(mdt)2(CN)2](2-) (mdt(2-) = 1,2-dimethylethene-1,2-dithiolate), which shows
      that both compounds are effectively W(IV) species even though the mdt ligands
      exist at different redox levels in the two compounds. Use of metal L-edge XAS to
      assess a compound of uncertain formulation requires: (1) Placement of that data
      within the context of spectra offered by unambiguous calibrant compounds,
      preferably with the same coordination number and similar metal ligand distances.
      Such spectra assist in defining upper and/or lower limits for metal Zeff in the
      species of interest. (2) Evaluation of that data in conjunction with information
      from other physical methods, especially ligand K-edge XAS. (3) Increased care in
      interpretation if strong pi-acceptor ligands, particularly CO, or pi-donor
      ligands are present. The electron-withdrawing/donating nature of these ligand
      types, combined with relatively short metal-ligand distances, exaggerate the
      difference between formal oxidation state and metal Zeff or, as in the case of
      [W(IV)(mdt)2(CO)2], exert the subtle effect of modulating the redox level of
      other ligands in the coordination sphere. 

PMID- 25068845
TI  - How do spanning external fixators on knee dislocation patients affect the use of
      MRI and knee stability?
AB  - This study sought to determine the following: (1) Does the external fixator
      compromise quality of imaging obtained? (2) How do findings from the evaluation
      under anesthesia at the time of external fixator removal compare with the initial
      magnetic resonance imaging (MRI) findings? This was a retrospective study of a
      consecutive patient series at an academic level 1 trauma center. There were 19
      consecutive patients with traumatic knee dislocations and spanning external
      fixator applied. Each patient had a knee MRI with the external fixator in place
      and examination at the time of external fixator removal. A review of knee
      stability at the time of external fixator removal with physical examination and
      stress fluoroscopy were performed. Our study revealed only minor incidence of
      poorly visualized structures. Clinical stability was present after fixator
      removal in only 11 of 14 medial collateral ligament tears, 4 of 16 lateral
      collateral ligament tears, 1 of 19 anterior cruciate ligament tears and 3 of 19
      posterior cruciate ligament tears. MRI is a useful imaging modality in the
      setting of knee dislocations placed in spanning external fixators. Patients'
      knees largely remain unstable after external fixator removal. 

PMID- 25068846
TI  - Current strategies and approaches to meniscal repair.
AB  - Repair of symptomatic meniscal tears in the appropriate patient has demonstrated
      successful mid and long-term results with a variety of different repair
      techniques. These techniques have undergone much evolution and innovation, from
      the initial open repairs to a variety of inside-out, outside-in, and all-inside
      techniques and devices. This article focuses on patient presentation, selection,
      current treatments, and surgical techniques including pearls and pitfalls, and
      discusses the most recent published outcomes and complications. 

PMID- 25068847
TI  - Role of platelet-rich plasma in articular cartilage injury and disease.
AB  - Clinical and laboratory research aimed at biological approaches to cartilage
      repair are currently in high demand due to the poor regenerative capacity of
      articular cartilage in the setting of a diseased articular environment. Platelet
      rich plasma (PRP) takes advantage of supraphysiological concentrations of
      platelets and their growth factors harbored in alpha-granules, which together
      attempt to return the diseased articular cartilage to a preinjury state. The
      local use of PRP directly at the site of cartilage injury is thought to stimulate
      a natural healing cascade and accelerate the formation of cartilage repair
      tissue. This article provides an overview of the basic science behind the use of
      PRP in the treatment of cartilage injury and disease. Both initial and current
      examples of the use of intra-articular PRP in clinical human studies are
      provided. These include the use of PRP either alone or as an augmentation device
      with various other procedures, including arthroscopic microfracture and cell-free
      resorbable polyglycolic acid-hyaluronan implantation. Finally, the authors
      describe some of the potential future roles of PRP in clinical settings based on
      recent literature. These include Achilles tendon rupture, chronic tendinosis,
      chronic rotator cuff tendinopathy or tearing, muscle injury, and meniscal repair.

PMID- 25068848
TI  - Qualitative evidence on abortion stigma from Mexico City and five states in
      Mexico.
AB  - Social manifestations of abortion stigma depend upon cultural, legal, and
      religious context. Abortion stigma in Mexico is under-researched. This study
      explored the sources, experiences, and consequences of stigma from the
      perspectives of women who had had an abortion, male partners, and members of the
      general population in different regional and legal contexts. We explored abortion
      stigma in Mexico City where abortion is legal in the first trimester and five
      states-Chihuahua, Chiapas, Jalisco, Oaxaca, and Yucatan-where abortion remains
      restricted. In each state, we conducted three focus groups-men ages 24-40 years
      (n = 36), women 25-40 years (n = 37), and young women ages 18-24 years (n = 27)
      and four in-depth face-to-face interviews in total; two with women (n = 12) and
      two with the male partners of women who had had an abortion (n = 12). For 4 of
      the 12 women, this was their second abortion. This exploratory study suggests
      that abortion stigma was influenced by norms that placed a high value on
      motherhood and a conservative Catholic discourse. Some participants in this study
      described abortion as an "indelible mark" on a woman's identity and "divine
      punishment" as a consequence. Perspectives encountered in Mexico City often
      differed from the conservative postures in the states.

PMID- 25068849
TI  - Human monocytes in the presence of interferons alpha2a and gamma are potent
      killers of serous ovarian cancer cell lines in combination with paclitaxel and
      carboplatin.
AB  - Interferons (IFNs) play an important role in immune surveillance of tumors;
      however, their efficacy in the treatment of malignancies has been limited.
      Monocytes are mononuclear phagocytes that are critical to the generation of an
      innate immune response to tumors. The authors and others have shown that
      treatment of tumor cell lines in vitro and in vivo with human monocytes primed
      with type I and type II IFNs results in killing. We now expand on this work, in
      an extended panel of ovarian cancer cell lines. In this study, we hypothesized
      that there would be variable sensitivity amongst cell lines to the killing
      properties of monocytes and IFNs. To this end, we explored the interactions of
      IFN primed monocytes in conjunction with the standard of therapy for ovarian
      cancer, taxane, and platinum-based chemotherapeutics. Using 6 ovarian cancer cell
      lines, we demonstrated that there is variation from cell line to cell line in the
      ability of IFN-alpha2a and IFN-gamma primed monocytes to synergistically kill
      target tumor cells, and further, there is an additive killing effect when target
      cells are treated with both IFN primed monocytes and chemotherapy. 

PMID- 25068851
TI  - Components of attention modulated by temporal expectation.
AB  - By varying the probabilities that a stimulus would appear at particular times
      after the presentation of a cue and modeling the data by the theory of visual
      attention (Bundesen, 1990), Vangkilde, Coull, and Bundesen (2012) provided
      evidence that the speed of encoding a singly presented stimulus letter into
      visual short-term memory (VSTM) is modulated by the observer's temporal
      expectations. We extended the investigation from single-stimulus recognition to
      whole report (Experiment 1) and partial report (Experiment 2). Cue-stimulus
      foreperiods were distributed geometrically using time steps of 500 ms. In high
      expectancy conditions, the probability that the stimulus would appear on the next
      time step, given that it had not yet appeared, was high, whereas in low
      expectancy conditions, the probability was low. The speed of encoding the stimuli
      into VSTM was higher in the high expectancy conditions. In line with the
      Easterbrook (1959) hypothesis, under high temporal expectancy, the processing was
      also more focused (selective). First, the storage capacity of VSTM was lower, so
      that fewer stimuli were encoded into VSTM. Second, the distribution of
      attentional weights across stimuli was less even: The efficiency of selecting
      targets rather than distractors for encoding into VSTM was higher, as was the
      spread of the attentional weights of the target letters.

PMID- 25068850
TI  - Inter individual variations of the fish skin microbiota: host genetics basis of
      mutualism?
AB  - The commensal microbiota of fish skin is suspected to provide a protection
      against opportunist infections. The skin of fish harbors a complex and diverse
      microbiota that closely interacts with the surrounding water microbial
      communities. Up to now there is no clear evidence as to whether the host
      regulates the recruitment of environmental bacteria to build a specific skin
      microbiota. To address this question, we detected Quantitative Trait Loci (QTL)
      associated with the abundance of specific skin microbiota bacterial strains in
      brook charr (Salvelinus fontinalis), combining 16S RNA tagged-amplicon 454
      pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed
      high inter-individual variation among 86 F2 fish progeny based upon the relative
      abundance of bacterial operational taxonomic units (OTUs). Out of those OTUs, the
      pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain
      Methylobacterium rhodesianum explained the majority of inter-individual
      distances. Furthermore, a strong negative correlation was found between
      Flavobacterium and Methylobacterium, suggesting a mutually competitive
      relationship. Finally, after considering a total of 266 markers, genetic linkage
      analysis highlighted three major QTL associated with the abundance of Lysobacter,
      Rheinheimera and Methylobacterium. All these three genera are known for their
      beneficial antibacterial activity. Overall, our results provide evidence that
      host genotype may regulate the abundance of specific genera among their surface
      microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium
      are potentially important genera in providing protection against pathogens. 

PMID- 25068852
TI  - Effects of order of mention and grammatical role on anaphor resolution.
AB  - A controversial issue in anaphoric processing has been whether processing
      preferences of anaphoric expressions are affected by the antecedent's grammatical
      role or surface position. Using eye tracking, Experiment 1 examined the
      comprehension of pronouns during reading, which revealed shorter reading times in
      the pronoun region and later regions when the antecedent was the subject than
      when it was the prepositional object. There was no effect of antecedent position.
      Experiment 2 showed that the choice between pronouns and repeated names during
      language production is also primarily affected by the antecedent's grammatical
      role. Experiment 3 examined the comprehension of repeated names, showing a clear
      effect of antecedent position. Reading times in the name region and in later
      regions were longer when the antecedent was 1st mentioned than 2nd mentioned,
      whereas the antecedent's grammatical role only affected regression measures in
      the name region, showing more processing difficulty with a subject than
      prepositional-object antecedent. Thus, the processing of pronouns is primarily
      driven by antecedent grammatical role rather than position, whereas the
      processing of repeated names is most strongly affected by position, suggesting
      that different representations and processing constraints underlie the processing
      of pronouns and names.

PMID- 25068853
TI  - Toward a model framework of generalized parallel componential processing of multi
      symbol numbers.
AB  - In this article, we propose and evaluate a new model framework of parallel
      componential multi-symbol number processing, generalizing the idea of parallel
      componential processing of multi-digit numbers to the case of negative numbers by
      considering the polarity signs similar to single digits. In a first step, we
      evaluated this account by defining and investigating a sign-decade compatibility
      effect for the comparison of positive and negative numbers, which extends the
      unit-decade compatibility effect in 2-digit number processing. Then, we evaluated
      whether the model is capable of accounting for previous findings in negative
      number processing. In a magnitude comparison task, in which participants had to
      single out the larger of 2 integers, we observed a reliable sign-decade
      compatibility effect with prolonged reaction times for incompatible (e.g., -97
      vs. +53; in which the number with the larger decade digit has the smaller, i.e.,
      negative polarity sign) as compared with sign-decade compatible number pairs
      (e.g., -53 vs. +97). Moreover, an analysis of participants' eye fixation behavior
      corroborated our model of parallel componential processing of multi-symbol
      numbers. These results are discussed in light of concurrent theoretical notions
      about negative number processing. On the basis of the present results, we propose
      a generalized integrated model framework of parallel componential multi-symbol
      processing.

PMID- 25068854
TI  - The representation of concrete and abstract concepts: categorical versus
      associative relationships.
AB  - In 4 word-translation experiments, we examined the different representational
      frameworks theory (Crutch & Warrington, 2005; 2010) that concrete words are
      represented primarily by category, whereas abstract words are represented by
      association. In our experiments, Chinese-English bilingual speakers were
      presented with an auditory Chinese word and 3 or 4 written English words
      simultaneously and asked to select the English word that corresponded to the
      auditory word. For both abstract and concrete words, higher error rates and
      longer response times were observed when the English words were categorically or
      associatively related compared to the unrelated conditions and the magnitude of
      the categorical effect was bigger than the associative effect. These results
      challenge the different representational frameworks theory and suggest that
      although category and association are important for representing abstract and
      concrete concepts, category plays a greater role for both types of words.

PMID- 25068856
TI  - Parafoveal lexical activation depends on skilled reading proficiency.
AB  - The boundary paradigm was used to investigate individual differences in the
      extraction of lexical information from the parafovea in sentence reading. The
      preview of a target word was manipulated so that it was identical (e.g., sped), a
      higher frequency orthographic neighbor (seed), a nonword neighbor (sted), or an
      all-letter-different nonword (glat). Ninety-four skilled adult readers were
      assessed on measures of reading and spelling ability. The results showed that
      null effects of preview lexical status in the average data obscured systematic
      differences on the basis of proficiency and target neighborhood density. For
      targets from dense neighborhoods, inhibition from a higher frequency neighbor
      preview occurred among highly proficient readers, and particularly those with
      superior spelling ability, in early fixation measures. Poorer readers showed
      inhibition only in second-pass reading of the target. These data suggest that
      readers with precise lexical representations are more likely to extract lexical
      information from a word before it is fixated. The implications for computational
      models of eye movements in reading are discussed.

PMID- 25068855
TI  - Why two heads apart are better than two heads together: multiple mechanisms
      underlie the collaborative inhibition effect in memory.
AB  - Although a group of people working together remembers more than any one
      individual, they recall less than their predicted potential. This finding is
      known as collaborative inhibition and is generally thought to arise due to
      retrieval disruption. However, there is growing evidence that is inconsistent
      with the retrieval disruption account, suggesting that additional mechanisms also
      contribute to collaborative inhibition. In the current studies, we examined 2
      alternate mechanisms: retrieval inhibition and retrieval blocking. To identify
      the contributions of retrieval disruption, retrieval inhibition, and retrieval
      blocking, we tested how collaborative recall of entirely unshared information
      influences subsequent individual recall and individual recognition memory. If
      collaborative inhibition is due solely to retrieval disruption, then there should
      be a release from the negative effects of collaboration on subsequent individual
      recall and recognition tests. If it is due to retrieval inhibition, then the
      negative effects of collaboration should persist on both individual recall and
      recognition memory tests. Finally, if it is due to retrieval blocking, then the
      impairment should persist on subsequent individual free recall, but not
      recognition, tests. Novel to the current study, results suggest that retrieval
      inhibition plays a role in the collaborative inhibition effect. The negative
      effects of collaboration persisted on a subsequent, always-individual, free
      recall test (Experiment 1) and also on a subsequent, always-individual,
      recognition test (Experiment 2). However, consistent with the retrieval
      disruption account, this deficit was attenuated (Experiment 1). Together, these
      results suggest that, in addition to retrieval disruption, multiple mechanisms
      play a role in collaborative inhibition. (PsycINFO Database Record (c) 2015 APA,
      all rights reserved). 

PMID- 25068857
TI  - Time to decide? Simplicity and congruity in comparative judgment.
AB  - What is the relationship between magnitude judgments relying on directly
      available characteristics versus probabilistic cues? Question frame was
      manipulated in a comparative judgment task previously assumed to involve
      inference across a probabilistic mental model (e.g., "Which city is largest"--the
      "larger" question-vs. "Which city is smallest"--the "smaller" question).
      Participants identified either the largest or smallest city (Experiments 1a and
      2) or the richest or poorest person (Experiment 1b) in a 3-alternative forced
      choice (3-AFC) task (Experiment 1) or a 2-AFC task (Experiment 2). Response times
      revealed an interaction between question frame and the number of options
      recognized. When participants were asked the smaller question, response times
      were shorter when none of the options were recognized. The opposite pattern was
      found when participants were asked the larger question: response time was shorter
      when all options were recognized. These task-stimuli congruity results in
      judgment under uncertainty are consistent with, and predicted by, theories of
      magnitude comparison, which make use of deductive inferences from declarative
      knowledge.

PMID- 25068858
TI  - How does Stroop interference change with practice? A reappraisal from the musical
      Stroop paradigm.
AB  - Most earlier studies investigating the evolution of the Stroop effect with the
      amount of reading practice have reported data consistent with an inverted U
      shaped curve, whereby the Stroop effect appears early during reading acquisition,
      reaches a peak after 2 or 3 years of practice, and then continuously decreases
      until adulthood. The downward component of the curve suggests that skilled
      performers would be able to control their performance better than less-skilled
      performers. However, in these studies, the level of reading practice entirely
      coincides with age due to obvious practical and ethical constraints, and it is
      possible that the observed reduction in the Stroop interference is due to a
      growing ability of older children to inhibit nonrelevant information. In the
      present study, word reading, as source of interference, was replaced by note
      naming in musicians. The major advantage is that musical training can be easily
      decoupled from age. In 2 experiments exploiting the musical Stroop paradigm
      (Gregoire, Perruchet, & Poulin-Charronnat, 2013), we observed an early appearance
      of the interference effect, as reported for the color-word and picture-word
      Stroop tasks, but we did not replicate the inverted U-shaped curve. Experiment 2
      revealed a linear and positive relation between the amplitude of the musical
      Stroop effect and the amount of musical practice across 5 years of musical
      training. These results suggest that reading practice in itself does not lead to
      increased control over reading and that the usual pattern of results is most
      likely due to the strong correlation between age and reading practice.

PMID- 25068859
TI  - Isolating a mediated route for response congruency effects in task switching.
AB  - Response congruency effects in task switching reflect worse performance for
      incongruent targets associated with different responses across tasks than for
      congruent targets associated with the same response. In the present study, the
      author investigated whether the effects can be produced solely by a mediated
      route for response selection, whereby targets are categorized with respect to
      both tasks, as opposed to a nonmediated route, whereby target-response instances
      from past experience are retrieved directly from long-term memory. The mediated
      route was isolated in 3 experiments by having subjects perform semantic
      categorization tasks on targets that were never repeated, thereby making the
      nonmediated route nonfunctional. Robust response congruency effects were observed
      for both response time and error rate in all experiments, indicating that the
      mediated route is sufficient to produce such effects by itself. The results imply
      that subjects engaged in dual-task processing despite no requirement to do so,
      raising questions about the modeling of response selection in task-switching
      situations.

PMID- 25068860
TI  - Grain size of recall practice for lengthy text material: fragile and mysterious
      effects on memory.
AB  - The current research evaluated the extent to which the grain size of recall
      practice for lengthy text material affects recall during practice and subsequent
      memory. The grain size hypothesis states that a smaller vs. larger grain size
      will increase retrieval success during practice that in turn will enhance
      subsequent memory for lengthy text material. Participants were prompted to recall
      directly after studying each section (section recall) or after all sections had
      been studied (whole-text recall) during practice, and then all participants
      completed a final test after a delay. Results across 7 experiments (including 587
      participants and 1,394 recall protocols) partially disconfirmed the predictions
      of the grain size hypothesis: Although the smaller grain size produced sizable
      recall advantages during practice as expected (ds from 1.02 to 1.87 across
      experiments), the advantage was substantially or completely attenuated across a
      delay. Experiments 2-7 falsified several plausible methodological and theoretical
      explanations for the fragility of the effect, indicating that it was not due to
      particular text materials, retrieval from working memory during practice, the
      length of the retention interval, the spacing between study and practice recall,
      a disproportionate increase in recall of unimportant details, or a deficit in
      integration of ideas across text sections. In sum, results conclusively establish
      an initially sizable but mysteriously fragile effect of grain size, for which an
      explanation remains elusive.

PMID- 25068861
TI  - Rice hull smoke extract protects mice against a Salmonella lipopolysaccharide
      induced endotoxemia.
AB  - Endotoxemia (sepsis, septic shock) is an inflammatory, virulent disease that
      results mainly from infection by Gram-negative bacteria. The present study
      investigates the inhibitory effects of a rice hull smoke extract (RHSE) against
      murine endotoxemia induced by Salmonella lipopolysaccharide and d-galactosamine
      (LPS/GalN). Pretreatment of the mice with RHSE via dietary administration for 2
      weeks resulted in the suppression (in %) of LPS/GalN-induced catalase by 70.7,
      superoxide dismutase (SOD) by 54.6, and transaminase (GOT/GPT) liver enzymes by
      40.6/62.5, the amelioration of necrotic liver lesions, and the reduction of tumor
      necrosis factor-alpha (TNF-alpha) by 61.1 and nitrite serum level by 83.4, as
      well as myeloperoxidase (MPO) enzyme associated with necrotic injury of the lung
      and kidney by 65.7 and 63.3, respectively. The RHSE also extended the lifespan of
      the toxemic mice. The results using inflammation biomarkers and from the lifespan
      studies suggest that the RHSE can protect mice against LPS/GalN-induced liver,
      lung, and kidney injuries and inflammation by blocking oxidative stress and TNF
      alpha production, thereby increasing the survival of the toxic-shock-induced
      mice. These beneficial effects and previous studies on the antimicrobial effects
      against Salmonella Typhimurium in culture and in mice suggest that the smoke
      extract also has the potential to serve as a new multifunctional resource in
      human food and animal feeds. Possible mechanisms of the beneficial effects at the
      cellular and molecular levels and suggested food uses are discussed. 

PMID- 25068862
TI  - Disseminating ambient assisted living in rural areas.
AB  - The smart home, ambient intelligence and ambient assisted living have been
      intensively researched for decades. Although rural areas are an important
      potential market, because they represent about 80% of the territory of the EU
      countries and around 125 million inhabitants, there is currently a lack of
      applicable AAL solutions. This paper discusses the theoretical foundations of AAL
      in rural areas. This discussion is underlined by the achievements of the
      empirical field study, Casa Vecchia, which has been carried out over a four-year
      period in a rural area in Austria. The major goal of Casa Vecchia was to evaluate
      the feasibility of a specific form of AAL for rural areas: bringing AAL
      technology to the homes of the elderly, rather than moving seniors to special
      equipped care facilities. The Casa Vecchia project thoroughly investigated the
      possibilities, challenges and drawbacks of AAL related to this specific approach.
      The findings are promising and somewhat surprising and indicate that further
      technical, interactional and socio-psychological research is required to make AAL
      in rural areas reasonable in the future. 

PMID- 25068863
TI  - Near infrared spectroscopy calibration for wood chemistry: which chemometric
      technique is best for prediction and interpretation?
AB  - This paper addresses the precision in factor loadings during partial least
      squares (PLS) and principal components regression (PCR) of wood chemistry content
      from near infrared reflectance (NIR) spectra. The precision of the loadings is
      considered important because these estimates are often utilized to interpret
      chemometric models or selection of meaningful wavenumbers. Standard laboratory
      chemistry methods were employed on a mixed genus/species hardwood sample set. PLS
      and PCR, before and after 1st derivative pretreatment, was utilized for model
      building and loadings investigation. As demonstrated by others, PLS was found to
      provide better predictive diagnostics. However, PCR exhibited a more precise
      estimate of loading peaks which makes PCR better for interpretation. Application
      of the 1st derivative appeared to assist in improving both PCR and PLS loading
      precision, but due to the small sample size, the two chemometric methods could
      not be compared statistically. This work is important because to date most
      research works have committed to PLS because it yields better predictive
      performance. But this research suggests there is a tradeoff between better
      prediction and model interpretation. Future work is needed to compare PLS and PCR
      for a suite of spectral pretreatment techniques. 

PMID- 25068864
TI  - Two-level optical coherence tomography scheme for suppressing spectral saturation
      artifacts.
AB  - We demonstrate a novel method for reducing saturation artifacts in spectral
      domain optical coherence tomography (SD-OCT) systems. This method is based on a
      two-level SD-OCT system with a dual-line charge-coupled device (CCD) camera. We
      compensate the saturated signal detected by the first line using the unsaturated
      signal detected by the second line. The Fourier transform of the compensated
      spectrum shows effective suppression of saturation artifacts. This method was
      also successfully performed on phantom material and skin on a human finger. Our
      method causes neither back-scattering power loss nor signal-to-noise ratio (SNR)
      degradation. The only difference between the traditional system and our two-level
      system is our utilization of the dual-line CCD camera; no additional devices or
      complex designs are needed. 

PMID- 25068865
TI  - A comprehensive review of sensors and instrumentation methods in devices for
      musical expression.
AB  - Digital Musical Instruments (DMIs) are musical instruments typically composed of
      a control surface where user interaction is measured by sensors whose values are
      mapped to sound synthesis algorithms. These instruments have gained interest
      among skilled musicians and performers in the last decades leading to artistic
      practices including musical performance, interactive installations and dance. The
      creation of DMIs typically involves several areas, among them: arts, design and
      engineering. The balance between these areas is an essential task in DMI design
      so that the resulting instruments are aesthetically appealing, robust, and allow
      responsive, accurate and repeatable sensing. In this paper, we review the use of
      sensors in the DMI community as manifested in the proceedings of the
      International Conference on New Interfaces for Musical Expression (NIME 2009
      2013). Focusing on the sensor technologies and signal conditioning techniques
      used by the NIME community. Although it has been claimed that specifications for
      artistic tools are harder than those for military applications, this study raises
      a paradox showing that in most of the cases, DMIs are based on a few basic
      sensors types and unsophisticated engineering solutions, not taking advantage of
      more advanced sensing, instrumentation and signal processing techniques that
      could dramatically improve their response. We aim to raise awareness of
      limitations of any engineering solution and to assert the benefits of advanced
      electronics instrumentation design in DMIs. For this, we propose the use of
      specialized sensors such as strain gages, advanced conditioning circuits and
      signal processing tools such as sensor fusion. We believe that careful electronic
      instrumentation design may lead to more responsive instruments. 

PMID- 25068867
TI  - Perioperative management of tonsilloadenoidectomy and circumcision of a patient
      with Bernard-Soulier syndrome: case report.
AB  - Bernard-Soulier syndrome is an autosomal recessive coagulopathy characterized by
      thrombocytopenia, prolonged bleeding time and large platelets. Because of the
      rarity of this disease, standard perioperative treatment protocols have not been
      developed and there are not enough available data for the management of surgical
      procedures. In this case, we successfully performed adenoidectomy and
      tonsillectomy and circumcision surgery concurrently under the preventive and
      intermittent transfusion of platelets. During hospitalization, no intraoperative
      or postoperative bleeding complications occurred. 

PMID- 25068866
TI  - Virus outbreaks in chemical and biological sensors.
AB  - Filamentous bacteriophages have successfully been used to detect chemical and
      biological analytes with increased selectivity and sensitivity. The enhancement
      largely originates not only from the ability of viruses to provide a platform for
      the surface display of a wide range of biological ligands, but also from the
      geometric morphologies of the viruses that constitute biomimetic structures with
      larger surface area-to-volume ratio. This review will appraise the mechanism of
      multivalent display of the viruses that enables surface modification of virions
      either by chemical or biological methods. The accommodation of functionalized
      virions to various materials, including polymers, proteins, metals,
      nanoparticles, and electrodes for sensor applications will also be discussed. 

PMID- 25068868
TI  - Phase differences in expression of circadian clock genes in the central nucleus
      of the amygdala, dentate gyrus, and suprachiasmatic nucleus in the rat.
AB  - We performed a high temporal resolution analysis of the transcript level of two
      core clock genes, Period2 (Per2) and Bmal1, and a clock output gene, Dbp, in the
      suprachiasmatic nucleus (SCN), the master circadian clock, and in two forebrain
      regions, the lateral part of the central nucleus of the amygdala (CEAl), and
      dentate gyrus (DG), in rats. These regions, as we have shown previously, exhibit
      opposite rhythms in expression of the core clock protein, PERIOD2 (PER2). We
      found that the expression of Per2, Bmal1 and Dbp follow a diurnal rhythm in all
      three regions but the phase and amplitude of the rhythms of each gene vary across
      regions, revealing important regional differences in temporal dynamics underlying
      local daily rhythm generation in the mammalian forebrain. These findings
      underscore the complex temporal organization of subordinate circadian oscillators
      in the forebrain and raise interesting questions about the functional connection
      of these oscillators with the master SCN clock. 

PMID- 25068869
TI  - Increased drought impacts on temperate rainforests from southern South America:
      results of a process-based, dynamic forest model.
AB  - Increased droughts due to regional shifts in temperature and rainfall regimes are
      likely to affect forests in temperate regions in the coming decades. To assess
      their consequences for forest dynamics, we need predictive tools that couple
      hydrologic processes, soil moisture dynamics and plant productivity. Here, we
      developed and tested a dynamic forest model that predicts the hydrologic balance
      of North Patagonian rainforests on Chiloe Island, in temperate South America (42
      degrees S). The model incorporates the dynamic linkages between changing rainfall
      regimes, soil moisture and individual tree growth. Declining rainfall, as
      predicted for the study area, should mean up to 50% less summer rain by year
      2100. We analysed forest responses to increased drought using the model proposed
      focusing on changes in evapotranspiration, soil moisture and forest structure
      (above-ground biomass and basal area). We compared the responses of a young stand
      (YS, ca. 60 years-old) and an old-growth forest (OG, >500 years-old) in the same
      area. Based on detailed field measurements of water fluxes, the model provides a
      reliable account of the hydrologic balance of these evergreen, broad-leaved
      rainforests. We found higher evapotranspiration in OG than YS under current
      climate. Increasing drought predicted for this century can reduce
      evapotranspiration by 15% in the OG compared to current values. Drier climate
      will alter forest structure, leading to decreases in above ground biomass by 27%
      of the current value in OG. The model presented here can be used to assess the
      potential impacts of climate change on forest hydrology and other threats of
      global change on future forests such as fragmentation, introduction of exotic
      tree species, and changes in fire regimes. Our study expands the applicability of
      forest dynamics models in remote and hitherto overlooked regions of the world,
      such as southern temperate rainforests. 

PMID- 25068871
TI  - Gradient-based high precision alignment of cryo-electron subtomograms.
AB  - Whole cell cryo-electron tomography emerges as an important component for
      structural system biology approaches. It allows the localization and structural
      characterization of macromolecular complexes in near living conditions. However,
      the method is hampered by low resolution, missing data and low signal-to-noise
      ratio (SNR). To overcome some of these difficulties one can align and average a
      large set of subtomograms. Existing alignment methods are mostly based on an
      exhaustive scanning and sampling of all but discrete relative rotations and
      translations of one subtomogram with respect to the other. In this paper, we
      propose a gradient-guided alignment method based on two subtomogram similarity
      measures. We also propose a stochastic parallel optimization that increases
      significantly the efficiency for the simultaneous refinement of a set of
      alignment candidates. Results on simulated data of model complexes and
      experimental structures of protein complexes show that even for highly distorted
      subtomograms and with only a small number of very sparsely distributed initial
      alignment seeds, our method can accurately recover true transformations with a
      significantly higher precision than scanning based alignment methods.

PMID- 25068870
TI  - Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin
      dependent mechanism.
AB  - General anesthetics produce a reversible coma-like state through modulation of
      excitatory and inhibitory synaptic transmission. Recent evidence suggests that
      anesthetic exposure can also lead to sustained cognitive dysfunction. However,
      the subcellular effects of anesthetics on the structure of established synapses
      are not known. We investigated effects of the widely used volatile anesthetic
      isoflurane on the structural stability of hippocampal dendritic spines, a
      postsynaptic structure critical to excitatory synaptic transmission in learning
      and memory. Exposure to clinical concentrations of isoflurane induced rapid and
      non-uniform shrinkage and loss of dendritic spines in mature cultured rat
      hippocampal neurons. Spine shrinkage was associated with a reduction in spine F
      actin concentration. Spine loss was prevented by either jasplakinolide or
      cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine
      shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane
      destabilizes spine F-actin, resulting in changes to dendritic spine morphology
      and number. These findings support an actin-based mechanism for isoflurane
      induced alterations of synaptic structure in the hippocampus. These reversible
      alterations in dendritic spine structure have important implications for acute
      anesthetic effects on excitatory synaptic transmission and synaptic stability in
      the hippocampus, a locus for anesthetic-induced amnesia, and have important
      implications for anesthetic effects on synaptic plasticity. 

PMID- 25068872
TI  - Change, people, and the bottom line.

PMID- 25068873
TI  - Enhancing learning, innovation, adaptation, and sustainability in health care
      organizations: the ELIAS performance management framework.
AB  - The development of sustainable health care organizations that provide high
      quality accessible care is a topic of intense interest. This article provides a
      practical performance management framework that can be utilized to develop
      sustainable health care organizations. It is a cyclical 5-step process that is
      premised on accountability, performance management, and learning practices that
      are the foundation for a continuous process of measurement, disconfirmation,
      contextualization, implementation, and routinization This results in the
      enhancement of learning, innovation, adaptation, and sustainability (ELIAS).
      Important considerations such as recognizing that health care organizations are
      complex adaptive systems and the presence of a dynamic learning culture are
      necessary contextual factors that maximize the effectiveness of the proposed
      framework. Importantly, the ELIAS framework utilizes data that are already being
      collected by health care organizations for accountability, improvement,
      evaluation, and strategic purposes. Therefore, the benefit of the framework, when
      used as outlined, would be to enhance the chances of health care organizations
      achieving the goals of ongoing adaptation and sustainability, by design, rather
      than by chance. 

PMID- 25068875
TI  - New York's Health Care Workforce Recruitment and Retention Act: an investigation
      of the effects of nonrecurring increases in health worker wage on health worker
      supply.
AB  - This article analyzes New York's Health Care Workforce Recruitment and Retention
      Act of 2002. The analysis comes in 4 parts: part 1 provides a brief overview of
      New York's economy as it relates to health care, a feel for the political climate
      at the time, and a detailed presentation of the chain of events that connect this
      climate to the birth of the Health Care Workforce Recruitment and Retention Act
      of 2002; part 2 consists of a breakdown of the provisions contained within bill,
      including major and minor goals, intended effects, and the mechanics behind
      raising supporting funds; part 3 explores what actually happened by evaluating
      available data to determine whether the bill's 2 major goals of workforce
      recruitment and retention were fulfilled; and finally, part 4 will take all the
      aforementioned information to determine the overall success of the bill, the
      implications, and specific suggestions for future policy changes that time has
      revealed since its inception. 

PMID- 25068874
TI  - Analysis and recommendations for reducing risks of patient crosscontaminations
      via noncritical medical devices.
AB  - Based on the serious problem of health care-associated infections and the
      understanding that patient crosscontamination is essentially preventable,
      opinions were sought from health care providers for insight into likely sources
      of crosscontamination in US hospitals, probable causes, and areas for additional
      investigation. Respondents indicated that inadequate disinfection of noncritical,
      patient care devices pose an underrecognized threat to patient
      crosscontamination. This led the researchers to question reliance upon the
      current Centers for Disease Control and Prevention (CDC) Guideline for
      Disinfection and Sterilization in Healthcare Facilities for such items. The CDC
      Guideline follows the Spaulding approach, which categorizes items and their
      disinfection treatment based on the risk of infection from the intended use of
      the item. A failure modes, effects, and criticality analysis approach is
      recommended as an additional refinement to the CDC Guideline whereby likely
      sources of cross-contamination are identified irrespective of intended use.
      Enhancing infection control practices with this approach promotes the development
      of preventive plans for cleaning and disinfection that can mitigate such risk. 

PMID- 25068876
TI  - Dimensions of quality care affecting career satisfaction of pediatricians.
AB  - This study investigated factors impacting career satisfaction among
      pediatricians. The study used data from the 2008 Health Tracking Physician
      Survey, conducted by the Center for Studying Health System Change. The 2008
      Health Tracking Physician Survey data set consisted of 4720 physicians who were
      members of the American Medical Association. Among the respondents, 427
      identified themselves as pediatricians. Results indicated more than 52% of
      pediatricians were very satisfied with their careers in medicine. Nearly 35% of
      pediatricians were older than 48 years. Approximately 48% were male, and 67% were
      of white race. The average respondent worked 45 hours per week in medically
      related activities. Regression analysis indicated the following had a significant
      impact on pediatrician career satisfaction: inadequate time with patients,
      patient noncompliance, and delayed reports from other physicians and facilities.
      Number of hours worked per week and worry over potential malpractice suits also
      had a significant impact on career satisfaction of pediatricians. 

PMID- 25068878
TI  - Foundation of evidence-based decision making for health care managers-part II:
      meta-analysis and applying the evidence.
AB  - This article is a continuation of a 2-part series that seeks to build the skills
      of health care managers and supervisors in critically reading and interpreting
      systematic reviews and meta-analyses. The first article, part I, defined the
      types of systematic reviews and outlined the process of conducting them. This
      article, part II, focuses on meta-analysis, a type of systematic review. This
      article explains the additional procedures associated with meta-analyses and
      describes the potential shortcomings of both systematic reviews and meta
      analyses. Finally, this article provides a way for health care managers and
      supervisors to appraise systematic reviews and meta-analyses and to determine
      whether the evidence applies to their problems and settings. 

PMID- 25068879
TI  - Foreign-trained nurses' experiences and socioprofessional integration best
      practices: an integrative literature review.
AB  - This article examines the evidence available on obstacles and facilitating
      factors for the socioprofessional integration of internationally educated nurses
      (IENs) and tries to generate best practices concerning their workforce
      integration. In the nursing shortage context, more and more attention is given to
      IEN recruitment. Still, IENs' integration experiences into their new environment
      are strenuous. Differences in nursing practice and in cultural values,
      communicational barriers, discrimination, and competency recognition delays
      complicate this transition. Yet few guidelines are found concerning the best
      practices to implement to ease this process. This literature review suggests the
      necessity for a collaborative approach of IEN integration. 

PMID- 25068880
TI  - Medicare fraud in the United States: can it ever be stopped?
AB  - The majority of the United States health care fraud has been focused on the major
      public program, Medicare. The yearly financial loss from Medicare fraud has been
      estimated at about $54 billion. The purpose of this research study was to explore
      the current state of Medicare fraud in the United States, identify current
      policies and laws that foster Medicare fraud, and determine the financial impact
      of Medicare fraud. The methodology for this study was a literature review.
      Research was conducted using a scholarly online database search and government
      Web sites. The number of individuals charged with criminal fraud increased from
      797 cases in fiscal year 2008 to 1430 cases in fiscal year 2011-an increase of
      more than 75%. According to 2010 data, of the 7848 subjects investigated for
      criminal fraud, 25% were medical facilities, and 16% were medical equipment
      suppliers. In 2009 and 2010, the Health Care Fraud and Abuse Control Program
      recovered approximately $25.2 million of taxpayers' money. Educating providers
      about the policies and laws designed to prevent fraud would help them to become
      partners. Many new programs and partnerships with government agencies have also
      been developed to combat Medicare fraud. Medicare fraud has been a persistent
      crime, and laws and policies alone have not been enough to control the problem.
      With investments in governmental partnerships and new systems, the United States
      can reduce Medicare fraud but probably will not stop it altogether. 

PMID- 25068881
TI  - Factors influencing consumer satisfaction with health care.
AB  - The purpose of this study was to examine factors that impact consumer
      satisfaction with health care. This is a secondary analysis of the Center for
      Studying Health System Change's 2010 Health Tracking Household Survey. Regression
      analysis was used to examine the impact of treatment issues, financial issues,
      family-related issues, sources of health care information, location, and
      demographics-related factors on satisfaction with health care. The study involved
      12280 subjects, 56% of whom were very satisfied with their health care, whereas
      66% were very satisfied with their primary care physician. Fourteen percent of
      the subjects had no health insurance; 34% of the subjects got their health care
      information from the Web. Satisfaction with primary care physician, general
      health status, promptness of visit to doctor, insurance type, medical cost per
      family, annual income, persons in family, health care information from friends,
      and age significantly impacted satisfaction with health care. The regression
      models accounted for 23% of the variance in health care satisfaction.
      Satisfaction with primary care physicians, health insurance, and general health
      status are the 3 most significant indicators of an individual's satisfaction with
      health care.

PMID- 25068882
TI  - The Affordable Care Act: the ethical call to transform the organizational
      culture.
AB  - The Patient Protection and Affordable Care Act will require health care leaders
      and managers to develop strategies and implement organizational tactics for their
      organization to survive and thrive under the federal mandates of this new health
      care law. Successful health care organizations and health care systems will be
      defined by their adaptability in the new value-based marketplace created by the
      Affordable Care Act. The most critical underlining challenge for this success
      will be the effective transformation of the organizational culture.
      Transformational value-based leadership is now needed to answer the ethical call
      for transforming the organizational culture. This article provides a model and
      recommendations to influence change in the most difficult leadership duty
      transforming the organizational culture. 

PMID- 25068883
TI  - Biomonitoring Equivalents for selenium.
AB  - Selenium is an essential nutrient for human health with a narrow range between
      essentiality and toxicity. Selenium is incorporated into several proteins that
      perform important functions in the body. With insufficient selenium intake, the
      most notable effect is Keshan disease, an endemic cardiomyopathy in children.
      Conversely, excessive selenium intake can result in selenosis, manifested as
      brittle nails and hair and gastro-intestinal disorders. As such, guidance values
      have been established to protect against both insufficient and excessive selenium
      exposures. Dietary Reference Intakes (DRIs) have been established as standard
      reference values for nutritional adequacy in North America. To protect against
      selenosis resulting from exposure to excessive amounts of selenium, several
      government and non-governmental agencies have established a range of guidance
      values. Exposure to selenium is primarily through the diet, but monitoring
      selenium intake is difficult. Biomonitoring is a useful means of assessing and
      monitoring selenium status for both insufficient and excessive exposures.
      However, to be able to interpret selenium biomonitoring data, levels associated
      with both DRIs and toxicity guidance values are required. Biomonitoring
      Equivalents (BEs) were developed for selenium in whole blood, plasma and urine.
      The BEs associated with assuring adequate selenium intake (Estimated Average
      Requirements - EAR) are 100, 80 and 10MUg/L in whole blood, plasma and urine,
      respectively. The BEs associated with protection against selenosis range from 400
      to 480MUg/L in whole blood, 180-230MUg/L in plasma, and 90-110MUg/L in urine.
      These BE values can be used by both regulatory agencies and public health
      officials to interpret selenium biomonitoring data in a health risk context. 

PMID- 25068884
TI  - Bovine colostrum, training status, and gastrointestinal permeability during
      exercise in the heat: a placebo-controlled double-blind study.
AB  - Heat stress can increase gastrointestinal permeability, allowing ingress of gram
      negative bacterial fragments and thus potentially inflammation and ultimately
      endotoxemia. Permeability may rise with intense exercise, yet some data indicate
      that endotoxemia may be mitigated with bovine colostrum supplementation. Using a
      double-blind, randomised, placebo-controlled crossover study, we tested whether
      bovine colostrum (COL; 1.7 g.kg(-1).day(-1) for 7 days) would attenuate
      physiological strain and aid exercise capacity in the heat, especially in
      untrained individuals. Seven trained men (T; peak oxygen uptake 64 +/- 4 mL.kg(
      1).min(-1)) and 8 untrained men (UT, peak oxygen uptake 46 +/- 4 mL.kg(-1).min(
      1)) exercised for 90 min in 30  degrees C (50 % relative humidity) after COL or
      placebo (corn flour). Exercise consisted of 15-min cycling at 50 % heart rate
      reserve (HRR) before and after 60 min of running (30 min at 80 % HRR then 30-min
      distance trial). Heart rate, blood pressure (Finometer), esophageal, and skin
      temperatures were recorded continuously. Gastrointestinal permeability was
      assessed from urine (double-sugar model, using high-performance liquid
      chromatography) and blood (intestinal fatty acid-binding protein, I-FABP). The T
      group ran ~2.4 km (35%) further than the UT group in the distance trial, and I
      FABP increased more in the T group than in the UT group, but physiological and
      performance outcomes were unaffected by colostrum supplementation, irrespective
      of fitness. Circulating pro- and anti-inflammatory cytokine concentrations were
      higher following exercise, but were not modulated by fitness or COL. Despite
      substantial thermal and cardiovascular strain incurred in environmental
      conditions in which exertional endotoxemia may occur, bovine colostrum
      supplementation had no observable benefit on the physiology or performance of
      either highly trained endurance athletes or untrained individuals. 

PMID- 25068885
TI  - A systems biology-based approach to uncovering the molecular mechanisms
      underlying the effects of dragon's blood tablet in colitis, involving the
      integration of chemical analysis, ADME prediction, and network pharmacology.
AB  - Traditional Chinese medicine (TCM) is one of the oldest East Asian medical
      systems. The present study adopted a systems biology-based approach to provide
      new insights relating to the active constituents and molecular mechanisms
      underlying the effects of dragon's blood (DB) tablets for the treatment of
      colitis. This study integrated chemical analysis, prediction of absorption,
      distribution, metabolism, and excretion (ADME), and network pharmacology.
      Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography
      electrospray ionization-tandem mass spectrometry method was employed to identify
      48 components of DB tablets. In silico prediction of the passive absorption of
      these compounds, based on Caco-2 cell permeability, and their P450 metabolism
      enabled the identification of 22 potentially absorbed components and 8
      metabolites. Finally, networks were constructed to analyze interactions between
      these DB components/metabolites absorbed and their putative targets, and between
      the putative DB targets and known therapeutic targets for colitis. This study
      provided a great opportunity to deepen the understanding of the complex
      pharmacological mechanisms underlying the effects of DB in colitis treatment. 

PMID- 25068886
TI  - Ageing-related responses to antiangiogenic effects of sunitinib in
      atherosclerosis-prone mice.
AB  - Antiangiogenic therapies in cancer exert their effects in the context of age
      related comorbidities, which affect the entirety of the vascular system. Among
      those conditions, the impact of atherosclerosis is especially prevalent, but
      poorly understood, and not reflected in mouse models routinely used for testing
      antiangiogenic therapeutics. Our earlier work suggested that these obstacles can
      be overcome with the use of atherosclerosis-prone ApoE-/- mice harbouring
      syngeneic transplantable Lewis Lung Carcinoma (LLC). Here we report that,
      sunitinib, the clinically approved, antiangiogenic inhibitor impedes global tumor
      growth to a greater extent in aged then in young mice. This activity was coupled
      with changes in the tumor microenvironment, which in aged mice was characterized
      by pronounced hypoxia, reduction in microvascular density (MVD) and lower
      pericyte coverage, relative to young controls. We also detected soluble VEGR2 in
      plasma of sunitinib treated mice. Interestingly, sunitinib modulated tumor
      infiltration with bone marrow-derived cells (CD45+), recruitment of M2-like
      macrophages (CD163+) and activation of inflammatory pathways (phospho-STAT3) in a
      manner that was age-dependent. We suggest that age and atherosclerosis may alter
      the effects of sunitinib on the tumor microenvironment, and that these
      considerations may also apply more broadly to other forms of antiangiogenic
      treatment in cancer. 

PMID- 25068887
TI  - Stretchable carbon nanotube/ion-gel supercapacitors with high durability realized
      through interfacial microroughness.
AB  - A critical problem with stretchable supercapacitors developed to date has been
      evaporation of a volatile component of their electrolyte, causing failure. In
      this work, we demonstrated successful use of an ionic-liquid-based nonvolatile
      gel (ion-gel) electrolyte in carbon nanotube (CNT)-based stretchable
      supercapacitors. The CNT/ion-gel supercapacitors showed high capacitance
      retention (96.6%) over 3000 stretch cycles at 20% strain. The high durability
      against stretch cycles was achieved by introducing microroughness at the
      interfaces between different materials. The microroughness was produced by the
      simple process of imprinting the surface microstructure of office paper onto a
      poly(dimethylsiloxane) substrate; the surface texture is reproduced in successive
      current collector and CNT layers. Adhesion between the different layers was
      strengthened by this roughness and prevented delamination over repeated stretch
      cycles. The addition of a CNT layer decreased the sensitivity of electrical
      characteristics to stretching. Moreover, the ion-gel increases the operating
      voltage window (3 V) and hence the energy density. We believe our demonstration
      will greatly contribute to the development of flexible and/or stretchable energy
      storage devices with high durability. 

PMID- 25068888
TI  - Novel functionalization of discrete polymeric biomaterial microstructures for
      applications in imaging and three-dimensional manipulation.
AB  - Adapting ways to functionalize polymer materials is becoming increasingly
      important to their implementation in translational biomedical sciences. By tuning
      the mechanical, chemical, and biological qualities of these materials, their
      applications can be broadened, opening the door for more advanced integration
      into modern medical techniques. Here, we report on a method to integrate chemical
      functionalizations into discrete, microscale polymer structures, which are used
      for tissue engineering applications, for in vivo localization, and three
      dimensional manipulation. Iron oxide nanoparticles were incorporated into the
      polymer matrix using common photolithographic techniques to create stably
      functional microstructures with magnetic potential. Using magnetic resonance
      imaging (MRI), we can promote visualization of microstructures contained in small
      collections, as well as facilitate the manipulation and alignment of
      microtopographical cues in a realistic tissue environment. Using similar polymer
      functionalization techniques, fluorine-containing compounds were also embedded in
      the polymer matrix of photolithographically fabricated microstructures. The
      incorporation of fluorine-containing compounds enabled highly sensitive and
      specific detection of microstructures in physiologic settings using fluorine MRI
      techniques ((19)F MRI). These functionalization strategies will facilitate more
      reliable noninvasive tracking and characterization of microstructured polymer
      implants as well as have implications for remote microstructural scaffolding
      alignment for three-dimensional tissue engineering applications. 

PMID- 25068889
TI  - Mechlorethamine gel for the topical treatment of stage IA and IB mycosis
      fungoides-type cutaneous T-cell lymphoma.
AB  - Mycosis fungoides (MF) is an extranodal non-Hodgkins lymphoma of T-cell origin.
      MF is the most common type and can be stratified as early (IA-IIA) or late (IIB
      or greater) stage disease. Patients with patch disease usually have a benign,
      chronic course. Patients with plaques have a worse prognosis and need more
      aggressive therapy. Topical nitrogen mustard ([NM]; mechlorethamine
      hydrochloride) has been used for MF since the 1950s. Complete response rates
      reported for stage IA are 76-80% and 35-68% for stage IB. Most common toxicities
      reported are irritant contact dermatitis, allergic reaction and
      hyperpigmentation. There is a potential for risk of non-melanoma skin cancers
      reported with NM use in patients who used multiple skin damaging therapies. This
      article focuses on the clinical trial that led to the US FDA approval of VALCHLOR
      for stage IA and IB MF in 2013 after one prior treatment (excluding NM within 2
      years or carmustine therapy ever).

PMID- 25068890
TI  - Analysis of surgically induced astigmatism on the posterior surface of the
      cornea.
AB  - PURPOSE: To measure surgically induced astigmatism (SIA) on the posterior surface
      of the cornea using Scheimpflug-based keratometry on eyes with with-the-rule
      astigmatism. METHODS: Repeated Scheimpflug-based keratometry was obtained
      preoperatively and a mean of 8.65 weeks postoperatively following superior clear
      corneal incisions. Differences in the keratometric values and SIA were determined
      on the anterior and posterior surfaces separately and the data were analyzed.
      RESULTS: The study included 88 eyes of 88 patients (age range: 46.4 to 87.5
      years), with the steepest total corneal meridian between 75 degrees  and 105
      degrees . Preoperatively, the magnitude of the anterior and posterior corneal
      astigmatism was 0.74 +/- 0.44 and 0.29 +/- 0.14 diopters (D), respectively, which
      was greater than 0.5 D in 10 eyes (11.36%). The difference between preoperative
      and postoperative keratometric data on the posterior surface was significant, as
      was the difference between the preoperative and postoperative posterior
      astigmatism. The mean magnitude of posterior corneal SIA was 0.32 +/- 0.29 D,
      which was 0.5 D or greater in 22 eyes (25.00%). A statistically significant
      correlation was observed between the diopter of the preoperatively measured
      posterior corneal astigmatism and the postoperative SIA on the posterior surface
      (r = 0.34, P = .001). The correlation was not significant between SIA on the
      anterior and posterior surfaces (r = 0.10, P = .36). CONCLUSIONS: SIA on the
      posterior surface of the cornea may have a significant role, especially in cases
      of toric intraocular lens implantation. Posterior corneal astigmatism and SIA may
      have a significant clinical impact on more precise planning of cataract
      surgeries.

PMID- 25068891
TI  - Editorial: Sex matters in preclinical research.

PMID- 25068892
TI  - ERK oscillation-dependent gene expression patterns and deregulation by stress
      response.
AB  - Studies were undertaken to determine whether extracellular signal regulated
      kinase (ERK) oscillations regulate a unique subset of genes in human
      keratinocytes and subsequently whether the p38 stress response inhibits ERK
      oscillations. A DNA microarray identified many genes that were unique to ERK
      oscillations, and network reconstruction predicted an important role for the
      mediator complex subunit 1 (MED1) node in mediating ERK oscillation-dependent
      gene expression. Increased ERK-dependent phosphorylation of MED1 was observed in
      oscillating cells compared to nonoscillating counterparts as validation.
      Treatment of keratinocytes with a p38 inhibitor (SB203580) increased ERK
      oscillation amplitudes and MED1 and phospho-MED1 protein levels. Bromate is a
      probable human carcinogen that activates p38. Bromate inhibited ERK oscillations
      in human keratinocytes and JB6 cells and induced an increase in phospho-p38 and a
      decrease in phospho-MED1 protein levels. Treatment of normal rat kidney cells and
      primary salivary gland epithelial cells with bromate decreased phospho-MED1
      levels in a reversible fashion upon treatment with p38 inhibitors (SB202190;
      SB203580). Our results indicate that oscillatory behavior in the ERK pathway
      alters homeostatic gene regulation patterns and that the cellular response to
      perturbation may manifest differently in oscillating vs nonoscillating cells. 

PMID- 25068893
TI  - Synthesis and structure-activity relationships of pteridine dione and trione
      monocarboxylate transporter 1 inhibitors.
AB  - Novel substituted pteridine-derived inhibitors of monocarboxylate transporter 1
      (MCT1), an emerging target for cancer therapy, are reported. The activity of
      these compounds as inhibitors of lactate transport was confirmed using a (14)C
      lactate transport assay, and their potency against MCT1-expressing human tumor
      cells was established using MTT assays. The four most potent compounds showed
      substantial anticancer activity (EC50 37-150 nM) vs MCT1-expressing human Raji
      lymphoma cells. 

PMID- 25068895
TI  - Translocation mechanism of P-glycoprotein and conformational changes occurring at
      drug-binding site: Insights from multi-targeted molecular dynamics.
AB  - P-glycoprotein (P-gp) is well known for multidrug resistance in drug therapy. Its
      over-expression results into the increased efflux of therapeutic agents rendering
      them inefficacious. A clear understanding of P-gp efflux mechanism and
      substrate/inhibitor interactions during the course of efflux cycle will be
      crucial for designing effective P-gp inhibitors, and therapeutic agents that are
      non-substrate to P-gp. In the present work, we have modeled P-gp in three
      different catalytic states. These models were utilized for elucidation of P-gp
      translocation mechanism using multi-targeted molecular dynamics (MTMD). The
      gradual changes occurring in P-gp structure from inward open to outward open
      conformation were sampled out. A detailed investigation of conformational changes
      occurring in trans-membrane domains (TMDs) during the course of catalytic cycle
      was carried out. Movements of each TM helices in response to pronounced twisting
      and translatory motion of NBDs were measured quantitatively. The role of
      intracellular coupling helices (ICHs) during the structural transition of P-gp
      was studied, and observed as vital links for structural transition. A close
      observation of displacements and conformational changes in the residues lining
      drug-binding pocket was also carried out. Further, we have analyzed the molecular
      interactions of P-gp substrates/inhibitors during the P-gp translocation to find
      out how stable binding interactions of a compound at drug-binding site(s) in open
      conformation, becomes highly destabilized in closed conformation. The study
      revealed striking differences between the molecular interactions of substrate and
      inhibitor; inhibitors showed a tendency to maintain stable binding interactions
      during the catalytic transition cycle. 

PMID- 25068894
TI  - Awareness, treatment, control of diabetes mellitus and the risk factors: survey
      results from northeast China.
AB  - BACKGROUND: The awareness, treatment and control of diabetes mellitus (DM) can
      effectively reflect on the social status of diabetes conditions. Although several
      researchers have investigated the awareness, treatment and control rates of
      diabetes mellitus in China, little is known about their association with risk
      factors. This study aims to examine the relationship between risk factors and
      awareness, treatment and control of diabetes mellitus in northeast China.
      METHODS: A cross-sectional survey was conducted in 2012. Multistage stratified
      random cluster sampling design was used to select participants aged 18 to 79
      years old. The analysis was based on a representative sample of 1,854 adult
      subjects. Multivariable logistic regression analysis was used to examine socio
      demographic factors associated with the levels of awareness, treatment and
      control of diabetes mellitus. RESULTS: The awareness, treatment, and control
      rates of diabetes mellitus were 64.1%, 52.9% and 44.2%, respectively. In the
      multivariable logistic regression analysis, family history of diabetes was
      significantly positively associated with awareness (OR, 2.145; 95% CI, 1.600
      2.875) and treatment (OR, 2.021; 95% CI, 1.559-2.619) of diabetes mellitus, while
      negatively associated with control (OR, 0.671; 95% CI, 0.529-0.951). Cigarette
      smokers and alcohol drinkers were less likely than non-smokers and non-drinkers
      to be aware of their blood glucose levels (OR, 0.895, 0.614; 95% CI, 0.659-1.216,
      0.446-0.844, respectively). Participants who frequently exercise were more likely
      to be aware of their diabetic conditions than people who never or rarely exercise
      (OR, 2.003; 95% CI, 1.513-2.651). CONCLUSIONS: We found that the awareness and
      treatment of diabetes mellitus were positively associated with age and were high
      in participants with a family history of diabetes and those who exercise
      frequently, but low for cigarette smokers and alcohol drinkers. Participants with
      a family history of diabetes had their diabetic condition poorly controlled.

PMID- 25068896
TI  - Molecular-level characterization of elastin-like constructs and human aortic
      elastin.
AB  - This study aimed to characterize the structures of two elastin-like constructs,
      one composed of a cross-linked elastin-like polypeptide and the other one of
      cross-linked tropoelastin, and native aortic elastin. The structures of the
      insoluble materials and human aortic elastin were investigated using scanning
      electron microscopy. Additionally, all samples were digested with enzymes of
      different specificities, and the resultant peptide mixtures were characterized by
      ESI mass spectrometry and MALDI mass spectrometry. The MS(2) data was used to
      sequence linear peptides, and cross-linked species were analyzed with the
      recently developed software PolyLinX. This enabled the identification of two
      intramolecularly cross-linked peptides containing allysine aldols in the two
      constructs. The presence of the tetrafunctional cross-link desmosine was shown
      for all analyzed materials and its quantification revealed that the cross-linking
      degree of the two in vitro cross-linked materials was significantly lower than
      that of native elastin. Molecular dynamics simulations were performed, based on
      molecular species identified in the samples, to follow the formation of elastin
      cross-links. The results provide evidence for the significance of the GVGTP hinge
      region of domain 23 for the formation of elastin cross-links. Overall, this work
      provides important insight into structural similarities and differences between
      elastin-like constructs and native elastin. Furthermore, it represents a step
      toward the elucidation of the complex cross-linking pattern of mature elastin. 

PMID- 25068900
TI  - Technology and behavioural health: an implementation challenge.

PMID- 25068899
TI  - Gene silencing mediated by endogenous microRNAs under heat stress conditions in
      mammalian cells.
AB  - Heat shock, sudden change in temperature, triggers various responses in cells for
      protecting the cells from such a severe circumstance. Here we investigated gene
      silencing mediated by endogenous microRNAs (miRNAs) in mammalian cells exposed to
      a mild hyperthermia, by means of miRNA activity assay using a luciferase reporter
      gene as well as miRNA expression analysis using a DNA microarray. Our findings
      indicated that the gene silencing activities involving miRNAs were enhanced
      without increasing in their expression levels under heat-stress conditions.
      Additionally, the gene silencing activity appeared to be independent of the
      cytoprotective action involving heat shock proteins that are immediately
      activated in heat-shocked cells and that function as molecular chaperons for
      restoring heat-denatured proteins to normal proteins. Our current findings
      suggested the possibility that gene silencing involving endogenous miRNAs might
      play a subsidiary role in heat-shocked cells for an aggressive inhibition of the
      expression of heat-denatured proteins. 

PMID- 25068902
TI  - Simulation of the landfall of the Deepwater Horizon oil on the shorelines of the
      Gulf of Mexico.
AB  - We conducted simulations of oil transport from the footprint of the Macondo Well
      on the water surface throughout the Gulf of Mexico, including deposition on the
      shorelines. We used the U.S. National Oceanic Atmospheric Administration (NOAA)
      model General NOAA Operational Modeling Environment (GNOME) and the same
      parameter values and input adopted by NOAA following the Deepwater Horizon (DWH)
      blowout. We found that the disappearance rate of oil off the water surface was
      most likely around 20% per day based on satellite-based observations of the
      disappearance rate of oil detected on the sea surface after the DWH wellhead was
      capped. The simulations and oil mass estimates suggest that the mass of oil that
      reached the shorelines was between 10,000 and 30,000 tons, with an expected value
      of 22,000 tons. More than 90% of the oil deposition occurred on the Louisiana
      shorelines, and it occurred in two batches. Simulations revealed that capping the
      well after 2 weeks would have resulted in only 30% of the total oil depositing on
      the shorelines, while capping after 3 weeks would have resulted in 60%
      deposition. Additional delay in capping after 3 weeks would have averted little
      additional shoreline oiling over the ensuing 4 weeks.

PMID- 25068901
TI  - Maintenance or collapse: responses of extraplastidic membrane lipid composition
      to desiccation in the resurrection plant Paraisometrum mileense.
AB  - Resurrection plants usually grow in specific or extreme habitats and have the
      capacity to survive almost complete water loss. We characterized the
      physiological and biochemical responses of Paraisometrum mileense to extreme
      desiccation and found that it is a resurrection plant. We profiled the changes in
      lipid molecular species during dehydration and rehydration in P. mileense, and
      compared these with corresponding changes in the desiccation-sensitive plant
      Arabidopsis thaliana. One day of desiccation was lethal for A. thaliana but not
      for P. mileense. After desiccation and subsequent rewatering, A. thaliana showed
      dramatic lipid degradation accompanied by large increases in levels of
      phosphatidic acid (PA) and diacylglycerol (DAG). In contrast, desiccation and
      rewatering of P. mileense significantly decreased the level of
      monogalactosyldiacylglycerol and increased the unsaturation of membrane lipids,
      without changing the level of extraplastidic lipids. Lethal desiccation in P.
      mileense caused massive lipid degradation, whereas the PA content remained at a
      low level similar to that of fresh leaves. Neither damage nor repair processes,
      nor increases in PA, occurred during non-lethal desiccation in P. mileense. The
      activity of phospholipase D, the main source of PA, was much lower in P. mileense
      than in A. thaliana under control conditions, or after either dehydration or
      rehydration. It was demonstrated that low rates of phospholipase D-mediated PA
      formation in P. mileense might limit its ability to degrade lipids to PA, thereby
      maintaining membrane integrity following desiccation. 

PMID- 25068903
TI  - Data-driven lossy tube-load modeling of arterial tree: in-human study.
AB  - In this paper, we present and validate a data-driven method to lossy tube-load
      modeling of arterial tree in humans. In the proposed method, the lossy tube-load
      model is fitted to central aortic and peripheral blood pressure (BP) waves in the
      time domain. For this purpose, we employ a time-domain lossy tube-load model in
      which the wave propagation constant is formulated to two terms: one responsible
      for the alteration of wave amplitude and the other for the transport delay. Using
      the experimental BP data collected from 17 cardiac surgery patients, we showed
      that the time-domain lossy tube-load model is able to accurately represent the
      relation between central aortic versus upper-limb and lower-limb BP waves. In
      addition, the comparison of lossy versus lossless tube-load models revealed that
      (1) the former outperformed the latter in general with the root-mean-squared
      errors (RMSE) of 3.1 mm Hg versus 3.5 mm Hg, respectively (p-value < 0.05), and
      (2) the efficacy of the former over the latter was more clearly observed in case
      the normalized difference in the mean central aortic versus peripheral BP was
      large; when the difference was >5% of the underlying mean BP, lossy and lossless
      models showed the RMSE of 2.7 mm Hg and 3.7 mm Hg, respectively (p-value < 0.05).

PMID- 25068905
TI  - Graphene oxide based smart fluids.
AB  - Graphene oxide (GO), a graphene-related material containing oxygen-functional
      groups, has attracted considerable attention because of its strongly hydrophilic
      behavior and potential use in GO-hybrid composites. We put our focus on the
      fabrication and rheological characteristics of GO-based electrorheological and
      magnetorheological smart fluids under electric and magnetic fields, respectively
      in this Highlight. A brief perspective on the significant role of GO in tribology
      and the amphiphilic characteristics of Pickering emulsions are also included. 

PMID- 25068904
TI  - Polysome profiling shows the identity of human adipose-derived stromal/stem cells
      in detail and clearly distinguishes them from dermal fibroblasts.
AB  - Although fibroblasts and multipotent stromal/stem cells, including adipose
      derived stromal cells (ADSCs), have been extensively studied, they cannot be
      clearly distinguished from each other. We, therefore, investigated the cellular
      and molecular characteristics of ADSCs and fibroblasts. ADSCs and fibroblasts
      share several morphological similarities and surface markers, but were clearly
      found to be different types of cells. Contrary to previous reports, fibroblasts
      were not able to differentiate into adipocytes, osteoblasts, or chondrocytes.
      Polysome-bound mRNA profiling revealed that ~ 1,547 genes were differentially
      expressed (DE) in the two cell types; the genes were related to cell adhesion,
      the extracellular matrix, differentiation, and proliferation. These findings were
      confirmed by functional analyses showing that ADSCs had a greater adhesion
      capacity than fibroblasts; the proliferation rate of fibroblasts was also higher
      than that of ADSCs. Importantly, 185 DE genes were integral to the plasma
      membrane and, thus, candidate markers for ADSC isolation and manipulation. We
      also observed that an established marker of fibroblasts and ADSCs, CD105, was
      overexpressed in ADSCs at both mRNA and protein levels. CD105 expression seemed
      to be related to differentiation capacity, at least for adipogenesis. This study
      shows that ADSCs and fibroblasts are distinct cell types. These findings should
      be taken into account when using these two cell types in basic and therapeutic
      studies.

PMID- 25068907
TI  - Validation of direct and indirect measures of preference for sexualized violence.
AB  - Individuals differ in the extent to which they are interested in sexualized
      violence, as displayed in the frequent but not ubiquitous sexual interest in
      consensual acts of violent sexual role play and violent pornographic media in the
      normal population. The present research sought to develop and validate a multi
      method assessment battery to measure individual differences in the preference for
      sexualized violence. Three indirect measures (Implicit Association Test, Semantic
      Misattribution Procedure, Viewing Time) were combined in an online study with 107
      men and 103 women. Participants with and without an affiliation with
      sadomasochistic sexual interest groups were recruited on corresponding Internet
      platforms. Results revealed that all 3 indirect measures converged in predicting
      self-reported sexual interest in non-consensual sexuality. Specifically, for men
      all indirect measures were related to non-consensual sadistic sexual interest,
      whereas for women an association with masochistic sexual interest was found.
      Stimulus artefacts versus genuine gender differences are discussed as potential
      explanations of this dissociation. An outlook on the usability of the assessment
      battery in applied settings is delivered.

PMID- 25068906
TI  - Decision tree analyses of key patient characteristics in Middle Eastern/North
      African and Latin American men treated with long-acting and short-acting PDE5
      inhibitors for erectile dysfunction.
AB  - BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibitors have discontinuation rates
      as high as 60% in men with erectile dysfunction. Treatment satisfaction has been
      significantly associated with treatment continuation. Understanding key
      characteristics in terms of treatment preference, relationship, and lifestyle
      issues could provide direction on how to improve compliance with PDE5 inhibitor
      treatment globally. OBJECTIVE: The objective was to identify subgroups of
      interest in the pooled database of two observational studies conducted in Latin
      America (LA) and Middle East/North Africa (MENA) exploring patient
      characteristics and prescription of either a long- or short-acting PDE5 inhibitor
      at baseline. METHODS: Two identical prospective, non-interventional,
      observational, studies in MENA (N = 493) and LA (N = 511) treated men with an 'on
      demand' (pro re nata, PRN) PDE5 inhibitor (sildenafil, tadalafil, vardenafil, or
      lodenafil) during 6 months. In this post-hoc meta-analysis of two observational
      studies with equal design, pooled data were analyzed to determine patient
      characteristics and PDE5 inhibitor prescribed/used most likely to be associated
      with patient expectations, satisfaction, self-esteem, and patient-partner
      relationships. Decision tree analyses, with and without weighting, were used to
      identify and describe key features. RESULTS: In each analysis of patient
      expectations, patient-partner relationship, and self-esteem, we describe the two
      major subgroups at baseline for each decision tree. Analyses of patient
      expectations and sexual self-esteem revealed that patients prescribed long-acting
      PDE5 inhibitors (59%) highlighted the importance of treatment effect duration,
      second to partner satisfaction with treatment, while patients prescribed short
      acting PDE5 inhibitors (32%) placed less importance on treatment effect duration
      but considerable importance on treatment effect lasting until intercourse
      completion. Further insights regarding patients, partner relationship
      characteristics, and treatment expectations were identified. CONCLUSION: Our
      analyses have described key characteristics, such as self- and partner
      perceptions, sexual attitudes, and treatment expectations in relation to the
      patients' country and prescribed treatment, which might guide treatment decisions
      in MENA and LA men with ED.

PMID- 25068908
TI  - Confirmatory factor analysis, latent profile analysis, and factor mixture
      modeling of the syndromes of the Child Behavior Checklist and Teacher Report
      Form.
AB  - The current study used confirmatory factor analysis (CFA), latent profile
      analysis (LPA), and factor mixture modeling (FMM) to examine the co-occurrence of
      the childhood syndromes using the Child Behavior Checklist (CBCL) and Teacher
      Report Form (TRF). Parents and teachers completed the CBCL and TRF, respectively,
      for a clinic-referred sample of 720 children, ages 7-12 years. For the CBCL, the
      analyses indicated most support a 2-class 2-factor FMM, and for the TRF, there
      was most support for a 2-class 3-factor model. The classes were all syndromes at
      average levels and all syndromes at high levels. The findings indicate high
      syndrome co-occurrence. The implications of the findings for understanding
      syndrome co-occurrence in the CBCL and TRF, theories of syndrome co-occurrence,
      and the clinical use of the CBCL and TRF are discussed.

PMID- 25068909
TI  - The manifestation of depression in the context of urban poverty: a factor
      analysis of the Children's Depression Inventory in low-income urban youth.
AB  - The current study used confirmatory factor analysis (CFA) to compare the fit of 2
      factor structures for the Children's Depression Inventory (CDI) in an urban
      community sample of low-income youth. Results suggest that the 6-factor model
      developed by Craighead and colleagues (1998) was a strong fit to the pattern of
      symptoms reported by low-income urban youth and was a superior fit with these
      data than the original 5-factor model of the CDI (Kovacs, 1992). Additionally,
      results indicated that all 6 factors from the Craighead model contributed to the
      measurement of depression, including School Problems and Externalizing Problems
      especially for older adolescents. This pattern of findings may reflect distinct
      contextual influences of urban poverty on the manifestation and measurement of
      depression in youth.

PMID- 25068911
TI  - Optimists or optimistic? A taxometric study of optimism.
AB  - Although most researchers have assumed that optimism exists on a continuum, it is
      not uncommon for researchers to dichotomize their data into optimists and
      pessimists, thus treating optimism as a categorical or taxonic variable. To
      address the question of whether optimism is dimensional or taxonic, the authors
      performed a set of taxometric analyses on 3 indicators derived from measures of
      hope and optimism using data from 510 college students. The results provided
      consistent evidence that optimism is dimensional. Colloquially, people may speak
      of optimists and pessimists, but researchers should avoid dichotomizing this
      continuous variable.

PMID- 25068910
TI  - The clinical utility of the MMPI-2-RF Suicidal/Death Ideation Scale.
AB  - Suicide is a major public health concern, with over 100 individuals dying by
      suicide per day in the United States alone. Therefore, suicide risk assessment is
      an essential aspect of mental health care. The Minnesota Multiphasic Personality
      Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008-2011;
      Tellegen & Ben-Porath, 2008) has a Suicidal/Death Ideation (SUI) scale consisting
      of 5 items that describe recent suicidal ideation or behaviors. Although this
      scale has clear face validity, few studies have examined the clinical utility of
      this scale. The purpose of the current study was to examine associations between
      the SUI scale and other established measures of suicidal ideation and behavior,
      including the Depressive Symptom Inventory Suicidality Subscale (DSI-SS; Metalsky
      & Joiner, 1997), Beck Scale for Suicide Ideation (BSS; Beck & Steer, 1991; Beck,
      Steer, & Ranieri, 1988), self-report of lifetime suicide attempts, and clinician
      ratings of suicide risk. Participants were 998 therapy- and assessment-seeking
      outpatients. Analyses indicated that the SUI scale was positively associated with
      other self-reported measures of suicidal ideation and behavior. Significant
      differences in SUI scale scores also emerged among the clinician rating
      categories of suicide risk. The SUI scale was able to predict previous suicide
      attempts over and above age, gender, and other MMPI-2-RF scales related to
      depression. Finally, relative risk ratios for suicide attempts indicate increased
      risk of suicidality, with higher T scores on the SUI scale. Overall, findings
      suggest that the MMPI-2-RF SUI scale may be a useful tool for identifying
      individuals at risk for suicidal ideation and behavior in clinical settings.

PMID- 25068912
TI  - Self-consciousness and social anxiety in youth: the Revised Self-Consciousness
      Scales for Children.
AB  - Despite the established relationship between self-consciousness (SC) and anxiety
      and depression in adults, there is a paucity of research examining SC in children
      and adolescents. We therefore sought to examine the factor structure,
      reliability, and validity of scores for a revised version of the Self
      Consciousness Scales for Children, a measure of SC in youth. The Revised Self
      Consciousness Scale for Children (R-SCS-C) was examined in 2 studies using a
      community sample of children and adolescents. In the 1st study, 1,207 youth (685
      girls) ages 7 to 18 completed the R-SCS-C as well as measures of imaginary
      audience, anxiety, depression, and positive and negative affect. Results of an
      exploratory factor analysis of the R-SCS-C conducted on a randomly selected
      subsample (n = 603) supported a 3-factor solution, including the subscales of
      Public Self-Consciousness, Private Self-Consciousness, and Social Anxiety. A
      subsequent confirmatory factor analysis (CFA) conducted on the remaining half of
      the sample (n = 604) revealed that this model fit the data well. Additionally,
      subsequent multigroup CFAs by gender and age demonstrated good model fit across
      both gender and younger (ages 7 to 12 years) and older (ages 13 to 18 years)
      cohorts. In the 2nd study, 245 youth completed the R-SCS-C twice, approximately 2
      weeks apart. The R-SCS-C scores in these samples demonstrated acceptable internal
      consistency, convergent and divergent validity, and test-retest reliability.
      Implications of these findings and directions for future research are discussed.

PMID- 25068913
TI  - Factor mixture modeling of anxiety sensitivity: a three-class structure.
AB  - Anxiety sensitivity (AS) is a multidimensional construct composed of several
      lower order factors and has been implicated in the development and maintenance of
      anxiety and depression symptoms and disorders. Recently, it has been suggested
      that AS is a dimensional-categorical construct, reflecting classes of individuals
      with different levels of and relations between AS factors. Factor mixture
      modeling was applied to examine the latent structure of AS in a sample of 1,151
      college students (M age = 18.88, SD = 1.91). Results indicated that the best
      fitting model comprised three classes consisting of individuals with normative AS
      (n = 953), moderate AS (n = 124), and high AS (n = 74). Relations among the
      factors appeared to be different across groups, with the highest relations found
      in the normative AS class and the lowest relations found in the high AS class.
      There were significant differences in mean levels of anxiety and depression
      symptoms across classes, with the exception of social anxiety disorder symptoms.
      This study was the first to find and provide support for a third AS class.
      Implications for research and clinical utility are discussed, including the
      benefit of developing cut scores for AS classes based on this and similar
      studies.

PMID- 25068914
TI  - Mokken scales for testing both pre- and postintervention: an analysis of the
      Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) before and
      after counseling.
AB  - Mokken scaling is increasingly being applied to assessing the extent to which
      clinical scales possess clinically useful properties, especially invariant item
      ordering (IIO). These scales are often used to track progress in symptoms over
      time to evaluate the success of an intervention. Such interventions are designed
      to affect psychopathological trait levels overall but may in some cases act
      disproportionately on some symptoms over others. As a result, there is no
      guarantee that the item orderings of a clinical scale will be preserved between
      the point at which individuals begin treatment and the point at which they can be
      considered recovered. In these situations, many of the potential benefits of IIO
      are undermined because an IIO identified at either time point will not be
      informative about changes in symptoms over time. In this study, we aimed to
      assess the extent to which the Clinical Outcomes in Routine Evaluation-Outcome
      Measure (CORE-OM) retained the same item orderings in a sample of individuals
      when initially presenting for counseling treatment and when discharged. From the
      34 items of the CORE-OM we found a subset of 10 items exhibiting monotonicity,
      invariant item ordering, and highly similar item orderings when measured at both
      time points.

PMID- 25068915
TI  - YouTube as a potential learning tool to help distinguish tonic-clonic seizures
      from nonepileptic attacks.
AB  - Medical students are increasingly turning to the website YouTube as a learning
      resource. This study set out to determine whether the videos on YouTube
      accurately depict the type of seizures that a medical student may search for. Two
      consultant epileptologists independently assessed the top YouTube videos returned
      following searches for eight terms relating to different categories of seizures.
      The videos were rated for their technical quality, concordance of diagnosis with
      an epileptologist-assigned diagnosis, and efficacy as a learning tool for medical
      education. Of the 200 videos assessed, 106 (63%) met the inclusion criteria for
      further analysis. Technical quality was generally good and only interfered with
      the diagnostic process in 8.5% of the videos. Of the included videos, 40.6-46.2%
      were judged to depict the purported diagnosis with moderate agreement between
      raters (75% agreement, kappa=0.50). Of the videos returned after searching "tonic
      clonic seizure", 28.6-35.7% were judged to show nonepileptic seizures with almost
      perfect interrater agreement (92.9% agreement, kappa=0.84). Of the videos
      returned following the search "pseudoseizure", 77.8-88.9% of videos were judged
      to show nonepileptic seizures with substantial agreement (88.9% agreement,
      kappa=0.61). Across all search terms, 19.8-33% of videos were judged as
      potentially useful as a learning resource, with fair agreement between raters
      (75.5% agreement, kappa=0.38). These findings suggest that the majority of videos
      on YouTube claiming to show specific seizure subtypes are inaccurate, and YouTube
      should not be recommended as a learning tool for students. However, a small group
      of videos provides excellent demonstrations of tonic-clonic and nonepileptic
      seizures, which could be used by an expert teacher to demonstrate the difference
      between epileptic and nonepileptic seizures. 

PMID- 25068916
TI  - Molecular umbrella-amphotericin B conjugates.
AB  - A tetrawalled and an octawalled molecular umbrella conjugate of amphotericin B
      (AmB) have been synthesized. Both conjugates exhibit high water solubility, a low
      tendency to aggregate, negligible hemolytic activity at 100 MUM, and an ability
      to release a derivative of AmB under reducing conditions that exhibits high
      antifungal activity. Whereas the larger, octawalled conjugate shows slight
      adsorption to liposomal membranes and an ability to cross them by passive
      transport, the tetrawalled analogue shows significant adsorption and much lower
      bilayer transport activity. The potential of molecular umbrella-AmB conjugates as
      therapeutic agents is briefly discussed. 

PMID- 25068917
TI  - Reinfection after successful eradication of Helicobacter pylori in three
      different populations in Alaska.
AB  - We performed a study to determine rates of reinfection in three groups followed
      for 2 years after successful treatment: American Indian/Alaska Native (AI/AN)
      persons living in urban (group 1) and rural (group 2) communities, and urban
      Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori
      infection based on a positive urea breath test (13C-UBT). After successful
      treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6,
      12 and 24 months. At each visit, participants were asked about medication use,
      illnesses and risk factors for reinfection. We followed 229 persons for 2 years
      or until they became reinfected. H. pylori reinfection occurred in 36 persons;
      cumulative reinfection rates were 14.5%, 22.1%, and 12.0% for groups 1, 2, and 3,
      respectively. Study participants who became reinfected were more likely to have
      peptic ulcer disease (P = 0.02), low education level (P = 0.04), or have a higher
      proportion of household members infected with H. pylori compared to participants
      who did not become reinfected (P = 0.03). Among all three groups, reinfection
      occurred at rates higher than those reported for other US populations (<5% at 2
      years); rural AI/AN individuals appear to be at highest risk for reinfection.

PMID- 25068918
TI  - Fluorescence properties reinforced by proton transfer in the salt 2,6
      diaminopyridinium dihydrogen phosphate.
AB  - Luminescent materials have many interesting applications, but it remains
      difficult to control the luminescence of organic materials and in particular to
      retain the same luminescence in solution and in the solid state, a property of
      interest for various imaging applications. In the present work, the fluorescent
      properties of the salt of 2,6-diaminopyridinium with dihydrogen phosphate have
      been explored. As a result of proton transfer from phosphoric acid to the
      pyridine nitrogen and the stabilizing effect of the two primary amines at the
      positions ortho to the pyridine nitrogen, the band gap between the HOMO and the
      LUMO is considerably diminished in comparison with that in 2,6-diaminopyridine.
      This is confirmed by a red shift in its absorption spectrum. Because protonation
      is retained in aqueous solution, the dissolved 2,6-diaminopyridinium dihydrogen
      phosphate salt retains a similar fluorescent spectrum as in the solid state. The
      crystals have been studied by single-crystal X-ray diffraction; FTIR, Raman, UV
      vis-NIR, and luminescence spectroscopy; HOMO-LUMO calculations using DFT; and
      thermal analysis. The compound provides an example of a supramolecular motif that
      controls the crystal structure and the luminescence properties. In addition, the
      crystal exhibits negligible thermal expansion over a temperature interval of 150 
      degrees C. In short, 2,6-diaminopyridinium dihydrogen phosphate is an interesting
      compound for the design of luminescent devices. 

PMID- 25068920
TI  - Effects of microwave heating on the migration of substances from melamine
      formaldehyde tableware.
AB  - Melamine formaldehyde (MF) tableware, after undergoing repeated heating in a
      microwave oven for 1, 2, 3 or 5 min, was tested for migration into 3% (w/v)
      acetic acid, a food simulant. Overall migration (OM) consistently increased with
      an increasing number of heating/washing cycles, while formaldehyde was found at
      low concentrations or was not detectable. Unexpectedly, the 1-min series caused
      the most rapid increase in OM; the European Union regulatory limit of 10 mg dm(
      2) was exceeded after 25 cycles. The number of cycles required to reach the OM
      limit rose to 29 and 67 for the 2- and 3-min series, respectively. Only 37 cycles
      were needed in the case of the 5-min series; however, the cumulative exposure
      time to microwave irradiation was relatively close to that of the 3-min series.
      These findings indicate that microwave heating affects the migration of MF in a
      significantly different manner as compared with conventional heating reported in
      previous studies. Fourier transform infrared spectroscopy (FTIR) spectra of MF
      after completing the microwave heating series show that the plastic was not fully
      cured, as evidenced by the absence of methylene linkages. The majority of
      migrants obtained from OM tests consisted of low molecular weight methylol
      melamine derivatives. The results indicate that microwave heating allowed
      demethylolation, addition and condensation reactions to occur, which was not the
      case when using conventional heating. This study demonstrates that microwave
      heating for 1-2 min in a repeated manner is of high concern in terms of consumer
      health. It was found that the service terms of melamine ware under microwave
      heating were drastically reduced, by more than 10-fold, as compared with the
      service terms under conventional heating. Hence, it is strongly recommended that
      manufacturers of MF articles provide instructions for use, e.g. "Do not use in
      microwave", which should be clearly visible to consumers and not easily
      detachable.

PMID- 25068919
TI  - Living biointerfaces based on non-pathogenic bacteria to direct cell
      differentiation.
AB  - Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the
      FNIII(7-10) fibronectin fragment as a protein membrane have been used to create a
      living biointerface between synthetic materials and mammalian cells. This FNIII(7
      10) fragment comprises the RGD and PHSRN sequences of fibronectin to bind
      alpha5beta1 integrins and triggers signalling for cell adhesion, spreading and
      differentiation. We used L. lactis strain to colonize material surfaces and
      produce stable biofilms presenting the FNIII(7-10) fragment readily available to
      cells. Biofilm density is easily tunable and remains stable for several days.
      Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and
      form differentiated myotubes, a process triggered by the FNIII(7-10) fragment.
      This biointerface based on living bacteria can be further modified to express any
      desired biochemical signal, establishing a new paradigm in biomaterial surface
      functionalisation for biomedical applications.

PMID- 25068921
TI  - Dynamic contrast-enhanced, extremity-dedicated MRI identifies synovitis changes
      in the follow-up of rheumatoid arthritis patients treated with rituximab.
AB  - OBJECTIVES: The aim of this study is to assess prospectively the effect of
      rituximab (RTX) on MRI features of wrist joint disease in patients affected by
      rheumatoid arthritis (RA). METHODS: Ten patients (6F/4M, mean age 52.9+/-15.5
      years) diagnosed with IgM rheumatoid factor, anti-CCP positive, RA according to
      the 1987 ACR criteria were treated with a single course of RTX (2 infusions of
      1000 mg, 15 days apart). MRI of the dominant hand was performed with a 0.2T
      extremity-dedicated machine using pre and post contrast T1 weighted SE, turbo 3D,
      and STIR sequences at baseline, and after 4 and 24 weeks. MRI was analysed using
      the OMERACT-RAMRIS score and the dynamic contrast-enhanced (DCE-MRI) technique
      for wrist synovitis, which calculates the enhancement ratio as both rate of early
      enhancement (REE) and relative enhancement (RE). The corresponding ME and IRE
      parameters were calculated also through a computer-aided semi-automated method on
      the mean of three MRI slices and on a small ROI positioned in the area of maximum
      enhancement. RESULTS: DAS significantly decreased during the study period (ANOVA
      for repeated measures, p=0.005). The RAMRIS score did not change along the study,
      whereas the dynamic MRI values RE, IRE and ME on the small ROI significantly
      decreased. RE, but not the RAMRIS synovitis score, significantly correlated with
      DAS at baseline, 1 and 6 months (p=0.005, 0.04, and 0.0007, respectively).
      CONCLUSIONS: RTX confirmed good clinical efficacy, which was paralleled by a
      significant decrease in dynamic MRI results for wrist synovitis. On the contrary,
      the traditional RAMRIS measures did not change.

PMID- 25068922
TI  - A molecular "screw-clamp": accelerating click reactions in miniemulsions.
AB  - The interface as a "screw clamp": the copper-free 1,3-dipolar azide-alkyne
      cycloaddition at the interface of nanodroplets in miniemulsions was studied in
      detail by NMR spectroscopic methods. The reaction at the oil-water interface
      proved to exhibit higher rate constants, increased molecular weights and high
      regioregularity compared to the reaction in solution. 

PMID- 25068923
TI  - Morphological behaviour and metabolic capacity of cryopreserved human primary
      hepatocytes cultivated in a perfused multiwell device.
AB  - 1. The quantitative prediction of the pharmacokinetic parameters of a drug from
      data obtained using human in vitro systems remains a significant challenge i.e.
      prediction of metabolic clearance in humans and estimation of the relative
      contribution of enzymes involved in the clearance. This has become particularly
      problematic for low turnover compounds. 2. Having human hepatocytes with stable
      cellular function over several days that adequately mimic the complexity of the
      physiological environment would be a major advance. Thus, we evaluated human
      hepatocytes, maintained in culture during 7 days in the microfluidic LiverChipTM
      system, in terms of morphological appearance, relative mRNA expression of phase I
      and II enzymes and transporters as a function of time, and metabolic capacity
      using probe substrates. 3. The results showed that mRNA levels of the major genes
      for enzymes involved in drug metabolism were well-maintained over a 7-day period
      of culture. Furthermore, after 4 days of culture, in the LiverchipTM device,
      human hepatocytes exhibited higher or similar CYPs activities compared to 1 day
      of culture in 2D-static conditions. 4. The functional data were supported by
      light/electron microscopies and immunohistochemistry showing viable tissue
      structure and well-differentiated human hepatocytes: presence of cell junctions,
      glycogen storage, and bile canaliculi.

PMID- 25068924
TI  - Cancer cell growth inhibitory effect of bee venom via increase of death receptor
      3 expression and inactivation of NF-kappa B in NSCLC cells.
AB  - Our previous findings have demonstrated that bee venom (BV) has anti-cancer
      activity in several cancer cells. However, the effects of BV on lung cancer cell
      growth have not been reported. Cell viability was determined with trypan blue
      uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related
      protein expression was determined with Western blotting. An EMSA was used for
      nuclear factor kappaB (NF-kappaB) activity assay. BV (1-5 MUg/mL) inhibited
      growth of lung cancer cells by induction of apoptosis in a dose dependent manner
      in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell
      death, expression of DR3 and DR6 was significantly increased. However, deletion
      of DRs by small interfering RNA significantly reversed BV induced cell growth
      inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax) was
      concomitantly increased, but the NF-kappaB activity and expression of Bcl-2 were
      inhibited. A combination treatment of tumor necrosis factor (TNF)-like weak
      inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and
      cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer
      cell growth with further down regulation of NF-kappaB activity. These results
      show that BV induces apoptotic cell death in lung cancer cells through the
      enhancement of DR3 expression and inhibition of NF-kappaB pathway. 

PMID- 25068925
TI  - Thuringiensin: a thermostable secondary metabolite from Bacillus thuringiensis
      with insecticidal activity against a wide range of insects.
AB  - Thuringiensin (Thu), also known as beta-exotoxin, is a thermostable secondary
      metabolite secreted by Bacillus thuringiensis. It has insecticidal activity
      against a wide range of insects, including species belonging to the orders
      Diptera, Coleoptera, Lepidoptera, Hymenoptera, Orthoptera, and Isoptera, and
      several nematode species. The chemical formula of Thu is C22H32O19N5P, and it is
      composed of adenosine, glucose, phosphoric acid, and gluconic diacid. In contrast
      to the more frequently studied insecticidal crystal protein, Thu is not a protein
      but a small molecule oligosaccharide. In this review, a detailed and updated
      description of the characteristics, structure, insecticidal mechanism, separation
      and purification technology, and genetic determinants of Thu is provided. 

PMID- 25068926
TI  - Preschool predictors of mathematics in first grade children with autism spectrum
      disorder.
AB  - Up till now, research evidence on the mathematical abilities of children with
      autism spectrum disorder (ASD) has been scarce and provided mixed results. The
      current study examined the predictive value of five early numerical competencies
      for four domains of mathematics in first grade. Thirty-three high-functioning
      children with ASD were followed up from preschool to first grade and compared
      with 54 typically developing children, as well as with normed samples in first
      grade. Five early numerical competencies were tested in preschool (5-6 years):
      verbal subitizing, counting, magnitude comparison, estimation, and arithmetic
      operations. Four domains of mathematics were used as outcome variables in first
      grade (6-7 years): procedural calculation, number fact retrieval, word/language
      problems, and time-related competences. Children with ASD showed similar early
      numerical competencies at preschool age as typically developing children.
      Moreover, they scored average on number fact retrieval and time-related
      competences and higher on procedural calculation and word/language problems
      compared to the normed population in first grade. When predicting first grade
      mathematics performance in children with ASD, both verbal subitizing and counting
      seemed to be important to evaluate at preschool age. Verbal subitizing had a
      higher predictive value in children with ASD than in typically developing
      children. Whereas verbal subitizing was predictive for procedural calculation,
      number fact retrieval, and word/language problems, counting was predictive for
      procedural calculation and, to a lesser extent, number fact retrieval.
      Implications and directions for future research are discussed. 

PMID- 25068928
TI  - Animal experimentation: transparency and openness mean little, unless accompanied
      by honesty and accountability.

PMID- 25068927
TI  - Reaction of an iron(IV) nitrido complex with cyclohexadienes: cycloaddition and
      hydrogen-atom abstraction.
AB  - The iron(IV) nitrido complex PhB(MesIm)3Fe=N reacts with 1,3-cyclohexadiene to
      yield the iron(II) pyrrolide complex PhB(MesIm)3Fe(eta(5)-C4H4N) in high yield.
      The mechanism of product formation is proposed to involve sequential [4 + 1]
      cycloaddition and retro Diels-Alder reactions. Surprisingly, reaction with 1,4
      cyclohexadiene yields the same iron-containing product, albeit in substantially
      lower yield. The proposed reaction mechanism, supported by electronic structure
      calculations, involves hydrogen-atom abstraction from 1,4-cyclohexadiene to
      provide the cyclohexadienyl radical. This radical is an intermediate in substrate
      isomerization to 1,3-cyclohexadiene, leading to formation of the pyrrolide
      product. 

PMID- 25068929
TI  - Perceived barriers to the adoption of alternatives to laboratory animal use for
      rabies diagnosis.
AB  - The use of laboratory animals is still common practice, but some uses can be
      replaced by alternative methods, such as Virus Isolation in Cell Culture (VICC)
      instead of the Mouse Inoculation Test (MIT) for rabies diagnosis. The objective
      of this work was to describe current rabies diagnosis methods in Brazil and other
      countries, and the constraints associated with replacing this use of mice with
      alternative methods. Nine out of 12 Brazilian and 14 out of 43 non-Brazilian
      respondents reported that they currently used the MIT. Respondents in countries
      other than Brazil, male respondents, and those already employing in vitro methods
      for rabies diagnosis, expressed higher levels of support for the use of
      alternatives. The most frequently reported constraints associated with the use of
      alternatives were lack of laboratory facilities, equipment and materials (cited
      17 times by respondents), and lack of financial resources (cited 15 times). The
      results indicate that many laboratories continue to use mice for rabies
      diagnosis. The proportion of laboratories that use mice appears to be especially
      high in Brazil, despite animal protection laws and technical guidelines that
      favour the use of alternatives. The barriers to the adoption of alternative
      methods identified in the current study provide a basis for facilitating changes
      in Brazil and elsewhere. 

PMID- 25068930
TI  - An analysis of the use of animal models in predicting human toxicology and drug
      safety.
AB  - Animal use continues to be central to preclinical drug development, in spite of a
      lack of its demonstrable validity. The current nadir of new drug approvals and
      the drying-up of pipelines may be a direct consequence of this. To estimate the
      evidential weight given by animal data to the probability that a new drug may be
      toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data
      set of 2,366 drugs, for which both animal and human data are available, including
      tissue-level effects and MedDRA Level 1-4 biomedical observations. This was done
      for three preclinical species (rat, mouse and rabbit), to augment our previously
      published analysis of canine data. In common with our dog analysis, the resulting
      LRs show: a) that the absence of toxicity in the animal provides little or
      virtually no evidential weight that adverse drug reactions (ADRs) will also be
      absent in humans; and b) that, while the presence of toxicity in these species
      can add considerable evidential weight for human risk, the LRs are extremely
      inconsistent, varying by over two orders of magnitude for different classes of
      compounds and their effects. Therefore, our results for these additional
      preclinical species have important implications for their use in predicting human
      toxicity, and suggest that alternative methods are urgently required. 

PMID- 25068931
TI  - Development of a training model for small animal thoracocentesis and chest tube
      thoracostomy.
AB  - Training veterinary students to perform emergency procedures, such as
      thoracocentesis and chest tube thoracostomy, poses challenges in terms of
      providing adequate hands-on experience without compromising animal welfare. A
      small animal thoracocentesis and chest tube thoracostomy model has been
      developed, that allows repetitive practice in a safe, standardised environment.
      The model has been incorporated into a clinical skills laboratory, where students
      work through computerised case studies in small groups, performing
      thoracocentesis or chest tube thoracostomy where indicated during the case.
      Student feedback indicated a high degree of satisfaction with the model and the
      laboratory experience, high perceived value of the case studies in improving
      learning, and increased confidence to perform the procedures under supervision.
      This model can replace the use of live animals while students are practising
      these procedures, improving their technique, and learning the appropriate
      safeguards used to prevent injuries such as pulmonary trauma. 

PMID- 25068932
TI  - A severe case of fraudulent blending of fetal bovine serum strengthens the case
      for serum-free cell and tissue culture applications.

PMID- 25068933
TI  - Our guiding principles.

PMID- 25068934
TI  - Human bioengineered artery models for in vitro atherosclerosis research: fact or
      fiction?

PMID- 25068935
TI  - FRAME's online alternatives timeline goes live.

PMID- 25068936
TI  - 11. The analysis of direct inhumanity.

PMID- 25068937
TI  - Emotional intelligence in the operating room: analysis from the Boston Marathon
      bombing.
AB  - INTRODUCTION: The Boston Marathon terrorist bombing that occurred on April 15,
      2013 illustrates the importance of a cohesive, efficient management for the
      operating room and perioperative services. Conceptually, emotional intelligence
      (EI) is a form of social intelligence used by individuals in leadership positions
      to monitor the feelings and emotions of their team while implementing a strategic
      plan. OBJECTIVE: To describe the experience of caring for victims of the bombing
      at a large tertiary care center and provide examples demonstrating the importance
      of EI and its role in the management of patient flow and overall care. METHODS: A
      retrospective review of trauma data was performed. Data regarding patient flow,
      treatment types, treatment times, and outcomes were gathered from the hospital's
      electronic tracking system and subsequently analyzed. Analyses were performed to
      aggregate the data, identify trends, and describe the medical care. RESULTS:
      Immediately following the bombing, a total of 35 patients were brought to the
      emergency department (ED) with injuries requiring immediate medical attention. 10
      of these patients went directly to the operating room on arrival to the hospital.
      The first victim was in an operating room within 21 minutes after arrival to the
      ED. CONCLUSION: The application of EI in managerial decisions helped to ensure
      smooth transitions for victims throughout all stages of their perioperative care.
      EI provided the fundamental groundwork that allowed the operating room manager
      and nurse leaders to establish the calm and coordinated leadership that
      facilitated patient care and teamwork.

PMID- 25068938
TI  - An intervention for enhancing public health crisis response willingness among
      local health department workers: a qualitative programmatic analysis.
AB  - OBJECTIVES: This study evaluated the impact of a novel multimethod curricular
      intervention using a train-the-trainer model: the Public Health Infrastructure
      Training (PHIT). PHIT was designed to 1) modify perceptions of self-efficacy,
      response efficacy, and threat related to specific hazards and 2) improve the
      willingness of local health department (LHD) workers to report to duty when
      called upon. METHODS: Between June 2009 and October 2010, eight clusters of US
      LHDs (n = 49) received PHIT. Two rounds of focus groups at each intervention site
      were used to evaluate PHIT. The first round of focus groups included separate
      sessions for trainers and trainees, 3 weeks after PHIT. The second round of focus
      groups combined trainers and trainees in a single group at each site 6 months
      following PHIT. During the second focus group round, participants were asked to
      self-assess their preparedness before and after PHIT implementation. SETTING:
      Focus groups were conducted at eight geographically representative clusters of
      LHDs. PARTICIPANTS: Focus group participants included PHIT trainers and PHIT
      trainees within each LHD cluster. MAIN OUTCOME MEASURE(S): Focus groups were used
      to assess attitudes toward the curricular intervention and modifications of
      willingness to respond (WTR) to an emergency; self-efficacy; and response
      efficacy. RESULTS: Participants reported that despite challenges in administering
      the training, PHIT was well designed and appropriate for multiple management
      levels and disciplines. Positive mean changes were observed for all nine self
      rated preparedness factors (p < 0.001). The findings show PHIT's benefit in
      improving self-efficacy and WTR among participants. CONCLUSIONS: The PHIT has the
      potential to enhance emergency response willingness and related self-efficacy
      among LHD workers.

PMID- 25068939
TI  - Academic-community partnerships for sustainable preparedness and response
      systems.
AB  - Academic institutions possess tremendous resources that could be important for
      community disaster response and preparedness activities. In-depth exploration of
      the role of academic institutions in community disaster response has elicited
      information about particular academic resources leveraged for and essential to
      community preparedness and response; factors that contribute to the decision
      making process for partner engagement; and facilitators of and barriers to
      sustainable collaborations from the perspectives of academic institutions, public
      health and emergency management agencies, and national association and agency
      leaders. The Academic-Community Partnership Project of the Emory University
      Preparedness and Emergency Response Research Center in collaboration with the
      Association of Schools of Public Health convened an invitational summit which
      included leadership from the National Association of County and City Health
      Officials, Association of State and Territorial Health Officials, Directors of
      Public Health Preparedness, Department of Health and Human Services Office of the
      Assistant Secretary for Preparedness and Response, CDC Office of Public Health
      Preparedness and Response, Association of Schools of Public Health, Association
      of American Medical Colleges, Association of Academic Health Centers, American
      Association of Colleges of Nursing, Council of State and Territorial
      Epidemiologists, and American Association of Poison Control Centers. From this
      convention, emerged recommendations for building and sustaining academic-public
      health-community collaborations for preparedness locally and regionally. 

PMID- 25068940
TI  - Mental health outcomes among vulnerable residents after Hurricane Sandy:
      implications for disaster research and planning.
AB  - OBJECTIVE: To evaluate mental health outcomes among New Jersey shore residents
      with health impairments and disabilities after Hurricane Sandy. DESIGN AND
      SETTING: Six months following Hurricane Sandy, a cross-sectional survey of 200
      adults residing in beach communities directly exposed to the storm located in
      Monmouth County, NJ, was conducted. MAIN OUTCOME MEASURES: Post-traumatic stress
      disorder (PTSD), depression, mental health service use, and medication use.
      RESULTS: The average age of residents surveyed was 59 years (SD = 13.7) and 52.5
      percent (95% CI = 45.5-59.4) reported recent hospitalizations, physical
      limitations, fair to poor health status, multiple chronic health conditions, or
      physical disabilities. A total of 14.5 percent (95% CI = 10.2-20.1) of residents
      screened positive for PTSD and 6.0 percent (95% CI = 3.1-10.2) met criteria for
      depression 6 months after Sandy. In addition, 20.5 percent (95% CI = 15.4-26.7)
      sought some type of professional counseling after Sandy and 30.5 percent (95% CI
      = 24.5-37.3) experienced PTSD symptoms, depression, sought professional mental
      health support, or used psychotropic medications. In multivariate analyses, the
      best predictors of mental health and service use were having sleep problems,
      suicidal thoughts, moderate or severe pain, and having high exposure hurricane
      related events. Analyses also suggested that noncollege graduates were more
      likely to receive mental health services (OR = 3.10, p = 0.009), while women were
      less likely to have depression (OR = 0.12, p = 0.038). CONCLUSION: Having
      physical impairments and health conditions were not directly related to adverse
      mental health outcomes following Sandy, but having sleep problems, pain, or
      suicidal thoughts were. Further research is needed to assess the health status of
      community residents with serious health impairments over time following
      disasters.

PMID- 25068941
TI  - Embedding a surgeon in a civilian tactical team reduces resource utilization and
      is cost effective.
AB  - OBJECTIVE: This study evaluates whether embedding a surgeon in a civilian
      tactical team (Special Weapons and Tactics [SWAT]) reduces resource utilization
      during training or deployment and is cost effective. DESIGN: Prospective, non
      interventional. PARTICIPANTS: All tactical police surgeon (TPS) activities (2011
      2013) were prospectively captured via databases (Bento and Excel) including days
      of activity, training and deployment care (team members, suspects, and
      bystanders), academic activity, costs incurred for equipment and training, as
      well as costs avoided by onscene care and evaluation. Umbrella activities related
      to non-SWAT care and system referral were recorded. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Resource utilization, costs, and outcomes derived from
      embedding a surgeon in a civilian tactical team. RESULTS: There were 24 days of
      training and two deployments; 3 days of staff coverage were required. Team
      members required 18 distinct care episodes; no suspects required care. Bystander
      care was required twice; both were treated on-scene avoiding transport and
      hospital care. Non-SWAT care occurred 36 times. No complications occurred except
      for one urinary track infection. Comorbid medical condition evaluation and
      management advice in non-SWAT officers, spouses, or significant others occurred
      24 times. New health system referral occurred 26 times. Total TPS equipment
      charges ($6,000) were offset by reduced scene transport ($3,000) and hospital
      care ($4,000), as well as reduced team member hospital care ($9,000) leading to a
      net Police Department (PD) charge surplus of (+)$9,000. New referral initial
      evaluation ($10,400) and operative charges ($30,800) were balanced against lost
      work ($6,500/d * 3d = $21,500) for a net health system charge surplus of
      (+)$19,700. One international presentation, three local presentations, and four
      peer-reviewed and five lay press publications accrued from these activities.
      CONCLUSIONS: A TPS reduces scene and Emergency Department resource utilization
      and increases new patient health system entry. Establishing a TPS is cost
      effective for a PD and an academic health system and supports academic
      productivity but may not be supportable without nonclinical days.

PMID- 25068942
TI  - Medical support for law enforcement-extended operations incidents.
AB  - OBJECTIVE: As the complexity and frequency of law enforcement-extended operations
      incidents continue to increase, so do the opportunities for adverse health and
      well-being impacts on the responding officers. These types of clinical encounters
      have not been well characterized nor have the medical response strategies which
      have been developed to effectively manage these encounters been well described.
      The purpose of this article is to provide a descriptive epidemiology of the
      clinical encounters reported during extended law enforcement operations, as well
      as to describe a best practices approach for their effective management. DESIGN:
      This study retrospectively examined the clinical encounters of the Maryland State
      Police (MSP) Tactical Medical Unit (TMU) during law enforcement extended
      operations incidents lasting 8 or more hours. In addition, a qualitative analysis
      was performed on clinical data collected by federal law enforcement agencies
      during their extended operations. RESULTS: Forty-four percent of missions
      (455/1,047) supported by the MSP TMU lasted 8 or more hours. Twenty-six percent
      of these missions (117/455) resulted in at least one patient encounter. Nineteen
      percent of patient chief complaints (45/238) were related to heat illness/
      dehydration. Fifteen percent of encounters (36/238) were for musculoskeletal
      injury/pain. Eight percent of patients (19/238) had nonspecific sick call (minor
      illness) complaints. The next most common occurring complaints were cold-related
      injuries, headache, sinus congestion, and wound/laceration, each of which
      accounted for 7 percent of patients (16/238), respectively. Analysis of federal
      law enforcement agencies' response to such events yielded similar clinical
      encounters. CONCLUSIONS: A wide range of health problems are reported by extended
      law enforcement operations personnel. Timely and effective treatment of these
      problems can help ensure that the broader operations mission is not compromised.
      An appropriate operational strategy for managing health complaints reported
      during extended operations involves the deployment of a well-trained medical
      support team using the core concepts of tactical emergency medical support.

PMID- 25068944
TI  - Use of a fiber optic camera to perform a trauma assessment during a confined
      space rescue.
AB  - OBJECTIVE: Accurate medical evaluation of victims injured during confined space
      rescues poses significant operational, medical, and logistical challenges for
      medical providers of all disciplines and experience levels. The Federal Emergency
      Management Agency (FEMA) teaches rescuers to begin their assessment as soon as
      verbal contact is obtained with the victim. While a significant amount of
      information can be obtained by talking to the victim, an accurate assessment of
      the victim's condition is often limited or impossible. Many professional rescue
      agencies currently use cameras to locate a victim's position or visualize
      obstacles that prevent the successful extraction of casualties. However, there is
      no published literature describing the use of a camera to complete a medical
      evaluation. RESULTS: The authors describe their use of a fiber optic camera to
      complete a limited but accurate primary and secondary trauma evaluation of a
      patient trapped inside an 18 in water pipe for a prolonged period of time. The
      providers' assessment provided critical information to the rescue team and
      assisted in the planning and eventual extrication of the patient from the
      confined space. Moreover, there was very little variation between the findings
      obtained during the assessment at the scene and the assessment in the receiving
      facility's trauma bay. CONCLUSION: When evaluating a trauma patient, there is no
      substitution for visual inspection and physical diagnosis. The use of a fiber
      optic camera can assist rescuers and medical providers in obtaining the
      information they desire, and enable the completion of an accurate patient
      assessment. The camera may also provide psychological reassurance and ease
      anxiety, as well as generate prehospital images that can be transmitted to the
      receiving facility for use in preparation of the casualty. Emergency medical
      service providers, urban search & rescue teams, fire departments, and other
      professional rescuers should be trained on the use and limitations of fiber optic
      cameras during confined space rescues. Furthermore, regulatory agencies such as
      FEMA should consider integrating the use of fiber optic camera and audiovisual
      devices into the current training courses offered to professional rescuers.

PMID- 25068945
TI  - Synthesis of polyfluoroalkyl aza-polycyclic aromatic hydrocarbons enabled by
      addition of perfluoroalkyl radicals onto vinyl azides.
AB  - Radical perfluoroalkylation of alpha-(biaryl-2-yl)vinyl azides is capable of
      supplying polyfluoroalkyl aza-polycyclic aromatic hydrocarbons (aza-PAHs).
      Commercially available Me3SiRf (Rf = CF3, C2F5, and C3F7) are employed as the
      sources of perfluoroalkyl radicals upon oxidation with PhI(OAc)2. The addition of
      perfluoroalkyl radicals to biarylvinyl azides generates the corresponding iminyl
      radicals, which subsequently cyclize with the intramolecular arene moiety,
      furnishing aza-PAH skeletons having polyfluoroalkyl (RfCH2) function. 

PMID- 25068943
TI  - A review of the literature on the validity of mass casualty triage systems with a
      focus on chemical exposures.
AB  - INTRODUCTION: Mass casualty incidents (MCIs) include natural (eg, earthquake) or
      human (eg, terrorism or technical) events. They produce an imbalance between
      medical needs and resources necessitating the use of triage strategies. Triage of
      casualties must be performed accurately and efficiently if providers are to do
      the greatest good for the greatest number. There is limited research on the
      validation of triage system efficacy in determining the priority of care for
      victims of MCI, particularly those involving chemicals. OBJECTIVE: To review the
      literature on the validation of current triage systems to assign on-site
      treatment status codes to victims of mass casualties, particularly those
      involving chemicals, using actual patient outcomes. METHODS: The focus of this
      article is a systematic review of the literature to describe the influences of
      MCIs, particularly those involving chemicals, on current triage systems related
      to the on-site assignment of treatment status codes to a victim and the
      validation of the assigned code using actual patient outcomes. RESULTS: There is
      extensive literature published on triage systems used for MCI but only four
      articles used actual outcome data to validate mass casualty triage outcomes
      including three for chemical events. Currently, the amount and type of data
      collected are not consistent or standardized and definitions are not universal.
      CONCLUSIONS: Current literature does not provide needed evidence on the validity
      of triage systems for MCI in particular those involving chemicals. Well designed
      studies are needed to validate the reliability, sensitivity, and specificity of
      triage systems used for MCI including those involving chemicals.

PMID- 25068946
TI  - Effects of intervention to mild GDM on outcomes.
AB  - OBJECTIVE: To evaluate pregnancy outcomes in women with gestational diabetes
      mellitus (GDM) diagnosed by the IADPSG criteria at 24-28 weeks of gestation but
      with fasting plasma glucose (FPG) less than 4.4 mmol/L. RESEARCH DESIGN AND
      METHODS: A retrospective study was conducted. Medical records of 25,674 pregnant
      women attending the Peking University First Hospital (PUFH) were analyzed. Women
      with FPG value <4.4 mmol/L were segregated into those with and without GDM based
      on the IADPSG criteria. Pregnancy outcomes in the form of birth weight, neonatal
      hypoglycemia and cesarean delivery were compared between the two groups. RESULTS:
      The incidence of macrosomia between GDM 7.1% (treated 6.9%; untreated 7.2%) was
      not different from the non GDM group 6.3%, similarly neonatal hypoglycemia 1.9%
      (treated 2.0%; untreated 1.7%) was were not significantly different from the non
      GDM group 1.1%. Rate of cesarean delivery in the untreated GDM group 59.7% was
      significantly higher compared to both with treated GDM (48.4%) and the non GDM
      group (47.6%). CONCLUSIONS: There is no difference in the incidence of select
      adverse pregnancy outcomes amongst Chinese women with mild GDM (FPG<4.4 mmol/L)
      with or without intervention compared to women without GDM.

PMID- 25068947
TI  - Efficacy of tranexamic acid in decreasing blood loss in elective caesarean
      delivery.
AB  - OBJECTIVE: To evaluate the efficacy of tranexamic acid (TA) in decreasing blood
      loss during and after elective caesarean section (CS). METHODS: This prospective
      randomized trial was conducted among 124 pregnant women subjected to term
      elective CS. Patients were equally divided into two groups. Study group received
      10 mg/kg TA intravenously 5 min before skin incision while the control group did
      not. In addition, both groups received 10 units oxytocin and 1 ml ergometrine
      after delivery of the fetus. Blood loss in both groups was measured from
      placental delivery to end of the surgery and from end of the surgery to 2 h
      postpartum. Hemoglobin and hematocrit values were determined preoperatively and
      on the third day postpartum (before discharge) for all cases. Maternal and
      neonatal adverse effects in study groups were recorded. RESULTS: TA group showed
      lower amount of blood loss (391 ml) when compared to control group (597 ml). Risk
      estimation has revealed that treatment with TA resulted in decrease in risk of
      postpartum blood loss by 30%. Hemoglobin and hematocrit levels were significantly
      lower in the control group on the third post-operative day. CONCLUSION: TA
      reduces blood loss during and immediately after CS. Its use in caesarean delivery
      may be considered especially in cases where blood loss is expected to be high or
      in anemic patients.

PMID- 25068948
TI  - Fasting and postprandial glucose, insulin, leptin, and ghrelin values in preterm
      babies and their mothers: relationships among their levels, fetal growth, and
      neonatal anthropometry.
AB  - OBJECTIVE: To investigate relationship between anthropometric values of premature
      babies with their's glucose, insulin, leptin, and ghrelin at birth and on day 15.
      METHODS: We analyzed fasting and postprandial glucose, insulin, leptin, and
      ghrelin levels at birth and on day 15 in babies born prematurely between 24 and
      37 weeks, and who did not have serious problems aside from prematurity at birth.
      RESULTS: Fasting glucose, insulin, leptin and ghrelin values of babies at birth
      and on day 15 were significantly lower than postprandial values (all p values p <
      0.001). There were positive correlations between the mean insulin, leptin, and
      ghrelin levels with the gestational age, birth weight, body mass index, head
      circumference of babies at birth, and anthropometric values on day 15 (all r
      values > 0.400, all p values < 0.05). Fasting glucose, leptin, and ghrelin values
      of mothers birth were significantly lower than post-prandial values (all p values
      p < 0.05). CONCLUSIONS: The positive correlations between the insulin, leptin,
      and ghrelin values of babies at birth with gestational age and anthropometric
      values suggest that both hormones play important roles in fetal and neonatal
      growth and development.

PMID- 25068949
TI  - The utility of cervical elastosonography in prediction of cervical insufficiency:
      cervical elastosonography and cervical insufficiency.
AB  - OBJECTIVE: To evaluate the utility of cervical elastosonography (ES) in
      prediction of cervical insufficiency (CI). METHODS: A total of 40 women, of which
      20 who had previously received the diagnosis of CI and 20 healty women were
      included in the study. None of the women were pregnant. All subjects underwent
      sonographic evaluation including cervical length measurement and ES of uterine
      cervix. Adjacent muscular tissue was the reference point for elastosonography
      evaluation. Tissue strain ratio values were obtained from all the patients.
      RESULTS: The area around the internal cervical os of the group with CI was found
      to be significantly softer as compared to the control group (higher SR rate, p <
      0.05). Furthermore, the outer parts of the cervix (sites A and D) were also found
      harder in the group that had CI (lower SR rate, p < 0.05). CONCLUSIONS: According
      to our knowledge, this is preliminary study to evaluate the predictive value of
      cervical ES in CI and we concluded that ES can be used as reliable method to
      determine CI but it is necessary to be studied in different cohort groups.

PMID- 25068950
TI  - Novel strength test battery to permit evidence-based paralympic classification.
AB  - Ordinal-scale strength assessment methods currently used in Paralympic athletics
      classification prevent the development of evidence-based classification systems.
      This study evaluated a battery of 7, ratio-scale, isometric tests with the aim of
      facilitating the development of evidence-based methods of classification. This
      study aimed to report sex-specific normal performance ranges, evaluate test
      retest reliability, and evaluate the relationship between the measures and body
      mass.Body mass and strength measures were obtained from 118 participants-63 males
      and 55 females-ages 23.2 years +/- 3.7 (mean +/- SD). Seventeen participants
      completed the battery twice to evaluate test-retest reliability. The body mass
      strength relationship was evaluated using Pearson correlations and allometric
      exponents.Conventional patterns of force production were observed. Reliability
      was acceptable (mean intraclass correlation = 0.85). Eight measures had moderate
      significant correlations with body size (r = 0.30-61). Allometric exponents were
      higher in males than in females (mean 0.99 vs 0.30).Results indicate that this
      comprehensive and parsimonious battery is an important methodological advance
      because it has psychometric properties critical for the development of evidence
      based classification. Measures were interrelated with body size, indicating
      further research is required to determine whether raw measures require
      normalization in order to be validly applied in classification.

PMID- 25068951
TI  - Nationwide longitudinal analysis of acute liver failure in taiwan.
AB  - Acute liver failure (ALF) is uncommon but fatal. Current management is based
      mostly on clinical experience. We aimed to investigate the incidence, etiology,
      outcomes, and prognostic factors of ALF in Taiwan. Patients with the admission
      diagnosis of ALF between January 2005 and September 2007 were identified from the
      Longitudinal Health Insurance Database of Taiwan. ALF was further confirmed by
      disease severity based on laboratory orders, prescriptions, and duration of
      hospital stay, and acute onset without prior liver disease. Prognostic factors
      were identified using Cox regression analysis. During the study period, 218
      eligible cases were identified from 28,078 potential eligible ALF patients. The
      incidence was 80.2 per million person-years in average and increased with age.
      The mean age was 57.9 +/- 17.1 years and median survival was 171 days. The most
      common etiologies were viral (45.4%, mainly hepatitis B virus) and followed by
      alcohol/toxin (33.0%). Independent prognostic factors included alcohol
      consumption (hazard ratio, HR, 1.67 [1.01-2.77]), malignancy (HR 2.90 [1.92
      4.37]), frequency of checkups per week for total bilirubin (HR 1.57 [1.40-1.76]),
      sepsis (HR 1.85 [1.20-2.85]), and the use of hemodialysis/hemofiltration (HR 2.12
      [1.15-3.9]) and proton pump inhibitor (HR 0.94 [0.90-0.98]). Among the 130
      patients who survived >=90 days, 66 (50.8%) were complicated by liver cirrhosis.
      Eight (3.7%) were referred for liver transplantation evaluation, but only 1
      received transplantation and survived. ALF in Taiwan is mainly due to viral
      infection. Patients with malignancy and alcohol exposure have worst prognosis.
      The use of proton pump inhibitor is associated with improved survival. Half of
      the ALF survivors have liver cirrhosis. 

PMID- 25068952
TI  - Clinical uses of cervical vestibular-evoked myogenic potential testing in
      pediatric patients.
AB  - To demonstrate the feasibility and clinical significance of cervical vestibular
      evoked myogenic potential (cVEMP) test in pediatric patients.Retrospective review
      study was conducted in a pediatric tertiary care facility. A total of 278
      patients were identified with adequate data, including medical notes, results of
      cVEMP, and imaging studies.Among the total of 278 pediatric patients, only 3
      children were not able to finish the cVEMP test successfully. In about 90% of the
      cases, the cVEMP test was requested to investigate a patient's hearing loss
      and/or vestibular complaints. Over 90% of the cVEMP tests were ordered by
      specialists such as pediatric otolaryngologists or otologists. Obtained cVEMP
      results provided useful information in clinical diagnosis and management in all
      cases.It is feasible to conduct cVEMP testing in children, including infants, and
      cVEMP testing can provide valuable information in the diagnosis and management of
      hearing loss and vestibular impairment. This simple and noninvasive test should
      be embraced by pediatric professionals. 

PMID- 25068953
TI  - Rare giant T-wave inversions associated with myocardial stunning: report of 2
      cases.
AB  - Prominent T-wave inversions are well recognized electrocardiographic signs that
      can occur in acute myocardial infarction (AMI). However, the giant negative T
      waves may be associated with myocardial stunning without AMI.This case report
      describes 2 patients without AMI who developed rare giant T-wave inversions
      measuring up to 35 mm in depth and QT prolongation after admission to hospital.
      While 1 patient presented with acute pulmonary edema, the other patient presented
      with severe chest pain at rest and transient ST elevation.The giant T-wave
      inversion with QT prolongation may be caused by myocardial stunning due to the
      triple vessel diseases and elevated wall stress, high-end diastolic pressure and
      decreased coronary arterial flow during pulmonary edema in the first patient. The
      giant T-wave inversion with QT prolongation in the second patient may be caused
      by myocardial stunning due to the left anterior descending artery spasm
      (transient ST elevation) leading to transient total occlusion of left anterior
      descending artery. Percutaneous coronary intervention was successfully undergone
      for both patients. The patients remained well.The electrophysiologic mechanism
      responsible for giant T-wave inversion with QT prolongation is presently unknown.
      The two cases demonstrate that the rare giant negative T waves may be associated
      with myocardial stunning without AMI. 

PMID- 25068954
TI  - p53 dependent apoptotic cell death induces embryonic malformation in Carassius
      auratus under chronic hypoxia.
AB  - Hypoxia is a global phenomenon affecting recruitment as well as the embryonic
      development of aquatic fauna. The present study depicts hypoxia induced
      disruption of the intrinsic pathway of programmed cell death (PCD), leading to
      embryonic malformation in the goldfish, Carrasius auratus. Constant hypoxia
      induced the early expression of pro-apoptotic/tumor suppressor p53 and
      concomitant expression of the cell death molecule, caspase-3, leading to high
      level of DNA damage and cell death in hypoxic embryos, as compared to normoxic
      ones. As a result, the former showed delayed 4 and 64 celled stages and a delay
      in appearance of epiboly stage. Expression of p53 efficiently switched off
      expression of the anti-apoptotic Bcl-2 during the initial 12 hours post
      fertilization (hpf) and caused embryonic cell death. However, after 12 hours,
      simultaneous downregulation of p53 and Caspase-3 and exponential increase of Bcl
      2, caused uncontrolled cell proliferation and prevented essential programmed cell
      death (PCD), ultimately resulting in significant (p<0.05) embryonic malformation
      up to 144 hpf. Evidences suggest that uncontrolled cell proliferation after 12
      hpf may have been due to downregulation of p53 abundance, which in turn has an
      influence on upregulation of anti-apoptotic Bcl-2. Therefore, we have been able
      to show for the first time and propose that hypoxia induced downregulation of p53
      beyond 12 hpf, disrupts PCD and leads to failure in normal differentiation,
      causing malformation in gold fish embryos. 

PMID- 25068955
TI  - Efficacy evaluation of subtotal and total gastrectomies in robotic surgery for
      gastric cancer compared with that in open and laparoscopic resections: a meta
      analysis.
AB  - PURPOSES: Robotic gastrectomy (RG), as an innovation of minimally invasive
      surgical method, is developing rapidly for gastric cancer. But there is still no
      consensus on its comparative merit in either subtotal or total gastrectomy
      compared with laparoscopic and open resections. METHODS: Literature searches of
      PubMed, Embase and Cochrane Library were performed. We combined the data of four
      studies for RG versus open gastrectomy (OG), and 11 studies for robotic RG versus
      laparoscopic gastrectomy (LG). Moreover, subgroup analyses of subtotal and total
      gastrectomies were performed in both RG vs. OG and RG vs. LG. RESULTS: Totally 12
      studies involving 8493 patients met the criteria. RG, similar with LG,
      significantly reduced the intraoperative blood loss than OG. But the duration of
      surgery is longer in RG than in both OG and LG. The number of lymph nodes
      retrieved in RG was close to that in OG and LG (WMD = -0.78 and 95% CI, -2.15
      0.59; WMD = 0.63 and 95% CI, -2.24-3.51). And RG did not increase morbidity and
      mortality in comparison with OG and LG (OR = 0.92 and 95% CI, 0.69-1.23; OR =
      0.72 and 95% CI, 0.25-2.06) and (OR = 1.06 and 95% CI, 0.84-1.34; OR = 1.55 and
      95% CI, 0.49-4.94). Moreover, subgroup analysis of subtotal and total
      gastrectomies in both RG vs. OG and RG vs. LG revealed that the scope of surgical
      dissection was not a positive factor to influence the comparative results of RG
      vs. OG or LG in surgery time, blood loss, hospital stay, lymph node harvest,
      morbidity, and mortality. CONCLUSIONS: This meta-analysis highlights that robotic
      gastrectomy may be a technically feasible alternative for gastric cancer because
      of its affirmative role in both subtotal and total gastrectomies compared with
      laparoscopic and open resections.

PMID- 25068956
TI  - 210Pb and 210Po concentrations in Italian cigarettes and effective dose
      evaluation.
AB  - It has been known for a long time that cigarette tobacco contains naturally
      occurring radioactive nuclides such as 210Pb and 210Po. In this study, the
      concentrations of 210Pb and 210Po in the 10 most widely sold cigarette brands in
      Italy during the year 2010 were measured, and the effective dose to smokers has
      been calculated. The results of this study show that 210Pb concentration ranged
      from 11.6 to 20.0 mBq cig-1 with an arithmetic mean of 14.6 mBq cig-1, while the
      activity concentration of 210Po ranged from 13.1 to 19.0 mBq cig-1 with an
      arithmetic mean of 15.7 mBq cig-1, thus confirming previous results and showing
      that the radioactivity concentration was not reduced in the last few years. The
      annual effective dose for a typical smoker consuming 20 cigarettes per day ranged
      from an average of 55 MUSv y-1 to about 81 MUSv y-1. It is finally put in
      evidence the need to improve the knowledge about crucial data needed for accurate
      dose assessment deriving from the inhalation of both radioisotopes contained in
      the cigarettes, namely the dose conversion coefficients, which strongly depend on
      several parameters such as the inhalation speed through the mouth, the real
      fraction of radionuclide transferred from cigarette to mainstream smoke, the lung
      absorption behavior of the radioisotopes inhaled with mainstream smoke, and the
      AMAD of particles inhaled by smokers.

PMID- 25068957
TI  - Evaluation of the accuracy of dose delivery for IMRT based on transit dosimetry.
AB  - The authors have developed and evaluated a new method that uses transit dose in
      the treatment room in verification of dose delivery to patients. Five intensity
      modulated radiotherapy (IMRT) plans were selected from actual cancer patients,
      and transit dose was measured using MapCHECK 2 and an anthropomorphic phantom.
      The criteria used as a verification tool for the dose delivery to the patient
      were gamma-index-based dose comparison between the computed dose and measured
      dose. When the doses were delivered to an anthropomorphic phantom normally, the
      average passing rate was 95.2% based on a gamma index analysis. This feasibility
      study suggested that transit dose-based quality assurance can provide information
      about the accuracy of an inhomogeneity correction algorithm and patient
      positioning during treatment, allowing its use as a verification tool for actual
      dose delivery to patients in the treatment room. 

PMID- 25068958
TI  - Measurement of thoron exhalation rates from building materials.
AB  - Thoron (220Rn) exhalation from building materials has become increasingly
      recognized as a potential source for radiation exposure in dwellings. However,
      contrary to radon (220Rn), limited information on thoron exposure is available.
      The purpose of this study is to develop a test method for the determination of
      the thoron exhalation rate from building materials. The method is validated, and
      subsequently the thoron exhalation rates from 10 widely-applied concretes,
      gypsums, brick, limestone, and mortar are determined. The measured thoron
      exhalation rates of these materials range from 0.01 Bq m-2 s-1 to 0.43 Bq m-2 s
      1, with relative standard uncertainties between 6% to 14%.

PMID- 25068959
TI  - Comparison of the MACCS2 atmospheric transport model with Lagrangian puff models
      as applied to deterministic and probabilistic safety analysis.
AB  - The suitability of a new facility in terms of potential impacts from routine and
      accidental releases is typically evaluated using conservative models and
      assumptions to assure dose standards are not exceeded. However, overly
      conservative dose estimates that exceed target doses can result in unnecessary
      and costly facility design changes. This paper examines one such case involving
      the U.S. Department of Energy's pretreatment facility of the Waste Treatment and
      Immobilization Plant (WTP). The MELCOR Accident Consequence Code System Version 2
      (MACCS2) was run using conservative parameter values in prescribed guidance to
      demonstrate that the dose from a postulated airborne release would not exceed the
      guideline dose of 0.25 Sv. External review of default model parameters identified
      the deposition velocity of 1.0 cm s as being non-conservative. The deposition
      velocity calculated using resistance models was in the range of 0.1 to 0.3 cm s
      1. A value of 0.1 cm s-1 would result in the dose guideline being exceeded. To
      test the overall conservatism of the MACCS2 transport model, the 95th percentile
      hourly average dispersion factor based on one year of meteorological data was
      compared to dispersion factors generated from two state-of-the-art Lagrangian
      puff models. The 95th percentile dispersion factor from MACCS2 was a factor of 3
      to 6 higher compared to those of the Lagrangian puff models at a distance of 9.3
      km and a deposition velocity of 0.1 cm s-1. Thus, the inherent conservatism in
      MACCS2 more than compensated for the high deposition velocity used in the
      assessment. Applications of models like MACCS2 with a conservative set of
      parameters are essentially screening calculations, and failure to meet dose
      criteria should not trigger facility design changes but prompt a more in-depth
      analysis using probabilistic methods with a defined margin of safety in the
      target dose. A sample application of the probabilistic approach is provided.

PMID- 25068960
TI  - Assessment of self-help methods to reduce potential exposure to radiological
      contamination after a large-scale radiological release.
AB  - After the release of radioactive materials from a large radiological dispersal
      device (e.g., dirty bomb), improvised nuclear detonation, or nuclear power plant
      accident, up to hundreds of square miles may be contaminated. A portion of this
      area will be evacuated; however, people living in the portion that is not
      evacuated yet is still contaminated with low-levels of radioactive contamination
      will be asking for ways they can reduce their exposure. Whether cleaning
      activities can significantly reduce exposure is not fully understood. In this
      effort, the ability of cleaning activities to remove cesium (137Cs) was studied.
      The removal efficacy of cleaning with a commercial product, Simple Green(r), was
      compared to cleaning with water for hard surfaces typically seen in residences.
      The removal efficacy of laundering fabric material surfaces was also determined
      for a range of conditions (e.g., fabric material type, wash temperature). During
      these studies, assessments of the implications of these activities (e.g., cross
      contamination, resulting waste streams) were also completed. Simple Green and
      water were effective for removing 137Cs from plastic laminate and vinyl flooring
      (93.4-96.8%) but were not effective for removing 137Cs from painted wallboard and
      wood (7.3-68.1%). It was also determined that there was no significant difference
      between the two cleaners on all of the surfaces, except plastic laminate, for
      which Simple Green was slightly more effective. Laundering was effective for
      removing 137Cs contamination from polyester and cotton swatches and cotton
      comforters (up to 96.8% in the single swatch testing).

PMID- 25068961
TI  - Changes in the adhesion and migration ability of peripheral blood cells:
      potential biomarkers indicating exposure dose.
AB  - The expression of adhesion molecules and their related functions of adhesion and
      migration were investigated in peripheral blood mononuclear cells (PBMCs) to
      identify radiation-related changes and dose-dependency. The authors screened new
      biomarkers as radiation exposure dose indicators. Heparinized human peripheral
      blood was irradiated in vitro with different doses of gamma-rays. The expression
      levels of the CD11a, CD11b, CD18, CD29, CD49d, and CD54 molecules on the surface
      of PBMC cells were determined by flow cytometry at different time points post
      irradiation. The adhesion ability of human PBMCs was determined using an enzyme
      linked immunoassay kit, and the migration ability of rat PBMCs was evaluated
      using a transwell chamber assay. Compared with the unirradiated control group, a
      significant increase (p < 0.05) in human CD11b/CD13 double-positive cells was
      detected 6 h post 6 Gy irradiation in vitro. These results indicated that the
      decrease in human CD29/CD13 double-positive cells in the 6 Gy exposure group at
      6, 12, and 24 h post-irradiation was significant (p < 0.01). The adhesion ability
      of irradiated human PBMCs to IgG substrate increased significantly (p < 0.05) at
      6 h after irradiation of 2, 4, or 6 Gy compared with non-irradiated controls. The
      migration ability of the rat PBMCs toward the MIP-1alpha chemokine significantly
      decreased (p < 0.05) with increasing irradiation doses. These results suggest
      that the protein expression of cell surface molecules and their associated
      cellular functions might be potential biomarkers for identifying radiation
      exposure doses in an emergency radiation accident. 

PMID- 25068962
TI  - Clinical data from one year follow-up of victims of the radiation accident with
      60Co in Bulgaria.
AB  - A severe radiation accident occurred on 14 June 2011 in an industrial irradiation
      facility for medical equipment sterilization in Bulgaria. Five people were
      exposed for 5-10 min to a 60Co source containing 137 TBq. The Emergency
      Department of the National Centre of Radiobiology and Radiation Protection
      (NCRRP), Bulgaria, put into practice the plans for providing medical care in
      radiation accidents and the procedures developed for assessment of injury
      severity, the decision-making algorithm regarding subsequent treatment, and the
      therapy for persons affected. The activities performed for initial assessment of
      the severity of injury of irradiated patients were published in 2012. Based on
      predictive assessments of the severity of radiation damage, it was decided that
      the victims required hospitalization at a specialized hematology clinic. Percy
      Hospital in Paris was chosen for this purpose. The aim of this report is to
      present the results of 1-y follow-up for three of the victims. Sadly, 1 mo after
      the accident, Patient 4 died from a heart attack. The medical opinion was that
      this was not a direct outcome of the irradiation. Patient 5 was only followed up
      for 4 mo (118 d) because medical follow-up is voluntary, and despite repeated
      calls, the patient did not respond. Medical examinations by a physician as well
      as hematology and biochemical tests were performed using standard laboratory
      methods. The obtained results were compared to the victims' personal reference
      limits obtained from annual health monitoring. After the accident, the recovery
      to normal content of peripheral blood cells was observed in all victims.
      Nevertheless, there were observed cases of thrombocytopenia, granulocytopenia,
      and leucocytopenia at various times after exposure. During the period of
      observation, morphological changes in red blood cells such as anisomicrocitosis,
      macrocytes, megalocytes, and polychromatic erythrocytes were demonstrated. During
      the 1-y observation period, all victims showed immediate hematopoietic recovery
      within 2 mo after irradiation. Slight hypocellularity of bone marrow was noted at
      the end of the year.

PMID- 25068963
TI  - Analysis of the saturation phenomena of the neutralization rate of positively
      charged 218Po in water vapor.
AB  - Generally, 88% of the freshly generated 218Po ions decayed from 222Rn are
      positively charged. These positive ions become neutralized by recombination with
      negative ions, and the main source of the negative ions is the OH- ions formed by
      radiolysis of water vapor. However, the neutralization rate of positively charged
      218Po versus the square root of the concentration of H2O will be a constant when
      the concentration of H2O is sufficiently high. Since the electron affinity of the
      hydroxyl radical formed by water vapor is high, the authors propose that the
      hydroxyl radical can grab an electron to become OH-. Because the average period
      of collision with other positively charged ions and the average life of the OH-
      are much longer than those of the electron, the average concentration of negative
      ions will grow when the water vapor concentration increases. The authors obtained
      a model to describe the growth of OH- ions. From this model, it was found that
      the maximum value of the OH- ion concentration is limited by the square root of
      the radon concentration. If the radon concentration is invariant, the OH- ion
      concentration should be approximately a constant when the water vapor
      concentration is higher than a certain value. The phenomenon that the
      neutralization rate of positively charged 218Po versus the square root of the
      water vapor concentration will be saturated when the water vapor concentration is
      sufficiently high can be explained by this mechanism. This mechanism can be used
      also to explain the phenomenon that the detection efficiency of a radon monitor
      based on the electrostatic collection method seems to be constant when the water
      vapor concentration is high.

PMID- 25068964
TI  - Comment on ICNIRP guidelines for limiting exposure to electric fields induced by
      movement of the human body in a static magnetic field and by time-varying
      magnetic fields below 1 Hz.

PMID- 25068965
TI  - Response by ICNIRP to the comments of Gowland and Glover.

PMID- 25068966
TI  - Atomic bomb survivor cataract surgery prevalence data are consistent with non
      zero threshold dose--Comment on article by Nakashima et al. 2013.

PMID- 25068967
TI  - Response to Doss et al.

PMID- 25068972
TI  - Effect of 2-arachidonoylglycerol on myosin light chain phosphorylation and
      platelet activation: The role of phosphatidylinositol 3 kinase/AKT pathway.
AB  - The endocannabinoid 2-arachidonoylglycerol (2-AG) can be considered a true
      agonist as it is able to activate human platelets stimulating arachidonic acid
      release, thromboxane B2 formation and calcium intracellular elevation. Recently
      we have shown that 2-AG induces a rapid myosin light chain (MLC)
      phosphorylation/activation, early mediated by RhoA kinase (ROCK) signalling
      pathway and later by myosin light chain kinase. The aim of the present study was
      to investigate the role of phosphatidylinositol 3 kinase (PI3K)/AKT pathway in
      MLC phosphorylation and some downstream events such as actin polymerization, ATP
      secretion and aggregation. We demonstrated that PI3K in particular the isoforms
      alpha and beta and AKT have a role in MLC phosphorylation. The stimulation of
      PI3K/AKT pathway activates ROCK. ROCK is directly involved in the early phase of
      MLC activation stimulating thr18 phosphorylation. MLC activation is strengthened
      through the MLC phosphatase inhibition, that is accomplished through the
      phosphorylation of MYPT1, catalytic subunit of MLC phosphatase, overall mediated
      by ROCK. In addition we have found that the PI3Kalpha/beta isoforms and AKT are
      involved in the downstream mechanisms leading to actin polymerization, ATP
      secretion and aggregation of human platelets stimulated by 2-AG. 

PMID- 25068973
TI  - Radiofrequency ablation for chronic low back pain: a systematic review of
      randomized controlled trials.
AB  - BACKGROUND: Radiofrequency ablation (RFA), a procedure using heat to interrupt
      pain signals in spinal nerves, is an emerging treatment option for chronic low
      back pain. Its clinical efficacy has not yet been established. OBJECTIVE: To
      determine the efficacy of RFA for chronic low back pain associated with lumbar
      facet joints, sacroiliac joints, discogenic low back pain and the coccyx.
      METHODS: A systematic review was conducted. Medline, EMBASE, PubMed, SPORTDiscus,
      CINAHL and the Cochrane Library were searched up to August 2013. Abstracts and
      full-text articles were reviewed in duplicate. Included articles were sham
      controlled randomized controlled trials (RCTs), assessed the efficacy of RFA,
      reported at least one month of follow-up and included participants who had
      experienced back pain for at least three months. Data were extracted in duplicate
      and quality was assessed using the Cochrane Risk of Bias tool. Due to
      heterogeneity, as well as a lack of reported mean differences and SDs, meta
      analysis was not possible using these data. RESULTS: The present systematic
      review retrieved 1063 abstracts. Eleven sham-controlled RCTs were included: three
      studies involving discogenic back pain; six studies involving lumbar facet joint
      pain; and two studies involving sacroiliac joint pain. No studies were identified
      assessing the coccyx. The evidence supports RFA as an efficacious treatment for
      lumbar facet joint and sacroiliac joint pain, with five of six and both of the
      RCTs demonstrating statistically significant pain reductions, respectively. The
      evidence supporting RFA for the treatment of discogenic pain is mixed.
      CONCLUSIONS: While the majority of the studies focusing on lumbar facet joints
      and sacroiliac joints suggest that RFA significantly reduces pain in short-term
      follow-up, the evidence base for discogenic low back pain is mixed. There is no
      RCT evidence for RFA for the coccyx. Future studies should examine the clinical
      significance of the achieved pain reduction and the long-term efficacy of RFA.

PMID- 25068974
TI  - Metal-templated enantioselective enamine/H-bonding dual activation catalysis.
AB  - An octahedral bis-cyclometalated iridium(III) complex catalyzes the
      enantioselective alpha-amination of aldehydes with catalyst loadings down to 0.1
      mol%. In this metal-templated design, the metal serves as a structural center and
      provides the exclusive source of chirality, whereas the catalysis is mediated
      through the organic ligand sphere.

PMID- 25068975
TI  - Serial ultrasonographic evaluation of ovarian abnormalities with a morphology
      index.
AB  - OBJECTIVE: Transvaginal ultrasonography with tumor morphology index (MI) has been
      used to predict the risk of ovarian malignancy. Our objective was to analyze
      changes in serial MI scores for malignant and non-malignant ovarian tumors in a
      large and asymptomatic population. METHODS: Eligible subjects participated in the
      University of Kentucky Ovarian Cancer Screening Program and had abnormalities
      that included cysts, cysts with septations, complex cysts with solid areas, and
      solid masses. Analysis included: MI, change in MI (delta MI), delta MI per scan
      and per month, number and duration of scans. RESULTS: From 1987 to 2012, 38,983
      women received 218,445 scans. Of the 7104 eligible subjects, 6758 tumors were
      observed without surgery and 472 were surgically removed. Eighty-six percent
      (5811) of observed tumors were resolved. There were 74 malignant and 272 non
      malignant tumors. Eighty-five percent of malignancies had MI >=5 at decision for
      surgery. The risk of malignancy based on MI was: MI=5 (3%), MI=6 (3.7%), MI=7
      (12.6%), MI=8 (26.7%), MI=9 (27.8%), MI=10 (33.3%). The mean delta MI per month
      decreased for tumors that resolved (delta MI -1.0, p<0.001) or persisted without
      surgery (delta MI -0.7, p<0.001). For abnormalities surgically removed, the mean
      delta MI per month increased significantly more for malignancies than for benign
      tumors (delta MI +1.6 vs. +0.3, p<0.001). CONCLUSIONS: The mean MI for malignant
      ovarian tumors increases over time, while non-malignant tumors have a decreasing
      or stable MI. Serial MI analysis can improve the prediction of ovarian malignancy
      by reducing false-positive results, thereby decreasing the number of operations
      performed for benign abnormalities.

PMID- 25068976
TI  - Self-powered pH sensor based on a flexible organic-inorganic hybrid composite
      nanogenerator.
AB  - In this study, we developed an innovative, flexible, organic-inorganic hybrid
      composite nanogenerator, which was used to drive a self-powered microwire-based
      pH sensor. The hybrid composite nanogenerator was fabricated using ZnO nanowire
      and piezoelectric polymer poly(vinylidene fluoride), through a simple,
      inexpensive solution-casting technique. The fabricated hybrid composite
      nanogenerator delivered a maximum open-circuit voltage of 6.9 V and a short
      circuit current of 0.96 MUA, with an output power of 6.624 MUW under uniaxial
      compression. This high-performance, electric poling free composite nanogenerator
      opens up the possibility of industrial-scale fabrication. The hybrid
      nanogenerator demonstrated its ability to drive five green LEDs simultaneously,
      without using an energy-storage device. Additionally, we constructed a self
      powered pH sensor, using a ZnO microwire powered with our hybrid nanogenerator.
      The output voltage varied according to changes in the pH level. This study
      demonstrates the feasibility of using a hybrid nanogenerator as a self-powered
      device that can be extended for use as a biosensor for environmental monitoring
      and/or as a smart, wearable, vibration sensor in future applications. 

PMID- 25068977
TI  - Enhanced CO2 permeability of membranes by incorporating polyzwitterion@CNT
      composite particles into polyimide matrix.
AB  - In this study, polyzwitterion is introduced into a CO2 separation membrane.
      Composite particles of polyzwitterion coated carbon nanotubes (SBMA@CNT) are
      prepared via a precipitation polymerization method. Hybrid membranes are
      fabricated by incorporating SBMA@CNT in polyimide matrix and utilized for CO2
      separation. The prepared composite particles and hybrid membranes are
      characterized by transmission electron microscopy (TEM) with element mapping,
      field emission scanning electron microscopy (FESEM), Fourier transform infrared
      (FTIR) spectra, differential scanning calorimetry (DSC) and an electronic tensile
      machine. Water uptake and water state of membranes are measured to probe the
      relationship among water uptake, water state and CO2 transport behavior. Hybrid
      membranes show significantly enhanced CO2 permeability compared to an unfilled
      polyimide membrane at a humidified state. A hybrid membrane with 5 wt % SBMA@CNT
      exhibits the maximum CO2 permeability of 103 Barrer with a CO2/CH4 selectivity of
      36. The increase of CO2 permeability is attributed to the incorporation of the
      SBMA@CNT composite particles. First, SBMA@CNT form interconnected channels for
      CO2 transport due to the facilitated transport effect of the quaternary ammonium
      in repeat unit of pSBMA. Second, SBMA@CNT improve water uptake and adjust water
      state of membrane, which further increases CO2 permeability. Meanwhile, the
      variation of CO2/CH4 selectivity is dependent on the bound water portion in the
      membrane. A gas permeation test at a dry state and a pressure test are conducted
      to further probe the membrane separation performance. 

PMID- 25068978
TI  - Lifetime victimization and physical health outcomes among lesbian and
      heterosexual women.
AB  - BACKGROUND: Lifetime victimization experiences, including child sexual abuse
      (CSA), child physical abuse (CPA), adult sexual assault (ASA), and adult physical
      assault (APA), are associated with health problems. PURPOSE: To examine
      relationships between cumulative victimization and physical health among
      heterosexual and lesbian women and determine whether these relationships differ
      by sexual identity. METHODS: Large samples of heterosexual (n = 482) and lesbian
      women (n = 394) were interviewed. Questions included lifetime victimization
      experiences and physical health problems. RESULTS: Compared to women who reported
      no childhood victimization, those who reported experiencing both CSA and CPA were
      44% more likely to report health problems and women who experienced all four
      types of victimization (CSA, CPA, APA, ASA) were nearly 240% as likely to report
      physical health problems. Interaction analyses revealed the association between
      victimization and physical health did not differ by sexual identity. CONCLUSIONS:
      Although lesbians were more likely to report all types of victimization, results
      suggest that victimization conferred increased physical health risks regardless
      of sexual identity.

PMID- 25068979
TI  - Rare diseases. Foreword.

PMID- 25068980
TI  - Glucocerebrosidase inhibitors: future drugs for the treatment of Gaucher disease?

PMID- 25068981
TI  - What are the most promising emerging therapies for sickle cell disease?

PMID- 25068983
TI  - The discovery of medicines for rare diseases.
AB  - There is a pressing need for new medicines (new molecular entities; NMEs) for
      rare diseases as few of the 6800 rare diseases (according to the NIH) have
      approved treatments. Drug discovery strategies for the 102 orphan NMEs approved
      by the US FDA between 1999 and 2012 were analyzed to learn from past success: 46
      NMEs were first in class; 51 were followers; and five were imaging agents. First
      in-class medicines were discovered with phenotypic assays (15), target-based
      approaches (12) and biologic strategies (18). Identification of genetic causes in
      areas with more basic and translational research such as cancer and in-born
      errors in metabolism contributed to success regardless of discovery strategy. In
      conclusion, greater knowledge increases the chance of success and empirical
      solutions can be effective when knowledge is incomplete. 

PMID- 25068984
TI  - GALK inhibitors for classic galactosemia.
AB  - Classic galactosemia is an inherited metabolic disease for which, at present, no
      therapy is available apart from galactose-restricted diet. However, the efficacy
      of the diet is questionable, since it is not able to prevent the insurgence of
      chronic complications later in life. In addition, it is possible that dietary
      restriction itself could induce negative side effects. Therefore, there is a need
      for an alternative therapeutic approach that can avert the manifestation of
      chronic complications in the patients. In this review, the authors describe the
      development of a novel class of pharmaceutical agents that target the production
      of a toxic metabolite, galactose-1-phosphate, considered as the main culprit for
      the cause of the complications, in the patients. 

PMID- 25068985
TI  - Multitarget ligands and theranostics: sharpening the medicinal chemistry sword
      against prion diseases.
AB  - Prion diseases (PrDs) are fatal neurodegenerative disorders, for which no
      effective therapeutic and diagnostic tools exist. The main pathogenic event has
      been identified as the misfolding of a disease-associated prion protein.
      Nevertheless, pathogenesis seems to involve an intricate array of concomitant
      processes. Thus, it may be unlikely that drugs acting on single targets can
      effectively control PrDs. In addition, diagnosis occurs late in the disease
      process, by which point it is difficult to determine a successful therapeutic
      intervention. In this context, multitarget ligands (MTLs) and theranostic ligands
      (TLs) emerge for their potential to effectively cure and diagnose PrDs. In this
      review, we discuss the medicinal chemistry challenges of identifying novel MTLs
      and TLs against PrDs, and envision their impact on prion drug discovery. 

PMID- 25068986
TI  - Pharmacological chaperone therapy for lysosomal storage diseases.
AB  - Pharmacological chaperone therapy is an emerging approach to treat lysosomal
      storage diseases. Small-molecule chaperones interact with mutant enzymes, favor
      their correct conformation and enhance their stability. This approach shows
      significant advantages when compared with existing therapies, particularly in
      terms of the bioavailability of drugs, oral administration and positive impact on
      the quality of patients' lives. On the other hand, future research in this field
      must confront important challenges. The identification of novel chaperones is
      indispensable to expanding the number of patients amenable to this treatment and
      to optimize therapeutic efficacy. It is important to develop new allosteric
      drugs, to address the risk of inhibiting target enzymes. Future research must
      also be directed towards the exploitation of synergies between chaperone
      treatment and other therapeutic approaches. 

PMID- 25068987
TI  - Therapeutic targeting of misfolding and conformational change in alpha1
      antitrypsin deficiency.
AB  - Misfolding and conformational diseases are increasing in prominence and
      prevalence. Both misfolding and 'postfolding' conformational mechanisms can
      contribute to pathogenesis and can coexist. The different contexts of folding and
      native state behavior may have implications for the development of therapeutic
      strategies. alpha1-antitrypsin deficiency illustrates how these issues can be
      addressed with therapeutic approaches to rescue folding, ameliorate downstream
      consequences of aberrant polymerization and/or maintain physiological function.
      Small-molecule strategies have successfully targeted structural features of the
      native conformer. Recent developments include the capability to follow solution
      behavior of alpha1-antitrypsin in the context of disease mutations and
      interactions with drug-like compounds. Moreover, preclinical studies in cells and
      organisms support the potential of manipulating cellular response repertoires to
      process misfolded and polymer states. 

PMID- 25068988
TI  - Progress towards next-generation therapeutics for cystic fibrosis.
AB  - Cystic fibrosis (CF) is the most common inherited genetic condition amongst
      Caucasian ethnicities, affecting 1 in 2500 live births. There remains a
      significant unmet medical need for more and better therapies for this chronic,
      degenerative condition, in particular those that address the respiratory
      dysfunction and respiratory infections that characterise CF. CF is caused by
      mutations in the cystic transmembrane conductance regulator gene (CFTR). The key
      pathology driver of CF is dysregulated ion transport across the epithelial cell
      barriers that line the respiratory tract, gastrointestinal tract and other organ
      systems. This review focuses on the state-of-the-art advances and future
      directions in therapeutic strategies to combat and manage the symptoms of CF
      and/or restore functionality of the defective CFTR. 

PMID- 25068990
TI  - Health care development: integrating transaction cost theory with social support
      theory.
AB  - The emergence of Web 2.0 technologies has already been influential in many
      industries, and Web 2.0 applications are now beginning to have an impact on
      health care. These new technologies offer a promising approach for shaping the
      future of modern health care, with the potential for opening up new opportunities
      for the health care industry as it struggles to deal with challenges including
      the need to cut costs, the increasing demand for health services and the
      increasing cost of medical technology. Social media such as social networking
      sites are attracting more individuals to online health communities, contributing
      to an increase in the productivity of modern health care and reducing transaction
      costs. This study therefore examines the potential effect of social technologies,
      particularly social media, on health care development by adopting a social
      support/transaction cost perspective. Viewed through the lens of Information
      Systems, social support and transaction cost theories indicate that social media,
      particularly online health communities, positively support health care
      development. The results show that individuals join online health communities to
      share and receive social support, and these social interactions provide both
      informational and emotional support.

PMID- 25068991
TI  - Long hydrophilic-and-cationic polymers: a different pathway toward preferential
      activity against bacterial over mammalian membranes.
AB  - We show that simply converting the hydrophobic moiety of an antimicrobial peptide
      (AMP) or synthetic mimic of AMPs (SMAMP) into a hydrophilic one could be a
      different pathway toward membrane-active antimicrobials preferentially acting
      against bacteria over host cells. Our biostatistical analysis on natural AMPs
      indicated that shorter AMPs tend to be more hydrophobic, and the hydrophilic-and
      cationic mutants of a long AMP experimentally demonstrated certain membrane
      activity against bacteria. To isolate the effects of antimicrobials'
      hydrophobicity and systematically examine whether hydrophilic-and-cationic
      mutants could inherit the membrane activity of their parent AMPs/SMAMPs, we
      constructed a minimal prototypical system based on methacrylate-based polymer
      SMAMPs and compared the antibacterial membrane activity and hemolytic toxicity of
      analogues with and without the hydrophobic moiety. Antibacterial assays showed
      that the hydrophobic moiety of polymer SMAMPs consistently promoted the
      antibacterial activity but diminished in effectiveness for long polymers, and the
      resultant long hydrophilic-and-cationic polymers were also membrane active
      against bacteria. What distinguished these long mutants from their parent SMAMPs
      were their drastically reduced hemolytic toxicities and, as a result, strikingly
      enhanced selectivity. Similar toxicity reduction was observed with the
      hydrophilic-and-cationic mutants of long AMPs. Taken together, our results
      suggest that long hydrophilic-and-cationic polymers could offer preferential
      membrane activity against bacteria over host cells, which may have implications
      in future antimicrobial development. 

PMID- 25068989
TI  - Advances in therapeutic development for spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. The
      disease originates from low levels of SMN protein due to deletion and/or
      mutations of SMN1 coupled with the inability of SMN2 to compensate for the loss
      of SMN1. While SMN1 and SMN2 are nearly identical, SMN2 predominantly generates a
      truncated protein (SMNDelta7) due to skipping of exon 7, the last coding exon.
      Several avenues for SMA therapy are being explored, including means to enhance
      SMN2 transcription, correct SMN2 exon 7 splicing, stabilize SMN/SMNDelta7
      protein, manipulate SMN-regulated pathways and SMN1 gene delivery by viral
      vectors. This review focuses on the aspects of target discovery, validations and
      outcome measures for a promising therapy of SMA. 

PMID- 25068992
TI  - Bufotalin-induced apoptosis in osteoblastoma cells is associated with endoplasmic
      reticulum stress activation.
AB  - The search for novel and more efficient chemo-agents against malignant
      osteoblastoma is important. In this study, we examined the potential anti
      osteoblastoma function of bufotalin, and studied the underlying mechanisms. Our
      results showed that bufotalin induced osteoblastoma cell death and apoptosis in
      dose- and time-dependent manners. Further, bufotalin induced endoplasmic
      reticulum (ER) stress activation in osteoblastoma cells, the latter was detected
      by the induction of C/EBP homologous protein (CHOP), phosphorylation of inositol
      requiring enzyme 1 (IRE1) and PKR-like endoplasmic reticulum kinase (PERK), as
      well as caspase-12 activation. Conversely, the ER stress inhibitor salubrinal,
      the caspase-12 inhibitor z-ATAD-fmk as well as CHOP depletion by shRNA
      significantly inhibited bufotalin-induced osteoblastoma cell death and apoptosis.
      Finally, by using a mice xenograft model, we demonstrated that bufotalin
      inhibited U2OS osteoblastoma cell growth in vivo. In summary, our results suggest
      that ER stress contributes to bufotalin-induced apoptosis in osteoblastoma cells.
      Bufotalin might be investigated as a novel anti-osteoblastoma agent. 

PMID- 25068993
TI  - A potent cyclic peptide targeting SPSB2 protein as a potential anti-infective
      agent.
AB  - The protein SPSB2 mediates proteosomal degradation of inducible nitric oxide
      synthase (iNOS). Inhibitors of SPSB2-iNOS interaction may prolong the lifetime of
      iNOS and thereby enhance the killing of persistent pathogens. We have designed a
      cyclic peptide, Ac-c[CVDINNNC]-NH2, containing the key sequence motif mediating
      the SPSB2-iNOS interaction, which binds to the iNOS binding site on SPSB2 with a
      Kd of 4.4 nM, as shown by SPR, [(1)H,(15)N]-HSQC, and (19)F NMR. An in vitro
      assay on macrophage cell lysates showed complete inhibition of SPSB2-iNOS
      interactions by the cyclic peptide. Furthermore, its solution structure closely
      matched (backbone rmsd 1.21 A) that of the SPSB2-bound linear DINNN peptide. The
      designed peptide was resistant to degradation by the proteases pepsin, trypsin,
      and chymotrypsin and stable in human plasma. This cyclic peptide exemplifies
      potentially a new class of anti-infective agents that acts on the host innate
      response, thereby avoiding the development of pathogen resistance. 

PMID- 25068994
TI  - The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer.
AB  - The post-transcriptional control of gene expression mediated by RNA-binding
      proteins (RBPs), long non-coding RNAs (lncRNAs) as well as miRNAs is essential to
      determine tumor cell fate and thus is a major determinant in cancerogenesis. The
      IGF2 mRNA binding protein family (IGF2BPs) comprises three RBPs. Two members of
      the family, IGF2BP1 and IGF2BP3, are bona fide oncofetal proteins, which are de
      novo synthesized in various human cancers. In vitro studies revealed that IGF2BPs
      serve as post-transcriptional fine-tuners modulating the expression of genes
      implicated in the control of tumor cell proliferation, survival, chemo-resistance
      and metastasis. Consistently, the expression of both IGF2BP family members was
      reported to correlate with an overall poor prognosis and metastasis in various
      human cancers. Due to the fact that most reports used a pan-IGF2BP antibody for
      studying IGF2BP expression in cancer, paralogue-specific functions can barely be
      evaluated at present. Nonetheless, the accordance of IGF2BPs' role in promoting
      an aggressive phenotype of tumor-derived cells in vitro and their upregulated
      expression in aggressive malignancies provides strong evidence that IGF2BPs are
      powerful post-transcriptional oncogenes enhancing tumor growth, drug-resistance
      and metastasis. This suggests IGF2BPs as powerful biomarkers and candidate
      targets for cancer therapy.

PMID- 25068995
TI  - The receptor tyrosine kinase ROR1--an oncofetal antigen for targeted cancer
      therapy.
AB  - Targeted cancer therapies have emerged as new treatment options for various
      cancer types. Among targets, receptor tyrosine kinases (RTKs) are among the most
      promising. ROR1 is a transmembrane RTK of importance during the normal
      embryogenesis for the central nervous system, heart, lung and skeletal systems,
      but is not expressed in normal adult tissues. However, ROR1 is overexpressed in
      several human malignancies and may act as a survival factor for tumor cells. Its
      unique expression by malignant cells may provide a target for novel therapeutics
      including monoclonal antibodies (mAbs) and small molecule inhibitors of tyrosine
      kinases (TKI) for the treatment of cancer. Promising preclinical results have
      been reported in e.g. chronic lymphocytic leukemia, pancreatic carcinoma, lung
      and breast cancer. ROR1 might also be an interesting oncofetal antigen for active
      immunotherapy. In this review, we provide an overview of the ROR1 structure and
      functions in cancer and highlight emerging therapeutic options of interest for
      targeting ROR1 in tumor therapy.

PMID- 25068996
TI  - FOXM1: A key oncofoetal transcription factor in health and disease.
AB  - Forkhead Box M1 (FOXM1) is a bona fide oncofoetal transcription factor, which
      orchestrates complex temporal and spatial gene expression throughout embryonic
      and foetal development as well as during adult tissue homeostasis and repair.
      Controlled FOXM1 expression and activity provides a balanced transcriptional
      programme to ensure proper growth and maturation during embryogenesis and foetal
      development as well as to manage appropriate homeostasis and repair of adult
      tissues. Conversely, deregulated FOXM1 upregulation likely affects cell
      migration, invasion, angiogenesis, stem cell renewal, DNA damage repair and
      cellular senescence, which impact tumour initiation, progression, metastasis,
      angiogenesis and drug resistance. A thorough understanding of the regulation and
      role of FOXM1 in health and in cancer should contribute to the development of
      better diagnostics and treatments for cancer as well as congenital disorders and
      other developmental diseases.

PMID- 25068997
TI  - Characterization of biases in phosphopeptide enrichment by Ti(4+)-immobilized
      metal affinity chromatography and TiO2 using a massive synthetic library and
      human cell digests.
AB  - Outcomes of comparative evaluations of enrichment methods for phosphopeptides
      depend highly on the experimental protocols used, the operator, the source of the
      affinity matrix, and the samples analyzed. Here, we attempt such a comparative
      study exploring a very large synthetic library containing thousands of serine,
      threonine, and tyrosine phosphorylated peptides, being present in roughly equal
      abundance, along with their nonphosphorylated counterparts, and use an optimized
      protocol for enrichment by TiO2 and Ti(4+)-immobilized metal affinity
      chromatography (IMAC) by a single operator. Surprisingly, our data reveal that
      there are minimal differences between enrichment of phosphopeptides by TiO2 and
      Ti(4+)-IMAC when considering biochemical and biophysical parameters such as
      peptide length, sequence surrounding the site, hydrophobicity, and nature of the
      amino acid phosphorylated. Similar results were obtained when evaluating a
      tryptic digest of a cellular lysate, representing a more natural source of
      phosphopeptides. All the data presented are available via ProteomeXchange with
      the identifier PXD000759. 

PMID- 25068998
TI  - Early effect of hydroxychloroquine therapy: relationship between cumulative dose
      and retinal thickness.
AB  - BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of
      autoimmune diseases such as rheumatoid arthritis. However, its long-term use is
      known to be associated with visual changes due to retinal damage. Retinal damage
      associated with long-term HCQ therapy is preventable if the drug is discontinued
      early when the patients are still asymptomatic. In view of contrasting reports
      from previous studies, we investigated the association of prolonged HCQ therapy
      with retinal thickness in macular area. METHODS: This study included 48 patients
      on long-term HCQ therapy and 38 healthy controls. All subjects underwent
      examination for corrected visual acuity, fundus photography, visual fields and SD
      OCT for retinal thickness. RESULTS: Visual acuity, visual fields, fundus
      photography and SD-OCT did not reveal changes consistent with diagnosis of
      established HCQ retinopathy in any of the subjects from HCQ group. Retinal
      thickness in central, parafoveal and perifoveal areas did not show significant
      differences between HCQ and control groups. However, we observed negative
      correlation between cumulative dose and retinal thickness in the parafoveal (p =
      0.003) and perifoveal areas (p = 0.019) but not in the central area. CONCLUSIONS:
      Correlation of cumulative dose with retinal thickness in parafoveal and
      perifoveal areas and not the central area is in accordance with the late
      appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic
      patients using OCT seems to be of great importance for early detection of retinal
      changes.

PMID- 25068999
TI  - A case of generalized allergic contact dermatitis after laser tattoo removal.
AB  - Tattoos are popular body decorations mainly done for cosmetic purposes. Regarded
      as a form of self-expression, tattoos reflect the character of the person wearing
      it. However, as tatoos are persistent visual markings on the body, frequently
      misperceived by the others causing tattooed to seek removal. Today most of the
      tattoos can be successfully treated with laser ablation. Here we present a case
      of generalized allergic contact dermatitis after laser tattoo removal which is a
      rare adverse reaction of laser tattoo removal. 

PMID- 25069000
TI  - Ciliary body toxicities of systemic oxcarbazepine and valproic acid treatments:
      electron microscopic study.
AB  - Ciliary body is responsible for humour aqueous production in posterior chamber.
      Valproic acid (VPA) has been widely used for the treatment of epilepsy and other
      neuropsychiatric diseases such as bipolar disease and major depression.
      Oxcarbazepine (OXC) is a new anti-epileptic agent that has been used recently for
      childhood epilepsies such as VPA. In this study, we aimed to investigate the
      effects of VPA and OXC treatments used as antiepileptic in ciliary body by
      electron microscopy. In our study, 40 Wistar rats (21 days old) were divided
      equally into four groups which were applied saline (group 1), VPA (group 2), OXC
      (group 3) and VPA + OXC (group 4). The as-prepared ocular tissues were
      characterized by transmission electron microscopy (TEM) technique in scanning and
      transmission electron microscopy (SEM-TEM) (Carl Zeiss EVO LS10). The results
      confirmed that VPA caused dense ciliary body degeneration. Additionally, ciliary
      body degeneration in group 4 was supposed to be due to VPA treatment. Ciliary
      body damage and secondary outcomes should be considered in patients with long
      term VPA therapy. 

PMID- 25069001
TI  - Skin sensitivity and intolerance in Shanghai: cumulative influence of different
      meteorological parameters.
AB  - BACKGROUND: Although Sensitive skin (SS) conditions are reported to be affected
      by climate changes, the correlations with meteorological parameters remain mostly
      unclear. OBJECTIVE: To investigate the changes of facial skin conditions in
      different seasons in Shanghai, including the speed and severity of the influences
      imposed by different meteorological parameters. METHODS: Totally eighty-one
      healthy female volunteers completed the study in both spring (May) and summer
      (August). Evaluations of facial skin conditions included stimulating sensory
      test, clinical grading and biophysical measurements. Correlations between the
      meteorological parameters and DeltaTEWL as well as clinical parameters were
      analyzed. RESULTS: There was no significant difference between two seasons in
      lactic acid sting test. The stimulation sensations felt by Vitamin B3 (VB3)
      containing cream was significantly higher in May than that in August. In
      accordance, baseline visual scores for erythema and scaliness in May were also
      significantly higher than those scores in August. The baseline transepidermal
      water loss (TEWL) value was significantly higher in May than that in August.
      Positive correlations were detected between DeltaTEWL and atmospheric pressure on
      the test day, adjust 3-day and 7-day mean of daily solar radiation respectively.
      There were negative correlations between DeltaTEWL and temperature outside on the
      test day, adjust 3-day mean as well as adjust 7-day mean of relative humidity.
      CONCLUSIONS: Facial skin conditions in summer are better than that in spring in
      Shanghai. The influences from atmospheric pressure and temperature are relatively
      quick in speed, while the influences from relative humidity and solar radiation
      are slow but cumulative.

PMID- 25069002
TI  - Ocular surface changes following botulinum toxin injection for strabismus.
AB  - CONTEXT: Botulinum toxin injection is widely used for many purposes, including
      neuromuscular diseases, movement disorders and strabismus. OBJECTIVE: To evaluate
      and report the impact of botulinum toxin injection on ocular surface parameters
      in patients with strabismus. PARTICIPANTS: Twenty-six consecutive patients who
      underwent botulinum toxin A injection for ocular misalignment were recruited for
      this prospective study. MATERIALS AND METHODS: Testing of ocular surface
      parameters including tear break-up time (BUT), lissamine green (LG) staining and
      Schirmer test (under topical anesthesia) was performed, and Ocular Surface
      Disease Index (OSDI) questionnaire scores were recorded before and at certain
      time points after injection (one week, two weeks, one month, three months and six
      months after botulinum toxin A injection). Two-way analysis of variance (ANOVA)
      with repeated measures, Friedman's test and Wilcoxon test were used for
      statistical analysis. RESULTS: Twenty six patients (15 eso- and 11 exo
      deviations) with a mean age of 32.46 +/- 14.41 (17-65) years were recruited for
      the study. All injections were performed in one eye. The mean amount of deviation
      at near and distance reduced after injection. The change of BUT, LG staining and
      OSDI scores was found to be significant during follow-up in treated eyes (p =
      0.001, p = 0.007 and p = 0.009, respectively) whereas the change was
      insignificant for the Schirmer test results (p = 0.266). CONCLUSIONS: The ocular
      surface parameters appear to be altered by botulinum toxin injection in
      strabismic patients. Even though these effects seemed to be temporary, the
      findings of the present study support the notion of botulinum toxin effects on
      ocular surface parameters.

PMID- 25069003
TI  - Kinetics and mechanism of the tropospheric reaction of 3-hydroxy-3-methyl-2
      butanone with Cl atoms.
AB  - The relative rate coefficient for the gas-phase reaction of 3-hydroxy-3-methyl-2
      butanone (3H3M2B) with Cl atoms was determined under atmospheric conditions (298
      +/- 2 K, 720 +/- 2 Torr). The products of the reaction were identified and
      quantified. This work provides the first kinetic and mechanistic determinations
      of the gas-phase reaction of Cl atoms with 3H3M2B. The rate measurements and the
      products studies were performed in two simulation chambers coupled to the gas
      chromatography-mass spectrometer (GC-MS) and the Fourier transform infrared
      (FTIR) techniques, respectively. The obtained average rate coefficient was (1.13
      +/- 0.17) * 10(-10) cm(3) molecule(-1) s(-1) using propene and 1,3-butadiene as
      reference compounds. The major primary reaction products observed in this study
      were (with % molar yields): acetic acid (42.6 +/- 4.8) and 2,3-butanedione (17.2
      +/- 2.3). Results and mechanism are discussed in terms of the structure
      reactivity relationship and compared with the reported reactivity with the other
      atmospheric oxidants. The atmospheric implications derived from this study are
      discussed as well. 

PMID- 25069004
TI  - Sunscreens as a source of hydrogen peroxide production in coastal waters.
AB  - Sunscreens have been shown to give the most effective protection for human skin
      from ultraviolet (UV) radiation. Chemicals from sunscreens (i.e., UV filters)
      accumulate in the sea and have toxic effects on marine organisms. In this report,
      we demonstrate that photoexcitation of inorganic UV filters (i.e., TiO2 and ZnO
      nanoparticles) under solar radiation produces significant amounts of hydrogen
      peroxide (H2O2), a strong oxidizing agent that generates high levels of stress on
      marine phytoplankton. Our results indicate that the inorganic oxide nanoparticle
      content in 1 g of commercial sunscreen produces rates of H2O2 in seawater of up
      to 463 nM/h, directly affecting the growth of phytoplankton. Conservative
      estimates for a Mediterranean beach reveal that tourism activities during a
      summer day may release on the order of 4 kg of TiO2 nanoparticles to the water
      and produce an increment in the concentration of H2O2 of 270 nM/day. Our results,
      together with the data provided by tourism records in the Mediterranean, point to
      TiO2 nanoparticles as the major oxidizing agent entering coastal waters, with
      direct ecological consequences on the ecosystem. 

PMID- 25069005
TI  - Recommendations from the Association of European Paediatric Cardiology for
      training in diagnostic and interventional cardiac catheterisation.
AB  - Cardiac catheterisation in congenital heart disease is a developing field.
      Patients' ages range from foetus to adulthood. This document is a revision and
      update of the previously published recommendations and summarises the
      requirements for training in diagnostic and interventional cardiac
      catheterisation. 

PMID- 25069006
TI  - Immobilization of gold nanoparticles on cell culture surfaces for safe and
      enhanced gold nanoparticle-mediated laser transfection.
AB  - In comparison to standard transfection methods, gold nanoparticle-mediated laser
      transfection has proven to be a versatile alternative. This is based on its minor
      influence on cell viability and its high efficiency, especially for the delivery
      of small molecules like small interfering RNA. However, in order to transfer it
      to routine usage, a safety aspect is of major concern: The avoidance of
      nanoparticle uptake by the cells is desired. The immobilization of the gold
      nanoparticles on cell culture surfaces can address this issue. In this study, we
      achieved this by silanization of the appropriate surfaces and the binding of gold
      nanoparticles to them. Comparable perforation efficiencies to the previous
      approaches of gold nanoparticle-mediated laser transfection with free gold
      nanoparticles are demonstrated. The uptake of the immobilized particles by the
      cells is unlikely. Consequently, these investigations offer the possibility of
      bringing gold nanoparticle-mediated laser transfection closer to routine usage.

PMID- 25069007
TI  - Investigation of influences of the paraformaldehyde fixation and paraffin
      embedding removal process on refractive indices and scattering properties of
      epithelial cells.
AB  - The scattering properties and refractive indices (RI) of tissue are important
      parameters in tissue optics. These parameters can be determined from quantitative
      phase images of thin slices of tissue blocks. However, the changes in RI and
      structure of cells due to fixation and paraffin embedding might result in
      inaccuracies in the estimation of the scattering properties of tissue. In this
      study, three-dimensional RI distributions of cells were measured using digital
      holographic microtomography to obtain total scattering cross sections (TSCS) of
      the cells based on the first-order Born approximation. We investigated the slight
      loss of dry mass and drastic shrinkage of cells due to paraformaldehyde fixation
      and paraffin embedding removal processes. We propose a method to compensate for
      the correlated changes in volume and RI of cells. The results demonstrate that
      the TSCS of live cells can be estimated using restored cells. The percentage
      deviation of the TSCS between restored cells and live cells was only -8%.
      Spatially resolved RI and scattering coefficients of unprocessed oral epithelium
      ranged from 1.35 to 1.39 and from 100 to 450 cm-1, respectively, estimated from
      paraffinembedded oral epithelial tissue after restoration of RI and volume.

PMID- 25069008
TI  - Viscous optical clearing agent for in vivo optical imaging.
AB  - By allowing more photons to reach deeper tissue, the optical clearing agent (OCA)
      has gained increasing attention in various optical imaging modalities. However,
      commonly used OCAs have high fluidity, limiting their applications in in vivo
      studies with oblique, uneven, or moving surfaces. In this work, we reported an
      OCA with high viscosity. We measured the properties of this viscous OCA, and
      tested its successful performances in the imaging of a living animal's skin with
      two optical imaging modalities: photoacoustic microscopy and optical coherence
      tomography. Our results demonstrated that the viscous OCA has a great potential
      in the study of different turbid tissues using various optical imaging
      modalities.

PMID- 25069009
TI  - Interlaced photoacoustic and ultrasound imaging system with real-time
      coregistration for ovarian tissue characterization.
AB  - Coregistered ultrasound (US) and photoacoustic imaging are emerging techniques
      for mapping the echogenic anatomical structure of tissue and its corresponding
      optical absorption. We report a 128-channel imaging system with real-time
      coregistration of the two modalities, which provides up to 15 coregistered frames
      per second limited by the laser pulse repetition rate. In addition, the system
      integrates a compact transvaginal imaging probe with a custom-designed fiber
      optic assembly for in vivo detection and characterization of human ovarian
      tissue. We present the coregistered US and photoacoustic imaging system
      structure, the optimal design of the PC interfacing software, and the
      reconfigurable field programmable gate array operation and optimization. Phantom
      experiments of system lateral resolution and axial sensitivity evaluation,
      examples of the real-time scanning of a tumor-bearing mouse, and ex vivo human
      ovaries studies are demonstrated.

PMID- 25069010
TI  - Defect structures and ordering behaviours of diblock copolymers self-assembling
      on spherical substrates.
AB  - One of the main differences of ordered structures constrained on curved surfaces
      is the nature of topological defects. We here explore the defect structures and
      ordering behaviours of both lamellar and cylindrical phases of block copolymers
      confined on spherical substrates by the Landau-Brazovskii theory, which is
      numerically solved by a highly accurate spectral method with a spherical harmonic
      basis. For the cylindrical phase, isolated disclinations and scars are generated
      on the spherical substrates. The number of excess dislocations in a scar depends
      linearly on the sphere radius. The defect fraction characterizing the ordering
      dynamics decays exponentially. The scars are formed from the isolated
      disclinations via mini-scars. For the lamellar phase, three types of defect
      structures (hedgehog, spiral and quasi-baseball) are identified. The disclination
      annihilation is the primary ordering mechanism of the lamellar phase. 

PMID- 25069011
TI  - A naturalistic comparison of the effectiveness of methadone and two sublingual
      formulations of buprenorphine on maintenance treatment outcomes: findings from a
      retrospective multisite study.
AB  - OBJECTIVE: This study sought to compare the effectiveness of the 3 most commonly
      prescribed maintenance medications in the United States indicated for the
      treatment of opioid dependence in reducing illicit drug use and retaining
      patients in treatment. METHOD: Data were abstracted from electronic medical
      records for 3,233 patients admitted to 34 maintenance treatment facilities
      located throughout the United States during the period of July 1, 2012, through
      July 1, 2013. Patients were grouped into 1 of 3 medication categories based on
      their selection at intake (methadone [n = 2,738; M dosage = 64.64 mg/d, SD =
      25.58], Suboxone [n = 102; M dosage = 9.75 mg/d, SD = 4.04], or Subutex [n = 393;
      M dosage = 12.21 mg/d, SD = 5.31]) and were studied through retrospective chart
      review for 6 months or until treatment discharge. Two measures of patient
      retention in treatment and urinalysis drug screen (UDS) findings for both opioids
      and various nonopioid substances comprised the study outcomes. RESULTS: The
      average length of stay (LOS) in terms of days in treatment for the methadone
      group (M = 169.86, SE = 5.02) was significantly longer than both the Subutex (M =
      69.34, SE = 23.43) and Suboxone (M = 119.35, SE = 20.82) groups. The Suboxone
      group evinced a significantly longer average LOS relative to the Subutex group.
      After adjustment for relevant covariates, patients maintained on methadone were
      3.73 times (95% confidence interval [CI]= 2.82-4.92) and 2.48 times (95% CI =
      1.57-3.92) more likely to be retained in treatment at 6 months than patients
      prescribed Subutex and Suboxone, respectively. The 6-month prevalence rates of
      positive UDS findings for both opioids and nonopioid substances were similar
      across medication groups. CONCLUSIONS: Comparable rates of illicit drug use at 6
      months may be expected irrespective of maintenance medication, while increased
      retention may be expected for patients maintained on methadone relative to those
      maintained on Suboxone or Subutex.

PMID- 25069013
TI  - Effects of baclofen and naltrexone, alone and in combination, on the consumption
      of palatable food in male rats.
AB  - Excess consumption of palatable food has been shown to affect reward-related
      brain regions, and pharmaceutical treatments for drug addiction may also be
      effective in treating overeating of such foods. The GABA-B agonist baclofen and
      opioid antagonist naltrexone have both been used to treat addiction, and have
      been shown to suppress intake of certain foods. The combination of these drugs
      has shown to be more effective in reducing alcohol consumption than either drug
      alone. The present study assessed the effects of naltrexone and baclofen, alone
      and in combination, on intake of foods comprised of various macronutrients. Male
      Sprague-Dawley rats were given 12-hr daily access to chow and a fat emulsion,
      sugar-fat emulsion, or a sugar solution for 21 days. Rats were then administered
      (intraperitoneal) baclofen-naltrexone combinations (0.1 mg/kg naltrexone and 1.0
      mg/kg baclofen, 1.0 mg/kg naltrexone and 1.8 mg/kg baclofen), and naltrexone
      (0.1, 1.0 mg/kg) and baclofen (1.0, 1.8 mg/kg) alone. The high dose of the
      baclofen-naltrexone combination reduced palatable food intake in both the fat and
      sugar-fat groups compared with vehicle, without affecting chow consumption in
      these groups. Naltrexone showed little significant effects on intake of either
      palatable food or chow. Baclofen also reduced palatable food intake in the fat
      and fat-sugar groups, but differences were only noted between the low and high
      dose. The combination of baclofen and naltrexone may be a useful tool in
      selectively targeting the consumption of high-fat and sugar- and fat-rich foods.

PMID- 25069012
TI  - A new look at risk-taking: using a translational approach to examine risk-taking
      behavior on the balloon analogue risk task.
AB  - Models of risk-taking typically assume that the variability of outcomes is
      important in the likelihood of making a risky choice. In an animal model of the
      Balloon Analogue Risk Task (BART), within-session variability, or the coefficient
      of variability (CV), was found to be a novel predictor of behavior (Jentsch et
      al., 2010). Human studies have not investigated how BART performance differs when
      using the CV versus a traditional BART measure (e.g., number of pumps). This
      study sought to determine whether the CV provides a unique and valuable
      alternative index of risk-taking on the BART, and to determine the relationship
      of the CV to self-reported alcohol consumption. Young adult heavy drinkers (n =
      58, 72% male, mean age 21.53) completed an assessment of drinking patterns and a
      modified version of the BART. Multiple regression results indicated that CV is a
      unique predictor of total explosions and total money earned on the BART. Higher
      levels of variability were associated with fewer explosions but less money
      earned, whereas more pumps was associated with more explosions but more money.
      Higher CV was also associated with lower lifetime and past 3 months peak drinking
      quantity, higher levels of self-efficacy to control drinking, and lower levels of
      drinking acceptability (i.e., injunctive norms). Total pumps was associated with
      higher lifetime peak drinking, lower self-efficacy to control drinking, and
      higher levels drinking acceptability. Overall, the CV can provide an alternative
      method of assessing BART performance and the association of risk-taking with
      drinking patterns.

PMID- 25069014
TI  - Examining educational attainment, prepregnancy smoking rate, and delay
      discounting as predictors of spontaneous quitting among pregnant smokers.
AB  - We investigated three potential predictors (educational attainment, prepregnancy
      smoking rate, and delay discounting [DD]) of spontaneous quitting among pregnant
      smokers. These predictors were examined alone and in combination with other
      potential predictors using study-intake assessments from controlled clinical
      trials examining the efficacy of financial incentives for smoking cessation and
      relapse prevention. Data from 349 pregnant women (231 continuing smokers and 118
      spontaneous quitters) recruited from the greater Burlington, VT, area contributed
      to this secondary analysis, including psychiatric/sociodemographic
      characteristics, smoking characteristics, and performance on a computerized DD
      task. Educational attainment, smoking rate, and DD values were each significant
      predictors of spontaneous quitting in univariate analyses. A model examining
      those three predictors together retained educational attainment as a main effect
      and revealed a significant interaction of DD and smoking rate (i.e., DD was a
      significant predictor at lower but not higher smoking rates). A final model
      considering all potential predictors, included education, the interaction of DD
      and smoking rate, and five additional predictors (i.e., stress ratings, the
      belief that smoking during pregnancy will "greatly harm my baby," age of smoking
      initiation, marital status, and prior quit attempts during pregnancy). The study
      presented here contributes new knowledge on predictors of spontaneous quitting
      among pregnant smokers with substantive practical implications for reducing
      smoking during pregnancy.

PMID- 25069016
TI  - A rapid method to determine colonic microbial metabolites derived from grape
      flavanols in rat plasma by liquid chromatography-tandem mass spectrometry.
AB  - This study describes the development and validation of a liquid chromatography
      mass spectrometry method for determination of a large number of flavanol colonic
      derivatives in biological samples. The method was validated with rat plasma after
      the intake of grape seed flavanols. The minimum plasma volume necessary to
      maintain good recovery values within the range of 83-110% for all of the
      standards was determined by micro solid-phase extraction (MU-SPE). In total, 16
      commercial standards were used to measure 30 different phenolic compounds present
      at low concentration levels (micromolar). The chromatographic method enabled
      reliable quantification of plasma colonic flavanol derivatives with low limits of
      detection and quantification, achieving values of 0.03 nM and 0.10 nM,
      respectively. The developed method can be readily applied to determine all of the
      flavanol metabolites that are most likely responsible for the majority of
      biological effects of poorly absorbed flavanols. 

PMID- 25069015
TI  - 19F NMR indicator displacement assay using a synthetic receptor with appended
      paramagnetic relaxation agent.
AB  - An admixture of zinc(II)-bis(dipicolylamine) receptor with covalently attached
      paramagnetic relaxation agent and fluorine-labeled phosphate indicator enables
      (19)F NMR detection of phosphorylated analytes with amplified switched-on signal
      intensity.

PMID- 25069017
TI  - Serum free thyroxine concentration is associated with metabolic syndrome in
      euthyroid subjects.
AB  - CONTEXT: The association between thyroid hormones within the euthyroid range and
      metabolic syndrome is not clear. AIM: This study evaluated the relationship
      between thyroid hormones and metabolic syndrome and its components in euthyroid
      subjects. DESIGN AND SETTING: This is a cross-sectional population based study
      conducted within the framework of the cohort of the Tehran Thyroid Study.
      PARTICIPANTS: Out of 5786 subjects aged >= 20 years, 3755 euthyroid subjects
      without a history of thyroid disorders, diabetes, or use of steroids or lipid
      lowering agents were investigated. OUTCOME MEASURES: Body weight, waist
      circumference (WC), and blood pressure (BP) were measured. Serum concentrations
      of lipids and lipoproteins, fasting blood glucose (FBG), insulin, free T4 (FT4),
      and thyrotropin (TSH) were assayed. Metabolic syndrome was determined by
      definition of the Joint Interim Statement adjusted for the Iranian population.
      RESULTS: After adjustment for age, sex, and smoking, serum FT4 was significantly
      associated with high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), triglycerides (TGs), WC, systolic BP, and
      diastolic BP; the associations that remained significant after further adjustment
      for body mass index (BMI) and the homeostasis model assessment index for insulin
      resistance (HOMA-IR) except for HDL-C. Serum TSH was associated only with TGs
      after adjustments for age, sex, smoking, and BMI, an association that disappeared
      after further adjustment for HOMA-IR. Serum FT4 was negatively associated (beta=
      0.02, 95% confidence interval [CI: -0.03, -0.01]) and TSH was positively
      associated (beta = 0.03 [CI: 0.01, 0.04) with insulin resistance. The prevalence
      of metabolic syndrome decreased from 30.1% in the lowest FT4 tertile to 22.4% in
      the highest FT4 tertile (p<0.001). The prevalence of other metabolic syndrome
      components decreased significantly from higher to lower FT4 tertiles. Higher FT4
      values were associated with lower odds of metabolic syndrome (OR = 0.96 [95% CI:
      0.92, 0.99]; p=0.01). CONCLUSION: In euthyroid subjects, FT4, rather than TSH, is
      associated with risk of metabolic syndrome and its components.

PMID- 25069018
TI  - Protein engineering of selected residues from conserved sequence regions of a
      novel Anoxybacillus alpha-amylase.
AB  - The alpha-amylases from Anoxybacillus species (ASKA and ADTA), Bacillus aquimaris
      (BaqA) and Geobacillus thermoleovorans (GTA, Pizzo and GtamyII) were proposed as
      a novel group of the alpha-amylase family GH13. An ASKA yielding a high
      percentage of maltose upon its reaction on starch was chosen as a model to study
      the residues responsible for the biochemical properties. Four residues from
      conserved sequence regions (CSRs) were thus selected, and the mutants F113V (CSR
      I), Y187F and L189I (CSR-II) and A161D (CSR-V) were characterised. Few changes in
      the optimum reaction temperature and pH were observed for all mutants. Whereas
      the Y187F (t1/2 43 h) and L189I (t1/2 36 h) mutants had a lower thermostability
      at 65 degrees C than the native ASKA (t1/2 48 h), the mutants F113V and A161D
      exhibited an improved t1/2 of 51 h and 53 h, respectively. Among the mutants,
      only the A161D had a specific activity, k(cat) and k(cat)/K(m) higher (1.23-,
      1.17- and 2.88-times, respectively) than the values determined for the ASKA. The
      replacement of the Ala-161 in the CSR-V with an aspartic acid also caused a
      significant reduction in the ratio of maltose formed. This finding suggests the
      Ala-161 may contribute to the high maltose production of the ASKA.

PMID- 25069020
TI  - Kinetics of the coefficient of friction of elastomers.
AB  - We study theoretically and numerically the kinetics of the coefficient of
      friction of an elastomer due to abrupt changes of sliding velocity. Numerical
      simulations reveal the same qualitative behavior which has been observed
      experimentally on different classes of materials: the coefficient of friction
      first jumps and then relaxes to a new stationary value. The elastomer is modeled
      as a simple Kelvin body and the surface as a self-affine fractal with a Hurst
      exponent in the range from 0 to 1. Parameters of the jump of the coefficient of
      friction and the relaxation time are determined as functions of material and
      loading parameters. Depending on velocity and the Hurst exponent, relaxation of
      friction with characteristic length or characteristic time is observed. 

PMID- 25069019
TI  - Synthesis of novel derivatives of 4-methylbenzimidazole and evaluation of their
      biological activities.
AB  - 4-Methylbenzimidazole 1-28 novel derivatives were synthesized and evaluated for
      their antiglycation and antioxidant activities. Compounds 1-7 and 11 showed
      excellent activities ranged 140-280 MUM, better than standard drug rutin (294.46
      +/- 1.50 MUM). Compound 1-28 were also evaluated for DPPH activities. Compounds 1
      8 showed excellent activities, ranging 12-29 MUM, better than standard drug n
      propylgallate (IC50 = 30.30 +/- 0.40 MUM). For superoxide anion scavenging
      activity, compounds 1-7 showed better activity than standard n-propylgallate
      (IC50 = 106.34 +/- 1.6 MUM), ranged 82-104 MUM. These compounds were found to be
      nontoxic to THP-1 cells.

PMID- 25069021
TI  - Agave fructans: their effect on mineral absorption and bone mineral content.
AB  - In this study we investigate the effect that Agave fructans as new prebiotics
      have on mineral absorption improvement. Forty-eight 12-week-old C57BL/6J mice
      were used in this study. Forty mice were ovariectomized and eight were sham
      operated controls. Mice were fed standard diets or diets supplemented with 10%
      Agave fructans or 10% inulin fructans. Calcium and magnesium were evaluated as
      well as their excretion in feces. Osteocalcin levels were also measured; femur
      structure was studied by scanning electron microscopy. Other parameters, such as
      food intake, body weight, glucose, and short-chain fatty acid content, were
      recorded. Calcium in plasma and bone increased in Agave fructan groups (from 53.1
      to 56 and 85 mg/L and from 0.402 to 0.474 and 0.478 g/g, respectively) and
      osteocalcin increased in all fructan groups (>50%). Scanning electron microscopy
      showed that fructans were able to mitigate bone loss. In conclusion, we
      demonstrated that supplementation with Agave fructans prevents bone loss and
      improves bone formation.

PMID- 25069022
TI  - Emergency inventory management for disasters--a review.
AB  - There has been a recent surge in the publication of academic literature examining
      various aspects of emergency inventory management for disasters. This article
      contains a timely literature review of these studies, beginning with an
      exposition of the characteristics of storage and delivery options for emergency
      supplies, with a particular emphasis on the differences between emergency
      inventories and conventional inventory management. Using a novel classification
      scheme and a comprehensive search of the inventory related literature, an
      overview of the emergency inventory management studies is also presented.
      Finally, based on this extensive review, a discussion is presented based on the
      critical issues and key findings related to the emergency inventory management
      field, and include suggestions for future research directions.

PMID- 25069023
TI  - Simulation and optimization models for emergency medical systems planning.
AB  - The authors address strategic planning problems for emergency medical systems
      (EMS). In particular, the three following critical decisions are considered: i)
      how many ambulances to deploy in a given territory at any given point in time, to
      meet the forecasted demand, yielding an appropriate response time; ii) when
      ambulances should be used for serving nonurgent requests and when they should
      better be kept idle for possible incoming urgent requests; iii) how to define an
      optimal mix of contracts for renting ambulances from private associations to meet
      the forecasted demand at minimum cost. In particular, analytical models for
      decision support, based on queuing theory, discrete-event simulation, and integer
      linear programming were presented. Computational experiments have been done on
      real data from the city of Milan, Italy. 

PMID- 25069024
TI  - Stress and coping in wildland firefighting dispatchers.
AB  - OBJECTIVE: To gain a better understanding of the stressors faced by wildland
      firefighting dispatchers and how they cope with it. DESIGN: Qualitative method of
      phenomenology. SETTING: Dispatch centers around the western United States.
      SUBJECTS: Subjects were recruited via e-mail solicitation. Only currently
      employed wildland firefighting dispatchers with extensive dispatching experience
      were selected. Dispatchers included in this study were employed at the local (3),
      geographic (4), or national level (4). Eleven dispatchers in total were
      interviewed, six females and five males. Average experience level as a dispatcher
      was 14.2 years. INTERVENTIONS: In-person interviews. RESULTS: Three broad
      categories of stressors were revealed: balancing personal and professional lives,
      contending with job-related issues, and dealing with issues related to control.
      Four coping strategies also emerged: taking time off, exercising, providing a
      service to firefighters, and receiving support from others. CONCLUSIONS: In
      general, a complex and at times even a paradoxical relationship between the
      dispatchers interviewed and stress was noted. In other words, while subjects felt
      that the stressors experienced as a dispatcher had the ability to negatively
      affect their performance, they also believed that stress was beneficial at times.
      Future research is recommended to further our understanding of workplace
      stressors for wildland fire dispatchers, and how they cope with them.

PMID- 25069025
TI  - Assessing reverse 911(r): a case study of the 2007 San Diego wildfires.
AB  - In October 2007, 250,000 residents of San Diego County were forced to evacuate as
      wildfires burned 62 miles(2) in 24 hours. In 2005, the Sheriff's Department
      invested in Reverse 911(r) to contact residents upon emergencies. The system was
      used during this wildfire, and by the following midday, had made 394,915 calls.
      Shortly thereafter, 1,210 residents were surveyed to investigate the
      effectiveness of this technology. Findings reveal that 42 percent of respondents
      received their first warning from a Reverse 911(r) call while an additional 7
      percent received the same call, but not as their first warning, as compared to
      all other methods used.

PMID- 25069026
TI  - The role of information technology in emergency preparedness by local health
      departments: a literature review.
AB  - Ever since the terrorist attacks of 9/11, the federal government increased
      funding for emergency preparedness. However, the literature continues to document
      several areas of weaknesses in public health emergency management by local health
      departments (LHD). This literature review discusses the role of information
      technology (IT) for emergency preparedness by LHDs. The focus areas for this
      review include evaluating the strategic management of IT by LHD, evaluation of
      the adoption and implementation of IT in emergency management, and assessing
      LHD's capacity and capability for emergency preparedness. Findings reveal that
      LHDs face significant challenges in the utilization of IT for emergency
      preparedness purposes such as weak capacity and capabilities, lack of structured
      planning and program implementation, and limited resources. Implications from
      this review include the development of "best practices," increased funding for IT
      infrastructure, and the establishment of strategic management framework for IT
      initiatives. 

PMID- 25069027
TI  - Serum amyloid protein A concentration in cryopyrin-associated periodic syndromes
      patients treated with interleukin-1 beta antagonist.
AB  - OBJECTIVES: Cryopyrin-associated periodic syndromes (CAPS) are a group of
      chronic, relapsing autoinflammatory disorders which may be complicated by
      systemic AA amyloidosis. The aim of our study was to evaluate serum amyloid
      protein A (SAA) level in CAPS patients treated with Interleukin-1beta (IL-1beta)
      antagonist and to correlate its level with treatment response. METHODS: All
      patients of CAPS Italian Register treated with IL-1beta inhibitor were enrolled.
      SAA levels before starting therapy, and at last visit were evaluated. Patients
      were then divided in complete responders and partial responders. RESULTS: Twenty
      five patients were enrolled. SAA level before starting therapy was increased
      (median 118.5 mg/L, IQR 96.4-252.8; normal value <6.4 mg/L), while at last visit
      SAA was significantly reduced (median 4.3 mg/L, IQR 2.3-12.7) (p<0.001). However
      12 patients still presented SAA levels beyond normal range, 10/25 patients (40%)
      showed a complete response to treatment. Conversely, 15 patients presented only a
      partial response, of which 12 for increased SAA value and 3 for increased CRP
      value. Patients with partial response had SAA values significantly higher than
      patients with complete response (median 12.6 mg/L; IQR 8.3-20.0 vs. 2.7 mg/L; IQR
      1.6-4.1, p<0.001). CONCLUSIONS: Our results confirm the long term efficacy of
      anti IL-1beta treatment in CAPS and the decrease of SAA levels; however 48% of
      patients still presented SAA elevation despite treatment. The real risk of these
      patients in developing amyloidosis is not clear but the persistent increase of
      SAA needs a close follow-up.

PMID- 25069029
TI  - One-pot oxidation and rearrangement of propargylamines and in situ pyrazole
      synthesis.
AB  - Reported here are procedures for a one-pot oxidation and rearrangement of
      propargylamines to synthesize enaminones, with supporting mechanistic studies.
      Also reported are the extended one-pot syntheses of pyrazoles, including
      celecoxib and various heterocyclic compounds. 

PMID- 25069030
TI  - Antibodies against infliximab are associated with de novo development of
      antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab
      switchers with IBD.
AB  - BACKGROUND: A notable proportion of patients with inflammatory bowel disease
      (IBD) are switched from infliximab (IFX) to adalimumab (ADL). We investigated if
      immunogenicity of IFX influenced immunogenicity and clinical outcomes of later
      ADL therapy. METHODS: Single-center cohort study including all patients with IBD
      assessed for antibodies (Abs) against IFX or ADL. RESULTS: Anti-IFX Abs were
      evaluated in 187 patients treated with IFX as first line anti-TNF agent.
      Approximately, half (49%) were positive. Detected anti-IFX Abs had functional
      capacity as judged by a median IFX concentration below limit of detection
      (interquartile range, 0.0-0.0 MUg/mL) versus 3.8 MUg/mL (IQR, 1.3-7.9) in anti
      IFX Ab-negative patients, P < 0.0001; but did not cross-react with ADL. Anti-ADL
      Abs were assessed in 57 ADL-treated patients. Twelve (21%) tested positive.
      Patients with previous anti-IFX Ab development were significantly more prone to
      develop anti-ADL Abs (33%) than those without (0%): odds ratio estimated 11, P =
      0.04. The anti-ADL Abs were also functional because ADL was undetectable in all
      anti-ADL Ab-positive patients versus median 8.3 MUg/mL (IQR 5.0-11.0) in anti-ADL
      negative patients, P < 0.0001. The presence of anti-ADL Abs increased the risk of
      secondary ADL treatment failure with OR 28 (3-248), P < 0.001. ADL trough levels,
      irrespectively of anti-ADL Ab status, associated with efficacy of ADL maintenance
      therapy: AUC(ROC) 0.77 (0.62-0.93), P < 0.01. CONCLUSIONS: Switchers with anti
      IFX Abs are prone to develop de novo anti-ADL Abs, which may result in
      therapeutic failure. Assessment of ADL immunogenicity in anti-IFX Ab-positive
      switchers is required to ensure optimal interventions at inadequate treatment
      responses and to avoid inappropriate ADL intensification regimens.

PMID- 25069031
TI  - Chromosomal polymorphism in Rineloricaria lanceolata Gunther, 1868 (Loricariidae:
      Loricariinae) of the Paraguay basin (Mato Grosso do Sul, Brazil): evidence of
      fusions and their consequences in the population.
AB  - Rineloricaria is the most species-rich genus of the Loricariinae (armored
      catfish) with 65 valid species. However, the karyotype structure is known only
      for eight species in this group. This study provides cytogenetic data for
      Rineloricaria lanceolata collected from the upper Paraguay basin (Mato Grosso do
      Sul). The specimens revealed extensive chromosomal polymorphism constituting 10
      karyotypes, which differed in the diploid number (48 to 45 chromosomes) and
      fundamental number (FN) between 52 and 55. Three types of chromosome variants
      were observed: a medium-sized submetacentric, a large submetacentric, and a small
      acrocentric form. Internal telomere sequences were demonstrated by a telomeric
      (TTAGGG)n probe in submetacentric chromosome variants, suggesting Robertsonian
      and tandem fusions. Considering the karyotype 2n=48 (4m+2st+42a, FN=54) as the
      starting point for this polymorphism, these rearrangements contributed to the
      reduction in diploid number (48-45). Furthermore, a remarkable polymorphism of
      18S rDNA resulted in three nucleolus organizer region phenotypes (I, II, and III)
      with variable frequencies. Interestingly, this polymorphism has remained in the
      population through interbreeding between specimens, resulting in different viable
      combinations. The data obtained confirm that diversification/karyotype evolution
      in Rineloricaria was marked by numerous chromosomal rearrangements which appear
      to be well tolerated in the panmitic population.

PMID- 25069032
TI  - Scale effect on dropwise condensation on superhydrophobic surfaces.
AB  - Micro/nano (two-tier) structures are often employed to achieve
      superhydrophobicity. In condensation, utilizing such a surface is not necessarily
      advantageous because the macroscopically observed Cassie droplets are usually in
      fact partial Wenzel in condensation. The increase in contact angle through
      introducing microstructures on such two-tier roughened surfaces may result in an
      increase in droplet departure diameter and consequently deteriorate the
      performance. In the meantime, nanostructure roughened surfaces could potentially
      yield efficient shedding of liquid droplets, whereas microstructures roughened
      surfaces often lead to highly pinned Wenzel droplets. To attain efficient
      shedding of liquid droplets in condensation on a superhydrophobic surface, a Bond
      number (a dimensionless number for appraising dropwise condensation) and a solid
      liquid fraction smaller than 0.1 and 0.3, respectively, are suggested. 

PMID- 25069033
TI  - Changing access to mental health care and social support when people living with
      HIV/AIDS become service providers.
AB  - As people living with HIV/AIDS (PHAs) achieve more stable health, many have taken
      on active peer support and professional roles within AIDS service organizations.
      Although the increased engagement has been associated with many improved health
      outcomes, emerging program and research evidence have identified new challenges
      associated with such transition. This paper reports on the results of a
      qualitative interpretive study that explored the effect of this role transition
      on PHA service providers' access to mental health support and self care. A total
      of 27 PHA service providers of diverse ethno-racial backgrounds took part in the
      study. Results show that while role transition often improves access to financial
      and health-care benefits, it also leads to new stress from workload demands,
      emotional triggers from client's narratives, feeling of burnout from over
      immersion in HIV at both personal and professional levels, and diminished self
      care. Barriers to seeking support included: concerns regarding confidentiality;
      self-imposed and enacted stigma associated with accessing mental health services;
      and boundary issues resulting from changes in relationships with peers and other
      service providers. Evolving support mechanisms included: new formal and informal
      peer support networks amongst colleagues or other PHA service providers to
      address both personal and professional challenges, and having access to
      professional support offered through the workplace. The findings suggest the need
      for increased organizational recognition of HIV support work as a form of
      emotional labor that places complex demands on PHA service providers. Increased
      access to employer-provided mental health services, supportive workplace
      policies, and adequate job-specific training will contribute to reduced work
      related stress. Community level strategies that support expansion of social
      networks amongst PHA service providers would reduce isolation. Systemic policies
      to increase access to insurance benefits and enhance sector-wide job preparedness
      and post-employment support will sustain long-term and meaningful involvement of
      PHAs in service provision. 

PMID- 25069034
TI  - Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung
      cancer patients treated with platinum-based chemotherapy.
AB  - Genetic variants in DNA repair genes may play a role in the effectiveness of
      platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We analyzed 17
      SNPs in eight genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XRCC1 and XRCC2)
      involved in DNA repair mechanisms and its association with outcome in NSCLC. This
      prospective study included patients with stages III and IV treated with platinum
      based chemotherapy. All patients (n = 161) received cisplatin or carboplatin plus
      a third-generation drug. Additionally, stage IIIA and IIIB patients (n = 74)
      received concomitant or sequential radiotherapy. Germline polymorphisms were
      analyzed using the BioMark system in blood DNA samples. We found that in stage
      III patients, response was significantly associated with SNPs in ERCC1 and in
      ERCC3 genes, while radiotherapy-derived toxicity correlated with SNPs in the
      ERCC2 gene. In stage IV patients, response was associated with a genetic variant
      in the ERCC4 gene and survival with a SNP in the XRCC1 gene. The complexity of
      the DNA repair mechanisms along with the heterogeneity in the treatment of lung
      cancer could explain the role of multiple genes as putative biomarkers of patient
      outcome. 

PMID- 25069036
TI  - Metabolic therapy: a new paradigm for managing malignant brain cancer.
AB  - Little progress has been made in the long-term management of glioblastoma
      multiforme (GBM), considered among the most lethal of brain cancers. Cytotoxic
      chemotherapy, steroids, and high-dose radiation are generally used as the
      standard of care for GBM. These procedures can create a tumor microenvironment
      rich in glucose and glutamine. Glucose and glutamine are suggested to facilitate
      tumor progression. Recent evidence suggests that many GBMs are infected with
      cytomegalovirus, which could further enhance glucose and glutamine metabolism in
      the tumor cells. Emerging evidence also suggests that neoplastic
      macrophages/microglia, arising through possible fusion hybridization, can
      comprise an invasive cell subpopulation within GBM. Glucose and glutamine are
      major fuels for myeloid cells, as well as for the more rapidly proliferating
      cancer stem cells. Therapies that increase inflammation and energy metabolites in
      the GBM microenvironment can enhance tumor progression. In contrast to current
      GBM therapies, metabolic therapy is designed to target the metabolic malady
      common to all tumor cells (aerobic fermentation), while enhancing the health and
      vitality of normal brain cells and the entire body. The calorie restricted
      ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic
      metabolic therapy that also reduces fermentable fuels in the tumor
      microenvironment. Metabolic therapy, as an alternative to the standard of care,
      has the potential to improve outcome for patients with GBM and other malignant
      brain cancers. 

PMID- 25069035
TI  - Systemic DNA damage accumulation under in vivo tumor growth can be inhibited by
      the antioxidant Tempol.
AB  - Recently we found that mice bearing subcutaneous non-metastatic tumors exhibited
      elevated levels of two types of complex DNA damage, i.e., double-strand breaks
      and oxidatively-induced clustered DNA lesions in various tissues throughout the
      body, both adjacent to and distant from the tumor site. This DNA damage was
      dependent on CCL2, a cytokine involved in the recruitment and activation of
      macrophages, suggesting that this systemic DNA damage was mediated via tumor
      induced chronic inflammatory responses involving cytokines, activation of
      macrophages, and consequent free radical production. If free radicals are
      involved, then a diet containing an antioxidant may decrease the distant DNA
      damage. Here we repeated our standard protocol in cohorts of two syngeneic tumor
      bearing C57BL/6NCr mice that were on a Tempol-supplemented diet. We show that
      double-strand break and oxidatively-induced clustered DNA lesion levels were
      considerably decreased, about two- to three fold, in the majority of tissues
      studied from the tumor-bearing mice fed the antioxidant Tempol compared to the
      control tumor-bearing mice. Similar results were also observed in nude mice
      suggesting that the Tempol effects are independent of functioning adaptive
      immunity. This is the first in vivo study demonstrating the effect of a dietary
      antioxidant on abscopal DNA damage in tissues distant from a localized source of
      genotoxic stress. These findings may be important for understanding the
      mechanisms of genomic instability and carcinogenesis caused by chronic stress
      induced systemic DNA damage and for developing preventative strategies. 

PMID- 25069037
TI  - FOXC2 promotes colorectal cancer proliferation through inhibition of FOXO3a and
      activation of MAPK and AKT signaling pathways.
AB  - Abnormal expression of FOXC2 has been found in several human cancers. However,
      the role of FOXC2 in the progression of colorectal cancer (CRC) has not been well
      characterized. In analysis of 206 CRC specimens, we revealed that both high
      expression and nuclear localization of FOXC2 were correlated to aggressive
      characteristics and poor survival of patients with CRC. FOXC2 promoted cell
      proliferation through activation of MAPK and AKT pathways, subsequently down
      regulating p27, up-regulating cyclin D1 and p-FOXO3a. Furthermore, FOXC2 nuclear
      localization was required for its promotion of cell proliferation. These findings
      suggest that FOXC2 plays an essential role in CRC progression and may serve as a
      valuable clinical prognostic marker of this disease. 

PMID- 25069038
TI  - Metronomic cyclophosphamide schedule-dependence of innate immune cell recruitment
      and tumor regression in an implanted glioma model.
AB  - Metronomic cyclophosphamide (CPA) treatment activates robust innate anti-tumor
      immunity and induces major regression of large, implanted brain tumor xenografts
      when administered on an intermittent, every 6-day schedule, but not on a daily
      low-dose or a maximum-tolerated dose CPA schedule. Here, we used an implanted
      GL261 glioma model to compare five intermittent metronomic CPA schedules to
      elucidate the kinetics and schedule dependence of innate immune cell recruitment
      and tumor regression. Tumor-recruited natural killer cells induced by two every 6
      day treatment cycles were significantly ablated 1 day after a third CPA
      treatment, but largely recovered several days later. Natural killer and other
      tumor-infiltrating innate immune cells peaked 12 days after the last CPA
      treatment on the every 6-day schedule, suggesting that drug-free intervals longer
      than 6 days may show increased efficacy. Metronomic CPA treatments spaced 9 or 12
      days apart, or on an alternating 6 and 9 day schedule, induced extensive tumor
      regression, similar to the 6-day schedule; however, the tumor-infiltrating
      natural killer cell responses were not sustained, leading to rapid resumption of
      tumor growth after day 24, despite ongoing metronomic CPA treatment. Increasing
      the CPA dose prolonged the period of tumor regression on the every 9-day
      schedule, but natural killer cell activation was markedly decreased. Thus, while
      several intermittent metronomic CPA treatment schedules can activate innate
      immune cell recruitment leading to major tumor regression, sustained immune and
      anti-tumor responses are only achieved on the 6-day schedule. However, even with
      this schedule, some tumors eventually relapse, indicating a need for further
      improvements in this immunogenic metronomic therapy. 

PMID- 25069040
TI  - The role of oxidized ATM in the regulation of oxidative stress-induced energy
      metabolism reprogramming of CAFs.
AB  - Cancer-associated fibroblasts (CAFs) are the predominant cell type in tumor
      microenvironment (TM) and featured with the distinct energy metabolism
      reprogramming (EMR) phenotype caused by many factors such as hypoxia and growth
      factors. The EMR of CAFs plays a key role in biological behaviors of cancer cells
      including proliferation, migration, invasion, and epithelial-mesenchymal
      transition (EMT). Recently, accumulative evidence indicates that oxidative stress
      (OS) mediates the EMR of CAFs under conditions of various stimuli. However, the
      precise mechanism by which OS causes the EMR of CAFs is not clear. Interestingly,
      our previous work suggested that ataxia-telangiectasia mutated (ATM) signaling is
      activated independent of DNA double strand breaks (DSBs) in CAFs derived from
      human breast cancers compared with paired normal fibroblasts (NFs). Recent
      studies have shown that ATM protein kinase, as a redox sensor, is closely
      associated with cellular energy metabolism. Thus, it is very possible that ATM
      protein kinase regulates the EMR of CAFs. So, it is necessary to perform an
      integral study on how oxidized ATM regulates the EMR of CAFs in response to
      various stimuli evoking OS. This will facilitate to develop a new powerful
      strategy of preventing and treating cancers. 

PMID- 25069041
TI  - Improving hematite-based photoelectrochemical water splitting with ultrathin TiO2
      by atomic layer deposition.
AB  - Ultrathin TiO2 was grown on hematite surface by atomic layer deposition (ALD).
      Obvious photoelectrochemical water oxidation performance improvement was observed
      for samples treated with as few as a single cycle of TiO2 deposition. Up to 100
      mV cathodic shift of the turn on potential was measured on samples treated by 20
      cycle ALD TiO2. Photocurrent improvement was also measured on samples treated by
      ALD TiO2. Systematic studies ruled out possibilities that the improvement was due
      to electrocatalytic or bulk doping effects. It was shown that the surface
      treatment led to better charge separation, less surface charge recombination and,
      hence, greater photovoltage by hematite. The facile surface treatment by
      ultrathin TiO2 may find broad applications in the development of stable and high
      performance photoelectrodes. 

PMID- 25069039
TI  - Critical roles for nitric oxide and ERK in the completion of prosurvival
      autophagy in 4OHTAM-treated estrogen receptor-positive breast cancer cells.
AB  - Autophagy is a mechanism of tamoxifen (TAM) resistance in ER-positive (ER+)
      breast cancer cells. In this study, we showed in ER+ MCF7 cells that 4
      hydroxytamoxifen (4OHTAM) induced cellular nitric oxide (NO) that negatively
      regulates cellular superoxide (O2-) and cytotoxicity. 4OHTAM stimulated LC3
      lipidation and formation of monodansylcadaverine (MDC)-labeled autophagic
      vesicles dependent on O2-. Depletion of NO increased O2- and LC3 lipidation, yet
      reduced formation of MDC-labeled autophagic vesicles. Instead, NO-depleted cells
      formed remarkably large vacuoles with rims decorated by LC3. The vacuoles were
      not labeled by MDC or the acidic lysosome-specific fluorescence dye acridine
      orange (AO). The vacuoles were increased by the late stage autophagy inhibitor
      chloroquine, which also increased LC3 lipidation. These results suggest NO is
      required for proper autophagic vesicle formation or maturation at a step after
      LC3 lipidation. In addition, 4OHTAM induced O2--dependent activation of ERK,
      inhibition of which destabilized lysosomes/autolysosomes upon 4OHTAM treatment
      and together with depletion of NO led to necrotic cell death. These results
      suggest an essential role for endogenous NO and ERK activation in the completion
      of pro-survival autophagy. 

PMID- 25069042
TI  - Electrical transport properties of single-layer WS2.
AB  - We report on the fabrication of field-effect transistors based on single layers
      and bilayers of the semiconductor WS2 and the investigation of their electronic
      transport properties. We find that the doping level strongly depends on the
      device environment and that long in situ annealing drastically improves the
      contact transparency, allowing four-terminal measurements to be performed and the
      pristine properties of the material to be recovered. Our devices show n-type
      behavior with a high room-temperature on/off current ratio of ~10(6). They show
      clear metallic behavior at high charge carrier densities and mobilities as high
      as ~140 cm(2)/(V s) at low temperatures (above 300 cm(2)/(V s) in the case of
      bilayers). In the insulating regime, the devices exhibit variable-range hopping,
      with a localization length of about 2 nm that starts to increase as the Fermi
      level enters the conduction band. The promising electronic properties of WS2,
      comparable to those of single-layer MoS2 and WSe2, together with its strong spin
      orbit coupling, make it interesting for future applications in electronic,
      optical, and valleytronic devices. 

PMID- 25069043
TI  - What is "community health"? Examining the meaning of an evolving field in public
      health.
AB  - In this commentary, we review definition frameworks for community health and
      examine factors having core relevance to shaping the meaning of this term and
      growing field. We conclude by suggesting a potential framework for
      conceptualizing and advancing this field of public health practice through
      improved understanding of the meaning, scope, and science of community health. 

PMID- 25069044
TI  - Investigation of the effect of telmisartan on experimentally induced peripheral
      nerve injury in rats.
AB  - AIM: The aim of this study was to investigate the effects of telmisartan on nerve
      healing in a rat peripheral nerve injury model. MATERIAL AND METHOD: Thirty adult
      male Wistar albino rats were divided into five groups: healthy, axonotmesis,
      anastomosis, axonotmesis+10 mg/kg telmisartan and anastomosis+10 mg/kg
      telmisartan. Walking track analyses were performed 4 weeks after the surgery. The
      right sciatic nerves of all the animals were examined histopathologically,
      stereologically and molecularly. RESULTS: Many badly damaged axons were detected
      in the axonotmesis group, in addition to enlarged spaces between the axons. In
      the anastomosis group, both ir- regular and degenerated axons at different
      severities were observed. The sections of the telmisartan group after the
      axonotmesis were similar to those of the healthy group. The sections of the
      telmisartan group after the anastomosis were similar to those of the healthy
      group and the telmisartan group after the axonotmesis. Interleukin-1 beta (IL
      1beta) gene expression increased in both the axonotmesis and the anastomosis
      groups when compared with the healthy group. Telmisartan had a significant down
      regulatory effect on IL-1beta expression. Caspase-3 mRNA expression was
      significantly increased in the anastomosis group, and the administration of
      telmisartan in this group significantly decreased this rise in caspase-3 mRNA
      expression. As a functional outcome, telmisartan also increased the walking
      distance of the rats after axonotmesis and anastomosis. CONCLUSION: The
      histopathological, stereological, functional and molecular data suggest that
      telmisartan improves nerve regeneration in peripheral nerve injuries by
      inhibiting inflammatory cytokine IL-1beta and apoptotic caspase-3.

PMID- 25069045
TI  - The genome and linkage map of the northern pike (Esox lucius): conserved synteny
      revealed between the salmonid sister group and the Neoteleostei.
AB  - The northern pike is the most frequently studied member of the Esociformes, the
      closest order to the diverse and economically important Salmoniformes. The
      ancestor of all salmonids purportedly experienced a whole-genome duplication
      (WGD) event, making salmonid species ideal for studying the early impacts of
      genome duplication while complicating their use in wider analyses of teleost
      evolution. Studies suggest that the Esociformes diverged from the salmonid
      lineage prior to the WGD, supporting the use of northern pike as a pre
      duplication outgroup. Here we present the first genome assembly, reference
      transcriptome and linkage map for northern pike, and evaluate the suitability of
      this species to provide a representative pre-duplication genome for future
      studies of salmonid and teleost evolution. The northern pike genome sequence is
      composed of 94,267 contigs (N50 = 16,909 bp) contained in 5,688 scaffolds (N50 =
      700,535 bp); the total scaffolded genome size is 878 million bases. Multiple
      lines of evidence suggest that over 96% of the protein-coding genome is present
      in the genome assembly. The reference transcriptome was constructed from 13
      tissues and contains 38,696 transcripts, which are accompanied by normalized
      expression data in all tissues. Gene-prediction analysis produced a total of
      19,601 northern pike-specific gene models. The first-generation linkage map
      identifies 25 linkage groups, in agreement with northern pike's diploid karyotype
      of 2N = 50, and facilitates the placement of 46% of assembled bases onto linkage
      groups. Analyses reveal a high degree of conserved synteny between northern pike
      and other model teleost genomes. While conservation of gene order is limited to
      smaller syntenic blocks, the wider conservation of genome organization implies
      the northern pike exhibits a suitable approximation of a non-duplicated
      Protacanthopterygiian genome. This dataset will facilitate future studies of
      esocid biology and empower ongoing examinations of the Atlantic salmon and
      rainbow trout genomes by facilitating their comparison with other major teleost
      groups.

PMID- 25069047
TI  - The mechanisms of Fenretinide-mediated anti-cancer activity and prevention of
      obesity and type-2 diabetes.
AB  - Fenretinide remains the most investigated retinoid compound for the prevention of
      cancer. Its clinical use remains a genuine possibility due to a favourable
      toxicological profile and accumulation in fatty tissues. Like other well
      characterised pharmacological therapies, Fenretinide has been shown to affect
      multiple signalling pathways. Recent findings have discovered additional
      beneficial properties the synthetic retinoid was not intentionally designed for,
      including the prevention of high-fat diet-induced obesity and insulin resistance.
      These preclinical findings in rodents are timely since obesity has reached
      pandemic proportions and safe effective therapeutics are severely lacking. Recent
      investigations have proposed various mechanisms of action for the beneficial
      effects of Fenretinide. This review covers the current knowledge about
      Fenretinide's use as a therapy for cancer and potential to treat obesity, insulin
      resistance and glucose intolerance. An overview of the signalling pathways
      manipulated by Fenretinide including retinoid homeostasis, reactive oxygen
      species generation and inhibition of ceramide synthesis will be presented and
      insights into apoptosis and/or autophagy induction by Fenretinide will also be
      discussed. The largely unexplored area of Fenretinide metabolites as alternative
      therapeutic options and how these may be relevant will also be presented.
      Fenretinide shows great promise, but unfortunately evidence is lacking from
      clinical trials on Fenretinide's effectiveness in humans. Finally we identify
      what action can be taken to further progress the investigation of this extremely
      important retinoid. 

PMID- 25069048
TI  - The pleiotropic profile of the indirubin derivative 6BIO overcomes TRAIL
      resistance in cancer.
AB  - TRAIL (TNFalpha-related apoptosis-inducing factor) has been promoted as a
      promising anti-cancer agent. Unfortunately many tumor cells develop resistance
      towards TRAIL due to numerous defects in apoptotic signaling. To handle this
      problem combination therapy with compounds affecting as many different anti
      apoptotic targets as possible might be a feasible approach. The bromo-substituted
      indirubin derivative 6BIO meets this challenge: Treatment of breast cancer and
      bladder carcinoma cell lines with micromolar concentrations of 6BIO abrogates
      cellular growth and induces apoptosis. Combination of subtoxic amounts of 6BIO
      with ineffective doses of TRAIL completely abolishes proliferation and long-term
      survival of cancer cells. As shown in two-dimensional as well as three
      dimensional cell culture models, 6BIO potently augments TRAIL-induced apoptosis
      in cancer cell lines. The potent chemosensitizing effect of 6BIO to TRAIL
      mediated cell death is due to the pleiotropic inhibitory profile of 6BIO. As
      shown previously, 6BIO abrogates STAT3, PDK1 as well as GSK3 signaling and
      moreover, inhibits the expression of the anti-apoptotic Bcl-2 family members Bcl
      xL and Mcl-1 on mRNA as well as on protein level, as demonstrated in this study.
      Moreover, the expression of cFLIP and cIAP1 is significantly downregulated in
      6BIO treated cancer cell lines. In sum (subtoxic concentration of) the multi
      kinase inhibitor 6BIO serves as a potent chemosensitizing agent fighting TRAIL
      resistant cancer cells. 

PMID- 25069046
TI  - Neuroimaging paradigms for tonotopic mapping (I): the influence of sound stimulus
      type.
AB  - Although a consensus is emerging in the literature regarding the tonotopic
      organisation of auditory cortex in humans, previous studies employed a vast array
      of different neuroimaging protocols. In the present functional magnetic resonance
      imaging (fMRI) study, we made a systematic comparison between stimulus protocols
      involving jittered tone sequences with either a narrowband, broadband, or sweep
      character in order to evaluate their suitability for the purpose of tonotopic
      mapping. Data-driven analysis techniques were used to identify cortical maps
      related to sound-evoked activation and tonotopic frequency tuning. Principal
      component analysis (PCA) was used to extract the dominant response patterns in
      each of the three protocols separately, and generalised canonical correlation
      analysis (CCA) to assess the commonalities between protocols. Generally speaking,
      all three types of stimuli evoked similarly distributed response patterns and
      resulted in qualitatively similar tonotopic maps. However, quantitatively, we
      found that broadband stimuli are most efficient at evoking responses in auditory
      cortex, whereas narrowband and sweep stimuli offer the best sensitivity to
      differences in frequency tuning. Based on these results, we make several
      recommendations regarding optimal stimulus protocols, and conclude that an
      experimental design based on narrowband stimuli provides the best sensitivity to
      frequency-dependent responses to determine tonotopic maps. We forward that the
      resulting protocol is suitable to act as a localiser of tonotopic cortical fields
      in individuals, or to make quantitative comparisons between maps in dedicated
      tonotopic mapping studies. 

PMID- 25069049
TI  - Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells
      via upregulation of ICAM-1.
AB  - Cannabinoids have been shown to promote the expression of the intercellular
      adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive
      and antimetastatic action. Using lung cancer cell lines (A549, H460) and
      metastatic cells derived from a lung cancer patient, the present study addressed
      the impact of cannabinoid-induced ICAM-1 on cancer cell adhesion to lymphokine
      activated killer (LAK) cells and LAK cell-mediated cytotoxicity. Cannabidiol
      (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer
      cells to adhere to and subsequently be lysed by LAK cells, with both effects
      being reversed by a neutralizing ICAM-1 antibody. Increased cancer cell lysis by
      CBD was likewise abrogated when CBD-induced ICAM-1 expression was blocked by
      specific siRNA or by antagonists to cannabinoid receptors (CB1, CB2) and to
      transient receptor potential vanilloid 1. In addition, enhanced killing of CBD
      treated cancer cells was reversed by preincubation of LAK cells with an antibody
      to lymphocyte function associated antigen-1 (LFA-1) suggesting intercellular ICAM
      1/LFA-1 crosslink as crucial event within this process. ICAM-1-dependent pro
      killing effects were further confirmed for the phytocannabinoid Delta(9)
      tetrahydrocannabinol (THC) and R(+)-methanandamide (MA), a hydrolysis-stable
      endocannabinoid analogue. Finally, each cannabinoid elicited no significant
      increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS
      2B, associated with a far less pronounced (CBD, THC) or absent (MA) ICAM-1
      induction as compared to cancer cells. Altogether, our data demonstrate
      cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible
      for increased cancer cell lysis by LAK cells. These findings provide proof for a
      novel antitumorigenic mechanism of cannabinoids. 

PMID- 25069050
TI  - Facile preparation of super durable superhydrophobic materials.
AB  - The low stability, complicated and expensive fabrication procedures seriously
      hinder practical applications of superhydrophobic materials. Here we report an
      extremely simple method for preparing super durable superhydrophobic materials,
      e.g., textiles and sponges, by dip coating in fluoropolymers (FPs). The
      morphology, surface chemical composition, mechanical, chemical and environmental
      stabilities of the superhydrophobic textiles were investigated. The results show
      how simple the preparation of super durable superhydrophobic textiles can be! The
      superhydrophobic textiles outperform their natural counterparts and most of the
      state-of-the-art synthetic superhydrophobic materials in stability. The intensive
      mechanical abrasion, long time immersion in various liquids and repeated washing
      have no obvious influence on the superhydrophobicity. Water drops are spherical
      in shape on the samples and could easily roll off after these harsh stability
      tests. In addition, this simple dip coating approach is applicable to various
      synthetic and natural textiles and can be easily scaled up. Furthermore, the
      results prove that a two-tier roughness is helpful but not essential with regard
      to the creation of super durable superhydrophobic textiles. The combination of
      microscale roughness of textiles and materials with very low surface tension is
      enough to form super durable superhydrophobic textiles. According to the same
      procedure, superhydrophobic polyurethane sponges can be prepared, which show high
      oil absorbency, oil/water separation efficiency and stability. 

PMID- 25069051
TI  - Relations between inhibitory control and the development of academic skills in
      preschool and kindergarten: a meta-analysis.
AB  - Although there is evidence that young children's inhibitory control (IC) is
      related to their academic skills, the nature of this relation and the role of
      potential moderators of it are not well understood. In this meta-analytic study,
      we summarized results from 75 peer-reviewed studies of preschool and kindergarten
      children (14,424 children; 32-80 months old [M = 54.71 months; SD = 9.70]) across
      a wide range of socioeconomic status. The mean effect size (r) across studies was
      .27 (95% confidence interval [.24, .29]), indicating a moderate and statistically
      significant association between self-regulation and academic skills. The
      association between IC and academic skills was moderated by type of IC behavior
      task (i.e., hot vs. cool behavior task), by method of assessing IC (i.e.,
      behavior task vs. parent report), and by academic subject (i.e., literacy vs.
      math), but not by other methods of assessing IC (i.e., behavior task vs. teacher
      report, parent report vs. teacher report) or by grade (i.e., preschool vs.
      kindergarten). The results of this meta-analysis suggest that there are preferred
      methods for assessing IC (i.e., cool behavior tasks, teacher reports) that should
      be considered when examining the relations between IC and academic skills in
      young children. (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 25069052
TI  - Development of attention networks and their interactions in childhood.
AB  - In the present study, we investigated developmental trajectories of alerting,
      orienting, and executive attention networks and their interactions over
      childhood. Two cross-sectional experiments were conducted with different samples
      of 6- to 12-year-old children using modified versions of the attention network
      task (ANT). In Experiment 1 (N = 106), alerting and orienting cues were
      independently manipulated, thus allowing examination of interactions between
      these 2 networks, as well as between them and the executive attention network. In
      Experiment 2 (N = 159), additional changes were made to the task in order to
      foster exogenous orienting cues. Results from both studies consistently revealed
      separate developmental trajectories for each attention network. Children younger
      than 7 years exhibited stronger benefits from having an alerting auditory signal
      prior to the target presentation. Developmental changes in orienting were mostly
      observed on response accuracy between middle and late childhood, whereas
      executive attention showed increases in efficiency between 7 years and older
      ages, and further improvements in late childhood. Of importance, across both
      experiments, significant interactions between alerting and orienting, as well as
      between each of these and the executive attention network, were observed.
      Alerting cues led to speeding shifts of attention and enhancing orienting
      processes. Also, both alerting and orienting cues modulated the magnitude of the
      flanker interference effect. These findings inform current theoretical models of
      human attention and its development, characterizing for the first time, the age
      related course of attention networks interactions that, present in adults, stem
      from further refinements over childhood.

PMID- 25069053
TI  - An observational study of co-rumination in adolescent friendships.
AB  - Co-rumination is a dyadic process between relationship partners that refers to
      excessively discussing problems, rehashing problems, speculating about problems,
      mutual encouragement of problem talk, and dwelling on negative affect. Although
      studies have addressed youths' tendency to co-ruminate, little is known about the
      nature of co-ruminative conversations. The primary goal of the present study (N =
      314 adolescent friend dyads) was to identify microsocial processes that sustain
      and reinforce problem talk among adolescent co-ruminating friends. Results
      indicated that co-rumination was characterized by friends responding to each
      other's statements about problems with engaged statements (e.g., questions,
      supportive statements) that elicited even more problem talk. Results also
      indicated that some aspects of co-rumination (i.e., extensively talking about
      problems, rehashing problems, speculating about problems, and mutual
      encouragement of problem talk) were associated with positive friendship
      adjustment, whereas other aspects (i.e., dwelling on negative affect) were
      associated with internalizing problems. The present research highlights the
      utility of attending to microsocial processes in friends' conversations and has
      implications for intervention.

PMID- 25069055
TI  - Age, psychological maturity, and the transition to motherhood among English
      speaking Australian women in a metropolitan area.
AB  - In the context of the trend toward delayed parenthood, this study examines
      whether older maternal age is associated with greater psychological maturity and
      whether greater psychological maturity provides any adaptive benefit during the
      transition to motherhood. A sample of 240 predominantly English-speaking
      Australian women in a metropolitan area expecting their 1st baby (mean age =
      32.81 years; 41% conceived after fertility treatment) completed measures of
      psychological maturity (hardiness, ego development, and ego resiliency) and
      pregnancy adaptation (maternal fetal attachment and formation of a maternal
      identity) in the 3rd trimester of pregnancy and a measure of postnatal adjustment
      at 4-6 months postpartum. Structural equation modeling showed age was positively
      associated with a latent construct of psychological maturity, and psychological
      maturity was associated with more optimal adaptation in pregnancy and early
      motherhood. Both psychological maturity and pregnancy adaptation predicted
      positive postnatal adjustment. Age was indirectly related to adaptation through
      its relationship with psychological maturity. The relationships in the model
      applied regardless of mode of conception (fertility treatment or spontaneous).
      Potentially confounding contextual factors associated with older age at
      motherhood, higher education, and maternal and child health were included in the
      model. These results suggest that psychological maturity is a benefit of
      motherhood at older ages.

PMID- 25069054
TI  - Age-related sex differences in language lateralization: A magnetoencephalography
      study in children.
AB  - It is well supported by behavioral and neuroimaging studies that typical language
      function is lateralized to the left hemisphere in the adult brain and this
      laterality is less well defined in children. The behavioral literature suggests
      there maybe be sex differences in language development, but this has not been
      examined systematically with neuroimaging. In this study, magnetoencephalography
      was used to investigate the spatiotemporal patterns of language lateralization as
      a function of age and sex. Eighty typically developing children (46 female, 34
      male; 4-18 years) participated in an overt visual verb generation task. An
      analysis method called differential beamforming was used to analyze language
      related changes in oscillatory activity referred to as low-gamma event-related
      desynchrony (ERD). The proportion of ERD over language areas relative to total
      ERD was calculated. We found different patterns of laterality between boys and
      girls. Boys showed left-hemisphere lateralization in the frontal and temporal
      language-related areas across age groups, whereas girls showed a more bilateral
      pattern, particularly in frontal language-related areas. Differences in patterns
      of ERD were most striking between boys and girls in the younger age groups, and
      these patterns became more similar with increasing age, specifically in the
      preteen years. Our findings show sex differences in language lateralization
      during childhood; however, these differences do not seem to persist into
      adulthood. We present possible explanations for these differences. We also
      discuss the implications of these findings for presurgical language mapping in
      children and highlight the importance of examining the question of sex-related
      language differences across development.

PMID- 25069056
TI  - Liquid chromatography-bioassay-mass spectrometry for profiling of physiologically
      active food.
AB  - Complex samples like food contain thousands of single compounds. In the past,
      only known target compounds were looked for; however, most bioactive compounds in
      food are unknown. On the contrary, nontarget analyses face the challenge of
      determining the thousand peaks' identities, but it remains largely unclear which
      peaks are bioactive. Here, we show a novel effect-directed food profiling, as
      food and food supplements can be unknowingly physiologically active. By the
      combination of planar chromatography, using water-wettable reversed phase high
      performance thin-layer chromatography (HPTLC RP18 W) plates, with detection by
      specific microorganisms, endocrine compounds in food were quantitatively detected
      as sharp-bounded zones and further characterized by mass spectrometry. This
      analytical workflow allowed frequent food intakes to be identified as risky with
      regard to estrogen-effective compounds, in discussion for their potential
      involvement in foodborne pathogenesis and for use in personalized health care.
      Using this accelerated workflow with its comprehensive detection potential,
      unknown endocrine compounds can be discovered. Exemplarily, the discovery of up
      to six endocrine disrupting compounds was shown in seven propolis samples and in
      four spices. For example, microorganisms quantitatively detected an estrogen
      effective compound in the range of 0.07-0.24% in seven propolis samples, which
      was assigned to be caffeic acid phenethyl ester by mass spectrometry. This
      streamlined nontarget analysis detected modes of action, followed by targeted
      characterization of newly discovered effective compounds. Also, drug discovery or
      analysis of traditional medicines may profit from this effect-directed profiling
      of complex samples. 

PMID- 25069057
TI  - Are patients with diabetes mellitus satisfied with technologies used to assist
      with diabetes management and coping?: A structured review.
AB  - Modern technological devices supporting coping and management for patients with
      diabetes are increasingly popular and could be important healthcare tools. This
      review aimed to evaluate patient satisfaction and perceptions regarding these
      devices, examples of which include short message service reminder systems, online
      educational programs, and clinician-patient electronic communication. Therapy
      devices such as continuous glucose monitors and continuous subcutaneous insulin
      infusion pumps are not included in this review. Embase, Psychinfo, Medline,
      CINAHL, and gray literature databases were searched for "diabetes mellitus,"
      "technical device," "patient satisfaction," and their synonyms. This review was
      carried out according to the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses statement guidelines. The search produced 1,902 studies, 26 of
      which were included in the review: type 1 diabetes mellitus (eight studies), type
      2 diabetes mellitus (nine studies), and both (nine studies). High satisfaction
      was seen with almost all devices and correlated strongly with ease of use and
      improved diabetes management. Satisfaction was not affected by participant age,
      and the effect of diabetes type was not assessed. Web devices were reported as
      easiest to use. Increased support was valued and resulted from devices
      facilitating interaction with healthcare professionals (HCPs) or peers. Technical
      difficulties were barriers to both use and satisfaction. Overall, patients
      enjoyed supplementing their usual therapy with these devices. Perceived support
      from HCPs or peers formed an important aspect of patient satisfaction and should
      be considered for future interventions.

PMID- 25069058
TI  - Nostosins, Trypsin Inhibitors Isolated from the Terrestrial Cyanobacterium Nostoc
      sp. Strain FSN.
AB  - Two new trypsin inhibitors, nostosin A (1) and B (2), were isolated from a
      hydrophilic extract of Nostoc sp. strain FSN, which was collected from a paddy
      field in the Golestan Province of Iran. Nostosins A (1) and B (2) are composed of
      three subunits, 2-hydroxy-4-(4-hydroxyphenyl)butanoic acid (Hhpba), L-Ile, and L
      argininal (1) or argininol (2). Nostosins A (1) and B (2) exhibited IC50 values
      of 0.35 and 55 MUM against porcine trypsin, respectively, suggesting that the
      argininal aldehyde group plays a crucial role in the efficient inhibition of
      trypsin. Molecular docking of nostosin A (1) (449 Da), leupeptin (426 Da, IC50
      0.5 MUM), and spumigin E (610 Da, IC50 < 0.1 MUM) with trypsin suggested
      prominent binding similarity between nostosin A (1) and leupeptin but only
      partial binding similarity with spumigin E. The number of hydrogen bonds between
      ligands and trypsin increased according to the length and size of the ligand
      molecule, and the docking affinity values followed the measured IC50 values.
      Nostosin A (1) is the first highly potent three-subunit trypsin inhibitor with
      potency comparable to the known commercial trypsin inhibitor leupeptin. These
      findings expand the known diversity of short-chain linear peptide protease
      inhibitors produced by cyanobacteria.

PMID- 25069059
TI  - Analysis of the kinetics and yields of OH radical production from the CH3OCH2 +
      O2 reaction in the temperature range 195-650 K: an experimental and computational
      study.
AB  - The methoxymethyl radical, CH3OCH2, is an important intermediate in the low
      temperature combustion of dimethyl ether. The kinetics and yields of OH from the
      reaction of the methoxymethyl radical with O2 have been measured over the
      temperature and pressure ranges of 195-650 K and 5-500 Torr by detecting the
      hydroxyl radical using laser-induced fluorescence following the excimer laser
      photolysis (248 nm) of CH3OCH2Br. The reaction proceeds via the formation of an
      energized CH3OCH2O2 adduct, which either dissociates to OH + 2 H2CO or is
      collisionally stabilized by the buffer gas. At temperatures above 550 K, a
      secondary source of OH was observed consistent with thermal decomposition of
      stabilized CH3OCH2O2 radicals. In order to quantify OH production from the
      CH3OCH2 + O2 reaction, extensive relative and absolute OH yield measurements were
      performed over the same (T, P) conditions as the kinetic experiments. The
      reaction was studied at sufficiently low radical concentrations (~10(11) cm(-3))
      that secondary (radical + radical) reactions were unimportant and the rate
      coefficients could be extracted from simple bi- or triexponential analysis. Ab
      initio (CBS-GB3)/master equation calculations (using the program MESMER) of the
      CH3OCH2 + O2 system were also performed to better understand this combustion
      related reaction as well as be able to extrapolate experimental results to higher
      temperatures and pressures. To obtain agreement with experimental results (both
      kinetics and yield data), energies of the key transition states were
      substantially reduced (by 20-40 kJ mol(-1)) from their ab initio values and the
      effect of hindered rotations in the CH3OCH2 and CH3OCH2OO intermediates were
      taken into account. The optimized master equation model was used to generate a
      set of pressure and temperature dependent rate coefficients for the component
      nine phenomenological reactions that describe the CH3OCH2 + O2 system, including
      four well-skipping reactions. The rate coefficients were fitted to Chebyshev
      polynomials over the temperature and density ranges 200 to 1000 K and 1 * 10(17)
      to 1 * 10(23) molecules cm(-3) respectively for both N2 and He bath gases.
      Comparisons with an existing autoignition mechanism show that the well-skipping
      reactions are important at a pressure of 1 bar but are not significant at 10 bar.
      The main differences derive from the calculated rate coefficient for the
      CH3OCH2OO -> CH2OCH2OOH reaction, which leads to a faster rate of formation of
      O2CH2OCH2OOH. 

PMID- 25069060
TI  - The theoretical limit to plant productivity.
AB  - Human population and economic growth are accelerating the demand for plant
      biomass to provide food, fuel, and fiber. The annual increment of biomass to meet
      these needs is quantified as net primary production (NPP). Here we show that an
      underlying assumption in some current models may lead to underestimates of the
      potential production from managed landscapes, particularly of bioenergy crops
      that have low nitrogen requirements. Using a simple light-use efficiency model
      and the theoretical maximum efficiency with which plant canopies convert solar
      radiation to biomass, we provide an upper-envelope NPP unconstrained by resource
      limitations. This theoretical maximum NPP approached 200 tC ha(-1) yr(-1) at
      point locations, roughly 2 orders of magnitude higher than most current managed
      or natural ecosystems. Recalculating the upper envelope estimate of NPP limited
      by available water reduced it by half or more in 91% of the land area globally.
      While the high conversion efficiencies observed in some extant plants indicate
      great potential to increase crop yields without changes to the basic mechanism of
      photosynthesis, particularly for crops with low nitrogen requirements, realizing
      such high yields will require improvements in water use efficiency. 

PMID- 25069061
TI  - Highly cis-selective and lead-free hydrogenation of 2-hexyne by a supported Pd
      catalyst with an ionic-liquid layer.
AB  - A simple Pd/SiO2 catalyst which was modified with the ionic liquid [BMPL][DCA]
      gave an excellent yield of 88% towards cis-2-hexene in the stereoselective
      hydrogenation of 2-hexyne. The catalyst outperforms, even at full conversion, the
      commonly used lead-poisoned, toxic Lindlar catalyst and supported colloidal-based
      Pd as well. 

PMID- 25069062
TI  - Impact of nutritional recovery with linear growth on the concentrations of
      adipokines in undernourished children living in Brazilian slums.
AB  - Undernutrition in early life has been reported to be closely associated with the
      development of non-communicable diseases in adulthood. Adequate treatment is
      important for reversing these effects. In the present study, we investigated the
      effects of undernutrition and anthropometric recovery on the weights and heights
      of children in relation to the concentrations of leptin, adiponectin and
      plasminogen activator inhibitor-1 (PAI-1). A total of 119 children (aged 6-16
      years) from the slums of Sao Paulo were selected according to their nutritional
      status and divided into three groups as follows: control (healthy without
      intervention, n 38) with a height-for-age Z score (HAZ) and a BMI-for-age Z score
      (BAZ) > -1.6; undernourished (HAZ and/or BAZ < -1.6, n 54); recovered from
      undernutrition (after treatment in a rehabilitation centre; HAZ and BAZ > -1.6, n
      27). Blood samples were collected to determine insulin, glucose, leptin,
      adiponectin and PAI-1 concentrations. Leptin concentrations in the undernourished
      group were lower than those in the control and recovered groups (mean 0.92 (95%
      CI 0.67, 1.25), 2.03 (95% CI 1.46, 2.82) and 1.66 (95% CI 1.15, 2.44) ng/ml,
      P=0.003), which had similar leptin concentrations. There were no differences in
      adiponectin and PAI-1 concentrations among the groups. A positive correlation
      between waist circumference and leptin concentrations was observed in all the
      girls and boys of the control group (control: r 0.729, P<0.01; undernourished: r
      0.490, P<0.05; and recovered: r 0.829, P<0.01; r 0.673, P<0.05). Stronger
      correlations between leptin and insulin concentrations were observed in the
      recovered group. The results of the present study indicate that normal leptin
      concentrations are found when normal height and weight are achieved.

PMID- 25069063
TI  - Dissolved uranium, radium and radon evolution in the Continental Intercalaire
      aquifer, Algeria and Tunisia.
AB  - Natural, dissolved (238)U-series radionuclides (U, (226)Ra, (222)Rn) and activity
      ratios (A.R.s: (234)U/(238)U; (228)Ra/(226)Ra) in Continental Intercalaire (CI)
      groundwaters and limited samples from the overlying Complexe Terminal (CT)
      aquifers of Algeria and Tunisia are discussed alongside core measurements for
      U/Th (and K) in the contexts of radiological water quality, geochemical controls
      in the aquifer, and water residence times. A redox barrier is characterised
      downgradient in the Algerian CI for which a trend of increasing (234)U/(238)U
      A.R.s with decreasing U-contents due to recoil-dominated (234)U solution under
      reducing conditions allows residence time modelling ~500 ka for the highest
      enhanced A.R. = 3.17. Geochemical modelling therefore identifies waters towards
      the centre of the Grand Erg Oriental basin as palaeowaters in line with reported
      (14)C and (36)Cl ages. A similar (234)U/(238)U trend is evidenced in a few of the
      Tunisian CI waters. The paleoage status of these waters is affirmed by both noble
      gas recharge temperatures and simple modelling of dissolved, radiogenic (4)He
      contents both for sampled Algerian and Tunisian CI and CT waters. For the regions
      studied these waters therefore should be regarded as "fossil" waters and treated
      effectively as a non-renewable resource. 

PMID- 25069064
TI  - Identifying recycled ash in basaltic eruptions.
AB  - Deposits of mid-intensity basaltic explosive eruptions are characterized by the
      coexistence of different types of juvenile clasts, which show a large variability
      of external properties and texture, reflecting alternatively the effects of
      primary processes related to magma storage or ascent, or of syn-eruptive
      modifications occurred during or immediately after their ejection. If fragments
      fall back within the crater area before being re-ejected during the ensuing
      activity, they are subject to thermally- and chemically-induced alterations.
      These 'recycled' clasts can be considered as cognate lithic for the
      eruption/explosion they derive. Their exact identification has consequences for a
      correct interpretation of eruption dynamics, with important implications for
      hazard assessment. On ash erupted during selected basaltic eruptions (at
      Stromboli, Etna, Vesuvius, Gaua-Vanuatu), we have identified a set of
      characteristics that can be associated with the occurrence of intra-crater
      recycling processes, based also on the comparison with results of reheating
      experiments performed on primary juvenile material, at variable temperature and
      under different redox conditions. 

PMID- 25069065
TI  - Comparative metabolomics in primates reveals the effects of diet and gene
      regulatory variation on metabolic divergence.
AB  - Human diets differ from those of non-human primates. Among few obvious
      differences, humans consume more meat than most non-human primates and regularly
      cook their food. It is hypothesized that a dietary shift during human evolution
      has been accompanied by molecular adaptations in metabolic pathways. Consistent
      with this notion, comparative studies of gene expression levels in primates have
      found that the regulation of genes with metabolic functions tend to evolve
      rapidly in the human lineage. The metabolic consequences of these regulatory
      differences, however, remained unknown. To address this gap, we performed a
      comparative study using a combination of gene expression and metabolomic
      profiling in livers from humans, chimpanzees, and rhesus macaques. We show that
      dietary differences between species have a strong effect on metabolic
      concentrations. In addition, we found that differences in metabolic concentration
      across species are correlated with inter-species differences in the expression of
      the corresponding enzymes, which control the same metabolic reaction. We
      identified a number of metabolic compounds with lineage-specific profiles,
      including examples of human-species metabolic differences that may be directly
      related to dietary differences. 

PMID- 25069066
TI  - Evaluation of Melia azedarach extracts against Streptococcus mutans.
AB  - Although the incidence of caries worldwide has declined in recent years, it is
      necessary to search for new means to overcome this disease and its
      microbiological agents. Phytochemistry can become an effective alternative to
      antibiotics, offering a promising strategy in the prevention and therapy of
      dental caries. This study aimed to evaluate in vitro the bactericide activity of
      a bioactive phytocomponent from Melia azedarach against Streptococcus mutans. The
      crude extract (CEx) from leaves and stem barks of M. azedarach in chloroform,
      petroleum ether, acetate ethyl, butanol, and aqueous fractions was evaluated
      using seven different concentrations. Disk diffusion and minimum inhibitory
      concentration assays were used to evaluate the antibacterial activity. 0.12%
      chlorhexidine was used as a positive control. The CEx and the petroleum ether
      fraction from M. azedarach showed significant antibacterial activity against S.
      mutans, confirming its antibiotic potential. 

PMID- 25069067
TI  - The unfolded protein response as a target for cancer therapy.
AB  - Various physiological and pathological conditions generate an accumulation of
      misfolded proteins in the endoplasmic reticulum (ER). This results in ER stress
      followed by a cellular response to cope with this stress and restore homeostasis:
      the unfolded protein response (UPR). Overall, the UPR leads to general
      translational arrest and the induction of specific factors to ensure cell
      survival or to mediate cell death if the stress is too severe. In multiple
      cancers, components of the UPR are overexpressed, indicating increased dependence
      on the UPR. In addition, the UPR can confer resistance to anti-cancer treatment.
      Therefore, modification of the UPR should be explored for its anti-cancer
      properties. This review discusses factors associated with the UPR that represent
      potential therapeutic targets. 

PMID- 25069068
TI  - The lateral brow: position in relation to age, gender, and ethnicity.
AB  - PURPOSE: Despite multiple studies regarding modes of eyebrow measurement and
      movement over time, the lateral aspect of the brow has been relatively ignored in
      the literature. Therefore, we arranged a study of the most lateral aspect of the
      eyebrow; in doing so, we hoped to ascertain the most practical line or angle of
      measurement. METHODS: In this cross-sectional study, adults age 18 years and
      older with no history of congenital or acquired periorbital or orbital pathology
      or surgery, brow tattooing or heavy plucking, phthisis, or strabismus were
      measured using a combination of in-office metrics and computer analysis. Subjects
      were asked to identify their ethnicity and country of origin. Models of age,
      gender, and ethnicity were created. RESULTS: One thousand twenty-four subjects
      were included (1,944 eyes). Measurements of nasal ala to lateral brow (NALB),
      lateral brow plumb line (LBPL; the vertical line between the tail of the brow and
      a horizontal line extending from the lateral canthus), and angle from the midbrow
      to the lateral brow tail showed statistically significant decline over time. The
      angle and LBPL varied mostly by ethnicity. The angle narrowed approximately 3
      degrees  per 20 years, while the LBPL fell approximately 2.5 mm per 20 years. The
      NALB varied most by age and fell approximately 3 mm per 20 years. CONCLUSIONS:
      The lateral tail of the brow descends with age. Measurements of its location and
      rate of change vary between genders and within ethnic groups. Two easily measured
      values-NALB and LBPL-can be used for preoperative planning and postoperative
      documentation.

PMID- 25069069
TI  - Assessment of bony nasolacrimal parameters among Asians.
AB  - PURPOSE: A case series evaluating racial differences in the nasolacrimal region
      and quantifying the anterior lacrimal crest thickness and minimum nasolacrimal
      duct diameter in Asians. METHODS: Facial or orbital CT scans of 90 consecutive
      patients were retrospectively reviewed. Evidence of lacrimal fossa tumor or
      trauma excluded a patient. Using 3-dimensional image software, the thickness of
      the anterior lacrimal crest, narrowest diameter of the nasolacrimal duct,
      vertical diameter of the lacrimal sac fossa, frontonasal angle, and inter
      frontozygomatic suture distance were measured in axial, sagittal, and coronal
      planes. RESULTS: Inter- and intraobserver correlation of a sample data proved
      reliability via intraclass correlation coefficient (0.706-0.917). Southeast
      Asians had a wider inter-frontozygomatic suture distance than South Asian and
      Occidental races (p = 0.025). Vertical lacrimal fossa diameter, anterior lacrimal
      crest thickness, and narrowest nasolacrimal duct diameter did not differ
      significantly between right and left sides or among ethnic groups. Narrower
      nasolacrimal duct diameter was significantly associated with decreased inter
      frontozygomatic suture distance (p < 0.001), namely in patients with narrower
      faces. The anterior lacrimal crest thickness was significantly affected by the
      nasal configuration and thicker in patients with more acute frontonasal angle (p
      = 0.026). CONCLUSIONS: There is no significant difference in nasolacrimal duct
      diameter among ethnic groups, which may predispose one to nasolacrimal duct
      obstruction. But, this is significantly associated with inter-frontozygomatic
      suture distance, suggesting that a wider face is associated with wider
      nasolacrimal duct diameter. An acute frontonasal angle predicts a thicker
      anterior lacrimal crest for surgical preparation during dacryocystorhinostomy.

PMID- 25069070
TI  - Re: "Balloon dacryoplasty in internal ostium stenosis after endoscopic
      dacryocystorhinostomy".

PMID- 25069071
TI  - Reply re: "Balloon dacryoplasty in internal ostium stenosis after endoscopic
      dacryocystorhinostomy".

PMID- 25069072
TI  - Re: "Reactivation of thyroid eye disease following extraocular muscle surgery".

PMID- 25069073
TI  - Reply re: "Reactivation of thyroid eye disease following extraocular muscle
      surgery".

PMID- 25069074
TI  - Re: "Medial conjunctival resection for tearing associated with
      conjunctivochalasis".

PMID- 25069075
TI  - Reply re: "Medial conjunctival resection for tearing associated with
      conjunctivochalasis".

PMID- 25069076
TI  - Re: "Use of x-ray film for the repair of orbital blow out fractures".

PMID- 25069077
TI  - Reply re: "Use of sterilized x-ray film implant for the repair of orbital blow
      out fractures".

PMID- 25069078
TI  - Severe neutropenia presenting with Candida albicans eyelid abscess in a 1-year
      old child.

PMID- 25069079
TI  - Another case of neonatal progeroid syndrome and bilateral congenital upper eyelid
      entropion.

PMID- 25069081
TI  - Resilience to affective disorders: a comparative validation of two resilience
      scales.
AB  - BACKGROUND: Resilience to affective disorders in rehabilitating patients or in
      individuals with a severe disability is of special research interest. However,
      there is no gold standard for measuring resilience. We aimed to test the accuracy
      of the Dutch translation of the Brief Resilience Scale (BRSnl) and of the
      Resilience Scale (RSnl) in recognizing rehabilitating patients without anxiety
      and depression, and to determine the reliability and construct validity of both
      scales. METHODS: A within-subjects longitudinal study with six assessments, each
      one week apart. Forty residents of a nursing home rehabilitating unit were
      interviewed to assess resilience (BRSnl and RSnl), optimism and pessimism (LOT
      R), depression and anxiety (HADS), positive and negative affect (PANAS), and pain
      (VAS). RESULTS: Receiver operating characteristic analyses for recognizing the
      absence of depression and anxiety (HADS-score<=7) revealed better accuracy
      (P=0.038) for the BRSnl (AUC=0.84; p<0.0001) than for the RSnl (AUC=0.68;
      P=0.017). The scales correlated moderately at baseline (rs=0.35; p=0.026), and at
      four-week follow-up (rs=0.50; p=0.004). The RSnl was positively associated with
      positive outcomes (optimism and positive affect), and the BRSnl positively with
      positive outcomes, and negatively with negative outcomes (pessimism, anxiety and
      negative affect). The RSnl showed a better four-week test-retest reliability
      (ICC, 0.94; 95% CI, 0.87 to 0.97) than the BRSnl (0.66; 95% CI, 0.29 to.83).
      LIMITATIONS: Short study duration, a relatively small sample. CONCLUSION: The
      BRSnl showed better performance in detecting people without depression and
      anxiety than the RSnl, and performed better on construct validity.

PMID- 25069082
TI  - A systematic review and meta-analysis of lithium augmentation of tricyclic and
      second generation antidepressants in major depression.
AB  - BACKGROUND: Lithium augmentation of antidepressants for treatment of unipolar
      major depression was one of the first adjunctive strategies based on a
      neuropharmacologic rationale. Randomized controlled trials supported its efficacy
      but most trials added lithium to tricyclic antidepressants (TCAs). Despite its
      efficacy, use of lithium augmentation remains infrequent. The current systematic
      review and meta-analysis examines the efficacy of lithium augmentation as an
      adjunct to second generation antidepressants as well as to TCAs and considers
      reasons for its infrequent use. METHOD: A systematic search of Medline and the
      Cochrane Clinical Trials database was performed. Randomized, placebo-controlled
      trials of lithium augmentation were selected. A fixed-effects meta-analysis was
      performed. Odds ratios for response were calculated for each treatment-control
      contrast, for the trials grouped by type of initial antidepressant (TCA or second
      generation antidepressant), and as a meta-analytic summary for all treatments
      combined. RESULTS: Nine trials that included 237 patients were selected. The odds
      ratio for response to lithium vs. placebo in all contrasts combined was 2.89 (95%
      CI 1.65, 5.05, z=3.72, p=0.0002). Heterogeneity was very low, I(2)=0%. Adjunctive
      lithium was effective with TCAs (7 contrasts) and with second generation agents
      (3 contrasts). Discontinuation due to adverse events was infrequent and did not
      differ between lithium and placebo. LIMITATIONS: The meta-analysis is limited by
      the small size and number of trials and limited data for treatment resistant
      patients. CONCLUSIONS: Adjunctive lithium appears to be as effective for second
      generation antidepressants as it was for the tricyclics.

PMID- 25069083
TI  - Nitroreductase-activatable morpholino oligonucleotides for in vivo gene
      silencing.
AB  - Phosphorodiamidate morpholino oligonucleotides are widely used to interrogate
      gene function in whole organisms, and light-activatable derivatives can reveal
      spatial and temporal differences in gene activity. We describe here a new class
      of caged morpholino oligonucleotides that can be activated by the bacterial
      nitroreductase NfsB. We characterize the activation kinetics of these reagents in
      vitro and demonstrate their efficacy in zebrafish embryos that express NfsB
      either ubiquitously or in defined cell populations. In combination with
      transgenic organisms, such enzyme-actuated antisense tools will enable gene
      silencing in specific cell types, including tissues that are not amenable to
      optical targeting. 

PMID- 25069080
TI  - Differential abnormalities of functional connectivity of the amygdala and
      hippocampus in unipolar and bipolar affective disorders.
AB  - OBJECTIVE: The amygdala and hippocampus - two structures intimately associated
      with mood and cognition - have been reported to exhibit altered neural activity
      or volume in affective disorders. We hypothesized the amygdala and hippocampus
      would show altered and differential patterns of connectivity in patients with
      bipolar (BPs) and unipolar (UPs) disorder compared to healthy volunteers. METHOD:
      Thirty BPs, 34 UPs, and 66 healthy volunteers were imaged using F-18
      fluorodeoxyglucose and positron emission tomography while performing an auditory
      continuous performance task (CPT). Normalized mean activity of the amygdala and
      hippocampus was correlated with the rest of the brain. RESULTS: In BPs, the
      amygdalae displayed exaggerated positive metabolic correlations with prefrontal
      and ventral striatal areas, while the hippocampus showed a paucity of normal
      inter-relations compared to controls. In contrast, in UPs the amygdala was
      significantly negatively correlated with prefrontal and anterior cingulate
      cortex, while the hippocampus was significantly more positively correlated to
      these same prefrontal areas. CONCLUSIONS: During a simple cognitive task, the
      functional connectivity of the amygdala and hippocampus, regions usually
      associated with emotion and memory regulation, was substantially different in
      affective illness compared to healthy controls whether or not there were baseline
      abnormalities in these areas. These striking differences in functional
      connectivity of amygdala and hippocampus should be further explored in ill and
      well states and using more specific emotion and cognitive evocative tasks.

PMID- 25069084
TI  - Indimicins A-E, Bisindole Alkaloids from the Deep-Sea-Derived Streptomyces sp.
      SCSIO 03032.
AB  - Five new bisindole alkaloids, indimicins A-E (1-5), bearing a unique 1',3'
      dimethyl-2'-hydroindole moiety, were isolated from the marine-derived
      Streptomyces sp. SCSIO 03032, along with two new compounds, lynamicins F and G (6
      and 7). Their planar structures were elucidated by detailed interpretation of
      their MS and NMR spectroscopic data, and the absolute configurations were
      determined by X-ray crystallographic analysis (for 1), comparison of CD spectra
      (for 2-4), and quantum chemical calculations (for 5). Indimicin B (2) exhibited
      moderate cytotoxic activity toward the MCF-7 cell line. 

PMID- 25069085
TI  - Heterogeneous binary interactions of taste primaries: perceptual outcomes,
      physiology, and future directions.
AB  - Complex taste experiences arise from the combinations of five taste primaries.
      Here we review the literature on binary interactions of heterogeneous taste
      primaries, focusing on perceptual results of administering mixtures of aqueous
      solutions to human participants. Some interactions proved relatively consistent
      across tastants and experimental methods: sour acids enhanced saltiness, salts
      and sweeteners suppressed bitterness, sweeteners suppressed sourness, and sour
      acids enhanced bitterness. However, for the majority of interactions there were
      differential effects based on the tastants and their concentrations. Drawing
      conclusions about interactions with umami is currently not possible due to the
      low number of primary source studies investigating it and the confounding sodium
      ions in monosodium glutamate (MSG). Speculative physiological explanations are
      provided that fit the current data and suggestions for future research studies
      are proposed. 

PMID- 25069087
TI  - Dual quinone tagging for MALDI-TOF mass spectrometric quantitation of cysteine
      containing peptide.
AB  - A dual quinone tagging strategy is designed for quantitation of cysteine
      containing peptide (CCP) with MALDI-TOF mass spectrometry. The quinone compounds
      can rapidly and specifically bind to the thiol group of cysteine residues by a
      Michael addition reaction, which is used to identify both CCP and the number of
      cysteine residues in CCP through the direct observation of untagged and tagged
      products. After reduced with DL-dithiothreitol, the intramolecular disulfide bond
      can also be identified. Using benzoquinone (BQ) and methyl-p-benzoquinone (MBQ)
      as dual tags and a peptide with an amino acid sequence of SSDQFRPDDCT (C-pep1) as
      a model target, respectively, the quantitation strategy is performed through the
      intensity ratio of MBQ-tagged C-pep1 to BQ-tagged C-pep1 as the internal
      standard. The logarithm value of the intensity ratio is proportional to C-pep1
      concentration in a range from 5.0 to 5000 nM. The limit of detection is as low as
      2.0 nM. The proposed methodology provides a novel tool for rapid
      characterization, identification, and quantitation of biomolecules containing
      thiol reactive sites and has a promising application in the large-scale detection
      and analysis of cysteine-containing biomolecules. 

PMID- 25069086
TI  - Levels and profile of several classes of organic contaminants in matched indoor
      dust and serum samples from occupational settings of Pakistan.
AB  - Dust ingestion is an important route of human exposure to organic contaminants,
      especially for flame retardants (FRs) in occupational settings. Several classes
      of organic contaminants were analyzed in matched dust and serum samples from
      academics and workers in electronics and clothing stores of Faisalabad, Pakistan.
      The concentrations of contaminants varied in dust as follow: organophosphate FRs
      (?PFRs) > novel brominated FRs (?NBFRs) > polybrominated diphenyl ethers (?PBDEs)
      > organochlorine pesticides (?OCPs) > polychlorinated biphenyls (?PCBs), while,
      in serum, concentration varied: ?OCPs > bromophenols (?BPs) > ?PCBs > ?HO-PCBs ~
      ?PBDEs. Two NBFRs, namely 1,2-bis(2,4,6-tribromophenoxy)-ethane (BTBPE) and bis(2
      ethylhexyl) tetrabromophthalate (TBPH), were detected in <10% of the serum
      samples. p,p'-DDE was the major contaminant in serum contributing to ~75% of the
      total contaminant burden. Levels of Penta-BDE congeners in serum and dust were
      significantly correlated (r = 0.64, p < 0.01) for the academics, suggesting dust
      ingestion as an important determinant for their serum levels. 

PMID- 25069088
TI  - Differences in the secretion pattern of oxidoreductases from Bjerkandera adusta
      induced by a phenolic olive mill extract.
AB  - The secretome of the white-rot fungus Bjerkandera adusta produced in synthetic
      Kirk medium was compared to that supplemented with an aqueous phenol-rich extract
      of dry olive mill residues (ADOR). Distinct changes in the protein composition of
      oxidoreductases, namely diverse class-II peroxidases and aryl alcohol oxidases
      were found. In the ADOR-supplemented medium (ASC), 157 distinct proteins were
      identified by the secretome analysis, whereas only 59 of them were identified
      without ADOR supplementation (Kirk medium culture; KM). Proteome analysis
      indicated that the number of peroxidases produced in ASC was more than doubled
      (from 4 to 11) compared to KM. Two short manganese peroxidases (MnP1 and MnP6)
      and one versatile peroxidase (VP1) represented 29% of the relative abundance
      (NSAF) in ASC. Two of them (MnP1 and VP1) were also detected in KM at a relative
      abundance (NSAF) of only 3%. Further peroxidases present in ASC were one lignin
      peroxidase (LiP2), one generic peroxidase (GP) and three dye-decolorizing
      peroxidases (DyPs). The relative abundance of DyPs and aryl alcohol oxidases
      (AAO) were lower in ASC in comparison to KM. In addition to peptide sequence
      analysis, the secretion of Mn(2+)-oxidizing peroxidases as well as AAOs were
      followed by enzyme measurement. The Mn(2+)-oxidizing activity increased nearly 30
      fold (from 10 to 281Ul(-1)) after ADOR addition. Two enzymes responsible for that
      activity were successfully purified (BadVPI and BadVPII). To prove a potential
      involvement of these enzymes in the degradation of aromatic compounds, BadVPI was
      tested for its ability to degrade the recalcitrant dehydrogenated polymer (DHP,
      synthetic lignin). These results show that natural phenol-rich materials act as
      secretome-stimulating additives. Applying these substances enables us to
      investigate fungal degradation and detoxification processes and gives more
      insight into the complexity of fungal secretomes, e.g. of white-rot fungi. 

PMID- 25069090
TI  - Differences in forebrain androgen receptor expression in winners and losers of
      male anole aggressive interactions.
AB  - Size matched male green anoles (Anolis carolinensis) were paired in a neutral
      setting and allowed to engage in aggressive displays. Winners and losers were
      apparent in each pair within 90min, resulting in stable dominant/subordinate
      dyads. Androgen receptor (AR) expression was assessed at three time points after
      the initial pairing, 2h, 3 days, and 10 days in dominants, subordinates, and two
      groups of control males housed alone or with a female for an equal period of
      time. Expression was quantified in three forebrain areas that have been
      implicated in aggression and reproductive social behavior in this species, the
      preoptic area (POA), the anterior hypothalamus (AH), septal area (SEP), and
      ventromedial nucleus of the posterior division of the dorsal ventricular ridge
      (PDVRVM ). There were significant overall group differences in AR mRNA expression
      in the POA and AH that appeared to result from higher POA AR expression in
      dominant males compared to other groups, and generally lower AR expression in
      subordinate males. Pairwise comparison revealed that dominants' AR mRNA
      expression in the POA was significantly higher in the 2h and 3 day groups
      compared to that of subordinates, with a similar, but nonsignificant, difference
      in the 10 day group. Dominants had significantly higher AR mRNA expression in the
      AH compared to that of subordinates in the 2h group, but differences were not
      significant at later times. The results suggest that POA and AH sensitivity to
      androgens is increased in dominants compared to subordinates, and that the
      difference can be seen soon after the agonistic interaction establishing winners
      and losers. 

PMID- 25069091
TI  - Attraction of mesoscale objects on the surface of a thin elastic film supported
      on a liquid.
AB  - We study the interaction of two parallel rigid cylinders on the surface of a thin
      elastic film supported on a pool of liquid. The excess energy of the surface due
      to the curvature of the stretched film induces attraction of the cylinders that
      can be quantified by the variation of their gravitational potential energies as
      they descend into the liquid while still floating on the film. Although the
      experimental results follow the trend predicted from the balance of the
      gravitational and elastic energies of the system, they are somewhat
      underestimated. The origin of this discrepancy is the hysteresis of adhesion
      between the cylinder and the elastic film that does not allow the conversion of
      the total available energy into gravitational potential energy, as some part of
      it is recovered in stretching the film behind the cylinders while they approach
      each other. A modification of the model accounting for the effects of adhesion
      hysteresis improves the agreement between theoretical and experimental results.
      The contribution of the adhesion hysteresis can be reduced considerably by
      introducing a thin hydrogel layer atop the elastic film that enhances the range
      of attraction of the cylinders (as well as rigid spheres) in a dramatic way.
      Morphological instabilities in the gel project corrugated paths to the motion of
      small spheres, thus leading to a large numbers of particles to aggregate along
      their defects. These observations suggest that a thin hydrogel layer supported on
      a deformable elastic film affords an effective model system to study elasticity
      and defects mediated interaction of particles on its surface. 

PMID- 25069092
TI  - The mutual co-regulation of extracellular polymeric substances and iron ions in
      biocorrosion of cast iron pipes.
AB  - New insights into the biocorrosion process may be gained through understanding of
      the interaction between extracellular polymeric substances (EPS) and iron.
      Herein, the effect of iron ions on the formation of biofilms and production of
      EPS was investigated. Additionally, the impact of EPS on the corrosion of cast
      iron coupons was explored. The results showed that a moderate concentration of
      iron ions (0.06 mg/L) promoted both biofilm formation and EPS production. The
      presence of EPS accelerated corrosion during the initial stage, while inhibited
      corrosion at the later stage. The functional groups of EPS acted as electron
      shuttles to enable the binding of iron ions. Binding of iron ions with EPS led to
      anodic dissolution and promoted corrosion, while corrosion was later inhibited
      through oxygen reduction and availability of phosphorus from EPS. The presence of
      EPS also led to changes in crystalline phases of corrosion products.

PMID- 25069089
TI  - Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse
      models of Alexander disease.
AB  - Alexander disease (AxD) is the only known human pathology caused by mutations in
      an astrocyte-specific gene, glial fibrillary acidic protein (GFAP). These
      mutations result in abnormal GFAP accumulations that promote seizures, motor
      delays and, ultimately, death. The exact contribution of increased, abnormal
      levels of astrocytic mutant GFAP in the development and progression of the
      epileptic phenotype is not clear, and we addressed this question using two mouse
      models of AxD. Comparison of brain seizure activity spontaneously and after
      traumatic brain injury (TBI), an effective way to trigger seizures, revealed that
      abnormal GFAP accumulation contributes to anomalous brain activity (increased non
      convulsive hyperactivity) but is not a risk factor for the development of
      epilepsy after TBI. These data highlight the need to further explore the complex
      and heterogeneous response of astrocytes towards injury and the involvement of
      GFAP in the progression of AxD. 

PMID- 25069093
TI  - Enhanced nitrogen removal in constructed wetlands: effects of dissolved oxygen
      and step-feeding.
AB  - Four horizontal subsurface flow constructed wetlands (HSFCWs), named HSFCW1
      (three-stage, without step-feeding), HSFCW2 (three-stage, with step-feeding),
      HSFCW3 (five-stage, without step-feeding) and HSFCW4 (five-stage, with step
      feeding) were designed to investigate the effects of dissolved oxygen (DO) and
      step-feeding on nitrogen removal. High removal of 90.9% COD, 99.1% ammonium
      nitrogen and 88.1% total nitrogen (TN) were obtained simultaneously in HSFCW4
      compared with HSFCW1-3. The excellent TN removal of HSFCW4 was due to artificial
      aeration provided sufficient DO for nitrification and the favorable anoxic
      environment created for denitrification. Step-feeding was a crucial factor
      because it provided sufficient carbon source (high COD: nitrate ratio of 14.3)
      for the denitrification process. Microbial activities and microbial abundance in
      HSFCW4 was found to be influenced by DO distribution and step-feeding, and thus
      improve TN removal. These results suggest that artificial aeration combined with
      step-feeding could achieve high nitrogen removal in HSFCWs. 

PMID- 25069094
TI  - Polyethylenimine modified biochar adsorbent for hexavalent chromium removal from
      the aqueous solution.
AB  - A chemical modified biochar with abundant amino groups for heavy metal removal
      was prepared using polyethylenimine (PEI) as a modification reagent, and used as
      an adsorbent for the removal of Cr(VI) from aqueous solution. The biochars before
      and after modification were characterized by Fourier transformed infrared
      spectroscopy, X-ray photoelectron spectroscopy etc. The adsorption of Cr(VI) by
      the modified biochar was obeyed pseudo-second-order kinetic model and Langmuir
      adsorption isotherm model. Its maximum adsorption capacity was 435.7 mg/g, which
      was much higher than that of pristine biochar (23.09 mg/g). Results also
      indicated that the removal of Cr(VI) by the PEI modified biochar depended on
      solution pH, and a low pH value was favorable for the Cr(VI) removal. The results
      herein revealed that the PEI modified biochar had a good potential as a suitable
      material for sorption and detoxification of Cr(VI) from aqueous solution.

PMID- 25069095
TI  - Floatation of flocculent and granular sludge in a high-loaded anammox reactor.
AB  - The floatation of flocculent and granular sludge was investigated in this study.
      An anaerobic ammonium oxidation (anammox) upflow anaerobic sludge blanket (UASB)
      reactor was operated for 665 days. During this time, the maximum nitrogen removal
      rate was 52.6 kg Nm(-3) d(-1). Floccule floatation occurred between days 100 and
      140, which potentially resulted from the sudden increase in gas yield and the
      poor settling ability of the floccules. Increasing the shear rate from 0.084 to
      0.135 s(-1) was effective at eliminating floccule floatation. In addition,
      granule floatation occurred between days 572 and 665, which likely resulted from
      the formation of hollows within the granules. Floatation may be effectively
      prevented by maintaining a shear rate of more than 0.778 s(-1). Furthermore, the
      mechanisms of granule floatation and the floatation processes were proposed.
      Overall, controlling the shear force may effectively overcome sludge floatation.

PMID- 25069096
TI  - Determination of chrysotoxine in rat plasma by liquid chromatography-tandem mass
      spectrometry and its application to a rat pharmacokinetic study.
AB  - Chrysotoxine (CTX), a naturally occurring bibenzyl compound isolated from
      Dendrobium species, has been reported to have neuroprotective effects. To
      evaluate its pharmacokinetics in rats, a rapid, sensitive and specific high
      performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method
      has been developed and validated for the quantification of CTX in rat plasma.
      Samples were pretreated using a simple liquid-liquid extraction with ethyl
      acetate and the chromatographic separation was performed on a C18 column with
      acetonitrile-water (90:10, v/v) as the mobile phase. CTX and the internal
      standard (wogonin) were detected using a tandem mass spectrometer in positive
      multiple reaction monitoring mode. Method validation revealed excellent linearity
      over the range 0.5-1000 ng/mL together with satisfactory intra- and inter-day
      precision, accuracy and recovery. Stability testing showed that CTX spiked into
      rat plasma was stable for 8 h at room temperature, for up to two weeks at -20 
      degrees C, and during three freeze-thaw cycles. Extracted samples were also
      observed to be stable over 24 h in an auto-sampler. The method was successfully
      used to investigate the pharmacokinetic profile of CTX after oral (100 mg/kg) and
      intravenous (25 mg/kg) administration in rats. CTX showed rapid excretion and low
      bioavailability in rats.

PMID- 25069097
TI  - Rats with altered behaviour following nerve injury show evidence of centrally
      altered thyroid regulation.
AB  - The co-morbidity of mood disturbance, in a proportion of patients, is now
      described across a wide range of chronic disease states. Similarly, a 'Low
      Thyroid Syndrome' is also reported in a proportion of individuals with chronic
      diseases. Here, we report on central changes in an animal model of inflammatory
      stress in which altered social behaviour, representing social disability,
      persists in a sub-group of rats following injury. We showed in an earlier study
      that rats with social disability following injury have significantly decreased
      peripheral thyroid hormones, with no increase in Thyroid Stimulating Hormone
      (TSH). Only rats identified by behavioural change showed changes in hypothalamic
      gene expression. In whole hypothalamus extracted RNA, relative expression of mRNA
      for Thyrotrophin-releasing hormone (TRH) was significantly down-regulated in
      disabled rats (p=0.039) and deiodinase 3 up-regulated (p=0.006) compared to
      controls. Specifically in the paraventricular nucleus (PVN), numbers of
      immunoreactive cells for deiodinase 3-like and thyroid hormone receptor beta-like
      proteins were decreased in the sub-group with disability compared to the control
      group (p=0.031 and p=0.011 respectively). In rats with behavioural change post
      injury, down-regulation of TRH provides an explanation for the failure of the
      hypothalamo-pituitary-thyroid (HPT) axis to respond to the post-injury decrease
      in thyroxine. Decreased local expression of deiodinase 3 protein, resulting in a
      local increase in T3, offers an explanation for down regulation of TRH in the
      hypophysiotrophic TRH neurons. It is possible that, in a sub-group of animals
      identified behaviourally, a mechanism resulting in hypothalamic down-regulation
      of the HPT axis persists following inflammatory injury. 

PMID- 25069098
TI  - OTJR: Occupation, Participation and Health now indexed by the National Library of
      Medicine.

PMID- 25069099
TI  - The correlation between physical activity and grade point average for health
      science graduate students.
AB  - Researchers have reported positive associations between physical activity and
      academic achievement. However, a common belief is that improving academic
      performance comes at the cost of reducing time for and resources spent on
      extracurricular activities that encourage physical activity. The purpose of this
      study was to examine the relationship between self-reported physical activity and
      grade point average (GPA) for health science graduate students. Graduate students
      in health science programs completed the International Physical Activity
      Questionnaire and reported their academic progress. Most participants (76%)
      reported moderate to vigorous physical activity levels that met or exceeded the
      recommended levels for adults. However, there was no significant correlation
      between GPA and level of physical activity. Negative findings for this study may
      be associated with the limited range of GPA scores for graduate students. Future
      studies need to consider more sensitive measures of cognitive function, as well
      as the impact of physical activity on occupational balance and health for
      graduate students in the health fields.

PMID- 25069100
TI  - Twin boundary profiles with linear-quadratic coupling between order parameters.
AB  - A new type of twin boundary was found when two order parameters interact by
      linear-quadratic coupling QP(2). In this solution, we find that a domain wall
      consists of two layers in which in one layer both order parameters Q and P are
      active while in the second layer only Q is active. The adjacent domains are
      equally asymmetric (Q, P) and (Q, 0) so that one phase could be polar and/or
      magnetic and contain a ferroelastic strain while the second layer is ferroelastic
      only without polar or magnetic properties. The two layers represent a stepwise
      transition between the two domains.We analyze the full phase diagram depending on
      the coupling constant and anisotropy of the gradient term, and show that in a
      certain regime the order parameter Q becomes activated only in the interfacial
      region. A common solution contains kinks and breathers whereby the width of the
      interface can be very wide in agreement with the first order character of the
      transition. 

PMID- 25069101
TI  - Denoising and artefact reduction in dynamic flat detector CT perfusion imaging
      using high speed acquisition: first experimental and clinical results.
AB  - Flat detector CT perfusion (FD-CTP) is a novel technique using C-arm angiography
      systems for interventional dynamic tissue perfusion measurement with high
      potential benefits for catheter-guided treatment of stroke. However, FD-CTP is
      challenging since C-arms rotate slower than conventional CT systems. Furthermore,
      noise and artefacts affect the measurement of contrast agent flow in tissue.
      Recent robotic C-arms are able to use high speed protocols (HSP), which allow
      sampling of the contrast agent flow with improved temporal resolution. However,
      low angular sampling of projection images leads to streak artefacts, which are
      translated to the perfusion maps. We recently introduced the FDK-JBF denoising
      technique based on Feldkamp (FDK) reconstruction followed by joint bilateral
      filtering (JBF). As this edge-preserving noise reduction preserves streak
      artefacts, an empirical streak reduction (SR) technique is presented in this
      work. The SR method exploits spatial and temporal information in the form of
      total variation and time-curve analysis to detect and remove streaks. The novel
      approach is evaluated in a numerical brain phantom and a patient study. An
      improved noise and artefact reduction compared to existing post-processing
      methods and faster computation speed compared to an algebraic reconstruction
      method are achieved. 

PMID- 25069102
TI  - The impact on CT dose of the variability in tube current modulation technology: a
      theoretical investigation.
AB  - Body CT scans are routinely performed using tube-current-modulation (TCM)
      technology. There is notable variability across CT manufacturers in terms of how
      TCM technology is implemented. Some manufacturers aim to provide uniform image
      noise across body regions and patient sizes, whereas others aim to provide lower
      noise for smaller patients. The purpose of this study was to conduct a
      theoretical investigation to understand how manufacturer-dependent TCM scheme
      affects organ dose, and to develop a generic approach for assessing organ dose
      across TCM schemes. The adult reference female extended cardiac-torso (XCAT)
      phantom was used for this study. A ray-tracing method was developed to calculate
      the attenuation of the phantom for a given projection angle based on phantom
      anatomy, CT system geometry, x-ray energy spectrum, and bowtie filter filtration.
      The tube current (mA) for a given projection angle was then calculated as a log
      linear function of the attenuation along that projection. The slope of this
      function, termed modulation control strength, alpha, was varied from 0 to 1 to
      emulate the variability in TCM technology. Using a validated Monte Carlo program,
      organ dose was simulated for five alpha values (alpha = 0, 0.25, 0.5, 0.75, and
      1) in the absence and presence of a realistic system mA limit. Organ dose was
      further normalized by volume-weighted CT dose index (CTDIvol) to obtain
      conversion factors (h factors) that are relatively independent of system
      specifics and scan parameters. For both chest and abdomen-pelvis scans and for 24
      radiosensitive organs, organ dose conversion factors varied with alpha, following
      second-order polynomial equations. This result suggested the need for alpha
      specific organ dose conversion factors (i.e., conversion factors specific to the
      modulation scheme used). On the other hand, across the full range of alpha
      values, organ dose in a TCM scan could be derived from the conversion factors
      established for a fixed-mA scan (hFIXED). This was possible by multiplying hFIXED
      by a revised definition of CTDIvol that accounts for two factors: (a) the tube
      currents at the location of an organ and (b) the variation in organ volume along
      the longitudinal direction. This alpha-generic approach represents an
      approximation. The error associated with this approximation was evaluated using
      the alpha-specific organ dose (i.e., the organ dose obtained by using alpha
      specific mA profiles as inputs into the Monte Carlo simulation) as the reference
      standard. When the mA profiles were constrained by a realistic system limit, this
      alpha-generic approach had errors of less than ~20% for the full range of alpha
      values. This was the case for 24 radiosensitive organs in both chest and abdomen
      pelvis CT scans with the exception of thyroid in the chest scan and bladder in
      the abdomen-pelvis scan. For these two organs, the errors were less than ~40%.
      The results of this theoretical study suggested that knowing the mA modulation
      profile and the fixed-mA conversion factors, organ dose may be estimated for a
      TCM scan independent of the specific modulation scheme applied. 

PMID- 25069103
TI  - Beam-specific planning volumes for scattered-proton lung radiotherapy.
AB  - This work describes the clinical implementation of a beam-specific planning
      treatment volume (bsPTV) calculation for lung cancer proton therapy and its
      integration into the treatment planning process. Uncertainties incorporated in
      the calculation of the bsPTV included setup errors, machine delivery variability,
      breathing effects, inherent proton range uncertainties and combinations of the
      above. Margins were added for translational and rotational setup errors and
      breathing motion variability during the course of treatment as well as for their
      effect on proton range of each treatment field. The effect of breathing motion
      and deformation on the proton range was calculated from 4D computed tomography
      data. Range uncertainties were considered taking into account the individual
      voxel HU uncertainty along each proton beamlet. Beam-specific treatment volumes
      generated for 12 patients were used: a) as planning targets, b) for routine plan
      evaluation, c) to aid beam angle selection and d) to create beam-specific margins
      for organs at risk to insure sparing. The alternative planning technique based on
      the bsPTVs produced similar target coverage as the conventional proton plans
      while better sparing the surrounding tissues. Conventional proton plans were
      evaluated by comparing the dose distributions per beam with the corresponding
      bsPTV. The bsPTV volume as a function of beam angle revealed some unexpected
      sources of uncertainty and could help the planner choose more robust beams. Beam
      specific planning volume for the spinal cord was used for dose distribution
      shaping to ensure organ sparing laterally and distally to the beam. 

PMID- 25069104
TI  - Turning manuscript rejection "lemons" into "lemonade".

PMID- 25069105
TI  - Quantification of rat brain SPECT with (123)I-ioflupane: evaluation of different
      reconstruction methods and image degradation compensations using Monte Carlo
      simulation.
AB  - SPECT studies with (123)I-ioflupane facilitate the diagnosis of Parkinson's
      disease (PD). The effect on quantification of image degradations has been
      extensively evaluated in human studies but their impact on studies of
      experimental PD models is still unclear. The aim of this work was to assess the
      effect of compensating for the degrading phenomena on the quantification of small
      animal SPECT studies using (123)I-ioflupane. This assessment enabled us to
      evaluate the feasibility of quantitatively detecting small pathological changes
      using different reconstruction methods and levels of compensation for the image
      degrading phenomena. Monte Carlo simulated studies of a rat phantom were
      reconstructed and quantified. Compensations for point spread function (PSF),
      scattering, attenuation and partial volume effect were progressively included in
      the quantification protocol. A linear relationship was found between calculated
      and simulated specific uptake ratio (SUR) in all cases. In order to significantly
      distinguish disease stages, noise-reduction during the reconstruction process was
      the most relevant factor, followed by PSF compensation. The smallest detectable
      SUR interval was determined by biological variability rather than by image
      degradations or coregistration errors. The quantification methods that gave the
      best results allowed us to distinguish PD stages with SUR values that are as
      close as 0.5 using groups of six rats to represent each stage. 

PMID- 25069107
TI  - An ingestible sensor for measuring medication adherence.
AB  - In this paper, we describe the design and performance of the first integrated
      circuit microsensor developed for daily ingestion by patients. The ingestible
      sensor is a device that allows patients, families, and physicians to measure
      medication ingestion and adherence patterns in real time, relate pharmaceutical
      compliance to important physiologic metrics, and take appropriate action in
      response to a patient's adherence pattern and specific health metrics. The design
      and theory of operation of the device are presented, along with key in-vitro and
      in-vivo performance results. The chemical, toxicological, mechanical, and
      electrical safety tests performed to establish the device's safety profile are
      described in detail. Finally, aggregate results from multiple clinical trials
      involving 412 patients and 5656 days of system usage are presented to demonstrate
      the device's reliability and performance as part of an overall digital health
      feedback system.

PMID- 25069108
TI  - Compressed sensing MRI via two-stage reconstruction.
AB  - Compressed sensing (CS) has been applied to magnetic resonance imaging for the
      acceleration of data collection. However, existing CS techniques usually produce
      images with residual artifacts, particularly at high reduction factors. In this
      paper, we propose a novel, two-stage reconstruction scheme, which takes advantage
      of the properties of k-space data and under-sampling patterns that are useful in
      CS. In this algorithm, the under-sampled k-space data is segmented into low
      frequency and high-frequency domains. Then, in stage one, using dense
      measurements, the low-frequency region of k-space data is faithfully
      reconstructed. The fully reconstituted low-frequency k-space data from the first
      stage is then combined with the high-frequency k-space data to complete the
      second stage reconstruction of the whole of k-space. With this two-stage
      approach, each reconstruction inherently incorporates a lower data under-sampling
      rate and more homogeneous signal magnitudes than conventional approaches. Because
      the restricted isometric property is easier to satisfy, the reconstruction
      consequently produces lower residual errors at each step. Compared with a
      conventional CS reconstruction, for the cases of cardiac cine, brain and
      angiogram imaging, the proposed method achieves a more accurate reconstruction
      with an improvement of 2-4 dB in peak signal-to-noise ratio respectively, using
      reduction factors of up to 6. 

PMID- 25069106
TI  - Quantitative understanding of pH- and salt-mediated conformational folding of
      histidine-containing, beta-hairpin-like peptides, through single-molecule probing
      with protein nanopores.
AB  - Inter-amino acid residues electrostatic interactions contribute to the
      conformational stability of peptides and proteins, influence their folding
      pathways, and are critically important to a multitude of problems in biology
      including the onset of misfolding diseases. By varying the pH and ionic strength,
      the inter-amino acid residues electrostatic interactions of histidine-containing,
      beta-hairpin-like peptides alter their folding behavior, and we studied this
      through quantifying, at the unimolecular level, the frequency, dwell-times of
      translocation events, and amplitude of blockades associated with interactions
      between such peptides and the alpha-hemolysin (alpha-HL) protein. Acidic buffers
      were shown to dramatically decrease the rate of peptide capture by the alpha-HL
      protein, through the interplay of enthalpic and entropic contributions brought
      about on the free energy barrier, which controls the peptides-alpha-HL
      association rate. We found that in acidic buffers, the amplitude of the blockage
      induced by an alpha-HL, beta-barrel-residing peptide is smaller than the value
      seen at neutral pH, and this supports our interpretation of the pH-induced change
      in the conformation of the peptide, which behaves as a less-stable hairpin at
      acidic pH values that obstructs, to a lesser extent, the protein pore. This is
      also confirmed by the fact that the dissociation rate of such model peptide from
      the alpha-HL's beta-barrel is higher at acidic, as compared to neutral, pH
      values. Experiments performed in low-salt buffers revealed the dramatic decrease
      of the peptide capture rate by the alpha-HL protein, most likely caused by the
      increase in the radius of counterions cloud around the peptide that hinders
      peptide partition into the alpha-barrel, and histidines protonation at low pH
      bolsters this effect. Reduced electrostatic screening in low-salt buffers, at
      neutral pH, leads to a decrease in peptides effective cross-sectional areas and
      an increase of their mobility inside the alpha-HL pore, due most likely to the
      chain stretching augmentation, via increased inter-residues electrostatic
      interactions. 

PMID- 25069109
TI  - A fast parallel solver for the forward problem in electrical impedance
      tomography.
AB  - Electrical impedance tomography (EIT) is a noninvasive imaging modality, where
      imperceptible currents are applied to the skin and the resulting surface voltages
      are measured. It has the potential to distinguish between ischaemic and
      haemorrhagic stroke with a portable and inexpensive device. The image
      reconstruction relies on an accurate forward model of the experimental setup.
      Because of the relatively small signal in stroke EIT, the finite-element modeling
      requires meshes of more than 10 million elements. To study the requirements in
      the forward modeling in EIT and also to reduce the time for experimental image
      acquisition, it is necessary to reduce the run time of the forward computation.
      We show the implementation of a parallel forward solver for EIT using the Dune
      Fem C++ library and demonstrate its performance on many CPU's of a computer
      cluster. For a typical EIT application a direct solver was significantly slower
      and not an alternative to iterative solvers with multigrid preconditioning. With
      this new solver, we can compute the forward solutions and the Jacobian matrix of
      a typical EIT application with 30 electrodes on a 15-million element mesh in less
      than 15 min. This makes it a valuable tool for simulation studies and EIT
      applications with high precision requirements. It is freely available for
      download.

PMID- 25069110
TI  - Multi-scale tubular structure detection in ultrasound imaging.
AB  - We propose a novel, physics-based method for detecting multi-scale tubular
      features in ultrasound images. The detector is based on a Hessian-matrix
      eigenvalue method, but unlike previous work, our detector is guided by an optimal
      model of vessel-like structures with respect to the ultrasound-image formation
      process. Our method provides a voxel-wise probability map, along with estimates
      of the radii and orientations of the detected tubes. These results can then be
      used for further processing, including segmentation and enhanced volume
      visualization. Most Hessian-based algorithms, including the well-known Frangi
      filter, were developed for CTA or MRA; they implicitly assume symmetry about the
      vessel centerline. This is not consistent with ultrasound data. We overcome this
      limitation by introducing a novel filter that allows multi-scale estimation both
      with respect to the vessel's centerline and with respect to the vessel's border.
      We use manually-segmented ultrasound imagery from 35 patients to show that our
      method is superior to standard Hessian-based methods. We evaluate the performance
      of the proposed methods based on the sensitivity and specificity like measures,
      and finally demonstrate further applicability of our method to vascular
      ultrasound images of the carotid artery, as well as ultrasound data for abdominal
      aortic aneurysms.

PMID- 25069111
TI  - Relating structural and functional connectivity in MRI: a simple model for a
      complex brain.
AB  - Advances in magnetic resonance imaging (MRI) allow to gain critical insight into
      the structure of neural networks and their functional dynamics. To relate
      structural connectivity [as quantified by diffusion-weighted imaging (DWI)
      tractography] and functional connectivity [as obtained from functional MRI
      (fMRI)], increasing emphasis has been put on computational models of brain
      activity. In the present study, we use structural equation modeling (SEM) with
      structural connectivity to predict functional connectivity. The resulting model
      takes the simple form of a spatial simultaneous autoregressive model (sSAR),
      whose parameters can be estimated in a Bayesian framework. On synthetic data,
      results showed very good accuracy and reliability of the inference process. On
      real data, we found that the sSAR performed significantly better than two other
      reference models as well as than structural connectivity alone, but that the
      Bayesian procedure did not bring significant improvement in fit compared to two
      simpler approaches. Nonetheless, we also found that the values of the region
      specific parameters inferred using Bayesian inference differed significantly
      across resting-state networks. These results demonstrate 1) that a simple
      abstract model is able to perform better that more complex models based on more
      realistic assumptions, 2) that the parameters of the sSAR can be estimated and
      can potentially be used as biomarkers, but also 3) that the sSAR, while being the
      best-performing model, is at best still a very crude model of the relationship
      between structure and function in MRI.

PMID- 25069112
TI  - Effective CU size decision for HEVC intracoding.
AB  - In high efficiency video coding (HEVC), the tree structured coding unit (CU) is
      adopted to allow recursive splitting into four equally sized blocks. At each
      depth level (or CU size), it enables up to 35 intraprediction modes, including a
      planar mode, a dc mode, and 33 directional modes. The intraprediction via
      exhaustive mode search exploited in the test model of HEVC (HM) effectively
      improves coding efficiency, but results in a very high computational complexity.
      In this paper, a fast CU size decision algorithm for HEVC intracoding is proposed
      to speed up the process by reducing the number of candidate CU sizes required to
      be checked for each treeblock. The novelty of the proposed algorithm lies in the
      following two aspects: 1) an early determination of CU size decision with
      adaptive thresholds is developed based on the texture homogeneity and 2) a novel
      bypass strategy for intraprediction on large CU size is proposed based on the
      combination of texture property and coding information from neighboring coded
      CUs. Experimental results show that the proposed effective CU size decision
      algorithm achieves a computational complexity reduction up to 67%, while
      incurring only 0.06-dB loss on peak signal-to-noise ratio or 1.08% increase on
      bit rate compared with that of the original coding in HM. 

PMID- 25069113
TI  - Self-similarity and Spectral Correlation Adaptive Algorithm for Color
      Demosaicking.
AB  - Most common cameras use a CCD sensor device measuring a single color per pixel.
      The other two color values of each pixel must be interpolated from the
      neighboring pixels in the so-called demosaicking process. State-of-the-art
      demosaicking algorithms take advantage of inter-channel correlation locally
      selecting the best interpolation direction. These methods give impressive results
      except when local geometry cannot be inferred from neighboring pixels or channel
      correlation is low. In these cases, they create interpolation artifacts. We
      introduce a new algorithm involving non-local image self-similarity in order to
      reduce interpolation artifacts when local geometry is ambiguous. The proposed
      algorithm introduces a clear and intuitive manner of balancing how much channel
      correlation must be taken advantage of. Comparison shows that the proposed
      algorithm gives state-of-the-art methods in several image bases.

PMID- 25069114
TI  - Linearly estimating all parameters of affine motion using Radon transform.
AB  - Fast and accurate motion estimation takes an important place in many fields of
      computer vision and image processing. Using Radon transform to compute
      projections of the images along specified directions is an effective way to show
      the relationship between the 2D image object and its projections and estimate
      motions between the images. All existing projection-based motion estimation
      methods without the use of iteration have a severe defect that only five of the
      six affine parameters can be estimated. There are some other methods that can
      estimate the six parameters, but most of them are usually based on a certain
      iterative framework, which is computationally intensive and sensitively dependent
      on the initial values. In this paper, a novel method based on Radon transform is
      proposed to estimate all the six affine parameters directly. The relationship in
      the projection domain between a pair of images connected by an affine motion is
      studied and a linear model is established, by which all the six affine parameters
      can be directively found. The employment of a hierarchical framework can produce
      more accurate results. The experimental results reveal that the proposed method
      has a much better performance than the state-of-the-art methods in this field. 

PMID- 25069115
TI  - A Novel Text Detection System Based on Character and Link Energies.
AB  - We propose a novel method by using three new character features to detect text
      objects comprising two or more isolated characters in images and videos. A new
      text model is constructed to describe text objects. Each character is a part in
      the model and every two neighboring characters are connected by a link. Two
      characters and the link connecting them are defined as a text unit. For every
      candidate part, we compute character energy based on our observation that each
      character stroke forms two edges with high similarities in length, curvature, and
      orientation. For every candidate link, we compute link energy based on the
      similarities in color, size, stroke width, and spacing between characters that
      are aligned along a particular direction. For every candidate text unit, we
      combine character and link energies to compute text unit energy which measures
      the likelihood that the candidate is a text object. We evaluated the performance
      of the proposed method on ICDAR 2003/2005 dataset, Microsoft Street view dataset,
      and VACE video dataset. The experimental results demonstrate that our method can
      capture the inherent properties of characters and discriminate text from other
      objects effectively.

PMID- 25069116
TI  - Generalized Nash Bargaining Solution to Rate Control Optimization for Spatial
      Scalable Video Coding.
AB  - Rate control (RC) optimization is indispensable for scalable video coding (SVC)
      with respect to bitstream storage and video streaming usage. From the perspective
      of centralized resource allocation optimization, the inner-layer bit allocation
      problem is similar to the bargaining problem. Therefore, bargaining game theory
      can be employed to improve the RC performance for spatial SVC. In this paper, we
      propose a bargaining game based one-pass RC scheme for spatial H.264/SVC. In each
      spatial layer (SL), the encoding constraints, such as bit rates, buffer size are
      jointly modeled as resources in the inner-layer bit allocation bargaining game.
      The modified rate-distortion (R-D) model incorporated with the inter-layer coding
      information is investigated. Then the generalized Nash bargaining solution (NBS)
      is employed to achieve an optimal bit allocation solution. The bandwidth is
      allocated to the frames from the generalized NBS adaptively based on their own
      bargaining powers. Experimental results demonstrate that the proposed rate
      control algorithm achieves appealing image quality improvement and buffer
      smoothness. The average mismatch of our proposed algorithm is within the range of
      0:19%2:63%.

PMID- 25069117
TI  - Improving filtered backprojection reconstruction by data-dependent filtering.
AB  - Filtered backprojection, one of the most widely used reconstruction methods in
      tomography, requires a large number of low-noise projections to yield accurate
      reconstructions. In many applications of tomography, complete projection data of
      high quality cannot be obtained, because of practical considerations. Algebraic
      methods tend to handle such problems better, but are computationally more
      expensive. In this paper, we introduce a new method that improves the filtered
      backprojection method by using a custom data-dependent filter that minimizes the
      projection error of the resulting reconstruction. We show that the computational
      cost of the new method is significantly lower than that of algebraic methods.
      Experiments on both simulation and experimental data show that the method is able
      to produce more accurate reconstructions than filtered backprojection based on
      popular static filters when presented with data with a limited number of
      projections or statistical noise present. Furthermore, the results show that the
      method produces reconstructions with similar accuracy to algebraic methods, but
      is faster at producing them. Finally, we show that the method can be extended to
      exploit certain forms of prior knowledge, improving reconstruction accuracy in
      specific cases. 

PMID- 25069118
TI  - A novel adaptive, real-time algorithm to detect gait events from wearable
      sensors.
AB  - A real-time, adaptive algorithm based on two inertial and magnetic sensors placed
      on the shanks was developed for gait-event detection. For each leg, the algorithm
      detected the Initial Contact (IC), as the minimum of the flexion/extension angle,
      and the End Contact (EC) and the Mid-Swing (MS), as minimum and maximum of the
      angular velocity, respectively. The algorithm consisted of calibration, real-time
      detection, and step-by-step update. Data collected from 22 healthy subjects (21
      to 85 years) walking at three self-selected speeds were used to validate the
      algorithm against the GaitRite system. Comparable levels of accuracy and
      significantly lower detection delays were achieved with respect to other
      published methods. The algorithm robustness was tested on ten healthy subjects
      performing sudden speed changes and on ten stroke subjects (43 to 89 years). For
      healthy subjects, F1-scores of 1 and mean detection delays lower than 14 ms were
      obtained. For stroke subjects, F1-scores of 0.998 and 0.944 were obtained for IC
      and EC, respectively, with mean detection delays always below 31 ms. The
      algorithm accurately detected gait events in real time from a heterogeneous
      dataset of gait patterns and paves the way for the design of closed-loop
      controllers for customized gait trainings and/or assistive devices. 

PMID- 25069119
TI  - A single-chip 32-channel analog beamformer with 4-ns delay resolution and 768-ns
      maximum delay range for ultrasound medical imaging with a linear array
      transducer.
AB  - A single-chip 32-channel analog beamformer is proposed. It achieves a delay
      resolution of 4 ns and a maximum delay range of 768 ns. It has a focal-point
      based architecture, which consists of 7 sub-analog beamformers (sub-ABF). Each
      sub-ABF performs a RX focusing operation for a single focal point. Seven sub-ABFs
      perform a time-interleaving operation to achieve the maximum delay range of 768
      ns. Phase interpolators are used in sub-ABFs to generate sampling clocks with the
      delay resolution of 4 ns from a low frequency system clock of 5 MHz. Each sub-ABF
      samples 32 echo signals at different times into sampling capacitors, which work
      as analog memory cells. The sampled 32 echo signals of each sub-ABF are
      originated from one target focal point at one instance. They are summed at one
      instance in a sub-ABF to perform the RX focusing for the target focal point. The
      proposed ABF chip has been fabricated in a 0.13- MU m CMOS process with an active
      area of 16 mm (2). The total power consumption is 287 mW. In measurement, the
      digital echo signals from a commercial ultrasound medical imaging machine were
      applied to the fabricated chip through commercial DAC chips. Due to the speed
      limitation of the DAC chips, the delay resolution was relaxed to 10 ns for the
      real-time measurement. A linear array transducer with no steering operation is
      used in this work. 

PMID- 25069120
TI  - A 6 MUW per channel analog biomimetic cochlear implant processor filterbank
      architecture with across channels AGC.
AB  - A new analog cochlear implant processor filterbank architecture of increased
      biofidelity, enhanced across-channel contrast and very low power consumption has
      been designed and prototyped. Each channel implements a biomimetic, asymmetric
      bandpass-like One-Zero-Gammatone-Filter (OZGF) transfer function, using class-AB
      log-domain techniques. Each channel's quality factor and suppression are
      controlled by means of a new low power Automatic Gain Control (AGC) scheme which
      is coupled across the neighboring channels and emulates lateral inhibition (LI)
      phenomena in the auditory system. Detailed measurements from a five-channel
      silicon IC prototype fabricated in a 0.35 MUm AMS technology confirm the
      operation of the coupled AGC scheme and its ability to enhance contrast among
      channel outputs. The prototype is characterized by an input dynamic range of 92
      dB while consuming only 28 MUW of power in total ( ~ 6 MUW per channel) under a
      1.8 V power supply. The architecture is well-suited for fully-implantable
      cochlear implants.

PMID- 25069121
TI  - Adaptive NN controller design for a class of nonlinear MIMO discrete-time
      systems.
AB  - An adaptive neural network tracking control is studied for a class of multiple
      input multiple-output (MIMO) nonlinear systems. The studied systems are in
      discrete-time form and the discretized dead-zone inputs are considered. In
      addition, the studied MIMO systems are composed of N subsystems, and each
      subsystem contains unknown functions and external disturbance. Due to the
      complicated framework of the discrete-time systems, the existence of the dead
      zone and the noncausal problem in discrete-time, it brings about difficulties for
      controlling such a class of systems. To overcome the noncausal problem, by
      defining the coordinate transformations, the studied systems are transformed into
      a special form, which is suitable for the backstepping design. The radial basis
      functions NNs are utilized to approximate the unknown functions of the systems.
      The adaptation laws and the controllers are designed based on the transformed
      systems. By using the Lyapunov method, it is proved that the closed-loop system
      is stable in the sense that the semiglobally uniformly ultimately bounded of all
      the signals and the tracking errors converge to a bounded compact set. The
      simulation examples and the comparisons with previous approaches are provided to
      illustrate the effectiveness of the proposed control algorithm. 

PMID- 25069122
TI  - Further result on guaranteed Hinfinity performance state estimation of delayed
      static neural networks.
AB  - This brief considers the guaranteed Hinfinity performance state estimation
      problem of delayed static neural networks. An Arcak-type state estimator, which
      is more general than the widely adopted Luenberger-type one, is chosen to tackle
      this issue. A delay-dependent criterion is derived under which the estimation
      error system is globally asymptotically stable with a prescribed Hinfinity
      performance. It is shown that the design of suitable gain matrices and the
      optimal performance index are accomplished by solving a convex optimization
      problem subject to two linear matrix inequalities. Compared with some previous
      results, much better performance is achieved by our approach, which is greatly
      benefited from introducing an additional gain matrix in the domain of activation
      function. An example is finally given to demonstrate the advantage of the
      developed result. 

PMID- 25069123
TI  - Output-feedback adaptive neural control for stochastic nonlinear time-varying
      delay systems with unknown control directions.
AB  - This paper presents an adaptive output-feedback neural network (NN) control
      scheme for a class of stochastic nonlinear time-varying delay systems with
      unknown control directions. To make the controller design feasible, the unknown
      control coefficients are grouped together and the original system is transformed
      into a new system using a linear state transformation technique. Then, the
      Nussbaum function technique is incorporated into the backstepping recursive
      design technique to solve the problem of unknown control directions. Furthermore,
      under the assumption that the time-varying delays exist in the system output,
      only one NN is employed to compensate for all unknown nonlinear terms depending
      on the delayed output. Moreover, by estimating the maximum of NN parameters
      instead of the parameters themselves, the NN parameters to be estimated are
      greatly decreased and the online learning time is also dramatically decreased. It
      is shown that all the signals of the closed-loop system are bounded in
      probability. The effectiveness of the proposed scheme is demonstrated by the
      simulation results. 

PMID- 25069124
TI  - Memristor-based cellular nonlinear/neural network: design, analysis, and
      applications.
AB  - Cellular nonlinear/neural network (CNN) has been recognized as a powerful
      massively parallel architecture capable of solving complex engineering problems
      by performing trillions of analog operations per second. The memristor was
      theoretically predicted in the late seventies, but it garnered nascent research
      interest due to the recent much-acclaimed discovery of nanocrossbar memories by
      engineers at the Hewlett-Packard Laboratory. The memristor is expected to be co
      integrated with nanoscale CMOS technology to revolutionize conventional von
      Neumann as well as neuromorphic computing. In this paper, a compact CNN model
      based on memristors is presented along with its performance analysis and
      applications. In the new CNN design, the memristor bridge circuit acts as the
      synaptic circuit element and substitutes the complex multiplication circuit used
      in traditional CNN architectures. In addition, the negative differential
      resistance and nonlinear current-voltage characteristics of the memristor have
      been leveraged to replace the linear resistor in conventional CNNs. The proposed
      CNN design has several merits, for example, high density, nonvolatility, and
      programmability of synaptic weights. The proposed memristor-based CNN design
      operations for implementing several image processing functions are illustrated
      through simulation and contrasted with conventional CNNs. Monte-Carlo simulation
      has been used to demonstrate the behavior of the proposed CNN due to the
      variations in memristor synaptic weights. 

PMID- 25069125
TI  - Kernel reconstruction ICA for sparse representation.
AB  - Independent component analysis with soft reconstruction cost (RICA) has been
      recently proposed to linearly learn sparse representation with an overcomplete
      basis, and this technique exhibits promising performance even on unwhitened data.
      However, linear RICA may not be effective for the majority of real-world data
      because nonlinearly separable data structure pervasively exists in original data
      space. Meanwhile, RICA is essentially an unsupervised method and does not employ
      class information. Motivated by the success of the kernel trick that maps a
      nonlinearly separable data structure into a linearly separable case in a high
      dimensional feature space, we propose a kernel RICA (kRICA) model to nonlinearly
      capture sparse representation in feature space. Furthermore, we extend the
      unsupervised kRICA to a supervised one by introducing a class-driven
      discrimination constraint, such that the data samples from the same class are
      well represented on the basis of the corresponding subset of basis vectors. This
      discrimination constraint minimizes inhomogeneous representation energy and
      maximizes homogeneous representation energy simultaneously, which is essentially
      equivalent to maximizing between-class scatter and minimizing within-class
      scatter at the same time in an implicit manner. Experimental results demonstrate
      that the proposed algorithm is more effective than other state-of-the-art methods
      on several datasets. 

PMID- 25069126
TI  - Is extreme learning machine feasible? A theoretical assessment (part I).
AB  - An extreme learning machine (ELM) is a feedforward neural network (FNN) like
      learning system whose connections with output neurons are adjustable, while the
      connections with and within hidden neurons are randomly fixed. Numerous
      applications have demonstrated the feasibility and high efficiency of ELM-like
      systems. It has, however, been open if this is true for any general applications.
      In this two-part paper, we conduct a comprehensive feasibility analysis of ELM.
      In Part I, we provide an answer to the question by theoretically justifying the
      following: 1) for some suitable activation functions, such as polynomials,
      Nadaraya-Watson and sigmoid functions, the ELM-like systems can attain the
      theoretical generalization bound of the FNNs with all connections adjusted, i.e.,
      they do not degrade the generalization capability of the FNNs even when the
      connections with and within hidden neurons are randomly fixed; 2) the number of
      hidden neurons needed for an ELM-like system to achieve the theoretical bound can
      be estimated; and 3) whenever the activation function is taken as polynomial, the
      deduced hidden layer output matrix is of full column-rank, therefore the
      generalized inverse technique can be efficiently applied to yield the solution of
      an ELM-like system, and, furthermore, for the nonpolynomial case, the Tikhonov
      regularization can be applied to guarantee the weak regularity while not
      sacrificing the generalization capability. In Part II, however, we reveal a
      different aspect of the feasibility of ELM: there also exists some activation
      functions, which makes the corresponding ELM degrade the generalization
      capability. The obtained results underlie the feasibility and efficiency of ELM
      like systems, and yield various generalizations and improvements of the systems
      as well. 

PMID- 25069127
TI  - Learning from adaptive neural dynamic surface control of strict-feedback systems.
AB  - Learning plays an essential role in autonomous control systems. However, how to
      achieve learning in the nonstationary environment for nonlinear systems is a
      challenging problem. In this paper, we present learning method for a class of n
      th-order strict-feedback systems by adaptive dynamic surface control (DSC)
      technology, which achieves the human-like ability of learning by doing and doing
      with learned knowledge. To achieve the learning, this paper first proposes stable
      adaptive DSC with auxiliary first-order filters, which ensures the boundedness of
      all the signals in the closed-loop system and the convergence of tracking errors
      in a finite time. With the help of DSC, the derivative of the filter output
      variable is used as the neural network (NN) input instead of traditional
      intermediate variables. As a result, the proposed adaptive DSC method reduces
      greatly the dimension of NN inputs, especially for high-order systems. After the
      stable DSC design, we decompose the stable closed-loop system into a series of
      linear time-varying perturbed subsystems. Using a recursive design, the recurrent
      property of NN input variables is easily verified since the complexity is
      overcome using DSC. Subsequently, the partial persistent excitation condition of
      the radial basis function NN is satisfied. By combining a state transformation,
      accurate approximations of the closed-loop system dynamics are recursively
      achieved in a local region along recurrent orbits. Then, the learning control
      method using the learned knowledge is proposed to achieve the closed-loop
      stability and the improved control performance. Simulation studies are performed
      to demonstrate the proposed scheme can not only reuse the learned knowledge to
      achieve the better control performance with the faster tracking convergence rate
      and the smaller tracking error but also greatly alleviate the computational
      burden because of reducing the number and complexity of NN input variables. 

PMID- 25069128
TI  - Is extreme learning machine feasible? A theoretical assessment (part II).
AB  - An extreme learning machine (ELM) can be regarded as a two-stage feed-forward
      neural network (FNN) learning system that randomly assigns the connections with
      and within hidden neurons in the first stage and tunes the connections with
      output neurons in the second stage. Therefore, ELM training is essentially a
      linear learning problem, which significantly reduces the computational burden.
      Numerous applications show that such a computation burden reduction does not
      degrade the generalization capability. It has, however, been open that whether
      this is true in theory. The aim of this paper is to study the theoretical
      feasibility of ELM by analyzing the pros and cons of ELM. In the previous part of
      this topic, we pointed out that via appropriately selected activation functions,
      ELM does not degrade the generalization capability in the sense of expectation.
      In this paper, we launch the study in a different direction and show that the
      randomness of ELM also leads to certain negative consequences. On one hand, we
      find that the randomness causes an additional uncertainty problem of ELM, both in
      approximation and learning. On the other hand, we theoretically justify that
      there also exist activation functions such that the corresponding ELM degrades
      the generalization capability. In particular, we prove that the generalization
      capability of ELM with Gaussian kernel is essentially worse than that of FNN with
      Gaussian kernel. To facilitate the use of ELM, we also provide a remedy to such a
      degradation. We find that the well-developed coefficient regularization technique
      can essentially improve the generalization capability. The obtained results
      reveal the essential characteristic of ELM in a certain sense and give
      theoretical guidance concerning how to use ELM. 

PMID- 25069129
TI  - Signal-quality indices for the electrocardiogram and photoplethysmogram:
      derivation and applications to wireless monitoring.
AB  - The identification of invalid data in recordings obtained using wearable sensors
      is of particular importance since data obtained from mobile patients is, in
      general, noisier than data obtained from nonmobile patients. In this paper, we
      present a signal quality index (SQI), which is intended to assess whether
      reliable heart rates (HRs) can be obtained from electrocardiogram (ECG) and
      photoplethysmogram (PPG) signals collected using wearable sensors. The algorithms
      were validated on manually labeled data. Sensitivities and specificities of 94%
      and 97% were achieved for the ECG and 91% and 95% for the PPG. Additionally, we
      propose two applications of the SQI. First, we demonstrate that, by using the SQI
      as a trigger for a power-saving strategy, it is possible to reduce the recording
      time by up to 94% for the ECG and 93% for the PPG with only minimal loss of valid
      vital-sign data. Second, we demonstrate how an SQI can be used to reduce the
      error in the estimation of respiratory rate (RR) from the PPG. The performance of
      the two applications was assessed on data collected from a clinical study on
      hospital patients who were able to walk unassisted. 

PMID- 25069130
TI  - Inverse estimation of multiple muscle activations from joint moment with muscle
      synergy extraction.
AB  - Human movement is produced resulting from synergetic combinations of multiple
      muscle contractions. The resultant joint movement can be estimated through the
      related multiple-muscle activities, which is formulated as the forward problem.
      Neuroprosthetic applications may benefit from cocontraction of agonist and
      antagonist muscle pairs to achieve more stable and robust joint movements. It is
      necessary to estimate the activation of each individual muscle from desired joint
      torque(s), which is the inverse problem. A synergy-based solution is presented
      for the inverse estimation of multiple muscle activations from joint movement,
      focusing on one degree-of-freedom tasks. The approach comprises muscle synergy
      extraction via the nonnegative matrix factorization algorithm. Cross validation
      is performed to evaluate the method for prediction accuracy based on experimental
      data from ten able-bodied subjects. The results demonstrate that the approach
      succeeds to inversely estimate the multiple muscle activities from the given
      joint torque sequence. In addition, the other one's averaged synergy ratio was
      applied for muscle activation estimation with leave-one-out cross-validation
      manner, which resulted in 9.3% estimation error over all the subjects. The
      obtained results support the common muscle synergy-based neuroprosthetics control
      concept.

PMID- 25069131
TI  - Performance-power consumption tradeoff in wearable epilepsy monitoring systems.
AB  - Automated seizure detection methods can be used to reduce time and costs
      associated with analyzing large volumes of ambulatory EEG recordings. These
      methods however have to rely on very complex, power hungry algorithms,
      implemented on the system backend, in order to achieve acceptable levels of
      accuracy. In size, and therefore power-constrained EEG systems, an alternative
      approach to the problem of data reduction is online data selection, in which
      simpler algorithms select potential epileptiform activity for discontinuous
      recording but accurate analysis is still left to a medical practitioner. Such a
      diagnostic decision support system would still provide doctors with information
      relevant for diagnosis while reducing the time taken to analyze the EEG. For
      wearable systems with limited power budgets, data selection algorithm must be of
      sufficiently low complexity in order to reduce the amount of data transmitted and
      the overall power consumption. In this paper, we present a low-power hardware
      implementation of an online epileptic seizure data selection algorithm with
      encryption and data transmission and demonstrate the tradeoffs between its
      accuracy and the overall system power consumption. We demonstrate that overall
      power savings by data selection can be achieved by transmitting less than 40% of
      the data. We also show a 29% power reduction when selecting and transmitting 94%
      of all seizure events and only 10% of background EEG. 

PMID- 25069132
TI  - Collaborative fuzzy clustering from multiple weighted views.
AB  - Clustering with multiview data is becoming a hot topic in data mining, pattern
      recognition, and machine learning. In order to realize an effective multiview
      clustering, two issues must be addressed, namely, how to combine the clustering
      result from each view and how to identify the importance of each view. In this
      paper, based on a newly proposed objective function which explicitly incorporates
      two penalty terms, a basic multiview fuzzy clustering algorithm, called
      collaborative fuzzy c-means (Co-FCM), is firstly proposed. It is then extended
      into its weighted view version, called weighted view collaborative fuzzy c-means
      (WV-Co-FCM), by identifying the importance of each view. The WV-Co-FCM algorithm
      indeed tackles the above two issues simultaneously. Its relationship with the
      latest multiview fuzzy clustering algorithm Collaborative Fuzzy K-Means (Co-FKM)
      is also revealed. Extensive experimental results on various multiview datasets
      indicate that the proposed WV-Co-FCM algorithm outperforms or is at least
      comparable to the existing state-of-the-art multitask and multiview clustering
      algorithms and the importance of different views of the datasets can be
      effectively identified. 

PMID- 25069133
TI  - Real-time human movement retrieval and assessment with Kinect sensor.
AB  - The difficulty of vision-based posture estimation is greatly decreased with the
      aid of commercial depth camera, such as Microsoft Kinect. However, there is still
      much to do to bridge the results of human posture estimation and the
      understanding of human movements. Human movement assessment is an important
      technique for exercise learning in the field of healthcare. In this paper, we
      propose an action tutor system which enables the user to interactively retrieve a
      learning exemplar of the target action movement and to immediately acquire motion
      instructions while learning it in front of the Kinect. The proposed system is
      composed of two stages. In the retrieval stage, nonlinear time warping algorithms
      are designed to retrieve video segments similar to the query movement roughly
      performed by the user. In the learning stage, the user learns according to the
      selected video exemplar, and the motion assessment including both static and
      dynamic differences is presented to the user in a more effective and organized
      way, helping him/her to perform the action movement correctly. The experiments
      are conducted on the videos of ten action types, and the results show that the
      proposed human action descriptor is representative for action video retrieval and
      the tutor system can effectively help the user while learning action movements. 

PMID- 25069134
TI  - Tradeoffs between trust and survivability for mission effectiveness in tactical
      networks.
AB  - In a military tactical network, maintaining trust among members in a mission
      group is critical to successful mission completion. However, maintaining high
      trust among group members in a resource-restricted tactical environment
      detrimentally reduces system lifetime, which may lead to mission failure or low
      mission effectiveness. In this paper, we aim to investigate the relationships
      between group trust and system lifetime [i.e., survivability measuring mean time
      to mission failure (MTTMF)] and to capture mission effectiveness achieved by the
      mission group based on the tradeoff between these two goals. We employ a
      composite trust capturing various angles of trust concept derived from
      communication, information, and social networks. We take a game theoretic
      approach using the so called Aoyagi's game theory, enforcing nodes to exhibit
      desirable behavior based on reward or penalty given by the system. In designing
      reward/penalty mechanisms, we adopt the concept of aspiration level, defining
      success or failure based on a goal set by the system, and prove there exists an
      optimal trust threshold maximizing both MTTMF (i.e., system
      lifetime/survivability) and group trust. We devised a mission effectiveness
      metric based on both the metrics having conflicting goals. We developed an
      analytical model using Stochastic Petri Nets, and validated the analytical
      results with simulation results. We conducted comparative performance analyzes of
      the variations of the proposed scheme with respect to a node's decision nature
      (i.e., rational versus altruistic) and trust threshold policy (static versus
      dynamic) in resource-constrained tactical environments. 

PMID- 25069135
TI  - Consistency-driven automatic methodology to set interval numerical scales of 2
      tuple linguistic term sets and its use in the linguistic GDM with preference
      relation.
AB  - The 2-tuple linguistic modeling is a popular tool for computing with words in
      decision making. In order to deal with the linguistic term sets that are not
      uniformly and symmetrically distributed, the numerical scale model has been
      developed to generalize the 2-tuple linguistic modeling. In the numerical scale
      model, the key task of the 2-tuple based models is the definition of a numerical
      scale function that establishes a one to one mapping between the linguistic
      information and numerical values. In this paper, we propose a consistency-driven
      automatic methodology to set interval numerical scales of 2-tuple linguistic term
      sets in the decision making problems with linguistic preference relations. This
      consistency-driven methodology is based on a natural premise regarding the
      consistency of preference relations. If linguistic preference relations provided
      by experts are of acceptable consistency, the corresponding transformed numerical
      preference relations by the established interval numerical scale are also
      consistent. Compared with the existing approach based on canonical characteristic
      values, the consistency-driven methodology provides a new way to set the interval
      numerical scale without the need of the semantics defined by interval type-2
      fuzzy sets. Meanwhile, interval multiplicative preference relations are used in
      the pairwise comparisons method and the presented theory can be utilized in the
      pairwise comparisons method as it provides a novel approach to automatic
      construct interval multiplicative preference relations. Finally, we present the
      framework for the use of the consistency-driven automatic methodology in
      linguistic group decision making problems and two numerical examples are given to
      illustrate the feasibility and validity of this proposal. 

PMID- 25069136
TI  - Improved hybrid optimization algorithm for 3D protein structure prediction.
AB  - A new improved hybrid optimization algorithm - PGATS algorithm, which is based on
      toy off-lattice model, is presented for dealing with three-dimensional protein
      structure prediction problems. The algorithm combines the particle swarm
      optimization (PSO), genetic algorithm (GA), and tabu search (TS) algorithms.
      Otherwise, we also take some different improved strategies. The factor of
      stochastic disturbance is joined in the particle swarm optimization to improve
      the search ability; the operations of crossover and mutation that are in the
      genetic algorithm are changed to a kind of random liner method; at last tabu
      search algorithm is improved by appending a mutation operator. Through the
      combination of a variety of strategies and algorithms, the protein structure
      prediction (PSP) in a 3D off-lattice model is achieved. The PSP problem is an NP
      hard problem, but the problem can be attributed to a global optimization problem
      of multi-extremum and multi-parameters. This is the theoretical principle of the
      hybrid optimization algorithm that is proposed in this paper. The algorithm
      combines local search and global search, which overcomes the shortcoming of a
      single algorithm, giving full play to the advantage of each algorithm. In the
      current universal standard sequences, Fibonacci sequences and real protein
      sequences are certified. Experiments show that the proposed new method
      outperforms single algorithms on the accuracy of calculating the protein sequence
      energy value, which is proved to be an effective way to predict the structure of
      proteins.

PMID- 25069137
TI  - A DFT study on the adsorption of benzodiazepines to vermiculite surfaces.
AB  - Widespread use of pharmaceuticals such as benzodiazepines has been resulting over
      the last decades in the dissemination of residues of these compounds in the
      environment, and such fact has been raising increasing concern. The generally low
      efficiencies of conventional wastewater treatment processes for the removal of
      this type of pollutants demands for the development of alternative or
      complementary water and wastewater treatment technologies, among which adsorption
      processes have been gaining popularity, provided that cheap efficient adsorbents
      are found. Clay materials have been one of the popular choices in this regard. In
      the present study, quantum chemical calculations have been performed by periodic
      DFT using the projector augmented-wave (PAW) method to characterize the
      interactions of two benzodiazepine molecules, alprazolam and diazepam, with a
      surface of clay mineral, vermiculite. It was observed that both molecules
      interact strongly with the vermiculite surface, both through a water-bridge
      binding and by cation-bridge provided by the exchangeable Mg(2+) cations of the
      vermiculite surface. The results point to an interesting potential of vermiculite
      to be used efficiently as filter medium to remove these pollutants from water and
      wastewater.

PMID- 25069138
TI  - Evaluation of the antiradical activity of hyperjovinol-A utilizing donor-acceptor
      maps.
AB  - Hyperjovinol-A ((2-methyl-1-(2,4,6-trihydroxy-3-(3-hydroxy-3,7-dimethyloct-6
      enyl)phen yl)propan-1-one) is an acylated phloroglucinol isolated from Hypericum
      Jovis and exhibiting good antioxidant activity. The study investigates the
      compound's antiradical ability on the basis of the electron-donor and electron
      acceptor abilities of its conformers, deriving donor and acceptor indexes and
      mapping them in terms of donor-acceptor maps (DAM). The DAMs of vitamins C and E
      and of carotene astaxantine are used as comparison references. Calculations were
      performed at the DFT/BPW91/6-311+G(d,p) level, with optimizations on fully
      relaxed geometries to obtain the conformers of the neutral molecule in vacuo, and
      single point calculations to obtain the energies of the cationic and anionic
      species in vacuo and of the neutral, cationic, and anionic species in water,
      ethanol, and pentylethanoate. The calculations in solution utilized the
      polarizable continuum model (PCM). The results indicate that hyperjovinol-A may
      have better antiradical activity than vitamin C. This is in agreement with
      experimental results, showing that the antioxidant activity of hyperjovinol-A is
      comparable with that of the best drugs currently in clinical use. The activity is
      maintained in solution. The Fukui function f(.) was also calculated for all the
      conformers of hyperjovinol-A, to identify the regions of highest reactivity.

PMID- 25069139
TI  - Why is it taking so long for healthcare professional education to become relevant
      and effective? What can be done?
AB  - For about a half century the World Health Organization (WHO), supported by the
      literature in the field of health personnel education, has argued for the
      benefits of a learner-centered and community-oriented approach to professional
      education. Nevertheless, change has not happened in the vast majority of schools
      and countries. This paper describes the obstacles and constraints to change in
      health professional education: Obsolete administrative rules, the low profile of
      public health, the lack of real decision power of faculty, a dearth of faculty
      trained in the field of education, the arbitrary separation between so-called
      basic sciences and clinical practice, the disciplinary orientation of learning
      objectives, a lack of explicit definition of desirable professional competencies,
      and, above all, too little value placed on the evaluation of educational
      programs. The recent literature continues to argue for change but action does not
      follow. Only very few training institutions currently put newer approaches into
      practice. The university culture remains an environment that stifles change.

PMID- 25069140
TI  - [Erdheim-Chester disease-the rare and under-diagnosed disease-editorial].

PMID- 25069141
TI  - [Closed pleural biopsy in the diagnostics of malignant pleural involvement
      editorial].

PMID- 25069142
TI  - [Impact of natriuretic peptides in current clinical practice-editorial].

PMID- 25069143
TI  - [Sentinel biopsy, a short outline-editorial].

PMID- 25069144
TI  - Psychological intimate partner violence during pregnancy and birth outcomes:
      threat of violence versus other verbal and emotional abuse.
AB  - Although physical abuse during pregnancy has been linked to poor birth outcomes,
      the role of psychological abuse is less well understood. Associations between
      birth outcomes and types of psychological abuse during pregnancy (being
      threatened, screamed at, or insulted) were examined in 489 women with no history
      of physical abuse. Being threatened was significantly associated with adverse
      birth outcomes, with women reporting any instance during pregnancy twice as
      likely to deliver a low birth weight baby. These results remained after
      controlling for background factors. Finally, most of the variance between threats
      and birth weight was accounted for by mediating health behaviors (specifically
      prenatal care utilization and pregnancy weight gain), suggesting pathways for the
      negative effects of being threatened by an intimate partner during pregnancy.

PMID- 25069145
TI  - Adolescents who assault their parents:a different family profile of young
      offenders?
AB  - Some authors have proposed that the mechanisms underlying adolescent-to-parent
      abuse seem to be different from other forms of juvenile delinquency. Given that
      this aggression is exerted within the family setting, our study was aimed to
      explore if there was a differential family profile for those adolescents who
      commit a parent abuse offense compared to those who commit other types of
      offenses. Judicial files of 1,046 young offenders from the Juvenile Justice
      Service of Jaen (Spain) were examined. The final sample (654 young offenders) was
      divided into 2 groups: those who had committed offenses against a parent (parent
      abuse group) and those who had committed other types of offenses (other offenses
      group). Results showed that families with parent abuse have differential
      characteristics, especially regarding the family size, type of household,
      parenting styles, and the patterns of interactions between the family members.

PMID- 25069146
TI  - The experiences of homicide victims' families with the criminal justice system:
      an exploratory study.
AB  - Although the crime of homicide has received significant attention from scholars,
      little research exists that examines the impact of homicide on surviving family
      members. Because opportunities for victims and family members of victims to
      participate in the criminal justice system are increasing, it is important to
      understand the impact of these forms of participation on those who choose to
      participate. This study uses data from focus groups to examine the experiences of
      homicide survivors within the criminal justice system, including views about how
      system involvement and specific outcomes (i.e., sentencing) may help or hinder
      healing. Findings suggest that many families leave the criminal justice system
      feeling marginalized and revictimized. This study calls into question the current
      criminal justice system's ability to meet the needs of crime victim and their
      families.

PMID- 25069148
TI  - Sexual orientation, child abuse, and intimate partner violence victimization.
AB  - Research has consistently found rates of intimate partner violence (IPV) in
      nonheterosexual relationships to be comparable or higher than rates of IPV in
      heterosexual relationship. Less is understood about the relationship between
      child abuse, sexual orientation, and IPV victimization. The role of sexual
      orientation in the relationship between child abuse and IPV victimization is
      important to consider given research has found higher rates of childhood abuse
      among nonheterosexual individuals. In addition, the relationship between child
      abuse victimization and IPV victimization in adulthood has also been documented.
      This research extends the literature on IPV by comparing child abuse
      victimization as a predictor for IPV between heterosexual and nonheterosexual IPV
      victims. Using the National Violence Against Women Survey, this study used
      logistic regression models to find partial support for the hypothesis that
      nonheterosexuals who experience child abuse will be more likely to be IPV victims
      as adults than similarly situated heterosexuals.

PMID- 25069147
TI  - Antecedents of intimate partner violence among gay and bisexual men.
AB  - Examinations of gay and bisexual men's (GBM) perceptions of intimate partner
      violence (IPV), including their perceptions of events likely to precipitate IPV,
      are lacking. Focus group discussions with GBM (n = 83) yielded 24 unique
      antecedents, or triggers, of IPV in male-male relationships. Venue-recruited
      survey participants (n = 700) identified antecedents that were likely to cause
      partner violence in male-male relationships, including antecedents GBM-specific
      currently absent from the literature. Chi-square tests found significant
      variations in antecedent endorsement when tested against recent receipt of IPV.
      Linear regression confirmed that men reporting recent IPV endorsed significantly
      more IPV antecedents than men without recent IPV (beta = 1.8155, p < .012). A
      better understanding of the IPV event itself in male-male couples versus
      heterosexual couples, including its antecedents, can inform and strengthen IPV
      prevention efforts.

PMID- 25069149
TI  - Associations between intimate partner violence and posttraumatic stress symptom
      severity in a multiethnic sample of men with histories of childhood sexual abuse.
AB  - OBJECTIVE: Little research exists identifying risk factors for posttraumatic
      stress symptoms (PTSS) among men with histories of childhood sexual abuse (CSA)
      who have been exposed to intimate partner violence (IPV). METHODS: One hundred
      and fifty African American, Latino and non-Latino White men with histories of CSA
      participated in this study. RESULTS: An ordinary least squares regression model
      with race/ethnicity, HIV serostatus, and CSA severity treated as cofounders and
      with IPV as the predictor was fitted to predict level of PTSS. Higher levels of
      IPV were significantly associated with higher PTSS, as were higher levels of
      chronic stress, and being African American. CONCLUSIONS: Mental health service
      providers should routinely screen for IPV in men who report histories of CSA and
      PTSS.

PMID- 25069150
TI  - Control and support models of help-seeking behavior in women experiencing
      domestic violence in India.
AB  - In India, there is limited prioritization of domestic violence, which is seen as
      a private and family matter, and handled as a social responsibility rather than a
      complaint or crime. Despite the Domestic Violence Act, implemented in 2006, the
      widespread phenomenon of domestic violence across Indian states goes unreported.
      Using control and support models, this article aims to examine women's behavior
      in seeking help while dealing with partner violence. It is a population-based
      analytical cross-sectional study covering 14,507 married women from 18 states of
      India, selected through a systematic multistage sampling strategy. Both
      quantitative and qualitative methods were used to generate data. It was observed
      that legal complexities combined with social realities make the life of an
      average Indian woman insecure and miserable. Most women surveyed preferred the
      social-support model and opined that if they face domestic violence, they would
      seek help from their parents as the first option in the order of preference. The
      responses of women while dealing with domestic violence are often spontaneous and
      determined by the pressing need to resolve matters within the home/community,
      rather than addressing them in the public domain of state institutions where
      procedures are cumbersome and lengthy. A new integrated development model
      proposed by several communities aims to prevent domestic violence through the
      intervention of health care systems.

PMID- 25069151
TI  - Psychosocial support for trauma-affected students after school shootings in
      Finland.
AB  - In Finland, as many as 20 people have lost their lives in two school shootings
      within one year. This article describes trauma-theoretical rationale, planning,
      and implementation of acute and long-term psychosocial aftercare that was
      organized in Kauhajoki where one of the school shootings happened. The aftercare
      was embedded in the school community's everyday life to enhance easy access. The
      aftercare proceeded in 6 phases, involving the immediate support phase at the
      first 24 hr, the acute phase for the first 2 weeks, followed by a 5-month period
      of empowerment, normalization, and creating "a safe place." The habituation phase
      coincided with the completion of the renovation of the damaged school building
      and students returning to the scene. The first anniversary was marked by shared
      rituals and remembrance, and the follow-up phase lasted until the end of the
      aftercare in 2 years. The aftercare contained, for example, psychoeducation,
      screening, and services at community, group, and individual levels.

PMID- 25069153
TI  - Getting by after a loved one's death by homicide: the relationship between case
      status, trauma symptoms, life satisfaction, and coping.
AB  - Covictims of homicide are the loved ones of people killed by homicide. As
      secondary victims, they experience trauma from the crime yet are not the focus of
      criminal justice system (CJS) processes. The current descriptive-exploratory
      study seeks to better understand this often hidden population by exploring the
      relationship between CJS case status, trauma symptoms, life satisfaction, and
      coping with a group of 137 covictims from the Mid-South region of the United
      States. Findings indicate that case closure does not resolve trauma symptoms,
      although symptoms do lessen. In addition, a broad range of helping services and
      coping strategies are used after the homicide. Some are associated with CJS case
      status, trauma symptoms, and life satisfaction whereas others are not. These
      findings highlight important areas for future research.

PMID- 25069152
TI  - The role of alcohol use during sexual situations in the relationship between
      sexual revictimization and women's intentions to engage in unprotected sex.
AB  - Research has demonstrated relationships among childhood sexual abuse, adult
      sexual assault, and sexual risk taking. This study proposes that one mechanism
      through which the victimization-sexual risk-taking relationship works is through
      an increased likelihood of drinking during sexual situations. Using path
      analysis, this study explores this hypothesis in a sample of 230 women. The model
      illustrates that women with a history of child and adult sexual victimization
      reported greater intentions to engage in unprotected sex and that this
      relationship is in part accounted for by an increased likelihood of drinking in
      sexual situations. The results suggest that sexual risk reduction programs and
      sexual assault treatment programs should educate women about the alcohol-involved
      sexual risk taking that often follows sexual assault victimization.

PMID- 25069154
TI  - My brother's reaper: examining officially reported siblicide incidents in the
      United States, 2000-2007.
AB  - With higher rates than any other form of intrafamilial violence, Hoffman and
      Edwards (2004) note, sibling violence "constitutes a pandemic form of
      victimization of children, with the symptoms often going unrecognized and the
      effect ignored" (p. 187). Approximately 80% of children reside with at least one
      sibling (Kreider, 2008), and in its most extreme form sibling violence manifests
      as siblicide. Siblicide is poorly understood with fewer than 20 empirical studies
      identified in the extant literature since 1980 (see Eriksen & Jensen, 2006). The
      present work employs 8 years of Supplemental Homicide Report (SHR) data, 2000
      2007, with siblicide victims and offenders age 21 years and younger, to construct
      contemporary victim and offender profiles examining incident characteristics.
      Findings highlight the sex-based nature of the offense with unique victimization
      patterns across victims and offenders. Older brothers using a firearm are the
      most frequent offenders against both male and female siblings. Strain as a
      theoretical foundation of siblicide is offered as an avenue for future inquiry.

PMID- 25069155
TI  - Chemical constituents of Croton oligandrum (Euphorbiaceae).
AB  - A new clerodane diterpene derivative named crotonoligaketone was obtained from
      the stem bark of Croton oligandrum along with eight known compounds including
      crotonadiol, imbricatadiol, crotonzambefuran B, 7-acetoxytrachiloban-18-oic acid,
      3-O-acetylaleuritolic acid, lupeol, beta-sitosterol, and stigmasterol. The
      structures of the isolated compounds were established on the basis of their
      spectral data and by comparison with those reported in the literature.

PMID- 25069156
TI  - Acacetin-7-rutinoside from Buddleja lindleyana, a new molluscicidal agent against
      Oncomelania hupensis.
AB  - Buddleja lindleyana is a medicinally important member of the family Loganiaceae
      distributed in Eastern China. The plant has been used in different traditional
      medications for the treatment of various diseases. Acacetin-7-rutinoside was
      isolated from the n-butanol fraction of fresh B. lindleyana leaves and found to
      be a new molluscicidal agent against the snail Oncomelania hupensis. The
      structure of acacetin-7-rutinoside was elucidated based on spectral data,
      including 1H NMR and 13C NMR.

PMID- 25069157
TI  - Cytotoxic saponins from the seeds of Pittosporum angustifolium.
AB  - Three new acylated R1-barrigenol triterpene glycosides, 1-3, were isolated from
      the seeds of Pittosporum angustifolium Lodd. together with four known glycosides,
      4-7, containing R1- and A1-barrigenol backbones. On the basis of spectroscopic,
      spectrometric, and chemical analyses the novel compounds were named
      pittangretosides N-P and established as 21beta-acetoxy-22alpha-angeloyloxy- (1),
      21beta-acetoxy-22alpha-(2-acetoxy-2-methylbutyroyloxy)- (2), and 21beta-(2
      methylbutyroyloxy)-22alpha-acetoxy-3beta-[beta-D-glucopyranosyl- (1 --> 2)]
      [alpha-L-arabinopyranosyl-(1 --> 3)]-[alpha-L-arabinofuranosyl-(1 --> 4)]-beta-D
      glucuronopyranosyloxyolean-12-ene-15alpha, 6alpha, 28-triol (3). Evaluation of
      the in vitro cytotoxicity against three tumour cell lines and one non
      tumourigenic cell line revealed antiproliferative effects with IC50 values in a
      range of 1.74-34.1 microM.

PMID- 25069158
TI  - Flavone composition and antihypercholesterolemic and antihyperglycemic activities
      of Chrysanthemum coronarium L.
AB  - Five flavones were isolated from Chrysanthemum coronarium L., four of which were
      isolated for the first time from the genus Chrysanthemum. Two were the flavonoid
      aglycones 5,7-dihydroxy-3,6,4'-trimethoxyflavone (1) and scutellarin-6,7-dimethyl
      ether (2). A new flavonoid glycoside, apigenin-7-O-[2"(6'''-O-beta-D
      acetylglucopyranosyl)]-6"-O-acetylglucopyranoside (3), along with two known ones,
      i. e. apigenin-7-O-(2"-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside (4) and 6
      methoxy quercetin-7-O-beta-D-glucopyranoside (5), were identified. Structures
      were elucidated by NMR and MS. The therapeutic value of petroleum ether, ethyl
      acetate, and methanol extracts, respectively, in rats suffering from
      hypercholesterolemia--as a consequence of high-fat diet-and hyperglycemia--as a
      consequence of hypercholesterolemia and low doses of streptozotocin--was
      investigated through determination of biochemical markers and histopathology. The
      ethyl acetate and methanol extracts showed remarkable results, followed by the
      petroleum ether extract.

PMID- 25069159
TI  - New nitrogenous compounds from Anisotes trisulcus.
AB  - Re-investigation of the methanolic extract of Anisotes trisulcus (Forssk.) Nees
      aerial parts led to the isolation of two new tricyclic quinazoline alkaloids, 8
      amino-7,8,9,11-tetrahydro-6H-pyrido[2,1-b]-quinazoline-2,6-diol (4) and 8-amino
      3,6-dihydroxy-7,8,9-trihydro-6H-pyrido[2,1-b]quinazoline-11-one (5), and two
      quaternary ammonium compounds, (dimethylamino)-N-(hydroxymethyl)-N,N-dimethyl
      methanaminium chloride (6) and N-[(carboxyamino)methyl]-N,N-dimethyl ethanaminium
      chloride (7), together with three known compounds, peganine (1), vasicinone (2),
      and anisotine (3). The structures of these compounds were established on the
      basis of physical, chemical, and spectral data (UV, IR, MS, 1D and 2D NMR), as
      well as by comparison with authentic samples. GC-MS analysis of the fatty acid
      methyl esters and unsaponifiable matter revealed the presence of 46 fatty acids,
      53 hydrocarbons, and 18 sterols. The different extracts were evaluated for their
      antihyperglycaemic activities. The MeOH, n-hexane, and EtOAc extracts exhibited a
      significant hypoglycaemic effect.

PMID- 25069160
TI  - Inhibitory effect of the methanolic extract of Verbascum latisepalum Hub.-Mor. on
      endothelium-dependent relaxation in rat thoracic aorta.
AB  - The leaves and flowers of Verbascum species are used to treat respiratory
      disorders, haemorrhoids, rheumatic pain, and wounds as well as for the treatment
      of eczema and other types of inflammatory skin conditions in traditional Turkish
      medicine. We examined the effect of the methanolic extract of the aerial parts of
      Verbascum latisepalum Hub.-Mor. on the endothelium-dependent relaxation response
      in rat aortic rings which is mediated by nitric oxide (NO). Six fractions, A-F,
      were obtained from the methanolic extract through bioassay-guided fractionation
      procedures. The phenylethanoid glycoside verbascoside was isolated from fraction
      D and its structure elucidated by spectral techniques. The inhibitory effects of
      the extract, its fractions, and verbascoside on the acetylcholine-induced
      relaxation response in phenylephrine-precontracted aorta was examined in the
      absence and presence of L-arginine, a precursor in the synthesis of NO. The
      observation that the effects of the methanolic extract, of fraction D, and of
      verbascoside were reversed by L-arginine, indicates that verbascoside has an
      inhibitory effect on the synthesis of NO. This effect should be taken into
      consideration in view of the wide range of uses of Verbascum species in Turkish
      folk medicine.

PMID- 25069161
TI  - Exogenous ascorbic acid and glutathione alleviate oxidative stress induced by
      salt stress in the chloroplasts of Oryza sativa L.
AB  - The effects of exogenous ascorbic acid (AsA) and reduced glutathione (GSH) on
      antioxidant enzyme activities [superoxide dismutase (SOD), ascorbate peroxidase
      (APX), and glutathione reductase (GR)] and the contents of malondialdehyde (MDA)
      and H2O2, as well as of endogenous AsA and GSH, in the chloroplasts of two rice
      cultivars, the salt-tolerant cultivar Pokkali and the salt-sensitive cultivar
      Peta, were investigated. Exogenous AsA and GSH enhanced SOD, APX, and GR
      activities, increased endogenous AsA and GSH contents, and reduced those of H2O2
      and MDA in the chloroplasts of both cultivars under salt stress (200 mM NaCl),
      but the effects were significantly more pronounced in cv. Pokkali. GSH acted more
      strongly than AsA on the plastidial reactive oxygen scavenging systems. These
      results indicated that exogenous AsA and GSH differentially enhanced salinity
      tolerance and alleviated salinity-induced damage in the two rice cultivars.

PMID- 25069162
TI  - Improved beta-carotene and lycopene production by Blakeslea trispora with
      ultrasonic treatment in submerged fermentation.
AB  - Response surface methodology (RSM) based on Box-Behnken design (BBD) was employed
      to investigate the effect of ultrasonic treatment on beta-carotene production by
      Blakeslea trispora. The optimized strategy involved exposing three-day-old
      mycelial cultures to ultrasonic treatment at a fixed frequency of 20 kHz, power
      of 491 W, treatment time of 3 min, working time of 3 s, and rest time of 5.8 s,
      repeated four times at a 24-h interval. Mycelium growth was not significantly
      promoted under ultrasonic stimulation; however, the glucose metabolism increased
      by about 10%, the average size of the aggregates significantly decreased, and the
      uptake rate of imidazole into cells was increased about 2.5-fold. After a 6-d
      culture, the technique produced 173 mg/L of beta-carotene and 82 mg/L of
      lycopene, which represented an increase of nearly 40.7% and 52.7%, respectively,
      over the yields obtained in cultures without ultrasonic treatment.

PMID- 25069163
TI  - Microbial metabolism of danazol: a contribution to doping analysis.
AB  - Microbial metabolism of danazol (17alpha-pregna-2,4-dien-20-yno[2,3-d]isoxazol
      17beta-ol) by Beauveria bassiana ATCC 7159 and Glyocladium viride ATCC 10097
      afforded four metabolites. The isolated metabolites were identified by different
      spectroscopic techniques as 6beta-hydroxy danazol, which is a not yet reported
      danazol metabolite, 17beta-hydroxy-17alpha-pregn-4-en-20-yn-3-one (ethisterone)
      and 17beta-hydroxy-2alpha-(hydroxymethyl)-17alpha-pregn-4-en-20-yn-3-one (2alpha
      hydroxymethyl ethisterone), which represent the major danazol metabolites
      detected in human urine. The last metabolite, 6beta,17beta-dihydroxy-2
      (hydroxymethyl)-17alpha-pregna-1,4-dien-20-yn-3-one, is also a minor human
      metabolite, for which the NMR data are described here for the first time. The
      metabolites were isolated in quantities that allowed their use for direct
      comparison in routine doping analysis.

PMID- 25069164
TI  - Identification of two chemotypes of Pogostemon cablin (Blanco) Benth. through DNA
      barcodes.
AB  - Pogostemon cablin (Blanco) Benth. is an important medicinal plant in Traditional
      Chinese Medicine (TCM). Because of differences in the chemical composition, this
      species has been classified into two major chemotypes, i. e. the patchouliol-type
      and the pogostone-type; however, no quick and effective method is presently
      available for the precise identification of these two chemotypes. DNA barcoding,
      using a standardized DNA fragment, is a promising molecular diagnostic method for
      species identification. We have established a reliable and quick method for the
      identification of the P. cablin chemotypes. Of five potential barcodes [rbcL,
      psbA-trnH, rpoB, ITS (internal transcibed spacer), and ndhJ], tested among 103
      samples, ITS was the best candidate, as comparative studies between patchouliol
      type and pogostone-type P. cablin revealed that ITS had more variable regions
      among these five barcodes. We suggest that ITS can serve as the most suitable
      barcode for differentiating between the chemotypes of P. cablin.

PMID- 25069166
TI  - Women leading the way.

PMID- 25069165
TI  - cDNA cloning and expression analysis of farnesyl pyrophosphate synthase from
      Ornithogalum saundersiae.
AB  - Farnesyl pyrophosphate synthase (FPPS, EC 2.5.1.10) catalyzes the consecutive
      head-to-tail condensations of isopentenyl diphosphate (IPP) with dimethylallyl
      diphosphate (DMAPP) to form farnesyl pyrophosphate (FPP), a key precursor of
      sesquiterpenoids, triterpenoids, sterols, and farnesylated proteins. Here we
      report the molecular cloning and functional identification of a new full-length
      cDNA encoding FPPS from Ornithogalum saundersiae, a potential medicinal plant
      that produces a promising antitumour sterol glycoside, OSW-1. An 1327 bp long
      unigene with an open reading frame of 1044 bp was retrieved from the
      transcriptome sequencing of O. saundersiae. The full-length FPPS cDNA, designated
      OsaFPPS, was isolated from O. saundersiae with gene-specific primers. The
      resultant OsaFPPS encodes a 347-amino acids protein with a calculated molecular
      mass of 40,085.6 Da, and a theoretical isoelectric point of 5.01. Phylogenetic
      tree analysis indicated that OsaFPPS belongs to the plant FPPS super-family.
      Expression of soluble OsaFPPS in E. coli was verified by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis.
      Functional analysis of the purified OsaFPPS protein was carried out using IPP and
      DMAPP as substrates, and the product was unambiguously determined by gas
      chromatography-mass spectrometry (GC-MS) analyses.

PMID- 25069167
TI  - Plans to deregulate migration arrangements threatens grads.

PMID- 25069168
TI  - The responsibility of care. A conversation about the registered nurse's role.

PMID- 25069169
TI  - Learning from clinical leaders.

PMID- 25069170
TI  - Preventing ethical conflicts.

PMID- 25069171
TI  - Developing a protocol for people living with HIV entering residential aged care
      facilities.

PMID- 25069172
TI  - Kieran's story.

PMID- 25069173
TI  - StARTalking.

PMID- 25069174
TI  - A mental health issue that does not discriminate.

PMID- 25069175
TI  - Adopting the Team Leader Model of student supervision into the acute mental
      health setting.

PMID- 25069176
TI  - Positive changes in mental health.

PMID- 25069177
TI  - New ways to enhance mental health nursing: collaboration between academy and
      practice.

PMID- 25069178
TI  - Keeping the body in mind.

PMID- 25069179
TI  - The Productive Ward in an over productive environment.

PMID- 25069180
TI  - The alcohol smoking and substance involvement screening test in an acute mental
      health setting.

PMID- 25069181
TI  - Improving continence management of long stay mental health populations.

PMID- 25069182
TI  - Youth to benefit from Fiona Stanley Hospital mental health service.

PMID- 25069183
TI  - Hospitality in mental health nursing.

PMID- 25069184
TI  - Open borders.

PMID- 25069185
TI  - A specialist nurse role improves nurse the physical health behaviours of mental
      health consumers.

PMID- 25069186
TI  - Nurse professionals viable in mental health care.

PMID- 25069187
TI  - CQUniversity leads innovation in mental health nursing.

PMID- 25069188
TI  - Caring about the unbefriended elderly.

PMID- 25069189
TI  - Antibiotic overuse.

PMID- 25069190
TI  - Putting theory into practice.

PMID- 25069191
TI  - [Influence of acupuncture of "Changqiang" (GV 1) on learning-memory ability and
      gap junction-related protein expression in the prefrontal cortex in autism rats].
AB  - OBJECTIVE: To observe the effect of acupuncture stimulation of "Changqiang" (GV
      1) on learning-memory ability and gap junction-related protein expression in the
      prefrontal cortex in autism rats. METHODS: Forty Wistar rats were equally
      randomized into control, model, GV 1 and non-acupoint groups. For establishing
      autism model, Valproate acid (VPA) sodium (600 mg/kg) was given (i. p.) to
      pregnancy rats whose intimate filial generation was confirmed to be successful
      autism by eye-open tests, swimming test and Morris water maze swimming tasks. GV
      1 or non-acupoint (the spot below the costal region, i.e., 2 cm superior to the
      posterior superior iliac spine and about 3 cm lateral to the spine) was punctured
      and stimulated for about 1 min by using a filiform needle, once daily for 30 days
      except the weekends. The rats' learning-memory ability was detected by Morris
      water maze tasks. The expression of gap junction-related proteins connexin 43 (CX
      43), CX 32 and CX 36 in the frontal cortex tissue was detected by
      immunohistochemistry. RESULTS: After modeling, the postnatal rats' eye-open time
      on day 14, 15 and 16 was significantly later (P < 0.05); and the swimming ability
      on postnatal day 13 and 15 was obviously lower in comparison with that of the
      control group (P < 0.05). After acupuncture treatment, the increased escape
      latency and the decreased swimming velocity of the autism rats were obviously
      suppressed in the GV 1 group, rather than in the non-acupoint group (P < 0.05).
      It suggests an improvement of learning-memory ability after acupuncture
      stimulation of GV 1. In comparison with the control group, the expression levels
      of cerebral CX 43, CX 32 and CX 36 proteins (mean grey values) were considerably
      down-regulated in the model group (P < 0.05). While compared to the model group,
      their expression levels were apparently up-regulated in the GV 1 group (P < 0.05)
      but not in the non-acupoint group. CONCLUSION: Acupuncture intervention of GV 1
      can improve the learning- memory ability in autism rats, which may be closely
      related to its effects in up-regulating expression levels of CX 43, CX 32 and CX
      36 in the frontal cortex.

PMID- 25069192
TI  - [Effects of needle pricking therapy of Zhuang minority medicine on expression of
      pulmonary T-bet, GATA-binding protein 3 genes and thymic stromal lymphopoietin
      protein in the lung of asthma mice].
AB  - OBJECTIVE: To observe the effect of needle pricking therapy on the expression of
      thymic stromal lymphopoietin (TSLP) protein, T-box expressed in T cells(T
      bet)mRNA and GATA-binding protein-3 (GATA 3) mRNA in the lung tissue of mice with
      asthma, so as to explore its mechanism underlying improvement of asthma. METHODS:
      Thirty female BALB/c mice were randomly divided into control, model and needle
      pricking groups (10 mice/group). The asthma model was established by i. p. of
      Ovalbumin (OVA) suspension fluid (containing Aluminium Hydroxide 400 microg and
      OVA 100 microg, 50 microg/L) and forced inhalation of atomized OVA. A sharp
      needle was held to prick "Dazhui" (GV 14),"Feishu" (BL 13), "Dingchuan" (EX-B
      1),"Fengmen" (BL 12),"Shenshu" (BL 23) and "Pishu" (BL 20) acupoint regions to
      let a little bit of white fibrous tissue out, then to insert into the acupoints
      to about 1 mm in depth, once a day for seven times. The lung tissue was taken for
      detecting the expression of T-bet mRNA and GATA-3 mRNA by RT-PCR and for
      determining the immunoactivity of TSLP by immunofluorescence method. In addition,
      HE staining was used to examine the pathologic changes of the lung tissue.
      RESULTS: Compared with the control group, the expression levels of GATA-3 mRNA
      and TSLP protein of the lung tissue in the model group were significantly
      increased (P < 0.01), whereas that of T-bet mRNA was remarkably decreased (P <
      0.05). Following needle prick stimulation treatment, the expression levels of
      GATA-3 mRNA and TSLP protein were markedly down-regulated (P < 0.01) and that of
      T-bet mRNA was obviously upregulated (P < 0.05). After the treatment,
      pathological changes including hyperemia of the pulmonary alveoli, epithelial
      thickening, narrowing of the lumina, and infiltration of many inflammatory cells
      around the tracheal blood vessels were improved. CONCLUSION: Needle pricking
      therapy can regulate the expression of pulmonary TSLP protein and GATA 3 and T
      bet genes in mice with asthma, which may contribute to its effect in improving
      pulmonary pathological changes of asthma mice.

PMID- 25069193
TI  - [Effect of electroacupuncture intervention on levels of SOD, GSH, GSH-Px, MDA,
      and apoptosis of dopaminergic neurons in substantia Nigra in rats with
      Parkinson's disease].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on superoxide (SOD),
      glutathione peroxidase (GSH-Px) activity, contents of glutathione (GSH) and
      malondiadehyde (MDA), and expression of tyrosine hydroxylase (TH) and apoptosis
      of Dopaminergic (DA) neurons in Substantia Nigra of rats with Parkinson's disease
      (PD). METHODS: Adult male Wistar rats were randomly divided into normal (10
      rats), model (11 rats), EA (11 rats) and medication (11 rats) groups. The PD
      model was established by i.h. of Rotenone (0.8 mg/kg) for 28 days. EA stimulation
      (2 Hz/80 Hz, 2 mA) was applied at "Baihui" (GV 20), "Sanyinjiao" (SP 6) and
      "Taichong" (LR 3) acupoints for 10 min, once per day for 14 times. For rats in
      the medication group, Madopar suspension fluid (1.67 mg/kg) was given by gavage
      for 14 days. Xanthine oxidase method and colorimetric ana- lysis method were used
      to examine the SOD, GSH-Px activity and contents of GSH and MDA in the Substantia
      Nigra tissue of the right brain, respectively. Immunohistochemical technique was
      used to detect the TH positive neurons and TUNEL method was used to examine the
      apoptosis of DA neurons of the Substantia Nigra in the left brain. RESULTS:
      Following the intervention, the decreased SOD and GSH-Px activity, GSH contents,
      and the increased MDA content of the Substantia Nigra in PD rats were obviously
      reversed by EA intervention (P < 0.05) but not by medication except MDA content
      (P > 0.05). In comparison with the model group, the decreased TH immunoactivity,
      and the increased numbers of apoptotic cells of DA neurons were apparently
      suppressed in both EA and medication groups (P < 0.05), but without significant
      differences between the EA and the medication groups (P > 0.05). In addition, HE
      stain showed that EA intervention could improve PD-induced impairment of
      Substantia Nigra neurons (mild swelling of neurons with large nucleus and
      deranged fibers). CONCLUSION: EA intervention can reduce pathological changes of
      Substantial Nigra in PD rats, which is probably associated with its effects in up
      regulating the SOD and GSH-Px activity, GSH contents, and down-regulating MDA
      level, and reducing the apoptosis of DA neurons of the Substantia Nigra,
      suggesting an anti-oxidative stress effect of EA therapy.

PMID- 25069194
TI  - [Effects of electroacupuncture stimulation of "Jiaji" (EX-B 2) on expression of
      matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 in
      intervertebral disc tissue in rabbits with lumbar intervertebral disc
      degeneration].
AB  - OBJECTIVE: To observe the effect of electroacupuncture(EA) stimulation of "Jiaji"
      (EX-B 2) on the expression of matrix metalloproteinase-13 (MMP-13) and tissue
      inhibitor of metalloproteinase-1 (TIMP-1) proteins in the lumbar disc in rabbits
      with lumbar intervertebral disc degeneration so as to explore its mechanism in
      relieving intervertebral disc degeneration. METHODS: A total of 36 New Zealand
      rabbits were randomly divided into normal, sham operation (sham), model, and EA
      groups, with 9 rabbits in each group. The lumbar intervertebral disc degeneration
      model was established by using a custom-made external loading device to axially
      compress the lumbar discs (L4, L5) for 28 days in reference to Kroeber and
      colleagues' methods. After modeling, EA stimulation (2 Hz/15 Hz, 1-2 mA) was
      applied to bilateral "Jiaji" (EX-B 2) areas for 20 min, once daily for 28 days.
      The expression levels of MMP-13 and TIMP-1 proteins of the lumbar intervertebral
      disc (L4-L5) tissues were assayed by Western blot and immunoflorescence methods,
      separately. RESULTS: Compared to the normal and sham groups, MMP-13 expression
      levels at the time-points of day 28 in the model group, on day 28 (pre-EA) in the
      EA group were significantly up-regulated (P < 0.01); and TIMP-1 expression levels
      on day 28 in both model and EA groups were significantly decreased (P < 0.01).
      Following EA treatment, the expression level of MMP-13 was notably lower in the
      EA group than in the model group, and that of TIMP-1 was remarkably higher in the
      EA group than in the model group (P < 0.01). No significant differences were
      found in the expression levels of MMP-13 and TIMP-1 from day 1 to day 56 in the
      same one group of both normal and sham groups, and between these two groups (P >
      0.05). CONCLUSION: Electroacupuncture at "Jiaji" (EX-B 2) can effectively
      suppress intervertebral disc degeneration induced up-regulation of MMP-13 protein
      and down-regulation of TIMP-1 protein in the disc tissue in rabbits, which may
      contribute to its effect in bettering lumbago in clinic.

PMID- 25069196
TI  - [Effects of electroacupuncture stimulation of "Daimai" (GB 26) on body weight,
      blood glucose and blood lipid levels in rats with metabolism syndrome].
AB  - OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA)
      stimulation of "Daimai" (GB 26) on metabolic syndrome in rats. METHODS: SD rats
      were randomly divided into blank control group (n = 9), model group (n = 9) and
      EA group (n = 9). The metabolic syndrome model was established by feeding the
      rats with high fat and sugar forage (containing 20% lard, 10% cane sugar, 10%
      defatted milk powder, 2% cholest, 3% yolk powder and 55% normal forage) for 12
      weeks. EA (2 Hz/100 Hz, 1-2 mA) was applied to bilateral "Daimai" (GB 26) for 20
      min, once daily for 4 weeks. Fasting blood glucose (FBG), serum triglyceride
      (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), lower
      density lipoprotein-cholesterol (LDL-C) contents were detected using chemical
      methods,fasting serum insulin (FINS) was determined by using radioimmunoassay.
      Homeostasis model assessment-index of resistance (HOMA-IR, insulin resistance
      index = FBG x FINS/22.5) was calculated. RESULTS: Compared to the blank control
      group, the body weight (from the 8th week on),abdominal circumference (from the
      4th week on), and FBG, FINS, TG, TC, LDL-C contents as well as HOMA-IR in the
      model group were significantly increased (P < 0.05, P < 0.01), while the HDL-C
      content was considerably lowered after modeling (P < 0.05). In comparison with
      the model group, the body weight on the 16th week, FBG, FINS, HOMA-IR, TG, TC and
      LDL-C levels were evidently down-regulated in the EA group (P < 0.05, P < 0.01).
      No significant differences were found between the model and EA groups in the
      abdominal circumference and HDL-C content (P > 0.05). CONCLUSION:
      Electroacupuncture stimulation of "Daimai" (GB 26) can reduce insulin resistance,
      regulate blood lipid, and lower blood glucose in metabolic syndrome rats.

PMID- 25069195
TI  - [Effects of electroacupuncture stimulation of "Sanyinjiao" (SP 6) on
      hypothalamus'-pituitary-ovary axis in perimenopausal rats].
AB  - OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Sanyinjiao"(SP
      6) on hypothalamus-pituitary-ovary (HPO) axis in perimenopausal rats so as to
      study its underlying mechanisms in improving dysfunction of HPO axis. METHODS:
      Eight female SD rats with an age of 3 months were used as the normal control
      group, other 16 perimenopausal SD rats with an age of 11-15 months were equally
      randomized into model group and EA group. The menopause model was confirmed by
      vaginal smear tests for successive 15 days. EA (2 Hz/100 Hz) was applied to
      bilateral "Sanyinjiao"(SP 6) for 20 min, once every other day for 30 days. After
      the treatment, the rats' hypothalamus, pituitary and left ovary tissues were
      collected for detecting the contents of gonadotropin releasing hormone (GnRH),
      follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2)
      by ELISA. RESULTS: Compared with the normal control group, the ovary E2 content
      of the model group was significantly decreased (P < 0.01), and the pituitary FSH
      and LH contents, and hypothalamic GnRH content were obviously increased in the
      model group (P < 0.01). Following EA intervention, the ovary E2 level was
      obviously elevated (P < 0.05), while pituitary FSH and LH and hypothalamic GnRH
      levels were significantly down-regulated in comparison with the model group (P <
      0.05). CONCLUSION: EA of "Sanyinjiao" (SP 6) can suppress menopause-induced down
      regulation of ovary E2 and increase of pituitary FSH and LH and hypothalamic GnRH
      levels in perimenopausal rats, suggesting a favorable regulation of EA on HPO
      axis dysfunction.

PMID- 25069197
TI  - [Effects of electroacupuncture stimulation at "Guanyuan" (CV 4) on serum insulin
      like growth factor-1 content and bone biomechanics in ovariectomy-induced
      osteoporosis rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on serum insulin-like
      growth factor-1 (IGF-1) content and bone biomechanics in osteoporosis rats so as
      to explore its mechanism underlying improvement of postmenopausal osteoporosis
      (PMOP). METHODS: Forty female SD rats (4.5 months old) were randomly divided into
      sham-operation (sham), model, medication and EA groups (10 rats/group). The rat's
      bilateral ovaries were removed to establish the PMOP model. For rats in the sham
      group, similar procedures were conducted except removing comparable weight of fat
      tissues around the ovaries. For rats in the EA group, "Guanyuan" (CV 4) was
      punctured with filiform needles and stimulated electrically (1 mA, 2 Hz) for 20
      min, once a day for 30 days. For rats in the medication group, pentanoic acid
      estradiol (50 microg/500 g) was administrated by gavage. The serum IGF-1 content
      was examined by ELISA and the bone biomechanics measured by three-point bending
      tests, respectively. RESULTS: Compared with the sham group, the serum IGF-1
      level, femoral maximum load and fracture load were significantly reduced in the
      model group (P < 0.05, P < 0.01). In comparison with the model group, these
      indexes were significantly increased in rats of the EA and medication groups (P <
      0.05, P < 0.01), but without significant difference between the EA and medication
      groups (P > 0.05). CONCLUSION: EA produces benefits on postmenopausal
      osteoporosis through increasing the serum IGF-1 contents and bone strength.

PMID- 25069198
TI  - [Effects of moxibustion at "Ganshu" (BL 18) on serum alpha-fatoprotein and liver
      livin levels in rats with precancerous lesion of primary hepatocellular
      carcinoma].
AB  - OBJECTIVE: To observe the effect of moxibustion at "Ganshu" (BL18) on levels of
      Livin (a novel member of the inhibitors of apoptosis family and plays crucial
      roles in apoptosis, cell proliferation, and cell cycle control) in the liver
      tissue in rats with precancerous lesion of primary hepatocellular carcinoma
      (HCC), so as to explore its mechanism underlying improvement of HCC. METHODS:
      Sixty male Wistar rats were randomly divided into control group (n = 10), model
      group (n = 20), moxibustion-20 d group (n = 15) and moxibustion-40 d group (n =
      15). HCC model was established by intraperitoneal injection of diethylnitrosamine
      (DEN, 50 mg/kg), once every 3 days for 12 weeks. Moxibustion was applied to
      bilateral "Ganshu" (BL 18), once every other day for 10 times (moxibustion-20 d
      group) and 20 times (moxibustion-40 d group), respectively. Serum alpha
      fetoprotein (AFP) content was detected with ELISA and Livin immunoactivity of the
      liver tissue detected using immunohistochemistry. RESULTS: After modeling, serum
      AFP content and liver Livin immunoactivity of the model group were significantly
      increased in comparison with the control group (P < 0.01). After moxibustion
      treatment, serum AFP content in the moxibustion-20 d group and liver Livin
      immunoactivity in both moxibustion-20 d and moxibustion-40 d groups were
      remarkably down-regulated in comparison with the model group (P < 0.05). No
      significant differences were found between the moxibustion-40 d group and the
      model group in serum AFP content (P > 0.05). CONCLUSION: Moxibustion can down
      regulate liver Livin protein expression, which probably has a role in promoting
      hepatocellular apoptosis to inhibit precancerous lesion and to postpone
      hepatocarcinogenesis.

PMID- 25069199
TI  - [Effect of dexmedetomidine and midazolam on respiration and circulation functions
      in patients undergoing open heart surgery under acupuncture-assisted general
      anesthesia].
AB  - OBJECTIVE: To evaluate the effect of Dexmedetomidine and Midazolam on respiratory
      and circulation in patients experiencing open heart surgery under acupuncture
      assisted general anesthesia. METHODS: Sixty patients undergoing open heart
      surgery (cardiac valve replacement surgery and aortic valve replacement surgery)
      were randomly and equally divided into Dexmedetomidine (D) and Midazolam (M)
      groups. Electroacupuncture (EA) was applied to bilateral Yunmen (LU 2), Zhongfu
      (LU1), Lieque (LU7) and Neiguan (PC6). For patients of group D, Dexmedetomidine
      (i.v., loading dose: 1 microg/kg, and succedent dose: 0.2-1 microg x kg(-1) x h(
      1)) was given. For patients of group M, Midazolam (i.v., loading dose: 0.05
      mg/kg, succedent dose: 0.01-0.03 mg x kg(-1) x h(-1)) was given. Arterial oxygen
      pressure (PaO2), arterial carbondioxide tension (PaCO2), O2 saturation (SPO2),
      mean arterial pressure (MAP), heart rate (HR), anesthetic effect, time of
      spontaneous breathing recovery, and time of resuscitation were recorded before
      operation (T0), immediately after skin incision (T1), immediately after
      sternotomy (T2), before suspension of cardiopulmonary bypass (CPB, T3),
      immediately after cardiac re-beating (T4), immediately after CPB cessation (T5),
      and at the end of surgery (T6). RESULTS: Before operation, no significant
      differences were found between the group D and M in the levels of PaO2, PaCO2 and
      SPO2 (P > 0.05). The PaO2 and SPO2 levels after skin incision, sternotomy, before
      suspension of CPB and at the end of surgery were significantly lower in group M
      than in group D (P < 0.05), while the le- vels of PaCO2 after skin incision,
      sternotomy, before suspension of CPB and at the end of surgery, and HR after skin
      incision, sternotomy, before suspension of CPB, after heart re-beating,after CPB
      cessation and at the end of surgery in group M were considerably higher than
      those in group D (P < 0.05). In addition, the time of spontaneous breathing
      recovery of group M was significantly later than that of group D (P < 0.05). No
      significant differences were found between the two groups in MAP levels at the 6
      time-points during surgery, in the PaO2, PaCO2 and SPO2 levels at the time-points
      of post-cardiac re-beating, and after CPB cessation (P > 0.05). It suggested that
      the respiration and circulation states in group D were more smoothly than those
      in group M. There was no significant difference between the two groups in the
      time of resuscitation (P > 0.05). CONCLUSION: Dexmedetomidine is superior to
      Midazolam in analgesia, and improving respiration and circulation functions for
      open heart surgery patients under acupuncture-assisted general anesthesia.

PMID- 25069201
TI  - [Effect of warm acupuncture stimulation of Waiguan (TE 5) on post-stroke shoulder
      hand syndrome].
AB  - OBJECTIVE: To evaluate the therapeutic effect of warm acupuncture (moxa-heated
      acupuncture) needle stimulation of Waiguan (TE 5) acupoint in the treatment of
      shoulder-hand syndrome (phase I) in patients with stroke. METHODS: Sixty stroke
      patients with shoulder-hand syndrome (phase I ) were equally randomized into
      control group and warm acupuncture group. Patients of the warm acupuncture group
      were treated by warm acupuncture stimulation of the affected TE 5 in combination
      with routine acupuncture stimulation of Jianyu (LI 15), Jianjing (GB 21), Quchi
      (LI 11), Wangu (SI 4), Yangchi (TE 4) and Hegu (LI 4), and rehabilitation
      training (passive and active upper-limb motion exercise for 30 min, once daily),
      and patients of the control group treated with routine acupuncture stimulation of
      the same acupoints mentioned above, and rehabilitation training. The treatment
      was conducted once daily, 5 times per week for two weeks. The patients' clinical
      conditions were evaluated by using Visual Analogue Scale (VAS, 0-10 points,
      shoulder pain degree), edema severity score (0 point:normal, 2 points: mild, 4
      points: moderate, and 6 points: severe) and simplified Fugl-Meyer motor
      assessment scale (0, 1 and 2 points, upper-limb motor function) before and after
      the treatment. RESULTS: After the treatment, the scores of VAS and edema severity
      of the two groups were significantly decreased in comparison with pre-treatment
      in the same one group (P < 0.01), and the Fugl-Meyer motor scores were
      considerably increased (P < 0.01), suggesting an improvement of the shoulder-hand
      syndrome after two weeks' treatment. Of the two 30 patients in the control group
      and warm acupuncture group, 0 and 2 (6.7%) were cured, 7 (23.3%) and 25 (83.3%)
      experienced marked improvement, 17 (56.7%) and 2 (6.7%) were effective, 6 (20.
      0%) and 1 (3.3%) invalid, with the effective rates being 80.0% and 96.7%,
      respectively. The effect of warm acupuncture group was superior to that of the
      control group (P < 0.05). CONCLUSION: Warm acupuncture combined with routine
      acupuncture and rehabilitation training is effective in improving shoulder pain,
      hand edema and limb motor function in stroke patients with shoulder-hand syndrome
      at phase I.

PMID- 25069200
TI  - [Influence of different skin reactions of acupoint-application on clinical
      outcomes in the prevention and treatment of bronchial asthma].
AB  - OBJECTIVE: To observe the influence of different skin reactions of acupoint
      application in summer on outcomes of prevention and treatment of bronchial
      asthma. METHODS: All of the bronchial asthma patients were treated with acupoint
      application therapy in the dog-days of summer, once every ten days, 3 times
      altogether. After the treatment, according to scores of the skin reactions
      including flush, itching, pain, vesicles, etc. induced by acupoint-application of
      prepared Chinese medical herb paste, 164 cases were divided into four groups: no
      reaction (n = 43), mild reaction (n = 42), moderate reaction (n = 39) and severe
      reaction (n = 40). One-year's follow-up was conducted after the treatment for
      assessing the asthma patients' cough-asthma score, wheezing rale score, and for
      recording the attack times. RESULTS: After the treatment, the cough-asthma
      scores, wheezing rale scores, and asthmatic attack times were obviously decreased
      in all the 4 groups compared to pre-treatment (P < 0.05, P < 0.01). Comparison
      among the 4 groups showed that the levels of the 3 indexes were significantly
      higher in the no reaction group and mild reaction group than in the moderate and
      severe reaction groups after the treatment (P < 0.05, P < 0.01), suggesting a
      better therapeutic effect in patients undergoing moderate and severe skin
      reactions. There were no significant differences between the no reaction and mild
      reaction groups, and between the moderate reaction and severe reaction groups in
      the levels of the 3 indexes (P > 0. 05). The total effective rates of the no
      reaction, mild reaction, moderate reaction and severe reaction groups were
      58.14%, 88.10%, 94.87% and 97.50%, respectively. The mild, moderate and severe
      reaction groups were better than the no reaction group in the therapeutic effect
      (P < 0.01). The mild reaction group was poorer than the moderate and severe
      reaction groups in clinical efficacy (P < 0.05). There was no marked difference
      between the moderate and severe reaction groups in clinical outcomes (P > 0.05).
      CONCLUSION: Acupoint-application in the dog-days can effectively improve the
      asthma patients' symptoms, and the therapeutic effect of patients experiencing
      moderate and severe skin reactions was better.

PMID- 25069202
TI  - [A meta-analysis on pricking blood therapy for migraine].
AB  - OBJECTIVE: To evaluate the therapeutic effect of pricking blood therapy for
      migraine. METHODS: We searched all the original papers about pricking blood
      therapy for migraine in common databases as the Chinese National Knowledge
      Infrastructure Database (CNKI), Chinese Biomedical Library (CBM), Ovid, Science
      Direct, Socolar, and Sci Finder (1949 -2012), Wanfang Data (1998-2012) and
      Foreign Medical Journal Service (FMJS, 1990-2012). The original articles were
      searched in accordance with a pre-defined standards (simple pricking blood
      treatment, or the pricking blood therapy was the principal approach), while those
      about other diseases (such as cerebrovascular disease, cervical spondylosis,
      etc.) evoked migraine, pricking blood used as a complementary therapy, case
      report, specialists' experience summary, reviews, surveys, news articles, animal
      studies were excluded. Then, a Meta-analysis was made by software Review Manager
      5.1. RESULTS: A total of 11 clinical trial papers involving 826 cases of migraine
      were included in the present paper. Three of them were high-quality researches,
      and the other eight were low quality researches. Results of Meta-analysis
      indicated that the therapeutic effect of the pricking blood therapy was
      significantly superior to that of non-bleeding therapies in relieving migraine
      [OR = 6.23, 95% CI: (4.03, 9.63), Z = 8.24, P < 0.00 001]. However, the poor
      symmetry of funnel plot suggested a risk of bias. CONCLUSION: The pricking blood
      therapy is effective for relieving migraine, but larger sample clinical trials,
      particularly randomized controlled trials are definitely needed for confirming
      the conclusion.

PMID- 25069203
TI  - [A meta-analysis on acupuncture treatment of polycystic ovary syndrome].
AB  - OBJECTIVE: To evaluate the effect and safety of acupuncture treatment of
      polycystic ovary syndrome (PCOS) by using systematic review in view of evidence
      based medicine (EBM). METHODS: Original articles about acupuncture treatment of
      PCOS published from the database-established year to November of 2013 were
      searched from the Chinese National Knowledge Infrastructure Database (CNKI),
      Chongqing VIP Chinese Science and Technology Periodical Database (VIP), Chinese
      Biomedical Library (CBM), Wanfang Data, PubMed, and the Cochrane Library and the
      associated references-indicated papers by using keywords of polycystic ovary
      syndrome, randomization, acupoint, acupuncture, acupuncture plus moxibustion,
      acupuncture plus acupoint-embedment of catgut, and acupuncture plus otopoint
      application. Those articles about treatment of PCOS with simple abdominal
      acupuncture, simple acupoint-embedment of catgut, simple otopoint-pellet
      pressure, and simple moxibustion treatment, and simple abstracts were excluded.
      If the articles re-published in both Chinese and English and in academic
      conferences and journals, one of them with higher quality was included. Two
      independent reviewers extracted data from located articles in a pre-defined
      structured way, and the Meta-analysis was conducted using software RevMan 5.2,
      otherwise using the qualitative analysis. RESULTS: A total of 31 articles (28 in
      Chinese, 3 in English) containing 2,321 cases of PCOS patients met the included
      criteria. Meta-analysis showed that the clinical efficacy of simple acupuncture
      was the same as that of western medicine, and the efficacy of acupuncture
      combined with Chinese herbal medicine interventions was obviously higher than
      that of western medicine (P < 0.05). In addition, simple acupuncture intervention
      and acupuncture combined with Chinese herbal medicines or with moxibustion
      treatment have advantages in reducing serum luteinizing hormone/follicle
      stimulating hormone (LH/FSH), insulin resistance (IR), testosterone (T), and body
      mass index (BMI). However, the quality of the collected articles is generally
      lower due to unclear bias, no sample quantity estimation, incorrect randomization
      methods, no follow-up survey, etc. CONCLUSION: Acupuncture therapy may be
      effective for PCOS, but needs to be confirmed further by larger sample randomized
      controlled trials.

PMID- 25069204
TI  - [Bibliometrics analysis on researches of illness spectrum for acu-moxibustion
      therapy and prospect].
AB  - The research on indications of acu-moxibustion is very important for effectively
      guiding clinical practice. In the present paper, the authors retrieved domestic
      literature about researches on the disease-spectrum or indications of acu
      moxibustion therapy in recent 10 years, and made a bibliometrics analysis
      according to the described research methods, publishing year, quantity and their
      proportionate relationship. A total of 18 qualified original papers involving 414
      illnesses or clinical conditions were included in the present paper. Among the
      414 kinds of clinical conditions or illnesses, 72 were considered to be suitable
      candidates for acu-moxibustion therapy, including functional dyspepsia, herpes
      zoster, irritable bowel syndrome, gastrointestinal dysfunction, scapulohumeral
      periarthritis, cervical syndrome, dyssomnia, acne (cyst type), chronic urticaria,
      regional neurodermatitis, pain, itching, etc. which belong to illness-spectrum
      grade-I. Generally, the acu-moxibustion therapy is, in clinical effects,
      relatively poorer for structural diseases which are attributed to grade-II or
      grade-III type. Nevertheless, the diversity of clinical indications of acu
      moxibustion has been confirmed nowadays. Current studies on illness-spectrum are
      of certain uniformity and comprehensiveness, but need further extending and
      perfecting, and need more standardized methods corresponding to principles of the
      evidence-based medicine.

PMID- 25069205
TI  - [A feasibility analysis on individualized acupuncture treatment of irritable
      bowel syndrome under help of genetic polymorphism technique].
AB  - Along with the application of genetic polymorphism techniques to individualized
      treatment of clinical disorders, the screening of polymorphisms markers of
      serotonin (5-HT) transporter (SERT) is a hot-spot of researches on irritable
      bowel syndrome (IBS). In the present paper, the authors introduce 1) optimized
      schemes of diagnosis and treatment of IBS on the basis of syndrome
      differentiation for acupuncture in combination with Chinese herbal medicines, and
      application of 5-HT transporter polymorphism, 2) application of genetic
      polymorphism to researches on IBS, and 3) feasibility of genetic polymorphism
      techniques for guiding individualized treatment of IBS. Up to now, serotonin
      transporter length polymorphic region (5-HTTLPR), serotonin transporter intron 2
      variable number of tandem repeat (Stin 2 VNTR) and single nucleotide polymorphism
      rs 25531 in the long allele of the 5-HTTLPR have been identified. On the basis of
      the treatment of IBS, we need establishing a set of guide lines for the
      individualized acupuncture treatment. The genotyping methods for genetic
      polymorphism should be widely used in this research field. 5-HT TLPR/ Stin 2
      VNTR/rs 25531 polymorphisms would have a bright future in the field of IBS
      research and treatment.

PMID- 25069207
TI  - 50th anniversary of Declaration of Helsinki.

PMID- 25069206
TI  - [Development of studies on influence of patients' expectations on therapeutic
      effects of acupuncture and moxibustion interventions].
AB  - The patient's expectations (placebo effects) refer to the anticipation or the
      belief about what is to be encountered in a consultation in the healthcare
      system. Currently, it is a hot-spot for researching its influence on clinical
      outcomes of acupuncture and moxibustion interventions. How to evaluate the
      magnitude of patients'expectations is a problem needing to be solved urgently at
      the moment. The authors of the present paper make a summary about researches on
      the mechanism of expectations. For example, placebo analgesia was related to
      decreased brain activity in pain-sensitive brain regions (thalamus, insula, and
      anterior cingulate cortex), and to the increased activity of the prefrontal
      cortex showed by fMRI, and to the release of endogenous opioids. In addition, the
      authors also introduce some methods (psychological scales) for assessing
      expectations and related influencing factors (physicians or acupuncturists, and
      medical environment) for future research in this area. In the coming clinical
      trials on acupuncture or moxibustion treatment of clinical disorders, we should
      further better our experimental design, and try our best to exclude placebo
      effect-associated or expectation-induced bias of clinical outcomes for confirming
      the therapeutic effects in the treatment of different clinical problems.

PMID- 25069208
TI  - A comparative study on first stage versus second stage caesarean section on
      maternal and perinatal outcome.
AB  - BACKGROUND: Caesarean delivery (C/D) can be done in the first or second stage of
      labor. One fourth of the primary C/D are reported to be performed in the second
      stage of the labor but are more complicated compared to the ones performed in the
      first stage. OBJECTIVE: To compare maternal and perinatal outcomes of caesarean
      delivery (C/D) performed in the second stage of labor compared with the first
      stage in the Ethiopian setting. METHODS: An institution based comparative cross
      sectional study was conducted in three teaching hospitals in Addis Ababa,
      Ethiopia. A sample size calculation for double proportion was used, and, for
      every second stage C/D, the next three consecutive first stage C/D cases were
      taken as controls till the desired sample size was achieved. mean and standard
      deviation for continuous and proportion for categorical variables were used for
      descriptive statistics. T-test for difference in independent mean and chi square
      test to compare proportions was utilized. Odds ratio with 95% CI was used to
      measure the strength of association of selected variables. RESULT: A total of
      3238 deliveries were attended in the three teaching hospitals during the study
      period making the (C/D rate of 30.1%. Three hundred eighty-eight emergency
      caesarean delivery cases were enrolled using the aforementioned technique with
      the proportion of 97 (10.9%) second stage and 291 (89.1%) first stage C/D. The
      most common indications in the first stage were non-reassuring fetal heart rate
      pattern (NRFHRP) accounting for 110 (37.8%) followed by arrest or protraction
      disorder of 68 (23.4%), whereas the commonest indication for the second stage C/D
      was cephalopelvic disproportion 46 (48.5%). Significant difference observed in
      the mean blood loss between the second stage and first stage C/D, 552 ml vs. 410
      ml, (OR 30.13, 95% CI 16.25-55.85). Similarly, the women in the second stage C/D
      had longer mean hospital stay and mean longer operation time than first stage
      C/D, 5.34 vs. 6.96 days, (OR 1.72, 95% CI 1.05-2.85), and 31.12 min vs. 37.5, (OR
      2.33, 95% CI 1.33-4.07), respectively. Five caesarean hysterectomies were done
      for postpartum haemorrhage and four cases of extension of incision site were
      encountered following second stage C/D compared to none in the first stage C/D.
      CONCLUSION: Though no maternal death or significant perinatal complications were
      encountered, women with second stage C/D had significant maternal morbidities
      than first stage cesarean delivery. Therefore, utmost effort should be made to
      avoid the procrastination of the decision for C/D to the second stage, but if
      such compelling situations are encountered, precautions, like involvement of the
      most senior person and vigilance to minimize the expected complications is
      warranted.

PMID- 25069209
TI  - Spectrum of cardiovascular diseases among Ethiopian patients at Tikur Anbessa
      Specialized University Teaching Hospital, Addis Ababa.
AB  - BACKGROUND: Cardiovascular disorders vary throughout the world in type and
      distribution especially between the developed and the developing countries. Data
      on spectrum of cardiovascular diseases in Ethiopia is scarce. OBJECTIVE: To
      assess the spectrum of cardiovascular disorders at Tikur Anbessa Specialized
      Tertiary Referral Hospital. METHODS: A record review of patient registers from
      January 2001 to December 2012 was done for 3282 Ethiopian patients with confirmed
      cardiovascular disorders at adult Cardiology clinic and Neurology clinic of Tikur
      Anbessa Specialized hospital. Spectrum of valvular heart disease, heart failure,
      hypertension, ischemic heart disease, congenital heart disease, arrhythmias,
      cardiomyopathies, cerebrovascular diseases, and peripheral vascular diseases,
      defined by Physician International Classification of Diseases, Version 9, codes,
      were directly standardized to the population. Descriptive statitistics was
      applied to present results. RESULTS: The study population contained more women (n
      = 1937 [59.0%]) than men. The mean age of the patients was 31.6 +/- 16.6 years.
      Women were younger than men (mean 29.6 [SD 15.1] years vs 34.52 [18.3] years).
      Valvular Heart Disease was the most common primary diagnosis in 2036 (62.0%) with
      significantly higher proportion in the 3rd decade of life. About 300 (9.1%) of
      the patients were diagnosed with heart failure. Other major diagnoses included
      hypertension 482 (14.7%), cerebrovascular diseases or stroke 377 (11.5%),
      congenital heart disease 279 (8.5%) and ischemic heart disease 224 (7.4%). Fifty
      seven (26.5%) patients with ischemic heart disease had diabetes mellitus.
      CONCLUSION: While valvular heart disease is the commonest cardiovascular disorder
      in Ethiopian patients at the largest public hospital of the country, ischemic
      heart disease has dramatically increased over the years. It is high-time that
      effective population-based, health promotive strategies for primary prevention as
      well as secondary measures for the established cardiovascular disorders and risk
      factors are in place.

PMID- 25069210
TI  - Patterns of enlarged cervical lymph nodes among HIV positive and negative
      patients in southwestern Ethiopia: a cytopathlogic analysis.
AB  - OBJECTIVE: The human immunodeficiency virus (HIV) epidemic facilitated the
      resurgence of extrapulmonary tuberculosis (TB) and other opportunistic diseases.
      This study assessed the sociodemographic and cytopathologic patterns of enlarged
      cervical lymph nodes among HIV positive and negative patients. MATERIALS AND
      METHODS: This prospective cross sectional study was conducted in Agaro Health
      centre, Agaro town, Oromia regional state, south western Ethiopia, for a period
      between April 2008 and September 2008. The instruments of the study were a
      structured questionnaire for data collection, fine needle aspirate cytology
      (FNAC) technique for the lymph nodes aspirates and blood drawn for HIV testing.
      The aspirates were also cultured by using Lowenstein-Jensen medium (LJ) medium.
      Finally, all data was cleaned, entered and analyzed by using SPSS version 13.00
      statistical software and P-Value was taken significant when less than 0.05.
      RESULTS: A total of 82 patients were enrolled into this study. Nineteen (23.2%)
      patients were HIV positive. Tuberculous adenitis was the most frequent diagnosis
      47/82 (57.3%). HIV positivity in patients with enlarged cervical adenopathy was
      19/82 (23.2%) however, HIV and TB adenitis co-infection was 12/47 (25.5%) in the
      studied patients (P-Value = 0.57). TB was diagnosed cytologically in 5/11
      ulcerated nodes, 11/28 purulent aspirates and 7/15 aspirates showing caseous
      necrosis without cellular reactions. CONCLUSIONS: About one-fourth (25.5%) of
      tuberculous lymph adenitis patients were co-infected with HIV. Pussy aspirates
      macroscopically and caseous necroses without cellularity microscopically were
      more common among HIV positive patients in this study. Thus, caseous necrosis
      with acellular reactions with or without pussy aspirates and nodal ulceration
      could hint immunodeficient status in co-infected individuals but this speculation
      need to be verified in a larger scale prospective study.

PMID- 25069211
TI  - Contraceptive method choice and use by married women of reproductive age in two
      Districts of East Harerge.
AB  - BACKGROUND: Contraceptive method mix and choice is not uniform across all
      countries. Literatures have shown that a significant variation exists in
      contraceptive method mix among regions and countries. In Africa most mothers rely
      on short-term contraceptives such as pills and injectables or traditional methods
      while in Asia and Latin America permanent methods mainly male and female
      sterilizations are commonly used. Though long-term methods of contraception are
      recommended for its effectiveness and efficiencies in countries like Ethiopia
      where high fertility rate is a concern, its choice and utilization remains low.
      OBJECTIVE: The main objective of the study was to assess factors influencing
      contraceptive method choice and use among married women of reproductive age in
      rural Districts of East Harerge Zone of Oromia Region. METHODS: A community-based
      cross-sectional study using both quantitative and qualitative methods was
      conducted among 473 married women of reproductive age in two rural districts of
      East Harerge Zone. A systematic random sampling method was used to select the
      study participants from the list of all married women who have been using
      contraceptives in the project sites. Data was collected using structured and
      pretested questionnaires. Data entry and analysis was done using EPI Info version
      6.04d and SPSS for Windows version 15, respectively. Frequencies and proportions
      were used for description while odds ratio with 95% CI was used to determine the
      strength and significance of association between independent and outcome
      variables. Multiple logistic regression analysis was used to control confounding
      variables. RESULTS: A total of 473 currently married women who were using modern
      contraceptives were interviewed for the survey. About 6 in ten (58.8%) were in
      the age range of 25-34 years with the mean (+/- SD) age of 29.5 (+/- 5.7) years.
      About three-fourth (74%) were short-term contraceptive method users while only
      26% were long-term contraceptive method users. Duration of family planning use,
      reasons for contraceptive use and provider's choice of the method were positively
      associated with long-term contraceptive use by married women of reproductive age
      in the study area. Qualitative finding showed that religious and cultural
      perceptions about contraceptives and values the society, particularly men, gives
      to large family size has negatively influenced contraceptive use. CONCLUSIONS:
      Long-term contraceptive method use is influenced by duration and reason for use
      of the methods and provider 's choice in the study area. Misconceptions about
      fertility regulations and the value the society gives to large family size do
      also affect contraceptive use. Beside availing contraceptives of choice,
      reproductive health/family planning awareness creation targeting religious
      leaders as well as interventions aimed at respecting women's right of accessing
      family planning method of their choice has to be strengthened in the study area.

PMID- 25069212
TI  - Critical appraisal of an article published in the Ethiopian Medical Journal.
AB  - Research involves gathering data, then collating and analyzing it to produce
      meaningful information. However, not all research is good quality and many
      studies are biased and their results untrue. Critical appraisal is the process of
      carefully and systematically examining research to judge its trustworthiness, and
      its value and relevance in a particular context. This paper attempted to point
      out the weak and strong points of the study, taking into account sources of bias
      that were introduced in the article "Visual acuity and road traffic accident
      (RTA) in Jimma town" published in the Ethiopian Medical Journal.

PMID- 25069213
TI  - Thalassemia syndrome.
AB  - A 16 years old female patient diagnosed to have thalassemia syndrome in Black
      lion Hospital based on clinical presentation, complete blood count, peripheral
      morphology and bone marrow findings.

PMID- 25069214
TI  - Epidural and para spinal thoracic hydatidosis presenting with progressive
      paraparesis and paraplegia: a case report.
AB  - We report a 16 year old male patient from rural Ethiopia with pathologically and
      intraoperatively proven thoracic para spinal and epidural hydatidosis, a very
      rare involvement, who presented with progresive both lower limb weakness, loss of
      pain, touch and properioception and double incontinence of two weeks prior to
      hospital admission. The pathological, radiological (MRI and plain x-ray) and the
      intra operative findings are briefly discussed with literature review.

PMID- 25069215
TI  - [The practical application of marker -2proPSA and health index of prostate phi in
      diagnostics of prostate cancer].
AB  - The article demonstrates that prostate-specific antigen (PSA) has some
      limitations in detection of cancer of prostate. It was demonstrated that isoform
      of free PSA - 2proPSA has higher specificity in comparison with total PSA (tPSA)
      and percentage tPSA and free PSA (%free PSA) in detection of cancer of prostate.
      The application of Prostate Health Index including such indicators as -2PSA, free
      PSA and tPSA makes it possible to increase degree of detection of cancer of
      prostate, to increase specificity and to decrease number of optional biopsies.
      Besides, correlation was established between value of Prostate Health Index and
      degree of aggressiveness of forms of cancer of prostate.

PMID- 25069216
TI  - [The association of leptin with dislipidemia in group of ethnic Kirghiz].
AB  - The article deals with results of evaluation of relationship between leptin and
      lipid indicators in group of ethnic Kirghiz. The sampling included 322 ethnic
      Kirghiz (145 males and 177 females) aged from 30 to 75 years. To all patients was
      applied general clinical examination, anthropometric examination (height, body
      mass, waist circumference, thighs circumference). The body mass index was
      calculated. The level of glucose (on an empty stomach), lipids spectrum and
      leptin of blood serum were measured. The average age of patients consisted 57.7
      +/- 9.6 years and average level of leptin was 7.8 ng/ml. The patients were
      allocated to three groups depending of tertile of leptin (< 3; 3.0-5.51; > or =
      5.52 ng/ml in males; 9.6; 9.6-16.6; > or = 16.7 ng/ml in females). In patients
      from upper tertile as compared with patients from lower tertiles are noted high
      values of triglycerides (p < 0.001), total cholesterol (p < 0.O01), in males and
      triglycerides (p = 0.02) in females. Leptin correlated with body mass index (in
      males: r = 0.68, p < 0.01; in females: r = 0.74, p < 0.001), concentration of
      triglycerides (in males: r = 0.301, p < 0.001; in females: r = 0.194, p < 0.001).
      Leptin correlated with total cholesterol in males (r = 0.214, p < 0.05) and with
      cholesterol of lipoproteins of high density in females (r = 0.156, p < 0.05). The
      level of leptin in group of ethnic Kirghiz is associated with dislipidemia,
      obesity, including abdominal obesity.

PMID- 25069217
TI  - [The diagnostic possibilities of saliva].
AB  - Saliva is a clinically informative biological fluid which contains multitude of
      bio-markers. This characteristic makes it possible to carry out numerous analyzes
      for developing mode to test patient in situ, express-tests included. The
      diagnostic by saliva is a new area of more simple application both markers and
      analyzers that can be useful in diagnostic of diseases of oral cavity,
      oncological diseases included. The using of saliva expands perspectives for
      making clinical diagnosis and establishment of dynamics and monitoring of
      disease.

PMID- 25069218
TI  - [The markers of lipid transport system of blood and annual prognosis of cardiac
      infarction].
AB  - The sampling included 133 patients with diagnosis of cardiac infarction with peak
      of segment ST. After a year after old cardiac infarction, in 38 patients were
      established such unfavorable outcomes of disease as progressive stenocardia,
      decompensation of cardiac failure, repeated cardiac infarction and lethal
      outcome. It is established that among all indicators of lipid profile detected at
      hospital period of cardiac infarction only three indicators are prognostically
      significant in groups of patients with different outcomes--levels of free fatty
      acids, oxidized modified lipoproteins of low density and antibodies to them.
      During hospital period, augmentation of concentration of free fatty acids,
      oxidized modified lipoproteins of low density and antibodies to them increases
      risk of development of distant complications of cardiac infarction. The
      mathematical model is proposed comprising as predictors free fatty acids and
      antibodies to oxidized modified lipoproteins of low density. This model makes it
      possible on the basis of biochemical data obtained during hospital period, to
      calculate individual cumulative risk and to develop long-term prognosis of
      probable outcome of cardiac infarction.

PMID- 25069219
TI  - [The positional isomers of triglycerides in oils, fats and apoB-100 lipoproteins:
      palmitic and oleic modes of metabolism of fatty acids-substrates for energy
      acquiring].
AB  - Even total resemblance of content of fatty acids in triglycerides has both no
      standing for their functional unity nor even identity of their physical chemical
      characteristics. The etherification of fatty acids in various positions of three
      atomic glycerin separates triglycerides on palmitic and oleic substrates for
      energy acquiring by cells. The kinetic parameters of biochemical reactions under
      palmitic mode of metabolism of fatty acids are always low. The myocytes in
      biological reaction of exotrophy experience deficiency of exogenous fatty acids
      which in vivo is to permanently supply through activation of biological reaction
      of endotrophy--enhancement of lipolysis in adipocytes. The biological role of
      insulin is to prevent formation in vivo of palmitic mode of metabolism of
      saturated and monoenic fatty acids. Under this condition, the necessity to
      activate lipolysis and to increase in blood plasma concentration of unesteritied
      fatty acids forms syndrome of resistance to insulin. The surplus of palmitic
      fatty acid in food and deficiency of insulin show in vivo unidirectional a
      physiologic action. The formation of palmitic mode of metabolism of energy
      substrates--portion of pathogenesis of atherosclerosis, metabolic syndrome,
      obesity, non-alcoholic fatty infiltration of liver and partiallly essential
      arterial hypertension.

PMID- 25069220
TI  - [The conformation of apoB-100 in phylogenetically and functionally different
      lipoproteins of low and very low density: algorithm of formation of phenotypes of
      hyper lipoproteinimia (a lecture)].
AB  - The cells' malabsorption of three classes of lipoproteins--chylomicrons and
      lipoproteins of low and very low density,--form under electrophoresis six
      phenotypes of hyperlipoproteinemia. In phylogenesis, cells absorb lipoproteins in
      a consecutive way by apoE/B-48, apoB-100 and apoE/B-100 receptor endocytosis. The
      domain-ligand in lipoproteins of very low density is forming when apoB-100 takes
      active conformation "deformed bilayer apoprotein-lipid" in association with
      domain apoE apoE/B-100 ligand is formed. Another active conformation apoB-100 in
      domain is globule with lipids in "pocket" forming apoB-100 ligand In blood 9
      subclasses are formed: pre-ligand and post-ligand chylomicrons, lipoproteins with
      low density and lipoproteins with very low density. The ligand lipoproteins bind
      receptors of membrane and absorb cells. Both pre-chylomicrons, pre-lipoproteins
      with low density, pre-lipoproteins with very low density and post-chylomicrons,
      post-lipoproteins with low density, post-lipoproteins with very low density
      remain in blood. The sub-classes of lipoproteins form at electrophoregram 6
      phenotypes of hyperlipoproteinemia: phenotype I-pre-chylomicrons + pre
      lipoproteins with very low density; phenotype IIa--post-lipoproteins with low
      density; phenotype IIb--pre-lipoproteins with very low density; phenotype III-
      post-chylomicrons + pre-lipoproteins with very low density; phenotype IV--pre
      lipoproteins with very low density; phenotype V--pre-chylomicrons + post
      chylomicrons + pre-lipoproteins with very low density + post-lipoproteins with
      very low density. The formation under electrophoresis of primary phenotypes and
      secondary types of hyperlipoproteinemia occurs according single algorithm. In
      aphysiological sense, the major mass of palmitic and oleic lipoproteins with very
      low density absorb cells without transformation into lipoproteins with low
      density. Only linoleic and linolenic lipoproteins with very low density which are
      formed after binding of apoB-100 of triglycerides the same name and which are not
      much in blood acquire density of lipoproteins with low density physiologically.
      Under high content of triglycerides in blood main mass of lipoproteins with low
      density consists of aphysiologic palmitic lipoproteins with very low density with
      hydrated density lipoproteins with low density, the cause of hyperlipoproteinemia
      of phenotype III is genotype e21e2 apoE; hyperlipoproteinemia of phenotype V-
      genotype e4/e4 and probably toxic inhibition of activity (synthesis)
      phylogenetically late stearil-KoA-desaturase-2.

PMID- 25069221
TI  - [The new international criteria of cardiac infarction and highly sensitive
      troponins: new possibilities and new problems].
AB  - The article deals with short review of main provisions of international
      recommendations concerning new diagnostic criteria of cardiac infarction and
      algorithms of highly sensitive measurement of circulating concentrations of
      cardiac troponins. The particular attention is paid to methods of serial highly
      sensitive measurement of levels of troponins making it possible to confirm or to
      exclude cardiac infarction during 1-3 hours after admission of patient. The
      perspectives and problems related to implementation of highly sensitive troponins
      into common practice of laboratory diagnostic are discussed.

PMID- 25069222
TI  - [The molecular genetic diagnostic of Gaucher disease type I].
AB  - The Gaucher disease is a hereditary enzymopathy underlaid by deficiency of
      activity of acidic beta-glycosidase, a lysosomal enzyme participating in
      degradation of products of cell metabolism. The actual study was carried out to
      characterize genotypes of patients with Gaucher disease in the Russian
      Federation. The study group consisted of sampling of 122 adult patients with
      Gaucher disease type I. The technique of allele-specific polymerase chain
      reaction in real time was applied to screening for detection of four most
      frequent mutations of gene of acidic beta-glycosidase (N370S, 84GG, L444P, IVS2+
      1). The results of molecular genetic studies demonstrated that in Russian
      patients the most frequent is mutation N370S and genotype N370S/other mutation.
      The second allele is presented by mutation not included into number of most
      frequent mutations of gene of acidic beta-glycosidase.

PMID- 25069223
TI  - [The comparative characteristic of two methods of detection of mutations of beta
      globin gene].
AB  - Nowadays, two methods of detection of mutations of beta-globin gene are applied:
      amplification of refractory mutation system and reverse dot-blot-hybridization.
      The study was implemented to comparatively analyze effectiveness of these methods
      of molecular diagnostic in detection of thalassemic mutations in Azerbaijan. The
      examined sample consisted of 82 patients with both homozygous and heterozygous
      thalassemia and drepanothalassemia as well. In examined patients 146 mutant
      alleles were detected; 132 were thalassemic ones (16 various mutations) and 14
      ranked among hemoglobinosis S (cod6(A>T)). The comparison of effectiveness of
      mentioned methods made it possible to conclude that both compared methods fit the
      diagnostic of thalassemic mutations. However the method of inverse dot-blot
      hybridization has a number of advantages and is the best choice for Azerbaijan.

PMID- 25069224
TI  - [The diagnostic value of serological and molecular genetic methods in detection
      of German measles disease].
AB  - The early diagnostic of German measles infection, especially in cases requiring
      differential diagnostic search, the most informative and usable in practice test
      systems are needed to be applied. The sampling of patients (n = 37) included
      males aged from 15 to 21 year (average age - 18 years) were admitted to hospital
      on 1-3 day from onset of disease. The technique of polymerase chain reaction with
      reverse transcription was applied to detect presence of viral RNA in
      nasopharyngital smear. The presence of viral RNA was confirmed in 26 examined
      patients (70%). The serological markers of onset of disease at the moment of
      first examination had 24 (65%) out of 37 patients. It is demonstrated that
      technique of polymerase chain reaction with reverse transcription has the most
      diagnostic value in confirmation of diagnosis of German measles infection at the
      first days of disease. In the sequel, the informativeness of methods of
      serological diagnostic will increase because complex application of methods of
      IgM and polymerase chain reaction with reverse transcription are needed at
      different periods of disease.

PMID- 25069225
TI  - [The advantages of dynamic evaluation of measurement quality in clinical
      diagnostic laboratory].
AB  - The national standard of laboratory quality control is based on a assumption
      about normal distribution of random error. The data of procedure of quality
      control get from analyzer Flexor XL during three months period were examined. The
      distributions of random error were non-Gauss ones in almost half of all examined
      tests by reason of both abnormal asymmetry and excess. To prevent possible
      clinical mistakes the actual level of quality is to be evaluated using dynamic
      values of bias, variation coefficient and o-metrics based on simple consecutive
      means. The most appropriate time of averaging consisted about 10 days and had no
      dependencies of type of test. The actual standard cab y easily improved taking
      into account the discovered advantages and simplicity of proposed approach.

PMID- 25069226
TI  - [The clinical biochemistry of hypo-lipedemic therapy and mechanisms of action of
      statins: the fatty acids, statins and diabetes mellitus].
AB  - In liver statins inhibit synthesis of specific pool of cholesterol which is
      formed de novo by hepatocytes for monolayer of polar lipids at the surface of
      forming lipoproteins of very low density. The statins, decreasing content of non
      esterified cholesterol in monolayer, activate hydrolysis of triglycerides in
      lipoproteins of very low density, formation of lipoproteins of low density and
      their absorption by cells through apoB-100 receptors. The statins, activating
      absorption of lipoproteins of low density, restore functional action of essential
      polyenoic fatty acids. The essential polyenoic fatty acids, fibrates and
      glitazones form in cells effective oleic version of metabolism when
      mitochondrions predominantly oxidize oleic fatty acid. The statins, non
      activating oxidation in peroxisomes and inhibiting activity of stearil-KoA
      desaturase, form in cells less effective palmitic variant of metabolism of fatty
      acids under oxidation of palmitic fatty acid in mitochondrions. The fatty acids
      are not enough under hydrolysis of exogenous triglycerides to synthesize optimal
      amount of ATP. The fatty acids accumulated in adipocytes are to be used. This is
      the cause of formation by statins the resistance to insulin. Functionally,
      lipoproteins of very low density and lipoproteins of low density are
      phylogenetically different. The former ones transfer fatty acids to cells in the
      form of triglycerides and the latter ones--in the form of ethers with alcohol
      cholesterol. The statins normalize absorption of essential polyenoic fatty acids
      by cells which manifest a physiological action named a pleotropic one.

PMID- 25069227
TI  - [The evaluation of ratio of oncomarkers in search of initial focus of tumor: on
      the occasion of fiftieth anniversary of discovery of alpha-fetoprotein as an
      oncomarker].
AB  - The article presents research data testifying the dominant value of HAFP behavior
      in diagnostic of oncological diseases. The importance of study of profile of main
      oncomarkers in patient is demonstrated. The method of hydrohelium biochips,
      developed in the institute of molecular biology, was used to determine 9 key
      oncomarkers. The application of this method made it possible to essentially
      complete the information map in 8 patients according to clinical interpretation
      of disease. In economically justified variant, this method is able to shorten
      period of study of patient, to specify character of pathological process and to
      transfer examination load of patients to the out-patient level.

PMID- 25069228
TI  - [The polymorphism of genes of synthesis and metabolism of estrogens and the risk
      of breast cancer].
AB  - The genetic polymorphism of enzymes of synthesis and metabolism of estrogens can
      input into predisposition to breast cancer. The purpose of actual study was to
      analyze the associations of polymorphic loci CYP17/B1rs10556836, CYP1A
      1rs1048943, CYP1A2rs762551, CYP19A1rs2470152 and CYP17A1rs743572 with risk of
      development of breast cancer in Russian residents of the Western-Siberian region
      of Russia. The rates of alleles and genotypes of the given loci were determined
      in sampling of women suffering with breast cancer (n = 670 females) and in
      control group (480 females without oncological diseases). The sub-groups of
      patients with breast cancer in pre-menopause--and post-menopause were analyzed
      separately. The border-line association of locus CYP17A1rs743572 is demonstrated
      with increasing of risk of breast cancer during pre-menopause (allele C: p =
      0.04). Among the rest of polymorphic loci no association was detected.

PMID- 25069229
TI  - [The dynamics and prognostic value of cerebral natriuretic peptide and C-reactive
      protein under acute cardiac infarction depending on tactic of treatment].
AB  - The sampling consisted of 102 patients with acute cardiac infarction with ST
      elevation up to 6 hours from the onset of disease. The subjects were divided into
      three groups: group I with primary stent procedure, group II with deferred stent
      procedure during 24 hours after effective thrombolytic therapy and group III with
      isolated effective thrombolytic therapy. The Doppler-echocardiography was applied
      to all patients. In every group the evaluation was carried out to dynamics NT
      proBNP and C-reactive protein. In group III with isolated effective thrombolytic
      therapy in sub-acute period of cardiac infarction NT-proBNP increased more than
      twice in comparison with groups of patients with stent procedure. The values of C
      reactive protein were lower than in groups I and II. The dynamics of NT-proBNP
      and C-reactive protein depend on mode of regeneration of coronary blood flow and
      level of increase of NT-proBNP corresponds the type of diastolic dysfunction of
      left ventricle of heart.

PMID- 25069230
TI  - [The clinical diagnostic importance of detection of vascular endothelial growth
      factor in evaluation of progression of pyelonephritis in children].
AB  - The article deals with evaluation of clinical diagnostic importance of detection
      of vascular endothelial growth factor under pyelonephritis in children. The study
      was implemented on sampling of 60 patients with various degree of compensation
      process. The level of vascular endothelial growth factor increased significantly
      in patients proportionally to severity of process and its value correlated with
      velocity of glomerular filtration and vascularization of kidney.

PMID- 25069231
TI  - [The difference of conformation of apoB-100 in lipoproteins of low and very low
      density. The modified lipoproteins and destructive inflammation in intima of
      arteries: a lecture].
AB  - The formation of ligand occurs in phylogenetically earlier lipoproteins of very
      low density and later lipoproteins of very low density when apoB- 100 takes
      active conformation in association with essential polyenoic fatty acids, in form
      of ethers with alcohol cholesterol, palmitic and oleic triglycerides. In
      lipoproteins of low density apoB-100-domain-ligand is formed, in lipoproteins of
      very low density apoE/B-100-ligand is formed. The ligand lipoproteins absorb
      cells using apoE/B-100 and apoB-100 receptor endocytosis. In cases of excess of
      palmitic triglycerides. and lipoproteins of very low density of the same name in
      blood, damage of primary structure of post-heparin, hepatic lipoprotein lipase
      and co-enzymes apoC-II and apoC-II, phenotype E2/E2 blood accumulates pre-ligand
      lipoproteins rich in triglycerides. In case of pathology of apoB-100-receptor
      post-ligand lipoproteins of low density with low content of triglycerides are
      cumulated. All non-ligand lipoproteins in a physiological way denature
      neutrophils. The presence of pathology induces modification in case of action of
      other agents (glyco-toxins). The pre-lipoproteins form in the intima of arteries
      soft voluminous plaques and such destructive inflammatory process as athero
      thrombosis. The post-lipoproteins form flat plaques and destructive inflammatory
      atheromatosis. The atherosclerosis can be labeled as disease ofconformation. The
      surplus of palmitic saturated fatty acids in food, phenotype E2/E2 and deletion
      of gene apoB-100-receptor are causes of intima lesion. The non-ligand
      lipoproteins form destructive process, dying foam cells and macrophages-
      inflammatory component. The atheromatosis is a result of realization of
      biological function of endoecology, support of "purity" of intercellular medium.

PMID- 25069232
TI  - [The evaluation of oxidative modification of proteins in patients with chronic
      disseminated dermatosis].
AB  - The analysis was made concerning oxidative modification of proteins of blood
      serum and erythrocytes in patients with chronic disseminated dermatosis. The high
      degree of total oxidative modification of proteins was established in patients
      with psoriasis and atopic dermatitis. The increase of level of oxidized
      derivatives of apoproteins in compound of lipoproteins of low density under
      psoriasis, atopic dermatitis and pemphigus was detected The increase of amount of
      carbonyl derivative of oligopeptids under psoriasis was revealed. In patients
      with resistance to applied therapy the statistically significant decrease of
      total oxidative modification of proteins of blood serum and erythrocytes was
      detected. This occurrence is possibly related to derangement of process of
      proteolytic destruction of proteins.

PMID- 25069234
TI  - [The diagnostic of chronic infection Helicobacter pylori in children].
AB  - The epidemiological studies testify an extremely high prevalence of chronic
      infection of children with Helicobacter pylori in Russia. The affection consists
      from 50% to 80% depending on region and age of examined children. The currently
      in force recommendations "Maastricht IV" concerning diagnostic and treatment of
      Helicobacter pylori infection adult patients are applied not in its fullness to
      children adolescent population. At the same time recently published joint
      conciliatory document of the European and North American associations of
      pediatric gastroenterologists is oriented to populations with low prevalence of
      Helicobacter pylori infection and particular profile of drug resistance. Hence,
      an urgent need exists to develop modern local algorithm concerning diagnostic,
      treatment and control of eradication of Helicobacter pylori infection among
      children and adolescents in Russia. The review presents analysis of admissibility
      of application in Russia's conditions of the international conciliatory documents
      concerning diagnostic of Helicobacter pylori infection in children. The data from
      conciliatory document of the European (ESPGHAN) and North American (NASPGHAN)
      associations of pediatric gastroenterologists, particular orginal research
      studies and one's own clinical experience were used. The advantages and
      shortcomings of actual methods of laboratory diagnostic of Helicobacter pylori
      infection are discussed. The approaches to application of particular diagnostic
      methods are considered. The enhanced indications to detection of infection and
      implementation of eradication therapy are proposed.

PMID- 25069233
TI  - [The condition of the system "peroxide oxidation of lipids-antioxidant defense"
      in mixed saliva of patients with chronic generalized periodontitis].
AB  - The comparative analysis was made concerning conditions of the system "Peroxide
      oxidation of lipids-antioxidant defenses in mixed saliva of patients with chronic
      disseminated periodontitis of light (n = 45), mean (n = 36) and severe (n = 18)
      degrees. The control group consisted of 25 clinically healthy persons with intact
      periodontium. The study revealed that in comparison with control group, in
      patients with chronic disseminated periodontitis occurred an increasing of
      content of heptane-soluble diene conjugates, isopropanol-soluble ketodienes and
      conjugated trienes, ceruloplasmin and a decreasing of level of alpha-tocopherol,
      especially under severe degree of disease. The study also established a non
      linear U-dependence between indicators of the system "Peroxide oxidation of
      lipids-antioxidant defenses" in mixed saliva and severity of affection of tissues
      of periodontium in patients with chronic disseminated dermatosis.

PMID- 25069235
TI  - [The rate of detection and diagnostic significance of antibodies to Borrelia
      burgdorferri in patients with eyes diseases of inflammatory nature].
AB  - The eyes diseases appear at any stage of Lyme borreliosis and clinical
      manifestations are polymorphic and non-specific. The study examined prevalence of
      B. burgdorferi s.l. infection in patients with different eyes diseases and
      evaluated diagnostic significance of antibodies to B. burgdorferi in clinical
      practice. The sampling included 57 patients with conjunctivitis, keratitis,
      uveitis, choreoretinitis, optical neuritis of unclear etiology. The blood serum
      of patients was analyzed to detect presence of IgM- and IgG-antibodies to B.
      burgdorferi s.l. The positive results were confirmed in Western blot (two-sweep
      method). The immune enzyme analysis detected antibodies to B. burgdorferi in 7
      out of 57 examined patients (12.3%). The Western blot confirmed presence of
      antibodies only in 3 serums out of 57 (5.3%). The high rate of false positive
      results was established during immune enzyme analysis detecting IgM-antibodies to
      B. burgdorferi. On the basis of comprehensive examination ophtalmo-borreliosis
      was diagnosed in two out of three patients seropositive to B. burgdorferi. In one
      seropositive patient co-infection B. burgdorferi provoked exacerbation of chronic
      uveitis of unclear etiology. It is appropriate to include in plan of examination
      of patients with inflammatory eyes diseases of unclear genesis the detection of
      antibodies to B. burgdorferi using two-sweep test (study of serums with immune
      enzyme analysis, confirmation of positive results in Western blot).

PMID- 25069236
TI  - [The shortcomings of technical regulation in sphere of circulation of medical
      devices for diagnostic in vitro in the Russian Federation: the state of affairs
      and proposed solutions].
AB  - The article presents analysis of international and national trends in area of
      development of normative legal documents in sphere of circulation of medical
      devices for diagnostic in vitro. The comparative analysis was made concerning
      certain principles of formation of nomenclature of medical devices for diagnostic
      in vitro in the international practice and in the Russian Federation. The
      necessity of reformation of national normative legal base in this issue is
      demonstrated.

PMID- 25069237
TI  - [About the monograph "Screening and differentiated cytomorphologic diagnostic of
      cervix cancer" by V.I. Novik].

PMID- 25069238
TI  - Enhanced depressive-like behaviors after Toll-like receptor 7 stimulation in
      mice.
AB  - Toll-like receptor (TLR) 7 recognizes viral single-stranded RNA and triggers anti
      viral immune responses through the production of type I interferons (IFNs) IFN
      alpha and IFN-beta. IFN-alpha is known to induce various psychiatric changes such
      as depressive symptoms; however, the correlation with TLR7 activation remains to
      be determined. In this study, we examined the effect of imiquimod, a TLR7
      specific ligand, on depressive-like behaviors evaluated by the forced swim test
      (FST) and the tail suspension test (TST) in mice. Immobility durations were
      significantly prolonged in both FST and TST by 2 h after imiquimod treatment (50
      microg/body, i.p.), indicating that TLR7 activation enhanced depressive-like
      behaviors in mice. In addition, imiquimod induced IFN-alpha mRNA expression in
      the hippocampus, whereas it prevented long-term potentiation in the Schaffer-CA1
      pathway (i.e., hippocampal synaptic plasticity). Moreover, TLR7 mRNA expression
      in the hippocampus was higher than that in the whole brain. These findings
      suggest that TLR7 activation enhances depressive-like behaviors in mice, possibly
      through increasing IFN-alpha expression and altering synaptic plasticity in the
      hippocampus.

PMID- 25069239
TI  - Involvement of sigma 1 receptor in the SSRI-induced suppression of the
      methamphetamine-induced behavioral sensitization and rewarding effects in mice.
AB  - The abuse of methamphetamine causes abnormal behaviors which are
      indistinguishable from schizophrenia in humans. Recent reports have shown that
      selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on
      methamphetamine-related behaviors, including behavioral sensitization and
      rewarding effects in animals. However, the exact mechanisms by which SSRIs affect
      methamphetamine-related behaviors are not yet clear. The present study was
      designed to investigate the effects of SSRIs on the development of
      methamphetamine-induced behavioral sensitization and rewarding effects in mice.
      Behavioral sensitization was measured by examining the locomotor activity of mice
      in a tilting cage after repeated injections of methamphetamine. Repeated
      administration of methamphetamine significantly induced a behavioral
      sensitization. Some SSRIs (fluoxetine and fluvoxamine), which have sigma-1
      receptor agonistic activity, inhibited the development of methamphetamine-induced
      behavioral sensitization. Fluoxetine also dose-dependently attenuated the
      rewarding effects of methamphetamine as measured by the conditioned place
      preference paradigm. Furthermore, the sigma-1 receptor antagonist NE-100
      significantly reversed the inhibitory effects of fluoxetine on methamphetamine
      induced behavioral sensitization and rewarding effects. These results suggest
      that sigma-1 receptor agonistic activity might be involved in the attenuating
      effects of fluoxetine and fluvoxamine on methamphetamine-induced behavioral
      sensitization and rewarding effects.

PMID- 25069241
TI  - [The interaction between serotonergic and cannabinoidergic modulations involved
      in the fear extinction].
AB  - In the amygdala, it has been demonstrated that cannabinoid CB1 receptors are
      particularly enriched in GABAergic axon terminals and moderately expressed on
      glutamatergic fibers, and involved in the fear coping strategies. In this study,
      we found predominant neuronal projections of serotonergic, dopaminergic and
      cholinergic fibers in the basolateral amygdala (BA), and CB1 receptors were
      frequently localized on serotonergic axons but not dopaminergic, noradrenergic or
      cholinergic fibers. Furthermore, extracellular release of serotonin was
      significantly reduced by WIN55212-2, a CB agonist, whereas dopamine concentration
      was not altered, indicating presynaptic serotonin release is modulated by CB1
      receptors. On the other hand, alpha-methyl-5-HT, 5-HT2 receptor agonist decreased
      the evoked IPSC and EPSC amplitude accompanied with enhancement of paired pulse
      ratio and induced inward currents from the patch-clamp recording BA pyramidal
      neurons; these are parameters of presynaptic effect and postsynaptic localization
      of 5-HT2 receptors, respectively. This suppression of IPSC amplitude was
      completely blocked by MDL100907, a 5-HT(2A) antagonist, or AM251, a CB1
      antagonist. These findings suggest that endocannabinoid is synthesized via
      activation of postsynaptic 5-HT(2A) receptors, and regulates not only inhibitory
      presynaptic GABA release but also local serotonergic transmission in the BA.

PMID- 25069242
TI  - [Significance of the pharmacotherapy of schizophrenia in the emotional context
      processing of cognition].
AB  - Emotional disorders and cognitive dysfunctions are important treatment targets in
      psychiatric clinical settings. The biological mechanisms of emotional disorders
      have been studied with methods that include fear conditioning, schizophrenia
      models are studied with methamphetamine-induced reverse tolerance in rats, and
      dynamic changes in brain neurotransmitters are studied with microdialysis and
      high-performance liquid chromatography. We combined these methods in order to
      evaluate dopamine dynamics in the amygdala and the biological bases and
      relationships of emotional disorder and cognitive dysfunction. Fear-conditioned
      rats showed freezing behavior and dopamine release in the amygdala in response to
      conditioned stimuli. Methamphetamine-induced reverse tolerance rats showed
      increased dopamine release in the amygdala in response to conditioned stimuli.
      The increased release of dopamine continued after the freezing behavior had
      ended. This increased and long-lasting dopamine release may reflect abnormal
      emotional context processing in cognition in schizophrenia. Antipsychotic drugs,
      such as haloperidol, aripiprazole, and clozapine, suppress this increased release
      of dopamine in the amygdala in response to conditioned stimuli. These findings
      suggest that antipsychotic drugs may stabilize abnormal emotional context
      processing in cognition in this model. We conclude that the significance of
      pharmacotherapy in schizophrenia is that antipsychotic drugs stabilize the
      emotional context processing in cognition and adjust the relationship of emotion
      and cognition.

PMID- 25069243
TI  - [Childhood stress and depression].
AB  - Genetic factors, personality and environmental factors contribute to the onset of
      major depression in a classic model. Since the 1980s, several retrospective
      studies have reported that childhood stress or trauma experiences occur more
      often in major depressive patients than in healthy controls. However,
      retrospective studies have a limitation: there is the possibility that depressed
      individuals may evidence an increased likelihood to recall negative events from
      their past. In 2003, Caspi et al. reported the prospective cohort study of the
      birth cohort in Dunedin, New Zealand, in which individuals with one or two copies
      of the short allele of the 5-HTT promoter polymorphism exhibited more depressive
      symptoms, diagnosable depression, and suicidality in relation to stressful life
      events (childhood maltreatment and adult stressful life events) than individuals
      homozygous for the long allele. This epidemiological study provided evidence of a
      gene-by-environment interaction (G x E interaction), in which an individual's
      response to environmental insults is moderated by his or her genetic makeup.
      Several studies of major depression reported that childhood stress or abuse
      increases the hypothalamic-pituitary-adrenal axis function and is related to low
      volume of the hippocampus and anterior cingulate. The authors examine the
      influence of childhood stress, adult life events and temperament on depression
      and anxiety in normal adults and mood disorder patients in this study.

PMID- 25069244
TI  - [Treatment of posttraumatic stress disorder and extinction learning of traumatic
      memory].
AB  - Posttraumatic stress disorder (PTSD) is a debilitating psychological condition
      that develops following exposure to a traumatic event. The characteristic
      symptoms of PTSD are re-experience, avoidance, psychic numbing and hyper-arousal.
      The biological PTSD literature has been dramatically growing over the past three
      decades. PTSD symptoms related to re-experiencing the traumatic event may be
      conceptualized within a fear conditioning framework. Recent findings suggest that
      PTSD is associated with a failure of extinction learning of an acquired fear
      response. A fear-circuit model of PTSD posits that vmPFC fails to inhibit the
      amygdala, which has a crucial role in fear learning. Exposure therapy currently
      has the largest number of randomized clinical trials demonstrating its efficacy,
      and is recommended with substantial clinical confidence in treatment guidelines
      for PTSD. The efficacy of Prolonged Exposure (PE) was also shown for Japanese
      PTSD patients in a randomized controlled trial (Asukai et al., 2010). The
      emotional processing theory that accounts for the treatment mechanism of PE may
      be consistent with the hypothesis of a neurobiological mechanism in PTSD. D
      cycloserine (DCS), an NMDA partial agonist, has been shown to facilitate
      extinction learning in animals and humans. Clinically, DCS has been shown to be a
      promising augmentation to PE, particularly for those who need longer treatment.

PMID- 25069246
TI  - [From pathogenesis to treatment of genetic intellectual disabilities: a lesson
      from Angelman syndrome research].
AB  - Angelman syndrome (AS) is characterized by severe intellectual disability,
      epilepsy and ataxic motor dysfunction. Paternally imprinted UBE3A, which is
      located in the imprinted domain of 15q11-q13, is the causative gene of AS. UBE3A
      is exclusively expressed from the maternally inherited allele only in neurons
      (neuron-specific imprinting), and is regulated by antisense RNA. UBE3A is an E3
      ubiquitin protein ligase and Arc is one of its targets in the brain. Arc is known
      to regulate AMPA-type glutamate receptor at the post-synaptic membrane. Loss-of
      function of UBE3A results in upregulation of Arc and downregulation of AMPA
      receptors, giving rise to disturbance in experience-dependent synaptic
      plasticity. Unraveling the pathophysiology of AS will shed light on the
      development of pharmaceutical agents for genetic intellectual disabilities.
      Recently, topoisomerase inhibitors were shown to unsilence imprinted Ube3a in a
      mouse model of AS. This success indicated the possibility of an epigenetic
      therapy for AS. Therefore, AS is also a good model for the development of
      epigenetic therapy for genetic intellectual disorders caused by epigenetic
      dysfunction.

PMID- 25069245
TI  - [Proposal of endogenous anticholinergic hypothesis in Alzheimer disease].
AB  - We previously speculated that anticholinergic activity (AA) endogenously appeared
      in Alzheimer's disease (AD) and accelerated AD pathology. In this article we
      introduce manuscripts supporting the endogenous appearance of AA in AD and the
      acceleration of AD pathology. We speculate that acethylcholine (ACh) not only is
      related to cognitive functions but also regulates the inflammatory system.
      Therefore in AD, in which the ACh system is down-regulated, the hyperactivity of
      the inflammatory system may be caused and among cyctokines, substances having
      anticholinergic properties may appear. We also refer to a case in which serum
      anticholinergic activity (SAA) disappeared with the prescription of memantine (an
      antidementia agent that has the property of the N-methyl-D-aspartate (NMDA)
      receptor blocker) and speculate that because the hyperactivity of the
      inflammatory system occurs by way of the hyperactivity of NMDA receptor,
      memantine could abolish the AA.

PMID- 25069247
TI  - [The behaviors of proliferative cells in the subventricular zone during cortical
      development].
AB  - Recent studies revealed that the subventricular zone (SVZ) in the developing
      mammalian cerebrum is a source of cortical neurons along with the ventricular
      zone (VZ), and especially in human SVZ, abundant self-renewal stem cells exist
      and are thought to largely contribute to the development of huge brain. These
      studies suggested that the regulations of the number of progenitors or stem cells
      in the SVZ and their stemness are important issues for understanding the final
      output of the cortical neurons. We previously reported the migratory difference
      between the direct progeny of the VZ and the further dividing cells in the SVZ in
      mice. The former population finishes the cell division in the VZ, stays there for
      more than 10 hours, and then accumulates in the lower SVZ as multipolar cells.
      The other exits the VZ earlier than former, distributes widely in the SVZ and
      divides. These observations showed that the SVZ is divided into two regions; the
      lower postmitotic cell accumulation region and upper dividing cell-rich region.
      This model provides the framework for understanding the nature of the SVZ.

PMID- 25069248
TI  - [Synapse elimination and functional neural circuit formation in the cerebellum].
AB  - Neuronal connections are initially redundant, but unnecessary connections are
      eliminated subsequently during postnatal development. This process, known as
      'synapse elimination', is thought to be crucial for establishing functionally
      mature neural circuits. The climbing fiber (CF) to the Purkinje cell (PC) synapse
      in the cerebellum is a representative model of synapse elimination. We disclose
      that one-to-one connection from CF to PC is established through four distinct
      phases: (1) strengthening of a single CF among multiple CFs in each PC at P3-P7,
      (2) translocation of a single strengthened CF to PC dendrites from around P9, and
      (3) early phase (P7 to around P11) and (4) late phase (around P12 to P17) of
      elimination of weak CF synapses from PC somata. Mice with PC-selective deletion
      of P/Q-type voltage-dependent Ca2+ channel (VDCC) exhibit severe defects in
      strengthening of single CFs, dendritic translocation of single CFs and CF
      elimination from P7. In contrast, mice with a mutation of a single allele for the
      GABA-synthesizing enzyme GAD67 have a selective impairment of CF elimination from
      P10 due to reduced inhibition and elevated Ca2+ influx to PC somata. Thus,
      regulation of Ca2+ influx to PCs is crucial for the four phases of CF synapse
      elimination.

PMID- 25069249
TI  - [Localization and functions of the D-neuron: significance in pathogenesis of
      schizophrenia].
AB  - The author proposes the "D-cell hypothesis" for molecular basis of the mesolimbic
      dopamine (DA) hyperactivity of schizophrenia. D-neurons, which were defined as
      "non-monoaminergic aromatic L-amino acid decarboxylase (AADC)-containing cells",
      produce trace amines (TAs), such as tyramine, phenylethylamine (PEA) and
      tryptamine. D-neurons may also take up amine precursors, and may convert them to
      amines by decarboxylation. The author's preliminary report showed that the number
      of AADC-containing neurons, that is D-neurons, was reduced in the striatum and
      nucleus accumbens of patients with schizophrenia. TA-associated receptor type 1
      (TAAR1) has been shown to have a number of ligands, such as tyramine, PEA,
      methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and lysergic acid
      diethylamide (LSD), that may change human mental states. In patients with
      schizophrenia, the reduction of striatal D-neurons and possible decrease of
      striatal TA, is caused by neural stem cell dysfunction in the subventricular zone
      of the lateral ventricle. The reduced stimulation of TAAR1 on terminals of
      ventral tegmental area (VTA) DA neurons increases the firing frequency of VTA DA
      neurons, as recently published reports have shown, resulting in mesolimbic DA
      hyperactivity. In addition, increased DA D2 receptor stimulation, caused by
      striatal DA hyperactivity, may suppress forebrain neural stem cell proliferation,
      and would cause an additional decrease of D-neurons.

PMID- 25069250
TI  - [Perinatal innate immune activation and neuropsychological development].
AB  - Development of animal models is a crucial issue in biological psychiatry for the
      search of novel drug targets as well as the screening of candidate compounds.
      Epidemiologic studies suggest that environmental insults, such as prenatal
      infection and perinatal complication, are involved in the development of
      schizophrenia. Recently, we have developed a novel mouse model of viral infection
      during the perinatal stage by injecting polyriboinosinic-polyribocytidilic acid
      (polyI:C) into neonatal mice. Neonatal treatment of mice with polyI:C, an inducer
      of innate immune responses via toll-like receptor 3, caused a significant
      increase in interferon-induced transmembrane protein 3 (IFITM3) levels in the
      astrocytes of the hippocampus, which resulted in long-lasting brain dysfunction,
      including cognitive and emotional impairments as well as a deficit in
      depolarization-evoked glutamate release in the hippocampus in adulthood. Neonatal
      polyI:C-induced neuronal impairments have not been observed in IFITM3-KO mice.
      These findings suggest that the induction of IFITM3 expression in astrocytes by
      the activation of the innate immune system during the early stages of
      neurodevelopment has non-cell autonomous effects that affect subsequent
      neurodevelopment, leading to neuropathological impairments and brain dysfunction,
      by impairing endocytosis in astrocytes.

PMID- 25069251
TI  - [Genetic vulnerability of methamphetamine dependence].
AB  - Methamphetamine (METH) dependence show strong familial and genetic influences in
      family and twin studies. METH exerts its reinforcing effects by modulating
      monoaminergic transmission, of which dopamine is supposed to be important.
      Previously, experimental animals were being used to identify mechanisms of action
      of METH that are related to its abuse and toxicity, and genetic mouse models have
      also been used to define genes that may predict risk for the development of drug
      addiction. We found that genetic variances of dopamine transporter, dopamine
      receptor, micro-opioid receptor, serotonin 1A receptor, serotonin 6 receptor, and
      adenosine 2A adenosine receptor could be vulnerability factors for METH
      dependence or psychosis in the Japanese population. Genetic analysis with a
      genome-wide association study (GWAS)-based approach has been successful for
      investigating the genetic influences of METH dependence and other complex
      features. Collaborative studies with JGIDA and NIDA/NIH have obtained the results
      that the genetic vulnerability to METH dependence contributes to other major drug
      addiction. The genetic studies for METH dependence might help to identify the
      risk of individuals and to develop treatments that take advantage of individual
      genetic information in the future.

PMID- 25069252
TI  - [Mechanisms of ethanol-induced type I IP3 receptor expression].
AB  - Ethanol has a variety of action on neuronal functions, though its mechanism of
      action remains uncertain. Previous investigations have demonstrated functional
      alteration of neurotransmitter receptors and ion channels by ethanol at its
      concentration observed in the blood of alcoholics. Our recent studies have shown
      that chronic ethanol treatment up-regulates high voltage-gated L-type calcium
      channels and ryanodine receptors, both of which regulate intracellular Ca2+
      concentration, and that the up-regulation of these calcium channels participates
      in behavioral changes including the rewarding effect. Among inositol 1,4,5
      trisphosphate receptors (IP3Rs) classified into three different subtypes (type 1
      (IP3R-1), type 2, and type 3 IP3Rs) with distinct physiological properties, IP3R
      1 is the major neuronal member in the central nervous system, predominantly
      enriched in cerebellar Purkinje cells and abundant in neurons in the cerebral
      cortex. Although the most important result of IP3R channel functions is the
      change in intracellular Ca2+ concentration and phosphorylation of IP3Rs, there
      are few available data on ethanol effect on IP3Rs. In this report, we demonstrate
      the functional relationship between ethanol-induced rewarding effect and IP3R-1
      expression and regulatory mechanisms of IP3R-1 expression after chronic ethanol
      exposure, especially focusing on Ca(2+)-related signal transduction pathways via
      dopamine D1 receptors using mouse cerebral cortical neurons.

PMID- 25069254
TI  - [Haplotype analysis of GSK-3beta gene polymorphisms and smoking behavior].
AB  - In this study, the relationship between the haplotypes consisting of single
      nucleotide polymorphisms (SNPs) of GSK-3beta -50T/C and -1727A/T and the
      derivation of smoking was studied among 102 smokers and 103 non-smokers. It was
      shown that the GSK-3beta -50T/C polymorphism may be linked with the smoking.
      There is significantly lower T-allele frequency in the smokers than non-smokers
      (chi2 (2) = 21.01, P = 0.000027; chi2 (1) 13.28, P = 0.00026). According to
      haplotype analysis, there was an association between smokers and non-smokers
      (global P = 0.00029). Higher haplotype 1 (T-A) frequency was observed in non
      smokers than in smokers (P = 0.00036), whereas higher haplotype 2 (C-A) frequency
      was observed in smokers than in non-smokers (P = 0.000053). Pairwise D' and r2
      values between the two SNPs in this study were 0.51 and 0.042, respectively. The
      two SNPs showed weak linkage disequilibrium with each other. This study suggests
      that GSK-3beta -50T/C polymorphism and two haplotypes may be related to smoking
      behavior.

PMID- 25069253
TI  - [The role of a molecule associated with drug dependence, shati/nat8l].
AB  - Various molecules are involved in drug addiction induced by drugs of abuse.
      Therefore, the mechanism of drug addiction is still not clear, and it has been a
      difficulty in the development of preventive and curative drugs for drug
      dependence. We tried to identify the molecules associated with drug dependence,
      and found three molecules including shati/nat81. Recently, it has been
      demonstrated that the substrate for shati/nat81 is aspaltate and shati/nat8l
      biosynthesizes N-acetylaspartate, which exists abundantly in the mammalian brain.
      In this study, we investigated the physiological function of shati/nat81 and the
      role of shati/nat81 in drug dependence. The overexpression of shati/nat81 in the
      dorsal striatum of mice led to social abnormality and depression-like behavior,
      and worsened a part of the motor dysfunction induced by Ca2+ channel agonist BAY
      K 8644. The overexpression of shati/nat81 in the nucleus accumbens of mice
      inhibited methamphetamine-induced behavioral and biochemical abnormalities. These
      findings suggest that the shati/nat81-associated system could play a role in the
      regulation of mental activity and motor action, and be a new target in the
      development of therapeutic drugs for drug dependence.

PMID- 25069255
TI  - [Analysis of the cardiac side effects of antipsychotics: Japanese Adverse Drug
      Event Report Database (JADER)].
AB  - We analyzed the cases of side effects due to antipsychotics reported to Japan's
      Pharmaceuticals and Medical Devices Agency (PMDA) from Jan. 2004 to Dec. 2012. We
      used the Japanese Adverse Drug Event Report Database (JADER) and analyzed 136 of
      216,945 cases using the defined terms. We also checked the cardiac adverse
      effects listed in the package inserts of the antipsychotics involved. We found
      cases of Ikr blockade resulting in sudden death (49 cases), electrocardiogram QT
      prolonged (29 cases), torsade de pointes (TdP, 19 cases), ventricular
      fibrillation (VF, 10 cases). M2 receptor blockade was observed in tachycardia (8
      cases) and sinus tachycardia (3 cases). Calmodulin blockade was involved in
      reported cardiomyopathy (3 cases) and myocarditis (1 case). Multiple adverse
      events were reported simultaneously in 14 cases. Our search of package inserts
      revealed warnings regarding electrocardiogram QT prolongation (24 drugs),
      tachycardia (23), sudden death (18), TdP (14), VF (3), myocarditis (1) and
      cardiomyopathy (1). We suggest that when an antipsychotic is prescribed, the
      patient should be monitored regularly with ECG, blood tests, and/or biochemical
      tests to avoid adverse cardiac effects.

PMID- 25069256
TI  - [Analysis of dopamine transporter knockout mice as an animal model of AD/HD].
AB  - Attention deficit/hyperactivity disorder (AD/HD) is characterized by significant
      difficulties of inattention and/or hyperactivity and impulsiveness. Dopamine
      transporter (DAT) knockout (KO) mice have been suggested to constitute an animal
      model of AD/HD. DAT KO mice exhibit persistently and profoundly elevated
      extracellular dopamine levels in the striatum and nucleus accumbens. These mice
      display numerous behavioral alterations that model aspects of AD/HD that include
      hyperactivity in novel environments and impulsivity. Both hyperactivity and
      impulsivity can be ameliorated by treatment with methylphenidate and nisoxetine.
      These drugs increase extracellular dopamine and norepinephrine levels in the
      prefrontal cortex. It is likely that methylphenidate and nisoxetine activate the
      prefrontal catecholamine systems by blocking the norepinephrine transporter (NET)
      function, thereby helping to improve AD/HD-like behavior in DAT KO mice.

PMID- 25069257
TI  - [Reconsideration of nicotine and other substance dependence: a clue from
      dependence-related mentation including reward, motivation, learning, delusion and
      hallucination toward understanding the concept of non-substance-related
      addiction].
AB  - Nicotine produces core symptoms of substance dependence (craving and withdrawal)
      without any psychotic symptoms. The psychopharmacological structure of craving is
      hypothesized to be constituted by three components: the primary reinforcing
      property of a substance, the secondary reinforcing property of that substance
      (conditioned aspects of the environment, such as contextual or specific cues
      associated with substance taking), and the negative affective motivational
      property during withdrawal (i.e. the desire to avoid the dysphoric withdrawal
      symptoms elicits craving). Among the three components, the primary reinforcing
      property of a substance forms the most fundamental factor for establishing
      substance dependence. Sensitization or reverse tolerance observed in locomotor
      activity of animals, which had been believed to be a methamphetamine psychosis
      model, is demonstrated to reflect the establishment of conditioned reinforcement.
      Finally, non-substance-related addiction such as gambling, internet, and sex is
      discussed. From the aspect of the above hypothetical psychopharmacological
      structure of craving, the most significant difference between substance
      dependence and non-substance-related addiction is that the primary reinforcing
      property of non-substance reward is relatively intangible in comparison with that
      of a substance of abuse.

PMID- 25069258
TI  - [Understanding of the psychiatry in palliative care: dysfunction of the rewarding
      system under the pain state associated with exacerbating pain].
AB  - Recent human brain imaging studies have examined differences in activity in the
      nucleus accumbens (N.Acc.) in response to heat stimuli between controls and
      patients with chronic pain, and have revealed that the N.Acc. plays a role in
      predicting the value of a noxious stimulus and its offset, and in the consequent
      changes in the motivational state. Nevertheless, the molecular mechanisms of
      change in the circuitry involved in emotion and motivation in response to chronic
      pain stimuli were not fully explored. On the other hand, it has been considered
      that micro RNAs (miRNAs) play important roles as key modulators of post
      transcriptional gene expression. We have reported that changes in miRNAs are
      associated with predicted changes in gene expression of candidate targets in the
      N.Acc. under neuropathic pain. Therefore, we have introduced a new insight into
      an epigenetic dysfunction of "mesolimbic motivation/valuation circuitry" under a
      neuropathic pain-like state. These findings raise intriguing possibilities that
      miRNA-modulating cellular events along with epigenetic modifications may be
      associated with neural plasticity and neuronal adaptive responses in mesolimbic
      motivation/valuation circuitry under which the neuropathic pain may induce
      negative emotions, exacerbating pain.

PMID- 25069259
TI  - [Genetic polymorphisms commonly associated with sensitivity to various addictive
      substances].
AB  - Opioids, such as morphine and fentanyl, are widely used as effective analgesics
      for the treatment of acute and chronic pain. In addition, the opioid system has a
      key role in the rewarding effects of morphine, ethanol, cocaine and various other
      drugs. The authors have focused on G-protein-activated inwardly rectifying
      potassium (GIRK) channel subunits, GIRK2 and GIRK3, which are important molecules
      in opioid transmission, and found that the SNPs within the GIRK2 and GIRK3 gene
      region were significantly associated with postoperative analgesic requirements,
      one of which was also associated with vulnerability to methamphetamine (METH)
      dependence. Further, by conducting a multistage genome-wide association study
      (GWAS) in healthy subjects, the authors found that the rs2952768 single
      nucleotide polymorphism (SNP) was strongly associated with the requirements for
      postoperative opioid analgesics after painful cosmetic surgery and consistent
      results were obtained in patients who underwent abdominal surgery. In addition,
      the SNP also showed significant association with vulnerability to severe drug
      dependence in patients with METH dependence, alcohol dependence, and eating
      disorders and a lower 'Reward Dependence' score on a personality questionnaire in
      healthy subjects. These outcomes provide valuable information for the
      personalized treatment of pain and drug dependence.

PMID- 25069260
TI  - [Synaptic plasticity and synaptic reorganization regulated by microglia].
AB  - Microglia are generally believed to be brain macrophages, which become phagocytic
      cells after cellular activation in response to inflammation or injury in the
      brain. However, accumulating evidence suggests that microglia modulate
      neurotransmission and synaptic plasticity by secretion of several soluble
      factors. Importantly, microglia secret glycine to enhance NMDA receptor-mediated
      responses and hippocampal long-term potentiation, a cellular basis of learning
      and memory. Although the expression of NMDA receptors was also observed in
      microglia, NMDA receptor-mediated responses were not induced in microglia. This
      suggests that NMDA receptors expressed in microglia are not functional. Besides
      the modulation of synaptic transmission, microglia also play an important role in
      synaptic remodeling by the pruning of unnecessary synapses and axon terminals
      during the postnatal developmental stage and adaptation to novel environments
      even in the healthy brain. Furthermore, we have recently found that clock genes
      in microglia drive P2Y12R and cathepsin S to regulate diurnal change in the
      synaptic activity. Therefore, defects in these microglial functions may
      eventually result in several brain diseases including neuropsychiatric disorders.

PMID- 25069261
TI  - [NMDA-type glutamate receptor and schizophrenia].
AB  - Reduced glutamate neurotransmission via the NMDA receptor has been hypothesized
      to be involved in the pathophysiology of schizophrenia chiefly based upon the
      following observations: (1) non-competitive and competitive antagonists for the
      NMDA receptor including phencyclidine mimic not only positive symptoms but also
      negative and cognitive symptoms of schizophrenia, (2) the rank order potency of
      schizophrenomimetic effects of NMDA receptor antagonists is strictly correlated
      with that of their NMDA receptor-current blocking efficacies, (3) non
      psychotomimetic doses of NMDA receptor antagonists for healthy controls produce
      psychotic symptoms in the remitted patients with schizophrenia, and (4) a
      schizophrenia-like psychotic state has often been reported in patients with
      encephalitis with anti-NMDA receptor antibody in the central nervous system. The
      possible NMDA receptor hypofunction could be caused by understimulation of its
      glycine site and/or by loss of NMDA receptor-possessing cells due to excess
      synaptic glutamate contents, or could lead to overactivation of the non-NMDA
      glutamate receptors. Therefore, agents for direct or indirect facilitation of the
      glycine site function or for attenuation of glutamate release have been studied
      to develop a novel pharmacotherapy for schizophrenia that could ameliorate both
      its antipsychotic-responsive and -resistant symptoms.

PMID- 25069262
TI  - [Anti-NMDA receptor antibody in systemic lupus erythematosus].
AB  - N-Methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels with crucial
      roles in synaptic transmission and central nervous system plasticity. Systemic
      lupus erythematosus (SLE) is a multi-system inflammatory disorder characterized
      by the presence of autoantibodies directed against double-stranded (ds) DNA. The
      pathophysiology of neuropsychiatric (NP) SLE is diverse and complicated. In SLE,
      anti-dsDNA antibody (Ab) cross-reacts with NMDA receptors. Serum anti-NMDA
      receptor Ab was found in 30% of SLE patients. We demonstrated the relationship
      between anti-NMDA receptor Ab and each organ's involvement in SLE, and the
      biological function of anti-NMDA receptor Ab. The frequency of NP-SLE was
      significantly higher in the anti-NMDA receptor Ab positive subset than the
      negative subset, although the frequencies of serositis and nephritis were not
      significant. Anti-NMDA receptor Ab titer inversely correlated with leukocyte
      counts and hemoglobin levels. Moreover, regarding to the effects of anti-NMDA
      receptor Ab on NMDA receptor-transfected cell viability and intracellular Ca2+
      level, there was a significant inverse correlation between anti-NMDA receptor Ab
      titer and cell viability, and a significant association between anti-NMDA
      receptor Ab titer and intracellular Ca2+ level. In conclusion, anti-NMDA receptor
      Ab is associated with NP-SLE and cytopenia. Anti-NMDA receptor Ab could cause the
      injury of NMDA receptor-expressed cells by increasing Ca2+ influx.

PMID- 25069263
TI  - [Multiaxial evaluation of the pathophysiology of mood disorder and therapeutic
      mechanisms of clinical drugs by neuronal plasticity and neuronal load].
AB  - Impairment of neuronal plasticity is important in the pathophysiology of mood
      disorder. Both zinc deficiency and social isolation impair neuronal plasticity.
      Both cause a depressive state. However, in experiments using animals, their
      combined loading induced manic-like behavior. Therefore, it was inferred that
      moderate impairment of neuronal plasticity induces a depressive state, and that
      further impairment of neuronal plasticity induces a manic state. However, some
      kind of load toward neuronal function through neural transmission can influence
      mood disorder symptoms without direct effects on neuronal plasticity. Our
      hypothesis is that mania is an aggravation of depression from the perspective of
      neuronal plasticity, and that multiaxial evaluation by neuronal plasticity and
      neuronal load through neural transmission is useful for understanding the
      pathophysiology of mood disorder. There are many clinical aspects that have been
      difficult to interpret in mood disorder: Why is a mood stabilizer or electric
      convulsive therapy useful for both mania and depression? What is the
      pathophysiology of the mixed state? Why does manic switching by an antidepressant
      occur or not? Our hypothesis is useful to understand these aspects, and using
      this hypothesis, it is expected that the pathophysiology of mood disorder and
      clinical mechanism of mood stabilizers and antidepressants can now be understood
      as an integrated story.

PMID- 25069264
TI  - [Haplotype analysis of serotonin 2A receptor gene polymorphisms and smoking
      behavior].
AB  - In this study, the relationship between the haplotypes consisting of single
      nucleotide polymorphisms (SNPs) of serotonin 2A receptor (5HT2AR) gene (HTR2A)
      102T/C (rs6313) and -1438A/G (rs6311) and smoking behavior was studied among 101
      smokers and 99 non-smokers. It was shown that the genotypic and allelic
      frequencies of these polymorphisms were not associated with the smoking behavior.
      However, according to haplotype analysis, higher haplotype 1 ((-1438G) G-(102)T)
      frequency was observed in smokers than in non-smokers (P < 0.05). Pairwise D' and
      gamma2 values between the two SNPs in this study were 0.916 and 0.805,
      respectively. The two SNPs thus showed strong linkage disequilibrium with each
      other. This study suggests that 5-HT2AR gene haplotype (G-T) may be related to
      smoking behavior.

PMID- 25069266
TI  - [Role of apolipoprotein E in the molecular pathomechanism of Alzheimer disease].
AB  - Apolipoprotein E (Apo-E) is a major cholesterol carrier regulating lipid
      transport and injury repair in the brain. It is known that individuals carrying
      the epsilon4 allele are at increased risk of Alzheimer disease (AD) compared with
      those carrying the more common epsilon3 allele, whereas the epsilon2 allele
      decreases risk. ApoE-HDL binds to several cell-surface receptors to deliver
      lipids, and also to amyloid-beta (Abeta) proteins. Abeta is thought to initiate
      toxic events that lead to synaptic dysfunction and neurodegeneration in AD. It
      has been shown that Apo-E isoforms differentially regulate Abeta aggregation and
      clearance in the brain, and have distinct functions in regulating brain lipid
      transport, and mitochondrial function. In this review, we summarize current
      knowledge about Apo-E in the CNS, with a particular emphasis on its functions to
      generate HDL and clear/degradate of HDL-bound Abeta with different ApoE isoforms.

PMID- 25069265
TI  - [Synapse maturation and autism: learning from neuroligin model mice].
AB  - Autism is a neurodevelopmental disorder characterized by impairments in social
      interaction, communication, and restricted and repetitive behavior. Synaptic
      defects have been implicated in autism; nevertheless, the cause is still largely
      unknown. A mutation that substitutes cysteine for arginine at residue 451 of
      Neuroligin-3 (R451C) is the first monogenic mutation identified in idiopathic
      autism patients. To study the relationship between this mutation and autism, we
      generated knock-in mice that recapitulated this mutation. The knock-in mice were
      born and grew up normally without showing any major physical phenotypes, but
      showed a deficit in social interaction. We studied synaptic function in the layer
      II/III pyramidal neurons in the somatosensory cortex and found inhibitory
      synaptic transmission was enhanced in the knock-in mice. The administration of
      GABA blocker rescued social interaction, suggesting that this caused autistic
      behavior in these mice. We also found, by Morris water maze test, that spatial
      learning and memory were significantly enhanced in the knock-in mice.
      Electrophysiology in the CA1 region of the hippocampus revealed that LTP, the
      NMDA/AMPA ratio, and NR2B function were enhanced, indicating that synaptic
      maturation was impaired in the knock-in mice. This may cause the deficit in
      social behavior and extraordinary memory ability occasionally seen in autistic
      patients.

PMID- 25069268
TI  - [Appeal of Russian Federation Health Minister V.I. Skvortsova to participants of
      XII Russian Congress "Occupation and Health" and of V Russian Congress of
      Occupational therapists].

PMID- 25069267
TI  - [Microglial hypothesis of schizophrenia].
AB  - While the etiology of schizophrenia remains unclear, there has been a growing
      amount of evidence pointing to neuroinflammation, which is characterized by an
      increased serum concentration of several pro-inflammatory cytokines and an
      increase of microglia in the brain of schizophrenics. Microglia respond rapidly
      to even minor pathological changes in the brain and may contribute directly to
      neuronal degeneration by producing various pro-inflammatory cytokines and free
      radicals. In many aspects, the neuropathology of schizophrenia has recently been
      reported to be closely associated with microglial activation. Our "Microglia
      Hypothesis of Schizophrenia" may shed a new light on the therapeutic strategy for
      schizophrenia.

PMID- 25069269
TI  - [Appeal of XII Russian Congress "Occupation and Health" President N.F. Izmerov,
      honoured scientist, member of RASc, to participants of XII Russian Congress
      "Occupation and Health"].

PMID- 25069270
TI  - [Resolution of XII Russian Congress "Occupation and Health" and V Russian
      Congress of Occupational therapists, Moscow, November 27-30, 2013].

PMID- 25069271
TI  - [Forecasting decrease in performance and health disorders under exposure to work
      intensity factors in accordance with work conditions class].
AB  - Results of complex physiologic and ergonomic, clinical and functional studies
      helped to justify approaches to quantitative evaluation and assessment of
      posssible decrease in performance and health disorders in workers in accordance
      with work conditions class of mental work. Linear regression dependence was
      established between work intensity class and performance decrease. The linear
      regression equation obtained enables to calculate a percentage of performance
      decrease in various work intensity classes. Intensive direct correlation was
      revealed between work intensity value and a percentage of individuals with
      diagnosed occupationally induced diseases.

PMID- 25069272
TI  - [Influence of work factors on health state in personnel servicing military
      nuclear technical objects].
AB  - Complex of occupational studies and medical, statistical research helped to
      reveal climate, geographic and other factors influencing health state of
      personnel servicing military nuclear technical objects. Considering peculiarities
      of occupational activities in various specialists, the authors specified measures
      to improve medical service for nuclear technical military officers directly
      working with nuclear ammunition. Practical application of the measures helped to
      gain 1.5-1.7 times improvement in morbidity parameters among nuclear technical
      military officers.

PMID- 25069273
TI  - [Epidemiologic situation in Ukraine, concerning malignant mesothelioma
      prevalence].
AB  - Malignant mesothelioma is an "indicator" tumor for evaluating public exposure to
      asbestos (mostly amphibolitic). Over 2001-2011 in Ukraine a total of 2645 cases
      of malignant mesothelioma was registered (annual number is 240.5 +/- 29.0 cases).
      1 case of malignant mesothelioma per 457.4 tons of asbestos consumed by industry.
      Median annual levels of malignant mesothelioma morbidity in Ukraine (world
      standard): males--0.60; females--0.31 per 100,000 of general population. These
      levels are lower than worldwide (males--1.11; females--0.30) and Europaen WHO
      ones (males--1.53; female--0.37). Medians of malignant mesothelioma morbidity age
      are not different between males and females in Ukraine (males 59.5 +/- 13.2
      years; females 62.6 +/- 13.1 years; p > 0.05). Most frequent location of
      malignant mesothelioma is on pleura (males 95.3%; females 89.8%). Now Ukraine is
      among the countries with low level (< 0.8 per 100,000 general population) and
      moderate (19.0-0.1% per year) increase of malignant mesothelioma morbidity in
      European WHO region. Up to 2025, the prognosis is of increased malignant
      mesothelioma morbidity in Ukraine to 0.97 [0.70-1.18] per 100,000 general
      population, and in European WHO region--to 2.68. Over 1992-2011, in Ukraine 3
      cases of occupational malignant mesothelioma were diagnosed (2 cases of them were
      connected with occupational exposure to asbestos dust).

PMID- 25069274
TI  - [Hygienic evaluation of air pollution with asbestos dust in subway parkings].
AB  - Hygienic research and analysis of literature on subway parkings air pollution
      with respirable fibrous particles that are formed during automobile exploitation
      due to attrition of friction parts (brake blocks, clutch plates) helped to come
      to a conclusion that level of air pollution with fibrous particles does not
      exceed allowable hygienic norms and accordingly does not harm health of workers
      and visitors of subway parkings, therefore there is no need in improvement of
      present hygienic regulations of such objects in view of preventing asbestos
      induced diseases.

PMID- 25069275
TI  - [Problems of androgen deficiency associated with somatic diseases in vibration
      disease patients].
AB  - The article deals with new scientific data on influence of industrial vibration
      on prevalence of androgen deficiency in vibration disease pateints, correlation
      between androgen deficiency level and general somatic diseases in vibration
      disease patients, criteria of early diagnosis of the combined pathology.

PMID- 25069276
TI  - [Role of children physical development in radiation hygienic monitoring system].
AB  - The article deals with longstanding work on studies of physical development
      parameters among preschoolers aged 4-7 and dwelling on territories near to
      objects with potential radiation danger, also on radiation-connected anxiety in
      parents of the examined children. The stated objects when exploited in normal
      mode were proved to cause no influence on the children's development. Social and
      economical factors appeared to play leading role in developmental parameters
      formation. Increased level of radiation-connected anxiety in parents of the
      children examined appeared to be out of proportion to real favorable radiation
      background of the territories examined.

PMID- 25069277
TI  - [Information as physical factor: problems of measurement, hygienic assessment and
      IT-automation].
AB  - The increasing flow of information, speeding up the progress of society, can
      impact the health that puts the task of its hygienic reglamentation. The physical
      aspects of information, parameters and units of quantities, aspects of
      measurement and evaluation with account of information quantity and quality as
      well as criteria of its permissible and optimal levels are considered. The
      results of measurements of quantity of text information produced per year on
      computer in 17 occupations of 10 economic sectors are presented. The principle of
      IT-automation of operator's work and of dynamic monitoring is proposed. On the
      basis of research performed the glossary of terms and guide on the problem with
      computer support are elaborated for the accumulation of experience and
      clarification of prospects.

PMID- 25069278
TI  - [The peculiarities of the influenza epidemics in some areas of Russia during 2012
      2013 season. The influenza A (H1N1) pdm09 virus domination in European
      countries].
AB  - The peculiarities of the influenza viruses circulation in 2012-2013 are
      discussed. The results were obtained in 10 cities of Russia, where basic
      laboratories of the Influenza Ecology and Epidemics Center of on the basis of
      Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation,
      are situated. The increasing rate of the ARD morbidity caused by influenza
      viruses was observed in January-March 2013. The highest indices of the morbidity
      were detected during 6-7 weeks with the following decreasing rate till threshold
      levels to week 14. The influenza A (H1N1) pdm09, A (H3N2), and B viruses were the
      cause of the epidemic, but their activity differed over areas of Russia. The
      results of study of the antigenic and genetic properties of the influenza strains
      demonstrated closed relatives with respect to vaccine strains. In addition, some
      heterogeneity of the circulating strains and their drift variants were found as
      well. All tested strains were sensitive to oseltamivir (excluding one A (H1N1)
      pdm09 strain), zanamivir, arbidol, and remained resistant to rimantadine. The
      ratio of the ARD viruses was comparable with the last epidemic seasons.

PMID- 25069279
TI  - [Vaccine-like viruses: peculiarities of circulation in the South America].
AB  - The peculiarities of the spread of vaccine-like viruses first revealed more than
      50 years ago in the area of the South America was discussed. These viruses cause
      infective episodes among milk cattle and caretaking personnel. Cancellation of
      the smallpox vaccination in 1980 resulted in a decrease in the community immunity
      and increased the risks of human infection. This circumstance makes it necessary
      to activate monitoring of the properties of the vaccine-like viruses, the circle
      of hosts and possible changes in the pathogenicity for humans.

PMID- 25069280
TI  - [Taxonomy of previously unclassified Tamdy virus (TAMV) (Bunyaviridae,
      Nairovirus) isolated from the Hyalomma asiaticum asiaticum Schulce et Schlottke,
      1929 (Ixodidae, Hyalomminae) in the Middle East and transcaucasia].
AB  - Complete genome sequencing of three Tamdy (TAMV) virus strains was carried out.
      The prototype strain TAMV/LEIV-1308Uz was isolated for the very first time from
      the Hyalomma asiaticum asiaticum Schulce et Schlottke, 1929 (Ixodidae,
      Hyalomminae) collected in the August 1971 from sheep in the arid area near
      Namdybulak town (41 degrees 36' N, 64 degrees 39' E) in the Tamdinsky district of
      the Bukhara region (Uzbekistan). TAMV was revealed to be a prototype member of
      the new phylogenetic group within the limits of the Nairovirus. The TAMV homology
      for RdRp (L-segment) amino acid sequence is not less than 40% with Crimea-Congo
      hemorrhagic fever virus (CCHFV), Hazara virus (HAZV), and Dugbe virus (DUGV),
      which are also linked with Ixodidae ticks. The TAMV homologies with the Issyk-Kul
      virus (ISKV) and Caspiy virus (CASV) for RdRp are 37.6% and 37.7%, respectively.
      These data conformed to the low values of GnGc (M-segment) and nucleocapsid
      protein N (S-segment) homology. The TAMV homologies with the nairoviruses for
      GnGc is in average 25%; with the nairoviruses linked with Ixodidae ticks (CCHFV,
      DUGV, HAZV) - 33%; with Argasidae ticks (ISKV, CASV) - 28%. The TAMV/LEIV-1308Uz,
      LEIV-6158Ar, and LEIV-10226Az have high level of identity. The TAMV/LEIV-10226Az
      from Azerbaijan has 99% homology for both nucleotide and amino acid sequences of
      the prototype TAMV/LEIV-1308Uz RdRp. The TAMV/LEIV-6158Ar from Armenia is more
      divergent and has 94.2% and 96.3% homologies with the TAMV/LEIV-1308Uz,
      respectively. The homology between the TAMV/LEIV-1308Uz and TAMV/LEIV-10226Az for
      GnGc is 93%. The TAMV/LEIV-6158Ar has 90% homology for this protein with the
      TAMV/LEIV-1308Uz and 93% with the TAMV/LEIV-10226Az, respectively. Differences in
      nucleocapsid protein between three TAMV strains are 5-7%.

PMID- 25069281
TI  - [Molecular-genetic characterization of the Okhotskiy virus (OKHV) and Aniva virus
      (ANIV) (Orbivirus, Reoviridae) isolated from the ticks Ixodes (Ceratixodes) uriae
      White, 1852 in high latitudes of the Northern Eurasia].
AB  - Molecular-genetic characteristics of the Okhotskiy virus (OKHV) and Aniva virus
      (ANIV) were studied (ID GenBank KF981623-32). These viruses are distributed over
      the shelf and Island areas in the high latitudes in the Okhotsk, Bering, and
      Barents seas and linked with nesting colonies of Alcidae seabirds and their
      obligatory parasites, the Ixodes uriae (Ixodidae) ticks. OKHV and ANIV are
      observed to be independent species within the limits of the Great Island virus
      (GIV) group of the Orbivirus genus of the Reoviridae family. The majority of the
      genes of OKHV and ANIV have high homology (VP1 - 96%, T2 - 99%, VP7 (T13) - 98%,
      NS1 - 94%, NS2 - 98%, NS3 - 72%, VP6 - 93%). Nevertheless, the envelope proteins
      containing the main specific antigenic determinants (VP2 and VP5) of OKHV and
      ANIV are sufficiently different (62% and 68% homology for amino acid sequences,
      respectively).

PMID- 25069282
TI  - [Taxonomic status of the Tyulek virus (TLKV) (Orthomyxoviridae, Quaranjavirus,
      Quaranfil group) isolated from the ticks Argas vulgaris Filippova, 1961
      (Argasidae) from the birds burrow nest biotopes in the Kyrgyzstan].
AB  - The Tyulek virus (TLKV) was isolated from the ticks Argas vulgaris Filippova,
      1961 (Argasidae), collected from the burrow biotopes in multispecies birds colony
      in the Aksu river floodplain near Tyulek village (northern part of Chu Valley,
      Kyrgyzstan). Recently, the TLKV was assigned to the Quaranfil group (including
      the Quaranfil virus (QRFV), Johnston Atoll virus (JAV), Lake Chad virus) that is
      a novel genus of the Quaranjavirus in the Orthomyxoviridae family. In his work,
      the complete genome (ID GenBank KJ438647-8) sequence of the TLKV was determined
      using next-generation sequencing (Illumina platform). Comparison of deduced amino
      acid sequences shows closed relationship of the TLKV with QRFV and JAV (86% and
      84% identity for PB1 and about 70% for PB2 and PA, respectively). The identity
      level of the TLKV and QRFV in outer glycoprotein GP is 72% and 80% for nucleotide
      and amino acid sequences, respectively. The phylogenetic analysis showed that the
      TLKV belongs to the genus of the Quaranjavirus in the family Orthomyxoviridae.

PMID- 25069283
TI  - [Genetic characterization of the Batken virus (BKNV) (Orthomyxoviridae,
      Thogotovirus) isolated from the Ixodidae ticks Hyalomma marginatum Koch, 1844 and
      the mosquitoes Aedes caspius Pallas, 1771, as well as the Culex hortensis
      Ficalbi, 1889 in the Central Asia].
AB  - The prototype strain LEIV-K306 of the Batken virus (BKNV) was isolated from the
      Ixodidae ticks Hyalomma marginatum Koch, 1844 collected from sheep near town
      Batken (Kirgizstan) in the April 1970. Later, the BKNV was isolated in Kirgizstan
      from the mixed pool of the Aedes caspius Pallas, 1771 and Culex hortensis
      Ficalbi, 1889 mosquitoes. From the very beginning, the BKNV was discussed to be
      very close to the Dhori virus (DHOV) (Orthomyxoviridae, Thogotovirus) isolated
      from the Ixodidae ticks Hyalomma dromedarii Koch, 1844 in India. In this work,
      virtually complete genome sequence (MiSeq, Illumina) of the BKNV was determined
      (ID GenBank KJ396672-4). Structural and non-structural proteins of the BKNV have
      a high level of homology with DHOV - 98% (PB1) and 96% (PB2, PA, NP, M). Homology
      of HA protein between the BKNV and DHOV is 90%, which accounts for antigenic
      difference between these close relative viruses. Since the differences in the
      other structural and non-structural proteins are about 96-98%, the BKNV could be
      suggested as the topotypic DHOV strain for Central Asia, Transcaucasia, and
      Northern Caspian region. The evolution divergence of the BKNV and DHOV for HA
      could be explained by local ecologic peculiarities of the BKNV areal.

PMID- 25069284
TI  - [The antiviral activity of the adamantane derivatives against the influenza virus
      A (H1N1) pdm2009 model in vivo].
AB  - For the first time in vivo, the model of the viral pneumonia in mice was used to
      study the antiviral activity against influenza A virus (H1N1) pdm09 synthetic
      derivatives of adamantane series including the amino acid residues and lipoid
      acid. It was found that the adamantane derivatives with histidine, serine, and
      lipoid acid could inhibit the rimantadine-resistant strain of the influenza A
      (H1N1) pdm09. As a result, the lifespan of the mice infected with the virus has
      increased by 1.6 times with respect to viral control. Thus, the possibility of
      restoration of antiviral properties of rimantadine both in vitro and in vivo by
      introducing into its molecular structure new functionally active groups was
      tested.

PMID- 25069285
TI  - [Comparative study of MDCK and CaCo-2 cell lines for influenza virus isolation].
AB  - Study of effectiveness of CaCo-2 cell line for influenza virus isolation was
      carried out. It was shown that the properties of this cell line strongly depended
      on the source of its origin and cultivation conditions. The infectious activity
      of the influenza viruses on CaCo-2 cell line was virtually the same as in the
      MDCK cell line. The rate of the viral isolation was virtually identical for both
      cell lines tested, but viruses from post-mortem materials were isolated only in
      CaCo-2 cell line. In general, the CaCo-2 line is believed to be a valuable cell
      line for virological research, particularly for influenza virus isolation.

PMID- 25069287
TI  - Severe malnutrition: building on the past for a brighter future.

PMID- 25069286
TI  - [A study of the antiherpetic activity of the chaga mushroom (Inonotus obliquus)
      extracts in the Vero cells infected with the herpes simplex virus].
AB  - The chaga mushroom (Inonotus obliquus) contains a wide range of excellent
      bioactive compounds. However, limited information exists on the antiviral
      activity of the compounds extracted from chaga. A number of subfractions of chaga
      were obtained using different solvents and different procedures. The subfractions
      of chaga extracted with water, alcohol, alkali were tested for their toxicity for
      the Vero cell culture and antiviral effect in the Vero cells infected with the
      Herpes simplex virus (HSV), Type 1. It was shown that most of the subfractions
      were not toxic for the Vero cells and had protective effect on the Vero cells
      infected with HSV. The subfraction IV in the concentration 5 microg/ml protected
      the Vero cells from cytodestructive action of HSV and no viral DNA was detected
      in infected cells treated with chaga extracts. Best protective effect was
      observed when compound was added before or within one hour after the Vero cells
      were infected with HSV.

PMID- 25069288
TI  - Perspectives on the SUN Movement: Waterlow lecture delivered at the International
      Congress of Nutrition in Granada, 16 September 2013.
AB  - The Waterlow lecture was named to commemorate Professor John Waterlow, an eminent
      figure in nutrition during the last half of the 20th century. David Nabarro
      worked with Professor Waterlow for a period of his career and was invited to
      deliver the Waterlow lecture during the International Congress of Nutrition in
      Granada on 16 September 2013.

PMID- 25069290
TI  - Scaling up a community-based program for maternal and child nutrition in
      Thailand.
AB  - The first national nutrition survey of Thailand in 1960 revealed that
      malnutrition among children and women in this rice-exporting country was highly
      prevalent. Malnutrition received national-level attention in the 1970s, when a
      national multisectoral nutrition plan was included in the Fourth National
      Economic and Social Development Plan (NESDP) (1977-81), followed by effective
      implementation through Thailand's primary healthcare system and poverty
      alleviation plan in the 1982-87 NESDP. Nutrition was embedded into primary
      healthcare, and a community-based nutrition program was successfully implemented
      through community participation via manpower mobilization and capacity-building,
      financing, and organization. Growth-monitoring, promotion of infant and young
      child feeding, and joint financing (government and community) of a nutrition fund
      were implemented. The poverty alleviation plan made it possible to streamline
      resource allocations at the national level down to priority poverty areas, which
      also facilitated microlevel planning. Effective, integrated actions were
      undertaken using the basic minimum needs approach, wherein community people
      identified problems and participated in actions with inputs from government
      personnel. This effective process took about 5 years to put in place. In
      response, child undernutrition declined significantly. Severe malnutrition was
      practically eradicated, and it remains resilient despite social and economic
      challenges, such as the Asian economic crisis in 1977. Currently, stunting and
      subclinical micronutrient deficiencies remain, while overweight and obesity among
      children are rising rapidly. A different paradigm and strategy will be essential
      to address the nation's current nutrition challenges.

PMID- 25069289
TI  - Severe acute malnutrition in Asia.
AB  - Severe acute malnutrition (SAM) is a common condition that kills children and
      intellectually maims those who survive. Close to 20 million children under the
      age of 5 years suffer from SAM globally, and about 1 million of them die each
      year. Much of this burden takes place in Asia. Six countries in Asia together
      have more than 12 million children suffering from SAM: 0.6 million in
      Afghanistan, 0.6 million in Bangladesh, 8.0 million in India, 1.2 million in
      Indonesia, 1.4 million in Pakistan, and 0.6 million in Yemen. This article is
      based on a review of SAM burden and intervention programs in Asian countries
      where, despite the huge numbers of children suffering from the condition, the
      coverage of interventions is either absent on a national scale or poor. Countries
      in Asia have to recognize SAM as a major problem and mobilize internal resources
      for its management. Screening of children in the community for SAM and
      appropriate referral and back referral require good health systems. Improving
      grassroots services will not only contribute to improving management of SAM, it
      will also improve infant and young child feeding and nutrition in general. Ready
      to-use therapeutic food (RUTF), the key to home management of SAM without
      complications, is still not endorsed by many countries because of its
      unavailability in the countries and its cost. It should preferably be produced
      locally from locally available food ingredients. Countries in Asia that do not
      have the capacity to produce RUTF from locally available food ingredients can
      benefit from other countries in the region that can produce it. Health facilities
      in all high-burden countries should be staffed and equipped to treat children
      with SAM. A continuous cascade of training of health staff on management of SAM
      can offset the damage that results from staff attrition or transfers. The basic
      nutrition interventions, which include breastfeeding, appropriate complementary
      feeding, micronutrient supplementation, and management of acute malnutrition,
      should be scaled up in Asian countries that are plagued with the burden of
      malnutrition.

PMID- 25069291
TI  - Community-based management of acute malnutrition (CMAM) in sub-Saharan Africa:
      case studies from Ghana, Malawi, and Zambia.
AB  - BACKGROUND: Recent success with community-based management of acute malnutrition
      (CMAM) has spurred interest on how to improve coverage while maintaining
      treatment outcomes. OBJECTIVE: To document, as case studies, the experience of
      three African countries, Malawi, Ghana, and Zambia, in scaling up CMAM. METHODS:
      Desk review using published and unpublished data and country programmatic data
      and key informant interviews. RESULTS: All three countries, with different
      motivations for startup, have successfully integrated CMAM into their essential
      health packages for children under 5 years of age, at least in their policy and
      strategic documents. Strong leadership by the ministries of health has been
      instrumental, complemented by key stakeholders and donor partners. Implementation
      is at variable stages, depending on when the program rolled out, with Malawi
      having achieved the most integration, followed by Ghana and Zambia. Using CMAM,
      the three countries have significantly extended service coverage and improved
      treatment outcomes, with cure rates ranging from 73% in Ghana to 90% in Malawi,
      while maintaining very low death rates: 1.7% in Malawi, 2% in Ghana, and 5% in
      Zambia. CONCLUSIONS: CMAM is a viable option to improve service coverage and
      outcomes in health systems where inpatient therapeutic care alone cannot suffice.

PMID- 25069292
TI  - Treatment and prevention of malnutrition in Latin America: focus on Chile and
      Bolivia.
AB  - Seven million children under 5 years of age died worldwide in 2011, and one-third
      had malnutrition. Latin America and Caribbean countries stand out for the notable
      improvement of their health and nutrition situation, particularly in pregnant
      women and young children. Nutrition-sensitive interventions such as promoting
      food security, women's empowerment, social safety nets, clean water, and
      sanitation, among others, are critical for success. In Bolivia, the program
      Desnutricion Cero (Malnutrition Zero) was able to reduce mortality from severe
      malnutrition after 5 years from 25% to less than 5%, based on widespread
      implementation of the World Health Organization 10-steps protocol for
      hospitalized care and the application of community management. The Economic
      Commission for Latin America estimated the cost of malnutrition for Costa Rica,
      El Salvador, Guatemala, Honduras, Nicaragua, Panama, and the Dominican Republic
      as US $6,658 million. Approximately 1 million children have dropped out of school
      because of malnutrition, and as a result, malnourished children have 2 years less
      schooling, which brings social and economic losses not only to those affected but
      to society at large. National and international nutrition and food programs
      developed over the past 50 years have been implemented as integral components of
      broader strategies of primary healthcare and education, oriented toward
      preventing deaths and improving the quality of life of low-socioeconomic-status
      groups. Treating hundreds or thousands of affected children will not solve the
      global public health problem of malnutrition. Access to adequate amounts of
      quality foods represents a basic human right and is a necessary precondition for
      health. In turn, good nutrition and health are prerequisites for human, social,
      and economic development.

PMID- 25069293
TI  - Severe acute malnutrition during emergencies: burden management, and gaps.
AB  - Natural and man-made disasters, including floods, droughts, earthquakes, and
      armed conflicts, create nutrition crises. Unfortunately, the frequency and
      severity of such disasters have been increasing since the beginning of the 20th
      century, and their contribution to the burden of acute malnutrition is increasing
      every year. However, their contribution to the burden of acute malnutrition is
      underrecognized due to the ways in which global statistics are built and causes
      of death are reported. Fortunately, the success of the current protocol for
      treatment of severe acute malnutrition (SAM) and the integrated approach to
      treatment has created a momentum allowing expanded coverage of treatment of SAM,
      especially in humanitarian emergency contexts. For this progress to be maintained
      and accelerated, changes in nutrition information systems at the national and
      global levels are needed, and the persisting barriers to the expansion and
      integration of treatment of SAM into routine health systems need to be removed.
      Emergency funding approaches and objectives have to include sustaining and
      amplifying the achievements of the short-term palliative interventions. Nutrition
      programs implemented in emergency contexts have the capacity to contribute to
      answering priority research questions, and this capacity should be more optimally
      utilized.

PMID- 25069294
TI  - Development and implementation of a locally produced ready-to-use therapeutic
      food (RUTF) in Vietnam.
AB  - BACKGROUND: In Vietnam, malnutrition remains a public health problem, even though
      much progress has been made in the last decades. The number of cases of severe
      acute malnutrition (SAM) is more than 200,000 per year. To accelerate the
      treatment of SAM, community-based treatment with ready-to-use-therapeutic foods
      (RUTFs) is preferred. However, a locally available and acceptable RUTF for the
      treatment of SAM was lacking. OBJECTIVE: In a joint effort by the National
      Institute of Nutrition, UNICEF, and the Institut de Recherche pour le
      Developpement, a local RUTF was developed and tested. METHODS: The product was
      optimalized for impact and acceptability. At the same time, capacity for the
      Integrated Management of Acute Malnutrition (IMAM) was developed. RESULTS: The
      local product was found to be highly acceptable and effective. After training of
      health staff the product could be introduced in the IMAM program. CONCLUSIONS:
      The IMAM program was highly successful in treating children with SAM, with more
      than 90% of the children recovering. Production capacity of the factory is
      currently being increased to enable up-scaling of the IMAM program and potential
      export of the product to countries in the region.

PMID- 25069295
TI  - Application of Hazard Analysis Critical Control Point in the local manufacture of
      ready-to-use therapeutic foods (RUTFs).
AB  - The local manufacture of ready-to-use therapeutic foods (RUTFs) is increasing,
      and there is a need to develop methods to ensure their safe production. We
      propose the application of Hazard Analysis Critical Control Point (HACCP)
      principles to achieve this goal. The basic principles of HACCP in the production
      of RUTFs are outlined. It is concluded that the implementation of an HACCP system
      in the manufacture of RUTFs is not only feasible but also attainable. The
      introduction of good manufacturing practices, coupled with an effective HACCP
      system, will ensure that RUTFs are produced in a cost-effective, safe, and
      hygienic manner.

PMID- 25069297
TI  - Fluid management of shock in severe malnutrition: what is the evidence for
      current guidelines and what lessons have been learned from clinical studies and
      trials in other pediatric populations?
AB  - Management of shock in children with severe malnutrition remains controversial.
      To date, the evidence supporting either benefit or harm of fluid resuscitation or
      rehydration is weak. This issue, however, is not unique to children with severe
      malnutrition; pediatric guidelines worldwide have a weak level of evidence and
      remain unsupported by appropriate clinical studies. In this review we give an
      overview of the current recommendations in other pediatric populations and
      appraise the strength of evidence supporting these. We summarize results from the
      only controlled trial ever undertaken, FEAST (Fluid Expansion As Supportive
      Therapy), which was conducted in resource-poor hospitals involving 3,141 African
      children with severe febrile illnesses and shock, including large subgroups with
      sepsis and malaria but excluding children with severe malnutrition. This high
      quality trial provided robust evidence that fluid resuscitation increased the
      risk of death, leading to an excess mortality of 3 in every 100 children
      receiving fluid boluses, compared with controls receiving no boluses. These
      findings may have particular relevance to management of septic shock in children
      with severe malnutrition. However, they cannot be extrapolated to children with
      gastroenteritis, since this condition was not included in the trial. Current
      observational studies under way in East Africa may provide insights into
      myocardial and hemodynamic function in severe malnutrition, including responses
      to fluid challenge in those complicated by gastroenteritis. Such studies are an
      essential step for setting the research agenda regarding fluid management of
      shock in severe malnutrition.

PMID- 25069296
TI  - Childhood malnutrition: toward an understanding of infections, inflammation, and
      antimicrobials.
AB  - BACKGROUND: Undernutrition in childhood is estimated to cause 3.1 million child
      deaths annually through a potentiating effect on common infectious diseases, such
      as pneumonia and diarrhea. In turn, overt and subclinical infections, and
      inflammation, especially in the gut, alter nutrient intake, absorption,
      secretion, diversion, catabolism, and expenditure. OBJECTIVE: A narrative
      overview of the current understanding of infections, inflammation, and
      antimicrobials in relation to childhood malnutrition. METHODS: Searches for
      pivotal papers were conducted using PUBMED 1966-January 2013; hand searches of
      the references of retrieved literature; discussions with experts; and personal
      experience from the field. RESULTS: Although the epidemiological evidence for
      increased susceptibility to life-threatening infections associated with
      malnutrition is strong, we are only just beginning to understand some of the
      mechanisms involved. Nutritional status and growth are strongly influenced by
      environmental enteric dysfunction (EED), which is common among children in
      developing countries, and by alterations in the gut microbiome. As yet, there are
      no proven interventions against EED. Antibiotics have long been used as growth
      promoters in animals. Trials of antibiotics have shown striking efficacy on
      mortality and on growth in children with uncomplicated severe acute malnutrition
      (SAM) or HIV infection. Antibiotics act directly by preventing infections and may
      act indirectly by reducing subclinical infections and inflammation. We describe
      an ongoing multicenter, randomized, placebo-controlled trial of daily
      cotrimoxazole prophylaxis to prevent death in children recovering from
      complicated SAM. Secondary outcomes include growth, frequency and etiology of
      infections, immune activation and function, the gut microbiome, and antimicrobial
      resistance. The trial is expected to be reported in mid-2014. CONCLUSIONS: As
      well as improving nutritional intake, new case management strategies need to
      address infection, inflammation, and microbiota and assess health outcomes rather
      than only anthropometry.

PMID- 25069298
TI  - Quality control issues related to assessment of body composition.
AB  - There are no internationally agreed quality standards for the measurement of
      stature, weight, and body composition. This lack of agreement constrains the
      quality of work in nutrition and must be addressed in order to build systemic
      capacity within the Scaling Up Nutrition agenda. There is a need to reach
      agreement and define standards of performance and the required training to be
      able to demonstrate the competency of those responsible for making the
      measurements. This, together with the adoption of standardized protocols,
      traceable reference materials, quality assurance frameworks, and publication
      guidance, would mark an important first step in improving the conduct and
      interpretation of measurements of growth and body composition.

PMID- 25069299
TI  - Information-sharing to improve learning about community-based management of acute
      malnutrition (CMAM) and its impact.
AB  - BACKGROUND: Severe acute malnutrition (SAM) affects 19 million children worldwide
      annually. The community-based management of acute malnutrition (CMAM) approach
      was first piloted in 2000. Endorsed by the United Nations in 2007, the approach
      has been introduced in over 60 countries. Current coverage and quality of
      services need further strengthening and key stakeholders have expressed the need
      for improved information-sharing. OBJECTIVE: To report on an information-sharing
      initiative that was established to support scale-up of quality services for CMAM
      by collecting existing technical guidance, evidence, and learning. METHODS:
      Routine website monitoring, country case studies, and surveys were used to assess
      the profiles of CMAM Forum users and the reach and use of information for
      improved health outcomes. RESULTS: The number of information products and
      services and their use have steadily increased. Country case studies have
      identified ways to adapt information better to the needs of those involved in
      managing acute malnutrition, particularly at the country level. An urgent need
      has been identified for more resources in additional languages, especially French
      and Arabic, and expanded production and use of audiovisual material and social
      media. CONCLUSIONS: Improved information-sharing can have an impact on health
      outcomes, but further innovation and support are needed to improve access to, and
      use of, the information.

PMID- 25069300
TI  - [Role of apolipoprotein AI on nascent high-density lipoprotein particle
      formation].
AB  - Apolipoprotein AI (apoA-I) is the major protein component of high-density
      lipoprotein (HDL), and apoA-I can stabilize the structure of HDL. Whereas the
      amphipathic alpha-helix is the structural motif for apoA-I to complete the
      corresponding functionality. In the lipid-free state, the N-terminal of apoA-I
      molecule is a dynamic four-helix bundle structure, most amino acid residues of
      the C-terminal domain is the formation of a disordered structure, which is the
      initial domain that mediates bingding to phospholipid surface. Two molecules of
      apoA-I are arranged in an anti-parallel, double-belt conformation around the
      surface of the discoidal HDL particles. However, the apoA-I molecule forms a
      trefoil scaffold structure, which can adapt to the surface of spherical HDL
      particles. ATP-binding cassette transporter A1 (ABCA1) can mediate phospholipid
      and cholesterol efflux from intracellular and interact with apoA-I to generate
      nascent HDL particles. Overall, apoA-I and HDL as an anti-atherosclerotic effect
      of primary target, we focus on the molecular structure of apoA-I, which
      determines the structure and function of different size of HDL particles, as well
      as the conformational changes after interaction with lipids, in order to learn
      more about the relationship of apolipoprotein and lipids metabolism against
      atherosclerosis.

PMID- 25069301
TI  - [Research advances in the effects of excise and diet on LPL and its mechanism].
AB  - Lipoprotein lipase (LPL) plays a major role in the metabolism and transport of
      lipids by hydrolyzing core triglycerides (TG) in chylomicrons and very low
      density lipoprotein. LPL is mainly synthesized and secreted by fat cells,
      myocardial cells and skeletal muscle cells. The expression and activity of LPL
      are regulated by multiple factors, such as hormones, nutrition, exercise,
      PPARgamma, apolipoproteins, glycosylphosphatidylinositol-anchored high-density
      lipoprotein-binding protein 1 (GPIHBP1) and angiopoietin-like proteins (ANGPTL).
      After introducing advance in LPL structure and regulation, we review the effects
      of exercise and diet intervention on the expression and activity of LPL and its
      possible mechanism.

PMID- 25069302
TI  - [The functions and clinical studies of macrophage migration inhibitory factor].
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic immunoregulator
      which has a unique structure and a chemokine-like function. Since it was
      dicovered in 1966, the functions of MIF have been indicated, such as non-specific
      immunity, the inflammatory cell recruitment, and inflammatory reaction. In
      addition to its eponymic activity, MIF also has a proinflammatory function and
      promotes the directed migration and recruitment of leukocytes into infectious and
      inflammatory sites; it also has functions such as anti-glucocorticoids, anti
      apoptosis , and promoting the release of other cytokines. As a result, MIF plays
      an important role in atherosclerosis, autoimmune diseases, cancer, and metabolic
      diseases. In this review, we will discuss the molecular pathway, function,
      related diseases and clinical application of MIF.

PMID- 25069303
TI  - [The biological function of osteocytes].
AB  - Osteocytes are the most abundant and longest-surviving cells in bone tissue.
      Through cell synapses, osteocytes keep in contact with each other and with other
      types of cells on bone matrix surface, constituting a dynamic and active cell
      regulation network in bone homeostasis. Osteocytes can directly sense mechanical
      stimulus, translate it into biochemical signals and send to other cells. In
      addition, osteocytes can mediate bone remodeling by secreting a variety of
      cytokines. In summary, it is indicated that osteocytes play a crucial role in
      skeletal mechanotransduction, and they also act as the major regulator
      responsible for skeletal metabolic balance and microenvironment homeostasis. The
      integrated network of osteocytes is essential to maintain the normal function of
      bone tissue.

PMID- 25069304
TI  - [Lipodystrophy and impairment of adipocyte differentiation].

PMID- 25069305
TI  - [Development of research on relationship between NLRP3 inflammasome and type 2
      diabetes].

PMID- 25069306
TI  - [A novel myokin:myonectin].

PMID- 25069307
TI  - [Betatrophin: a new bioactive peptide].

PMID- 25069308
TI  - [Role of mitochondrial dynamics in insulin resistance of type 2 diabetes].

PMID- 25069309
TI  - [Effects of chemokines on the occurrence and development of Alzheimer's disease].

PMID- 25069310
TI  - [The heterogeneity of dopaminergic neurons in ventral tegmental area].

PMID- 25069311
TI  - [The protective effect of uncoupling protein-2 on vascular endothelial cells].

PMID- 25069312
TI  - [The role of AGE and RAGE in diabetic neuropathy].

PMID- 25069313
TI  - [Neuroprotective effects of ghrelin in Parkinsons disease and Alzheimer's
      disease].

PMID- 25069314
TI  - [Research progress of correlation between tight junction protein claudin-7 and
      malignant tumors].

PMID- 25069315
TI  - [The biological function of stem cell antigen-1 and its role in diseases].

PMID- 25069316
TI  - [Correlation research between changes of breathing during sleep and AMS].

PMID- 25069317
TI  - [The crosstalking between alpha-synuclein and protein degradation pathways].

PMID- 25069318
TI  - [Recent advances in sample preparation methods of plant hormones].
AB  - Plant hormones are a group of naturally occurring trace substances which play a
      crucial role in controlling the plant development, growth and environment
      response. With the development of the chromatography and mass spectroscopy
      technique, chromatographic analytical method has become a widely used way for
      plant hormone analysis. Among the steps of chromatographic analysis, sample
      preparation is undoubtedly the most vital one. Thus, a highly selective and
      efficient sample preparation method is critical for accurate identification and
      quantification of phytohormones. For the three major kinds of plant hormones
      including acidic plant hormones & basic plant hormones, brassinosteroids and
      plant polypeptides, the sample preparation methods are reviewed in sequence
      especially the recently developed methods. The review includes novel methods,
      devices, extractive materials and derivative reagents for sample preparation of
      phytohormones analysis. Especially, some related works of our group are included.
      At last, the future developments in this field are also prospected.

PMID- 25069319
TI  - [Advances and applications of selective reaction monitoring technology in
      proteomics study ].
AB  - As an important technology for targeted protein analysis, selective reaction
      monitoring technology (SRM) improves the detection sensitivity and quantification
      accuracy by eliminating the interference of impurities and co-eluting peptides by
      selective detection of specific mother ions and daughter ions. It has been widely
      applied to the quantitative proteomics study due to the advantages of high
      selectivity, excellent reproducibility, high sensitivity and wide dynamic range
      and plays an important role in the area of life science. For the quantitative
      analysis of the complex samples with wide dynamic range, the throughput of
      analysis and detection sensitivity still need to be improved. Moreover, van
      quantification strategies have been proposed to improve the accuracy and
      precision of quantification. Furthermore, data processing becomes more and more
      important with the application of SRM technology to the analysis of complex
      samples. In this work, the recent development of SRM technology is reviewed from
      the above mentioned aspects. Since SRM technology gains wider applications along
      with the technological development, its applications in the area of proteomics
      quantitative study including biomarker validation, post-translational proteomics
      study (phosphorylation, glycosation, acetylation and so on), biotechnology and
      signaling pathway analysis are briefly described. Finally, the future
      developments, applications and outlook of SRM technology are described.

PMID- 25069320
TI  - [Recent advancement of photonic-crystal-based analytical chemistry].
AB  - Photonic crystals are a type of novel materials with ordered structure,
      nanopores/channels and optical band gap. They have hence important applications
      in physics, chemistry, biological science and engineering fields. This review
      summarizes the recent advancement of photonic crystals in analytical chemistry
      applications, with focus on sensing and separating fields happening in the
      nearest 5 years.

PMID- 25069321
TI  - [Development of online conventional array-based two-dimensional liquid
      chromatographic system for proteins separation in human plasma].
AB  - Human plasma is one of the proteins-containing samples most difficult to
      characterize on account of the wide dynamic concentration range of its intact
      proteins. Herein, we developed a high-throughput conventional array-based two
      dimensional liquid chromatographic system for proteins separation in human plasma
      in online mode. In the system, a conventional strong-anion exchange
      chromatographic column was used as the first separation dimension and eight
      parallel conventional reversed-phase liquid chromatographic columns were
      integrated as the second separation dimension. The fractions from the first
      dimension were sequentially transferred into the corresponding reversed-phase
      liquid chromatographic precolumns for retention and enrichment using a 10-port
      electrically actuated multi-position valve. The second dimensional solvent flow
      was directly and identically split into 8 channels. The fractions were
      concurrently back-flushed from the precolumns into the 8 conventional RP columns
      and were separated simultaneously. An 8-channel fraction collector was refitted
      to collect the reversed-phase liquid chromatographic fractions for further
      investigation. Bicinchoninic acid (BCA) dyein solution was conveniently used for
      high-abundance protein location. Two separation dimensions were relatively
      independent parts, as well as each channel of the second dimensional array
      separation. Therefore, the new system could improve the separation throughput and
      total peak capacity. The system was successfully applied for the separation of
      human plasma intact proteins. The results indicated the established system is an
      effective method for removing high abundance proteins in plasma and in-depth
      research in plasma proteomics.

PMID- 25069322
TI  - [A method using spectrum alignment to improve analysis efficiency of liquid
      chromatography combined with mass spectrometry].
AB  - In the analysis of proteins in human umbilical vein endothelial cells (HUVEC)
      treated with dimethyl sulfoxide (DMSO) and NEDD8-activating enzyme inhibitor
      (MLN4924, MLN), the Progenesis LC-MS software (Nonlinear Dynamics Ltd) was
      applied to liquid chromatography spectrum alignment, while spectrum similarities
      were figured out among several experiments of the same sample, and also among
      different samples. After double enzymolysis, the sample was added with digested
      QconCAT standard proteins. They were separated by HPLC-MS/MS, followed by
      spectrum alignment and data analysis. This established experiment flow offered a
      better identification result of more than 8 000 proteins, while the original
      result was about 7 000 proteins, ensuring a relatively high identification
      efficiency. On the basis of relative quantification with spectrum count, the
      described procedure can analyze the differential expression of proteins induced
      by DMSO and MLN. The similarities of total ion chromatograms after alignment were
      also compared. This method was proved to be quick and easy, with the advantages
      of high throughput and high sensitivity.

PMID- 25069323
TI  - [Establishment and application of integrated platform for proteome
      quantification].
AB  - To improve the accuracy, throughput and automation of proteome quantification
      analysis, an integrated platform including a microflow mixed-bed ion exchange
      column, a hydrophilic immobilized enzymatic reactor (hIMER) and nanoRPLC
      electrospray ionization (ESI)-MS/MS system was established. Online separation and
      digestion of dimethylated proteins, followed by peptide separation,
      identification and quantification can be realized automat ically by this
      platform. High and light dimethyl-labeled (H/L) proteins with the mass ratio of
      1:1 were used to evaluate the quantification performance of the platform. The
      results showed that the dimethyl labeling efficiency at protein level was 90%.
      The incomplete digestion resulting from 10 min online digestion by the hIMER
      column and the non-specific adsorption of protein digests on the column had
      little adverse effect on the accuracy of protein quantification results. The mean
      value of H/L (mass ratio) of all the quantified proteins was 1.01. This platform
      was finally applied to analyze the different protein expression levels of two
      mice hepatocarcinoma ascites cell lines with high and low lymph node metastasis
      rates (Hca-F and Hca-P cell lines). Finally 15 up-regulated and 12 down-regulated
      proteins (Hca-F/Hca-P) were successfully obtained. All these results demonstrated
      that the integrated platform can be used for proteome quantification with the
      advantages of high accuracy and high throughput.

PMID- 25069324
TI  - [Metal-tag labeling coupled with high performance liquid chromatography-selected
      ion monitoring mass spectrometry for absolute quantitation of proteins].
AB  - A novel method has been established based on metal element chelated tags coupled
      with high performance liquid chromatography-selected ion monitoring mass
      spectrometry (HPLC-SIM/MS). The labeling efficiency and stability of metal
      element chelated tags, the chromatographic retention behavior and MS behavior of
      the labeled peptides, the linear range and accuracy of this method were examined.
      The results showed that the metal element chelated tag method has high labeling
      efficiency and high labeling stability, and the labeled peptides with different
      kinds of metal tags have consistent chromatographic retention behavior. The
      method of metal tags coupled with HPLC-SIM/MS has high sensitivity with the limit
      of quantification (LOQ) up to 1 fmol. The linear range for the method was between
      1 fmol to 500 fmol with R2 > 0.99, which means the method has a good linearity.
      Moreover, this method had an average recovery of 117.01%. The method was used in
      the absolute quantitation of a protein enolase in Thermoanaerobacter
      tengcongensis (TTE) with a relative standard deviation of 5.74%, which means high
      precision. All the results showed that this method is accurate and reliable for
      the absolute quantitation of proteins. This gives us an alternative for the
      quantitative determination of proteins in relatively simple biological samples.

PMID- 25069325
TI  - [Enrichment of glycoproteins in human serum using concanavalin A-functionalized
      magnetic nanoparticles and identification by mass spectrometry].
AB  - Biomedical sciences, and in particular biomarker research, demand efficient
      glycoprotein enrichment platforms. Herein novel magnetic nanoparticles with an
      average size around 135 nm in diameter were prepared for the enrichment of
      glycoproteins in human serum. The prepared magnetic nanoparticles possessed
      uniform core/shell/shell structure which was composed of 8 nm magnetite internal
      core and double layers consisting of silica and poly glycidyl methacrylate (GMA).
      The latter was constructed by seed polymerization. Modified by a polyethylene
      hydrophilic linker, it made the surfaces of the magnetic nanoparticles highly
      hydrophilic so as to reduce the nonspecific adsorption of proteins. We examined
      affinity purification of glycoprotein in diluted human serum using our prepared
      magnetic nanoparticles with immobilization of concanavalin A (MNP @ ConA). The
      enriched proteins were reduced, alkylated and digested with trypsin. These
      peptides then were separated by offline two-dimensional chromatography. Protein
      identification was realized with nano-high performance liquid chromatography
      orbitrap mass spectrometry. A total of 80 proteins were identified, among them 76
      proteins were found to be glycoproteins by use of bioinformatic tools. /3-2
      Glycoprotein 1 present in serum at low mass concentration around 0.000 01 g/L was
      also identified. This demonstrates the capability of magnetic nanoparticle for
      recovering minute amounts of glycoproteins from a fluid exhibiting a dynamic
      concentration range more than 12 orders of magnitude. Overall, MNP @ ConA has
      been proven to be an efficient alternative to currently available immobilization
      supports.

PMID- 25069326
TI  - [Effect of the lysine guanidination on proteomic analysis].
AB  - The guanidination of lysine side chain was paid great attention in recent years.
      It plays an important role in qualitative and quantitative proteomics. In this
      study, based on the results of separated peptides extracted from HeLa cells
      before and after the guanidination by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS), the effect of the guanidination of three different kinds
      of peptides was systematically analyzed. It was found that the selectivity of the
      guanidination of the lysine side chain was as high as 96.8%. The ratio of
      identified peptides with lysine at C-term to all peptides increased from 51.7% to
      57.3% and more new peptides were identified, while the ratio of peptides with
      lysine in the middle or without lysine changed little. Further study on the ratio
      of b and y ions indicated that there were more y ions of peptides with lysine at
      C-term after the guanidination. The results proved that the selective conversion
      of lysine to homoarginine by the guanidination could increase the sensitivity and
      selectivity of mass spectrum. The increased basicity and ability to sequester
      proton of lysine produced more y ions fragmentation information, which
      contributed to more identified peptides. It concluded that the lysine
      guanidination can improve the coverage of proteomic analysis.

PMID- 25069327
TI  - [Preparation and retention mechanism of a mixed-mode reversed-phase/weak-cationic
      exchange chromatographic packing].
AB  - A "mixed ligand" octyl-carboxylic co-bonded silica (OCS) packing was prepared by
      the method of "click chemistry". The resulting OCS packing was characterized by
      elemental analysis (EI) and Fourier transform infrared spectroscopy (FT-IR) to
      prove the successful immobilization of octyl and carboxylic groups on the surface
      of silica gel. Then the mixed-mode reversed-phase/weak-cationic-exchange (RP/WCX)
      retention mechanism of the OCS packing was quantitatively probed by studying the
      retention factors of a homologous series of three cationic surfactants on the
      mixed-mode stationary phase column as a function of the ammonium concentration in
      the eluent or the number of methylene groups in the solute. The one-site and two
      site mixed-mode retention models of the three cationic surfactants on the OCS
      phases were studied by investigating the logarithm and reciprocal relationships
      of retention factors and salt concentrations, demonstrating that the two-site
      model was more suitable for the description of individual RP or WCX contribution
      to total retention was obtained according to the mathematical equations of two
      site retention mechanism, which can provide some valuable guidance for the
      separation of real samples. This study developed the qualitative model of
      retention mechanism of the mixed-mode OCS packing, and a series of standard basic
      mixtures were well separated on the OCS packing, demonstrating the great
      application potential of OCS packing for the separation of various basic
      compounds.

PMID- 25069328
TI  - [Synthesis and chromatographic evaluation of sulfobetaine-based capillary
      zwitterionic hydrophilic monolithic column using a binary porogenic agent of
      polyethylene glycol/methanol].
AB  - Sulfobetaine-based capillary zwitterionic hydrophilic monolithic columns were
      synthesized with a novel binary porogenic agent of polyethylene glycol
      (PEG)/methanol. The polymer was prepared with (3-(metharyloylamino) propyl)
      dimethyl (3-sulfopropyl) ammonium hydroxide inner salt (SPP) as monomer,
      pentaerythritol triacrylate (PETA) as crosslinker, and azobisisobutyronitrile
      (AIBN) as initiator. In order to optimize the properties, the contents of the
      polymerization mixture were investigated. The optimum preparation conditions were
      as follows: the mass ratio of monomer and porogenator = 1:2.5; the mass ratio of
      SPP and PETA = 1:1 in the monomer; the mass ratio of PEG and methanol = 2:1 in
      the binary porogenic agent; the content of the initiator (AIBN) = 0.1% (m/m).
      With the binary porogenic agent of PEG/ methanol addition, good mechanical
      stability, homogeneous column bed, good permeability and narrow pore size
      distribution were obtained. In the capillary liquid chromatography mode, the
      hydrophilic monolith provided column efficiency up to 2.4 x 10(5) plates/m which
      was much higher than that fabricated by traditional method without PEG/methanol.
      The columns were used in capillary liquid chromatography and pressurized
      capillary electrochromatography for the separation of a mixture of phenols,
      nucleosides and so on.

PMID- 25069329
TI  - [Preliminary exploration of energy transfer about sample ionization process in
      electrospray ionization source].
AB  - Electrospray ionization source (ESI) can be used not only for the detection of
      small molecules, but also for large molecules such as proteins and peptides. This
      article proposes energy transfer theory based on the lowest energy principle by
      systematically analyzing ionization processes. The transference of the analyte
      from liquid phase to gas phase can be influenced by multiple forces during the
      ionization and vaporization processes, such as electrostatics force and van der
      Waals' force. The ionization of samples is the result of the interactions among
      multiple forces. During different stages of the ionization process, different
      forces lead to different effects. There are competition between evaporation and
      formation of multi-charge ions for charges. For molecules with different
      structures, Gibbs free energy between two phases from the changes of molecule
      shape or conformation may lead to ion evaporation, multiply charged macromolecule
      and chain ejection, etc. The energy transfer theory can simplify the three
      existing theories, as well as explain the solvent effect and electrolyte ion
      effect during ionization process. The proposed theory provides foundation to
      optimize the detection condition for different samples and to understand the real
      process of ionization.

PMID- 25069330
TI  - [Determination of nitrofuran residues in feed and water samples by monolith-based
      stir bar sorptive extraction and high performance liquid chromatography].
AB  - A simple, efficient and sensitive method for the simultaneous determination of
      nitrofurantoin (NFT), furazolidone (FZD) and nitrofurazone (NFZ) in feed and
      water samples was developed by stir bar sorptive extraction (SBSE) coupled to
      high performance liquid chromatography with diode array detection. The SBSE based
      on poly (vinylimidazole-divinylbenzene) (VIDB) monolithic material as coating was
      used to concentrate the three target analytes. To obtain the optimum extraction
      performance, several VIDB-SBSE parameters were investigated and studied,
      including pH value, ionic strength of sample matrix, extraction and desorption
      time. Under the optimized experimental conditions, the linear ranges were 0.5-200
      microg/L for FZD, 0.25-200 microg/L for NFT and NFZ. The limits of detection (S/N
      = 3) were in the range of 0.068-0.11 microg/L for the three analytes. The
      precision of the proposed method was evaluated in terms of intra- and inter-day
      repeatability calculated as RSD, and it was found that the RSDs were all below
      6%. The developed method was successfully applied to the determination of
      nitrofuran residues in animal feed and water samples. The satisfactory recoveries
      of the spiked target compounds were in the range of 80.6%-108%.

PMID- 25069331
TI  - [Monolith column solid-phase extraction coupled with high performance liquid
      chromatography in online mode for the determination of forchlorfenuron in
      fruits].
AB  - A novel method based on the monolithic column solid-phase extraction (SPE)
      coupled with high performance liquid chromatography in online mode was developed
      for the determination of trace forchlorfenuron in fruits. The enrichment factor
      of SPE for forchlorfenuron was 214. The method was fully validated. It showed a
      linear range of 0.01-50.00 microg/L and a limit of detection of 25 ng/L, with the
      relative standard deviation (RSD) of 3.9%. The proposed method was successfully
      applied for the determination of forchlorfenuron in grape, kiwifruit and
      watermelon samples, with the recoveries of 87.0%-120.7% and the RSDs of 0.6%
      9.2%. This online method was proved to be selective, sensitive and convenient for
      the determination of trace forchlorfenuron in complex samples.

PMID- 25069332
TI  - [Dispersive solid phase microextraction of vanillins in milk using magnetic
      nanoparticles of ferroferric oxide/carbon nanotubes combining with high
      performance liquid chromatography analysis].
AB  - Magnetic nanoparticles of ferroferric oxide/carbon nanotubes (Fe3O4/CNTs) were
      synthesized by chemically bonding single-walled carbon nanotubes (SWCNTs) to the
      Fe3O4 nanoparticles. The pretreated carboxyl SWCNTs were modified on the surface
      of amino-functioned Fe3O4 nanoparticles through the cross-linking reaction
      between 1-ethyl-3-( 3-dimethylaminopropyl) carbodiimide (EDC) and N
      hydroxysuccinimide (NHS). The synthesized Fe3O4/CNTs nanoparticles presented high
      super paramagnetic property and good dispersion ability, and were considered as
      good candidate adsorbents for dispersive solid phase microextraction. In this
      work, the synthesized FeO4/CNTs nanoparticles were applied to the extraction of
      vanillin additives, which was combined with high performance liquid
      chromatography (HPLC) analysis. The rapid and efficient preconcentration of
      vanillin and ethyl vanillin from different milk samples were successfully
      obtained with the detection limits of 10 microg/L and satisfactory recoveries of
      more than 92%. The results indicated that Fe3O4/CNTs magnetic nanoparticles were
      good pretreatment alternatives for the concentration of vanillin additives in
      milk products.

PMID- 25069333
TI  - Fast analysis of malachite green, leucomalachite green, crystal violet and
      leucocrystal violet in fish tissue based on a modified QuEChERS procedure.
AB  - Triphenylmethane dyes malachite green (MG) and crystal violet (CV) have been used
      as antimicrobial, antiparasitic and antiseptic agents in aquaculture. However, MG
      and CV, as well as their metabolites leucomalachite green (LMG) and leucocrystal
      violet (LCV) are potential mutagens and carcinogens. Thus, the efficient
      determination of dye residues is of great concern. Considering the complexity of
      the aquatic products, the sample pretreatment is significant for decreasing
      matrix interference and improving detection sensitivity. In this study, a simple
      and rapid QuEChERS procedure was developed and combined with HPLC analysis for
      the simultaneous determination of the four dyes in fish tissue. An XCharge C18
      column was applied in HPLC analysis to achieve good peak shape and selectivity.
      The pretreatment method involved the extraction of dyes from fish tissue and
      further clean-up with dispersive solid phase extraction (d-SPE) material. The
      extraction volume, extraction time as well as d-SPE materials were systematically
      optimized. The results indicated that reversed-phase/strong anion exchange
      (C18SAX) adsorbent in the d-SPE procedure could effectively improve the recovery
      compared with conventional C18 or C18 incorporated with primary secondary amine
      (PSA) material. Under optimized conditions, good linearity was achieved in the
      concentration range of 0.5-100 mg/L with R2 greater than 0. 998. The recoveries
      were 73%-91% and the precisions were 0.66%-5.41%. The results demonstrated the
      feasibility and efficiency of QuEChERS procedure incorporated with HPLC for dye
      monitoring.

PMID- 25069334
TI  - [Determination of n-octanol/water partition coefficients for persistent organic
      pollutants by reversed-phase high performance liquid chromatography with dual
      point retention time correction].
AB  - n-Octanol/water partition coefficients (logKow) for persistent organic pollutants
      (POPs) including polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzo
      p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and
      decabromodiphenylethane (DBDPE) have been determined by a modified method of
      reversed-phase high performance liquid chromatography (RP-HPLC). A dual-point
      retention time correction (DP-RTC) was used to rectify chromatographic retention
      time (tR) shift resulted from stationary phase aging and so on. Based on this
      correction, the relationship model between logKow and logk(w), the logarithm of
      the retention factor extrapolated to pure water, was trained by a set of model
      compounds (a total of 37) with reliable experimental logKow as training set,
      including benzene homologues, PAHs and PCDD/Fs-related compounds. A linear
      regression equation of logKow = (1.18 +/- 0.02) logk(w) + (0.36 +/- 0.11) was
      established with correlation coefficient (R2) of 0.985, cross-validated
      correlation coefficient (R2cv) of 0.983 and standard deviation (SD) of 0.16. This
      quantitative structure retention relationship (QSRR) model was further validated
      using four verification compounds, biphenyl, fluorene, PCDD 1 and PCDF 114, with
      reliable experimental logKow val- ues. The RP-HPLC-determined Kow values showed
      good consistency with shake-flask (SFM) or slow-stirring (SSM) results,
      especially for highly hydrophobic compounds. Then, the logKow values for 29 POPs
      of wide interest were evaluated by the improved RP-HPLC method for the first
      time. The DP-RTC-HPLC method is recommended for the determination of the logKow
      values of POPs with strong hydrophobicity.

PMID- 25069335
TI  - [Determination of N-nitrosodimethylamine in beer by frozen zone melting liquid
      liquid extraction/gas chromatography].
AB  - A simple and effective sample enrichment method of frozen zone melting liquid
      liquid extraction was optimized and validated for the analysis of trace N
      nitrosodimethylamine (NDMA) in beer samples. The method was based on high
      pressure liquid-liquid extraction with a low temperature frozen step. The 90 mL
      beer was placed in a container with 10 mL dichloromethane. After agitation, the
      sample was kept in a freezer for 16 h at -19 degrees C. The organic extract was
      analyzed by gas chromatography with a flame ionization detector (GC-FID). The
      accuracy, precision, detection and quantification limits and linearity of the
      method were evaluated. The results showed that the calibration curve of NDMA was
      linear in the range of 5-200 mg/L with a good correlation coefficient (r2) of
      0.999 6. The recoveries at the spiked levels of 5, 10 and 20 mg/L were 84.94%,
      83.24%, 85.14% with the relative standard deviations (n = 7) of 3.06%, 3.19%,
      2.63%, respectively. The ordinary extraction method of N-nitrosodimethylamine in
      beer includes the four steps of low-temperature distillation, liquid-liquid
      extraction, rotary evaporation and nitrogen blowing concentration. With the
      extremely low volume of solvent used, the proposed extraction method proved to be
      easy and simple, and adequate for high-throughput analysis at low cost.

PMID- 25069336
TI  - [Analysis of tartrazine aluminum lake and sunset yellow aluminum lake in foods by
      capillary zone electrophoresis].
AB  - A novel analytical method for tartrazine aluminum lake and sunset yellow aluminum
      lake using capillary zone electrophoresis (CZE) was studied. The pigments
      contained in the color lakes were successfully separated from the aluminum matrix
      in the pre-treatment process, which included the following steps: dissolve the
      color lakes in 0.1 mol/L H2SO4, adjust the pH of the solution to 5.0, then mix it
      with the solution of EDTA x 2Na and heat it in a water bath, then use polyamide
      powder as the stationary phase of solid phase extraction to separate the pigments
      from the solution, and finally elute the pigments with 0.1 mol/L NaOH. The CZE
      conditions systematically optimized for tartrazine aluminum lake were: 48.50 cm
      of a fused silica capillary with 40.00 cm effective length and 50 microm i. d.,
      the temperature controlled at 20.0 degrees C, 29.0 kV applied, HPO4(2-)-PO4(3-)
      (0.015 mol/L, pH 11.45) solution as running buffer, detection at 263 nm. The
      conditions for sunset yellow aluminum lake were: the same capillary and
      temperature, 25.0 kV applied, HPO4(2-)-PO4(3-) (0.025 mol/L, pH 11.45) solution
      as running buffer, detection at 240 nm. The limits of detection were 0.26 mg/L
      and 0.27 mg/L, and the linear ranges were 0.53-1.3 x 10(2) mg/L and 0.54-1.4 x
      10(2) mg/L for tartrazine aluminum lake and sunset yellow aluminum lake,
      respectively. The RSDs were 4.3% and 5.7% (run to run, n = 6), 5.6% and 6.0% (day
      to day, n = 6) for tartrazine aluminum lake and sunset yellow aluminum lake,
      respectively. Further developments for this method could make it a routinely used
      method analyzing color lakes in foods.

PMID- 25069337
TI  - [Transposition of orbital fat and orbicularis muscle flap over the orbital rim
      for correction of lower eyelid pouches complicated with lacrimal groove
      deformity].
AB  - OBJECTIVE: To introduce the experience in the treatment of lower eyelid pouches
      orbital rim. METHODS: An incision was made along the margin of lower eyelid and
      dissection was performed under the orbicularis muscle to expose the orbital
      septum and periosteum of lower orbital rim. The fat released from orbital septum
      was transposed just below the lower orbital rim and fixed on the periosteum. If
      lacrimal groove deformity was not corrected completely, the musculocutaneous
      flap, which may be excised beside the incision, was kept to correct the
      deformities further with only the muscle portion. RESULTS: 72 cases with lower
      eyelid pouches complicated with lacrimal groove deformities were treated with
      transposition of orbital fat and orbicularis muscular flaps. Satisfactory results
      were achieved in all the patients after a follow-up period of 3-6 months.
      CONCLUSION: It is an effective and feasible technique to correct lacrimal groove
      deformities with transposition of orbital fat and orbicularis muscular flaps.

PMID- 25069338
TI  - [Correction of secondary lip whistle deformities and nasal base depression after
      bilateral cleft lip repair with lip subdermal soft tissue flap].
AB  - OBJECTIVE: To explore a new method to correct secondary lip whistle deformities
      and nasal base depression after bilateral complete cleft lip (BCCL) repair with
      lip subdermal soft tissue flap. METHODS: Bilateral subdermal soft tissue "C"
      flaps and "lambda" flap were designed to repair secondary deformities of nasal
      base and reconstruct vermilion tubercle in patients after BCCL repair. RESULTS:
      Good results were achieved in all the patients with primary healing. No flap
      necrosis happened. The result was satisfactory. CONCLUSIONS: With bilateral
      subdermal soft tissue "C" flaps and " lambda" flap, nasal base depression
      deformities and lip whistle deformities can be corrected. It is an ideal method
      for correction of deformities after BCCL repair.

PMID- 25069339
TI  - [Correction of secondary nasal deformity of cleft lip with autogenous costal
      cartilage framework].
AB  - OBJECTIVE: To investigate the correction of secondary nasal deformity of cleft
      lip with autogenous costal cartilage framework. METHODS: 237 cases with secondary
      nasal deformity of unilateral cleft lip were treated. The rib cartilage was
      harvested through a mini-invasive incision, and was fabricated as a C-shaped
      framework, as well as some cartilage fragments. Through transcolumella incision,
      the C-shaped framework was implanted to support the depressed alar and the
      cartilage fragments were used to augment the nasal base. RESULTS: Satisfactory
      cosmetic and functional results were achieved in all the patients with primary
      healing. 93 patients were followed up one year after operation with good cosmetic
      results. CONCLUSIONS: Autogenous costal cartilage framework can be used for the
      correction of secondary nasal deformity of cleft lip with satisfactory results.

PMID- 25069340
TI  - [Mandibular distraction combined with orthognathic techniques for the correction
      of adult hemifacial microsomia].
AB  - OBJECTIVE: To study the combination of Mandibular distraction and orthognathic
      techniques for the reconstruction of adult hemifacial microsomia. METHODS: The
      three-dimensional CT reconstruction data was used with Mimics for preoperation
      design. The osteotomy location, distraction vector, distraction distance were
      decided before operation with a surgical guider. At the first stage, internal
      distractor was implanted after ostetomy through an extra-oral approach. The
      distraction begun 5-7 days after operation with a frequency of 1 mm/day. After
      distraction, the distractor was maintained for 3-6 months. At the second stage,
      the distractor was removed. Le Fort I osteotomy was performed in order to correct
      the cross-bite and improve the facial contour. Usually, bone graft was inserted
      into the gap after Le Fort I osteotomy. The genioplasty was also performed if
      necessary. RESULTS: 9 cases of adult hemifacial microsomia with severe mandibular
      deviation were treated. The facial asymmetry were improved greatly. 1 patient
      suffered an wound infection in the maxillary region after Le Fort I osteotomy and
      healed uneventfully with wound irrigation. CONCLUSIONS: Mandibular distraction
      combined with orthognathic surgery is an effective procedure for adult hemifacial
      microsomia with complicated mandibular hypoplasia.

PMID- 25069341
TI  - [Free superficial iliac circumflex artery skin flap: the clinical application and
      management of donor site defects].
AB  - OBJECTIVE: To investigate the clinical application of free superficial iliac
      circumflex artery skin flaps, as well as the management of donor site defects.
      METHODS: 17 free superficial iliac circumflex artery skin flaps were applied for
      the traumatic defects or deformities on face, neck, foot, hand, ankle and lower
      leg, respectively. The donor site defects were closed directly or covered by
      paraumbilical island flaps. RESULTS: The 17 flap size ranged from 5 cm x 3 cm to
      19 cm x 14 cm. 16 flaps survived completely except 1 flap with partial necrosis,
      which was closed by free skin graft. The donor site defects were closed directly
      in 10 cases, and covered by paraumbilical island flaps in 7 flaps without no flap
      necrosis. The abdomen had a good appearance. CONCLUSIONS: Good appearance can be
      achieved with free superficial iliac circumflex artery skin flaps for the defects
      on face, neck, foot, hand, ankle and lower leg. Paraumbilical island flap can be
      used for the donor site defects.

PMID- 25069342
TI  - [The clinic application of thoracodorsal artery perforator flap: a report of 16
      cases].
AB  - OBJECTIVE: To investigate the effects of free and pedicled thoracodorsal artery
      perforator (TDAP) flaps for repairing skin and soft tissue defects in limbs,
      neck, axillary and shoulder. METHODS: From October 2009 to Auguest 2011, 16 TDAP
      flaps were used to repair skin and tissue defects. Among them, five ipsilateral
      pedicled flaps were used to repair wounds in neck, axillary and shoulder. 11 free
      TDAP flaps were used to repair the wounds with bone or tendon exposure. In 12
      cases, the flaps were pedicled with thoracodorsal artery and vein-lateral
      branches-perforators, in 4 cases, pedicled with thoracodorsal artery and vein
      serratus anterior muscular branches-perforators. The deep fascia, the latissimus
      dorsi and thoracodorsal nerve were not included in all flaps. The flaps size
      ranged from 10 cm x 5 cm to 26 cm x 10 cm. RESULTS: All 16 flaps survived
      completely with primary healing both at donor site and recipent area. After a
      follow-up of 3 to 24 months, all flaps gained good texture and appearance. Only
      linear scar was left at donor area. The shoulder could move freely. CONCLUSIONS:
      TDAP flap has good texture, long vascular pedicle,and reliable blood supply,
      leaving less morbidity at donor site. The latissimus dorsi and thoracodorsal
      nerve are also preserved. The pedicled TDAP flap is an ideal flap for repairing
      the ipsilateral skin and soft tissue defects of the neck, shoulder, axillary. The
      free TDAP flap is suited for repairing skin and soft tissue defects of the
      extremities.

PMID- 25069343
TI  - [Application of thenar perforator flaps for the narrow cicatricial contracture at
      thumb and the first web].
AB  - OBJECTIVE: To discuss the therapeutic effect of thenar perforator flaps for the
      narrow cicatricial contracture at thumb and the first web. METHODS: From Aug.
      2010 to Jan. 2012, 9 cases with narrow cicatricial contracture at thumb and the
      first web, were treated. The defect size after releasing the contracture ranged
      from 8 mm x 20 mm to 15 cm x 30 mm. The bilateral thenar perforator flaps beside
      the wound were designed which size was 10 mm x 25 mm to 15 mm x 35 mm. The wounds
      at donor sites were closed directly. RESULTS: All the 9 flaps survived completely
      with primary healing. The patients were followed up for 6-18 months. The flaps
      had soft texture and good appearance. The shape of flaps and function of the
      fingers were satisfied after 6-18 months of follow-up. There was no scar
      contracture at incisions in thenar. The thumb motion was really normal. The
      abduction of first web was 70 degrees - 90 degrees degrees. CONCLUSIONS: The
      thenar perforator flaps is one of the ideal methods for the treatment of narrow
      cicatricial contracture at thumb and the first web. The main artery is not
      sacrified.

PMID- 25069345
TI  - [Surgical treatment for gyncomastia].
AB  - OBJECTIVE: To introduce different surgical treatment for gyncomastia at different
      grades. METHODS: 37 cases with gynecomastia were divided into three grades as:
      grade I with fat as main tissue, grade II with proliferated fibro-gland as main
      tissue, grade III with big and ptosis breasts and sagging skin. Different
      surgical methods were chosen according to the different grades of gyncomastia.
      These include liposuction, subareolar fibroglandular tissue removing, combined
      technique of the two methods, and breasts resection with free transplantation of
      nipple-areola complex. RESULTS: All patients were satisfied for the appearance of
      post-operative flat male chest. Complications, such as scar, numbness of nipple
      and areola were acceptable for them. CONCLUSIONS: Different surgical methods
      should be chosen for the gynecomastia at different grades. It can improve both
      the physical and psychological problems for patients.

PMID- 25069344
TI  - [Comparative analysis of two surgical techniques for controlling nasal width
      after Le Fort I osteotomy].
AB  - OBJECTIVE: To compare the efficacy of two surgical techniques for controllong
      nasal width after Le Fort I osteotomy. METHODS: Fifty-five patients who received
      the Le Fort I osteotomy have been included in this study. They were randomly
      divided into 2 groups. The experimental group received extraoral ABS, and the
      control group received traditional intraoral ABS. 3D photos of the patient's face
      were taken before operation and at postoperative 3 months. Alar width was
      measured on the 3D photos. Data was reported as means and standard deviations,
      and statistic analysis was done by using student t test. RESULTS: Compared with
      presurgical data, G. lat-G. lat increased by (2.66 +/- 1.47) mm, Al-Al increased
      by (2.20 +/- 1.22) mm and Sbal-Sbal increased by (1.30 +/- 1.33) mm in
      experimental group. G. lat-G. lat increased by (1.38 +/- 1.29) mm, Al-Al
      increased by (1.06 +/- 0.95) mm and Sbal-Sbal increased by (0.36 +/- 1.33) mm in
      the control group. There was significant difference between two groups.
      CONCLUSIONS: The surgical technique of ABS is the most important factor for
      determining the postoperative alar width. Both techniques have better effect on
      the Sbal-Sbal width control than the G. lat-G. lat and Al-Al width control.
      Traditional intraoral ABS can more effectively control the alar width. Both
      techniques cannot completely control the alar base widening after Le Fort I
      osteotomy.

PMID- 25069346
TI  - [Experimental research of hair follicle reconstruction with the aid of embryonic
      mice dermal cells].
AB  - OBJECTIVE: To investigate the effect of embryonic dermal signal on the hair
      inductive capacity of neonatal mice dermal cells which have been amplified in
      vitro. METHODS: Embryonic mice dermal cells of embryonic day 14 were added to a
      chamber on the back of nude mice with neonatal mice dermal cells which had been
      amplified in vitro for 3 days and freshly isolated neonatal mice epidermal cells.
      The hair regeneration was compared between the groups with or without embryonic
      mice dermal cells. Meanwhile, chambers with following cells respectively were
      constructed as controls: embryonic mice dermal cells + neonatal mice epidermal
      cells; freshly isolated neonatal mice dermal cells + neonatal mice epidermal
      cells; amplified neonatal mice dermal cells only; embryonic mice dermal cells
      only; freshly isolated neonatal mice dermal cells only; neonatal mice epidermal
      cells only. RESULTS: The number of regenerated hairs with the aid of embryonic
      mice dermal cells (207 +/- 15. 948) was significantly higher than that (67 +/-
      8.963) in the group without embryonic mice dermal cells (n = 3, t = 7.653, P =
      0.002). CONCLUSION: Embryonic dermal signal can enhance the hair-inductive
      capacity of neonatal mice dermal cells which have been amplified in vitro.

PMID- 25069347
TI  - [The antagonistic effect of folic acid and resveratrol on cleft palate in mice
      induced by TCDD].
AB  - OBJECTIVE: To evaluate whether or not administration of folic acid and
      resveratrol have preventive effects on cleft palate formation as well as the
      comparison of the two drugs' s effects. METHODS: Pregnant mice were randomly
      divided into 9 groups, with 8 mice in each group. The TCDD group mice were dosed
      with TCDD 28 microg/kg body weight on gestation day 10 (GD 10) animals in folic
      acid group were respectively dosed with folic acid 15, 10, 5 mg/kg and TCDD 28
      microg/kg; resveratrol treated mice were divided into 3 groups: resveratrol 50
      mg/kg were orally administered for 6 consecutive days, from gestational day GD 8
      to GD13 in resveratrol (GD8-13 ) group; resveratrol 50 mg/kg were orally
      administered for 6 consecutive days, from gestational day GD 8 to GD13, followed
      hy an oral administered with TCDD on GD10 in resveratrol (GD8-13) + TCDD group;
      resveratrol 50mg/kg and TCDD 28 microg/kg were used by gavage administration at
      GD10 in resveratrol (GD10) + TCDD group. Control mice were treated with the same
      volume of water for 6 consecutive days from GD8 to GD13 and were given a single
      dose of corn oil on GD10. The pregnant mice weight and embryos, the number of
      live, cleft palate, dead and resorption fetal mice were recorded on GD 17.5. The
      coronal sections of the fetal mice heads were prepared at GD 17.5 and observed by
      microscopy. RESULTS: Total frequency of clefts was 92.86% in TCDD group, 84.00%
      (15 mg), 73.08% (10 mg), 84.00% (5 mg) in folic acid + TCDD groups, 0% in
      resveratrol (GD10) group, 74.51% (GD10), 57.78% (GD8-13) in resveratrol + TCDD
      groups. The frequency of cleft was 0% in the control group. Compared with the
      control and the TCDD groups, there were significant differences in the number of
      live, dead and resorption fetal mice in TCCD + resveratrol (GD8-13) group (P <
      0.05). No significant differences in embryonic weight, live fetuses weight, the
      number of live, dead and resorption fetal mice were found in the other groups (P
      > 0.05). CONCLUSION: Test dose of folic acid and resveratrol both had certain
      antagonistic effect on cleft palate in mice induced by TCDD, with folic acid 10
      mg/kg, resveratrol 50 mg/kg GD8-13 doses having stronger antagonistic action.
      Effects of both the two drugs have no significant difference, but resveratrol (50
      mg/kg, GD8-13) significantly affects the fetal mice's growth and development
      under TCDD exposure in utero.

PMID- 25069348
TI  - [Experimental study on the protective effect of anisodamine on flaps with
      ischemia reperfusion injury].
AB  - OBJECTIVE: To observe the effect of anisodamine (Ani) injection on the survival
      rate and histologic result of flaps with ischemia-reperfusion injury, so as to
      demonstrate the protective effect of Ani on the flap survival. METHODS: A total
      of 48 healthy male Wistar rats were randomly divided into model control, normal
      saline(NS) and anisodamine groups, with 16 rats in each group. An 3 cm x 6 cm
      axial flap was formed at the right lower abdomen with abdominal superficial blood
      vessel as the pedicle. 0.5 cm x 0.5 cm skin tissue was taken from the middle part
      of flaps in each group, immediately after operation, 12, 18, 24 h after
      operation. The superoxide dismutase (SOD), nitric oxide (NO), nuclear factor
      kappaB contents in the specimens were detected. The histologic study was also
      performed. The flap survival rate was recorded 7 days after operation. RESULTS:
      Flap survival rate was (78.6 +/- 7.3) % in Anisodamine group. 12, 18, 24 h after
      reperfusion injury, the SOD was (103.3 +/- 3.9), (82.6 +/- 3.8), (67.5 +/- 4.6)
      U/mg; the NO was (5.33 +/- 2.05), (4.75 +/- 1.68), (4.15 +/-1.59) nmol/mg; the NF
      kappaB was 0.211 +/- 0.039, 0.313 +/- 0.033, 0.096 +/- 0.028. The contents of
      SOD, NO and NF-kappaB had the statistical difference of at different time. The
      skin pathological changes in Anisodamine group was obviously better than those in
      NS group. Flap survival rate in Anisodamine group was significantly higher than
      that in NS group. CONCLUSIONS: In the flap with ischemia-reperfusion injury,
      Anisodamine can reduce the damage of free radical, increase the blood flow,
      reduce the production of NF-KB, decrease inflammatory reaction. So Anisodamine
      can increase the survival rate of flaps with ischemia reperfusion injury.

PMID- 25069349
TI  - [Relationship between gene p53 codon 72 polymorphism and pathological scar
      formation after caesarean section].
AB  - OBJECTIVE: To study the relationship between gene p53 codon 72 polymorphism and
      pathological scar formation occurrence after caesarean section. METHODS: The
      method of molecular beacon with real-time PCR was applied to detect gene
      polymorphism of p53 codon 72 in blood samples taken from 303 pregnant women
      (within a week after caesarea section). The clinical visits were taken 3 times
      for 12th to 18th months to ascertain clinical formation of pathological scar and
      its relationship to genotype of p53. The chi-square method was used to analyze
      the relationship of p53 gene polymorphism and abnormal scar formation occurrence
      by statistical software SPSS 13.0. RESULTS: Total of 303 pregnant women were
      assayed. 30 patients were found with pathological scar by clinical visit in the
      total 303 pregnant women. The genotype frequencies of total three types (C/C, C/G
      and G/G) of p53 gene codon 72 in patients with pathological scar are
      significantly different from that of normal pregnant woman. The frequency of C/C
      genotype in patients are higher than that of normal pregnant women (P < 0.01).
      The frequency of C/C genotype in these patients with pathological scar is higher
      (46.7%, 14/30) than C/G (33.0%, 10/30, P < 0.01) or G/G (20%, 6/30) genotype (P <
      0.01). The C allele frequency in the patients is 63.7%. It is also higher than G
      allele (36.7%, P < 0.01). The OR value is 2.30. Therefore the C allele of p53
      gene codon 72 is a risk factor for pathological scar. CONCLUSIONS: There was a
      certain relationship between p53 gene codon 72 C allele and pathological scar
      formation after caesarean section.

PMID- 25069350
TI  - [Tribute to the nurses of the Great War].

PMID- 25069351
TI  - [Nurses during the Great War. A presence across all fronts].

PMID- 25069352
TI  - [Caring for the soldiers of the Great War, the nurses' contribution].
AB  - The notion of the nurse serving in the Great War is very heterogeneous. It is
      important to emphasise the capacity to adapt which these nurses demonstrated.
      During the four years of conflict, they were able to keep up with the many
      changes made to the way casualties were treated.

PMID- 25069353
TI  - [Health problems of combatants during the First World War].
AB  - The First World War because of the use of new weapons, injured more than 3 500
      000 people (500 000 in the face), more than diseases (tuberculosis, typhoid
      fever, etc.) or even weather circumstances. The healing of the war wounds through
      surgery undertook a significant evolution thanks to the use of asepsis and
      antiseptics. Mortality go down, opening the way to the physical and psychological
      rehabilitation of those injured by the war.

PMID- 25069354
TI  - [Nurses in the face of the Great War's epidemics].
AB  - In 1914, nurses were still considered as volunteers. By 1918, given more
      efficient training, they had acquired legitimacy among the French public. Their
      skills and their professionalism were appreciated and recognised, notably thanks
      to the crucial role they played in the fight against the tuberculosis and Spanish
      flu epidemics.

PMID- 25069355
TI  - [Therapeutic advances and nursing practices, 1914-1918].
AB  - The production and transfer of knowledge in the healthcare field were key factors
      which enabled the fight against morbidity and mortality during the First World
      War to be carried out efficiently. The knowledge used to train nurses before the
      war soon became obsolete and had to be updated. Knowledge and practices were
      developed in order to meet as best as possible the specific needs of patients in
      the particular context of this war.

PMID- 25069356
TI  - [A spectacular revolution: evolution of French military health service].
AB  - After the sanitary disaster caused by the first months of the conflict, the
      Health service of the French armies undertook a true revolution. By 1918, it had
      become the most efficient of all the opposing armies. At the end of 1914, through
      the spacing out of the evacuating hospitals within the zone of the armies, the
      most efficient teams were placed as close as possible to the front. Injured
      soldiers were categorized at every step of the chain. Technical progress,
      especially in war surgery, pushed medicine into the moderne era.

PMID- 25069357
TI  - [War casualty triage during the First World War].
AB  - Along with the front hospitals (HOE), the action of sorting out the injured was
      one of the most important innovations of the Great War. Progressively, it was
      implemented and codified on each level of the evacuating chain, with variations
      due to the different phases of the conflict, such as in Verdun or in the Somme.
      From 1917 onwards, specific sorting centers, managed by experimented soldiers,
      were set up in the evacuating hospitals.

PMID- 25069358
TI  - [The armed forces health service and its nurses in the Great War].
AB  - The First World War was characterised by the multitude of battlefields as well as
      by the alternating cycles of offensive phases followed by periods of trench
      warfare. The reality of the fighting, far removed from initial expectations, had
      major repercussions on the organisation of healthcare services. Nurses played a
      central role in the healthcare provided during this conflict.

PMID- 25069359
TI  - [French military nurses during the First World War (1914-1918)].
AB  - In 1914, beingthe heirs of the ambulance soldiers who had been created during the
      time of the Empire, the military males-nurses were overwhelmed by the armies huge
      needs in paramedics. Facing both the callings of commandment which demanded the
      recruitment of soldiers and the necessity--which had been set up as a duty by the
      health service--to attend the doctors, the military male-nurse gave way, in 1918
      to a new comer: the female military nurse.

PMID- 25069360
TI  - [Wound care during the First Word War].
AB  - Following the sanitary disaster which occurred during the first months of First
      Word War, the French Military Health System has structured itself. Focus was made
      on effective surgical sorting for stabilization aids before evacuation. The
      functional prognosis of the war injured individual as his survival has been
      significantly improved. We report nurses' testimonies, for some unpublished yet:
      challenging aids, especially wounds.

PMID- 25069361
TI  - [Treating shell-shocked soldiers in asylums].
AB  - The duration and intensity of the fighting, the soldiers' difficult daily living
      conditions and the high number of men involved in the First World War resulted in
      the appearance of specific mental disorders for some soldiers. At first
      considered to be faking their symptoms, they were later able to be diagnosed and
      treated thanks to psychiatrists' interest in the condition.

PMID- 25069362
TI  - [Nursing figures in the Great War].
AB  - The three Red Cross associations worked hard in France before the First World War
      to prepare nurses to serve during a war. When war broke out, these nurses stepped
      up to the plate. They supported every phase of the war and demonstrated their
      high levels of creativity to overcome the difficult conditions related to the
      fighting.

PMID- 25069363
TI  - [Parisian hospital nurses during the First World War].
AB  - The stereotypical image of the nurse caring for First World War soldiers is of a
      Red Cross volunteer tending to a wounded soldier in a field hospital. In reality,
      the role played by nurses in hospitals far behind the frontline was just as
      crucial. This massive contribution of volunteer nurses influenced the process of
      the professionalisation of nurses in France.

PMID- 25069364
TI  - [Nurses and spies during the First World War].
AB  - During the First World War, some nurses distinguished themselves by playing a
      significant role in spy networks, using their activity as a cover. They took an
      active part in the setting up of escape routes for allied prisoners of war and
      the gathering of intelligence on the positions of German troops, in particular in
      Belgium and northern France. Among them Edith Cavell, Gabrielle Petit, Louise de
      Bettignies, Marie-Leonie Vanhoutte, Marthe Cocknaert and Emilienne-Rose
      Ducimetiere are considered as heroines.

PMID- 25069365
TI  - [Order of Malta during First World War].
AB  - The sovereign Military Order of Malta is one of the oldest humanitarian
      organizations still existing today The First World War gave it the opportunity to
      prove its large knowledge of emergency medicine, under exceptional circumstances,
      from the front to the hospitals at the back of the front. On all parts of the
      European conflict the Order took care of more than 800 000 victims of the war.

PMID- 25069366
TI  - [Beatrice Allsop, a nurse on the Western Front].
AB  - Beatrice Allsop was one of the first nurses to receive a military medal for her
      bravery. Wounded in Bethune, when her casualty clearing station was shelled, she
      continued working until all her patients had been evacuated and the team of
      nurses transferred. She is emblematic of the thousands of nurses who volunteered
      for military service at the beginning of the Great War. Her example testifies to
      the spirit which drove these women serving on the Western Front.

PMID- 25069367
TI  - [The Canadian military nurses of the Great War].
AB  - During the Great War, Canada deployed military nurses, like the other dominions
      of the British Empire. The "bluebirds" were the first nurses awarded the status
      of officer. Underprepared for war, they were able to adapt themselves in order to
      carry out the missions entrusted to them.

PMID- 25069368
TI  - [The Australian nurses in France during the Great War].
AB  - Australia was dragged into the First World War due to its status as a dominion of
      the British Empire. High numbers of nurses, both civilian and military, served
      during this conflict, notably in France, reflecting the surge of support and
      sympathy felt by Australians for the country.

PMID- 25069369
TI  - [German nurses during the First World War].
AB  - Nurses from several German organisations participated in the First World War. For
      the most part, they did not work on the frontline but at the rear, in hospital
      trains, hospitals or refugee camps. They cared forwounded soldiers and faced
      epidemics of infectious diseases. The journal of the national association of
      nurses, which continued to be published during the war, provides a snapshot of
      their concerns and their questioning regarding the profession and its evolution.

PMID- 25069370
TI  - [Contribution of the US Army Nurse Corps to the First World War].
AB  - A number of American nurses, on an individual basis, gave their assistance to
      European countries as soon as war was declared, in 1914. In 1917, when the United
      States entered the war, nurses from the American army arrived on the European
      continent before the troops. They made a major contribution to the conflict, as
      testified by the numerous medals they were awarded.

PMID- 25069371
TI  - [The nurses on the Yser front, 1914-1918].
AB  - During the First World War, two hundred nurses served in the Ambulance de
      l'Ocean, a military hospital located in La Panne, in Belgium, near the Yser
      front. The innovative organisation of the hospital, the specialisation of the
      services and the work accomplished there led to nurses being recognised as
      essential partners in the provision of medical care.

PMID- 25069372
TI  - [The Italian armed forces health service during the Great War].
AB  - The Great War had a huge impact on Italian society. The organisation of the armed
      forces health service faced extreme difficulties due to the extensive loss of
      life of an almost exclusively terrestrial war. In this context, the role of the
      medical staff and nursing staff was essential, as the example of the volunteer
      Red Cross nurses testifies. However, this conflict revealed the need to improve
      the training of the nursing staff, as was the case in Anglo-Saxon countries.

PMID- 25069374
TI  - [The First World War and French nurses].
AB  - The First World War changed the place of women in French society. The major
      contribution they made in numerous sectors of activity is indisputable. However,
      the process of professionalisation was not really undertaken and the level of
      training given to the nurses, most of whom were volunteers, was very sketchy. The
      nurses seemed to be appreciated as much for their dedication as for their skills.

PMID- 25069373
TI  - [The International Council of Nurses during the First World War].
AB  - The outbreak of the First World War and the four years of conflict disrupted the
      activities of the International Council of Nurses (ICN). The results obtained
      before the war, notably with regard to the improvement of women's working
      conditions, were thrown into question, and the international spirit which
      characterised the ICN was threatened. After the war, nurses were nevertheless
      considered as having a key role to play in public healthcare.

PMID- 25069375
TI  - [Elements of bibliography].

PMID- 25069376
TI  - Rh-null phenotype caused by a complete RHAG deletion.

PMID- 25069377
TI  - Black and white with some shades of grey: the diverse responses of inducible
      metabolic pathways in Escherichia coli.
AB  - The metabolic pathways for many sugars are inducible. This process has been
      extensively studied in the case of Escherichia coli lactose metabolism. It has
      long been known that gratuitous induction of the lac operon with non
      metabolizable lactose analogues generates an all-or-nothing response, where some
      cells express the lac genes at a maximal rate and others not at all. However, the
      response to lactose itself is graded, where all cells express the lac genes in
      proportion to lactose concentrations. The mechanisms generating these distinct
      behaviours in lactose metabolism have been a topic of many studies. Despite this
      large body of work, little is known about how other pathways respond to their
      cognate sugars. An article of Molecular Microbiology investigated the response of
      eight metabolic pathways in E. coli to their cognate sugars at single-cell
      resolution. The authors demonstrate that these pathways exhibit diverse
      responses, ranging from graded to all-or-nothing responses and combinations
      thereof. Remarkably, they were able to interpret these responses using a simple
      mathematical model and identify the mechanisms likely giving rise to each. 

PMID- 25069378
TI  - Superimposed linear lichen planus in a 4-year-old girl.

PMID- 25069382
TI  - Screening for Chlamydia infection in a sexually transmitted infection clinic: a
      missed opportunity?
AB  - OBJECTIVES: Chlamydia trachomatis (CT) infection is the most common sexually
      transmitted infection (STI) reported in Europe. We aim to evaluate the overall
      prevalence of CT infection and the rate of asymptomatic infection in an STI
      clinic over a 5-year period. We will also discuss screening strategies with
      reference to attendees diagnosed with an STI and their sexual partners, and
      attendees with a non-infectious genital dermatosis. METHODS: Clinical and
      laboratory data for all attendees at a university hospital STI clinic over a 5
      year period were reviewed. Diagnosis of CT infection was made upon polymerase
      chain reaction (PCR) performed in first-void urine. RESULTS: The overall
      prevalence of CT infection was 4.0% (53/1310); the rate of asymptomatic infection
      was 84.9% (45/53). The prevalence of CT infection among attendees with an STI
      diagnosis and their sexual partners was 5.2% (50/963), whereas that among
      attendees with a non-infectious genital dermatosis was 0.9% (3/347; P < 0.001).
      Infected attendees were younger than attendees without CT infection (median age:
      31 years vs. 40 years; P < 0.001). In 39.5% (17/43) of CT-infected attendees, it
      was possible to notify a sexual partner; CT infection was subsequently diagnosed
      in 58.8% (10/17) of partners. CONCLUSIONS: Asymptomatic CT infection had a
      representative frequency, which was more pronounced among young attendees with an
      STI diagnosis and their sexual partners, to whom screening should be offered.
      Issues of age limits for screening and whether screening should be directed to
      males in non-STI clinic settings should be carefully assessed.

PMID- 25069381
TI  - Mechanisms and assessment of statin-related muscular adverse effects.
AB  - Statin-associated muscular adverse effects cover a wide range of symptoms,
      including asymptomatic increase of creatine kinase serum activity and life
      threatening rhabdomyolysis. Different underlying pathomechanisms have been
      proposed. However, a unifying concept of the pathogenesis of statin-related
      muscular adverse effects has not emerged so far. In this review, we attempt to
      categorize these mechanisms along three levels. Firstly, among pharmacokinetic
      factors, it has been shown for some statins that inhibition of cytochrome P450
      mediated hepatic biotransformation and hepatic uptake by transporter proteins
      contribute to an increase of systemic statin concentrations. Secondly, at the
      myocyte membrane level, cell membrane uptake transporters affect intracellular
      statin concentrations. Thirdly, at the intracellular level, inhibition of the 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased
      intracellular concentrations of downstream metabolites (e.g. selenoproteins,
      ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine
      receptor 3, glycine amidinotransferase). We also review current recommendations
      for prescribers. 

PMID- 25069383
TI  - The correlation between the presence of viremia and clinical severity in patients
      with enterovirus 71 infection: a multi-center cohort study.
AB  - BACKGROUND: Enterovirus 71 (EV71) is a great disease burden across the whole
      world, particularly in Southeast Asia. However, in recent decades, the
      pathogenesis of severe EV71 infection was not well understood. This study was
      aimed to investigate the correlation between the presence of viremia and the
      clinical severity of EV71 infection. METHODS: We organized a prospective cohort
      study and enrolled laboratory-confirmed EV71 cases in six tertiary care hospitals
      in Taiwan during the EV71 epidemic from 2011 to 2012. Blood samples were
      collected once in the acute stage, on the first day of admission. We used real
      time RT-PCR to detect EV71 viremia. Demographical and clinical data were
      collected and the clinical severity was categorized into four grades. Data
      analysis was performed to identify the risk factors of viremia and the
      correlation between viremia and clinical severity of EV71 infection. RESULTS: Of
      the total 224 enrolled patients, 59 (26%) patients were confirmed to have
      viremia. Two-thirds (68%) of viremic cases were detected within the first three
      days of infection. Viremia occurred more frequently in children under the age of
      one year old (odds ratios [OR] 4.82, p < 0.001) but the association between the
      presence of viremia and complicated EV71 infection was not found (OR 1.02, p =
      0.96). In the viremia group, patients had significantly more severe complications
      if viremia was detected after the third day of disease onset (26% vs. 5%, p =
      0.03). CONCLUSIONS: Viremia occurred more frequently in children under the age of
      one year and viremia detected beyond three days after the onset of disease
      correlated with more severe disease in EV71 patients.

PMID- 25069384
TI  - Incorporation of a clot-binding peptide into polythiophene: properties of
      composites for biomedical applications.
AB  - Biocomposites formed by a pentapeptide (CREKA), which recognizes clotted plasma
      proteins, entrapped into the poly(3,4-ethylenedioxythiophene) (PEDOT) matrix have
      been prepared using three very different procedures. X-ray photoelectron
      spectroscopy analyses indicate that PEDOT-CREKA films, prepared by
      chronoamperometry in basic aqueous solution (pH = 10.3) and deposited onto a
      PEDOT internal layer, present the higher concentration of peptide: one CREKA
      molecule per six polymer repeat units. The surface of this bilayered system shows
      numerous folds homogeneously distributed, which have been exhaustively
      characterized by scanning electron microscopy and atomic force microscopy.
      Indeed, the morphology and topography of such bilayered films is completely
      different from those of biocomposite-prepared acid aqueous and organic solutions
      as polymerization media. The impact of the entrapped peptide molecules in the
      electrochemical properties of the conducting polymer has been found to be
      practically negligible. In contrast, biocompatibility assays with two different
      cellular lines indicate that PEDOT-CREKA favors cellular proliferation, which has
      been attributed to the binding of the peptide to the fibrin molecules from the
      serum used as a supplement in the culture medium. The latter assumption has been
      corroborated examining the ability of PEDOT-CREKA to bind fibrin. The latter
      ability has been also used to explore an alternative strategy based on the
      treatment of PEDOT-CREKA with fibrin to promote cell attachment and growth.
      Overall, the results suggest that PEDOT-CREKA is appropriated for multiple
      biomedical applications combining the electrochemical properties of conducting
      polymer and the ability of the peptide to recognize and bind proteins. 

PMID- 25069385
TI  - A prospective study of acute inpatient gout diagnoses and management in a
      tertiary hospital: the determinants and outcome of a rheumatology consultation.
AB  - BACKGROUND: Despite acute gout frequently complicating hospital admissions,
      diagnosis and management are variable. Rheumatology input may improve patient
      outcomes. AIM: To examine acute episodes of inpatient gout in a tertiary hospital
      to determine (i) factors that may lead to rheumatology input being sought and
      (ii) the differences in outcomes when rheumatology input occurs. METHODS: Data
      collection occurred between February and October 2012 for inpatients in a
      tertiary Australian hospital. Data were prospectively collected for all
      rheumatology consultations with a diagnosis of gout. Subjects who had an
      inpatient admission complicated by acute gout and who did not have rheumatology
      input were identified through health information coding from discharge summaries.
      RESULTS: Fifty-eight patients (41% with rheumatology input) were included in the
      study. Rheumatology input was significantly more likely when the patient was
      younger (68.9 years vs 78.4 years; P = 0.04) with knee joint involvement (41.7%
      vs 3.0%; P < 0.001). When rheumatology input occurred, subjects were more likely
      to have had a serum urate measured (83% vs 50%; P = 0.009), joint aspiration
      performed (54.2% vs 0%; P < 0.001), been prescribed acute gout medications at
      discharge (95.8% vs 61.3%; P = 0.001), a documented discharge plan (91.7% vs
      23.5%; P < 0.001) and outpatient follow up (41.7% vs 0%; P < 0.001). CONCLUSION:
      Among inpatients with acute gout, rheumatology input was more likely to be sought
      in younger patients with knee joint disease. When rheumatology input occurred,
      patients were more likely to have a synovial fluid confirmed diagnosis of gout
      with appropriate acute management and a follow-up plan.

PMID- 25069386
TI  - Dienogest in the treatment of endometriosis.
AB  - INTRODUCTION: Dienogest (DNG) is an oral progestin, derivative of 19
      nortestosterone, that has recently been introduced for the treatment of
      endometriosis. AREAS COVERED: This review examines the clinical efficacy, safety
      and tolerability of DNG in the treatment of endometriosis. The material included
      in the current manuscript was searched and obtained via Medline, Pubmed and
      EMBASE, from inception until February 2014. The term 'dienogest' was associated
      with the following search terms: 'endometriosis', 'pharmacokinetics', 'safety'
      and 'efficacy'. EXPERT OPINION: Several trials demonstrated the clinical
      efficacy, safety and tolerability of DNG. However the use of DNG is associated
      with some limitations. So far, no study investigated the potential of
      contraceptive effect of this treatment and therefore, it should be recommended
      with other methods of contraception (e.g., barrier methods). A further limitation
      of the use of DNG as daily therapy in the long term is that the cost of the
      therapy is higher than other progestins available on the market and combined oral
      contraceptives. Therefore, future studies should be designed to compare the
      efficacy and safety of DNG with other progestins.

PMID- 25069387
TI  - Rivaroxaban vs. low molecular weight heparin for the prevention of venous
      thromboembolism after hip or knee arthroplasty: a cohort study.
AB  - BACKGROUND: Rivaroxaban is increasingly used to prevent venous thromboembolism
      after hip or knee arthroplasty. Studies evaluating the effectiveness of
      rivaroxaban compared to low molecular weight heparin after orthopedic surgery in
      routine practice are scarce. PATIENTS AND METHODS: We conducted a retrospective
      cohort study in 121 hospitals in Ontario, Canada, between 2002 and 2012. We
      included patients aged 66 years or older (median age 73 years) who received an
      outpatient prescription for subcutaneous low molecular weight heparin (n = 11
      471) or oral rivaroxaban (n = 12 850) on hospital discharge after a total knee or
      hip arthroplasty. The two coprimary outcomes assessed within 30 days of the
      prescription date were emergency department visit or hospitalization with venous
      thromboembolism (either deep vein thrombosis or pulmonary embolism; primary
      efficacy outcome) and a hospitalization with non-traumatic major hemorrhage
      (primary safety outcome). RESULTS: Rivaroxaban use increased over the study
      period. Compared to low molecular weight heparin, rivaroxaban was associated with
      a lower 30-day risk of hospitalization with venous thromboembolism (0.47% vs.
      0.81%; relative risk 0.58; 95% confidence interval 0.42-0.81; P = 0.001) with no
      significant difference in hospitalizations for major bleeding (0.18% vs. 0.20%;
      relative risk 0.89; 95% confidence interval 0.50-1.59; P = 0.700). CONCLUSIONS:
      In routine practice, anticoagulant prophylaxis with rivaroxaban compared to low
      molecular weight heparin after hospital discharge from total hip or knee
      arthroplasty is associated with a lower risk of symptomatic venous
      thromboembolism with no difference in the risk of bleeding.

PMID- 25069388
TI  - Clinical analysis of secondary acquired cholesteatoma.
AB  - OBJECTIVE: This study aimed to analyze the clinical features of patients who
      underwent surgery for secondary acquired cholesteatoma (SAC). MATERIALS AND
      METHODS: The subjects were 30 patients who underwent surgery for SAC in 30 ears.
      We investigated the age distribution, sex, tympanic membrane (TM) findings,
      temporal bone pneumatization, morphology of TM epidermis invasion, extent of
      cholesteatoma invasion, ossicular erosion, surgical methods and surgical results.
      RESULTS: There were 10 males (33.3%) and 20 females (66.6%), with a mean age 54.9
      years. The TM perforation was medium-sized or larger in 27 ears (90%). Temporal
      bone pneumatization was poor or bad in 90% (18/20) of the evaluated ears. The
      cholesteatoma invaded from the malleus manubrium to the promontory in 23 ears
      (76.7%). There were no patients in whom the cholesteatoma invaded the antrum or
      mastoid. The ossicles were affected in 19 ears (63.3%). Ossiculoplasty with a
      columella on the stapes was the most frequent procedure, performed for 16 ears
      (53.3%). There were no hearing results with a postoperative air-bone gap of more
      than 31 dB. CONCLUSIONS: Although SAC is rare, it is important for the clinician
      to keep this type of cholesteatoma in mind.

PMID- 25069389
TI  - Rhinosinusitis in children: a comparison of patients requiring surgery for acute
      complications versus chronic disease.
AB  - BACKGROUND: Patient characteristics, risk factors, and microbiology are important
      to consider in the management of complications of acute bacterial sinusitis (ABS)
      in pediatric patients. This study evaluates this subset of patients and compares
      them to patients that undergo surgery for chronic rhinosinusitis (CRS). METHODS:
      This study is a retrospective review of all pediatric patients from 2002 to 2011,
      who underwent sinus surgery at a tertiary hospital. Patients who underwent
      surgery for ABS complication were compared to patients who underwent surgery for
      CRS. Statistical analysis was completed using chi-square test or Fisher's exact
      test with a statistical significance set at p<0.05. RESULTS: Twenty-seven
      patients with a complication of ABS and 77 patients with CRS were analyzed. The
      groups did not differ demographically. Patients with a complication were
      statistically less likely to have seasonal allergies, prior sinusitis, prior
      nasal steroid use, or adenoidectomy (p<0.05). In addition, they had more frequent
      involvement of ethmoid and frontal sinuses (p<0.05). The most common cultures
      results were no growth (30.8%), Streptococcus milleri (30.8%), and normal flora
      (19.2%) in ABS for the with a complication group, and normal flora (41.5%),
      coagulase negative Staphylococcus (22%), and Propionobacterium (19.5%) for the
      CRS group. Most prevalent complications were preseptal cellulitis (55.5%),
      orbital subperiosteal abscess (29.6%), subgaleal abscess (22%), and epidural
      abscess (22%). Five patients had simultaneous orbital and intracranial
      complications. CONCLUSIONS: Patients who present with complications of ABS vary
      significantly from the CRS patients. Location of most commonly affected sinuses
      and microbiology also differ and is crucial for understanding the management of
      this disease process.

PMID- 25069391
TI  - Anomalous photoelectric effect of a polycrystalline topological insulator film.
AB  - A topological insulator represents a new state of quantum matter that possesses
      an insulating bulk band gap as well as a spin-momentum-locked Dirac cone on the
      surface that is protected by time-reversal symmetry. Photon-dressed surface
      states and light-induced surface photocurrents have been observed in topological
      insulators. Here, we report experimental observations of an anomalous
      photoelectric effect in thin films of Bi2Te3, a polycrystalline topological
      insulator. Under illumination with non-polarised light, transport measurements
      reveal that the resistance of the topological surface states suddenly increases
      when the polycrystalline film is illuminated. The resistance variation is
      positively dependent on the light intensity but has no relation to the applied
      electric field; this finding can be attributed to the gap opening of the surface
      Dirac cone. This observation of an anomalous photoelectric effect in
      polycrystalline topological insulators offers exciting opportunities for the
      creation of photodetectors with an unusually broad spectral range. Moreover,
      polycrystalline topological insulator films provide an attractive material
      platform for exploring the nature and practical application of topological
      insulators. 

PMID- 25069390
TI  - Metabolic syndrome and renal cell carcinoma.
AB  - BACKGROUND: Metabolic syndrome (MS) is a cluster of metabolic abnormalities,
      which has been regarded as a pivotal risk factor for cardiovascular diseases.
      Recent studies focusing on the relationship between MS and cancer have recognized
      the significant role of MS on carcinogenesis. Likewise, growing evidence suggests
      that MS has a strong association with increased renal cell carcinoma (RCC) risk.
      This review outlines the link between MS and RCC, and some underlying mechanisms
      responsible for MS-associated RCC. MATERIALS AND METHODS: A National Center for
      Biotechnology Information PubMed search (http://www.pubmed.gov) was conducted
      using medical subject headings 'metabolic syndrome', 'obesity', 'hypertension',
      'diabetes', 'dyslipidemia', and 'renal cell carcinoma'. RESULTS: This revealed
      that a variety of molecular mechanisms secondary to MS are involved in RCC
      formation, progression, and metastasis. A deeper understanding of these molecular
      mechanisms may provide some strategies for the prevention and treatment of RCC.
      CONCLUSIONS: In summary, there is a large body of evidence regarding the link
      between MS and RCC, within which each component of MS is considered to have a
      close causal association with RCC.

PMID- 25069392
TI  - Fetal alcohol programming of hypothalamic proopiomelanocortin system by
      epigenetic mechanisms and later life vulnerability to stress.
AB  - Hypothalamic proopiomelanocortin (POMC) neurons, one of the major regulators of
      the hypothalamic-pituitary-adrenal (HPA) axis, immune functions, and energy
      homeostasis, are vulnerable to the adverse effects of fetal alcohol exposure
      (FAE). These effects are manifested in POMC neurons by a decrease in Pomc gene
      expression, a decrement in the levels of its derived peptide beta-endorphin and a
      dysregulation of the stress response in the adult offspring. The HPA axis is a
      major neuroendocrine system with pivotal physiological functions and mode of
      regulation. This system has been shown to be perturbed by prenatal alcohol
      exposure. It has been demonstrated that the perturbation of the HPA axis by FAE
      is long-lasting and is linked to molecular, neurophysiological, and behavioral
      changes in exposed individuals. Recently, we showed that the dysregulation of the
      POMC system function by FAE is induced by epigenetic mechanisms such as
      hypermethylation of Pomc gene promoter and an alteration in histone marks in POMC
      neurons. This developmental programming of the POMC system by FAE altered the
      transcriptome in POMC neurons and induced a hyperresponse to stress in adulthood.
      These long-lasting epigenetic changes influenced subsequent generations via the
      male germline. We also demonstrated that the epigenetic programming of the POMC
      system by FAE was reversed in adulthood with the application of the inhibitors of
      DNA methylation or histone modifications. Thus, prenatal environmental
      influences, such as alcohol exposure, could epigenetically modulate POMC neuronal
      circuits and function to shape adult behavioral patterns. Identifying specific
      epigenetic factors in hypothalamic POMC neurons that are modulated by fetal
      alcohol and target Pomc gene could be potentially useful for the development of
      new therapeutic approaches to treat stress-related diseases in patients with
      fetal alcohol spectrum disorders. 

PMID- 25069393
TI  - 'Relieved Working' study: systematic development and design of an intervention to
      decrease occupational quartz exposure at construction worksites.
AB  - BACKGROUND: Occupational quartz exposure continues to be a serious hazard in the
      construction industry. Until now, evidence-based interventions aimed at reducing
      quartz exposure are scarce. The aim of this study was to systematically develop
      an intervention and to describe the study to evaluate its effectiveness.
      METHODS/DESIGN: The intervention was developed according to the principles of the
      Intervention Mapping protocol, meaning that evidence from the literature was
      combined with information collected from stakeholders (e.g., construction
      workers, managers and researchers). The intervention aimed to integrate
      technical, behavioural and organizational factors. The intervention consists of
      two plenary meetings for all employers within the company, and individual visits
      at construction worksites, including specific intervention materials.
      Additionally, a demonstration session regarding control measures was organized
      for all managers. The effectiveness of the intervention will be evaluated in a
      cluster randomized controlled trial among eight construction companies, with
      measurements at baseline and follow-up. Outcome measures are personal respirable
      dust and quartz exposure by means of exposure assessment, and behavioural and
      organizational determinants which will be assessed by means of questionnaires.
      Additionally, a process evaluation will shed light on whether the intervention
      (does not) works, and, if so, the reasons for this. DISCUSSION: Applying
      Intervention Mapping in the development of an intervention to reduce occupational
      quartz exposure was useful, as different stakeholders provided input for the
      intervention as well as the implementation strategy. Therefore, the feasibility
      of the intervention has been enhanced, as it appeals to construction workers and
      managers and will not unduly interfere with the ongoing construction work. TRIAL
      REGISTRATION NUMBER: NTR4586 (May 7th 2014).

PMID- 25069395
TI  - Erythropoietin: friend and foe!

PMID- 25069394
TI  - Effects of blood transfusion on cytokine profile and pulmonary function in
      patients with thalassemia major.
AB  - BACKGROUND AND AIMS: Thalassemia major (TM) is characterized by abnormal
      hemoglobin synthesis, which results in decreased oxygen delivery to the tissues,
      ineffective erythropoiesis and iron overload. The purpose of this study was to
      find out the predominant type of lung mechanical abnormalities in TM patients,
      the prevalence of the change in pulmonary diffusing capacity and to search the
      association of cytokines with pulmonary function tests (PFTs). METHODS: TM
      patients (n = 26) who were on regular transfusion program were included in the
      study. Pretransfusional and posttransfusional PFTs were performed. Before
      transfusion, blood samples were collected for complete blood count, serum
      ferritin, zinc, transforming growth factor-beta1 (TGF-beta1), interleukin (IL)-8
      and IL-10 levels. RESULTS: Obstructive lung pattern was the predominant pulmonary
      sequela. Male gender was the main risk factor for pulmonary function abnormality.
      Because of very low values, serum IL-10 levels of all patients were undetectable,
      and serum IL-8 levels could be measured only in six patients. Median serum IL-8
      level was higher in patients with abnormal PFT. Pretransfusional single breath
      diffusion of carbon monoxide (DLCO ) correlated negatively with serum TGF-beta1
      and ferritin levels. After transfusion, there was a statistically significant
      decrease in forced expiratory volume in 1 s, forced expiratory flow between 25%
      and 75% of vital capacity, and airway conductance but significant increase in
      DLCO . CONCLUSIONS: Although they are mostly asymptomatic, TM patients have
      important PFT abnormalities. Blood transfusion may have an acute deleterious
      effect on pulmonary functions. The disturbed pulmonary functions were found to
      correlate with IL-8 and TGF-beta levels. Relations of different cytokines with
      different PFT parameters suggest that the immune system is effective pulmonary
      dysfunction.

PMID- 25069396
TI  - Mammary filariasis masquerading as breast carcinoma.

PMID- 25069397
TI  - A review on possible elicitor molecules of cyanobacteria: their role in improving
      plant growth and providing tolerance against biotic or abiotic stress.
AB  - Cyanobacteria are prominent inhabitants of many agricultural soils, where they
      potentially contribute towards biological nitrogen fixation, help in phosphate
      solubilization and mineral release to improve soil fertility and crop
      productivity. However, beside naturally fertilizing and balancing mineral
      nutrition in the soil, many cyanobacteria are known to release various kinds of
      biologically active substances like proteins, vitamins, carbohydrates, amino
      acids, polysaccharides and phytohormones that function as elicitor molecules to
      promote plant growth and help them to fight against biotic and abiotic stress.
      These metabolites produced by the cyanobacteria affect the gene expression of the
      host plants and thereby bring about qualitative and quantitative changes in the
      phytochemical composition of the plants. Experiments carried out with live
      inoculum or with the extracts of cyanobacterial strains on several plant species,
      such as rice, wheat, maize, cotton etc., have demonstrated the synthesis of
      signalling metabolites. Thus, in view of its beneficial effect, this paper
      reviews the role of cyanobacteria in triggering the growth and development of
      plants and hence its utilization in agriculture. 

PMID- 25069398
TI  - Spectroscopic tracking of Schiff base compounds' hydrogen bonding reorganization
      associated with solid-to-solid phase transition.
AB  - A series of 2,6-dihydroxynaphthalene-1-methylidene alkylamines whose alkyl chain
      lengths ranged from 9 to 12 was spectroscopically examined. Transmission
      ultraviolet-visible absorption microspectroscopy revealed that the spectra of
      solid thin-films of the crystalline samples showed two distinct profiles
      depending on polymorphs as well as on alkyl chain length. We concluded that these
      spectral changes occurred not because of conventional intramolecular proton
      transfer but because of the molecules' interactions with an external proton
      source, that is, the intermolecular proton transfer. The spectral changes were
      accompanied by changes in the intermolecular hydrogen bonding network. When a
      crystal of a sample compound was heated, its spectrum changed dramatically before
      the crystal underwent a solid-to-solid phase transition to another polymorph. We
      concluded that these spectral changes indicated strengthening of intermolecular
      hydrogen bonding or intermolecular proton transfer, which would have triggered a
      drastic change in the hydrogen bonding network structure. 

PMID- 25069399
TI  - Paediatric palliative care by video consultation at home: a cost minimisation
      analysis.
AB  - BACKGROUND: In the vast state of Queensland, Australia, access to specialist
      paediatric services are only available in the capital city of Brisbane, and are
      limited in regional and remote locations. During home-based palliative care, it
      is not always desirable or practical to move a patient to attend appointments,
      and so access to care may be even further limited. To address these problems, at
      the Royal Children's Hospital (RCH) in Brisbane, a Home Telehealth Program (HTP)
      has been successfully established to provide palliative care consultations to
      families throughout Queensland. METHODS: A cost minimisation analysis was
      undertaken to compare the actual costs of the HTP consultations, with the
      estimated potential costs associated with face-to face-consultations occurring by
      either i) hospital based consultations in the outpatients department at the RCH,
      or ii) home visits from the Paediatric Palliative Care Service. The analysis was
      undertaken from the perspective of the Children's Health Service. The analysis
      was based on data from 95 home video consultations which occurred over a two year
      period, and included costs associated with projected: clinician time and travel;
      costs reimbursed to families for travel through the Patients Travel Subsidy (PTS)
      scheme; hospital outpatient clinic costs, project co-ordination and equipment and
      infrastructure costs. The mean costs per consultation were calculated for each
      approach. RESULTS: Air travel (n = 24) significantly affected the results. The
      mean cost of the HTP intervention was $294 and required no travel. The estimated
      mean cost per consultation in the hospital outpatient department was $748. The
      mean cost of home visits per consultation was $1214. Video consultation in the
      home is the most economical method of providing a consultation. The largest costs
      avoided to the health service are those associated with clinician time required
      for travel and the PTS scheme. CONCLUSION: While face-to-face consultations are
      the gold standard of care, for families located at a distance from the hospital,
      video consultation in the home presents an effective and cost efficient method to
      deliver a consultation. Additionally video consultation in the home ensures
      equity of access to services and minimum disruption to hospital based palliative
      care teams.

PMID- 25069401
TI  - Spatially organized partial synchronization through the chimera mechanism in a
      network of electrochemical reactions.
AB  - Detailed experimental and numerical results are presented about the pattern
      formation mechanism of spatially organized partially synchronized states in a
      networked chemical system with oscillatory metal dissolution. Numerical
      simulations of the reaction system are used to identify experimental conditions
      (heterogeneity, network topology, and coupling time-scale) under which the
      chemical reactions, which take place in a network, are split into coexisting
      coherent and incoherent domains through the chimera mechanism. Experiments are
      carried out with a network of twenty electrodes arranged in a ring with seven
      nearest neighbor couplings in both directions along the ring. The patterns are
      characterized by analyzing the oscillation frequencies and entrainments to the
      mean field of the phases of oscillations. The chimera state forms from two
      domains of elements: the chimera core in which the elements have identical
      frequencies and are entrained to their corresponding mean field and the chimera
      shell where the elements exhibit desynchrony with each other and the mean field.
      The experiments point out the importance of low level of heterogeneities (e.g.,
      surface conditions) and optimal level of coupling strength and time-scale as
      necessary components for the realization of the chimera state. For systems with
      large heterogeneities, a 'remnant' chimera state is identified where the pattern
      is strongly affected by the presence of frequency clusters. The exploration of
      dynamical features with networked reactions could open up ways for identification
      of novel types of patterns that cannot be observed with reaction diffusion
      systems (with localized interactions) or with reactions under global constraints,
      coupling, or feedback. 

PMID- 25069400
TI  - Quality of life after major trauma with multiple rib fractures.
AB  - INTRODUCTION: Rib fractures are a common injury presenting to major trauma
      centres and community hospitals. Aside from the acute impact of rib fracture
      injury, longer-term morbidity of pain, disability and deformity have been
      described. Despite this, the mainstay of management for the vast majority of rib
      fracture injuries remains supportive only with analgesia and where required
      respiratory support. This study aimed to document the long-term quality of life
      in a cohort of major trauma patients with rib fracture injury over 24 months.
      METHODS: Retrospective review (July 2006-July 2011) of 397 major trauma patients
      admitted to The Alfred Hospital with rib fractures and not treated with operative
      rib fixation. The main outcome measures were quality of life over 24 months post
      injury assessed using the Glasgow Outcome Scale Extended and SF12 health
      assessment forms and a pain questionnaire. RESULTS: Assessment over 24 months of
      major trauma patients with multiple rib fractures demonstrated significantly
      lower quality of life compared with published Australian norms at all time points
      measured. Return to work rates were poor with only 71% of those who were working
      prior to their accident, returning to any work. CONCLUSIONS: This study
      demonstrates a significant reduction in quality of life for rib fracture patients
      requiring admission to hospital, which does not return to the level of Australian
      norms for at least two years.

PMID- 25069402
TI  - Neuronal nitric oxide synthase, as a downstream signaling molecule of c-jun,
      regulates the survival of differentiated PC12 cells.
AB  - The high expression of c-jun and neuronal nitric oxide synthase (nNOS) generally
      occurs in neurons following the generation of various animal models of central
      neuronal diseases. However, the mechanism between them in neuronal disease
      remains to be elucidated. Our previous studies demonstrated that the expression
      of c-jun always occurs prior to expression of nNOS in motoneuron injuries and
      suppression of c-jun expression by c-jun siRNA decreased nNOS expression in
      differentiated PC12 cells. The present study aimed to examine whether there was
      an association of up and downstream regulation or crosstalk between c-jun and
      nNOS in neurons. Using a culture of differentiated PC12 cells in vitro, the
      expression of nNOS and c-jun in cells was investigated by immunofluorescence. The
      nNOS inhibitor 7-nitroindazole (7-NI) was used in differentiated PC12 cells to
      downregulate the expression of nNOS. The optimal concentration of 7-NI on the
      viability and survival of cultured differentiated PC12 cells was selected using a
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and the effects of 7
      NI on the activity of constitutive nitric oxide synthase (cNOS) in differentiated
      PC12 cells were determined using a NOS Activity Detection kit. The effects of 7
      NI on the gene expression of nNOS and c-jun were detected by western blot
      analysis. The results from the immunofluorescence demonstrated that the c-jun and
      nNOS protein were constantly expressed in PC12 cells. The cell viability of
      differentiated PC12 cells were significantly inhibited by treatment with 200 and
      400 umol/l 7-NI, and the expression levels of the nNOS protein were significantly
      inhibited by treatment with 200 umol/l 7-NI. However, 7-NI had no significant
      effect on the protein expression level of c-jun and the total activities of cNOS.
      Based on our previous studies, which revealed that the nNOS gene was a downstream
      signaling molecule of the JNK/c-jun signaling pathway in cultured neurons, the
      expression of nNOS downstream was able to be regulated by c-jun which was the
      upstream molecule. Therefore, these results indicated that the association
      between them involved up and downregulation instead of crosstalk.

PMID- 25069403
TI  - Synthesis of 1-indanols and 1-indanamines by intramolecular palladium(0)
      catalyzed C(sp3)-H arylation: impact of conformational effects.
AB  - A range of valuable 1-indanols and 1-indanamines containing a tertiary C1 atom
      were synthesized by intramolecular palladium(0)-catalyzed C(sp(3))-H arylation,
      despite unfavorable steric interactions. The efficiency of the reaction was found
      to correlate with the degree of substitution at C2, as expected from the Thorpe
      Ingold effect. Additionally, the nature of the heteroatomic substituent at C1 had
      a marked influence on the diastereoselectivity at C1 and C2; indeed, 1-indanols
      and 1-indanamines were obtained with the opposite relative configuration.
      Analysis of the X-ray and DFT-optimized structures of the corresponding reactive
      intermediates provided useful insights into the subtle conformational effects
      induced by these substituents.

PMID- 25069404
TI  - Multiresidue determination of ten nonsteroidal anti-inflammatory drugs in bovine,
      porcine, and chicken liver tissues by HPLC-MS/MS.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the group of drugs having the
      therapeutic efficacy of analgesic and antipyretic. To detect health-threatening
      residues of NSAIDs, a fast and easy multiresidue method based on liquid
      chromatography tandem mass spectrometry (LC-MS/MS) was described. Ten NSAIDs were
      extracted from the tissues using 2 mL of acetonitrile and 0.1 mL of 2 mM ammonium
      formate in distilled water. After clean-up using C18 sorbent, it was evaporated
      under nitrogen, reconstituted with 1 mL distilled water and analyzed by LC-MS/MS.
      The method was validated based on guideline for residue testing laboratory.
      Furthermore, the method has also been applied successfully to detect ten NSAIDs
      from bovine, porcine, and chicken liver tissues. In a total of 315 liver samples
      tested, acetylic salicylic acid was detected from 28 porcine and 2 chicken liver
      tissues at levels of 13 ~ 576 and 50 ~ 53 ng/g, respectively. Subsequently,
      paracetamol was detected in 15 porcine liver tissues with a detection levels of
      28 ~ 381 ng/g. Phenylbutazone and its metabolite, oxyphenylbutazone, were
      detected at 247 and 15 ng/g range in one of the bovine liver tissue,
      respectively.

PMID- 25069405
TI  - Purification, gene cloning, and characterization of a novel halohydrin
      dehalogenase from Agromyces mediolanus ZJB120203.
AB  - A novel halohydrin dehalogenase (HHDH), catalyzing the transformation of 1,3
      dichloro-2-propanol (1,3-DCP) to epichlorohydrin (ECH), was purified from
      Agromyces mediolanus ZJB120203. The molecular mass of the enzyme was estimated to
      be 28 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). A 735-bp nucleotide fragment was obtained based on the N-terminal and
      internal amino acid sequences of the purified HHDH. The gene codes a protein
      sequence with 244 amino acid residues, and the protein sequence shows high
      similarity to Hhe AAD2 (HHDH from Arthrobacter sp. AD2), defined as Hhe AAm,
      which is the seventh reported HHDH. Expression of Hhe AAm was carried out in
      Escherichia coli and purification was performed by nickel-affinity
      chromatography. The recombinant HheAAm possessed an optimal pH of 8.5 and an
      optimal temperature of 50  degrees C and manifested a K m of 4.58 mM and a V max
      of 3.84 MUmol/min(/)mg. The activity of Hhe AAm was not significantly affected by
      metal ions such as Zn(2+), Ca(2+), Cu(2+), and EDTA, but was strongly inhibited
      by Hg(2+) and Ag(+). In particular, the Hhe AAm exhibits an enantioselectivity
      for the conversion of prochiral 1,3-DCP to (S)-ECH. The applications of the Hhe
      AAm as a catalyst for asymmetric synthesis are promising.

PMID- 25069406
TI  - Malaria control strategies in French armed forces.
AB  - Each year, 40,000 French soldiers deploy or travel through malaria-endemic areas.
      Despite the effective control measures that were successively implemented,
      malaria remains a public health concern in French armed forces with several
      important outbreaks and one lethal case every two years. This article describes
      the malaria control strategy in French armed forces which is based on three
      combined strategies: i) Anopheles vector control to prevent infection with the
      implementation of personal protection against vectors (PPAV) adapted to the field
      living conditions of the troops. ii) Chemoprophylaxis (CP) to prevent the disease
      based on prescription of effective and well tolerated doxycycline. iii)
      Management of cases through early diagnosis and appropriate treatment to prevent
      death. In isolated conditions in endemic areas, rapid diagnosis tests (RDT) are
      used as first-line tests by military doctors. Treatment of uncomplicated
      Plasmodium falciparum (P. falciparum) malaria is based either on the piperaquine
      tetraphosphate-dihydroartemisinin association since 2013, or on the atovaquone
      proguanil association. First-line treatment of severe P. falciparum malaria is
      based on IV artesunate. These measures are associated with constant education of
      the military, epidemiological surveillance of malaria cases and monitoring of
      parasite chemosensitivity. 

PMID- 25069407
TI  - Culinary delights and travel? A review of zoonotic cestodiases and
      metacestodiases.
AB  - Due to increased globalization, food-borne parasitic infections are becoming more
      prevalent worldwide, including in countries where these parasites and parasitic
      diseases had previously been well controlled or eradicated. Improved sanitation,
      health education, and establishment of appropriate food safety mechanisms can go
      a long way towards the control of many these infections. However, food-borne
      parasitic infections are still common diseases in developing countries,
      especially in rural areas. As many of today's travelers are looking to explore
      more distant locations and partake in the local cuisine, they may be at greater
      risk of acquiring a food-borne parasitic infection, including those caused by a
      number of adult and larval tapeworms. This review discusses fish and meat-borne
      tapeworms and zoonotic metacestodiases of public health importance to both
      developing and developed countries, with a focus on infection prevention in
      travelers. 

PMID- 25069408
TI  - Multiplex pyrosequencing method to determine CYP2C9*3, VKORC1*2, and CYP4F2*3
      polymorphisms simultaneously: its application to a Korean population and
      comparisons with other ethnic groups.
AB  - Warfarin is an anticoagulant that is difficult to administer because of the wide
      variation in dose requirements to achieve a therapeutic effect. CYP2C9, VKROC1,
      and CYP4F2 play important roles in warfarin metabolism, and their genetic
      polymorphisms are related to the variability in dose determination. In this study
      we describe a new multiplex pyrosequencing method to identify CYP2C9*3
      (rs1057910), VKORC1*2 (rs9923231), and CYP4F2*3 (rs2108661) simultaneously. A
      multiplex pyrosequencing method to simultaneously detect CYP2C9*3, VKORC1*2, and
      CYP4F2*3 alleles was designed. We assessed the allele frequencies of the
      polymorphisms in 250 Korean subjects using the multiplex pyrosequencing method.
      The results showed 100 % concordance between single and multiplex pyrosequencing
      methods, and the polymorphisms identified by pyrosequencing were also validated
      with the direct sequencing method. The allele frequencies of these polymorphisms
      in this population were as follows: 0.040 for CYP2C9*3, 0.918 for VKORC1*2, and
      0.416 for CYP4F2*3. Although the allele frequencies of the CYP2C9*3 and VKROC1*2
      were comparable to those in Japanese and Chinese populations, their frequencies
      in this Korean population differed from those in other ethnic groups; the
      CYP4F2*3 frequency was the highest among other ethnic populations including
      Chinese and Japanese populations. The pyrosequencing methods developed were rapid
      and reliable for detecting CYP2C9*3, VKORC1*2, and CYP4F2*3. Large ethnic
      differences in the frequency of these genetic polymorphisms were noted among
      ethnic groups. CYP4F2*3 exhibited its highest allele frequency among other ethnic
      populations compared to that in a Korean population. 

PMID- 25069409
TI  - Monopyrrolotetrathiafulvalene-succinamide conjugates and their TCNQ charge
      transfer complex based supramolecular gels with multiple stimulus responsiveness.
AB  - A series of monopyrrolotetrathiafulvalene-succinamide conjugates and their
      7,7,8,8-tetracyano-p-quinodimethane (TCNQ) charge transfer (CT) complexes have
      been synthesized and investigated as new low-molecular mass organogelators. The
      gelation capability of these conjugates is highly dependent on the length of the
      alkyl chain of the terminal amide. Thus, only the short alkyl chain derivatives
      and could efficiently gelate cyclohexane and methylcyclohexane (MCH).
      Surprisingly, these gelators react with TCNQ to form stable CT complex gels in
      both cyclohexane and MCH. The FE-SEM images of the native gels reveal the
      characteristic gelation morphologies of microporous or fibrous structures,
      whereas the morphologies of CT complex gels show the fibrillar and globular
      aggregates in cyclohexane and MCH, respectively. SAXS study of the native gel and
      the CT complex gel of in cyclohexane suggests that the molecules maintain
      rectangular and hexagonal columnar molecular packing models in the gel phase,
      respectively. The native gels undergo a reversible gel-sol phase transition upon
      exposure to external stimuli, such as temperature and chemical
      oxidation/reduction. Alternatively, the corresponding CT complex gels exhibit a
      complicated response to external stimuli. Chemical oxidation by I2 results in the
      destruction of the gel state. However, neither Fe(3+) nor Cu(2+) can induce the
      collapse of the gel phase. Interestingly, all the gels show an irreversible gel
      sol transition on successively triggering with trifluoroacetic acid and
      triethylamine. The reformation of the gel from the sol state is achieved just by
      the addition of water, showing the phase-selective gelation of the solvents from
      their mixtures with water. 

PMID- 25069410
TI  - Combining and benchmarking methods of foetal ECG extraction without maternal or
      scalp electrode data.
AB  - Despite significant advances in adult clinical electrocardiography (ECG) signal
      processing techniques and the power of digital processors, the analysis of non
      invasive foetal ECG (NI-FECG) is still in its infancy. The Physionet/Computing in
      Cardiology Challenge 2013 addresses some of these limitations by making a set of
      FECG data publicly available to the scientific community for evaluation of signal
      processing techniques.The abdominal ECG signals were first preprocessed with a
      band-pass filter in order to remove higher frequencies and baseline wander. A
      notch filter to remove power interferences at 50 Hz or 60 Hz was applied if
      required. The signals were then normalized before applying various source
      separation techniques to cancel the maternal ECG. These techniques included:
      template subtraction, principal/independent component analysis, extended Kalman
      filter and a combination of a subset of these methods (FUSE method). Foetal QRS
      detection was performed on all residuals using a Pan and Tompkins QRS detector
      and the residual channel with the smoothest foetal heart rate time series was
      selected.The FUSE algorithm performed better than all the individual methods on
      the training data set. On the validation and test sets, the best Challenge scores
      obtained were E1 = 179.44, E2 = 20.79, E3 = 153.07, E4 = 29.62 and E5 = 4.67 for
      events 1-5 respectively using the FUSE method. These were the best Challenge
      scores for E1 and E2 and third and second best Challenge scores for E3, E4 and E5
      out of the 53 international teams that entered the Challenge. The results
      demonstrated that existing standard approaches for foetal heart rate estimation
      can be improved by fusing estimators together. We provide open source code to
      enable benchmarking for each of the standard approaches described. 

PMID- 25069411
TI  - Simultaneous determination of aflatoxins B1, B2, G1, G2 in Fructus Bruceae by
      high-performance liquid chromatography with online postcolumn photochemical
      derivatization.
AB  - A simple, reliable, and highly sensitive method for the simultaneous
      determination of aflatoxin B1 , B2 , G1 , G2 in Fructus Bruceae was developed
      using high-performance liquid chromatography coupled to online postcolumn
      photochemical derivatization and fluorescence detection. Aflatoxins were first
      extracted by a methanol/water mixture and then cleaned up with an AflaTestTM
      immunoaffinity column. Different clean-up and derivatization methods were
      compared and optimized. The established method was extensively validated to show
      satisfactory performance of linearity (R(2) >= 0.9997), recovery (74.3-100.8%),
      and precision (RSDs <= 2.8%) for the investigated aflatoxins. This proposed
      method was also applied to 11 F. Bruceae samples and the results showed that 10
      out of 11 were contaminated with aflatoxins ranging from 0.26 to 27.52 MUg/kg and
      the occurrence of aflatoxin B1 , the most toxic one, was as high as 91% in all
      the samples, highlighting the severe contamination and the necessity to set legal
      limits for aflatoxins in F. Bruceae. 

PMID- 25069413
TI  - Human papillomavirus testing for primary cervical cancer screening: is it time to
      abandon Papanicolaou testing?

PMID- 25069412
TI  - Expression of adrenergic and cholinergic receptors in murine renal intercalated
      cells.
AB  - Neurons influence renal function and help to regulate fluid homeostasis, blood
      pressure and ion excretion. Intercalated cells (ICCs) are distributed throughout
      the renal collecting ducts and help regulate acid/base equilibration. Because
      ICCs are located among principal cells, it has been difficult to determine the
      effects that efferent nerve fibers have on this cell population. In this study,
      we examined the expression of neurotransmitter receptors on the murine renal
      epithelial M-1 cell line. We found that M-1 cells express a2 and b2 adrenergic
      receptor mRNA and the b2 receptor protein. Further, b2 receptor-positive cells in
      the murine cortical collecting ducts also express AQP6, indicating that these
      cells are ICCs. M-1 cells were found to express m1, m4 and m5 muscarinic receptor
      mRNAs and the m1 receptor protein. Cells in the collecting ducts also express the
      m1 receptor protein, and some m1-positive cells express AQP6.
      Acetylcholinesterase was detected in cortical collecting duct cells.
      Interestingly, acetylcholinesterase-positive cells neighbored AQP6-positive
      cells, suggesting that principal cells may regulate the availability of
      acetylcholine. In conclusion, our data suggest that ICCs in murine renal
      collecting ducts may be regulated by the adrenergic and cholinergic systems. 

PMID- 25069414
TI  - High mobility group nucleosome-binding family proteins promote astrocyte
      differentiation of neural precursor cells.
AB  - Astrocytes are the most abundant cell type in the mammalian brain and are
      important for the functions of the central nervous system. Although previous
      studies have shown that the STAT signaling pathway or its regulators promote the
      generation of astrocytes from multipotent neural precursor cells (NPCs) in the
      developing mammalian brain, the molecular mechanisms that regulate the astrocytic
      fate decision have still remained largely unclear. Here, we show that the high
      mobility group nucleosome-binding (HMGN) family proteins, HMGN1, 2, and 3,
      promote astrocyte differentiation of NPCs during brain development. HMGN proteins
      were expressed in NPCs, Sox9(+) glial progenitors, and GFAP(+) astrocytes in
      perinatal and adult brains. Forced expression of either HMGN1, 2, or 3 in NPCs in
      cultures or in the late embryonic neocortex increased the generation of
      astrocytes at the expense of neurons. Conversely, knockdown of either HMGN1, 2,
      or 3 in NPCs suppressed astrocyte differentiation and promoted neuronal
      differentiation. Importantly, overexpression of HMGN proteins did not induce the
      phosphorylation of STAT3 or activate STAT reporter genes. In addition, HMGN
      family proteins did not enhance DNA demethylation and acetylation of histone H3
      around the STAT-binding site of the gfap promoter. Moreover, knockdown of HMGN
      family proteins significantly reduced astrocyte differentiation induced by
      gliogenic signal ciliary neurotrophic factor, which activates the JAK-STAT
      pathway. Therefore, we propose that HMGN family proteins are novel chromatin
      regulatory factors that control astrocyte fate decision/differentiation in
      parallel with or downstream of the JAK-STAT pathway through modulation of the
      responsiveness to gliogenic signals.

PMID- 25069415
TI  - The clinical presentation and early outcomes of necrotizing fasciitis in a
      Ugandan Tertiary Hospital--a prospective study.
AB  - BACKGROUND: Necrotizing fasciitis is an infectious process characterized by
      rapidly progressing necrosis of superficial fascia and subcutaneous tissue with
      subsequent necrosis of overlying skin.Necrotizing fasciitis is a rare but fatal
      infection. The worldwide incidence is at 0.4 per 100,000. Mortality is up to 80%
      with no intervention, and 30-50% with intervention. Delay in intervention is
      associated with poor outcome. The risk factors for necrotizing fasciitis are
      diabetes mellitus, HIV, malignancy, illicit drug use, malnutrition among
      others.The aim of this study was to describe the clinical presentation and early
      outcomes of necrotizing fasciitis amongst Ugandan patients. METHODS: A
      prospective descriptive case series study conducted at Mulago National Referral
      and Teaching hospital from 5th January to 30th April 2011. Patients with
      necrotizing fasciitis were consecutively recruited after clinical evaluation,
      laboratory and microbiological tests were performed. Aggressive debridement was
      done and broad-spectrum antibiotics administered. Patients were followed up on
      surgical wards. Ethical approval was obtained. RESULTS: Thirty five patients were
      recruited over a 4 months period. More males were affected with, M: F 3:1. The 20
      40 years age group was most affected. Attainment of healthy granulation tissue
      took 19 days on average. Mortality rate was 14% (5/35). Limbs were the most
      affected body parts 20/35 (57%), the scrotum and perineum (23%). Among infants
      the scalp was the most affected. Co-morbidities included HIV 8/35 (17%), and DM
      (5%) among others. The commonest organisms were gram negative. Split skin
      grafting was necessary in 74% (26/35) of patients. CONCLUSION: There were a high
      number of patients with necrotizing fasciitis; it was associated with low
      mortality but high morbidity (long hospital stay). There was a high preponderance
      to males and limbs were the more affected body parts.

PMID- 25069416
TI  - Necrotizing Fasciitis Associated with Pregnancy: a Population-Based Cohort Study.
AB  - INTRODUCTION: Necrotizing fasciitis (NF) is a rare complication in pregnant
      women. There have been no population-level data reported to date on its
      epidemiology, clinical features, resource utilization, and outcomes. METHODS:
      This was a retrospective, population-based cohort study, using the Texas
      Inpatient Public Use Data File to identify pregnancy-associated hospitalizations
      for the years 2001-2010. Hospitalizations with a diagnosis of NF were then
      identified using the International Classification of Diseases, Ninth Revision,
      Clinical Modification code 728.86. Denominator data for incidence estimates were
      derived from the Texas Center for Health Statistics reports of live births,
      abortions and fetal deaths, and previously reported population-based, age
      specific linkage data on miscarriage, and were used to estimate the annual total
      number of pregnancies (TEP). The incidence of pregnancy-associated NF (PANF),
      hospitalization type, clinical features, resource utilization and outcomes were
      examined. RESULTS: There were 4,060,201 pregnancy-associated hospitalizations and
      148 PANF hospitalizations during study period. Postpartum hospitalizations
      accounted for 82.4% of all PANF events, and intensive care unit care was required
      in 61.5%. The key trends noted between 2001-2002 and 2009-2010 included rising
      incidence of PANF from 1.1 vs. 3.8 per 100,000 TEP-years (P = 0.0001), chronic
      comorbidities 0% vs. 31.7% (P = 0.0777), and development of organ failure in 9.1%
      vs. 31.7% (P = 0.0302). There was no significant change in total hospital charges
      or hospital length of stay. Three patients (2%) died in the hospital and 55% of
      survivors had routine home discharge. CONCLUSIONS: The present cohort of PANF is
      the largest reported to date. The incidence of PANF rose nearly 3.5-fold over the
      past decade, with most events developing following delivery hospitalization.
      Chronic illness has been increasingly present, along with rising severity of
      illness. The majority of patients required ICU care. Hospital mortality was lower
      than that reported for NF in the general population. The sources of the observed
      findings require further study.

PMID- 25069417
TI  - Dexmedetomidine suppresses interleukin-1beta-induced interleukin-6 synthesis in
      rat glial cells.
AB  - Dexmedetomidine, an alpha2-adrenoceptor agonist, is used as a sedative medication
      for criticalyl ill patients and is known to exert neuroprotective effects by
      direct action on neurons and indirect action on neurons through astrocytes.
      Interleukin (IL)-6 plays a key role in neuroinflammation, which accompanies
      infection, traumatic brain injury, ischemia, neurodegenerative disorders, as both
      a pro-inflammatory cytokine and an anti-inflammatory cytokine. Dexmedetomidine
      suppresses immune function. However, the effects of dexmedetomidine on cytokine
      synthesis in the central nervous system (CNS) remain elusive. We previously
      reported that IL-1beta stimulates IL-6 synthesis in the rat C6 glioma cell line
      through the phosphorylation of p38 mitogen-activated protein (MAP) kinase, stress
      activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and IkappaB. In the
      present study, we investigated the effects of dexmedetomidine on the IL-1beta
      induced IL-6 synthesis in C6 cells. Dexmedetomidine inhibited the IL-1beta
      stimulated IL-6 release and mRNA expression in C6 cells. 8-Bromo-adenosine-3',5'
      cyclic monophosphate, but not 8-bromo-guanosine 3',5'-cyclic monophosphate,
      significantly enhanced the IL-1beta-induced IL-6 release and mRNA expression.
      However, dexmedetomidine failed to affect cAMP accumulation in the cells treated
      with IL-1beta or forskolin, an activator of adenylyl cyclase. Yohimbine, an
      alpha2-adrenoceptor antagonist, did not reverse the suppressive effects of
      dexmedetomidine on the IL-1beta-induced IL-6 release. Dexmedetomidine did not
      affect the IL-1beta-induced phosphorylation of p38 MAP kinase, SAPK/JNK, IkappaB,
      nuclear factor (NF)-kappaB or c-Jun. Our findings strongly suggest that
      dexmedetomidine inhibits the IL-1beta-induced IL-6 synthesis independently of the
      adenylyl cyclase-cAMP pathway through alpha2-adrenoceptors in C6 glioma cells. It
      is possible that dexmedetomidine may affect the immune system in the CNS by
      regulating the production of IL-6. 

PMID- 25069418
TI  - Recovery resources and psychiatric severity among persons with substance use
      disorders.
AB  - A comparative analysis of recovery resources (abstinence social support,
      abstinence self-efficacy) was conducted among two groups exiting inpatient
      treatment for substance use disorders: persons with psychiatric comorbid
      substance use disorders and persons with substance use disorders. Both groups
      reported comparable levels of abstinence social support, but this resource was
      not significantly related to substance use among persons with psychiatric
      comorbid substance use disorders. Although abstinence self-efficacy was
      significantly related to substance use, persons with psychiatric comorbid
      substance use disorders reported significantly lower levels of abstinence self
      efficacy than persons with substance use disorders. Findings suggest that persons
      with psychiatric comorbid substance use disorders exit alcohol/drug treatment
      with lower levels of abstinence self-efficacy compared to their substance use
      disorder peers. 

PMID- 25069419
TI  - Suicide risk and mental health co-morbidities in a probationer population.
AB  - Mental health problems are disproportionately represented in the community
      corrections system with limited information on the epidemiology of mental health
      and correlated factors such as suicide among probationers. This study recruited
      2,077 probationers who completed screeners for mental health and substance
      disorders and suicide risk. Results found 13% of probationers were at high risk
      of suicide. Those who screened positive for a mental health condition were
      between 2 and 8 times more likely to screen positive for suicide risk. Allocation
      of additional resources to mental health in the criminal justice system and to
      effectively coordinate existing mental health services is needed.

PMID- 25069420
TI  - A parental tool to screen for posttraumatic stress in children: first
      psychometric results.
AB  - The Children's Revised Impact of Event Scale (CRIES-13) is a brief self-report
      measure designed to screen children for posttraumatic stress disorder (PTSD).
      This study investigates the psychometric properties of a Dutch version of the
      CRIES-13-parent version and evaluates its correlation with the child version. A
      sample of 59 trauma-exposed children (8 years-18 years) and their parents
      completed an assessment including the CRIES-13 (child/parent version) along with
      the Anxiety Disorders Interview Schedule for DSM-IV: Parent version. Results
      demonstrated good internal consistency (alpha = .87) with acceptable values for
      the 3 subscales. A strong correlation (r = .73) with another measure of PTSD and
      lower correlations with a behavioral measure (r = .15 to .38) were found,
      confirming the convergent/divergent validity. A cutoff score >= 31 emerged as the
      best balance between sensitivity and specificity, and correctly classified 83.6%
      of all children as having a diagnosis of PTSD. This study provides support for
      the reliability and validity of the CRIES-13-parent version as a screening
      measure for posttraumatic stress in children. 

PMID- 25069421
TI  - Tumor VEGF expression correlates with tumor stage and identifies prognostically
      different groups in patients with clear cell renal cell carcinoma.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) is a potent inducer of
      tumor angiogenesis and represents the key element in the pathogenesis of clear
      cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the
      use of tumor VEGF expression as a parameter to identify tumor stage and
      prognostically different patient groups. METHODS AND MATERIALS: We
      retrospectively collected clinical data of 137 patients treated with partial or
      radical nephrectomy at our institutions for organ-confined, locally advanced, and
      metastatic ccRCCs between 1984 and 2013. Tumor cell VEGF immunohistochemical
      expression was compared with pathological and clinical features including age,
      sex, tumor stage, and Fuhrman grade. Comparison of VEGF expression levels between
      tumor stages was performed via Kruskal-Wallis nonparametric test. Survival
      analysis was conducted via Kaplan-Meier product-limit method, and Mantel-Haenszel
      log-rank test was employed to compare survival among groups. RESULTS: Median age
      at diagnosis was 61 years (range: 33-85 y). Tumor stage was pT1N0M0 in 67
      patients (49%), pT2N0M0 in 5 (4%), and pT3N0M0 in 25 (18%), while 40 patients
      (29%) had metastatic tumors at diagnosis. Fuhrman nuclear grade was G1 in 22
      patients (16%), G2 in 60 (44%), G3 in 33 (24%), G4 in 13 patients (9%), and
      unknown in 9 patients. Tumor VEGF was differentially expressed among different
      stages (P<0.001) and in low (G1-2) and high (G3-4) Fuhrman grade tumors
      (P<0.001). No significant differences were found when stratifying by sex (P =
      0.06) or age (P = 0.29). Median overall survival (OS) from partial or radical
      nephrectomy was 161 months (range: 1-366). We observed a significantly longer OS
      in patients with low (<25%) vs. high (>25%) VEGF expression levels (median OS 206
      vs. 65 mo, P<0.001). CONCLUSIONS: Our data show that tumor cell VEGF expression
      is significantly associated with tumor stage and Fuhrman grade and is able to
      predict patient outcome, suggesting a potential use of this parameter in
      identifying prognostically different patients with ccRCC.

PMID- 25069422
TI  - Pericardial ectopic thymoma presenting with cardiac tamponade: report of a case.
AB  - Ectopic thymoma arising from organs other than the thymus, such as the neck,
      trachea, thyroid, lung and pericardium, is rare. To date, there have been only
      seven other cases of pericardial thymoma reported in the English literature. We
      herein report a case of pericardial ectopic thymoma that presented with cardiac
      tamponade. A 72-year-old Japanese male noticed body weight gain and leg edema.
      Chest computed tomography (CT) revealed pericardial effusion and an irregularly
      shaped mass in the pericardial space compressing the right atrium. He was
      considered to have cardiac tamponade due to a paracardiac tumor that developed
      following acute cardiac failure. The intraoperative frozen diagnosis was thymoma.
      Pericardectomy of the thickened pericardium, tumorectomy and thymectomy via a
      median sternotomy were performed. The final pathological diagnosis was
      pericardial ectopic thymoma associated with constrictive pericarditis. The
      differential diagnosis and complete resection of mediastinal tumors such as this
      rare case of thymoma are important to obtain a better prognosis, as patients with
      such tumors often present in a state of shock. 

PMID- 25069423
TI  - Primary malignant melanoma of the thymus: report of a case.
AB  - A 61-year-old male was admitted to our hospital complaining of bloody sputum. A
      chest roentgenogram revealed a clearly demarcated mass located in the anterior
      mediastinum. Positron emission tomography revealed abnormal accumulation of (18)F
      fluorodeoxy glucose only in the anterior mediastinal tumor. A computed tomography
      guided needle aspiration biopsy was performed, and the tumor was diagnosed as a
      malignant melanoma. Although the skin, eyeballs, oral cavity, nasal cavity, etc.,
      were closely evaluated, no other lesion of malignant melanoma was detected except
      the mediastinal tumor. Hence, this tumor was diagnosed as a primary malignant
      melanoma. We performed total thymectomy, including the tumor, and combined
      resection of the adhesive bilateral lungs, pericardium and left brachiocephalic
      vein. Because the tumor was histologically surrounded by thymus tissue, we
      diagnosed it as a primary mediastinal malignant melanoma that originated in the
      thymus. Although the patient's postoperative course was uneventful, he complained
      of back pain 5 months after the operation. Multiple bone metastases were found,
      and he received chemotherapy and radiotherapy, and is currently alive with
      disease 14 months after the primary treatment.

PMID- 25069424
TI  - Paenilarvins: Iturin family lipopeptides from the honey bee pathogen
      Paenibacillus larvae.
AB  - The bacterium Paenibacillus larvae has been extensively studied as it is an
      appalling honey bee pathogen. In the present work, we screened crude extracts
      derived from fermentations of P. larvae genotypes ERIC I and II for antimicrobial
      activity, following the detection of four putative secondary metabolite gene
      clusters that show high sequence homology to known biosynthetic gene clusters for
      the biosynthesis of antibiotics. Low molecular weight metabolites produced by P.
      larvae have recently been shown to have toxic effects on honey bee larvae.
      Moreover, a novel tripeptide, sevadicin, was recently characterized from
      laboratory cultures of P. larvae. In this study, paenilarvins, which are iturinic
      lipopeptides exhibiting strong antifungal activities, were obtained by bioassay
      guided fractionation from cultures of P. larvae, genotype ERIC II. Their
      molecular structures were determined by extensive 2D NMR spectroscopy, high
      resolution mass spectrometry, and other methods. Paenilarvins are the first
      antifungal secondary metabolites to be identified from P. larvae. In preliminary
      experiments, these lipopeptides also affected honey bee larvae and might thus
      play a role in P. larvae survival and pathogenesis. However, further studies are
      needed to investigate their function. 

PMID- 25069426
TI  - Epidemiology of osteoporotic hip fractures in Western Romania.
AB  - PURPOSE: Fragility hip fractures represent a major health and social burden. To
      date, there are no reports regarding mortality and factors that influence
      outcomes after osteoporotic hip fractures in Romania. MATERIAL AND METHODS: The
      electronic database of the largest healthcare provider in the western part of the
      country was searched for hip fracture admissions between 2008 and 2012. Inclusion
      criteria were age over 55 and the diagnosis of intra or extracapsular fractures,
      corresponding to ICD-10 S72.0 and S72.1 codes, respectively. RESULTS: A total of
      1,866 patients met the criteria and were selected for data analysis. The gain in
      rates and crude numbers was caused mainly by a rise of fractures in males. The
      opposite is seen for the female-to-male ratio. Even though the mean age steadily
      increased for a total of 1.5 over a five-year period the patients are still
      younger than the European averages, which might explain the slightly better one
      year survival. The age-gender adjusted hip fracture incidence increased
      dramatically with age, especially in women. The relative risk of dying in the
      first year is 1.359 times higher if the fracture is extracapsular (95% CI 1.12
      1.65). In total, 21.1% of all patients die by one year after the fracture. This
      was drastically reduced for the following years. The survival function is
      significantly dependent on age group, level of fracture and time from hospital
      admission until surgery (p < 0.001). CONCLUSIONS: Increased age, extracapsular
      fractures and delayed surgery have worse outcomes. Regarding gender, even if not
      significant at the 0.05 level, probability of survival for females is higher for
      all time intervals. Updated, regional studies could be used in patient management
      to improve outcomes whilst decreasing costs.

PMID- 25069427
TI  - Neglected ununited tibial eminence fractures in the skeletally immature:
      arthroscopic management.
AB  - PURPOSE: The purpose of this study was to prospectively evaluate outcomes of
      arthroscopic management of neglected ununited tibial eminence fractures in
      skeletally immature patients. METHODS: The study was conducted and cases
      performed by two surgeons from two centres as a prospective case series of 13
      patients with neglected ununited tibial eminence fractures: nine were girls and
      four were boys; ten were right knees and three were left. The average age at
      surgery was ten [standard deviation (SD) 2.6] years. Average follow-up was 10.8
      (SD 6.8) months. Primary outcome measures used for evaluation were the Objective
      International Knee Documentation Committee Score (IKDC), subjective IKDC and
      modified Lysholm knee score. Secondary outcome measures were visual analogue
      scales (VAS) for pain and patient satisfaction. RESULTS: Twelve patients had
      grade A objective IKDC score and one patient had grade B. Average subjective IKDC
      score was 80.5 (SD 16.7). Average modified Lysholm score was 91.2 (SD 8.9).
      Average VAS for operation satisfaction was 9.6 (SD 0.5) and for pain was 0.4 (SD
      0.5). All patients showed radiological union and anatomical reduction at an
      average of 12.4 weeks postoperatively. At follow-up, all 13 patients showed
      complete range of motion (ROM). Eleven patients had negative Lachman, anterior
      drawer and pivot-shift tests, while two patients had grade 1 positive Lachman and
      negative anterior drawer and pivot-shift tests. No patient had complained of
      instability. CONCLUSION: Neglected ununited tibial eminence fractures in
      skeletally immature patients achieve good functional outcome results when treated
      with arthroscopic reduction and internal fixation using sutures.

PMID- 25069429
TI  - New insights into the by-product fatigue mechanism of the photo-induced ring
      opening in diarylethenes.
AB  - The photochromic properties of diarylethenes, some of the most studied class of
      molecular switches, are known to be controlled by non-adiabatic decay at a
      conical intersection seam. Nevertheless, as their fatigue-reaction mechanism -
      leading to non-photochromic products - is yet to be understood, we investigate
      the photo-chemical formation of the so-called by-product isomer using three
      complementary computational methods (MMVB, CASSCF and CASPT2) on three model
      systems of increasing complexity. We show that for the ring-opening reaction a
      transition state on S1(2A) involving bond breaking of the penta-ring leads to a
      low energy S1(2A)/S0(1A) conical intersection seam, which lies above one of the
      transition states leading to the by-product isomer on the ground state.
      Therefore, radiationless decay and subsequent side-product formation can take
      place explaining the photo-degradation responsible for the by-product generation
      in diarylethene-type molecules. The effect of dynamic electron correlation and
      the possible role of inter-system crossing along the penta-ring opening
      coordinate are discussed as well. 

PMID- 25069428
TI  - Augmented cellular uptake of nanoparticles using tea catechins: effect of surface
      modification on nanoparticle-cell interaction.
AB  - Nanoparticles may serve as carriers in targeted therapeutics; interaction of the
      nanoparticles with a biological system may determine their targeting effects and
      therapeutic efficacy. Epigallocatechin-3-gallate (EGCG), a major component of tea
      catechins, has been conjugated with nanoparticles and tested as an anticancer
      agent. We investigated whether EGCG may enhance nanoparticle uptake by tumor
      cells. Cellular uptake of a dextran-coated magnetic nanoparticle (MNP) was
      determined by confocal microscopy, flow cytometry or a potassium thiocyanate
      colorimetric method. We demonstrated that EGCG greatly enhanced interaction
      and/or internalization of MNPs (with or without polyethylene glycol) by glioma
      cells, but not vascular endothelial cells. The enhancing effects are both time-
      and concentration-dependent. Such effects may be induced by a simple mix of MNPs
      with EGCG at a concentration as low as 1-3 MUM, which increased MNP uptake 2- to
      7-fold. In addition, application of magnetic force further potentiated MNP
      uptake, suggesting a synergetic effect of EGCG and magnetic force. Because the
      effects of EGCG were preserved at 4  degrees C, but not when EGCG was removed
      from the culture medium prior to addition of MNPs, a direct interaction of EGCG
      and MNPs was implicated. Use of an MNP-EGCG composite produced by adsorption of
      EGCG and magnetic separation also led to an enhanced uptake. The results reveal a
      novel interaction of a food component and nanocarrier system, which may be
      potentially amenable to magnetofection, cell labeling/tracing, and targeted
      therapeutics. 

PMID- 25069430
TI  - Parametric mapping and quantitative analysis of the human calvarium.
AB  - In this paper we report how thickness and density vary over the calvarium region
      of a collection of human skulls. Most previous reports involved a limited number
      of skulls, with a limited number of measurement sites per skull, so data in the
      literature are sparse. We collected computer tomography (CT) scans of 51 ex vivo
      human calvaria, and analyzed these in silico using over 2000 measurement sites
      per skull. Thickness and density were calculated at these sites, for the three
      skull layers separately and combined, and were mapped parametrically onto the
      skull surfaces to examine the spatial variations per skull. These were found to
      be highly variable, and unique descriptors of the individual skulls. Of the three
      skull layers, the thickness of the inner cortical layer was found to be the most
      variable, while the least variable was the outer cortical density. 

PMID- 25069431
TI  - Latent classes of nonresponders, rapid responders, and gradual responders in
      depressed outpatients receiving antidepressant medication and psychotherapy.
AB  - BACKGROUND: We used growth mixture modeling (GMM) to identify subsets of patients
      with qualitatively distinct symptom trajectories resulting from treatment.
      Existing studies have focused on 12-week antidepressant trials. We used data from
      a concurrent antidepressant and psychotherapy trial over a 6-month period.
      METHOD: Eight hundred twenty-one patients were randomized to receive either
      fluoxetine or tianepine and received cognitive-behavioral therapy, supportive
      therapy, or psychodynamic therapy. Patients completed the Montgomery-Asberg
      depression rating scale (MADRS) at the 0, 1, 3, and 6-month periods. Patients
      also completed measures of dysfunctional attitudes, functioning, and personality.
      GMM was conducted using MADRS scores and the number of growth classes to be
      retained was based on the Bayesian information criterion. RESULTS: Criteria
      supported the presence of four distinct latent growth classes representing
      gradual responders of high severity (42% of sample), gradual responders of
      moderate severity (31%), nonresponders (15%), and rapid responders (11%). Initial
      severity, greater use of emotional coping strategies, less use of avoidance
      coping strategies, introversion, and less emotional stability predicted
      nonresponder status. Growth classes were not associated with different treatments
      or with proportion of dropouts. CONCLUSIONS: The longer time period used in this
      study highlights potential overestimates of nonresponders in previous research
      and the need for continued assessments. Our findings demonstrate distinct growth
      trajectories that are independent of treatment modality and generalizable to most
      psychotherapy patients. The correlates of class membership provide directions for
      future studies, which can refine methods to predict likely nonresponders as a
      means to facilitate personalized treatments.

PMID- 25069432
TI  - Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and
      axons in 3-D.

PMID- 25069433
TI  - 3D-printed chip for detection of methicillin-resistant Staphylococcus aureus
      labeled with gold nanoparticles.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen
      occurring not only in hospitals but also in foodstuff. Currently, discussions on
      the issue of the increasing resistance, and timely and rapid diagnostic of
      resistance strains have become more frequent and sought. Therefore, the aim of
      this study was to design an effective platform for DNA isolation from different
      species of microorganisms as well as the amplification of mecA gene that encodes
      the resistance to beta-lactam antibiotic formation and is contained in MRSA. For
      this purpose, we fabricated 3D-printed chip that was suitable for bacterial
      cultivation, DNA isolation, PCR, and detection of amplified gene using gold
      nanoparticle (AuNP) probes as an indicator of MRSA. Confirmation of the MRSA
      presence in the samples was based on a specific interaction between mecA gene
      with the AuNP probes and a colorimetric detection, which utilized the noncross
      linking aggregation phenomenon of DNA-functionalized AuNPs. To test the whole
      system, we analyzed several real refractive indexes, in which two of them were
      positively scanned to find the presence of mecA gene. The aggregation of AuNP
      probes were reflected by 75% decrease of absorbance (lambda = 530 nm) and change
      in AuNPs size from 3 +/- 0.05 to 4 +/- 0.05 nm (n = 5). We provide the one-step
      identification of mecA gene using the unique platform that employs the rapid, low
      cost, and easy-to-use colorimetric method for MRSA detection in various samples. 

PMID- 25069434
TI  - Triple assessment of sentinel lymph node metastasis in early breast cancer using
      preoperative CTLG, intraoperative fluorescence navigation and OSNA.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) became a standard surgical
      procedure for patients with early breast cancer; however, the optimal method of
      sentinel lymph node (SLN) identification remains controversial. The current study
      presents the protocol of our institution for preoperative and intraoperative SLN
      detection. METHODS: Fifty female patients with early breast cancer and clinically
      node-negative axilla were enrolled in this study. All patients underwent
      preoperative CT lymphography (CTLG), intraoperative SLNB using fluorescence
      navigation, intraoperative one-step nucleic acid amplification (OSNA) and
      postoperative hematoxylin and eosin histopathological analysis. Prediction of
      metastasis by CTLG and detection of metastasis by OSNA were compared to results
      of histopathology as standard reference. RESULTS: SLN were identified by
      preoperative CTLG and intraoperative SLNB with fluorescence navigation in all
      patients, the identification rate was 100 %. SLN metastases were detected as
      positive by OSNA in 9 patients (18 %), 4 were (++), 4 were (+) and 1 was (+I).
      SLN metastases were detected as positive by histopathology in 10 patients (20 %).
      The concordance rate between OSNA and permanent sections was 90 %. The negative
      predictive value of CTLG was 80 %. CONCLUSION: Use of CTLG and fluorescence
      navigation made performing SLNB with high accuracy possible in institutions that
      cannot use the radioisotope method. OSNA provided accurate intraoperative method,
      allowing for completion of axillary node dissection during surgery and avoidance
      of second surgical procedure in patients with positive SLNs, thereby reducing
      patient distress and, finally, saving hospital costs.

PMID- 25069435
TI  - [Intracranial hypotension].
AB  - In this review article the clinical manifestations, imaging findings, diagnostic
      and therapeutic approaches for intracranial hypotension are described. The
      typical manifestation, orthostatic headache, may sometimes be masked by atypical
      manifestations including coma, frontotemporal dementia and symptoms associated
      with leptomeningeal hemosiderosis. Spinal and cranial magnetic resonance imaging
      (MRI) findings are not always unequivocal and the diagnostic and therapeutic
      approaches are controversially discussed: Searching for the underlying spinal
      leak(s) of cerebral spinal fluid (CSF) is considered to be unnecessary or done
      with different modalities, such as computed tomography (CT) myelography,
      gadolinium-enhanced myelography and digital subtraction myelography. Various
      treatment approaches including conservative therapy, blind, fluoroscopy-guided
      and CT-guided epidural blood patches, CT-guided fibrin injection and surgery
      exist. 

PMID- 25069436
TI  - [Psychiatry and NS euthanasia. Facts, transgenerational effects and work with the
      relatives in Carinthia/Austria].
AB  - OBJECTIVE: This article describes the current state of research concerning the
      fate of mentally ill people in the psychiatric hospital of Klagenfurt am
      Worthersee during the era of National Socialism (NS). Sterilization based on the
      "Erbgesundheitsgesetz" (genetic health law) deportation to the Castle of Hartheim
      near Linz, transport to Klagenfurt and killing in the departments of the hospital
      are documented. This knowledge is to be given to the relatives. METHOD:
      Encouraged by diverse public work activities relatives of victims of NS
      euthanasia sought contact with the department to discover the fate of relatives.
      Touching meetings with the relatives took place. RESULTS: Since January 2011 the
      contacting relatives, their motives and the meetings have been protocolled and in
      this study an attempt is made to give an initial characterization of these
      people. CONCLUSION: This approach of a reconstructive biographical work together
      with relatives of the victims is presented as a proactive duty of psychiatric
      institutions.

PMID- 25069437
TI  - Surgical techniques for the removal of mandibular wisdom teeth.
AB  - BACKGROUND: The surgical removal of mandibular wisdom teeth is one of the most
      common operations undertaken in oral and maxillofacial surgery. The most common
      indication for surgery is infection about a partially erupted tooth that is
      impacted against bone or soft tissues. Other indications include unrestorable
      caries, pulpal and periapical pathology, fracture of the tooth and cyst
      development, amongst others. Most commonly the benefits of surgical removal of a
      wisdom tooth include alleviation of the symptoms and signs of pericoronitis and
      its potential consequences. However, surgery is frequently associated with
      postoperative pain, swelling and trismus. Less commonly complications include
      infection, including dry socket, trigeminal nerve injuries and rarely fracture of
      the mandible. OBJECTIVES: To compare the relative benefits and risks of different
      techniques for undertaking various aspects or stages of the surgical extraction
      of mandibular wisdom teeth. SEARCH METHODS: We searched the Cochrane Oral Health
      Group's Trials Register (to 21 March 2014), CENTRAL (The Cochrane Library 2014,
      Issue 1), MEDLINE (OVID) (1946 to 21 March 2014) and EMBASE (OVID) (1980 to 21
      March 2014). We searched ClinicalTrials.gov and the WHO International Clinical
      Trials Registry Platform for ongoing trials. There were no restrictions regarding
      language or date of publication in the electronic searches. SELECTION CRITERIA:
      RCTs comparing surgical techniques for removal of mandibular wisdom teeth. DATA
      COLLECTION AND ANALYSIS: Two review authors conducted assessment of relevance,
      risk of bias and data extraction. Study authors were contacted for additional
      information. RRs were used for dichotomous data and MDs for continuous data,
      unless the event rate was very low and Peto ORs were used. The pairing of the
      split-mouth studies was taken into account in the analysis for both dichotomous
      and continuous outcomes, and parallel group and split-mouth studies were combined
      using the generic inverse variance method. Random-effects models were used
      provided there were more than three studies (fixed-effect models otherwise). MAIN
      RESULTS: A total of 35 trials (2569 patients) were included. The interventions
      under consideration fell into seven broad categories, with many comparisons
      including only a small number of trials. Twenty-one of the trials were assessed
      at high risk of bias, the remaining 14 as unclear. The results are described in
      the summary of findings tables.Triangular flaps were associated with a 71%
      reduction in alveolar osteitis at one week (RR 0.29, 95% CI 0.11 to 0.78; three
      trials, moderate quality) and reduction in pain at 24 hours (MD -0.21, 95% CI 
      0.32 to -0.10; two trials, moderate quality) compared with envelope flaps. There
      was no evidence of a difference in overall infection rates, in maximum mouth
      opening or in permanent sensation. However, there was some evidence that residual
      swelling after one week was slightly increased in the triangular flap groups
      compared to envelope flap types (MD 0.66 mm, 95% CI 0.26 to 1.07; two trials, low
      quality). We found no data on temporary sensation, or adverse events.There was
      low quality evidence from two studies, looking at the use of a retractor during
      third molar surgery, to indicate more cases of temporary altered sensation (up to
      one month) when a retractor was used (Peto OR 5.19, 95% CI 1.38 to 19.49; two
      trials, low quality). One study reported that this did not persist for more than
      six months in either group. We found no data for use of a retractor on other
      primary outcomes or adverse effects (including fracture of the mandible).Due to
      the small number of studies, the different comparisons evaluated, the variable
      outcomes reported and the paucity of useful data for all primary outcomes we were
      not able to draw any conclusions concerning bone removal in third molar
      surgery.There was insufficient evidence from single studies of very low quality
      on irrigation method (manual versus mechanical) or irrigation volume (low or
      high) to determine whether there were differences or not for the outcomes of
      alveolar osteitis or postoperative infection. We found no data for any of the
      other primary outcomes.There was insufficient evidence (low to very low quality)
      that any wound closure technique (primary versus secondary) was superior to
      another for the outcomes of alveolar osteitis, postoperative infection or maximum
      mouth opening achieved after seven days, or reactionary bleeding. There was
      evidence that secondary wound closure was associated with reduced pain at 24
      hours (MD 0.79, 95% CI 0.35 to 1.24; four trials, moderate quality) and slightly
      reduced swelling after one week (MD 0.33, 95% CI 0.09 to 0.57; seven trials,
      moderate quality).We found no data on other primary outcomes.There was some
      evidence that the use of a surgical drain was associated with less postoperative
      swelling (MD -0.90, 95% CI -1.62 to -0.19; five trials, moderate quality) and
      greater maximum mouth opening one week after surgery (MD 3.72 mm, 95% CI 2.84 to
      4.59; two trials, moderate quality). There was insufficient evidence from a
      single study (low quality) to determine whether the presence of a drain made any
      difference to pain at 24 hours postoperation. There were no data for the other
      primary outcomes.Although two RCTs compared coronectomy with complete extraction,
      flaws in the design and the unit of analysis of these studies meant that there
      were no reliable data available for inclusion. AUTHORS' CONCLUSIONS: The thirty
      five included trials looked at a range of different surgical techniques. The
      comparisons related to seven broad aspects of the surgical procedures for
      impacted mandibular third molars: type of surgical flap raised, use of
      retractors, techniques for bone removal, wound irrigation, wound closure, wound
      drainage, and complete/incomplete tooth removal. The quality of the body of
      evidence for each of these comparisons was very low to moderate due to the small
      number of trials and patients, and the majority of the trials being at high risk
      of bias (65%) with the remainder at unclear risk of bias.The evidence for making
      changes to surgical practice is therefore limited. However, it is useful to
      describe the state of the research evidence supporting practice so that surgeons
      can make an informed choice in adopting new techniques, or continuing with
      established techniques.

PMID- 25069438
TI  - microRNA aberrations and their role in supporting hematologic malignancies.

PMID- 25069439
TI  - MicroRNAs as main players in the pathogenesis of chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western
      world. The accumulation of mature CD5(+) B-lymphocytes in bone marrow, peripheral
      blood, and lymphoid organs due to decreased apoptosis is a characteristic of this
      malignancy. MicroRNAs (miRNAs) are small noncoding RNAs able to regulate the
      expression of many target genes, including the main apoptosis regulators BCL2 and
      MCL1. miRNAs play key roles in the pathogenesis of CLL, including specific miRNAs
      located at the 13q14 chromosomal region that is often deleted or mutated in
      patients with CLL. In this paper, we review new investigations that underscore
      the significance of miRNAs for CLL pathogenesis.

PMID- 25069440
TI  - The role of miRNAs in plasma cell dyscrasias.
AB  - Plasma cell dyscrasias are a group of related disorders that have in common the
      clonal proliferation of plasma cells with resultant production of a monoclonal
      immunoglobulin that can be detected on serum protein electrophoresis (M-spike).
      This term incorporates the Plasma Cell Neoplasms along with other related
      disorders that are not considered malignant. Comprehensive genomic studies have
      greatly advanced our understanding of the genetic complexity of these diseases in
      recent years, however they continue to be considered incurable with a highly
      heterogeneous phenotype. It is clear that a deeper level of knowledge of the
      biological events underlying the development of these diseases is needed to
      identify new targets and generate effective novel therapies. MicroRNAs (miRNAs),
      which are single strand, 20- nucleotide, non-coding RNAs, are key regulators of
      gene expression and have been reported to exert transcriptional control in
      multiple myeloma and other plasma cell dyscrasias. miRNAs are now recognized to
      play a role in many key areas such as cellular proliferation, differentiation,
      apoptosis and stress response. Substantial advances have been made in recent
      years in terms of our understanding of the biological role of miRNAs in this
      complex and diverse set of disorders, leading to the new information, which is of
      diagnostic and prognostic relevance.

PMID- 25069441
TI  - MicroRNA dysregulation in the myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are heterogeneous clonal disorders of
      ineffective hematopoiesis characterized by limited treatment options and a poor
      prognosis. These poor clinical characteristics stem from a poor understanding of
      the molecular abnormalities that drive disease pathogenesis. MicroRNAs (miRNAs)
      have recently been described to play wide-ranging roles in normal and malignant
      hematopoiesis, but very few miRNAs have been shown to be consistently
      dysregulated in MDS. Even fewer candidate disease miRNAs have undergone
      functional validation, and the clinical relevance of these miRNAs remains to be
      determined. Despite the fact that MDS has been shown to be a disease initiated in
      hematopoietic stem cells (HSC), most existing studies examining miRNA expression
      in MDS have used unfractionated or only partially purified bone marrow (BM) cell
      populations, likely explaining in part the limited insight that provided by these
      studies. A more robust characterization of purified disease -initiating cell
      populations followed by rigorous functional validation using in vivo disease
      models will be vital to identifying dysregulated miRNAs of functional
      significance in MDS. Such studies promise to provide key insights into disease
      pathogenesis and potentially open new avenues towards the development of
      therapies targeting miRNAs themselves or the pathways that they regulate.

PMID- 25069442
TI  - Prevention of Lymphocyte Neurotoxic Effects by microRNA Delivery.
AB  - Aicardi Goutieres Syndrome (AGS) is characterized by mutations occurring in genes
      encoding RNAses. AGS mutations silence intracellular RNases resulting in an
      intracellular overload of short RNAs arresting the physiological production of
      microRNA required for brain development. MiR-219 is typically down-regulated in
      Aicardi Goutieres Syn-drome (AGS). The goal of this study is to investigate miR
      219 role in protecting astrocytes co-cultured with AGS-mutated lymphocytes. These
      lymphocytes display neurotoxic properties due to the presence of AGS-mutation and
      to their activa-tion by interpheron-alpha (IFN). Obtained results provide the
      evidence that astrocytes transfected with microRNA-219 are protected from the
      neurotoxic action of AGS lymphocytes activated by IFN-alpha. In particular, the
      miR-219 transfection increased astrocyte viability, growth, and differentiation
      while decreasing cell necrosis and apoptosis. Thus, microRNA-219 transfection is
      a valuable strategy in order to confer resistance to astrocytes towards
      lymphocyte-induced neurotoxici-ty especially in the presence of IFN-alpha, whose
      levels are typically increased in the cerebrospinal fluid of AGS patients.

PMID- 25069443
TI  - Tumor-Derived Exosomes Contain microRNAs with Immunological Function:
      Implications for a Novel Immunosuppression Mechanism.
AB  - Tumor-derived vesicles (TDV) have been recently implicated in immunosuppression
      by transporting specific proteins, including Fas ligand (FasL) and TRAIL, to
      immune cells. We hypothesized that TDVs carrying miRNAs with immunological
      function could interfere with the translational machinery of immune cells and
      lead to TDV-mediated immunosuppression in cancer. We show that TDVs from human
      tumor cells indeed contain multiple miRNA species with known roles in lymphocyte
      development and function: hsa-miR-146a, miR-29a, and miR-21. Quantification by RT
      PCR shows that the amount of miR-21 within TDVs isolated from the breast cancer
      cell line HCC1806 is at physiologically relevant levels. Additionally, we show
      that these miRNAs carried by TDVs copurify with argonaute proteins. This
      observation corroborates the idea that the machinery of microvesicle secretion
      and that of RNA interference are interconnected.

PMID- 25069444
TI  - MicroRNA Expression in Coronary Artery Disease.
AB  - The pathogenesis of atherosclerosis involves the interplay of inflammation,
      altered cellular activity, angiogenesis, and neointima formation. The main
      cellular participants in atherosclerosis include vascular endothelial cells,
      smooth muscle cells, and monocytes. The recent discovery of small, non-coding
      RNAs, microRNAs (miRNAs), and their influence on these processes has provided a
      greater molecular insight into atherosclerosis. This in turn has led to increase
      focus on the potential utility of miRNA subtypes as biomarkers for coronary
      artery disease. Furthermore miRNAs could potentially provide therapeutic targets
      for the treatment of atherosclerosis and its complications. In this review, we
      discuss the experimental and clinical evidence for the role of miRNAs in the
      pathogenesis of coronary artery disease, the limitations of the data and
      challenges facing the field.

PMID- 25069445
TI  - MicroRNAs and Major Blood-borne Infectious Viral Diseases.
AB  - The presence of microRNAs (miRNAs) and their ease of detection in body fluids
      including serum and whole blood have opened new avenues for developing novel non
      invasive methods for diagnostics and therapeutic applications for both infectious
      and noninfectious diseases. Blood-borne infectious viral diseases pose challenge
      to public health at large and, especially to health care workers, emergency
      responders and public safety personnel. Several studies have explored these newly
      identified miRNAs in blood borne infectious diseases for various purposes. This
      review highlights and focuses only on some of the available literature on the
      patient associated cellular miRNAs in blood-borne viral diseases and its
      occasional extrapolation to infected cell cultures as it relates to blood-borne
      hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus
      (HIV). Where appropriate, this review further points to the potential of miRNAs
      as non-invasive early disease detection biomarkers for these viral infections as
      well as possible prospects and challenges of miRNA-based therapies in treating
      these viral infections.

PMID- 25069446
TI  - Mutations in MicroRNA Genes and Their Binding Sites are Infrequently Associated
      with Human Colorectal Cancer in the Kashmiri Population.
AB  - MicroRNAs are small non-coding RNAs, 19-24 nucleotides in length that bind to the
      3'UTR of target mRNAs and thus regulate gene expression post transcriptionally.
      MiRNAs have been implicated in various biological and pathological processes. The
      binding of miRNAs to 3'UTR is crucial for regulating the mRNA level and hence
      protein expression. The complementarity between the miRNA and its target mRNA is
      critical for the outcome of the miRNA mediated translational regulation. Changes
      in the nucleotide sequence of either the miRNA or its target binding site can
      deregulate gene expression and hence lead to the development of various
      pathological conditions, including tumorigenesis. To determine whether sequence
      alterations in miRNA genes and their target sites in mRNAs are associated with
      the colorectal cancers, we screened two miRNA genes-Let-7c, mir-206 and selected
      miRNA binding regions on KRAS, TP53 and GJA1 3'UTR. This study was carried out on
      60 human colorectal cancer tissue samples. Our sequencing results did not reveal
      any mutation/single-nucleotide polymorphism in either the miRNAs or the miRNA
      binding sites in any of the tumor samples. This data suggests that mutations/SNPs
      targeting miRNA genes or their binding sites in 3'-untranslated regions are
      infrequent events in the development of colorectal cancer in Kashmiri population.

PMID- 25069447
TI  - Computational Identification of microRNA-like Elements in Leishmania major.
AB  - Leishmaniasis represents endemic infections that occur predominantly, in tropical
      and sub-tropical regions. The current situation for the chemotherapy of
      leishmaniasis is more promising than it has been for several decades with both
      new drugs and new formulations of old drugs either recently approved or in
      clinical trials. Investigations focused on parasite biology and identification of
      novel drug targets have become of great importance. The identification and
      characterization of microRNA (miRNAs) in the parasite and their possible
      biological action hopefully facilitate the discovery of potential antiparasitic
      drug targets against leishmaniasis. microRNA and other small RNA transcripts are
      derived from distinct loci in the genome and play critical roles in RNA-mediated
      gene silencing mechanisms in the organisms. miRNAs regulate mRNA stability
      through perfect and imperfect match to the targets. The biological activities of
      miRNAs have been related to many biological events, from resistant to microbe
      infections to cellular differentiation. miRNA like-elements have been identified
      in Leishmania major. Identification of miRNA-like elements in L. major provides a
      foundation for subsequent functional studies. Computational strategies provide an
      efficient manner to predict miRNA genes and their targets. Twenty-five potential
      miRNA-like elements in different chromosomes (chr.) like chr. 7(th), 8(th),
      17(th), 18(th), 21(st), 23(rd), 25(th), 26(th), 29(th), 31(st), 32(nd), 33(rd),
      34(th) and 35(th) of L. major have been identified. It is known from this study
      that the target genes of miRNA-like elements involve multidrug resistant protein
      such as ABC transporter, ribosomal protein, RNA binding proteins, hydrolase and
      exonuclease.

PMID- 25069448
TI  - Reinterventions in vascular and endovascular carotid surgery.
AB  - In recent years the number of carotid revascularization has increased steadily.
      This increased has inevitably resulted in an increase (relative) in
      complications, both after carotid endarterectomy (CEA) and carotid stenting
      (CAS), despite the technical evolutions of new available materials and the
      expertise of the operators. So, complications which may potentially require
      operative intervention, although not very frequent, are possible. However, after
      diagnosis, immediate management should be undertaken in order to avoid sequelae
      which are often irreversible and potentially fatal. To minimize this risk, it's
      important that these procedures are performed by skilled operators in high-volume
      Centers of activity. The aim of this review is to assess local complications
      which can lead to re-interventions after CEA and CAS. 

PMID- 25069449
TI  - Mesenteric ischemia after abdominal aortic aneurysm repair: a systemic review.
AB  - Mesenteric ischemia after abdominal aneurysm repair is a devastating complication
      with mortality rates up to 70%. Incidence however is relatively low. The aim of
      this review was to provide an overview on current insights, diagnostic modalities
      and on mesenteric ischemia after abdominal aortic aneurysm repair. 

PMID- 25069451
TI  - US doctors are judged more on bedside manner than effectiveness of care, survey
      finds.

PMID- 25069450
TI  - Bone modeling patterns and morphometric craniofacial variation in individuals
      from two prehistoric human populations from Argentina.
AB  - Native human populations from South America display high levels of craniofacial
      variation encompassing gracile and robust skulls. Nevertheless, the processes of
      bone modeling by which morphological variation among populations were attained,
      remain poorly understood. Here we analyze the relationship between patterns of
      bone formation and resorption and morphometric variation in the upper face of
      adults belonging to farmers and hunter-gatherers from northwestern and south
      Argentina. Our analyses reveal a common pattern of bone modeling of the malar
      bone characterized by the presence of formation areas. Thus, the larger size and
      greater development of malar bone exhibited by hunter-gatherers would be linked
      to a greater magnitude of bone formation activity. Conversely, the glabella and
      the superciliary arch presented both formation and resorption areas with a
      variable distribution among individuals. In the extreme corresponding to more
      robust morphologies, the great development of the glabella is related to the
      presence of large formation fields, both in the upper region and toward the
      frontonasal suture. The less robust morphologies show resorption fields at the
      upper margin of the glabella, which would contribute to the weaker development of
      this region. The superciliary arch showed a complex relationship between its
      morphometric and histological variation; the individuals located at both extremes
      of the shape space presented large resorption areas located on its upper margin.
      Overall, our results show the existence of intraspecific variation in the
      patterns of bone modeling in the human upper face.

PMID- 25069452
TI  - Importance of Arsenic and pesticides in epidemic chronic kidney disease in Sri
      Lanka.
AB  - In a recent study published by the National Project team on chronic kidney
      diseases of unknown origin in Sri Lanka, we believe there to be flaws in the
      design, analysis, and conclusions, which should be discussed further. The authors
      wanted to emphasis Cadmium as the major risk factor for chronic kidney disease of
      unknown etiology in Sri Lanka while undermining the importance of Arsenic and
      nephrotoxic pesticides. To arrive at predetermined conclusions the authors appear
      have changed and misinterpreted their own results. The enormous pressure applied
      by the agrochemical industry on this issue may be a factor. Herein, we discuss
      these issues in greater detail. 

PMID- 25069453
TI  - Biogenesis and multifaceted roles of outer membrane vesicles from Gram-negative
      bacteria.
AB  - Outer membrane vesicles (OMVs) released from Gram-negative bacteria consist of
      lipids, proteins, lipopolysaccharides and other molecules. OMVs are associated
      with several biological functions such as horizontal gene transfer, intracellular
      and intercellular communication, transfer of contents to host cells, and
      eliciting an immune response in host cells. Although hypotheses have been made
      concerning the mechanism of biogenesis of these vesicles, research on OMV
      formation is far from complete. The roles of outer membrane components, bacterial
      quorum sensing molecules and some specific proteins in OMV biogenesis have been
      studied. This review discusses the different models that have been proposed for
      OMV biogenesis, along with details of the biological functions of OMVs and the
      likely scope of future research. 

PMID- 25069454
TI  - Use of theoretical waste inventories in planning and monitoring of hazardous
      waste management systems.
AB  - Hazardous waste (HW) generation information is an absolute necessity for ensuring
      the proper planning, implementation, and monitoring of any waste management
      system. Unfortunately, environmental agencies in developing countries face
      difficulties in gathering data directly from the creators of such wastes. It is
      possible, however, to construct theoretical HW inventories using the waste
      generation factors (WGFs). The objective of this study was to develop a complete
      nationwide HW inventory of Turkey that relies on nation-specific WGFs to support
      management activities of the Turkish Ministry of Environment and Urbanization
      (MoEU). Inventory studies relied on WGFs from: (a) the literature and (b) field
      studies and analysis of waste declarations reflecting country-specific industrial
      practices. Moreover, new tools were introduced to the monitoring infrastructure
      of MoEU to obtain a comprehensive waste generation data set. Through field
      studies and a consideration of country specific conditions, it was possible to
      more thoroughly elucidate HW generation trends in Turkey, a method that was
      deemed superior to other alternatives. Declaration and literature based WGFs also
      proved most helpful in supplementing field observations that could not always be
      conducted. It was determined that these theoretical inventories could become
      valuable assets in supporting regulating agencies in developing countries for a
      more thorough implementation of HW management systems. 

PMID- 25069455
TI  - The depression in women in pregnancy and postpartum period: A follow-up study.
AB  - AIM: This was a follow-up study to determine postpartum depression (PPD) and its
      causes in a population previously evaluated in the first trimester of pregnancy.
      METHODS: The study sample consisted of pregnant women who were evaluated in the
      first trimester and 360 women who were re-evaluated in the postpartum period.
      Detailed sociodemographic data were obtained from the women, and depression was
      assessed with the Edinburgh Postpartum Depression scale (EPDS) and Structured
      Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders
      (DSM) Axis I Disorders (SCID-I). RESULTS: In this follow-up study, the prevalence
      of PPD was 35% (n = 126). A depressive disorder in the first trimester of
      pregnancy, previous mental disorder, somatic disorder, exposure to domestic
      violence during pregnancy, baby's staying in the incubator and not breastfeeding
      were predictors of PPD. Exposure to violence and a history of previous depression
      predicted depression both in pregnancy and in the postpartum period. CONCLUSION:
      Depression rates are high in Eastern Turkey. Exposure to violence during
      pregnancy and the existence of a previous mental disorder were risk factors for
      perinatal depression in this study. Performing screening tests can identify women
      at risk of pregnancy-related depression. Prevention programs should be
      established in areas where the prevalence of depression is high.

PMID- 25069456
TI  - 'Ego-dystonicity' in homosexuality: An Indian perspective.
AB  - BACKGROUND: Homosexual persons are targets of verbal and physical abuse,
      discrimination and face legal disadvantages in many countries, including India.
      These external factors could play a role in determining discomfort with their
      sexuality. AIMS: We ascertained the association between ego-dystonicity of sexual
      orientation and indices of perceived acceptance, stigma and awareness of possible
      normative lifestyles. METHODS: Fifty-one self-identified adult homosexual men
      were assessed using online questionnaires that covered information including
      their socio-demographic details; a Visual Analog Scale (VAS) that measured their
      degree of discomfort with their sexuality; Reactions to Homosexuality Scale,
      Perceived Acceptance Scale, Modified China Men Who Have Sex with Men (MSM) Stigma
      scale; and trait version of the Positive and Negative Affect Scale. The
      participants were also asked to provide a written narrative of their experiences
      which influenced their comfort with their sexuality. RESULTS: Discomfort with
      sexuality significantly correlated with education, acceptance by friends and
      family, legal disadvantages, awareness and accessibility to non-heteronormative
      lifestyles and support systems and trait affect. Only acceptance by friends and
      awareness showed significance on linear regression. Qualitative analyses revealed
      external attributions for discomfort. CONCLUSIONS: Modifying external factors,
      reducing legal restrictions and improving societal acceptance and support systems
      could reduce 'ego-dystonicity'. 'Ego-dystonicity' as a determinant for
      psychiatric classification and intervention needs to be reexamined.

PMID- 25069457
TI  - Antithyroid drugs and congenital heart defects: ventricular septal defect is part
      of the methimazole/carbimazole embryopathy.

PMID- 25069458
TI  - Androgen receptor expression in male breast cancer predicts inferior outcome and
      poor response to tamoxifen treatment.
AB  - OBJECTIVE: Androgen receptor (AR) plays an important role in male breast cancer
      (MBC). Additionally, endocrine therapy is the most important treatment in
      oestrogen receptor (ER)-positive advanced breast cancer. This study was aimed to
      investigate the role of AR in MBC treatment and prognosis and to analyse the
      relationship between AR and the effect of tamoxifen treatment in MBC patients.
      METHODS: AR protein levels and other tumour characteristics (e.g. expression of
      ER (ESR1), PR (PGR), AR, HER2 (ERBB2) and Ki-67 (MKI67)) in breast cancer tissue
      from 102 MBC patients were determined using immunohistochemical analysis.
      Additionally, the relationship between AR status and clinicopathological features
      was analysed using the chi(2)-test. Association with survival was initially
      analysed using the Kaplan-Meier method and the log-rank test, and Cox regression
      analysis was used to adjust for other prognostic indicators. RESULTS: High
      expression of AR was not correlated with T-stage, histological grade, HER2 status
      and the status of other sex hormone receptors, but was associated with lymph node
      metastases (P=0.032). AR-positive patients showed significantly shorter 5-year
      overall survival (OS) rates (P=0.045) and 5-year disease-free survival (DFS)
      rates (P=0.026) than AR-negative patients. By contrast, for patients who received
      tamoxifen therapy, AR-negative patients showed a higher clinical benefit rate
      than AR-positive patients (P=0.025). Additionally, the median TTP and OS were
      significantly different (P=0.02 for TTP; P=0.029 for OS). CONCLUSIONS: AR
      expression correlates strongly with both OS and DFS in patients with MBC. AR
      positive patients can predict a poorer clinical outcome than AR-negative patients
      after adjuvant tamoxifen therapy.

PMID- 25069459
TI  - Anticoagulant use for the prevention of stroke in patients with atrial
      fibrillation: findings from a multi-payer analysis.
AB  - BACKGROUND: Oral anticoagulation is recommended for stroke prevention in
      intermediate/high stroke risk atrial fibrillation (AF) patients. The objective of
      this study was to demonstrate the usefulness of analytic software tools for
      descriptive analyses of disease management in atrial AF; a secondary objective is
      to demonstrate patterns of potential anticoagulant undertreatment in AF. METHODS:
      Retrospective data analyses were performed using the Anticoagulant Quality
      Improvement Analyzer (AQuIA), a software tool designed to analyze health plan
      data. Two-year data from five databases were analyzed: IMS LifeLink (IMS),
      MarketScan Commercial (MarketScanCommercial), MarketScan Medicare Supplemental
      (MarketScanMedicare), ClinformaticsTM DataMart, a product of OptumInsight Life
      Sciences (Optum), and a Medicaid Database (Medicaid). Included patients were >=
      18 years old with a new or existing diagnosis of AF. The first observed AF
      diagnosis constituted the index date, with patient outcomes assessed over a one
      year period. Key study measures included stroke risk level, anticoagulant use,
      and frequency of International Normalized Ratio (INR) monitoring. RESULTS: High
      stroke risk (CHADS2 >= 2 points) was estimated in 54% (IMS), 22%
      (MarketScanCommercial), 64% (MarketscanMedicare), 42% (Optum) and 62% (Medicaid)
      of the total eligible population. Overall, 35%, 29%, 38%, 39% and 16% of all AF
      patients received an anticoagulant medication in IMS, MarketScanCommercial,
      MarketScanMedicare, Optum and Medicaid, respectively. Among patients at high risk
      for stroke, 19% to 51% received any anticoagulant. CONCLUSIONS: The AQuIA
      provided a consistent platform for analysis across multiple AF populations with
      varying baseline characteristics. Analyzer results show that many high-risk AF
      patients in selected commercial, Medicare-eligible, and Medicaid populations do
      not receive appropriate thromboprophylaxis, as recommended by treatment
      guidelines.

PMID- 25069461
TI  - Therapy: FGF1 restores blood glucose levels and insulin sensitivity in diabetic
      mice.

PMID- 25069462
TI  - Reproductive endocrinology: you are what your grandmother ate-inherited effects
      of in utero undernourishment.

PMID- 25069463
TI  - Diabetes: safety and efficacy of albiglutide-results from two trials.
AB  - Type 2 diabetes mellitus is associated with a poor quality of life and
      considerable health-care costs and can be difficult to control. The recent
      results from the HARMONY 3 and HARMONY 6 trials suggest that albiglutide is a
      safe and effective treatment option for patients with type 2 diabetes mellitus.

PMID- 25069467
TI  - Neuroendocrine cancer: CLARINET: new option for NETS.

PMID- 25069468
TI  - Diabetes: A role for CFTR in beta-cell function.

PMID- 25069464
TI  - Pax-8-PPAR-gamma fusion protein in thyroid carcinoma.
AB  - Thyroid carcinoma is the most common endocrine malignancy, and its incidence is
      continuing to increase. Most thyroid carcinomas contain one of several known
      driver mutations, such as the Val600Glu substitution in B-Raf, Ras mutations, RET
      gene fusions, or PAX8-PPARG gene fusions. The PAX8-PPARG gene fusion results in
      the production of a Pax-8-PPAR-gamma fusion protein (PPFP), which is found in
      approximately one-third of follicular thyroid carcinomas, as well as some
      follicular-variant papillary thyroid carcinomas. In vitro and in vivo evidence
      indicates that PPFP is an oncoprotein. Although specific mechanisms of action
      remain to be defined, PPFP is considered to act as a dominant-negative inhibitor
      of wild-type PPAR-gamma and/or as a unique transcriptional activator of subsets
      of PPAR-gamma-responsive and Pax-8-responsive genes. Detection of the fusion
      transcript in thyroid nodule biopsy specimens can aid clinical decision-making
      when cytological findings are indeterminate. The PPAR-gamma agonist pioglitazone
      is highly therapeutic in a transgenic mouse model of PPFP-positive thyroid
      carcinoma, suggesting that PPAR-gamma agonists might be beneficial in patients
      with PPFP-positive thyroid carcinomas. 

PMID- 25069471
TI  - Expression of BAG-1 is closely related to cell differentiation and TNM stage in
      esophageal cancer and its downregulation inhibits the proliferation and invasion
      of human esophageal carcinoma cells.
AB  - The aim of the present study was to explore the correlation of BAG-1 with
      clinical characteristics of esophageal cancer and its effects on the
      proliferation, invasion and apoptosis of the esophageal carcinoma cell line
      Eca109. Therefore, the expression of BAG-1 was assessed in esophageal carcinoma
      tumor tissues and adjacent normal esophageal tissues. The siRNA vector of BAG-1
      was constructed and transfected into the Eca109 cell line, and then fluorescence
      microscopy was used to evaluate the transfection efficiency. MTT and Transwell
      assays were used to study cell proliferation and invasive activity, and the
      apoptosis rate was assessed by flow cytometry. Western blotting was adopted to
      assess the silencing efficiency and expression of related gene bcl-2. The results
      revealed that BAG-1 expression was low in the adjacent normal esophageal tissues
      while expression was high in the esophageal carcinoma tissues. After Eca109 cells
      were transfected with BAG-1-siRNA, the proliferation and invasive capabilities of
      the cells were significantly decreased while the apoptosis rate was greatly
      enhanced (P<0.01). When the expression of BAG-1 in the Eca109 cells was
      downregulated, the expression of bcl-2 was significantly abated (P<0.05). In
      conclusion, BAG-1 is closely connected with the pathogenesis and development of
      esophageal carcinoma, which may act through affecting bcl-2. 

PMID- 25069472
TI  - Cavernous hemangioma of the third ventricle: a case report and review of the
      literature.
AB  - BACKGROUND: Although cavernous hemangiomas (CHs) can be found anywhere in the
      central nervous system, CHs of the third ventricle have been reported in only 29
      patients (including our case). In the current case report, we discuss the
      clinical characteristics and surgical outcome of CHs of the third ventricle. CASE
      PRESENTATION: A 64-year-old female was admitted to our emergency room with a
      sudden decreased level of consciousness. Brain imaging studies demonstrated a
      multi-lobulated hemorrhagic mass in the third ventricle. The lesion was removed
      via the transcallosal-interforniceal approach and pathologically diagnosed as CH.
      Postoperatively, the patient had a transient neurological deficit due to
      hypothalamic injury and recovered to the normal status at 2 months after the
      operation. In the review of 29 cases, the mean age of the patients was 40 years
      with a slight female preponderance (female/male, 17/12). The majority of the
      patients complained of a mass effect with signs of increased intracranial
      pressure; only one case was asymptomatic. Gross total resection was achieved in
      81% of the cases. Around 80% of the patients were asymptomatic or improved from
      the initial symptoms. Mortality rate was 6.9% and the most common complication
      was hydrocephalus. CONCLUSIONS: As demonstrated in the review of the previous
      reports, the outcome is favorable after surgical excision for CH of the third
      ventricle. Hence, surgical excision appears to be the treatment of choice for CH
      located in the third ventricle, which tends to grow rapidly resulting in a mass
      effect.

PMID- 25069473
TI  - Solid-state NMR and Raman spectroscopy to address the local structure of defects
      and the tricky issue of the Cu/Zn disorder in Cu-poor, Zn-rich CZTS materials.
AB  - The material Cu2ZnSn(S,Se)4 (CZTS) offers a promising indium-free alternative to
      Cu(In,Ga)Se2 for the absorber layer in thin-film solar cells. It is known that
      the highest solar energy conversion efficiencies are reached for Cu-poor, Zn-rich
      CZTS compositions and that too much disorder at the Cu and Zn sites can have a
      negative impact on the device performance. In this article, we investigate the
      structures of [VCu + ZnCu] A-type and [2ZnCu + ZnSn] B-type defect complexes and
      their impact on the long-range Cu/Zn disorder. To that end, we use (119)Sn,
      (65)Cu, and (67)Zn solid-state NMR and Raman spectroscopy to characterize
      powdered CZTS samples. For both A- and B-type substitutions, our NMR
      investigations demonstrate the clustering of the complexes. Moreover, we show
      that (A+B)-type compounds should be considered as A-type and B-type compounds,
      since no interaction seems to exist between [VCu + ZnCu] and [2ZnCu + ZnSn]
      defect complexes. In addition, it is worth noting that [2ZnCu + ZnSn] complexes
      have only a minor impact on the level of disorder at the Cu and Zn sites. In
      contrast, [VCu + ZnCu] complexes seem to restrain the random distribution of Cu
      at the Zn site and of Zn at the Cu site; i.e., the long-range Cu/Zn disorder.
      Raman characterization of the CZTS samples was also conducted. The Q = I287/I303
      and the newly introduced Q' = I338/(I366 + I374) ratios determined from Raman
      spectra collected at 785 nm turn out to be very sensitive to the level of Cu/Zn
      disorder. Moreover, they can be used to differentiate the nature of the
      substitution in slow-cooled materials. 

PMID- 25069474
TI  - Seeing the same GP each time can reduce emergency department attendance, review
      finds.

PMID- 25069475
TI  - Genes involved in pericyte-driven tumor maturation predict treatment benefit of
      first-line FOLFIRI plus bevacizumab in patients with metastatic colorectal
      cancer.
AB  - Pericytes are crucial for angiogenesis. The impact of pericyte function to
      bevacizumab efficacy in mCRC treatment has not been comprehensively examined.
      This retrospective study investigated germline polymorphisms in genes related to
      early pericyte maturation to predict bevacizumab efficacy in 424 patients of two
      clinical trials treated first line with FOLFIRI+bevacizumab. Eight single
      nucleotide polymorphisms (SNPs) were tested for potential biomarker value: RGS5
      (regulator of G-protein signaling 5; rs1056515, rs2661280), PDGFR-beta (platelet
      derived growth factor receptor-beta; rs2229562, rs2302273), CSPG4 (chondroitin
      sulfate proteoglycan NG2; rs8023621, rs1127648) and RALBP1 (RalA binding protein
      1; rs10989, rs329007). For progression-free survival (PFS), PDGFR-beta
      (rs2302273) was able to define significantly different patient cohorts in uni-
      and multivariate testing. RALPB1 (rs329007) showed predictive value for tumor
      response. The C allele in RGS5 (rs2661280) predicted longer overall survival and
      CSPG4 rs1127648 was associated with differences in PFS, but for both value was
      lost when multivariate analysis was applied. A comprehensive statistical analysis
      revealed that the biomarker value of the SNPs was dependent on primary tumor
      location. This is the first study to identify pericyte germline polymorphisms
      associated with clinical outcome in mCRC patients treated first line with
      FOLFIRI+bevacizumab. The differences seen with regard to primary tumor location
      may lead to further research to understand the clinical outcome differences seen
      in right- and left-sided colon cancer. 

PMID- 25069477
TI  - Purification and biochemical characterization of a fibrin(ogen)olytic
      metalloprotease from Macrovipera mauritanica snake venom which induces vascular
      permeability.
AB  - In the present study, a novel fibrin(ogen)olytic metalloprotease from Macrovipera
      mauritanica snake venom was purified and characterized in terms of enzyme
      kinetics and substrate specificity. The purified enzyme [termed snake venom
      metalloprotease-Macrovipera mauritanica (SVMP-MM)] was composed of a single
      polypeptide with an apparent molecular weight of 27 kDa, as shown by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminus of the enzyme
      was composed of NH(2)-QRFAPRYIEL-COOH, as determined by N-terminal sequencing.
      The Aalpha- and the Bbeta-chains of fibrinogen were completely cleaved by SVMP-MM
      within 20 and 480 min, respectively. However, the gamma-chain was much more
      resistant to digestion by the enzyme. The enzyme also exhibited proteolytic
      activity, cleaving the alpha-alpha polymer of cross-linked fibrin, but did not
      effectively digest the gamma-gamma polymer. To determine the kinetic parameters
      for SVMP-MM, a fluorescence-quenching peptide (termed o-aminobenzoic acid
      HTEKLVTS-2,4-dinitrophenyl-NH(2)) containing a K-L sequence for SVMP-MM cleavage
      was designed and synthesized. The optimal pH and temperature for the enzyme
      activity were found to be 5.5 and 37C, respectively, when the fluorogenic
      substrate was synthesized and used as a substrate. Among the various divalent
      cations tested, Ni(2+) and Cu(2+) showed strong inhibitory effects on enzyme
      activity, with an average of 69.6% inhibition. The enzyme activity was also
      inhibited by treatment with 1,10-phenanthroline, ethylenediaminetetraacetic acid
      and glycol-bis-(2-aminoethylether)-N,N,N',N'-tetra-acetic acid, but not with
      aprotinin, tosyl-lysine chloromethyl ketone and tosyl-phenylalanyl chloromethyl
      ketone, suggesting that SVMP-MM is a metalloprotease and not a serine protease.
      The enzymatic parameters, including the K(M), k(cat), and k(cat)/K(M) values were
      estimated to be 0.015 mM, 0.031 sec(-1), and 20.67 mM(-1)sec(-1), respectively.
      SVMP-MM induced vascular permeability by digesting type IV collagen. The results
      obtained in our study demonstrate that SVMP-MM is a fibrin(ogen)olytic P-I class
      metalloprotease, which can induce a hemorrhagic reaction in vivo.

PMID- 25069476
TI  - Clinical and pharmacogenomic implications of genetic variation in a Southern
      Ethiopian population.
AB  - Africa is home to genetically diverse human populations. We compared the genetic
      structure of the Wolaita ethnic population from Southern Ethiopia (WETH, n=120)
      with HapMap populations using genome-wide variants. We investigated allele
      frequencies of 443 clinically and pharmacogenomically relevant genetic variants
      in WETH compared with HapMap populations. We found that WETH were genetically
      most similar to the Kenya Maasai and least similar to the Japanese in HapMap.
      Variant alleles associated with increased risk of adverse reactions to drugs used
      for treating tuberculosis (rs1799929 and rs1495741 in NAT2), thromboembolism
      (rs7294, rs9923231 and rs9934438 in VKORC1), and HIV/AIDS and solid tumors
      (rs2242046 in SLC28A1) had significantly higher frequencies in WETH compared with
      African ancestry HapMap populations. Our results illustrate that clinically
      relevant pharmacogenomic loci display allele frequency differences among African
      populations. We conclude that drug dosage guidelines for important global health
      diseases should be validated in genetically diverse African populations. 

PMID- 25069478
TI  - miR-210 regulates esophageal cancer cell proliferation by inducing G2/M phase
      cell cycle arrest through targeting PLK1.
AB  - micro (mi)RNAs are short regulatory RNAs that negatively modulate protein
      expression at the post-transcriptional level, and are being considered as novel
      therapeutic targets for the treatment of cancer. In the present study, an
      elevated expression level of circulating miR-210 was observed in patients with
      esophageal squamous cell carcinoma (ESCC) for the first time, to the best of our
      knowledge, and the induction of miR-210 under hypoxic conditions in ESCC was
      confirmed. Cell counting kit-8 assay and bromodeoxyuridine incorporation assay
      indicated that miR-210 markedly inhibited the proliferation of ESCC cells. In
      addition, the effect of miR-210 on the cell cycle was examined. Transfection of
      miR-210 resulted in a significant increase in the proportion of cells in G2/M
      phase. Polo-like kinase 1 (PLK1) was investigated as a candidate target of miR
      210, which is a critical regulator of cell cycle transmission at multiple levels.
      It was demonstrated that miR-210 reduced the levels of PLK1 protein by binding
      the 3' untranslated region of its mRNA. The results of the present study
      demonstrated that miR-210 inhibited the proliferation of ESCC cells by inducing
      G2/M phase cell cycle arrest, and these effects of miR-210 were mediated by the
      targeting of PLK1.

PMID- 25069479
TI  - Fetal QRS extraction from abdominal recordings via model-based signal processing
      and intelligent signal merging.
AB  - Noninvasive fetal ECG (fECG) monitoring has potential applications in diagnosing
      congenital heart diseases in a timely manner and assisting clinicians to make
      more appropriate decisions during labor. However, despite advances in signal
      processing and machine learning techniques, the analysis of fECG signals has
      still remained in its preliminary stages. In this work, we describe an algorithm
      to automatically locate QRS complexes in noninvasive fECG signals obtained from a
      set of four electrodes placed on the mother's abdomen. The algorithm is based on
      an iterative decomposition of the maternal and fetal subspaces and filtering of
      the maternal ECG (mECG) components from the fECG recordings. Once the maternal
      components are removed, a novel merging technique is applied to merge the signals
      and detect the fetal QRS (fQRS) complexes. The algorithm was trained and tested
      on the fECG datasets provided by the PhysioNet/CinC challenge 2013. The final
      results indicate that the algorithm is able to detect fetal peaks for a variety
      of signals with different morphologies and strength levels encountered in
      clinical practice. 

PMID- 25069480
TI  - Study on the formation of liquid ordered phase in
      lysophospholipid/cholesterol/1,3-butanediol/ water and
      lysophospholipid/ceramide/1,3- butanediol/water systems.
AB  - Formation of a liquid ordered phase in lysophospholipid/cholesterol/1,3
      butanediol/water and lysophospholipid/ceramide/1,3-butanediol/water systems was
      investigated. Differential scanning calorimetry confirmed that a liquid ordered
      phase was formed in the lysophospholipid/cholesterol/1,3-butanediol/water system
      similar to that in phospholipid systems. The structure of liquid ordered phase
      was analyzed by using X-ray scattering measurements. It was revealed that the
      liquid ordered phase has a lamellar structure in which the hydrophobic chains are
      less ordered than in alpha-type crystals. On the other hand, in the
      lysophospholipid/ceramide/1,3-butanediol/water system, a liquid ordered phase was
      not formed. 

PMID- 25069481
TI  - Potential protective effects of Nigella sativa and Allium sativum against
      fructose-induced metabolic syndrome in rats.
AB  - Among famous medicinal plants with known antioxidant activity; black seed
      (Nigella sativa, NS) and garlic (Allium sativum) which have been used in
      traditional medicine. In recent years, rates of metabolic syndrome (MS) have been
      increasing globally. The present work was designed to study the potential
      protective effects of black seed and raw garlic homogenate against fructose
      induced MS in rats and to assess the benefits gained from their combination.
      Fifty male albino Wistar rats were divided into 5 groups. A control group was
      allowed to feed on normal chow and drink tap water. MS group was fed the same
      diet plus 10% fructose in drinking water. Treated groups received NS or garlic
      either alone or in combination as oral supplements along with high fructose diet
      for 8 weeks. Results revealed that body weight, liver weight, fasting blood
      glucose, serum triglycerides (TG), total cholesterol (TC) and low density
      lipoprotein cholesterol (LDL-C) levels were significantly increased while high
      density lipoprotein cholesterol (HDL-C) and the activities of Lactate
      dehydrogenase (LDH), glucose -6-phosphate dehydrogenase (G-6-PHD) and catalase in
      liver tissues were significantly decreased in MS group compared to the control
      group. Administration of NS or garlic either alone or in combination
      significantly ameliorated all the above-mentioned altered parameters. Treatment
      with both NS and garlic showed the utmost reduction in serum LDL-C and TG levels
      and could restore the activities of the studied enzymes in liver nearly to normal
      values. It was concluded that both NS and garlic were effective in attenuating
      multiple abnormalities of MS. Combination of these medicinal plants may have
      additional effectiveness in reducing serum TC, LDL-C and increasing HDL-C levels
      which could be a step in the prevention and management of MS.

PMID- 25069483
TI  - Virtual screening of gene expression regulatory sites in non-coding regions of
      the infectious salmon anemia virus.
AB  - BACKGROUND: Members of the Orthomyxoviridae family, which contains an important
      fish pathogen called the infectious salmon anemia virus (ISAV), have a genome
      consisting of eight segments of single-stranded RNA that encode different viral
      proteins. Each of these segments is flanked by non-coding regions (NCRs). In
      other Orthomyxoviruses, sequences have been shown within these NCRs that regulate
      gene expression and virulence; however, only the sequences of these regions are
      known in ISAV, and a biological role has not yet been attributed to these
      regions. This study aims to determine possible functions of the NCRs of ISAV.
      RESULTS: The results suggested an association between the molecular architecture
      of NCR regions and their role in the viral life cycle. The available NCR
      sequences from ISAV isolates were compiled, alignments were performed to obtain a
      consensus sequence, and conserved regions were identified in this consensus
      sequence. To determine the molecular structure adopted by these NCRs, various
      bioinformatics tools, including RNAfold, RNAstructure, Sfold, and Mfold, were
      used. This hypothetical structure, together with a comparison with influenza,
      yielded reliable secondary structure models that lead to the identification of
      conserved nucleotide positions on an intergenus level. These models determined
      which nucleotide positions are involved in the recognition of the vRNA/cRNA by
      RNA-dependent RNA polymerase (RdRp) or mRNA by the ribosome. CONCLUSIONS: The
      information obtained in this work allowed the proposal of previously unknown
      sites that are involved in the regulation of different stages of the viral cycle,
      leading to the identification of new viral targets that may assist future
      antiviral strategies.

PMID- 25069484
TI  - The role of immune and metabolic biomarkers for improved management of sepsis
      patients.
AB  - Sepsis, the body's overwhelming response to systemic infections, is responsible
      for significant morbidity, mortality, and financial burden. Pathogens and their
      antigens stimulate pro- and anti-inflammatory mediators and immune markers which
      characterize the host defense and orchestrate leukocyte recruitment to the acute
      site of infection. Different immune and metabolic biomarkers have been studied in
      relation to sepsis for their diagnostic and/or prognostic aid. Recent studies
      have provided abundant evidence that specific immune and metabolic biomarkers
      improve a physician's ability to guide early sepsis recognition, severity
      assessment and therapeutic decisions in individual patients. This may allow for a
      transition from bundled sepsis care (protocols combining several medical
      practices) to more individualized management. First, lactate has now been widely
      used for risk stratification and guidance of fluid resuscitation. Second,
      procalcitonin correlates with risks of bacterial infections and helps guide
      therapeutic decisions about initiation and withdrawal of anti-microbial therapy.
      Third, prognostic markers such as pro-adrenomedullin improve early mortality
      prediction and thereby site-of-care decisions in respiratory infections. For
      these markers interventional trials have documented their value when integrated
      in clinical protocols. 

PMID- 25069482
TI  - Functional connectivity in autosomal dominant and late-onset Alzheimer disease.
AB  - IMPORTANCE: Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic
      mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD),
      which has a more polygenetic risk profile. OBJECTIVE: To assess the similarities
      and differences in functional connectivity changes owing to ADAD and LOAD.
      DESIGN, SETTING, AND PARTICIPANTS: We analyzed functional connectivity in
      multiple brain resting state networks (RSNs) in a cross-sectional cohort of
      participants with ADAD (n = 79) and LOAD (n = 444), using resting-state
      functional connectivity magnetic resonance imaging at multiple international
      academic sites. MAIN OUTCOMES AND MEASURES: For both types of AD, we quantified
      and compared functional connectivity changes in RSNs as a function of dementia
      severity measured by the Clinical Dementia Rating Scale. In ADAD, we
      qualitatively investigated functional connectivity changes with respect to
      estimated years from onset of symptoms within 5 RSNs. RESULTS: A decrease in
      functional connectivity with increasing Clinical Dementia Rating scores were
      similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression
      models constructed in one type of Alzheimer disease accurately predicted clinical
      dementia rating scores in the other, further demonstrating the similarity of
      functional connectivity loss in each disease type. Among participants with ADAD,
      functional connectivity in multiple RSNs appeared qualitatively lower in
      asymptomatic mutation carriers near their anticipated age of symptom onset
      compared with asymptomatic mutation noncarriers. CONCLUSIONS AND RELEVANCE:
      Resting-state functional connectivity magnetic resonance imaging changes with
      progressing AD severity are similar between ADAD and LOAD. Resting-state
      functional connectivity magnetic resonance imaging may be a useful end point for
      LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an
      effective model for the LOAD disease process.

PMID- 25069485
TI  - Additional perspectives on chronic kidney disease of unknown aetiology (CKDu) in
      Sri Lanka--lessons learned from the WHO CKDu population prevalence study.
AB  - The recent emergence of an apparently new form of chronic kidney disease of
      unknown aetiology (CKDu) has become a serious public health crisis in Sri Lanka.
      CKDu is slowly progressive, irreversible, and asymptomatic until late stages, and
      is not attributable to hypertension, diabetes, or other known aetiologies. In
      response to the scope and severity of the emerging CKDu health crisis, the Sri
      Lanka Ministry of Health and the World Health Organization initiated a
      collaborative research project from 2009 through 2012 to investigate CKDu
      prevalence and aetiology. The objective of this paper is to discuss the recently
      published findings of this investigation and present additional considerations
      and recommendations that may enhance subsequent investigations designed to
      identify and understand CKDu risk factors in Sri Lanka or other countries. 

PMID- 25069486
TI  - Knockdown of galectin-1 suppresses the growth and invasion of osteosarcoma cells
      through inhibition of the MAPK/ERK pathway.
AB  - Galectin-1 (GAL1), a widely expressed beta-galacto-side-binding protein, exerts
      pleiotropic biological functions. GAL1 has been found to be upregulated in many
      malignancies; yet the role of GAL1 in the pathophysiology of human osteosarcoma
      (OS) remains uncertain. The present study was carried out to investigate the
      expression of GAL1 in human OS tissues and to explore its effects on the growth
      and invasion of OS cells. OS and corresponding adjacent non-cancerous tissues
      (ANCT) were collected from 30 consecutive cases. The expression of GAL1 was
      detected by immunohistochemical assay through tissue microarray procedure. Using
      small hairpin RNA (shRNA)-mediated GAL1 knockdown (Lv-shGAL1) in OS (MG-63 and U
      2 OS) cells, we observed the changes in the malignant phenotype in OS cells in
      vitro and in vivo. As a consequence, the positive expression of GAL1 was
      significantly higher in OS tissues than that in the ANCT (63.3 vs. 36.7%,
      P=0.029), and was positively correlated with distant metastasis in the OS
      patients (P=0.022). Knockdown of GAL1 suppressed cell proliferative activities
      and invasive potential and induced apoptosis in OS cells with decreased
      expression of p38MAPK, p-ERK, Ki-67 and matrix metallopeptidase-9 (MMP-9) and
      increased expression of caspase-3. In addition, the tumor volume in the MG-63
      subcutaneous tumor models treated with Lv-shGAL1 was significantly smaller than
      that in the negative control (NC) group (P<0.01). Altogether, our findings
      indicate that high expression of GAL1 is associated with distant metastasis of OS
      patients, and knockdown of GAL1 inhibits growth and invasion of OS cells possibly
      through inhibition of the MAPK/ERK pathway, suggesting that GAL1 may represent a
      potential target for the treatment of cancer. 

PMID- 25069487
TI  - Matrix metalloproteinases and peripheral arterial disease.
AB  - It has been postulated that atherosclerosis should be considered as a chronic
      inflammatory process and peripheral arterial disease (PAD) is a manifestation of
      such an atherosclerotic vascular disease. Matrix metalloproteinases (MMPs) are
      significant circulating biomarkers which play a pivotal role in the initiation,
      progression and clinical manifestations of PAD. This review summarizes the
      current body of evidence with regard to the association between MMPs and PAD. 

PMID- 25069488
TI  - Differences in arterial stiffness and target organ damage between native Greek
      patients and immigrants from Eastern European countries with essential
      hypertension.
AB  - AIM: The variance in hypertension-related sequelae between different ethnic
      groups is highly related to differences in socioeconomic conditions and lifestyle
      habits, but also to disparities in the awareness and treatment of the disease. In
      the present study, we sought to evaluate the target organ damage in a vulnerable
      hypertensive population, such as the Eastern European immigrants. METHODS: The
      study population consisted of 128 hypertensive patients: 67 immigrants from
      Eastern Europe and 61 native inhabitants. Anthropometric, biochemical and
      echocardiographic data were derived from both groups. Both groups underwent
      fundoscopic examination and pulse wave velocity (PWV) measurements for assessment
      of arterial stiffness. RESULTS: Although immigrants had lower body mass index
      compared to native inhabitants (P<0.001), they had significantly increased
      arterial stiffness (P=0.003). In multivariate analysis, higher carotid-femoral
      PWV was significantly associated with immigration status [beta (SE)=0.935(0.443),
      P=0.041], after adjustment for smoking status. Moreover, immigrants had increased
      left atrial volume index (LAVI) (P<0.001), left ventricular mass index (P<0.001)
      and higher rates of left ventricular diastolic dysfunction (p=0.047). In
      multivariate analysis, LAVI was significantly associated with immigration status
      (beta (SE)=5.17(1.93), P=0.01) after adjustment for serum glucose levels and age.
      Finally, immigrants had significantly higher levels of sodium urinary excretion
      (p=0.007) and lower glomerular filtration rate (P<0.001). CONCLUSION: Our
      findings suggest that hypertensive immigrants exhibit an aggravated arterial
      stiffness profile and increased risk of target organ damage. These findings could
      be attributed to differences in socioeconomic conditions and dietary habits.

PMID- 25069489
TI  - DNA methylation: Switching phenotypes with epialleles.

PMID- 25069492
TI  - Metabolic bone diseases: an overview.

PMID- 25069490
TI  - Investigating human disease using stem cell models.
AB  - Tractable and accurate disease models are essential for understanding disease
      pathogenesis and for developing new therapeutics. As stem cells are capable of
      self-renewal and differentiation, they are ideally suited both for generating
      these models and for obtaining the large quantities of cells required for drug
      development and transplantation therapies. Although proof of principle for the
      use of adult stem cells and embryonic stem cells in disease modelling has been
      established, induced pluripotent stem cells (iPSCs) have demonstrated the
      greatest utility for modelling human diseases. Furthermore, combining gene
      editing with iPSCs enables the generation of models of genetically complex
      disorders. 

PMID- 25069491
TI  - Are serum-free and xeno-free culture conditions ideal for large scale clinical
      grade expansion of Wharton's jelly derived mesenchymal stem cells? A comparative
      study.
AB  - INTRODUCTION: Mesenchymal stromal/stem cells (MSCs) for clinical use have largely
      been isolated from the bone marrow, although isolation of these cells from many
      different adult and fetal tissues has been reported as well. One such source of
      MSCs is the Whartons Jelly (WJ) of the umbilical cord, as it provides an
      inexhaustible source of stem cells for potential therapeutic use. Isolation of
      MSCs from the umbilical cord also presents little, if any, ethical concerns, and
      the process of obtaining the cord tissue is relatively simple with appropriate
      consent from the donor. However, a great majority of studies rely on the use of
      bovine serum containing medium for isolation and expansion of these cells, and
      porcine derived trypsin for dissociating the cells during passages, which may
      pose potential risks for using these cells in clinical applications. It is
      therefore of high priority to develop a robust production process by optimizing
      culture variables to efficiently and consistently generate MSCs that retain
      desired regenerative and differentiation properties while minimizing risk of
      disease transmission. METHODS: We have established a complete xeno-free, serum
      free culture condition for isolation, expansion and characterization of WJ-MSCs,
      to eliminate the use of animal components right from initiation of explant
      culture to clinical scale expansion and cryopreservation. Growth kinetics, in
      vitro differentiation capacities, immunosuppressive potential and
      immunophenotypic characterization of the cells expanded in serum-free media have
      been compared against those cultured under standard fetal bovine serum (FBS)
      containing medium. We have also compared the colony-forming frequency and genomic
      stability of the large scale expanded cells. Secretome analysis was performed to
      compare the angiogenic cytokines and functional angiogenic potency was proved by
      Matrigel assays. RESULTS: Results presented in this report identify one such
      serum-free, xeno-free medium for WJ expansion. Cells cultured in serum-free, xeno
      free medium exhibit superior growth kinetics and functional angiogenesis,
      alongside other MSC characteristics. CONCLUSIONS: We report here that WJ-MSCs
      cultured and expanded in Mesencult XF, SF Medium retain all necessary
      characteristics attributed to MSC for potential therapeutic use.

PMID- 25069493
TI  - Emerging therapies for osteoporosis.
AB  - Currently available drugs for the treatment of osteoporosis can still be improved
      in terms of pharmacokinetics, pharmacodynamics and management. New approaches for
      the development of innovative drugs are possible thanks to our increasing
      understanding of the bone tissue biology and the cellular and molecular processes
      that regulate it. One of the new anti-bone resorption agents, odanacatib, a
      selective cathepsin-K inhibitor, is in late phase III clinical research. Among
      new bone anabolic drugs, those that have an action on the Wnt signaling pathway
      appear to be particularly promising. The development of new compounds for the
      treatment of osteoporosis represents an excellent example of translational
      medicine efforts aimed to extend the range of treatment options for osteoporosis,
      a very common disease with a high social and economic impact, particularly when
      causing fractures. 

PMID- 25069494
TI  - Osteoporosis and rheumatic diseases.
AB  - Numerous rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic
      arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus
      erythematosus, systemic sclerosis, dermatomyositis/polymyositis and vasculitis
      are characterized by osteoporosis and fragility fractures. Inflammatory
      cytokines, glucocorticoid treatment, immobilization and reduced physical activity
      due to painful joints and muscle weakness are considered the main risk factors
      that cause low body mass density values in these diseases. Emerging evidence
      highlights the role of inflammatory cytokines, such as tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1, IL-6, IL-7 and IL-17, in the regulation of the
      bone homeostasis. In fact, chronic inflammation is often characterized by an
      imbalance between bone formation and bone resorption with a net prevalence of
      osteoclastogenesis, which is an important determinant of bone loss in rheumatic
      diseases. 

PMID- 25069495
TI  - Male osteoporosis.
AB  - As a result of population ageing worldwide, osteoporotic fractures are becoming a
      serious problem in the western world. Osteoporotic fractures are associated with
      a significant burden in terms of morbidity, mortality, and economic costs.
      Although less frequent than in women, male osteoporosis is also a relatively
      common problem. Since bone loss and fragility fractures in men have been
      recognized as a serious medical condition, over the last two decades several
      studies have investigated a number of aspects related to the pathogenesis,
      diagnosis and assessment, prevention and treatment of male osteoporosis. A better
      understanding of factors underlying increased bone fragility in men has led to
      the definition of appropriate screening and diagnostic strategies, and the
      development of treatments that have shown to improve bone mineral density and, in
      some cases, reduce fracture risk in men as well as in women. This review will
      summarize recent findings on male osteoporosis with a particular focus on risk
      factors and causes of bone loss, and available therapeutic options. 

PMID- 25069496
TI  - Glucocorticoid-induced osteoporosis: 2013 update.
AB  - Glucocorticoids are the most common cause of secondary osteoporosis leading to
      the so-called glucocorticoid-induced osteoporosis (GIO). A treatment with 10 mg/d
      of prednisone or equivalent for more than 3 months leads to a 7-fold increase in
      hip fractures and a 17-fold increase in vertebral fractures. The difference
      between bone quantity and quality in GIO makes bone mineral density measurements
      inadequate to detect patients at risk of fracture. The adverse effects of
      glucocorticoids on the skeleton derive from a direct impact on bone cells with a
      severe impairment of mechanical competence. Crucial to prevention of GIO is early
      timing of intervention. The World Health Organization has adopted a fracture
      prevention algorithm (FRAX) intended to estimate fracture risk in GIO. The
      American College of Rhematology modified its prevention and treatment guidelines
      taking into account the individual risk of fracture calculated in GIO on the
      basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of
      the International Osteoporosis Foundation (IOF) and the European Calcified Tissue
      Society (ECTS) published a framework for the development of national guidelines
      for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO;
      teriparatide counteracts several fundamental pathophysiologic aspects of GIO;
      denosumab is useful in patients with renal failure and in potentially pregnant
      young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in
      primary involutional osteoporosis.

PMID- 25069497
TI  - Vitamin D and rheumatic diseases.
AB  - Vitamin D has some well-known effects on calcium, phosphate and bone metabolism,
      but it has recently shown to have many other effects, which may potentially be
      relevant to patients with extra-skeletal rheumatic diseases. Such effects may be
      justified by: 1) the presence of the vitamin D receptors also on extra-osseous
      cells, such as cartilage cells, sinoviocytes, muscle cells; 2) the proven role of
      vitamin D in the control of the transcription of genes involved in rheumatic
      diseases; 3) the evidence that vitamin D has multiple endocrine effects not only
      on calcium homeostasis; 4) the activation of vitamin D not only in the kidneys,
      but also in monocyte-macrophage and lymphocytic cell lines and in some epithelial
      cells with additional intracrine and paracrine effects. Vitamin D deficiency has
      been reported in numerous metabolic, degenerative, inflammatory and autoimmune
      rheumatic diseases. In some cases this association was also related to the risk
      of developing a rheumatic disease or the degree of disease activity. However
      there is no conclusive evidence of the efficacy of a preventive or therapeutic
      strategy based on vitamin D supplementation in extra-skeletal rheumatic diseases.
      This review aims to provide an overview of the latest evidence concerning the
      relationship between vitamin D and the most relevant rheumatic diseases. 

PMID- 25069498
TI  - Paget's disease.
AB  - Paget's disease of bone is the most common metabolic bone disease after
      osteoporosis and affects 2-4% of adults over 55 years of age. Its etiology is
      only partly understood and includes both genetic and environmental factors. The
      disease may be asymptomatic and can be uncovered incidentally on x-ray or in
      biochemical tests performed for another condition. It can also manifest itself
      with bone pain, deformity, fracture or other complications. Paget's disease is
      diagnosed by x-rays and in general has very typical radiological features, but
      occasionally the clinical picture may be unusual and a differential diagnosis of
      sclerotic or lytic metastases needs to be considered. Plasma total alkaline
      phosphatase activity is the most clinically useful indicator of disease activity.
      It is elevated in most untreated patients, but may be within the normal range in
      patients with monostotic or limited disease. Bisphosphonate therapy is indicated
      for patients with symptoms and should also be considered in patients with disease
      sites that suggest a risk of complications, such as long bones, vertebrae or base
      of the skull. Orthopedic surgery in Paget's disease patients includes almost
      exclusively the correction of fractures and arthroplasty. 

PMID- 25069499
TI  - A clinical overview of bone marrow edema.
AB  - Bone marrow edema (BME) is a descriptive term which identifies a specific
      magnetic resonance imaging (MRI) pattern that can be observed in a number of
      clinical entities, which are often characterized by pain as their main symptom,
      but show significant differences in terms of histopathological findings, causal
      mechanisms and prognosis. Bone marrow lesions in the subchondral bone of subjects
      with knee osteoarthritis (OA) seem to be associated with pain and progression of
      cartilage damage over time. Some histopathological studies of advanced OA have
      shown a prevalent fibrosis and bone marrow necrosis. BME of the subchondral bone
      in rheumatoid arthritis is associated with an infiltrate of inflammatory cells
      and osteoclasts and has a predictive value of further development of erosions. In
      spondyloarthritis, BME of the sacroiliac joints identifies an active sacroiliitis
      and is associated with histological inflammation and radiographic progression,
      whereas the relationship between BME lesions of the spine and syndesmophyte
      development is still controversial. BME syndromes (BMES), such as transient
      osteoporosis of the hip, regional migratory osteoporosis, and transient post
      traumatic BMES, are characterized by a BME pattern on MRI and a self-limiting
      course. The potential evolution of BMES toward osteonecrosis is still
      controversial. 

PMID- 25069500
TI  - Referral for fertility preservation counselling in female cancer patients.
AB  - STUDY QUESTION: What changes can be detected in fertility preservation (FP)
      counselling (FPC) over time and what are the determinants associated with the
      referral of newly diagnosed female cancer patients, aged 0-39 years, to a
      specialist in reproductive medicine for FPC? SUMMARY ANSWER: Although the
      absolute number of patients receiving FPC increased over time, only 9.8% of all
      potential patients (aged 0-39 years) were referred in 2011 and referral
      disparities were found with respect to patients' age, cancer diagnosis and
      healthcare provider-related factors. WHAT IS KNOWN ALREADY: Referral rates for
      FPC prior to the start of gonadotoxic cancer treatment are low. Determinants
      associated with low referral and referral disparities have been identified in
      previous studies, although there are only scarce data on referral practices and
      determinants for FPC referral in settings with reimbursement of FP(C). STUDY
      DESIGN, SIZE, DURATION: We conducted a retrospective observational and
      questionnaire study in a Dutch university hospital. Data on all female cancer
      patients counselled for FP in this centre (2001-2013), as well as all newly
      diagnosed female cancer patients aged 0-39 years in the region (2009-2011) were
      collected. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were retrieved from
      medical records (FPC patients), cancer incidences reported by the Dutch Cancer
      Registry (to calculate referral percentages) and referring professionals (to
      identify reasons for the current referral behaviour). MAIN RESULTS AND THE ROLE
      OF CHANCE: In 2011, a total of 9.8% of the patients were referred for FPC.
      Patients aged 20-29 years or diagnosed with breast cancer or lymphoma were
      referred more frequently compared with patients under the age of 20 years or
      patients diagnosed with other malignancies. The absolute numbers of patients
      receiving FPC increased over time. Healthcare provider-related determinants for
      low referral were not starting a discussion about fertility-related issues, not
      knowing where to refer a patient for FPC and not collaborating with patients'
      associations. LIMITATIONS, REASONS FOR CAUTION: Actual referral rates may
      slightly differ from our estimation as there may have been patients who did not
      wish to receive FPC. Sporadically, patients might have been directly referred to
      other regions or may have received ovarian transposition without FPC. By
      excluding skin cancer patients, we will have underestimated the group of women
      who are eligible for FPC as this group also includes melanoma patients who might
      have received gonadotoxic therapy. WIDER IMPLICATIONS OF THE FINDINGS: The low
      referral rates and referral disparities reported in the current study indicate
      that there are opportunities to improve referral practices. Future research
      should focus on the implementation and evaluation of interventions to improve
      referral practices, such as information materials for patients at oncology
      departments, discussion prompts or methods to increase the awareness of
      physicians and patients of FP techniques and guidelines. STUDY FUNDING/COMPETING
      INTERESTS: This work was supported by the Radboud university medical center and
      the Radboud Institute for Health Sciences. The authors have declared no conflicts
      of interest with respect to this work. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 25069501
TI  - The role of the cervix in fertility: is it time for a reappraisal?
AB  - Knowledge regarding the role of the cervix in fertility has expanded considerably
      over the past 20 years and in this article, we propose that it is now time for
      its function to be reappraised. First, we review the anatomy of the cervix and
      the vaginal ecosystem that it inhabits. Then, we examine the physiology and the
      role of the cervical mucus. The ongoing mystery of the exact mechanism of the
      sperm-cervical mucus interaction is reviewed and the key players that may unlock
      this mystery in the future are discussed. The soluble and cellular biomarkers of
      the lower female genital tract which are slowly being defined by contemporary
      research are reviewed. Attempts to standardize these markers, in this milieu, are
      hindered by the changes that may be attributed to endogenous or exogenous factors
      such as: age, hormonal changes during the menstrual cycle, ectropion, infection,
      smoking and exposure to semen during sexual intercourse. We review what is known
      about the immunology of the cervix. With the widespread use of large loop
      excision of the transformation zone (LLETZ) for treatment of cervical
      intraepithelial neoplasia, the anatomy of the cervix is changing for many women.
      While LLETZ surgery has had very positive effects in the fight against cervical
      cancer, we debate the impact it could have on a woman's fertility. 

PMID- 25069503
TI  - Birthweight distribution in ART singletons resulting from embryo culture in two
      different culture media compared with the national population.
AB  - STUDY QUESTION: Is there a difference in birthweight distribution in ART
      singletons born after IVF culture in two different culture media? SUMMARY ANSWER:
      There is no effect of culture media on both crude and adjusted birthweight
      distributions in ART singletons from nulliparous mothers. WHAT IS KNOWN ALREADY:
      Studies on human ART singletons have reported a difference in birthweight in
      singletons following IVF culture in different culture media. However, other
      studies comparing different culture media have not shown any significant
      differences in birthweight. STUDY DESIGN, SIZE, DURATION: This study was a
      retrospective comparison of birthweights in IVF/ICSI singletons conceived after
      fresh embryo transfer following embryo culture in Cook or Medicult medium and in
      a national cohort of naturally conceived singletons in nulliparous women. The
      study compares four independent groups consisting of singletons in nulliparous
      women from Cook-d2: 2-day culture in Cook medium at Rigshospitalet (n = 974),
      Medicult-d2: 2-day culture in Medicult EmbryoAssist medium at Rigshospitalet (n =
      147), Medicult-d3: 3-day culture in Medicult EmbryoAssist medium with and without
      added GM-CSF (n = 204), and DK: pregnancies from the Danish birth registry (n =
      106842). PARTICIPANTS/MATERIALS, SETTING, METHODS: The study compares the
      birthweights of singletons from nulliparous women in the four independent groups
      mentioned above; Cook-d2: Medicult-d2: Medicult-d3: and DK. In addition,
      distributions of large and small for gestational age infants were compared
      between the groups and a multiple linear regression analysis was used to
      determine which factors determined birthweight. MAIN RESULTS AND THE ROLE OF
      CHANCE: We found no significant difference in the crude birthweight distributions
      between singletons born after culture in Cook-d2 or Medicult-groups. Singleton
      girls from the Cook-d2 group weighed 3302 +/- 28 g, versus 3252 +/- 76 in the
      Medicult-d2 group (difference 50 g; P = 0.547). Singleton boys from the Cook-d2
      group weighed 3430 +/- 27 g, versus 3354 +/- 56 in the Medicult-d2 group
      (difference 76 g; P = 0.279). In the background population, mean birthweights for
      singleton girls and boys were 3383 +/- 2.4 g and 3494 +/- 2.5 g, respectively.
      The mean birthweights of girls, 3315 +/- 61 g, and boys, 3383 +/- 64 g, in the
      Medicult-d3 group were not significantly different from that in the Medicult-d2
      group. When pooling data from all culture media groups, we found the same
      slightly lower mean birthweight in IVF/ICSI singletons when compared with the
      national birth cohort as has been previously reported (Cook-d2 + Medicult-d2 + d3
      versus birth cohort; girls: P < 0.001, boys: P < 0.001). We also pooled data on
      boys and girls and calculated the mean birthweight for the Cook-d2, Medicult-d2
      and Medicult-d3 groups and found no significant differences. LIMITATIONS, REASONS
      FOR CAUTION: The retrospective design and the inherent risk of confounding
      factors is a limitation. Selection bias cannot be excluded as the embryos
      cultured in Cook-d2 and Medicult-d2 were from single centre studies while data in
      Medicult-D3 group were derived from a multicentre study. WIDER IMPLICATIONS OF
      THE FINDINGS: This large cohort of singletons born after IVF/ICSI shows no
      difference in crude mean birthweight after culture in two different culture
      media, indicating that if such a difference exists, this must be specific for
      certain culture media. As expected we found a slightly lower mean birthweight in
      ART compared with naturally conceived singletons. This suggests that parental
      characteristics or IVF technique related factors other than type of culture
      medium may influence the birthweight in ART singletons. STUDY FUNDING/COMPETING
      INTERESTS: No external funding was used for this study. No conflicts of interest
      are declared.

PMID- 25069502
TI  - Human sperm sex chromosome disomy and sperm DNA damage assessed by the neutral
      comet assay.
AB  - STUDY QUESTION: Is there an association between human sperm sex chromosome disomy
      and sperm DNA damage? SUMMARY ANSWER: An increase in human sperm XY disomy was
      associated with higher comet extent; however, there was no other consistent
      association of sex chromosome disomies with DNA damage. WHAT IS KNOWN ALREADY:
      There is limited published research on the association between sex chromosome
      disomy and sperm DNA damage and the findings are not consistent across studies.
      STUDY DESIGN, SIZE, AND DURATION: We conducted a cross-sectional study of 190 men
      (25% ever smoker, 75% never smoker) from subfertile couples presenting at the
      Massachusetts General Hospital Fertility Clinic from January 2000 to May 2003.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Multiprobe fluorescence in situ
      hybridization for chromosomes X, Y and 18 was used to determine XX, YY, XY and
      total sex chromosome disomy in sperm nuclei using an automated scoring method.
      The neutral comet assay was used to measure sperm DNA damage, as reflected by
      comet extent, percentage DNA in the comet tail, and tail distributed moment.
      Univariate and multiple linear regression models were constructed with sex
      chromosome disomy (separate models for each of the four disomic conditions) as
      the independent variable, and DNA damage parameters (separate models for each
      measure of DNA damage) as the dependent variable. MAIN RESULTS AND THE ROLE OF
      CHANCE: Men with current or past smoking history had significantly greater comet
      extent (um: regression coefficients with 95% CI) [XX18: 15.17 (1.98, 28.36);
      YY18: 14.68 (1.50, 27.86); XY18: 15.41 (2.37, 28.45); Total Sex Chromosome
      Disomy: 15.23 (2.09, 28.38)], and tail distributed moment [XX18: 3.01 (0.30,
      5.72); YY18: 2.95 (0.24, 5.67); XY18: 3.04 (0.36, 5.72); Total Sex Chromosome
      Disomy: 3.10 (0.31, 5.71)] than men who had never smoked. In regression models
      adjusted for age and smoking, there was a positive association between XY disomy
      and comet extent. For an increase in XY disomy from 0.56 to 1.47% (representing
      the 25th to 75th percentile), there was a mean increase of 5.08 um in comet
      extent. No other statistically significant findings were observed. LIMITATIONS,
      REASONS FOR CAUTION: A potential limitation of this study is that it is cross
      sectional. Cross-sectional analyses by nature do not lend themselves to inference
      about directionality for any observed associations; therefore we cannot determine
      which variable is the cause and which one is the effect. A small sample size may
      be a further limitation. Comparison of these findings to other studies is limited
      due to methodological differences. WIDER IMPLICATIONS OF THE FINDINGS: Although
      consistent associations across sex chromosome disomies or DNA damage measures
      were not observed, this study highlights the need to explore etiologies of sperm
      DNA damage and sex chromosome disomy to better understand the potential
      mechanistic overlaps between the two. STUDY FUNDING/COMPETING INTERESTS: This
      work was supported by NIOSH Grant T42 OH008416, and NIH/NIEHS Grants ES 009718,
      ES 000002, and R01 ES017457. During the study M.E.M. was affiliated with the
      Department of Environmental Health at the Harvard School of Public Health. TRIAL
      REGISTRATION NUMBER: N/A.

PMID- 25069505
TI  - Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced inflammasome
      activation in human gingival epithelial cells.
AB  - Interleukin-1beta (IL-1beta) is a pathogenic factor for the destruction of
      periodontal tissue in periodontitis. The processing of IL-1beta is regulated by
      cytosolic machinery termed as the inflammasome, which recruits and activates
      caspase-1 and then cleaves pro-IL-1beta to produce mature IL-1beta. Porphyromonas
      gingivalis (P. gingivalis) infection and lipopolysaccharide (LPS) have been shown
      to activate the NLRP3 inflammasome and stimulate IL-1beta production in human
      oral cells. Heme oxygenase-1 (HO-1) is an ubiquitous cytoprotective enzyme. The
      products of HO-1 exhibit protective biological activities, including antioxidant
      and anti-inflammatory effects. In the present study, we investigated the
      hypothesis that the induction of HO-1 inhibits the activation of the inflammasome
      and protects against LPS-induced inflammatory damage in cultured human gingival
      epithelial cells (GECs). Our results revealed that LPS induced the overexpression
      of the inflammasome components, NLRP3, apoptosis-associated speck-like protein
      containing a caspase recruitment domain (ASC) and caspase-1, by western blot
      analysis. Co-immunoprecipitation analysis indicated that LPS increased the
      binding of NLRP3 and ASC, and confocal imaging revealed that LPS increased the
      immunostaining and co-localization of ASC and caspase-1, indicating that LPS
      enhanced the assembly/formation of the inflammasome components. Hemin, a potent
      HO-1 inducer, blocked the LPS-induced overexpression and the formation of the
      NLRP3 inflammasome. Furthermore, hemin also inhibited the LPS-induced increase in
      the production of IL-1beta, as shown by enzyme-linked immunosorbent assay and
      blocked the nuclear translocation of pro-inflammatory nuclear factor-kappaB (NF
      kappaB), as shown by confocal assays. As a result, hemin protected the cells from
      LPS-induced damage, which was demonstrated by the immunostaining pattern of the
      cell junction protein, E-cadherin. LPS produced a disturbed staining pattern of E
      cadherin, suggesting the disruption of epithelial integrity, which was abolished
      in the hemin-treated cells. In conclusion, our data demonstrate that the
      induction of HO-1 by hemin attenuates LPS-induced inflammatory damage in human
      GECs through the inhibition of inflammasome activation. 

PMID- 25069506
TI  - Preface: MicroRNA: short but not small.

PMID- 25069507
TI  - Alternative polyadenylation and its impact on cellular processes.
AB  - Impact of mRNA processing and/or modifications has long been associated with gene
      expression regulation. Accumulating evidence shows alternative polyadenylation
      (APA), as an mRNA related process, to emerge as a widespread mechanism in gene
      expression regulation. Through selecting alternate (proximal or distal)
      polyadenylation signals on the 3'-UTR of pre-mRNAs, APA generates multiple
      transcript isoforms which may even create proteomic diversity. Depending on the
      use of proximal or distal polyadenylation sites, 3'-UTR lengths can vary in a
      tightly controlled manner in a spatial and temporal mode. Therefore, APA and its
      deregulation with potential consequences are highly relevant to normal and
      disease states. In this review, in light of recent findings in the literature,
      mechanism and types of APA and roles of APA in biological processes (i.e.
      proliferation, development, differentiation, and transformation) are discussed. 

PMID- 25069509
TI  - A focus on microfluidics and nanotechnology approaches for the ultra sensitive
      detection of microRNA.
AB  - MicroRNAs are small RNAs that are deregulated under disease conditions. This
      allows them to be used as biomarkers for disease diagnosis. Recently, such
      microRNAs are serving as non- invasive blood based biomarkers due to ease of
      detection, and high stability at room temperature in biofluids. In view of these
      advancements in biomarker research, efficient miRNA detection at the femtomolar
      level is important. MiRNA detection techniques to date include Northern blotting,
      real time PCR and microarray technology. While these are efficient techniques,
      they cannot detect very low miRNA levels, and have questionable specificity. This
      review describes nanotechnology, microfluidics and liquid phase miRNA detection
      techniques that are highly sensitive and specific. With some sophistication, some
      of these techniques can be used as point of care devices to rapidly detect low
      level miRNA in patient clinical samples to aid disease diagnosis and prognosis.

PMID- 25069510
TI  - Involvement of microRNA Mir15a in control of human ovarian granulosa cell
      proliferation, apoptosis, steroidogenesis, and response to FSH.
AB  - Our study aimed to examine the role of micro RNA Mir15a in control of basic
      ovarian cell functions: proliferation, apoptosis, and secretory activity. In the
      first series of experiments, primary human ovarian granulosa cells were
      transfected with antisense construct blocking Mir15a (anti-Mir15a) and cultured
      without hormonal treatments. Accumulation of markers of proliferation
      (MAPK/ERK1,2 and PCNA) and apoptosis (caspase 3 and bax), and release of steroid
      hormones (progesterone, testosterone, and estradiol) were evaluated by
      immunocytochemical analysis and by enzyme immunoassay. In the second series of
      experiments, granulosa cells were transfected with gene construct encoding Mir15a
      precursor (pre-Mir15a) and cultured with and without follicle-stimulating hormone
      (FSH; 0, 1, 10, and 100 ng/ml). Expression of markers of proliferation
      (MAPK/ERK1,2) apoptosis (caspase 3), and steroidogenesis (release of
      progesterone, testosterone, and estradiol) were evaluated. Transfection of cells
      with anti-Mir15a resulted in a significant increase in accumulation of both
      proliferation and apoptosis markers, a reduction in progesterone and testosterone
      release, and an increase in estradiol release. Transfection of cells with pre
      Mir15a had an opposite effect: it reduced accumulation of proliferation- and
      apoptosis-related proteins MAPK/ERK1,2 and caspase 3, and promoted release of
      progesterone and testosterone, but not estradiol. Moreover, pre-Mir15a reversed
      the effect of FSH on caspase 3, progesterone, and testosterone, but not on
      MAPK/ERK1,2 and estradiol. Our observations demonstrate involvement of Mir15a in
      control of multiple ovarian functions: proliferation, apoptosis, release of
      progesterone, androgen, and estrogen, and response to gonadotropin. Moreover,
      this is the first demonstration that miRNAs can affect response of cells to
      hormonal regulators. We propose that Mir15 could potentially be used for control
      of different reproductive processes. 

PMID- 25069511
TI  - Identification of critical microRNA gene targets in cervical cancer using network
      properties.
AB  - miRNAs are short non-coding RNAs which function as oncogenes or tumour suppressor
      gene and regulate gene expression by controlling targets that play role in cancer
      development and progression. Numerous recent studies have established an
      association of abnormal expression of miRNA with cervical cancer progression.
      Although the number of reported deregulated miRNA in cervical cancer is
      increasing, only a few associations between miRNA and their targets have been
      studied in cervical cancer. Therefore, we performed a systematic analysis of
      known dysregulated miRNAs involved in cervical cancer so as to identify critical
      miRNA targets that could pave way for therapeutic solutions. In this study,
      miRNAs reported to be dysregulated in cervical cancer were collected and their
      targets predicted using TargetScan, PicTar and miRanda. These targets were
      subsequently compared with previously curated gene dataset involved in cervical
      cancer to derive the putative target dataset. We then compared network properties
      (composed of degree, betweenness centrality, closeness centrality and clustering
      coefficient) of the putative, validated and human protein-protein interaction
      network. Based on the topological properties genes were ranked and observed that
      the gene targets BIRC5 (survivin), HOXA1 and RARB presenting with high Novoseek
      score of Genecards were enriched in cervical cancer. BIRC5 is an anti- apoptotic
      protein while HOXA1 and RARB are transcription factors which play critical role
      in altering the level of cell cycle and apoptosis associated proteins. Also,
      miRNA-mRNA network was constructed and it was found that miR-203 and miR-30b
      could target these genes. The analysis indicates that the genes BIRC5, HOXA1 and
      RARB are critical targets that play an important regulatory role in cervical
      cancer pathogenesis. 

PMID- 25069508
TI  - Regulation of miRNA processing and miRNA mediated gene repression in cancer.
AB  - The majority of human protein-coding genes are predicted to be targets of miRNA
      mediated post-transcriptional regulation. The widespread influence of miRNAs is
      illustrated by their essential roles in all biological processes. Regulated miRNA
      expression is essential for maintaining cellular differentiation; therefore
      alterations in miRNA expression patterns are associated with several diseases,
      including various cancers. High-throughput sequencing technologies revealed low
      level expressing miRNA isoforms, termed isomiRs. IsomiRs may differ in sequence,
      length, target preference and expression patterns from their parental miRNA and
      can arise from differences in miRNA biosynthesis, RNA editing, or SNPs inherent
      to the miRNA gene. The association between isomiR expression and disease
      progression is largely unknown. Misregulated miRNA expression is thought to
      contribute to the formation and/or progression of cancer. However, due to the
      diversity of targeted transcripts, miRNAs can function as both tumor-suppressor
      genes and oncogenes as defined by cellular context. Despite this, miRNA profiling
      studies concluded that the differential expression of particular miRNAs in
      diseased tissue could aid the diagnosis and treatment of some cancers. 

PMID- 25069513
TI  - The role of microRNAs in the pancreatic differentiation of pluripotent stem
      cells.
AB  - The generation of beta-cells in vitro is an attractive option for cell therapy
      treatments for type 1 diabetes and also for the development of more accurate
      disease models. A number of studies have demonstrated that insulin-expressing
      cells can be generated by the in vitro differentiation of human pluripotent stem
      cells. However, to date, these differentiation protocols are often inefficient,
      time-consuming and highly variable. In many cases, this is a result of an
      incomplete understanding of the regulatory processes involved in the
      differentiation of human pluripotent stem cells. One such process is the control
      of gene expression by microRNAs (miRNAs). Given that miRNAs have the potential to
      influence cell fate, we present in this short review the evidence that a further
      understanding of the role of miRNAs in pancreatic development and function may be
      important in the on-going quest to generate insulin-secreting cells from
      pluripotent stem cells. 

PMID- 25069514
TI  - Key roles of microRNA-22 family in complex organisms inferred from its evolution.
AB  - Previous studies suggested that microRNAs (miRNAs) participate in almost all
      cellular processes and the continuous development of miRNA-mediated
      posttranscriptional regulation might have facilitated the development of complex
      organisms. Especially, the microRNA-22 (miR-22) family has been recently
      extensively reported. Here, we accessed the evolution of miR-22 structure,
      regulation, and targets, and this indicated that miR-22 plays key roles in more
      complex organisms. We demonstrated that the miR-22 family arose approximate 600
      million years ago from the latest common ancestor of bilaterians. Moreover, a
      survey of genomic contexts and the secondary structure of the miR-22 family
      revealed that it originated de novo from a relatively conserved intron region,
      and the mature sequence of the miR-22 family evolved by seed pairing with highly
      conserved 3' "U" and 5' "G" boundaries. Furthermore, a complete picture of the
      evolution of the regulatory networks associated with miR-22 was obtained from the
      analysis of experimentally identified, as well as computationally predicted,
      functional targets of miR-22. 

PMID- 25069504
TI  - Assisted reproductive technology in Europe, 2010: results generated from European
      registers by ESHRE?.
AB  - STUDY QUESTION: The 14th European IVF--monitoring (EIM) report presents the
      results of medically assisted reproduction treatments including assisted
      reproductive technology (ART) cycles and intrauterine insemination (IUI) cycles
      initiated in Europe during 2010: are there changes in the trends compared with
      previous years? SUMMARY ANSWER: Despite some fluctuations in the number of
      countries reporting, the overall number of ART cycles has continued to increase
      year by year, and while pregnancy rates in 2010 remained similar to those
      reported in 2009, the number of transfers with multiple embryos (three or more)
      further declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been
      collected and reported in 13 manuscripts, published in Human Reproduction. STUDY
      DESIGN, SIZE, DURATION: Retrospective collection of European ART data by the EIM
      Consortium for ESHRE; data were collected from cycles started between 1st January
      and 31st December 2010 by the National Registries of individual European
      countries, or on a voluntary basis by personal information for European countries
      without a national registry. PARTICIPANTS/MATERIALS SETTING, METHODS: Out of 31
      countries, 991 clinics reported 550 296 ART treatment cycles: IVF (125 994), ICSI
      (272 771), frozen embryo replacement (FER, 114 593), egg donation (ED, 25 187),
      in vitro maturation (493), preimplantation genetic diagnosis/preimplantation
      genetic screening (6399) and frozen oocyte replacements (4859). European data on
      IUI using husband/partner's semen (IUI-H) or donor semen (IUI-D) were reported
      from 22 and 19 countries, respectively. A total of 176 512 IUI-H (+8.4% compared
      with 2009) and 38 124 IUI-D (+30.4% compared with 2009) cycles were included.
      MAIN RESULTS AND THE ROLE OF CHANCE: In 16 countries where all clinics reported
      to the national ART registry, a total of 267 120 ART cycles were performed in a
      population of 219 million inhabitants, corresponding to 1221 cycles per million
      inhabitants. For IVF, the clinical pregnancy rates per aspiration and per
      transfer increased to 29.2 and 33.2%, respectively, and for ICSI, the
      corresponding rates also increased to 28.8 and 32.0%, when compared with the
      rates of 2009. In FER cycles, the pregnancy rate per thawing was 20.3%; in ED
      cycles the pregnancy rate per fresh transfer was 47.4% and per thawed transfer
      33.3%. The delivery rate after IUI-H was 8.9 and 13.8% after IUI-D. In IVF and
      ICSI cycles, one, two, three and four or more embryos were transferred in 25.7,
      56.7, 16.1 and 1.5%, respectively. The proportions of singleton, twin and triplet
      deliveries after IVF and ICSI (combined) were 79.4, 19.6 and 1.0%, respectively,
      resulting in a total multiple delivery rate of 20.6% compared with 20.2% in 2009,
      21.7% in 2008, 22.3% in 2007, 20.8% in 2006. In FER cycles, the multiple delivery
      rate was 12.8% (12.5% twins and 0.3% triplets). Twin and triplet delivery rates
      associated with IUI cycles were 9.6/0.5 and 8.5/0.2%, following treatment with
      husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The
      method of reporting is not standardized in Europe but varies among countries.
      Furthermore registries from a number of countries have been unable to provide
      some of the relevant data such as initiated cycles and deliveries. Therefore,
      results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS:
      The 14th ESHRE report on ART and IUI treatments shows a continuing expansion of
      the number of ART treatment cycles in Europe, with more than half a million of
      cycles reported in 2010. The use of ICSI may have reached a plateau. When
      compared with 2009/2008, pregnancy and (multiple) delivery rates after IVF and
      ICSI remained relatively stable. The number of multiple embryo transfers (three
      or more embryos) has shown a decline. STUDY FUNDING/COMPETING INTERESTS: The
      study has no external funding; all costs are covered by ESHRE. There are no
      competing interests.

PMID- 25069512
TI  - MicroRNAs: modulators of cell identity, and their applications in tissue
      engineering.
AB  - MicroRNAs post-transcriptionally regulate the expression of approximately 60% of
      the mammalian genes, and have an important role in maintaining the differentiated
      state of somatic cells through the expression of unique tissuespecific microRNA
      sets. Likewise, the stemness of pluripotent cells is also sustained by embryonic
      stem cell-enriched microRNAs, which regulate genes involved in cell cycle, cell
      signaling and epigenetics, among others. Thus, microRNAs work as modulator
      molecules that ensure the appropriate expression profile of each cell type.
      Manipulation of microRNA expression might determine the cell fate. Indeed,
      microRNA-mediated reprogramming can change the differentiated status of somatic
      cells towards stemness or, conversely, microRNAs can also transform stem- into
      differentiated-cells both in vitro and in vivo. In this Review, we outline what
      is currently known in this field, focusing on the applications of microRNA in
      tissue engineering. 

PMID- 25069515
TI  - Interface engineering of a highly sensitive solution processed organic
      photodiode.
AB  - We report on tuning of the interfacial properties of a highly sensitive organic
      photodiode by introducing a buffer layer between the anode and the semiconductor
      layer. The effects of different buffer layers consisting of a self-assembled
      monolayer (SAM), PEDOT:PSS, and pentacene on the morphology and crystallinity of
      the upper-deposited bulk heterojunction semiconductor layer are carefully
      analyzed combined with electrical analysis. The active layer is controlled to be
      nearly homogeneous and to have low crystallinity by using a SAM or PEDOT:PSS
      buffer layers, whereas a highly crystalline morphology is realized by using the
      pentacene buffer layer. When exposed to light pulses, the external quantum
      efficiency and thus the photocurrent are slightly higher for the PEDOT:PSS-based
      photodiode; however the dark current is the lowest for the pentacene-based
      photodiode. We discuss the origin of the high sensitivity (a detectivity of 1.3 *
      10(12) Jones and a linear dynamic range of 95 dB) of the pentacene-based
      photodiode, particularly in terms of the morphology-driven low dark current. 

PMID- 25069517
TI  - Deuterated drugs: where are we now?
AB  - INTRODUCTION: Deuterated versions of existing drugs can exhibit improved
      pharmacokinetic or toxicological properties due the stronger deuterium- carbon
      bond modifying their metabolism. There is great interest in the current state of
      development of this approach. AREAS COVERED: This review covers recent US patent
      applications and prosecutions in this area that are based on beneficial
      modifications in metabolism of deuterated versions of existing drugs. The current
      state of 35 U.S.C. S103 'obviousness' rejections are emphasized, as is the
      development of strategies to overcome such rejections. Current trials and market
      considerations are also discussed. EXPERT OPINION: Deuterated drugs collectively
      are worth at least US$1 billion. It would seem that the likelihood of obviousness
      rejections is increasing in this area. However, careful elucidation of metabolic
      outcomes from deuteration that would not be anticipated from the prior art, and
      are instead unexpected and unobvious, has enabled allowance. Showing that drug
      deuteration alters pharmacokinetics by mechanisms not currently part of the prior
      art surrounding deuterated drugs has also been successful. Development of these
      and other strategies, combined with developing the extensive base of issued
      patents will enable the field to remain commercially attractive for some time.

PMID- 25069516
TI  - A novel anti-cancer effect of resveratrol: reversal of epithelial-mesenchymal
      transition in prostate cancer cells.
AB  - Carcinoma progression is associated with the loss of epithelial features and the
      acquisition of a mesenchymal phenotype, a process known as epithelial-mesenchymal
      transition (EMT). Resveratrol, a natural polyphenolic compound found in grapes,
      berries and peanuts, has a wide range of pharmacological properties, including
      anti-tumor metastasis properties. The underlying mechanism through which
      resveratrol inhibits metastasis of prostate cancer (PCa) is not yet fully
      understood; however, it is thought to be associated with the disruption of EMT.
      In the present study, lipopolysaccharide (LPS) was used to trigger EMT in PC-3
      and LNCaP PCa cell lines, and the cell lines were subsequently treated with
      resveratrol. The results demonstrated that exposure of PC-3 and LNCaP cells to
      LPS resulted in morphological alterations characteristic of EMT, as well as an
      increase in the expression of the mesenchymal marker vimentin and a decrease in
      the expression of E-cadherin. In addition, LPS exposure resulted in an increase
      in cell motility, along with an upregulation of the transcription factor glioma
      associated oncogene homolog 1 (Gli1). However, treatment with resveratrol
      inhibited LPS-induced morphological changes, decreased the expression of LPS
      induced markers of EMT and inhibited the expression of Gli1, resulting in the
      inhibition of in vitro cell motility and invasiveness. These results provide a
      novel perspective for the anti-invasion mechanism of resveratrol, suggesting that
      the effect is in part due to its ability to inhibit the EMT process through the
      Hedgehog signaling pathway.

PMID- 25069518
TI  - Oral health status and its impact on the quality of life of children and
      adolescents living with HIV-1.
AB  - BACKGROUND: Oral health problems can generate considerable negative effects on
      the quality of life of individuals living with HIV. The aim of this study was
      investigate the oral health status and its impact on the quality of life of 1 to
      18 years-old living with HIV-1 under follow-up at referral centers in Southern
      Brazil. METHODS: A cross-sectional study involving individuals under follow-up (n
      = 36) was carried out. The individuals living with HIV-1 and their guardians
      underwent individual interviews using validated questionnaires for assessing oral
      health-related quality of life according to age group. Clinical oral examinations
      were performed to establish oral health status, in terms of caries and treatment
      need, HIV-1-related gingival as well as stomatological changes. Medical records
      were reviewed searching for clinical history of the infection and the presence of
      HIV-1-related diseases. Association studies between frequent/very frequent oral
      health-related impact on quality of life and independent variables were performed
      using Fisher's exact test. RESULTS: The prevalence of frequent/very frequent oral
      health-related impact on quality of life was 69.0%. The prevalence of caries was
      75.9%. Gingival changes were present in 20.7% of the individuals. Dental
      treatment was needed in 72.4% of the patients. HIV-1-related disease was present
      in 55.2%. The variables significantly associated with the prevalence of
      frequent/very frequent impact on oral health-related quality of life were dental
      treatment need (p = 0.037) and being more than 12 years of age (p = 0.041).
      CONCLUSIONS: Individuals living with HIV-1 with need for dental treatment and
      those over 12-years of age reported a statistically higher frequency of
      frequent/very frequent oral health-related impact on quality of life.

PMID- 25069520
TI  - An efficient unsupervised fetal QRS complex detection from abdominal maternal
      ECG.
AB  - Non-invasive fetal heart rate is of great relevance in clinical practice to
      monitor fetal health state during pregnancy. To date, however, despite
      significant advances in the field of electrocardiography, the analysis of
      abdominal fetal ECG is considered a challenging problem for biomedical and signal
      processing communities. This is mainly due to the low signal-to-noise ratio of
      fetal ECG and difficulties in cancellation of maternal QRS complexes, motion and
      electromyographic artefacts. In this paper we present an efficient unsupervised
      algorithm for fetal QRS complex detection from abdominal multichannel signal
      recordings combining ICA and maternal ECG cancelling, which outperforms each
      single method. The signal is first pre-processed to remove impulsive artefacts,
      baseline wandering and power line interference. The following steps are then
      applied: maternal ECG extraction through independent component analysis (ICA);
      maternal QRS detection; maternal ECG cancelling through weighted singular value
      decomposition; enhancing of fetal ECG through ICA and fetal QRS detection. We
      participated in the Physionet/Computing in Cardiology Challenge 2013, obtaining
      the top official scores of the challenge (among 53 teams of participants) of
      event 1 and event 2 concerning fetal heart rate and fetal interbeat intervals
      estimation section. The developed algorithms are released as open-source on the
      Physionet website. 

PMID- 25069521
TI  - Evaluation of the kinetics and mechanism of action of anti-integration host
      factor-mediated disruption of bacterial biofilms.
AB  - The extracellular polymeric substance produced by many human pathogens during
      biofilm formation often contains extracellular DNA (eDNA). Strands of bacterial
      eDNA within the biofilm matrix can occur in a lattice-like network wherein a
      member of the DNABII family of DNA-binding proteins is positioned at the vertex
      of each crossed strand. To date, treatment of all biofilms tested with antibodies
      directed against one DNABII protein, Integration Host Factor (IHF), results in
      significant disruption. Here, using non-typeable Haemophilus influenzae as a
      model organism, we report that this effect was rapid, IHF-specific and mediated
      by binding of transiently dissociated IHF by anti-IHF even when physically
      separated from the biofilm by a nucleopore membrane. Further, biofilm disruption
      fostered killing of resident bacteria by previously ineffective antibiotics. We
      propose the mechanism of action to be the sequestration of IHF upon dissociation
      from the biofilm eDNA, forcing an equilibrium shift and ultimately, collapse of
      the biofilm. Further, antibodies against a peptide positioned at the DNA-binding
      tips of IHF were as effective as antibodies directed against the native protein.
      As incorporating eDNA and associated DNABII proteins is a common strategy for
      biofilms formed by multiple human pathogens, this novel therapeutic approach is
      likely to have broad utility. 

PMID- 25069522
TI  - Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis
      with intravenous recombinant tissue plasminogen activator: a review of natural
      history and treatment.
AB  - IMPORTANCE: Intravenous thrombolysis remains the mainstay treatment for acute
      ischemic stroke. One of the most feared complications of the treatment is
      thrombolysis-related symptomatic intracerebral hemorrhage (sICH), which occurs in
      nearly 6% of patients and carries close to 50% mortality. The treatment options
      for sICH are based on small case series and expert opinion, and the efficacy of
      recommended treatments is not well known. OBJECTIVE: To provide an overview on
      the rationale and mechanism of action of potential treatments for sICH that may
      reverse the coagulopathy before hematoma expansion occurs. EVIDENCE REVIEW:
      Evidence-based peer-reviewed articles, including randomized trials, case series
      and reports, and retrospective reviews, were identified in a PubMed search on the
      mechanism of action of intravenous recombinant tissue plasminogen activator and
      the rationale of various potential treatments using the coagulation cascade as a
      model. The search encompassed articles published from January 1, 1990, through
      February 28, 2014. FINDINGS: The current treatments may not be sufficient to
      reverse coagulopathy early enough to prevent hematoma expansion and improve the
      outcome of thrombolysis-related hemorrhage. CONCLUSIONS AND RELEVANCE: Given the
      mechanism of action of intravenous recombinant tissue plasminogen activator,
      clinical studies could include agents with a fast onset of action, such as
      prothrombin complex concentrate, recombinant factor VIIa, and epsilon
      aminocaproic acid, as potential therapeutic options.

PMID- 25069524
TI  - Clinical differences between early- and late-onset psoriasis in Thai patients.
AB  - OBJECTIVES: There is a paucity of data regarding clinical differences between
      early-onset psoriasis (EOP) and late-onset psoriasis (LOP) in Asian populations.
      This study aimed to investigate clinical differences between EOP (onset at the
      age of <40 years) and LOP (onset at the age of >=40 years) in Thai patients.
      METHODS: From 2002 until 2008, staff and residents in the Department of
      Dermatology, Siriraj Hospital, were asked to complete a questionnaire detailing
      the age of onset, family history of psoriasis, comorbid diseases, clinical
      features, nail and joint involvement, and severity of psoriasis in all psoriasis
      patients. Data were analyzed using descriptive statistics and chi-squared tests.
      RESULTS: A total of 1017 patients were enrolled. Of these, 663 (65.2%) patients
      had EOP and 354 (34.8%) had LOP. The mean +/- standard deviation age of onset was
      24.8 +/- 8.7 years in the EOP group and 51.6 +/- 9.6 years in the LOP group. The
      two most common comorbid diseases were hypertension and diabetes mellitus in both
      groups. Patients with EOP had a significantly higher likelihood of both a family
      history of disease and guttate psoriasis. Palmoplantar psoriasis was more
      commonly found in LOP patients. Nail and joint involvement and disease severity
      were not associated significantly with age of onset. CONCLUSIONS: The present
      study supports the hypothesis that there are clinical differences between EOP and
      LOP in Asian populations.

PMID- 25069525
TI  - Reasons for female neonaticide in India.

PMID- 25069523
TI  - Transcranial magnetic stimulation in the treatment of substance addiction.
AB  - Transcranial magnetic stimulation (TMS) is a noninvasive method of brain
      stimulation used to treat a variety of neuropsychiatric disorders, but is still
      in the early stages of study as addiction treatment. We identified 19 human
      studies using repetitive TMS (rTMS) to manipulate drug craving or use, which
      exposed a total of 316 adults to active rTMS. Nine studies involved tobacco, six
      alcohol, three cocaine, and one methamphetamine. The majority of studies targeted
      high-frequency (5-20 Hz; expected to stimulate neuronal activity) rTMS pulses to
      the dorsolateral prefrontal cortex. Only five studies were controlled clinical
      trials: two of four nicotine trials found decreased cigarette smoking; the
      cocaine trial found decreased cocaine use. Many aspects of optimal treatment
      remain unknown, including rTMS parameters, duration of treatment, relationship to
      cue-induced craving, and concomitant treatment. The mechanisms of rTMS potential
      therapeutic action in treating addictions are poorly understood, but may involve
      increased dopamine and glutamate function in corticomesolimbic brain circuits and
      modulation of neural activity in brain circuits that mediate cognitive processes
      relevant to addiction, such as response inhibition, selective attention, and
      reactivity to drug-associated cues. rTMS treatment of addiction must be
      considered experimental at this time, but appears to have a promising future. 

PMID- 25069526
TI  - IL-17A induces hypo-contraction of intestinal smooth muscle via induction of iNOS
      in muscularis macrophages.
AB  - Intestinal inflammation causes disorder in bowel motility. Th17 cytokines are
      involved in intestinal inflammation. To understand the role of interleukin (IL)
      17 in intestinal motility, we examined effects of IL-17A on contractile
      activities of organ-cultured ileum. Rat ileal smooth muscle strips were organ
      cultured with IL-17A. Muscle contraction was measured, and cells expressing
      inducible nitric oxide synthase (iNOS) were identified with immunohistochemistry.
      Creating Th17-transferred colitis model mice, in vivo effects of IL-17 on
      contractile activities, and iNOS mRNA expression in colonic smooth muscle were
      investigated. Treatment with IL-17A for 12 h and 3 days attenuated carbachol- and
      membrane depolarization-induced contractions in organ-cultured rat ileum. N(G)
      Nitro-l-arginine methyl ester (100 MUM), a nitric oxide synthase inhibitor,
      completely reversed the IL-17A-induced inhibition of contractile force. Ileal
      tissue cultured in the presence of IL-17A showed increased expression of iNOS
      mRNA and protein. Immunohistochemical analysis using an iNOS antibody revealed
      that iNOS protein was expressed on ED2-positive muscularis macrophages. The level
      of iNOS mRNA was also increased in inflamed colonic smooth muscle of Th17
      transferred colitis model mice. In intestinal inflammation, IL-17A induces an
      intestinal motility disorder through iNOS expression in muscularis macrophages. 

PMID- 25069527
TI  - Screening for skin cancer in bank and insurance employees: risk profile and
      correlation of self and physician's assessment.
AB  - BACKGROUND: Self-assessment and knowledge of individual risk factors can be a
      reasonable strategy to detect cutaneous malignancies in an early curable stage.
      METHODS: Bank and insurance employees were voluntarily screened for skin cancer.
      They had to fill in a questionnaire asking for their skin and hair color,
      ultraviolet exposure and tanning ability, number and size of typical and atypical
      nevi, immunosuppression or chemotherapy, and history of skin cancer. Afterwards
      dermatologists performed a whole body evaluation, including a total body nevi
      count, and calculated an individualized risk profile. RESULTS: A total of 1658
      employees were evaluated. Most employees underestimated their total number of
      nevi. There was poor agreement between employees and dermatologists (weighted
      kappa-value = 0.03); 45.5% of the employees were judged to be at low risk, 27.3%
      as intermediate risk, and 27.2% as high risk. Twenty-seven employees (3.7%) with
      suspicious lesions were transferred to the clinics for further evaluation.
      CONCLUSION: Screening for skin cancer in a working population reveals low numbers
      of suspicious lesions. The focus of mass screenings should be on education and
      teaching of self-examinations.

PMID- 25069528
TI  - Application of the Occupational Sitting and Physical Activity Questionnaire
      (OSPAQ) to office based workers.
AB  - BACKGROUND: The workplace is a setting where sedentary behaviour is highly
      prevalent. Accurately measuring physical activity and sedentary behaviour is
      crucial to assess the impact of behavioural change interventions. This study
      aimed to evaluate the reliability and criterion validity of the Occupational
      Sitting and Physical Activity Questionnaire (OSPAQ) and compare with data
      collected by accelerometers. METHODS: A test-retest study was undertaken on 99
      participants using the OSPAQ. Data were then compared to accelerometer records of
      41 participants. Reliability was assessed by paired t-test and intra-class
      correlations (ICC) via a two-way mixed model based on absolute agreement.
      Difference and agreement were measured by comparison of mean self-reported data
      with accelerometer data using the Pearson's correlation coefficient and Bland
      Altman plots. RESULTS: The ICCs for minutes spent sitting (0.66), standing (0.83)
      and walking (0.77) showed moderate to strong test-retest reliability. No
      significant differences were found between the repeated measurements taken seven
      days apart. Correlations with the accelerometer readings were moderate. The Bland
      Altman plots showed moderate agreement for standing time and walking time but
      systematic variation for sedentary time. CONCLUSION: The OSPAQ appears to have
      acceptable reliability and validity measurement properties for application in the
      office workplace setting.

PMID- 25069529
TI  - Predicting institutional long-term care admission in dementia: a mixed-methods
      study of informal caregivers' reports.
AB  - AIM: To investigate agreement between: (1) expected reasons and actual reasons
      for admission of people with dementia according to informal caregivers; (2)
      scores on measurement instruments prior to admission and the actual reasons for
      admission according to informal caregivers. BACKGROUND: Timely admission of
      people with dementia is a crucial issue. Information is highly warranted on
      whether informal caregivers are capable of prior identification of causes of
      admission and, can thus be considered a reliable prospective source on causes of
      admission. DESIGN: A cohort study among informal caregivers of people with
      dementia who made a transition to institutional long-term care. METHODS:
      Qualitative data on the expected and actual reasons for admission were collected
      via open-ended questions at baseline and follow-up. Furthermore, at baseline,
      data were collected using measurement instruments to measure pre-admission
      characteristics. Interviews took place between November 2010-April 2012. After
      categorizing the answers, the agreement between the expected and actual reasons
      was calculated. Furthermore, bivariate associations were calculated between the
      actual reasons for admission and scores on corresponding measurement instruments.
      RESULTS/FINDINGS: For most informal caregivers, there was agreement between their
      statements on the expected reason and the actual reason for admission. A third of
      the caregivers showed no conformity. Bivariate associations showed that there is
      also agreement between the actual reasons for admission and scores on
      corresponding measurement instruments. CONCLUSION: Informal caregivers can be
      considered reliable sources of information regarding what causes the admission of
      a person with dementia. Professional care should anticipate informal caregivers'
      statements and collaborate with them to strive for timely and appropriate
      admission.

PMID- 25069531
TI  - Metoclopramide for patients with intractable hiccups: a multicentre, randomised,
      controlled pilot study.
AB  - BACKGROUND: Limited data exist regarding the efficacy of metoclopramide in the
      treatment of intractable hiccups. AIM: This study aimed to assess the feasibility
      efficacy of metoclopramide in the treatment of patients with intractable hiccups.
      METHODS: A total of 36 patients with intractable hiccups was randomly assigned to
      arm A (n = 18) or arm B (n = 18) in a multicentre, double-blind, randomised,
      controlled pilot study. Participants in arm A received 10-mg metoclopramide
      thrice daily for 15 days, whereas those assigned to arm B received 10-mg placebo
      thrice daily for 15 days. The primary outcome measure was total efficacy against
      hiccups (including cessation and improvement of hiccups). Secondary outcome
      measures included a comparison of overall efficacy and adverse events between the
      two arms. RESULTS: Of the 36 patients enrolled, 34 participants completed the
      study. The total efficacy was higher in arm A than in arm B (relative risk, 2.75;
      95% confidence interval: 1.09-6.94, P = 0.03). Furthermore, comparison between
      the two arms revealed that overall efficacy was higher in arm A than that in arm
      B (P < 0.05). No serious adverse events related to the treatment were documented
      in either arm. The most common adverse events occurring in patients in arm A
      included fatigue, upset mood and dizziness. CONCLUSION: Metoclopramide appears to
      be a promising candidate for the treatment of patients with intractable hiccups,
      with mild adverse events. However, further clinical trials are required to
      confirm these results.

PMID- 25069530
TI  - A review of the effects of artemether-lumefantrine on gametocyte carriage and
      disease transmission.
AB  - While significant advances have been made in the prevention and treatment of
      malaria in recent years, these successes continue to fall short of the World
      Health Organization (WHO) goals for malaria control and elimination. For
      elimination strategies to be effective, limited disease transmission, achieved
      through rapid reduction in the infectious parasite reservoir and decreased
      gametocyte carriage, will be critical. Artemisinin-based combination therapy
      (ACT) forms the cornerstone of WHO-recommended treatment for uncomplicated
      Plasmodium falciparum malaria, and in combination with other effective
      interventions will undoubtedly play a vital role in elimination programmes. The
      gametocytocidal properties of artemisinins are a bonus attribute; there is
      epidemiological evidence of reductions in malaria incidence and transmission in
      African regions since the introduction of these agents. Many studies and analyses
      have specifically investigated the effects of the ACT, artemether-lumefantrine
      (AL) on gametocyte carriage. In this systematic review of 62 articles published
      between 1998 and January 2014, the effects of AL on gametocyte carriage and
      malaria transmission are compared with other artemisinin-based anti-malarials and
      non-ACT. The impact of AL treatment of asymptomatic carriers on population
      gametocyte carriage, and the potential future role of AL in malaria elimination
      initiatives are also considered. Despite the inherent difficulties in comparing
      data from a range of different studies that also utilized different diagnostic
      approaches to assess baseline gametocyte counts, the gametocytocidal effect of AL
      was proportionately consistent across the studies reviewed, suggesting that AL
      will continue to play a vital role in the treatment of malaria and contribute to
      clearing the path towards malaria elimination. However, the specific place of AL
      is the subject of much ongoing research and will undoubtedly be dependent on
      different demographic and geographical scenarios. Utilizing ACT, such as AL,
      within malaria elimination strategies is also associated with a number of other
      challenges, such as balancing potential increased use of ACT (e g, treatment of
      asymptomatic carriers and home-based treatment) with rational use and avoidance
      of drug resistance development. 

PMID- 25069532
TI  - The possibilities and limitations of forensic hand comparison.
AB  - On recordings of certain crimes, the face is not always shown. In such cases,
      hands can offer a solution, if they are completely visible. An important aspect
      of this study was to develop a method for hand comparison. The research method
      was based on the morphology, anthropometry, and biometry of hands. A new aspect
      of this study was that a manual and automated test were applied, which,
      respectively, assess many features and provide identification rates quickly. An
      important observation was that good quality images can provide sufficient hand
      details. The most distinctive features were the length/width ratio, the palm line
      pattern and the quantity of highly distinctive features present, and how they are
      distributed. The results indicate that experience did not improve the
      identification rates, while the manual test did. Intra-observer variability did
      not influence the results, whereas hands of relatives were frequently misjudged.
      Both tests provided high identification rates. 

PMID- 25069533
TI  - Group V secretory phospholipase A2 impairs endothelial protein C receptor
      dependent protein C activation and accelerates thrombosis in vivo.
AB  - BACKGROUND: Endothelial protein C receptor (EPCR) must be bound to a molecule of
      phosphatidylcholine (PC) to be fully functional, i.e. to interact with protein
      C/activated protein C (APC) properly. PC can be replaced with other lipids, such
      as lysophosphatidylcholine or platelet-activating factor, by the action of group
      V secretory phospholipase A2 (sPLA2-V), an enzyme that is upregulated in a
      variety of inflammatory conditions. Studies in purified systems have demonstrated
      that the substitution of PC notably impairs EPCR function in a process called
      EPCR encryption. OBJECTIVES: To analyze whether sPLA2-V was able to regulate EPCR
      dependent protein C activation in vivo, and its impact on thrombosis and the
      hemostatic system. METHODS: Mice were transfected with sPLA2-V by hydrodynamic
      gene delivery. The effects on thrombosis were studied with the laser carotid
      artery occlusion model, and APC generation capacity was measured with ELISA.
      Global hemostasis was analyzed with thromboelastometry. RESULTS: We found that
      sPLA2-V overexpression in mice significantly decreased their ability to generate
      APC. Furthermore, a murine carotid artery laser thrombosis model revealed that
      higher sPLA2-V levels were directly associated with faster artery thrombosis.
      CONCLUSIONS: sPLA2-V plays a thrombogenic role by impairing the ability of EPCR
      to promote protein C activation.

PMID- 25069534
TI  - 'At the right time, in the right way, with the right resources': perceptions of
      the quality of care provided during childbirth in Malawi.
AB  - BACKGROUND: Improving the quality of care women receive during childbirth is as
      important as ensuring increased availability of care and numbers of healthcare
      providers. To be able to improve quality of care, it is important to understand
      what quality means for mothers as well as providers of care. METHODS: 33
      postnatal mothers and 10 healthcare providers from all 4 major hospitals in one
      district in Malawi were interviewed via 27 in-depth interviews and 2 focus group
      discussions. Data was transcribed and analysed using the thematic framework
      approach. RESULTS: Perceptions of quality of care differed substantially between
      care providers and postnatal mothers. For caregivers, characteristics of good
      quality care included availability of resources while for postnatal mothers
      positive relationships with their caregiver were important. Lack of autonomy and
      decision making power is a barrier to quality of care and it exists both at the
      level of the patient (mother) and at the level of her caregiver with healthcare
      providers unable to influence decisions made by more senior staff or management.
      Lack of autonomy was linked with the emerging themes of staff de-motivation,
      frustration, lack of empowerment to make change and resulting in a poor quality
      of care provided. CONCLUSIONS: Creating a reciprocal understanding of what good
      quality care comprises and the barriers as well as promoters of this should be
      the starting point for improving the quality of maternity care. A renewed focus
      is needed on improving communication, strengthening patient rights and autonomy
      whilst simultaneously motivating and enabling healthcare workers to provide
      comprehensive and inclusive quality of care.

PMID- 25069535
TI  - DPP4 inhibitors increase differentially the expression of surfactant proteins in
      Fischer 344 rats.
AB  - AIM: Intact surface active agent (surfactant) composed of surfactant-associated
      proteins (SPs) and lipids is necessary for respiration and prevents alveoli from
      collapsing. CD26, a transmembrane glycoprotein exerting dipeptidyl peptidase
      activity (DPP4), highly expressed in lung parenchyma, is involved in inflammatory
      processes. A pharmacological inhibition of DPP4 influenced not only the
      inflammation but also elevated the SPs. Thus, DPP4 inhibitors may be a novel drug
      for treatment of diseases with surfactant deficiency. Therefore, we tested
      firstly the hypothesis that DPP4 inhibitors increase the expression of SPs in
      healthy rats. METHODS: SP mRNA and protein expression were determined different
      times after nebulization of aerosolized DPP4 inhibitors [L-isoleucine
      thiazolidide (L-Ile-Thia), L-valine-pyrrolidide (L-Val-Pyrr)], budesonide, saline
      or stereoisomers. RESULTS: Compared with negative controls (1) L-Ile-Thia as well
      as budesonide led to a significant higher and L-Val-Pyrr had the tendency to a
      significant higher expression of SP-A mRNA 6 h after nebulization, (2) the
      expression of SP-D mRNA increased significantly 6 h after nebulization with L-Ile
      Thia and 3 and 6 h after nebulization with Val-pyrr, (3) SP-B mRNA levels showed
      significantly higher values 3 and 6 h after nebulization with L-Val-Pyrr, (4)
      protein levels of SP-A, SP-B and SP-C were elevated significantly 6 h after
      nebulization with L-Val-Pyrr as well as with budesonide, and (5) phospholipids
      were also increased in response to DPP4 inhibition; the minimal surface tension
      was comparable. CONCLUSION: DPP4 inhibition influence differently the expression
      of surfactant proteins in healthy rats and may be suitable to elevate surfactant
      synthesis in different diseases accompanied with surfactant deficiencies.

PMID- 25069536
TI  - Anesthetic agents in patients with very long-chain acyl-coenzyme A dehydrogenase
      deficiency: a literature review.
AB  - Very long-chain acyl-coenzyme A dehydrongenase deficiency (VLCADD) is a rare
      disorder of fatty acid metabolism that renders sufferers susceptible to
      hypoglycemia, liver failure, cardiomyopathy, and rhabdomyolysis. The literature
      about the management of these patients is hugely conflicting, suggesting that
      both propofol and volatile anesthesia should be avoided. We have reviewed the
      literature and have concluded that the source papers do not support the
      statements that volatile anesthetic agents are unsafe. The reports on
      rhabdomyolysis secondary to anesthesia appear to be due to inadequate supply of
      carbohydrate not volatile agents. Catabolism must be avoided with minimal
      fasting, glucose infusions based on age and weight, and attenuation of emotional
      and physical stress. General anesthesia appears to be protective of stress
      induced catabolism and may offer benefits in children and anxious patients over
      regional anesthesia. Propofol has not been demonstrated to be harmful in VLCADD
      but is presented in an emulsion containing very long-chain fatty acids which can
      cause organ lipidosis and itself can inhibit mitochondrial fatty acid metabolism.
      It is therefore not recommended. Suxamethonium-induced myalgia may mimic symptoms
      of rhabdomyolysis and cause raised CK therefore should be avoided. Opioids,
      NSAIDS, regional anesthesia, and local anesthetic techniques have all been used
      without complication. 

PMID- 25069537
TI  - Improving communication outcomes for young offenders: a proposed response to
      intervention framework.
AB  - BACKGROUND: Speech, language and communication needs (SLCN) are strongly
      overrepresented in young offender populations, and there is growing commitment
      internationally to ensuring access to speech-language therapy services for such
      young people. However there is currently no framework in which such interventions
      might be conceptualized, delivered and evaluated. This is significant given the
      role of language competence in the development of prosocial skills and also in
      the transition to literacy. AIMS: To present Response to Intervention (RTI) as a
      framework in which SLCN of young offenders might be systematically addressed and
      evaluated within youth justice settings, led by speech-language therapists, in
      conjunction with other education and welfare team members. METHODS & PROCEDURES:
      Literature regarding prevalence rates of SLCN in young offenders is reviewed,
      together with the limited extant evidence on interventions for this group. The
      importance of applying evidence-based interventions is argued, and a framework
      for adapting RTI for SLCN in custodial settings is outlined. MAIN CONTRIBUTION: A
      framework for adapting RTI to design, deliver and evaluate speech-language
      therapy interventions in youth custodial settings is presented. CONCLUSIONS:
      Speech-language therapy interventions for young offenders will be better
      addressed at policy, practice and research levels if a framework such as an RTI
      adaptation is employed. It is expected, however, that this model will evolve over
      time, as intervention evidence pertaining to the youth offender population
      emerges.

PMID- 25069538
TI  - High ALDHdim-expressing CD34+CD38- cells in leukapheresed peripheral blood is a
      reliable guide for a successful leukemic xenograft model of acute myeloid
      leukemia.
AB  - The primary human acute myeloid leukemia (AML) cell injection xenograft mouse
      model is used to investigate multimodal therapies and drug screening on tumor
      growth. Since xenograft models using human cell lines to examine drug response
      are not correlated with the clinical outcomes observed in patients, a xenograft
      model using primary human cells has been used as a more appropriate model with
      which to minimize this problem. Although bone marrow (BM) cells from patients are
      often regarded as superior sources to establish xenograft models due to the high
      frequency of stem cell populations, there is a fatal drawback; only small volumes
      can be obtained and used for the generation of the leukemic xenograft model.
      Indeed, longevity of AML characteristics, as well as sufficient stem cells in the
      xenograft model, should be guaranteed to analyze the therapeutic response to a
      drug. Therefore, we examined whether leukapheresed peripheral blood (LPB)
      consists of reliable leukemic stem cells (LSCs) and ALDHdim-expressing CD34+CD38-
      cells, and functions in grafting human AML with virulence compared to that of BM.
      LPB cells showed an advantage for the xenograft mouse model with AML cell homing,
      engraftment and a high human ALDHdim-expressing CD34+CD38- cell population,
      suggesting an alternative cell source to BM. Overall, this xenograft model using
      LPB offers the possibility of overcoming the small volume limitation of BM and
      prevents individual variation by using a single LPB sample. This result is
      noteworthy in identifying cell sources capable of generating a stable xenograft
      model. 

PMID- 25069539
TI  - Re: Tramadol can selectively manage moderate pain in children following European
      advice limiting codeine use.

PMID- 25069540
TI  - Decision-making process in patients with lumbar spinal canal stenosis.
AB  - BACKGROUND: The aim of this study was to develop a strategy to determine a sound
      methodology for decision-making in lumbar spinal canal stenosis (LSCS). METHODS:
      This was a retrospective study of patients with LSCS to determine the rationale
      for those who underwent surgery and those who received conservative treatment.
      All case records were assessed to extract information on the morphology grade and
      dural sac cross-sectional surface area (DSCA) on MRI. Patients' functionality and
      satisfaction were examined as outcome measures in order to understand factors
      that were associated with benefit from either treatment strategy. RESULTS: In all
      357 patients, case records were reviewed. The mean age of patients was 57.5
      (SD=10.9) years. Of these, 176 patients underwent surgery. Post-treatment
      satisfaction was found in a large portion of the surgical group (93.2%) whereas
      this was 84.5% for those who received conservative treatment. Most patients
      (86.4%) who underwent surgery were identified as having grade C and grade D
      stenosis, while those who received conservative treatment were identified as
      having grade A and grade B stenosis (P<0.01). Overall satisfaction with surgery
      was found to be higher among patients with grade D stenosis (95%). Satisfaction
      by cross-sectional surface area did not show a consistent pattern. However, those
      with a cross-sectional surface area less than 100 mm2 benefited more from
      surgery. According to the findings, a decision matrix was proposed. CONCLUSIONS:
      The findings suggest that the morphological grade and the DSCA jointly are useful
      parameters for helping clinicians to make clinically sound decisions in LSCS
      patients.

PMID- 25069541
TI  - Independent predictors of shunt-dependent normal pressure hydrocephalus after
      aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Normal pressure hydrocephalus frequently develops after subarachnoid
      hemorrhage. It can often be difficult, however, to predict shunt dependency. The
      purpose of this study was to identify predictors of shunt-dependent normal
      pressure hydrocephalus (SDNPH) after aneurysmal subarachnoid hemorrhage (aSAH).
      METHODS: The incidence of SDNPH in 139 consecutive patients who underwent surgery
      for aSAH in the Department of Neurosurgery Tokyo Medical and Dental University
      between January 2008 and December 2011 was evaluated. The patientage, Glasgow
      Coma Score, World Federation of Neurosurgical Societies grade, Hunt and Hess
      grade, modified Fisher group, modified Rankin Scale, duration of external
      drainage of cerebrospinal fluid (CSF), gender, aneurysm location, presence of
      intraventricular hemorrhage, surgical method (clip or coil), and presence of
      acute hydrocephalus were analyzed. RESULTS: Forty-seven of 139 patients (33.8%)
      underwent shunt operation. Fifteen of these 47 patients were assessed to have
      high-pressure hydrocephalus and excluded. Thirty-two SDNPH patients (23.0%) were
      compared with 84 patients without hydrocephalus (60.4%). An age of 65 years or
      over (OR 5.51;95%CI 1.97-15.40), a GCS of 13 or less (OR 3.82;95%CI 1.38-10.60),
      and CSF drainage for a duration of 12 days or more (OR 3.63;95%CI 1.30-10.14)
      were independently associated with SDNPH. CONCLUSIONS: SDNPH after aSAH in our
      study showed no correlations with three of the parameters previously identified
      as risk factors for shunt-dependent hydrocephalus, namely, the amount of SAH, the
      presence of IVH, or acute hydrocephalus. Instead, a longer duration of CSF
      drainage correlated with SDNPH as an independent factor. These data suggest that
      a longer duration of CSF drainage may be one of the risk factors for SDNPH after
      aSAH.

PMID- 25069542
TI  - Surgery. NSAIDs and risk of anastomotic leaks after colorectal surgery.
AB  - NSAIDs provide improved pain control and reduce the use of opioids--both
      important components of enhanced recovery programs after colorectal surgery.
      However, the possible association between NSAID use and anastomotic leaks is
      greatly debated. Anastomotic leak remains an important concern due to the
      substantial associated morbidity.

PMID- 25069543
TI  - IBD. Specific genetic and microbial signature associated with paediatric ileal
      Crohn's disease.

PMID- 25069544
TI  - Diagnosis of IBS: symptoms, symptom-based criteria, biomarkers or
      'psychomarkers'?
AB  - IBS is estimated to have a prevalence of up to 20% in Western populations and
      results in substantial costs to health-care services worldwide, estimated to be
      US$1 billion per year in the USA. IBS remains difficult to diagnose due to its
      multifactorial aetiology, heterogeneous nature and overlap of symptoms with
      organic pathologies, such as coeliac disease and IBD. As a result, IBS often
      continues to be a diagnosis of exclusion, resulting in unnecessary
      investigations. Available methods for the diagnosis of IBS-including the current
      gold standard, the Rome III criteria-perform only moderately well. Visceral
      hypersensitivity and altered pain perception do not discriminate between IBS and
      other functional gastrointestinal diseases or health with any great accuracy.
      Attention has now turned to developing novel biomarkers and using psychological
      markers (so-called psychomarkers) to aid the diagnosis of IBS. This Review
      describes how useful symptoms, symptom-based criteria, biomarkers and
      psychomarkers, and indeed combinations of all these approaches, are in the
      diagnosis of IBS. Future directions in diagnosing IBS could include combining
      demographic data, gastrointestinal symptoms, biomarkers and psychomarkers using
      statistical methods. Latent class analysis to distinguish between IBS and non-IBS
      symptom profiles might also represent a promising avenue for future research. 

PMID- 25069545
TI  - Oesophagus. Genome-wide association study reveals the tissue-specific nature of
      eosinophilic oesophagitis.

PMID- 25069546
TI  - Intestinal tract. Patient-derived intestinal spheroids--culturing the gut.

PMID- 25069547
TI  - Person-based contextual therapy applied to a complex case of schizophrenia.
AB  - BACKGROUND: Psychological therapies are becoming more and more important in
      schizophrenia, and not as mere adjuncts to medication. The psychotherapy of
      schizophrenia is taking on a new lease of life in the wake of person-based
      phenomenological and psychological developments. METHOD: The case in question was
      a complex one, with variegated symptomatology that had persisted over many years.
      Approaching the case from the perspective of person-based cognitive therapy
      allowed us to understand the psychotic symptoms in the biographical context and
      to apply a therapy focused on the patient's recovery of her sense of self and of
      life. RESULTS: At the end of the therapy and throughout the 12-month follow-up,
      the psychotic experiences had practically disappeared, or ceased to be
      disturbing, and the patient had become re-integrated in social life. CONCLUSIONS:
      Psychotic symptoms take on meaning in the biographical context. Adopting this
      perspective can aid the psychopathological explanation of the disorder and
      provide significant therapeutic help, more focused on recovery. Psychological
      therapy has shown itself to be viable in complex cases treated within the public
      sector healthcare context.

PMID- 25069548
TI  - The Spanish version of the Believability of Anxious Feelings and Thoughts
      Questionnaire.
AB  - BACKGROUND: Cognitive fusion is suggested to play an important role in the
      etiology and maintenance of anxiety disorders according to Acceptance and
      Commitment Therapy. This study presents the psychometric data of the Spanish
      version of a cognitive fusion measure in the context of anxiety: the
      Believability of Anxious Feelings and Thoughts Questionnaire (BAFT). METHOD:
      First, we back-translated the BAFT into Spanish and then, administered it to
      three samples, with a total of 598 participants, in addition to other relevant
      anxiety measures. RESULTS: Data were very similar to those obtained with the
      original BAFT version. The BAFT showed a very good internal consistency (overall
      &alpha;= .92) and a hierarchical factor structure with two lower-order factors
      and one hierarchical factor. Participants showing mild levels of anxiety symptoms
      scored higher on the BAFT than participants who scored below the cutoffs. BAFT
      scores were significantly related to anxiety symptoms and to measures of
      psychological inflexibility, anxiety sensitivity, and mindfulness facets.
      Moreover, the BAFT showed incremental validity relative to anxiety sensitivity.
      CONCLUSIONS: This Spanish version of the BAFT emerges as a reliable and valid
      measure of cognitive fusion with anxious thoughts and feelings.

PMID- 25069549
TI  - The influence of the parents' educational level and participants' age in the
      derivation of equivalence-equivalence.
AB  - BACKGROUND: The objective of this work was the study of analogical reasoning from
      the perspective of the equivalence-equivalence phenomenon. METHOD: The variables
      studied consisted of the age of the participants and the educational level of the
      parents, in relation to performance on a reasoning task. The task utilized a
      sample size of 64 participants and an instrument based on conditional
      discriminations using the matching-to-sample procedure. RESULTS: The results
      showed a significant difference in the performance on the task between the
      children of parents with college degrees, and those of parents without college
      degrees. However, there were no conclusive results as to age. CONCLUSIONS: The
      results are analyzed from the perspective of the derivation of the relationship
      of equivalence-equivalence via multiple exemplar training.

PMID- 25069550
TI  - Spanish validation of the Family Questionnaire (FQ) in families of patients with
      an eating disorder.
AB  - BACKGROUND: The objective of this study is to evaluate the psychometric
      properties of the Spanish version of the Family Questionnaire (FQ) and to further
      examine the differences between mothers' and fathers' emotional response to an
      eating disorder (ED). METHOD: A total of 382 carers of patients with an ED
      participated in the study, with ages ranging from forty to fifty-three years old.
      RESULTS: The use of confirmatory factor analysis according to gender supported
      both factor models of the FQ, with only minor differences in comparison to the
      original study performed in 2002 by Wiedemann and collegues. The internal
      consistency of the Spanish version of the FQ was good. Mothers displayed
      significantly higher levels of emotional over-involvement than fathers, while
      gender differences in critical comments were nonsignificant. The correlation of
      the two subscales of the FQ with a conceptually related measure (Expressed
      Emotion) and two unrelated ones (negative caregiving experience, distress)
      supports the convergent and concurrent validity of the instrument in both
      samples. CONCLUSIONS: The FQ has adequate psychometric properties and may be of
      value in assessing the impact of ED symptoms on the family environment. Finally,
      interventions that aim to reduce Expressed Emotion in carers may consider a
      gender-specific approach.

PMID- 25069551
TI  - Impact of family language and testing language on reading performance in a
      bilingual educational context.
AB  - BACKGROUND: When different languages co-exist in one area, or when one person
      speaks more than one language, the impact of language on psychological and
      educational assessment processes can be considerable. The aim of this work was to
      study the impact of testing language in a community with two official languages:
      Spanish and Basque. METHOD: By taking the PISA 2009 Reading Comprehension Test as
      a basis for analysis, four linguistic groups were defined according to the
      language spoken at home and the test language. Psychometric equivalence between
      test forms and differences in results among the four language groups were
      analyzed. The comparison of competence means took into account the effects of the
      index of socioeconomic and cultural status (ISEC) and gender. RESULTS: One
      reading unit with differential item functioning was detected. The reading
      competence means were considerably higher in the monolingual Spanish-Spanish
      group. No differences were found between the language groups based on family
      language when the test was conducted in Basque. CONCLUSIONS: The study
      illustrates the importance of taking into account psychometric, linguistic and
      sociolinguistic factors in linguistically diverse assessment contexts.

PMID- 25069552
TI  - Prediction of human adaptation and performance in underwater environments.
AB  - BACKGROUND: Environmental stressors require the professional diver to undergo a
      complex process of psychophysiological adaptation in order to overcome the
      demands of an extreme environment and carry out effective and efficient work
      under water. The influence of cognitive and personality traits in predicting
      underwater performance and adaptation has been a common concern for diving
      psychology, and definitive conclusions have not been reached. METHOD: In this ex
      post facto study, psychological and academic data were analyzed from a large
      sample of personnel participating in scuba diving courses carried out in the
      Spanish Navy Diving Center. In order to verify the relevance of individual
      differences in adaptation to a hostile environment, we evaluated the predictive
      validity of general mental ability and personality traits with regression
      techniques. RESULTS: The data indicated the existence of psychological variables
      that can predict the performance ( R2 = .30, p <.001) and adaptation ( R2(N) =
      .51, p <.001) of divers in underwater environment. CONCLUSIONS: These findings
      support the hypothesis that individual differences are related to the probability
      of successful adaptation and effective performance in professional diving. These
      results also verify that dispositional traits play a decisive role in diving
      training and are significant factors in divers' psychological fitness.

PMID- 25069554
TI  - Usefulness of the Bayley scales of infant and toddler development,third edition,
      in the early diagnosis of language disorder.
AB  - BACKGROUND: Language disorder (LD) is a neurodevelopmental disorder, and early
      diagnosis has an impact on speech therapy practice. The aim of this work is to
      test the usefulness of the Cognitive and Language scales of the Bayley-III in the
      early diagnosis of LD. METHOD: In a longitudinal study, a clinical sample of 187
      children with diagnostic hypothesis of communication disorders at 4.5 years was
      assessed with the Bayley-III before age 3.5 years and subsequently with other
      scales of different psychological and psycholinguistic functions. RESULTS: The
      results indicate that children with LD scored significantly lower than their
      control groups in all subtests and compounds of the Bayley-III. Additionally, low
      scores on the Language composite in the Bayley-III predicted lower scores in the
      Auditory-vocal Channel of the ITPA. A significant correlation was obtained
      between the Cognitive Scale of the Bayley-III and the General Cognitive Scale of
      the MSCA and the Mental Processing Composite of the K-ABC. CONCLUSIONS: We can
      draw the conclusion that the Cognitive and Language scales of the Bayley-III are
      a useful instrument for early diagnosis of LD, and can also discriminate more
      severe forms of LD.

PMID- 25069553
TI  - Prevalence of psychological and physical intimate partner aggression in Madrid
      (Spain): a dyadic analysis.
AB  - BACKGROUND: The goal of the present study is to analyze the prevalence of
      bidirectional psychological and physical aggression in intimate partner
      relationships using the Conflict Tactics Scale (CTS-2), and to determine the
      influence of the variables age and relationship duration. METHOD: The
      participants were 3,578 heterosexual couples from the Region of Madrid. RESULTS:
      Bidirectional aggression was the most frequent pattern in the dyadic types of
      aggression examined; we analyzed the prevalences of mutual psychological (46%)
      and physical aggression (4%), reciprocal psychological (41%) and physical
      aggression (3%), and bidirectional psychological (80%) and physical aggression
      (25%). The variables age and relationship duration were significant predictors of
      bidirectional physical and psychological aggression. Younger couples and couples
      with less than a one-year relationship duration assaulted each other the most.
      CONCLUSIONS: These data provide an objective view of bidirectional aggression in
      Spanish community samples and serve as a reference point for prevention and
      intervention programs and forensic reports.

PMID- 25069555
TI  - Assessment and detection of peer-bullying through analysis of the group context.
AB  - BACKGROUND: The assessment of bullying requires an analysis both of the main
      profiles involved in this phenomenon and of the social context in which it
      occurs. By considering both aspects, this study develops a scale that, in
      addition to individual information, incorporates a representation of the group
      structure of the classroom. METHOD: A large sample composed of 11,561 students
      (mean age = 11.12 years, girls = 49.2%) from 108 schools completed the
      Sociescuela Scale by peer reports. An analysis of the internal structure and
      reliability of the scale was performed, as well as of the students' social
      networks. RESULTS: Factor analysis yielded five factors: Victimization,
      Acceptance, Prosociality, Withdrawal, and Aggressiveness. Boys showed more
      victimization and aggressiveness than girls. The results obtained enable us to:
      (a) evaluate a series of individual profiles associated with involvement in
      bullying and their sociometric status, and (b) position them on a social map of
      each classroom. CONCLUSIONS: The data suggested that the scale is reliable and
      valid for use in the detection of bullying and its applied nature facilitates the
      design of school interventions.

PMID- 25069556
TI  - Validity of the DSM-Oriented scales of the Child Behavior Checklist and Youth
      Self-Report.
AB  - BACKGROUND: The school-age versions of the ASEBA (Achenbach System of Empirically
      Based Assessment) incorporate the DSM-Oriented scales. These scales make it
      possible to quantify and normalize problems defined in the DSM. The objective was
      to study the incremental validity of the DSM-Oriented scales of the ASEBA
      inventories, the Child Behavior Checklist - CBCL, completed by parents of
      children aged 6-18 years, and the Youth Self-Report -YSR, a self-report for
      children/adolescents aged 11-18, over: (a) scores on the Syndromes Scales for
      making DSM-IV diagnoses; and (b) diagnoses obtained with structured interviews
      for the assessment of functioning. METHOD: A clinical sample of 420 children and
      adolescents (8-17 years) was assessed with the CBCL, and 108 adolescents were
      assessed with the CBCL and YSR questionnaires. All underwent a diagnostic
      interview, and interviewers completed a measure of global functional impairment.
      RESULTS: The DSM-Oriented scales showed significant incremental validity in
      conjunction with the Empirical Syndrome scales for discriminating DSM-IV
      diagnoses, and considerable incremental validity in conjunction with the
      diagnoses obtained through the diagnostic interview for predicting the level of
      functional impairment. CONCLUSION: DSM-Oriented scales should be considered
      simultaneously with the Syndrome Scales of the ASEBA taxonomy, as they provide
      useful additional information in the clinical process.

PMID- 25069557
TI  - Application of cognitive diagnosis models to competency-based situational
      judgment tests.
AB  - BACKGROUND: Profiling of jobs in terms of competency requirements has
      increasingly been applied in many organizational settings. Testing these
      competencies through situational judgment tests (SJTs) leads to validity problems
      because it is not usually clear which constructs SJTs measure. The primary
      purpose of this paper is to evaluate whether the application of cognitive
      diagnosis models (CDM) to competency-based SJTs can ascertain the underlying
      competencies measured by the items, and whether these competencies can be
      estimated precisely. METHOD: The generalized deterministic inputs, noisy "and"
      gate (G-DINA) model was applied to 26 situational judgment items measuring
      professional competencies based on the great eight model. These items were
      applied to 485 employees of a Spanish financial company. The fit of the model to
      the data and the convergent validity between the estimated competencies and
      personality dimensions were examined. RESULTS: The G-DINA showed a good fit to
      the data and the estimated competency factors, adapting and coping and
      interacting and presenting were positively related to emotional stability and
      extraversion, respectively. CONCLUSIONS: This work indicates that CDM can be a
      useful tool when measuring professional competencies through SJTs. CDM can
      clarify the competencies being measured and provide precise estimates of these
      competencies.

PMID- 25069558
TI  - Improving basic math skills through integrated dynamic representation strategies.
AB  - BACKGROUND: In this paper, we analyze the effectiveness of the Integrated Dynamic
      Representation strategy (IDR) to develop basic math skills. METHOD: The study
      involved 72 students, aged between 6 and 8 years. We compared the development of
      informal basic skills (numbers, comparison, informal calculation, and informal
      concepts) and formal (conventionalisms, number facts, formal calculus, and formal
      concepts) in an experimental group (n = 35) where we applied the IDR strategy and
      in a Control group (n = 37) in order to identify the impact of the procedure.
      RESULTS: The experimental group improved significantly in all variables except
      for number facts and formal calculus. CONCLUSIONS: It can therefore be concluded
      that IDR favors the development of the skills more closely related to applied
      mathematics than those related to automatic mathematics and mental arithmetic.

PMID- 25069559
TI  - The effects of question-generation training on metacognitive knowledge, self
      regulation and learning approaches in science.
AB  - BACKGROUND: Although much research has examined the impact of question generation
      on students' reading comprehension and learning from lectures, far less research
      has analysed its influence on how students learn and study science. The present
      study aims to bridge this knowledge gap. METHOD: Using a quasi-experimental
      design, three complete ninth-grade science classes, with a total of 72 students,
      were randomly assigned to three conditions (groups): (G1) questioning-training by
      providing prompts; (G2) question-generation without any explicit instruction; and
      (G3) no question control. Participants' pre-test and post-test self-reported
      measures of metacognitive knowledge, self-regulation and learning approaches were
      collected and data analysed with multivariate and univariate analyses of
      covariance. RESULTS: (a) MANCOVA revealed a significant effect for group; (b)
      ANCOVAs showed the highest average gains for G1 and statistically significant
      between-group differences in the two components of metacognition: metacognitive
      knowledge and self-regulation; and (c) the direction of these differences seemed
      to vary in each of these components. CONCLUSIONS: Question-generation training
      influenced how students learned and studied, specifically their metacognition,
      and it had a medium to large effect size, which was somewhat related to the
      prompts used.

PMID- 25069560
TI  - Sample size planning for multiple correlation: reply to Shieh (2013).
AB  - BACKGROUND: Bonett and Wright (2011) proposed a simple and accurate sample size
      planning formula for estimating a squared multiple correlation with desired
      relative precision. Shieh (2013) incorrectly evaluated the accuracy of the Bonett
      Wright formula. METHOD: To address a criticism of Shieh that the Bonett-Wright
      formula was not examined under a wider range of conditions, the accuracy of the
      Bonett-Wright sample size formula is evaluated under the additional conditions
      proposed by Shieh. A simple 2-step sample size formula for desired absolute
      precision is proposed and its accuracy is evaluated under the conditions proposed
      by Shieh. RESULTS: The analyses indicate that the Bonett-Wright sample size
      formula for relative prediction and the new 2-step sample size formula for
      absolute precision are remarkably accurate. CONCLUSIONS: Simple sample size
      planning formulas for a squared multiple correlation are important tools in
      designing a multiple regression analysis where the primary goal is to obtain an
      acceptably accurate estimate of the squared multiple correlation. The
      computationally intensive and simulation-based methods proposed by Shieh are not
      necessary.

PMID- 25069561
TI  - Exploratory factor analysis in validation studies: uses and recommendations.
AB  - BACKGROUND: The Exploratory Factor Analysis (EFA) procedure is one of the most
      commonly used in social and behavioral sciences. However, it is also one of the
      most criticized due to the poor management researchers usually display. The main
      goal is to examine the relationship between practices usually considered more
      appropriate and actual decisions made by researchers. METHOD: The use of
      exploratory factor analysis is examined in 117 papers published between 2011 and
      2012 in 3 Spanish psychological journals with the highest impact within the
      previous five years. RESULTS: RESULTS show significant rates of questionable
      decisions in conducting EFA, based on unjustified or mistaken decisions regarding
      the method of extraction, retention, and rotation of factors. CONCLUSIONS:
      Overall, the current review provides support for some improvement guidelines
      regarding how to apply and report an EFA.

PMID- 25069562
TI  - Factor structure and measurement invariance of the Difficulties Emotion
      Regulation Scale (DERS) in Spanish adolescents.
AB  - BACKGROUND: Emotion dysregulation is a unifying dimension of several
      psychopathological symptoms such as prolonged dysphoria, labile mood, high anger,
      persistent fear and excessive worry. Deficits in emotion regulation (ER), or
      emotion dysregulation, appear to be relevant to the development, maintenance, and
      promising treatment target in a broad range of mental disorders. The Difficulties
      in Emotion Regulation Scale (DERS) is the most comprehensive measure of emotion
      dysregulation to date, but the Spanish version has not been validated in
      adolescents. METHOD: A community sample of 642 Spanish adolescents aged 12-18
      responded to the DERS. RESULTS: Factor analysis suggested a six-factor solution,
      and strict measurement invariance across sex was achieved. Internal consistency
      for the subscales was moderate to satisfactory (.71-.88), except for Awareness
      (&alpha; = .62). We found some sex differences on subscale scores, with small
      effect sizes. CONCLUSIONS: The results obtained for the Spanish version of the
      DERS are promising for investigating emotion dysregulation in Spanish
      adolescents.

PMID- 25069563
TI  - Psychometric properties of the Spanish version of the Controlling Coach Behaviors
      Scale in the sport context.
AB  - BACKGROUND: The purpose of this research was to translate into Spanish and
      examine the psychometric properties of the Spanish version of the Controlling
      Coach Behaviors Scale (CCBS) in male soccer players. The CCBS is a questionnaire
      designed to assess athletes' perceptions of sports coaches' controlling
      interpersonal style from the perspective of the self-determination theory.
      METHOD: Study 1 tested the factorial structure of the translated scale using
      confirmatory factor analysis (CFA) and provided evidence of discriminant
      validity. Studies 2 and 3 examined the invariance across time and across
      competitive level via multi-sample CFA. Reliability analyses were also conducted.
      RESULTS: The CFA results revealed that a four-factor model was acceptable,
      indicating that a controlling interpersonal style is a multidimensional construct
      represented by four separate and related controlling coaching strategies.
      Further, results supported the invariance of the CCBS factor structure across
      time and competitive level and provided support for the internal consistency of
      the scale. CONCLUSIONS: Overall, the CCBS demonstrated adequate internal
      consistency, as well as good factorial validity. The Spanish version of the CCBS
      represents a valid and reliable adaptation of the instrument, which can be
      confidently used to measure soccer players' perceptions of their coaches'
      controlling interpersonal style.

PMID- 25069564
TI  - Psychometric properties of the Spanish version of the Experiencing of Self Scale
      (EOSS) for assessment in Functional Analytic Psychotherapy.
AB  - BACKGROUND: The Experiencing of Self Scale (EOSS) was created to evaluate the
      experience of the personal self, within the field of Functional Analytic
      Psychotherapy. This paper presents a study of the reliability and validity of the
      EOSS in a Spanish sample. METHOD: The study sample, chosen from 24 different
      centres, comprised 1,040 participants aged between 18-75, of whom 32% were men
      and 68% women. The clinical sample was made up of 32.7%, whereas 67.3% had no
      known problem. To obtain evidence of convergent validity, other questionnaires
      related to the self (EPQ-R, DES, RSES) were used for comparison. RESULTS: The
      EOSS showed high internal consistency (Cronbach's &alpha; = .941) and
      significantly high correlations with the EPQ-R Neuroticism scale and the DES
      Dissociation scale, while showing negative correlations with the Rosenberg Self
      Esteem Scale (RSES). The EOSS revealed 4 principal factors: a self in close
      relationships, a self with casual social relationships, a self in general and a
      positive self-concept. Significant statistical differences were found between the
      clinical and standard sample, the former showing a higher average. CONCLUSIONS:
      The EOSS had high internal consistency, showing evidence of convergent validity
      with similar scales and proving useful for the assessment of people with
      psychological problems related to the self.

PMID- 25069565
TI  - Psychometric properties of the Spanish Adaptation of the School Attitude
      Assessment Survey-Revised.
AB  - BACKGROUND: The assessment of attitudes toward school with the objective of
      identifying adolescents who may be at risk of underachievement has become an
      important area of research in educational psychology, although few specific tools
      for their evaluation have been designed to date. One of the instruments available
      is the School Attitude Assessment Survey-Revised (SAAS-R). METHOD: The objective
      of the current research is to test the construct validity and to analyze the
      psychometric properties of the Spanish version of the SAAS-R. Data were collected
      from 1,398 students attending different high schools. Students completed the SAAS
      R along with measures of the g factor, and academic achievement was obtained from
      school records. RESULTS: Confirmatory factor analysis, multivariate analysis of
      variance and analysis of variance tests supported the validity evidence.
      CONCLUSIONS: The results indicate that the Spanish version of the SAAS-R is a
      useful measure that contributes to identification of underachieving students.
      Lastly, the results obtained and their implications for education are discussed.

PMID- 25069566
TI  - MRI-guided 3D conformal arc micro-irradiation of a F98 glioblastoma rat model
      using the Small Animal Radiation Research Platform (SARRP).
AB  - Current glioblastoma (GB) small animal models for cranial radiation therapy (RT)
      use simple single beam technologies, which differ from the advanced conformal
      image-guided radiation techniques used in clinical practice. This technological
      disparity presents a major disadvantage for the development of new therapeutic
      approaches. Hence, we established a F98 GB rat model using magnetic resonance
      imaging (MRI)-guided three-dimensional (3D)-conformal arc RT with the Small
      Animal Radiation Research Platform (SARRP). Ten Fischer rats were inoculated with
      F98 tumor cells. When the tumor reached a volume of approximately 27 mm(3) on T2
      weighted MR images, the animals were randomized into a treatment group (n = 5)
      receiving RT and concomitant temozolomide, and a sham group (n = 5) receiving
      control injections. For the treated animals, contrast-enhanced T1-weighted MR
      images were acquired followed by a cone-beam computed tomography (CBCT) on the
      SARRP system. Both scans were co-registered; MRI was used to define the target
      whereas CBCT was used for calculating a dose plan (20 Gy, three non-coplanar arc
      beams, 3 * 3 mm collimator). Tumor volumes were evaluated on follow-up contrast
      enhanced T1-weighted MR images. Verification of treatment accuracy with gammaH2AX
      immunohistochemical staining was performed. Tumors in the control animals showed
      rapid proliferation during follow-up, encompassing almost the entire right
      cerebral hemisphere at day 12-15. Treated animals showed no significant tumor
      growth from 2 to 9 days post RT. gammaH2AX results confirmed the accuracy of dose
      delivery. This model, which is quite similar to the approach in the clinic, is
      valid for combined RT and chemotherapy of GB in rats.

PMID- 25069567
TI  - Prevention of oxidative stress, inflammation and mitochondrial dysfunction in the
      intestine by different cranberry phenolic fractions.
AB  - Cranberry fruit has been reported to have high antioxidant effectiveness that is
      potentially linked to its richness in diversified polyphenolic content. The aim
      of the present study was to determine the role of cranberry polyphenolic
      fractions in oxidative stress (OxS), inflammation and mitochondrial functions
      using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance
      LC(r)-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the
      profile of low, medium and high molecular mass polyphenolic compounds in
      cranberry extracts. The medium molecular mass fraction was enriched with
      flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the
      dominant class of polyphenols in the high molecular mass fraction. Pre-incubation
      of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate
      mediated lipid peroxidation and counteracted lipopolysaccharide-mediated
      inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF
      alpha and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry
      polyphenols (CP) fractions limited both nuclear factor kappaB activation and Nrf2
      down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent
      mitochondrial dysfunctions as shown by the rise in ATP production and the up
      regulation of Bcl-2, as well as the decline of protein expression of cytochrome c
      and apoptotic-inducing factor. These mitochondrial effects were associated with a
      significant stimulation of peroxisome-proliferator-activated receptor gamma co
      activator-1-alpha, a central inducing factor of mitochondrial biogenesis and
      transcriptional co-activator of numerous downstream mediators. Finally, cranberry
      procyanidins forestalled the effect of iron/ascorbate on the protein expression
      of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings
      provide evidence for the capacity of CP to reduce intestinal OxS and inflammation
      while improving mitochondrial dysfunction. 

PMID- 25069568
TI  - Atherosclerosis and tumor suppressor molecules (review).
AB  - Atherosclerosis, the major cause of heart attack and stroke, is a chronic
      inflammatory disease characterized by the formation of atherosclerotic plaque.
      Oxidized low-density lipoprotein through increased oxidative stress has been
      identified as one of the primary factors responsible for atherogenesis. Cell
      proliferation and death are key processes in the progression of atherosclerosis.
      The oxidative environment in areas of lipid accumulation is mainly created by the
      production of reactive oxygen species, which are assumed to mediate vascular
      tissue injury. Oxidative DNA damage and levels of DNA repair are reduced during
      dietary lipid lowering. The tumor suppressor molecules play a pivotal role in
      regulating cell proliferation, DNA repair and cell death, which are important
      processes in regulating the composition of atherosclerotic plaque. Accordingly,
      in this review, we discuss the fundamental role of tumor suppressor molecules in
      regulating atherogenesis. In particular, we discuss how tumor suppressor
      molecules are activated in the complex environment of atherosclerotic plaque, and
      regulate growth arrest, cell senescence and the apoptosis of vascular smooth
      muscle cells, which may protect against the progression of atherosclerosis. In
      addition, we discuss promising alternatives to the use of medications (such as
      statin) against atherosclerosis, namely diet, with the use of plant-derived
      supplements to modulate the expression and/or activity of tumor suppressor
      molecules. We also summarize the progress of research made on herbs with a focus
      on the modulatory roles of tumor suppressors, and on the molecular mechanisms
      underlying the prevention if atherosclerosis, supporting designs for further
      research in this field. 

PMID- 25069569
TI  - Three different cruciate-sacrificing TKA designs: minor intraoperative kinematic
      differences and negligible clinical differences.
AB  - PURPOSE: The goal of this study was to compare three types of mobile-bearing
      posterior cruciate ligament (PCL)-sacrificing TKA. The hypothesis was that the
      three designs provide differences in flexion stability and femoral rollback and
      improved clinical score at 2-year follow-up. METHODS: Three groups of patients,
      divided according to implant design, were analysed retrospectively. All
      operations were guided by a non-image-based navigation system that recorded
      relative femoral and tibial positions in native and implanted knees during:
      passive range of motion and anterior drawer test at 90 degrees  flexion. WOMAC,
      KSS and SF36 scores were collected pre-operatively and at 2-year follow-up.
      RESULTS: There are no differences in kinematic or clinical performance of the
      three implants, except for the antero-posterior translation during stress test in
      flexion: only Cohort B had comparable pre- and post-operative laxity test values
      (p < 0.001). All three TKA designs allowed to maintain pre-operative tibial
      rotation pattern through all range of knee flexion. All clinical scores of the
      three patient cohorts were significantly improved post-operatively compared to
      the pre-operative values (p < 0.001). Moreover, we found no differences among
      post-operative results of the three designs. CONCLUSION: Despite design
      variations, mobile-bearing PCL-sacrificing TKA reproduces femoral rollback and
      screw-home with little or no difference in clinical or functional scores at a
      follow-up of 2 years. LEVEL OF EVIDENCE: III.

PMID- 25069570
TI  - Partial meniscus substitution with a polyurethane scaffold does not improve
      outcome after an open-wedge high tibial osteotomy.
AB  - PURPOSE: The aim of the study was to determine whether medial meniscal
      substitution with a polyurethane scaffold (Actifit((r))) improves the outcome of
      medial meniscal-deficient varus knees undergoing open-wedge high tibial
      osteotomy. METHODS: Sixty patients with symptomatic varus knees those who
      underwent open-wedge high tibial osteotomies were prospectively studied. In 30
      patients, the medial meniscus was left with a defect larger than 25 mm (Group M).
      An Actifit((r)) device was implanted (Group A) in the remaining 30 patients.
      Patients were functionally evaluated with WOMET, IKDC and VAS. Patient
      satisfaction was graded from 0 (not satisfied) to 4 (very satisfied). RESULTS:
      Both groups were comparable preoperatively. They had similar follow-up periods
      (31.2 months; range 24-47.5; n.s.). WOMET improved a mean of 53.4 +/- 8.4 and
      42.4 +/- 17.2 points in Groups M and A, respectively (p = 0.002). IKDC improved a
      mean of 56.7 +/- 12 and 50.3 +/- 15.6 points in Groups M and A, respectively
      (n.s.). VAS dropped 5.9 +/- 2.1 and 4.7 +/- 2.8 points in Groups M and A,
      respectively (p = 0.006). Patient satisfaction averaged 3.3 +/- 0.8 and 3.3 +/- 1
      in Groups M and A, respectively (n.s.). CONCLUSIONS: Patients with symptomatic
      varus knees were treated with open-wedge high tibial osteotomies, and a
      meniscectomy was improved more at short-term follow-up in most of the evaluated
      functional scores than those patients with concomitant implantation of a medial
      Actifit((r)) implant. However, there was no difference in terms of patient
      satisfaction with the procedure. Based on the short-term functional results of
      this study, no data were provided to support medial meniscal substitution with a
      polyurethane scaffold when an open-wedge high tibial osteotomy is being
      performed. LEVEL OF EVIDENCE: Prospective comparative study, Level II.

PMID- 25069571
TI  - High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What
      We Need to Know.
AB  - Neuropathic pain is a frequent and disabling condition with diverse underlying
      etiologies and is often difficult to treat. Systemic drug treatment is often
      limited in efficacy. Furthermore, adverse effects may be a limiting factor when
      trying to reach the necessary dose. Analgesics that can be applied topically have
      the potential to largely overcome this problem. They may be of particular
      advantage in localized neuropathic pain syndromes such as postherpetic neuralgia
      or small fiber neuropathy. Capsaicin, the pungent component of chili peppers, is
      a natural ligand of the transient receptor potential vanilloid 1 channel and has
      long been used as topically applicable cream with concentrations of 0.025 to
      0.075%. In 2009, a high-concentration transdermal capsaicin 8% patch
      (Qutenza((r)); Acorda Therapeutics, Inc., Ardsley, NY, USA; Astellas Pharma
      Europe Ltd., Chertsey, Surrey, UK) was introduced for the treatment of peripheral
      neuropathic pain syndromes other than of diabetic origin in adults. It has since
      been widely used in diverse neuropathic pain disorders. In this review article,
      we summarize current knowledge on Qutenza, its advantages and problems, and
      expose unmet needs. 

PMID- 25069572
TI  - Role of the PNPLA3 I148M polymorphism in nonalcoholic fatty liver disease and
      fibrosis in Korea.
AB  - BACKGROUND: The role of the patatin-like phospholipase domain-containing 3
      (PNPLA3) single-nucleotide polymorphism (SNP), rs738409, in the development and
      progression of nonalcoholic fatty liver disease (NAFLD) has not been studied in
      the Korean population. AIMS: The aim of the study was to investigate the genotype
      frequency and allele distribution of PNPLA3 rs738409 and the association between
      the SNP and development of NAFLD and liver fibrosis. METHODS: A total of 339
      Korean adults (155 NAFLD patients and 184 healthy controls) were enrolled. PNPLA3
      SNP genotyping was carried out using a TaqMan allelic discrimination assay. Liver
      fibrosis severity was evaluated by NAFLD fibrosis score (NFS) and BARD score.
      RESULTS: The frequencies of the PNPLA3 rs738409 genotypes, CC, CG, and GG in the
      healthy control group were 29.9, 50.0, and 20.1%, respectively, and those in
      NAFLD patients were 20.0, 48.4, and 31.6%, respectively, showing a higher
      frequency of the risk allele (G allele) (p = 0.006). Among the NAFLD patients,
      the CG+GG genotype frequency was significantly higher in patients with advanced
      fibrosis, defined as NFS >= -1.455 or BARD score >=2, than in patients with mild
      to-moderate fibrosis (p = 0.012 and p = 0.046, respectively). In multivariate
      analysis, the CG+GG genotype was an independent factor for NAFLD development
      (odds ratio 2.568, 95% CI 1.109-5.945, p = 0.028) and for advanced liver fibrosis
      according to the criteria of NFS >= -1.455 (odds ratio 18.573, 95% CI 2.035
      169.526, p = 0.010) or a BARD score >=2 (odds ratio 4.040, 95% CI 1.084-15.048, p
      = 0.037). CONCLUSION: The PNPLA3 rs738409 polymorphism is common and may confer a
      significant risk of NAFLD and advanced liver fibrosis in the Korean population.

PMID- 25069573
TI  - Transcriptional profiling of peripheral blood in pancreatic adenocarcinoma
      patients identifies diagnostic biomarkers.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy
      associated with poor survival rates. Fast detection of PDAC appears to be the
      most relevant strategy to improve the long-term survival of patients. AIMS: Our
      objective was to identify new markers in peripheral blood that differentiates
      between PDAC patients and healthy controls. METHODS: Peripheral blood samples
      from PDAC patients (n = 18) and controls (n = 18) were analyzed by whole genome
      cDNA microarray hybridization. The most relevant genes were validated by
      quantitative real-time PCR (RT-qPCR) in the same set of samples. Finally, our
      gene prediction set was tested in a blinded set of new peripheral blood samples
      (n = 30). RESULTS: Microarray studies identified 87 genes differentially
      expressed in peripheral blood samples from PDAC patients. Four of these genes
      were selected for analysis by RT-qPCR, which confirmed the previously observed
      changes. In our blinded validation study, the combination of CLEC4D and IRAK3
      predicted the diagnosis of PDAC with 93 % accuracy, with a sensitivity of 86 %
      and specificity of 100 %. CONCLUSIONS: Peripheral blood gene expression profiling
      is an useful tool for the diagnosis of PDAC. We present a validated four-gene
      predictor set (ANKRD22, CLEC4D, VNN1, and IRAK3) that may be useful in PDAC
      diagnosis.

PMID- 25069575
TI  - Combined effects of lead and acid rain on photosynthesis in soybean seedlings.
AB  - To explore how lead (Pb) and acid rain simultaneously affect plants, the combined
      effects of Pb and acid rain on the chlorophyll content, chlorophyll fluorescence
      reaction, Hill reaction rate, and Mg(2+)-ATPase activity in soybean seedlings
      were investigated. The results indicated that, when soybean seedlings were
      treated with Pb or acid rain alone, the chlorophyll content, Hill reaction rate,
      Mg(2+)-ATPase activity, and maximal photochemical efficiency (F(v)/F(m)) were
      decreased, while the initial fluorescence (F 0) and maximum quantum yield (Y)
      were increased, compared with those of the control. The combined treatment with
      Pb and acid rain decreased the chlorophyll content, Hill reaction rate, Mg(2+)
      ATPase activity, F(v)/F(m), and Y and increased F 0 in soybean seedlings. Under
      the combined treatment with Pb and acid rain, the two factors showed additive
      effects on the chlorophyll content in soybean seedlings and exhibited
      antagonistic effects on the Hill reaction rate. Under the combined treatment with
      high-concentration Pb and acid rain, the two factors exhibited synergistic
      effects on the Mg(2+)-ATPase activity, F 0, F v/F m, as well as Y. In summary,
      the inhibition of the photosynthetic process is an important physiological basis
      for the simultaneous actions of Pb and acid rain in soybean seedlings.

PMID- 25069574
TI  - Krupple-like factor 5 is required for proper maintenance of adult intestinal
      crypt cellular proliferation.
AB  - BACKGROUND: Krupple-like factor 5 (KLF5) is a transcription factor that is highly
      expressed in the proliferative compartment of the intestinal crypt. There, it is
      thought to regulate epithelial turnover and homeostasis. AIM: In this study, we
      sought to determine the role for Klf5 in the maintenance of cellular
      proliferation, cytodifferentiation, and morphology of the crypt-villus axis.
      METHODS: Tamoxifen-induced recombination directed by the epithelial-specific
      Villin promoter (in Villin-CreERT2 transgenic mice) was used to delete Klf5 (in
      Klf5 (loxP/loxP) mice) from the adult mouse intestine and analyzed by
      immunostaining and RT-qPCR. Control mice were tamoxifen-treated Klf5 (loxP/loxP)
      mice lacking Villin-CreERT2. RESULTS: Three days after tamoxifen-induced
      recombination, the mitosis marker phospho-histone H3 was significantly reduced
      within the Klf5-mutant crypt epithelium, coincident with increased expression of
      the apoptosis marker cleaved-caspase 3 within the crypt where cell death rarely
      occurs normally. We also observed a reduction in Chromagranin A expressing
      enteroendocrine cells, though no significant change was seen in other secretory
      or absorptive cell types. To examine the long-term repercussions of Klf5 loss, we
      killed mice 5, 14, and 28 days post recombination and found reemerging expression
      of KLF5. Furthermore, we observed restoration of cellular proliferation, though
      not to levels seen wildtype intestinal crypts. Reduction of apoptosis to levels
      comparable to the wildtype intestinal crypt was also observed at later time
      points. Analysis of cell cycle machinery indicated no significant perturbation
      upon deletion of Klf5; however, a reduction of stem cell markers Ascl2, Lgr5, and
      Olfm4 was observed at all time points following Klf5 deletion. CONCLUSIONS: These
      results indicate that Klf5 is necessary to maintain adult intestinal crypt
      proliferation and proper cellular differentiation. Rapid replacement of Klf5
      mutant crypts with wildtype cells and reduction of stem cell markers suggests
      further that Klf5 is required for self renewal of intestinal stem cells.

PMID- 25069576
TI  - Top scientists criticise move to axe scientific adviser to European Commission.

PMID- 25069577
TI  - Costs of care for people with dementia just before and after nursing home
      placement: primary data from eight European countries.
AB  - BACKGROUND: Dementia is the most common cause of functional decline among elderly
      people and is associated with high costs of national healthcare in European
      countries. With increasing functional and cognitive decline, it is likely that
      many people suffering from dementia will receive institutional care in their
      lifetime. To delay entry to institutional care, many European countries invest in
      home and community based care services. OBJECTIVES: This study aimed to compare
      costs for people with dementia (PwD) at risk for institutionalization receiving
      professional home care (HC) with cost for PwD recently admitted to institutional
      long-term nursing care (ILTC) in eight European countries. Special emphasis was
      placed on differences in cost patterns across settings and countries, on the main
      predictors of costs and on a comprehensive assessment of costs from a societal
      perspective. METHODS: Interviews using structured questionnaires were conducted
      with 2,014 people with dementia and their primary informal caregivers living at
      home or in an ILTC facility. Costs of care were assessed with the resource
      utilization in dementia instrument. Dementia severity was measured with the
      standardized mini mental state examination. ADL dependence was assessed using the
      Katz index, neuropsychiatric symptoms using the neuropsychiatric inventory (NPI)
      and comorbidities using the Charlson. Descriptive analysis and multivariate
      regression models were used to estimate mean costs in both settings. A log link
      generalized linear model assuming gamma distributed costs was applied to identify
      the most important cost drivers of dementia care. RESULTS: In all countries costs
      for PwD in the HC setting were significantly lower in comparison to ILTC costs.
      On average ILTC costs amounted to 4,491 Euro per month and were 1.8 fold higher
      than HC costs (2,491 Euro). The relation of costs between settings ranged from
      2.4 (Sweden) to 1.4 (UK). Costs in the ILTC setting were dominated by nursing
      home costs (on average 94%). In the HC setting, informal care giving was the most
      important cost contributor (on average 52%). In all countries costs in the HC
      setting increased strongly with disease severity. The most important predictor of
      cost was ADL independence in all countries, except Spain and France where NPI
      severity was the most important cost driver. A standard deviation increase in ADL
      independence translated on average into a cost decrease of about 22%. CONCLUSION:
      Transition into ILTC seems to increase total costs of dementia care from a
      societal perspective. The prevention of long-term care placement might be cost
      reducing for European health systems. However, this conclusion depends on the
      country, on the valuation method for informal caregiving and on the degree of
      impairment.

PMID- 25069579
TI  - Teens' smoking, drinking, and drug taking at decade low in England.

PMID- 25069578
TI  - Alternative treatment of forearm double fractures: new design intramedullary
      nail.
AB  - OBJECTIVE: This study aims to evaluate the results of intramedullary nail
      treatment in surgical treatment of adult displaced radius and ulna diaphyseal
      fractures. PATIENTS AND METHODS: Eighteen patients (36 forearm fractures) who
      underwent intramedullary nail treatment due to radius and ulna fractures were
      retrospectively analyzed. Adult patients with displaced forearm double fractures
      were included in this study. Patients with open physeal lines, pathological
      fractures, Monteggia and Galeazzi fractures, distal radioulnar joint instability,
      bilateral fractures and bone loss were excluded. RESULTS: Thirteen patients were
      male (72.2 %) and five were female (27.8 %). Average age of the patients was
      35.16 (18-63). Twelve patients (66.7 %) suffered right and six patients (33.3 %)
      left forearm fractures. Average follow-up period was 77.7 (55-162) weeks, average
      bleeding amount was 51.11 (15-100) ml, average time to bone union was 11.3 (8-20)
      weeks, average surgery time was 61.94 (45-80) min and average fluoroscopy time
      was approximately 2 (1-5) min. According to Grace-Eversman criteria, results were
      excellent in 14 (77.8 %) patients, good in 3 (16.8 %) and acceptable in 1 (5.6
      %). Average DASH questionnaire score was 15.15 (4-38.8). There was no iatrogenic
      vascular, neural and bone injury during surgery. There was late rupture of
      extensor pollicis longus tendon in one patient, 4 months after surgery.
      CONCLUSION: Intramedullary fixation method has advantages, such as closed
      application, short surgery period, good cosmetic results and early return to
      movement. We think intramedullary fixation method may be used as an alternative
      treatment method to plate osteosynthesis in surgical treatment of radius and ulna
      diaphyseal fractures.

PMID- 25069580
TI  - Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new
      insights.
AB  - Diabetic foot ulcers (DFUs) are one of the most common and serious complications
      of diabetes mellitus, as wound healing is impaired in the diabetic foot. Wound
      healing is a dynamic and complex biological process that can be divided into four
      partly overlapping phases: hemostasis, inflammation, proliferative and
      remodeling. These phases involve a large number of cell types, extracellular
      components, growth factors and cytokines. Diabetes mellitus causes impaired wound
      healing by affecting one or more biological mechanisms of these processes. Most
      often, it is triggered by hyperglycemia, chronic inflammation, micro- and macro
      circulatory dysfunction, hypoxia, autonomic and sensory neuropathy, and impaired
      neuropeptide signaling. Research focused on thoroughly understanding these
      mechanisms would allow for specifically targeted treatment of diabetic foot
      ulcers. The main principles for DFU treatment are wound debridement, pressure off
      loading, revascularization and infection management. New treatment options such
      as bioengineered skin substitutes, extracellular matrix proteins, growth factors,
      and negative pressure wound therapy, have emerged as adjunctive therapies for
      ulcers. Future treatment strategies include stem cell-based therapies, delivery
      of gene encoding growth factors, application of angiotensin receptors analogs and
      neuropeptides like substance P, as well as inhibition of inflammatory cytokines.
      This review provides an outlook of the pathophysiology in diabetic wound healing
      and summarizes the established and adjunctive treatment strategies, as well as
      the future therapeutic options for the treatment of DFUs. 

PMID- 25069581
TI  - Identification of ultraviolet B radiation-induced microRNAs in normal human
      dermal papilla cells.
AB  - Ultraviolet (UV) radiation impairs intracellular functions by directly damaging
      DNA and by indirectly generating reactive oxygen species (ROS), which induce cell
      cycle arrest and apoptosis. UV radiation can also alter gene expression profiles,
      including those of mRNA and microRNA (miRNA). The effects of UV radiation on
      cellular functions and gene expression have been widely documented in human skin
      cells such as keratinocytes, melanocytes and dermal fibroblasts, but the effect
      it has on other types of skin cell such as dermal papilla cells, which are
      crucial in the induction of hair follicle growth, remains unknown. In the current
      study, the effect of UV radiation on physiological changes and miRNA-based
      expression profiles in normal human dermal papilla cells (nHDPs) was
      investigated. UVB radiation of >=50 mJ/cm2 displayed high cytotoxicity and
      apoptosis in a dose-dependent manner. In addition, ROS generation was exhibited
      in UVB-irradiated nHDPs. Furthermore, using miRNA microarray analysis, it was
      demonstrated that the expression profiles of 42 miRNAs in UVB-irradiated nHDPs
      were significantly altered compared with those in the controls (35 upregulated
      and 7 downregulated). The biological functions of the differentially expressed
      miRNAs were studied with gene ontology analysis to identify their putative target
      mRNAs, and were demonstrated to be involved in cell survival- and death-related
      functions. Overall, the results of the present study provide evidence that miRNA
      based cellular mechanisms may be involved in the UVB-induced cellular response in
      nHDPs.

PMID- 25069582
TI  - Effects of land use changes on the ecosystem service values of coastal wetlands.
AB  - Changes in the coastal landscape of Southern Sinaloa (Mexico), between 2000 and
      2010, were analyzed to relate spatial variations in wetlands extent with the
      provision and economic value of the ecosystem services (ES). Remote sensing
      techniques applied to Landsat TM imagery were used to evaluate land use/land
      cover changes while the value transfer method was used to assess the value of ES
      by land cover category. Five wetland types and other four land covers were found
      as representative of the coastal landscape. Findings reveal a 14 % decrease in
      the saltmarsh/forested mangrove area and a 12 % increase in the area of shrimp
      pond aquaculture (artificial wetland) during the study period. ES valuation shows
      that the total value flow increased by 9 % from $215 to $233 million (2007 USD)
      during the 10-year period. This increase is explained as result of the high value
      worldwide assigned to saltmarsh. We recognize limitations in the transfer-based
      approach in quantifying and mapping ES values in the region, but this method
      provides with value estimates spatially defined, and also provides some guidance
      in the preliminary screening of policies and projected development in the context
      of data-scarce regions.

PMID- 25069583
TI  - An advanced algorithm for fetal heart rate estimation from non-invasive low
      electrode density recordings.
AB  - Non-invasive fetal electrocardiography is still an open research issue. The
      recent publication of an annotated dataset on Physionet providing four-channel
      non-invasive abdominal ECG traces promoted an international challenge on the
      topic. Starting from that dataset, an algorithm for the identification of the
      fetal QRS complexes from a reduced number of electrodes and without any a priori
      information about the electrode positioning has been developed, entering into the
      top ten best-performing open-source algorithms presented at the challenge.In this
      paper, an improved version of that algorithm is presented and evaluated
      exploiting the same challenge metrics. It is mainly based on the subtraction of
      the maternal QRS complexes in every lead, obtained by synchronized averaging of
      morphologically similar complexes, the filtering of the maternal P and T waves
      and the enhancement of the fetal QRS through independent component analysis (ICA)
      applied on the processed signals before a final fetal QRS detection stage. The RR
      time series of both the mother and the fetus are analyzed to enhance
      pseudoperiodicity with the aim of correcting wrong annotations. The algorithm has
      been designed and extensively evaluated on the open dataset A (N = 75), and
      finally evaluated on datasets B (N = 100) and C (N = 272) to have the mean scores
      over data not used during the algorithm development. Compared to the results
      achieved by the previous version of the algorithm, the current version would mark
      the 5th and 4th position in the final ranking related to the events 1 and 2,
      reserved to the open-source challenge entries, taking into account both official
      and unofficial entrants. On dataset A, the algorithm achieves 0.982 median
      sensitivity and 0.976 median positive predictivity. 

PMID- 25069584
TI  - Oncogenic role and therapeutic target of transient receptor potential melastatin
      7 channel in malignancy.
AB  - INTRODUCTION: The transient receptor potential (TRP) family is a superfamily of
      cation channels which regulates many features of malignant cancers, such as lack
      of differentiation, increased migratory and invasive phenotype and
      chemoresistance. The TRP cation channel, TRPM7 (subfamily M, member 7), is a
      ubiquitous, Ca2+ and Mg2+-permeant ion channel that is unique in that it is an
      ion channel and a serine/threonine kinase. TRPM7 has been associated with cell
      proliferation, survival and development and thus correlated with growth and
      progression of several types of tumor cells, including breast cancer, gastric
      cancer, head and neck cancer, nasopharyngeal carcinoma, pancreatic cancer,
      prostate cancer, retinoblastoma and leukemia. Increased TRPM7 expression in human
      breast and pancreatic cancer tissues also correlates with clinicopathological
      parameters, such as tumor grade, the Ki-67 proliferation index and patient
      survival. AREAS COVERED: In this review, we focus on recent advancements in
      knowledge of aberrant TRPM7 channel function and its contribution to tumor
      progression and angiogenesis. This includes crosstalk between multiple signaling
      pathways. The role of TRPM7 in tumor development, particularly in regard to its
      channel function mediating both Ca2+ and Mg2+ influx as well as its kinase
      activity is also addressed. In addition, we will discuss its role in the stem
      cell and cancer stem cell, as well as its potential as tumor drug target. EXPERT
      OPINION: Better understanding of the structure, function and regulation of TRPM7
      channel, as well as its complex crosstalk with other oncogenic signals in tumor
      cells will be essential to ensure rational use of treatment and development of
      new combinatory therapeutic possibilities.

PMID- 25069585
TI  - ADHD Among Rural Southeastern Nigerian Primary School Children: Prevalence and
      Psychosocial Factors.
AB  - OBJECTIVE: To determine the prevalence of ADHD among primary school pupils in a
      rural community in Southeastern Nigeria and to determine the psychosocial factors
      associated with the condition. METHOD: One hundred eighty-one randomly selected
      participants had their teachers complete the school version of ADHD Rating Scale
      IV. Their parents also completed a sociodemographic questionnaire, the clinical
      interview form for the child and adolescent ADHD patients, and home version of
      the ADHD Rating Scale-IV. RESULTS: Twelve (6.6%) of the children met the criteria
      for diagnosis. A history of prolonged labor (odds ratio [OR] = 14.1; 95%
      confidence interval [CI] = [2.13, 93.1]), and parents' negative assessment of
      their marriages (OR = 0.1; CI = [0.017, 0.567]) were the most predominant factors
      which independently associated with the ADHD in the children. CONCLUSION: There
      is, therefore, a need for the care of rural dwelling African children, who
      otherwise would have difficulties accessing health care that is concentrated in
      the cities.

PMID- 25069587
TI  - Proposed method for predicting pair matching of skeletal elements allows too many
      false rejections.
AB  - Byrd proposes a method for predicting pair matches in commingled remains to
      reduce visual comparison. The method compares differences between left and right
      postcranial element measurements in commingled samples with differences in known
      pairs from a reference sample using a t-score approach. We duplicated his
      protocol using six elements from two samples of known paired elements (n = 854 to
      1063) and calculated the number of pairs correctly predicted. Time commitment was
      estimated by mathematically attempting matches with all left and right elements
      in these samples. Although the results show an 86% reduction in the number of
      potential pairs requiring visual matching, we do not recommend the method because
      (i) the normality assumption for use of a t-score approach is violated, (ii) no
      account is made for bilateral asymmetry, and (iii) the high rate of false
      rejections (up to 22%) undermines its ability to show true incompatibilities for
      potential pair matches.

PMID- 25069586
TI  - New evidence for gait abnormalities among Parkinson's disease patients who suffer
      from freezing of gait: insights using a body-fixed sensor worn for 3 days.
AB  - Previous studies conducted in laboratory settings suggest that the gait pattern
      in between freezing of gait (FOG) episodes is abnormal among patients with
      Parkinson's disease (PD) who suffer from FOG (i.e., "freezers"), compared to
      those who do not (i.e., "non-freezers"). We evaluated whether long-term
      recordings also reveal gait alterations in freezers and if these features were
      related to freezing severity and its impact on daily function. 72 patients with
      PD wore a 3-D accelerometer for 3 days. Acceleration-derived gait features
      included quantity (e.g., the amount of walking) and quality measures (e.g., gait
      variability). The New FOG-Questionnaire evaluated the subject's perceptions of
      FOG severity and its impact. Age, gender, and disease duration were similar (p >
      0.19) in the 28 freezers and 44 non-freezers. Walking quantity was similar in the
      two groups, while freezers walked with higher gait variability (i.e., larger
      anterior-posterior power spectral density width; p = 0.003) and lower gait
      consistency (i.e., lower vertical stride regularity; p = 0.007). Group
      differences were observed when comparing the typical (i.e., median), best, and
      worst performance among the multiple walking bouts measured. Vertical and medio
      lateral gait consistency were associated with the impact of FOG on daily living
      (r < -0.39, p < 0.044). The present findings demonstrate that freezers have
      altered gait variability and consistency during spontaneous community ambulation,
      even during optimal performance, and that these measures are associated with the
      impact of FOG on daily function. Long-term recordings may provide new insights
      into PD and augment the monitoring of FOG and its response to therapy.

PMID- 25069589
TI  - Atomic layer deposition of a MoS2 film.
AB  - A mono- to multilayer thick MoS2 film has been grown by using the atomic layer
      deposition (ALD) technique at 300  degrees C on a sapphire wafer. ALD provides
      precise control of the MoS2 film thickness due to pulsed introduction of the
      reactants and self-limiting reactions of MoCl5 and H2S. A post-deposition
      annealing of the ALD-deposited monolayer film improves the crystallinity of the
      film, which is evident from the presence of triangle-shaped crystals that exhibit
      strong photoluminescence in the visible range.

PMID- 25069590
TI  - Determination of Aroclor 1260 in soil samples by gas chromatography with mass
      spectrometry and solid-phase microextraction.
AB  - A novel fast screening method was developed for the determination of
      polychlorinated biphenyls that are constituents of the commercial mixture,
      Aroclor 1260, in soil matrices by gas chromatography with mass spectrometry
      combined with solid-phase microextraction. Nonequilibrium headspace solid-phase
      microextraction with a 100 MUm polydimethylsiloxane fiber was used to extract
      polychlorinated biphenyls from 0.5 g of soil matrix. The use of 2 mL of saturated
      potassium dichromate in 6 M sulfuric acid solution improved the reproducibility
      of the extractions and the mass transfer of the polychlorinated biphenyls from
      the soil matrix to the microextraction fiber via the headspace. The extraction
      time was 30 min at 100 degrees C. The percent recoveries, which were evaluated
      using an Aroclor 1260 standard and liquid injection, were within the range of
      54.9-65.7%. Two-way extracted ion chromatogram data were used to construct
      calibration curves. The relative error was <+/-15% and the relative standard
      deviation was <15%, which are respective measures of the accuracy and precision.
      The method was validated with certified soil samples and the predicted
      concentrations for Aroclor 1260 agreed with the certified values. The method was
      demonstrated to be linear from 10 to 1000 ng/g for Aroclor 1260 in dry soil. 

PMID- 25069588
TI  - Identification of host genes that affect acquisition of an integrative and
      conjugative element in Bacillus subtilis.
AB  - Conjugation, a major type of horizontal gene transfer in bacteria, involves
      transfer of DNA from a donor to a recipient using donor-encoded conjugation
      machinery. Using a high-throughput screen (Tn-seq), we identified genes in
      recipients that contribute to acquisition of the integrative and conjugative
      element ICEBs1 by Bacillus subtilis. We found that null mutations in some genes
      caused an increase, and others a decrease in conjugation efficiency. Some
      mutations affected conjugation only when present in recipients. Other mutations
      affected conjugation when present in donors or recipients. Most of the genes
      identified are known or predicted to affect the cell envelope. Several encode
      enzymes involved in phospholipid biosynthesis and one encodes a homologue of
      penicillin-binding proteins. Two of the genes identified also affected
      conjugation of Tn916, indicating that their roles in conjugation may be general.
      We did not identify any genes in recipients that were essential for ICEBs1
      conjugation, indicating that if there are such genes, then these are either
      essential for cell growth or redundant. Our results indicate that acquisition of
      ICEBs1, and perhaps other conjugative elements, is robust and not easily avoided
      by mutation and that several membrane-related functions affect the efficiency of
      conjugation. 

PMID- 25069591
TI  - Application of quality by design (QbD) to formulation and processing of naproxen
      pellets by extrusion-spheronization.
AB  - The aim of this research was to apply quality by design (QbD) to the development
      of naproxen loaded core pellets which can be used as the potential core for colon
      specific pellets. In the early stages of this study, prior knowledge and
      preliminary studies were systematically incorporated into the risk assessment
      using failure mode and effect analysis (FMEA) and fishbone diagram. Then Plackett
      Burman design was used to screen eight potential high risk factors
      (spheronization speed, spheronization time, extrusion speed, drying method, CCMC
      Na concentration, lactose concentration, water concentration and Tween 80
      concentration) obtained from the above risk assessment. It was discovered that
      out of the eight potential high risk factors only three factors (spheronization
      speed, extrusion speed and CCMC-Na concentration) had significant effects on the
      quality of the pellets. This allowed the use of Box-Behnken design (BBD) to fully
      elucidate the relationship between the variables and critical quality attribute
      (CQA). Finally, the final control space was established within which the quality
      of the pellets can meet the requirement of colon-specific drug delivery system.
      This study demonstrated that naproxen loaded core pellets were successfully
      designed using QbD principle.

PMID- 25069593
TI  - Elucidation of intestinal absorption mechanism of carvedilol-loaded solid lipid
      nanoparticles using Caco-2 cell line as an in-vitro model.
AB  - Abstract Enhanced oral bioavailability of poorly aqueous soluble drugs
      encapsulated in solid lipid nanoparticles (SLNs) via lymphatic delivery has been
      documented. Since no in-vitro lymphoid tissue is currently available, human
      excised Caco-2 cell monolayer could be alternative tissue for development of an
      in-vitro model to be used as a screening tool before animal studies are
      undertaken. Therefore, optimized carvedilol-loaded SLNs (FOPT-SLNs) were
      prepared, characterized, and evaluated using Caco-2 cell line as an in-vitro
      model. Physical mixture of components of FOPT-SLNs (FOPT-PM) and carvedilol
      solution were used as control groups. From the studies of effect of SLNs
      concentration and cells incubation time, suitable carvedilol concentration and
      incubation time were selected for the model in which cells were subjected to five
      pretreatments for 24 h or 1 h of cell incubation and then followed with treatment
      of FOPT-SLNs, FOPT-PM or 100 ug/mL solution of carvedilol, for additional 24 h of
      cell incubation. The results obtained in this model suggest that main absorption
      mechanism of FOPT-SLNs could be endocytosis and, more specifically, clathrin
      mediated endocytosis. When Transwell(r) permeable supports were used for the
      cells, carrier-mediated mechanism for FOPT-SLNs and passive absorption mechanism
      (transcellular and paracellular) for FOPT-PM and drug solution were concluded.

PMID- 25069592
TI  - Taste-masked orodispersible tablets of cyclosporine self-nanoemulsion lyophilized
      with dry silica.
AB  - The aim of the current study was to investigate the effects of formulation
      parameters on the disintegration, water absorption and dissolution
      characteristics of cyclosporine A (CyA) loaded self-emulsifying drug delivery
      system (SEDDS) in an orodispersible compacts. Its taste masking efficiency was
      also attempted using an electronic tongue. ODTs were prepared by freeze-drying
      liquid SEDDS and synthetic amorphous silica suspension followed by direct
      compression. The influences of the compression forces and super-disintegrant were
      evaluated to optimize tablet characteristics. The liquid SEDDS was characterized
      by vesicular size of 48.5 nm, polydispersity index of 0.95, turbidity of 40.7 NTU
      and rapid CyA dissolution and emulsification rate. The results of micrometric
      studies demonstrated an acceptable flow, hardness and friability to indicate good
      mechanical strength of ODTs. The interaction and Pareto charts demonstrated a
      greater effect of low compression force to increase the porosity and facilitate
      the disintegration rather than the deformation action of the super-disintegrant.
      Super-disintegrant level was the most important factor affecting the dissolution
      parameter followed by the compression force then their interaction effect.
      Moreover, as indicated by Euclidean distance values and discrimination indices,
      the unpalatable taste and aversion taste of CyA to stimuli were masked in its
      optimized SEDDS incorporated ODTs. 

PMID- 25069594
TI  - Electrical percolation characteristics of metallic single-walled carbon nanotube
      networks by vacancy evolution.
AB  - In the present study, we demonstrate the effect of vacancy evolution on high-pure
      metallic single-walled carbon nanotube (m-SWCNT) networks by observing the
      electrical characteristics of the networks on the field-effect transistor (FET).
      By catalytic oxidation using Co catalyst, vacancy evolution was gradually
      realized in high-pure m-SWCNT formed as networks between source-drain electrodes
      of FET. The evolution of vacancy defects in the m-SWCNT networks gradually
      proceeded by heating FET several times at 250  degrees C in air. Atomic force
      microscopic images showed the presence of the Co catalyst nanoparticles, which
      were evenly formed in the m-SWCNT networks between the electrodes of FET. Vacancy
      evolution was confirmed by monitoring the D- and G-bands in the Raman spectra
      measured from the networks after every step of the catalytic oxidation. With
      vacancy evolution in the networks, the D-band gradually increased, and the
      transconductance of m-SWCNT networks drastically decreased. In addition, the
      metallic behaviour of the m-SWCNT networks was converted into a semiconducting
      one with an on/off ratio of 2.7. 

PMID- 25069595
TI  - How multidrug resistance in typhoid fever affects treatment options.
AB  - Salmonella enterica serotype Typhi (S. Typhi) is an enteric pathogen that causes
      typhoid fever. The infection can be severe, with significant morbidity and
      mortality, requiring antimicrobial therapy. Cases of S. Typhi infection in the
      United States and other developed countries are often associated with travel to
      endemic regions. The empirical use of first-line drugs for therapy, including
      ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, has resulted in
      transmissible multidrug resistance. With the global increase in multidrug
      resistant S. Typhi, use of ciprofloxacin, with excellent oral absorption, few
      side effects, and cost-effectiveness, has become popular for treatment. However,
      decreased ciprofloxacin susceptibility due to point mutations in the S. Typhi
      genes gyrA and/or parC has caused treatment failures, necessitating alternative
      therapeutic options. S. Typhi is typically genetically homogenous, with
      phylogenetic and epidemiological studies showing that identical clones and
      diverse S. Typhi types often coexist in the same geographic region. Studies
      investigating point mutations have demonstrated that selective pressure from
      empirical use of first-line drugs and fluoroquinolones has led to the global
      emergence of haplotype H-58. Antibiotic resistance is subject to high selective
      pressure in S. Typhi and thus demands careful use of antimicrobials. 

PMID- 25069596
TI  - Polymorphism in 2-X-adamantane derivatives (X = Cl, Br).
AB  - The polymorphism of two 2-X-adamantane derivatives, X = Cl, X = Br, has been
      studied by X-ray powder diffraction and normal- and high-pressure (up to 300 MPa)
      differential scanning calorimetry. 2-Br-adamantane displays a low-temperature
      orthorhombic phase (space group P212121, Z = 4) and a high-temperature plastic
      phase (Fm3m, Z = 4) from 277.9 +/- 1.0 K to the melting point at 413.4 +/- 1.0 K.
      2-Cl-adamantane presents a richer polymorphic behavior through the temperature
      range studied. At low temperature it displays a triclinic phase (P1, Z = 2),
      which transforms to a monoclinic phase (C2/c, Z = 8) at 224.4 +/- 1.0 K, both
      phases being ordered. Two high-temperature orientationally disordered are found
      for this compound, one hexagonal (P63/mcm, Z = 6) at ca. 241 K and the highest
      one, cubic (Fm3m, Z = 4), being stable from 244 +/- 1.0 K up to the melting point
      at 467.5 +/- 1.0 K. No additional phase appears due to the increase in pressure
      within the studied range. The intermolecular interactions are found to be weak,
      especially for the 2-Br-adamantane compound for which the Br...Br as well as C
      Br...H distances are larger than the addition of the van der Waals radii, thus
      confirming the availability of this compound for building up diamondoid blocks. 

PMID- 25069597
TI  - A novel perovskite based catalyst with high selectivity and activity for partial
      oxidation of methane for fuel cell applications.
AB  - Solid oxide fuel cells (SOFCs) have the potential to revolutionise the present
      fuel economy due to their higher fuel conversion efficiency compared with
      standard heat engines and the possibility of utilizing the heat produced in a
      combined heat and power system. One of the reasons they have yet to fulfil this
      potential is that the conventional anode material of choice, a nickel/yttria
      stabilised zirconia cermet, requires a high temperature production process and
      under operating conditions is susceptible to carbon and sulphur poisoning.
      Perovskite-based materials have been proposed as potential anode materials for
      SOFCs due to their potentially high electronic conductivity and catalytic
      properties. One of the problems in realizing this potential has been their low
      catalytic activity towards methane reforming compared to conventional nickel
      based cermet materials. A nickel doped strontium zirconate material produced by
      low temperature hydrothermal synthesis is described which has high activity for
      methane reforming and high selectivity towards partial oxidation of methane as
      opposed to total oxidation products. Initial studies show a very low level of
      carbon formation which does not increase over time. 

PMID- 25069598
TI  - Association between an educational intervention and a reduction in inappropriate
      troponin testing in patients presenting to an adult emergency department.
AB  - BACKGROUND: High-sensitivity troponin replaced the fourth generation assay at our
      institution in July 2010. Prior experience suggested that the number of positive
      tests with the new assay may double, and that many troponin requests were
      inappropriate. AIM: Primarily, this study aims to design and measure the effect
      of an educational intervention to reduce the number of inappropriate troponin
      tests. Second, other objectives are to compare weekly totals of troponin tests
      before and after the intervention, to note patients with missed acute coronary
      syndrome (ACS) during the study period and to survey clinicians regarding their
      likely troponin ordering practices in certain clinical scenarios. METHODS: A
      staff survey informed the content of the educational intervention. Criteria for
      inappropriate testing were defined prior to the study. Retrospective notes review
      of pre-and post-intervention cohorts were used to determine the reduction in
      inappropriate troponin tests. RESULTS: Ninety-six patients were in each cohort.
      The proportion of inappropriate tests fell from 43% (95% confidence interval (CI)
      33-53) pre-intervention to 22% (95% CI 14-31) post-intervention, P = 0.002.
      Weekly total of troponin tests performed decreased from a mean of 298 (95% CI,
      290-307) pre-intervention to 244 (95% CI 232-255) post-intervention, P < 0.001.
      No cases of missed ACS were found; all cause mortality was unchanged following
      the intervention. CONCLUSION: Our educational intervention was associated with a
      reduction in inappropriate use of troponin tests and a reduction in the total
      number of tests requested, with no known missed ACS. Others faced with a change
      to a high-sensitivity assay should consider a similar intervention.

PMID- 25069599
TI  - Global distribution and prevalence of hepatitis C virus genotypes.
AB  - Hepatitis C virus (HCV) exhibits high genetic diversity, characterized by
      regional variations in genotype prevalence. This poses a challenge to the
      improved development of vaccines and pan-genotypic treatments, which require the
      consideration of global trends in HCV genotype prevalence. Here we provide the
      first comprehensive survey of these trends. To approximate national HCV genotype
      prevalence, studies published between 1989 and 2013 reporting HCV genotypes are
      reviewed and combined with overall HCV prevalence estimates from the Global
      Burden of Disease (GBD) project. We also generate regional and global genotype
      prevalence estimates, inferring data for countries lacking genotype information.
      We include 1,217 studies in our analysis, representing 117 countries and 90% of
      the global population. We calculate that HCV genotype 1 is the most prevalent
      worldwide, comprising 83.4 million cases (46.2% of all HCV cases), approximately
      one-third of which are in East Asia. Genotype 3 is the next most prevalent
      globally (54.3 million, 30.1%); genotypes 2, 4, and 6 are responsible for a total
      22.8% of all cases; genotype 5 comprises the remaining <1%. While genotypes 1 and
      3 dominate in most countries irrespective of economic status, the largest
      proportions of genotypes 4 and 5 are in lower-income countries. CONCLUSION:
      Although genotype 1 is most common worldwide, nongenotype 1 HCV cases-which are
      less well served by advances in vaccine and drug development-still comprise over
      half of all HCV cases. Relative genotype proportions are needed to inform
      healthcare models, which must be geographically tailored to specific countries or
      regions in order to improve access to new treatments. Genotype surveillance data
      are needed from many countries to improve estimates of unmet need.

PMID- 25069600
TI  - p16(INK4a) overexpression is not linked to oncogenic human papillomaviruses in
      patients with high-grade urothelial cancer cells.
AB  - BACKGROUND: p16(INK4a) Is overexpressed in almost all precancerous and
      carcinomatous lesions of the uterine cervix, secondary to interference between
      high-risk human papillomaviruses (hr-HPVs) and the retinoblastoma gene product.
      Overexpression of p16(INK4a) has also been identified in patients with high-grade
      urothelial lesions, both cytologically and histologically. However, the
      etiological role of HPV has not been documented except in inverted papillomas,
      low-grade bladder tumors, and younger patients. We therefore attempted to verify
      if HPV DNA was detectable in p16(INK4a) -positive urothelial tumors. METHODS: A
      total of 90 urinary cytology samples (33 negative/low-grade cases and 57 high
      grade proliferations) were analyzed for p16(INK4a) and HPV DNA. HPV genotyping
      was performed by polymerase chain reaction using a low-density DNA microarray
      enabling the detection of 35 HPVs. A reasoned approach combining tissue
      genotyping and in situ hybridization (ISH) for hr-HPVs was used in patients with
      urinary HPV. RESULTS: Low-risk HPV (HPV-84) and hr-HPVs (HPV-16, -31, and -70)
      were detected. The prevalence of hr-HPVs in the urine was low: 5 of 82 patients
      (6.1%) and only 4 of 50 patients (8.0%) with high-grade urothelial malignancy.
      p16(INK4a) overexpression was noted in 49 high-grade samples (85.9%). In patients
      with p16(INK4a) -positive tumor cells and hr-HPV in the urine, HPV genotyping and
      ISH for hr-HPVs were negative in matched tissue sections. CONCLUSIONS: Our study
      shows a low prevalence of hr-HPVs in the urine of patients with high-grade
      urothelial malignancy. In those, p16(INK4a) overexpression occurs in the absence
      of demonstrable HPV DNA in the tissue sections, contrary to what is noted in
      gynecopathology.

PMID- 25069601
TI  - Dissociation and posttraumatic stress disorder: a latent profile analysis.
AB  - The fifth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM
      5; American Psychiatric Association, ) contains a dissociative subtype for
      posttraumatic stress disorder (PTSD) characterized by significant
      depersonalization and derealization. In this study the PTSD dissociative subtype
      was examined using latent profile analysis in a sample of 541 trauma-exposed
      college students. Items from the PTSD Checklist and Multiscale Dissociation
      Inventory were used as latent class indicators. Results supported a 3-class
      solution including a well-adjusted class, a PTSD class, and a PTSD/dissociative
      class characterized by elevated symptoms of PTSD, depersonalization, and
      derealization. Significant class differences were found on a number of measures
      of related psychopathology with Cohen's d effect size estimates ranging from 0.04
      to 1.86. Diagnostic and treatment implications regarding the dissociative subtype
      are discussed. 

PMID- 25069602
TI  - Intraoperative image-guided transoral robotic surgery: pre-clinical studies.
AB  - BACKGROUND: Adequate resection of oropharyngeal neoplasms with transoral robotic
      surgery (TORS) poses multiple challenges, including difficulty with access,
      inability to palpate the tumor, loss of landmarks, and intraoperative patient
      positioning with mouth retractor and tongue extended creating significant tissue
      distortion from preoperative imaging. METHODS: This study evaluates a workflow
      integrating intraoperative cone beam computed tomography (CBCT) for image-guided
      TORS through robotic experimentation locating 8-10 embedded targets in five
      porcine tongues and a cadaveric head phantom, conducted under various modes of
      visualization and integration of preoperative/intraoperative imaging. RESULTS: A
      statistically significant improvement in mean target localization error was
      achieved for both the porcine tongue ((9.8 +/- 4.0) mm vs. (5.3 +/- 1.3) mm, P
      value = 0.0151) and cadaver ((11.2 +/- 5.0) mm vs. (5.8 +/- 2.5) mm P-value =
      0.0189) in experiments comparing scenarios simulating current standard-of-care
      practice and the proposed image guidance system. CONCLUSION: Intraoperative image
      guidance with augmentation of critical surgical structures has the potential to
      improve target localization for TORS.

PMID- 25069603
TI  - Very low calorie diet without aspartame in obese subjects: improved metabolic
      control after 4 weeks treatment.
AB  - BACKGROUND: Very low calorie diet (VLCD) is routinely used in programs for
      treatment of obesity and before bariatric surgery in order to reduce risk of
      postoperative complications. Aspartame, an artificial sweetener, is commonly used
      in VLCD and is well approved as a food additive without any adverse effects. The
      development of a new fructose containing VLCD formula without aspartame raises
      questions as to effects on glucose and lipid control. METHODS: As part of an
      ongoing study of a novel bariatric surgery procedure, twenty-five obese subjects
      with mean body mass index (BMI) 39.8 kg/m2 and mean age of 48.8 years enrolled in
      a single center observational study. Seven subjects presented with type 2
      diabetes mellitus. The subjects underwent four weeks dietary treatment with VLCD
      Slanka (Slanka). Blood samples including fasting plasma glucose, HbA1c,
      cholesterol and triglycerides were performed at start and after four weeks of
      diet. Blood pressure and weight were noted. RESULTS: All subjects completed the
      diet without any adverse events. Mean weight reduction was 8.2 kg with 95%
      confidence interval 7.1-9.2 kg (p = 0.001). Excess weight (i.e. proportion of
      weight exceeding BMI 25) loss decreased by median 19.5% (inter quartile range
      (IQR) 16,8-24,2). Median fasting plasma glucose was at inclusion 5,6 mmol/l (IQR
      5,3-6,8) and after diet 4.8 mmol/l (IQR 4,6-5,2) (p = 0.001). Median HbA1c
      changed from 39 mmol/mol (IQR 37-44) to 37 mmol/mol (IQR 35-43) (p = 0.001).
      There was also significant reduction in cholesterol and triglyceride levels as
      well as in systolic blood pressure. Changes in other monitored blood chemistry
      values were without clinical importance. CONCLUSION: Four weeks treatment with
      fructose containing VLCD of obese subjects preparing for bariatric surgery gave a
      substantial weight reduction without any significant negative metabolic effects.

PMID- 25069604
TI  - Repair of Achilles tendon defect with autologous ASCs engineered tendon in a
      rabbit model.
AB  - Adipose derived stem cells (ASCs) are an important cell source for tissue
      regeneration and have been demonstrated the potential of tenogenic
      differentiation in vitro. This study explored the feasibility of using ASCs for
      engineered tendon repair in vivo in a rabbit Achilles tendon model. Total 30
      rabbits were involved in this study. A composite tendon scaffold composed of an
      inner part of polyglycolic acid (PGA) unwoven fibers and an outer part of a net
      knitted with PGA/PLA (polylactic acid) fibers was used to provide mechanical
      strength. Autologous ASCs were harvested from nuchal subcutaneous adipose tissues
      and in vitro expanded. The expanded ASCs were harvested and resuspended in
      culture medium and evenly seeded onto the scaffold in the experimental group,
      whereas cell-free scaffolds served as the control group. The constructs of both
      groups were cultured inside a bioreactor under dynamic stretch for 5 weeks. In
      each of 30 rabbits, a 2 cm defect was created on right side of Achilles tendon
      followed by the transplantation of a 3 cm cell-seeded scaffold in the
      experimental group of 15 rabbits, or by the transplantation of a 3 cm cell-free
      scaffold in the control group of 15 rabbits. Animals were sacrificed at 12, 21
      and 45 weeks post-surgery for gross view, histology, and mechanical analysis. The
      results showed that short term in vitro culture enabled ASCs to produce matrix on
      the PGA fibers and the constructs showed tensile strength around 50 MPa in both
      groups (p > 0.05). With the increase of implantation time, cell-seeded constructs
      gradually form neo-tendon and became more mature at 45 weeks with histological
      structure similar to that of native tendon and with the presence of bipolar
      pattern and D-periodic structure of formed collagen fibrils. Additionally, both
      collagen fibril diameters and tensile strength increased continuously with
      significant difference among different time points (p < 0.05). In contrast, cell
      free constructs failed to form good quality tendon tissue with fibril structure
      observable only at 45 weeks. There were significant differences in both collagen
      fibril diameter and tensile strength between two groups at all examined time
      points (p < 0.05). The results of this study support that ASCs are likely to be a
      potential cell source for in vivo tendon engineering and regeneration. 

PMID- 25069605
TI  - Examining the use of telehealth in community nursing: identifying the factors
      affecting frontline staff acceptance and telehealth adoption.
AB  - AIMS: To examine frontline staff acceptance of telehealth and identify barriers
      to and enablers of successful adoption of remote monitoring for patients with
      Chronic Obstructive Pulmonary Disease and Chronic Heart Failure. BACKGROUND: The
      use of telehealth in the UK has not developed at the pace and scale anticipated
      by policy. Many existing studies report frontline staff acceptance as a key
      barrier, however data are limited and there is little evidence of the adoption of
      telehealth in routine practice. DESIGN: Case studies of four community health
      services in England that use telehealth to monitor patients with Chronic
      Obstructive Pulmonary Disease and Chronic Heart Failure. METHODS: Thematic
      analysis of qualitative interviews with 84 nursing and other frontline staff; and
      21 managers and key stakeholders; data collected May 2012-June 2013. FINDINGS:
      Staff attitudes ranged from resistance to enthusiasm, with varied opinions about
      the motives for investing in telehealth and the potential impact on nursing
      roles. Having reliable and flexible technology and dedicated resources for
      telehealth work were identified as essential in helping to overcome early
      barriers to acceptance, along with appropriate staff training and a partnership
      approach to implementation. Early successes were also important, encouraging
      staff to use telehealth and facilitating clinical learning and increased
      adoption. CONCLUSIONS: The mainstreaming of telehealth hinges on clinical 'buy
      in'. Where barriers to successful implementation exist, clinicians can lose faith
      in using technology to perform tasks traditionally delivered in person.
      Addressing barriers is therefore crucial if clinicians are to adopt telehealth
      into routine practice.

PMID- 25069606
TI  - A time course study about gene expression of post-thermal injury with DNA
      microarray.
AB  - BACKGROUND: Burn injury is one of the most common and devastating forms of trauma
      in daily life. However, the exact sequence of events after burn injury remains
      unknown. OBJECTIVE: This study aims to investigate gene expression alterations
      after burn injury. METHODS: Microarray data set GSE8056 was downloaded from the
      Gene Expression Omnibus (GEO) database, including 12 samples, equally distributed
      in four groups: normal skin tissue as control and damaged tissues 1-3 days after
      burn (early period); 4-7 days after burn (middle period); and more than 7 days
      after burn (late period). Packages in R language were utilized to pre-process the
      data and filter out the differentially expressed genes (DEGs). Functional
      annotation of all three groups of DEGs was conducted by using clusters of
      orthologous groups analysis. The DEGs shared by all three groups were picked out
      and analyzed with STRING to set up a protein-protein interaction network. CFinder
      was chosen to implement module analysis, and expression analysis systematic
      explorer was then adopted to reveal the dysfunctional pathways for each module.
      RESULTS: A total of 727, 782, and 445 DEGs were identified in the early, middle,
      and late period after burn, and 234 DEGs were identified as continually
      differentially expressed throughout all time periods, including genes encoding
      proinflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-1beta, and
      genes associated with cell proliferation. Three modules associated with cell
      proliferation and inflammatory responses were generated from the protein-protein
      interaction network. CONCLUSION: Our findings are beneficial for understanding
      the progression of the wound healing response after burn.

PMID- 25069607
TI  - Gastric leiomyosarcoma as a rare cause of gastric outlet obstruction and
      perforation: a case report.
AB  - BACKGROUND: Gastrointestinal stromal tumours are the most common mesenchymal
      malignancies of the gastrointestinal (GI) tract and gastric leiomyosarcoma
      represent 1-3% of gastric malignancies. CASE PRESENTATION: We report a case of a
      69-year-old black African man who presented with a rare cause of gastric outlet
      obstruction and duodenal perforation. A Billroth-II gastrectomy was performed and
      histology confirmed a gastric leiomyosarcoma. CONCLUSIONS: It is important to
      identify the gastric leiomyosarcoma which is a variant of the more common
      malignant gastrointestinal stromal tumours as the pathogenesis and management are
      currently well established. As the facilities for differentiating these are not
      easily available in resource-limited areas gastrointestinal stromal tumours may
      remain underdiagnosed and undertreated.

PMID- 25069608
TI  - On the structure of biomedical silver-doped phosphate-based glasses from
      molecular dynamics simulations.
AB  - First-principles and classical molecular dynamics simulations of undoped and
      silver-doped phosphate-based glasses with 50 mol% P2O5, 0-20 mol% Ag2O, and
      varying amounts of Na2O and CaO have been carried out. Ag occupies a distorted
      local coordination with a mean Ag-O bond length of 2.5 A and an ill-defined first
      coordination shell. This environment is shown to be distorted octahedral/trigonal
      bipyramidal. Ag-O coordination numbers of 5.42 and 5.54-5.71 are calculated for
      first-principles and classical methodologies respectively. A disproportionation
      in the medium-range phosphorus Q(n) distribution is explicitly displayed upon
      silver-doping via CaO substitution, approximating 2Q(2)->Q(1) + Q(3), but not on
      silver-doping via Na2O substitution. An accompanying increase in FWHM of the
      phosphorus to bridging oxygen partial pair-correlation function is strong
      evidence for a bulk structural mechanism associated with decreased dissolution
      rates with increased silver content. Experimentally, Ag2O <-> Na2O substitution
      is known to decrease dissolution and we show this to be a result of Ag's local
      bonding. 

PMID- 25069609
TI  - Interface deformations affect the orientation transition of magnetic ellipsoidal
      particles adsorbed at fluid-fluid interfaces.
AB  - Manufacturing new soft materials with specific optical, mechanical and magnetic
      properties is a significant challenge. Assembling and manipulating colloidal
      particles at fluid interfaces is a promising way to make such materials. We use
      lattice-Boltzmann simulations to investigate the response of magnetic ellipsoidal
      particles adsorbed at liquid-liquid interfaces to external magnetic fields. We
      provide further evidence for the first-order orientation phase transition
      predicted by Bresme and Faraudo [Journal of Physics: Condensed Matter, 2007, 19,
      375110]. We show that capillary interface deformations around the ellipsoidal
      particle significantly affect the tilt-angle of the particle for a given dipole
      field strength, altering the properties of the orientation transition. We propose
      scaling laws governing this transition, and suggest how to use these deformations
      to facilitate particle assembly at fluid-fluid interfaces. 

PMID- 25069611
TI  - Involvement of renal sympathetic nerve activation on the progression of ischemic
      acute kidney injury in the mouse.
AB  - Renal ischemia produces renal sympathoexcitation that is responsible for the
      development of ischemic acute kidney injury. The present study examined changes
      in the sympathetic nerve function in mice. Ischemic acute kidney injury was
      induced by occlusion of both renal pedicles. Renal ischemia/reperfusion increased
      blood urea nitrogen and plasma creatinine and expression of tyrosine hydroxylase,
      a rate-limiting enzyme for the biosynthesis of noradrenaline, in the kidney.
      Renal immunoreactivity of tyrosine hydroxylase was observed along with vessel and
      tubular structure both in the sham-operated and the ischemic acute kidney injury
      mice. The prominent morphological change was that tyrosine hydroxylase
      immunoreactivity was observed in the glomeruli of the ischemic acute kidney
      injury mice, whereas there are almost no tyrosine hydroxylase immunoreactivity
      signals in the glomeruli of the sham-operated mice. This tyrosine hydroxylase
      immunoreactivity in the glomeruli is colocalized with synapsin I immunoreactivity
      in the ischemic acute kidney injury mice. Intraperitoneal pretreatment with DSP-4
      (50 mg/kg) attenuated these changes induced by renal ischemia/reperfusion. These
      results suggest that morphological and functional changes of glomerulus
      adrenergic nerve terminal are involved in the pathophysiology of
      ischemia/reperfusion-induced ischemic acute kidney injury. 

PMID- 25069610
TI  - Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through
      modulating oxidative stress-responsive MAPK signaling.
AB  - BACKGROUND: Eotaxin proteins are a potential therapeutic target in treating the
      peribronchial eosinophilia associated with allergic airway diseases. Since
      inflammation is often associated with an increased generation of reactive oxygen
      species (ROS), oxidative stress is a mechanistically imperative factor in asthma.
      Astragalin (kaempferol-3-O-glucoside) is a flavonoid with anti-inflammatory
      activity and newly found in persimmon leaves and green tea seeds. This study
      elucidated that astragalin inhibited endotoxin-induced oxidative stress leading
      to eosinophilia and epithelial apoptosis in airways. METHODS: Airway epithelial
      BEAS-2B cells were exposed to lipopolysaccharide (LPS) in the absence and
      presence of 1-20 MUM astragalin. Western blot and immunocytochemical analyses
      were conducted to determine induction of target proteins. Cell and nuclear
      staining was also performed for ROS production and epithelial apoptosis. RESULTS:
      When airway epithelial cells were exposed to 2 MUg/ml LPS, astragalin nontoxic at
      <= 20 MUM suppressed cellular induction of Toll-like receptor 4 (TLR4) and ROS
      production enhanced by LPS. Both LPS and H2O2 induced epithelial eotaxin-1
      expression, which was blocked by astragalin. LPS activated and induced PLCgamma1,
      PKCbeta2, and NADPH oxidase subunits of p22phox and p47phox in epithelial cells
      and such activation and induction were demoted by astragalin or TLR4 inhibition
      antagonizing eotaxin-1 induction. H2O2-upregulated phosphorylation of JNK and p38
      MAPK was dampened by adding astragalin to epithelial cells, while this compound
      enhanced epithelial activation of Akt and ERK. H2O2 and LPS promoted epithelial
      apoptosis concomitant with nuclear condensation or caspase-3 activation, which
      was blunted by astragalin. CONCLUSIONS: Astragalin ameliorated oxidative stress
      associated epithelial eosinophilia and apoptosis through disturbing TLR4-PKCbeta2
      NADPH oxidase-responsive signaling. Therefore, astragalin may be a potent agent
      antagonizing endotoxin-induced oxidative stress leading to airway dysfunction and
      inflammation.

PMID- 25069612
TI  - Summaries for patients. Hormone treatment beginning near the onset of menopause.

PMID- 25069614
TI  - Bidirectional helical motility of cytoplasmic dynein around microtubules.
AB  - Cytoplasmic dynein is a molecular motor responsible for minus-end-directed cargo
      transport along microtubules (MTs). Dynein motility has previously been studied
      on surface-immobilized MTs in vitro, which constrains the motors to move in two
      dimensions. In this study, we explored dynein motility in three dimensions using
      an MT bridge assay. We found that dynein moves in a helical trajectory around the
      MT, demonstrating that it generates torque during cargo transport. Unlike other
      cytoskeletal motors that produce torque in a specific direction, dynein generates
      torque in either direction, resulting in bidirectional helical motility. Dynein
      has a net preference to move along a right-handed helical path, suggesting that
      the heads tend to bind to the closest tubulin binding site in the forward
      direction when taking sideways steps. This bidirectional helical motility may
      allow dynein to avoid roadblocks in dense cytoplasmic environments during cargo
      transport.

PMID- 25069613
TI  - Lkb1 is indispensable for skeletal muscle development, regeneration, and
      satellite cell homeostasis.
AB  - Serine/threonine kinase 11, commonly known as liver kinase b1 (Lkb1), is a tumor
      suppressor that regulates cellular energy metabolism and stem cell function.
      Satellite cells are skeletal muscle resident stem cells that maintain postnatal
      muscle growth and repair. Here, we used MyoD(Cre)/Lkb1(flox/flox) mice (called
      MyoD-Lkb1) to delete Lkb1 in embryonic myogenic progenitors and their descendant
      satellite cells and myofibers. The MyoD-Lkb1 mice exhibit a severe myopathy
      characterized by central nucleated myofibers, reduced mobility, growth
      retardation, and premature death. Although tamoxifen-induced postnatal deletion
      of Lkb1 in satellite cells using Pax7(CreER) mice bypasses the developmental
      defects and early death, Lkb1 null satellite cells lose their regenerative
      capacity cell-autonomously. Strikingly, Lkb1 null satellite cells fail to
      maintain quiescence in noninjured resting muscles and exhibit accelerated
      proliferation but reduced differentiation kinetics. At the molecular level, Lkb1
      limits satellite cell proliferation through the canonical AMP-activated protein
      kinase/mammalian target of rapamycin pathway, but facilitates differentiation
      through phosphorylation of GSK-3beta, a key component of the WNT signaling
      pathway. Together, these results establish a central role of Lkb1 in muscle stem
      cell homeostasis, muscle development, and regeneration.

PMID- 25069615
TI  - Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18
      1a overexpression in the brain.
AB  - BACKGROUND: An accumulating body of evidence points to the significance of
      neuroinflammation and immunogenetics in schizophrenia, and an imbalance of
      cytokines in the central nervous system (CNS) has been suggested to be associated
      with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model
      for the study of the alterations that may underlie the symptoms of subjects with
      schizophrenia. The aim of the present study was to elucidate the involvement of
      neuroinflammation and cytokine imbalance in this model. METHODS: Cytokines were
      evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by
      enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia
      and macrophage, astrocytic and neuroinflammation markers were quantified by
      western blot in the cortex and the striatum of Munc18-OE and WT mice. RESULTS:
      Each cytokine evaluated (Interferon-gamma (IFN-gamma), Tumor Necrosis Factor
      alpha (TNF-alpha), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher
      levels in the striatum of Munc18-OE mice than WT. Cortical TNF-alpha and IL-2
      levels were significantly lower in Munc18-OE mice than WT mice. The microglia and
      macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but
      no differences were observed in the striatum. Glial Fibrillary Acidic Protein
      (GFAP) and Nuclear Factor-kappaB (NF-kappaB)p65 levels were not different between
      the groups. Interleukin-1beta (IL-1beta) and IL-6 levels were beneath detection
      limits. CONCLUSIONS: The disrupted levels of cytokines detected in the brain of
      Munc18-OE mice was found to be similar to clinical reports and endorses study of
      this type for analysis of this aspect of the disorder. The lower CD11b expression
      in the cortex but not in the striatum of the Munc18-OE mice may reflect
      differences in physiological activity. The cytokine expression pattern observed
      in Munc18-OE mice is similar to a previously published model of schizophrenia
      caused by maternal immune activation. Together, these data suggest a possible
      role for an immune imbalance in this disorder.

PMID- 25069617
TI  - Cyclopropane pipecolic acids as templates for linear and cyclic peptidomimetics:
      application in the synthesis of an Arg-Gly-Asp (RGD)-containing peptide as an
      alphavbeta3 integrin ligand.
AB  - The synthesis and evaluation of substituted cyclopropane pipecolic acids (CPA) as
      conformationally restricted templates for linear and cyclic peptidomimetics is
      reported. A variety of differently substituted (poly)hydroxy- and amino-2
      azabicyclo[4.1.0]heptane-1-carboxylic acids were prepared by means of the Pd
      catalyzed methoxycarbonylation of suitably functionalized lactam-derived enol
      phosphates, followed by OH-directed cyclopropanation. CPAs were successfully
      introduced into a linear peptide sequence to assess the cis/trans isomerism about
      the pipecolic acid peptide bond, and in a cyclic peptidomimetic that bore the Arg
      Gly-Asp (RGD) sequence, which displayed nanomolar activity as antagonist of the
      alphavbeta3 integrin in M21 human melanoma cells. Thus, CPAs appear to be
      suitable for the generation of novel peptidomimetics for drug discovery.

PMID- 25069618
TI  - Three dimensional morphologic analysis of the lateral surface of the canine
      femur.
AB  - OBJECTIVES: Analyze the lateral plating surface of the femur to obtain bend and
      twist angles in dogs with non-chondrodystrophic phenotype. STUDY DESIGN:
      Retrospective computed tomography (CT) morphologic analysis. SAMPLE POPULATION:
      Historical cohort, hindlimb CT scans (n = 30). MATERIALS AND METHODS: The CT
      images of 30 normal femurs were uploaded to surgical planning software and 13
      points of interest and their respective bend/twist angles were identified on the
      lateral surfaces. Mean, standard deviation, coefficient of variation (CV), and
      range were calculated for each bend/twist angle. Hierarchal clustering and fast
      Fourier Analyses were used to segment the cohort. Distribution of age, breed,
      sex, and weight was evaluated between clusters with an exact Wilcoxon-Mann
      Whitney test. RESULTS: The CV of bending ranged from 17% to 46% and for twisting
      ranged from 21% to 58%. The greater trochanter was the most pronounced bend on
      the lateral surface of the femur (mean +/- SD 8.11 +/- 1.35 degrees , CV 17%),
      and the supracondylar region of the distal femur was the most marked twist (mean
      +/- SD 48.98 +/- 10.06 degrees , CV 21%). Although there were no differences
      between dogs in proximal femur anatomy, 2 clusters of 9 and 21 dogs each were
      identified due to differences in bend/twist angles in the distal femur. There was
      no difference between clusters for age (P = .85), breed (P = .62), and sex (P =
      .15); however, weight differed (P = .03) but was not predictive. CONCLUSION:
      Although distal femoral lateral surfaces varied sufficiently to result in 2
      population clusters, further analysis is needed to determine if the differences
      prevent using the mean bending and twisting parameters as a template for clinical
      applications.

PMID- 25069619
TI  - Obesity and pregnancy: a transversal study from a low-risk maternity.
AB  - BACKGROUND: Obesity is a public health problem and is increasing in all
      populations, including pregnant women. It influences maternal and neonatal
      outcomes; however, data are scarce in developing countries. We aimed to compare
      perinatal results between obese and non-obese pregnant women in a low-risk
      maternity. METHODS: Transversal study of 1,779 40-week-pregnancies from 2005 to
      2009 that completed a standard questionnaire with sociodemographic, obstetrical
      and neonatal variables and performed an ultrasound with amniotic fluid index
      (AFI) measurement and foetal vitality (FBP, non-stress test). They were analysed
      about their association with obesity on pregnancy. RESULTS: When compared with
      non-obese women, the group of obese patients had higher systolic (118.1 vs 109.2
      mmHg; p < 0.01) and diastolic (76.6 vs 70.4 mmHg; p < 0.01) pressure levels, AFI
      (12.52 vs. 9.61 cm; p = 0.02), presence of meconium on labour (20.52 vs. 14.67%;
      p = 0.02), birthweight (3602 vs. 3437 g; p < 0.01) and caesarean section (39.74
      vs. 29.98%, p < 0.01). CONCLUSIONS: Labour induction before 40 weeks in the
      antenatal period associated with foetal weight estimation should be considered as
      a recommendation for decreasing high percentages of caesarean delivery found in
      obese women.

PMID- 25069620
TI  - Continuous passive motion for preventing venous thromboembolism after total knee
      arthroplasty.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is a common form of orthopaedic
      surgery. Venous thromboembolism (VTE), which consists of deep venous thrombosis
      (DVT) and pulmonary embolism (PE), is a major and potentially fatal complication
      after TKA. The incidence of DVT after TKA is 40% to 80% and the incidence of PE
      is approximately 2%. It is generally agreed that thromboprophylaxis should be
      used in patients who undergo TKA. Both pharmacological and mechanical methods are
      used in the prevention of DVT. Pharmacological methods alter the blood
      coagulation profile and may increase the risk of bleeding complications. When
      pharmacological methods cannot be used the mechanical methods become crucial for
      VTE prophylaxis. Continuous passive motion (CPM) is provided through an external
      motorised device which enables a joint to move passively throughout a preset arc
      of motion. Despite the theoretical effectiveness and widespread use of CPM, there
      are still differing views on the effectiveness of CPM as prophylaxis against
      thrombosis after TKA. This is an update of the review first published in 2012.
      OBJECTIVES: The aim of this review was to determine the effectiveness of
      continuous passive motion (CPM) therapy for preventing venous thromboembolism
      (VTE) in patients after total knee arthroplasty (TKA). SEARCH METHODS: For this
      update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator
      searched the Specialised Register (last searched February 2014), CENTRAL (2014,
      Issue 1), Ovid MEDLINE (to week 1 February 2014) and EMBASE (to Week 07 2014).
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of CPM
      with control in preventing DVT or PE after TKA. People aged 18 years and older
      who had undergone TKA were included in this review. We excluded studies of
      patients who presented with DVT at baseline. The experimental and control groups
      received similar postoperative care and therapy other than the CPM. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed the citations
      retrieved by the search strategies for reports of relevant RCTs. They
      independently selected trials that satisfied the inclusion criteria, extracted
      data and undertook quality assessment. Effects were estimated as risk ratios
      (RRs), mean differences or standardised mean differences with 95% confidence
      intervals (CIs). Meta-analyses were performed using a fixed-effect model for
      continuous variables. Where heterogeneity existed (determined by the I(2)
      statistic) a random-effects model was used. MAIN RESULTS: Eleven RCTs involving
      808 participants met the inclusion criteria. The methodological quality of the
      included studies was variable and most of the predefined outcomes were reported
      by only one or two studies, therefore the quality of the evidence was low. Five
      studies with a total of 405 patients reported the incidence of DVT. In the CPM
      group (205 patients) 36 developed DVT (18%) compared to 29 (15%) in the control
      group (200 patients). The results of the meta-analysis showed no evidence that
      CPM had any effect on preventing VTE after TKA (RR 1.22, 95% CI 0.84 to 1.79).
      One trial (150 participants) did not find PE in any of the patients during
      hospitalisation or in the subsequent three months. PE was not reported in the
      other included studies. None of the trials reported deaths among the included
      participants. AUTHORS' CONCLUSIONS: There is not enough evidence from the
      available RCTs to conclude that CPM reduces VTE after TKA. We cannot assess the
      effect of CPM on mortality because no such events occurred amongst the
      participants of these trials. The quality of the evidence was low. The results
      are supported by only a small number of studies, most of which are of low to
      moderate quality.

PMID- 25069622
TI  - Fatal transmission of contagious caprine pleuropneumonia to an Arabian oryx (Oryx
      leucoryx).
AB  - Contagious caprine pleuropneumonia (CCPP) is an infectious respiratory disease
      mainly affecting domestic goats. As CCPP has never been documented in grazing
      antelopes (subfamily hippotraginae), they were not considered susceptible.
      Mycoplasma capricolum subspecies capripneumoniae (Mccp) was isolated from pleural
      liquid collected during the necropsy of a severely emaciated Arabian oryx with
      mild nasal discharge. The Mccp isolate was then genotyped using a multilocus
      sequence scheme; the sequence type was identical to the Mccp strain previously
      identified in a sand gazelle from a nearby enclosure. This case shows for the
      first time that members of the hippotraginae subfamily, here the Arabian oryx,
      can be affected by CCPP. In addition, genotyping shows that the oryx was most
      probably infected, at a distance, by sand gazelles. 

PMID- 25069621
TI  - Using technology to promote postpartum weight loss in urban, low-income mothers:
      a pilot randomized controlled trial.
AB  - OBJECTIVE: To examine the feasibility, acceptability, and initial efficacy of a
      technology-based weight loss intervention for urban, low-income mothers. METHODS:
      Eighteen obese, ethnic minority, socioeconomically disadvantaged mothers in the
      first year after childbirth were randomly assigned to either: 1) technology-based
      intervention, which included empirically supported behavior-change strategies,
      daily skills, and self-monitoring text messages with personalized feedback,
      biweekly counseling calls from a health coach, and access to a Facebook support
      group, or 2) usual-care control. RESULTS: After 14 weeks of treatment, the
      technology-based intervention participants had significantly greater weight loss
      (-2.9 +/- 3.6 kg) than usual care (0.5 +/- 2.3 kg; adjusted mean difference: -3.2
      kg, 95% confidence interval -6.2 to -0.1 kg, P = .04). One-third of intervention
      participants (3 of 9) and no control participants lost > 5% of their initial body
      weight at follow up. CONCLUSIONS AND IMPLICATIONS: Results suggest the potential
      for using technology to deliver a postpartum weight loss intervention among low
      income racial/ethnic minorities.

PMID- 25069623
TI  - Lowly pathogenic avian influenza (H9N2) infection in Plateau pika (Ochotona
      curzoniae), Qinghai Lake, China.
AB  - Avian influenza viruses (AIVs) are globally important contagions. Several
      domestic mammals can be infected with AIVs and may play important roles in the
      adaptation and transmission of these viruses in mammals, although the roles of
      wild mammals in the natural ecology of AIVs are not yet clear. Here, we performed
      a serological survey of apparently healthy Plateau pikas at Qinghai Lake in China
      to assess the prevalence of exposure to AIVs. Ninety-two of 293 (31%) of wild
      Plateau pikas possessed serum antibodies against a lowly pathogenic avian
      influenza (LPAI) H9N2 virus. Experimental inoculation of Plateau pikas with a
      LPAI H9N2 virus resulted in productive viral replication in respiratory tissues
      without prior adaptation. Our findings suggest that Plateau pikas represent a
      natural mammalian host to H9N2 AIVs and may play a role in the ongoing
      circulation of H9N2 viruses at Qinghai Lake in China. Surveillance for AIV
      infection in Plateau pika populations and other mammals that have close contact
      with the Plateau pikas should be considered. 

PMID- 25069624
TI  - Histones induce phosphatidylserine exposure and a procoagulant phenotype in human
      red blood cells.
AB  - BACKGROUND: Extracellular histones exert part of their prothrombotic activity
      through the stimulation of blood cells. Besides platelets, histones can bind to
      red blood cells (RBCs), which are important contributors to thrombogenesis, but
      little is known about the functional consequences of this interaction.
      OBJECTIVES: To evaluate the effect of histones on the procoagulant potential of
      human RBCs with particular regard to the expression of surface phosphatidylserine
      (PS). METHODS: PS exposure on human RBCs treated with a natural mixture of
      histones or recombinant individual histones was evaluated with fluorescein
      isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx
      in RBCs loaded with the calcium-sensitive fluorophore Fluo-4 AM was assessed with
      flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated
      with a purified prothrombinase assay and a one-stage plasma recalcification
      clotting test. RESULTS: Natural histones induced PS exposure on RBCs in a dose
      dependent manner, and neutralization or cleavage of histones by heparin or
      activated protein C, respectively, abolished PS externalization. H4 was mainly
      responsible for the stimulating activity of histones, whereas the other subtypes
      were almost ineffective. Similarly, natural histones and H4 induced influx of
      calcium into RBCs, whereas the other individual histones did not. Histone-induced
      exposure of PS on RBCs translated into increased prothrombinase complex-mediated
      prothrombin activation and accelerated fibrin formation in plasma. CONCLUSIONS:
      Histones induce RBCs to express a procoagulant phenotype through the
      externalization of PS. This finding provides new insights into the prothrombotic
      activity of extracellular histones.

PMID- 25069625
TI  - Comparison of wavefront aberrations in rabbit and human eyes.
AB  - BACKGROUND: The rabbit is one of the most common animal models used for
      preclinical safety evaluation of new cataract surgery and laser vision-correction
      technologies in ophthalmic research; however, the distributions of wavefront
      aberrations in rabbit eyes are unknown. The purpose of this study was to
      investigate the similarities and differences of wavefront aberrations between
      rabbit and human eyes. METHODS: Monochromatic wavefront aberrations of left and
      right eyes of 12 rabbits and 12 human subjects with normal vision were measured
      by a commercial aberrometer (WaveScan Wavefront System, Abbott Medical Optics
      Inc, California, USA). Comparison of wavefront aberrations in rabbit and human
      eyes is based on a 6.0 mm pupil. RESULTS: The rabbit eyes have an average
      spherical refraction of 1.51 +/- 0.83 D and a cylindrical refraction of -1.03 +/-
      0.63 D. The average spherical refractive error of the human eyes used in this
      study was -2.03 +/- 2.59 D with a cylindrical refraction of -1.27 +/- 1.01 D. The
      average wavefront error root-mean-square (RMS) from higher-order aberrations is
      0.34 MUm in rabbits (6.0 mm pupil), which is higher compared to the wavefront
      error RMS value of human eyes (0.26 MUm). The largest higher-order aberration in
      rabbit eyes is vertical coma (Z7, 0.19 +/- 0.16 MUm), whereas the largest higher
      order aberration in human eyes is spherical aberration (Z12, 0.07 +/- 0.13 MUm).
      Wavefront error RMS, vertical coma and some higher-order aberrations are
      significantly correlated between the right and left rabbit eye. CONCLUSION:
      Compared to wavefront aberrations in the human eye measured in this study, the
      rabbit eye has less refractive error but larger higher-order aberrations both in
      wavefront error RMS and some higher-order aberration terms. Similar to human
      eyes, wavefront error and some higher-order aberrations are significantly
      correlated between the right and left rabbit eye.

PMID- 25069626
TI  - Interface, interaction and integration: how people with chronic disease in
      Australia manage CAM and conventional medical services.
AB  - OBJECTIVES: To understand the extent to which conventional and complementary
      health care are integrated for CAM users with chronic conditions. METHODS: In
      depth interviews and a self-administered questionnaire were used to collect data
      on care-seeking, self-management and CAM use among people with type 2 diabetes
      and/or cardiovascular disease living in Victoria, Australia. RESULTS: Many
      participants reported regular, frequent and long-term use of CAM therapies to
      maintain their health or assist in the management of their chronic condition.
      They generally managed the interface between convention and complementary health
      care on their own, as the perceived or expressed negative attitudes of some
      doctors, or the belief that the doctor did not need to know, were barriers to the
      disclosure of CAM use. For a smaller group, there was interaction between
      conventional and CAM providers, which limited the extent of uncertainty and
      conflicting information being (mis)interpreted by consumers. CONCLUSIONS: Greater
      interaction between CAM and medical providers would be beneficial to consumers.
      Structural barriers, related to financing and service organization, need to be
      addressed. Attitudinal shifts of some health-care practitioners also need to be
      addressed, in the context of workforce development.

PMID- 25069628
TI  - Training health professionals in conducting maternal death reviews.
AB  - In countries where maternal death review (MDR) sessions are proposed as an
      intervention to improve quality of obstetric care, training focuses on the theory
      behind this method. However, experience shows that health staff lack confidence
      to apply the theory if they have not attended a practical training session. To
      address this problem, a training curriculum based on the new guidelines from the
      FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC)
      Initiative for preparing and conducting MDR sessions was designed and tested in
      Cameroon. This curriculum is competency-based and consists primarily of practical
      individual or group exercises. 

PMID- 25069627
TI  - Pain management following major intracranial surgery in pediatric patients: a
      prospective cohort study in three academic children's hospitals.
AB  - INTRODUCTION: Pain management following major intracranial surgery is often
      limited by a presumed lack of need and a concern that opioids will adversely
      affect postoperative outcome and interfere with the neurologic examination.
      Nevertheless, evidence in adults is accumulating that these patients suffer
      moderate to severe pain, and this pain is often under-treated. The purpose of
      this prospective, clinical observational cohort study was to assess the incidence
      of pain, prescribed analgesics, methods of analgesic delivery, and patient/parent
      satisfaction in pediatric patients undergoing cranial surgery at three major
      university children's hospitals. METHODS: After obtaining IRB and parental
      consent (and when applicable, patient assent), children who underwent cranial
      surgery for cancer, epilepsy, vascular malformations, and craniofacial
      reconstruction were studied. Neither intraoperative anesthetic management nor
      postoperative pain management was standardized, but were based on institutional
      routine. Patients were evaluated daily by a study investigator and by chart
      review for pain scores using age appropriate, validated tools (FLACC, Faces Pain
      Scale-Revised, Wong-Baker Faces Scale or Self-Report on a 0-10 scale), for
      patient/parent satisfaction using a subset of the NRC Picker satisfaction tool
      and in adolescents a modified QoR-40, and for the frequency, mode of
      administration, and type of analgesic provided. Finally, the incidence of opioid
      induced side effects, specifically nausea, vomiting, pruritus, altered level of
      consciousness, and need for emergency diagnostic radiologic studies for altered
      neurologic examination were recorded. Data are provided as mean +/- SD. RESULTS:
      Two hundred children (98:102 M:F), averaging 7.8 +/- 5.8 years old (range 2
      months-18.5 years) and 32.2 +/- 23.0 kg (range 4.5-111.6 kg) undergoing
      craniectomy (51), craniotomy (96), and craniofacial reconstruction (53) were
      studied. Despite considerable variation in mode and route of analgesic
      administration, there were no differences in average pain score, length of
      hospital stay, or parental satisfaction with care. Interestingly, opioid-induced
      side effects were not related to total daily opioid consumption, site of surgery,
      or method of opioid delivery. The most common side effect was vomiting. No
      patient developed respiratory depression or altered mental status secondary to
      analgesic therapy. Regardless of age or procedure, once eating, most patients
      were treated with oral oxycodone and/or acetaminophen. CONCLUSIONS: Despite
      considerable variation in modality and route of analgesic administration, there
      were no differences in average pain score, length of stay, or parental
      satisfaction with care. Pain scores were low, side effects were minimal, and
      parental satisfaction was high, providing equipoise for future blinded
      prospective randomized trials in this patient population.

PMID- 25069629
TI  - Outcomes of subsequent pregnancies after conservative treatment for placenta
      accreta.
AB  - OBJECTIVE: To estimate the association between conservative treatment for
      placenta accreta and subsequent pregnancy outcomes. METHODS: In a retrospective
      study, data were analyzed on women who received conservative treatment for
      placenta accreta (removal of the placenta with uterine preservation) at a
      tertiary hospital in Jerusalem, Israel, between 1990 and 2000. Data were
      collected on subsequent pregnancies and neonatal outcomes until 2010, and
      compared with those from a matched control group of women who did not have
      placenta accreta. RESULTS: A total of 134 women were included in both groups.
      Placenta accreta occurred in 62 (22.8%) of 272 subsequent deliveries in the study
      group for which data were available and 5 (1.9%) of 266 in the control group
      (relative risk [RR] 12.13; 95% confidence interval [CI] 4.95-29.69; P<0.001).
      Early postpartum hemorrhage occurred in 23 (8.6%) of 268 deliveries in the study
      group and 7 (2.6%) of 268 in the control group (RR 3.29; 95% CI 1.43-7.53;
      P<0.001). The odds ratio for recurrent placenta accreta in subsequent deliveries
      in the study group was 15.41 (95% CI 6.09-39.03; P<0.001). CONCLUSION: Although
      subsequent pregnancies after conservative treatment for placenta accreta were
      mostly successful, the risk of recurrent placenta accreta and postpartum
      hemorrhage is high in future deliveries.

PMID- 25069630
TI  - It is likely that the drinking of cold and room temperature water decreases
      cardiac workload.

PMID- 25069631
TI  - Pervasive transcription: illuminating the dark matter of bacterial
      transcriptomes.
AB  - The conventional view of transcription posits that mRNAs are generated from the
      coding DNA strand and are delineated by gene boundaries; however, recent reports
      have mapped transcription start sites to unexpected locations in bacterial
      genomes, including the non-coding strand. The resultant RNAs were previously
      dismissed as artefacts, but models that describe such events as 'pervasive
      transcription' are now gaining support. In this Opinion article, we discuss our
      current understanding of pervasive transcription, its genetic origin and its
      regulation. On the basis of existing observations, we propose that RNAs that
      result from pervasive transcription are more than 'transcriptional noise' and
      have important functions in gene regulation and genome evolution.

PMID- 25069632
TI  - A guide to handling missing data in cost-effectiveness analysis conducted within
      randomised controlled trials.
AB  - Missing data are a frequent problem in cost-effectiveness analysis (CEA) within a
      randomised controlled trial. Inappropriate methods to handle missing data can
      lead to misleading results and ultimately can affect the decision of whether an
      intervention is good value for money. This article provides practical guidance on
      how to handle missing data in within-trial CEAs following a principled approach:
      (i) the analysis should be based on a plausible assumption for the missing data
      mechanism, i.e. whether the probability that data are missing is independent of
      or dependent on the observed and/or unobserved values; (ii) the method chosen for
      the base-case should fit with the assumed mechanism; and (iii) sensitivity
      analysis should be conducted to explore to what extent the results change with
      the assumption made. This approach is implemented in three stages, which are
      described in detail: (1) descriptive analysis to inform the assumption on the
      missing data mechanism; (2) how to choose between alternative methods given their
      underlying assumptions; and (3) methods for sensitivity analysis. The case study
      illustrates how to apply this approach in practice, including software code. The
      article concludes with recommendations for practice and suggestions for future
      research.

PMID- 25069633
TI  - Fractionation and ecotoxicological implication of potentially toxic metals in
      sediments of three urban rivers and the Lagos Lagoon, Nigeria, West Africa.
AB  - The potential environmental impact of sediment-bound Cd, Cr, Cu, Pb and Zn in
      three trans-urban rivers in Lagos state and in the Lagos Lagoon was assessed by
      use of the modified Community Bureau of Reference (BCR) sequential extraction.
      The quality of the data was checked using BCR CRM 143R and BCR CRM 701. Good
      agreement was obtained between found and certified/indicative values. Of the
      rivers, the Odo-Iyaalaro, was generally the most contaminated and the Ibeshe the
      least. Higher concentrations of metals were generally found in the dry season
      compared to the wet season. Cadmium and Zn were released mostly in the acid
      exchangeable step of the sequential extraction, indicating that they have the
      greatest potential mobility and bioavailability of the analytes studied. Chromium
      and Cu were associated mainly with the reducible and oxidisable fractions, and Pb
      predominantly with the reducible and residual fractions. Sediments with the
      highest pseudototal analyte concentrations also released higher proportions of
      analytes earlier in the sequential extraction procedure. The study suggests that,
      during the dry season, potentially toxic metals (PTM) may accumulate in sediments
      in relatively labile forms that are released and can potentially be transported
      or bioaccumulate in the rainy season. Application of risk assessment codes and
      Hankanson potential risk indices indicated that Cd was the element of greatest
      concern in the Lagos Lagoon system. The study indicated that there is a need to
      strengthen environmental management and pollution control measures to reduce risk
      from PTM, but that even relatively simple strategies, such as seasonal
      restrictions on dredging and fishing, could be beneficial. 

PMID- 25069634
TI  - The meaning of surgeon's comfort in robotic surgery.

PMID- 25069635
TI  - One size does not fit all: cardiovascular health disparities as a function of
      ethnicity in Asian-American women.
AB  - OBJECTIVE: Although few studies have examined cardiovascular disease in Asian
      American subgroups separately, limited data in Asian Americans strongly suggest
      that some subgroups are at increased risk. The present study examined modifiable
      cardiovascular risk factor profiles as a function of Asian ethnicity. METHODS:
      This descriptive cross-sectional pilot study recruited Asian-American women
      (N=147) in northeast Florida including Cambodians (n=39), Chinese (n=36),
      Filipinos (n=49), and Vietnamese (n=23). Risk factors included blood pressure,
      body mass index, waist circumference and blood lipids. RESULTS: Filipino
      participants (41%) had >=4 risk factors compared to 21% Cambodian, 13% Vietnamese
      and 0% Chinese. The Chinese had significantly more participants (44%) with the
      absence of CVD risk factors compared to all other subgroups. Obesity rate (18%),
      mean BMI: 26 +/- 5 kg/m(2) and mean triglycerides (173 +/- 103 mg/dL) were
      highest in Filipinas (n=49). The Chinese (n=36) had a low rate (4%) of obesity
      with a mean BMI of 23 +/- 3 kg/m(2) and the least risk factors along with the
      lowest triglycerides (88 +/- 44 mg/dL). Cambodians (n=39; BMI of 24 +/- 3
      kg/m(2)) and Vietnamese (n=23; BMI: 22 +/- 3 kg/m(2)) had low rates of obesity
      with comparable rates of unhealthy lipids and hypertension as the Filipinas.
      CONCLUSIONS: Modifiable CVD risk factor profiles significantly differed as a
      function of ethnicity supporting the premise that Asian-American women cannot be
      categorized as one group and the traditional "one size fits all" prevention or
      treatment of CVD risk factors should be re-considered.

PMID- 25069636
TI  - Prophylactic tranexamic acid in parturients at low risk for post-partum
      haemorrhage: systematic review and meta-analysis.
AB  - Tranexamic acid is effective in reducing blood loss during various types of
      surgery and after trauma. No compelling evidence has yet been presented for post
      partum haemorrhage. A systematic literature search of relevant databases was
      performed to identify trials that assessed blood loss and transfusion incidence
      after tranexamic acid administration for post-partum haemorrhage. The random
      effects model was used for meta-analysis. Risk ratios (RRs) and weighted mean
      differences (WMDs) were calculated with 95% confidence intervals (CIs). Seven
      trials with a low risk of bias comparing tranexamic acid vs. placebo with a total
      of 1760 parturients were included in our systematic review and meta-analysis.
      Blood loss was significantly lower after tranexamic acid use (WMD -140.29 ml, 95%
      CI -189.64 to -90.93 ml; P<0.00001). Tranexamic acid reduced the risk for blood
      transfusions (RR 0.34, 95% CI 0.20-0.60, P=0.0001). The incidence of transfusions
      in the placebo group varied between 1.4% and 33%. When omitting the two trials
      with the highest incidence of transfusions, the RR was no longer significant.
      Additional uterotonics were necessary in the placebo groups; gastrointestinal
      adverse events were more common after tranexamic acid use. Only four cases of
      thrombosis were found, two each in the tranexamic acid and control groups.
      Tranexamic acid effectively reduced post-partum blood loss; the effect on the
      incidence of blood transfusions requires further studies. Only few trials
      observed adverse events including thromboembolic complications and seizures.

PMID- 25069637
TI  - Suppression of the TGF-beta/Smad signaling pathway and inhibition of hepatic
      stellate cell proliferation play a role in the hepatoprotective effects of
      curcumin against alcohol-induced hepatic fibrosis.
AB  - The hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis
      have rarely been discussed and its mechanisms of action in alcohol-induced liver
      disease remain unknown. In this study, serum alkaline phosphatase (ALP),
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were
      measured to assess hepatic function; histopathological and immunohistochemical
      observations were used to evaluate pathological and specific molecular changes in
      liver tissue and flow cytometry was used to detect the apoptosis in cultured
      hepatic stellate cells (HSCs), the major fibrogenic cells in the liver; PCR and
      western blot analysis were employed to evaluate the changes in the expression of
      molecules and signaling pathways. We demonstrate that curcumin alleviates alcohol
      induced hepatic fibrosis by affecting the HSCs. We found that the administration
      of curcumin inhibited alcohol-induced HSC proliferation and even induced HSC
      apoptosis by stimulating endoplasmic reticulum (ER) stress. We also found that by
      suppressing the transforming growth factor-beta (TGF-beta)/Smad signaling
      pathway, the administration of curcumin impaired the production of extracellular
      matrix proteins in alcohol-stimulated HSCs. These results indicate that curcumin
      exerts its hepatoprotective effects against alcohol-induced hepatic fibrosis by
      inhibiting the proliferation and inducing the apoptosis of HSCs by stimulating ER
      stress and deactivating HSCs by suppressing the TGF-beta/Smad signaling pathway. 

PMID- 25069638
TI  - Predicting who will undergo surgery after physiotherapy for female stress urinary
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: To predict who will undergo midurethral sling
      surgery (surgery) after initial pelvic floor muscle training (physiotherapy) for
      stress urinary incontinence in women. METHODS: This was a cohort study including
      women with moderate to severe stress incontinence who were allocated to the
      physiotherapy arm from a previously reported multicentre trial comparing initial
      surgery or initial physiotherapy in treating stress urinary incontinence.
      Crossover to surgery was allowed. RESULTS: Data from 198/230 women who were
      randomized to physiotherapy was available for analysis, of whom 97/198 (49 %)
      crossed over to surgery. Prognostic factors for undergoing surgery after
      physiotherapy were age <55 years at baseline (OR 2.87; 95 % CI 1.30-6.32), higher
      educational level (OR 3.28; 95 % CI 0.80-13.47), severe incontinence at baseline
      according to the Sandvik index (OR 1.77; 95 % CI 0.95-3.29) and Urogenital
      Distress Inventory; incontinence domain score (OR 1.03; per point; 95 % CI 1.01
      1.65). Furthermore, there was interaction between age <55 years and higher
      educational level (OR 0.09; 95 % CI 0.02-0.46). Using these variables we
      constructed a prediction rule to estimate the risk of surgery after initial
      physiotherapy. CONCLUSION: In women with moderate to severe stress incontinence,
      individual prediction for surgery after initial physiotherapy is possible, thus
      enabling shared decision making for the choice between initial conservative or
      invasive management of stress urinary incontinence.

PMID- 25069639
TI  - Knockdown of ubiquitin associated protein 2-like inhibits the growth and
      migration of prostate cancer cells.
AB  - The ubiquitin-proteasome system (UPS) is involved in the development of cancer in
      various functions. Inhibition of the ubiquitin-proteasome has been revealed to be
      a powerful therapeutic method for carcinoma. Ubiquitin associated protein 2-like
      (UBAP2L) is believed to be involved in the ubiquitin-proteasome pathway; however,
      the role of UBAP2L in human prostate cancer is still unknown. In the present
      study, we found that UBAP2L was expressed in a number of prostate carcinoma cell
      lines. Using lentiviral-mediated RNA interference (RNAi), we efficiently knocked
      down endogenous UBAP2L expression at the mRNA and protein levels. After UBAP2L
      disruption, the proliferation and colony formation ability were significantly
      reduced in the PC-3 and DU145 cells. Flow cytometric analysis showed that UBAP2L
      knockdown blocked cell cycle progression. Downregulation of UBAP2L inhibited the
      migration of PC-3 and DU145 cells, as determined by Transwell assay. Moreover,
      depletion of UBAP2L blocked the AMPKalpha, Bad and PRAS40 signaling pathways. In
      conclusion, our results suggest that UBAP2L may play a role in prostate cancer
      growth and metastasis, and knockdown of UBAP2L by RNAi may serve as a potential
      therapeutic approach for prostate cancer. 

PMID- 25069640
TI  - Danhong injection attenuates ischemia/reperfusion-induced brain damage which is
      associating with Nrf2 levels in vivo and in vitro.
AB  - Danhong injection, a Chinese Materia Medica standardized product extracted from
      Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is used extensively for
      the treatment of cerebrovascular diseases such as acutely cerebral infarction in
      clinic. In this study, we further investigated the mechanisms of Danhong
      injection on cerebral ischemia/reperfusion (I/R) damage relating to Nrf2/ARE
      signalling pathway in vivo and in vitro. For in vivo experiment, cerebral I/R
      injury was induced through middle cerebral artery occlusion. Rats were randomly
      divided into five groups: sham-operated group, I/R injury group, 6 mg/kg
      edaravone injection (positive control drug) group, 0.9 ml/kg Danhong injection
      (DHI-L) group, 1.8 ml/kg Danhong injection (DHI-H) group. The neurological score,
      cerebral infarction and brain edema were assessed while levels of superoxide
      dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in brain tissue were
      also evaluated. Transcription levels of nuclear factor erythroid 2-related factor
      2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1) were
      analysed by real-time polymerase chain reaction. For in vitro experiment, mouse
      Neuro-2A cells were wounded with H2O2 then cell viability and mRNA transcriptions
      levels of Nrf2, HO-1, NQO1 were detected. Protein expression level of Nrf2 was
      assayed by western blotting. The results showed that Danhong injection could
      ameliorate neurological score, cerebral infarction and brain edema. Also it can
      increase levels of SOD, GSH and decrease of MDA and upregulate expressions of
      Nrf2, HO-1, NQO1 in ischemic brain tissue in vivo. What's more, it increased the
      mRNA transcription of Nrf2 and HO-1 and upregulated protein expression of Nrf2 in
      vitro. These findings suggested that Danhong injection could prevent I/R-induced
      brain damage through activating Nrf2/ARE signaling pathway.

PMID- 25069642
TI  - Free radical scavenging activity and neuroprotective potentials of D138, one
      Cu(II)/Zn(II) Schiff-base complex derived from N,N'-bis(2
      hydroxynaphthylmethylidene)-1,3-propanediamine.
AB  - There is increasing evidence that free radicals play an important role in
      neuronal damages induced by diabetes mellitus or cerebral ischemia insults.
      Antioxidants with free radical scavenging activities have been shown to be
      beneficial and neuroprotective for these pathological conditions. Here, we report
      free radical scavenging activity and neuroprotective potential of D138, one
      copper(II)/zinc(II) Schiff-base complex derived from N,N'-2(2
      hydroxynaphthylmethylidene)-1,3-propanediamine. The data from three in vitro
      assays, 2,2-diphenyl-1-picrylhydrazyl assay, nitro blue tetrazolium assay and
      hydroxyl radical scavenging assay, indicated that D138 presented a potent free
      radical scavenging activity. The neuroprotective and antioxidative effects of
      D138 were further evaluated in vivo using bilateral common carotid artery
      occlusion (BCCAO) mouse model and streptozotocin (STZ) diabetic mouse model. Our
      results indicated that treatment of D138 significantly ameliorated the
      hippocampal neuronal damage and the oxidative stress levels in these animal
      models. Moreover, D138 also reversed the behavioral deficiencies induced by BCCAO
      or STZ, as assessed by Y-maze test and fear conditioning test. In conclusion, all
      these findings support that D138 exerts free radical scavenging and
      neuroprotective activities and has the potentials to be a potent therapeutic
      candidate for brain oxidative damage induced by cerebral ischemia or diabetes
      mellitus.

PMID- 25069644
TI  - Reply to the letter to the editor in response to: The correlation between
      prolonged corrected QT interval with the frequency of respiratory arrest,
      endotracheal intubation, and mortality in acute methadone overdose.

PMID- 25069641
TI  - Biomarker studies in multiple sclerosis: from proteins to noncoding RNAs.
AB  - Multiple sclerosis (MS) is a neuroimmunological disorder characterized by central
      nervous system demyelination, axonal injury and loss. Considering the complexity
      of its aetiopathogenesis, early diagnosis of MS and individualized management are
      challenging in clinical practice. As the pathophysiologic and pharmacological
      indicators, studies on biomarkers in MS are useful for early prediction and
      diagnosis, monitoring of disease activity and predicting treatment response. In
      this review, we will summarize recent development of biomarker studies in MS from
      protein molecules to noncoding RNAs. 

PMID- 25069643
TI  - NMDA glutamate receptor NR1, NR2A and NR2B expression and NR2B Tyr-1472
      phosphorylation in the lens.
AB  - Detailed parallels described between lens fiber cell and neuron morphology, sub
      cellular structure, and molecular biology include striking similarities in the
      ultrastructure of their vesicle transport machinery and the membrane protrusions
      that occur along the lateral surfaces of both cell types. alpha-Amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor (NMDA)
      glutamate receptors (AMPARs/NMDARs) are the predominant receptors in neurons.
      These receptors have fundamental roles in neuron morphogenesis as well as neuron
      physiology and dynamic cell signaling, and specifically at dendritic spines. As a
      result, AMPAR and NMDAR dysregulation underlies several primary neural disorders
      that have also shown epidemiological associations with cataract. Previously, we
      demonstrated AMPAR GluA1 and REST (RE-1 silencing transcription factor)-regulated
      GluA2 subunits are expressed in the lens, and showed C-terminal phospho-tyrosine
      GluA2, and striatal-enriched tyrosine phosphatase (STEP), as well as GluA2 Q/R
      RNA editing in lenses similar to neurons. Here, we demonstrated that REST
      regulated NMDAR NR1, NR2A, and NR2B are also expressed in lenses and localize
      predominantly in fiber cell membranes, consistent with REST transcription
      factors, as well as miR-124 and other REST gene targets identified in the lens.
      We also showed NR2B Tyr-1472 phosphorylation occurs in lens. These p-Tyr-GluA2
      and p-Tyr-NR2B phosphorylation events are linked with membrane insertion
      regulated by STEP. We next determined that NR1 transcripts that include exon 5
      are produced in lens consistent with Fox-1 RNA binding protein isoforms linked
      with this alternative splicing event, and shown to be expressed in lens as well
      as brain. These findings provide further evidence that fundamental neuronal
      morphogenetic programs, and hallmark neuronal gene expression and modes of
      regulation, are shared with elongated fiber cells of the lens.

PMID- 25069645
TI  - Homology modeling and molecular docking of human pituitary adenylate cyclase
      activating polypeptide I receptor.
AB  - Pituitary adenylate cyclase-activating peptide I receptor (PAC1R) is member of
      the B class of G protein-coupled seven-transmembrane receptors, with molecular
      functions associated with neural cell differentiation, regeneration and the
      inhibition of apoptosis. However, the integrity of the protein structure is
      difficult to be determined in vitro. In the present study, the physicochemical
      properties of PAC1R were analyzed, the extracellular, transmembrane and
      intracellular regions were constructed and a three-dimensional structure model of
      PAC1R was produced using extracellular loop region optimization and the energy
      minimization homology modeling method. Preliminary studies on the PAC1R protein
      and ligand interactions used a molecular docking method. The results indicated
      that the interaction sites of PAC1R were at Ile63, Ser100 and Gln105. These were
      the sites where the PAC1R combined with a hydrazide small molecule inhibitor.
      This study provides a theoretical basis for further studies on the model for the
      development of PAC1R target drugs.

PMID- 25069646
TI  - Statistical limits in sonographic estimation of birth weight.
AB  - PURPOSE: The accuracy of sonographic estimation of birth weight (EBW) is
      compromised by the precision of the biometrical measurements and the quality of
      the algorithms. This prospective study was to evaluate technical aspects to
      derive new equations for the EBW. METHODS: Three consecutive phases were carried
      out (1) to recruit a homogenous population, (2) to derive eight new algorithms
      using a multiple stepwise mathematical/statistical method, and (3) to test the
      accuracy of the developed equations. Only those patients with a singleton
      pregnancy who delivered within 48 h from the scan were considered for the
      analysis. RESULTS: The study population was made of 473 women. Four polynomial,
      two square root and two logarithmic algorithms were derived from a balanced study
      group of 200 women selected from the original study population. These formulas
      were subsequently applied and compared between them and showed a significant
      correlation with birth weight (p < 0.0001) and satisfactory statistical
      performances (r > 0.9), nevertheless they performed similarly to other equations
      previously published. CONCLUSIONS: The present findings define better the
      limitations associated with the intrinsic properties of algorithms and highlight
      that the possibility to improve the precision of sonographic measurements remains
      the only point at issue to increase the accuracy in the prediction of birth
      weight.

PMID- 25069647
TI  - Response to: an easy insertion procedure of Bakri balloon during cesarean section
      for placenta previa: use of Nelaton rubber catheter.

PMID- 25069648
TI  - High-sensitivity C-reactive protein as a novel marker in early diagnosis of
      ovarian torsion: an experimental study.
AB  - OBJECTIVE: To investigate the effect of ovarian torsion on plasma high
      sensitivity C reactive protein (hs-CRP) levels and to determine whether hs-CRP
      levels were a useful adjunct that could be used in the diagnosis of ovarian
      torsion. MATERIALS AND METHODS: Sixteen nulligravid 4-month-old female Wistar
      albino rats were randomly and equally allocated into two groups. Control group,
      sham operation (n = 8) group, and study group, ovarian torsion (n = 8) group.
      Ovarian torsion model was created using titanium vascular clips and vascular
      clips were kept for a 2-h period. Right ovaries were surgically removed at the
      end of the procedure in each group. Blood was sampled before and after operation
      to assess plasma hs-CRP levels. Ovarian histopathologic findings scores and
      plasma hs-CRP levels were evaluated. RESULTS: In study group, the mean plasma hs
      CRP level was significantly higher than that in the control group. (0.91 +/- 0.18
      vs. 0.39 +/- 0.06 mg/l, respectively, p < 0.001), following 2 h of ovarian
      torsion. Histologic examinations of the right ovary confirmed the torsion model.
      Histologic score of the specimens had higher scores for follicular cell
      degeneration (p = 0.002), vascular congestion (p = 0.002), inflammatory cell
      infiltration (p = 0.003), and hemorrhage (p < 0.001) in the study group. For the
      change in the plasma hs-CRP value for a cut-off value of >0.275 mg/l, sensitivity
      and specificity were calculated as 100 %. CONCLUSION: The measurement of hs-CRP
      in a rat model seems to be a valuable plasma marker in early detection and
      diagnosis of ovarian torsion. However, further clinical and experimental studies
      of a larger size are required.

PMID- 25069649
TI  - Antioxidant lactobacilli could protect gingival fibroblasts against hydrogen
      peroxide: a preliminary in vitro study.
AB  - Oxidative stress and tissue destruction are at the heart of periodontal diseases.
      The dental research area is geared toward the prevention of free radicals by
      nutrient antioxidants. Lactic acid bacteria (LAB) have recently attracted
      attention in alternative dental therapies. We aimed at highlighting the
      antioxidative property of Lactobacilli and Bifidobacterium strains and at
      determining their protective effect on gingival fibroblasts (GFs). Two
      Lactobacilli and 2 Bifidobacterium strains were screened for their
      exopolysaccharide (EPSs) production. Antioxidative assays were conducted by
      spectrophotometer analysis. Resistance to different concentrations of hydrogen
      peroxide (H2O2) was determined by the serial dilution technique. The protective
      effect of strains on GFs on hydrogen peroxide exposure was also examined by a new
      trypan blue exclusion assay method. Bifidobacterium breve A28 showed the highest
      EPS production (122 mg/l) and remarkable antioxidant activity, which were
      demonstrated by its ability to scavenge 72% alpha,alpha-diphenyl-1-picrylhydrazyl
      free radical and chelate 88% of iron ion, respectively. Inhibition of lipid
      peroxidation was determined as 71% for the A28 strain. We suggest that LAB with
      antioxidative activity could be a good natural therapy agent for periodontal
      disorders.

PMID- 25069650
TI  - Recombinant human thrombopoietin promotes platelet engraftment after
      haploidentical hematopoietic stem cell transplantation: a prospective randomized
      controlled trial.
AB  - Delayed platelet engraftment (DPE) is a common complication following allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). This phenomenon is also a
      predictor of increased treatment-related mortality and poor survival. Therefore,
      therapies that promote platelet engraftment to prevent DPE are needed. This
      prospective randomized controlled trial was designed to investigate whether
      recombinant human thrombopoietin (rhTPO), administered subcutaneously at a daily
      dose of 15,000 U from the first day after transplantation, promotes platelet
      engraftment after haploidentical HSCT. The cumulative incidence of platelet
      engraftment (platelet recovery to >=20 * 10(9)/L without transfusion support for
      seven consecutive days) on day 60 post-transplantation was significantly higher
      in the rhTPO group (n = 60) than in the control group (n = 60) (91.7 +/- 3.8 %
      vs. 74.5 +/- 5.8 %, P = 0.041). Additionally, the number of platelet transfusions
      from day 14 to day 60 was significantly lower in the rhTPO group than in the
      control group (4 +/- 5 vs. 7 +/- 9 Units, P = 0.018). No severe adverse effects
      were observed, with a median follow-up duration of 256 days (range, 48-586 days).
      The incidences of acute graft-versus-host disease (GVHD), chronic GVHD, and
      cytomegalovirus viremia and the probabilities of overall survival and disease
      free survival did not differ between the two groups. A multivariate analysis of
      all patients revealed that regardless of assignment to the rhTPO group or the
      control group (hazard ratio (HR) = 1.514; 95 % CI (1.024-2.238); P = 0.038), the
      number of total infused CD34(+) cells (HR = 1.304; 95 % CI (1.148-1.482); P <
      0.001) and slower neutrophil engraftment (HR = 2.777; 95 % CI (1.841-4.189); P <
      0.001) were associated with platelet engraftment. In conclusion, rhTPO promotes
      platelet engraftment and safely reduces the requirement for platelet transfusion
      in patients after unmanipulated haploidentical HSCT. This trial was registered
      with the Chinese Clinical Trial Registry ( www.chictr.org ) as ChiCTR-TRC
      11001774. http://www.chictr.org/cn/proj/show.aspx?proj=2132 . 

PMID- 25069651
TI  - Principal component model for maternal ECG extraction in fetal QRS detection.
AB  - Fetal cardiac monitoring using noninvasive abdominal leads can provide important
      information on fetal well-being. However, extraction of fetal electrocardiogram
      (fECG) from abdominal signals is often problematic because of the higher
      amplitude maternal ECG (mECG). The aim of this study was to introduce a principal
      component model for removing the maternal ECG from abdominal signals. The
      proposed method removes mECG waveforms with high accuracy even though abdominal
      movements cause morphological deviation to mECG complexes. The method can be used
      for single or multi-lead measurements. The proposed method was tested using 175 1
      min long abdominal measurements with fetal QRS annotation markers acquired from a
      fetal scalp electrode. Using the presented mECG removing algorithm and matched
      filtering based fQRS detector, 95% sensitivity for fQRS detection and 4.84 ms RMS
      error for fetal RR-interval estimation were acquired. 

PMID- 25069654
TI  - Understimulation of Cerebellum in Asperger's Syndrome: A Personal Perspective.

PMID- 25069653
TI  - Transcript length mediates developmental timing of gene expression across
      Drosophila.
AB  - The time required to transcribe genes with long primary transcripts may limit
      their ability to be expressed in cells with short mitotic cycles, a phenomenon
      termed intron delay. As such short cycles are a hallmark of the earliest stages
      of insect development, we tested the impact of intron delay on the Drosophila
      developmental transcriptome. We find that long zygotically expressed genes show
      substantial delay in expression relative to their shorter counterparts, which is
      not observed for maternally deposited transcripts. Patterns of RNA-seq coverage
      along transcripts show that this delay is consistent with their inability to
      completely transcribe long transcripts, but not with transcriptional initiation
      based regulatory control. We further show that highly expressed zygotic genes
      maintain compact transcribed regions across the Drosophila phylogeny, allowing
      conservation of embryonic expression patterns. We propose that the physical
      constraints of intron delay affect patterns of expression and the evolution of
      gene structure of a substantial portion of the Drosophila transcriptome. 

PMID- 25069655
TI  - Cognitive behavioral therapy (brief vs standard duration) for schizophrenia.
AB  - There is some evidence from research that suggests that cognitive behavioral
      therapy for psychosis (CBTp) might offer some advantage if offered in combination
      with pharmacological treatments for people with schizophrenia. There are,
      however, limitations in its provision due to available resource and training
      issues. Brief forms of CBTp might be an alternative in settings with limited
      resources. Brief therapies have shown to be as effective as standard therapies
      for some nonpsychotic disorders. There is some evidence in favor of brief CBTp.
      We wanted to review the effects of brief CBTp for people with schizophrenia
      compared with standard CBTp. We searched the Cochrane Schizophrenia Group's
      Trials Register for randomized controlled trials (RCTs) involving adults with
      schizophrenia or related disorders, comparing brief cognitive behavioral therapy
      for people with psychosis vs standard CBTp. We found only 7 studies which used a
      brief version of CBTp, but no study compared brief CBTp with CBTp of standard
      duration. There is a need for RCTs which compare brief with standard CBTp. This
      review also highlighted the need for setting standard criteria for CBTp dose. For
      this review, we considered brief CBTp to be delivered within 4 months and using 6
      10 sessions. 

PMID- 25069656
TI  - The exam scam.

PMID- 25069657
TI  - Guerrillas in the mist: how I met a Colombian rebel leader.

PMID- 25069652
TI  - Massive expansion of Ubiquitination-related gene families within the Chlamydiae.
AB  - Gene loss, gain, and transfer play an important role in shaping the genomes of
      all organisms; however, the interplay of these processes in isolated populations,
      such as in obligate intracellular bacteria, is less understood. Despite a general
      trend towards genome reduction in these microbes, our phylogenomic analysis of
      the phylum Chlamydiae revealed that within the family Parachlamydiaceae, gene
      family expansions have had pronounced effects on gene content. We discovered that
      the largest gene families within the phylum are the result of rapid gene birth
      and-death evolution. These large gene families are comprised of members harboring
      eukaryotic-like ubiquitination-related domains, such as F-box and BTB-box
      domains, marking the largest reservoir of these proteins found among bacteria. A
      heterologous type III secretion system assay suggests that these proteins
      function as effectors manipulating the host cell. The large disparity in copy
      number of members in these families between closely related organisms suggests
      that nonadaptive processes might contribute to the evolution of these gene
      families. Gene birth-and-death evolution in concert with genomic drift might
      represent a previously undescribed mechanism by which isolated bacterial
      populations diversify. 

PMID- 25069658
TI  - Studies on floral nectary, tepals' structure, and gynostemium morphology of
      Epipactis palustris (L.) Crantz (Orchidaceae).
AB  - The lip of Epipactis palustris consists of two movably joined parts: the basal
      part (hypochile) with central broad isthmus and epichile with callus. The
      analysis of flowers provides strong evidence to conclude that the whole surface
      of lip callus and abaxial side of isthmus are secretory. The exudation at first
      appears on callus, at early stages, later on isthmus. It could be a strategy to
      prolong the emission of volatile substances and nectar, and this means to prolong
      luring pollinators. The results from transmission electron microscopy (TEM)
      support this conclusion. The plastids noted in callus were without starch,
      whereas the isthmus' cells contained partly hydrolyzed starch. Some plastids,
      noted in callus, had polymorphic shapes, which were often related to a starch
      reduction. During the depletion of starch in callus cells, the number of
      plastoglobuli within the plastids increased, and also lipid bodies appeared in
      the cytoplasm whereas, in isthmus cells, proplastids with phytoferritin were
      noted. The endoplasmic reticulum was in contact with plasmalemma, and the
      vesicles were fusing with plasmalemma in secretory cells of callus and isthmus,
      which is a way of granulocrine secretion. The cross-sections of sepals revealed
      that abaxial epidermis was tomentose, with stomata at the top of substomatal
      cavities. The pollen grains adhering to the rostellum-viscidium prove previous
      ecological observations that the rostellum-viscidium is not a barrier preventing
      self-pollination. 

PMID- 25069660
TI  - Skin cancer prevention campaign aimed at beachgoers on the Costa del Sol
      (southern Spain).
AB  - BACKGROUND: Sunbathing on the beach is one of the main risks for skin cancer.
      OBJECTIVE: In the summer of 2010, a skin cancer prevention campaign aimed at
      beachgoers was undertaken on the western Costa del Sol (southern Spain). METHODS:
      The campaign took place on beaches during July and August. A multicomponent
      intervention was conducted by a dermatologist and other healthcare professionals,
      including: (1) interviews about risk factors and sun protection habits; (2) full
      skin examination using dermoscopy; (3) health advice plus educational brochure;
      (4) sunscreen workshop plus free samples; and (5) survey about satisfaction and
      behavioral intentions. A journalism and health prize was offered to encourage
      mass media coverage. RESULTS: Four hundred and seven beachgoers (56% tourists)
      were recruited during the campaign, mean age 45 years. Most of the participants
      reported high-risk sun exposure and revealed high rates of clinically suspicious
      lesions of skin cancer (8.1%), melanoma (2.9%), actinic keratosis (10.2%), and
      atypical nevus (7.6%). The campaign was highly appreciated by the participants
      and followed not only by local but also regional and national media. CONCLUSION:
      Beachgoers are a strategic target to prevent skin cancer. Beaches are also
      suitable places to develop a skin cancer prevention campaign, allowing direct
      access to the high-risk population for surveying, health behavior education, and
      screening. Several keys may be useful to optimize results as the design of a
      personalized intervention of proven efficacy, provision of a trained healthcare
      team, and development of an attractive strategy for the mass media.

PMID- 25069661
TI  - Analysis of phytosterols and phytostanols in enriched dairy products by Fast gas
      chromatography with mass spectrometry.
AB  - A Fast gas chromatography and mass spectrometry method for plant sterols/stanols
      analysis was developed, using a short capillary gas chromatography column (10 m *
      0.1 mm internal diameter * 0.1 MUm film thickness) coated with 5% diphenyl
      polysiloxane. A silylated mixture of the main plant sterols/stanols standards
      (beta-sitosterol, campesterol, stigmasterol, campestanol, sitostanol) was well
      separated in 1.5 min, with a good peak resolution (>1.4, determined on a critical
      chromatographic peak pair (beta-sitosterol and sitostanol)), repeatability
      (<13%), and sensitivity (<0.017 ng/mL). The suitability of this Fast
      chromatography method was tested on plant sterols/stanols-enriched dairy products
      (yogurt and milk), which were subjected to lipid extraction, cold saponification,
      and silylation prior to injection. The analytical performance (sensitivity <
      0.256 ng/mL and repeatability < 10.36%) and significant reduction of the analysis
      time and consumables demonstrate that Fast gas chromatography-mass spectrometry
      method could be also employed for the plant sterols/stanols analysis in
      functional dairy products. 

PMID- 25069662
TI  - Therapeutic potential of larval excretory/secretory proteins of the pig whipworm
      Trichuris suis in allergic disease.
AB  - BACKGROUND: Gastrointestinal nematodes are currently being evaluated as a novel
      therapeutic in the treatment of chronic human inflammatory disorders, due to
      their unique ability to induce immunoregulatory pathways in their hosts. In
      particular, administration of ova from the pig whipworm Trichuris suis (T. suis;
      TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune
      disorders. Despite these advances, the biological pathways through which TSO
      therapy modulates the host immune system in the context of human disease remain
      undefined. METHODS: We characterized the dominant proteins present in the
      excretory/secretory (E/S) products of first-stage (L1) T. suis larvae (Ts E/S)
      using LC-MS/MS analysis and examined the immunosuppressive properties of whole
      larval Ts E/S in vitro and in a murine model of allergic airway disease. RESULTS:
      Administration of larval Ts E/S proteins in vivo during the allergen
      sensitization phase was sufficient to suppress airway hyperreactivity,
      bronchiolar inflammatory infiltrate and allergen-specific IgE production. Three
      proteins in larval Ts E/S were unambiguously identified. The immunomodulatory
      function of larval Ts E/S was found to be partially dependent on the
      immunoregulatory cytokine IL-10. CONCLUSIONS: Taken together, these data
      demonstrate that the released proteins of larval T. suis have significant
      immunomodulatory capacities and efficiently dampen allergic airway
      hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins
      should be exploited for the treatment of human allergic disorders.

PMID- 25069659
TI  - Targeting Hsp90 and its co-chaperones to treat Alzheimer's disease.
AB  - INTRODUCTION: Alzheimer's disease, characterized by the accumulation of
      hyperphosphorylated tau and beta amyloid (Abeta), currently lacks effective
      treatment. Chaperone proteins, such as the heat shock protein (Hsp) 90, form
      macromolecular complexes with co-chaperones, which can regulate tau metabolism
      and Abeta processing. Although small molecule inhibitors of Hsp90 have been
      successful at ameliorating tau and Abeta burden, their development into drugs to
      treat disease has been slow due to the off- and on-target effects of this
      approach as well as challenges with the pharmacology of current scaffolds. Thus,
      other approaches are being developed to improve these compounds and to target co
      chaperones of Hsp90 in an effort to limit these liabilities. AREAS COVERED: This
      article discusses the most current developments in Hsp90 inhibitors including
      advances in blood-brain barrier permeability, decreased toxicity and homolog
      specific small-molecule inhibitors. In addition, we discuss current strategies
      targeting Hsp90 co-chaperones rather than Hsp90 itself to reduce off-target
      effects. EXPERT OPINION: Although Hsp90 inhibitors have proven their efficacy at
      reducing tau pathology, they have yet to meet with success in the clinic. The
      development of Hsp90/tau complex-specific inhibitors and further development of
      Hsp90 co-chaperone-specific drugs should yield more potent, less toxic
      therapeutics.

PMID- 25069663
TI  - LeuO enhances butyrate-induced virulence expression through a positive regulatory
      loop in enterohaemorrhagic Escherichia coli.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) causes bloody diarrhoea and other
      severe symptoms such as haemorrhagic uraemic syndrome. The expression of
      virulence genes on the locus for enterocyte effacement (LEE) and associated genes
      is regulated by a variety of factors, including transcriptional regulators and
      environmental signals. Butyrate, one of the major short-chain fatty acids present
      in the intestine, enhances expression of LEE genes and flagella biosynthesis
      genes in EHEC O157:H7, resulting in increased bacterial adherence and motility.
      Here, we show that expression of the leuO gene, which encodes a LysR-type
      transcriptional regulator, is enhanced by butyrate via Lrp, which is also
      necessary for butyrate-induced responses of LEE genes. LeuO expression induces
      prolonged activation of the promoter of LEE1 operon, including the ler gene, as
      well as virulence mechanisms such as microcolony formation. Activation of the
      LEE1 promoter by LeuO depends on another regulator, called Pch. The response of
      the leuO promoter to butyrate requires two virulence regulators, Pch and Ler, in
      addition to Lrp. Pch, Ler and Lrp bind the upstream region of the leuO promoter.
      Thus, leuO is involved in butyrate-enhanced expression of LEE genes through a
      positive feedback mechanism, but its expression and action on the LEE1 promoter
      are dependent on the virulence regulators Pch and Ler. 

PMID- 25069664
TI  - Well-being, health and fitness of children who use wheelchairs: feasibility study
      protocol to develop child-centred 'keep-fit' exercise interventions.
AB  - AIM: To undertake the pre-clinical and modelling phases of the Medical Research
      Council complex intervention framework to underpin development of child-centred
      'keep-fit', exercise and physical activity interventions for children and young
      people who use wheelchairs. BACKGROUND: Children who use wheelchairs face many
      barriers to participation in physical activity, which compromises fitness,
      obesity, well-being and health. 'Keep-fit' programmes that are child-centred and
      engaging are urgently required to enhance participation of disabled children and
      their families as part of a healthy lifestyle. Nurses will likely be important in
      promoting and monitoring 'keep-fit' intervention(s) when implemented in the
      community. DESIGN: Mixed-method (including economic analysis) feasibility study
      to capture child and family preferences and keep-fit needs and to determine
      outcome measures for a 'keep-fit' intervention. METHODS: The study comprises
      three stages. Stage 1 includes a mixed-method systematic review of effectiveness,
      cost effectiveness and key stakeholder views and experiences of keep-fit
      interventions, followed by qualitative interviews with children, young people and
      their parents to explore preferences and motivations for physical activity. Stage
      2 will identify standardized outcome measures and test their application with
      children who use wheelchairs to obtain baseline fitness data. Options for an
      exercise-based keep-fit intervention will then be designed based on Stage 1 and 2
      findings. In stage 3, we will present intervention options for feedback and
      further refinement to children and parents/carers in focus groups. (Project
      funded October 2012). DISCUSSION: At completion, this study will lead to the
      design of the intervention and a protocol to test its efficacy.

PMID- 25069666
TI  - Urinary potassium excretion: can it predict the onset of hypertension?

PMID- 25069665
TI  - Novel mechanism of blood pressure regulation by forkhead box class O1-mediated
      transcriptional control of hepatic angiotensinogen.
AB  - The renin-angiotensin system is a major determinant of blood pressure regulation.
      It consists of a cascade of enzymatic reactions involving 3 components:
      angiotensinogen, renin, and angiotensin-converting enzyme, which generate
      angiotensin II as a biologically active product. Angiotensinogen is largely
      produced in the liver, acting as a major determinant of the circulating renin
      angiotensin system, which exerts acute hemodynamic effects on blood pressure
      regulation. How the expression of angiotensinogen is regulated is not completely
      understood. Here, we hypothesize that angiotensinogen is regulated by forkhead
      transcription factor forkhead box class O1 (Foxo1), an insulin-suppressed
      transcription factor, and thereby controls blood pressure in mice. We generated
      liver-specific Foxo1 knockout mice, which exhibited a reduction in plasma
      angiotensinogen and angiotensin II levels and a significant decrease in blood
      pressure. Using hepatocyte cultures, we demonstrated that overexpression of Foxo1
      increased angiotensinogen expression, whereas hepatocytes lacking Foxo1
      demonstrated a reduction of angiotensinogen gene expression and partially
      impaired insulin inhibition on angiotensinogen gene expression. Furthermore,
      mouse angiotensinogen prompter analysis demonstrated that the angiotensinogen
      promoter region contains a functional Foxo1-binding site, which is responsible
      for both Foxo1 stimulation and insulin suppression on the promoter activity.
      Together, these data demonstrate that Foxo1 regulates hepatic angiotensinogen
      gene expression and controls plasma angiotensinogen and angiotensin II levels,
      modulating blood pressure control in mice. 

PMID- 25069667
TI  - Differences in cell-type-specific responses to angiotensin II explain cardiac
      remodeling differences in C57BL/6 mouse substrains.
AB  - Despite indications that hearts from the C57BL/6N and C57BL/6J mouse substrains
      differ in terms of their contractility and their responses to stress-induced
      overload, no information is available about the underlying molecular and cellular
      mechanisms. We tested whether subacute (48 hours) and chronic (14 days)
      administration of angiotensin II (500 ng/kg per day) had different effects on the
      left ventricles of male C57BL/6J and C57BL/6N mice. Despite higher blood pressure
      in C57BL/6J mice, chronic angiotensin II induced fibrosis and increased the left
      ventricular weight/body weight ratio and cardiac expression of markers of left
      ventricular hypertrophy to a greater extent in C57BL/6N mice. Subacute
      angiotensin II affected a greater number of cardiac genes in C57BL/6N than in
      C57BL/6J mice. Some of the most prominent differences were observed for markers
      of (1) macrophage activation and M2 polarization, including 2 genes (osteopontin
      and galectin-3) whose inactivation was reported as sufficient to prevent
      angiotensin II-induced myocardial fibrosis; and (2) fibroblast activation. These
      differences were confirmed in macrophage- and fibroblast-enriched populations of
      cells isolated from the hearts of experimental mice. When testing F2 animals, the
      amount of connective tissue present after chronic angiotensin II administration
      did not cosegregate with the inactivation mutation of the nicotinamide nucleotide
      transhydrogenase gene from C57BL/6J mice, thus discounting its possible
      contribution to differences in cardiac remodeling. However, expression levels of
      osteopontin and galectin-3 were cosegregated in hearts from angiotensin II
      treated F2 animals and may represent endophenotypes that could facilitate the
      identification of genetic regulators of the cardiac fibrogenic response to
      angiotensin II. 

PMID- 25069668
TI  - Effective arterial elastance is insensitive to pulsatile arterial load.
AB  - Effective arterial elastance (E(A)) was proposed as a lumped parameter that
      incorporates pulsatile and resistive afterload and is increasingly being used in
      clinical studies. Theoretical modeling studies suggest that E(A) is minimally
      affected by pulsatile load, but little human data are available. We assessed the
      relationship between E(A) and arterial load determined noninvasively from central
      pressure-flow analyses among middle-aged adults in the general population
      (n=2367) and a diverse clinical population of older adults (n=193). In a separate
      study, we investigated the sensitivity of E(A) to changes in pulsatile load
      induced by isometric exercise (n=73). The combination of systemic vascular
      resistance and heart rate predicted 95.6% and 97.8% of the variability in E(A)
      among middle-aged and older adults, respectively. E(A) demonstrated a quasi
      perfect linear relationship with the ratio of systemic vascular resistance/heart
      period (middle-aged adults, R=0.972; older adults, R=0.99; P<0.0001). Aortic
      characteristic impedance, total arterial compliance, reflection magnitude, and
      timing accounted together for <1% of the variability in E(A) in either middle
      aged or older adults. Despite pronounced changes in pulsatile load induced by
      isometric exercise, changes in E(A) were not independently associated with
      changes pulsatile load but were rather a nearly perfect linear function of the
      ratio of systemic vascular resistance/heart period (R=0.99; P<0.0001). Our
      findings demonstrate that E(A) is simply a function of systemic vascular
      resistance and heart rate and is negligibly influenced by (and insensitive to)
      changes in pulsatile afterload in humans. Its current interpretation as a lumped
      parameter of pulsatile and resistive afterload should thus be reassessed.

PMID- 25069669
TI  - Visit-to-visit variability of blood pressure and cardiovascular disease and all
      cause mortality: a systematic review and meta-analysis.
AB  - Visit-to-visit variability of blood pressure (BP) has been associated with
      cardiovascular disease (CVD) and mortality in some but not all studies. We
      conducted a systematic review and meta-analysis to examine the association
      between visit-to-visit variability of BP and CVD and all-cause mortality. Medical
      databases were searched through June 4, 2014, for studies meeting the following
      eligibility criteria: adult participants; BP measurements at >=3 visits; follow
      up for CVD, coronary heart disease, stroke, or mortality outcomes; events
      confirmed via database, death certificate, or event ascertainment committee; and
      adjustment for confounders. Data were extracted by 2 reviewers and pooled using a
      random-effects model. Overall, 8870 abstracts were identified of which 37
      studies, representing 41 separate cohorts, met inclusion criteria. Across
      studies, visit-to-visit variability of systolic BP and diastolic BP showed
      significant associations with outcomes in 181 of 312 (58.0%) and 61 of 188
      (32.4%) analyses, respectively. Few studies provided sufficient data for pooling
      risk estimates. For each 5 mm Hg higher SD of systolic BP, the pooled hazard
      ratio for stroke across 7 cohorts was 1.17 (95% confidence interval [CI], 1.07
      1.28), for coronary heart disease across 4 cohorts was 1.27 (95% CI, 1.07-1.51),
      for CVD across 5 cohorts was 1.12 (95% CI, 0.98-1.28), for CVD mortality across 5
      cohorts was 1.22 (95% CI, 1.09-1.35), and for all-cause mortality across 4
      cohorts was 1.20 (95% CI, 1.05-1.36). In summary, modest associations between
      visit-to-visit variability of BP and CVD and all-cause mortality are present in
      published studies. However, these findings are limited by the small amount of
      data available for meta-analysis. 

PMID- 25069670
TI  - Elimination of bioweapons agents from forensic samples during extraction of human
      DNA.
AB  - Collection of DNA for genetic profiling is a powerful means for the
      identification of individuals responsible for crimes and terrorist acts. Biologic
      hazards, such as bacteria, endospores, toxins, and viruses, could contaminate
      sites of terrorist activities and thus could be present in samples collected for
      profiling. The fate of these hazards during DNA isolation has not been thoroughly
      examined. Our goals were to determine whether the DNA extraction process used by
      the Royal Canadian Mounted Police eliminates or neutralizes these agents and if
      not, to establish methods that render samples safe without compromising the human
      DNA. Our results show that bacteria, viruses, and toxins were reduced to
      undetectable levels during DNA extraction, but endospores remained viable.
      Filtration of samples after DNA isolation eliminated viable spores from the
      samples but left DNA intact. We also demonstrated that contamination of samples
      with some bacteria, endospores, and toxins for longer than 1 h compromised the
      ability to complete genetic profiling.

PMID- 25069671
TI  - Association between retinol-binding protein 4 and polycystic ovary syndrome: a
      meta-analysis.
AB  - Studies have examined the association between retinol-binding protein 4 (RBP4)
      and polycystic ovary syndrome (PCOS). However, the results have been
      inconsistent. To investigate the association between RBP4 and PCOS, we performed
      a meta-analysis. The Cochrane Library, MEDLINE, the ISI Web of Science, and
      EMBASE were searched to identify all of the studies that examined the
      relationship between circulating RBP4 levels and PCOS. Standard mean difference
      (SMD) values and 95% confidence interval (CI) were estimated and pooled using
      meta-analysis methodology. A total of seven studies were involved in the meta
      analysis, which included a total of 636 subjects (260 controls and 376 patients
      with PCOS). The RBP4 level was higher in PCOS patients than in non-PCOS patients
      (random effects MD (95% CI)=0.69, [0.20, 1.18], P=0.006). However, the RBP4 level
      was not higher in nonobese PCOS patients than in nonobese controls (random
      effects MD (95% CI)=0.38, [-0.21, 0.98], P=0.20). The effect size revealed that
      the RBP4 level was higher in overweight or obese PCOS patients than weight
      matched controls (fixed effects MD (95% CI)=7.95, [5.96, 9.93], P<0.05). In the
      subgroup analysis by region, the RBP4 level was higher in PCOS patients in Asia
      than controls (random effects MD (95% CI)=0.85, [0.54, 1.15], P<0.05), but not in
      European PCOS patients compared with controls (random effects MD (95% CI)=0.34, [
      1.12, 1.80], P=0.65). This subgroup analysis also showed that nonobese PCOS
      patients have higher RBP4 levels than controls in Asia. Our meta-analysis results
      indicated that RBP4 might be a useful tool for identifying PCOS women. 

PMID- 25069672
TI  - Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase
      (PRKACA) gene in Japanese patients with several adrenal adenomas secreting
      cortisol [Rapid Communication].
AB  - Somatic mutations of the catalytic subunit of the cyclic AMP-dependent protein
      kinase (PRKACA) gene have recently been identified in about 35% of cortisol
      producing adenomas (CPAs), with the affected patients showing overt Cushing's
      syndrome. Since we recently reported higher prevalence of mutations of the KCNJ5
      gene and associations with autonomous cortisol secretion in Japanese aldosterone
      producing adenomas than in Western countries, there might be different features
      of CPAs between Japan and the West. We therefore investigated mutations of the
      PRKACA gene in Japanese patients with several adrenal tumors secreting cortisol,
      including overt Cushing's syndrome, subclinical Cushing's syndrome, and
      aldosterone-producing adenomas (APAs) co-secreting cortisol operated on at Gunma
      University Hospital. Of the 13 patients with CPA who showed overt Cushing's
      syndrome, 3 (23%) had recurrent somatic mutations of the PRKACA gene, p.L206R
      (c.617 T>G), and there were no mutations in subclinical Cushing's syndrome. Among
      33 APAs, 24 had somatic mutations of the KCNJ5 gene, either G151R or L168R, 11
      (33%) had autonomous cortisol secretion, but there were no mutations of the
      PRKACA gene. We established a PCR-restriction fragment length polymorphism assay
      and revealed that the mutated allele was expressed at a similar level to the wild
      type allele. These findings demonstrated that 1) the prevalence of Japanese
      patients with CPA who showed overt Cushing's syndrome and whose somatic mutations
      in the PRKACA gene was similar to that in Western countries, 2) the mutation
      might be specific for CPAs causing overt Cushing's syndrome, and 3) the mutant
      PRKACA allele was expressed appropriately in CPAs. 

PMID- 25069673
TI  - Likelihood ratio-based integrated personal risk assessment of type 2 diabetes.
AB  - To facilitate personalized health care for multifactorial diseases, risks of
      genetic and clinical/environmental factors should be assessed together for each
      individual in an integrated fashion. This approach is possible with the
      likelihood ratio (LR)-based risk assessment system, as this system can
      incorporate manifold tests. We examined the usefulness of this system for
      assessing type 2 diabetes (T2D). Our system employed 29 genetic susceptibility
      variants, body mass index (BMI), and hypertension as risk factors whose LRs can
      be estimated from openly available T2D association data for the Japanese
      population. The pretest probability was set at a sex- and age-appropriate
      population average of diabetes prevalence. The classification performance of our
      LR-based risk assessment was compared to that of a non-invasive screening test
      for diabetes called TOPICS (with score based on age, sex, family history,
      smoking, BMI, and hypertension) using receiver operating characteristic analysis
      with a community cohort (n = 1263). The area under the receiver operating
      characteristic curve (AUC) for the LR-based assessment and TOPICS was 0.707 (95%
      CI 0.665-0.750) and 0.719 (0.675-0.762), respectively. These AUCs were much
      higher than that of a genetic risk score constructed using the same genetic
      susceptibility variants, 0.624 (0.574-0.674). The use of ethnically matched LRs
      is necessary for proper personal risk assessment. In conclusion, although LR
      based integrated risk assessment for T2D still requires additional tests that
      evaluate other factors, such as risks involved in missing heritability, our
      results indicate the potential usability of LR-based assessment system and stress
      the importance of stratified epidemiological investigations in personalized
      medicine. 

PMID- 25069674
TI  - When reduction strategies are put in place and mental health consumers are still
      secluded: an analysis of clinical and sociodemographic characteristics.
AB  - Internationally, seclusion practices continue to be the subject of intense
      clinical health service and academic scrutiny. Despite extensive efforts to
      reduce and eliminate this controversial practice, seclusion remains a clinical
      intervention widely used in contemporary mental health service settings. Early
      identification of people who are at risk for seclusion and the timely application
      of alternative evidence-based interventions are critical for reducing incidents
      of seclusion in real-world practice settings. This retrospective study aimed to
      determine the relationship between sociodemographic and clinical characteristics,
      and the use of seclusion for those mental health consumers for whom evidence
      based seclusion-reduction initiatives had little impact. A 12-month centred
      moving average was fitted to seclusion data from a psychiatric inpatient unit
      over 2 years to determine stabilization in seclusion reduction. The number of
      consumers admitted was calculated from the point of stabilization for 1 year (n =
      469). In this cohort, univariate analysis sought to compare the characteristics
      of those who were secluded and those who were not. A multivariate logistic
      regression model was undertaken to associate future seclusion based on
      significant independent variables. Of those people admitted, 88 (19%) were
      secluded. The majority of seclusions occurred in the first 5 days (70/88, 79%).
      Multivariate logistic regression indicated that three variables maintained their
      independent associative risk of seclusion: (i) age less than 35 years; (ii)
      assessment of risk of violence to others; and (iii) a history of seclusion. The
      implications of these findings for nursing practice are discussed. 

PMID- 25069675
TI  - A new method to measure higher visual functions in an immersive environment.
AB  - BACKGROUND: Higher visual functions can be defined as cognitive processes
      responsible for object recognition, color and shape perception, and motion
      detection. People with impaired higher visual functions after unilateral brain
      lesion are often tested with paper pencil tests, but such tests do not assess the
      degree of interaction between the healthy brain hemisphere and the impaired one.
      Hence, visual functions are not tested separately in the contralesional and
      ipsilesional visual hemifields. METHODS: A new measurement setup, that involves
      real-time comparisons of shape and size of objects, orientation of lines, speed
      and direction of moving patterns, in the right or left visual hemifield, has been
      developed. The setup was implemented in an immersive environment like a
      hemisphere to take into account the effects of peripheral and central vision, and
      eventual visual field losses. Due to the non-flat screen of the hemisphere, a
      distortion algorithm was needed to adapt the projected images to the surface.
      Several approaches were studied and, based on a comparison between projected
      images and original ones, the best one was used for the implementation of the
      test. Fifty-seven healthy volunteers were then tested in a pilot study. A
      Satisfaction Questionnaire was used to assess the usability of the new
      measurement setup. RESULTS: The results of the distortion algorithm showed a
      structural similarity between the warped images and the original ones higher than
      97%. The results of the pilot study showed an accuracy in comparing images in the
      two visual hemifields of 0.18 visual degrees and 0.19 visual degrees for size and
      shape discrimination, respectively, 2.56 degrees  for line orientation, 0.33
      visual degrees/s for speed perception and 7.41 degrees  for recognition of motion
      direction. The outcome of the Satisfaction Questionnaire showed a high acceptance
      of the battery by the participants. CONCLUSIONS: A new method to measure higher
      visual functions in an immersive environment was presented. The study focused on
      the usability of the developed battery rather than the performance at the visual
      tasks. A battery of five subtasks to study the perception of size, shape,
      orientation, speed and motion direction was developed. The test setup is now
      ready to be tested in neurological patients.

PMID- 25069676
TI  - A bone metastases model of anaplastic thyroid carcinoma in athymic nude mice.
AB  - AIM: Anaplastic thyroid carcinoma (ATC), an aggressive form of thyroid cancer,
      represents less than 2% of all thyroid cancers. The survival of patients with ATC
      remains low especially when accompanied with bone metastasis. This study aims to
      establish a reproducible animal model of bone metastasis of ATC which may be
      useful for further research on novel treatment strategy. METHODS: Eight 6-8 week
      old female athymic nude mice were randomly selected. ATC cell line ARO cells were
      injected into the left ventricular cavity of each mouse respectively. Each mouse
      was imaged using a dedicated small-animal PET/CT scanner after successful
      injection of [(18)F]-FDG under deep anesthesia. Pathological examination was
      carried out to confirm the bone metastases of ATC. RESULTS: Histopathology
      established ATC bone metastases in five nude mice's tibia. Similarly, PET image
      displayed significantly increased radioactivity (P<0.01) in the established bone
      metastasis compared with the control normal tibia. CONCLUSIONS: Both micro-PET/CT
      and histomorphometric measurement confirmed the bone metastases model of ATC in
      nude mice by left ventricular cavity injection of ARO cell line. The bone
      metastases model of ATC will thus facilitate the understanding of its
      pathogenesis and aid in the development of novel therapies.

PMID- 25069677
TI  - Does the tympanic membrane have a natural opening? The historical saga of the
      foramen of Rivinus.
AB  - OBJECTIVES: From the end of the 17th century until well into the 20th century,
      the question of whether the tympanic membrane possesses a natural opening or not
      in its normal state has been the subject of much controversy. The aim of this
      study was to go back to the original documents describing this tympanic foramen,
      and to follow through the centuries the various controversies and discussions
      surrounding the presence or not of this foramen. DATA SOURCES: Selected
      otological textbooks and articles from the end of the 17th century until the
      second part of the 20th century. REVIEW METHOD: Historical. RESULTS: This study
      demonstrates the tenacity of the human brain in its regular review of questions
      that seem to have been answered, even when universal acceptation of said answer
      is almost present. The controversy around the foramen of Rivinus spanned nearly
      300 years, until the mid-20th century. CONCLUSIONS: The introduction of the
      regular use of an ear microscope to practice otoscopy gave the definitive answer:
      the tympanic membrane does not have a natural opening in its normal state. LEVEL
      OF EVIDENCE: NA.

PMID- 25069678
TI  - Exploration of potential EGFR inhibitors: a combination of pharmacophore-based
      virtual screening, atom-based 3D-QSAR and molecular docking analysis.
AB  - Epidermal growth factor receptor (EGFR) protein tyrosine kinases are over
      expressed in several human cancers and considered as a promising target for
      developing novel anticancer drugs. In this study, the ligand-based pharmacophore
      mapping and atom-based 3D-QSAR approach was carried out on a series of 40 novel
      pyrrolo[3, 2-d]pyrimidine derivatives acting as EGFR inhibitors. The best
      pharmacophore hypothesis AAADRR.295 was selected and an atom-based 3D-QSAR model
      was generated by applying partial least-squares algorithm. The developed model
      was validated and used as a 3D query in sequential virtual screening study to
      filter five chemical databases. The obtained compounds were further filtered
      according to Lipinski rule of five and fitness score. Subsequently, a multistep
      molecular docking study was employed on the retrieved hits and finally, 12
      compounds were prioritized as potential leads against EGFR, which exhibited high
      docking scores, correlated binding mode to experimentally proven compounds and
      constructive drug-like properties. The results of this study provide detailed
      structural insights and emphasize the important binding features of these
      compounds, which may assists in the design and development of novel EGFR
      inhibitors. 

PMID- 25069679
TI  - MicroRNA-21 coordinates human multipotent cardiovascular progenitors therapeutic
      potential.
AB  - Published clinical trials in patients with ischemic diseases show limited benefit
      of adult stem cell-based therapy, likely due to their restricted plasticity and
      commitment toward vascular cell lineage. We aim to uncover the potent
      regenerative ability of MesP1/stage-specific embryonic antigen 1 (SSEA-1)
      expressing cardiovascular progenitors enriched from human embryonic stem cells
      (hESCs). Injection of only 10(4) hESC-derived SSEA-1(+) /MesP1(+) cells, or their
      progeny obtained after treatment with VEGF-A or PDGF-BB, was effective enough to
      enhance postischemic revascularization in immunodeficient mice with critical limb
      ischemia (CLI). However, the rate of incorporation of hESC-derived SSEA-1(+)
      /MesP1(+) cells and their derivatives in ischemic tissues was modest.
      Alternatively, these cells possessed a unique miR-21 signature that inhibited
      phosphotase and tensin homolog (PTEN) thereby activating HIF-1alpha and the
      systemic release of VEGF-A. Targeting miR-21 limited cell survival and inhibited
      their proangiogenic capacities both in the Matrigel model and in mice with CLI.
      We next assessed the impact of mR-21 in adult angiogenesis-promoting cells. We
      observed an impaired postischemic angiogenesis in miR-21-deficient mice. Notably,
      miR-21 was highly expressed in circulating and infiltrated monocytes where it
      targeted PTEN/HIF-1alpha/VEGF-A signaling and cell survival. As a result, miR-21
      deficient mice displayed an impaired number of infiltrated monocytes and a
      defective angiogenic phenotype that could be partially restored by
      retransplantation of bone marrow-derived cells from wild-type littermates. hESC
      derived SSEA-1(+) /MesP1(+) cells progenitor cells are powerful key integrators
      of therapeutic angiogenesis in ischemic milieu and miR-21 is instrumental in this
      process as well as in the orchestration of the biological activity of adult
      angiogenesis-promoting cells.

PMID- 25069681
TI  - Formation of chiral nematic films from cellulose nanocrystal suspensions is a two
      stage process.
AB  - The evaporation of aqueous suspensions of cellulose nanocrystals (CNCs) gives
      iridescent chiral nematic films with reflection colors at visible wavelengths. A
      key problem is controlling the chiral nematic pitch, P, and hence the reflection
      colors of CNC films. By adding D-(+)-glucose to the suspension, we show that the
      change in P during evaporation occurs in two distinct stages. The first stage is
      the decrease in P as the concentration of CNC in the chiral nematic suspension
      increases due to evaporation; the addition of glucose causes a decrease in P at
      this stage. In a second stage, a concentration of CNC is reached where the
      formation of ordered gels and glasses prevents further major changes in P. The
      addition of glucose lowers the CNC concentration at which this occurs, leading to
      an increase in P and hence an overall shift to the red end of the spectrum in the
      final film.

PMID- 25069680
TI  - Effect of the PTEN gene on adhesion, invasion and metastasis of osteosarcoma
      cells.
AB  - The phosphatase and tensin homolog (PTEN) gene, an important tumor-suppressor
      gene, has been demonstrated to have the potential for inhibiting proliferation,
      migration and invasion in various types of cancer cells. The aim of the present
      study was to investigate the effect of PTEN expression on osteosarcoma (OS)
      cells. The wild-type PTEN plasmid was transfected into OS U2-OS cells. The
      effects of PTEN on the adhesion, migration and invasion of U2-OS cells were
      evaluated by cell adhesion analysis, in vitro scratch and Transwell assays,
      respectively. The levels of MMP-2 and MMP-9, and focal adhesion kinase (FAK)
      protein regulated by PTEN were detected via western blot analysis. Meanwhile, the
      level of intracellular FAK phosphorylation was observed. The results from the
      present study showed that overexpression of PTEN transcription and protein were
      observed in U2-OS cells following PTEN transfection. Furthermore, the migration,
      invasion and adhesion capabilities of the cells with PTEN transfection were
      significantly decreased compared to these capacities in the cells without PTEN.
      Meanwhile, it was shown that there was downregulation of MMP-9, FAK and p-FAK
      concomitant with the elevation of the intracellular PTEN level. It is therefore
      evident that the upregulation of PTEN may attenuate the adhesion, migration and
      invasion capabilities of OS cells. The mechanisms of the effects of PTEN on OS
      cells may be correlated with a reduction in the related genes by PTEN regulation.

PMID- 25069682
TI  - The efficacy of restaging endobronchial ultrasound in patients with non-small
      cell lung cancer after preoperative therapy.
AB  - BACKGROUND: Patient selection for surgery after neoadjuvant therapy for locally
      advanced non-small cell lung cancer depends on accurate restaging of mediastinal
      (N2) lymph nodes. Our objective is to assess the accuracy of endobronchial
      ultrasound (EBUS) for restaging N2 lymph nodes after neoadjuvant therapy.
      METHODS: This is a retrospective review of patients with non-small cell lung
      cancer who underwent staging with repeat computed tomography and positron
      emission tomography and had restaging EBUS for sampling of N2 lymph nodes.
      Endobronchial ultrasound was performed for suspicious nodes in stations 2R, 2L,
      4R, 4L, and 7. Selected patients who were N2-negative underwent thoracotomy with
      complete thoracic lymphadenectomy. RESULTS: There were 32 patients with N2
      disease who underwent preoperative chemotherapy or radiotherapy, or both, and
      subsequently had restaging EBUS. There were 3 patients who had recalcitrant N2
      nodal disease detected by EBUS. There were 5 patients with pulmonary function or
      comorbidities that were prohibitive for surgery. Of the remaining 24 patients
      with negative EBUS, 3 underwent mediastinoscopy and 2 had recalcitrant N2
      disease. The remaining 22 patients underwent thoracotomy. Recalcitrant N2 disease
      was noted in 1 patient at thoracotomy in the EBUS-assessable nodal stations. Thus
      EBUS was falsely negative in 3 patients. The sensitivity and negative predictive
      value of restaging EBUS were 50% and 88%, respectively. CONCLUSIONS: Restaging
      EBUS is relatively accurate at predicting the absence of metastatic disease in N2
      mediastinal lymph node in patients who underwent neoadjuvant therapy for non
      small cell lung cancer.

PMID- 25069684
TI  - Blunt cardiac trauma: a review of the current knowledge and management.
AB  - Blunt cardiac injuries are highly lethal. A review of the world's English
      literature on the topic reveals a lack of Level 1 Evidence and few cohesive
      guidelines for the management of these patients. An online database query was
      performed using the PubMed medical database. All relevant articles from the past
      20 years were reviewed. Conclusions are presented with their corresponding Levels
      of Evidence.

PMID- 25069683
TI  - Surgical lung biopsy in adult respiratory distress syndrome: a meta-analysis.
AB  - BACKGROUND: Adult respiratory distress syndrome (ARDS) has a high mortality rate
      and consumes considerable health care resources. It is not clear whether
      specimens obtained from open lung biopsy (OLB) in ARDS provide a specific
      diagnosis, alter therapy, or affect outcome. This meta-analysis attempts to
      determine whether OLB is safe, provides a specific diagnosis, changes therapy, or
      affects survival. METHODS: A computerized search was performed of Medline and
      PubMed from January 1988 to December 2012 of English language studies of acute
      respiratory failure and diffuse pulmonary infiltrates that evaluated OLB in
      primarily adult mechanically ventilated patients. Of 194 abstracts retrieved, 64
      articles were reviewed; 130 articles were excluded because they did not evaluate
      OLB. After applying the selection criteria, 24 articles were included. RESULTS:
      OLB in ARDS provided a specific diagnosis in 84% of patients and altered
      management in 73%. Hospital mortality was 43%. The complication rate for OLB in
      ARDS was 22%, but death from OLB was rare. CONCLUSIONS: OLB in ARDS is a
      potentially productive procedure that provides a specific diagnosis and leads to
      a change in management in high proportions of patients. ARDS has a high mortality
      rate, which OLB does not appear to increase. Owing to a lack of randomized
      controlled trials, a survival advantage of OLB in ARDS could not be demonstrated.

PMID- 25069685
TI  - De novo aortic regurgitation after continuous-flow left ventricular assist device
      implantation.
AB  - BACKGROUND: Significant aortic regurgitation (AR) after continuous-flow left
      ventricular assist device (cf-LVAD) placement affects device performance and
      patient outcomes. This study examined the development of AR and long-term results
      after implantation of cf-LVADs. METHODS: The study included all patients with no
      or less than mild AR who underwent HeartMate II (58 [62%]; Thoratec Corp,
      Pleasanton, CA) or HeartWare (35 [38%]; HeartWare International, Framingham, MA)
      implantation at our institute from July 2006 to July 2012. Serial echocardiograms
      were obtained preoperatively, at 1, 3 and 6 months postoperatively, and then at a
      minimum of 4-month intervals in patients with longer-term support. Kaplan-Meier
      estimates for freedom from moderate or greater AR were generated. Logistic
      regression analysis was used to define independent predictors of AR after cf-LVAD
      implantation. RESULTS: Median duration of LVAD support was 527 days (25(th),
      75(th): 289, 907; range, 60 to 2,433 days). Mild AR developed in 48 patients
      (51.6%) over a median duration of 126 days, with progression to moderate AR in 13
      (14%) over 493 days and to severe AR in 2 (2.1%) over 1,231 days. The incidence
      of mild or greater AR was 43.1% in HeartMate II vs 65.7% in HeartWare recipients
      (p = 0.035). Overall freedom from moderate or greater AR was 94.7% +/- 2.6% at 1
      year, 86.9% +/- 4.5% at 2 years, 82.8% +/- 5.9% at 3 years, and 31% +/- 16.9% at
      4 years. Independent predictors of AR were duration of support (odds ratio,
      1.002; 95% confidence interval, 1.000 to 1.004; p = 0.017) and a persistently
      closed aortic valve (odds ratio, 0.193; 95% confidence interval, 0.097 to 0.382;
      p < 0.001). CONCLUSIONS: AR is associated with longer cf-LVAD support duration
      and persistent aortic valve closure. Incidence of moderate or greater AR after cf
      LVAD implantation increases significantly after 3 years. The clinical
      implications of these data may warrant consideration of prophylactic aortic valve
      replacement at the time of cf-LVAD implantation, particularly with expected
      longer duration of support and in patients with preexisting AR that is more than
      mild.

PMID- 25069686
TI  - Surgeon and center volume influence on outcomes after arterial switch operation:
      analysis of the STS Congenital Heart Surgery Database.
AB  - BACKGROUND: The relative impact of center volume and of surgeon volume on early
      outcomes after the arterial switch operation (ASO) is incompletely understood.
      METHODS: Neonates in the Society of Thoracic Surgeons Congenital Heart Surgery
      Database (2005-2012) undergoing ASO for transposition of the great arteries were
      included in the analysis. Multivariable logistic regression with adjustment for
      patient factors and ventricular septal defect closure was used to evaluate
      relationships between annual center and surgeon volume and a composite end point
      (in-hospital mortality or major complications). RESULTS: The study included 2,357
      patients (84 centers, 155 surgeons). Median annual ASO center volume was 4
      (range, 1 to 18). Median annual surgeon volume was 2 (range, 0.1 to 11). In
      hospital mortality was 3.4%; 14.7% had major morbidity and 15.5% met the
      composite end point. Analyzed individually, lower center and surgeon volumes were
      each associated with the composite end point (odds ratios for centers with 2
      versus 10 cases/y, 1.92; 95% confidence interval, 1.23 to 2.99); odds ratios for
      surgeons with 1 versus 6 cases/y, 2.16; 95% confidence interval, 1.42 to 3.26).
      When analyzed together, the addition of surgeon volume to the center volume
      models attenuated but did not completely mitigate the association of center
      volume with outcome (relative attenuation of odds ratio = 31%). Addition of
      center volume to surgeon volume models attenuated the association of surgeon
      volume with outcome to a lesser degree (relative attenuation of odds ratio =
      11%). CONCLUSIONS: Center and surgeon volume each influence early outcomes after
      ASO; however, surgeon volume appears to play a more prominent role. Surgeon and
      center ASO volume should be considered in the context of initiatives to improve
      outcomes from ASO for transposition of the great arteries.

PMID- 25069687
TI  - Long-term outcome after resection of non-small cell lung cancer invading the
      thoracic inlet.
AB  - BACKGROUND: The aim of this study was to update our previous experience and
      describe long-term results after resection of non-small-cell lung cancer (NSCLC)
      invading the thoracic inlet. METHODS: Patients from a single center undergoing
      resection of NSCLC invading the thoracic inlet were reviewed with data retrieved
      retrospectively from their charts. RESULTS: Sixty-five consecutive patients with
      a median age of 61 (32-76) years underwent resection of NSCLC invading the
      thoracic inlet from 1991 to 2011. Tumor location was divided into 5 anatomic
      zones from anterior to posterior. Fifty-two (80%) patients had induction therapy,
      mostly with 2 cycles of cisplatin-etoposide and 45 Gy of concurrent irradiation.
      All patients underwent at least first rib resection. Lobectomy was performed in
      60 patients (92%). Twenty-four patients (37%) had vertebral resection. Arterial
      resections were performed in 7 patients (11%). Postoperative morbidity and
      mortality were 46% and 6%, respectively. Pathologic response to induction was
      complete (pCR) (n = 19) or nearly complete (pNR) (n = 12) in 31 patients (48%).
      Adjuvant treatment was administered in 14 (25%) patients. After a median follow
      up of 20 (0-193) months, 34 patients are alive without recurrence. The overall 5
      year survival reached 69%. Univariate analysis identified site of tumor within
      the thoracic inlet (p = 0.050), response to induction (p = 0.004), and presence
      of adjuvant treatment (p = 0.028) as survival predictors. CONCLUSIONS: Survival
      after resection of NSCLC invading the thoracic inlet in highly selected patients
      reached 69% at 5 years. Tumor location within the thoracic inlet, pathologic
      response to induction therapy, and adjuvant treatments were significant survival
      predictors.

PMID- 25069688
TI  - Combined heart and liver transplantation can be safely performed with excellent
      short- and long-term results.
AB  - BACKGROUND: Heart transplant has become the gold standard therapy for end-stage
      heart failure. Short- and long-term outcomes after orthotopic heart transplant
      have been excellent. Many patients with heart failure manifest hepatic failure as
      a result of a chronically elevated central venous pressure. Concomitant hepatic
      failure has been a contraindication to heart transplant in most centers. A few
      select institutions are currently performing combined heart-liver transplantation
      to treat dual organ failure. The outcomes after dual organ transplant are largely
      unknown, with limited data from a few select centers. We undertook this study to
      analyze our large experience with combined heart-liver transplant and determine
      the short-term and long-term outcomes associated with this procedure. METHODS: We
      have performed 1,050 heart transplants at our center to date. Of these patients,
      26 underwent combined heart and liver transplant (largest single-center
      experience). We reviewed demographic, perioperative, and short- and long-term
      outcomes after this combined procedure. RESULTS: All 26 patients underwent
      successful dual organ transplant, without any episodes of primary graft
      dysfunction. Average length of intensive care unit stay was 10 +/- 5 days, and
      average hospital stay was 25 +/- 11 days. Kaplan-Meier analysis demonstrated
      excellent short-term survival (1 year, 87% +/- 7%) and long-term survival (5
      years, 83% +/- 8%). Interestingly, only 3 patients (11%) demonstrated any
      evidence of rejection long-term by myocardial biopsy, suggesting that concomitant
      hepatic transplantation may provide immunologic protection for the cardiac
      allograft. CONCLUSIONS: We present the largest single-center series of combined
      heart and liver transplant. This dual organ strategy is highly feasible, with
      excellent long-term survival. Concomitant liver transplant may confer immunologic
      protection for the cardiac allograft.

PMID- 25069689
TI  - Does renal dysfunction and method of bridging support influence heart transplant
      graft survival?
AB  - BACKGROUND: Renal insufficiency is common in status 1B patients supported with
      inotropes or a continuous flow left ventricular device (CF-LVAD) as a bridge to
      heart transplantation. We evaluated the association of renal function and
      inotrope versus CF-LVAD support on posttransplant graft survival in status 1B
      patients. METHODS: The Scientific Registry for Transplant Recipients database was
      analyzed for posttransplant survival in status 1B patients bridged with inotropes
      or CF-LVAD who underwent transplantation between 2003 and 2012. Pretransplant
      renal function was measured by estimating glomerular filtration rate (GFR) and
      was stratified as less than 45 mL . min(-1) . 1.73 m(-2), 45 to 59, and 60 or
      greater. Univariate Kaplan-Meier and multivariate Cox regression models were used
      to evaluate the main effects of GFR strata and inotropes versus CF-LVAD, and the
      interaction effect of GFR strata by CF-LVAD, on graft survival. RESULTS: This
      study included 4,158 status 1B patients (74% male, aged 53 +/- 12 years). Of
      those, 659 patients had a CF-LVAD (HeartMate-II [Thoratec, Pleasanton, CA], n =
      638; HVAD [HeartWare, Framingham, MA], n = 21), and 3,530 were receiving
      inotropes (31 CF-LVAD patients were also receiving inotropes). Kaplan-Meier
      analyses demonstrated reduced graft survival (p = 0.022) in patients with
      pretransplant GFR less than 45 versus GFR 45 to 59 (p = 0.062) and versus GFR 60
      or greater (p = 0.007), and no effect of inotrope versus CF-LVAD support on graft
      survival (p = 0.402). Multivariate analysis demonstrated that, after adjusting
      for the main effects of GFR stratum, CF-LVAD, and inotropes, status 1B patients
      bridged with a CF-LVAD and GFR in the lowest stratum had reduced graft survival
      (interaction effect p = 0.040). CONCLUSIONS: Pretransplant renal insufficiency
      was associated with reduced posttransplant graft survival in status 1B patients.
      This risk is increased for patients bridged with a CF-LVAD (versus inotropes) who
      have GFR in the lowest stratum.

PMID- 25069690
TI  - Local injection of substance P increases bony formation during mandibular
      distraction osteogenesis in rats.
AB  - Substance P is a neuropeptide that is distributed in those sensory nerve fibres
      that innervate the medullary tissues of bone. It is a potent accelerator of
      proliferation and differentiation of osteoblasts in vitro. However, its capacity
      for promoting repair of mandibular defects is not known. We have investigated the
      osteogenic effects of local injections of substance P during mandibular
      distraction osteogenesis in rats. Twenty Sprague-Dawley rats were randomly
      assigned to 2 groups (n = 10 in each): substance P 10(-7) mmol/l in normal saline
      0.2ml was injected into the experimental group, and saline alone into the
      controls. The mandibular distraction rate was 0.2mm every 12hours for 10 days.
      Daily injections of substance P or saline were given during the distraction
      period. Regeneration of bone was assessed quantitatively on days 15 and 29 using
      microcomputed tomography (microCT), and histological analysis. The rate of bony
      union in the group treated with substance P was significantly higher than that in
      the saline alone group on day 29 (p=0.001) The microCT images and quantitation
      showed more callus and more mature cortical bone when substance P was given than
      with control. Histological examination showed that cartilaginous tissues had
      formed in the middle of the distraction gaps in both groups. Bony bridges were
      seen only in the substance P group at the final time point (day 29). Injection of
      substance P into the gap of a rat mandible during mandibular distraction improved
      formation of good-quality bone and accelerated bony union. 

PMID- 25069693
TI  - Discovery-based protein expression profiling identifies distinct subgroups and
      pathways in leiomyosarcomas.
AB  - Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A
      substantial portion of these tumors exhibits complex karyotypes and lack
      characterized chromosomal aberrations. Owing to such properties, both
      histopathologic and molecular classification of these tumors has been a
      significant challenge. This study examines the protein expression of a large
      number of human STS, including subtype heterogeneity, using two-dimensional gel
      proteomics. In addition, detailed proteome profiles of a subset of pleomorphic
      STS specimens using an in-depth mass-spectrometry approach identified subgroups
      within the leiomyosarcomas with distinct protein expression patterns. Pathways
      analysis indicates that key biologic nodes like apoptosis, cytoskeleton
      remodeling, and telomere regulation are differentially regulated among these
      subgroups. Finally, investigating the similarities between protein expression of
      leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar
      protein expression profiles for these tumors, in comparison with pleomorphic
      leiomyosarcomas. IMPLICATIONS: These results suggest that UPS tumors share a
      similar lineage as leiomyosarcomas and are likely to originate from different
      stages of differentiation from mesenchymal stem cells to smooth muscle cells.

PMID- 25069691
TI  - Stimulating antitumor immunity with nanoparticles.
AB  - A variety of strategies, have been applied to cancer treatment and the most
      recent one to become prominent is immunotherapy. This interest has been fostered
      by the demonstration that the immune system does recognize and often eliminate
      small tumors but tumors that become clinical problems block antitumor immune
      responses with immunosuppression orchestrated by the tumor cells. Methods to
      reverse this tumor-mediated immunosuppression will improve cancer immunotherapy
      outcomes. The immunostimulatory potential of nanoparticles (NPs), holds promise
      for cancer treatment. Phagocytes of various types are an important component of
      both immunosuppression and immunostimulation and phagocytes actively take up NPs
      of various sorts, so NPs are a natural system to manipulate these key immune
      regulatory cells. NPs can be engineered with multiple useful therapeutic
      features, such as various payloads such as antigens and/or immunomodulatory
      agents including cytokines, ligands for immunostimulatory receptors or
      antagonists for immunosuppressive receptors. As more is learned about how tumors
      suppress antitumor immune responses the payload options expand further. Here we
      review multiple approaches of NP-based cancer therapies to modify the tumor
      microenvironment and stimulate innate and adaptive immune systems to obtain
      effective antitumor immune responses.

PMID- 25069695
TI  - Direct observation of the formation and destruction of the inverted continuous
      oil phase in the micro-outlet region achieved by the confined diluted O/W
      emulsion stream.
AB  - We demonstrate a direct observation of the oil-in-water (O/W) emulsion droplets
      in a confined point contact geometry, to shed new light on the mechanism of the
      interaction between emulsion and solid surfaces under confinement. Significantly,
      the behavior of droplets at the outlet of the contact area is highlighted. The
      interference technique offers capabilities to distinguish different phase of
      liquid based on the divisive refractive indices. A continuous oil phase can be
      initially obtained surrounding the contact area, at both the inlet and outlet, as
      a result of the confinement-induced phase inversion, which has been recognized as
      the efficient reservoir to the contact. However, in the outlet region, such
      reservoir is observed to be readily destroyed by the backflow of the diluted bulk
      emulsion, resulting in a notable coexistence of both the O/W and W/O phases in
      several distinguishing microscopic zones adjacent to each other. This suggests
      that the breakup of the reservoir may underlie the limited absorption and
      lubricity of diluted O/W emulsion systems. 

PMID- 25069694
TI  - Sun exposure and melanoma survival: a GEM study.
AB  - BACKGROUND: We previously reported a significant association between higher UV
      radiation exposure before diagnosis and greater survival with melanoma in a
      population-based study in Connecticut. We sought to evaluate the hypothesis that
      sun exposure before diagnosis was associated with greater survival in a larger,
      international population-based study with more detailed exposure information.
      METHODS: We conducted a multicenter, international population-based study in four
      countries-Australia, Italy, Canada, and the United States-with 3,578 cases of
      melanoma with an average of 7.4 years of follow-up. Measures of sun exposure
      included sunburn, intermittent exposure, hours of holiday sun exposure, hours of
      water-related outdoor activities, ambient ultraviolet B (280-320 nm) dose,
      histologic solar elastosis, and season of diagnosis. RESULTS: Results were not
      strongly supportive of the earlier hypothesis. Having had any sunburn in 1 year
      within 10 years of diagnosis was inversely associated with survival; solar
      elastosis-a measure of lifetime cumulative exposure-was not. In addition, none of
      the intermittent exposure measures-water-related activities and sunny holidays
      were associated with melanoma-specific survival. Estimated ambient UVB dose was
      not associated with survival. CONCLUSION: Although there was an apparent
      protective effect of sunburns within 10 years of diagnosis, there was only weak
      evidence in this large, international, population-based study of melanoma that
      sun exposure before diagnosis is associated with greater melanoma-specific
      survival. IMPACT: This study adds to the evidence that sun exposure before
      melanoma diagnosis has little effect on survival with melanoma.

PMID- 25069696
TI  - Biomechanical comparison of canine fascia lata and thoracolumbar fascia: an in
      vitro evaluation of replacement tissues for body wall reconstruction.
AB  - OBJECTIVES: To compare the suitability of thoracolumbar fascia (TLF) and fascia
      lata (FL) for body wall defect repair in dogs, by examining their biomechanical
      properties and useable surface area. STUDY DESIGN: Experimental. ANIMALS: Dogs (n
      = 8). METHODS: Fresh TLF and FL grafts were obtained, surface area was calculated
      before testing to failure in 2 different modes: tensile testing and resistance to
      suture pullout, in 2 perpendicular orientations. RESULTS: Useable TLF surface
      area was significantly greater than for FL. Maximum load, energy to break, and
      elastic modulus of FL was significantly greater than that of TLF in tensile
      testing, but no apparent difference in the ultimate stress or strain was
      identified. There was no overall difference in suture pullout load between TLF
      and FL. During tensile testing, tissue orientation had a significant influence on
      ultimate load, stress, and elastic modulus for both tissue types, with strain and
      energy to break only having significant effects for TLF and FL, respectively.
      CONCLUSIONS: The greater tensile strength and stiffness of FL compared to TLF was
      not reflected in its material properties, implying any difference was a
      consequence of greater thickness. Suture pullout was not significantly different
      between the 2 tissues, perhaps limiting the clinical significance of the tissue
      mechanics. Tissues were anisotropic with respect to mechanical properties, thus
      orientation may be an important factor.

PMID- 25069697
TI  - Daphnia longicephala neuropeptides: morphological description of crustacean
      cardioactive peptide (CCAP) and periviscerokinins in the Ctenodaphnia central
      nervous system.
AB  - The publication of the Daphnia genome has driven research in this ecologically
      relevant model organism in many directions. However, information on this
      organism's physiology and the relevant controlling factors is limited. In this
      regard, especially neuropeptides are important biochemical regulators that
      control a variety of cellular processes, which in combination influence
      physiological conditions and allow the adaptation of the internal physiological
      state to external conditions. Thus, neuropeptides are prime in understanding an
      organism's physiology. We here aimed to detect and describe the distribution of
      evolutionary conserved neuropeptides including the crustacean cardioactive
      peptide (CCAP) and peptides of the family periviscerokinins (PVKs) in the central
      nervous system and the periphery of the Daphnia longicephala head region. We were
      able to identify a large pair of CCAP immunoreactive cells within central nervous
      system. In addition, in the periphery we found CCAP immunoreactive cells in the
      epidermis of the head with processes indicating cuticular secretion. Furthermore,
      we were able to identify and describe a complex neuronal circuit of PVK
      neuropeptides in the central nervous system. The data obtained in this study will
      provide important background information for future investigations aiming to
      unravel the cellular, neuronal and physiological pathways in a highly adaptive
      organism such as Daphnia.

PMID- 25069699
TI  - Correction.

PMID- 25069698
TI  - Interferon regulatory factor (IRF) 3 is critical for the development of
      experimental autoimmune encephalomyelitis.
AB  - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal model of
      autoimmune inflammatory demyelination that is mediated by Th1 and Th17 cells. The
      transcription factor interferon regulatory factor 3 (IRF3) is activated by
      pathogen recognition receptors and induces interferon-beta production. METHODS:
      To determine the role of IRF3 in autoimmune inflammation, we immunised wild-type
      (WT) and irf3(-/-) mice to induce EAE. Splenocytes from WT and irf3(-/-) mice
      were also activated in vitro in Th17-polarising conditions. RESULTS: Clinical
      signs of disease were significantly lower in mice lacking IRF3, with reduced Th1
      and Th17 cells in the central nervous system. Peripheral T-cell responses were
      also diminished, including impaired proliferation and Th17 development in irf3(-/
      ) mice. Myelin-reactive CD4+ cells lacking IRF3 completely failed to transfer EAE
      in Th17-polarised models as did WT cells transferred into irf3(-/-) recipients.
      Furthermore, IRF3 deficiency in non-CD4+ cells conferred impairment of Th17
      development in antigen-activated cultures. CONCLUSION: These data show that IRF3
      plays a crucial role in development of Th17 responses and EAE and warrants
      investigation in human multiple sclerosis.

PMID- 25069700
TI  - Global DNA methylation as a possible biomarker for diabetic retinopathy.
AB  - BACKGROUND: We evaluated whether global levels of DNA methylation status were
      associated with retinopathy as well as providing a predictive role of DNA
      methylation in developing retinopathy in a case-control study of 168 patients
      with type 2 diabetes. METHODS: The 5-methylcytosine content was assessed by
      reversed-phase high-pressure liquid chromatography of peripheral blood leukocytes
      to determine an individual's global DNA methylation status in the two groups,
      either with or without retinopathy. RESULTS: The global DNA methylation levels
      were significantly higher in diabetic retinopathy patients compared with those in
      non-retinopathy patients (4.90 +/- 0.12 vs. 4.22 +/- 0.13, respectively; p =
      0.001). There was a significant increasing trend in global DNA methylation levels
      in terms of progressing retinopathy (without retinopathy, 4.22 +/- 0.13; non
      proliferative diabetic retinopathy, 4.62 +/- 0.17; proliferative diabetic
      retinopathy, 5.07 +/- 0.21) (p = 0.006). Additionally, global DNA methylation
      independent of retinopathy risk factors, which include dyslipidaemia,
      hypertension, hyperglycaemia and duration of diabetes, was a predictive factor
      for retinopathy (OR = 1.53, p = 0.015). CONCLUSIONS: Global DNA methylation is
      modulated during or possibly before the primary stage of diabetes. This
      observation verifies the metabolic memory effect of hyperglycaemia in early stage
      of an aetiological process that leads to type 2 diabetes and its associated
      complications.

PMID- 25069701
TI  - Glucocorticoids in myasthenia gravis - if, when, how, and how much?
AB  - Glucocorticoids (GC) are the most commonly used immune-directed therapy in
      myasthenia gravis (MG). However, to date, GC have not proven their effectiveness
      in the setting of a randomized clinical trial that complies with currently
      accepted standards. The rationale for the use of GC in MG is the autoimmune
      nature of the disease, which is supported by consistent positive results from
      retrospective studies. Well-defined recommendations for treatment of MG with GC
      are lacking and further hampered by inter- and intra-individual differences in
      the disease course and responses to GC treatment. Uncertainties concerning GC
      treatment in MG encompass the indication for treatment initiation, exact dosage,
      dose adjustment in specific conditions (e.g., pregnancy, thymectomy), mode of
      tapering, and surveillance of adverse events (AE). This review illustrates the
      mode of action of GC in the treatment for MG, presents the currently available
      data on GC treatment in MG, and attempts to translate the currently available
      information into clinical recommendations. 

PMID- 25069702
TI  - Synthesis, enzymatic resolution, and stereochemical characterization of
      isoparaconic acid derivatives: a combined experimental and theoretical
      investigation.
AB  - Enantiomerically enriched isoparaconic acid derivatives were obtained by kinetic
      enzymatic resolution. To explain the solvent dependence observed for their
      optical rotatory power a computational investigation of their chiroptical
      properties was performed.

PMID- 25069703
TI  - Cancer caregiving tasks and consequences and their associations with caregiver
      status and the caregiver's relationship to the patient: a survey.
AB  - BACKGROUND: Seriously ill patients often depend on their informal caregivers to
      help and support them through the disease course. This study investigated
      informal cancer caregivers' experiences of caregiving tasks and consequences and
      how caregiver status (primary vs. non-primary caregiver) and the caregiver's
      relationship to the patient (spouse/partner, etc.) are related to these
      experiences. METHODS: In a cross-sectional questionnaire study, randomly selected
      cancer patients with a range of diagnoses and disease stages were invited to pass
      on the 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN)
      to 1-3 of their caregivers. RESULTS: A total of 590 caregivers related to 415
      (55% of 752 eligible) cancer patients participated. Large proportions of
      caregivers experienced substantial caregiving workload, e.g., provision of
      psychological support (74%), as well as a range of negative consequences, most
      commonly stress (59%). Some caregivers experienced personal growth, but
      relatively large proportions did not. Caregiver status and the caregiver's
      relationship to the patient were associated with some caregiving aspects. Primary
      caregivers experienced the highest caregiving workload, and non-primary
      caregivers experienced most problems with getting time off from work.
      Spouses/partners and/or parents experienced the highest workload, most lack of
      time for social relations, most financial difficulties, and had the greatest need
      for seeing a psychologist. They furthermore experienced the highest degree of
      personal growth and had the smallest need for living a normal life while being a
      caregiver. Yet, regarding the majority of caregiving aspects, no associations
      with caregiver status or the caregiver's relationship to the patient were found.
      CONCLUSIONS: Overall, the findings confirm that cancer caregiving is burdensome.
      The primary and the closest caregivers seemed to take on most caregiving tasks,
      but, contrary to expectations, regarding the majority of caregiving consequences
      non-primary and more distant caregivers were affected to the same degree as the
      primary and closest caregivers. Initiatives and interventions to support not only
      the primary caregivers are therefore warranted.

PMID- 25069704
TI  - Predicting risk of upper gastrointestinal bleed and intracranial bleed with
      anticoagulants: cohort study to derive and validate the QBleed scores.
AB  - OBJECTIVE: To develop and validate risk algorithms (QBleed) for estimating the
      absolute risk of upper gastrointestinal and intracranial bleed for patients with
      and without anticoagulation aged 21-99 years in primary care. DESIGN: Open cohort
      study using routinely collected data from general practice linked to hospital
      episode statistics data and mortality data during the five year study period
      between 1 January 2008 and 1 October 2013. SETTING: 565 general practices in
      England contributing to the national QResearch database to develop the algorithm
      and 188 different QResearch practices to validate the algorithm. All 753 general
      practices had data linked to hospital episode statistics and mortality data at
      individual patient level. ENDPOINT: Gastrointestinal bleed and intracranial bleed
      recorded on either the linked mortality data or the linked hospital records.
      PARTICIPANTS: We studied 4.4 million patients in the derivation cohort with 16.4
      million person years of follow-up. During follow-up, 21,641 patients had an
      incident upper gastrointestinal bleed and 9040 had an intracranial bleed. For the
      validation cohort, we identified 1.4 million patients contributing over 4.9
      million person years of follow-up. During follow-up, 6600 patients had an
      incident gastrointestinal bleed and 2820 had an intracranial bleed. We excluded
      patients without a valid Townsend score for deprivation and those prescribed
      anticoagulants in the 180 days before study entry. RISK FACTORS: Candidate
      variables recorded on the general practice computer system before entry to the
      cohort, including personal variables (age, sex, Townsend deprivation score,
      ethnicity), lifestyle variables (smoking, alcohol intake), chronic diseases,
      prescribed drugs, clinical values (body mass index, systolic blood pressure), and
      laboratory test results (haemoglobin, platelets). We also included previous bleed
      recorded before entry to the study. RESULTS: The final QBleed algorithms
      incorporated 21 variables. When applied to the validation cohort, the algorithms
      in women explained 40% of the variation for upper gastrointestinal bleed and 58%
      for intracranial bleed. The corresponding D statistics were 1.67 and 2.42. The
      receiver operating curve statistic values were 0.77 and 0.86. The sensitivity
      values for the top 10th of men and women at highest risk were 38% and 51%,
      respectively. There were similar results for men. CONCLUSION: The QBleed
      algorithms provided valid measures of absolute risk of gastrointestinal and
      intracranial bleed in patients with and without anticoagulation as shown by the
      performance of the algorithms in a separate validation cohort. Further research
      is needed to evaluate the clinical outcomes and the cost effectiveness of using
      these algorithms in primary care.

PMID- 25069705
TI  - Reconsideration of the relevance of mild wedge or short vertebral height
      deformities across a broad age distribution.
AB  - Based on an evaluation of vertebral fracture prevalence on lateral radiographs
      across all age groups in a large cohort, mild or wedge-shaped vertebral body
      changes identified among adults should be managed as osteoporosis or at least
      considered as a risk factor for osteoporotic fracture, since they are rare among
      young subjects. INTRODUCTION: Radiographic assessment of vertebral fractures is
      limited by the inability to distinguish mild fractures from congenital mild wedge
      deformities or vertebrae of short vertebral height. We attempted to quantify the
      expected background prevalence of these deformities by measuring vertebral
      fracture prevalence across all age groups in a large hospital-based retrospective
      Chinese cohort. METHODS: We reviewed eligible lateral chest radiographs from
      patients admitted to Peking Union Medical College Hospital during 2011 using the
      Genant semiquantitative method for vertebral fracture assessment (T4-L2). We
      evaluated fracture prevalence among subjects by sex, 10-year age group, and
      fracture severity grades subjectively. We further analyzed characteristics of
      subjects with mild (grade I) fractures to estimate the relative contribution of
      congenital mild wedge deformities. RESULTS: A total of 10,720 subjects (5,396 men
      and 5,324 women) with lateral chest radiographs were evaluated. Subjects ranged
      in age from 0.5 to 97 years with a mean of 51.8 +/- 17.4 years (men 52.8 +/- 17.6
      years; women 50.8 +/- 17.2 years). When stratified by 10-year age groups, the
      prevalence of vertebral fractures was relatively low until about 40 years of age,
      after which prevalence increased for both genders. Fractures (13 fractures for 9
      males and 6 fractures for 5 females) seen in subjects younger than 40 years of
      age were almost exclusively mild grade fractures. No fractures were identified in
      subjects younger than 20 years of age. CONCLUSIONS: Mild or wedge-shaped
      vertebral body changes on lateral radiographs are rare among young subjects,
      indicating that when mild vertebral deformities are found among adults, they are
      likely to be the product of aging and not congenital variation. Clinically,
      therefore, mild vertebral body changes should be managed as osteoporosis or at
      least considered as a risk factor for osteoporotic fracture.

PMID- 25069706
TI  - A trabecular plate-like phenotype is overrepresented in Chinese-American versus
      Caucasian women.
AB  - This study used extreme phenotype selection to define two trabecular bone
      phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular
      plate-predominant phenotype is more common in Chinese-Americans while the rod
      predominant phenotype is more typical of Caucasians. The robustness of these
      phenotypic associations with respect to lifestyle factors suggests that this
      trait may have a genetic basis and that these phenotypes can be utilized in
      future genetic studies. INTRODUCTION: Compared to Caucasians, Chinese-Americans
      have more plate-like trabecular bone when measured by individual trabecula
      segmentation (ITS). These findings suggest a phenotypic difference between the
      races, which may be amenable to genetic analysis. We sought to identify a single
      ITS plate trait to pursue in genetic studies by conducting an extreme phenotype
      selection strategy to numerically define two distinct phenotypes-plate-like and
      rod-like-and determine whether the selected phenotypic associations were
      independent of lifestyle factors in order to conduct future genetic studies.
      METHODS: A previously described cohort of 146 Chinese-American and Caucasian
      women with high-resolution peripheral quantitative computed tomography imaging
      and ITS analyses were studied with logistic regression and receiver operator
      characteristic analyses. RESULTS: The tibial plate-to-rod (TPR) ratio was the
      best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio
      phenotypes were defined numerically: plate-like as a TPR ratio value in the
      highest quartile (>=1.336) and rod-like as a TPR ratio value in the lowest
      quartile (<=0.621). Women with a plate-like phenotype were 25.7 times more likely
      (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology.
      After controlling for constitutional and lifestyle covariates, women in the
      highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7
      568.0) to be Chinese-American. CONCLUSION: Using extreme phenotype selection, we
      defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait.
      The former phenotype is more common in Chinese-American women, while the latter
      is more typical of Caucasian women. The robustness of these phenotypic
      associations after controlling for differences in constitution and lifestyle
      suggest that the TPR ratio may have a genetic basis and that the extreme
      phenotypes defined in this analysis can be utilized for future studies.

PMID- 25069708
TI  - Azathioprine as a therapeutic alternative for refractory chronic urticaria.
AB  - BACKGROUND: Chronic urticaria (CU) affects up to 1% of the general population.
      Its impact on quality of life is immense, and patients might require multiple
      drugs to control symptoms. The main therapeutic challenge in the treatment of CU
      is to maintain symptomatic control while minimizing the use of
      glucocorticosteroids and their plethora of side effects. METHODS: Two patients
      with severe, refractory CU after treatment failure with various drugs, including
      high-dose cyclosporine, were administered azathioprine. RESULTS: In both
      patients, the treatment with azathioprine resulted in a significant clinical
      improvement, enabling steroid withdrawal. CONCLUSION: Azathioprine should be
      considered as a therapeutic option for chronic, steroid-dependent urticaria,
      refractory to other treatments.

PMID- 25069709
TI  - Decision aids for advance care planning: an overview of the state of the science.
AB  - Advance care planning honors patients' goals and preferences for future care by
      creating a plan for when illness or injury impedes the ability to think or
      communicate about health decisions. Fewer than 50% of severely or terminally ill
      patients have an advance directive in their medical record, and physicians are
      accurate only about 65% of the time when predicting patient preferences for
      intensive care. Decision aids can support the advance care planning process by
      providing a structured approach to informing patients about care options and
      prompting them to document and communicate their preferences. This review,
      commissioned as a technical brief by the Agency for Healthcare Research and
      Quality Effective Health Care Program, provides a broad overview of current use
      of and research related to decision aids for adult advance care planning. Using
      interviews of key informants and a search of the gray and published literature
      from January 1990 to May 2014, the authors found that many decision aids are
      widely available but are not assessed in the empirical literature. The 16
      published studies testing decision aids as interventions for adult advance care
      planning found that most are proprietary or not publicly available. Some are
      constructed for the general population, whereas others address disease-specific
      conditions that have more predictable end-of-life scenarios and, therefore, more
      discrete choices. New decision aids should be designed that are responsive to
      diverse philosophical perspectives and flexible enough to change as patients gain
      experience with their personal illness courses. Future efforts should include
      further research, training of advance care planning facilitators, dissemination
      and access, and tapping potential opportunities in social media or other
      technologies. 

PMID- 25069710
TI  - A preorganized metalloreceptor for alkaline earth ions showing calcium versus
      magnesium selectivity in water: biological activity of selected metal complexes.
AB  - The N,N'-bis[(3-hydroxy-4-pyron-2-yl)methyl]-N,N'-dimethylethylendiamine (Malten
      = L) forms the highly stable [CuH(-2)L] species in water, in which the converging
      maltol oxygen atoms form an electron-rich area able to host hard metal ions. When
      considering the alkaline earth series (AE), the [Cu(H(-2)L)] species binds all
      metal ions, with the exception of Mg(2+), exhibiting the relevant property to
      discriminate Ca(2+) versus Mg(2+) at physiological pH 7.4; the binding of the AE
      metal is visible to the naked eye. The stability constant values of the
      trinuclear [AE{Cu(H(-2)L)}2](2+) species formed reach the maximum for Ca(2+) (log
      K=7.7). Ca(2+) also forms a tetranuclear [Ca{Cu(H(-2)L)}]2(4+) species at a high
      Ca(2+) concentration. Tri- and tetranuclear calcium complexes show blue- and pink
      colored crystals, respectively. [Cu(H(-2)L)] is the most active species in
      inducing DNA alterations. The DNA damages are compatible with its hydrolytic
      cleavages.

PMID- 25069715
TI  - Israeli forces attack medical facilities in Gaza and destroy brand new hospital.

PMID- 25069713
TI  - Necrotizing soft tissue infections: review and current concepts in treatment,
      systems of care, and outcomes.

PMID- 25069714
TI  - Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid
      arthritis patients to respond to methotrexate treatment.
AB  - BACKGROUND: KIR genes coding for natural killer cell immunoglobulin-like
      receptors, KIR, influence the effector and regulatory function of NK cells as
      well as some subpopulations of T lymphocytes (e.g. CD4+CD28-KIR+) depending on
      presence of ligands (particularly HLA-C molecules). KIR-KIR ligand interaction
      may lead to the development of autoimmune disorders, including rheumatoid
      arthritis (RA). However, their role in the response of RA patients to
      methotrexate therapy is not known. METHODS: KIR genes and KIR-ligand (HLA-C C1/C2
      allomorphs) genotyping was performed using the PCR-SSP method in 312 RA patients
      (179 classified as good responders and 133 as poor responders using DAS28
      criteria). Thus, we evaluated the association of KIR genes and HLA-C allomorphs
      with the response to methotrexate (MTX) treatment. RESULTS: We observed that
      patients possessing the full-length KIR2DS4 (KIR2DS4f) gene had a lower chance of
      responding in comparison to KIR2DS4f-negative cases. This phenomenon was observed
      both in erosive disease (ED) and rheumatoid factor (RF) positive and in ED- and
      RF-negative patients. Interestingly, the observed effect of the KIR2DS4f gene was
      strongest in individuals possessing medium values (20-33 mm/h) of the erythrocyte
      sedimentation rate (ESR). Patients with high ESR values had low probability and,
      in contrast, patients with low ESR had a high probability of MTX response, and
      the presence of KIR2DS4f did not affect their outcome. Additionally, we show that
      the KIR2DS4f effect did not depend on the presence of either C1 or C2 allomorphs.
      CONCLUSION: Our results suggest that the response of RA patients with medium ESR
      values to MTX treatment may be dependent on the full-length KIR2DS4 gene.

PMID- 25069716
TI  - Effects of exogenous spermidine on photosynthetic capacity and expression of
      Calvin cycle genes in salt-stressed cucumber seedlings.
AB  - We investigated the effects of exogenous spermidine (Spd) on growth,
      photosynthesis and expression of the Calvin cycle-related genes in cucumber
      seedlings (Cucumis sativus L.) exposed to NaCl stress. Salt stress reduced net
      photosynthetic rates (PN), actual photochemical efficiency of PSII (PhiPSII) and
      inhibited plant growth. Application of exogenous Spd to salinized nutrient
      solution alleviated salinity-induced the inhibition of plant growth, together
      with an increase in PN and PhiPSII. Salinity markedly reduced the maximum
      carboxylase activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Vcmax),
      the maximal velocity of RuBP regeneration (Jmax), triose-phosphate utilization
      capacity (TPU) and carboxylation efficiency (CE). Spd alleviated the negative
      effects on CO2 assimilation induced by salt stress. Moreover, Spd significantly
      increased the activities and contents of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) and fructose-1,6-biphosphate aldolase (ALD;
      aldolase) in the salt-stressed cucumber leaves. On the other hand, salinity up
      regulated the transcriptional levels of ribulose-1,5-bisphosphate (RCA),
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribrokinase (PRK) and
      down-regulated the transcriptional levels of ribulose-1,5-bisphosphate
      carboxylase/oxygenase large subunit (RbcL), ribulose-1,5-bisphosphate
      carboxylase/oxygenase small subunit (RbcS), ALD, triose-3-phosphate isomerase
      (TPI), fructose-1,6-bisphosphate phosphatase (FBPase) and 3-phosphoglyceric acid
      kinase (PGK). However, Spd application to salt-stressed plant roots counteracted
      salinity-induced mRNA expression changes in most of the above-mentioned genes.
      These results suggest that Spd could improve photosynthetic capacity through
      regulating gene expression and activity of key enzymes for CO2 fixation, thus
      confers tolerance to salinity on cucumber plants.

PMID- 25069718
TI  - High-resolution melting (HRM) assay for the detection of recurrent BRCA1/BRCA2
      germline mutations in Tunisian breast/ovarian cancer families.
AB  - Germline deleterious mutations in the BRCA1/BRCA2 genes are associated with an
      increased risk for the development of breast and ovarian cancer. Given the large
      size of these genes the detection of such mutations represents a considerable
      technical challenge. Therefore, the development of cost-effective and rapid
      methods to identify these mutations became a necessity. High resolution melting
      analysis (HRM) is a rapid and efficient technique extensively employed as high
      throughput mutation scanning method. The purpose of our study was to assess the
      specificity and sensitivity of HRM for BRCA1 and BRCA2 genes scanning. As a first
      step we estimate the ability of HRM for detection mutations in a set of 21
      heterozygous samples harboring 8 different known BRCA1/BRCA2 variations, all
      samples had been preliminarily investigated by direct sequencing, and then we
      performed a blinded analysis by HRM in a set of 68 further sporadic samples of
      unknown genotype. All tested heterozygous BRCA1/BRCA2 variants were easily
      identified. However the HRM assay revealed further alteration that we initially
      had not searched (one unclassified variant). Furthermore, sequencing confirmed
      all the HRM detected mutations in the set of unknown samples, including
      homozygous changes, indicating that in this cohort, with the optimized assays,
      the mutations detections sensitivity and specificity were 100 %. HRM is a simple,
      rapid and efficient scanning method for known and unknown BRCA1/BRCA2 germline
      mutations. Consequently the method will allow for the economical screening of
      recurrent mutations in Tunisian population.

PMID- 25069717
TI  - Increase of nerve growth factor levels in the human herniated intervertebral
      disc: can annular rupture trigger discogenic back pain?
AB  - INTRODUCTION: Nerve growth factor (NGF) has an important role in the generation
      of discogenic pain. We hypothesized that annular rupture is a trigger for
      discogenic pain through the action of NGF. In this study, the protein levels of
      NGF in discs from patients with disc herniation were examined and compared with
      those from discs of patients with other lumbar degenerative disc diseases.
      METHODS: Patients (n = 55) with lumbar degenerative disc disease treated by
      surgery were included. Nucleus pulposus tissue (or herniated disc tissue) was
      surgically removed and homogenized; protein levels were quantified using an
      enzyme-linked immunosorbent assay (ELISA) for NGF. Levels of NGF in the discs
      were compared between 1) patients with herniated discs (herniated group) and
      those with other lumbar degenerative disc diseases (non-herniated group), and 2)
      low-grade and high-grade degenerated discs. Patient's symptoms were assessed
      using a visual analog scale (VAS) and the Oswestry disability index (ODI); the
      influence of NGF levels on pre- and post-operative symptoms was examined.
      RESULTS: Mean levels of NGF in discs of patients were significantly higher in
      herniated discs (83.4 pg/mg total protein) than those in non-herniated discs
      (68.4 pg/mg). CONCLUSIONS: This study reports that NGF increased in herniated
      discs, and may play an important role in the generation of discogenic pain.
      Analysis of patient symptoms revealed that pre-operative NGF levels were related
      to post-operative residual lower extremity pain and LBP in motion. The results
      suggest that NGF in the disc is related to pain generation, however, the impact
      of NGF on generation of LBP varies in individual patients.

PMID- 25069719
TI  - Introduction of highly resistant bacteria into a hospital via patients
      repatriated or recently hospitalized in a foreign country.
AB  - We describe the prevalence of carriage and variables associated with introduction
      of highly drug-resistant microorganisms (HDRMO) into a French hospital via
      patients repatriated or recently hospitalized in a foreign country. The
      prevalence of HDRMO was 11% (15/132), with nine carbapenamase-producing
      Enterobacteriaceae, nine carbapenem-resistant Acinetobacter baumannii and six
      glycopeptide-resistant enterococci. Half of the admitted patients (63/132, 48%)
      were colonized with extended spectrum beta-lactamase-producing Enterobacteriaceae
      (ESBLPE). Among the four episodes with secondary cases, three involved A.
      baumannii. 

PMID- 25069720
TI  - The anti-atherogenic effects of berberine on foam cell formation are mediated
      through the upregulation of sirtuin 1.
AB  - Berberine (BBR) is a botanical alkaloid that has been reported to have effects in
      cardiovascular diseases; however, the mechanisms involved are not yet fully
      understood. In the present study, the protective effects of BBR were evaluated,
      and the underlying molecular mechanisms were investigated. The effects of a
      combination of atorvastatin and BBR on foam cell formation were also
      investigated. THP-1-derived macrophages were pre-treated with BBR (5, 10 and 20
      mg/l) for 2 h prior to the addition of oxidized low density lipoprotein (ox-LDL;
      50 mg/l). Small interfering RNA (siRNA) targeting sirtuin 1 (SIRT1) and the
      adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor, compound C,
      were used to investigate the mechanisms through which BBR exerts its effects. To
      determine the effect of a combination of atorvastatin and BBR, the macrophages
      were treated with atorvastatin and BBR separately or jointly for 2 h, and then
      treated with ox-LDL (50 mg/l) or lipopolysaccharide (LPS; 10 uM) for 12 h. Oil
      Red O staining was used to detect foam cell formation. Lipid amounts were
      assessed by high-performance liquid chromatography (HPLC). Gene and protein
      expression was evaluated by RT-qPCR, western blot analysis and enzyme-linked
      immunosorbent assay (ELISA) carried out separately or jointly. The results from
      Oil Red O staining and HPLC revealed that BBR effectively suppressed foam cell
      formation and lipid and cholesterol accumulation. Furthermore, BBR upregulated
      the expression of SIRT1 and AMPK and downregulated the expression of peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma). Pre-treatment of the cells
      with SIRT1-siRNA or compound C attenuated the anti-atherosclerotic effects of
      BBR. The results obtained in the present study demonstrate that the combination
      of atorvastatin and BBR is more effective in inhibiting foam cell formation than
      using atorvastatin alone. These data suggest that BBR suppresses foam cell
      formation by activating the AMPK-SIRT1-PPAR-gamma pathway and diminishing the
      uptake of ox-LDL. Combination therapy with BBR and atorvastatin was more
      effective in preventing atherosclerotic processes than atorvastatin alone.

PMID- 25069723
TI  - Regulation of mitochondrial poly(ADP-Ribose) polymerase activation by the beta
      adrenoceptor/cAMP/protein kinase A axis during oxidative stress.
AB  - We investigated the regulation of mitochondrial poly(ADP-ribose) polymerase 1
      (PARP1) by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)
      system during oxidative stress in U937 monocytes. Oxidative stress induced an
      early (10 minutes) mitochondrial DNA damage, and concomitant activation of PARP1
      in the mitochondria. These early events were followed by a progressive
      mitochondrial oxidant production and nuclear PARP1 activation (by 6 hours). These
      processes led to a functional impairment of mitochondria, culminating in cell
      death of mixed (necrotic/apoptotic) type. beta-Adrenoceptor blockade with
      propranolol or inhibition of its downstream cAMP/PKA signaling attenuated, while
      beta-adrenoceptor agonists and cAMP/PKA activators enhanced, the oxidant-mediated
      PARP1 activation. In the presence of cAMP, recombinant PKA directly
      phosphorylated recombinant PARP1 on serines 465 (in the automodification domain)
      and 782 and 785 (both in the catalytic domain). Inhibition of the beta-adrenergic
      receptor/cAMP/PKA axis protected against the oxidant-mediated cell injury.
      Propranolol also suppressed PARP1 activation in peripheral blood leukocytes
      during bacterial lipopolysaccharide (LPS)-induced systemic inflammation in mice.
      We conclude that the activation of mitochondrial PARP1 is an early, active
      participant in oxidant-induced cell death, which is under the control of beta
      adrenoceptor/cAMP/PKA axis through the regulation of PARP1 activity by PARP1
      phosphorylation. 

PMID- 25069724
TI  - Modulation, bioinformatic screening, and assessment of small molecular peptides
      targeting the vascular endothelial growth factor receptor.
AB  - Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) are important
      factors in tumor growth and metastasis. Molecular probes or drugs designed to
      target VEGF/VEGFR interactions are crucial in tumor molecular imaging and
      targeted therapy. Bioinformatic methods enable molecular design based on the
      structure of bio-macromolecules and their interactions. This study was aimed to
      identify tumor-targeting small-molecule peptides with high affinity for VEGFR
      using bioinformatics screening. The VEGFR extracellular immunoglobulin-like
      modules Ig1-Ig3 were used as the target to systematically alter the primary
      peptide sequence of VEGF125-136. Molecular docking and surface functional group
      interaction methods were combined in an in silico screen for polypeptides, which
      in theory, would have higher affinities for VEGFR. In vitro receptor competition
      binding assays were used to assess the affinity of the putative VEGFR-binding
      polypeptides. Rhodamine-conjugated peptides were used to label and visualize
      peptide-binding sites on A549 cells. Using bioinformatic screening, we identified
      20 polypeptides with potentially higher affinity for VEGFR. The polypeptides were
      capable of inhibiting the binding of (125)I-VEGF to VEGFR in a dose-dependent
      manner. The IC50 values of QKRKRKKSRKKH and RKRKRKKSRYIVLS (80 and 185 nmol/L,
      respectively) were significantly lower than that of VEGF125-136 (464 nmol/L);
      thus, the affinity of these peptides for VEGFR was 6- and 2.5-fold higher,
      respectively, than that of VEGF125-136. Rhodamine labeling of A549 cells revealed
      peptide binding mainly on the plasma membrane and in the cytoplasm. Bioinformatic
      approaches hold promise for the development of molecular imaging probes. Using
      this approach, we designed two peptides that showed higher affinity toward VEGFR.
      These polypeptides may be used as molecular probes or drugs targeting VEGFR,
      which can be utilized in molecular imaging and targeted therapy of certain
      tumors.

PMID- 25069725
TI  - Association of single nucleotide polymorphisms in tumor necrosis factor-alpha
      with cervical cancer susceptibility.
AB  - Tumor necrosis factor-alpha (TNF-alpha) polymorphisms have been reported to play
      an important role in the development of cervical cancer. But the results remain
      inconclusive. We performed this study to provide a comprehensive assessment of
      the association by means of a meta-analysis in which all published studies were
      included. The studies investigating the associations between cervical cancer risk
      and TNF-alpha polymorphisms were identified through PubMed, Embase, CNKI, and
      Chinese BioMedical Literature Database. OR and 95% CI (odds ratio and 95%
      confidence interval) were calculated using either the fixed or random effects
      model to assess the associations. We eventually included eighteen case-control
      studies of SNP -308 G>A and nine studies of SNP -238 G>A. Meta-analysis of the
      former polymorphism suggested significantly increased risk of cervical cancer
      associated with the A allele (OR 1.19, 95% CI 1.02-1.38). Subgroup analysis
      according to ethnicity showed similar results in Caucasians (A vs. G: OR 1.25,
      95% CI 1.02-1.54; AA vs. GG: OR 1.47, 95% CI 1.04-2.08; AA vs. GA+GG: OR 1.47,
      95% CI 1.04-2.08). For SNP -238 G>A, a protective association was observed in
      overall comparisons (A vs. G: OR 0.64, 95% CI 0.51-0.80; AA+GA vs. GG: OR 0.62,
      95% CI 0.49-0.79) and subgroup analysis of Caucasians (A vs. G: OR 0.67, 95% CI
      0.53-0.83; AA+GA vs. GG: OR 0.65, 95% CI 0.51-0.82). Our meta-analysis indicates
      that TNF-alpha polymorphisms may confer susceptibility to cervical cancer in an
      ethic-specific fashion.

PMID- 25069726
TI  - Therapeutic touch for healing acute wounds.
AB  - BACKGROUND: Therapeutic Touch (TT) is an alternative therapy that has gained
      popularity over the past two decades for helping wounds to heal. Practitioners
      enter a meditative state and pass their hands above the patient's body to find
      and correct any imbalances in the patient's 'life energy' or chi. Scientific
      instruments have been unable to detect this energy. The effect of TT on wound
      healing has been expounded in anecdotal publications. OBJECTIVES: To identify and
      review all relevant data to determine the effects of TT on healing acute wounds.
      SEARCH METHODS: In January 2014, for this fifth update, we searched The Cochrane
      Wounds Group Specialised Register; The Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process &
      Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. SELECTION CRITERIA:
      All randomised or quasi-randomised controlled trials, which compared the effect
      of TT with a placebo, another treatment, or no treatment control were considered.
      Studies which used TT as a stand-alone treatment, or as an adjunct to other
      therapies, were eligible. DATA COLLECTION AND ANALYSIS: One author (DO'M)
      determined the eligibility for inclusion of all trials in the review. Both
      authors conducted data extraction and evaluation of trial validity independently.
      Each trial was assessed using predetermined criteria. MAIN RESULTS: No new trials
      were identified for this update. Four trials in people with experimental wounds
      were included. The effect of TT on wound healing in these studies was variable.
      Two trials (n = 44 & 24) demonstrated a significant increase in healing
      associated with TT, while one trial found significantly worse healing after TT
      and the other found no significant difference. All trials are at high risk of
      bias. AUTHORS' CONCLUSIONS: There is no robust evidence that TT promotes healing
      of acute wounds.

PMID- 25069728
TI  - Sexual dysfunction: Microtissue injection enhances erectile function.

PMID- 25069730
TI  - Prostate cancer: Brachyury--a biomarker for progression and prognosis?

PMID- 25069731
TI  - Male factor infertility: Prediction models for assisted reproductive technology.

PMID- 25069733
TI  - Paediatrics: New cryptorchidism guidelines reach a consensus.

PMID- 25069734
TI  - Prostate cancer: Say no to ADT for localized disease.

PMID- 25069736
TI  - Incontinence: A role for the microbiome in urge incontinence?

PMID- 25069737
TI  - The safety of testosterone supplementation therapy in prostate cancer.
AB  - Patients with prostate cancer can present with hypogonadism and experience health
      and quality-of-life declines related to low testosterone levels. Despite
      generations of urological dogma suggesting that testosterone supplementation
      therapy (TST) for hypogonadism causes prostate-cancer progression, a review of
      the contemporary literature provides evidence to the contrary. The prostate
      saturation model suggests that the androgen receptor (AR) is saturated at serum
      testosterone levels of 150-200 ng/dl, and that additional serum testosterone
      above this level has limited, if any, effects within the prostate. Indeed,
      studies in the modern era of PSA assessments indicate that TST does not affect
      prostate size, intraprostatic testosterone levels, or prostate-cancer
      progression, provided the baseline serum testosterone level is greater than this
      AR saturation point. However, the body of data on this subject comes from a small
      number of cases, and TST should only be administered to patients with prostate
      cancer after thorough discussions of the risks and benefits, with subsequent
      careful monitoring. 

PMID- 25069738
TI  - Interrater reliability of the Observer Rating of Medication Taking scale in an
      inpatient mental health facility.
AB  - Non-adherence to medication remains a major barrier to recovery from mental
      illnesses. Identification of those patients likely to experience adherence
      difficulties is best undertaken during inpatient treatment, prior to discharge
      into the community. More objective assessments of adherence behaviours might
      assist staff to more effectively target support to those patients most in need.
      This study investigated the interrater reliability of an inpatient behavioural
      observation scale of patient engagement with medication: the Observer Rating of
      Medication Taking (ORMT) scale. Eight mental health nurses working in a
      psychiatric hospital inpatient setting were trained in the use of the ORMT using
      video-based vignettes. Working in pairs, staff then independently rated adherence
      behaviours of 13 inpatients in a rehabilitation unit (total of 160 ratings) over
      a 1-week period. Concurrently, two expert raters also undertook independent
      ratings of patient medication-taking behaviour using the ORMT. Interrater
      reliability was assessed across both staff and expert raters. The results
      indicated that the ORMT has satisfactory interrater reliability, and can be
      appropriately used in an inpatient setting. The observational location of raters
      on the ward influenced the range of medication-taking behaviours observed, and
      thus the extent of concordance between raters. Further research to determine if
      the ORMT predicts adherence in the community is warranted.

PMID- 25069739
TI  - In human basophils, IL-3 selectively induces RANKL expression that is modulated
      by IgER-dependent and IgER-independent stimuli.
AB  - BACKGROUND: Receptor activator of NF-kappaB ligand (RANKL) is expressed as either
      surface (hRANKL1, hRANKL2) or soluble (hRANKL3) form. RANKL is involved in
      multifaceted processes of immunoregulation and bone resorption such as they occur
      in rheumatoid arthritis (RA). Interestingly, activated basophils, which are
      effector cells in allergic inflammation, contribute to the progress of collagen
      induced arthritis (CIA), a mouse model for RA. Here, we investigate under which
      conditions human basophils express RANKL. METHODS: Among other stimuli, basophils
      were cultured with IL-3 alone. Alternatively, as a secondary stimulus, IgER
      dependent or IgER-independent agents were added simultaneously either with IL-3
      or after prolonged IL-3 culturing. Expression of RANKL protein and mRNA was
      analyzed by flow cytometry, ELISA, and real-time PCR. A coculture system was
      applied to investigate biological activity of basophil-derived RANKL. RESULTS: We
      show that in human basophils, IL-3 but no other stimulus induces de novo
      expression of soluble and surface RANKL, of which the latter enhances survival of
      MoDC. Upon simultaneous stimulation, IgER cross-linking reduces surface RANKL
      expression, while IgER-independent stimuli have no effect. This is in contrast to
      consecutive stimulation, as triggering with both IgER-dependent and IgER
      independent stimuli enhances RANKL expression, particularly in its soluble form.
      Real-time PCR analysis shows that RANKL expression is mainly regulated at the
      mRNA level. CONCLUSION: This study identifies IL-3 as a potent inducer of RANKL
      expression in human basophils, suggesting them to interact with bone physiology
      and activation of immune cells. IgER-dependent and IgER-independent stimuli
      modulate the IL-3-mediated RANKL expression in a time- and stimulus-dependent
      fashion.

PMID- 25069740
TI  - Secretory clusterin is upregulated in rats with pulmonary arterial hypertension
      induced by systemic-to-pulmonary shunts and exerts important roles in pulmonary
      artery smooth muscle cells.
AB  - AIM: Phenotype modification of pulmonary artery smooth muscle cells (PASMCs)
      (excessive proliferation, migration and impaired apoptosis) plays central roles
      in pulmonary vascular remodelling of pulmonary arterial hypertension (PAH);
      however, the potential mechanism and contributing factors involved in the
      phenotype alteration in PASMCs are still not completely elucidated. This study
      attempted to investigate the expression pattern of secretory clusterin (sCLU), a
      prosurvival protein, in systemic-to-pulmonary shunt-induced PAH rats and the
      potential roles of sCLU in pulmonary vascular remodelling. METHODS: An original
      rat model of systemic-to-pulmonary shunt-induced PAH was established by combined
      surgery as we previously reported. Lung tissues were harvested at specific time
      points for real-time polymerase chain reaction, Western blot and
      immunohistochemisty analysis; meanwhile, plasma was collected for enzyme-linked
      immunosorbent assay. Cell culture experiments were performed using cultured human
      PASMCs (HPASMCs). RESULTS: Expression of sCLU was significantly increased in
      lungs exposed to systemic-to-pulmonary shunt. Moreover, plasma sCLU levels were
      markedly elevated with the progression of PAH in rats and also presented a
      positive correlation with pulmonary hemodynamic indices. In vitro cell culture
      assay indicated that sCLU expression and secretion increased with the phenotype
      modification of HPASMCs; furthermore, sCLU promoted HPASMCs proliferation,
      migration and apoptosis resistance, at least in part, via Erk1/2 and Akt
      signalling pathways. CONCLUSION: These results demonstrate that sCLU is
      functionally an important phenotype modulator of PASMCs, and its upregulation in
      lung tissues may exert a deteriorative role in pulmonary vascular remodelling.

PMID- 25069741
TI  - Simultaneous determination of gaseous and particulate carbonyls in air by
      coupling micellar electrokinetic capillary chromatography with molecular
      imprinting solid-phase extraction.
AB  - A novel method coupling molecular imprinting solid-phase extraction (MISPE) and
      micellar electrokinetic capillary chromatography (MEKC) was developed to enable
      the hourly determination of low level of ambient carbonyls, and study their
      partition between gaseous phase and particulate phase. With 2,4-dinitroaniline
      (DNAN) as dummy imprinting template, the unreacted 2,4-Dinitrophenylhydrazine
      (DNPH) in sampling solution could be removed effectively using MISPE, and an
      average recovery of 97+/-5.3% (n=5) for the carbonyl-DNPH derivatives was
      achieved. Owing to the high enrichment due to sample clean-up, and the
      improvement of MEKC separation efficiency, many low abundant carbonyls could be
      detected by hourly in the field study. 

PMID- 25069742
TI  - Fast procedure for the analysis of poly(hydroxyalkanoates) in bacterial cells by
      off-line pyrolysis/gas-chromatography with flame ionization detector.
AB  - Poly(hydroxyalkanoates) (PHAs) are polyesters formed by saturated short chain
      hydroxyacids, among which 3-hydroxybutanoic (HB) and 3-hydroxypentanoic (3
      hydroxyvalerate, HV) are the most common monomers of homopolymers (e.g. poly(3
      hydroxybutyrate), PHB) and copolymers (e.g. poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate), PHB-HC). The most widely used approach for their determination
      is the polymer methanolysis followed by gas chromatography-mass spectrometry (GC
      MS) analysis of the methylated monomers; this procedure generally requires the
      use of additional reagents (e.g. sulfuric acid) and is performed with harmful
      chlorinated solvents, such as chloroform. The development of fast routine
      solventless methods for the quantitative determination of PHAs and their
      monomeric composition is highly desirable to reduce sample pretreatment, speed up
      the analysis and decrease overall costs. It has been reported that under thermal
      treatment (e.g. pyrolysis, Py), PHAs are degraded in high yield (>40%, w/wPHA)
      into the corresponding 2-alkenoic acid (e.g. crotonic acid from PHB). This work
      aimed at investigating this reaction for direct analysis of PHAs in bacterial
      cells. The sample was directly subjected to pyrolysis and trapped pyrolysis
      products were analyzed by GC-FID. Off-line Py/GC-FID was first optimized on pure
      polymers with different monomer composition (PHB, PHB-HV, PHB-HC) and then
      applied to bacterial samples deriving from both mixed microbial cultures or
      selected strains, containing various types and amounts of PHAs. The Py/GC-FID
      method provided RSD <15% range, limit of detection of 100MUg (1% PHAs in
      biomass), and results comparable to that of methanolysis (R(2)=0.9855), but with
      minimal sample pretreatment. 

PMID- 25069743
TI  - Ethyl acetate-n-butanol gradient solvent system for high-speed countercurrent
      chromatography to screen bioactive substances in okra.
AB  - High-speed countercurrent chromatographic separation (HSCCC) possesses the
      property of zero-loss of sample, which is very useful for the screening of
      bioactive components. In the present study, the ethyl acetate-n-butanol gradient
      HSCCC solvent system composed of n-hexane-ethyl acetate-n-butanol-water was
      investigated for the screening of bioactive substances. To screen the
      antiproliferative compounds in okra extract, we used the stationary phase ethyl
      acetate-n-butanol-water (1:1:10) as the stationary phase, and eluted the
      antiproliferative components by 6-steps of gradient using mobile phases n-hexane
      ethyl acetate (1:2), n-hexane-ethyl acetate (1:4), n-hexane-ethyl acetate (0:4),
      n-butanol-ethyl acetate (1:4) n-butanol-ethyl acetate (1:2), n-butanol-ethyl
      acetate (2:2), and n-butanol-ethyl acetate (2:1). The fractions collected from
      HSCCC separation with the gradient solvent system were assayed for
      antiproliferative activity against cancer cells. Bioactive components were
      identified: a major anti-cancer compound, 4'-hydroxy phenethyl trans-ferulate,
      with middle activity, and a minor anti-cancer compound, carolignan, with strong
      activity. The result shows that the gradient solvent system is potential for the
      screening of bioactive compounds from natural products. 

PMID- 25069744
TI  - Multianalyte determination of the kinetic rate constants of drug-cyclodextrin
      supermolecules by high performance affinity chromatography.
AB  - The kinetics of the dissociation is fundamental to the formation and the in vivo
      performance of cyclodextrin supramolecules. The individual determination of the
      apparent dissociation rate constant (kd,app) using high performance affinity
      chromatography (HPAC) is a tedious process requiring numerous separate studies
      and massive data fitting. In this study, the multianalyte approach was employed
      to simultaneously measure the kd,app values of three drugs through one injection
      based on the investigation of the dependence of drug-cyclodextrin interaction
      kinetics on the mobile phase composition. As a result, the kd,app values
      increased when decreasing the ion strength, increasing the ionization of drugs
      and adding extra organic solvents. The values of kd,app for acetaminophen,
      phenacetin and S-flurbiprofen estimated by the multianalyte approach were 8.54+/
      1.81, 5.36+/-0.94 and 0.17+/-0.02s(-1), respectively, which were in good
      agreement with those determined separately (8.31+/-0.58, 5.01+/-0.42 and 0.15+/
      0.01s(-1)). For both of the single and multiple flow rate peak profiling methods,
      the results of the multianalyte approach were statistically equivalent with that
      of the single compound analysis for all of the three drugs (p>0.05). The
      multianalyte approach can be employed for the efficient evaluation of the drug
      cyclodextrin kinetics with less variance caused by cyclodextrin column bleeding. 

PMID- 25069745
TI  - Dual labeling for simultaneous determination of nitric oxide, glutathione and
      cysteine in macrophage RAW264.7 cells by microchip electrophoresis with
      fluorescence detection.
AB  - A simple, rapid and efficient method based on microchip electrophoresis coupled
      with fluorescence detection (MCE-FLD) was developed for simultaneous
      determination of nitric oxide (NO), glutathione (GSH) and cysteine (Cys) using
      dual labeling strategy. Two highly reactive fluorogenic probes, 1,3,5,7
      tetramethyl-8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacene (DAMBO) and
      1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)-difluoroboradiaza-s-indacene (TMPAB-o
      M), were used for labeling NO and thiols, respectively, under physiological
      conditions. The rapid separation and sensitive detection of the derivatives were
      achieved on a glass microchip within 70s in a running buffer of 20mM H3Cit
      Na2HPO4 solution (pH 7.4) containing 15% (v/v) acetonitrile at a separation
      voltage of 2400V. The limits of detection (S/N=3) for NO, GSH and Cys were 7.0,
      3.0 and 2.0nM, respectively. The proposed method was validated by measuring
      intracellular levels of NO and biothiols in macrophage RAW264.7 cells. 

PMID- 25069746
TI  - Estimation of the effects of longitudinal temperature gradients caused by
      frictional heating on the solute retention using fully porous and superficially
      porous sub-2MUm materials.
AB  - In this study, the retention changes induced by frictional heating were evaluated
      for model small compounds (150-190Da) and a small protein, namely insulin
      (5.7kDa). For this purpose, the effect of longitudinal temperature gradient
      caused by frictional heating was experimentally dissociated from the combined
      effect of pressure and frictional heating, by working either in constant and
      variable inlet pressure modes. Various columns packed with core-shell and fully
      porous sub-2MUm particles were tested. It appears that frictional heating was
      less pronounced on the column packed with smallest core-shell particles (1.3MUm),
      compared to the ones packed with core-shell and fully porous particles of 1.7
      1.8MUm. This observation was attributed to the low permeability of this material
      and the fact that it can only be employed in a restricted flow rate range, thus
      limiting the generated heat power. In addition, the thermal conductivity of the
      solid silica core of superficially porous particles (1.4W/m/K) is known to be
      much larger than that of fully porous silica. Then, the heat dissipation is
      improved. However, if systems with higher pressure capability would be available
      and the mechanical stability of 1.3MUm core-shell material was extended to e.g.
      2000bar, the retention would be more severely impacted. At 2000bar, ~4.4W heat
      power and +30 degrees C increase at column outlet temperature is expected. Last
      but not least, when analyzing large molecules, the impact of pressure overcomes
      the frictional heating effects. This was demonstrated in this study with insulin
      (~5.7kDa). 

PMID- 25069748
TI  - Middle Eastern nursing perspective from Bahrain.

PMID- 25069747
TI  - Strategies to prevent brain metastasis in high-risk non-small-cell lung cancer:
      lessons learned from a randomized study of maintenance temozolomide versus
      observation.
AB  - BACKGROUND: This study investigated whether maintenance temozolomide (TMZ) after
      definitive therapy for locally advanced non-small-cell lung cancer (NSCLC) could
      decrease the incidence of brain metastasis (BM). PATIENTS AND METHODS: Eligible
      patients included those with stage IIIA, IIIB, or IV (for stage IV, only with
      malignant pleural/pericardial effusion) NSCLC with no BM at diagnosis and stable
      disease, partial response, or complete response after first-line chemotherapy
      using at least 2 agents. Patients were randomized to observation or TMZ (75
      mg/m(2) for 21 consecutive days followed by a 7-day rest for up to 6 cycles or
      progression). The primary end point was incidence of radiographically diagnosed
      BM within 12 months from day 1 of first-line chemotherapy. Secondary end points
      included overall survival (OS), time to progression, incidence of BM at first
      progression, and toxicity. RESULTS: The study was closed early on the basis of a
      futility analysis; 45 of 53 enrolled patients were evaluable from an original
      target of 100. No difference was noted in the incidence of BM at 1 year in the
      TMZ and observation groups (18% and 13%, respectively), in median time to
      progression (11.7 and 10.7 months, respectively), or in median OS (27.1 and 22.5
      months, respectively). Common Terminology Criteria for Adverse Events grade 3 or
      4 adverse events were 46% in the TMZ group and 19% in the observation group.
      CONCLUSIONS: TMZ monotherapy does not appear to decrease the incidence of BM in
      patients with locally advanced NSCLC. These results considered in the context of
      the existing literature have implications for future clinical trial design.

PMID- 25069749
TI  - Design and characterization of short antimicrobial peptides using leucine zipper
      templates with selectivity towards microorganisms.
AB  - Design of antimicrobial peptides with selective activity towards microorganisms
      is an important step towards the development of new antimicrobial agents. Leucine
      zipper sequence has been implicated in cytotoxic activity of naturally occurring
      antimicrobial peptides; moreover, this motif has been utilized for the design of
      novel antimicrobial peptides with modulated cytotoxicity. To understand further
      the impact of substitution of amino acids at 'a' and/or 'd' position of a leucine
      zipper sequence of an antimicrobial peptides on its antimicrobial and cytotoxic
      properties four short peptides (14-residue) were designed on the basis of a
      leucine zipper sequence without or with replacement of leucine residues in its
      'a' and 'd' positions with D-leucine or alanine or proline residue. The original
      short leucine zipper peptide (SLZP) and its D-leucine substituted analog, DLSA
      showed comparable activity against the tested Gram-positive and negative bacteria
      and the fungal strains. The alanine substituted analog (ASA) though showed
      appreciable activity against the tested bacteria, it showed to some extent lower
      activity against the tested fungi. However, the proline substituted analog (PSA)
      showed lower activity against the tested bacterial or fungal strains.
      Interestingly, DLSA, ASA and PSA showed significantly lower cytotoxicity than
      SLZP against both human red blood cells (hRBCs) and murine 3T3 cells. Cytotoxic
      and bactericidal properties of these peptides matched with peptide-induced
      damage/permeabilization of mammalian cells and bacteria or their mimetic lipid
      vesicles suggesting cell membrane could be the target of these peptides. As
      evidenced by tryptophan fluorescence and acrylamide quenching studies the
      peptides showed similarities either in interaction or in their localization
      within the bacterial membrane mimetic negatively charged lipid vesicles. Only
      SLZP showed localization inside the mammalian membrane mimetic zwitterionic lipid
      vesicles. The results show significant scope for designing antimicrobial agents
      with selectivity towards microorganisms by substituting leucine residues at 'a'
      and/or 'd' positions of a leucine zipper sequence of an antimicrobial peptide
      with different amino acids. 

PMID- 25069750
TI  - Structure-activity relationships in ultrashort cationic lipopeptides: the effects
      of amino acid ring constraint on antibacterial activity.
AB  - Taking a minimalistic approach in efforts to lower the cost for the development
      of new synthetic antimicrobial peptides, ultrashort cationic lipopeptides were
      designed to mimic the amphiphilic nature crucial for their activity but with only
      a very short peptide sequence ligated to a lipidic acid. Nine ultrashort cationic
      lipopeptides were prepared to study the effects of ring constraint in the amino
      acid side chain of the peptide component. USCL-PCat1, consisting of only four L
      4R-aminoproline residues and acylated with palmitic acid at the N-terminus, was
      found to populate a polyproline II helical secondary conformation that is stable
      to different pHs and temperatures using circular dichroism. The synthesized
      lipopeptides were found to have a micellar structure in water using negative
      staining transmission electron microscopy. We found that constraining the side
      chain of the amino acid component is not beneficial to the antimicrobial
      activity. USCL-Dab1, USCL-Dab3 and USCL-K1 showed promising activity against a
      panel of laboratory reference and clinically isolated Gram-positive and Gram
      negative bacterial strains, some of which are multidrug resistant. No appreciable
      cytotoxicity against human monocytic THP-1 cells was observed up to
      concentrations of 20-40 uM for all synthesized compounds. Moreover, all USCLs did
      not induce the production of either pro-inflammatory cytokines or chemokines up
      to 40 uM. 

PMID- 25069751
TI  - US falls short of target for vaccinating adolescents against HPV.

PMID- 25069752
TI  - Effect of iterative reconstruction algorithms on peripheral MDCT angiography
      virtual histology plaque volumes: have we been overestimating disease burden?
AB  - Our objective was to compare plaque volumes of multidetector computed tomographic
      images reconstructed using adaptive statistical iterative reconstruction (ASIR),
      model-based iterative reconstruction (MBIR), and filtered back projection (FBP).
      We reviewed 25 patients for a total of 50 extremities imaged on the same scanner.
      Calcified plaque FBP volume (3468.2 +/- 2634.8 mm(3)) was higher than ASIR
      (2548.1 +/- 2166.5 mm(3)). Calcified plaque FBP volume was higher than MBIR
      (mean=2345.7 +/- 1935.4 mm(3)). Our findings suggest that traditional FBP methods
      overestimate disease compared to newer reconstruction methods.

PMID- 25069753
TI  - Endovascular management of thrombosed axillary artery to right atrium
      hemodialysis graft.
AB  - PURPOSE: To describe the salvage of a left axillary artery to right atrium
      hemodialysis graft using endovascular techniques. CASE REPORT: A 54-year-old man
      with multiple arteriovenous graft failures presented with a thrombosed left
      axillary artery to right atrium Gore-tex hemodialysis graft. The graft was
      salvaged using rheolytic catheter thrombectomy, mechanical thrombectomy, balloon
      angioplasty, and stenting. CONCLUSIONS: This single case report suggests that
      when axillary to right atrium grafts fail, various endovascular techniques can be
      employed to salvage the graft and maintain dialysis access.

PMID- 25069754
TI  - Seasonal variations cause morphological changes and altered spermatogenesis in
      the testes of viscacha (Lagostomus maximus).
AB  - This study complements the previous investigations of the reproductive biology of
      male viscachas, a rodent of a seasonal Hystricognathi that exhibits photoperiod
      induced morphological variations in the reproductive system. In the present
      study, a quantitative analysis of spermatogenesis was performed during the summer
      and the spring. Spermatogonial cells were analyzed to determine by
      immunolabelling for STRA8 and DAZL, which are essential for spermatogenesis. Six
      free-living male viscachas were captured, three animals in the summer during the
      period of reproductive activity and three animals in the spring during the period
      of testicular regression. The testes of the viscachas were collected and
      processed for light microscopy, macroscopic and immunochemical analyses. The germ
      and Sertoli cells present in the seminiferous tubules were quantitatively
      analyzed in each animal. The efficiency coefficient for spermatogonial mitosis,
      meiotic yield, overall spermatogenesis yield and Sertoli cell index, revealed
      that the Sertoli cells in male viscachas captured during the summer had a reduced
      capacity to structurally and nutritionally support the developing round
      spermatids compared with the male viscachas captured during the spring. The
      animals produced less sperm during the spring than the summer, suggesting a
      seasonal impact on spermatogenesis. Immunolabelling for STRA8 and DAZL was
      detected during summer and spring seasons. These results suggest that in seasonal
      rodents, such as the male viscachas, the photoperiod promotes significant changes
      in the testis and in the germ cell yield.

PMID- 25069755
TI  - Analysis of the interactome of ribosomal protein S19 mutants.
AB  - Diamond-Blackfan anemia, characterized by defective erythroid progenitor
      maturation, is caused in one-fourth of cases by mutations of ribosomal protein
      S19 (RPS19), which is a component of the ribosomal 40S subunit. Our previous work
      described proteins interacting with RPS19 with the aim to determine its
      functions. Here, two RPS19 mutants, R62W and R101H, have been selected to compare
      their interactomes versus the wild-type protein one, using the same functional
      proteomic approach that we employed to characterize RPS19 interactome. Mutations
      R62W and R101H impair RPS19 ability to associate with the ribosome. Results
      presented in this paper highlight the striking differences between the
      interactomes of wild-type and mutant RPS19 proteins. In particular, mutations
      abolish interactions with proteins having splicing, translational and helicase
      activity, thus confirming the role of RPS19 in RNA processing/metabolism and
      translational control. The data have been deposited to the ProteomeXchange with
      identifier PXD000640
      (http://proteomecentral.proteomexchange.org/dataset/PXD000640). 

PMID- 25069756
TI  - Nucleosome loss facilitates the chemotactic response of macrophages.
AB  - BACKGROUND: High mobility group box 1 (HMGB1) is a small nuclear protein with two
      functions. In the nucleus, it helps to wrap DNA around nucleosomes. When
      secreted, it recruits inflammatory cells and induces cytokine production. Before
      HMGB1 is secreted from inflammatory cells, it relocates to the cytoplasm, which
      partially or totally depletes cell nuclei of HMGB1. We previously showed that
      cells lacking HMGB1 contain 20% fewer nucleosomes and 30% more RNA transcripts
      levels genome-wide. OBJECTIVE: We hypothesized that the depletion of nuclear
      HMGB1 plays a role in inflammation that can enhance or complement the role of
      extracellular HMGB1. METHODS: We analysed the transcriptional profile of wild
      type and Hmgb1-/- mouse embryonic fibroblasts (MEFs) as a proxy for cells that
      have lost HMGB1 from their nuclei. We explored the transcriptome of wild-type and
      Hmgb1-/- macrophages differentiated in the presence of granulocyte-macrophage
      colony-stimulating factor, before and after exposure to LPS/IFN-gamma. In the
      same cells, histones and nuclear HMGB1 were quantified. RESULTS: We found that
      Hmgb1-/- MEFs show a transcriptional profile associated with stress and
      inflammation responses. Moreover, wild-type macrophages that have secreted HMGB1
      because of LPS/IFN-gamma exposure rapidly reduce their histone content as much as
      cells that genetically lack HMGB1. Importantly, unstimulated Hmgb1-/- macrophages
      activate transcriptional pathways associated with cell migration and chemotaxis.
      CONCLUSIONS: We suggest that nucleosome loss is an early event that facilitates
      transcriptional responses of macrophages to inflammation, particularly
      chemotaxis. HMGB1's dual roles in the nucleus and in the extracellular space
      appear to be complementary.

PMID- 25069757
TI  - Death due to complications of anhidrotic ectodermal dysplasia.
AB  - Ectodermal dysplasia comprises a group of disorders affecting ectodermal tissues.
      Severity depends on the genetic aberration; hyperpyrexia secondary to absence of
      sweat glands is a common complication. Treatment is supportive. This case report
      describes a 1-month, 27-day-old male infant with a diagnosis of X-linked
      recessive anhidrotic ectodermal dysplasia. On the day of his death, his mother
      swaddled him in a blanket and placed him on the couch at 5:30 am. When she picked
      him up at 8:00 am, he was unresponsive. At the emergency department, his rectal
      temperature was 40 degrees C. Postmortem blood culture was positive for group B
      streptococcus, a possible etiology for fever. It is vital to teach parents that
      close monitoring of children with ectodermal dysplasia is necessary, as an
      increase in body temperature can become life threatening. 

PMID- 25069758
TI  - [Analysis of type 2 diabetes-induced late effects based on administrative data of
      social insurance in Austria and implications for the evaluation of the DMP
      diabetes mellitus].
AB  - The present study analyses administrative data of medical services related to the
      distribution of diabetes mellitus type 2-induced late effects. Pseudonymous
      statutory health insurance data of all Austrian social security institutions for
      the years 2006/2007 in outpatient and inpatient (performance and diagnostic data)
      setting were used. Type 2 diabetics have been identified by prescribed
      medication. The specific late effects were defined as endpoints and the
      respective diagnoses and health performances were extracted. The study population
      included 7,945,774 insured. The percentage of the defined late effects was
      significantly higher in diabetics than in persons from the general population,
      with exception for kidney transplantation. The risk of a late effect was greatest
      among diabetics for an amputation. The results of this study can be used as a
      baseline for the evaluation of DMP diabetes. The administrative data used are
      limited for answering the defined research questions. Anyway, the data quality
      must be improved and unified in Austria. 

PMID- 25069759
TI  - Interferon alpha-2b gains high sustained response therapy for advanced essential
      thrombocythemia and polycythemia vera with JAK2V617F positive mutation.
AB  - OBJECTIVE: This open-label, prospective, observational study aimed to evaluate
      treatment response, efficacy therapy and safety to IFN alpha-2b for the essential
      thrombocythemia (ET) and polycythemia vera (PV) with JAK2V617F positive mutation.
      METHOD: A total of 123 ET patients received IFNalpha-2b therapy with JAK2V617F
      positive or negative mutation; and 136 PV patients with JAK2V617F(+) received
      IFNalpha-2b or hydroxyurea (HU) therapy according to random number assignment
      (ages 18-65 years old). RESULT: ET patients receiving IFN alpha-2b with
      JAK2V617F(+) had a greater advantage in overall hematologic response (OHR) than
      JAK2V617F(-) (83.3% versus 61.4%, P<0.01). For PV patients with JAK2V617F(+), IFN
      had no OHR superiority to HU (70.3% versus 70.8%, P>0.05), but which gained a
      greater satisfactory molecular response than HU (54.7% versus 19.4%, P<0.01). IFN
      significantly decreased the phlebotomy rate, which was better than HU for MPDs
      patients with OHR than HU (3.6% versus 65.7%, P<0.01). Furthermore, ET patients
      with JAK2V617F(+) demonstrated a definite advantage over JAK2V617F(-) in five
      year PFS (75.9% versus 47.6%, P<0.05). For PV patients with JAK2V617F(+), IFN
      alpha-2b was superior to HU in five-year PFS (66.3% versus 46.7%, P<0.01).
      Moreover, IFN alpha-2b also contributed to improved vasomotor symptoms in MPDs,
      and especially significantly decreased the incidence of distal paresthesias
      (14.1% versus 37.5%) and erythromelalgia (9.4% versus 29.2%) better than HU
      (P<0.01). Meanwhile, IFN did not observe the severe hematological adverse events
      in patients with PV or ET. CONCLUSION: The data confirmed that IFN alpha-2b
      benefited the patients with ET or PV, particularly for JAK2V617F(+) mutation.

PMID- 25069761
TI  - Orange rings at the periorbital area.

PMID- 25069760
TI  - Facts and artifacts in studies of gene expression in aneuploids and sex
      chromosomes.
AB  - Studies of gene expression in aneuploids have often made the assumption that
      measurements of RNA abundance from the varied chromosome will establish whether
      there is a dosage effect or compensation. Typical procedures of RNA isolation and
      use of equal amounts of RNA for quantitative estimates will not measure the total
      transcriptome size nor the absolute expression levels per cell. Use of internal
      endogenous standards or averages from unvaried chromosomes for normalizations
      makes the assumption that there are no global modulations across the genome.
      However, studies that use controls to test these assumptions reveal that there
      are in fact often modulations on all chromosomes. The same caveats apply to gene
      expression studies of sex chromosomes, which also involve changes in dosage of a
      small portion of the genome. Here, we describe some of the pitfalls of studies of
      aneuploidy and sex chromosome gene expression and review methods that have been
      used to avoid them. 

PMID- 25069762
TI  - Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of
      women with endometriosis: a pilot study.
AB  - Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies
      suggest that peritoneal fluid is a key inflammatory environment in the
      development and progression of the disease. This study analyzed the levels of two
      inflammatory factors - Galectin-3 and Stimulation Expressed Gene 2 - in the
      peritoneal fluid of 15 women affected by endometriosis and 8 controls. The
      peritoneal fluid was collected during laparoscopic surgery avoiding any form of
      contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal
      concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were
      significantly higher in endometriosis group than in controls (64.7 +/- 52.34
      versus 21.05 +/- 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not
      differ between the two groups. A significant positive correlation was found
      between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage
      of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while
      ST2 levels were positively associated with VAS score. Our results suggest that
      Gal-3 and ST2 could be implicated in the inflammatory process of the disease.
      Further studies are needed to identify markers of early diagnosis and to open new
      therapeutic avenues in endometriosis. 

PMID- 25069763
TI  - A green heterogeneous synthesis of N-doped carbon dots and their
      photoluminescence applications in solid and aqueous states.
AB  - Compared with traditional semiconductor quantum dots (QDs) and organic dyes,
      photoluminescent carbon dots (CDs) are superior because of their high aqueous
      solubility, robust chemical inertness, facile functionalization, high resistance
      to photobleaching, low toxicity and good biocompatibility. Herein, a green, large
      scale and high-output heterogeneous synthesis of N-doped CDs was developed by
      reacting calcium citrate and urea under microwave irradiation without the use of
      any capping agents. The obtained N-doped CDs with a uniform size distribution
      exhibit good aqueous solubility and yellowish-green fluorescence in the solid and
      aqueous states. These unique luminescence properties of N-doped CDs inspire new
      thoughts for applications as fluorescent powders, fluorescent inks, the growth of
      fluorescent bean sprouts, and fingerprint detection tools. 

PMID- 25069764
TI  - Gene expression profiles of patients with cerebral hematoma following spontaneous
      intracerebral hemorrhage.
AB  - The present study aimed to investigate the gene functions and expression profiles
      in perihematomal (PH) brain regions following spontaneous intracerebral
      hemorrhage. The gene expression profiles were downloaded from the Gene Expression
      Omnibus database under accession number GSE24265, which includes 11 brain samples
      from different regions, including four samples from PH areas, four from
      contralateral grey matter (CG) and three from contralateral white matter (CW).
      The gene expression profiles were pre-processed and the differentially expressed
      genes (DEGs) between PH and CG tissue, and PH and CW tissue were identified using
      R packages. The expression of genes in different tissues was analyzed by
      hierarchical clustering. Then, the interaction network between the DEGs was
      constructed using String software. Finally, Gene Ontology was performed and
      pathway analysis was conducted using FuncAssociate and Expression Analysis
      Systematic Explorer to identify the gene function. As a result, 399 DEGs were
      obtained between PH and CG, and 756 DEGs were identified between PH and CW. There
      were 35 common DEGs between the two groups. These DEGs may be involved in PH
      edema by regulating the calcium signaling pathway [calcium channel, voltage
      dependent, T-type, alpha1I subunit, Ca2+/calmodulin-dependent protein kinase II
      alpha (CAMK2A), ryanodine receptor 2 (RYR2) and inositol 1,4,5-trisphosphate
      receptor, type 1 (ITPR1)], cell proliferation (sphingosine kinase 1), neuron
      differentiation (Ephrin-A5) or extracellular matrix-receptor interaction
      [collagen, type I, alpha 2, laminin B1 (LAMB1), syndecan 2, fibronectin 1 and
      integrin alpha5 (ITGA5)]. A number of genes may cooperate to participate in the
      same pathway, such as ITPR1-RYR2, CAMK2A-RYR2 and ITGA5-LAMB1 interaction pairs.
      The present study provides several potential targets to decrease hematoma
      expansion and alleviate neuronal cell death following spontaneous intracerebral
      hemorrhage. 

PMID- 25069765
TI  - Ergonomics intervention through work organization solution: The way forward.

PMID- 25069766
TI  - Role of lifeguard beta-isoform in the development of breast cancer.
AB  - In the last century there has been great progress in the treatment of breast
      cancer by improving drug and radiation therapy as well as surgical techniques.
      Despite this development, breast cancer remains a major cause of death among
      women in Europe and the US. The cause of breast cancer at the cellular level is
      still not fully understood. In the present study, we investigated the expression
      of the Lifeguard beta-isoform in breast cancer tissues. In contrast to Lifeguard,
      the beta-isoform has one transmembrane domain less, which is the last of seven
      (99 bp), and due to this we suspect that the Lifeguard beta-isoform exhibits a
      different function. We determined the expression and function of the beta-isoform
      of Lifeguard in breast cancer cell lines (MCF-7 and MDA-MB-231), a human breast
      epithelial cell line (MCF10A) and in breast tumour tissue sections. Western
      blotting, PCR arrays and immunofluorescence were used to investigate the
      expression of Lifeguard and its beta-isoform. Moreover, we investigated the
      ability of Lifeguard beta-isoform expression to inhibit apoptosis induced by Fas.
      Our results indicated that Lifeguard beta-isoform is strongly expressed in breast
      tumour tissues. More notably, we demonstrated that Fas sensitivity was reduced in
      the MCF10A breast cells expressing the Lifeguard beta-isoform. Taken together,
      our findings indicate the role of the Lifeguard beta-isoform as an anti-apoptotic
      protein and provide further evidence of the potential of the Lifeguard beta
      isoform as a target for the development of novel therapeutic strategies. 

PMID- 25069767
TI  - Kava dermopathy in Fiji: an acquired ichthyosis?
AB  - Kava dermopathy is a common cutaneous effect of regular or heavy use of Kava, a
      psychoactive beverage consumed widely throughout the Pacific. In Fiji in 2012,
      over 1000 study participants underwent full skin examination, and kava dermopathy
      was a common cutaneous finding. The clinical manifestations of kava dermopathy
      share similarities with the spectrum of autosomal recessive congenital
      ichthyoses, predominantly lamellar ichthyosis. The pathogenesis of Kava
      dermopathy may be associated with a functional defect in one or more cytochrome
      P450 enzymes implicated in epidermal integrity, thus mimicking the genetic defect
      as seen in lamellar ichthyosis type 3. 

PMID- 25069768
TI  - Geometric correction method for 3D in-line X-ray phase contrast image
      reconstruction.
AB  - BACKGROUND: Mechanical system with imperfect or misalignment of X-ray phase
      contrast imaging (XPCI) components causes projection data misplaced, and thus
      result in the reconstructed slice images of computed tomography (CT) blurred or
      with edge artifacts. So the features of biological microstructures to be
      investigated are destroyed unexpectedly, and the spatial resolution of XPCI image
      is decreased. It makes data correction an essential pre-processing step for CT
      reconstruction of XPCI. METHODS: To remove unexpected blurs and edge artifacts, a
      mathematics model for in-line XPCI is built by considering primary geometric
      parameters which include a rotation angle and a shift variant in this paper.
      Optimal geometric parameters are achieved by finding the solution of a
      maximization problem. And an iterative approach is employed to solve the
      maximization problem by using a two-step scheme which includes performing a
      composite geometric transformation and then following a linear regression
      process. After applying the geometric transformation with optimal parameters to
      projection data, standard filtered back-projection algorithm is used to
      reconstruct CT slice images. RESULTS: Numerical experiments were carried out on
      both synthetic and real in-line XPCI datasets. Experimental results demonstrate
      that the proposed method improves CT image quality by removing both blurring and
      edge artifacts at the same time compared to existing correction methods.
      CONCLUSIONS: The method proposed in this paper provides an effective projection
      data correction scheme and significantly improves the image quality by removing
      both blurring and edge artifacts at the same time for in-line XPCI. It is easy to
      implement and can also be extended to other XPCI techniques.

PMID- 25069769
TI  - Extracting fetal heart beats from maternal abdominal recordings: selection of the
      optimal principal components.
AB  - This study presents a systematic comparison of different approaches to the
      automated selection of the principal components (PC) which optimise the detection
      of maternal and fetal heart beats from non-invasive maternal abdominal
      recordings.A public database of 75 4-channel non-invasive maternal abdominal
      recordings was used for training the algorithm. Four methods were developed and
      assessed to determine the optimal PC: (1) power spectral distribution, (2) root
      mean square, (3) sample entropy, and (4) QRS template. The sensitivity of the
      performance of the algorithm to large-amplitude noise removal (by wavelet de
      noising) and maternal beat cancellation methods were also assessed. The accuracy
      of maternal and fetal beat detection was assessed against reference annotations
      and quantified using the detection accuracy score F1 [2*PPV*Se / (PPV + Se)],
      sensitivity (Se), and positive predictive value (PPV). The best performing
      implementation was assessed on a test dataset of 100 recordings and the agreement
      between the computed and the reference fetal heart rate (fHR) and fetal RR (fRR)
      time series quantified.The best performance for detecting maternal beats (F1
      99.3%, Se 99.0%, PPV 99.7%) was obtained when using the QRS template method to
      select the optimal maternal PC and applying wavelet de-noising. The best
      performance for detecting fetal beats (F1 89.8%, Se 89.3%, PPV 90.5%) was
      obtained when the optimal fetal PC was selected using the sample entropy method
      and utilising a fixed-length time window for the cancellation of the maternal
      beats. The performance on the test dataset was 142.7 beats(2)/min(2) for fHR and
      19.9 ms for fRR, ranking respectively 14 and 17 (out of 29) when compared to the
      other algorithms presented at the Physionet Challenge 2013. 

PMID- 25069770
TI  - Field clinical study evaluating the efficacy and safety of an oral formulation
      containing milbemycin oxime/praziquantel (Milbemax(r), Novartis Animal Health) in
      the chemoprevention of the zoonotic canine infection by Dirofilaria repens.
AB  - BACKGROUND: Dirofilaria repens is the causative agent of subcutaneous
      dirofilariosis of dogs, other animals and humans. This nematode is transmitted by
      mosquitoes of Aedes, Anopheles and Culex genera. In dogs, the parasite may cause
      subclinical infection or cutaneous signs. Recently, D. repens has emerged and
      spread in different geographical areas, with an increase of cases in dogs and
      humans. Chemoprevention in dogs in endemic areas is the most reliable approach
      for controlling this infection. This paper describes a randomized, blocked and
      multicentric clinical field study investigating the efficacy of an oral, chewable
      formulation containing milbemycin oxime/praziquantel (Milbemax(r), Novartis
      Animal Health) in the chemoprevention of subcutaneous dirofilariosis in dogs.
      METHODS: This study was conducted in endemic areas of Italy. A total of 249 dogs,
      at two sites, negative for D. repens, were allocated into two groups (i.e.
      Treated -T1 vs Untreated-T2) with a ratio of 1:1, and subjected to clinical
      visits and blood sampling once monthly until the end of the study. All blood
      samples were microscopically and genetically examined. Animals belonging to T1
      group received a minimum target dose of 0.5 mg/kg bodyweight of milbemycin oxime
      and 5 mg/kg of praziquantel in commercial tablets (Milbemax(r)) according body
      weight once every 4 weeks. Animals of group T2 were not treated with Milbemax(r)
      but received, when necessary, specific parasiticide treatments. The study
      duration was 336 +/- 2 days for each dog. RESULTS: A total of 219 dogs completed
      the study (i.e. 111 in T1 and 108 in T2), while 30 dogs (i.e. 13 in T1, 17 in T2)
      were withdrawn for a variety of reasons unrelated to administration of
      Milbemax(r). The percentages of animals not showing microfilariae of D. repens
      were 100% (111 animals) in T1 and 94.7% (108 animals out of 114) in group T2.
      Milbemax(r) was shown to be safe in treated dogs. CONCLUSIONS: The results of
      this study confirm that the monthly use of Milbemax(r) in dogs is effective and
      safe for the prevention of subcutaneous dirofilariosis in endemic areas.

PMID- 25069771
TI  - Organic polymorphs: one-compound-based crystals with molecular-conformation- and
      packing-dependent luminescent properties.
AB  - The present study of structure-property relationships and disclosure of
      fascinating amplified spontaneous emission (ASE) behavior of an organic molecule
      not only exhibits the individual effect of molecular conformation and arrangement
      on the emission properties of the crystal separately, but also indicates that
      some concealed elegant properties of organic solids can be achieved through
      manipulating the polymorphic form. 

PMID- 25069773
TI  - Retraction: 'A cell cycle regulatory network controlling NF-kappaB subunit
      activity and function'.

PMID- 25069772
TI  - Genome-wide identification of miR-200 targets reveals a regulatory network
      controlling cell invasion.
AB  - The microRNAs of the miR-200 family maintain the central characteristics of
      epithelia and inhibit tumor cell motility and invasiveness. Using the Ago-HITS
      CLIP technology for transcriptome-wide identification of direct microRNA targets
      in living cells, along with extensive validation to verify the reliability of the
      approach, we have identified hundreds of miR-200a and miR-200b targets, providing
      insights into general features of miRNA target site selection. Gene ontology
      analysis revealed a predominant effect of miR-200 targets in widespread
      coordinate control of actin cytoskeleton dynamics. Functional characterization of
      the miR-200 targets indicates that they constitute subnetworks that underlie the
      ability of cancer cells to migrate and invade, including coordinate effects on
      Rho-ROCK signaling, invadopodia formation, MMP activity, and focal adhesions.
      Thus, the miR-200 family maintains the central characteristics of the epithelial
      phenotype by acting on numerous targets at multiple levels, encompassing both
      cytoskeletal effectors that control actin filament organization and dynamics, and
      upstream signals that locally regulate the cytoskeleton to maintain cell
      morphology and prevent cell migration. 

PMID- 25069774
TI  - What is the optimal pharmacological management of retained placenta?

PMID- 25069775
TI  - ROCK Inhibition Extends Passage of Pluripotent Stem Cell-Derived Retinal
      Pigmented Epithelium.
AB  - Human embryonic stem cells (hESCs) offer a potentially unlimited supply of cells
      for emerging cell-based therapies. Unfortunately, the process of deriving
      distinct cell types can be time consuming and expensive. In the developed world,
      age-related macular degeneration (AMD) is the leading cause of blindness in the
      elderly, with more than 7.2 million people afflicted in the U.S. alone. Both hESC
      derived retinal pigmented epithelium (hESC-RPE) and induced pluripotent stem cell
      derived RPE (iPSC-RPE) are being developed for AMD therapies by multiple groups,
      but their potential for expansion in culture is limited. To attempt to overcome
      this passage limitation, we examined the involvement of Rho-associated, coiled
      coil protein kinase (ROCK) in hESC-RPE and iPSC-RPE culture. We report that
      inhibiting ROCK1/2 with Y-27632 allows extended passage of hESC-RPE and iPSC-RPE.
      Microarray analysis suggests that ROCK inhibition could be suppressing an
      epithelial-to-mesenchymal transition through various pathways. These include
      inhibition of key ligands of the transforming growth factor-beta pathway (TGFB1
      and GDF6) and Wnt signaling. Two important processes are affected, allowing for
      an increase in hESC-RPE expansion. First, ROCK inhibition promotes proliferation
      by inducing multiple components that are involved in cell cycle progression.
      Second, ROCK inhibition affects many pathways that could be converging to
      suppress RPE-to-mesenchymal transition. This allows hESC-RPE to remain functional
      for an extended but finite period in culture. 

PMID- 25069776
TI  - Overexpression of polysialylated neural cell adhesion molecule improves the
      migration capacity of induced pluripotent stem cell-derived oligodendrocyte
      precursors.
AB  - Cell replacement therapy aiming at the compensation of lost oligodendrocytes and
      restoration of myelination in acquired or congenital demyelination disorders has
      gained considerable interest since the discovery of induced pluripotent stem
      cells (iPSCs). Patient-derived iPSCs provide an inexhaustible source for
      transplantable autologous oligodendrocyte precursors (OPCs). The first
      transplantation studies in animal models for demyelination with iPSC-derived OPCs
      demonstrated their survival and remyelinating capacity, but also revealed their
      limited migration capacity. In the present study, we induced overexpression of
      the polysialylating enzyme sialyltransferase X (STX) in iPSC-derived OPCs to
      stimulate the production of polysialic acid-neuronal cell adhesion molecules (PSA
      NCAMs), known to promote and facilitate the migration of OPCs. The STX
      overexpressing iPSC-derived OPCs showed a normal differentiation and maturation
      pattern and were able to downregulate PSA-NCAMs when they became myelin-forming
      oligodendrocytes. After implantation in the demyelinated corpus callosum of
      cuprizone-fed mice, STX-expressing iPSC-derived OPCs demonstrated a significant
      increase in migration along the axons. Our findings suggest that the reach and
      efficacy of iPSC-derived OPC transplantation can be improved by stimulating the
      OPC migration potential via specific gene modulation. 

PMID- 25069778
TI  - Glycerol as suitable solvent for the synthesis of metallic species and catalysis.
AB  - This Minireview considers the foremost reported works involving glycerol as a
      solvent in the synthesis of organometallic complexes and metallic nanoparticles.
      This analysis highlights their catalytic applications. A special emphasis is
      devoted to the ability of glycerol to immobilize nanometric species, which, in
      turn, enables an efficient recycling of the catalytic phase to give metal-free
      organic products. 

PMID- 25069777
TI  - Differentiation of human limbal-derived induced pluripotent stem cells into
      limbal-like epithelium.
AB  - Limbal epithelial stem cell (LESC) deficiency (LSCD) leads to corneal
      abnormalities resulting in compromised vision and blindness. LSCD can be
      potentially treated by transplantation of appropriate cells, which should be
      easily expandable and bankable. Induced pluripotent stem cells (iPSCs) are a
      promising source of transplantable LESCs. The purpose of this study was to
      generate human iPSCs and direct them to limbal differentiation by maintaining
      them on natural substrata mimicking the native LESC niche, including feederless
      denuded human amniotic membrane (HAM) and de-epithelialized corneas. These iPSCs
      were generated with nonintegrating vectors from human primary limbal epithelial
      cells. This choice of parent cells was supposed to enhance limbal cell
      differentiation from iPSCs by partial retention of parental epigenetic signatures
      in iPSCs. When the gene methylation patterns were compared in iPSCs to parental
      LESCs using Illumina global methylation arrays, limbal-derived iPSCs had fewer
      unique methylation changes than fibroblast-derived iPSCs, suggesting retention of
      epigenetic memory during reprogramming. Limbal iPSCs cultured for 2 weeks on HAM
      developed markedly higher expression of putative LESC markers ABCG2,
      DeltaNp63alpha, keratins 14, 15, and 17, N-cadherin, and TrkA than did fibroblast
      iPSCs. On HAM culture, the methylation profiles of select limbal iPSC genes
      (including NTRK1, coding for TrkA protein) became closer to the parental cells,
      but fibroblast iPSCs remained closer to parental fibroblasts. On denuded air
      lifted corneas, limbal iPSCs even upregulated differentiated corneal keratins 3
      and 12. These data emphasize the importance of the natural niche and limbal
      tissue of origin in generating iPSCs as a LESC source with translational
      potential for LSCD treatment. 

PMID- 25069780
TI  - Effects of fresh gas flow, tidal volume, and charcoal filters on the washout of
      sevoflurane from the Datex Ohmeda (GE) Aisys, Aestiva/5, and Excel 210 SE
      Anesthesia Workstations.
AB  - PURPOSE: We investigated the effects of tidal volume (VT), fresh gas flow (FGF),
      and a charcoal filter in the inspiratory limb on the washout of sevoflurane from
      the following Datex Ohmeda (GE) Anesthesia Workstations (AWSs): Aisys, Aestiva/5,
      and Excel 210SE. METHODS: After equilibrating the AWSs with 2% sevoflurane, the
      anesthetic was discontinued, and the absorbent anesthesia breathing circuit
      (ABC), reservoir bag, and test lung were changed. The lung was ventilated with
      350 or 200 mL.breath(-1), 15 breaths.min(-1), and a FGF of 10 L.min(-1) while the
      washout of sevoflurane was performed in triplicate using a calibrated Datex
      Ohmeda Capnomac UltimaTM and a calibrated MIRAN SapphIRe XL ambient air analyzer
      until the concentration was <= 10 parts per million (ppm). The effects of
      decreasing the FGF to 5 and 2 L.min(-1) after the initial washout and of a
      charcoal filter in the ABC were recorded separately. RESULTS: The median washout
      times with the Aisys AWS (14 min, P < 0.01) and the Aestiva/5 (17 min, P < 0.001)
      with VT 350 mL.breath(-1) were significantly less than that with the Excel 210SE
      (32 min). The mean (95% confidence interval) washout time with the Aisys
      increased to 23.5 (21.5 to 25.5) min with VT 200 mL.breath(-1) (P < 0.01).
      Decreasing the FGF from 10 to 5 and 2 L.min(-1) with the Aisys caused a rebound
      in sevoflurane concentration to >= 50 ppm. Placement of a charcoal filter in the
      inspiratory limb reduced the sevoflurane concentration to < 2 ppm in the Aisys
      and Aestiva/5 AWSs within two minutes. CONCLUSION: The GE AWSs should be purged
      with large FGFs and VTs ~350 mL.breath(-1) for ~25 min to achieve 10 ppm
      sevoflurane. The FGF should be maintained to avoid a rebound in anesthetic
      concentration. Charcoal filters rapidly decrease the anesthetic concentration to
      < 2 ppm.

PMID- 25069779
TI  - A genomic analysis of mouse models of breast cancer reveals molecular features of
      mouse models and relationships to human breast cancer.
AB  - INTRODUCTION: Genomic variability limits the efficacy of breast cancer therapy.
      To simplify the study of the molecular complexity of breast cancer, researchers
      have used mouse mammary tumor models. However, the degree to which mouse models
      model human breast cancer and are reflective of the human heterogeneity has yet
      to be demonstrated with gene expression studies on a large scale. METHODS: To
      this end, we have built a database consisting of 1,172 mouse mammary tumor
      samples from 26 different major oncogenic mouse mammary tumor models. RESULTS: In
      this dataset we identified heterogeneity within mouse models and noted a
      surprising amount of interrelatedness between models, despite differences in the
      tumor initiating oncogene. Making comparisons between models, we identified
      differentially expressed genes with alteration correlating with initiating events
      in each model. Using annotation tools, we identified transcription factors with a
      high likelihood of activity within these models. Gene signatures predicted
      activation of major cell signaling pathways in each model, predictions that
      correlated with previous genetic studies. Finally, we noted relationships between
      mouse models and human breast cancer at both the level of gene expression and
      predicted signal pathway activity. Importantly, we identified individual mouse
      models that recapitulate human breast cancer heterogeneity at the level of gene
      expression. CONCLUSIONS: This work underscores the importance of fully
      characterizing mouse tumor biology at molecular, histological and genomic levels
      before a valid comparison to human breast cancer may be drawn and provides an
      important bioinformatic resource.

PMID- 25069781
TI  - Effectiveness of using high-fidelity simulation to teach the management of
      general anesthesia for Cesarean delivery.
AB  - PURPOSE: The objective of this study was to assess the influence of a teaching
      plan consisting of didactic teaching and repeated simulations on the performance
      of anesthesia residents in the management of general anesthesia (GA) for
      emergency Cesarean delivery (CD). METHODS: Twenty-one postgraduate year 2 (PGY2)
      and 3 (PGY3) anesthesia residents from the University of Toronto were recruited
      in this prospective cohort study. All participants received didactic teaching in
      the management of GA for emergency CD, which was followed one week later by
      assessment of performance in the same scenario using a high-fidelity simulator.
      Another simulation assessment was repeated two months later in the same scenario.
      All simulation video recordings were assessed by two blinded experts using a
      validated checklist and an Anaesthetists' Non-Technical Skills (ANTS) scale in
      order to rate their technical and non-technical skills, respectively. The
      participants' performance (based on the above scales) in the two simulation
      sessions were then compared. RESULTS: Nineteen residents completed both
      simulation sessions. There was an improvement in the mean (SD) weighted checklist
      score from 64.5% (7.1%) in session 1 to 76.7% (6.7%) in session 2 (P < 0.001).
      The mean (SD) ANTS scores also increased from 2.8 (0.5) in session 1 to 3.3 (0.4)
      in session 2 (P = 0.001). No difference in the checklist or ANTS scores was seen
      between PGY2 and PGY3 residents in any of the simulation sessions. Several common
      performance errors were identified, but these improved in the second session. The
      correlation between checklist and ANTS scores was moderately high (correlation
      coefficient [r] = 0.7; P < 0.001). The inter-rater reliability among the experts
      was also high (intraclass correlation coefficient [ICC] for the checklist = 0.72;
      95% confidence interval [CI] 0.62 to 0.81; ICC for the ANTS = 0.74; 95% CI 0.49
      to 0.89). CONCLUSION: Didactic teaching followed by simulation sessions enhances
      not only the technical skills but also the non-technical skills of residents,
      most likely due to the feedback received after the first simulation session.
      Repeated simulation sessions may help prepare residents to deal more effectively
      with similar critical situations in clinical practice with minimum errors.

PMID- 25069782
TI  - Sevoflurane therapy for life-threatening acute severe asthma: a case report.
AB  - INTRODUCTION: Acute severe asthma is a life-threatening form of bronchial
      constriction in which the progressively worsening airway obstruction is
      unresponsive to the usual appropriate bronchodilator therapy. Pathophysiological
      changes restrict airflow, which leads to premature closure of the airway on
      expiration, impaired gas exchange, and dynamic hyperinflation ("air-trapping").
      Additionally, patients suffering from asthma for a prolonged period of time
      usually have serious comorbidities. These conditions constitute a challenge
      during the treatment of this disease. Therapeutic interventions are designed to
      reduce airway resistance and improve respiratory status. To achieve therapeutic
      goals, appropriate bronchodilator treatment is indispensable, and mechanical
      ventilation under adequate sedation may also be required. The volatile anesthetic
      agent, sevoflurane, meets both criteria; therefore, its use can be beneficial and
      should be considered. CASE PRESENTATION: A 67-yr-old Caucasian male presented
      with acute life-threatening asthma provoked by an assumed upper airway infection
      and non-steroidal anti-inflammatory drug antipyretics, complicated by chronic
      atrial fibrillation and hemodynamic instability. Due to frequent premature
      ventricular contractions, conventional treatment was considered unsafe and
      discontinued, and sevoflurane inhalation was initiated via the AnaConDa
      (Anaesthetic Conserving Device). Symptoms of life-threatening bronchospasm
      resolved, and the patient's respiratory status improved within hours. Adequate
      sedation was also achieved without any hemodynamic adverse effects. CONCLUSION:
      The volatile anesthetic agent, sevoflurane, is used widely in anesthesia
      practice. Its utility for treatment of refractory bronchospasm has been
      appreciated for years; however, its administration was difficult within the
      environment of the intensive care unit due to the need for an anesthesia machine
      and a scavenging system. The introduction of the AnaConDa eliminates these
      obstacles and makes the use of sevoflurane safe and simple. Our case report
      reveals the potential of sevoflurane as a "two-in-one" (bronchodilator and
      sedative) drug to treat a severe acute asthma attack.

PMID- 25069783
TI  - Specific mesothelial signature marks the heterogeneity of mesenchymal stem cells
      from high-grade serous ovarian cancer.
AB  - Mesenchymal stem/stromal cells (MSCs) are the precursors of various cell types
      that compose both normal and cancer tissue microenvironments. In order to support
      the widely diversified parenchymal cells and tissue organization, MSCs are
      characterized by a large degree of heterogeneity, although available analyses of
      molecular and transcriptional data do not provide clear evidence. We have
      isolated MSCs from high-grade serous ovarian cancers (HG-SOCs) and various normal
      tissues (N-MSCs), demonstrated their normal genotype and analyzed their
      transcriptional activity with respect to the large comprehensive FANTOM5 sample
      dataset. Our integrative analysis conducted against the extensive panel of
      primary cells and tissues of the FANTOM5 project allowed us to mark the HG-SOC
      MSCs CAGE-seq transcriptional heterogeneity and to identify a cell-type-specific
      transcriptional activity showing a significant relationship with primary
      mesothelial cells. Our analysis shows that MSCs isolated from different tissues
      are highly heterogeneous. The mesothelial-related gene signature identified in
      this study supports the hypothesis that HG-SOC-MSCs are bona fide representatives
      of the ovarian district. This finding indicates that HG-SOC-MSCs could actually
      derive from the coelomic mesothelium, suggesting that they might be linked to the
      epithelial tumor through common embryological precursors.

PMID- 25069784
TI  - Remodeled ostial atherosclerotic plaque in a single coronary artery demonstrated
      by computed tomography coronary angiography.

PMID- 25069785
TI  - REHAL(r), a telemedicine platform for home cardiac rehabilitation.
AB  - AIM: The new REHAL(r) platform manages home-based cardiac rehabilitation programs
      without most of the drawbacks of an earlier E-Remedy EC proposal. The proposal is
      based on the awareness that safe home rehabilitation is only possible in the post
      hospital phase when the patient no longer needs direct control by medical staff
      and has become accustomed to the technological set-up. METHODS: The platform is
      composed of a web-based database and client software (Ergomonitor), which allows
      health staff to manage the sessions without a real-time connection and legal
      liability. Ergomonitor permits the complete management of a bike (training
      session settings, web transmission and data recording) by a serial connection to
      a PC. Patients own their data and may approve the access of health personnel to
      evaluate the results and introduce longitudinal ambulatory information together
      with updated physical activity protocols. The health service does not bear the
      cost of the technological set-up. Ergomonitor acquires and records heart rate,
      loads, pedalling speed and other parameters of interest (i.e., arterial pressure)
      and forwards data to a remote database. Health personnel can modify time by time
      the scheduled exercise settings, analyse the results of each session and compare
      session by session. RESULTS: The platform is actually used in hospital, gymnasium
      and home context. More than 1000 subjects have been enrolled in the protocol,
      with a very good appreciation. CONCLUSION: The first experience of REHAL(r) (six
      months, more than 1000 enrolled patients) highlights the positive aspects of the
      solution: the patients are very satisfied with the continuity of the
      rehabilitation programme and the clinicians are very satisfied they can follow
      their patient population longitudinally and with a personalized protocol.

PMID- 25069786
TI  - Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and
      smoked administration: a comparative study.
AB  - N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays
      partial agonist activity at the 5-HT2A receptor and induces intense psychedelic
      effects in humans when administered parenterally. However, self-administration
      studies have reported a total lack of activity following oral intake. This is
      thought to be due to extensive degradation by monoamine oxidase (MAO). Despite
      increased use of DMT and DMT-containing preparations, such as the plant tea
      ayahuasca, the biotransformation of DMT in humans when administered alone is
      relatively unknown. Here we used high performance liquid chromatography
      (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem
      mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral
      and smoked DMT. Twenty-four-hour urine samples were obtained from 6 DMT users
      before and after intake of 25 mg DMT doses on two separate sessions. In one
      session, DMT was taken orally and in another it was smoked. After oral ingestion,
      no psychotropic effects were experienced and no DMT was recovered in urine. MAO
      dependent indole-3-acetic acid (IAA) represented 97% of the recovered compounds,
      whereas DMT-N-oxide (DMT-NO) accounted for only 3%. When the smoked route was
      used, the drug was fully psychoactive, unmetabolized DMT and DMT-NO rose to 10%
      and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was
      found between the IAA/DMT-NO ratio and subjective effects scores. These findings
      show that in the smoked route a shift from the highly efficient MAO-dependent to
      the less efficient CYP-dependent metabolism takes place. This shift leads to
      psychoactivity and is analogous to that observed in ayahuasca preparations
      combining DMT with MAO inhibitors.

PMID- 25069787
TI  - Stochastic neural field equations: a rigorous footing.
AB  - We here consider a stochastic version of the classical neural field equation that
      is currently actively studied in the mathematical neuroscience community. Our
      goal is to present a well-known rigorous probabilistic framework in which to
      study these equations in a way that is accessible to practitioners currently
      working in the area, and thus to bridge some of the cultural/scientific gaps
      between probability theory and mathematical biology. In this way, the paper is
      intended to act as a reference that collects together relevant rigorous results
      about notions of solutions and well-posedness, which although may be
      straightforward to experts from SPDEs, are largely unknown in the neuroscientific
      community, and difficult to find in a very large body of literature. Moreover, in
      the course of our study we provide some new specific conditions on the parameters
      appearing in the equation (in particular on the neural field kernel) that
      guarantee the existence of a solution. 

PMID- 25069788
TI  - Cadmium induces urokinase-type plasminogen activator receptor expression and the
      cell invasiveness of human gastric cancer cells via the ERK-1/2, NF-kappaB, and
      AP-1 signaling pathways.
AB  - Cadmium exposure has been linked to human cancers, including stomach cancer. In
      this study, the effects of cadmium on urokinase-type plasminogen activator
      receptor (uPAR) expression in human gastric cancer cells and the underlying
      signal transduction pathways were investigated. Cadmium induced uPAR expression
      in a time- and concentration-dependent manner. Cadmium also induced uPAR promoter
      activity. Additionally, cadmium induced the activation of extracellular signal
      regulated kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and
      the activation of c-Jun amino terminal kinase (JNK). A specific inhibitor of MEK
      1 (PD98059) inhibited cadmium-induced uPAR expression, while JNK and p38 MAPK
      inhibitors did not. Expression vectors encoding dominant-negative MEK-1 (pMCL
      K97M) also prevented cadmium-induced uPAR promoter activity. Site-directed
      mutagenesis and electrophoretic mobility shift studies showed that sites for the
      transcription factors nuclear factor (NF)-kappaB and activator protein-1 (AP-1)
      were involved in cadmium-induced uPAR transcription. Suppression of the cadmium
      induced uPAR promoter activity by a mutated-type NF-kappaB-inducing kinase and I
      kappaB and an AP-1 decoy oligonucleotide confirmed that the activation of NF
      kappaB and AP-1 are essential for cadmium-induced uPAR upregulation. Cells
      pretreated with cadmium showed markedly enhanced invasiveness and this effect was
      partially abrogated by uPAR-neutralizing antibodies and by inhibitors of ERK-1/2,
      NF-kappaB, and AP-1. These results suggest that cadmium induces uPAR expression
      via ERK-1/2, NF-kappaB, and AP-1 signaling pathways and, in turn, stimulates cell
      invasiveness in human gastric cancer AGS cells. 

PMID- 25069789
TI  - Effect of and satisfaction with www.elearnSCI.org for training of nurse students:
      a submodule pilot study.
AB  - STUDY DESIGN: Interventional training session. OBJECTIVE: To investigate the
      effect and satisfaction with didactic training using printed text of a submodule
      of www.elearnSCI.org for nurse students and to assess the answers of each
      question. SETTING: A Peking University teaching hospital. METHODS: Twenty-eight
      nurse students in two groups (14 in each) were involved. Only group A received a
      translated print-out of the slides from the 'Nursing management' submodule in
      www.elearnSCI.org for 1-h self-study before the class. At the beginning of class,
      both groups were tested using the self assessment questions. Then, a lecture
      according to the content of this submodule was carried out and afterwards both
      groups answered the self assessment questions again. Finally, both groups filled
      in a training course satisfaction questionnaire. RESULTS: At the beginning of the
      class, the mean score (max 9) of the self assessment in group A was 7.1 +/- 1.1,
      which was significantly higher than that in group B (4.9 +/- 1.7, P = 0.001).
      After the lecture, the mean score of the self assessment in group A had
      insignificantly increased to 7.4 +/- 1.3, whereas in group B it increased
      significantly to 6.9 +/- 0.8 (P < 0.001). The mean score (max 50) of the training
      course satisfaction questionnaire was 42.8 +/- 5.2. Sixty-four percentage of the
      students indicated that they were very satisfied (overall score ? 42) with the
      training and no students were unsatisfied (overall score < 30). CONCLUSION: Self
      study and lecture presentation are effective methods for training the content of
      www.elearnSCI.org to nurse students. The training satisfaction of this submodule
      within the www.elearnSCI.org is favorable.

PMID- 25069790
TI  - Mechanical comparison of 3 anchoring techniques in the muscular process for
      laryngoplasty in the equine larynx.
AB  - OBJECTIVE: To compare mechanical properties of 2 techniques with a conventional
      technique for anchoring the muscular process in a laryngoplasty procedure. STUDY
      DESIGN: Experimental ex vivo study. SAMPLE POPULATION: Equine larynges (n = 60).
      METHODS: A single loop (SL), a screw (SC), and a double loop technique (DL) were
      compared. Constructs were subjected to cyclic loading, oscillating from 5 to 50 N
      for 3000 cycles, followed by a single cycle to failure test. Mean distraction,
      load at failure, stiffness, and failure mode were compared between groups.
      RESULTS: Mean +/- SD distraction in cyclic loading was greater for DL (2.1 +/-
      0.7 mm) than for SL (1.9 +/- 1.3 mm) and SC (1.539 +/- 0.9 mm); however, there
      was no significant difference between SL and SC or between SL and DL. Mean
      ultimate failure load was greater for DL (240 +/- 44.56 N) than for SC (189.59 +/
      46.16 N) and SL (150.93 +/- 44.43 N) and greater for SC compared with SL.
      Failure occurred by cartilage tearing for DL and SL, and by screw pull out (n =
      13) or knot slippage (4) for SC. CONCLUSION: In cyclic loading, SC is more stable
      than DL and at least as stable as SL. In single cycle to failure, DL is the
      strongest construct and SC is stronger than SL.

PMID- 25069791
TI  - The relationship of serum cortisol levels with depression, cognitive function and
      sleep disorders in chronic kidney disease and hemodialysis patients.
AB  - In the present study, the relationships between cortisol, cognitive function,
      depressive behavior, and sleep quality in chronic kidney disease (CKD) and
      hemodialysis (HD) patients was investigated. Patients underwent history taking,
      physical examination, biochemical analysis, 24-h urine collection (for CKD
      patients only), measurement of dialysis adequacy (for HD patients only),
      evaluation of cognitive function, depressive behavior and sleep quality. Among
      study participants 58 had creatinine clearance >=60 mL/min/1.73 m(2) (Group 1),
      41 had creatinine clearance between 30 and 59 mL/min/1.73 m(2) (Group 2), 25 had
      creatinine clearance between 15 and 29 mL/min/1.73 m(2) (Group 3) and 12 had
      creatinine clearance <15 mL/min/1.73 m(2) (Group 4). 38 patients were regular HD
      patients (Group 5). The cortisol levels in Group 1, 2, 3, 4 and 5 patients were
      472.3 +/- 138.4, 490.2 +/- 214.3, 541.6 +/- 172.8, 569.9 +/- 101.0 and 637.8 +/-
      153.7 nmol/L, respectively (P < 0.0001 for trend). In both non-dialysis patient
      group and dialysis patients linear regression analysis showed that cortisol was
      independently related with Beck depression inventory (BDI) score (P: 0.013 and
      0.001, respectively) but not with cognitive function and sleep quality. In
      conclusion serum cortisol levels were independently associated with depressive
      behavior both in CKD and HD patients but not with cognitive function and sleep
      quality.

PMID- 25069792
TI  - Von Hippel-Lindau disease type 2 in a Chinese family with a VHL p.W88X
      truncation.
AB  - Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by
      germline mutations in the synonymous VHL gene encoding a tumor suppressor.
      Affected individuals are susceptible to various benign and malignant tumors.
      Based on the phenotypes, VHL disease is classified as type 1 and type 2. Here, we
      describe a Chinese family diagnosed as VHL disease type 2, with different
      metabolic status of tumors on FDG PET-CT. Genetic analysis revealed a germline
      c.264G>A point mutation, resulting in premature termination at codon 88 (p.W88X).
      This pedigree represents a rare link between p.W88X nonsense mutation (genotype)
      and VHL disease type 2 (phenotype), which has not been previously described. This
      is also the first nonsense mutation to manifest as VHL disease type 2 in ethnic
      Chinese. We also reviewed the literature and provided an outline of mutations
      associated with VHL disease in China.

PMID- 25069793
TI  - Identification of prognostic inflammatory factors in colorectal liver metastases.
AB  - BACKGROUND: The modified Glasgow Prognostic Score (mGPS) has been reported to be
      an important prognostic indicator in a number of tumor types, including
      colorectal cancer (CRC). The features of the inflammatory state thought to
      accompany elevated C-reactive protein (CRP), a key feature of mGPS, were
      characterized in patients with colorectal liver metastases. Additional
      inflammatory mediators that contribute to prognosis were explored. METHODS: In
      sera from 69 patients with colorectal liver metastases, a panel of 42
      inflammatory mediators were quantified as a function of CRP levels, and as a
      function of disease-free survival. Multivariate statistical methods were used to
      determine association of each mediator with elevated CRP and truncated disease
      free survival. RESULTS: Elevated CRP was confirmed to be a strong predictor of
      survival (HR 4.00, p = 0.001) and recurrence (HR 3.30, p = 0.002). The
      inflammatory state associated with elevated CRP was comprised of raised IL-1beta,
      IL-6, IL-12 and IL-15. In addition, elevated IL-8 and PDGF-AB/BB and decreased
      eotaxin and IP-10 were associated with worse disease-free and overall survival.
      CONCLUSIONS: Elevated CRP is associated with a proinflammatory state. The
      inflammatory state is an important prognostic indicator in CRC liver metastases.
      The individual contributions of tumor biology and the host to this inflammatory
      response will require further investigation.

PMID- 25069795
TI  - Health policy basics: the Physician Payment Sunshine Act and the Open Payments
      program.
AB  - The Open Payments program is a government initiative through which financial
      relationships between applicable industries and covered physicians or teaching
      hospitals are publicly reported. The program does not assess these relationships
      but rather facilitates transparency and allows stakeholders to use this
      information in making informed decisions. This article outlines the program and
      its goals, reviews its requirements and when they go into effect, examines the
      implications for physicians and their patients, and makes recommendations to help
      physicians and teaching hospitals prepare for its implementation. 

PMID- 25069794
TI  - Dynamic nuclear polarization of (1)H, (13)C, and (59)Co in a
      tris(ethylenediamine)cobalt(III) crystalline lattice doped with Cr(III).
AB  - The study of inorganic crystalline materials by solid-state NMR spectroscopy is
      often complicated by the low sensitivity of heavy nuclei. However, these
      materials often contain or can be prepared with paramagnetic dopants without
      significantly affecting the structure of the crystalline host. Dynamic nuclear
      polarization (DNP) is generally capable of enhancing NMR signals by transferring
      the magnetization of unpaired electrons to the nuclei. Therefore, the NMR
      sensitivity in these paramagnetically doped crystals might be increased by DNP.
      In this paper we demonstrate the possibility of efficient DNP transfer in
      polycrystalline samples of [Co(en)3Cl3]2.NaCl.6H2O (en = ethylenediamine, C2H8N2)
      doped with Cr(III) in varying concentrations between 0.1 and 3 mol %. We
      demonstrate that (1)H, (13)C, and (59)Co can be polarized by irradiation of
      Cr(III) with 140 GHz microwaves at a magnetic field of 5 T. We further explain
      our findings on the basis of electron paramagnetic resonance spectroscopy of the
      Cr(III) site and analysis of its temperature-dependent zero-field splitting, as
      well as the dependence of the DNP enhancement factor on the external magnetic
      field and microwave power. This first demonstration of DNP transfer from one
      paramagnetic metal ion to its diamagnetic host metal ion will pave the way for
      future applications of DNP in paramagnetically doped materials or
      metalloproteins. 

PMID- 25069796
TI  - Oxovanadium(IV) complexes of curcumin for cellular imaging and mitochondria
      targeted photocytotoxicity.
AB  - Oxovanadium(IV) complexes [VO(R-tpy)(cur)](ClO4) (1, 2) of curcumin (Hcur) and
      terpyridine ligands (R-tpy) where R is phenyl (phtpy in 1) or p
      triphenylphosphonium methylphenyl bromide (C6H4CH2PPh3Br) (TPP-phtpy in 2) were
      prepared and characterized and their DNA photocleavage activity,
      photocytotoxicity and cellular localization in cancer cells (HeLa and MCF-7) were
      studied. Acetylacetonate (acac) complexes [VO(R-tpy)(acac)](ClO4) of phtpy (3)
      and TPP-phtpy (4) were prepared and used as the control species. These complexes
      showed efficient cleavage of pUC19 DNA in visible light of 454 nm and near-IR
      light of 705 nm. Complexes 1 and 2 showed significant photocytotoxicity in
      visible light of 400-700 nm. FACS analysis showed sub-G1/G0 phase cell-cycle
      arrest in cancer cells when treated with 1 and 2 in visible light in comparison
      with the dark controls. Fluorescence microscopic studies revealed specific
      localization of the p-triphenylphosphonium complex 2 in the mitochondria of MCF-7
      cancer cells whereas no such specificity was observed for complex 1.

PMID- 25069797
TI  - Progression-free survival remains poor over sequential lines of systemic therapy
      in patients with BRAF-mutated colorectal cancer.
AB  - BACKGROUND: BRAF mutations occur in 5% to 10% of metastatic colorectal cancers
      and are biomarkers associated with a poor prognosis. However, the outcomes with
      standard chemotherapy over sequential lines of therapy in a large cohort of
      patients with BRAF-mutant tumors have not been described. PATIENTS AND METHODS:
      We searched the M.D. Anderson Cancer Center databases for patients with
      colorectal cancer and identified BRAF mutations between December 2003 and May
      2012. Patients were analyzed for clinical characteristics, PFS, overall survival,
      and chemotherapeutic agents used. Survival was estimated according to the Kaplan
      Meier method. RESULTS: Among the 1567 patients tested for BRAF mutations at our
      institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who
      presented with metastatic disease received a median of 2 lines of chemotherapy.
      For the first 3 lines of chemotherapy, median PFS was 6.3 months (n = 69
      patients; 95% confidence interval [CI], 4.9-7.7 months), 2.5 months (n = 58
      patients; 95% CI, 1.8-3.0 months), and 2.6 months (n = 31 patients; 95% CI, 1.0
      4.2 months), respectively. Median PFS was not affected by the backbone
      chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or
      irinotecan-based (6.4 months vs. 5.4 months, respectively; P = .99). CONCLUSION:
      PFS is expectedly poor for patients with BRAF-mutated metastatic colorectal
      cancer. Despite the ascertainment bias present (with testing preferentially
      performed in patients suitable for clinical trials in refractory disease), these
      data provide historic controls suitable for future study design and support the
      idea that novel therapeutic options are essential in this population.

PMID- 25069798
TI  - Evaluation of the pharmacokinetic interaction between ticagrelor and venlafaxine,
      a cytochrome P-450 2D6 substrate, in healthy subjects.
AB  - PURPOSE: Ticagrelor is a reversibly binding P2Y12 receptor antagonist used
      clinically for the prevention of atherothrombotic events in patients with acute
      coronary syndromes (ACS). Ticagrelor has been shown in vitro to be a weak
      inhibitor of cytochrome P-450 (CYP) 2D6, a clinically important enzyme for the
      metabolism of many drugs. This study assessed the effects of coadministration of
      ticagrelor on the pharmacokinetics of the CYP2D6 substrate venlafaxine. The
      impact of venlafaxine on ticagrelor pharmacokinetic parameters was also
      investigated. METHODS: Healthy subjects (N = 22) received a single 180-mg oral
      dose of ticagrelor on days 1 and 9 and oral doses of venlafaxine on day 4 (37.5
      mg BID) and days 5 through 10 (75 mg BID). Plasma concentrations of ticagrelor,
      venlafaxine, and their metabolites (AR-C124910XX and O-desmethylvenlafaxine
      [ODV], respectively) were quantified for pharmacokinetic analyses. Safety and
      tolerability were assessed throughout the study. FINDINGS: Overall, 19 of 25
      subjects were male; 14 were white, 10 were black, and 1 was Asian. Mean (SD) age
      was 26 (6) years, and mean (SD) body mass index was 24.3 (2.9) kg/m(2).
      Ticagrelor had no effect on overall exposure to venlafaxine, as assessed by the
      AUC0-tau (geometric least squares mean ratio, 110.32 ng . h/mL [90% CI, 106.27
      114.52]). Venlafaxine Cmax was increased by 22% in the presence of ticagrelor
      (121.83 ng/mL [90% CI, 111.80-132.75]). ODV AUC0-tau and Cmax were unaffected by
      coadministration with ticagrelor (98.71 ng . h/mL [90% CI, 96.61-100.85] and
      101.44 ng/mL [90% CI, 98.34-104.65], respectively). Venlafaxine had no effect on
      the Cmax or AUC0-infinity of ticagrelor (96.54 ng/mL [90% CI, 85.03-109.61] and
      89.67 ng . h/mL [90% CI, 82.78-97.14]) or AR-C124910XX (106.39 ng/mL [90% CI,
      96.10-117.78] and 106.32 ng . h/mL [90% CI, 97.28-116.21], respectively).
      Ticagrelor and venlafaxine were well tolerated whether given alone or in
      combination. IMPLICATIONS: Ticagrelor had no clinically relevant effect on the
      plasma levels of venlafaxine and its CYP2D6-generated active metabolite, ODV. On
      the basis of these data, ticagrelor is not expected to affect CYP2D6-mediated
      drug metabolism to a clinically relevant extent. Venlafaxine had no effect on the
      pharmacokinetics of ticagrelor.

PMID- 25069799
TI  - Cost-minimization analysis of lanthanum carbonate versus sevelamer hydrochloride
      in US patients with end-stage renal disease.
AB  - PURPOSE: Sevelamer hydrochloride (SH) and lanthanum carbonate (LC) are calcium
      free phosphate binders used in the clinical management of hyperphosphatemia in
      patients with end-stage renal disease (ESRD). The objective of this analysis was
      to assess the cost-effectiveness of LC monotherapy compared with SH monotherapy
      in US patients with ESRD in a clinical practice setting. METHODS: This was a post
      hoc assessment of phosphate binder costs among US patients with ESRD who
      converted from SH to LC monotherapy in a previously published, 16-week, Phase IV,
      real-world study. Calculations of drug costs used both average wholesale price
      (AWP) and wholesale acquisition cost (WAC). FINDINGS: There were 953 patients
      with available baseline SH dose data; 950 also had a recorded LC dose >0 mg at
      baseline, and 691 had dose data available for both SH at baseline and LC at week
      16 (post hoc analysis population). Baseline demographic characteristics were
      similar in excluded patients and the post hoc analysis population. Mean (SD)
      serum phosphate levels were 5.91 (1.66) mg/dL at baseline and 5.93 (1.85) mg/dL
      after conversion to LC monotherapy for 16 weeks. Mean AWP costs were US$35.72
      (16.89) per day at baseline and US$24.69 (8.28) per day at week 16, yielding an
      overall mean cost change (defined as LC cost - SH cost) of -US$11.03 (16.37) per
      day in favor of LC. The overall mean WAC cost change was -US$9.17 (13.64) per
      day. Within baseline SH dose subgroups 2400 to 4800, >4800 to 7200, >7200 to
      9600, and >9600 mg/d, the mean AWP cost change ranged from US$2.78 (9.26) per day
      in favor of SH for the 2400- to 4800-mg/d subgroup to -US$33.15 (12.58) per day
      in favor of LC for the >9600-mg/d subgroup. Mean WAC cost changes showed a
      similar trend, ranging from US$2.33 (7.72) per day to -US$27.59 (10.48) per day.
      Linear regression analyses revealed that the inflection SH doses corresponding to
      a mean cost change of zero were 4905 mg/d (AWP) and 4908 mg/d (WAC). For the 455
      (66%) patients in the post hoc analysis population who had baseline SH doses at
      least as high (>= 5600 mg/d) as these point estimates, the mean SH:LC tablet
      ratio was >= 3.7, indicating a mean reduction in the tablet burden after
      conversion to LC of >= 73%. IMPLICATIONS: This real-world assessment of
      comparative phosphate binder drug costs between SH and LC among US patients with
      ESRD indicates that average cost savings with LC use increased with increasing SH
      doses. Conversion to LC from SH >= 5600 mg/d reduced drug costs and tablet burden
      while maintaining serum phosphate levels.

PMID- 25069800
TI  - Correlates of caring for the drinkers and others among those harmed by another's
      drinking.
AB  - INTRODUCTION AND AIMS: This study identifies the correlates of caring for harmful
      drinkers and others, and examines how caring for that person impacts on
      respondents' well-being and use of services. DESIGN AND METHODS: The study
      utilises the data from the 2008 Australian Alcohol Harm to Others Survey (n =
      2649), in which 778 respondents reported they were harmed because of the drinking
      of someone they knew. Respondents were asked about the person they were most
      adversely affected by and whether they spent time caring for this person because
      of their drinking. Logistic regression models are developed to examine which
      factors were associated with the prevalence of caring for others. RESULTS: The
      study reveals that the respondents who cared for others because of the other's
      drinking reported lower quality of life than the respondents who did not have to
      do this. The results of the logistic regression suggest that respondents were
      more likely to care for the drinker if the drinker drank more (as the usual
      quantity of alcohol consumed increased), but less likely to care for the drinker
      if the drinker drank five or more drinks on more than four days per week.
      DISCUSSION AND CONCLUSIONS: The findings of the study suggest that the drinking
      of family and friends can be a substantial burden for their households, families,
      friends and others. Policy approaches that reduce the amount of heavy drinking,
      particularly heavy drinking in a single occasion, are likely to reduce the burden
      of caring for others because of other's drinking.

PMID- 25069802
TI  - Physiologically based pharmacokinetic modeling of hydrogen cyanide levels in
      human breath.
AB  - Hydrogen cyanide (HCN) is a potent and fast-acting toxin increasingly recognized
      as an important cause of death in fire victims. Prompt diagnosis and treatment of
      cyanide poisoning are essential to avoid fatalities. Unfortunately, there are at
      present few rapid diagnostic methods. A noninvasive methodology would be to use
      HCN in exhaled air as a marker for systemic exposure. To explore this
      possibility, we developed a preliminary physiologically based pharmacokinetic
      model. The model suggests that breath HCN levels following inhalation exposure at
      near-lethal and lethal conditions are 0.1-1 ppm, i.e., one to two orders of
      magnitude higher than the background breath level of about 0.01 ppm in unexposed
      subjects. Hence, our results imply that breath analysis may be used as a rapid
      diagnostic method for cyanide poisoning. 

PMID- 25069801
TI  - Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive
      androstane receptor (CAR) activation and protects against acetaminophen- and
      amiodarone-induced cytotoxicity.
AB  - Antagonizing the action of the pregnane X receptor (PXR) may have important
      clinical implications for preventing inducer-drug interactions and improving
      therapeutic efficacy. We identified a widely distributed isothiocyanate, allyl
      isothiocyanate (AITC), which acts as an effective antagonist of the nuclear
      receptor pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor
      (CAR, NR1I3). HepG2 cells were used to assay reporter function, mRNA levels, and
      protein expression. Catalytic activities of the PXR and CAR target genes, CYP3A4
      and CYP2B6, respectively, were also assessed in differentiated HepaRG cells.
      Protective effects of AITC on rifampin-induced cytotoxicity were observed, and
      transient transfection assays showed that AITC was able to effectively attenuate
      the agonist effects of rifampin and CITCO on human PXR and CAR activity,
      respectively. AITC-mediated reduction in the transcriptional activity of PXR and
      CAR correlated well with the suppression of CYP3A4 and CYP2B6 expression in HepG2
      cells, which reflected the reduced catalytic activities of both of these genes
      following AITC treatment in differentiated HepaRG cells. Furthermore, AITC
      disrupts the co-regulations of PXR with several important co-regulators.
      Furthermore, the antagonist effect of AITC against PXR was found in HepaRG cells
      upon addition of acetaminophen (APAP) and amiodarone, indicating that AITC
      protects cells from drug-induced cytotoxicity. Taken together, our results show
      that AITC inhibits the transactivation effects of PXR and CAR and reduces the
      expression and function of CYP3A4 and CYP2B6. Additionally, AITC reversed the
      cytotoxic effects of APAP and amiodarone induced by PXR ligand. Results from this
      study suggest that AITC could be a powerful agent for reducing potentially
      dangerous interactions between transcriptional inducers of CYP enzymes and
      therapeutic drugs.

PMID- 25069803
TI  - Toxicogenomic effect of nickel and beyond.
AB  - Nickel is widely applied in industrial settings and Ni(II) compounds have been
      classified as group one human carcinogens. The molecular basis of Ni(II)
      carcinogenicity has proved complex, for many stress response pathways are
      activated and yield unexpected Ni(II)-specific toxicology profile. Ni(II)-induced
      toxicogenomic change has been associated with altered activity of HIF, p53, c
      MYC, NFkappaB and iron and 2-oxoglutarate-dependent dioxygenases. Advancing high
      throughput technology has indicated the toxicogenome of Ni(II) involves crosstalk
      between HIF, p53, c-MYC, NFkappaB and dioxygenases. This paper is intended to
      review the network of Ni(II)-induced common transcription-factor-governed
      pathways by discussing transcriptome alteration, its governing transcription
      factors and the underlying mechanism. Finally, we propose a putative target
      network of Ni(II) as a human carcinogen. 

PMID- 25069804
TI  - Bortezomib-induced peripheral neurotoxicity: an update.
AB  - This review paper provides a critical exploration of updates concerning the
      spectrum of characteristics and treatment options of bortezomib-induced
      peripheral neuropathy (BIPN). Emphasis is given on pathogenesis issues. Although
      the mechanism underlying BIPN still remains elusive, it is increasingly
      acknowledged that the inhibition of proteasome activity in dorsal root ganglia
      and peripheral nerves, the mitochondrial-mediated disruption of Ca++
      intracellular homeostasis and the disregulation in nuclear factor kappaB and
      brain-derived neurotrophic factor play a significant pathogenic role. Assessment
      of BIPN is based on comprehensive grading scales, using a combination of
      "subjective" and "objective" parameters, which turn out to be ambiguously
      interpreted, thus leading to both under- and misreporting of its true incidence
      and severity. BIPN is clinically defined as a typical example of a dose
      dependent, distally attenuated painful, sensory neuronopathy. Patients pre
      treated with neurotoxic regimens and those with pre-existing neuropathy are more
      likely to develop severe neurotoxicity. To date, there is no effective
      pharmacological treatment to prevent BIPN, and therefore, interventions remain
      merely symptomatic to focus on the alleviation of neuropathic pain. Hence, strict
      adherence to the dose reduction and schedule change algorithm is recommended in
      order to prevent treatment-emergent BIPN and allow the continuation of treatment.
      Further studies in animal models and humans, including experimental, clinical,
      neurophysiological and pharmacogenetic approaches, are needed to allow the
      identification of the true spectrum of BIPN pathogenesis and characteristics. It
      is expected that such comprehensive approaches would be the starting point for
      the development of early preventive and therapeutic interventions against BIPN.

PMID- 25069805
TI  - A companionship between strangers - learning from fellow people with cancer in
      oncology wards.
AB  - AIM: An identification and discussion of learning from experience among
      hospitalized people with cancer. BACKGROUND: A good deal of literature focuses on
      the fact that the needs of patients for information about their disease and
      treatment should be met by healthcare professionals. Less attention is given to
      the kind of information that can be provided by personal experience. Patient
      patient interaction as a learning situation has not been identified in current
      research. DESIGN: The study methodology was qualitative and influenced by
      ethnography. METHOD: A qualitative approach with participant observation and
      qualitative interviews was used. From a total of 85 observed people with cancer,
      ten men and ten women were interviewed in 2010-2011. Data were analysed using
      qualitative data analysis inspired by Ian Dey and structured using NVivo9.
      FINDINGS: The hospitalized patients learnt about life with cancer from sharing
      information and personal experiences with fellow patients. Information from
      fellow patients was complementary to information given by healthcare
      professionals. Sharing personal experiences led patients to oscillate between
      four general response stages: the response of fighting, the response of keeping
      hope, the response of non-acceptance and the response of capitulation.
      CONCLUSION: Learning from exchanges of experiences with fellow patients provided
      a better understanding about the disease and was valued because it was first-hand
      knowledge. Patients' personal experience of disease is an underused resource in
      nursing.

PMID- 25069807
TI  - Increased blood flow in the anterior humeral circumflex artery correlates with
      night pain in patients with rotator cuff tear.
AB  - BACKGROUND: Night pain is a particularly vexing symptom in patients with rotator
      cuff tear. It disturbs sleep and decreases quality of life, and there is no
      consensus regarding its etiology. Based on arthroscopic surgical observations of
      synovitis around the rotator interval or capsule surface in rotator cuff tear, we
      hypothesized that blood flow from the artery feeding the capsule increases blood
      supply to the synovium. This study aimed to investigate the relationship between
      blood flow and night pain using pulse Doppler ultrasonography. METHODS: A series
      of 47 consecutive patients with rotator cuff tear was evaluated. The peak
      systolic velocity and resistance index of blood flow in the ascending branch of
      the anterior humeral circumflex artery were evaluated using pulse Doppler
      ultrasonography. We also investigated 20 normal shoulders in healthy volunteers.
      The peak systolic velocity and resistance index were compared between affected
      and unaffected sides in patients and between dominant and nondominant sides in
      controls. RESULTS: Anterior humeral circumflex artery peak systolic velocity and
      resistance index did not differ between sides in control subjects or in patients
      with rotator cuff tear without night pain. However, anterior humeral circumflex
      artery peak systolic velocity and resistance index did differ significantly
      between sides in patients with rotator cuff tear with night pain. CONCLUSIONS:
      This study revealed anterior humeral circumflex artery hemodynamics in patients
      with rotator cuff tear and normal subjects using Doppler ultrasonography. Night
      pain, particularly involving aching, appears to be related to the hemodynamics.
      These findings suggest that investigating the hemodynamics of patients with
      rotator cuff tear with night pain may lead to greater understanding of the
      etiology of this symptom.

PMID- 25069806
TI  - Vitamin D status in non-supplemented postmenopausal Taiwanese women with
      osteoporosis and fragility fracture.
AB  - BACKGROUND: Vitamin D is essential for calcium metabolism, Vitamin D deficiency
      can precipitate osteoporosis, cause muscle weakness and increase the risk of
      fracture. The aim of this study was to assess the prevalence of vitamin D
      inadequacy among non-supplemented postmenopausal women with osteoporosis and
      fragility fractures of the hip or vertebrae in Taiwan. METHODS: This multi
      center, cross-sectional, observational study analyzed the vitamin D inadequacy
      [defined as 25(OH) D level less than 30 ng/mL] in Taiwanese postmenopausal
      osteoporotic patients who suffered from a low trauma, non-pathological fragility
      hip or vertebral fracture that received post-fracture medical care when admitted
      to hospital or at an outpatient clinic. RESULTS: A total of 199 patients were
      enrolled at 8 medical centers in Taiwan; 194 patients met the study criteria with
      113 (58.2%) and 81 (41.8%) patients diagnosed with hip and vertebral fracture,
      respectively. The mean serum 25(OH) D level was 21.1 +/- 9.3 ng/mL, resulting in
      a prevalence of vitamin D inadequacy of 86.6% of the patients. CONCLUSIONS: High
      prevalence of vitamin D inadequacy across all age groups was found among non
      supplemented women with osteoporosis and fragility hip or vertebral fracture in
      Taiwan.

PMID- 25069808
TI  - An outcome measure of functionality and quality of life in Iranian women with
      osteoporotic vertebral fractures: a validation study of the QUALEFFO-41.
AB  - BACKGROUND: Osteoporosis is a very common disease and often results in vertebral
      fractures. The Quality of Life Questionnaire of the European Foundation for
      Osteoporosis (QUALEFFO-41) is a tool to measure health-related quality of life in
      these patients. This study aimed to cross-culturally translate and validate the
      QUALEFFO-41 in Iran. METHODS: This was a prospective clinical validation study. A
      forward-backward procedure was used to translate the questionnaire from English
      into Persian. The translation and cross-cultural adaptation were made in
      accordance with published guidelines. Patients were divided into two study groups
      according to the World Health Organization criteria: those with at least one
      vertebral fracture who had undergone surgery and those with osteoporosis and no
      fractures as a control group. All of the participants were assessed by both the
      QUALEFFO-41 and SF-36. The surgery group was asked to respond to the QUALEFFO-41
      at two points in time: the pre- and postoperative assessments (6-month follow
      up). To test reliability, the internal consistency was evaluated using Cronbach's
      alpha coefficient. Validity was evaluated by assessing convergent validity
      between the QUALEFFO-41 and SF-36 and item-scale correlations and discriminatory
      ability. Internal responsiveness of the QUALEFFO-41 to the clinical intervention
      (surgery) also was evaluated comparing patients' pre- and postoperative scores.
      RESULTS: A total of 149 patients completed the questionnaire: 48 surgical
      patients and 101 as a control group. At the pre- and postoperative assessments,
      the QUALEFFO-41 showed adequate internal consistency in all domains (Cronbach's
      alpha of 0.71 to 0.81). Additionally, the correlation of each item with its
      hypothesized domain on the QUALEFFO-41 indicated acceptable results, suggesting
      that the items had a substantial relationship with their own domains. Further
      analysis also indicated that the questionnaire was responsive to change (P <
      0.0001). Significant correlations existed between scores of similar subscales of
      the QUALEFFO-41 and SF-36 (P < 0.001). CONCLUSIONS: The findings show that the
      Iranian version of the QUALEFFO-41 is a reliable and valid measure of
      functionality and quality-of-life evaluation among patients with osteoporotic
      vertebral fractures.

PMID- 25069809
TI  - Culture of the green microalga Botryococcus braunii Showa with LED irradiation
      eliminating violet light enhances hydrocarbon production and recovery.
AB  - The green microalga Botryococcus braunii (B. braunii), race B, was cultured under
      light-emitting diode (LED) irradiation with and without violet light. This study
      examined the effect of violet light on hydrocarbon recovery and production in B.
      braunii. C34 botryococcene hydrocarbons were efficiently extracted by thermal
      pretreatments at lower temperatures when the alga was cultured without violet
      light. The hydrocarbon content was also higher (approximately 3%) in samples
      cultured without violet light. To elucidate the mechanism of effective
      hydrocarbon recovery and production, we examined structural components of the
      extracellular matrix (ECM). The amounts of extracellular carotenoids and water
      soluble polymers extracted by thermal pretreatment from the ECM were decreased
      when the alga was cultured without violet light. These results indicate that LED
      irradiation without violet light is more effective for hydrocarbon recovery and
      production in B. braunii. Furthermore, structural ECM components are closely
      involved in hydrocarbon recovery and production in B. braunii. 

PMID- 25069810
TI  - IQuant: an automated pipeline for quantitative proteomics based upon isobaric
      tags.
AB  - Quantitative proteomics technology based on isobaric tags is playing an important
      role in proteomic investigation. In this paper, we present an automated software,
      named IQuant, which integrates a postprocessing tool of protein identification
      and advanced statistical algorithms to process the MS/MS signals generated from
      the peptides labeled by isobaric tags and aims at proteomics quantification. The
      software of IQuant, which is freely downloaded at
      http://sourceforge.net/projects/iquant/, can run from a graphical user interface
      and a command-line interface, and can work on both Windows and Linux systems. 

PMID- 25069811
TI  - Construct-related validity of the TOCS measures: comparison of intelligibility
      and speaking rate scores in children with and without speech disorders.
AB  - This study evaluated construct-related validity of the Test of Children's Speech
      (TOCS). Intelligibility scores obtained using open-set word identification tasks
      (orthographic transcription) for the TOCS word and sentence tests and rate scores
      for the TOCS sentence test (words per minute or WPM and intelligible words per
      minute or IWPM) were compared for a group of 15 adults (18-30 years of age) with
      normal speech production and three groups of children: 48 3-6 year-olds with
      typical speech development and neurological histories (TDS), 48 3-6 year-olds
      with a speech sound disorder of unknown origin and no identified neurological
      impairment (SSD-UNK), and 22 3-10 year-olds with dysarthria and cerebral palsy
      (DYS). As expected, mean intelligibility scores and rates increased with age in
      the TDS group. However, word test intelligibility, WPM and IWPM scores for the 6
      year-olds in the TDS group were significantly lower than those for the adults.
      The DYS group had significantly lower word and sentence test intelligibility and
      WPM and IWPM scores than the TDS and SSD-UNK groups. Compared to the TDS group,
      the SSD-UNK group also had significantly lower intelligibility scores for the
      word and sentence tests, and significantly lower IWPM, but not WPM scores on the
      sentence test. The results support the construct-related validity of TOCS as a
      tool for obtaining intelligibility and rate scores that are sensitive to group
      differences in 3-6 year-old children, with and without speech sound disorders,
      and to 3+ year-old children with speech disorders, with and without dysarthria.
      LEARNING OUTCOMES: Readers will describe the word and sentence intelligibility
      and speaking rate performance of children with typically developing speech at age
      levels of 3, 4, 5 and 6 years, as measured by the Test of Children's Speech, and
      how these compare with adult speakers and two groups of children with speech
      disorders. They will also recognize what measures on this test differentiate
      children with speech sound disorders of unknown origin from children with
      cerebral palsy and dysarthria.

PMID- 25069812
TI  - Carotid artery stenosis is exacerbated in spontaneously obese model rats with
      diabetes.
AB  - AIM: Population studies have shown obesity and diabetes to be risk factors for
      atherosclerosis. We assessed changes in the common carotid arteries in rat models
      of obesity and diabetes without hypertension. METHODS: Twenty 30-week-old male
      spontaneously diabetic and obese model Otsuka Long-Evans Tokushima Fatty (OLETF)
      and 20 control Long-Evans Tokushima Otsuka (LETO) rats were used in the
      experiments. The animals were considered diabetic if the plasma glucose level
      peaked at >300 mg/dL and remained at >200 mg/dL for 120 minutes. Blood gas
      physiological parameters were continuously monitored under anesthesia, and the
      flow of the carotid artery was assessed with ultrasonography. All animals were
      sacrificed with an overdose of anesthesia at the end of the experiment. Sections
      of the middle portion of the internal carotid artery were cut and stained with
      hematoxylin and eosin to assess the overall morphology. RESULTS: All OLETF rats
      were diabetic, and all LETO rats were non-diabetic. The physiological parameters
      did not differ significantly between the control and model rats, whereas the
      carotid artery wall thickness (19.3 +/- 3.2 vs. 6.1 +/- 4.5 MUm) was
      significantly different between the two groups. The blood flow velocity in the
      common carotid artery determined using ultrasonography and color Doppler
      sonography was significantly increased during systole in the model rats compared
      with that observed in the control rats (203 +/- 20.3 vs. 55.3 +/- 21.4 cm/sec).
      CONCLUSIONS: The OLETF rats were obese, and diabetes worsened the degree of
      carotid artery stenosis. These results indicate the possibility of new therapies
      for carotid artery stenosis in obese and diabetic patients.

PMID- 25069815
TI  - Assessment of coronary atherosclerosis using optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a catheter-based imaging system that uses
      near-infrared light to produce cross-sectional images of the coronary arteries.
      With its extraordinarily high resolution (10-20 MUm), OCT allows clinicians to
      observe various morphological features of coronary atherosclerosis in vivo. For
      example, intimal thickening presents as homogeneous, signal-rich regions on OCT,
      while fibroatheroma with a lipid-rich necrotic core is characterized by the
      presence of signal-poor regions with a diffuse border. Furthermore, plaque
      rupture is detected in 50~70% of culprit lesions of acute coronary syndrome
      (ACS), and plaque erosion develops over areas of intimal thickening and/or thick
      cap fibroatheroma. Meanwhile, calcified nodules are common in older patients with
      hypertension and chronic renal disease. Platelet-rich thrombi are visualized as
      low backscattering structures and often detected in patients with unstable
      angina, whereas red blood cell-rich thrombi exhibit a high backscattering
      structure with signal-free shadowing and are frequently noted in patients with
      acute myocardial infarction. Moreover, OCT-derived thin cap fibroatheroma has
      been shown to be a predictor of subsequent plaque progression and acute coronary
      events, while vasa vasorum and the macrophage density are associated with a thin
      fibrous cap and large necrotic core as well as increased serum levels of
      inflammatory biomarkers. One current challenge of OCT examinations is to detect
      morphologic characteristics capable of discriminating vulnerable from stable
      plaques. The ability to detect vulnerable plaques in vivo would allow physicians
      to identify patients at high risk for adverse coronary events, thus significantly
      helping to prevent ACS.

PMID- 25069813
TI  - Lipid-lowering treatment practice patterns in korea: comparison with the data
      obtained from the CEPHEUS Pan-Asian study.
AB  - AIM: The Pan-Asian CEPHEUS study assessed low-density lipoprotein cholesterol
      (LDL-C) goal attainment among patients under lipid-lowering therapy. We compared
      Korean and other Asian data in order to investigate international variations in
      clinical practice in the field of cardiology. METHODS: Hypercholesterolemic
      patients >=18 years of age who had been on lipid-lowering treatment for >=3
      months were recruited from eight Asian countries. The lipid concentrations were
      measured, and demographic and other relevant data were collected. In addition,
      the cardiovascular risk was determined using criteria established in the updated
      2004 NCEP guidelines. RESULTS: In Korea, 92 cardiologists enrolled 1,584
      patients. The data of these patients were compared with those for 2,060 patients
      enrolled by 135 cardiologists from other Asian countries in the CEPHEUS study.
      The proportion of high-risk patients, frequency of use of more potent LDL-C
      lowering regimens and rate of LDL-C goal attainment were significantly greater in
      the Korean subjects than those observed in the other Asian populations. In
      addition, the Korean patients were more likely to achieve the LDL-C target (odds
      ratio=1.37, 95% confidence interval 1.11-1.70) after adjusting for the LDL-C
      target level, use of potent LDL-C-lowering regimens, the baseline LDL-C level,
      age and systolic blood pressure. CONCLUSIONS: There was a significant difference
      in the goal attainment rate between Korea and the other Asian countries. Korean
      cardiologists appear to be relatively more aggressive with lipid-lowering
      treatment than other Asian cardiologists.

PMID- 25069817
TI  - A multi-step method with signal quality assessment and fine-tuning procedure to
      locate maternal and fetal QRS complexes from abdominal ECG recordings.
AB  - Non-invasive monitoring of fetal electrocardiogram (fECG) plays an important role
      in detecting and diagnosing fetal diseases. This study aimed to develop a multi
      step method for locating both maternal and fetal QRS complexes from abdominal ECG
      (aECG) recordings. The proposed method included four major steps: abdominal ECG
      pre-processing, maternal QRS complex locating, maternal ECG cancellation and
      fetal QRS complex locating. Signal quality assessment (SQA) and fine-tuning for
      maternal ECG (FTM) were implemented in the first and third steps, respectively.
      The method was then evaluated using 75 non-invasive 4-channel aECG recordings
      provided by the PhysioNet/Computing in Cardiology Challenge 2013. The F1 measure,
      which is a new index introduced by Behar et al (2013 Proc. Comput. Cardiol. 40
      297-300), was used to assess the locating accuracy. The other two indices, mean
      squared error of heart rate (MSE_HR) between the fetal HR signals estimated from
      the reference and our method (MSE_HR in bpm(2)) and root mean squared difference
      between the corresponding fetal RR intervals (MSE_RR in ms) were also used to
      assess the locating accuracy. Overall, for the maternal QRS complex, the F1
      measure was 98.4% from the method without the implementation of SQA, and it was
      improved to 99.8% with SQA. For the fetal QRS complex, the F1 measure, MSE_HR and
      MSE_RR were 84.9%, 185.6 bpm(2) and 19.4 ms for the method without both SQA and
      FTM procedures. They were improved to 93.9%, 47.5 bpm(2) and 7.6 ms with both SQA
      and FTM procedures. These improvements were observed from each individual
      subject. It can be concluded that implementing both SQA and FTM procedures could
      achieve better performance for locating both maternal and fetal QRS complexes. 

PMID- 25069816
TI  - Usefulness of the neutrophil-to-lymphocyte ratio in predicting the severity of
      coronary artery disease: a Gensini score assessment.
AB  - AIM: The usefulness of the white blood cell (WBC) count and neutrophil-to
      lymphocyte ratio (NLR) in predicting the severity of stable coronary artery
      disease (CAD) has not been sufficiently evaluated, particularly based on strict
      coronary assessments. The aim of the present study was to investigate the WBC
      count and NLR in predicting the severity of angiographically proven CAD. METHODS:
      A total of 2,976 CAD patients and 571 non-CAD patients were consecutively
      enrolled, and the CAD patients were classified into the three groups according to
      the tertile of the Gensini score (GS, low GS<18, n=989; intermediate GS 18-41,
      n=995 and high GS>41, n=992). The efficacy of the WBC count and NLR in predicting
      the risk and severity of CAD as well as the correlations between these markers
      and the GS were analyzed. A receiver operating characteristic (ROC) curve
      analysis was also performed. RESULTS: The NLR was found to be an independent
      predictor of both the presence of CAD (OR=1.18, 95%CI: 1.09-1.27, p=0.009) and a
      high GS (OR=1.10, 95%CI: 1.01-1.16, p=0.032). In addition, there were mild
      positive correlations between the GS and the NLR, WBC and proportions of
      neutrophils and monocytes. In the ROC curves analysis, the NLR was found to have
      the largest area under the curve (AUC=0.63, 95%CI: 0.59-0.67, p=0.000), with an
      optimal cut-off value of 2.04 (sensitivity: 62.1%, specificity: 54.8%) for
      predicting a high GS. CONCLUSIONS: The NLR is a valuable independent predictor of
      the severity of CAD assessed according to the GS. In particular, an NLR of >2.04
      indicates a higher risk of CAD and greater severity of CAD lesions.

PMID- 25069814
TI  - Short-term venous stasis induces fibrinolytic activation but not thrombin
      formation.
AB  - AIM: Venous stasis is a well-known risk factor for the development of venous
      thromboembolism. It is likely that stasis increases the risk of thrombosis by
      inducing hypercoagulability via the hypoxic procoagulant activation of
      endothelial and mononuclear cells and the accumulation of activated clotting
      factors. However, increased rates of thrombin formation have not been
      demonstrated in response to venous stasis in vivo. METHODS: In this study, we
      used the venous occlusion (VO) test to determine, if stasis triggers thrombin
      formation in healthy individuals (n=25) and patients with additional thrombotic
      risk factors, such as inherited thrombophilia (n=19) and symptomatic
      atherosclerosis (n=15). Thrombin formation was monitored by measuring plasma
      levels of free thrombin using a highly sensitive oligonucleotide enzyme capture
      assay (OECA) in addition to the plasma levels of prothrombin fragment 1+2 (F1+2)
      and thrombin-antithrombin-complexes (TAT). The plasma levels of activated protein
      C (APC) were additionally measured using an APC-OECA. RESULTS: VO induced a
      significant (p<0.05) increase in the levels of tissue-type plasminogen activator
      and plasmin-alpha2-antiplasmin-complexes. In all three cohorts, the majority of
      samples obtained during VO showed no quantifiable thrombin or APC levels.
      Consistent with these findings F1+2 and TAT did not change. CONCLUSIONS: We
      conclude that short-term venous stasis induces a profibrinolytic response due to
      the activation of endothelial cells, but not a prothrombotic response, even in
      the presence of additional thrombophilic risk factors. Furthermore, our results
      support the hypothesis that the stasis-induced profibrinolytic activation of
      endothelial cells occurs independently from thrombin formation.

PMID- 25069818
TI  - Repeated loss of frontal sinuses in arctoid carnivorans.
AB  - Many mammal skulls contain air spaces inside the bones surrounding the nasal
      chamber including the frontal, maxilla, ethmoid, and sphenoid, all of which are
      called paranasal sinuses. Within the Carnivora, frontal sinuses are usually
      present, but vary widely in size and shape. The causes of this variation are
      unclear, although there are some functional associations, such as a correlation
      between expanded frontal sinuses and a durophagous diet in some species (e.g.,
      hyenas) or between absent sinuses and semiaquatic lifestyle (e.g., pinnipeds). To
      better understand disparity in frontal sinus morphology within Carnivora, we
      quantified frontal sinus size in relationship to skull size and shape in 23
      species within Arctoidea, a clade that is ecologically diverse including three
      independent invasions of aquatic habitats, by bears, otters, and pinnipeds,
      respectively. Our sampled species range in behavior from terrestrial (rarely or
      never forage in water), to semiterrestrial (forage in water and on land), to
      semiaquatic (forage only in water). Results show that sinuses are either lost or
      reduced in both semiterrestrial and semiaquatic species, and that sinus size is
      related to skull size and shape. Among terrestrial species, frontal sinus size
      was positively allometric overall, but several terrestrial species completely
      lacked sinuses, including two fossorial badgers, the kinkajou (a nocturnal,
      arboreal frugivore), and several species with small body size, indicating that
      factors other than aquatic habits, such as space limitations due to constraints
      on skull size and shape, can limit sinus size and presence.

PMID- 25069819
TI  - Pseudochromhidrosis: the role of dermoscopy in diagnosis.

PMID- 25069820
TI  - Validation of an LC-MS/MS method for the determination of zopiclone, N
      desmethylzopiclone and 2-amino-5-chloropyridine in whole blood and its
      application to estimate the original zopiclone concentration in stored specimens.
AB  - 2-Amino-5-chloropyridine (ACP) is a degradation product of zopiclone (ZOP) and
      its two main metabolites N-desmethylzopiclone (NDZOP) and zopiclone N-oxide
      (ZOPNO). ACP may be formed when specimens are stored. ZOP instability in blood
      makes interpretation of concentrations difficult especially in cases of prolonged
      sample storage. This study investigated how ACP could be used to estimate the
      original concentration of ZOP in authentic samples. For that purpose, an
      analytical liquid chromatography tandem mass spectrometry (LC-MS/MS) method for
      the quantitation of ACP, ZOP, and NDZOP in blood was developed and validated. Due
      to poor extraction recovery, ZOPNO was not included in the analytical method. The
      method was then applied to investigate ACP formation, ZOP and NDZOP degradation
      in stored ZOP post-dosed authentic whole blood and two mathematical models were
      used to calculate the original concentration of ZOP. During storage, ACP was
      formed in amounts equimolar to the ZOP and NDZOP degradation. Results from
      samples in which ACP had been formed were used to test two models to estimate the
      original ZOP concentration. The correlation tests of the models showed strong
      correlations to the original ZOP concentration (r = 0.960 and r = 0.955) with p <
      0.01 and explained more than 90 % of the ZOP concentration. This study showed
      that the equimolar degradation of ZOP and NDZOP to ACP could be used to estimate
      the original concentration of ZOP. 

PMID- 25069821
TI  - Paraoxonase 1 deficiency and hyperhomocysteinemia alter the expression of mouse
      kidney proteins involved in renal disease.
AB  - SCOPE: Hyperhomocysteinemia (HHcy) is associated with kidney disease and leads to
      atherosclerosis and thrombosis. Paraoxonase 1 (Pon1), a hydrolase that
      participates in homocysteine (Hcy) metabolism and is carried in the circulation
      on high-density lipoprotein, has also been linked to kidney disease and
      atherothrombosis. Pon1-knockout mice are susceptible to atherosclerosis and
      exhibit a kidney-associated phenotype, polyuria or urine dilution. We hypothesize
      that HHcy and Pon1 deficiency are toxic to kidney function because they impair
      metabolic pathways important for normal kidney homeostasis. METHODS AND RESULTS:
      We examined changes in the mouse kidney proteome induced by Pon1 gene deletion
      and dietary HHcy, using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass
      spectrometry. We found that the expression of ten mouse kidney proteins was
      altered by the Pon1(-/-) genotype or HHcy. Proteins involved in metabolism of
      lipid (ApoA-I), protein (Hspd1), carbohydrate (Pdhb, Fbp1-isoform2, Eno1), and
      energy (Ndufs8, Ldhd) were down-regulated. Proteins involved in lipid transport
      (Pebp1), oxidative stress response (Prdx2), and cellular detoxification (Glo1)
      were up-regulated. The kidney proteins altered by HHcy or Pon1 are also altered
      in renal disease. CONCLUSION: Our findings suggest that excess Hcy is toxic
      because it deregulates the expression of proteins involved in diverse cellular
      processes-from lipid, protein, carbohydrate, and energy metabolisms to
      detoxification and antioxidant defenses-that are essential for normal kidney
      homeostasis. Dysregulation of these processes can account for the involvement of
      HHcy and reduced Pon1 in kidney disease. Our findings also show that Pon1 plays
      an important role in maintaining normal kidney homeostasis.

PMID- 25069822
TI  - A zebrafish model of hyperammonemia.
AB  - Hyperammonemia is the principal consequence of urea cycle defects and liver
      failure, and the exposure of the brain to elevated ammonia concentrations leads
      to a wide range of neuro-cognitive deficits, intellectual disabilities, coma and
      death. Current treatments focus almost exclusively on either reducing ammonia
      levels through the activation of alternative pathways for ammonia disposal or on
      liver transplantation. Ammonia is toxic to most fish and its pathophysiology
      appears to be similar to that in mammals. Since hyperammonemia can be induced in
      fish simply by immersing them in water with elevated concentration of ammonia, we
      sought to develop a zebrafish (Danio rerio) model of hyperammonemia. When exposed
      to 3mM ammonium acetate (NH4Ac), 50% of 4-day old (dpf) fish died within 3hours
      and 4mM NH4Ac was 100% lethal. We used 4dpf zebrafish exposed to 4mM NH4Ac to
      test whether the glutamine synthetase inhibitor methionine sulfoximine (MSO)
      and/or NMDA receptor antagonists MK-801, memantine and ketamine, which are known
      to protect the mammalian brain from hyperammonemia, prolong survival of
      hyperammonemic fish. MSO, MK-801, memantine and ketamine all prolonged the lives
      of the ammonia-treated fish. Treatment with the combination of MSO and an NMDA
      receptor antagonist was more effective than either drug alone. These results
      suggest that zebrafish can be used to screen for ammonia-neuroprotective agents.
      If successful, drugs that are discovered in this screen could complement current
      treatment approaches to improve the outcome of patients with hyperammonemia. 

PMID- 25069824
TI  - Coexistence effect of UVA absorbers to increase their solubility and stability of
      supersaturation.
AB  - OBJECTIVE: Sunscreens containing UVA absorbers in high concentrations are
      expected to be developed, since recent studies have suggested the possibility of
      involvement of UVA ray in skin cancer and early skin aging. Solubility and
      stability of supersaturation of UVA absorbers in UVB absorber were determined in
      the absence and the presence of cosmetic oil. Coexistence effect of UVA absorbers
      was analyzed to dissolve them in high concentrations. METHODS: Two UVA absorbers,
      diethylamino hydroxybenzoyl hexyl benzoate (DHHB) and butyl
      methoxydibenzoylmethane (BMDM), a UVB absorber, 2-ethylhexyl methoxycinnamate
      (EHMC), and a cosmetic oil, 2-ethylhexyl ester of oligomer of hydroxystearic acid
      (EH-O-HSA), were used. Their solutions were prepared at 80 degrees C and cooled
      to 5 degrees C. The solid DHHB and/or BMDM were added to it, and the time
      evolution of concentrations of the UVA absorbers in the solution phase was
      monitored. RESULTS: At the saturation in the absence of EH-O-HSA at 5 degrees C,
      weight ratio of DHHB and BMDM to EHMC was 0.39/1.00 and 0.22/1.00, respectively.
      Addition of EH-O-HSA slightly changed the solubility of DHHB and BMDM. When the
      weight ratio of EH-O-HSA to EHMC was 0.20/1.00, weight ratio of DHHB and BMDM to
      EHMC was 0.35/1.00 and 0.25/1.00, respectively at the saturation at 5 degrees C.
      In the presence of EH-O-HSA, a strong coexistence effect of DHHB and BMDM was
      found on their solubility. A thermodynamically stable saturated solution at 5
      degrees C having the composition that DHHB: BMDM: EHMC: EH-O-HSA = 0.47: 0.46:
      1.00: 0.20 was obtained by the simultaneous addition of solid DHHB and BMDM into
      the initial solution. CONCLUSION: The solution type composite having the highest
      concentrations of DHHB and BMDM prepared in this study exhibited critical
      wavelength at 368 nm that was just below the border for sunscreens being
      qualified as 'Broad Spectrum' protection under the new rule launched by US FDA.

PMID- 25069823
TI  - Eukaryotic elongation factor 2 kinase controls proliferation and migration of
      vascular smooth muscle cells.
AB  - AIM: Eukaryotic elongation factor 2 kinase (eEF2K), also known as calmodulin
      (CaM)-dependent protein kinase (CaMK) III, is a unique member of CaMK family
      protein. We have recently found that expression of eEF2K protein increased in
      mesenteric artery from spontaneously hypertensive rats. As pathogenesis of
      hypertension is in part regulated by vascular structural remodelling via
      proliferation and migration of vascular smooth muscle cells (SMCs), we tested the
      hypothesis that eEF2K controls SMCs proliferation and migration. METHODSAND
      RESULTS: In rat mesenteric arterial SMCs, an eEF2K inhibitor, A-484954 (10 MUm),
      significantly inhibited platelet-derived growth factor (PDGF)-BB (10 ng mL(-1) )
      induced SMCs proliferation as determined by a cell counting and bromodeoxyuridine
      incorporation assay. PDGF-BB (10 ng mL(-1) )-induced SMCs migration was
      significantly inhibited by A-484954 (10 MUm) as determined by a Boyden chamber
      assay. A-484954 (10 MUm) significantly inhibited PDGF-BB (10 ng mL(-1) )-induced
      phosphorylation of eEF2K, extracellular signal-regulated kinase (ERK), Akt, p38
      and heat-shock protein (HSP) 27 as determined by Western blotting. It was
      confirmed that a CaM inhibitor, W-7 (50 MUm), inhibited PDGF-BB (10 ng mL(-1) )
      induced phosphorylation of eEF2K. In an ex vivo mesenteric arterial ring assay,
      10% foetal bovine serum-induced SMCs outgrowth was significantly inhibited by A
      484954 (10 MUm). CONCLUSION: We for the first time revealed that eEF2K mediates
      PDGF-BB-induced SMCs proliferation and migration through activating ERK, Akt, p38
      and HSP27 signals in a CaM-dependent manner. Our results suggest eEF2K as a novel
      pharmaceutical target for the prevention of hypertensive cardiovascular diseases.

PMID- 25069825
TI  - Cyclodextrin polyrotaxanes as a highly modular platform for the development of
      imaging agents.
AB  - Selectively functionalized cyclodextrins with a bodipy fluorescent tag or Gd(3+)
      complex were synthetized and threaded onto a polyammonium chain to form
      polyrotaxanes. This modular supramolecular assembly makes an ideal platform for
      bimodal (fluorescent and MRI) imaging applications. 

PMID- 25069826
TI  - The significance of hypersensitivity to autologous sweat and serum in cholinergic
      urticaria: cholinergic urticaria may have different subtypes.
AB  - BACKGROUND: The pathogenesis of cholinergic urticaria (ChU) has been unclear
      except for the involvement of acetylcholine. Attempts to classify ChU according
      to etiology have rarely been performed. OBJECTIVE: To evaluate the significance
      of responsiveness to autologous sweat and serum in ChU in relation to their
      clinical characteristics. METHODS: This study involved 18 patients diagnosed with
      ChU between January 2010 and April 2011 in the Catholic Medical Center-St. Paul's
      Hospital. History taking included symptom duration, association with atopy,
      decreased sweat secretions, seasonal variation, and response to treatment.
      Intradermal autologous serum skin test (ASST) and autologous sweat skin test
      (ASwST) and basophil histamine release test with sweat were done. RESULTS: Sweat
      hypersensitivity was proven by a positive ASwST and basophil histamine release
      test in only 37.5% of patients with ChU, and in none of the healthy controls. The
      weal size of ASwST correlated with percentage basophil histamine release. A
      positive response to autologous serum was displayed by 38.9% of patients, whereas
      10% of healthy controls showed a positive ASST response. Intriguingly, patients
      with a positive ASwST had a negative ASST, and vice versa. Despite this, there
      was no difference in the clinical characteristics between positive ASST and
      positive ASwST groups. CONCLUSIONS: The frequency of hypersensitivity to
      autologous sweat and serum was significantly higher in patients with ChU,
      compared with healthy controls. This suggests that autoimmunity to an unknown
      serum factor as well as sweat hypersensitivity may be involved in the
      pathogenesis of ChU.

PMID- 25069827
TI  - Application of Kinect gaming sensor in forensic science.
AB  - Kinect sensor appears as a low-cost option for 3D modeling. This manuscript
      describes a methodology to test the applicability of Kinect to crime scenes. The
      methodology includes the comparison versus well-established scanners (Faro and
      Trimble). The parameters used for the comparison are the quality in the fitting
      of primitives, a qualitative evaluation of facial data, the data quality for
      different ranges, and the accuracy in the measurement of different lengths. The
      results show that the Kinect noise level increases with range, from 5 mm at 1.5 m
      range to 15 mm at 3 m range. It is considered that for detail measurements the
      sensor must be placed close to the target. A general measurement of a sample
      crime scene was analyzed. Errors in length measurements are between 2% and 10%
      for 3 m range. The measurement range must be limited to c. 3 m.

PMID- 25069828
TI  - [Lower limb salvage with a free fillet fibula flap harvested from the
      contralateral amputated leg].
AB  - We report a unusual case of "fillet flap" to reconstruct the lower limb with the
      amputated contralateral leg. This kind of procedure was first described by
      Foucher et al. in 1980 for traumatic hand surgery as the "bank finger". A 34-year
      old man suffered a microlight accident with bilateral open legs fractures. A
      large skin defect of the left leg exposed the ankle, the calcaneus and a non
      vascularized part of the tibial nerve (10 cm). The patient came to the OR for
      surgical debridement and had massive bone resection of the left calcaneus. The
      right leg showed limited skin defect at the lower part, exposing the medial side
      of the ankle and a tibial bone defect, measuring 10 cm. Salvage the left leg was
      impossible due to complex nerve, bones and skin associated injuries, so this leg
      was sacrificed and used as a donor limb, to harvest a free fibula flap for
      contralateral tibial reconstruction. At 18 months of follow-up, the patient was
      very satisfied, the clinical result was very good on both lower limbs and X-rays
      showed excellent integration of the free fibula flap. The patient had normal
      dailies occupations, can run and have bicycle sport practice with a functional
      left leg fit prosthesis. This case showed an original application of the "fillet
      flap concept" to resolve complex and rare traumatic situations interesting the
      both lower limbs. In our opinion, this strategy must be a part of the plastic
      surgeon skills in uncommon situations.

PMID- 25069829
TI  - Total synthesis of oxazolomycins.
AB  - The oxazolomycin family of antibiotics, isolated from several Streptomyces
      strains, are intriguing molecules for synthesis due to their characteristic
      oxazole polyene lactam-lactone structures and significant antiviral,
      antibacterial, and antitumor biological activities. In the last ten years, we
      have been addressing synthetic problems to accomplish the total syntheses of
      neooxazolomycin and oxazolomycin A as well as the related antibiotics,
      inthomycins A, B, and C, which have truncated structures corresponding to the
      left-hand fragments. This account describes an overview of our synthetic efforts
      toward these natural products focusing on the strategies and methodologies we
      devised. 

PMID- 25069831
TI  - Things you can learn from books: exploring the therapeutic potential of eating
      disorder memoirs.
AB  - This paper explores the potential benefits that books, and specifically memoirs,
      might offer mental health students, positing that first-person testimonials might
      make the complex experiences of a mental health challenge, in this case, eating
      disorders, accessible to learners. The paper presents a pedagogical approach,
      based on transformative learning, to assist in encouraging the development of a
      recovery approach in students. Transformative learning is a pedagogy that is
      interested in problematic practices that keep afflicting an area, such as the
      imbalanced focus on learning illness, rather than well-being, and in pondering
      and revising the educational solutions. The paper proposes that forward movement
      in this area will be based on considering and developing such innovative
      curricula, and researching its impact. By virtue of their accessibility, memoirs
      could offer to a large audience the benefits of universality, empathy, hope, and
      guidance. Teachers and learners could be making use of these books in face-to
      face or online activities. This paper explores the groundwork that is needed
      before eating disorder memoirs can be confidently recommended as a therapeutic
      tool. 

PMID- 25069830
TI  - The effect of secondary inorganic aerosols, soot and the geographical origin of
      air mass on acute myocardial infarction hospitalisations in Gothenburg, Sweden
      during 1985-2010: a case-crossover study.
AB  - BACKGROUND: The relative importance of different sources of air pollution for
      cardiovascular disease is unclear. The aims were to compare the associations
      between acute myocardial infarction (AMI) hospitalisations in Gothenburg, Sweden
      and 1) the long-range transported (LRT) particle fraction, 2) the remaining
      particle fraction, 3) geographical air mass origin, and 4) influence of local
      dispersion during 1985-2010. METHODS: A case-crossover design was applied using
      lag0 (the exposure the same day as hospitalisation), lag1 (exposure one day prior
      hospitalisation) and 2-day cumulative average exposure (CA2) (mean of lag0 and
      lag1). The LRT fractions included PMion (sum of sulphate, nitrate and ammonium)
      and soot measured at a rural site. The difference between urban PM10 (particulate
      matter with an aerodynamic diameter smaller than 10 MUm) and rural PMion was a
      proxy for locally generated PM10 (PMrest). The daily geographical origin of air
      mass was estimated as well as days with limited or effective local dispersion.
      The entire year was considered, as well as warm and cold periods, and different
      time periods. RESULTS: In total 28 215 AMI hospitalisations occurred during 26
      years. PM10, PMion, PMrest and soot did not influence AMI for the entire year. In
      the cold period, the association was somewhat stronger for PMrest than for urban
      PM10; the strongest associations were observed during 1990-2000 between AMI and
      CA2 of PMrest (6.6% per inter-quartile range (IQR), 95% confidence interval 2.1
      to 11.4%) and PM10 (4.1%, 95% CI 0.2% - 8.2%). Regarding the geographical air
      mass origins there were few associations. Days with limited local dispersion
      showed an association with AMI in the cold period of 2001-2010 (6.7%, 95% CI 0.0%
      - 13.0%). CONCLUSIONS: In the cold period, locally generated PM and days with
      limited local dispersion affected AMI hospitalisations, indicating importance of
      local emissions from e.g. traffic.

PMID- 25069833
TI  - Familial amyloid polyneuropathy: elaboration of a therapeutic patient education
      programme, "EdAmyl".
AB  - BACKGROUND: Transthyretin-related amyloidosis (ATTR) is an autosomal dominant
      disease affecting the peripheral and autonomic nervous system, heart, eyes and
      kidneys. It is the most disabling hereditary polyneuropathy in adults. The French
      National Reference centre for this disease was accredited in 2005 with 10 lines
      of action. One of them is to inform and educate patients about their disease to
      improve their care and reduce morbidities. We thus decided to elaborate a
      therapeutic patient education (TPE) programme, starting with patients' needs
      assessment. METHODS: A qualitative research study was conducted with one-to-one
      semi-structured interviews of selected individuals. Recorded interviews were
      analysed to identify the skills that patients need to acquire. A TPE programme
      was elaborated on the basis of these findings. RESULTS: Seven patients, one
      asymptomatic carrier and two healthy spouses were interviewed. Analysis of the
      interviews showed that interviewees had a good knowledge of the disease and its
      symptoms but they had difficulties explaining the disease mechanism and did not
      have an adequate knowledge of the available treatment options, although they knew
      that liver transplant might halt progression of the disease. ATTR amyloidosis
      appeared to have a major negative impact on the patient's physical and mental
      well-being. Patients feared loss of autonomy and having to require assistance
      from their relatives and spouses. All interviewees were keen to participate in a
      TPE programme. Based on this needs assessment, we identified seven skills that
      patients need to acquire and several pedagogical goals to be achieved during the
      education programme. An interdisciplinary team then elaborated a complete TPE
      programme. CONCLUSION: Elaboration of a TPE programme for ATTR amyloidosis
      required to obtain useful information from the patients themselves, and their
      relatives, concerning their perception of their disease. This needs' assessment
      constituted the basis for designing the first TPE programme, to our knowledge,
      for ATTR amyloidosis. After translation, this programme could be applied in other
      EU countries and worldwide for this rare disease.

PMID- 25069834
TI  - Cannabis potency in the Venice area (Italy): update 2013.

PMID- 25069832
TI  - MicroRNA-18a inhibits hypoxia-inducible factor 1alpha activity and lung
      metastasis in basal breast cancers.
AB  - INTRODUCTION: In breast cancer, distinct expression profiles of microRNAs
      (miRNAs) have been associated with molecular subgroups and clinicopathological
      characteristics, implicating a diagnostic and prognostic role of miRNAs. However,
      the biological functions of deregulated miRNAs in tumor progression are not yet
      completely defined. In this study, we investigated the function of miR-18a in
      regulating breast cancer metastasis through the hypoxia-inducible factor 1alpha
      (HIF1A)-dependent hypoxic response. METHODS: An orthotopic metastatic breast
      cancer xenograft model (MDA-MB-231 cells) was used to identify miRNAs associated
      with spontaneous lung metastasis. The function of miR-18a in regulating HIF1A
      expression, as well as cellular responses to hypoxia and metastasis, were then
      studied in vitro and in vivo by assessing ectopic miR-18a expression or miR-18a
      inhibition. miRNA-mRNA interactions (AGO2 immunoprecipitation and 3' untranslated
      region Luciferase reporter assays), gene expression (quantitative PCR and
      microarray), cell migration and invasion, and cell growth were assessed under
      normoxic or hypoxic conditions, complemented by orthotopic xenograft of tumor
      cells to the mammary fat pad to investigate the effect of modulating miR-18a
      expression on primary tumor growth and lung metastasis. Last, clinically relevant
      correlations between miR-18a, HIF1A, hypoxia-responsive gene expression and
      distant metastasis-free survival (DMFS) were assessed using published expression
      array breast tumors data sets. RESULTS: miRNAs encoded by the MIR17HG gene were
      downregulated in lung metastases compared to primary tumors. Ectopic expression
      of miR-18a, a MIR17HG family member, in a metastatic variant of MDA-MB-231 cells
      reduced primary tumor growth and lung metastasis, whereas miR-18a inhibition in
      the parental cells promoted tumor growth and lung metastasis. We identified HIF1A
      as a direct target of miR-18a. Modulating miR-18a expression significantly
      affected hypoxic gene expression, cell invasiveness and sensitivity to anoikis
      and hypoxia in vitro in a HIF1A-dependent manner. Analysis of previously
      published data revealed that higher expression of HIF1A and a panel of hypoxic
      genes is associated with shorter DMFS interval in patients with basal-like breast
      tumors, and that, within this subtype, miR-18a expression is inversely correlated
      with hypoxic gene expression. Together, these data support a role of miR-18a in
      repressing distant metastasis through a HIF1A-dependent pathway. CONCLUSIONS: The
      results of this study reveal a novel role for miR-18a in targeting HIF1A and
      repressing metastasis of basal-like breast tumors.

PMID- 25069835
TI  - Nano-composites for water remediation: a review.
AB  - As global populations continue to increase, the pressure on water supplies will
      inevitably intensify. Consequently the international need for more efficient and
      cost effective water remediation technologies will also rise. The introduction of
      nano-technology into the industry may represent a significant advancement and
      zero-valent iron nano-particles (INPs) have been thoroughly studied for potential
      remediation applications. However, the application of water dispersed INP
      suspensions is limited and somewhat contentious on the grounds of safety, whilst
      INP reaction mechanisms, transport properties and ecotoxicity are areas still
      under investigation. Theoretically, the development of nano-composites containing
      INPs to overcome these issues provides the logical next step for developing nano
      materials that are better suited to wide application across the water industry.
      This review provides an overview of the range of static, bulk nano-composites
      containing INPs being developed, whilst highlighting the limitations of
      individual solutions, overall classes of technology, and lack of comparative
      testing for nano-composites. The review discusses what further developments are
      needed to optimize nano-composite water remediation systems to subsequently
      achieve commercial maturity. 

PMID- 25069836
TI  - The therapy of insulin resistance in other diseases besides type 2 diabetes.
AB  - Insulin resistance is a clinical condition shared by many diseases besides type 2
      diabetes (T2DM) such as obesity, polycystic ovary syndrome (PCOS) and non
      alcoholic fatty liver disease (NAFLD). Experimental evidence, produced over the
      years, suggests that metformin has many benefits in the treatment of these
      diseases. Metformin is a first-line drug in the treatment of overweight and obese
      type 2 diabetic patients, offering a selective pathophysiological approach by its
      effect on insulin resistance. Moreover, a number of studies have established the
      favorable effect of metformin on body weight, not only when evaluating BMI, but
      also if body mass composition is considered, through the reduction of fat mass.
      In addition, it reduces insulin resistance, hyperinsulinemia, lipid parameters,
      arterial hypertension and endothelial dysfunction. In particular, a new
      formulation of metformin extended-release (ER) is now available with different
      formulation in different countries. Metformin ER delivers the active drug through
      hydrated polymers which expand safe uptake of fluid, prolonging gastric transit
      and delaying drug absorption in the upper gastrointestinal tract. In addition,
      Metformin ER causes a small, but statistically significant decrease in BMI, when
      added to a lifestyle intervention program in obese adolescents. Because of the
      suggested benefits for the treatment of insulin resistance in many clinical
      conditions, besides type 2 diabetes, the prospective exists that more indications
      for metformin treatment are becoming a reality. 

PMID- 25069837
TI  - Psychometric properties of the Italian Yale Food Addiction Scale in overweight
      and obese patients.
AB  - AIM: To assess the dimensionality and psychometric properties of an Italian
      version of the Yale Food Addiction Scale (YFAS) in a sample of obese/overweight
      patients attending low-energy diet therapy. METHODS: Participants were 300
      overweight and obese patients who were admitted to a private medical center in
      Rome, Italy. Controls were 300 (231 women and 69 men) adults from the general
      population. All of the participants were administered the YFAS and the binge
      eating scale (BES). RESULTS: The one-factor model of the YFAS reported in
      previous studies did not fit the data chi(2)(209) = 466.69, p < 0.001, root mean
      square error of approximation (RMSEA) = 0.07; 90% CI: 0.06/0.08; comparative fit
      index (CFI) = 0.91; weighted root mean square residual (WRMR) = 1.40]. Through
      item analysis, it was suggested that five items (items #10, #11, #22, #24, and
      #25) with low item-total correlations should be removed from the measure. A 16
      item one-factor model revealed a better fit to the data (chi(2)(104) = 174.56; p
      < 0.001; RMSEA = 0.05; 90% CI: 0.04/0.07; CFI = 0.96), although the WRMR was
      slightly higher than that suggested as an indicator of good fit (WRMR = 1.01).
      The YFAS-16 had satisfactory internal consistency; it was able to discriminate
      obese patients from controls and strongly correlated with BES scores. CONCLUSION:
      The YFAS-16 assesses all of the "symptoms" represented in the original version
      and has satisfactory psychometric properties, although the percentage of food
      addiction diagnoses according to the YFAS-16 is lower than the percentage of
      diagnoses according to the original version of the questionnaire.

PMID- 25069838
TI  - Psychometric properties of the Italian Food Cravings Questionnaire-Trait-reduced
      (FCQ-T-r).
AB  - PURPOSE: The aim of the present study was to investigate dimensionality and
      psychometric properties of the Italian Food Cravings Questionnaire-Trait-reduced
      (FCQ-T-r) in a sample of obese and overweight patients seeking weight loss
      treatment. METHODS: Participants were 504 (416 women and 88 men) overweight and
      obese patients (BMI >= 25 kg/m(2)), and 289 (215 women and 74 men) Italian adults
      not currently seeking weight loss treatment. All participants were administered
      the Food Cravings Questionnaire-Trait (FCQ-T) and the Binge Eating Scale.
      RESULTS: The fifteen items included in the FCQ-T-r explained 93% of the variance
      of the 39-item FCQ-T total score (R(2) = 0.93). A principal axis factoring
      analysis indicated a one-factor solution, explaining 55.6% of the variance of the
      data. The FCQ-T-r had high internal consistency and was also able to
      differentiate between individuals with various severities of binge eating
      behavior. CONCLUSIONS: The FCQ-T-r may be considered a useful instrument for
      measuring trait food craving, when time constraints impede the use of the 39-item
      FCQ-T.

PMID- 25069839
TI  - ELM: enhanced lowest common ancestor based method for detecting a pathogenic
      virus from a large sequence dataset.
AB  - BACKGROUND: Emerging viral diseases, most of which are caused by the transmission
      of viruses from animals to humans, pose a threat to public health. Discovering
      pathogenic viruses through surveillance is the key to preparedness for this
      potential threat. Next generation sequencing (NGS) helps us to identify viruses
      without the design of a specific PCR primer. The major task in NGS data analysis
      is taxonomic identification for vast numbers of sequences. However, taxonomic
      identification via a BLAST search against all the known sequences is a
      computational bottleneck. DESCRIPTION: Here we propose an enhanced lowest-common
      ancestor based method (ELM) to effectively identify viruses from massive sequence
      data. To reduce the computational cost, ELM uses a customized database composed
      only of viral sequences for the BLAST search. At the same time, ELM adopts a
      novel criterion to suppress the rise in false positive assignments caused by the
      small database. As a result, identification by ELM is more than 1,000 times
      faster than the conventional methods without loss of accuracy. CONCLUSIONS: We
      anticipate that ELM will contribute to direct diagnosis of viral infections. The
      web server and the customized viral database are freely available at
      http://bioinformatics.czc.hokudai.ac.jp/ELM/.

PMID- 25069840
TI  - Progesterone and estradiol synergistically promote the lung metastasis of tuberin
      deficient cells in a preclinical model of lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a female-predominant lung disease that can lead
      to respiratory failure. LAM cells typically have inactivating tuberous sclerosis
      2 (TSC2) mutations, leading to mTORC1 hyperactivation. The gender specificity of
      LAM suggests that female hormones contribute to disease progression. Clinical
      findings indicate that estradiol exacerbates LAM behaviors and symptoms. Although
      hormonal therapy with progesterone has been employed, the benefit in LAM
      improvement has not been achieved. We have previously found that estradiol
      promotes the survival and lung metastasis of cells lacking tuberin in a
      preclinical model of LAM. In this study, we hypothesize that progesterone alone
      or in combination with estradiol promotes metastatic behaviors of TSC2-deficient
      cells. In cell culture models of TSC2-deficient LAM patient-derived and rat
      uterine leiomyoma-derived cells, we found that progesterone treatment or
      progesterone plus estradiol resulted in increased phosphorylation of Protein
      Kinase B (Akt) and Extracellular signal-regulated kinases1/2 (ERK1/2), induced
      the proliferation, and enhanced the migration and invasiveness. In addition,
      treatment of progesterone plus estradiol synergistically decreased the levels of
      reactive oxygen species and enhanced cell survival under oxidative stress. In a
      murine model of LAM, treatment of progesterone plus estradiol promoted the growth
      of xenograft tumors; however, progesterone treatment did not affect the
      development of xenograft tumors of Tsc2-deficient cells. Importantly, treatment
      of progesterone plus estradiol resulted in alteration of lung morphology and
      significantly increased the number of lung micrometastases of Tsc2-deficient
      cells compared with estradiol treatment alone. Collectively, these data indicate
      that progesterone increases the metastatic potential of Tsc2-deficient LAM
      patient-derived cells in vitro and lung metastasis in vivo. Thus, targeting
      progesterone-mediated signaling events may have therapeutic benefit for LAM and
      possibly other hormonally dependent cancers. 

PMID- 25069843
TI  - Brief reports: A distinct DNA methylation signature defines breast cancer stem
      cells and predicts cancer outcome.
AB  - Self-renewal and differentiation are two epigenetic programs that regulate stem
      cells fate. Dysregulation of these two programs leads to the development of
      cancer stem cells (CSCs). Recent evidence suggests that CSCs are relatively
      resistant to conventional therapies and responsible for metastasis formation.
      Deciphering these processes will help understand oncogenesis and allow the
      development of new targeted therapies. Here, we have used a whole genome promoter
      microarray to establish the DNA methylation portraits of breast cancer stem cells
      (bCSCs) and non-bCSCs. A total of 68 differentially methylated regions (DMRs)
      were more hypomethylated in bCSCs than in non-bCSCs. Using a differentiation
      assay we demonstrated that DMRs are rapidly hypermethylated within the first 6
      hours following induction of CSC differentiation whereas the cells reached the
      steady-state within 6 days, suggesting that these DMRs are linked to early CSC
      epigenetic regulation. These DMRs were significantly enriched in genes coding for
      TGF-beta signaling-related proteins. Interestingly, DMRs hypomethylation was
      correlated to an overexpression of TGF-beta signaling genes in a series of 109
      breast tumors. Moreover, patients with tumors harboring the bCSC DMRs signature
      had a worse prognosis than those with non-bCSC DMRs signature. Our results show
      that bCSCs have a distinct DNA methylation landscape with TGF-beta signaling as a
      key epigenetic regulator of bCSCs differentiation.

PMID- 25069842
TI  - The genetic impact of the lake chad basin population in North Africa as
      documented by mitochondrial diversity and internal variation of the L3e5
      haplogroup.
AB  - The presence of sub-Saharan L-type mtDNA sequences in North Africa has
      traditionally been explained by the recent slave trade. However, gene flow
      between sub-Saharan and northern African populations would also have been made
      possible earlier through the greening of the Sahara resulting from Early Holocene
      climatic improvement. In this article, we examine human dispersals across the
      Sahara through the analysis of the sub-Saharan mtDNA haplogroup L3e5, which is
      not only commonly found in the Lake Chad Basin (~17%), but which also attains
      nonnegligible frequencies (~10%) in some Northwestern African populations. Age
      estimates point to its origin ~10 ka, probably directly in the Lake Chad Basin,
      where the clade occurs across linguistic boundaries. The virtual absence of this
      specific haplogroup in Daza from Northern Chad and all West African populations
      suggests that its migration took place elsewhere, perhaps through Northern Niger.
      Interestingly, independent confirmation of Early Holocene contacts between North
      Africa and the Lake Chad Basin have been provided by craniofacial data from
      Central Niger, supporting our suggestion that the Early Holocene offered a
      suitable climatic window for genetic exchanges between North and sub-Saharan
      Africa. In view of its younger founder age in North Africa, the discontinuous
      distribution of L3e5 was probably caused by the Middle Holocene re-expansion of
      the Sahara desert, disrupting the clade's original continuous spread. 

PMID- 25069844
TI  - Vitamin D deficiency in the ICU: a systematic review.
AB  - In the last decade, few substances have been discussed as controversially as
      vitamin D. In the last few years, vitamin D research has now also found its way
      into the intensive care unit (ICU). Vitamin D deficiency is commonly found in the
      ICU and is associated with adverse outcomes including excess mortality, longer
      length of stay, higher sepsis incidence, longer mechanical ventilation. But how
      should one single vitamin be capable of such an impact? It has to be kept in mind
      that vitamin D is not a classic vitamin at all. It can be synthesized in
      sufficient amounts by the human body, it has a nuclear receptor and a large
      number of genes are under direct or indirect control of vitamin D. Furthermore,
      both the vitamin D receptor and the 1-alpha hydroxylase which is required to
      activate vitamin D are widely distributed in the human body. Unfortunately, as in
      other settings, a large body of observational data is opposed to only a few
      intervention studies. This article seeks to review the current observational and
      interventional literature concerning vitamin D status in the context of critical
      care, its effects on this highly vulnerable population and possible treatment
      strategies as well as an outlook on research that is necessary in the future. 

PMID- 25069841
TI  - Selective clearance of aberrant tau proteins and rescue of neurotoxicity by
      transcription factor EB.
AB  - Accumulating evidence implicates impairment of the autophagy-lysosome pathway in
      Alzheimer's disease (AD). Recently discovered, transcription factor EB (TFEB) is
      a molecule shown to play central roles in cellular degradative processes. Here we
      investigate the role of TFEB in AD mouse models. In this study, we demonstrate
      that TFEB effectively reduces neurofibrillary tangle pathology and rescues
      behavioral and synaptic deficits and neurodegeneration in the rTg4510 mouse model
      of tauopathy with no detectable adverse effects when expressed in wild-type mice.
      TFEB specifically targets hyperphosphorylated and misfolded Tau species present
      in both soluble and aggregated fractions while leaving normal Tau intact. We
      provide in vitro evidence that this effect requires lysosomal activity and we
      identify phosphatase and tensin homolog (PTEN) as a direct target of TFEB that is
      required for TFEB-dependent aberrant Tau clearance. The specificity and efficacy
      of TFEB in mediating the clearance of toxic Tau species makes it an attractive
      therapeutic target for treating diseases of tauopathy including AD. 

PMID- 25069845
TI  - Pituitary apoplexy: managing the life-threatening condition associated with
      pituitary adenomas.
AB  - Pituitary tumor apoplexy is one of a few life-threatening conditions in patients
      with pituitary adenomas. The very low incidence of this complication hinders
      formulation of widespread guidelines on diagnostic and therapeutic management.
      This article presents current opinions on epidemiology, risk factors, clinical
      signs and symptoms, also the difficulties in selecting appropriate therapeutic
      management. The paper has focused particularly on making decisions regarding
      surgical or conservative treatment in pituitary tumor apoplexy. Also the
      consequences of these decisions based on the key literature references. The
      article presents endocrine and neuro-ophthalmic consequences of previous
      pituitary tumor apoplexy with the key management principles for the follow-up
      period. 

PMID- 25069846
TI  - Adrenal dysfunction in critically ill children.
AB  - Cortisol is the major glucocorticoid synthesized by the adrenal cortex and its
      secretion is under the control of hypothalamic-pituitary axis. There is an
      increase in corticotrophin-releasing hormone and corticotrophin secretion and a
      decrease in the negative-feedback effect during critical illness. Adrenal
      insufficiency (AI) in children with critical illness is defined as an inadequate
      glucocorticoid response, measured by the peak cortisol or the increment in the
      cortisol level following exogenous ACTH (corticotrophin) administration.
      Clinically apparent AI is uncommon in critically ill patients. The incidence of
      AI in critically ill children varies with the underlying disease, its severity
      and duration, and multiple different definitions for the diagnosis of AI. Most of
      the pediatric studies for evaluation of AI during critical illness focused on
      patients with sepsis or septic shock. In patients with sepsis or septic shock,
      decreased synthesis or release of corticotrophin-releasing hormone,
      corticotrophin, and cortisol by cytokines and other circulating mediators
      released during sepsis are the most likely mechanism of AI. Recent studies in
      critically ill children reported that the prevalence of AI was not significantly
      different between septic and nonseptic patients, but it was noteworthy that AI
      appeared to be common both in septic and nonseptic critically ill children. A
      multidisplinary approach is necessary to manage to AI in critically ill children.
      However, no concensus exists among pediatric intensivist and endocrinologysts on
      diagnosis or treatment of AI in pediatric critical illness. 

PMID- 25069847
TI  - [Pleural mesothelioma. Cytology and molecular diagnostics].
AB  - The definitive diagnosis of malignant mesothelioma (MM) in effusion cytology is
      often avoided or reluctantly made by cytology alone. The most probable reason for
      this skepticism is the lack of expertise in cytology among many pathologists and
      clinicians. When an effusion specimen is composed of cells with unequivocal
      cytological features of malignancy that have the morphology and immunophenotype
      of mesothelial cells, the cytological diagnosis of MM is straightforward.
      However, in the daily routine difficult cases of atypical mesothelial cells are
      often encountered and additional methods are required to establish an accurate
      diagnosis. In contrast to reactive mesothelial cells cells of MMs often harbor
      chromosomal aberrations, most frequently a polysomy in combination with a 9p21
      deletion. These chromosomal aberrations can easily be detected by multitarget
      fluorescence in situ hybridization (FISH); therefore, FISH allows a reliable
      distinction between reactive mesothelial cells and MM cells. In order to be able
      to discriminate between MM and adenocarcinoma, an immunocytochemical panel
      consisting of different mesothelial and epithelial markers is very helpful. In
      most inconclusive cases of atypical mesothelial cells the combination of
      morphology, immunocytochemistry and FISH allows a better distinction between
      reactive mesothelial cells and MM in effusion cytology. 

PMID- 25069848
TI  - [Histological grading of epithelial ovarian cancer. Review and recommendation].
AB  - Histological grading of ovarian cancer has prognostic relevance and implications
      for treatment decisions. No standardized grading system has been established so
      far. Several grading systems are currently being used, including the FIGO, WHO,
      and Silverberg grading systems which cannot be directly translated into each
      other. Furthermore, individual grading criteria are not uniformly applicable to
      different histological subtypes. For serous ovarian cancer a binary grading
      system is now in use as the distinction between low-grade versus high-grade
      carcinomas reflects the different pathogenesis of these entities. Uniform
      guidelines for grading ovarian cancer are necessary and should ideally reflect
      the prognosis. This article provides an overview of commonly used grading systems
      and their prognostic value. The article demonstrates that a type-specific grading
      of ovarian cancer should be performed and recommendations for grading the various
      histological subtypes are given. 

PMID- 25069849
TI  - A new settlement for health and social care?

PMID- 25069850
TI  - Increased CDC20 expression is associated with development and progression of
      hepatocellular carcinoma.
AB  - Cell division cycle 20 (CDC20) encodes a regulatory protein interacting with the
      anaphase-promoting complex/cyclosome (APC/C) in the cell cycle and plays
      important roles in tumorigenesis and progression of multiple tumors. The present
      study aimed to investigate the clinical significance of CDC20 in hepatocellular
      carcinoma (HCC) and the role of CDC20 in the progression of HCC. By
      bioinformatics analysis, CDC20 was found to be the major node in HCC molecular
      interaction networks. Quantitative PCR and western blot analyses were applied to
      examine CDC20 expression in 16 paired primary HCC tissues. Immunohistochemistry
      (IHC) was performed to examine CDC20 protein expression in 132 matched paraffin
      embedded HCC tissues and to analyze the relationship between CDC20 staining and
      clinical characteristics. Small interfering RNA (siRNA) targeting CDC20 was
      synthesized and transfected into HepG2 cells to investigate the role of CDC20 in
      cell growth and the cell cycle. Results show that CDC20 expression was
      upregulated in HCC tissues compared to adjacent non-tumor liver tissues. In the
      132 matched HCC tissues, high expression levels of CDC20 were detected in 68.18%
      HCC samples, and overexpression of CDC20 was positively correlated with gender
      (P=0.013), tumor differentiation (P=0.000), TNM stage (P=0.012), P53 and Ki-67
      expression (P=0.023 and P=0.007, respectively). Cells transfected with CDC20
      siRNA showed a decrease in cell proliferation and increase in the number of cells
      in G2/M-phase. In conclusion, increased expression of CDC20 was demonstrated to
      be associated with the development and progression of HCC, and may be regarded as
      a promising therapeutic target for HCC. 

PMID- 25069851
TI  - Surgical retrieval of entrapped coronary angioplasty guidewire from the aorta.
AB  - An entrapped or retained coronary angioplasty guidewire is a rare but serious
      complication of coronary interventions. A failed percutaneous transluminal
      coronary angioplasty attempt on the left anterior descending artery in a 35-year
      old man was complicated by entrapment of the guidewire. Under cardiopulmonary
      bypass and cardioplegic arrest, the whole length of the entrapped guidewire was
      retrieved successfully from the left anterior descending artery and the aorta
      through an aortotomy following revascularization with left internal mammary
      artery. 

PMID- 25069852
TI  - Importance of time as a factor in the management of temporomandibular joint
      closed lock.

PMID- 25069853
TI  - Response to letter to the editor--Temporomandibular joint closed lock.

PMID- 25069854
TI  - Adeno-associated viral vectors show serotype specific transduction of equine
      joint tissue explants and cultured monolayers.
AB  - Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to
      sialic acid moieties present on cell surfaces. Abundance of the glycan profiles
      is greatly influenced by animal species, cell type, and culture conditions. The
      objective of this study was to determine whether AAV serotypes' transduction
      efficiencies specifically in the equine monolayer culture model are an accurate
      representation of transduction efficiencies in tissue explants, a model more
      closely related to in vivo transduction. It was found that AAV 2 and 2.5
      transduced cells more efficiently in explants than in monolayers. Through
      experiments involving assessing enzyme degradation of cell surface proteoglycans,
      this change could not be attributed to differences in the extra cellular matrix
      (ECM), but a similar change in AAV 5 transduction efficiency could be readily
      explained by differences in cell surface sialylated glycan. Unexpectedly it was
      found that in a small but diverse sample of horses evidence for serum
      neutralizing antibodies was only found to AAV 5. This suggests a unique
      relationship between this capsid and the equine host or an unresolved
      relationship between similar bovine AAV and the AAV 5 capsid immune response. 

PMID- 25069855
TI  - Development of an iron-enriched high-yieldings indica rice cultivar by
      introgression of a high-iron trait from transgenic iron-biofortified rice.
AB  - Low level of iron in staple food crops is one reason for the predominance of iron
      deficiency anemia in developing countries. Most of the iron in rice grains
      accumulates in the outer aleurone layer and embryo, which are removed during
      milling, and the edible endosperm contains very low amounts of iron. In an effort
      to increase iron nutrition, we report here the transgene introgression of a high
      iron trait into a high-yielding indica rice cultivar. The ferritin gene from
      soybean (soyfer1) was introduced into rice plants through interbreeding between
      soybean ferritin-overexpressing transgenic IR68144 and the high-yielding cultivar
      Swarna. The stable integration of the soyfer1 gene was confirmed in the BC2F4
      generation, and the hybrid seeds showed 2.6-fold soybean ferritin gene expression
      over the recurrent parent Swarna. The hybrid milled seeds revealed a 2.54-fold
      increase in iron and 1.54-fold increase in zinc compared to Swarna. Agronomic
      data and an SSR marker analysis of the hybrid rice plants were taken into account
      for NIL character identification. 

PMID- 25069856
TI  - Effect of electric field treatment on unsaturated fatty acid in crude avocado
      oil.
AB  - The objective of this study was to evaluate the stability of the fatty acids in
      avocado oil when the product is subjected to different conditions of electric
      field treatment (voltage: 5 kV cm(-1); frequency: 720 Hz; treatment time: 5, 10,
      15, 20, and 25 min). Fatty acids were analyzed by Fourier transform infrared
      spectroscopy in the mid-infrared region. Electric field is a suitable method to
      preserve the oil quality and composition with minimal modifications in
      unsaturated fatty acids.

PMID- 25069857
TI  - Ultrasonographic and anatomic study of the canine elbow joint.
AB  - OBJECTIVE: To (1) assess the canine elbow joint using a high frequency transducer
      (18 MHz); (2) describe the echogenicity and echo texture of the joint; and (3)
      correlate the ultrasonographic images with transparent plastinated anatomic
      sections. DESIGN: Descriptive study. SAMPLE POPULATION: German Shepherd cross
      breed dogs (cadavers, n = 10; live dogs, n = 5). METHODS: Elbow joints of 10
      adult German Shepherd cross-breed dog cadavers were examined by ultrasonography
      and then 5 cadavers were selected for use in an anatomic study, in which 2 mm
      thick sections were obtained in the same planes as in the ultrasonographic
      protocol. Sections were plastinated using the E-12 plastination method and
      correlated to the corresponding ultrasonographic images. The elbow joints of 5
      German Shepherd adult dogs were assessed by ultrasonography for comparison with
      cadaver images. RESULTS: Good correspondence of soft tissue and bone structures
      was obtained between ultrasound images and anatomic sections. There was no
      difference in the ultrasonographic appearance of elbows of cadavers and live dogs
      in which the muscular, ligamentous, and bone components of the joints were
      evaluated. CONCLUSION: This study presents a descriptive comparison of anatomic
      and ultrasonographic images, which will offer clinicians a more comprehensive
      understanding of the anatomic structures of the canine elbow joint and serve as
      reference for further imaging diagnostic studies because of the precise
      correspondence between anatomic plastinated sections and ultrasonographic images.

PMID- 25069858
TI  - Activation of autophagy by rapamycin does not protect oligodendrocytes against
      protein aggregate formation and cell death induced by proteasomal inhibition.
AB  - Pathological protein inclusions containing the microtubule-associated protein
      tau, ubiquitin, and a variety of heat shock proteins, originating in
      oligodendrocytes, are consistent features observed in a number of
      neurodegenerative diseases. Defects in the proteolytic degradation systems have
      been associated with protein aggregate formation. The ubiquitin proteasome system
      (UPS) and autophagy are critically involved in the maintenance of cellular
      homeostasis and their activities need to be carefully balanced. A genuine
      crosstalk exists between the UPS and the autophagosomal system, and when the UPS
      is impaired, autophagy might act as a compensatory mechanism. Autophagy
      represents a lysosomal degradation system for degrading long-lived proteins and
      organelles, including damaged mitochondria. As we have shown before, proteasomal
      impairment by the reversible proteasomal inhibitor MG-132 (carbobenzoxy-L-leucyl
      L-leucyl-L-leucinal) in oligodendrocytes leads to protein aggregate formation and
      apoptotic cell death, caused by activation of caspases and the mitochondrial
      pathway. The present study was undertaken to elucidate whether upregulation of
      the autophagic pathway by rapamycin can protect oligodendrocytes and ameliorate
      the consequences of MG-132-induced protein aggregate formation. The data show
      that rapamycin attenuated the formation of dense protein aggregates, but did not
      enhance the survival capability of oligodendrocytes after proteasomal inhibition.
      After activation of the autophagic pathway in combination with proteasomal
      inhibition, caspase 3 activation and poly(ADP-ribose) polymerase-1 cleavage were
      even more pronounced than after proteasomal inhibition alone. Furthermore,
      rapamycin augmented MG-132-induced activation of extracellular signal-regulated
      kinases 1 and 2, which are involved in the regulation of cell death and survival.
      In summary, depending on the cellular context and system, rapamycin may promote
      cell survival or, under other conditions in concert with apoptosis, may augment
      cell death, which seems to be the case in oligodendrocytes. Its therapeutic use
      for neurodegenerative disorders is most likely limited, since long-term
      administration may impair neuronal survival and specifically damage the myelin
      forming cells of the CNS. 

PMID- 25069859
TI  - Comparison of [(99m)Tc]tilmanocept and filtered [(99m)Tc]sulfur colloid for
      identification of SLNs in breast cancer patients.
AB  - BACKGROUND: The efficacy of sentinel lymph node (SLN) surgery requires targeted
      removal of first-draining nodes; however, frequently more nodes are removed than
      necessary. [(99m)Tc]tilmanocept (TcTM) is a molecular-targeted
      radiopharmaceutical specifically designed for SLN mapping. We evaluated technical
      outcomes of SLN biopsy in breast cancer patients mapped with TcTM + vital blue
      dye (VBD) versus filtered [(99m)Tc]sulfur colloid (fTcSC) + VBD. METHODS: There
      were 84 versus 115 patients in the TcTM versus fTcSC cohorts, respectively. Main
      measures were the number of SLNs removed per patient and factors influencing
      number of nodes removed. We also evaluated whether the radiotracer injected
      affected the proportion of positive nodes removed in node-positive patients.
      RESULTS: Fewer nodes were removed among patients mapped with TcTM compared to
      fTcSC (mean TcTM: 1.85 vs. fTcSC: 3.24, p < 0.001). Logistic regression analysis
      adjusted for tumor characteristics showed that injection of fTcSC (p < 0.001)
      independently predicted removal of greater than 3 nodes. A similar proportion of
      patients was identified as node-positive, whether mapped with TcTM or with fTcSC
      (TcTM: 24 % vs. fTcSC: 17 %, p = 0.3); however, TcTM detected a greater
      proportion of positive nodes among node-positive patients compared with fTcSC
      (0.73 vs. 0.43, p = 0.001). CONCLUSIONS: Patients undergoing SLN biopsy with TcTM
      required fewer SLNs to identify the same rate of node-positive patients compared
      with fTcSC in breast cancer patients with similar risk of axillary metastatic
      disease. These data suggest that a molecularly targeted mechanism of SLN
      identification may reduce the total number of nodes necessary for accurate
      axillary staging.

PMID- 25069860
TI  - Treatment patterns and outcomes for patients with adrenocortical carcinoma
      associated with hospital case volume in the United States.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare, aggressive disease with no
      apparent change in treatment or survival in the United States over the past two
      decades. Our objective was to determine whether treatment patterns or clinical
      outcomes vary by hospital case volume. METHODS: Patients with ACC were identified
      from the National Cancer Database (1998-2011). High-volume centers (HVCs) were
      defined by a case load of >=4 cases of primary adrenal malignancy annually, which
      corresponded to the 90th percentile. All other facilities were considered low
      volume centers (LVCs). RESULTS: A total of 2,765 ACC patients were treated across
      1,046 facilities. Compared to patients treated at LVCs, patients treated at HVCs
      were younger (50 vs. 54 years), with larger tumors (11.2 vs. 10.5 cm), and
      underwent higher rates of surgery (78.8 vs. 73.4 %), radical resection (17.3 vs.
      13.9 %), regional lymph node evaluation (23.2 vs. 18.8 %), and chemotherapy
      including mitotane (43.8 vs. 31.0 %, all p < 0.05).There were no significant
      differences in median length of stay (5 vs. 5 days), 30-day readmission rates
      (4.0 % for HVCs vs. 3.9 % for LVCs), or 30-day postoperative mortality rates (1.9
      % for HVCs vs. 3.7 % for LVCs). Median overall survival was 2.0 years for HVCs
      and 1.9 years for LVCs, p = 0.53. After adjusting for patient and tumor
      characteristics, overall survival did not differ significantly between patients
      treated at HVCs versus LVCs [HR = 0.89 (95 % confidence interval 0.70, 1.12)].
      CONCLUSIONS: Treatment at HVCs was associated with more aggressive surgical
      resection and chemotherapy use. Prognosis remained poor despite more aggressive
      treatment.

PMID- 25069861
TI  - Epithelial-to-mesenchymal transition (EMT) in intraductal papillary mucinous
      neoplasm (IPMN) is associated with high tumor grade and adverse outcomes.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is generally associated
      with increased tumor aggressiveness and poor prognosis. We evaluated EMT
      characteristics in intraductal papillary mucinous neoplasm (IPMN) tumor specimens
      and their potential role as biomarkers for malignancy, metastasis, and adverse
      patient outcomes. METHODS: IPMN surgical specimens were identified and reviewed
      by two gastrointestinal pathologists. Immunohistochemical analysis of E-cadherin,
      vimentin, and ZEB-1 was performed. Samples were linked to clinicopathologic and
      outcome data for these patients. Western blot test was used to evaluate ZEB-1
      expression in IPMN samples; 846 human miRNAs were profiled, and EMT-related
      differentially expressed miRNAs were validated using quantitative real-time
      polymerase chain reaction. RESULTS: Fifty-eight IPMN specimens and five normal
      pancreatic tissue samples were immunohistochemically stained and scored. E
      cadherin expression was significantly lower in malignant versus low-grade IPMN (p
      < 0.05). Vimentin expression was increased in malignant IPMN tumor samples (p <
      0.05). EMT was associated with increased lymph node metastasis and decreased
      survival of malignant IPMN patients (p < 0.05). ZEB-1, an imperative EMT
      regulator, was exclusively expressed by malignant IPMN tumors. miRNA hierarchical
      clustering demonstrated grouping of two main IPMN subgroups: low-grade IPMN
      versus high-grade IPMN and carcinoma. Twenty-four miRNAs were differentially
      expressed (14 up-regulated, 10 down-regulated). The EMT-regulatory miRNAs, miR
      200c and miR-141, were down-regulated (twofold and 1.8-fold decrease,
      respectively) in malignant versus low-grade IPMN (p < 0.05). CONCLUSIONS: EMT may
      play a role in IPMN tumorigenesis and metastasis. EMT molecular deregulations
      could be utilized as potential novel biomarkers for the identification of high
      risk IPMN patients.

PMID- 25069862
TI  - Flow cytometric evaluation of the safety of intraoperative salvaged blood
      filtered with leucocyte depletion filter in spine tumour surgery.
AB  - BACKGROUND: Intraoperative cell salvage (IOCS) has not been widely adopted in
      oncological surgery due to the hypothetical concern of reinfusion of malignant
      cells. We evaluated the feasibility of IOCS in combination with leucocyte
      depletion filter (LDF) in metastatic spine tumour surgery (MSTS). METHODS:
      Patients with known primary epithelial tumour, operated for metastatic spinal
      disease, were recruited. Blood samples were collected at five different stages
      during surgery: 2 stages from patient vein during induction and at the time of
      maximum tumour manipulation, 3 stages from the operative blood prior to IOCS
      processing, after IOCS processing, and after IOCS-LDF processing. Of the samples
      taken at each stage, 5 ml were analyzed for tumour cells using flow cytometry.
      RESULTS: Of 12 patients recruited, only 11 could be finally analyzed. Flow
      cytometry analysis of their samples showed that 8 of 11 patients had tumour cells
      in the unfiltered salvaged blood. In filtered salvaged blood, the tumour cell
      count was zero in the majority of samples (8/11 patients), whereas three
      patients' samples had a few tumour cells. The mean difference between the tumour
      cell quantity in the samples from the patient vein and filtered salvaged blood
      was significant. CONCLUSIONS: IOCS-LDF was shown to be effective in removing
      tumour cells from the blood salvaged during MSTS. If there were any tumour cells
      found, the quantity was significantly less than that in the patient's
      circulation. The results of this study reiterates the conclusions of our previous
      published work where we showed that IOCS-LDF treated blood in MSTS is safe for
      transfusion.

PMID- 25069863
TI  - A late, solitary brain metastasis of epithelial ovarian carcinoma.
AB  - BACKGROUND: Brain metastasis from epithelial ovarian cancer (EOC) is very rare
      with a reported incidence of less than 2%. It is usually associated with a poor
      prognosis that is related to several factors, the most important including:
      single vs multiple lesions, performance status, platinum-sensitive disease, tumor
      grade, extracranial disease, and multimodal approach treatment. At the time of
      diagnosis, an extracranial disease is found in over half of patients. The most
      common histology is the serous type. The median time from primary diagnosis to
      development of cerebral lesions is directly correlated to initial tumor grade and
      stage. Several therapeutic approaches can be proposed, including best supportive
      care +/- corticosteroids, surgery, radiotherapy and chemotherapy. A multimodal
      therapy approach may achieve an improved outcome and should therefore be utilized
      whenever applicable. CASE PRESENTATION: We present the case of a patient with a
      solitary brain metastasis which appeared 11 years after a locally advanced and
      aggressive EOC (FIGO stage III C) and which totally regressed after surgery and
      adjuvant chemotherapy. Clinically, she showed progressive headaches, decreased
      visual acuity, balance and memory disorders associated with a confusional state.
      Brain CT scan and MRI documented a solitary, necrotic lesion in the left central
      parietal region with an important cerebral surrounding edema and initial cranial
      herniation. No other extracranial metastases were observed at the PET scan.
      Laboratory tests were in the normal range and CA 125 was moderatly increased at
      81 UI/ml. The patient underwent surgical removal of tumor lesion, post-surgical
      whole-brain radiotherapy (WBRT) and systemic chemotherapy with carboplatin alone
      for six cycles. At a follow-up of 13 months, she is alive, in good clinical
      condition and tumor progression free. CONCLUSION: The peculiarity of this case
      relies on the isolated brain relapse of a BRCA-1/BRCA-2 non-mutated EOC, which is
      uncommon and rare, and to the very long time, of 11 years, from diagnosis of
      primary cancer and development of brain metastasis. A multimodal, aggressive
      approach of this isolated brain metastasis led to a complete and prolonged tumor
      control.

PMID- 25069864
TI  - Fatigue correlates with the decrease in parasympathetic sinus modulation induced
      by a cognitive challenge.
AB  - BACKGROUND: It is known that enhancement of sympathetic nerve activity based on a
      decrease in parasympathetic nerve activity is associated with fatigue induced by
      mental tasks lasting more than 30 min. However, to measure autonomic nerve
      function and assess fatigue levels in both clinical and industrial settings,
      shorter experimental durations and more sensitive measurement methods are needed.
      The aim of the present study was to establish an improved method for inducing
      fatigue and evaluating the association between it and autonomic nerve activity.
      METHODS: Twenty-eight healthy female college students participated in the study.
      We used a kana pick-out test (KPT) as a brief verbal cognitive task and recorded
      electrocardiography (ECG) to measure autonomic nerve activity. The experimental
      design consisted of a 16-min period of ECG: A pre-task resting state with eyes
      open for 3 min and eyes closed for 3 min, the 4-min KPT, and a post-task resting
      state with eyes open for 3 min and eyes closed for 3 min. RESULTS: Baseline
      fatigue sensation, measured by a visual analogue scale before the experiment, was
      associated with the decrease in parasympathetic sinus modulation, as indicated
      the by ratio of low-frequency component power (LF) to high-frequency component
      power (HF), during the KPT. The LF/HF ratio during the post-KPT rest with eyes
      open tended to be greater than the ratio during the KPT and correlated with
      fatigue sensation. Fatigue sensation was correlated negatively with log
      transformed HF, which is an index of parasympathetic sinus modulation, during the
      post-KPT rest with eyes open. CONCLUSIONS: The methods described here are useful
      for assessing the association between fatigue sensation and autonomic nerve
      activity using a brief cognitive test in healthy females.

PMID- 25069866
TI  - Biocontainment laboratories: addressing the terror within.

PMID- 25069865
TI  - Molecular modeling application on hapten epitope prediction: an enantioselective
      immunoassay for ofloxacin optical isomers.
AB  - To deepen our understanding of the physiochemical principles that govern hapten
      antibody recognition, ofloxacin enantiomers were chosen as a model for epitope
      prediction of small molecules. In this study, two monoclonal antibodies (mAbs)
      mAb-WR1 and mAb-MS1 were raised against R-ofloxacin and S-ofloxacin,
      respectively. The enantioselective mAbs have a high sensitivity and specificity,
      and the enantioselectivity is not affected by heterologous coating format
      reactions. The epitopes of the ofloxacin isomers were predicted using the
      hologram quantitative structure-activity relationship (HQSAR) and comparative
      molecular field analysis (CoMFA) approaches. The results consistently show that
      the epitope of the chiral hapten should be primarily composed of the oxazine ring
      and the piperazinyl ring and mAbs recognize the hapten from the side of this
      moiety. The enantioselectivity of mAbs is most likely due to the steric hindrance
      caused by the stereogenic center of the epitope. Modeling of chiral hapten
      protein mimics reveals that ofloxacin isomers remain upright on the surface of
      the carrier protein. Suggestions to improve the enantioselectivity of antibodies
      against ofloxacin isomers were also proposed. This study provided a simple,
      efficient, and general method for predicting the epitopes of small molecules via
      molecular modeling. The epitope predictions for small molecules may create a
      theoretical guide for hapten design. 

PMID- 25069867
TI  - Space requirement of a prefabricated bar on two interforaminal implants: a
      prospective clinical study.
AB  - OBJECTIVES: This clinical study measured the dimensional changes of existing
      lower complete dentures due to the integration of a prefabricated implant bar.
      Additionally, the impact of this dimensional change on patient satisfaction and
      oral function was analyzed. METHODS: Twenty edentulous patients (10 men/10 women;
      aged 65.9 +/- 11.8 years) received two interforaminal implants. Subsequent to
      surgery, a chair side adapted, prefabricated bar (SFI Bar((r)), C+M, Biel,
      Switzerland) was inserted, and the matrix was polymerized into the existing lower
      denture. The change of the denture's lingual dimension was recorded by means of a
      bicolored, silicone denture duplicate that was sectioned in the oro-vestibular
      direction in the regions of the symphysis (S) and the implants (I-left, I-right).
      On the sections, the dimensional increase was measured using a light microscope.
      Six months after bar insertion, patients answered a standardized questionnaire.
      RESULTS: All dentures exhibited increased lingual volume, more extensively at S
      than at I (P = 0.001). At S, the median diagonal size of the denture was doubled
      (+4.33 mm), and at I, the median increase was 50% (I-left/-right = +2.66/+2.62
      mm). The original denture size influenced the volume increase (P = 0.024):
      smaller dentures led to a larger increase. The amount of denture increase did not
      have negative impact on either self-perceived oral function or patient
      satisfaction. Approximately, 95% of the patients were satisfied with the
      treatment results. CONCLUSIONS: The lingual size of a lower denture was enlarged
      by the integration of a prefabricated bar without any negative side effects.
      Thus, this attachment system is suitable to convert an existing full denture into
      an implant-supported overdenture.

PMID- 25069868
TI  - The impact of the meningococcal serogroup C conjugate vaccine in Canada between
      2002 and 2012.
AB  - BACKGROUND: Before 2001, the incidence of invasive meningococcal disease (IMD) in
      Canada was 1.0 per 100 000 per year, with 40% of cases caused by serogroup C
      organisms. During 2001-2005 all provinces introduced the meningococcal serogroup
      C conjugate vaccine (MCCV) into their routine infant immunization schedule.
      METHODS: Active, prospective, population-based surveillance of IMD in children
      and adults was conducted by the Canadian Immunization Monitoring Program, ACTive
      (IMPACT) during 2002-2012. Inclusion criteria were admission to hospital and
      identification of Neisseria meningitidis from a sterile site. Incidence was
      estimated using population census data from Statistics Canada. RESULTS: Prior to
      MCCV introduction, serogroup C disease incidence was 0.07-0.25 per 100 000 per
      year depending on the province. Following vaccine introduction, serogroup C
      disease decreased to <0.05 per 100 000 per year, with a reduction of 14% per year
      (P = .0014). A decrease occurred in all provinces, despite differing schedules
      being implemented. The largest decrease of 83% (from 0.27 to 0.05 per 100 000 per
      year) occurred in the 15-24 year age group (P = .0100) who were not vaccinated in
      all provinces. There was no impact on the incidence of nonserogroup C disease
      over the same period (P = .9811). CONCLUSIONS: MCCV dramatically reduced the
      incidence of serogroup C IMD in Canada through both direct and indirect effects.
      The observation that disease incidence decreased with different schedules
      suggests that the doses at 12 months (common to all provinces) and adolescence (7
      of 8 provinces studied) were critical in achieving disease control.

PMID- 25069869
TI  - A decade of herd protection after introduction of meningococcal serogroup C
      conjugate vaccination.
AB  - BACKGROUND: Vaccination with meningococcal serogroup C (MenC) conjugate (MCC)
      polysaccharide vaccines led to a substantial decline in MenC disease in the
      vaccinated and the unvaccinated population. The decline in the unvaccinated
      population can be explained by herd protection by reduced colonization of
      meningococci expressing the MenC capsule. The duration of such herd protection is
      unknown. METHODS: In a nationwide study from the Netherlands, we compared MenC
      invasive disease between 1998 and the introduction of MCC vaccination (2002) with
      that from 2002 to 2012, in age groups eligible and not eligible for vaccination.
      The proportions of isolates from clonal complexes with high serogroup C capsule
      expression rate during carriage (sequence type [ST] 11 and ST-8 complex) was
      compared between the pre- and postvaccination periods. RESULTS: A total of 814
      patients with invasive MenC disease were included for analysis. There was a 99%
      decline in MenC disease in patients eligible for vaccination and a 93% decline in
      those not eligible. Thirty-six percent of the overall MenC reduction between the
      first and last 4 years of the observation period occurred in the unvaccinated
      population. Clonal complex was determined in 350 (43%) isolates. The proportion
      of cases caused by clonal complex ST-11 and ST-8 serogroup C meningococci
      decreased from 251 of 268 (94%) before, to 46 of 57 (81%) after MCC vaccine
      introduction (P = .004). CONCLUSIONS: Our findings provide further evidence that
      herd protection results from reduced carriage of virulent meningococci. Herd
      protection was responsible for >36% of MCC vaccine impact and lasted for >=10
      years.

PMID- 25069870
TI  - Editorial commentary: fifteen years of protection by meningococcal C conjugate
      vaccines: lessons from disease surveillance.

PMID- 25069871
TI  - Patterns of tobacco smoking among illicit drug users in Australia 2001-2010.
AB  - INTRODUCTION AND AIMS: This study aimed to investigate whether there were changes
      from 2001 to 2010 in the characteristics of young adults who used party drugs or
      other illicit drugs and to determine if the prevalence of tobacco smoking
      differed depending on the type of drugs used. DESIGN AND METHODS: We analysed
      confidentialised data from the 2001 and 2010 National Drug Strategy Household
      Surveys. We compared young adults (aged 18-29) who used party drugs to other drug
      users and non-users on demographic variables. We assessed relationships between
      (i) illicit drug use and smoking; (ii) illicit drug use and smoking while
      controlling for social and demographic differences; and (iii) illicit drug use
      and smoking after controlling for social and demographic variables along with
      cannabis and alcohol use. RESULTS: There was little difference between 2001 and
      2010 in drug user characteristics and smoking. Party drug users were more
      educated and of higher socioeconomic status than illicit drug users and non
      users. Party drug users and users of other illicit drugs were far more likely to
      smoke tobacco; however, a large part of this relationship was explained by the
      higher rate of cannabis and alcohol use in these groups. DISCUSSION AND
      CONCLUSIONS: Over the last decade, party drug users have been a relatively
      socially advantaged sub-population, yet smoking prevalence among these and other
      drug users has remained higher than among non-users. This might be explained by
      the common sequence of drug involvement in which people initiate smoking, then
      cannabis use and followed by other drugs.

PMID- 25069872
TI  - Ficolins and the lectin pathway of complement in patients with systemic lupus
      erythematosus.
AB  - The complement system plays a pathophysiological role in systemic lupus
      erythematosus (SLE). This study aims to investigate whether an association exists
      between the ficolins that are part of the lectin complement pathway and SLE. EDTA
      plasma samples from 68 Danish SLE patients and 29 healthy donors were included in
      the study. Plasma concentrations of Ficolin-1, -2, and -3 were determined in
      specific sandwich ELISAs. Lectin pathway activity via Ficolin-3 was measured in
      ELISA on acetylated bovine serum albumin (acBSA) and measured as Ficolin-3
      binding and deposition of C4, C3 and the terminal complement complex (TCC). SLE
      patients had increased levels of Ficolin-3, 21.6MUg/ml as compared to 17.0MUg/ml
      in healthy controls (P=0.0098). The Ficolin-1 plasma concentration was negatively
      correlated with SLE Disease Activity Index (SLEDAI) (Rho=-0.29, P=0.015) and
      positively correlated to the [Systemic Lupus International Collaborating Clinics
      (SLICC)/American College of Rheumatology (ACR) Damage Index] (SDI) (Rho=0.27,
      P=0.026). The Ficolin-1 concentration was also associated with the occurrence of
      arterial (P=0.0053) but not venous thrombosis (P=0.42). Finally, deposition of
      C4, C3 and TCC in the Ficolin-3 pathway were all correlated to SLEDAI,
      respectively (P<0.0076). The Ficolin-1 association to SLEDAI and SDI as well as
      arterial thrombosis shown in this study suggests that Ficolin-1 may be a
      potential new biomarker for patients with SLE. Furthermore, Ficolin-3 mediated
      complement activation may be valuable in monitoring disease activity in SLE
      patients due to the high sensitivity for complement consumption in the assay
      independent of the Ficolin-3 concentration. 

PMID- 25069873
TI  - Effects of stimulation frequency and intensity in sacral neuromodulation on
      anorectal inputs to the somatosensory cortex in an experimental model.
AB  - INTRODUCTION: Although sacral neuromodulation (SNM) is an established treatment
      for faecal incontinence, stimulation parameters have been derived empirically and
      only one frequency (14 Hz) is employed clinically. The aim of this study was to
      test a range of stimulation frequencies to establish an optimal frequency of SNM
      for maximum augmentation of anal canal cortical evoked potentials (EPs) in an
      animal model. METHODS: In female Wistar rats, anal canal EPs were recorded over
      the primary somatosensory cortex using a flexible multielectrode array, and the
      effect of SNM was studied. SNM was applied at 0.1-100 Hz and a frequency response
      curve plotted. The data were fitted to a quadratic equation. RESULTS: The
      magnitude of potentiation of anal canal EPs caused by SNM depended significantly
      on stimulation frequency (P < 0.001). The frequency-potentiation relationship was
      parabolic in form, with a clear optimum at 2 Hz. The SNM must be applied for at
      least 3 min. The theoretical maximal potentiation predicted by the model was not
      found to be statistically different to actual data recorded (P = 0.514-0.814).
      The response depended on stimulation amplitude in an 'all-or-nothing' fashion.
      EPs were augmented when the SNM intensity was 0.5 times the motor threshold to
      tail twitch or greater, but values below this intensity failed to affect the EPs.
      CONCLUSION: The effect of SNM in this animal model is governed principally by
      frequency, with an optimum of 2 Hz. If animal data can be translated to humans,
      optimization of SNM frequency may offer a clinically relevant improvement in the
      efficacy of SNM. Surgical relevance Sacral neuromodulation (SNM) for faecal
      incontinence currently employs stimulation parameters that have been derived
      empirically and may not be optimal. This study used an animal model of SNM and
      focused on its acute effect on anal canal cortical evoked potentials (EPs). It
      was found that SNM potentiated EPs, with a clear optimum at a frequency of 2 Hz.
      If this finding is applicable to the mechanism of action of human SNM, this
      suggests that there may be a clinically relevant improvement by reducing stimulus
      frequency from its typical value of 14 Hz to 2 Hz.

PMID- 25069874
TI  - Gleditsia sinensis thorn extract inhibits the proliferation and migration of PDGF
      induced vascular smooth muscle cells.
AB  - The thorns of Gleditsia sinensis have been used to prevent or treat numerous
      diseases. The present study aimed to investigate the molecular mechanism of the
      ethanol extract of Gleditsia sinensis thorns (EEGS) on platelet-derived growth
      factor (PDGF)-treated vascular smooth muscle cells (VSMCs). EEGS treatment was
      found to inhibit DNA synthesis in PDG?F-treated VSMCs in a dose-dependent manner,
      without cell toxicity. These inhibitory effects were associated with G1-phase
      cell-cycle arrest, which was caused by the decreased expression of cyclins and
      cyclin-dependent kinases (CDKs) and the upregulation of p27KIP1 expression in
      PDGF-stimulated VSMCs. Among the pathways examined, EEGS treatment was observed
      to only inhibit the PDGF-induced phosphorylation of Akt. In addition, EEGS
      treatment suppressed the migration and invasion of VSMCs in the presence of PDGF
      as determined by wound-healing and MatrigelTM invasion assays. Furthermore,
      zymographic and western blot analyses revealed that EEGS treatment suppressed
      matrix metalloproteinase (MMP)-9 expression in PDGF-treated VSMCs, which was
      attributed to a reduction in the binding activities of nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB), activator protein (AP)-1 and
      specificity protein (Sp)-1. These results demonstrate that EEGS induces p27KIP1
      mediated G1-phase cell-cycle arrest, reduces Akt phosphorylation and prevents MMP
      9 expression by decreasing the binding activities of NF-kappaB, AP-1 and Sp-1 in
      PDGF-treated VSMCs, thus resulting in growth inhibition and the suppression of
      migration and invasion. These results may suggest a novel perspective for the use
      of EEGS in the treatment and prevention of vascular proliferative diseases.

PMID- 25069875
TI  - Genome-wide comprehensive analysis of transcriptional regulation by ArgR in
      Thermus thermophilus.
AB  - ArgR is known to serve as a repressor/activator of the metabolism of arginine. To
      elucidate the role of ArgR in the metabolism of Thermus thermophilus cells,
      comparative genome-wide comprehensive analysis was conducted for wild-type T.
      thermophilus and its mutant lacking the argR gene. Transcriptome analysis and
      chromatin affinity precipitation coupled with high-density tiling chip (ChAP
      chip) analysis identified 34 genetic loci that are directly regulated by ArgR and
      indicated that ArgR decreases the expression of arginine biosynthesis and also
      regulates several other genes involved in amino acid metabolism, including lysine
      biosynthetic genes, as suggested by our previous study. Among genes whose
      expression was regulated by ArgR, the largest effect of argR knockout was
      observed in a putative operon, including genes TTHA0284, TTHA0283, and TTHA0282
      involved in arginine biosynthesis. The promoter of this operon, argG, was
      repressed approximately 21-fold by ArgR. DNase I footprint analysis coupled with
      electrophoretic mobility shift assay suggested that high arginine-dependent
      repression was attributed to the fact that the promoter contains three operators
      for ArgR binding and ArgR is bound to the binding sites cooperatively, possibly
      forming a DNA loop, in the hexameric form stabilized by arginine binding.

PMID- 25069876
TI  - Purification and characterization of a cold-adapted pullulanase from a
      psychrophilic bacterial isolate.
AB  - There is a considerable potential of cold-active biocatalysts for versatile
      industrial applications. A psychrophilic bacterial strain, Shewanella arctica 40
      3, has been isolated from arctic sea ice and was shown to exhibit pullulan
      degrading activity. Purification of a monomeric, 150-kDa pullulanase was achieved
      using a five-step purification approach. The native enzyme was purified 50.0-fold
      to a final specific activity of 3.0 U/mg. The enzyme was active at a broad range
      of temperature (10-50  degrees C) and pH (5-9). Optimal activity was determined
      at 45  degrees C and pH 7. The presence of various metal ions is tolerated by the
      pullulanase, while detergents resulted in decreased activity. Complete conversion
      of pullulan to maltotriose as the sole product and N-terminal amino acid sequence
      indicated that the enzyme is a type-I pullulanase and belongs to rarely
      characterized pullulan-degrading enzymes from psychrophiles.

PMID- 25069877
TI  - Functional transient receptor potential vanilloid 1 and transient receptor
      potential vanilloid 4 channels along different segments of the renal vasculature.
AB  - AIM: Transient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4)
      cation channels have been recently identified to promote endothelium-dependent
      relaxation of mouse mesenteric arteries. However, the role of TRPV1 and TRPV4 in
      the renal vasculature is largely unknown. We hypothesized that TRPV1/4 plays a
      role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We
      studied the distribution of functional TRPV1/4 along different segments of the
      renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS:
      The TRPV1 agonist capsaicin relaxed mouse mesenteric arteries with an EC50 of 25
      nm, but large mouse renal arteries or rat descending vasa recta only at >100-fold
      higher concentrations. The vasodilatory effect of capsaicin in the low-nanomolar
      concentration range was endothelium-dependent and absent in vessels of Trpv1 -/-
      mice. The TRPV4 agonist GSK1016790A relaxed large conducting renal arteries,
      mesenteric arteries and vasa recta with EC50 of 18, 63 nm and ~10 nm
      respectively. These effects were endothelium-dependent and inhibited by a TRPV4
      antagonist, AB159908 (10 MUm). Capsaicin and GSK1016790A produced vascular
      dilation in isolated mouse perfused kidneys with EC50 of 23 and 3 nm
      respectively. The capsaicin effects were largely reduced in Trpv1 -/- kidneys,
      and the effects of GSK1016790A were inhibited in Trpv4 -/- kidneys. CONCLUSION:
      Our results demonstrate that two TRPV channels have unique sites of
      vasoregulatory function in the kidney with functional TRPV1 having a narrow,
      discrete distribution in the resistance vasculature and TRPV4 having more
      universal, widespread distribution along different vascular segments. We suggest
      that TRPV1/4 channels are potent therapeutic targets for site-specific
      vasodilation in the kidney.

PMID- 25069879
TI  - Plasma-based ambient desorption/ionization mass spectrometry: state-of-the-art in
      qualitative and quantitative analysis.
AB  - Ambient desorption/ionization mass spectrometry (ADI-MS) aims to enable direct
      analysis of gaseous, liquid, and/or solid samples under ambient conditions. In
      ADI-MS, different types of desorption/ionization sources are classified according
      to their basic method of operation, namely spray-based, laser-based, or plasma
      based. This review discusses many of the plasma-based techniques coupled to mass
      spectrometry in terms of their current performance in fast qualitative screening
      and quantitative analysis. Critical aspects, for example sample preparation and
      introduction, quantification, and matrix effects, are addressed. Furthermore, the
      applicability of plasma-based sources to portable mass spectrometers and their
      capabilities in imaging experiments are summarized. The applications discussed
      are of two types. In one, direct screening is performed without any or with
      minimal sample pretreatment. Samples with low matrix content are qualitatively
      analyzed without interferences. The other, more challenging applications, namely
      samples with high matrix content and most quantitative analysis, typically
      require sample preparation ranging from simple dilution to extensive multi-step
      procedures. 

PMID- 25069878
TI  - Self-induced vomiting and dental erosion--a clinical study.
AB  - BACKGROUND: In individuals suffering from eating disorders (ED) characterized by
      vomiting (e.g. bulimia nervosa), the gastric juice regularly reaches the oral
      cavity, causing a possible risk of dental erosion. This study aimed to assess the
      occurrence, distribution and severity of dental erosions in a group of Norwegian
      patients experiencing self-induced vomiting (SIV). METHODS: The individuals
      included in the study were all undergoing treatment at clinics for eating
      disorders and were referred to a university dental clinic for examinations. One
      calibrated clinician registered erosions using the Visual Erosion Dental
      Examination (VEDE) system. RESULTS: Of 72 referred patients, 66 (63 females and
      three males, mean age 27.7 years) were or had been experiencing SIV (mean
      duration 10.6 years; range: 3 - 32 years), and were therefore included in the
      study. Dental erosions were found in 46 individuals (69.7%), 19 had enamel
      lesions only, while 27 had both enamel and dentine lesions. Ten or more teeth
      were affected in 26.1% of those with erosions, and 9% had >=10 teeth with dentine
      lesions. Of the erosions, 41.6% were found on palatal/lingual surfaces, 36.6% on
      occlusal surfaces and 21.8% on buccal surfaces. Dentine lesions were most often
      found on lower first molars, while upper central incisors showed enamel lesions
      most frequently. The majority of the erosive lesions (48.6%) were found in those
      with the longest illness period, and 71.7% of the lesions extending into dentine
      were also found in this group. However, despite suffering from SIV for up to 32
      years, 30.3% of the individuals showed no lesions. CONCLUSIONS: Dental erosion
      commonly affects individuals with ED experiencing SIV, and is more often found on
      the palatal/lingual surfaces than on the buccal in these individuals, confirming
      a common clinical assumption.

PMID- 25069880
TI  - Advanced food analysis.

PMID- 25069881
TI  - Determination of urinary nucleosides via borate complexation capillary
      electrophoresis combined with dynamic pH junction-sweeping-large volume sample
      stacking as three sequential steps for their on-line enrichment.
AB  - The combination of dynamic pH junction, sweeping (using borate complexation), and
      large volume sample stacking (LVSS) is investigated as three consecutive steps
      for on-line focusing in the sensitive quantitation of urinary nucleosides by CE
      UVD. A low conductivity aqueous sample matrix free from borate and a high
      conductivity BGE (containing borate, pH 9.25) are needed to fulfill the required
      conditions for dynamic pH junction, LVSS, and sweeping. Parameters affecting the
      separation and the enrichment efficiency are studied such as buffer
      concentration, separation voltage, capillary temperature, sample composition, and
      sample injection volume. Prerequisite for the developed strategy is the
      extraction of the nucleosides from urine using a phenylboronate affinity gel,
      which is described to be a unique means for the selective enrichment of cis-diol
      metabolites under alkaline conditions. The impact of ionic constituents remaining
      in the eluate after extraction on focusing efficiency and resolution is
      investigated. The developed method is applied to the analysis of blank and spiked
      urine samples. Fundamental aspects underlying the proposed enrichment procedure
      are discussed. A detection limit as low as 10 ng mL(-1) is achieved. To the best
      of our knowledge, this LOD represents the lowest LOD reported so far for the
      analysis of nucleosides using CE with UV detection and provides a comparable
      sensitivity to CE/MS. Because of the high sensitivity, the proposed method shows
      a great potential for the analysis of nucleosides in human urine and other types
      of biological fluids. 

PMID- 25069882
TI  - Hexafluoroisopropanol-induced coacervation in aqueous mixed systems of cationic
      and anionic surfactants for the extraction of sulfonamides in water samples.
AB  - Hexafluoroisopropanol (HFIP)-induced coacervation in aqueous mixed systems of
      catanionic surfactants of dodecyltrimethylammonium bromide (DTAB) and sodium
      dodecyl sulfate (SDS) was described in detail, and its application in the
      extraction of strongly polar sulfonamides (SAs) was investigated. With 10 % (v/v)
      HFIP inclusion, coacervation formation and two-phase separation occur in a wide
      range of SDS/DTAB mole ratios (88:12~0:100 mol/mol) and total surfactant
      concentrations (10~200 mmol/L). The interactions between HFIP and DTAB play an
      important role in coacervation formation. The HFIP-induced SDS-DTAB coacervation
      extraction proves to be an efficient method for the extraction and
      preconcentration of SAs. Both hydrophobic interaction and polar interactions
      (hydrogen-bond, electrostatic, and pi-cation) contribute to the distribution of
      SAs into coacervate phase. The proposed HFIP-induced SDS-DTAB coacervation
      extraction combined with HPLC-UV was employed for the extraction and quantitative
      determination of SAs in environmental water samples. Limits of detection were
      1.4~2.5 ng mL(-1). Excellent linearity with correlation coefficients from 0.9990
      to 0.9995 was obtained in the concentration of 0.01~10 MUg mL(-1). Relative
      recoveries were in the range of 93.4~105.9 % for analysis of the lake,
      underground, and tap water samples spiked with SAs at 0.01, 1.0, and 10 MUg/mL,
      respectively. Relative standard deviations were 0.7~3.2 % for intraday precision
      and 1.3~4.6 % for interday precision (n = 3). Concentration factors were 17~49
      for three water samples spiked with 0.01 MUg/mL SAs. The results demonstrate that
      the proposed extraction method is feasible for the preconcentration and
      determination of trace SAs in real water samples. 

PMID- 25069883
TI  - Simultaneous determination of reduced and oxidized glutathione in tissues by a
      novel liquid chromatography-mass spectrometry method: application in an
      inhalation study of Cd nanoparticles.
AB  - The paper presents the development of an advanced extraction and fast analytical
      LC MS/MS method for simultaneous analyses of reduced and oxidized glutathione
      (GSH and GSSG, respectively) in different animal tissues. The simultaneous
      determination of GSH and GSSG is crucial because the amount and ratio of both GSH
      and GSSG may be altered in response to oxidative stress, an important mechanism
      of toxicity. The method uses the derivatization of free thiol groups in GSH. Its
      performance was demonstrated for less explored tissues (lung, brain, and liver)
      in mouse. The combined extraction and analytical method has very low variability
      and good reproducibility, maximum coefficients of variance for within-run and
      between-run analyses under 8 %, and low limits of quantification; for GSH and
      GSSG, these were 0.2 nM (0.06 ng/mL) and 10 nM (6 ng/mL), respectively. The
      performance of the method was further demonstrated in a model experiment
      addressing changes in GSH and GSSG concentrations in lung of mice exposed to CdO
      nanoparticles during acute 72 h and chronic 13-week exposures. Inhalation
      exposure led to increased GSH concentrations in lung. GSSG levels were in general
      not affected; nonsignificant suppression occurred only after the longer 13-week
      period of exposure. The developed method for the sensitive detection of both GSH
      and GSSG in very low tissue mass enables these parameters to be studied in cases
      where only a little sample is available, i.e. in small organisms or in small
      amounts of tissue. 

PMID- 25069884
TI  - Aquagenic palmoplantar keratoderma: a sign of cystic fibrosis early in life.

PMID- 25069885
TI  - Electrocardiographic characteristics of the right ventricle following hemodynamic
      improvement after percutaneous pulmonary valve implantation, one year follow-up.
AB  - Percutaneous pulmonary valve implantation (PPVI) is an alternative to open-heart
      surgery in patients with congenital heart defect. The purpose of the study is to
      evaluate right ventricle (RV) electrocardiographic characteristics in relation
      with hemodynamic changes after PPVI. In 30 patients (16 males, aged 24+/-7years),
      ECG RV characteristics changes (R amplitude in V1 and aVR, Sokolow-Lyon index
      (SL) for RV hypertrophy, QRS duration) from before and 1year after PPVI were
      correlated with changes in RV end-diastolic volume (RVEDV), RV end-systolic
      volume (RVESV), RV ejection fraction (RVEF), RV mass in cardiac magnetic
      resonance (cMRI) and within pulmonary gradient in echocardiography. Significant
      correlations were observed: decrease R amplitude in aVR correlated to decrease
      RVESV and RV mass; decrease RVESV and pulmonary gradient to reduction in SL-V5;
      increase RVEF to reduction R aVR and SL-V5. Improvement of hemodynamic parameters
      in cMRI and echocardiography is parallel to that of electrocardiographic criteria
      of RV hypertrophy. 

PMID- 25069886
TI  - Variability in the measurement of the methylation status of lung cancer-related
      genes in bronchial secretions.
AB  - Assessment of the methylation status of genes related to the development of lung
      cancer (LC) in bronchial secretions has been proposed as a biomarker for early
      detection. Several techniques are available to detect gene methylation, and the
      method chosen may have an effect on the results. A cross-sectional study was
      conducted in which the methylation status of DAPK, CDKN2A (p16) and RASSF1A genes
      in sputum and bronchial washing (BW) from subjects at risk for LC was analyzed.
      The methylation results of both samples were compared, considering BW as the
      reference. Results obtained by methylation-sensitive PCR (MSP) were validated by
      methylation-sensitive high-resolution melting (MS-HRM). The methylation results
      obtained in sputum and BW samples did not show statistically significant
      differences for any of the three genes analyzed in 65 subjects (McNemar
      test>0.05). Concordant results between sputum and BW were found in 40 patients
      for DAPK (61%), in 52 patients for p16 (80%) and in 63 patients for RASSF1 (97%).
      More methylated samples were found in BW, however, and sputum sensitivities and
      specificities for the identification of methylation status were 44 and 72% for
      DAPK gene, 21 and 94% for p16 and 100 and 98% for RASSF1A, respectively. When MSP
      results were validated by MS-HRM, DAPK and p16 gene samples methylated by MSP
      appeared to be unmethylated by MS-HRM. One sample showing methylation of RASSF1A
      gene also showed methylation when tested following MS-HRM procedure. Sputum and
      BW samples may be considered equally valid for the identification of methylated
      genes in bronchial secretions. The low sensitivity of sputum for the assessment
      of the methylation status of DAPK and p16 genes, however, suggests that the
      analysis of two or more sputum samples, or of a BW obtained semi-invasively,
      would be needed to attain higher reliability, together with the use of
      confirmatory techniques for positive results.

PMID- 25069887
TI  - Apple polyphenol extracts protect against aspirin-induced gastric mucosal damage
      in rats.
AB  - The protective role of two apple polyphenol extracts, Douglas-FB (FB) and Douglas
      EF (EF), on gastric mucosal damage following aspirin ingestion was investigated
      in healthy rats. Polyphenol content of the apple extracts varied, with the EF
      extract having 20% w/w polyphenols and a high proportion of flavanols as
      epicatechin and procyanidin, whereas the FB extract comprised 12% w/w
      polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague
      Dawley rats were allocated to control, FB and EF groups and fed the experimental
      diet during the 10-day trial. Control treatment rats received 1 mL of deionised
      water, whereas apple polyphenol treatment group rats, FB and EF received a
      concentration of 10(-2)  m polyphenols in 1 mL deionised water daily via oral
      gavage. At the end of 10-day feeding period, rats were fasted overnight, and the
      following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after
      aspirin administration, the animals were euthanised, and samples taken for
      analysis. Both apple polyphenol extracts significantly reduced the ulcer area,
      ulcer lesion index and gastric injury score. The glutathione in gastric mucosa
      was increased significantly in rats given FB apple extract. Despite their
      different polyphenol compositions, FB and EF apple extracts assisted in
      protecting the gastric mucosa following acute aspirin administration in rats.

PMID- 25069888
TI  - Immunological profile of periapical endodontic infections from HIV- and HIV+
      patients.
AB  - AIM: To evaluate CD4(+) CD28(+) and CD8(+) T-cell genes and the gene expression
      of IFN-gamma, TNF-alpha, IL-1-beta, IL-17A, IL-10, CCL-2/MCP-1, CCL-4, CCL-5
      (RANTES), CXCR4, CCR5 and RANKL from cells in the periapical interstitial fluid
      from root canal infections in healthy patients (HIV-) and HIV-positive
      individuals (HIV+). METHODOLOGY: Subjects included 20 HIV- and 23 HIV+ patients
      referred to the School of Dentistry at the Universidade Federal de Minas Gerais
      (Belo Horizonte, MG, Brazil). Almost all HIV+ patients were undergoing highly
      active antiretroviral therapy (HAART). Clinical samples were taken from teeth
      with pulp necrosis, and no patients had acute periapical symptoms at the time of
      the appointments. After cleaning and drying, 3 paper points were introduced into
      the root canal, passing passively through the root apex (2 mm) into the
      periapical tissues for 1 min. The samples were collected immediately after root
      canal cleaning and 7 days later (restrained root canal bacterial load) to
      characterize those gene expressions using real-time PCR. RESULTS: Significantly
      higher levels of CD4(+) CD28(+) and CD8(+) T cells in teeth with restrained
      bacterial loads (second collection) compared with the first collection were
      observed in both HIV- and HIV+ samples. In HIV- patients, an increase in IL-10
      and CXCR4 expression was demonstrated as well as a decrease in pro-inflammatory
      cytokines such as RANKL, IFN-gamma, IL1-beta and CCL5. However, in HIV+ patients
      an increase in cytokines IFN-gamma, IL-1-beta, TNF-alpha and IL-17A, and
      chemokines CCL-2, CXCR4 and CCR5 were observed. The chemokine CCL-5 was not
      detected in HIV+ individuals. CONCLUSIONS: These findings suggest that after
      reducing the root canal bacterial load in HIV- individuals an anti-inflammatory
      response is generated whilst in HIV+ patients a pro-inflammatory response is
      sustained in the periapical area.

PMID- 25069890
TI  - Enhancement and inhibition effects of water matrices during the sonochemical
      degradation of the antibiotic dicloxacillin.
AB  - The sonochemical degradation of dicloxacillin (DXC) was studied in both synthetic
      and natural waters. Degradation routes and the effect of experimental conditions
      such as pH, initial DXC concentration and ultrasonic power were evaluated.
      Experiments were carried out with a fixed frequency (600kHz). The best
      performances were achieved using acidic media (pH=3) and high power (60W). The
      degradation process showed pseudo-first order kinetics as described by the Okitsu
      model. To evaluate water matrix effects, substrate degradation, in the presence
      of Fe(2+) and organic compounds such as glucose and 2-propanol, was studied. A
      significant improvement was achieved with Fe(2+) (1.0mM). Inhibition of the
      degradation process was observed at a relatively high concentration of 2-propanol
      (4.9mM), while glucose did not show any effect. Natural water showed an
      interesting effect: for a low concentration of DXC (6.4MUM), an improvement in
      the degradation process was observed, while at a higher concentration of DXC
      (0.43mM), degradation was inhibited. Additionally, the extent of degradation of
      the process was evaluated through the analysis of chemical oxygen demand (COD),
      antimicrobial activity, total organic carbon (TOC) and biochemical oxygen demand
      (BOD5). A 30% removal of COD was achieved after the treatment and no change in
      the TOC was observed. Antimicrobial activity was eliminated after 360min of
      ultrasonic treatment. After 480min of treatment, a biodegradable solution was
      obtained. 

PMID- 25069889
TI  - Ultrasound assisted enzyme catalyzed synthesis of glycerol carbonate from
      glycerol and dimethyl carbonate.
AB  - The present work illustrates the transesterification of glycerol to glycerol
      carbonate (GlyC) from dimethyl carbonate (DMC) using commercial immobilized
      lipase (Novozym 435) under ultrasonic irradiation. The experiments were performed
      in a batch reactor placed in an ultrasonic water bath using a sequence of
      experimental protocol to evaluate the effects of temperature, molar ratios of
      substrates, enzyme loading, duty cycle and ultrasound power on the conversion of
      glycerol to GlyC. It has been found that ultrasound-assisted lipase-catalyzed
      transesterification of glycerol would be a potential alternative to conventional
      alkali-catalyzed method, as high conversion (99.75%) was obtained at mild
      operating conditions: molar ratio of DMC to glycerol 3:1, catalyst amount of 13%
      (w/w), lower power input (100W), duty cycle 50% and temperature (60 degrees C) in
      a relatively short reaction time (4h) using Novozym 435 as catalyst. Ultrasound
      reduces the reaction time up to 4h as compared to conventional stirring method
      (14h) catalyzed by Novozym 435. The repeated use of the catalyst under the
      optimum experimental condition resulted in decay in both enzyme activity and
      product conversion. 

PMID- 25069891
TI  - Manno-oligosaccharide-binding ability of mouse RegIV/GST-fusion protein evaluated
      by complex formation with the carbohydrate-containing polyamidoamine dendrimer.
AB  - The carbohydrate-binding properties of the C-type lectin-like mouse RegIV and
      glutathione S-transferase-fusion protein (GST-mRegIV) were examined using
      carbohydrate-containing polyamidoamine dendrimers (PD). GST-mRegIV showed
      affinity for mannan- and manno-oligosaccharide containing PD. Binding was
      inhibited by manno-oligosaccharides but not by mannose or other tested
      carbohydrates, suggesting that the binding site may have an extended structure in
      contrast with typical C-type lectins.

PMID- 25069892
TI  - Noninvasive fetal QRS detection using an echo state network and dynamic
      programming.
AB  - We address a classical fetal QRS detection problem from abdominal ECG recordings
      with a data-driven statistical machine learning approach. Our goal is to have a
      powerful, yet conceptually clean, solution. There are two novel key components at
      the heart of our approach: an echo state recurrent neural network that is trained
      to indicate fetal QRS complexes, and several increasingly sophisticated versions
      of statistics-based dynamic programming algorithms, which are derived from and
      rooted in probability theory. We also employ a standard technique for
      preprocessing and removing maternal ECG complexes from the signals, but do not
      take this as the main focus of this work. The proposed approach is quite generic
      and can be extended to other types of signals and annotations. Open-source code
      is provided. 

PMID- 25069893
TI  - Systematic literature review of adverse reproductive outcomes associated with
      physiotherapists' occupational exposures to non-ionising radiation.
AB  - OBJECTIVES: To review empirical research on adverse health and pregnancy outcomes
      associated with physiotherapists' occupational exposure to radiofrequency
      electromagnetic fields (RF EMFs) from shortwave (SWD) and microwave (MWD)
      diathermy devices. METHODS: A systematic review of peer reviewed literature
      published from 1990 to 2010 in the English language searched in eight online
      bibliographic databases: CINAHL, EBSCOhost, ISI Web of Knowledge, Medline, OSH
      UPDATE, PubMed Central, ScienceDirect, and Scopus. RESULTS: Findings suggest that
      physiotherapists' occupational exposure to SWD was statistically significantly
      associated with delayed time to pregnancy (>6 months), still birth, altered
      gender ratio (low ratio of boys to girls), congenital malformations and low birth
      weight (<2,500 g) among physiotherapists' offspring. Physiotherapists' exposure
      to MWD was also found to be statistically significantly associated with
      spontaneous abortion. However, causal mechanisms for these statistical
      associations are unknown. The present systematic review has found these adverse
      reproductive outcomes and health effects associations with RF EMFs from
      therapeutic diathermy devices to be inconsistent. CONCLUSIONS: A number of
      studies did not find statistically significant results to replicate associations
      with such adverse outcomes, and therefore further research, preferably
      prospective studies of cohorts of physiotherapists, is warranted.

PMID- 25069894
TI  - Re-characterization of some factors influencing aerosol sampling in the
      workplace: results from field studies.
AB  - OBJECTIVE: Workplace aerosol sampling is challenged by its influencing factors
      and methodological limitations. Some factors, including blank setting,
      electrostatic effect, sample mass gain, and limit of detection (LOD), were
      studied to characterize them further and thereby to improve the sampling method.
      METHODS: Through a field sampling in two shipyards and by an analysis of a large
      amount of dust data from different industries, the influencing factors were
      comparatively studied with emphasis on their effect on the final result. RESULTS:
      After calibration with field blanks, the concentrations of most sample types in
      the shipyards decreased significantly, varying by as much as -24.3% of the final
      measurements. After laboratory blank calibration, dust concentrations increased
      or decreased without a definite change trend. With a variation of -1.8%, only the
      measurements of Chinese "total dust" sampled with polypropylene filters were
      significantly influenced by the electrostatic effect. The LOD coincidence rate
      was only 17.3% for American respirable dust in different industries and 12.2% for
      respirable particles collected by normal flow rate samplers (FSP2) in the
      shipyards. The latter increased to 73.9% when high flow samplers (FSP10) were
      used. CONCLUSIONS: It was suggested that field blank calibration was the
      predominant influencing factor in comparison with electrostatic effect and
      laboratory blank adjustment. The LOD coincidence rate was too low for reliable
      sampling, and this might be improved by use of high flow samplers.

PMID- 25069895
TI  - Solvent use in private research laboratories in Japan: comparison with the use in
      public research laboratories and on production floors in industries.
AB  - BACKGROUND AND OBJECTIVES: Solvents used in production facility-affiliated
      private laboratories have been seldomly reported. This study was initiated to
      specify solvent use characteristics in private laboratories in comparison with
      the use in public research laboratories and on production floors. Elucidation of
      the applicability of conclusions from a public laboratory survey to private
      institutions is not only of scientific interest but also of practical importance.
      MATERIALS: A survey on use of 47 legally stipulated organic solvents was
      conducted. The results were compiled for April 2011 to March 2013. Through
      sorting, data were available for 479 unit workplaces in private laboratories.
      Similar sorting for April 2012 to March 2013 was conducted for public research
      laboratories (e.g., national universities) and production floors (in private
      enterprises) to obtain 621 and 937 cases, respectively. Sampling of workroom air
      followed by capillary gas-chromatographic analyses for solvents was conducted in
      accordance with regulatory requirements. RESULTS: More than one solvent was
      usually detected in the air of private laboratories. With regard to solvent
      types, acetone, methyl alcohol, chloroform and hexane were prevalently used in
      private laboratories, and this was similar to the case of public laboratories.
      Prevalent use of ethyl acetate was unique to private laboratories. Toluene use
      was less common both in private and public laboratories. The prevalence of
      administrative control class 1 (i.e., an adequately controlled environment) was
      higher in laboratories (both private and public) than production floors.
      CONCLUSIONS: Solvent use patterns are similar in private and public laboratories,
      except that the use of mixtures of solvents is substantially more popular in
      private laboratories than in public laboratories.

PMID- 25069896
TI  - Chemical exposure levels in printing workers with cholangiocarcinoma.
AB  - OBJECTIVE: This study aimed to identify chemicals used by printing workers with
      cholangiocarcinoma, as well as the levels of exposure to the chemicals. METHODS:
      Information necessary to identify chemicals used by printing workers with
      cholangiocarcinoma and to estimate chemical exposure concentrations was obtained
      from the Ministry of Health, Labour and Welfare, Japan. Working environment
      concentrations of the chemicals in the printing rooms were estimated using a well
      mixed model, and exposure concentrations during the ink removal operation were
      estimated using a near-field and far-field model. Shift time- weighted averages
      (TWA) of exposure concentrations were also calculated. RESULTS: Two workers from
      each of three small printing plants examined suffered from cholangiocarcinoma,
      and all six of these workers had been exposed to 1,2-dichloropropane (1,2-DCP)
      for 10-16 years. The estimated working environment concentrations of 1,2-DCP in
      the printing rooms were 17-180 ppm and estimated exposure concentrations during
      the ink removal operation were 150-620 ppm. Shift TWA values were estimated to be
      62-240 ppm. Four of the six workers had also been exposed to dichloromethane
      (DCM) at estimated working environment concentrations of 0-98 ppm and estimated
      exposure concentrations during the ink removal operation of 0-560 ppm. Shift TWA
      values were estimated to be 0-180 ppm. Other chlorinated organic solvents (1,1,1
      trichloroethane, 1,1-dichloro-1-fluoroethane) and petroleum solvents (gasoline,
      naphtha, mineral spirit, mineral oil, kerosene) were also used in the ink removal
      operation. CONCLUSIONS: All six printing workers with cholangiocarcinoma were
      exposed to very high levels of 1,2-DCP for a long term.

PMID- 25069897
TI  - A method for routine analysis of urinary 4,4'-methylenebis (2-chloroaniline) by
      gas chromatography-electron capture detection.
AB  - OBJECTIVES: The purpose of this study was to develop a simple and cost-effective
      method for the determination of urinary 4,4'-methylenebis (2-chloroaniline)
      (MBOCA) by gas chromatography-electron capture detection (GC-ECD) for biological
      monitoring of occupational exposure to MBOCA. METHODS: MBOCA was prepared by
      liquid-liquid extraction after alkaline hydrolysis, derivatized with N-methyl-bis
      (trifluoroacetamide) and then analyzed using GC-ECD. The proposed method was
      validated in accordance with the US Food and Drug Administration guidance.
      RESULTS: The calibration curve showed linearity in the range 1-100 ug/l, with a
      correlation coefficient of >0.999. The limits of detection and quantification
      were 0.3 ug/l and 1 ug/l, respectively. The recovery was 94-99%. Intraday
      accuracy, expressed as the deviation from the nominal value, was 90.5-100.3%, and
      intraday precision, expressed as the relative standard deviation, was 0.3-2.4%.
      Interday accuracy and precision were 87.8-100.2% and 0.3-4.1%, respectively.
      CONCLUSIONS: The proposed method is a simple and cost-effective method suitable
      for routine analyses and could be useful for biological monitoring of
      occupational exposure to MBOCA.

PMID- 25069898
TI  - How "standardized" is standardized? A validation of postcranial landmark
      locations.
AB  - Since the mid-1990s, osteometrics have been a major aspect in forensic
      anthropology. However, recent evidence has shown that practitioners have been
      using differing points to establish certain measurements; namely those involving
      the clavicle, scapula, ulna, femur, and tibia. Engaging 61 practitioners, this
      study examined and confirmed how extensive this discord is. The highest
      consistency rate among practitioners was the scapular breadth (62.3%), followed
      by the femoral anteroposterior subtrochanteric diameter (55%). All other levels
      fell below these, particularly the physiological length of the ulna which was the
      most inconsistently measured bone. Furthermore, these low consistency rates
      yielded percent mean differences between two and 20% of the measurement length,
      with ranges averaging 14 mm. In light of these results, it is recommended that
      the field take steps to improve the standardization of such problematic
      measurements, including reexamining all measurements currently listed in
      osteometric texts, reassessing the utility of each, and reissuing a comprehensive
      guide. 

PMID- 25069899
TI  - Enzymatic glycosylation of the topical antibiotic mupirocin.
AB  - Mupirocin is a commercially available antibiotic that acts on bacterial isoleucyl
      tRNA synthetase, thereby inhibiting protein synthesis and preventing bacterial
      infection. An in vitro glycosylation approach was applied to synthesize glycoside
      derivatives of mupirocin using different NDP-sugars and glycosyltransferase from
      Bacillus licheniformis. Ultra pressure liquid chromatography-photo diode array
      analyses of the reaction mixtures revealed the generation of product peak(s). The
      results were further supported by high-resolution quadruple time of flight
      electrospray ionization mass spectrometry analyses. The product purified from the
      reaction mixture with UDP-D-glucose was subjected to NMR analysis, and the
      structure was determined to be mupirocin 6-O-beta-D-glucoside. Other glycoside
      analogs of mupirocin were determined based on high-resolution mass analyses.
      Antibacterial activity assays against Staphylococcus aureus demonstrated complete
      loss of antibacterial activity after glucosylation of mupirocin at the 6-hydroxyl
      position.

PMID- 25069900
TI  - Work-family conflict as a mediator in the association between work stress and
      depressive symptoms: cross-sectional evidence from the German lidA-cohort study.
AB  - OBJECTIVE: The demographic change leads to a shrinking German work force.
      Depressive symptoms cause many days absent at work, loss of productivity and
      early retirement. Therefore, pathways for prevention of depressive symptoms are
      important for the maintenance of global competitiveness. We investigated the role
      of work-family conflict (WFC) in the well-known association between work stress
      and depressive symptoms. METHODS: A total of 6,339 employees subject to social
      insurance, born in 1959 or 1965 and randomly drawn from 222 sample points in
      Germany participated in the first wave of the leben in der Arbeit-study. In the
      analysis, 5,906 study subjects working in full-time or part-time positions were
      included. Work stress was measured by effort-reward imbalance ratio, depressive
      symptoms by the applied Becks depression inventory (BDI-V) and WFC by items of
      the Copenhagen Psychosocial Questionnaire (COPSOQ)-scale. Multiple linear
      regression analysis adjusted for age, education, negative affectivity (PANAS),
      overcommitment and number of children was performed. Mediation was defined
      according to the criteria of Baron and Kenny. RESULTS: Work stress was
      significantly associated with depressive symptoms (BDI-V) in all full-time
      [beta1female = 6.61 (95 % CI 3.95-9.27); beta1male = 8.02 (95 % CI 5.94-10.09)]
      and female part-time employees [beta2female = 4.87 (95 % CI 2.16-7.59)]. When
      controlling for WFC effect, estimates became smaller in men and were even halved
      in women. WFC was also significantly associated with work stress and depressive
      symptoms: All criteria for partial mediation between work stress and
      depressiveness were fulfilled. CONCLUSIONS: Prevention of WFC may help to reduce
      days absent at work and early retirement due to work stress-related depressive
      symptoms in middle-aged women and men.

PMID- 25069901
TI  - A hybrid solid-fluorous phase radioiodination and purification platform.
AB  - A new class of fluorous materials was developed to create a hybrid solid-solution
      phase strategy for the expedient preparation and HPLC-free purification of (125)
      I-labeled compounds. The system is referred to as a hybrid platform in that it
      combines solution phase labeling and fluorous solid-phase purification in one
      step as opposed to two separate individual processes. Treatment of fluorous
      arylstannanes coated on fluorous silica with [(125) I]NaI and the appropriate
      oxidant made it possible to produce and selectively isolate the nonfluorous
      radiolabeled products in high purity (>98%) free from excess starting material
      and unreacted radioiodine. Examples included simple aryl and heterocyclic (click)
      derivatives, known radiopharmaceuticals including meta-iodobenzylguanidine (MIBG)
      and iododeoxyuridine (IUdR), and a new agent with high affinity for prostate
      specific membrane antigen. The coated fluorous silica kits are simple to prepare,
      and reactions can be performed at room temperature using different oxidants
      generating products in minutes in biocompatible solutions. 

PMID- 25069902
TI  - Evaluation of the performance of paraplegic subjects during walking with a new
      design of reciprocal gait orthosis.
AB  - BACKGROUND: Spinal cord injury (SCI) influences a person's ability to stand and
      walk. Various orthoses have been developed to solve these standing and walking
      problems, however, patients still experience high energy consumption during
      walking and high forces on the upper limbs. A new reciprocal gait orthosis (RGO)
      was designed to address these problems. The aim of this study was to evaluate the
      performance of the new orthosis design with paraplegic subjects. METHOD: Three
      paraplegic subjects with the lesion at level T12 and three able-bodied subjects
      were included in this study. Hip and pelvis range of motion and vertical ground
      reaction force were evaluated using the Qualysis motion analyzer system and a
      Kistler force plate. Energy consumption was measured with the Polar heart rate
      monitoring system. The differences between SCI individuals when walking with a
      Knee Ankle Foot Orthosis (KAFO) and the new RGO, and the differences between able
      bodied and paraplegic subjects were evaluated by the use of paired sample and two
      sample t test, respectively. RESULT: The results showed that energy consumption
      and gait analysis outcomes with new RGO orthosis were better than the KAFO.
      However, there was a large difference between paraplegic and able-bodied subjects
      while walking with the new orthosis. CONCLUSION: The new RGO design performed
      better than a KAFO in terms of energy consumption, walking style and vertical
      ground reaction force. Therefore, it appears that RGO may be a useful orthosis
      for patients with paraplegia. Implications for Rehabilitation Walking and
      standing of the subjects with spinal cord injury (SCI) improve their
      physiological and physiological health. This study introduces a new type of
      orthosis design in order to improve the abilities of SCI subjects during walking
      and standing. It seems that the new design works better than available orthoses
      (KAFO).

PMID- 25069903
TI  - Factors influencing cardiometabolic monitoring practices in an adult community
      mental health service.
AB  - People with serious mental illness are reported to live up to 25 years less than
      the general population. Cardiovascular disease and diabetes risk factors, as well
      as mental health, treatment, lifestyle, service provision, and socioeconomic
      factors, all contribute to this health inequity. Cardiometabolic monitoring (CMM)
      is one strategy used to attend to some cardiometabolic risk factors. The present
      study aimed to explore factors that influence decisions to undertake CMM in an
      Australian adult community mental health service. A CMM audit tool was designed
      to capture demographic, clinical, and care-provision factors. A 6-month
      retrospective file audit from the total population of consumers of an adult
      community mental health service was undertaken, where no existing CMM guidelines
      or practices were in place. The study findings confirmed a higher prevalence of
      cardiometabolic disorders in the study population compared to the general
      population. Complete CMM occurred in 24% of the study population (n = 94). No
      consumer demographic, socioeconomic, or clinical characteristics, or care
      provision factors, were found to be predictors of complete CMM. The random manner
      in which CMM was observed to occur in the study highlights the need for
      standardized CMM guidelines and capacity-building strategies to improve current
      CMM practices. 

PMID- 25069904
TI  - Global climate change and contaminants, a call to arms not yet heard?

PMID- 25069905
TI  - Diagnostic imaging in paraneoplastic autoimmune multiorgan syndrome:
      retrospective single site study and literature review of 225 patients.
AB  - BACKGROUND: The utility of diagnostic imaging in paraneoplastic autoimmune
      multiorgan syndrome (PAMS) is unknown. METHODS: We examined the role of
      diagnostic imaging in patients with PAMS evaluated at our tertiary referral
      center (at Mayo Clinic, Rochester, MN, USA) and in the English literature between
      January 1, 1996, and August 31, 2012. RESULTS: We included 17 patients from our
      institution and 208 patients from the literature review. Of these 225 patients,
      113 (50.2%) were not known to have a malignancy diagnosis at the time of PAMS
      diagnosis. Of the 123 patients from our institution and from the literature
      reported to undergo imaging studies, conventional computed tomography (CT) was
      the predominant imaging modality (n = 110; 89.4%); 18F-fluorodeoxyglucose (18F
      FDG) positron emission tomography (PET)/CT was also used, albeit infrequently (n
      = 12; 9.8%). When CT was included in imaging to identify or confirm the presence
      of a malignancy, imaging was successful in all patients who ultimately were
      diagnosed with an associated malignancy. At our institution, a relatively high
      percentage (n = 7; 41%) of patients had 18F-FDG PET/CT, which not only identified
      all tumors found on CT but also facilitated staging of lymphoma and guided biopsy
      procedures. CONCLUSION: Diagnostic imaging is frequently utilized in PAMS with
      unknown malignancy. Both conventional CT and 18F-FDG PET/CT are likely to detect
      the typical underlying neoplasms. Relative to conventional CT, 18F-FDG PET/CT may
      provide additional useful information regarding prognosis for the likely
      underlying malignancies, although there is a paucity of reports describing the
      use of this modality for this purpose.

PMID- 25069906
TI  - Levels of evidence for the outcome of regenerative endodontic therapy.
AB  - INTRODUCTION: The aim of this systematic review was to assign levels of evidence
      (LOEs) to existing clinical articles related to the outcome of regenerative
      endodontic therapy and to evaluate the clinical and radiographic outcomes of this
      treatment modality. METHODS: Electronic search was executed in PubMed, Scopus,
      and Cochrane databases by using appropriate Medical Subject Headings terms
      covering the period from January 1993 to December 2013. Additional publications
      from hand-searching and reference section of each relevant article enriched the
      article list. The LOE of each article was assessed according to guidelines
      provided by the Oxford Centre of Evidence-Based Medicine. Quality assessment of
      the observational studies was executed by using the Newcastle-Ottawa scale.
      RESULTS: Fifty-one relevant publications were included in this review. There were
      2 high-level cohort studies (LOE 2), 8 case series (LOE 4), and 41 case reports
      (LOE 5). The vast majority of the treated teeth in those publications showed
      resolution of clinical signs, symptoms, and periapical radiolucencies at follow
      up period. Furthermore, the majority of treated teeth presented further increase
      in root length and root wall thickness and apical closure at the follow-up
      period. However, because of lack of sufficient high-level evidence it was not
      possible to answer totally the review question and determine definitely the
      outcome of regenerative endodontic therapy. CONCLUSIONS: The lack of adequate
      high-level studies that could possibly strengthen the satisfactory current data
      and allow practicing more evidence-based dentistry constitutes a significant
      knowledge gap in the endodontic literature. However, the current best available
      evidence undeniably allows clinicians to provide this treatment modality safely
      to patients.

PMID- 25069907
TI  - Oxygen saturation in the dental pulp of permanent teeth: a critical review.
AB  - INTRODUCTION: Pulse oximetry is a noninvasive method for assessing vascular
      health based on oxygen saturation level. The method has recently also been used
      to assess dental pulp vitality, but a median oxygen saturation level suggestive
      of normal pulp physiology has not been determined. The objective of this study
      was to make a critical analysis of the published research to establish the median
      oxygen saturation for the diagnosis of normal dental pulps in maxillary anterior
      permanent teeth using pulse oximetry. METHODS: Studies reporting on the use of
      pulse oximeters to determine oxygen saturation in dental pulps were retrieved
      using the MEDLINE, Scientific Electronic Library Online, and Cochrane Central
      Register of Controlled Trials databases plus a manual search of relevant
      references cited by selected articles. Different combinations of the terms
      "oximetry," "oximeter," "pulp," "dental," and "dentistry" were used in the
      search. Statistical analysis was performed for each group of teeth (central
      incisors, lateral incisors, and canines) using R statistical software (US EPA ORD
      NHEERL, Corvallis, OR) and a random effects model (P < .0001) with an I(2) of
      99%. RESULTS: Of the 295 articles found, only 6 met the inclusion criteria (472
      teeth). Of these, the number of articles included in each analysis (according to
      tooth group) was as follows: all 6 studies (288 teeth) for central incisors at a
      median oxygen saturation of 87.73%, 3 studies (90 teeth) for lateral incisors at
      a median oxygen saturation of 87.24%, and 4 studies (94 teeth) for canines at a
      median oxygen saturation of 87.26%. CONCLUSIONS: The median oxygen saturation in
      normal dental pulps of permanent central incisors, lateral incisors, and canines
      was higher than 87%.

PMID- 25069908
TI  - Effect of Ibuprofen on masking endodontic diagnosis.
AB  - INTRODUCTION: An accurate diagnosis is of upmost importance before initiating
      endodontic treatment; yet, there are occasions when the practitioner cannot
      reproduce the patient's chief complaint because the patient has become
      asymptomatic. Ibuprofen taken beforehand may "mask" or eliminate the patient's
      symptoms. In fact, 64%-83% of patients with dental pain take analgesics before
      seeing a dentist. The purpose of this study was to examine the possible "masking"
      effect of ibuprofen on endodontic diagnostic tests. METHODS: Forty-two patients
      with endodontic pain underwent testing (cold, percussion, palpation, and bite
      force measurement) and then received either placebo or 800 mg ibuprofen. Both
      patients and operators were blinded to the medication received. One hour later,
      diagnostic testing was repeated and compared with pretreatment testing. RESULTS:
      Ibuprofen affected testing values for vital teeth by masking palpation 40%,
      percussion 25%, and cold 25% on affected teeth with symptomatic irreversible
      pulpitis and symptomatic apical periodontitis. There was no observed masking
      effect in the placebo group on palpation, percussion, or cold values. When
      nonvital teeth were included, the masking effect of ibuprofen was decreased.
      However, little masking occurred with the bite force measurement differences.
      CONCLUSIONS: Analgesics taken before the dental appointment can affect endodontic
      diagnostic testing results. Bite force measurements can assist in identifying the
      offending tooth in cases in which analgesics "mask" the endodontic diagnosis.

PMID- 25069909
TI  - Radiographic and clinical outcomes of the treatment of immature permanent teeth
      by revascularization or apexification: a pilot retrospective cohort study.
AB  - INTRODUCTION: This retrospective cohort study compared clinical and radiographic
      outcomes of endodontic treatment performed in immature nonvital permanent teeth
      by apexification (calcium hydroxide or apical barrier with mineral trioxide
      aggregate) versus revascularization. METHODS: A comprehensive chart review was
      performed to obtain a cohort of previously completed cases with recalls. Clinical
      and radiographic data were collected for 31 treated teeth (19 revascularization
      and 12 apexification) with an average follow-up time of 17 months and a recall
      rate of 63%. Tooth survival, success rate, and adverse events were analyzed.
      Changes in radiographic root length, width, and area were quantified. RESULTS:
      The majority of treated teeth survived throughout the study period, with 30 of 31
      (97%) teeth surviving (18/19 [95%] revascularization and 12/12 apexification).
      Most cases were also clinically successful, with 27 of 31 (87%) meeting criteria
      for success (15/19 [78%] revascularization and 12/12 apexification;
      nonsignificant difference). A greater incidence of adverse events was observed in
      the revascularization group (8/19 [42%] vs 1/12 [11%] in apexification) (risk
      ratio = 5.1; P = .04; 95% confidence interval, 0.719-35.48). Although more
      revascularization cases than apexification cases showed an increase in
      radiographic root area and width, the effect was not statistically significant.
      CONCLUSIONS: In this study, revascularization was not superior to other
      apexification techniques in either clinical or radiographic outcomes. Studies
      with large subject cohorts and long follow-up periods are needed to evaluate
      outcomes of revascularization and apexification while accounting for important
      covariants relevant to clinical success.

PMID- 25069910
TI  - Prognostic factors relating to the outcome of endodontic microsurgery.
AB  - INTRODUCTION: The aim of this retrospective study was to evaluate the outcome of
      endodontic microsurgery and to examine prognostic factors related to healing.
      METHODS: The clinical records of all patients who had undergone endodontic
      microsurgery from 1997-2003 at the National Dental Centre of Singapore were
      examined. Teeth with a recall period of 1-2 years were selected. All surgical
      procedures, except for flap raising and suturing, were performed under a surgical
      operating microscope. Root-end cavities prepared with ultrasonic tips were filled
      with Intermediate Restorative Material (Caulk, Milford, DE) or mineral trioxide
      aggregate. Teeth were evaluated for clinical signs and symptoms after surgery.
      Preoperative and postoperative radiographs were evaluated independently by 2
      endodontists. RESULTS: Of 243 root-end surgeries performed, 93 were eligible for
      the study. Outcomes were categorized as healed, healing, or persistent disease;
      78.5% of teeth were assessed to be healed or healing, and 21.5% had persistent
      disease. The percentages of healed and healing teeth for anterior and posterior
      root-end surgeries were 76.5% and 80.4%, respectively, with no significant
      difference in the procedures (P = .8). Ordinal logistic regression showed a
      higher likelihood of healing in females compared with males (P = .001) and
      maxillary anterior teeth compared with mandibular anterior teeth (P = .03).
      Preoperative probing depths of <=3 mm were significantly associated with healing
      (P = .05). CONCLUSIONS: The use of modern endodontic surgical techniques resulted
      in 78.5% healed and healing teeth with a recall period of 1-2 years. Prognostic
      factors affecting successful healing include sex, tooth type, and preoperative
      probing depths.

PMID- 25069911
TI  - 5-year results comparing mineral trioxide aggregate and adhesive resin composite
      for root-end sealing in apical surgery.
AB  - INTRODUCTION: Recent meta-analyses of the outcome of apical surgery using modern
      techniques including microsurgical principles and high-power magnification have
      yielded higher rates of healing. However, the information is mainly based on 1-
      to 2-year follow-up data. The present prospective study was designed to re
      examine a large sample of teeth treated with apical surgery after 5 years.
      METHODS: Patients were recalled 5 years after apical surgery, and treated teeth
      were classified as healed or not healed based on clinical and radiographic
      examination. (The latter was performed independently by 3 observers). Two
      different methods of root-end preparation and filling (primary study parameters)
      were to be compared (mineral trioxide aggregate [MTA] vs adhesive resin composite
      [COMP]) without randomization. RESULTS: A total of 271 patients and teeth from a
      1-year follow-up sample of 339 could be re-examined after 5 years (dropout rate =
      20.1%). The overall rate of healed cases was 84.5% with a significant difference
      (P = .0003) when comparing MTA (92.5%) and COMP (76.6%). The evaluation of
      secondary study parameters yielded no significant difference for healing outcome
      when comparing subcategories (ie, sex, age, type of tooth treated, post/screw,
      type of surgery). CONCLUSIONS: The results from this prospective nonrandomized
      clinical study with a 5-year follow-up of 271 teeth indicate that MTA exhibited a
      higher healing rate than COMP in the longitudinal prognosis of root-end sealing.

PMID- 25069912
TI  - The role of insurance and training in dental decision making.
AB  - INTRODUCTION: The purpose of this investigation was to evaluate (1) the
      differences in treatment planning decisions between dental general practitioners
      and specialists and (2) the role of patients' insurance and/or type of treatment
      in decision making. METHODS: One hundred eighty subject charts were selected from
      1,740 dental charts. Two specialists examined radiographs and reviewed the charts
      and then independently generated treatment plans. If there was disagreement
      between the 2 specialists, they discussed all aspects of the case until a
      consensus was reached. RESULTS: Four subjects were excluded. Thus, 176 patients
      were evaluated. A statistically significant difference (chi(2) = 202.303, P =
      .0001) was found between treatment plans designed by GPs and those designed by
      specialists. Patients' insurance status did not influence the degree of agreement
      between specialists and GPs. The odds ratio for Medicaid was 0.431 (95%
      confidence interval [CI], 0.103-1.801; P = .249), and for self-pay, it was 0.801
      (95% CI, 0.328-1.955; P = .627). However, logistic regression analysis showed
      that the type of treatment plan designed by GPs (ie, endodontic treatment,
      endodontic retreatment, and extraction followed by implant placement) was
      significantly related to the degree of disagreement with the specialists (odds
      ratio = 4.522; 95% CI, 1.378-14.84; P = .013). CONCLUSIONS: Insurance did not
      play a role in the decision-making portion of the treatment plan. However, the
      type of treatment was found to be significant. Implant cases had the highest
      disagreement between the specialists and the general dentists.

PMID- 25069913
TI  - Effects of glutamine on proliferation, migration, and differentiation of human
      dental pulp cells.
AB  - INTRODUCTION: Although glutamine (Gln) is mitogenic in various cell types, little
      is known about its role in human dental pulp cells (HDPCs). This study
      investigated the effects of Gln on proliferation, migration, and odontoblastic
      differentiation of HDPCs and the underlying signal pathway mechanisms. METHODS:
      Growth and migration were assessed by cell counting and colorimetric cell
      migration kits. Differentiation was measured as alkaline phosphatase activity,
      calcified nodule formation by alizarin red staining, and marker mRNA expression
      by reverse transcriptase-polymerase chain reaction (RT-PCR). Chemokine expression
      was also evaluated by RT-PCR. Signal transduction pathways were examined by RT
      PCR and Western blot analysis. RESULTS: Gln dose-dependently increased
      proliferation, migration, alkaline phosphatase activity, mineralized nodule
      formation, and odontoblast-marker mRNA of HDPCs. Gln also up-regulated expression
      of interleukin-6, interleukin-8, MCP-1, MIP-3alpha, CCL2, CCL20, and CXCL1. Gln
      increased BMP-2 and BMP-4 mRNA, phosphorylation of Smad 1/5/8, beta-catenin, and
      key proteins of the Wnt signaling pathway. Furthermore, Gln resulted in up
      regulation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal
      kinase. In addition, noggin, DKK1, inhibitors of p38, ERK, and JNK significantly
      attenuatted Gln-induced growth, migration, and odontoblastic differentiation.
      CONCLUSIONS: Collectively, this study demonstrated that Gln promoted growth,
      migration, and differentiation in HDPCs through the BMP-2, Wnt, and MAPK
      pathways, leading to improved pulp repair and regeneration.

PMID- 25069914
TI  - Apical constriction: location and dimensions in molars-a micro-computed
      tomography study.
AB  - INTRODUCTION: The existence of the apical constriction has been repeatedly
      questioned. The aim of the present study was to validate the existence of the
      apical constriction and determine its location and dimensions in molars by using
      substantial micro-computed tomography analysis. METHODS: Ninety human molars with
      271 canals were evaluated. Teeth with resorption, defects, or incomplete root
      formation as well as wisdom teeth were excluded. Patients' age was categorized
      into 3 groups. Teeth were scanned by micro-computed tomography with a resolution
      of 27 MUm. Multi-threshold segmentation was performed to trace the canal outline
      in a total of 25,093 sections. In each cross section, 88 parameters, eg, area,
      circumference, and maximum and minimum diameter were recorded and analyzed. The
      apical constriction (AC) was defined to be the narrowest area extending along a
      distance of 0.1 mm or more at the apex. Size and form of the constriction were
      recorded as well as the distance to the apical foramen (AC-AF) and apex (AC-A).
      RESULTS: The mean distance of AC-AF was 0.2 mm (99% confidence interval, 0.15
      0.24; range, 0-0.6 mm), and of AC-A it was 0.9 mm (99% confidence interval, 0.86
      1.0; range, 0.1-1.7 mm). The type of canal had no influence on AC-AF and AC-A. In
      76% of all canals the apical constriction was parallel. The mean size of
      constriction in molars was instrument size 30. Patients aged 30 or younger had
      significantly wider constrictions. CONCLUSIONS: The apical constriction was found
      to be located at or close to the foramen. The most common form was the parallel
      form.

PMID- 25069915
TI  - Effects of deferoxamine on the repair ability of dental pulp cells in vitro.
AB  - INTRODUCTION: In previous studies, we found that hypoxia promoted the
      mineralization of dental pulp cells (DPCs). However, the clinical application of
      hypoxia as a therapy is questionable or unfeasible. Deferoxamine (DFO), a
      medication for iron overload, has also been shown to induce hypoxia. The purpose
      of this study was to investigate the effects of DFO on the repair ability of
      DPCs. METHODS: DPCs were obtained by using a tissue explant technique in vitro
      and were treated with different concentrations of DFO or hypoxia culture for 2
      days. The viability, proliferation, migration, and odontogenic differentiation of
      DPCs were assayed and analyzed. The expression of hypoxia-inducible factor 1
      alpha (HIF-1alpha) was assessed through Western blotting. RESULTS: Ten
      micromolars of DFO enhanced the expression of HIF-1alpha similarly to hypoxia and
      did not affect the viability of DPCs for 2 days. Furthermore, the proliferation,
      migration, and odontogenic differentiation of DPCs were promoted by DFO.
      CONCLUSIONS: These results suggest that DFO might improve the repair ability of
      DPCs by HIF-1alpha.

PMID- 25069916
TI  - Effect of verapamil, a calcium channel blocker, on the odontogenic activity of
      human dental pulp cells cultured with silicate-based materials.
AB  - INTRODUCTION: This study examines how calcium silicate cement extracts influence
      the behavior of human dental pulp cells (hDPCs) through calcium channels and
      active mitogen-activated protein kinase pathways, in particular extracellular
      signal-related kinase (ERK). METHODS: HDPCs are treated with various silicon
      concentrations both with and without verapamil, after which the cells' viability
      and odontogenic differentiation markers are determined by using PrestoBlue assay
      and Western blot, respectively. RESULTS: The silicon promoted cell proliferation
      and inhibited calcium channel blockers. It was also found that silicon increased
      ERK and p38 activity in a dose-dependent manner. Furthermore, it raised the
      expression and secretion of alkaline phosphatase, osteocalcin, dentin
      sialophosphoprotein, and dentin matrix protein-1. In addition, statistically
      significant differences (P < .05) have been found in the secretion of osteocalcin
      in ERK inhibitor + verapamil between the silicon concentrations; these varations
      are dose-dependent and indicate that ERK signaling is involved in the silicon
      induced odontogenic differentiation of hDPCs. CONCLUSIONS: The current study
      shows that silicon ions released from calcium silicate substrates play a key role
      in odontoblastic differentiation of hDPCs through calcium channels and modulate
      ERK activation.

PMID- 25069917
TI  - Prostaglandin transporting protein-mediated prostaglandin E2 transport in
      lipopolysaccharide-inflamed rat dental pulp.
AB  - INTRODUCTION: The prostaglandin transporter (Pgt) and multidrug resistance
      associated protein (Mrp) 4 are membrane transport proteins that play crucial
      roles in the transmembrane uptake and/or efflux of prostaglandins (PGs). This
      study attempted to analyze the protein expression of Pgt and Mrp4 and their
      involvement in PGE2 efflux transport in lipopolysaccharide (LPS)-inflamed rat
      incisor pulp tissue. METHODS: Pulpitis was induced in the upper incisors of
      Wistar rats by treating them with LPS for 24 hours. The protein expression levels
      of Pgt, Mrp4, and microsomal PGE synthase (mPGES) were analyzed with
      immunofluorescent staining. The amount of PGE2 released from the inflamed pulp
      tissue in the presence or absence of dipyridamole (an Mrp4 inhibitor) was
      assessed by using an enzyme-linked immunosorbent assay. RESULTS: Double
      immunofluorescence staining revealed that the Pgt, Mrp4, and mPGES
      immunoreactivity co-localized in CD31-expressing endothelial cells. Moreover, the
      Mrp4 inhibitor caused a significant decrease in the amount of PGE2 released from
      the LPS-inflamed pulp (P < .01 at 24 hours). CONCLUSION: Pgt, Mrp4, and mPGES
      expression was detected in the endothelial cells of normal and LPS-inflamed rat
      incisor pulp tissue, suggesting that these cells are associated with the
      biosynthesis and transmembrane transport of PGE2. The significant decrease in
      PGE2 release induced by the Mrp4 inhibitor suggests that Mrp4 contributes to the
      transport of PGE2 in the transmembrane efflux pathway.

PMID- 25069918
TI  - A comparative study of BioAggregate and ProRoot MTA on adhesion, migration, and
      attachment of human dental pulp cells.
AB  - INTRODUCTION: The aim of the present study was to evaluate the effects of a novel
      bioceramic nanoparticular cement, BioAggregate (Innovative Bioceramix, Vancouver,
      BC, Canada), on the adhesion, migration, and attachment of human dental pulp
      cells (HDPCs) and to compare its performance with that of ProRoot mineral
      trioxide aggregate (MTA) (Dentsply, Tulsa, OK). METHODS: Primary cultured HDPCs
      were treated with various dilutions of BioAggregate and MTA extracts to assess
      the cell viability using the Cell Counting Kit-8 (Dojindo, Kumamoto, Japan). Cell
      adhesion assay was performed using type I collagen-coated plates. An in vitro
      scratch wound healing model was used to determine cell migration. Focal adhesion
      formation and cytoskeleton organization were further examined by double
      immunofluorescence labeling for vinculin and fibrous actin. To assess cell
      attachment, HDPCs were directly seeded onto the material surfaces and observed by
      scanning electron microscopy. RESULTS: HDPCs exposed to BioAggregate extracts
      showed the highest viabilities at all extract concentrations at 24 and 48 hours,
      whereas cells exposed to original MTA extracts displayed suppressed viabilities
      at 72 hours compared with the control. Treatment with BioAggregate extracts
      enhanced cellular adhesion and migration of HDPCs in a concentration-dependent
      manner, which was superior to the effects induced by MTA extracts.
      Immunofluorescence staining indicated that both BioAggregate and MTA optimized
      focal adhesion formation and stress fiber assembly. Furthermore, scanning
      electron microscopic analysis revealed that HDPCs attached onto BioAggregate were
      more flattened and exhibited better spreading than cells on MTA. CONCLUSIONS:
      BioAggregate is able to promote cellular adhesion, migration, and attachment of
      HDPCs, indicating its excellent cytocompatibility. Therefore, BioAggregate
      appears to be a possible alternative to MTA for pulp capping.

PMID- 25069919
TI  - Odontogenic effect of a fast-setting pozzolan-based pulp capping material.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) is widely used as a pulp capping
      material. Recently, a MTA-derived fast-setting pozzolan cement (Endocem; Maruchi,
      Wonju, Korea) was introduced in the endodontic field. Our aim in this study was
      to investigate the odontogenic effects of this cement in vitro and in vivo.
      METHODS: Human dental pulp cells (hDPCs) were cultured, and the effects of
      Endocem and a previously marketed MTA (ProRoot; Dentsply, Tulsa, OK) on
      biocompatibility were evaluated by assessing cell morphology and performing a
      cell viability test. Chemical composition of each material was analyzed by energy
      dispersive X-ray spectroscopic analysis. Odontoblastic differentiation was
      analyzed by alkaline phosphatase activity and alizarin red S staining. The
      expression of odontogenic-related markers, namely dentin sialophosphoprotein,
      dentin matrix protein 1, and osteonectin, was evaluated by real-time polymerase
      chain reaction, Western blotting, and immunofluorescence analysis. Pinpoint pulp
      exposures were made on rat teeth and then capped with ProRoot or Endocem. After 4
      weeks, reparative tertiary dentin formation and inflammatory responses were
      investigated histologically. RESULTS: The biocompatibility of Endocem was similar
      to that of ProRoot. Energy-dispersive X-ray spectroscopic analysis showed that
      ProRoot and Endocem contained similar elemental constituents such as calcium,
      oxygen, and silicon. Alkaline phosphatase activity and mineralized nodule
      formation increased in ProRoot- and Endocem-treated cells compared with medium
      only-treated cells in the control group (P < .05). The expression of odontogenic
      related markers was significantly higher in the ProRoot- and Endocem-treated
      groups than the control group (P < .05), but there was no significant difference
      in the expression of these markers between the 2 experimental groups (P > .05).
      Four weeks after the pulp capping procedure, continuous tertiary dentin had
      formed directly underneath the capping materials and the pulp exposure area in
      all samples in the 2 treated groups. Furthermore, most specimens either had no
      inflammation or minor pulpal inflammation. CONCLUSIONS: Our results indicate that
      ProRoot and Endocem have similar biocompatibility and odontogenic effects.
      Therefore, Endocem is as effective a pulp capping material as ProRoot.

PMID- 25069921
TI  - Blood profile and histology in oral infections associated with diabetes.
AB  - INTRODUCTION: We aimed to investigate the relationship between blood profile and
      histologic findings in both apical periodontitis (AP) and periodontal disease
      (PD) associated with diabetes. METHODS: Wistar rats (N = 80) were assigned to the
      following 8 groups: control, AP, PD, AP associated with PD, diabetes, diabetes
      with AP, diabetes with PD, and diabetes with AP and PD. Diabetes mellitus (DM)
      was induced with streptozotocin, AP was induced by exposure to the oral
      environment, and PD was induced using periodontal ligature. After 30 days, blood
      samples were collected, and the rats were euthanized. Subsequently, the maxillae
      were processed for light microscopy. Hematologic examinations were conducted to
      determine the total number of erythrocytes and leukocytes, erythrocyte constant,
      and blood glucose level. One-way analysis of variance and Kruskal-Wallis tests
      were used for statistical analysis, and the significance was set at P < .05.
      RESULTS: A significant correlation was found between the histologic findings and
      blood parameters. CONCLUSIONS: In conclusion, diabetes accelerated the
      development and progression of AP and PD in the rats and caused an increase in
      the average erythrocyte volume as well as the leukocyte and neutrophil counts.
      Oral infections increase the total number of leukocytes, the number of
      neutrophils and lymphocytes, and blood glucose concentrations in DM rats.

PMID- 25069920
TI  - EZH2, a potential regulator of dental pulp inflammation and regeneration.
AB  - INTRODUCTION: Dental pulp has limited capability to regenerate, which happens in
      the early stage of pulpitis. An ambiguous relationship exists; inflammation may
      impair or support pulp regeneration. Epigenetics, which is involved in cell
      proliferation and inflammation, could regulate human dental pulp cell (HDPCs)
      regeneration. The aim of this study was to determine the role of the epigenetic
      mark, enhancer of zeste homolog 2 (EZH2), in the inflammation, proliferation, and
      regeneration of dental pulp. We used trimethylated histone H3 lysine 27(H3K27me3)
      and its lysine demethylase 6B (KDM6B) to monitor functional effects of altered
      EZH2 levels. METHODS: We detected epigenetic marks (EZH2, H3K27me3, and KDM6B) in
      pulp tissue by immunohistochemistry and immunofluorescence. EZH2 levels in HDPCs
      in inflammatory responses or differentiation were analyzed by quantitative
      polymerase chain reaction and Western blot. Quantitative polymerase chain
      reaction was used to assess the effects of EZH2 inhibition on interleukins in
      HDPCs upon tumor necrosis factor alpha stimulation. Cell proliferation was tested
      by cell counting kit-8, cell cycle, and apoptosis analysis. HDPC differentiation
      was investigated by quantitative polymerase chain reaction, alkaline phosphatase
      activity, and oil red O staining. RESULTS: EZH2 and H3K27me3 were decreased,
      whereas KDM6B was increased in infected pulp tissue and cells, which were similar
      to HDPC differentiation. EZH2 inhibition suppressed IL-1b, IL-6, and IL-8
      messenger RNA (mRNA) in HDPCs upon inflammatory stimuli and impeded HDPC
      proliferation by decreasing cell number, arresting cell cycle, and increasing
      apoptosis. Suppressed EZH2 impaired adipogenesis, peroxisome proliferator
      activated receptor r (PPAR-r), and CCAAT-enhancer binding protein a (CEBP/a) mRNA
      in adipogenic induction while enhancing alkaline phosphatase activity, Osx, and
      bone sialoprotein (BSP) mRNA in mineralization induction of HDPCs. CONCLUSIONS:
      EZH2 inhibited HDPC osteogenic differentiation while enhancing inflammatory
      response and proliferation, suggesting its role in pulp inflammation,
      proliferation, and regeneration.

PMID- 25069922
TI  - Effective analysis of the use of peracetic acid after instrumentation of root
      canals contaminated with Enterococcus faecalis.
AB  - INTRODUCTION: The aim of this study was to evaluate the effectiveness of
      peracetic acid (PAA) in cleaning root canals contaminated with Enterococcus
      faecalis. METHODS: Sixty first and second mandibular molars were used. Their
      mesiobuccal canals were prepared with the Reciproc System (VDW, Munich, Germany).
      The canals were irrigated with 10 mL saline during instrumentation. The teeth
      were randomly divided into 3 groups (n = 20), according to the irrigation
      solution to be used after instrumentation: group PAA (5 mL 1% PAA), group
      EDTA/sodium hypochlorite (NaOCl) (5 mL 17% EDTA followed by 5 mL 2.5% sodium
      hypochlorite), and group S (5 mL saline). Microbiological samples were collected
      before instrumentation and after final irrigation. Bacterial quantification was
      performed by counting the number of colony-forming units (CFUs/mL). The results
      were analyzed by the nonparametric Wilcoxon and Kruskal-Wallis tests. RESULTS:
      The 3 groups showed a significant reduction (P < .05) in CFUs/mL after final
      irrigation. PAA and NaOCl associated with EDTA produced a significantly higher
      reduction in CFUs/mL (P < .05) compared with saline. There was no statistically
      significant difference between PAA and EDTA + 2.5% NaOCl (P > .05). CONCLUSIONS:
      According to the results of the present study, the effectiveness of 1% PAA was
      similar to that of 17% EDTA + 2.5% NaOCl in cleaning curved root canals
      contaminated with E. faecalis.

PMID- 25069923
TI  - Response of human osteoblastic and osteoclastic cells to AH plus and pulp canal
      sealer containing quaternary ammonium polyethylenimine nanoparticles.
AB  - INTRODUCTION: The incorporation of quaternary ammonium polyethylenimine (QPEI)
      nanoparticles into endodontic sealers induces alterations in their structure and
      surface properties, which may affect the compatibility with the periapical
      tissues. This work addressed the behavior of human bone cells exposed to extracts
      from commercial and QPEI containing AH Plus (DeTrey, Konstanz, Germany) and Pulp
      Canal Sealer EWT (PCS; Kerr Italia Srl, Salerno, Italy). METHODS: Freshly mixed
      AH Plus and PCS or containing 2% QPEI (0.3 mL spread over the well bottom of a 24
      well plate) were extracted with culture medium (1.5 mL for 24 hours at 37 degrees
      C) and diluted (1:20-1:5000). Osteoblastic or osteoclastic cells were cultured in
      the presence of QPEI particles (1%-10%) and were exposed to the extracts from
      unmodified and QPEI containing sealers. RESULTS: QPEI nanoparticles, at 1% and
      2%, did not affect cell behavior. On osteoblastic cells, AH Plus and PCS
      increased DNA at 1:2500 dilution (levels <=1:100 were cytotoxic). Alkaline
      phosphatase activity decreased at dilutions <=1:500. Comparatively, QPEI
      containing AH Plus increased DNA at 1:2500 and 1:500 dilutions, and QPEI
      containing PCS induced ALP activity at 1:2500 and 1:500 dilutions. Regarding
      osteoclastic cells, DNA increased (AH Plus) or was not affected (PCS) at
      dilutions up to 1:500 and decreased with more concentrated extracts. Tartrate
      resistant acid phosphatase activity decreased with dilutions <=1:500 for both
      sealers. QPEI containing sealers presented a similar behavior. The sealers
      affected some intracellular signaling pathways, and QPEI containing sealers
      further modulate these mechanisms. CONCLUSIONS: QPEI nanoparticles, at 2%, did
      not affect cell behavior. However, the incorporation of 2% QPEI particles into AH
      Plus and PCS modulates the proliferation and differentiation of bone cells,
      depending on the sealer and the cell type, without increasing the sealers'
      cytotoxicity.

PMID- 25069924
TI  - In vitro cytotoxicity of guttaflow 2 on human gingival fibroblasts.
AB  - INTRODUCTION: The primary aim of this study was to evaluate the cytotoxic effects
      of GuttaFlow 2 (Coltene Whaledent, GmBH+Co KG, Langenau, Switzerland) on human
      gingival fibroblasts (HGFs). METHODS: Samples of the test materials GuttaFlow 2,
      mineral trioxide aggregate (MTA), AH Plus (Dentsply DeTrey, Konstanz, Germany),
      and RealSeal sealer (SybronEndo, Orange, CA) were fabricated in cylindrical
      nonreactive plastic tubes of 3-mm diameter and 2-mm height. Extracts of freshly
      mixed and set samples were prepared using the ratio of 0.5 cm(2)/mL, 1 cm(2)/mL,
      and 1.5 cm(2)/mL according to ISO 10993 series. The extracts were incubated with
      HGF cells for 24 and 72 hours. A cell counting kit-8 assay (Dojindo, Kumamoto,
      Japan) assay was used to examine cytotoxicity. The results were analyzed with the
      independent t test and 1-way analysis of variance test (P < .05). RESULTS: At all
      experimental conditions, the extracts of freshly mixed GuttaFlow 2 were nontoxic,
      whereas the extracts of freshly mixed and set AH Plus and RealSeal sealers were
      toxic to HGF cells (P < .05). The extracts of set GuttaFlow 2 were toxic at 72
      hours (P < .05) and nontoxic at 24 hours. The extracts of freshly mixed MTA were
      nontoxic at both time points. For the extracts of set MTA, 1.5 cm(2)/mL was toxic
      at 72 hours and 1.5 cm(2)/mL and 1 cm(2)/mL were toxic at 24 hours (P < .05).
      CONCLUSIONS: Both GuttaFlow 2 and MTA evoked a less toxic response to HGF cells
      than AH Plus and RealSeal sealer.

PMID- 25069925
TI  - Impacts of conservative endodontic cavity on root canal instrumentation efficacy
      and resistance to fracture assessed in incisors, premolars, and molars.
AB  - INTRODUCTION: Conservative endodontic cavity (CEC) may improve fracture
      resistance of teeth but compromise the instrumentation of canals. This study
      assessed the impacts of CEC on both variables in 3 tooth types. METHODS:
      Extracted human intact maxillary incisors, mandibular premolars, and molars (n =
      20/type) were imaged with micro-computed tomographic imaging (20-MUm resolution)
      and assigned to CEC or traditional endodontic cavity (TEC) groups (n =
      10/group/type). Minimal CECs were plotted on scanned images. Canals were prepared
      with WaveOne instruments (Dentsply Maillefer, Ballaigues, Switzerland) using
      1.25% sodium hypochlorite and post-treatment micro-computed tomographic images
      obtained. The proportion of the untouched canal wall (UCW) and the dentin volume
      removed (DVR) for each tooth type was analyzed with the independent-samples t
      test. The 60 instrumented and 30 intact teeth (negative control, n = 10/type)
      were loaded to fracture in the Instron Universal Testing machine (Instron,
      Canton, MA) (1 mm/min), and the data were analyzed with 1-way analysis of
      variance and the Tukey test. RESULTS: The mean proportion of UCW was
      significantly higher (P < .04) only in the distal canals of molars with CEC
      (57.2% +/- 21.7%) compared with TEC (36.7% +/- 17.2%). The mean DVR was
      significantly smaller (P < .003) for CEC than for TEC in incisors (16.09 +/- 4.66
      vs 23.24 +/- 3.38 mm(3)), premolars (8.24 +/- 1.64 vs 14.59 +/- 4.85 mm(3)), and
      molars (33.37 +/- 67.71 mm(3)). The mean load at fracture for CEC was
      significantly higher (P < .05) than for TEC in premolars (586.8 +/- 116.9 vs
      328.4 +/- 56.7 N) and molars (1586.9 +/- 196.8 vs 641.7 +/- 62.0 N). In both
      tooth types, CEC did not differ significantly from the negative controls.
      CONCLUSIONS: Although CEC was associated with the risk of compromised canal
      instrumentation only in the molar distal canals, it conserved coronal dentin in
      the 3 tooth types and conveyed a benefit of increased fracture resistance in
      mandibular molars and premolars.

PMID- 25069926
TI  - Antibiofilm effects of endodontic sealers containing quaternary ammonium
      polyethylenimine nanoparticles.
AB  - INTRODUCTION: This study evaluated the antibiofilm effects of 2 endodontic
      sealers incorporated with quaternary ammonium polyethylenimine (QPEI)
      nanoparticles at a 2% concentration (w/w). METHODS: The materials tested were AH
      Plus and Pulp Canal Sealer EWT (PCS) in the commercial unmodified form or
      containing 2% QPEI. Antibiofilm assays were conducted by using direct-contact and
      membrane-restricted tests for evaluation of bacterial viability in biofilms grown
      onto membranes or paper disks and the crystal violet microtiter-plate assay to
      evaluate the effects of sealer extracts on the biofilm biomass. Two Enterococcus
      faecalis strains (ATCC and an endodontic isolate) were used. RESULTS: Direct
      contact and membrane-restricted antibiofilm tests revealed that PCS 2% was the
      only material to promote total killing of E. faecalis ATCC biofilms. All the
      materials significantly reduced bacterial counts in E. faecalis ATCC biofilms
      when compared with the positive control in both tests (P < .05). In the direct
      test against E. faecalis RW35, PCS 2% was significantly more effective than the
      other materials and was the only one that showed significantly lower counts than
      the positive control (P < .05). In the crystal violet assay, only AH Plus 2%
      presented optical density readings significantly lower than the positive control
      of the ATCC strain (P < .05). No other significant effects on the biofilm biomass
      of the 2 E. faecalis strains were observed for any of the sealers tested (P >
      .05). CONCLUSIONS: Addition of QPEI nanoparticles improved the killing ability of
      PCS against biofilms of both E. faecalis strains and the effects of AH Plus on
      the biomass of biofilms from the ATCC strain.

PMID- 25069927
TI  - Evaluation of triple antibiotic paste removal by different irrigation procedures.
AB  - INTRODUCTION: Regenerative endodontics aims to re-establish a functional pulp
      dentin complex. First, the root canal system is disinfected primarily by
      irrigants and medicaments. Triple antibiotic paste (TAP), a commonly used
      intracanal medicament, has been shown to be directly toxic to stem cells at
      concentrations greater than 0.1 g/mL. Thus, its complete removal is a crucial
      step in regenerative endodontic procedures. We hypothesized that currently used
      irrigation techniques do not completely remove TAP from root canal system.
      METHODS: TAP was radiolabeled by the incorporation of I(125), and calcium
      hydroxide (Ultracal; Ultradent, South Jordan, UT) was radiolabeled with Ca(45).
      The intracanal medicaments were placed into standardized human root segments and
      incubated for 28 days at 37 degrees C. Then, canals were irrigated with
      EndoActivator (Dentsply, Tulsa, OK), passive ultrasonic irrigation, EndoVac
      (SybronEndo, Coppell, TX), or a syringe/Max-i-Probe needle (Dentsply Rinn, Elgin,
      IL) using a standardized irrigation protocol in a closed system. Radioactivity
      levels (counts per minute values) were measured for each tooth before and after
      the irrigation protocols. Furthermore, the canals were sequentially enlarged and
      dentin samples collected and evaluated for radioactivity. Data were analyzed with
      analysis of variance and Bonferroni post hoc testing (P < .05). RESULTS:
      Approximately 88% of the TAP was retained in the root canal system regardless of
      the irrigation technique used (no difference among groups). Furthermore,
      approximately 50% of the radiolabeled TAP was present circumferentially up to 350
      MUm within the dentin. Conversely, up to 98% of the radiolabeled intracanal
      calcium hydroxide was removed, and most residual medicament was found present in
      the initial 50 MUm of dentin. CONCLUSIONS: Current irrigation techniques do not
      effectively remove TAP from root canal systems, possibly because of its
      penetration and binding into dentin. However, calcium hydroxide is effectively
      removed with significant less residual presence.

PMID- 25069928
TI  - Tissue dissolution by a novel multisonic ultracleaning system and sodium
      hypochlorite.
AB  - INTRODUCTION: This study aimed to evaluate the effectiveness of a novel
      Multisonic Ultracleaning System (Sonendo Inc, Laguna Hills, CA) in tissue
      dissolution in comparison with conventional irrigation devices. METHODS: Pieces
      of bovine muscle tissue (68 +/- 2 mg) were placed in 0.7-mL test tubes (height:
      23.60 mm, inner diameter: 6.00 mm, outer diameter: 7.75 mm) and exposed to 5
      minutes of irrigation by different devices. Endodontic devices included the
      Multisonic Ultracleaning System, the Piezon Master 700 (EMS, Dallas, TX)
      ultrasonic system with agitation, the EndoVac negative-pressure irrigation system
      (SybronEndo, Orange, CA), and a conventional positive-pressure 27-G irrigation
      needle at a flow rate of 10 mL/min. The systems were tested with 0.5%, 3%, and 6%
      sodium hypochlorite (NaOCl) at room temperature (21 degrees C) as well as 40
      degrees C. Irrigation with sterile water was used as a control. The mass of
      tissue specimens was measured and recorded before and after the use of each
      device, and if the specimen was completely dissolved visually within 5 minutes,
      the dissolution time was recorded. The rate of tissue dissolution (%/s) was then
      calculated. RESULTS: The Multisonic Ultracleaning System had the fastest rate of
      tissue dissolution (P < .05), at 1.0% +/- 0.1% per second using 0.5% NaOCl, 2.3%
      +/- 0.9% per second using 3% NaOCl, and 2.9% +/- 0.7% per second using 6% NaOCl.
      This tissue dissolution rate was more than 8 times greater than the second
      fastest device tested (P < .01), the Piezon Master 700 ultrasonic system, which
      resulted in a tissue dissolution rate of 0.328% +/- 0.002% per second using 6%
      NaOCl at 40 degrees C. For all irrigation devices tested, the rate of tissue
      dissolution increased with a higher concentration and temperature of the NaOCl
      solution. CONCLUSIONS: The novel Multisonic Ultracleaning System achieved a
      significantly faster tissue dissolution rate when compared with the other systems
      examined in vitro.

PMID- 25069929
TI  - Comparison of cyclic fatigue resistance of nickel-titanium coronal flaring
      instruments.
AB  - INTRODUCTION: The purpose of this study was to compare the cyclic fatigue
      resistance of coronal flaring instruments. METHODS: Three groups of nickel
      titanium (NiTi) endodontic coronal flaring instruments were tested in steel
      canals with a 3-mm curvature radius and 60 degrees  (n = 18) and 45 degrees  of
      curvature (n = 18). The cyclic fatigue of the following NiTi instruments was
      tested: ProTaper Sx (Dentsply Maillefer, Ballaigues, Switzerland), HyFlex 25.08
      (Coltene-Whaledent, Allstetten, Switzerland), and Revo-S SC1 (Micro-Mega,
      Besancon, France). The length and diameter of the fractured fragment and the
      total area of the fractured surface of each instrument were measured. The data
      were then statistically analyzed using a 1-way analysis of variance and the post
      hoc Tukey test (alpha = .05). RESULTS: At the 60 degrees  of curvature, Revo-S
      had the highest fatigue resistance, HyFlex had the second highest fatigue
      resistance, and ProTaper Universal had the least fatigue resistance. At the 45
      degrees  of curvature, the Revo-S and HyFlex showed superior cyclic fatigue
      resistance compared with the ProTaper. The length of the fracture fragment of the
      ProTaper instrument was longer than that of the other groups at the 60 degrees 
      of curvature. At the 45 degrees  of curvature, the length of the fracture
      fragment of the ProTaper and HyFlex instruments was longer than that of Revo-S.
      The mean diameter and surface area of the HyFlex instruments in the fractured
      part was higher than that of other groups at both angles of curvature.
      CONCLUSIONS: The Revo-S SC1 and HyFlex 25.08 instruments showed better cyclic
      fatigue resistance than the ProTaper Sx instrument.

PMID- 25069930
TI  - Shaping ability of the conventional nickel-titanium and reciprocating nickel
      titanium file systems: a comparative study using micro-computed tomography.
AB  - INTRODUCTION: This study used micro-computed tomographic imaging to compare the
      shaping ability of Mtwo (VDW, Munich, Germany), a conventional nickel-titanium
      file system, and Reciproc (VDW), a reciprocating file system morphologically
      similar to Mtwo. METHODS: Root canal shaping was performed on the mesiobuccal and
      distobuccal canals of extracted maxillary molars. In the RR group (n = 15),
      Reciproc was used in a reciprocating motion (150 degrees  counterclockwise/30
      degrees  clockwise, 300 rpm); in the MR group, Mtwo was used in a reciprocating
      motion (150 degrees  clockwise/30 degrees  counterclockwise, 300 rpm); and in the
      MC group, Mtwo was used in a continuous rotating motion (300 rpm). Micro-computed
      tomographic images taken before and after canal shaping were used to analyze
      canal volume change and the degree of transportation at the cervical, middle, and
      apical levels. The time required for canal shaping was recorded. Afterward, each
      file was analyzed using scanning electron microscopy. RESULTS: No statistically
      significant differences were found among the 3 groups in the time for canal
      shaping or canal volume change (P > .05). Transportation values of the RR and MR
      groups were not significantly different at any level. However, the transportation
      value of the MC group was significantly higher than both the RR and MR groups at
      the cervical and apical levels (P < .05). In the scanning electron microscopic
      analysis, file deformation was observed for 1 file in group RR (1/15), 3 files in
      group MR (3/15), and 5 files in group MC (5/15). CONCLUSIONS: In terms of shaping
      ability, Mtwo used in a reciprocating motion was not significantly different from
      the Reciproc system.

PMID- 25069931
TI  - Evaluation of the resistance to cyclic fatigue among ProTaper Next, ProTaper
      Universal, and Vortex Blue rotary instruments.
AB  - INTRODUCTION: The purpose of this study was to compare the fracture resistance to
      cyclic fatigue of ProTaper Next (PTN; Dentsply Tulsa Dental Specialties, Tulsa,
      OK), ProTaper Universal (PTU, Dentsply Tulsa Dental Specialties), and Vortex Blue
      (VB, Dentsply Tulsa Dental Specialties) rotary instruments. METHODS: Twenty
      instruments each of PTN X1-X5, PTU S1-F5, and VB 20/04-50/04 were rotated until
      fracture in a simulated canal of 90 degrees  and a 5-mm radius using a custom
      made testing platform. The number of cycles to fracture (NCF) was calculated.
      Weibull analysis was used to predict the maximum number of cycles when 99% of the
      instrument samples survive. RESULTS: VB 20/04-30/04 had significantly higher NCF
      than PTU S1-F5 and PTN X1-X5. VB 35/04-45/04 had significantly higher NCF than
      PTU S2-F5 and PTN X2-X5. PTN X1 had higher NCF than PTU S1-F5. PTN X2 had higher
      NCF than PTU F2-F5. The Weibull distribution predicted the highest number of
      cycles at which 99% of instruments survive to be 766 cycles for VB 25/04 and the
      lowest to be 50 cycles for PTU F2. CONCLUSIONS: Under the limitations of this
      study, VB 20/04-45/04 were more resistant to cyclic fatigue than PTN X2-X5 and
      PTU S2-F5. PTN X1 and X2 were more resistant to cyclic fatigue than PTU F2-F5.
      The Weibull distribution appears to be a feasible and potentially clinically
      relevant model to predict resistance to cyclic fatigue.

PMID- 25069933
TI  - Effects of sonic application of adhesive systems on bonding fiber posts to root
      canals.
AB  - INTRODUCTION: Luting posts inside the root canal is still a challenge because of
      the difficulty of bonding adhesive materials in the apical third of roots. This
      study evaluated the effect of the application mode of 3 simplified etch-and-rinse
      adhesives on the push-out bond strength (PBS), nanoleakage (NL), and in situ
      degree of conversion (DC) of fiber posts in the root canal. METHODS: The roots of
      human premolars were endodontically prepared and divided into 6 groups according
      to the combination of the main factors: adhesive (Ambar, FGM, Joinville, SC,
      Brazil; Adper Single Bond 2, 3MESPE, St Paul, MN; and XP Bond+self-cure
      activator, DeTrey Dentsply, Konstanz, Germany) and application mode (manual or
      sonic). The posts were cemented and the PBS tested at 0.5 mm/min. The NL was
      evaluated by scanning electron microscopy after the immersion of specimens in 50%
      silver nitrate. Micro-Raman spectroscopy was used to measure the in situ DC. Root
      third was also considered in the statistical evaluation. Data were analyzed by 3
      way repeated measures analysis of variance and Tukey tests (5%). RESULTS: Under
      sonic application, the PBS and the in situ DC increased, whereas NL decreased
      significantly for all groups in the middle and apical thirds (P < .05).
      CONCLUSIONS: The application of simplified adhesives by sonic mode in the root
      canal is a feasible tool to increase the fiber post bond to root canals.

PMID- 25069932
TI  - Effects of calcium silicate endodontic cements on biocompatibility and
      mineralization-inducing potentials in human dental pulp cells.
AB  - INTRODUCTION: The objective of this study was to evaluate the biocompatibility,
      inflammatory response, and odontoblastic potential of Biodentine (Septodont,
      Saint Maur des Fosses, France), Ortho-MTA (OMTA; BioMTA, Seoul, Korea), Angelus
      MTA (AMTA; Angelus, Londrina, Brazil), and IRM (Dentsply Tulsa Dental, Tulsa, OK)
      in human dental pulp cells. The underlying signaling mechanisms were also
      investigated. METHODS: Biocompatibilities were examined by the 3-(4,5
      dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Differentiation
      was assessed by alkaline phosphatase activity, alizarin red S staining, and
      reverse-transcription polymerase chain reaction for marker genes. The levels of
      inflammatory mediators and cytokines were measured by reverse-transcription
      polymerase chain reaction and enzyme-linked immunosorbent assay. Signal
      transduction analysis was performed by Western blotting. RESULTS: Biodentine,
      OMTA, and AMTA showed favorable cell proliferation, alkaline phosphatase
      activity, formation of mineralized nodules, and expression of odontoblastic
      marker genes that were similar to those of IRM. The levels of proinflammatory
      mediators including nitric oxide, prostaglandin E2, inducible nitric oxide
      synthase, and cyclooxygenase-2 were lower for Biodentine, OMTA, and AMTA compared
      with the IRM group. All test materials induced reactive oxygen species production
      and the expression of hemeoxygenase-1, nuclear factor-E2-related factor-2, and
      mitogen-activated protein kinases. CONCLUSIONS: These data indicate for the first
      time that the biocompatibility, inflammatory response, and odontoblastic
      differentiation of Biodentine were similar to that of OMTA and AMTA in HDPCs,
      which suggests that Biodentine could be good alternative pulp capping agent.

PMID- 25069934
TI  - Cone-beam computed tomographic scans in comparison with periapical radiographs
      for root canal length measurement: an in situ study.
AB  - INTRODUCTION: The primary aim of this study was to compare the precision of root
      canal length determination on cone-beam computed tomographic (CBCT) scans and
      periapical radiographs (PAs) with the actual root canal length. The secondary aim
      was to examine the influence of tooth type on root canal length measurements as
      assessed on CBCT scans and PAs. METHODS: In total, 40 root canals of 33 teeth
      (molars, premolars, canines, and incisors) out of 5 dentate maxillas of human
      cadavers were included. Root canal length measurement was performed by a
      consensus panel (2 examiners) on CBCT scans (3D Accuitomo 170; J Morita, Kyoto,
      Japan) and digital PAs. After straight-line access opening, a #15 file was
      fixated in every root canal at the length measured on CBCT scans. All teeth were
      extracted, and the root canal containing the file was uncovered. Measurements
      made on images taken with a digital camera (AxioCam; Carl Zeiss, Sliedrecht, The
      Netherlands) linked to a stereozoom microscope (Stemi SV6, Carl Zeiss) were used
      as the actual root canal length. RESULTS: When all roots were examined together,
      it was not clear which method is better for all types of teeth. For root canals
      of anterior teeth, there was no significant difference between the 2 methods. For
      root canals of posterior teeth, CBCT images gave results significantly closer to
      the actual root canal length in comparison with PAs (t value = -1.96; critical
      value is 1.74 with a significance level of 0.05). CONCLUSIONS: Root canal length
      measurements of posterior maxillary teeth were more accurate when assessed by
      CBCT images than PAs.

PMID- 25069936
TI  - Effects of 3 endodontic bioactive cements on osteogenic differentiation in
      mesenchymal stem cells.
AB  - INTRODUCTION: Because a root-end filling material comes into contact with the
      surrounding cells or tissues, understanding the cell-material interfacial
      activity is important. Thus, the purpose of this study was to assess the
      biocompatibility of 3 endodontic bioactive cements (MTA [Dentsply, Tulsa, OK],
      Bioaggregate [BA; Innovative Bioceramix, Vancouver, BC, Canada], and Biodentine
      [BD; Septodont, St Maur des Fosses, France]) and to investigate the effect of
      cements on the differentiation of mesenchymal stem cells. METHODS: Cell
      viability, mineralization, and differentiation were evaluated using an 2,3-bis(2
      methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium
      hydroxide (XTT) assay and alkaline phosphatase (ALP) staining. The expressions of
      ALP, osteocalcin, and bone sialoprotein at the gene level were detected by
      reverse-transcription polymerase chain reaction and real-time polymerase chain
      reaction. RESULTS: Cell viability of BD in concentrations of 1, 1/2, and 1/4 was
      significantly lower than MTA and BA (P < .05). There was no statistically
      significant difference in cell viability between materials in concentrations of
      1/10 and 1/50 (P < .05). The messenger RNA level of osteogenic genes increased
      significantly in the MTA and BA groups compared with controls (P < .05). However,
      although the messenger RNA level of osteogenic genes increased in the BD group,
      there was no statistically significant difference compared with controls. MTA,
      BA, and BD led to an increase in ALP staining compared with controls.
      CONCLUSIONS: In conclusion, MTA, BA, and BD have effects on osteoblast
      differentiation in mesenchymal stem cells, suggesting that these cements may be
      useful for root-end filling material.

PMID- 25069937
TI  - Micro-computed tomographic evaluation of canal transportation instrumented by
      different kinematics rotary nickel-titanium instruments.
AB  - INTRODUCTION: The purpose of this study was to evaluate and compare canal
      transportation of curved root canals by using 3 nickel-titanium systems:
      Reciproc, WaveOne, and Twisted Files Adaptive (TF). METHODS: Twenty-four
      extracted human mandibular molars with 2 separate mesial canals and severe angle
      of curvature were selected. Individual canals were divided randomly to 1 of the 3
      experimental groups: Reciproc group, reciprocating instrumentation with Reciproc
      R25; WaveOne group, reciprocating instrumentation with the Primary WaveOne file;
      and TF Adaptive group, Adaptive Rotary Motion with the TF files. Each group
      consisted of 16 root canals. Specimens were scanned before and after root canal
      preparation with an isotropic resolution of 20 MUm by using micro-computed
      tomography. The degree of canal transportation, in addition to instruments'
      centering ability, was recorded. RESULTS: Less transportation occurred with TF
      Adaptive rotary instruments (P < .0001). The mean degree of canal transportation
      in the apical third was significantly lower with TF Adaptive group (P < .0001).
      No significant difference was found between Reciproc and WaveOne systems (P =
      1.000). Mean centering ratio was the highest statistically with TF Adaptive (P <
      .0001), followed by WaveOne, and was minimal with Reciproc (P < .05).
      CONCLUSIONS: The TF Adaptive system was found to have less canal transportation
      and better centering ability when compared with the reciprocating groups.

PMID- 25069935
TI  - Effect of mineral trioxide aggregate surface treatments on morphology and bond
      strength to composite resin.
AB  - INTRODUCTION: The aim of this study was to evaluate the micromorphologic changes
      that accompany different surface treatments on mineral trioxide aggregate (MTA)
      and their effect on the bond strength to the composite resin with 4 adhesive
      systems. METHODS: Three types of MTA cement, ProRoot MTA (WMTA) (Dentsply, Tulsa,
      OK), MTA Angelus (AMTA) (Angelus, Londrina, PR, Brazil), and Endocem MTA (EMTA)
      (Maruchi, Wonju, Korea), were prepared and stored for a week to encourage
      setting. Surface treatment was performed using phosphoric acid or self-etch
      primer, and an untreated MTA surface was prepared as a control. The surface
      changes were observed using scanning electron microscopy. MTA surfaces were
      bonded with 4 adhesive systems, including Scotchbond Multipurpose (3M ESPE, St
      Paul, MN), Single Bond 2 (3M ESPE), Clearfil SE BOND (Kuraray, Osaka, Japan), and
      AdheSE One F (Ivoclar Vivadent, Schaan, Liechtenstein), to evaluate the adhesive
      effectiveness of MTA followed by composite resin restoration. The shear bond
      strength of the polymerized specimens was tested. RESULTS: For WMTA and AMTA,
      untreated surfaces showed an irregular crystalline plate with clusters of
      globular aggregate particles. For EMTA, the untreated surface presented a
      reticular matrix with acicular crystals. After surface treatment, superficial
      crystalline structures were eroded regardless of the MTA cement and adhesive
      system used. WMTA bonded significantly more strongly than AMTA and EMTA,
      regardless of the adhesive system used. In the WMTA and AMTA groups, AdheSE One F
      showed the highest bond strength to the composite. For EMTA, no significant
      differences were found across adhesive systems. CONCLUSIONS: Acidic treatment of
      the MTA surface affected the micromorphology and the bond strength to the
      composite. Within the limitations of this study, using a 1-step self-etch
      adhesive system might result in a strong bond to WMTA when the composite resin
      restoration is required over MTA cement.

PMID- 25069938
TI  - Cutting efficiency of Reciproc and waveOne reciprocating instruments.
AB  - INTRODUCTION: The aim of the present study was to evaluate the cutting efficiency
      of 2 new reciprocating instruments, Reciproc and WaveOne. METHODS: Twenty-four
      new Reciproc R25 and 24 new WaveOne Primary files were activated by using a
      torque-controlled motor (Silver Reciproc) and divided into 4 groups (n = 12):
      group 1, Reciproc activated by Reciproc ALL program; group 2, Reciproc activated
      by WaveOne ALL program; group 3, WaveOne activated by Reciproc ALL program; and
      group 4, WaveOne activated by WaveOne ALL program. The device used for the
      cutting test consisted of a main frame to which a mobile plastic support for the
      handpiece is connected and a stainless steel block containing a Plexiglas block
      (inPlexiglass, Rome, Italy) against which the cutting efficiency of the
      instruments was tested. The length of the block cut in 1 minute was measured in a
      computerized program with a precision of 0.1 mm. Means and standard deviations of
      each group were calculated, and data were statistically analyzed with 1-way
      analysis of variance and Bonferroni test (P < .05). RESULTS: Reciproc R25
      displayed greater cutting efficiency than WaveOne Primary for both the movements
      used (P < .05); in particular, Reciproc instruments used with their proper
      reciprocating motion presented a statistically significant higher cutting
      efficiency than WaveOne instruments used with their proper reciprocating motion
      (P < .05). There was no statistically significant difference between the 2
      movements for both instruments (P > .05). CONCLUSIONS: Reciproc instruments
      demonstrated statistically higher cutting efficiency than WaveOne instruments.

PMID- 25069939
TI  - Shaping ability of different nickel-titanium systems in simulated S-shaped canals
      with and without glide path.
AB  - INTRODUCTION: The objective of this study was to compare the shaping ability of
      different rotary and reciprocating nickel-titanium file systems with and without
      previous glide path preparation in simulated S-shaped canals. METHODS: One
      hundred twenty S-shaped canals in resin blocks were prepared to an apical size 25
      by using Reciproc, WaveOne, HyflexCM, F360, and OneShape systems either with or
      without previous glide path preparation (Pathfile) (12 canals/group). Material
      removal was measured at 20 measuring points, beginning 1 mm from the end point of
      preparation. Incidence of canal aberrations (zip/elbow, ledge formation),
      preparation time, and instrument failures were also recorded. Statistical
      analyses were performed by using analysis of variance and Tukey and chi(2) tests.
      RESULTS: For all systems, glide path preparation exerted no significant effect on
      preparation times (P > .05). Glide path preparation had no influence on the
      incidence of canal aberrations and instrument fractures (P > .05), with no
      significant differences between the 5 systems (P > .05). Glide path preparation
      had no influence on the centering ability of all systems (P > .05). On average,
      canals prepared with F360, OneShape, and HyflexCM remained better centered
      compared with those enlarged with WaveOne and Reciproc. CONCLUSIONS: Under the
      conditions of this study, glide path preparation had no significant impact on
      canal straightening. Less tapered instruments maintained the original canal
      curvature better than instruments having greater tapers.

PMID- 25069941
TI  - Accuracy and repeatability of 3 apex locators in locating root canal
      perforations: an ex vivo study.
AB  - INTRODUCTION: This study was an ex vivo evaluation of the accuracy and
      repeatability of 3 electronic apex locators (EALs) in locating simulated root
      canal perforations. METHODS: Thirty-five human teeth were used. Perforations were
      placed 5 mm from the apex of each specimen. A #15 K-file was attached to a
      micrometer, and the specimens were fixed in a mounting model. The EALs were
      connected to the files, and electronic measurements of the simulated perforations
      were obtained. This procedure was repeated, the files were cemented in place, and
      x-rays were obtained to evaluate the distances between the measurement files and
      the simulated perforations. The obtained results were compared with the
      corresponding control lengths. Three investigators evaluated the distance of the
      file position in relation to the perforation for each specimen. The 3
      investigators reached consensus regarding these measurements. RESULTS:
      Statistical analyses of the results revealed that the EAL reliabilities in the
      exact detections of the root canal perforations were 97.1% for the Mini Apex
      Locator, 100% for the Root SW, and 91.4% for the Root ZX II. Analysis of variance
      revealed that the accuracies of the 3 devices were not different (P > .05). The
      results also indicated high levels of repeatability for each of the 3 EALs
      (intraclass correlation coefficients: 0998, 0.999, and 0.999 for the Mini Apex
      Locator, Root SW, and Root ZX II, respectively). CONCLUSIONS: It was concluded
      that each of these 3 EALs provided excellent ex vivo accuracy in locating root
      perforations and that all tested devices possess excellent ex vivo repeatability.

PMID- 25069940
TI  - Assessment of color stability of white mineral trioxide aggregate angelus and
      bismuth oxide in contact with tooth structure.
AB  - INTRODUCTION: Dental discoloration with use of materials containing bismuth oxide
      has been reported. It is postulated that the discoloration is a result of
      chemical interaction of bismuth oxide with dentin. The aim of the study was to
      analyze dental color alteration and the chemical interaction of bismuth oxide
      with the main components present in composite (methacrylate) and in dentin
      (collagen). METHODS: Fifty bovine teeth were prepared and filled with white
      mineral trioxide aggregate (MTA) Angelus, Portland cement (PC) with 20% zirconium
      oxide, or PC with 20% calcium tungstate and then sealed with composite. Triple
      antibiotic paste and unfilled samples were the positive and negative controls,
      respectively. The specimens were stored in separate flasks immersed in tap water
      at 37 degrees C with ambient light blocked out. The color assessment was
      performed with a spectrophotometer at different intervals, namely before filling
      and 24 hours, 15 days, and 30 days after filling. The color change and the
      luminosity were calculated. The statistical analysis was performed by using
      nonparametric Kruskal-Wallis and Dunn tests (P < .05). The interaction of the
      bismuth oxide, zirconium oxide, and calcium tungstate with collagen and
      methacrylate was assessed by placing the materials in contact, followed by color
      assessment. RESULTS: The analysis of color change values showed that all the
      materials presented color alteration after the evaluated periods. Statistically
      higher luminosity was verified for PC/20% zirconium oxide in comparison with
      white MTA Angelus (P < .05). The teeth filled with white MTA Angelus demonstrated
      a grayish discoloration with evident dentin staining. Bismuth oxide exhibited a
      color change when in contact with collagen. CONCLUSIONS: The color of white MTA
      Angelus was altered in contact with dental structures. Collagen, which is present
      in dentin matrix, reacted with bismuth oxide, resulting in a grayish
      discoloration. The use of an alternative radiopacifier to replace bismuth in
      white MTA is indicated.

PMID- 25069942
TI  - Cyclic fatigue resistance of nickel-titanium instruments after immersion in
      irrigant solutions with or without surfactants.
AB  - INTRODUCTION: The aim of the study was to assess cyclic fatigue resistance of
      reciprocating (Reciproc and WaveOne) and continuous rotating (ProTaper) nickel
      titanium files after immersion in different irrigation solutions with or without
      surfactants during several short time periods. METHODS: A total of 270 new
      Reciproc R25, WaveOne Primary, and ProTaper F2 files were tested. Instruments of
      each brand were divided into 1 control group (n = 10) formed by new files and 4
      test groups (n = 20) formed by instruments dynamically immersed at 37 degrees C
      for 16 mm in 5.25% sodium hypochlorite (NaOCl), Hypoclean (5.25% NaOCl with
      surfactant), 17% EDTA, or EDTA Plus (17% EDTA with surfactant). Each test group
      was subdivided into 2 subgroups (n = 10) on the basis of the time of dynamic
      immersion in the endodontic irrigant solution (45 seconds or 3 minutes).
      Resistance to cyclic fatigue was determined by recording time to fracture in a
      stainless steel artificial canal with a 60 degrees  angle of curvature and 5-mm
      radius of curvature. The fracture surface was examined by using scanning electron
      microscopy. RESULTS: Immersion in NaOCl did not reduce the cyclic fatigue of
      reciprocating or continuous nickel-titanium files. The 17% EDTA reduced the
      fatigue resistance of all instruments after 3 minutes. The immersion in irrigants
      with surfactants did not influence the cyclic fatigue of instruments except for
      Reciproc immersed in Hypoclean solution. CONCLUSIONS: EDTA immersion reduced the
      cyclic fatigue resistance of all instruments after 3 minutes. Addition of
      surfactants did not influence the cyclic fatigue of files except when added to
      NaOCl when it contacts Reciproc instruments.

PMID- 25069943
TI  - Mineral trioxide aggregate as apical plug in teeth with necrotic pulp and
      immature apices: a 10-year case series.
AB  - INTRODUCTION: This 10-year study evaluated the clinical and radiologic outcomes
      of teeth with necrotic pulp, immature apices, and periapical lesions treated with
      the mineral trioxide aggregate (MTA) apical plug technique. METHODS: Seventeen
      single-rooted immature teeth with necrotic pulp and periapical lesion from 17
      patients treated between January 2001 and December 2001 were included in this
      study. Apical obturation on all teeth included in the study was completed in 2
      visits: first using calcium hydroxide as an interappointment intracanal
      medication and a second visit for the creation of the artificial apical barrier
      with MTA. The outcome, based on clinical and radiographic criteria, was assessed
      by 2 calibrated investigators using the periapical index (PAI). The Friedman test
      was used to verify the differences between baseline and the 1-, 5-, and 10-year
      PAI scores. RESULTS: Of the 17 patients treated, 1 patient dropped out at 5
      years. At the 10-year follow-up, 15 teeth were healed (PAI <=2), and 1 tooth had
      been extracted because of the presence of a longitudinal root fracture. The PAI
      score exhibited a significant decrease between baseline and 1 year and between 1
      and 5 years. The difference between 5 and 10 years was not significant.
      CONCLUSIONS: The apical plug with MTA was a successful and effective technique
      for long-term management of this group of teeth with necrotic pulps with immature
      root development and periapical lesions.

PMID- 25069944
TI  - Management of longstanding furcation perforation using a novel approach.
AB  - INTRODUCTION: Iatrogenic furcation perforation may occur during the access
      preparation of the endodontic treatment. This may lead to periodontal defects and
      subsequent tooth loss. In this case report, we presented a new approach that may
      help salvage cases with a longstanding furcation involvement and substantial bone
      loss resulting from perforation. METHODS: A mandibular molar case that had a
      furcation perforation and longstanding furcation bone loss with a probing depth
      of 10 mm in the buccal furcation area. We applied a novel approach, which used
      both nonsurgical and surgical interventions. We first reaccessed the tooth to
      reseal the perforation site with MTA followed by a newly designed surgical
      approach including the use of a stent, a reverse submarginal flap, Emdogain
      (Straumann USA, Andover, MA), guided bone regeneration, and postoperative
      isolation of the surgical site. The post-treatment follow-ups with up to 19-month
      recall showed favorable results with significant bone regeneration at the
      furcation and the probing depth reduced to 4-5 mm. CONCLUSIONS: Longstanding
      furcation perforations with periodontal involvement may be savable and have a
      better prognosis. This may require a modified flap design to access the defect,
      guided bone and periodontal regeneration, and postoperative isolation of the
      surgical defect.

PMID- 25069945
TI  - Root resorption caused by jaw infiltration of multiple myeloma: report of a case
      and literature review.
AB  - INTRODUCTION: Infiltration of the maxillofacial region by multiple myeloma is
      common and typically appears as punched out osteolytic lesions of the jaws.
      Although swelling, bone pain, and tooth mobility are characteristic clinical
      symptoms, root resorption is rare in conjunction with myeloma nests. METHODS: A
      case of a 67-year-old man with multiple myeloma is presented. Root resorption of
      the second mandibular premolar and the first and second molars on the right side,
      with consecutive tooth mobility, was the initial manifestation of the disease and
      was primarily detected on a periapical radiograph. The treating dentist referred
      the patient to the department for further examination, which revealed multiple
      myeloma. The patient received tandem high-dose chemotherapy and autologous stem
      cell transplantation as standard myeloma treatment. Intravenous bisphosphonates
      were administered to curb the osteolytic lesions. RESULTS: No signs of
      bisphosphonate-related osteonecrosis of the jaw were observed until the end of
      the follow-up period. CONCLUSIONS: Only 5 reports of myeloma-associated root
      resorption have been reported in the literature. In all cases, mandibular
      premolars or molars were involved, and the patients exhibited extensive
      involvement of the jaw by myeloma. This report highlights the importance of
      correct interpretation of clinical signs and radiographs by dental specialists in
      the diagnostic algorithm of systemic diseases. Furthermore, this is an example
      for the inevitable part of bisphosphonates in the treatment of osteolytic
      processes.

PMID- 25069946
TI  - Transient apical breakdown and its relationship with orthodontic forces: a case
      report.
AB  - INTRODUCTION: Transient apical breakdown (TAB) caused by orthodontic treatment is
      a reversible resorptive process in which the apex of a tooth shows some
      radiographic evidence of resorption and the crown may display some discoloration.
      It usually requires no treatment other than monitoring and elimination of the
      orthodontic forces applied to the tooth. METHODS: This report describes the case
      of a 48-year-old man patient who was referred to the department of endodontics
      for evaluation of some discoloration of his upper right central incisor, which
      was undergoing orthodontic treatment. The tooth was nonresponsive to sensitivity
      tests, it was sensitive to percussion, and, radiographically, there was some
      evidence of root resorption and apical radiolucency. RESULTS: Because TAB was the
      suspected cause of the signs and symptoms, no treatment was performed on the
      tooth except for periodic recalls, and lightening and eventual removal of the
      orthodontic appliances was indicated. CONCLUSIONS: Ten weeks after the initial
      appointment and removal of the applied orthodontic forces, color improvement was
      observed, accompanied by a return of tooth sensitivity to cold tests.

PMID- 25069947
TI  - Repair of extensive apical root resorption associated with apical periodontitis:
      radiographic and histologic observations after 25 years.
AB  - INTRODUCTION: Root resorption is a frequent finding in teeth with apical
      periodontitis. In cases of severe apical periodontitis, root resorption may
      involve not only cementum but also dentin. Resorbed tooth structures can only be
      repaired with cementum because stem cells in the periradicular tissues are not
      capable of differentiating into odontoblasts. This article reports the repair of
      extensive apical root resorption associated with apical periodontitis 25 years
      after treatment. METHODS: A 51-year-old man presented with pulp necrosis and
      symptomatic apical periodontitis in tooth #7. The periapical radiograph showed a
      large radiolucent periradicular lesion and severe root resorption. Nonsurgical
      root canal therapy was performed. Twenty-five years after treatment, a crown
      fracture developed, and the tooth could not be restored. The periapical
      radiograph revealed complete healing of the previous apical periodontitis lesion
      and restoration of the resorbed root structure. The tooth was removed and
      examined histologically. RESULTS: The apical canal was almost completely filled
      with a cementumlike tissue with some strands of entrapped vital uninflamed
      connective tissue. Areas of cementum and dentin resorption in the apical third
      were repaired by a combination of cellular and acellular cementum to which
      periodontal ligament fibers were attached. CONCLUSIONS: Root resorption caused by
      apical periodontitis can be restored almost to its normal structure after
      adequate nonsurgical root canal treatment that succeeded in controlling
      infection. The mechanisms behind this process are not clear but probably involve
      signaling pathways regulating root development, cell-cell and cell-matrix
      interaction, and morphogens.

PMID- 25069948
TI  - Sodium hypochlorite chemical burn in an endodontist's eye during canal treatment
      using operating microscope.
AB  - INTRODUCTION: This study describes a case of eye burn induced by sodium
      hypochlorite used as an irrigant during root canal preparation. METHODS: A 24
      year-old female endodontist was using an operating microscope during root canal
      treatment, and as the root canal was irrigated, the pressure cannula burst and
      the irrigant (3.5% sodium hypochlorite) came into direct contact with her left
      eye. She immediately sought ophthalmologic emergency care for pain, redness of
      the cornea, burning sensation, photophobia, intraocular pressure, and blurred
      vision. The initial treatment consisted of washing the eye with saline solution
      and administering analgesic and anti-inflammatory (steroid) medications. One day
      after the accident, a topical demulcent and hydroxypropyl medication were applied
      to the eyeball (conjunctiva), the eye was bandaged for 24 hours, and rest was
      prescribed for 7 days. Eight days later, a corneal ulcer was diagnosed, and
      antibiotic and anti-inflammatory (steroid) medications were used. RESULTS: Vision
      was restored without any sequelae 4 weeks after the accident. The endodontist was
      instructed to apply control medication (Lagricel; Sophia SA, Caracas, Venezuela)
      for 3 months and to return for ophthalmologic follow-up every 6 months.
      CONCLUSIONS: Sodium hypochlorite is an effective antibacterial irrigant indicated
      for the treatment of root canal infections. The tissue cytotoxicity highlights
      the need to inform the patient of the risk factors of accidents and enhance care
      with individual protection equipment for the patient and the professional during
      clinical procedures.

PMID- 25069949
TI  - How do changes to the built environment influence walking behaviors? A
      longitudinal study within a university campus in Hong Kong.
AB  - BACKGROUND: Previous studies testing the association between the built
      environment and walking behavior have been largely cross-sectional and have
      yielded mixed results. This study reports on a natural experiment in which
      changes to the built environment were implemented at a university campus in Hong
      Kong. Longitudinal data on walking behaviors were collected using surveys, one
      before and one after changes to the built environment, to test the influence of
      changes to the built environment on walking behavior. METHODS: Built environment
      data are from a university campus in Hong Kong, and include land use, campus bus
      services, pedestrian network, and population density data collected from campus
      maps, the university developmental office, and field surveys. Walking behavior
      data were collected at baseline in March 2012 (n = 198) and after changes to the
      built environment from the same cohort of subjects in December 2012 (n = 169)
      using a walking diary. Geographic information systems (GIS) was used to map
      walking routes and built environment variables, and compare each subject's
      walking behaviors and built environment exposure before and after the changes to
      the built environment. Walking behavior outcomes were changes in: i) walking
      distance, ii) destination-oriented walking, and iii) walked altitude range.
      Multivariable linear regression models were used to test for associations between
      changes to the built environment and changes in walking behaviors. RESULTS:
      Greater pedestrian network connectivity predicted longer walking distances and an
      increased likelihood of walking as a means of transportation. The increased use
      of recreational (vs. work) buildings, largely located at mid-range altitudes, as
      well as increased population density predicted greater walking distances.Having
      more bus services and a greater population density encouraged people to increase
      their walked altitude range. CONCLUSIONS: In this longitudinal study, changes to
      the built environment were associated with changes in walking behaviors. Use of
      GIS combined with walking diaries presents a practical method for mapping and
      measuring changes in the built environment and walking behaviors, respectively.
      Additional longitudinal studies can help clarify the relationships between the
      built environment and walking behaviors identified in this natural experiment.

PMID- 25069950
TI  - Transmission route and genotype of chronic hepatitis B virus infection in
      children in Japan between 1976 and 2010: A retrospective, multicenter study.
AB  - AIM: The aim of this study was to clarify the trends of the infectious source of
      chronic hepatitis B virus (HBV) infection and the HBV genotype in the Japanese
      pediatric population over the last three decades. METHODS: The present study was
      a retrospective, nationwide, multicenter study. Patients who were under 20 years
      of age when diagnosed with chronic HBV infection were eligible for enrollment in
      this study. A total of 430 patients (male/female, 256/174; age at the time of
      writing, 1-37 years; median age, 14 years; birth year, 1976-2010) from 11
      hospitals were evaluated. RESULTS: The incidence of chronic HBV infection from
      1976 to 1980, 1981-1985, 1986-1990, 1991-1995, 1996-2000, 2001-2005 and 2006-2010
      was 56, 52, 34, 37, 81, 92 and 78, respectively. Of the 430 patients, 304 (71%),
      61 (14%), 11 (3%) and 54 (13%) were infected via mother-to-child transmission,
      close contact, blood transfusion and unknown source, respectively. After the
      introduction of perinatal immunoprophylaxis, the rate of mother-to-child
      transmission increased from 62% during the 1991-1995 period to 86% during the
      2006-2010 period. The distributions of genotypes A, B, C, D and F were 3%, 9%,
      86%, 2% and 1%, respectively. No obvious change was observed in the distribution
      of genotypes. Genotype C was significantly associated with mother-to-child
      transmission. CONCLUSION: Mother-to-child transmission remains the primary source
      of chronic HBV infection after the introduction of immunoprophylaxis. Taking
      measures to prevent immunoprophylaxis failure is essential to reduce pediatric
      chronic HBV infection in Japan.

PMID- 25069951
TI  - A QM/MM MD study of the pH-dependent ring-opening catalysis and lid motif
      flexibility in glucosamine 6-phosphate deaminase.
AB  - The glucosamine 6-phosphate deaminase (NagB), which catalyzes the conversion of D
      glucosamine 6-phosphate (GlcN6P) into d-fructose 6-phosphate (F6P) and ammonia,
      determines the final metabolic fate of N-acetylglucosamine (GlcNAc). Here using
      state-of-the-art ab initio QM/MM MD simulations, we have explored the plausible
      mechanisms for the enzymatic ring-opening of GlcN6P in the basic environment. Two
      different proton-shuttle mechanisms have been proposed. Calculations show that
      the protonated state of the amino group in the substrate dominates the concerted
      and stepwise catalytic pathways and a catalytic triad plays an important role in
      mediating the proton transfer and the resulting ring-opening process. The free
      energy barrier for the rate-determining step in the low-energy stepwise reaction
      is 17.9 kcal mol(-1). In acidic solution, the lid motif prefers a closed state
      while it always stays in the open state in basic solution upon substrate binding,
      which is basically dominated by the protonated state of the residue His145.

PMID- 25069952
TI  - Early mobilization on continuous renal replacement therapy is safe and may
      improve filter life.
AB  - INTRODUCTION: Despite studies demonstrating benefit, patients with femoral
      vascular catheters placed for continuous renal replacement therapy are frequently
      restricted from mobilization. No researchers have reported filter pressures
      during mobilization, and it is unknown whether mobilization is safe or affects
      filter lifespan. Our objective in this study was to test the safety and
      feasibility of mobilization in this population. METHODS: A total of 33 patients
      undergoing continuous renal replacement therapy via femoral, subclavian or
      internal jugular vascular access catheters at two general medical-surgical
      intensive care units in Australia were enrolled. Patients underwent one of three
      levels of mobilization intervention as appropriate: (1) passive bed exercises,
      (2) sitting on the bed edge or (3) standing and/or marching. Catheter
      dislodgement, haematoma and bleeding during and following interventions were
      evaluated. Filter pressure parameters and lifespan (hours), nursing workload and
      concern were also measured. RESULTS: No episodes of filter occlusion or failure
      occurred during any of the interventions. No adverse events were detected. The
      intervention filters lasted longer than the nonintervention filters (regression
      coefficient = 13.8 (robust 95% confidence interval (CI) = 5.0 to 22.6), P =
      0.003). In sensitivity analyses, we found that filter life was longer in patients
      who had more position changes (regression coefficient = 2.0 (robust 95% CI = 0.6
      to 3.5), P = 0.007). The nursing workloads between the intervention shift and the
      following shift were similar. CONCLUSIONS: Mobilization during renal replacement
      therapy via a vascular catheter in patients who are critically ill is safe and
      may increase filter life. These findings have significant implications for the
      current mobility restrictions imposed on patients with femoral vascular catheters
      for renal replacement therapy. TRIAL REGISTRATION: Australian and New Zealand
      Clinical Trials Registry ACTRN12611000733976 (registered 13 July 2011).

PMID- 25069953
TI  - Evolutionary acquisition of cysteines determines FOXO paralog-specific redox
      signaling.
AB  - Reduction-oxidation (redox) signaling, the translation of an oxidative
      intracellular environment into a cellular response, is mediated by the reversible
      oxidation of specific cysteine thiols. The latter can result in disulfide
      formation between protein hetero- or homodimers that alter protein function until
      the local cellular redox environment has returned to the basal state. We have
      previously shown that this mechanism promotes the nuclear localization and
      activity of the Forkhead Box O4 (FOXO4) transcription factor. AIMS: In this
      study, we sought to investigate whether redox signaling differentially controls
      the human FOXO3 and FOXO4 paralogs. RESULTS: We present evidence that FOXO3 and
      FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution.
      Using a proteome-wide screen, we identified previously unknown redox-dependent
      FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and
      Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is
      required for its reactive oxygen species-induced nuclear translocation. FOXO4
      does not interact with IPO7 or IPO8. INNOVATION AND CONCLUSION: IPO7 and IPO8
      control the nuclear import of FOXO3, but not FOXO4, in a redox-sensitive and
      disulfide-dependent manner. Our findings suggest that evolutionary acquisition of
      cysteines has contributed to regulatory divergence of FOXO paralogs, and that
      phylogenetic analysis can aid in the identification of cysteines involved in
      redox signaling.

PMID- 25069955
TI  - Nitrogen and sulfur codoped graphene: multifunctional electrode materials for
      high-performance li-ion batteries and oxygen reduction reaction.
AB  - N and S codoping of graphene is realized by a novel approach: covalent
      functionalization of graphene oxide using 2-aminothiophenol as a source of both N
      and S followed by thermal treatment. The resulting N- and S-codoped graphene has
      potential applications in high-performance lithium-ion batteries and as a metal
      free catalyst for oxygen reduction reaction. 

PMID- 25069954
TI  - Cannabinoid findings in children hair - what do they really tell us? An
      assessment in the light of three different analytical methods with focus on
      interpretation of Delta9-tetrahydrocannabinolic acid A concentrations.
AB  - Hair analysis for drugs and drugs of abuse is increasingly applied in child
      protection cases. To determine the potential risk to a child living in a
      household where drugs are consumed, not only can the hair of the parents be
      analyzed but also the hair of the child. In the case of hair analysis for
      cannabinoids, the differentiation between external contamination and systemic
      uptake is particularly difficult, since the drug is quite often handled
      extensively prior to consumption (e.g. when preparing a joint) and smoke causes a
      further risk for an external contamination. Delta9-tetrahydrocannabinolic acid A
      (THCA-A), the non-psychoactive biogenetic precursor of Delta9
      tetrahydrocannabinol (THC), is a suitable marker for external contamination since
      it is not incorporated into the hair matrix through the bloodstream in relevant
      amounts. In the presented study, hair samples from 41 children, 4 teenagers, and
      34 drug-consuming parents were analyzed for THCA-A, THC and cannabinol (CBN)
      applying methanolic extraction and a fully validated liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method (Method 1). For comparison, a part of the
      samples was also analyzed applying alkaline hydrolysis followed by liquid/liquid
      extraction and gas chromatography-mass spectrometry (GC-M)S (Method 2), or by
      headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS
      SPME-GC-MS) (Method 3). Furthermore, 458 seized marihuana samples and 180 seized
      hashish samples were analyzed for the same cannabinoids by gas-chromatography
      flame ionization detector (GC-FID). In all but one of the hair samples, the
      concentration of THCA-A was higher than the concentration of THC and in 14 cases
      no THC could be detected despite the presence of THCA-A, suggesting that in
      almost all cases a significant external contamination had occurred. Within-family
      comparison showed a higher THCA-A/THC ratio in hair of children than of their
      consuming caregivers. Mean and median of this ratio of all hair samples (6.7 and
      4.2) were between those of marihuana (11.0 and 8.3) and hashish (2.8 and 2.1)
      with a large variation in all samples. Comparison of the Methods 1 to 3 showed
      clearly that the choice of the analytical procedure has a strong influence on the
      quantitative results, mainly because of decarboxylation of THCA-A during hair
      hydrolysis by NaOH and other analytical steps, which lead to artifactually
      elevated THC concentrations. In conclusion, these findings suggest that the major
      part of the cannabinoids detected in the hair samples from children arose from an
      external contamination through 'passive' transfer by e.g. contaminated hands or
      surfaces and not from inhalation or deposition of side stream smoke.

PMID- 25069956
TI  - Outpatient Psychiatric Documentation Use by Primary Care Physicians Following De
      Sensitization in the Electronic Medical Record.
AB  - OBJECTIVE: The authors assessed the ways in which primary care physicians (PCPs)
      utilize outpatient psychiatric documentation that has recently become accessible
      to non-psychiatric providers in the UC Davis Healthcare System electronic medical
      record (EMR). METHODS: The authors distributed a nine-question paper survey to 71
      PCPs on the UC Davis Medical Center Campus in Sacramento, California. Questions
      addressed awareness of changes in accessibility of psychiatric documentation,
      which parts of the psychiatric note were most useful, and ways in which reviewing
      psychiatric notes changed providers' practice and perception of patients with
      mental illness. RESULTS: Survey return rate was 100 % due to in-person
      distribution and collection of survey. More than half (58 %) of respondents were
      unaware that they had access to psychiatric notes. Within the psychiatric note,
      providers focused most on plan, diagnosis, and assessment components. Those who
      were aware reported improved understanding (97 %) and comfort with discussing
      mental illness (79 %), increased consideration of side effects of psychiatric
      medications (79 %), and improved efficiency in encounters with psychiatric
      patients (97 %). Responses about likelihood to contact psychiatrists directly
      varied considerably. About 45 % of respondents were more likely to consider
      psychosomatic etiology for patients who were also seen by outpatient psychiatry.
      CONCLUSIONS: Overall, PCPs reported that accessibility of outpatient psychiatric
      notes significantly enhanced their experience of caring for patients with mental
      illness. Future goals include increasing awareness and education about
      availability of psychiatric notes as well as optimizing communication between
      psychiatrists and PCPs. The authors recommend future studies focused on changes
      in perceptions among providers as a result of continued use of psychiatric
      documentation.

PMID- 25069957
TI  - Inferring the perturbed microRNA regulatory networks from gene expression data
      using a network propagation based method.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of endogenous small regulatory RNAs.
      Identifications of the dys-regulated or perturbed miRNAs and their key target
      genes are important for understanding the regulatory networks associated with the
      studied cellular processes. Several computational methods have been developed to
      infer the perturbed miRNA regulatory networks by integrating genome-wide gene
      expression data and sequence-based miRNA-target predictions. However, most of
      them only use the expression information of the miRNA direct targets, rarely
      considering the secondary effects of miRNA perturbation on the global gene
      regulatory networks. RESULTS: We proposed a network propagation based method to
      infer the perturbed miRNAs and their key target genes by integrating gene
      expressions and global gene regulatory network information. The method used
      random walk with restart in gene regulatory networks to model the network effects
      of the miRNA perturbation. Then, it evaluated the significance of the correlation
      between the network effects of the miRNA perturbation and the gene differential
      expression levels with a forward searching strategy. Results show that our method
      outperformed several compared methods in rediscovering the experimentally
      perturbed miRNAs in cancer cell lines. Then, we applied it on a gene expression
      dataset of colorectal cancer clinical patient samples and inferred the perturbed
      miRNA regulatory networks of colorectal cancer, including several known oncogenic
      or tumor-suppressive miRNAs, such as miR-17, miR-26 and miR-145. CONCLUSIONS: Our
      network propagation based method takes advantage of the network effect of the
      miRNA perturbation on its target genes. It is a useful approach to infer the
      perturbed miRNAs and their key target genes associated with the studied
      biological processes using gene expression data.

PMID- 25069959
TI  - Long-term clinical and angiographic outcomes after sirolimus- and paclitaxel
      eluting stent placement following rotablation for severely calcified lesions: a
      retrospective nonrandomized study.
AB  - We conducted a retrospective comparison of the long-term clinical and
      angiographic outcomes of 281 consecutive nonrandomized severely calcified lesions
      in 221 patients treated with a sirolimus-eluting stent (SES; CYPHER Bx VELOCITY)
      or a paclitaxel-eluting stent (PES; TAXUS Express) placed after rotablation
      between August 2004 and February 2009. The clinical safety endpoint, comprising
      the incidence of cardiac death, nonfatal recurrent myocardial infarction, and
      definite stent thrombosis, in 164 patients after exclusive SES placement (4.9 %
      with a mean clinical follow-up period of 1396 +/- 763 days) was not significantly
      different from that after exclusive PES placement in 51 patients (2.0 %, 1011 +/-
      605 days; p = 0.364 and p < 0.001, respectively). The cumulative clinical safety
      endpoint-free ratio after exclusive SES placement was not significantly different
      from that after PES placement (p = 0.61, by log-rank test). The angiographic
      efficacy endpoint (binary restenosis: diameter stenosis >50 % at follow-up
      angiography) in the 169 lesions placed using SES (20.1 % with a mean angiographic
      follow-up period of 669 +/- 605 days) was not significantly different from that
      in the 40 lesions using PES (17.5 %; 498 +/- 320 days) (p = 0.707). In univariate
      analysis, SES use did not relate to the efficacy endpoint (p = 0.707). Thus, our
      small single-center study showed that the long-term clinical and angiographic
      outcomes after SES placements for severely calcified lesions after rotablation
      were not significantly different from those after PES placement.

PMID- 25069958
TI  - Global genetic architecture of an erythroid quantitative trait locus, HMIP-2.
AB  - HMIP-2 is a human quantitative trait locus affecting peripheral numbers, size and
      hemoglobin composition of red blood cells, with a marked effect on the
      persistence of the fetal form of hemoglobin, HbF, in adults. The locus consists
      of multiple common variants in an enhancer region for MYB (chr 6q23.3), which
      encodes the hematopoietic transcription factor cMYB. Studying a European
      population cohort and four African-descended groups of patients with sickle cell
      anemia, we found that all share a set of two spatially separate HbF-promoting
      alleles at HMIP-2, termed "A" and "B." These typically occurred together ("A-B")
      on European chromosomes, but existed on separate homologous chromosomes in
      Africans. Using haplotype signatures for "A" and "B," we interrogated public
      population datasets. Haplotypes carrying only "A" or "B" were typical for
      populations in Sub-Saharan Africa. The "A-B" combination was frequent in
      European, Asian, and Amerindian populations. Both alleles were infrequent in
      tropical regions, possibly undergoing negative selection by geographical factors,
      as has been reported for malaria with other hematological traits. We propose that
      the ascertainment of worldwide distribution patterns for common, HbF-promoting
      alleles can aid their further genetic characterization, including the
      investigation of gene-environment interaction during human migration and
      adaptation. 

PMID- 25069960
TI  - Balloon valvuloplasty in rheumatic aortic valve stenosis: immediate and long-term
      results.
AB  - To study the immediate and long-term results of balloon aortic valvuloplasty
      (BAV) in a large cohort of patients with rheumatic valvular aortic stenosis.
      Single tertiary care center retrospective data analysis of immediate and long
      term outcomes in patients following BAV from 2000 to 2008. Ninety-two patients
      with rheumatic aortic stenosis (AS) were studied who underwent BAV. Mean age of
      patients was 21.7 years (95 % CI 14.3-28.9) with mean follow-up period of 5.7
      years (+/-SD 1.3). Intervention resulted in successful BAV (more than 50 %
      reduction in baseline gradient) in 79 (85.9 %) subjects (Group A) and partially
      successful BPV (<50 % reduction in baseline gradient) in 8 (8.7 %) subjects
      (Group B). BAV failed in 5 (5.4 %) subjects (Group C). Concomitant balloon mitral
      valvuloplasty was done in 23/92 cases. Mean left ventricular systolic pressure
      decreased from 165.6 (95 % CI 142.7-196.3) to 110.9 mmHg (95 % CI 92.1-129.6), (P
      < 0.001) and mean aortic valve (AV) gradient from 50.7 (95 % CI 35.12-66.22) to
      27.2 mmHg (95 % CI 25.83-31.23), (P < 0.001). The mean change in ejection
      fraction and mean AV gradient were significantly different between success
      (Groups A and B) and failure groups (P < 0.001). Different grades of aortic
      regurgitation were noted in 32 (34.78 %) patients post BAV (severe regurgitation
      in 2.18 %). Anova post hoc analysis showed sustained gradient reductions at 1-
      and 5-year follow-up (P > 0.05). The need for surgery was much lower in Group A
      (2.5 %) compared to Group B (50 %) and C (100 %). BAV is an effective treatment
      strategy in dominant AS in multi valvular rheumatic disease situations. Combined
      aortic and mitral valvuloplasty was performed in one-fourth of study patients.

PMID- 25069961
TI  - Relationship between core strength and key variables of performance in elite rink
      hockey players.
AB  - AIM: The aim of this study was to test the hypothesis that a significant
      relationship exists between the level of core strength-endurance and key
      variables of endurance, strength, power, speed, and agility performance in male
      elite rink hockey players. METHODS: Ten male elite rink hockey players of the
      German national team were tested for 1) time to exhaustion, maximum oxygen
      uptake, and running economy, 2) one repetition maximum bench press and half
      squat, 3) counter movement jump height, 4) 5 m, 10 m, and 20 m speed, and 5) 22 m
      agility. The rink hockey players were also tested for 6) ventral, lateral-left,
      lateral-right, and dorsal core strength-endurance using concentric-eccentric
      muscle tests. RESULTS: The level of total and ventral core strength-endurance was
      very largely correlated with maximum oxygen uptake (r=0.74 and r=0.71, both
      P<0.05). Additionally, there was a large correlation between the level of ventral
      core strength-endurance and time to exhaustion (r=0.66, P<0.05). No further
      significant relationships were observed (best r=0.60, P>0.05). CONCLUSION: The
      findings from this study suggest that the level of core strength-endurance is
      largely to very largely correlated with key variables of endurance performance,
      but not significantly with strength, power, speed, or agility indicators in male
      elite rink hockey players. These findings should be noted by coaches and
      scientists when testing physical fitness or planning strength and conditioning
      programs for male elite rink hockey players.

PMID- 25069962
TI  - Oxidative stress in blood of healthy people after diving.
AB  - AIM: The aim of this study was to investigate the effect of diving on the level
      of lipid peroxidation products and the activity of antioxidant enzyme in blood of
      healthy volunteers. METHODS: The studied group consisted of 11 experienced
      divers, who spent 40 min submerged in water, at an average depth of 6.2 m with
      water temperature of 13oC. Blood samples were taken before diving and immediately
      after surfacing. The concentration of conjugated dienes (CD) and thiobarbituric
      acid reactive substances (TBARS) was assayed both in blood plasma and
      erythrocytes, while the activity of superoxide dismutase (SOD) in erythrocytes.
      RESULTS: A statistically significant increase of CD level in blood plasma and an
      increasing tendency in erythrocytes with concomitant decrease of SOD activity was
      observed after diving. No statistically significant changes in concentration of
      TBARS both in blood plasma and erythrocytes were revealed. CONCLUSION: The
      changes in environmental conditions during diving cause the oxidant-antioxidant
      imbalance, as it is evidenced by observed increase of CD level, which are the
      primary markers of lipid peroxidation and the decrease of SOD activity. No
      changes in the level of secondary products of lipid peroxidation - TBARS, may
      suggest that in studied subjects inhibition of free-radical processes occurs
      and/or the products of lipid peroxidation are quickly removed due to adaptation,
      what protect the divers against damages on cellular level.

PMID- 25069963
TI  - Metabolic and ventilatory thresholds assessment in front crawl swimming.
AB  - AIM: The purpose of this study was to assess and characterize the ventilatory
      anaerobic threshold in swimming, and to verify if the anaerobic metabolic
      threshold could be accurately estimated using ventilatory parameters. METHODS:
      Twenty-eight national-level male swimmers performed a n x 200 m front crawl
      individualized intermittent incremental protocol, with 30 s rest intervals, until
      exhaustion. The ventilatory variables and heart rate were continuously measured
      using a telemetric portable gas analyser. The capillary blood samples for lactate
      concentration analysis were collected from the earlobe at rest, during rest
      intervals, and at the end of exercise. RESULTS: No significant differences were
      observed between the ventilatory and metabolic thresholds for lactate
      concentration, heart rate and velocity (P=0.62, 0.80 and 0.78, respectively). The
      Bland-Altman plot revealed higher agreement between both methods for heart rate
      and velocity values. Ventilatory anaerobic threshold occurred at a swimming
      velocity corresponding to 88% of maximal oxygen uptake and lactate concentration
      mean values at ventilatory and metabolic thresholds were lower than 3 mmol.L(-1).
      CONCLUSION: Swimming anaerobic metabolic threshold could be accurately estimated
      using ventilatory parameters. Moreover, ventilatory anaerobic threshold occurred
      at similar %VO2max than in other sports. The lactate concentration mean values at
      ventilatory and metabolic thresholds were lower than the reference value of 4
      mmol.L(-1) evidencing that, in highly trained swimmers, individualized values of
      anaerobic threshold should be used instead of general references.

PMID- 25069964
TI  - Feasibility of using a new generation wireless device for electrocardiographic
      monitoring of professional soccer players during an exercise test in field.

PMID- 25069966
TI  - Roles of the calcium sensing receptor in digestive physiology and pathophysiology
      (review).
AB  - Calcium participates in most of the biological processes in the human body. The
      calcium sensing receptor (CaSR), as an important regulator of calcium
      homeostasis, is expressed in all of the organs of the digestive system. CaSR
      plays a key role in gastrointestinal physiological function and in the occurrence
      of digestive disease. For example, the inactivation or mutation of the CaSR gene
      usually leads to one of several disorders of calcium metabolism. High dietary
      Ca2+ may stimulate CaSR activation and could both inhibit tumor development and
      increase the chemotherapeutic sensitivity of cancer cells in colon cancer
      tissues. Further, CaSR has also been reported to have a potential role in the
      treatment for diarrheal diseases and the form of pancreatitis that is associated
      with carbonate stones. Therefore, CaSR is an important target for treating
      digestive diseases, and the calcimimetics (CaSR agonist) have been confirmed as
      practical, feasible and effective clinical therapies for hyperparathyroidism.
      This review intends to explore the role of CaSR in digestive physiology and
      pathophysiology as well as current treatments utilizing CaSR-based therapeutics. 

PMID- 25069965
TI  - SMAD signaling regulates CXCL12 expression in the bone marrow niche, affecting
      homing and mobilization of hematopoietic progenitors.
AB  - We recently demonstrated that ex vivo activation of SMAD-independent bone
      morphogenetic protein 4 (BMP4) signaling in hematopoietic stem/progenitor cells
      (HSPCs) influences their homing into the bone marrow (BM). Here, we assessed
      whether alterations in BMP signaling in vivo affects adult hematopoiesis by
      affecting the BM niche. We demonstrate that systemic inhibition of SMAD-dependent
      BMP signaling by infusion of the BMP antagonist noggin (NGN) significantly
      increased CXCL12 levels in BM plasma leading to enhanced homing and engraftment
      of transplanted HSPCs. Conversely, the infusion of BMP7 but not BMP4, resulted in
      decreased HSPC homing. Using ST2 cells as an in vitro model of BM niche, we found
      that incubation with neutralizing anti-BMP4 antibodies, NGN, or dorsomorphin (DM)
      as well as knockdown of Smad1/5 and Bmp4, all enhanced CXCL12 production.
      Chromatin immunoprecipitation identified the SMAD-binding element in the CXCL12
      promoter to which SMAD4 binds. When deleted, increased CXCL12 promoter activity
      was observed, and NGN or DM no longer affected Cxcl12 expression. Interestingly,
      BMP7 infusion resulted in mobilization of only short-term HSCs, likely because
      BMP7 affected CXCL12 expression only in osteoblasts but not in other niche
      components. Hence, we describe SMAD-dependent BMP signaling as a novel regulator
      of CXCL12 production in the BM niche, influencing HSPC homing, engraftment, and
      mobilization.

PMID- 25069967
TI  - Stick or grip? Co-evolution of adhesive toepads and claws in Anolis lizards.
AB  - Exploring the relationship between phenotype and performance in an ecological and
      evolutionary context is crucial to understanding the adaptive nature of
      phenotypic traits. Despite their ubiquity in vertebrates, few studies have
      examined the functional and ecological significance of claw morphologies. Here we
      examine the adhesive toepad and claw system of Anolis lizards. Claw characters
      are significantly different between lizards classified as arboreal (perch
      height>=1m) and non-arboreal (perch height<1m). Arboreal species possess
      significantly higher and longer claws, and show trends toward decreased claw
      curvature and wider claw tip angles. Toepad size and claw length and height are
      tightly correlated with each other and with perch height, suggesting that the
      adhesive toepad and gripping claw have co-evolved to accommodate different
      habitats. The functional morphology and evolution of claws are ripe areas for
      future investigation. 

PMID- 25069968
TI  - Structural and electronic properties of uranium-encapsulated Au14 cage.
AB  - The structural properties of the uranium-encapsulated nano-cage U@Au14 are
      predicted using density functional theory. The presence of the uranium atom makes
      the Au14 structure more stable than the empty Au14-cage, with a triplet ground
      electronic state for U@Au14. Analysis of the electronic structure shows that the
      two frontier single-occupied molecular orbital electrons of U@Au14 mainly
      originate from the 5f shell of the U atom after charge transfer. Meanwhile, the
      bonding orbitals and charge population indicate that the designed U@Au14 nano
      cage structure is stabilized by ionocovalent interactions. The current findings
      provide theoretical basis for future syntheses and further study of actinide
      doped gold nanoclusters, which might subsequently facilitate applications of such
      structure in radio-labeling, nanodrug carrier and other biomedical applications. 

PMID- 25069969
TI  - Hepatitis E virus infection in farmed rabbits and swine in the Eastern Chinese
      city Lianyungang: showing no potential interspecies transmission.
AB  - Rabbit HEV isolated recently from farmed rabbits in China has been shown
      experimentally to be able to infect both cynomolgus macaques and pigs. The
      purpose of the present study was to investigate the extent to which cross-species
      transmission of rabbit HEV in farm settings is a significant factor in the spread
      of this zoonotic infection. Rabbit and swine feces were collected from the same
      area in Eastern China (Lianyungang City) and analyzed by RT-PCR. Partial genome
      sequencing of a 365 bp region of ORF2 from the HEV positive rabbit samples
      revealed that they had 92-99% sequence identity with rabbit strains (rbIM163-c1
      and rbIM004) isolated from Inner Mongolia. Similarly, sequencing of a 765 bp
      region of ORF2 of HEV positive swine samples showed 96-98% sequence identity with
      genotype 4d isolates collected from patients in the Yantai and Nanjing regions of
      China. By contrast, the sequence identity between the rabbit and swine isolates
      was only 73-75%, with no molecular biological evidence of interspecies
      transmission having occurred. It is concluded that whilst interspecies infection
      with rabbit HEV can be achieved experimentally, in the field it is not a
      significant factor in zoonotic disease transmission at least in the area of China
      where this study was undertaken.

PMID- 25069970
TI  - Feeding value of hays of tropical forage legumes in pigs: Vigna unguiculata,
      Psophocarpus scandens, Pueraria phaseoloides and Stylosanthes guianensis.
AB  - The effects of four tropical forage legume hays (Vigna unguiculata, Psophocarpus
      scandens, Pueraria phaseoloides and Stylosanthes guianensis) on voluntary feed
      intake (VFI) and their nutritive value were studied in growing pigs using a corn
      soybean meal-based diet containing varying proportions of forage legume hays (0,
      10, 20 and 40 % or 0, 12.5 and 25 % for VFI and nutritive value determination,
      respectively). There was no difference in VFI between species (P > 0.20), but a
      linear response to forage inclusion level (P < 0.05) was observed decreasing from
      126 for 0 % to approximately 84 g/kg of body weight for the 40 % forage diets,
      except for V. unguiculata, where the response was quadratic (P = 0.01). All four
      forage species linearly decreased the total tract apparent digestibility (TTAD)
      from 0.76 to 0.61, 0.80 to 0.68, 0.54 to 0.40 and 0.58 to 0.31 except for S.
      guianensis (0.44) for DM, N, NDF and N retention, respectively. Differences in
      digestibility (P < 0.05) between species were also observed. Due to their
      negative influence on the overall digestibility, the contribution of hays should
      not exceed 12.5 %, except for S. guianensis, in which N retention remained quite
      high (0.44) at the highest inclusion level (25 %). P. phaseoloides hay should be
      avoided in pigs as it combines the lowest VFI with the lowest nutrient
      digestibility.

PMID- 25069971
TI  - Cassava starch factory residues in the diet of slow-growing broilers.
AB  - The objective of this study was to evaluate the effect of inclusion of dehydrated
      cassava starch residue (DCSR) on the performance, gastrointestinal tract
      characteristics and carcass traits of ISA Label JA57 slow-growing broilers. A
      total of 510 broilers at 21 were distributed in a randomized experimental design
      with 5 treatments (2, 4, 6, 8, and 10 % DCSR inclusion) and a control group, 5
      replicates, and 17 birds per experimental unit. The DCSR inclusion from 21 to 49
      days of age negatively influenced (P < 0.05) weight gain and feed intake and did
      not affect (P > 0.05) feed conversion in the broilers with increasing of DCSR
      inclusion. From 21 to 79 days, DCSR inclusion impaired (P < 0.05) weight gain,
      feed conversion, and poultry litter quality with increasing of DCSR inclusion.
      The level of blood triglycerides showed a quadratic response (P < 0.05) at 79
      days of age with the highest value predicted to occur at 5.45 % of DCSR
      inclusion. DCSR levels affected (P < 0.05) the gastrointestinal organ
      characteristics, cecal content pH, and pigmentation of the shank, breast, and
      thigh meat of the birds but did not alter (P > 0.05) the other parameters of
      carcass quality and yield, cuts, and percentage of abdominal fat. In conclusion,
      DCSR inclusion levels above 2 % compromised broiler performance.

PMID- 25069973
TI  - An assistive device for congenital central hypoventilation syndrome outpatients
      during sleep.
AB  - Congenital Central Hypoventilation Syndrome is a genetic disease characterized by
      alveolar hypoventilation and autonomic dysregulation. Patients have
      hypoventilations, especially during sleep, conditioning hypercapnia which can
      lead to neurological damage and death. They therefore need mechanical
      ventilators, that provide sufficient gas exchange, and pulse-oximeters that
      monitor oxy-hemoglobin blood concentration. Due to the restrictions regarding
      domiciliary assistive devices, the presence of a caregiver is required all night
      long. Currently, the only alarm systems available are the ones integrated in the
      ventilators and monitoring systems. During the night, multiple false alarms may
      occur, interrupting the sleep and causing anxiety. In this work we describe an
      assistive device that acquires real-time data from a pulse-oximeter, provides a
      multisensory stimulation if oxygen saturation falls under a certain threshold,
      and wakes up the patient if the hypoxia is severe. Tests on healthy subjects have
      shown that the device guarantees rapid awakenings, with a stimulator-dependent
      efficacy, and that it does not affect sleep efficiency. The purpose of the device
      is to determine a gentle awakening if mild hypoxia conditions persist, and to
      assure rapid awakening when a severe hypoxia occurs, reducing false alarms,
      improving the quality of sleep and increasing the self-sufficiency of the
      patients. 

PMID- 25069975
TI  - Introducing rapid diagnostic tests for malaria into drug shops in Uganda: design
      and implementation of a cluster randomized trial.
AB  - BACKGROUND: An intervention was designed to introduce rapid diagnostics tests for
      malaria (mRDTs) into registered drug shops in Uganda to encourage rational and
      appropriate treatment of malaria with artemisinin-based combination therapy
      (ACT). We conducted participatory training of drug shop vendors and implemented
      supporting interventions to orientate local communities (patients) and the public
      sector (health facility staff and district officials) to the behavioral changes
      in diagnosis, treatment and referral being introduced in drug shops. The
      intervention was designed to be evaluated through a cluster randomized trial. In
      this paper, we present detailed design, implementation and evaluation experiences
      in order to help inform future studies of a complex nature. METHODS: Three
      preparatory studies (formative, baseline and willingness-to-pay) were conducted
      to explore perceptions on diagnosis and treatment of malaria at drug shops, and
      affordable prices for mRDTs and ACTs in order to inform the design of the
      intervention and implementation modalities. The intervention required careful
      design with the intention to be acceptable, sustainable and effective. Critical
      components of intervention were: community sensitization and creating awareness,
      training of drug shop vendors to diagnose malaria with mRDTs, treat and refer
      customers to formal health facilities, giving pre-referral rectal artesunate and
      improved record-keeping. The primary outcome was the proportion of patients
      receiving appropriately-targeted treatment with ACT, evaluated against microscopy
      on a research blood slide. RESULTS: Introducing mRDTs in drug shops may seem
      simple, but our experience of intervention design, conduct and evaluation showed
      this to be a complex process requiring multiple interventions and evaluation
      components drawing from a combination of epidemiological, social science and
      health economics methodologies. The trial was conducted in phases sequenced such
      that each benefited from the other. CONCLUSIONS: The main challenges in designing
      this trial were maintaining a balance between a robust intervention to support
      effective behaviour change and introducing practices that would be sustainable in
      a real-life situation in tropical Africa; as well as achieving a detailed
      evaluation without inadvertently influencing prescribing behaviour. TRIAL
      REGISTRATION: NCT01194557 registered with ClinicalTrials.gov 2 September 2010.

PMID- 25069976
TI  - Migration of dendritic cells facilitates systemic dissemination of Burkholderia
      pseudomallei.
AB  - Burkholderia pseudomallei, the etiological agent for melioidosis, is an important
      cause of community-acquired sepsis in northern Australia and northeast Thailand.
      Due to the rapid dissemination of disease in acute melioidosis, we hypothesized
      that dendritic cells (DC) could act as a vehicle for dissemination of B.
      pseudomallei. Therefore, this study investigated the effect of B. pseudomallei
      infection on DC migration capacity and whether migration of DC enabled
      transportation of B. pseudomallei from the site of infection. B. pseudomallei
      stimulated significantly increased migration of bone marrow-derived DC (BMDC),
      both in vitro and in vivo, compared to uninfected BMDC. Furthermore, migration of
      BMDC enabled significantly increased in vitro trafficking of B. pseudomallei and
      in vivo dissemination of B. pseudomallei to secondary lymphoid organs and lungs
      of C57BL/6 mice. DC within the footpad infection site of C57BL/6 mice also
      internalized B. pseudomallei and facilitated dissemination. Although DC have
      previously been shown to kill intracellular B. pseudomallei in vitro, the
      findings of this study demonstrate that B. pseudomallei-infected DC facilitate
      the systemic spread of this pathogen. 

PMID- 25069977
TI  - Staphylococcus aureus hyaluronidase is a CodY-regulated virulence factor.
AB  - Staphylococcus aureus is a Gram-positive pathogen that causes a diverse range of
      bacterial infections. Invasive S. aureus strains secrete an extensive arsenal of
      hemolysins, immunomodulators, and exoenzymes to cause disease. Our studies have
      focused on the secreted enzyme hyaluronidase (HysA), which cleaves the hyaluronic
      acid polymer at the beta-1,4 glycosidic bond. In the study described in this
      report, we have investigated the regulation and contribution of this enzyme to S.
      aureus pathogenesis. Using the Nebraska Transposon Mutant Library (NTML), we
      identified eight insertions that modulate extracellular levels of HysA activity.
      Insertions in the sigB operon, as well as in genes encoding the global regulators
      SarA and CodY, significantly increased HysA protein levels and activity. By
      altering the availability of branched-chain amino acids, we further demonstrated
      CodY-dependent repression of HysA activity. Additionally, through mutation of the
      CodY binding box upstream of hysA, the repression of HysA production was lost,
      suggesting that CodY is a direct repressor of hysA expression. To determine
      whether HysA is a virulence factor, a DeltahysA mutant of a community-associated
      methicillin-resistant S. aureus (CA-MRSA) USA300 strain was constructed and found
      to be attenuated in a neutropenic, murine model of pulmonary infection. Mice
      infected with this mutant strain exhibited a 4-log-unit reduction in bacterial
      burden in their lungs, as well as reduced lung pathology and increased levels of
      pulmonary hyaluronic acid, compared to mice infected with the wild-type, parent
      strain. Taken together, these results indicate that S. aureus hyaluronidase is a
      CodY-regulated virulence factor. 

PMID- 25069978
TI  - Helicobacter pylori infection introduces DNA double-strand breaks in host cells.
AB  - Gastric cancer is an inflammation-related malignancy related to long-standing
      acute and chronic inflammation caused by infection with the human bacterial
      pathogen Helicobacter pylori. Inflammation can result in genomic instability.
      However, there are considerable data that H. pylori itself can also produce
      genomic instability both directly and through epigenetic pathways. Overall, the
      mechanisms of H. pylori-induced host genomic instabilities remain poorly
      understood. We used microarray screening of H. pylori-infected human gastric
      biopsy specimens to identify candidate genes involved in H. pylori-induced host
      genomic instabilities. We found upregulation of ATM expression in vivo in gastric
      mucosal cells infected with H. pylori. Using gastric cancer cell lines, we
      confirmed that the H. pylori-related activation of ATM was due to the
      accumulation of DNA double-strand breaks (DSBs). DSBs were observed following
      infection with both cag pathogenicity island (PAI)-positive and -negative
      strains, but the effect was more robust with cag PAI-positive strains. These
      results are consistent with the fact that infections with both cag PAI-positive
      and -negative strains are associated with gastric carcinogenesis, but the risk is
      higher in individuals infected with cag PAI-positive strains. 

PMID- 25069979
TI  - Conserved oligopeptide permeases modulate sporulation initiation in Clostridium
      difficile.
AB  - The anaerobic gastrointestinal pathogen Clostridium difficile must form a
      metabolically dormant spore to survive in oxygenic environments and be
      transmitted from host to host. The regulatory factors by which C. difficile
      initiates and controls the early stages of sporulation in C. difficile are not
      highly conserved in other Clostridium or Bacillus species. Here, we investigated
      the role of two conserved oligopeptide permeases, Opp and App, in the regulation
      of sporulation in C. difficile. These permeases are known to positively affect
      sporulation in Bacillus species through the import of sporulation-specific quorum
      sensing peptides. In contrast to other spore-forming bacteria, we discovered that
      inactivating these permeases in C. difficile resulted in the earlier expression
      of early sporulation genes and increased sporulation in vitro. Furthermore,
      disruption of opp and app resulted in greater virulence and increased the amounts
      of spores recovered from feces in the hamster model of C. difficile infection.
      Our data suggest that Opp and App indirectly inhibit sporulation, likely through
      the activities of the transcriptional regulator SinR and its inhibitor, SinI.
      Taken together, these results indicate that the Opp and App transporters serve a
      different function in controlling sporulation and virulence in C. difficile than
      in Bacillus subtilis and suggest that nutrient availability plays a significant
      role in pathogenesis and sporulation in vivo. This study suggests a link between
      the nutritional status of the environment and sporulation initiation in C.
      difficile. 

PMID- 25069980
TI  - Tc52 amino-terminal-domain DNA carried by attenuated Salmonella enterica serovar
      Typhimurium induces protection against a Trypanosoma cruzi lethal challenge.
AB  - In this work we immunized mice with DNA encoding full-length Tc52 or its amino-
      or carboxy-terminal (N- and C-term, respectively) domain carried by attenuated
      Salmonella as a DNA delivery system. As expected, Salmonella-mediated DNA
      delivery resulted in low antibody titers and a predominantly Th1 response, as
      shown by the ratio of IgG2a/IgG1-specific antibodies. Despite modest expression
      of Tc52 in trypomastigotes, the antibodies elicited by vaccination were able to
      mediate lysis of the trypomastigotes in the presence of complement and inhibit
      their invasion of mammal cells in vitro. The strongest functional activity was
      observed with sera from mice immunized with Salmonella carrying the N-term domain
      (SN-term), followed by Tc52 (STc52), and the C-term domain (SC-term). All
      immunized groups developed strong cellular responses, with predominant activation
      of Th1 cells. However, mice immunized with SN-term showed higher levels of
      interleukin-10 (IL-10), counterbalancing the inflammatory reaction, and also
      strong activation of Tc52-specific gamma interferon-positive (IFN-gamma(+))
      CD8(+) T cells. In agreement with this, although all prototypes conferred
      protection against infection, immunization with SN-term promoted greater
      protection than that with SC-term for all parameters tested and slightly better
      protection than that with STc52, especially in the acute stage of infection. We
      conclude that the N-terminal domain of Tc52 is the section of the protein that
      confers maximal protection against infection and propose it as a promising
      candidate for vaccine development. 

PMID- 25069981
TI  - Epithelial anion transporter pendrin contributes to inflammatory lung pathology
      in mouse models of Bordetella pertussis infection.
AB  - Pertussis disease, characterized by severe and prolonged coughing episodes, can
      progress to a critical stage with pulmonary inflammation and death in young
      infants. However, there are currently no effective treatments for pertussis. We
      previously studied the role of pertussis toxin (PT), an important Bordetella
      pertussis virulence factor, in lung transcriptional responses to B. pertussis
      infection in mouse models. One of the genes most highly upregulated in a PT
      dependent manner encodes an epithelial transporter of bicarbonate, chloride, and
      thiocyanate, named pendrin, that contributes to asthma pathology. In this study,
      we found that pendrin expression is upregulated at both gene and protein levels
      in the lungs of B. pertussis-infected mice. Pendrin upregulation is associated
      with PT production by the bacteria and with interleukin-17A (IL-17A) production
      by the host. B. pertussis-infected pendrin knockout (KO) mice had higher lung
      bacterial loads than infected pendrin-expressing mice but had significantly
      reduced levels of lung inflammatory pathology. However, reduced pathology did not
      correlate with reduced inflammatory cytokine expression. Infected pendrin KO mice
      had higher levels of inflammatory cytokines and chemokines than infected pendrin
      expressing mice, suggesting that these inflammatory mediators are less active in
      the airways in the absence of pendrin. In addition, treatment of B. pertussis
      infected mice with the carbonic anhydrase inhibitor acetazolamide reduced lung
      inflammatory pathology without affecting pendrin synthesis or bacterial loads.
      Together these data suggest that PT contributes to pertussis pathology through
      the upregulation of pendrin, which promotes conditions favoring inflammatory
      pathology. Therefore, pendrin may represent a novel therapeutic target for
      treatment of pertussis disease. 

PMID- 25069982
TI  - Distinct contributions of interleukin-1alpha (IL-1alpha) and IL-1beta to innate
      immune recognition of Pseudomonas aeruginosa in the lung.
AB  - The bacterial pathogen Pseudomonas aeruginosa causes acute infections associated
      with significant morbidity and mortality. P. aeruginosa elicits strong innate
      immune responses in immunocompetent hosts, and the resulting recruitment of
      neutrophils to the site of infection is necessary for bacterial clearance. P.
      aeruginosa lipopolysaccharide and flagellin are recognized by extracellular Toll
      like receptors, but the most rapid responses to infection occur when cytosolic
      receptors sense flagellin or type 3 secretion system (T3SS) structural proteins.
      The subsequent activation of the NLRC4 inflammasome and caspase-1 generates an
      interleukin-1beta (IL-1beta) signal that is required for the rapid neutrophilic
      response. A T3SS effector, exotoxin U (ExoU), can inhibit activation of the NLRC4
      inflammasome and caspase-1. Thus, our observation that IL-1 receptor (IL-1R)
      mediated signals were still required to initiate a response to ExoU-producing
      bacteria was unexpected. As both IL-1alpha and IL-1beta signal via the IL-1R, we
      examined immune responses in mice lacking either of these cytokines. IL-1beta
      deficient mice responded to ExoU-producing P. aeruginosa bacteria similarly to
      wild-type animals; however, IL-1alpha-deficient mice had an attenuated immune
      response. The situation was reversed following infections by ExoU-negative
      bacteria: here, IL-1alpha was dispensable for neutrophil recruitment, while IL
      1beta was required. IL-1alpha secretion by macrophages infected with ExoU
      producing P. aeruginosa isolates was independent of both caspase-1 and caspase
      11. This study documents distinct roles for IL-1alpha and IL-1beta in the
      response to P. aeruginosa infection as a function of the T3SS effectors produced
      by the infecting strain. The redundancy of these two cytokines nonetheless allows
      the infected host to mount a response to ExoU-positive and -negative bacterial
      isolates. 

PMID- 25069983
TI  - Overlapping functionality of the Pht proteins in zinc homeostasis of
      Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a globally significant pathogen that causes a range
      of diseases, including pneumonia, sepsis, meningitis, and otitis media. Its
      ability to cause disease depends upon the acquisition of nutrients from its
      environment, including transition metal ions such as zinc. The pneumococcus
      employs a number of surface proteins to achieve this, among which are four highly
      similar polyhistidine triad (Pht) proteins. It has previously been established
      that these proteins collectively aid in the delivery of zinc to the ABC
      transporter substrate-binding protein AdcAII. Here we have investigated the
      contribution of each individual Pht protein to pneumococcal zinc homeostasis by
      analyzing mutant strains expressing only one of the four pht genes. Under
      conditions of low zinc availability, each of these mutants showed superior growth
      and zinc accumulation profiles relative to a mutant strain lacking all four
      genes, indicating that any of the four Pht proteins are able to facilitate
      delivery of zinc to AdcAII. However, optimal growth and zinc accumulation in
      vitro and pneumococcal survival and proliferation in vivo required production of
      all four Pht proteins, indicating that, despite their overlapping functionality,
      the proteins are not dispensable without incurring a fitness cost. We also show
      that surface-attached forms of the Pht proteins are required for zinc recruitment
      and that they do not contribute to defense against extracellular zinc stress. 

PMID- 25069984
TI  - Platelet activation by Streptococcus pyogenes leads to entrapment in platelet
      aggregates, from which bacteria subsequently escape.
AB  - Platelet activation and aggregation have been reported to occur in response to a
      number of Gram-positive pathogens. Here, we show that platelet aggregates induced
      by Streptococcus pyogenes were unstable and that viable bacteria escaped from the
      aggregates over time. This was not due to differential activation in response to
      the bacteria compared with physiological activators. All the bacterial isolates
      induced significant platelet activation, including integrin activation and alpha
      and dense-granule release, at levels equivalent to those induced by potent
      physiological platelet activators that induced stable aggregates. The ability to
      escape the aggregates and to resist the antibacterial effects of platelets was
      dependent on active protein synthesis by the bacteria within the aggregate. We
      conclude that S. pyogenes bacteria can temporarily cover themselves with
      activated platelets, and we propose that this may facilitate survival of the
      bacteria in the presence of platelets. 

PMID- 25069985
TI  - BB0238, a presumed tetratricopeptide repeat-containing protein, is required
      during Borrelia burgdorferi mammalian infection.
AB  - The Lyme disease spirochete, Borrelia burgdorferi, occupies both a tick vector
      and mammalian host in nature. Considering the unique enzootic life cycle of B.
      burgdorferi, it is not surprising that a large proportion of its genome is
      composed of hypothetical proteins not found in other bacterial pathogens. bb0238
      encodes a conserved hypothetical protein of unknown function that is predicted to
      contain a tetratricopeptide repeat (TPR) domain, a structural motif responsible
      for mediating protein-protein interactions. To evaluate the role of bb0238 during
      mammalian infection, a bb0238-deficient mutant was constructed. The bb0238 mutant
      was attenuated in mice infected via needle inoculation, and complementation of
      bb0238 expression restored infectivity to wild-type levels. bb0238 expression
      does not change in response to varying culture conditions, and thus, it appears
      to be constitutively expressed under in vitro conditions. bb0238 is expressed in
      murine tissues during infection, though there was no significant change in
      expression levels among different tissue types. Localization studies indicate
      that BB0238 is associated with the inner membrane of the spirochete and is
      therefore unlikely to promote interaction with host ligands during infection. B.
      burgdorferi clones containing point mutations in conserved residues of the
      putative TPR motif of BB0238 demonstrated attenuation in mice that was comparable
      to that in the bb0238 deletion mutant, suggesting that BB0238 may contain a
      functional TPR domain. 

PMID- 25069986
TI  - PafR, a novel transcription regulator, is important for pathogenesis in
      uropathogenic Escherichia coli.
AB  - The metV genomic island in the chromosome of uropathogenic Escherichia coli
      (UPEC) encodes a putative transcription factor and a sugar permease of the
      phosphotransferase system (PTS), which are predicted to compose a Bgl-like
      sensory system. The presence of these two genes, hereby termed pafR and pafP,
      respectively, has been previously shown to correlate with isolates causing
      clinical syndromes. We show here that deletion of both genes impairs the ability
      of the resulting mutant to infect the CBA/J mouse model of ascending urinary
      tract infection compared to that of the parent strain, CFT073. Expressing the two
      genes in trans in the two-gene knockout mutant complemented full virulence.
      Deletion of either gene individually generated the same phenotype as the double
      knockout, indicating that both pafR and pafP are important to pathogenesis. We
      screened numerous environmental conditions but failed to detect expression from
      the promoter that precedes the paf genes in vitro, suggesting that they are in
      vivo induced (ivi). Although PafR is shown here to be capable of functioning as a
      transcriptional antiterminator, its targets in the UPEC genome are not known.
      Using microarray analysis, we have shown that expression of PafR from a
      heterologous promoter in CFT073 affects expression of genes related to bacterial
      virulence, biofilm formation, and metabolism. Expression of PafR also inhibits
      biofilm formation and motility. Taken together, our results suggest that the paf
      genes are implicated in pathogenesis and that PafR controls virulence genes, in
      particular biofilm formation genes. 

PMID- 25069987
TI  - Substance misuse among adolescents: to screen or not to screen?

PMID- 25069988
TI  - Preparation of starch nanoparticles in a water-in-ionic liquid microemulsion
      system and their drug loading and releasing properties.
AB  - An ionic liquid microemulsion consisting of 1-butyl-3-methylimidazolium
      hexafluorophosphate ([Bmim]PF6), surfactant TX-100, 1-butanol, and water was
      prepared. The water-in-[Bmim]PF6 (W/IL), bicontinuous, and [Bmim]PF6-in-water
      (IL/W) microregions of the microemulsion were identified by conductivity
      measurements. Starch nanoparticles with a mean diameter of 91.4 nm were
      synthesized with epichlorohydrin as cross-linker through W/IL microemulsion cross
      linking reaction at 50  degrees C for 4 h. Fourier transform infrared
      spectroscopy (FTIR) data demonstrated the formation of cross-linking bonds in
      starch molecules. Scanning electron microscopy (SEM) revealed that starch
      nanoparticles were spherical and that some particles showed aggregation
      formation. Furthermore, drug loading and releasing properties of starch
      nanoparticles were investigated with mitoxantrone hydrochloride as a drug model.
      This work provides an efficient and environmentally friendly approach for the
      preparation of starch nanoparticles, which is beneficial to their further
      application.

PMID- 25069989
TI  - Dengue virus E glycoprotein production in transgenic rice callus.
AB  - Dengue is a disease caused by dengue virus and represents the most important
      arthropod-borne viral disease in humans. Dengue virus enters host cells via
      binding of envelope glycoprotein (E) to a receptor. In this study, plant
      expression vectors containing native and synthetic glycoprotein E genes (sE)
      modified based on plant-optimized codon usage and fused with an ER retention
      signal were constructed under control of the rice amylase 3D promoter expression
      system. Plant expression vectors were introduced into rice callus (Oryza sativa
      L. cv. Dongin) via particle bombardment-mediated transformation. The integration
      and expression of target genes were confirmed in the transgenic callus by genomic
      DNA PCR and Northern blot analyses, respectively. The plant-codon optimized sE
      gene with an ER retention signal showed high protein production levels based on
      Western blot analysis of approximately 18.5 ug/g dried calli weight by immunoblot
      based densitometric analysis. These results suggest that the plant-codon
      optimized sE gene with an ER retention signal was highly produced in the
      transgenic rice callus. 

PMID- 25069990
TI  - Ectopic TSH-secreting pituitary tumor: a case report and review of prior cases.
AB  - BACKGROUND: Ectopic TSH-secreting pituitary adenoma (TSH-oma) is a very unusual
      disorder. To date, there are only four cases reported. It is difficult to
      distinguish ectopic cases from both regular TSH-omas and resistance to thyroid
      hormone (RTH). CASE PRESENTATION: A newly identified case of ectopic TSH-oma
      arising from the nasal pharynx was described, and reports of four prior cases
      were reviewed. The patient was a 41-year-old male who developed what appeared to
      be typical hyperthyroidism and atrial fibrillation in 2009. Thyroid function
      tests showed elevated basal levels of free T3 (FT3, 24.08 pmol/L), free T4 (FT4,
      75.73 pmol/L), and serum TSH (7.26 MUIU/ml). Both TSH-oma and resistance to
      thyroid hormone syndrome were considered. TRH stimulating test was negative,
      whereas octreotide inhibition test showed a reduction in TSH by 30.8%.
      Furthermore, a large space-occupying lesion located at the nasopharynx was found
      by computed tomography and magnetic resonance imaging (MRI). A normal pituitary
      was visualized. Ectopic TSH-oma was preliminarily established. Using an
      endoscopic endonasal approach, the tumor was resected. Histological features and
      immunophenotypes were consistent with those of TSH-secreting tumor. The levels of
      both free thyroxine and TSH returned to normal ranges the day after surgery and
      remained within normal range for 48 months. CONCLUSIONS: Although exceedingly
      rare, ectopic TSH-oma should be considered for patients with inappropriate
      secretion of TSH with hyperthyroidism and pituitary tumor undetectable by
      computed tomography and MRI. To our knowledge, this is the first case followed up
      more than 4 years. The characteristics and successful interventions summarized in
      this report provide a guideline for clinicians.

PMID- 25069991
TI  - Arterial imaging outcomes and cardiovascular risk factors in recently menopausal
      women: a randomized trial.
AB  - BACKGROUND: Whether menopausal hormone therapy (MHT) protects against
      cardiovascular disease (CVD) remains unclear. OBJECTIVE: To assess
      atherosclerosis progression and CVD risk factors after MHT initiated in early
      menopause. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov:
      NCT00154180). SETTING: Nine U.S. academic centers. PARTICIPANTS: Healthy
      menopausal women aged 42 to 58 years between 6 and 36 months from last menses
      without prior CVD events who had a coronary artery calcium (CAC) score less than
      50 Agatston units and had not received estrogen or lipid-lowering therapy for at
      least 90 days. INTERVENTION: Oral conjugated equine estrogens (o-CEE), 0.45 mg/d,
      or transdermal 17beta-estradiol (t-E2), 50 mcg/d, each with 200 mg of oral
      progesterone for 12 days per month, or placebo for 48 months. MEASUREMENTS:
      Primary end point was annual change in carotid artery intima-media thickness
      (CIMT). Secondary end points included changes in markers of CVD risk. RESULTS: Of
      727 randomly assigned women, 89.3% had at least 1 follow-up CIMT and 79.8% had
      CIMT at 48 months. Mean CIMT increases of 0.007 mm/y were similar across groups.
      The percentages of participants in whom CAC score increased did not differ
      significantly across groups. No changes in blood pressure were observed with o
      CEE or t-E2. Low- and high-density lipoprotein cholesterol levels improved and
      levels of C-reactive protein and sex hormone-binding globulin but not interleukin
      6 increased with o-CEE. Insulin resistance decreased with t-E2. Serious adverse
      events did not differ by treatment. LIMITATION: Power to compare clinical events
      was insufficient. CONCLUSION: Four years of early MHT did not affect progression
      of atherosclerosis despite improving some markers of CVD risk. PRIMARY FUNDING
      SOURCE: Aurora Foundation.

PMID- 25069996
TI  - Synthesis, characterization, and in vitro evaluation of new coordination
      complexes of platinum(II) and rhenium(I) with a ligand targeting the translocator
      protein (TSPO).
AB  - The 18 kDa translocator protein (TSPO) is overexpressed in many types of cancers
      and is also abundant in activated microglial cells occurring in inflammatory
      neurodegenerative diseases. The TSPO-selective ligand 2-(8-(2-(bis-(pyridin-2-yl
      methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N
      dipropylacetamide (CB256), which fulfills the requirements of a bifunctional
      chelate approach, has been used to synthesize coordination complexes containing
      either Pt (1) or Re (3), or both metal ions (2). The new metal complexes showed a
      cellular uptake markedly greater than that of the precursor metallic compounds
      and were also able to induce apoptosis in C6 glioma cells. The good cytotoxicity
      of the free ligand CB256 towards C6, A2780, and A2780cisR tumor cell lines was
      attenuated after coordination of the dipicolylamine moiety to Pt while
      coordination of the imidazopyridine residue to Re reduces the affinity towards
      TSPO. The results of the present investigation are essential for the design of
      new imidazopyridine bifunctional chelate ligands targeted to TSPO.

PMID- 25069997
TI  - Every Marine a rifleman: the 4 + 1 fellowship model.

PMID- 25069998
TI  - Radiology journals in transition: a summary of the 2013 Intersociety Committee
      Summer Conference.
AB  - The digital and online revolution is having a profound impact on radiology
      journals, forcing a migration from print to online publication and altering
      traditional revenue streams needed to sustain the journals. The 2013 Intersociety
      Committee Summer Conference attendees reviewed the history of the development of
      radiology journals, explored the forces driving the transition from print to
      electronic publication, and examined the impact of the alteration of the
      traditional revenue streams, such as subscription and advertisement dollars, on
      the financial sustainability of journals. The attendees also discussed the
      international movement toward open access to journal content and its impact on a
      journal's financial viability. Lastly, the committee explored the perceived value
      of radiology journals based on readership type: academic, private practice, or
      industry.

PMID- 25069999
TI  - Treatment of lower extremity telangiectasias in women by foam sclerotherapy vs.
      Nd:YAG laser: a prospective, comparative, randomized, open-label trial.
AB  - BACKGROUND: Telangiectasias of the lower extremities are very common. There are
      no blinded, randomized, controlled clinical trials comparing laser modalities
      with the gold standard sclerotherapy, while the few available studies encompass
      small patients cohorts. OBJECTIVE: This prospective, randomized, open-label trial
      compares the efficacy of sclerotherapy with polidocanol vs. long-pulsed neodymium
      doped yttrium aluminium garnet (Nd:YAG) laser in the treatment of leg
      telangiectasias. PATIENTS AND METHODS: Fifty-six female patients with primary leg
      telangiectasias and reticular veins (C1A or SEpAS1PN) were included in the study.
      One leg was randomly assigned to get treatment with the multiple synchronized
      long-pulsed Nd:YAG laser, while the other received foam sclerotherapy with
      polidocanol 0.5%. The patients were treated in two sessions at intervals of 6
      weeks. The patients were evaluated by the handling physician after 6 weeks and 6
      months. Two investigators assessed blindly at the end of the study the
      photographs for clearing of the vessels using a six-point scale from 1 (no
      change) to 6 (100% cleared). Patients reported about pain sensation and outcome
      satisfaction. RESULTS: According to the handling dermatologist, at the last
      follow-up, there was an improvement of 30-40% with a median of 3 (IQR 2) and a
      good improvement of 50-70% with a median of 4 (IQR 2) after laser treatment and
      sclerotherapy respectively. In contrast, according to the blinded investigators,
      there was a median of 5 (IQR 1) with a very good improvement of >70% after both
      therapies. Improvement was achieved more quickly by sclerotherapy, although at
      the last follow-up visit there was no difference in clearance between the two
      groups as assessed by the blinded experts (P-value 0.84). The degree of patient's
      satisfaction was very good and similar with both therapeutic approaches. There
      was a significant difference (P-value 0.003) regarding pain perception between
      the types of therapy. Laser was felt more painful than sclerotherapy. CONCLUSION:
      Telangiectasias of the lower extremities can be successfully treated with either
      synchronized long-pulsed Nd:YAG laser or sclerotherapy. The 1064-nm long-pulsed
      Nd:YAG laser is associated with more pain and is suitable especially in case of
      needle phobia, allergy to sclerosants and in presence of small veins with
      telangiectatic matting, while sclerotherapy can also treat the feeder veins.

PMID- 25070000
TI  - MicroRNA-181 inhibits glioma cell proliferation by targeting cyclin B1.
AB  - Small non-coding RNAs from the microRNA family (miRs) are important elements in
      the posttranscriptional control of gene expression. miRs are known to regulate
      numerous cellular processes and are of crucial importance during development and
      in pathological conditions, including tumor initiation and progression. In the
      present study, the expression level of miR-181 was reduced in glioma tissues
      compared with the adjacent normal tissues. The enforced expression of miR-181 was
      able to inhibit cell proliferation in U251 and SHG-44 cells, while antisense miR
      181 oligonucleotides (antisense miR-181) enhanced cell proliferation. At the
      molecular level, these results further revealed that the expression of cyclin B1,
      a positive cell-cycle regulator, was negatively regulated by miR-181. Therefore,
      the data reported in the present study demonstrates that miR-181 is an important
      regulator in glioma. These results may contribute to improving the understanding
      of the key misregulated miRNAs in glioma. 

PMID- 25070001
TI  - Lifestyle and metabolic syndrome in adult survivors of childhood cancer: a report
      from the St. Jude Lifetime Cohort Study.
AB  - BACKGROUND: Childhood cancer survivors (CCS) are at an increased risk of
      developing metabolic syndrome (MetSyn), which may be reduced with lifestyle
      modifications. The purpose of this investigation was to characterize lifestyle
      habits and associations with MetSyn among CCS. METHODS: CCS who were >= 10 years
      from diagnosis, aged > 18 years, and participating in the St. Jude Lifetime
      Cohort Study completed medical and laboratory tests and a food frequency
      questionnaire. The Third Report of the National Cholesterol Education Program
      Adult Treatment Panel criteria were used to classify participants with MetSyn.
      Anthropometric, food frequency questionnaire, and self-reported physical activity
      data were used to characterize lifestyle habits according to World Cancer
      Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations.
      Those who met >= 4 of 7 recommendations were classified as having followed
      guidelines. Sex-stratified log-binomial regression models were used to evaluate
      associations between dietary/lifestyle habits and MetSyn, adjusted for age, age
      at cancer diagnosis, receipt of cranial radiotherapy, education, and household
      income. RESULTS: Among 1598 CCS (49.2% of whom were male, with a median age of
      32.7 years [range, 18.9 years-60.0 years]), 31.8% met criteria for MetSyn and
      27.0% followed WCRF/AICR guidelines. Females who did not follow WCRF/AICR
      guidelines were 2.4 times (95% confidence interval, 1.7-3.3) and males were 2.2
      times (95% confidence interval, 1.6-3.0) more likely to have MetSyn than those
      who followed WCRF/AICR guidelines. CONCLUSIONS: Adherence to a heart-healthy
      lifestyle is associated with a lower risk of MetSyn among CCS. There is a need to
      determine whether lifestyle interventions prevent or remediate MetSyn in CCS.

PMID- 25070003
TI  - Transdifferentiation of vascular smooth muscle cells to macrophage-like cells
      during atherogenesis.
AB  - RATIONALE: Atherosclerosis is a widespread and devastating disease, but the
      origins of cells within atherosclerotic plaques are not well defined. OBJECTIVE:
      To investigate the specific contribution of vascular smooth muscle cells (SMCs)
      to atherosclerotic plaque formation by genetic inducible fate mapping in mice.
      METHODS AND RESULTS: Vascular SMCs were genetically pulse-labeled using the
      tamoxifen-dependent Cre recombinase, CreER(T2), expressed from the endogenous
      SM22alpha locus combined with Cre-activatable reporter genes that were integrated
      into the ROSA26 locus. Mature SMCs in the arterial media were labeled by
      tamoxifen treatment of young apolipoprotein E-deficient mice before the
      development of atherosclerosis and then their fate was monitored in older
      atherosclerotic animals. We found that medial SMCs can undergo clonal expansion
      and convert to macrophage-like cells that have lost classic SMC marker expression
      and make up a major component of advanced atherosclerotic lesions. CONCLUSIONS:
      This study provides strong in vivo evidence for smooth muscle-to-macrophage
      transdifferentiation and supports an important role of SMC plasticity in
      atherogenesis. Targeting this type of SMC phenotypic conversion might be a novel
      strategy for the treatment of atherosclerosis, as well as other diseases with a
      smooth muscle component.

PMID- 25070002
TI  - Facial morphometrics of children with non-syndromic orofacial clefts in Tanzania.
AB  - BACKGROUND: Orofacial clefts (cleft lip/palate; CL/P) are among the most common
      congenital anomalies, with prevalence that varies among different ethnic groups.
      Craniofacial shape differences between individuals with CL/P and healthy controls
      have been widely reported in non-African populations. Knowledge of craniofacial
      shape among individuals with non-syndromic CL/P in African populations will
      provide further understanding of the ethnic and phenotypic variation present in
      non-syndromic orofacial clefts. METHODS: A descriptive cross-sectional study was
      carried out at Bugando Medical Centre, Tanzania, comparing individuals with
      unrepaired non-syndromic CL/P and normal individuals without orofacial clefts.
      Three-dimensional (3D) facial surfaces were captured using a non-invasive 3D
      camera. The corresponding 3D coordinates for 26 soft tissue landmarks were used
      to characterize facial shape. Facial shape variation within and between groups,
      based on Procrustes superimposed data, was studied using geometric morphometric
      methods. RESULTS: Facial shape of children with cleft lip differed significantly
      from the control group, beyond the cleft itself. The CL/P group exhibited
      increased nasal and mouth width, increased interorbital distance, and more
      prognathic premaxillary region. Within the CL/P group, PCA showed that facial
      shape variation is associated with facial height, nasal cavity width,
      interorbital distance and midfacial prognathism. The isolated cleft lip (CL) and
      combined cleft lip and palate (CLP) groups did not differ significantly from one
      another (Procrustes distance = 0.0416, p = 0.50). Procrustes distance permutation
      tests within the CL/P group showed a significant shape difference between
      unilateral clefts and bilateral clefts (Procrustes distance = 0.0728, p =
      0.0001). Our findings indicate the morphological variation is similar to those of
      studies of CL/P patients and their unaffected close relatives in non-African
      populations. CONCLUSION: The mean facial shape in African children with non
      syndromic CL/P differs significantly from children without orofacial clefts. The
      main differences involve interorbital width, facial width and midface
      prognathism. The axes of facial shape differences we observed are similar to the
      patterns seen in Caucasian populations, despite apparent differences in cleft
      prevalence and cleft type distribution. Similar facial morphology in individuals
      with CL/P in African and Caucasian populations suggests a similar aetiology.

PMID- 25070007
TI  - Specific amplification of gene encoding N-terminal region of catalase-peroxidase
      protein (KatG-N) for diagnosis of disseminated MAC disease in HIV patients.
AB  - Disseminated Mycobacterium avium-intracellulare complex (MAC) infection is
      considered as severe complication of advanced HIV/AIDS disease. Currently
      available various laboratory investigations have not only limited ability to
      discriminate between MAC infection and tuberculosis but are also laborious and
      time consuming. The aim of this study was, therefore, to design a molecular-based
      strategy for specific detection of MAC and its differentiation from Mycobacterium
      tuberculosis (M. tb) isolated from the blood specimens of HIV patients. A simple
      PCR was developed based on the amplification of 120-bp katG-N gene corresponding
      to the first 40 amino acids of N-terminal catalase-peroxidase (KatG) protein of
      Mycobacterium avium that shows only ~13% sequence homology by clustal W alignment
      to N-terminal region of M. tb KatG protein. This assay allowed the accurate and
      rapid detection of MAC bacteremia, distinguishing it from M. tb in a single PCR
      reaction without any need for sequencing or hybridization protocol to be
      performed thereafter. This study produced enough evidence that a significant
      proportion of Indian HIV patients have disseminated MAC bacteremia, suggesting
      the utility of M. avium katG-N gene PCR for early detection of MAC disease in HIV
      patients. 

PMID- 25070004
TI  - Field dependence study of in vivo brain (31) P MRS up to 16.4 T.
AB  - In vivo (31) P MRS provides a unique tool for studying bioenergetics of living
      organs. Although its utility has been limited by the relatively low (31) P NMR
      sensitivity, increasing magnetic field strength (B0 ) could significantly improve
      the quality and reliability of the (31) P MR spectra for biomedical research. To
      quantitatively understand the field dependence of in vivo (31) P MRS for brain
      applications, (31) P NMR sensitivity of phosphocreatine (PCr) in rat brains was
      measured and compared at 9.4 T and 16.4 T. Additionally, the linewidths and T1
      relaxation times of PCr and adenosine triphosphate (ATP) resonances obtained from
      human and animal brains over a wide B0 range from 4 T, 7 T, and 9.4 T to 16.4 T
      were examined and their field dependences were quantified. The results indicate
      an approximate 1.74-fold (31) P signal-to-noise ratio (SNR) gain for PCr at 16.4
      T compared with 9.4 T. An approximate power 1.4 dependence of (31) P SNR on B0
      was concluded. Substantial improvements in spectral resolution and significantly
      shortened T1 values of brain PCr and ATP were observed at high/ultrahigh fields,
      contributing to an additional sensitivity gain and spectral improvement. In
      summary, the overall findings from this study suggest that in vivo (31) P MRS
      should greatly benefit from high/ultrahigh fields for noninvasive assessment of
      altered bioenergetics and metabolic processes associated with brain function and
      neurological diseases.

PMID- 25070009
TI  - Does the Reciproc file remove root canal bacteria and endotoxins as effectively
      as multifile rotary systems?
AB  - AIM: To evaluate the effectiveness of Reciproc for the removal of cultivable
      bacteria and endotoxins from root canals in comparison with multifile rotary
      systems. METHODOLOGY: The root canals of forty human single-rooted mandibular pre
      molars were contaminated with an Escherichia coli suspension for 21 days and
      randomly assigned to four groups according to the instrumentation system: GI -
      Reciproc (VDW); GII - Mtwo (VDW); GIII - ProTaper Universal (Dentsply Maillefer);
      and GIV -FKG Race(TM) (FKG Dentaire) (n = 10 per group). Bacterial and endotoxin
      samples were taken with a sterile/apyrogenic paper point before (s1) and after
      instrumentation (s2). Culture techniques determined the colony-forming units
      (CFU) and the Limulus Amebocyte Lysate assay was used for endotoxin
      quantification. Results were submitted to paired t-test and anova. RESULTS: At
      s1, bacteria and endotoxins were recovered in 100% of the root canals
      investigated (40/40). After instrumentation, all systems were associated with a
      highly significant reduction of the bacterial load and endotoxin levels,
      respectively: GI - Reciproc (99.34% and 91.69%); GII - Mtwo (99.86% and 83.11%);
      GIII - ProTaper (99.93% and 78.56%) and GIV - FKG Race(TM) (99.99% and 82.52%) (P
      < 0.001). No statistical difference were found amongst the instrumentation
      systems regarding bacteria and endotoxin removal (P > 0.01). CONCLUSION: The
      reciprocating single file, Reciproc, was as effective as the multifile rotary
      systems for the removal of bacteria and endotoxins from root canals.

PMID- 25070008
TI  - Comparison of a new transport medium with universal transport medium at a
      tropical field site.
AB  - Limited data are available in rural Honduran settings describing the etiology of
      respiratory infections, partially due to limited specimen transport. A new
      molecular transport media (MTM) preserves released nucleic acid at ambient
      temperature for later detection. Prospective surveillance was conducted in a
      Honduran clinic to identify 233 children less than 5 years of age presenting with
      respiratory symptoms. We obtained 2 nasopharyngeal samples and stored 1 in
      PrimeStore(r) MTM at room temperature and 1 in universal transport media (UTM) at
      -80  degrees C. The specimens were then transported to Cincinnati Children's
      Hospital and tested for 16 respiratory viruses using a multiplex PCR panel. The 2
      specimen collection systems were similar for detecting the 4 most common viruses:
      influenza (Kappa = 0.7676, P < 0.0001), human metapneumovirus (Kappa = 0.8770, P
      < 0.0001), respiratory syncytial virus (Kappa = 0.6849, P < 0.0001), and
      parainfluenza (Kappa = 0.8796, P < 0.0001). These results suggest that clinical
      specimens transported via PrimeStore(r) MTM and UTM yield similar viral multiplex
      PCR results. 

PMID- 25070010
TI  - Huntingtin interacting protein 1 as a histopathologic adjunct in the diagnosis of
      Merkel cell carcinoma.
AB  - BACKGROUND: Huntington interacting protein 1 (HIP1), an antiapoptotic protein
      normally expressed in the brain, is highly expressed in Merkel cell carcinomas
      (MCCs). Given this, the aim of the current study was to ascertain the value of
      HIP1 as a histopathologic adjunct in the diagnosis of MCC. METHODS: In this
      retrospective study, archival material from 26 cases with a diagnosis of MCC
      and/or neuroendocrine carcinoma were retrieved from the pathology files of the
      Skin Pathology Laboratory (Boston University School of Medicine, Boston, MA,
      USA). Histopathologic sections of all cases were re-reviewed and the diagnosis
      confirmed. All patient data were de-identified. Immunohistochemical studies were
      performed using antibodies to HIP1 and cytokeratins (CK) 20 and 7. RESULTS: A
      semiquantitative scoring system for immunohistochemical expression of HIP1 was
      utilized by deriving a cumulative score (based on percentage positivity of cells
      and intensity of expression). Using a cut-off total score of 3 or more as
      positive, the total number of positive cases was 22 for HIP1, 24 for CK20, and 11
      for CK7. CONCLUSION: Comparing the results of HIP1 and CK20, there were four
      discordant pairs (three positive for CK20 but negative for HIP1 and one positive
      for HIP1 but negative for CK20). McNemar's test indicated that there was no
      statistical significance (P = 0.625), thereby implying a close agreement between
      the expression of HIP1 and CK20 in these neuroendocrine neoplasms.

PMID- 25070011
TI  - CD36, but not GPR120, is required for efficient fatty acid utilization during
      endurance exercise.
AB  - Fatty acids (FA) are an important energy source during exercise. In addition to
      its role as an energy supply for skeletal muscle, FA may activate signaling
      pathways that regulate gene expression. FA translocase/cluster of differentiation
      36 (CD36) and G protein-coupled receptor GPR120 are long-chain FA receptors. In
      this study, we investigated the impact of CD36 or GPR120 deletion on energy
      metabolism during exercise. CD36 has been reported to facilitate cellular
      transport and oxidation of FA during endurance exercise. We show that CD36
      deletion decreased exogenous FA oxidation during exercise, using a combination of
      (13)C-labeled FA oxidation measurement and indirect calorimetry. In contrast,
      GPR120 deletion had no observable effect on energy metabolism during exercise.
      Our results further substantiate that CD36-mediated FA transport plays an
      essential role in efficient FA oxidation during exercise. 

PMID- 25070013
TI  - Tidal volumes in spontaneously breathing preterm infants supported with
      continuous positive airway pressure.
AB  - OBJECTIVE: To describe changes in tidal volume (VT) and their correlation to
      changes in oxygen saturation and heart rate in spontaneously breathing preterm
      infants immediately after birth. STUDY DESIGN: In this prospective observational,
      2-center study, a flow sensor was attached to the facemask of spontaneously
      breathing infants born at <37 weeks' gestational age who received continuous
      positive airway pressure (CPAP) immediately after birth. Respiratory function,
      heart rate, and oxygen saturation were continuously recorded during spontaneous
      breathing. RESULTS: Fifty-five infants (mean [SD] gestational age 31 [26-36]
      weeks and birth weight 1647 [500] g) received mask CPAP in the delivery room.
      CPAP was started at a median (IQR) 90 (60-118) seconds after birth and was
      delivered for 720 (300-900) seconds. Median VT ranged between 4.2 and 5.8 mL/kg
      with the individual VT varied between 0.9 and 19.8 mL/kg. Overall, VT increased
      over the first few minutes after birth and decreased thereafter. The increase in
      saturation after birth lagged behind the published normal ranges for
      spontaneously breathing preterm infants without CPAP. CONCLUSIONS: The 50th
      percentile for spontaneous VT in preterm infants during mask CPAP ranged from 4.2
      to 5.8 mL/kg, with wide individual variation observed in the first minutes after
      birth. Preterm infants requiring CPAP after birth may take longer to achieve so
      called "normal" saturation targets.

PMID- 25070012
TI  - Neutrophil extracellular traps in cancer progression.
AB  - Neutrophils are being increasingly recognized as an important element in tumor
      progression. They have been shown to exert important effects at nearly every
      stage of tumor progression with a number of studies demonstrating that their
      presence is critical to tumor development. Novel aspects of neutrophil biology
      have recently been elucidated and its contribution to tumorigenesis is only
      beginning to be appreciated. Neutrophil extracellular traps (NETs) are neutrophil
      derived structures composed of DNA decorated with antimicrobial peptides. They
      have been shown to trap and kill microorganisms, playing a critical role in host
      defense. However, their contribution to tumor development and metastasis has
      recently been demonstrated in a number of studies highlighting NETs as a
      potentially important therapeutic target. Here, studies implicating NETs as
      facilitators of tumor progression and metastasis are reviewed. In addition,
      potential mechanisms by which NETs may exert these effects are explored. Finally,
      the ability to target NETs therapeutically in human neoplastic disease is
      highlighted. 

PMID- 25070014
TI  - Nurturing Cultural Change in Care for Older People: Seeing the Cherry Tree
      Blossom.
AB  - There is a need for person-centred approaches and empowerment of staff within the
      residential care for older people; a movement called 'culture change'. There is
      however no single path for achieving culture change. With the aim of increasing
      understandings about cultural change processes and the promotion of cultural
      values and norms associated with person-centred practices, this article presents
      an action research project set on a unit in the Netherlands providing care for
      older people with dementia. The project is presented as a case study. This study
      examines what has contributed to the improvement of participation of older people
      with dementia in daily occupational and leisure activities according to
      practitioners. Data was collected by participant observation, interviews and
      focus groups. The results show that simultaneous to the improvement of the older
      people's involvement in daily activities a cultural transformation took place and
      that the care became more person-centred. Spontaneous interactions and responses
      rather than planned interventions, analysis and reflection contributed to this.
      Furthermore, it proved to be beneficial that the process of change and the
      facilitation of that process reflected the same values as those underlying the
      cultural change. It is concluded that changes arise from dynamic, interactive and
      non-linear processes which are complex in nature and difficult to predict and to
      control. Nevertheless, managers and facilitators can facilitate such change by
      generating movement through the introduction of small focused projects that meet
      the stakeholders' needs, by creating conditions for interaction and sense making,
      and by promoting the new desired cultural values.

PMID- 25070015
TI  - Usefulness of a new gelatin glue sealant system for dural closure in a rat
      durotomy model.
AB  - Watertight dural closure is imperative after neurosurgical procedures, because
      inadequately treated leakage of cerebrospinal fluid (CSF) can have serious
      consequences. We used a rat durotomy model to test the usefulness of a new
      gelatin glue as a dural sealant in a rat model of transdural CSF leakage. All
      rats were randomly divided into one of the following three treatment groups: no
      application (control group: N = 18), application of fibrin glue (fibrin glue
      group: N = 18), and application of the new gelatin glue (new gelatin glue group:
      N = 18). The craniotomy side was re-opened, and CSF leakage was checked and
      recorded at 1, 7, and 28 days postoperatively. The new gelatin glue was adequate
      for stopping CSF leakage; no leakage was observed at postoperative days 1 or 7,
      and leakage was observed in only one rat at postoperative day 28. This result was
      statistically significant when compared to the control group (P = 0.002, P =
      0.015, P = 0.015, respectively). The pathologic score of the new gelatin group
      was not different from that of the control or fibrin glue groups. We conclude
      that our new gelatin glue provides effective watertight closure 1, 7, and 28 days
      after operation in the rat durotomy model. 

PMID- 25070016
TI  - Adult growth hormone deficiency: current concepts.
AB  - The clinical syndrome of adult growth hormone deficiency (AGHD) was widely
      recognized in the 1980s. In this review, we first describe the clinical features
      and diagnosis of AGHD and then state the effects of growth hormone (GH) therapy
      for these patients. The main characteristics of AGHD are abnormal body
      composition, dyslipidemia, insulin resistance, and an impaired quality of life
      (QoL) due to decreased psychological well-being. For diagnosing AGHD, the
      international consensus guidelines have suggested that an insulin tolerance test
      (ITT) is the gold standard, but in Japan, the growth hormone releasing peptide-2
      (GHRP-2) test is available and is recommended as a convenient and safe GH
      stimulating test. The cut-off for diagnosing severe AGHD is a peak GH
      concentration of 9 g/L during the GHRP-2 test. Since 2006, GH therapy has been
      approved for Japanese patients with severe AGHD. For adults, GH replacement
      therapy should be initiated at a low dose (3 g/kg body weight/day), followed by
      individualized dose titration while monitoring patients' clinical status and
      serum insulin-like growth factor-I (IGF-I) concentrations. A variety of favorable
      effects of GH replacement have been indicated; however, it has not yet been
      established fully whether there is a direct effect of GH treatment on reducing
      mortality. 

PMID- 25070017
TI  - Usefulness of intraoperative monitoring of visual evoked potentials in
      transsphenoidal surgery.
AB  - Postoperative visual outcome is a major concern in transsphenoidal surgery (TSS).
      Intraoperative visual evoked potential (VEP) monitoring has been reported to have
      little usefulness in predicting postoperative visual outcome. To re-evaluate its
      usefulness, we adapted a high-power light-stimulating device with
      electroretinography (ERG) to ascertain retinal light stimulation. Intraoperative
      VEP monitoring was conducted in TSSs in 33 consecutive patients with sellar and
      parasellar tumors under total venous anesthesia. The detectability rates of N75,
      P100, and N135 were 94.0%, 85.0%, and 79.0%, respectively. The mean latencies and
      amplitudes of N75, P100, and N135 were 76.8 +/- 6.4 msec and 4.6 +/- 1.8 MUV,
      98.0 +/- 8.6 msec and 5.0 +/- 3.4 MUV, and 122.1 +/- 16.3 msec and 5.7 +/- 2.8
      MUV, respectively. The amplitude was defined as the voltage difference from N75
      to P100 or P100 to N135. The criterion for amplitude changes was defined as a >
      50% increase or 50% decrease in amplitude compared to the control level. The
      surgeon was immediately alerted when the VEP changed beyond these thresholds, and
      the surgical manipulations were stopped until the VEP recovered. Among the 28
      cases with evaluable VEP recordings, the VEP amplitudes were stable in 23 cases
      and transiently decreased in 4 cases. In these 4 cases, no postoperative vision
      deterioration was observed. One patient, whose VEP amplitude decreased without
      subsequent recovery, developed vision deterioration. Intraoperative VEP
      monitoring with ERG to ascertain retinal light stimulation by the new stimulus
      device was reliable and feasible in preserving visual function in patients
      undergoing TSS. 

PMID- 25070018
TI  - A modified combined transseptal/transnasal binostril approach for pituitary
      lesions in patients with a narrow nasal space: technical note.
AB  - We describe a modification of the combined transseptal/transnasal binostril
      approach using a two-surgeon, four-handed technique (modified Stamm's approach)
      for pituitary lesions in patients with narrow nasal spaces. This approach
      comprises of a transseptal route through one nostril and a transnasal route
      without harvesting a pedicled nasoseptal flap (NSF) through the other. On the
      transseptal side, the nasal septum was removed using an endoscopic septoplasty
      technique. On the transnasal side, the mucosa containing the septal branch of the
      sphenopalatine artery over the face of the sphenoid and nasal septum was
      preserved for harvesting the NSF if an intraoperative cerebrospinal fluid leak
      was encountered. This approach was performed in six patients with pituitary
      lesions, including four non-functioning macroadenomas, one growth hormone
      producing macroadenoma, and one Rathke's cleft cyst, all of which were associated
      with a severe deviation of the nasal septum and/or narrow nasal space. The
      meticulous and comfortable manipulation of an endoscope and instruments were
      achieved in all six patients without surgical complications. Our findings,
      although obtained in a limited number of cases, suggest that the modified Stamm's
      approach may be useful for selected patients, particularly those with a severe
      deviation of the nasal septum, without considerable damage to the nasal passages.

PMID- 25070020
TI  - Fetal beat detection in abdominal ECG recordings: global and time adaptive
      approaches.
AB  - We present a method for location of fetal QRS in maternal abdominal ECG
      recordings. This method's initial, global approach was proposed in the context of
      the 2013 PhysioNet/Computing in Cardiology Challenge where it was tested on the
      447 four channel one-minute recordings.The first step is filtering to eliminate
      baseline wander and high frequency noise. Upon detection, maternal QRS is removed
      on each channel using a filter applied to the other three channels. Next we
      locate fetal QRS on each channel and select the channel with the best set of
      detections. The method was awarded the third-best score in the Challenge event 1
      with 278.755 (beats/minute) and the fourth-best score on event 2 with 28.201
      ms.The 5 min long recordings of the Abdominal and Direct Fetal ECG Database were
      used to further test the method. This database contains five recordings obtained
      from women in labor. Results in these longer recordings were not satisfactory.
      This appears to be particularly the case in recordings with a more clearly non
      stationary nature. In a new approach to our method, some changes are introduced.
      Two features are updated over time: the filter used to eliminate maternal QRS and
      the channel used to detect fetal beats. These changes significantly improved the
      QRS detection performance on longer recordings, but the scores on the 1 minute
      Challenge recordings were degraded.

PMID- 25070019
TI  - Modified hemostatic technique using microfibrillar collagen hemostat in
      endoscopic endonasal transsphenoidal surgery: technical note.
AB  - Microfibrillar collagen hemostat (MCH) is accepted as an effective topical
      hemostatic agent during endoscopic endonasal transsphenoidal surgery (EETS),
      particularly to achieve venous hemostasis; however, handling MCH may be
      troublesome because of its adherence to gloves and instruments. We describe here
      a method of "injection" of MCH suspension using a syringe applicator. This
      technique allows a rapid and precise delivery of MCH to the bleeding points and
      thereby results in effective hemostasis; in addition, it is easy to prepare and
      it is also inexpensive. 

PMID- 25070021
TI  - Automatic modeling of pectus excavatum corrective prosthesis using artificial
      neural networks.
AB  - Pectus excavatum is the most common deformity of the thorax. Pre-operative
      diagnosis usually includes Computed Tomography (CT) to successfully employ a
      thoracic prosthesis for anterior chest wall remodeling. Aiming at the elimination
      of radiation exposure, this paper presents a novel methodology for the
      replacement of CT by a 3D laser scanner (radiation-free) for prosthesis modeling.
      The complete elimination of CT is based on an accurate determination of ribs
      position and prosthesis placement region through skin surface points. The
      developed solution resorts to a normalized and combined outcome of an artificial
      neural network (ANN) set. Each ANN model was trained with data vectors from 165
      male patients and using soft tissue thicknesses (STT) comprising information from
      the skin and rib cage (automatically determined by image processing algorithms).
      Tests revealed that ribs position for prosthesis placement and modeling can be
      estimated with an average error of 5.0 +/- 3.6mm. One also showed that the ANN
      performance can be improved by introducing a manually determined initial STT
      value in the ANN normalization procedure (average error of 2.82 +/- 0.76 mm).
      Such error range is well below current prosthesis manual modeling (approximately
      11 mm), which can provide a valuable and radiation-free procedure for prosthesis
      personalization.

PMID- 25070022
TI  - Predicting flow in aortic dissection: comparison of computational model with PC
      MRI velocity measurements.
AB  - Aortic dissection is a life-threatening process in which the weakened wall
      develops a tear, causing separation of wall layers. The dissected layers separate
      the original true aortic lumen and a newly created false lumen. If untreated, the
      condition can be fatal. Flow rate in the false lumen is a key feature for false
      lumen patency, which has been regarded as one of the most important predictors of
      adverse early and later outcomes. Detailed flow analysis in the dissected aorta
      may assist vascular surgeons in making treatment decisions, but computational
      models to simulate flow in aortic dissections often involve several assumptions.
      The purpose of this study is to assess the computational models adopted in
      previous studies by comparison with in vivo velocity data obtained by means of
      phase-contrast magnetic resonance imaging (PC-MRI). Aortic dissection geometry
      was reconstructed from computed tomography (CT) images, while PC-MRI velocity
      data were used to define inflow conditions and to provide distal velocity
      components for comparison with the simulation results. The computational fluid
      dynamics (CFD) simulation incorporated a laminar-turbulent transition model,
      which is necessary for adequate flow simulation in aortic conditions. Velocity
      contours from PC-MRI and CFD in the two lumens at the distal plane were compared
      at four representative time points in the pulse cycle. The computational model
      successfully captured the complex regions of flow reversal and recirculation
      qualitatively, although quantitative differences exist. With a rigid wall
      assumption and exclusion of arch branches, the CFD model over-predicted the false
      lumen flow rate by 25% at peak systole. Nevertheless, an overall good agreement
      was achieved, confirming the physiological relevance and validity of the
      computational model for type B aortic dissection with a relatively stiff
      dissection flap. 

PMID- 25070023
TI  - Interactions among nitrogen fixation and soil phosphorus acquisition strategies
      in lowland tropical rain forests.
AB  - Paradoxically, symbiotic dinitrogen (N2 ) fixers are abundant in nitrogen (N)
      rich, phosphorus (P)-poor lowland tropical rain forests. One hypothesis to
      explain this pattern states that N2 fixers have an advantage in acquiring soil P
      by producing more N-rich enzymes (phosphatases) that mineralise organic P than
      non-N2 fixers. We assessed soil and root phosphatase activity between fixers and
      non-fixers in two lowland tropical rain forest sites, but also addressed the
      hypothesis that arbuscular mycorrhizal (AM) colonisation (another P acquisition
      strategy) is greater on fixers than non-fixers. Root phosphatase activity and AM
      colonisation were higher for fixers than non-fixers, and strong correlations
      between AM colonisation and N2 fixation at both sites suggest that the N-P
      interactions mediated by fixers may generally apply across tropical forests. We
      suggest that phosphatase enzymes and AM fungi enhance the capacity of N2 fixers
      to acquire soil P, thus contributing to their high abundance in tropical forests.

PMID- 25070024
TI  - Esophageal carcinoma cell line with high EGFR polysomy is responsive to
      gefitinib.
AB  - PURPOSE: It has previously been shown that gefitinib-treated patients with
      epidermal growth factor receptor (EGFR) gene amplification or high polysomy had a
      statistically significant improvement in response, time to progression, and
      survival in non-small cell lung cancer (NSCLC). Only few studies utilizing anti
      EGFR treatment in advanced esophageal adenocarcinomas have been performed and the
      results have been heterogeneous. The aim of this study was to evaluate EGFR
      targeted therapy with gefitinib in esophageal adenocarcinoma with a high EGFR
      polysomy. METHODS: Novel esophageal cell lines PT6216 and LN6216c were
      established from primary tumor and lymph node metastasis of a patient with highly
      aggressive and metastatic adenocarcinoma. Pathological examination including
      tumor differentiation and prognostic marker analysis, immunohistochemical EGFR
      expression analysis, EGFR fluorescence in situ hybridization, and mutation
      analysis were performed. Response of novel cell lines to gefitinib treatment was
      evaluated by cell proliferation and vitality assays. Fifty-four esophageal
      adenocarcinoma specimens were evaluated for EGFR gene copy gain. RESULTS: The
      primary tumor cell line PT6216 and the lymph node cell line LN6216c show a
      homogenously high polysomy for EGFR determined by FISH analysis. Cell
      proliferation and vitality are highly sensitive to the tyrosine kinase inhibitor
      gefitinib compared to esophageal control cells without a high polysomy for EGFR.
      High polysomy for EGFR was found in 35 % of patients. CONCLUSION: We show for the
      first time a significant treatment response to the EGFR tyrosine kinase inhibitor
      gefitinib in esophageal tumor cells with a high polysomy for EGFR, suggesting a
      future role of anti-EGFR therapy for esophageal adenocarcinoma patients with a
      high EGFR polysomy.

PMID- 25070027
TI  - The human skin microbiome.

PMID- 25070026
TI  - Effectiveness of a sediment time critical removal action-PCB reduction in fish
      tissue, surface water, and sediment via wet excavation.
AB  - Documenting successful remediation of polychlorinated biphenyl (PCB)-contaminated
      sediments is limited; potentially due to inadequate monitoring methods,
      complexities associated with the environment, and selected remedial techniques.
      At some sites, absence of appropriate baseline and postremoval monitoring limits
      proper evaluation of remedial efficacy. Accurate interpretation of interactions
      between media, space, time, species, lipid content, and remedial technique
      requires robust study design and data. This article presents baseline and
      postremoval data documenting reduced PCB concentrations in fish tissue, surface
      water, and sediment in response to the US Environmental Protection Agency (USEPA)
      time-critical removal action (TCRA) that was conducted at the former Bryant Mill
      Pond (BMP) on Portage Creek in Kalamazoo, Michigan. The BMP is part of an
      operable unit (OU) within the Allied Paper, Inc./Portage Creek/Kalamazoo River
      Superfund Site. PCBs discharged to the creek as a byproduct of carbonless copy
      paper recycling are the primary contaminant of concern. Paper waste residuals
      commonly appear as gray to light gray clays in river sediments and floodplain
      soils. The cleanup criterion was 10 mg/kg, with a residual PCB concentration goal
      of 1 mg/kg. Because the PCB-containing waste is (generally) associated with
      readily visible light gray clay, excavation of all visibly contaminated current
      or formerly impounded sediment served as a surrogate for the cleanup criteria and
      goal. Sediment was wet excavated and backfilled after diversion of the creek.
      After confirmation that PCB concentrations met cleanup criteria, the stream was
      diverted to the excavated side, and excavation and backfilling were completed.
      Overall, 146000 cubic yards of material including PCB-contaminated sediments were
      removed from the BMP. The long-term monitoring (LTM) program implemented by the
      Michigan Department of Environmental Quality (MDEQ), and historic data from a
      variety of sources (federal, state, and local agencies and responsible parties)
      provided data demonstrating TCRA effectiveness. Before TCRA, surface sediment PCB
      concentration in instream and formerly inundated sediment combined was 83 mg/kg
      (with a maximum of 700 mg/kg). Instream sediments that are more representative of
      fish exposures had a pre-TCRA surface weighted average concentration (SWAC) of 27
      mg/kg. The post-TCRA SWAC for instream and floodplain sediments combined was 0.26
      mg/kg. Average surface water concentrations at the downstream end of the BMP were
      reduced from 0.11 ug/L pre-TCRA to 0.0025 ug/L post-TCRA. Tissue samples for
      adult carp fillets decreased from 4 mg/kg pre-TCRA to 0.26 mg/kg post-TCRA; whole
      body white suckers from 3 mg/kg pre-TCRA to 0.1 mg/kg post-TCRA; whole body
      channel catfish from 39 mg/kg-L pre-TCRA to 2.6 mg/kg-L post-TCRA. Concentrations
      of PCBs in 2 species of resident fish (carp and white suckers), caged channel
      catfish, surface water, and sediment were reduced by over 1 order of magnitude
      within 1 year of completion, substantively accelerating natural recovery
      processes. A slight increase in PCB concentration was observed in both whole body
      suckers and adult carp fillets in the second monitoring period post-TCRA;
      however, these concentrations are still near an order of magnitude less than pre
      TCRA concentrations and appear to be currently stable or on a slight downward
      trend.

PMID- 25070025
TI  - Development of kit formulations for (99m) TcN-MPO: a cationic radiotracer for
      myocardial perfusion imaging.
AB  - The objective of this study was to develop a kit formulation for [(99m)
      TcN(mpo)(PNP5)](+) (MPO = 2-mercaptopyridine oxide), ((99m) TcN-MPO) to support
      its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were
      performed using three different formulations (two-vial formulation and single
      vial formulations with/without SnCl2 ) to explore the factors influencing
      radiochemical purity (RCP) of (99m) TcN-MPO. We found that the most important
      factor affecting the RCP of (99m) TcN-MPO was the purity of PNP5. (99m) TcN-MPO
      was prepared >98% RCP (n = 20) using the two-vial formulation. For single-vial
      formulations with/without SnCl2 , beta-cyclodextrin (beta-CD) is particularly
      useful as a stabilizer for PNP5. The RCP of (99m) TcN-MPO was 95-98% using beta
      CD, but its RCP was only 90-93% with gamma-cyclodextrin (gamma-CD). It seems that
      PNP5 fits better into the inner cavity of beta-CD, which forms more stable
      inclusion complex than gamma-CD in the single-vial formulations. The results from
      biodistribution and imaging studies in Sprague-Dawley rats clearly demonstrated
      biological equivalence of three different formulations. Single photon-emission
      computed tomography data suggested that high quality images could be obtained at
      0-30-min post-injection without significant interference from the liver
      radioactivity. Considering the ease for (99m) Tc-labeling and high RCP of (99m)
      TcN-MPO, the non-SnCl2 single-vial formulation is an attractive choice for future
      clinical studies. 

PMID- 25070028
TI  - Suture anchor fixation for scaphoid nonunions with small proximal fragments:
      report of 11 cases.
AB  - PURPOSE: To describe the use of 2 suture anchors as the fixation devices in the
      management of 11 patients with scaphoid proximal pole nonunions with small
      proximal fragments. METHODS: In a prospective study, 11 patients with proximal
      pole scaphoid nonunions (10 with small proximal fragments and 1 with an oblique
      nonunion line) were evaluated before surgery by standard wrist x-rays and
      functional wrist scores including a visual analog scale (VAS), Mayo wrist score,
      and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH). The nonunion
      site was fixed with 2 suture anchors supplemented with autologous cancellous bone
      graft. Postoperative evaluations consisting of functional wrist scores and
      evaluation of radiological union were performed 9 months after surgery. RESULTS:
      At the end of the study, we observed union in 10 of the 11 patients. The
      QuickDASH and VAS scores showed significant improvement, and 10 patients had
      satisfactory Mayo scores. CONCLUSIONS: We propose the technique of suture anchor
      fixation for cases of proximal scaphoid nonunion in which secure internal
      fixation with common techniques is challenging because of the small size of the
      proximal fragment and the obliquity of the nonunion site. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 25070029
TI  - Commentary on "Comparison of compression screw and perpendicular clamp in ulnar
      shortening osteotomy".

PMID- 25070030
TI  - Surgical techniques of olecranon fractures.
AB  - Olecranon fractures are common upper extremity injuries. The vast majority are
      treated with operative fixation. Many treatment techniques have been described
      including tension band and plating. This review covers the most commonly used
      fixation techniques in detail, including pearls and pitfalls with case examples
      of both successful treatments and potential complications. 

PMID- 25070031
TI  - Aquatic hand injuries.

PMID- 25070033
TI  - Chronic hand infections.
AB  - Chronic infections of the hand are uncommon, and a high index of suspension is
      required for their early diagnosis. These can be grouped based on the
      microorganism. Mycobacterial infections include tuberculosis, atypical
      mycobacterial infections, and leprosy. Other bacterial infections include
      actinomycosis, cat-scratch disease, syphilis, tularemia, bacillary angiomatosis,
      and actinomycetoma. Fungal infections may be classified as cutaneous (affecting
      the skin, the paronychia or nail plate), subcutaneous (mainly lymphocutaneous
      sporotrichosis and dermatiaceous infections), and deep fungal infections. Each
      type of deep fungal infection has a "classic" presentation and this is
      emphasized. Finally, common chronic viral infections of the hand include warts
      and orf. 

PMID- 25070032
TI  - Acute hand infections.
AB  - The continued emergence of antibiotic-resistant bacteria and the development of
      only a few new classes of antibiotics over the past 50 years have made the
      treatment of acute hand infections problematic. Prompt diagnosis and treatment
      are important, because hand stiffness, contractures, and even amputation can
      result from missed diagnoses or delayed treatment. The most common site of hand
      infections is subcutaneous tissue and the most common mechanism is trauma. An
      immunocompromised state, intravenous drug abuse, diabetes mellitus, and steroid
      use all predispose to infections. 

PMID- 25070034
TI  - Southern California Society for Surgery of the Hand Award for the Journal of Hand
      Surgery 2013 article of the year.

PMID- 25070036
TI  - Evaluation of a parent-designed programme to support tooth brushing of infants
      and young children.
AB  - OBJECTIVES: This study developed and tested an intervention to help parents
      establish a routine of brushing their young children's teeth twice a day.
      METHODS: Community-based participatory research methods were used to engage
      parents in the design of the intervention to maximize its relevance and
      acceptability to others. Input was obtained by interviews and focus groups. The
      resulting intervention was four 90-min small-group sessions that provided
      educational information, direct instruction, practice and peer-to-peer problem
      solving. A pre- to post-non-randomized design was used to evaluate the
      intervention's effect to increase or maintain parents' twice daily brushing.
      RESULTS: Intervention participants were 67 primary caregivers of children under
      six years of age. Of the 67 initial participants, 50 completed a post
      intervention questionnaire administered 4 to 8 weeks following the intervention.
      The proportion of parents who reported brushing their young children's teeth
      twice a day increased significantly from 59 per cent prior to the intervention to
      89 per cent post-intervention (McNemar's X(2)  = 10.71, P = 0.002). There were
      concomitant and statistically significant increases over the study period in
      parents' confidence for brushing twice a day, attitudes about the importance of
      brushing and their self-efficacy for tooth brushing. Parents' knowledge of
      children's oral health, assessed by a 15-item scale developed for this study
      ('Things to Know About Baby Teeth'), also increased significantly. CONCLUSIONS:
      Twice daily tooth brushing is a low-cost, effective strategy to reduce the risk
      of childhood caries. As demonstrated here, community-based efforts can help
      parents achieve this important health behaviour.

PMID- 25070035
TI  - Effective inhibition of melanoma tumorigenesis and growth via a new complex
      vaccine based on NY-ESO-1-alum-polysaccharide-HH2.
AB  - BACKGROUND: A safe and effective adjuvant plays an important role in the
      development of a vaccine. However, adjuvants licensed for administration in
      humans remain limited. Here, for the first time, we developed a novel combination
      adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities,
      consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic
      innate defense regulator peptide HH2. METHODS: The adjuvant effects of APH were
      examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic
      models. We further determined the immunogenicity and anti-tumor effect of NY-ESO
      1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude
      mice. Cell-mediated and antibody-mediated immune responses were evaluated.
      RESULTS: The APH complex significantly promoted antigen uptake, maturation and
      cross-presentation of dendritic cells and enhanced the secretion of TNF-alpha,
      MCP-1 and IFN-gamma by human peripheral blood mononuclear cells compared with
      individual components. Vaccination of NAPH resulted in significant tumor
      regression or delayed tumor progression in prophylactic and therapeutic models.
      In addition, passive serum/cellular therapy potently inhibited tumor growth of NY
      ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and
      greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH
      vaccination effectively stimulated innate immunity, and boosted both arms of the
      adaptive humoral and cellular immune responses to suppress tumorigenesis and
      growth of melanoma. CONCLUSIONS: Our study revealed the potential application of
      APH complex as a novel immunomodulatory agent for vaccines against tumor
      refractory and growth.

PMID- 25070037
TI  - Rapid corticosteroid tapering: Important risk factor for type 1 autoimmune
      hepatitis relapse in Japan.
AB  - AIM: Patients with autoimmune hepatitis (AIH) sometimes relapse after
      immunosuppressive therapies are discontinued or sometimes even while they are
      still being administrated. Furthermore, relapse often occurs in the absence of
      AIH relapse risk factors. This study aimed to identify the frequency of relapse
      and to analyze the risk factors associated with relapse in type 1 AIH patients.
      METHODS: Clinical characteristics and therapeutic processes were assessed in 129
      type 1 AIH patients. RESULTS: Relapse was identified in 39 (30.2%) type 1 AIH
      patients after alanine aminotransferase (ALT) level normalization. ALT levels
      significantly increased when corticosteroid treatment was initiated in relapsed
      patients compared with that in patients with sustained remission. The reduction
      dose and rate of corticosteroid taper were significantly increased in relapsed
      patients compared with those in sustained remission patients. Moreover, positive
      correlations were identified between the reduction dose/taper rate and initial
      corticosteroid dose, and ALT levels, total bilirubin levels and hepatitis
      activity. Multivariate logistic regression analysis identified the corticosteroid
      reduction rate as significantly associated with AIH relapse. CONCLUSION:
      Corticosteroid reduction taper rate until ALT normalization is an important AIH
      relapse risk factor.

PMID- 25070038
TI  - Quantum study of boron nitride nanotubes functionalized with anticancer
      molecules.
AB  - Full DFT-D2 calculations were carried out to study the interactions between
      single wall (10,10) boron nitride nanotubes (BNNTs) and different molecules, such
      as azomethine (C2H5N) and an anticancer agent (Pt(IV) complex) linked to an amino
      derivative chain. The geometry of the (10,10) BNNT-azomethine and the BNNT-amino
      derivative system was optimised by considering different molecular configurations
      on the inner and outer surfaces of the nanotube. Simulation results showed that
      the most stable physisorption state for both molecules was located inside the
      nanotube in a parallel configuration. We showed also that the molecular
      chemisorption was possible only when the azomethine was present above two
      adjacent B and N atoms of a hexagon. The attachment of an azomethine plus a
      subsequent drug did not perturb the cycloaddition process. Moreover, all
      theoretical results showed that the therapeutic agent complex was not affected
      when it was attached onto BNNTs.

PMID- 25070040
TI  - Inhibition of HDAC increases the senescence induced by natural polyphenols in
      glioma cells.
AB  - Cellular senescence is an irreversible block of cellular division, and induction
      of senescence is being considered for treatment of many cancer types, mainly
      those resistant to classical pro-apoptotic therapies. Resveratrol (Rsv) and
      quercetin (Quer), two natural polyphenols, are able to induce senescence in
      different cancer models, including gliomas, the most common and aggressive
      primary brain tumor. These polyphenols modulate the activity of several proteins
      involved in cell growth and death in cancer cells, including histone deacetylases
      (HDAC), but the role of HDAC in senescence induced by Rsv and Quer is unclear.
      The HDAC inhibitor sodium butyrate (NaB) potentiated the pro-senescent effect of
      Rsv and Quer in human and rat glioma cell lines but not in normal rat astrocytes.
      Furthermore, the increment of Quer-induced senescence by NaB was accompanied by
      an increase of reactive oxygen species levels and an increment of the number of
      cells with nuclear abnormalities. Altogether, these data support a positive role
      of HDAC inhibition on the senescence induced by these polyphenols, and therefore
      co-treatment of HDAC inhibitors and polyphenols emerges as a potential
      alternative for gliomas. 

PMID- 25070039
TI  - Identification and functional analysis of AG1-IA specific genes of Rhizoctonia
      solani.
AB  - Rhizoctonia solani is an important necrotrophic fungal pathogen which causes
      disease on diverse plant species. It has been classified into 14 genetically
      distinct anastomosis groups (AGs), however, very little is known about their
      genomic diversity. AG1-IA causes sheath blight disease in rice and controlling
      this disease remains a challenge for sustainable rice cultivation. Recently the
      draft genome sequences of AG1-IA (rice isolate) and AG1-IB (lettuce isolate) had
      become publicly available. In this study, using comparative genomics, we report
      identification of 3,942 R. solani genes that are uniquely present in AG1-IA. Many
      of these genes encode important biological, molecular functions and exhibit
      dynamic expression during in-planta growth of the pathogen in rice. Based upon
      sequence similarity with genes that are required for plant and human/zoonotic
      diseases, we identified several putative virulence/pathogenicity determinants
      amongst AG1-IA specific genes. While studying the expression of 19 randomly
      selected genes, we identified three genes highly up-regulated during in-planta
      growth. The detailed in silico characterization of these genes and extent of
      their up-regulation in different rice genotypes, having variable degree of
      disease susceptibility, suggests their importance in rice-Rhizoctonia
      interactions. In summary, the present study reports identification, functional
      characterization of AG1-IA specific genes and predicts important virulence
      determinants that might enable the pathogen to grow inside hostile plant
      environment. Further characterization of these genes would shed useful insights
      about the pathogenicity mechanism of AG1-IA on rice.

PMID- 25070041
TI  - Screening and confirmation of myo-inositol trispyrophosphate (ITPP) in human
      urine by hydrophilic interaction liquid chromatography high resolution / high
      accuracy mass spectrometry for doping control purposes.
AB  - Myo-inositol trispyrophosphate (ITPP) is a novel allosteric effector of
      haemoglobin with high permeation selectivity across the red blood cell plasma
      membrane. Due to its potential to reduce the oxygen affinity of haemoglobin, ITPP
      application results in an enhanced oxygen release in hypoxic tissues. Therefore,
      ITPP is being examined for the treatment of numerous illnesses that involve
      hypoxia, such as cardiovascular diseases, cancer or Alzheimer's disease. Similar
      to the prohibited substance Efaproxiral(r), ITPP increases maximal exercise
      capacity in mice, providing high potential to be misused in sports. To keep up
      with cheating athletes, a fast and reliable liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for screening and confirmation of ITPP in human
      urine for doping control purposes was developed. According to the molecule's
      distinct hydrophilic properties, extraction from complex biological matrices is
      challenging and conventional reversed phase liquid chromatography (RPLC)
      separations are not suitable for its detection. Therefore an approach based on
      hydrophilic interaction liquid chromatography (HILIC) Orbitrap mass spectrometry
      was established. The methodology was fully validated for qualitative purposes.
      Screening and confirmation assay are characterized by satisfactory specificity
      and robustness, adequate intra-day (screening: 4.9-8.1%; confirmation: 2.0-6.7%)
      and inter-day precision (screening: 4.6-9.1%; confirmation: 1.8-6.6%), excellent
      linear correlations (>0.99) with sufficient LLOD in the sub ng/mL range
      (screening: 15 ng/mL; confirmation: 1 ng/mL). In addition it could be shown that
      ITPP is stable in human urine under the mandatory storage period and conditions
      for doping control laboratories. To our knowledge, this is the first validated
      'dilute-and-inject' LC-MS/MS method for the reliable detection of ITPP in human
      urine.

PMID- 25070042
TI  - Pituitary side effects of old and new drugs.
AB  - INTRODUCTION: Pituitary function is influenced by several drugs, including anti
      depressant, opioids, glucocorticoids, chemotherapeutic agents, immunomodulators
      and the newly developed tyrosine kinase inhibitors. In most instances, treatment
      with these drugs negatively affects pituitary function, but in rare cases an
      activation of specific hypothalamic-pituitary axes may be observed. Several of
      the observed pituitary side effects are reversible after drug withdrawal, but
      pituitary function deficiency may persist long-term. In addition to the well
      known drugs, recent evidence shows that also non-steroidal anti-inflammatory
      drugs impair gonadal axis at pituitary level, while antipsychotic phenothiazines
      alter TSH response to TRH and TSH levels. Atypical antipsychotics may decrease
      TRH-stimulated TSH. Tricyclic antidepressant drugs interfere with the hypothalamo
      pituitary-thyroid axis by decreasing TSH response to TRH. Anabolic-androgenic
      steroids, marijuana, cocaine, methamphetamines, and opioid narcotics negatively
      impact fertility, also acting at hypothalamic-pituitary level. CONCLUSIONS: Many
      of the drugs administered routinely in the intensive care unit significantly
      impact the hypothalamic-pituitary axis. Therefore, an increased awareness on
      pituitary side effects of drugs commonly used in clinical practice is necessary
      in order to rule out possible pharmacological interference when assessing
      patients with pituitary deficiencies.

PMID- 25070043
TI  - Detection of metastases from differentiated thyroid cancer by different imaging
      techniques (neck ultrasound, computed tomography and [18F]-FDG positron emission
      tomography) in patients with negative post-therapeutic 131I whole-body scan and
      detectable serum thyroglobulin levels.
AB  - INTRODUCTION: DTC patients having detectable Tg and negative post-therapeutic
      (131)I-WBS have to be investigated by different imaging techniques to detect
      metastases. PURPOSE: Comparison of neck US, CT and [18F]-FDG PET scan. METHODS:
      In 49 DTC patients with biochemical disease, neck was examined by US, CT and
      [18F]-FDG PET. FNA was performed and Tg was determined by FNA-Tg in selected
      cases of suspicious lymph nodes. Thorax was examined by CT and PET. Serum Tg was
      measured on LT4 therapy (basal Tg) and after the stimulation with recombinant
      human TSH (peak Tg). RESULTS: A thyroid remnant was seen by US, CT and PET in
      eight patients; recurrences were seen by US, CT and PET in six, five and five
      patients, respectively. Two metastatic nodes were identified by US and CT but not
      by PET. Lung micronodules were detected by CT in 7/49 (14.3 %) patients and by
      FDG PET in three of them. Basal Tg ranged from 0.5-1,725 ng/ml while peak Tg
      ranged from 0.5 to 2,135 ng/ml: the distribution between positive and negative
      patients was similar. Bone scan was negative in all cases. CONCLUSIONS: In DTC
      patients with detectable Tg and negative I-131 post-therapy WBS, imaging
      examination revealed remnant or metastases in 43 % of cases. Remnant and
      recurrences were equally detected by the three techniques; US was better than
      [18F]-FDG PET for lymph node metastases since this latter method can give false
      both positive and negative results; chest examination is best made by CT versus
      FDG PET due to its higher spatial resolution.

PMID- 25070045
TI  - Orbital occupancy and charge doping in iron-based superconductors.
AB  - The intrinsic Fe local magnetic moment and Fe orbital occupations of iron-based
      superconductors are unveiled through the local, real-space capability of
      aberration-corrected scanning transmission electron microscopy/electron energy
      loss spectroscopy (STEM/EELS). Although the ordering of Fe moments needs to be
      suppressed for superconductivity to arise, the local, fluctuating Fe magnetic
      moment is enhanced near optimal superconductivity. 

PMID- 25070046
TI  - Treatment monitoring of topical ingenol mebutate in actinic keratoses with the
      combination of optical coherence tomography and reflectance confocal microscopy:
      a case series.

PMID- 25070044
TI  - Anterior pituitary autoantibodies in patients with type 1 diabetes mellitus:
      methodological problems and clinical correlations.
AB  - BACKGROUND: Anti-pituitary antibodies (APA) were described in patients with Type
      1 Diabetes (T1D) but their prevalence and relevance remain controversial.
      MATERIALS AND METHODS: We evaluated the APA prevalence in Sardinian sera from 100
      T1D patients, 70 Type 2 Diabetes (T2D) patients and 62 healthy controls, using
      indirect immunofluorescence on bovine pituitary sections. To compare two
      different substrates, we tested using bovine sections, further T1D patient sera
      (n = 11, from Pisa) previously analysed for APA on monkey sections, while some
      T1D Sardinian patient sera (n = 22) were tested on monkey sections. According to
      preliminary experiments, positivity were considered >=1:200 and >=1:20 for bovine
      and monkey substrates, respectively. RESULTS AND DISCUSSION: Using bovine
      sections, APA were detected in 7/100 Sardinian T1D patients (at 1:200 titer) and
      in none of the other Sardinian sera tested. When the T1D sera from Pisa were
      tested on bovine and the T1D Sardinian sera were tested on monkey, none of these
      sera showed corresponding positivity for APA. Pituitary hormone dysfunctions were
      not found in the 7 APA-positive Sardinian T1D patients. The present study shows
      that the presence of APA at low-titer is highly related to T1D but not associated
      with any pituitary dysfunction while the animal species used as substrate appears
      crucial. CONCLUSION: Further studies are needed to ascertain whether APA detected
      by different animal species may have different pathological relevance in T1D
      and/or whether APA in the long run may predict future anterior pituitary
      dysfunction.

PMID- 25070047
TI  - A continuous optimization approach for inferring parameters in mathematical
      models of regulatory networks.
AB  - BACKGROUND: The advances of systems biology have raised a large number of
      sophisticated mathematical models for describing the dynamic property of complex
      biological systems. One of the major steps in developing mathematical models is
      to estimate unknown parameters of the model based on experimentally measured
      quantities. However, experimental conditions limit the amount of data that is
      available for mathematical modelling. The number of unknown parameters in
      mathematical models may be larger than the number of observation data. The
      imbalance between the number of experimental data and number of unknown
      parameters makes reverse-engineering problems particularly challenging. RESULTS:
      To address the issue of inadequate experimental data, we propose a continuous
      optimization approach for making reliable inference of model parameters. This
      approach first uses a spline interpolation to generate continuous functions of
      system dynamics as well as the first and second order derivatives of continuous
      functions. The expanded dataset is the basis to infer unknown model parameters
      using various continuous optimization criteria, including the error of simulation
      only, error of both simulation and the first derivative, or error of simulation
      as well as the first and second derivatives. We use three case studies to
      demonstrate the accuracy and reliability of the proposed new approach. Compared
      with the corresponding discrete criteria using experimental data at the
      measurement time points only, numerical results of the ERK kinase activation
      module show that the continuous absolute-error criteria using both function and
      high order derivatives generate estimates with better accuracy. This result is
      also supported by the second and third case studies for the G1/S transition
      network and the MAP kinase pathway, respectively. This suggests that the
      continuous absolute-error criteria lead to more accurate estimates than the
      corresponding discrete criteria. We also study the robustness property of these
      three models to examine the reliability of estimates. Simulation results show
      that the models with estimated parameters using continuous fitness functions have
      better robustness properties than those using the corresponding discrete fitness
      functions. CONCLUSIONS: The inference studies and robustness analysis suggest
      that the proposed continuous optimization criteria are effective and robust for
      estimating unknown parameters in mathematical models.

PMID- 25070048
TI  - Evaluation of the protective potential of brain microvascular endothelial cell
      autophagy on blood-brain barrier integrity during experimental cerebral ischemia
      reperfusion injury.
AB  - Brain microvascular endothelial cell (BMVEC) injury induced by ischemia
      reperfusion (I/R) is the initial phase of blood-brain barrier (BBB) disruption,
      which results in a poor prognosis for ischemic stroke patients. Autophagy occurs
      in ischemic brain and has been shown to exhibit protective effects on endothelial
      cell against stress. However, the potential effects of BMVEC autophagy on BBB
      permeability during I/R and the mechanisms underlying these effects have yet to
      be elucidated. In the current study, we answered these questions by using
      chemical modulators of autophagy, including rapamycin and lithium carbonate
      acting, respectively, as mammalian target of rapamycin (mTOR)-dependent and mTOR
      independent autophagy inducers and 3-methyladenine (3-MA) as an autophagy
      inhibitor. To mimic I/R injury, BMVECs were exposed to oxygen-glucose
      deprivation/reoxygenation (OGD/R), and a rat transient middle cerebral artery
      occlusion/reperfusion (MCAO/R) model was performed. All the drugs were given at
      0.5 h before OGD/R or MCAO/R. First, enhancement of autophagy by rapamycin and
      lithium carbonate attenuated, whereas suppression of autophagy by 3-MA
      intensified BMVEC apoptosis and the high level of ROS induced by OGD/R. In
      addition, rapamycin and lithium carbonate pretreatments significantly reversed
      the decreased level of tight junction protein zonula occludens-1 (ZO-1) induced
      by OGD/R and promoted the distribution of ZO-1 on cell membranes. Finally,
      pretreatments with rapamycin and lithium carbonate reduced evans blue
      extravasation and brain water content in the ischemic hemisphere of the rat. In
      contrast, 3-MA pretreatment exerted opposite effects both in vitro and in vivo.
      These results may indicate a beneficial effect of BMVEC autophagy on BBB
      integrity during I/R injury. 

PMID- 25070049
TI  - MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and
      reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway.
AB  - Epithelial-mesenchymal transition (EMT) contributes to tumor invasion and
      metastasis in many cancers and correlates highly with the acquisition of cancer
      stem cell (CSC) characteristics. EMT also correlates with changes in specific
      microRNAs (miRNAs) that have already been integrated into tumorigenic programs as
      either oncogenes or tumor suppressor genes. Here, we show that miR-7, which was
      downregulated in breast CSCs (BCSCs) isolated from the human MCF-7 and MDA-MB-231
      cell lines, inhibited cell invasion and metastasis, decreased the BCSC population
      and partially reversed EMT in MDA-MB-231 cells by directly targeting the
      oncogene, SETDB1. The conspicuous epigenetic transition induced by miR-7
      overexpression was found not only in MDA-MB-231 cells but also in BCSC xenograft
      tumors. MiR-7 inhibited the metastasis of BCSCs in lungs, kidneys, and adrenal
      glands of NOD/SCID mice. ChIP-polymerase chain reaction result suggested that the
      SETDB1 induced STAT3 expression by binding to the promoter of STAT3. MiR-7
      mediated downregulation of SETDB1 resulted in the suppression of STAT3, which led
      to the downregulation of c-myc, twist, and mir-9. In addition, the downregulation
      of miR-7 in BCSCs may be indirectly attributed to lincRNA HOTAIR by modulating
      the expression of HoxD10 that promotes the expression of miR-7. These findings
      demonstrate that miR-7 was a tumor suppressor and that the overexpression of miR
      7 might serve as a good strategy for treating highly invasive breast cancer.

PMID- 25070050
TI  - Can celiac serology alone be used as a marker of duodenal mucosal recovery in
      children with celiac disease on a gluten-free diet?
AB  - OBJECTIVES: Assessment of treatment response in children with celiac disease (CD)
      after commencing a strict gluten-free diet (GFD) is generally based on the
      resolution of clinical features and normalization of serology. Recent adult
      studies have shown that serologic markers do not correlate with mucosal recovery.
      We aimed (i) to determine whether anti-tissue transglutaminase immunoglobulin
      (Ig)A (tTG) and anti-deamidated gliadin peptide IgG (DGP) antibodies are
      sensitive and specific markers of mucosal recovery in children with CD on a GFD
      for at least 12 months, and (ii) to determine whether a validated dietary
      questionnaire of compliance can identify patients with mucosal recovery. METHODS:
      A total of 150 children with biopsy-proven CD were prospectively evaluated with
      duodenal biopsies at >=12 months on GFD, paired with repeat tTG and DGP serology.
      The biopsies were reviewed in a blinded manner by two histopathologists and
      graded by Marsh criteria. A validated questionnaire of dietary compliance was
      also administered. RESULTS: Of 150 children recruited, 27 (18%) had positive
      serology, 97 (65%) had negative serology, and 26 (17%) had equivocal serology. Of
      the 97 children with negative serology, none had Marsh type 3 enteropathy. Of the
      27 patients with positive serology, only 6 had Marsh type 3 changes. The
      sensitivity and specificity of serology as a marker of significant mucosal
      pathology was 75 and 85%, respectively, with a positive predictive value of 22%
      but a negative predictive value of 98%. Of the 129 (86%) questionnaires
      completed, 88% reported good or excellent compliance with a GFD (negative
      predictive value 97%). CONCLUSIONS: This study suggests that follow-up using two
      serological tests in children with CD on a GFD may obviate the need for repeat
      mucosal biopsy in the majority of patients. A standardized dietary questionnaire
      may be useful in identifying patients who require further evaluation.

PMID- 25070051
TI  - Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome
      and chronic idiopathic constipation: systematic review and meta-analysis.
AB  - OBJECTIVES: Irritable bowel syndrome (IBS) and chronic idiopathic constipation
      (CIC) are functional bowel disorders. Evidence suggests that disturbance in the
      gastrointestinal microbiota may be implicated in both conditions. We performed a
      systematic review and meta-analysis to examine the efficacy of prebiotics,
      probiotics, and synbiotics in IBS and CIC. METHODS: MEDLINE, EMBASE, and the
      Cochrane Controlled Trials Register were searched (up to December 2013).
      Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which
      compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were
      eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of
      remaining symptomatic after therapy, with a 95% confidence interval (CI).
      Continuous data were pooled using a standardized or weighted mean difference with
      a 95% CI. RESULTS: The search strategy identified 3,216 citations. Forty-three
      RCTs were eligible for inclusion. The RR of IBS symptoms persisting with
      probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial
      effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for
      prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have
      beneficial effects in CIC (mean increase in number of stools per week=1.49; 95%
      CI=1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial
      (RR of failure to respond to therapy=0.78; 95% CI 0.67-0.92). Again, trials for
      prebiotics were few in number, and no definite conclusions could be drawn.
      CONCLUSIONS: Probiotics are effective treatments for IBS, although which
      individual species and strains are the most beneficial remains unclear. Further
      evidence is required before the role of prebiotics or synbiotics in IBS is known.
      The efficacy of all three therapies in CIC is also uncertain.

PMID- 25070052
TI  - miRNAs affect the expression of innate and adaptive immunity proteins in celiac
      disease.
AB  - OBJECTIVES: microRNAs (miRNAs) are short RNAs that regulate gene expression in
      various processes, including immune response. Altered immune response is a
      pivotal event in the pathogenesis of celiac disease (CD), and miRNAs could have a
      role in modulating both innate and adaptive response to gluten in celiac
      patients. METHODS: We compared miRNA profiles in duodenal biopsies of controls
      and CD patients by miRNA array. Differentially expressed miRNAs were validated in
      controls, Marsh 3A-B, and Marsh 3C patients by quantitative PCR (qPCR). Target
      gene expression was assessed by qPCR, western blotting, and immunohistochemistry,
      and the effect of gliadin was evaluated by in vitro stimulation experiments on
      duodenal biopsies. RESULTS: Seven miRNAs were identified as significantly
      downregulated in the duodenum of adult CD patients as compared with controls.
      qPCR validated the decreased expression of miR-192-5p, miR-31-5p, miR-338-3p, and
      miR-197, in particular in patients with more severe histological lesions (Marsh
      3C). In silico analysis of possible miRNA targets identified several genes
      involved in innate and adaptive immunity. Among these, chemokine C-X-C motif
      ligand 2 (CXCL2) and NOD2 showed significantly increased mRNA and protein level
      in Marsh 3C patients and a significant inverse correlation with the regulatory
      miR-192-5p. In addition, forkhead box P3 (FOXP3), Run-related transcription
      factor 1, and interleukin-18 (targets of miR-31-5p, miR-338-3p, and miR-197,
      respectively) showed upregulation in CD patients. Furthermore, alterations in
      CXCL2 and NOD2, FOXP3, miR-192-5p, and miR-31-5p expression were triggered by
      gliadin exposure in CD patients. CONCLUSIONS: miRNA expression is significantly
      altered in duodenal mucosa of CD patients, and this alteration can increase the
      expression of molecules involved in immune response.

PMID- 25070053
TI  - Impact of diabetes mellitus on clinical outcomes in patients undergoing surgical
      resection for pancreatic cancer: a retrospective, cohort study.
AB  - OBJECTIVES: Diabetes mellitus (DM) has a bidirectional association with
      pancreatic cancer (PaC); however, its effect on clinical outcomes has not been
      thoroughly evaluated. We analyzed these data in a large sample of PaC subjects
      who had undergone surgical resection. METHODS: Subjects enrolled in the Mayo
      Clinic Pancreatic Cancer SPORE registry from 2000 to 2010 who had resection with
      curative intent were identified (n=488). Tumor size, cancer stage, and
      postoperative median survival were evaluated. Median survivals were compared with
      Kaplan-Meier curves and Cox proportional hazards regression modeling. RESULTS: A
      total of 275 (56%) subjects had DM before surgery. DM subjects had larger tumors
      compared with those without DM (3.6 cm vs. 3.3, P=0.002), even after controlling
      for covariates including age, body mass index, and tumor grade. Cancer stage at
      the time of surgery was not affected by DM status (P=0.575). Preoperative DM was
      not associated with an increased risk of death using a multivariable survival
      analysis (hazard ratio 1.06, 95% confidence interval 0.81-1.38, P=0.676). The
      median survival following cancer resection was similar between subjects with and
      without DM (24 vs. 26 months, P=0.610). In addition, postoperative survival was
      similar on the basis of the duration of DM (new-onset vs. long-standing) and
      prior use of antidiabetic treatments in diabetic subjects. CONCLUSIONS: PaC
      subjects with DM have larger tumors than nondiabetic subjects. Despite this
      observation, preoperative DM does not negatively impact the cancer stage at the
      time of surgery or postoperative survival. Thus, the effect of DM on tumor size
      is either overshadowed by early metastatic spread of the cancer or is mitigated
      by the tumor resection.

PMID- 25070054
TI  - The effect of fiber supplementation on irritable bowel syndrome: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: Fiber has been used for many years to treat irritable bowel syndrome
      (IBS). This approach had fallen out of favor until a recent resurgence, which was
      based on new randomized controlled trial (RCT) data that suggested it might be
      effective. We have previously conducted a systematic review of fiber in IBS, but
      new RCT data for fiber therapy necessitate a new analysis; thus, we have
      conducted a systematic review of this intervention. METHODS: MEDLINE, EMBASE, and
      the Cochrane Controlled Trials Register were searched up to December 2013. Trials
      recruiting adults with IBS, which compared fiber supplements with placebo,
      control therapy, or "usual management", were eligible. Dichotomous symptom data
      were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy
      as well as number needed to treat (NNT) with a 95% confidence interval (CI).
      RESULTS: We identified 14 RCTs involving 906 patients that had evaluated fiber in
      IBS. There was a significant benefit of fiber in IBS (RR=0.86; 95% CI 0.80-0.94
      with an NNT=10; 95% CI=6-33). There was no significant heterogeneity between
      results (I(2)=0%, Cochran Q=13.85 (d.f.=14), P=0.46). The benefit was only seen
      in RCTs on soluble fiber (RR=0.83; 95% CI 0.73-0.94 with an NNT=7; 95% CI 4-25)
      with no effect seen with bran (RR=0.90; 95% CI 0.79-1.03). CONCLUSIONS: Soluble
      fiber is effective in treating IBS. Bran did not appear to be of benefit,
      although we did not uncover any evidence of harm from this intervention, as
      others have speculated from uncontrolled data.

PMID- 25070055
TI  - Influence of colonoscopy quality measures on patients' colonoscopist selection.
AB  - OBJECTIVES: The Affordable Care Act emphasizes the use of quality metrics and
      greater patient understanding of health-care options and access to physician
      performance data. The objectives of this study were to determine patients'
      familiarity with colonoscopy quality measures (CQMs) and their influence on
      patient selection of a colonoscopist. METHODS: A prospective survey of patients
      before screening or surveillance colonoscopy at university hospital, community
      hospital, and ambulatory procedure center endoscopy units was performed from 2011
      to 2012. RESULTS: Among the 417 participants, 20% (85/417) researched their
      physician's rating. The rates of familiarity with CQM were 88 % (353/402) for
      adequate bowel preparation, 30% (118/398) for adenoma detection rate (ADR), 26%
      (102/397) for cecal intubation rate, and 21% (82/394) for greater-than-6-min
      withdrawal time. Ninety-six percent (366/386) believed that colonoscopists'
      reporting of ADR to other physicians was important or very important. In
      selecting a colonoscopist, primary care provider referral was ranked as the first
      or second-most important of four factors in 87% (339/391). Even among patients
      who responded "it is very important" to report CQM to other doctors and patients,
      none ranked CQM as the most important factor in selecting a colonoscopist.
      CONCLUSIONS: Patient awareness of CQM, other than adequate bowel preparation, was
      low. Quality measure reporting is important to patients, but primary care
      provider referral was the most important factor in colonoscopist selection. This
      suggests that primary care providers, as well as patients, are important to
      include in educational strategies regarding quality metrics.

PMID- 25070056
TI  - Effect of increased bile acid synthesis or fecal excretion in irritable bowel
      syndrome-diarrhea.
AB  - OBJECTIVES: Approximately 25% of patients with irritable bowel syndrome-diarrhea
      (IBS-D) have increased total fecal bile acids (BA) and serum C4 (surrogate for BA
      synthesis). BA synthesis-related genes (KLB and FGFR4) are associated with
      colonic transit (CT) in IBS-D. Our aims were: (i) to compare phenotype and
      pathophysiology in IBS-D patients with increased or normal fecal excretion or
      synthesis of BA; and (ii) to explore association of variations in two candidate
      bile-acid synthesis genes (KLB and FGFR4) in these two subgroups of IBS-D.
      METHODS: A total of 64 IBS-D patients underwent on one occasion: fasting serum C4
      and FGF19, total fecal fat and BA excretion, CT, intestinal and colonic
      permeability, and candidate genotyping (rs17618244 (KLB), rs351855 (FGFR4)).
      Colonic sensation and tone were measured in 47 of the IBS-D patients. IBS-D
      subgroups were identified by fecal BA >2,337 mM per 48 h or by serum C4 >47.1
      ng/ml. RESULTS: IBS-D patients with fecal BA >2,337 mM per 48 h (19/54) had
      significantly greater body mass index, fecal fat, percent chenodeoxycholic acid
      (CDCA) in feces, and intestinal permeability, and borderline increased CT
      (P=0.13). Those IBS-D patients with serum C4 >47.1 ng/ml (13/54) had increased
      total fecal BA excretion and borderline increased colonic permeability. Variants
      in genes involved in feedback regulation of BA synthesis (KLB, P=0.06 and FGFR4,
      P=0.09) were potentially associated with the subgroup with elevated serum C4.
      CONCLUSIONS: IBS-D with increased BA excretion or synthesis is associated with
      significant pathophysiological changes relative to patients with normal BA
      profile. BA diarrhea is identified more effectively with total fecal BA than with
      serum C4.

PMID- 25070057
TI  - Guidelines on genetic evaluation and management of Lynch syndrome: a consensus
      statement by the US Multi-society Task Force on colorectal cancer.
AB  - The Multi-Society Task Force, in collaboration with invited experts, developed
      guidelines to assist health care providers with the appropriate provision of
      genetic testing and management of patients at risk for and affected with Lynch
      syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool
      to screen individuals in the office or endoscopy setting; Figure 2 illustrates a
      strategy for universal screening for Lynch syndrome by tumor testing of patients
      diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic
      evaluation of affected and at-risk family members of pedigrees with Lynch
      syndrome; Table 10 provides guidelines for screening at-risk and affected persons
      with Lynch syndrome; and Table 12 lists the guidelines for the management of
      patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the
      methodology utilized to derive these guidelines, as well as an explanation of,
      and supporting literature for, these guidelines are provided. 

PMID- 25070058
TI  - Racial differences in the progression to cirrhosis and hepatocellular carcinoma
      in HCV-infected veterans.
AB  - OBJECTIVES: The race of patients infected with hepatitis C virus (HCV) in the
      United States may be associated with the risk for cirrhosis and hepatocellular
      carcinoma (HCC). However, previous studies are too small to provide convincing
      data regarding the effect of race on cirrhosis and HCC risk after accounting for
      demographic, clinical, and virological factors. METHODS: We used the Veterans
      Administration (VA) HCV Clinical Case Registry to identify patients with
      confirmed viremia between 2000 and 2009 and with at least 1 year of follow-up in
      the VA. We identified cirrhosis and HCC cases through early 2010. Cox
      proportional hazard regression models were performed to examine the effect of
      race on the risk for cirrhosis and HCC while adjusting for patients' age, gender,
      period of service (World War I/II, Vietnam era, post-Vietnam era), HIV
      coinfection, HBV coinfection, alcohol abuse, diabetes, body mass index, and
      antiviral treatment receipt and response. RESULTS: There were 149,407 patients
      with active HCV viremia. Of them, 56.3% were non-Hispanic White (NHW), 36.1% were
      African American (AA), 6.0% were Hispanic, and 1.6% belonged to other racial
      groups. After an average follow-up of 5.2 years, 13,099 patients were seen to
      have a recorded diagnosis of cirrhosis and 3,551 had HCC. Hispanics had the
      highest annual incidence rates of cirrhosis and HCC (28.8 and 7.8%,
      respectively), whereas AAs had the lowest rates (13.3% and 3.9%, respectively)
      compared with NHWs (21.6 and 4.7%, respectively). There were differences among
      NHW, AA, and Hispanic patients in the rates of HIV infection (2.1, 2.5, and 6.0%,
      respectively), HCV genotype 1 (50.0, 50.6, and 64.2%, respectively), obesity
      (28.0, 25.4, and 30.9%, respectively), diabetes (8.7, 16.1, and 16.1%,
      respectively), and absence of antiviral treatment (81.1, 89.6, and 82.1%,
      respectively). However, adjusting for differences in demographic and clinical
      factors did not change the magnitude or direction of the race effect. Compared
      with NHWs, Hispanic patients had a higher risk of having cirrhosis recorded
      (adjusted hazard ratio (HR)=1.28, 95% confidence interval (CI)=1.21-1.37) and HCC
      (1.61, 95% CI=1.44-1.80). In contrast, AAs had a lower risk of cirrhosis
      (HR=0.58, 95% CI=0.55-0.60) and HCC (0.77, 95% CI=0.71-0.83) compared with NHWs.
      CONCLUSIONS: Hispanics with HCV are at a significantly higher risk, whereas AAs
      are at a considerably lower risk of developing cirrhosis and HCC than are NHWs.
      These associations persisted even after adjusting for a range of factors
      including HCV genotype, HCV treatment, diabetes, and body mass index.

PMID- 25070059
TI  - Cancer-associated fibroblasts from invasive breast cancer have an attenuated
      capacity to secrete collagens.
AB  - Normal fibroblasts produce extracellular matrix (ECM) components that form the
      structural framework of tissues. Cancer-associated fibroblasts (CAFs) with an
      activated phenotype mainly contribute to ECM deposition and construction of
      cancer masses. However, the stroma of breast cancer tissues has been shown to be
      more complicated, and the mechanisms through which CAFs influence ECM deposition
      remain elusive. In this study, we found that the activated fibroblast marker
      alpha-smooth muscle actin (alpha-SMA) was only present in the stroma of breast
      cancer tissue, and the CAFs isolated from invasive breast cancer sample remained
      to be activated and proliferative in passages. To further assess the difference
      between CAFs and normal breast fibroblasts (NFs), MALDI TOF/TOF-MS was used to
      analyze the secretory proteins of primary CAFs and NFs. In total, 2,903 and 3,023
      proteins were identified. Mass spectrum quantitative assay and data analysis for
      extracellular proteins indicated that the CAFs produce less collagens and matrix
      degrading enzymes compared with NFs. This finding was confirmed by western blot
      analysis. Furthermore, we discovered that reduced collagen deposition was present
      in the stroma of invasive breast cancer. These studies showed that although CAFs
      from invasive breast cancer possess an activated phenotype, they secreted less
      collagen and induced less ECM deposition in cancer stroma. In cancer tissue, the
      remodeling of stromal structure and tumor microenvironment might, therefore, be
      attributed to the biological changes in CAFs including their protein expression
      profile. 

PMID- 25070061
TI  - Importance of serum adipokine and ghrelin levels in patients with Crimean-Congo
      hemorrhagic fever.
AB  - Crimean-Congo Hemorrhagic Fever (CCHF) may present with a mild clinical course or
      else exhibit a severe profile with potentially fatal hemorrhaging. The
      pathogenesis of the disease has not yet been well described. Cytokines have
      recently been investigated in order to explain the pathogenesis. The latest
      reports show that adipokines are powerful inflammation modulators. This study
      investigated the effect of adipokines (resistin, leptin, and adiponectin) and
      ghrelin on disease severity in CCHF patients by testing their serum levels. This
      retrospective study was conducted with patients with CCHF hospitalized at the
      Karadeniz Technical University, Medical Faculty in Turkey. Patients were divided
      into severe and non-severe groups. Serum adipokine levels of patients with CCHF
      were measured using enzyme-linked immunosorbent assay (ELISA). Fifty-three
      patients with confirmed CCHF were investigated. Twenty-five (47.2%) of these
      patients constituted the severe group. Serum resistin levels in the severe and
      non-severe groups were 108.9 +/- 24.7 ng/ml and 77.5 +/- 27.7 ng/ml (P < 0.001),
      leptin levels 15.5 +/- 9.8 and 11.2 +/- 5.1 ng/ml (P = 0.074), adiponectin levels
      26.8 +/- 18.9 and 27.4 +/- 16.3 ng/ml (P = 0.903) and ghrelin levels 57.1 +/-
      48.7 and 200.9 +/- 182.7 ng/ml (P = 0.001), all respectively. This study confirms
      that significant changes in serum levels of resistin and ghrelin take place in
      severe CCHF.

PMID- 25070060
TI  - Audio-visuomotor processing in the musician's brain: an ERP study on professional
      violinists and clarinetists.
AB  - The temporal dynamics of brain activation during visual and auditory perception
      of congruent vs. incongruent musical video clips was investigated in 12 musicians
      from the Milan Conservatory of music and 12 controls. 368 videos of a clarinetist
      and a violinist playing the same score with their instruments were presented. The
      sounds were similar in pitch, intensity, rhythm and duration. To produce an
      audiovisual discrepancy, in half of the trials, the visual information was
      incongruent with the soundtrack in pitch. ERPs were recorded from 128 sites. Only
      in musicians for their own instruments was a N400-like negative deflection
      elicited due to the incongruent audiovisual information. SwLORETA applied to the
      N400 response identified the areas mediating multimodal motor processing: the
      prefrontal cortex, the right superior and middle temporal gyrus, the premotor
      cortex, the inferior frontal and inferior parietal areas, the EBA, somatosensory
      cortex, cerebellum and SMA. The data indicate the existence of audiomotor mirror
      neurons responding to incongruent visual and auditory information, thus
      suggesting that they may encode multimodal representations of musical gestures
      and sounds. These systems may underlie the ability to learn how to play a musical
      instrument. 

PMID- 25070063
TI  - Diversity and spatiotemporal dynamics of bacterial communities: physicochemical
      and other drivers along an acid mine drainage.
AB  - Deciphering the biotic and abiotic factors that control microbial community
      structure over time and along an environmental gradient is a pivotal question in
      microbial ecology. Carnoules mine (France), which is characterized by acid waters
      and very high concentrations of arsenic, iron, and sulfate, provides an excellent
      opportunity to study these factors along the pollution gradient of Reigous Creek.
      To this end, biodiversity and spatiotemporal distribution of bacterial
      communities were characterized using T-RFLP fingerprinting and high-throughput
      sequencing. Patterns of spatial and temporal variations in bacterial community
      composition linked to changes in the physicochemical conditions suggested that
      species-sorting processes were at work in the acid mine drainage. Arsenic,
      temperature, and sulfate appeared to be the most important factors that drove the
      composition of bacterial communities along this continuum. Time series
      investigation along the pollution gradient also highlighted habitat
      specialization for some major members of the community (Acidithiobacillus and
      Thiomonas), dispersal for Acidithiobacillus, and evidence of extinction/re
      thriving processes for Gallionella. Finally, pyrosequencing revealed a broader
      phylogenetic range of taxa than previous clone library-based diversity. Overall,
      our findings suggest that in addition to environmental filtering processes,
      additional forces (dispersal, birth/death events) could operate in AMD community.

PMID- 25070062
TI  - Assessing the tobacco-rattle-virus-based vectors system as an efficient gene
      silencing technique in Datura stramonium (Solanaceae).
AB  - Datura stramonium is a well-known medicinal plant, which is important for its
      alkaloids. There are intrinsic limitations for the natural production of
      alkaloids in plants; metabolic engineering methods can be effectively used to
      conquer these limitations. In order for this the genes involved in corresponding
      pathways need to be studied. Virus-Induced Gene Silencing is known as a
      functional genomics technique to knock-down expression of endogenous genes. In
      this study, we silenced phytoene desaturase as a marker gene in D. stramonium in
      a heterologous and homologous manner by tobacco-rattle-virus-based VIGS vectors.
      Recombinant TRV vector containing pds gene from D. stramonium (pTRV2-Dspds) was
      constructed and injected into seedlings. The plants injected with pTRV2-Dspds
      showed photobleaching 2 weeks after infiltration. Spectrophotometric analysis
      demonstrated that the amount of chlorophylls and carotenoids in leaves of the
      bleached plants decreased considerably compared to that of the control plants.
      Semi-Quantitative RT-PCR results also confirmed that the expression of pds gene
      in the silenced plants was significantly reduced in comparison with the control
      plants. The results showed that the viral vector was able to influence the levels
      of total alkaloid content in D. stramonium. Our results illustrated that TRV
      based VIGS vectors are able to induce effective and reliable functional gene
      silencing in D. stramonium as an alternative tool for studying the genes of
      interest in this plant, such as the targeted genes in tropane alkaloid
      biosynthetic pathway. The present work is the first report of establishing VIGS
      as an efficient method for transient silencing of any gene of interest in D.
      stramonium.

PMID- 25070064
TI  - Hyphomonas beringensis sp. nov. and Hyphomonas chukchiensis sp. nov., isolated
      from surface seawater of the Bering Sea and Chukchi Sea.
AB  - Two Gram-negative, non-spore-forming, oval to pear shaped motile strains,
      designated 25B14_1(T) and BH-BN04-4(T), isolated from surface seawater from the
      Bering Sea and Chukchi Sea, respectively, were subjected to polyphasic taxonomic
      study. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that
      strains 25B14_1(T) and BH-BN04-4(T) clustered together with Hyphomonas atlanticus
      22II1-22F38(T) and Hyphomonas oceanitis DSM 5155(T), respectively, within genus
      Hyphomonas. Based on whole genome sequence analysis, the calculated DDH and ANIm
      values between strain 25B14_1(T) and BH-BN04-4(T) are 18.8 and 83.19%
      respectively. The calculated DDH values of strain 25B14_1(T) and BH-BN04-4(T)
      with seven type strains ranged from 18.2 to 19.9% and from 18.4 to 40.4%,
      respectively. The ANIm values of strain 25B14_1(T) and BH-BN04-4(T) with seven
      type strains ranged from 83.00 to 84.67% and from 83.14 to 90.58%, respectively.
      Both isolates were found to contain Q-11 as the predominant respiratory quinone.
      The major fatty acids of strain 25B14_1(T) were identified as C(16:0), C(17:0),
      C(18:1)omega7c-methyl and Summed Feature 8 (C(18:1)omega6c/omega7c as defined by
      MIDI), while in the case of strain BH-BN04-4(T) they were identified as C(16:0),
      C(18:1)omega7c-methyl and Summed Feature 8 (C(18:1)omega6c/omega7c). The G+C
      contents of 25B14_1(T) and BH-BN04-4(T) were determined to be 58.4 and 61.0 mol%,
      respectively. The combined phenotypic and genotypic data show that the two
      isolates each represent novel species of the genus Hyphomonas, for which the
      names Hyphomonas beringensis sp. nov. and Hyphomonas chukchiensis sp. nov. are
      proposed, with the type strain 25B14_1(T) (=MCCC 1A07321(T) = LMG 27914(T)) and
      BH-BN04-4(T) (=MCCC 1A07481(T) = LMG 27915(T)), respectively.

PMID- 25070065
TI  - The sensitivity of gamma-index method to the positioning errors of high
      definition MLC in patient-specific VMAT QA for SBRT.
AB  - BACKGROUND: To investigate the sensitivity of various gamma criteria used in the
      gamma-index method for patient-specific volumetric modulated arc therapy (VMAT)
      quality assurance (QA) for stereotactic body radiation therapy (SBRT) using a
      flattening filter free (FFF) photon beam. METHODS: Three types of intentional
      misalignments were introduced to original high-definition multi-leaf collimator
      (HD-MLC) plans. The first type, referred to Class Out, involved the opening of
      each bank of leaves. The second type, Class In, involved the closing of each bank
      of leaves. The third type, Class Shift, involved the shifting of each bank of
      leaves towards the ground. Patient-specific QAs for the original and the modified
      plans were performed with MapCHECK2 and EBT2 films. The sensitivity of the gamma
      index method using criteria of 1%/1 mm, 1.5%/1.5 mm, 1%/2 mm, 2%/1 mm and 2%/2 mm
      was investigated with absolute passing rates according to the magnitudes of MLCs
      misalignments. In addition, the changes in dose-volumetric indicators due to the
      magnitudes of MLC misalignments were investigated. The correlations between
      passing rates and the changes in dose-volumetric indicators were also
      investigated using Spearman's rank correlation coefficient (gamma). RESULTS: The
      criterion of 2%/1 mm was able to detect Class Out and Class In MLC misalignments
      of 0.5 mm and Class Shift misalignments of 1 mm. The widely adopted clinical
      criterion of 2%/2 mm was not able to detect 0.5 mm MLC errors of the Class Out or
      Class In types, and also unable to detect 3 mm Class Shift errors. No
      correlations were observed between dose-volumetric changes and gamma passing
      rates (gamma < 0.8). CONCLUSIONS: Gamma criterion of 2%/1 mm was found to be
      suitable as a tolerance level with passing rates of 90% and 80% for patient
      specific VMAT QA for SBRT when using MapCHECK2 and EBT2 film, respectively.

PMID- 25070066
TI  - Fast response and highly selective sensing of amine vapors using a luminescent
      coordination polymer.
AB  - Detecting volatile amines is a significant topic in the quality control of food
      and medical diagnosis. We report the first Eu-coordination polymer (CP) as a
      sensory material for the detection of a class of amine vapors with high
      selectivity and rapid response. 

PMID- 25070067
TI  - An electronic screen for triaging adolescent substance use by risk levels.
AB  - IMPORTANCE: Screening adolescents for substance use and intervening immediately
      can reduce the burden of addiction and substance-related morbidity. Several
      screening tools have been developed to identify problem substance use for
      adolescents, but none have been calibrated to triage adolescents into clinically
      relevant risk categories to guide interventions. OBJECTIVE: To describe the
      psychometric properties of an electronic screen and brief assessment tool that
      triages adolescents into 4 actionable categories regarding their experience with
      nontobacco substance use. DESIGN, SETTING, AND PARTICIPANTS: Adolescent patients
      (age range, 12-17 years) arriving for routine medical care at 2 outpatient
      primary care centers and 1 outpatient center for substance use treatment at a
      pediatric hospital completed an electronic screening tool from June 1, 2012,
      through March 31, 2013, that consisted of a question on the frequency of using 8
      types of drugs in the past year (Screening to Brief Intervention). Additional
      questions assessed severity of any past-year substance use. Patients completed a
      structured diagnostic interview (Composite International Diagnostic Interview
      Substance Abuse Module), yielding Diagnostic and Statistical Manual of Mental
      Disorders (Fifth Edition) substance use diagnoses. MAIN OUTCOMES AND MEASURES:
      For the entire screen and the Screening to Brief Intervention, sensitivity and
      specificity for identifying nontobacco substance use, substance use disorders,
      severe substance use disorders, and tobacco dependence were calculated using the
      Composite International Diagnostic Interview-Substance Abuse Module as the
      criterion standard. RESULTS: Of 340 patients invited to participate, 216 (63.5%)
      enrolled in the study. Sensitivity and specificity were 100% and 84% (95% CI, 76%
      89%) for identifying nontobacco substance use, 90% (95% CI, 77%-96%) and 94% (95%
      CI, 89%-96%) for substance use disorders, 100% and 94% (95% CI, 90%-96%) for
      severe substance use disorders, and 75% (95% CI, 52%-89%) and 98% (95% CI, 95%
      100%) for nicotine dependence. No significant differences were found in
      sensitivity or specificity between the full tool and the Screening to Brief
      Intervention. CONCLUSIONS AND RELEVANCE: A single screening question assessing
      past-year frequency use for 8 commonly misused categories of substances appears
      to be a valid method for discriminating among clinically relevant risk categories
      of adolescent substance use.

PMID- 25070068
TI  - Differential production of phytotoxins from Phomopsis sp. from grapevine plants
      showing esca symptoms.
AB  - Nine strains of the fungus Phomopsis spp. were isolated from a vineyard showing
      decline from the disease esca. Strains were screened for their ability to produce
      secondary metabolites showing chemical diversity. The culture extracts of each
      strain were analyzed by liquid chromatography-ultraviolet-diode array detection
      mass spectrometry. Three strains were selected for the isolation and
      characterization of eight of the major metabolites. Structures were elucidated by
      spectroscopic analyses including two-dimensional NMR and mass spectrometry and by
      comparison to literature data. Among the isolated metabolites were the known
      phomopsolide B (1), sydowinin A (6), sydowinol (7), cytosporone B (8), and four
      new furanones named phomopsolidones A-D (2-5). The fungal strains were identified
      as Phomopsis sp., Phomopsis viticola Sacc and, Phomopsis viticola complex.
      Biological assays on Vitis vinifera leaves and callus tissue, antibacterial, and
      insecticidal activities were evaluated. The results revealed variability
      regarding secondary metabolites with species of Phomopsis sp. associated with
      grapevine, raising the question of cultivar-driven strain selection and
      phytotoxins biosynthesis in grapevine plants. 

PMID- 25070069
TI  - Pharmacokinetics of gentamicin in newborns with moderate-to-severe hypoxic
      ischemic encephalopathy undergoing therapeutic hypothermia.
AB  - OBJECTIVE: To investigate gentamicin pharmacokinetics in neonates with moderate
      to-severe hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic
      hypothermia (TH). METHODS: Data were collected retrospectively from infants
      admitted between January 2007 and February 2011. Gentamicin was given at 2.5
      mg/kg/dose q12h intravenously. Infants not eligible for TH underwent therapeutic
      normothermia (TN). After reviewing the data which showed >85 % of infants
      undergoing TH had gentamicin trough concentration >2 ug/ml at steady state, the
      gentamicin level monitoring protocol was modified since March 2011. RESULTS: In
      the initial retrospective study, 15 TN infants were compared with 19 TH infants.
      There was significant difference in median gentamicin half-life (7.01 vs. 9.57
      h). A higher proportion of infants in the TH group required dosage adjustment
      (8/15 vs. 17/19). After March 2011, gentamicin level taken 12-h post 1st dose was
      measured routinely and 18/22 infants had trough gentamicin levels >2 ug/ml. Their
      dosing intervals were extended to Q18h or beyond. CONCLUSIONS: Infants with
      moderate-to-severe HIE who undergo TH may exhibit changes in the pharmacokinetic
      properties of gentamicin compared to infants who undergo TN. By measuring
      gentamicin level at 12-h after the first dose of 2.5 mg/kg/dose, appropriate
      dosing interval can be determined and the duration of exposure to toxic
      gentamicin level can be reduced.

PMID- 25070070
TI  - Apoptosis inhibitor-5 overexpression is associated with tumor progression and
      poor prognosis in patients with cervical cancer.
AB  - BACKGROUND: The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is
      considered a key molecule in the tumor progression and malignant phenotype of
      tumor cells. Here, we investigated API5 expression in cervical cancer, its
      clinical significance, and its relationship with phosphorylated extracellular
      signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of
      cervical cancer. METHODS: API5 effects on cell growth were assessed in cervical
      cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed
      on a cervical cancer tissue microarray consisting of 173 primary cervical
      cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal
      tissues. RESULTS: API5 overexpression promoted cell proliferation and colony
      formation in CaSki cells, whereas API5 knockdown inhibited the both properties in
      HeLa cells. Immunohistochemical staining showed that API5 expression increased
      during the normal to tumor transition of cervical carcinoma (P < 0.001), and this
      increased expression was significantly associated with tumor stage (P = 0.004),
      tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5
      expression levels were positively associated with pERK1/2 in cervical cancer (P <
      0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P =
      0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic
      factors for overall survival. CONCLUSIONS: API5 expression is associated with
      pERK1/2 in a subset of cervical cancer patients and its expression predicts poor
      overall survival, supporting that API5 may be a promising novel target for
      therapeutic interventions.

PMID- 25070071
TI  - The value of biomarker comparisons between autosomal dominant and late-onset
      Alzheimer disease.

PMID- 25070072
TI  - Reduced affordability of cigarettes and socio-economic inequalities in smoking
      continuation in Stakhanov, Ukraine, 2009.
AB  - The recent tobacco excise tax increase and economic crisis reduced cigarette
      affordability in Ukraine dramatically. Using survey data from Stakhanov (n =
      1691), eastern Ukraine, we employed logistic regression analysis to examine
      whether socio-economic status was associated with the continuation of smoking in
      this environment in 2009. Low education (in women) and ownership of household
      assets (in men) were negatively associated with smoking continuation, whereas a
      positive association was found for personal monthly income. Our findings suggest
      that in a low-income setting where efficient cessation services are absent,
      reduced cigarette affordability may have only a limited effect in cutting down
      smoking.

PMID- 25070073
TI  - NHS leaders note: organisational culture is key.

PMID- 25070074
TI  - Effects of protein and carbohydrate on an insect herbivore: the vista from a
      fitness landscape.
AB  - Protein and carbohydrates are important nutrients driving the growth of
      herbivores; however, their content in plants is highly variable. Multiple studies
      have explored their effect on herbivores, but only one other study (using a
      caterpillar) has provided a comprehensive overview that includes a simultaneous
      evaluation of their ratios and concentrations. In the present work, we ran two
      experiments using nymphs of the generalist grasshopper Melanoplus differentialis.
      Grasshoppers and caterpillars differ in a number of important ways, which might
      affect their feeding and physiological responses to foods with variable content
      of protein and carbohydrates. First, in a choice experiment, we measured
      performance and related this to the self-selected intake of nutrients. No
      differences were found for duration of development across treatments, but gain in
      mass was lower on a diet of low macronutrient concentration. Consumption of
      protein was always tightly regulated, but intake of carbohydrate was
      significantly reduced when consuming diluted food. In the second experiment,
      insects were constrained to one of nine diets and we plotted performance and
      consumption using a fitness-landscape approach that mimics the natural variation
      of nutrients in plants. We found significant effects of protein and carbohydrate
      content on gain in mass and in duration of development. The concentration of
      macronutrients in the food had more pronounced effects than did the protein-to
      carbohydrate ratio. The protein-carbohydrate content also significantly affected
      the intake of food and energy (calories), production of frass, and digestive
      efficiency. On foods with low macronutrient concentration consumption was high,
      but digestive efficiency was low. Our results suggest that insects will favor
      protein-biased foods when the total macronutrient content of available foods is
      low, and that in the short-term compensatory feeding responses can overcome
      nutritional deficits and/or imbalances. However, over the long term, insect
      herbivores might pay substantial costs when eating foods that are nutritionally
      suboptimal. 

PMID- 25070075
TI  - One-pot synthesis of PEG modified BaLuF5:Gd/Yb/Er nanoprobes for dual-modal in
      vivo upconversion luminescence and X-ray bioimaging.
AB  - Polyethylene glycol (PEG) modified BaLuF5:Gd/Yb/Er upconversion nanoparticles
      (UCNPs) were synthesized by a facile one-pot hydrothermal method for simultaneous
      synthesis and surface functionalization. The novel, excellently biocompatible and
      water-soluble bioprobes were used for simultaneous upconversion (UC) luminescence
      and X-ray bioimaging for the first time. The as-prepared BaLuF5:Gd/Yb/Er UCNPs
      possess a face-centered cubic structure with an average size of 23.7 +/- 2.7 nm.
      Under 980 nm laser excitation, these UCNPs emitted intense UC luminescence via a
      two-photon process. In vitro bioimaging and localized luminescence spectra
      detected from HeLa cells and the background reveal that these UCNPs are ideal
      candidates for optical bioimaging in the absence of autofluorescence.
      Furthermore, the synergistic in vivo UC luminescence and X-ray bioimaging reveal
      that these PEG-modified BaLuF5:Gd/Yb/Er UCNPs can be successfully used as ideal
      dual-modal bioprobes. These results demonstrate that these PEG modified UCNPs are
      ideal multi-modal nanoprobes for bioimaging. 

PMID- 25070076
TI  - Prophylactic use of heparin for deep vein thrombosis in restrained psychiatric
      patients: a chart review.
AB  - OBJECTIVE: Physical restraint sometimes causes deep vein thrombosis (DVT) and
      pulmonary embolism. Although unfractionated heparin (UFH) is used for the
      prophylaxis of DVT, its effectiveness remained unknown for restrained patients.
      METHOD: We conducted a chart review of restrained inpatients at Sakuragaoka
      Memorial Hospital in Japan. Restrained patients received subcutaneous injection
      of UFH 5000 IU bid from December 2008 to September 2010 [heparin (+) period]
      while UFH was not used from December 2010 to September 2012 [heparin (-) period].
      A Doppler ultrasound scanning was performed to examine the presence of DVT. The
      incidence of DVT was compared between the two periods by chi-square test. A
      multiple logistic regression model was used to examine effects of demographic and
      clinical characteristics on the incidence of DVT. RESULTS: No significant
      difference was found in the incidence of DVT between the heparin (+) and (-)
      periods [11.8% (11/93) vs. 11.1% (13/117)]. Sedation [odds ratio (OR) = 3.78],
      physical comorbidities (OR = 6.29) and a longer duration of restraint (OR = 1.22)
      were associated with the incidence of DVT. CONCLUSION: The use of UFH was not
      associated with any reduction in the incidence of DVT in restrained psychiatric
      patients.

PMID- 25070077
TI  - Pyoderma gangrenosum, acne, psoriasis, arthritis and suppurative hidradenitis
      (PAPASH)-syndrome: a new entity within the spectrum of autoinflammatory
      syndromes?

PMID- 25070078
TI  - Potential Conflicting Interests for Surgeons in End-of-Life Care.
AB  - Thirty-day mortality represents a variable that is commonly used to measure the
      quality of surgical care. The definition of 30-day mortality and the application
      of a risk adjustment to its measurement may vary among different organizations
      comparing physician quality. In the midst of this confusion, conflicting
      interests arise for surgeons who must weigh the potential benefit of surgical
      interventions to individual patients versus the potential loss of access by
      future patients should 30-day mortality ratings be adversely affected. Similarly,
      surgeons may become adversely impacted by the lack of compensation from avoiding
      "high-risk" cases, but might face a more severe financial impact if they have a
      higher mortality rating compared to their peers. 

PMID- 25070079
TI  - Effect of a denture base acrylic resin containing silver nanoparticles on Candida
      albicans adhesion and biofilm formation.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of denture base
      resin containing silver nanoparticles (nano-silver) on Candida albicans adhesion
      and biofilm formation. BACKGROUND: Epidemiological studies report that
      approximately 70% of removable denture wearers suffer from denture stomatitis.
      Candida albicans adhesion and biofilm formation are regarded as essential
      prerequisites for denture stomatitis. MATERIALS AND METHODS: The bioactivity and
      biomass of C. albicans biofilm, which was incubated in a series of twofold
      dilutions of nano-silver suspension at 37 degrees C for 24 h, were determined
      using XTT reduction and crystal violet assays, respectively. The denture base
      resin specimens containing nano-silver were then used in C. albicans adhesion (37
      degrees C; 90 min; n = 9) and biofilm formation assays (37 degrees C; 72 h; n =
      9). Confocal laser scanning microscopy was used to evaluate the architectural
      properties of average thickness and live/dead cell ratio in the different biofilm
      stages that developed on the specimens. RESULTS: The bioactivity and biomass of
      C. albicans biofilm successively decreased with increasing nano-silver solution
      concentration. Denture base resin containing nano-silver had no effect on
      adhesion at low concentrations, but it exhibited anti-adhesion activity at a high
      concentration (5%). For 72 h biofilm formed on the resin specimens, the thickness
      and live/dead cell ratio were successively reduced with increasing nano-silver
      concentrations. CONCLUSION: Nano-silver had antifungal activity and inhibited C.
      albicans biofilm formation. Antifungal activity and an inhibitory effect on
      adhesion and biofilm formation by denture base resin containing nano-silver were
      discovered, especially at a higher concentration.

PMID- 25070080
TI  - siRNA-induced ABCE1 silencing inhibits proliferation and invasion of breast
      cancer cells.
AB  - Breast cancer is the most common type of cancer among females and the adenosine
      triphosphate (ATP) binding cassette E1 (ABCE1) gene is a member of the ATP
      binding cassette (ABC) family. Studies in lung cancer have shown that
      overexpression of ABCE1 in tumor cells promotes growth and inhibits apoptosis.
      However, little is known about whether the ABCE1 gene is associated with breast
      cancer. In the present study, ABCE1 expression was assessed in breast cancer
      tissue and adjacent normal breast tissue using immunohistochemistry. Furthermore,
      small interfering (si)RNA targeting ABCE1 was constructed and transfected into
      MCF-7 human breast cancer cells to downregulate ABCE1 expression. The effect of
      ABCE1 knockdown on cell proliferation, invasion, apoptosis and gene expression
      was then assessed using MTT assay, Transwell migration assay, flow cytometry and
      western blot analysis, respectively. ABCE1 was observed to be overexpressed in
      breast cancer tissue compared with adjacent normal breast tissue. Furthermore,
      ABCE1-siRNA was found to inhibit proliferation and invasion in breast cancer
      cells, significantly induce breast cancer cell apoptosis (P<0.05) in vitro and
      increase the protein expression of RNase L. These findings showed that ABCE1 had
      an important role in proliferation, invasion and apoptosis in MCF-7 human breast
      cancer cells and that ABCE1 may inhibit intracellular RNase L activity, which
      inhibits the 2-5A/RNase L pathway, interfering with the biological
      characteristics of breast cancer cells.

PMID- 25070082
TI  - Influence of nanosecond pulsed plasma on the non-enzymatic pathway for the
      generation of nitric oxide from L-arginine and the modification of graphite oxide
      to increase the solar cell efficiency.
AB  - In this work, we demonstrated the action of nanosecond pulsed plasma (NPP) on the
      generation of nitric oxide (NO) from the non-enzymatic pathway and on the
      modification of graphite oxide (GO) sheets to increase polymer solar cells (PSCs)
      efficiency. NO is an important signal and an effector molecule in animals, which
      is generated from the enzyme-catalyzed oxidation of L-arginine to NO and L
      citrulline. Hence, L-arginine is an important biological precursor for NO
      formation. Therefore, we developed a new non-enzymatic pathway for the formation
      of NO and L-citrulline using NPP and characterized the pathway using NO detection
      kit, NMR, liquid chromatography/capillary electrophoresis-mass spectrometry
      (LC/CE-MS) for both quantitative and qualitative bioanalysis. We then synthesized
      and modified the functional groups of GO using NPP, and it was characterised by X
      ray photoelectron spectroscopy (XPS), confocal Raman spectroscopy, scanning
      electron microscopy (SEM), transmission electron microscopy (TEM) imaging,
      cathodoluminescence (CL) and work function using gamma-FIB. Further, we also
      tested the power conversion efficiency of the PSCs devices with modified GO that
      is similar to the one obtained with poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) as HTL. This work is perceived to
      have great implications for inexpensive and efficient methodology for NO
      generation and modification of GO, which are applicable in materials from
      nanomaterials to biomolecules.

PMID- 25070081
TI  - A plant-specific HUA2-LIKE (HULK) gene family in Arabidopsis thaliana is
      essential for development.
AB  - In Arabidopsis thaliana, the HUA2 gene is required for proper expression of
      FLOWERING LOCUS C (FLC) and AGAMOUS, key regulators of flowering time and
      reproductive development, respectively. Although HUA2 is broadly expressed,
      plants lacking HUA2 function have only moderately reduced plant stature, leaf
      initiation rate and flowering time. To better understand HUA2 activity, and to
      test whether redundancy with similar genes underlies the absence of strong
      phenotypes in HUA2 mutant plants, we identified and subsequently characterized
      three additional HUA2-LIKE (HULK) genes in Arabidopsis. These genes form two
      clades (HUA2/HULK1 and HULK2/HULK3), with members broadly conserved in both
      vascular and non-vascular plants, but not present outside the plant kingdom.
      Plants with progressively reduced HULK activity had increasingly severe
      developmental defects, and plants homozygous for loss-of-function mutations in
      all four HULK genes were not recovered. Multiple mutants displayed reproductive,
      embryonic and post-embryonic abnormalities, and provide detailed insights into
      the overlapping and unique functions of individual HULK genes. With regard to
      flowering time, opposing influences were apparent: hua2 hulk1 plants were early
      flowering, while hulk2 hulk3 mutants were late-flowering, and hua2 acted
      epistatically to cause early flowering in all combinations. Genome-wide
      expression profiling of mutant combinations using RNA-Seq revealed complex
      transcriptional changes in seedlings, with FLC, a known target of HUA2, among the
      most affected. Our studies, which include characterization of HULK expression
      patterns and subcellular localization, suggest that the HULK genes encode
      conserved nuclear factors with partially redundant but essential functions
      associated with diverse genetic pathways in plants. 

PMID- 25070083
TI  - The hydrophobic effect revisited--studies with supramolecular complexes imply
      high-energy water as a noncovalent driving force.
AB  - Traditional descriptions of the hydrophobic effect on the basis of entropic
      arguments or the calculation of solvent-occupied surfaces must be questioned in
      view of new results obtained with supramolecular complexes. In these studies, it
      was possible to separate hydrophobic from dispersive interactions, which are
      strongest in aqueous systems. Even very hydrophobic alkanes associate
      significantly only in cavities containing water molecules with an insufficient
      number of possible hydrogen bonds. The replacement of high-energy water in
      cavities by guest molecules is the essential enthalpic driving force for
      complexation, as borne out by data for complexes of cyclodextrins, cyclophanes,
      and cucurbiturils, for which complexation enthalpies of up to -100 kJ mol(-1)
      were reached for encapsulated alkyl residues. Water-box simulations were used to
      characterize the different contributions from high-energy water and enabled the
      calculation of the association free enthalpies for selected cucurbituril
      complexes to within a 10% deviation from experimental values. Cavities in
      artificial receptors are more apt to show the enthalpic effect of high-energy
      water than those in proteins or nucleic acids, because they bear fewer or no
      functional groups in the inner cavity to stabilize interior water molecules.

PMID- 25070084
TI  - Committed Tc17 cells are phenotypically and functionally resistant to the effects
      of IL-27.
AB  - IL-17-secreting CD8(+) T cells (Tc17 cells) have been implicated in immunity to
      infections, cancer, and autoimmune diseases. Thus far, studies on Tc17 cells have
      primarily investigated their development from naive precursors, while the biology
      of committed Tc17 cells has been less characterized, in particular during the
      effector phase of immune responses. IL-27 is an important regulator of
      inflammation through the induction of regulatory Tr1 cells, as well as a
      suppressor of Th17-cell development. IL-27 suppresses the development of Tc17
      cells, but its effects on committed Tc17 cells are unknown. Here we demonstrate
      that even though IL-27 completely inhibited the development of C57BL/6 mouse Tc17
      cells, it had little effect on previously committed Tc17 cells. Although
      committed Tc17 cells were capable of responding to IL-27, it had no effect on
      expression of RORgammat and RORalpha, or production of various cytokines.
      Committed Tc17 cells did not express granzyme B and lacked cytotoxicity in vitro,
      features that remained unaltered by IL-27 treatment. Nonetheless, they
      efficiently induced diabetes, irrespective of treatment with IL-27 prior to
      transfer into RIP-mOVA mice. These findings suggest that use of IL-27 to modulate
      autoimmune diseases might have limited therapeutic efficacy if autoaggressive
      Tc17 cells have already developed.

PMID- 25070085
TI  - Fast online corrections of tripping responses.
AB  - Tripping over obstacles is one of the main causes of falls. One potential hazard
      to actually fall when tripped is inadequate foot landing. Adequate landing is
      required to control the body's angular momentum, while avoiding dangerous
      surfaces (slippery patch, uneven ground). To avoid such dangers, foot trajectory
      needs to be controlled by inhibiting and adjusting the initiated recovery foot
      path during a tripping reaction. We investigated whether such adjustments can be
      made without jeopardizing balance recovery. Sixteen healthy young adults (25.1 +/
      3.2 years) walked at their comfortable speed over a walkway equipped with 14
      hidden obstacles. Participants were tripped 10 times in between a random number
      of normal walking trials; five trips included a projection of a forbidden zone
      (FZ, 30 * 50 cm) at the subject's preferred landing position. Participants were
      instructed to land their recovery foot outside the FZ, if the FZ was presented.
      Responses were evaluated in terms of foot position and body angular momentum at
      and following recovery foot landing. Participants successfully landed their
      recovery foot outside the FZ in 80% of trials, using strategies of either
      shortening their recovery steps (84%) or side stepping (16%). Their performance
      improved over trials, and some participants switched strategies. Angular momenta
      of the adjusted steps remained small at and following recovery foot landing.
      Young adults can quickly change foot trajectory after tripping by using different
      strategies, and without detrimental consequences on balance recovery, in terms of
      the angular momentum. These results open possibilities for training of tripping
      reactions.

PMID- 25070086
TI  - The influence of target object shape on maximum grip aperture in human grasping
      movements.
AB  - The shape of a target object could influence maximum grip aperture in human
      grasping movements in several different ways. Maximum grip aperture could be
      influenced by the required precision of digit placement, by the aim to avoid
      colliding with the wrong parts of the target objects, by the mass of the target
      objects, or by (mis)judging the width or the volume of the target objects. To
      examine the influence of these five factors, we asked subjects to grasp five
      differently shaped target objects with the same maximal width, height and depth
      and compared their maximum grip aperture with what one would expect for each of
      the five factors. The five target objects, a cube, a three-dimensional plus sign,
      a rectangular block, a cylinder and a sphere, were all grasped with the same
      final grip aperture. The experimentally observed maximum grip apertures
      correlated poorly with the maximum grip apertures that were expected on the basis
      of the required precision, the actual mass, the perceived width and the perceived
      volume. They correlated much better with the maximum grip apertures that were
      expected on the basis of avoiding unintended collisions with the target object.
      We propose that the influence of target object shape on maximum grip aperture
      might primarily be the result of the need to avoid colliding with the wrong parts
      of the target object. 

PMID- 25070087
TI  - Giant uterine artery pseudoaneurysm after a missed miscarriage termination in a
      cesarean scar pregnancy.
AB  - BACKGROUND: Uterine artery pseudoaneurysms are dangerous and can lead to severe
      hemorrhage. We report an uncommon cause of a giant pseudoaneurysm in a missed
      miscarriage in a woman with a cesarean scar pregnancy. CASE PRESENTATION: The
      patient was a 25-year-old Chinese woman with a missed miscarriage in a cesarean
      scar pregnancy. Curettage was performed under ultrasound monitoring. A uterine
      artery pseudoaneurysm measuring 71 * 44 * 39 mm was detected the next day by
      Doppler ultrasonography. While waiting for admittance to an advanced institution
      to undergo embolization treatment, the pseudoaneurysm ruptured spontaneously. The
      subsequent severe hemorrhage necessitated hysterectomy. CONCLUSION: A delay in
      diagnosis of uterine artery pseudoaneurysms may result from a long period between
      the curettage and follow-up examination. Ultrasound and Doppler ultrasonography
      should be performed repeatedly at short intervals to rule out them, especially in
      cesarean scar pregnancies. For a giant uterine artery pseudoaneurysm,
      interventional embolization might be the first treatment choice. If time allows,
      intra-operative ligation of the feeding vessels should be attempted before any
      decision to perform a hysterectomy is made. However, hysterectomy remains a
      possibility when severe bleeding occurs.

PMID- 25070088
TI  - Preparation and immunogenicity of conjugate based on hydrazine-treated
      lipopolysaccharide antigen of Vibrio cholerae O139.
AB  - A glycoconjugate construct was based on attachment of V. cholerae O139 hydrazine
      treated lipopolysaccharide (LPS) to carboxylated bovine serum albumin (CBSA) via
      its amino group. The immunological properties of the glycoconjugate were tested
      using BALB/c mice, injected subcutaneously without any adjuvant three times at 2
      weeks interval. The immunogenicity of the conjugate was estimated by enzyme
      linked immunosorbent assay, testing of anti-LPS IgG, IgM, and IgA antibodies. The
      conjugate elicited a statistically significant increase of LPS-specific IgG
      levels in mice (p < 0.001). The specific anti-LPS IgG and IgA response after the
      second booster dose was significantly higher compared with reference and
      unconjugated detoxified LPS response. Antibodies elicited by the dLPS-CBSA
      conjugate were vibriocidal.

PMID- 25070089
TI  - Dangling ends perturb the stability of RNA duplexes responsive to surrounding
      conditions.
AB  - Unpaired terminal nucleotides (dangling ends) occur in various biologically
      important RNA structures. We studied the thermal stability of RNA duplexes with
      dangling ends under conditions that mimic those in cells. Dangling ends of one or
      two nucleotides stabilized a duplex up to approximately 2.7 kcal mol(-1) in the
      absence of cosolutes. RNA duplexes with dangling purine nucleotides were more
      stable than those with pyrimidine nucleotides. Interestingly, in the presence of
      various cosolutes, RNA duplexes with purine dangling ends were significantly
      destabilized, although those with pyrimidine dangling ends were destabilized
      slightly. For example, in 30 wt % poly(ethylene glycol), stabilization resulting
      from adenine dangling ends was reduced by 1.4 kcal mol(-1) . Our quantitative
      analyses also showed that the number of water molecules bound to the dangling
      ends in an aqueous solution was independent of the nucleotide type but dependent
      on the stability of the dangling-end region. It has been considered that dangling
      ends stabilize helices; however, our results suggest that the stabilization is
      responsive to the surrounding conditions.

PMID- 25070091
TI  - Pharmacokinetic interaction between pyronaridine-artesunate and metoprolol.
AB  - The objectives of this study were to characterize any drug-drug interaction
      between the antimalarial Pyramax (pyronaridine-artesunate [PA]) and the CYP2D6
      probe substrate metoprolol and to assess the safety of 60-day or 90-day PA
      redosing, particularly with regard to liver biochemistry parameters. Healthy
      adult subjects were randomized to arm A (n = 26) or arm B (n = 30), with the arm
      A subjects administered 100 mg metoprolol tartrate in the first period, 100 mg
      metoprolol tartrate with the third of three daily doses of PA in the second
      period, and three daily doses of PA alone in the 90-day redosing period. The arm
      B subjects received the three-day PA regimen in the first period, with redosing
      of the regimen after 60 days in the second period. The noncompartmental
      pharmacokinetic parameters were computed for metoprolol, its metabolite alpha
      hydroxymetoprolol, and pyronaridine. The coadministration of metoprolol and PA
      was associated with an average 47.93% (90% confidence interval [CI], 30.52,
      67.66) increase in the maximum concentration of metoprolol and a 25.60% (90% CI,
      15.78, 36.25) increase in the metoprolol area under the concentration-time curve
      from time zero to the last quantifiable concentration obtained (AUC0-t); these
      increases most likely resulted from pyronaridine-mediated CYP2D6 inhibition. No
      interaction effect of metoprolol with pyronaridine was apparent. Following dosing
      with PA, some subjects experienced rises in liver function tests above the upper
      limit of normal during the first few days following PA administration. All such
      elevations resolved typically within 10 days, and up to 30 days at most. In
      subjects who were redosed, the incidences of alanine aminotransferase (ALT) or
      aspartate transaminase (AST) level elevations were similar on the first and
      second administrations, with no marked difference between the 60-day and 90-day
      redosing. 

PMID- 25070090
TI  - Tn5253 family integrative and conjugative elements carrying mef(I) and catQ
      determinants in Streptococcus pneumoniae and Streptococcus pyogenes.
AB  - The linkage between the macrolide efflux gene mef(I) and the chloramphenicol
      inactivation gene catQ was first described in Streptococcus pneumoniae (strain
      Spn529), where the two genes are located in a module designated IQ element.
      Subsequently, two different defective IQ elements were detected in Streptococcus
      pyogenes (strains Spy029 and Spy005). The genetic elements carrying the three IQ
      elements were characterized, and all were found to be Tn5253 family integrative
      and conjugative elements (ICEs). The ICE from S. pneumoniae (ICESpn529IQ) was
      sequenced, whereas the ICEs from S. pyogenes (ICESpy029IQ and ICESpy005IQ, the
      first Tn5253-like ICEs reported in this species) were characterized by PCR
      mapping, partial sequencing, and restriction analysis. ICESpn529IQ and
      ICESpy029IQ were found to share the intSp 23FST81 integrase gene and an identical
      Tn916 fragment, whereas ICESpy005IQ has int5252 and lacks Tn916. All three ICEs
      were found to lack the linearized pC194 plasmid that is usually associated with
      Tn5253-like ICEs, and all displayed a single copy of a toxin-antitoxin operon
      that is typically contained in the direct repeats flanking the excisable pC194
      region when this region is present. Two different insertion sites of the IQ
      elements were detected, one in ICESpn529IQ and ICESpy029IQ, and another in
      ICESpy005IQ. The chromosomal integration of the three ICEs was site specific,
      depending on the integrase (intSp 23FST81 or int5252). Only ICESpy005IQ was
      excised in circular form and transferred by conjugation. By transformation,
      mef(I) and catQ were cotransferred at a high frequency from S. pyogenes Spy005
      and at very low frequencies from S. pneumoniae Spn529 and S. pyogenes Spy029. 

PMID- 25070092
TI  - Susceptibility and diversity in the therapy-refractory genus scedosporium.
AB  - Scedosporium species show decreased susceptibility to the majority of systemic
      antifungal drugs. Acquired resistance is likely to disseminate differentially
      with the mode of exchange of genetic material between lineages. Inter- and
      intraspecific diversities of Scedosporium species were analyzed for three
      partitions (rDNA internal transcribed spacer gene [ITS], partial beta-tubulin
      gene, and amplified fragment length polymorphism profiles), with the aim to
      establish distribution of resistance between species, populations, and strains.
      Heterogeneity of and recombination between lineages were determined, and
      distances between clusters were calculated using a centroid approach. Clinical,
      geographic, and antifungal data were plotted on diversity networks. Scedosporium
      minutisporum, Scedosporium desertorum, and Scedosporium aurantiacum were
      distinguished unambiguously in all partitions and had differential antifungal
      susceptibility profiles (ASP). Pseudallescheria fusoidea and Pseudallescheria
      ellipsoidea were indistinguishable from Scedosporium boydii. Pseudallescheria
      angusta took an intermediate position between Scedosporium apiospermum and S.
      boydii. Scedosporium boydii and S. apiospermum had identical ASP. Differences in
      (multi)resistance were linked to individual strains. S. apiospermum and S. boydii
      showed limited interbreeding and were recognized as valid, sympatric species. The
      S. apiospermum/S. boydii group, comprising the main clinically relevant
      Scedosporium species, consists of separate lineages and is interpreted as a
      complex undergoing sympatric evolution with incomplete lineage sorting. In
      routine diagnostics, the lineages in S. apiospermum/S. boydii are indicated with
      the umbrella descriptor "S. apiospermum complex"; individual species can be
      identified with rDNA ITS with 96.3% confidence. Voriconazole is recommended as
      the first-line treatment; resistance against this compound is rare. 

PMID- 25070094
TI  - A replicate designed bioequivalence study to compare two fixed-dose combination
      products of artesunate and amodiaquine in healthy chinese volunteers.
AB  - Artesun-Plus is a fixed-dose combination antimalarial agent containing artesunate
      and amodiaquine. The current study was conducted to compare the pharmacokinetic
      and safety profiles of Artesun-Plus and the WHO-designated comparator product
      Artesunate Amodiaquine Winthrop. To overcome the high intrasubject variability of
      artesunate, the study applied a two-sequence and four-period crossover (2 by 4),
      replicate study design to assess bioequivalence between the two products in 31
      healthy male Chinese volunteers under fasting conditions. The results showed that
      the values of the geometric mean ratios of maximum concentration of drug in
      plasma (Cmax) and area under the concentration-time curve from time zero to the
      last blood sample collection (AUC0-last) for the artesunate component in the test
      and reference products were 95.9% and 93.9%, respectively, and that the
      corresponding 90% confidence intervals were 84.5% to 108.7% and 87.2% to 101.1%,
      while the geometric mean ratios for the amodiaquine component in the test and
      reference products were 95.0% and 100.0%, respectively, and the corresponding 90%
      confidence intervals were 86.7% to 104.1% and 93.5% to 107.0%. In conclusion,
      bioequivalence between the two artesunate and amodiaquine fixed-dose combination
      products was demonstrated for both components. The study also confirmed high
      intrasubject variability, especially for artesunate: the coefficients of
      variation (CV) of Cmax values for the test and reference products were 39.2% and
      43.7%, respectively, while those for amodiaquine were 30.6% and 30.2%,
      respectively. 

PMID- 25070093
TI  - Sigma S-dependent antioxidant defense protects stationary-phase Escherichia coli
      against the bactericidal antibiotic gentamicin.
AB  - Stationary-phase bacteria are important in disease. The sigma(s)-regulated
      general stress response helps them become resistant to disinfectants, but the
      role of sigma(s) in bacterial antibiotic resistance has not been elucidated. Loss
      of sigma(s) rendered stationary-phase Escherichia coli more sensitive to the
      bactericidal antibiotic gentamicin (Gm), and proteomic analysis suggested
      involvement of a weakened antioxidant defense. Use of the psfiA genetic reporter,
      3'-(p-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm
      generated more reactive oxygen species (ROS) in the mutant. HPF measurements can
      be distorted by cell elongation, but Gm did not affect stationary-phase cell
      dimensions. Coadministration of the antioxidant N-acetyl cysteine (NAC) decreased
      drug lethality particularly in the mutant, as did Gm treatment under anaerobic
      conditions that prevent ROS formation. Greater oxidative stress, due to
      insufficient quenching of endogenous ROS and/or respiration-linked electron
      leakage, therefore contributed to the greater sensitivity of the mutant;
      infection by a uropathogenic strain in mice showed this to be the case also in
      vivo. Disruption of antioxidant defense by eliminating the quencher proteins,
      SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and
      TalA, which provide NADPH for ROS decomposition, also generated greater oxidative
      stress and killing by Gm. Thus, besides its established mode of action, Gm also
      kills stationary-phase bacteria by generating oxidative stress, and targeting the
      antioxidant defense of E. coli can enhance its efficacy. Relevant aspects of the
      current controversy on the role of ROS in killing by bactericidal drugs of
      exponential-phase bacteria, which represent a different physiological state, are
      discussed. 

PMID- 25070095
TI  - Pivotal role for a tail subunit of the RNA polymerase II mediator complex CgMed2
      in azole tolerance and adherence in Candida glabrata.
AB  - Antifungal therapy failure can be associated with increased resistance to the
      employed antifungal agents. Candida glabrata, the second most common cause of
      invasive candidiasis, is intrinsically less susceptible to the azole class of
      antifungals and accounts for 15% of all Candida bloodstream infections. Here, we
      show that C. glabrata MED2 (CgMED2), which codes for a tail subunit of the RNA
      polymerase II Mediator complex, is required for resistance to azole antifungal
      drugs in C. glabrata. An inability to transcriptionally activate genes encoding a
      zinc finger transcriptional factor, CgPdr1, and multidrug efflux pump, CgCdr1,
      primarily contributes to the elevated susceptibility of the Cgmed2Delta mutant
      toward azole antifungals. We also report for the first time that the Cgmed2Delta
      mutant exhibits sensitivity to caspofungin, a constitutively activated protein
      kinase C-mediated cell wall integrity pathway, and elevated adherence to
      epithelial cells. The increased adherence of the Cgmed2Delta mutant was
      attributed to the elevated expression of the EPA1 and EPA7 genes. Further, our
      data demonstrate that CgMED2 is required for intracellular proliferation in human
      macrophages and modulates survival in a murine model of disseminated candidiasis.
      Lastly, we show an essential requirement for CgMed2, along with the Mediator
      middle subunit CgNut1 and the Mediator cyclin-dependent kinase/cyclin subunit
      CgSrb8, for the high-level fluconazole resistance conferred by the hyperactive
      allele of CgPdr1. Together, our findings underscore a pivotal role for CgMed2 in
      basal tolerance and acquired resistance to azole antifungals. 

PMID- 25070096
TI  - Whole-genome assembly of Klebsiella pneumoniae coproducing NDM-1 and OXA-232
      carbapenemases using single-molecule, real-time sequencing.
AB  - The whole-genome sequence of a carbapenem-resistant Klebsiella pneumoniae strain,
      PittNDM01, which coproduces NDM-1 and OXA-232 carbapenemases, was determined in
      this study. The use of single-molecule, real-time (SMRT) sequencing provided a
      closed genome in a single sequencing run. K. pneumoniae PittNDM01 has a single
      chromosome of 5,348,284 bp and four plasmids: pPKPN1 (283,371 bp), pPKPN2
      (103,694 bp), pPKPN3 (70,814 bp), and pPKPN4 (6,141 bp). The contents of the
      chromosome were similar to that of the K. pneumoniae reference genome strain MGH
      78578, with the exception of a large inversion spanning 23.3% of the chromosome.
      In contrast, three of the four plasmids are unique. The plasmid pPKPN1, an
      IncHI1B-like plasmid, carries the blaNDM-1, armA, and qnrB1 genes, along with
      tellurium and mercury resistance operons. blaNDM-1 is carried on a unique
      structure in which Tn125 is further bracketed by IS26 downstream of a class 1
      integron. The IncFIA-like plasmid pPKPN3 also carries an array of resistance
      elements, including blaCTX-M-15 and a mercury resistance operon. The ColE-type
      plasmid pPKPN4 carrying blaOXA-232 is identical to a plasmid previously reported
      from France. SMRT sequencing was useful in resolving the complex bacterial
      genomic structures in the de novo assemblies. 

PMID- 25070097
TI  - Population pharmacokinetics of abacavir in pregnant women.
AB  - For the first time, a population approach was used to describe abacavir (ABC)
      pharmacokinetics in HIV-infected pregnant and nonpregnant women. A total of 266
      samples from 150 women were obtained. No covariate effect (from age, body weight,
      pregnancy, or gestational age) on ABC pharmacokinetics was found. Thus, it seems
      unnecessary to adapt the ABC dosing regimen during pregnancy. 

PMID- 25070098
TI  - Sequence types 235, 111, and 132 predominate among multidrug-resistant
      pseudomonas aeruginosa clinical isolates in Croatia.
AB  - A population analysis of 103 multidrug-resistant Pseudomonas aeruginosa isolates
      from Croatian hospitals was performed. Twelve sequence types (STs) were
      identified, with a predominance of international clones ST235 (serotype O11
      [41%]), ST111 (serotype O12 [15%]), and ST132 (serotype O6 [11%]). Overexpression
      of the natural AmpC cephalosporinase was common (42%), but only a few ST235 or
      ST111 isolates produced VIM-1 or VIM-2 metallo-beta-lactamases or PER-1 or GES-7
      extended-spectrum beta-lactamases. 

PMID- 25070099
TI  - Randomized controlled trial comparing 7-day triple, 10-day sequential, and 7-day
      concomitant therapies for Helicobacter pylori infection.
AB  - With the rising prevalence of antimicrobial resistance, the failure rate of the
      standard triple therapy for Helicobacter pylori infection is increasing.
      Sequential therapy and concomitant therapy have been recommended to replace
      standard triple therapy for H. pylori eradication in regions with high
      clarithromycin resistance. The aim of this prospective, randomized, and
      controlled study was to simultaneously assess the efficacies of 10-day sequential
      and 7-day concomitant therapies versus a 7-day standard triple therapy for
      treating H. pylori infection. Consecutive H. pylori-infected subjects were
      randomly assigned to a 7-day standard triple therapy (pantoprazole,
      clarithromycin, and amoxicillin for 7 days), a 10-day sequential therapy
      (pantoprazole and amoxicillin for 5 days, followed by pantoprazole,
      clarithromycin, and metronidazole for a further 5 days), or a 7-day quadruple
      therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole for 7
      days). H. pylori status was confirmed 6 weeks after therapy. Three hundred seven
      H. pylori-infected participants were randomized to receive triple (n = 103),
      sequential (n = 102), or concomitant (n = 102) therapies. The eradication rates
      by an intention-to-treat analysis in the three treatment groups were 81.6% (95%
      confidence interval [CI], 74.1% to 89.0%), 89.2% (95% CI, 83.2% to 95.2%), and
      94.1% (95% CI, 89.5% to 98.7%). The seven-day concomitant therapy had a higher
      eradication rate than did the 7-day triple therapy (difference, 12.5%; 95% CI,
      3.7% to 21.3%). There were no significant differences in the eradication rates
      between the sequential and standard triple therapies. All three treatments
      exhibited similar frequencies of adverse events (8.7%, 8.8%, and 13.7%,
      respectively) and drug compliance (99.0%, 98.0%, and 100.0%, respectively). In
      conclusion, the seven-day concomitant therapy is superior to the 7-day standard
      triple therapy for H. pylori eradication. Additionally, it is less complex than
      the 10-day sequential therapy because the drugs are not changed halfway through
      the treatment course. (This study has been registered at ClinicalTrials.gov under
      registration no. NCT1769365.). 

PMID- 25070100
TI  - Effects of rifampin and ketoconazole on pharmacokinetics of morinidazole in
      healthy chinese subjects.
AB  - Morinidazole, a 5-nitroimidazole antimicrobial drug, has been approved for the
      treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections in
      China. It was reported that drug-drug interaction happened after the
      coadministration of ornidazole, an analog of morinidazole, and rifampin or
      ketoconazole. Therefore, we measured the plasma pharmacokinetics (PK) of
      morinidazole and its metabolites in the healthy Chinese volunteers prior to and
      following the administration of rifampin or ketoconazole using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The area under the
      concentration-time curve from time 0 to time t (AUC0-t) and maximum concentration
      in serum (Cmax) of morinidazole were decreased by 28% and 23%, respectively,
      after 6 days of exposure to 600 mg of rifampin once daily; the Cmaxs of N(+)
      glucuronides were increased by 14%, while their AUC0-ts were hardly changed.
      After 7 days of exposure to 200 mg of ketoconazole once daily, the AUC0-t and
      Cmax of the parent drug were not affected significantly. Cmaxs of N(+)
      glucuronides were decreased by 23%; AUC0-ts were decreased by 14%. The exposure
      of sulfate conjugate was hardly changed after the coadministration of rifampin or
      ketoconazole. Using recombinant enzyme of UGT1A9 and human hepatocytes, the
      mechanism of the altered PK behaviors of morinidazole and its metabolites was
      investigated. In human hepatocytes, ketoconazole dose dependently inhibited the
      formation of N(+)-glucuronides (50% inhibitory concentration [IC50], 1.5 MUM),
      while rifampin induced the mRNA level of UGT1A9 by 28% and the activity of UGT1A9
      by 53%. In conclusion, the effects of rifampin and ketoconazole on the plasma
      exposures of morinidazole and N(+)-glucuronide are less than 50%; therefore,
      rifampin and ketoconazole have little clinical significance in the
      pharmacokinetics of morinidazole. 

PMID- 25070101
TI  - In vivo activity of cefquinome against Escherichia coli in the thighs of
      neutropenic mice.
AB  - Cefquinome is a cephalosporin with broad-spectrum antibacterial activity,
      including activity against enteric Gram-negative bacilli such as Escherichia
      coli. We utilized a neutropenic mouse model of colibacillosis to examine the
      pharmacodynamic (PD) characteristics of cefquinome, as measured by organism
      number in homogenized thigh cultures after 24 h of therapy. Serum drug levels
      following 4-fold-escalating single doses of cefquinome were measured by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic (PK)
      properties of cefquinome were linear over a dose range of 10 to 640 mg/kg of body
      weight. Serum half-lives ranged from 0.29 to 0.32 h. Dose fractionation studies
      over a 24-h dose range of 2.5 to 320 mg/kg were conducted every 3, 6, 12, or 24
      h. Nonlinear regression analysis was used to determine which pharmacodynamic
      parameter best correlated with efficacy. The free percentage of the dosing
      interval that the serum levels exceed the MIC (fT>MIC) was the PK-PD index that
      best correlated with efficacy (R(2) = 73% for E. coli, compared with 13% for the
      maximum concentration of the free drug in serum [fCmax]/MIC and 45% for the free
      drug area under the concentration-time curve from 0 to 24 h [fAUC0-24]/MIC).
      Subsequently, we employed a similar dosing strategy by using 4-fold-increasing
      total cefquinome doses administered every 4 h to treat animals infected with four
      additional E. coli isolates. A sigmoid maximum-effect (Emax) model was used to
      estimate the magnitudes of the %fT>MIC associated with net bacterial stasis, a 1
      log10 CFU reduction from baseline, and a 2-log10 CFU reduction from baseline; the
      corresponding values were 28.01% +/- 2.27%, 37.23% +/- 4.05%, and 51.69% +/-
      9.72%. The potent bactericidal activity makes cefquinome an attractive option for
      the treatment of infections caused by E. coli. 

PMID- 25070103
TI  - Efficacy of PTX3 and posaconazole combination in a rat model of invasive
      pulmonary aspergillosis.
AB  - Posaconazole is currently used for the prophylaxis of invasive pulmonary
      aspergillosis (IPA). Limitations to posaconazole usage are drug-drug interactions
      and side effects. PTX3 is an innate immunity glycoprotein with opsonic activity,
      proven to be protective in IPA animal models. This study investigated the
      combination of posaconazole with PTX3. The results indicate synergy between PTX3
      and posaconazole against aspergillosis, suggesting that a combination of reduced
      doses of posaconazole with the immune response enhancer PTX3 might represent a
      treatment option with a higher therapeutic index than posaconazole. 

PMID- 25070102
TI  - Extensively drug-resistant pseudomonas aeruginosa isolates containing blaVIM-2
      and elements of Salmonella genomic island 2: a new genetic resistance determinant
      in Northeast Ohio.
AB  - Carbapenems are a mainstay of treatment for infections caused by Pseudomonas
      aeruginosa. Carbapenem resistance mediated by metallo-beta-lactamases (MBLs)
      remains uncommon in the United States, despite the worldwide emergence of this
      group of enzymes. Between March 2012 and May 2013, we detected MBL-producing P.
      aeruginosa in a university-affiliated health care system in northeast Ohio. We
      examined the clinical characteristics and outcomes of patients, defined the
      resistance determinants and structure of the genetic element harboring the blaMBL
      gene through genome sequencing, and typed MBL-producing P. aeruginosa isolates
      using pulsed-field gel electrophoresis (PFGE), repetitive sequence-based PCR (rep
      PCR), and multilocus sequence typing (MLST). Seven patients were affected that
      were hospitalized at three community hospitals, a long-term-care facility, and a
      tertiary care center; one of the patients died as a result of infection. Isolates
      belonged to sequence type 233 (ST233) and were extensively drug resistant (XDR),
      including resistance to all fluoroquinolones, aminoglycosides, and beta-lactams;
      two isolates were nonsusceptible to colistin. The blaMBL gene was identified as
      blaVIM-2 contained within a class 1 integron (In559), similar to the cassette
      array previously detected in isolates from Norway, Russia, Taiwan, and Chicago,
      IL. Genomic sequencing and assembly revealed that In559 was part of a novel 35-kb
      region that also included a Tn501-like transposon and Salmonella genomic island 2
      (SGI2)-homologous sequences. This analysis of XDR strains producing VIM-2 from
      northeast Ohio revealed a novel recombination event between Salmonella and P.
      aeruginosa, heralding a new antibiotic resistance threat in this region's health
      care system. 

PMID- 25070104
TI  - Crystal structure of the extended-spectrum beta-lactamase PER-2 and insights into
      the role of specific residues in the interaction with beta-lactams and beta
      lactamase inhibitors.
AB  - PER-2 belongs to a small (7 members to date) group of extended-spectrum beta
      lactamases. It has 88% amino acid identity with PER-1 and both display high
      catalytic efficiencies toward most beta-lactams. In this study, we determined the
      X-ray structure of PER-2 at 2.20 A and evaluated the possible role of several
      residues in the structure and activity toward beta-lactams and mechanism-based
      inhibitors. PER-2 is defined by the presence of a singular trans bond between
      residues 166 to 167, which generates an inverted Omega loop, an expanded fold of
      this domain that results in a wide active site cavity that allows for efficient
      hydrolysis of antibiotics like the oxyimino-cephalosporins, and a series of
      exclusive interactions between residues not frequently involved in the
      stabilization of the active site in other class A beta-lactamases. PER beta
      lactamases might be included within a cluster of evolutionarily related enzymes
      harboring the conserved residues Asp136 and Asn179. Other signature residues that
      define these enzymes seem to be Gln69, Arg220, Thr237, and probably Arg/Lys240A
      ("A" indicates an insertion according to Ambler's scheme for residue numbering in
      PER beta-lactamases), with structurally important roles in the stabilization of
      the active site and proper orientation of catalytic water molecules, among
      others. We propose, supported by simulated models of PER-2 in combination with
      different beta-lactams, the presence of a hydrogen-bond network connecting Ser70
      Gln69-water-Thr237-Arg220 that might be important for the proper activity and
      inhibition of the enzyme. Therefore, we expect that mutations occurring in these
      positions will have impacts on the overall hydrolytic behavior. 

PMID- 25070105
TI  - Relationship between ceftolozane-tazobactam exposure and selection for
      Pseudomonas aeruginosa resistance in a hollow-fiber infection model.
AB  - It is important to understand the relationship between antibiotic exposure and
      the selection of drug resistance in the context of therapy exposure. We sought to
      identify the ceftolozane-tazobactam exposure necessary to prevent the
      amplification of drug-resistant bacterial subpopulations in a hollow-fiber
      infection model. Two Pseudomonas aeruginosa challenge isolates were selected for
      study, a wild-type ATCC strain (ceftolozane-tazobactam MIC, 0.5 mg/liter) and a
      clinical isolate (ceftolozane-tazobactam MIC, 4 mg/liter). The experiment
      duration was 10 days, and the ceftolozane-tazobactam dose ratio (2:1) and dosing
      interval (every 8 h) were selected to approximate those expected to be used
      clinically. The studied ceftolozane-tazobactam dosing regimens ranged from
      62.5/31.25 to 2,000/1,000 mg per dose in step fold dilutions. Negative-control
      arms included no treatment and tazobactam at 500 mg every 8 h. Positive-control
      arms included ceftolozane at 1 g every 8 h and piperacillin-tazobactam dosed at
      4.5 g every 6 h. For the wild-type ATCC strain, resistance was not selected by
      any ceftolozane-tazobactam regimen evaluated. For the clinical isolate, an
      inverted-U-shaped function best described the relationship between the
      amplification of a drug-resistant subpopulation and drug exposure. The least
      (62.5/31.25 mg) and most (2,000/1,000 mg) intensive ceftolozane-tazobactam dosing
      regimens did not select for drug resistance. Drug resistance selection was
      observed with intermediately intensive dosing regimens (125/62.5 through
      1,000/500 mg). For the intermediately intensive ceftolozane-tazobactam dosing
      regimens, the duration until the selection for drug resistance increased with
      dose regimen intensity. These data support the selection of ceftolozane
      tazobactam dosing regimens that minimize the potential for on-therapy drug
      resistance selection. 

PMID- 25070106
TI  - Biochemical and antiparasitic properties of inhibitors of the Plasmodium
      falciparum calcium-dependent protein kinase PfCDPK1.
AB  - PfCDPK1 is a Plasmodium falciparum calcium-dependent protein kinase, which has
      been identified as a potential target for novel antimalarial chemotherapeutics.
      In order to further investigate the role of PfCDPK1, we established a high
      throughput in vitro biochemical assay and used it to screen a library of over
      35,000 small molecules. Five chemical series of inhibitors were initially
      identified from the screen, from which series 1 and 2 were selected for chemical
      optimization. Indicative of their mechanism of action, enzyme inhibition by these
      compounds was found to be sensitive to both the ATP concentration and
      substitution of the amino acid residue present at the "gatekeeper" position at
      the ATP-binding site of the enzyme. Medicinal chemistry efforts led to a series
      of PfCDPK1 inhibitors with 50% inhibitory concentrations (IC50s) below 10 nM
      against PfCDPK1 in a biochemical assay and 50% effective concentrations (EC50s)
      less than 100 nM for inhibition of parasite growth in vitro. Potent inhibition
      was combined with acceptable absorption, distribution, metabolism, excretion, and
      toxicity (ADMET) properties and equipotent inhibition of Plasmodium vivax CDPK1.
      However, we were unable to correlate biochemical inhibition with parasite growth
      inhibition for this series overall. Inhibition of Plasmodium berghei CDPK1
      correlated well with PfCDPK1 inhibition, enabling progression of a set of
      compounds to in vivo evaluation in the P. berghei rodent model for malaria. These
      chemical series have potential for further development as inhibitors of CDPK1. 

PMID- 25070107
TI  - In vivo effect of quaternized chitosan-loaded polymethylmethacrylate bone cement
      on methicillin-resistant Staphylococcus epidermidis infection of the tibial
      metaphysis in a rabbit model.
AB  - Infection of open tibial fractures with contamination remains a challenge for
      orthopedic surgeons. Local use of antibiotic-impregnated polymethylmethacrylate
      (PMMA) beads and blocks is a widely used procedure to reduce the risk of
      infection. However, the development of antibiotic-resistant organisms make the
      management of infection more difficult. Our in vitro study demonstrated that
      quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan [HACC])
      loaded PMMA bone cement exhibits strong antibacterial activity toward antibiotic
      resistant bacteria. Therefore, the present study aimed to investigate the in vivo
      antibacterial activity of quaternized chitosan-loaded PMMA. Twenty-four adult
      female New Zealand White rabbits were used in this study. The right proximal
      tibial metaphyseal cavity was prepared, 10(7) CFU of methicillin-resistant
      Staphylococcus epidermidis was inoculated, and PMMA-only, gentamicin-loaded PMMA
      (PMMA-G), chitosan-loaded PMMA (PMMA-C), or HACC-loaded PMMA (PMMA-H) bone cement
      cylinders were inserted. During the follow-up period, the infections were
      evaluated using X rays on days 21 and 42 and histopathological and
      microbiological analyses on day 42 after surgery. Radiographic indications of
      bone infections, including bone lysis, periosteal reactions, cyst formation, and
      sequestral bone formation, were evident in the PMMA, PMMA-G, and PMMA-C groups
      but not in the PMMA-H group. The radiographic scores and gross bone pathological
      and histopathological scores were significantly lower in the PMMA-H group than in
      the PMMA, PMMA-G, and PMMA-C groups (P < 0.05). Explant cultures also indicated
      significantly less bacterial growth in the PMMA-H group than in the PMMA, PMMA-G,
      and PMMA-C groups (P < 0.01). We concluded that PMMA-H bone cement can inhibit
      the development of bone infections in this animal model inoculated with
      antibiotic-resistant bacteria, thereby demonstrating its potential application
      for treatment of local infections in open fractures. 

PMID- 25070108
TI  - Interaction of Interferon gamma-induced reactive oxygen species with ceftazidime
      leads to synergistic killing of intracellular Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei, a facultative intracellular pathogen, causes severe
      infections and is inherently refractory to many antibiotics. Previous studies
      from our group have shown that interferon gamma (IFN-gamma) interacts
      synergistically with the antibiotic ceftazidime to kill bacteria in infected
      macrophages. The present study aimed to identify the underlying mechanism of that
      interaction. We first showed that blocking reactive oxygen species (ROS) pathways
      reversed IFN-gamma- and ceftazidime-mediated killing, which led to our hypothesis
      that IFN-gamma-induced ROS interacted with ceftazidime to synergistically kill
      Burkholderia bacteria. Consistent with this hypothesis, we also observed that
      buthionine sulfoximine (BSO), another inducer of ROS, could substitute for IFN
      gamma to similarly potentiate the effect of ceftazidime on intracellular killing.
      Next, we observed that IFN-gamma induced ROS-mediated killing of intracellular
      but not extracellular bacteria. On the other hand, ceftazidime effectively
      reduced extracellular bacteria but was not capable of intracellular killing when
      applied at 10 MUg/ml. We investigated the exact role of IFN-gamma-induced ROS
      responses on intracellular bacteria and notably observed a lack of actin
      polymerization associated with Burkholderia bacteria in IFN-gamma-treated
      macrophages, which led to our finding that IFN-gamma-induced ROS blocks vacuolar
      escape. Based on these results, we propose a model in which synergistically
      reduced bacterial burden is achieved primarily through separate and
      compartmentalized killing: intracellular killing by IFN-gamma-induced ROS
      responses and extracellular killing by ceftazidime. Our findings suggest a means
      of enhancing antibiotic activity against Burkholderia bacteria through
      combination with drugs that induce ROS pathways or otherwise target intracellular
      spread and/or replication of bacteria. 

PMID- 25070109
TI  - Reduced in vitro doxycycline susceptibility in plasmodium falciparum field
      isolates from Kenya is associated with PfTetQ KYNNNN sequence polymorphism.
AB  - Doxycycline is widely used for malaria prophylaxis by international travelers.
      However, there is limited information on doxycycline efficacy in Kenya, and
      genetic polymorphisms associated with reduced efficacy are not well defined. In
      vitro doxycycline susceptibility profiles for 96 Plasmodium falciparum field
      isolates from Kenya were determined. Genetic polymorphisms were assessed in P.
      falciparum metabolite drug transporter (Pfmdt) and P. falciparum GTPase tetQ
      (PftetQ) genes. Copy number variation of the gene and the number of KYNNNN amino
      acid motif repeats within the protein encoded by PftetQ were determined. Reduced
      in vitro susceptibility to doxycycline was defined by 50% inhibitory
      concentrations (IC50s) of >=35,000 nM. The odds ratio (OR) of having 2 PfTetQ
      KYNNNN amino acid repeats in isolates with IC50s of >35,000 nM relative to those
      with IC50s of <35,000 nM is 15 (95% confidence interval [CI], 3.0 to 74.3; P
      value of <0.0002). Isolates with 1 copy of the Pfmdt gene had a median IC50 of
      6,971 nM, whereas those with a Pfmdt copy number of >1 had a median IC50 of 9,912
      nM (P = 0.0245). Isolates with 1 copy of PftetQ had a median IC50 of 6,370 nM,
      whereas isolates with a PftetQ copy number of >1 had a median IC50 of 3,422 nM (P
      < 0.0007). Isolates with 2 PfTetQ KYNNNN motif repeats had a median IC50 of
      26,165 nM, whereas isolates with 3 PfTetQ KYNNNN repeats had a median IC50 of
      3,352 nM (P = 0.0023). PfTetQ sequence polymorphism is associated with a reduced
      doxycycline susceptibility phenotype in Kenyan isolates and is a potential marker
      for susceptibility testing. 

PMID- 25070110
TI  - Changing antimicrobial resistance profiles among Neisseria gonorrhoeae isolates
      in Italy, 2003 to 2012.
AB  - The emergence of Neisseria gonorrhoeae isolates displaying resistance to
      antimicrobial agents is a major public health concern and a serious issue related
      to the occurrence of further untreatable gonorrhea infections. A retrospective
      analysis on 1,430 N. gonorrhoeae isolates, collected from 2003 through 2012, for
      antimicrobial susceptibility by Etest and molecular characterization by Neisseria
      gonorrhoeae multiantigen sequence typing (NG-MAST) was carried out in Italy.
      Azithromycin-resistant gonococci decreased from 14% in 2007 to 2.2% in 2012.
      Similarly, isolates with high MICs to cefixime (>0.125 mg/liter) decreased from
      11% in 2008 to 3.3% in 2012. The ciprofloxacin resistance rate remains quite
      stable, following an increasing trend up to 64% in 2012. The percentage of
      penicillinase-producing N. gonorrhoeae (PPNG) significantly declined from 77% in
      2003 to 7% in 2012. A total of 81 multidrug-resistant (MDR) gonococci were
      identified, showing 11 different antimicrobial resistance patterns. These were
      isolated from men who have sex with men (MSM) and from heterosexual patients. Two
      sequence types (STs), ST661 and ST1407, were the most common. Genogroup 1407,
      which included cefixime-, ciprofloxacin-, and azithromycin-resistant isolates,
      was found. In conclusion, a change in the antimicrobial resistance profiles among
      gonococci was identified in Italy together with a percentage of MDR isolates. 

PMID- 25070111
TI  - Double mutation in the pfmdr1 gene is associated with emergence of chloroquine
      resistant Plasmodium falciparum malaria in Eastern India.
AB  - Malaria is a major public health problem in tropical and subtropical countries,
      including India. This study elucidates the cause of chloroquine treatment failure
      (for Plasmodium falciparum infection) before the introduction of artemisinin
      combination therapy. One hundred twenty-six patients were randomized to
      chloroquine treatment, and the therapeutic efficacy was monitored from days 1 to
      28. An in vitro susceptibility test was performed with all isolates. Parasitic
      DNA was isolated, followed by PCR and restriction digestion of different codons
      of the pfcrt gene (codons 72 to 76) and the pfmdr1 gene (N86Y, Y184F, S1034C,
      N1042D, and D1246Y). Finally, sequencing was done to confirm the mutations. Forty
      three (34.13%) early treatment failure cases and 16 (12.69%) late treatment
      failure cases were observed after chloroquine treatment. In vitro chloroquine
      resistance was found in 103 isolates (81.75%). Twenty-six (60.47%) early
      treatment failure cases and 6 (37.5%) late treatment failure cases were
      associated with the CVMNK-YYSNY allele (the underlined amino acids are those that
      were mutated). Moreover, the CVIEK-YYSNY allele was found in 8 early treatment
      failure (18.60%) and 2 late treatment failure (12.5%) cases. The presence of the
      wild-type pfcrt (CVMNK) and pfmdr1 (YYSNY) double mutant allele in chloroquine
      nonresponsive cases was quite uncommon. In vivo chloroquine treatment failure and
      in vitro chloroquine resistance were strongly correlated with the CVMNK-YYSNY and
      CVIEK-YYSNY haplotypes (P < 0.01). 

PMID- 25070112
TI  - Induction of mitochondrial dysfunction and oxidative stress in Leishmania
      donovani by orally active clerodane diterpene.
AB  - This study was performed to investigate the mechanistic aspects of cell death
      induced by a clerodane diterpene (K-09) in Leishmania donovani promastigotes that
      was previously demonstrated to be safe and orally active against visceral
      leishmaniasis (VL). K-09 caused depolarization of the mitochondrion and the
      generation of reactive oxygen species, triggering an apoptotic response in L.
      donovani promastigotes. Mitochondrial dysfunction subsequently resulted in the
      release of cytochrome c into the cytosol, impairing ATP production. Oxidative
      stress caused the depletion of reduced glutathione, while pretreatment with
      antioxidant N-acetyl cysteine (NAC) was able to abrogate oxidative stress.
      However, NAC failed to restore the mitochondrial membrane potential or
      intracellular calcium homeostasis after K-09 treatment, suggesting that the
      generation of oxidative stress is a downstream event relative to the other
      events. Caspase-3/-7-like protease activity and genomic DNA fragmentation were
      observed. Electron microscopy studies revealed gross morphological alterations
      typical of apoptosis, including severe mitochondrial damage, pyknosis of the
      nucleus, structural disruption of the mitochondrion-kinetoplast complex,
      flagellar pocket alterations, and the displacement of organelles. Moreover, an
      increased number of lipid droplets was detected after K-09 treatment, which is
      suggestive of altered lipid metabolism. Our results indicate that K-09 induces
      mitochondrial dysfunction and oxidative stress-mediated apoptotic cell death in
      L. donovani promastigotes, sharing many features with metazoan apoptosis. These
      mechanistic insights provide a basis for further investigation toward the
      development of K-09 as a potential drug candidate for VL. 

PMID- 25070113
TI  - In vivo study of the efficacy of the aromatic water of Zataria multiflora on
      hydatid cysts.
AB  - Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were
      employed to determine the chemical composition of the essential oil (EO) from
      aromatic water (AW) of Zataria multiflora. Thymol (66.9%), carvacrol (15.2%), and
      carvone (7.3%) were found to be the major EO constituents. Eighty laboratory
      BALB/c mice were infected intraperitoneally by injection of 1,500 viable
      protoscolices and were divided into prevention (40 mice) and therapeutic (40
      mice) groups. To prove the preventive effect of the Z. multiflora AW on
      development of hydatid cysts, the 40 infected mice were allocated into three
      treatment groups, including the albendazole group (10 mice that received 150
      mg/kg body weight/day for 10 days), the Z. multiflora AW group (15 mice that
      received 20 ml/liter in drinking water for 8 months), and a control group (15
      mice that received no treatment). To estimate the therapeutic effect of the Z.
      multiflora AW on the hydatid cyst, after 8 months of infection, the 15 remaining
      mice were allocated into three experimental treatment groups of five animals
      each, including the albendazole group (300 mg/kg/day for 20 days), Z. multiflora
      AW group (40 ml/liter in drinking water for 30 days), and control group (no
      treatment). All mice were then euthanized, and the sizes and weights of the cysts
      as well as their ultrastructural changes were investigated. The weights and sizes
      of the hydatid cysts significantly decreased upon treatment with the Z.
      multiflora AW in both the preventive and therapeutic groups (P < 0.05). The
      results of scanning electron microscopy also showed considerable damage in the
      germinal layer of the hydatid cysts recovered from the treated animals. 

PMID- 25070114
TI  - Optimized MEGA-SPECIAL for in vivo glutamine detection in the rat brain at 14.1
      T.
AB  - Glutamine has multiple roles in brain metabolism and its concentration can be
      altered in various pathological conditions. An accurate knowledge of its
      concentration is therefore highly desirable to monitor and study several brain
      disorders in vivo. However, in recent years, several MRS studies have reported
      conflicting glutamine concentrations in the human brain. A recent hypothesis for
      explaining these discrepancies is that a short T2 component of the glutamine
      signal may impact on its quantification at long echo times. The present study
      therefore aimed to investigate the impact of acquisition parameters on the
      quantified glutamine concentration using two different acquisition techniques,
      SPECIAL at ultra-short echo time and MEGA-SPECIAL at moderate echo time. For this
      purpose, MEGA-SPECIAL was optimized for the first time for glutamine detection.
      Based on the very good agreement of the glutamine concentration obtained between
      the two measurements, it was concluded that no impact of a short T2 component of
      the glutamine signal was detected.

PMID- 25070115
TI  - Successful autotransplantation of a mature mesiodens to replace a traumatized
      maxillary central incisor.
AB  - AIM: This case describes the successful transplantation of a mature mesiodens
      tooth to replace a traumatized maxillary central incisor. SUMMARY: A 17-year-old
      male attended 1 week after a traumatic injury to his left maxillary central
      incisor (tooth 21). Radiographs revealed a horizontal root fracture and a poor
      prognosis. The tooth was atraumatically removed and replaced with a mesiodens
      lying in the same region. After stabilization, root canal treatment was performed
      and aesthetics were restored with a tooth coloured restoration. A 2-year follow
      up revealed the tooth had good aesthetics and function. KEY LEARNING POINTS: A
      supernumerary nonfunctional tooth such as a mesiodens can be successfully used to
      replace a missing permanent tooth by autotransplantation. Autotransplantation has
      a high success rate if case selection is good, appropriate surgery is carried out
      and excellent hygiene is maintained. Autotransplantation should be considered as
      one of the most biologic techniques for replacing a missing tooth with minimal
      cost. Autotransplantation can be carried out even after complete root formation
      in the donor tooth.

PMID- 25070117
TI  - Current trends in surgical revascularization of multivessel coronary artery
      disease with arterial grafts.
AB  - It is well known that graft patency determines prognosis in coronary artery
      bypass grafting. Numerous reports over the past 20 years have documented superior
      patency and prognosis when multiple arterial grafts are used. The use of the left
      internal thoracic artery to graft the left anterior descending artery has been
      widely accepted as the gold standard for surgical treatment of coronary disease
      for over 40 years. A considerable body of evidence suggests that the right
      internal thoracic artery behaves in the same way. Radial artery grafts are being
      studied in several randomized trials, but observational studies suggest a
      performance comparing favorably with the saphenous vein. The right gastroepiploic
      artery has been recognized as a suitable and reliable conduit for coronary bypass
      surgery. However, the use of multiple other arterial grafts is performed in less
      than 10% of surgical procedures, probably because of perceptions of technical
      complexity, prolonged time for conduit harvesting, and increased perioperative
      complications. As a result, most patients with multivessel coronary artery
      disease do not benefit from extensive revascularization with arterial conduits.
      The aim of this review is to summarize the current evidence for the extensive use
      of arterial conduits in the revascularization of multivessel coronary artery
      disease. 

PMID- 25070116
TI  - Elevated soluble ST2 and depression increased the risk of all-cause mortality and
      hospitalization in patients with heart failure.
AB  - This study aimed to assess the predictive effect of soluble ST2 (sST2) and
      depressive symptoms in patients with heart failure (HF) and to determine whether
      the prognosis of HF patients with preserved ejection fraction (HFpEF) differs
      from those with reduced ejection fraction (HFrEF). A cohort of 233 HF patients
      was followed for 1 year. Depressive symptoms were evaluated by the Hospital
      Anxiety and Depression Scale. The primary endpoint was all-cause mortality and HF
      related hospitalization. For the analysis of survival, the left ventricular
      ejection fraction (LVEF) cut-offs for defining HFpEF were set at 50%, 45%, and
      40%, respectively. With increasing LVEF, levels of sST2 were gradually decreased
      (45.2 ng/mL, 35.8 ng/mL, and 32.1 ng/mL in patients with LVEF <= 40%, 41% to 49%,
      and >= 50%, respectively, P for trend < 0.001), as well as the prevalence of
      depressive symptoms (35.4%, 33.3%, and 20.4%, respectively, P for trend = 0.022).
      After 1-year follow-up, 128 patients (54.9%) achieved the primary endpoint and 47
      patients (20.2%) died. Depressive symptoms were independent risk factors of all
      cause mortality and HF-related hospitalization. The combined presence of elevated
      sST2 (> 36.0 ng/mL) and depressive symptoms was associated with a 4.9-fold
      increased risk of the primary endpoint. Regardless of LVEF cut-offs, the
      associated risk of adverse outcomes in HFpEF was as high as in HFrEF after
      adjustment for significant risk factors including sST2 and N-terminal pro-brain
      natriuretic peptide. In conclusion, depressive symptoms provided additional
      prognostic information to that of sST2 in HF patients. The prognosis of HFpEF
      patients was similar to that of HFrEF patients. 

PMID- 25070118
TI  - Simultaneously successful transfemoral aortic valve implantation and endovascular
      repair of thoracic aortic saccular aneurysm.
AB  - The prevalence of aortic stenosis (AS) increases in the elderly. They present
      high surgical risk due to comorbid factors that increase with age. Transcatheter
      aortic valve implantation (TAVI) is an effective method in patients who present
      with severe aortic stenosis with a higher surgical risk or who cannot undergo
      surgical aortic valve replacement (s-AVR). In our case, the presence of saccular
      thoracic aortic aneurysm with severe AS, which is a vital co-morbidity, requires
      the treatment of both. The rise in systolic pressure following the TAVI procedure
      increases the saccular thoracic aneurysm rupture risk and this is why the timing
      and method of the two treatments become crucial. In this case, which is as far as
      we know the fi rst and only report in the literature, both TAVI and endovascular
      thoracic aortic saccular aneurysm repair were applied simultaneously and
      successfully to the patient via the same transfemoral route. After 1 month, the
      patient had good functional capacity and there were no complications in control
      tomography and echocardiography. In this way, we attempted to emphasize with a
      multidisciplinary study that the patients be assessed carefully before the
      procedure, and found that even in patients with common peripheral vascular
      diseases, a transfemoral route could be used together with the proper methods,
      and that both procedures could be performed simultaneously. 

PMID- 25070119
TI  - Mother-child aspiration technique.
AB  - A 94-year-old woman underwent primary percutaneous coronary intervention for a
      total occlusion of the right coronary artery. A 6-Fr Ikari-left guiding catheter
      was inserted through the right radial artery. Initially, thrombectomy was
      performed with a conventional thrombus aspiration catheter. However, only small
      fragments of thrombus were aspirated and coronary blood flow was still
      obstructed. Subsequently, a 4.5-Fr straight guiding catheter was advanced through
      the 6-Fr guiding catheter into the coronary artery and aspiration was
      reinitiated. During the course of aspiration, the backflow of the blood was
      blocked. The inner catheter was pulled back slowly, maintaining suction. Just
      before it reached the tip of the 6-Fr guiding catheter, another vacuum syringe
      was attached to the side arm of the Y-connecter of the 6-Fr guiding catheter and
      additional aspiration with the outer guiding catheter was started. After complete
      retrieval of the 4.5-Fr catheter from the guiding catheter, thrombus was found in
      the vacuum syringes from both inner and outer guiding catheters. We consider that
      this double aspiration, with a mother-child catheter technique, is a simple and
      effective means of aspirating a larger thrombus, and may prevent the dislodgement
      of thrombus at the tip of the outer guiding catheter, which could cause systemic
      embolism. 

PMID- 25070120
TI  - Coronary artery spasm following off-pump coronary artery bypass surgery.
AB  - Coronary artery spasm after coronary artery bypass surgery may result in life
      threatening arrhythmias, circulatory collapse, or death. We report two cases of
      coronary artery spasm after coronary artery bypass surgery, one of which
      developed ventricular fibrillation requiring extracorporeal membrane oxygenation
      support. Both patients were discharged in good condition and are currently
      followed as outpatients. Unexpected sudden hemodynamic compromise could be due to
      coronary vasospasm, and this should be considered as one of the possible
      differential diagnoses. We were able to prevent the lethal consequences seen with
      coronary artery spasm by early diagnosis and management. 

PMID- 25070121
TI  - Impact of coronary plaque burden and composition on periprocedural myocardial
      infarction and coronary flow reserve after percutaneous coronary intervention.
AB  - Periprocedural myocardial infarction (PMI) is one of the major complications of
      percutaneous coronary intervention (PCI). We investigated the influence of
      coronary plaque burden and characteristics on PMI using intravascular ultrasound
      (IVUS) with radiofrequency-based tissue characterization technology (iMAP). The
      study population consisted of 33 consecutive patients with stable angina pectoris
      who underwent PCI. IVUS images were recorded before and after PCI for offline
      analysis, and coronary flow reserve (CFR) was measured after PCI. PMI was defined
      as a post-PCI cardiac troponin T elevation > 5 * 99(th) percentile of the upper
      reference limit (0.014 ng/mL). Plaque volume in patients with PMI (n = 12) was
      significantly greater than that in patients without PMI (n = 21) (240.4 +/- 106.0
      mm(3) versus 152.1 +/- 76.9 mm(3), P = 0.0096). The iMAP-IVUS analysis
      demonstrated that the fibrotic, lipidic, and necrotic tissue volume within
      culprit lesions were also greater in patients with PMI than in patients without
      PMI (129.4 +/- 52.2 mm(3) versus 94.6 +/- 40.8 mm(3), P = 0.041; 26.8 +/- 10.5
      mm(3) versus 15.8 +/- 11.5 mm(3), P = 0.011; and 81.3 +/- 48.4 mm(3) versus 40.2
      +/- 33.6 mm(3), P = 0.0071, respectively). Multivariate logistic analysis
      demonstrated that necrotic tissue volume was the only independent predictor of
      PMI. Multiple regression analysis demonstrated that the post-PCI CFR values
      signifi cantly correlated with percent plaque burden, and there were no
      correlations with the percent tissue burden of each plaque component. In
      conclusion, the iMAP-IVUS analyses demonstrate that necrotic tissue volume is a
      potent predictor of PMI. Microcirculatory disturbance after PCI is significantly
      influenced by percent plaque burden, regardless of plaque compositions. 

PMID- 25070122
TI  - Pericoronary pseudotumor caused by helicobacter cinaedi.
AB  - Cardiac tumors and tumor-like lesions are uncommon; most are true neoplasms. We
      here report a case of a pericoronary tumor-like lesion surrounding the right
      coronary artery in a 39-year-old man who presented with fever and chest pain.
      Although clarithromycin was administered for 1 week, his fever persisted.
      Helicobacter cinaedi (H. cinaedi) was isolated from blood cultures and found to
      be sensitive to ceftriaxone. A computed tomography scan showed a tumor-like
      lesion with no (18)F-fl uorodeoxyglucose uptake surrounding the right coronary
      artery. After administration of ceftriaxone, the tumor-like lesion diminished in
      size according to meticulous computed tomography examinations. We therefore
      concluded that it was caused by H. cinaedi infection. The patient has been
      followed up closely for 1 year and remains asymptomatic. 

PMID- 25070123
TI  - Thermal vasodilation using a portable infrared thermal blanket in decompensated
      heart failure.
AB  - Adjunctive and non-pharmacological therapies, such as heat, for the treatment of
      heart failure patients have been proposed. Positive results have been obtained in
      clinically stable patients, but no studies of the use of thermal therapy in
      patients with decompensated heart failure (DHF) have been reported. An open
      randomized clinical trial was designed in patients with DHF and controls. We
      studied 38 patients with a mean age of 56.9 years. A total of 86.8% were men, and
      71% had nonischemic myocardiopathy. All participants were using dobutamine, and
      the median brain natriuretic peptide (BNP) level was 1396 pg/mL. An infrared
      thermal blanket heated the patients, who were divided into 2 groups: group T
      (thermal therapy) and group C (control). Group T underwent vasodilation using the
      thermal blanket at 50 degrees C for 40 minutes in addition to drug treatment. The
      cardiac index increased by 24.1% (P = 0.009), and systemic vascular resistance
      decreased by 16.0% in group T (P < 0.024) after thermal therapy. Heat as a
      vasodilator increased the cardiac index and lowered systemic vascular resistance
      in DHF patients. These data suggest thermal therapy as a therapeutic approach for
      the adjuvant treatment of DHF patients. 

PMID- 25070124
TI  - New therapeutic approaches for treatment-resistant schizophrenia: a look to the
      future.
AB  - Schizophrenia for many patients is a lifelong mental disorder with significant
      consequences on most functional domains. One fifth to one third of patients with
      schizophrenia experience persistent psychotic symptoms despite adequate trials of
      antipsychotic treatment, and are considered to have treatment-resistant
      schizophrenia (TRS). Clozapine is the only medication to demonstrate efficacy for
      psychotic symptoms in such patients. However, clozapine is not effective in 40%
      70% of patients with TRS and it has significant limitations in terms of
      potentially life-threatening side effects and the associated monitoring.
      Accordingly, a number of pharmacological and non-pharmacological biological
      approaches for clozapine-resistant TRS have emerged. This article provides a
      brief updated critical review of recent therapeutic strategies for TRS,
      particularly for clozapine-resistant TRS, which include pharmacotherapy,
      electroconvulsive therapy, repetitive transcranial magnetic stimulation, and
      transcranial direct current stimulation. 

PMID- 25070125
TI  - Advances in Nod-like receptors (NLR) biology.
AB  - The innate immune system is composed of a wide repertoire of conserved pattern
      recognition receptors (PRRs) able to trigger inflammation and host defense
      mechanisms in response to endogenous or exogenous pathogenic insults. Among
      these, nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs)
      are intracellular sentinels of cytosolic sanctity capable of orchestrating innate
      immunity and inflammatory responses following the perception of noxious signals
      within the cell. In this review, we elaborate on recent advances in the signaling
      mechanisms of NLRs, operating within inflammasomes or through alternative
      inflammatory pathways, and discuss the spectrum of their effector functions in
      innate immunity. We describe the progressive characterization of each NLR with
      associated controversies and cutting edge discoveries. 

PMID- 25070126
TI  - Inequalities in healthcare access by type of visa in a context of restrictive
      health insurance policy: the case of Ukrainians in Czechia.

PMID- 25070127
TI  - Extraction of the fetal ECG in noninvasive recordings by signal decompositions.
AB  - No signal processing technique has been able to reliably deliver an undistorted
      fetal electrocardiographic (fECG) signal from electrodes placed on the maternal
      abdomen because of the low signal-to-noise ratio of the fECG recorded from the
      maternal body surface. As a result, this led to increased rates of Caesarean
      deliveries of healthy infants. In an attempt to solve the problem,
      Physionet/Computing in Cardiology announced the 2013 Challenge: noninvasive fetal
      ECG.We are suggesting a method for cancellation of the maternal ECG consisting
      of: maternal QRS detection, heart rate dependant P-QRS-T interval selection,
      location of the fiducial points inside this interval for best matching by cross
      correlation, superimposition of the intervals, calculation of the mean signal of
      the P-QRS-T interval, and sequential subtraction of the mean signal from the
      whole fECG recording. Three signal decomposition methods were further applied in
      order to enhance the fetal QRSs (fQRS): principal component analysis, root-mean
      square and Hotelling's T-squared. A combined lead of all decompositions was
      synthesized and fQRS detection was performed on it.The current research differs
      from the Challenge in that it uses three signal decomposition methods to enhance
      the fECG. The new results for 97 recordings of test set B are: 305.657 for Event
      4: Fetal heart rate (FHR) and 23.062 for Event 5: Fetal RR interval (FRR). 

PMID- 25070129
TI  - World Health Organization's Comprehensive Mental Health Action Plan 2013-2020.

PMID- 25070128
TI  - Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian
      adults: a cross-sectional study.
AB  - BACKGROUND: The epidemics of HIV and hypertension are converging in sub-Saharan
      Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living
      longer and gaining weight, putting them at greater risk for hypertension and
      kidney disease. The relationship between hypertension, kidney disease and long
      term ART among African adults, though, remains poorly defined. Therefore, we
      determined the prevalences of hypertension and kidney disease in HIV-infected
      adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We
      hypothesized that there would be a higher hypertension prevalence among HIV
      infected adults on ART, even after adjusting for age and adiposity. METHODS: In
      this cross-sectional study conducted between October 2012 and April 2013,
      consecutive adults (>18 years old) attending an HIV clinic in Tanzania were
      enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive,
      and 3) HIV-infected on ART for >2 years. The main study outcomes were
      hypertension and kidney disease (both defined by international guidelines). We
      compared hypertension prevalence between each HIV group versus the control group
      by Fisher's exact test. Logistic regression was used to determine if differences
      in hypertension prevalence were fully explained by confounding. RESULTS: Among
      HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community
      survey data). HIV-infected adults on ART had a higher prevalence of hypertension
      (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after
      adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model).
      HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151
      (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR= 0.35
      (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was <= 25%
      among hypertensive adults in all three groups. Kidney disease was common in all
      three groups (25.6% to 41.3%) and strongly associated with hypertension (P <0.001
      for trend); among hypertensive participants, 50/76 (65.8%) had microalbuminuria
      and 20/76 (26.3%) had an estimated glomerular filtration rate (eGFR) <60 versus
      33/184 (17.9%) and 16/184 (8.7%) participants with normal blood pressure.
      CONCLUSIONS: HIV-infected adults on ART >2 years had two-fold greater odds of
      hypertension than HIV-negative controls. HIV-infected adults with hypertension
      were rarely aware of their diagnosis but often have evidence of kidney disease.
      Intensive hypertension screening and education are needed in HIV-clinics in sub
      Saharan Africa. Further studies should determine if chronic, dysregulated
      inflammation may accelerate hypertension in this population.

PMID- 25070130
TI  - Prevalence and risk factors for skin diseases among antiretroviral-naive HIV
      infected pregnant women in Dar es Salaam, Tanzania.
AB  - BACKGROUND: Reduced cell-mediated immunity associated with pregnancy may cause a
      flaring or exacerbation of some skin conditions. Little is known about the
      magnitude of and risk factors for skin diseases among human immunodeficiency
      virus (HIV)-infected antiretroviral therapy-naive pregnant women. METHODS: Cross
      sectional study of 1078 HIV-infected antiretroviral therapy-naive pregnant women
      was conducted in Dar es Salaam, Tanzania. Skin diagnoses were mainly clinical.
      Log-binomial regression models were used to explore factors associated with the
      outcomes. RESULTS: About 84% of the women were in World Health Organization (WHO)
      HIV stage I. Median CD4(+) count was 405 * 10(6)  cells/l. The prevalence of any
      skin disease was 18%. Fungal infections (11%), genital ulcers (7%), and viral
      infections (5%) were the most common skin conditions. Skin infections were 2.64
      times more common in HIV stage III (95% CI 1.51-4.62) compared to stage I. Fungal
      infections were 1.77 times common among single, divorced, and widowed women than
      among married women (95% CI 1.16-2.69), 2.8 times common among women in HIV stage
      III (95% CI 1.18-6.64) compared to stage I. Genital ulcers were significantly
      more common among women whose source of income was their own compared with those
      who got full support from partners, and among WHO HIV stage III disease compared
      to stage I. CONCLUSION: The burden of skin diseases was relatively low. Advanced
      HIV stage was associated with a range of skin conditions. CD4(+) cell count was
      not related to skin infection prevalence.

PMID- 25070131
TI  - Epitope mapping of epidermal growth factor receptor (EGFR) monoclonal antibody
      and induction of growth-inhibitory polyclonal antibodies by vaccination with EGFR
      mimotope.
AB  - One of the proposed approaches in cancer therapy is to induce and direct the
      patient's own immune system against cancer cells. In this study, we determined
      the epitope mapping of the rat anti-human epidermal growth factor receptor (EGFR)
      monoclonal antibody ICR-62 using a phage display of random peptide library and
      identified a 12 amino acids peptide, which was recognized as a mimotope. The
      peptide was synthesized and conjugated to bovine serum albumin (BSA) as carrier
      protein (P-BSA). We have shown that ICR-62 can react specifically with P-BSA as
      well as native EGFR. Two rabbits were immunized either by BSA or P-BSA and the
      rabbits IgGs were purified and examined for binding to the antigens, mimotope and
      the EGFR protein purified from the EGFR overexpressing A431 cell line. We showed
      that the rabbit IgG generated against the mimotope is capable of inhibiting the
      growth of A431 cells by 15%, but does not have any effect on the growth of EGFR
      negative MDA-MB-453 cell line in vitro. Our results support the need for further
      investigations on the potential of vaccination with either mimotope of the EGFR
      or epitope displayed on the surface of phage particles for use in active
      immunotherapy of cancer.

PMID- 25070132
TI  - Professor John M. Fitzpatrick 1948-2014: a life in the fast lane.

PMID- 25070133
TI  - Routine data expose a need for change.

PMID- 25070134
TI  - Pushing the robot-assisted prostatectomy envelope--to the safety limits? Better
      outcomes.

PMID- 25070135
TI  - Upper tract urothelial carcinoma: do we really need to burn down the house?

PMID- 25070136
TI  - Unveiling the surgical risk associated with neoadjuvant chemotherapy in bladder
      cancer.

PMID- 25070137
TI  - The importance of knowing testosterone levels in patients with prostate cancer.

PMID- 25070138
TI  - A new model for the length of stay of hospital patients.
AB  - Hospital Length of Stay (LoS) is a valid proxy to estimate the consumption of
      hospital resources. Average LoS, however, albeit easy to quantify and calculate,
      can be misleading if the underlying distribution is not symmetric. Therefore the
      average does not reflect the nature of such underlying distribution and may mask
      different effects. This paper uses routinely collected data of an Italian
      hospital patients from different departments over a period of 5 years. This will
      be the basis for a running example illustrating the alternative models of
      patients length of stay. The models includes a new density model called
      Hypergamma. The paper concludes by summarizing these various modelling techniques
      and highlighting the use of a risk measure in bed planning. 

PMID- 25070139
TI  - Early drinking onset: a study of prevalence and determinants among 13-year-old
      adolescents in Norway.
AB  - Early drinking onset is associated with different psychosocial adjustment
      problems among adolescents. The aim of this study was to assess determinants
      associated with early drinking and to identify factors predicting early drinking
      onset among adolescents. The study included 1,550 eighth-graders with a mean age
      of 13.5 years from 41 schools. A total of 24% (boys 29%, girls 19%) had ever
      drunk alcohol, while 14% had drunk some alcohol in the last 30 days. Further,
      early drinking was associated with gender, religion, school performance, smoking
      and bullying in the bivariate tests. Predictors of early drinking onset were
      identified by generalized linear mixed models with two multivariable models
      created. The first model included social and environmental variables. Entering
      intentions, expectancies, attitudes and norms into the multivariable analysis
      resulted in a significant improvement of the model fit constituting 86% in the
      second model. The percentage correctly classified those (56%) who had been
      drinking in the second model which was two times higher compared to the first
      model. Gender, religion and smoking emerged as significant predictors of drinking
      in both models. 

PMID- 25070140
TI  - Melanoma manifesting as a verrucous lesion in the interdigital toe space.

PMID- 25070141
TI  - TCAB1: a potential target for diagnosis and therapy of head and neck carcinomas.
AB  - BACKGROUND: WRAP53, including alpha, beta and gamma isoforms, plays an important
      role not only in the stability of p53 mRNA, but also in the assembly and
      trafficking of the telomerase holoenzyme. It has been considered an oncogene and
      is thought to promote the survival of cancer cells. The aim of this study was to
      detect the role of TCAB1 (except WRAP53alpha) in the occurrence and development
      of head and neck carcinomas. METHODS: Immunohistochemistry was used to detect the
      TCAB1 expression in clinical specimen sections and performed western blotting to
      check the TCAB1 expression levels in cell lines. TCAB1 was depleted using shRNA
      lentivirus and the knockdown efficiency was assessed using q-PCR and Western
      blotting. We performed CCK-8 assays and flow cytometry to check the cell
      proliferation potential and used the trans-well assay to test the invasion
      ability in vitro. Xenografts were used to detect the tumor formation potential in
      vivo. Moreover, we performed cDNA microarray to investigate the candidate factors
      involved in this process. RESULTS: We observed a notable overexpression of TCAB1
      in head and neck carcinoma clinical specimens as well as in carcinoma cell lines.
      Knockdown of TCAB1 decreased the cellular proliferation potential and invasion
      ability in vitro. cDNA microarray analysis suggested the possible involvement of
      several pathways and factors associated with tumorigenesis and carcinoma
      development in the TCAB1-mediated regulation of cancers. Furthermore, the
      xenograft assay confirmed that the depletion of TCAB1 would inhibit tumor
      formation in nude mice. The immunohistochemistry results of the mice tumor tissue
      sections revealed that the cells in shTCAB1 xenografts showed decreased
      proliferation potential and increased apoptotic trend, meanwhile, the
      angiogenesis was inhibited in the smaller tumors form shTCAB1 cells. CONCLUSIONS:
      Our study demonstrated that depletion of TCAB1 decreased cellular proliferation
      and invasion potential both in vitro and in vivo. The data indicated that TCAB1
      might facilitate the occurrence and development of head and neck carcinomas. In
      future, TCAB1 might be useful as a prognostic biomarker or a potential target for
      the diagnosis and therapy of head and neck carcinomas.

PMID- 25070142
TI  - Anti-tumor necrosis factor drug survival in axial spondyloarthritis is
      independent of the classification criteria.
AB  - To compare the impact of meeting specific classification criteria [modified New
      York (mNY), European Spondyloarthropathy Study Group (ESSG), and Assessment of
      SpondyloArthritis international Society (ASAS) criteria] on anti-tumor necrosis
      factor (anti-TNF) drug retention, and to determine predictive factors of better
      drug survival. All patients fulfilling the ESSG criteria for axial
      spondyloarthritis (SpA) with available data on the axial ASAS and mNY criteria,
      and who had received at least one anti-TNF treatment were retrospectively
      retrieved in a single academic institution in Switzerland. Drug retention was
      computed using survival analysis (Kaplan-Meier), adjusted for potential
      confounders. Of the 137 patients classified as having axial SpA using the ESSG
      criteria, 112 also met the ASAS axial SpA criteria, and 77 fulfilled the mNY
      criteria. Drug retention rates at 12 and 24 months for the first biologic therapy
      were not significantly different between the diagnostic groups. Only the small
      ASAS non-classified axial SpA group (25 patients) showed a nonsignificant trend
      toward shorter drug survival. Elevated CRP level, but not the presence of bone
      marrow edema on magnetic resonance imaging (MRI) scans, was associated with
      significantly better drug retention (OR 7.9, ICR 4-14). In this cohort, anti-TNF
      drug survival was independent of the classification criteria. Elevated CRP level,
      but not positive MRI, was associated with better drug retention.

PMID- 25070143
TI  - Oxytocin nasal spray in fibromyalgic patients: additional information : reply to
      the comment to the editor entitled "future directions for the investigation of
      intranasal oxytocin and pain".

PMID- 25070144
TI  - Probing the aggregation behavior of 4-aminophthalimide and 4-(N,N-dimethyl) amino
      N-methylphthalimide: a combined photophysical, crystallographic, microscopic and
      theoretical (DFT) study.
AB  - Two fluorescent molecules, 4-aminophthalimide (AP) and 4-(N,N-dimethyl)amino-N
      methylphthalimide (DMP) have been used as the building blocks to fabricate
      fluorescent organic nano particles. DMP, the analogue of AP, has been synthesized
      by substituting all the amine hydrogens of AP with methyl groups to get an idea
      about the effect of intermolecular hydrogen bonding interactions (N-H...) on the
      aggregation behavior of these molecules. All the systems have been characterized
      by field emission scanning electron microscopy (FESEM). Photophysical behavior of
      these well characterized systems has been investigated in molecular as well as
      aggregated forms. Interestingly, while the AP-aggregates exhibit a blue-shifted
      absorption band (as compared to AP in its molecular form), DMP-aggregates exhibit
      a red-shifted absorption band (as compared to DMP in its molecular form). These
      absorption data indicate the formation of H and J aggregates for AP and DMP,
      respectively. The intermolecular interactions that are responsible for the
      molecular self assembly of AP and DMP are studied by using X-ray crystallography.
      X-ray analysis demonstrates the presence of strong intermolecular hydrogen
      bonding interactions in AP, but only weak interactions (C-H...O, C-H...pi) in the
      case of DMP. X-ray analysis also demonstrates that varying the nature of
      intermolecular interactions leads to different modes of aggregation. Theoretical
      studies (DFT and TD-DFT) have been carried out to investigate how different modes
      of aggregation lead to changes in the optical (UV-VIS spectra) properties of
      these systems.

PMID- 25070145
TI  - Subcutaneous nodule on the scrotum.

PMID- 25070146
TI  - Recent advances in heterobimetallic palladium(II)/copper(II) catalyzed domino
      difunctionalization of carbon-carbon multiple bonds.
AB  - The double functionalization of carbon-carbon multiple bonds in one-pot processes
      has emerged in recent years as a fruitful tool for the rapid synthesis of complex
      molecular scaffolds. This review covers the advances in domino reactions promoted
      by the couple palladium(ii)/copper(ii), which was proven to be an excellent
      catalytic system for the functionalization of substrates. 

PMID- 25070147
TI  - Slight elevation of high-sensitivity C-reactive protein to predict recurrence and
      survival in patients with early stage hepatitis C-related hepatocellular
      carcinoma.
AB  - AIM: Hepatocellular carcinoma (HCC) is associated with chronic inflammation
      derived from various origins. We investigated whether high-sensitivity C-reactive
      protein (hsCRP) could predict recurrence and survival after curative treatment
      for early stage hepatitis C virus-related HCC (C-HCC). METHODS: We enrolled 387
      patients with three or fewer C-HCC nodules, none of which exceeded 3 cm, and of
      Child-Pugh class A or B who underwent radiofrequency ablation. We divided the
      patients into high and low hsCRP groups based on the optimal cut-off value for
      recurrence using a split-sample method and maximally selected rank statistics.
      Differences in recurrence and survival rates were evaluated by the Kaplan-Meier
      method and the log-rank test. Hazard ratios of hsCRP were adjusted with
      confounding factors using a multiple Cox regression model. We also assessed the
      correlations between hsCRP levels and clinical parameters. RESULTS: The optimal
      hsCRP cut-off value was 0.08 mg/dL. The cumulative recurrence rates after 5 years
      in the high and low hsCRP groups were 90.0% and 82.2%, respectively (P = 0.028),
      and the corresponding survival rates were 50.9% and 71.8%, respectively (P <
      0.001). Higher hsCRP was an independent predictor for recurrence (adjusted hazard
      ratio [aHR], 1.32; 95% confidence interval [CI], 1.03-1.67; P = 0.026) and
      survival (aHR, 1.59; 95% CI, 1.14-2.22; P = 0.007). hsCRP was correlated with
      central obesity as well as tumor burden and liver dysfunction. CONCLUSION: Slight
      elevation of the hsCRP level, even within the normal range, can predict
      recurrence and survival after curative treatment among patients with early stage
      C-HCC.

PMID- 25070149
TI  - Pillar[5]arene-based supramolecular organic frameworks for highly selective CO2
      capture at ambient conditions.
AB  - Low-density, solid-state, porous supramolecular organic frameworks are
      constructed using pillarenes. The frameworks have a honeycomb-like structure,
      permanent porosity, high thermal stability, and selective and reversible sorption
      properties toward CO2. The exceptionally selective CO2-sorption properties
      (375/1, 339/1) of one framework over N2 and CH4 indicate potential applications
      in CO2-capture for post-combustion power plants and natural gas sweetening.

PMID- 25070148
TI  - Long-term safety and efficacy of single-tablet combinations of solifenacin and
      tamsulosin oral controlled absorption system in men with storage and voiding
      lower urinary tract symptoms: results from the NEPTUNE Study and NEPTUNE II open
      label extension.
AB  - BACKGROUND: Short-term trials have demonstrated the efficacy and safety of
      combination therapy using antimuscarinics and alpha-blockers in men with lower
      urinary tract symptoms (LUTS). The Study of Solifenacin Succinate and Tamsulosin
      Hydrochloride OCAS (oral controlled absorption system) in Males with Lower
      Urinary Tract Symptoms (NEPTUNE) II is the first long-term study using
      solifenacin (Soli) and the oral controlled absorption system formulation of
      tamsulosin (TOCAS). OBJECTIVE: To evaluate long-term (up to 52 wk) safety and
      efficacy of flexible dosing of two fixed-dose combinations (FDC) of Soli plus
      TOCAS in men with moderate to severe storage symptoms and voiding symptoms.
      DESIGN, SETTING, AND PARTICIPANTS: Patients with both storage and voiding LUTS,
      maximum urinary flow rate of 4.0-12.0 ml/s, prostate size <75 ml, and postvoid
      residuals <= 150 ml, who completed the 12-wk, double-blind NEPTUNE study could
      continue in the 40-wk, open-label NEPTUNE II study. INTERVENTION: FDC of Soli 6
      mg plus TOCAS 0.4 mg, or Soli 9 mg plus TOCAS 0.4mg; patients could switch
      between doses in NEPTUNE II. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Safety and efficacy data from NEPTUNE and NEPTUNE II were combined to cover a 52
      wk period. Primary efficacy end points were total International Prostate Symptom
      Score (IPSS) and total urgency and frequency score (TUFS); secondary end points
      included IPSS storage and voiding subscores, micturition diary variables, and
      quality of life parameters. RESULTS: In all, 1066 men completed NEPTUNE and
      received one dose or more of study medication in NEPTUNE II. Treatment-emergent
      adverse events were reported in 499 (46.8%) patients who participated in NEPTUNE
      II; most were mild or moderate. Urinary retention occurred in 13 of 1208 (1.1%)
      patients receiving one or more FDCs in NEPTUNE and/or NEPTUNE II; 8 (0.7%)
      required catheterisation (acute urinary retention [AUR]). Reductions in total
      IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment,
      with mean reductions of 9.0 (standard deviation [SD]: 5.7) and 10.1 (SD: 9.2),
      respectively, from baseline to end of treatment. Clinically relevant improvements
      were also observed for secondary efficacy end points. CONCLUSIONS: Long-term
      treatment with FDC Soli plus TOCAS was well tolerated and efficacious in men with
      storage and voiding LUTS, with a low incidence of AUR. PATIENT SUMMARY: Treatment
      with solifenacin plus tamsulosin in a fixed-dose combination tablet was well
      tolerated by men with lower urinary tract symptoms. Improvements in symptoms were
      achieved after 4 wk of treatment, with further improvements at week 16 maintained
      for up to 52 wk throughout the study.

PMID- 25070151
TI  - Immunofluorescence mapping in inherited epidermolysis bullosa: a study of 86
      cases from India.
AB  - BACKGROUND: Epidermolysis bullosa (EB) poses diagnostic challenges in infancy. In
      India, the diagnosis is largely clinical. There were no facilities to perform
      immunofluorescence mapping (IFM) until recently, and electron microscopy, which
      requires expertise to interpret, is limited to a few research laboratories.
      OBJECTIVES: To describe the patterns of IFM staining in the various forms of EB
      in Indian patients and to correlate these findings with clinical diagnosis.
      METHODS: We conducted a cross-sectional study of IFM findings in EB. Antibodies
      against type IV collagen, cytokeratin 14, laminin 332 and type VII collagen were
      used. Clinical correlation was performed in all cases, and concordance
      discordance rates were calculated. RESULTS: Eighty-six patients with a diagnosis
      of EB were included in the study. There were 29 with EB simplex (EBS), 18 with
      junctional EB (JEB) and 15 with dystrophic EB (DEB). The remaining 24 cases
      included rare variants, cases with overlapping clinical features and cases where
      the type of EB was not known. On IFM diagnosis, there were 32 cases of EBS, 15
      JEB, 17 DEB and two Kindler syndrome. Two cases were not EB and 18 were
      inconclusive. IFM could establish the type in 12 of 15 cases (80%) that had
      overlapping clinical features. Most of these cases were under 1 year of age.
      Overall the concordance was 57% and was seen best in cases of EBS. CONCLUSIONS:
      This is the first large study of IFM of the subtypes of EB in Indian patients.
      The study provides a framework for better understanding of EB in Indian patients
      and for better diagnosis and management, particularly in infancy.

PMID- 25070150
TI  - A SNP in intron 8 of CD46 causes a novel transcript associated with mastitis in
      Holsteins.
AB  - BACKGROUND: The membrane protein CD46, a ubiquitous cell surface pathogen
      receptor, can bind Streptococcus to trigger cell autophagy, which is a critical
      step in the control of infection. RESULTS: In this study, we found a new splice
      variant designated CD46 transcript variant (CD46-TV). The splice variant is
      characterized by the retention of a 48 bp sequence from intron 8 of the bovine
      CD46 gene, which encodes a putative protein enlarged by 16 amino acids. CD46-TV
      mRNA was found to be over expressed in mastitis-infected mammary gland tissues
      relative to healthy tissues. A single nucleotide polymorphism (c. 1033 + 2184 C >
      T) in the exonic splicing enhancer (ESE) motif region was shown to result in the
      CD46-TV aberrant splice variant through constructing alternative alleles using
      the pSPL3 exon capturing vector and transfecting these into 293 T cells. Allelic
      frequency in 56,682 individuals belonging to 112 Bos taurus, Bos indicus, Bos
      javanicus, Bos grunniens and Bos mutus, etc. suggests that the C allele (80.09%)
      is the ancestral allele. Association analysis found that the mean genomic
      estimated breeding values (gEBV) for milk somatic cell score and the occurrence
      of clinical mastitis, as well as the milk somatic cell score of Chinese Holsteins
      with the CT genotype was lower than those of individuals with either the CC or TT
      genotypes. The mean gEBV for udder health synthesis for the TT genotype was
      greater than those for the CC or CT genotypes. CONCLUSIONS: Our findings suggest
      that the CD46 gene likely plays a critical role in the risk of mastitis caused by
      Streptococcus in dairy cows via an alternative splicing mechanism caused by a
      functional mutation in intron 8. Our data also underline the importance of
      variation within ESEs in regulating transcript processing.

PMID- 25070152
TI  - Concise review: tissue-specific microvascular endothelial cells derived from
      human pluripotent stem cells.
AB  - Accumulating evidence suggests that endothelial cells (ECs) display significant
      heterogeneity across tissue types, playing an important role in tissue
      regeneration and homeostasis. Recent work demonstrating the derivation of tissue
      specific microvascular endothelial cells (TS-MVECs) from human pluripotent stem
      cells (hPSCs) has ignited the potential to generate tissue-specific models which
      may be applied to regenerative medicine and in vitro modeling applications. Here,
      we review techniques by which hPSC-derived TS-MVECs have been made to date and
      discuss how current hPSC-EC differentiation protocols may be directed toward
      tissue-specific fates. We begin by discussing the nature of EC tissue specificity
      in vivo and review general hPSC-EC differentiation protocols generated over the
      last decade. Finally, we describe how specificity can be integrated into hPSC-EC
      protocols to generate hPSC-derived TS-MVECs in vitro, including EC and
      parenchymal cell coculture, directed differentiation, and direct reprogramming
      strategies.

PMID- 25070153
TI  - Improvement of myocardial fatty acid metabolism by oral nicorandil in
      hemodialysis patients without coronary artery disease.
AB  - BACKGROUND: We investigated the potential of oral nicorandil to improve
      myocardial fatty acid metabolism assessed by single-photon emission computed
      tomography (SPECT) using (123)I-beta-methyliodophenyl pentadecanoic acid (BMIPP)
      in hemodialysis patients without obstructive coronary artery disease (CAD).
      METHODS: This study was based on a cohort study of 155 hemodialysis patients with
      angiographic absence of obstructive CAD, with analysis performed in 100
      propensity-matched patients (54 men and 46 women, 64 +/- 10 years); 50 with oral
      administration of nicorandil (15 mg/d, nicorandil group) and 50 without
      (control). BMIPP SPECT was performed every year after angiography. Uptake on
      SPECT was graded in 17 segments on a five-point scale (0 normal, 4 absent) and
      assessed as BMIPP summed scores (SS). RESULTS: Over a mean follow-up period of
      5.3 +/- 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched
      patients. Myocardial uptake of BMIPP in SPECT improved in the nicorandil group
      compared with the control group from 2 years of administration. In Kaplan-Meier
      survival analyses, free survival rate from cardiac death was higher in patients
      with a BMIPP SS improvement rate of >=20% compared to those with >=0% <20% or
      with <0% BMIPP SS improvement rate. At multiple logistic analysis, a >=20% BMIPP
      SS improvement rate was positively associated with serum albumin concentration
      and oral nicorandil. CONCLUSIONS: Long-term oral nicorandil may inhibit cardiac
      death by improving myocardial fatty acid metabolism in hemodialysis patients
      without obstructive CAD.

PMID- 25070154
TI  - "My body breaks. I take solution." Inhalant use in Delhi as pleasure seeking at a
      cost.
AB  - BACKGROUND: Inhalant use has existed in India since the 1970s and has increased
      significantly over the last decades, especially among street-oriented young
      people. The latter constitute a heterogeneous category: children from street
      families, children 'of' the street, rag pickers, and part-time street children.
      There are also inhalant-using schoolchildren and young people in slums. METHODS:
      Fieldwork was conducted for 1 year. Team ethnography, multi-sited and comparative
      research, flexibility of methods and writing field notes were explicit parts of
      the research design. Most research was undertaken with six groups in four areas
      of Delhi, exemplifying six generic categories of inhalant-using street-oriented
      young people. RESULTS: Inhalants in India are branded: Eraz-Ex diluter and
      whitener, manufactured by Kores, are used throughout Delhi; Omni glue in one
      specific area. There is a general lack of awareness and societal indifference
      towards inhalant use, with the exception of the inhalant users themselves, who
      possess practical knowledge. They conceive of inhalants as nasha, encapsulating
      the materiality of the substances and the experiential aspects of intoxication
      and addiction. Fragments of group interviews narrate the sensory appeal of
      inhalants, and an ethnographic vignette the dynamics of a sniffing session. These
      inhalant-using street children seek intoxication in a pursuit of pleasure,
      despite the harm that befalls them as a result. Some find nasha beautiful,
      notwithstanding the stigmatization, violence and bodily deterioration; others
      experience it as an overpowering force. CONCLUSION: A source of attraction and
      pleasure, inhalants ravage street children's lives. In this mysterious space of
      lived experience, their self-organization evolves. Distinguishing between hedonic
      and side effects, addiction helps to understand inhalant use as at once
      neurobiological, cultural, and involving agency. The implications are that India
      needs to develop a policy of treatment and employment to deal with the addiction.

PMID- 25070155
TI  - Rationale for "cultural" native patient navigators in Indian country.

PMID- 25070156
TI  - Blood loses it when nerves go bad.
AB  - Myeloproliferative neoplasms are diseases that arise in the stem cells of the
      blood. In a recent paper published in Nature, Arranz et al. demonstrated that
      abrogation of sympathetic nerve fibers reduced bone marrow Nestin mesenchymal
      cells, which in turn led to an expansion of hematopoietic stem cells and
      progression of myeloproliferative neoplasms. 

PMID- 25070157
TI  - Clinical impact of the Warburg effect in gastrointestinal cancer (review).
AB  - Cancer cells exhibit altered glucose metabolism, termed the Warburg effect, which
      is described by the increased uptake of glucose and the conversion of glucose to
      lactate in cancer cells under adequate oxygen tension. Recent genetic and
      metabolic analyses have provided insights into the molecular mechanisms of genes
      that are involved in the Warburg effect and tumorigenesis. The aim of this review
      was to discuss significant molecular insights into clinical impacts of the
      Warburg effect such as oncogenic alterations and overexpression of
      transcriptional factors (c-Myc and hypoxia-inducible factor), metabolite
      transporters (glucose transporters) and glycolytic enzymes (hexokinases 2,
      pyruvate kinase M2, pyruvate dehydrogenase kinase, isozyme 1, lactate
      dehydrogenase A). Overexpression of transcriptional factors, metabolite
      transporters and glycolytic enzymes was associated with poor prognosis and may be
      associated with chemoradiotherapy resistance in multiple gastrointestinal cancer
      cell types. Novel small molecules targeting these enzymes or transporters exert
      anti-proliferative effects. Glycolytic enzymes and metabolite transporters may be
      significant biomarkers for predicting cancer prognosis and may be therapeutic
      targets in gastrointestinal cancer. 

PMID- 25070158
TI  - Safety and efficacy of coformulated efavirenz/emtricitabine/tenofovir single
      tablet regimen in treatment-naive patients infected with HIV-1.
AB  - Due to the differences between bioavailability of efavirenz (EFV) and tenofovir
      (TDF), the single-tablet regimen of EFV/emtricitabine (FTC)/TDF is not approved
      as initial antiretroviral therapy (ART) in Europe by the European Medical Agency.
      To compare clinical, immunological, and virological outcomes between co
      formulated TDF/FTC+EFV and the co-formulated EFV/FTC/TDF single-tablet regimen in
      patients infected with HIV-1 naive to ART, the data of patients (n = 231) who
      initiated either TDF/FTC+EFV (n = 155) or EFV/FTC/TDF (n = 76) between January 1,
      2007 and June 1, 2010 were analyzed. Changes from baseline to week 48
      (TDF/FTC+EFV vs. EFV/FTC/TDF) in HIV plasma load (- 3.25 log vs. -3.32 log) and
      CD4+ T cell count (+180 vs. +138 cells/mm3) were similar in the two groups.
      Treatment discontinuation was recorded in 50 (22%) patients (40 on TDF/FTC+EFV
      and 10 on EFV/FTC/TDF, P = 0.03) but time to discontinuation did not differ
      between the two groups. Only patients on TDF/FTC+EFV discontinued treatment
      because of neurological symptoms. Virological failure occurred in 11 (4.7%)
      patients (seven on TDF/FTC+EFV and four on EFV/FTC/TDF, P = 0.75) with new
      resistance-associated mutations in five among the six with successful resistance
      genotype tests. Only baseline resistance-associated mutations was a risk factor
      for virological failure (P = 0.0146). These data show comparable outcomes between
      TDF/FTC+EFV or EFV/FTC/TDF used in patients infected with HIV-1 and not treated
      previously, consistent with a low rate of virological failure in the absence of
      pretreatment resistance. This would suggest that the European Medical Agency
      should approve co-formulated EFV/FTC/TDF single-tablet regimen for patients naive
      to ART.

PMID- 25070159
TI  - Optimization of storage condition for maintaining long-term viability of
      nematophagous fungus Esteya vermicola as biocontrol agent against pinewood
      nematode.
AB  - The fungus, Esteya vermicola has been proposed as biocontrol agent against pine
      wilting disease caused by Bursaphelenchus xylophilus. In this study, we reported
      the effects of temperature and different additives on the viability and
      biocontrol efficacy of E. vermicola formulated by alginate-clay. The viability of
      the E. vermicola formulation was determined for six consecutive months at
      temperature ranged from -70 to 25  degrees C. The fresh conidia without any
      treatment were used as control. Under the optimal storage conditions with E.
      vermicola alginate-clay formulation, the results suggested that E. vermicola
      alginate-clay formulation with a long shelf life could be a non-vacuum-packed
      formulation that contains 2 % sodium alginate and 5 % clay at 4  degrees C. Three
      conidial formulations prepared with additives of 15 % glycerol, 0.5 % yeast
      extract and 0.5 % herbal extraction, respectively significantly improved the
      shelf life. In addition, these tested formulations retained the same biocontrol
      efficacy as the fresh conidial against pinewood nematode. This study provided a
      tractable and low-cost method to preserve the shelf life of E. vermicola.

PMID- 25070160
TI  - Effects of a hydrogen sulfide donor on spontaneous contractile activity of rat
      stomach and jejunum.
AB  - We studied the effect of sodium hydrosulfite (NaHS), a donor of hydrogen sulfide
      (H2S), on spontaneous contractive activity of isolated preparations of rat
      stomach and jejunum under isometric conditions. NaHS in concentrations of 10-200
      MUM reduced the amplitude, tonic tension, and frequency of contractions of the
      preparations. Blockade of K(+) channels with a non-specific antagonist
      tetraethylammonium (10 mM) increased contraction amplitude in the stomach strip
      and jejunum segment. The effects of NaHS on all parameters of contractile
      activity of the stomach and jejunum were fully preserved against the background
      of tetraethylammonium application. These data suggest that H2S in physiologically
      relevant concentrations inhibited spontaneous contractile activity of smooth
      muscle cells in rat stomach and jejunum by reducing the amplitude and frequency
      of contractions and decreased tonic tension without affecting the function of
      voltage- and calcium-dependent K(+) channels. 

PMID- 25070161
TI  - Ratio of antibodies to neurotransmitters in the serum of students, occasional
      drug users.
AB  - The survey included volunteer students of secondary and higher educational
      institutions. Two groups have been formed based on the results of clinical and
      laboratory studies. Group 1 comprised students occasionally using cannabinoids
      and amphetamines (risk group for psychoactive substances addiction) and group 2
      included students who do not use drugs. The serum level of autoantibodies to
      norepinephrine, dopamine, and serotonin was reduced in the risk group. 

PMID- 25070162
TI  - Effect of 5-HT(2A) receptor antagonists on blood flow in the carotid vessels upon
      elevation of serotonin level.
AB  - We studied the ability of predominantly 5-HT2A receptor antagonists to prevent a
      serotonin-induced change of blood flow in the carotid vessels of rats with
      experimental serotonin-induced spasm. Ritanserin, ketanserin, and 5-HT2A receptor
      antagonist RU-476 reduced the effect of serotonin on the blood fl ow velocity in
      the internal carotid artery by 2.3, 1.7, and 2.6 times, respectively. 

PMID- 25070163
TI  - Modulation of macrophages and response of CD117(+) cells of different
      localization after liver damage in mice.
AB  - We studied the effects of stimulation of mononuclear phagocyte system on the
      state of CD117(+) hepatocytes of growth zone and CD117(+) hemopoietic stem cells
      after liver damage. Increased number of CD117(+) hepatocytes and enhanced
      expression of given antigen was revealed. CD117(+) hemopoietic stem cells respond
      to the impact by migration to the regenerating organ. 

PMID- 25070164
TI  - Expression of circadian rhythm genes CLOCK, BMAL1, and PER1 in buccal epithelial
      cells of patients with essential arterial hypertension in dependence on
      polymorphic variants of CLOCK and BMAL1 genes.
AB  - The transcript levels of circadian rhythm genes CLOCK, BMAL1, and PER1 in buccal
      epithelial cells of the patients with essential arterial hypertension was
      analyzed in relation to polymorphic variants of CLOCK and BMAL1 genes. These
      levels were assessed with realtime PCR method at daily hours 9, 13, and 17. The
      significant differences were revealed in transcript levels of the examined genes
      in patients with various genotypes at the polymorphic markers 3111TC and 257TG
      regulatory regions of CLOCK gene. The study detected no significant differences
      among the carriers of various genotypes at polymorphic markers 862TC and 2121GA
      of CLOCK gene and 56445TC of BMAL1 gene.

PMID- 25070165
TI  - Purification of high-molecular-weight subfraction from porcine skin inhibiting
      proliferation of A431 human carcinoma epidermoid cells.
AB  - Subfraction with a molecular weight >250 kDa isolated from porcine skin and
      inhibiting the proliferation of A431 human carcinoma epidermoid cells was
      purified by DEAE 32 anion exchange chromatography with NaCl concentration step
      gradient. The effects of the initial subfraction and fractions obtained by
      separation in DEAE 32 on the proliferation of A431 human carcinoma epidermoid
      cells were studied in vitro in two tests (MTT and fluorescent test). The more
      sensitive fluorescent test showed the highest inhibitory activity of fraction No.
      2 released from the column at 0.15 M NaCl. One major protein component and a
      series of minor protein components were detected in this fraction by vertical
      PAAG-SDS electrophoresis.

PMID- 25070166
TI  - Ultrafast Ramsey interferometry to implement cold atomic qubit gates.
AB  - Quantum computing is based on unitary operations in a two-level quantum system, a
      qubit, as the fundamental building block, and the ability to perform qubit
      operations in an amount of time that is considerably shorter than the coherence
      time is an essential requirement for quantum computation. Here, we present an
      experimental demonstration of arbitrary single-qubit SU(2) quantum gate
      operations achieved at a terahertz clock speed. Implemented by coherent control
      methods of tailored ultrafast laser interaction with cold rubidium atomic qubits,
      Bloch vector manipulation about all three rotational axes was successfully
      demonstrated. The dynamic evolution of the qubits was successfully measured by
      devised femtosecond Ramsey interferometry. We anticipate this demonstration to be
      a starting point to process quantum algorithm in a simplified manner by a
      programmed sequence of femtosecond laser pulses. 

PMID- 25070167
TI  - Ethics and etiquette in neonatal intensive care.
AB  - When parents voice their dissatisfaction with the neonatal intensive care unit
      (NICU), it is often not because they think their baby has not received good
      medical care. Instead, it is often because their needs have not been addressed.
      Policy statements and pedagogy alike urge professionals to be empathetic,
      compassionate, honest, and caring. However, these theoretical concepts are
      generally endorsed without practical suggestions on how to achieve these goals.
      Negative encounters for parents are generally not about the caregivers' technical
      expertise or knowledge and often reflect a failure in a different domain. Simple
      rules of etiquette are not always applied in a busy NICU or in the hospital at
      large. The investigators of the POST (Parents from the Other Side of Treatment)
      group are health care professionals who regularly communicate with parents of
      sick children and who were also "NICU parents." We have developed an etiquette
      based systematic approach to communication with families in the NICU. These
      specific and practical recommendations may help parents feel well treated and
      respected as they go through a challenging NICU stay. 

PMID- 25070168
TI  - Differential response of nonadapted ammonia-oxidising archaea and bacteria to
      drying-rewetting stress.
AB  - Climate change is expected to increase the frequency of severe drought events
      followed by heavy rainfall, which will influence growth and activity of soil
      microorganisms, through osmotic stress and changes in nutrient concentration.
      There is evidence of rapid recovery of processes and adaptation of communities in
      soils regularly experiencing drying/rewetting and lower resistance and resilience
      in nonadapted soils. A microcosm-based study of ammonia-oxidising archaea (AOA)
      and bacteria (AOB), employing a grassland soil that rarely experiences drought,
      was used to test this hypothesis and also whether AOB were more resistant and
      resilient, through greater tolerance of high ammonia concentrations produced
      during drought and rewetting. Treated soils were dried, incubated for 3 weeks,
      rewetted, incubated for a further 3 weeks and compared to untreated soils,
      maintained at a constant moisture content. Nitrate accumulation and AOA and AOB
      abundance (abundance of respective amoA genes) and community composition (DGGE
      analysis of AOA amoA and AOB 16S rRNA genes) were poorly adapted to drying
      rewetting. AOA abundance and community composition were less resistant than AOB
      during drought and less resilient after rewetting, at times when ammonium
      concentration was higher. Data provide evidence for poor adaptation of microbial
      communities and processes to drying-rewetting in soils with no history of drought
      and indicate niche differentiation of AOA and AOB associated with high ammonia
      concentration.

PMID- 25070169
TI  - Radiotherapy treatment planning with contrast-enhanced computed tomography:
      feasibility of dual-energy virtual unenhanced imaging for improved dose
      calculations.
AB  - BACKGROUND: In radiotherapy treatment planning, intravenous administration of an
      iodine-based contrast agent during computed tomography (CT) improves the accuracy
      of delineating target volumes. However, increased tissue attenuation resulting
      from the high atomic number of iodine may result in erroneous dose calculations
      because the contrast agent is absent during the actual procedure. The purpose of
      this proof-of-concept study was to present a novel framework to improve the
      accuracy of dose calculations using dual-energy virtual unenhanced CT in the
      presence of an iodine-based contrast agent. METHODS: Simple phantom experiments
      were designed to assess the feasibility of the proposed concept. By utilizing a
      "second-generation" dual-source CT scanner equipped with a tin filter for
      improved spectral separation, four CT datasets were obtained using both a water
      phantom and an iodine phantom: "true unenhanced" images with attenuation values
      of 2 +/- 11 Hounsfield Units (HU), "enhanced" images with attenuation values of
      274 +/- 23 HU, and two series of "virtual unenhanced" images synthesized from
      dual-energy scans of the iodine phantom, each with a different combination of
      tube voltages. Two series of virtual unenhanced images demonstrated attenuation
      values of 12 +/- 29 HU (with 80 kVp/140 kVp) and 34 +/- 10 HU (with 100 kVp/140
      kVp) after removing the iodine component from the contrast-enhanced images. Dose
      distributions of the single photon beams calculated from the enhanced images and
      two series of virtual unenhanced images were compared to those from true
      unenhanced images as a reference. RESULTS: The dose distributions obtained from
      both series of virtual unenhanced images were almost equivalent to that from the
      true unenhanced images, whereas the dose distribution obtained from the enhanced
      images indicated increased beam attenuation caused by the high attenuation
      characteristics of iodine. Compared to the reference dose distribution from the
      true unenhanced images, the dose distribution pass rates from both series of
      virtual unenhanced images were greater than 90%, while those from the enhanced
      images were less than approximately 50-60%. CONCLUSIONS: Dual-energy virtual
      unenhanced CT improves the accuracy of dose distributions in radiotherapy
      treatment planning by removing the iodine component from contrast-enhanced
      images.

PMID- 25070170
TI  - Comparison of food antioxidants and iron chelators in two cellular free radical
      assays: strong protection by luteolin.
AB  - Liver (HepG2) cells were incubated with 21 edible flavonoids, carotenoids,
      polyunsaturated fatty acid (PUFA) chromones, and metal chelators for 1 h, washed
      in PBS, and challenged in the cellular antioxidant activity (CAA) and the
      cellular lipid peroxidation antioxidant activity (CLPAA) assays. These microplate
      format assays assess the compounds' ability to protect against cytosolic peroxyl
      radicals (CAA) and induced membrane lipid peroxidation (CLPAA), respectively.
      Incubation encompassing a broad compound concentration range determined half
      maximal inhibitory concentrations (IC(50)) by using sigmoidal curve fits.
      Overall, considering both assays, luteolin offered the greatest protection. The
      carotenoid astaxanthin offered only modest protection, whereas beta-carotene was
      ineffective. Subtle structural differences between flavonoids were found to have
      amplified effects on protective abilities, and mechanisms of flavonoid
      antioxidant action are discussed. Membrane-permeable iron chelators (deferasirox
      and SIH) offered strong protective effects in CLPAA, but not in CAA, suggesting
      that CLPAA is dependent on membrane-associated free iron ions.

PMID- 25070171
TI  - Between physics and metaphysics: structure as a boundary concept.
AB  - The notion of structure is found to be used in a great number of theories,
      scientific research programs and world views. However, its uses and definitions
      are as diverse as the objects of the scientific disciplines where it can be
      found. Without trying to recreate the structuralist aspiration from the mid XX
      century, which believed to have found in this notion a common transdisciplinary
      language, I discuss a specific aspect of this concept that could be considered a
      constant in different perspectives. This aspect refers to the location of the
      notions of structure as boundaries in the different scientific theories. With
      this, I try to argue that the definition or presentation of a structure
      configures in itself the frontier for scientific knowledge, defining at the same
      time implied ontological assumptions. In order to discuss this hypothesis, and
      taking into consideration the double origin of contemporary notions of structure 
      the mathematical and linguistic line-, I revise several theoretical perspectives
      which made explicit the relation between structures and knowledge, and their
      relation with the real: the arguments on physical knowledge by Eddington,
      structural anthropology, structural linguistics, Lacanian psychoanalysis and
      Piaget's genetic psychology. 

PMID- 25070173
TI  - Is it really worth it? Reply to: Selective use of bioabsorbable Gore BIO-A plug
      and patch for groin hernia repair. Negro P, Campanelli G, Ipponi PL, Gossetti F,
      Dassatti MR, Manto O, D'Amore L. Hernia. 2013, 17(6):795-6.

PMID- 25070172
TI  - Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer
      subtypes.
AB  - BACKGROUND: Gross cystic disease fluid protein 15 (GCDFP-15), which is regulated
      by the androgen receptor (AR), is a diagnostic marker for mammary differentiation
      in histopathology. We determined the expression of GCDFP-15 in breast cancer
      subtypes, its potential prognostic and predictive value, as well as its
      relationship to AR expression. METHODS: 602 pre-therapeutic breast cancer core
      biopsies from the phase III randomized neoadjuvant GeparTrio trial (NCT00544765)
      were investigated for GCDFP-15 expression by immunohistochemistry. Expression
      data were correlated with disease-free (DFS) and overall survival (OS) time as
      well as pathological complete response (pCR) to neoadjuvant chemotherapy.
      RESULTS: 239 tumors (39.7%) were GCDFP-15 positive. GCDFP-15 expression was
      positively linked to hormone receptor (HR) and HER2 positive tumor type, while
      most triple negative carcinomas were negative (p < 0.0001). GCDFP-15 was also
      strongly correlated to AR expression (p 0.001), and to the so-called molecular
      apocrine subtype (HR-/AR+, p < 0.0001). Higher rates of GCDFP-15 positivity were
      seen in tumors of lower grade (<0.0001) and negative nodal status (p = 0.008).
      GCDFP-15 positive tumors tended to have a more favourable prognosis than GCDFP-15
      negative tumors (DFS (p = 0.052) and OS (p = 0.044)), which was not independent
      from other factors in multivariate analysis. GCDFP-15 expression was not linked
      to pCR. Histological apocrine differentiation was frequent in molecular apocrine
      carcinomas (60.7%), and was associated with GCDFP-15 within this group (p =
      0.039). CONCLUSIONS: GCDFP-15 expression is higher in tumors with favorable
      prognostic features. GCDFP-15 expression is further a frequent feature of AR
      positive tumors and the molecular apocrine subtype. It might have reduced
      sensitivity as a diagnostic marker for mammary differentiation in triple negative
      tumors as compared to HR or HER2 positive tumor types.

PMID- 25070174
TI  - Serial magnetic resonance imaging changes in sporadic Creutzfeldt-Jakob disease
      with valine homozygosity at codon 129 of the prion protein gene.

PMID- 25070175
TI  - Use of psychotropic drugs in Lombardy in time of economic crisis (2007-2011): a
      population-based study of adult employees.
AB  - Over years, there has been an increase in the prescription of psychotropic drugs
      (PDs), particularly antidepressants (ADs). The aim of the study was to evaluate
      the consumption of PDs in adult employees in a productive area of Italy and the
      possible changes induced by the "economic crisis". The study is a retrospective
      survey in all adult employees in Lombardy, Northern Italy, aged >18 years in the
      period 2007-2011, classified by gender, age class, nationality, education and
      province. During the 5-year period, there were 3,554,860 employed adults in
      Lombardy, of whom 277,865 (7.8%) used PDs. The use of PDs (particularly ADs) was
      associated with being an Italian woman aged >55 years with a basic education, a
      blue collar job, and an unstable working position. In 39% of cases, the use of
      PDs was limited to one trimester. The increase in the number of prescriptions of
      PDs after the economic crisis was the same as before it. The increase in PD use
      can be attributed more to ADs and anti-epileptic drugs with anxiolytic
      properties. Although continuously increasing, the use of AD fluctuated and was
      greater during the fall and winter. The increase involved all the provinces in
      Lombardy in a similar manner. 

PMID- 25070176
TI  - A baseline controlled examination of a 5-day intensive treatment for pediatric
      obsessive-compulsive disorder.
AB  - This study extends support for a 5-day intensive exposure and response prevention
      (ERP) treatment protocol for pediatric obsessive compulsive disorder (OCD).
      Twenty-two children with OCD received ERP treatment twice daily for 5 days. The
      treatment also emphasized teaching children and parents how to conduct ERP
      independently after they returned home. Symptoms were assessed at four time
      points: Baseline, 4 weeks later at pre-treatment, one week after the intensive
      treatment 5-day treatment, and at 3 month follow-up. Changes on the primary
      outcome measure, clinician severity ratings on the Anxiety Disorders Interview
      Schedule for Children, and secondary measures, indicated that OCD symptoms
      remained stable from the evaluation to baseline and improved significantly from
      baseline to follow-up. Moreover, parental accommodation of OCD decreased
      significantly from baseline to post-treatment and from post-treatment to follow
      up. These data suggest that the 5-day intervention demonstrates efficacy in
      reducing OCD symptoms and may initiate change in parent accommodation that
      continues to improve after the family returns home. 

PMID- 25070177
TI  - How do you feel? Detection of recurrent Major Depressive Disorder using a single
      item screening tool.
AB  - Mood is a key element of Major Depressive Disorder (MDD), and is perceived as a
      highly dynamic construct. The aim of the current study was to examine whether a
      single-item mood scale can be used for mood monitoring. One hundred thirty
      remitted out-patients were assessed using the Structured Clinical Interview for
      DSM-IV Axis-I Disorders (SCID-I), Visual Analogue Mood Scale (VAMS), 17-item
      Hamilton Depression Rating Scale (HAM-D17), and Inventory of Depressive
      Symptomatology-Self Report (IDS-SR). Of all patients, 13.8% relapsed during
      follow-up assessments. Area under the curves (AUCs) for the VAMS, HAM-D17 and IDS
      SR were 0.94, 0.91, and, 0.86, respectively. The VAMS had the highest positive
      predictive value (PPV) without any false negatives at score 55 (PPV=0.53;
      NPV=1.0) and was the best predictor of current relapse status (variance explained
      for VAMS: 60%; for HAM-D17: 49%; for IDS-SR: 34%). Only the HAM-D17 added
      significant variance to the model (7%). Assessing sad mood with a single-item
      mood scale seems to be a straightforward and patient-friendly avenue for life
      long mood monitoring. Using a diagnostic interview (e.g., the SCID) in case of a
      positive screen is warranted. Repeated assessment of the VAMS using Ecological
      Momentary Assessment (EMA) might reduce false positives. 

PMID- 25070179
TI  - Facile fabrication of three-dimensional graphene foam/poly(dimethylsiloxane)
      composites and their potential application as strain sensor.
AB  - A three-dimensional (3D) graphene foam (GF)/poly(dimethylsiloxane) (PDMS)
      composite was fabricated by infiltrating PDMS into 3D GF, which was synthesized
      by chemical vapor deposition (CVD) with nickel foam as template. The electrical
      properties of the GF/PDMS composite under bending stress were investigated,
      indicating the resistance of the GF/PDMS composite was increased with the bending
      curvature. To improve the bending sensitivity of the GF/PDMS composite, a thin
      layer of poly(ethylene terephthalate) (PET) was introduced as substrate to form
      double-layer GF/PDMS-PET composite, whose measurements showed that the resistance
      of the GF/PDMS-PET composite was still increased when bended to the side of PET,
      whereas its resistance would be decreased when bended to the side of GF. For both
      cases, the absolute value of the relative variation of electrical resistance was
      increased with the bending curvature. More importantly, the relative variation of
      electrical resistance for double-layer GF/PDMS-PET composite can be up to six
      times higher than single-layer GF/PDMS composite for the same bending curvature.
      These observations were further supported by the principle of mechanics of
      material. The 3D GF/PDMS-PET composite also has higher flexibility and
      environment stability and can be utilized as a strain sensor with high
      sensitivity, which can find important applications in real-time monitoring of
      buildings, such as a bridge, dam, and high-speed railway. 

PMID- 25070178
TI  - High force development augments skeletal muscle signalling in resistance exercise
      modes equalized for time under tension.
AB  - How force development and time under tension (TUT) during resistance exercise
      (RE) influence anabolic signalling of skeletal muscle is incompletely understood.
      We hypothesized that high force development during RE is more important for post
      exercise-induced signalling than submaximal and fatiguing RE with lower force
      development but similar TUT. Twenty-two male subjects (24 +/- 6 years, 181 +/- 9
      cm, 79 +/- 2 kg) performed three distinct RE modes in the fed state with equal
      TUT but distinct force output: (i) maximal eccentric RE (ECC, n = 7) three sets,
      eight reps, 100% eccentric dynamic force; (ii) standard RE (STD, n = 7), three
      sets, 10 reps, 75% dynamic force; and (iii) high fatiguing single-set RE (HIT, n
      = 8), 20 reps, 100% eccentric-concentric force; vastus lateralis biopsies were
      collected at baseline, 15, 30, 60, 240 min and 24 h after RE, and the signalling
      of mechanosensitive and mammalian target of rapamycin (mTOR)-related proteins was
      determined. The phosphorylation levels of pFAK(Tyr397), pJNK(Thr183/Tyr185),
      pAKT(Thr308/Ser473), pmTOR(Ser2448), p4E-BP1(Thr37/46),
      p70s6k(Thr389)/(Ser421/Thr424) and pS6(Ser235/236) were significantly higher in
      ECC than those in STD and HIT at several time points (P < 0.01).
      pJNK(Thr183/Tyr185) and pS6(Ser235/236) levels were significantly higher in type
      II myofibres in ECC compared with STD and HIT. HIT exerted throughout the weakest
      signalling response. We conclude that high force development during acute RE is
      superior for anabolic skeletal muscle signalling than fatiguing RE with lower
      force output but similar TUT. Our results suggest that this response is
      substantially driven by the higher activation of type II myofibres during RE.

PMID- 25070180
TI  - Screening and identification of small molecule inhibitors of ErbB2-induced
      invasion.
AB  - ERBB2 amplification and overexpression are strongly associated with invasive
      cancer with high recurrence and poor prognosis. Enhanced ErbB2 signaling induces
      cysteine cathepsin B and L expression leading to their higher proteolytic
      activity (zFRase activity), which is crucial for the invasion of ErbB2-positive
      breast cancer cells in vitro. Here we introduce a simple screening system based
      on zFRase activity as a primary readout and a following robust invasion assay and
      lysosomal distribution analysis for the identification of compounds that can
      inhibit ErbB2-induced invasion. With an unbiased kinase inhibitor screen, we
      identified Bohemine/Roscovitine, Go6979 and JAK3 inhibitor VI as compounds that
      can efficiently decrease cysteine cathepsin activity. Using the well-established
      and clinically relevant ErbB1 and ErbB2 inhibitor lapatinib as a positive
      control, we studied their ability to inhibit ErbB2-induced invasion in 3
      dimensional Matrigel cultures. We found one of them, JAK3 inhibitor VI, capable
      of inhibiting invasion of highly invasive ErbB2-positive ovarian cancer cells as
      efficiently as lapatinib, whereas Go6979 and Roscovitine displayed more modest
      inhibition. All compounds reversed the malignant, ErbB2-induced and invasion
      supporting peripheral distribution of lysosomes. This effect was most evident for
      lapatinib and JAK3 inhibitor VI and milder for Go6979 and Roscovitine. Our
      results further showed that JAK3 inhibitor VI function was independent of JAK
      kinases but involved downregulation of cathepsin L. We postulate that the
      screening method and the verification experiments that are based on oncogene
      induced changes in lysosomal hydrolase activity and lysosomal distribution could
      be used for identification of novel inhibitors of ErbB2-induced invasiveness.
      Additionally, we introduce a novel function for lapatinib in controlling
      malignant lysosomal distribution, that may also be involved in its capability to
      inhibit ErbB2-induced invasion in vivo. 

PMID- 25070181
TI  - The effects of nutrition-induced abnormal food metabolism in the Southern Plains
      woodrat (Neotoma micropus): comparisons of variations of the Western diet.
AB  - We investigated the effects of several modifications of the Western diet on a
      medium-sized rodent, Neotoma micropus, that lives in the area of the wildland
      urban interface. We conducted a laboratory study of the response of N. micropus
      to high fat-high fructose (HFHF), high fat-high sucrose (HFHS), high fat-low
      sugar (HFLSu) and control (low fat-low sugar) diets. We found a significant
      increase in hepatic lipid deposition and a significant decrease in podocytes in
      those animals that consumed the HFHF and HFLSu diets compared to those on the
      HFHS and control diets. We found no significant differences in Bowman's space or
      hepatic collagen formation. We predict that N. micropus in the wild, with access
      to anthropogenic resources, will show similar effects as a result of the
      consumption of anthropogenic resources. 

PMID- 25070182
TI  - Test result communication in primary care: clinical and office staff
      perspectives.
AB  - OBJECTIVE: To understand how the results of laboratory tests are communicated to
      patients in primary care and perceptions on how the process may be improved.
      DESIGN: Qualitative study employing staff focus groups. SETTING: Four UK primary
      care practices. PARTICIPANTS: Staff involved in the communication of test
      results. FINDINGS: Five main themes emerged from the data: (i) the default method
      for communicating results differed between practices; (ii) clinical impact of
      results and patient characteristics such as anxiety level or health literacy
      influenced methods by which patients received their test result; (iii) which
      staff member had responsibility for the task was frequently unclear; (iv)
      barriers to communicating results existed, including there being no system or
      failsafe in place to determine whether results were returned to a practice or
      patient; (v) staff envisaged problems with a variety of test result communication
      methods discussed, including use of modern technologies, such as SMS messaging or
      online access. CONCLUSIONS: Communication of test results is a complex yet core
      primary care activity necessitating flexibility by both patients and staff.
      Dealing with the results from increasing numbers of tests is resource intensive
      and pressure on practice staff can be eased by greater utilization of electronic
      communication. Current systems appear vulnerable with no routine method of
      tracing delayed or missing results. Instead, practices only become aware of
      missing results following queries from patients. The creation of a test
      communication protocol for dissemination among patients and staff would help
      ensure both groups are aware of their roles and responsibilities.

PMID- 25070183
TI  - Administration of a plasmid that expresses SDF-1alpha affects the oncogenic
      potential of mouse bcr-abl-transformed cells.
AB  - Stromal-derived factor 1alpha (SDF-1alpha, also known as CXCL12) is a chemokine
      that exerts its effects through the G-protein coupled receptors, C-X-C chemokine
      receptor type 4 (CXCR4) and 7 (CXCR7). There is marked evidence that the SDF
      1/CXCR4 axis is involved in the pathogenesis of leukemia and therapies that
      target this axis are under development. The present study aimed to increase the
      efficacy of a DNA-based bcr-abl vaccine by simultaneously immunizing mice with a
      plasmid carrying the whole SDF-1alpha gene. Bcr-abl-transformed 12B1 cells were
      used to challenge the mice. These cells have the oncogenic potential to induce
      both leukemia following intravenous inoculation and lymphoma-type solid tumors
      after subcutaneous inoculation. Administering an SDF-1 carrying plasmid together
      with the bcr-abl vaccine resulted in increased survival following a challenge
      with subcutaneously administered 12B1 cells, although the difference was not
      statistically significant. However, there was a difference when the animals that
      developed subcutaneous tumors were only taken into consideration. In doubly
      treated mice, significantly more mice failed to develop solid tumors than mice
      that had only received the bcr-abl vaccine. By contrast, the occurrence of fatal
      leukemia was significantly higher in the mice that were treated with the SDF-1
      plasmid, regardless of whether they were immunized with the bcr-abl-vaccine. No
      humoral or cellular immune responses against SDF-1 were detected in the treated
      mice, which suggested that the changes in oncogenic potential of 12B1 cells were
      due to the activity of SDF-1 itself.

PMID- 25070184
TI  - DNA methylation maintenance consolidates RNA-directed DNA methylation and
      transcriptional gene silencing over generations in Arabidopsis thaliana.
AB  - In plants, 24 nucleotide short interfering RNAs serve as a signal to direct
      cytosine methylation at homologous DNA regions in the nucleus. If the targeted
      DNA has promoter function, this RNA-directed DNA methylation may result in
      transcriptional gene silencing. In a genetic screen for factors involved in RNA
      directed transcriptional silencing of a ProNOS-NPTII reporter transgene in
      Arabidopsis thaliana, we captured alleles of DOMAINS REARRANGED METHYLTRANSFERASE
      2, the gene encoding the DNA methyltransferase that is mainly responsible for de
      novo DNA methylation in the context of RNA-directed DNA methylation.
      Interestingly, methylation of the reporter gene ProNOS was not completely erased
      in these mutants, but persisted in the symmetric CG context, indicating that RNA
      directed DNA methylation had been consolidated by DNA methylation maintenance.
      Taking advantage of the segregation of the transgenes giving rise to ProNOS short
      interfering RNAs and carrying the ProNOS-NPTII reporter in our experimental
      system, we found that ProNOS DNA methylation maintenance was first evident after
      two generations of ongoing RNA-directed DNA methylation, and then increased in
      extent with further generations. As ProNOS DNA methylation had already reached
      its final level in the first generation of RNA-directed DNA methylation, our
      findings suggest that establishment of DNA methylation at a particular region may
      be divided into distinct stages. An initial phase of efficient, but still fully
      reversible, de novo DNA methylation and transcriptional gene silencing is
      followed by transition to efficient maintenance of cytosine methylation in a
      symmetric sequence context accompanied by persistence of gene silencing. 

PMID- 25070185
TI  - Carbon-monoxide-releasing molecules for the delivery of therapeutic CO in vivo.
AB  - The development of carbon-monoxide-releasing molecules (CORMs) as pharmaceutical
      agents represents an attractive and safer alternative to administration of
      gaseous CO. Most CORMs developed to date are transition-metal carbonyl complexes.
      Although such CORMs have showed promising results in the treatment of a number of
      animal models of disease, they still lack the necessary attributes for clinical
      development. Described in this Minireview are the methods used for CORM
      selection, to date, and how new insights into the reactivity of metal-carbonyl
      complexes in vivo, together with advances in methods for live-cell CO detection,
      are driving the design and synthesis of new CORMs, CORMs that will enable
      controlled CO release in vivo in a spatial and temporal manner without affecting
      oxygen transport by hemoglobin. 

PMID- 25070186
TI  - Feasibility of occurrence of different types of protonated base pairs in RNA: a
      quantum chemical study.
AB  - Protonated nucleobases have significant roles in facilitating catalytic functions
      of RNA, and in stabilizing different structural motifs. Reported pKa values of
      nucleobase protonation suggest that the population of neutral nucleobases is
      10(3)-10(4) times higher than that of protonated nucleobases under physiological
      conditions (pH ~ 7.4). Therefore, a molecular level understanding of various
      putative roles of protonated nucleobases cannot be achieved without addressing
      the question of how their occurrence propensities and stabilities are related to
      the free energy costs associated with the process of protonation under
      physiological conditions. With water as the proton donor, we use advanced QM
      methods to evaluate the site specific protonation propensities of nucleobases in
      terms of their associated free energy changes (DeltaGprot). Quantitative follow
      up on the energetics of base pair formation and database search for evaluating
      their occurrence frequencies, reveal a lack of correlation between base pair
      stability and occurrence propensities on the one hand, and ease of protonation on
      the other. For example, although N7 protonated adenine (DeltaGprot = 40.0 kcal
      mol(-1)) is found to participate in stable base pairing, base pairs involving N7
      protonated guanine (DeltaGprot = 36.8 kcal mol(-1)), on geometry optimization,
      converge to a minima where guanine transfers its extra proton to its partner
      base. Such observations, along with examples of weak base pairs involving N3
      protonation of cytosine (DeltaGprot = 37.0 kcal mol(-1)) are rationalized by
      analysing the protonation induced charge redistributions which are found to
      significantly influence, both positively and negatively, the hydrogen bonding
      potentials of different functional sites of individual nucleobases. Protonation
      induced charge redistribution is also found to strongly influence (i) the
      aromatic character of the rings of the participating bases and (ii) hydrogen
      bonding potential of the free edges of the protonated base pair. Comprehensive
      analysis of a non-redundant RNA crystal structure dataset further reveals that,
      while availability of stabilization possibilities determine the feasibility of
      occurrence of protonated bases, their occurrence context and specific functional
      roles are important factors determining their occurrence propensities. 

PMID- 25070187
TI  - Inter-vendor variability of left ventricular volumes and strains determined by
      three-dimensional speckle tracking echocardiography.
AB  - BACKGROUND: Inter-vendor discordance in three-dimensional speckle-tracking
      echocardiography (3DS) remains uncharacterized. We aimed to examine inter-vendor
      discordance of left ventricular (LV) volumes, and functional parameters and their
      reproducibilities between two commercially available 3DS systems. METHODS:
      Echocardiographic examinations with 3DS were performed in 26 healthy subjects
      (age 34 +/- 13 years, 85% men) using a Vivid E9 system (V1) with 4V probe (GE
      Health Care) and Artida (V2) with PST-25SX probe (Toshiba Medical Systems) on the
      same day. LV variables and global LV longitudinal, circumferential, radial, and
      area strains were measured by vendor-specific softwares, 4D strain EchoPAC BT11
      (for V1) and 3D WMT (for V2), respectively. Reproducibility of data was assessed
      by an intra-class correlation coefficient (ICC). RESULTS: The mean time required
      for 3DS analysis was 5.4 +/- 1.5 min for V1, being 21% less than that for V2 (6.8
      +/- 1.9 min, P < 0.01). Reproducibilities of all LV strains were comparable
      between V1 (ICC 0.50-0.82) and V2 (ICC 0.51-0.76), except for intra-observer and
      inter-observer reproducibilities of radial strain being lower in V2 (ICC for V1
      0.82 and 0.82 and ICC for V2 0.44 and 0.40, respectively). LV strains in all
      directions and area were significantly different between V1 and V2, though LV
      volumes and ejection fraction were comparable. CONCLUSIONS: Global longitudinal,
      circumferential, and area LV strains are reproducible in both 3DS vendors.
      However, values of three-dimensional LV strains by 3DS are highly vendor
      dependent.

PMID- 25070188
TI  - IgE and IL-33-mediated triggering of human basophils inhibits TLR4-induced
      monocyte activation.
AB  - Basophils are circulating granulocytes, best known as effector cells in allergic
      reactions. Recent studies in mice suggest that they might also participate in the
      suppression of chronic inflammation. The aim of this study was to assess the
      ability of purified human basophils to modulate monocyte responses upon IL-33 and
      IgE triggering. Activation of human basophils with IL-33 induced the production
      of IL-4 and the release of histamine, and enhanced their IgE-mediated activation.
      In addition, basophils triggered with IL-33 and anti-IgE significantly suppressed
      the LPS-induced production of the proinflammatory cytokine TNF-alpha and the
      upregulation of the costimulatory molecule CD80 by monocytes. These effects were
      mainly explained by the release of histamine, as they could be inhibited by the
      histamine receptor 2 antagonist ranitidine, with a smaller contribution of IL-4.
      In contrast, basophil-derived IL-4 and histamine had opposing effects on the
      expression of the inhibitory Fc gamma receptor IIb and the production of IL-10 by
      monocytes. Our data show that basophils can influence monocyte activation and
      suggest a previously unrecognized role for human basophils in the modulation of
      monocyte-mediated immune responses, through the balanced secretion of histamine
      and IL-4. 

PMID- 25070189
TI  - Pilot study to assess the influence of an enhanced medication plan on patient
      knowledge at hospital discharge.
AB  - PURPOSE: This study assessed the effect of providing an enhanced medication plan
      (EMP) to patients during patient-physician conversation at hospital discharge and
      evaluated its immediate impact on patient knowledge on pharmacotherapy. METHODS:
      We observed patient-physician conversations at hospital discharge in three
      internal medicine wards of the University Hospital Heidelberg before and after
      the EMP was integrated into the discharge process, and documented how and to what
      extent physicians provided the patients with drug information. After the
      conversation, the patients' knowledge was evaluated by three standardized
      questions about their pharmacotherapy. RESULTS: We observed 90 conversations (50
      before EMP-implementation, 40 after). In both phases, the conversation duration
      was 5.6-6 min (p = 0.56). However, the time spent on drug information increased
      significantly by 61.7% after EMP-implementation (+63 s, p = 0.02). Before
      implementation, physicians gave at least one drug administration recommendation
      for 75.1% of all drugs, compared to 84.6% after implementation (p = 0.02). The
      EMP provided information for almost all drugs (98.9%; p < 0.01) after
      implementation. Three times more patients answered all questions correctly after
      EMP-implementation (p < 0.01). CONCLUSION: The provision of an EMP improves
      information transfer and therefore increases the patients' knowledge of their
      individual drug treatment without prolonging the overall discharge process.

PMID- 25070191
TI  - Evaluation of the initiation of urine drug screens intended for use in transfer
      patients.
AB  - OBJECTIVE: The objective of this study was to determine if signs of clinical
      intoxication were present in patients who had transfer urine drug screens (UDS)
      performed and to determine the proportion of patients with UDS orders who were
      actually transferred to another facility. METHODS: Of all emergency department
      (ED) patient visits who had a transfer UDS ordered from November 19, 2011, to
      December 31, 2012, 54% of the population was randomly selected for review by 1 of
      3 study investigators. For quality assurance, a random sample of 100 patient
      charts was independently reviewed by all 3 investigators to assure consistency in
      interpreting data. Demographics, clinical characteristics and history,
      disposition, and laboratory results were recorded. RESULTS: Of the 639 patients
      included in this study, only 18% were transferred to another psychiatric
      facility. Pediatric patients and those with presenting with suicidal ideation
      were more likely to be transferred to an outside facility. Thirty-six percent of
      the UDS were positive for at least one substance. Marijuana was the most common
      substance (23%), followed by cocaine (7%) and opiates (7%). There was no evidence
      that the UDS changed acute management decisions. CONCLUSIONS: Few (<6%) patients
      demonstrated any clinical characteristics that were consistent with an acute
      intoxication. Less than 20% of patients who had a transfer UDS were actually
      transferred to an outside facility corresponding with more than 80% not ordered
      appropriately according to the ED established guidelines. This number of
      inappropriate tests represented more than $152 000 of avoidable UDS cost during
      the study period.

PMID- 25070190
TI  - Anti-inflammatory activity of extracts of Bushen-Qiangdu-Zhilv decoction, a
      Chinese medicinal formula, in M1-polarized RAW264.7.
AB  - BACKGROUND: Bushen-Qiangdu-Zhilv Decoction (BQZ) is one of famous traditional
      Chinese medical formula for treating ankylosing spondylitis (AS). However, the
      mechanisms underlying effects of BQZ remains unknown. Pro-inflammatory cytokines,
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-1, play an important role
      in AS. We therefore evaluated if BQZ could affect the expression of these
      cytokines. METHODS: Crude extracts were prepared and fractioned with petroleum
      ether (PE), ethyl acetate (EA), n-butanol (BU) and finally water (ACE). The
      stability of the extracts was confirmed by high-pressure liquid chromatography
      (HPLC) analysis. M1-polarized RAW264.7 was induced and subsequently treated with
      BQZ extracts. Quantitative real-time PCR experiments were performed to measure
      mRNA expression of TNF-alpha and IL-1. RESULTS: It was found that TNF-alpha could
      be significantly suppressed by ACE extracts, whereas IL-1 was dramatically
      inhibited by BU extracts, which was further confirmed by dose-dependent
      experiments. Importantly, MTS assays showed that both ACE and BU extracts had a
      low cytotoxicity. CONCLUSION: Altogether, our study indicates that BQZ decoction
      exerts anti-AS effects via its anti-inflammatory activity and may have a low side
      effect. Further analysis of the extracts of BQZ decoction could lead to a
      discovery of some novel drugs adding to therapeutic strategy for AS patients.

PMID- 25070192
TI  - Spontaneous spinal epidural abscess in a 21-month-old child.
AB  - Spontaneous epidural abscess formation is a rare finding in all populations and
      even more so in the pediatric population. Its rarity and varied presentations
      often lead to misdiagnosis. We present a pediatric case in which the diagnosis of
      spontaneous spinal epidural abscess was missed upon initial presentation and
      subsequently identified at a later visit to the emergency department. Literature
      suggests utilizing three simple physical exam findings that may improve the first
      visit diagnosis of spontaneous epidural abscesses in children. Findings of any
      two of the following signs should guide the clinician to consider SEA as a
      possibility prior to discharge: fever, back or neck pain, extremity weakness or
      inability to walk.

PMID- 25070193
TI  - Successful resuscitation with thrombolysis of pulmonary embolism due to
      thrombotic thrombocytopenic purpura during cardiac arrest.
AB  - Our case describes an episode of fulminant pulmonary embolism (PE) due to
      thrombotic thrombocytopenic purpura, which was accompanied by cardiac arrest. A
      33-year-old woman was transferred to intensive care unit who had severe dyspnea
      with microangiopathic hemolytic anemia. After intubated with ventilation support,
      the patient's symptoms were exacerbated with cardiac arrest from the narrow QRS
      complex pulseless electrical activity. With an initially unsuccessful
      cardiopulmonary resuscitation period of 56 minutes, spontaneous circulation
      returned after a bolus injection of recombinant tissue plasminogen activator. The
      patient became awake and alert without any complication and sequel through
      successive treatment. We conclude that thrombotic thrombocytopenic purpura is a
      medical emergency with severe hematologic disorder with a high risk of PE
      especially within 24 hours after the episodes of hemolysis. Empiric thrombolysis
      during cardiopulmonary resuscitation in presumed fulminant PE can be highly
      beneficial with better survival rates and neurologic outcome.

PMID- 25070194
TI  - Sore throat may be a clue to the early diagnosis of spontaneous
      pneumomediastinum.
AB  - Spontaneous pneumomediastinum is defined as presence of air in the mediastinum
      without obvious cause such as esophageal perforation or abscess formation. It is
      a benign condition and usually resolved by itself in 1 to 2 weeks. The main
      symptom of spontaneous pneumomediastinum is retrosternal chest pain. Here, we
      present a young adult who complained about sore throat initially. Marked
      retropharyngeal emphysema was noted by neck x-ray. Pneumomediastinum was
      confirmed with chest x-ray and computed tomographic scan later on.We want to
      emphasize the importance of thorough history taking and lateral soft tissue neck
      radiograph on retropharyngeal emphysema in real time, which is key to the
      diagnostic workup for patients who present with persistent sore throat and
      dysphagia in young adult.

PMID- 25070196
TI  - Expression of recombinant alpha and beta tubulins from the yew Taxus cuspidata
      and analysis of the microtubule assembly in the presence of taxol.
AB  - Taxol was originally isolated from the yew Taxus brevifolia. Because taxol
      inhibits the depolymerization of microtubules, the presence of a self-resistance
      mechanism in Taxus spp. was hypothesized. The cloning of the cDNA for alpha and
      beta tubulins from Taxus cuspidata and those from the human embryonic kidney cell
      line HEK293T revealed that the (26)Asp, (359)Arg, and (361)Leu residues in the
      human beta tubulin, which are important for taxol binding, were replaced with
      Glu, Trp, and Met in the beta tubulin of T. cuspidata, respectively. The
      microtubule assembly of the recombinant alpha and beta tubulins was monitored
      turbidimetrically, and the results clearly demonstrated that the microtubule from
      T. cuspidata is less sensitive to taxol than that from HEK293T cells. The Taxus
      microtubule composed of the wild-type alpha tubulin and the beta tubulin with the
      E26D mutation restored the sensitivity to taxol. We thus postulated that the
      mutation identified in the beta tubulin of T. cuspidata plays a role in the self
      resistance of this species against taxol.

PMID- 25070205
TI  - Freeze-drying-assisted synthesis of hierarchically porous carbon/germanium hybrid
      for high-efficiency lithium-ion batteries.
AB  - Herein, an approach is reported to prepare porous a carbon/Ge (C/Ge) hybrid. In
      this hybrid, Ge nanoparticles are closely embedded in a highly conductive and
      flexible carbon matrix. Such a hybrid features a high surface area (128.0 m(2) g(
      1)) and a hierarchical micropore-mesopore structure. When used as an anode
      material in lithium-ion batteries (LIBs), the as-prepared hybrid [C/Ge (60.37%)]
      exhibits an improved lithium storage performance with regard to its capacity and
      rate capability compared to its counterparts. More specifically, it can maintain
      a specific capacity as high as 906 mAh g(-1) at a high current density of 0.6 A
      g(-1) after 50 cycles. The excellent lithium storage performance of the C/Ge
      (60.37%) sample can be attributed to synergetic effects between the carbon matrix
      and Ge nanoparticles. The method we adopted is simple and effective, and can be
      extended to fabricate other nanomaterials.

PMID- 25070206
TI  - The anatomical relationship between the roots of mandibular second molars and the
      inferior alveolar nerve.
AB  - AIM: To evaluate the anatomical relationship between the roots of mandibular
      second molars and the inferior alveolar nerve (IAN) in relation to the risk of
      potential nerve injury during root canal treatment. METHODOLOGY: Cone-beam
      computed tomography (CBCT) images from the patient record database at a dental
      hospital were selected. The anonymized CBCT images were reconstructed and
      examined in three planes (coronal, axial and sagittal) using 3D viewing software.
      The relationship between each root apex of mandibular second molars and the IAN
      was evaluated by measuring the horizontal and vertical distances from coronal
      CBCT sections, and the actual distance was then calculated mathematically using
      Pythagoras' theorem. RESULTS: In 55% of the 272 mandibular second molar roots
      evaluated, from a total of 134 scans, the distance between the anatomical root
      apex and the IAN was <=3 mm. CONCLUSIONS: In over 50% of the cases evaluated,
      there was an intimate relationship between the roots of mandibular second molars
      and the inferior alveolar nerve (IAN). Therefore, root canal treatment of
      mandibular second molars may pose a more significant potential risk of IAN
      injury; necessary precautions should be exercised, and the prudent use of CBCT
      should be considered if an intimate relationship is suspected.

PMID- 25070207
TI  - The role of middle latency evoked potentials in early prediction of favorable
      outcomes among patients with severe ischemic brain injuries.
AB  - OBJECTIVE: To explore the role of middle latency evoked potentials (EPs) as
      predictors for favorable outcome in patients with severe ischemic brain injuries
      by comparing the prognostic ability of short latency somatosensory and auditory
      evoked potentials (SLSEP and BAEP) with middle latency somatosensory and auditory
      evoked potentials (MLSEP and MLAEP). METHODS: MLSEP, MLAEP, SLSEP and BAEP were
      recorded in 112 patients with severe ischemic brain injuries (Glasgow Coma Scale
      <= 8). Among them, 83 patients suffered from cerebral ischemic stroke and 29
      suffered from anoxic-ischemic encephalopathy after cardiopulmonary resuscitation
      between 1 and 7 days after the onset of stroke. Outcomes were reviewed 6 months
      later using the Glasgow Outcome Scale (GOS). A GOS score of 4-5 was considered as
      a good outcome while a score of 1-3 was considered as poor. RESULTS: By using the
      prognostic authenticity analysis of predictors for good outcome, at least
      unilateral N20 of the SLSEP exit and at least unilateral N60 of the MLSEP exit
      showed the highest sensitivity which was 100% (95% CI: 86.7%-100%). The bilateral
      normal N60 showed a high specificity of 97.5% (95% CI: 90.4%-99.6%). It also
      showed the highest positive likelihood ratio of 6.25% (95% CI: 1.28%-30.59%),
      which was superior to N20 of SLSEP, V of BAEP, and Pa of MLAEP. The analysis
      demonstrated that the area under the curve for MLSEP grading was the highest
      (0.838) compared to that of SLSEP grading (0.784), MLAEP grading (0.659) and BAEP
      grading (0.621). CONCLUSIONS: Compared with using N20 of SLSEP analysis alone,
      adding MLSEP improves the outcome prediction in patients with severe ischemic
      brain injuries. When an outcome is uncertain after initial evaluation using short
      latency EPs, MLSEP is valuable to be used from the first week to further improve
      prognostication in these patients.

PMID- 25070209
TI  - Impact of cardiovascular risk factors on medical expenditure: evidence from
      epidemiological studies analysing data on health checkups and medical insurance.
AB  - Concerns have increasingly been raised about the medical economic burden in
      Japan, of which approximately 20% is attributable to cardiovascular disease,
      including coronary heart disease and stroke. Because the management of risk
      factors is essential for the prevention of cardiovascular disease, it is
      important to understand the relationship between cardiovascular risk factors and
      medical expenditure in the Japanese population. However, only a few Japanese
      epidemiological studies analysing data on health checkups and medical insurance
      have provided evidence on this topic. Patients with cardiovascular risk factors,
      including obesity, hypertension, and diabetes, may incur medical expenditures
      through treatment of the risk factors themselves and through procedures for
      associated diseases that usually require hospitalization and sometimes result in
      death. Untreated risk factors may cause medical expenditure surges, mainly due to
      long-term hospitalization, more often than risk factors preventively treated by
      medication. On an individual patient level, medical expenditures increase with
      the number of concomitant cardiovascular risk factors. For single risk factors,
      personal medical expenditure may increase with the severity of that factor.
      However, on a population level, the medical economic burden attributable to
      cardiovascular risk factors results largely from a single, particularly prevalent
      risk factor, especially from mildly-to-moderately abnormal levels of the factor.
      Therefore, cardiovascular risk factors require management on the basis of both a
      cost-effective strategy of treating high-risk patients and a population strategy
      for reducing both the ill health and medical economic burdens that result from
      cardiovascular disease. 

PMID- 25070210
TI  - Fetal QRS detection and heart rate estimation: a wavelet-based approach.
AB  - Fetal heart rate monitoring is used for pregnancy surveillance in obstetric units
      all over the world but in spite of recent advances in analysis methods, there are
      still inherent technical limitations that bound its contribution to the
      improvement of perinatal indicators. In this work, a previously published wavelet
      transform based QRS detector, validated over standard electrocardiogram (ECG)
      databases, is adapted to fetal QRS detection over abdominal fetal ECG. Maternal
      ECG waves were first located using the original detector and afterwards a version
      with parameters adapted for fetal physiology was applied to detect fetal QRS,
      excluding signal singularities associated with maternal heartbeats. Single lead
      (SL) based marks were combined in a single annotator with post processing rules
      (SLR) from which fetal RR and fetal heart rate (FHR) measures can be computed.
      Data from PhysioNet with reference fetal QRS locations was considered for
      validation, with SLR outperforming SL including ICA based detections. The error
      in estimated FHR using SLR was lower than 20 bpm for more than 80% of the
      processed files. The median error in 1 min based FHR estimation was 0.13 bpm,
      with a correlation between reference and estimated FHR of 0.48, which increased
      to 0.73 when considering only records for which estimated FHR > 110 bpm. This
      allows us to conclude that the proposed methodology is able to provide a
      clinically useful estimation of the FHR. 

PMID- 25070208
TI  - Relationship between physical activity and chronic musculoskeletal pain among
      community-dwelling Japanese adults.
AB  - BACKGROUND: Both little and excessive physical activity (PA) may relate to
      chronic musculoskeletal pain. The primary objective of this study was to
      characterize the relationship of PA levels with chronic low back pain (CLBP) and
      chronic knee pain (CKP). METHODS: We evaluated 4559 adults aged 40-79 years in a
      community-based cross-sectional survey conducted in 2009 in Shimane, Japan. We
      used self-administered questionnaires to assess sociodemographics and health
      status: PA was assessed by the International Physical Activity Questionnaire, and
      CLBP and CKP were assessed by a modified version of the Knee Pain Screening Tool.
      We examined relationships of PA with prevalence of CLBP and CKP using Poisson
      regression, controlling for potential confounders. RESULTS: CLBP and CKP were
      both prevalent (14.1% and 10.7%, respectively) and associated with history of
      injury, medication use, and consultation with physicians. PA was not
      significantly related to CLBP or CKP (P > 0.05) before or after adjustment for
      potential confounders. For example, compared with adults reporting moderate PA
      (8.25-23.0 MET-hours/week), prevalence ratios for CKP adjusted for sex, age,
      education years, self-rated health, depressive symptom, smoking, chronic disease
      history, and body-mass index were 1.12 (95% confidential interval [CI] 0.84-1.50)
      among those with the lowest PA and 1.26 (95% CI 0.93-1.70) among those with the
      highest PA (P quadratic = 0.08). The prevalence ratios were further attenuated
      toward the null after additional adjustment for history of injury, medication
      use, and consultation (P quadratic = 0.17). CONCLUSIONS: This cross-sectional
      study showed that there were no significant linear or quadratic relationships of
      self-reported PA with CLBP and CKP. Future longitudinal study with objective
      measurements is needed.

PMID- 25070211
TI  - [Procedural aspects in primary PCI: arterial access, stent selection,
      thrombectomy and treatment of non-culprit lesions].
AB  - Acute myocardial infarction was one of the most common causes of death in Germany
      in 2011. According to the guidelines of the European Society for Cardiology,
      systemic fibrinolysis and primary percutaneous coronary intervention (PCI) are
      the methods of choice for acute treatment. Primary PCI should be given priority
      due to its superiority. The transradial access should be preferred due to the
      lower bleeding complication rate. In the selection of stents the new generation
      of drug-eluting stents (DES) are superior to the first generation of bare metal
      stents (BMS). It has now been demonstrated that the incident rates of DES (e.g.
      mortality, target vessel revascularization, early and late stent thrombosis and
      myocardial infarction) are significantly lower. For bioresorbable scaffolds (BRS)
      long-term results for the use in treatment of ST-elevation myocardial infarction
      (STEMI) are not yet available but initial results are very promising. However,
      the selection of a stent needs to be done on an individual basis in order to do
      justice to all aspects. Data with respect to thrombectomy in acute treatment are
      heterogeneous. Currently, a thorough consideration of all aspects is necessary
      because thrombus aspiration can also be associated with an increased rate of
      incidents. In a state of hemodynamic stability only so-called culprit lesions
      should currently be treated with a stent. Elective interventions on further
      stenoses should be carried out after consideration of individual factors and if
      necessary evaluation of the hemodynamic relevance. 

PMID- 25070213
TI  - Development and validation of the Johns Hopkins Disruptive Clinician Behavior
      Survey.
AB  - Although the negative impact of disruptive clinician behavior on quality health
      care delivery has gained attention recently, little systematic effort to address
      this issue has been reported. To facilitate empirical research to reduce
      disruptive clinician behaviors, an assessment tool (Johns Hopkins Disruptive
      Clinician Behavior Survey [JH-DCBS]) with 5 discrete subscales was developed
      using a 2-step design. First a pool of items was generated from focus group
      studies and the literature, and then a psychometric evaluation of the survey was
      conducted with a sample of clinicians (N = 1198) practicing in a large urban
      academic medical center. The results indicated that the tool was reliable
      (Cronbach alpha = .79-.91), showed high content validity (Content Validity Index
      = .97), and had significantly high correlations with theoretically selected
      variables. The study team concluded that the JH-DCBS provides a valid empirical
      assessment of disruptive behavior. Assessment results may be used to design
      strategies to improve the health and safety of practice environments. 

PMID- 25070212
TI  - Network features suggest new hepatocellular carcinoma treatment strategies.
AB  - BACKGROUND: Resistance to therapy remains a major cause of the failure of cancer
      treatment. A major challenge in cancer therapy is to design treatment strategies
      that circumvent the higher-level homeostatic functions of the robust cellular
      network that occurs in resistant cells. There is a lack of understanding of
      mechanisms responsible for the development of cancer and the basis of therapy
      resistance mechanisms. Cellular signaling networks have an underlying
      architecture guided by universal principles. A robust system, such as cancer, has
      the fundamental ability to survive toxic anticancer drug treatments or a
      stressful environment mainly due to its mechanisms of redundancy. Consequently,
      inhibition of a single component/pathway would probably not constitute a
      successful cancer therapy. RESULTS: We developed a computational method to study
      the mechanisms of redundancy and to predict communications among the various
      pathways based on network theory, using data from gene expression profiles of
      hepatocellular carcinoma (HCC) of patients with poor and better prognosis
      cancers. Our results clearly indicate that immune system pathways tightly
      regulate most cancer pathways, and when those pathways are targeted by drugs, the
      network connectivity is dramatically changed. We examined the main HCC targeted
      treatments that are currently being evaluated in clinical trials. One prediction
      of our study is that Sorafenib combined with immune system treatments will be a
      more effective combination strategy than Sorafenib combined with any other
      targeted drugs. CONCLUSIONS: We developed a computational framework to analyze
      gene expression data from HCC tumors with varying degrees of responsiveness and
      non-tumor samples, based on both Gene and Pathway Co-expression Networks. Our
      hypothesis is that redundancy is one of the major causes of drug resistance, and
      can be described as a function of the network structure and its properties. From
      this perspective, we believe that integration of the redundant variables could
      lead to the development of promising new methodologies to selectively identify
      and target the most significant resistance mechanisms of HCC. We describe three
      mechanisms of redundancy based on their levels of generalization and study the
      possible impact of those redundancy mechanisms on HCC treatments.

PMID- 25070214
TI  - Evaluating the effect of safety culture on error reporting: a comparison of
      managerial and staff perspectives.
AB  - Although medical error reporting has been studied, underreporting remains
      pervasive. The study aims were to identify the organizational factors with the
      greatest perceived effect on error reporting and to determine whether
      associations differ for management and clinical staff. A total of 515 637
      respondents from 1052 hospitals completed the Hospital Survey on Patient Safety
      Culture. Nine organizational factors were tested as predictors of error reporting
      using weighted least-squares multiple regression. Error feedback was perceived as
      the most significant predictor, while organizational learning was another
      significant factor. It also was found that although management support for
      patient safety was significantly related to error reporting among clinical staff,
      this association was not significant among management. This difference is
      relevant because managers may not be aware that their failure to demonstrate
      support for safety leads to underreporting by frontline clinical staff. Findings
      from this study can inform hospitals' efforts to increase error reporting. 

PMID- 25070215
TI  - Thermomonas carbonis sp. nov., isolated from the soil of a coal mine.
AB  - Strain GZ436(T) was Gram-stain-negative, aerobic, non-motile, rod-shaped and
      isolated from the soil of a coal mine. 16S rRNA gene phylogenetic analysis showed
      that this strain clustered with Thermomonas brevis LMG 21746(T) (97.5%),
      Thermomonas haemolytica A50-7-3(T) (96.3%), Thermomonas koreensis KCTC 12540(T)
      (96.4%), Thermomonas hydrothermalis SGM-6(T) (95.5%) and Thermomonas fusca LMG
      21737(T) (95.1%). The major isoprenoid quinone was Q-8. The DNA G+C content was
      67 mol%. Strain GZ436(T) contained phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine, an unknown aminophospholipid, an unknown phospholipid
      and an unknown lipid as the major polar lipids. The predominant cellular fatty
      acids (>5%) were iso-C(15:0), iso-C(11:0), iso-C(11:0 3)-OH, iso-C(17:1)omega9c,
      C(16 : 0) and summed feature 3. The DNA-DNA relatedness value between strain
      GZ436(T) and T. brevis LMG 21746(T) was 54 +/- 0.4%. According to phenotypic and
      phylogenetic characteristics, strain GZ436(T) represents a novel species of the
      genus Thermomonas, for which the name Thermomonas carbonis sp. nov. is proposed.
      The type strain is GZ436(T) ( =CCTCC AB 2013364(T) = KCTC 42013(T)).

PMID- 25070216
TI  - Lysinibacillus varians sp. nov., an endospore-forming bacterium with a filament
      to-rod cell cycle.
AB  - Six Gram-stain-positive, motile, filamentous and/or rod-shaped, spherical spore
      forming bacteria (strains GY32(T), L31, F01, F03, F06 and F07) showing
      polybrominated diphenyl ether transformation were investigated to determine their
      taxonomic status. After spore germination, these organisms could grow more than
      one hundred microns long as intact single cells and then divide into rod cells
      and form endospores in 33 h. The cell-wall peptidoglycan of these strains was
      type A4alpha, the predominant menaquinone was MK-7 and the major fatty acids were
      iso-C(16:0), iso-C(15:0) and C(16:1)omega7C. Diphosphatidylglycerol,
      phosphatidylglycerol and phosphatidylethanolamine were detected in the polar
      lipid profile. Analysis of the 16S rRNA gene sequences indicated that these
      strains should be placed in the genus Lysinibacillus and they were most closely
      related to Lysinibacillus sphaericus DSM 28(T) (99% 16S rRNA gene sequence
      similarity). The gyrB sequence similarity and DNA-DNA relatedness between strain
      GY32(T) and L. sphaericus JCM 2502(T) were 81% and 52%, respectively. The G+C
      content of the genomic DNA of strain GY32(T) was 43.2 mol%. In addition, strain
      GY32(T) showed differences in nitrate reduction, starch and gelatin hydrolysis,
      carbon resource utilization and cell morphology. The phylogenetic distance from
      its closest relative measured by DNA-DNA relatedness and DNA G+C content, and its
      phenotypic properties demonstrated that strain GY32(T) represents a novel species
      of the genus Lysinibacillus, for which the name Lysinibacillus varians sp. nov.
      is proposed. The type strain is GY32(T) ( = NBRC 109424(T) = CGMCC 1.12212(T) =
      CCTCC M 2011307(T)).

PMID- 25070217
TI  - Salimicrobium jeotgali sp. nov., isolated from salted, fermented seafood.
AB  - A Gram-staining-positive, aerobic, motile bacterium, designated strain MJ3(T),
      was isolated from myeolchi-jeot (anchovy jeotgal), a traditional fermented
      seafood in South Korea. Cells were non-endospore-forming cocci showing catalase-
      and oxidase-positive reactions. Growth of strain MJ3(T) was observed at 15-45 
      degrees C (optimum, 30  degrees C), at pH 6.0-9.0 (optimum, pH 7.0-8.0) and in
      the presence of 1-24% (w/v) NaCl (optimum, 10% NaCl). Phylogenetic inference
      based on 16S rRNA gene sequences showed that strain MJ3(T) formed a tight
      phyletic lineage with members of the genus Salimicrobium. Strain MJ3(T) was
      related most closely to Salimicrobium salexigens 29CMI(T), Salimicrobium album
      DSM 20748(T), Salimicrobium flavidum ISL-25(T), Salimicrobium luteum BY-5(T) and
      Salimicrobium halophilum DSM 4771(T), with similarities of 98.8%, 98.7%, 98.6%,
      98.4% and 98.3%, respectively. However, the DNA-DNA relatedness values between
      strain MJ3(T) (KF732837) and S. salexigens DSM 22782(T), S. album DSM 20748(T),
      S. flavidum DSM 23127(T), S. luteum KCTC 3989(T) and S. halophilum JCM 12305(T)
      were 60 +/- 5.4%, 58.5 +/- 6.5%, 43.6 +/- 5.5%, 37.2 +/- 5.8% and 16.7 +/- 0.2%,
      respectively. Chemotaxonomic data (sole isoprenoid quinone, MK-7; major cell-wall
      type, meso-diaminopimelic acid; major cellular fatty acids, anteiso-C15 : 0,
      anteiso-C17 : 0 and iso-C15 : 0; major polar lipids, phosphatidylglycerol and
      diphosphatidylglycerol; DNA G+C content, 46.3 mol%) also supported the
      affiliation of strain MJ3(T) with the genus Salimicrobium. Therefore, strain
      MJ3(T) represents a novel species of the genus Salimicrobium, for which the name
      Salimicrobium jeotgali sp. nov. is proposed. The type strain is MJ3(T) ( = KACC
      16972(T) = JCM 19758(T)).

PMID- 25070218
TI  - Comparative study on immediate versus delayed meniscus allograft transplantation:
      4- to 6-year follow-up.
AB  - BACKGROUND: Meniscus allograft transplantation (MAT) is generally used for
      patients who sustain symptoms after meniscectomy, which could be called delayed
      MAT. Meniscus allograft transplantation for patients immediately after
      meniscectomy has not been reported. HYPOTHESIS: Compared with the conventional
      delayed MAT, immediate MAT might provide better clinical results and reduce joint
      degeneration. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The
      study was performed with 18 transplanted menisci (6 medial, 12 lateral) from 16
      patients. Eight menisci were transplanted immediately after meniscectomy (IM
      group); 10 menisci, from patients who complained of knee symptoms at a mean time
      of 35 months (range, 9-92 months) after total meniscectomy, underwent delayed
      transplantation (DE group). Fourteen patients undergoing meniscectomy during the
      same period were included as controls (ME group). Degenerative changes in knee
      joints were evaluated by plain radiographs and magnetic resonance imaging (MRI).
      Allograft extrusion and relative percentage of extrusion were measured on MRI.
      Other outcome assessments included preoperative and postoperative International
      Knee Documentation Committee (IKDC), Tegner, and Lysholm scores; visual analog
      scale (VAS) for pain; and range of motion and isokinetic muscle strength
      evaluation. RESULTS: The mean length of follow-up was 50.8 months (range, 44-62
      months) for the IM group, 72.0 months (range, 44-94 months) for the DE group, and
      54.3 months (range, 45-62 months) for the ME group. A statistically significant
      difference in favor of the IM and ME groups was found on the VAS (0.4 [IM group]
      vs 1.1 [ME group] vs 2.5 [DE group]) and muscle strength (P < .05). The mean IKDC
      score in the IM group was significantly higher than that in the DE group (93
      [range, 85-99] vs 74 [range, 38-95], respectively; P < .05). The IM group showed
      significantly less preoperative to postoperative cartilage degeneration changes
      on radiographs and MRI when compared with the DE and ME groups (Kellgren-Lawrence
      score changes: 0.25 [IM group] vs 1.0 [DE group] vs 1.7 [ME group]; Yulish score
      changes: 0.25 [IM group] vs 1.0 [DE group] vs 1.1 [ME group]; P < .05). Extrusion
      of the allograft was observed in the body of the menisci in all patients. No
      significant difference was found in terms of the Lysholm score, Tegner score,
      joint narrowing, or meniscus extrusion (P > .05). CONCLUSION: Compared with
      delayed MAT, immediate MAT led to more satisfactory subjective results, less
      joint degeneration, and less muscle strength deficits. The short-term results of
      delayed meniscus transplantation were close to those of meniscectomy.

PMID- 25070219
TI  - Enhanced patella-patellar tendon healing using combined magnetic fields in a
      rabbit model.
AB  - BACKGROUND: A combined magnetic field (CMF) is a composite of a dynamic
      sinusoidal magnetic field and a magnetostatic field. Stimuli from CMFs has proved
      to be an effective tool for healing problem fractures and spinal fusion
      procedures. HYPOTHESIS: Combined magnetic field technology will enhance healing
      of bone-tendon junction repair via endochondral ossification for regeneration of
      the fibrocartilage zone. STUDY DESIGN: Controlled laboratory study. METHODS:
      Forty-eight mature rabbits were randomly divided into CMF-treated and placebo
      treated (control) groups. A partial patellectomy model was created. The CMF
      treated group was subjected to CMF stimulation from the third postoperative day
      for 30 minutes per day up to weeks 8 or 16. At each time point, tissue samples
      were harvested and evaluated biomechanically and histomorphologically. The area
      of newly formed bone and the thickness of fibrocartilage were measured in
      hematoxylin and eosin-stained sections and toluidine blue-stained sections,
      respectively, while the density of fibrocartilage cells and the amount of
      proteoglycans were calculated using safranin O-stained sections. A biomechanical
      analysis was carried out to ascertain tensile strength. RESULTS: Quantitative
      histological measurements showed that the newly formed bone and regenerated
      fibrocartilage zone in the CMF-treated group increased by a respective 99.2% and
      41.9% compared with the control group at week 8 and a respective 97.8% and 22.8%
      at week 16. In the CMF-treated group at postoperative week 16, the amount of
      proteoglycans was 36.9% more than that of the control group, but the density of
      fibrocartilage cells was just 71.4% of the control group; there were no
      significant differences at week 8. Mechanical test results showed that energy to
      failure was not significantly different between the 2 groups at week 8. Yet, at
      week 16, load to failure, ultimate strength, and energy to failure in the CMF
      treated group (311.0 +/- 59.4 N, 8.46 +/- 1.41 MPa, and 0.87 +/- 0.17 J,
      respectively) were significantly higher than those in the control group (247.1 +/
      65.6 N, 6.84 +/- 1.12 MPa, and 0.52 +/- 0.15 J, respectively). CONCLUSION:
      Biophysical stimulation with CMFs enhances healing after bone-tendon junction
      injuries in a rabbit model. CLINICAL RELEVANCE: These results demonstrate the
      feasibility of using CMFs for stimulating bone-tendon healing after repair.

PMID- 25070220
TI  - Investigation into the safety of perineural application of 1,4-butanediol
      diglycidyl ether-crosslinked hyaluronan in a rat model.
AB  - Hyaluronan (HA) is well known for its biocompatibility and has widespread
      clinical use. To change its mechanical and physiologic properties to adapt to
      specific clinical scenarios, HA is crosslinked with chemically reactive linker
      molecules, most of which are toxic chemical reagents. Adverse events related to
      clinical use of crosslinked HA have been documented. Although approved by the FDA
      as dermal filler, the safety of perineural application of 1,4-butanediol
      diglycidyl ether (BDDE)-crosslinked HA has not been assessed critically. Concern
      exists owing to the vulnerability of neural tissues, because of their elongated
      morphology, high ratio of membrane surface area to cell volume, and complicated
      electrophysiologic properties. In this study, we systematically investigated the
      toxicity profile of BDDE-crosslinked HA, using in vitro and in vivo experiments
      in a rat model. The in vivo experiments included the evaluation of aspects of
      histopathology, electrophysiology, and neurobehavior. There were no significant
      changes in the treatment group compared with the control group in all aspects of
      the experiments, except for the increased epineurial vascular formation in the
      0.5% crosslinked HA-treated group during 2 weeks of observation. Further studies
      involving perineural application of BDDE-crosslinked HA can be done based on our
      findings, which ruled out the safety concern of cytotoxicity and adverse changes
      in electrophysiology and neurobehavior.

PMID- 25070221
TI  - Risk factors for polyuria in a cross-section of community psychiatric lithium
      treated patients.
AB  - OBJECTIVES: Polyuria increases the risk of dehydration and lithium toxicity in
      lithium-treated patients. Risk factors have been inconsistently described and the
      variance of this adverse effect remains poorly understood. This study aimed to
      establish independent risk factors for polyuria in a community, secondary-level
      lithium-treated sample of patients. METHODS: This was a cross-sectional study of
      the lithium-treated patients attending a general adult and an old age psychiatry
      service. Participants completed a 24-hour urine collection. Urine volume and the
      presence of polyuria were the outcomes of interest. The relationship between
      outcome and the participant's demographic and clinical characteristics was
      explored with univariable and multivariable analysis. RESULTS: A total of 122
      participants were included in the analysis, with 38% being diagnosed with
      polyuria. Female gender and increased body weight independently predicted the
      presence of polyuria (standardized regression coefficient 1.01 and 0.94,
      respectively; p = 0.002 and p = 0.003, respectively). Female gender and increased
      body weight, lithium dose, and duration of lithium treatment independently
      predicted higher 24-hour urine volumes (standardized regression coefficients
      0.693, p < 0.0005; 0.791, p < 0.0005; 0.276, p = 0.043; 0.181, p = 0.034,
      respectively). Of three different weight metrics, lean body weight was the most
      predictive. CONCLUSIONS: Female gender and increased body weight explain part of
      the variance of this adverse effect. Both risk factors offer fresh insights into
      the pathophysiology of this potentially reversible and dangerous adverse effect
      of lithium treatment. Future research should focus on understanding the
      differences between the genders and between different body compositions in terms
      of lithium pharmacokinetics and pharmacodynamics.

PMID- 25070222
TI  - Field investigation of the quality of fresh and aged leachates from selected
      landfills receiving e-waste in an arid climate.
AB  - The management of electronic waste (e-waste) is a serious problem worldwide and
      much of it is landfilled. A survey of four selected landfills in an arid region
      of South Australia was conducted to determine the proportion of e-waste in
      municipal waste and the properties of each landfill site. Leachate and
      groundwater samples were collected upgradient and downgradient of the landfills
      for analysis of polybrominated diphenyl ethers (PBDEs) and 14 metals and
      metalloids, including Al, As, Ba, Be, Cd, Co, Cr, Cu, Fe, Ni, Pb, Sb, V and Zn.
      Our data demonstrate that the selected landfills in South Australia continue to
      receive municipal waste containing in excess of 6%, or 25,000 tonnes per year, of
      e-waste. The leachates and groundwater collected from the landfills contained
      significantly elevated concentrations of Pb with the highest concentration in
      groundwater of 38 MUg/l, almost four times higher than the Australian drinking
      water guideline of 10 MUg/l. The presence of PBDEs was detected in both leachate
      and groundwater samples. Total PBDEs values of 2.13-59.75 ng/l in leachate
      samples were 10 times higher than in groundwater samples, which recorded a range
      of 0.41-6.53 ng/l at all sites. Moreover, the concentrations of metals and
      metalloids in sampled groundwater contained elevated levels of Al, As, Fe, Ni and
      Pb that exceeded Australian drinking water guideline values. For these reasons
      potential leaching of these contaminants is of concern and while difficult to
      attribute elevated contaminant levels to e-waste, we do not recommend continued
      disposal of e-waste in old landfills that were not originally designed to contain
      leachates. The survey also revealed temporal variation in the electrical
      conductivity and concentrations of As, Cd and Pb present in leachates of
      landfills in arid Mediterranean climates. These results are consistent with the
      marked variations in rainfall patterns observed for such climates. The solute
      concentration (EC and other ions including As, Cd and Pb) declines in the
      leachates during wet winter months (June to September), in contrast to tropical
      countries where such changes are observed during wet summer months.

PMID- 25070223
TI  - Should we routinely stent after ureteropyeloscopy?
AB  - Arguments 'for' and 'against' ureteric stenting after ureteropyeloscopy are
      discussed. An individualised approach balancing renal function preservation,
      irritative lower urinary tract symptoms and emergent return to theatre needs to
      be adopted while being mindful of healthcare spending. 

PMID- 25070225
TI  - Metastatic gastric signet ring cell carcinoma clinically mimicking radiation
      recall dermatitis.

PMID- 25070224
TI  - Facile synthesis of 5H-benzo[b]carbazol-6-yl ketones via sequential reaction of
      Cu-catalyzed Friedel-Crafts alkylation, iodine-promoted cyclization, nucleophilic
      substitution and aromatization.
AB  - A convenient method to access 5H-benzo[b]carbazol-6-yl ketones via a sequential
      Cu-catalyzed Friedel-Crafts alkylation reaction of indoles with 2-(2
      (alkynyl)benzylidene)malonates and iodine-promoted electrophilic cyclization
      followed by nucleophilic substitution and aromatization was developed. The
      products of the functional 5H-benzo[b]carbazol-6-yl ketones were obtained with up
      to 98% yield. 

PMID- 25070226
TI  - Electronically tunable anion-pi interactions in pyrylium complexes: experimental
      and theoretical studies.
AB  - Noncovalent interactions of anions with electron-deficient aromatic rings that
      have been studied so far involve non-heteroaromatic or nitrogen-based
      heteroaromatic systems. Here we report the first case of an organic oxygenated
      aromatic system, in particular the tri-aryl-pyrylium tetrafluoroborate system,
      for which noncovalent anion-pi interactions of the pyrylium cation with the
      tetrafluoroborate anion have been experimentally detected and demonstrated by
      means of (19)F NMR spectroscopy in solution. A series of pyrylium
      tetrafluoroborate salts were synthesized in the presence of BF3.Et2O, by direct
      reaction of 4-substituted benzaldehydes with 4-substituted acetophenones or via
      the previously obtained chalcone of the less reactive ketone. Correlations of
      (19)F NMR chemical shifts of tetrafluoroborate anion for most of the synthesized
      tri-arylpyrylium tetrafluoroborate complexes with both the pyrylium cation
      molecular weight and the standard substituent Hammett constants, demonstrate
      anion-pi(+) interaction to act between the polyatomic anion BF4(-) and the
      pyrylium aromatic system. DFT calculations reveal that an additional (C-H)(+)
      anion hydrogen bond involving the H(5) of pyrylium ring exists for these
      fluorescent dyes that show a tunable cup-to-cap shape cavity. The strong
      fluorescence emission observed for some representative pyrylium
      tetrafluoroborates described herein, makes them a promising class of tunable
      emission wavelength dyes for laser technology applications. 

PMID- 25070227
TI  - Mechanisms of cyst formation after radiosurgery for intracranial arteriovenous
      malformations.

PMID- 25070228
TI  - Principles of musculoskeletal biopsy.
AB  - The appropriate treatment of any musculoskeletal tumor is based on a correct
      diagnosis. In some instances, a patient's history and imaging studies provide
      sufficient information to guide definitive treatment. However, in many cases, a
      biopsy may be necessary. A biopsy, although technically simple, must be conducted
      in a thoughtful manner in order to obtain an accurate tissue sample while
      avoiding complications. Some potential complications include inaccurate sampling,
      improperly placed incision that complicates future surgeries, and healthy tissue
      contamination that can add morbidity to the definitive surgery or preclude the
      chance of limb salvage. This chapter will review the considerations for planning
      and performing a biopsy of musculoskeletal tumors. 

PMID- 25070229
TI  - Imaging evaluation of musculoskeletal tumors.
AB  - In this chapter, we review different imaging modalities, including radiography,
      computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and
      nuclear medicine scintigraphy, and their application to musculoskeletal neoplasm.
      Advantages and limitations of each modality are reviewed, and suggestions for
      imaging approach are provided. 

PMID- 25070230
TI  - Benign bone tumors.
AB  - Benign bone lesions are a broad category that demonstrates a spectrum of
      activities from latent to aggressive. Differentiating the various tumors is
      important in order to properly determine necessary intervention. This chapter
      focuses on the presentation, imaging, diagnostic features, and treatment of the
      most common benign bone tumors in order to help guide diagnosis and management. 

PMID- 25070231
TI  - Osteosarcoma.
AB  - Osteosarcoma is a malignant tumor that primarily affects the long bones but can
      also involve other bones in the body.  It has a bimodal distribution with peaks
      in the second decade of life and late adulthood.  This chapter will highlight the
      clinical presentation, diagnosis, and treatment of osteosarcoma. 

PMID- 25070232
TI  - Ewing's sarcoma of bone.
AB  - Ewing's sarcoma of bone is a primary bone sarcoma found predominantly in patients
      during their second decade of life. It is a high-grade aggressive small round
      blue cell tumor that is part of the Ewing's family of tumors. Its exact eitiology
      is unknown but it commonly demonstrates reproducible staining of CD99 and
      translocations of the EWS gene. Historically, this diagnosis was associated with
      near certain metastasis and subsequent mortality. However, current management
      consists of extensive chemotherapy in addition to local control with surgical
      resection and/or radiation. As a result, survival has improved to the 55-75%
      range in those patients who present without known metastases. Current research
      aims to continue this improvement by looking further into the associated gene
      abnormalities and possibly targeted therapies.

PMID- 25070233
TI  - Chondrosarcoma of bone.
AB  - Chondrosarcoma is a cartilage forming neoplasm, which is the second most common
      primary malignancy of bone. Clinicians who treat chondrosarcoma patients must
      determine the grade of the tumor, and must ascertain the likelihood of
      metastasis. Acral lesions are unlikely to metastasize, regardless of grade,
      whereas axial, or more proximal lesions are much more likely to metastasize than
      tumors found in the distal extremities with equivalent histology. Chondrosarcoma
      is resistant to both chemotherapy and radiation, making wide local excision the
      only treatment. Local recurrence is frequently seen after intralesional excision,
      thus wide local excision is sometimes employed despite significant morbidity,
      even in low-grade lesions. Chondrosarcoma is difficult to treat. The surgeon must
      balance the risk of significant morbidity with the ability to minimize the chance
      of local recurrence and maximize the likelihood of long-term survival. 

PMID- 25070234
TI  - Evaluation and treatment of spinal metastatic disease.
AB  - With the increased survival of oncologic patients, evaluation and management of
      patients with spinal metastasis is crucial to reducing morbidity and maximizing
      function. In this chapter, we present some guidelines for the initial systematic
      evaluation of patients with spinal lesions, as well as the risks, benefits, and
      alternatives to nonoperative and operative management of metastatic spinal
      disease, and the overall survival of these patients. 

PMID- 25070235
TI  - Evaluation and treatment of extremity metastatic disease.
AB  - Metastases can occur as part of the natural progression of a variety of
      malignancies and their mode of spread, manner of presentation, and prognosis are
      as variable as their primary sources. The ultimate goal of musculoskeletal
      treatment of skeletal metastases is to get the patient in question back to his or
      her previous level of function as soon as possible. Skeletal metastases are
      seldom life threatening and their treatment will rarely render someone cured of
      their primary disease. Nevertheless, involvement of a musculoskeletal specialist
      as a part of the multidisciplinary approach can and very often does provide
      significant improvement in patients' qualities of life. The purpose of this
      chapter is to discuss the evaluation of a patient with suspected metastatic
      disease involving the musculoskeletal system and their pre-, intra-, and post
      surgical management as part of a multidisciplinary team. 

PMID- 25070236
TI  - Clinical evaluation and management of benign soft tissue tumors of the
      extremities.
AB  - Benign lesions comprise a majority of soft tissue tumors. It has been estimated
      that their incidence outnumbers that of malignant tumors by a factor of at least
      100 [1]. While history and physical examination can start the diagnostic process,
      imaging including the use of magnetic resonance imaging can be more helpful.
      Biopsy of these tumors is sometimes necessary and can be performed in a number of
      ways, often in conjunction with definitive treatment. Specific diagnostic and
      treatment strategies for a number of the more commonly encountered benign soft
      tissue tumors including lipomas, pigmented villonodular synovitis and hemangiomas
      are reviewed. An algorithm for the management of benign soft tissue tumors is
      discussed.

PMID- 25070237
TI  - Soft tissue sarcomas.
AB  - Sarcoma is a cancer that arises from cells of mesenchymal origin, such as bone,
      cartilage, muscle, fat, vascular, or hematopoietic tissue. It is a very rare form
      of cancer with over 50 histologic subtypes. This chapter discusses selected
      individual subtypes of sarcomas and characteristics specific to each one. It will
      broadly go over molecular biology, etiology, risk factors, and the clinical
      features of this disease. It discusses diagnostic evaluation and the principles
      of management including imaging, biopsy, staging, treatment, follow-up, and the
      importance of a multidisciplinary approach. 

PMID- 25070238
TI  - Functional characterization of platelets in patients with arterial erectile
      dysfunction.
AB  - Arterial erectile dysfunction (ED) is commonly associated with classic
      cardiovascular and metabolic risk factors, such as smoking, hypertension,
      diabetes mellitus, dyslipidaemia and obesity. However, some patients with
      arterial ED do not present any cardiovascular risk factor. As mean platelet
      volume (MPV) has been shown to be directly related to the cardiovascular risk and
      the percentage of platelets expressing the vitronectin receptor (alphaVbeta3),
      involved in the early stages of platelet adhesion, is higher in patients with ED,
      the present study was undertaken to evaluate MPV and alphaVbeta3 in 15 patients
      with arterial ED not associated with any cardiovascular risk factor. Their MPV
      and alphaVbeta3 values were compared with those of men with normal penile
      haemodynamic. Patients with arterial ED had a mean value of MPV (11.25 vs. 9.88
      fL; p < 0.001) and a percentage of platelets expressing the alphaVbeta3 (7.39 vs.
      2.07%; p < 0.001) significantly higher compared to controls. A negative
      correlation was observed between peak systolic velocity and MPV (r = 0.916; p <
      0.001) or alphaVbeta3 (r = 0.930; p < 0.001), whereas MPV and alphaVbeta3
      correlated positively (r = 0.908; p < 0.001). In conclusion, this study showed
      for the first time that MPV and the percentage of platelet expressing alphaVbeta3
      are significantly higher in patients with arterial ED compared to controls. We
      speculate that these parameters of platelet function may be envisaged as markers
      of cardiovascular risk in patients with arterial ED.

PMID- 25070239
TI  - The potential role of GLUT4 transporters and insulin receptors in the
      hypoglycaemic activity of Ficus lutea acetone leaf extract.
AB  - BACKGROUND: Some Ficus species have been used in traditional African medicine in
      the treatment of diabetes. The antidiabetic potential of certain species has been
      confirmed in vivo but the mechanism of activity remains uncertain. The aim was to
      investigate the hypoglycaemic potential of ten Ficus species focussing on glucose
      uptake, insulin secretion and the possible mechanism of hypoglycaemic activity.
      METHODS: The dried and ground leaves of ten Ficus species were extracted with
      acetone. The dried acetone extract was reconstituted with DMSO to a concentration
      of 100 mg/ml which was then serially diluted and used to assay for glucose uptake
      in muscle, fat and liver cells, and insulin secretion in pancreatic cells.
      RESULTS: Only the F. lutea extract was able to modulate glucose metabolism. In
      comparison to insulin in the primary muscle cells, the glucose uptake ability of
      the extract was 33% as effective. In the hepatoma cell line, the extract was as
      effective as metformin in decreasing extracellular glucose concentration by
      approximately 20%. In the pancreatic insulin secretory assay, the extract was 4
      times greater in its secretory activity than commercial glibenclamide. With F.
      lutea extract significantly increasing glucose uptake in the primary muscle
      cells, primary fat cells, C2C12 muscle and H-4-II-E liver cells, the extract may
      act by increasing the activity of cell surface glucose transporters. When the 3T3
      L1 pre-adipocytes were compared to the primary muscle, primary fat and C2C12
      cells, the differences in the former's ability to transport glucose into the cell
      may be due to the absence of the GLUT4 transporter, which on activation via the
      insulin receptor decreases extracellular glucose concentrations. Because the pre
      adipocytes failed to show any active increase in glucose uptake, the present
      effect has to be linked to the absence of the GLUT4 transporter. CONCLUSION: Only
      F. lutea possessed substantial in vitro activity related to glucose metabolism.
      Based on the effect produced in the various cell types, F. lutea also appears to
      be a partial agonist/antagonist of the insulin cell membrane receptor. While the
      clinical effectiveness of F. lutea is not known, this plant species does possess
      the ability to modify glucose metabolism.

PMID- 25070240
TI  - ISL-1 is overexpressed in non-Hodgkin lymphoma and promotes lymphoma cell
      proliferation by forming a p-STAT3/p-c-Jun/ISL-1 complex.
AB  - BACKGROUND: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain
      transcription factor, is essential for the heart, motor neuron and pancreas
      development. Recently, ISL-1 has been found in some types of human cancers.
      However, how ISL-1 exerts the role in tumor development is not clear. METHODS AND
      RESULTS: The expression of ISL-1 was assessed in 211 human lymphoma samples and
      23 normal lymph node samples. Immunohistochemistry results demonstrated a
      markedly higher expression of ISL-1 in 75% of non-Hodgkin lymphoma (NHL) samples
      compared with that in normal lymph nodes or Hodgkin lymphoma (HL) samples. CCK-8
      analysis, cell cycle assay and xenograft model were performed to characterize the
      association between ISL-1 expression level and biological functions in NHL. The
      results showed that ISL-1 overexpression obviously promoted NHL cells
      proliferation, changed the cell cycle distribution in vitro and significantly
      enhanced xenografted lymphoma development in vivo. Real-time PCR, Western blot,
      luciferase assay and ChIP assay were used to explore the potential regulatory
      targets of ISL-1 and the results demonstrated that ISL-1 activated the c-Myc
      expression in NHL by direct binding to a conserved binding site on the c-Myc
      enhancer. Further results revealed that ISL-1 could be positively regulated by
      the c-Jun N-terminal kinase (JNK) and the Janus kinase/signal transducer and
      activator of transcription (JAK/STAT) pathways. Both the JNK and JAK/STAT
      signaling inhibitors could significantly suppressed the growth of NHL cells
      through the down-regulation of ISL-1 as demonstrated by CCK-8 and Western blot
      assays. Bioinformatic analysis and luciferase assay exhibited that ISL-1 was a
      novel target of p-STAT3 and p-c-jun. ChIP, Co-IP and ChIP-re-IP analysis revealed
      that ISL-1 could participate with p-STAT3 and p-c-Jun to form a p-STAT3/p-c
      Jun/ISL-1 transcriptional complex that binds directly on the ISL-1 promoter,
      demonstrating a positive feedback regulatory mechanism for ISL-1 expression in
      NHL. CONCLUSIONS: Our results provide the first evidence that ISL-1 is tightly
      linked to NHL proliferation and development by promoting c-Myc transcription, and
      its aberrant expression was regulated by p-STAT3/p-c-Jun/ISL-1 complex
      activation.

PMID- 25070243
TI  - Cytotoxic effects of pyrrolidine dithiocarbamate in small-cell lung cancer cells,
      alone and in combination with cisplatin.
AB  - The cytocidal effect of pyrrolidine dithiocarbamate (PDTC) was investigated by
      focusing on cell viability, cell cycle arrest and apoptosis induction in small
      cell lung cancer (SCLC) cell lines (NCI-H196 and NCI-H889). PDTC exhibited a much
      stronger dose-dependent cytotoxic activity against NCI-H196 compared to NCI-H889,
      while no such activity was observed in normal human embryonal lung fibroblast MRC
      5 cells. Cell cycle arrest in S phase paralleled with suppression of c-myc
      expression without accompanying DNA fragmentation was observed in NCI-H196 cells.
      A transient increase in the intracellular ROS accompanied with an alteration of
      expression of oxidative stress-related genes was also confirmed in NCI-H196
      cells. Furthermore, the addition of N-acetyl-l-cysteine (NAC), a free radical
      scavenger, not only abolished PDTC-trigger alterations of expression of these
      oxidative-related genes, but also almost completely abrogated PDTC-induced
      reduction in cell viability and morphological changes associated with cell
      damage. These results thus suggest that PDTC-induced cytotoxicity is attributed
      to its pro-oxidant activity. PDTC-induced cytotoxicity was further enhanced by
      CuCl2, however, abolished by bathocuproine disulfonate (BCPS), a non-permeable
      copper-specific chelator, supporting the plausibility that accumulation of
      intracellular Cu plays an important role in the cytotoxicity. Importantly, we
      demonstrated for the first time that PDTC downregulated the expression of ATP7A,
      known to be responsible for Cu efflux, but did not affect the expression of CTR1,
      known as a copper uptake transporter. Intriguingly, combination of much lower
      dose of cisplatin (5 uM) and non-toxic dose of PDTC (0.1 uM) synergistically
      induced a significant cytotoxicity in NCI-H196 cells. Given that ATP7A plays a
      critical role in the resistance of platinum-drug (such as cisplatin) representing
      a first-line treatment for SCLC, PDTC could be a promising candidate of adjunct
      therapeutic reagent for the patients requiring treatment with platinum-based
      regimens. 

PMID- 25070242
TI  - Regulatory T cells and T-cell-derived IL-10 interfere with effective anti
      cytomegalovirus immune response.
AB  - Cytomegalovirus (CMV) establishes lifelong chronic infection in its host with
      mostly asymptomatic or only mild disease, but under immunosuppressive conditions
      the virus can reactivate and infection can cause life-threatening disease. CMV
      has evolved several mechanisms to escape from host's immunity, allowing
      persistence of the virus. Until now, it remains elusive whether regulatory T
      cells (Tregs) have an impact on insufficient host immune response against the
      virus in this context. In the present study, we provide evidence that
      CD4(+)Foxp3(+) naturally occurring Tregs (nTregs) as well as CD4(+)Foxp3(-)IL
      10(+)-induced Tregs (iTregs) interfere with an effective anti-mouse CMV (mCMV)
      immune response. Depletion of Foxp3(+) Tregs by using DEREG mice resulted in
      enhanced T-cell activation as measured by the expression of CD62L, granzyme B and
      interferon (IFN)-gamma and was associated with reduced viral titers in salivary
      glands, the organ where mCMV mainly persists. Moreover, we identified
      CD4(+)Foxp3(-) T cells to produce elevated levels of the immunosuppressive
      cytokine IL-10 at early time points during mCMV infection. Analysis of T-cell
      activation and viral replication in mCMV-infected IL-10(flox/flox) * CD4-cre mice
      and IL-10(flox/flox) * FIC mice revealed that T-cell-specific inactivation of IL
      10, but not Foxp3(+) Treg-specific IL-10 ablation alone, resulted in elevated IFN
      gamma production by T cells associated with a significant decrease in viral loads
      in salivary glands. Thus, our data illustrate a crucial role for CD4(+)Foxp3(+)
      nTregs as well as IL-10-producing CD4(+)Foxp3(-) iTregs in the regulation of
      appropriate T-cell responses and viral clearance during mCMV infection. 

PMID- 25070244
TI  - Langerhans cells promote early germinal center formation in response to
      Leishmania-derived cutaneous antigens.
AB  - Efficient formation of early GCs depends on the close interaction between GC B
      cells and antigen-primed CD4(+) follicular helper T cells (TFH ). A tight and
      stable formation of TFH /B cell conjugates is required for cytokine-driven
      immunoglobulin class switching and somatic hypermutation of GC B cells. Recently,
      it has been shown that the formation of TFH /B cell conjugates is crucial for B
      cell differentiation and class switch following infection with Leishmania major
      parasites. However, the subtype of DCs responsible for TFH -cell priming against
      dermal antigens is thus far unknown. Utilizing a transgenic C57BL/6 mouse model
      designed to trigger the ablation of Langerin(+) DC subsets in vivo, we show that
      the functionality of TFH /B cell conjugates is disturbed after depletion of
      Langerhans cells (LCs): LC-depleted mice show a reduction in somatic
      hypermutation in B cells isolated from TFH /B cell conjugates and markedly
      reduced GC reactions within skin-draining lymph nodes. In conclusion, this study
      reveals an indispensable role for LCs in promoting GC B-cell differentiation
      following cutaneous infection with Leishmania major parasites. We propose that
      LCs are key regulators of GC formation and therefore have broader implications
      for the development of allergies and autoimmunity as well as for future
      vaccination strategies. 

PMID- 25070245
TI  - Alpha1-antitrypsin PiMZ heterozygosity has an independent aggravating effect on
      liver fibrosis in alcoholic liver disease.
AB  - Heterozygous alpha1-antitrypsin deficiency type PiZ (PiMZ) results in chronic
      liver injury and predisposes to hepatocellular carcinoma. Gene frequency of the
      PiZ allele ranges from 0.005 to 0.027 in Western and Central Europe; therefore,
      there is a substantial risk of coincidence with chronic alcohol abuse. This
      retrospective case-control study evaluates the impact of PiMZ genotype on the
      development of chronic liver disease in alcohol consuming patients. Six thousand
      eight hundred eighty-six consecutive liver specimens were immunohistochemically
      tested for PiZ-deposits. From 254 PiZ-positive patients, the liver biopsies of 30
      PiMZ adults without concomitant liver disease other than alcoholic liver disease
      (ALD) were selected and matched to PiMM (wild type) patients with respect to age,
      gender and lifetime daily alcohol ingestion (LDAI). Histomorphological changes
      were assessed using the SAF score and by digital image analysis. Liver cirrhosis
      was significantly more frequent in PIMZ patients than in matched PiMM patients
      (PiMM 9/30 vs. PiMZ 14/30, p = 0.04). Comparison of the extent of fibrosis in
      PiMZ and PiMM livers by two-way ANOVA indicated that the amount of LDAI has a
      major effect in PiMZ and PiMM patients (30.04 % of total variation, p < 0.0001),
      whereas PIMZ genotype has a minor but independent effect on liver fibrosis as
      assessed by digital planimetric evaluation (9.27 % of total variation, p =
      0.005). Semiquantitative assessment was in agreement with this finding.
      Histomorphological findings support that PiMZ heterozygosity has an independent
      aggravating effect on liver fibrosis, even though the pathogenic effect of
      alcohol consumption is much stronger.

PMID- 25070246
TI  - Analysis of stranded information using an automated procedure for strand specific
      RNA sequencing.
AB  - BACKGROUND: Strand specific RNA sequencing is rapidly replacing conventional cDNA
      sequencing as an approach for assessing information about the transcriptome.
      Alongside improved laboratory protocols the development of bioinformatical tools
      is steadily progressing. In the current procedure the Illumina TruSeq library
      preparation kit is used, along with additional reagents, to make stranded
      libraries in an automated fashion which are then sequenced on Illumina HiSeq
      2000. By the use of freely available bioinformatical tools we show, through
      quality metrics, that the protocol is robust and reproducible. We further
      highlight the practicality of strand specific libraries by comparing expression
      of strand specific libraries to non-stranded libraries, by looking at known
      antisense transcription of pseudogenes and by identifying novel transcription.
      Furthermore, two ribosomal depletion kits, RiboMinus and RiboZero, are compared
      and two sequence aligners, Tophat2 and STAR, are also compared. RESULTS: The, non
      stranded, Illumina TruSeq kit can be adapted to generate strand specific
      libraries and can be used to access detailed information on the transcriptome.
      The RiboZero kit is very effective in removing ribosomal RNA from total RNA and
      the STAR aligner produces high mapping yield in a short time. Strand specific
      data gives more detailed and correct results than does non-stranded data as we
      show when estimating expression values and in assembling transcripts. Even well
      annotated genomes need improvements and corrections which can be achieved using
      strand specific data. CONCLUSIONS: Researchers in the field should strive to use
      strand specific data; it allows for more confidence in the data analysis and is
      less likely to lead to false conclusions. If faced with analysing non-stranded
      data, researchers should be well aware of the caveats of that approach.

PMID- 25070247
TI  - Corneal back surface radius after DSEK and DSAEK: a comparative single surgeon
      case control study.
AB  - The purpose of this study was to analyse and compare the visual and refractive
      results after DSEK with manual donor dissection and DSAEK with microkeratome
      assisted donor dissection in a retrospective unmasked case control study. DSEK
      was performed in 15 eyes of 15 patients (74.9 +/- 7.9 years; 4?, 11?). DSAEK was
      performed in 15 eyes of 15 patients (76.5 +/- 6.6 years; 4?, 11?) using the
      Carriazo-Pendular-microkeratome and Schwindt artificial anterior chamber. The
      best corrected visual acuity (BCVA), corneal geometry assessed using Scheimpflug
      photography (SP) and anterior segment optical coherence tomography (AS-OCT) was
      regularly measured in 15 matched pairs receiving DSEK or DSAEK. Mean BCVA
      improved from 1.1 +/- 0.5 to 0.5 +/- 0.2 logMAR (p = 0.001) after DSEK and from
      1.0 +/- 0.5 to 0.2 +/- 0.2 logMAR (p = 0.001) in the DSAEK-group. After 6 months,
      BCVA was significantly better in the DSAEK-group. Corneal refractive power
      decreased from 36.9 +/- 1.5 to 35.9 +/- 1.3 D (p = 0.01) in the DSEK-group and
      from 37.7 +/- 1.6 to 36.4 +/- 1.6 D (p = 0.01) in the DSAEK-group. The corneal
      back surface radius changed from 6.05 +/- 1.6 to 5.82 +/- 0.45 in the DSEK (p =
      0.03) and from 6.72 +/- 0.96 to 5.39 +/- 0.33 in the DSAEK-group (p = 0.01). Mean
      central corneal thickness (CCT) measured by SP decreased from 741 +/- 105 to 605
      +/- 63 um (p = 0.26) after DSEK and from 700 +/- 98 to 607 +/- 88 um (p = 0.01)
      after DSAEK. At no point in time during follow-up, mean CCT was significantly
      different in both groups. The ratio between central and peripheral transplant
      thickness decreased slightly from 0.65 +/- 0.16 to 0.59 +/- 0.16 after DSEK (p =
      0.57) and from 0.52 +/- 0.08 to 0.43 +/- 0.14 after DSAEK (p = 0.17). The ratio
      difference between DSEK and DSAEK-groups was not statistically significant. The
      use of a pendular microkeratome for DSAEK results in faster visual rehabilitation
      but does not decrease the surgically induced change of cornea-based
      hyperopisation which is due to posterior corneal curvature.

PMID- 25070248
TI  - Icosahedral AlCuFe quasicrystal at high pressure and temperature and its
      implications for the stability of icosahedrite.
AB  - The first natural-occurring quasicrystal, icosahedrite, was recently discovered
      in the Khatyrka meteorite, a new CV3 carbonaceous chondrite. Its finding raised
      fundamental questions regarding the effects of pressure and temperature on the
      kinetic and thermodynamic stability of the quasicrystal structure relative to
      possible isochemical crystalline or amorphous phases. Although several studies
      showed the stability at ambient temperature of synthetic icosahedral AlCuFe up to
      ~35 GPa, the simultaneous effect of temperature and pressure relevant for the
      formation of icosahedrite has been never investigated so far. Here we present in
      situ synchrotron X-ray diffraction experiments on synthetic icosahedral AlCuFe
      using multianvil device to explore possible temperature-induced phase
      transformations at pressures of 5 GPa and temperature up to 1773 K. Results show
      the structural stability of i-AlCuFe phase with a negligible effect of pressure
      on the volumetric thermal expansion properties. In addition, the structural
      analysis of the recovered sample excludes the transformation of AlCuFe
      quasicrystalline phase to possible approximant phases, which is in contrast with
      previous predictions at ambient pressure. Results from this study extend our
      knowledge on the stability of icosahedral AlCuFe at higher temperature and
      pressure than previously examined, and provide a new constraint on the stability
      of icosahedrite.

PMID- 25070249
TI  - Decision making at the time of ICD generator change: patients' perspectives.

PMID- 25070251
TI  - Saluting the new generation.

PMID- 25070250
TI  - Spreading the word about the unique and valuable role of healthcare risk
      managers.
AB  - Here I am three-quarters through my year as president of ASHRM and I am still
      pinching myself that I am where I am! How has your year been? It has been a tough
      year for everyone in healthcare. With the Affordable Care Act demands on
      healthcare and the public, concerns about funding, quality initiatives, and
      overall potential loss of revenue, it's a wonder we are still in healthcare. But
      would you be doing anything different? I don't think so. I love that I can help
      make a difference by assisting staff with a difficult patient or situation or
      help a patient with a care concern that they are totally frustrated with or
      explain to a fellow risk manager what I would do in the situation they are
      dealing with. Although we feel like we are being pulled into new healthcare
      territories for our insight and recommendations, it is an indication of the value
      we bring to our organizations. We will get through this and there will be more
      challenges, but as risk management professionals, we can help solve problems and
      create value in the upcoming changes in healthcare. 

PMID- 25070252
TI  - Patient safety: this is public health.
AB  - Avoidable patient harm is a major public health concern, and may already have
      surpassed heart disease as the leading cause of death in the United States. While
      the public health community has contributed much to one aspect of patient harm
      prevention, infection control, the tools and techniques of public health have far
      more to offer to the emerging field of patient safety science. Patient safety
      practice has become increasingly professionalized in recent years, but specialist
      degree programs in the field remain scarce. Healthcare organizations should
      consider graduate training in public health as an avenue for investing in the
      professional development of patient safety practitioners, and schools and
      programs of public health should support further research and teaching to support
      patient safety improvement. 

PMID- 25070253
TI  - Electronic health record-related safety concerns: a cross-sectional survey.
AB  - Federal electronic health record (EHR)-related initiatives are leading to rapid
      increases in their adoption. Despite their benefits, EHRs also introduce new
      risks that can lead to serious safety events. We conducted a Web-based survey of
      the American Society for Healthcare Risk Management and the American Health
      Lawyers Association to elicit perceptions regarding the frequency and types of
      EHR-related serious safety events. We received 369 responses. The majority (66%)
      worked for large hospitals and health systems with varying degrees of EHR
      adoption. More than half (53%) of respondents reported at least one EHR-related
      serious safety event in the previous 5 years, and 10% reported more than 20
      events. EHR workflow (63%), user familiarity with the EHR system (63%), and
      integration with existing systems (59%) were most frequently endorsed as
      variables associated with EHR-related serious safety events. Because EHR-related
      safety concerns are underreported, organizations should consider implementing
      robust measures of EHR safety within their institution as a key step for
      mitigating these concerns. 

PMID- 25070254
TI  - Accountable care and integration: a challenge for credentialing and risk
      management.
AB  - Healthcare reform efforts have resulted in expanded creation of integrated
      organizations such as accountable care organizations. These ACOs, however, create
      additional risk management issues for organizations in terms of antitrust
      compliance, fraud and abuse, and medical liability issues. While much has been
      written on the formation of such organizations, the postformation risks have not
      been explored adequately. This article summarizes some of the risk-management
      challenges that ACOs and other integrated organizations may face. 

PMID- 25070255
TI  - Diagnostic error: untapped potential for improving patient safety?
AB  - How many diagnostic errors occur? How often do errors cause harm, and how serious
      is that harm? Do we understand the major causes of diagnostic errors? Really, we
      don't know how to answer these questions! This article seeks to define a
      challenge facing all healthcare risk managers, whose usual methods of identifying
      and analyzing errors have not, and cannot, supply this missing information. What
      should risk managers do about diagnostic error? Our medical literature
      acknowledges the existence of a problem, but offers few practical solutions. This
      article will review some promising theories from the literature regarding how to
      identify and remediate diagnostic errors, and identify some tools and resources
      available to risk managers. 

PMID- 25070256
TI  - Case law update.

PMID- 25070257
TI  - Tacrolimus 0.1% ointment in the treatment of allergic contact dermatitis: a new
      approach.

PMID- 25070258
TI  - Pharmacological treatments in pregnant women with psoriasis in the U.S.A.

PMID- 25070259
TI  - Reduced drug incorporation into DNA and antiapoptosis as the crucial mechanisms
      of resistance in a novel nelarabine-resistant cell line.
AB  - BACKGROUND: Nine-beta-D-arabinofuranosylguanine (ara-G), an active metabolite of
      nelarabine, enters leukemic cells through human Equilibrative Nucleoside
      Transporter 1, and is then phosphorylated to an intracellular active metabolite
      ara-G triphosphate (ara-GTP) by both cytosolic deoxycytidine kinase and
      mitochondrial deoxyguanosine kinase. Ara-GTP is subsequently incorporated into
      DNA, thereby inhibiting DNA synthesis. METHODS: In the present study, we
      developed a novel ara-G-resistant variant (CEM/ara-G) of human T-lymphoblastic
      leukemia cell line CCRF-CEM, and elucidated its mechanism of ara-G resistance.
      The cytotoxicity was measured by using the growth inhibition assay and the
      induction of apoptosis. Intracellular triphosphate concentrations were
      quantitated by using HPLC. DNA synthesis was evaluated by the incorporation of
      tritiated thymidine into DNA. Protein expression levels were determined by using
      Western blotting. RESULTS: CEM/ara-G cells were 70-fold more ara-G-resistant than
      were CEM cells. CEM/ara-G cells were also refractory to ara-G-mediated apoptosis.
      The transcript level of human Equilibrative Nucleoside Transporter 1 was lowered,
      and the protein levels of deoxycytidine kinase and deoxyguanosine kinase were
      decreased in CEM/ara-G cells. The subsequent production of intracellular ara-GTP
      (21.3 pmol/107 cells) was one-fourth that of CEM cells (83.9 pmol/107 cells)
      after incubation for 6 h with 10 MUM ara-G. Upon ara-G treatment, ara-G
      incorporation into nuclear and mitochondrial DNA resulted in the inhibition of
      DNA synthesis of both fractions in CEM cells. However, DNA synthesis was not
      inhibited in CEM/ara-G cells due to reduced ara-G incorporation into DNA.
      Mitochondrial DNA-depleted CEM cells, which were generated by treating CEM cells
      with ethidium bromide, were as sensitive to ara-G as CEM cells. Anti-apoptotic
      Bcl-xL was increased and pro-apoptotic Bax and Bad were reduced in CEM/ara-G
      cells. CONCLUSIONS: An ara-G-resistant CEM variant was successfully established.
      The mechanisms of resistance included reduced drug incorporation into nuclear DNA
      and antiapoptosis.

PMID- 25070260
TI  - Inputs for subject-specific computational fluid dynamics simulation of blood flow
      in the mouse aorta.
AB  - Mouse models are an important way for exploring relationships between blood
      hemodynamics and eventual plaque formation. We have developed a mouse model of
      aortic regurgitation (AR) that produces large changes in plaque burden with
      charges in hemodynamics [Zhou et al., 2010, "Aortic Regurgitation Dramatically
      Alters the Distribution of Atherosclerotic Lesions and Enhances Atherogenesis in
      Mice," Arterioscler. Thromb. Vasc. Biol., 30(6), pp. 1181-1188]. In this paper,
      we explore the amount of detail needed for realistic computational fluid dynamics
      (CFD) calculations in this experimental model. The CFD calculations use inputs
      based on experimental measurements from ultrasound (US), micro computed
      tomography (CT), and both anatomical magnetic resonance imaging (MRI) and phase
      contrast MRI (PC-MRI). The adequacy of five different levels of model complexity
      (a) subject-specific CT data from a single mouse; (b) subject-specific CT
      centerlines with radii from US; (c) same as (b) but with MRI derived centerlines;
      (d) average CT centerlines and averaged vessel radius and branching vessels; and
      (e) same as (d) but with averaged MRI centerlines) is evaluated by demonstrating
      their impact on relative residence time (RRT) outputs. The paper concludes by
      demonstrating the necessity of subject-specific geometry and recommends for
      inputs the use of CT or anatomical MRI for establishing the aortic centerlines, M
      mode US for scaling the aortic diameters, and a combination of PC-MRI and Doppler
      US for estimating the spatial and temporal characteristics of the input wave
      forms. 

PMID- 25070261
TI  - Novel electroforming-free nanoscaffold memristor with very high uniformity,
      tunability, and density.
AB  - A novel device structure is developed, which uses easy-to-grow nano scaffold
      films to localize oxygen vacancies at vertical heterointerfaces. The strategy is
      to design vertical interfaces using two structurally incompatible oxides, which
      are likely to generate a high-concentration oxygen vacancy. Non-linear
      electroresistance at room temperature is demonstrated using these nano scaffold
      devices. The resistance variations exceed two orders of magnitude with very high
      uniformity and tunability. 

PMID- 25070262
TI  - A standardized method for in vivo mouse pancreas imaging and semiquantitative
      beta cell mass measurement by dual isotope SPECT.
AB  - PURPOSE: In order to evaluate future beta cell tracers in vivo, we aimed to
      develop a standardized in vivo method allowing semiquantitative measurement of a
      prospective beta cell tracer within the pancreas. PROCEDURES: 2-[(123)I]Iodo-L
      phenylalanine ([(123)I]IPA) and [Lys(40)([(111)In]DTPA)]exendin-3 ([(111)In]Ex3)
      pancreatic uptake and biodistribution were evaluated using SPECT,
      autoradiography, and an ex vivo biodistribution study in a controlled
      unilaterally nephrectomized mouse beta cell depletion model. Semiquantitative
      measurement of the imaging results was performed using [(123)I]IPA to delineate
      the pancreas and [(111)In]Ex3 as a beta cell tracer. RESULTS: The uptake of
      [(123)I]IPA was highest in the pancreas. Aside from the kidneys, the uptake of
      [(111)In]Ex3 was highest in the pancreas and lungs. Autoradiography showed only
      uptake of [(111)In]Ex3 in insulin-expressing cells. Semiquantitative measurement
      of [(111)In]Ex3 in the SPECT images based on the delineation of the pancreas with
      [(123)I]IPA showed a high correlation with the [(111)In]Ex3 uptake data of the
      pancreas obtained by dissection. A strong positive correlation was observed
      between the relative insulin positive area and the pancreas-to-blood ratios of
      [(111)In]Ex3 uptake as determined by counting with a gamma counter and the
      semiquantitative analysis of the SPECT images. CONCLUSIONS: [(123)I]IPA is a
      promising tracer to delineate pancreatic tissue on SPECT images. It shows a high
      uptake in the pancreas as compared to other abdominal tissues. This study also
      demonstrates the feasibility and accuracy to measure the beta cell mass in vivo
      in an animal model of diabetes.

PMID- 25070263
TI  - High glucose reduces hepatic glycogenesis by suppression of microRNA-152.
AB  - MicroRNAs (miRNAs) are a class of non-coding 18-25-nucleotide endogenous RNA
      molecules. miRNAs act as specific gene silencers to regulate target gene
      expression at the posttranscriptional level, by base pairing to the 3'
      untranslated region of the target mRNA. miR-152 is an miRNA that was originally
      identified in cancer cells, and was shown to be able to modulate the expression
      of specific oncogenes and tumor suppressor genes, leading to enhanced carcinoma
      growth. However, little is known regarding the role of miR-152 in the regulation
      of hepatic insulin resistance and glucose metabolism. In the present study, it
      was identified that the activation of AKT and glycogen synthase kinase 3 (GSK-3),
      and the expression levels of glycogen, were reduced in mouse NCTC 1469
      hepatocytes and mouse primary hepatocytes, following exposure to 25 mM glucose
      for 48 h. Furthermore, it was demonstrated that high glucose levels suppressed
      the expression of miR-152 in hepatocytes. In order to further assess the effects
      of miR-152 on the glucose-induced reduction of glycogen synthesis and activation
      of AKT and GSK, miR-152 mimic and inhibitor were transfected into the NCTC 1469
      cells, respectively. The transfection of the miR-152 inhibitor resulted in
      reduced expression of glycogen, accompanied by impaired phosphorylation of AKT
      and GSK in the NCTC 1469 cells treated with or without glucose. Conversely,
      upregulation of miR-152 by transfection of an miR-152 mimic reversed the glucose
      induced decrease in glycogen synthesis and reduced AKT and GSK phosphorylation in
      hepatocytes. This indicated that miR-152 could modulate the AKT/GSK pathway and
      glycogen synthesis. In conclusion, to the best of our knowledge, this study was
      the first to indicate that high glucose impaired the activation of the AKT/GSK
      pathway and the synthesis of glycogen in mouse hepatocytes, in part through the
      downregulation of miR-152.

PMID- 25070264
TI  - Special issue on Advance Biological Treatment Technologies for Sustainable Waste
      Management: selected papers from "International Conference on Solid Waste-
      Innovation in Technology and Management (ICSWHK2013)", 5-9 May 2013, Hong Kong
      Convention and Exhibition Centre, Hong Kong SAR.

PMID- 25070265
TI  - Updates in biological therapies for knee injuries: anterior cruciate ligament.
AB  - There have been many advances in anterior cruciate ligament reconstruction (ACLR)
      techniques incorporating biological treatment. The aim of this review is to
      discuss the recent contributions that may enlighten our understanding of
      biological therapies for anterior cruciate ligament (ACL) injuries and improve
      management decisions involving these enhancement options. Three main biological
      procedures will be analyzed: bio-enhanced ACL repair, bio-enhanced ACLR
      scrutinized under the four basic principles of tissue engineering (scaffolds,
      cell sources, growth factors/cytokines including platelet-rich plasma, and
      mechanical stimuli), and remnant-preserving ACLR. There is controversial
      information regarding remnant-preserving ACLR, since different procedures are
      grouped under the same designation. A new definition for remnant-preserving ACLR
      surgery is proposed, dividing it into its three major procedures (selective
      bundle augmentation, augmentation, and nonfunctional remnant preservation); also,
      an ACL lesion pattern classification and a treatment algorithm, which will
      hopefully standardize these terms and procedures for future studies, are
      presented. 

PMID- 25070266
TI  - Rapid and sensitive determination of free thiols by capillary zone
      electrophoresis with near-infrared laser-induced fluorescence detection using a
      new BODIPY-based probe as labeling reagent.
AB  - A CZE with near-infrared (NIR) LIF detection method has been developed for the
      analysis of six low molecular weight thiols including glutathione, homocysteine,
      cysteine, gamma-glutamylcysteine, cysteinylglycine, and N-acetylcysteine. For
      this purpose, a new NIR fluorescent probe, 1,7-dimethyl-3,5-distyryl-8-phenyl-(4'
      iodoacetamido)difluoroboradiaza-s-indacene was utilized as the labeling reagent,
      whose excitation wavelength matches the commercially available NIR laser line of
      635 nm. The optimum procedure included a derivatization step of the free thiols
      at 45 degrees C for 25 min and CZE analysis conducted within 14 min in the
      running buffer containing 16 mmol/L pH 7.0 sodium citrate and 60% v/v ACN. The
      LODs (S/N = 3) ranged from 0.11 nmol/L for N-acetylcysteine to 0.31 nmol/L for
      gamma-glutamylcysteine, which are better than or comparable to those reported
      with other derivatization-based CE-LIF methods. As the first trial of NIR CE-LIF
      method for thiol determination, the practical application of the proposed method
      has been validated by detecting thiols in cucumber and tomato samples with
      recoveries of 96.5-104.3%.

PMID- 25070267
TI  - Metabolic responses to lead of metallicolous and nonmetallicolous populations of
      Armeria maritima.
AB  - Metabolic responses to Pb(NO3)2 (Pb) ions of excised leaves of metallicolous
      (MPs) and nonmetallicolous populations (NMPs) of Armeria maritima, cultivated on
      normal soil, were examined. Detached leaves were exposure to Pb for 24 h, and
      metabolic parameters were investigated. Pb decreased the photosynthesis (Pn) rate
      and photosystem II (PSII) activity, whereas the photochemical efficiency of PSII
      remained unchanged. In both populations, Pb ions caused increase in O2 uptake of
      dark-treated leaves; however, respiration after Pn was not affected. Pb increased
      superoxide dismutase activity in MP leaves and malondialdehyde content in NMP
      leaves. Other metabolites after Pb treatment were increased (proline or H2O2) or
      decreased (malate). Ascorbate peroxidase activity and adenosine triphosphate
      content decreased more in MP than in NMP leaves. Our results indicate that A.
      maritima is well adapted to heavy metal-contaminated soils, and we discuss
      potential causes of the stimulation of respiration by Pb ions and possible
      reasons for the tolerance to oxidative stress of plants growing in a metal-rich
      habitat.

PMID- 25070268
TI  - Persistence of endocrine disruption in zebrafish (Danio rerio) after discontinued
      exposure to the androgen 17beta-trenbolone.
AB  - The aim of the present study was to investigate the effects of the androgenic
      endocrine disruptor 17beta-trenbolone on the sexual development of zebrafish
      (Danio rerio) with special emphasis on the question of whether adverse outcomes
      of developmental exposure are reversible or persistent. An exposure scenario
      including a recovery phase was chosen to assess the potential reversibility of
      androgenic effects. Zebrafish were exposed to environmentally relevant
      concentrations of 17beta-trenbolone (1 ng/L-30 ng/L) from fertilization until
      completion of gonad sexual differentiation (60 d posthatch). Thereafter, exposure
      was either followed by 40 d of recovery in clean water or continued until 100 d
      posthatch, the age when zebrafish start being able to reproduce. Fish exposed for
      100 d to 10 ng/L or 30 ng/L 17beta-trenbolone were masculinized at different
      biological effect levels, as evidenced from a concentration-dependent shift of
      the sex ratio toward males as well as a significantly increased maturity of
      testes. Gonad morphological masculinization occurred in parallel with decreased
      vitellogenin concentrations in both sexes. Changes of brain aromatase (cyp19b)
      mRNA expression showed no consistent trend with respect to either exposure
      duration or concentration. Gonad morphological masculinization as well as the
      decrease of vitellogenin persisted after depuration over 40 d in clean water.
      This lack of recovery suggests that androgenic effects on sexual development of
      zebrafish are irreversible.

PMID- 25070269
TI  - Reappraising the relationship between working memory and conscious awareness.
AB  - Classically, the operation of working memory (WM) has been strongly coupled with
      conscious states; it is thought that WM operates on conscious input and that we
      are conscious of the contents and operations of WM. Here, we re-evaluate the
      relationship between WM and conscious awareness in light of current data and
      question the views that awareness is mandatory for the operation of WM and that
      WM contents are necessarily linked to experiential states that are consciously
      accessible for perceptual report. We propose a novel framework for the
      relationship between WM and conscious awareness. 

PMID- 25070270
TI  - An unusual presentation of an intraosseous epidermoid cyst of the anterior
      maxilla: a case report.
AB  - INTRODUCTION: Intraosseous epidermoid inclusion cysts are rare benign epithelial
      inclusion cysts in the bone. They are usually found in the cranium and hand
      phalanges. They are slow growing lesions, and it is difficult to differentiate
      them from other inflammatory and cystic lesions. Only a few cases of epidermoid
      inclusion cyst in the jaw have been reported in the literature. This is the
      fourth case reported as intraosseous epidermoid cyst of the maxilla in the
      English literature. CASE PRESENTATION: An asymptomatic 59-year-old Caucasian man
      was referred to our Oral and Maxillofacial Surgery clinic for a unilocular
      radiolucent area at his anterior maxilla shown on an orthopantomograph. He was
      scheduled for surgery and underwent cyst extraction surgery. A pathological
      examination revealed epidermoid cyst. The diagnostic dilemma in this case report
      in opposition to the presented intraosseous epidermoid cysts in the literature is
      that there was no trauma history to his upper jaw. Treatment for this cyst is
      conservative surgical excision and recurrence is uncommon. CONCLUSIONS: This
      report presents an unusual case of an intraosseous epidermoid cyst that occurred
      with no trauma history to the upper jaw. Although only three cases of epidermoid
      inclusion cyst have been reported in the maxilla, epidermoid inclusion cyst
      should be considered in the differential diagnosis of radiolucent lesions of the
      jaws.

PMID- 25070271
TI  - Efficacy of a behavioral intervention for reducing sedentary behavior in persons
      with multiple sclerosis: a pilot examination.
AB  - BACKGROUND: Sitting time (ST), a form of sedentary behavior, has been identified
      as a highly prevalent risk factor for multiple sclerosis (MS)-related morbidity.
      There is limited information on the efficacy of behavioral interventions for
      reducing ST in persons with MS. PURPOSE: To examine the efficacy of a behavioral
      intervention for reducing ST in persons with MS in a pilot RCT. METHODS: Seventy
      MS patients were randomly assigned to intervention and waitlist control
      conditions. The behavioral intervention was delivered April-September 2012 via
      the Internet and consisted of a dedicated website and one-on-one Skype video
      chats that taught participants the skills, techniques, and strategies for
      reducing sedentary behavior based on social cognitive theory. ST was measured by
      questions on the abbreviated International Physical Activity Questionnaire (IPAQ)
      before and after the 6-month RCT. Data were analyzed in SPSS, version 21.0 in
      March 2014. RESULTS: ANCOVA was performed on post-intervention scores controlling
      for pre-intervention values using an intent-to-treat analysis. The group main
      effect was statistically significant (F[1, 67]=4.03, p<0.05, eta2=0.06) and
      yielded a parameter estimate of 98.9 (SE=49.3, t=2.01, p<0.05). The adjusted mean
      scores for intervention and control groups were 429.2 (201.2) and 528.2 (200.7)
      minutes of ST, respectively (d=0.49). CONCLUSION: We provide the first data on
      the efficacy of a behavioral intervention for reducing ST in MS patients. This
      highlights the importance of designing and testing the effect of behavioral
      interventions that reduce ST on secondary outcomes such as function, symptoms,
      quality of life, and health status in persons with MS.

PMID- 25070272
TI  - Analytical strategies in human growth research.
AB  - Human growth research requires knowledge of longitudinal statistical methods that
      can be analytically challenging. Even the assessment of growth between two ages
      is not as simple as subtracting the first measurement from the second, for
      example. This article provides an overview of the key analytical strategies
      available to human biologists in increasing order of complexity, starting with a
      review on how to express cross-sectional measurements of size, before covering
      growth (conditional regression models, regression with conditional growth
      measures), growth curves (individual growth curves, mixed effects growth curves,
      latent growth curves), and patterns of growth (growth mixture modeling). The
      article is not a statistical treatise and has been written by a human biologist
      for human biologists; as such, it should be accessible to anyone with training in
      at least basic statistics. A summary table linking each analytical strategy to
      its applications is provided to help investigators match their hypotheses and
      measurement schedules to an analysis plan. In addition, worked examples using
      data on non-Hispanic white participants in the Fels Longitudinal Study are used
      to illustrate how the analytical strategies might be applied to gain novel
      insight into human growth and its determinants and consequences. All too often,
      serial measurements are treated as cross-sectional in analyses that do not
      harness the power of longitudinal data. The broad goal of this article is to
      encourage the rigorous application of longitudinal statistical methods to human
      growth research.

PMID- 25070273
TI  - Timing of CMV-specific effector memory T cells predicts viral replication and
      survival after allogeneic hematopoietic stem cell transplantation.
AB  - The aim of this study was to characterize timing, kinetic, and magnitude of CMV
      specific immune response after hematopoietic stem cell transplantation (HSCT) and
      its ability to predict CMV replication and clinical outcomes. Using cell surface
      and intracellular cytokine staining by flow cytometry, CMV-specific T-cell
      response was measured in blood, while CMV viral load and chimerism were
      determined by real-time PCR. Patients that reconstituted CMV-specific T-cell
      response within 6 weeks after Allo-SCT showed a more robust immune response
      (CD8(+) : 0.7 cells/MUl vs. 0.3/MUl; P-value = 0.01), less incidence of CMV
      replication (33% vs. 89.5%; P-value = 0.007), reduced viral loads (1.81 log
      copies/ml vs. 0 copies/ml; P-value = 0.04), and better overall survival (72%; CI:
      0.53-0.96 vs. 42% CI: 0.24-0.71; P-value = 0.07) than patients with a delayed
      immune reconstitution. Viremic patients had significantly higher transplant
      related mortality than nonviremic patients after 1 year (33% CI: 0.15-0.52 vs. 0%
      CI: 0.05-0.34; P-value = 0.01). Risk factors independently associated with viral
      replication were receptor pretransplant CMV-positive serostatus (P-value = 0.02)
      and acquiring CMV-specific T-cell response after 6 weeks post-transplantation (P
      value = 0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell
      immune response after transplantation may identify patients with different risk
      for viral replication and different clinical outcomes, including survival. 

PMID- 25070275
TI  - Classical indications are useful for initiating continuous renal replacement
      therapy in critically ill patients.
AB  - The optimal timing for initiating continuous renal replacement therapy (CRRT)
      remains controversial, and it is not obvious which parameters should be
      considered during this process. We investigated the predictive value of
      physiological parameters among critically ill patients receiving CRRT due to
      acute kidney injury (AKI). A total of 496 patients who started CRRT were
      prospectively enrolled. The following physiological parameters were significantly
      associated with mortality even after multivariate adjustments: level of pH
      [hazard ratio (95% CI): 7.15 < pH <= 7.20, 1.971 (1.319-2.946); pH <= 7.15, 2.315
      (1.586-3.380); reference > 7.25, P-for-trend < 0.001]; bicarbonate level (HCO3(
      )) [<= 14 mmol/L, 2.010 (1.542-2.620); reference > 18 mmol/L, P-for-trend <
      0.001]; phosphorus level [> 7 mmol/L, 1.736 (1.313-2.296); reference <= 5 mmol/L,
      P-for-trend < 0.001]; and urine output < 0.3 ml/kg/hr [1.509 (1.191-1.912);
      reference > 0.3 ml/kg/hour]. Weight gain over 2 kg was associated with mortality
      exclusively according to univariate analysis [1.516 (1.215-1.892)]. The
      diagnostic value of the composite of these factors (pH, bicarbonate level,
      phosphorus level, urine output, weight gain, and potassium levels) [area under
      the curve (AUC) 0.701, 95% CI 0.644-0.759] was comparable to or higher than the
      blood urea nitrogen level (AUC 0.571, 95% CI 0.511-0.630), serum creatinine level
      (AUC 0.462, 95% CI 0.399-0.525), eGFR (AUC 0.541, 95% CI 0.478-0.605), and AKI
      Network stage (AUC 0.627, 95% CI 0.561-0.692). In conclusion, the physiological
      parameters are useful in predicting post-AKI mortality and should be considered
      when initiating CRRT in critically ill patients with AKI. 

PMID- 25070274
TI  - Suspected invasive placenta: evaluation with magnetic resonance imaging.
AB  - PURPOSE: To determine the utility of magnetic resonance imaging (MRI) in
      diagnosing invasive placenta (IP). MATERIALS AND METHODS: MRI findings in 32
      women with suspected IP were evaluated independently by four readers.
      Interobserver agreement was calculated with kappa (kappa) statistics.
      Associations between MRI findings and IP were assessed by univariate and
      multivariate analyses. Sensitivity, specificity and accuracy of MRI for the
      diagnosis of IP were estimated. RESULTS: Sixteen women (16/32; 50%) had confirmed
      IP. Interobserver correlation for the diagnosis of IP was fair (kappa = 0.40).
      Univariate analysis revealed that thinning or focal defect of the uteroplacental
      interface (P < 0.0001) was the most discriminating MRI variable in the
      differentiation between normal and IP. Overall sensitivity and specificity of MRI
      for the diagnosis of IP were 84% [95% CI: 75-94%] and 80% [95% CI: 66-93%],
      respectively. Thinning or focal defect of the uteroplacental interface was the
      most accurate finding (88%) in the diagnosis of IP. Multivariate analysis
      revealed that thinning or focal defect of the uteroplacental interface was the
      single independent predictor of IP (P = 0.0006; OR = 64.99). CONCLUSION: MR
      imaging has 84% sensitivity [95% CI: 75-94%] and 80% specificity [95% CI: 66-93%]
      for the diagnosis of IP. Thinning or focal defect of the uteroplacental interface
      is the most discriminating independent MR variable in differentiating between
      normal placenta and IP. KEY POINTS: MR imaging has acceptable degrees of accuracy
      to diagnose invasive placenta. Focal uteroplacental interface defect is the best
      finding to diagnose invasive placenta. Focal uteroplacental interface defect is
      the single independent predictor of invasive placenta.

PMID- 25070276
TI  - Chiral carbonaceous nanotubes containing twisted carbonaceous nanoribbons,
      prepared by the carbonization of chiral organic self-assemblies.
AB  - Single-handed helical silica nanotubes containing chiral organic self-assemblies
      were prepared by using a supramolecular templating approach. After carbonization
      and the removal of the silica, single-handed helical carbonaceous nanotubes that
      contained twisted carbonaceous nanoribbons were obtained. It is believed that the
      nanotubes formed as a result of the adsorption of low-molecular-weight gelators.
      The twisted nanoribbons were formed because of the carbonization of the organic
      self-assemblies. The samples were characterized by using field-emission scanning
      electron microscopy, transmission electron microscopy, X-ray diffraction, Raman
      spectroscopy, and circular dichroism. For the samples carbonized at 900  degrees
      C for 3.0 h, a partially graphitized structure was identified. The circular
      dichroism (CD) spectra indicated that the twisted nanoribbons exhibited optical
      activity. The CD spectrum was simulated by using time-dependent density
      functional theory. The results suggested that the CD signals originated from the
      chiral stacking of aromatic rings.

PMID- 25070277
TI  - Anti-allodynic effects of obtusifolin and gluco-obtusifolin against inflammatory
      and neuropathic pain.
AB  - Inflammatory pain and neuropathic pain are major health issues that represent
      considerable social and economic burden worldwide. In this study we investigated
      the potential of obtusifolin and gluco-obtusifolin, two anthraquinones found in
      the seeds of the widely used traditional Chinese medical botanical Cassia
      obtusifolia, to reduce neuropathic and inflammatory pain. The potential analgesic
      effects of obtusifolin and gluco-obtusifolin were evaluated by mice formalin test
      and complete Freund's adjuvant (CFA)-induced nociceptive behaviors in rats.
      Chronic constriction injury (CCI), L5 spinal nerve ligation (L5 SNL), diabetes,
      and chemotherapeutics inducing allodynia were used to test whether repeated
      treatment with obtusifolin and gluco-obtusifolin ameliorated neuropathic pain.
      Finally, we explored whether obtusifolin and gluco-obtusifolin altered the degree
      of neuroinflammation in rat spinal cord after CFA administration and CCI
      induction. Obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reduced
      licking/biting time in dose-dependent manner in phase 2 of formalin-induced
      behavior in mice. Furthermore, repeated administration of obtusifolin and gluco
      obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reversed mechanical allodynia induced by
      CFA, CCI, L5 SNL, diabetes, and oxaliplatin in a dose-dependent manner in rats.
      Levels of activated nuclear factor-kappa B (NF-kappaB) and proinflammatory
      cytokines (interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha))
      in lumbar spinal cord were elevated in rats following CFA treatment and CCI
      induction, and obtusifolin and gluco-obtusifolin significantly inhibited these
      effects. Our results demonstrate that obtusifolin and gluco-obtusifolin produce
      significant antinociceptive action in rodent behavioral models of
      inflammatory/neuropathic pain, and that this activity is associated with
      modulation of neuroinflammation in spinal cord.

PMID- 25070278
TI  - Emergence of Panton-Valentine leukocidin-positive ST59 methicillin-susceptible
      Staphylococcus aureus with high cytolytic peptide expression in association with
      community-acquired pediatric osteomyelitis complicated by pulmonary embolism.
AB  - A 15-year-old boy, who had had a furuncle on his femur, developed femoral
      pyomyositis and osteomyelitis complicated by septic pulmonary embolism. Panton
      Valentine leukocidin-positive (PVL(+)) ST59 methicillin-susceptible
      Staphylococcus aureus (MSSA) was isolated from pus and blood. Chemotherapy was
      started with cefazolin, followed by combination therapy with meropenem/vancomycin
      with surgery. The MSSA (strain KS1) was positive for increased levels of
      cytolytic peptide (psmalpha and hld) and staphylococcal enterotoxin B (SEB), and
      manifested IS1216V-mediated multidrug resistance (to erythromycin, clindamycin,
      kanamycin, streptomycin, and chloramphenicol), similar to a genome-analyzed
      reference strain (PM1) of ST59/SCCmecV(5C2&5) community-associated methicillin
      resistant S. aureus (Taiwan CA-MRSA), but unlike another reference strain (M013)
      of Taiwan CA-MRSA in terms of resistance. The data suggest that CA-MSSA KS1,
      characterized by PVL, increased levels of cytolytic peptide, SEB, and multidrug
      resistance, is a possible ancestral strain of Taiwan CA-MRSA and causes the
      unique association of osteomyelitis and septic pulmonary embolism, requiring
      complicated management. 

PMID- 25070279
TI  - Bacteremic pneumonia caused by extended-spectrum beta-lactamase-producing
      Escherichia coli and Klebsiella pneumoniae: Appropriateness of empirical
      treatment matters.
AB  - BACKGROUND: Clinical information about bacteremic pneumonia caused by extended
      spectrum beta-lactamase (ESBL)-producing organism is limited. METHODS: A
      retrospective study was conducted at two medical centers in Taiwan. From May 2002
      to August 2010, clinical information and outcome of adults with bacteremic
      pneumonia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae
      were analyzed. The primary outcome is the 30-day mortality. RESULTS: A total of
      111 patients with bacteremic pneumonia caused by E. coli (37 patients, 33.3%) and
      K. pneumoniae (74, 66.7%) were identified. Their mean age was 69.2 years and
      51.4% were male patients. Fifty-seven (51.3%) episodes were classified as
      hospital-acquired infections, 19 (17.1%) as health-care-associated infections,
      and four (3.6%) as community-acquired infections. Fifty-one (45.9%) patients
      received appropriate empiric antimicrobial therapy. The 30-day mortality rate was
      40.5% (45 patients). In the multivariate analysis, several independent risk
      factors, including rapidly fatal underlying disease [odds ratio (OR), 5.75; 95%
      confidence interval (CI), 1.54-21.48; p = 0.009], severe sepsis (OR, 4.84; 95%
      CI, 1.55-15.14; p = 0.007), critical illness (OR, 4.28; 95% CI, 1.35-13.57; p =
      0.013), and receipt of appropriate empirical therapy (OR, 0.19; 95% CI, 0.07
      0.55; p = 0.002), were associated with 30-day mortality. The survival analysis
      consistently found that individuals with appropriate empiric therapy had a higher
      survival rate (log-rank test, p < 0.001). CONCLUSION: ESBL-producing bacteremic
      pneumonia, especially health-care-associated infections, often occurred in adults
      with comorbidities. Appropriate empirical therapy was associated with a favorable
      outcome.

PMID- 25070280
TI  - Monomicrobial Aeromonas and Vibrio bacteremia in cirrhotic adults in southern
      Taiwan: Similarities and differences.
AB  - BACKGROUND/PURPOSE: Aeromonas and Vibrio are important water-borne pathogens
      causing substantial morbidity and mortality in cirrhotic patients in Taiwan, but
      the differences in clinical manifestations of Aeromonas and Vibrio bacteremia
      have not been reported in detail. METHODS: From January 2003 to September 2013,
      cirrhotic patients with monomicrobial Aeromonas or Vibrio bacteremia at a medical
      center in Taiwan were included in this study. RESULTS: The study population
      consisted of 77 cirrhotic patients with Aeromonas bacteremia and 48 patients with
      Vibrio bacteremia. Both pathogens clustered during the summer season; Vibrio
      bacteremia was more correlated with higher temperatures (Vibrio: r(2) = 0.95, p <
      0.0001; Aeromonas: r(2) = 0.74, p = 0.006) and was associated with ingestion of
      undercooked seafood (p = 0.03) or cutaneous exposure (p < 0.001). Vibrio
      bacteremia mainly occurred in mildly or moderately decompensated cirrhosis (Child
      Pugh class A and B: 45.8% vs. 20.8%, p = 0.003), and caused more soft-tissue
      infections (31.3% vs. 5.2%; p < 0.001) and renal dysfunction (1.6 +/- 1.2 mg/dL
      vs. 1.3 +/- 0.8 mg/dL, p = 0.006). Sepsis-related mortality was similar in the
      cases of Vibrio and Aeromonas bacteremia (14.6% vs. 14.3%, p = 0.96), but those
      with Vibrio bacteremia underwent a fulminant course, as evidenced by a shorter
      time from bacteremia onset to death (3.1 days vs. 8.2 days, p = 0.04).
      CONCLUSION: In cirrhotic patients, bacteremia caused by Aeromonas and Vibrio
      species clustered in summer months and caused similar mortality, but Vibrio
      bacteremia led to a more severe and fulminant sepsis.

PMID- 25070281
TI  - Population-based incidence of community-acquired pneumonia hospitalization in
      Hong Kong children younger than 5 years before universal conjugate pneumococcal
      immunization.
AB  - OBJECTIVES: We sought to document the incidence of pediatric hospitalization for
      bacterial pneumonia before universal childhood conjugate pneumococcal vaccination
      using two different methods of diagnosis. METHODS: By following the World Health
      Organization (WHO) chest radiography (CXR) protocol, two radiologists
      independently read the CXRs of a cohort of systematically recruited children
      younger than 5 years. The children had acute respiratory infections and were
      admitted to one of two hospitals that care for 72.5% of all pediatric admissions
      on Hong Kong Island. Medical records were reviewed for clinical manifestation and
      to identify bacterial pneumonia diagnosed by pediatricians. RESULTS: In children
      younger than 5 years, the incidences of bacterial pneumonia, as diagnosed by
      pediatricians and by the WHO CXR standard, were 775.7 per 100,000 population [95%
      confidence interval (CI, 591.8-998.3)] and 439.5 per 100,000 population (95% CI,
      304.6-614.5), respectively. The study period was from 2002 to 2004. CONCLUSION:
      This study provided a reliable baseline estimate of the hospitalization burden of
      pneumococcal pneumonia in Hong Kong children before the advent of universal
      conjugate pneumococcal vaccination.

PMID- 25070282
TI  - Cholesterol glucosylation by Helicobacter pylori delays internalization and
      arrests phagosome maturation in macrophages.
AB  - BACKGROUND/PURPOSE: Helicobacter pylori colonizes the human stomach and
      contributes to chronic inflammation of the gastric mucosa. H. pylori persistence
      occurs because of insufficient eradication by phagocytic cells. A key factor of
      H. pylori, cholesterol-alpha-glucosyltransferase encoded by capJ that extracts
      host cholesterol and converts it to cholesteryl glucosides, is important to evade
      host immunity. Here, we examined whether phagocytic trafficking in macrophages
      was perturbed by capJ-carrying H. pylori. METHODS: J774A.1 cells were infected
      with H. pylori at a multiplicity of infection of 50. Live-cell imaging and
      confocal microscopic analysis were applied to monitor the phagocytic trafficking
      events. The viability of H. pylori inside macrophages was determined by using
      gentamicin colony-forming unit assay. The phagocytic routes were characterized by
      using trafficking-intervention compounds. RESULTS: Wild type (WT) H. pylori
      exhibited more delayed entry into macrophages and also arrested phagosome
      maturation more than did capJ knockout mutant. Pretreatment of genistein and
      LY294002 prior to H. pylori infection reduced the internalization of WT but not
      capJ-knockout H. pylori in macrophages. CONCLUSION: Cholesterol glucosylation by
      H. pylori interferes with phagosome trafficking via a lipid-raft and PI3K
      dependent manner, which retards engulfment of bacteria for prolonged
      intracellular survival of H. pylori.

PMID- 25070283
TI  - Detection of anti-p155/140, anti-p140, and antiendothelial cells autoantibodies
      in patients with juvenile dermatomyositis.
AB  - BACKGROUND/PURPOSE: The pathogenesis of juvenile dermatomyositis (JDM), the most
      common idiopathic inflammatory myopathy in children, is unclear. The
      identification of novel autoantibodies in JDM may have clinical implications. The
      aim of this study was to assess the presence of anti-p155/140, anti-p140
      antibodies, and antiendothelial cells antibodies (AECA) in patients with JDM and
      to correlate autoantibodies with clinical manifestations. METHODS: Serum AECA
      against human umbilical vein endothelial cells were detected by enzyme-linked
      immunosorbent assay in 25 patients with JDM and 17 normal controls.
      Immunoblotting was performed to detect serum anti-p155/140 and anti-p140
      antibodies. RESULTS: Patients with JDM had significantly higher serum levels of
      AECA than healthy controls (p = 0.002). Nineteen patients (76%) and five control
      patients (29.4%) had positive AECAs (p = 0.003). The cutoff point of serum levels
      of AECA was determined by the receiver operating characteristic (ROC) curve
      analysis. Anti-p155/140 and anti-p140 antibodies were detected in 9 patients and
      7 patients with JDM (36% and 28%, respectively). Anti-p155/140 antibodies were
      significantly associated with higher proportion of ESR elevation (100% vs. 0%, p
      = 0.006), higher erythrocyte sedimentation rate levels at diagnosis (40.3 +/-
      15.5 vs. 13.4 +/- 5.3, p = 0.019), and a younger age at diagnosis (5.2 +/- 3.2
      years vs. 8.0 +/- 3.0 years, p = 0.03). CONCLUSION: anti-p155/140, anti-p140, and
      AECA antibodies are significantly associated with JDM. The roles of
      autoantibodies in the pathogenesis await further investigation.

PMID- 25070284
TI  - In-cell NMR and EPR spectroscopy of biomacromolecules.
AB  - The dream of cell biologists is to be able to watch biological macromolecules
      perform their duties in the intracellular environment of live cells. Ideally, the
      observation of both the location and the conformation of these macromolecules
      with biophysical techniques is desired. The development of many fluorescence
      techniques, including superresolution fluorescence microscopy, has significantly
      enhanced our ability to spot proteins and other molecules in the crowded cellular
      environment. However, the observation of their structure and conformational
      changes while they attend their business is still very challenging. In principle,
      NMR and EPR spectroscopy can be used to investigate the conformation and dynamics
      of biological macromolecules in living cells. The development of in-cell magnetic
      resonance techniques has demonstrated the feasibility of this approach. Herein we
      review the different techniques with a focus on liquid-state in-cell NMR
      spectroscopy, provide an overview of applications, and discuss the challenges
      that lie ahead. 

PMID- 25070286
TI  - Abstracts of the British Society of Paediatric Dentistry Annual Scientific
      Meeting, 17-19 September 2014, London, UK.

PMID- 25070288
TI  - Children with chronic renal disease undergoing dialysis or conservative treatment
      -differences in structural and functional echocardiographic parameters.
AB  - Cardiac disease frequently occurs in children with chronic kidney disease (CKD)
      undergoing dialysis (DI), but it is not well studied in patients undergoing
      conservative treatment (CT). The aim of our study was to use echocardiography to
      analyze and compare the cardiac involvement of children with CKD undergoing DI or
      CT. METHODS: Seventy-one children with CKD were included; 41 undergoing DI and 30
      undergoing CT. There were 33 controls. Measurements of arterial pressure and
      structural and functional echocardiographic variables were obtained; the children
      were followed up for 18 months. Tests of comparison and multiple regression were
      used; significant if P < 0.05. RESULTS: Arterial hypertension (AH) was present in
      37 of 71 (52%) children with CKD: 27 (65.8%) in DI and 10 (33.3%) in CT (X2 =
      8.7; P = 0.003). An abnormal left ventricular geometric pattern was present in
      37/41 (90.3%) undergoing DI, 33 had left ventricular hypertrophy (LVH), and in
      14/30 (46.7%) undergoing CT, 5 had LVH. Ejection fraction was normal in all
      groups; diastolic function alteration (DFA) occurred in 28/41 (68.3%) children on
      DI and in 10/30 (33.3%) on CT (X2 = 9.2; P = 0.002). For children with CKD, DI (P
      = 0.002) and hypertension (P = 0.04) were associated with LVH; among those on DI,
      only AH was associated with LVH (P = 0.02). During the follow-up, 18 (43.9%)
      children undergoing DI had at least one cardiovascular event. CONCLUSION:
      Children with CKD undergoing CT had less cardiac involvement than those
      undergoing DI. LVH was associated with DI and AH in all children with CKD and
      with AH in those on DI.

PMID- 25070287
TI  - Skull base chondroid chordoma: atypical case manifesting as intratumoral
      hemorrhage and literature review.
AB  - OBJECTIVE: Chondroid chordoma (CC) is a rare but commonest subtype of chordoma
      with little reported clinical information. The present study summarizes and
      updates present knowledge of CC. METHODS: Literature search for demographic data
      and clinical appearance of cranial CCs except for those entirely confined to the
      sinonasal region. RESULTS: A total of 48 English language papers published from
      1968-2013 were retrieved describing 132 CCs as skull base tumors. The male-to
      female ratio was 1:1. The mean age at diagnosis was 43 years, predisposing to the
      third to fifth decades of life. The clival (34%) and spheno-occipital (29%)
      regions were the most frequent sites of origin followed by the sellar (12%) and
      sphenoid (5%) regions. Intratumoral calcification and bony erosion were
      identified as the characteristic neuroimaging findings. Surgical resection by the
      transcranial, transsphenoidal, transnasal, transpharyngeal, or transpalatal route
      with or without adjuvant radiotherapy was the main treatment option. The initial
      treatment outcome was satisfactory in 82% of cases with considerably better
      prognosis compared with typical chordomas. CONCLUSION: CC is a distinct entity to
      be discriminated from the typical type of chordoma. There are no distinguishing
      features on magnetic resonance imaging between CC and typical chordoma.
      Intratumoral calcification and concurrent bony erosion on neuroimaging should
      suggest the possibility of CC. Extensive surgical resection and adjuvant
      radiotherapy can achieve satisfactory outcome.

PMID- 25070289
TI  - Total mercury, cadmium and lead levels in main export fish of Sri Lanka.
AB  - Total mercury (Hg), cadmium (Cd) and lead (Pb) levels were determined in the
      muscle of four commercialised exported fish species Thunnus albacares (yellowfin
      tuna), Xiphias gladius (swordfish), Makaira indica (black marlin) and Lutjanus sp
      (red snapper) collected from the Indian Ocean, Sri Lanka, during July 2009-March
      2010 and measured by atomic absorption spectrophotometry. Results show that
      swordfish (n = 176) contained the highest total Hg (0.90 +/- 0.51 mg/kg) and Cd
      (0.09 +/- 0.13 mg/kg) levels, whereas yellowfin tuna (n = 140) contained the
      highest Pb levels (0.11 +/- 0.16 mg/kg). The lowest total Hg (0.16 +/- 0.11
      mg/kg), Cd (0.01 +/- 0.01 mg/kg) and Pb (0.04 +/- 0.04 mg/kg) levels were found
      in red snapper (n = 28). Black marlin (n = 24) contained moderate levels of total
      Hg (0.49 +/- 0.37), Cd (0.02 +/- 0.02) and Pb (0.05 +/- 0.05). Even though there
      are some concerns during certain months of the year, this study demonstrates the
      safety of main export fish varieties in terms of total Hg, Cd and Pb. 

PMID- 25070290
TI  - Temperature-dependent rheological property changes of thermoplastic gutta-percha
      root filling materials.
AB  - AIM: To compare the penetration resistance (PR) of six thermoplastic gutta-percha
      (GP) materials against needle penetration at different temperatures. METHODOLOGY:
      The PR of the following materials based on warm gutta-percha techniques, Beefill
      GP Cartridge (Beefill), GP Obturator-Hard/Medium/Soft (Dia-H, Dia-M, Dia-S),
      Obtura (Obtura) and Tactendo Gutta (Tactendo), was measured as a function of
      temperature change (from 30  degrees C to 200  degrees C). The PR was measured
      using a force gauge, mounted on a motor-driven micrometre stage, which pushed the
      penetration needle against GP in a glass cylinder at the designated temperatures.
      Data were analysed using Kruskal-Wallis anova and Duncan's multiple range tests
      at 5% significance. RESULTS: The mean PR values for all assessed materials ranged
      from 15.55 MPa to 26.02 MPa at 30  degrees C, decreased to 0.18-1.61 MPa at 60 
      degrees C, and finally reached 0.02-0.12 MPa at 200  degrees C. The Obtura had
      the highest PR values at most of the measured temperatures. At 40-60  degrees C,
      Obtura had the highest PR value (P < 0.05), and Tactendo had the lowest amongst
      the tested materials. At 70-200  degrees C, both the mean PR values and melt flow
      temperature (MFR) of Obtura, Dia-H and Dia-M were significantly higher than those
      of other materials (P < 0.05). CONCLUSIONS: The PR values were changed by both
      the heating temperature and the brand or type of GP materials tested. Each
      material was associated with drastic decreases before reaching 60  degrees C in
      different degrees, and Obtura had the highest PR at most of the measured
      temperatures.

PMID- 25070291
TI  - Two hour death in US execution is likely to lead to legal challenges.

PMID- 25070292
TI  - Safety evaluation of rabbit eyes on scleral collagen cross-linking by riboflavin
      and ultraviolet A.
AB  - BACKGROUND: To evaluate the safety of the scleral collagen cross-linking (CXL)
      transferred from corneal CXL in rabbit eyes using histology and
      electroretinography (ERG). METHODS: Stress-strain measurement was performed five
      rabbits 1 week after scleral CXL. Dark-adapted ERG was repeatedly applied on
      bilateral eyes of 10 rabbits before, and 1 week, 1 month and 3 months after the
      CXL operation. Histological analysis, terminal deoxynucleotidyl transferase dUTP
      nick-end labeling, the measurement of outer nuclear layer thickness and
      transmission electron microscopy were performed onto 15 rabbits at corresponding
      time points postoperatively. RESULTS: The mechanical and biochemical stability of
      rabbit scleral tissues was statistically increased after the scleral CXL (P =
      .00). However, the dark-adapted ERG amplitudes were statistically reduced 1 week,
      1 month and 3 months postoperatively (P < 0.05). Compared with the control eyes,
      apoptotic cells and ultrastructural changes can be found in the retinal layers of
      scleral cross-linked eyes. CONCLUSIONS: According to the electrophysiological and
      histopathological results, the current scleral CXL laboratory technique is not
      safe enough for the postoperative visual function of rabbit eyes.

PMID- 25070293
TI  - Risk and protective factors for depressive symptoms among American Indian older
      adults: adverse childhood experiences and social support.
AB  - OBJECTIVES: Despite efforts to promote health equity, many American Indian and
      Alaska Native (AI/AN) populations, including older adults, experience elevated
      levels of depression. Although adverse childhood experiences (ACE) and social
      support are well-documented risk and protective factors for depression in the
      general population, little is known about AI/AN populations, especially older
      adults. The purpose of this study was to examine factors related to depression
      among a sample of AI older adults in the midwest. METHOD: Data were collected
      using a self-administered survey completed by 233 AIs over the age of 50. The
      survey included standardized measures such as the Geriatric Depression Scale
      Short Form, ACE Questionnaire, and the Multidimensional Scale of Perceived Social
      Support. Hierarchical multivariate regression analyses were conducted to evaluate
      the main hypotheses of the study. RESULTS: Two dimensions of ACE (i.e., childhood
      neglect, household dysfunction) were positively associated with depressive
      symptoms; social support was negatively associated with depressive symptoms.
      Perceived health and living alone were also significant predictors. CONCLUSION:
      ACE may play a significant role in depression among AI/AN across the life course
      and into old age. Social support offers a promising mechanism to bolster
      resilience among AI/AN older adults.

PMID- 25070294
TI  - BRAF mutation status is an independent prognostic factor for resected stage IIIB
      and IIIC melanoma: implications for melanoma staging and adjuvant therapy.
AB  - BACKGROUND: 5-year survival for melanoma metastasis to regional lymph nodes
      (American Joint Committee on Cancer stage III) is <50%. Knowledge of outcomes
      following therapeutic lymphadenectomy for stage III melanoma related to BRAF
      status may guide adjuvant use of BRAF/MEK inhibitors along with established and
      future therapies. AIMS: To determine patterns of melanoma recurrence and survival
      following therapeutic lymph node dissection (TLND) associated with oncogenic
      mutations. METHODS: DNA was obtained from patients who underwent TLND and had ?2
      positive nodes, largest node >3cm or extracapsular invasion. Mutations were
      detected using an extended Sequenom MelaCARTA panel. RESULTS: Mutations were most
      commonly detected in BRAF (57/124 [46%] patients) and NRAS (26/124 [21%]
      patients). Patients with BRAF mutations had higher 3-year recurrence rate (77%)
      versus 54% for BRAF wild-type patients (hazard ratio (HR) 1.8, p=0.008). The only
      prognostically significant mutations occurred in BRAF: median recurrence-free
      (RFS) and disease-specific survival (DSS) for BRAF mutation patients was 7 months
      and 16 months, versus 19 months and not reached for BRAF wild-type patients,
      respectively. Multivariate analysis identified BRAF mutant status and number of
      positive lymph nodes as the only independent prognostic factors for RFS and DSS.
      CONCLUSIONS: Patients with BRAF mutations experienced rapid progression of
      metastatic disease with locoregional recurrence rarely seen in isolation,
      supporting incorporation of BRAF status into melanoma staging and use of BRAF/MEK
      inhibitors post-TLND.

PMID- 25070295
TI  - Uro-oncology multidisciplinary meetings at an Australian tertiary referral centre
      -impact on clinical decision-making and implications for patient inclusion.
AB  - OBJECTIVES: To analyse the impact of the uro-oncology multidisciplinary meeting
      (MDM) at an Australian tertiary centre on patient management decisions, and to
      develop criteria for patient inclusion in MDMs. METHODS: Over a 3-month period,
      all cases presented at our weekly uro-oncology MDM were prospectively assessed,
      by asking the presenting clinician to state their provisional management plans
      and comparing this with the subsequent consensus decision. The impact of the MDM
      was graded as high if there was a major change in the management plan or if a
      plan was developed where there was none. RESULTS: Over the study period, 120
      discussions about 107 patients were recorded. Prostate, urothelial, kidney and
      testis cancer represented 46 (38.3%), 36 (30%), 26 (21.6%) and 12 (10%) of the
      discussions, respectively. The MDM made high impact changes to the original plan
      in 32 (26.7%) cases. High impact changes were nearly twice as likely to occur in
      patients with metastatic disease as in those without metastases (P < 0.05).
      Primary cross referral between disciplines occurred in 40 (33.3%) cases,
      including 66.7% of testicular and 42% of bladder cancers but only 26% of prostate
      and 19% of kidney cancers (P < 0.02). CONCLUSIONS: The uro-oncology MDM alters
      management plans in about one-quarter of cases. Additionally, MDMs also serve
      other purposes, such as cross-referral or consideration for clinical trials.
      Patients should be discussed in MDMs if multimodal therapy may be required,
      clinical trial eligibility is being considered or if metastasis or recurrence is
      noted.

PMID- 25070296
TI  - A general catalyst for Suzuki-Miyaura and Sonogashira reactions of aryl and
      heteroaryl chlorides in water.
AB  - We report the synthesis of 2-(3-sulfonatomesityl)-5
      sulfonatoindenyl)dicyclohexylphosphine hydrate sodium salt and its use in
      palladium-catalyzed Suzuki-Miyaura and Sonogashira coupling reactions in water
      (and biphasic water-organic solvent mixtures) to prepare a variety of
      functionalized biaryls and aryl alkynes in excellent yield. 

PMID- 25070297
TI  - Primary cutaneous balloon cell melanoma: a very rare variant.

PMID- 25070299
TI  - Neonatal abstinence syndrome.
AB  - Neonatal abstinence syndrome (NAS) is a result of the sudden discontinuation of
      fetal exposure to substances that were used or abused by the mother during
      pregnancy. Withdrawal from licit or illicit substances is becoming more common
      among neonates in both developed and developing countries. NAS continues to be an
      important clinical entity throughout much of the world. NAS leads to a
      constellation of signs and symptoms involving multiple systems. The
      pathophysiology of NAS is not completely understood. Urine or meconium
      confirmation may assist the diagnosis and management of NAS. The Finnegan scoring
      system is commonly used to assess the severity of NAS; scoring can be helpful for
      initiating, monitoring, and terminating treatment in neonates. Nonpharmacological
      care is the initial treatment option, and pharmacological treatment is required
      if an improvement is not observed after nonpharmacological measures or if the
      infant develops severe withdrawal. Morphine is the most commonly used drug in the
      treatment of NAS secondary to opioids. An algorithmic approach to the management
      of infants with NAS is suggested. Breastfeeding is not contraindicated in NAS,
      unless the mother is taking street drugs, is involved in polydrug abuse, or is
      infected with HIV. Future studies are required to assess the long-term effects of
      NAS on children after prenatal exposure. 

PMID- 25070300
TI  - Brain injury and altered brain growth in preterm infants: predictors and
      prognosis.
AB  - BACKGROUND: To define the nature and frequency of brain injury and brain growth
      impairment in very preterm (VPT) infants by using MRI at term-equivalent age and
      to relate these findings to perinatal risk factors and 2-year neurodevelopmental
      outcomes. METHODS: MRI scans at term-equivalent age from 3 VPT cohorts (n = 325)
      were reviewed. The severity of brain injury, including periventricular
      leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain
      growth was assessed by using measures of biparietal width (BPW) and
      interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed
      across all cohorts (n = 297) by using the Bayley Scales of Infant Development,
      Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development,
      Third Edition (Bayley-III), and evaluation for cerebral palsy. RESULTS: Of 325
      infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury.
      Severe brain injury was more common in infants with lower Apgar scores,
      necrotizing enterocolitis, inotropic support, and patent ductus arteriosus.
      Severe brain injury was associated with delayed cognitive and motor development
      and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic
      support, patent ductus arteriosus, necrotizing enterocolitis, prolonged
      parenteral nutrition, and oxygen at 36 weeks and was associated with delayed
      cognitive development. In contrast, increased interhemispheric distance was
      related to male gender, dexamethasone use, and severe brain injury. It was also
      associated with reduced cognitive development, independent of BPW. CONCLUSIONS:
      At term-equivalent age, VPT infants showed both brain injury and impaired brain
      growth on MRI. Severe brain injury and impaired brain growth patterns were
      independently associated with perinatal risk factors and delayed cognitive
      development.

PMID- 25070301
TI  - Delayed diagnosis of critical congenital heart defects: trends and associated
      factors.
AB  - OBJECTIVE: We aimed to examine trends in timing of diagnosis of critical
      congenital heart defects (CCHDs) and factors associated with delayed diagnosis
      (diagnosis after discharge home following delivery). METHODS: We examined a
      population-based retrospective cohort of CCHD cases among live births identified
      through the Massachusetts Birth Defects Monitoring Program. Congenital heart
      defects were considered critical if the infant received corrective surgery,
      interventional catheterization, palliative care, or died as a result of the
      defect within 12 months of birth. Timing of initial diagnosis was classified as
      prenatal, postnatal before discharge home, or delayed. Demographic, perinatal,
      and mortality information was obtained from the Registry of Vital Records and
      Statistics. Prevalence ratios (PRs) were used to examine associations with
      delayed diagnosis. RESULTS: Among 460 467 live births to Massachusetts residents
      between 2004 and 2009, we identified 916 CCHD cases, of which 126 (13.8%) had
      delayed diagnosis. Rates of prenatal CCHD diagnosis increased from 44.9% in 2004
      to 63.8% in 2009, whereas rates of delayed diagnosis decreased from 17.1% to
      10.6% over the same time period. Among cases with delayed diagnosis, the most
      common defects were coarctation, pulmonary valve stenosis, and tetralogy of
      Fallot. Delayed diagnosis was associated with delivery outside a tertiary
      hospital (adjusted PR: 3.6 [95% confidence interval: 2.5-5.2]) and isolated CCHD
      (adjusted PR: 1.7 [95% confidence interval: 1.1-2.7]). CONCLUSIONS: Despite
      increasing prenatal diagnosis of CCHDs, delayed diagnosis still occurs in over
      10% of cases. Understanding factors associated with delayed diagnosis could help
      to improve prenatal and postnatal screening efforts, including pulse oximetry
      testing.

PMID- 25070303
TI  - Teaching the essentials of "well-child care": inspiring proficiency and passion.

PMID- 25070302
TI  - Growth after adenotonsillectomy for obstructive sleep apnea: an RCT.
AB  - BACKGROUND AND OBJECTIVES: Adenotonsillectomy for obstructive sleep apnea
      syndrome (OSAS) may lead to weight gain, which can have deleterious health
      effects when leading to obesity. However, previous data have been from
      nonrandomized uncontrolled studies, limiting inferences. This study examined the
      anthropometric changes over a 7-month interval in a randomized controlled trial
      of adenotonsillectomy for OSAS, the Childhood Adenotonsillectomy Trial. METHODS:
      A total of 464 children who had OSAS (average apnea/hypopnea index [AHI]
      5.1/hour), aged 5 to 9.9 years, were randomized to Early Adenotonsillectomy (eAT)
      or Watchful Waiting and Supportive Care (WWSC). Polysomnography and anthropometry
      were performed at baseline and 7-month follow-up. Multivariable regression
      modeling was used to predict the change in weight and growth indices. RESULTS:
      Interval increases in the BMI z score (0.13 vs. 0.31) was observed in both the
      WWSC and eAT intervention arms, respectively, but were greater with eAT (P <
      .0001). Statistical modeling showed that BMI z score increased significantly more
      in association with eAT after considering the influences of baseline weight and
      AHI. A greater proportion of overweight children randomized to eAT compared with
      WWSC developed obesity over the 7-month interval (52% vs. 21%; P < .05). Race,
      gender, and follow-up AHI were not significantly associated with BMI z score
      change. CONCLUSIONS: eAT for OSAS in children results in clinically significant
      greater than expected weight gain, even in children overweight at baseline. The
      increase in adiposity in overweight children places them at further risk for OSAS
      and the adverse consequences of obesity. Monitoring weight, nutritional
      counseling, and encouragement of physical activity should be considered after eAT
      for OSAS.

PMID- 25070305
TI  - Flawed data render findings meaningless.

PMID- 25070304
TI  - Updated guidance for palivizumab prophylaxis among infants and young children at
      increased risk of hospitalization for respiratory syncytial virus infection.
AB  - Guidance from the American Academy of Pediatrics (AAP) for the use of palivizumab
      prophylaxis against respiratory syncytial virus (RSV) was first published in a
      policy statement in 1998. Guidance initially was based on the result from a
      single randomized, placebo-controlled clinical trial conducted in 1996-1997
      describing an overall reduction in RSV hospitalization rate from 10.6% among
      placebo recipients to 4.8% among children who received prophylaxis. The results
      of a second randomized, placebo-controlled trial of children with hemodynamically
      significant heart disease were published in 2003 and revealed a reduction in RSV
      hospitalization rate from 9.7% in control subjects to 5.3% among prophylaxis
      recipients. Because no additional controlled trials regarding efficacy were
      published, AAP guidance has been updated periodically to reflect the most recent
      literature regarding children at greatest risk of severe disease. Since the last
      update in 2012, new data have become available regarding the seasonality of RSV
      circulation, palivizumab pharmacokinetics, the changing incidence of
      bronchiolitis hospitalizations, the effects of gestational age and other risk
      factors on RSV hospitalization rates, the mortality of children hospitalized with
      RSV infection, and the effect of prophylaxis on wheezing and palivizumab
      resistant RSV isolates. These data enable further refinement of AAP guidance to
      most clearly focus on those children at greatest risk. 

PMID- 25070306
TI  - Updated recommendations on the use of meningococcal vaccines.
AB  - Since the last policy statement from the American Academy of Pediatrics (AAP)
      concerning meningococcal vaccine was published in 2011, 2 meningococcal conjugate
      vaccines have been licensed for use in infants (Hib-MenCY-TT and MenACWY-CRM).
      The Centers for Disease Control and Prevention (CDC) has published new
      recommendations, "Prevention and Control of Meningococcal Disease:
      Recommendations of the Advisory Committee on Immunization Practices," which have
      been endorsed by the AAP. However, the CDC recommendations were published before
      licensure of MenACWY-CRM for infant use. This policy statement updates the AAP
      recommendations for use of meningococcal vaccines in children and adolescents. A
      more comprehensive review of background and technical information can be found in
      the CDC publication. 

PMID- 25070308
TI  - Gestational age and risk of venous thromboembolism from birth through young
      adulthood.
AB  - BACKGROUND: Preterm birth has been associated with increased risk of venous
      thromboembolism (VTE) in infancy, but the longer-term risk is unknown. Our aim
      was to examine this association from birth through young adulthood. METHODS:
      National cohort study of 3,571,574 individuals who were live-born in Sweden from
      1973 through 2008, including 206,844 born preterm (gestational age <37 weeks),
      and followed up to 2010 (ages 0-38 years). The main outcome was VTE. RESULTS: A
      total of 7519 (0.2%) individuals were diagnosed with VTE in 70.8 million person
      years of follow-up. Low gestational age at birth was associated with VTE in
      infancy (ages <1 year: adjusted hazard ratio 47.16 [95% confidence interval 21.30
      104.42] for 22 to 27 weeks, 5.54 [2.53-12.12] for 28 to 33 weeks, 3.54 [2.07
      6.06] for 34 to 36 weeks, 1.00 for 37 to 41 weeks [reference]), early childhood
      (ages 1-5 years), and young adulthood (ages 18-38 years: adjusted hazard ratio
      2.76 [1.43-5.31] for 22 to 27 weeks, 1.53 [1.24-1.89] for 28 to 33 weeks, 1.24
      [1.10-1.40] for 34 to 36 weeks, and 1.00 for 37 to 41 weeks [reference]), but not
      in late childhood (ages 6-12 years). Very preterm (<34 weeks) but not late
      preterm birth (34-36 weeks) was also associated with VTE in adolescence (ages 13
      17 years). After further adjustment for comorbidities, these associations were
      attenuated, but most remained significantly elevated. CONCLUSIONS: In this large
      national cohort, low gestational age at birth was associated with increased risk
      of VTE in infancy, early childhood, and young adulthood.

PMID- 25070309
TI  - Comanagement of medically complex children by subspecialists, generalists, and
      care coordinators.

PMID- 25070310
TI  - Cost-benefit analysis of a medical emergency team in a children's hospital.
AB  - OBJECTIVES: Medical emergency teams (METs) can reduce adverse events in
      hospitalized children. We aimed to model the financial costs and benefits of
      operating an MET and determine the annual reduction in critical deterioration
      (CD) events required to offset MET costs. METHODS: We performed a single-center
      cohort study between July 1, 2007 and March 31, 2012 to determine the cost of CD
      events (unplanned transfers to the ICU with mechanical ventilation or
      vasopressors in the 12 hours after transfer) as compared with transfers to the
      ICU without CD. We then performed a cost-benefit analysis evaluating varying MET
      compositions and staffing models (freestanding or concurrent responsibilities) on
      the annual reduction in CD events needed to offset MET costs. RESULTS: Patients
      who had CD cost $99,773 (95% confidence interval, $69,431 to $130,116; P < .001)
      more during their post-event hospital stay than transfers to the ICU that did not
      meet CD criteria. Annual MET operating costs ranged from $287,145 for a nurse and
      respiratory therapist team with concurrent responsibilities to $2,358,112 for a
      nurse, respiratory therapist, and ICU attending physician freestanding team. In
      base-case analysis, a nurse, respiratory therapist, and ICU fellow team with
      concurrent responsibilities cost $350,698 per year, equivalent to a reduction of
      3.5 CD events. CONCLUSIONS: CD is expensive. The costs of operating a MET can
      plausibly be recouped with a modest reduction in CD events. Hospitals reimbursed
      with bundled payments could achieve real financial savings by reducing CD with an
      MET.

PMID- 25070311
TI  - Sensitivity of the limited view follow-up skeletal survey.
AB  - BACKGROUND AND OBJECTIVE: Reducing radiation exposure to minimize risk has been
      emphasized in recent years. In child abuse, the risk of missing occult injuries
      is often believed to outweigh radiation risk associated with skeletal surveys.
      Our hypothesis was that there would be no clinically significant difference in
      results from a limited view, follow-up skeletal survey (SS2) protocol, which
      omits spine and pelvis views unless these views have findings on the initial
      skeletal survey (SS1), compared with a traditional SS2 protocol for radiographic
      evaluation of suspected physical abuse. METHODS: This study was a retrospective
      record review involving 5 child protection teams. Consultations for suspected
      physical abuse were reviewed to identify subjects <24 months of age who had an
      SS1 and a traditional SS2. The results of these studies were compared to identify
      subjects in which newly identified spine and pelvis fractures (fractures seen
      only on SS2 and not on SS1) would have been missed by using a limited view SS2
      protocol. RESULTS: We identified 534 study subjects. Five subjects had newly
      identified spine fractures, and no subjects had newly identified pelvis fractures
      on traditional SS2 studies. Only 1 subject with a newly identified spine fracture
      would have been missed with the limited view SS2 protocol used in this study
      (0.2% [95% confidence interval: <0.005-1.0]). None of the newly identified
      fractures changed the abuse-related diagnosis. CONCLUSIONS: We found no
      clinically significant difference in the results of a limited view SS2 protocol
      versus a traditional SS2 protocol for radiographic evaluation of suspected abuse.

PMID- 25070312
TI  - Minimal lymphatic leakage in an infant with chylothorax detected by
      lymphoscintigraphy SPECT/CT.
AB  - A 7-month-old girl with history of persistent left chylous pleural effusion was
      referred for lymphoscintigraphy. A previous chest computed tomography (CT) scan
      demonstrated a small to moderate-sized left pleural effusion but could not
      identify the lymphatic leakage site. Lymphoscintigraphy using filtered (99m)Tc
      sulfur colloid showed minimal focal activity in the lower chest. A correlative
      single-photon emission computed tomography (SPECT)/CT localized this activity to
      distal paraesophageal region, being highly suggestive of the site of lymphatic
      leakage. Subsequent lymphangiography confirmed these findings, revealing an
      abnormal lymphatic branch at the level of T10 and T11 vertebrae with retrocrural
      extravasation toward the left hemithorax. Thoracic duct embolization was
      accomplished at and proximal to the site of chyle leak using a platinum coil and
      n-Butyl cyanoacrylate glue. The patient was followed up for >24 months and
      demonstrated no recurrence of pleural effusion. No ascites or other complications
      related to the procedure were noted. The case demonstrates that (99m)Tc sulfur
      colloid lymphoscintigraphy SPECT/CT can be a useful modality for detecting the
      chyle leakage site in children with chylothorax even when the amount of leakage
      is minimal. 

PMID- 25070313
TI  - Outcomes in multifocal neuroblastoma as part of the neurocristopathy syndrome.
AB  - The neurocristopathy syndrome occurs because of a germline mutation of the paired
      like homeobox 2b (PHOX2B) gene at 4p12, a neurogenesis regulator gene. The result
      is abnormal neural crest cell development resulting in congenital central
      hypoventilation syndrome, Hirschsprung disease, and neuroblastoma (NB), which is
      often multifocal and disseminated in its presentation. Previously, such
      widespread disease was regarded as highly aggressive and treated either with
      palliative intent or, conversely, with very intense, high-dose chemotherapy. We
      now present a patient who had neurocristopathy syndrome who had multifocal NB
      associated with an underlying germline PHOX2B mutation. He was treated
      conservatively with surgery and low-dose chemotherapy. After treatment he had
      extensive residual disease that has continued to mature despite no further
      treatment. A literature review identified 26 similar patients presenting with
      multifocal NB as part of the neurocristopathy syndrome. In all cases the NB
      behaved in an indolent manner with no deaths from tumor reported when patients
      received appropriate treatment. These provocative findings suggest for the first
      time that children who have neurocristopathy-associated NB should be treated
      conservatively, despite the aggressive appearance of their disease. 

PMID- 25070315
TI  - Updated guidance for palivizumab prophylaxis among infants and young children at
      increased risk of hospitalization for respiratory syncytial virus infection.
AB  - Palivizumab was licensed in June 1998 by the Food and Drug Administration for the
      reduction of serious lower respiratory tract infection caused by respiratory
      syncytial virus (RSV) in children at increased risk of severe disease. Since that
      time, the American Academy of Pediatrics has updated its guidance for the use of
      palivizumab 4 times as additional data became available to provide a better
      understanding of infants and young children at greatest risk of hospitalization
      attributable to RSV infection. The updated recommendations in this policy
      statement reflect new information regarding the seasonality of RSV circulation,
      palivizumab pharmacokinetics, the changing incidence of bronchiolitis
      hospitalizations, the effect of gestational age and other risk factors on RSV
      hospitalization rates, the mortality of children hospitalized with RSV infection,
      the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates.
      This policy statement updates and replaces the recommendations found in the 2012
      Red Book. 

PMID- 25070316
TI  - Closer to understanding the value proposition for medical emergency teams.

PMID- 25070317
TI  - A multicenter cohort study of treatments and hospital outcomes in neonatal
      abstinence syndrome.
AB  - OBJECTIVES: To compare pharmacologic treatment strategies for neonatal abstinence
      syndrome (NAS) with respect to total duration of opioid treatment and length of
      inpatient hospital stay. METHODS: We conducted a cohort analysis of late preterm
      and term neonates who received inpatient pharmacologic treatment of NAS at one of
      20 hospitals throughout 6 Ohio regions from January 2012 through July 2013.
      Physicians managed NAS using 1 of 6 regionally based strategies. RESULTS: Among
      547 pharmacologically treated infants, we documented 417 infants managed using an
      established NAS weaning protocol and 130 patients managed without protocol-driven
      weaning. Regardless of the treatment opioid chosen, when we accounted for
      hospital variation, infants receiving protocol-based weans experienced a
      significantly shorter duration of opioid treatment (17.7 vs. 32.1 days, P <
      .0001) and shorter hospital stay (22.7 vs. 32.1 days, P = .004). Among infants
      receiving protocol-based weaning, there was no difference in the duration of
      opioid treatment or length of stay when we compared those treated with morphine
      with those treated with methadone. Additionally, infants treated with
      phenobarbital were treated with the drug for a longer duration among those
      following a morphine-based compared with methadone-based weaning protocol. (P <=
      .002). CONCLUSIONS: Use of a stringent protocol to treat NAS, regardless of the
      initial opioid chosen, reduces the duration of opioid exposure and length of
      hospital stay. Because the major driver of cost is length of hospitalization, the
      implications for a reduction in cost of care for NAS management could be
      substantial.

PMID- 25070318
TI  - Longitudinal profiles of adaptive behavior in fragile X syndrome.
AB  - OBJECTIVE: To examine longitudinally the adaptive behavior patterns in fragile X
      syndrome. METHOD: Caregivers of 275 children and adolescents with fragile X
      syndrome and 225 typically developing children and adolescents (2-18 years) were
      interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part
      of a prospective longitudinal study. RESULTS: Standard scores of adaptive
      behavior in people with fragile X syndrome are marked by a significant decline
      over time in all domains for males and in communication for females.
      Socialization skills are a relative strength as compared with the other domains
      for males with fragile X syndrome. Females with fragile X syndrome did not show a
      discernible pattern of developmental strengths and weaknesses. CONCLUSIONS: This
      is the first large-scale longitudinal study to show that the acquisition of
      adaptive behavior slows as individuals with fragile X syndrome age. It is
      imperative to ensure that assessments of adaptive behavior skills are part of
      intervention programs focusing on childhood and adolescence in this condition.

PMID- 25070319
TI  - Bone mineral content in patients with congenital generalized lipodystrophy is
      unaffected by metreleptin replacement therapy.
AB  - CONTEXT: Leptin alters bone and mineral metabolism in rodents, but this has not
      been verified in humans. PATIENTS with congenital generalized lipodystrophy (CGL)
      have low leptin due to deficient adipose mass and serve as models of leptin
      deficiency and replacement. OBJECTIVE: To study the effects of recombinant human
      methionyl leptin (metreleptin) on bone mineral content (BMC) and mineral
      metabolism. DESIGN AND SETTING: An open-label nonrandomized study at the National
      Institutes of Health. PATIENTS: Thirty-one patients with CGL (ages 4.3 to 46.7
      y). INTERVENTION: Metreleptin (0.06 to 0.24 mg/kg/d) for 6 months to 11 years.
      OUTCOME MEASURES: BMC was assessed by dual-energy x-ray absorptiometry. SD scores
      (SDS) for BMC were calculated based on height, race, sex, and age using
      population normative data. Calcium, phosphorus, PTH, 25-hydroxyvitamin D, and
      1,25-dihydroxyvitamin D were measured at baseline and follow-up. RESULTS: At
      baseline, patients demonstrated significantly increased total body less head BMC
      (mean SDS, 1.8 +/- 0.7), height (mean SDS, 1.3 +/- 1.3), and lean mass index,
      defined as lean body mass per height squared (mean SDS, 1.5 +/- 0.83), vs
      population normative data. No change in total body less head BMC was observed
      after metreleptin. Lean mass index decreased with metreleptin. Serum calcium
      decreased with metreleptin, but remained within normal limits. No changes were
      seen in phosphorus, PTH, or vitamin D. CONCLUSIONS: In contrast to rodent models,
      CGL patients have increased BMC in the leptin-deficient state, which does not
      change with leptin replacement. The high BMC in these patients is partially
      explained by high lean mass and tall stature.

PMID- 25070320
TI  - Genetic variants in CYP2R1, CYP24A1, and VDR modify the efficacy of vitamin D3
      supplementation for increasing serum 25-hydroxyvitamin D levels in a randomized
      controlled trial.
AB  - CONTEXT: Adequate serum 25-hydroxyvitamin D concentrations, [25(OH)D], are
      required for optimal bone health, and low levels are associated with chronic
      diseases. OBJECTIVE: We investigated whether 41 candidate single nucleotide
      polymorphisms (SNPs) in vitamin D and calcium pathway genes (GC, DHCR7, CYP2R1,
      CYP27B1, CYP24A1, VDR, and CASR) are associated with [25(OH)D] or modify the
      increase in [25(OH)D] from vitamin D3 supplementation. DESIGN AND SETTING:
      Baseline and year 1 [25(OH)D] measurements from a randomized controlled trial
      conducted at 11 clinical centers in the United States. PARTICIPANTS: A total of
      1787 healthy non-Hispanic white participants aged 45-75 years. INTERVENTIONS:
      Vitamin D3 (1000 IU/d), calcium carbonate (1200 mg/d elemental), both, or
      placebo. MAIN OUTCOME MEASURES: Genotype main effects and interactions with
      vitamin D3 treatment estimated using multiple linear regression. RESULTS: The
      baseline serum [25(OH)D] was 25.4 +/- 8.7 ng/mL (mean +/- SD). Associations with
      baseline levels were discovered for SNPs in CYP24A1 (rs2209314, rs2762939) and
      confirmed for SNPs in GC and CYP2R1. After 1 year, [25(OH)D] increased on average
      by 6.1 +/- 8.9 ng/mL on vitamin D3 treatment and decreased by 1.1 +/- 8.4 ng/mL
      on placebo. The increase in [25(OH)D] due to vitamin D3 supplementation was
      modified by genotypes at rs10766197 near CYP2R1, rs6013897 near CYP24A1, and
      rs7968585 near VDR. CONCLUSIONS: The increase in [25(OH)D] attributable to
      vitamin D3 supplementation may vary according to common genetic differences in
      vitamin D 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), and the vitamin D
      receptor (VDR) genes. These findings have implications for achieving optimal
      vitamin D status and potentially for vitamin D-related health outcomes.

PMID- 25070321
TI  - Characterization of cefalexin degradation capabilities of two Pseudomonas strains
      isolated from activated sludge.
AB  - Pharmaceuticals have recently been regarded as contaminants of emerging concern.
      To date, there is limited knowledge about antibiotic-degrading microorganisms in
      conventional activated sludge treatment systems and their characteristics toward
      antibiotic degradation especially in the presence of a pharmaceutical mixture. As
      such, antibiotic-degrading microorganisms were investigated and isolated from the
      activated sludge, and their degradation capabilities were evaluated. Two strains
      of cefalexin-degrading bacteria CE21 and CE22 were isolated and identified as
      Pseudomonas sp. in the collected activated sludge. Strain CE22 was able to
      degrade over 90% of cefalexin, while CE21 was able to remove 46.7% of cefalexin
      after incubation for 24h. The removal efficiency of cefalexin by CE22, different
      from that of CE21, was not significantly affected by an increase in cefalexin
      concentration, even up to 10ppm, however the presence of 1ppm of other
      pharmaceuticals had a significant effect on the degradation of cefalexin by CE22,
      but no significant effect on CE21. The degradation product of cefalexin by the
      two strains was identified to be 2-hydroxy-3-phenyl pyrazine. Our results also
      indicated that CE21 and CE22 were able to degrade caffeine, salicylic acid and
      chloramphenicol. Moreover, CE21 was found to be capable of eliminating
      sulfamethoxazole and naproxen. 

PMID- 25070323
TI  - Scalable cardiac differentiation of human pluripotent stem cells as microwell
      generated, size controlled three-dimensional aggregates.
AB  - The formation of cells into more physiologically relevant three-dimensional
      multicellular aggregates is an important technique for the differentiation and
      manipulation of stem cells and their progeny. As industrial and clinical
      applications for these cells increase, it will be necessary to execute this
      procedure in a readily scalable format. We present here a method employing
      microwells to generate large numbers of human pluripotent stem cell aggregates
      and control their subsequent differentiation towards a cardiac fate. 

PMID- 25070322
TI  - Second generation codon optimized minicircle (CoMiC) for nonviral reprogramming
      of human adult fibroblasts.
AB  - The ability to induce pluripotency in somatic cells is one of the most important
      scientific achievements in the fields of stem cell research and regenerative
      medicine. This technique allows researchers to obtain pluripotent stem cells
      without the controversial use of embryos, providing a novel and powerful tool for
      disease modeling and drug screening approaches. However, using viruses for the
      delivery of reprogramming genes and transcription factors may result in
      integration into the host genome and cause random mutations within the target
      cell, thus limiting the use of these cells for downstream applications. To
      overcome this limitation, various non-integrating techniques, including Sendai
      virus, mRNA, minicircle, and plasmid-based methods, have recently been developed.
      Utilizing a newly developed codon optimized 4-in-1 minicircle (CoMiC), we were
      able to reprogram human adult fibroblasts using chemically defined media and
      without the need for feeder cells. 

PMID- 25070324
TI  - Preparation and characterization of circulating angiogenic cells for tissue
      engineering applications.
AB  - Circulating angiogenic cells (CACs) are a heterogeneous cell population of bone
      marrow (BM) origin. These cells are most commonly derived from the peripheral
      blood, bone marrow, and cord blood, and are one of the leading candidates for
      promoting vascularization in tissue engineering therapies. CACs can be isolated
      by culturing peripheral blood mononuclear cells (PBMCs) on fibronectin or by flow
      cytometry to obtain more specific subpopulations. Here we will describe how to
      generate a population of CACs, and how to characterize the cells and confirm
      their phenotype. Also, we will provide select methods that can be used to assess
      the angiogenic and endothelial cell-like properties of the CACs. 

PMID- 25070325
TI  - Isolation and expansion of c-kit-positive cardiac progenitor cells by magnetic
      cell sorting.
AB  - Cell therapy techniques are a promising option for tissue regeneration;
      especially in cases such as heart failure where transplantation is limited by
      donor availability. Multiple cell types have been examined for myocardial
      regeneration, including mesenchymal stem cells (and other bone marrow-derived
      cells), induced pluripotent stem cells, embryonic stem cells, cardiosphere
      derived cells, and cardiac progenitor cells (CPCs). CPCs are multipotent and
      clonogenic, can be harvested from mature tissue, and have the distinct advantages
      of autologous transplant and lack of tumor formation in a clinical setting. Here
      we focus on the isolation, expansion, and myocardial differentiation of rat CPCs.
      Brief adaptations of the protocol for isolation from mouse and human tissue are
      also provided. 

PMID- 25070326
TI  - Synthesis of aliphatic polyester hydrogel for cardiac tissue engineering.
AB  - Despite clinical advances, ischemic heart disease continues to be a major cause
      of morbidity and mortality worldwide. Prolonged cardiac ischemia and loss of
      cardiomyocytes frequently result in progressive pathological remodeling of the
      myocardium. If the heart is unable to adapt, patients may succumb to terminal
      heart failure. Cardiac tissue regeneration combining biodegradable biomaterials
      and stem cells has emerged as a new approach to restore heart function.
      Biomaterials, including injectable hydrogels and spongy scaffolds, can facilitate
      stem cell engraftment and survival and prevent adverse ventricular remodeling.
      Promising early results with injectable, biodegradable hydrogels for cardiac
      repair have provided new opportunities for designing innovative therapies to
      treat injured hearts. Hydrogels can be made from natural or synthetic polymers
      and have a water content, flexibility, and other physiochemical characteristics
      similar to those of living tissue, which makes them excellent candidates for
      tissue repair. In addition, hydrogels can be used as a vehicle to deliver
      cytokines or cells to the heart and can be employed to encapsulate biological
      macromolecules or cells and release them into the surrounding tissues during
      degradation. Hydrogels undergo physicochemical modifications in response to
      changes in temperature or pH, depending upon their polymer composition,
      converting from a liquid to a gel. The gel form retains cytokine molecules,
      allows their prolonged, controlled release, and preserves their bioactivity for
      extended periods. Polyethylene glycol is a water-soluble, biocompatible polymer
      that has negligible immunogenicity and can produce efficient conjugation of
      hydrogels to growth factors. In this chapter, we provide insight into the
      composition, polymerization, and use of a temperature-sensitive, biodegradable,
      aliphatic polyester hydrogel that transforms to a gel at physiological
      temperatures and is a potential candidate for cardiac tissue regeneration.

PMID- 25070327
TI  - Fabrication of PEGylated fibrinogen: a versatile injectable hydrogel biomaterial.
AB  - Hydrogels are one of the most versatile biomaterials in use for tissue
      engineering and regenerative medicine. They are assembled from either natural or
      synthetic polymers, and their high water content gives these materials practical
      advantages in numerous biomedical applications. Semisynthetic hydrogels, such as
      those that combine synthetic and biological building blocks, have the added
      advantage of controlled bioactivity and material properties. In myocardial
      regeneration, injectable hydrogels premised on a semisynthetic design are
      advantageous both as bioactive bulking agents and as a delivery vehicle for
      controlled release of bioactive factors and/or cardiomyocytes. A new
      semisynthetic hydrogel based on PEGylated fibrinogen has been developed to
      address the many requirements of an injectable biomaterial in cardiac
      restoration. This chapter highlights the fundamental aspects of making this
      biomimetic hydrogel matrix for cardiac applications. 

PMID- 25070328
TI  - Natural cardiac extracellular matrix hydrogels for cultivation of human stem cell
      derived cardiomyocytes.
AB  - Biomaterial scaffolds made of natural and synthetic materials are designed to
      serve as a structural and informational template for cell attachment and tissue
      formation. The use of native extracellular matrix (ECM) is of special interest
      for the culture of cardiac stem and progenitor cells due to the presence of
      intrinsic regulatory factors regulating cardiac function. We describe here how to
      obtain native ECM hydrogels from porcine hearts for the culture of human
      embryonic, induced pluripotent, and somatic stem cells for cardiac tissue
      engineering and regenerative medicine applications. 

PMID- 25070329
TI  - Magnetically actuated alginate scaffold: a novel platform for promoting tissue
      organization and vascularization.
AB  - Among the greatest hurdles hindering the successful implementation of tissue
      engineered cardiac patch as a therapeutic strategy for myocardial repair is the
      know-how to promote its rapid integration into the host. We previously
      demonstrated that prevascularization of the engineered cardiac patch improves
      cardiac repair after myocardial infarction (MI); the mature vessel networks were
      generated by including affinity-bound angiogenic factors in the patch and its
      transplantation on the blood vessel-enriched omentum. Here, we describe a novel
      in vitro strategy to promote the formation of capillary-like networks in cell
      constructs without supplementing with angiogenic factors. Endothelial cells (ECs)
      were seeded into macroporous alginate scaffolds impregnated with magnetically
      responsive nanoparticles (MNPs), and after pre-culture for 24 h under standard
      conditions the constructs were subjected to an alternating magnetic field of 40
      Hz for 7 days. The magnetic stimulation per se promoted EC organization into
      capillary-like structures with no supplementation of angiogenic factors; in the
      non-stimulated constructs, the cells formed sheets or aggregates. This chapter
      describes in detail the preparation method of the MNP-impregnated alginate
      scaffold, the cultivation setup for the cell construct under magnetic field
      conditions, and the set of analyses performed to characterize the resultant cell
      constructs.

PMID- 25070330
TI  - Shrink-induced biomimetic wrinkled substrates for functional cardiac cell
      alignment and culture.
AB  - The anisotropic alignment of cardiomyocytes in native myocardium tissue is a
      functional feature that is absent in traditional in vitro cardiac cell culture.
      Microenvironmental factors cue structural organization of the myocardium, which
      promotes the mechanical contractile properties and electrophysiological patterns
      seen in mature cardiomyocytes. Current nano- and microfabrication techniques,
      such as photolithography, generate simplified cell culture topographies that are
      not truly representative of the multifaceted and multi-scale fibrils of the
      cardiac extracellular matrix. In addition, such technologies are costly and
      require a clean room for fabrication. This chapter offers an easy, fast, robust,
      and inexpensive fabrication of biomimetic multi-scale wrinkled surfaces through
      the process of plasma treating and shrinking prestressed thermoplastic.
      Additionally, this chapter includes techniques for culturing stem cells and their
      cardiac derivatives on these substrates. Importantly, this wrinkled cell culture
      platform is compatible with both fluorescence and bright-field imaging; real-time
      physiological monitoring of CM action potential propagation and contraction
      properties can elucidate cardiotoxicity drug effects. 

PMID- 25070331
TI  - Injectable ECM scaffolds for cardiac repair.
AB  - Injectable biomaterials have been developed as potential minimally invasive
      therapies for treating myocardial infarction (MI) and heart failure. Christman et
      al. first showed that the injection of a biomaterial alone into rat myocardium
      can improve cardiac function after MI (Christman et al. Tissue Eng 10:403-409,
      2004). More recently, hydrogel forms of decellularized extracellular matrix (ECM)
      materials have shown substantial promise. Here we present the methods for
      fabricating an injectable cardiac specific ECM biomaterial shown to already have
      positive outcomes in small and large animal models for cardiac repair (Singelyn
      et al. Biomaterials 30:5409-5416, 2009; Singelyn et al. J Am Coll Cardiol 59:751
      763, 2012; Seif-Naraghi et al. Sci Transl Med 5:173ra25, 2013). Also covered are
      the methods for the injection of a biomaterial into rat myocardium using a
      surgical approach through the diaphragm. Although the methods shown here are for
      injection of an acellular biomaterial, cells or other therapeutics could also be
      added to the injection for testing other regenerative medicine strategies. 

PMID- 25070332
TI  - Generation of strip-format fibrin-based engineered heart tissue (EHT).
AB  - This protocol describes a method for casting fibrin-based engineered heart tissue
      (EHT) in standard 24-well culture dishes. In principle, a hydrogel tissue
      engineering method requires cardiomyocytes, a liquid matrix that forms a gel, a
      casting mold, and a device that keeps the developing tissue in place. This
      protocol refers to neonatal rat heart cells as the cell source; the matrix of
      choice is fibrin, and the tissues are generated in rectangular agarose-casting
      molds (12 * 3 * 3 mm) prepared in standard 24-well cell culture dishes, in which
      a pair of flexible silicone posts is suspended from above. A master mix of
      freshly isolated cells, medium, fibrinogen, and thrombin is pipetted into the
      casting mold and, over a period of 2 h, polymerizes and forms a fibrin cell block
      around two silicone posts. Silicone racks holding four pairs of silicone posts
      each are used to transfer the fresh fibrin cell blocks into new 24-well dishes
      with culture medium. Without further handling, the cells start to remodel the
      fibrin gel, form contacts with each other, elongate, and condense the gel to
      approximately 1/4 of the initial volume. Spontaneous and rhythmic contractions
      start after 1 week. EHTs are viable and relatively stable for several weeks in
      this format and can be subjected to repeated measurements of contractile function
      and final morphological and molecular analyses. 

PMID- 25070333
TI  - Cell tri-culture for cardiac vascularization.
AB  - Poor graft survival is a critical obstacle toward production of clinically
      relevant engineered tissues. Here we utilize a multicellular culturing approach
      for induction of vascular networks embedded within cardiac tissue constructs. The
      construct is composed of human cardiomyocytes, endothelial cells (ECs), and
      embryonic fibroblast cells co-seeded onto highly porous three-dimensional (3D)
      scaffolds. The resulting vascularized cardiac constructs showed microstructural
      details characteristic of cardiomyocytes and nascent vessels and exhibited
      synchronous beating activity in vitro. Upon implantation, stable grafts were
      formed presenting intense vascularization, with evidence of anastomosis between
      the pre-formed endothelial capillaries and host neovessels. 

PMID- 25070334
TI  - Cell sheet technology for cardiac tissue engineering.
AB  - In this chapter, we describe the methods for the fabrication and
      transfer/transplantation of 3D tissues by using cell sheet technology for cardiac
      tissue regeneration. A temperature-responsive culture surface can be fabricated
      by grafting a temperature-responsive polymer, poly(N-isopropylacrylamide), onto a
      polystyrene cell culture surface. Cells cultured confluently on such a culture
      surface can be recovered as an intact cell sheet, and functional three
      dimensional (3D) tissues can then be easily fabricated by layering the recovered
      cell sheets without any scaffolds or complicated manipulation. Cardiac cell
      sheets, myoblast sheets, mesenchymal stem cell sheets, cardiac progenitor cell
      sheets, etc., which are prepared from temperature-responsive culture surfaces,
      can be easily transplanted onto heart tissues of animal models, and those cell
      sheet constructs enhance the cell transplant efficiency, resulting in the
      induction of effective therapy. 

PMID- 25070335
TI  - Design and fabrication of biological wires.
AB  - Cardiac tissue engineering using human pluripotent stem cell-derived
      cardiomyocytes (hPSC-CMs) has facilitated the creation of in vitro diagnostic
      platforms to study novel small molecules and cardiac disease at the tissue level.
      Yet, due to the immaturity of hPSC-CMs, there is a low fidelity between tissue
      engineered cardiac tissues and adult cardiac tissues. To address this challenge,
      we have developed a platform that combines both physical and electrical cues to
      guide hPSC-CMs towards a more mature state in vitro. 

PMID- 25070336
TI  - Collagen-based engineered heart muscle.
AB  - Cardiac muscle engineering has evolved over nearly 20 years from a scientific
      oddity to a mainstream technology with a wide range of applications. Of the many
      published methods it appears that hydrogels constitute the preferred scaffolds
      for myocardial tissue engineering and support of organotypic development. Here we
      describe a simple and highly robust protocol for the generation of engineered
      heart muscle using a collagen-based hydrogel method. 

PMID- 25070337
TI  - Creation of a bioreactor for the application of variable amplitude mechanical
      stimulation of fibrin gel-based engineered cardiac tissue.
AB  - This chapter details the creation of three-dimensional fibrin hydrogels as an
      engineered myocardial tissue and introduces a mechanical stretch bioreactor
      system that allows for the cycle-to-cycle variable amplitude mechanical stretch
      of the constructs as a method of conditioning the constructs to be more similar
      to native tissue. Though mechanical stimulation has been established as a
      standard method of improving construct development, most studies have been
      performed under constant frequency and constant amplitude, even though
      variability is a critical aspect of healthy cardiac physiology. The introduction
      of variability in other organ systems has demonstrated beneficial effects to cell
      function in vitro. We hypothesize that the introduction of variability in
      engineered cardiac tissue could have a similar effect. 

PMID- 25070338
TI  - Preparation of acellular myocardial scaffolds with well-preserved cardiomyocyte
      lacunae, and method for applying mechanical and electrical simulation to tissue
      construct.
AB  - Cardiac tissue engineering/regeneration using decellularized myocardium has
      attracted great research attention due to its potential benefit for myocardial
      infarction (MI) treatment. Here we describe an optimal decellularization protocol
      to generate 3D porcine myocardial scaffolds with well-preserved cardiomyocyte
      lacunae and a multi-stimulation bioreactor that is able to provide coordinated
      mechanical and electrical stimulation for facilitating cardiac construct
      development. 

PMID- 25070339
TI  - Patch-clamp technique in ESC-derived cardiomyocytes.
AB  - ESC-derived cardiomyocytes are excitable cells that express many of the ion
      channels also found in adult cardiomyocytes. The patch-clamp technique is a
      powerful technique to characterize both the electrophysiological properties of
      excitable cells as well as the underlying ion channel currents responsible for
      these electrophysiological properties. The technique also allows rapid and
      accurate screening of the pharmacological actions of agents used to modulate
      cardiomyocyte properties. In this chapter we illustrate the use of the whole-cell
      patch clamp technique by recording hERG (human ether-a-go-go-related gene)
      currents and action potentials in ESC-derived cardiomyocytes and also examine the
      effects of hERG channel blocker, dofetilide. 

PMID- 25070340
TI  - Optogenetic control of cardiomyocytes via viral delivery.
AB  - Optogenetics is an emerging technology for the manipulation and control of
      excitable tissues, such as the brain and heart. As this technique requires the
      genetic modification of cells in order to inscribe light sensitivity, for cardiac
      applications, here we describe the process through which neonatal rat ventricular
      myocytes are virally infected in vitro with channelrhodopsin-2 (ChR2). We also
      describe in detail the procedure for quantitatively determining the optimal viral
      dosage, including instructions for patterning gene expression in multicellular
      cardiomyocyte preparations (cardiac syncytia) to simulate potential in vivo
      transgene distributions. Finally, we address optical actuation of ChR2-transduced
      cells and means to measure their functional response to light. 

PMID- 25070341
TI  - Methods for assessing the electromechanical integration of human pluripotent stem
      cell-derived cardiomyocyte grafts.
AB  - Cardiomyocytes derived from human pluripotent stem cells show tremendous promise
      for the replacement of myocardium and contractile function lost to infarction.
      However, until recently, no methods were available to directly determine whether
      these stem cell-derived grafts actually couple with host myocardium and fire
      synchronously following transplantation in either intact or injured hearts. To
      resolve this uncertainty, our group has developed techniques for the intravital
      imaging of hearts engrafted with stem cell-derived cardiomyocytes that have been
      modified to express the genetically encoded protein calcium sensor, GCaMP. When
      combined with the simultaneously recorded electrocardiogram, this protocol allows
      one to make quantitative assessments as to the presence and extent of host-graft
      electrical coupling as well as the timing and pattern of graft activation. As
      described here, this system has been employed to investigate the
      electromechanical integration of human embryonic stem cell-derived cardiomyocytes
      in a guinea pig model of cardiac injury, but analogous approaches should be
      applicable to other human graft cell types and animal models. 

PMID- 25070342
TI  - Quantifying electrical interactions between cardiomyocytes and other cells in
      micropatterned cell pairs.
AB  - Micropatterning is a powerful technique to control cell shape and position on a
      culture substrate. In this chapter, we describe the method to reproducibly create
      large numbers of micropatterned heterotypic cell pairs with defined size, shape,
      and length of cell-cell contact. These cell pairs can be utilized in patch clamp
      recordings to quantify electrical interactions between cardiomyocytes and non
      cardiomyocytes. 

PMID- 25070345
TI  - Serological responses to prednisolone treatment in leprosy reactions: study of
      TNF-alpha, antibodies to phenolic glycolipid-1, lipoarabinomanan, ceramide and
      S100-B.
AB  - BACKGROUND: Corticosteroids have been extensively used in the treatment of
      immunological reactions and neuritis in leprosy. The present study evaluates the
      serological response to steroid treatment in leprosy reactions and neuritis.
      METHODS: Seven serological markers [TNF-alpha, antibodies to Phenolic glycolipid
      1 (PGL-1 IgM and IgG), Lipoarabinomannan (LAM IgG1 and IgG3), C2-Ceramide and
      S100 B] were analyzed longitudinally in 72 leprosy patients before, during and
      after the reaction. At the onset of reaction these patients received a standard
      course of prednisolone. The levels of the above markers were measured by Enzyme
      linked immunosorbent assay (ELISA) and compared with the individuals own value in
      the month prior to the reaction and presented as percentage increase. RESULTS:
      One month before the reaction individuals showed a varying increase in the level
      of different markers such as TNF-alpha (53%) and antibodies to Ceramide (53%),
      followed by to PGL-1 (51%), S100B (50%) and LAM (26%). The increase was
      significantly associated with clinical finding of nerve pain, tenderness and new
      nerve function impairment. After one month prednisolone therapy, there was a fall
      in the levels [TNF-alpha (60%), C2-Ceramide (54%), S100B (67%), PGL-1(47%) and
      LAM (52%)] with each marker responding differently to steroid. CONCLUSION:
      Reactions in leprosy are inflammatory processes wherein a rise in set of
      serological markers can be detected a month before the clinical onset of
      reaction, some of which remain elevated during their action and steroid treatment
      induces a variable fall in the levels, and this forms the basis for a variable
      individual response to steroid therapy.

PMID- 25070343
TI  - Antitumor mechanisms of S-allyl mercaptocysteine for breast cancer therapy.
AB  - BACKGROUND: S-allyl mercaptocysteine (SAMC), a water-soluble component derived
      from garlic, has been found to exert multi-antitumor activities. This study was
      to investigate the responsible molecular mechanisms of SAMC in human breast
      cancer cell lines. METHODS: Sulforhodamine B assay was used to determine cell
      viability, flow cytometry was applied for the analysis of cell cycle and cell
      apoptosis, the change of protein was detected by Western blot. RESULTS: It was
      found that SAMC exhibited an effective cell growth inhibition of human breast
      cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative) in a dose- and
      time-dependent manner by inducing cell cycle arrested in G0/G1 phase, the block
      of cell cycle was associated with the up-regulation of p53 and p21. Furthermore,
      the SAMC-mediated cell cycle arrest was accompanied with promotion of apoptosis,
      as indicated by the changes in the nuclear morphology and expressions of
      apoptosis-related proteins. SAMC clearly triggered the mitochondrial apoptotic
      pathway as indicated by activation of Bax, decreased expression of Bcl-2 and Bcl
      XL, and subsequent activation of caspase-9 and caspase-3. CONCLUSION: These
      results highlight the value of a continued investigation into the use of SAMC as
      a potential antitumor candidate for breast cancer.

PMID- 25070347
TI  - Effects of exercise on central aortic pressure before and after treatment with
      renin-angiotensin system blockade in patients with hypertension.
AB  - INTRODUCTION: Brachial blood pressure increases with exercise and an excessive
      rise predicts increased cardiovascular risk. Measurement of brachial blood
      pressure alone may exaggerate the true blood pressure elevation due to exercise
      induced change to pressure amplification. Whether blood pressure-lowering
      treatment modulates pressure amplification during exercise is unknown. METHODS:
      Thirty-two participants with stage 1-2 hypertension (mean age 59.2 years)
      received eight weeks' blood pressure lowering with either aliskiren (300mg, n=16)
      or valsartan (320mg, n=16). Brachial and central aortic pressure (CASP) were
      measured non-invasively during treadmill exercise (Bruce protocol) at baseline,
      after eight weeks' treatment and 48 hours following treatment withdrawal.
      RESULTS: The rise in brachial blood pressure with exercise exceeded the rise in
      CASP, indicative of enhanced pressure amplification. Eight weeks' treatment
      elicited similar reductions in brachial blood pressure and CASP which did not
      differ between rest and peak exercise (p>0.05). The exercise-induced increase in
      systolic pressure amplification did not differ between baseline and following
      eight weeks' treatment (p>0.05). These effects remained unchanged following
      treatment withdrawal. CONCLUSION: Blood pressure lowering does not directly
      influence the relationship between aortic and brachial pressure either at rest or
      during exercise in patients with hypertension, other than through proportionate
      lowering of both pressures. These effects remained unchanged 48 hours after a
      simulated missed medication dose.

PMID- 25070346
TI  - The effectiveness of riboflavin photochemical-mediated virus inactivation and
      changes in protein retention in fresh-frozen plasma treated using a flow-based
      treatment device.
AB  - BACKGROUND: A flow-based treatment device using riboflavin and ultraviolet (UV)
      light was developed to inactivate viruses in fresh-frozen plasma (FFP). The
      objective of this study was to evaluate the in vitro effectiveness of virus
      inactivation and changes in protein quality in FFP treated with this device.
      STUDY DESIGN AND METHODS: FFP-contaminating viruses were treated with riboflavin
      and UV light using a one-pass linear flow device. The infectivity of viruses was
      measured using established biologic assays. Real-time polymerase chain reaction
      (PCR) was performed to detect damage to viral nucleotides after treatment.
      Treated plasma was analyzed using standard coagulation assays. RESULTS: FFP
      treated at the UV dose of 3.6 J/cm(2) (J) exhibited a mean reduction of virus
      titer of more than 4 logs. The effectiveness increased significantly at higher
      doses. Real-time PCR showed that the cycle threshold values for both complete
      inactivation and virus recultivation were higher than that of the untreated
      sample. At doses of 3.6, 5.4, and 7.2 J, the protein recovery rates were 60.2 +/-
      8.6, 46.6 +/- 9.4, and 28.0 +/- 1.0% for fibrinogen; 67.0 +/- 3.1, 57.3 +/- 8.0,
      and 49.2 +/- 3.8% for Factor VIII; 93.6 +/- 2.8, 89.6 +/- 6.1, and 86.5 +/- 5.3%
      for antithrombin-III; and 72.1 +/- 5.6, 59.8 +/- 14.2, and 49.2 +/- 8.4% for
      Protein C, respectively. CONCLUSION: The effectiveness of virus inactivation was
      enhanced, but total activity of plasma factors was reduced, in a UV dose
      dependent manner.

PMID- 25070348
TI  - Effects of angiotensin II receptor blockade on cerebral, cardiovascular, counter
      regulatory, and symptomatic responses during hypoglycaemia in patients with type
      1 diabetes.
AB  - INTRODUCTION: High spontaneous activity of the renin-angiotensin system (RAS)
      results in more pronounced cognitive impairment and more prolonged QTc interval
      during hypoglycaemia in type 1 diabetes. We tested whether angiotensin II
      receptor blockade improves cerebral and cardiovascular function during
      hypoglycaemia. METHODS: Nine patients with type 1 diabetes and high spontaneous
      RAS activity were included in a double-blind, randomised, cross-over study on the
      effect of angiotensin II receptor antagonist (candesartan 32 mg) or placebo for
      one week on cognitive function, cardiovascular parameters, hormonal counter
      regulatory response, substrate mobilisation, and symptoms during hypoglycaemia
      induced by two hyperinsulinaemic, hypoglycaemic clamps. RESULTS: Compared to
      placebo, candesartan did neither change performance of the cognitive tests nor
      the EEG at a plasma glucose concentration of 2.6+/-0.2 mmol/l. During candesartan
      treatment, the QT interval in the ECG was not affected. No effect of candesartan
      was observed in the hormonal counter-regulatory responses, in substrate
      concentrations, or in symptom scores. A 36% reduced glucose infusion rate during
      hypoglycaemia with candesartan was observed. CONCLUSION: In conclusion
      candesartan has no effect on cerebral function during mild experimental
      hypoglycaemia in subjects with type 1 diabetes and high RAS activity. Candesartan
      may reduce glucose utilisation or increase endogenous glucose production during
      hypoglycaemia.

PMID- 25070349
TI  - Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration.
AB  - BACKGROUND: In the present study, we investigated the potential effect of
      aliskiren on smooth muscle cell (SMC) migration in response to prorenin. METHODS:
      Cultured human SMCs were incubated with angiotensinogen (ANG) (1.5 * 10(-7)M) and
      increasing concentrations of aliskiren (10(-6)-10(-5)M). After 24 h, SMC
      migration was assessed by Boyden's chamber chemotactic assay using prorenin as
      chemotactic factor (10(-8)M). The effect of aliskiren on RhoA and Rac activity
      was also determined by G-LISA assay and the lamellipodia formation by rhodamine
      phalloidin staining. Changes in cell morphology were recorded in real-time using
      the iCelligence system. RESULTS: Aliskiren determined, at 10(-5)M, a significant
      inhibition of SMC migration induced by prorenin (-66.4 +/- 18.1%; p < 0.05),
      while no significant effect was observed when PDGF-BB was utilized as chemotactic
      agent. Aliskiren also reduced Rac-GTP levels in response to prorenin (-54.2 +/-
      5.4%) without affecting the RhoA-GTP levels. Finally, aliskiren inhibited both
      the lamellipodia formation and morphological changes induced by prorenin with no
      significant effect on PDGF-BB activity. CONCLUSIONS: Taken together, we provide
      the first evidence of the inhibitory action of aliskiren on SMC migration induced
      by prorenin.

PMID- 25070350
TI  - Combination therapy with aliskiren versus ramipril or losartan added to
      conventional therapy in patients with type 2 diabetes mellitus, uncontrolled
      hypertension and microalbuminuria.
AB  - HYPOTHESIS/INTRODUCTION: The aim of this study was to assess the antihypertensive
      efficacy and safety of aliskiren versus ramipril or losartan in hypertensive
      patients with type 2 diabetes mellitus, microalbuminuria and uncontrolled
      hypertension, despite the use of optimal conventional antihypertensive therapy.
      MATERIALS AND METHODS: In this open-label active comparator study, 126 patients
      were randomly assigned to receive 24 weeks of additional therapy with aliskiren
      (Group A) or either losartan or ramipril (Group B), according to whether a
      patient was already treated with an angiotensin-converting enzyme inhibitor or an
      angiotensin receptor blocker, respectively. RESULTS: After 24 weeks, both
      treatment groups experienced a significant reduction of systolic blood pressure (
      11.37% and -8.47%, respectively; both p <0.001 vs. baseline) and diastolic blood
      pressure levels (-10.67% and -9.28%, respectively; both p <0.001 vs. baseline),
      with a greater reduction of mean systolic values in Group A compared with Group B
      (p <0.001). Furthermore, after six months microalbuminuria was significantly
      decreased in both treatment groups (-67.62% and -49.1%, respectively; both p
      <0.001), with a reduction rate in Group A significantly higher than in Group B
      (p<0.001). CONCLUSIONS: The addition of aliskiren to optimal conventional therapy
      provided a higher reduction of blood pressure and urinary albumin excretion when
      compared with the addition of losartan or ramipril.

PMID- 25070351
TI  - Association between angiotensin-converting enzyme gene insertion/deletion
      polymorphism and pancreatitis risk: A meta-analysis.
AB  - OBJECTIVE: Many studies have focused on the relationship between the angiotensin
      converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism and
      pancreatitis risk, but the results remain inconsistent. Thus, a meta-analysis was
      carried out to derive a more precise estimation of the association between ACE
      I/D polymorphism and pancreatitis risk. METHODS: Relevant publications were
      searched in several widely used databases and seven studies from six eligible
      articles were included in the meta-analysis. Pooled odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated to evaluate the strength of the
      association between ACE I/D polymorphism and pancreatitis risk. RESULTS:
      Significant associations between ACE I/D polymorphism and pancreatitis risk were
      observed in both overall meta-analysis for DI versus II (OR=0.80, 95% CI=0.67
      0.96) and DD + DI versus II (OR=0.83, 95% CI=0.70-0.98), and acute pancreatitis
      subgroup for DI versus II (OR=0.65, 95% CI=0.44-0.95). However, no significant
      pancreatitis risk variation was detected for all genetic models in the subgroup
      meta-analysis based on ethnicity. CONCLUSIONS: According to the results of our
      meta-analysis, the ACE I/D polymorphism probably associates with pancreatitis
      risk, especially acute pancreatitis risk, with the I allele acting as a risk
      factor.

PMID- 25070352
TI  - ACE2 activity was increased in atherosclerotic plaque by losartan: Possible
      relation to anti-atherosclerosis.
AB  - INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin
      angiotensin system (RAS) and it has been proposed that ACE2 is a potential
      therapeutic target for the control of cardiovascular disease. The effect of
      losartan on the ACE2 activity in atherosclerosis was studied. METHODS:
      Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet
      for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d)
      was given for 3 months. ACE2 activity was measured by fluorescence assay and the
      extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In
      addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs)
      in vitro was also evaluated. RESULTS: Losartan increased ACE2 activity in
      atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic
      evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2
      activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with
      PD98059 prevented Ang II-induced down-regulation of ACE2 activity. CONCLUSIONS:
      The results showed that ACE2 activity was regulated in atherosclerotic plaque by
      losartan, which may play an important role in treatment of atherosclerosis. The
      mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs
      (MAPKs) signaling pathway.

PMID- 25070353
TI  - The power comparison of the haplotype-based collapsing tests and the variant
      based collapsing tests for detecting rare variants in pedigrees.
AB  - BACKGROUND: Both common and rare genetic variants have been shown to contribute
      to the etiology of complex diseases. Recent genome-wide association studies
      (GWAS) have successfully investigated how common variants contribute to the
      genetic factors associated with common human diseases. However, understanding the
      impact of rare variants, which are abundant in the human population (one in every
      17 bases), remains challenging. A number of statistical tests have been developed
      to analyze collapsed rare variants identified by association tests. Here, we
      propose a haplotype-based approach. This work inspired by an existing statistical
      framework of the pedigree disequilibrium test (PDT), which uses genetic data to
      assess the effects of variants in general pedigrees. We aim to compare the
      performance between the haplotype-based approach and the rare variant-based
      approach for detecting rare causal variants in pedigrees. RESULTS: Extensive
      simulations in the sequencing setting were carried out to evaluate and compare
      the haplotype-based approach with the rare variant methods that drew on a more
      conventional collapsing strategy. As assessed through a variety of scenarios, the
      haplotype-based pedigree tests had enhanced statistical power compared with the
      rare variants based pedigree tests when the disease of interest was mainly caused
      by rare haplotypes (with multiple rare alleles), and vice versa when disease was
      caused by rare variants acting independently. For most of other situations when
      disease was caused both by haplotypes with multiple rare alleles and by rare
      variants with similar effects, these two approaches provided similar power in
      testing for association. CONCLUSIONS: The haplotype-based approach was designed
      to assess the role of rare and potentially causal haplotypes. The proposed rare
      variants-based pedigree tests were designed to assess the role of rare and
      potentially causal variants. This study clearly documented the situations under
      which either method performs better than the other. All tests have been
      implemented in a software, which was submitted to the Comprehensive R Archive
      Network (CRAN) for general use as a computer program named rvHPDT.

PMID- 25070355
TI  - Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic
      epithelial cells that emerge in the postnatal thymus.
AB  - Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively)
      provide inductive microenvironments for T-cell development and selection. The
      differentiation pathway of cTEC/mTEC lineages downstream of common bipotent
      progenitors at discrete stages of development remains unresolved. Using IL
      7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that
      the stepwise acquisition of chemokine (C-C motif) receptor-like 1 (CCRL1) is a
      late determinant of cTEC differentiation. Although cTECs expressing high CCRL1
      levels (CCRL1(hi) ) develop normally in immunocompetent and Rag2(-/-) thymi,
      their differentiation is partially blocked in Rag2(-/-) Il2rg(-/-) counterparts.
      These results unravel a novel checkpoint in cTEC maturation that is regulated by
      the cross-talk between TECs and immature thymocytes. Additionally, we identify
      new Ulex europaeus agglutinin 1 (UEA)(+) mTEC subtypes expressing intermediate
      CCRL1 levels (CCRL1(int) ) that conspicuously emerge in the postnatal thymus and
      differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in
      Rag2(-/-) thymi, CCRL1(int) mTECs are restored in Rag2(-/-) Marilyn TCR-Tg mice,
      indicating that the appearance of postnatal-restricted mTECs is closely linked
      with T-cell selection. Our findings suggest that alternative temporally
      restricted routes of new mTEC differentiation contribute to the establishment of
      the medullary niche in the postnatal thymus. 

PMID- 25070354
TI  - Crucial role of PA in virus life cycle and host adaptation of influenza A virus.
AB  - The PA protein is the third subunit of the polymerase complex of influenza A
      virus. Compared with the other two polymerase subunits (PB2 and PB1), its precise
      functions are less defined. However, in recent years, advances in protein
      expression and crystallization technologies and also the reverse genetics,
      greatly accelerate our understanding of the essential role of PA in virus
      infection. Here, we first review the current literature on this remarkably
      multifunctional viral protein regarding virus life cycle, including viral RNA
      transcription and replication, viral genome packaging and assembly. We then
      discuss the various roles of PA in host adaption in avian species and mammals,
      general virus-host interaction, and host protein synthesis shutoff. We also
      review the recent findings about the novel proteins derived from PA. Finally, we
      discuss the prospects of PA as a target for the development of new antiviral
      approaches and drugs. 

PMID- 25070356
TI  - Selective detection of endogenous H2S in living cells and the mouse hippocampus
      using a ratiometric fluorescent probe.
AB  - As one of three gasotransmitters, the fundamental signalling roles of hydrogen
      sulphide are receiving increasing attention. New tools for the accurate detection
      of hydrogen sulphide in cells and tissues are in demand to probe its biological
      functions. We report the p-nitrobenzyl-based ratiometric fluorescent probe RHP-2,
      which features a low detection limit, high selectivity and good photostability.
      The emission intensity ratios had a good linear relationship with the sulphide
      concentrations in PBS buffer and bovine serum. Our probe was applied to the
      ratiometric determination and imaging of endogenous H2S in living cells.
      Furthermore, RHP-2 was used as an effective tool to measure endogenous H2S in the
      mouse hippocampus. We observed a significant reduction in sulphide concentrations
      and downregulated expression of cystathionine beta-synthetase (CBS) mRNA and CBS
      protein in the mouse hippocampus in a chronic unpredictable mild stress (CUMS)
      induced depression model. These data suggested that decreased concentrations of
      endogenous H2S may be involved in the pathogenesis of chronic stress depression. 

PMID- 25070357
TI  - Publication of pivotal efficacy trials for novel therapeutic agents approved
      between 2005 and 2011: a cross-sectional study.

PMID- 25070358
TI  - Evolving therapeutic concepts in prostate cancer based on genome-wide analyses
      (review).
AB  - Treatment of castration resistant prostate cancer (CRPC) continues to represent a
      major urooncological challenge due to tumor heterogeneity and the inevitable
      development of therapy resistance. Although androgen deprivation therapy retains
      an important role in the management of CRPC, recent evidence suggests that a
      broader spectrum of therapeutic targets may improve patient response and delay
      development of advanced disease. Genome-wide analyses have identified four major
      signaling nodes that are most frequently altered in prostate cancer: i) the
      androgen receptor (AR); ii) the PI3K pathway; iii) the Ras/Raf/MEK/ERK pathway;
      and iv) the retinoblastoma protein (pRB) signaling pathway. Extensive crosstalk
      and redundancy exists between these signaling pathways, which underscores the
      need for combination therapies. There are several novel AR pathway inhibitors
      currently in clinical use. Clinical trials are being performed on single-agent
      PI3K inhibitors with some success in tumors with genetically altered PI3K
      components. MEK/ERK inhibitors are also in clinical trials and the importance of
      pRB inactivation in prostate cancer is becoming more widely recognized. A greater
      understanding of the effects of single agent therapy on compensatory signaling
      pathway activation that can potentially thwart antitumoral responses is urgently
      needed and will provide additional insight into the mechanism of therapy
      resistance and how to further delay the progression to lethal disease. 

PMID- 25070359
TI  - Emotional variability in mother-adolescent conflict interactions and
      internalizing problems of mothers and adolescents: dyadic and individual
      processes.
AB  - Emotional variability reflects the ability to flexibly switch among a broad range
      of positive and negative emotions from moment-to-moment during interactions.
      Emotional variability during mother-adolescent conflict interactions is
      considered to be important for healthy socio-emotional functioning of mothers and
      adolescents. The current observational study examined whether dyadic emotional
      variability, maternal emotional variability, and adolescent emotional variability
      during conflict interactions in early adolescence predicted mothers' and
      adolescents' internalizing problems five years later. We used data from 92 mother
      adolescent dyads (Mage T1 = 13.05; 65.20 % boys) who were videotaped at T1 while
      discussing a conflict. Emotional variability was derived from these conflict
      interactions and it was observed for mother-adolescent dyads, mothers and
      adolescents separately. Mothers and adolescents also completed questionnaires in
      early adolescence (T1) and five years later in late adolescence (T6) on mothers'
      internalizing problems, and adolescents' anxiety and depressive symptoms.
      Hierarchical regression analyses showed that less dyadic emotional variability in
      early adolescence predicted relative increases in mothers' internalizing
      problems, adolescents' depressive symptoms, and adolescents' anxiety symptoms
      from early to late adolescence. Less maternal emotional variability only
      predicted relative increases in adolescents' anxiety symptoms over time. The
      emotional valence (e.g., types of emotions expressed) of conflict interactions
      did not moderate the results. Taken together, findings highlighted the importance
      of considering limited emotional variability during conflict interactions in the
      development, prevention, and treatment of internalizing problems of mothers and
      adolescents.

PMID- 25070360
TI  - Dynamics of positive emotion regulation: associations with youth depressive
      symptoms.
AB  - Depression is frequently considered a disorder of impaired affect regulation with
      deficits across both positive and negative affective systems. However, where
      deficits in emotion regulation occur in youth, specifically regarding regulation
      of positive emotions, is relatively unknown. The current study tested whether
      deficits in broad (felt and expressed) and specific (up-regulation and
      maintenance) positive emotion processes are associated with youth depressive
      symptoms. Adolescents (n = 134; 65 girls) in grades 7 to 9 completed a self
      report measure of depressive symptoms prior to participating in two parent-child
      interactions tasks, a rewarding trivia task and a problem-solving conflict task.
      During the interaction tasks, adolescent's overall self-reported experience and
      observed expression of positive affect (PA) was examined. Following the reward
      task, youth's ability to up-regulate PA (PA response) and maintain PA while
      buffering against NA (PA persistence) was explored observationally. Results
      suggested that reduced experience and expression of PA was associated with
      depression symptoms, but only in a context that elicited negative emotions. No
      association was found between PA response and depression symptoms; however,
      shorter PA persistence was associated with elevated depressive symptoms. Youth
      higher in depressive symptoms appear able to respond similarly to rewarding
      events, but fail to maintain PA and ward off NA when transitioning from a
      positive to negative task. 

PMID- 25070361
TI  - Mesenchymal stem cells suppress CD8+ T cell-mediated activation by suppressing
      natural killer group 2, member D protein receptor expression and secretion of
      prostaglandin E2, indoleamine 2, 3-dioxygenase and transforming growth factor
      beta.
AB  - Bone marrow mesenchymal stem cells (BMSCs) inhibit immune cell responsiveness,
      and especially of T lymphocytes. We showed that BMSCs markedly inhibited the
      proliferation and cytokine production by CD8(+) T cells by a cell-to-cell contact
      phenomenon and secretion of soluble factors. BMSCs down-regulate the expression
      of natural killer group 2, member D protein (NKG2D) receptors on CD8(+) T cells
      when co-cultured with them. Moreover, CD8(+) T cells that express low levels of
      NKG2D had impaired proliferation after triggering by a mitogen. The major
      histocompatibility complex (MHC) class I chain-related (MIC) A/B molecule, which
      is a typical ligand for NKG2D, was expressed on BMSCs, and caused dampening of
      cell proliferation. Monoclonal antibody blocking experiments targeted to MIC A/B
      impaired CD8(+) T cell function, as evaluated by proliferation and cytokine
      production. In addition, the production of prostaglandin E2 (PGE2 ), indoleamine
      2, 3-dioxygenase (IDO) and transforming growth factor (TGF)-beta1 were increased
      when BMSCs were co-cultured with CD8(+) T cells. The addition of specific
      inhibitors against PGE2 , IDO and TGF-beta partially restored the proliferation
      of CD8(+) T cells. Our results suggest that BMSCs suppress CD8(+) T cell-mediated
      activation by suppressing NKG2D expression and secretion of PGE2, IDO and TGF
      beta. Our observations further confirm the feasibility of BMSCs as a potential
      adoptive cellular therapy in immune-mediated diseases such as graft-versus-host
      disease (GVHD).

PMID- 25070362
TI  - The first skin cancer screening day at the Italian parliament: a Euromelanoma
      initiative.
AB  - BACKGROUND: The effort to decrease incidence/mortality of skin cancer should
      target not only the general public but also politicians and decision makers, to
      create a proper health policy. We report the results of the first Skin Cancer
      Screening Day at the Italian Parliament, organized to draw politicians' attention
      on skin cancer. METHODS: A questionnaire was used to collect data on
      participants' characteristics and suspected skin cancers. RESULTS: We screened 70
      members of parliament (61.4% males, median age 54 years). Overall skin cancer
      suspicion rate was 14.5%. Suspicion rate, detection rate, and positive predictive
      values for melanoma were respectively 1.6, 1.6, and 100%, and for basal cell
      carcinoma 6.5, 1.6, and 25%. Highly educated, <54-year-old females reported sun
      seeking behaviors. CONCLUSIONS: The considerable suspicion rate produced by this
      screening is justified by the particular demographics of the study population.
      Italian members of parliament display sun-seeking behaviors similar to those
      previously described in the general public. Increasing politicians' attention on
      skin cancer is vital for sufficient resources to be allocated to prevention
      strategies. Expert medical groups and politicians should cooperate to create a
      proper, integrated policy on skin cancer.

PMID- 25070363
TI  - The effects of feeder design and dietary dried distillers' grains with solubles
      on the performance and carcass characteristics of finishing pigs.
AB  - Three experiments were conducted to compare the effects of a conventional dry
      (five 30.5-cm spaces 152.4 cm wide; Staco Inc., Schaefferstown, PA) vs. a wet-dry
      (double sided; each side = 38.1-cm space; Crystal Spring; GroMaster Inc., Omaha,
      NE) finishing feeder (Exp. 1 and 2) and to evaluate the effects of feeder design
      and dietary level of dried distillers' grains with solubles (DDGS; >10% oil; Exp.
      3) on performance and carcass characteristics of finishing pigs. In Exp. 1, 1,186
      pigs (32.1 kg BW) were used in a 69-d experiment. There were 26 to 28 pigs per
      pen and 22 pens per feeder design, and all pigs received the same diets in 4
      phases. In Exp. 2, 1,236 pigs (28.7 kg BW) were used in a 104-d experiment, with
      25 to 28 pigs per pen and 23 pens per feeder design, and all pigs received the
      same diets in 5 phases. Carcass measurements were obtained from 11 pens of each
      feeder design after harvest. In Exp. 3, 1,080 pigs (35.1 kg BW) were used in a 99
      d 2 * 2 factorial with main effects of feeder design (dry vs. wet-dry feeders)
      and DDGS (20 vs. 60%) with 10 pens of 27 pigs per treatment and all diets fed in
      4 phases. Jowl fat samples were collected from 2 pigs per pen for fatty acid
      analysis and iodine value (IV) determination. In all experiments, pigs fed with
      the wet-dry feeder had greater (P < 0.05) ADG, ADFI, and final BW. In Exp. 2 and
      3, HCW and backfat depth were increased (P < 0.05) for pigs fed with a wet-dry
      feeder, but G:F and fat-free lean index (FFLI) were reduced. Jowl IV was also
      reduced (P < 0.05) with a wet-dry feeder in Exp. 3. Pigs fed 60% DDGS in Exp. 3
      had decreased (P < 0.05) ADG, G:F, final BW, HCW, and backfat but increased jowl
      IV and a tendency (P < 0.07) toward greater FFLI regardless of feeder type. In
      conclusion, pigs fed with this specific type of wet-dry feeder had improved ADG
      and ADFI, poorer G:F, and increased backfat depth compared to pigs fed with a
      conventional dry feeder. The poorer growth performance and increased jowl IV of
      pigs fed diets with 60% DDGS was similarly exhibited for pigs fed on both
      feeders. 

PMID- 25070364
TI  - The effects of low-, medium-, and high-oil distillers dried grains with solubles
      on growth performance, nutrient digestibility, and fat quality in finishing pigs.
AB  - A total of 1,480 pigs were used in 3 experiments to determine the effects of corn
      distillers dried grains with solubles (DDGS) varying in oil content on growth
      performance, carcass traits, and nutrient digestibility in finishing pigs. In
      Exp. 1, 1,198 pigs (PIC Line 337 * 1050; initially 46.1 kg) were allotted to a
      corn-soybean meal-based diet or diets with 20 or 40% of a 5.4% oil DDGS (29.5%
      CP, 8.9% ADF, and 21.8% NDF; as-fed basis) or a 9.6% oil DDGS (29.6% CP, 15.3%
      ADF, and 28.6% NDF; as-fed basis). From d 0 to 82, ADG was unaffected by DDGS
      source or level. However, increasing 5.4% oil DDGS decreased (linear, P < 0.01)
      G:F, whereas G:F did not change among pigs fed 9.6% oil DDGS (DDGS source * level
      interaction; P < 0.01). Regardless of DDGS source, carcass yield and HCW
      decreased (linear, P < 0.04) with increasing DDGS. Increasing DDGS increased jowl
      iodine value (IV), but the magnitude was greater in pigs fed the 9.6% oil DDGS
      compared with those fed 5.4% oil DDGS (DDGS source * level interaction; P <
      0.01). In Exp. 2, 270 pigs (PIC Line 327 * 1050; initially 46.5 kg) were allotted
      a corn-soybean meal-based diet or diets with 20 or 40% of a 9.4% oil DDGS (29.4%
      CP, 19.6% ADF, and 34.5% NDF; as-fed basis) or a 12.1% oil DDGS (28.5% CP, 17.6%
      ADF, and 31.4% NDF; as-fed basis). From d 0 to 75, ADG increased and then
      decreased for pigs fed 9.4% oil DDGS but was unchanged for pigs fed 12.1% oil
      DDGS (quadratic interaction, P < 0.02). Increasing DDGS increased (linear, P <
      0.01) jowl IV and tended (linear, P < 0.07) to increase G:F. Regardless of
      source, HCW and carcass yield decreased (linear, P < 0.05) as DDGS increased. In
      Exp. 3, nutrient digestibility of the 4 DDGS sources was determined using pigs
      fed either a corn-based basal diet (96.6% corn and 3.4% vitamins and minerals) or
      a DDGS diet with 50% basal diet and 50% DDGS. On an as-fed basis, corn contained
      3,871 and 3,515 kcal/kg GE and DE, respectively. The 5.4, 9.6, 9.4, and 12.1% oil
      DDGS contained 4,347, 4,648, 4,723, and 4,904 kcal/kg (as-fed basis) GE and
      3,417, 3,690, 3,838, and 3,734 kcal/kg DE, respectively (as-fed basis). Stepwise
      regression indicated that the oil (ether extract) content was the only
      significant variable to explain differences in energy content. The equations
      generated to predict DE and NE as a function of oil content on an as-fed basis
      were DE (kcal/kg) = 62.347 * ether extract (%) + 3,058.13 (n = 5, adjusted R(2) =
      0.41) and NE (kcal/kg) = 115.011 * ether extract (%) + 1,501.01 (n = 5, adjusted
      R(2) = 0.86). 

PMID- 25070365
TI  - Isoflavones of the soybean components and the effect of germination time in the
      cotyledons and embryonic axis.
AB  - The aim of this study was to evaluate the content of different forms of
      isoflavones of BRS 284 soybean components and the effect of germination time in
      the cotyledons, radicle, and hypocotyl. Seeds were germinated until 168 h at 35 
      degrees C and collected each 24 h. The isoflavone content was determined by
      ultraperformance liquid chromatography, and the data were subjected to regression
      analysis. In cotyledons, germination time had a quadratic effect on daidzin and
      genistin contents and a linear effect on malonyldaidzin and malonylgenistin
      contents. In radicles, germination time had a quadratic effect on daidzin,
      glycitin, malonylgenistin, and malonylglycitin contents in addition to a linear
      effect on malonyldaidzin content. In hypocotyls, germination time showed a cubic
      effect on daidzin and genistin contents, a quadratic effect on malonyldaidzin,
      malonylgenistin, and malonylglycitin contents, and a linear effect on genistein
      content; glycitin, daidzein and glycitein were detected in a few germination
      times. 

PMID- 25070366
TI  - Association between pain, central sensitization and anxiety in postherpetic
      neuralgia.
AB  - BACKGROUND: In postherpetic neuralgia (PHN), dorsal root ganglia neurons are
      damaged. According to the proposed models, PHN pain might be associated with
      nociceptive deafferentation, and peripheral (heat hyperalgesia) or central
      sensitization (allodynia). METHODS: In 36 PHN patients, afferent nerve fibre
      function was characterized using quantitative sensory testing and histamine
      induced flare analysis. Psychological factors were evaluated with the Hospital
      Anxiety and Depression Scale (HADS), disease-related quality of life (QoL) with
      SF-36 and pain with the McGill questionnaire [pain rating index (PRI)]. The
      patients were also divided into subgroups according to the presence or absence of
      brush-evoked allodynia as a sign of central sensitization. RESULTS: For all
      patients, warm, cold and mechanical detection was impaired (p < 0.001 each) and
      the size of the histamine flare was diminished on the affected side (p < 0.05);
      pain thresholds with the exception of brush-evoked allodynia (p < 0.05) were
      unaltered. Correlation analysis revealed allodynia, anxiety, depression, QoL and
      age as relevant factors associated with pain severity (PRI). Allodynia was
      present in 23 patients (64%). In these patients, heat pain perception was
      preserved; the histamine flare was larger; the pinprick pain was increased as
      were McGill PRI sensory subscore, actual pain rating and almost significantly
      pain (McGill PRI) over the last 4 weeks. CONCLUSIONS: PHN is associated with
      damage of afferent fibres. Central sensitization (i.e., allodynia) might
      contribute to PHN pain. There was a striking association between anxiety,
      depression and age, and the magnitude of PHN pain.

PMID- 25070367
TI  - A novel platform for engineering blood-brain barrier-crossing bispecific
      biologics.
AB  - The blood-brain barrier (BBB) prevents the access of therapeutic antibodies to
      central nervous system (CNS) targets. The engineering of bispecific antibodies in
      which a therapeutic "arm" is combined with a BBB-transcytosing arm can
      significantly enhance their brain delivery. The BBB-permeable single-domain
      antibody FC5 was previously isolated by phenotypic panning of a naive llama
      single-domain antibody phage display library. In this study, FC5 was engineered
      as a mono- and bivalent fusion with the human Fc domain to optimize it as a
      modular brain delivery platform. In vitro studies demonstrated that the bivalent
      fusion of FC5 with Fc increased the rate of transcytosis (Papp) across brain
      endothelial monolayer by 25% compared with monovalent fusion. Up to a 30-fold
      enhanced apparent brain exposure (derived from serum and cerebrospinal fluid
      pharmacokinetic profiles) of FC5- compared with control domain antibody-Fc
      fusions after systemic dosing in rats was observed. Systemic pharmacological
      potency was evaluated in the Hargreaves model of inflammatory pain using the BBB
      impermeable neuropeptides dalargin and neuropeptide Y chemically conjugated with
      FC5-Fc fusion proteins. Improved serum pharmacokinetics of Fc-fused FC5
      contributed to a 60-fold increase in pharmacological potency compared with the
      single-domain version of FC5; bivalent and monovalent FC5 fusions with Fc
      exhibited similar systemic pharmacological potency. The study demonstrates that
      modular incorporation of FC5 as the BBB-carrier arm in bispecific antibodies or
      antibody-drug conjugates offers an avenue to develop pharmacologically active
      biotherapeutics for CNS indications.

PMID- 25070368
TI  - AMSH-mediated deubiquitination of Cx43 regulates internalization and degradation
      of gap junctions.
AB  - Gap junctions (GJs) are specialized cell-cell contacts formed by connexins (Cxs),
      which provide direct intercellular communication between eukaryotic cells.
      Although Cx43 has long been known to be a substrate for ubiquitination, the
      reversal of this modification by deubiquitylases (DUBs) has never been described.
      Here we report that the DUB-associated molecule with the SH3 domain of STAM
      (AMSH) interacts with Cx43 and mediates its deubiquitination. In this study, we
      demonstrate that Cx43 is modified with lysine 63-linked polyubiquitin chains and
      that these increase the interaction between Cx43 and AMSH. We also show that AMSH
      is recruited to GJ plaque sites at the plasma membrane, where it mediates the
      deubiquitination of Cx43. Using siRNA depletion or overexpression of a
      catalytically inactive mutant of AMSH, we show that by decreasing Cx43
      deubiquitination, both the internalization and degradation rate of Cx43 are
      increased. Overall, these data strongly suggest that AMSH-mediated
      deubiquitination of Cx43 protects GJs from degradation.

PMID- 25070370
TI  - Formation of a nickel carbon dioxide adduct and its transformation mediated by a
      Lewis acid.
AB  - An uncommon nickel dinitrogen adduct and its tendency toward CO2 binding are
      investigated using a (PP(Me)P)Ni scaffold. (PP(Me)P)Ni(N2) (1) and
      {(PP(Me)P)Ni}2(MU-N2) (2) were prepared and their treatment with CO2 revealed the
      formation of (PP(Me)P)Ni(eta(2)-CO2) (3). This is a new type of CO2 binding for a
      zero-valent nickel center supported by three donor ligands, reminiscent of the
      CODH active site environment. Clear unique structural differences in 3 are
      evident when compared with previous 4-coordinate Ni-CO2 adducts. Compound 3 when
      treated with B(C6F5)3 gives the Lewis acid-base adduct (PP(Me)P)Ni{COOB(C6F5)3}
      (4) possessing a Ni-MU-CO2-kappa(2)C,O-B moiety.

PMID- 25070369
TI  - LKB1 and AMPK differentially regulate pancreatic beta-cell identity.
AB  - Fully differentiated pancreatic beta cells are essential for normal glucose
      homeostasis in mammals. Dedifferentiation of these cells has been suggested to
      occur in type 2 diabetes, impairing insulin production. Since chronic fuel excess
      ("glucotoxicity") is implicated in this process, we sought here to identify the
      potential roles in beta-cell identity of the tumor suppressor liver kinase B1
      (LKB1/STK11) and the downstream fuel-sensitive kinase, AMP-activated protein
      kinase (AMPK). Highly beta-cell-restricted deletion of each kinase in mice, using
      an Ins1-controlled Cre, was therefore followed by physiological, morphometric,
      and massive parallel sequencing analysis. Loss of LKB1 strikingly (2.0-12-fold,
      E<0.01) increased the expression of subsets of hepatic (Alb, Iyd, Elovl2) and
      neuronal (Nptx2, Dlgap2, Cartpt, Pdyn) genes, enhancing glutamate signaling.
      These changes were partially recapitulated by the loss of AMPK, which also up
      regulated beta-cell "disallowed" genes (Slc16a1, Ldha, Mgst1, Pdgfra) 1.8- to 3.4
      fold (E < 0.01). Correspondingly, targeted promoters were enriched for neuronal
      (Zfp206; P = 1.3 * 10(-33)) and hypoxia-regulated (HIF1; P = 2.5 * 10(-16))
      transcription factors. In summary, LKB1 and AMPK, through only partly overlapping
      mechanisms, maintain beta-cell identity by suppressing alternate pathways leading
      to neuronal, hepatic, and other characteristics. Selective targeting of these
      enzymes may provide a new approach to maintaining beta-cell function in some
      forms of diabetes.

PMID- 25070371
TI  - BRAT1 deficiency causes increased glucose metabolism and mitochondrial
      malfunction.
AB  - BACKGROUND: BRAT1 (BRCA1-associated ATM activator 1) interacts with both BRCA1,
      ATM and DNA-PKcs, and has been implicated in DNA damage responses. However, based
      on our previous results, it has been shown that BRAT1 may be involved in cell
      growth and apoptosis, besides DNA damage responses, implying that there are
      undiscovered functions for BRAT1. METHODS: Using RNA interference against human
      BRAT1, we generated stable BRAT1 knockdown cancer cell lines of U2OS, Hela, and
      MDA-MA-231. We tested cell growth properties and in vitro/in vivo tumorigenic
      potentials of BRAT1 knockdown cells compared to control cells. To test if loss of
      BRAT1 induces metabolic abnormalities, we examined the rate of glycolysis, ATP
      production, and PDH activity in both BRAT1 knockdown and control cells. The role
      of BRAT1 in growth signaling was determined by the activation of Akt/Erk, and
      SC79, Akt activator was used for validation. RESULTS: By taking advantage of
      BRAT1 knockdown cancer cell lines, we found that loss of BRAT1 expression
      significantly decreases cell proliferation and tumorigenecity both in vitro and
      in vivo. Cell migration was also remarkably lowered when BRAT1 was depleted.
      Interestingly, glucose uptake and production of mitochondrial ROS (reactive
      oxygen species) are highly increased in BRAT1 knockdown HeLa cells. Furthermore,
      both basal and induced activity of Akt and Erk kinases were suppressed in these
      cells, implicating abnormality in signaling cascades for cellular growth.
      Consequently, treatment of BRAT1 knockdown cells with Akt activator can improve
      their proliferation and reduces mitochondrial ROS concentration. CONCLUSIONS:
      These findings suggest novel roles of BRAT1 in cell proliferation and
      mitochondrial functions.

PMID- 25070372
TI  - Blood damage through a bileaflet mechanical heart valve: a quantitative
      computational study using a multiscale suspension flow solver.
AB  - Bileaflet mechanical heart valves (BMHVs) are among the most popular prostheses
      to replace defective native valves. However, complex flow phenomena caused by the
      prosthesis are thought to induce serious thromboembolic complications. This study
      aims at employing a novel multiscale numerical method that models realistic sized
      suspended platelets for assessing blood damage potential in flow through BMHVs. A
      previously validated lattice-Boltzmann method (LBM) is used to simulate pulsatile
      flow through a 23 mm St. Jude Medical (SJM) RegentTM valve in the aortic position
      at very high spatiotemporal resolution with the presence of thousands of
      suspended platelets. Platelet damage is modeled for both the systolic and
      diastolic phases of the cardiac cycle. No platelets exceed activation thresholds
      for any of the simulations. Platelet damage is determined to be particularly high
      for suspended elements trapped in recirculation zones, which suggests a shift of
      focus in blood damage studies away from instantaneous flow fields and toward high
      flow mixing regions. In the diastolic phase, leakage flow through the b-datum gap
      is shown to cause highest damage to platelets. This multiscale numerical method
      may be used as a generic solver for evaluating blood damage in other
      cardiovascular flows and devices. 

PMID- 25070374
TI  - Directed growth of electroactive metal-organic framework thin films using
      electrophoretic deposition.
AB  - Electrophoretic deposition (EPD) is used to assemble metal-organic framework
      (MOF) materials in nano- and micro-particulate, thin-film form. The flexibility
      of the method is demonstrated by the successful deposition of 4 types of MOFs: NU
      1000, UiO-66, HKUST-1, and Al-MIL-53. Additionally, EPD is used to pattern the
      growth of NU-1000 thin films that exhibit full electrochemical activity. 

PMID- 25070375
TI  - Clustered granules present in the hippocampus of aged mice result from a
      degenerative process affecting astrocytes and their surrounding neuropil.
AB  - Clusters of pathological granular structures appear and progressively increase in
      number with age in the hippocampus of several mice strains, markedly in the
      senescence-accelerated mouse prone 8 mice. In the present work, we performed an
      ultrastructural study of these granules paying special attention to the first
      stages of their formation, which have not been previously explored. The analysis
      of the immature granules allowed concluding that granules are not simple
      accumulations of molecular waste but the result of a degenerative process
      involving principally astrocytic processes, although nearby neuronal structures
      can be also affected. The granule generation includes the instability of the
      plasmatic membranes and the appearance of abnormal membranous structures that
      form intracellular bubbles or blebs of variable sizes and irregular shapes. These
      structures and some organelles degenerate producing some membranous fragments,
      and an assembly process of the resulting fragments generates the dense-core
      nucleus of the mature granule. Moreover, we found out that the neo-epitope
      recently described in the mature granules and localised abundantly in the
      membranous fragments of their dense-core nucleus emerges in the first stages of
      the granule formation. On the other hand, with this study, we increase the
      evidences that each cluster of granules is formed by the granules comprised in
      one astrocyte. A better knowledge of the causes of the granule formation and the
      function of the neo-epitope will help in both the interpretation of the
      physiological significance of the granules and their contribution to the
      degenerating processes in aging brain.

PMID- 25070376
TI  - Inhibition of the interleukin-23/interleukin-17 pathway by anti-interleukin-23p19
      monoclonal antibody attenuates 2,4,6-trinitrobenzene sulfonic acid-induced
      Crohn's disease in rats.
AB  - The interleukin (IL)-23/IL-17 pathway is considered to be important in the
      pathogenesis of Crohn's disease (CD). The present study aimed to evaluate the
      effects of targeting the IL-23/IL-17 pathway using the anti-IL-23p19 monoclonal
      antibody (mAb) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD rats. A
      total of 60 Sprague-Dawley rats were randomly divided into a control group, model
      group and an anti-IL-23p19 mAb treatment group (administered intramuscularly
      every week at a dose of 1 ml/mg). Disease activity index (DAI), colon macroscopic
      damage index (CMDI) and tissue damage index (TDI) were then evaluated. The mRNA
      expression of IL-23p19, p40 (IL-23/12), retinoic acid-related orphan receptor
      gammat (ROR-gammat) and IL-17 in colonic tissues were detected by reverse
      transcription-polymerase chain reaction and levels of serum IL-23p19, p40, ROR
      gammat and IL-17 were measured using an enzyme-linked immunosorbent assay. Anti
      IL-23p19 mAb was found to effectively attenuate colonic inflammation demonstrated
      by reduced DAI, CMDI and TDI scores, improvement in pathological evaluation and
      downregulation of expression levels of IL-23p19, p40 (IL-23/12), ROR-gammat and
      the downstream proinflammatory cytokine, IL-17. Anti-IL-23p19 mAb attenuated TNBS
      induced CD in model rats. The possible underlying mechanisms may be associated
      with inhibition of the IL-23/IL-17 pathway by inhibiting the expression of IL
      23p19 and downregulating the downstream proinflammatory cytokine IL-17. Targeting
      the IL-23/IL-17 pathway may be a relevant and realistic therapeutic approach for
      the development of additive and alternative treatments to the biologics currently
      available in the treatment of CD.

PMID- 25070373
TI  - Computed tomography arthrography with traction in the human hip for three
      dimensional reconstruction of cartilage and the acetabular labrum.
AB  - AIM: To develop and demonstrate the efficacy of a computed tomography
      arthrography (CTA) protocol for the hip that enables accurate three-dimensional
      reconstructions of cartilage and excellent visualization of the acetabular
      labrum. MATERIALS AND METHODS: Ninety-three subjects were imaged (104 scans); 68
      subjects with abnormal anatomy, 11 patients after periacetabular osteotomy
      surgery, and 25 subjects with normal anatomy. Fifteen to 25 ml of contrast agent
      diluted with lidocaine was injected using a lateral oblique approach. A Hare
      traction splint applied traction during CT. The association between traction
      force and intra-articular joint space was assessed qualitatively under
      fluoroscopy. Cartilage geometry was reconstructed from the CTA images for 30
      subjects; the maximum joint space under traction was measured. RESULTS: Using the
      Hare traction splint, the intra-articular space and boundaries of cartilage could
      be clearly delineated throughout the joint; the acetabular labrum was also
      visible. Dysplastic hips required less traction (~5 kg) than normal and
      retroverted hips required (>10 kg) to separate the cartilage. An increase in
      traction force produced a corresponding widening of the intra-articular joint
      space. Under traction, the maximum width of the intra-articular joint space
      during CT ranged from 0.98-6.7 mm (2.46 +/- 1.16 mm). CONCLUSIONS: When applied
      to subjects with normal and abnormal hip anatomy, the CTA protocol presented
      yields clear delineation of the cartilage and the acetabular labrum. Use of a
      Hare traction splint provides a simple, cost-effective method to widen the intra
      articular joint space during CT, and provides flexibility to vary the traction as
      required.

PMID- 25070377
TI  - Analysis of monoclonal antibody by a novel CE-UV/MALDI-MS interface.
AB  - mAbs are highly complex proteins that present a wide range of microheterogeneity
      that requires multiple analytical methods for full structure assessment and
      quality control. As a consequence, the characterization of mAbs on different
      levels is particularly product- and time-consuming. CE-MS couplings, especially
      to MALDI, appear really attractive methods for the characterization of biological
      samples. In this work, we report the last instrumental development and
      performance of the first totally automated off-line CE-UV/MALDI-MS/MS. This
      interface is based on the removal of the original UV cell of the CE apparatus,
      modification of the spotting device geometry, and creation of an integrated
      delivery matrix system. The performance of the method was evaluated with
      separation of five intact proteins and a tryptic digest mixture of nine proteins.
      Intact protein application shows the acquisition of electropherograms with high
      resolution and high repeatability. In the peptide mapping approach, a total
      number of 154 unique identified peptides were characterized using MS/MS spectra
      corresponding to average sequence coverage of 64.1%. Comparison with NanoLC/MALDI
      MS/MS showed complementarity at the peptide level with an increase of 42% when
      using CE/MALDI-MS coupling. Finally, this work represents the first analysis of
      intact mAb charge variants by CZE using an MS detection. Moreover, using a
      peptide mapping approach CE-UV/MALDI-MS/MS fragmentation allowed 100% sequence
      coverage of the light chain and 92% of the heavy chain, and the separation of
      four major glycosylated peptides and their structural characterization. 

PMID- 25070378
TI  - Long-term stability of beam quality and output of conventional X-ray units.
AB  - Conventional diagnostic X-ray units are used for radiographic imaging in many
      countries. For obtaining entrance surface doses, a numerical dose determination
      method has been applied in Japan. Although this technique is effective, it has to
      account for errors, particularly fluctuations, due to the beam quality and output
      of X-ray tubes. As a part of our quality control procedures, we recorded the
      entrance surface air kerma, tube voltage, and half-value layer measurements made
      for four diagnostic X-ray tubes over a 103-week period. The entrance surface air
      kerma for one of the four X-ray tubes had increased significantly by 11.4 % over
      1 year from its initial setting, whereas the tube voltages and half-value layers
      did not deviate significantly from their initial values. Medical physicists and
      radiological technologists should be aware of this fluctuation for diagnostic X
      ray tubes and take it into consideration when calculating the entrance surface
      air kerma. 

PMID- 25070379
TI  - MicroRNA-495 induces breast cancer cell migration by targeting JAM-A.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that function as post
      transcriptional regulators of gene expression. The deregulated expression of
      miRNAs is associated with a variety of diseases, including breast cancer. In the
      present study, we found that miR-495 was markedly up-regulated in clinical breast
      cancer samples by quantitative real time-PCR (qRT-PCR). Junctional adhesion
      molecule A (JAM-A) was predicted to be a potential target of miR-495 by
      bioinformatics analysis and was subsequently verified by luciferase assay and
      Western blotting. JAM-A was found to be negatively correlated with the migration
      of breast cancer cells through loss-of-function and gain-of-function assays, and
      the inhibition of JAM-A by miR-495 promoted the migration of MCF-7 and MDA-MB-231
      cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast
      cancer cell migration. Taken together, our findings suggest that miR-495 could
      facilitate breast cancer progression through the repression of JAM-A, making this
      miRNA a potential therapeutic target. 

PMID- 25070381
TI  - Left ventricular geometry and matrix metalloproteinases 2 and 9 in chronic Chagas
      heart disease.

PMID- 25070380
TI  - Comparison of the Framingham Risk Score, SCORE and WHO/ISH cardiovascular risk
      prediction models in an Asian population.
AB  - BACKGROUND: Cardiovascular risk-prediction models are used in clinical practice
      to identify and treat high-risk populations, and to communicate risk effectively.
      We assessed the validity and utility of four cardiovascular risk-prediction
      models in an Asian population of a middle-income country. METHODS: Data from a
      national population-based survey of 14,863 participants aged 40 to 65 years, with
      a follow-up duration of 73,277 person-years was used. The Framingham Risk Score
      (FRS), SCORE (Systematic COronary Risk Evaluation)-high and -low cardiovascular
      risk regions and the World Health Organization/International Society of
      Hypertension (WHO/ISH) models were assessed. The outcome of interest was 5-year
      cardiovascular mortality. Discrimination was assessed for all models and
      calibration for the SCORE models. RESULTS: Cardiovascular risk factors were
      highly prevalent; smoking 20%, obesity 32%, hypertension 55%, diabetes mellitus
      18% and hypercholesterolemia 34%. The FRS and SCORE models showed good agreement
      in risk stratification. The FRS, SCORE-high and -low models showed good
      discrimination for cardiovascular mortality, areas under the ROC curve (AUC) were
      0.768, 0.774 and 0.775 respectively. The WHO/ISH model showed poor
      discrimination, AUC=0.613. Calibration of the SCORE-high model was graphically
      and statistically acceptable for men (chi(2) goodness-of-fit, p=0.097). The SCORE
      low model was statistically acceptable for men (chi(2) goodness-of-fit, p=0.067).
      Both SCORE-models underestimated risk in women (p<0.001). CONCLUSIONS: The FRS
      and SCORE-high models, but not the WHO/ISH model can be used to identify high
      cardiovascular risk in the Malaysian population. The SCORE-high model predicts
      risk accurately in men but underestimated it in women.

PMID- 25070382
TI  - Clinical features associated with ictal osmophobia in migraine.
AB  - Olfactory hypersensitivity may occur during migraine attacks and has been found
      to be very specific for this form of headache. Aim of this study was to
      investigate if migraineurs with ictal osmophobia have particular clinical
      features comparing to patients without ictal osmophobia. We recruited 200
      consecutive migraineurs. Other primary headaches comorbidity and migraine
      prophylaxis were exclusion criteria. Each patient was interviewed following a
      structured questionnaire including general features about migraine, depression
      and anxiety symptoms. Migraine triggers both spontaneously and selecting from a
      specific list. Allodynia during the migraine attack was measured using the
      Allodynia symptoms check-list 12 (ASC-12). Eighty four (42 %) patients are non
      osmophobic vs. 116 patients (58 %) who are osmophobic. After a logistic
      regression analysis, pain intensity (OR 1.391; p = 0.008) and anxiety (OR 1.099;
      p = 0.047) were significantly higher while aura (OR 0.421; p = 0.028) is less
      frequent in osmophobic migraineurs. We found significant differences in clinical
      features of osmophobic patients in respect to non-osmophobic ones. Ictal
      osmophobia seems being related to a broader sensorial hypersensitivity that could
      lead to a more florid clinical presentation. 

PMID- 25070383
TI  - Prospective, case-control study on the effect of pregnancy on seizure frequency
      in women with epilepsy.
AB  - To evaluate if pregnancy induces a change in seizure frequency and in percentage
      of subjects remaining seizure-free. This is a prospective case-control study
      conducted in our tertiary epilepsy centre. Controls were matched 2:1 with the
      cases for relevant clinical parameters. Cases had to be referred to our centre
      for at least 9 months before-pregnancy, during pregnancy and the-9-months-after
      birth. Controls were followed for the correspondent periods of time: named
      respectively control period 1-2-3. Seizure frequency was defined as "improved" if
      there was a 50 % of reduction, "worsened" if there was a 50 % of increase, and
      "unchanged" in the rest of cases. We recruited 36 cases and 72 controls [in both
      group mean age was 28 years, partial epilepsy (80.6 %), generalized epilepsy
      (19.4 %)]; 30 cases and 60 controls were seizure-free before pregnancy and in
      period 1, respectively. During pregnancy 72 % of cases remained "unchanged" while
      8 and 19 % respectively "improved" and "worsened"; moreover, there was no
      statistical difference in the number of seizure-free patients and in the monthly
      seizure frequencies. No differences were found in controls. In this prospective
      case-control study, pregnancy does not affect seizure frequency in women with
      epilepsy. 

PMID- 25070384
TI  - Culprit of diffusion-weighted image in acute vestibular syndrome.

PMID- 25070385
TI  - Transthoracic echocardiography as an alternative major guidance to angiography
      during transcatheter closure of patent ductus arteriosus: technical feasibility
      and clinical relevance.
AB  - The conventional transcatheter closure of patent ductus arteriosus (PDA) requires
      femoral artery puncture and angiography for duct anatomic and shunting
      estimation. If such estimation can be replaced by transthoracic echocardiography
      (TTE), the procedure will be further simplified, with fewer invasions. This study
      aimed to examine whether TTE can serve as an alternative to aorta angiography and
      as a major guidance for transcatheter duct closure. The study enrolled 298
      consecutive patients (71 males and 227 females) with PDA. In the study, TTE with
      combined two-dimensional echocardiography (2DE) imaging and color-coded flow
      imaging (CDFI) was performed to measure the minimal shunting width (MSW) as the
      estimated minimal duct size for selection of an Amplatzer duct occluder (ADO) and
      to monitor the transcatheter duct closure intraprocedurally. The MSW was
      validated against the duct-stretched diameter (SDD), against the minimal waist
      diameter of the conical part of a released occluder measured by X-ray spot
      picture after successful duct closure (SDC), and against the size of the finally
      used ADO (SADO). Good correlation was found between MSW and SDD [SDD (mm) = 1.31
      MSW; r = 0.89; p < 0.01] and between MSW and SADO [SADO (mm) = 1.71 MSW; r =
      0.88; p < 0.01]. Of 296 patients who received occlusion using MSW as the
      reference for selection of the occluder, SDC was attained in 288 (97.3%), 5
      (1.7%), and 2 (0.7%) patients, respectively, at the first, second (1 ADO
      replacement), and third (2 ADO replacements) occluding attempt. Acute occluder
      dislodgement occurred in one patient (0.3%). At the 12-month follow-up
      assessment, no major complications were found, and the total immediate or 12
      month SDC was 99.7%. Echocardiography as an alternative major guidance to
      angiography for transcatheter duct closure is technically feasible, and TTE
      guidance can further simplify the procedure, with fewer invasions and potential
      complications.

PMID- 25070386
TI  - Cardiorespiratory fitness in children: a simple screening test for population
      studies.
AB  - Cardiorespiratory fitness is one measure of body functions, and its assessment
      should play an important role in the activities associated with the promotion of
      physical activity as an important component of a healthy lifestyle. This study
      aimed to develop a reference system of the mean post-exercise heart rate (HRmean
      post-ex) after a 3-min step test for use in screening the cardiorespiratory
      fitness of 6- to 12-year-old children. The study included 14,501 children ages 6
      12 years from primary schools in Gdansk. The participants were subjected to the 3
      min Kasch Pulse Recovery Test (KPR Test). The reference range for the
      classification of cardiorespiratory fitness was developed on the basis of the age
      specific percentile distribution of HRmean post-ex in 6- to 9- and 10- to 12-year
      old children. This study showed that the 3-min KPR Test is easy to perform and
      well tolerated by school-age children. As such, it can constitute a useful tool
      for health promoters and educators. The presented age- and gender-specific
      reference range of HRmean post-ex enables the assessment and monitoring of
      submaximal exercise-induced changes in the cardiovascular system and,
      consequently, the physical fitness of a given individual.

PMID- 25070387
TI  - Evaluation of post-contrast myocardial t1 in duchenne muscular dystrophy using
      cardiac magnetic resonance imaging.
AB  - The objective of the study was to perform a retrospective pilot study to evaluate
      the potential of myocardial T1 in assessment of Duchenne muscular dystrophy (DMD)
      cardiomyopathy. Early identification of DMD cardiac disease, particularly
      myocardial fibrosis, would allow earlier therapy, potentially improving outcomes.
      Shortened myocardial T1 measured by cardiac MRI (CMR) is a measure of cardiac
      fibrosis that may be detected before late gadolinium enhancement (LGE). We
      hypothesized that the post-contrast T1 obtained from the Look-Locker sequences
      (T1LL), an easily obtainable surrogate of myocardial T1, would be abnormally
      shortened in DMD compared with controls. T1LL measurement was performed on 21 DMD
      subjects and 11 controls; to account for individual variations in gadolinium
      distribution, myocardial T1LL was divided by blood pool T1LL, deriving T1LL
      ratios. DMD subjects had shorter mean T1LL ratio than controls (1.42 vs 1.72, p <
      0.001). Subset analyses in DMD subjects with normal LVEF and without LGE also
      demonstrated significantly shorter T1LL ratio (-0.28, p < 0.001 and -0.25, p =
      0.028). Post-contrast T1LL ratio is abnormally shortened in DMD compared with
      controls, even in DMD patients with otherwise normal CMRs. The application of
      more aggressive therapy for those with shorter T1LL may favorably alter morbidity
      and improve mortality associated with DMD cardiomyopathy. These data suggest that
      further prospective evaluation of myocardial T1 will be of benefit to patients
      with DMD. 

PMID- 25070388
TI  - Factors of negativity of electrophysiological study in children and teenagers
      complaining of tachycardia and prognostic significance.
AB  - When non-invasive studies remain negative, the diagnosis of unexplained
      tachycardia in the young is a dilemma. The purpose of the study was to determine
      the factors of negativity of transesophageal electrophysiological study (EPS) in
      children/teenagers complaining of tachycardia and the prognostic value. Two
      hundred and seventy-three children with a normal ECG in sinus rhythm, aged from 6
      to 19 years (15 +/- 3), complained of tachycardia. Transesophageal EPS consisted
      of atrial stimulation in control state and after isoproterenol. Supraventricular
      tachycardia (SVT) was induced in 149 patients (group I) and EPS remained negative
      in 124 (group II). Age did not differ (15 +/- 3 vs 15 +/- 3). Female gender and
      familial history of SVT were as frequent in group I (47, 11%) than in group II
      (55%, p = 0.15; 7%;p = 0.2). Feeling of dizziness/syncope with tachycardia was
      less frequent in group I (12%) than in group II (48%) (p < 0.0001). Feeling of
      chest pain with tachycardia was less frequent in group I (2%) than in group II
      (28%) (p < 0.0001). The presence of non-cardiac disease was less frequent in
      group I (1.3%) than in group II (6.4%) (p < 0.025). Patients with negative study
      remained free of SVT after a follow-up of 3.5 +/- 3 years, but one had a complete
      AV block. In children with apparently normal ECG in sinus rhythm, who complained
      of tachycardia clinical history (association with syncope, chest pain, or the
      presence of another disease) can predict negativity of EPS with a relatively high
      accuracy; EPS may not be necessary. In very symptomatic patients, transesophageal
      EPS, which is inexpensive and non-invasive, might be performed to stop
      investigations.

PMID- 25070389
TI  - The use of intracardiac echocardiography during percutaneous pulmonary valve
      replacement.
AB  - High-quality live imaging assessment of cardiac valves and cardiac anatomy is
      crucial for the success of catheter-based procedures. We present our experience
      using Intracardiac echocardiography (ICE) during transcatheter Percutaneous
      Pulmonary Valve replacement (tPVR).This is a retrospective study that included 35
      patients who underwent tPVR between April 2008 and June 2012. Thirty-one of these
      patients had the procedure performed under continuous ICE guidance. Pre-procedure
      transthoracic echocardiography (TTE) was obtained in all patients. ICE was
      performed at baseline, during the procedure, and at the conclusion of the
      procedure. Comparisons between the pre-procedure TTE and baseline ICE data and
      between post-procedure ICE data and the following day TTE were performed. Total
      of 35 patients had tPVR during the above-mentioned time period. Twenty-one
      patients received the Edwards Sapien valve and 14 patients had the Melody valve.
      Thirty-one patients had the procedure performed under continuous ICE guidance.
      The mean Pre-TTE peak gradient (PG) and Pre-ICE-PG were 45.5 +/- 20 vs 33 +/- 13
      mmHg (p < 0.001) and the mean Pre-TTE mean gradient (MG) and Pre-ICE-MG were 27.7
      +/- 13 vs 21 +/- 18 mmHg (p < 0.001). The mean Post-TTE- PG and Post-ICE-PG were
      24.3 +/- 11 vs 15.3 +/- 7 mmHg (p < 0.001) and the mean of the Post-TTE-MG and
      Post-ICE-MG were 14.2 +/- 7 vs 8.4 +/- 4 mmHg (p < 0.001). There was a good
      correlation between peak ICE and TTE gradient at baseline and after valve
      placement. For the degree of pulmonary regurgitation, there was no significant
      difference between TTE and ICE. ICE is an important modality to guide tPVR in
      patients with dysfunctional homograft valve between the right ventricle and
      pulmonary artery and should be used to assess valve function before, during and
      immediately after the procedure.

PMID- 25070390
TI  - Early and mid-term results of the arterial switch operation in patients with
      intramural coronary artery.
AB  - Intramural coronary artery is known to be a risk factor for early death after an
      arterial switch operation (ASO). We evaluated the early and mid-term results of
      ASO for patients with intramural coronary artery. From September 2008 to March
      2012, seven patients with an intramural coronary artery underwent ASO at our
      hospital. The mean age at operation was 2.4 months (2 days-1 year), and the mean
      body weight was 4.3 +/- 2.2 kg. The mean follow-up was 35.3 +/- 16.5 months (22
      63 months). The individual coronary button technique was used in seven patients.
      The intramural segment was unroofed in one patient; in one patient with
      myocardial ischemia, the intramural segment was unroofed and enlarged using a
      patch of autologous pericardium. There was one operative death because of low
      cardiac output syndrome (14.2% mortality). In the same time period at our
      hospital, three deaths were reported in 68 ASO patients (4.4% mortality) without
      an intramural coronary artery. There was no statistical difference between the
      two groups (P > 0.05). There were no late deaths, and no patients required a
      coronary intervention. Intramural coronary artery is a well-known risk factor for
      early death after ASO. To optimize results, the coronary transfer technique
      should be tailored to each patient's particular anatomy. Intraoperative or
      postoperative myocardial ischemia should be addressed aggressively by immediately
      reimplanting the coronary artery. Unroofing the intramural segment, even the
      distal portion, should restore normal coronary blood flow.

PMID- 25070391
TI  - Development of major aorto-pulmonary collateral arteries in vegf120/120 isoform
      mouse embryos with tetralogy of fallot.
AB  - The degree of right ventricular outflow tract obstruction, pulmonary stenosis
      (PS) and the development of major aorto-pulmonary collateral arteries (MAPCAs) in
      patients with tetralogy of Fallot (TOF) is related to clinical outcome.
      Vegf120/120 mutant mouse embryos develop TOF with various degrees of PS,
      comparable to humans. We aimed to study the ontogeny of the development of MAPCAs
      in this mouse model. The development of the right ventricular outflow tract,
      pulmonary arteries, and ductus arteriosus (DA) and formation of MAPCAs were
      studied in both wild type as well as Vegf120/120 mice from embryonic day 10.5
      until day 19.5. Of the 49 Vegf120/120 embryos, 35 embryos (71%) had ventral
      displacement of the outflow tract and a subaortic ventricular septal defect. A
      time-related development in severity of PS to pulmonary atresia (PA) was
      observed. From embryonic day 12.5, hypoplasia of the DA was seen in 13 (37%) and
      absent DA in 12 (37%) of these embryos. The 3 (6%) embryos with PA and absent DA
      developed MAPCAs, after day 15.5. In all, the MAPCAs arose from both subclavian
      arteries, running posterior in the thoracic cavity, along the vagal nerve. The
      MAPCAs connected the pulmonary arteries at the site of the hilus. A time-related
      development of PS to PA can lead, in combination with absent DA, to the
      development of MAPCAs later in embryonic life as an alternative route for
      pulmonary perfusion in this mouse model. This finding contributes to a better
      understanding of the consecutive morphological changes in the development toward
      MAPCAs in humans.

PMID- 25070392
TI  - Effects of biceps tension and superior humeral head translation on the glenoid
      labrum.
AB  - We sought to understand the effects of superior humeral head translation and load
      of the long head of biceps on the pathomechanics of the superior glenoid labrum
      by predicting labral strain. Using micro-CT cadaver images, a finite element
      model of the glenohumeral joint was generated, consisting of humerus, glenoid
      bone, cartilages, labrum, and biceps tendon. A glenohumeral compression of 50 N
      and biceps tensions of 0, 22, 55, and 88 N were applied. The humeral head was
      superiorly translated from 0 to 5 mm in 1-mm increments. The highest labral
      strain occurred at the interface with the glenoid cartilage and bone beneath the
      origin of the biceps tendon. The maximum strain was lower than the reported
      failure strain. The humeral head motion had relatively greater effect than biceps
      tension on the increasing labral strain. This supports the mechanistic hypothesis
      that superior labral lesions result mainly from superior migration of the humeral
      head, but also from biceps tension

PMID- 25070393
TI  - An acute clinical comparison of corneal staining and comfort associated with
      contact lens care solutions.
AB  - PURPOSE: This study compared the biocompatibility and comfort of 4 lens care
      solutions currently marketed in France. METHODS: This was a randomized,
      interventional, double-masked, single-center crossover study assessing balafilcon
      A silicone hydrogel contact lenses, bilaterally, straight from the blister pack
      solution (control) and pre-soaked in the following lens care solutions:
      Regard((r)) (containing sodium chlorite), ReNu((r)) (containing a PHMB
      [polyhexamethylene biguanide] derivative), CyCleanTM and MeniCareTM Soft (both
      containing PHMB). Subjects were randomized to the order of test solution use. For
      each of the 5 solutions tested, subjects attended a baseline/lens dispensing
      visit and an intervention visit 2h later. At both visits, evaluation included
      slit-lamp examination, corrected-distance visual acuity, corneal staining, and
      subject-assessed photophobia, ocular comfort, and ocular redness. RESULTS: Thirty
      subjects were enrolled and 28 were evaluable. Corneal staining severity was
      significantly worse than baseline after 2h of wearing lenses soaked in CyClean,
      MeniCare, or ReNu (P<=0.001). The MeniCare group alone demonstrated a significant
      improvement in ocular comfort after 2h of lens wear (P=0.02). No group
      demonstrated significant changes in ocular redness or photophobia. Corrected
      distance visual acuity was similar between baseline and intervention visits for
      each test solution. No adverse events were reported during the study.
      CONCLUSIONS: Silicone hydrogel contact lenses presoaked in lens solutions
      containing PHMB or a PHMB derivative produced an increase in corneal staining
      after 2h of lens wear. The higher levels of corneal staining in the 2 solutions
      did not correlate with increased discomfort within this 2-h timeframe.

PMID- 25070394
TI  - Differential DNA methylation status between breast carcinomatous and normal
      tissues.
AB  - Breast cancer has been considered to be a multifactorial disease with a wide
      array of well-characterized gene mutations and chromosomal abnormalities.
      However, it is becoming evident that the onset or development of breast cancer
      also depends on epigenetic factors, although the mechanisms have not been fully
      elucidated. We performed a genome-wide analysis of DNA methylation of breast
      carcinomatous tissues and paired normal tissues to examine the differences in
      methylation between them. Methylation-specific polymerase chain reaction (MSP)
      was used to validate the hypermethylated genes screened out by DNA methylation
      microarray. We found that hypomethylation and hypermethylation occurred in 2753
      and 1795 genes, respectively, in breast carcinomatous tissues. Meanwhile, gene
      ontology analysis and ingenuity pathway analysis revealed the function and
      pathway of several genes whose methylation status was altered in breast
      carcinomatous tissues. In addition, we investigated the promoter methylation
      status of four genes in breast carcinomatous tissue and paired normal tissues
      (n=30) by MSP. Promoter hypermethylation of CRABP1, HOXB13, IFNGR2, and PIK3C3
      was found in 37% (11/30), 23% (7/30), 17% (5/30), and 2% (2/30) of the
      carcinomas, respectively. Mutation of these four important genes was critical to
      many types of cancer. Our results suggest that DNA methylation mechanisms may be
      involved in regulating the occurrence and development of breast cancer. 

PMID- 25070395
TI  - Inhibition of annexin A7 gene and protein induces the apotosis and decreases the
      invasion, migration of the hepatocarcinoma cell line.
AB  - Our previous studies have shown that annexin A7 (ANXA7) gives different
      expressions in the mouse hepatocarcinoma cell lines with low or high lymphatic
      metastatic potential in both gene and protein levels. In this study, whether by
      using RNA interference (RNAi) technique downregulating ANXA7 in the gene level or
      by using antibody against ANXA7 in the protein level, the depressed expression of
      ANXA7 could induce apotosis and decrease the invasion, migration capacities of
      the Hca-P cell, a hepatocarcinoma cell line with low lymphatic metastatic
      potential in vitro. The results indicate that ANXA7 is an important factor in
      tumors with the lymphatic metastasis. 

PMID- 25070396
TI  - Association of statins and risk of fractures in a military health system: a
      propensity score-matched analysis.
AB  - BACKGROUND: Contradictory evidence exists regarding statin use and risk of
      osteoporotic fractures. OBJECTIVE: The study objective was to examine the effect
      of statins on fracture risk in a Military Healthcare System (MHS) with similar
      access and standard of health care for its beneficiaries. METHODS: This is a
      retrospective study of patients enrolled in an MHS encompassing the period from
      October 1, 2003, to March 1, 2010. Statin users were defined as those receiving a
      statin for >=90 days in Fiscal Year 2005, whereas nonusers were defined as
      individuals not receiving a statin throughout the study period. A propensity
      score-matched cohort of statin users and nonusers was created using 42 variables.
      The outcomes were identified using ICD-9-CM codes in the follow-up period
      (October 1, 2006, to March 1, 2010). In all, 4 outcomes were examined: all
      fractures, femoral neck fractures, upper-extremity fractures, and lower-extremity
      fractures. RESULTS: Of 46 249 patients, 6967 pairs of statin users and nonusers
      were matched. Statin users had a lower risk of femoral neck fracture in
      comparison to nonusers (odds ratio=0.58, 95% CI=0.36-0.94) but similar risk of
      all fractures, lower-extremity fractures, and upper-extremity fractures.
      CONCLUSIONS: In this cohort of patients managed in an MHS, statin use was
      associated with a lower risk of femoral neck fractures, but not all fractures,
      upper-extremity fractures, or lower-extremity fractures.

PMID- 25070397
TI  - Ascorbate- and zinc-responsive parkinsonism.
AB  - OBJECTIVE: To report a case of Parkinsonism rapidly responsive to intravenous
      replacement of vitamin C and zinc. CASE SUMMARY: A 66-year-old man with
      Parkinsonism, pleural effusion, and bipolar disorder was found to have low serum
      vitamin C and zinc levels. Intravenous replacement of these micronutrients led to
      resolution of the movement disorder in less than 24 hours. DISCUSSION:
      Parkinsonism has been associated with vitamin C deficiency, and recent cases of
      scurvy complicated by Parkinsonism have responded well to intravenous replacement
      of vitamin C. In this case, deficiency of zinc may have contributed to the
      development of a movement disorder. The likely pathophysiology of, and treatment
      recommendations for, Parkinsonism linked to deficiencies of vitamin C and zinc
      are reviewed. CONCLUSIONS: Whereas vitamin C has a strong link with Parkinsonism,
      the potential role of zinc has only been suspected. This case report highlights
      some of the potential links between zinc deficiency and Parkinsonism.

PMID- 25070398
TI  - Effect of 5% lidocaine medicated plaster on pain intensity and paroxysms in
      classical trigeminal neuralgia.
AB  - OBJECTIVE: Trigeminal neuralgia (TN) is a neuropathic pain condition affecting
      one or more branches of the trigeminal nerve. It is characterized by unilateral,
      sudden, shock-like, and brief painful attacks, which follow the distribution of
      trigeminal nerve branches, and with no other accompanying sensorimotor or
      autonomic signs and symptoms. Current guidelines stipulate which therapies
      represent first-, second-, and third-line treatments for TN, but there is a
      consistent mismatch between the therapeutic guidelines and the patient's
      preferences and expectations. CASE SUMMARY: We report on 2 patients with
      classical TN in whom conventional drugs for TN were not tolerated. In these
      patients, treatment with 5% lidocaine medicated plaster (LMP) resulted in
      reduction of pain intensity and the number of pain paroxysms. DISCUSSION: LMP is
      known to block the sodium channels on peripheral nerves and may cause a selective
      and partial block of Adelta and C fibers. According to the TN ignition
      hypothesis, blockage of peripheral afferents by LMP may reduce pain paroxysms.
      The effect of LMP may outlast the pharmacokinetics of the drug by reducing pain
      amplification mechanisms in the central nervous system. LMP has limited or no
      systemic side effects. CONCLUSIONS: LMP may be an effective and well-tolerated
      treatment option for TN in those patients who do not tolerate or who refuse other
      therapies. Future randomized controlled studies should better address this issue.

PMID- 25070399
TI  - A staged approach for a lung-liver transplant patient using ex vivo reconditioned
      lungs first followed by an urgent liver transplantation.
AB  - Combined lung-liver transplantation is a logistically challenging procedure
      hampered by shortage of organ donors. We describe the case of a young patient
      with end-stage lung disease due to of cystic fibrosis and liver cirrhosis who
      needed combined lung-liver transplantation. The long waiting for this caused an
      interesting clinical dilemma. We decided to change our policy in this situation
      by listing him only for the lung transplantation and to apply for a high urgent
      liver transplantation if the liver failed after the lung transplantation. This
      strategy enabled us to use lungs treated with ex vivo lung perfusion (EVLP) from
      an unsuitable donor after circulatory death. After conditioning for 4 h via EVLP,
      the pO2 was 59.7 kPa. The lungs were transplanted successfully. He developed an
      acute-on-chronic liver failure for which he received a successful liver
      transplantation 19 days after the lung transplantation. 

PMID- 25070400
TI  - [Clinical results of a multifocal pseudophakic additional lens].
AB  - BACKGROUND: In order to meet the patients wish for compensation of presbyopia in
      a flexible way, even in cases of an already pseudophacic eye, sulcus-fixated
      additional intraocular lenses (IOL) have been developed as an alternative to
      multifocal IOLs (MIOL) in the capsular bag. This allows subsequent application of
      multifocal optics. Furthermore, these additional lenses offer a relatively simple
      opportunity for postoperative refractive fine tuning or, in cases of
      incompatibility, a minimally invasive explantation of the multifocal part of the
      optical system. PURPOSE: The objective of our work was the examination of a
      diffractive multifocal additional IOL and its functional characteristics.
      MATERIAL AND METHODS: In a prospective, monocentric trial 32 eyes of 21 patients
      had cataract surgery with implantation of a monofocal IOL into the capsular bag
      and simultaneous implantation of a multifocal additional IOL into the sulcus. The
      visual acuity was tested at different distances 6 weeks and 3 months
      postoperatively. At the 3 month follow-up contrast sensitivity and defocus curves
      were additionally assessed. Patients with bilateral implantation filled in a
      questionnaire to assess their subjective satisfaction of postoperative visual
      quality. RESULTS: All eyes had an uneventful postoperative course. At both follow
      ups an uncorrected distance and near visual acuity (VA) of 0.2 LogMAR or better
      was achieved. In intermediate vision 29 out of 32 eyes after 6 weeks and 31 out
      of 32 eyes after 3 months reached an uncorrected VA of 0.2 LogMAR or better. The
      defocus curves showed a typical two-peaked shape. At intermediate distance (-1.5
      D of defocus) the median VA was 0.35 LogMAR. Contrast sensitivity testing showed
      results in the upper region of the standard range of age-matched, healthy
      patients. DISCUSSION: The examined type of diffractive additional IOL achieved
      good to very good functional results, which are comparable to corresponding IOLs
      in the capsular bag. Multifocal additional IOLs can be considered as a useful
      extension of refractive surgical alternatives for the compensation of presbyopia.
      The possibility to implant the multifocal optic part independently of the primary
      surgery, the minimal invasivity of the procedure and the likewise time
      independent reversibility can be pointed out as special qualities of these IOL.

PMID- 25070401
TI  - Chlorpyrifos-induced changes in the antioxidants and fatty acid compositions of
      Chroococcus turgidus NTMS12.
AB  - This study investigated the effect of pesticide chlorpyrifos (CP) on a freshwater
      cyanobacterium Chroococcus turgidus NTMS12. The changes in chlorophyll-a,
      proline, superoxide dismutase (SOD), catalase (CAT) activities and fatty acid
      composition of the test organism were analysed. Organism was grown at 6, 9 and 12
      mg l(-1) of CP, and based on the chlorophyll-a content, 6 mg l(-1) of CP was
      found to be the tolerable concentration. Hence, 6 mg l(-1) of CP was taken to
      evaluate the concentration of proline and activities of SOD and CAT at 48-h
      exposure. The changes in the fatty acid profile were analysed after 7 days of
      exposure. Upon pesticide exposure, increased concentration of proline and
      activities of SOD and CAT were found. Significant changes in fatty acid profile
      have also been observed. However, polyunsaturated fatty acid content was
      decreased in treated cultures when compared with the untreated control. Changes
      in biochemical activities indicate that cyanobacteria C. turgidus NTMS12 undergo
      adaptive changes against CP-induced oxidative stress. SIGNIFICANCE AND IMPACT OF
      THE STUDY: : Chlorpyrifos induces oxidative stress in Chroococcus turgidus
      NTMS12. A strong inference was made on increased activity of antioxidant enzymes
      such as superoxide dismutase (SOD), catalase (CAT) and proline content and
      lowering the level of unsaturated fatty acids under the pesticide-exposed
      condition. These significant changes are the defence mechanisms against the
      oxidative stress. Thus, this organism holds great promise in resisting toxic
      pesticide.

PMID- 25070402
TI  - Skin irritation to glass wool or continuous glass filaments as observed by a
      patch test among human Japanese volunteers.
AB  - Glass wool and continuous glass filaments have been used in industry. We examined
      the irritability of those among Japanese. A patch test was performed on 43
      volunteers for the followings: glass wool for non-residential use with and
      without a urea-modified phenolic resin binder, that for residential use with and
      without the binder, and continuous glass filaments with diameters of 4, 7, 9, and
      13 um. Materials were applied to an upper arm of each volunteer for 24 h. The
      skin was observed at 1 and 24 h after the removal. At 1 h after removal, slight
      erythema was observed on the skin of a woman after the exposure to glass wool for
      residential use without the binder. Erythema was observed on the skin of another
      woman at 1 h after a 24-h exposure to glass wool for non-residential use without
      the binder. There were no reactions at 24 h after the removal. The low reactions
      in the patch test suggested that the irritability caused by glass wool,
      irrespective of a resin component, could be induced mechanically, and that the
      irritability caused by continuous glass filaments with resin could be slight and
      either mechanical or chemical. 

PMID- 25070403
TI  - Paper-based colorimetric array test strip for selective and semiquantitative
      multi-ion analysis: simultaneous detection of Hg2+, Ag+, and Cu2+.
AB  - A novel approach is presented in this article to qualitatively and
      semiquantitatively analyze multiple heavy metal ions simultaneously by a
      colorimetric array test strip. As a proof-of-concept application, a multi-ion
      analysis array test strip (for Hg(2+), Ag(+), and Cu(2+)) was fabricated through
      immobilizing five specifically responsive indicators in typical matrixes with
      tunable sensitivities. The as-obtained test strip shows not only high selectivity
      for Hg(2+), Ag(+), and Cu(2+), respectively, but also can be applied for their
      mixtures. The detection limit of the test strip is well below the Chinese
      wastewater discharge standard concentrations. Moreover, the array test strip
      demonstrates excellent anti-interference capability, detection, and production
      reproducibility, long-term storage stability, and real water sample
      applicability. 

PMID- 25070407
TI  - Oxidative catalysis using the stoichiometric oxidant as a reagent: an efficient
      strategy for single-electron-transfer-induced tandem anion-radical reactions.
AB  - Oxidative single-electron transfer-catalyzed tandem reactions consisting of a
      conjugate addition and a radical cyclization are reported, which incorporate the
      mandatory terminal oxidant as a functionality into the product. 

PMID- 25070404
TI  - Application of theory to enhance audit and feedback interventions to increase the
      uptake of evidence-based transfusion practice: an intervention development
      protocol.
AB  - BACKGROUND: Audits of blood transfusion demonstrate around 20% transfusions are
      outside national recommendations and guidelines. Audit and feedback is a widely
      used quality improvement intervention but effects on clinical practice are
      variable, suggesting potential for enhancement. Behavioural theory, theoretical
      frameworks of behaviour change and behaviour change techniques provide systematic
      processes to enhance intervention. This study is part of a larger programme of
      work to promote the uptake of evidence-based transfusion practice. OBJECTIVES:
      The objectives of this study are to design two theoretically enhanced audit and
      feedback interventions; one focused on content and one on delivery, and
      investigate the feasibility and acceptability. METHODS: Study A (Content): A
      coding framework based on current evidence regarding audit and feedback, and
      behaviour change theory and frameworks will be developed and applied as part of a
      structured content analysis to specify the key components of existing feedback
      documents. Prototype feedback documents with enhanced content and also a
      protocol, describing principles for enhancing feedback content, will be
      developed. Study B (Delivery): Individual semi-structured interviews with
      healthcare professionals and observations of team meetings in four hospitals will
      be used to specify, and identify views about, current audit and feedback
      practice. Interviews will be based on a topic guide developed using the
      Theoretical Domains Framework and the Consolidated Framework for Implementation
      Research. Analysis of transcripts based on these frameworks will form the
      evidence base for developing a protocol describing an enhanced intervention that
      focuses on feedback delivery. Study C (Feasibility and Acceptability): Enhanced
      interventions will be piloted in four hospitals. Semi-structured interviews,
      questionnaires and observations will be used to assess feasibility and
      acceptability. DISCUSSION: This intervention development work reflects the UK
      Medical Research Council's guidance on development of complex interventions,
      which emphasises the importance of a robust theoretical basis for intervention
      design and recommends systematic assessment of feasibility and acceptability
      prior to taking interventions to evaluation in a full-scale randomised study. The
      work-up includes specification of current practice so that, in the trials to be
      conducted later in this programme, there will be a clear distinction between the
      control (usual practice) conditions and the interventions to be evaluated.

PMID- 25070408
TI  - [Genetics and epigenetics. Explanatory approaches for (gender-specific)
      mechanisms of disease development].
AB  - Whereas the central role of DNA as the carrier of genetic information has long
      been well known, the impact of epigenetic mechanisms as mediators between genes
      and environment is now becoming increasingly clear. Epigenetics helps explain the
      partially reversible interplay between gene function and environment and even
      permits observation of the transgenerational transmission of epigenetic
      modifications. Of special interest are gender-specific mechanisms of gene
      regulation which, among others, offer an explanation for gender differences in
      human diseases. Since the study of epigenetic mechanisms and their impact on the
      etiology of common diseases is in its infancy, it is too early to draw general
      conclusions from the current state of knowledge. Moreover, completely new
      strategies are needed to research these effects. In addition to molecular
      findings, definitions of specific phenotypes are required, including biographic
      data of affected individuals and their ancestors. Epigenetics needs to be viewed
      in the context of the theory of evolution, classical genetics, and environmental
      research. Its aim is not to substitute the knowledge in these disciplines, but
      rather to provide a key to link their findings, thereby opening up new
      possibilities in terms of interpretation and understanding of gender differences
      in medicine. If these epigenetic mechanisms are better understood, particularly
      in terms of specific diseases, it is conceivable that these disorders could be
      influenced and treated in a more targeted manner in the future. 

PMID- 25070409
TI  - [Gender differences in depression].
AB  - Depression is one of the most prevalent and debilitating diseases. In recent
      years there has been increased awareness of sex- and gender-specific issues in
      depression. This narrative review presents and discusses differences in
      prevalence, symptom profile, age at onset and course, comorbidity, biological and
      psychosocial factors, the impact of sexual stereotyping, help-seeking, emotion
      regulation and doctor-patient communication. Typically, women are diagnosed with
      depression twice as often as men, and their disease follows a more chronic
      course. Comorbid anxiety is more prevalent in women, whereas comorbid alcohol
      abuse is a major concern in men. Sucide rates for men are between three and five
      times higher compared with women. Although there are different symptom profiles
      in men and women, it is difficult to define a gender-specific symptom profile.
      Socially mediated gender roles have a significant impact on psychosocial factors
      associated with risk, sickness behavior and coping strategies. In general, too
      little attention has been paid to the definition and handling of depression and
      the gender-related requirements it makes on the healthcare system. 

PMID- 25070410
TI  - [Living conditions: stumbling block or path to successful ageing? Results of the
      Augsburg regional conference "Living environment, age and health"].
AB  - In addition to good medical care, living environment is of central importance in
      encouraging social participation among older people. Therefore, municipalities
      should prioritise the age-appropriate design of living environments. Results of
      the KORA Age study were presented at the regional conference "Living environment,
      age and health" in the Augsburg town hall on October 1, 2013. The results on
      participation and living environment were discussed with local policy makers and
      senior citizens' representatives from Augsburg and two surrounding regions. The
      study examined the impact of living environment on participation using two
      different approaches: qualitative findings from focus group discussions and
      quantitative findings based on telephone interviews and the use of a geographic
      information system. The results were complemented by contributions from a
      regional and national perspective. It was stressed in the closing discussion that
      a senior-friendly living environment can only be created by using a broad range
      of different measures. On the one hand physical barriers need to be removed,
      while at the same time the sense of community, neighborhood cohesion and
      solidarity should be encouraged further. 

PMID- 25070411
TI  - Microbiological accumulation by the Mediterranean invasive alien species
      Branchiomma bairdi (Annelida, Sabellidae): potential tool for bioremediation.
AB  - We examined the bacterial accumulation and digestion in the alien polychaete
      Branchiomma bairdi. Microbiological analyses were performed on worm homogenates
      from "unstarved" and "starved" individuals and on seawater from the same sampling
      site (Ionian Sea, Italy). Densities of culturable heterotrophic bacteria (22 
      degrees C), total culturable bacteria (37  degrees C) and vibrios were measured
      on Marine Agar 2216, Plate Count Agar and TCBS Agar, respectively. Microbial
      pollution indicators were determined by the most probable number method. B.
      bairdi was able to accumulate all the six considered microbiological groups
      which, however, differ in their resistance to digestion. B. bairdi results more
      efficient than the other two co-occurring sabellids in removing bacteria
      suggesting that it may counteract the effects of microbial pollution playing a
      potential role for in situ bioremediation. Thus a potential risk, such as the
      invasion of an alien species, could be transformed into a benefit with high
      potential commercial gain and economic feasibility.

PMID- 25070412
TI  - Case of elderly patient who developed hallucinations upon administration of
      oseltamivir.

PMID- 25070413
TI  - A 21st century roadmap for human health risk assessment.
AB  - The Health and Environmental Sciences Institute (HESI)-coordinated Risk
      Assessment in the 21st Century (RISK21) project was initiated to develop a
      scientific, transparent, and efficient approach to the evolving world of human
      health risk assessment, and involved over 120 participants from 12 countries, 15
      government institutions, 20 universities, 2 non-governmental organizations, and
      12 corporations. This paper provides a brief overview of the tiered RISK21
      framework called the roadmap and risk visualization matrix, and articulates the
      core principles derived by RISK21 participants that guided its development.
      Subsequent papers describe the roadmap and matrix in greater detail. RISK21
      principles include focusing on problem formulation, utilizing existing
      information, starting with exposure assessment (rather than toxicity), and using
      a tiered process for data development. Bringing estimates of exposure and
      toxicity together on a two-dimensional matrix provides a clear rendition of human
      safety and risk. The value of the roadmap is its capacity to chronicle the
      stepwise acquisition of scientific information and display it in a clear and
      concise fashion. Furthermore, the tiered approach and transparent display of
      information will contribute to greater efficiencies by calling for data only as
      needed (enough precision to make a decision), thus conserving animals and other
      resources.

PMID- 25070414
TI  - Risk assessment in the 21st century: roadmap and matrix.
AB  - Abstract The RISK21 integrated evaluation strategy is a problem formulation-based
      exposure-driven risk assessment roadmap that takes advantage of existing
      information to graphically represent the intersection of exposure and toxicity
      data on a highly visual matrix. This paper describes in detail the process for
      using the roadmap and matrix. The purpose of this methodology is to optimize the
      use of prior information and testing resources (animals, time, facilities, and
      personnel) to efficiently and transparently reach a risk and/or safety
      determination. Based on the particular problem, exposure and toxicity data should
      have sufficient precision to make such a decision. Estimates of exposure and
      toxicity, bounded by variability and/or uncertainty, are plotted on the X- and Y
      axes of the RISK21 matrix, respectively. The resulting intersection is a highly
      visual representation of estimated risk. Decisions can then be made to increase
      precision in the exposure or toxicity estimates or declare that the available
      information is sufficient. RISK21 represents a step forward in the goal to
      introduce new methodologies into 21st century risk assessment. Indeed, because of
      its transparent and visual process, RISK21 has the potential to widen the scope
      of risk communication beyond those with technical expertise. 

PMID- 25070416
TI  - Fiber-assisted molding (FAM) of surfaces with tunable curvature to guide cell
      alignment and complex tissue architecture.
AB  - A simple and robust method termed "fiber-assisted molding (FAM)" is presented to
      create biomimetic three-dimensional surfaces with controllable curvature and
      helical twist. The alignment of muscle fibrils and the assembly of helically
      patterned extracellular matrix by cells demonstrate the potential of this method
      for tissue engineering and other materials science applications. 

PMID- 25070417
TI  - Cambridge community Optometry Glaucoma Scheme.
AB  - BACKGROUND: With a higher life expectancy, there is an increased demand for
      hospital glaucoma services in the United Kingdom. DESIGN: The Cambridge community
      Optometry Glaucoma Scheme (COGS) was initiated in 2010, where new referrals for
      suspected glaucoma are evaluated by community optometrists with a special
      interest in glaucoma, with virtual electronic review and validation by a
      consultant ophthalmologist with special interest in glaucoma. PARTICIPANTS: 1733
      patients were evaluated by this scheme between 2010 and 2013. METHODS: Clinical
      assessment is performed by the optometrist at a remote site. Goldmann applanation
      tonometry, pachymetry, monoscopic colour optic disc photographs and automated
      Humphrey visual field testing are performed. A clinical decision is made as to
      whether a patient has glaucoma or is a suspect, and referred on or discharged as
      a false positive referral. The clinical findings, optic disc photographs and
      visual field test results are transmitted electronically for virtual review by a
      consultant ophthalmologist. MAIN OUTCOME MEASURES: The number of false positive
      referrals from initial referral into the scheme. RESULTS: Of the patients, 46.6%
      were discharged at assessment and a further 5.7% were discharged following
      virtual review. Of the patients initially discharged, 2.8% were recalled
      following virtual review. Following assessment at the hospital, a further 10.5%
      were discharged after a single visit. CONCLUSIONS: The COGS community-based
      glaucoma screening programme is a safe and effective way of evaluating glaucoma
      referrals in the community and reducing false-positive referrals for glaucoma
      into the hospital system.

PMID- 25070418
TI  - Effects of benthic macrofauna bioturbation on the bacterial community composition
      in lake sediments.
AB  - Benthic macrofauna are considered to be an important part of the lacustrine
      ecosystem, and bioturbation may greatly affect the biogeochemical processes and
      microbial activities in sediments. In the present study, the bacterial community
      composition in sediments inhabited by 3 different types of benthic macrofauna
      (Corbicula fluminea, Chironomidae larvae, and tubificid worms) in the shallow and
      eutrophic Lake Taihu was studied to investigate the different effects of
      bioturbation on the composition of these communities. Microcosms were
      constructed, and culture-independent methods, including terminal restriction
      fragment length polymorphism (T-RFLP) and clone library analysis, were performed
      to evaluate the bacterial communities. Analysis of similarities (ANOSIM) and
      multidimensional scaling (MDS) analysis of T-RFLP patterns demonstrated that
      differences in the bacterial community composition between the control and the
      macrofauna-inhabited sediments were not as great as expected, although the
      chemical properties of the sediments changed remarkably. Nevertheless, the
      dominant bacterial group in each type of macrofauna-inhabited sediment was
      different. Acidobacteria, Betaproteobacteria, and Deltaproteobacteria were the
      dominant bacterial groups in sediments inhabited by C. fluminea, tubificid worms,
      and Chironomidae larvae, respectively. The data obtained in this study are
      helpful for understanding the effects of bioturbation in a shallow, eutrophic
      lake. 

PMID- 25070419
TI  - Bowen's carcinoma of the penis with sebaceous differentiation associated with
      human papillomavirus type 16.

PMID- 25070420
TI  - The impact of cone beam computed tomography on the choice of endodontic
      diagnosis.
AB  - AIM: To determine whether the outcome of cone beam computed tomography (CBCT)
      examinations performed in accordance with the European Commission guidelines in a
      clinical setting has an impact on choosing diagnoses in endodontics. METHODOLOGY:
      A prospective observational study was conducted. Fifty-three consecutive patients
      (81 teeth) from two different endodontic specialist clinics in Sweden were
      followed. After performing a thorough clinical examination (based on the history,
      clinical findings, and diagnostic tests such as intra-oral radiography), the
      examiner wrote down a preliminary diagnosis before CBCT examination. After the
      CBCT examination, a new diagnosis was made by the same examiner. Both the pre-
      and the post-CBCT examination diagnoses were plotted according to patients and
      teeth. The CBCT examinations were performed using similar equipment and protocols
      that were standardized amongst the clinics. RESULTS: The diagnoses were changed
      for at least one tooth in 22 patients (41%); overall, the diagnoses were changed
      for 28 teeth (35%). CONCLUSION: CBCT has a substantial impact on diagnostic
      thinking in endodontics when used in accordance with the European Commission
      guidelines.

PMID- 25070415
TI  - The use of mode of action information in risk assessment: quantitative key
      events/dose-response framework for modeling the dose-response for key events.
AB  - The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to
      develop strategies for using all available data (in vitro, in vivo, and in
      silico) to advance the next-generation of chemical risk assessments. A goal of
      the Subteam is to enhance the existing Mode of Action/Human Relevance Framework
      and Key Events/Dose Response Framework (KEDRF) to make the best use of
      quantitative dose-response and timing information for Key Events (KEs). The
      resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a
      structured quantitative approach for systematic examination of the dose-response
      and timing of KEs resulting from a dose of a bioactive agent that causes a
      potential adverse outcome. Two concepts are described as aids to increasing the
      understanding of mode of action-Associative Events and Modulating Factors. These
      concepts are illustrated in two case studies; 1) cholinesterase inhibition by the
      pesticide chlorpyrifos, which illustrates the necessity of considering
      quantitative dose-response information when assessing the effect of a Modulating
      Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced
      uterotrophic responses in rodents, which demonstrate how quantitative dose
      response modeling for KE, the understanding of temporal relationships between KEs
      and a counterfactual examination of hypothesized KEs can determine whether they
      are Associative Events or true KEs.

PMID- 25070421
TI  - Evaluation of class I HDAC isoform selectivity of largazole analogues.
AB  - Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The
      majority of largazole analogues to date have modified the thiazole-thiazoline and
      the warhead moiety. In order to elucidate class I-specific structure-activity
      relationships, a series of analogues with modifications in the valine or the
      linker region were prepared and evaluated for their class I isoform selectivity.
      The inhibition profile showed that the C2 position of largazole has an optimal
      steric requirement for efficient HDAC inhibition and that substitution of the
      trans-alkene in the linker with an aromatic group results in complete loss of
      activity. This data will aid the design of class I isoform selective HDAC
      inhibitors. 

PMID- 25070424
TI  - Influence of substituent on equilibrium of benzoxazine synthesis from Mannich
      base and formaldehyde.
AB  - N-Substituted aminomethylphenol (Mannich base) and 3,4-dihydro-2H-3-substituted
      1,3-benzoxazine (benzoxazine) were synthesized from substituted phenol (p-cresol,
      phenol, p-chlorophenol), substituted aniline (p-toluidine, aniline, p
      chloroaniline) and formaldehyde to study influence of substituent on equilibrium
      of benzoxazine synthesis from Mannich base and formaldehyde. (1)H-NMR and charges
      of nitrogen and oxygen atoms illustrate effect of substituent on reactivity of
      Mannich base, while oxazine ring stability is characterized by differential
      scanning calorimetry (DSC) and C-O bond order. Equilibrium constants were tested
      from 50  degrees C to 80  degrees C, and the results show that substituent
      attached to phenol or aniline has same impact on reactivity of Mannich base;
      however, it has opposite influence on oxazine ring stability and equilibrium
      constant. Compared with the phenol-aniline system, electron-donating methyl on
      phenol or aniline increases the charge of nitrogen and oxygen atoms in Mannich
      base. When the methyl group is located at para position of phenol, oxazine ring
      stability increases, and the equilibrium constant climbs, whereas when the methyl
      group is located at the para position of aniline, oxazine ring stability
      decreases, the benzoxazine hydrolysis tends to happen and equilibrium constant is
      significantly low. 

PMID- 25070423
TI  - Anxiety in the management of localised prostate cancer by active surveillance.
AB  - OBJECTIVES: To describe a range of anxieties in men on active surveillance (AS)
      for prostate cancer and determine which of these anxieties predicted health
      related quality of life (HRQL). PATIENTS AND METHODS: In all, 260 men with
      prostate cancer on AS were invited to complete psychological measures including
      the Hospital and Anxiety Depression Scale; the State-Trait Anxiety Inventory
      Trait Scale; the Memorial Anxiety Scale for Prostate Cancer; and the Functional
      Assessment of Cancer Therapy Scale-Prostate. Overall, 86 men with a mean (sd,
      range) age of 65.7 (5.4, 51-75) years returned data, yielding a response rate of
      33%. Outcome measures were standardised psychological measures. Pearson's
      correlations were used to examine bivariate relationships, while regression
      analyses were used to describe predictors of dependent variables. RESULTS: When
      compared with the findings of prior research, the men in our cohort had normal
      levels of general anxiety and illness-specific anxiety and high prostate cancer
      related HRQL. Age, trait anxiety and fear of recurrence (FoR) were significant
      predictors of prostate cancer-related HRQL; trait anxiety and FoR were
      significant predictors of total HRQL. Results should be interpreted in context of
      sample characteristics and the correlational design of the study. CONCLUSIONS:
      Participants reported low levels of anxiety and high HRQL. Trait anxiety and FoR
      were significant predictors of both prostate cancer-related and total HRQL. The
      administration of a short trait-anxiety screening tool may help identify men with
      clinically significant levels of anxiety and those at risk of reduced HRQL.

PMID- 25070422
TI  - Further evaluation of the tropane analogs of haloperidol.
AB  - Previous work from our labs has indicated that a tropane analog of haloperidol
      with potent D2 binding but designed to avoid the formation of MPP(+)-like
      metabolites, such as 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)pyridin
      1-ium (BCPP(+)) still produced catalepsy, suggesting a strong role for the D2
      receptor in the production of catalepsy in rats, and hence EPS in humans. This
      study tested the hypothesis that further modifications of the tropane analog to
      produce compounds with less potent binding to the D2 receptor than haloperidol,
      would produce less catalepsy. These tests have now revealed that while
      haloperidol produced maximum catalepsy, these compounds produced moderate to low
      levels of catalepsy. Compound 9, with the least binding affinity to the D2R,
      produced the least catalepsy and highest Minimum Adverse Effective Dose (MAED) of
      the analogs tested regardless of their affinities at other receptors including
      the 5-HT1AR. These observations support the hypothesis that moderation of the D2
      binding of the tropane analogs could reduce catalepsy potential in rats and
      consequently EPS in man. 

PMID- 25070425
TI  - Identifying keys to success in clinical learning: a study of two
      interprofessional learning environments.
AB  - The aim of this study was to study the intrinsic system behind interprofessional
      clinical learning environments. Two health care units were selected on the basis
      of having received a reward for best clinical learning organization. Interviews
      were carried out with health care staff/clinical supervisors from different
      professions. The interviews were transcribed and analysed according to
      qualitative content analysis, and categories and themes were identified. Analysis
      revealed two different systems of clinical learning environments. In one, the
      interplay between the structural aspects dominated, and in the other, the
      interplay between the cultural aspects dominated. An important similarity between
      the environments was that a defined role for students in the organization and
      interprofessional teamwork around supervision across professional borders was
      emphasized.

PMID- 25070426
TI  - Athletic trainers have a place in interprofessional education and practice.
AB  - Athletic trainers (ATs) are healthcare providers who work in collaboration with
      physicians, nurses, physical therapists and others to provide care to physically
      active individuals. Founded in 1950, the National Athletic Trainers' Association
      (NATA) represents certified ATs and other individuals who support the athletic
      training profession. The Board of Certification (BOC) has the only accredited
      certification program for ATs in USA. It establishes and regularly reviews both
      the standards for the practice of athletic training and the continuing education
      requirements for certified ATs. In order to attain certification, candidates must
      demonstrate successful completion of either a bachelor's degree or master's
      degree program accredited by the Commission on Accreditation of Athletic Training
      Education (CAATE) and pass the BOC certification exam. Currently, there are ~42
      000 ATs practicing in USA, with 48 states who regulate their practice. The
      purpose of this article is to provide a background for the profession of athletic
      training as well as describe and discuss the importance of including ATs in
      interprofessional education and practice initiatives. 

PMID- 25070427
TI  - Interprofessional patient-centred practice in oncology teams: utopia or reality?
AB  - Studies on interprofessional practice usually report professionals' viewpoints
      and document organizational, procedural and relational factors influencing that
      practice. Considering the importance of interprofessional patient-centred (IPPC)
      practice, it seems necessary to describe it in detail in an actual context of
      care, from the perspective of patients, their families and health-care
      professionals. The goal of this study was to describe IPPC practice throughout
      the continuum of cancer care. A qualitative multiple case study was completed
      with two interprofessional teams from a Canadian teaching hospital. Interviews
      were conducted with patients, their families and professionals, and observation
      was carried out. Three themes were illustrated by current team practice:
      welcoming the person as a unique individual, but still requiring the patient to
      comply; the paradoxical coexistence of patient-centred discourse and professional
      centred practice; and triggering team collaboration with the culmination of the
      patient's situation. Several influential factors were described, including the
      way the team works; the physical environment; professionals' and patients'/family
      members' stance on the collaboration; professionals' stance on patients and their
      families; and patients' stance on professionals. Finally, themes describing the
      desired IPPC practice reflect the wish of most participants to be more involved.
      They were: providing support in line with the patient's experience and
      involvement; respecting patients by not imposing professionals' values and goals;
      and consistency and regularity in the collaboration of all members.

PMID- 25070428
TI  - Short-term service trips and the interprofessional team: a perspective from
      Honduras.
AB  - Short-term service trips from the USA annually spend over $250 million dollars to
      provide healthcare to individuals in developing nations. These trips often
      uniquely define goals as related to changes in the host population and overlook
      the valuable benefits potentially incurred by the trip volunteers. The Honduras
      Outreach Medical Brigada Relief Effort utilizes an interprofessional team
      approach to develop the dual goals of improving health and quality of life in
      host communities and improving interprofessional teamwork values and skills among
      participants. This article outlines details of this program, describes on-going
      evaluation work and discusses the interprofessional implications from this
      project.

PMID- 25070429
TI  - Interprofessional education using simulation of an overnight inpatient ward
      shift.
AB  - In healthcare it is rare for professionals to practice together before they
      practice together. Nightmare Night Care is an annual interprofessional voluntary
      event for health sciences students in nursing, medicine and pharmacy to come
      together for a simulated hospital overnight ward shift. The purpose of this study
      was to investigate the interprofessional knowledge, skills and attitudes the
      students learn from this experience. Students responded to surveys before (n =
      45) and after the event (n = 11) regarding their understanding of the goals of
      interprofessional education (IPE), roles and responsibilities of other
      professions, and what they learned from this event. Responses demonstrated that
      students are eager to learn in interprofessional settings and that IPE events may
      aid in building understanding and communication between professions. IPE events
      are an opportunity to allow students to learn about each other; however, they
      must occur frequently, and must include an orientation on role clarification if
      they are to have an effect on changing preconceived stereotypes of the other
      professions. 

PMID- 25070430
TI  - Taking a thermodynamic approach: a conversation with Baron Chanda.

PMID- 25070431
TI  - F-/Cl- selectivity in CLCF-type F-/H+ antiporters.
AB  - Many bacterial species protect themselves against environmental F(-) toxicity by
      exporting this anion from the cytoplasm via CLC(F) F(-)/H(+) antiporters, a
      subclass of CLC superfamily anion transporters. Strong F(-) over Cl(-)
      selectivity is biologically essential for these membrane proteins because Cl(-)
      is orders of magnitude more abundant in the biosphere than F(-). Sequence
      comparisons reveal differences between CLC(F)s and canonical Cl(-)-transporting
      CLCs within regions that, in the canonical CLCs, coordinate Cl(-) ion and govern
      anion transport. A phylogenetic split within the CLC(F) clade, manifested in
      sequence divergence in the vicinity of this ion-binding center, raises the
      possibility that these two CLC(F) subclades might exhibit differences in anion
      selectivity. Several CLC(F) homologues from each subclade were examined for F(
      )/Cl(-) selectivity of anion transport and equilibrium binding. Differences in
      both of these anion-selectivity metrics correlate with sequence divergence among
      CLC(F)s. Chimeric constructs identify two residues in this region that largely
      account for the subclade differences in selectivity. In addition, these
      experiments serendipitously uncovered an unusually steep, Cl(-)-specific voltage
      dependence of transport that greatly enhances F(-) selectivity at low voltage. 

PMID- 25070432
TI  - Tracking S4 movement by gating pore currents in the bacterial sodium channel
      NaChBac.
AB  - Voltage-gated sodium channels mediate the initiation and propagation of action
      potentials in excitable cells. Transmembrane segment S4 of voltage-gated sodium
      channels resides in a gating pore where it senses the membrane potential and
      controls channel gating. Substitution of individual S4 arginine gating charges
      (R1-R3) with smaller amino acids allows ionic currents to flow through the mutant
      gating pore, and these gating pore currents are pathogenic in some skeletal
      muscle periodic paralysis syndromes. The voltage dependence of gating pore
      currents provides information about the transmembrane position of the gating
      charges as S4 moves in response to membrane potential. Here we studied gating
      pore current in mutants of the homotetrameric bacterial sodium channel NaChBac in
      which individual arginine gating charges were replaced by cysteine. Gating pore
      current was observed for each mutant channel, but with different voltage
      dependent properties. Mutating the first (R1C) or second (R2C) arginine to
      cysteine resulted in gating pore current at hyperpolarized membrane potentials,
      where the channels are in resting states, but not at depolarized potentials,
      where the channels are activated. Conversely, the R3C gating pore is closed at
      hyperpolarized membrane potentials and opens with channel activation. Negative
      conditioning pulses revealed time-dependent deactivation of the R3C gating pore
      at the most hyperpolarized potentials. Our results show sequential voltage
      dependence of activation of gating pore current from R1 to R3 and support
      stepwise outward movement of the substituted cysteines through the narrow portion
      of the gating pore that is sealed by the arginine side chains in the wild-type
      channel. This pattern of voltage dependence of gating pore current is consistent
      with a sliding movement of the S4 helix through the gating pore. Through
      comparison with high-resolution models of the voltage sensor of bacterial sodium
      channels, these results shed light on the structural basis for pathogenic gating
      pore currents in periodic paralysis syndromes. 

PMID- 25070434
TI  - Five-year experience of organized colorectal cancer screening in a Swedish
      population - increased compliance with age, female gender, and subsequent
      screening round.
AB  - OBJECTIVE: To evaluate compliance by age, gender, and screening round in the
      population based Stockholm/Gotland colorectal cancer screening programme.
      METHODS: All individuals aged between 60 and 69 living in the counties of
      Stockholm and Gotland (Sweden) have, since 2008, successively been included in a
      colorectal cancer screening programme using biennial faecal occult blood tests
      (Hemoccult(r)). Personal invitations including test kits have been sent to home
      addresses, and individuals with a positive test result have been called to a
      defined clinic for an assessment colonoscopy. Descriptive statistics have been
      used to evaluate different aspects of compliance. RESULTS: Over the five-year
      period 2008-2012, more than 200,000 individuals from nine different birth cohorts
      have been invited, with a compliance rate of approximately 60%, which increased
      by age, female gender, and subsequent screening round. In total, 4,300
      individuals (2.1%) with positive tests were referred to assessment colonoscopy,
      where 213 colorectal cancers were diagnosed. The compliance with the follow-up
      colonoscopies varied by year, and ranged from 85.6-92.4%. CONCLUSION: The strong
      organization of the programme contributed to a high compliance rate, that
      increased by screening round. The lower participation rate among men and among
      individuals at younger ages needs further attention.

PMID- 25070436
TI  - [New concept in weight loss surgery: precise laparoscopic gastric bypass
      surgery].
AB  - Modern weight loss surgery has been transformed from the extensive mode to the
      precision mode. The new concept of precise laparoscopic Roux-en-Y gastric
      bypass(PLRYGB)embodies the advanced ideas of humanistic medicine, evidence-based
      medicine, minimally invasive treatment and so on. The ideal goal is to minimize
      trauma, maximize organ protection, minimize medical cost, and obtain the best
      effect of weight loss. This new concept will have broad prospects and probably
      become the mainstream idea in the field of weight loss surgery. 

PMID- 25070435
TI  - Antioxidant potential of Sutherlandia frutescens and its protective effects
      against oxidative stress in various cell cultures.
AB  - BACKGROUND: Sutherlandia frutescens (L.) R.Br. (SF) is a South African plant that
      is widely used to treat stress, infections, cancer, and chronic diseases, many of
      which involve oxidative stress. The aim of the study was to quantitatively assess
      the antioxidant potential of SF extracts in cell-free system as well as in cell
      lines. METHODS: Dried SF vegetative parts were extracted using six different
      solvents, and the extracts were assessed for total phenolic and flavonoid
      contents, total reducing power, iron chelating capacity, and free radical
      scavenging power, including, scavenging of hydroxyl radicals, superoxide anions,
      nitric oxide, and hydrogen peroxide. We further investigated the freeze-dried hot
      water extract of SF (SFE) to assess its effect against oxidative stress induced
      by tert-butyl hydroperoxide (t-BHP), an organic peroxide. Three different cell
      lines: Chinese hamster ovary (CHO), human hepatoma (HepaRG), and human pulmonary
      alveolar carcinoma (A549) cells, were employed to determine cell viability,
      intracellular reactive oxygen species (ROS) levels, and reduced to oxidized
      glutathione levels (GSH/GSSG). RESULTS: The results indicated that: (1) SF
      extracts have significant antioxidant potential that is dependent upon the nature
      of the extraction solvent and (2) SFE protects against tBHP-induced oxidative
      stress in cells by scavenging ROS and preserving intracellular GSH/GSSG.
      CONCLUSION: Oxidative stress is implicated in a number of disorders, and due to
      the public's concerns about synthetic antioxidants, various natural antioxidants
      are being explored for their therapeutic potential. Our findings support claims
      for S. frutescens being a promising adjunctive therapeutic for oxidative stress
      related health problems.

PMID- 25070437
TI  - [Role and mechanism of duodenal-jejunal bypass in the management of type 2
      diabetes mellitus].
AB  - Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases and
      public health problems. Roux-en-Y gastric bypass (RYGB) can rapidly, effectively
      and sustainably improve glycemic control in morbidly obese patients with T2DM.
      However, the mechanisms of glycemic control after RYGB are still unclear now.
      Duodenal-jejunal bypass (DJB) is an improved RYGB sparing intact stomach, which
      is mainly used to investigate the mechanisms of RYGB to treat T2DM. DJB has also
      been used to treat non-obese T2DM patients. In the present article, we review the
      results and mechanisms of DJB to treat T2DM on the basis of the previous studies
      to further elucidate the mechanisms of RYGB in the management of T2DM. 

PMID- 25070438
TI  - [Application of revisional operation in failure and complication of bariatric
      surgery].
AB  - For the vast majority of morbidly obese patients, surgical treatment remains the
      only effective way proven to maintain weight loss. Currently adjustable gastric
      banding (AGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass(RYGB) are the
      methods which are recognized as safe, reliable, effective for weight loss, and
      has been widely used. Along with the increase in the volume of bariatric
      operations, patients whose primary bariatric operation is not ideal and who need
      revision surgery are also increasing. Weight loss failure and postoperative
      complications are two of the main indications for revisional operation. A series
      of data indicate that revisional operation is an effective treatment for
      unsuccessful weight loss and complications of primary operation. Surgeons should
      choose reasonable, correct operation refer to the initial bariatric operation and
      results. For most patients, the benefits overweigh the risks.

PMID- 25070439
TI  - [Exploration of surgical procedures in the treatment of type 2 diabetes mellitus
      in China].
AB  - The median body mass index(BMI) of patients with type 2 diabetes mellitus(T2DM)
      in China is only 24 kg/m(2) and diabetic diet in China is different from that in
      the Western countries. Currently there are no sufficient weight loss surgery data
      and guidance in China. Therefore, aside from the internationally recognized
      surgical procedures, Chinese surgeons have been trying to find other suitable
      procedures for T2DM. In 2011, operations for treatment of T2DM recommended by the
      International Diabetes Federation(IDF) are as follow: gastric bypass
      surgery(GBP), sleeve gastrectomy(SG), bile pancreatic surgery(BPD), duodenal
      inversion technique(DS) and the adjustable gastric band surgery(AGB). At present,
      the main exploratory surgery procedures in China include: sleeve gastrectomy and
      duodenal-jejual bypass, duodenal-jejual bypass, sleeve gastrectomy and jejual
      ileal bypass, sleeve gastrectomy and ileal interposition, ileal interposition,
      jejunal-ileal bypass, gastric folding technique, gastric folding and banding, and
      other weight loss surgery under endoscopy. Each operation has different
      characteristics, but the optimal surgery for patients with T2DM still needs long
      term follow-up and large sample of multi-center clinical research. We believe
      that under the scientific standardization, surgeons in China will develop the
      most suitable procedures for patients with T2DM. 

PMID- 25070440
TI  - [Precise laparoscopic Roux-en-Y gastric bypass in the treatment of 140 patients
      with obesity and metabolic diseases].
AB  - OBJECTIVE: To investigate the efficacy and safety of precise laparoscopic Roux-en
      Y gastric bypass(LRYGB) in the treatment of obesity and metabolic diseases.
      METHODS: Clinical and follow-up data of obese patients underwent precise LRYGB in
      our department between June 2011 and April 2013 were analyzed retrospectively.
      RESULTS: A total of 140 obese patients were included in this study. All the
      precise LRYGB procedures were successfully performed with no conversion to open
      surgery or perioperative death. Average operation time was (138.0+/-21.3) min,
      postoperative hospital stay was (5.2+/-1.2) d. No severe complications was
      observed. The percentages of excess weight loss in 1, 3, 6, and 12 month after
      operation were (26.4+/-8.6)%, (53.3+/-6.7)%, (75.3+/-7.9)%, (78.5+/-8.5)%,
      respectively. The improvement rates of fatty liver, hyperlipidemia, hypertension
      and type 2 diabetes mellitus were 84.6%(33/39), 92.3%(12/13), 77.3%(17/22) and
      82.4%(14/17). CONCLUSIONS: Precise LRYGB is a modified and optimized traditional
      surgical technique which does not significantly increase the operative time. It
      is safe and feasible. The postoperative weight loss effect is significant and it
      can effectively improve the related co-morbidities.

PMID- 25070441
TI  - [Improvement of islet beta-cell function after sleeve gastrectomy with ileal
      interposition duodenojejunal bypass in non-obese type 2 diabetes mellitus].
AB  - OBJECTIVE: To investigate the improvement of islet beta-cell function after
      sleeve gastrectomy with ileal interposition duodenojejunal bypass operation in
      non-obese type 2 diabetes mellitus. METHODS: Clinical data of 54 non-obese type 2
      diabetes mellitus cases undergoing sleeve gastrectomy with ileal interposition
      duodenojejunal bypass operation in our hospital from March 2009 to October 2011
      were retrospectively analyzed. Fasting glucose, glycosylated hemoglobin(HbA1c),
      fasting insulin, body mass index(BMI), insulin resistance index(HOMA-IR),
      homeostasis model beta-cell function(HOMA-beta), early phase insulin secretion
      index (DelteI30/DelteG30) and area under curve of insulin(AUCINS) were measured
      before operation, and 1, 3, 6, 12, 24 months after operation with standard oral
      glucose tolerance test(OGTT). RESULTS: At 24 months after operation, HbA1c
      decreased from preoperative (8.2+/-0.8)% to postoperative (6.3+/-0.1)%(P<0.01),
      as did the fasting glucose [(9.2+/-0.6) mmol/L vs. (5.9+/-0.5) mmol/L, P<0.01]
      and HOMA-IR (2.1+/-0.6 vs. 0.8+/-0.3, P<0.01). The postoperative BMI was not
      significantly different from the preoperative level. HOMA-beta increased (28.4+/
      9.2 vs. 56.3+/-12.8, P<0.05). DelteI30/DelteG30 increased after surgery (0.8+/
      0.2 vs. 1.8+/-0.7, P<0.01). AUCINS was (42.6+/-17.1) mIU/L, (31.5+/-18.6) mIU/L,
      (34.71+/-12.9) mIU/L, (49.2+/-16.3) mIU/L, (78.3+/-21.7) mIU/L, (74.8+/-15.2)
      mIU/L before operation and at postoperative 1 month, 3 months, 6 months, 12
      months, 24 months, respectively, indicating an increase in AUCINS 6 months later.
      Linear correlation analysis showed that HbA1c was negatively correlated with HOMA
      beta, DelteI30/DelteG30 and AUCINS (r=-0.628, P<0.01; r=-0.571, P<0.01; r=-0.606,
      P<0.01), and positively correlated with HOMA-IR (r=0.784, P<0.01). CONCLUSIONS:
      Sleeve gastrectomy with ileal interposition duodenojejunal bypass can improve
      islet beta cells function. It plays an important role in the surgical treatment
      of diabetes.

PMID- 25070442
TI  - [Learning curve of Roux-en-Y gastric bypass on rats by single operator].
AB  - OBJECTIVE: To analyze the learning curve of gastric bypass procedure on rats
      model by a single operator. METHODS: From June 2013 to September 2013, two groups
      (group A and group B) of rats model were performed gastric bypass surgery, 60
      rats for each group. Each group was divided into 3 stages according to sequence.
      The operative time and postoperative survival rate were compared between A group
      and B group at first, then among stages of each group. RESULTS: There were no
      significant differences between A and B group in operative time and postoperative
      survival rate. However, the operative time significantly decreased in group AII(
      and AIII( compared with AI(, [(78.5+/-2.5) and (73.3+/-1.4) with (127.3+/-3.2)
      min, P<0.01]. The postoperative survival rate was increased in group AII( and
      AIII( than in the group AI(, [75%(15/20) and 85%(17/20) with 30%(6/20), P<0.05].
      All results of 3 stages in group B was similar to group A. CONCLUSION: For an
      efficient and stable rate of successful model establishment, the researcher needs
      to operate about 20 rats to pass the learning curve of gastric bypass procedure.

PMID- 25070443
TI  - [Efficacy analysis of laparoscopic sleeve gastrectomy in treatment of obesity
      with type 2 diabetes mellitus].
AB  - OBJECTIVE: To investigate the efficacy and safety of laparoscopic sleeve
      gastrectomy(LSG) for the treatment of obesity with type 2 diabetes
      mellitus(T2DM). METHODS: Clinical data of 32 obesity patients with T2DM patients
      undergoing LSG from May 2010 to February 2012 in our department were
      retrospectively analyzed. Their body weight indexes (body weight, waist
      circumference, BMI, EWL), blood glucose indexes [glycosylated hemoglobin (HbA1c),
      fasting plasma glucose (FPG), insulin resistance index (HOMA-IR)], and blood
      lipid indexes [total cholesterol, triglyceride, low density lipoprotein
      cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C)] were measured 1,
      3, 6, 12 months after operation and compared with preoperative levels.
      Improvement in complications was observed. RESULTS: All the patients completed
      operation under laparoscopy except 1 case because of abdominal cavity adhesion.
      The average operative time was (115.0+/-19.6) min, and the average blood loss
      (69.0+/-29.7) ml. No operative death, anastomotic leakage, or surgical site
      infection were found. The body weight, waist circumference and BMI at 1, 3, 6,
      and 12 months after surgery were significantly lower(all P<0.05) showing a
      decreasing trend over time. EWL showed significant increasing trend (P<0.05).
      During 12 months of follow-up, no over-low weight was observed. From 1 month
      after surgery, HbA1c, FPG and HOMA-IR decreased significantly (P<0.05). HbA1c and
      FPG maintained stable level at 12 and 6 months after operation respectively. FPG
      of 28 patients returned to normal 3 months after operation. Clinical complete
      remission rate of T2DM was 87.5%(28/32), and clinical partial remission rate was
      12.5%(4/32) at the 12-month follow-up. Serum total cholesterol, triglyceride and
      LDL-C decreased obviously after surgery(P<0.05). CONCLUSION: LSG procedure is a
      safe and effective surgical method in treatment of obesity with T2DM.

PMID- 25070444
TI  - [Prevention and management of complications after laparoscopic gastric bypass
      operation].
AB  - OBJECTIVE: To investigate the prevention and management of complications after
      laparoscopic gastric bypass (LRYGB) operation. METHODS: Clinical data of 82 cases
      (9 cases of simple obesity, 55 of obesity complicated with type 2 diabetes, 18 of
      non-obesity simple type 2 diabetes) undergoing LRYGB in our hospital between May
      2010 to May 2013 were retrospectively analyzed. Cause of complication was
      explored and experience was summarized in order to provide reference to clinical
      practice. RESULTS RESULTS: There was no mortality and re-admission within 30 days
      after procedures. Nine patients developed complications. Punctural injury
      occurred in 1 patient(1.2%) and laparotomy surgery was performed to stop
      bleedind. Hemorrhage was observed in 4 patients(4.9%, one patients had concurrent
      anastomotic ulcer) and was cured by either gastrolavage with solution of
      epinephrine and normal saline or cautery under gastroscope. Anastomotic leakage
      occurred in one patient(1.2%) which was cured by placing nose-gastro tube
      immediately after diagnosis of leakage and total enteral nutrition for one month.
      Anastomotic stricture occurred in 1 patient(1.2%), general peritonitis occurred
      after balloon dilation and laparoscopic repair was performed to repair the
      perforation due to dilation. Gastroplegia occurred in two patients(2.4%) and was
      cured after fasting, gastrointestinal decompression, usage of gastrointestinal
      prokinetic medications and enteral nutrition. All complications were cured at
      last. BMI of all patients dropped in vary extent after a follow up of 19.0
      35.0(29.1+/-5.4) months. CONCLUSIONS: Complication after LRYGB operation may be
      prevented by active preoperative preparation, surgical precision, and intensive
      postoperative care. Even complications occur, the corresponding treatments are
      effective.

PMID- 25070445
TI  - [Impact of the number of lymph nodes dissected on the prognosis of G3 advanced
      gastric cancer].
AB  - OBJECTIVE: To explore the risk factors associated with the prognosis in poorly
      differentiated(G3) advanced gastric cancer (AGC) and the effect of number of
      harvested lymph nodes on the prognosis. METHODS: Clinical data of 484 patients
      with G3 advanced gastric cancer undergoing gastrectomy combined with
      lymphadenectomy in Zhongshan Hospital from December 2002 to October 2007 were
      retrospectively analyzed. The chi(2) test or Fisher's exact probability method
      was used to test measurement data. Survival was calculated using Kaplan-Meier
      method. Clinicopathological factors such as age, invasion depth, number of
      harvested lymph nodes, lymph node metastasis, ratio of metastatic lymph node,
      lymphatic vessels involvement were analyzed using the Cox regression model.
      RESULTS: Number of lymph node dissected, lymph node metastasis, ratio of
      metastatic lymph node and lymphatic vessels involvement were significantly
      affected by groups of 15 lymph node dissected in G3 AGC patients (P<0.05).
      Invasion depth, number of lymph node dissected, lymph node metastasis, ratio of
      metastatic lymph node and lymphatic vessels involvement were significantly
      independent predictors of survival in G3 AGC patients (all P<0.05). Patients with
      at least 20 lymph nodes had a better survival rate than those with less than
      20(P<0.01). CONCLUSIONS: Invasion depth, number of harvested lymph nodes, lymph
      node metastasis, ratio of metastatic lymph node and lymphatic vessels involvement
      are important factors influencing the prognosis of G3 AGC. At least 20 lymph
      nodes should be recommended to ensure the quality of lymphadenectomy for gastric
      cancer.

PMID- 25070446
TI  - [Role of bowel management program in pediatric patients with fecal incontinence].
AB  - OBJECTIVE: To investigate a new bowel management program for children patients
      with fecal incontinence. METHODS: Clinical data of 19 children with fecal
      incontinence undergoing bowel management program in our center between January
      2012 and January 2013 were retrospectively analyzed. The main outcome measure was
      clinical efficacy of this program. RESULTS: Fifteen out of 19 cases were genuine
      fecal incontinence and required continuous treatment by enema. The other 4 cases
      were false fecal incontinence. After treatment with this program, stool dirty and
      constipation were improved in genuine incontinence. Two cases of false continence
      could control defecation independently by oral administration of antispasmodic
      drug. Two cases of false continence were cured and did not need medical
      interference. CONCLUSIONS: Bowel management program is an effective treatment for
      pediatric patients with fecal incontinence. The key of success is maintenance of
      perianal hygiene for 24 hours by continual adjustment of the elements and volumes
      of enemas.

PMID- 25070448
TI  - [Subtotal colectomy with cecorectal end-side anastomosis in the treatment of slow
      transit constipation].
AB  - OBJECTIVE: To study the feasibility of subtotal colectomy with cecorectal end
      side anastomosis for slow transit constipation. METHODS: Retrospective analysis
      was performed on 23 patients with colon slow transit constipation treated by
      subtotal colectomy with cecorectal end-side anastomosis in our department from
      March 2006 to April 2013. The main measure outcome was the curative effect on
      constipation by this type of surgery. RESULTS: Twenty-three patients were
      successfully treated. Anastomotic leakage occurred in one case, and urinary
      retention in 1 case, while no anastomotic stricture, abdominal bleeding,
      abdominal hernia, incontinence and other complications occurred. During follow-up
      of 2 months to 7 years, defecation frequency was 1-4 times a day with no need of
      antidiarrheal agents. Each time of defecation was less than 5 min. All the
      patients had no recurrence of constipation. CONCLUSION: Subtotal colectomy with
      cecorectal end-side anastomosis can be used to treat colon slow transit
      constipation, while accurate preoperative evaluation and strict indications for
      the surgery is the key to success.

PMID- 25070447
TI  - [Impact of microbial immune enteral nutrition on postoperative insulin resistance
      and infectious complication of patients with abdominal infection].
AB  - OBJECTIVE: To investigate the effect of microbial immune enteral nutrition
      composed of probiotics, deep sea fish oil, glutamine and nutrison on
      postoperative immune status, insulin resistance and infectious complication
      morbidity in patients with abdominal infection. METHODS: From September 2010 to
      April 2013 in Shandong Liaocheng City Hospital, 96 patients with upper
      gastrointestinal perforation were prospectively randomized into the treatment
      group (microbial immune enteral nutrition, n=48) and the control
      group(conventional enteral nutrition, n=48). Number of T cell subsets (CD3(+),
      CD4(+), CD8(+), CD4(+)/CD8(+)) and natural killer (NK) cell, procalcitonin (PCT),
      fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index
      (InHOMA-IR) calculated by the homeostasis model assessment(HOMA) were detected
      before operation and on days 3 and 7 after operation and compared between the two
      groups. The incidence of postoperative infectious complication was collected and
      compared as well. RESULTS: There were no significant differences in immune
      indexes and insulin resistance-associated indexes between the two groups before
      operation and on the day 3 after operation(all P>0.05). On postoperative day 7,
      CD4(+), CD4(+)/CD8(+) and NK cells in treatment group were significantly higher
      than those in control group [(39.1+/-4.3)% vs. (30.1+/-5.7)%, P=0.043; 1.76+/
      0.21 vs. 1.36+/-0.12, P=0.038; (19.3+/-4.8)% vs. (13.3+/-3.2)%, P=0.032], while
      FINS, lnHOMA-IR and PCT in treatment group were significantly lower than those in
      control group [(7.3+/-1.7) mU/L vs. (10.2+/-2.1) mU/L, P=0.041; 0.60+/-0.05 vs.
      0.88+/-0.06, P=0.039; (0.12+/-0.07) MUg/L vs. (0.35+/-0.12) MUg/L, P=0.028].
      Postoperative infectious complication morbidity was significantly lower in
      treatment group as compared to control group [18.8%(9/48) vs. 39.6%(19/48),
      P=0.025]. CONCLUSION: Microbial immune enteral nutrition composed of probiotics,
      deep sea fish oil, glutamine and nutrison can improve the immune status, decrease
      the level of insulin resistance, and reduce the incidence of postoperative
      infectious complication for patients with abdominal infection due to upper
      gastrointestinal perforation.

PMID- 25070449
TI  - [Application of adaptive iterative dose reduction technique in CT enterography in
      diagnosing Crohn disease].
AB  - OBJECTIVE: To evaluate the application of low-dose CT enterography with adaptive
      iterative dose reduction(AIDR) technique in diagnosing Crohn's disease. METHODS:
      Retrospective analysis was performed on 26 patients diagnosed as Crohn's disease
      by the multidisciplinary team in our hospital. Low-dose CT enterography with 640
      slice MDCT was performed on these 26 patients using adaptive iterative dose
      reduction(AIDR) technique. Characteristics of Crohn's disease in CT enterography
      images were independently analyzed by two radiologists who were experienced in
      Crohn's disease with calculating the total radiation dosage. RESULTS: The
      radiation dosage of 26 patients ranged from 5.58 to 12.90 [mean (9.00+/-2.00)]
      mSv, which was lower than conventional scan (around 15 mSv) known from the
      literatures. According to the images of CT enterography of 26 cases, bowel wall
      thickening with abnormal enhancement and lymphadenectasis were found in 25 cases
      with total 109 segmental bowel wall thickening. Among 25 thickening cases,
      enterostenosis was found in 16 cases, stratification enhancement in 12 cases and
      comb sign in 14 cases. Besides, it was found that 8 cases with hyperdense fat on
      the mesenteric side, 7 cases with intestinal fistula, 6 cases with abdominal
      cavity abscess, and 3 cases with anal fistula. CONCLUSION: CT enterography of
      Crohn's disease with adaptive iterative dose reduction technique is an effective
      method to evaluate Crohn's disease without compromising image quality with
      reduced radiation dosage.

PMID- 25070450
TI  - [Risk factors for delayed gastric emptying after gastrectomy: a meta analysis].
AB  - OBJECTIVE: To explore the risk factors of delayed gastric emptying after
      gastrectomy. METHODS: Meta-analysis was performed to screen risk factors of
      delayed gastric emptying after gastrectomy based on 19 associated articles
      published from 2003 to 2013. RESULTS: Gender, operative time, blood loss during
      operation, surgical settings(emergency, elective surgery), radical surgery were
      not significantly different between two groups for delayed gastric emptying (all
      P>0.05). Age more than or equal to 60 years [combined odds ratio(OR)=1.65, 95%
      confidence interval(CI):1.31-2.09, P<0.01], preoperative gastrointestinal
      obstruction(combined OR=3.72, 95%CI:3.05-4.55, P<0.01), Billroth-II( (combined
      OR=3.35, 95%CI:2.72-4.13, P<0.01), anemia(combined OR=1.48, 95%CI:1.08-2.02,
      P=0.01), intra-abdominal complication (combined OR=2.41, 95%CI:1.77-3.29,
      P<0.01), perioperative blood glucose greater than 8 mmol/L(combined OR=2.64,
      95%CI:2.00-3.49, P<0.01), postoperative albumin levels lower than 30 g/L
      (combined OR=2.13, 95%CI:1.62-2.79, P<0.01), use of analgesics pump after
      operation (combined OR=1.74, 95%CI:1.33-2.26, P<0.01), having adverse
      psychological reactions (combined OR=5.94, 95%CI:1.79-19.73, P=0.004) were risk
      factors affecting delayed gastric emptying. CONCLUSION: Age more than or equal to
      60, preoperative gastrointestinal obstruction, perioperative blood glucose
      greater than or equal to 8 mmol/L, postoperative albumin levels less than 30 g/L,
      Billroth-II(, anemia, intra-abdominal complication, using pain pump after
      operation, having adverse psychological reactions are risk factors affecting
      delayed gastric emptying after gastrectomy.

PMID- 25070451
TI  - [Clinical observation of abdominal regional fluorouracil implants in advanced
      gastric cancer patients during operation].
AB  - OBJECTIVE: To investigate the postoperative adverse events and survival of
      patients with sustained-released fluorouracil implanted during operation.
      METHODS: Data of 124 patients with advanced gastric cancer undergoing radical
      operation in Tianjin Medical University Cancer Institute and Hospital from
      January 2007 to January 2009 were analyzed retrospectively. All the patients were
      divided into two groups according to whether intra-operative fluorouracil was
      implanted or not. The treatment group(n=64) was implanted with fluorouracil in
      abdominal cavity after radical resection. The control group(n=60) did not receive
      fluorouracil implant in abdominal cavity after radical resection. Abdominal
      drainage fluid, temperature and adverse events within 15 postoperative days and 3
      year survival were observed and compared between the two groups. RESULTS:
      Pathological findings of the two groups were similar. No statistical
      significances existed in abdominal drainage fluid, temperature and adverse events
      within 15 postoperative days(P>0.05). The 3-year survival rate was higher in
      treatment group(64.3% vs. 42.4%, P=0.018). CONCLUSION: Intra-operative sustained
      released fluorouracil implants are safe and tolerable, and can improve the
      survival rate of patients with advanced gastric cancer.

PMID- 25070452
TI  - [Clinical study of autologous cytokine-induced killer cells combined with XELOX
      regimen in the treatment of senile advanced gastric cancer].
AB  - OBJECTIVE: To evaluate the efficacy and safety of autologous cytokine-induced
      killer (CIK) cell t combined with XELOX regimen in treatment of senile advanced
      gastric cancer. METHODS: Forty-six cases of senile advanced gastric cancer
      patients with a mean age of 70 years were prospectively divided into two groups
      according to individual acceptance of CIK cells: 25 patients receiving autologous
      CIK cell treatment combined with XELOX regimen (trial group) and 21 patients
      receiving simple chemotherapy (control group). Patients in CIK group were matched
      to those in control group by sex, ages, KPS ranking scores, histological type,
      pathological grade, and clinical stage. Immune reaction, adverse reaction, time
      to progression (TTP) and overall survival (OS) were evaluated. RESULTS: Host
      immune function was increased (P<0.05) and the adverse reaction was decreased in
      patients of trial group as compared to control group. There were no significant
      differences in response rate (RR)(33.3% vs. 23.1%, P>0.05), disease control rate
      (DCR)(86.7% vs. 80.8%, P>0.05) between the two groups. TTP (4.8 months vs. 3.1
      months, P<0.05) and OS (7.1 months vs. 5.9 months, P<0.05) in trial group were
      significantly improved as compared to control group. CONCLUSION: Autologous CIK
      cells combined with XELOX regimen can increase immune function, improve clinical
      efficacy, decrease adverse reaction and prolong OS for senile patients with
      advanced gastric cancers.

PMID- 25070453
TI  - [Comparison of efficacy and safety between two kinds of injection therapy in the
      treatment of I-II degree rectal prolapse].
AB  - OBJECTIVE: To explore the safety and efficacy of Shaobei injection in the
      management of I(-II( degree rectal prolapse. METHODS: A total of 80 patients
      eligible for the inclusion criteria were divided into 2 groups: 40 patients in
      the treatment group (treated with Shaobei injection) and 40 cases in the control
      group (treated with Xiaozhiling) respectively. The short-term efficacy was
      identified by the length of rectal prolapse and the depth of rectocele
      demonstrated by the defecography while the long-term efficacy was evaluated by
      the length of rectal prolapse. In addition, the safety was assessed by the
      occurrence of postoperative complications. RESULTS: The variation of the lengths
      of rectal prolapse and the depth of rectocele demonstrated by the defecography at
      the sixth month follow up in the two groups did not reach significant difference
      (P>0.05). After 2 year follow up, 37 patients (92.5%) in the treatment group and
      35 cases(87.5%) in the control group was cured. Therefore, there was no
      significant difference in the long term efficacy between the two groups (P>0.05).
      The adverse events in the therapy group(10%) was less than that in the control
      group (45%)(P<0.01). CONCLUSIONS: Shaobei injection in the management of I(-II(
      degree rectal prolapse has a similar efficacy of short-term and long-term higher
      safety compared to Xiaozhiling injection.

PMID- 25070454
TI  - [Inflammation promotes the development of colitis-associated colorectal cancer].
AB  - OBJECTIVE: To confirm that the severity of inflammation can promote the colitis
      associated colorectal cancer(CAC) and explore the function of STAT3 signal
      pathway in CAC. METHODS: Mutagenic agent azoxymethane(AOM) and pro-inflammatory
      agent dextran sodium sulfate salt (DSS) were used to develop a mouse model of
      CAC. By changing the concentration of DSS (0, 1% and 2% respectively), the mouse
      model with different extent of severity of inflammation was developed and the
      risk of carcinogenesis among these groups was compared. The expression of STAT3
      signal pathway was detected by immunohistochemistry staining. RESULTS: In the
      evaluation of inflammatory severity, disease activity index, histopathological
      inflammation scores and the expression of pro-inflammation chemokines such as TNF
      alpha, IL-6 and IL-12 in the higher inflammatory response group were higher than
      that in the lower inflammatory response group. The incidence of colorectal tumor
      was 100%(12/12) in the higher inflammatory response group and the incidence of
      colorectal tumor was 58.3%(7/12) in the lower inflammatory response group, and
      the difference between these two group was statistically significant (P<0.05).
      The multiplicity(number of tumors/colon) was 12.5+/-0.5 in the higher
      inflammatory response group and the multiplicity was 6.6+/-1.0 in the lower
      inflammatory response group, and the difference between these two groups was
      statistically significant (P<0.001). The tumor load(sum of tumor diameters per
      mouse) in the higher inflammatory response group was 44.2+/-2.4 mm and that in
      the lower inflammatory response group was only 18.7+/-2.7 mm, and the difference
      between these two groups was statistically significant (P<0.0001). Moreover, the
      expression of p-STAT3 (Tyr705) was higher in colitis tissue of the higher
      inflammatory response group than that of the lower inflammatory response group.
      CONCLUSIONS: Inflammation can promote the colitis-associated CAC. And the
      activation of STAT3 signal pathway may promote the development of CAC.

PMID- 25070455
TI  - [Effect of mesenteric lymph drainage on intestinal barrier function in rats with
      severe intraperitoneal infection].
AB  - OBJECTIVE: To investigate the effect of mesenteric lymph drainage on intestinal
      barrier function in severe intraperitoneal infection (SII). METHODS: Thirty
      healthy male Wistar rats were randomly divided into 3 groups(model group,
      drainage group and control group). SII model rats were prepared by injecting
      E.coli intraperitoneally. Rats in drainage group rats underwent mesentery
      lymphatic duct ligation and drainage 2 hours after model induction, and those in
      control group received equal amount of 10% BaSO4 nutrient broth injection
      intraperitonerally. Six hours after model induction, rats were sacrificed. The
      intestinal samples were collected for pathology analysis and content of DAO and
      concentration of TNF-alpha, IL-6. Content of D-lactate in blood plasma was
      detected. RESULTS: Under light microscopy, ileum mucosa tissue structure of model
      group was disordered. Under transmission electron microscopy, intestinal mucosal
      epithelial cells of model group swelled obviously, close connection was
      destructed, and early apoptosis cells occurred. After mesentery lymph drainage,
      intestinal mucosa tissue structure was improved obviously, endoplasmic reticulum
      and mitochondria of epithelium swelled mildly. The contents of intestinal tissue
      DAO in drainage group, model group and control group were (5.9+/-0.4) U/L, (3.0+/
      0.1) U/L and (18.3+/-2.1) U/L respectively. There was significant difference
      among groups (P<0.05). Compared with control group [(45.4+/-37.9) MUg/L], the
      plasma content of D-lactate in model group [(256.0+/-177.2) MUg/L] increased
      significantly (P<0.05). The plasma content of D-lactate in drainage group
      [(136.9+/-21.5) MUg/L] was not significantly different compared with model group
      (P>0.05), but was significantly higher compared to control group (P<0.05).
      Compared with control group, model group had significantly higher levels of TNF
      alpha [(3431.3+/-23.9) ng/L vs. (2730.0+/-408.7) ng/L] and IL-6 [(86.3+/-1.6)
      ng/L vs. (30.2+/-0.9) ng/L] (P<0.05), while the TNF-alpha was (2653.2+/-324.1)
      ng/L, and the IL-6 was (50.9+/-0.7) ng/L in drainage group, which were
      significantly lower compared with model group (P<0.05). CONCLUSION: Mesenteric
      lymph drainage can obviously improve intestinal barrier function in severe
      intraperitoneal infection and may play a protective role in intestinal mucosa.

PMID- 25070456
TI  - [Expression and significance of Beclin-1 in vasculogenic mimicry formation of
      gastric cancer].
AB  - OBJECTIVE: To explore the effect and mechanism of autophagy specific gene Beclin
      1 in gastric cancer cell SGC7901 on vasculogenic mimicry (VM) forming ability.
      METHODS: Plasmid vectors with and without integrated shRNA were transfected
      respectively into SGC7901 cell line (Beclin1-inhibited group and negative control
      group). Simple SGC7901 cell line was used as blank group. RT-PCR and Western blot
      were performed to examine the expression of Beclin-1 in 3 groups. Culture was
      used to construct the VM model in vitro. Different VM forming ability was
      measured and genes (beclin-1, notch-1) expression of each group was detected
      before and after VM formation. RESULTS: Beclin-1 and notch-1 expression increased
      significantly in the process of VM forming. When beclin-1 was inhibited, the
      formation of VM was limited and VM formative genes expression decreased. As
      compared to cells of negative control group, those of Beclin1-inhibited group had
      less number of VM forming cellular tube-like construction (15.4+/-1.1 vs. 37.8+/
      1.9, P<0.05), shorter length of such construction [(316.8+/-24.6) mm vs. (385.1+/
      14.2) mm, P<0.05], and less crossing point (11.6+/-1.1 vs. 27.2+/-1.1, P<0.05).
      CONCLUSIONS: Beclin-1 can promote VM formation through maintaining stable
      expression of gastric cancer cell VM regulating genes. Beclin-1 inhibition may be
      a new target for gastric cancer gene therapy.

PMID- 25070457
TI  - [Research progress in mechanisms by which bariatric surgery improves metabolism].
AB  - Bariatric surgery is the most effective treatment for obesity and its
      comorbidities, but mechanisms of bariatric surgery remain unknown. In addition to
      volume restriction and malabsorption, gut hormones, bile acids, adipokines,
      intestinal microbiome and central nervous system may be the potential mechanisms.

PMID- 25070458
TI  - [Possible mechanisms of Roux-en-Y gastric bypass treatment for type 2 diabetes
      mellitus].
AB  - Roux-en-Y gastric bypass(RYGB) is a classic procedure for the treatment of type 2
      diabetes mellitus (T2DM), but it remains unclear why this procedure works. There
      might be several mechanisms that RYGB works through to treat T2DM, including
      calorie restriction and malabsorption, improvement of insulin resistance and beta
      cell functions, and altered secretion of gastrointestinal hormones. Altered
      levels of adipokines and serum bile acids might also play a role after RYGB.
      Future researches should concentrate on the exact mechanism of the altered
      hormone levels after RYGB, and whether different methods of gastrointestinal
      tract reconstruction could lead to various hormone levels. 

PMID- 25070459
TI  - Assessing the hodgepodge of non-mapped reads in bacterial transcriptomes: real or
      artifactual RNA chimeras?
AB  - BACKGROUND: RNA sequencing methods have already altered our view of the extent
      and complexity of bacterial and eukaryotic transcriptomes, revealing rare
      transcript isoforms (circular RNAs, RNA chimeras) that could play an important
      role in their biology. RESULTS: We performed an analysis of chimera formation by
      four different computational approaches, including a custom designed pipeline, to
      study the transcriptomes of M. pneumoniae and P. aeruginosa, as well as mixtures
      of both. We found that rare transcript isoforms detected by conventional
      pipelines of analysis could be artifacts of the experimental procedure used in
      the library preparation, and that they are protocol-dependent. CONCLUSION: By
      using a customized pipeline we show that optimal library preparation protocol and
      the pipeline to analyze the results are crucial to identify real chimeric RNAs.

PMID- 25070460
TI  - Use of cardiac implantable electronic devices in older adults with cognitive
      impairment.

PMID- 25070461
TI  - A novel picoliter droplet array for parallel real-time polymerase chain reaction
      based on double-inkjet printing.
AB  - We developed and characterized a novel picoliter droplet-in-oil array generated
      by a double-inkjet printing method on a uniform hydrophobic silicon chip
      specifically designed for quantitative polymerase chain reaction (qPCR) analysis.
      Double-inkjet printing was proposed to efficiently address the evaporation issues
      of picoliter droplets during array generation on a planar substrate without the
      assistance of a humidifier or glycerol. The method utilizes piezoelectric inkjet
      printing equipment to precisely eject a reagent droplet into an oil droplet,
      which had first been dispensed on a hydrophobic and oleophobic substrate. No
      evaporation, random movement, or cross-contamination was observed during array
      fabrication and thermal cycling. We demonstrated the feasibility and
      effectiveness of this novel double-inkjet method for real-time PCR analysis. This
      method can readily produce multivolume droplet-in-oil arrays with volume
      variations ranging from picoliters to nanoliters. This feature would be useful
      for simultaneous multivolume PCR experiments aimed at wide and tunable dynamic
      ranges. These double-inkjet-based picoliter droplet arrays may have potential for
      multiplexed applications that require isolated containers for single-cell
      cultures, single molecular enzymatic assays, or digital PCR and provide an
      alternative option for generating droplet arrays on planar substrates without
      chemical patterning. 

PMID- 25070464
TI  - Multi-centre retrospective analysis of anaphylaxis during general anaesthesia in
      the United Kingdom: aetiology and diagnostic performance of acute serum tryptase.
AB  - This is the first multi-centre retrospective survey from the United Kingdom to
      evaluate the aetiology and diagnostic performance of tryptase in anaphylaxis
      during general anaesthesia (GA). Data were collected retrospectively (2005-12)
      from 161 patients [mean +/- standard deviation (s.d.), 50 +/- 15 years] referred
      to four regional UK centres. Receiver operating characteristic curves (ROC) were
      constructed to assess the utility of tryptase measurements in the diagnosis of
      immunoglobulin (Ig)E-mediated anaphylaxis and the performance of percentage
      change from baseline [percentage change (PC)] and absolute tryptase (AT)
      quantitation. An IgE-mediated cause was identified in 103 patients (64%);
      neuromuscular blocking agents (NMBA) constituted the leading cause (38%) followed
      by antibiotics (8%), patent blue dye (6%), chlorhexidine (5%) and other agents
      (7%). In contrast to previous reports, latex-induced anaphylaxis was rare (0.6%).
      A non-IgE-mediated cause was attributed in 10 patients (6%) and no cause could be
      established in 48 cases (30%). Three serial tryptase measurements were available
      in 34% of patients and a ROC analysis of area under the curve (AUC) showed
      comparable performance for PC and AT. A >= 80% PPV for identifying an IgE
      mediated anaphylaxis was achieved with a PC of >141% or an AT of >15.7 mg/l.
      NMBAs were the leading cause of anaphylaxis, followed by antibiotics, with latex
      allergy being uncommon. Chlorhexidine and patent blue dye are emerging important
      health-care-associated allergens that may lead to anaphylaxis. An elevated acute
      serum tryptase (PC >141%, AT >15.7 mg/l) is highly predictive of IgE-mediated
      anaphylaxis, and both methods of interpretation are comparable.

PMID- 25070465
TI  - Prophylactic red blood cell exchange may be beneficial in the management of
      sickle cell disease in pregnancy.
AB  - BACKGROUND: Sickle cell disease (SCD) is associated with chronic hemolysis and
      painful episodes. Pregnancy accelerates sickle cell complications, including
      prepartum and postpartum vasoocclusive crisis, pulmonary complications, and
      preeclampsia or eclampsia. Fetal complications include preterm birth and its
      associated risks, intrauterine growth restriction, and a high rate of perinatal
      mortality. The purpose of this study was to evaluate pregnancy outcomes in
      patients with SCD who underwent planned preventive red blood cell exchange
      (RBCX). STUDY DESIGN AND METHODS: We retrospectively evaluated the complications
      of SCD in 37 pregnant patients. Patients with SCD who had undergone prophylactic
      RBCX were compared with a control group who had not undergone RBCX during
      pregnancy. RESULTS: Forty-three exchange procedures were performed in 24
      patients. The control group comprised 13 patients with a mean age of 27.4 +/- 3.3
      years who had not undergone RBCX during pregnancy. Four of the five patients who
      developed a vasoocclusive crisis died. There was a significant difference in
      maternal mortality between the study and control groups (p = 0.011). There was
      also a significant difference in the incidence of vasoocclusive crisis between
      the study and control groups. One fetal death occurred in the 20th gestational
      week in a patient in the control group, although there were no postpartum
      complications in either the babies or the mothers in the control group.
      CONCLUSION: This study has demonstrated that prophylactic RBCX during pregnancy
      is a feasible and safe procedure for prevention of complications. Given the
      decrease in the risks of transfusion, RBCX warrants further study.

PMID- 25070466
TI  - Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in
      children.
AB  - INTRODUCTION: Ketone formation is a normal response when hypoglycemia occurs.
      Since the majority of children with recurrent hypoglycemia cannot be diagnosed
      with a known endocrine or metabolic disorder on a critical sample, ketotic
      hypoglycemia has been described as the most common cause of low blood glucose
      concentrations in children. Critical samples, however, will miss the ketotic
      forms of glycogen storage disease (GSD), which present with elevated ketones,
      hypoglycemia, and normal hormonal concentrations. RESULTS: A total of 164
      children (96 boys, 68 girls) were enrolled in the study. Prediction of
      pathogenicity of DNA changes using computer modeling confirmed pathology in 20
      individuals [four GSD 0, two GSD VI, 12 GSD IX alpha, one GSD IX beta, one GSD IX
      gamma] (12%). Boys were most likely to have changes in the PHKA2 gene, consistent
      with GSD IX alpha, an X-linked disorder. CONCLUSIONS: Mutations in genes involved
      in glycogen synthesis and degradation were commonly found in children with
      idiopathic ketotic hypoglycemia. GSD IX is likely an unappreciated cause of
      ketotic hypoglycemia in children, while GSD 0 and VI are relatively uncommon. GSD
      IX alpha should particularly be considered in boys with unexplained hypoglycemia.

PMID- 25070467
TI  - Associations of early life and sociodemographic factors with menarcheal age in
      European adolescents.
AB  - Early menarche has been associated with adult overweight, cardiovascular risk
      factors, and other diseases. Little is known about the determinants of menarcheal
      age (MA). Therefore, the main aim of this study was to examine the associations
      between early life programming factors and menarcheal age in European
      adolescents. Secondly, the influence of sociodemographical factors on menarcheal
      age was also studied. A total of 1,069 European girls from the HELENA cross
      sectional study, aged 12.5-17.5 years, were included in this study. Using
      multilevel linear regression models, a possible association between birth weight
      and length, ponderal index at birth, gestational age, duration of exclusive
      breastfeeding, and menarcheal age was examined. Associations between geographical
      gradient, number of siblings, physical activity (PA), dietary factors, and
      menarcheal age were also examined. After adjustment, menarcheal age was
      positively associated with birth weight and length (p = 0.01 and p = 0.01).
      CONCLUSION: These findings confirm that birth weight and length may have a
      programming effect on menarcheal age. Next to this finding, sociodemographic
      factors were not associated with menarcheal age.

PMID- 25070468
TI  - A systematic review of treatments for anxiety in youth with autism spectrum
      disorders.
AB  - This study systematically examined the efficacy and safety of
      psychopharmacological and non-psychopharmacological treatments for anxiety in
      youth with autism spectrum disorders (ASD). Four psychopharmacological, nine
      cognitive behavioral therapy (CBT), and two alternative treatment studies met
      inclusion criteria. Psychopharmacological studies were descriptive or open label,
      sometimes did not specify the anxiety phenotype, and reported behavioral
      activation. Citalopram and buspirone yielded some improvement, whereas
      fluvoxamine did not. Non-psychopharmacological studies were mainly randomized
      controlled trials (RCTs) with CBT demonstrating moderate efficacy for anxiety
      disorders in youth with high functioning ASD. Deep pressure and neurofeedback
      provided some benefit. All studies were short-term and included small sample
      sizes. Large scale and long term RCTs examining psychopharmacological and non
      psychopharmacological treatments are sorely needed. 

PMID- 25070469
TI  - College students' perceptions of peers with autism spectrum disorder.
AB  - Little is known about peer attitudes toward college students with autism spectrum
      disorder (ASD). Affective, behavioral, and cognitive attitudes toward vignette
      characters displaying behaviors characteristic of ASD were examined among 224
      four-year university students who were randomly assigned to one of three labeling
      conditions for the primary vignette characters: high functioning autism (HFA),
      typical college student, or no label. Students in the HFA label condition
      reported more positive behavioral and cognitive attitudes toward the vignette
      characters than students in the no label condition. Male students and students
      with lower scores on the Broad Autism Phenotype Questionnaire reported more
      positive attitudes across study conditions. These experimental results suggest
      that knowledge of a diagnosis might improve attitudes toward college students
      with ASD. 

PMID- 25070470
TI  - Indicators of intellectual disabilities in young children with autism spectrum
      disorders.
AB  - No agreement has been reached yet on the co-occurrence of Intellectual Disability
      (ID) and Autism Spectrum Disorders (ASD) in young children. This study describes
      the clinical profiles of 253 children with ASD between 30 and 65 months old, on
      IQ and adaptive behaviors, prior to their entry in an early behavioral
      intervention program. Results showed that 36.8% of the children met the criteria
      for ID, with 60.2% of these in the mild range (IQ 50-69) and 39.8% in the
      moderate range (IQ 35-49). ID profiles were similar for boys and girls.
      Intellectual and adaptive behavior profiles are described as well as their links
      to various socioeconomic factors.

PMID- 25070471
TI  - Change in autism symptoms and maladaptive behaviors in adolescence and adulthood:
      the role of positive family processes.
AB  - Little is known about outcomes for individuals with autism spectrum disorders
      (ASD) into adulthood. Several characteristics of individuals with ASD predict
      long-term outcomes, and the family environment may also play a role. The present
      study uses a prospective, longitudinal design to describe and predict
      trajectories of autism symptoms and maladaptive behaviors over 8.5 years in a
      large, community-based sample of adolescents and adults with ASD. Overall, autism
      symptoms and maladaptive behaviors were observed to improve over the study
      period. Above and beyond the adult's gender, age, and level of intellectual
      disability, greater improvements were associated with higher levels of maternal
      praise (based on maternal speech samples) and higher quality mother-child
      relationships. Implications for future research and intervention are discussed.

PMID- 25070472
TI  - Increased Hs-CRP/adiponectin ratio is associated with increase carotid intima
      media thickness.
AB  - BACKGROUND: High sensitivity C-reactive protein (Hs-CRP) and adiponectin (APN)
      are two critical cytokines and exert inverse effects on atherosclerosis
      initiation and progression. The purpose of our study was to investigate the value
      of Hs-CRP and ANP ratio (Hs-CRP/APN ratio) on evaluating atherosclerosis
      progression. METHOD: One hundred sixty consecutive participants underwent carotid
      intima-media thickness (CIMT) measured by ultrasound were enrolled and drawn
      fasting blood samples for plasma levels Hs-CRP and APN, serum levels of lipid
      profiles and fasting blood glucose evaluation. Other anthropometrics and clinical
      status were collected by questionnaire. All participants were divided into 4
      groups according to the baseline Hs-CRP/APN ratio and underwent CIMT measurement
      every 6 months. CIMT increment and composite cardiovascular endpoints were
      compared after 24 months' follow-up. RESULTS: At baseline, body mass index (BMI),
      smoking, diabetic mellitus, usage of statins, Hs-CRP and APN independently
      correlated with Hs-CRP/APN ratio as analyzed by spearman rank correlation.
      Smoking, serum level of LDL-C, plasma level of Hs-CRP and Hs-CRP/APN ratio were
      positively correlated with CIMT while usage of statins and plasma level of APN
      were negatively correlated with CIMT as analyzed by multiple linear regression
      analysis. After 24 months' follow-up, the progression of CIMT was the most
      prominent in the fourth quartile of baseline Hs-CRP/APN ratio. In addition, the
      incidence of composite cardiovascular endpoint was also higher in the fourth
      quartile as compared to the other 3 lower quartiles. CONCLUSION: Hs-CRP/APN ratio
      was a useful predictor to discriminate subjects who were at increased risk of
      atherosclerosis progression.

PMID- 25070473
TI  - Capillary electrophoretic methods for the screening and determination of
      pharmacologic adulterants in herbal-based pharmaceutical formulations.
AB  - This review aims to describe the CE methods utilized for the determination of
      adulterants in herbal-based formulations marketed for different therapeutic
      purposes. The CE methods for screening and determination of pharmacologic
      adulterants are reviewed on the basis of the CE techniques and their detection
      methods. CZE and MEKC methods coupled to optical (UV), capacitively coupled
      contactless conductivity, and MS detection modes are discussed and reviewed.
      Worldwide adulteration cases related to pharmaceutical formulations containing
      herbs as the main active products are presented covering all the works published
      in the last four decades. 

PMID- 25070474
TI  - A honeycomb-layered Na3Ni2SbO6: a high-rate and cycle-stable cathode for sodium
      ion batteries.
AB  - A honeycomb layered Na3Ni2SbO6 is synthesized as a cathode for sodium-ion
      batteries. This new host material exhibits a high capacity of 117 mA h g(-1), a
      remarkable cyclability with 70% capacity retention over 500 cycles at a 2C rate,
      and a superior rate capability with >75% capacity delivered even at a very high
      rate of 30 C (6000 mA g(-1)). These results open a new perspective to develop
      high-capacity and high-rate Na-ion batteries for widespread electric-energy
      storage applications.

PMID- 25070476
TI  - Large-scale finite element analysis of human cancellous bone tissue micro
      computer tomography data: a convergence study.
AB  - The complex geometry of cancellous bone tissue makes it difficult to generate
      finite element (FE) models. Only a few studies investigated the convergence
      behavior at the tissue scale using Cartesian meshes. However, these studies were
      not conducted according to an ideal patch test and the postelastic convergence
      behavior was not reported. In this study, the third principal strain and stress,
      and the displacement obtained from human micro finite element (microFE) models of
      lower resolutions were compared against the model of 19.5 MUm as a reference,
      representing the original spatial resolution of microCT data. Uni-axial
      compression simulations using both linear-elastic and nonlinear constitutive
      equations were performed. The results showed a decrease in percentage difference
      in all three values as the element size decreased, with the displacement
      converging the fastest among the three. Simulations carried out using a nonlinear
      constitutive equation however, failed to show convergence for the third principal
      strains and stresses. It was concluded that at the tissue level, Cartesian meshes
      of human cancellous bone tissue were able to reach a converged solution in all
      three parameters investigated for linear simulation and only in displacement for
      nonlinear simulation. These parameters can be used as references in the future
      for studies in local biomechanical behavior of human cancellous bone tissues with
      linear simulation. The convergence behavior for human cancellous bone tissue
      using nonlinear constitutive equations needs further investigation. 

PMID- 25070475
TI  - Safety and retention rate of rufinamide in 300 patients: a single pediatric
      epilepsy center experience.
AB  - OBJECTIVE: Reports of studies evaluating rufinamide as an add-on therapy in
      children and adolescents with refractory epilepsy are restricted to a few
      publications. Prospective multicenter studies including children and adults have
      yielded important information about several types of epilepsies and syndromes. We
      evaluated the use of rufinamide in a single pediatric center with a large cohort
      and long-term follow-up period. METHODS: We retrospectively included patients
      taking rufinamide from November 2008 to March 2013. Response was defined by a
      seizure reduction of >=50% compared to baseline. RESULTS: Three hundred patients
      with a median age of 9.1 years (range 0.4-29.6 years) were reviewed. Median
      follow-up was 9 months (range 1-37 months). Epilepsy etiology was classified as
      genetic (23.7%), structural/metabolic (41%), and unknown cause (35.3%). Overall,
      rufinamide treatment led to a median seizure frequency reduction of 59.2% from
      responders to baseline. Seizure reduction was greater in patients with genetic
      etiology compared to structural/metabolic (66.2% vs. 45.5% responders, p =
      0.005). Rufinamide was discontinued in 110 (36.7%) of 300 patients: 63 (21%) due
      to unsatisfactory response, 47 (15.7%) due to side effects, and in 18 (6%) of
      those due to both. Most common adverse effects were sleepiness, vomiting, mood
      changes, nausea, and loss of appetite. Median time to loss of efficacy was 11.6
      months (range 3-28 months). SIGNIFICANCE: Rufinamide provides satisfactory
      seizure reduction as an adjunctive treatment in refractory epilepsy. Results need
      to be interpreted in the setting of data acquisition, including inherent biases
      of retrospective studies. Patients with a known genetic etiology may have better
      responses than patients with structural/metabolic etiology.

PMID- 25070477
TI  - Defensive functioning and psychopathology: a study with the REM-71.
AB  - OBJECTIVES: The aim of the present study is to explore the association between
      defensive functioning (as assessed through the REM-71) and psychiatric symptoms
      in a large sample from the community, and the moderating role of age and gender
      on that association. Furthermore, we explored the concurrent validity of REM-71
      as compared with "caseness" (SCL-90-R). METHODS: The REM-71 was administered
      together with SCL-90-R to a community sample of 1,060 Italian high-school and
      university students (mean age=19.01+/-3.85 years; 66.7% females). RESULTS: Factor
      1 defenses were by far the primary contributors to the predictor synthetic
      variable (i.e. association between defenses and psychopathology). Gender proved
      to moderate the association between immature defenses and symptoms. Using ROC
      analysis, we derived a cut-off score for Factor 1 defenses. CONCLUSIONS: Our
      results support the adoption of the REM-71 as a useful instrument for the
      assessment of defensive array and psychopathological liability in adolescents and
      adults.

PMID- 25070478
TI  - Suicidal behavior in adolescents and adults with bulimia nervosa.
AB  - BACKGROUND: Recent evidence suggests increased risk for mortality in bulimia
      nervosa (BN). However, little is yet known about suicidal behavior in BN. AIMS:
      To examine frequency and correlates of suicidal ideation and attempts in
      adolescents and adults with BN in two population-based samples. METHOD: A total
      of 10,123 adolescents and 2980 adults in two nationally representative surveys of
      mental disorder were queried regarding eating disorder symptoms and suicidal
      ideation and attempts. RESULTS: Less than 1 percent (0.9%) of adolescents and
      1.0% of adults met the criteria for BN. Suicidal ideation was more common among
      adolescents with BN (53.0%) compared with those with binge eating disorder (BED)
      (34.4%), other psychopathology (21.3%) or no psychopathology (3.8%). Similar
      trends emerged for the association between BN and self-reported suicidal plans or
      attempts. Among adults, suicidality was more common in BN than in the no
      psychopathology group, but not significantly different from the anorexia nervosa
      (AN), BED, or other psychopathology subgroups. CONCLUSION: There is a high risk
      of suicidal ideation and behavior among those with BN. These results underscore
      the importance of addressing suicide risk in adolescents and adults with eating
      disorder symptoms.

PMID- 25070479
TI  - An Activin A/BMP2 chimera, AB215, blocks estrogen signaling via induction of ID
      proteins in breast cancer cells.
AB  - BACKGROUND: One in eight women will be affected by breast cancer in her lifetime.
      Approximately 75% of breast cancers express estrogen receptor alpha (ERalpha)
      and/or progesterone receptor and these receptors are markers for tumor dependence
      on estrogen. Anti-estrogenic drugs such as tamoxifen are commonly used to block
      estrogen-mediated signaling in breast cancer. However, many patients either do
      not respond to these therapies (de novo resistance) or develop resistance to them
      following prolonged treatment (acquired resistance). Therefore, it is imperative
      to continue efforts aimed at developing new efficient and safe methods of
      targeting ER activity in breast cancer. METHODS: AB215 is a chimeric ligand
      assembled from sections of Activin A and BMP2. BMP2's and AB215's inhibition of
      breast cancer cells growth was investigated. In vitro luciferase and MTT
      proliferation assays together with western blot, RT_PCR, and mRNA knockdown
      methods were used to determine the mechanism of inhibition of estrogen positive
      breast cancer cells growth by BMP2 and AB215. Additionally in vivo xenograft
      tumor model was used to investigate anticancer properties of AB215. RESULTS: Here
      we report that AB215, a chimeric ligand assembled from sections of Activin A and
      BMP2 with BMP2-like signaling, possesses stronger anti-proliferative effects on
      ERalpha positive breast cancer cells than BMP2. We further show that AB215
      inhibits estrogen signaling by inducing expression of inhibitor of DNA binding
      proteins (IDs). Specifically, we demonstrate that knockdown of ID proteins
      attenuates the anti-estrogen effects of AB215. Remarkably, we find that AB215 is
      more effective than tamoxifen in suppressing tumor growth in a xenograft model.
      CONCLUSION: This study shows that IDs have profound role to inhibit estrogen
      signaling in ERalpha positive breast cancer cells, and that engineered TGF-beta
      ligands may have high therapeutic value.

PMID- 25070480
TI  - Effect of nitric oxide synthase on multiple drug resistance is related to Wnt
      signaling in non-small cell lung cancer.
AB  - Multiple drug resistance (MDR) is considered a major challenge in the clinical
      treatment of non-small cell lung cancer (NSCLC). Both nitric oxide synthase
      (iNOS) and Wnt signaling pathway participate in the regulation of drug
      resistance, but the interaction between them remains unclear. In the present
      study, we detected the activation of Wnt/beta-catenin signaling in iNOS-induced
      drug-resistant lung cancer cells, and compared the effect of canonical and
      noncanonical Wnt pathway on the level of iNOS. Moreover, we investigated the
      expression of Wnt/beta-catenin signaling downstream factors and its main
      inhibitors. The results indicated iNOS-induced drug resistance was possibly
      mediated by glutathione S-transferase-pi (GST-pi) and topoisomerase IIalpha (TOPO
      IIalpha), but not P-glycoprotein (P-gp), and this process was closely associated
      with the activation of canonical Wnt/beta-catenin signaling, but less with
      noncanonical pathways. The mechanism of iNOS promoting Wnt/beta-catenin pathway
      was mainly dependent on the inverse regulation of Dickkopf-1 (DKK-1) and secreted
      frizzled-related protein-1 (SFRP-1). Clarifying the relationship between iNOS and
      Wnt signaling may provide insight into a better understanding of the mechanism of
      drug resistance development in NSCLC. 

PMID- 25070481
TI  - Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced
      by peripheral nerve trauma and the antiretroviral drug stavudine.
AB  - BACKGROUND: Heterogeneity is increasingly recognized in clinical presentation of
      neuropathic pain (NP), but less often recognized in animal models. Neurochemical
      dysregulation in rodent dorsal root ganglia (DRG) is associated with peripheral
      nerve trauma, but poorly studied in non-traumatic NP conditions. METHODS: This
      study aimed to investigate the temporal expressions of activating transcription
      factor-3 (ATF-3), growth-associated protein-43 (GAP-43), neuropeptide Y (NPY) and
      galanin in traumatic and non-traumatic rat models of neuropathies associated with
      NP. Expressions of these markers were examined in the DRG at different time
      points following tibial nerve transection (TNT) injury and antiretroviral drug
      stavudine (d4T) administration using immunohistochemistry. The development of
      sensory gain following these insults was assessed by measuring limb withdrawal to
      a punctate mechanical stimulus. RESULTS: Both TNT-injured and d4T-treated rats
      developed hindpaw mechanical hypersensitivity. Robust expressions of ATF-3, GAP
      43, NPY and galanin in both small- and large-sized L5 DRG neurons were observed
      in the DRG from TNT-injured rats. In contrast, d4T-treated rats did not exhibit
      any significant neurochemical changes in the DRG. CONCLUSIONS: Taken together,
      the results suggest that ATF-3, GAP-43, NPY and galanin are likely indicators of
      nerve trauma-associated processes and not generic markers for NP. These
      experiments also demonstrate distinct expression patterns of neurochemical
      markers in the DRG and emphasize the mechanistic difference between nerve trauma
      and antiretroviral drug-associated NP.

PMID- 25070482
TI  - Effect of excipients on the particle size of precipitated pioglitazone in the
      gastrointestinal tract: impact on bioequivalence.
AB  - This study sought to understand the reasons for the bioinequivalence of a newly
      developed generic product of pioglitazone hydrochloride and to improve its
      formulation so that it is equivalent to that of the reference listed drug (RLD).
      In this clinical study, despite a similar in vitro dissolution profile, the new
      oral product exhibited a lower plasma concentration of pioglitazone compared to
      the RLD. The strong pH-dependency of pioglitazone solubility as a weak base
      indicates that pioglitazone would precipitate in the small intestine after being
      dissolved in the stomach. Thus, in vitro experiments were performed to
      investigate the effect of excipients on the particle size distribution of
      precipitated pioglitazone. Then, the impact of particle size on in vivo
      absorption was discussed. The precipitated pioglitazone from the RLD showed a
      peak for small particles (less than 1 MUm), which was not observed in the
      precipitate from the new product. As an excipient, hydroxypropyl cellulose (HPC)
      influenced the particle size of precipitated pioglitazone, and the amount of HPC
      in the formulation was increased to the same level as that in the RLD. The
      precipitate from this improved product showed approximately the same particle
      size distribution as that of the RLD and successfully demonstrated bioequivalence
      in the clinical study. In conclusion, for drugs with low solubility, this type of
      analysis of the particle size distribution of precipitated drugs, in addition to
      the dissolution test, may help to obtain a better in vitro-in vivo correlation
      for oral absorption and to develop a bioequivalent product.

PMID- 25070483
TI  - Pilot testing of a portion-controlled, commercially available diet on presurgical
      weight loss and metabolic outcomes in patients undergoing bariatric surgery.
AB  - Weight loss prior to bariatric surgery is often recommended, but success with
      weight loss varies. The current study piloted the efficacy of a structured, low
      glycemic portion-controlled diet (PCD) intervention compared to usual dietary
      care (UDC). The study randomized 73 subjects in a 12-week, controlled, randomized
      design. Participants' height, weight, BMI, percent body fat, fasting lipids, and
      glucose were measured at baseline and after 12 weeks. Although both groups had
      significant BMI reductions, there were no differences based upon diet and no
      effect on percent body fat or metabolic outcomes (all p values >0.10). Although
      patients were able to reduce their BMI through dietary intervention, losses were
      minimal. Both groups may have been less adherent or motivated to adopt dietary
      recommendations because of their upcoming bariatric surgery.

PMID- 25070484
TI  - Adjustable gastric banding and sleeve gastrectomy in Bardet-Biedl syndrome.

PMID- 25070485
TI  - Safety and effectiveness of Roux-en-Y gastric bypass in patients between the ages
      of 17 and 19.
AB  - BACKGROUND: Bariatric surgery is becoming more appealing as an option in
      addressing adolescent obesity. Concerns that may be encountered status
      postbariatric surgery include complications and failure to lose weight. The aim
      of our study is to describe safety and effectiveness of laparoscopic Roux-en-Y
      gastric bypass (LRYGB) in patients between the ages of 17 and 19. METHODS: A
      retrospective chart review was completed on LRYGB patients between January 2005
      and May 2012. Fifteen patients less than 20 years of age were included. One
      patient was lost to follow-up, and therefore, 14 patients under the age of 20
      were matched to 14 patients greater than 20 years of age for gender (p > 0.99),
      preoperative body mass index (BMI) (p > 0.96), and follow-up interval (p > 0.80).
      RESULTS: Mean postoperative BMI at last follow-up did not show statistical
      difference between the two (p > 0.74). Mean percentage of excess weight loss
      (%EWL) in patients under the age of 20 was 43.1 +/- 14.6, 70.5 +/- 17.0, 69.8 +/-
      17.3, and 54.8 +/- 8.5 % at postoperative 6, 12, 24, and 36 months, respectively.
      In patients over the age of 20, mean %EWL was 39.9 +/- 12.6, 67.0 +/- 18.6, 60.2
      +/- 11.3, and 56.2 +/- 6.2 %. Both group of patients showed improvement/remission
      of their comorbid conditions. No statistical difference was present between the
      two groups in terms of weight loss and comorbidity resolution. Each group had a
      single patient that required a revision for weight regain. CONCLUSION: LRYGB in
      younger patients almost the age of 20 is both safe and effective when compared to
      matched adults in regard to weight loss, comorbid condition, and complications.

PMID- 25070486
TI  - Antihypertensive effects of gastrointestinal surgery on spontaneously
      hypertensive rats.

PMID- 25070487
TI  - Risk of gastrointestinal perforation in cancer patients treated with aflibercept:
      a systematic review and meta-analysis.
AB  - Gastrointestinal (GI) perforation is a serious adverse event associated with
      aflibercept, a novel vascular endothelial growth factor (VEGF)-targeted agent
      currently approved as second-line treatment for previously treated metastatic
      colorectal cancer, but the incidence and risk of GI perforation associated with
      aflibercept has not been well determined. We thus conducted this meta-analysis to
      investigate the overall incidence and risk of developing GI perforation
      associated with aflibercept. Databases from PubMed, Web of Science, and abstracts
      presented at American Society of Clinical Oncology (ASCO) and European Society of
      Medical Oncology (ESMO) meeting up to January, 2014 were searched to identify
      relevant studies. Eligible studies included prospective phase II and III trials
      evaluating aflibercept in cancer patients with adequate data on GI perforation.
      Statistical analyses were conducted to calculate the summary incidence, odds
      ratio, and 95% confidence intervals (CIs) by using either random effects or fixed
      effect models according to the heterogeneity of included studies. A total of
      4,101 patients with a variety of solid tumors from eight clinical trials were
      included in our analysis. The incidence of GI perforation associated with
      aflibercept was 1.9% (95%CI, 1.0-3.8%), with a mortality of 10.8% (95%CI, 4.1
      25.5%). In addition, patients treated with aflibercept had a significantly
      increased risk of developing all-grade (OR 3.76; 95%CI, 1.94-7.25; p < 0.001) and
      high-grade GI (OR 4.14; 95%CI; 2.12-8.06; p < 0.001) perforation compared with
      patients treated with control medication. No evidence of publication bias was
      observed. The use of aflibercept is associated with a significantly increased
      risk of GI perforation compared to controls.

PMID- 25070488
TI  - SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung
      cancer.
AB  - Lung cancer is one of the leading causes of cancer-related death in developed
      countries. Despite decades of intensive efforts to comate this malignant disease,
      the prognosis of lung cancer remains unfavorable and is especially poor in
      advanced non-small cell lung cancer (NSCLC). Accumulating evidence indicate that
      one of the main causes of the poor outcome in NSCLC treatment is the innate
      resistance of NSCLC patients to anticancer drugs. However, the mechanism
      underling NSCLC development and drug resistance is not fully understood. Here we
      show that the mitochondrial class III NAD(+)-dependent deacetylase SIRT5 is
      overexpressed in human NSCLC and high expression of SIRT5 predicts poor survival.
      SIRT5 knockdown represses lung cancer cell growth and transformation in vitro and
      in vivo. Furthermore, we find that SIRT5 knockdown makes lung cancer cells more
      sensitive to drug (cis-diamminedichloroplatinum [CDDP], 5-fluorouracil [5-FU] or
      bleomycin) treatment in vitro and in vivo. Mechanically, we identify Nrf2, which
      is a core transcription factor for lung cancer growth and drug resistance, as a
      target of SIRT5. SIRT5 mRNA level is positively correlated with the expression of
      Nrf2 in lung cancer tissues and SIRT5 knockdown reduces the expression of Nrf2
      and its downstream drug-resistance genes. Taken together, our findings implicate
      that SIRT5 as a protein responsible for growth and drug resistance in human
      NSCLC, and SIRT5 may serve as a potential prognostic factor and drug target for
      intervention. 

PMID- 25070489
TI  - FTY720 reduces migration and invasion of human glioblastoma cell lines via
      inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway.
AB  - 2-Amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride (FTY720), a synthetic
      compound from Isaria sinclairii, has been proven to possess various biological
      benefits including anti-cancer activity. However, the effects and related
      mechanisms of FTY720 on the migration and invasion of glioblastoma cells are
      still unclear. In the present study, we utilized U251MG and U87MG human
      glioblastoma cell lines to assess the effects of FTY720. We found that FTY720
      significantly inhibited migration and invasion of glioblastoma cells. The anti
      migration and invasion effects of FTY720 were associated with its down-regulation
      of matrix metalloproteinase-2 (MMP-2) and MMP-9 while up-regulation of tissue
      inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Furthermore, FTY720
      modulated the expression of roundabouts 1 (ROBO1), Rho-associated kinase-1
      (ROCK1), and epithelial-to-mesenchymal transition (EMT)-related factors. In
      addition, the phosphatidylinositide 3-kinases/protein kinase B/mammalian target
      of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway participated
      in FTY720-mediated suppression of migration and invasion. Thus, our findings
      demonstrated that FTY720 reduced glioblastoma cells migration and invasion via
      multiple signaling pathways, suggesting that FTY720 is a potential therapeutic
      agent against glioblastoma. 

PMID- 25070491
TI  - Risk factors for bovine respiratory disease in Australian feedlot cattle: use of
      a causal diagram-informed approach to estimate effects of animal mixing and
      movements before feedlot entry.
AB  - A nationwide longitudinal study was conducted to investigate risk factors for
      bovine respiratory disease (BRD) in cattle in Australian feedlots. After
      induction (processing), cattle were placed in feedlot pens (cohorts) and
      monitored for occurrence of BRD over the first 50 days on feed. Data from a
      national cattle movement database were used to derive variables describing mixing
      of animals with cattle from other farms, numbers of animals in groups before
      arrival at the feedlot, exposure of animals to saleyards before arrival at the
      feedlot, and the timing and duration of the animal's move to the vicinity of the
      feedlot. Total and direct effects for each risk factor were estimated using a
      causal diagram-informed process to determine covariates to include in four-level
      Bayesian logistic regression models. Mixing, group size and timing of the
      animal's move to the feedlot were important predictors of BRD. Animals not mixed
      with cattle from other farms prior to 12 days before induction and then exposed
      to a high level of mixing (>=4 groups of animals mixed) had the highest risk of
      developing BRD (OR 3.7) compared to animals mixed at least 4 weeks before
      induction with less than 4 groups forming the cohort. Animals in groups formed at
      least 13 days before induction comprising 100 or more (OR 0.5) or 50-99 (OR 0.8)
      were at reduced risk compared to those in groups of less than 50 cattle. Animals
      moved to the vicinity of the feedlot at least 27 days before induction were at
      reduced risk (OR 0.4) compared to cattle undergoing short-haul transportation
      (<6h) to the feedlot within a day of induction, while those experiencing longer
      transportation durations (6h or more) within a day of induction were at slightly
      increased risk (OR 1.2). Knowledge of these risk factors could potentially be
      used to inform management decisions to reduce the risk of BRD in feedlot cattle. 

PMID- 25070492
TI  - Effect of timing of surgical SSP tendon repair on muscle alterations.
AB  - To investigate the impacts of delayed repairs of a supraspinatus tendon tear on
      the supraspinatus muscle, we used an animal model data from two previously
      published studies in which one supraspinatus (SSP) tendon was detached. In one
      cohort, the rabbits were killed in groups of 10 at 4, 8, and 12 weeks. In the
      other cohort, a repair was done at these time points, 12 rabbits each, and the
      animals killed were 12 weeks later. SSP fossa volume (Muscle belly plus
      extramuscular fat [e-fat] volume), percentage of intramuscular fat (i-fat), and
      muscle tissue volume (muscle belly volume minus i-fat), as well as CT
      determination of e-fat and i-fat of both cohorts, were compared. Fossa volume
      increased (p < 0.05). Muscle belly and muscle tissue volumes did not increase
      after repair (p > 0.05), but early repair prevented further volume losses, a fact
      not seen after 8 and 12 weeks delay of repair. No reversal of e-fat or of i-fat
      occurred, in fact i-fat almost doubled after 4 weeks delay of repair (p < 0.05).
      CT studies confirmed the fat results. We conclude that early repair prevented
      loss of muscle belly and muscle tissue volumes, but that it has no positive
      influence on fat accumulation.

PMID- 25070490
TI  - Novel multiarm polyethylene glycol-dihydroartemisinin conjugates enhancing
      therapeutic efficacy in non-small-cell lung cancer.
AB  - The clinical application of dihydroartemisinin (DHA) has been hampered due to its
      poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug
      conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by
      linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA on
      chemical structure, hydrolysis, solubility, hemolysis, cell cytotoxicity in
      vitro, and efficacy in vivo. The PEG-DHA conjugates have showed moderate drug
      loadings (2.82 ~ 8.14 wt%), significantly good water-solubilities (82- ~ 163-fold
      of DHA), excellent in vitro anticancer activities (at concentrations >=8 MUg/ml,
      showed only 15-20% cell viability) with potency similar to that of native DHA,
      and long blood circulation half-time (5.75- ~ 16.75-fold of DHA). Subsequent
      tumor xenograft assays demonstrated a superior therapeutic effect of PEG-DHA on
      inhibition of tumor growth compared with native DHA. The novel PEG-DHA conjugates
      can not only improve the solubility and efficacy of DHA but also show the
      potential of scale-up production and clinical application.

PMID- 25070493
TI  - New options of antibiotic combination therapy for multidrug-resistant Pseudomonas
      aeruginosa.
AB  - Several antibiotic combinations have demonstrated increased activity against
      multidrug-resistant Pseudomonas aeruginosa (MDRP) in vitro compared with a single
      antibiotic. The aim of this study was to investigate the activity against MDRP of
      some aminoglycosides in combination with monobactam, piperacillin (PIPC), and
      carbapenem. Clinical isolates of MDRP were collected between November 2010 and
      October 2012 from patients in Tokyo Medical University Hospital, Tokyo (1,015
      beds). Our new method was designed to evaluate three concentrations around the
      breakpoint of each drug using the Checkerboard method. The aminoglycosides tested
      were amikacin (AMK), tobramycin (TOB), and arbekacin (ABK). Ciprofloxacin, PIPC,
      and biapenem (BIPM), which have been reported to demonstrate combination effects,
      were also tested. Sixty-six MDRP strains were identified from the 2,417 P.
      aeruginosa strains. Of the 66, 27 tested positive for metallo-beta-lactamase
      (MBL). Aztreonam (AZT) with AMK or ABK was the most effective against MDRP. PIPC
      with AMK or ABK were somewhat effective. AZT with AMK or ABK were more effective
      against MBL-positive strains than MBL-negative strains. However, PIPC with AMK or
      ABK were more effective against MBL-negative strains than MBL-positive strains.
      Combination activities showed differences between MBL-positive and MBL-negative
      strains. 

PMID- 25070495
TI  - The Willingness to Pay for a Quality Adjusted Life Year: A Review of the
      Empirical Literature.
AB  - There has been a rapid increase in the use of cost-effectiveness analysis, with
      quality adjusted life years (QALYs) as an outcome measure, in evaluating both
      medical technologies and public health interventions. Alongside, there is a
      growing literature on the monetary value of a QALY based on estimates of the
      willingness to pay (WTP). This paper conducts a review of the literature on the
      WTP for a QALY. In total, 24 studies containing 383 unique estimates of the WTP
      for a QALY are identified. Trimmed mean and median estimates amount to 74,159 and
      24,226 Euros (2010 price level), respectively. In regression analyses, the
      results indicate that the WTP for a QALY is significantly higher if the QALY gain
      comes from life extension rather than quality of life improvements. The results
      also show that the WTP for a QALY is dependent on the size of the QALY gain
      valued. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25070494
TI  - Epidemic and molecular evolution of human bocavirus in hospitalized children with
      acute respiratory tract infection.
AB  - Human bocavirus (HBoV) is a novel parvovirus, often associated with respiratory
      tract diseases in children. This study explored the epidemiological
      characteristics and molecular evolution of HBoV-1 in southeastern China.
      Nasopharyngeal aspirates were collected from children admitted to hospital with
      acute respiratory tract infections. HBoV-1 was detected using real-time reverse
      transcription polymerase chain reaction and further characterized by complete
      genome sequences analysis. Among the 3,022 recruited children, 386 (12.77%) were
      HBoV-1-positive and 300 (77.72%) had co-detection with other respiratory viruses.
      Seasonal prevalence peaked in summer. HBoV-1 presence was significantly
      associated with asthma attack [odds ratio = 1.74; 95 % confidence interval: 1.30,
      2.31; p < 0.001]. Similar results were obtained when either single detection or
      co-detection of HBoV-1 was considered, demonstrating the minor impact of co
      detection on the clinical characteristics or epidemic pattern. Phylogenetic
      analysis based on the complete genome sequences showed that all the HBoV-1
      sequences clustered together and no branch was formed that was supported by
      bootstrap value >= 750. The overall evolutionary rate of the complete genome of
      HBoV-1 was estimated at 1.08 * 10(-4) nucleotide substitutions per site per year
      (s/s/y) [95% highest probability density: (0.40-1.86) * 10(-4) s/s/y]. Selective
      pressure analysis showed that all the omega-values were less than 1, suggesting
      that HBoV-1 was under negative selective pressure. Site-by-site analysis
      identified the codon site 40 of the VP1 gene under positive selection. In
      conclusion, our study disclosed the epidemiological and genetic dynamics of HBoV
      1 epidemics in southeastern China in the most recent 3 years, the information of
      which might help to further improve our understanding of HBoV-1 infection and
      guide better surveillance and control strategies in the future.

PMID- 25070496
TI  - Cardiac tamponade leading to the diagnosis of eosinophilic granulomatosis with
      polyangiitis (Churg-Strauss syndrome): a case report and review of the
      literature.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called
      Churg-Strauss syndrome, is a necrotizing systemic vasculitis of unknown cause
      accompanied by prominent eosinophilia. Cardiovascular complications, including
      eosinophilic myocarditis, are a major cause of mortality in this disorder. Acute
      pericarditis with slight pericardial effusion is a typical manifestation in EGPA,
      though hemodynamically significant pericardial effusion has been reported in a
      few cases. We report a case that initially presented with isolated cardiac
      tamponade, which was followed by systemic manifestations of EGPA over 3 weeks.
      Including the present case, previous EGPA cases with cardiac tamponade are
      reviewed to delineate its clinical characteristics.

PMID- 25070497
TI  - Donation after cardiac death liver transplantation is associated with increased
      risk of end-stage renal disease.
AB  - Limited organ supply has led to greater use of liver allografts with higher donor
      risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is
      associated with acute kidney injury after liver transplantation; however, less is
      known about the association between donor quality and end-stage renal disease
      (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients
      from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD.
      Model 1 included total DRI; model 2 included components of DRI, including DCD, as
      separate variables. Forty thousand four hundred and sixty-three liver transplant
      recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%)
      received DCD livers. During median follow-up of 3.93 years, ESRD occurred in 2008
      (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD
      risk with higher DRI (DRI >=1.14 and <1.40: HR 1.17, P = 0.06; DRI >=1.40 and
      <1.72: HR 1.29, P = 0.003; DRI >=1.72: HR 1.39, P < 0.001, compared with DRI
      <1.14). Adjusting for DRI components separately, DCD status was most strongly
      associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD
      after liver transplantation, driven in part by DCD status. Donor quality is an
      important predictor of long-term renal outcomes in liver transplant recipients. 

PMID- 25070498
TI  - 'Selective' COX-1 or COX-2 NSAIDs: time to change a misleading measure.
AB  - The ongoing important debate about the relative benefits/risks of COX-1 or COX-2
      NSAIDs is hampered by the use of a measure of 'selectivity' that is inherently
      flawed. An alternative measure provides more meaningful and clinically relevant
      information. 

PMID- 25070499
TI  - Coronary artery surgery results 2013, in Japan.

PMID- 25070500
TI  - Expanded identification and characterization of mammalian circular RNAs.
AB  - BACKGROUND: The recent reports of two circular RNAs (circRNAs) with strong
      potential to act as microRNA (miRNA) sponges suggest that circRNAs might play
      important roles in regulating gene expression. However, the global properties of
      circRNAs are not well understood. RESULTS: We developed a computational pipeline
      to identify circRNAs and quantify their relative abundance from RNA-seq data.
      Applying this pipeline to a large set of non-poly(A)-selected RNA-seq data from
      the ENCODE project, we annotated 7,112 human circRNAs that were estimated to
      comprise at least 10% of the transcripts accumulating from their loci. Most
      circRNAs are expressed in only a few cell types and at low abundance, but they
      are no more cell-type-specific than are mRNAs with similar overall expression
      levels. Although most circRNAs overlap protein-coding sequences, ribosome
      profiling provides no evidence for their translation. We also annotated 635 mouse
      circRNAs, and although 20% of them are orthologous to human circRNAs, the
      sequence conservation of these circRNA orthologs is no higher than that of their
      neighboring linear exons. The previously proposed miR-7 sponge, CDR1as, is one of
      only two circRNAs with more miRNA sites than expected by chance, with the next
      best miRNA-sponge candidate deriving from a gene encoding a primate-specific zinc
      finger protein, ZNF91. CONCLUSIONS: Our results provide a new framework for
      future investigation of this intriguing topological isoform while raising doubts
      regarding a biological function of most circRNAs.

PMID- 25070503
TI  - Donepezil can improve ischemic muscle atrophy by activating angiomyogenic
      properties of satellite cells.
AB  - BACKGROUND: Saving more limbs of patients with peripheral arterial disease (PAD)
      from amputation by accelerating angiogenesis in affected limbs has been
      anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil
      (DPZ), can activate angiomyogenic properties of satellite cells, myogenic
      progenitors, and thus be an additional pharmacological therapy against PAD.
      METHODS AND RESULTS: In a murine hindlimb ischemia model, we investigated the
      angiogenic effects of a clinical dose of DPZ (0.2 mg.kg(-1).day(-1)) and its
      combination with cilostazol, a platelet aggregation inhibitor and a conventional
      therapeutic drug against PAD. The combination therapy most effectively improved
      skin coldness and most effectively upregulated vascular endothelial growth factor
      (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography
      revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super
      restoration in affected hindlimbs. The in vitro study with human aortic
      endothelial cells showed that DPZ or its combination with cilostazol effectively
      upregulated the expression of pAkt, hypoxia inducible factor-1alpha, and VEGF
      protein. Likewise, in primary cultured satellite cells, DPZ, alone or in
      combination, upregulated the expression of VEGF, interleukin-1beta, and
      fibroblast growth factor 2 protein. CONCLUSIONS: The present results suggest that
      a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both
      endothelial and satellite cells. Therefore, DPZ is a potential additional choice
      for conventional drug therapy against PAD.

PMID- 25070504
TI  - Preoperative chronic kidney disease as a strong predictor of postoperative
      infection and mortality after coronary artery bypass grafting.
AB  - BACKGROUND: The aim of this study was to determine the influence of preoperative
      kidney dysfunction (ie, chronic kidney disease (CKD)) on postoperative
      cardiovascular events, infection, acute kidney injury and hospital mortality in
      patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS:
      A multi-institutional retrospective study was performed at 14 hospitals of adult
      patients undergoing isolated CABG from 2007 to 2008 (n=1,522). We classified CKD
      level according to preoperative estimated glomerular filtration rate (eGFR):
      normal, eGFR >90 ml.min(-1).1.73 m(-2); mild, eGFR 60-90 ml.min(-1).1.73 m(-2);
      moderate, eGFR 30-59 ml.min(-1).1.73 m(-2); and severe, eGFR <30 ml.min(-1).1.73
      m(-2), and assessed postoperative outcome. Preoperative CKD distribution was as
      follows: normal, n=121 (8%); mild, n=713 (47%); moderate, n=515 (34%); and
      severe, n=169 (11%). Risk of infection was strongly correlated with CKD level
      (normal, 3.3%; mild, 7.0%; moderate, 8.3%; severe, 17.0%; P<0.01). The risk of in
      hospital death was also strongly correlated with CKD level (normal, 1.7%; mild,
      1.0%; moderate, 1.6%; severe, 5.9%; P<0.01). On multivariate logistic regression
      analysis, CKD level was identified as a significant risk factor for postoperative
      infection, acute kidney injury, and in-hospital death. CONCLUSIONS: Advanced
      preoperative CKD is a strong predictor of postoperative infection, acute kidney
      injury and in-hospital death after CABG.

PMID- 25070505
TI  - Irrigation solutions in head and neck cancer surgery: a preclinical efficacy
      study.
AB  - INTRODUCTION: It is common practice to irrigate the operative site following
      tumor resection during major head and neck surgery. A variety of irrigation
      solutions are used, but there are few data on their relative efficacies in this
      context. METHODS: The effect of different irrigation solutions on cell survival
      was assessed by clonogenic survival assay in 5 head and neck squamous cell
      carcinoma cell lines at different time points. RESULTS: Saline had no effect on
      cell survival in any of the cell lines tested. Hydrogen peroxide, povidone
      iodine, and a hydrogen peroxide/povidone-iodine mix caused complete cell death in
      all cell lines. Irrigation with distilled water caused a significant reduction in
      cell survival in 3 cell lines. Duration of exposure showed no effect on cell
      survival. CONCLUSION: These data suggest a significant difference in the
      cytocidal effect of commonly used irrigation solutions on head and neck cancer
      cells in an in vitro model.

PMID- 25070506
TI  - Atomically dispersed rhodium on a support: the influence of a metal precursor and
      a support.
AB  - The influence of the support type and the metal precursor on the dispersion of
      rhodium after calcination and reduction was determined. The combination of
      electron microscopy and X-ray absorption analysis allowed the quantification of
      the amount of atomically dispersed rhodium in the samples. Higher amounts of
      atomically dispersed rhodium atoms are obtained when metal impregnation is
      performed with a rhodium acetate precursor in comparison to a rhodium chloride
      precursor over supports of the same composition. The stability of rhodium is
      improved with the addition of promoters; the co-presence of samaria and ceria in
      the support and metal impregnation with a rhodium acetate precursor leads to the
      highest amount of atomically dispersed rhodium remaining after reductive
      treatment at 773 K. 

PMID- 25070507
TI  - Emergency departments: a victim of our own success?

PMID- 25070508
TI  - Resilience in patients and spouses faced with malignant melanoma. A qualitative
      longitudinal study.
AB  - Life-threatening diseases like malignant tumours are associated with considerable
      existential distress. Little is known about the factors that promote resilience
      within these individuals. This longitudinal qualitative partner study aimed to
      analyse resilience as per Antonovsky's sense of coherence. Eight patients with
      malignant melanoma and their partners were interviewed. They were asked about
      their coping strategies, attitudes towards the meaning of life and their cancer,
      and comprehension of what is happening to them. The questions were asked shortly
      after their diagnosis was made and 6 months later. All interviews were audio
      taped and later transcribed and analysed according to the method of qualitative
      content analysis described by P. Mayring. At baseline, the majority of statements
      made (261; patients = 141/spouses = 120) related to coping/manageability of
      disease, with only 26 statements (patients = 15/spouses = 11) related to meaning
      and 127 (patients = 64/spouses = 63) to comprehension. There were no significant
      differences between the responses of patients and their partners and no
      significant changes in the number of statements during the 6-month interview. The
      most significant theme that emerged was manageability of disease, with
      distraction the most commonly utilised coping skill. The comprehension and
      meaning themes were far less prevalent. Hence, support should focus on disease
      and situational manageability. 

PMID- 25070510
TI  - Long-term asymmetrical acceleration of protein evolution after gene duplication.
AB  - Rapid divergence of gene copies after duplication is thought to determine the
      fate of the copies and evolution of novel protein functions. However, data on how
      long the gene copies continue to experience an elevated rate of evolution remain
      scarce. Standard theory of gene duplications based on some level of genetic
      redundancy of gene copies predicts that the period of accelerated evolution must
      end relatively quickly. Using a maximum-likelihood approach we estimate
      preduplication, initial postduplication, and recent postduplication rates of
      evolution that occurred in the mammalian lineage. We find that both gene copies
      experience a similar in magnitude acceleration in their rate of evolution. The
      copy located in the original genomic position typically returns to the
      preduplication rates of evolution in a short period of time. The burst of faster
      evolution of the copy that is located in a new genomic position typically lasts
      longer. Furthermore, the fast-evolving copies on average continue to evolve
      faster than the preduplication rates far longer than predicted by standard theory
      of gene duplications. We hypothesize that the prolonged elevated rates of
      evolution are determined by functional properties that were acquired during, or
      soon after, the gene duplication event. 

PMID- 25070509
TI  - Genome evolution and plasticity of Serratia marcescens, an important multidrug
      resistant nosocomial pathogen.
AB  - Serratia marcescens is an important nosocomial pathogen that can cause an array
      of infections, most notably of the urinary tract and bloodstream. Naturally, it
      is found in many environmental niches, and is capable of infecting plants and
      animals. The emergence and spread of multidrug-resistant strains producing
      extended-spectrum or metallo beta-lactamases now pose a threat to public health
      worldwide. Here we report the complete genome sequences of two carefully selected
      S. marcescens strains, a multidrug-resistant clinical isolate (strain SM39) and
      an insect isolate (strain Db11). Our comparative analyses reveal the core genome
      of S. marcescens and define the potential metabolic capacity, virulence, and
      multidrug resistance of this species. We show a remarkable intraspecies genetic
      diversity, both at the sequence level and with regards genome flexibility, which
      may reflect the diversity of niches inhabited by members of this species. A
      broader analysis with other Serratia species identifies a set of approximately
      3,000 genes that characterize the genus. Within this apparent genetic diversity,
      we identified many genes implicated in the high virulence potential and
      antibiotic resistance of SM39, including the metallo beta-lactamase and multiple
      other drug resistance determinants carried on plasmid pSMC1. We further show that
      pSMC1 is most closely related to plasmids circulating in Pseudomonas species. Our
      data will provide a valuable basis for future studies on S. marcescens and new
      insights into the genetic mechanisms that underlie the emergence of pathogens
      highly resistant to multiple antimicrobial agents. 

PMID- 25070511
TI  - Lesion mapping of social problem solving.
AB  - Accumulating neuroscience evidence indicates that human intelligence is supported
      by a distributed network of frontal and parietal regions that enable complex,
      goal-directed behaviour. However, the contributions of this network to social
      aspects of intellectual function remain to be well characterized. Here, we report
      a human lesion study (n = 144) that investigates the neural bases of social
      problem solving (measured by the Everyday Problem Solving Inventory) and examine
      the degree to which individual differences in performance are predicted by a
      broad spectrum of psychological variables, including psychometric intelligence
      (measured by the Wechsler Adult Intelligence Scale), emotional intelligence
      (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and
      personality traits (measured by the Neuroticism-Extraversion-Openness Personality
      Inventory). Scores for each variable were obtained, followed by voxel-based
      lesion-symptom mapping. Stepwise regression analyses revealed that working
      memory, processing speed, and emotional intelligence predict individual
      differences in everyday problem solving. A targeted analysis of specific everyday
      problem solving domains (involving friends, home management, consumerism, work,
      information management, and family) revealed psychological variables that
      selectively contribute to each. Lesion mapping results indicated that social
      problem solving, psychometric intelligence, and emotional intelligence are
      supported by a shared network of frontal, temporal, and parietal regions,
      including white matter association tracts that bind these areas into a
      coordinated system. The results support an integrative framework for
      understanding social intelligence and make specific recommendations for the
      application of the Everyday Problem Solving Inventory to the study of social
      problem solving in health and disease.

PMID- 25070512
TI  - Response inhibition and serotonin in autism: a functional MRI study using acute
      tryptophan depletion.
AB  - It has been suggested that the restricted, stereotyped and repetitive behaviours
      typically found in autism are underpinned by deficits of inhibitory control. The
      biological basis of this is unknown but may include differences in the modulatory
      role of neurotransmitters, such as serotonin, which are implicated in the
      condition. However, this has never been tested directly. We therefore assessed
      the modifying role of serotonin on inhibitory brain function during a Go/No-Go
      task in 14 adults with autism and normal intelligence and 14 control subjects
      that did not differ in gender, age and intelligence. We undertook a double-blind,
      placebo-controlled, crossover trial of acute tryptophan depletion using
      functional magnetic resonance imaging. Following sham, adults with autism
      relative to controls had reduced activation in key inhibitory regions of inferior
      frontal cortex and thalamus, but increased activation of caudate and cerebellum.
      However, brain activation was modulated in opposite ways by depletion in each
      group. Within autistic individuals depletion upregulated fronto-thalamic
      activations and downregulated striato-cerebellar activations toward control sham
      levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite
      pattern occurred in controls. Moreover, the severity of autism was related to the
      degree of differential modulation by depletion within frontal, striatal and
      thalamic regions. Our findings demonstrate that individuals with autism have
      abnormal inhibitory networks, and that serotonin has a differential, opposite,
      effect on them in adults with and without autism. Together these factors may
      partially explain the severity of autistic behaviours and/or provide a novel
      (tractable) treatment target. 

PMID- 25070513
TI  - TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and
      severe cognitive impairment.
AB  - Autosomal dominant cerebellar ataxia corresponds to a clinically and genetically
      heterogeneous group of neurodegenerative disorders that primarily affect the
      cerebellum. Here, we report the identification of the causative gene in
      spinocerebellar ataxia 21, an autosomal-dominant disorder previously mapped to
      chromosome 7p21.3-p15.1. This ataxia was firstly characterized in a large French
      family with slowly progressive cerebellar ataxia, accompanied by severe cognitive
      impairment and mental retardation in two young children. Following the
      recruitment of 12 additional young family members, linkage analysis enabled us to
      definitively map the disease locus to chromosome 1p36.33-p36.32. The causative
      mutation, (c.509C>T/p.P170L) in the transmembrane protein gene TMEM240, was
      identified by whole exome sequencing and then was confirmed by Sanger sequencing
      and co-segregation analyses. Index cases from 368 French families with autosomal
      dominant cerebellar ataxia were also screened for mutations. In seven cases, we
      identified a range of missense mutations (c.509C>T/p.P170L, c.239C>T/p.T80M,
      c.346C>T/p.R116C, c.445G>A/p.E149K, c.511C>T/p.R171W), and a stop mutation
      (c.489C>G/p.Y163*) in the same gene. TMEM240 is a small, strongly conserved
      transmembrane protein of unknown function present in cerebellum and brain.
      Spinocerebellar ataxia 21 may be a particular early-onset disease associated with
      severe cognitive impairment.

PMID- 25070514
TI  - Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy,
      vestibular areflexia 'CANVAS' syndrome.
AB  - Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a
      recently recognized neurodegenerative ganglionopathy. Prompted by the presence of
      symptomatic postural hypotension in two patients with CANVAS, we hypothesized
      that autonomic dysfunction may be an associated feature of the syndrome. We
      assessed symptoms of autonomic dysfunction and performed autonomic nervous system
      testing among 26 patients from New Zealand. After excluding three patients with
      diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at
      least one autonomic symptom and 91% had more than two symptoms. We also found a
      higher rate of downbeat nystagmus (65%) than previously described in CANVAS. We
      confirmed that sensory findings on nerve conduction tests were consistent with a
      sensory ganglionopathy and describe two patients with loss of trigeminal
      sensation consistent with previous pathological descriptions of trigeminal
      sensory ganglionopathy. Our results suggest that autonomic dysfunction is a major
      feature of CANVAS. This has implications for the management of patients with
      CANVAS as the autonomic symptoms may be amenable to treatment. The findings also
      provide an important differential diagnosis from multiple system atrophy for
      patients who present with ataxia and autonomic failure.

PMID- 25070515
TI  - A chemoenzymatic approach to protein immobilization onto crystalline cellulose
      nanoscaffolds.
AB  - The immobilization of bioactive molecules onto nanocellulose leads to constructs
      that combine the properties of the grafted compounds with the biocompatibility
      and low cytotoxicity of cellulose carriers and the advantages given by their
      nanometer dimensions. However, the methods commonly used for protein grafting
      suffer from lack of selectivity, long reaction times, nonphysiological pH ranges
      and solvents, and the necessity to develop a tailor-made reaction strategy for
      each individual case. To overcome these restrictions, a generic two-step
      procedure was developed that takes advantage of the highly efficient oxime
      ligation combined with enzyme-mediated protein coupling onto the surface of
      peptide-modified crystalline nanocellulose. The described method is based on
      efficient and orthogonal transformations, requires no organic solvents, and takes
      place under physiological conditions. Being site-directed and regiospecific, it
      could be applied to a vast number of functional proteins. 

PMID- 25070516
TI  - Beneficial effects of melatonin on bovine oocytes maturation: a mechanistic
      approach.
AB  - This study was performed to investigate the effect of melatonin on bovine oocyte
      maturation and subsequent embryonic development in vitro. The endogenous
      melatonin concentration in bovine follicular fluid is approximately 10(-11) M. To
      examine the potential beneficial effects of melatonin on bovine oocyte maturation
      in vitro, germinal vesicle (GV) oocytes were incubated with different
      concentrations of melatonin (10(-11), 10(-9), 10(-7), 10(-5), 10(-3) M).
      Melatonin supplementation at suitable concentrations significantly promoted
      oocyte maturation. The development of embryos and the mean cell number/blastocyst
      produced after in vitro fertilization were remarkably improved. The most
      effective melatonin concentrations obtained from the studies ranged from 10(-9)
      to 10(-7) M. The expression of melatonin receptor MT1 and MT2 genes was
      identified in cumulus cells, granulosa cells, and oocytes using reverse
      transcription PCR, immunofluorescence, and Western blot. The mechanistic studies
      show that the beneficial effects of melatonin on bovine oocyte maturation are
      mediated via melatonin membrane receptors as the melatonin receptor agonist
      (IIK7) promotes this effect while the melatonin receptor antagonist (luzindole)
      blocks this action. Mechanistic explorations revealed that melatonin
      supplementation during bovine oocyte maturation significantly up-regulated the
      expressions of oocyte maturation-associated genes (GDF9, MARF1, and DNMT1a) and
      cumulus cells expansion-related gene (PTX3, HAS1/2) and that LHR1/2, EGFR are
      involved in signal transduction and epigenetic reprogramming. The results
      obtained from the studies provide new information regarding the mechanisms by
      which melatonin promotes bovine oocyte maturation in vitro and provide an
      important reference for in vitro embryo production of bovine and the human
      assisted reproductive technology.

PMID- 25070517
TI  - [Central blood pressure and vascular damage].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to assess the relationship
      between central blood pressure and vascular damage. PATIENTS AND METHODS: This
      cross-sectional study involved 393 never treated hypertensive patients (166
      women). Clinical blood pressure (BP), 24h blood pressure (BP24h) and central
      blood pressure (CBP) were measured. Vascular organ damage (VOD) was assessed by
      calculating the albumin/creatinine ratio (ACR), wave pulse pressure velocity and
      echocardiographic left ventricular mass index (LVMI). RESULTS: Patients with VOD
      had higher values of BP, BP24h, and CBP than patients without ACR. When comparing
      several systolic BP, systolic BP24h had a higher linear correlation with CBP (Z
      Steiger test: 2.26; P=.02) and LVMI (Z Steiger test: 3.23; P=.01) than PAC. In a
      multiple regression analysis corrected by age, sex and metabolic syndrome, all
      pressures were related with VOD but systolic BP24h showed the highest
      correlation. In a logistic regression analysis, having the highest tercile of
      systolic BP24h was the stronger predictor of VOD (multivariate odds ratio: 3.4;
      CI 95%: 2.5-5.5, P=.001). CONCLUSIONS: CBP does not have more correlation with
      VOD than other measurements of peripheral BP. Systolic BP24h is the BP
      measurement that best predicts VOD.

PMID- 25070518
TI  - [Treatment of pulmonary arterial hypertension].
AB  - Treatment of pulmonary arterial hypertension has achieved significant progress
      over the past 20 years. Currently, 3 groups of drugs have proven useful for the
      treatment of this disease: endothelin receptor antagonist, phosphodiesterase
      inhibitors and prostacyclin and its analogues. It is recommended to initiate
      treatment with one of these drugs, the choice depending on the initial severity
      of patient disease and the preferences of the treating physician. When the
      patient does not have a satisfactory response, new drugs acting at a different
      pathway are most commonly added. At this time, considering referral for lung
      transplantation could be an alternative. Most experts recommend grouping maximum
      experience in what is known as expert centers. Treatment has led to better
      survival in these patients, but there is still a long way to cure this life
      threatening disease. 

PMID- 25070519
TI  - [Littoral cell angioma. An uncommon cause of constitutional syndrome].

PMID- 25070520
TI  - [Diagnostic clues for giant cell arteritis: beyond headache and ischemic optic
      neuritis].

PMID- 25070522
TI  - Psychosomatic consideration to the burning mouth syndrome.

PMID- 25070521
TI  - [Aerodigestive fistula formation in antiangiogenic tyrosine kinase inhibitor
      therapy].

PMID- 25070524
TI  - Inkjet printed bilayer light-emitting electrochemical cells for display and
      lighting applications.
AB  - A new bilayer light-emitting electrochemical cell (LEC) device, which allows well
      defined patterned light emission through an easily adjustable, mask-free, and
      additive fabrication process, is reported. The bilayer stack comprises an inkjet
      printed lattice of micrometer-sized electrolyte droplets, in a "filled" or
      "patterned" lattice configuration. On top of this, a thin layer of light-emitting
      compound is deposited from solution. The light emission is demonstrated to
      originate from regions proximate to the interfaces between the inkjetted
      electrolyte, the light-emitting compound, and one electrode, where bipolar
      electron/hole injection and electrochemical doping are facilitated by ion motion.
      By employing KCF3 SO3 in poly(ethylene glycol) as the electrolyte, Super Yellow
      as the light-emitting compound, and two air-stabile electrodes, it is possible to
      realize filled lattice devices that feature uniform yellow-green light emission
      to the naked eye, and patterned lattice devices that deliver well-defined and
      high-contrast static messages with a pixel density of 170 PPI. 

PMID- 25070523
TI  - Aging and alcohol interact to alter hepatic DNA hydroxymethylation.
AB  - BACKGROUND: Aging and chronic alcohol consumption are both modifiers of DNA
      methylation, but it is not yet known whether chronic alcohol consumption also
      alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by
      oxidation of methylcytosine. Furthermore, it has not been tested whether aging
      and alcohol interact to modify this epigenetic phenomenon, thereby having an
      independent effect on gene expression. METHODS: Old (18 months) and young (4
      months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with
      alcohol (18% of energy) or an isocaloric Lieber-DeCarli control diet for 5 weeks.
      Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA
      using a new liquid chromatography-tandem mass spectrometry method. Hepatic mRNA
      expression of the Tet enzymes were measured via quantitative real-time polymerase
      chain reaction. RESULTS: In young mice, mild chronic alcohol exposure
      significantly reduced global DNA hydroxymethylation compared with control mice
      (0.22 +/- 0.01 vs. 0.29 +/- 0.06%, p = 0.004). Alcohol did not significantly
      alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet
      showed decreased global DNA hydroxymethylation compared with young mice fed the
      control diet (0.24 +/- 0.02 vs. 0.29 +/- 0.06%, p = 0.04). This model suggests an
      interaction between aging and alcohol in determining DNA hydroxymethylation
      (pinteraction  = 0.009). Expression of Tet2 and Tet3 was decreased in the old
      mice relative to the young (p < 0.005). CONCLUSIONS: The observation that alcohol
      alters DNA hydroxymethylation indicates a new epigenetic effect of alcohol. This
      is the first study demonstrating the interactive effects of chronic alcohol
      consumption and aging on DNA hydroxymethylation.

PMID- 25070525
TI  - Treatment of recalcitrant warts with intralesional measles, mumps, and rubella
      vaccine: a promising approach.
AB  - BACKGROUND: Recalcitrant warts represent a frustrating challenge for both
      patients and physicians. Although many destructive and immunotherapeutic
      modalities are available for the treatment of warts, an ideal, universally
      effective approach has not been explored to date. Recently, intralesional antigen
      immunotherapy has shown promising efficacy in the treatment of warts. The aim of
      the study was to evaluate the efficacy and safety of intralesional measles,
      mumps, and rubella (MMR) vaccine in the treatment of recalcitrant warts. METHODS:
      The study included 70 adult patients with multiple recalcitrant extragenital
      warts of different sizes and durations, with or without distant warts. They were
      directly injected, without a pre-sensitization skin test, with 0.3 intralesional
      MMR vaccine into the largest wart at 2-week intervals until complete clearance or
      for a maximum of five treatments. Follow-up was made every month for six months
      to detect any recurrence. RESULTS: Sixty-five patients, 35 men and 30 women,
      completed the study, and five patients discontinued for various reasons. Complete
      clearance of the lesions was observed in 41 patients (63%), partial response in
      15 patients (23%), and no response in nine patients (14%). Complete response was
      demonstrated in 74.5% of those presenting with distant warts. Side effects were
      mild and insignificant in the form of pain during injection, itching, erythema,
      and edema at the site of injection and flu-like symptoms. Recurrence was detected
      in two patients only. CONCLUSIONS: Intralesional immunotherapy by MMR vaccine is
      a promising, effective, and safe treatment modality for recalcitrant warts.

PMID- 25070526
TI  - Unravelling the correlated electronic and optical properties of BaTaO2N with
      perovskite-type structure as a potential candidate for solar energy conversion.
AB  - We report on the first principles calculation of the electronic, structural and
      optical properties of BaTaO2N, using density functional theory (DFT) and finite
      difference time domain (FDTD) methods. Band structure calculations were performed
      to calculate the direct and indirect bandgaps of the material. Density of states
      and Mulliken charge analysis as well as the electronic contour maps were
      established to determine the type of bonding and hybridization between the
      various electronic states. The dielectric constant, reflectivity, absorption,
      optical conductivity and energy-loss function were also calculated. Moreover,
      FDTD was used to investigate the optical properties of a larger and more reliable
      structure of BaTaO2N powder in good agreement with the reported experimental
      parameters. The calculated electronic, structural and optical properties showed
      the potential of BaTaO2N for solar energy conversion and optoelectronic
      applications. 

PMID- 25070527
TI  - Evaluation of corneal collagen cross-linking as an additional therapy in mycotic
      keratitis.
AB  - BACKGROUND: To report the treatment outcomes of mycotic keratitis with collagen
      cross-linking. DESIGN: Retrospective study. PARTICIPANTS: Patients with smear
      positive moderate mycotic keratitis. METHODS: A retrospective case-file analysis
      was performed to identify cases of moderate mycotic keratitis treated with and
      without additional collagen cross-linking, in addition to intensive topical
      antifungal therapy. Patients in which collagen cross-linking was performed on the
      day of presentation (group 1) were compared with patients who received medical
      treatment alone in the form of 5% natamycin eye drops (group 2). MAIN OUTCOME
      MEASURES: The primary outcome measure was the time taken for resolution of
      infection. RESULTS: Overall, 41 cases were included for analysis (group 1, 20
      cases; group 2, 21 cases). Mean age of the patients was comparable in both groups
      (46.5 +/- 17.01 vs. 41.2 +/- 20.7 years; P = 0.36). Average infiltrate size was
      16.35 +/- 6.8 mm(2) in group 1 and 17.09 +/- 7.4 mm(2) in group 2 (P = 0.83).
      Overall, Aspergillus was the most commonly isolated organism (n = 4 group 1; n =
      6 group 2). Resolution of infection was observed in 18 cases (90%) in group 1 and
      18 (85.71%) cases in group 2. The average healing time was 30.85 +/- 26.6 days in
      group 1, while it was 31.28 +/- 19.97 days in group 2 (P = 0.94). Final best
      corrected visual acuity in group 1 was 1.13 +/- 0.55 and 1.25 +/- 0.46 in group 2
      (P = 0.46). A tectonic keratoplasty was performed in two cases in group 1 and
      three cases in group 2 (P = 1.00). CONCLUSIONS: In our study, additional collagen
      cross-linking treatment did not have any advantage over medical management in
      cases with moderate mycotic keratitis.

PMID- 25070528
TI  - Preventive and therapeutic effects of Zataria multiflora methanolic extract on
      hydatid cyst: an in vivo study.
AB  - The phenolic compounds of Zataria multiflora extract, were identified by HPLC
      analysis. Gallic acid, catechin, caffeic acid, and quercetin were found to be the
      major phenolic compounds. Eighty healthy laboratory Balb/C mice were infected
      intraperitoneally by injection of 1500 viable protoscoleces and were divided into
      prevention (40 mice) and therapeutic (40 mice) groups. To prove the preventive
      effect of Z. multiflora extract on development of hydatid cyst, the 40 infected
      animals were allocated into three treatment groups including Z. multiflora (4 g/l
      in drinking water for 8 months), albendazole (150 mg/kg BW/day for 10 days) and
      untreated (control) group. To estimate the therapeutic effect of Z. multiflora
      extract on the hydatid cyst, after 8 months of infection, the infected mice were
      allocated into three experimental treatment groups including Z. multiflora (8 g/l
      in drinking water for 30 days), albendazole (300 mg/kg BW/day for 20 days) and
      untreated (control) group. At the end of the treatment period, all mice were
      euthanized and necropsied, the hydatid cysts were carefully removed, weighed and
      their size were recorded. Weight and size of the hydatid cysts significantly
      decreased (p<0.05) upon the treatment with Z. multiflora extract in both
      prevention and therapeutic groups. The germinal layer of the hydatid cysts
      recovered from the treated mice, either from the prevention or therapeutic group,
      were completely damaged at ultrastructural level by scanning electron microscopy.

PMID- 25070529
TI  - Feasibility and accuracy of point-of-care pocket-size ultrasonography performed
      by medical students.
AB  - BACKGROUND: Point-of-care ultrasound performed by clinicians is a useful
      supplement in the treatment and assessment of patients. We aimed to investigate
      whether medical students with minimal training were able to successfully acquire
      and interpret ultrasound images using a pocket-size imaging device (PSID) as a
      supplement to their clinical practice. METHODS: Thirty 5th year (of six) medical
      students volunteered to participate. They were each given a personal PSID device
      to use as a supplement to their physical examination during their allocated
      hospital terms. Prior to clinical placement the students were given three
      evenings of hands-on training with PSID by a board certified
      radiologist/cardiologist, including three short lectures (<20 min). The students
      were shown basic ultrasound techniques and taught to assess for basic, clinically
      relevant pathology. They were specifically instructed to assess for the presence
      or absence of reduced left ventricular function (assessed as mitral annular
      excursion < 10 mm), pericardial effusion, pleural effusion, lung comets,
      hydronephrosis, bladder distension, gallstones, abdominal free-fluid,
      cholecystitis, and estimate the diameter of abdominal aorta and inferior vena
      cava. RESULTS: A total of 211 patients were examined creating 1151 ultrasound
      recordings. Acceptable organ presentation was 73.8% (95% CI 63.1-82.6) for
      cardiovascular and 88.4% (95% CI: 80.6-93.6) for radiological structures.
      Diagnostic accuracy was 93.5% (95% CI: 89.0-96.2) and 93.2% (95% CI: 87.4-96.5)
      respectively. CONCLUSION: Medical students with minimal training were able to use
      PSID as a supplement to standard physical examination and successfully acquire
      acceptable relevant organ recordings for presentation and correctly interpret
      these with great accuracy.

PMID- 25070534
TI  - Endogenous small-noncoding RNAs and their roles in chilling response and stress
      acclimation in Cassava.
AB  - BACKGROUND: Small noncoding RNA (sncRNA), including microRNAs (miRNAs) and
      endogenous small-interfering RNAs (endo-siRNAs) are key gene regulators in
      eukaryotes, playing critical roles in plant development and stress tolerance.
      Trans-acting siRNAs (ta-siRNAs), which are secondary siRNAs triggered by miRNAs,
      and siRNAs from natural antisense transcripts (nat-siRNAs) are two well-studied
      classes of endo-siRNAs. RESULTS: In order to understand sncRNAs' roles in plant
      chilling response and stress acclimation, we performed a comprehensive study of
      miRNAs and endo-siRNAs in Cassava (Manihot esculenta), a major source of food for
      the world populations in tropical regions. Combining Next-Generation sequencing
      and computational and experimental analyses, we profiled and characterized sncRNA
      species and mRNA genes from the plants that experienced severe and moderate
      chilling stresses, that underwent further severe chilling stress after chilling
      acclimation at moderate stress, and that grew under the normal condition. We also
      included castor bean (Ricinus communis) in our study to understand conservation
      of sncRNAs. In addition to known miRNAs, we identified 32 (22 and 10) novel
      miRNAs as well as 47 (26 and 21) putative secondary siRNA-yielding and 8 (7 and
      1) nat-siRNA-yielding candidate loci in Cassava and castor bean, respectively.
      Among the expressed sncRNAs, 114 miRNAs, 12 ta-siRNAs and 2 nat-siRNAs showed
      significant expression changes under chilling stresses. CONCLUSION: Systematic
      and computational analysis of microRNAome and experimental validation
      collectively showed that miRNAs, ta-siRNAs, and possibly nat-siRNAs play
      important roles in chilling response and chilling acclimation in Cassava by
      regulating stress-related pathways, e.g. Auxin signal transduction. The
      conservation of these sncRNA might shed lights on the role of sncRNA-mediated
      pathways affected by chilling stress and stress acclimation in Euphorbiaceous
      plants.

PMID- 25070535
TI  - Determinants of telomere attrition over 1 year in healthy older women: stress and
      health behaviors matter.
AB  - Telomere length, a reliable predictor of disease pathogenesis, can be affected by
      genetics, chronic stress and health behaviors. Cross-sectionally, highly stressed
      postmenopausal women have shorter telomeres, but only if they are inactive.
      However, no studies have prospectively examined telomere length change over a
      short period, and if rate of attrition is affected by naturalistic factors such
      as stress and engagement in healthy behaviors, including diet, exercise, and
      sleep. Here we followed healthy women over 1 year to test if major stressors that
      occurred over the year predicted telomere shortening, and whether engaging in
      healthy behaviors during this period mitigates this effect. In 239
      postmenopausal, non-smoking, disease-free women, accumulation of major life
      stressors across a 1-year period predicted telomere attrition over the same
      period-for every major life stressor that occurred during the year, there was a
      significantly greater decline in telomere length over the year of 35 bp (P<0.05).
      Yet, these effects were moderated by health behaviors (interaction B=0.19,
      P=0.04). Women who maintained relatively higher levels of health behaviors (1
      s.d. above the mean) appeared to be protected when exposed to stress. This
      finding has implications for understanding malleability of telomere length, as
      well as expectations for possible intervention effects. This is the first study
      to identify predictors of telomere length change over the short period of a year.

PMID- 25070536
TI  - In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural
      stem progenitor cells.
AB  - Human mutations in PQBP1, a molecule involved in transcription and splicing,
      result in a reduced but architecturally normal brain. Examination of a
      conditional Pqbp1-knockout (cKO) mouse with microcephaly failed to reveal either
      abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural
      stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we
      observed an increase in the length of the cell cycle, particularly for the M
      phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem
      cell pool in vivo was decreased at E10 and remained at a low level during
      neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived
      from the cKO mouse revealed significant changes in gene groups that control the M
      phase, including anaphase-promoting complex genes, via aberrant transcription and
      RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes,
      recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by
      Pqbp1-cKO. These data reveal a mechanism of brain size control based on the
      simple reduction of the NSPC pool by cell cycle time elongation. Finally, we
      demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal
      injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with
      preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO
      mice, opening a new strategy for treating this intractable developmental
      disorder. 

PMID- 25070537
TI  - Dietary patterns and cognitive decline in an Australian study of ageing.
AB  - The aim of this paper was to investigate the association of three well-recognised
      dietary patterns with cognitive change over a 3-year period. Five hundred and
      twenty-seven healthy participants from the Australian Imaging, Biomarkers and
      Lifestyle study of ageing completed the Cancer Council of Victoria food frequency
      questionnaire at baseline and underwent a comprehensive neuropsychological
      assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological
      test scores were used to construct composite scores for six cognitive domains and
      a global cognitive score. Based on self-reported consumption, scores for three
      dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western
      diet and (3) prudent diet were generated for each individual. Linear mixed model
      analyses were conducted to examine the relationship between diet scores and
      cognitive change in each cognitive domain and for the global score. Higher
      baseline adherence to the AusMeDi was associated with better performance in the
      executive function cognitive domain after 36 months in apolipoprotein E (APOE) E4
      allele carriers (P<0.01). Higher baseline western diet adherence was associated
      with greater cognitive decline after 36 months in the visuospatial cognitive
      domain in APOE E4 allele non-carriers (P<0.01). All other results were not
      significant. Our findings in this well-characterised Australian cohort indicate
      that adherence to a healthy diet is important to reduce risk for cognitive
      decline, with the converse being true for the western diet. Executive function
      and visuospatial functioning appear to be particularly susceptible to the
      influence of diet. 

PMID- 25070538
TI  - Oxytocin's neurochemical effects in the medial prefrontal cortex underlie
      recovery of task-specific brain activity in autism: a randomized controlled
      trial.
AB  - The neuropeptide oxytocin may be an effective therapeutic strategy for the
      currently untreatable social and communication deficits associated with autism.
      Our recent paper reported that oxytocin mitigated autistic behavioral deficits
      through the restoration of activity in the ventromedial prefrontal cortex
      (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during
      a socio-communication task. However, it is unknown whether oxytocin exhibited
      effects at the neuronal level, which was outside of the specific task examined.
      In the same randomized, double-blind, placebo-controlled, within-subject cross
      over clinical trial in which a single dose of intranasal oxytocin (24 IU) was
      administered to 40 men with high-functioning autism spectrum disorder
      (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker
      for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance
      spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin
      and placebo sessions were associated with oxytocin-induced fMRI signal changes in
      the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted
      by the NAA differences between the oxytocin and placebo sessions (P=0.002), an
      effect that remained after controlling for variability in the time between the
      fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and
      placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in
      the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC,
      which consequently led to improvements in the socio-communication difficulties
      associated with autism. The present study suggests that the beneficial effects of
      oxytocin are not limited to the autistic behavior elicited by our psychological
      task, but may generalize to other autistic behavioral problems associated with
      the vmPFC. 

PMID- 25070539
TI  - D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signalling
      to control synaptic plasticity and cocaine-induced responses.
AB  - Convergent dopamine and glutamate signalling onto the extracellular signal
      regulated kinase (ERK) pathway in medium spiny neurons (MSNs) of the striatum
      controls psychostimulant-initiated adaptive processes underlying long-lasting
      behavioural changes. We hypothesised that the physical proximity of dopamine D1
      (D1R) and glutamate NMDA (NMDAR) receptors, achieved through the formation of
      D1R/NMDAR complexes, may act as a molecular bridge that controls the synergistic
      action of dopamine and glutamate on striatal plasticity and behavioural responses
      to drugs of abuse. We found that concomitant stimulation of D1R and NMDAR drove
      complex formation between endogenous D1R and the GluN1 subunit of NMDAR.
      Conversely, preventing D1R/GluN1 association with a cell-permeable peptide (TAT
      GluN1C1) left individual D1R and NMDAR-dependent signalling intact, but prevented
      D1R-mediated facilitation of NMDAR-calcium influx and subsequent ERK activation.
      Electrophysiological recordings in striatal slices from mice revealed that
      D1R/GluN1 complexes control the D1R-dependent enhancement of NMDAR currents and
      long-term potentiation in D1R-MSN. Finally, intra-striatal delivery of TAT
      GluN1C1 did not affect acute responses to cocaine but reduced behavioural
      sensitization. Our findings uncover D1R/GluN1 complexes as a major substrate for
      the dopamine-glutamate interaction in MSN that is usurped by addictive drugs to
      elicit persistent behavioural alterations. They also identify D1R/GluN1 complexes
      as molecular targets with a therapeutic potential for the vast spectrum of
      psychiatric diseases associated with an imbalance between dopamine and glutamate
      transmission. 

PMID- 25070540
TI  - Histone deacetylase 3 promotes pancreatic cancer cell proliferation, invasion and
      increases drug-resistance through histone modification of P27, P53 and Bax.
AB  - Pancreatic cancer is one of the most aggressive solid malignancies with a dismal
      survival rate. Recent studies have shown that high expression levels of histone
      deacetylase 3 (HDAC3) correlate with malignant phenotype. However, the expression
      patterns and biological role of HDAC3 in pancreatic cancer remain unclear. In
      this study, our data showed that a higher level of HDAC3 protein expression was
      found in pancreatic cancer as compared to paired paracancerous tissues.
      Consistently, higher expression level of HDAC3 was found in all of the eight
      pancreatic cancer cell lines relative to human pancreatic ductal epithelial cells
      (HPDE). In addition, further function analysis revealed that HDAC3 can function
      as oncogenic protein, which could promote pancreatic cancer cell proliferation,
      migration and invasion, and may increase drug resistance. Moreover, the
      functional involvement of HDAC3 was partially correlated with post-induction
      repression of P53, P27 and Bax gene transcription, acting via H3K9 deacetylation.
      Taken together, our data suggest that HDAC3 participates in the pathogenesis and
      progression of pancreatic cancer through histone modification, which might be a
      pivotal epigenetic target against this devastating disease. 

PMID- 25070541
TI  - Receptor activator of nuclear factor-kappaB ligand and sclerostin expression in
      osteocytes of alveolar bone in rats with ligature-induced periodontitis.
AB  - BACKGROUND: Osteocytes are increasingly recognized as significant sources of
      osteoclast differentiation factor, receptor activator of nuclear factor-kappaB
      ligand (RANKL), and osteoblast differentiation inhibitory factor, sclerostin. In
      this study, RANKL and sclerostin expression of osteocytes is investigated in rats
      with ligature-induced periodontitis. METHODS: Rats were divided into control and
      periodontitis groups, and periodontitis was induced by ligature on the mandibular
      first molars. At 1, 3, 10, and 20 days after ligature, histologic analyses of
      alveolar bone (AB) and osteoid areas in the molar furcation were performed. The
      numbers of osteoclasts and RANKL- and sclerostin-positive osteocytes were
      estimated by tartrate-resistant acid phosphatase staining and
      immunohistochemistry, respectively. RESULTS: The AB area gradually decreased at
      day 10 after ligature and increased at day 20. The number of osteoclasts markedly
      increased at day 3 and then decreased. Conversely, osteoid formation was
      suppressed up to day 3 and then showed a remarkable increase above control level
      at day 20. The number of RANKL-positive osteocytes increased at days 1 and 3 and
      then decreased. Sclerostin-positive osteocytes markedly increased at days 3 and
      10 but decreased below control level at day 20. CONCLUSIONS: These results show
      that AB loss is accompanied by enhanced osteoclast formation and suppressed
      osteoid formation. Osteocytes express RANKL when osteoclast formation increases,
      and they express sclerostin when osteoid formation is suppressed. Conversely,
      osteocytic sclerostin expression decreases when osteoid formation increases.
      These findings suggest that osteocytes may be important in AB loss via RANKL and
      sclerostin expression in periodontitis.

PMID- 25070542
TI  - Congenital muscular dystrophy phenotype with neuromuscular spindles excess in a 5
      year-old girl caused by HRAS mutation.
AB  - We report on a 5-year-old girl who presented with an association of symptoms
      reminiscent of an Ullrich-like congenital muscular dystrophy including congenital
      hypotonia, proximal joint contractures, hyperlaxity of distal joints, normal
      cognitive development, and kyphoscoliosis. There was an excess of neuromuscular
      spindles on the skeletal muscle biopsy. This very peculiar feature on muscle
      biopsy has been reported only in patients with mutations in the HRAS gene.
      Sequence analysis of the subject's HRAS gene from blood leukocytes and skeletal
      muscle revealed a previously described heterozygous missense mutation (c.187G>A,
      p. Glu63Lys). The present report thus extends the differential diagnosis of
      congenital muscular dystrophy with major "retractile" phenotypes and adds
      congenital muscular dystrophy to the clinical spectrum of HRAS-related disorders.

PMID- 25070543
TI  - Guidelines for time-to-event end point definitions in sarcomas and
      gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative
      (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)?.
AB  - BACKGROUND: The use of potential surrogate end points for overall survival, such
      as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly
      common in randomized controlled trials (RCTs) in cancer. However, the definition
      of time-to-event (TTE) end points is rarely precise and lacks uniformity across
      trials. End point definition can impact trial results by affecting estimation of
      treatment effect and statistical power. The DATECAN initiative (Definition for
      the Assessment of Time-to-event End points in CANcer trials) aims to provide
      recommendations for definitions of TTE end points. We report guidelines for RCT
      in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried
      out a literature review to identify TTE end points (primary or secondary)
      reported in publications of RCT. An international multidisciplinary panel of
      experts proposed recommendations for the definitions of these end points.
      Recommendations were developed through a validated consensus method formalizing
      the degree of agreement among experts. RESULTS: Recommended guidelines for the
      definition of TTE end points commonly used in RCT for sarcomas and GIST are
      provided for adjuvant and metastatic settings, including DFS, TTF, time to
      progression and others. CONCLUSION: Use of standardized definitions should
      facilitate comparison of trials' results, and improve the quality of trial design
      and reporting. These guidelines could be of particular interest to research
      scientists involved in the design, conduct, reporting or assessment of RCT such
      as investigators, statisticians, reviewers, editors or regulatory authorities.

PMID- 25070544
TI  - Response to chemotherapy is not related to chromosome instability in synovial
      sarcoma.
AB  - BACKGROUND: Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite
      being considered as a chemosensitive disease, the real impact of perioperative
      chemotherapy on metastasis-free survival (MFS) is controversial. We have shown
      that metastatic relapse of SS is strongly associated with genomic complexity.
      There are no data regarding the potential correlation between genomic complexity
      and response to chemotherapy. PATIENTS AND METHODS: The study population included
      65 SS patients diagnosed between 1991 and 2013 and with available tissue
      material. Genomic profiling was carried out by using array-CGH. Forty-five SS out
      of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based
      chemotherapy. Radiological response was assessed according to RECIST criteria.
      Histological response was defined by the percentage of recognizable tumor cells
      on the surgical specimen. RESULTS: Genomic complexity was significantly
      associated with MFS. However, there was no statistically significant association
      between radiological or histological response and genomic complexity. CONCLUSION:
      The absence of significant association between response to chemotherapy and
      genomic complexity suggests that the prognostic value of chromosome instability
      in SS is independent of response to chemotherapy; mechanisms leading to
      metastatic relapse of SS are intrinsic to the biology of the tumor and current
      cytotoxic drugs are only poorly efficient to prevent it.

PMID- 25070545
TI  - Patients' preferences for subcutaneous trastuzumab versus conventional
      intravenous infusion for the adjuvant treatment of HER2-positive early breast
      cancer: final analysis of 488 patients in the international, randomized, two
      cohort PrefHer study.
AB  - BACKGROUND: Patients with HER2-positive early breast cancer (EBC) preferred
      subcutaneous (s.c.) trastuzumab, delivered via single-use injection device (SID),
      over the intravenous (i.v.) formulation (Cohort 1 of the PrefHer study:
      NCT01401166). Here, we report patient preference, healthcare professional
      satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where s.c.
      trastuzumab was delivered via hand-held syringe. PATIENTS AND METHODS: Patients
      were randomized to receive four adjuvant cycles of 600 mg fixed-dose s.c.
      trastuzumab followed by four cycles of standard i.v. trastuzumab, or vice versa.
      The primary endpoint was overall preference proportions for s.c. or i.v.,
      assessed by patient interviews in the evaluable ITT population. RESULTS: A total
      of 245 patients were randomized to receive s.c. followed by i.v. and 243 received
      i.v. followed by s.c. (evaluable ITT populations: 235 and 232 patients,
      respectively). s.c. was preferred by 415/467 [88.9%; 95% confidence interval (CI)
      85.7-91.6; P < 0.0001; two-sided test against null hypothesis of 65% s.c.
      preference]; 45/467 preferred i.v. (9.6%; 95% CI 7-13); 7/467 indicated no
      preference (1.5%; 95% CI 1-3). Clinician-reported adverse events occurred in
      292/479 (61.0%) and 245/478 (51.3%) patients during the pooled s.c. and i.v.
      periods, respectively (P < 0.05; 2 * 2 chi(2)); 16 patients (3.3%) in each period
      experienced grade 3 events; none were grade 4/5. CONCLUSIONS: PrefHer revealed
      compelling and consistent patient preferences for s.c. over i.v. trastuzumab,
      regardless of SID or hand-held syringe delivery. s.c. was well tolerated and
      safety was consistent with previous reports, including the HannaH study
      (NCT00950300). No new safety signals were identified compared with the known i.v.
      profile in EBC. PrefHer and HannaH confirm that s.c. trastuzumab is a validated
      and preferred option over i.v. for improving patients' care in HER2-positive
      breast cancer. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT01401166.

PMID- 25070546
TI  - A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib
      (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal
      cancer?.
AB  - BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530)
      improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.
      PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or
      primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of
      weekly paclitaxel (wPxl; 80 mg/m(2)/week *6 with 2-week break) plus saracatinib
      (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until
      disease progression. Patients were stratified by taxane-free interval (<6 versus
      >=6 months/no prior taxane). The primary end point was progression-free survival
      (PFS) rate at 6 months. Secondary end points included overall survival (OS) and
      response rate (RR). RESULTS: A total of 107 patients, median age 63 years, were
      randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6
      month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS
      was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54;
      P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P
      value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most
      frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo),
      abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile
      neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%).
      Response, PFS and OS were all significantly (P < 0.05) better in patients with
      taxane interval >=6 months/no prior taxane (n = 85) than those <6 months (n =
      22), regardless of randomisation. CONCLUSIONS: Saracatinib does not improve
      activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free
      interval of >=6 months/no prior taxane was associated with better outcome in both
      groups. TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

PMID- 25070548
TI  - A filter paper-based microdevice for low-cost, rapid, and automated DNA
      extraction and amplification from diverse sample types.
AB  - A plastic microfluidic device that integrates a filter disc as a DNA capture
      phase was successfully developed for low-cost, rapid and automated DNA extraction
      and PCR amplification from various raw samples. The microdevice was constructed
      by sandwiching a piece of Fusion 5 filter, as well as a PDMS
      (polydimethylsiloxane) membrane, between two PMMA (poly(methyl methacrylate))
      layers. An automated DNA extraction from 1 MUL of human whole blood can be
      finished on the chip in 7 minutes by sequentially aspirating NaOH, HCl, and water
      through the filter. The filter disc containing extracted DNA was then taken out
      directly for PCR. On-chip DNA purification from 0.25-1 MUL of human whole blood
      yielded 8.1-21.8 ng of DNA, higher than those obtained using QIAamp(r) DNA Micro
      kits. To realize DNA extraction from raw samples, an additional sample loading
      chamber containing a filter net with an 80 MUm mesh size was designed in front of
      the extraction chamber to accommodate sample materials. Real-world samples,
      including whole blood, dried blood stains on Whatman(r) 903 paper, dried blood
      stains on FTATM cards, buccal swabs, saliva, and cigarette butts, can all be
      processed in the system in 8 minutes. In addition, multiplex amplification of 15
      STR (short tandem repeat) loci and Sanger-based DNA sequencing of the 520 bp GJB2
      gene were accomplished from the filters that contained extracted DNA from blood.
      To further prove the feasibility of integrating this extraction method with
      downstream analyses, "in situ" PCR amplifications were successfully performed in
      the DNA extraction chamber following DNA purification from blood and blood stains
      without DNA elution. Using a modified protocol to bond the PDMS and PMMA, our
      plastic PDMS devices withstood the PCR process without any leakage. This study
      represents a significant step towards the practical application of on-chip DNA
      extraction methods, as well as the development of fully integrated genetic
      analytical systems. 

PMID- 25070547
TI  - Correcting oral contraceptive pharmacokinetic alterations due to obesity: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine if increasing the hormone dose or eliminating the hormone
      free interval improves key pharmacokinetic (PK) alterations caused by obesity
      during oral contraceptive (OC) use. STUDY DESIGN: Obese [body mass index
      (BMI)>=30 kg/m(2)], ovulatory, otherwise healthy, women received an OC containing
      20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) dosed cyclically (21
      days active pills with 7-day placebo week) for two cycles and then were
      randomized for two additional cycles to the following: continuous cycling (CC, a
      dose neutral arm using the same OC with no hormone-free interval) or increased
      dose (ID, a dose escalation arm using an OC containing 30 mcg EE/150 mcg LNG
      cyclically). During Cycles 2, 3 and 4, outpatient visits were performed to assess
      maximum serum concentration (Cmax), area under the curve (AUC0-infinity) and time
      to steady state as well as pharmacodynamics. These key PK parameters were
      calculated and compared within groups between baseline and treatment cycles.
      RESULTS: A total of 31 women enrolled and completed the study (CC group, n=16; ID
      group, n=15). Demographics were similar between groups [mean BMI: CC, 38 kg/m(2)
      (S.D. 5.1); ID, 41 kg/m(2) (S.D. 7.6)]. At baseline, the key LNG PK parameters
      were no different between groups; average time to reach steady state was 12 days
      in both groups; Cmax were CC: 3.82+/-1.28 ng/mL and ID: 3.13+/-0.87 ng/mL; and
      AUC0-infinity were CC: 267+/-115 h ng/mL and ID: 199+/-75 h ng/mL. Following
      randomization, the CC group maintained steady-state serum levels whereas the ID
      group had a significantly higher Cmax (p<.001) but again required 12 days to
      achieve steady state. However, AUC was not significantly different between CC
      (412+/-255 h ng/mL) and ID (283+/-130 h ng/mL). Forty-five percent (14/31) of the
      study population had evidence of an active follicle-like structure prior to
      randomization and afterwards this decreased to 9% (3/31). CONCLUSION: Both
      increasing the OC dose and continuous dosing appear to counteract the impact of
      obesity on key OC PK parameters. IMPLICATIONS: Obesity adversely affects the
      pharmacokinetics of very low dose OC pills. Although the impact of these changes
      on OC efficacy is still under debate, PK parameters can be normalized in obese
      users by continuous dosing or increasing to a low-dose pill.

PMID- 25070549
TI  - Quantitative analysis of a ubiquitin-dependent substrate using capillary
      electrophoresis with dual laser-induced fluorescence.
AB  - Protein degradation by the ubiquitin-proteasome system (UPS) affects many
      biological processes. Inhibition of the proteasome has emerged as a potential
      therapeutic target for cancer treatment. In this study, we developed a method for
      monitoring the degradation and accumulation of UPS-dependent substrates in cells
      using CE with dual LIF. We used a green fluorescent protein (GFP)-fusion of the
      ubiquitin substrate ribophorin 1 (GFP-RPN1) along with red fluorescent protein
      (RFP) as an internal control to normalize transfection efficiency. Determination
      of GFP-RPN1 and RFP in cell lysates were performed in an untreated capillary (75
      MUm * 50 cm) and 100 mM Tris-CHES buffer (pH 9.0) containing 10 mM SDS. GFP-RPN1
      and RFP fluorescence were detected at excitation wavelengths of 488 and 635 nm,
      and emission wavelengths of 520 and 675 nm, respectively, without any
      interference or crosstalk. The intensity of GFP-RPN1 fluorescence was normalized
      to that of RFP. Additionally, the proposed approach was used successfully to
      detect the degradation of GFP-RPN1 and evaluate proteasome inhibitors. These
      results show that the developed method is effective and promising for rapid and
      quantitative monitoring of UPS-dependent substrates compared to the current
      common methods, such as immunoblotting and pulse chase assays.

PMID- 25070551
TI  - Radiation risks from cardiovascular imaging tests.

PMID- 25070552
TI  - ECG response: July 29, 2014. Ventriculophasic arrhythmia,.

PMID- 25070550
TI  - Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction
      of triglyceride-rich apolipoprotein B lipoproteins through both low-density
      lipoprotein receptor-dependent and -independent mechanisms.
AB  - BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the
      degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its
      deficiency in humans results in low plasma LDL cholesterol and protection against
      coronary heart disease. Recent evidence indicates that PCSK9 also modulates the
      metabolism of triglyceride-rich apolipoprotein B (apoB) lipoproteins, another
      important coronary heart disease risk factor. Here, we studied the effects of
      physiological levels of PCSK9 on intestinal triglyceride-rich apoB lipoprotein
      production and elucidated for the first time the cellular and molecular
      mechanisms involved. METHODS AND RESULTS: Treatment of human enterocytes (CaCo-2
      cells) with recombinant human PCSK9 (10 MUg/mL for 24 hours) increased cellular
      and secreted apoB48 and apoB100 by 40% to 55% each (P<0.01 versus untreated
      cells), whereas short-term deletion of PCSK9 expression reversed this effect.
      PCSK9 stimulation of apoB was due to a 1.5-fold increase in apoB mRNA (P<0.01)
      and to enhanced apoB protein stability through both LDLR-dependent and LDLR
      independent mechanisms. PCSK9 decreased LDLR protein (P<0.01) and increased
      cellular apoB stability via activation of microsomal triglyceride transfer
      protein. PCSK9 also increased levels of the lipid-generating enzymes FAS, SCD,
      and DGAT2 (P<0.05). In mice, human PCSK9 at physiological levels increased
      intestinal microsomal triglyceride transfer protein levels and activity
      regardless of LDLR expression. CONCLUSIONS: PCSK9 markedly increases intestinal
      triglyceride-rich apoB production through mechanisms mediated in part by
      transcriptional effects on apoB, microsomal triglyceride transfer protein, and
      lipogenic genes and in part by posttranscriptional effects on the LDLR and
      microsomal triglyceride transfer protein. These findings indicate that targeted
      PCSK9-based therapies may also be effective in the management of postprandial
      hypertriglyceridemia.

PMID- 25070553
TI  - The value of lung perfused blood volume computed tomography in selecting the
      target lesions for the effective treatment of chronic thromboembolic pulmonary
      hypertension.

PMID- 25070554
TI  - Searching for the culprit vessel in acute myocardial infarction beyond
      angiography: role of cardiac magnetic resonance.

PMID- 25070555
TI  - Cardiology patient page. Prevention of acute rheumatic fever and rheumatic heart
      disease.

PMID- 25070556
TI  - Letter by Abergel and Chauvel regarding article, "Flow-gradient patterns in
      severe aortic stenosis with preserved ejection fraction: clinical characteristics
      and predictors of survival".

PMID- 25070557
TI  - Response to letter regarding article, "Flow-gradient patterns in severe aortic
      stenosis with preserved ejection fraction: clinical characteristics and
      predictors of survival".

PMID- 25070558
TI  - Letter by Jansen and van Royen regarding article, "Monitoring of monocyte
      recruitment in reperfused myocardial infarction with intramyocardial hemorrhage
      and microvascular obstruction by combined fluorine-19 and proton cardiac magnetic
      resonance imaging".

PMID- 25070559
TI  - Response to letter regarding article, "Monitoring of monocyte recruitment in
      reperfused myocardial infarction with intramyocardial hemorrhage and
      microvascular obstruction by combined fluorine 19 and proton cardiac magnetic
      resonance imaging".

PMID- 25070561
TI  - Short asymmetric synthesis of phenanthroindolizidines through chiral homoallylic
      sulfinamines.
AB  - An efficient stereocontrolled preparation of chiral phenanthroindolizidines is
      detailed. The synthesis relies on the stereoselective indium-mediated allylation
      of 2-(phenanthren-9-yl)acetaldehyde derivatives with chiral tert
      butylsulfinamide. Chemoselective transformations from the corresponding
      homoallylic sulfinamine allow the synthesis of the phenanthroindolizidines in
      only three synthetic operations, without any detectable racemization. Following
      this procedure, the synthesis of natural (-)-tylophorine was successfully
      accomplished. 

PMID- 25070562
TI  - Preictal surrender of post-spike slow waves to spike-related high-frequency
      oscillations (80-200 Hz) is associated with seizure initiation.
AB  - OBJECTIVE: Spike and slow waves consist of a "spike" including high-frequency
      oscillations (HFOs), which are linked to epileptogenicity and a "post-spike slow
      wave (PSS)" related to inhibitory activity. The aim of this study was to
      elucidate the spatiotemporal relationship between spike-related HFOs and PSS in
      patients with focal cortical dysplasia (FCD) type II. METHODS: We studied 10
      pediatric patients with FCD type II, who underwent extraoperative video
      electroencephalography (EEG). We selected spike and slow waves, which included
      HFOs (80-200 Hz), and performed spike peak-locked averaging 10 times during both
      30 s interictal (>1 h apart from seizures) and 30 s preictal periods. We
      calculated the power of spike-related HFOs and PSS during both periods for the
      following three areas: (1) inside the seizure-onset zone (SOZ), (2) inside the
      resection area (RA) but outside SOZ (RA-SOZ), and (3) outside the RA. Between the
      interictal and preictal periods we performed correlation (Spearman's coefficient)
      and simple linear regression analyses comparing HFO and PSS power within each
      area. RESULTS: A total of 1,614 averaged spike and slow waves were analyzed
      during both periods. During the interictal periods, there were significant
      positive correlations between HFO and PSS power in all areas (inside SOZ, r =
      0.568; RA-SOZ, r = 0.700; outside RA, r = 0.320). During the preictal periods,
      the correlation became weaker inside SOZ (r = 0.149) and remained unchanged both
      inside the RA-SOZ (r = 0.704) and outside RA (r = 0.346). From the interictal to
      preictal period, the slope (DeltaPSS power/DeltaHFO power) of the simple
      regression line decreased inside SOZ (0.349 to 0.051) but increased in RA-SOZ
      (0.534 to 0.734) and outside RA (0.267 to 0.435). SIGNIFICANCE: Relative power
      reduction of PSS to spike-related HFOs in SOZ is relevant for seizure initiation.
      Our analysis will contribute to future studies of seizure prediction and
      distinction between pathologic and physiologic HFOs. A PowerPoint slide
      summarizing this article is available for download in the Supporting Information
      section here.

PMID- 25070563
TI  - The role of strong electrostatic interactions at the dimer interface of human
      glutathione synthetase.
AB  - The obligate homodimer human glutathione synthetase (hGS) provides an ideal
      system for exploring the role of protein-protein interactions in the structural
      stability, activity and allostery of enzymes. The two active sites of hGS, which
      are 40 A apart, display allosteric modulation by the substrate gamma
      glutamylcysteine (gamma-GC) during the synthesis of glutathione, a key cellular
      antioxidant. The two subunits interact at a relatively small dimer interface
      dominated by electrostatic interactions between S42, R221, and D24. Alanine scans
      of these sites result in enzymes with decreased activity, altered gamma-GC
      affinity, and decreased thermal stability. Molecular dynamics simulations
      indicate these mutations disrupt interchain bonding and impact the tertiary
      structure of hGS. While the ionic hydrogen bonds and salt bridges between S42,
      R221, and D24 do not mediate allosteric communication in hGS, these interactions
      have a dramatic impact on the activity and structural stability of the enzyme.

PMID- 25070564
TI  - Expression and biochemical characterization of a thermophilic organic solvent
      tolerant lipase from Bacillus sp. DR90.
AB  - The objective of the present study was the isolation, molecular cloning and
      biochemical characterization of a thermophilic organic solvent-resistant lipase
      from Bacillus sp. DR90. The lipase gene was expressed in Escherichia coli
      BL21(DE3) using pET-28a(+) vector. The purification of recombinant lipase was
      conducted by nickel affinity chromatography and its biochemical properties were
      determined. The lipase sequence with an ORF of 639 bp contains the conserved
      pentapeptide Ala-His-Ser-Met-Gly. His-tagged recombinant lipase had a specific
      activity of 1,126 U/mg with a molecular mass of 26.8 kDa. The cloned lipase was
      optimally active at pH 8.0 and 75  degrees C representing high stability in broad
      ranges of temperature and pH. High performance liquid chromatography was used to
      determine the major compounds released during the lipase-catalyzed reaction of p
      nitrophenyl derivatives as well as the substrate specificity. The purified lipase
      showed high compatibility towards various organic solvents, surfactants and
      commercial solid/liquid detergents; therefore the recombinant DR90 lipase could
      be considered as a probable candidate for future applications, predominantly in
      detergent processing industries.

PMID- 25070565
TI  - Trigeminal laser-evoked potentials: a neurophysiological tool to detect post
      surgical outcome in trigeminovascular contact neuralgia.
AB  - BACKGROUND: The aim of this study was to explore the nociceptive system of
      patients affected by trigeminal neuralgia (TN) secondary to documented vascular
      contact who underwent microvascular decompression. For that purpose, we used the
      classical trigeminal reflexes and the trigeminal laser-evoked potentials (tLEPs)
      before and after surgery, in order to verify any possible change after
      decompression and determine if there was any correlation between the
      neurophysiological parameters and the clinical outcome. METHODS: Eleven patients
      affected by TN caused by trigeminovascular contact and 10 age-matched controls
      underwent conventional trigeminal reflexes (bilateral Blink Reflex/BR and
      Masseter Inhibitory Reflex stimulating infraorbital and mental nerves/MIR V2 and
      V3) and tLEPs. Patients repeated neurophysiological tests one week after surgery.
      RESULTS: Short-latency BR and MIR were normal in all patients before surgery and
      there was no statistical difference before and after surgery. Conversely, in
      patients before surgery, tLEPs' amplitudes were significantly lower in the
      affected than in the healthy side (p = 0.017 for V2 and 0.037 for V3 branches).
      After surgery, on the affected side, tLEP amplitude increased and the pre/post
      operative difference was significant (p = 0.017 for V2 and 0.028 for V3
      divisions). Nine patients referred satisfactory pain relief and the favourable
      clinical outcome correlated with the neurophysiological recovery. CONCLUSIONS:
      This study demonstrates that TN caused by trigeminovascular compression may be
      related to Adelta fibres impairment, and tLEPs are more sensitive than
      conventional trigeminal reflexes to reveal small fibre dysfunction and to monitor
      the post-surgical outcome in these patients.

PMID- 25070566
TI  - [The dangerous individual and the psychiatrist].

PMID- 25070567
TI  - [Criminogenic factors in sexually violent offenders detained by hospital order].
AB  - BACKGROUND: Up till now there have not been any publications about criminogenic
      factors in subgroups of sexually violent offenders detained by hospital order in
      the Netherlands. AIM: To perform an explorative study of criminogenic factors in
      16 child abusers, 22 rapists and 59 non-sexually violent inpatients detained by
      hospital order. METHOD: For our study we used a risk taxation instrument, a
      psychopathy check-list, Implicit Association Tests and self-report
      questionnaires. RESULTS: The child abuser group and the rapist group did not
      differ with regard to the risk of recidivism. The child abusers, however, scored
      lower on psychopathy and they associated submissiveness less with 'sexy' than the
      rapists did. When the three groups of offenders were compared, the child abusers
      and the rapists differed significantly from the non-sexually violent patients
      with regard to psychopathy. No differences were found between the three groups
      with regard to sexual preference, neuroticism, altruism, anger traits, hostility,
      and social skills. With regard to aggression, the child abusers scored lower than
      the rapists and the non-sexually violent patients. Furthermore, the child abusers
      reported more anxiety when voicing criticism than the non-sexually violent
      patients did. CONCLUSION: In view of the effect sizes of the differences found
      between the three groups, further research involving larger groups seems
      warranted. We also recommend that the svr-20 will be revised on the basis of a
      more valid factor structure. Rapists should be treated for both sexual and
      general violence.

PMID- 25070568
TI  - [Violent women: a multicentre study of the characteristics of female forensic
      psychiatric patients].
AB  - BACKGROUND: Violence perpetrated by women has attracted more and more attention
      in the past few years. However, there is lack of background information about
      women admitted to forensic psychiatric hospitals and about risk factors for
      recidivism. AIM: To conduct a multicenter study which will give more insight into
      female psychiatric patients and which will probably have implications for
      psychodiagnostics, risk assessment and treatment in (forensic) psychiatric
      settings. METHOD: We coded the files of 297 women who, between 1984 and 2013, had
      been admitted to one of four Dutch forensic psychiatric facilities by reason of
      violent delinquent behaviour. We used an extensive coding list and several risk
      assessment tools including the recently developed Female Additional Manual (fam)
      for women. RESULTS: The general picture that emerged was one of severely
      traumatised women with complex pathology and a high level of comorbidity. Many of
      the women had experienced previous treatment failures and had caused many
      incidents during treatment. CONCLUSION: Female forensic psychiatric patients are
      a complex group that deserves more specific attention. Attention for traumas from
      the past, intensive supervision in relationships and training for staff in
      dealing with, for instance, manipulative behaviour are the most important
      implications from this study.

PMID- 25070569
TI  - [Estimating and reporting aggression in relation to personal characteristics of
      emergency service workers].
AB  - BACKGROUND: Research on aggression in mental health care has focused mainly on
      patient characteristics, whereas very little research has been done on the
      characteristics of the care providers in their reporting of aggression. AIM: To
      study the characteristics of the care providers of an emergency service in
      relation to the reporting of aggression. METHOD: All emergency service workers( n
      = 21) in the Uden-Veghel region were asked to complete a neo-pi-r form. Before
      576 outreach contacts had been made with patients in psychiatric crises, the
      Checklist of Risks in the Crisis-team (crc) was also completed and in cases where
      the patient exhibited aggressive behaviour, a soas-r form was filled in,
      following contact with the patient. RESULTS: Significant differences were found
      between the psychiatric emergency service workers with regard to the mean
      estimates of the likelihood that they would experience aggression during the
      consultation and with regard to the proportion of patient contacts for which
      emergency workers reported aggression. There were indications that the level of
      conscientiousness of the emergency service workers was positively associated with
      a higher chance that they would report aggressive behaviour following the
      consultation. Furthermore, altruism was found to be negatively associated with
      the likelihood, as predicted by the service workers, that they would be
      confronted with aggression during contact with the patient. CONCLUSION: Possibly,
      workers who scored high on conscientiousness and who work thoroughly and in a
      orderly and systematic manner and who keep to the rules are less flexible in
      their response to the patient during the interaction. As a result, the patient
      became irritated more quickly. On the other hand, it could be that conscientious
      workers completed the form-filling more carefully when aggression had to be
      reported and as a result they made higher preliminary estimates of the likelihood
      of aggression and a reported a larger number of incidents of actual aggression.

PMID- 25070570
TI  - [The efficacy of psychological treatments for depression: a review of recent
      research findings].
AB  - BACKGROUND: Psychological treatments for depression have been shown to be
      effective, but there is room for improvement. AIM: To summarise new research
      findings concerning the efficacy of psychological treatments for depression, as
      reported in a recent dissertation. METHOD: Four systematic reviews and meta
      analyses and one randomised clinical trial are described. RESULTS: As has been
      shown in the case of patients treated with antidepressants, the efficacy of
      psychological treatments for depression when compared to strict control
      conditions, might be greater in patients with more severe depressive symptoms
      than in patients with milder symptoms. The efficacy of psychological treatments
      for depression when compared to control conditions is overestimated as a result
      of systematic publication of positive findings, as has been reported with regard
      to antidepressant medication too. There is increasing academic support for the
      efficacy of brief psychodynamic therapy for depression and there are no
      differences in the efficacy of short-term psychodynamic supportive psychotherapy
      and cognitive behavioural therapy for depression. Certain patient characteristics
      were found to be related to the differential efficacy of these two types of
      psychological treatments, but further validation is needed. A large number of
      patients with depression who seek help from second-line psychiatric clinics in
      the Netherlands fail to achieve remission following psychological treatment,
      irrespective of whether that treatment is combined with antidepressants.
      CONCLUSION: Improved efficacy of psychological treatments for depression is
      urgently needed and can be facilitated by means of high quality research.

PMID- 25070571
TI  - [Diagnosing psychiatric disorders in people with (very) mild intellectual
      disabilities].
AB  - BACKGROUND: There is a good chance that you, as a psychiatrist, will come in to
      contact with patients who have a borderline or mild intellectual disability (50 >
      iq < 85). Referral to specialised care is not always an option and may not always
      be necessary. However, diagnosing psychiatric disorders in these patients can
      present challenges. AIM: To increase our knowledge about the diagnosing of
      psychiatric disorders in people with borderline or mild intellectual
      disabilities. METHOD: In this article we describe some key considerations in
      making a diagnosis or a differential diagnosis of psychiatric disorders in people
      with an intellectual disability. RESULTS/ In the differential diagnosis of
      psychiatric symptoms and behavioral problems in persons with a
      RESULTS/CONCLUSION: borderline or mild intellectual disability, one needs to take
      into account the patient's cognitive and social emotional level and any possible
      underlying somatic conditions; in addition, one must search for the cause of the
      intellectual disability paying attention to the context and the facilities
      offered by the care system.

PMID- 25070572
TI  - [Feasibility and effectiveness of mindfulness training in adults with ADHD: a
      pilot study].
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a developmental
      disorder that often continues into adulthood. Stimulant medication is the common
      treatment for ADHD. However, there is a need for psychosocial interventions in
      addition to medication. AIM: To conduct a pilot study which examines the
      feasibility and effectiveness of mindfulness training for adults with ADHD.
      METHOD: Eleven adults with ADHD participated in a mindfulness training scheme
      lasting 10 weeks. ADHD symptoms, anxiety and depressive symptoms, quality of
      life, mindfulness skills and attentional tasks were measured before and after the
      period of mindfulness training. RESULTS: Nine participants completed the
      mindfulness training and were satisfied with the training. Eight of these
      reported improvement in their ADHD symptoms. For all participants, their quality
      of life, awareness of their actions and executive control had also improved.
      CONCLUSION: Mindfulness is a feasible treatment strategy for adults with ADHD and
      seems to have a positive effect on ADHD symptoms and executive control.

PMID- 25070573
TI  - Dielectric effect on the photovoltage loss in organic photovoltaic cells.
AB  - The VOC loss in several polymer-fullerene solar cells is determined. Based on
      these data, a major source of photovoltage loss is attributed to the low
      dielectric constants of the polymers. Such loss is close to zero if the
      dielectric constant of the polymer-fullerene blend is close to 5. 

PMID- 25070574
TI  - Light chain multiple myeloma, clinic features, responses to therapy and survival
      in a long-term study.
AB  - BACKGROUND: We intended to investigate the long-term clinical characteristics,
      responses to therapy and survival in patients with lightchain multiple myeloma
      (MM). METHODS: Ninety-six patients were enrolled into the study. There were 42
      kappa-chain MM patients and 54 lambda-chain MM patients. All the patients
      werestage III in the Durie-Salmonstaging system. Among them, 66 patients received
      Velcade (bortezomib) treatment and the other 30 did not. RESULTS: The main
      symptoms of these patients included bone pain (77.1%), weakness and fatigue
      (12.5%), foamy urine (8.3%) and extramedullaryplasmocytomas (33.3%). The overall
      response rate (ORR) was 95.5% in patients treated with Velcade and 60%in the
      patients without. The median survival times were 23 months in patients treated
      with Velcade and 12 months in patients without. The median time of progression
      free survival (PFS) was nine months in patients treated with Velcade and five
      months in patients without. The one-year PFS and two-year PFS were 37% and 25%,
      27% and 9% for patients treated with Velcade, or without, respectively. The three
      year overall survival (OS) and five-year OS were 33% and 24%, 28% and 9% for
      patients treated with Velcade, or without, respectively. There was no
      significance in OS between the two groups (P = 0.335). But there was significant
      difference in PFS between the two groups (P = 0.036). CONCLUSIONS: Our long-term
      study demonstrated that patients with lightchain myeloma appeared to have more
      aggressive disease courses and poor outcomes, which could be improved by
      treatment with Velcade.

PMID- 25070575
TI  - High rotation rate behavior of cervical spine segments in flexion and extension.
AB  - Numerical finite element (FE) models of the neck have been developed to simulate
      occupant response and predict injury during motor vehicle collisions. However,
      there is a paucity of data on the response of young cervical spine segments under
      dynamic loading in flexion and extension, which is essential for the development
      or validation of tissue-level FE models. This limitation was identified during
      the development and validation of the FE model used in this study. The purpose of
      this study was to measure the high rotation rate loading response of human
      cervical spine segments in flexion and extension, and to investigate a new tissue
      level FE model of the cervical spine with the experimental data to address a
      limitation in available data. Four test samples at each segment level from C2-C3
      to C7-T1 were dissected from eight donors and were tested to 10 deg of rotation
      at 1 and 500 deg/s in flexion and extension using a custom built test apparatus.
      There was strong evidence (p < 0.05) of increased stiffness at the higher
      rotation rate above 4 deg of rotation in flexion and at 8 deg and 10 deg of
      rotation in extension. Cross-correlation software, Cora, was used to evaluate the
      fit between the experimental data and model predictions. The average rating was
      0.771, which is considered to demonstrate a good correlation to the experimental
      data.

PMID- 25070576
TI  - Genetic identification of an oxyurid from a captive, black-handed spider monkey-
      implications for treatment and control.
AB  - Parasites are of major clinical significance in captive primates in zoos,
      particularly those with direct life cycles. Oxyurid nematodes can be a persistent
      problem, as infection intensity and environmental contamination with infective
      eggs are usually high. Observations at the Basel Zoo in Switzerland have revealed
      that particularly black-handed spider monkeys (Ateles geoffroyi) exhibit
      continuous oxyurid nematode infection(s), despite regular deworming with
      anthelmintics. In the present study, using a molecular approach, we were able to
      identify the nematode (Trypanoxyuris atelis) causing this ongoing problem, and we
      are now evaluating a practical treatment and control regimen to tackle this
      parasite problem. 

PMID- 25070577
TI  - Study of Myxosporea (Myxozoa), infecting worldwide mullets with description of a
      new species.
AB  - Existing data on Myxozoa parasites infecting mullets were reviewed. The validity
      of nine species names was updated. Sixteen species were registered during
      analysis of original material collected in the Mediterranean, Black, Azov, and
      Japan Seas in 2004-2005. A new bivalvulid myxozoan parasite, Myxobolus adeli n.
      sp., was described from the inner organs of the golden grey mullet Liza aurata
      (Risso, 1810) collected in the Mediterranean (Ebro Delta, Spain), Black Sea
      (Kerch Strait, Ukraine), and Azov Sea (Genichesk, Ukraine) coastal waters. It is
      characterized by the presence of elongated, spindle-like cysts 0.5-1.3 mm in
      size, filled with wide transverse-oval spores about 6.2 * 7.2 * 4.6 MUm in size,
      with two equal polar capsules measuring about 3.0 * 1.8 MUm and short polar
      filament, turned into four coils. The obtained data show that this species
      differs from all previously described Myxobolus spp. with equal polar capsules.
      Comparative study of Myxobolus spp. recorded in worldwide mullets indicates a
      close relationship with M. adeli n. sp. and Myxobolus improvisus Isjumova, 1964
      registered in mullets. Probably, the last species includes representatives of
      some different species, infecting freshwater and marine hosts.

PMID- 25070578
TI  - Comparison of infection success, development and swim bladder pathogenicity of
      two congeneric Anguillicola species in experimentally infected Anguilla anguilla
      and A. japonica.
AB  - Two closely related parasites, Anguillicola crassus and Anguillicola
      novaezelandiae, originally parasitizing swim bladders of the Japanese eel
      (Anguilla japonica and the Short-finned eel (Anguilla australis), respectively,
      were used for analyzing the infection success of each parasite species on either
      long-known, recently acquired or new definitive host species and the associated
      effects on the eels' swim bladders. On that account, European eels (Anguilla
      anguilla) and Japanese eels were experimentally infected with both Anguillicola
      species in the laboratory. Susceptibility of the two eel species to both parasite
      species was determined by analyses of infection data. Subsequently,
      histopathological effects of the nematodes on the hosts' swim bladders were
      characterized according to already established indices.The present study revealed
      significant differences between the four different host-parasite systems
      regarding recovery rates, infrapopulations, and damage levels. Both nematode
      species achieved significantly lower recovery rates in Japanese eels than in
      European eels, since the examined swim bladders of Japanese eels contained a high
      amount of dead encapsulated larvae, whereas those of European eels contained only
      living nematodes. Encapsulation of larvae in Japanese eels was associated with a
      distinct thickening of the swim bladder walls. The swim bladders of uninfected
      Japanese eels turned out to be generally thicker than those of European eels.
      Infection with both Anguillicola species resulted in a further thickening process
      of the swim bladder walls in Japanese eels, whereas those of European eels showed
      only minor changes. The two established classification systems turned out to be
      inapplicable, since the measurements and the macroscopic evaluations of the swim
      bladders of the two infected eel species did not entirely correspond to the
      underlying criteria. 

PMID- 25070579
TI  - Uncorrected refractive error and associated factors among primary school children
      in Debre Markos District, Northwest Ethiopia.
AB  - BACKGROUND: Uncorrected Refractive Error is one of the leading cause amblyopia
      that exposes children to poor school performance. It refrain them from productive
      working lives resulting in severe economic and social loses in their latter
      adulthood lives. The objective of the study was to assess the prevalence of
      uncorrected refractive error and its associated factors among school children in
      Debre Markos District. METHOD: A cross section study design was employed. Four
      hundred thirty two students were randomly selected using a multistage stratified
      sampling technique. The data were collected by trained ophthalmic nurses through
      interview, structured questionnaires and physical examinations. Snellens visual
      acuity measurement chart was used to identify the visual acuity of students.
      Students with visual acuity less than 6/12 had undergone further examination
      using auto refractor and cross-checked using spherical and cylindrical lenses.
      The data were entered into epi data statistical software version 3.1 and analyzed
      by SPSS version 20. The statistical significance was set at alpha <= 0.05.
      Descriptive, bivariate and multivariate analyses were done using odds ratios with
      95% confidence interval. RESULT: Out of 432 students selected for the study, 420
      (97.2%) were in the age group 7-15 years. The mean age was 12 +/- 2.1SD. Overall
      prevalence of refractive error was 43 (10.2%). Myopia was found among the most
      dominant 5.47% followed by astigmatism 1.9% and hyperopia 1.4% in both sexes.
      Female sex (AOR: 3.96, 95% CI: 1.55-10.09), higher grade level (AOR: 4.82, 95%
      CI: 1.98-11.47) and using computers regularly (AOR: 4.53, 95% CI: 1.58-12.96)
      were significantly associated with refractive error. CONCLUSION: The burden of
      uncorrected refractive errors is high among primary schools children. Myopia was
      common in both sexes. The potential risk factors were sex, regular use of
      computers and higher grade level of students. Hence, school health programs
      should work on health information dissemination and eye health care services
      provision.

PMID- 25070580
TI  - Scapular dyskinesis is detrimental to shoulder tendon properties and joint
      mechanics in a rat model.
AB  - Shoulder tendon injuries are frequently seen in the presence of abnormal scapular
      motion, termed scapular dyskinesis. The cause and effect relationship between
      scapular dyskinesis and shoulder injury has not been directly defined. We
      developed and used an animal model to examine the initiation and progression of
      pathological changes in the rotator cuff and biceps tendon. Sixty male Sprague
      Dawley rats were randomized into two groups: nerve transection (to induce
      scapular dyskinesis, SD) or sham nerve transection (control). The animals were
      euthanized 4 and 8 weeks after surgery. Shoulder function and passive joint
      mechanics were evaluated over time. Tendon mechanical, histological,
      organizational, and compositional properties were evaluated at both time points.
      Gross observation demonstrated alterations in scapular motion, consistent with
      scapular "winging." Shoulder function, passive internal range of motion, and
      tendon mechanical properties were significantly altered. Histology results,
      consistent with tendon pathology (rounded cell shape and increased cell density),
      were observed, and protein expression of collagen III and decorin was altered.
      This study presents a new model of scapular dyskinesis that can rigorously
      evaluate cause and effect relationships in a controlled manner. Our results
      identify scapular dyskinesis as a causative mechanical mechanism for shoulder
      tendon pathology.

PMID- 25070581
TI  - Activation of phosphatidylinositol 3-kinase/Akt signaling mediates sorafenib
      induced invasion and metastasis in hepatocellular carcinoma.
AB  - Sorafenib, an antiangiogenic agent, can promote tumor invasion and metastasis.
      The phosphatidylinositol 3-kinase (PI3K)/Akt/Snail-dependent pathway plays an
      important role in tumor invasion and metastasis. Yet, little is known concerning
      the role of the PI3K/Akt/Snail-dependent pathway in sorafenib-induced invasion
      and metastasis of hepatic carcinoma (HCC). A human HCC orthotopic xenograft model
      was established, and sorafenib (30 mg/kg/day) was administered orally. Tumor
      growth and intrahepatic metastasis were assessed, and immunohistochemistry was
      applied to analyze the activation of the PI3K/Akt/Snail-dependent pathway. HCC
      cell lines were treated with sorafenib (1, 5 and 10 uM), and proliferation,
      migration and invasion were assessed. Western blotting and real-time polymerase
      chain reaction (RT-PCR) were used to examine the related gene expression of
      epithelial-mesenchymal transition (EMT) markers and the PI3K/Akt/Snail-dependent
      pathway. Sorafenib inhibited tumor growth and promoted intrahepatic invasion and
      metastasis of the orthotopic tumors grown from SMMC7721-GFP cells in vivo.
      Additionally, sorafenib promoted EMT and invasion and metastasis of HCC cells in
      vitro. Importantly, sorafenib enhanced PI3K and Akt activation and upregulation
      of the expression of transcription factor Snail, a critical EMT mediator. The
      upregulation of transcription factor Snail expression by sorafenib may be related
      to activation of the PI3K/AKT signaling pathway. The PI3K/Akt/Snail-dependent
      pathway may mediate the pro-invasive and pro-metastatic effects of sorafenib on
      HCC by inducing EMT. 

PMID- 25070582
TI  - Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII
      deficiency undergoing surgical procedures.
AB  - BACKGROUND: Patients with congenital Factor XIII (FXIII) deficiency have impaired
      fibrin stabilization and are at high risk for surgical bleeding. Data regarding
      the use of FXIII concentrates before and during surgery are lacking. The
      objective of this study was to report the use of plasma-derived FXIII concentrate
      (Corifact in the United States; Fibrogammin P in other countries) in patients
      with congenital FXIII deficiency undergoing surgical procedures. STUDY DESIGN AND
      METHODS: FXIII concentrate at preoperative doses ranging from 25 to 40 U/kg was
      administered to six patients with congenital FXIII deficiency undergoing major or
      minor surgeries. RESULTS: FXIII concentrate was administered immediately before
      surgery for five surgical cases; three of these patients achieved excellent
      hemostasis during and after surgery, while two had intraoperative bleeding. In
      one surgical case, a regular prophylactic dose of FXIII concentrate was
      administered to the patient 1 week before minor surgery. FXIII concentrate
      provided rapid replacement of FXIII activity. In all but one of the patients
      given a dose of FXIII designed to increase FXIII levels more than 50%, there was
      satisfactory intraoperative and postoperative hemostasis. One patient undergoing
      aortic valve replacement on cardiopulmonary bypass (CPB) was the exception.
      Intraoperative bleeding in this patient was associated with lower-than-expected
      blood levels of FXIII. CONCLUSION: Preoperative plasma-derived FXIII concentrate
      allowed for sufficient hemostasis in most patients with FXIII deficiencies.
      Additional doses were necessary to achieve hemostasis in one patient who
      underwent a CPB procedure.

PMID- 25070583
TI  - Loss of internal backbone carbonyls: additional evidence for sequence-scrambling
      in collision-induced dissociation of y-type ions.
AB  - It is shown that y-type ions, after losing C-terminal H2O or NH3, can lose an
      internal backbone carbonyl (CO) from different peptide positions and yield
      structurally different product fragment ions upon collision-induced dissociation
      (CID). Such CO losses from internal peptide backbones of y-fragment ions are not
      unique to a single peptide and were observed in four of five model peptides
      studied herein. Experimental details on examples of CO losses from y-type
      fragment ions for an isotopically labeled AAAAHAA-NH2 heptapeptide and des
      acetylated-alpha-melanocyte-stimulating hormone (dalpha-MSH) (SYSMEHFRWGKPV-NH2)
      are reported. Results from isotope labeling, tandem mass spectrometry (MS(n)),
      and ion mobility-mass spectrometry (IM-MS) confirm that CO losses from different
      amino acids of m/z-isolated y-type ions yield structurally different ions. It is
      shown that losses of internal backbone carbonyls (as CID products of m/z-isolated
      y-type ions) are among intermediate steps towards formation of rearranged or
      permutated product fragment ions. Possible mechanisms for generation of the
      observed sequence-scrambled a-"like" ions, as intermediates in sequence
      scrambling pathways of y-type ions, are proposed and discussed. 

PMID- 25070584
TI  - Characterization of stress-exposed granulocyte colony stimulating factor using
      ELISA and hydrogen/deuterium exchange mass spectrometry.
AB  - Information on the higher-order structure is important in the development of
      biopharmaceutical drugs. Recently, hydrogen/deuterium exchange coupled with mass
      spectrometry (HDX-MS) has been widely used as a tool to evaluate protein
      conformation, and unique automated systems for HDX-MS are now commercially
      available. To investigate the potential of this technique for the prediction of
      the activity of biopharmaceuticals, granulocyte colony stimulating factor (G
      CSF), which had been subjected to three different stress types, was analyzed
      using HDX-MS and through comparison with receptor-binding activity. It was found
      that HDX-MS, in combination with ion mobility separation, was able to identify
      conformational changes in G-CSF induced by stress, and a good correlation with
      the receptor-binding activity was demonstrated, which cannot be completely
      determined by conventional peptide mapping alone. The direct evaluation of
      biological activity using bioassay is absolutely imperative in biopharmaceutical
      development, but HDX-MS can provide the alternative information in a short time
      on the extent and location of the structural damage caused by stresses.
      Furthermore, the present study suggests the possibility of this system being a
      versatile evaluation method for the preservation stability of biopharmaceuticals.

PMID- 25070585
TI  - Coherence and Consciousness: Study of Fronto-Parietal Gamma Synchrony in Patients
      with Disorders of Consciousness.
AB  - Evaluation of consciousness needs to be supported by the evidence of brain
      activation during external stimulation in patients with unresponsive wakefulness
      syndrome (UWS). Assessment of patients should include techniques that do not
      depend on overt motor responses and allow an objective investigation of the
      spontaneous patterns of brain activity. In particular, electroencephalography
      (EEG) coherence allows to easily measure functional relationships between pairs
      of neocortical regions and seems to be closely correlated with cognitive or
      behavioral measures. Here, we show the contribution of higher order associative
      cortices of patients with disorder of consciousness (N = 26) in response to
      simple sensory stimuli, such as visual, auditory and noxious stimulation. In all
      stimulus modalities an increase of short-range parietal and long-range fronto
      parietal coherences in gamma frequencies were seen in the controls and minimally
      conscious patients. By contrast, UWS patients showed no significant modifications
      in the EEG patterns after stimulation. Our results suggest that UWS patients can
      not activate associative cortical networks, suggesting a lack of information
      integration. In fact, fronto-parietal circuits result to be connectively
      disrupted, conversely to patients that exhibit some form of consciousness. In the
      light of this, EEG coherence can be considered a powerful tool to quantify the
      involvement of cognitive processing giving information about the integrity of
      fronto-parietal network. This measure can represent a new neurophysiological
      marker of unconsciousness and help in determining an accurate diagnosis and
      rehabilitative intervention in each patient. 

PMID- 25070586
TI  - Four years with FALCON - an ESTRO educational project: achievements and
      perspectives.
AB  - Variability in anatomical contouring is one of the important uncertainties in
      radiotherapy. FALCON (Fellowship in Anatomic deLineation and CONtouring) is an
      educational ESTRO (European SocieTy for Radiation and Oncology) project devoted
      to improve interactive teaching, the homogeneity in contouring and to compare
      individual contours with endorsed guidelines or expert opinions. This report
      summarizes the experience from the first 4 years using FALCON for educational
      activities within ESTRO School and presents the perspectives for the future.

PMID- 25070587
TI  - Efficacy of a compliant semicircular Ilizarov pin fixator module for treating
      infected nonunion of the femoral diaphysis.
AB  - Percutaneous transosseous Ilizarov wiring, whilst preferred in the tibia because
      of its unique properties, carries a high risk of complications in the femur. The
      aim of this work was to evaluate the efficacy of a more patient-friendly
      semicircular pin external fixator module built up from parts of the Ilizarov
      fixator components and its use in managing diaphyseal femoral nonunions. A group
      of 20 patients with infected diaphyseal nonunions of the femur after internal
      osteosynthesis were included in this study. The mean age of the patients at the
      time of surgery was 46 years (range 16-60, SD 15.6). The mean morbidity time
      since the original trauma was 10.2 months (range 6-15, SD 2.5). All the cases
      were fixed by the described external fixator module. Bony union with resolution
      of infection occurred in 18 (94.7 %) out of 19 cases after a mean period in the
      fixator of 11.2 months (range 8-18 SD 2.9). After a mean follow-up period of 3.5
      years (range 2-9, SD 2.6), there were 14 excellent, 3 good, 1 fair and 1 poor
      results from radiological evaluation and 10 excellent, 7 good, 1 fair and 1 poor
      results from functional assessment. In conclusion, the described semi-circular
      pin fixator module is patient-friendly and effective in managing infected
      nonunions of the femoral diaphysis. 

PMID- 25070588
TI  - Severe cutaneous adverse reactions in a local hospital setting: a 5-year
      retrospective study.
AB  - BACKGROUND: Severe cutaneous adverse reactions (SCAR) are rare but important
      causes of morbidity and mortality. Stevens-Johnson syndrome (SJS), Toxic
      Epidermal Necrolysis (TEN), and drug reaction with eosinophilia and systemic
      symptoms (DRESS) are severe cutaneous drug reactions that can be potentially life
      threatening. Our study aims to look at the epidemiology of SCAR in the local
      setting in Singapore and the underlying characteristics of our patients that may
      influence the drug reaction seen. METHODS: Data was collected retrospectively
      from in-patient records in the period of January 2007 to December 2011. We looked
      at several factors: (i) patient demographics including age, gender, ethnicity,
      comorbidities, (ii) culprit drug(s), (iii) latent period, (iv) drug reaction
      observed, (v) systemic complications, (vi) length of hospital stay, (vii)
      treatment given, and (viii) outcomes (mortality, morbidity). RESULTS: We
      collected data from 42 patients. The mean age of our patients was 51.8 years.
      Twenty-nine (69%) of the patients had underlying comorbidities. The most common
      culprit drug group was antibiotics. SJS was the most common SCAR observed
      (54.8%), followed by acute generalized exanthematous pustolosis (AGEP; 24%), TEN
      (11.9%), and DRESS (2%). Sixteen patients (38.1%) had complications, and there
      was one reported death. There was a weak correlation (correlation coefficient
      0.29, P value = 0.15, 95% CI = 2.07) between early steroid therapy and the length
      of stay. CONCLUSIONS: Antibiotics are the most common culprit drugs. The most
      common SCAR observed in our study was SJS. Early initiation of steroids may lead
      to a more favorable outcome.

PMID- 25070589
TI  - Sulforaphane down-regulates SKP2 to stabilize p27(KIP1) for inducing
      antiproliferation in human colon adenocarcinoma cells.
AB  - Sulforaphane is a cruciferous vegetable-derived isothiocyanate with promising
      chemopreventive and therapeutic activities. Induction of proliferation arrest and
      apoptosis principally contribute to sulforaphane's anticancer activity, but the
      precise molecular mechanisms remain elusive. The oncoprotein SKP2 is a key
      component of the SKP1-CULLIN1-F-box (SCF) E3 ligase complex and is responsible
      for directing SCF-mediated degradation of cyclin-dependent kinase inhibitor
      p27(KIP1) to promote cell proliferation. We herein provide the first evidence
      supporting the critical involvement of the SKP2-p27(KIP1) axis in sulforaphane
      induced antiproliferation in various human colon adenocarcinoma cell lines.
      Specifically, sulforaphane markedly suppressed the levels of bromodeoxyuridine
      (BrdU) incorporation and clonogenicity in all tested cell lines, illustrating the
      antiproliferative effect of sulforaphane. Of note, sulforaphane-induced
      antiproliferation was accompanied with down-regulation of SKP2, leading to the
      stabilization and thus up-regulation of p27(KIP1). Additionally, sulforaphane was
      found to down-regulate SKP2 mainly through transcriptional repression, as
      sulforaphane lowered SKP2 mRNA expression and the SKP2 promoter activity.
      Furthermore, sulforaphane treatment led to the activation of both AKT and ERK,
      thus ruling out the possibility that sulforaphane down-regulates SKP2 by
      inhibiting AKT or ERK. Notably, sulforaphane-elicited suppression of BrdU
      incorporation and clonogenicity were significantly rescued in the context of SKP2
      overexpression or p27(KIP1) depletion, therefore highlighting the important role
      of SKP2 down-regulation and the ensuing stabilization of p27(KIP1) in
      sulforaphane-induced antiproliferation. Collectively, these data expand our
      molecular understanding about how sulforaphane elicits proliferation arrest, but
      also implicate the application of sulforaphane in therapeutic modalities
      targeting SKP2. 

PMID- 25070590
TI  - Streamlining the imaging of clinically suspected pheochromocytoma: using urine
      metanephrines to decrease imaging costs.
AB  - PURPOSE: To improve the cost efficiency of the imaging evaluation of clinically
      suspected pheochromocytoma by using 24-hour fractionated urine metanephrine (FUM)
      results. METHODS: A retrospective review of I-123 meta-iodo-benzyl-guanidine
      single photon emission tomography (SPECT) computed tomography (CT) studies
      performed at our institution between January 2007 and February 2011 for
      clinically suspected pheochromocytoma was performed. SPECT-CT results from 70
      patients were compared with results from 24-hour FUM analysis (within 2 months of
      SPECT-CT) and with relevant CT or magnetic resonance imaging studies (within 6
      months of SPECT-CT). An imaging algorithm was developed to maximize cost
      efficiency without altering the final imaging interpretation. Actual imaging
      costs for the studied cohort were compared with the expected costs if this
      algorithm had been applied. RESULTS: If the 24-hour FUMs were normal, then all
      the SPECT-CT studies were negative (16/70). Eighty-seven percent of patients with
      abnormal total metanephrine had a positive SPECT-CT. If the total metanephrine
      was normal but 1 or more of the metanephrine fractions were abnormal, then 39%
      58% of the SPECT-CT studies were positive. Within this subgroup, none had a
      positive SPECT-CT if a CT or magnetic resonance image was negative or benign. The
      actual imaging costs averaged CAD$2833.19 per patient for this cohort. Applying a
      streamlined imaging algorithm guided by 24-hour FUM analysis would result in an
      average imaging cost of CAD$1225.97 per patient without an expected change in the
      final imaging impression. CONCLUSION: By using 24-hour FUM results to streamline
      imaging, considerable cost savings per patient (56.7%) can be attained without a
      change in the final overall imaging interpretation.

PMID- 25070591
TI  - Low-level laser therapy in IL-1beta, COX-2, and PGE2 modulation in partially
      injured Achilles tendon.
AB  - This study evaluated IL-1beta, COX-2, and PGE2 modulation in partially injured
      Achilles tendons treated with low-level laser therapy (LLLT). Sixty-five male
      Wistar rats were used. Sixty were submitted to a direct injury on Achilles tendon
      and then distributed into six groups: LASER 1 (a single LLLT application), LASER
      3 (three LLLT applications), and LASER 7 (seven LLLT applications) and Sham 1, 3,
      and 7 (the same injury but LLLT applications were simulated). The five remaining
      animals were allocated at control group (no procedure performed). LLLT (780 nm)
      was applied with 70 mW of mean power and 17.5 J/cm(2) of fluency for 10 s, once a
      day. The tendons were surgically removed and assessed immunohistochemically for
      IL-1beta, COX-2, and PGE2. In comparisons with control (IL-1beta: 100.5 +/- 92.5
      / COX-2: 180.1 +/- 97.1 / PGE2: 187.8 +/- 128.8) IL-1beta exhibited (mean +/- SD)
      near-normal level (p > 0.05) at LASER 3 (142.0 +/- 162.4). COX-2 and PGE2
      exhibited near-normal levels (p > 0.05) at LASER 3 (COX-2: 176.9 +/- 75.4 / PGE2:
      297.2 +/- 259.6) and LASER 7 (COX-2: 259.2 +/- 190.4 / PGE2: 587.1 +/- 409.7).
      LLLT decreased Achilles tendon's inflammatory process.

PMID- 25070592
TI  - A self-adaptive method for creating high efficiency communication channels
      through random scattering media.
AB  - Controlling the propagation of electromagnetic waves is important to a broad
      range of applications. Recent advances in controlling wave propagation in random
      scattering media have enabled optical focusing and imaging inside random
      scattering media. In this work, we propose and demonstrate a new method to
      deliver optical power more efficiently through scattering media. Drastically
      different from the random matrix characterization approach, our method can
      rapidly establish high efficiency communication channels using just a few
      measurements, regardless of the number of optical modes, and provides a practical
      and robust solution to boost the signal levels in optical or short wave
      communications. We experimentally demonstrated analog and digital signal
      transmission through highly scattering media with greatly improved performance.
      Besides scattering, our method can also reduce the loss of signal due to
      absorption. Experimentally, we observed that our method forced light to go around
      absorbers, leading to even higher signal improvement than in the case of purely
      scattering media. Interestingly, the resulting signal improvement is highly
      directional, which provides a new means against eavesdropping. 

PMID- 25070593
TI  - Burden of ambulatory visits and antibiotic prescribing patterns for adults with
      community-acquired pneumonia in the United States, 1998 through 2009.

PMID- 25070595
TI  - Overexpression of membrane proteins from higher eukaryotes in yeasts.
AB  - Heterologous expression and characterisation of the membrane proteins of higher
      eukaryotes is of paramount interest in fundamental and applied research. Due to
      the rather simple and well-established methods for their genetic modification and
      cultivation, yeast cells are attractive host systems for recombinant protein
      production. This review provides an overview on the remarkable progress, and
      discusses pitfalls, in applying various yeast host strains for high-level
      expression of eukaryotic membrane proteins. In contrast to the cell lines of
      higher eukaryotes, yeasts permit efficient library screening methods. Modified
      yeasts are used as high-throughput screening tools for heterologous membrane
      protein functions or as benchmark for analysing drug-target relationships, e.g.,
      by using yeasts as sensors. Furthermore, yeasts are powerful hosts for revealing
      interactions stabilising and/or activating membrane proteins. We also discuss the
      stress responses of yeasts upon heterologous expression of membrane proteins.
      Through co-expression of chaperones and/or optimising yeast cultivation and
      expression strategies, yield-optimised hosts have been created for membrane
      protein crystallography or efficient whole-cell production of fine chemicals. 

PMID- 25070594
TI  - Differential vulnerability of white matter structures to experimental infantile
      hydrocephalus detected by diffusion tensor imaging.
AB  - PURPOSE: The differential vulnerability of white matter (WM) to acute and chronic
      infantile hydrocephalus and the related effects of early and late reservoir
      treatment are unknown, but diffusion tensor imaging (DTI) could provide this
      information. Thus, we characterized WM integrity using DTI in a clinically
      relevant model. METHODS: Obstructive hydrocephalus was induced in 2-week-old
      felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1
      (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on
      neurological deficit. Hydrocephalic and age-matched control animals were
      sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic
      system, corpus callosum, and internal capsule prereservoir and every 3 weeks
      using DTI. Analyses were grouped as acute (<6 weeks) or chronic (>=6 weeks).
      RESULTS: In the corpus callosum during acute stages, fractional anisotropy (FA)
      decreased significantly with early and late reservoir placement (p = 0.0008 and
      0.0008, respectively), and diffusivity increased significantly in early (axial,
      radial, and mean diffusivity, p = 0.0026, 0.0012, and 0.0002, respectively) and
      late (radial and mean diffusivity, p = 0.01 and 0.0038, respectively) groups.
      Chronically, the corpus callosum was thinned and not detectable by DTI. FA was
      significantly lower in the optic chiasm and tracts (p = 0.0496 and 0.0052,
      respectively) with late but not early reservoir placement. In the internal
      capsule, FA in both reservoir groups increased significantly with age (p < 0.05)
      but diffusivity remained unchanged. CONCLUSIONS: All hydrocephalic animals
      treated with intermittent ventricular reservoir tapping demonstrated progressive
      ventriculomegaly. Both reservoir groups demonstrated WM integrity loss, with the
      CC the most vulnerable and the optic system the most resilient.

PMID- 25070596
TI  - Oral administration of whole dihomo-gamma-linolenic acid-producing Saccharomyces
      cerevisiae suppresses cutaneous inflammatory responses induced by croton oil
      application in mice.
AB  - Polyunsaturated fatty acids have been attracting considerable interest because of
      their many biological activities and important roles in human health and
      nutrition. Dihomo-gamma-linolenic acid (DGLA; C20: 3n-6) is known to have an anti
      inflammatory activity, but its range of effects was not well studied because of
      its limited natural sources. Taking advantage of genetic tractability and
      increasing wealth of accessible data of Saccharomyces cerevisiae, we have
      previously constructed a DGLA-producing yeast strain by introducing two types of
      desaturase and one elongase genes to convert endogenous oleic acid (C18:1n-9) to
      DGLA. In this study, we investigated the efficacy of oral intake of heat-killed
      whole DGLA-producing yeast cells in the absence of lipid purification on
      cutaneous inflammation. Topical application of croton oil to mouse ears induces
      ear swelling in parallel with the increased production of chemokines and
      accumulation of infiltrating cells into the skin sites. These inflammatory
      reactions were significantly suppressed in a dose-dependent manner by oral intake
      of the DGLA-producing yeast cells for only 7 days. This suppression was not
      observed by the intake of the gamma-linolenic acid-producing (C18:3n-6, an
      immediate precursor of DGLA) yeast, indicating DGLA itself suppressed the
      inflammation. Further analysis demonstrated that DGLA exerted an anti
      inflammatory effect via prostaglandin E1 formation because naproxen, a
      cyclooxygenase inhibitor, attenuated the suppression. Since 25-fold of purified
      DGLA compared with that provided as a form of yeast was not effective, oral
      administration of the whole DGLA-producing yeast is considered to be a simple but
      efficient method to suppress inflammatory responses.

PMID- 25070597
TI  - Medicinal properties of Hericium erinaceus and its potential to formulate novel
      mushroom-based pharmaceuticals.
AB  - Hericium erinaceus is an important mushroom with edible values and medicinal
      properties. Both the mycelium and the fruiting bodies contain many bioactive
      compounds with drug efficacy. Recent evidence demonstrates that it is helpful to
      various diseases, such as Alzheimer's disease, immunoregulatory, and many types
      of cancer. Furthermore, emerging pieces of evidence have shown that different
      active molecules in H. erinaceus have different functions on different organs in
      different diseases via the different mechanisms. Drawing on current research
      results, this review mainly focuses on the therapeutic effects of H. erinaceus on
      various diseases of multiple physiological systems, including the nervous system,
      digestive system, circulatory system, and immune system. This paper also
      discusses systematically the efficient protection of H. erinaceus against the
      diseases from the intricate experimental proofs by using the systematic
      viewpoints, which provides a framework for future research directions. 

PMID- 25070598
TI  - Development of an enhanced chromosomal expression system based on porin synthesis
      operon for halophile Halomonas sp.
AB  - Since halophile Halomonas spp. can grow contamination free in seawater under
      unsterile and continuous conditions, it holds great promise for industrial
      biotechnology to produce low-cost chemicals in an economic way. Yet, metabolic
      engineering methods are urgently needed for Halomonas spp. It is commonly known
      that chromosomal expression is more stable yet weaker than plasmid one is. To
      overcome this challenge, a novel chromosomal expression method was developed for
      halophile Halomonas TD01 and its derivatives based on a strongly expressed porin
      gene as a site for external gene integration. The gene of interest was inserted
      downstream the porin gene, forming an artificial operon porin-inserted gene. This
      chromosome expression system was proven functional by some examples: First,
      chromosomal expression of heterologous polyhydroxybutyrate (PHB) synthase gene
      phaC Re from Ralstonia eutropha completely restored the PHB accumulation level in
      endogenous phaC knockout mutant of Halomonas TD01. The integrated phaC Re was
      expressed at the highest level when inserted at the locus of porin compared with
      insertions in other chromosome locations. Second, an inducible expression system
      was constructed in phaC-deleted Halomonas TD01 by integrating the lac repressor
      gene (lacI) into the porin site in the host chromosome. The native porin promoter
      was inserted with the key 21 bp DNA of lac operator (lacO) sequence to become an
      inducible promoter encoded in a plasmid. This inducible system allowed on-off
      switch of gene expression in Halomonas TD strains. Thus, the stable and strong
      chromosomal expression method in Halomonas TD spp. was established.

PMID- 25070599
TI  - Machines that Go 'Ping': Medical Technology and Health Expenditures in OECD
      Countries.
AB  - Technology is believed to be a major determinant of increasing health spending.
      The main difficulty to quantify its effect is to find suitable proxies to measure
      medical technological innovation. This paper's main contribution is the use of
      data on approved medical devices and drugs to proxy for medical technology. The
      effects of these variables on total real per capita health spending are estimated
      using a panel model for 18 Organisation for Economic Co-operation and Development
      (OECD) countries covering the period 1981-2012. The results confirm the
      substantial cost-increasing effect of medical technology, which accounts for
      almost 50% of the explained historical growth of spending. Despite the overall
      net positive effect of technology, the effect of two subgroups of approvals on
      expenditure is significantly negative. These subgroups can be thought of as
      representing 'incremental medical innovation', whereas the positive effects are
      related to radically innovative pharmaceutical products and devices. A separate
      time series model was estimated for the USA because the FDA approval data in fact
      only apply to the USA, while they serve as proxies for the other OECD countries.
      Our empirical model includes an indicator of obesity, and estimations confirm the
      substantial contribution of this lifestyle variable to health spending growth in
      the countries studied.

PMID- 25070600
TI  - Lung transplantation from donors outside standard acceptability criteria--are
      they really marginal?
AB  - Lung transplantation (LTx) from "extended donor criteria" donors may reduce
      significantly organ shortage. However, its influence on results remains unclear.
      In this study, we evaluate retrospectively the results of LTx from donors outside
      standard criteria: PaO2/FiO2 ratio < 300 mmHg, age over 55 years, and history of
      smoking > 20 pack-years. Two hundred and forty-eight patients underwent first
      time LTx in our institution between January 2007 and January 2013. Seventy-nine
      patients (Group I) received organs from "extended donor criteria" and 169
      patients (Group II) from "standard donor criteria." Recipients' and donors'
      demographics, perioperative variables, and outcome were compared. Donors from
      Group I were significantly older [median (interquartile range)]: 52.5 (44;58) vs.
      42 (28.5;48.5) years (P < 0.001) with lower PaO2/FiO2 ratio: 366 +/- 116.1 455 +/
      80.5 mmHg (P < 0.001), higher incidence of smoking history: 57.7% vs. 41.8% (P =
      0.013), and more extensive smoking history: 24(15;30) vs. 10(3.75;14) pack-years
      (P < 0.001). Other parameters were comparable. Recipients' gender, diagnosis,
      percentage of patients operated on pump and receiving double LTx were also
      comparable. Recipients from Group I were significantly older: 50 (42;57) vs. 44
      (29.5;53.5) years (P = 001). There were no differences observed in recipients'
      prevalence of primary graft dysfunction (PGD) grade 3 over first three
      postoperative days, duration of mechanical ventilation, intensive care and
      hospital length of stay, prevalence of rejection, and bronchiolitis obliterans
      syndrome (BOS). 90-day, 1-year, and 5-year survival (Group I vs. II) were also
      similar: 88.6% vs. 91.7%, 83.2% vs. 84.6%, and 59% vs. 68.2% (log rank P =
      0.367). Carefully selected donor lungs from outside the standard acceptability
      criteria may expand existing donor pool with no detrimental effect on LTx
      outcome. 

PMID- 25070601
TI  - The clinical analgesic efficacy of buprenorphine.
AB  - WHAT IS KNOWN AND OBJECTIVE: Based on in vitro assays and select animal models,
      buprenorphine is commonly called a 'partial agonist'. An implication is that it
      should produce less analgesic effect in humans than so-called 'full agonists'
      such as morphine or fentanyl. However, buprenorphine has a multimechanistic
      pharmacology, and thus partial agonism at a specific receptor is not particularly
      relevant to its overall analgesic action. We review published clinical trials
      that directly compared the magnitude of buprenorphine's analgesic effect to
      analgesics commonly considered full agonists. COMMENT: Due to different signal
      transduction pathways, a drug can be a full agonist on one endpoint and a partial
      agonist on another. Therefore, we limited the present review to buprenorphine's
      analgesic effect. WHAT IS NEW AND CONCLUSION: Twenty-four controlled clinical
      trials were identified, plus a case report and dose-response curve. Based on
      complete or comparable pain relief, in buprenorphine had full clinical analgesic
      efficacy in 25 of the 26 studies.

PMID- 25070603
TI  - Reactive molecular simulations of protonation of water clusters and depletion of
      acidity in H-ZSM-5 zeolite.
AB  - Using reactive molecular dynamics (RMD), we present an atomistic insight into the
      interaction between water molecules and acidic centers of H-ZSM-5 zeolite. The
      reactive force field method, ReaxFF, was used to evaluate the adsorption and
      diffusion of water as well as to study the protonation of water molecules inside
      zeolite channels. The existing Si/Al/O/H parameters were refitted against DFT
      calculations to improve the ReaxFF description of interaction between water
      molecules and the acidic sites of zeolites. The diffusion coefficient of water in
      the zeolite obtained from refitted parameters is in excellent agreement with
      experimental results. The molecular dynamics (MD) simulations indicate that
      protonation of water molecules and acidity of the zeolite catalyst depend on
      water loadings and temperature and the observed trends compare favorably with
      existing experimental and theoretical studies. At higher water loadings,
      protonation of water molecules is more frequent leading to formation and growth
      of protonated water clusters inside zeolite channels. From the analysis of
      various reaction channels that were observed during the simulations, we found
      that such water clusters have relatively short life due to frequent interchange
      of protons and water molecules among the water clusters. Such proton hopping
      events play a key role in moving the protons between different acidic centers of
      zeolite. These simulations show the capability of ReaxFF in providing atomistic
      details of complex chemical interactions between the water phase and solid acid
      zeolites. 

PMID- 25070602
TI  - Non-targeted transcription factors motifs are a systemic component of ChIP-seq
      datasets.
AB  - BACKGROUND: The global effort to annotate the non-coding portion of the human
      genome relies heavily on chromatin immunoprecipitation data generated with high
      throughput DNA sequencing (ChIP-seq). ChIP-seq is generally successful in
      detailing the segments of the genome bound by the immunoprecipitated
      transcription factor (TF), however almost all datasets contain genomic regions
      devoid of the canonical motif for the TF. It remains to be determined if these
      regions are related to the immunoprecipitated TF or whether, despite the use of
      controls, there is a portion of peaks that can be attributed to other causes.
      RESULTS: Analyses across hundreds of ChIP-seq datasets generated for sequence
      specific DNA binding TFs reveal a small set of TF binding profiles for which
      predicted TF binding site motifs are repeatedly observed to be significantly
      enriched. Grouping related binding profiles, the set includes: CTCF-like, ETS
      like, JUN-like, and THAP11 profiles. These frequently enriched profiles are
      termed 'zingers' to highlight their unanticipated enrichment in datasets for
      which they were not the targeted TF, and their potential impact on the
      interpretation and analysis of TF ChIP-seq data. Peaks with zinger motifs and
      lacking the ChIPped TF's motif are observed to compose up to 45% of a ChIP-seq
      dataset. There is substantial overlap of zinger motif containing regions between
      diverse TF datasets, suggesting a mechanism that is not TF-specific for the
      recovery of these regions. CONCLUSIONS: Based on the zinger regions proximity to
      cohesin-bound segments, a loading station model is proposed. Further study of
      zingers will advance understanding of gene regulation.

PMID- 25070604
TI  - Uremic toxicity and sclerostin in chronic kidney disease patients.
AB  - BACKGROUND AND AIMS: Sclerostin is a circulating inhibitor of the Wnt/beta
      catenin pathway and may have a role in chronic kidney disease (CKD)-mineral and
      bone disorder. Blood sclerostin levels are known to be elevated in patients
      undergoing maintenance dialysis. The aims of the present study were to evaluate
      sclerostin levels in patients at different CKD stages and study potential
      associations between sclerostin levels and (i) biochemical parameters that are
      disturbed in CKD, (ii) markers of vascular disease and (iii) mortality. METHODS:
      One hundred and forty patients at CKD stages 2-5D were included in the present
      study. Routine clinical biochemistry tests and assays for sclerostin, protein
      bound uremic toxins (indoxylsulphate [IS] and p-cresyl sulphate [PCS]) and the
      toxin beta2 microglobulin (beta2M) were performed. Aortic and coronary
      calcification and arterial stiffness were assessed by multislice spiral computed
      tomography and pulse wave velocity measurements. The enrolled patients were
      prospectively monitored for mortality. RESULTS: Sclerostin levels were found to
      be elevated in CKD patients (especially those on hemodialysis). Furthermore,
      sclerostin levels were positively correlated with inflammation markers,
      phosphate, fibroblast growth factor 23, IS, PCS, beta2M and arterial stiffness. A
      multivariate linear regression analysis indicated that sclerostin levels were
      independently associated with IS, PCS and beta2M levels. Elevated serum
      sclerostin appeared to be associated with mortality (independently of age and
      inflammation). However, this association disappeared after adjustment for a
      propensity score including age, phosphate, interleukin-6, CKD stage and PCS.
      CONCLUSION: Our results indicate that sclerostin levels are elevated in CKD
      patients and are associated with inflammation, vascular lesions, uremia and
      (potentially) mortality.

PMID- 25070605
TI  - [Pleiotropic effects of sevelamer: a model of intestinal tract chelating agent].
AB  - The number of patients with chronic kidney disease (CKD) with its associated
      complications has increased dramatically worldwide in recent years. Therefore,
      many experimental and clinical studies have examined over the last decade the
      mechanisms involved, in order to explain the sharp increase in cardiovascular
      mortality. Hyperphosphatemia is a major problem in these patients especially at
      advanced stages of CKD, and it is associated with cardiovascular and mineral
      complications in these patients. Sevelamer is a phosphate binder that allows a
      better control of hyperphosphatemia, like other phosphate binder agents, but it
      has additional pleiotropic effects such as correcting certain abnormalities of
      lipid metabolism and clearance of several uremic toxins. These effects of
      sevelamer, restricted to the intestinal lumen, underline the importance of
      intestinal pathway in CKD and open the way to new therapeutic strategies for the
      management of the CKD and its complications. 

PMID- 25070606
TI  - Risk-treatment paradox of anticoagulation therapy in atrial fibrillation.

PMID- 25070607
TI  - Arginine vasopressin in heart failure.

PMID- 25070608
TI  - Enhanced oxygen separation through robust freeze-cast bilayered dual-phase
      membranes.
AB  - Dual-phase oxygen-permeable asymmetric membranes with enhanced oxygen permeation
      were prepared by combining freeze-casting, screen-printing, and constraint
      sintering techniques. The membranes were evaluated under oxyfuel operating
      conditions. The prepared membranes are composed of an original ice-templated
      La(0.6)Sr(0.4)Co(0.2)Fe(0.8)O(3-delta) support with hierarchically oriented
      porosity and a top fully densified bilayered coating comprising a 10 MUm-thick
      La(0.6)Sr(0.4)Co(0.2)Fe(0.8)O(3-delta) layer and a top protective 8 MUm-thick
      layer made of an optimized NiFe2O4/Ce(0.8)Tb(0.2)O(2-delta) composite synthesized
      by the one-pot Pechini method. Preliminary analysis confirmed the thermochemical
      compatibility of the three involved phases at high temperature without any
      additional phase detected. This membrane exhibited a promising oxygen permeation
      value of 4.8 mL min(-1)  cm(-2) at 1000  degrees C upon using Ar and air as the
      sweep and feed gases, respectively. Mimicking oxyfuel operating conditions by
      switching argon to pure CO2 as a sweep gas at 1000  degrees C and air as feed
      enabled an oxygen flux value of 5.6 mL min(-1)  cm(-2) to be reached. Finally,
      under the same conditions and increasing the oxygen partial pressure to 0.1 MPa
      in the feed, the oxygen permeation reached 12 mL min(-1)  cm(-2). The influence
      of CO2 content in the sweep gas was studied and its reversible and positive
      effect over oxygen permeation at temperatures equal to or above 950  degrees C
      was revealed. Finally, the membrane stability over a period of 150 h under CO2
      rich sweep gas showed a low degradation rate of 2.4*10(-2)  mL min(-1)  cm(-2)
      per day.

PMID- 25070609
TI  - Chemical vapor detection using a reconstituted insect olfactory receptor complex.
AB  - The sensing of vapor odorants is highly demanded in the field of life and medical
      sciences. Although olfactory receptors (ORs) have potentials to recognize
      volatile organic compounds, the interaction of ORs, chemical vapors, and peptide
      components in olfactory mucus has yet to be analyzed to develop OR-based sensors.
      A bioinspired electrophysiology technique is shown to record the response of
      reconstituted insect ORs to chemical vapors. To mimic the interface between ORs
      and olfactory mucus, OR expressing spheroids were loaded into a hydrogel
      microchamber array. A negative extracellular field potential shift of spheroids
      was successfully observed by the stimulation of their vapor cognate ligand.
      Importantly, the ligand repertoire of the OR of malaria vector mosquito examined
      by this method differed from that of in vivo studies. Our method is useful to
      develop protein-based gas sensing techniques and to examine the binding of ORs
      and chemical vapors. 

PMID- 25070610
TI  - The impact of psychiatric and extraintestinal comorbidity on quality of life and
      bowel symptom burden in functional GI disorders.
AB  - BACKGROUND: Functional gastrointestinal disorders (FGID) patients report poor
      health-related quality of life (HRQOL) and experience high rates of psychiatric
      and extraintestinal functional disorder (EIFD) comorbidity. The independent
      influence of these comorbidities on HRQOL and symptom burden remains unknown. We
      sought to determine whether FGID with mood or EIFD comorbidity have poorer HRQOL
      and greater GI symptom burdens; to determine the influence of comorbidities on
      HRQOL in FGID independent of bowel symptoms. METHODS: Subjects reported on
      comorbidities (anxiety, depression, somatization, EIFD), FGID criteria (irritable
      bowel syndrome, IBS; functional dyspepsia, FD) using ROME III Research
      questionnaire, GI symptom burden, and HRQOL. Differences in measures were
      assessed between subjects with and without ROME III criteria. Multiple regression
      determined the relative contribution of comorbidities to HRQOL, and mediation
      analysis explored whether comorbidity influences HRQOL. KEY RESULTS: In a cohort
      of 912 GI outpatients (47.2 +/- 1.5 years, 75.8% female), 606 (66.4%) met Rome
      III IBS and/or FD criteria. Comorbidities were common in FGID (>=1 in 77.4%),
      leading to lower HRQOL and greater GI symptom burden (each p < 0.05). Poorer
      HRQOL was predicted by both psychiatric and EIFD comorbidity (each p < 0.05)
      independent of GI symptoms (p < 0.001). Comorbidities together exerted a greater
      effect on predicted variation in HRQOL (70.9%) relative to GI symptoms (26.5%).
      CONCLUSIONS & INFERENCES: Psychiatric and EIFD comorbidities are common in FGID,
      decrease HRQOL and are associated with greater GI symptom burdens; these factors
      were stronger predictors of HRQOL than GI symptoms in FGID patients.

PMID- 25070612
TI  - [Dyspnea on exertion, angina pectoris and loud buzzing in the right groin in an
      82-year-old man].
AB  - We report on the case of an 82-year-old man who was suffering from chest pain and
      dyspnea. Acute cardiac ischemia could be excluded. Cardiac catheterization also
      revealed an aneurysm of the right common iliac artery. In addition, an
      arteriovenous fistula between the iliac artery and vein was detected by computer
      tomography angiography. Apparently, these symptoms were caused by a high output
      heart failure with known coronary heart disease. The patient was treated by
      implantation of prosthesis and oversewing the fistula which led to full recovery.

PMID- 25070611
TI  - [Incidental findings in gastroscopy and colonoscopy].
AB  - For many specific and nonspecific gastrointestinal symptoms, endoscopic
      diagnostic procedures play an important role. Gastroscopy and colonoscopy are
      easily available diagnostic and interventional procedures with low risk. The
      technical development of gastrointestinal endoscopy has led to an improvement in
      diagnostics and therapy. In addition to frequent and expected findings,
      incidental findings may occur. The incidental findings can distinguish rare
      diseases of unexpected diagnoses. Rare diagnoses usually require an
      individualized therapy. Unexpected diagnoses can take place during (not properly
      detected) or after an endoscopy (overlooked or newly appeared) occur. This
      overview deals with the question of how to minimize unexpected diagnoses and how
      to diagnose and treat incidental findings. 

PMID- 25070613
TI  - [Fever and right upper abdominal pain in a 26-year-old returning from travel
      abroad].
AB  - Persistent fever and unspecific general symptoms need a complete and detailed
      medical history and search for infection. We report on a case of amebiasis with
      liver abscesses of a 26-year-old man. He had stayed several weeks in India and
      South America. After being free of complaints for 4 months, unspecific general
      symptoms and fever appeared. Due to proven liver abscesses, a combination
      treatment was given. Within 12 days, he was free of symptoms and could be
      discharged.

PMID- 25070614
TI  - [Treatment of diseases acquired abroad].
AB  - Most imported diseases can be well treated-provided the diagnosis is made in due
      time. For example, only the rapid and correctly performed treatment of falciparum
      malaria can impede severe complications and save the patient's life. Effective
      treatments for amebiasis, giardiasis, leishmaniasis and worm diseases are
      available. However, it has to be mentioned that evidence from clinical trials is
      often insufficient. Accordingly only few international guidelines for imported
      diseases exist. 

PMID- 25070615
TI  - [Re-allign (randomized, phase II study to evaluate the safety and
      pharmacokinetics of oral dabigatran ftexilate in patients after heart valve
      replacement)].

PMID- 25070616
TI  - beta-Cell function in type 2 diabetes.
AB  - Different in vivo tests explore different aspects of beta-cell function. Because
      intercorrelation of insulin secretion indices is modest, no single in vivo test
      allows beta-cell function to be assessed with accuracy and specificity comparable
      to insulin sensitivity. Physiologically-based mathematical modeling is necessary
      to interpret insulin secretory responses in terms of relevant parameters of beta
      cell function. Models can be used to analyze intravenous glucose tests, but
      secretory responses to intravenous glucose may be paradoxical in subjects with
      diabetes. Use of oral glucose (or mixed meal) data may be preferable not only for
      simplicity but also for physiological interpretation. While the disposition index
      focuses on the relationship between insulin secretion and insulin resistance,
      secretion parameters reflecting the dynamic response to changing glucose levels
      over a time frame of minutes or hours--such as beta-cell glucose sensitivity--are
      key to explain changes in glucose tolerance and are largely independent of
      insulin sensitivity. Pathognomonic of the beta-cell defect of type 2 diabetes is
      a reduced glucose sensitivity, which is accompanied by normal or raised absolute
      insulin secretion rates--compensatory to the attendant insulin resistance--and
      impaired incretin-induced potentiation. As beta-cell mass is frequently within
      the range of nondiabetic individuals, these defects are predominantly functional
      and potentially reversible. Any intervention, on lifestyle or with drugs, that
      improves glucose tolerance does so primarily through increased beta-cell glucose
      sensitivity. So far, however, no intervention has proven unequivocally capable of
      modifying the natural course of beta-cell dysfunction.

PMID- 25070617
TI  - Trichomonas vaginalis: unusual presentation with ulcerative lesions.

PMID- 25070618
TI  - Relationship dimensions of the 'Down syndrome advantage'.
AB  - BACKGROUND: Some researchers have proposed an 'advantage' for parents of children
      with Down syndrome over parents of children with other intellectual disabilities,
      especially in relation to experiencing less parenting stress. Others have
      maintained that these differences are an artefact of demographic and related
      differences. This study extends the investigation of possible differences in
      dimensions of parenting stress and also examines whether differences exist in
      maternal and child contingent responsiveness during mother-child interaction in
      these two groups. METHOD: Mothers of children with Down syndrome (n = 43) and
      undifferentiated developmental disabilities (n = 54) completed measures of
      children's adaptive functioning and behaviour problems, parenting stress and
      maternal social support. Observers rated the contingent interactions between
      mothers and children using the Nursing Child Assessment Teaching Scale. RESULTS:
      Once mother's age, education and social support as well as child adaptive
      functioning and behaviour problems were considered, neither parent nor child
      related parenting stress demonstrated an advantage for parents of children with
      Down syndrome. However, a 'Down syndrome advantage' was apparent for both
      maternal and child contingent responsiveness after accounting for maternal
      demographic and contextual variables and child attributes. CONCLUSIONS: Children
      with Down syndrome and their mothers have more positive interactions than
      children with other developmental disabilities, both in terms of the
      responsiveness of mothers and of child responses contingent on maternal
      behaviour. These findings suggest that both children with Down syndrome
      themselves and their mothers are contributing to a Down syndrome advantage.

PMID- 25070619
TI  - Multifunctional superamphiphobic TiO2 nanostructure surfaces with facile
      wettability and adhesion engineering.
AB  - Compared to conventional top-down photo-cleavage method, a facile bottom-up ink
      combination method to in situ and rapidly achieve water wettability and adhesion
      transition, with a great contrast on the superamphiphobic TiO2 nanostructured
      film, is described. Moreover, such combination method is suitable for various
      kinds of superamphiphobic substrate. Oil-based ink covering or removing changes
      not only the topographical morphology but also surface chemical composition, and
      these resultant topographical morphology and composition engineering realize the
      site-selectively switchable wettability varying from superamphiphobicity to
      amphiphilicity, and water adhesion between sliding superamphiphobicity and sticky
      superamphiphobicity in micro-scale. Additionally, positive and negative micro
      pattern can be achieved by taking advantage of the inherent photocatalytic
      property of TiO2 with the assistance of anti-UV light ink mask. Finally, the
      potential applications of the site-selectively sticky superamphiphobic surface
      were demonstrated. In a proof-of-concept study, the microdroplet manipulation
      (storage, moving, mixing, and transfer), specific gas sensing, wettability
      template for positive and negative ZnO patterning, and site-selective cell
      immobilization have been demonstrated. This study will give an important input to
      the field of advanced functional material surfaces with special wettability. 

PMID- 25070620
TI  - Ab initio studies of propene epoxidation on oxidized silver surfaces.
AB  - Ab initio density functional simulations have been performed to study the
      adsorption of propene on partially oxidized silver surfaces and its interaction
      with surface oxygen. Two different adsorption conformations for propene are
      studied, with the molecule either intact or forming an Ag-C3H6-O oxymetallacycle
      (OMC) intermediate. Then, pathways for propene oxide, acrolein and propanone
      formation have been studied in detail, providing insight into the selectivity of
      the surfaces. We find that formation of acrolein must necessarily take place from
      OMC intermediates, requiring at least two neighbouring reactive surface oxygen
      anions. This suggests a strong relationship between the concentration of surface
      oxygen and the selectivity of these surfaces. 

PMID- 25070621
TI  - Effects of hospital-acquired conditions on length of stay for patients with
      diabetes.
AB  - BACKGROUND: Inpatients with diabetes have longer length of stays (LOS).
      Understanding patterns of in-hospital complications between patients with
      diabetes and others may reveal measures to improve patient welfare and minimise
      LOS. AIM: This study evaluates the rates and types of hospital-acquired
      conditions among patients with and without diabetes and assesses any effects on
      LOS. METHODS: A total of 47 615 admission episodes from The Northern Hospital
      over 12 months was reviewed. Episodes were divided into four groups: (i) patients
      without diabetes; (ii) patients with diabetes without end-organ sequelae (EOS);
      (iii) patients with diabetes with EOS; and (iv) a subset of non-diabetic patients
      with a Charlson Co-morbidity score >=1 (comparison group). The Classification of
      Hospital Acquired Diagnoses (CHADx) was applied to the groups to compare rates
      and types of inpatient complications. Linear regression was used to analyse the
      impact of the number of CHADx on LOS. RESULTS: Almost 30% of admissions of
      patients with diabetes and EOS had at least one CHADx, compared with 13% for non
      diabetes patients and 17% for the comparison group. The types of CHADx
      experienced by diabetes patients with EOS were similar to the comparison group.
      However, rates were 10 times higher. Linear regression demonstrated diabetes
      patients with EOS have increased LOS and each CHADx per episode has a larger
      effect on LOS. CONCLUSION: We demonstrate that diabetes patients have
      consistently higher rates of CHADx and longer LOS than similar patients with
      complex and chronic conditions. This provides a foundation for future studies to
      investigate preventative practices for this high-risk patient population.

PMID- 25070622
TI  - What clinicians wish to know about benign colorectal polyps: an operative
      classification.
AB  - INTRODUCTION: In recent years we assisted to a real "boom" of colorectal polyps,
      mainly due to the diffusion of screening procedures and of colonoscopy. This new
      "Polyp Epidemic" raises a series of problems and challenges. It became clear that
      many syndromes are defined by the number, histological type and location of
      polyps, together with extraintestinal manifestations and, in most cases, specific
      molecular changes. This paper discusses some of the above mentioned points,
      focusing on the relative role of endoscopists and pathologists. The objective is
      to reach an operative classification of the most common polyps observed in daily
      practice which might be of help for the identification of inherited syndromes.
      METHODS AND RESULTS: Six main histological types of polyps are defined and
      underlined: Adenoma, hyperplastic/serrated, hamartoma, ganglioneuroma, mixed,
      inflammatory. The importance of a brief description, in pathology reports, of
      each type of polyps is fundamental for a correct diagnosis. Each of the defined
      polyps is associated with inherited syndromes whose genetic basis has recently
      been elucidated. Relevant information should be given, and separated from
      additional (and not strictly necessary) information. RECOMMENDATIONS: A correct
      polyp analysis is a valuable element for identifying specific inherited
      syndromes. Polyps represent a precious tool for planning screening and follow-up
      in a given individual. In addition, these lesions focus the interest of
      clinicians toward syndrome which were considered as rare diseases; indeed, the
      explosion of molecular biology and the diffusion of colonoscopy revealed that
      these conditions are frequent and amenable of treatment.

PMID- 25070624
TI  - Organizing medical oncology care at a regional level and its subsequent impact on
      the quality of early breast cancer management: a before-after study.
AB  - BACKGROUND: One of the main measures of the French national cancer plan is to
      encourage physicians to work collectively, and to minimize territorial inequities
      in access to care by rethinking the geographical distribution of oncologists. For
      this reason, cancer care services are currently being reorganized at national
      level. A new infrastructure for multidisciplinary cancer care delivery has been
      put in place in our region. Patients can receive multidisciplinary health care
      services nearer their homes, thanks to a mobile team of oncologists. The
      objective of our study was to assess, using a quality approach, the impact on
      medical management and on the costs of treating early breast cancer, of the new
      regional structure for cancer care delivery. METHODS: Before-and-after study
      performed from 2007 to 2010, including patients treated for early breast cancer
      in three hospitals in the region of Franche-Comte in Eastern France. The main
      outcome measures were quality criteria, namely delayed treatment (>12 weeks),
      dose-intensity and assessment of adjuvant chemotherapy. Other outcomes were 24
      month progression-free survival (PFS) and economic evaluation. RESULTS: This
      study included 667 patients. The rate of chemotherapy tended to decrease, but not
      significantly (49.3% before versus 42.2% after, p=0.07), while the use of taxanes
      increased by 38% across all centres (59.6% before versus 98.0% after, p <
      0.0001). There was a non-significant reduction in the time between surgery and
      adjuvant chemotherapy (6.0 +/- 3.0 weeks before versus 5.6 +/- 3.6 weeks after,
      p=0.11). Dose-dense chemotherapy improved slightly, albeit non significantly
      (86.3% versus 91.1% p=0.22) and time to treatment tended to decrease. The new
      regional infrastructure did not change 24-month PFS, which remained at about 96%.
      The average cost of treatment was estimated at ? 7000, with no difference between
      the two periods. CONCLUSIONS: Despite a shortage of oncologists, the new
      organization put in place in our region for the provision of care for early
      breast cancer makes it possible to maintain local community-based treatment,
      without negative economic consequences. This new structure for cancer care
      delivery offers cancer services of similar quality with no modification of 24
      month PFS in early breast cancer.

PMID- 25070623
TI  - Test-retest reliability and validity of life-course alcohol consumption measures:
      the 2005 National Alcohol Survey follow-up.
AB  - BACKGROUND: Few studies assess reliability and validity of lifetime alcohol
      measures. We undertook extended test-retest analyses of retrospective lifetime
      drinking measures and of incremental predictive ability of lifetime heavy
      drinking (days 5+ drinks) in teens, 20s, and 30s for current (12-month) alcohol
      use disorders (AUDs). METHODS: A subset (31.4%; 962 men, 1,220 women) of the 2005
      U.S. National Alcohol Survey (NAS; N11) completed a follow-up survey (N11T) by
      phone or mail (mean delay of 2.7 years). Both surveys assessed lifetime drinking.
      RESULTS: In N11T, drinking status was reported consistently by 94.7% of N11
      current drinkers, 85.5% of ex-drinkers, and 74.4% of lifetime abstainers (93.5%
      overall). Cumulative number of prior heavy drinking days (teens through 30s) were
      moderately consistent (Pearson's rho = 0.6, p < 0.001, n = 1,636). Reliability
      was lower for younger respondents under 30 and higher for Whites versus Blacks
      and Hispanics (rho = 0.68 vs. rho = 0.56 vs. rho = 0.56, both p = 0.01), but did
      not differ by gender. Heavy drinking days in teens correlated 0.63 (p < 0.001)
      for those aged 20 or older, higher for women than men and for Whites versus
      ethnic minorities. Heavy drinking days in the 20s and 30s reported by those 30
      and older and 40 and older correlated at 0.63 and 0.67, respectively, being
      higher for Whites. Age of drinking onset and of lifetime maximum quantity reports
      were also consistent (0.65, 0.73), higher for women versus men, for those older
      than 29 versus younger, and for Whites versus Blacks and Hispanics. In N11,
      controlling for gender, age, ethnicity, and current 5+ frequency, cumulative
      prior 5+ days (teens to age 39) predicted current alcohol-related consequences
      and dependence (both p = 0.003). CONCLUSIONS: Measurements of earlier heavy
      drinking are feasible, efficient, and reasonably reliable, albeit with some
      individual imprecision. Prior drinking data improve prediction of current AUDs,
      adjusting for demographics and current drinking.

PMID- 25070625
TI  - Functional characterization of probiotic surface layer protein-carrying
      Lactobacillus amylovorus strains.
AB  - BACKGROUND: Adhesiveness to intestinal epithelium, beneficial immunomodulating
      effects and the production of pathogen-inhibitory compounds are generally
      considered as beneficial characteristics of probiotic organisms. We showed the
      potential health-promoting properties and the mechanisms of probiotic action of
      seven swine intestinal Lactobacillus amylovorus isolates plus the type strain
      (DSM 20531T) by investigating their adherence to porcine intestinal epithelial
      cells (IPEC-1) and mucus as well as the capacities of the strains to i) inhibit
      the adherence of Escherichia coli to IPEC-1 cells, ii) to produce soluble
      inhibitors against intestinal pathogens and iii) to induce immune signaling in
      dendritic cells (DCs). Moreover, the role of the L. amylovorus surface (S) 
      layers - symmetric, porous arrays of identical protein subunits present as the
      outermost layer of the cell envelope - in adherence to IPEC-1 cells was assessed
      using a novel approach which utilized purified cell wall fragments of the strains
      as carriers for the recombinantly produced S-layer proteins. RESULTS: Three of
      the L. amylovorus strains studied adhered to IPEC-1 cells, while four strains
      inhibited the adherence of E. coli, indicating additional mechanisms other than
      competition for binding sites being involved in the inhibition. None of the
      strains bound to porcine mucus. The culture supernatants of all of the strains
      exerted inhibitory effects on the growth of E. coli, Salmonella, Listeria and
      Yersinia, and a variable, strain-dependent induction was observed of both pro-
      and anti-inflammatory cytokines in human DCs. L. amylovorus DSM 16698 was shown
      to carry two S-layer-like proteins on its surface in addition to the major S
      layer protein SlpA. In contrast to expectations, none of the major S-layer
      proteins of the IPEC-1 -adhering strains mediated bacterial adherence.
      CONCLUSIONS: We demonstrated adhesive and significant pathogen inhibitory
      efficacies among the swine intestinal L. amylovorus strains studied, pointing to
      their potential use as probiotic feed supplements, but no independent role could
      be demonstrated for the major S-layer proteins in adherence to epithelial cells.
      The results indicate that many intestinal bacteria may coexist with and confer
      benefits to the host by mechanisms not attributable to adhesion to epithelial
      cells or mucus.

PMID- 25070626
TI  - Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular
      senescence.
AB  - Cellular senescence, which is known to halt proliferation of aged and stressed
      cells, plays a key role against cancer development and is also closely associated
      with organismal aging. While increased insulin-like growth factor (IGF) signaling
      induces cell proliferation, survival and cancer progression, disrupted IGF
      signaling is known to enhance longevity concomitantly with delay in aging
      processes. The molecular mechanisms involved in the regulation of aging by IGF
      signaling and whether IGF regulates cellular senescence are still poorly
      understood. In this study, we demonstrate that IGF-1 exerts a dual function in
      promoting cell proliferation as well as cellular senescence. While acute IGF-1
      exposure promotes cell proliferation and is opposed by p53, prolonged IGF-1
      treatment induces premature cellular senescence in a p53-dependent manner. We
      show that prolonged IGF-1 treatment inhibits SIRT1 deacetylase activity,
      resulting in increased p53 acetylation as well as p53 stabilization and
      activation, thus leading to premature cellular senescence. In addition, either
      expression of SIRT1 or inhibition of p53 prevented IGF-1-induced premature
      cellular senescence. Together, these findings suggest that p53 acts as a
      molecular switch in monitoring IGF-1-induced proliferation and premature
      senescence, and suggest a possible molecular connection involving IGF-1-SIRT1-p53
      signaling in cellular senescence and aging. 

PMID- 25070627
TI  - Chemical inhibitors of CYP450 enzymes in liver microsomes: combining selectivity
      and unbound fractions to guide selection of appropriate concentration in
      phenotyping assays.
AB  - 1. Chemical inhibition is the widely used method in reaction phenotyping assays
      for estimation of specific enzyme contribution to a given metabolic pathway. The
      results from phenotyping assays depend on the selectivity of chemical inhibitor
      and the concentration of inhibitor used in the incubation. 2. The higher protein
      concentrations used in the in vitro phenotyping assays will impact the inhibitory
      potency of chemical inhibitors. The objective of the study is to evaluate
      comprehensively the selectivity of chemical inhibitors and to guide in selecting
      appropriate concentration of the chemical inhibitors to be used in the
      phenotyping assays based on unbound fractions. 3. Selectivity of chemical
      inhibitors against nine major CYP450 isoforms was determined in liver microsomes
      using standard probe substrates. The unbound fractions of the selective
      inhibitors were determined in human liver microsomes using high-throughput
      equilibrium dialysis. Combining unbound inhibitor concentrations that are
      required to inhibit the CYP450 activities by 90% and unbound fractions of the
      chemical inhibitors in liver microsomes appropriate total concentrations of the
      inhibitors to be used in the phenotyping assays were reported. 4. The findings
      suggest that non-specific binding of the chemical inhibitors need to be taken
      into account while selecting concentrations for phenotyping assays.

PMID- 25070629
TI  - Commentary: from normal scientific progress to game changers: the impact on
      periodontal clinical practice.

PMID- 25070628
TI  - Survivin depletion inhibits tumor growth and enhances chemosensitivity in
      hepatocellular carcinoma.
AB  - Survivin is a member of the inhibitor of apoptosis family, which has been
      suggested to be crucial in the control of cell division and inhibition of
      apoptosis. Expression of this protein has been observed in transformed cell lines
      and human tumor tissues, including those from colorectal cancer, but not in
      terminally differentiated adult tissues. Survivin mRNA expression has frequently
      been detected in hepatocellular carcinoma (HCC) and its protein expression has
      been demonstrated to be highly correlated with proliferation index rather than
      apoptotic index. The present study aimed to analyze the effect of survivin on the
      tumorigenicity and chemosensitivity of HCC via the establishment of an HCC cell
      line (PLC/PRF/5) with the stable knockdown of the survivin gene (PLC-k3). This
      cell line displayed significantly lower rates of survival and proliferation in
      assays of cell viability and proliferation, respectively, compared with those of
      the control cell line (PLC-v). In addition, PLC-k3 cells were more sensitive to
      cisplatin treatment, resulting in S phase arrest. These findings were further
      confirmed by an in vivo experiment. The data of the present study suggest that
      survivin is critical in promoting cell proliferation but not in inhibition of
      apoptosis, and enhances the chemosensitivity of HCC. Thus, the suppression of
      survivin expression in combination with cisplatin may contribute to the
      development of more effective treatments for HCC.

PMID- 25070631
TI  - Over-shunting associated myelopathy.
AB  - Intracranial hypotension typically presents following cerebrospinal fluid (CSF)
      leak, but can be induced by CSF diversion. Classically, patients present with
      positional headache, but less common symptoms include neck pain and cranial nerve
      palsies. To our knowledge, the neurosurgical literature contains six reports of
      patients with symptomatic cervical, epidural venous plexus engorgement as the
      result of CSF shunting. The patient presented herein is a 26-year-old woman with
      shunt-dependent, congenital hydrocephalus. She presented with rapidly progressive
      cervical myelopathy following ventriculoperitoneal shunt revision. Imaging
      revealed engorgement of the cervical epidural venous plexus and mass effect on
      the cervical spinal cord. "Over-shunting associated myelopathy" is a rare
      complication of CSF diversion that should be familiar to physicians who routinely
      evaluate patients with intracranial shunts. 

PMID- 25070632
TI  - Persistent trigeminal artery supply to an intrinsic trigeminal nerve
      arteriovenous malformation: a rare cause of trigeminal neuralgia.
AB  - Infratentorial arteriovenous malformations (AVM) associated with the trigeminal
      nerve root entry zone are a known cause of secondary trigeminal neuralgia (TN).
      The treatment of both TN and AVM can be challenging, especially if the AVM is
      embedded within the trigeminal nerve. A persistent trigeminal artery (PTA) can
      rarely supply these intrinsic trigeminal nerve AVM. We present a 64-year-old man
      with TN from a right trigeminal nerve AVM supplied by a PTA variant. The patient
      underwent microvascular decompression and a partial resection of the AVM with
      relief of facial pain symptoms. His residual AVM was subsequently treated with
      CyberKnife radiosurgery (Accuray, Sunnyvale, CA, USA). A multimodality approach
      may be required for the treatment of trigeminal nerve associated PTA AVM and
      important anatomic patterns need to be recognized before any treatment. Herein,
      we report to our knowledge the third documented patient with a posterior fossa
      AVM supplied by a PTA and the first PTA AVM presenting as facial pain. 

PMID- 25070633
TI  - Bow hunter's syndrome secondary to bilateral dynamic vertebral artery
      compression.
AB  - Bow hunter's syndrome is a condition in which vertebrobasilar insufficiency is
      resultant from head rotation, clinically manifested by presyncopal sensation,
      syncope, dizziness, and nausea. It is usually diagnosed clinically, with
      supporting vascular imaging demonstrating an occluded or at the very least
      compromised unilateral vertebral artery, while the dominant vertebral artery
      remains patent in the neutral position. Dynamic imaging is utilized to confirm
      the rotational compression of the dominant vertebral artery. We present the rare
      case of a patient with typical Bow hunter's symptoms, bilaterally patent
      vertebral arteries on neutral imaging, and bilateral compromise with head
      rotation. Our patient underwent posterior decompression of the culprit atlanto
      axial transverse foramen and subaxial cervical fusion, with resolution of his
      symptoms. Our patient exemplifies the possibility of bilateral dynamic vertebral
      artery occlusion. We show that Bow hunter's syndrome cannot be ruled out in the
      setting of bilaterally patent vertebral arteries on neutral imaging and that
      severe cervical spondylosis should impart further clinical suspicion of this
      unusual phenomenon. 

PMID- 25070634
TI  - Informative Bayesian Model Selection: a method for identifying interactions in
      genome-wide data.
AB  - In high-dimensional genome-wide (GWA) data, a key challenge is to detect genomic
      variants that interact in a nonlinear fashion in their association with disease.
      Identifying such genomic interactions is important for elucidating the
      inheritance of complex phenotypes and diseases. In this paper, we introduce a new
      computational method called Informative Bayesian Model Selection (IBMS) that
      leverages correlation among variants in GWA data due to the linkage
      disequilibrium to identify interactions accurately in a computationally efficient
      manner. IBMS combines several statistical methods including canonical correlation
      analysis, logistic regression analysis, and a Bayesians statistical measure of
      evaluating interactions. Compared to BOOST and BEAM that are two widely used
      methods for detecting genomic interactions, IBMS had significantly higher power
      when evaluated on synthetic data. Furthermore, when applied to Alzheimer's
      disease GWA data, IBMS identified previously reported interactions. IBMS is a
      useful method for identifying variants in GWA data, and software that implements
      IBMS is freely available online from http://lbb.ut.ac.ir/Download/LBBsoft/IBMS.

PMID- 25070635
TI  - Determination of six polyynes in Oplopanax horridus and Oplopanax elatus using
      polyethylene glycol modified reversed migration microemulsion electrokinetic
      chromatography.
AB  - A PEG-modified reversed migration MEEKC method was developed for simultaneous
      determination of six polyynes, including oplopandiol, falcarindiol, oplopandiol
      acetate, (11S, 16S, 9Z)-9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate,
      oplopantriol B, and oplopantriol A, in Oplopanax horridus and Oplopanax elatus.
      The running buffer containing 0.8% v/v ethyl acetate, 3.8% w/v SDS, 6.6% v/v n
      butanol in 20 mM phosphate buffer (pH 2.5), followed by mixing with propan-2-ol
      at 30% v/v and PEG-1000 at 15% w/v, was applied in the analysis. The proposed
      method was successfully applied to determine the six polyynes in five samples of
      Oplopanax horridus and one of O. elatus. The result showed that the types and
      amounts of polyynes present were obviously different when comparing the two
      herbs. Besides, the developed PEG-modified reversed MEEKC method might be
      suitable for the analysis of hydrophobic analytes in herbal medicines.

PMID- 25070637
TI  - Phylobiochemical characterization of class-Ib aspartate/prephenate
      aminotransferases reveals evolution of the plant arogenate phenylalanine pathway.
AB  - The aromatic amino acid Phe is required for protein synthesis and serves as the
      precursor of abundant phenylpropanoid plant natural products. While Phe is
      synthesized from prephenate exclusively via a phenylpyruvate intermediate in
      model microbes, the alternative pathway via arogenate is predominant in plant Phe
      biosynthesis. However, the molecular and biochemical evolution of the plant
      arogenate pathway is currently unknown. Here, we conducted phylogenetically
      informed biochemical characterization of prephenate aminotransferases (PPA-ATs)
      that belong to class-Ib aspartate aminotransferases (AspAT Ibs) and catalyze the
      first committed step of the arogenate pathway in plants. Plant PPA-ATs and
      succeeding arogenate dehydratases (ADTs) were found to be most closely related to
      homologs from Chlorobi/Bacteroidetes bacteria. The Chlorobium tepidum PPA-AT and
      ADT homologs indeed efficiently converted prephenate and arogenate into arogenate
      and Phe, respectively. A subset of AspAT Ib enzymes exhibiting PPA-AT activity
      was further identified from both Plantae and prokaryotes and, together with site
      directed mutagenesis, showed that Thr-84 and Lys-169 play key roles in specific
      recognition of dicarboxylic keto (prephenate) and amino (aspartate) acid
      substrates. The results suggest that, along with ADT, a gene encoding prephenate
      specific PPA-AT was transferred from a Chlorobi/Bacteroidetes ancestor to a
      eukaryotic ancestor of Plantae, allowing efficient Phe and phenylpropanoid
      production via arogenate in plants today. 

PMID- 25070638
TI  - Arabidopsis and maize RidA proteins preempt reactive enamine/imine damage to
      branched-chain amino acid biosynthesis in plastids.
AB  - RidA (for Reactive Intermediate Deaminase A) proteins are ubiquitous, yet their
      function in eukaryotes is unclear. It is known that deleting Salmonella enterica
      ridA causes Ser sensitivity and that S. enterica RidA and its homologs from other
      organisms hydrolyze the enamine/imine intermediates that Thr dehydratase forms
      from Ser or Thr. In S. enterica, the Ser-derived enamine/imine inactivates a
      branched-chain aminotransferase; RidA prevents this damage. Arabidopsis thaliana
      and maize (Zea mays) have a RidA homolog that is predicted to be plastidial.
      Expression of either homolog complemented the Ser sensitivity of the S. enterica
      ridA mutant. The purified proteins hydrolyzed the enamines/imines formed by Thr
      dehydratase from Ser or Thr and protected the Arabidopsis plastidial branched
      chain aminotransferase BCAT3 from inactivation by the Ser-derived enamine/imine.
      In vitro chloroplast import assays and in vivo localization of green fluorescent
      protein fusions showed that Arabidopsis RidA and Thr dehydratase are chloroplast
      targeted. Disrupting Arabidopsis RidA reduced root growth and raised the root and
      shoot levels of the branched-chain amino acid biosynthesis intermediate 2
      oxobutanoate; Ser treatment exacerbated these effects in roots. Supplying Ile
      reversed the root growth defect. These results indicate that plastidial RidA
      proteins can preempt damage to BCAT3 and Ile biosynthesis by hydrolyzing the Ser
      derived enamine/imine product of Thr dehydratase.

PMID- 25070639
TI  - DNA topoisomerase I affects polycomb group protein-mediated epigenetic regulation
      and plant development by altering nucleosome distribution in Arabidopsis.
AB  - It has been perplexing that DNA topoisomerases, enzymes that release DNA
      supercoils, play specific roles in development. In this study, using a floral
      stem cell model in Arabidopsis thaliana, we uncovered a role for
      TOPOISOMERASE1alpha (TOP1alpha) in Polycomb Group (PcG) protein-mediated histone
      3 lysine 27 trimethylation (H3K27me3) at, and transcriptional repression of, the
      stem cell maintenance gene WUSCHEL (WUS). We demonstrated that H3K27me3
      deposition at other PcG targets also requires TOP1alpha. Intriguingly, the
      repression of some, as well as the expression of many, PcG target genes requires
      TOP1alpha. The mechanism that unifies the opposing effects of TOP1alpha appears
      to lie in its role in decreasing nucleosome density, which probably allows the
      binding of factors that either recruit PcG, as we demonstrated for AGAMOUS at the
      WUS locus, or counteract PcG-mediated regulation. Although TOP1alpha reduces
      nucleosome density at all genes, the lack of a 5' nucleosome-free region is a
      feature that distinguishes PcG targets from nontargets and may condition the
      requirement for TOP1alpha for their expression. This study uncovers a connection
      between TOP1alpha and PcG, which explains the specific developmental functions of
      TOP1alpha.

PMID- 25070640
TI  - The Arabidopsis malectin-like leucine-rich repeat receptor-like kinase IOS1
      associates with the pattern recognition receptors FLS2 and EFR and is critical
      for priming of pattern-triggered immunity.
AB  - Plasma membrane-localized pattern recognition receptors such as FLAGELLIN
      SENSING2 (FLS2) and EF-TU RECEPTOR (EFR) recognize microbe-associated molecular
      patterns (MAMPs) to activate the first layer of plant immunity termed pattern
      triggered immunity (PTI). A reverse genetics approach with genes responsive to
      the priming agent beta-aminobutyric acid (BABA) revealed IMPAIRED OOMYCETE
      SUSCEPTIBILITY1 (IOS1) as a critical PTI player. Arabidopsis thaliana ios1
      mutants were hypersusceptible to Pseudomonas syringae bacteria. Accordingly, ios1
      mutants demonstrated defective PTI responses, notably delayed upregulation of PTI
      marker genes, lower callose deposition, and mitogen-activated protein kinase
      activities upon bacterial infection or MAMP treatment. Moreover, Arabidopsis
      lines overexpressing IOS1 were more resistant to P. syringae and demonstrated a
      primed PTI response. In vitro pull-down, bimolecular fluorescence
      complementation, coimmunoprecipitation, and mass spectrometry analyses supported
      the existence of complexes between the membrane-localized IOS1 and FLS2 and EFR.
      IOS1 also associated with BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1)
      in a ligand-independent manner and positively regulated FLS2/BAK1 complex
      formation upon MAMP treatment. Finally, ios1 mutants were defective in BABA
      induced resistance and priming. This work reveals IOS1 as a regulatory protein of
      FLS2- and EFR-mediated signaling that primes PTI activation upon bacterial
      elicitation.

PMID- 25070643
TI  - Regional Groundwater Flow in the Louisville Aquifer.
AB  - The unconfined alluvial aquifer at Louisville, Kentucky, is an important source
      of water for domestic and industrial uses. It has been the object of several
      modeling studies in the past, particularly via the application of classical
      analytical solutions, and numerical solutions (finite differences and finite
      elements). A new modeling procedure of the Louisville aquifer is presented based
      on a modification of Adomian's Decomposition Method (ADM) to handle irregularly
      shaped boundaries. The new approach offers the simplicity, stability, and spatial
      continuity of analytical solutions, in addition to the ability to handle
      irregular boundaries typical of numerical solutions. It reduces to the
      application of a simple set of algebraic equations to various segments of the
      aquifer. The calculated head contours appear in reasonably agreement with those
      of previous studies, as well as with those from measured head values from the
      U.S. Geological Survey field measurement program. A statistical comparison of the
      error standard deviation is within the same range as that reported in previous
      studies that used complex numerical solutions. The present methodology could be
      easily implemented in other aquifers when preliminary results are needed, or when
      scarce hydrogeologic information is available. Advantages include a simple
      approach for preliminary groundwater modeling; an analytic description of
      hydraulic heads, gradients, fluxes, and flow rates; state variables are described
      continuously over the spatial domain; complications from stability and numerical
      roundoff are minimized; there is no need for a numerical grid or the handling of
      large sparse matrices; there is no need to use specialized groundwater software,
      because all calculations may be done with standard mathematics or spreadsheet
      programs. Nonlinearity, the effect of higher order terms, and transient
      simulations could be included if desired. 

PMID- 25070642
TI  - Transcriptome analysis reveals the same 17 S-locus F-box genes in two haplotypes
      of the self-incompatibility locus of Petunia inflata.
AB  - Petunia possesses self-incompatibility, by which pistils reject self-pollen but
      accept non-self-pollen for fertilization. Self-/non-self-recognition between
      pollen and pistil is regulated by the pistil-specific S-RNase gene and by
      multiple pollen-specific S-locus F-box (SLF) genes. To date, 10 SLF genes have
      been identified by various methods, and seven have been shown to be involved in
      pollen specificity. For a given S-haplotype, each SLF interacts with a subset of
      its non-self S-RNases, and an as yet unknown number of SLFs are thought to
      collectively mediate ubiquitination and degradation of all non-self S-RNases to
      allow cross-compatible pollination. To identify a complete suite of SLF genes of
      P. inflata, we used a de novo RNA-seq approach to analyze the pollen
      transcriptomes of S2-haplotype and S3-haplotype, as well as the leaf
      transcriptome of the S3S3 genotype. We searched for genes that fit several
      criteria established from the properties of the known SLF genes and identified
      the same seven new SLF genes in S2-haplotype and S3-haplotype, suggesting that a
      total of 17 SLF genes constitute pollen specificity in each S-haplotype. This
      finding lays the foundation for understanding how multiple SLF genes evolved and
      the biochemical basis for differential interactions between SLF proteins and S
      RNases. 

PMID- 25070644
TI  - The relationship between back pain and mortality in older adults varies with
      disability and gender: results from the Cambridge City over-75s Cohort (CC75C)
      study.
AB  - BACKGROUND: This study aims to determine whether older adults reporting back pain
      (BP) are at increased risk of premature mortality, specifically, to examine the
      association with disabling/non-disabling pain separately. METHODS: Participants
      aged >=75 years were recruited to the Cambridge City over-75s Cohort (CC75C)
      study. Participants answered interviewer-administered questions on BP and were
      followed up until death. The relationship between BP and mortality was examined
      using Cox regression, adjusted for potential confounding factors. Separate models
      were computed for men and women. RESULTS: From 1174 individuals with BP data, the
      date of death was known for 1158 (99%). A significant association was found
      between disabling BP and mortality (hazard ratio: 1.4; 95% confidence interval:
      1.1-1.8) and this remained, albeit of borderline significance, following
      adjustment for socio-demographic variables and potential disease markers (1.3;
      0.99-1.7). Further, this association was found to vary with sex: women
      experienced a 40% increase in the risk of mortality associated with disabling BP
      (1.4; 1.1-1.9), whereas no such increase was observed for men (1.0; 0.5-1.9).
      Participants with non-disabling BP were not at increased risk of mortality.
      CONCLUSIONS: This study confirmed previous findings regarding the relationship
      between pain and excess mortality. Further, we have shown that, among older
      adults, this association is specific to disabling pain and to women. Clinicians
      should be aware not only of the short-term implications of disabling BP but also
      the longer-term effects. Future research should attempt to understand the
      mechanisms underpinning this relationship to avoid excess mortality and should
      aim to determine why the relationship differs in men and women.

PMID- 25070645
TI  - The effects of age, gender, hopelessness, and exposure to violence on sleep
      disorder symptoms and daytime sleepiness among adolescents in impoverished
      neighborhoods.
AB  - Although sleep problems are associated with negative outcomes among adolescents,
      studies have not focused on sleep disorder symptoms among adolescents living in
      impoverished neighborhoods and how sleep problems may be related to two factors
      common in those environments: hopelessness and exposure to violence. This study
      used data from the longitudinal Mobile Youth Survey (MYS; N = 11,838, 49% female,
      93% African-American) to examine trajectories of sleep problems by age (10-18
      years) among impoverished adolescents as a function of gender, feelings of
      hopelessness, and exposure to violence. The results indicate that sleep problems
      associated with traumatic stress decline with age, with four notable
      distinctions. First, the steepest decline occurs during the early adolescent
      years. Second, the rate of decline is steeper for males than for females. Third,
      exposure to violence impedes the rate of decline for all adolescents, but more
      dramatically for females than for males. Fourth, the rate of decline is smallest
      for adolescents with feelings of hopelessness who also had been exposed to
      violence. To explore the generalizability of these results to other types of
      sleep disorders, we analyzed cross-sectional data collected from a subsample of
      14- and 15-year-old MYS participants (N = 263, 49% female, 100% African-American)
      who completed a sleep symptoms questionnaire. Four results from the cross
      sectional analysis extend the findings of the longitudinal analysis. First, the
      cross-sectional results showed that symptoms of apnea, insomnia, nightmares, and
      restless legs syndrome or periodic limb movement disorder (RLS/PLMD), as well as
      daytime sleepiness, increase as a function of hopelessness. Second, symptoms of
      insomnia, RLS, and nightmares, as well as daytime sleepiness, increase as
      function of exposure to violence. Third, symptoms of insomnia and RLS/PLMD are
      greater under conditions of combined hopelessness and exposure to violence than
      for either condition alone. Fourth, symptoms of RLS/PLMD are worst for females
      who have been exposed to violence and experience hopelessness. Overall, the
      findings suggest that hopelessness and exposure to violence have negative
      independent and multiplicative effects on adolescent sleep, particularly for
      females. Understanding the causal factors associated with inadequate sleep in
      impoverished adolescents is important for three reasons. First, sleep is an
      important aspect of adolescent development. Second, inadequate sleep has severe
      consequences for adolescent morbidity, mortality, and overall quality of life.
      Third, impoverished adolescents are at the most severe risk for poor outcomes,
      and improvement in their sleep may produce large gains.

PMID- 25070646
TI  - Interface engineering for high-performance top-gated MoS2 field-effect
      transistors.
AB  - Experimental evidence of the optimized interface engineering effects in MoS2
      transistors is demonstrated. The MoS2/Y2O3/HfO2 stack offers excellent interface
      control. Results show that HfO2 layer can be scaled down to 9 nm, yet achieving a
      near-ideal sub-threshold slope (65 mv/dec) and the highest saturation current
      (526 MUA/MUm) of any MoS2 transistor reported to date.

PMID- 25070647
TI  - Multifocal calcifying fibrous tumor at six sites in one patient: a case report.
AB  - Calcifying fibrous tumors (CFT) are rare benign tumors. They usually affect
      children and young adults and the incidence is equal in males and females. The
      usual clinical presentation is that of a painless mass. A computed tomography
      scan typically reveals a well-demarcated calcified lesion. CFT usually presents
      as a solitary mass and the commonest sites of occurrence are in soft tissues, the
      pleura, or the peritoneum. Multifocal occurrences at the same site have also been
      reported. The first case of CFT was reported in 1988. We present a rare case of
      multiple calcifying fibrous tumors at multiple sites in the same patient. To the
      best of our knowledge, this is the first ever reported case of multifocal CFT
      atsix different anatomical sites in one patient. 

PMID- 25070649
TI  - How will coral reef fish communities respond to climate-driven disturbances?
      Insight from landscape-scale perturbations.
AB  - Global climate change is rapidly altering disturbance regimes in many ecosystems
      including coral reefs, yet the long-term impacts of these changes on ecosystem
      structure and function are difficult to predict. A major ecosystem service
      provided by coral reefs is the provisioning of physical habitat for other
      organisms, and consequently, many of the effects of climate change on coral reefs
      will be mediated by their impacts on habitat structure. Therefore, there is an
      urgent need to understand the independent and combined effects of coral mortality
      and loss of physical habitat on reef-associated biota. Here, we use a unique
      series of events affecting the coral reefs around the Pacific island of Moorea,
      French Polynesia to differentiate between the impacts of coral mortality and the
      degradation of physical habitat on the structure of reef fish communities. We
      found that, by removing large amounts of physical habitat, a tropical cyclone had
      larger impacts on reef fish communities than an outbreak of coral-eating sea
      stars that caused widespread coral mortality but left the physical structure
      intact. In addition, the impacts of declining structural complexity on reef fish
      assemblages accelerated as structure became increasingly rare. Structure provided
      by dead coral colonies can take up to decades to erode following coral mortality,
      and, consequently, our results suggest that predictions based on short-term
      studies are likely to grossly underestimate the long-term impacts of coral
      decline on reef fish communities. 

PMID- 25070650
TI  - Experiences of apathy in people with Parkinson's disease: a qualitative
      exploration.
AB  - PURPOSE: Research has suggested that people with Parkinson's disease (PD) can
      experience apathy. This study explored the lived experiences of apathy in people
      with PD. METHOD: Seven participants with Parkinson's disease who were also
      described as having apathy were interviewed and the data analysed using
      interpretative phenomenological analysis. RESULTS: The findings were understood
      within three overlapping themes: (1) "The apathy creeps into jobs that I used to
      be able to do and no longer can do": Reduced motivation in response to the
      consequences of impairment; (2) "I hate at the end of the day if I've achieved
      nothing": The (un)acceptability of apathy; (3) "They say 'come on you lazy
      b*gger, get something done'": The social context of apathy. CONCLUSIONS: These
      themes are compared to wider research on apathy, PD and chronic illness. This
      study offers a view that, for some, apathy may be experienced as a number of
      behavioural choices influenced by increasing impairment and enacted in a social
      context. It presents an alternative conceptualisation from one describing apathy
      as the sole result of an endogenous disease process. As such, a number of
      therapeutic options are discussed but with the caveat that "apathy" need not
      always be the focus for intervention. Implications for Rehabilitation Apathy is a
      term used to denote a decrease in motivation and, although widely used, lacks
      conceptual clarity. Therefore the personal meaning of the behaviour for the
      individual within the context of their illness must be considered on assessment.
      Apathy is a societal as well as personal issue and the therapist also needs to
      assess the meaning and implications of the behaviour in the individual's social
      context. Practitioners need to be aware that apathy need not always be a focus
      for intervention. Discussion around the meaning of the behaviour may be all which
      is needed. Where individuals do wish to change their behaviours, a number of
      behavioural and psychological approaches are available. "Third wave"
      psychological therapies such as compassion- and acceptance-based approaches seem
      useful although none currently have any evidence base specifically with people
      with Parkinson's disease.

PMID- 25070648
TI  - Curcumin inhibits human retinal pigment epithelial cell proliferation.
AB  - Proliferative vitreoretinopathy (PVR) is a common cause of intraoperative failure
      following retinal reattachment surgery and is mediated in part through the
      migration, de-differentiation and proliferation of retinal pigment epithelial
      (RPE) cells. Given the cytotoxic effects of curcumin on epithelial and
      endothelial cells, in this study, we assessed the effects of curcumin on human
      RPE (hRPE) cell proliferation. WST-1 analysis revealed that curcumin
      significantly inhibited primary hRPE cell proliferation in a dose- and time
      dependent manner (P<0.001) with the greatest inhibition observed at the dose of
      15 ug/ml curcumin. Flow cytometric analysis indicated that the cytotoxic effects
      of curcumin on hRPE cell proliferation were mediated by cell cycle arrest at the
      G0/G1 phase and the induction of apoptosis (both P<0.001), which was confirmed by
      ultrastructural analysis using transmission electron microscopy. Furthermore,
      western blot analysis revealed that curcumin induced p53 and p21(WAF1/CIP1)
      expression with a concomitant decrease in proliferating cell nuclear antigen
      protein levels (P<0.05). Curcumin effectively inhibited primary hRPE cell
      proliferation, which may be mediated by the p53 pathway. Further in vivo studies
      are required in order to fully explore the therapeutic potential of curcumin for
      PVR.

PMID- 25070651
TI  - Community participation interventions for children and adolescents with a
      neurodevelopmental intellectual disability: a systematic review.
AB  - PURPOSE: The purpose of this review was to examine the effectiveness of community
      integration interventions in facilitating the community participation, self
      esteem, and quality of life of children and adolescent's with a
      neurodevelopmental intellectual disability. METHODS: Electronic searches of five
      databases and manual searches of reference lists were conducted. Community
      integration interventions which targeted friendship development, recreation
      participation, quality of life, and self-esteem were included. RESULTS: Thirteen
      studies were included in this review. A variety of study designs and
      interventions were used. All but one study reported significantly increased
      friendships, five studies reported increased recreation participation and one
      study reported increased quality of life and self-esteem. Methodological quality
      of the studies ranged from adequate to strong. CONCLUSIONS: Community integration
      interventions appear to be effective in enhancing the inclusion of children and
      adolescents with a neurodevelopmental intellectual disability. In particular,
      findings from this review highlight that there are potentially many ways to
      continue to improve the effectiveness of community participation interventions
      for this group. These include the need for the development of programmes which
      facilitate friendships alongside recreational participation, include typically
      developing peers, consider the activity preferences of children and adolescents
      in developing programmes, and accommodate individual impairments and needs
      through grading and adaptive leisure activities. Future interventions should use
      the International Classification of Functioning, Disability and Health as a
      measurement framework and consider the role of factors such as impairment,
      personal and environmental factors in facilitating community participation.

PMID- 25070653
TI  - eIF3a is over-expressed in urinary bladder cancer and influences its phenotype
      independent of translation initiation.
AB  - PURPOSE: The eukaryotic translation initiation factor (eIF) 3a, the largest
      subunit of the eIF3 complex, is a key functional entity in ribosome establishment
      and translation initiation. In the past, aberrant eIF3a expression has been
      linked to the pathology of various cancer types but, so far, its expression has
      not been investigated in transitional cell carcinomas. Here, we investigated the
      impact of eIF3 expression on urinary bladder cancer (UBC) cell characteristics
      and UBC patient survival. METHODS AND RESULTS: eIF3a expression was reduced
      through inducible knockdown in the UBC-derived cell lines RT112, T24, 5637 and
      HT1197. As a consequence of eIF3a down-regulation, UBC cell proliferation,
      clonogenic potential and motility were found to be decreased and, concordantly,
      UBC tumour cell growth rates were found to be impaired in xenotransplanted mice.
      Polysomal profiling revealed that reduced eIF3a levels increased the abundance of
      80S ribosomes, rather than impairing translation initiation. Microarray-based
      gene expression and ontology analyses revealed broad effects of eIF3a knockdown
      on the transcriptome. Analysis of eIF3a expression in primary formalin-fixed
      paraffin embedded UBC samples of 198 patients revealed that eIF3a up-regulation
      corresponds to tumour grade and that high eIF3a expression corresponds to longer
      overall survival rates of patients with low grade tumours. CONCLUSIONS: From our
      results we conclude that eIF3a expression may have a profound effect on the UBC
      phenotype and, in addition, may serve as a prognostic marker for low grade UBCs.

PMID- 25070654
TI  - Translational suppression of HIF-1alpha by miconazole through the mTOR signaling
      pathway.
AB  - BACKGROUND: Miconazole is an imidazole antifungal agent that has amply been used
      in the treatment of superficial mycosis. Preliminary data indicate that
      miconazole may also induce anticancer effects. As yet, however, little is known
      about the therapeutic efficacy of miconazole on cancer and the putative
      mechanism(s) involved. Here, we show that miconazole suppresses hypoxia inducible
      factor-1alpha (HIF-1alpha) protein translation in different cancer-derived cells.
      METHODS: The effect of miconazole on HIF-1alpha expression was examined by
      Western blotting and reverse transcriptase polymerase chain reaction assays in
      human U87MG and MCF-7 glioma and breast cancer-derived cell lines, respectively.
      The transcriptional activity of the HIF-1 complex was confirmed using a
      luciferase assay. To assess whether angiogenic factors are increased under
      hypoxic conditions in these cells, vascular endothelial growth factor (VEGF)
      levels were measured by ELISA. Metabolic labeling was performed to examine HIF
      1alpha protein translation and global protein synthesis. The role of the
      mammalian target of rapamycin (mTOR) signaling pathway was examined to determine
      translation regulation of HIF-1alpha after miconazole treatment. RESULTS:
      Miconazole was found to suppress HIF-1alpha protein expression through post
      transcriptional regulation in U87MG and MCF-7 cells. The suppressive effect of
      HIF-1alpha protein synthesis was found to be due to inhibition of mTOR.
      Miconazole significantly inhibited the transcriptional activity of the HIF-1
      complex and the expression of its target VEGF. Moreover, miconazole was found to
      suppress global protein synthesis by inducing phosphorylation of the translation
      initiation factor 2alpha (eIF2alpha). CONCLUSION: Our data indicate that
      miconazole plays a role in translational suppression of HIF-1alpha. We suggest
      that miconazole may represent a novel therapeutic option for the treatment of
      cancer.

PMID- 25070655
TI  - Effect of isolated hyperglycemia on native mechanical and biologic shoulder joint
      properties in a rat model.
AB  - Recently, diabetes has been linked to rotator cuff disease and adhesive
      capsulitis, conditions with increased stiffness and inflammation. Unfortunately,
      limited research exists examining how hyperglycemia affects the native shoulder
      (tendon and capsule) properties. Therefore, the objectives of this study were to
      compare shoulder joint mechanics, tendon properties (mechanics and
      immunohistochemistry), and capsule of healthy control and hyperglycemic rats 8
      weeks following induction of hyperglycemia with a submaximal dose of
      streptozotocin (STZ). Eighteen rats were injected with STZ to induce
      hyperglycemia or citrate buffer (control) and underwent normal cage activity for
      8 weeks. Passive joint mechanics demonstrated significantly less external
      rotation in the hyperglycemic group compared to controls, with no other group
      differences. Tendon mechanical properties (stiffness and modulus) were not
      significantly different between groups at both the insertion site and mid
      substance. Immunohistochemistry staining of the tendon and capsule demonstrated
      significantly increased interleukin 1-beta (IL1-beta) and advanced glycated end
      products (AGE) staining localized to the insertion and mid-substance of the
      tendon but not the capsule. In addition, tumor necrosis factor alpha (TNF-alpha)
      staining was significantly increased in the superior capsule but not the
      supraspinatus tendon. This study demonstrates that isolated hypergylcemia does
      not diminish shoulder mechanical properties but does induce a chronic
      inflammatory response.

PMID- 25070656
TI  - From the set-up of a screening program of breast cancer patients to the
      identification of the first BRCA mutation in the DR Congo.
AB  - BACKGROUND: Breast cancer incidence in African population is low compared to
      western countries but the mortality rate is higher and the disease presents at a
      younger age and at a more advanced stage. The World Health Organisation and the
      Breast Health Global Initiative concluded that in low and middle income countries
      early breast cancer detection can be achieved by informing women on symptoms of
      breast cancer, on the practice of breast self-examination and clinical breast
      examination by trained health care workers. Based on these recommendations, we
      set up a breast cancer awareness campaign in Kinshasa, Democratic Republic of
      Congo (DRC). This paper describes the strategy that was established and the
      results that were achieved. METHODS: A breast cancer awareness campaign was
      started in 2010 and data were collected until the end of 2012. Clinicians (expert
      group) trained nurses and health care workers (awareness groups) on clinical,
      technical and social aspects of breast cancer. Different channels were used to
      inform women about the campaign and clinical data (on medical and family history)
      were collected. The participating women were investigated with clinical breast
      examination by the awareness group. Women in whom a palpable mass was detected
      were referred to the hospital: they received a mammography and ultrasound and--in
      case of suspicious findings--additionally a core needle biopsy. In case of a
      positive family history, a blood sample was taken for genetic investigation.
      RESULTS: In total, 4,315 women participated, resulting in 1,113 radiological
      breast examinations, performed in the General Hospital of Kinshasa of which 101
      turned out to be malignant lesions. Fifty six percent of the women with breast
      cancer were less than 50 years old and 75% (65/87) were stage III tumors. A BRCA
      gene mutation was identified in a family with a severe history of breast cancer.
      CONCLUSIONS: Even without financial support, it was possible to start an
      awareness campaign for breast cancer in Kinshasa. This campaign increased the
      awareness on cancer of the women in Kinshasa. The results demonstrate that this
      campaign had an immediate impact on patients and their families.

PMID- 25070657
TI  - Biosimilar granulocyte-colony-stimulating factor for mobilization of autologous
      peripheral blood stem cells in pediatric hematology-oncology patients.
AB  - BACKGROUND: Recently biosimilars of granulocyte-colony-stimulating factor (G-CSF)
      became available for prophylaxis and treatment of postchemotherapy neutropenia
      and for mobilization of peripheral blood CD34+ cells for either autologous or
      allogeneic hematopoietic stem cell transplant. Most of the data on the
      mobilization efficacy and safety of biosimilar G-CSF are from adult patients,
      whereas no data are available in pediatric patients. STUDY DESIGN AND METHODS:
      This was a retrospective study on cases treated at three Italian pediatric
      transplant centers, from January 2011 to October 2013. Data were collected on all
      children undergoing first peripheral blood stem cell (PBSC) mobilization after
      stimulation with biosimilar G-CSF and chemotherapy. The results were compared
      with a historical control group. RESULTS: Twenty-nine children underwent
      mobilization with biosimilar G-CSF. Peak peripheral blood CD34+ cell count of 20
      * 10(6) /L was achieved in 90% of patients, with a median value of 71 * 10(6) /L.
      Eighty-three percent reached the desired target (CD34+/kg) dose. The median
      number of collected CD34+ cells was 10 * 10(6) /kg (range, 4.8 * 10(6) -68.8 *
      10(6) /kg). No difference was observed in comparison with historical control
      group mobilized with originator filgrastim. Moreover, no major and/or unexpected
      side effects were reported. CONCLUSION: Biosimilar G-CSF resulted as effective
      and safe as originator filgrastim molecule in mobilizing PBSCs in children, with
      the advantage of a reduced cost.

PMID- 25070658
TI  - MicroRNA and mRNA expression profiling in rat acute respiratory distress
      syndrome.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by
      pulmonary epithelial injury and extensive inflammation of the pulmonary
      parenchyma. Systematic analyses of microRNA (miRNA) and mRNA expression profiling
      in ARDS provide insights into understanding of molecular mechanisms of the
      pathogenesis of ARDS. The objective of this study was to identify miRNA and mRNA
      interactions in a rat model of ARDS by combining miRNA and mRNA microarray
      analyses. METHODS: Rat model of ARDS was induced by saline lavage and mechanical
      ventilation. The expression profiles of both mRNAs and miRNAs in rat ARDS model
      were performed by microarray analyses. Microarray data were further verified by
      quantitative RT-PCR. Functional annotation on dys-regulated mRNAs and miRNAs was
      carried out by bioinformatics analysis. RESULTS: The expression of 27 miRNAs and
      37 mRNAs were found to be significantly changed. The selected miRNAs and genes
      were further verified by quantitative real-time PCR. The down-regulated miRNAs
      included miR-24, miR-26a, miR-126, and Let-7a, b, c, f. The up-regulated miRNAs
      were composed of miR-344, miR-346, miR-99a, miR-127, miR-128b, miR-135b, and miR
      30a/b. Gene ontology and functional annotation analyses indicated that up
      regulated mRNAs, such as Apc, Timp1, and Sod2, were involved in the regulation of
      apoptosis. Bioinformatics analysis showed the inverse correlation of altered
      miRNAs with the expression of their predicted target mRNAs. While Sod2 was
      inversely correlated with Let-7a, b, c, f., Ebf1 and Apc were inversely
      correlated with miR-24 and miR-26a, respectively. miR-26a, miR-346, miR-135b, miR
      30a/b, miR-344, and miR-18a targeted multiple altered mRNAs. Gabrb1, Sod2,
      Eif2ak1, Fbln5, and Tspan8 were targeted by multiple altered miRNAs. CONCLUSION:
      The expressions of miRNAs and mRNAs were altered in a rat model of ARDS. The
      identified miRNA-mRNA pairs may play critical roles in the pathogenesis of ARDS.

PMID- 25070659
TI  - USP22 promotes epithelial-mesenchymal transition via the FAK pathway in
      pancreatic cancer cells.
AB  - Epithelial-mesenchymal transition (EMT) contributes to the occurrence and
      development of tumors, particularly to the promotion of tumor invasion and
      metastasis. As a newly discovered ubiquitin hydrolase family member, USP22 plays
      a key role in the malignant transformation of tumors and the regulation of the
      cell cycle. However, recent studies on USP22 have primarily focused on its role
      in cell cycle regulation, and the potential mechanism underlying the promotion of
      tumor invasion and metastasis by abnormal USP22 expression has not been reported.
      Our studies revealed that the overexpression of USP22 in PANC-1 cells promoted
      Ezrin redistribution and phosphorylation and cytoskeletal remodeling, upregulated
      expression of the transcription factors Snail and ZEB1 to promote EMT, and
      increased cellular invasion and migration. In contrast, blockade of USP22
      expression resulted in the opposite effects. In addition, the focal adhesion
      kinase (FAK) signaling pathway was shown to play a key role in the process of EMT
      induction in PANC-1 cells by USP22. Thus, the present study suggests that USP22
      acts as a regulatory protein for EMT in pancreatic cancer, which may provide a
      new approach for the targeted therapy of pancreatic cancer. 

PMID- 25070660
TI  - Oxidative stress markers and all-cause mortality at older age: a population-based
      cohort study.
AB  - BACKGROUND: The free radical/oxidative stress theory of aging has recently
      received much attention but the association of oxidative stress markers with all
      cause mortality was not yet assessed in humans. METHODS: We measured derivatives
      of reactive oxygen metabolites (d-ROM) as a proxy for the reactive oxygen species
      concentration and total thiol levels (TTL) as a proxy for the redox control
      status in 2,932 participants of a population-based cohort study from Germany.
      RESULTS: The median age of the population was 70 years and 120 (4.1%) study
      participants died during a mean follow-up of 3.3 years. Compared with the bottom
      tertiles, the top tertiles of d-ROM and TTL concentrations were both associated
      with all-cause mortality in models adjusted for age, sex, education, smoking,
      physical activity, and alcohol consumption (hazard ratios and 95% confidence
      intervals: 1.63 [1.01; 2.63] and 0.68 [0.53; 0.87], respectively). Adding
      diseases, the inflammatory marker C-reactive protein or a cumulative somatic
      morbidity index did not alter the results for TTL. However, the association of d
      ROM and mortality was attenuated and no longer statistically significant after
      adding C-reactive protein and the somatic morbidity index to the model.
      CONCLUSIONS: This study adds epidemiological evidence to the free
      radical/oxidative stress theory of aging. Both d-ROM and TTL were associated with
      mortality at older age. For TTL, this association was independent of baseline
      health status. Inflammation and higher general morbidity could be intermediate
      states on the pathway from high d-ROM levels to mortality. This hypothesis should
      to be explored by future studies with repeated measurements.

PMID- 25070661
TI  - Genetic Regulation of Female Sexual Maturation and Longevity Through Circulating
      IGF1.
AB  - We previously reported that insulin-like growth factor 1 (IGF1) was involved in
      coregulating female sexual maturation and longevity. To understand the underlying
      genetic mechanisms, based on the strain survey assays of development and aging
      traits, we crossed two mouse strains, KK/HIJ and PL/J, and produced 307 female F2
      mice. We observed the age of vaginal patency (AVP) and the life span of these
      females. We also measured circulating IGF1 level at 7, 16, 24, 52, and 76 weeks.
      IGF1 level at 7 weeks significantly correlated with AVP. IGF1 levels at ages of
      52 and 76 weeks negatively correlated with longevity (p <= .05). A gene mapping
      study found 22, 4 ,and 3 quantitative trait loci for IGF1, AVP, and life span,
      respectively. Importantly, the colocalization of IGF1, AVP, and life span
      quantitative trait loci in the distal region of chromosome 2 suggests this locus
      carries gene(s) that could regulate IGF1, AVP, and life span. In this region,
      proprotein convertase subtilisin/kexin type 2 has been found to be associated
      with female sexual maturation in a human genome-wide association study. We
      verified the roles of proprotein convertase subtilisin/kexin type 2 in regulating
      IGF1 and AVP by showing that depletion of proprotein convertase subtilisin/kexin
      type 2 significantly reduced IGF1 and delayed AVP in mice, suggesting that it
      also might be involved in the regulation of aging. 

PMID- 25070663
TI  - Progesterone inhibits endometrial cancer invasiveness by inhibiting the TGFbeta
      pathway.
AB  - Increased expression of TGFbeta isoforms in human endometrial cancer correlates
      with decreased survival and poor prognosis. Progesterone has been shown to exert
      a chemoprotective effect against endometrial cancer, and previous animal models
      have suggested that these effects are accompanied by changes in TGFbeta. The goal
      of this study was to characterize the effect of progesterone on TGFbeta signaling
      pathway components and on TGFbeta-induced protumorigenic activities in
      endometrial cancer cell lines. Progesterone significantly decreased expression of
      three TGFbeta isoforms at 72 hours after treatment except for TGFbeta2 in HEC-1B
      and TGFbeta3 in Ishikawa cells. Progesterone treatment for 120 hours attenuated
      expression of the three isoforms in all cell lines. Progesterone exposure for 72
      hours reduced expression of TGFbeta receptors in HEC-1B cells and all but
      TGFbetaR1 in Ishikawa cells. Progesterone reduced TGFbetaR3 expression in RL-95
      cells at 72 hours, but TGFbetaR1 and betaR2 expression levels were not affected
      by progesterone at any time point. SMAD2/3 and pSMAD2/3 were substantially
      reduced at 72 hours in all cell lines. SMAD4 expression was reduced in RL-95
      cells at 24 hours and in HEC-1B and Ishikawa cells at 72 hours following
      progesterone treatment. Furthermore, progesterone effectively inhibited basal and
      TGFbeta1-induced cancer cell viability and invasion, which was accompanied by
      increased E-cadherin and decreased vimentin expression. An inhibitor of TGFbetaRI
      blocked TGFbeta1-induced effects on cell viability and invasion and attenuated
      antitumor effects of progesterone. These results suggest that downregulation of
      TGFbeta signaling is a key mechanism underlying progesterone inhibition of
      endometrial cancer growth.

PMID- 25070662
TI  - Fibroblasts From Longer-Lived Species of Primates, Rodents, Bats, Carnivores, and
      Birds Resist Protein Damage.
AB  - Species differ greatly in their rates of aging. Among mammalian species life span
      ranges from 2 to over 60 years. Here, we test the hypothesis that skin-derived
      fibroblasts from long-lived species of animals differ from those of short-lived
      animals in their defenses against protein damage. In parallel studies of rodents,
      nonhuman primates, birds, and species from the Laurasiatheria superorder (bats,
      carnivores, shrews, and ungulates), we find associations between species
      longevity and resistance of proteins to oxidative stress after exposure to
      H(2)O(2) or paraquat. In addition, baseline levels of protein carbonyl appear to
      be higher in cells from shorter-lived mammals compared with longer-lived mammals.
      Thus, resistance to protein oxidation is associated with species maximal life
      span in independent clades of mammals, suggesting that this cellular property may
      be required for evolution of longevity. Evaluation of the properties of primary
      fibroblast cell lines can provide insights into the factors that regulate the
      pace of aging across species of mammals.

PMID- 25070664
TI  - Urinary PGE-M in colorectal cancer: predicting more than risk?
AB  - Progress in cancer chemoprevention has been hindered by a lack of validated
      biomarkers of risk and interventive response. The identification of accurate,
      reliable, and easily measurable risk and response biomarkers within the field of
      cancer prevention could dramatically alter our approach to the disease.
      Colorectal cancer is associated with substantial morbidity and a limited 5-year
      survival rate for late-stage disease. The identification of biomarkers to predict
      (i) those most at risk of clinically significant colorectal neoplasia in
      conjunction with or building upon current risk models and/or (ii) those most
      likely to respond to potential colorectal chemopreventive agents, such as aspirin
      and NSAIDs, would significantly advance colorectal cancer risk management.
      Urinary PGE-M is an established indicator of systemic prostaglandin E2 production
      and has previously been demonstrated to predict risk of advanced colorectal
      neoplasia in a handful of studies. In the July 2014 issue, Bezawada and
      colleagues confirmed those earlier risk associations and demonstrated that PGE-M
      can also predict responsiveness to aspirin/NSAIDs in a small subset of women
      undergoing lower endoscopy in the Nurse's Health Study. PGE-M has the potential
      to define subsets of the population that may derive greater chemopreventive
      benefit from NSAIDs, as well as the potential to optimize the use of expensive
      and/or invasive screening tests. Additional larger and more diverse prospective
      studies meeting the criteria for phase IV biomarker studies are needed to advance
      the development of PGE-M as a noninvasive biomarker of both risk and
      chemopreventive response in populations at risk for colorectal cancer.

PMID- 25070666
TI  - 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis
      and management of patients with stable ischemic heart disease: a report of the
      American College of Cardiology/American Heart Association Task Force on Practice
      Guidelines, and the American Association for Thoracic Surgery, Preventive
      Cardiovascular Nurses Association, Society for Cardiovascular Angiography and
      Interventions, and Society of Thoracic Surgeons.

PMID- 25070665
TI  - 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables
      the detection of recurrent same-site deep vein thrombosis by illuminating
      recently formed, neutrophil-rich thrombus.
AB  - BACKGROUND: Accurate detection of recurrent same-site deep vein thrombosis (DVT)
      is a challenging clinical problem. Because DVT formation and resolution are
      associated with a preponderance of inflammatory cells, we investigated whether
      noninvasive (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)
      imaging could identify inflamed, recently formed thrombi and thereby improve the
      diagnosis of recurrent DVT. METHODS AND RESULTS: We established a stasis-induced
      DVT model in murine jugular veins and also a novel model of recurrent stasis DVT
      in mice. C57BL/6 mice (n=35) underwent ligation of the jugular vein to induce
      stasis DVT. FDG-PET/computed tomography (CT) was performed at DVT time points of
      day 2, 4, 7, 14, or 2+16 (same-site recurrent DVT at day 2 overlying a primary
      DVT at day 16). Antibody-based neutrophil depletion was performed in a subset of
      mice before DVT formation and FDG-PET/CT. In a clinical study, 38 patients with
      lower extremity DVT or controls undergoing FDG-PET were analyzed. Stasis DVT
      demonstrated that the highest FDG signal occurred at day 2, followed by a time
      dependent decrease (P<0.05). Histological analyses demonstrated that thrombus
      neutrophils (P<0.01), but not macrophages, correlated with thrombus PET signal
      intensity. Neutrophil depletion decreased FDG signals in day 2 DVT in comparison
      with controls (P=0.03). Recurrent DVT demonstrated significantly higher FDG
      uptake than organized day 14 DVT (P=0.03). The FDG DVT signal in patients also
      exhibited a time-dependent decrease (P<0.01). CONCLUSIONS: Noninvasive FDG-PET/CT
      identifies neutrophil-dependent thrombus inflammation in murine DVT, and
      demonstrates a time-dependent signal decrease in both murine and clinical DVT.
      FDG-PET/CT may offer a molecular imaging strategy to accurately diagnose
      recurrent DVT.

PMID- 25070668
TI  - Association of obesity and overweight with overall survival in colorectal cancer
      patients: a meta-analysis of 29 studies.
AB  - PURPOSE: Previous studies that assessed the relationship between obesity,
      overweight, and survival in colorectal cancer (CRC) have provided conflicting
      results. Therefore, we quantitatively summarized existing evidence to estimate
      the association between obesity/overweight and overall survival (OS) in CRC
      patients and explored potentially important sources of variability. METHODS:
      Eligible studies were identified via PubMed and EMBASE searches. The summary
      hazard ratio (sHR) was estimated using a fixed-effects or random-effects model
      according to the heterogeneity between the studies. Meta-regression and subgroup
      analyses were performed to explore potential sources of heterogeneity. RESULTS: A
      total of 29 eligible studies, with 51,303 CRC patients, were finally included.
      The overall analysis showed worse OS among obese patients [sHR 1.10, 95 %
      confidence intervals (CI) 1.06-1.15], but not among overweight patients (sHR
      0.92, 95 % CI 0.86-1.00), than in normal-weight patients. Considerable
      heterogeneity was observed across studies, which was primarily attributed to the
      timing of body mass index (BMI) assessment (meta-regression p < 0.05). The
      association between obesity and worse OS was strengthened when BMI was assessed
      before diagnosis (sHR 1.30, 95 % CI, 1.17-1.44). Conversely, post-diagnostic, in
      particular post-treatment, overweight was associated with a better OS (sHR 0.79,
      95 % CI 0.70-0.91). Other factors, including gender, geographic location, and
      stage, may also modify the prognostic value of obesity or overweight.
      CONCLUSIONS: Obese but not overweight patients appear to have worse OS than
      normal-weight patients with CRC. The associations of obesity and overweight with
      OS in CRC patients majorly depend upon the timing of BMI assessment.

PMID- 25070667
TI  - Obesity and non-Hodgkin lymphoma survival in an ethnically diverse population:
      the Multiethnic Cohort study.
AB  - PURPOSE: Obesity increases mortality for several malignancies, but for non
      Hodgkin lymphoma (NHL), the association between body mass index (BMI) and
      survival is unclear. We examined the association of pre-diagnostic BMI with
      overall and NHL-specific survival in the multiethnic cohort (MEC) study of
      African Americans, Native Hawaiians, Japanese Americans, Latinos, and Caucasians.
      METHODS: MEC participants free of NHL at cohort entry and diagnosed with NHL
      during follow-up were included in the analyses (n = 1,331). BMI was based on self
      reported weight and height at cohort entry and after 6.1 years of cohort entry.
      Cox proportional hazards regression was used to calculate hazard ratios (HR) and
      95 % confidence intervals (CI) with BMI as time-varying exposure in relation to
      all-cause and NHL-specific mortality while adjusting for known confounders.
      RESULTS: The mean age at NHL diagnosis was 70.5 (range 45-89) years. After a mean
      follow-up of 4.3 +/- 3.5 years, 667 deaths including 450 NHL-specific deaths
      occurred. In multivariable models, obese patients (BMI >=30.0 kg/m(2)) had higher
      all-cause (HR 1.46, 95 % CI 1.13-1.87) and NHL-specific (HR 1.77, 95 % CI 1.30
      2.41) mortality compared with patients with high-normal BMI (22.5-24.9 kg/m(2)).
      For overweight patients (BMI = 25.0-29.9 kg/m(2)), the respective HRs were 1.21
      (95 % CI 0.99-1.49) and 1.36 (95 % CI 1.06-1.75). Cases with low-normal BMI
      (<22.5 kg/m(2)) experienced a significant 45 % higher all-cause and a 40 % higher
      NHL-specific mortality. After stratification by NHL type, the adverse effect of
      BMI was stronger for chronic lymphocytic leukemia/small lymphocytic lymphoma than
      for diffuse large B cell lymphoma and follicular lymphoma. CONCLUSIONS: Pre
      diagnostic BMI may be a suitable prognostic marker for NHL patients.

PMID- 25070669
TI  - Psoriasis and comorbidities in a southern Brazilian population: a case-control
      study.
AB  - BACKGROUND: Psoriasis is a chronic disease with worldwide prevalences of 0.6
      4.8%. Its inherent chronic inflammatory component predisposes patients to
      cardiovascular and metabolic diseases. OBJECTIVES: This study aimed to evaluate
      the associations of psoriasis with comorbidities and health risk factors such as
      smoking and alcohol intake, and to examine demographic differences in its
      occurrence in a southern Brazil population. METHODS: A case-control study was
      conducted at the Hospital de Clinicas de Porto Alegre between April 2009 and
      March 2011. The sample comprised 350 patients with psoriasis and 346 healthy
      control subjects. Data were collected using a standardized questionnaire. Tobacco
      load and alcohol consumption per person were investigated. Physical examination
      included blood pressure, waist circumference (WC), and body mass index (BMI)
      calculation. Clinical evaluation investigated whether psoriasis was localized or
      widespread and the percentage of body surface area (BSA) affected. RESULTS:
      Psoriasis patients exhibited an increased WC (P < 0.01) and BMI (P = 0.01) and
      higher incidences of smoking (P < 0.01) and depression (P < 0.01) than control
      subjects. A comparison of patients with involvement of <20% and >20% of BSA
      revealed significant differences in prevalences of hypertension (P = 0.03) and
      diabetes (P < 0.01). CONCLUSIONS: The present study demonstrated higher
      incidences of depression, increased WC, overweight, obesity, and smoking in
      psoriasis patients compared with controls. Patients with >20% of BSA affected
      were 1.69 times more likely to have hypertension and 2.9 times more likely to
      have diabetes. Healthcare providers should be alert to the increased
      cardiovascular risk and metabolic specificities of patients with psoriasis.
      Appropriate information on healthy lifestyle habits, including maintenance of a
      healthy weight and participation in physical exercise, and avoidance of alcohol
      and smoking are fundamental.

PMID- 25070670
TI  - Prenatal exposure of mice to the human liver carcinogen aflatoxin B1 reveals a
      critical window of susceptibility to genetic change.
AB  - It has become axiomatic that critical windows of susceptibility to genotoxins
      exist and that genetic damage in utero may be a trigger for later life cancers.
      Data supporting this critical window hypothesis are remarkably few. This study
      provides a quantitative bridge between DNA damage by the liver carcinogen
      aflatoxin B1 (AFB1 ) during prenatal development and the risk of later life
      genetic disease. AFB1 was given to pregnant C57BL/6J mice, carrying F1 gestation
      day 14 (GD14) embryos of the B6C3F1 genotype. Ultra-high performance liquid
      chromatography and mass spectrometry (UPLC-MS) using aflatoxin-(15) N5 -guanine
      adduct standards afforded measurement of the AFB1 -N(7) -Gua and AFB1 -FAPY
      adducts 6-hr post dosing in liver DNA of mothers and embryos. A parallel cohort
      gave birth and the livers of the F1 were analyzed for mutations in the gpt gene
      at 3 and 10 weeks of age. The data revealed mutational spectra dominated by G:C
      to T:A mutations in both the mother and offspring that are characteristic of AFB1
      and distinct from background. It was shown that adducts in GD14 embryos were 20
      fold more potent inducers of mutagenesis than adducts in parallel-dosed adults.
      This sensitivity enhancement correlated with Ki67 staining of the liver,
      reflecting the proliferative potential of the tissue. Taken together, these data
      provide insight into the relative genetic risks of prenatal and adult exposures
      to AFB1 . Early life exposure, especially during the embryonic period, is
      strikingly more mutagenic than treatment later in life. Moreover the data provide
      a baseline against which risk prevention strategies can be evaluated. 

PMID- 25070671
TI  - The impact of dosing frequency on medication adherence in chronic cardiovascular
      disease: systematic review and meta-analysis.
AB  - INTRODUCTION AND OBJECTIVE: Non-adherence to drug treatment is a major health
      problem. In Europe, it has been estimated that 9% of cardiovascular events can be
      attributed to non-adherence. The complexity of dosing regimens is one of the
      factors identified as contributing to non-adherence. In this systematic review we
      aimed to assess the impact of dosing frequency on adherence to drug treatment in
      patients with chronic cardiovascular disease. METHODS: MEDLINE and the Cochrane
      Library (November 2013) were searched for randomized controlled trials (RCTs)
      comparing different dosing regimens (once-daily administration vs. two or more
      daily administrations) and assessing adherence to therapy in patients with
      chronic cardiovascular disease. Only trials with at least five months of follow
      up were included. The results of the studies were pooled through a random effects
      meta-analysis. Relative risk (RR) and 95% confidence interval (CI) were derived.
      Statistical heterogeneity was calculated using the I(2) test. RESULTS: Four RCTs
      (a total of 2557 patients) were included. Dosing regimens with once-daily
      administration were associated with a significant 56% reduction in risk of non
      adherence to drug therapy (RR: 0.44; 95% CI: 0.35-0.54, I(2)=25%). CONCLUSIONS:
      Few clinical trials have assessed the long-term impact of dosing frequency on
      medication adherence in chronic cardiovascular disease. The best available
      evidence suggests that taking medication once daily decreases the risk of non
      adherence to treatment by approximately 50%. The impact on clinical outcomes
      remains to be established.

PMID- 25070672
TI  - Trends in use of ezetimibe after the ENHANCE trial, 2007 through 2010.
AB  - IMPORTANCE: Results from the Ezetimibe and Simvastatin in Hypercholesterolemia
      Enhances Atherosclerosis Regression (ENHANCE) trial, announced in January 2008,
      demonstrated that ezetimibe use lowered cholesterol levels but did not slow the
      progression of atherosclerosis. OBJECTIVE: To examine the association of this
      announcement with national patterns of ezetimibe prescribing, including
      medication initiation and discontinuation, as well as predictors of use. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective analysis of a national sample of adults
      18 years or older who were continuously enrolled in plans of a large US pharmacy
      benefit manager from 2007 to 2010. MAIN OUTCOMES AND MEASURES: Lipid-lowering
      therapy prescription claims were categorized as ezetimibe-containing treatments
      or any other lipid-lowering agent. Initiation was defined as an ezetimibe claim
      without another in the prior 180 days; discontinuation, as an ezetimibe claim
      without another in the subsequent 180 days. RESULTS: From 2007 to 2010, 29.1% of
      the 10,597,296 continuously eligible adults obtained at least 1 lipid-lowering
      agent prescription. Among these adults, 17.8% were prescribed ezetimibe and 95.3%
      another lipid-lowering agent, predominantly statins. Ezetimibe use peaked in
      January 2008, when 2.5% of all adults were ezetimibe users, but declined to 1.8%
      by December 2010. The ENHANCE trial announcement was associated with a
      nonsignificant 0.16% fewer monthly ezetimibe users (P = .11) but a significant
      0.14% more monthly monotherapy users and 0.30% fewer users of ezetimibe
      concomitant with other lipid-lowering agents (both P = .01). The ENHANCE trial
      was also associated with 0.44% fewer monthly ezetimibe initiations (P = .002) and
      10.4% more monthly ezetimibe discontinuations (P < .001), particularly of
      ezetimibe monotherapy for both. More than half of adults who initiated ezetimibe
      use did so without first being prescribed another lipid-lowering agent, both
      before (50%-60%) and after (60%-70%) the trial. Those aged 50 to 64 years and
      those living in the East South Central US Census division were both more likely
      to initiate and less likely to discontinue ezetimibe after the ENHANCE trial.
      CONCLUSIONS AND RELEVANCE: After announcement of the results of the ENHANCE
      trial, nearly 2% of all continuously enrolled adult beneficiaries within a large
      US pharmacy benefit manager used ezetimibe, although ezetimibe initiations
      declined and discontinuations increased.

PMID- 25070673
TI  - Adolescents and the internet: what mental health clinicians need to know.
AB  - The Internet's permeation into daily life has profoundly changed the practice of
      psychiatry with adolescents, who mobilize online social media and related
      technologies in their efforts to develop identity and "hang out" with peers.
      Technology offers both challenges and opportunities to mental health
      professionals working with teens. Practitioners will need a new skill-set,
      including keeping abreast of technological developments; professionally
      incorporating technology into clinical assessment and practice; identifying the
      negative impacts of technology on teens' physical and mental health and the
      particular vulnerabilities of at-risk patients in a digital world; and guiding
      patients and parents about interventions. Particular patient factors related to
      race/ethnicity, gender and sexual orientation, mental health and trauma history,
      family culture, parenting style, and personality traits will need to be
      considered. This article provides an overview of the literature on adolescents
      and the Internet focusing on recent research on Internet and digital technologies
      used for social communication among youth. 

PMID- 25070674
TI  - JC virus antibody status in a pediatric multiple sclerosis cohort: prevalence,
      conversion rate and influence on disease severity.
AB  - BACKGROUND: Because of the emergence of novel therapies for multiple sclerosis
      (MS) and the associated increased risk of progressive multifocal
      leukoencephalopathy, John Cunningham (JC) virus infection has become a focus of
      interest for neurologists. However, little is known about JC virus infection in
      pediatric MS to date. OBJECTIVE: We aimed to analyze the prevalence of anti-JC
      virus antibodies, the conversion rate and the influence of the anti-JC virus
      antibody status on the clinical course in a large pediatric MS cohort. METHODS:
      Anti-JC virus antibodies were analyzed in serum samples within six months of
      disease onset and during the course of the disease. Clinical data were extracted
      from a pediatric MS databank. RESULTS: A total of 51.6% of 256 patients were
      found to be positive for anti-JC virus antibodies at onset of disease. No
      correlation between antibody status and clinical course was seen. Analyzing 693
      follow-up serum samples revealed high titer stability, and an annual conversion
      rate of 4.37% was seen. CONCLUSION: No evidence was found that seropositivity for
      anti-JC virus antibodies influences the clinical course. Surprisingly,
      seroprevalence for anti-JC virus antibodies was more than twice as high as
      anticipated in this age group, raising the question of whether the infection
      increases the risk of MS development.

PMID- 25070675
TI  - Digesting the emerging role for the gut microbiome in central nervous system
      demyelination.
AB  - The fields of microbiology, immunology, neurology and nutrition are rapidly
      converging, as advanced sequencing and genomics-based methodologies have enabled
      the mapping out of the microbial diversity of humans for the first time. Bugs,
      guts, brains and behavior were once believed to be separate domains of clinical
      practice and research; however, recent observations in our understanding of the
      microbiome indicate that the boundaries between domains are becoming permeable.
      This permeability is multidirectional: Biological systems are operating
      simultaneously in a vastly complex and interconnected web. Understanding the
      microbiome-gut-brain axis will entail fleshing out the mechanisms by which
      transduction across each domain occurs, allowing us ultimately to appreciate the
      role of commensal organisms in shaping and modulating host immunity. This article
      will highlight animal and human research to date, as well as highlight directions
      for future research. We speculate that the gut microbiome is potentially the
      premier environmental risk factor mediating inflammatory central nervous system
      demyelination, in particular multiple sclerosis. 

PMID- 25070676
TI  - Progression rates and sample size estimates for PPMS based on the CLIMB study
      population.
AB  - BACKGROUND: The clinical trial design for primary progressive multiple sclerosis
      (PPMS) requires understanding of disability progression in modern patient
      cohorts. OBJECTIVE: The objective of this paper is to characterize demographic
      and clinical characteristics of PPMS and assess rate of disability progression.
      METHODS: We studied PPMS (n = 73) and relapsing-onset MS (ROMS) patients (n =
      1541) enrolled in CLIMB, a longitudinal study of MS patients at the Brigham and
      Women's Hospital (Boston, MA). Disability progression for each group was compared
      using interval-censored survival analysis and time to six-month sustained
      progression. RESULTS: The PP group had a 1.09:1 male:female ratio compared to
      1:2.89 for the RO group and greater mean age of onset (PP: 44.4+/-9.6; RO: 32.7+/
      9.9; p < 0.0001). Motor symptoms at onset and first symptoms localized to spinal
      cord were each strongly associated with PPMS (p < 0.001). Median time from onset
      to EDSS 6.0 was faster in PPMS (p < 0.001). PPMS patients progressed faster to
      EDSS 3 (p < 0.001) and from EDSS 3 to 6 (p < 0.001). Median time to sustained
      progression in the PP group was 4.85 years (95% CI 2.83-8.35), significantly
      faster than the RO group (p < 0.001). CONCLUSIONS: Our modern PPMS cohort is
      demographically similar to previously studied cohorts. PPMS is associated with
      faster disability accrual than ROMS. Current real-world observations of time to
      sustained progression will inform design of new clinical trials for PPMS.

PMID- 25070677
TI  - Left atrial myxoma presenting with white matter lesions suggestive of multiple
      sclerosis: the differential diagnosis goes beyond MRI.

PMID- 25070678
TI  - Disclosure of disease status among employed multiple sclerosis patients:
      association with negative work events and accommodations.
AB  - BACKGROUND: Unemployment is common in multiple sclerosis (MS) and detrimental to
      quality of life. Studies suggest disclosure of diagnosis is an adaptive strategy
      for patients. However, the role of cognitive deficits and psychiatric symptoms in
      disclosure are not well studied. OBJECTIVE: The goals of this paper were to (a)
      determine clinical factors most predictive of disclosure, and (b) measure the
      effects of disclosure on workplace problems and accommodations in employed
      patients. METHODS: We studied two overlapping cohorts: a cross-sectional sample
      (n = 143) to determine outcomes associated with disclosure, and a longitudinal
      sample (n = 103) compared at four time points over one year on reported problems
      and accommodations. A case study of six patients, disclosing during monitoring,
      was also included. RESULTS: Disclosure was associated with greater physical
      disability but not cognitive impairment. Logistic regression predicting
      disclosure status retained physical disability, accommodations and years of
      employment (p < 0.0001). Disclosed patients reported more work problems and
      accommodations over time. The case study revealed that reasons for disclosing are
      multifaceted, including connection to employer, decreased mobility and problems
      at work. CONCLUSION: Although cognitive impairment is linked to unemployment, it
      does not appear to inform disclosure decisions. Early disclosure may help
      maintain employment if followed by appropriate accommodations.

PMID- 25070679
TI  - Anisotropic zero-index waveguide with arbitrary shapes.
AB  - We design a series of waveguides composed of uniform anisotropic epsilon-near
      zero media. Unlike normal waveguides in which the transmission rate strongly
      depends on the width and the boundary shape, such waveguides can achieve high
      transmission with almost arbitrary width and boundary shapes, leading to
      applications such as unusual waveguides, wave expanders and compressors,
      splitters, bends, and devices with combined purposes. The physical origin of such
      high transmission can be explained by using transformation optics and the
      condition for total transmission is derived. Numerical simulations with
      multilayers consisting of dielectric and negative-permittivity materials proved
      our theory. Our work provides a unified physical picture for waveguide structures
      based on anisotropic epsilon-near-zero media. 

PMID- 25070680
TI  - Comprehensive biomarker testing of glycemia, insulin resistance, and beta cell
      function has greater sensitivity to detect diabetes risk than fasting glucose and
      HbA1c and is associated with improved glycemic control in clinical practice.
AB  - Blood-based biomarker testing of insulin resistance (IR) and beta cell
      dysfunction may identify diabetes risk earlier than current glycemia-based
      approaches. This retrospective cohort study assessed 1,687 US patients at risk
      for cardiovascular disease (CVD) under routine clinical care with a comprehensive
      panel of 19 biomarkers and derived factors related to IR, beta cell function, and
      glycemic control. The mean age was 53 +/- 15, 42 % were male, and 25 % had
      glycemic indicators consistent with prediabetes. An additional 45 % of the
      patients who had normal glycemic indicators were identified with IR or beta cell
      abnormalities. After 5.3 months of median follow-up, significantly more patients
      had improved than worsened their glycemic status in the prediabetic category (35
      vs. 9 %; P < 0.0001) and in the "high normal" category (HbA1c values of 5.5-5.6;
      56 vs. 18 %, p < 0.0001). Biomarker testing can identify IR early, enable and
      inform treatment, and improve glycemic control in a high proportion of patients. 

PMID- 25070681
TI  - Rapid recovery of baroreceptor reflexes in acute myocardial infarction is a
      marker of effective tissue reperfusion.
AB  - Baroreflex sensitivity (BRS) measured several days after myocardial infarction
      (MI) is a powerful predictor of cardiovascular mortality. No information is
      available on BRS in the early hours of MI. The possibility to reliably assess BRS
      in the acute phase of MI and its clinical correlates were evaluated in 45
      patients treated with primary percutaneous coronary intervention (pPCI). BRS
      (sequence method) was assessed 1, 3, 6, and 12 h after PCI. ST resolution (STRes)
      was considered present if ST had decreased >=70 % 3 h after PCI. BRS was 10.7 +/-
      6.2 1 h after PCI; at 12 h it was 15.4 +/- 5.2 and 8.4 +/- 4.8 ms/mmHg in
      patients with and without STRes, respectively (p < 0.001). STRes was an
      independent predictor of 12 h BRS (p = 0.005) and of 1-12 h BRS difference (p =
      0.002). BRS can be reliably assessed in the first hours of MI; it shows a rapid
      recovery in patients with STRes and a significant depression in patients without
      STres. 

PMID- 25070682
TI  - The electronic health record for translational research.
AB  - With growing adoption and use, the electronic health record (EHR) represents a
      rich source of clinical data that also offers many benefits for secondary use in
      biomedical research. Such benefits include access to a more comprehensive medical
      history, cost reductions, and increased efficiency in conducting research, as
      well as opportunities to evaluate new and expanded populations for sufficient
      statistical power. Existing work utilizing EHR data has uncovered some
      complexities and considerations for their use but, more importantly, has also
      generated practical lessons and solutions. Given an understanding of EHR data use
      in cardiovascular research, expanded adoption of this data source offers great
      potential to further transform the research landscape. 

PMID- 25070683
TI  - Correlation between comprehensive evaluation of coronary artery lesion severity
      and long-term clinical outcomes in Chinese octogenarians with acute coronary
      syndrome.
AB  - BACKGROUND: There is little known about long-term outcome data regarding acute
      coronary syndrome (ACS) in Chinese octogenarians (> 80 years old). Long-term
      outcomes of octogenarians with ACS may be associated with increased complicated
      coronary artery lesion severity. METHODS: We classified 536 consecutive
      octogenarians with ACS into four groups based on Gensini score. Survival and
      major adverse cardiac event (MACE) rates were calculated using the Kaplan-Meier
      method. Multivariate Cox regression was used to identify mortality predictors.
      The follow-up period was 27 (IQR15-36) months. RESULTS: The overall long-term
      mortality rate was 9.1% and increased from 3.0% in group 1 to 16.7% in group 4.
      Increasing coronary artery lesion severity was associated with increased long
      term mortality and MACE rates. ROC curve analysis showed that the predictive cut
      off value of Gensini score for mortality was 53. Gensini score provided
      significant reclassification of mortality (net reclassification index 0.195,
      P<0.01). Age, gender, heart rate, SBP, chronic renal failure, e-GFR, GRACE score,
      Gensini score, and ACS type were different between surviving and deceased
      patients. Notably, chronic renal failure (OR=2.55, P=0.036), GRACE score
      (OR=1.10, P=0.006), and Gensini score(OR=1.11, P=0.003) were the independent
      predictors of long-term mortality. CONCLUSIONS: Long-term mortality of
      octogenarians with ACS was associated with increased comprehensive coronary
      artery lesion severity. Gensini score was an effective parameter for evaluation
      of long-term mortality.

PMID- 25070684
TI  - The rapidly evolving use of extracorporeal life support (ECLS) in adults.

PMID- 25070685
TI  - 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in
      neuroendocrine tumours refractory to beta radiation: a first-in-human experience.
AB  - PURPOSE: Radiopeptide therapy using a somatostatin analogue labelled with a beta
      emitter such as (90)Y/(177)Lu-DOTATOC is a new therapeutic option in
      neuroendocrine cancer. Alternative treatments for patients with refractory
      disease are rare. Here we report the first-in-human experience with (213)Bi
      DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters.
      METHODS: Seven patients with progressive advanced neuroendocrine liver metastases
      refractory to treatment with (90)Y/(177)Lu-DOTATOC were treated with an
      intraarterial infusion of (213)Bi-DOTATOC, and one patient with bone marrow
      carcinosis was treated with a systemic infusion of (213)Bi-DOTATOC.
      Haematological, kidney and endocrine toxicities were assessed according to CTCAE
      criteria. Radiological response was assessed with contrast-enhanced MRI and
      (68)Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven
      patients. RESULTS: The biodistribution of (213)Bi-DOTATOC was evaluable with 440
      keV gamma emission scans, and demonstrated specific tumour binding. Enduring
      responses were observed in all treated patients. Chronic kidney toxicity was
      moderate. Acute haematotoxicity was even less pronounced than with the preceding
      beta therapies. CONCLUSION: TAT can induce remission of tumours refractory to
      beta radiation with favourable acute and mid-term toxicity at therapeutic
      effective doses.

PMID- 25070686
TI  - (177)Lu-EDTMP for palliation of pain from bone metastases in patients with
      prostate and breast cancer: a phase II study.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy and safety of
      (177)Lu-EDTMP for pain palliation in patients with bone metastases from
      castration-resistant prostate and breast cancer. The secondary objective was to
      compare low-dose and high-dose (177)Lu-EDTMP in bone pain palliation. METHODS:
      Included in the study were 44 patients with documented breast carcinoma (12
      patients; age 47 +/- 13 years) or castration-resistant prostate carcinoma (32
      patients; age 66 +/- 9 years) and skeletal metastases. Patients were randomized
      into two equal groups treated with (177)Lu-EDTMP intravenously at a dose of 1,295
      MBq (group A) or 2,590 MBq (group B). Pain palliation was evaluated using a
      visual analogue score (VAS), analgesic score (AS) and Karnofsky performance score
      (KPS) up to 16 weeks. Toxicity was assessed in terms of haematological and renal
      parameters. RESULTS: The overall response rate (in all 44 patients) was 86 %.
      Complete, partial and minimal responses were seen in 6 patients (13 %), 21
      patients (48 %) and 11 patients (25 %), respectively. A favourable response was
      seen in 27 patients (84 %) with prostate cancer and in 11 patients (92 %) with
      breast cancer. There was a progressive decrease in the VAS from baseline up to 4
      weeks (p < 0.05). Also, AS decreased significantly from 1.8 +/- 0.7 to 1.2 +/-
      0.9 (p < 0.0001). There was an improvement in quality of life of the patients as
      reflected by an increase in mean KPS from 56 +/- 5 to 75 +/- 7 (p < 0.0001). The
      overall response rate in group A was 77 % compared to 95 % in group B (p =
      0.188). There was a significant decrease in VAS and AS accompanied by an increase
      in KPS in both groups. Nonserious haematological toxicity (grade I/II) was
      observed in 15 patients (34 %) and serious toxicity (grade III/IV) occurred in 10
      patients (23 %). There was no statistically significant difference in
      haematological toxicity between the groups. CONCLUSION: (177)Lu-EDTMP was found
      to be a safe and effective radiopharmaceutical for bone pain palliation in
      patients with metastatic prostate and breast carcinoma. There were no differences
      in efficacy or toxicity between patients receiving low-dose and high-dose (177)Lu
      EDTMP.

PMID- 25070687
TI  - Efficacy and safety of conversion from cyclosporine to everolimus in living-donor
      kidney transplant recipients: an analysis from the ZEUS study.
AB  - Conversion of living-donor kidney transplant patients from calcineurin inhibitor
      therapy to an mTOR inhibitor is poorly documented. In the prospective,
      multicentre ZEUS study, 300 kidney transplant recipients without prior rejection
      (Banff grade >1) and serum creatinine <=265 MUmol/l were randomized to continue
      cyclosporine or convert to everolimus at 4.5 months post-transplant. In a post
      hoc analysis of 80 living-donor recipients, adjusted estimated GFR (Nankivell) at
      month 12 (the primary endpoint) was 74.3 (95% CI [70.7, 77.9]) ml/min/1.73 m(2)
      with everolimus versus 63.8 (95% CI [60.0, 67.7]) ml/min/1.73 m(2) ) with
      cyclosporine, a difference of 10.5 ml/min/1.73 m(2) in favour of everolimus (P <
      0.001). From randomization to month 12, adjusted estimated GFR increased by a
      mean of 9.8 (95% CI [6.2, 13.4]) ml/min/1.73 m(2) with everolimus versus -0.7
      (95% CI [-4.6, 3.1]) ml/min/1.73 m(2) ) (P < 0.001) with cyclosporine. There were
      six biopsy-proven acute rejection episodes in everolimus-treated patients (five
      Banff grade I) and one episode in cyclosporine-treated patients (Banff grade 1).
      Overall safety profile was similar between groups. Discontinuation due to adverse
      events occurred in three everolimus patients (7.1%) and five cyclosporine
      patients (13.2%) between randomization and month 12. Initiation of everolimus
      with early elimination of calcineurin therapy is associated with a significant
      renal benefit at 12 months post-transplant that is observed in both living and
      deceased-donor recipients. (clinicaltrials.gov NCT00154310). 

PMID- 25070688
TI  - Genetic mapping and QTL analysis of growth traits in the large yellow croaker
      Larimichthys crocea.
AB  - Large yellow croaker (Larimichthys crocea) is an important maricultured species
      in China. A genetic linkage map of the large yellow croaker was constructed using
      type II microsatellites and expressed sequence tag (EST)-derived microsatellites
      in two half-sib families (two females and one male). A total of 289
      microsatellite markers (contained 93 EST-SSRs) were integrated into 24 linkage
      groups, which agreed with the haploid chromosome number. The map spanned a length
      of 1,430.8 cm with an average interval of 5.4 cm, covering 83.9 % of the
      estimated genome size (1,704.8 cm). A total of seven quantitative trait locis
      (QTLs) were detected for growth traits on five linkage groups, including two 1 %
      and five 5 % chromosome-wide significant QTLs, and explained from 2.33 to 5.31 %
      of the trait variation. The identified QTLs can be applied in marker-assisted
      selection programs to improve the growth traits. 

PMID- 25070689
TI  - Perioperative outcomes of primary renal tumour resections: comparison of in-hours
      to out-of-hours surgery.
AB  - PURPOSE: Primary resection is typically performed for children with localised
      suspected Wilms tumours. Resource limitation may necessitate performing these
      operations nights and weekends. We hypothesise that outcomes will be worse in
      patients having nephrectomies out-of-hours (OOH) compared to those in-hours (IH).
      METHODS: With IRB ethics approval, primary renal tumour resections performed on
      oncology patients from 1989-2011 were reviewed retrospectively. IH operations
      were defined as Monday-Friday 0745-1530 hours. Outcomes included major
      intraoperative complications, capsule rupture, and blood loss. Data were analysed
      using Fischer Exact and Mann-Whitney U tests. RESULTS: There were 64 patients
      with renal tumours who underwent primary resection. Forty-five procedures were
      performed IH, and 19 OOH. Groups were similar in age, ASA status, tumour size and
      grade. In a comparison of major intraoperative complications, capsule rupture,
      and mean blood loss, differences were 2 vs. 26% (p = 0.007), 27 vs. 42% (p =
      0.12), 178 vs. 244 ml (p = 0.15) for IH and OOH respectively. There was one
      perioperative mortality (OOH). CONCLUSIONS: Primary renal tumour resections
      performed OOH were associated with an increase in major complications compared to
      those performed in standard hours. Avoidance of OOH operating where possible may
      reduce morbidity for children undergoing primary renal tumour resections.

PMID- 25070690
TI  - Surgical reconstruction and endoscopic pancreatic stent for traumatic pancreatic
      duct disruption.
AB  - Nonoperative management is acceptable treatment for minor pancreatic injuries.
      However, management of major pancreatic duct injury in children remains
      controversial. We present our experience in treating isolated pancreatic duct
      injury. We describe the cases of three male patients treated for complete
      pancreatic duct disruption in the past 5 years at our institution. We performed
      pancreatic duct repair to avoid distal pancreatectomy and to maintain normal
      pancreatic function. All patients underwent enhanced computed tomography and
      endoscopic retrograde cholangiopancreatography in the early period. The injuries
      were classified as grade III according to the American Association for the
      Surgery of Trauma classification. In two cases, we performed end-to-end
      anastomosis of the pancreatic duct during the delayed period. In the third case,
      we placed a stent across the disruption to the distal pancreatic duct. The
      patients' postoperative courses were uneventful, and the average hospitalization
      was 25.6 days after the procedure. At a median follow-up of 36 months (range 14
      54 months), all patients remain asymptomatic, with normal pancreatic function,
      but with persistent distal pancreatic duct dilatation. We suggest that distal
      pancreatectomy should not be routinely performed in patients with isolated
      pancreatic duct injury.

PMID- 25070691
TI  - Reduced efficacy of ivermectin treatments in gastrointestinal nematode infections
      of grazing cattle in Japan.
AB  - Fecal egg count reduction tests (FECRT) and larval migration inhibition tests
      (LMIT) were conducted to assess the efficacy of ivermectin (IVM) against
      gastrointestinal nematodes on 2 cattle farms in northern Japan in 2009 and 2010.
      Twelve to 20 calves on each farm were treated topically with 0.5 mg IVM/kg 2
      (Farm 2) or 4 times (Farm 1) during the grazing season (May-October). On Farm 1,
      fecal egg count (FEC) reduction at 14 days post-treatment ranged from 16 to 87%
      in 2009 and from 24 to 96% in 2010, with relatively low reductions in August and
      October (16-53%). Conversely, IVM treatment on Farm 2 reduced FEC by 97% in
      September 2009. Larvae obtained from fecal cultures and identified by PCR-RFLP
      analysis revealed that the dominant species on both farms prior to IVM
      administration was Cooperia oncophora. In 2009, the FEC reduction of C. oncophora
      on Farm 1 decreased from 85% in May to 56% in August. In 2010, the reduction in
      C. oncophora in August was 28%. In the LMIT using larvae collected from the fecal
      cultures on Farm 1 in May and August 2009, the EC50 value of IVM in C. oncophora
      in August (0.892 ug/ml) was 3 times higher than that in May (0.296 ug/ml). The
      results of the LMIT corroborated the FECRT data, indicating the presence of IVM
      resistant C. oncophora on Farm 1, at least in August. This is the first report of
      IVM-resistant nematodes in Japanese cattle. 

PMID- 25070693
TI  - Sexual activity among Malaysian school-going adolescents: what are the risk and
      protective factors?
AB  - This study aimed to identify risk and protective factors associated with sexual
      activity among Malaysian adolescents. Data from the World Health Organization
      Global School-based Student Health Survey 2012 were analyzed. A total of 23 645
      students aged 12 to 17 years responded using self-administered validated
      questionnaire. The overall prevalence of reported ever-had sex was 8.3%. Logistic
      regression analysis revealed that ever-had sex was positively significantly
      associated with ever-used drugs (adjusted odds ratio [aOR] = 7.71; 95% confidence
      interval [CI] = 6.51-9.13), and to a lesser extent, ever-smoked (aOR = 1.83; 95%
      CI = 1.62-2.07) and ever-consumed alcohol (aOR = 1.33; 95% CI = 1.15-2.53).
      Protective factors against ever-had sex were having a close friend (aOR = 0.63;
      95% CI = 0.50-0.81), parental bonding (aOR = 0.72; 95% CI = 0.65-0.81),
      supportive peers (aOR = 0.77; 95% CI = 0.69-0.86), and parental connectedness
      (aOR = 0.88; 95% CI = 0.78-0.99). Although the prevalence of sexual activity
      among school-going adolescents in Malaysia is relatively low, identifying the
      risk and protective factors is crucial toward developing an integrated multiple
      approach to preventing sexual-related problems. 

PMID- 25070692
TI  - Feasibility of a GP delivered skin cancer prevention intervention in Australia.
AB  - BACKGROUND: Despite years of public education, sun-related behaviours are
      difficult to change and a recent survey showed low levels of sun protection. In
      this study we evaluated the feasibility and acceptability of an opportunistic
      skin cancer prevention intervention in general practice. METHODS: We used a
      controlled pre-and-post intervention design. Participants (n = 100) were
      recruited sequentially from patients attending two general practices in Sydney,
      Australia, from November to December 2010. Participants in the intervention
      practice (n = 50) received general practitioner delivered sun protection advice
      after completing a skin cancer risk assessment tool, and a sun protection
      pamphlet, in addition to routine care, at a single attendance. The skin cancer
      risk assessment tool provided three levels of risk. The general practitioner (GP)
      reinforced the level of risk and discussed sun protection. Participants in the
      control practice (n = 50) received routine care. We measured feasibility by
      patients' and GPs' participation in the intervention and time taken, and
      acceptability by intervention participants and GPs ratings of the intervention.
      We measured reported sun-related knowledge, attitudes and behaviour between the
      two groups at 1 and 13 months. RESULTS: The intervention was found to be feasible
      within existing primary care team arrangements. Participation at baseline was 81%
      (108/134), and repeated participation was 88% (88/100) at 1 month and 70%
      (70/100) at 13 months. Participants and practitioners found the intervention
      acceptable. At 1 month, sun-related knowledge had increased in both patient
      groups, with a greater increase in the intervention group (adjusted mean
      difference 0.48, p = 0.034). There were no differences between groups in sun
      related knowledge, attitudes and behaviour at 13 months. CONCLUSIONS: A brief
      opportunistic skin cancer prevention intervention in general practice is feasible
      and acceptable. Further research in this setting with a more intensive
      intervention would be justified.

PMID- 25070694
TI  - Determinants of dietary supplements use among adolescents in Malaysia.
AB  - Dietary supplements use is relatively widespread in some countries but knowledge
      of supplements consumption in Malaysia is limited, more so among adolescents.
      This study aimed to investigate the determinants of dietary supplements use among
      Malaysian adolescents using multiple logistic regressions analysis. Data from the
      Malaysia School-based Nutrition Survey 2012 based on a 2-stage stratified
      sampling was used. The prevalence of vitamin/mineral supplements and food
      supplements intake among adolescents was 54.1% and 40.2%, respectively. Usage was
      significantly higher among younger adolescents and among boys. Dietary
      supplements were also taken mostly by those who thought they were underweight.
      The most common vitamin/mineral supplements and food supplements consumed were
      vitamin C and bee products. The main reason for taking supplements was parents'
      instruction. These findings can be useful for developing health communications on
      supplement use targeted to adolescents and their parents. 

PMID- 25070695
TI  - Self-perception of body weight status and weight control practices among
      adolescents in Malaysia.
AB  - The prevalence of overweight and obesity among adolescents is rising rapidly in
      many countries, including Malaysia. This article aims to present the associations
      between body mass index-based body weight status, body weight perception, and
      weight control practices among adolescents in Malaysia. The Malaysia School Based
      Nutrition Survey 2012, which included a body weight perception questionnaire and
      anthropometric measurements, was conducted on a representative sample of 40 011
      students from Standard 4 until Form 5, with a 90.5% response rate. Comparing
      actual and perceived body weight status, the findings show that 13.8% of
      adolescents underestimated their weight, 35.0% overestimated, and 51.2% correctly
      judged their own weight. Significantly more normal weight girls felt they were
      overweight, whereas significantly more overweight boys perceived themselves as
      underweight. The overall appropriateness of weight control practices to body
      weight was 72.6%. Adolescents attempting to lose or gain weight need to have
      better understanding toward desirable behavioral changes. 

PMID- 25070696
TI  - Factors associated with physical inactivity among school-going adolescents: data
      from the Malaysian School-Based Nutrition Survey 2012.
AB  - The importance of physical activity to health is well recognized. Good health
      habits should begin from a young age. This article aims to explore physical
      activity among Malaysian school adolescents and factors associated with it. Data
      from the Malaysian School-Based Nutrition Survey (MSNS), comprising a nationally
      representative sample of school-going children aged 10 to 17 years, were used.
      The overall prevalence of physically inactive adolescents was 57.3%. Age in years
      (adjusted odds ratio = 1.2; 95% confidence interval = 1.16-1.23), gender -
      females (adjusted odds ratio = 2.9; 95% confidence interval = 2.66-3.10),
      afternoon school session, breakfast consumption (no breakfast and irregular
      breakfast), body mass index status (obese and underweight), and body weight
      perception (underweight perceivers) were significant factors associated with
      physical inactivity among Malaysian adolescents. Thus, there is evidence that
      programs to promote physical activity in this group should consider the
      combination of the aforementioned factors at the household, school, and community
      levels.

PMID- 25070697
TI  - Prevalence and correlates of depression among adolescents in Malaysia.
AB  - Depression among adolescents has been recognized as a major public health issue.
      The objective of this study was to determine the prevalence and correlates of
      depression among school-going adolescents in Malaysia. Data from the Malaysia
      Global School-based Health Survey (GSHS) 2012 were analyzed with additional data
      from the validated DASS21 (Depression, Anxiety, and Stress) questionnaire. The
      study revealed that 17.7% of respondents had depressive symptoms. Multivariate
      analysis further showed that feeling lonely (adjusted odds ratio [aOR] = 2.99;
      95% CI = 2.57-3.47), Indian ethnicity (aOR = 2.00; 95% CI = 1.63-2.44), using
      drugs (aOR = 1.85; 95% CI = 1.21-2.82), and being bullied (aOR = 1.79; 95% CI =
      1.60-1.99) were significantly associated with depressive symptoms. Lack of
      parental supervision, alcohol use, and tobacco use were also significant risk
      factors. Addressing depressive symptoms among adolescents may have implications
      for managing their risks of being bullied and substance use. This study also
      highlights the need to further investigate depressive symptoms among adolescents
      of Indian ethnicity. 

PMID- 25070698
TI  - Gold nanorods with sub-nanometer separation using cucurbit[n]uril for SERS
      applications.
AB  - The capability of cucurbit[n]uril to align gold nanorods, leading to optical
      coupling into the infrared region, is shown. Cryo-TEM and tomographic imaging
      confirm the presence of aligned Au nanorods. Full electromagnetic simulations,
      which support the observed plasmonic modes and predict large enhancements in the
      inter-particle junction, are performed. This construct is then further utilized
      for surface enhanced Raman spectroscopy. 

PMID- 25070699
TI  - Distribution of coronoid fracture lines by specific patterns of traumatic elbow
      instability.
AB  - PURPOSE: To determine if specific coronoid fractures relate to specific overall
      traumatic elbow instability injury patterns and to depict any relationship on
      fracture maps and heat maps. METHODS: We collected 110 computed tomography (CT)
      studies from patients with coronoid fractures. Fracture types and pattern of
      injury were characterized based on anteroposterior and lateral radiographs, 2-
      and 3-dimensional CT scans, and intraoperative findings as described in operative
      reports. Using quantitative 3-dimensional CT techniques we were able to
      reconstruct the coronoid and reduce fracture fragments. Based on these
      reconstructions, fracture lines were identified and graphically superimposed onto
      a standard template in order to create 2-dimensional fracture maps. To further
      emphasize the fracture maps, the initial diagrams were converted into fracture
      heat maps following arbitrary units of measure. The Fisher exact test was used to
      evaluate the association between coronoid fracture types and elbow fracture
      dislocation patterns. RESULTS: Forty-seven coronoid fractures were associated
      with a terrible triad fracture dislocation, 30 with a varus posteromedial
      rotational injury, 1 with a anterior olecranon fracture dislocation, 22 with a
      posterior olecranon fracture dislocation, and 7 with a posterior Monteggia injury
      associated with terrible triad fracture dislocation of the elbow. The association
      between coronoid fracture types and elbow fracture-dislocation patterns, as shown
      on 2-dimensional fracture and heat maps, was strongly significant. CONCLUSIONS:
      Our fracture maps and heat maps support the observation that specific patterns of
      traumatic elbow instability have correspondingly specific coronoid fracture
      patterns. Knowledge of these patterns is useful for planning management because
      it directs exposure and fixation and helps identify associated ligament injuries
      and fractures that might benefit from treatment. CLINICAL RELEVANCE: Two
      dimensional fracture and heat mapping techniques may help surgeons to predict the
      distribution of coronoid fracture lines associated with specific injury patterns.

PMID- 25070700
TI  - Treatment of supination deformity for obstetric brachial plexus injury: a
      systematic review and meta-analysis.
AB  - PURPOSE: To conduct a systematic review and meta-analysis of the literature
      evaluating treatment outcome for supination deformity in obstetric brachial
      plexus injury. METHODS: We included studies on brachial plexus and supination
      deformity with follow-up of at least one year and quantitative measurements of
      forearm mean passive pronation and position at rest. Meta-analysis was used to
      explore modifying factors. RESULTS: An elaborate search strategy resulted in 366
      studies, of which 13 were included totaling 238 patients (157 osteotomies and 71
      biceps rerouting). There was a 75 degrees  gain in position at rest and a 65
      degrees  gain in passive pronation for the osteotomy group, compared to a 79
      degrees  gain in position at rest for the biceps rerouting group. More severe
      deformities had greater gains. No influence of age was found. Important adverse
      effects were hardware failure and a biceps rupture. Recurrence in the osteotomy
      group was 20% to 40%, versus none in the soft-tissue group. CONCLUSIONS: This
      review showed an overall benefit for forearm osteotomies and for biceps rerouting
      for supination deformity with the gain proportionate to the severity of the
      deformity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 25070701
TI  - Facial myiasis and canthariasis associated with systemic lupus panniculitis: a
      case report.
AB  - BACKGROUND: Infestation of insects can cause myiasis due to dipetran larvae and
      canthariasis due to coleopteran larval or adult stages. OBJECTIVE: To report a
      case of facial myiasis and canthariasis in a patient known to have panniculitis
      due to systemic lupus erythematosus and autoimmune hemolytic anemia. METHOD:
      Larval and pupal stages of insects were recovered from the face of a patient,
      mounted, and identified. RESULT: Initially, the pupal stage of the common green
      bottle fly Lucilia sericata was extracted from the patient's face, treated, and
      then came back with secondary infestation caused by two species of beetles, the
      drugstore beetle, Stegobium paniceum, and a beetle of the genus Trogoderma.
      CONCLUSION: This is the first report on facial canthariasis due to larval stages
      caused by two species of beetles and recovery of pupal stages of the common green
      bottle fly.

PMID- 25070702
TI  - Ten-year long-term results after non-surgical management of hepatolithiasis,
      including cases with choledochoenterostomy.
AB  - BACKGROUND: Long-term follow-up of non-surgical procedures for the management of
      hepatolithiasis has been reported, but risk factors for mortality have not been
      properly evaluated. METHODS: We conducted a retrospective study of the case
      records of 121 patients with hepatolithiasis who underwent endoscopic retrograde
      cholangiopancreatography (ERCP), peroral cholangioscopy (POCS), percutaneous
      transhepatic cholangioscopy (PTCS), or conservative treatment at the Department
      of Gastroenterology of Chiba University Hospital between January 1980 and July
      2011. The primary outcome measure was mortality, defined as death due to
      hepatolithiasis (concomitant liver failure with cholangitis and
      cholangiocarcinoma). RESULTS: Complete clearance of intrahepatic stones was
      achieved in 22 (57.8%) of 38 patients by POCS, in 12 (66.7%) of 18 patients by
      ERCP, and in 10 (52.6%) of 18 patients by PTCS. The remaining 46 patients were
      treated conservatively. The mean follow-up period was 11.4 +/- 7.1 years (range,
      0.6-32.8). There were 14 hepatolithiasis-related deaths (11 with
      cholangiocarcinoma and three from liver failure with cholangitis) during the
      follow-up periods. Multivariate Cox proportional hazards analysis revealed liver
      atrophy (P = 0.015; HR = 3.98; 95% CI, 1.30-12.20) and congenital biliary
      dilatation after biliary-enteric anastomosis (P = 0.036; HR = 4.57; 95% CI, 1.11
      18.87) as significant risk factors for mortality. CONCLUSIONS: Analysis of the 10
      year long-term results after non-surgical management of hepatolithiasis
      identified liver atrophy and congenital biliary dilatation as risk factors for
      mortality. Patients with hepatic lobe atrophy should undergo a hepatectomy, if
      operable.

PMID- 25070703
TI  - Smartphone, tablet computer and e-reader use by people with vision impairment.
AB  - PURPOSE: Consumer electronic devices such as smartphones, tablet computers, and e
      book readers have become far more widely used in recent years. Many of these
      devices contain accessibility features such as large print and speech. Anecdotal
      experience suggests people with vision impairment frequently make use of these
      systems. Here we survey people with self-identified vision impairment to
      determine their use of this equipment. METHOD: An internet-based survey was
      advertised to people with vision impairment by word of mouth, social media, and
      online. Respondents were asked demographic information, what devices they owned,
      what they used these devices for, and what accessibility features they used.
      RESULTS: One hundred and thirty-two complete responses were received. Twenty-six
      percent of the sample reported that they had no vision and the remainder reported
      they had low vision. One hundred and seven people (81%) reported using a
      smartphone. Those with no vision were as likely to use a smartphone or tablet as
      those with low vision. Speech was found useful by 59% of smartphone users. Fifty
      one percent of smartphone owners used the camera and screen as a magnifier. Forty
      eight percent of the sample used a tablet computer, and 17% used an e-book
      reader. The most frequently cited reason for not using these devices included
      cost and lack of interest. CONCLUSIONS: Smartphones, tablet computers, and e-book
      readers can be used by people with vision impairment. Speech is used by people
      with low vision as well as those with no vision. Many of our (self-selected)
      group used their smartphone camera and screen as a magnifier, and others used the
      camera flash as a spotlight.

PMID- 25070704
TI  - Anthocyanins potentiate the activity of trastuzumab in human epidermal growth
      factor receptor 2-positive breast cancer cells in vitro and in vivo.
AB  - Human epidermal growth factor receptor 2 (HER2) has been found to be
      overexpressed in ~25% of invasive breast cancer and is significantly associated
      with a poor prognosis in breast cancer patients. The anthocyanins cyanidin-3
      glucoside (C3G) and peonidin-3-glucoside have been identified as potential drugs
      for the therapy of HER2-positive breast cancer. They have been used as
      supplements in targeted therapeutics and chemotherapeutics in Asia, however, the
      underlying mechanism remains to be elucidated. The aim of the present study was
      to investigate the synergism between C3G and trastuzumab (Trast). To address this
      question, the response to C3G, Trast and a combination of the two drugs, in three
      representative HER2-positive cell lines was evaluated. The combination treatments
      induced apoptosis, inhibited cell growth and affected HER2 and its downstream
      signaling pathway in MDA-MB-453, BT474 and HCC1569 cells, and the effects were
      synergistic. The combination of 3CG and Trast inhibited tumor growth in an in
      vivo xenograft model. The data from the present study suggested that C3G exhibits
      potent antitumor activity when combined with Trast under the investigated
      conditions.

PMID- 25070705
TI  - Teleradiology for remote consultation using iPad improves the use of health
      system human resources for paediatric fractures: prospective controlled study in
      a tertiary care hospital in Italy.
AB  - BACKGROUND: The growing cost of health care and lack of specialised staff have
      set e-Health high on the European political agenda. In a prospective study we
      evaluated the effect of providing images for remote consultation through an iPad
      on the number of in-hospital orthopaedic consultations for children with bone
      fractures. METHODS: Children from 0 to 18 years diagnosed with a bone fracture by
      the radiologist during the hours when an orthopaedic service is provided only on
      call were eligible for enrollment. Cases were enrolled prospectively during
      September and October 2013. A standard approach (verbal information only, no X
      Ray provided remotely) was compared to an experimental approach (standard
      approach plus the provision of X-ray for remote consultation through an iPad).
      The primary outcome was the number of orthopaedic in-hospital consultations that
      occurred. Other outcomes included: immediate activation of other services; time
      needed for decision-making; technical difficulties; quality of images and
      diagnostic confidence (on a likert scale of 1 to 10). RESULTS: Forty-two children
      were enrolled in the study. Number of in-hospital consultancies dropped from
      32/42 (76.1%) when no X-ray was provided to 16/42 (38%) when the X-rays was
      provided (p < 0.001). With remote X-ray consultation in 14/42 (33.3%) cases
      services such as surgery and plaster room could be immediately activated,
      compared to no service activated without teleradiology (p < 0.001). Average time
      for decision making was 23.4 +/- 21.8 minutes with remote X-ray consultation,
      compared to 56.2 +/- 16.1 when the X-ray was not provided (p < 0.001). The
      comparison between images on the iPad and on the standard system for X- Ray
      visualisation resulted in a non statistically significant difference in the
      quality of images (average score 9.89 +/- 0.37 vs 9.91 +/- 0.30; p = 0.79), and
      in non statistically significant difference in diagnostic confidence (average
      score 9.91 +/- 0.32 vs 9.92 +/- 0.31; p = 0.88). CONCLUSIONS: Remote X-ray
      consultation through Aycan OsiriX PRO and iPad should be considered as a means
      for reducing the need of in-hospital orthopaedic consultation during on-call
      times, and potentially decrease the cost of care for the health system. In the
      future, alternative systems less expensive than Aycan OsiriX PRO should be
      further developed and tested.

PMID- 25070706
TI  - A metabonomic analysis of the effect of quercetin on toxicity induced by chronic
      exposure to low-level dichlorvos in rat plasma.
AB  - A previous study of ours has reported that chronic exposure to low-level
      dichlorvos (DDVP, 7.2 mg per kg bw) damages the liver, interferes with fatty acid
      metabolism, and disturbs the antioxidant defense system in rats. This study aims
      to investigate whether or not quercetin can protect against DDVP-induced toxicity
      through metabonomics and to elucidate the mechanism underlying this protective
      effect. Rats were randomly assigned into the control group, DDVP-treated group,
      quercetin-treated group, and quercetin plus DDVP-treated group. DDVP and
      quercetin were administered to the rats daily via drinking water and gavage,
      respectively, continuously for 90 d. The metabonomic profiles of rat plasma were
      analyzed using ultra-performance liquid chromatography-mass spectrometry.
      Finally, 11 metabolites were identified, including those of quercetin,
      isorhamnetin, and quercetin-3-glucuronide. The 11 metabolites showed significant
      changes in some treatment groups compared with the control group. Arachidonic
      acid, phytosphingosine, and C16 sphinganine significantly decreased while p
      cresol, lysoPE (16:0/0:0), lysoPC (15:0/0:0), lysoPC (16:0/0:0), lysoPC
      (0:0/18:0), and tryptophan significantly increased in the DDVP-treated group
      compared with the control group. The tendency of the aforementioned metabolites
      to change was significantly ameliorated in the high-dose quercetin (50 mg per kg
      bw per day) plus DDVP-treated group compared with the DDVP-treated group.
      However, the levels of these metabolites in the high-dose quercetin plus DDVP
      treated group were still significantly different from those in the control group.
      The results indicate that high-dose quercetin (50 mg per kg bw per day) elicits a
      partial protective effect on DDVP-induced toxicity. The histopathology of the
      liver tissues was consistent with the above results. Quercetin demonstrated
      regulatory effects on the metabolism of lipids and amino acids, the antioxidant
      defense system, etc. Therefore, increasing the daily intake of quercetin can
      ameliorate the toxicity induced by chronic exposure to low-level DDVP residue in
      food and/or water. 

PMID- 25070708
TI  - Palladium-catalyzed carbonylations of aryl bromides using paraformaldehyde:
      synthesis of aldehydes and esters.
AB  - Carbonylation reactions represent useful tools for organic synthesis. However,
      the necessity to use gaseous carbon monoxide is a disadvantage for most organic
      chemists. To solve this problem, novel protocols have been developed for
      conducting palladium-catalyzed reductive carbonylations of aryl bromides and
      alkoxycarbonylations using paraformaldehyde as an external CO source (CO gas
      free). Hence, aromatic aldehydes and esters were synthesized in moderate to good
      yields. 

PMID- 25070707
TI  - Brain, liver, and serum salusin-alpha and -beta alterations in Sprague-Dawley
      rats with or without metabolic syndrome.
AB  - BACKGROUND: This metabolic syndrome (MetS) study was designed to investigate
      changes in expression of the neuropeptides salusin-alpha (Sal-alpha) and salusin
      beta (Sal-beta) in brain and liver tissue in response to obesity and related
      changes induced by high-fructose diet and explored how these changes were
      reflected in the circulating levels of Sal-alpha and Sal-b, as well as revealing
      how the lipid profile and concentrations of glucose and uric acid were altered.
      MATERIAL/METHODS: The study included 14 Sprague-Dawley rats. The control group
      was fed ad libitum on standard rat pellets, while the intervention group was
      given water with 10% fructose in addition to the standard rat pellet for 3
      months. Sal-alpha and Sal-beta concentrations in the serum and tissue
      supernatants were measured by ELISA, and immunohistochemical staining was used to
      demonstrate expression of the hormones in brain and liver. RESULTS: Sal-alpha and
      Sal-beta levels in both the serum and the brain and liver tissue supernatants
      were lower in the MetS group than the control group. Sal-alpha and Sal-beta were
      shown by immunohistochemistry to be produced in the brain epithelium, the
      supraoptic nucleus of the hypothalamus, and the liver hepatocytes. CONCLUSIONS:
      The decrease in Sal-alpha and Sal-beta might be involved in the etiopathology of
      the metabolic syndrome induced by fructose.

PMID- 25070709
TI  - MicroRNA: a new type of gene.

PMID- 25070710
TI  - Identification of miRNAs dysregulated in human foreskin keratinocytes (HFKs)
      expressing the human papillomavirus (HPV) Type 16 E6 and E7 oncoproteins.
AB  - Human papillomaviruses (HPVs) are associated with the pathogenesis of a variety
      of human cancers, including cervical and oropharyngeal cancers. The HPV E6 and E7
      oncogenes are usually expressed to high levels in these cancers. Previous studies
      have shown dysregulation of cellular microRNAs (miRNAs) in HPV-positive cell
      lines and cancer tissues and recent studies have identified a few miRNAs whose
      levels are altered in the presence of the viral E6 and E7 proteins. In order to
      identify all the cellular miRNAs whose expression may be affected by these
      oncoproteins, we carried out microarray analysis using human foreskin
      keratinocytes (HFKs) expressing either or both of these two proteins. These
      studies showed that 90 and 60 miRNAs were dysregulated in the presence of the E6
      or the E7 protein, respectively. Of these, 43 miRNAs were similarly affected in
      HFK-E6 and/or HFK-E7 when compared to control cells. The joint expression of E6
      and E7 proteins in HFKs caused changes in the levels of 64 miRNAs, of which 24
      were similarly affected in HFK-E6 and/or HFK-E7 cells relative to controls. The
      microarray experiments were validated by quantitative real-time RT-PCR analysis
      of several differentially expressed miRNAs. Several miRNAs dysregulated by the E6
      and/or E7 proteins are known to be altered in a variety of human cancers.
      Furthermore, previously known cellular targets of these miRNAs are involved in
      processes such as cell cycle regulation, apoptosis, cell-cell adhesion, cell
      mobility and proliferation, and alterations in their levels may contribute to HPV
      associated carcinogenesis. Taken together, the results of our studies suggest
      that high risk HPV E6 and E7 proteins share the ability to regulate a subset of
      cellular miRNAs. 

PMID- 25070711
TI  - Isolation of secreted microRNAs (miRNAs) from cell-conditioned media.
AB  - MicroRNAs (miRNAs) have been found to be stable in the circulation of cancer
      patients raising their potential as circulating biomarkers of disease. The
      specific source and role, however, of miRNAs in the circulation is unknown and
      requires elucidation to determine their true potential. In this study, along with
      primary tissue explants and primary stromal cells, three breast cancer cell lines
      were employed, including T47D, MDA-MB-231 and SK-BR-3. Tissue explants were
      harvested in theatre, with informed patient consent, and included tumour, tumour
      associated normal, and diseased lymph node samples. Cell-conditioned media
      containing all factors secreted by the cells were harvested. MiRNAs were
      extracted from samples using 5 different extraction techniques including the
      blood protocol, RNeasy(r) (Qiagen), miRNeasy(r)mini kit (Qiagen), mirVanaTM
      isolation kit (Ambion) and RNAqueous(r) kit (Ambion). MiRNAs were successfully
      isolated from all media samples collected from cell lines, primary cells and
      fresh tissue explants. However, there was remarkable variation in yield depending
      on the extraction method used. Aliquots of the same samples were extracted,
      revealing the two column extraction protocol of the mirVana(r) miRNA isolation
      kit to be the most suitable approach. A range of miRNAs, including miR-16, miR
      195, miR-497 and miR-10b, were successfully amplified. While miR-16 and miR-195
      were detected in media from both cell lines and tissue explants, miR-497 and miR
      10b were only detected in secretions from whole tissue explants. The ability to
      achieve reliable and reproducible miRNA yields from cell-conditioned media is
      vital for the successful amplification of miRNAs by RQ-PCR. 

PMID- 25070712
TI  - MiRNAs in bone diseases.
AB  - MicroRNAs (miRNAs), which mainly inhibit protein expression by targeting the
      3'UTR (untranslated region) of mRNAs, are known to play various roles in the
      pathogenesis of many different types of diseases. Specifically, in bone diseases,
      recent emphasis has been placed on the involvement of miRNAs in the
      differentiation and proliferation of bone and cartilage cells, particularly with
      regards to how these mechanisms contribute to bone homeostasis. In this review,
      we summarize miRNAs that are important in the differentiation and proliferation
      of bone cells, and specific miRNAs associated with bone diseases, such as
      osteoporosis, osteoarthritis and rheumatoid arthritis. This review also provides
      the perspective that miRNA studies will identify not only new mechanisms in basic
      bone research, but also potential novel diagnostic biomarkers and drug targets
      for bone diseases. 

PMID- 25070713
TI  - Novel microRNAs and microsatellite-like small RNAs in sexual and apomictic
      Boechera species.
AB  - Apomixis refers to plant asexual reproduction through seeds that give rise to
      progeny which are genotypically identical to the maternal parent. It has evolved
      from many different sexual taxa although the underlying genetic factors remain
      unknown. Previous analyses of the over-representation of transcription factors,
      in a comparison of microdissected ovules from apomictic and sexual Boechera,
      showed that many transcription factor mRNAs possessed microRNA (miRNAs) binding
      sites, thus pointing to miRNAs as potentially important factors that may be
      involved in the regulatory switch from sexual to apomictic reproduction. A
      microarray-based approach was used to identify (1) 673 microsatellitelike small
      RNAs (misRNAs) containing predominantly 2-7 repeats of (GAA)n/(CUU)n,
      (GCA)n/(CGU)n, (GGA)n/(CCU)n, (GGU)n/(CCA)n and (UGA)n/(ACU)n, and (2) 166 more
      typical non-repeat small RNAs. In total, 87 small RNAs were found to be located
      in cDNAs that could fold into stem-loop structures and thus represent miRNA
      molecules. In addition, 109 Boechera small RNAs including both misRNAs and non
      repeat small RNAs, showed significant homology to 407 Arabidopsis thaliana small
      RNAs including the A. thaliana pollen-specific ath-miR5021. This indicates that
      only a fraction of the identified small RNAs are unique to Boechera. Ten small
      RNAs were validated using a Northern blot assay on flower and leaf tissues, eight
      of which showed flower-specific expression with varying abundance. The potential
      binding sites of many of the misRNAs and non-repeat small RNAs occur
      predominantly in exonic regions. This feature coupled with their flower-specific
      pattern of expression is suggestive of their probable role in post
      transcriptional gene regulation. We propose that quantitative variation for
      misRNA target binding (and hence post-transcriptional gene regulation) could
      arise via microsatellite length polymorphisms occurring either in misRNA
      precursors or in their gene targets. 

PMID- 25070714
TI  - Small yet mighty - microRNAs in plant-microbe interactions.
AB  - Micro RNAs (miRNAs) are short non-coding RNAs of 20-24nt in length mediating RNA
      silencing, a eukaryotic, sequence-specific repressive gene regulation mechanism.
      In plants, miRNAs have a pivotal role during fundamental processes such as
      development, maintenance of genome integrity and abiotic stress responses. They
      originate from MIRNA genes that are transcribed by RNA polymerase II; MIRNA
      transcripts form imperfect fold-back structures that are further processed to
      miRNA duplexes. In Arabidopsis, over 180 MIRNA loci have been identified. Recent
      evidence shows that miRNAs are substantially implicated in regulating plant
      immunity. Pathogen attack triggers massive changes in the miRNA transcriptome;
      many of the altered miRNAs participate in controlling plant hormone pathways.
      Moreover, microorganisms are known to manipulate silencing pathways to counteract
      miRNA-mediated defenses. Thus far, miRNAs are believed to likely function as
      cardinal players in the concert of broad-spectrum disease resistance. Here, we
      summarize the highlights and latest findings of miRNAs as molecular regulators
      during plant-microbe interactions. 

PMID- 25070715
TI  - The course of headache in idiopathic intracranial hypertension: a 12-month
      prospective follow-up study.
AB  - BACKGROUND AND PURPOSE: Our aim was to prospectively describe the course of
      headache during the first year of idiopathic intracranial hypertension (IIH).
      METHODS: Patients with newly diagnosed IIH were consecutively included from
      December 2010 to June 2013. Treatment according to standard guidelines was
      initiated. Headache history was obtained by headache diaries and standardized
      interviews performed at baseline and after 1, 2, 3 and 12 months. Parallel
      changes in papilledema were assessed by optical coherence tomography (OCT). All
      patients had comprehensive neuro-ophthalmological examinations including
      automated perimetry. RESULTS: Forty-four patients were included. Thirty-five
      patients completed the 12-month follow-up. Dramatic improvement in headache
      occurred within the first weeks after diagnosis. After 1 year, 15 patients
      reported no or only infrequent headache. However, 15 of the remaining 20 patients
      reported sustained chronic headache. Early age of onset and high diagnostic
      intracranial pressure (ICP) were associated with better headache outcome (<=1
      headache days/month) after a year. Papilledema decreased rapidly within the first
      2 months of diagnosis. After 1 year, OCT measures had normalized. Visual outcome
      was excellent in most patients. CONCLUSIONS: Although headache in 43% of patients
      responded well to ICP management, sustained long-term headache was seen in the
      remaining patients, despite resolution of papilledema. Headache in IIH may thus
      be attributed to more complex mechanisms than ICP elevation alone. High ICP and
      young age were associated with better headache outcome. Early treatment according
      to standard guidelines seems sufficient to ensure excellent visual outcome in the
      vast majority of patients.

PMID- 25070716
TI  - DFT studies of oxygen dissociation on the 116-atom platinum truncated octahedron
      particle.
AB  - Density functional theory calculations are performed to investigate oxygen
      dissociation on 116-atom truncated octahedron platinum particles. This work
      builds on results presented previously [Jennings et al., Nanoscale, 2014, 6,
      1153], where it was shown that shell flexibility played an important role in
      facilitating fast oxygen dissociation. In this study, through investigation of
      the larger particle size, it is shown that oxygen dissociation on the (111) facet
      of pure platinum species is still aided by shell flexibility at larger sizes.
      Only the hollow sites close to the edges of the (111) facet mediate oxygen
      dissociation; oxygen is bound too weakly at other hollow sites for dissociation
      to occur. Further studies are performed on the (100) facet, which is larger for
      the Pt116 particle than for either the Pt38 or Pt79 ones. Much higher
      dissociation barriers are found on the (100) facet compared to the (111) facet,
      where the bridge sites are favourable for oxygen dissociation. 

PMID- 25070717
TI  - Impact of hydrophobic chain composition on amphiphilic macromolecule
      antiatherogenic bioactivity.
AB  - Amphiphilic macromolecules (AMs) composed of sugar backbones modified with
      branched aliphatic chains and a poly(ethylene glycol) (PEG) tail can inhibit
      macrophage uptake of oxidized low-density lipoproteins (oxLDL), a major event
      underlying atherosclerosis development. Previous studies indicate that AM
      hydrophobic domains influence this bioactivity through interacting with
      macrophage scavenger receptors, which can contain basic and/or hydrophobic
      residues within their binding pockets. In this study, we compare two classes of
      AMs to investigate their ability to promote athero-protective potency via
      hydrogen-bonding or hydrophobic interactions with scavenger receptors. A series
      of ether-AMs, containing methoxy-terminated aliphatic arms capable of hydrogen
      bonding, was synthesized. Compared to analogous AMs containing no ether moieties
      (alkyl-AMs), ether-AMs showed improved cytotoxicity profiles. Increasing AM
      hydrophobicity via incorporation of longer and/or alkyl-terminated hydrophobic
      chains yielded macromolecules with enhanced oxLDL uptake inhibition. These
      findings indicate that hydrophobic interactions and the length of AM aliphatic
      arms more significantly influence AM bioactivity than hydrogen-bonding. 

PMID- 25070718
TI  - Pin1: a molecular orchestrator in the heart.
AB  - Pin1 is an evolutionarily conserved peptidyl-prolyl isomerase that binds and
      changes the three-dimensional conformation of specific phospho-proteins. By
      regulating protein structure and folding, Pin1 affects the stability,
      interaction, and activity of a broad spectrum of target proteins, thus impacting
      upon diverse cellular processes. This review discusses the pivotal role Pin1
      plays in regulating cardiac pathophysiology by functioning as a "molecular
      orchestrator" of a myriad of signal transduction pathways in the heart. 

PMID- 25070719
TI  - Mesenchymal stem cells improve motor functions and decrease neurodegeneration in
      ataxic mice.
AB  - The main objective of this work is to demonstrate the feasibility of using bone
      marrow-derived stem cells in treating a neurodegenerative disorder such as
      Friedreich's ataxia. In this disease, the dorsal root ganglia of the spinal cord
      are the first to degenerate. Two groups of mice were injected intrathecally with
      mesenchymal stem cells isolated from either wild-type or Fxntm1Mkn/Tg(FXN)YG8Pook
      (YG8) mice. As a result, both groups presented improved motor skills compared to
      nontreated mice. Also, frataxin expression was increased in the dorsal root
      ganglia of the treated groups, along with lower expression of the apoptotic
      markers analyzed. Furthermore, the injected stem cells expressed the trophic
      factors NT3, NT4, and BDNF, which bind to sensory neurons of the dorsal root
      ganglia and increase their survival. The expression of antioxidant enzymes
      indicated that the stem cell-treated mice presented higher levels of catalase and
      GPX-1, which are downregulated in the YG8 mice. There were no significant
      differences in the use of stem cells isolated from wild-type and YG8 mice. In
      conclusion, bone marrow mesenchymal stem cell transplantation, both autologous
      and allogeneic, is a feasible therapeutic option to consider in delaying the
      neurodegeneration observed in the dorsal root ganglia of Friedreich's ataxia
      patients. 

PMID- 25070720
TI  - Sticking to minimum standards: implementing antibiotic stewardship in intensive
      care.
AB  - BACKGROUND: In Australia, antimicrobial stewardship programmes are a compulsory
      component of hospital accreditation. Good documentation around anti-microbial
      prescribing aids communication and can improve prescribing practice in
      environments with multiple decision makers. AIM: This study aims to develop and
      implement an intervention to improve antimicrobial prescribing practice in a 24
      bed intensive care unit in a tertiary referral adult hospital. METHODS: We
      conducted a four-phase (observation, reflection, implementation, evaluation)
      prospective collaborative before-after quality improvement study. Baseline audits
      and surveys of antimicrobial prescribing practices identified barriers to and
      enablers of good prescribing practice. A customised intervention was then
      implemented over 6 weeks and included a yellow medication record sticker,
      quarterly education sessions and intensive care unit-specific empiric
      antimicrobial prescribing guidelines. Post-implementation, the effects were
      monitored by serial antimicrobial prescribing audits for 1 year. The primary
      outcomes were clear documentation of the start date, the planned stop date or
      review date and the indication for an antibiotic. These were all considered the
      'minimum standards' for an antimicrobial prescription on the medication record.
      RESULTS: Documentation of minimum standards specifically addressed by the sticker
      improved (start date (72% to 90%, P < 0.001), stop date (16% to 63%, P < 0.001),
      antimicrobial indication documented on medication chart (58% to 83%, P < 0.01)).
      Overall, adherence to all three minimum standards (start date, stop date and
      indication) improved from 41/306 (13%) to 306/492 (63%) (P < 0.001). One-year
      post-implementation, the yellow sticker had become embedded into daily practice.
      CONCLUSION: A systematic approach to quality improvement combined with the
      implementation of a tailored, multi-faceted intervention can improve
      antimicrobial prescribing practices.

PMID- 25070721
TI  - The effect of a non-surgical orthopaedic physician on wait times to see a
      paediatric orthopaedic surgeon.
AB  - AIMS: High referral volumes to paediatric orthopaedic surgeons create long clinic
      waiting lists. The use of extended scope roles for doctors and health
      professionals is one strategy to address these wait times. We completed a 6-month
      trial of a non-surgical paediatric orthopaedic physician role (NSP) to help
      manage non-urgent referrals to our service from local general practitioners
      (GPs). METHODS: For a 6-month period, the majority of non-urgent GP referrals
      were assessed by a US-trained NSP. Wait times were compared between this period
      and the same time period in the previous year. Family and referrer satisfaction
      was determined through postal surveys. RESULTS: Over the trial period, the NSP
      saw a total of 155 new patient referrals, which represented 49% of all non-urgent
      GP referrals for the period. Before the trial, only 75% of non-urgent referrals
      were seen within 131 days (19 weeks) with 10% waiting more than 215 days (31
      weeks). By the end of the trial, 75% of referrals were seen within 55 days (8
      weeks) and 90% within 61 days (9 weeks). The most common outcome was discharge
      with management advice. 12% of patients were referred on to an orthopaedic
      surgeon but only 1% went on to a surgical wait list. Families and referrers
      reported high levels of satisfaction and only three patients discharged by the
      NSP were referred back for orthopaedic surgeon review. CONCLUSION: The NSP role
      was effective at reducing clinic wait times for patients with non-urgent
      paediatric orthopaedic conditions, while maintaining family and referrer
      satisfaction.

PMID- 25070722
TI  - [Pain medicine in teaching: Relatively late and quite early].

PMID- 25070723
TI  - [Comparison of two screening questionnaires for patients with low back pain.
      Collation of risk factors for chronification].
AB  - BACKGROUND: Screening for risk factors for chronic low back pain (LBP) (yellow
      flags) is recommended by clinical guidelines. Various questionnaires to assess
      yellow flags have been proposed. OBJECTIVES: The aim of this study was to compare
      the prognostic validity of two screening questionnaires. MATERIAL AND METHODS:
      This was a prospective observational study with 241 LBP patients from 9 general
      practitioners, 4 orthopedic surgeons and 2 pain clinics. We compared the Orebro
      musculoskeletal pain questionnaire (OMSPQ) and the Heidelberg short questionnaire
      (HKF-R10) which were completed by all patients at inclusion before the
      consultation. Primary outcomes were assessed after 3 months by mail. Clinical
      endpoints were pain intensity, disability and more than two follow-up
      consultations. RESULTS: The sensitivity of the HKF-R10 to predict the primary
      outcome ranged from 81 % to 88 %, while the specificity was much lower (37-47 %).
      The OMSPQ showed an opposite pattern with a low sensitivity ranging from 50 % to
      58 % but a higher specificity (77-80 %). In patients initially classified as
      having chronic LBP (n = 81), using the questionnaires as a diagnostic tool, the
      sensitivity of both questionnaires increased but specificity decreased. Single
      items may perform better with regard to primary outcome than the sum scores.
      CONCLUSION: Both screening questionnaires for chronic LBP have insufficient
      diagnostic and prognostic validity for routine use in ambulatory care. Further
      studies are needed to improve diagnostic and prognostic validity and to elaborate
      criteria for a targeted use of screening questionnaires to guide therapeutic
      interventions.

PMID- 25070724
TI  - [Pain-induced attention allocation effects versus distraction from pain.
      Competition over attention resources].

PMID- 25070726
TI  - Retinal pathology detected by optical coherence tomography in an animal model of
      Parkinson's disease.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a noninvasive procedure for
      analysis of retinal morphology. Significant changes in the thickness of the
      peripapillary retinal nerve fiber layer (RNFL) in Parkinson's disease (PD) have
      been reported, and the current study was performed to examine whether such
      changes can also be detected in an animal model of PD. METHODS: Optical coherence
      tomography measurements of peripapillary RNFL thickness, macula volume, and
      foveal thickness were obtained from 10 normal and five 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-treated cynomolgus monkeys with stable Parkinsonian
      signs. RESULTS: Average RNFL thickness was significantly decreased in
      Parkinsonian monkeys compared with controls, with statistically significant RNFL
      thinning found in nasal and inferior quadrants. Macula volume and foveal
      thickness were also significantly reduced in Parkinsonian animals compared with
      controls. CONCLUSIONS: As described in PD, RNFL thinning, reduced macula volume,
      and reduced foveal thickness also occurs in monkeys with MPTP-induced
      Parkinsonism. These findings pave the way for additional studies in which OCT may
      be used to track changes in the retina that might be present very early in the PD
      pathological process, perhaps preceding the onset of motor signs.

PMID- 25070725
TI  - [Neuromodulation for neuropathic pain].
AB  - In pain therapy neurostimulation procedures have replaced the previously used
      lesional methods with only very few exceptions. This is especially true for
      neuropathic pain, i.e. pain which occurs as a direct consequence of a lesion or
      disease of the somatosensory system. Nowadays, various stimulation procedures are
      included in the neurosurgical and anesthesiological armamentarium for pain
      therapy, depending on the site of damage. This article gives an overview of the
      currently used invasive stimulation procedures and the indications. 

PMID- 25070727
TI  - Highly efficient synthesis of a tristable molecular shuttle and its controlled
      motion under chemical stimuli.
AB  - According to the threading-followed-by-stoppering approach, a tristable molecular
      shuttle could be efficiently synthesized in 76% yield using a K(+) ion template
      and a bulky isocyanate stopper. This high yield was reasoned from the combination
      of the powerful template effect and highly effective stoppering reaction. Through
      detailed studies of the (1)H NMR, HSQC and 2D-ROESY NMR spectra, it was proved
      that the shuttling of the triptycene-derived macrocycle between the three
      stations of pyromellitic diimide (PmI), anthraquinone (AQ) and N-methyltriazolium
      (MtA) could be unambiguously achieved in a chemical way. The three distinct
      stable states of the molecular shuttle could be further evidenced by analyzing
      the high-resolution electrospray ionization (HR-ESI) mass spectra and UV-Vis
      spectra. 

PMID- 25070728
TI  - Discovery of highly specific protein markers for the identification of biological
      stains.
AB  - DNA profiling has transformed the field of forensic biology by making it possible
      to individualize biological stains. The identification of the stain itself,
      however, continues to present forensic serologists with significant challenges.
      Current antibody- and enzyme activity-based assays yield only presumptive results
      as detection in nontarget body fluids or cross-reactivity with nonhuman sources
      have both been well documented. For other critical body fluids such as vaginal
      and menstrual fluids, there are no commercial tests at all. Using a three
      pronged, comparative proteomic strategy based on proteome fractionation by HPLC
      followed by MS, a panel of 29 candidate protein biomarkers have been proposed as
      highly specific indicators of human saliva, urine, seminal fluid, vaginal fluid,
      peripheral blood, and menstrual fluid. The combination of consistent
      identification by multiple strategies in the current study; confirmation in
      independently compiled proteomic databases; and information on tissue expression
      and/or functionality from the proteomic literature all support the proposition
      that these proteins will have utility as reliable biomarkers of their target body
      fluids. The identification of candidate high-specificity protein biomarkers for
      human body fluids encountered in forensic investigations lays the foundation for
      the development of faster and more reliable approaches to the serological
      analysis of evidentiary stains. 

PMID- 25070729
TI  - Radioresistance of cancer stem-like cell derived from canine tumours.
AB  - Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are a small
      subpopulation of cancer cells that are responsible for the initiation, recurrence
      and metastasis of cancer. We previously demonstrated that, using the Hoechst
      33342 dye-based side population technique, CSCs/CICs in canine lung
      adenocarcinoma cell line exist. In this study, as CSCs/CICs are known to form
      spheres in anchorage-independent environment in vitro, we evaluated the stemness
      of spheroid cells derived from canine lung adenocarcinoma and osteosarcoma cells
      by expression of stemness markers, and investigated radioresistance. Spheroid
      cells showed greater expression of stemness markers Oct-4 and CD133 gene than
      those of adherent-cultured cells. In nude mouse xenograft models, spheroid cells
      showed higher tumourigenic ability than adherent-cultured cells. In addition,
      spheroid cells showed significantly resistant against radioactivity as compared
      with adherent-cultured cells. These results suggest that spheroid cells could
      possess stemness and provide a CSCs/CICs research tool to investigate CSCs/CICs
      of canine tumour cells. 

PMID- 25070730
TI  - "Who's afraid?": attitudes of midwives to the use of information and
      communication technologies (ICTs) for delivery of pregnancy-related health
      information.
AB  - BACKGROUND: Usage rates for information and communication technologies (ICTs) in
      healthcare have been increasing in recent years, but often lag behind general
      usage rates for populations as a whole. Research into such differential rates of
      ICT use across different segments of the population has identified a number of
      possible causal factors that limit usage. AIM: The research investigated
      midwives' attitudes and experiences of ICT use to identify potential causal
      factors that encourage or inhibit their usage in antenatal care. METHODS: Semi
      structured interviews, focus groups and short surveys were conducted with
      midwives who provide antenatal education at an Australian metropolitan hospital.
      Thematic and statistical analyses were used to interpret the data. FINDINGS:
      Although midwives recognised the potential benefits of using ICTs to deliver
      pregnancy-related health information many had reservations about their use in
      everyday work. These reservations centred on lack of training in use of ICTs, the
      perceived legal risks associated with social media, potential violations of
      patient privacy, misdiagnosis and misunderstandings between midwife and client.
      CONCLUSION: Midwives face a number of barriers to effective use of ICTs in
      healthcare including material access, skills access, usage access and
      motivational access. Motivational access appears to be a key concern due to the
      high perception of risk associated with social media in particular. Reducing the
      motivational barriers through a range of interventions with midwifery staff may
      assist in overcoming other barriers to ICT use in antenatal care. Further
      research is required to determine whether these findings are generalisable to
      other healthcare contexts.

PMID- 25070731
TI  - Remote access and care: A comparison of Queensland women's maternity care
      experience according to area of residence.
AB  - BACKGROUND: This study fills a gap in the literature with a quantitative
      comparison of the maternity care experiences of women in different geographic
      locations in Queensland, Australia. METHOD: Data from a large-scale survey were
      used to compare women's care experiences according to Australian Standard
      Geographical Classification (major city, inner regional, outer regional, remote
      and very remote). RESULTS: Compared to the other groups, women from remote or
      very remote areas were more likely to be younger, live in an area with poorer
      economic resources, identify as Aboriginal and/or Torres Strait Islander and give
      birth in a public facility. They were more likely to travel to another city, town
      or community for birth. In adjusted analyses women from remote areas were less
      likely to have interventions such as electronic fetal monitoring, but were more
      likely to give birth in an upright position and be able to move around during
      labour. Women from remote areas did not differ significantly from women from
      major cities in their satisfaction with interpersonal care. Antenatal and
      postpartum care was lacking for rural women. In adjusted analyses they were much
      less likely to have booked for maternity care by 18 weeks gestation, to be
      telephoned or visited by a care provider in the first 10 days after birth.
      Despite these differences, women from remote areas were more likely to be
      breastfeeding at 13 weeks and confident in caring for their baby at home.
      CONCLUSIONS: Findings support qualitative assertions that remote and rural women
      are disadvantaged in their access to antenatal and postnatal care by the need to
      travel for birth, however, other factors such as age were more likely to be
      significant barriers to high quality interpersonal care. Improvements to
      maternity services are needed in order to address inequalities in maternity care
      particularly in the postnatal period.

PMID- 25070732
TI  - Association between HTR7 genetic polymorphisms and alcohol dependence, using the
      alcohol use disorders identification test (AUDIT).
AB  - BACKGROUND: A recent genome-wide association study has identified 5
      hydroxytrytamine (serotonin) receptor 7, adenylate cyclase-coupled (HTR7) as a
      risk gene for alcohol dependence. In addition, the serotonergic system has been
      considered as a modulator that plays an important role in alcohol use disorders.
      Functional, pharmacological, and genetic studies of serotonin neurotransmission
      have revealed that serotonin receptors are potential targets for the treatment of
      alcohol use disorders. The aim of this study is to investigate whether
      associations between HTR7 genetic polymorphisms and alcohol dependence could be
      replicated. METHODS: This study genotyped a total of 22 common single nucleotide
      polymorphisms (SNPs) in 459 alcoholic patients and 444 nonalcoholic controls.
      RESULTS: Logistic regression analysis of the case-control study, controlling for
      age and sex as covariates, showed nominal associations of 7 SNPs (p = 0.02 to
      0.04; odds ratio = 0.60 to 1.35). In further linear regression analysis based on
      the Alcohol Use Disorders Identification Test score for alcohol dependence, 8
      SNPs and 3 haplotypes showed relatively significant associations with alcohol
      dependence (minimum p = 0.001; p(corr) = 0.02). CONCLUSIONS: Although further
      replications and functional evaluations are needed, our findings suggest that
      genetic variations of HTR7 may contribute to the predisposition for alcohol
      dependence.

PMID- 25070733
TI  - The effect of inhaled nitric oxide on the carrageenan-induced paw edema.
AB  - Inhaled nitric oxide therapy reaches not only pulmonary vessels, but also other
      vasculatures, presenting anti-inflammatory effects. Therefore, this study
      investigated the effects of inhaled nitric oxide on a mice model of carrageenan
      induced paw edema. Paw edema was induced in male Swiss mice (20-30 g) by
      subplantar injection of carrageenan (0.05 ml of a 1% suspension in 0.9% saline).
      The evaluation of time-course edema (mililiter) was measured by plethysmometry
      until 12 h following carrageenan administration. Thirty minutes after carrageenan
      injection, some groups received inhaled nitric oxide (300 ppm at variable doses
      and times) or Indometacin (INDO 5 mg/Kg, v.o), while others received sildenafil
      (1 mg/Kg, i.p) or rolipram (3 mg/Kg, i.p.) with or without inhaled nitric oxide.
      Paws were assessed for edema levels by plethysmometry, mieloperoxidase activity
      and histological analysis. Inhaled nitric oxide significantly reduced carrageenan
      induced paw edema, mieloperoxidase activity and inflammatory infiltrate, although
      similar results were also observed in sildenafil and rolipram treated groups. In
      addition, significant effects between inhaled nitric oxide with pharmacological
      therapy was observed. Inhaled nitric oxide presents anti-inflammatory effects on
      carrageenan-induce paw edema, as observed through reduced edema, mieloperoxidase
      activity and neutrophil infiltration, indicating that inhaled nitric oxide
      therapy goes beyond lung vascular effects.

PMID- 25070734
TI  - The Preconception Stress and Resiliency Pathways Model: a multi-level framework
      on maternal, paternal, and child health disparities derived by community-based
      participatory research.
AB  - Emerging evidence supports the theoretical and clinical importance of the
      preconception period in influencing pregnancy outcomes and child health.
      Collectively, this evidence affirms the need for a novel, integrative theoretical
      framework to design future investigations, integrate new findings, and identify
      promising, evidence-informed interventions to improve intergenerational health
      and reduce disparities. This article presents a transdisciplinary framework
      developed by the NIH Community Child Health Network (CCHN) through community
      based participatory research processes. CCHN developed a Preconception Stress and
      Resiliency Pathways (PSRP) model by building local and multi-site community
      academic participatory partnerships that established guidelines for research
      planning and decision-making; reviewed relevant findings diverse disciplinary and
      community perspectives; and identified the major themes of stress and resilience
      within the context of families and communities. The PSRP model focuses on inter
      relating the multiple, complex, and dynamic biosocial influences theoretically
      linked to family health disparities. The PSRP model borrowed from and then added
      original constructs relating to developmental origins of lifelong health,
      epigenetics, and neighborhood and community influences on pregnancy outcome and
      family functioning (cf. MCHJ 2014). Novel elements include centrality of the
      preconception/inter-conception period, role of fathers and the parental
      relationship, maternal allostatic load (a composite biomarker index of cumulative
      wear-and-tear of stress), resilience resources of parents, and local neighborhood
      and community level influences (e.g., employment, housing, education, health
      care, and stability of basic necessities). CCHN's integrative framework embraces
      new ways of thinking about how to improve outcomes for future generations, by
      starting before conception, by including all family members, and by engaging the
      community vigorously at multiple levels to promote resiliency, reduce chronic and
      acute stressors, and expand individualized health care that integrates promotive
      and prevention strategies. If widely adopted, the PSRP model may help realize the
      goal of sustaining engagement of communities, health and social services
      providers, and scientists to overcome the siloes, inefficiencies, and lack of
      innovation in efforts to reduce family health disparities. Model limitations
      include tremendous breadth and difficulty measuring all elements with precision
      and sensitivity. 

PMID- 25070735
TI  - Predictors of children's health insurance coverage discontinuity in 1998 versus
      2009: parental coverage continuity plays a major role.
AB  - To identify predictors of coverage continuity for United States children and
      assess how they have changed in the first 12 years since implementation of the
      Children's Health Insurance Program in 1997. Using data from the nationally
      representative Medical Expenditure Panel Survey, we used logistic regression to
      identify predictors of discontinuity in 1998 and 2009 and compared differences
      between the 2 years. Having parents without continuous coverage was the greatest
      predictor of a child's coverage gap in both 1998 and 2009. Compared to children
      with at least one parent continuously covered, children whose parents did not
      have continuous coverage had a significantly higher relative risk (RR) of a
      coverage gap [RR 17.96, 95 % confidence interval (CI) 14.48-22.29 in 1998; RR
      12.88, 95 % CI 10.41-15.93 in 2009]. In adjusted models, parental continuous
      coverage was the only significant predictor of discontinuous coverage for
      children (with one exception in 2009). The magnitude of the pattern was higher
      for privately-insured children [adjusted relative risk (aRR) 29.17, 95 % CI 20.99
      40.53 in 1998; aRR 25.54, 95 % CI 19.41-33.61 in 2009] than publicly-insured
      children (aRR 5.72, 95 % CI 4.06-8.06 in 1998; aRR 4.53, 95 % CI 3.40-6.04 in
      2009). Parental coverage continuity has a major influence on children's coverage
      continuity; this association remained even after public health insurance
      expansions for children. The Affordable Care Act will increase coverage for many
      adults; however, 'churning' on and off programs due to income fluctuations could
      result in coverage discontinuities for parents. If parental coverage instability
      persists, these discontinuities may continue to have a negative impact on
      children's coverage stability as well. 

PMID- 25070736
TI  - Staphylococcus epidermidis agr quorum-sensing system: signal identification,
      cross talk, and importance in colonization.
AB  - Staphylococcus epidermidis is an opportunistic pathogen that is one of the
      leading causes of medical device infections. Global regulators like the agr
      quorum-sensing system in this pathogen have received a limited amount of
      attention, leaving important questions unanswered. There are three agr types in
      S. epidermidis strains, but only one of the autoinducing peptide (AIP) signals
      has been identified (AIP-I), and cross talk between agr systems has not been
      tested. We structurally characterized all three AIP types using mass spectrometry
      and discovered that the AIP-II and AIP-III signals are 12 residues in length,
      making them the largest staphylococcal AIPs identified to date. S. epidermidis
      agr reporter strains were developed for each system, and we determined that cross
      inhibitory interactions occur between the agr type I and II systems and between
      the agr type I and III systems. In contrast, no cross talk was observed between
      the type II and III systems. To further understand the outputs of the S.
      epidermidis agr system, an RNAIII mutant was constructed, and microarray studies
      revealed that exoenzymes (Ecp protease and Geh lipase) and low-molecular-weight
      toxins were downregulated in the mutant. Follow-up analysis of Ecp confirmed the
      RNAIII is required to induce protease activity and that agr cross talk modulates
      Ecp activity in a manner that mirrors the agr reporter results. Finally, we
      demonstrated that the agr system enhances skin colonization by S. epidermidis
      using a porcine model. This work expands our knowledge of S. epidermidis agr
      system function and will aid future studies on cell-cell communication in this
      important opportunistic pathogen. 

PMID- 25070737
TI  - NifA- and CooA-coordinated cowN expression sustains nitrogen fixation by
      Rhodobacter capsulatus in the presence of carbon monoxide.
AB  - Rhodobacter capsulatus fixes atmospheric dinitrogen via two nitrogenases, Mo- and
      Fe-nitrogenase, which operate under different conditions. Here, we describe the
      functions in nitrogen fixation and regulation of the rcc00574 (cooA) and rcc00575
      (cowN) genes, which are located upstream of the structural genes of Mo
      nitrogenase, nifHDK. Disruption of cooA or cowN specifically impaired Mo
      nitrogenase-dependent growth at carbon monoxide (CO) concentrations still
      tolerated by the wild type. The cooA gene was shown to belong to the Mo
      nitrogenase regulon, which is exclusively expressed when ammonium is limiting.
      Its expression was activated by NifA1 and NifA2, the transcriptional activators
      of nifHDK. AnfA, the transcriptional activator of Fe-nitrogenase genes, repressed
      cooA, thereby counteracting NifA activation. CooA activated cowN expression in
      response to increasing CO concentrations. Base substitutions in the presumed CooA
      binding site located upstream of the cowN transcription start site abolished cowN
      expression, indicating that cowN regulation by CooA is direct. In conclusion, a
      transcription factor-based network controls cowN expression to protect Mo
      nitrogenase (but not Fe-nitrogenase) under appropriate conditions. 

PMID- 25070738
TI  - Coordinate control of virulence gene expression in Francisella tularensis
      involves direct interaction between key regulators.
AB  - In Francisella tularensis, the putative DNA-binding protein PigR works in concert
      with the SspA protein family members MglA and SspA to control the expression of
      genes that are essential for the intramacrophage growth and survival of the
      organism. MglA and SspA form a complex that interacts with RNA polymerase (RNAP),
      and this interaction between the MglA-SspA complex and RNAP is thought to be
      critical to its regulatory function. How PigR works in concert with the MglA-SspA
      complex is not known; previously published findings differ over whether PigR
      interacts with the MglA-SspA complex, leading to disparate models for how PigR
      and the MglA-SspA complex exert their regulatory effects. Here, using a
      combination of genetic assays, we identify mutants of MglA and SspA that are
      specifically defective for interaction with PigR. Analysis of the MglA and SspA
      mutants in F. tularensis reveals that interaction between PigR and the MglA-SspA
      complex is essential in order for PigR to work coordinately with MglA and SspA to
      positively regulate the expression of virulence genes. Our findings uncover a
      surface of the MglA-SspA complex that is important for interaction with PigR and
      support the idea that PigR exerts its regulatory effects through an interaction
      with the RNAP-associated MglA-SspA complex. 

PMID- 25070739
TI  - Communication, cooperation, and social interactions: a report from the third
      Young Microbiologists Symposium on microbe signalling, organisation, and
      pathogenesis.
AB  - The third Young Microbiologists Symposium took place on the vibrant campus of the
      University of Dundee, Scotland, from the 2nd to 3rd of June 2014. The symposium
      attracted over 150 microbiologists from 17 different countries. The significant
      characteristic of this meeting was that it was specifically aimed at providing a
      forum for junior scientists to present their work. The meeting was supported by
      the Society for General Microbiology and the American Society for Microbiology,
      with further sponsorship from the European Molecular Biology Organization, the
      Federation of European Microbiological Societies, and The Royal Society of
      Edinburgh. In this report, we highlight some themes that emerged from the many
      exciting talks and poster presentations given by the young and talented
      microbiologists in the area of microbial gene expression, regulation, biogenesis,
      pathogenicity, and host interaction. 

PMID- 25070740
TI  - Pleiotropic and epistatic behavior of a ring-hydroxylating oxygenase system in
      the polycyclic aromatic hydrocarbon metabolic network from Mycobacterium
      vanbaalenii PYR-1.
AB  - Despite the considerable knowledge of bacterial high-molecular-weight (HMW)
      polycyclic aromatic hydrocarbon (PAH) metabolism, the key enzyme(s) and its
      pleiotropic and epistatic behavior(s) responsible for low-molecular-weight (LMW)
      PAHs in HMW PAH-metabolic networks remain poorly understood. In this study, a
      phenotype-based strategy, coupled with a spray plate method, selected a
      Mycobacterium vanbaalenii PYR-1 mutant (6G11) that degrades HMW PAHs but not LMW
      PAHs. Sequence analysis determined that the mutant was defective in pdoA2,
      encoding an aromatic ring-hydroxylating oxygenase (RHO). A series of metabolic
      comparisons using high-performance liquid chromatography (HPLC) analysis revealed
      that the mutant had a lower rate of degradation of fluorene, anthracene, and
      pyrene. Unlike the wild type, the mutant did not produce a color change in
      culture media containing fluorene, phenanthrene, and fluoranthene. An Escherichia
      coli expression experiment confirmed the ability of the Pdo system to oxidize
      biphenyl, the LMW PAHs naphthalene, phenanthrene, anthracene, and fluorene, and
      the HMW PAHs pyrene, fluoranthene, and benzo[a]pyrene, with the highest enzymatic
      activity directed toward three-ring PAHs. Structure analysis and PAH substrate
      docking simulations of the Pdo substrate-binding pocket rationalized the
      experimentally observed metabolic versatility on a molecular scale. Using
      information obtained in this study and from previous work, we constructed an RHO
      centric functional map, allowing pleiotropic and epistatic enzymatic explanation
      of PAH metabolism. Taking the findings together, the Pdo system is an RHO system
      with the pleiotropic responsibility of LMW PAH-centric hydroxylation, and its
      epistatic functional contribution is also crucial for the metabolic quality and
      quantity of the PAH-MN. 

PMID- 25070741
TI  - Self-association is required for occupation of adjacent binding sites in
      Pseudomonas aeruginosa type III secretion system promoters.
AB  - ExsA is a member of the AraC/XylS family of transcriptional regulators and is
      required for expression of the Pseudomonas aeruginosa type III secretion system
      (T3SS). All P. aeruginosa T3SS promoters contain two adjacent binding sites for
      monomeric ExsA. The amino-terminal domain of ExsA (NTD) is thought to mediate
      interactions between the ExsA monomers bound to each site. Threading the NTD onto
      the AraC backbone revealed an alpha-helix that likely serves as the primary
      determinant for dimerization. In this study, we performed alanine scanning
      mutagenesis of the ExsA alpha-helix (residues 136 to 152) to identify
      determinants required for self-association. Residues L137, C139, L140, K141, and
      L148 exhibited self-association defects and were required for maximal activation
      by ExsA. Disruption of self-association resulted in decreased binding to T3SS
      promoters, particularly loss of binding by the second ExsA monomer. Removing the
      NTD or increasing the space between the ExsA-binding sites restored the ability
      of the second ExsA monomer to bind the PexsC promoter. This finding indicated
      that, in the absence of self-association, the NTD prevents binding by a second
      monomer. Similar findings were seen with the PexoT promoter; however, binding of
      the second ExsA monomer in the absence of self-association also required the
      presence of a high-affinity site 2. Based on these data, ExsA self-association is
      necessary to overcome inhibition by the NTD and to compensate for low-affinity
      binding sites, thereby allowing for full occupation and activation of ExsA
      dependent promoters. Therefore, ExsA self-association is indispensable and
      provides an attractive target for antivirulence therapies. 

PMID- 25070742
TI  - Can the health system deliver? Determinants of rural Liberians' confidence in
      health care.
AB  - BACKGROUND: Following a protracted civil war, Liberia is rebuilding its health
      system. One of the aims of reconstruction is to expand access to health care to a
      previously underserved rural population. OBJECTIVE: This study analysed the
      determinants of Liberians' confidence in their ability to obtain needed care for
      themselves or their children in case of serious illness. METHODS: A cross
      sectional survey of 1435 adults in Nimba County, Liberia was conducted. Logistic
      regression models were estimated with reported ability to obtain needed health
      services for serious illness as the dependent variable, and demographics, health
      need, health system characteristics and informal health care as independent
      variables. RESULTS: Overall, 50.56% of respondents reported that they could
      obtain needed services for themselves or their children. Confidence in the
      ability to obtain care increased with education [odds ratio (OR) 1.62, 95%
      confidence interval (CI): 1.19-2.21] and poor physical health in the past 30 days
      (OR 1.38, 95% CI: 1.01-1.88), and decreased with poverty (OR 0.66, 95% CI: 0.47
      0.93), exposure to previous trauma (OR 0.50, 95% CI: 0.36-0.71), dissatisfaction
      with respondent's last formal health visit (OR = 0.70, 95% CI: 0.54-0.91) and
      high utilization of the informal health sector (OR = 0.84, 95% CI: 0.73-0.96). No
      correlation was found between health system confidence and being female, being 35
      years old or younger, formal health sector use, being within an hour of a clinic
      and the closest clinic having basic capabilities. CONCLUSIONS: Respondents'
      experiences with the health care system had a greater correlation with their
      confidence in obtaining needed health care than proximity or quality of medical
      equipment in health clinics. Despite pro-poor policies guiding health system
      reconstruction, poor and less educated individuals have less confidence that the
      health system can meet their health needs.

PMID- 25070743
TI  - Proliferation and odontogenic differentiation of BMP2 gene-transfected stem cells
      from human tooth apical papilla: an in vitro study.
AB  - Stem cells from the apical papilla (SCAP) have odontogenic potential, which plays
      a pivotal role in the root dentin development of permanent teeth. Human bone
      morphogenetic protein 2 (BMP2) is a well-known gene that participates in
      regulating the odontogenic differentiation of dental tissue-derived stem cells.
      However, little is known regarding the effects of the BMP2 gene on the
      proliferation and odontogenic differentiation of SCAP. This study aimed to
      evaluate the odontogenic differentiation potential of lentiviral-mediated BMP2
      gene-transfected human SCAP (SCAP/BMP2) in vitro. SCAP were isolated by enzymatic
      dissociation of human teeth apical papillae. The multipotential of SCAP was
      verified by their osteogenic and adipogenic differentiation characteristics. The
      phenotype of SCAP was evaluated by flow cytometry (FCM). The proliferation status
      of the blank vector-transfected SCAP (SCAP/Vector) and SCAP/BMP2 was analyzed by
      a cell counting kit-8 (CCK-8). Odontogenic genes, including alkaline phosphatase
      (ALP), osteocalcin (OCN), dentin sialophosphoprotein (DSPP) and dentin matrix
      protein 1 (DMP1) of the two groups of cells were evaluated by quantitative
      polymerase chain reaction (qPCR). ALP staining and alizarin red (AR) staining of
      the cells was performed on the 16th day after transfection. In vitro results of
      CCK-8, qPCR, ALP and AR staining demonstrated that: i) SCAP/BMP2 had a comparable
      proliferation rate to SCAP/Vector; ii) SCAP/BMP2 presented significantly better
      potential to differentiate into odontoblasts compared to SCAP/Vector by
      upregulating ALP, OCN, DSPP and DMP1 genes; iii) more ALP granules and
      mineralized deposits were formed by SCAP/BMP2 as compared to SCAP/Vector. The
      results suggested that lentiviral-mediated BMP2 gene transfection enhances the
      odontogenic differentiation capacity of human SCAP in vitro.

PMID- 25070745
TI  - Generalized eruptive keratoacanthoma: a diagnostic and therapeutic challenge.
AB  - BACKGROUND: Generalized eruptive keratoacanthoma (GEKA) is an extremely rare
      variant of keratoacanthoma that poses significant diagnostic and therapeutic
      challenges. PATIENTS: The study included three patients presenting with highly
      pruritic, generalized eruption of numerous small skin and flesh-colored
      follicular papules. They were mainly distributed on the face, neck, and trunk.
      Few larger nodules were also present. Mask-like facies, mucosal involvement, and
      ectropion were evident in two patients. Family history was irrelevant, and
      general examination was unremarkable. RESULTS: Histopathological examination
      revealed typical features of keratoacanthoma, particularly in the larger lesions.
      Routine laboratory tests were normal, and ultrasonography and computed tomography
      revealed no evidence of malignancy. Based on the clinicopathological correlation,
      the diagnosis of our cases was GEKA of Grzybowski. Acitretin 1 mg/kg per day and
      methotrexate 15 mg/week for three months were associated with mild or no
      response. Cyclophosphamide pulse therapy 1 g/month for six months was associated
      with complete clearance of the lesions in the first two patients, while the third
      was lost to follow-up after failure of acitretin therapy. CONCLUSION: Because of
      the extreme rarity of reported cases, the common absence of classic large lesions
      of keratoacanthoma, the atypical histological presentations in some cases, and
      absence of a uniformly effective therapeutic approach, we believe that GEKA still
      represents a diagnostic and therapeutic challenge. Cyclophosphamide pulse therapy
      is a promising alternative to oral retinoids.

PMID- 25070744
TI  - Methylene blue attenuates traumatic brain injury-associated neuroinflammation and
      acute depressive-like behavior in mice.
AB  - Traumatic brain injury (TBI) is associated with cerebral edema, blood brain
      barrier breakdown, and neuroinflammation that contribute to the degree of injury
      severity and functional recovery. Unfortunately, there are no effective proactive
      treatments for limiting immediate or long-term consequences of TBI. Therefore,
      the objective of this study was to determine the efficacy of methylene blue (MB),
      an antioxidant agent, in reducing inflammation and behavioral complications
      associated with a diffuse brain injury. Here we show that immediate MB infusion
      (intravenous; 15-30 minutes after TBI) reduced cerebral edema, attenuated
      microglial activation and reduced neuroinflammation, and improved behavioral
      recovery after midline fluid percussion injury in mice. Specifically, TBI
      associated edema and inflammatory gene expression in the hippocampus were
      significantly reduced by MB at 1 d post injury. Moreover, MB intervention
      attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1beta,
      tumor necrosis factor alpha) in enriched microglia/macrophages 1 d post injury.
      Cell culture experiments with lipopolysaccharide-activated BV2 microglia
      confirmed that MB treatment directly reduced IL-1beta and increased IL-10
      messenger ribonucleic acid in microglia. Last, functional recovery and depressive
      like behavior were assessed up to one week after TBI. MB intervention did not
      prevent TBI-induced reductions in body weight or motor coordination 1-7 d post
      injury. Nonetheless, MB attenuated the development of acute depressive-like
      behavior at 7 d post injury. Taken together, immediate intervention with MB was
      effective in reducing neuroinflammation and improving behavioral recovery after
      diffuse brain injury. Thus, MB intervention may reduce life-threatening
      complications of TBI, including edema and neuroinflammation, and protect against
      the development of neuropsychiatric complications.

PMID- 25070746
TI  - Attentional control in the attentional blink is modulated by odor.
AB  - Increasing evidence suggests that 'aromas have distinctive effects on the
      allocation of attention in space: Arousing olfactory fragrances (e.g.,
      peppermint) are supposed to induce a more focused state, and calming olfactory
      fragrances (e.g., lavender) a broader attentional state. Here, we investigate
      whether odors have similar effects on the allocation of attention in time.
      Participants performed the attentional blink (AB) task, known to produce a
      deficit in reporting the second of two target stimuli presented in close
      succession in a rapid sequence of distractors, while being exposed to either a
      peppermint or a lavender aroma. In two experiments using a between-subjects and a
      within-subjects design, respectively, we show that the two odors have specific
      effects on attentional control: As compared with the calming lavender aroma, the
      arousing peppermint condition yielded a larger AB. Our results demonstrate that
      attentional control is systematically modulated by factors that induce a more or
      a less distributed state of mind. 

PMID- 25070747
TI  - Isolation of adipose-derived stem cells by using a subfractionation culturing
      method.
AB  - OBJECTIVE: Adipose-derived stem cells (ASCs) isolated from subcutaneous adipose
      tissue have been tested in clinical trials. However, ASCs isolated by enzyme
      digestion and centrifugation are heterogeneous and exhibit wide variation in
      regenerative potential and clinical outcomes. Therefore, we developed a new
      method for isolating clonal ASCs (cASCs) that does not use enzyme digestion or
      centrifugation steps. RESEARCH DESIGN AND METHODS: In addition to cell surface
      markers and differentiation potential, we compared the mitogenic, paracrine and
      hair growth-promoting effects of ASCs isolated by the gradient centrifugation
      method (GCM) or by the new subfractionation culturing method (SCM). RESULTS: We
      selected three cASCs isolated by SCM that showed high rates of proliferation. The
      cell surface markers expressed by ASCs isolated by GCM or SCM were very similar,
      and SCM-isolated ASCs could potentially differentiate into different cell
      lineages. However, cASC lines exhibited better mitogenic and paracrine effects
      than ASCs isolated by GCM. The expression of Diras3, Myb, Cdca7, Mki67, Rrm2,
      Cdk1 and Ccna2, which may play a key role in cASC proliferation, was upregulated
      in cASCs. In addition, cASCs exhibited enhanced hair growth-promoting effects in
      dermal papilla cells and animal experiments. CONCLUSIONS: SCM generates a highly
      homogeneous population of ASCs via a simple and effective procedure that can be
      used in therapeutic settings.

PMID- 25070749
TI  - Strong resonance effect in a lossy medium-based optical cavity for angle robust
      spectrum filters.
AB  - Spectrum filters with a wide viewing angle exploiting strong resonance effects in
      lossy media are demonstrated. The designed filters show significantly improved
      color purity and the angle-robust characteristic can be preserved up to +/-65
      degrees  due to an interesting phase-cancellation effect. This strategy could
      provide new routes for numerous applications, such as image sensors and displays.

PMID- 25070748
TI  - Phloroglucinol induces apoptosis via apoptotic signaling pathways in HT-29 colon
      cancer cells.
AB  - Phloroglucinol is a polyphenolic compound that is used to treat and prevent
      several human diseases, as it exerts beneficial biological activities, including
      anti-oxidant, anti-inflammatory and anticancer properties. The aim of the present
      study was to investigate the effects of phloroglucinol on apoptotic signaling
      pathways in HT-29 colon cancer cells. The results indicated that phloroglucinol
      suppressed cell viability and induced apoptosis in HT-29 cells in a concentration
      dependent manner. Phloroglucinol treatment of HT-29 cells resulted in
      characteristic apoptosis-related changes: altered Bcl-2 family proteins,
      cytochrome c release, and activation of caspase-3 and caspase-8. This study also
      showed that proteins involved in apoptosis were stimulated by treatment with
      phloroglucinol. These findings demonstrated that phloroglucinol exerts anticancer
      activity in HT-29 colon cancer cells through induction of apoptosis. 

PMID- 25070750
TI  - How we approach an acquired thrombotic thrombocytopenic purpura patient.
AB  - Acquired thrombotic thrombocytopenic purpura (TTP) is a disease characterized by
      microangiopathic hemolytic anemia and thrombocytopenia, in addition to variable
      fever and neurologic and renal dysfunction, without an underlying cause. Recent
      advances in elucidating the pathophysiology of acquired TTP have led to new
      testing that we have incorporated into our current management of patients with
      suspected acquired TTP. Despite these developments, much of the treatment for
      acquired TTP beyond therapeutic plasma exchange (TPE) is based on low-quality
      evidence. Our group has a sustained interest in studying and optimizing the use
      of TPE, along with other concurrent therapies, in acquired TTP patients.
      Described herein is a summary of how our apheresis consult service approaches
      requests for TPE in patients with suspected acquired TTP. 

PMID- 25070751
TI  - Relatives' participation in everyday care in special care units for persons with
      dementia.
AB  - BACKGROUND: Research concerning relatives' participation in the everyday care
      related to persons living in special care units for persons with dementia is
      limited. RESEARCH QUESTIONS: To examine relatives' participation in their near
      one's everyday care, the level of burden experienced and important factors for
      participation, in this special context. DESIGN: The study had a cross-sectional
      design, and data collection was carried out by means of a study-specific
      questionnaire. PARTICIPANTS AND CONTEXT: A total of 233 relatives from 23
      different special care units participated. ETHICAL CONSIDERATION: The study was
      approved by the Norwegian Social Science Data Services. RESULTS: A great majority
      of relatives reported that they visited weekly and were the resident's
      spokesperson, but seldom really participated in decisions concerning their
      everyday care. Participation was seldom reported as a burden. DISCUSSION: This
      study indicated that relatives were able to make a difference to their near one's
      everyday life and ensure quality of care based on their biographical expertise,
      intimate knowledge about and emotional bond with the resident. Since knowing the
      resident is a prerequisite for providing individualised care that is in line with
      the resident's preferences, information concerning these issues is of utmost
      importance. CONCLUSION: This study prompts reflection about what it is to be a
      spokesperson and whether everyday care is neglected in this role. Even though
      relatives were satisfied with the care provided, half of them perceived their
      participation as crucial for the resident's well-being. This indicated that
      relatives were able to offer important extras due to their biographical
      expertise, intimate knowledge about and emotional bond with the resident. Good
      routines securing that written information about the residents' life history and
      preferences is available and used should be implemented in practice.

PMID- 25070752
TI  - TALEN-mediated somatic mutagenesis in murine models of cancer.
AB  - Cancer genome sequencing has identified numerous somatic mutations whose biologic
      relevance is uncertain. In this study, we used genome-editing tools to create and
      analyze targeted somatic mutations in murine models of liver cancer.
      Transcription activator-like effector nucleases (TALEN) were designed against
      beta-catenin (Ctnnb1) and adenomatous polyposis coli (Apc), two commonly mutated
      genes in hepatocellular carcinoma (HCC), to generate isogenic HCC cell lines.
      Both mutant cell lines exhibited evidence of Wnt pathway dysregulation. We asked
      whether these TALENs could create targeted somatic mutations after hydrodynamic
      transfection into mouse liver. TALENs targeting beta-catenin promoted endogenous
      HCC carrying the intended gain-of-function mutations. However, TALENs targeting
      Apc were not as efficient in inducing in vivo homozygous loss-of-function
      mutations. We hypothesized that hepatocyte polyploidy might be protective against
      TALEN-induced loss of heterozygosity, and indeed Apc gene editing was less
      efficient in tetraploid than in diploid hepatocytes. To increase efficiency, we
      administered adenoviral Apc TALENs and found that we could achieve a higher
      mutagenesis rate in vivo. Our results demonstrate that genome-editing tools can
      enable the in vivo study of cancer genes and faithfully recapitulate the mosaic
      nature of mutagenesis in mouse cancer models. Cancer Res; 74(18); 5311-21.
      (c)2014 AACR. 

PMID- 25070753
TI  - RPA inhibition increases replication stress and suppresses tumor growth.
AB  - The ATR/Chk1 pathway is a critical surveillance network that maintains genomic
      integrity during DNA replication by stabilizing the replication forks during
      normal replication to avoid replication stress. One of the many differences
      between normal cells and cancer cells is the amount of replication stress that
      occurs during replication. Cancer cells with activated oncogenes generate
      increased levels of replication stress. This creates an increased dependency on
      the ATR/Chk1 pathway in cancer cells and opens up an opportunity to
      preferentially kill cancer cells by inhibiting this pathway. In support of this
      idea, we have identified a small molecule termed HAMNO ((1Z)-1-[(2
      hydroxyanilino)methylidene]naphthalen-2-one), a novel protein interaction
      inhibitor of replication protein A (RPA), a protein involved in the ATR/Chk1
      pathway. HAMNO selectively binds the N-terminal domain of RPA70, effectively
      inhibiting critical RPA protein interactions that rely on this domain. HAMNO
      inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR.
      By itself, HAMNO treatment creates DNA replication stress in cancer cells that
      are already experiencing replication stress, but not in normal cells, and it acts
      synergistically with etoposide to kill cancer cells in vitro and slow tumor
      growth in vivo. Thus, HAMNO illustrates how RPA inhibitors represent candidate
      therapeutics for cancer treatment, providing disease selectivity in cancer cells
      by targeting their differential response to replication stress. Cancer Res;
      74(18); 5165-72. (c)2014 AACR. 

PMID- 25070754
TI  - The COMFORT behaviour scale detects clinically meaningful effects of analgesic
      and sedative treatment.
AB  - BACKGROUND: The COMFORT behaviour scale (COMFORT-B scale) is widely used in
      paediatric intensive care units to assess young children's pain and distress. It
      is also used to assess the impact of treatment interventions, but little is known
      on the scale's sensitivity to detect changes between before and after
      measurements following an intervention. This study explored the sensitivity to
      change of the COMFORT-B scale. METHODS: COMFORT-B scores, originally and
      prospectively collected as part of standard care, were retrieved from the digital
      patient data management system. We analysed scores obtained in 747 paired
      observations, i.e., before and after a pharmacological intervention in 180
      paediatric intensive care patients between September 2009 and September 2010.
      RESULTS: The mean scores before and after an intervention were 20.0 [standard
      deviation (SD) 3.7] and 14.1 (SD 4.7), respectively. Multilevel regression
      analysis showed a 6-point mean decline after an intervention (p < 0.0001). The
      magnitude of this decline was not statistically significantly related to number
      and type of interventions or time between assessments. In almost three-quarters
      of cases (74%), the COMFORT-B score dropped to below 17 after a pharmacological
      intervention, indicating good responsiveness. CONCLUSIONS: This is the first
      study demonstrating that the COMFORT-B scale detects treatment-related changes in
      pain or distress intensity. This implies that COMFORT-B assessments can
      effectively guide analgesic and sedation treatment in critically ill children.

PMID- 25070755
TI  - Prediction of the hemoglobin level in hemodialysis patients using machine
      learning techniques.
AB  - Patients who suffer from chronic renal failure (CRF) tend to suffer from an
      associated anemia as well. Therefore, it is essential to know the hemoglobin (Hb)
      levels in these patients. The aim of this paper is to predict the hemoglobin (Hb)
      value using a database of European hemodialysis patients provided by Fresenius
      Medical Care (FMC) for improving the treatment of this kind of patients. For the
      prediction of Hb, both analytical measurements and medication dosage of patients
      suffering from chronic renal failure (CRF) are used. Two kinds of models were
      trained, global and local models. In the case of local models, clustering
      techniques based on hierarchical approaches and the adaptive resonance theory
      (ART) were used as a first step, and then, a different predictor was used for
      each obtained cluster. Different global models have been applied to the dataset
      such as Linear Models, Artificial Neural Networks (ANNs), Support Vector Machines
      (SVM) and Regression Trees among others. Also a relevance analysis has been
      carried out for each predictor model, thus finding those features that are most
      relevant for the given prediction. 

PMID- 25070756
TI  - A low-cost real time virtual system for postural stability assessment at home.
AB  - BACKGROUND AND OBJECTIVE: The degeneration of the balance control system in the
      elderly and in many pathologies requires measuring the equilibrium conditions
      very often. In clinical practice, equilibrium control is commonly evaluated by
      using a force platform (stabilometric platform) in a clinical environment. In
      this paper, we demonstrate how a simple movement analysis system, based on a 3D
      video camera and a 3D real time model reconstruction of the human body, can be
      used to collect information usually recorded by a physical stabilometric
      platform. METHODS: The algorithm used to reconstruct the human body model as a
      set of spheres is described and discussed. Moreover, experimental measurements
      and comparisons with data collected by a physical stabilometric platform are also
      reported. The measurements were collected on a set of 6 healthy subjects to whom
      a change in equilibrium condition was stimulated by performing an equilibrium
      task. RESULTS: The experimental results showed that more than 95% of data
      collected by the proposed method were not significantly different from those
      collected by the classic platform, thus confirming the usefulness of the proposed
      system. CONCLUSIONS: The proposed virtual balance assessment system can be
      implemented at low cost (about 500$) and, for this reason, can be considered a
      home use medical device. On the contrary, astabilometric platform has a cost of
      about 10,000$ and requires periodical calibration. The proposed system does not
      require periodical calibration, as is necessary for stabilometric force
      platforms, and it is easy to use. In future, the proposed system with little
      integration can be used, besides being an emulator of a stabilometric platform,
      also to recognize and track, in real time, head, legs, arms and trunk, that is to
      collect information actually obtained by sophisticated optoelectronic systems.

PMID- 25070757
TI  - Open source EMR software: profiling, insights and hands-on analysis.
AB  - BACKGROUND: The use of open source software in health informatics is increasingly
      advocated by authors in the literature. Although there is no clear evidence of
      the superiority of the current open source applications in the healthcare field,
      the number of available open source applications online is growing and they are
      gaining greater prominence. This repertoire of open source options is of a great
      value for any future-planner interested in adopting an electronic medical/health
      record system, whether selecting an existent application or building a new one.
      The following questions arise. How do the available open source options compare
      to each other with respect to functionality, usability and security? Can an
      implementer of an open source application find sufficient support both as a user
      and as a developer, and to what extent? Does the available literature provide
      adequate answers to such questions? This review attempts to shed some light on
      these aspects. OBJECTIVE: The objective of this study is to provide more
      comprehensive guidance from an implementer perspective toward the available
      alternatives of open source healthcare software, particularly in the field of
      electronic medical/health records. METHODS: The design of this study is twofold.
      In the first part, we profile the published literature on a sample of existent
      and active open source software in the healthcare area. The purpose of this part
      is to provide a summary of the available guides and studies relative to the
      sampled systems, and to identify any gaps in the published literature with
      respect to our research questions. In the second part, we investigate those
      alternative systems relative to a set of metrics, by actually installing the
      software and reporting a hands-on experience of the installation process,
      usability, as well as other factors. RESULTS: The literature covers many aspects
      of open source software implementation and utilization in healthcare practice.
      Roughly, those aspects could be distilled into a basic taxonomy, making the
      literature landscape more perceivable. Nevertheless, the surveyed articles fall
      short of fulfilling the targeted objective of providing clear reference to
      potential implementers. The hands-on study contributed a more detailed
      comparative guide relative to our set of assessment measures. Overall, no system
      seems to satisfy an industry-standard measure, particularly in security and
      interoperability. The systems, as software applications, feel similar from a
      usability perspective and share a common set of functionality, though they vary
      considerably in community support and activity. CONCLUSION: More detailed
      analysis of popular open source software can benefit the potential implementers
      of electronic health/medical records systems. The number of examined systems and
      the measures by which to compare them vary across studies, but still rewarding
      insights start to emerge. Our work is one step toward that goal. Our overall
      conclusion is that open source options in the medical field are still far behind
      the highly acknowledged open source products in other domains, e.g. operating
      systems market share.

PMID- 25070759
TI  - Relationship between hip and core strength and frontal plane alignment during a
      single leg squat.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      frontal plane kinematics of the single leg squat and strength of the trunk and
      hip in females. PARTICIPANTS: Forty healthy females participated in this study.
      METHODS: An isometric "make" test using a dynamometer was used to assess peak
      force normalized to body weight for hip abduction, hip extension, hip external
      rotation, and a sidelying plank test. Two-dimensional software was used to
      analyze the frontal plane projection angle (FPPA) and pelvic angle during a
      single leg squat to 60 degrees . RESULTS: All 4 strength factors were
      significantly correlated with the FPPA, ranging from r = 0.396 to r = 0.466.
      During multiple regression analysis, hip abduction strength was the greatest
      predictor of the variation in FPPA at r(2) = 0.22, p = 0.002. Thus, hip abduction
      strength accounted for 22% of the variation in the FPPA during the single leg
      squat. The only strength factor demonstrating a significant correlation with the
      pelvic angle was hip extension strength (r = 0.550, p < 0.001). CONCLUSION:
      Clinicians should consider the role of the hip abductors, hip external rotators,
      hip extensors and core musculature on the impact on the FPPA during a single
      squat, with focus on the hip abductors.

PMID- 25070760
TI  - Foundations for value education in engineering: the Indian experience.
AB  - The objective of this paper is to discuss some of the foundational issues
      centering around the question of integrating education in human values with
      professional engineering education: its necessity and justification. The paper
      looks at the efforts in 'tuning' the technical education system in India to the
      national goals in the various phases of curriculum development. The contribution
      of the engineering profession in national development and India's self
      sufficiency is crucially linked with the institutionalization of expertise and
      the role of morality and responsibility. This linkage can be created through a
      proper understanding of the social role of the profession-what motivates the
      professionals and what makes professional life meaningful. Value education
      facilitates the process of moral maturity and the development of a 'holistic'
      mindset. This paper deals with the need to create such a mindset, the human
      values associated with it and gives examples of efforts to impart such education
      through 'action-oriented' programmes introduced in some institutes of engineering
      in India. 

PMID- 25070761
TI  - The many stories of my mother's death.

PMID- 25070762
TI  - ABO-incompatible kidney transplant recipients have a higher bleeding risk after
      antigen-specific immunoadsorption.
AB  - Pretransplant removal of antiblood group ABO antibodies is the cornerstone of all
      current ABO-incompatible (ABOi) transplantation programmes. In our protocol,
      plasmapheresis (PP) is performed with a plasmafilter followed by immunoadsorption
      (IA) of anti-ABO antibodies. The bleeding complications of this technique are not
      known. We analysed the data of all 65 consecutive ABOi kidney transplantations
      between March 2006 and October 2013 and compared these with matched 130 ABO
      compatible (ABOc) kidney transplantations. Cases differed from controls in the
      pre-operative regimen, which included IA-PP and rituximab, tacrolimus,
      mycophenolate mofetil, prednisone and immunoglobulines. Data on platelet count,
      blood loss and red blood cell (EC) transfusions during 48 h postoperatively were
      collected. ABOi patients received EC transfusions more frequently than controls
      (29% vs. 12%, P = 0.005). Intra-operative blood loss was higher (544 vs. 355 ml,
      P < 0.005) and they experienced more major bleeding (>=3 EC within 24 h, 15% vs.
      2%, P < 0.0005). Platelet count decreased by 28% after the pre-operative IA. In a
      multivariate model, only the number of pre-operative IAs was associated with the
      number of ECs given (OR per IA 1.9, P < 0.05). ABOi kidney transplant recipients
      have a high postoperative bleeding risk, correlating with the number of pre
      operative IA sessions performed. 

PMID- 25070763
TI  - Inhibitory effects of SKI3246, the rhizome extract of Atractylodes japonica, on
      visceral hypersensitivity in experimental irritable bowel syndrome rat models.
AB  - We evaluated the effect of SKI3246, the 50% ethanol extract of the rhizome of
      Atractylodes japonica, on visceral hypersensitivity, which is a major
      characteristic feature of IBS. We used various rat models of visceral
      hypersensitivity to assess the visceral pain responses to colorectal distension
      (CRD) in comparison with conventional IBS treatments. Oral administration of
      SKI3246 dose-dependently and significantly attenuated the abdominal withdrawal
      reflex (AWR) score in a model of acetic acid-induced visceral hypersensitivity.
      We also found that it reduced the number of abdominal contractions in response to
      CRD in a model of 2,4,6-trinitrobenzenesulfonic acid-induced visceral
      hypersensitivity, which was comparable to ramosetron or alosetron. Furthermore,
      treatment with SKI3246 also increased the pain threshold and abolished the
      elevated AWR scores to CRD in a rat model of neonatal maternal separation. We
      presumed that the modulation of the NK2 receptor is involved in the inhibitory
      activity of SKI3246 on the basis that it significantly inhibited the contraction
      of the distal colonic muscle induced by neurokinin A, the NK2 receptor agonist.
      The present results indicate that SKI3246 has the potential to be an effective
      therapeutic agent for IBS, especially insofar as it can relieve visceral
      hypersensitivity.

PMID- 25070764
TI  - Targeting components of epigenome by small molecules.
AB  - The diverse epigenetic modifications regulate the gene expression and determine
      the cellular identity. Pioneering work over the past decades has highlighted that
      these epigenetic regulations establish normal development but also contribute
      various diseases. Furthermore, the epigenetic priming events are considered as a
      key factor for efficient master transcription factor(s) mediated reprogramming
      process. With the advent of numerous small molecules that target specific enzymes
      or proteins involved in the epigenetic regulation of gene expression, the
      utilization of epigenetic targets is emerging as a valuable approach to cancer
      therapy and cellular reprogramming. Here, we briefly present the basic principles
      of epigenetic regulations and review the recent application of epigenetic
      targeting small molecules. 

PMID- 25070765
TI  - Transcription factors and glyoxylate cycle genes prominent in the transition of
      soybean cotyledons to the first functional leaves of the seedling.
AB  - During early seedling growth, the cotyledons transition from a storage tissue to
      become effectively the first leaf-like structures of the plant. In this
      programmed developmental process, they likely undergo a massive change in gene
      expression to redirect their metabolism and physiological processes. To define
      the developmental shifts in gene expression and begin to understand the gene
      regulatory networks that set this transition in motion, we carried out high
      throughput RNA sequencing of cotyledons from seven developmental stages of
      soybean seedlings. We identified 154 gene models with high expression exclusively
      in the early seedling stages. A significant number (about 25 %) of those genes
      with known annotations were involved in carbohydrate metabolism. A detailed
      examination of glyoxylate cycle genes revealed the upregulation of their
      expression in the early stages of development. A total of approximately 50 % of
      the highly expressed genes whose expression peaked in the mid-developmental
      stages encoded ribosomal family proteins. Our analysis also identified 219 gene
      models with high expression at late developmental stages. The majority of these
      genes are involved in photosynthesis, including photosystem I- and II-associated
      genes. Additionally, the advantage of RNA-Seq to detect genes expressed at low
      levels revealed approximately 460 transcription factors with notable expression
      in at least one stage of the developing soybean seedling. Relatively over
      represented transcription factor genes encode AP2, zinc finger, NAC, WRKY, and
      MYB families. These transcription factor genes may lead to the transcriptional
      reprogramming during the transition of seedling cotyledons from storage tissue to
      metabolically active organs that serve as the first functional leaves of the
      plant. 

PMID- 25070767
TI  - Spatially controlled graphitization of reduced graphene oxide films via a green
      mechanical approach.
AB  - An effective approach to fabricate micropatterned reduced graphene oxide sheets
      is explored on the basis of the pressure-assisted thermal graphitization as a
      concept of eco-friendly method. The high pressure can considerably reduce the
      graphitization temperature and substantially accelerate the kinetics of phase
      transformation of non-crystalline graphene domain, leading to enhance the degree
      of graphitization. 

PMID- 25070766
TI  - The association of metabolic syndrome and its factors with gallstone disease.
AB  - BACKGROUND: To investigate the association between metabolic syndrome, including
      its factors, and gallstone disease (GSD) in a Taiwanese population. METHODS: We
      conducted a cross-sectional study during 2011 ~ 2012. A total of 12050 subjects
      who completed a questionnaire and underwent physical examination, laboratory
      tests and abdominal ultrasonography formed the study population. RESULTS: The
      prevalences of metabolic syndrome and gallstone disease were 24.09% and 6.16%. In
      an age- and sex-adjusted logistic regression model, metabolic syndrome was
      associated with gallstone disease (OR = 1.61; P < 0.0001). Age, abdominal
      obesity, and lower high-density lipoprotein cholesterol were associated with
      gallstone disease after adjusting for other factors. Females had a higher odds
      ratio than males in waist circumference for GSD, whereas males had a lower odds
      ratio than females in HDL-C for GSD. CONCLUSIONS: The present study suggests that
      metabolic syndrome is related to gallstone disease. Waist circumference and high
      density lipoprotein cholesterol are all associated with GSD. Men and women may
      possibly have different priorities and strategies to reduce the burden of GSD.

PMID- 25070768
TI  - Cognitive impairment in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is characterised by repetitive cessation or
      reduction of airflow due to upper airway obstructions. These respiratory events
      lead to chronic sleep fragmentation and intermittent hypoxemia. Several studies
      have shown that OSA is associated with daytime sleepiness and cognitive
      dysfunctions, characterized by impairments of attention, episodic memory, working
      memory, and executive functions. This paper reviews the cognitive profile of
      adults with OSA and discusses the relative role of altered sleep and hypoxemia in
      the aetiology of these cognitive deficits. Markers of cognitive dysfunctions such
      as those measured with waking electroencephalography and neuroimaging are also
      presented. The effects of continuous positive airway pressure (CPAP) on cognitive
      functioning and the possibility of permanent brain damage associated with OSA are
      also discussed. Finally, this paper reviews the evidence suggesting that OSA is a
      risk factor for developing mild cognitive impairment and dementia in the aging
      population and stresses the importance of its early diagnosis and treatment. 

PMID- 25070769
TI  - Atmospheric chemistry of short-chain haloolefins: photochemical ozone creation
      potentials (POCPs), global warming potentials (GWPs), and ozone depletion
      potentials (ODPs).
AB  - Short-chain haloolefins are being introduced as replacements for saturated
      halocarbons. The unifying chemical feature of haloolefins is the presence of a CC
      double bond which causes the atmospheric lifetimes to be significantly shorter
      than for the analogous saturated compounds. We discuss the atmospheric lifetimes,
      photochemical ozone creation potentials (POCPs), global warming potentials
      (GWPs), and ozone depletion potentials (ODPs) of haloolefins. The commercially
      relevant short-chain haloolefins CF3CFCH2 (1234yf), trans-CF3CHCHF (1234ze(Z)),
      CF3CFCF2 (1216), cis-CF3CHCHCl (1233zd(Z)), and trans-CF3CHCHCl (1233zd(E)) have
      short atmospheric lifetimes (days to weeks), negligible POCPs, negligible GWPs,
      and ODPs which do not differ materially from zero. In the concentrations expected
      in the environment their atmospheric degradation products will have a negligible
      impact on ecosystems. CF3CFCH2 (1234yf), trans-CF3CHCHF (1234ze(Z)), CF3CFCF2
      (1216), cis-CF3CHCHCl (1233zd(Z)), and trans-CF3CHCHCl (1233zd(E)) are
      environmentally acceptable. 

PMID- 25070770
TI  - A systematic approach to the magnetic resonance imaging-based differential
      diagnosis of congenital Mullerian duct anomalies and their mimics.
AB  - Mullerian duct anomalies (MDAs) represent a wide spectrum of developmental
      abnormalities related to various gynecologic and obstetric complications,
      including primary amenorrhea, infertility, and endometriosis. The use of diverse
      imaging modalities, in conjunction with clinical information, provide important
      clues to the diagnosis of MDAs. Diagnostic imaging work-up for MDAs often begins
      with hysterosalpingography (HSG) and/or ultrasonography (US). Although HSG and/or
      US may suffice to detect the presence of a uterine abnormality, magnetic
      resonance (MR) imaging is generally needed to classify the abnormality into a
      specific MDA category. MR imaging has been gaining in popularity for use in
      evaluating MDAs, by virtue of its noninvasiveness, lack of ionizing radiation,
      and capability for multiplanar imaging and soft tissue characterization.
      Abnormalities in the external uterine fundal contour are readily recognized with
      MR imaging, allowing for clear differentiation between a fusion anomaly, such as
      a uterus didelphys or a bicornuate uterus, and a resorption anomaly, such as a
      septate uterus. Furthermore, MR imaging enables clear depiction of a rudimentary
      uterine horn in a unicornuate uterus. Accurate differential diagnosis of MDAs on
      the basis of their characteristic MR imaging findings is crucial, because the
      rates of gynecologic and obstetric complications vary considerably among MDAs.
      The diagnostic accuracy may be enhanced by adopting a systematic approach to MR
      imaging-based differential diagnosis. 

PMID- 25070771
TI  - Diffusion-weighted magnetic resonance imaging indicates the severity of acute
      pancreatitis.
AB  - PURPOSE: To test the use of diffusion-weighted magnetic resonance imaging (DW
      MRI) to differentiate between different degrees of severity of acute pancreatitis
      (AP). METHOD: Thirty-six patients who underwent DW-MRI and magnetic resonance
      cholangiopancreatography were divided into patients with mild AP (mAP, n = 15),
      patients with necrotizing AP (nAP, n = 8), and patients with a normal pancreas
      (nP, n = 15; controls). The pancreas was divided into head, body, and tail, and
      each segment was classified according to image features: pattern 1, normal;
      pattern 2, mild inflammation; and pattern 3, necrosis. Apparent diffusion
      coefficients (ADCs) were measured in each segment and correlated with clinical
      diagnoses. RESULTS: A total of 108 segments was assessed (three segments per
      patient). Segments classified as pattern 1 in the nP and mAP groups showed
      similar ADC values (P = 0.29). ADC values calculated for the pancreatic segments
      grouped according to the different image patterns (1-3) were significantly
      different (P < 0.001). Comparisons revealed significant differences in signal
      intensity between all three patterns (P < 0.05). CONCLUSIONS: DW-MRI was a
      compatible and safe image option to differentiate tissue image patterns in
      patients with mAP, nAP, and nP, mainly in those with contraindications to
      contrast-enhanced MRI (which is classically required for determining the presence
      of necrosis) or computed tomography. ADC measures allowed precise differentiation
      between patterns 1, 2, and 3.

PMID- 25070772
TI  - Tunneling hair syndrome: a description of a new entity.

PMID- 25070773
TI  - Annulation approach to doubly linked (A-type) oligocatechins: syntheses of (+)
      procyanidin A2 and (+)-cinnamtannin B1.
AB  - The first stereoselective syntheses of doubly linked (A-type) oligocatechins, (+)
      procyanidin A2 and (+)-cinnamtannin B1, have been achieved. Ethylenedioxy-bridged
      flavans served as excellent platforms, thus allowing annulation with nucleophilic
      catechin units in a stereoselective manner. An additional key was the new
      synthetic approach to selectively protected nucleophilic catechin, thus enabling
      regioselective construction of the key dioxabicyclo skeleton of the A-type
      oligocatechins.

PMID- 25070774
TI  - Comparison of donkey hemogram using the LaserCyte hematology analyzer, an
      impedance system, and a manual method.
AB  - BACKGROUND: Donkeys are becoming increasingly important worldwide; therefore a
      reliable and accurate method of diagnosing disease is necessary. Flow cytometry
      based hematologic analyzers are present in veterinary laboratories, but
      performance of LaserCyte has not been evaluated in donkeys. OBJECTIVES: The
      objective of the study was to compare the results of donkey blood obtained from
      the LaserCyte with impedance and manual methods. METHODS: Blood samples were
      collected from 84 healthy donkeys (1-20 years old) and measured with LaserCyte,
      Sysmex F-820 and manually. Agreement between methods was studied using Passing
      Bablok test and Bland-Altman plots. Influence of blood abnormalities found on
      blood smears on LaserCyte counts was examined using Mann-Whitney or Kruskal
      Wallis test. Intraassay precision was calculated. RESULTS: Hematologic variables
      obtained from the LaserCyte were significantly different from those obtained with
      impedance or manual methods; numerous values were flagged. Agreement between
      LaserCyte and manual method was poor for the majority of variables, but agreement
      between LaserCyte and impedance was only poor for HCT, MCH, and MCHC. LaserCyte
      had an intraassay precision < 10% for RBC and platelet variables, and > 10% for
      WBC variables. CONCLUSIONS: LaserCyte results were not interchangeable with
      results from other methods due to poor agreement. LaserCyte provided no
      additional hematologic variables or clinically relevant indices for donkey blood
      analysis. A large number of results were flagged, requiring the evaluation of
      blood smears. No benefits were found for the use of LaserCyte analyzer over the
      use of impedance or manual methods in this study. Specific software for LaserCyte
      for donkey blood would be beneficial.

PMID- 25070775
TI  - Chemoembolization via the left internal mammary artery supplying hepatocellular
      carcinoma.
AB  - PURPOSE: To present radiologic findings that show favorable tumor response after
      chemoembolization via the left internal mammary artery (LIMA). MATERIALS AND
      METHODS: Between October 2002 and April 2013, 57 patients with hepatocellular
      carcinoma (HCC) underwent 69 sessions of chemoembolization via the LIMA. Imaging
      findings including tumor size, location, and visibility of tumor-feeding artery
      on cross-sectional images were retrospectively reviewed in consensus by two
      radiologists. Tumor response after chemoembolization via the LIMA was assessed by
      the modified Response Evaluation Criteria in Solid Tumors on follow-up
      multidetector computed tomography in consensus. RESULTS: The mean tumor size
      supplied by the LIMA was 6.8 cm (range, 1.0-21.0 cm). HCCs supplied by the LIMA
      tended to be located in the subcapsular area including exophytic features (57 of
      57; 100%) and were more likely to be located in the left lobe of the liver (56 of
      57; 98%). HCCs supplied by the LIMA were more likely to be multiple or
      infiltrative (52 of 57; 91%) and marginally recurred (43 of 57; 75%). Feeding
      arteries of the LIMA were identified in a high percentage of cases (49 of 66;
      74%) on cross-sectional images obtained before embolization. Regarding tumor
      response, tumors that were newly developed or exclusively supplied by the LIMA
      showed better target tumor response (P = .011 and P < .0001, respectively). On
      multivariate analysis, tumors exclusively supplied by the LIMA showed
      significantly better target tumor response with odds ratio of 16.32. CONCLUSIONS:
      Chemoembolization via the LIMA has a favorable target tumor response when HCCs
      are exclusively supplied by the LIMA.

PMID- 25070776
TI  - Marine chemical ecology in benthic environments.
AB  - This review covers the recent marine chemical ecology literature for benthic
      bacteria and cyanobacteria, macroalgae, sponges, cnidarians, molluscs, other
      benthic invertebrates, and fish.

PMID- 25070777
TI  - MicroRNAs: non coding pleiotropic factors in development, cancer prevention and
      treatment.
AB  - One of the most important advance obtained from transcriptome analysis in recent
      years is the discovery of a series of noncoding RNA (ncRNA) families, with
      regulatory roles in several biological processes, that are actively transcribed
      from the genome of many organisms. Among them microRNAs (miRNAs) are small
      regulatory, single-stranded, RNA molecules (19-25 nucleotides in length) that are
      generated from hairpin primary transcripts [1]. In the cytoplasm, the mature
      miRNA molecule, through a limited base-pairing complementary sequences
      interaction, destabilizes or blocks the translation of their phylogenetically
      conserved target mRNAs transcripts [2]. Following the identification of a
      functional miRNAs pathway in C. elegans, miRNAs contribution to development, cell
      fate determination and physiological tissue homeostasis in mammals has rapidly
      emerged [3]. MiRNAs exhibit a developmental stage- and tissue-specific expression
      pattern and are present in complex regulatory circuits to regulate stem cells
      function, tissue differentiation and maintenance of cell identity during
      embryogenesis and adult life [4]. Recently, the deregulation of miRNAs expression
      and activity has been correlated with the pathogenesis of various human diseases
      and cancer. In cancer, the loss of tumour suppressive miRNAs enhances the
      expression of target oncogenes, whereas increased expression of oncogenic miRNAs
      can repress target tumour suppressor genes [5, 6]. This new wealth of knowledge
      points to miRNAs as being novel cancer genes and biomarkers relevant to the
      pathogenesis, diagnosis and prognosis of disease that may be useful in the
      management of human cancer. Moreover, the localization of non-random chromosomal
      abnormalities and other types of genetic alterations at miRNA genomic regions
      observed in several types of cancer cells underline the contribution of the
      deregulation of miRNAs expression to malignancy processes [7]. Advances in
      expression technologies have facilitated the high-throughput analysis of small
      RNAs, identifying novel miRNAs and showing that these genes may be aberrantly
      expressed in various human tumors [8]. Hence, a new molecular taxonomy of human
      cancers based on miRNAs expression profiling has been proposed. Indeed, it was
      recently found that miRNAs profiles are more informative than messenger RNA
      profiles and could classify poorly differentiated tumors since they better
      reflect the developmental lineage and differentiation state of cancer. Different
      wide screening approaches performed to establish miRNAs expression profiles
      showed a unique miRNAs signature, relevant to the pathogenesis, diagnosis and
      prognosis of disease that may be useful in the management of human cancer.
      Summarizing, miRNAs expression and regulation are emerging in several normal and
      pathological processes ranging from the control of embryonic stem cell commitment
      to the deregulation of cell fate determination and the molecular pathogenesis of
      human cancer. The aim of this issue is to review the functional roles of microRNA
      pathways in the establishment and progression of human diseases with a particular
      attention to the identification of miRNAs signatures as innovative cancer
      biomarkers for the management and prevention of human cancers.

PMID- 25070778
TI  - Lifestyle Factors and MicroRNAs: A New Paradigm in Cancer Chemoprevention.
AB  - MicroRNAs (miRNAs) are characterized as small RNA molecules that modulate gene
      transcription in a posttranslational manner. Functionally, miRNAs play important
      roles in a diverse number of biological processes, including cell development,
      differentiation, proliferation, and apoptosis. Consequently, changes in the
      expression pattern of miRNAs have been associated with multiple human
      pathologies, including cancer. Based on these alterations, distinct miRNAs can be
      utilized as markers for cancer risk evaluation or used in tumour detection.
      Recent evidence has indicated that lifestyle factors, such as nutrition, physical
      activity, and glycemic control provide health benefits through regulation of
      miRNA expression. In this review, we provide a concise overview of miRNA
      regulation, biosynthesis, and their expression patterns in normal and malignant
      tissue. We then summarize the emerging knowledge of how lifestyle factors,
      including nutrients, exercise, and hypoglycemic agents modify miRNAs and are
      involved in cancer prevention. Finally, we conclude by providing recommendation
      for future investigations into novel agents that can modulate miRNAs and act as
      chemotherapeutic agents against cancer.

PMID- 25070779
TI  - Non coding RNA in muscle differentiation and disease.
AB  - Non coding RNAs have provided in the last decades a very exciting research field
      with the discovery that a largely unexplored fraction of our genome encodes for
      RNA without protein coding activity. Here we revise the current knowledge of how
      non coding RNAs impact on muscle differentiation and homeostasis in normal and
      disease conditions and how they can provide powerful tools for therapeutic
      interventions and disease diagnosis. Moreover, we discuss new insights into
      additional mechanisms of post-transcriptional regulation involving a new class of
      long non coding RNAs shown to impact on the distribution of microRNA molecules on
      their mRNA targets.

PMID- 25070780
TI  - MicroRNAs as cancer biomarkers.
AB  - MicroRNAs (miRNAs) are attractive, short, non-coding RNAs widely studied for
      their fundamental roles in tissue homeostasis, cell proliferation, and
      dysregulation in cancer. A vast majority of investigations and technical
      improvements have focused on miRNAs' tumor-specific expression patterns, which
      provide novel molecular biomarkers for cancer detection and targeted therapies.
      In this review, we focus on recent achievements in biomarker validation and
      potential for cancer treatment, with special trend in non-invasive strategies to
      evaluate miRNAs, especially for diagnostic and prognostic applications. We
      further include a large compilation of PubMed data regarding microRNAs reported
      as diagnostic or prognostic cancer biomarkers in at least three studies.

PMID- 25070781
TI  - microRNA-203: Tumor Suppression and Beyond.
AB  - The involvement of microRNAs in human cancer is now well established. A few
      miRNAs function as oncogenes and many others display tumor suppressor activities.
      Several studies in the past few years have highlighted and reinforced a role for
      miR-203 as a tumor suppressor microRNA. This collection of in vitro studies give
      an initial and stimulating look into the many different means by which miR-203
      can inhibit the various pathways involved in cell transformation and metastasis.
      Of special relevance is the ability of miR-203 to prevent proliferation of
      progenitor cells as well the epithelial-to-mesenchymal transition frequently
      associated with cancer progression and metastasis. Further more, the breadth of
      cancer types examined in these studies implicates miR-203 as a potential tumor
      suppressor gene whose re-expression or re-introduction into malignant cells
      could, by nature of its inherent pleiotropic effects as a miRNA, represent an
      important therapeutic tool used to combat a multitude of human cancers.

PMID- 25070782
TI  - The Lilliputians and the Giant: An Emerging Oncogenic microRNA Network that
      Suppresses the PTEN Tumor Suppressor In Vivo.
AB  - MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that
      function via transcript degradation or translational inhibition, depending on the
      degree of complementarity with their target transcripts. They often exhibit
      temporal, spatial and developmental-stage specific expression, and have been
      found to be frequently dysregulated in multiple human diseases including various
      cancers. Numerous experimental and bioinformatic approaches have identified
      miRNAs that control cancer initiation and progression by directly targeting key
      oncogenes or tumor suppressors. PTEN (phosphatase and tensin homolog deleted on
      chromosome 10) is one of the most frequently disrupted tumor suppressor genes in
      multiple human cancers. PTEN is particularly susceptible to miRNA regulation as
      subtle changes in its dose have been shown to have a profound effect on
      tumorigenesis in vivo. Here we will review emerging evidence describing a vast
      layer of miRNA-mediated PTEN regulation, with a specific focus on their function
      in animal models in vivo, therapeutic implications, and directions for future
      research.

PMID- 25070784
TI  - Mirware: A MiRNA-mRNA Warehouse for Inference on Their Coordination.
AB  - Cancer is a multifactorial disease the study and analysis of which naturally
      require the integration of disciplines, and the fusion of omics and clinical
      evidence. Each informative layer linked to such combined evidence involves a
      particular type of complexity, in part technology-driven and in part patient
      dependent. Therefore, due to data dimensionality and heterogeneity the task for
      computational scientists is very challenging as it refers to data assimilation,
      mining and inference. Cancer-associated mechanisms refer to complex entities such
      as transcription factors and microRNA the influence of which is exerted over many
      distinct mRNA targets involved in key biological processes, both normal and
      altered ones. This work aims to propose an open source tool allowing inference on
      microRNA-target coordination involving cancer-induced dysregulation. By
      introducing Mirware, a novel warehouse of genes is provided to specifically and
      uniquely build a cancer repository based on publicly available data from Array
      Express, and populated by importing from Tarbase and Mirbase all the known
      associations between microRNAs and target genes. Coordination can be assessed by
      merging profiling from gene co-expression measurements and clinical evidence
      integrated to them. Data have been organized by tissue, such that microRNA-mRNA
      association matrices can be built based on both experimental and predicted data,
      thus promising to offer a contribution to build a knowledge base clarifying
      cancer regulation mechanisms.

PMID- 25070785
TI  - Prognostic value of one-year course of symptoms of anxiety and depression in
      patients with coronary heart disease: Role of physical activity and unmet medical
      need.
AB  - INTRODUCTION: Symptoms of depression and anxiety contribute to determining
      prognosis of patients with coronary heart disease. We evaluated the association
      of the one-year course of symptoms of anxiety and depressive symptoms with fatal
      and non-fatal cardiovascular disease-events during 10-year follow-up and assessed
      the utilization of anti-depressant and psycholeptic medication. METHODS:
      Prospective cohort study in coronary heart disease patients aged 30-70 years with
      stable coronary heart disease. Symptoms of anxiety and depression were evaluated
      at baseline and follow-up using the Hospital Anxiety and Depression Scale.
      Associations with fatal and non-fatal cardiovascular disease events were
      determined by a Cox-proportional hazards model. RESULTS: Nine hundred and ninety
      six patients were included in this study. Of the 862 patients with a normal
      depression symptom score at baseline 10.3% had an increased score at one-year
      follow-up. Of those with an elevated symptom score at baseline, 62.7% still had
      an elevated score after one year. During follow-up (median 8.9 years) fatal and
      non-fatal cardiovascular disease events were observed in 152 patients. One year
      course of depressive symptoms was associated with cardiovascular disease events
      during follow-up (p-value for trend 0.029); for example, patients with an
      increase of depressive symptoms had a hazard ratio of 1.93 (95% confidence
      interval 1.08-3.34) compared with patients with a normal score at baseline as
      well as at one-year follow-up. However, if physical activity was considered as a
      covariate, the HRs attenuated and the association was no longer statistically
      significant. The utilization of anti-depressant medication in the overall
      population was low (overall 2%). CONCLUSIONS: The study supports a role of the
      one year course of symptoms of depression for long-term prognosis of patients
      with known coronary heart disease, which might be partly mediated by lack of
      physical activity.

PMID- 25070783
TI  - MicroRNA and HER2-overexpressing cancer.
AB  - The discovery of microRNAs (miRNAs) has opened up new avenues for studying cancer
      at the molecular level, featuring a post-genomic era of biomedical research.
      These non-coding regulatory RNA molecules of ~22 nucleotides have emerged as
      important cancer biomarkers, effectors, and targets. In this review, we focus on
      the dysregulated biogenesis and function of miRNAs in cancers with an
      overexpression of the proto-oncogene HER2. Many of the studies reviewed here were
      carried out in breast cancer, where HER2 overexpression has been extensively
      studied and HER2-targeted therapy practiced for more than a decade. MiRNA
      signatures that can be used to classify tumors with different HER2 status have
      been reported but little consensus can be established among various studies,
      emphasizing the needs for additional well-controlled profiling approaches and
      meta-analyses in large and well-balanced patient cohorts. We further discuss
      three aspects of microRNA dysregulation in or contribution to HER2-associated
      malignancies or therapies: (a) miRNAs that are up- or down-regulated by HER2 and
      mediate the downstream signaling of HER2; (b) miRNAs that suppress the expression
      of HER2 or a factor in HER2 receptor complexes, such as HER3; and (c) miRNAs that
      affect responses to anti-HER2 therapies. The regulatory mechanisms are elaborated
      using mainly examples of miR- 205, miR-125, and miR-21. Understanding the
      regulation and function of miRNAs in HER2-overexpressing tumors shall shed new
      light on the pathogenic mechanisms of microRNAs and the HER2 proto-oncogene in
      cancer, as well as on individualized or combinatorial anti-HER2 therapies.

PMID- 25070786
TI  - The relationship between umbilical cord length and chronic rheumatic heart
      disease: a prospective cohort study.
AB  - BACKGROUND: One previous, preliminary study reported that the length of the
      umbilical cord at birth is related to the risk of developing chronic rheumatic
      heart disease in later life. We sought to replicate this finding. DESIGN:
      Prospective, population-based birth cohort. METHODS: We traced 11,580 individuals
      born between 1915 and 1929 in Uppsala, Sweden. We identified cases with a main or
      secondary diagnosis of chronic rheumatic heart disease in the Swedish national
      inpatient, outpatient or death registers. Archived obstetric records provided
      data on umbilical cord length, gestational age, birthweight and placental weight.
      RESULTS: There were 136 patients with chronic rheumatic heart disease (72 men and
      64 women) with a mean age at first hospital admission of 68 years (range 36-92).
      There was evidence of a positive association between umbilical cord length and
      risk of subsequent chronic rheumatic heart disease. The overall hazard ratio in
      the Swedish study (1.13, 95% confidence interval 1.01 to 1.27) was similar to
      that of the previous study, with some suggestion of larger effect in men than in
      women. No other birth characteristics were predictive except for weak evidence of
      a protective effect of higher birthweight in men. CONCLUSIONS: People with longer
      umbilical cords at birth are more likely to develop chronic rheumatic heart
      disease in later life. As longer umbilical cords have more spiral arteries and a
      higher vascular resistance, we hypothesize that the increased pressure load on
      the heart leads to changes in endothelial biology and increased vulnerability to
      the autoimmune process initiated by infection with beta-haemolytic streptococci.

PMID- 25070787
TI  - Obese children and adolescents need increased gastric volumes in order to
      perceive satiety.
AB  - OBJECTIVE: In order to develop effective weight management strategies, it is
      important to identify factors that influence energy intake. Portion size has been
      discussed as one such factor. To date, most studies focusing on the relationship
      between portion size, energy intake, and weight have analyzed questionnaire data
      and 24-h records. In this study, we assessed the onset of satiety using the water
      load test in normal-weight and obese children and adolescents. METHODS: 60 obese
      and 27 normal-weight children and adolescents aged between 9 and 17 years
      participated in the water load test which involved drinking water for 3 min or
      until feeling full. The amount of water consumed was recorded. RESULTS: Obese
      children and adolescents drank 20% more water until the onset of satiety when
      compared with normal-weight participants (478 +/- 222 ml vs. 385 +/- 115 ml, P <
      0.05). CONCLUSIONS: Obese children and adolescents need to ingest greater volumes
      to feel full which may predispose toward the consumption of larger portion sizes.
      This may easily lead to overeating if predominantly energy-dense foods are
      consumed. A reduction in energy-dense foods in the diet of obese children and
      adolescents appears to be a necessary strategy for managing body weight.

PMID- 25070788
TI  - Low back pain in children and adolescents: a systematic review and meta-analysis
      evaluating the effectiveness of conservative interventions.
AB  - PURPOSE: To identify and evaluate the effectiveness of conservative treatment
      approaches used in children and adolescents to manage and prevent low back pain
      (LBP). METHODS: Five electronic databases and the reference lists of systematic
      reviews were searched for relevant studies. Randomised controlled trials (RCTs)
      were considered eligible for inclusion if they enrolled a sample of children or
      adolescents (<18 years old) and evaluated the effectiveness of any conservative
      intervention to treat or prevent LBP. Two authors independently screened search
      results, extracted data, assessed risk of bias using the PEDro scale, and rated
      the quality of evidence using the GRADE criteria. RESULTS: Four RCTs on
      intervention and eleven RCTs on prevention of LBP were included. All included
      studies had a high risk of bias scoring <=7 on the PEDro scale. For the treatment
      of LBP, a supervised exercise program compared to no treatment improved the
      average pain intensity over the past month by 2.9 points (95 % CI 1.6-4.1)
      measured by a 0-10 scale (2 studies; n = 125). For the prevention of LBP, there
      was moderate quality evidence to suggest back education and promotion programs
      are not effective in reducing LBP prevalence in children and adolescents.
      CONCLUSIONS: While exercise interventions appear to be promising to treat LBP in
      children and adolescents, there is a dearth of research data relevant to
      paediatric populations. Future studies conducted in children and adolescents with
      LBP should incorporate what has been learnt from adult LBP research and be of
      rigorous methodological quality.

PMID- 25070790
TI  - Spondylolysis and spina bifida occulta in pediatric patients: prevalence study
      using computed tomography as a screening method.
AB  - PURPOSE: The prevalence of spondylolysis reported from radiograph-based studies
      has been questioned in recent computed tomography (CT)-based studies in adults;
      however, no new data are available in pediatric patients. Spina bifida occulta
      (SBO), which has been associated to spondylolysis, may be increasing its
      prevalence, according to recent studies in adults in the last decades, but
      without new data in pediatric patients. We aimed to determine the prevalence of
      spondylolysis and SBO in pediatric patients using abdomen and pelvis CT as a
      screening tool. METHODS: We studied 228 patients 4-15 years old (107 males), who
      were evaluated with abdomen and pelvis CT scans for reasons not related to the
      spine. The entire lumbo-sacral spine was evaluated to detect the presence of
      spondylolysis and SBO. We compared the prevalence of spondylolysis in patients
      with and without SBO. A logistic regression analysis was performed to determine
      the effect of age and sex as independent predictors of spondylolysis and SBO.
      RESULTS: The prevalence of spondylolysis was 3.5 % (1.1-5.9 %); 2/8 patients
      presented with olisthesis, both with grade I slip. The prevalence of SBO was 41.2
      % (34.8-59.2 %) (94 patients). Spondylolysis was not more frequent in patients
      with SBO than in patients without SBO. Male sex and decreasing age independently
      predicted the presence of SBO, but not of spondylolysis. CONCLUSION: We observed
      a 3.5 % prevalence of spondylolysis and a 41.2 % prevalence of SBO. SBO was
      significantly more frequent in males and younger patients.

PMID- 25070789
TI  - Heritability of spinal curvature and its relationship to disc degeneration and
      bone mineral density in female adult twins.
AB  - PURPOSE: To determine the heritability of spine curve using plain radiographs and
      to identify risk factors for spine curvature including age, body mass index,
      smoking, bone mineral density (BMD), and lumbar disc degeneration (LDD). METHODS:
      A classical twin study of 110 MZ and 136 DZ adult female twins. Demographic and
      clinical information obtained from long spine radiographs, lumbar spine
      degeneration on spine MR scan, and BMD assessed by DEXA at hip and lumbar spine
      were included in multiple logistic regression models to determine risk factors
      for spine curvature. RESULTS: Heritability estimates ranged between 41 (19-59) %
      for pelvic incidence to 61 (46-72) % for thoracic kyphosis; with lumbar lordosis
      and cervical lordosis having 59 (42-71) % and 43 (23-59) % heritability,
      respectively. For each spine curve, the model showing the best fit contained
      additive genetic and shared environmental components with no contribution from
      the unique environment. Significant risk factors for increased thoracic kyphosis
      were lumbar spine BMD, age, and cervical lordosis; for pelvic incidence were
      lumbar spine BMD and lumbar lordosis; for lumbar lordosis were cervical lordosis,
      pelvic incidence and LDD; and age alone predicted cervical lordosis (p = 0.001).
      CONCLUSION: In this sample of middle-aged and elderly women, there were
      significant genetic influences on all spine curves but particularly thoracic
      kyphosis and lumbar lordosis. The strongest predictor for lumbar lordosis was LDD
      (p < 0.0001) which is itself genetically determined in part. For thoracic
      kyphosis, BMD was strongly associated and remained so (for lumbar BMD) with the
      inclusion of age, showing BMD to be an independent risk factor. This work
      highlights the genetic factors influencing normal spine curvature in women.

PMID- 25070791
TI  - Potential role of F18 FDG PET-CT as an imaging biomarker for the noninvasive
      evaluation in uncomplicated skeletal tuberculosis: a prospective clinical
      observational study.
AB  - PURPOSE: This is a prospective non-randomized observation study done on 33
      patients with uncomplicated spinal tuberculosis to observe the imaging
      characteristics on sequential F-18 FDG PET CT scans. METHODS: 33 consecutive
      patients with pathologically proven spinal tuberculosis underwent a baseline
      contrast-enhanced whole body FDG PET scan before initiation of antitubercular
      therapy, 6 and 12 months and at 18 months or the end of antitubercular therapy.
      RESULT: The baseline peak SUVmax of lesions in our 33 cases had values ranging
      from 5.9 to 30.3 (mean 14.8). 63.6 % patients had clinically occult non
      contiguous multifocal skeletal involvement at the time of the baseline whole body
      PET CT scanning. The mean change in SUVmax at various time points was highly
      significant (p value < 0.001). CONCLUSION: SUVmax can be taken as a reliable
      marker for serial quantification of metabolic activity in spinal tuberculosis.
      This may translate into a potential role for FDG as an imaging biomarker for
      noninvasive response evaluation in skeletal tuberculosis.

PMID- 25070792
TI  - Free-hand placement of occipital condyle screws: a cadaveric study.
AB  - PURPOSE: Cranio-vertebral junction fixation is challenging due to the complex
      topographical anatomy and the presence of important anatomical structures. There
      are several limitations to the traditional occipital squama fixation methods. The
      purpose of this work is to assess the safety and feasibility of a new optimum
      trajectory of occipital condyle (OC) screws for occipitocervical fixation via a
      free-hand technique. METHODS: Eight different parameters of OC morphology were
      studied in fifty adult skulls. Free-hand placement of OC screws was performed in
      five cadavers using 3.5-mm titanium polyaxial screws and a 3-mm rod construct (C0
      C1-C2). Postoperative computed tomography was performed to determine the success
      of the screw placement and their angulation, length and effect on hypoglossal
      canal volume. RESULTS: The average length, width and height of the OC were 24.2
      +/- 3.6, 14.2 +/- 1.9, and 10.7 +/- 2 mm, respectively. The average medio
      lateral, hypoglossal canal and atlanto-occipital joint angles were 38.8 degrees 
      medially +/-5 degrees , 7.4 degrees  rostrally +/-1.9 degrees  and 23.4 degrees 
      caudally +/-3.5 degrees , respectively. The ten screws were successfully inserted
      using a free-hand technique with bicortical purchase. There was no vertebral
      artery injury or breach of the hypoglossal canal in any specimen. The average
      screw length was 22.2 +/- 3.9 mm. The average medio-lateral angle was 30 degrees 
      medially +/-6.7 degrees . The average cranio-caudal angle was 4 degrees  caudally
      +/-6.2 degrees . CONCLUSIONS: The free-hand technique of OC screw placement is a
      safe and viable option for occipitocervical fixation and may be a preferred
      alternative in selected cases. However, further studies are needed to compare its
      safety and reliability to other more established methods.

PMID- 25070793
TI  - Mortality attributable to rheumatic heart disease in the Kimberley: a data
      linkage approach.
AB  - BACKGROUND: Acute rheumatic fever (ARF) and its sequelae, rheumatic heart disease
      (RHD) are now uncommon in the general Australian population. However, these
      preventable and treatable diseases continue to affect Aboriginal Australians
      disproportionately, especially in remote communities. In the Kimberley region of
      Western Australia (WA), the prevalence of RHD is approximately 1% among
      Aboriginal residents. Yet an accurate and comprehensive picture of RHD-related
      mortality is lacking. AIM: This study aims to determine the mortality burden
      attributable to ARF and RHD in the Kimberley using linked hospitalisation and
      death registry data. METHODS: A retrospective cohort study was undertaken
      comprising all Kimberley residents with a WA hospital admission for ARF or RHD
      between 1970 and 2010, linked with the WA Death Register. We manually classified
      RHD-attributable deaths ('definite' or 'probable') to determine mortality burden.
      Hospitalisation prior to death, including valvular surgery was also ascertained.
      RESULTS: There were 35 RHD-attributable deaths in the Kimberley between 1990 and
      2010, with 94% occurring in Aboriginal people. Their median age of death was 40
      years. The age-standardised RHD annual death rate was 15.6 per 100 000 with a
      total of 1100 premature years of life lost before age of 75 within this group.
      Conventional International Classification of Diseases-generated mortality data
      underestimated mortality burden. CONCLUSION: RHD remains a significant cause of
      premature mortality for Aboriginal people in the Kimberley, with mortality rates
      unmatched in the general Australian population since the first half of the 20th
      century. Efforts to reduce progression of this disease through RHD Register and
      Control Programs are crucial alongside action to address underlying socioeconomic
      and environmental inequities.

PMID- 25070794
TI  - An investigation into the stability of microemulsions in electrophoresis.
AB  - A typical oil-in-water microemulsion (ME) was applied for the capillary
      electrophoretic separation of nonsteroidal anti-inflammatory drugs (NSAIDs). As
      the high-pH ME was introduced into the capillary and a voltage was applied, we
      observed an unusual phenomenon during the preconditioning process: a sharp
      inflection point occurred at 56.2 min ( +/- 4.8%) (N = 15). Both before (region
      A) and after (region B) that point, a steady state was observed. Highly
      reproducible results were obtained for this event. Two different absorbance
      patterns were observed for the hydrostatic injection of either freshly prepared
      ME or ME collected from the outlet of the capillary column during the steady
      state of region B. The latter had an inflection point at approximately 9 min,
      whereas the former had a constant absorbance over the entire range. To further
      characterize this property, regions A and B were used for the separation of
      NSAIDs. The results showed that both the detection limit and the reproducibility
      of the separation were superior in region B. For deep insight into the stability
      of the ME in an electric field, the effects of the oil, cosurfactant, pH, and
      voltage were systematically investigated in the neat ME. From our findings, it
      can be concluded that the inflection time might be the migration time of the ME
      in an electric field, and it might actually be the result of equilibration.
      Moreover, the existence of many unexpected phenomena seems to be the result of a
      change in the properties of ME droplet in an electric field.

PMID- 25070795
TI  - Regulatory codewords.

PMID- 25070796
TI  - miR-212 and miR-132 are dispensable for mouse mammary gland development.

PMID- 25070797
TI  - miR-212 and miR-132 are dispensable for mouse mammary gland development.

PMID- 25070798
TI  - From genomics to diagnostics of esophageal adenocarcinoma.

PMID- 25070799
TI  - Towards sequence-based genomic selection of cattle.

PMID- 25070800
TI  - Fingerprints of Epstein-Barr virus in nasopharyngeal carcinoma.

PMID- 25070806
TI  - Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by
      human trophoblast.
AB  - PROBLEM: Women with antiphospholipid syndrome (APS) are at increased risk of
      recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies
      (aPL) directly alter trophoblast function. Treatment with low molecular weight
      heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH
      stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with
      preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia,
      this study sought to determine the effect of vitamin D on trophoblast function in
      the setting of aPL and LMWH. METHOD OF STUDY: A human first trimester trophoblast
      cell line (HTR8) and primary trophoblast cultures were treated with or without
      aPL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion
      of inflammatory cytokines and angiogenic factors were measured by ELISA. RESULTS:
      Vitamin D alone or in combination with LMWH attenuated the aPL-induced
      trophoblast inflammatory response in the HTR8 cells and primary cultures. While
      vitamin D did not have any impact on aPL-mediated modulation of angiogenic
      factors in the primary trophoblast, it significantly inhibited LMWH-induced sFlt
      1 release. CONCLUSION: LMWH in combination with vitamin D may be more beneficial
      than single-agent therapy by preventing aPL-induced trophoblast inflammation and
      reversing LMWH-induced sFlt-1 secretion.

PMID- 25070808
TI  - High frequency of DQB1*05 and absolute absence of DRB1*13 in muscle-specific
      tyrosine kinase positive myasthenia gravis.
AB  - BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disease but
      certain genetic factors predispose its development. Since susceptibility to
      different forms of MG is linked to a number of allelic variants, the aim of this
      study was to explore the human leukocyte antigen (HLA) profile of our patients
      with muscle-specific tyrosine kinase (MuSK) MG. METHODS: Human leukocyte antigen
      (HLA) typing was performed in our cohort of 31 MuSK MG patients available for the
      study. The allele groups of DRB1* and DQB1* loci were typed with sequence
      specific oligonucleotide probes and high resolution typing for DQB1* was
      performed using sequence-specific primers. HLA frequencies were compared with
      unrelated healthy bone marrow donors. RESULTS: Significant association of MuSK MG
      with alleles DRB1*14 [odds ratio (OR) 3.8], DRB1*16 (OR 3.3) (P < 0.01) and
      DQB1*05 (OR 2.2) (P < 0.05) was found. In our patients the most frequent DQB1*
      allele was DQB1*05:02. An absolute absence of DRB1*13 in our cohort of MuSK MG
      patients was also found, whilst this allele was present in 25% (495/1992) of
      control subjects (OR 0) (P < 0.01). The HLA DRB1*16-DQB1*05 (OR 2.9) haplotype
      was found to be associated with MuSK MG (P < 0.05). CONCLUSIONS: The strong
      association of MuSK MG with DQB1*05 alleles observed in patient series from other
      countries was confirmed. The novel finding in our cohort of MuSK MG patients was
      the absolute absence of DRB1*13 allele, which might have a protective role in the
      development of MuSK MG, at least in our population.

PMID- 25070807
TI  - A type VI secretion-related pathway in Bacteroidetes mediates interbacterial
      antagonism.
AB  - Bacteroidetes are a phylum of Gram-negative bacteria abundant in mammalian
      associated polymicrobial communities, where they impact digestion, immunity, and
      resistance to infection. Despite the extensive competition at high cell density
      that occurs in these settings, cell contact-dependent mechanisms of
      interbacterial antagonism, such as the type VI secretion system (T6SS), have not
      been defined in this group of organisms. Herein we report the bioinformatic and
      functional characterization of a T6SS-like pathway in diverse Bacteroidetes.
      Using prominent human gut commensal and soil-associated species, we demonstrate
      that these systems localize dynamically within the cell, export antibacterial
      proteins, and target competitor bacteria. The Bacteroidetes system is a distinct
      pathway with marked differences in gene content and high evolutionary divergence
      from the canonical T6S pathway. Our findings offer a potential molecular
      explanation for the abundance of Bacteroidetes in polymicrobial environments, the
      observed stability of Bacteroidetes in healthy humans, and the barrier presented
      by the microbiota against pathogens. 

PMID- 25070810
TI  - CHARGE syndrome: an overview on dental and maxillofacial features.
AB  - OBJECTIVES: CHARGE is an acronym referring to the aspects of this rare syndromic
      condition. Patients with CHARGE association are today considered as subjects
      lacking in pathognomonic dental alterations. The present study is aimed at adding
      to the body of evidence of the cases reported in literature and the continuous
      clinical research which show a clinical picture which is strongly associated with
      patients afflicted by this syndrome. PATIENTS AND METHODS: We report a case
      series of 8 patients with CHARGE syndrome. The dental features associated with
      CHARGE syndrome are from case-reports, but without a congruity that can lead to a
      definition of the dental condition typical of the CHARGE phenotype. CONCLUSIONS:
      The systemic problems affecting these patients are predominant in compromising
      their quality of life: this is the reason for a frequent lack of a diagnostics
      and interceptive phase, relative to oral diseases. We report new oral
      pathological conditions affecting CHARGE patients. Knowledge of these
      pathological conditions may induce dentists to carry out specific diagnoses of
      these patients, thus, avoiding the deterioration of oral conditions.

PMID- 25070811
TI  - Mediastinal recurrence from ovarian cystadenocarcinoma presenting as pleuro
      pericardial cyst.
AB  - A 56 year-old woman (treated for ovarian cystadenocarcinoma 9-yrs before)
      presented a slowly increasing dyspnea. CT-scan revealed a mediastinal cyst with
      typical radiological pattern compatible with benign pleuro-pericardial cyst. The
      cyst was removed via right thoracoscopy. Surprisingly, the pathology were
      indicative of cystic mediastinal recurrence from ovarian adenocarcinoma. 

PMID- 25070809
TI  - 5-HTTLPR moderates naltrexone and psychosocial treatment responses in heavy
      drinking men who have sex with men.
AB  - BACKGROUND: A functional polymorphism (5-HTTLPR) in the promoter region of the
      serotonin transporter gene has been widely studied as a risk factor and moderator
      of treatment for a variety of psychopathologic conditions. To evaluate whether 5
      HTTLPR moderates the effects of treatment to reduce heavy drinking, we studied
      112 high-functioning European-American men who have sex with men (MSM). Subjects
      participated in a randomized clinical trial of naltrexone (NTX) and cognitive
      behavioral therapy (CBT) for problem drinking. METHODS: Subjects were treated for
      12 weeks with 100 mg/d of oral NTX or placebo (PBO). All participants received
      medical management with adjusted brief behavioral compliance enhancement
      treatment (BBCET) alone or in combination with modified behavioral self-control
      therapy (MBSCT; an amalgam of motivational interviewing and CBT). Participants
      were genotyped for the tri-allelic 5-HTTLPR polymorphism (i.e., low-activity S'
      or high-activity L' alleles). RESULTS: During treatment, the number of weekly
      heavy drinking days (HDD; defined as 5 or more standard drinks per day) was
      significantly lower in subjects with the L'L' (N = 26, p = 0.015) or L'S' (N =
      52, p = 0.016) genotype than those with the S'S' (N = 34) genotype regardless of
      treatment type. There was a significant interaction of genotype with treatment:
      For subjects with the S'S' genotype, the effects of MBSCT or NTX on HDD were
      significantly greater than the minimal intervention (i.e., BBCET or PBO, p =
      0.007 and p = 0.049, respectively). In contrast, for subjects with 1 or 2 L'
      alleles, the effects of the more intensive psychosocial treatment (MBSCT) or NTX
      did not significantly differ from BBCET or PBO. CONCLUSIONS: These preliminary
      findings support the utility of the 5-HTTLPR polymorphism for personalizing
      treatment selection in problem drinkers.

PMID- 25070812
TI  - The association between the C677T polymorphism in MTHFR gene and the risk of
      thyroid cancer: a meta-analysis.
AB  - OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important
      role in folate metabolism and MTHFR C677T polymorphism has been suggested as a
      risk factor to various cancers. It is a common genetic alteration and may affect
      the host susceptibility to thyroid cancer. The aim of this study was to
      investigate the association between MTHFR C677T polymorphism and thyroid cancer
      risk by performing a meta-analysis. MATERIALS AND METHODS: PubMed, EMbase, CNKI
      and Wanfang databases were searched for case-control studies investigating the
      association between MTHFR C677T polymorphism and thyroid cancer risk. OR with
      95%CI was used to assess this possible association. Four individual case-control
      studies with a total of 360 cases and 900 controls were included into this meta
      analysis. RESULTS: Meta-analyses showed there was significant association between
      MTHFR C677T polymorphism and thyroid cancer risk: TT vs. CC: OR = 2.06, 95% CI =
      1.04-4.10, p = 0.04; T vs. C: OR = 2.06, 95% CI = 1.97-3.77, p = 0.04.
      CONCLUSIONS: This meta-analysis supports an association between MTHFR C677T
      polymorphism and thyroid cancer risk. Further studies with large sample size and
      careful design are needed to identify this association more comprehensively.

PMID- 25070813
TI  - Genome-wide analysis of genetic variations assisted by Ingenuity Pathway Analysis
      to comprehensively investigate potential genetic targets associated with the
      progression of hepatocellular carcinoma.
AB  - OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common malignant
      tumors and the third cause of cancer death worldwide. The development of HCC is a
      multi-pathway regulated process including a variety of genetic mutations and
      variations. MATERIALS AND METHODS: To get an insight into the overall genetic
      aberration, we analyzed the gene expression profile of 9 HCC samples and 9 normal
      liver tissues as control. Genes located in these two regions of 4p16.3 and
      14q32.1 with gain or loss proceeded to in-depth analysis based on the Ingenuity
      Pathway Analysis (IPA). Through network analysis of these genes and pathways,
      molecules highly correlated with HCC and might be targeted for treatments were
      also hunted out. RESULTS: Through this method, we found two MicroRNAs (miR-943
      and miR-571) that never been reported in HCC samples before. CONCLUSIONS: Our
      study has introduced an effective method for cancer research and our work will
      greatly promote the genetic knowledge of HCC.

PMID- 25070814
TI  - Gene expression profiling of gastric cancer.
AB  - OBJECTIVES: Gastric cancer is the second leading cause of cancer-related death
      worldwide. Gene expression profile facilitates the identification of molecular
      mechanism of gastric cancer. Previous studies mainly focused on differentially
      expressed genes (DEGs) without considering MicroRNAs (miRNAs) and transcription
      factors (TFs). Here we aim to elaborate the mechanism of gastric cancer on
      transcription level with microarray data from the gene expression omnibus (GEO)
      database. MATERIALS AND METHODS: We firstly identified DEGs between gastric
      cancer and normal tissues. Then the DEGs were mapped in KEGG pathway and gene
      ontology database to conduct functional categories enrichment analysis. MiRNAs
      and TFs enriched with target DEGs were also identified. RESULTS: A total of 977
      DEGs were selected, including 492 down regulated and 485 overexpressed genes in
      gastric cancer tissue. Functional analysis revealed cell cycle, metabolism and
      ECM related biological processes as the significant items. Eight miRNAs and 20
      TFs enriched with target DEGs were detected, including one novel miRNA (miR-557)
      and four novel TFs (SPI1, NFIC, SPIB and THAP1), which have not been reported to
      be related to gastric cancer before. All of them might contribute to the
      pathogenesis since they are all related to other cancers and their target genes
      have been reported to play important roles in gastric tumorigenesis. CONCLUSIONS:
      Our results may facilitate further therapeutic studies of gastric cancer.

PMID- 25070815
TI  - Targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induces apoptosis
      of osteosarcoma cells in vitro.
AB  - OBJECTIVES: To investigate the effect of targeted antiosteosarcoma methotrexate
      bisphosphonate conjugate on growth inhibition and apoptosis in human osteosarcoma
      MG-63 cells. MATERIALS AND METHODS: MG-63 cells were treated with various
      concentrations of methotrexate-bisphosphonate conjugate and apoptosis was
      monitored via an MTT assay, cell morphology, TUNEL assay and flow cytometry
      analysis. RESULTS: The survival rate of MG-63 cells treated for 24 to 96 hours
      with 2000 mg/ml or more of methotrexate-bisphosphonate conjugate decreased
      significantly. Cells treated with conjugate showed typical apoptotic features
      using inverted phase contrast microscopy and fluorescence staining, and the
      majority of cells demonstrated a positive result in the TUNEL assay.
      Karyopyknosis and crescent aggregation of chromatin were observed in conjugate
      treated cells by electron microscopy. Flow cytometry of MG-63 cells treated with
      methotrexate-bisphosphonate conjugate showed a time and dose-dependent increase
      in apoptosis (p < 0.05). CONCLUSIONS: A targeted antiosteosarcoma methotrexate
      bisphosphonate conjugate induces apoptosis in human osteosarcoma MG-63 cells.
      This new conjugate is a valuable experimental tool for the therapy of
      osteosarcoma.

PMID- 25070816
TI  - L-arginine enhances arginine deiminase induced human lymphoma cell growth
      inhibition through NF-kBp65 and p53 expression in vitro.
AB  - OBJECTIVE: Arginine deiminase (ADI) and L-arginine (L-Arg) can act as anti-tumor
      agents in-vitro and in-vivo. However, the mechanism of ADI and L-Arg as anti
      tumor agents has not been clearly shown. MATERIALS AND METHODS: With the goal of
      understanding the role of ADI and L-Arg in inhibition of cell growth, we used the
      Ramos human lymphoma cell line, which is known to be ADI-sensitive, and observed
      the p53 and NF-kappaBp65 protein expression after ADI and arginine treatment.
      After determining an optimal experimental ADI concentration (0.01 U/ml), we
      studied the effects of ADI treatment, when combined with different concentrations
      of L-arginine (control, ADI only, ADI with 10 mM/ml Arg, ADI with 30 mM/ml Arg,
      and ADI with 50 mM/ml Arg). An MTT assay was used to assess cell survival after
      treatment, Western blot analysis to determine the levels of the NF-kappaBp65, p53
      and NO mediators and nitric oxide assays were used to determine nitrite levels.
      RESULTS AND CONCLUSIONS: L-arginine enhanced ADI-induced inhibited cell growth
      through expression of NF-kappaBp65 and p53 in a dose-dependent manner.

PMID- 25070817
TI  - The association between COX-2 expression and survival in myeloma patients.
AB  - BACKGROUND: Increased cyclooxygenase-2 (COX-2) expression has been associated
      with poor prognosis in multiple myeloma (MM). AIM: This study examined the
      relationship between COX-2 expression in bone marrow and prognosis in MM
      patients. PATIENTS AND METHODS: Bone marrow biopsy samples of 67 newly diagnosed
      MM patients were examined immunohistochemically for COX-2 expression. Mean age of
      the patients was 52.69 years (52.69 +/- 9.17) and median follow-up time was 99.5
      months (range: 6-170 months). RESULTS: Of all patients, 30 (44.8%) were COX-2
      positive and 37 (55.2%) were COX-2 negative. Median overall survival (OS) was 78
      months (range: 54.07-101.92 months) among all patients, 75 months (range: 45.61
      104.38 months) in COX-2-positive patients, and 98 months (range: 50.36-145.63
      months) in COX-2-negative patients. Median progression-free survival (PFS) was 30
      months (range: 3-134 months) in all, 29.5 months (range: 3-68 months) in COX-2
      positive and 35 months (range: 3-134 months) in COX-2-negative patients.
      Statistically significant differences in OS and PFS between COX-2-positive and
      COX-2-negative patients were not observed (p = 0.84 and p = 0.22, respectively).
      Differences between the COX-2-positive and COX-2-negative patients in gender,
      hemoglobin, beta2-microglobulin (beta2M), creatinine, albumin, and disease stage
      were not statistically significant. CONCLUSIONS: COX-2 expression neither had a
      role in prognosis nor significantly affected OS and PFS. We conclude that stem
      cell transplantation might eliminate the detrimental effects of COX-2 positivity.
      Larger series of patients are needed to investigate this observation.

PMID- 25070818
TI  - Potential role of some oxidant/antioxidant status parameters in prefrontal cortex
      of rat brain in an experimental psychosis model and the protective effects of
      melatonin.
AB  - OBJECTIVES: The etiology of schizophrenia is unknown. However, some of the
      neuropathological changes in schizophrenia may be the result of increased free
      radical-mediated or reactive oxygen species (ROS) mediated neurotoxicity.
      Melatonin is a hormone produced especially at night in the pineal gland;
      additionally is a highly important antioxidant. The aim of this study is to
      indicate the contribution effect of the neuropathophysiology of schizophrenia and
      protective effects of melatonin against this oxidative damaged. MK-801 induced
      selective neurotoxicity has been proposed as an animal model for psychosis.
      MATERIALS AND METHODS: 21 healthy adult and male Wistar albino rats were divided
      into three groups. MK-801 was given intraperitoneally for 5 days in experimental
      psychosis group. Melatonin was given to the treatment group for 6 days by
      intraperitoneally. In control group, saline was given in the same way. At the 7th
      day of the experiments, rats were killed by decapitation. Brains were removed and
      prefrontal part of the brain was divided for biochemical analyses. RESULTS: Some
      antioxidant enzymes, malondialdehyde and protein carbonyl analyses were made by
      spectrophotometric methods. SOD, GSH-Px, XO activities and malondialdehyde,
      protein carbonyl and NO levels were found to be increased significantly in
      prefrontal cortex of MK-801 group (p < 0.0001) compared to the control group. In
      melatonin treated rats, prefrontal tissue malondialdehyde and protein carbonyl
      levels were decreased significantly in comparison with MK-801 group (p < 0.0001).
      CONCLUSIONS: MK-801 may induce oxidative stress in prefrontal cortex of rats.
      This experimental study provides some evidences for the protective effects of
      melatonin on MK-801-induced changes in prefrontal rat cortex.

PMID- 25070819
TI  - Serial EEG study in a girl with Landau-Kleffner syndrome associated with
      continuous spikes and waves during slow sleep.
AB  - Landau-Kleffner syndrome (LKS) is rare epileptic encephalopathy in childhood,
      characterized by both acquired epileptic aphasia and abnormal epileptiform
      discharges in electroencephalogram (EEG). We herein report a serial EEG study in
      LKS. A 22-month old girl was referred to our hospital because of frequently
      partial seizures in her left upper limb. On EEG performed and multiforcal spikes
      were recognized. Oral treatment of carbamazepine was started but her seizures
      were not controlled. Her language ability did not progress after 2 years of her
      age. At age 4 years, carbamazepine was switched to valproic acid, leading to
      reduction in the frequency of seizure episodes. She was able to speak two-word
      sentences at 4 years of age, but her word output gradually decreased. At 5 years
      of age, addition of zonisamide further reduced the frequency of seizure episodes,
      but failed to achieve complete control of seizures. She increasingly asked for
      questions to be repeated. Auditory brainstem response testing performed at the
      department of otolaryngology revealed normal hearing ability. She was diagnosed
      as having intellectual deficits with an intelligence quotient (IQ) of 61 at 7
      years of age. The EEG at 8 years of age showed continuous spikes and waves during
      slow sleep (CSWS), leading to a diagnosis of LKS. After age 11 years, the CSWS on
      EEG improved without requiring a change in antiepileptic drugs (AEDs). Treatment
      with the oral AEDs was discontinued at 13 years of her age. Her IQ at 13 years of
      age was in the low 70s. 

PMID- 25070820
TI  - An infant with steroid-refractory cytomegalovirus-associated ADEM who responded
      to immunoglobulin therapy.
AB  - Acute disseminated encephalomyelitis (ADEM) develops via an immunological
      mechanism. We encountered a 10-month-old infant with a rare pathogenesis of
      cytomegalovirus (CMV)-related ADEM. The patients complaints were; protracted
      fever; consciousness disorder; and affected cervical stability. Cerebral magnetic
      resonance imaging (MRI) 9 days after onset, revealed a disseminated lesion,
      suggesting ADEM. Pulse therapy with methylprednisolone at 30 mg/kg was performed
      for 3 days. However, its clinical efficacy was not marked. Therapy with
      immunoglobulin (IVIg) at 400 mg/kg/day was started 15 days after onset, and
      continued for 5 days. This markedly improved the consciousness level and muscle
      strength, and the infant was discharged without neurological sequelae. ADEM
      showed a monophasic course, and the infant's subsequent growth has been
      favorable. Altough the number of case reports is small, massive-IVIg therapy
      should be considered in patients with steroid-refractory ADEM, as demonstrated in
      this case study.

PMID- 25070821
TI  - Identification crucial genes in peripheral neuropathic pain induced by spared
      nerve injury.
AB  - AIM: Peripheral neuropathic pain (PNP) is a kind of neuropathic pain caused by
      damage or disease that affects the peripheral nervous system. This study aimed to
      investigate the molecular mechanism of PNP and identify therapy targets for
      treating PNP in a spared nerve injury (SNI) model. MATERIALS AND METHODS: Gene
      expression data with accession number of GSE18803 were downloaded from Gene
      Expression Omnibus (GEO). This dataset included microarray data of four kinds of
      rat samples (adult rats with SNI, adult rats with sham injury, neonate rats with
      SNI, and neonate rats with sham injury). Differentially expressed genes (DEGs)
      were identified by using Limma software package, and further, Gene Ontology (GO)
      function and pathway analysis of DEGs were performed through the DAVID online
      tools. Protein-protein interaction (PPI) network of DEGs were constructed by
      STRING online database, and co-expression networks were constructed through
      Cytoscape. RESULTS: Totally 111 DEGs which were specially differentially
      expressed in adult rats with SNI were identified. Functional enrichment analysis
      suggest the majority of DEGs were related with immune functions. By comparing the
      three lists of genes got from GO and KEGG enrichment analysis, PPI network, and
      co-expression network analysis, 15 crucial genes were identified. CONCLUSIONS:
      Pathological nerve pain might be associated with immune dysfunctions and the 15
      crucial genes might play an important role in the development of pathological
      nerve pain and have potential to be therapy targets.

PMID- 25070822
TI  - The efficacy of radiofrequency volumetric tissue reduction of hypertrophied
      inferior turbinate in simple snoring.
AB  - BACKGROUND: Simple snoring represents a social problem, not only because it could
      affect the patient's married life, but it often goes along with sleep-disordered
      breathing. Chronic nasal obstruction has many sequel including snoring and the
      inferior turbinate hypertrophy (ITH) is its most common cause. The aim of the
      study is to evaluate the efficacy of video-assisted endoscopic radiofrequency
      volumetric tissue reduction (RFVTR) to reduce snoring in patients affected by
      chronic nasal obstruction due to ITH. PATIENTS AND METHODS: This prospective
      study was conducted over 48 habitual snoring with persistent nasal obstruction
      due to bilateral ITH refractory to medical management received one time RFVTR of
      both it. Nasal symptoms were assessed both subjectively, by Visual Analog Scale
      (VAS) and NOSE Scale, and objectively by videorhinohygrometer. Snoring was
      measured by Snoring severity rated by the bed partner, in a longitudinal fashion,
      using VAS. All patients were evaluated pre-operatively, and after 45th day (range
      35-50 days) post-operatively. RESULTS: Thirty-two subjects completed study. All
      patients had significant symptomatic improvement in nasal breathing (5.53 +/-
      2.88 vs 1.87 +/- 1.75; p < 0.05), confirmed by videorhinohygrometer values (p <
      0.05). We had a significantly improvement of snoring in all patients (5.62 +/-
      2.80 vs 1.86 +/- 1.43, p < 0.001) with a mean snoring Visual Analog Scale
      improvement of 77.4%. CONCLUSIONS: Based on this study and literature review, it
      seems that RFVTR represents a safe, minimal invasive, easy performed, and time
      and cost effective surgery, which may decrease symptoms of snoring in patients
      with ITH, at least, in short-term follow-up.

PMID- 25070823
TI  - Prognostic usefulness of IL-6 and VEGF for the occurrence of changes in coronary
      arteries of patients with stable angina and implanted stents.
AB  - AIM: The aim of this study was to determine the prognostic significance of
      interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) in patients
      with chronic coronary artery disease treated who underwent percutaneous coronary
      intervention with stent implantation, for assessing the risk of restenosis and
      the occurrence of de novo lesions. PATIENTS AND METHODS: 498 patients with stable
      angina were examined during 18 months. 50 patients with significant (> 70%)
      stenosis of one coronary artery, eligible for the implantation of one stent, were
      enrolled to the study. Il-6 and VEGF level was measured using ELISA immunoassays
      during the initial coronary angiography with simultaneous angioplasty and stent
      implantation and 4 weeks after stent implantation. Coronary angiography was
      carried out 8-12 months after stent implantation. RESULTS: Statistically
      significant increase in IL-6 (from 4.02 +/- 4.40 to 10.90 +/- 8.23) and VEGF
      (from 310.13 +/- 50.90 to 392.32 +/- 106.84) level was observed 4 weeks after
      stent implantation in the group with restenosis. CONCLUSIONS: Increased levels of
      IL-6 and VEGF in the peripheral blood of patients with chronic stable angina
      pectoris, measured 4 weeks after coronary angioplasty with stent implantation,
      may indicate an increased risk of angiographic restenosis and de novo coronary
      artery lesions.

PMID- 25070824
TI  - Clinical analysis of optimal timing for application of noninvasive positive
      pressure ventilation in treatment of AECOPD patients.
AB  - OBJECTIVES: This study is conducted to investigate an optimal timing of
      sequential noninvasive positive pressure ventilation (NPPV) applied for patients
      with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).
      PATIENTS AND METHODS: Application of NPPV for 102 patients was randomly observed
      in the conditions of a 2-hour spontaneous breathing trial (SBT-2) and pulmonary
      infection control (PIC) window. Efficiency of NPPV in treatment of the patients,
      an incidence rate of tracheal reintubation, length of time for patients received
      invasive mechanical ventilation, and a morbidity rate of ventilator-associated
      pneumonia were examined in each group of 51 patients. RESULTS: The incidence
      rates for the patients treated successfully with NPPV and for tracheal
      reintubation were shown as 88.2 and 60.8, and 11.8 and 39.2 in SBT-2 and PIC,
      respectively (both p < 0.05). Length of time (hour) for use of the invasive
      ventilation was 116 and 82.5 in SBT-2 and PIC, respectively (p < 0.05). There was
      a similar morbidity rate of ventilator-associated pneumonia seen in both groups.
      CONCLUSIONS: SBT-2 would be the optimal timing considered to use NPPV for AECOPD
      patients based on a high success rate and a low risk of tracheal reintubation.

PMID- 25070825
TI  - Anti-CD11c antibody, Efalizumab attenuate ventilator-induced lung injury.
AB  - BACKGROUND: The pathophysiology of ventilator-induced lung injury (VILI) involves
      multiple mechanisms including inflammation and inflammatory cells infiltration.
      The anti-CD11c monoclonal antibody, Efalizumab has been demonstrated to inhibit
      the T cell activation, migration and adhesion to keratinocytes. MATERIALS AND
      METHODS: In this study, we induced lung injury with mechanical ventilation in
      male Sprague-Dawley rats, the rats were divided into four groups: lung-protective
      ventilation (LV), injurious ventilation (HV), HV+human IgG control and HV+
      Efalizumab groups. Then we detected the lung tissue wet/dry ratio, and the
      activity of myeloperoxidase (MPO) was determined. The concentration of protein,
      TNF-a, IL-6, IL-1b and MIP-2 in the BALF were detected by ELISA. The expression
      ICAM-1 was measured by Realtime PCR. RESULTS: Compared with the human IgG control
      treated group, the treatment of Efalizumab attenuate the ventilator-induced lung
      injury, including the wet/dry ratio and the activity of myeloperoxidase (MPO),
      meanwhile, the level of pro-inflammatory cytokines, such as TNF-a, IL-6, IL-1b
      and MIP-2 were decreased in the BALF of Efalizumab-treated group rats compared
      with the human IgG-treated control group. In addition, the histopathological
      index of ventilator-induced lung injury was improved after efalizumab treatment,
      that also reduced the recruitment of inflammatory cells into the lung, such as
      neutrophils. CONCLUSIONS: Our data suggested that Efalizumab could protect rat
      from ventilator-induced lung injury and improve the survival time through the
      inhibition of intrapulmonary inflammatory response.

PMID- 25070826
TI  - Formononetin attenuates hydrogen peroxide (H2O2)-induced apoptosis and NF-kappaB
      activation in RGC-5 cells.
AB  - OBJECTIVES: Diabetic retinopathy is a common diabetic eye disease caused by
      changes in retinal ganglion cells (RGCs). Several studies suggest that the
      oxidative stress plays a role in the pathogenesis of diabetic retinopathy in
      adults. Formononetin is a flavone with powerful antioxidant properties that
      exists naturally in various plants and Chinese medicine. In the present study, an
      attempt has been made to investigate the antioxidative effects of formononetin on
      H2O2-induced apoptosis of RGC-5 cells. MATERIALS AND METHODS: Exposure of retinal
      ganglion cells (RGCs) to the indicated concentrations of formononetin and H2O2
      for 24 h, analyzed by MTT assay. Cells were stained with Annexin V-FITC and PI,
      analyzed by flow cytometry. And the level of superoxide anions, malondialdehyde
      (MDA, a marker of lipid peroxidation), 8-hydroxy-2-deoxyguanosine (8-OHdG,
      indicator of oxidative DNA damage) and MnSOD (manganese superoxide dismutase)
      activity were measured by kits. RESULTS: Formononetin reduced hydrogen peroxide
      (H2O2)-induced apoptosis and improved the levels or activity of indicators of
      oxidative stress. Formononetin also inhibited the activation of nuclear factor
      kappaB (NF-kappaB), which is a significant transcription factor for RGC-5
      apoptosis. CONCLUSIONS: Formononetin may be developed as a antioxidant drug to
      treat diabetic retinopathy.

PMID- 25070827
TI  - Expression of heat shock protein 90 in the kidneys of diabetic db/db mice.
AB  - OBJECTIVE: To identify novel genes regulated in diabetic nephropathy. MATERIALS
      AND METHODS: Total RNA from the renal cortex of db/+ and db/db mice was isolated
      and DNA microarrays specific for diabetes signaling pathways were used for
      expression profiling. Expression of mRNA and protein was determined by RT-PCR and
      western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated
      UTP nick-end labeling (TUNEL) assay and immunohistochemical staining were
      assessed in renal cortex of db/db mice. RESULTS: Microarray data revealed that 7
      genes show up- or down-regulated pattern and diabetic mice specifically decreased
      heat shock protein (Hsp) 90alpha expression of genes compared to control mice
      (diabetic mice 0.68 vs. control mice 1 relative density). Expression of
      Hsp90alpha mRNA and Hsp90 protein was significantly decreased in the renal cortex
      of diabetic mice. However, Hsp70 mRNA and protein expression was not changed.
      Apoptosis was increased in glomeruli of diabetic mice due to increased expression
      of cleaved caspase-3 and Bax. CONCLUSIONS: Our results suggest that Hsp 90
      expression was decreased in diabetic glomeruli and decreased Hsp90 expression may
      mediate podocyte apoptosis in type 2 diabetic kidneys.

PMID- 25070828
TI  - Cardiovascular disease in diabetes.
AB  - OBJECTIVES: Obesity and type 2 diabetes (T2D) are major risk factors for
      cardiovascular disease (CVD), which is often fatal among diabetics. There has
      been a steady rise in obesity and in associated CVD in the last 2 decades.
      Despite improvements in clinical and treatment approaches, the prevalence of
      heart failure (HF) is rising with only minor extension in survival. Obesity and
      diabetes can potentially increase the risk of HF independent of coronary heart
      disease and hypertension. Aim of this paper was to systematically review
      literature in the last 10 years on the association of CVD with obesity and
      diabetes and to address the key clinical points relevant for diagnosis and risk
      factor assessment. METHODS: Original research articles addressing molecular
      mechanisms, clinical articles and reviews published in the last 10 years in the
      area of diabetes and heart disease have been collected from different sources
      including PubMed, Scopus and other databases and critically compiled. RESULTS:
      Insulin resistance, common to both T1D and T2D patients, is a major risk factor
      for cardiovascular events. Association of hyperglycemia with insulin resistance
      further increases the risk of CVD and heart failure. Even though obesity is an
      important risk factor for CVD, the risk is mediated mostly through insulin
      resistance but not body-mass index. The total risk of CVD in T2D patients cannot
      be explained by traditional risk factors alone and specific metabolic changes
      also significantly contribute to this. CONCLUSIONS: The risk from the traditional
      cardiovascular risk factors for developing heart disease is further aggravated in
      diabetes. The treatment approach for diabetic patients to prevent cardiovascular
      complications should aim not only to control insulin resistance but should
      include lifestyle changes and early pharmacological intervention.

PMID- 25070829
TI  - Metabolic signaling of insulin secretion by pancreatic beta-cell and its
      derangement in type 2 diabetes.
AB  - Pancreatic beta-cell is responsible for insulin secretion in response to the
      availability of nutrients. Type 2 diabetes mellitus (T2D) is the result of
      pancreatic b-cell failure to supply sufficient amount of insulin accompanied with
      decreased sensitivity of the body tissues to respond to insulin. The insulin
      secretion apparatus of beta-cell is uniquely equipped with multiple metabolic and
      signaling steps that are under rigorous control. The metabolic machinery of beta
      cell is designed to sense the fluctuations in blood glucose level and supply
      insulin accordingly to the needs of body. Besides glucose, amino acids including
      glutamine and leucine and also fatty acids are known to either stimulate the beta
      cell directly or potentiate the glucose stimulated insulin secretion (GSIS)
      response. Glucose metabolism dependent GSIS is linked with the production of ATP
      that is needed for K+ATP channel inhibition and influx of calcium, necessary for
      insulin granule exocytosis. Besides glucose metabolism, amino acid metabolism and
      lipid metabolism derived metabolites mediate the optimal glucose response of beta
      cells to secrete insulin. Metabolites derived from nutrient secretagogues that
      directly or indirectly participate in the enhancement of GSIS are considered as
      metabolic coupling factors. In this review, we will discuss the regulation of
      insulin secretion by b-cell keeping the recent developments in metabolic
      signaling in focus. The relevant metabolic pathways in pancreatic beta-cell and
      their role in the control of fuel-stimulated insulin secretion will be reviewed
      to arrive at a consensus picture with respect to the metabolic signaling of
      insulin secretion.

PMID- 25070830
TI  - The anti-inflammatory effects of 1,1 dimethyl-4-phenylpiperazinium (DMPP)
      compared to dexamethasone in a guinea pig model of ovalbumin induced asthma.
AB  - BACKGROUND AND AIM: Inflammatory cells involved in the pathophysiology of asthma
      express nicotinic receptor. Therefore 1,1 dimethyl(-4-)phenylpiperazinium (DMPP)
      in two doses were compared to dexamethasone in asthmatic guinea pigs. MATERIALS
      AND METHODS: Six groups were included; Normal control and five asthmatic (OVA
      sensitized and challenged) groups; which were treated for 10 days as follows: two
      vehicles, dexamethasone (DEXA, 1 mg/kg) and DMPP (0.4 and 0.8 mg/kg) groups.
      Pulmonary functions and airway hyper-responsiveness were assessed. Leukocytic
      count, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) and
      immunoglobulin E (IgE) were measured in both blood and bronchoalveolar lavage
      fluid (BALF). Histopathological examination of the lung tissues was conducted.
      RESULTS: Asthmatic untreated animals exhibited significant increase in early and
      late airway resistance (RxV) and airway hyper-responsiveness, with reduction in
      tidal volume. Both blood and BALF showed significant increase in total leukocytic
      count (TLC), eosinophils, lymphocytes, monocytes, TNF-alpha, IL-6 and IgE with
      significant decrease in neutrophils. Airway inflammatory cell infiltration and
      smooth muscle thickness significantly increased. DMPP 0.4 mg/kg significantly
      decreased late phase RXV, TLC, BALF lymphocytes, TNF-alpha, smooth muscle
      thickness and increased neutrophils in BALF over both DEXA and DMPP 0.8 mg/kg.
      Moreover, DMPP 0.4 mg/kg significantly decreased IL-6 and BALF eosinophils than
      DMPP 0.8 mg/kg and decreased serum IgE and parenchymal inflammatory infiltration
      than DEXA. CONCLUSIONS: Low dose DMPP has more anti-inflammatory effect than a
      high dose in most parameters and sometimes than dexamethasone. Cholinergic anti
      inflammatory pathway may therefore represent a potential drug target for allergic
      asthma. The dose related effect of DMPP and the mechanism underlying this effect
      require further evaluation.

PMID- 25070831
TI  - The impact of pharmacovigilance on drug portfolio management.
AB  - This review examines the influence of pharmacovigilance on drug portfolio. As a
      result of pharmacovigilance studies, actions are taken by national drug
      administrations and/or the World Health Organization (WHO) that have a strong
      impact on drug portfolio management: drug withdrawal from medical practice,
      discovery of new therapeutic indications, discovery of drug interactions,
      preference for specific pharmaceutical formulations, discovery of
      contraindications and change of drug prescription status. 

PMID- 25070832
TI  - Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor
      pathway in nasal cells.
AB  - Leptin is involved in the lung epithelial homeostasis. Its role in the nasal
      tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen
      exposure leading to consequential structural abnormalities in the nasal
      epithelium. Topical corticosteroids are recommended as first-line therapy in AR.
      Parietaria pollen is one of the most important allergenic sources in the southern
      Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to
      determine whether allergen stimulation acts on leptin/leptin receptor pathway and
      how fluticasone furoate (FF) influences this pathway. The effects of the major
      allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-beta1 on
      cell proliferation, on leptin/leptin receptor expression and modulation (by
      clonogenic test, by RT-q-RT-PCR, by immunocytochemistry and by flow-cytometry),
      and on STAT-3 activation (assessing nuclear translocation by western blot
      analysis) were assessed. We found that rPar j 1 and TGF-beta1 significantly
      decreased cell proliferation and down-regulated the leptin/leptin receptor
      pathway, whereas FF and leptin reverted them, both alone and in combination.
      Furthermore, rPar j 1 reduced, while leptin and FF increased STAT-3 activation.
      In conclusion, FF and leptin itself are able to preserve nasal epithelial
      homeostasis restoring the leptin/leptin receptor pathway altered by rPar j 1
      exposure.

PMID- 25070833
TI  - Trigonelline and diosgenin attenuate ER stress, oxidative stress-mediated damage
      in pancreas and enhance adipose tissue PPARgamma activity in type 2 diabetic
      rats.
AB  - Type 2 Diabetes mellitus (T2DM) is characterized by peripheral insulin
      resistance, impaired insulin secretion, and reduced beta-cell mass. Mechanisms
      that underlie beta-cell failure include glucotoxicity, lipotoxicity, endoplasmic
      reticulum (ER) stress, and oxidative stress. This study was designed to assess
      the protective effect of trigonelline and diosgenin against changes in ER stress
      associated apoptotic proteins CHOP, Caspase12, and Caspase3 and antioxidant
      levels in pancreas as well as adipose tissue PPARgamma mRNA in T2DM rats. Markers
      of diabetes and obesity such as serum glucose, insulin, free fatty acid (FFA),
      TNF-alpha, IL-6, and leptin were also assessed. T2DM rats showed significantly
      elevated levels of pancreatic ER stress proteins and lipid peroxidation, while
      the antioxidants were significantly reduced. Histological examination also
      confirmed T2DM-associated damage in pancreas. In addition, a significant increase
      in serum FFA, TNF-alpha, IL-6, and decrease in leptin levels along with
      significantly decreased adipose mass and reduced PPARgamma expression were
      observed in T2DM rats. On the other hand, trigonelline and diosgenin treatment
      independently brought about significant improvement in serum parameters, decrease
      in apoptotic ER stress proteins, and reinforced antioxidant status in pancreas.
      Histological examination of pancreas showed normal morphology. Treated groups
      also showed increased adipose tissue mass and enhanced PPARgamma expression. Data
      from docking studies indicated good interaction of both compounds with PPARgamma,
      and diosgenin showed better binding efficiency. These findings suggest that the
      insulin-sensitizing effects of trigonelline and diosgenin are mediated through
      moderation of ER stress and oxidative stress in pancreas as well as by PPARgamma
      activation in adipose tissue.

PMID- 25070834
TI  - SRJ23, a new semisynthetic andrographolide derivative: in vitro growth inhibition
      and mechanisms of cell cycle arrest and apoptosis in prostate cancer cells.
AB  - PURPOSE: 3,19-(3-Chloro-4-fluorobenzylidene)andrographolide (SRJ23), a new
      semisynthetic derivative of andrographolide (AGP), exhibited selectivity against
      prostate cancer cells in the US National Cancer Institute (NCI) in vitro anti
      cancer screen. Herein, we report the in vitro growth inhibition and mechanisms of
      cell cycle arrest and apoptosis induced by SRJ23. METHODS: 3-(4,5-Dimethythiazol
      2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used in assessing in vitro
      growth inhibition of compounds against prostate cancer (PC-3, DU-145 and LNCaP)
      and mouse macrophage (RAW 264.7) cell lines. Flow cytometry was utilised to
      analyse cell cycle distribution, whereas fluorescence microscopy was performed to
      determine morphological cell death. DNA fragmentation and annexin V-fluorescein
      isothiocyanate (FITC)/propidium iodide (PI) flow cytometry were done to confirm
      apoptosis induced by SRJ23. Quantitation of cell cycle and apoptotic regulatory
      proteins were determined by immunoblotting. RESULTS: AGP and SRJ23 selectively
      inhibited the growth of prostate cancer cells compared with RAW 264.7 cells at
      low micromolar concentrations; however, SRJ23 was more potent. Mechanistically,
      SRJ23-treated PC-3 cells displayed down-regulation of cyclin-dependent kinase
      (CDK) 1 without affecting levels of CDK4 and cyclin D1. However, SRJ23 induced
      down-regulation of CDK4 and cyclin D1 but without affecting CDK1 in DU145 and
      LNCaP cell lines. DNA histogram analysis revealed that the SRJ23 induced G2/M in
      PC-3 cells but G1 arrest in DU-145 and LNCaP cells. Morphologically, both
      compounds induced predominantly apoptosis, which was further confirmed by DNA
      fragmentation and annexin V-FITC staining. The DNA fragmentation was inhibited in
      the presence of caspase 8 inhibitor (Z-IETD-FMK). Apoptosis was associated with
      an increase in caspase 8 expression and activation. This thought to have induced
      cleavage of Bid into t-Bid. Additionally, increased expression and activation of
      caspase 9 and Bax proteins were apparent, with a concomitant down-regulation of
      Bcl-2 protein. Similar apoptosis cascade of events was observed in SRJ23-treated
      DU145 and LNCaP cell lines. CONCLUSION: SRJ23 inhibited the growth of prostate
      cancer cells by inducing G2/M and G1 arrest via down-regulation of CDK1, and CDK4
      and cyclin, respectively, and initiated caspase-8-mediated mitochondrial
      apoptosis. Taken together, these data support the potential of this compound as a
      new anti-prostate cancer agent.

PMID- 25070835
TI  - Context and group dynamics in a CBPR-developed HIV prevention intervention.
AB  - This paper will explore in detail the effects of context and group dynamics on
      the development of a multi-level community-based HIV prevention intervention for
      crack cocaine users in the San Salvador Metropolitan Area, El Salvador. Community
      partners included residents from marginal communities, service providers from the
      historic center of San Salvador and research staff from a non-profit
      organization. The community contexts from which partners came varied considerably
      and affected structural group dynamics, i.e. who was identified as community
      partners, their research and organizational capacity, and their ability to
      represent their communities, with participants from marginal communities most
      likely to hold community leadership positions and be residents, and those from
      the center of San Salvador most likely to work in religious organizations
      dedicated to HIV prevention or feeding indigent drug users. These differences
      also affected the intervention priorities of different partners. The context of
      communities changed over time, particularly levels of violence, and affected
      group dynamics and the intervention developed. Finally, strategies were needed to
      elicit input from stakeholders under-represented in the community advisory board,
      in particular active crack users, in order to check the feasibility of the
      proposed intervention and revise it as necessary. Because El Salvador is a very
      different context than that in which most CBPR studies have been conducted, our
      results reveal important contextual factors and their effects on partnerships not
      often considered in the literature. 

PMID- 25070837
TI  - Antibodies to DNA repair proteins in headache with neurological deficits and
      cerebrospinal fluid lymphocytosis (HaNDL) patients.
AB  - Autoimmune mechanisms have been implicated in the pathogenesis of headache and
      neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL). Pooled sera
      of five HaNDL patients and 30 controls (10 multiple sclerosis patients, 10
      migraine patients, 10 healthy controls) were screened by protein macroarray. All
      sera were also individually subjected to immunoprecipitation with neuroblastoma
      cells and the bound antigens were identified by mass spectrometry. Antibodies to
      three DNA repair proteins (mitogen-activated protein kinase-4, DNA-dependent
      protein kinase catalytic subunit, DNA excision repair protein ERCC-6) were
      identified by both macroarray and immunoprecipitation methods in 3/5 HaNDL sera,
      but in none of the controls. The presence of DNA repair protein antibodies
      indicates DNA damage and provides further support for the inflammatory etiology
      of HaNDL.

PMID- 25070836
TI  - PI3K/mTOR inhibition markedly potentiates HDAC inhibitor activity in NHL cells
      through BIM- and MCL-1-dependent mechanisms in vitro and in vivo.
AB  - PURPOSE: The aim of this study is to explore the efficacy and define mechanisms
      of action of coadministration of the PI3K/mTOR inhibitor BEZ235 and pan-HDAC
      inhibitor panobinostat in diffuse large B-cell lymphoma (DLBCL) cells.
      EXPERIMENTAL DESIGN: Various DLBCL cells were exposed to panobinostat and BEZ235
      alone or together after which apoptosis and signaling/survival pathway
      perturbations were monitored by flow cytometry and Western blot analysis. Genetic
      strategies defined the functional significance of such changes, and xenograft
      mouse models were used to assess tumor growth and animal survival. RESULTS:
      Panobinostat and BEZ235 interacted synergistically in ABC-, GC-, and double-hit
      DLBCL cells and MCL cells but not in normal CD34(+) cells. Synergism was
      associated with pronounced AKT dephosphorylation, GSK3
      dephosphorylation/activation, Mcl-1 downregulation, Bim upregulation, increased
      Bcl-2/Bcl-xL binding, diminished Bax/Bak binding to Bcl-2/Bcl-xL/Mcl-1, increased
      gammaH2A.X phosphorylation and histone H3/H4 acetylation, and abrogation of
      p21(CIP1) induction. BEZ235/panobinostat lethality was not susceptible to
      stromal/microenvironmental forms of resistance. Genetic strategies confirmed
      significant functional roles for AKT inactivation, Mcl-1 downregulation, Bim
      upregulation, and Bax/Bak in synergism. Finally, coadministration of BEZ235 with
      panobinostat in immunocompromised mice bearing SU-DHL4-derived tumors
      significantly reduced tumor growth in association with similar signaling changes
      observed in vitro, and combined treatment increased animal survival compared with
      single agents. CONCLUSIONS: BEZ235/panobinostat exhibits potent anti-DLBCL
      activity, including in poor-prognosis ABC- and double-hit subtypes, but not in
      normal CD34(+) cells. Synergism is most likely multifactorial, involving AKT
      inactivation/GSK3 activation, Bim upregulation, Mcl-1 downregulation, enhanced
      DNA damage, and is operative in vivo. Combined PI3K/mTOR and HDAC inhibition
      warrants further attention in DLBCL.

PMID- 25070838
TI  - The debate on the link between subclinical hypothyroidism and childhood migraine:
      is initial endocrinological evaluation necessary for children with migraine?
AB  - Subclinical hypothyroidism (SH) is characterized by mildly elevated thyroid
      stimulating hormone (TSH) levels with normal serum-free thyroxine (fT4). While
      the prevalence of SH is 2 % in pediatric population, it has been reported much
      higher in children with migraine headache. In this study, the presence of
      subclinical hypothyroidism and associated endocrinological abnormalities in
      children with migraine naive to treatment was investigated. Children with
      migraine who were diagnosed in Pediatric Neurology Clinic based on the second
      edition of the International Classification of Headache Disorders and who did not
      receive any medication were recruited in this cross-sectional study. All patients
      were examined by the same pediatric endocrinologist and anthropometric
      measurements, systemic blood pressure, pubertal stages were recorded. Fasting
      serum levels of thyroid function tests, lipids, glucose and insulin were
      obtained. Ninety-eight children (55 female) with a mean age of 11.45 +/- 3.1
      years were evaluated. Of those, 39 were prepubertal and 59 were pubertal.
      Subclinical hypothyroidism (TSH >= 5.0 mIU/L with normal fT4) was detected in
      five patients (5.1 %); none had positive thyroid antibodies. Other conditions
      were obesity (n = 6), hirsutism (n = 4), short stature (n = 3), polycystic
      ovaries (PCO, n = 3), precocious puberty (n = 2) and gynecomastia (n = 1). Of
      five patients with SH, only one had obesity. Our results revealed that the
      prevalence of SH in children with migraine is not as high as previously reported.
      Since no significant endocrinologic disturbance was found in those children, we
      suggest that the initial endocrinological evaluation or screening for SH is
      unnecessary.

PMID- 25070840
TI  - Ultra-trace level determination of diquat and paraquat residues in surface and
      drinking water using ion-pair liquid chromatography with tandem mass
      spectrometry: a comparison of direct injection and solid-phase extraction
      methods.
AB  - Direct injection and solid-phase extraction methods for the determination of
      diquat and paraquat in surface and drinking water were developed using liquid
      chromatography with tandem mass spectrometry. The signal intensities of analytes
      based on six ion-pairing reagents were compared with each other, and 12.5 mM
      nonafluoropentanoic acid was selected as the best suited amongst them. A clean-up
      method was developed using Oasis hydrophilic-lipophilic balance; this was
      compared to the direct injection method, with respect to limits of detection,
      interference, precision, and accuracy. Limits of quantification of diquat and
      paraquat were 0.03 and 0.01 MUg/L using the direct injection method, and 0.002
      and 0.001 MUg/L using the hydrophilic-lipophilic balance method. When the
      hydrophilic-lipophilic balance method was used to analyze target compounds in 114
      surface water and 30 drinking water samples, paraquat and diquat were detected
      within a concentration range of 0.001-0.12 and 0.002-0.038 MUg/L in surface
      water, respectively. When the direct injection method was used to analyze target
      compounds in the same samples, the detected concentrations of paraquat and diquat
      were within 25% in samples being >0.015 MUg/L using the hydrophilic-lipophilic
      balance method. The liquid chromatography with tandem mass spectrometry method
      using direct injection can thus be used for routine monitoring of paraquat and
      diquat in surface and drinking water. 

PMID- 25070839
TI  - Ferritins as nanoplatforms for imaging and drug delivery.
AB  - INTRODUCTION: Due to unique architecture and surface properties, ferritin has
      emerged as an important class of biomaterial. Many studies suggest that ferritin
      and its derivatives hold great potential in a wide range of bio-applications.
      AREAS COVERED: In this review, we summarize recent progress on employing
      ferritins as a platform to construct functional nanoparticles for applications in
      MRI, optical imaging, cell tracking, and drug delivery. EXPERT OPINION: As a
      natural polymer, ferritins afford advantages such as high biocompatibility, good
      biodegradability, and a relatively long plasma half-life. These attributes put
      ferritins ahead of conventional materials in clinical translation for imaging and
      drug delivery purposes.

PMID- 25070841
TI  - JNK2 regulates the functional plasticity of naturally occurring T regulatory
      cells and the enhancement of lung allergic responses.
AB  - Glucocorticoid-induced TNFR family-related protein (GITR)-mediated activation of
      JNK was shown to regulate the suppressive activity of CD4(+)CD25(+) naturally
      occurring T regulatory cells (nTregs) in wild-type (WT) hosts. In this study,
      CD4(+)CD25(+) T cells were shown to be capable of becoming pathogenic effector
      cells in sensitized and challenged CD8(-/-) recipient mice. Only GITR-expressing
      CD4(+)CD25(+) T cells, but neither GITR knocked-in CD4(+)CD25(-) T cells nor GITR
      silenced CD4(+)CD25(+) T cells, enhanced development of lung allergic responses.
      Inhibition of JNK in WT nTregs or nTregs from GITR(-/-)and JNK2(-/-) mice failed
      to enhance lung allergic responses in sensitized and challenged CD8(-/-)
      recipient mice. The failure to enhance responses was associated with increased
      bronchoalveolar lavage fluid levels of IL-10 and TGF-beta and decreased levels of
      IL-5, IL-6, and IL-13. In contrast, nTregs from JNK1(-/-) mice, similar to WT
      nTregs, were fully effective in enhancing responses. Thus, GITR stimulation of
      nTregs and signaling through JNK2, but not JNK1, triggered the loss of regulatory
      function while concomitantly gaining pathogenic CD4(+) T effector cell function
      responsible for exacerbating asthma-like immunopathology. 

PMID- 25070843
TI  - Transcription factor ABF-1 suppresses plasma cell differentiation but facilitates
      memory B cell formation.
AB  - Ag-primed B cells that result from an immune response can form either memory B
      cells or Ab-secreting plasma cells; however, the molecular machinery that
      controls this cellular fate is poorly understood. In this study, we show that
      activated B cell factor-1 (ABF-1), which encodes a basic helix-loop-helix
      transcriptional repressor, participates in this regulation. ABF-1 was prevalently
      expressed in purified memory B cells and induced by T follicular helper cell
      mediated signals. ABF-1 expression declined by the direct repression of B
      lymphocyte-induced maturation protein-1 during differentiation. Ectopic
      expression of ABF-1 reduced the formation of Ab-secreting cells in an in vitro
      differentiation system of human memory B cells. Accordingly, knockdown of ABF-1
      potentiates the formation of Ab-secreting cells. A transgenic mouse that
      expresses inducible ABF-1 in a B cell-specific manner was generated to
      demonstrate that the formation of germinal center and memory B cells was
      augmented by induced ABF-1 in an immune response, whereas the Ag-specific plasma
      cell response was dampened. This effect was associated with the ability of ABF-1
      to limit cell proliferation. Together, our results demonstrate that ABF-1
      facilitates formation of memory B cells but prevents plasma cell differentiation.

PMID- 25070844
TI  - Macrophage depletion abates Porphyromonas gingivalis-induced alveolar bone
      resorption in mice.
AB  - The role of the macrophage in the immunopathology of periodontitis has not been
      well defined. In this study, we show that intraoral inoculation of mice with
      Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a
      significant increase in F4/80(+) macrophages in gingival and submandibular lymph
      node tissues. Macrophage depletion using clodronate-liposomes resulted in a
      significant reduction in F4/80(+) macrophage infiltration of gingival and
      submandibular lymph node tissues and significantly (p < 0.01) less P. gingivalis
      induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In
      both mouse strains, the P. gingivalis-specific IgG Ab subclass and serum cytokine
      [IL-4, IL-10, IFN-gamma, and IL-12 (p70)] responses were significantly (p < 0.01)
      lower in the macrophage-depleted groups. Macrophage depletion resulted in a
      significant reduction in the level of P. gingivalis infection, and the level of
      P. gingivalis infection was significantly correlated with the level of alveolar
      bone resorption. M1 macrophages (CD86(+)), rather than M2 macrophages (CD206(+)),
      were the dominant macrophage phenotype of the gingival infiltrate in response to
      P. gingivalis infection. P. gingivalis induced a significant (p < 0.01) increase
      in NO production and a small increase in urea concentration, as well as a
      significant increase in the secretion of IL-1beta, IL-6, IL-10, IL-12 (p70),
      eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage
      inflammatory protein-alpha and -beta, and TNF-alpha in isolated murine
      macrophages. In conclusion, P. gingivalis infection induced infiltration of
      functional/inflammatory M1 macrophages into gingival tissue and alveolar bone
      resorption. Macrophage depletion reduced P. gingivalis infection and alveolar
      bone resorption by modulating the host immune response. 

PMID- 25070842
TI  - A novel murine cytomegalovirus vaccine vector protects against Mycobacterium
      tuberculosis.
AB  - Tuberculosis remains a global health problem so that a more effective vaccine
      than bacillus Calmette-Guerin is urgently needed. Cytomegaloviruses persist
      lifelong in vivo and induce powerful immune and increasing ("inflationary")
      responses, making them attractive vaccine vectors. We have used an m1-m16-deleted
      recombinant murine CMV (MCMV) expressing Mycobacterium tuberculosis Ag 85A to
      show that infection of mice with this recombinant significantly reduces the
      mycobacterial load after challenge with M. tuberculosis, whereas control empty
      virus has a lesser effect. Both viruses induce immune responses to H-2(d)
      restricted epitopes of MCMV pp89 and M18 Ags characteristic of infection with
      other MCMVs. A low frequency of 85A-specific memory cells could be revealed by in
      vivo or in vitro boosting or after challenge with M. tuberculosis. Kinetic
      analysis of M. tuberculosis growth in the lungs of CMV-infected mice shows early
      inhibition of M. tuberculosis growth abolished by treatment with NK-depleting
      anti-asialo ganglio-N-tetraosylceramide Ab. Microarray analysis of the lungs of
      naive and CMV-infected mice shows increased IL-21 mRNA in infected mice, whereas
      in vitro NK assays indicate increased levels of NK activity. These data indicate
      that activation of NK cells by MCMV provides early nonspecific protection against
      M. tuberculosis, potentiated by a weak 85A-specific T cell response, and they
      reinforce the view that the innate immune system plays an important role in both
      natural and vaccine-induced protection against M. tuberculosis. 

PMID- 25070846
TI  - Ubiquitin-specific protease 2b negatively regulates IFN-beta production and
      antiviral activity by targeting TANK-binding kinase 1.
AB  - TANK-binding kinase 1 (TBK1) is essential for IFN regulatory factor 3 activation
      and IFN-beta production downstream of various innate receptors. However, how TBK1
      activation is terminated is not well defined. In this study, we identified
      ubiquitin-specific protease (USP) 2b as a new negative regulator for TBK1
      activation. Overexpression of USP2b inhibited retinoic acid-inducible gene-I
      mediated IFN-beta signaling; in contrast, knockdown of USP2b expression by small
      interfering RNA enhanced retinoic acid-inducible gene-I-mediated IFN-beta
      signaling. Coimmunoprecipitation experiments demonstrated that USP2b interacted
      with TBK1. As a deubiquitinating enzyme, USP2b was demonstrated to cleave K63
      linked polyubiquitin chains from TBK1 to inhibit TBK1 kinase activity. Consistent
      with the inhibitory roles of USP2b on TBK1 activation, knockdown of USP2b
      significantly inhibited the replication of vesicular stomatitis virus, whereas
      overexpression of USP2b resulted in enhanced replication of vesicular stomatitis
      virus. Therefore, our findings demonstrated that USP2b deubiquitinates K63-linked
      polyubiquitin chains from TBK1 to terminate TBK1 activation and negatively
      regulate IFN-beta signaling and antiviral immune response. 

PMID- 25070845
TI  - CaMKIV-dependent preservation of mTOR expression is required for autophagy during
      lipopolysaccharide-induced inflammation and acute kidney injury.
AB  - Autophagy, an evolutionarily conserved homeostasis process regulating biomass
      quantity and quality, plays a critical role in the host response to sepsis.
      Recent studies show its calcium dependence, but the calcium-sensitive regulatory
      cascades have not been defined. In this study, we describe a novel mechanism in
      which calcium/calmodulin-dependent protein kinase IV (CaMKIV), through inhibitory
      serine phosphorylation of GSK-3beta and inhibition of FBXW7 recruitment, prevents
      ubiquitin proteosomal degradation of mammalian target of rapamycin (mTOR) and
      thereby augments autophagy in both the macrophage and the kidney. Under the
      conditions of sepsis studied, mTOR expression and activity were requisite for
      autophagy, a paradigm countering the current perspective that prototypically,
      mTOR inhibition induces autophagy. CaMKIV-mTOR-dependent autophagy was
      fundamentally important for IL-6 production in vitro and in vivo. Similar
      mechanisms were operant in the kidney during endotoxemia and served a
      cytoprotective role in mitigating acute kidney injury. Thus, CaMKIV-mTOR
      dependent autophagy is conserved in both immune and nonimmune/parenchymal cells
      and is fundamental for the respective functional and adaptive responses to septic
      insult. 

PMID- 25070847
TI  - Intrahepatic activation of naive CD4+ T cells by liver-resident phagocytic cells.
AB  - Naive T cell activation is normally restricted to the lymphoid organs, in part
      because of their limited ability to migrate into the parenchyma of peripheral
      tissues. The liver vasculature is unique, however, and circulating leukocytes
      within the hepatic sinusoids have direct access to liver-resident cells, which
      include an abundant population of Kupffer cells. It is well accepted that
      recognition of cognate Ag within the liver leads to naive CD8(+) T cell
      activation in situ, but it is unclear whether the liver also supports naive
      CD4(+) T cell activation. In this study, we show that naive CD4(+) T cells can be
      activated to proliferate in the liver when cognate Ag expression is induced in
      hepatocytes by recombinant adeno-associated viral vectors. Ag-specific retention
      and activation of naive CD4(+) T cells within the liver are independent of
      lymphoid tissues but dependent on a clodronate liposome-sensitive population of
      liver-resident phagocytic cells. To our knowledge, this study provides the first
      unequivocal evidence that naive CD4(+) T cells can be activated in a nonlymphoid
      organ. It also gives critical insight into how CD4(+) T cells specific for Ag
      expressed in the liver are recruited to participate in protective or pathological
      responses during hepatotropic infections and autoimmune liver disease. 

PMID- 25070849
TI  - Independent of plasmacytoid dendritic cell (pDC) infection, pDC triggered by
      virus-infected cells mount enhanced type I IFN responses of different composition
      as opposed to pDC stimulated with free virus.
AB  - Upon treatment with vesicular stomatitis virus (VSV) particles, plasmacytoid
      dendritic cells (pDC) are triggered to mount substantial type I IFN responses,
      whereas myeloid DC (mDC) are only minor producers. Interestingly, bone marrow
      derived (BM-)mDC were more vulnerable to infection with enhanced GFP (eGFP)
      expressing VSV (VSVeGFP) than BM-pDC. BM-pDC stimulated with wild-type VSV
      mounted TLR-dependent IFN responses that were independent of RIG-I-like helicase
      (RLH) signaling. In contrast, in BM-pDC the VSV variant M2 induced particularly
      high IFN responses triggered in a TLR- and RLH-dependent manner, whereas BM-mDC
      stimulation was solely RLH-dependent. Importantly, VSVeGFP treatment of BM-pDC
      derived from IFN-beta yellow fluorescent protein (YFP) reporter mice (messenger
      of IFN-beta) resulted in YFP(+) and eGFP(+) single-positive cells, whereas among
      messenger of IFN-beta-BM-mDC most YFP(+) cells were also eGFP(+). This
      observation indicated that unlike mDC, direct virus infection was not required to
      trigger IFN responses of pDC. VSV-infected BM-mDC triggered BM-pDC to mount
      significantly higher IFN responses than free virus particles. Stimulation with
      infected cells enhanced the percentages of pDC subsets expressing either IFN
      beta(+) or IFN-alpha6(+) plus IFN-beta(+). Irrespective of whether stimulated
      with free virus or infected cells, IFN induction was dependent on autophagy of
      pDC, whereas autophagy of the infected mDC was dispensable. Collectively, these
      results indicated that productive VSV infection was needed to trigger IFN
      responses of mDC, but not of pDC, and that IFN responses were primarily induced
      by virus-infected cells that stimulated pDC in a TLR-dependent manner. 

PMID- 25070848
TI  - TLR4 activation enhances the PD-L1-mediated tolerogenic capacity of colonic CD90+
      stromal cells.
AB  - Signaling via programmed death ligand-1 (PD-L1) and PD-L2 is crucial for
      maintaining peripheral tolerance. CD90(+) myofibroblasts/fibroblasts (CMFs) are
      major programmed cell death-1 (PD-1) ligand-expressing cells in normal human
      colonic mucosa. CMFs suppress activated CD4(+) T cell proliferation via PD-1
      ligands. It is not known whether signaling through TLRs contribute to the
      regulation PD-1 ligands on CMFs upon colonic mucosal tolerance. In this study, we
      demonstrated that stimulation of TLR4 on human CMFs upregulates PD-L1, but not PD
      L2, and reinforces CMF-mediated suppression of CD4(+) T cell proliferation and
      IFN-gamma production. TLR4-mediated upregulation of PD-L1 on CMFs involved NF
      kappaB pathways and was JAK2 and MyD88 dependent. MyD88-dependent stimulation of
      TLR1/2 and TLR5 also upregulated PD-L1 expression on CMFs in culture. PD-L1
      expression was drastically decreased in vivo in the colonic mucosa of mice devoid
      of MyD88. Induction of MyD88 deficiency in CMFs in fibroblast-specific MyD88
      conditional knockout mice resulted in a strong increase in a mucosal IFN-gamma
      expression concomitantly with the abrogation of PD-L1 expression in CMFs under
      homeostasis and epithelial injury induced by dextran sodium sulfate. Together,
      these data suggest that MyD88-dependent TLR stimulation of CMFs in the normal
      colonic mucosa may reinforce these cells' anti-inflammatory capacity and thus
      contribute to the maintenance of mucosal tolerance. 

PMID- 25070850
TI  - Inhibition of two temporal phases of HIV-1 transfer from primary Langerhans cells
      to T cells: the role of langerin.
AB  - Epidermal Langerhans cells (eLCs) uniquely express the C-type lectin receptor
      langerin in addition to the HIV entry receptors CD4 and CCR5. They are among the
      first target cells to encounter HIV in the anogenital stratified squamous mucosa
      during sexual transmission. Previous reports on the mechanism of HIV transfer to
      T cells and the role of langerin have been contradictory. In this study, we
      examined HIV replication and langerin-mediated viral transfer by authentic
      immature eLCs and model Mutz-3 LCs. eLCs were productively infected with HIV,
      whereas Mutz-3 LCs were not susceptible because of a lack of CCR5 expression. Two
      successive phases of HIV viral transfer to T cells via cave/vesicular trafficking
      and de novo replication were observed with eLCs as previously described in
      monocyte-derived or blood dendritic cells, but only first phase transfer was
      observed with Mutz-3 LCs. Langerin was expressed as trimers after cross-linking
      on the cell surface of Mutz-3 LCs and in this form preferentially bound HIV
      envelope protein gp140 and whole HIV particles via the carbohydrate recognition
      domain (CRD). Both phases of HIV transfer from eLCs to T cells were inhibited
      when eLCs were pretreated with a mAb to langerin CRD or when HIV was pretreated
      with a soluble langerin trimeric extracellular domain or by a CRD homolog.
      However, the langerin homolog did not inhibit direct HIV infection of T cells.
      These two novel soluble langerin inhibitors could be developed to prevent HIV
      uptake, infection, and subsequent transfer to T cells during early stages of
      infection. 

PMID- 25070851
TI  - The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-beta
      during Chlamydia trachomatis infection.
AB  - IFN-beta has been implicated as an effector of oviduct pathology resulting from
      genital chlamydial infection in the mouse model. In this study, we investigated
      the role of cytosolic DNA and engagement of DNA sensors in IFN-beta expression
      during chlamydial infection. We determined that three-prime repair exonuclease-1,
      a host 3' to 5' exonuclease, reduced IFN-beta expression significantly during
      chlamydial infection using small interfering RNA and gene knockout fibroblasts,
      implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic
      GMP-AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic
      GMP-AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to
      induce IFN-beta expression. We determined that cGAS is required for IFN-beta
      expression during chlamydial infection in multiple cell types. Interestingly,
      although infected cells deficient for STING or cGAS alone failed to induce IFN
      beta, coculture of cells depleted for either STING or cGAS rescued IFN-beta
      expression. These data demonstrate that cyclic GMP-AMP produced in infected
      cGAS(+)STING(-) cells can migrate into adjacent cells via gap junctions to
      function in trans in cGAS(-)STING(+) cells. Furthermore, we observed cGAS
      localized in punctate regions on the cytosolic side of the chlamydial inclusion
      membrane in association with STING, indicating that chlamydial DNA is most likely
      recognized outside the inclusion as infection progresses. These novel findings
      provide evidence that cGAS-mediated DNA sensing directs IFN-beta expression
      during Chlamydia trachomatis infection and suggest that effectors from infected
      cells can directly upregulate IFN-beta expression in adjacent uninfected cells
      during in vivo infection, contributing to pathogenesis. 

PMID- 25070853
TI  - Cutting edge: generation of effector cells that localize to mucosal tissues and
      form resident memory CD8 T cells is controlled by mTOR.
AB  - Mucosal tissues are subject to frequent pathogen exposure and are major sites for
      transmission of infectious disease. CD8 T cells play a critical role in
      controlling mucosa-acquired infections even though their migration into mucosal
      tissues is tightly regulated. The mechanisms and signals that control the
      formation of tissue-resident memory CD8 T cells are poorly understood; however,
      one key regulator of memory CD8 T cell differentiation, mammalian target of
      rapamycin kinase, can be inhibited by rapamycin. We report that, despite
      enhancing the formation of memory CD8 T cells in secondary lymphoid tissues,
      rapamycin inhibits the formation of resident memory CD8 T cells in the intestinal
      and vaginal mucosa. The ability of rapamycin to block the formation of functional
      resident CD8 T cells in mucosal tissues protected mice from a model of CD8 T cell
      mediated lethal intestinal autoimmunity. These findings demonstrate an opposing
      role for mammalian target of rapamycin in the formation of resident versus
      nonresident CD8 T cell immunity. 

PMID- 25070852
TI  - Specific increase in potency via structure-based design of a TCR.
AB  - Adoptive immunotherapy with Ag-specific T lymphocytes is a powerful strategy for
      cancer treatment. However, most tumor Ags are nonreactive "self" proteins, which
      presents an immunotherapy design challenge. Recent studies have shown that tumor
      specific TCRs can be transduced into normal PBLs, which persist after transfer in
      ~30% of patients and effectively destroy tumor cells in vivo. Although
      encouraging, the limited clinical responses underscore the need for enrichment of
      T cells with desirable antitumor capabilities prior to patient transfer. In this
      study, we used structure-based design to predict point mutations of a TCR (DMF5)
      that enhance its binding affinity for an agonist tumor Ag-MHC (peptide-MHC
      [pMHC]), Mart-1 (27L)-HLA-A2, which elicits full T cell activation to trigger
      immune responses. We analyzed the effects of selected TCR point mutations on T
      cell activation potency and analyzed cross-reactivity with related Ags. Our
      results showed that the mutated TCRs had improved T cell activation potency while
      retaining a high degree of specificity. Such affinity-optimized TCRs have
      demonstrated to be very specific for Mart-1 (27L), the epitope for which they
      were structurally designed. Although of somewhat limited clinical relevance,
      these studies open the possibility for future structural-based studies that could
      potentially be used in adoptive immunotherapy to treat melanoma while avoiding
      adverse autoimmunity-derived effects. 

PMID- 25070854
TI  - Bcl-xL regulates CD1d-mediated antigen presentation to NKT cells by altering CD1d
      trafficking through the endocytic pathway.
AB  - NKT cells are a unique subset of T cells that recognize glycolipid Ags presented
      in the context of CD1d molecules. NKT cells mount strong antitumor responses and
      are a major focus in developing effective cancer immunotherapy. It is known that
      CD1d molecules are constantly internalized from the cell surface, recycled
      through the endocytic compartments, and re-expressed on the cell surface.
      However, little is known about the regulation of CD1d-mediated Ag processing and
      presentation in B cell lymphoma. Prosurvival factors of the Bcl-2 family, such as
      Bcl-xL, are often upregulated in B cell lymphomas and are intimately linked to
      sphingolipid metabolism, as well as the endocytic compartments. We hypothesized
      that Bcl-xL can regulate CD1d-mediated Ag presentation to NKT cells. We found
      that overexpression or induction of Bcl-xL led to increased Ag presentation to
      NKT cells. Conversely, the inhibition or knockdown of Bcl-xL led to decreased NKT
      cell activation. Furthermore, knockdown of Bcl-xL resulted in the loss of CD1d
      trafficking to lysosome-associated membrane protein 1(+) compartments. Rab7, a
      late endosomal protein, was upregulated and CD1d molecules accumulated in the
      Rab7(+) late endosomal compartment. These results demonstrate that Bcl-xL
      regulates CD1d-mediated Ag processing and presentation to NKT cells by altering
      the late endosomal compartment and changing the intracellular localization of
      CD1d. 

PMID- 25070855
TI  - Collaboration between a soluble C-type lectin and calreticulin facilitates white
      spot syndrome virus infection in shrimp.
AB  - White spot syndrome virus (WSSV) mainly infects crustaceans through the digestive
      tract. Whether C-type lectins (CLs), which are important receptors for many
      viruses, participate in WSSV infection in the shrimp stomach remains unknown. In
      this study, we orally infected kuruma shrimp Marsupenaeus japonicus to model the
      natural transmission of WSSV and identified a CL (designated as M. japonicus
      stomach virus-associated CL [MjsvCL]) that was significantly induced by virus
      infection in the stomach. Knockdown of MjsvCL expression by RNA interference
      suppressed the virus replication, whereas exogenous MjsvCL enhanced it. Further
      analysis by GST pull-down and coimmunoprecipitation showed that MjsvCL could bind
      to viral protein 28, the most abundant and functionally relevant envelope protein
      of WSSV. Furthermore, cell-surface calreticulin was identified as a receptor of
      MjsvCL, and the interaction between these proteins was a determinant for the
      viral infection-promoting activity of MjsvCL. The MjsvCL-calreticulin pathway
      facilitated virus entry likely in a cholesterol-dependent manner. This study
      provides insights into a mechanism by which soluble CLs capture and present
      virions to the cell-surface receptor to facilitate viral infection. 

PMID- 25070857
TI  - Unravelling India's tobacco epidemic--priorities and recommendations for the
      second round of Global Adult Tobacco Survey (GATS).
AB  - The Global Adult Tobacco Survey, or GATS, has proved to be an invaluable tool for
      policymakers. In India, it highlighted the alarming rates of prevalence of use
      and risks both nationally and at state level. However, a rapid analysis of GATS
      India shows that there are limitations in methods (sampling, questionnaire,
      measures undertaken to ensure data quality and management), which may impact the
      estimates of prevalence. This review discusses these potential weaknesses and
      recommends measures that can be adopted in the next round of surveys to overcome
      the limitations. 

PMID- 25070858
TI  - The glycation gap and estimated glomerular filtration rate in individuals without
      diabetes mellitus.

PMID- 25070856
TI  - Essential role for the lectin pathway in collagen antibody-induced arthritis
      revealed through use of adenovirus programming complement inhibitor MAp44
      expression.
AB  - Previous studies using mannose-binding lectin (MBL) and complement C4-deficient
      mice have suggested that the lectin pathway (LP) is not required for the
      development of inflammatory arthritis in the collagen Ab-induced arthritis (CAIA)
      model. MBL, ficolins and collectin-11 are key LP pattern recognition molecules
      that associate with three serine proteases-MASP-1, MASP-2, and MASP-3-and with
      two MBL-associated proteins designated sMAP and MBL-associated protein of 44kDA
      (MAp44). Recent studies have shown that MAp44, an alternatively spliced product
      of the MASP-1/3 gene, is a competitive inhibitor of the binding of the
      recognition molecules to all three MASPs. In these studies, we examined the
      effect of treatment of mice with adenovirus (Ad) programmed to express human
      MAp44 (AdhMAp44) on the development of CAIA. AdhMAp44 and Ad programming GFP
      (AdGFP) expression were injected i.p. in C57BL/6 wild type mice prior to the
      induction of CAIA. AdhMAp44 significantly reduced the clinical disease activity
      (CDA) score by 81% compared with mice injected with AdGFP. Similarly,
      histopathologic injury scores for inflammation, pannus, cartilage and bone
      damage, as well as C3 deposition in the cartilage and synovium, were
      significantly reduced by AdhMAp44 pretreatment. Mice treated with AdmMAp44,
      programming expression of mouse MAp44, also showed significantly decreased CDA
      score and histopathologic injury scores. In addition, administration of AdhMAp44
      significantly diminished the severity of Ross River virus-induced arthritis, an
      LP-dependent model. Our study provides conclusive evidence that an intact
      complement LP is essential to initiate CAIA, and that MAp44 may be an appropriate
      treatment for inflammatory arthritis. 

PMID- 25070859
TI  - Serotonergic modulation of pain and analgesic responses: a study in rats with
      constitutionally altered serotonin transporters.
AB  - BACKGROUND: A role of the serotonin (5HT) transporter, a key regulator of
      serotonergic transmission, in the physiology, pharmacology and genetics of pain
      responses has been proposed recently. The present study aimed to explore the
      impact of constitutive differences in the activity of the serotonin transporter,
      and 5HT homeostasis in general, on the modulation on pain sensitivity and
      analgesic responses to drugs that utilize 5HT mechanisms. METHODS: A novel
      genetic animal model, Wistar-Zagreb 5HT rats, obtained by selective breeding of
      animals for extreme activity of the platelet serotonin transporter was used. As a
      consequence of breeding, two sublines of this model, termed high-5HT and low-5HT,
      differ in both central and peripheral serotonin homeostasis. Thermal pain
      sensitivity of 5HT sublines was assessed at baseline and following administration
      of analgesic drugs, as determined by paw withdrawal latency to radiant heat
      stimulation. RESULTS: Animals from 5HT sublines show differences in both basal
      pain sensitivity and analgesic responses. Rats with the low-5HT phenotype
      displayed decreased baseline paw withdrawal latencies (hyperalgesia) in
      comparison to their high-5HT counterpart (25%; p < 0.001). They also showed
      better analgesic response to acute and prolonged treatment with tramadol (p =
      0.027) and clomipramine (p = 0.019), respectively, whereas administration of
      fluvoxamine did not produce an analgesic effect in either 5HT subline.
      CONCLUSIONS: These findings support the idea that functionality of the serotonin
      transporter is one of the physiological/genetic determinants of individual
      differences in pain responses and modulation. They also validate Wistar-Zagreb
      5HT rats, with constitutionally up-regulated/down-regulated serotonin
      transporter, as a potential new genetic model for studying serotonergic
      modulation of pain responses.

PMID- 25070860
TI  - Sickle cell disease in mice is associated with sensitization of sensory nerve
      fibers.
AB  - The pain phenotype in sickle cell disease (SCD) patients is highly variable. A
      small percentage of SCD patients experience many vaso-occlusive crises/year, 5%
      of patients account for over 30% of pain episodes, while 39% report few episodes
      of severe pain. Clearly, a better understanding of the pathobiology of SCD is
      needed to improve its therapy. Humanized sickle cell mice recapitulate several
      phenotypes of SCD patients and provide a model for the study of SCD pain.
      Researchers have shown that one strain of humanized SCD mice, the BERK strain,
      has abnormal pain phenotype. However, the nociception phenotype of another
      humanized SCD mouse strain, the Townes strain, has not been described. In a large
      cross-sectional study of BERK and Townes SCD mice, we examined thermosensory
      response and sensory nerve fiber function using sine-wave electrical stimulation
      at 2000, 250, and 5 Hz to stimulate preferentially Abeta, Adelta, and C sensory
      nerve fibers, respectively. We found that BERK and Townes mice, compared to
      respective controls, had decreases in 2000, 250, and 5 Hz current vocalization
      thresholds in patterns that suggest sensitization of a broad spectrum of sensory
      nerve fibers. In addition, the pattern of sensitization of sensory fibers varied
      according to strain, sex, age, and mouse genotype. In a similarly variable
      pattern, Townes and BERKs also had significantly altered sensitivity to noxious
      thermal stimuli in agreement with what has been shown by others. In summary, the
      analysis of somatosensory function using sine-wave electrical stimulation in
      humanized sickle cell mice suggests that in SCD, both myelinated and
      unmyelinated, fibers are sensitized. The pattern of sensory fiber sensitization
      is distinct from that observed in pain models of neuropathic and inflammatory
      pain. These findings raise the possibility that sensitization of a broad spectrum
      of sensory fibers might contribute to the altered and variable nociception
      phenotype in SCD. 

PMID- 25070861
TI  - Administering anticipatory medications in end-of-life care: a qualitative study
      of nursing practice in the community and in nursing homes.
AB  - BACKGROUND: In the United Kingdom, an approach to improving end-of-life care has
      been the introduction of 'just in case' or 'anticipatory' medications. Nurses are
      often responsible for deciding when to use anticipatory medications, but little
      is known about their experiences. AIM: To examine nurses' decisions, aims and
      concerns when using anticipatory medications. DESIGN: An ethnographic study in
      two UK regions, using observations and interviews with nurses working in
      community and nursing home teams (n = 8). FINDINGS: Observations (n = 83) and
      interviews (n = 61) with community nurses. Nurses identified four 'conditions'
      that needed to be established before they implemented anticipatory medications:
      (1) irreversibility; (2) inability to take oral medication; (3) where the patient
      was able, they should consent and (4) decision had to be independent of demands
      or requests from patient's relatives. By using anticipation medications, nurses
      sought to enable patients to be 'comfortable and settled' by provision of gradual
      relief of symptoms at the lowest dose possible. They aimed to respond quickly to
      needs, seeking to avoid hospital admission or medical call-out, while adhering to
      local prescribing policies. Worries included distinguishing between pain and
      agitation, balancing risks of under- and over-medication and the possibility of
      hastening death. CONCLUSION: Nurses take a leading role in the administration of
      anticipatory medications. Nurses apply consideration and caution to the
      administration of anticipatory medications but some experience emotional burden.
      Education, training and experience played a role in the nurses' confidence and
      should continue to be central to efforts to improving the quality of palliative
      care in the community and nursing homes.

PMID- 25070862
TI  - Calcification in a changing ocean: perspectives on a virtual symposium in the
      biological bulletin.

PMID- 25070863
TI  - Fate of calcifying tropical symbiont-bearing large benthic foraminifera: living
      sands in a changing ocean.
AB  - Concerns regarding the response of calcifiers in future warmer and more acidic
      oceans have been raised in many studies. Tropical large benthic foraminifera
      (LBF) are important carbonate producers that reside in coral reefs worldwide.
      Similar to corals, these organisms live in symbioses with microalgae, which
      promote high calcification rates. The contribution of LBFs to reef sediments is
      under threat due to climate change. In this review, we synthesize research
      conducted on the effects of increased temperature and acidification on these
      organisms, and assess the potential impacts on reef carbonate production. A meta
      analysis of all available experimental data (18 publications, 84 individual
      experiments) on the effects of ocean warming and acidification on LBF holobiont
      health was performed using log-transformed response ratios (LnRR) comparing
      present-day ambient and projected future scenarios. For the latter, we used
      Representative Concentration Pathway 8.5 from the Intergovernmental Panel on
      Climate Change, which projects changes of +4  degrees C and -0.3 pH units by the
      year 2100. Overall, a general negative trend on holobiont growth was observed
      across most species of LBFs in response to both stressors. The only exception was
      the hyaline species (porous CaCO3 test composed of interlocking microcrystals)
      that have diatom symbionts. Species in this group appear resilient to future
      ocean acidification scenarios. Differences in the response of LBF species to
      warming and acidifying oceans may be due to (1) differences in the carbonate
      species' use in formation of the CaCO3 skeleton (CO2 vs. CO3(2-)), (2) varied
      responses of the symbiont types (diatom, dinoflagellate, rhodophyte) to
      stressors, or (3) the degree of nutritional dependence of the host to its
      symbiont. We also summarize current estimates of carbonate production by LBFs to
      provide a context of their contribution to reefs. Finally, we outline major gaps
      in knowledge in addressing the potential for LBF species persistence in a
      changing ocean.

PMID- 25070864
TI  - Perspectives on massive coral growth rates in a changing ocean.
AB  - The tropical ocean environment is changing at an unprecedented rate, with warming
      and severe tropical cyclones creating obvious impacts to coral reefs within the
      last few decades and projections of acidification raising concerns for the future
      of these iconic and economically important ecosystems. Documenting variability
      and detecting change in global and regional climate relies upon high-quality
      observational records of climate variables supplemented, prior to the mid-19th
      century, with reconstructions from various sources of proxy climate information.
      Here we review how annual density banding patterns that are recorded in the
      skeletons of massive reef-building corals have been used to document
      environmental change and impacts within coral reefs. Massive corals provide a
      historical perspective of continuous calcification processes that pre-date most
      ecological observations of coral reefs. High-density stress bands, abrupt
      declines in annual linear extension, and evidence of partial mortality within the
      skeletal growth record reveal signatures of catastrophic stress events that have
      recently been attributed to mass bleaching events caused by unprecedented thermal
      stress. Comparison of recent trends in annual calcification with century-scale
      baseline calcification rates reveals that the frequency of growth anomalies has
      increased since the late 1990s throughout most of the world's coral reef
      ecosystems. Continuous coral growth histories provide valuable retrospective
      information on the coral response to environmental change and the consequences of
      anthropogenic climate change. Co-ordinated efforts to synthesize and combine
      global calcification histories will greatly enhance our understanding of current
      calcification responses to a changing ocean. 

PMID- 25070865
TI  - Growth and calcification of marine bryozoans in a changing ocean.
AB  - Bryozoans are colonial benthic marine invertebrate calcifiers, important and
      especially abundant and diverse in southern hemisphere shelf environments. Large
      heavily calcified colonies can be up to 50 years old, but most longer-lived
      bryozoans are limited to 10-20 y. Many smaller species are annual. Radial
      extension in flat encrusting bryozoans is generally on the order of 1-5 mm/y.
      Erect calcified species generally grow vertically 2-15 mm/y, though articulated
      species such as Cellaria may reach rates of 40 mm/y. Corresponding calcification
      rates are generally 10(1)-10(2) mg/y, but there can be an order of magnitude
      variation in rate among years in high-latitude bryozoans. Multi-branched
      bryozoans produce up to 24 g of CaCO3/y. The carbonate produced by bryozoans
      varies from calcite to aragonite and mixtures of both. Skeletal carbonate
      mineralogy of bryozoans is complex and appears to be strongly genetically
      controlled. Global climate change, leading to increasing water temperatures, will
      generally increase marine bryozoan metabolic rates, and may increase Mg in
      calcite. On the other hand, decreasing pH (ocean acidification) causes corrosion,
      changes in mineralogy, and decreased survival. This review of bryozoan growth and
      calcification allows a general perspective, but also reveals gaps in our
      knowledge which need to be addressed. 

PMID- 25070866
TI  - Predicting the effects of ocean acidification on predator-prey interactions: a
      conceptual framework based on coastal molluscs.
AB  - The influence of environmental change on species interactions will affect
      population dynamics and community structure in the future, but our current
      understanding of the outcomes of species interactions in a high-CO2 world is
      limited. Here, we draw upon emerging experimental research examining the effects
      of ocean acidification on coastal molluscs to provide hypotheses of the potential
      impacts of high-CO2 on predator-prey interactions. Coastal molluscs, such as
      oysters, mussels, and snails, allocate energy among defenses, growth, and
      reproduction. Ocean acidification increases the energetic costs of physiological
      processes such as acid-base regulation and calcification. Impacted molluscs can
      display complex and divergent patterns of energy allocation to defenses and
      growth that may influence predator-prey interactions; these include changes in
      shell properties, body size, tissue mass, immune function, or reproductive
      output. Ocean acidification has also been shown to induce complex changes in
      chemoreception, behavior, and inducible defenses, including altered cue detection
      and predator avoidance behaviors. Each of these responses may ultimately alter
      the susceptibility of coastal molluscs to predation through effects on predator
      handling time, satiation, and search time. While many of these effects may
      manifest as increases in per capita predation rates on coastal molluscs, the
      ultimate outcome of predator-prey interactions will also depend on how ocean
      acidification affects the specified predators, which also exhibit complex
      responses to ocean acidification. Changes in predator-prey interactions could
      have profound and unexplored consequences for the population dynamics of coastal
      molluscs in a high-CO2 ocean. 

PMID- 25070867
TI  - The skeleton of postmetamorphic echinoderms in a changing world.
AB  - Available evidence on the impact of acidification and its interaction with
      warming on the skeleton of postmetamorphic (juvenile and adult) echinoderms is
      reviewed. Data are available on sea urchins, starfish, and brittle stars in 33
      studies. Skeleton growth of juveniles of all sea urchin species studied so far is
      affected from pH 7.8 to 7.6 in seawater, values that are expected to be reached
      during the 21st century. Growth in adult sea urchins (six species studied) is
      apparently only marginally affected at seawater pH relevant to this century. The
      interacting effect of temperature differed according to studies. Juvenile
      starfish as well as adults seem to be either not impacted or even boosted by
      acidification. Brittle stars show moderate effects at pH below or equal to 7.4.
      Dissolution of the body wall skeleton is unlikely to be a major threat to sea
      urchins. Spines, however, due to their exposed position, are more prone to this
      threat, but their regeneration abilities can probably ensure their maintenance,
      although this could have an energetic cost and induce changes in resource
      allocation. No information is available on skeleton dissolution in starfish, and
      the situation in brittle stars needs further assessment. Very preliminary
      evidence indicates that mechanical properties in sea urchins could be affected.
      So, although the impact of ocean acidification on the skeleton of echinoderms has
      been considered as a major threat from the first studies, we need a better
      understanding of the induced changes, in particular the functional consequences
      of growth modifications and dissolution related to mechanical properties. It is
      suggested to focus studies on these aspects. 

PMID- 25070868
TI  - Effects of seawater acidification on gene expression: resolving broader-scale
      trends in sea urchins.
AB  - Sea urchins are ecologically and economically important calcifying organisms
      threatened by acidification of the global ocean caused by anthropogenic CO2
      emissions. Propelled by the sequencing of the purple sea urchin
      (Strongylocentrotus purpuratus) genome, profiling changes in gene expression
      during exposure to high pCO2 seawater has emerged as a powerful and increasingly
      common method to infer the response of urchins to ocean change. However, analyses
      of gene expression are sensitive to experimental methodology, and comparisons
      between studies of genes regulated by ocean acidification are most often made in
      the context of major caveats. Here we perform meta-analyses as a means of
      minimizing experimental discrepancies and resolving broader-scale trends
      regarding the effects of ocean acidification on gene expression in urchins.
      Analyses across eight studies and four urchin species largely support prevailing
      hypotheses about the impact of ocean acidification on marine calcifiers. The
      predominant expression pattern involved the down-regulation of genes within
      energy-producing pathways, a clear indication of metabolic depression. Genes with
      functions in ion transport were significantly over-represented and are most
      plausibly contributing to intracellular pH regulation. Expression profiles
      provided extensive evidence for an impact on biomineralization, epitomized by the
      down-regulation of seven spicule matrix proteins. In contrast, expression
      profiles provided limited evidence for CO2-mediated developmental delay or
      induction of a cellular stress response. Congruence between studies of gene
      expression and the ocean acidification literature in general validates the
      accuracy of gene expression in predicting the consequences of ocean change and
      justifies its continued use in future studies. 

PMID- 25070869
TI  - Effects of ocean acidification on population dynamics and community structure of
      crustose coralline algae.
AB  - Calcification and growth of crustose coralline algae (CCA) are affected by
      elevated seawater pCO2 and associated changes in carbonate chemistry. However,
      the effects of ocean acidification (OA) on population and community-level
      responses of CCA have barely been investigated. We explored changes in community
      structure and population dynamics (size structure and reproduction) of CCA in
      response to OA. Recruited from an experimental flow-through system, CCA settled
      onto the walls of plastic aquaria and developed under exposure to one of three
      pCO2 treatments (control [present day, 389+/-6 ppm CO2], medium [753+/-11 ppm],
      and high [1267+/-19 ppm]). Elevated pCO2 reduced total CCA abundance and affected
      community structure, in particular the density of the dominant species
      Pneophyllum sp. and Porolithon onkodes. Meanwhile, the relative abundance of P.
      onkodes declined from 24% under control CO2 to 8.3% in high CO2 (65% change),
      while the relative abundance of Pneophyllum sp. remained constant. Population
      size structure of P. onkodes differed significantly across treatments, with fewer
      larger individuals under high CO2. In contrast, the population size structure and
      number of reproductive structures (conceptacles) per crust of Pneophyllum sp. was
      similar across treatments. The difference in the magnitude of the response of
      species abundance and population size structure between species may have the
      potential to induce species composition changes in the future. These results
      demonstrate that the impacts of OA on key coral reef builders go beyond declines
      in calcification and growth, and suggest important changes to aspects of
      population dynamics and community ecology.

PMID- 25070870
TI  - Populations of Pacific oysters Crassostrea gigas respond variably to elevated CO2
      and predation by Morula marginalba.
AB  - Ocean acidification is anticipated to decrease calcification and increase
      dissolution of shelled molluscs. Molluscs with thinner and weaker shells may be
      more susceptible to predation, but not all studies have measured negative
      responses of molluscs to elevated pCO2. Recent studies measuring the response of
      molluscs have found greater variability at the population level than first
      expected. Here we investigate the impact of acidification on the predatory whelk
      Morula marginalba and genetically distinct subpopulations of the Pacific oyster
      Crassostrea gigas. Whelks and eight family lines of C. gigas were separately
      exposed to ambient (385 ppm) and elevated (1000 ppm) pCO2 for 6 weeks. Following
      this period, individuals of M. marginalba were transferred into tanks with
      oysters at ambient and elevated pCO2 for 17 days. The increase in shell height of
      the oysters was on average 63% less at elevated compared to ambient pCO2. There
      were differences in shell compression strength, thickness, and mass among family
      lines of C. gigas, with sometimes an interaction between pCO2 and family line.
      Against expectations, this study found increased shell strength in the prey and
      reduced shell strength in the predator at elevated compared to ambient pCO2.
      After 10 days, the whelks consumed significantly more oysters regardless of
      whether C. gigas had been exposed to ambient or elevated CO2, but this was not
      dependent on the family line and the effect was not significant after 17 days.
      Our study found an increase in predation after exposure of the predator to
      predicted near-future levels of estuarine pCO2. 

PMID- 25070871
TI  - Decline in coccolithophore diversity and impact on coccolith morphogenesis along
      a natural CO2 gradient.
AB  - A natural pH gradient caused by marine CO2 seeps off Vulcano Island (Italy) was
      used to assess the effects of ocean acidification on coccolithophores, which are
      abundant planktonic unicellular calcifiers. Such seeps are used as natural
      laboratories to study the effects of ocean acidification on marine ecosystems,
      since they cause long-term changes in seawater carbonate chemistry and pH,
      exposing the organisms to elevated CO2 concentrations and therefore mimicking
      future scenarios. Previous work at CO2 seeps has focused exclusively on benthic
      organisms. Here we show progressive depletion of 27 coccolithophore species, in
      terms of cell concentrations and diversity, along a calcite saturation gradient
      from Omegacalcite 6.4 to <1. Water collected close to the main CO2 seeps had the
      highest concentrations of malformed Emiliania huxleyi. These observations add to
      a growing body of evidence that ocean acidification may benefit some algae but
      will likely cause marine biodiversity loss, especially by impacting calcifying
      species, which are affected as carbonate saturation falls. 

PMID- 25070873
TI  - Fabric-based integrated energy devices for wearable activity monitors.
AB  - A wearable fabric-based integrated power-supply system that generates energy
      triboelectrically using human activity and stores the generated energy in an
      integrated supercapacitor is developed. This system can be utilized as either a
      self-powered activity monitor or as a power supply for external wearable sensors.
      These demonstrations give new insights for the research of wearable electronics. 

PMID- 25070874
TI  - IgG sera levels against a subset of periodontopathogens and severity of disease
      in aggressive periodontitis patients: a cross-sectional study of selected pocket
      sites.
AB  - AIMS: To evaluate the association among serum immunoglobulin G (IgG) responses to
      Aggregatibacter actinomycetemcomitans (Aa) serotypes a, b and c, Porphyromonas
      gingivalis (Pg), Tannerella forsythia (Tf) and clinical parameters in Aggressive
      Periodontitis (AP) subjects. Associations between periodontal pathogens and
      clinical and immunological parameters were also evaluated. METHODS: Thirty-eight
      subjects diagnosed with generalized AP (GAP) and localized AP (LAP) were
      included. Ten healthy controls were also evaluated. Clinical parameters were
      assessed and percentages of subgingival levels of Aa, Pg and Tf (beyond bacterial
      load), were determined by quantitative real-time polymerase chain reaction. Serum
      IgG antibody levels against Aa, Pg and Tf were evaluated by enzyme-linked
      immunosorbent assay. RESULTS: Percentages of Aa, Pg and Tf were significantly
      higher in AP than in controls. The response to Aa serotype c was higher in LAP
      subjects than in controls. There were no differences in microbial composition or
      antibodies responses between GAP and LAP, except for IgG response to Tf. Pg
      levels were correlated with probing depth (PD), BoP and CAL in GAP but not in LAP
      subjects. Tf levels correlated with PD and CAL in GAP subjects. In GAP, the
      infection levels of Aa and Pg correlated with the corresponding IgG levels to Aa
      serotype c and Pg. CONCLUSION: Given the evidences that IgG response in AP
      patients correlated with bacterial infection level in GAP, but not in LAP, and
      that LAP patients lack a response to Tf, despite harbouring this species, our
      data suggest a difference in host immune defence between these two forms of
      aggressive periodontitis.

PMID- 25070876
TI  - Utility of FDG-PET in primary renal lymphoma.

PMID- 25070875
TI  - Effects of cell-type-specific expression of a pan-caspase inhibitor on renal
      fibrogenesis.
AB  - BACKGROUND: The caspase family of enzymes is grouped into two major sub-families,
      namely apoptotic and inflammatory caspases, which play central roles in the
      induction of apoptosis, regulation of inflammation and immunity, and cellular
      differentiation. METHODS: The role of caspase activation in tubular epithelium
      and interstitial cells of 3 lines of transgenic mice with obstructed nephropathy
      was examined: p35 mice bearing the pan-caspase inhibitor protein expressed by the
      p35 gene separated from the universal CAG promoter by a floxed STOP sequence were
      crossed with gammaGT.Cre and FSP1.Cre mice that express Cre recombinase in the
      cortical tubular epithelium and FSP1(+) interstitial cells, respectively. The
      gammaGT.Cre;p35, FSP1.Cre;p35 and p35 control mice were then challenged with
      unilateral ureter obstruction (UUO). RESULTS: Proinflammatory parameters such as
      protein levels of active IL-1beta subunit and mRNA levels of TNF-alpha and NOD
      like receptor pyrin domain containing-3, and profibrogenic parameters such as
      interstitial matrix deposition and mRNA levels of fibronectin EIIIA isoform and
      alpha1 chain of procollagen type I in the kidneys were significantly increased at
      7 days in the FSP1.Cre;p35- and p35-UUO mice, but not in the gammaGT.Cre;p35-UUO
      mice. These changes paralleled the numbers of apoptotic nuclei in tubules, but
      not in interstitial cells, and the protein levels of active caspase-3 subunit in
      the kidneys of FSP1.Cre;p35-, p35- and gammaGT.Cre;p35-UUO mice. CONCLUSION: This
      study provides evidence of the critical role of caspase activation in the tubular
      epithelium, but not in FSP1(+) interstitial cells, in apoptosis and inflammasome
      induction, leading to proinflammatory and profibrogenic processes in fibrous
      kidneys with UUO.

PMID- 25070879
TI  - Cysteine-selective reactions for antibody conjugation.
AB  - Moving tracks from maleimide: New site-selective protein modification reactions
      at cysteine have been developed. Unlike conventional maleimide conjugation, which
      results in a labile thioether succinimide, the new bioconjugation reactions
      result in stable conjugates and provide opportunities to develop a new generation
      of homogeneous, stable, and therapeutically useful conjugates. 

PMID- 25070878
TI  - Dyspnea as an independent predictor of mortality.
AB  - BACKGROUND AND AIM: Dyspnea is a common and easily elicited presenting complaint
      in patients seen by physicians who evaluate and take care of chronic respiratory
      disorders. Although dyspnea is subjective and tends to increase with age or
      reduced lung function, it appears to be reproducible as a symptom and often
      signifies serious underlying disease. METHODS: Systematic review of longitudinal
      studies with dyspnea as the exposure and mortality as the outcome; age, smoking
      and lung function had to be controlled for to be included in the review. In
      addition, a minimum sample size at baseline of 500 subjects was required for each
      study. RESULTS: From over 3000 potential references, 10 longitudinal studies met
      all criteria and were included. All 10 studies suggested that dyspnea was an
      independent predictor of mortality with point estimates by odds ratio, rate ratio
      or hazard ratios ranging from 1.3 up to 2.9-fold greater than baseline. All 10
      studies had actual or implied 95% confidence interval bands greater than the null
      value of one. CONCLUSION: Dyspnea, a symptom, predicts mortality and is a proxy
      for underlying diseases, most often of heart and lung. Therefore, chronic dyspnea
      needs to be evaluated as to etiology to allow for treatment to minimize morbidity
      and mortality when possible.

PMID- 25070877
TI  - Intestinal barrier dysfunction in HIV infection: pathophysiology, clinical
      implications and potential therapies.
AB  - INTRODUCTION: Current pathogenetic aspects on HIV infection highlight the
      importance of a chronic immune activation ultimately leading to T lymphocyte
      homeostasis disruption and immune deregulation associated with disease
      manifestations and progression. It is widely accepted that this continuous immune
      activation in HIV infection is principally driven by the phenomenon of
      pathological microbial translocation (MT). METHODS: Review of the literature on
      the role of intestinal barrier dysfunction in HIV infection, with emphasis on the
      implicated pathophysiological mechanisms, clinical implications and potentially
      effective therapeutic interventions. FINDINGS: MT in HIV infection is promoted by
      a multifactorial disruption of all major levels comprising the intestinal barrier
      defense. Specifically, HIV infection disrupts the integrity of the intestinal
      biological (quantitative and qualitative alterations of gut microecology,
      overgrowth of pathogenic bacteria), immune (depletion of CD4(+) T cells,
      especially Th17 cells, increased CD4+ FoxP3+ Tregs, decreased mucosal macrophages
      phagocytic capacity, development of intestinal proinflammatory milieu) and
      mechanical barrier (enterocytes' apoptosis, disruption of tight junctions).
      Intestinal barrier dysfunction allows the passage of microbes and
      immunostimulatory bioproducts from the gut lumen first in the lamina propria and
      thereafter in the systemic circulation, thus continuously promoting a local and
      systemic inflammatory response. This chronic immune activation is associated with
      HIV disease progression, suboptimal response to HAART and development of non-AIDS
      comorbidities. CONCLUSIONS: We have reached a point where the effective control
      of HIV viremia by HAART should be combined with emerging pharmacological
      approaches aiming at the restoration of the intestinal barrier, targeting its
      diverse levels of structure and function. Elimination of the MT phenomenon would
      mitigate its effect on immune homeostasis, which might improve the prognosis of
      the HIV-infected patient in terms of morbidity and mortality.

PMID- 25070880
TI  - Thank you for your lovely card: ethical considerations in responding to bereaved
      parents invited in error to participate in childhood cancer survivorship
      research.
AB  - Research exploring the needs of families of childhood cancer survivors is
      critical to improving the experiences of future families faced by this disease.
      However, there are numerous challenges in conducting research with this unique
      population, including a relatively high mortality rate. In recognition that
      research with cancer survivors is a relational activity, this article presents a
      series of cases of parents bereaved by childhood cancer who unintentionally
      received invitations to participate in survivorship research. We explore six
      ethical considerations, and compare our experiences with that described
      previously. Our considerations include the sharing of confidential information
      with external parties to confirm past patients' vital status and appropriate
      researcher responses to bereaved parents. The management of researchers'
      emotional safety when working with illness populations and the fact that study
      invitations can elicit grief responses in non-bereaved families are discussed. To
      conclude, we argue for the benefits of inviting bereaved parents whose children
      died after treatment completion in survivorship research. Such parents' early
      survivorship experiences will otherwise be systemically neglected. We argue that
      discussing complex cases can assist researchers to protect participants' and
      researchers' emotional well-being. We hope to contribute to the dearth of
      discussion about research operating procedures to address these issues. 

PMID- 25070882
TI  - Next time I'll ask.

PMID- 25070881
TI  - Institutional care and iron deficiency increase ADHD symptomology and lower IQ
      2.5-5 years post-adoption.
AB  - Increased ADHD symptomology and lower IQ have been reported in internationally
      adopted (IA) children compared to non-adopted peers (Hostinar, Stellern,
      Schaefer, Carlson & Gunnar, 2012; Kreppner, O'Connor & Rutter, 2001). However, it
      is unclear whether these outcomes are due to institutional deprivation
      specifically or to co-occurring micronutrient deficiencies that disrupt brain
      development (Fuglestad, Rao & Georgieff, 2008b). In this study, IA children were
      compared to children raised in their biological families to examine differences
      in ADHD symptomology and IQ 2.5-5 years post-adoption and to assess the
      contributions of iron deficiency (ID) and duration of deprivation to these
      cognitive outcomes. ADHD symptoms (parent- and experimenter-reported) and IQ were
      evaluated in 88 IA (M = 62.1 months, SD = 2.4) and 35 non-adopted children (M =
      61.4 months, SD = 1.6). IA children were assessed 29-64 months post-adoption (M =
      41.9 months, SD = 10.2). ID was assessed during the initial post-adoption medical
      visit in 69 children, and children were classified into four groups by iron
      status, ranging from normal to ID anemia (most severe). IA children had greater
      ADHD symptomology, p < .01, and lower IQ, p = .001, than non-adopted children.
      Within the IA group, children with more severe ID at adoption had greater ADHD
      symptomology, r(69) = 0.40, p = .001, and lower IQ, r(68) = -0.28, p < .05.
      Duration of institutional care was positively correlated with ADHD symptoms,
      r(86) = .28, p < .01, but not IQ, r(85) = -.08, p = .52. Longitudinal results
      indicate improvement in IQ from 12 months post-adoption to age 5 for children
      with greater ID severity at adoption and longer duration of institutional care
      but no improvement in ADHD symptoms. These results signify continuing effects of
      early deprivation and ID on ADHD symptoms and IQ years after adoption. A video
      abstract of this article can be viewed at
      http://www.youtube.com/watch?v=vUFDAS3DD1c.

PMID- 25070883
TI  - Molecular basis and zygosity determination of D variants including identification
      of four novel alleles in Chinese individuals.
AB  - BACKGROUND: The frequency and molecular basis of the D variants have been
      reported in the Caucasian and African populations, but relatively little
      information was known in the Chinese population. Here, a study was investigated
      in Chinese persons with weak or discrepant D serologic typing. STUDY DESIGN AND
      METHODS: D variant was typed with a serologic method. The full coding regions of
      RHD of these variants were amplified with polymerase chain reaction and then
      directly sequenced. RHD zygosity test was performed using the hybrid Rhesus box
      technique and a multiplex ligation-dependent probe amplification (MLPA) assay was
      also used to analyze the variant alleles and RHD gene copy number. RESULTS:
      Twelve distinct RHD mutation alleles were found in 32 D variant individuals, with
      eight weak D and four partial D alleles. Weak D Type 15 and DVI Type 3 were the
      major weak D and partial D alleles in Zhejiang Han persons. Three novel weak D
      alleles (RHD weak D 95A, 779G, and 670G) and one new partial D allele (RHD130-132
      del TCT) were identified. The results of RHD zygosity in three individuals
      disagreed between the RHD zygosity test and the MLPA assay. The most known
      variant alleles can be detected, but four novel alleles were missed using the RH
      MLPA assay. CONCLUSION: The molecular basis and zygosity of D variants in
      Zhejiang Han persons were analyzed, and four novel RHD alleles were identified.
      These data extend the information of D variants and may help to improve the
      transfusion strategy of the D variants.

PMID- 25070885
TI  - Capillary malformation in the lumbosacral region as a clinical sign of occult
      spinal dysraphism.

PMID- 25070886
TI  - A combination turbidity and supernatant microplate assay to rank-order the
      supersaturation limits of early drug candidates.
AB  - A unique opportunity exists at the drug discovery stage to overcome inherently
      poor solubility by selecting drug candidates with superior supersaturation
      propensity. Existing supersaturation assays compare either precipitation
      resistant or precipitation-inhibiting excipients, or higher-energy polymorphic
      forms, but not multiple compounds or multiple concentrations. Furthermore, these
      assays lack sufficient throughput and compound conservation necessary for
      implementation in the discovery environment. A microplate-based combination
      turbidity and supernatant concentration assay was therefore developed to
      determine the extent to which different compounds remain in solution as a
      function of applied concentration in biorelevant media over a specific period of
      time. Dimethyl sulfoxide stock solutions at multiple concentrations of four
      poorly soluble, weak base compounds (Dipyridamole, Ketoconazole, Albendazole, and
      Cinnarizine) were diluted with pH 6.5 buffer as well as FaSSIF. All samples were
      monitored for precipitation by turbidity at 600 nm over 1 h and the final
      supernatant concentrations were measured. The maximum supersaturation ratio was
      calculated from the supersaturation limit and the equilibrium solubility in each
      media. Compounds were rank-ordered by supersaturation ratio: Ketoconazole >
      Dipyridamole > Cinnarizine ~ Albendazole. These in vitro results correlated well
      with oral AUC ratios from published in vivo pH effect studies, thereby confirming
      the validity of this approach.

PMID- 25070887
TI  - Pyruvate kinase M2 in blood circulation facilitates tumor growth by promoting
      angiogenesis.
AB  - It is long known that pyruvate kinase isoform M2 (PKM2) is released into the
      circulation of cancer patients. The PKM2 levels in patients have been suggested
      as a diagnostic marker for many types of cancers. However, it is not known how
      PKM2 is released in the blood, and whether the circulating PKM2 has any
      physiological function(s) in tumor progression. In this report, we demonstrate
      that PKM2 in the blood facilitates tumor growth by promoting tumor angiogenesis.
      Our experiments show that PKM2 promotes tumor angiogenesis by increasing
      endothelial cell proliferation, migration, and cell-ECM adhesion. Only the
      dimeric PKM2 possess the activity in promoting tumor angiogenesis, which is
      consistent with the observations that PKM2 in circulation of cancer patients is a
      dimer form. 

PMID- 25070888
TI  - Src-mediated post-translational regulation of endoglin stability and function is
      critical for angiogenesis.
AB  - Endoglin is a transforming growth factor beta (TGF-beta) co-receptor essential
      for angiogenesis and tumor vascularization. Endoglin modulates the crucial
      balance between pro- and anti-angiogenic signaling by activin receptor-like
      kinase (ALK) 1, 5, and TGF-beta type II (TbetaRII) receptors. Despite its
      established role in physiology and disease, the mechanism of endoglin down
      regulation remains unknown. Here we report that the conserved juxtamembrane
      cytoplasmic tyrosine motif ((612)YIY(614)) is a critical determinant of
      angiogenesis. Src directly phosphorylates this motif to induce endoglin
      internalization and degradation via the lysosome. We identified epidermal growth
      factor (EGF) and vascular endothelial growth factor (VEGF) as Src-activators that
      induce endoglin turnover following (612)YIY(614) phosphorylation. Interestingly,
      Src phosphorylation of endoglin-(612)YIY(614) was also an important process for
      receptor down-regulation by TRACON105 (TRC105), an endoglin-targeting antibody
      currently in clinical trials. The regulation of (612)YIY(614) phosphorylation was
      critical for angiogenesis, as both the phosphomimetic and unphosphorylatable
      mutants impaired endothelial functions including proliferation, migration, and
      capillary tube formation. Collectively, these findings establish Src and pro
      angiogenic mitogens as critical mediators of endoglin stability and function. 

PMID- 25070889
TI  - Protein kinase Calpha (PKCalpha) regulates bone architecture and osteoblast
      activity.
AB  - Bones' strength is achieved and maintained through adaptation to load bearing.
      The role of the protein kinase PKCalpha in this process has not been previously
      reported. However, we observed a phenotype in the long bones of Prkca(-/-) female
      but not male mice, in which bone tissue progressively invades the medullary
      cavity in the mid-diaphysis. This bone deposition progresses with age and is
      prevented by disuse but unaffected by ovariectomy. Castration of male Prkca(-/-)
      but not WT mice results in the formation of small amounts of intramedullary bone.
      Osteoblast differentiation markers and Wnt target gene expression were up
      regulated in osteoblast-like cells derived from cortical bone of female Prkca(-/
      ) mice compared with WT. Additionally, although osteoblastic cells derived from
      WT proliferate following exposure to estradiol or mechanical strain, those from
      Prkca(-/-) mice do not. Female Prkca(-/-) mice develop splenomegaly and reduced
      marrow GBA1 expression reminiscent of Gaucher disease, in which PKC involvement
      has been suggested previously. From these data, we infer that in female mice,
      PKCalpha normally serves to prevent endosteal bone formation stimulated by load
      bearing. This phenotype appears to be suppressed by testicular hormones in male
      Prkca(-/-) mice. Within osteoblastic cells, PKCalpha enhances proliferation and
      suppresses differentiation, and this regulation involves the Wnt pathway. These
      findings implicate PKCalpha as a target gene for therapeutic approaches in low
      bone mass conditions. 

PMID- 25070890
TI  - Crystal structure of the cGMP-dependent protein kinase II leucine zipper and
      Rab11b protein complex reveals molecular details of G-kinase-specific
      interactions.
AB  - cGMP-dependent protein kinase (PKG)-interacting proteins (GKIPs) mediate cellular
      targeting of PKG isoforms by interacting with their leucine zipper (LZ) domains.
      These interactions prevent aberrant signaling cross-talk between different PKG
      isotypes. To gain detailed insight into isotype-specific GKIP recognition by PKG,
      we analyzed the type II PKG leucine zipper domain and found that residues 40-83
      dimerized and specifically interacted with Rab11b. Next, we determined a crystal
      structure of the PKG II LZ-Rab11b complex. The PKG II LZ domain presents a mostly
      nonpolar surface onto which Rab11b docks, through van der Waals interactions.
      Contact surfaces in Rab11b are found in switch I and II, interswitch, and the
      beta1/N-terminal regions. This binding surface dramatically differs from that
      seen in the Rab11 family of interacting protein complex structures. Structural
      comparison with PKG Ialpha and Ibeta LZs combined with mutagenic analysis reveals
      that GKIP recognition is mediated through surface charge interactions. 

PMID- 25070891
TI  - The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's
      chromatin localization.
AB  - Fanconi anemia is a genetic disease resulting in bone marrow failure, birth
      defects, and cancer that is thought to encompass a defect in maintenance of
      genomic stability. Mutations in 16 genes (FANCA, B, C, D1, D2, E, F, G, I, J, L,
      M, N, O, P, and Q) have been identified in patients, with the Fanconi anemia
      subtype J (FA-J) resulting from homozygous mutations in the FANCJ gene. Here, we
      describe the direct interaction of FANCD2 with FANCJ. We demonstrate the
      interaction of FANCD2 and FANCJ in vivo and in vitro by immunoprecipitation in
      crude cell lysates and from fractions after gel filtration and with baculovirally
      expressed proteins. Mutation of the monoubiquitination site of FANCD2 (K561R)
      preserves interaction with FANCJ constitutively in a manner that impedes proper
      chromatin localization of FANCJ. FANCJ is necessary for FANCD2 chromatin loading
      and focus formation in response to mitomycin C treatment. Our results suggest not
      only that FANCD2 regulates FANCJ chromatin localization but also that FANCJ is
      necessary for efficient loading of FANCD2 onto chromatin following DNA damage
      caused by mitomycin C treatment. 

PMID- 25070892
TI  - The angiotensin II type 1 receptor (AT1R) closely interacts with large
      conductance voltage- and Ca2+-activated K+ (BK) channels and inhibits their
      activity independent of G-protein activation.
AB  - Angiotensin II (ANG-II) and BK channels play important roles in the regulation of
      blood pressure. In arterial smooth muscle, ANG-II inhibits BK channels, but the
      underlying molecular mechanisms are unknown. Here, we first investigated whether
      ANG-II utilizes its type 1 receptor (AT1R) to modulate BK activity.
      Pharmacological, biochemical, and molecular evidence supports a role for AT1R. In
      renal arterial myocytes, the AT1R antagonist losartan (10 MUM) abolished the ANG
      II (1 MUM)-induced reduction of whole cell BK currents, and BK channels and ANG
      II receptors were found to co-localize at the cell periphery. We also found that
      BK inhibition via ANG-II-activated AT1R was independent of G-protein activation
      (assessed with 500 MUM GDPbetaS). In BK-expressing HEK293T cells, ANG-II (1 MUM)
      also induced a reduction of BK currents, which was contingent on AT1R expression.
      The molecular mechanisms of AT1R and BK channel coupling were investigated in co
      transfected cells. Co-immunoprecipitation showed formation of a macromolecular
      complex, and live immunolabeling demonstrated that both proteins co-localized at
      the plasma membrane with high proximity indexes as in arterial myocytes.
      Consistent with a close association, we discovered that the sole AT1R expression
      could decrease BK channel voltage sensitivity. Truncated BK proteins revealed
      that the voltage-sensing conduction cassette is sufficient for BK-AT1R
      association. Finally, C-terminal yellow and cyan fluorescent fusion proteins,
      AT1R-YFP and BK-CFP, displayed robust co-localized Forster resonance energy
      transfer, demonstrating intermolecular interactions at their C termini. Overall,
      our results strongly suggest that AT1R regulates BK channels through a close
      protein-protein interaction involving multiple BK regions and independent of G
      protein activation.

PMID- 25070893
TI  - The E3 deubiquitinase USP17 is a positive regulator of retinoic acid-related
      orphan nuclear receptor gammat (RORgammat) in Th17 cells.
AB  - Stable retinoic acid-related orphan nuclear receptor gammat (RORgammat)
      expression is pivotal for the development and function of Th17 cells. Here we
      demonstrate that expression of the transcription factor RORgammat can be
      regulated through deubiquitination, which prevents proteasome-mediated
      degradation. We establish that USP17 stabilizes RORgammat protein expression by
      reducing RORgammat polyubiquitination at its Lys-360 residue. In contrast,
      knockdown of endogenous USP17 in Th17 cells resulted in decreased RORgammat
      protein levels and down-regulation of Th17-related genes. Furthermore, USP17
      expression was up-regulated in CD4(+) T cells from systemic lupus erythematosus
      patients. Our data reveal a molecular mechanism in which RORgammat expression in
      Th17 cells can be positively regulated by USP17, thereby modulating Th17 cell
      functions. 

PMID- 25070894
TI  - Multiple regulatory mechanisms control the expression of the Geobacillus
      stearothermophilus gene for extracellular xylanase.
AB  - Geobacillus stearothermophilus T-6 produces a single extracellular xylanase
      (Xyn10A) capable of producing short, decorated xylo-oligosaccharides from the
      naturally branched polysaccharide, xylan. Gel retardation assays indicated that
      the master negative regulator, XylR, binds specifically to xylR operators in the
      promoters of xylose and xylan-utilization genes. This binding is efficiently
      prevented in vitro by xylose, the most likely molecular inducer. Expression of
      the extracellular xylanase is repressed in medium containing either glucose or
      casamino acids, suggesting that carbon catabolite repression plays a role in
      regulating xynA. The global transcriptional regulator CodY was shown to bind
      specifically to the xynA promoter region in vitro, suggesting that CodY is a
      repressor of xynA. The xynA gene is located next to an uncharacterized gene,
      xynX, that has similarity to the NIF3 (Ngg1p interacting factor 3)-like protein
      family. XynX binds specifically to a 72-bp fragment in the promoter region of
      xynA, and the expression of xynA in a xynX null mutant appeared to be higher,
      indicating that XynX regulates xynA. The specific activity of the extracellular
      xylanase increases over 50-fold during early exponential growth, suggesting cell
      density regulation (quorum sensing). Addition of conditioned medium to fresh and
      low cell density cultures resulted in high expression of xynA, indicating that a
      diffusible extracellular xynA density factor is present in the medium. The xynA
      density factor is heat-stable, sensitive to proteases, and was partially purified
      using reverse phase liquid chromatography. Taken together, these results suggest
      that xynA is regulated by quorum-sensing at low cell densities. 

PMID- 25070896
TI  - Commentary on: Assessing the safety of del Nido cardioplegia solution in adult
      congenital cases.

PMID- 25070897
TI  - Commentary on: Nanoparticle oxygen delivery to the ischemic heart.

PMID- 25070895
TI  - Mitochondria are gate-keepers of T cell function by producing the ATP that drives
      purinergic signaling.
AB  - T cells play a central role in host defense. ATP release and autocrine feedback
      via purinergic receptors has been shown to regulate T cell function. However, the
      sources of the ATP that drives this process are not known. We found that
      stimulation of T cells triggers a spike in cellular ATP production that doubles
      intracellular ATP levels in <30 s and causes prolonged ATP release into the
      extracellular space. Cell stimulation triggered rapid mitochondrial Ca(2+)
      uptake, increased oxidative phosphorylation, a drop in mitochondrial membrane
      potential (Deltapsim), and the accumulation of active mitochondria at the immune
      synapse of stimulated T cells. Inhibition of mitochondria with CCCP, KCN, or
      rotenone blocked intracellular ATP production, ATP release, intracellular Ca(2+)
      signaling, induction of the early activation marker CD69, and IL-2 transcription
      in response to cell stimulation. These findings demonstrate that rapid activation
      of mitochondrial ATP production fuels the purinergic signaling mechanisms that
      regulate T cells and define their role in host defense. 

PMID- 25070898
TI  - Extracorporeal membrane modality conversions.
AB  - We report the case of a patient with cardiovascular and respiratory failure due
      to severe anaphylaxis requiring multiple extracorporeal membrane oxygenation
      (ECMO) cannulation strategies to provide adequate oxygen delivery and ventilatory
      support during a period of rapid physiological change. ECMO provides partial or
      complete support of oxygenation-ventilation and circulation. The choice of which
      ECMO modality to use is governed by anatomical (vessel size, cardiovascular
      anatomy and previous surgeries) and physiological (respiratory and/or cardiac
      failure) factors. The urgency with which ECMO needs to be implemented (emergency
      cardiopulmonary resuscitation (eCPR), urgent, elective) and the institutional
      experience will also influence the type of ECMO provided. Here we describe a 12
      year-old schoolgirl who, having been resuscitated with peripheral veno-venous
      (VV) ECMO for severe hypoxemia due to status asthmaticus in the setting of acute
      anaphylaxis, required escalation to peripheral veno-arterial (VA) ECMO for
      precipitous cardiovascular deterioration. Insufficient oxygen delivery for
      adequate cellular metabolic function and possible cerebral hypoxia due to
      significant differential hypoxia necessitated ECMO modification. After six days
      of central (transthoracic) VA ECMO support and 21 days of intensive care unit
      (ICU) care, she made a complete recovery with no neurological sequelae. The use
      of ECMO support warrants careful consideration of the interplay of a patient's
      pathophysiology and extracorporeal circuit dynamics. Particular emphasis should
      be placed on the potential for mismatch between cardiovascular and respiratory
      support as well as the need to meet metabolic demands through adequate cerebral,
      coronary and systemic oxygenation. Cannulation strategies occasionally require
      alteration to meet and anticipate the patient's evolving needs. 

PMID- 25070899
TI  - Bicaval dual-lumen cannula for venovenous extracorporeal membrane oxygenation:
      Avalon(c) cannula in childhood disease.
AB  - Severe acute refractory respiratory failure is considered a life-threatening
      situation, with a high mortality of 40 to 60%. When conservative oxygenation
      methods fail, a lifesaving measure is the introduction of extracorporeal membrane
      oxygenation (ECMO). Venovenous ECMO (VV-ECMO) is a preferred modality of support
      for patients with refractory acute respiratory failure. Specifically, bicaval VV
      ECMO is a well-recognized and validated therapy, where single or double periphery
      venous access is used for the insertion of two differently sized cannulas in
      order to achieve adequate blood oxygenation. Compared to venoarterial ECMO, in VV
      ECMO, the rate of complications, such as thrombosis, bleeding, infection and
      ischemic events, is lower. On the other hand, the size and insertion location is
      an obstacle to patient mobilization. This is a considerable problem for patients
      where the time interval for lung recovery and the bridge to the transplantation
      is prolonged. To address this issue, a dual-lumen, single venovenous cannula was
      introduced. Here, by insertion of one single catheter in one target vessel, in a
      majority of cases in the right internal jugular vein, satisfactory oxygenation of
      the patient is achieved. In this form, the instituted VV-ECMO enables patient
      mobility, better physical rehabilitation and facilitates pulmonary extubation and
      toilet. However, relatively early, after the first short-term reports were
      published, a relatively high complication rate became evident. In the recent
      literature, the complication rate using actual commercially available double
      lumen venovenous cannula ranges between 5 and 30%. These cases were mostly
      conjoined to the implantation phase or the early postoperative phase and vary
      between right heart perforation to migration of the cannula. This review focuses
      on complications allied to commercially available dual-lumen, single, venovenous
      cannula implantation, pointing out the critical segments of the implantation
      process and analyzing the structure of the device. 

PMID- 25070900
TI  - Tibial rotational alignment was significantly improved by use of a CT-navigated
      control device in total knee arthroplasty.
AB  - This study compared the accuracy of three methods to set tibial component
      rotational alignment: (1) conventional method, the anteroposterior (AP) axis was
      determined by the surgeon using anatomical landmarks; (2) partial-navigation
      method, the tibia was prepared according to the AP axis using a CT-based
      navigation system and the component was manually positioned; (3) full-navigation
      method, the tibial component was positioned and fixed with cement under the
      control of navigation using a newly developed instrument. The conventional method
      showed considerable deviation (range, -18.6 degrees  to 14.7 degrees ), and the
      partial-navigation method also showed considerable deviation (-11.3 degrees  to
      8.1 degrees ). In contrast, the full-navigation method significantly improved the
      accuracy of alignment (-2.9 degrees  to 2.1 degrees ). The tibial component can
      become malaligned during cement fixation, even after proper bone preparation.

PMID- 25070901
TI  - Lateral patellar facetectomy and medial reefing in patients with lateral facet
      syndrome after patellar-retaining total knee arthroplasty.
AB  - We analyzed clinical outcomes of partial lateral patellar facetectomy and medial
      reefing in patients with lateral patellar facet syndrome with painful patellar
      retaining total knee arthroplasty. 34 patients were followed for a mean of 40
      months. All 34 patients were matched with those having secondary patellar
      resurfacing without facetectomy. Both groups experienced significant pain relief
      and range of motion improvement. The facetectomy group had higher Kujala scores
      than those in patellar resurfacing group. Patients with facetectomy had
      significantly less pain postoperatively. There were significant differences in
      postoperative lateral patellar tilt and congruency angle in both groups. The mid
      term results for LPF with medial reefing are promising to resolve pain in
      patients with lateral patellar facet syndrome in patellar-retaining TKA.
      Therapeutic level III (retrospective comparative study). 

PMID- 25070902
TI  - In reply: Total knee arthroplasty after lower extremity amputation: a review of
      13 cases.

PMID- 25070903
TI  - Identification of the critical residues for the function of vacuolar H+
      pyrophosphatase by mutational analysis based on the 3D structure.
AB  - H(+)-translocating pyrophosphatase (H(+)-PPase) converts energy from hydrolysis
      of inorganic pyrophosphate (PPi) to active H(+) translocation across membranes.
      From the 3D structure resolved by crystallography, 17 amino acid residues in
      several domains of mung bean (Vigna radiata) enzyme were selected and substituted
      with alanine individually. The mutant enzymes were expressed in yeast cells to
      evaluate their biochemical role. The highly conserved residues in the substrate
      binding site (T249, D269, D507 and N534) were shown to be essential for PPi
      hydrolysis and H(+) pump. The amino acid substitution of residues in the H(+)
      translocation pathway (I545, L555, N738, V746 and L749) resulted in mild decrease
      in the PPase activity and strong suppression of the H(+) pump. These results
      suggest that the decoupling of PPi hydrolysis and active H(+) translocation
      occurred in these five mutants including I545A. The alanine substitution of the
      C124 and C132, which form an intra-molecular disulfide bond, did not affect the
      enzyme activity. The modifications of the other residues in the vacuolar lumen
      loop, and M15 had relatively mild effect on the enzyme function. Functional roles
      of the 17 residues are discussed with consideration of the 3D structural
      information. 

PMID- 25070904
TI  - A tale of 2 capsules: retained capsule diagnosed by capsule endoscopy.

PMID- 25070905
TI  - Main duct intraductal papillary mucinous neoplasm presenting as a duodenal mass.

PMID- 25070906
TI  - Clues to uncommon and easily overlooked infectious diagnoses affecting the GI
      tract and distinction from their clinicopathologic mimics.

PMID- 25070907
TI  - Biodegradable stent placement before neoadjuvant chemoradiotherapy as a bridge to
      surgery in patients with locally advanced esophageal cancer.

PMID- 25070908
TI  - Early donor-specific antibodies in lung transplantation: risk factors and impact
      on survival.
AB  - BACKGROUND: The impact of early donor-specific anti-HLA antibodies (DSA) on
      patient and graft survival after lung transplantation remains controversial. In
      this study we analyzed risk factors for DSA that developed before initial
      hospital discharge after lung transplantation (early DSA) and compared mid-term
      outcomes in patients with or without DSA. METHODS: Between January 2009 and
      August 2013, 546 patients underwent lung transplantation at our institution. One
      hundred (18%) patients developed early DSA (Group A) and 446 (82%) patients
      (Group B) did not. Patient records were retrospectively reviewed. RESULTS:
      Retransplantation (odds ratio [OR] = 2.7, 95% confidence interval [CI] 1.1 to
      6.5, p = 0.03), pre-operative HLA antibodies (OR = 2.1, 95% CI 1.2 to 3.4, p =
      0.003) and primary graft dysfunction (PGD) score Grade 2 or 3 at 48 hours (OR =
      2.6, 95% CI 1.5 to 4.6, p = 0.001) were associated with early DSA development.
      Overall, 1- and 3-year survival in Group A and B patients was 79 +/- 4% vs 88 +/-
      2% and 57 +/- 8% vs 74 +/- 3%, respectively (p = 0.019). Eleven Group A (11%) and
      32 Group B (7%) patients died before hospital discharge (p = 0.34). Among
      patients surviving beyond discharge, 1- and 3-year survival in Group A and B
      patients was 89 +/- 4% vs 95 +/- 1% and 65 +/- 8% vs 80 +/- 3% in Group A and B
      patients, respectively (p = 0.04). Multivariate analysis identified early anti
      HLA Class II DSA (OR = 1.9, 95% CI 1.0 to 3.4, p = 0.04) as an independent risk
      factor for post-discharge mortality but not for in-hospital mortality.
      CONCLUSIONS: Pre-operative HLA antibodies, retransplantation or post-operative
      PGD increase the risk of developing early DSA, which were independently
      associated with an increased risk for mortality.

PMID- 25070909
TI  - WITHDRAWN: Pre-operative endometrial thinning agents before endometrial
      destruction for heavy menstrual bleeding.

PMID- 25070910
TI  - A fish is not a fish: patterns in fatty acid composition of aquatic food may have
      had implications for hominin evolution.
AB  - From c. 2 Ma (millions of years ago) onwards, hominin brain size and cognition
      increased in an unprecedented fashion. The exploitation of high-quality food
      resources, notably from aquatic ecosystems, may have been a facilitator or driver
      of this phenomenon. The aim of this study is to contribute to the ongoing debate
      on the possible role of aquatic resources in hominin evolution by providing a
      more detailed nutritional context. So far, the debate has focused on the relative
      importance of terrestrial versus aquatic resources while no distinction has been
      made between different types of aquatic resources. Here we show that Indian Ocean
      reef fish and eastern African lake fish yield on average similarly high amounts
      of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid
      (AA). Hence a shift from exploiting tropical marine to freshwater ecosystems (or
      vice versa) would entail no material difference in dietary long-chain
      polyunsaturated fatty acid (LC-PUFA) availability. However, a shift to marine
      ecosystems would likely mean a major increase in access to brain-selective
      micronutrients such as iodine. Fatty fish from marine temperate/cold waters yield
      twice as much DHA and four times as much EPA as tropical fish, demonstrating that
      a latitudinal shift in exploitation of African coastal ecosystems could
      constitute a significant difference in LC-PUFA availability with possible
      implications for brain development and functioning. We conclude that exploitation
      of aquatic food resources could have facilitated the initial moderate hominin
      brain increase as observed in fossils dated to c. 2 Ma, but not the exceptional
      brain increase in later stages of hominin evolution. We propose that the
      significant expansion in hominin brain size and cognition later on may have been
      aided by strong directional selecting forces such as runaway sexual selection of
      intelligence, and nutritionally supported by exploitation of high-quality food
      resources in stable and productive aquatic ecosystems.

PMID- 25070912
TI  - Endometrial pattern, thickness and growth in predicting pregnancy outcome
      following 3319 IVF cycle.
AB  - A retrospective study of 3319 women was conducted to assess predictive ability of
      endometrial characteristics for outcomes of IVF and embryo transfer. Endometrial
      thickness, growth and pattern were assessed at two time points (day 3 of
      gonadotrophin stimulation and day of HCG administration). Endometrial patterns
      were classified as pattern A: triple-line pattern comprising a central
      hyperechoic line surrounded by two hypoechoic layers; pattern B: an intermediate
      isoechogenic pattern with the same reflectivity as the surrounding myometrium and
      poorly defined central echogenic line; and pattern C: homogenous, hyperechogenic
      endometrium. The endometrium of pregnant women was thinner on day 3 of
      stimulation, thicker on the day of HCG administration, and showed greater growth
      in thickness compared with non-pregnant women. Clinical pregnancy rates differed
      according to endometrial pattern on the day of HCG administration (55.2%, 50.9%
      and 37.4% for patterns A, B and C, respectively). A positive linear relationship
      was found between endometrial thickness on the day of HCG administration and
      clinical pregnancy rate. Endometrial thickness, change and pattern were
      independent factors affecting outcome. Receiver operator characteristic curves
      showed that endometrial pattern, thickness and changes were not good predictors
      of clinical pregnancy. Discriminant analysis indicated that 58.7% of original
      grouped cases were correctly classified. Although endometrium with triple-line or
      increased thickness may favour pregnancy, combined endometrial characteristics do
      not predict outcomes. 

PMID- 25070913
TI  - Degradation of Fe/N/C catalysts upon high polarization in acid medium.
AB  - A comprehensive study of the degradation of a highly active Fe/N/C catalyst in
      acid medium is reported. An accelerated aging protocol was applied in the
      temperature range of 20 to 80  degrees C. From fundamental rotating-disc
      electrode studies and polymer electrolyte membrane fuel cell investigations
      combined with identical-location electron microscopy and Mobetabauer spectroscopy
      at various stages of degradation, important insights into the structural and
      chemical changes of the catalyst were obtained. Most importantly, the degradation
      is strongly enhanced at elevated temperature, which is correlated to (i)
      increased carbon-corrosion rate and (ii) parallel non-preferential dissolution of
      the FeNx-based active sites. The degradation not only leads to a decreased ORR
      kinetics over time but also induces significant charge- and mass-transport
      resistances due to the collapse of the electrode structure.

PMID- 25070914
TI  - Penile prostheses and the litigious patient: a legal database review.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common problem with significant
      impact on patient quality of life. Penile prosthesis implantation provides an
      effective treatment for ED but as an invasive procedure carries with it an
      increased risk of medicolegal liability. AIM: To investigate factors associated
      with malpractice litigation surrounding penile prosthesis implantation. METHODS:
      The Westlaw legal database was used to perform an advanced search for case
      reports using the term "medical malpractice" in combination with "penile" or
      "penis" and "prosthesis" or "implant" with dates between the January 1990 and
      December 2013. MAIN OUTCOME MEASURES: Each report was examined for trial
      information including patient demographics, device model and indications, alleged
      breach of duty, alleged damages, progression to trial, case outcome, and
      plaintiff award(s). RESULTS: The initial search yielded 76 cases that were
      narrowed to 40 after exclusions. There were 23 (57.5%) cases that were found in
      favor of the defendant, while 17 (42.5%) cases led to indemnity payment to the
      plaintiff including two cases (5.0%) that were settled out of court and 15
      (37.5%) favoring the plaintiff in front of a jury. The mean settlement received
      was $335,500 compared with the mean indemnity award of $831,050 for verdicts
      decided in favor of the plaintiff (P = 0.68). The most common breach of duty was
      error in surgical decision making, present in 20 cases (48.8%). Informed consent
      was an issue in 13 filings (31.7%), and postoperative infection was seen in 13
      cases (31.7%). In cases that identified the type of implant used, 58.3% were
      malleable implants, and 41.7% were inflatable devices. CONCLUSIONS: The main
      issues involved in malpractice litigation for penile prosthesis implants included
      surgical performance, informed consent, and postoperative management. Urologists
      must be aware of these potential issues in order to minimize their malpractice
      liability.

PMID- 25070915
TI  - Ephrin-A3 and ephrin-A4 contribute to microglia-induced angiogenesis in brain
      endothelial cells.
AB  - The association of microglia with brain vasculature during development and the
      reduced brain vascular complexity in microglia-deficient mice suggest the role of
      microglia in cerebrovascular angiogenesis. However, the underlying molecular
      mechanism remains unclear. Here, using an in vitro angiogenesis model, we found
      the culture supernatant of BV2 microglial cells significantly enhanced capillary
      like tube formation and migration of brain microvascular endothelial cells
      (BMECs). The expression of angiogenic factors, ephrin-A3 and ephrin-A4, were
      specifically upregulated in BMECs exposed to BV2-derived culture supernatant.
      Knockdown of ephrin-A3 and ephrin-A4 in BMECs by siRNA significantly attenuated
      the enhanced angiogenesis and migration of BMECs induced by BV2 supernatant. Our
      further results indicated that the ability of BV2 supernatant to promote
      endothelial angiogenesis was caused by the soluble tumor necrosis factor alpha
      (TNF-alpha) released from BV2 microglial cells. Moreover, the upregulations of
      ephrin-A3 and ephrin-A4 in BMECs in response to BV2 supernatant were effectively
      abolished by neutralization antibody against TNF-alpha and TNF receptor 1,
      respectively. The present study provides evidence that microglia upregulates
      endothelial ephrin-A3 and ephrin-A4 to facilitate in vitro angiogenesis of brain
      endothelial cells, which is mediated by microglia-released TNF-alpha.

PMID- 25070916
TI  - CORR Insights (r): Are copy number variants associated with adolescent idiopathic
      scoliosis?

PMID- 25070917
TI  - CORR Insights (r): Does fracture affect the healing time or frequency of
      recurrence in a simple bone cyst of the proximal femur?

PMID- 25070918
TI  - How have alternative bearings and modularity affected revision rates in total hip
      arthroplasty?
AB  - BACKGROUND: Total hip arthroplasty (THA) continues to be one of the most
      successful surgical procedures in the medical field. However, over the last two
      decades, the use of modularity and alternative bearings in THA has become
      routine. Given the known problems associated with hard-on-hard bearing couples,
      including taper failures with more modular stem designs, local and systemic
      effects from metal-on-metal bearings, and fractures with ceramic-on-ceramic
      bearings, it is not known whether in aggregate the survivorship of these implants
      is better or worse than the metal-on-polyethylene bearings that they sought to
      replace. QUESTIONS/PURPOSES: Have alternative bearings (metal-on-metal and
      ceramic-on-ceramic) and implant modularity decreased revision rates of primary
      THAs? METHODS: In this systematic review of MEDLINE and EMBASE, we used several
      Boolean search strings for each topic and surveyed national registry data from
      English-speaking countries. Clinical research (Level IV or higher) with >= 5
      years of followup was included; retrieval studies and case reports were excluded.
      We included registry data at >= 7 years followup. A total of 32 studies (and five
      registry reports) on metal-on-metal, 19 studies (and five registry reports) on
      ceramic-on-ceramic, and 20 studies (and one registry report) on modular stem
      designs met inclusion criteria and were evaluated in detail. Insufficient data
      were available on metal-on-ceramic and ceramic-on-metal implants, and monoblock
      acetabular designs were evaluated in another recent systematic review so these
      were not evaluated here. RESULTS: There was no evidence in the literature that
      alternative bearings (either metal-on-metal or ceramic-on-ceramic) in THA have
      decreased revision rates. Registry data, however, showed that large head metal-on
      metal implants have lower 7- to 10-year survivorship than do standard bearings.
      In THA, modular exchangeable femoral neck implants had a lower 10-year survival
      rate in both literature reviews and in registry data compared with combined
      registry primary THA implant survivorship. CONCLUSIONS: Despite improvements in
      implant technology, there is no evidence that alternative bearings or modularity
      have resulted in decreased THA revision rates after 5 years. In fact, both large
      head metal-on-metal THA and added modularity may well lower survivorship and
      should only be used in select cases in which the mission cannot be achieved
      without it. Based on this experience, followup and/or postmarket surveillance
      studies should have a duration of at least 5 years before introducing new
      alternative bearings or modularity on a widespread scale.

PMID- 25070919
TI  - High tibial valgus osteotomy: closing, opening or combined? Patellar height as a
      determining factor.
AB  - BACKGROUND: According to the literature, closing and opening wedge high tibial
      valgus osteotomies can raise or lower the patella, and different methods of
      patella height measurement show similarly conflicting results. Clarification of
      this was thought to be important because there is much literature describing
      morbidity secondary to patella alta or patella infera (baja). Effects on tibial
      slope and patellar tendon length are not well delineated and the influence of sex
      and age is unknown. QUESTIONS/PURPOSE: A group of patients who underwent high
      tibial valgus osteotomy was investigated to determine how surgical technique
      influenced postoperative (1) patellar height and (2) tibial slope and patellar
      tendon length, and (3) whether age or gender independently influenced
      postoperative patellar height. To eliminate the often conflicting results seen
      when several ratio methods are used, patellar height was measured by one method,
      before and after surgery, shown previously to be reliable. METHODS: Patellar
      height was measured on radiographs using the plateau-patella angle in a
      retrospective case series consisting of three cohorts: 18 patients with closing
      wedge osteotomies, 26 with opening wedge osteotomies, and 32 with combined
      osteotomies. The indication for surgery in all three cohorts was medial
      osteoarthritis with secondary varus. Before surgery there were no significant
      differences in patellar height, femorotibial angle, age, or gender among the
      three groups, and no patients were lost to followup during the 8-week study
      period after surgery. Seven of the 76 patients (9.2%), all in the opening wedge
      cohort, had concomitant ACL reconstruction at the time of the tibial osteotomy.
      No other surgery, except arthroscopy, was performed at the time of osteotomy.
      Patellar tendon length was assessed by the Insall-Salvati index and tibial slope
      by the angle between the posterior tibial cortex and the medial tibial joint
      line. Postoperative measurements were made between 6 and 8 weeks. The influence
      of sex and age was calculated using patellar height measurements made before any
      surgery. RESULTS: All closing wedge osteotomies produced patellar ascent by an
      average of 13% (p<0.001), all opening wedges produced descent by an average of
      21% (p<0.001), and the combined osteotomy mean showed minimal change (p=0.0034).
      The absolute consistency of the changes and their direction allow suggested
      guidelines for selection of osteotomy type. There were only slight changes in
      tibial slope. A significant change in patellar tendon length was seen in seven
      knees of the opening wedge cohort that had concomitant ACL reconstruction. All
      had a mean reduction of the Insall-Salvati index of 0.05 (approximately 5%),
      p=0.0002. New findings showed higher patellae in female and older patients,
      unrelated to the surgery. CONCLUSIONS: If it is accepted that patella baja and
      patella alta should be avoided, then closing wedge osteotomies should be
      performed only when the patella is low riding, and opening wedge osteotomies
      should be done only for patients with preexisting patella alta. The combined
      osteotomy minimizes changes in patellar height. Patellar tendon contractures and
      tibial slope changes can be avoided. The plateau-patella angle should be measured
      preoperatively to help decide the type of osteotomy. LEVEL OF EVIDENCE: Level
      III, therapeutic study. See the Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25070921
TI  - Breast milk bar code scanning results in time savings and staff efficiency.

PMID- 25070920
TI  - Is synovial C-reactive protein a useful marker for periprosthetic joint
      infection?
AB  - BACKGROUND: Serum C-reactive protein (CRP) is a general marker of inflammation,
      and recent studies suggest that measurement of CRP in synovial fluid may be a
      more accurate method for diagnosing periprosthetic joint infection (PJI).
      QUESTIONS/PURPOSES: We aimed to (1) determine if there is a correlation between
      serum and synovial CRP values, (2) establish cutoff values for diagnosing
      infection based on serum and synovial CRP, and (3) compare the utility of
      measuring CRP in synovial fluid versus serum for the diagnosis of PJI using
      standard assay equipment available at most hospitals. METHODS: Between February
      2011 and March 2012, we invited all 150 patients scheduled for revision TKA (84)
      or THA (66) to participate in this prospective study, of whom 100% agreed. Data
      ultimately were missing for 31 patients, leaving 60 patients undergoing revision
      TKA and 59 undergoing revision THA (71% and 89% of the original group,
      respectively) for whom CRP level was measured in serum and synovial fluid
      samples. Patients were deemed to have a PJI (32) or no infection (87) using
      Musculoskeletal Infection Society criteria. Serum and synovial CRP levels were
      assayed using the same immunospectrophotometer and the correlation coefficient
      was calculated. Receiver operating characteristic curve analyses were performed
      to compare utility in diagnosing PJI, which included area under the curve,
      diagnostic threshold, and test sensitivity, specificity, predictive values, and
      accuracy. In 22 of 150 patients (14.7%), synovial CRP could not be measured
      because the sample was too viscous or hemolyzed. RESULTS: In the analyzed 119
      samples, there was a strong correlation (r = 0.76; p < 0.001) between synovial
      and serum CRP. The area under the curve was 0.90 both for the synovial fluid (95%
      CI, 0.82-0.97) and serum (95% CI, 0.84-0.96) CRP assays. The diagnostic
      thresholds were 6.6 mg/L for synovial fluid and 11.2 mg/L for serum.
      Sensitivities, specificities, positive predictive value, negative predictive
      value, and accuracies were similar for synovial fluid and serum assays.
      CONCLUSIONS: Although recent studies have suggested a superiority of synovial
      fluid CRP over serum CRP for the diagnosis of PJI, we found that measurement of
      CRP in synovial fluid rather than serum using readily available assay equipment
      does not offer a diagnostic advantage in detection of PJIs. LEVEL OF EVIDENCE:
      Level II, diagnostic study. See the Instructions to Authors for a complete
      description of levels of evidence.

PMID- 25070922
TI  - What types of terms do people use when describing an individual's personality?
AB  - An important yet untested assumption within personality psychology is that more
      important person characteristics are more densely reflected in language. We
      investigated how ratings of importance and other term properties are associated
      with one another and with a term's frequency of use. Research participants were
      asked to provide terms that described individuals they knew, which resulted in a
      set of 624 adjectives. These terms were independently rated for importance,
      social desirability, observability, stateness versus traitness, level of
      abstraction, and base rate. Terms rated as describing more important person
      characteristics were in fact used more often by the participants in the sample
      and in a large corpus of online communications (close to 500 million words). More
      frequently used terms and more positive terms were also rated as being more
      abstract, more traitlike, and more widely applicable (i.e., having a greater base
      rate). We discuss the implications of these findings with regard to person
      perception in general. 

PMID- 25070923
TI  - Precise characterization method of antibody-conjugated magnetic nanoparticles for
      pathogen detection using stuffer-free multiplex ligation-dependent probe
      amplification.
AB  - Antibody-conjugated magnetic nanoparticles (Ab-MNPs) have potential in pathogen
      detection because they allow target cells to be easily separated from complex
      sample matrices. However, the sensitivity and specificity of pathogen capture by
      Ab-MNPs generally vary according to the types of MNPs, antibodies, and sample
      matrices, as well as preparation methods, including immobilization. Therefore,
      achieving a reproducible analysis utilizing Ab-MNPs as a pathogen detection
      method requires accurate characterization of Ab-MNP capture ability and
      standardization of all handling processes. In this study, we used high-resolution
      CE-single strand conformational polymorphism coupled with a stuffer-free
      multiplex ligation-dependent probe amplification system to characterize Ab-MNPs.
      The capture ability of Ab-MNPs targeting Salmonella enteritidis and nine
      pathogens, including S. enteritidis, was analyzed in phosphate buffer and milk.
      The effect of storage conditions on the stability of Ab-MNPs was also assessed.
      The results showed that the stuffer-free multiplex ligation-dependent probe
      amplification system has the potential to serve as a standard characterization
      method for Ab-MNPs. Moreover, the precise characterization of Ab-MNPs facilitated
      robust pathogen detection in various applications. 

PMID- 25070924
TI  - Highly sensitive and selective fluorometric/electrochemical dual-channel sensors
      for TNT and DNT explosives.
AB  - A novel electro-active compound, TCAC, is synthesized and its electrochemical
      polymerized film is used to detect 2,4,6-trinitrotoluene (TNT) and 2,4
      dinitrotoluene (DNT) explosives through a fluorometric/electrochemical dual
      channel sensor with high sensitivity and selectivity. In particular, the
      electrochemical sensor for the analysis of TNT had an enhanced sensitivity of 0.5
      MUM. The detection limit of the sensor was calculated to be 15 nM. 

PMID- 25070925
TI  - Influence of ketamine-xylazine anaesthesia on cubic and quadratic high-frequency
      distortion-product otoacoustic emissions.
AB  - Ketamine is a dissociative anaesthetic, analgesic drug as well as an N-methyl-D
      aspartate receptor antagonist and has been reported to influence otoacoustic
      emission amplitudes. In the present study, we assess the effect of ketamine
      xylazine on high-frequency distortion-product otoacoustic emissions (DPOAE) in
      the bat species Carollia perspicillata, which serves as model for sensitive high
      frequency hearing. Cubic DPOAE provide information about the nonlinear gain of
      the cochlear amplifier, whereas quadratic DPOAE are used to assess the symmetry
      of cochlear amplification and potential efferent influence on the operating state
      of the cochlear amplifier. During anaesthesia, maximum cubic DPOAE levels can
      increase by up to 35 dB within a medium stimulus level range from 35 to 60 dB
      SPL. Close to the -10 dB SPL threshold, at stimulus levels below about 20-30 dB
      SPL, anaesthesia reduces cubic DPOAE amplitudes and raises cubic DPOAE
      thresholds. This makes DPOAE growth functions steeper. Additionally, ketamine
      increases the optimum stimulus frequency ratio which is indicative of a reduction
      of cochlear tuning sharpness. The effect of ketamine on cubic DPOAE thresholds
      becomes stronger at higher stimulus frequencies and is highly significant for f2
      frequencies above 40 kHz. Quadratic DPOAE levels are increased by up to 25 dB by
      ketamine at medium stimulus levels. In contrast to cubic DPOAEs, quadratic DPOAE
      threshold changes are variable and there is no significant loss of sensitivity
      during anaesthesia. We discuss that ketamine effects could be caused by
      modulation of middle ear function or a release from ipsilateral efferent
      modulation that mainly affects the gain of cochlear amplification.

PMID- 25070926
TI  - THC may reproducibly induce electrical hyperalgesia in healthy volunteers.

PMID- 25070927
TI  - Group trauma-informed treatment for adolescent psychiatric inpatients: a
      preliminary uncontrolled trial.
AB  - Despite high rates of trauma exposure (46%-96%) and significant posttraumatic
      stress disorder (PTSD; 21%-29%) symptoms in adolescent psychiatric inpatients,
      there is a dearth of research on effective interventions delivered in inpatient
      settings. The current report describes the development of Brief STAIR-A, a
      repeatable 3-module version of skills training in affective and interpersonal
      regulation (STAIR) developed for adolescents in inpatient care. An uncontrolled
      design was used to conduct a preliminary examination of the group intervention's
      effectiveness. Adolescent psychiatric inpatients (N = 38; ages 12 years-17 years)
      admitted to a public hospital participated in Brief STAIR-A and attended a median
      of 6 sessions (range 3-36). They completed measures of PTSD and depressive
      symptom severity, coping skill use, and coping efficacy upon admission and again
      prior to discharge. Participants reported significant reductions in symptom
      severity (d = 0.65-0.67), no change in the absolute level of coping skills used
      (d = 0.16), but greater coping efficacy when discharged from care (d = 0.75).
      Results from this pilot study suggest that this brief group treatment shows
      promise for treating adolescents' trauma-related difficulties in inpatient
      psychiatry settings, but additional research examining its effectiveness is
      essential. 

PMID- 25070928
TI  - Inhibitory control dysfunction in nicotine dependence and the influence of short
      term abstinence.
AB  - BACKGROUND: Although the majority of substance use disorders depict reliable
      deficits in inhibitory control (IC), similar deficits are not consistently found
      in nicotine dependence. The mixed results of past research may have been due to
      confounding variables known to independently influence IC function, including
      age, concurrent drug use and particularly, length of nicotine abstinence.
      METHODS: A stop signal task was used to examine stop signal reaction time (SSRT),
      a typical measure of IC, in nicotine dependence across two studies that attempted
      to closely control for IC confounds. Study 1 compared the SSRT of 37 dependent
      cigarette smokers (11 females) to 36 non-smokers (13 females), following 3-h of
      nicotine abstinence. Study 2 compared 22 dependent cigarette smokers' (11
      females) SSRT scores when satiated on nicotine to their performance following 10
      h of nicotine abstinence. RESULTS: Nicotine dependent individuals did not differ
      from controls in SSRT performance following 3-h abstinence, but showed a
      significant decline in performance following 10-h abstinence, when compared to
      nicotine satiation. CONCLUSIONS: During shorter abstinence periods, the acute
      benefits of nicotine satiation appear to facilitate inhibitory control; however,
      IC was poorer during extended periods of nicotine abstinence. In turn, this
      suggests that the reliability of IC dysfunction in nicotine dependence varies
      according to abstinence length and needs to be carefully considered for future
      behavioural and neuroimaging examination of IC within this population.

PMID- 25070929
TI  - Evaluation of skin viability effect on ethosome and liposome-mediated psoralen
      delivery via cell uptake.
AB  - This study investigated the effect of skin viability on its permeability to
      psoralen delivered by ethosomes, as compared with liposomes. With decreasing skin
      viability, the amount of liposome-delivered psoralen that penetrated through the
      skin increased, whereas skin deposition of psoralen from both ethosomes and
      liposomes reduced. Psoralen delivery to human-immortalized epidermal cells was
      more effective using liposomes, whereas delivery to human embryonic skin
      fibroblast cells was more effective when ethosomes were used. These findings
      agreed with those of in vivo studies showing that skin psoralen deposition from
      ethosomes and liposomes first increased and then plateaued overtime, which may
      indicate gradual saturation of intracellular drug delivery. It also suggested
      that the reduced deposition of ethosome- or liposome-delivered psoralen in skin
      with reduced viability may relate to reduced cellular uptake. This work indicated
      that the effects of skin viability should be taken into account when evaluating
      nanocarrier-mediated drug skin permeation.

PMID- 25070931
TI  - Multielectrode Pulmonary Vein Ablation Catheter (PVAC((r))): current data on
      results and risks.
AB  - Electrical isolation of pulmonary veins is the cornerstone of catheter ablation
      for patients with symptomatic atrial fibrillation. However, uncertainty surrounds
      the choice of energy source in pulmonary vein isolation (PVI). Various
      alternative techniques such as the Pulmonary Vein Ablation Catheter (PVAC((r)),
      Medtronic Inc., Minneapolis, MN, USA) have been developed to facilitate PVI. This
      over-the-wire multielectrode catheter is delivering duty-cycled bipolar and
      unipolar radiofrequency (RF) energy at relatively low power.PVI with this "one
      shot" PVACatheter can shorten the procedure duration and lower fluoroscopy time
      compared to irrigated RF. It enables mapping and ablation with the same array,
      but fails to show signals during RF energy delivery. The effectiveness of PVAC is
      comparable to other technologies in randomized studies. The overall complication
      rate of PVAC PVI is comparable to irrigated RF and possibly slightly higher for
      cryoballoon PVI. Special attention has to be paid to an effective anticoagulation
      throughout the ablation procedure, avoidance of embolic events and pulmonary
      venous stenosis.The novel catheter design of the PVAC Gold((r)) array may improve
      safety by reducing embolic events through avoidance of electrode 1-to-10
      interaction and by better tissue contact due to the 20 degrees  forward tilt.
      Although clinical data with this new array are lacking so far, the PVAC system
      has been shown to be a promising tool for PVI. However, prospective studies
      especially with the novel array are required to determine its true role for
      catheter ablation of atrial fibrillation in the future. 

PMID- 25070930
TI  - Sleep-disordered breathing and inappropriate defibrillator shocks in chronic
      heart failure.
AB  - PURPOSE: Supraventricular tachyarrhythmias are a major cause of inappropriate
      defibrillator shocks. Sleep-disordered breathing (SDB) is a known risk factor for
      atrial fibrillation (AF). We hypothesized that Cheyne-Stokes respiration (CSA)
      and obstructive sleep apnea (OSA) have an impact on inappropriate defibrillator
      discharges in patients witch chronic heart failure (CHF) and cardiac
      resynchronization therapy with defibrillator (CRT-D). METHODS: In this study, 172
      patients with CHF (LVEF <= 45 %, NYHA-class >= 2) and CRT-D underwent overnight
      polygraphy; 54 had no SDB (apnea-hypopnea index < 5/h), 59 had OSA, and 59 had
      CSA. During follow-up (36 months), inappropriate defibrillator shocks were
      documented. RESULTS: In all, 17 patients had inappropriate defibrillator shocks
      (9.9 %; eight oversensing due to lead fractures, five caused by atrial
      fibrillation, four because of sinus tachycardia). Mean event-free survival time
      was 33.5 +/- 1.2 months in the CSA group, 35.2 +/- 0.7 months in the OSA group,
      and 32.1 +/- 1.5 months in the no SDB group, respectively (CSA vs. no SDB p =
      0.63; OSA vs. no SDB p = 0.31; CSA vs. OSA p = 0.45). Stepwise Cox proportional
      hazard regression analysis revealed an independent association for age (per year:
      hazard ratio 0.90, 95 % confidence interval 0.85-0.96, p < 0.001), but not for
      any kind of SDB. CONCLUSIONS: SDB was not associated with inappropriate
      defibrillator shocks. We assume this is due to the low incidenceand low
      proportion of inappropriate therapies in response to AF.

PMID- 25070932
TI  - [Catheter ablation of paroxysmal atrial fibrillation: state of the art].
AB  - Atrial fibrillation is the most common form of arrhythmia worldwide and is
      associated with potentially severe complications. Apart from antiarrhythmic drug
      therapy, interventional treatment by catheter ablation has emerged as an
      effective and safe alternative notably for the paroxysmal form. The pulmonary
      veins (PV) have been identified as a major source in the setting of paroxysmal
      atrial fibrillation. Circumferential wide area PV isolation, optimization of
      procedural techniques and the positioning of an ablation line deep in the left
      atrium have contributed to the increased success rates; however, the procedure is
      still associated with potentially severe complications and should therefore be
      carried out in centers with sufficient case numbers and operators with
      corresponding training and experience. 

PMID- 25070933
TI  - [Interventional treatment of tachyarrhythmia in children with congenital heart
      disease].
AB  - In children and adolescents with congenital heart disease (CHD) tachyarrhythmia
      occurs more frequently compared to patients with otherwise normal hearts.
      Arrhythmia substrates may be a natural part of certain congenital cardiac
      malformations or may result from long lasting myocardial deterioration as a
      result of CHD and/or cardiac surgery. Treatment of tachycardia is more frequently
      required even in early childhood, as the impact on quality of life, morbidity and
      mortality is higher due to an often reduced hemodynamic tolerance. Over the past
      20 years interventional electrophysiology has been established as the therapy of
      choice for the majority of chronic or chronically recurrent tachycardia even in
      children with CHD. The success and risks of treatment are predominantly
      influenced by the individual expression of the cardiac anomaly and, if surgery
      has been performed, the highly variant postoperative anatomy. Introduction of 3D
      electroanatomical mapping systems together with modern cardiac imaging tools have
      significantly contributed to an improved understanding, particularly in
      postoperative tachycardia. Despite such progress, success rates are lower and
      recurrences are more frequent compared to patients without CHD. Complex and often
      multiple tachycardia courses account for the still limited performance as well as
      a frequently insufficient lesion formation with the use of radiofrequency current
      in the hypertrophic and fibrotic myocardium. Electrophysiology in children and
      adolescents, particularly if CHD is present, represents a highly specialized
      discipline requiring a high expertise in CHD, CHD surgery and cardiac
      electrophysiology and is ideally imbedded within an interdisciplinary
      cardiological and cardiosurgical setting. 

PMID- 25070934
TI  - Device therapy in children with and without congenital heart disease.
AB  - Device therapy in children has undergone several changes over the last few years
      due to developments in technology as well new approaches to preservation of
      ventricular function in paediatric pacing, novel data on pacing lead survival,
      inclusion of cardiac resynchronisation therapy and accumulating experience with
      the implantable cardioverter-defibrillator. Despite these developments device
      therapy in children is still associated with significant complications mainly due
      to patient size, growth and underlying structural heart disease. The amount of
      available data on therapy outcomes is much smaller than in their adult
      counterparts and prospective randomized studies are completely missing. Thus
      device therapy has to be cautiously tailored to individual patient needs having
      in mind the specific situation of expected decades of treatment. Avoidance of
      complications and potential harm precluding successful therapy continuation in
      the future should be one of the main principles.

PMID- 25070935
TI  - Local structure and lithium mobility in intercalated Li3Al(x)Ti(2-x)(PO4)3
      NASICON type materials: a combined neutron diffraction and NMR study.
AB  - The structural features of intercalated Li3AlxTi2-x(PO4)3 compounds, with x = 0
      and 0.2, have been deduced by Rietveld analysis of neutron diffraction (ND)
      patterns recorded between 100 and 500 K. The Li insertion decreases the symmetry
      from R3c to R3 in analyzed compounds. In pristine Li1+xAlxTi2-x(PO4)3 samples, Li
      occupies mainly six-fold M1 sites at ternary axes; but in lithiated Li3AlxTi2
      x(PO4)3 samples, Li is located near M2 positions at M3/M3' four-fold coordinated
      sites. In both cases, Li arrangement minimizes electrostatic Li-Li repulsions.
      The insertion of lithium resulted in the reduction of Ti(4+) to Ti(3+) that
      shifts (7)Li, (27)Al and (31)P MAS-NMR resonances towards more positive chemical
      shifts, improving the resolution of different sites. The detection of twelve
      components in (7)Li MAS-NMR spectra recorded at room temperature suggests the
      location of Li(+) ions at three-oxygen faces that define M2 cavities. From (7)Li
      MAS-NMR spectra, the occupancy of sites and mobility of lithium were investigated
      in the temperature range 100-500 K. The correlation between structural
      information, deduced by neutron diffraction, and lithium mobility, deduced by NMR
      spectroscopy, provides new insights into structural factors that affect lithium
      mobility in materials with NASICON structure.

PMID- 25070936
TI  - Objective versus subjective outcome measures of biofeedback: what really matters?
AB  - OBJECTIVE: Clinical epidemiologic studies suggest that once established, voiding
      dysfunction can become a lifelong condition if not treated correctly early on in
      life. Biofeedback is one component of a voiding retraining program to help
      children with voiding dysfunction. Our goal was to compare objective non-invasive
      urodynamic data obtained during office biofeedback sessions with patient reported
      voiding symptom scores. METHODS: Charts of 55 children referred in 2010 for
      pelvic floor muscle biofeedback therapy for urinary incontinence were
      retrospectively reviewed. Patients with any anatomic diagnoses were excluded.
      Forty-seven (86%) females and eight males (14%) with a mean age of 8.2 years made
      up the cohort. Uroflow curves, voided volumes, and post-void residuals were
      recorded at each visit and served as objective data. Volumes were normalized as a
      percentage of expected bladder capacity according to age. The patient reported
      symptom score and patient reported outcome (improved, no change or worse) served
      as subjective measures of intervention. RESULTS: The primary referral diagnoses
      were day and night wetting in 37 (67%) and daytime incontinence in 18 (33%)
      children. A history of urinary tract infection (UTI) was noted in 32 (64%)
      patients, and 25% were maintained on antibiotic prophylaxis during the study
      period. Twenty-nine percent were maintained on anticholinergic medication.
      Patients attended an average of 2.5 biofeedback sessions. Voided volumes and post
      void residual volumes were unchanged, 50% of the abnormal uroflow curves
      normalized over the course of treatment (p < 0.05). Patient reported symptom
      score decreased from 12.8 +/- 5.6 to 8.0 +/- 6.5 (p < 0.002) over an average
      follow-up time of 276 days reflecting fewer daytime voiding symptoms. There was
      no significant change in the patient symptom score component for the night-time
      wetting. Patient-reported outcomes at the final session of biofeedback were rated
      an improved in 26 (47%), no change in 15 (27%), worse in three (5%) patients, and
      not rated in 11 patients (21%). CONCLUSIONS: Pelvic floor muscle biofeedback is
      associated with patient-reported improvement in symptoms, reduction in voiding
      symptom score, and normalization of uroflow curves, but these improvements are
      not correlated with objective parameters of voided volumes and post-void residual
      urine obtained during office visits for biofeedback. It is important to identify
      the most relevant outcome measures for BFB, as insurance coverage for medical
      interventions that cannot offer outcomes analysis that demonstrates a benefit for
      the patient will eventually be eliminated.

PMID- 25070938
TI  - Alcoholic liver disease in the intensive care unit: outcomes and predictors of
      prognosis.
AB  - BACKGROUND: An increasing number of patients with alcoholic liver disease (ALD)
      are being referred for critical care support, but limited information is
      available on their short- and medium-term outcomes. This study aimed to determine
      mortality rates, identify optimal predictors of prognosis, and determine the
      appropriate time to apply these predictors in patients with ALD admitted to
      intensive care unit (ICU). METHODS: In this retrospective study, patients
      admitted to ICU between 2009 and 2012 with a primary diagnosis of ALD were
      included. Survival was calculated using the Kaplan-Meier method, risk factors for
      death determined by logistic regression analysis, and discriminative capacity of
      models using receiver operating characteristic curves. RESULTS: Of 170 patients
      admitted with liver disease, 62 met the inclusion criteria. Survival rates in the
      ICU, in hospital, and at 6 months were 40.3% (95% confidence interval [CI], 30.7%
      49.9%), 35.5% (95% CI, 25.35%-45.65%), and 29% (95% CI, 19.4%-38.6%),
      respectively. Multiple linear regression analysis of day 1 variables produced an
      equation with Sequential Organ Failure Assessment score and lactate as
      significant predictors of mortality; this model had an area under the receiver
      operating characteristic curve of 0.93. A score greater than 12 in this model
      correlated with a mortality of more than 80% at all time points and was more
      accurate than any other score examined. CONCLUSION: Patients admitted to ICU with
      ALD have a very high inhospital mortality. A combination of the established
      Sequential Organ Failure Assessment score and lactate provided the most accurate
      predictor of outcome on day of admission and at all subsequent time points.

PMID- 25070937
TI  - Estimation of pro-renin as a prognostic marker for renal function in PUV
      patients.
AB  - OBJECTIVE: To estimate serum pro-renin, and its clinical significance, as a
      marker of chronic renal disease in posterior urethral valve (PUV) patients.
      PATIENTS AND METHODS: Forty patients with a PUV that were admitted to the
      hospital between 2010 and 2012 were reviewed. Twenty age-matched patients who
      were admitted for other non-urological diseases were selected for control.
      Clinical parameters, serum creatinine, urea, eGFR (estimated glomerular
      filtration rate) and serum pro-renin were analysed before and after valve
      ablation. RESULTS: Forty patients with PUV were included in the study. Three
      groups were formed according to age: <1 year, 1-3 years, >3 years. Pro-renin was
      measured using an ELISA (enzyme linked immunosorbent assay) kit and 'Graph Pad
      Prism' Software. The Spearman's rho test was used for correlation. Serum pro
      renin had a negative correlation with the age group (correlation coefficient 
      0.395, P-value 0.012), eGFR (correlation coefficient -0.850, P-value<0.001) and
      follow-up eGFR (correlation coefficient -0.471, P-value 0.002). The pro-renin
      level correlated positively with serum creatinine at presentation (correlation
      coefficient 0.671, P-value<0.001), blood urea at initial presentation
      (correlation coefficient 0.684, P-value<0.001), serum creatinine at follow-up
      (correlation coefficient 0.546, P-value<0.001) and blood urea at follow-up
      (correlation 0.603, P-value<0.001). CONCLUSION: Pro-renin measured before PUV
      repair is associated with renal function three months after surgery.

PMID- 25070939
TI  - Three phenotypes of anti-N-methyl-D-aspartate receptor antibody encephalitis in
      children: prevalence of symptoms and prognosis.
AB  - BACKGROUND: Anti-N-methyl-d-aspartate (NMDA) receptor antibody encephalitis is
      becoming an increasingly recognized cause of encephalopathy in individuals
      previously presumed to have viral encephalitis. Various manifestations of this
      disease include altered mental status, behavioral changes, seizures, and movement
      disorders. We have noted three distinct subtypes of this disease which appear to
      have differential responses to immunotherapies and differences in prognosis.
      METHODS AND PATIENTS: We report eight patients observed at our children's
      hospital from 2009 through 2013 who appear to clearly fall into one of our three
      clinical categories. To find comparable articles reflecting this classification,
      we then performed a MEDLINE search of all articles involving the subject heading
      "anti-NMDA receptor encephalitis" or just the keyword phrase "NMDA encephalitis,"
      and we found 162 articles to review. Twenty-two articles were eliminated due to
      basic science, and we were able to review 105 of the remaining articles, most of
      which were case reports or case series, although a few were larger reviews. For
      the sake of our review, we defined type 1 or "classic" anti-NMDA receptor
      antibody encephalitis as having a duration of <60 days and being characterized
      predominantly by a catatonic or stuporous state, type 2 or psychiatric
      predominant anti-NMDA receptor antibody encephalitis as having no noteworthy
      catatonic or stuporous state in addition to the presence of predominantly
      behavioral and psychiatric symptoms, and type 3 or catatonia-predominant anti
      NMDA receptor antibody encephalitis as having a duration of >=60 days in a
      predominantly catatonic or stuporous state. RESULTS: We note that the poorest
      responders, even to aggressive immunotherapies, are the patients with catatonia
      persistent type anti-NMDA receptor antibody encephalitis, which has, as its
      hallmark, prolonged periods of severe encephalopathy. Patients with predominantly
      psychiatric symptoms, which we call the psychiatric-predominant anti-NMDA
      receptor antibody encephalitis, have had excellent responses to plasma exchange
      or other immunotherapies and appear to have the least residual deficits at follow
      up. Patients with fairly equal representations of periods of altered mental
      status, behavioral problems, and movement disorders appear to have an
      intermediate prognosis and likely require early aggressive immunotherapy.
      CONCLUSIONS: In our series, we discuss representative examples of these clinical
      subtypes and their associated outcomes, and we suggest that tracking these
      subtypes in future cases of anti-NMDA receptor antibody encephalitis might lead
      to better understanding and better risk stratification with regard to
      immunotherapy decisions.

PMID- 25070940
TI  - Neglected tropical diseases, bioinformatics, and vaccines.

PMID- 25070941
TI  - Advanced immune suppression is associated with increased prevalence of mixed
      strain Mycobacterium tuberculosis infections among persons at high risk for drug
      resistant tuberculosis in Botswana.
AB  - We examined factors associated with mixed-strain Mycobacterium tuberculosis
      infections among patients at high risk for drug-resistant tuberculosis in
      Botswana. Thirty-seven (10.0%) of 370 patients with tuberculosis had mixed M.
      tuberculosis infections, based on 24-locus mycobacterial interspersed repetitive
      unit-variable number of tandem repeats genotyping. In log-binomial regression
      analysis, age <37 years (adjusted prevalence ratio [PR], 1.92; 95% confidence
      interval [CI], 1.01-3.57) and prior tuberculosis treatment (adjusted PR, 2.31;
      95% CI, 1.09-4.89) were associated with mixed M. tuberculosis infections. Among
      human immunodeficiency virus-infected patients, prior tuberculosis treatment
      (adjusted PR, 2.11; 95% CI, 1.04-4.31) and CD4(+) T-cell count of <100 cells/MUl
      (adjusted PR, 10.18; 95% CI, 2.48-41.71) were associated with mixed M.
      tuberculosis infections. Clinical suspicion of mixed M. tuberculosis infections
      should be high for patients with advanced immunosuppression and a prior history
      of tuberculosis treatment. 

PMID- 25070942
TI  - Can mass drug administration lead to the sustainable control of schistosomiasis?
AB  - BACKGROUND: In the Philippines, the current national control strategy for
      schistosomiasis is annual mass drug administration (MDA) with 40 mg/kg of
      praziquantel in all schistosomiasis-endemic villages with a prevalence >=10%.
      METHODS: A cross-sectional survey of schistosomiasis was conducted in 2012 on 18
      221 individuals residing in 22 schistosomiasis-endemic villages in the province
      of Northern Samar. The prevalence of schistosomiasis, intensity of Schistosoma
      infection, and morbidity of disease were assessed. RESULTS: Despite an active
      schistosomiasis-control program in Northern Samar for >30 years, which included a
      MDA campaign in the last 5 years, the mean prevalence of schistosomiasis among 10
      435 evaluated subjects was 27.1% (95% confidence interval [CI], 26.3%-28.0%), and
      the geometric mean intensity of infection among 2832 evaluated subjects was 17.2
      eggs per gram of feces (95% CI, 16.4-18.1). Ultrasonography revealed high levels
      of schistosomiasis-induced morbidity in the schistosomiasis-endemic communities.
      Left lobe liver enlargement (>=70 mm) was evident in 89.3% of subjects. Twenty
      five percent of the study population had grade II/III liver parenchyma fibrosis,
      and 13.3% had splenomegaly (>=100 mm). CONCLUSIONS: MDA on its own was
      insufficient to control the prevalence of schistosomiasis, intensity of
      Schistosoma infection, or morbidity of the disease. Alternative control measures
      will be needed to complement the existing national MDA program.

PMID- 25070943
TI  - From genome screening to creation of vaccine against Trypanosoma cruzi by use of
      immunoinformatics.
AB  - Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and
      activation of CD8(+) T cells is crucial for a protective immune response.
      Therefore, the identification of antigens with major histocompatibility complex
      class I epitopes is a crucial step for vaccine development against T. cruzi. Our
      aim was to identify novel antigens and epitopes by immunoinformatics analysis of
      the parasite proteome (12 969 proteins) and to validate their immunotherapeutic
      potential in infected mice. We identified 172 predicted epitopes, using NetMHC
      and RANKPEP. The corresponding protein sequences were reanalyzed to generate a
      consensus prediction, and 26 epitopes were selected for in vivo validation. The
      interferon gamma (IFN-gamma) recall response of splenocytes from T. cruzi
      infected mice confirmed that 10 of 26 epitopes (38%) induced IFN-gamma
      production. The immunotherapeutic potential of a mixture of all 10 peptides was
      evaluated in infected mice. The therapeutic vaccine was able to control T. cruzi
      infection, as evidenced by reduced parasitemia, cardiac tissue inflammation, and
      parasite burden and increased survival. These findings illustrate the benefits of
      this approach for the rapid development of a vaccine against pathogens with large
      genomes. The identified peptides and the proteins from which they are derived are
      excellent candidates for the development of a vaccine against T. cruzi. 

PMID- 25070944
TI  - Clinical Assessment of Fluid Balance is Incomplete for Colorectal Surgical
      Patients.
AB  - BACKGROUND AND AIMS: Fluid balance for the surgical patient has been proven very
      important for the postoperative outcome and development of complications. The aim
      of this study was to evaluate, for the first time in modern times, the accordance
      between nurse-based fluid charting (cumulated fluid balance) and body weight
      change for general surgical patients. MATERIAL AND METHODS: This was a
      descriptive study with prospectively collected data from two clinical randomized
      multicenter trials. A total of 113 patients from American Society of
      Anesthesiology group I-III undergoing elective colorectal surgery were included.
      Cumulated fluid balance and body weight change were charted preoperatively and
      daily at the same time during a postoperative period of 6 days. Differences were
      calculated by subtracting cumulated fluid balance from body weight change (1 g =
      1 mL), and agreement was assessed by making Bland-Altman plots as well as Pearson
      correlations. RESULTS: From day 1 to 4, the mean difference between cumulated
      fluid balance and body weight change was below 0.4 kg/L. On day 5 and 6, the
      discrepancies increased with mean differences of, respectively, 1.2 kg/L (p <
      0.002*) and 2 kg/L (p < 0.0001*). Bland-Altman plots showed increasingly poor
      agreement for all postoperative days with wide limits of agreement, ranging from
      more than 6 kg/L to almost 10 kg/L. Pearson correlations were moderate to strong
      at all times ranging from 0.437 (day 1) to 0.758 (day 4). CONCLUSIONS: The
      accordance between cumulated fluid balance and body weight change for colorectal
      surgical patients is relatively good for the first four postoperative days,
      however, with large uncertainty, whereas on the fifth and sixth postoperative
      day, the discrepancy is statistically and clinically significant. The fluid chart
      cannot stand alone in interpretation of the patient's fluid balance; body weight
      and clinical judgment is indispensable.

PMID- 25070945
TI  - Differences in correlates of condom use between young adults and adults attending
      sexually transmitted infection clinics.
AB  - Despite developmental differences between young adults and adults, studies of
      condom use have not typically considered young adults as a distinct age group.
      This study sought to examine how condom use and its correlates differed between
      high-risk young adults and adults. Sexually transmitted infection (STI) clinic
      patients (n = 763) reported STI history, contraception, negative condom
      attitudes, fear of partner reaction to condom use and risky behaviours. Past 3
      month condom use was examined as unprotected vaginal sex (UVS) acts, proportional
      condom use and consistent condom use. Regression models tested associations of
      age group and potential correlates with each condom use outcome. Interaction
      models tested whether associations differed by age group. Proportional condom use
      was greater in young adults than adults (mean 0.55 vs. 0.47); UVS and consistent
      condom use were similar between age groups. Young adults with a recent STI
      reported less condom use, whereas for older adults, a distant STI was associated
      with less condom use, compared to others in their age groups. Negative condom
      attitudes were more strongly linked to UVS acts for younger versus older adults.
      STI prevention efforts for younger adults may be improved by intensifying
      counselling about condom use immediately following STI diagnosis and targeting
      negative condom attitudes. 

PMID- 25070946
TI  - Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid
      polymorphisms in Asian and European populations.
AB  - Previous studies have emphasized ethnically heterogeneous human leukocyte antigen
      (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine
      mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782
      seropositive RA cases and 4315 controls of Asian descent. We applied imputation
      to determine genotypes for eight class I and II HLA genes to Asian populations
      for the first time using a newly constructed pan-Asian reference panel. First, we
      empirically measured high imputation accuracy in Asian samples. Then we observed
      the most significant association in HLA-DRbeta1 at amino acid position 13,
      located outside the classical shared epitope (Pomnibus = 6.9 * 10(-135)). The
      individual residues at position 13 have relative effects that are consistent with
      published effects in European populations (His > Phe > Arg > Tyr ? Gly > Ser)-
      but the observed effects in Asians are generally smaller. Applying stepwise
      conditional analysis, we identified additional independent associations at
      positions 57 (conditional Pomnibus = 2.2 * 10(-33)) and 74 (conditional Pomnibus
      = 1.1 * 10(-8)). Outside of HLA-DRbeta1, we observed independent effects for
      amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8 * 10(-6)) and
      HLA-DPbeta1 (Phe9, conditional P = 3.0 * 10(-5)) concordant with European
      populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common
      set of amino acid residues confer shared effects in European and Asian
      populations and (ii) these same effects can explain ethnically heterogeneous
      classical allelic associations (e.g. HLA-DRB1*09:01) due to allele frequency
      differences between populations. Our study illustrates the value of high
      resolution imputation for fine-mapping causal variants in the MHC.

PMID- 25070947
TI  - Neuronal NF1/RAS regulation of cyclic AMP requires atypical PKC activation.
AB  - Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder in which
      affected individuals are prone to learning, attention and behavioral problems.
      Previous studies in mice and flies have yielded conflicting results regarding the
      specific effector pathways responsible for NF1 protein (neurofibromin) regulation
      of neuronal function, with both cyclic AMP (cAMP)- and RAS-dependent mechanisms
      described. Herein, we leverage a combination of induced pluripotent stem cell
      derived NF1 patient neural progenitor cells and Nf1 genetically engineered mice
      to establish, for the first time, that neurofibromin regulation of cAMP requires
      RAS activation in human and mouse neurons. However, instead of involving RAS
      mediated MEK/AKT signaling, RAS regulation of cAMP homeostasis operates through
      the activation of atypical protein kinase C zeta, leading to GRK2-driven Galphas
      inactivation. These findings reveal a novel mechanism by which RAS can regulate
      cAMP levels in the mammalian brain. 

PMID- 25070948
TI  - Excess SMAD signaling contributes to heart and muscle dysfunction in muscular
      dystrophy.
AB  - Disruption of the dystrophin complex causes muscle injury, dysfunction, cell
      death and fibrosis. Excess transforming growth factor (TGF) beta signaling has
      been described in human muscular dystrophy and animal models, where it is thought
      to relate to the progressive fibrosis that characterizes dystrophic muscle. We
      now found that canonical TGFbeta signaling acutely increases when dystrophic
      muscle is stimulated to contract. Muscle lacking the dystrophin-associated
      protein gamma-sarcoglycan (Sgcg null) was subjected to a lengthening protocol to
      produce maximal muscle injury, which produced rapid accumulation of nuclear
      phosphorylated SMAD2/3. To test whether reducing SMAD signaling improves muscular
      dystrophy in mice, we introduced a heterozygous mutation of SMAD4 (S4) into Sgcg
      mice to reduce but not ablate SMAD4. Sgcg/S4 mice had improved body mass compared
      with Sgcg mice, which normally show a wasting phenotype similar to human muscular
      dystrophy patients. Sgcg/S4 mice had improved cardiac function as well as
      improved twitch and tetanic force in skeletal muscle. Functional enhancement in
      Sgcg/S4 muscle occurred without a reduction in fibrosis, suggesting that
      intracellular SMAD4 targets may be important. An assessment of genes
      differentially expressed in Sgcg muscle focused on those encoding calcium
      handling proteins and responsive to TGFbeta since this pathway is a target for
      mediating improvement in muscular dystrophy. These data demonstrate that
      excessive TGFbeta signaling alters cardiac and muscle performance through the
      intracellular SMAD pathway. 

PMID- 25070950
TI  - A dynamic network of estrogen receptors in murine lymphocytes: fine-tuning the
      immune response.
AB  - The actual level of circulating estrogen (17beta-estradiol, E2) has a serious
      impact on regulation of diverse immune cell functions, where their classical
      cytoplasmic receptors, ERalpha and ERbeta, act as nuclear transcriptional
      regulators of multiple target genes. There is growing evidence, however, for
      rapid, "non-nuclear" regulatory effects of E2 on lymphocytes. Such effects are
      likely mediated by putative membrane-associated receptor(s) (mER), but the
      mechanistic details and the involved signaling pathways still remained largely
      unknown because of their complexity. Here, we show that in lymphocytes, mERs can
      signalize themselves, and upon ligation, they are able to coordinate
      translocation of other E2Rs to the PM. Our data firmly imply existence of a
      complex, dynamic network of at least seven ER forms in murine lymphocytes:
      cytoplasmic and membrane-linked forms of ERalpha, ERbeta, or GPR30 and a mER that
      can receive extracellular E2 signals. The latter mERs are likely palmitoylated,
      as they are enriched in lipid-raft microdomains, and their E2 binding is also
      cholesterol dependent. The data also support that ligation of mERs can induce
      rapid regulatory signals to lymphocytes and then internalize and let the E2
      liberate in lysosomes. In addition, they can dynamically control the cell-surface
      linkage of other cytoplasmic ERs. As demonstrated by the differential effects of
      mER or cytoplasmic ER ligation on the proliferation of activated T and B
      lymphocytes, such a dynamic E2R network can be considered as a tool to manage
      accommodation/fine-tuning of lymphocytes to rapidly changing hormone levels.

PMID- 25070949
TI  - Lipid rafts couple class A scavenger receptors to phospholipase A2 activation
      during macrophage adhesion.
AB  - SR-A mediated macrophage adhesion to modified ECM proteins in a process that
      involves physical attachment of SR-A to modified ECM and activation of Lyn-PI3K
      and PLA2-12/15-lipoxygenase signaling pathways. Structurally, SR-A-mediated cell
      adhesion requires a 6-aa membrane-proximal cytoplasmic motif. However, the
      mechanism that couples SR-A-mediated adhesion to activation of these distinct
      signaling pathways is not known. For other adhesion receptors, including
      integrins, localization in cholesterol-rich LRs is an important mechanism for
      coupling the receptor with the activation of specific signaling pathways. We
      hypothesized that SR-A-mediated macrophage adhesion might also involve LRs. Our
      results demonstrate that SR-A is enriched in LRs in HEK cells that heterologously
      express SR-A and in macrophages that endogenously expressed the receptor. We
      further show that a truncated SR-A construct (SR-A(Delta1-49)), which mediates
      cell adhesion but not ligand internalization, is also enriched in LRs, suggesting
      an association between LRs and SR-A-dependent cell adhesion. To examine this
      association more directly, we used the cholesterol chelator MbetaCD to deplete
      cholesterol and disrupt LR function. We found that cholesterol depletion
      significantly decreased SR-A-mediated macrophage adhesion. We further show that
      decreased SR-A-dependent macrophage adhesion following cholesterol depletion
      results from the inhibition of PLA2 but not PI3K activation. Overall, our results
      demonstrate an important role for LRs in selectively coupling SR-A with PLA2
      activation during macrophage adhesion.

PMID- 25070951
TI  - Should Authors Revise a Rejected Manuscript Prior to Submitting to a New Journal?

PMID- 25070953
TI  - A sterol-enriched vacuolar microdomain mediates stationary phase lipophagy in
      budding yeast.
AB  - Stationary phase (stat-phase) is a poorly understood physiological state under
      which cells arrest proliferation and acquire resistance to multiple stresses.
      Lipid droplets (LDs), organelles specialized for cellular lipid homeostasis,
      increase in size and number at the onset of stat-phase. However, little is known
      about the dynamics of LDs under this condition. In this paper, we reveal the
      passage of LDs from perinuclear endoplasmic reticulum association to entry into
      vacuoles during the transition to stat-phase. We show that the process requires
      the core autophagy machinery and a subset of autophagy-related (Atg) proteins
      involved in selective autophagy. Notably, the process that we term stat-phase
      lipophagy is mediated through a sterol-enriched vacuolar microdomain whose
      formation and integrity directly affect LD translocation. Intriguingly, cells
      defective in stat-phase lipophagy showed disrupted vacuolar microdomains,
      implying that LD contents, likely sterol esters, contribute to the maintenance of
      vacuolar microdomains. Together, we propose a feed-forward loop in which
      lipophagy stimulates vacuolar microdomain formation, which in turn promotes
      lipophagy during stat-phase. 

PMID- 25070952
TI  - Intestinal nuclear receptors in HDL cholesterol metabolism.
AB  - The intestine plays a pivotal role in cholesterol homeostasis by functioning as
      an absorptive and secretory organ in the reverse cholesterol transport pathway.
      Enterocytes control cholesterol absorption, apoAI synthesis, HDL biogenesis, and
      nonbiliary cholesterol fecal disposal. Thus, intestine-based therapeutic
      interventions may hold promise in the management of diseases driven by
      cholesterol overload. Lipid-sensing nuclear receptors (NRs) are highly expressed
      in the intestinal epithelium and regulate transcriptionally the handling of
      cholesterol by the enterocytes. Here, we discuss the NR regulation of cholesterol
      fluxes across the enterocytes with special emphasis on NR exploitation as a bona
      fide novel HDL-raising strategy. 

PMID- 25070954
TI  - TPX2 levels modulate meiotic spindle size and architecture in Xenopus egg
      extracts.
AB  - The spindle segregates chromosomes in dividing eukaryotic cells, and its assembly
      pathway and morphology vary across organisms and cell types. We investigated
      mechanisms underlying differences between meiotic spindles formed in egg extracts
      of two frog species. Small Xenopus tropicalis spindles resisted inhibition of two
      factors essential for assembly of the larger Xenopus laevis spindles: RanGTP,
      which functions in chromatin-driven spindle assembly, and the kinesin-5 motor
      Eg5, which drives antiparallel microtubule (MT) sliding. This suggested a role
      for the MT-associated protein TPX2 (targeting factor for Xenopus kinesin-like
      protein 2), which is regulated by Ran and binds Eg5. Indeed, TPX2 was threefold
      more abundant in X. tropicalis extracts, and elevated TPX2 levels in X. laevis
      extracts reduced spindle length and sensitivity to Ran and Eg5 inhibition. Higher
      TPX2 levels recruited Eg5 to the poles, where MT density increased. We propose
      that TPX2 levels modulate spindle architecture through Eg5, partitioning MTs
      between a tiled, antiparallel array that promotes spindle expansion and a cross
      linked, parallel architecture that concentrates MTs at spindle poles. 

PMID- 25070955
TI  - Radial intercalation is regulated by the Par complex and the microtubule
      stabilizing protein CLAMP/Spef1.
AB  - The directed movement of cells is critical for numerous developmental and disease
      processes. A developmentally reiterated form of migration is radial
      intercalation; the process by which cells move in a direction orthogonal to the
      plane of the tissue from an inner layer to an outer layer. We use the radial
      intercalation of cells into the skin of Xenopus laevis embryos as a model to
      study directed cell migration within an epithelial tissue. We identify a novel
      function for both the microtubule-binding protein CLAMP and members of the
      microtubule-regulating Par complex during intercalation. Specifically, we show
      that Par3 and aPKC promote the apical positioning of centrioles, whereas CLAMP
      stabilizes microtubules along the axis of migration. We propose a model in which
      the Par complex defines the orientation of apical migration during intercalation
      and in which subcellular localization of CLAMP promotes the establishment of an
      axis of microtubule stability required for the active migration of cells into the
      outer epithelium. 

PMID- 25070958
TI  - Race/Ethnic differences in the risk of hemorrhagic complications among patients
      with ischemic stroke receiving thrombolytic therapy.
AB  - BACKGROUND AND PURPOSE: Race/ethnic-related differences in safety of intravenous
      thrombolytic therapy have been shown in patients with myocardial infarction, but
      not studied in ischemic stroke. METHODS: Using data from the Get With The
      Guidelines (GWTG)-Stroke program (n=54 334), we evaluated differences in risk
      adjusted bleeding rates (any, symptomatic intracerebral hemorrhage [sICH],
      serious life-threatening [excluding sICH], or other) and mortality in white (n=40
      411), black (n=8243), Hispanic (n=4257), and Asian (n=1523) patients receiving
      intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke.
      RESULTS: Compared with white patients, overall adjusted hemorrhagic complications
      after tPA were higher in black (odds ratio, 1.14, 95% confidence interval, 1.04
      1.28) and Asian (odds ratio, 1.36, 95% confidence interval, 1.14-1.61) patients.
      Overall adjusted bleeding complications in Hispanics were similar to those of
      whites. Increased risk of overall bleeding in Asians was related to higher risk
      of adjusted sICH (odds ratio, 1.47, 95% confidence interval, 1.19-1.82), whereas
      in blacks, it was related to higher risk of other bleeding. No significant race
      related difference was noted in risk of serious or life-threatening bleeding or
      in overall mortality or death in patients with sICH or any hemorrhagic
      complications. CONCLUSIONS: In patients with stroke receiving tPA, hemorrhagic
      complications were slightly higher in blacks and Asians, but not in Hispanics
      compared with whites. Asians also faced significantly higher risk for sICH
      relative to other race/ethnic groups. Future studies are needed to evaluate
      whether reduction in tPA dose similar to that used in many Asian countries could
      improve the safety of tPA therapy in Asians in the United States with acute
      ischemic strokes while maintaining efficacy.

PMID- 25070956
TI  - Paxillin inhibits HDAC6 to regulate microtubule acetylation, Golgi structure, and
      polarized migration.
AB  - Polarized cell migration is essential for normal organism development and is also
      a critical component of cancer cell invasion and disease progression. Directional
      cell motility requires the coordination of dynamic cell-extracellular matrix
      interactions as well as repositioning of the Golgi apparatus, both of which can
      be controlled by the microtubule (MT) cytoskeleton. In this paper, we have
      identified a new and conserved role for the focal adhesion scaffold protein
      paxillin in regulating the posttranslational modification of the MT cytoskeleton
      through an inhibitory interaction with the alpha-tubulin deacetylase HDAC6. We
      also determined that through HDAC6-dependent regulation of the MT cytoskeleton,
      paxillin regulates both Golgi organelle integrity and polarized cell invasion and
      migration in both three-dimensional and two-dimensional matrix microenvironments.
      Importantly, these data reveal a fundamental role for paxillin in coordinating MT
      acetylation-dependent cell polarization and migration in both normal and
      transformed cells. 

PMID- 25070959
TI  - Persistent cognitive impairment after transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: By definition, the symptoms of a transient ischemic
      attack (TIA) subside completely within 24 hours. Imaging studies show signs of
      persistent ischemic tissue damage in a substantial amount of patients with TIA.
      Cerebral infarction can cause permanent cognitive impairment. Whether permanent
      cognitive impairment occurs after TIA is unclear, as is its profile. METHODS:
      Patients with TIA aged 45 to 65 years without prior stroke or dementia underwent
      comprehensive neuropsychological testing within 3 months. Z scores per cognitive
      domain were obtained, based on the mean of a control group within the same age
      range. Cognitive impairment was defined as a domain z score <-1.65. Patients
      underwent either computed tomography or MRI brain imaging. RESULTS: One hundred
      seven patients with TIA (63% women, mean age, 56.6 years) were included and
      compared with 81 controls (56% women, mean age, 52.9 years). Patients performed
      worse on all cognitive domains except episodic memory. Working memory (25%),
      attention (22%), and information processing speed (16%) were most frequently
      impaired and more often than in the control group (age- and sex-adjusted odds
      ratios, respectively, 22.5 [95% confidence interval, 2.9-174.3], 6.8 [1.9-24.3],
      7.1 [1.5-32.5]). More than 35% of patients with TIA had impairment of >=1
      cognitive domain. Presence of silent brain infarcts was related to worse
      executive functioning but did not explain the whole relationship between TIA and
      cognitive impairment. CONCLUSIONS: More than a third of patients with TIA have
      impairment of >=1 cognitive domain within 3 months after their TIA. The affected
      domains fit in the vascular cognitive impairment profile.

PMID- 25070960
TI  - Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis
      progression in patients with cerebrovascular disease of ischemic origin: a
      randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Thromboxane prostaglandin receptors have been implicated
      to be involved in the atherosclerotic process. We assessed whether Terutroban, a
      thromboxane prostaglandin receptor antagonist, affects the progression of
      atherosclerosis, as measured by common carotid intima-media thickness and carotid
      plaques. METHODS: A substudy was performed among 1141 participants of the aspirin
      controlled Prevention of Cerebrovascular and Cardiovascular Events of Ischemic
      Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient
      Ischemic Attack (PERFORM) trial. Common carotid intima-media thickness and
      carotid plaque occurrence was measured during a 3-year period. RESULTS: Baseline
      characteristics did not differ between Terutroban (n=592) and aspirin (n=549)
      treated patients and were similar as in the main study. Mean study and treatment
      duration were similar (28 and 25 months, respectively). In the Terutroban group,
      the annualized rate of change in common carotid intima-media thickness was 0.006
      mm per year (95% confidence interval, -0.004 to 0.016) and -0.005 mm per year
      (95% confidence interval, -0.015 to 0.005) in the aspirin group. There was no
      statistically significant difference between the groups in the annualized rate of
      change of common carotid intima-media thickness (0.011 mm per year; 95%
      confidence interval, -0.003 to 0.025). At 12 months of follow-up, 66% of
      Terutroban patients had no emergent plaques, 31% had 1 to 2 emergent plaques, and
      3% had >=3 emergent plaques. In the aspirin group, the corresponding percentages
      were 64%, 32%, and 4%. Over time, there was no statistically significant
      difference in the number of emergent carotid plaques between treatment modalities
      (rate ratio, 0.91; 95% confidence interval, 0.77-1.07). CONCLUSIONS: Compared
      with aspirin, Terutroban did not beneficially affect progression of carotid
      atherosclerosis among well-treated patients with a history of ischemic stroke or
      transient ischemic attacks with an internal carotid stenosis <70%. CLINICAL TRIAL
      REGISTRATION URL: http://www.controlled-trials.com. Unique identifier:
      ISRCTN66157730.

PMID- 25070961
TI  - Predictors and biomarkers of treatment gains in a clinical stroke trial targeting
      the lower extremity.
AB  - BACKGROUND AND PURPOSE: Behavioral measures are often used to distinguish
      subgroups of patients with stroke (eg, to predict treatment gains, stratify
      clinical trial enrollees, or select rehabilitation therapy). In studies of the
      upper extremity, measures of brain function using functional magnetic resonance
      imaging (fMRI) have also been found useful, but this approach has not been
      examined for the lower extremity. The current study hypothesized that an fMRI
      based measure of cortical function would significantly improve prediction of
      treatment-induced lower extremity behavioral gains. Biomarkers of treatment gains
      were also explored. METHODS: Patients with hemiparesis 1 to 12 months after
      stroke were enrolled in a double-blind, placebo-controlled, randomized clinical
      trial of ropinirole+physical therapy versus placebo+physical therapy, results of
      which have previously been reported (NCT00221390).(15) Primary end point was
      change in gait velocity. Enrollees underwent baseline multimodal assessment that
      included 19 measures spanning 5 assessment categories (medical history,
      impairment, disability, brain injury, and brain function), and also underwent
      reassessment 3 weeks after end of therapy. RESULTS: In bivariate analysis, 8
      baseline measures belonging to 4 categories (medical history, impairment,
      disability, and brain function) significantly predicted change in gait velocity.
      Prediction was strongest, however, using a multivariate model containing 2
      measures (leg Fugl-Meyer score and fMRI activation volume within ipsilesional
      foot sensorimotor cortex). Increased activation volume within bilateral foot
      primary sensorimotor cortex correlated positively with treatment-induced leg
      motor gains. CONCLUSIONS: A multimodal model incorporating behavioral and fMRI
      measures best predicted treatment-induced changes in gait velocity in a clinical
      trial setting. Results also suggest potential use of fMRI measures as biomarkers
      of treatment gains.

PMID- 25070962
TI  - ATP-evoked sustained vasoconstrictions mediated by heteromeric P2X1/4 receptors
      in cerebral arteries.
AB  - BACKGROUND AND PURPOSE: Current knowledge states that vasoconstrictor responses
      to ATP are mediated by rapidly desensitizing ligand-gated P2X1 receptors in
      vascular smooth muscle cells (VSMCs). However, ATP is implicated in contributing
      to pathological conditions involving sustained vasoconstrictor response such as
      cerebral vasospasm. The purpose of this study is to test the hypothesis that the
      stimulation of VSMC P2XR receptors (P2XRs) contributes to ATP-evoked sustained
      vasoconstrictions in rat middle cerebral arteries (RMCAs). METHODS: Reverse
      transcription- polymerase chain reaction, Western blot, and immunocytochemistry
      were used to analyze expression of mRNA and proteins in RMCAs VSMCs. Ionic
      currents and calcium responses were investigated using patch-clamp and confocal
      imaging techniques, respectively. Functional responses were confirmed using wire
      myography. RESULTS: Expression of mRNA and protein for P2X1R and P2X4R subunits
      was identified in RMCA VSMCs. Confocal imaging in fluo-3-loaded VSMCs showed that
      ATP and a selective P2XR agonist, alphabetameATP, evoked similar dose-dependent
      increases in [Ca(2+)]i. Patch-clamp experiments identified 2 components of P2XR
      mediated currents: consisting of a fast desensitizing phase mediated by homomeric
      P2X1Rs and a slowly desensitizing phase involving heteromeric P2X1/4Rs. Isometric
      tension measurements showed that ~80%:20% of initial ATP-evoked vasoconstriction
      in RMCA is mediated by homomeric P2X1Rs and heteromeric P2X1/4Rs, respectively.
      The sustained slowly desensitizing and rapidly recovering from desensitization
      responses are mediated by heteromeric P2X1/4Rs. CONCLUSIONS: This study reveals
      for the first time that apart from rapidly desensitizing homomeric P2X1Rs,
      heteromeric P2X1/4Rs contribute to the sustained component of the purinergic
      mediated vasoconstriction in RMCA. Our study, therefore, identifies possible
      novel targets for therapeutical intervention in cerebral circulation.

PMID- 25070963
TI  - Novel factor xa inhibitor for the treatment of cerebral venous and sinus
      thrombosis: first experience in 7 patients.
AB  - BACKGROUND AND PURPOSE: Thrombosis of cerebral veins and sinus (cerebral venous
      thrombosis) is a rare stroke pathogenesis. Pharmaceutical treatment is restricted
      to heparin and oral anticoagulation with vitamin K antagonists (VKAs). METHODS:
      Between January 2012 and December 2013, we recorded data from our patients with
      cerebral venous thrombosis. The modified Rankin scale was used to assess clinical
      severity; excellent outcome was defined as modified Rankin scale 0 to 1.
      Recanalization was assessed on follow-up MR angiography. Patients were then
      divided into 2 treatment groups: phenprocoumon (VKA) and a novel factor Xa
      inhibitor. Clinical and radiological baseline data, outcome, recanalization
      status, and complications were retrospectively compared. RESULTS: Sixteen
      patients were included, and 7 were treated with rivaroxaban. Overall outcome was
      excellent in 93.8%, and all patients showed at least partial recanalization. No
      statistical significant differences were found between the groups, except the use
      of heparin before start of oral anticoagulation (P=0.03). One patient in the VKA
      and 2 patients in the factor Xa inhibitor group had minor bleeding (P=0.55)
      within the median (range) follow-up of 8 months (5-26). CONCLUSIONS: Factor Xa
      inhibitor showed a similar clinical benefit as VKA in the treatment of cerebral
      venous thrombosis. Further systematic prospective evaluation is warranted.

PMID- 25070964
TI  - Republished: Society for Neuroscience in Anesthesiology and Critical Care expert
      consensus statement: Anesthetic management of endovascular treatment for acute
      ischemic stroke.
AB  - Literature on the anesthetic management of endovascular treatment of acute
      ischemic stroke (AIS) is limited. Anesthetic management during these procedures
      is still mostly dependent on individual or institutional preferences. Thus, the
      Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a
      task force to provide expert consensus recommendations on anesthetic management
      of endovascular treatment of AIS. The task force conducted a systematic
      literature review (up to August 2012). Because of the limited number of research
      articles relating to this subject, the task force solicited opinions from experts
      in this area. The task force created a draft consensus statement based on the
      available data. Classes of recommendations and levels of evidence were assigned
      to articles specifically addressing anesthetic management during endovascular
      treatment of stroke using the standard American Heart Association evidence rating
      scheme. The draft consensus statement was reviewed by the Task Force, SNACC
      Executive Committee and representatives of Society of NeuroInterventional Surgery
      (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final
      document. For this consensus statement the anesthetic management of endovascular
      treatment of AIS was subdivided into 12 topics. Each topic includes a summary of
      available data followed by recommendations. This consensus statement is intended
      for use by individuals involved in the care of patients with acute ischemic
      stroke, such as anesthesiologists, interventional neuroradiologists,
      neurologists, neurointensivists and neurosurgeons. 

PMID- 25070968
TI  - Pregnancy health problems and low birth weight associated with maternal insecure
      attachment style.
AB  - We aimed to determine the association between attachment style and health
      problems during pregnancy, as well as perinatal health variables. In 122 mothers
      who were 2-18 months postpartum, hot flushes, vaginal discharge, back pain,
      breast tenderness, hair changes, and psychological problems were shown to be
      associated with insecure attachment as measured by the Adult Attachment Style
      Questionnaires. Babies born to mothers with insecure attachment were more likely
      to have a low birth weight. It is vital to increase awareness of insecure
      attachment style as a risk factor among perinatal health care providers to
      optimize services.

PMID- 25070967
TI  - Randomized trial of DVD, telephone, and usual care for increasing mammography
      adherence.
AB  - The purpose of this study was to test an intervention to increase mammography
      screening in women 51-75 years of age who had not received a mammogram in the
      last 15 months. A total of 1681 women were randomized to (1) a mailed tailored
      interactive DVD, (2) a computer-tailored telephone counseling, or (3) usual care.
      Women with income below US$75,000 who were in the interactive DVD group had
      significantly more mammograms than women in usual care. Women with income above
      US$75,000 had significantly fewer mammograms than women with income less than
      US$75,000 regardless of group. Further investigation is needed to understand why
      women with income above US$75,000 did not show the same benefit of the
      intervention.

PMID- 25070969
TI  - MDM2 oncogene, E3 ubiquitin protein ligase T309G polymorphism and risk of
      oesophageal or gastric cancer: meta-analysis of 15 studies.
AB  - OBJECTIVE: To investigate the association between potentially functional MDM2
      oncogene, E3 ubiquitin protein ligase (MDM2) T309G polymorphism and
      susceptibility to oesophageal or gastric cancer. METHODS: Two investigators
      independently searched the PubMed and Chinese National Knowledge Infrastructure
      databases for studies published before September 2013. RESULTS: Pooled results
      showed that the variant homozygous 309 GG genotype (versus TT) was significantly
      associated with increased risk of both oesophageal (odds ratio [OR] 0.77; 95%
      confidence interval [CI] 0.65, 0.90) and gastric cancer (OR 0.52; 95% CI 0.38,
      0.72). Subgroup analysis revealed a 309 GG-associated increased risk for both
      cancer types in Asian populations, particularly among Chinese and Japanese
      ethnicity. When stratified for Helicobacter pylori infection and histological
      type of gastric cancer, the 309 GG-related risk was higher in H. pylori-positive
      patients (T versus G: OR 0.37; 95% CI 0.22, 0.63) and the association was
      stronger with intestinal (TT + TG versus GG: OR 0.68; 95% CI 0.54, 0.87) rather
      than diffuse gastric-cancer type. CONCLUSIONS: The MDM2 T309G polymorphism may be
      significantly associated with increased susceptibility to oesophageal or gastric
      cancer, particularly among Eastern Asian populations.

PMID- 25070971
TI  - Borneo and Indochina are major evolutionary hotspots for Southeast Asian
      biodiversity.
AB  - Tropical Southeast (SE) Asia harbors extraordinary species richness and in its
      entirety comprises four of the Earth's 34 biodiversity hotspots. Here, we examine
      the assembly of the SE Asian biota through time and space. We conduct meta
      analyses of geological, climatic, and biological (including 61 phylogenetic) data
      sets to test which areas have been the sources of long-term biological diversity
      in SE Asia, particularly in the pre-Miocene, Miocene, and Plio-Pleistocene, and
      whether the respective biota have been dominated by in situ diversification,
      immigration and/or emigration, or equilibrium dynamics. We identify Borneo and
      Indochina, in particular, as major "evolutionary hotspots" for a diverse range of
      fauna and flora. Although most of the region's biodiversity is a result of both
      the accumulation of immigrants and in situ diversification, within-area
      diversification and subsequent emigration have been the predominant signals
      characterizing Indochina and Borneo's biota since at least the early Miocene. In
      contrast, colonization events are comparatively rare from younger volcanically
      active emergent islands such as Java, which show increased levels of immigration
      events. Few dispersal events were observed across the major biogeographic barrier
      of Wallace's Line. Accelerated efforts to conserve Borneo's flora and fauna in
      particular, currently housing the highest levels of SE Asian plant and mammal
      species richness, are critically required. 

PMID- 25070972
TI  - Mitochondrial phylogenomics of early land plants: mitigating the effects of
      saturation, compositional heterogeneity, and codon-usage bias.
AB  - Phylogenetic analyses using concatenation of genomic-scale data have been seen as
      the panacea for resolving the incongruences among inferences from few or single
      genes. However, phylogenomics may also suffer from systematic errors, due to the,
      perhaps cumulative, effects of saturation, among-taxa compositional (GC content)
      heterogeneity, or codon-usage bias plaguing the individual nucleotide loci that
      are concatenated. Here, we provide an example of how these factors affect the
      inferences of the phylogeny of early land plants based on mitochondrial genomic
      data. Mitochondrial sequences evolve slowly in plants and hence are thought to be
      suitable for resolving deep relationships. We newly assembled mitochondrial
      genomes from 20 bryophytes, complemented these with 40 other streptophytes (land
      plants plus algal outgroups), compiling a data matrix of 60 taxa and 41
      mitochondrial genes. Homogeneous analyses of the concatenated nucleotide data
      resolve mosses as sister-group to the remaining land plants. However, the
      corresponding translated amino acid data support the liverwort lineage in this
      position. Both results receive weak to moderate support in maximum-likelihood
      analyses, but strong support in Bayesian inferences. Tests of alternative
      hypotheses using either nucleotide or amino acid data provide implicit support
      for their respective optimal topologies, and clearly reject the hypotheses that
      bryophytes are monophyletic, liverworts and mosses share a unique common
      ancestor, or hornworts are sister to the remaining land plants. We determined
      that land plant lineages differ in their nucleotide composition, and in their
      usage of synonymous codon variants. Composition heterogeneous Bayesian analyses
      employing a nonstationary model that accounts for variation in among-lineage
      composition, and inferences from degenerated nucleotide data that avoid the
      effects of synonymous substitutions that underlie codon-usage bias, again
      recovered liverworts being sister to the remaining land plants but without
      support. These analyses indicate that the inference of an early-branching moss
      lineage based on the nucleotide data is caused by convergent compositional
      biases. Accommodating among-site amino acid compositional heterogeneity (CAT
      model) yields no support for the optimal resolution of liverwort as sister to the
      rest of land plants, suggesting that the robust inference of the liverwort
      position in homogeneous analyses may be due in part to compositional biases among
      sites. All analyses support a paraphyletic bryophytes with hornworts composing
      the sister-group to tracheophytes. We conclude that while genomic data may
      generate highly supported phylogenetic trees, these inferences may be artifacts.
      We suggest that phylogenomic analyses should assess the possible impact of
      potential biases through comparisons of protein-coding gene data and their amino
      acid translations by evaluating the impact of substitutional saturation,
      synonymous substitutions, and compositional biases through data deletion
      strategies and by analyzing the data using heterogeneous composition models. We
      caution against relying on any one presentation of the data (nucleotide or amino
      acid) or any one type of analysis even when analyzing large-scale data sets, no
      matter how well-supported, without fully exploring the effects of substitution
      models. 

PMID- 25070973
TI  - Easy bruising in a patient with secondary amenorrhea.

PMID- 25070970
TI  - The inference of gene trees with species trees.
AB  - This article reviews the various models that have been used to describe the
      relationships between gene trees and species trees. Molecular phylogeny has
      focused mainly on improving models for the reconstruction of gene trees based on
      sequence alignments. Yet, most phylogeneticists seek to reveal the history of
      species. Although the histories of genes and species are tightly linked, they are
      seldom identical, because genes duplicate, are lost or horizontally transferred,
      and because alleles can coexist in populations for periods that may span several
      speciation events. Building models describing the relationship between gene and
      species trees can thus improve the reconstruction of gene trees when a species
      tree is known, and vice versa. Several approaches have been proposed to solve the
      problem in one direction or the other, but in general neither gene trees nor
      species trees are known. Only a few studies have attempted to jointly infer gene
      trees and species trees. These models account for gene duplication and loss,
      transfer or incomplete lineage sorting. Some of them consider several types of
      events together, but none exists currently that considers the full repertoire of
      processes that generate gene trees along the species tree. Simulations as well as
      empirical studies on genomic data show that combining gene tree-species tree
      models with models of sequence evolution improves gene tree reconstruction. In
      turn, these better gene trees provide a more reliable basis for studying genome
      evolution or reconstructing ancestral chromosomes and ancestral gene sequences.
      We predict that gene tree-species tree methods that can deal with genomic data
      sets will be instrumental to advancing our understanding of genomic evolution. 

PMID- 25070974
TI  - Commentary.

PMID- 25070975
TI  - Commentary.

PMID- 25070976
TI  - A 9-year-old child with methemoglobinemia.

PMID- 25070977
TI  - An unusual electrophoresis.

PMID- 25070978
TI  - Big data diagnostics.

PMID- 25070979
TI  - AACC's Society for Young Clinical Laboratorians (SYCL) celebrates 10-year
      anniversary with t-shirt design contest.

PMID- 25070980
TI  - The aesthetics of libraries and reading rooms.

PMID- 25070981
TI  - Ovarian xenobiotic biotransformation enzymes are altered during phosphoramide
      mustard-induced ovotoxicity.
AB  - The anti-neoplastic prodrug, cyclophosphamide, requires biotransformation to
      phosphoramide mustard (PM), which partitions to volatile chloroethylaziridine
      (CEZ). PM and CEZ are ovotoxicants, however their ovarian biotransformation
      remains ill-defined. This study investigated PM and CEZ metabolism mechanisms
      through the utilization of cultured postnatal day 4 (PND4) Fisher 344 (F344) rat
      ovaries exposed to vehicle control (1% dimethyl sulfoxide (DMSO)) or PM (60MUM)
      for 2 or 4 days. Quantification of mRNA levels via an RT(2) profiler PCR array
      and target-specific RT-PCR along with Western blotting found increased mRNA and
      protein levels of xenobiotic metabolism genes including microsomal epoxide
      hydrolase (Ephx1) and glutathione S-transferase isoform pi (Gstp). PND4 ovaries
      were treated with 1% DMSO, PM (60MUM), cyclohexene oxide to inhibit EPHX1 (CHO;
      2mM), or PM + CHO for 4 days. Lack of functional EPHX1 increased PM-induced
      ovotoxicity, suggesting a detoxification role for EPHX1. PND4 ovaries were also
      treated with 1% DMSO, PM (60MUM), BSO (Glutathione (GSH) depletion; 100MUM), GEE
      (GSH supplementation; 2.5mM), PM +/- BSO, or PM +/- GEE for 4 days. GSH
      supplementation prevented PM-induced follicle loss, whereas no impact of GSH
      depletion was observed. Lastly, the effect of ovarian GSH on CEZ liberation and
      ovotoxicity was evaluated. Both untreated and GEE-treated PND4 ovaries were
      plated adjacent to ovaries receiving PM + GEE or PM + BSO treatments. Less CEZ
      induced ovotoxicity was observed with both GEE and BSO treatments indicating
      reduced CEZ liberation from PM. Collectively, this study supports ovarian
      biotransformation of PM, thereby influencing the ovotoxicity that ensues. 

PMID- 25070983
TI  - The contribution of dynamic changes in photosynthesis to shade tolerance of two
      conifer species.
AB  - Generally 'shade tolerance' refers to the capacity of a plant to exist at low
      light levels but characteristics of shade can vary and must be taken into account
      in defining the term. We studied Abies amabilis Dougl. ex J.Forbes and Tsuga
      heterophylla (Raf.) Sarg. under a forest canopy in the northwest of the Olympic
      Peninsula, USA, which has low annual sunshine hours and frequent overcast days.
      Using BF3 sunshine sensors, we surveyed diffuse and total light received by
      saplings growing under a range of canopy openness up to 30%. We measured
      variation in photosynthetic capacity over the growing season and within days and
      estimated photosynthesis induction in relation to ambient light. Three components
      of shade tolerance are associated with variation in light climate: (i) Total
      light on the floor of an 88-year stand of naturally regenerated T. heterophylla
      was greater on overcast than clear days. Light on overcast days varied throughout
      the day sometimes with a cyclical pattern. (ii) Photosynthetic capacity, Amax,
      varied both through the growing season and within days. Amax was generally
      greater in the latter part of the growing season, being limited by temperature
      and stomatal conductance, gs, at times during the early part. Saplings in more
      shaded areas had lower Amax and in the latter part of the growing season Amax was
      found to decline from mid-afternoon. (iii) Two patterns of photosynthesis
      induction to increased light were found. In a mean ambient light of 139 MUmol m(
      2) s(-1), induction had a curvilinear response to a step increase in light with a
      mean time constant, tau, of 112.3 s. In a mean ambient light of 74 MUmol m(-2) s(
      1), induction had a two-part increase: one with tau1 of 11.3 s and the other with
      tau2 of 184.0 s. These are the smallest published values of tau to date. (iv)
      Both variation in photosynthetic capacity and induction are components of shade
      tolerance where light varies over time. Amax acclimates to seasonal and diurnal
      changes in light and varies between microenvironments. The rapid induction
      processes can cause a rapid response of photosynthesis to changes in diffuse or
      direct light.

PMID- 25070984
TI  - Advice varies for suspected Lyme disease.

PMID- 25070982
TI  - Repeated gestational exposure of mice to chlorpyrifos oxon is associated with
      paraoxonase 1 (PON1) modulated effects in maternal and fetal tissues.
AB  - Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP)
      insecticide chlorpyrifos, causes developmental neurotoxicity in humans and
      rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by
      PON1 levels and the human Q192R polymorphism. To examine how the Q192R
      polymorphism influences fetal toxicity associated with gestational CPO exposure,
      we measured enzyme inhibition and fetal-brain gene expression in wild-type
      (PON1(+/+)), PON1-knockout (PON1(-/-)), and tgHuPON1R192 and tgHuPON1Q192
      transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d
      CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of
      CPO exposure inhibited in maternal tissues included brain acetylcholinesterase
      (AChE), red blood cell acylpeptide hydrolase (APH), and plasma
      butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was
      inhibited in PON1(-/-) and tgHuPON1Q192, but not PON1(+/+) or tgHuPON1R192 mice.
      Fetal brain AChE and plasma CES were inhibited in PON1(-/-) mice, but not in
      other genotypes. Weighted gene co-expression network analysis identified five
      gene modules based on clustering of the correlations among their fetal-brain
      expression values, allowing for correlation of module membership with the
      phenotypic data on enzyme inhibition. One module that correlated highly with
      maternal brain AChE activity had a large representation of homeobox genes. Gene
      set enrichment analysis revealed multiple gene sets affected by gestational CPO
      exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved
      in protein export, lipid metabolism, and neurotransmission. These data indicate
      that maternal PON1 status modulates the effects of repeated gestational CPO
      exposure on fetal-brain gene expression and on inhibition of both maternal and
      fetal biomarker enzymes. 

PMID- 25070985
TI  - Oil sands pollutants in traditional foods.

PMID- 25070986
TI  - Apologies in medicine: legal protection is not enough.

PMID- 25070987
TI  - Childhood Aleppo boil.

PMID- 25070988
TI  - Adding the head-tilt-chin-lift technique to adult compression-only CPR by
      untrained bystanders.

PMID- 25070990
TI  - Second BC drug safety scientist reinstated.

PMID- 25070989
TI  - Risk of vascular events in patients with polymyalgia rheumatica.
AB  - BACKGROUND: Polymyalgia rheumatica is one of the most common inflammatory
      rheumatologic conditions in older adults. Other inflammatory rheumatologic
      disorders are associated with an excess risk of vascular disease. We investigated
      whether polymyalgia rheumatica is associated with an increased risk of vascular
      events. METHODS: We used the General Practice Research Database to identify
      patients with a diagnosis of incident polymyalgia rheumatica between Jan. 1,
      1987, and Dec. 31, 1999. Patients were matched by age, sex and practice with up
      to 5 patients without polymyalgia rheumatica. Patients were followed until their
      first vascular event (cardiovascular, cerebrovascular, peripheral vascular) or
      the end of available records (May 2011). All participants were free of vascular
      disease before the diagnosis of polymyalgia rheumatica (or matched date). We used
      Cox regression models to compare time to first vascular event in patients with
      and without polymyalgia rheumatica. RESULTS: A total of 3249 patients with
      polymyalgia rheumatica and 12 735 patients without were included in the final
      sample. Over a median follow-up period of 7.8 (interquartile range 3.3-12.4)
      years, the rate of vascular events was higher among patients with polymyalgia
      rheumatica than among those without (36.1 v. 12.2 per 1000 person-years; adjusted
      hazard ratio 2.6, 95% confidence interval 2.4-2.9). The increased risk of a
      vascular event was similar for each vascular disease end point. The magnitude of
      risk was higher in early disease and in patients younger than 60 years at
      diagnosis. INTERPRETATION: Patients with polymyalgia rheumatica have an increased
      risk of vascular events. This risk is greatest in the youngest age groups. As
      with other forms of inflammatory arthritis, patients with polymyalgia rheumatica
      should have their vascular risk factors identified and actively managed to reduce
      this excess risk.

PMID- 25070991
TI  - Payment for plasma raises ethical issues.

PMID- 25070993
TI  - BC4GO: a full-text corpus for the BioCreative IV GO task.
AB  - Gene function curation via Gene Ontology (GO) annotation is a common task among
      Model Organism Database groups. Owing to its manual nature, this task is
      considered one of the bottlenecks in literature curation. There have been many
      previous attempts at automatic identification of GO terms and supporting
      information from full text. However, few systems have delivered an accuracy that
      is comparable with humans. One recognized challenge in developing such systems is
      the lack of marked sentence-level evidence text that provides the basis for
      making GO annotations. We aim to create a corpus that includes the GO evidence
      text along with the three core elements of GO annotations: (i) a gene or gene
      product, (ii) a GO term and (iii) a GO evidence code. To ensure our results are
      consistent with real-life GO data, we recruited eight professional GO curators
      and asked them to follow their routine GO annotation protocols. Our annotators
      marked up more than 5000 text passages in 200 articles for 1356 distinct GO
      terms. For evidence sentence selection, the inter-annotator agreement (IAA)
      results are 9.3% (strict) and 42.7% (relaxed) in F1-measures. For GO term
      selection, the IAAs are 47% (strict) and 62.9% (hierarchical). Our corpus
      analysis further shows that abstracts contain ~ 10% of relevant evidence
      sentences and 30% distinct GO terms, while the Results/Experiment section has
      nearly 60% relevant sentences and >70% GO terms. Further, of those evidence
      sentences found in abstracts, less than one-third contain enough experimental
      detail to fulfill the three core criteria of a GO annotation. This result
      demonstrates the need of using full-text articles for text mining GO annotations.
      Through its use at the BioCreative IV GO (BC4GO) task, we expect our corpus to
      become a valuable resource for the BioNLP research community. Database URL:
      http://www.biocreative.org/resources/corpora/bc-iv-go-task-corpus/.

PMID- 25070994
TI  - The ability to inoculate purified malaria sporozoites will accelerate vaccine and
      drug discovery.

PMID- 25070995
TI  - Controlled human malaria infection of Tanzanians by intradermal injection of
      aseptic, purified, cryopreserved Plasmodium falciparum sporozoites.
AB  - Controlled human malaria infection (CHMI) by mosquito bite has been used to
      assess anti-malaria interventions in > 1,500 volunteers since development of
      methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf)
      gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic,
      purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect
      Dutch volunteers by intradermal injection. We conducted a double-blind, placebo
      controlled trial to assess safety and infectivity of PfSPZ Challenge in adult
      male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or
      25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well
      tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and
      25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ
      groups geometric mean days from injection to Pf positivity by thick blood film
      was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no
      apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and
      infectious. 

PMID- 25070996
TI  - Clinical outcome and immune follow-up of different surgical approaches for human
      cyst hydatid disease in liver.
AB  - A new surgical approach (subadventitial cystectomy) has been developed for liver
      hydatid disease. We retrospectively compared clinical outcomes and immune status
      24 months after a subadventitial cystectomy with traditional surgical approaches.
      Patients with liver hydatid cysts were treated with a subadventitial cystectomy
      (N = 11), pericystectomy (N = 16), partial pericystectomy (N = 18), or hepatic
      resection (N = 12). By the end of the follow-up period, the subadventitial
      cystectomy group had the fewest post-operative complications and shortest
      hospital stays. Two recurrences occurred: one recurrence after partial
      pericystectomy and one recurrence after pericystectomy. The total immunoglobulin
      E (IgE) level decreased significantly in the subadventitial cystectomy group. The
      post-surgery IgG level was lower in the subadventitial cystectomy than the
      pericystectomy and partial pericystectomy groups. In conclusion, subadventitial
      cystectomy completely removes the parasite, causing lower complication rates and
      lower immune reactions. 

PMID- 25070997
TI  - Field investigations of winter transmission of eastern equine encephalitis virus
      in Florida.
AB  - Studies investigating winter transmission of Eastern equine encephalitis virus
      (EEEV) were conducted in Hillsborough County, Florida. The virus was detected in
      Culiseta melanura and Anopheles quadrimaculatus in February 2012 and 2013,
      respectively. During the winter months, herons were the most important avian
      hosts for all mosquito species encountered. In collections carried out in the
      summer of 2011, blood meals taken from herons were still common, but less
      frequently encountered than in winter, with an increased frequency of mammalian-
      and reptile-derived meals observed in the summer. Four wading bird species (Black
      crowned Night Heron [Nycticorax nycticorax], Yellow-crowned Night Heron
      [Nyctanassa violacea], Anhinga [Anhinga anhinga], and Great Blue Heron [Ardea
      herodias]) were most frequently fed upon by Cs. melanura and Culex erraticus,
      suggesting that these species may participate in maintaining EEEV during the
      winter in Florida. 

PMID- 25070998
TI  - Rationale for the coadministration of albendazole and ivermectin to humans for
      malaria parasite transmission control.
AB  - Recently there have been calls for the eradication of malaria and the elimination
      of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution,
      and STH infections are associated with increased risk for malaria. Indeed, there
      is evidence that suggests that STH infection may facilitate malaria transmission.
      Malaria and STH coinfection may exacerbate anemia, especially in pregnant women,
      leading to worsened child development and more adverse pregnancy outcomes than
      these diseases would cause on their own. Ivermectin mass drug administration
      (MDA) to humans for malaria parasite transmission suppression is being
      investigated as a potential malaria elimination tool. Adding albendazole to
      ivermectin MDAs would maximize effects against STHs. A proactive, integrated
      control platform that targets malaria and STHs would be extremely cost-effective
      and simultaneously reduce human suffering caused by multiple diseases. This paper
      outlines the benefits of adding albendazole to ivermectin MDAs for malaria
      parasite transmission suppression. 

PMID- 25070999
TI  - Use of Japanese encephalitis vaccine in US travel medicine practices in Global
      TravEpiNet.
AB  - Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical
      practice are available. We identified 711 travelers at higher risk and 7,578
      travelers at lower risk for JE who were seen at US Global TravEpiNet sites from
      September of 2009 to August of 2012. Higher-risk travelers were younger than
      lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70%
      of higher-risk travelers neither received JE vaccine during the clinic visit nor
      had been previously vaccinated. In the majority of these instances, clinicians
      determined that the JE vaccine was not indicated for the higher-risk traveler,
      which contradicts current recommendations of the Advisory Committee on
      Immunization Practices. Better understanding is needed of the clinical decision
      making regarding JE vaccine in US travel medicine practices. 

PMID- 25071000
TI  - Interleukin-6 and interleukin-10 gene promoter polymorphisms and risk of endemic
      Burkitt lymphoma.
AB  - Overexpression of interleukin-6 (IL-6) and IL-10 in endemic Burkitt lymphoma
      (eBL) may facilitate tumorigenesis by providing a permissive cytokine milieu.
      Promoter polymorphisms influence interindividual differences in cytokine
      production. We hypothesized that children genetically predisposed for elevated
      cytokine levels may be more susceptible to eBL. Using case-control samples from
      western Kenya consisting of 117 eBL cases and 88 ethnically matched healthy
      controls, we tested for the association between eBL risk and IL-10 (rs1800896,
      rs1800871, and rs1800872) and IL-6 (rs1800795) promoter single nucleotide
      polymorphisms (SNPs) as well as IL-10 promoter haplotypes. In addition, the
      association between these variants and Epstein Barr Virus (EBV) load was
      examined. Results showed that selected IL-10 and IL-6 promoter SNPs and IL-10
      promoter haplotypes were not associated with risk eBL or EBV levels in EBV
      seropositive children. Findings from this study reveal that common variants
      within the IL-10 and IL-6 promoters do not independently increase eBL risk in
      this vulnerable population. 

PMID- 25071001
TI  - Treatment outcomes for patients with multidrug-resistant tuberculosis in post
      earthquake Port-au-Prince, Haiti.
AB  - We report outcomes and 12-month survival for the first cohort of patients to
      undergo multidrug-resistant tuberculosis (MDR-TB) treatment after the earthquake
      in Haiti. From March 3, 2010 to March 28, 2013, 110 patients initiated treatment
      of laboratory-confirmed MDR-TB at the Groupe Haitien d'Etude du Sarcome de Kaposi
      et des Infections Opportunistes (GHESKIO) Center in Port-au-Prince, Haiti. Twenty
      seven patients (25%) were human immunodeficiency virus (HIV)-positive. As of
      October 31, 2013, 95 (86%) patients were either cured or alive on treatment, 4
      (4%) patients defaulted, and 11 (10%) patients died. Culture conversion occurred
      by 30 days in 14 (13%) patients, 60 days in 49 (45%) patients, and 90 days in 81
      (74%) patients. The probabilities of survival to 12 months were 96% (95%
      confidence interval [95% CI] = 89-99) and 85% (95% CI = 64-94) for HIV-negative
      and -positive patients, respectively. Despite adverse conditions, outcomes for
      patients with MDR-TB are highly encouraging. Major efforts are underway to scale
      up community directly observed therapy and expand care to other regions of Haiti.

PMID- 25071002
TI  - Campylobacter fetus bacteremia in an immunocompetent traveler.
AB  - Campylobacter fetus bacteremia is a rare human infection that occurs almost
      exclusively in the setting of advanced age, immunosuppression, human
      immunodeficiency virus infection, alcoholism, or recent gastrointestinal surgery.
      This report of C. fetus bacteremia in a 39-year-old immunocompetent traveler who
      ate raw beef identifies C. fetus as a potential emerging pathogen in normal
      hosts. 

PMID- 25071003
TI  - Comparison of quantitative and qualitative tests for glucose-6-phosphate
      dehydrogenase deficiency.
AB  - A barrier to eliminating Plasmodium vivax malaria is inadequate treatment of
      infected patients. 8-Aminoquinoline-based drugs clear the parasite; however,
      people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk for
      hemolysis from these drugs. Understanding the performance of G6PD deficiency
      tests is critical for patient safety. Two quantitative assays and two qualitative
      tests were evaluated. The comparison of quantitative assays gave a Pearson
      correlation coefficient of 0.7585 with significant difference in mean G6PD
      activity, highlighting the need to adhere to a single reference assay. Both
      qualitative tests had high sensitivity and negative predictive value at a cutoff
      G6PD value of 40% of normal activity if interpreted conservatively and performed
      under laboratory conditions. The performance of both tests dropped at a cutoff
      level of 45%. Cytochemical staining of specimens confirmed that heterozygous
      females with > 50% G6PD-deficient cells can seem normal by phenotypic tests. 

PMID- 25071004
TI  - Delayed anemia after treatment with injectable artesunate in the Democratic
      Republic of the Congo: a manageable issue.
AB  - Cases of delayed hemolytic anemia have been described after treatment with
      injectable artesunate, the current World Health Organization (WHO)-recommended
      first-line drug for the treatment of severe malaria. A total of 350 patients (215
      [61.4%] < 5 years of age and 135 [38.6%] >= 5 years of age) were followed-up
      after treatment with injectable artesunate for severe malaria in hospitals and
      health centers of the Democratic Republic of the Congo. Complete series of
      hemoglobin (Hb) measurements were available for 201 patients. A decrease in Hb
      levels between 2 and 5 g/dL was detected in 23 (11.4%) patients during the follow
      up period. For five patients, Hb levels decreased below 5 g/dL during at least
      one follow-up visit. All cases of delayed anemia were clinically manageable and
      resolved within one month. 

PMID- 25071005
TI  - Water-related infrastructure in a region of post-earthquake Haiti: high levels of
      fecal contamination and need for ongoing monitoring.
AB  - We inventoried non-surface water sources in the Leogane and Gressier region of
      Haiti (approximately 270 km(2)) in 2012 and 2013 and screened water from 345
      sites for fecal coliforms and Vibrio cholerae. An international organization/non
      governmental organization responsible for construction could be identified for
      only 56% of water points evaluated. Sixteen percent of water points were non
      functional at any given time; 37% had evidence of fecal contamination, with
      spatial clustering of contaminated sites. Among improved water sources (76% of
      sites), 24.6% had fecal coliforms versus 80.9% in unimproved sources. Fecal
      contamination levels increased significantly from 36% to 51% immediately after
      the passage of Tropical Storm Sandy in October of 2012, with a return to 34%
      contamination in March of 2013. Long-term sustainability of potable water
      delivery at a regional scale requires ongoing assessment of water quality,
      functionality, and development of community-based management schemes supported by
      a national plan for the management of potable water. 

PMID- 25071006
TI  - FANCD2 re-expression is associated with glioma grade and chemical inhibition of
      the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents.
AB  - Brain tumours kill more children and adults under 40 than any other cancer.
      Around half of primary brain tumours are glioblastoma multiforme (GBMs) where
      treatment remains a significant challenge, where survival rates have improved
      little over the last 40 years, thus highlighting an unmet need for the
      identification/development of novel therapeutic targets and agents to improve GBM
      treatment. Using archived and fresh glioma tissue, we show that in contrast to
      normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key
      protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA
      pathway. Importantly, FANCD2 expression levels are strongly associated with
      tumour grade, revealing a potential exploitable therapeutic window to allow
      inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue.
      Using several small molecule inhibitors of the FA pathway in combination with
      isogenic FA-proficient/deficient glioma cell lines as well as primary GBM
      cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to
      the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore
      provide a strong rationale for the development of novel and potent inhibitors of
      the FA pathway to improve the treatment of GBMs, which may ultimately impact on
      patient outcome. 

PMID- 25071007
TI  - MicroRNA-99a and 100 mediated upregulation of FOXA1 in bladder cancer.
AB  - Urothelial cell carcinoma of the bladder (UCC) is a common disease often
      characterized by FGFR3 dysregulation. Whilst upregulation of this oncogene occurs
      most frequently in low-grade non-invasive tumors, recent data reveal increased
      FGFR3 expression characterizes a common sub-type of invasive UCC sharing
      molecular similarities with breast cancer. These similarities include
      upregulation of the FOXA1 transcription factor and reduced expression of
      microRNAs-99a/100. We have previously identified direct regulation of FGFR3 by
      these two microRNAs and now search for further targets. Using a microarray meta
      database we find potential FOXA1 regulation by microRNAs-99a/100. We confirm
      direct targeting of the FOXA1 3'UTR by microRNAs-99a/100 and also potential
      indirect regulation through microRNA-485-5p/SOX5/JUN-D/FOXL1 and microRNA
      486/FOXO1a. In 292 benign and malignant urothelial samples, we find an inverse
      correlation between the expression of FOXA1 and microRNAs-99a/100 (r=-0.33 to 
      0.43, p<0.05). As for FGFR3 in UCC, tumors with high FOXA1 expression have lower
      rates of progression than those with low expression (Log rank p=0.009). Using
      global gene expression and CpG methylation profiling we find genotypic
      consequences of FOXA1 upregulation in UCC. Genetic changes are associated with
      regional hypomethylation, occur near FOXA1 binding sites, and mirror gene
      expression changes previously reported in FGFR3 mutant-UCC. These include gene
      silencing through aberrant hypermethylation (e.g. IGFBP3) and affect genes
      characterizing breast cancer sub-types (e.g. ERBB2). In conclusion, we have
      identified microRNAs-99a/100 mediate a direct relationship between FGFR3 and
      FOXA1 and potentially facilitate cross talk between these pathways in UCC. 

PMID- 25071008
TI  - Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
AB  - The correlation between DNA methylation and a subset of histone post
      translational modifications (positive and negative) has hinted at an underlying
      regulatory crosstalk between histone marks and DNA methylation in patterning the
      human DNA methylome, an idea further supported by corresponding alterations to
      both histone marks and DNA methylation during malignant transformation. This
      study investigated the framework by which histone marks influence DNA methylation
      at a genome-wide level. Using RNAi in a pluripotent human embryonic carcinoma
      cell line we depleted essential components of the MLL/COMPASS, polycomb
      repressive complex 2 (PRC2), and PRC1 histone modifying complexes that establish,
      respectively, the post-translational modifications H3K4me3, H3K27me3, and
      H2AK119ub, and assayed the impact of the subsequent depletion of these marks on
      the DNA methylome. Absence of H2AK119ub resulted predominantly in hypomethylation
      across the genome. Depletion of H3K4me3 and, surprisingly, H3K27me3 caused CpG
      island hypermethylation at a subset of loci. Intriguingly, many promoters were co
      regulated by all three histone marks, becoming hypermethylated with loss of
      H3K4me3 or H3K27me3 and hypomethylated with depletion of H2AK119ub, and many of
      these co-regulated loci were among those commonly targeted for aberrant
      hypermethylation in cancer. Taken together, our results elucidate novel roles for
      polycomb and MLL/COMPASS in regulating DNA methylation and define targets of this
      regulation. 

PMID- 25071009
TI  - The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting
      of inhibitors of apoptosis.
AB  - Treatment resistance, the major challenge in the management of advanced prostate
      cancer, is in part based on resistance to apoptosis. The Inhibitor of Apoptosis
      (IAP) family is thought to play key roles in survival and drug resistance of
      cancer via inhibition of apoptosis. Of the IAP family members, cIAP1, cIAP2, XIAP
      and survivin are known to be up-regulated in prostate cancer. BIRC6, a much less
      studied IAP member, was recently shown to be elevated in castration-resistant
      prostate cancer (CRPC). In the present study, we showed a correlation between
      elevated BIRC6 expression in clinical prostate cancer specimens and poor patient
      prognostic factors, as well as co-upregulation of certain IAP members. In view of
      this, we designed antisense oligonucleotides that simultaneously target BIRC6 and
      another co-upregulated IAP member (dASOs). Two dASOs, targeting BIRC6+cIAP1 and
      BIRC6+survivin, showed substantial inhibition of CRPC cells proliferation,
      exceeding that obtained with single BIRC6 targeting. The growth inhibition was
      associated with increased apoptosis, cell cycle arrest and suppression of NFkB
      activation. Moreover, treatment with both dASOs led to significantly lower viable
      tumor volume in vivo, without major host toxicity. This study shows that BIRC6
      based dual IAP-targeting ASOs represent potential novel therapeutic agents
      against advanced prostate cancer. 

PMID- 25071010
TI  - Transcriptional regulation of the p73 gene by Nrf-2 and promoter CpG methylation
      in human breast cancer.
AB  - To understand the transcriptional regulation of p73 by promoter methylation and
      Nrf-2 in breast carcinogenesis, ChIP assay indicated that Nrf-2 can bind to both
      promoters and can activate the transcription of TAp73 and DeltaNp73 in MCF-7 cell
      line, knockdown of Nrf-2 gene resulted in an abrogation of TAp73 and DeltaNp73
      expression in the cells transfected with sh-Nrf-2 as well as Nrf-2 knock out
      mouse model. However, we found Nrf-2 induced DeltaNp73 expression was abolished
      with 5-aza-dC treatment, thus lead to a down-regulated DeltaNp73 and an up
      regulated TAp73 expression in breast cancer cells lines. Consistent with this
      model, we detected decreased TAp73 and increased DeltaNp73 expression in breast
      cancer tissue, along with increased TAp73 but decreased DeltaNp73 expression in
      corresponding surrounding noncancerous tissues (NCTs) in a breast cancer tissue
      assay. A significant inverse correlation was found between TAp73 and DeltaNp73
      expression in the above tissue-array (P = 0.047) and validated in another set
      consisting of 128 breast cancer tumor tissue (P = 0.034). Taken together, our
      findings suggest that Nrf-2 and promoter methylation cooperatively govern the
      transcriptional regulation of p73, and unbalanced expression of TAp73 and
      DeltaNp73 expression plays a critical role in breast cancer development. 

PMID- 25071011
TI  - Epigenetic regulations in the IFNgamma signalling pathway: IFNgamma-mediated MHC
      class I upregulation on tumour cells is associated with DNA demethylation of
      antigen-presenting machinery genes.
AB  - Downregulation of MHC class I expression on tumour cells, a common mechanism by
      which tumour cells can escape from specific immune responses, can be associated
      with coordinated silencing of antigen-presenting machinery genes. The expression
      of these genes can be restored by IFNgamma. In this study we documented
      association of DNA demethylation of selected antigen-presenting machinery genes
      located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFNgamma
      treatment with MHC class I upregulation on tumour cells in several MHC class I
      deficient murine tumour cell lines (TC-1/A9, TRAMP-C2, MK16 and MC15). Our data
      also documented higher methylation levels in these genes in TC-1/A9 cells, as
      compared to their parental MHC class I-positive TC-1 cells. IFNgamma-mediated DNA
      demethylation was relatively fast in comparison with demethylation induced by DNA
      methyltransferase inhibitor 5-azacytidine, and associated with increased histone
      H3 acetylation in the promoter regions of APM genes. Comparative transcriptome
      analysis in distinct MHC class I-deficient cell lines upon their treatment with
      either IFNgamma or epigenetic agents revealed that a set of genes, significantly
      enriched for the antigen presentation pathway, was regulated in the same manner.
      Our data demonstrate that IFNgamma acts as an epigenetic modifier when
      upregulating the expression of antigen-presenting machinery genes. 

PMID- 25071012
TI  - Hypoxia suppresses cylindromatosis (CYLD) expression to promote inflammation in
      glioblastoma: possible link to acquired resistance to anti-VEGF therapy.
AB  - Cylindromatosis (CYLD) is a tumor suppressor that regulates signaling pathways by
      acting as a deubiquitinating enzyme. CYLDdown-regulation occurred in several
      malignancies, with tumor-promoting effects. Although we found loss of CYLD
      expression in hypoxic regions of human glioblastoma multiforme (GBM), the most
      aggressive brain tumor, biological roles of CYLD in GBM remain unknown. This
      study aimed to determine the biological significance of CYLD down-regulation to
      GBM progression and therapy. CYLD mRNA transcription was dramatically down
      regulated in hypoxic GBM cells, consistent with our clinical observations of
      human GBM tissues. Hypoxia enhanced both basal and tumor necrosis factor-alpha
      induced expression of various proinflammatory cytokines, whereas CYLD
      overexpression strongly counteracted these responses. In addition, chronic anti
      angiogenic therapy with bevacizumab, an anti-vascular endothelial growth factor
      (VEGF) antibody, with enhanced hypoxia produced responses similar to these CYLD
      regulated proinflammatory responses in a xenograft mouse model. Histologically,
      CYLD clearly prevented massive immune cell infiltration surrounding necrotic
      regions, and pseudopalisades appeared in bevacizumab-treated control tumors.
      Furthermore, CYLD overexpression, which had no impact on survival by itself,
      significantly improved the prosurvival effect of bevacizumab. These data suggest
      that CYLD down-regulation is crucial for hypoxia-mediated inflammation in GBM,
      which may affect the long-term efficacy of anti-VEGF therapy. 

PMID- 25071013
TI  - Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor
      response to chemotherapy via regulation of matrix metalloproteinase 2 expression.
AB  - Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical
      outcome. Our previous work has shown that eukaryotic initiation factor 5A2
      (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was
      identified to be an independent risk factor for poor disease-specific survival
      among HCC patients. Both in vitro and in vivo assays indicated that ablation of
      endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix
      metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a
      main component of the vascular basement membrane (BM), we subsequently
      investigated the effect of EIF5A2 on tumor vasculature remodeling using
      complementary approaches, including fluorescent immunostaining, transmission
      electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken
      together, our results indicate that EIF5A2 silencing increases tumor vessel wall
      continuity, increases blood perfusion and improves tumor oxygenation.
      Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of
      HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might
      exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and
      JNK/c-Jun pathways. CONCLUSION: This study highlights an important role of EIF5A2
      in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential
      therapeutic target in the treatment of HCC.

PMID- 25071015
TI  - p53 status as effect modifier of the association between pre-treatment fasting
      glucose and breast cancer outcomes in non diabetic, HER2 positive patients
      treated with trastuzumab.
AB  - Mounting evidence supports the role of p53 in metabolic processes involved in
      breast carcinogenesis. We investigated whether p53 status affects the association
      of pre-treatment fasting glucose with treatment outcomes in 106 non diabetic,
      HER2 positive breast cancer patients treated with trastuzumab. p53 status was
      validated against gene sequencing of selected codons in 49 patients. The Kaplan
      Meier method and log rank test were used to compare survival by categories of
      fasting glucose in the overall population and separate settings. Cox models
      included age and body mass index. Direct sequencing confirmed the lack of
      mutations in 73.7% of p53 negative patients and their presence in 53.3% of p53
      positive cases. At 66 months, 88.3% of patients with glucose <= 89.0 mg/dl
      (median value) did not experiment disease progression compared with 70.0% in the
      highest category (p=0.034), with glucose being an independent predictor
      (p=0.046). Stratified analysis confirmed this association in p53 negative
      patients only (p=0.01). In the early setting, data suggested longer disease free
      survival in p53 negative patients in the lowest glucose category (p=0.053). In
      our study, p53 status acted as effect modifier of the investigated association.
      This may help differentiate target sub-groups and affect outcomes interpretation
      in similarly characterized patients. 

PMID- 25071014
TI  - AKT regulates NPM dependent ARF localization and p53mut stability in tumors.
AB  - Nucleophosmin (NPM) is known to regulate ARF subcellular localization and MDM2
      activity in response to oncogenic stress, though the precise mechanism has
      remained elusive. Here we describe how NPM and ARF associate in the nucleoplasm
      to form a MDM2 inhibitory complex. We find that oligomerization of NPM drives
      nucleolar accumulation of ARF. Moreover, the formation of NPM and ARF oligomers
      antagonizes MDM2 association with the inhibitory complex, leading to activation
      of MDM2 E3-ligase activity and targeting of p53. We find that AKT phosphorylation
      of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization
      of ARF, constitutive MDM2 inhibition and stabilization of p53. We also show that
      ARF promotes p53 mutant stability in tumors and suppresses p73 mediated p21
      expression and senescence. We demonstrate that AKT and PI3K inhibitors may be
      effective in treatment of therapeutically resistant tumors with elevated AKT and
      carrying gain of function mutations in p53. Our results show that the clinical
      candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced
      p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft
      model of pancreatic cancer. Analysis of human tumors indicates that phospho-S48
      NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of
      AKT inhibitor treatment. Critically, we propose that combination therapy
      involving PI3K-AKT inhibitors would benefit from a patient stratification
      rationale based on ARF and p53(mut) status. 

PMID- 25071016
TI  - Thyroid hormone regulates adhesion, migration and matrix metalloproteinase 9
      activity via alphavbeta3 integrin in myeloma cells.
AB  - Thyroid hormone (3,5,3'-triiodothyronine, T3; L-thyroxine, T4) enhances cancer
      cell proliferation, invasion and angiogenesis via a discrete receptor located
      near the RGD recognition site on alphavbeta3 integrin. Tetraiodothyroacetic acid
      (tetrac) and its nanoparticulate formulation interfere with binding of T3/T4 to
      the integrin. This integrin is overexpressed in multiple myeloma (MM) and other
      cancers. MM cells interact with alphavbeta3 integrin to support growth and
      invasion. Matrix metalloproteinases (MMPs) are a family of enzymes active in
      tissue remodeling and cancer. The association between integrins and MMPs
      secretion and action is well established. In the current study, we examined the
      effects of thyroid hormone on myeloma cell adhesion, migration and MMP activity.
      We show that T3 and T4 increased myeloma adhesion to fibronectin and induced
      alphavbeta3 clustering. In addition, the hormones induced MMP-9 expression and
      activation via alphavbeta3 and MAPK induction. Bortezomib, a standard myeloma
      treatment, caused a decrease in activity/quantity of MMPs and thyroid hormone
      opposed this effect. RGD peptide and tetrac impaired the production of MMP-9 in
      cell lines and in primary BM cells from myeloma patients. In conclusion, thyroid
      hormone-dependent regulation via alphavbeta3 of myeloma cell adhesion and MMP-9
      production may play a role in myeloma migration and progression. 

PMID- 25071017
TI  - Eradication of metastatic melanoma through cooperative expression of RNA-based
      HDAC1 inhibitor and p73 by oncolytic adenovirus.
AB  - Malignant melanoma is a highly aggressive cancer that retains functional p53 and
      p73, and drug unresponsiveness largely depends on defects in death pathways after
      epigenetic gene silencing in conjunction with an imbalanced p73/DNp73 ratio. We
      constructed oncolytic viruses armed with an inhibitor of deacetylation and/or p73
      to specifically target metastatic cancer. Arming of the viruses is aimed at
      lifting epigenetic blockage and re-opening apoptotic programs in a staggered
      manner enabling both, efficient virus replication and balanced destruction of
      target cells through apoptosis. Our results showed that cooperative expression of
      shHDAC1 and p73 efficiently enhances apoptosis induction and autophagy of
      infected cells which reinforces progeny production. In vitro analyses revealed
      100% cytotoxicity after infecting cells with OV.shHDAC1.p73 at a lower virus dose
      compared to control viruses. Intriguingly, OV.shHDAC1.p73 acts as a potent
      inhibitor of highly metastatic xenograft tumors in vivo. Tumor expansion was
      significantly reduced after intratumoral injection of 3 x 108 PFU of either
      OV.shHDAC1 or OV.p73 and, most important, complete regression could be achieved
      in 100 % of tumors treated with OV.shHDAC1.p73. Our results point out that the
      combination of high replication capacity and simultaneous restoration of cell
      death routes significantly enhance antitumor activity.

PMID- 25071018
TI  - SHP-1 is a target of regorafenib in colorectal cancer.
AB  - Regorafenib is an inhibitor of multiple protein kinases which exerts antitumor
      and antimetastatic activities in metastatic colorectal cancer (CRC). SH2 domain
      containing phosphatase 1 (SHP-1) is reported to have tumor suppressive potential
      because it acts as a negative regulator of p-STAT3(Tyr705) signaling. However,
      little is known about the mechanism regarding regorafenib affects SHP-1 tyrosine
      phosphatase activity and leads to apoptosis and tumor suppression in CRC. Here,
      we found that regorafenib triggered apoptotic cell death and significantly
      enhanced SHP-1 activity, which dramatically decreased the phosphorylated form of
      STAT3 at Tyr705 (p-STAT3(Tyr705)). Importantly, regorafenib augmented SHP-1
      activity by direct disruption of the association between N-SH2 and catalytic PTP
      domain of SHP-1. Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of
      SHP-1 blocked the effect of regorafenib-induced SHP-1 activity, growth inhibition
      and a decrease of p-STAT3(Tyr705) expression, suggesting that regorafenib
      triggers a conformational change in SHP-1 by relieving its autoinhibition. In
      vivo assay showed that regorafenib significantly inhibited xenograft growth and
      decreased p-STAT3(Tyr705) expression but induced higher SHP-1 activity.
      Collectively, regorafenib is a novel SHP-1 agonist exerts superior anti-tumor
      effects by enhancing SHP-1 activity that directly targets p-STAT3(Tyr705). Small
      molecule-enhancement of SHP-1 activity may be a promising therapeutic approach
      for CRC treatment. 

PMID- 25071019
TI  - Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles.
AB  - Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth
      and metastasis in mice by reversing epithelial-mesenchymal transition (EMT).
      Since EMT is known to confer drug resistance to cancer cells, we wanted to
      investigate whether anti-EMT property of AuNP could be utilized to sensitize
      ovarian cancer cells to cisplatin. Herein, we report that AuNPs prevent cisplatin
      induced acquired chemoresistance and stemness in ovarian cancer cells and
      sensitize them to cisplatin. AuNPs inhibit cisplatin induced EMT, decrease the
      side population cells and key stem cell markers such as ALDH1, CD44, CD133, Sox2,
      MDR1 and ABCG2 in ovarian cancer cells. Mechanistically, AuNPs prevent cisplatin
      induced activation of Akt and NF-kB signaling axis in ovarian cancer cells that
      are critical for EMT, stem cell maintenance and drug resistance. In vivo, AuNPs
      sensitize orthotopically implanted ovarian tumor to a low dose of cisplatin and
      significantly inhibit tumor growth via facilitated delivery of both AuNP and
      cisplatin. These findings suggest that by depleting stem cell pools and
      inhibiting key molecular pathways gold nanoparticles sensitize ovarian cancer
      cells to cisplatin and may be used in combination to inhibit tumor growth and
      metastasis in ovarian cancer. 

PMID- 25071020
TI  - Oncogene-mediated regulation of p53 ISGylation and functions.
AB  - Oncogene-mediated cellular transformation is a multistep process involving
      activation of growth-promoting pathways as well as inactivation of tumor
      suppressors. We recently found that ISGylation of the p53 tumor suppressor is an
      important novel mechanism to control its stability. Here we identified that Isg15
      dependent regulation of p53 can be enhanced by different oncogenes. We further
      show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a
      positive effect on p53 ISGylation by enhancing Herc5 binding. In turn, deletion
      of Isg15 results in accumulation and activation of native p53 in transformed
      cells thus increasing its anti-cancer activity and suppressing tumorigenesis in
      mice. We propose that Isg15-dependent degradation of p53 is an alternative
      pathway for oncogenes to regulate p53 activity, and thus is an attractive pathway
      for development of new anti-cancer drugs.

PMID- 25071021
TI  - HERG1 functions as an oncogene in pancreatic cancer and is downregulated by miR
      96.
AB  - Pancreatic cancer is an aggressive malignancy with an extremely poor prognosis.
      The human ether-a-go-go-related potassium channel (HERG1) is a human rapid
      delayed rectifier, which is involved in many crucial cellular events. In this
      article, we find that HERG1 expression is dramatically increased both in
      pancreatic cancer tissues and cell lines, and that increased HERG1 expression is
      significantly related to the development of pancreatic cancer. HERG1 silencing in
      pancreatic cancer-derived cell lines PANC-1 and CFPAC-1 strongly inhibits their
      malignant capacity in vitro as well as tumorigenicity and metastasis in nude
      mice. In addition, HERG1 is identified as a direct target of miR-96, which is
      downregulated in pancreatic cancer tissues and cell lines. Ectopic expression of
      miR-96 represses the HERG1 expression in pancreatic cancer and significantly
      inhibits malignant behavior of pancreatic cancer cells in vitro and in vivo.
      Collectively, our findings suggest that miR-96 acts as a tumor suppressor in
      pancreatic cancer and may therefore serve as a useful therapeutic target for the
      development of new anticancer therapy.

PMID- 25071022
TI  - FAS/FASL are dysregulated in chordoma and their loss-of-function impairs
      zebrafish notochord formation.
AB  - Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and
      is thought to derive from notochord remnants not correctly regressed during
      development. Apoptosis is necessary for the proper notochord development in
      vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been
      demonstrated to be involved in notochord cells regression. This study was
      conducted to investigate the expression of FAS/FASL pathway in a cohort of skull
      base chordomas and to analyze the role of fas/fasl homologs in zebrafish
      notochord formation. FAS/FASL expression was found to be dysregulated in chordoma
      leading to inactivation of the downstream Caspases in the samples analyzed. Both
      fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas
      and fasl loss-of-function mainly resulted in larvae with notochord multi-cell
      layer jumps organization, larger vacuolated notochord cells, defects in the peri
      notochordal sheath structure and in vertebral mineralization. Interestingly, we
      observed the persistent expression of ntla and col2a1a, the zebrafish homologs of
      the human T gene and COL2A1 respectively, which are specifically up-regulated in
      chordoma. These results demonstrate for the first time the dysregulation of
      FAS/FASL in chordoma and their role in notochord formation in the zebrafish
      model, suggesting their possible implication in chordoma onset.

PMID- 25071023
TI  - GLP-1 receptor activation modulates appetite- and reward-related brain areas in
      humans.
AB  - Gut-derived hormones, such as GLP-1, have been proposed to relay information to
      the brain to regulate appetite. GLP-1 receptor agonists, currently used for the
      treatment of type 2 diabetes (T2DM), improve glycemic control and stimulate
      satiety, leading to decreases in food intake and body weight. We hypothesized
      that food intake reduction after GLP-1 receptor activation is mediated through
      appetite- and reward-related brain areas. Obese T2DM patients and normoglycemic
      obese and lean individuals (n = 48) were studied in a randomized, crossover,
      placebo-controlled trial. Using functional MRI, we determined the acute effects
      of intravenous administration of the GLP-1 receptor agonist exenatide, with or
      without prior GLP-1 receptor blockade using exendin 9-39, on brain responses to
      food pictures during a somatostatin pancreatic-pituitary clamp. Obese T2DM
      patients and normoglycemic obese versus lean subjects showed increased brain
      responses to food pictures in appetite- and reward-related brain regions (insula
      and amygdala). Exenatide versus placebo decreased food intake and food-related
      brain responses in T2DM patients and obese subjects (in insula, amygdala,
      putamen, and orbitofrontal cortex). These effects were largely blocked by prior
      GLP-1 receptor blockade using exendin 9-39. Our findings provide novel insights
      into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor
      agonists cause weight loss.

PMID- 25071024
TI  - Impaired adiponectin signaling contributes to disturbed catabolism of branched
      chain amino acids in diabetic mice.
AB  - The branched-chain amino acids (BCAA) accumulated in type 2 diabetes are
      independent contributors to insulin resistance. The activity of branched-chain
      alpha-keto acid dehydrogenase (BCKD) complex, rate-limiting enzyme in BCAA
      catabolism, is reduced in diabetic states, which contributes to elevated BCAA
      concentrations. However, the mechanisms underlying decreased BCKD activity remain
      poorly understood. Here, we demonstrate that mitochondrial phosphatase 2C
      (PP2Cm), a newly identified BCKD phosphatase that increases BCKD activity, was
      significantly downregulated in ob/ob and type 2 diabetic mice. Interestingly, in
      adiponectin (APN) knockout (APN(-/-)) mice fed with a high-fat diet (HD), PP2Cm
      expression and BCKD activity were significantly decreased, whereas BCKD kinase
      (BDK), which inhibits BCKD activity, was markedly increased. Concurrently, plasma
      BCAA and branched-chain alpha-keto acids (BCKA) were significantly elevated. APN
      treatment markedly reverted PP2Cm, BDK, BCKD activity, and BCAA and BCKA levels
      in HD-fed APN(-/-) and diabetic animals. Additionally, increased BCKD activity
      caused by APN administration was partially but significantly inhibited in PP2Cm
      knockout mice. Finally, APN-mediated upregulation of PP2Cm expression and BCKD
      activity were abolished when AMPK was inhibited. Collectively, we have provided
      the first direct evidence that APN is a novel regulator of PP2Cm and systematic
      BCAA levels, suggesting that targeting APN may be a pharmacological approach to
      ameliorating BCAA catabolism in the diabetic state.

PMID- 25071025
TI  - Compartmentalized acyl-CoA metabolism in skeletal muscle regulates systemic
      glucose homeostasis.
AB  - The impaired capacity of skeletal muscle to switch between the oxidation of fatty
      acid (FA) and glucose is linked to disordered metabolic homeostasis. To
      understand how muscle FA oxidation affects systemic glucose, we studied mice with
      a skeletal muscle-specific deficiency of long-chain acyl-CoA synthetase (ACSL)1.
      ACSL1 deficiency caused a 91% loss of ACSL-specific activity and a 60-85%
      decrease in muscle FA oxidation. Acsl1(M-/-) mice were more insulin sensitive,
      and, during an overnight fast, their respiratory exchange ratio was higher,
      indicating greater glucose use. During endurance exercise, Acsl1(M-/-) mice ran
      only 48% as far as controls. At the time that Acsl1(M-/-) mice were exhausted but
      control mice continued to run, liver and muscle glycogen and triacylglycerol
      stores were similar in both genotypes; however, plasma glucose concentrations in
      Acsl1(M-/-) mice were ~40 mg/dL, whereas glucose concentrations in controls were
      ~90 mg/dL. Excess use of glucose and the likely use of amino acids for fuel
      within muscle depleted glucose reserves and diminished substrate availability for
      hepatic gluconeogenesis. Surprisingly, the content of muscle acyl-CoA at
      exhaustion was markedly elevated, indicating that acyl-CoAs synthesized by other
      ACSL isoforms were not available for beta-oxidation. This compartmentalization of
      acyl-CoAs resulted in both an excessive glucose requirement and severely
      compromised systemic glucose homeostasis.

PMID- 25071026
TI  - Adiponectin stimulates autophagy and reduces oxidative stress to enhance insulin
      sensitivity during high-fat diet feeding in mice.
AB  - Numerous studies have characterized the antidiabetic effects of adiponectin, yet
      the precise cellular mechanisms in skeletal muscle, in particular, changes in
      autophagy, require further clarification. In the current study, we used a high
      fat diet (HFD) to induce obesity and insulin resistance in wild-type (WT) or
      adiponectin knockout (Ad-KO) mice with and without adiponectin replenishment.
      Temporal analysis of glucose tolerance and insulin sensitivity using
      hyperinsulinemic-euglycemic clamp and muscle insulin receptor substrate and Akt
      phosphorylation demonstrated exaggerated and more rapid HFD-induced insulin
      resistance in skeletal muscle of Ad-KO mice. Superoxide dismutase activity, the
      reduced glutathione-to-glutathione disulfide ratio, and lipid peroxidation
      indicated that HFD-induced oxidative stress was corrected by adiponectin. Gene
      array analysis implicated several antioxidant enzymes, including Gpxs, Prdx, Sod,
      and Nox4, in mediating this effect. Adiponectin also attenuated palmitate-induced
      reactive oxygen species production in cultured myotubes and improved insulin
      stimulated glucose uptake in primary muscle cells. Increased LC3-II and decreased
      p62 expression suggested that HFD induced autophagy in muscle of WT mice;
      however, these changes were not observed in Ad-KO mice. Replenishing adiponectin
      in Ad-KO mice increased LC3-II and Beclin1 and decreased p62 protein levels,
      induced fibroblast growth factor-21 expression, and corrected HFD-induced
      decreases in LC3, Beclin1, and ULK1 gene expression. In vitro studies examining
      changes in phospho-ULK1 (Ser555), LC3-II, and lysosomal enzyme activity confirmed
      that adiponectin directly induced autophagic flux in cultured muscle cells in an
      AMPK-dependent manner. We overexpressed an inactive mutant of Atg5 to create an
      autophagy-deficient cell model, and together with pharmacological inhibition of
      autophagy, demonstrated reduced insulin sensitivity under these conditions. In
      summary, adiponectin stimulated skeletal muscle autophagy and antioxidant
      potential to reduce insulin resistance caused by HFD.

PMID- 25071027
TI  - Metformin supports the antidiabetic effect of a sodium glucose cotransporter 2
      inhibitor by suppressing endogenous glucose production in diabetic mice.
AB  - Combined use of metformin and a sodium glucose cotransporter 2 inhibitor (SGLT2I)
      is a promising treatment strategy for type 2 diabetes. The mechanism by which
      combination treatment provides better glycemic control than metformin or SGLT2I
      monotherapy remains elusive. Therefore, we investigated the physiological
      mechanism by which both compounds lower blood glucose concentrations in diabetic
      mice. We compared the potential of metformin and the SGLT2I AVE2268 alone or in
      combination to mitigate hyperglycemia and modulate glucose fluxes in db/db and
      diabetic Tallyho/JngJ mice. SGLT2I treatment alone elicited a rapid decline in
      circulating blood glucose levels, which appeared to induce endogenous glucose
      production. Supplementation of metformin dampened this counterresponse, and
      therefore, combination therapy more efficiently maintained glycemic control.
      Finally, combination treatment blunted postprandial glucose excursions and
      improved HbA1c levels within 2 weeks. We conclude that coapplication of metformin
      enhances the glucose-lowering actions of SGLT2I by restraining endogenous glucose
      production, which may provide long-term improvement of glycemic control in type 2
      diabetic patients.

PMID- 25071028
TI  - Old battles.

PMID- 25071029
TI  - Skin diseases in primary care: what should GPs be doing?

PMID- 25071030
TI  - Diagnosis of coeliac disease in children in primary care and clinical
      implications.

PMID- 25071031
TI  - Bariatric surgery: implications for primary care.

PMID- 25071032
TI  - Diabetes and depression in general practice: meeting the challenge of managing
      comorbidity.

PMID- 25071034
TI  - Effect of Ramadan fasting on emergency walk-in-clinics in Jordan.

PMID- 25071035
TI  - Access, continuity, or both.

PMID- 25071036
TI  - Access to general practice and A&E attendance.

PMID- 25071037
TI  - Patients are often unaware of how to access medical help out of hours.

PMID- 25071038
TI  - A simple clinical coding strategy to improve recording of child maltreatment
      concerns: an audit study.

PMID- 25071039
TI  - How can we communicate better with social services?

PMID- 25071040
TI  - 'Good diabetes care' and the NDA.

PMID- 25071041
TI  - Manchester IRIS Project Service Review.

PMID- 25071043
TI  - Parkrun eases the loneliness of the long-distance runner.

PMID- 25071044
TI  - The GP as an investigator.

PMID- 25071045
TI  - Sir Michael Drury: an appreciation.

PMID- 25071046
TI  - Obesity, pelvic inflammatory disease, falls prevention, and domestic violence.

PMID- 25071047
TI  - GPs: Behind Closed Doors: practice reflections on appearing on national TV.

PMID- 25071048
TI  - Tragedy - a walk on the wild side.

PMID- 25071052
TI  - The strange time-bending properties of the appointment book.

PMID- 25071053
TI  - Raising the issue of overweight and obesity with the South Asian community.

PMID- 25071054
TI  - Resisting the tick box culture: refocusing medical education and training.

PMID- 25071055
TI  - Diagnosis and management of psoriatic arthropathy in primary care.

PMID- 25071056
TI  - Don't miss shiitake dermatitis: a case report.

PMID- 25071057
TI  - Research into practice: prompt diagnosis of cancer in primary care.

PMID- 25071058
TI  - Skin cancer excision performance in Scottish primary and secondary care: a
      retrospective analysis.
AB  - BACKGROUND: In contrast with most published evidence, studies from north-east
      Scotland suggest that GPs may be as good at treating skin cancers in primary care
      as secondary care specialists. AIM: To compare the quality of skin cancer
      excisions of GPs and secondary care skin specialists in east and south-east
      Scotland. DESIGN AND SETTING: A retrospective analysis of reports from GPs in
      Lothian, Fife, and Tayside regions. METHOD: Skin cancer histopathology reports
      from GPs in Lothian, Fife, and Tayside regions in 2010 were compared with reports
      from skin specialists in November 2010. The histopathology reports were rated for
      completeness and adequacy of excision. RESULTS: A total of 944 histopathology
      reports were analysed. In 1 year, GPs biopsied or excised 380 skin cancers. In 1
      month, dermatologists biopsied or excised 385 skin cancers, and plastic surgeons
      179 skin cancers. 'High risk' basal cell carcinomas (BCC) comprised 63.0% of BCC
      excised by GPs. For all skin cancer types, GPs excised smaller lesions, and had a
      lower rate of complete excisions compared with skin specialists. A statistical
      difference was demonstrated for BCC excisions only. CONCLUSION: GPs in east and
      south-east Scotland excise a number of skin cancers including malignant melanoma
      (MM), squamous cell carcinoma (SCC) and high-risk BCC. Despite removing smaller
      lesions, less commonly on difficult surgical sites of the head and neck, GP
      excision rates are lower for all skin cancers, and statistically inferior for
      BCC, compared with secondary care, supporting the development of guidelines in
      Scotland similar to those in other UK regions. Poorer GP excision rates may have
      serious consequences for patients with high-risk lesions.

PMID- 25071059
TI  - Development and validation of the Molluscum Contagiosum Diagnostic Tool for
      Parents: diagnostic accuracy study in primary care.
AB  - BACKGROUND: Molluscum contagiosum (MC) is diagnosed by its distinct appearance.
      Parental diagnosis of MC may reduce anxiety and lead to reductions in healthcare
      consultations, and may be particularly useful in large-scale epidemiological
      studies. However, there are currently no published, validated tools allowing
      parental diagnosis of MC. AIM: To develop and validate a tool for parental
      diagnosis of MC. DESIGN AND SETTING: The Molluscum Contagiosum Diagnostic Tool
      for Parents (MCDTP) was developed and its diagnostic accuracy was compared with
      GP diagnosis in 12 GP surgeries in South Wales. METHOD: Following development,
      which involved three phases with dermatologists, nurses, GPs, and parents,
      parents completed the MCDTP (index test) in the practice waiting room, and rated
      their confidence in their diagnosis. A GP then examined their child for MC
      (reference test). Test characteristics were calculated for all responders and for
      those who expressed being confident or very confident in their diagnosis.
      RESULTS: A total of 203 parents completed the MCDTP. The MCDTP showed a
      sensitivity of 91.5% (95% confidence intervals (CI) = 81.3 to 97.2) and a
      specificity of 88.2% (95% CI = 81.8 to 93.0) in all parents and a sensitivity of
      95.8% (95% CI = 85.7 to 99.5) and a specificity of 90.9% (95% CI = 83.9 to 95.6)
      in parents who were confident or very confident in their diagnosis. The positive
      predictive value was 76.1% (95% CI = 64.5 to 85.4) and negative predictive value
      was 96.2% (95% CI = 91.4 to 98.8) for all parents. CONCLUSION: The MCDTP
      performed well compared with GP diagnosis and is suitable for clinical use by
      parents and in population-based studies.

PMID- 25071060
TI  - Recognising Kawasaki disease in UK primary care: a descriptive study using the
      Clinical Practice Research Datalink.
AB  - BACKGROUND: Kawasaki disease is a rare childhood illness that can present non
      specifically, making it a diagnostic challenge. The clinical presentation of
      Kawasaki disease has not been previously described in primary care. AIM: To
      describe how children with an eventual diagnosis of Kawasaki disease initially
      present to primary care in the UK. DESIGN AND SETTING: The Clinical Practice
      Research Datalink was used to find cases coded as Kawasaki disease. Hospital
      Episode Statistics, hospital admissions, and hospital outpatient attendances were
      used to identify the children with a convincing diagnosis of Kawasaki disease.
      METHOD: Questionnaires and a request for copies of relevant hospital summaries,
      discharge letters, and reports were sent to GPs of the 104 children with a
      diagnosis of Kawasaki disease between 2007 and 2011. RESULTS: Most children
      presented with few clinical features typical of Kawasaki disease. Of those with
      just one feature, a fever or a polymorphous rash were the most common. By the
      time that most children were admitted to hospital they had a more recognisable
      syndrome, with three or more clinical features diagnostic of Kawasaki disease.
      Most GPs did not consider Kawasaki disease among their differential diagnoses,
      but some GPs did suspect that the child's illness was unusual. CONCLUSION: The
      study highlighted the difficulty of early diagnosis, with most children having a
      non-specific presentation to primary care. GPs are encouraged to implement good
      safety netting, and to keep Kawasaki disease in mind when children present with
      fever and rashes.

PMID- 25071061
TI  - Influence of primary care practices on patients' uptake of diabetic retinopathy
      screening: a qualitative case study.
AB  - BACKGROUND: The NHS Diabetic Eye Screening Programme aims to reduce the risk of
      sight loss among people with diabetes in England by enabling prompt diagnosis of
      sight-threatening retinopathy. However, the rate of screening uptake between
      practices can vary from 55% to 95%. Existing research focuses on the impact of
      patient demographics but little is known about GP practice-related factors that
      can make a difference. AIM: To identify factors contributing to high or low
      patient uptake of retinopathy screening. DESIGN AND SETTING: Qualitative case
      based study; nine purposively selected GP practices (deprived/affluent; high/low
      screening uptake) in three retinopathy screening programme areas. METHODS: Semi
      structured interviews were conducted with patients, primary care professionals,
      and screeners. A comparative case-based analysis was carried out to identify
      factors related to high or low screening uptake. RESULTS: Eight possible factors
      that influenced uptake were identified. Five modifiable factors related to
      service and staff interactions: communication with screening services; contacting
      patients; integration of screening with other care; focus on the newly diagnosed;
      and perception of non-attenders. Three factors were non-modifiable challenges
      related to practice location: level of deprivation; diversity of ethnicities and
      languages; and transport and access. All practices adopted strategies to improve
      uptake, but the presence of two or more major barriers made it very hard for
      practices to achieve higher uptake levels. CONCLUSIONS: A range of service-level
      opportunities to improve screening attendance were identified that are available
      to practices and screening teams. More research is needed into the complex
      interfaces of care that make up retinopathy screening.

PMID- 25071062
TI  - Cost effectiveness of a web-based decision aid for parents deciding about MMR
      vaccination: a three-arm cluster randomised controlled trial in primary care.
AB  - BACKGROUND: Levels of measles in England and Wales are at their highest for 18
      years, and strategies targeting the different groups of parents who do not
      vaccinate their children continue to be needed. Decision aids for decisions
      regarding childhood immunisation appear to be effective in achieving an increase
      in vaccine uptake but their cost effectiveness is unknown. AIM: To assess the
      cost effectiveness of a web-based decision aid to increase uptake of the MMR
      vaccine. DESIGN AND SETTING: Economic evaluation conducted alongside a cluster
      randomised controlled trial using urban GP practices in the north of England.
      METHOD: Fifty GP practices in the north of England were randomised to one of
      three trial arms: decision aid, leaflet, usual practice. A total of 220 first
      time parents (child aged 3-12 months) were recruited. Parents self-reported their
      contacts with the NHS and other previous/expected resource utilisation;
      associated costs were calculated. Vaccine-uptake data were collected from GP
      practices. A cost-effectiveness analysis was undertaken and provided the
      incremental cost per first-vaccine uptake. Multiple imputation was used to
      account for missing data and findings were adjusted for baseline differences in
      parents' levels of decisional conflict regarding MMR vaccination. RESULTS: Of the
      220 first-time parents recruited to the study, 179 completed the baseline and
      post-intervention questionnaires. MMR uptake was highest for those receiving the
      decision aid (42 out of 42, 100%) versus usual practice (61 out of 62, 98%) and
      leaflet arm (69 out of 75, 92%), and was associated with lower cost (-L9.20
      versus usual practice and -L7.17 versus leaflet). CONCLUSION: The decision aid
      has a high chance of being cost effective, regardless of the value placed on
      obtaining additional vaccinations. It also appears to offer an efficient means of
      decision support for parents.

PMID- 25071064
TI  - Critical items for assessing risk of lung and colorectal cancer in primary care:
      a Delphi study.
AB  - BACKGROUND: Patients with lung or colorectal cancer often present late and have a
      poor prognosis. Identifying diagnostic indicators to optimally assess the risk of
      these cancers in primary care would support early identification and timely
      referral for patients at increased risk. AIM: To obtain consensus regarding
      potential diagnostic indicators that are important for assessing the risk of lung
      or colorectal cancer in primary care consulters presenting with lung or abdominal
      symptoms. DESIGN AND SETTING: A Delphi study was conducted with 28 participants
      from primary and secondary care and academic settings in the UK and Europe.
      METHOD: Indicators were obtained from systematic reviews, recent primary studies
      and consultation with experts prior to the Delphi study being conducted. Over
      three rounds, participants rated each diagnostic indicator in terms of its
      importance, ranked them in order of importance, and rated each item as crucial or
      not crucial to assess during a GP consultation. RESULTS: The final round resulted
      in 25 items remaining for each type of cancer, including established cancer
      symptoms such as rectal bleeding for colorectal cancer and haemoptysis for lung
      cancer, but also less frequently used indicators such as patients' concerns about
      cancer. CONCLUSION: This study highlights the items clinicians feel would be most
      crucial to include in the clinical assessment of primary care patients, a number
      of which have rarely been noted in the previous literature. Their importance in
      assessing the risk of lung or colorectal cancer will be tested as part of a large
      prospective cohort study (CANDID).

PMID- 25071063
TI  - Patients' experiences of using a smartphone application to increase physical
      activity: the SMART MOVE qualitative study in primary care.
AB  - BACKGROUND: Regular physical activity is known to help prevent and treat numerous
      non-communicable diseases. Smartphone applications (apps) have been shown to
      increase physical activity in primary care but little is known regarding the
      views of patients using such technology or how such technology may change
      behaviour. AIM: To explore patients' views and experiences of using smartphones
      to promote physical activity in primary care. DESIGN AND SETTING: This
      qualitative study was embedded within the SMART MOVE randomised controlled trial,
      which used an app (Accupedo-Pro Pedometer) to promote physical activity in three
      primary care centres in the west of Ireland. METHOD: Taped and transcribed semi
      structured interviews with a purposeful sample of 12 participants formed the
      basis of the investigation. Framework analysis was used to analyse the data.
      RESULTS: Four themes emerged from the analysis: transforming relationships with
      exercise; persuasive technology tools; usability; and the cascade effect. The app
      appeared to facilitate a sequential and synergistic process of positive change,
      which occurred in the relationship between the participants and their exercise
      behaviour; the study has termed this the 'Know-Check-Move' effect. Usability
      challenges included increased battery consumption and adjusting to carrying the
      smartphone on their person. There was also evidence of a cascade effect involving
      the families and communities of participants. CONCLUSION: Notwithstanding
      technological challenges, an app has the potential to positively transform, in a
      unique way, participants' relationships with exercise. Such interventions can
      also have an associated cascade effect within their wider families and
      communities.

PMID- 25071065
TI  - The impact of NHS Health Checks on the prevalence of disease in general
      practices: a controlled study.
AB  - BACKGROUND: NHS Health Checks is a national case-finding and vascular risk
      assessment programme in England. No research has been published to assess the
      impact of NHS Health Checks on the prevalence of chronic disease in GP practices.
      AIM: To examine the impact of NHS Health Checks on the prevalence of
      hypertension, coronary heart disease (CHD), chronic kidney disease (CKD), atrial
      fibrillation (AF), and diabetes within practices, and compare this with usual
      medical care. DESIGN AND SETTING: A non-randomised controlled study in a mixed
      rural and urban county in England. METHOD: Thirty-eight GP practices provided NHS
      Health Checks over a 3-year period. Forty-one practices that did not provide
      Health Checks acted as controls. t-tests and multiple linear regression were used
      to assess the difference in prevalence of disease between intervention group and
      control group practices, and the impact of NHS Health Checks on this. RESULTS:
      Throughout the duration of the study, 1142 previously undiagnosed cases of
      disease were detected through a total of 16 669 NHS Health Checks. Despite this,
      there were no significant differences in the change to the prevalence of
      diabetes, hypertension, CHD, CKD, and AF in practices providing NHS Health Checks
      compared with control practices. Regression analysis did not demonstrate that
      there was any significant association between the proportion of the eligible
      population of a practice having completed NHS Health Checks and changes in the
      prevalence of the five conditions studied. CONCLUSION: In practices providing NHS
      Health Checks, the change in the reported prevalence of diabetes, hypertension,
      CHD, CKD, and AF did not differ from that of practices providing usual care.

PMID- 25071066
TI  - Self-management for COPD?: why does it generate negative connotations?

PMID- 25071067
TI  - Predictive factors of palliative radiotherapy response and survival in patients
      with spinal metastases from hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Spinal metastases often severely limit the quality of life by
      causing severe pain and neurological deficits. The purpose of this study was to
      evaluate the palliative effect of radiotherapy (RT) for spinal metastases from
      hepatocellular carcinoma (HCC) and to identify factors predictive of survival in
      HCC patients with spinal metastases who received RT. METHODS: A retrospective
      analysis was performed on 192 patients with spinal metastases from HCC who
      received RT. RESULTS: Of 192 patients with spinal metastases from HCC, an overall
      pain response to palliative RT occurred in 187 patients (97.4%), with a complete
      pain response (CR) in 41 patients (21.4%) and a partial response in 151 patients
      (78.6%). A higher biologically effective dose (BED) and more advanced RT
      techniques were identified as predictive factors for a CR. The 1- and 2-year
      overall survival (OS) rates were 18.1% and 6.3%, respectively, and the median
      survival time was 4.5 months. A long OS was associated with good performance
      status, controlled primary HCC, absence of extrahepatic metastases, and a higher
      BED. CONCLUSIONS: RT provided effective palliation for patients with painful
      spinal metastases from HCC. Our results provide information regarding pain
      control, survival outcomes, and predictive factors for the prognosis of HCC
      patients with spinal metastases treated with RT.

PMID- 25071068
TI  - Efficacy of 7-Day and 14-Day Bismuth-Containing Quadruple Therapy and 7-Day and
      14-Day Moxifloxacin-Based Triple Therapy as Second-Line Eradication for
      Helicobacter pylori Infection.
AB  - BACKGROUND/AIMS: Bismuth-containing quadruple and moxifloxacin-based triple
      regimens are recommended as second-line therapy for Helicobacter pylori
      infection. The aim of this study was to compare the efficacy of each regimen.
      METHODS: From August 2004 to October 2012, a total of 949 patients (mean age,
      54.32+/-12.08 years; male, 49.4%) who failed H. pylori eradication with a
      standard triple regimen were included. Patients treated with a bismuth-containing
      quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT,
      respectively, and those treated with a moxifloxacin-based triple regimen for 7
      and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori
      eradication was confirmed using the (13)C-urea breath test, rapid urease test or
      histology. RESULTS: The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were
      66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257),
      respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8%
      (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol
      analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT
      and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA
      treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443,
      respectively). CONCLUSIONS: The 7-BMT, 14-BMT, and 14-MA treatments showed
      similar and suboptimal efficacies. In both regimens, extending the duration of
      treatment may be reasonable considering the high level of antibiotic resistance
      in Korea.

PMID- 25071069
TI  - Cytokine expression of microscopic colitis including interleukin-17.
AB  - BACKGROUND/AIMS: Microscopic colitis is characterized by chronic watery diarrhea
      with specific pathological changes that can be diagnosed by microscopic
      examination. We performed immunohistochemical analysis of proinflammatory
      cytokines to investigate the pathogenic mechanism of microscopic colitis.
      METHODS: This study consisted of six patients with lymphocytic colitis, six
      patients with collagenous colitis, and six patients with functional diarrhea but
      normal pathology. We performed an immunohistochemical analysis of the colonic
      mucosal biopsies to assess the expression of cyclo-oxygenase-2, interleukin-17,
      nuclear factor-kappaB, interferon-gamma, inducible nitric oxide synthase, and
      tumor necrosis factor-alpha. We compared the quantity score of
      immunohistochemical staining among the groups. RESULTS: The microscopic colitis
      group showed significantly higher expression of cyclo-oxygenase-2, interleukin
      17, nuclear factor-kappaB, and interferon-gamma compared with the control group.
      Cytokine expression was similar between collagenous colitis and lymphocytic
      colitis. However, the expression of cyclo-oxygenase-2 was higher in collagenous
      colitis. CONCLUSIONS: Proinflammatory cytokines, including interleukin-17 and
      interferon-gamma, are highly expressed in microscopic colitis. The expression of
      cyclo-oxygenase-2 was higher in collagenous colitis than in lymphocytic colitis.
      This study is the first on interleukin-17 expression in microscopic colitis
      patients.

PMID- 25071070
TI  - Is a second-look endoscopy necessary after endoscopic submucosal dissection for
      gastric neoplasm?
AB  - BACKGROUND/AIMS: Second-look endoscopy is performed to check for the possibility
      of post-endoscopic submucosal dissection (ESD) bleeding and to perform
      prophylactic hemostasis in most hospitals; however, there is little evidence
      about the efficacy of second-look endoscopy. We investigated whether second-look
      endoscopy after ESD is useful in the prevention of post-ESD bleeding. METHODS: A
      total of 550 lesions with gastric epithelial neoplasms in 502 patients (372 men
      and 130 women) were treated with ESD between August 18, 2009 and August 18, 2010.
      After the exclusion of three lesions of post-ESD bleeding within 24 hours, 547
      lesions (335 early gastric cancers and 212 gastric adenomas) were included for
      the final analysis. RESULTS: The occurrence rate of delayed post-ESD bleeding was
      not significantly differ-ent between the second-look group and the no second-look
      group (1% vs 2.5%, p>0.05). The only predictor of delayed bleeding was tumor
      size, regardless of second-look endoscopy after ESD (22.8+/-9.87 vs 15.1+/-10.47,
      p<0.05). There was no difference between the prophylactic hemostasis and
      nonprophylactic hemostasis groups, including the occurrence rate of delayed
      bleeding. In the second-look group with prophylactic hemostasis, the hospital
      stay was more prolonged than in the second-look group without prophylactic
      hemostasis, but there was no significant difference (p=0.08). CONCLUSIONS: Second
      look endoscopy to prevent delayed bleeding after ESD provides no significant
      medical benefits.

PMID- 25071071
TI  - Expression of TIM-3, Human beta-defensin-2, and FOXP3 and Correlation with
      Disease Activity in Pediatric Crohn's Disease with Infliximab Therapy.
AB  - BACKGROUND/AIMS: This study investigated the expression of T cell immunoglobulin-
      and mucin-domain-containing molecule 3 (TIM-3), human beta-defensin (HBD)-2,
      forkhead box protein 3 (FOXP3), and the frequency of CD4(+) CD25(+) FOXP3(+)
      regulatory T cells (Tregs) in children with Crohn's disease (CD) during
      infliximab therapy. METHODS: We enrolled 20 CD patients who received infliximab
      treatment for 1 year. Peripheral blood and colonic mucosal specimens were
      collected from all CD patients and from healthy control individuals. RESULTS: A
      significant difference in TIM-3 mRNA expression was evident in peripheral blood
      mononuclear cells and colonic mucosa between CD patients before infliximab
      therapy and the healthy controls (p<0.001 and p=0.005, respectively). A
      significant difference in HBD-2 mRNA expression was found in colonic mucosa
      between CD patients before infliximab therapy and the healthy controls (p=0.013).
      In the active phase of CD, at baseline, the median percentage of T cells that
      were CD25(+) FOXP3(+) was 1.5% (range, 0.32% to 3.49%), which increased after
      inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008).
      CONCLUSIONS: Our study suggests that both the adaptive and innate immune systems
      are closely linked to each other in CD pathogenesis. And the results of our study
      indicate that it could be a useful therapeutic tool, where restoration of TIM-3,
      HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in
      CD.

PMID- 25071072
TI  - Effective biliary drainage and proper treatment improve outcomes of
      hepatocellular carcinoma with obstructive jaundice.
AB  - BACKGROUND/AIMS: We investigated the treatment outcomes and prognostic factors of
      hepatocellular carcinoma (HCC) with obstructive jaundice. METHODS: Among 2,861
      patients newly diagnosed with HCC between 2002 and 2011, a total of 63 patients
      who initially presented with obstructive jaundice were analyzed. Only four
      patients presented with resectable tumors and underwent curative resection. In
      the other patients who presented with unresectable tumors, 5, 8, 9, and 18
      patients received transarterial chemoembolization (TACE), chemotherapy,
      radiotherapy, and combined treatment, respectively. Both the clinical and the
      treatment factors that affect overall survival (OS) were analyzed. RESULTS: The
      median OS was 4 months, and the 1-year OS rate was 23%. Patients who received
      treatment for HCC had a significantly improved OS rate compared with the patients
      who received supportive care only (1-year OS, 32% vs 0%; p<0.01). Responders to
      treatment showed a better OS than nonresponders (1-year OS, 52% vs 0%; p<0.01).
      TACE and radiotherapy resulted in relatively good treatment responses of 64% and
      67%, respectively. In multivariate analyses, treatment of HCC (p=0.02) and the
      normalization of serum bilirubin by biliary drainage (p=0.02) were significantly
      favorable prognostic factors that affected the OS. CONCLUSIONS: Unresectable HCC
      with obstructive jaundice has a poor prognosis. However, effective biliary
      drainage and treatment of HCC such as with TACE or radiotherapy improves
      survival.

PMID- 25071073
TI  - Role of radiofrequency ablation in patients with hepatocellular carcinoma who
      undergo prior transarterial chemoembolization: long-term outcomes and predictive
      factors.
AB  - BACKGROUND/AIMS: The role of radiofrequency ablation (RFA) remains uncertain in
      patients with viable hepatocellular carcinoma (HCC) after transarterial
      chemoembolization (TACE). METHODS: A total of 101 patients (April 2007 to August
      2010) underwent RFA for residual or recurrent HCC after TACE. We analyzed their
      long-term outcomes and predictive factors. RESULTS: The overall survival rates
      after RFA were 93.1%, 65.4%, and 61.0% at 1, 3, and 5 years, respectively.
      Predictive factors for favorable overall survival were Child-Pugh class A (hazard
      ratio [HR], 3.45; p=0.001), serum alpha-fetoprotein (AFP) level <20 ng/mL (HR,
      2.90; p=0.02), and recurrent tumors after the last TACE (HR, 3.14; p=0.007). The
      cumulative recurrence-free survival rate after RFA at 6 months was 50.1%.
      Predictive factors for early recurrence (within 6 months) were serum AFP level
      >=20 ng/mL (HR, 3.02; p<0.001), tumor size >=30 mm at RFA (HR, 2.90; p=0.005),
      and nonresponse to the last TACE (HR, 2.13; p=0.013). CONCLUSIONS: Patients with
      recurrent or residual HCC who undergo prior TACE show a favorable overall
      survival, although their tumors seem to recur early and frequently. While good
      liver function, a low serum AFP level, and recurrent tumors were independent
      predictive factors for a favorable overall survival, poor response to TACE, a
      high serum AFP level, and large tumors are associated with early recurrence.

PMID- 25071074
TI  - Expression characteristics of KAI1 and vascular endothelial growth factor and
      their diagnostic value for hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: We tried to investigate the expression characteristics of KAI1,
      a suppressor of wide-spectrum tumor metastasis, and vascular endothelial growth
      factor (VEGF), the most common angiogenesis factor, and then to analyze their
      diagnostic value for hepatocellular carcinoma (HCC). METHODS: The protein and
      mRNA expression levels of KAI1 or VEGF in HCC tissues and in self-controlled para
      carcinoma tissues were analyzed by Western blot and real-time polymerase chain
      reaction, respectively. Serum levels of KAI1 and VEGF in the patients with HCC,
      benign liver disease or in healthy controls were quantitatively detected by
      enzyme-linked immunosorbent assay. RESULTS: The expression level of KAI1 was
      downregulated, while the expression level of VEGF was upregulated in the tissues
      or serum of the patients with HCC. The expression level of serum KAI1 in HCC
      patients was correlated with TNM staging, intrahepatic metastasis, lymph node or
      peritoneal metastasis, and portal vein thrombus. In addition to the factors that
      were correlated with KAI1 expression, VEGF expression was also closely related to
      the alpha-fetoprotein level of the patients. The area under the receiver
      operating characteristic curve for the diagnosis of HCC was 0.907 for KAI1 and
      0.779 for VEGF. The sensitivity of serum KAI1 levels in the diagnosis of HCC was
      86.96%; the accuracy was 83.06%, while the sensitivity, the accuracy and the
      negative predictive value were improved to 91.86%, 84.68%, and 78.79% according
      to the combined detection of KAI1 and VEGF, respectively. CONCLUSIONS: A combined
      detection of KAI1 and VEGF may greatly improve the efficiency of diagnosis and
      form a reliable panel of diagnostic markers for HCC.

PMID- 25071075
TI  - A very low-carbohydrate, low-saturated fat diet for type 2 diabetes management: a
      randomized trial.
AB  - OBJECTIVE: To comprehensively compare the effects of a very low-carbohydrate,
      high-unsaturated/low-saturated fat diet (LC) with those of a high-unrefined
      carbohydrate, low-fat diet (HC) on glycemic control and cardiovascular disease
      (CVD) risk factors in type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS: Obese
      adults (n = 115, BMI 34.4 +/- 4.2 kg/m(2), age 58 +/- 7 years) with T2DM were
      randomized to a hypocaloric LC diet (14% carbohydrate [<50 g/day], 28% protein,
      and 58% fat [<10% saturated fat]) or an energy-matched HC diet (53% carbohydrate,
      17% protein, and 30% fat [<10% saturated fat]) combined with structured exercise
      for 24 weeks. The outcomes measured were as follows: glycosylated hemoglobin
      (HbA1c), glycemic variability (GV; assessed by 48-h continuous glucose
      monitoring), antiglycemic medication changes (antiglycemic medication effects
      score [MES]), and blood lipids and pressure. RESULTS: A total of 93 participants
      completed 24 weeks. Both groups achieved similar completion rates (LC 79%, HC
      82%) and weight loss (LC -12.0 +/- 6.3 kg, HC -11.5 +/- 5.5 kg); P >= 0.50. Blood
      pressure (-9.8/-7.3 +/- 11.6/6.8 mmHg), fasting blood glucose (-1.4 +/- 2.3
      mmol/L), and LDL cholesterol (-0.3 +/- 0.6 mmol/L) decreased, with no diet effect
      (P >= 0.10). LC achieved greater reductions in triglycerides (-0.5 +/- 0.5 vs. 
      0.1 +/- 0.5 mmol/L), MES (-0.5 +/- 0.5 vs. -0.2 +/- 0.5), and GV indices; P <=
      0.03. LC induced greater HbA1c reductions (-2.6 +/- 1.0% [-28.4 +/- 10.9
      mmol/mol] vs. -1.9 +/- 1.2% [-20.8 +/- 13.1 mmol/mol]; P = 0.002) and HDL
      cholesterol (HDL-C) increases (0.2 +/- 0.3 vs. 0.05 +/- 0.2 mmol/L; P = 0.007) in
      participants with the respective baseline values HbA1c >7.8% (62 mmol/mol) and
      HDL-C <1.29 mmol/L. CONCLUSIONS: Both diets achieved substantial improvements for
      several clinical glycemic control and CVD risk markers. These improvements and
      reductions in GV and antiglycemic medication requirements were greatest with the
      LC compared with HC. This suggests an LC diet with low saturated fat may be an
      effective dietary approach for T2DM management if effects are sustained beyond 24
      weeks.

PMID- 25071076
TI  - Early atherosclerosis relates to urinary albumin excretion and cardiovascular
      risk factors in adolescents with type 1 diabetes: Adolescent type 1 Diabetes
      cardio-renal Intervention Trial (AdDIT).
AB  - OBJECTIVE: The origins of cardiovascular and renal disease in type 1 diabetes
      begin during childhood. We aimed to evaluate carotid (cIMT) and aortic intima
      media thickness (aIMT) and their relationship with cardiovascular risk factors
      and urinary albumin excretion in adolescents with type 1 diabetes in the
      Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT). RESEARCH
      DESIGN AND METHODS: A total of 406 adolescents with type 1 diabetes, who were
      14.1 +/- 1.9 years old with type 1 diabetes duration of 6.7 +/- 3.7 years, and 57
      age-matched control subjects provided clinical and biochemical data and
      ultrasound measurements of vascular structure (cIMT and aIMT). Vascular
      endothelial and smooth muscle function was also measured in 123 of 406 with type
      1 diabetes and all control subjects. RESULTS: In type 1 diabetic subjects,
      mean/maximal aIMT (P < 0.006; <0.008), but not mean/maximal cIMT, was greater
      than in control subjects. Mean/maximal aIMT related to urinary albumin-to
      creatinine ratio (multiple regression coefficient [SE], 0.013 [0.006], P = 0.03;
      0.023 [0.007], P = 0.002), LDL cholesterol (0.019 [0.008], P = 0.02; 0.025
      [0.011], P = 0.02), and age (0.010 [0.004], P = 0.004; 0.012 [0.005], P = 0.01),
      independent of other variables. Mean/maximal cIMT was greater in males (0.023
      [0.006], P = 0.02; 0.029 [0.007], P < 0.0001), and mean cIMT related
      independently to systolic blood pressure (0.001 [0.001], P = 0.04). Vascular
      smooth muscle function related to aIMT and cIMT but not to urinary albumin
      excretion. CONCLUSIONS: aIMT may be a more sensitive marker of atherosclerosis
      than cIMT in type 1 diabetes during mid-adolescence. Higher urinary albumin
      excretion, even within the normal range, is associated with early atherosclerosis
      and should direct clinical attention to modifiable cardiovascular risk factors.

PMID- 25071077
TI  - Insulin sensitivity is an important determinant of renal health in adolescents
      with type 2 diabetes.
AB  - OBJECTIVE: Diabetic nephropathy (DN) remains the most common cause of end-stage
      renal disease and is a major cause of mortality in type 2 diabetes. Insulin
      sensitivity is an important determinant of renal health in adults with type 2
      diabetes, but limited data exist in adolescents. We hypothesized that measured
      insulin sensitivity (glucose infusion rate [GIR]) would be associated with early
      markers of DN reflected by estimated glomerular filtration rate (eGFR) and
      albumin-creatinine ratio (ACR) in adolescents with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: Type 2 diabetic (n = 46), obese (n = 29), and lean (n = 19)
      adolescents (15.1 +/- 2.2 years) had GIR measured by hyperinsulinemic-euglycemic
      clamps. ACR was measured and GFR was estimated by the Bouvet equation (combined
      creatinine and cystatin C). RESULTS: Adolescents with type 2 diabetes had
      significantly lower GIR, and higher eGFR and ACR than obese or lean adolescents.
      Moreover, 34% of type 2 diabetic adolescents had albuminuria (ACR >=30 mg/g), and
      24% had hyperfiltration (>=135 mL/min/1.73 m2). Stratifying ACR and eGFR into
      tertiles, adolescents with type 2 diabetes in the highest tertiles of ACR and
      eGFR had respectively lower GIR than those in the mid and low tertiles, after
      adjusting for age, sex, Tanner stage, BMI, and HbA1c (P = 0.02 and P = 0.04).
      GIR, but not HbA1c, LDL, or systolic blood pressure, was also associated with
      eGFR after adjusting for sex and Tanner stage (beta +/- SE: -2.23 +/- 0.87; P =
      0.02). CONCLUSIONS: A significant proportion of adolescents with type 2 diabetes
      showed evidence of early DN, and insulin sensitivity, rather than HbA1c, blood
      pressure, or lipid control, was the strongest determinant of renal health.

PMID- 25071078
TI  - Falling insulin requirements are associated with adverse obstetric outcomes in
      women with preexisting diabetes.
AB  - OBJECTIVE: To investigate the clinical significance of falling insulin
      requirements in women with preexisting or overt diabetes in pregnancy. RESEARCH
      DESIGN AND METHODS: A retrospective review of 139 pregnancies was conducted in
      women, with preexisting diabetes, delivering between January 2010 and January
      2013. Women with falling insulin requirements of 15% or more from the peak total
      daily dose in late pregnancy were considered case subjects (n = 35). The primary
      outcome consisted of a composite of clinical markers of placental dysfunction,
      including preeclampsia, small for gestational age (SGA, <=5th percentile for
      gestational age), stillbirth (>20 weeks), and premature delivery (<=30 weeks).
      RESULTS: A total of 25.2% of women had >15% fall in insulin requirements with
      nulliparity as the only predictor at baseline (odds ratio [OR] 2.5 [95% CI 1.1
      5.7], P = 0.03). Falling insulin requirements were associated with an increased
      risk of preeclampsia (OR 3.5 [1.1-10.7], P < 0.05) and the composite of clinical
      markers of placental dysfunction (4.4 [1.73-11.26], P = 0.002). Although falling
      insulin requirements were associated with higher rates of SGA (3.4 [1.0-11.3], P
      = 0.048), they were not associated with other adverse neonatal outcomes. However,
      there was a higher incidence of neonatal intensive care unit admission (15.5 [3.1
      77.6], P = 0.001) and earlier delivery in this group (median 37.7 weeks [IQR 34.3
      38.4] vs. 38.3 weeks [37.4-38.9], P = 0.014). CONCLUSIONS: Falling insulin
      requirements, in women with preexisting diabetes, are associated with an
      increased risk of complications related to placental dysfunction. Further
      prospective studies are needed to guide clinical management.

PMID- 25071080
TI  - Dirac model of electronic transport in graphene antidot barriers.
AB  - In order to use graphene for semiconductor applications, such as transistors with
      high on/off ratios, a band gap must be introduced into this otherwise
      semimetallic material. A promising method of achieving a band gap is by
      introducing nanoscale perforations (antidots) in a periodic pattern, known as a
      graphene antidot lattice (GAL). A graphene antidot barrier (GAB) can be made by
      introducing a 1D GAL strip in an otherwise pristine sheet of graphene. In this
      paper, we will use the Dirac equation (DE) with a spatially varying mass term to
      calculate the electronic transport through such structures. Our approach is much
      more general than previous attempts to use the Dirac equation to calculate
      scattering of Dirac electrons on antidots. The advantage of using the DE is that
      the computational time is scale invariant and our method may therefore be used to
      calculate properties of arbitrarily large structures. We show that the results of
      our Dirac model are in quantitative agreement with tight-binding for hexagonal
      antidots with armchair edges. Furthermore, for a wide range of structures, we
      verify that a relatively narrow GAB, with only a few antidots in the unit cell,
      is sufficient to give rise to a transport gap. 

PMID- 25071079
TI  - The draft genome and transcriptome of Amaranthus hypochondriacus: a C4 dicot
      producing high-lysine edible pseudo-cereal.
AB  - Grain amaranths, edible C4 dicots, produce pseudo-cereals high in lysine. Lysine
      being one of the most limiting essential amino acids in cereals and C4
      photosynthesis being one of the most sought-after phenotypes in protein-rich
      legume crops, the genome of one of the grain amaranths is likely to play a
      critical role in crop research. We have sequenced the genome and transcriptome of
      Amaranthus hypochondriacus, a diploid (2n = 32) belonging to the order
      Caryophyllales with an estimated genome size of 466 Mb. Of the 411 linkage single
      nucleotide polymorphisms (SNPs) reported for grain amaranths, 355 SNPs (86%) are
      represented in the scaffolds and 74% of the 8.6 billion bases of the sequenced
      transcriptome map to the genomic scaffolds. The genome of A. hypochondriacus,
      codes for at least 24,829 proteins, shares the paleohexaploidy event with species
      under the superorders Rosids and Asterids, harbours 1 SNP in 1,000 bases, and
      contains 13.76% of repeat elements. Annotation of all the genes in the lysine
      biosynthetic pathway using comparative genomics and expression analysis offers
      insights into the high-lysine phenotype. As the first grain species under
      Caryophyllales and the first C4 dicot genome reported, the work presented here
      will be beneficial in improving crops and in expanding our understanding of
      angiosperm evolution. 

PMID- 25071081
TI  - Cardiac myocyte-derived follistatin-like 1 prevents renal injury in a subtotal
      nephrectomy model.
AB  - Heart disease contributes to the progression of CKD. Heart tissue produces a
      number of secreted proteins, also known as cardiokines, which participate in
      intercellular and intertissue communication. We recently reported that
      follistatin-like 1 (Fstl1) functions as a cardiokine with cardioprotective
      properties. Here, we investigated the role of cardiac Fstl1 in renal injury after
      subtotal nephrectomy. Cardiac-specific Fstl1-deficient (cFstl1-KO) mice and wild
      type mice were subjected to subtotal (5/6) nephrectomy. cFstl1-KO mice showed
      exacerbation of urinary albumin excretion, glomerular hypertrophy, and
      tubulointerstitial fibrosis after subtotal renal ablation compared with wild-type
      mice. cFstl1-KO mice also exhibited increased mRNA levels of proinflammatory
      cytokines, including TNF-alpha and IL-6, NADPH oxidase components, and fibrotic
      mediators, in the remnant kidney. Conversely, systemic administration of
      adenoviral vectors expressing Fstl1 (Ad-Fstl1) to wild-type mice with subtotal
      nephrectomy led to amelioration of albuminuria, glomerular hypertrophy, and
      tubulointerstitial fibrosis, accompanied by reduced expression of proinflammatory
      mediators, NADPH oxidase components, and fibrotic markers in the remnant kidney.
      In cultured human mesangial cells, treatment with recombinant FSTL1 attenuated
      TNF-alpha-stimulated expression of proinflammatory cytokines. Treatment of
      mesangial cells with FSTL1 augmented the phosphorylation of AMP-activated protein
      kinase (AMPK), and inhibition of AMPK activation abrogated the anti-inflammatory
      effects of FSTL1. These data suggest that Fstl1 functions in cardiorenal
      communication and that the lack of Fstl1 production by myocytes promotes
      glomerular and tubulointerstitial damage in the kidney. 

PMID- 25071082
TI  - Epigenetic regulation of microRNAs controlling CLDN14 expression as a mechanism
      for renal calcium handling.
AB  - The kidney has a major role in extracellular calcium homeostasis. Multiple
      genetic linkage and association studies identified three tight junction genes
      from the kidney--claudin-14, -16, and -19--as critical for calcium imbalance
      diseases. Despite the compelling biologic evidence that the claudin-14/16/19
      proteins form a regulated paracellular pathway for calcium reabsorption,
      approaches to regulate this transport pathway are largely unavailable, hindering
      the development of therapies to correct calcium transport abnormalities. Here, we
      report that treatment with histone deacetylase (HDAC) inhibitors downregulates
      renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice.
      Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription
      of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress
      the expression of claudin-14, the negative regulator of the paracellular pathway.
      With renal clearance and tubule perfusion techniques, we showed that HDAC
      inhibitors transiently increase the paracellular cation conductance in the thick
      ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in
      mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the
      calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH)
      repressed the transcription of miR-9 and miR-374 genes, and treatment with an
      HDAC inhibitor rescued the phenotypes of cell and animal models of ADH.
      Furthermore, systemic treatment of mice with antagomiRs against these miRs
      relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together,
      our findings provide proof of concept for a novel therapeutic principle on the
      basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases.

PMID- 25071083
TI  - Rhophilin-1 is a key regulator of the podocyte cytoskeleton and is essential for
      glomerular filtration.
AB  - Rhophilin-1 is a Rho GTPase-interacting protein, the biologic function of which
      is largely unknown. Here, we identify and describe the functional role of
      Rhophilin-1 as a novel podocyte-specific protein of the kidney glomerulus.
      Rhophilin-1 knockout mice were phenotypically normal at birth but developed
      albuminuria at about 2 weeks of age. Kidneys from severely albuminuric mice
      revealed widespread podocyte foot process effacement, thickening of the
      glomerular basement membrane, and FSGS-like lesions. The absence of any overt
      changes in the expression of podocyte proteins at the onset of proteinuria
      suggested that the primary cause of podocyte abnormalities in Rhpn1-null mice was
      the result of cell-autonomous, Rhophilin-1-dependent signaling events. In
      culture, Rhophilin-1 was detected at the plasma membrane leading edge of primary
      podocytes, where it elicited remodeling of the actin cytoskeleton network. This
      effect of Rhophilin-1 on actin cytoskeleton organization associated with
      inhibitory effects on Rho-dependent phosphorylation of the myosin regulatory
      light chain and stress fiber formation. Conversely, phosphorylation of myosin
      regulatory light chain increased in podocyte foot processes of Rhpn1(-/-) mice,
      implicating altered actinomyosin contractility in foot process effacement and
      compromised filtration capacity. Targeted deletion of RhoA in podocytes of
      Rhophilin-1 knockout mice exacerbated the renal injury. Taken together, our
      results indicate that Rhophilin-1 is essential for the integrity of the
      glomerular filtration barrier and that this protein is a key determinant of
      podocyte cytoskeleton architecture. 

PMID- 25071084
TI  - Association of early kidney allograft failure with preformed IgA antibodies to
      beta2-glycoprotein I.
AB  - In the current immunosuppressive therapy era, vessel thrombosis is the most
      common cause of early graft loss after renal transplantation. The prevalence of
      IgA anti-beta2-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis
      is elevated (>30%), and these antibodies correlate with mortality and
      cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients
      with transplants, we followed all patients transplanted from 2000 to 2002 in the
      Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in
      pretransplant serum was examined retrospectively. Of 269 patients, 89 patients
      were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were
      negative (67%; group 2). Graft loss at 6 months post-transplant was significantly
      higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The
      most frequent cause of graft loss was thrombosis of the vessels, which was
      observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04).
      Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an
      independent risk factor for early graft loss (P=0.04) and delayed graft function
      (P=0.04). There were no significant differences regarding patient survival
      between the two groups. Graft survival was similar in both groups after 6 months.
      In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of
      early graft loss caused by thrombosis and a high risk of delayed graft function.
      Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early
      clinical outcomes after renal transplantation. 

PMID- 25071085
TI  - Inhibition of intracellular clusterin attenuates cell death in nephropathic
      cystinosis.
AB  - Nephropathic cystinosis, characterized by accumulation of cystine in the
      lysosomes, is caused by mutations in CTNS. The molecular and cellular mechanisms
      underlying proximal tubular dysfunction and progressive renal failure in
      nephropathic cystinosis are largely unclear, and increasing evidence supports the
      notion that cystine accumulation alone is not responsible for the end organ
      injury in cystinosis. We previously identified clusterin as potentially involved
      in nephropathic cystinosis. Here, we studied the expression of clusterin in renal
      proximal tubular epithelial cells obtained from patients with nephropathic
      cystinosis. The cytoprotective secretory form of clusterin, as evaluated by
      Western blot analysis, was low or absent in cystinosis cells compared with normal
      primary cells. Confocal microscopy revealed elevated levels of intracellular
      clusterin in cystinosis cells. Clusterin in cystinosis cells localized to the
      nucleus and cytoplasm and showed a filamentous and punctate aggresome-like
      pattern compared with diffuse cytoplasmic staining in normal cells. In kidney
      biopsy samples from patients with nephropathic cystinosis, clusterin protein
      expression was mainly limited to the proximal tubular cells. Furthermore,
      expression of clusterin overlapped with the expression of apoptotic proteins
      (apoptosis-inducing factor and cleaved caspase-3) and autophagy proteins (LC3 II
      and p62). Silencing of the clusterin gene resulted in a significant increase in
      cell viability and attenuation of apoptosis in cystinosis cells. Results of this
      study identify clusterin as a pivotal factor in the cell injury mechanism of
      nephropathic cystinosis and provide evidence linking cellular stress and injury
      to Fanconi syndrome and progressive renal injury in nephropathic cystinosis. 

PMID- 25071086
TI  - Hypertension is a major contributor to 20-hydroxyeicosatetraenoic acid-mediated
      kidney injury in diabetic nephropathy.
AB  - In the kidney, 20-hydroxyeicosatetraenoic acid (20-HETE) is a primary cytochrome
      P450 4 (Cyp4)-derived eicosanoid that enhances vasoconstriction of renal vessels
      and induces hypertension, renal tubular cell hypertrophy, and podocyte apoptosis.
      Hypertension and podocyte injury contribute to diabetic nephropathy and are
      strong predictors of disease progression. In this study, we defined the
      mechanisms whereby 20-HETE affects the progression of diabetic nephropathy. We
      used Cyp4a14KO male mice that exhibit androgen-sensitive hypertension due to
      increased Cyp4a12-mediated 20-HETE production. We show that, upon induction of
      diabetes type 1 via streptozotocin injection, Cyp4a14KO male mice developed worse
      renal disease than streptozotocin-treated wild-type mice, characterized by
      increased albuminuria, mesangial expansion, glomerular matrix deposition, and
      thickness of the glomerular basement membranes. Castration blunted androgen
      mediated Cyp4a12 synthesis and 20-HETE production, normalized BP, and ameliorated
      renal damage in diabetic Cyp4a14KO mice. Notably, treatment with a 20-HETE
      antagonist or agents that normalized BP without affecting Cyp4a12 expression and
      20-HETE biosynthesis also ameliorated diabetes-mediated renal damage and
      albuminuria in Cyp4a14KO male mice. Taken together, these results suggest that
      hypertension is the major contributor to 20-HETE-driven diabetes-mediated kidney
      injury. 

PMID- 25071087
TI  - Mutual antagonism of Wilms' tumor 1 and beta-catenin dictates podocyte health and
      disease.
AB  - Activation of beta-catenin, the intracellular mediator of canonical Wnt
      signaling, has a critical role in mediating podocyte injury and proteinuria.
      However, the underlying mechanisms remain poorly understood. Here, we show that
      beta-catenin triggers ubiquitin-mediated protein degradation of Wilms' tumor 1
      (WT1) and functionally antagonizes its action. In mice injected with adriamycin,
      WT1 protein was progressively lost in glomerular podocytes at 1, 3, and 5 weeks
      after injection. Notably, loss of WT1 apparently did not result from podocyte
      depletion but was closely associated with upregulation of beta-catenin. This
      change in WT1/beta-catenin ratio was accompanied by loss of podocyte-specific
      nephrin, podocalyxin, and synaptopodin and acquisition of mesenchymal markers
      Snail1, alpha-smooth muscle actin, and fibroblast-specific protein 1. In vitro,
      overexpression of beta-catenin induced WT1 protein degradation through the
      ubiquitin proteasomal pathway, which was blocked by MG-132. WT1 and beta-catenin
      also competed for binding to common transcriptional coactivator CREB-binding
      protein and mutually repressed the expression of their respective target genes.
      In glomerular miniorgan culture, activation of beta-catenin by Wnt3a repressed
      WT1 and its target gene expression. In vivo, blockade of Wnt/beta-catenin
      signaling by endogenous antagonist Klotho induced WT1 and restored podocyte
      integrity in adriamycin nephropathy. These results show that beta-catenin
      specifically targets WT1 for ubiquitin-mediated degradation, leading to podocyte
      dedifferentiation and mesenchymal transition. Our data also suggest that WT1 and
      beta-catenin have opposing roles in podocyte biology, and that the ratio of their
      expression levels dictates the state of podocyte health and disease in vivo. 

PMID- 25071088
TI  - Mechanisms of renal control of potassium homeostasis in complete aldosterone
      deficiency.
AB  - Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied
      aldosterone synthase knockout (AS(-/-)) mice to define renal control mechanisms
      of K(+) homeostasis in complete aldosterone deficiency. AS(-/-) mice were
      normokalemic and tolerated a physiologic dietary K(+) load (2% K(+), 2 days)
      without signs of illness, except some degree of polyuria. With supraphysiologic
      K(+) intake (5% K(+)), AS(-/-) mice decompensated and became hyperkalemic. High
      K(+) diets induced upregulation of the renal outer medullary K(+) channel in AS(
      /-) mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient
      to increase the electrochemical driving force for K(+) excretion was detected
      only with a 2% K(+) diet. Phosphorylation of the thiazide-sensitive NaCl
      cotransporter was consistently lower in AS(-/-) mice than in AS(+/+) mice and was
      downregulated in mice of both genotypes in response to increased K(+) intake.
      Inhibition of the angiotensin II type 1 receptor reduced renal creatinine
      clearance and apical ENaC localization, and caused severe hyperkalemia in AS(-/-)
      mice. In contrast with the kidney, the distal colon of AS(-/-) mice did not
      respond to dietary K(+) loading, as indicated by Ussing-type chamber experiments.
      Thus, renal adaptation to a physiologic, but not supraphysiologic, K(+) load can
      be achieved in aldosterone deficiency by aldosterone-independent activation of
      the renal outer medullary K(+) channel and ENaC, to which angiotensin II may
      contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive
      NaCl cotransporter may support renal adaptation by activation of flow-dependent
      K(+) secretion and increased intratubular availability of Na(+) that can be
      reabsorbed in exchange for K(+) secreted. 

PMID- 25071089
TI  - Chronic hypoxia-inducible transcription factor-2 activation stably transforms
      juxtaglomerular renin cells into fibroblast-like cells in vivo.
AB  - On the basis of previous observations that deletion of the von Hippel-Lindau
      protein (pVHL) in juxtaglomerular (JG) cells of the kidney suppresses renin and
      induces erythropoietin expression, this study aimed to characterize the events
      underlying this striking change of hormone expression. We found that renin cell
      specific deletion of pVHL in mice leads to a phenotype switch in JG cells, from a
      cuboid and multiple vesicle-containing form into a flat and elongated form
      without vesicles. This shift of cell phenotype was accompanied by the
      disappearance of marker proteins for renin cells (e.g., aldo-keto reductase
      family 1, member 7 and connexin 40) and by the appearance of markers of
      fibroblast-like cells (e.g., collagen I, ecto-5'-nucleotidase, and PDGF receptor
      beta). Furthermore, hypoxia-inducible transcription factor-2alpha (HIF-2alpha)
      protein constitutively accumulated in these transformed cells. Codeletion of pVHL
      and HIF-2alpha in JG cells completely prevented the phenotypic changes. Similar
      to renin expression in normal JG cells, angiotensin II negatively regulated
      erythropoietin expression in the transformed cells. In summary, chronic
      activation of HIF-2 in renal JG cells leads to a reprogramming of the cells into
      fibroblast-like cells resembling native erythropoietin-producing cells located in
      the tubulointerstitium. 

PMID- 25071091
TI  - First principles study of fluorine substitution on two-dimensional germanane.
AB  - Using first principles calculations with hybrid exchange-correlation functional,
      we investigate the electronic structure of germanane and fluorinated germanane.
      We find that the band gap of fluorinated germanane decreases with the increasing
      of fluorine coverage, regardless of fluorine distribution on the surface. Our
      results indicate that chemical functionalization could be used easily to control
      the band gap of the germanane from 1.55 eV (pure germanane) to 0.17 eV (fully
      fluorinated germanane). It also shows good potentiality as a photocatalytic
      material for water splitting, as well as a two-dimensional functional material
      for optoelectronic and sensing applications.

PMID- 25071090
TI  - Restoration of renal function does not correct impairment of uremic HDL
      properties.
AB  - Cardiovascular disease remains the leading cause of death in renal transplant
      recipients, but the underlying causative mechanisms for this important problem
      remain elusive. Recent work has indicated that qualitative alterations of HDL
      affect its functional and compositional properties in ESRD. Here, we
      systematically analyzed HDL from stable renal transplant recipients, according to
      graft function, and from patients with ESRD to determine whether structural and
      functional properties of HDL remain dysfunctional after renal transplantation.
      Cholesterol acceptor capacity and antioxidative activity, representing two key
      cardioprotective mechanisms of HDL, were profoundly suppressed in kidney
      transplant recipients independent of graft function and were comparable with
      levels in patients with ESRD. Using a mass spectroscopy approach, we identified
      specific remodeling of transplant HDL with highly enriched proteins, including
      alpha-1 microglobulin/bikunin precursor, pigment epithelium-derived factor,
      surfactant protein B, and serum amyloid A. In conclusion, this study demonstrates
      that HDL from kidney recipients is uniquely altered at the molecular and
      functional levels, indicating a direct pathologic role of HDL that could
      contribute to the substantial cardiovascular risk in the transplant population. 

PMID- 25071092
TI  - Reliability evaluation of thermophysical properties from first-principles
      calculations.
AB  - Thermophysical properties, such as heat capacity, bulk modulus and thermal
      expansion, are of great importance for many technological applications and are
      traditionally determined experimentally. With the rapid development of
      computational methods, however, first-principles computed temperature-dependent
      data are nowadays accessible. We evaluate various computational realizations of
      such data in comparison to the experimental scatter. The work is focussed on the
      impact of different first-principles codes (QUANTUM ESPRESSO and VASP),
      pseudopotentials (ultrasoft and projector augmented wave) as well as phonon
      determination methods (linear response and direct force constant method) on these
      properties. Based on the analysis of data for two pure elements, Cr and Ni,
      consequences for the reliability of temperature-dependent first-principles data
      in computational thermodynamics are discussed.

PMID- 25071093
TI  - Non-invasive fetal ECG analysis.
AB  - Despite the important advances achieved in the field of adult electrocardiography
      signal processing, the analysis of the non-invasive fetal electrocardiogram (NI
      FECG) remains a challenge. Currently no gold standard database exists which
      provides labelled FECG QRS complexes (and other morphological parameters), and
      publications rely either on proprietary databases or a very limited set of data
      recorded from few (or more often, just one) individuals.The PhysioNet/Computing
      in Cardiology Challenge 2013 enables to tackle some of these limitations by
      releasing a set of NI-FECG data publicly to the scientific community in order to
      evaluate signal processing techniques for NI-FECG extraction. The Challenge aim
      was to encourage development of accurate algorithms for locating QRS complexes
      and estimating the QT interval in non-invasive FECG signals. Using carefully
      reviewed reference QRS annotations and QT intervals as a gold standard, based on
      simultaneous direct FECG when possible, the Challenge was designed to measure and
      compare the performance of participants' algorithms objectively. Multiple
      challenge events were designed to test basic FHR estimation accuracy, as well as
      accuracy in measurement of inter-beat (RR) and QT intervals needed as a basis for
      derivation of other FECG features.This editorial reviews the background issues,
      the design of the Challenge, the key achievements, and the follow-up research
      generated as a result of the Challenge, published in the concurrent special issue
      of Physiological Measurement. 

PMID- 25071094
TI  - An ECG simulator for generating maternal-foetal activity mixtures on abdominal
      ECG recordings.
AB  - Accurate foetal electrocardiogram (FECG) morphology extraction from non-invasive
      sensors remains an open problem. This is partly due to the paucity of available
      public databases. Even when gold standard information (i.e derived from the scalp
      electrode) is present, the collection of FECG can be problematic, particularly
      during stressful or clinically important events.In order to address this problem
      we have introduced an FECG simulator based on earlier work on foetal and adult
      ECG modelling. The open source foetal ECG synthetic simulator, fecgsyn, is able
      to generate maternal-foetal ECG mixtures with realistic amplitudes, morphology,
      beat-to-beat variability, heart rate changes and noise. Positional (rotation and
      translation-related) movements in the foetal and maternal heart due to
      respiration, foetal activity and uterine contractions were also added to the
      simulator.The simulator was used to generate some of the signals that were part
      of the 2013 PhysioNet Computing in Cardiology Challenge dataset and has been
      posted on Physionet.org (together with scripts to generate realistic scenarios)
      under an open source license. The toolbox enables further research in the field
      and provides part of a standard for industry and regulatory testing of rare
      pathological scenarios. 

PMID- 25071095
TI  - Robust fetal ECG extraction and detection from abdominal leads.
AB  - The fetal ECG derived from abdominal leads provides an alternative to standard
      means of fetal monitoring. Furthermore, it permits long-term and ambulant
      recordings, which expands the range diagnostic possibilities for evaluating the
      fetal health state. However, due to the temporal and spectral overlap of maternal
      and fetal signals, the usage of abdominal leads imposes the need for elaborated
      signal processing routines.In this work a modular combination of processing
      techniques is presented. Its core consists of two maternal ECG estimation
      techniques, namely the extended Kalman smoother (EKS) and template adaption (TA)
      in combination with an innovative detection algorithm. Our detection method
      employs principles of evolutionary computing to detect fetal peaks by considering
      the periodicity and morphological characteristics of the fetal signal. In a
      postprocessing phase, single channel detections are combined by means of kernel
      density estimation and heart rate correction.The described methodology was
      presented during the Computing in Cardiology Challenge 2013. The entry was the
      winner of the closed-source events with average scores for events 4/5 with
      15.1/3.32 (TA) and 69.5/4.58 (EKS) on training set-A and 20.4/4.57 (TA) and
      219/7.69 (EKS) on test set-B, respectively. Using our own clinical data (24
      subjects each 20 min recordings) and statistical measures beyond the Challenge's
      scoring system, we further validated the proposed method. For our clinical data
      we obtained an average detection rate of 82.8% (TA) and 83.4% (EKS). The achieved
      results show that the proposed methods are able produce reliable fetal heart rate
      estimates from a restricted number of abdominal leads. 

PMID- 25071096
TI  - Absolute quantitation of myocardial blood flow in human subjects with or without
      myocardial ischemia using dynamic flurpiridaz F 18 PET.
AB  - Absolute quantitation of myocardial blood flow (MBF) by PET is an established
      method of analyzing coronary artery disease (CAD) but subject to the various
      shortcomings of available radiotracers. Flurpiridaz F 18 is a novel PET
      radiotracer that exhibits properties of an ideal tracer. METHODS: A new absolute
      perfusion quantitation method with flurpiridaz was developed, taking advantage of
      the early kinetics and high first-pass extraction by the myocardium of this
      radiotracer, and the first-in-human measurements of MBF performed in 7 healthy
      subjects and 8 patients with documented CAD. PET images with time-activity curves
      were acquired at rest and during adenosine stress. RESULTS: In healthy subjects,
      regional MBF between coronary artery territories did not differ significantly,
      leading to a mean global MBF of 0.73 mL/min/g at rest and 2.53 mL/min/g during
      stress, with a mean global myocardial flow reserve (MFR) of 3.70. CAD vascular
      territories with <50% stenosis demonstrated a mean MBF of 0.73 at rest and 2.02
      during stress, leading to a mean MFR of 2.97. CAD vascular territories with >=50%
      stenosis exhibited a mean MBF of 0.86 at rest and 1.43 during stress, leading to
      a mean MFR of 1.86. Differences in stress MBF and MFR between normal and CAD
      territories, as well as between <50% and >=50% stenosis vascular territories,
      were significant (P < 0.01). CONCLUSION: Absolute quantitation of MBF in humans
      with the novel PET radiotracer flurpiridaz is feasible over a wide range of
      cardiac flow in the presence or absence of stress-inducible myocardial ischemia.
      The significant decrease in stress MBF and ensuing MFR in CAD territories allows
      a clear distinction between vascular territories exhibiting stress-inducible
      myocardial ischemia and those with normal perfusion.

PMID- 25071097
TI  - Distinctive in vivo kinetics of the new sigma1 receptor ligands (R)-(+)- and (S)
      (-)-18F-fluspidine in porcine brain.
AB  - Because of their involvement in growth and survival signaling cascades, the
      sigma(1) receptors (sigma(1)Rs) represent a novel target for the treatment of
      cancer and several brain diseases such as depression and neurodegeneration. From
      a series of sigma1R-specific (18)F-fluoroalkylated spirocyclic piperidines, we
      have chosen (18)F-fluspidine for detailed investigation of the in vivo kinetics
      of the (R)-(+)- and (S)-(-)-enantiomers to identify their potential for imaging
      in humans. METHODS: Enantiopure tosylate precursors for radiolabeling were
      obtained using chiral preparative high-performance liquid chromatography and used
      for radiosynthesis of both (18)F-fluspidine enantiomers by nucleophilic
      substitution with K-(18)F-F-Kryptofix 222-carbonate complex in a synthesis
      module. Brain pharmacokinetics were investigated by dynamic PET studies in
      piglets under baseline and blocking conditions using the highly selective sigma1R
      agonist SA4503. Standardized uptake values (SUVs) were calculated for 24 MR
      defined brain regions. Total distribution volume (V(T)) and binding potentials
      (k3'/k4) of (S)-(-)- and (R)-(+)-(18)F-fluspidine were estimated. Furthermore,
      V(T) values were estimated by graphical analysis using Logan plots. RESULTS: The
      (S)- and (R)-tosylates were obtained in excellent enantiomeric purities (>98% and
      >96% enantiomeric excess, respectively). (S)-(-)- and (R)-(+)-(18)F-fluspidine
      were synthesized within approximately 70 min (radiochemical yield, 35%-45%;
      specific activity, 650-870 GBq/MUmol; radiochemical purity, >99%). Both
      radiotracers displayed different brain uptake kinetics. Although the initial
      brain uptake was similar, the SUV at the end of the study differed significantly
      (P < 0.05), with (R)-(+)-(18)F-fluspidine showing about 60%-150% higher values.
      Administration of SA4503 reduced SUV almost equally for both radiotracers by
      approximately 65%. Furthermore, k(3)' was significantly decreased under blocking
      conditions in almost all regions ((S)-(-)-(18)F-fluspidine, -90%-95%; (R)-(+)
      (18)F-fluspidine, -70%-90%) whereas effects on k(4) differed according to the
      particular brain region. V(T) estimated by both graphical analysis using Logan
      plots and full nonlinear kinetic analysis revealed significant inhibition for
      both radiotracers under blocking conditions. CONCLUSION: Both (S)-(-)- and (R)
      (+)-(18)F-fluspidine appear to be suitable for sigma1R imaging in humans. The
      different pharmacokinetics of (S)-(-)-(18)F-fluspidine and (R)-(+)-(18)F
      fluspidine may have the potential for application in the diagnostics of different
      pathologic conditions.

PMID- 25071098
TI  - 18F-FDG PET and MR imaging associations across a spectrum of pediatric brain
      tumors: a report from the pediatric brain tumor consortium.
AB  - The purpose of this study was to describe (18)F-FDG uptake across a spectrum of
      pediatric brain tumors and correlate (18)F-FDG PET with MR imaging variables,
      progression-free survival (PFS), and overall survival (OS). METHODS: A
      retrospective analysis was conducted of children enrolled in phase I/II clinical
      trials through the Pediatric Brain Tumor Consortium from August 2000 to June
      2010. PET variables were summarized within diagnostic categories using
      descriptive statistics. Associations of PET with MR imaging variables and PFS and
      OS by tumor types were evaluated. RESULTS: Baseline (18)F-FDG PET was available
      in 203 children; 66 had newly diagnosed brain tumors, and 137 had
      recurrent/refractory brain tumors before enrolling in a Pediatric Brain Tumor
      Consortium trial. MR imaging was performed within 2 wk of PET and before therapy
      in all cases. The (18)F-FDG uptake pattern and MR imaging contrast enhancement
      (CE) varied by tumor type. On average, glioblastoma multiforme and
      medulloblastoma had uniform, intense uptake throughout the tumor, whereas brain
      stem gliomas (BSGs) had low uptake in less than 50% of the tumor and ependymoma
      had low uptake throughout the tumor. For newly diagnosed BSG, correlation of
      (18)F-FDG uptake with CE portended reduced OS (P = 0.032); in
      refractory/recurrent BSG, lack of correlation between (18)F-FDG uptake and CE
      suggested decreased PFS (P = 0.023). In newly diagnosed BSG for which more than
      50% of the tumor had (18)F-FDG uptake, there was a suggestion of lower apparent
      diffusion coefficient (P = 0.061) and decreased PFS (P = 0.065). CONCLUSION:
      (18)F-FDG PET and MR imaging showed a spectrum of patterns depending on tumor
      type. In newly diagnosed BSG, the correlation of (18)F-FDG uptake and CE
      suggested decreased OS, likely related to more aggressive disease. When more than
      50% of the tumor had (18)F-FDG uptake, the apparent diffusion coefficient was
      lower, consistent with increased cellularity. In refractory/recurrent BSG, poor
      correlation between (18)F-FDG uptake and CE was associated with decreased PFS,
      which may reflect concurrent tissue breakdown at sites of treated disease and
      development of new sites of (18)F-FDG-avid malignancy.

PMID- 25071100
TI  - Optimal management of esophageal adenocarcinoma: should we be CROSS?

PMID- 25071099
TI  - Cancer survivorship issues: life after treatment and implications for an aging
      population.
AB  - The US population of cancer survivors age >= 65 years will continue to grow
      rapidly over the next few decades. This growth will be driven largely by the
      aging of the national population. With the diffusion of earlier detection and
      more effective therapies, the majority of these individuals can expect to live
      long term after diagnosis. This often vulnerable group of survivors poses
      significant challenges for both researchers and clinicians with regard to how
      best to document and address its unique health care needs. In this article, we
      briefly review the long-term and late-occurring effects of cancer and its
      treatment in older survivors, review information on current patterns of post
      treatment care and the evolving guidelines for this care, and discuss
      opportunities for future research. 

PMID- 25071101
TI  - Non-small-cell lung cancer in elderly patients: a discussion of treatment
      options.
AB  - Lung cancer is a disease of the elderly. In older patients, the management of a
      malignancy as complex and potentially as lethal as lung cancer is challenging.
      Despite the fact that a large proportion of patients with non-small-cell lung
      cancer are elderly, information remains scant on how best to treat these
      patients. The goal of this review is to discuss the published literature and to
      provide guidance on how to treat elderly patients within three broad stages: (1)
      metastatic cancer, (2) early-stage cancer after surgery, and (3) locally advanced
      inoperable cancer. Because decisions on how and when to prescribe systemic
      treatment can be particularly difficult, this review focuses heavily on
      chemotherapy-related treatment decisions with some discussion of emerging data on
      the use of the comprehensive geriatric assessment.

PMID- 25071102
TI  - Reply to E. C. Smyth et al.

PMID- 25071103
TI  - PIK3CA activating mutations: a discordant role in early versus advanced hormone
      dependent estrogen receptor-positive breast cancer?

PMID- 25071104
TI  - Tumor stage after neoadjuvant chemotherapy determines survival after surgery for
      adenocarcinoma of the esophagus and esophagogastric junction.
AB  - PURPOSE: Neoadjuvant chemotherapy is established in the management of most
      resectable esophageal and esophagogastric junction adenocarcinomas. However,
      assessing the downstaging effects of chemotherapy and predicting response to
      treatment remain challenging, and the relative importance of tumor stage before
      and after chemotherapy is debatable. METHODS: We analyzed consecutive resections
      for esophageal or esophagogastric junction adenocarcinomas performed at two high
      volume cancer centers in London between 2000 and 2010. After standard
      investigations and multidisciplinary team consensus, all patients were allocated
      a clinical tumor stage before treatment, which was compared with pathologic stage
      after surgical resection. Survival analysis was conducted using Kaplan-Meier
      analysis and Cox regression analysis. RESULTS: Among 584 included patients, 400
      patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors
      after neoadjuvant chemotherapy experienced improved survival compared with
      patients without response (P < .001), and such downstaging (hazard ratio, 0.43;
      95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after
      adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular
      invasion, resection margin status, and surgical resection type. Patients
      downstaged by chemotherapy, compared with patients with no response, experienced
      lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic
      recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor
      regression scores (P = .001). Survival was strongly dictated by stage after
      neoadjuvant chemotherapy, rather than clinical stage at presentation. CONCLUSION:
      The stage of esophageal or esophagogastric junction adenocarcinoma after
      neoadjuvant chemotherapy determines prognosis rather than the clinical stage
      before neoadjuvant chemotherapy, indicating the importance of focusing on
      postchemotherapy staging to more accurately predict outcome and eligibility for
      surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from
      reduced rates of local and systemic recurrence.

PMID- 25071105
TI  - Reply to G. Procopio et al.

PMID- 25071106
TI  - Reply to D.M. Hyman et al and M. Voskoboynik et al.

PMID- 25071107
TI  - Musculoskeletal pain in patients with chronic myeloid leukemia after
      discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome?

PMID- 25071108
TI  - In vivo treatment sensitivity testing with positron emission tomography/computed
      tomography after one cycle of chemotherapy for Hodgkin lymphoma.
AB  - PURPOSE: Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography
      (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a
      favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative
      predictive value would be even higher in patients responding rapidly enough to be
      PET negative after one cycle. This prospective study aimed to assess the
      prognostic value of PET after one cycle of chemotherapy in HL and to assess the
      dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2).
      PATIENTS AND METHODS: All PET scans were read by two blinded, independent
      reviewers in different countries, according to the Deauville five-point scale.
      The main end point was progression-free survival (PFS) after 2 years. RESULTS: A
      total of 126 patients were included, and all had PET1; 89 patients had both PET1
      and PET2. The prognostic value of PET1 was statistically significant with respect
      to both PFS and overall survival. Two-year PFS for PET1-negative and PET1
      positive patients was 94.1% and 40.8%, respectively. Among those with both PET1
      and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive
      patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients,
      respectively. No PET1-negative patient was PET2 positive. CONCLUSION: PET after
      one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool
      identifies a group of patients with HL with a more favorable outcome than those
      patients with a negative PET1. In the absence of precise pretherapeutic
      predictive markers, PET1 is the best method for response-adapted strategies
      designed to select patients for less intensive treatment.

PMID- 25071109
TI  - Prevalence and clinical outcomes for patients with ALK-positive resected stage I
      to III adenocarcinoma: results from the European Thoracic Oncology Platform
      Lungscape Project.
AB  - PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK
      positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by
      population examined and detection method used. The Lungscape ALK project was
      designed to address the prevalence and prognostic impact of ALK positivity in
      resected lung adenocarcinoma in a primarily European population. METHODS:
      Analysis of ALK status was performed by immunohistochemistry (IHC) and
      fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients
      with adenocarcinoma in the European Thoracic Oncology Platform Lungscape
      iBiobank. Positive patients were matched with negative patients in a 1:2 ratio,
      both for IHC and for FISH testing. Testing was performed in 16 participating
      centers, using the same protocol after passing external quality assessment.
      RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of
      6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive,
      corresponding to a lower bound for the prevalence of FISH positivity of 2.2%.
      FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to
      46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+
      patients. The hazard of death for FISH-positive patients was lower than for IHC
      negative patients (P = .022). Multivariable models, adjusted for patient, tumor,
      and treatment characteristics, and matched cohort analysis confirmed that ALK
      FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In
      this large cohort of surgically resected lung adenocarcinomas, the prevalence of
      ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening
      strategy based on IHC or H-score could be envisaged. ALK positivity (by either
      IHC or FISH) was related to better OS.

PMID- 25071110
TI  - Emergence of new ALK mutations at relapse of neuroblastoma.
AB  - PURPOSE: In neuroblastoma, the ALK receptor tyrosine kinase is activated by point
      mutations. We investigated the potential role of ALK mutations in neuroblastoma
      clonal evolution. METHODS: We analyzed ALK mutations in 54 paired diagnosis
      relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was
      observed in one paired sample, a minor mutated component in the other sample was
      searched for by more than 100,000* deep sequencing of the relevant hotspot, with
      a sensitivity of 0.17%. RESULTS: All nine ALK-mutated cases at diagnosis
      demonstrated the same mutation at relapse, in one case in only one of several
      relapse nodules. In five additional cases, the mutation seemed to be relapse
      specific, four of which were investigated by deep sequencing. In two cases, no
      mutation evidence was observed at diagnosis. In one case, the mutation was
      present at a subclonal level (0.798%) at diagnosis, whereas in another case, two
      different mutations resulting in identical amino acid changes were detected, one
      only at diagnosis and the other only at relapse. Further evidence of clonal
      evolution of ALK-mutated cells was provided by establishment of a fully ALK
      mutated cell line from a primary sample with an ALK-mutated cell population at
      subclonal level (6.6%). CONCLUSION: In neuroblastoma, subclonal ALK mutations can
      be present at diagnosis with subsequent clonal expansion at relapse. Given the
      potential of ALK-targeted therapy, the significant spatiotemporal variation of
      ALK mutations is of utmost importance, highlighting the potential of deep
      sequencing for detection of subclonal mutations with a sensitivity 100-fold that
      of Sanger sequencing and the importance of serial samplings for therapeutic
      decisions.

PMID- 25071112
TI  - Supportive care considerations for older adults with cancer.
AB  - The treatment of cancer presents specific concerns that are unique to the growing
      demographic of elderly patients. Because the incidence of cancer is strongly
      correlated with aging, the expansion of supportive care and other age-appropriate
      therapies will be of great importance as the population of elderly patients with
      cancer increases in the coming years. Elderly patients are especially likely to
      experience febrile neutropenia, complications from chemotherapy-induced nausea,
      anemia, osteoporosis (especially in patients diagnosed with breast or prostate
      cancer), depression, insomnia, and fatigue. These issues are often complicated by
      other chronic conditions related to age, such as diabetes and cardiac disease.
      For many patients, symptoms may be addressed both through lifestyle management
      and pharmaceutical approaches. Therefore, the key to improving quality of life
      for the elderly patient with cancer is an awareness of their specific needs and a
      familiarity with emergent treatment options. 

PMID- 25071111
TI  - Can patient navigation improve receipt of recommended breast cancer care?
      Evidence from the National Patient Navigation Research Program.
AB  - PURPOSE: Poor and underserved women face barriers in receiving timely and
      appropriate breast cancer care. Patient navigators help individuals overcome
      these barriers, but little is known about whether patient navigation improves
      quality of care. The purpose of this study is to examine whether navigated women
      with breast cancer are more likely to receive recommended standard breast cancer
      care. PATIENTS AND METHODS: Women with breast cancer who participated in the
      national Patient Navigation Research Program were examined to determine whether
      the care they received included the following: initiation of antiestrogen therapy
      in patients with hormone receptor-positive breast cancer; initiation of
      postlumpectomy radiation therapy; and initiation of chemotherapy in women younger
      than age 70 years with triple-negative tumors more than 1 cm. This is a secondary
      analysis of a multicenter quasi-experimental study funded by the National Cancer
      Institute to evaluate patient navigation. Multiple logistic regression was
      performed to compare differences in receipt of care between navigated and non
      navigated participants. RESULTS: Among participants eligible for antiestrogen
      therapy, navigated participants (n = 380) had a statistically significant higher
      likelihood of receiving antiestrogen therapy compared with non-navigated controls
      (n = 381; odds ratio [OR], 1.73; P = .004) in a multivariable analysis. Among the
      participants eligible for radiation therapy after lumpectomy, navigated
      participants (n = 255) were no more likely to receive radiation (OR, 1.42; P =
      .22) than control participants (n = 297). CONCLUSION: We demonstrate that
      navigated participants were more likely than non-navigated participants to
      receive antiestrogen therapy. Future studies are required to determine the full
      impact patient navigation may have on ensuring that vulnerable populations
      receive quality care.

PMID- 25071113
TI  - Targeted therapy in older patients with solid tumors.
AB  - The introduction of targeted therapy has ushered in the era of personalized
      medicine in cancer therapy. The increased understanding of tumor heterogeneity
      has led to the determination of specific targets that can be exploited in
      treatment. This review highlights approved drugs in different therapeutic
      classes, including tyrosine kinase inhibitors, mammalian target of rapamycin
      inhibitors, drugs targeted to the human epidermal growth factor receptor 2, BRAF
      mutation targeted drugs, anti-epidermal growth factor receptor inhibitors, and
      anti-vascular endothelial growth factor therapy. There have not been elderly
      patient-specific trials of these therapies. Most of the data are extrapolated
      from larger trials in which older patients generally were a fraction of the
      participants. Therapeutic recommendations are made on the basis of this analysis
      with the recognition that the older clinical trial participants may not be
      representative of patients seen in daily practice. Patient selection and
      geriatric evaluation are critical for appropriate drug selection, dosing, and
      monitoring. With care, these therapies are a major step forward in the safe and
      effective treatment of older patients with cancer. 

PMID- 25071115
TI  - Host antitumor immunity plays a role in the survival of patients with newly
      diagnosed triple-negative breast cancer.

PMID- 25071114
TI  - Incorporating biomarkers into cancer and aging research.
AB  - The challenge in treating the older adult with cancer is accurately accounting
      for and adapting management to the heterogeneity in health status of the
      individual patient. Many oncologists recognize that chronological age alone
      should not be the determinant when deciding on a treatment regimen. Easily
      measurable markers that provide an assessment of functional age would be ideal to
      assess frailty, which may predispose the patient to complications from cancer
      treatment, including increased toxicity, functional decline, decreased quality of
      life, and poorer survival. Several categories of potential markers, including
      chronic inflammatory markers, markers of cellular senescence, and imaging to
      assess muscle mass to detect sarcopenia, may provide insight into the likelihood
      of treatment-related complications. This article discusses candidate markers and
      strategies to evaluate these markers in cancer treatment trials, with the aim of
      developing a method to assess risk of oncologic outcomes and guide management
      decisions for both the physician and patient. 

PMID- 25071117
TI  - Reply to M. Voskoboynik et al.

PMID- 25071116
TI  - Designing therapeutic clinical trials for older and frail adults with cancer: U13
      conference recommendations.
AB  - A majority of cancer diagnoses and deaths occur in patients age >= 65 years. With
      the aging of the US population, the number of older adults with cancer will grow.
      Although the coming wave of older patients with cancer was anticipated in the
      early 1980s, when the need for more research on the cancer-aging interface was
      recognized, many knowledge gaps remain when it comes to treating older and/or
      frailer patients with cancer. Relatively little is known about the best way to
      balance the risks and benefits of existing cancer therapies in older patients;
      however, these patients continue to be underrepresented in clinical trials.
      Furthermore, the available clinical trials often do not include end points
      pertinent to the older adult population, such as preservation of function,
      cognition, and independence. As part of its ongoing effort to advance research in
      the field of geriatric oncology, the Cancer and Aging Research Group held a
      conference in November 2012 in collaboration with the National Cancer Institute,
      the National Institute on Aging, and the Alliance for Clinical Trials in
      Oncology. The goal was to develop recommendations and establish research
      guidelines for the design and implementation of therapeutic clinical trials for
      older and/or frail adults. The conference sought to identify knowledge gaps in
      cancer clinical trials for older adults and propose clinical trial designs to
      fill these gaps. The ultimate goal of this conference series is to develop
      research that will lead to evidence-based care for older and/or frail adults with
      cancer.

PMID- 25071118
TI  - Refining the chemotherapy approach for older patients with colon cancer.
AB  - Population studies support an increased incidence of most cancers among older
      adults. Colorectal cancer has high prevalence in the aging population, with a
      median age of 69 years at diagnosis and 74 years at death. The vast majority of
      patients with colon cancer (CC) will require chemotherapy treatments during their
      disease course, challenging oncologists with the task of tailoring therapy for
      older patients with CC in the face of limited evidence-based data to guide them.
      Factors such as comorbidity, performance status, cognitive function, and social
      support may affect decision making and complicate tolerance of any recommended
      therapy. In recent years, attention to the specific needs of the aging population
      with cancer has given rise to the field of geriatric oncology in general, and has
      generated an increasing fund of knowledge on which to base chemotherapy delivery
      for this specific population of patients with CC. This article will review the
      available data specifically for chemotherapy management of older patients with CC
      in the postoperative and metastatic settings.

PMID- 25071119
TI  - Reply to J. Richter et al.

PMID- 25071120
TI  - Evidence-based therapy for recurrent cervical cancer.

PMID- 25071121
TI  - Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast
      cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197
      and ECOG 1199.
AB  - PURPOSE: Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are
      associated with disease-free (DFS) and overall survival (OS) in operable triple
      negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs
      in primary TNBCs in two adjuvant phase III trials conducted by the Eastern
      Cooperative Oncology Group (ECOG). PATIENTS AND METHODS: Full-face hematoxylin
      and eosin-stained sections of 506 tumors from ECOG trials E2197 and E1199 were
      evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments
      (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based
      on availability of sections. For the primary end point of DFS, association with
      TIL scores was determined by fitting proportional hazards models stratified on
      study. Secondary end points were OS and distant recurrence-free interval (DRFI).
      Reporting recommendations for tumor marker prognostic studies criteria were
      followed, and all analyses were prespecified. RESULTS: The majority of 481
      evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of
      10.6 years, higher sTIL scores were associated with better prognosis; for every
      10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02),
      18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk
      of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an
      independent prognostic marker of DFS, DRFI, and OS. CONCLUSION: In two national
      randomized clinical trials using contemporary adjuvant chemotherapy, we confirm
      that stromal lymphocytic infiltration constitutes a robust prognostic factor in
      TNBCs. Studies assessing outcomes and therapeutic efficacies should consider
      stratification for this parameter.

PMID- 25071123
TI  - Reply to G. Mangili et al and C. Lhomme et al.

PMID- 25071122
TI  - Cardiac effects of anticancer therapy in the elderly.
AB  - Cancer incidence increases with age, and as life expectancy increases, the number
      of elderly patients with cancer is increasing. Cancer treatments, including
      chemotherapy and radiotherapy, have significant short- and long-term effects on
      cardiovascular function. These cardiotoxic effects can be acute, such as changes
      in electrocardiogram (ECG), arrhythmias, ischemia, and pericarditis and/or
      myocarditis-like syndromes, or they can be chronic, such as ventricular
      dysfunction. Anticancer therapies can also have indirect effects, such as
      alterations in blood pressure, or can cause metabolic abnormalities that
      subsequently increase risk for cardiac events. In this review, we explore both
      observational and clinical trial evidence of cardiac risk in the elderly. In both
      observational and clinical trial data, risk of cardiotoxicity with anthracycline
      based chemotherapy increases with age. However, it is less clear whether the
      association between age and cardiotoxicity exists for newer treatments. The
      association may not be well demonstrated as a result of under-representation of
      elderly patients in clinical trials and avoidance of these therapies in this
      population. In addition, we discuss strategies for surveillance and prevention of
      cardiotoxicity in the elderly. In the elderly, it is important to be aware of the
      potential for cardiotoxicity during long-term follow-up and to consider both
      prevention and surveillance of these late effects. 

PMID- 25071124
TI  - Surgical considerations in older adults with cancer.
AB  - PURPOSE: The aging of the population is a real concern for surgical oncologists,
      who are increasingly being asked to treat patients who would not have been
      considered for surgery in the past. In many cases, decisions are made with
      relatively little evidence, most of which was derived from trials in which older
      age was a limiting factor for recruitment. METHODS: This review focuses on risk
      assessment and perioperative management. It describes the relationship between
      age and outcomes for colon, lung, hepatobiliary, and head and neck cancer, which
      are predominantly diseases of the elderly and are a major cause of morbidity and
      mortality. RESULTS: Effective surgery requires safe performance as well as
      reasonable postoperative life expectancy and maintenance of quality of life.
      Treatment decisions for potentially vulnerable elderly patients should take into
      account data obtained from the evaluation of geriatric syndromes, such as
      frailty, functional and cognitive limitations, malnutrition, comorbidities, and
      polypharmacy, as well as social support. Postoperative care should include
      prevention and treatment of complications seen more frequently in the elderly,
      including postoperative delirium, functional decline, and the need for
      institutionalization. CONCLUSION: Surgery remains the best modality for treatment
      of solid tumors, and chronologic age alone should not be a determinant for
      treatment decisions. With adequate perioperative risk stratification, functional
      assessment, and oncologic prognostication, elderly patients with cancer can do as
      well in terms of morbidity and mortality as their younger counterparts. If
      surgery is determined to be the appropriate treatment modality, patients should
      not be denied this option because of their age.

PMID- 25071126
TI  - Biology of cancer and aging: a complex association with cellular senescence.
AB  - Over the last 50 years, major improvements have been made in our understanding of
      the driving forces, both parallel and opposing, that lead to aging and cancer.
      Many theories on aging first proposed in the 1950s, including those associated
      with telomere biology, senescence, and adult stem-cell regulation, have since
      gained support from cumulative experimental evidence. These views suggest that
      the accumulation of mutations might be a common driver of both aging and cancer.
      Moreover, some tumor suppressor pathways lead to aging in line with the theory of
      antagonist pleiotropy. According to the evolutionary-selected disposable soma
      theory, aging should affect primarily somatic cells. At the cellular level, both
      intrinsic and extrinsic pathways regulate aging and senescence. However,
      increasing lines of evidence support the hypothesis that these driving forces
      might be regulated by evolutionary-conserved pathways that modulate energy
      balance. According to the hyperfunction theory, aging is a quasi-program favoring
      both age-related diseases and cancer that could be inhibited by the regulation of
      longevity pathways. This review summarizes these hypotheses, as well as the
      experimental data that have accumulated over the last 60 years linking aging and
      cancer.

PMID- 25071127
TI  - Geriatric oncology: an overview.

PMID- 25071125
TI  - International Society of Geriatric Oncology consensus on geriatric assessment in
      older patients with cancer.
AB  - PURPOSE: To update the International Society of Geriatric Oncology (SIOG) 2005
      recommendations on geriatric assessment (GA) in older patients with cancer.
      METHODS: SIOG composed a panel with expertise in geriatric oncology to develop
      consensus statements after literature review of key evidence on the following
      topics: rationale for performing GA; findings from a GA performed in geriatric
      oncology patients; ability of GA to predict oncology treatment-related
      complications; association between GA findings and overall survival (OS); impact
      of GA findings on oncology treatment decisions; composition of a GA, including
      domains and tools; and methods for implementing GA in clinical care. RESULTS: GA
      can be valuable in oncology practice for following reasons: detection of
      impairment not identified in routine history or physical examination, ability to
      predict severe treatment-related toxicity, ability to predict OS in a variety of
      tumors and treatment settings, and ability to influence treatment choice and
      intensity. The panel recommended that the following domains be evaluated in a GA:
      functional status, comorbidity, cognition, mental health status, fatigue, social
      status and support, nutrition, and presence of geriatric syndromes. Although
      several combinations of tools and various models are available for implementation
      of GA in oncology practice, the expert panel could not endorse one over another.
      CONCLUSION: There is mounting data regarding the utility of GA in oncology
      practice; however, additional research is needed to continue to strengthen the
      evidence base.

PMID- 25071128
TI  - Surveillance policy for stage IA malignant ovarian germ cell tumors in children
      and young adults.

PMID- 25071129
TI  - Breast and ovarian cancer in the older woman.
AB  - Nearly half of all women diagnosed with breast or ovarian cancer are age 65 years
      or older with the number of women diagnosed expected to increase as the
      population ages and life expectancy improves. Older women are less likely to be
      offered standard cancer treatments, are more likely to develop higher toxicity,
      and have higher mortality. Chronologic age should not be the only factor used for
      making treatment decisions. Functional dependence, organ function, comorbidity,
      polypharmacy, social support, cognitive and/or psychosocial factors, overall life
      expectancy, and patient's goals of care are equally vital and should be assessed
      before and during treatment. In this review, current evidence and treatment
      guidelines for older women with breast or ovarian cancer are outlined.

PMID- 25071130
TI  - Adjuvant chemotherapy in stage I ovarian germ cell tumors: should indications and
      treatment modalities be different in young girls and adults?

PMID- 25071131
TI  - Reply to E. C. Smyth et al.

PMID- 25071132
TI  - Radiation treatment in older patients: a framework for clinical decision making.
AB  - In older patients, radiation treatment plays a vital role in curative and
      palliative cancer therapy. Radiation treatment recommendations should be informed
      by a comprehensive, personalized risk-benefit assessment that evaluates treatment
      efficacy and toxicity. We review several clinical factors that distinctly affect
      efficacy and toxicity of radiation treatment in older patients. First,
      locoregional tumor behavior may be more indolent in older patients for some
      disease sites but more aggressive for other sites. Assessment of expected
      locoregional relapse risk informs the magnitude and timeframe of expected
      radiation treatment benefits. Second, assessment of the competing cancer versus
      noncancer mortality and morbidity risks contextualizes cancer treatment
      priorities holistically within patients' entire spectrum and time course of
      health needs. Third, assessment of functional reserve helps predict patients'
      acute treatment tolerance, differentiating those patients who are unlikely to
      benefit from treatment or who are at high risk for treatment complications.
      Potential radiation treatment options include immediate curative treatment,
      delayed curative treatment, and no treatment, with additional consideration given
      to altered radiation target, dose, or sequencing with chemotherapy and/or
      surgery. Finally, when cure is not feasible, palliative radiation therapy remains
      valuable for managing symptoms and achieving meaningful quality-of-life
      improvements. Our proposed decision-making framework integrates these factors to
      help radiation oncologists formulate strategic treatment recommendations within a
      multidisciplinary context. Future research is still needed to identify how
      advanced technologies can be judiciously applied in curative and palliative
      settings to enhance risk-benefit profiles of radiation treatment in older
      patients and more accurately quantify treatment efficacy in this group. 

PMID- 25071134
TI  - Personalizing medicine in geriatric oncology.
AB  - Minimizing toxicity while maximizing efficacy is a common goal in the treatment
      of any condition but its importance is underscored in the discipline of oncology
      because of the serious nature of many chemotherapeutic toxicities and the risk of
      cancer recurrence or disease progression. The challenge of achieving an optimal
      therapeutic index is especially augmented in the elderly population because of
      age-related metabolism changes and interacting concurrent medications. Additional
      factors, such as germline mutations in drug-metabolizing enzymes and other
      pharmacogenomic alterations, may have more pronounced effects in elderly
      patients, given their predisposition to altered pharmacokinetics and
      pharmacodynamics with resulting increased risk of toxicity. Examples of the
      possible interplay of these factors will be discussed using tamoxifen,
      paclitaxel, codeine, and fluorouracil as starting points. Limited participation
      of the elderly in many cancer trials, especially trials assessing drug exposure,
      makes much knowledge on the interaction of these patient and environmental
      factors speculative in nature but presents an opportunity for future research to
      achieve better optimization of chemotherapeutic agents in the elderly.

PMID- 25071133
TI  - Pemetrexed and cisplatin for the treatment of advanced, persistent, or recurrent
      carcinoma of the cervix: a limited access phase II trial of the gynecologic
      oncology group.
AB  - PURPOSE: To estimate the antitumor activity of pemetrexed and cisplatin with
      objective tumor response (partial and complete) in patients with advanced,
      persistent, or recurrent carcinoma of the cervix and to determine the nature and
      degree of toxicity of this regimen. Secondarily, this study will determine the
      effects of this regimen on progression-free survival and overall survival.
      PATIENTS AND METHODS: Eligible, consenting patients received pemetrexed 500
      mg/m(2) and cisplatin 50 mg/m(2) intravenously repeated every 21 days until
      disease progression or adverse events prohibited further therapy. Patients
      received no prior therapeutic chemotherapy, except when administered concurrently
      with primary radiation therapy. Subsequent doses were adjusted according to
      observed toxicity and protocol guidelines. Adverse events were assessed with
      Common Terminology Criteria for Adverse Events v 3.0. The primary measure of
      efficacy was tumor response according to Response Evaluation Criteria in Solid
      Tumors. The study was stratified by prior radiation therapy. RESULTS: From
      September 2008 to November 2011, 55 patients were enrolled by five Gynecologic
      Oncology Group member institutions; of those, 54 patients were eligible and
      assessable. The regimen was well tolerated with 26% receiving more than nine
      cycles. The most common greater than grade 2 toxicities were neutropenia 35%,
      leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one
      complete and 16 partial). The median progression-free survival was 5.7 months,
      and overall survival was 12.3 months. CONCLUSION: Pemetrexed in combination with
      cisplatin demonstrates activity in the treatment of advanced, persistent, or
      recurrent carcinoma of the cervix.

PMID- 25071136
TI  - Concurrent Disseminated Nocardiosis and GI Mucormycosis in a Stem-Cell
      Transplantation Recipient.

PMID- 25071135
TI  - Cognitive effects of cancer systemic therapy: implications for the care of older
      patients and survivors.
AB  - The number of patients with cancer who are age 65 years or older (hereinafter
      "older") is increasing dramatically. One obvious aspect of cancer care for this
      group is that they are experiencing age-related changes in multiple organ
      systems, including the brain, which complicates decisions about systemic therapy
      and assessments of survivorship outcomes. There is a consistent body of evidence
      from studies that use neuropsychological testing and neuroimaging that supports
      the existence of impairment following systemic therapy in selected cognitive
      domains among some older patients with cancer. Impairment in one or more
      cognitive domains could have important effects in the daily lives of older
      patients. However, an imperfect understanding of the precise biologic mechanisms
      underlying cognitive impairment after systemic treatment precludes development of
      validated methods for predicting which older patients are at risk. From what is
      known, risks may include lifestyle factors such as smoking, genetic
      predisposition, and specific comorbidities such as diabetes and cardiovascular
      disease. Risk also interacts with physiologic and cognitive reserve, because even
      at the same chronological age and with the same number of illnesses, older
      patients vary from having high reserve (ie, biologically younger than their age)
      to being frail (biologically older than their age). Surveillance for the presence
      of cognitive impairment is also an important component of long-term survivorship
      care with older patients. Increasing the workforce of cancer care providers who
      have geriatrics training or who are working within multidisciplinary teams that
      have this type of expertise would be one avenue toward integrating assessment of
      the cognitive effects of cancer systemic therapy into routine clinical practice. 

PMID- 25071137
TI  - Prostate cancer in the elderly patient.
AB  - Treatment for prostate cancer (PCa) has evolved significantly over the last
      decade. PCa is the most prevalent non-skin cancer and the second leading cause of
      cancer death in men, and it has an increased incidence and prevalence in older
      men. As a result, physicians and patients are faced with the challenge of
      identifying optimal treatment strategies for localized, biochemical recurrent,
      and advanced PCa in the older population. When older patients are appropriately
      selected, treatment for PCa results in survival benefits and toxicity profiles
      similar to those experienced in younger patients. However, underlying health
      status and age-related changes can have an impact on tolerance of hormonal
      therapy and chemotherapy in men with advanced disease. Therefore, the
      heterogeneity of the elderly population necessitates a multidimensional
      assessment to maximize the benefit of medical and/or surgical options. Providing
      clinicians with the requisite health status data on which to base treatment
      decisions would help ensure that older patients with PCa receive optimal therapy
      if it will benefit them and/or active surveillance or best supportive care if it
      will not. We provide a review of the existing evidence to date on the management
      of PCa in the older population.

PMID- 25071139
TI  - Liver Failure After Abdominal Irradiation: Identifying the Right Suspects.

PMID- 25071138
TI  - Acute myeloid leukemia and myelodysplastic syndromes in older adults.
AB  - Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic
      syndromes (MDS) is challenging because of disease morbidity and associated
      treatments. Both diseases represent a genetically heterogeneous group of
      disorders primarily affecting older adults, with treatment strategies ranging
      from supportive care to hematopoietic stem-cell transplantation. Although
      selected older adults can benefit from intensive therapies, as a group they
      experience increased treatment-related morbidity, are more likely to relapse, and
      have decreased survival. Age-related outcome disparities are attributed to both
      tumor and patient characteristics, requiring an individualized approach to
      treatment decision making beyond consideration of chronologic age alone.
      Selection of therapy for any individual requires consideration of both disease
      specific risk factors and estimates of treatment tolerance and life expectancy
      derived from evaluation of functional status and comorbidity. Although treatment
      options for older adults are expanding, clinical trials accounting for the
      heterogeneity of tumor biology and aging are needed to define standard-of-care
      treatments for both disease groups. In addition, trials should include outcomes
      addressing quality of life, maintenance of independence, and use of health care
      services to assist in patient-centered decision making. This review will
      highlight available evidence in treatment of older adults with AML or MDS and
      unanswered clinical questions for older adults with these diseases.

PMID- 25071140
TI  - Butterfly and renal cell cancer: out of chaos comes order.

PMID- 25071141
TI  - Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane
      adjuvant multinational pathology study.
AB  - PURPOSE: Deregulation of key PI3K/AKT pathway genes may contribute to endocrine
      resistance in breast cancer (BC). PIK3CA is the most frequently mutated gene in
      luminal BC (35%); however, the effect of mutations in helical versus kinase
      domains remains controversial. We hypothesize that improved outcomes occur in
      patients with estrogen receptor-positive (ER positive) BC receiving endocrine
      therapy and possessing PIK3CA mutations. MATERIALS AND METHODS: DNA was extracted
      from 4,540 formalin-fixed paraffin-embedded BC samples from the Exemestane Versus
      Tamoxifen-Exemestane pathology study. Mutational analyses were performed for 25
      mutations (PIK3CAx10, AKT1x1, KRASx5, HRASx3, NRASx2 and BRAFx4). RESULTS: PIK3CA
      mutations were frequent (39.8%), whereas RAS/RAF mutations were rare (1%). In
      univariable analyses PIK3CA mutations were associated with significantly improved
      5-year distant relapse-free survival (DRFS; HR, 0.76; 95% CI, 0.63 to 0.91; P =
      .003). However, a multivariable analysis correcting for known clinical and
      biologic prognostic factors failed to demonstrate that PIK3CA mutation status is
      an independent prognostic marker for DRFS (HR, 0.92; 95% CI, 0.75 to 1.12; P =
      .4012). PIK3CA mutations were more frequent in low-risk luminal BCs (e.g., grade
      1 nodev 3, node-negative v -positive), confounding the relationship between
      mutations and outcome. CONCLUSION: PIK3CA mutations are present in approximately
      40% of luminal BCs but are not an independent predictor of outcome in the context
      of endocrine therapy, whereas RAS/RAF mutations are rare inluminal BC. A complex
      relationship between low-risk cancers and PIK3CA mutations was identified.
      Although the PI3K/AKT pathway remains a viable therapeutic target as the result
      of ahigh mutation frequency, PIK3CA mutations do not seem to affect residual risk
      following treatment with endocrine therapy.

PMID- 25071142
TI  - Improving patient selection for phase I oncology trials.

PMID- 25071143
TI  - Multiple myeloma in the older adult: better prospects, more challenges.
AB  - PURPOSE: Multiple myeloma (MM) is disproportionately diagnosed in older adults;
      with the aging of the population, the number of older adults diagnosed with MM
      will increase by nearly 80% in the next two decades. Duration of survival has
      improved dramatically over the last 20 years, but the improvements in older
      adults have not been as great as those in younger adults with MM. METHODS: In
      this article, we address treatment approaches in older adults who are eligible
      for and those ineligible for high-dose therapy with autologous stem-cell
      transplantation as well as supportive care considerations and the potential role
      for geriatric assessment in facilitating decision making for older adults with
      MM. RESULTS: The evidence from recent studies demonstrates that combinations of
      novel and conventional antimyeloma agents result in improved response rates and,
      in some cases, improved progression-free and overall survival. However, some
      older adults are particularly vulnerable to toxicities of therapy and
      discontinuation of therapy and, consequently, they have poorer survival. In
      addition, older adults may prioritize other outcomes of therapy, such as quality
      of life, over more conventional end points such as disease response and duration
      of survival. Geriatric assessment can facilitate risk-stratification of older
      adults at greater risk for adverse events from therapy and aid in personalizing
      therapy for vulnerable or frail older adults. CONCLUSION: Survival in older
      adults with MM is improving with novel therapeutics, but efficacy must be
      balanced with risk of toxicity of therapy and maintenance of quality of life.
      Novel instruments such as geriatric assessment tools may facilitate these aims.

PMID- 25071144
TI  - Celebrating our best.

PMID- 25071146
TI  - Extending oral health care services to underserved children through a school
      based collaboration: Part 3--A cost analysis.
AB  - PURPOSE: The purpose of this manuscript was to conduct a cost analysis of the
      Miles of Smiles Program, a collaboration between the University of Missouri
      Kansas City School of Dentistry and the Olathe School District in Kansas. This
      preventive program was implemented to improve the access to oral health care for
      low income children within the school district. METHODS: An inventory list and de
      identified patient records were used to determine the costs associated with
      operating the program to serve 339 elementary school students during the 2008 to
      2009 school term. Costs related to equipment, supplies and personnel were
      included. The costs were then compared to the amount of Medicaid reimbursement
      obtained for the services provided. Additionally, the cost of operating a similar
      program, if staffed by dental professionals rather than supervised dental hygiene
      students, was estimated. RESULTS: The cost of operating the program during the
      2008 to 2009 school term was $107,515.74. The program received Medicaid
      reimbursement for approximately 1.5% of the total operating cost of and
      approximately 6.3% of the total billable services, however, challenges with
      submitting and billing Medicaid claims for the first time contributed to this low
      rate of reimbursement. If a similar program that utilized dental professionals
      was implemented and treated the same number of patients, the cost would be
      approximately $37,529.65 more due to higher expenses associated with personnel
      and supplies. CONCLUSION: The program is not self-sustainable based on Medicaid
      government-funded insurance reimbursement alone, and therefore continuous
      external sources of funding or a change in the program design would be necessary
      for long-term sustainability of the program.

PMID- 25071145
TI  - Chronic HPA axis response to stress in temporomandibular disorder.
AB  - PURPOSE: Perceived stress is associated with temporomandibular disorder (TMD),
      but whether cortisol levels are elevated in individuals with TMD is unknown. We
      hypothesized that cortisol concentration, a biomarker of hypothalamic-pituitary
      adrenal (HPA) axis function, was elevated in TMD cases relative to controls, and
      that perceived stress was positively correlated with cortisol concentration.
      METHODS: In this case control study, TMD case status was determined by examiners
      using TMD Research Diagnostic Criteria. Participants (n=116) aged 18 to 59 years
      were recruited from within a 50 mile radius of the University of North Carolina
      at Chapel Hill. Following examination, cases (n=45) and controls (n=71) completed
      the 14-item Perceived Stress Scale using a reference interval of the past 3
      months. Approximately 100 strands of hair were cut from the posterior vertex
      segment of their scalp. The 3 centimeters of hair most proximal to the scalp was
      analyzed with a commercially available salivary cortisol enzyme immunoassay
      adapted for hair cortisol. This length corresponds to the last 3 months of
      systemic HPA axis activity. RESULTS: TMD cases perceived higher stress than
      controls (p=0.001). However, hair cortisol concentration was lower in TMD cases
      than controls (p<0.001). The correlation coefficient revealed a weak negative
      relationship (r=-0.188) between perceived stress and hair cortisol concentration
      (p=0.044). In analysis stratified by case status, the relationship of perceived
      stress and hair cortisol concentration was non-significant for cases (p=0.169)
      and controls (p=0.498). CONCLUSION: Despite greater perceived stress, TMD cases
      had lower hair cortisol concentrations than controls and the 2 measures of stress
      were weakly and negatively correlated.

PMID- 25071147
TI  - Short-term effects of non-surgical periodontal therapy on clinical measures of
      impaired glucose tolerance in people with prediabetes and chronic periodontitis.
AB  - PURPOSE: Diabetes and periodontal disease are conditions considered to be
      biologically linked. Prediabetes is a condition in which individuals have blood
      glucose levels, impaired fasting glucose (IFG) and/or impaired glucose tolerance
      (IGT) or glycated hemoglobin (A1C) levels higher than normal but not high enough
      to be classified as diabetes. Few human studies address the relationship between
      periodontitis and prediabetes or clarify an association between periodontitis and
      prediabetes. The purpose of this pilot study was to examine the impact of non
      surgical periodontal therapy (NSPT) on clinical measures of glycemic control in
      prediabetes. METHODS: Prediabetes measures of IFG, IGT, A1C and periodontal
      measures of pocket depth (PD), clinical attachment level (CAL), plaque index (PI)
      and gingival index (GI) were taken at baseline and 3 months in 12 subjects with
      prediabetes and chronic slight to moderate periodontitis. Blood samples were
      taken from each subject following an 8 hour fast. This study controlled for
      changes in medications, body-mass index, physical activity and diet. RESULTS:
      Comparison of mean prediabetes and periodontal measures from baseline and post
      treatment at 3 months demonstrated clinical improvement for both periodontal and
      prediabetes measures. A mean reduction in PD of 0.27 (p=0.003), CAL of 0.32
      (p=0.050) and A1C of 0.19 (p=0.015) reached statistical significance. CONCLUSION:
      This pilot study suggests NSPT improves A1C and periodontal measures at 3 months.
      The robustness of measures is limited due to the small sample size and lack of a
      control group. Further larger scale studies using a randomized control design
      would be informative.

PMID- 25071148
TI  - Assessment of women, infants and children providers' perceptions of oral health
      counseling and availability of associated resources.
AB  - PURPOSE: Children from low-income families and ethnic minority groups are
      associated with an increased risk of developing dental disease and are often
      enrolled in the Women, Infants and Children (WIC) nutritional program. It has
      been an intention of the Michigan Department of Community Health (MDCH) Oral
      Health Program (OHP) to collaborate with WIC to provide preventive oral health
      resources and education to their population. This project focused on achieving
      the goals outlined in the Michigan 2010 State Oral Health Plan. METHODS: An 18
      question survey was designed to identify gaps existing in oral health counseling
      in Michigan WIC agencies. The survey was disseminated to 56 MI WIC agencies.
      RESULTS: WIC providers perceive oral health risk assessment to be important and
      are asking oral health questions during certification and re-certification
      appointments. Seventy-nine percent of participants indicated they never had
      training in oral health counseling, and 79% are interested in learning more about
      oral health. Agencies are interested in obtaining oral health education resources
      for their clients. CONCLUSION: The 2010 State Oral Health Plan's goals recognized
      the need for oral health related resources and education within community-based
      programs like WIC. The results of the survey support the need for additional oral
      health counseling and associated resources in WIC agencies. This information will
      be used to help the MDCH OHP find ways to address these gaps.

PMID- 25071149
TI  - Early benefits with daily rinsing on gingival health improvements with an
      essential oil mouthrinse--post-hoc analysis of 5 clinical trials.
AB  - PURPOSE: The aim of this investigation through post-hoc analyses was to determine
      the ability to achieve gingival health in the short term with daily rinsing with
      an essential oil containing antimicrobial mouthrinse. METHODS: Conventional
      Analysis of Covariance (ANCOVA) on whole mouth mean plaque and gingivitis scores
      were originally conducted to demonstrate efficacy of adjunctive use of Cool
      Mint(r) LISTERINE(r) Antiseptic (EO) compared to negative control [brushing (B)
      or brushing/flossing (BF)] in each of 5 studies containing a 4 week evaluation.
      The Modified Gingival Index (MGI) was split into 2 categories: healthy (scores 0,
      1) and unhealthy (>=2). Data, reflecting subjects that completed 4 weeks of
      treatment from 5 studies, were evaluated to determine the mean percent of healthy
      sites and mean percent of more inflamed "affected" areas (MGI>=3). RESULTS: At
      baseline, the mean percent healthy gingival sites ranged from 0.1 to 3.2%. At 4
      weeks, up to 29.3% and 16.1% of sites were healthy for the EO group and negative
      control group, respectively. Three and 6 month data from 2 of the 5 studies
      resulted in up to 39.6% and 62% at 3 and 6 month mean percent healthy sites per
      subject for EO and up to 17.2% and 15.6% at 3 and 6 months, respectively, for
      negative control. Virtually plaque free sites (PI=0, 1) at 4 weeks ranged up to
      34.3% and 8.1% for EO and control groups, respectively. CONCLUSION: Significantly
      more healthy gingival sites and virtually plaque free tooth surfaces can be
      achieved as early as 4 weeks with use of an essential oil antimicrobial
      mouthrinse. This finding continues through 6 months twice daily use as part of
      oral care practices compared to mechanical oral hygiene alone.

PMID- 25071150
TI  - The hypoxia-inducible epigenetic regulators Jmjd1a and G9a provide a mechanistic
      link between angiogenesis and tumor growth.
AB  - Hypoxia promotes stem cell maintenance and tumor progression, but it remains
      unclear how it regulates long-term adaptation toward these processes. We reveal a
      striking downregulation of the hypoxia-inducible histone H3 lysine 9 (H3K9)
      demethylase JMJD1A as a hallmark of clinical human germ cell-derived tumors, such
      as seminomas, yolk sac tumors, and embryonal carcinomas. Jmjd1a was not essential
      for stem cell self-renewal but played a crucial role as a tumor suppressor in
      opposition to the hypoxia-regulated oncogenic H3K9 methyltransferase G9a.
      Importantly, loss of Jmjd1a resulted in increased tumor growth, whereas loss of
      G9a produced smaller tumors. Pharmacological inhibition of G9a also resulted in
      attenuation of tumor growth, offering a novel therapeutic strategy for germ cell
      derived tumors. Finally, Jmjd1a and G9a drive mutually opposing expression of the
      antiangiogenic factor genes Robo4, Igfbp4, Notch4, and Tfpi accompanied by
      changes in H3K9 methylation status. Thus, we demonstrate a novel mechanistic link
      whereby hypoxia-regulated epigenetic changes are instrumental for the control of
      tumor growth through coordinated dysregulation of antiangiogenic gene expression.

PMID- 25071151
TI  - 12-lipoxygenase promotes obesity-induced oxidative stress in pancreatic islets.
AB  - High-fat diets lead to obesity, inflammation, and dysglycemia. 12-Lipoxygenase
      (12-LO) is activated by high-fat diets and catalyzes the oxygenation of cellular
      arachidonic acid to form proinflammatory intermediates. We hypothesized that 12
      LO in the pancreatic islet is sufficient to cause dysglycemia in the setting of
      high-fat feeding. To test this, we generated pancreas-specific 12-LO knockout
      mice and studied their metabolic and molecular adaptations to high-fat diets.
      Whereas knockout mice and control littermates displayed identical weight gain,
      body fat distribution, and macrophage infiltration into fat, knockout mice
      exhibited greater adaptive islet hyperplasia, improved insulin secretion, and
      complete protection from dysglycemia. At the molecular level, 12-LO deletion
      resulted in increases in islet antioxidant enzymes Sod1 and Gpx1 in response to
      high-fat feeding. The absence or inhibition of 12-LO led to increases in nuclear
      Nrf2, a transcription factor responsible for activation of genes encoding
      antioxidant enzymes. Our data reveal a novel pathway in which islet 12-LO
      suppresses antioxidant enzymes and prevents the adaptive islet responses in the
      setting of high-fat diets. 

PMID- 25071152
TI  - p66ShcA promotes breast cancer plasticity by inducing an epithelial-to
      mesenchymal transition.
AB  - Breast cancers are stratified into distinct subtypes, which influence therapeutic
      responsiveness and patient outcome. Patients with luminal breast cancers are
      often associated with a better prognosis relative to that with other subtypes.
      However, subsets of patients with luminal disease remain at increased risk of
      cancer-related death. A critical process that increases the malignant potential
      of breast cancers is the epithelial-to-mesenchymal transition (EMT). The p66ShcA
      adaptor protein stimulates the formation of reactive oxygen species in response
      to stress stimuli. In this paper, we report a novel role for p66ShcA in inducing
      an EMT in HER2(+) luminal breast cancers. p66ShcA increases the migratory
      properties of breast cancer cells and enhances signaling downstream of the Met
      receptor tyrosine kinase in these tumors. Moreover, Met activation is required
      for a p66ShcA-induced EMT in luminal breast cancer cells. Finally, elevated
      p66ShcA levels are associated with the acquisition of an EMT in primary breast
      cancers spanning all molecular subtypes, including luminal tumors. This is of
      high clinical relevance, as the luminal and HER2 subtypes together comprise 80%
      of all newly diagnosed breast cancers. This study identifies p66ShcA as one of
      the first prognostic biomarkers for the identification of more aggressive tumors
      with mesenchymal properties, regardless of molecular subtype. 

PMID- 25071153
TI  - Gcn5 and PCAF regulate PPARgamma and Prdm16 expression to facilitate brown
      adipogenesis.
AB  - The acetyltransferase Gcn5 is critical for embryogenesis and shows partial
      functional redundancy with its homolog PCAF. However, the tissue- and cell
      lineage-specific functions of Gcn5 and PCAF are still not well defined. Here we
      probe the functions of Gcn5 and PCAF in adipogenesis. We found that the double
      knockout (DKO) of Gcn5/PCAF inhibits expression of the master adipogenic
      transcription factor gene PPARgamma, thereby preventing adipocyte
      differentiation. The adipogenesis defects in Gcn5/PCAF DKO cells are rescued by
      ectopic expression of peroxisome proliferator-activated receptor gamma
      (PPARgamma), suggesting Gcn5/PCAF act upstream of PPARgamma to facilitate
      adipogenesis. The requirement of Gcn5/PCAF for PPARgamma expression was
      unexpectedly bypassed by prolonged treatment with an adipogenic inducer, 3
      isobutyl-1-methylxanthine (IBMX). However, neither PPARgamma ectopic expression
      nor prolonged IBMX treatment rescued defects in Prdm16 expression in DKO cells,
      indicating that Gcn5/PCAF are essential for normal Prdm16 expression. Gcn5/PCAF
      regulate PPARgamma and Prdm16 expression at different steps in the transcription
      process, facilitating RNA polymerase II recruitment to Prdm16 and elongation of
      PPARgamma transcripts. Overall, our study reveals that Gcn5/PCAF facilitate
      adipogenesis through regulation of PPARgamma expression and regulate brown
      adipogenesis by influencing Prdm16 expression. 

PMID- 25071154
TI  - Role of UTX in retinoic acid receptor-mediated gene regulation in leukemia.
AB  - Human UTX, a member of the Jumonji C family of proteins, associates with mixed
      lineage leukemia 3/4 complexes. Stimulation with retinoic acid leads to the
      recruitment of UTX-containing complexes to HOX genes, which results in
      demethylation of histone H3 lysine 27 and concomitant methylation of histone H3
      lysine 4. Here, we show that UTX interacts with the retinoic acid receptor alpha
      (RARalpha) and that this interaction is essential for proper differentiation of
      leukemic U937 cells in response to retinoic acid. UTX occupies the promoters of
      several RAR target genes and regulates their transcriptional output by modulating
      ASH2L complex recruitment. Overexpression of UTX in promyelocytic NB4 cells
      results in enhanced cellular differentiation upon retinoic acid treatment. Our
      results show that UTX is important for RAR-mediated transcription and provide
      insight into the critical role of cross talk between histone H3 lysine 4
      methylation and histone H3 lysine 27 demethylation during cellular
      differentiation. 

PMID- 25071155
TI  - WWP2-WWP1 ubiquitin ligase complex coordinated by PPM1G maintains the balance
      between cellular p73 and DeltaNp73 levels.
AB  - The balance between transcription factor p73 and its functionally opposing N
      terminally truncated DeltaNp73 isoform is critical for cell survival, but the
      precise mechanism that regulates their levels is not clear. In our study, we
      identified WWP2, an E3 ligase, as a novel p73-associated protein that
      ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3
      ligase, WWP1, which specifically ubiquitinates and degrades DeltaNp73. Further,
      we identified phosphatase PPM1G as a functional switch that controls the balance
      between monomeric WWP2 and a WWP2/WWP1 heterodimeric state in the cell. During
      cellular stress, WWP2 is inactivated, leading to upregulation of p73, whereas
      WWP2-WWP1 complex is intact to degrade DeltaNp73, thus playing an important role
      in shifting the balance between p73 and DeltaNp73. Collectively, our results
      reveal a new functional E3 ligase complex controlled by PPM1G that differentially
      regulates cellular p73 and DeltaNp73. 

PMID- 25071156
TI  - Absence of a red blood cell phenotype in mice with hematopoietic deficiency of
      SEC23B.
AB  - Congenital dyserythropoietic anemia type II (CDAII) is an autosomal recessive
      disease of ineffective erythropoiesis characterized by increased
      bi/multinucleated erythroid precursors in the bone marrow. CDAII results from
      mutations in SEC23B. The SEC23 protein is a core component of coat protein
      complex II-coated vesicles, which transport secretory proteins from the
      endoplasmic reticulum to the Golgi apparatus. Though the genetic defect
      underlying CDAII has been identified, the pathophysiology of this disease remains
      unknown. We previously reported that SEC23B-deficient mice die perinatally,
      exhibiting massive pancreatic degeneration, with this early mortality limiting
      evaluation of the adult hematopoietic compartment. We now report that mice with
      SEC23B deficiency restricted to the hematopoietic compartment survive normally
      and do not exhibit anemia or other CDAII characteristics. We also demonstrate
      that SEC23B-deficient hematopoietic stem cells (HSC) do not exhibit a
      disadvantage at reconstituting hematopoiesis when compared directly to wild-type
      HSC in a competitive repopulation assay. Secondary bone marrow transplants
      demonstrated continued equivalence of SEC23B-deficient and WT HSC in their
      hematopoietic reconstitution potential. The surprising discordance in phenotypes
      between SEC23B-deficient mice and humans may reflect an evolutionary shift in
      SEC23 paralog function and/or expression, or a change in a specific COPII cargo
      critical for erythropoiesis. 

PMID- 25071158
TI  - Detection of bla(NDM-4) in Escherichia coli from hospital sewage.

PMID- 25071157
TI  - Identification of distinct glycoforms of IgA1 in plasma from patients with
      immunoglobulin A (IgA) nephropathy and healthy individuals.
AB  - Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis
      worldwide and is histologically characterized by the deposition of IgA1 and
      consequent inflammation in the glomerular mesangium. Prior studies suggested that
      serum IgA1 from IgAN patients contains aberrant, undergalactosylated O-glycans,
      for example, Tn antigen and its sialylated version, SialylTn (STn), but the
      mechanisms underlying aberrant O-glycosylation are not well understood. Here we
      have used serial lectin separation technologies, Western blot, enzymatic
      modifications, and mass spectrometry to explore whether there are different
      glycoforms of IgA1 in plasma from patients with IgAN and healthy individuals.
      Although total plasma IgA in IgAN patients was elevated ~ 1.6-fold compared with
      that in healthy donors, IgA1 in all samples was unexpectedly separable into two
      distinct glycoforms: one with core 1 based O-glycans, and the other exclusively
      containing Tn/STn structures. Importantly, Tn antigen present on IgA1 from IgAN
      patients and controls was convertible into the core 1 structure in vitro by
      recombinant T-synthase. Our results demonstrate that undergalactosylation of O
      glycans in IgA1 is not restricted to IgAN and suggest that in vivo inefficiency
      of T-synthase toward IgA1 in a subpopulation of B or plasma cells, as well as
      overall elevation of IgA, may contribute to IgAN pathogenesis.

PMID- 25071159
TI  - Macrophages derived from infiltrating monocytes mediate autoimmune myelin
      destruction.

PMID- 25071160
TI  - Critical role for CX3CR1+ mononuclear phagocytes in intestinal homeostasis.

PMID- 25071161
TI  - The in-betweeners: MAIT cells join the innate-like lymphocytes gang.

PMID- 25071163
TI  - Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune
      response in vivo.
AB  - Eosinophils natively inhabit the small intestine, but a functional role for them
      there has remained elusive. Here, we show that eosinophil-deficient mice were
      protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and
      Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils.
      Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from
      the intestine to draining lymph nodes, events necessary for Th2 priming.
      Eosinophil activation in vitro and in vivo led to degranulation of eosinophil
      peroxidase, a granule protein whose enzymatic activity promoted DC activation in
      mice and humans in vitro, and intestinal and extraintestinal mouse DC activation
      and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced
      responses to ovalbumin seen after immunization. Thus, eosinophils can be critical
      contributors to the intestinal immune system, and granule-mediated shaping of DC
      responses can promote both intestinal and extraintestinal adaptive immunity. 

PMID- 25071164
TI  - Calorie restriction does not elicit a robust extension of replicative lifespan in
      Saccharomyces cerevisiae.
AB  - Calorie restriction (CR) is often described as the most robust manner to extend
      lifespan in a large variety of organisms. Hence, considerable research effort is
      directed toward understanding the mechanisms underlying CR, especially in the
      yeast Saccharomyces cerevisiae. However, the effect of CR on lifespan has never
      been systematically reviewed in this organism. Here, we performed a meta-analysis
      of replicative lifespan (RLS) data published in more than 40 different papers.
      Our analysis revealed that there is significant variation in the reported RLS
      data, which appears to be mainly due to the low number of cells analyzed per
      experiment. Furthermore, we found that the RLS measured at 2% (wt/vol) glucose in
      CR experiments is partly biased toward shorter lifespans compared with identical
      lifespan measurements from other studies. Excluding the 2% (wt/vol) glucose
      experiments from CR experiments, we determined that the average RLS of the yeast
      strains BY4741 and BY4742 is 25.9 buds at 2% (wt/vol) glucose and 30.2 buds under
      CR conditions. RLS measurements with a microfluidic dissection platform produced
      identical RLS data at 2% (wt/vol) glucose. However, CR conditions did not induce
      lifespan extension. As we excluded obvious methodological differences, such as
      temperature and medium, as causes, we conclude that subtle method-specific
      factors are crucial to induce lifespan extension under CR conditions in S.
      cerevisiae. 

PMID- 25071162
TI  - Fibroblast heterogeneity in the cancer wound.
AB  - Fibroblasts regulate the structure and function of healthy tissues, participate
      transiently in tissue repair after acute inflammation, and assume an aberrant
      stimulatory role during chronic inflammatory states including cancer. Such cancer
      associated fibroblasts (CAFs) modulate the tumor microenvironment and influence
      the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting
      manner. These pleiotropic functions highlight the inherent plasticity of
      fibroblasts and may provide new avenues to understand and therapeutically
      intervene in malignancies. We discuss the emerging themes of CAF biology in the
      context of tumorigenesis and therapy. 

PMID- 25071165
TI  - Development of an antibody-based, modular biosensor for 129Xe NMR molecular
      imaging of cells at nanomolar concentrations.
AB  - Magnetic resonance imaging (MRI) is seriously limited when aiming for
      visualization of targeted contrast agents. Images are reconstructed from the weak
      diamagnetic properties of the sample and require an abundant molecule like water
      as the reporter. Micromolar to millimolar concentrations of conventional contrast
      agents are needed to generate image contrast, thus excluding many molecular
      markers as potential targets. To address this limitation, we developed and
      characterized a functional xenon NMR biosensor that can identify a specific cell
      surface marker by targeted (129)Xe MRI. Cells expressing the cell surface protein
      CD14 can be spatially distinguished from control cells with incorporation of as
      little as 20 nM of the xenon MRI readout unit, cryptophane-A. Cryptophane-A
      serves as a chemical host for hyperpolarized nuclei and facilitates the
      sensitivity enhancement achieved by xenon MRI. Although this paper describes the
      application of a CD14-specific biosensor, the construct has been designed in a
      versatile, modular fashion. This allows for quick and easy adaptation of the
      biosensor to any cell surface target for which there is a specific antibody. In
      addition, the modular design facilitates the creation of a multifunctional probe
      that incorporates readout modules for different detection methods, such as
      fluorescence, to complement the primary MRI readout. This modular antibody-based
      approach not only offers a practical technique with which to screen targets, but
      one which can be readily applied as the xenon MRI field moves closer to molecular
      imaging applications in vivo. 

PMID- 25071167
TI  - Experimental evolution of prepared learning.
AB  - Animals learn some things more easily than others. To explain this so-called
      prepared learning, investigators commonly appeal to the evolutionary history of
      stimulus-consequence relationships experienced by a population or species. We
      offer a simple model that formalizes this long-standing hypothesis. The key
      variable in our model is the statistical reliability of the association between
      stimulus, action, and consequence. We use experimental evolution to test this
      hypothesis in populations of Drosophila. We systematically manipulated the
      reliability of two types of experience (the pairing of the aversive chemical
      quinine with color or with odor). Following 40 generations of evolution, data
      from learning assays support our basic prediction: Changes in learning abilities
      track the reliability of associations during a population's selective history. In
      populations where, for example, quinine-color pairings were unreliable but
      quinine-odor pairings were reliable, we find increased sensitivity to learning
      the quinine-odor experience and reduced sensitivity to learning quinine-color. To
      the best of our knowledge this is the first experimental demonstration of the
      evolution of prepared learning. 

PMID- 25071166
TI  - CRTC1/MAML2 gain-of-function interactions with MYC create a gene signature
      predictive of cancers with CREB-MYC involvement.
AB  - Chimeric oncoproteins created by chromosomal translocations are among the most
      common genetic mutations associated with tumorigenesis. Malignant mucoepidermoid
      salivary gland tumors, as well as a growing number of solid epithelial-derived
      tumors, can arise from a recurrent t (11, 19)(q21;p13.1) translocation that
      generates an unusual chimeric cAMP response element binding protein (CREB)
      regulated transcriptional coactivator 1 (CRTC1)/mastermind-like 2 (MAML2) (C1/M2)
      oncoprotein comprised of two transcriptional coactivators, the CRTC1 and the
      NOTCH/RBPJ coactivator MAML2. Accordingly, the C1/M2 oncoprotein induces aberrant
      expression of CREB and NOTCH target genes. Surprisingly, here we report a gain-of
      function activity of the C1/M2 oncoprotein that directs its interactions with
      myelocytomatosis oncogene (MYC) proteins and the activation of MYC transcription
      targets, including those involved in cell growth and metabolism, survival, and
      tumorigenesis. These results were validated in human mucoepidermoid tumor cells
      that harbor the t (11, 19)(q21;p13.1) translocation and express the C1/M2
      oncoprotein. Notably, the C1/M2-MYC interaction is necessary for C1/M2-driven
      cell transformation, and the C1/M2 transcriptional signature predicts other human
      malignancies having combined involvement of MYC and CREB. These findings suggest
      that such gain-of-function properties may also be manifest in other oncoprotein
      fusions found in human cancer and that agents targeting the C1/M2-MYC interface
      represent an attractive strategy for the development of effective and safe
      anticancer therapeutics in tumors harboring the t (11, 19) translocation. 

PMID- 25071168
TI  - Intergenerational transmission of emotional trauma through amygdala-dependent
      mother-to-infant transfer of specific fear.
AB  - Emotional trauma is transmitted across generations. For example, children
      witnessing their parent expressing fear to specific sounds or images begin to
      express fear to those cues. Within normal range, this is adaptive, although
      pathological fear, such as occurs in posttraumatic stress disorder or specific
      phobias, is also socially transmitted to children and is thus of clinical
      concern. Here, using a rodent model, we report a mother-to-infant transfer of
      fear to a novel peppermint odor, which is dependent on the mother expressing fear
      to that smell in pups' presence. Examination of pups' neural activity using c-Fos
      early gene expression and (14)C 2-deoxyglucose autoradiography during mother-to
      infant fear transmission revealed lateral and basal amygdala nuclei activity,
      with a causal role highlighted by pharmacological inactivation of pups' amygdala
      preventing the fear transmission. Maternal presence was not needed for fear
      transmission, because an elevation of pups' corticosterone induced by the odor of
      the frightened mother along with a novel peppermint odor was sufficient to
      produce pups' subsequent aversion to that odor. Disruption of axonal tracts from
      the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or
      blockade of pups' alarm odor-induced corticosterone increase prevented transfer
      of fear. These memories are acquired at younger ages compared with amygdala
      dependent odor-shock conditioning and are more enduring following minimal
      conditioning. Our results provide clues to understanding transmission of specific
      fears across generations and its dependence upon maternal induction of pups'
      stress response paired with the cue to induce amygdala-dependent learning
      plasticity. Results are discussed within the context of caregiver emotional
      responses and adaptive vs. pathological fears social transmission. 

PMID- 25071170
TI  - Global view of the protein universe.
AB  - To explore protein space from a global perspective, we consider 9,710 SCOP
      (Structural Classification of Proteins) domains with up to 70% sequence identity
      and present all similarities among them as networks: In the "domain network,"
      nodes represent domains, and edges connect domains that share "motifs," i.e.,
      significantly sized segments of similar sequence and structure. We explore the
      dependence of the network on the thresholds that define the evolutionary
      relatedness of the domains. At excessively strict thresholds the network falls
      apart completely; for very lax thresholds, there are network paths between
      virtually all domains. Interestingly, at intermediate thresholds the network
      constitutes two regions that can be described as "continuous" versus "discrete."
      The continuous region comprises a large connected component, dominated by domains
      with alternating alpha and beta elements, and the discrete region includes the
      rest of the domains in isolated islands, each generally corresponding to a fold.
      We also construct the "motif network," in which nodes represent recurring motifs,
      and edges connect motifs that appear in the same domain. This network also
      features a large and highly connected component of motifs that originate from
      domains with alternating alpha/beta elements (and some all-alpha domains), and
      smaller isolated islands. Indeed, the motif network suggests that nature reuses
      such motifs extensively. The networks suggest evolutionary paths between domains
      and give hints about protein evolution and the underlying biophysics. They
      provide natural means of organizing protein space, and could be useful for the
      development of strategies for protein search and design. 

PMID- 25071171
TI  - The early rise and late demise of New Zealand's last glacial maximum.
AB  - Recent debate on records of southern midlatitude glaciation has focused on
      reconstructing glacier dynamics during the last glacial termination, with
      different results supporting both in-phase and out-of-phase correlations with
      Northern Hemisphere glacial signals. A continuing major weakness in this debate
      is the lack of robust data, particularly from the early and maximum phase of
      southern midlatitude glaciation (~30-20 ka), to verify the competing models. Here
      we present a suite of 58 cosmogenic exposure ages from 17 last-glacial ice limits
      in the Rangitata Valley of New Zealand, capturing an extensive record of glacial
      oscillations between 28-16 ka. The sequence shows that the local last glacial
      maximum in this region occurred shortly before 28 ka, followed by several
      successively less extensive ice readvances between 26-19 ka. The onset of
      Termination 1 and the ensuing glacial retreat is preserved in exceptional detail
      through numerous recessional moraines, indicating that ice retreat between 19-16
      ka was very gradual. Extensive valley glaciers survived in the Rangitata
      catchment until at least 15.8 ka. These findings preclude the previously inferred
      rapid climate-driven ice retreat in the Southern Alps after the onset of
      Termination 1. Our record documents an early last glacial maximum, an overall
      trend of diminishing ice volume in New Zealand between 28-20 ka, and gradual
      deglaciation until at least 15 ka. 

PMID- 25071169
TI  - Eradication of metastatic mouse cancers resistant to immune checkpoint blockade
      by suppression of myeloid-derived cells.
AB  - Impressive responses have been observed in patients treated with checkpoint
      inhibitory anti-programmed cell death-1 (PD-1) or anti-cytotoxic T-lymphocyte
      associated antigen-4 (CTLA-4) antibodies. However, immunotherapy against poorly
      immunogenic cancers remains a challenge. Here we report that treatment with both
      anti-PD-1 and anti-CTLA-4 antibodies was unable to eradicate large, modestly
      immunogenic CT26 tumors or metastatic 4T1 tumors. Cotreatment with epigenetic
      modulating drugs and checkpoint inhibitors markedly improved treatment outcomes,
      curing more than 80% of the tumor-bearing mice. Functional studies revealed that
      the primary targets of the epigenetic modulators were myeloid-derived suppressor
      cells (MDSCs). A PI3K inhibitor that reduced circulating MDSCs also eradicated
      4T1 tumors in 80% of the mice when combined with immune checkpoint inhibitors.
      Thus, cancers resistant to immune checkpoint blockade can be cured by eliminating
      MDSCs. 

PMID- 25071173
TI  - Bacillus subtilis chromosome organization oscillates between two distinct
      patterns.
AB  - Bacterial chromosomes have been found to possess one of two distinct patterns of
      spatial organization. In the first, called "ori-ter" and exemplified by
      Caulobacter crescentus, the chromosome arms lie side-by-side, with the
      replication origin and terminus at opposite cell poles. In the second, observed
      in slow-growing Escherichia coli ("left-ori-right"), the two chromosome arms
      reside in separate cell halves, on either side of a centrally located origin.
      These two patterns, rotated 90 degrees  relative to each other, appear to result
      from different segregation mechanisms. Here, we show that the Bacillus subtilis
      chromosome alternates between them. For most of the cell cycle, newly replicated
      origins are maintained at opposite poles with chromosome arms adjacent to each
      other, in an ori-ter configuration. Shortly after replication initiation, the
      duplicated origins move as a unit to midcell and the two unreplicated arms
      resolve into opposite cell halves, generating a left-ori-right pattern. The
      origins are then actively segregated toward opposite poles, resetting the cycle.
      Our data suggest that the condensin complex and the parABS partitioning system
      are the principal driving forces underlying this oscillatory cycle. We propose
      that the distinct organization patterns observed for bacterial chromosomes
      reflect a common organization-segregation mechanism, and that simple
      modifications to it underlie the unique patterns observed in different species. 

PMID- 25071172
TI  - Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and
      glucagon secretion in mice.
AB  - Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we
      report that hypothalamic PREP is predominantly expressed in the ventromedial
      nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP
      knockdown mice (Prep(gt/gt)) exhibited glucose intolerance, decreased fasting
      insulin, increased fasting glucagon levels, and reduced glucose-induced insulin
      secretion compared with wild-type controls. Consistent with this, central
      infusion of a specific PREP inhibitor, S17092, impaired glucose tolerance and
      decreased insulin levels in wild-type mice. Arguing further for a central mode of
      action of PREP, isolated pancreatic islets showed no difference in glucose
      induced insulin release between Prep(gt/gt) and wild-type mice. Furthermore,
      hyperinsulinemic euglycemic clamp studies showed no difference between
      Prep(gt/gt) and wild-type control mice. Central PREP regulation of insulin and
      glucagon secretion appears to be mediated by the autonomic nervous system because
      Prep(gt/gt) mice have elevated sympathetic outflow and norepinephrine levels in
      the pancreas, and propranolol treatment reversed glucose intolerance in these
      mice. Finally, re-expression of PREP by bilateral VMH injection of adeno
      associated virus-PREP reversed the glucose-intolerant phenotype of the
      Prep(gt/gt) mice. Taken together, our results unmask a previously unknown player
      in central regulation of glucose metabolism and pancreatic function. 

PMID- 25071174
TI  - Multiyear predictability of tropical marine productivity.
AB  - With the emergence of decadal predictability simulations, research toward
      forecasting variations of the climate system now covers a large range of
      timescales. However, assessment of the capacity to predict natural variations of
      relevant biogeochemical variables like carbon fluxes, pH, or marine primary
      productivity remains unexplored. Among these, the net primary productivity (NPP)
      is of particular relevance in a forecasting perspective. Indeed, in regions like
      the tropical Pacific (30 degrees N-30 degrees S), NPP exhibits natural
      fluctuations at interannual to decadal timescales that have large impacts on
      marine ecosystems and fisheries. Here, we investigate predictions of NPP
      variations over the last decades (i.e., from 1997 to 2011) with an Earth system
      model within the tropical Pacific. Results suggest a predictive skill for NPP of
      3 y, which is higher than that of sea surface temperature (1 y). We attribute the
      higher predictability of NPP to the poleward advection of nutrient anomalies
      (nitrate and iron), which sustain fluctuations in phytoplankton productivity over
      several years. These results open previously unidentified perspectives to the
      development of science-based management approaches to marine resources relying on
      integrated physical-biogeochemical forecasting systems. 

PMID- 25071175
TI  - Addiction to multiple oncogenes can be exploited to prevent the emergence of
      therapeutic resistance.
AB  - Many cancers exhibit sensitivity to the inhibition of a single genetic lesion, a
      property that has been successfully exploited with oncogene-targeted
      therapeutics. However, inhibition of single oncogenes often fails to result in
      sustained tumor regression due to the emergence of therapy-resistant cells. Here,
      we report that MYC-driven lymphomas frequently acquire activating mutations in
      beta-catenin, including a previously unreported mutation in a splice acceptor
      site. Tumors with these genetic lesions are highly dependent on beta-catenin for
      their survival and the suppression of beta-catenin resulted in marked apoptosis
      causally related to a decrease in Bcl-xL expression. Using a novel inducible
      inhibitor of beta-catenin, we illustrate that, although MYC withdrawal or beta
      catenin inhibition alone results in initial tumor regression, most tumors
      ultimately recurred, mimicking the clinical response to single-agent targeted
      therapy. Importantly, the simultaneous combined inhibition of both MYC and beta
      catenin promoted more rapid tumor regression and successfully prevented tumor
      recurrence. Hence, we demonstrated that MYC-induced tumors are addicted to mutant
      beta-catenin, and the combined inactivation of MYC and beta-catenin induces
      sustained tumor regression. Our results provide a proof of principle that
      targeting multiple oncogene addicted pathways can prevent therapeutic resistance.

PMID- 25071176
TI  - Economic demand predicts addiction-like behavior and therapeutic efficacy of
      oxytocin in the rat.
AB  - Development of new treatments for drug addiction will depend on high-throughput
      screening in animal models. However, an addiction biomarker fit for rapid
      testing, and useful in both humans and animals, is not currently available.
      Economic models are promising candidates. They offer a structured quantitative
      approach to modeling behavior that is mathematically identical across species,
      and accruing evidence indicates economic-based descriptors of human behavior may
      be particularly useful biomarkers of addiction severity. However, economic demand
      has not yet been established as a biomarker of addiction-like behavior in
      animals, an essential final step in linking animal and human studies of addiction
      through economic models. We recently developed a mathematical approach for
      rapidly modeling economic demand in rats trained to self-administer cocaine. We
      show here that economic demand, as both a spontaneous trait and induced state,
      predicts addiction-like behavior, including relapse propensity, drug seeking in
      abstinence, and compulsive (punished) drug taking. These findings confirm
      economic demand as a biomarker of addiction-like behavior in rats. They also
      support the view that excessive motivation plays an important role in addiction
      while extending the idea that drug dependence represents a shift from initially
      recreational to compulsive drug use. Finally, we found that economic demand for
      cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in
      attenuating cocaine-seeking behaviors across individuals, demonstrating that
      economic measures may be used to rapidly identify the clinical utility of
      prospective addiction treatments. 

PMID- 25071177
TI  - FGF2 is a target and a trigger of epigenetic mechanisms associated with
      differences in emotionality: partnership with H3K9me3.
AB  - Posttranslational modifications of histone tails in chromatin template can result
      from environmental experiences such as stress and substance abuse. However, the
      role of epigenetic modifications as potential predisposing factors in affective
      behavior is less well established. To address this question, we used our
      selectively bred lines of high responder (bHR) and low responder (bLR) rats that
      show profound and stable differences in affective responses, with bLRs being
      prone to anxiety- and depression-like behavior and bHRs prone to addictive
      behavior. We first asked whether these phenotypes are associated with basal
      differences in epigenetic profiles. Our results reveal broad between-group
      differences in basal levels of trimethylated histone protein H3 at lysine 9
      (H3K9me3) in hippocampus (HC), amygdala, and nucleus accumbens. Moreover, levels
      of association of H3K9me3 at Glucocorticoid Receptor (GR) and Fibroblast growth
      Factor 2 (FGF2) promoters differ reciprocally between bHRs and bLRs in these
      regions, consistent with these genes' opposing levels of expression and roles in
      modulating anxiety behavior. Importantly, this basal epigenetic pattern is
      modifiable by FGF2, a factor that modulates anxiety behavior. Thus, early-life
      FGF2, which decreases anxiety, altered the levels of H3K9me3 and its binding at
      FGF2 and GR promoters of bLRs rendering them more similar to bHRs. Conversely,
      knockdown of HC FGF2 altered both anxiety behavior and levels of H3K9me3 in bHRs,
      rendering them more bLR-like. These findings implicate FGF2 as a modifier of
      epigenetic mechanisms associated with emotional responsiveness, and point to
      H3K9me3 as a key player in the regulation of affective vulnerability. 

PMID- 25071178
TI  - Anomalously robust valley polarization and valley coherence in bilayer WS2.
AB  - We report the observation of anomalously robust valley polarization and valley
      coherence in bilayer WS2. The polarization of the photoluminescence from bilayer
      WS2 follows that of the excitation source with both circular and linear
      polarization, and remains even at room temperature. The near-unity circular
      polarization of the luminescence reveals the coupling of spin, layer, and valley
      degree of freedom in bilayer system, and the linearly polarized photoluminescence
      manifests quantum coherence between the two inequivalent band extrema in momentum
      space, namely, the valley quantum coherence in atomically thin bilayer WS2. This
      observation provides insight into quantum manipulation in atomically thin
      semiconductors. 

PMID- 25071179
TI  - Astrocytes contribute to gamma oscillations and recognition memory.
AB  - Glial cells are an integral part of functional communication in the brain. Here
      we show that astrocytes contribute to the fast dynamics of neural circuits that
      underlie normal cognitive behaviors. In particular, we found that the selective
      expression of tetanus neurotoxin (TeNT) in astrocytes significantly reduced the
      duration of carbachol-induced gamma oscillations in hippocampal slices. These
      data prompted us to develop a novel transgenic mouse model, specifically with
      inducible tetanus toxin expression in astrocytes. In this in vivo model, we found
      evidence of a marked decrease in electroencephalographic (EEG) power in the gamma
      frequency range in awake-behaving mice, whereas neuronal synaptic activity
      remained intact. The reduction in cortical gamma oscillations was accompanied by
      impaired behavioral performance in the novel object recognition test, whereas
      other forms of memory, including working memory and fear conditioning, remained
      unchanged. These results support a key role for gamma oscillations in recognition
      memory. Both EEG alterations and behavioral deficits in novel object recognition
      were reversed by suppression of tetanus toxin expression. These data reveal an
      unexpected role for astrocytes as essential contributors to information
      processing and cognitive behavior. 

PMID- 25071180
TI  - Efficient UV-induced charge separation and recombination in an 8-oxoguanine
      containing dinucleotide.
AB  - During the early evolution of life, 8-oxo-7,8-dihydro-2'-deoxyguanosine (O) may
      have functioned as a proto-flavin capable of repairing cyclobutane pyrimidine
      dimers in DNA or RNA by photoinduced electron transfer using longer wavelength
      UVB radiation. To investigate the ability of O to act as an excited-state
      electron donor, a dinucleotide mimic of the FADH2 cofactor containing O at the 5'
      end and 2'-deoxyadenosine at the 3'-end was studied by femtosecond transient
      absorption spectroscopy in aqueous solution. Following excitation with a UV
      pulse, a broadband mid-IR pulse probed vibrational modes of ground-state and
      electronically excited molecules in the double-bond stretching region. Global
      analysis of time- and frequency-resolved transient absorption data coupled with
      ab initio quantum mechanical calculations reveal vibrational marker bands of
      nucleobase radical ions formed by electron transfer from O to 2'-deoxyadenosine.
      The quantum yield of charge separation is 0.4 at 265 nm, but decreases to 0.1 at
      295 nm. Charge recombination occurs in 60 ps before the O radical cation can lose
      a deuteron to water. Kinetic and thermodynamic considerations strongly suggest
      that all nucleobases can undergo ultrafast charge separation when pi-stacked in
      DNA or RNA. Interbase charge transfer is proposed to be a major decay pathway for
      UV excited states of nucleic acids of great importance for photostability as well
      as photoredox activity. 

PMID- 25071181
TI  - EGF receptor uses SOS1 to drive constitutive activation of NFkappaB in cancer
      cells.
AB  - Activation of nuclear factor kappaB (NFkappaB) is a central event in the
      responses of normal cells to inflammatory signals, and the abnormal constitutive
      activation of NFkappaB is important for the survival of most cancer cells. In
      nonmalignant human cells, EGF stimulates robust activation of NFkappaB. The
      kinase activity of the EGF receptor (EGFR) is required, because the potent and
      specific inhibitor erlotinib blocks the response. Down-regulating EGFR expression
      or inhibiting EGFR with erlotinib impairs constitutive NFkappaB activation in
      several different types of cancer cells and, conversely, increased activation of
      NFkappaB leads to erlotinib resistance in these cells. We conclude that EGF is an
      important mediator of NFkappaB activation in cancer cells. To explore the
      mechanism, we selected an erlotinib-resistant cell line in which the guanine
      nucleotide exchange factor Son of Sevenless 1 (SOS1), well known to be important
      for EGF-dependent signaling to MAP kinases, is overexpressed. Increased
      expression of SOS1 increases NFkappaB activation in several different types of
      cancer cells, and ablation of SOS1 inhibits EGF-induced NFkappaB activation in
      these cells, indicating that SOS1 is a functional component of the pathway
      connecting EGFR to NFkappaB activation. Importantly, the guanine nucleotide
      exchange activity of SOS1 is not required for NFkappaB activation. 

PMID- 25071182
TI  - The habenula encodes negative motivational value associated with primary
      punishment in humans.
AB  - Learning what to approach, and what to avoid, involves assigning value to
      environmental cues that predict positive and negative events. Studies in animals
      indicate that the lateral habenula encodes the previously learned negative
      motivational value of stimuli. However, involvement of the habenula in dynamic
      trial-by-trial aversive learning has not been assessed, and the functional role
      of this structure in humans remains poorly characterized, in part, due to its
      small size. Using high-resolution functional neuroimaging and computational
      modeling of reinforcement learning, we demonstrate positive habenula responses to
      the dynamically changing values of cues signaling painful electric shocks, which
      predict behavioral suppression of responses to those cues across individuals. By
      contrast, negative habenula responses to monetary reward cue values predict
      behavioral invigoration. Our findings show that the habenula plays a key role in
      an online aversive learning system and in generating associated motivated
      behavior in humans. 

PMID- 25071183
TI  - Upper-tropospheric moistening in response to anthropogenic warming.
AB  - Water vapor in the upper troposphere strongly regulates the strength of water
      vapor feedback, which is the primary process for amplifying the response of the
      climate system to external radiative forcings. Monitoring changes in upper
      tropospheric water vapor and scrutinizing the causes of such changes are
      therefore of great importance for establishing the credibility of model
      projections of past and future climates. Here, we use coupled ocean-atmosphere
      model simulations under different climate-forcing scenarios to investigate
      satellite-observed changes in global-mean upper-tropospheric water vapor. Our
      analysis demonstrates that the upper-tropospheric moistening observed over the
      period 1979-2005 cannot be explained by natural causes and results principally
      from an anthropogenic warming of the climate. By attributing the observed
      increase directly to human activities, this study verifies the presence of the
      largest known feedback mechanism for amplifying anthropogenic climate change. 

PMID- 25071184
TI  - GADD45gamma regulates the thermogenic capacity of brown adipose tissue.
AB  - The coactivator peroxisome proliferator-activated receptor-gamma coactivator 1
      alpha (PGC-1alpha) is widely considered a central transcriptional regulator of
      adaptive thermogenesis in brown adipose tissue (BAT). However, mice lacking PGC
      1alpha specifically in adipose tissue have only mild thermogenic defects,
      suggesting the presence of additional regulators. Using the activity of estrogen
      related receptors (ERRs), downstream effectors of PGC-1alpha, as read-out in a
      high-throughput genome-wide cDNA screen, we identify here growth arrest and DNA
      damage-inducible protein 45 gamma (GADD45gamma) as a cold-induced activator of
      uncoupling protein 1 (UCP1) and oxidative capacity in BAT. Mice lacking
      Gadd45gamma have defects in Ucp1 induction and the thermogenic response to cold.
      GADD45gamma works by activating MAPK p38, which is a potent activator of ERRbeta
      and ERRgamma transcriptional function. GADD45gamma activates ERRgamma
      independently of PGC-1 coactivators, yet synergizes with PGC-1alpha to induce the
      thermogenic program. Our findings elucidate a previously unidentified
      GADD45gamma/p38/ERRgamma pathway that regulates BAT thermogenesis and may enable
      new approaches for the stimulation of energy expenditure. Our study also
      implicates GADD45 proteins as general metabolic regulators. 

PMID- 25071185
TI  - Cyclin-dependent kinases regulate lysosomal degradation of hypoxia-inducible
      factor 1alpha to promote cell-cycle progression.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates
      adaptive responses to oxygen deprivation. In addition, the HIF-1alpha subunit has
      a nontranscriptional role as a negative regulator of DNA replication through
      effects on minichromosome maintenance helicase loading and activation. However,
      some cell types continue to replicate under hypoxic conditions. The mechanism by
      which these cells maintain proliferation in the presence of elevated HIF-1alpha
      levels is unclear. Here we report that HIF-1alpha physically and functionally
      interacts with cyclin-dependent kinase 1 (Cdk1) and Cdk2. Cdk1 activity blocks
      lysosomal degradation of HIF-1alpha and increases HIF-1alpha protein stability
      and transcriptional activity. By contrast, Cdk2 activity promotes lysosomal
      degradation of HIF-1alpha at the G1/S phase transition. Blocking lysosomal
      degradation by genetic or pharmacological means leads to HIF-1alpha-dependent
      cell-cycle arrest, demonstrating that lysosomal degradation of HIF-1alpha is an
      essential step for the maintenance of cell-cycle progression under hypoxic
      conditions. 

PMID- 25071186
TI  - Sphalerite is a geochemical catalyst for carbon-hydrogen bond activation.
AB  - Reactions among minerals and organic compounds in hydrothermal systems are
      critical components of the Earth's deep carbon cycle, provide energy for the deep
      biosphere, and may have implications for the origins of life. However, there is
      limited information as to how specific minerals influence the reactivity of
      organic compounds. Here we demonstrate mineral catalysis of the most fundamental
      component of an organic reaction: the breaking and making of a covalent bond. In
      the absence of mineral, hydrothermal reaction of cis- and trans-1,2
      dimethylcyclohexane is extremely slow and generates many products. In the
      presence of sphalerite (ZnS), however, the reaction rate increases dramatically
      and one major product is formed: the corresponding stereoisomer. Isotope studies
      show that the sphalerite acts as a highly specific heterogeneous catalyst for
      activation of a single carbon-hydrogen bond in the dimethylcyclohexanes. 

PMID- 25071188
TI  - Novel approach to numerical measurements of the configurational entropy in
      supercooled liquids.
AB  - The configurational entropy is among the key observables to characterize
      experimentally the formation of a glass. Physically, it quantifies the
      multiplicity of metastable states in which an amorphous material can be found at
      a given temperature, and its temperature dependence provides a major
      thermodynamic signature of the glass transition, which is experimentally
      accessible. Measurements of the configurational entropy require, however, some
      approximations that have often led to ambiguities and contradictory results. Here
      we implement a novel numerical scheme to measure the configurational entropy
      Sigma(T) in supercooled liquids, using a direct determination of the free-energy
      cost to localize the system within a single metastable state at temperature T.
      For two prototypical glass-forming liquids, we find that Sigma(T) disappears
      discontinuously above a temperature Tc, which is slightly lower than the usual
      estimate of the onset temperature for glassy dynamics. This observation is in
      good agreement with theoretical expectations but contrasts sharply with
      alternative numerical methods. While the temperature dependence of Sigma(T)
      correlates with the glass fragility, we show that the validity of the Adam-Gibbs
      relation (relating configurational entropy to structural relaxation time)
      established in earlier numerical studies is smaller than previously thought,
      potentially resolving an important conflict between experiments and simulations. 

PMID- 25071187
TI  - Early remodeling of the neocortex upon episodic memory encoding.
AB  - Understanding the mechanisms by which long-term memories are formed and stored in
      the brain represents a central aim of neuroscience. Prevailing theory suggests
      that long-term memory encoding involves early plasticity within hippocampal
      circuits, whereas reorganization of the neocortex is thought to occur weeks to
      months later to subserve remote memory storage. Here we report that long-term
      memory encoding can elicit early transcriptional, structural, and functional
      remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing,
      ultrastructural imaging, and whole-cell recording in wild-type mice suggest that
      contextual fear conditioning initiates a transcriptional program in the medial
      prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic
      active zone and postsynaptic density, enhanced dendritic spine plasticity, and
      increased synaptic efficacy. To address the real-time contribution of the mPFC to
      long-term memory encoding, we performed temporally precise optogenetic inhibition
      of excitatory mPFC neurons during contextual fear conditioning. Using this
      approach, we found that real-time inhibition of the mPFC inhibited activation of
      the entorhinal-hippocampal circuit and impaired the formation of long-term
      associative memory. These findings suggest that encoding of long-term episodic
      memory is associated with early remodeling of neocortical circuits, identify the
      prefrontal cortex as a critical regulator of encoding-induced hippocampal
      activation and long-term memory formation, and have important implications for
      understanding memory processing in healthy and diseased brain states. 

PMID- 25071189
TI  - Shape recognition and classification in electro-sensing.
AB  - This paper aims at advancing the field of electro-sensing. It exhibits physical
      mechanisms underlying shape perception for weakly electric fish. These fish
      orient themselves at night in complete darkness by using their active
      electrolocation system. They generate a stable, relatively high-frequency, weak
      electric field and perceive the transdermal potential modulations caused by a
      nearby target with different electromagnetic properties than the surrounding
      water. The main result of this paper is a scheme that explains how weakly
      electric fish might identify and classify a target, knowing in advance that the
      latter belongs to a certain collection of shapes. The scheme is designed to
      recognize living biological organisms. It exploits the frequency dependence of
      the electromagnetic properties of living organisms, which comes from the
      capacitive effects generated by the cell membrane structure. When measurements
      are taken at multiple frequencies, the fish might use the spectral content of the
      perceived transdermal potential modulations to classify the living target. 

PMID- 25071190
TI  - Network-level architecture and the evolutionary potential of underground
      metabolism.
AB  - A central unresolved issue in evolutionary biology is how metabolic innovations
      emerge. Low-level enzymatic side activities are frequent and can potentially be
      recruited for new biochemical functions. However, the role of such underground
      reactions in adaptation toward novel environments has remained largely unknown
      and out of reach of computational predictions, not least because these issues
      demand analyses at the level of the entire metabolic network. Here, we provide a
      comprehensive computational model of the underground metabolism in Escherichia
      coli. Most underground reactions are not isolated and 45% of them can be fully
      wired into the existing network and form novel pathways that produce key
      precursors for cell growth. This observation allowed us to conduct an integrated
      genome-wide in silico and experimental survey to characterize the evolutionary
      potential of E. coli to adapt to hundreds of nutrient conditions. We revealed
      that underground reactions allow growth in new environments when their activity
      is increased. We estimate that at least ~20% of the underground reactions that
      can be connected to the existing network confer a fitness advantage under
      specific environments. Moreover, our results demonstrate that the genetic basis
      of evolutionary adaptations via underground metabolism is computationally
      predictable. The approach used here has potential for various application areas
      from bioengineering to medical genetics. 

PMID- 25071191
TI  - Rebound burst firing in the reticular thalamus is not essential for
      pharmacological absence seizures in mice.
AB  - Intrinsic burst and rhythmic burst discharges (RBDs) are elicited by activation
      of T-type Ca(2+) channels in the thalamic reticular nucleus (TRN). TRN bursts are
      believed to be critical for generation and maintenance of thalamocortical
      oscillations, leading to the spike-and-wave discharges (SWDs), which are the
      hallmarks of absence seizures. We observed that the RBDs were completely
      abolished, whereas tonic firing was significantly increased, in TRN neurons from
      mice in which the gene for the T-type Ca(2+) channel, CaV3.3, was deleted
      (CaV3.3(-/-)). Contrary to expectations, there was an increased susceptibility to
      drug-induced SWDs both in CaV3.3(-/-) mice and in mice in which the CaV3.3 gene
      was silenced predominantly in the TRN. CaV3.3(-/-) mice also showed enhanced
      inhibitory synaptic drive onto TC neurons. Finally, a double knockout of both
      CaV3.3 and CaV3.2, which showed complete elimination of burst firing and RBDs in
      TRN neurons, also displayed enhanced drug-induced SWDs and absence seizures. On
      the other hand, tonic firing in the TRN was increased in these mice, suggesting
      that increased tonic firing in the TRN may be sufficient for drug-induced SWD
      generation in the absence of burst firing. These results call into question the
      role of burst firing in TRN neurons in the genesis of SWDs, calling for a
      rethinking of the mechanism for absence seizure induction. 

PMID- 25071193
TI  - Quantifying the semantics of search behavior before stock market moves.
AB  - Technology is becoming deeply interwoven into the fabric of society. The Internet
      has become a central source of information for many people when making day-to-day
      decisions. Here, we present a method to mine the vast data Internet users create
      when searching for information online, to identify topics of interest before
      stock market moves. In an analysis of historic data from 2004 until 2012, we draw
      on records from the search engine Google and online encyclopedia Wikipedia as
      well as judgments from the service Amazon Mechanical Turk. We find evidence of
      links between Internet searches relating to politics or business and subsequent
      stock market moves. In particular, we find that an increase in search volume for
      these topics tends to precede stock market falls. We suggest that extensions of
      these analyses could offer insight into large-scale information flow before a
      range of real-world events. 

PMID- 25071192
TI  - Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs.
AB  - Activity-dependent changes in synaptic strength have long been postulated as
      cellular correlates of learning and memory. Long-term potentiation (LTP), a well
      characterized form of synaptic plasticity, is often expressed as an increase in
      the number of postsynaptic AMPA-type glutamate receptors (AMPARs). Although the
      precise molecular mechanisms governing LTP remain elusive, this study identifies
      one member of the sorting nexin family, Sorting Nexin 27 (SNX27), as a critical
      component in this process. The ability of sorting nexins to bind specific
      phospholipids as well as their propensity to form protein-protein complexes,
      points to a role for these proteins in membrane trafficking and protein sorting.
      Here, we demonstrate that SNX27 binds to AMPARs, and that this interaction is
      regulated in an activity-dependent manner. Furthermore, we provide evidence that
      SNX27 is synaptically enriched and its level of expression regulates targeting of
      AMPARs to the neuronal surface. Loss of SNX27 abolishes recruitment of surface
      AMPARs during chemical LTP. Collectively, our data suggest a role for SNX27 in
      modulating synaptic plasticity through regulated interaction with AMPARs. 

PMID- 25071194
TI  - Elimination of damaged mitochondria through mitophagy reduces mitochondrial
      oxidative stress and increases tolerance to trichothecenes.
AB  - Trichothecene mycotoxins are natural contaminants of small grain cereals and are
      encountered in the environment, posing a worldwide threat to human and animal
      health. Their mechanism of toxicity is poorly understood, and little is known
      about cellular protection mechanisms against trichothecenes. We previously
      identified inhibition of mitochondrial protein synthesis as a novel mechanism for
      trichothecene-induced cell death. To identify cellular functions involved in
      trichothecene resistance, we screened the Saccharomyces cerevisiae deletion
      library for increased sensitivity to nonlethal concentrations of trichothecin
      (Tcin) and identified 121 strains exhibiting higher sensitivity than the parental
      strain. The largest group of sensitive strains had significantly higher reactive
      oxygen species (ROS) levels relative to the parental strain. A dose-dependent
      increase in ROS levels was observed in the parental strain treated with different
      trichothecenes, but not in a petite version of the parental strain or in the
      presence of a mitochondrial membrane uncoupler, indicating that mitochondria are
      the main site of ROS production due to toxin exposure. Cytotoxicity of
      trichothecenes was alleviated after treatment of the parental strain and highly
      sensitive mutants with antioxidants, suggesting that oxidative stress contributes
      to trichothecene sensitivity. Cotreatment with rapamycin and trichothecenes
      reduced ROS levels and cytotoxicity in the parental strain relative to the
      trichothecene treatment alone, but not in mitophagy deficient mutants, suggesting
      that elimination of trichothecene-damaged mitochondria by mitophagy improves cell
      survival. These results reveal that increased mitophagy is a cellular protection
      mechanism against trichothecene-induced mitochondrial oxidative stress and a
      potential target for trichothecene resistance. 

PMID- 25071195
TI  - Spectroscopic signatures of ozone at the air-water interface and photochemistry
      implications.
AB  - First-principles simulations suggest that additional OH formation in the
      troposphere can result from ozone interactions with the surface of cloud
      droplets. Ozone exhibits an affinity for the air-water interface, which modifies
      its UV and visible light spectroscopic signatures and photolytic rate constant in
      the troposphere. Ozone cross sections on the red side of the Hartley band (290-
      to 350-nm region) and in the Chappuis band (450-700 nm) are increased due to
      electronic ozone-water interactions. This effect, combined with the potential
      contribution of the O3 + hnu -> O((3)P) + O2(X(3)Sigmag(-)) photolytic channel at
      the interface, leads to an enhancement of the OH radical formation rate by four
      orders of magnitude. This finding suggests that clouds can influence the overall
      oxidizing capacity of the troposphere on a global scale by stimulating the
      production of OH radicals through ozone photolysis by UV and visible light at the
      air-water interface.

PMID- 25071196
TI  - Flow disturbances generated by feeding and swimming zooplankton.
AB  - Interactions between planktonic organisms, such as detection of prey, predators,
      and mates, are often mediated by fluid signals. Consequently, many plankton
      predators perceive their prey from the fluid disturbances that it generates when
      it feeds and swims. Zooplankton should therefore seek to minimize the fluid
      disturbance that they produce. By means of particle image velocimetry, we
      describe the fluid disturbances produced by feeding and swimming in zooplankton
      with diverse propulsion mechanisms and ranging from 10-um flagellates to greater
      than millimeter-sized copepods. We show that zooplankton, in which feeding and
      swimming are separate processes, produce flow disturbances during swimming with a
      much faster spatial attenuation (velocity u varies with distance r as u ? r(-3)
      to r(-4)) than that produced by zooplankton for which feeding and propulsion are
      the same process (u ? r(-1) to r(-2)). As a result, the spatial extension of the
      fluid disturbance produced by swimmers is an order of magnitude smaller than that
      produced by feeders at similar Reynolds numbers. The "quiet" propulsion of
      swimmers is achieved either through swimming erratically by short-lasting power
      strokes, generating viscous vortex rings, or by "breast-stroke swimming." Both
      produce rapidly attenuating flows. The more "noisy" swimming of those that are
      constrained by a need to simultaneously feed is due to constantly beating
      flagella or appendages that are positioned either anteriorly or posteriorly on
      the (cell) body. These patterns transcend differences in size and taxonomy and
      have thus evolved multiple times, suggesting a strong selective pressure to
      minimize predation risk. 

PMID- 25071197
TI  - Modeling first impressions from highly variable facial images.
AB  - First impressions of social traits, such as trustworthiness or dominance, are
      reliably perceived in faces, and despite their questionable validity they can
      have considerable real-world consequences. We sought to uncover the information
      driving such judgments, using an attribute-based approach. Attributes (physical
      facial features) were objectively measured from feature positions and colors in a
      database of highly variable "ambient" face photographs, and then used as input
      for a neural network to model factor dimensions (approachability, youthful
      attractiveness, and dominance) thought to underlie social attributions. A linear
      model based on this approach was able to account for 58% of the variance in
      raters' impressions of previously unseen faces, and factor-attribute correlations
      could be used to rank attributes by their importance to each factor. Reversing
      this process, neural networks were then used to predict facial attributes and
      corresponding image properties from specific combinations of factor scores. In
      this way, the factors driving social trait impressions could be visualized as a
      series of computer-generated cartoon face-like images, depicting how attributes
      change along each dimension. This study shows that despite enormous variation in
      ambient images of faces, a substantial proportion of the variance in first
      impressions can be accounted for through linear changes in objectively defined
      features. 

PMID- 25071198
TI  - Spin-dependent electron transport in protein-like single-helical molecules.
AB  - We report on a theoretical study of spin-dependent electron transport through
      single-helical molecules connected by two nonmagnetic electrodes, and explain the
      experiment of significant spin-selective phenomenon observed in alpha-helical
      protein and the contradictory results between the protein and single-stranded
      DNA. Our results reveal that the alpha-helical protein is an efficient spin
      filter and the spin polarization is robust against the disorder. These results
      are in excellent agreement with recent experiments [Mishra D, et al. (2013) Proc
      Natl Acad Sci USA 110(37):14872-14876; Gohler B, et al. (2011) Science
      331(6019):894-897] and may facilitate engineering of chiral-based spintronic
      devices. 

PMID- 25071200
TI  - Footprint of Deepwater Horizon blowout impact to deep-water coral communities.
AB  - On April 20, 2010, the Deepwater Horizon (DWH) blowout occurred, releasing more
      oil than any accidental spill in history. Oil release continued for 87 d and much
      of the oil and gas remained in, or returned to, the deep sea. A coral community
      significantly impacted by the spill was discovered in late 2010 at 1,370 m depth.
      Here we describe the discovery of five previously unknown coral communities near
      the Macondo wellhead and show that at least two additional coral communities were
      impacted by the spill. Although the oil-containing flocullent material that was
      present on corals when the first impacted community was discovered was largely
      gone, a characteristic patchy covering of hydrozoans on dead portions of the
      skeleton allowed recognition of impacted colonies at the more recently discovered
      sites. One of these communities was 6 km south of the Macondo wellhead and over
      90% of the corals present showed the characteristic signs of recent impact. The
      other community, 22 km southeast of the wellhead between 1,850 and 1,950 m depth,
      was more lightly impacted. However, the discovery of this site considerably
      extends the distance from Macondo and depth range of significant impact to
      benthic macrofaunal communities. We also show that most known deep-water coral
      communities in the Gulf of Mexico do not appear to have been acutely impacted by
      the spill, although two of the newly discovered communities near the wellhead
      apparently not impacted by the spill have been impacted by deep-sea fishing
      operations. 

PMID- 25071199
TI  - Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development
      and differentiation.
AB  - The discovery of Ten Eleven Translocation proteins, enzymes that oxidize 5
      methylcytosine (5mC) in DNA, has revealed novel mechanisms for the regulation of
      DNA methylation. We have mapped 5-hydroxymethylcytosine (5hmC) at different
      stages of T-cell development in the thymus and T-cell differentiation in the
      periphery. We show that 5hmC is enriched in the gene body of highly expressed
      genes at all developmental stages and that its presence correlates positively
      with gene expression. Further emphasizing the connection with gene expression, we
      find that 5hmC is enriched in active thymus-specific enhancers and that genes
      encoding key transcriptional regulators display high intragenic 5hmC levels in
      precursor cells at those developmental stages where they exert a positive effect.
      Our data constitute a valuable resource that will facilitate detailed analysis of
      the role of 5hmC in T-cell development and differentiation. 

PMID- 25071201
TI  - The changing face of cognitive gender differences in Europe.
AB  - Cognitive gender differences and the reasons for their origins have fascinated
      researchers for decades. Using nationally representative data to investigate
      gender differences in cognitive performance in middle-aged and older populations
      across Europe, we show that the magnitude of these differences varies
      systematically across cognitive tasks, birth cohorts, and regions, but also that
      the living conditions and educational opportunities individuals are exposed to
      during their formative years are related to their later cognitive performance.
      Specifically, we demonstrate that improved living conditions and less gender
      restricted educational opportunities are associated with increased gender
      differences favoring women in some cognitive functions (i.e., episodic memory)
      and decreases (i.e., numeracy) or elimination of differences in other cognitive
      abilities (i.e., category fluency). Our results suggest that these changes take
      place due to a general increase in women's cognitive performance over time,
      associated with societal improvements in living conditions and educational
      opportunities. 

PMID- 25071202
TI  - Clade extinction appears to balance species diversification in sister lineages of
      Afro-Oriental passerine birds.
AB  - Recent analyses suggest that the number of species in a clade often increases
      rapidly at first, but that diversification subsequently slows, apparently as
      species fill ecological space. Support for diversity dependence comes largely
      from the failure of species richness to increase with clade age in some analyses
      of contemporary diversity. However, clades chosen for analysis generally are
      named taxa and thus are not selected at random. To avoid this potential bias, we
      analyzed the numbers of species and estimated ages of 150 pairs of sister clades
      established by dispersal of ancestral species between the Oriental and African
      biogeographic regions. The observed positive exponential relationship between
      clade size and age suggests that species diversify within clades without apparent
      limit. If this were true, the pattern of accumulation of sister-clade pairs with
      increasing age would be consistent with the random decline and extinction of
      entire clades, maintaining an overall balance in species richness. This "pulse"
      model of diversification is consistent with the fossil record of most groups and
      reconciles conflicting evidence concerning diversity dependence of clade growth. 

PMID- 25071203
TI  - Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T
      cells.
AB  - In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of
      follicular helper T (TFH) cell differentiation; however, its activation
      mechanisms and role in memory responses remain unclear. Here we demonstrate that
      survival of CXCR5(+) TFH memory cells, and thus subsequent recall antibody
      response, require Bcl6 expression. Furthermore, we show that, upon rechallenge
      with soluble antigen Bcl6 in memory TFH cells is rapidly induced in a dendritic
      cell-independent manner and that peptide:class II complexes (pMHC) on cognate
      memory B cells significantly contribute to this induction. Given the previous
      evidence that antigen-specific B cells residing in the follicles acquire antigens
      within minutes of injection, our results suggest that memory B cells present
      antigens to the cognate TFH memory cells, thereby contributing to rapid Bcl6
      reexpression and differentiation of the TFH memory cells during humoral memory
      responses. 

PMID- 25071204
TI  - The role of PI3K/AKT-related PIP5K1alpha and the discovery of its selective
      inhibitor for treatment of advanced prostate cancer.
AB  - Nitrogen-containing heterocyclic compounds are an important class of molecules
      that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol
      4-phosphate 5-kinase-alpha (PIP5Kalpha) is a lipid kinase, similar to PI3K.
      However, the role of PIP5K1alpha in oncogenic processes and the development of
      inhibitors that selectively target PIP5K1alpha have not been reported. In the
      present study we report that overexpression of PIP5K1alpha is associated with
      poor prognosis in prostate cancer and correlates with an elevated level of the
      androgen receptor. Overexpression of PIP5K1alpha in PNT1A nonmalignant cells
      results in an increased AKT activity and an increased survival, as well as
      invasive malignant phenotype, whereas siRNA-mediated knockdown of PIP5K1alpha in
      aggressive PC-3 cells leads to a reduced AKT activity and an inhibition in tumor
      growth in xenograft mice. We further report a previously unidentified role for
      PIP5K1alpha as a druggable target for our newly developed compound ISA-2011B
      using a high-throughput KINOMEscan platform. ISA-2011B was discovered during our
      synthetic studies of C-1 indol-3-yl substituted 1,2,3,4-tetrahydroisoquinolines
      via a Pictet-Spengler approach. ISA-2011B significantly inhibits growth of tumor
      cells in xenograft mice, and we show that this is mediated by targeting
      PIP5K1alpha-associated PI3K/AKT and the downstream survival, proliferation, and
      invasion pathways. Further, siRNA-mediated knockdown of PIP5K1alpha exerts
      similar effects on PC3 cells as ISA-2011B treatment, significantly inhibiting AKT
      activity, increasing apoptosis and reducing invasion. Thus, PIP5K1alpha has high
      potential as a drug target, and compound ISA-2011B is interesting for further
      development of targeted cancer therapy. 

PMID- 25071205
TI  - Structures and organization of adenovirus cement proteins provide insights into
      the role of capsid maturation in virus entry and infection.
AB  - Adenovirus cement proteins play crucial roles in virion assembly, disassembly,
      cell entry, and infection. Based on a refined crystal structure of the adenovirus
      virion at 3.8-A resolution, we have determined the structures of all of the
      cement proteins (IIIa, VI, VIII, and IX) and their organization in two distinct
      layers. We have significantly revised the recent cryoelectron microscopy models
      for proteins IIIa and IX and show that both are located on the capsid exterior.
      Together, the cement proteins exclusively stabilize the hexon shell, thus
      rendering penton vertices the weakest links of the adenovirus capsid. We
      describe, for the first time to our knowledge, the structure of protein VI, a key
      membrane-lytic molecule, and unveil its associations with VIII and core protein
      V, which together glue peripentonal hexons beneath the vertex region and connect
      them to the rest of the capsid on the interior. Following virion maturation, the
      cleaved N-terminal propeptide of VI is observed, reaching deep into the
      peripentonal hexon cavity, detached from the membrane-lytic domain, so that the
      latter can be released. Our results thus provide the molecular basis for the
      requirement of maturation cleavage of protein VI. This process is essential for
      untethering and release of the membrane-lytic region, which is known to mediate
      endosome rupture and delivery of partially disassembled virions into the host
      cell cytoplasm. 

PMID- 25071206
TI  - Structure of beta-galactosidase at 3.2-A resolution obtained by cryo-electron
      microscopy.
AB  - We report the solution structure of Escherichia coli beta-galactosidase (~465
      kDa), solved at ~3.2-A resolution by using single-particle cryo-electron
      microscopy (cryo-EM). Densities for most side chains, including those of residues
      in the active site, and a catalytic Mg(2+) ion can be discerned in the map
      obtained by cryo-EM. The atomic model derived from our cryo-EM analysis closely
      matches the 1.7-A crystal structure with a global rmsd of ~0.66 A. There are
      significant local differences throughout the protein, with clear evidence for
      conformational changes resulting from contact zones in the crystal lattice.
      Inspection of the map reveals that although densities for residues with
      positively charged and neutral side chains are well resolved, systematically
      weaker densities are observed for residues with negatively charged side chains.
      We show that the weaker densities for negatively charged residues arise from
      their greater sensitivity to radiation damage from electron irradiation as
      determined by comparison of density maps obtained by using electron doses ranging
      from 10 to 30 e(-)/A(2). In summary, we establish that it is feasible to use cryo
      EM to determine near-atomic resolution structures of protein complexes (<500 kDa)
      with low symmetry, and that the residue-specific radiation damage that occurs
      with increasing electron dose can be monitored by using dose fractionation tools
      available with direct electron detector technology. 

PMID- 25071207
TI  - Tautomerism provides a molecular explanation for the mutagenic properties of the
      anti-HIV nucleoside 5-aza-5,6-dihydro-2'-deoxycytidine.
AB  - Viral lethal mutagenesis is a strategy whereby the innate immune system or
      mutagenic pool nucleotides increase the error rate of viral replication above the
      error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for
      several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2'
      deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV
      genome, both in tissue culture and in HIV positive patients undergoing KP1212
      monotherapy. This work explored the molecular mechanism(s) underlying the
      mutagenicity of KP1212, and specifically whether tautomerism, a previously
      proposed hypothesis, could explain the biological consequences of this nucleoside
      analog. Establishing tautomerism of nucleic acid bases under physiological
      conditions has been challenging because of the lack of sensitive methods. This
      study investigated tautomerism using an array of spectroscopic, theoretical, and
      chemical biology approaches. Variable temperature NMR and 2D infrared
      spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of
      interconverting tautomers, among which enolic forms dominated. The mutagenic
      properties of KP1212 were determined empirically by in vitro and in vivo
      replication of a single-stranded vector containing a single KP1212. It was found
      that KP1212 paired with both A (10%) and G (90%), which is in accord with
      clinical observations. Moreover, this mutation frequency is sufficient for
      pushing a viral population over its error catastrophe limit, as observed before
      in cell culture studies. Finally, a model is proposed that correlates the
      mutagenicity of KP1212 with its tautomeric distribution in solution. 

PMID- 25071208
TI  - KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the
      early distal convoluted tubule (DCT1).
AB  - The renal phenotype induced by loss-of-function mutations of inwardly rectifying
      potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia,
      metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.4.1
      mutations cause the tubulopathy is not completely understood. Here we demonstrate
      that Kcnj10 is a main contributor to the basolateral K conductance in the early
      distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl
      cotransporter (NCC) in the DCT. Immunostaining demonstrated Kcnj10 and Kcnj16
      were expressed in the basolateral membrane of DCT, and patch-clamp studies
      detected a 40-pS K channel in the basolateral membrane of the DCT1 of p8/p10 wild
      type Kcnj10(+/+) mice (WT). This 40-pS K channel is absent in homozygous Kcnj10(
      /-) (knockout) mice. The disruption of Kcnj10 almost completely eliminated the
      basolateral K conductance and decreased the negativity of the cell membrane
      potential in DCT1. Moreover, the lack of Kcnj10 decreased the basolateral Cl
      conductance, inhibited the expression of Ste20-related proline-alanine-rich
      kinase and diminished the apical NCC expression in DCT. We conclude that Kcnj10
      plays a dominant role in determining the basolateral K conductance and membrane
      potential of DCT1 and that the basolateral K channel activity in the DCT
      determines the apical NCC expression possibly through a Ste20-related proline
      alanine-rich kinase-dependent mechanism. 

PMID- 25071209
TI  - Single-molecule FRET reveals a corkscrew RNA structure for the polymerase-bound
      influenza virus promoter.
AB  - The influenza virus is a major human and animal pathogen responsible for seasonal
      epidemics and occasional pandemics. The genome of the influenza A virus comprises
      eight segments of single-stranded, negative-sense RNA with highly conserved 5'
      and 3' termini. These termini interact to form a double-stranded promoter
      structure that is recognized and bound by the viral RNA-dependent RNA polymerase
      (RNAP); however, no 3D structural information for the influenza polymerase-bound
      promoter exists. Functional studies have led to the proposal of several 2D models
      for the secondary structure of the bound promoter, including a corkscrew model in
      which the 5' and 3' termini form short hairpins. We have taken advantage of an
      insect-cell system to prepare large amounts of active recombinant influenza virus
      RNAP, and used this to develop a highly sensitive single-molecule FRET assay to
      measure distances between fluorescent dyes located on the promoter and map its
      structure both with and without the polymerase bound. These advances enabled the
      direct analysis of the influenza promoter structure in complex with the viral
      RNAP, and provided 3D structural information that is in agreement with the
      corkscrew model for the influenza virus promoter RNA. Our data provide insights
      into the mechanisms of promoter binding by the influenza RNAP and have
      implications for the understanding of the regulatory mechanisms involved in the
      transcription of viral genes and replication of the viral RNA genome. In
      addition, the simplicity of this system should translate readily to the study of
      any virus polymerase-promoter interaction. 

PMID- 25071210
TI  - Quality control of assembly-defective U1 snRNAs by decapping and 5'-to-3'
      exonucleolytic digestion.
AB  - The accurate biogenesis of RNA-protein complexes is a key aspect of eukaryotic
      cells. Defects in Sm protein complex binding to snRNAs are known to reduce levels
      of snRNAs, suggesting an unknown quality control system for small nuclear
      ribonucleoprotein (snRNP) assembly. snRNA quality control may also be relevant in
      spinal muscular atrophy, which is caused by defects in the survival motor neuron
      (SMN)1 gene, an assembly factor for loading the Sm complex on snRNAs and, when
      severely reduced, can lead to reduced levels of snRNAs and splicing defects. To
      determine how assembly-defective snRNAs are degraded, we first demonstrate that
      yeast U1 Sm-mutant snRNAs are degraded either by Rrp6- or by Dcp2-dependent
      decapping/5'-to-3' decay. Knockdown of the decapping enzyme DCP2 in mammalian
      cells also increases the levels of assembly-defective snRNAs and suppresses some
      splicing defects seen in SMN-deficient cells. These results identify a conserved
      mechanism of snRNA quality control, and also suggest a general paradigm wherein
      the phenotype of an "RNP assembly disease" might be suppressed by inhibition of a
      competing RNA quality control mechanism. 

PMID- 25071211
TI  - A critical appraisal of the use of microRNA data in phylogenetics.
AB  - Recent progress in resolving the tree of life continues to expose relationships
      that resist resolution, which drives the search for novel sources of information
      to solve these difficult phylogenetic problems. A recent example, the presence
      and absence of microRNA families, has been vigorously promoted as an ideal source
      of phylogenetic data and has been applied to several perennial phylogenetic
      problems. The utility of such data for phylogenetic inference hinges critically
      both on developing stochastic models that provide a reasonable description of the
      process that give rise to these data, and also on the careful validation of those
      models in real inference scenarios. Remarkably, however, the statistical behavior
      and phylogenetic utility of microRNA data have not yet been rigorously
      characterized. Here we explore the behavior and performance of microRNA
      presence/absence data under a variety of evolutionary models and reexamine
      datasets from several previous studies. We find that highly heterogeneous rates
      of microRNA gain and loss, pervasive secondary loss, and sampling error
      collectively render microRNA-based inference of phylogeny difficult. Moreover,
      our reanalyses fundamentally alter the conclusions for four of the five studies
      that we reexamined. Our results indicate that the capacity of miRNA data to
      resolve the tree of life has been overstated, and we urge caution in their
      application and interpretation. 

PMID- 25071212
TI  - Lactate promotes plasticity gene expression by potentiating NMDA signaling in
      neurons.
AB  - L-lactate is a product of aerobic glycolysis that can be used by neurons as an
      energy substrate. Here we report that in neurons L-lactate stimulates the
      expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268
      through a mechanism involving NMDA receptor activity and its downstream signaling
      cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the
      ensuing increase in intracellular calcium. In parallel to this, L-lactate
      increases intracellular levels of NADH, thereby modulating the redox state of
      neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing
      to NADH increase as a primary mediator of L-lactate effects. The induction of
      plasticity genes is observed both in mouse primary neurons in culture and in vivo
      in the mouse sensory-motor cortex. These results provide insights for the
      understanding of the molecular mechanisms underlying the critical role of
      astrocyte-derived L-lactate in long-term memory and long-term potentiation in
      vivo. This set of data reveals a previously unidentified action of L-lactate as a
      signaling molecule for neuronal plasticity.

PMID- 25071214
TI  - Epigenetic coordination of embryonic heart transcription by dynamically regulated
      long noncoding RNAs.
AB  - The vast majority of mammalian DNA does not encode for proteins but instead is
      transcribed into noncoding (nc)RNAs having diverse regulatory functions. The
      poorly characterized subclass of long ncRNAs (lncRNAs) can epigenetically
      regulate protein-coding genes by interacting locally in cis or distally in trans.
      A few reports have implicated specific lncRNAs in cardiac development or failure,
      but precise details of lncRNAs expressed in hearts and how their expression may
      be altered during embryonic heart development or by adult heart disease is
      unknown. Using comprehensive quantitative RNA sequencing data from mouse hearts,
      livers, and skin cells, we identified 321 lncRNAs present in the heart, 117 of
      which exhibit a cardiac-enriched pattern of expression. By comparing lncRNA
      profiles of normal embryonic (~E14), normal adult, and hypertrophied adult
      hearts, we defined a distinct fetal lncRNA abundance signature that includes 157
      lncRNAs differentially expressed compared with adults (fold-change >= 50%, false
      discovery rate = 0.02) and that was only poorly recapitulated in hypertrophied
      hearts (17 differentially expressed lncRNAs; 13 of these observed in embryonic
      hearts). Analysis of protein-coding mRNAs from the same samples identified 22
      concordantly and 11 reciprocally regulated mRNAs within 10 kb of dynamically
      expressed lncRNAs, and reciprocal relationships of lncRNA and mRNA levels were
      validated for the Mccc1 and Relb genes using in vitro lncRNA knockdown in C2C12
      cells. Network analysis suggested a central role for lncRNAs in modulating
      NFkappaB- and CREB1-regulated genes during embryonic heart growth and identified
      multiple mRNAs within these pathways that are also regulated, but independently
      of lncRNAs. 

PMID- 25071213
TI  - Threonine-4 of the budding yeast RNAP II CTD couples transcription with Htz1
      mediated chromatin remodeling.
AB  - The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAP II)
      consists of repeated YSPTSPS heptapeptides and connects transcription with
      cotranscriptional events. Threonine-4 (Thr4) of the CTD repeats has been shown to
      function in histone mRNA 3'-end processing in chicken cells and in
      transcriptional elongation in human cells. Here, we demonstrate that, in budding
      yeast, Thr4, although dispensable for growth in rich media, is essential in
      phosphate-depleted or galactose-containing media. Thr4 is required to maintain
      repression of phosphate-regulated (PHO) genes under normal growth conditions and
      for full induction of PHO5 and the galactose-induced GAL1 and GAL7 genes. We
      identify genetic links between Thr4 and the histone variant Htz1 and show that
      Thr4, as well as the Ino80 chromatin remodeler, is required for activation
      associated eviction of Htz1 specifically from promoters of the Thr4-dependent
      genes. Our study uncovers a connection between transcription and chromatin
      remodeling linked by Thr4 of the CTD. 

PMID- 25071215
TI  - Spatiotemporal control of epithelial remodeling by regulated myosin
      phosphorylation.
AB  - Spatiotemporally regulated actomyosin contractility generates the forces that
      drive epithelial cell rearrangements and tissue remodeling. Phosphorylation of
      the myosin II regulatory light chain (RLC) promotes the assembly of myosin
      monomers into active contractile filaments and is an essential mechanism
      regulating the level of myosin activity. However, the effects of phosphorylation
      on myosin localization, dynamics, and function during epithelial remodeling are
      not well understood. In Drosophila, planar polarized myosin contractility is
      required for oriented cell rearrangements during elongation of the body axis. We
      show that regulated myosin phosphorylation influences spatial and temporal
      properties of contractile behavior at molecular, cellular, and tissue length
      scales. Expression of myosin RLC variants that prevent or mimic phosphorylation
      both disrupt axis elongation, but have distinct effects at the molecular and
      cellular levels. Unphosphorylatable RLC produces fewer, slower cell
      rearrangements, whereas phosphomimetic RLC accelerates rearrangement and promotes
      higher-order cell interactions. Quantitative live imaging and biophysical
      approaches reveal that both phosphovariants reduce myosin planar polarity and
      mechanical anisotropy, altering the orientation of cell rearrangements during
      axis elongation. Moreover, the localized myosin activator Rho-kinase is required
      for spatially regulated myosin activity, even when the requirement for
      phosphorylation is bypassed by the expression of phosphomimetic myosin RLC. These
      results indicate that myosin phosphorylation influences both the level and the
      spatiotemporal regulation of myosin activity, linking molecular properties of
      myosin activity to tissue morphogenesis. 

PMID- 25071216
TI  - Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp
      loader to mediate efficient replication and virus persistence.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and
      persists as a multiple-copy, extrachromosomal, circular episome. To persist, the
      viral genome must replicate with each cell cycle. The KSHV latency-associated
      nuclear antigen (LANA) mediates viral DNA replication and persistence, but little
      is known regarding the underlying mechanisms. We find that LANA recruits
      replication factor C (RFC), the DNA polymerase clamp [proliferating cell nuclear
      antigen (PCNA)] loader, to drive DNA replication efficiently. Mutated LANA
      lacking RFC interaction was deficient for LANA-mediated DNA replication and
      episome persistence. RFC depletion had a negative impact on LANA's ability to
      replicate and maintain viral DNA in cells containing artificial KSHV episomes or
      in infected cells, leading to loss of virus. LANA substantially increased PCNA
      loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These
      findings suggest that PCNA loading is a rate-limiting step in DNA replication
      that is incompatible with viral survival. LANA enhancement of PCNA loading
      permits efficient virus replication and persistence, revealing a previously
      unidentified mechanism for KSHV latency. 

PMID- 25071217
TI  - Synthesis and folding of a mirror-image enzyme reveals ambidextrous chaperone
      activity.
AB  - Mirror-image proteins (composed of D-amino acids) are promising therapeutic
      agents and drug discovery tools, but as synthesis of larger D-proteins becomes
      feasible, a major anticipated challenge is the folding of these proteins into
      their active conformations. In vivo, many large and/or complex proteins require
      chaperones like GroEL/ES to prevent misfolding and produce functional protein.
      The ability of chaperones to fold D-proteins is unknown. Here we examine the
      ability of GroEL/ES to fold a synthetic d-protein. We report the total chemical
      synthesis of a 312-residue GroEL/ES-dependent protein, DapA, in both L- and D
      chiralities, the longest fully synthetic proteins yet reported. Impressively,
      GroEL/ES folds both L- and D-DapA. This work extends the limits of chemical
      protein synthesis, reveals ambidextrous GroEL/ES folding activity, and provides a
      valuable tool to fold d-proteins for drug development and mirror-image synthetic
      biology applications.

PMID- 25071218
TI  - UV-B detected by the UVR8 photoreceptor antagonizes auxin signaling and plant
      shade avoidance.
AB  - Plants detect different facets of their radiation environment via specific
      photoreceptors to modulate growth and development. UV-B is perceived by the
      photoreceptor UV RESISTANCE LOCUS 8 (UVR8). The molecular mechanisms linking UVR8
      activation to plant growth are not fully understood, however. When grown in close
      proximity to neighboring vegetation, shade-intolerant plants initiate dramatic
      stem elongation to overtop competitors. Here we show that UV-B, detected by UVR8,
      provides an unambiguous sunlight signal that inhibits shade avoidance responses
      in Arabidopsis thaliana by antagonizing the phytohormones auxin and gibberellin.
      UV-B triggers degradation of the transcription factors PHYTOCHROME INTERACTING
      FACTOR 4 and PHYTOCHROME INTERACTING FACTOR 5 and stabilizes growth-repressing
      DELLA proteins, inhibiting auxin biosynthesis via a dual mechanism. Our findings
      show that UVR8 signaling is closely integrated with other photoreceptor pathways
      to regulate auxin signaling and plant growth in sunlight. 

PMID- 25071219
TI  - Photoreceptor partner FHY1 has an independent role in gene modulation and plant
      development under far-red light.
AB  - To incorporate the far-red light (FR) signal into a strategy for optimizing plant
      growth, FAR-RED ELONGATED HYPOCOTYL1 (FHY1) mediates the nuclear translocation of
      the FR photoreceptor phytochrome A (phyA) and facilitates the association of phyA
      with the promoters of numerous associated genes crucial for the response to
      environmental stimuli. However, whether FHY1 plays additional roles after FR
      irradiation remains elusive. Here, through the global identification of FHY1
      chromatin association sites through ChIP-seq analysis and by the comparison of
      FHY1-associated sites with phyA-associated sites, we demonstrated that nuclear
      FHY1 can either act independently of phyA or act in association with phyA to
      activate the expression of distinct target genes. We also determined that phyA
      can act independently of FHY1 in regulating phyA-specific target genes.
      Furthermore, we determined that the independent FHY1 nuclear pathway is involved
      in crucial aspects of plant development, as in the case of inhibited seed
      germination under FR during salt stress. Notably, the differential presence of
      cis-elements and transcription factors in common and unique FHY1- and/or phyA
      associated genes are indicative of the complexity of the independent and
      coordinated FHY1 and phyA pathways. Our study uncovers previously unidentified
      aspects of FHY1 function beyond its currently recognized role in phyA-dependent
      photomorphogenesis. 

PMID- 25071220
TI  - Prehistoric deforestation at Chaco Canyon?
AB  - Ancient societies are often used to illustrate the potential problems stemming
      from unsustainable land-use practices because the past seems rife with examples
      of sociopolitical "collapse" associated with the exhaustion of finite resources.
      Just as frequently, and typically in response to such presentations,
      archaeologists and other specialists caution against seeking simple cause-and
      effect-relationships in the complex data that comprise the archaeological record.
      In this study we examine the famous case of Chaco Canyon, New Mexico, during the
      Bonito Phase (ca. AD 860-1140), which has become a prominent popular illustration
      of ecological and social catastrophe attributed to deforestation. We conclude
      that there is no substantive evidence for deforestation at Chaco and no obvious
      indications that the depopulation of the canyon in the 13th century was caused by
      any specific cultural practices or natural events. Clearly there was a reason why
      these farming people eventually moved elsewhere, but the archaeological record
      has not yet produced compelling empirical evidence for what that reason might
      have been. Until such evidence appears, the legacy of Ancestral Pueblo society in
      Chaco should not be used as a cautionary story about socioeconomic failures in
      the modern world. 

PMID- 25071222
TI  - Deficiencies in both starch synthase IIIa and branching enzyme IIb lead to a
      significant increase in amylose in SSIIa-inactive japonica rice seeds.
AB  - Starch synthase (SS) IIIa has the second highest activity of the total soluble SS
      activity in developing rice endosperm. Branching enzyme (BE) IIb is the major BE
      isozyme, and is strongly expressed in developing rice endosperm. A mutant
      (ss3a/be2b) was generated from wild-type japonica rice which lacks SSIIa
      activity. The seed weight of ss3a/be2b was 74-94% of that of the wild type,
      whereas the be2b seed weight was 59-73% of that of the wild type. There were
      significantly fewer amylopectin short chains [degree of polymerization (DP) <=13]
      in ss3a/be2b compared with the wild type. In contrast, the amount of long chains
      (DP >=25) connecting clusters of amylopectin in ss3a/be2b was higher than in the
      wild type and lower than in be2b. The apparent amylose content of ss3a/be2b was
      45%, which was >1.5 times greater than that of either ss3a or be2b. Both SSIIIa
      and BEIIb deficiencies led to higher activity of ADP-glucose pyrophosphorylase
      (AGPase) and granule-bound starch synthase I (GBSSI), which partly explains the
      high amylose content in the ss3a/be2b endosperm. The percentage apparent amylose
      content of ss3a and ss3a/be2b at 10 days after flowering (DAF) was higher than
      that of the wild type and be2b. At 20 DAF, amylopectin biosynthesis in be2b and
      ss3a/be2b was not observed, whereas amylose biosynthesis in these lines was
      accelerated at 30 DAF. These data suggest that the high amylose content in the
      ss3a/be2b mutant results from higher amylose biosynthesis at two stages, up to 20
      DAF and from 30 DAF to maturity.

PMID- 25071221
TI  - An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the
      target gene of SiAREB, plays a critical role under drought stress.
AB  - The DREB (dehydration-responsive element binding)-type transcription factors
      regulate the expression of stress-inducible genes by binding the DRE/CRT cis
      elements in promoter regions. The upstream transcription factors that regulate
      the transcription of DREB transcription factors have not been clearly defined,
      although the function of DREB transcription factors in abiotic stress is known.
      In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene
      (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level
      of SiARDP increased not only after drought, high salt, and low temperature
      stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA
      responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of
      SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)
      type transcription factors, SiAREB1 and SiAREB2, could physically bind to the
      ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in
      Arabidopsis thaliana enhanced drought and salt tolerance during seed germination
      and seedling development, and overexpression of SiARDP in foxtail millet improved
      drought tolerance. The expression levels of target genes of SiARDP were
      upregulated in transgenic Arabidopsis and foxtail millet. These results reveal
      that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent
      signal pathways and plays a critical role in the abiotic stress response in
      plants.

PMID- 25071224
TI  - Effect of various sources and levels of iodine, as well as the kind of diet, on
      the performance of young laying hens, iodine accumulation in eggs, egg
      characteristics, and morphotic and biochemical indices in blood.
AB  - Young hens were fed over a period of 150 d with 2 kinds of diets including corn
      and soybean meal or corn, soybean, and rapeseed meal. Diets were enriched with
      potassium iodide (KI) or potassium iodate (KIO3) as an I source in amounts equal
      to 1, 3, or 5 mg of supplemented I/kg of feed. The hen performance, egg quality,
      hematological and morphotic indices in blood, hepatic enzyme activity, lipid
      indices in blood serum as well as I accumulation in wet egg content were
      determined. Introduction of 00-variety rapeseed meal into the diet improved the
      laying rate and feed conversion (P < 0.05); however, better egg weight was noted
      by feeding the hens with a diet without rapeseed meal. Use of KI as an I source
      enhanced the egg weight. The increased I level in the diet had an equivocal
      influence on egg weight, improved the feed conversion per 1 kg of eggs, and
      decreased the proportion of damaged eggs. The use of corn, soybean, and rapeseed
      meal in hen diets significantly improved yolk color; similar results were noted
      after an increase in I levels in the diets after 3 mo of feeding. Hematological
      indices of hen blood demonstrated significantly higher red blood cells numbers
      and hemoglobin concentrations with the use of KI. The use of a diet containing
      rapeseed meal led to an enhancement of hepatic enzyme activity, especially of
      alkaline phosphatase (P = 0.007). Lipid metabolism indices were not influenced by
      the kind of diet or the I source or level. The accumulation of I in wet egg
      content was negatively influenced by the use of a diet containing rapeseed meal
      (P = 0.000). The application of KI as an I source enhanced (P = 0.003) the
      accretion of I in eggs after 5 mo of treatment. Enhanced I supply significantly
      increased accumulation of I in eggs (P = 0.000) after 3 and 5 mo of the
      experiment from 260 and 310 to 1,011 and 1,256 ug/kg of wet egg content,
      respectively. 

PMID- 25071225
TI  - Short-term effects of lower oil dried distillers grains with solubles in laying
      hen rations.
AB  - Extraction of oil from dried distillers grains has become a common practice among
      US ethanol producers. The valuable oil has been diverted to markets other than
      poultry feed, leaving new dried distillers grains with solubles (DDGS) products
      higher in fiber and purportedly lower in ME. This study compared 3 DDGS products
      with 10.3, 7.3, or 5.2% ether extract, respectively, with a corn-soy control
      ration in young Bovan laying hens for a feeding period from 20 to 33 wk of age.
      The DDGS was fed at the rate of 20% of the ration. Lower oil content of DDGS had
      no effect on short-term egg production parameters: feed intake, egg production,
      egg weight or mass, and hen weight gain. The diets containing lower fat DDGS
      (5.2%) did have reduced AME and kilocalories per day intake for laying hens. For
      each percent reduction in oil from a normal DDGS sample (10.3%) to medium oil
      (7.3%) DDGS, AME decreased 42.3 kcal/kg of diet. However, total kilocalories per
      day intake did sustain good egg production during this short trial. 

PMID- 25071223
TI  - A novel rice C2H2-type zinc finger protein, ZFP36, is a key player involved in
      abscisic acid-induced antioxidant defence and oxidative stress tolerance in rice.
AB  - C2H2-type zinc finger proteins (ZFPs) have been shown to play important roles in
      the responses of plants to oxidative and abiotic stresses, and different members
      of this family might have different roles during stresses. Here a novel abscisic
      acid (ABA)- and hydrogen peroxide (H2O2)-responsive C2H2-type ZFP gene, ZFP36, is
      identified in rice. The analyses of ZFP36-overexpressing and silenced transgenic
      rice plants showed that ZFP36 is involved in ABA-induced up-regulation of the
      expression and the activities of superoxide dismutase (SOD) and ascorbate
      peroxidase (APX). Overexpression of ZFP36 in rice plants was found to elevate the
      activities of antioxidant enzymes and to enhance the tolerance of rice plants to
      water stress and oxidative stress. In contrast, an RNA interference (RNAi) mutant
      of ZFP36 had lower activities of antioxidant enzymes and was more sensitive to
      water stress and oxidative stress. ABA-induced H2O2 production and ABA-activated
      mitogen-activated protein kinases (MAPKs) were shown to regulate the expression
      of ZFP36 in ABA signalling. On the other hand, ZFP36 also regulated the
      expression of NADPH oxidase genes, the production of H2O2, and the expression of
      OsMPK genes in ABA signalling. These results indicate that ZFP36 is required for
      ABA-induced antioxidant defence, for the tolerance of rice plants to water stress
      and oxidative stress, and for the regulation of the cross-talk between NADPH
      oxidase, H2O2, and MAPK in ABA signalling.

PMID- 25071226
TI  - Different sources of maternal selenium affect selenium retention, antioxidant
      status, and meat quality of 56-day-old offspring of broiler breeders.
AB  - The maternal effect of different Se source in offspring of young broiler breeders
      has been reported, but the lasting maternal effect of different sources of Se on
      offspring of breeders has received limited attention, so this study was conducted
      to investigate the effects of different maternal Se sources on Se retention,
      antioxidant status, and meat quality of 56-d-old offspring of broiler breeders. A
      total of two hundred forty 39-wk-old Lingnan Yellow broiler breeders were
      randomly distributed into 2 treatments, each of which was replicated 3 times with
      40 birds per replicate, with a 14-d pretreatment and 56-d trial period. The
      treatments were fed a basal corn-soybean diet (0.04 mg?kg-1 Se) supplemented with
      0.3 mg?kg-1 sodium selenite (SS) or selenomethionine (Se-Met). Fertile eggs were
      collected for incubation, after which 180 healthy chicks from each treatment were
      selected and randomly allocated into 3 replicates, with 60 birds per replicate.
      All the chicks were fed the same basal diet (0.04 mg?kg-1 Se) for 56 d. The Se
      concentrations in serum and tissues (liver, kidney, and breast muscle) of the 56
      d-old offspring were significantly (P < 0.01) increased by maternal Se-Met intake
      compared with maternal SS intake. The antioxidant status of the 56-d-old
      offspring was greatly improved by maternal Se-Met supplementation in contrast
      with maternal SS supplementation, which was shown by increased glutathione
      peroxidase activity in serum and breast muscle (P < 0.01), glutathione
      concentration in serum (P < 0.05), and total antioxidant capability in pancreas
      (P < 0.01), as well as cytosolic glutathione peroxidase mRNA abundance in breast
      muscle, liver (P < 0.01), and pancreas (P < 0.05). The maternal Se-Met treatment
      was more effective in maintaining the shape of liver and pancreas cells, cell
      nuclei, chromatin, as well as cell membrane structure, and more organelles were
      observed in liver cells. The maternal Se-Met treatment had significant (P < 0.05)
      reduced the 48-h drip loss of 56-d-old offspring in comparison with maternal SS
      treatment. The results suggest that maternal Se-Met diet is superior to maternal
      SS diet in increasing Se retention and improving antioxidant status and meat
      quality of 56-d-old offspring.

PMID- 25071227
TI  - Performance of an image analysis processing system for hen tracking in an
      environmental preference chamber.
AB  - Image processing systems have been widely used in monitoring livestock for many
      applications, including identification, tracking, behavior analysis, occupancy
      rates, and activity calculations. The primary goal of this work was to quantify
      image processing performance when monitoring laying hens by comparing length of
      stay in each compartment as detected by the image processing system with the
      actual occurrences registered by human observations. In this work, an image
      processing system was implemented and evaluated for use in an environmental
      animal preference chamber to detect hen navigation between 4 compartments of the
      chamber. One camera was installed above each compartment to produce top-view
      images of the whole compartment. An ellipse-fitting model was applied to captured
      images to detect whether the hen was present in a compartment. During a choice
      test study, mean +/- SD success detection rates of 95.9 +/- 2.6% were achieved
      when considering total duration of compartment occupancy. These results suggest
      that the image processing system is currently suitable for determining the
      response measures for assessing environmental choices. Moreover, the image
      processing system offered a comprehensive analysis of occupancy while
      substantially reducing data processing time compared with the time-intensive
      alternative of manual video analysis. The above technique was used to monitor
      ammonia aversion in the chamber. As a preliminary pilot study, different levels
      of ammonia were applied to different compartments while hens were allowed to
      navigate between compartments. Using the automated monitor tool to assess
      occupancy, a negative trend of compartment occupancy with ammonia level was
      revealed, though further examination is needed. 

PMID- 25071228
TI  - Effects of trypsin inhibitor and particle size of expeller-extracted soybean meal
      on broiler live performance and weight of gizzard and pancreas.
AB  - Soybean meal (SBM) is a co-product that remains after the oil is removed from
      whole soybeans by either solvent extraction or mechanically pressing soybeans
      using an expeller. Expeller-extracted soybean meal (ESBM) contains more fat and
      less protein than solvent-extracted soybean meal (SSBM), but has higher trypsin
      inhibitors (TI) that limit its inclusion in poultry diets. We hypothesized that
      increasing the particle size of ESBM could enhance chick tolerance to dietary TI.
      The experiment consisted of a 2 * 6 factorial arrangement of 2 ESBM particle
      sizes (coarse, 1,300 um, and fine, 530 um) and 6 TI levels (6, 9, 12, 15, 18, and
      21 TIU/mg). A total of 672 male broiler chicks was randomly assigned among the 12
      treatment combinations with 8 replicates per combination. The birds were provided
      with 1 kg/bird of starter diet in a crumble form. The pancreas and gizzard were
      excised and weighed at 16 d of age and organ weights relative to BW calculated.
      Feed consumption, BW, and feed conversion ratio (FCR) were determined at 7 and 14
      d of age. Increasing TI level produced a quadratic effect (P < 0.01) on BW and
      FCR at 14 d of age. The best performance was obtained when chicks were fed diets
      containing ESBM at intermediate TI levels. Increasing the particle size of the
      ESBM from 530 to 1,300 um improved BW and feed intake (P < 0.01) without
      affecting FCR. The relative weight of the pancreas increased linearly as TI level
      increased (P < 0.001). The results of this study indicated that chicks performed
      better when fed coarse ESBM at an intermediate TI level. 

PMID- 25071229
TI  - Contribution of protein, starch, and fat to the apparent ileal digestible energy
      of corn- and wheat-based broiler diets in response to exogenous xylanase and
      amylase without or with protease.
AB  - The ileal energy contribution of protein, starch, and fat in response to 2
      exogenous enzyme combinations was studied in 2 digestibility assays with 21-
      (experiment 1; 432 birds) and 42-d-old (experiment 2; 288 birds) Ross 308 broiler
      chickens. A 2 * 2 * 3 factorial arrangement of treatments with 2 base grains
      (corn or wheat), without or with high fiber ingredients (corn distillers dried
      grains with solubles and canola meal), and 3 enzyme treatments was implemented.
      Enzyme treatments, fed from 12 to 21 d or 32 to 42 d, were 1) without enzymes, 2)
      with xylanase from Trichoderma ressei (2,000 U/kg) and amylase from Bacillus
      licheniformis (200 U/kg; XA), or 3) with XA plus protease from Bacillus subtilis
      (4,000 U/kg; XAP). All diets contained Escherichia coli phytase (500 FTU/kg).
      Apparent ileal digestibility (AID) of protein, starch, and fat, as well as the
      apparent ileal digestible energy, were determined using titanium dioxide as inert
      marker. A generalized mixed model was used to test main effects and 2-way
      interactions at P < 0.05. An enzyme * grain interaction was detected for AID of
      starch at 21 and 42 d, and AID of fat at 21 d, with greater effects of enzymes in
      wheat-based compared with corn-based diets, but significant increments due to
      enzymes compared with controls in both diet types. Apparent ileal digestibility
      of fat at 42 d increased with enzyme supplementation compared with the control
      treatments. The XA and XAP treatments gradually (P < 0.05) increased AID of
      protein at 21 d, but only XAP increased AID of protein compared with the control
      at 42 d. Compared with the controls, XA increased AID energy by 52 or 87 kcal,
      and XAP by 104 or 152 kcal/kg of DM at 21 or 42 d, respectively. The caloric
      contribution of starch, fat, and protein were affected differentially by base
      grain and the presence of fibrous ingredients at 21 and 42 d of age. 

PMID- 25071230
TI  - Effect of Origanum chemotypes on broiler intestinal bacteria.
AB  - Essential oils have been proposed as alternatives to antibiotic use in food
      animal production. This study evaluated 3 chemotypes of the Origanum genus,
      containing varying amounts of secondary metabolites carvacrol, thymol, and
      sabinene, in the broiler chicken diet. Aerial parts of Origanum vulgare L. (OL),
      O. vulgare L. ssp. hirtum (OH), and O. majorana (OM) were collected from a
      greenhouse located in the high altitude Sabana de Bogota (Savanna of Bogota) and
      O. vulgare L. ssp. hirtum (OG) produced and ground in Greece. Oregano essential
      oils (OEO) from these plants were obtained by steam distillation and analyzed by
      gas chromatography coupled to a mass spectrometer. Six treatments were evaluated:
      200 mg/kg of OEO from OH, OL, and OM, 50 mg/kg of OEO from OG, 500 mg/kg of
      chlortetracycline, and without additives. Broiler chicks were maintained at 2,600
      m above sea level, placed in brooder cages under a completely randomized design.
      Template DNA was isolated from duodenal, jejunal, ileal, and cecal contents in
      each group and bacterial 16S rDNA patterns were analyzed by denaturing gradient
      gel electrophoresis. Dendrograms of denaturing gradient gel electrophoresis band
      patterns revealed 2 main clusters, OEO-treated chicks and nontreated control
      chicks, in each intestinal segment. Band patterns from different gut compartments
      revealed major bacterial population shifts in the foregut (duodenum, jejunum, and
      ileum) compared with the hindgut (cecum and colon) at all ages evaluated (P <
      0.05). The OEO groups showed less shift (62.7% similarity coefficient) between
      these 2 compartments versus the control groups (53.7% similarity coefficient). A
      reduction of 59% in mortality from ascites was seen in additive-supplemented
      groups compared with the control group. This study represents the first work to
      evaluate the effects of the 3 main chemotypes of Origanum genus in broilers. 

PMID- 25071231
TI  - Effects of moment of hatch and feed access on chicken development.
AB  - The current study evaluated effects of hatch moment and immediate feed and water
      access within a 24-h hatch window on chicken growth and development. Five hundred
      four male chickens obtained from a 49-wk-old Ross 308 breeder flock were assigned
      to 72 cages based on hatching moment (early, midterm, or late; selected during
      periods of 475 to 481, 483 to 487, and 489 to 493 h after onset of incubation).
      At the end of each hatching period, chickens were moved to the grow-out facility
      and one-half of the chickens received feed and water ad libitum immediately.
      Remaining chickens received feed and water from 504 h after onset of incubation
      (d 0). Body weight gain and feed intake for each cage were recorded at d 0, 1, 4,
      7, 11, and 18. Chickens were sampled at d 4 and 18 for organ and carcass
      development. Early hatchers had lower BW at placement compared with midterm and
      late hatchers but compensated for this afterward, resulting in a higher BW at d 4
      (112.8, 107.1, and 103.3 g, respectively). From d 0 to 18, early hatchers tended
      to have higher BW gain than both other groups. Relative breast meat yield at d
      18, expressed as percentage of carcass weight, was higher for early (30.4%) than
      midterm (28.5%) and late hatchers (27.8%). Up to d 7, direct feed access resulted
      in higher BW gain (6.1%) and feed intake (4.2%) compared with delayed feed
      access. No effect of moment of feed access on feed efficiency or organ weights
      was found. Direct feed access resulted in a higher weight:length ratio of the
      jejunum (12.5%) and ileum (7.5%) at d 4 compared with delayed feed access. These
      results suggest that early hatchers have a different developmental and growth
      pattern than midterm or late hatchers within a 24-h hatch window. A mild delay in
      feed access after hatch affects growth and development during the first week
      after hatch. 

PMID- 25071232
TI  - Beyond Hopkinson's bar.
AB  - In order to perform experimental identification of high strain rate material
      models, engineers have only a very limited toolbox based on test procedures
      developed decades ago. The best example is the so-called split Hopkinson pressure
      bar based on the bar concept introduced 100 years ago by Bertram Hopkinson to
      measure blast pulses. The recent advent of full-field deformation measurements
      using imaging techniques has allowed novel approaches to be developed and
      exciting new testing procedures to be imagined for the first time. One can use
      this full-field information in conjunction with efficient numerical inverse
      identification tools such as the virtual fields method (VFM) to identify material
      parameters at high rates. The underpinning novelty is to exploit the inertial
      effects developed in high strain rate loading. This paper presents results from a
      new inertial impact test to obtain stress-strain curves at high strain rates
      (here, up to 3000 s(-1)). A quasi-isotropic composite specimen is equipped with a
      grid and images are recorded with the new HPV-X camera from Shimadzu at 5 Mfps
      and the SIMX16 camera from Specialised Imaging at 1 Mfps. Deformation, strain and
      acceleration fields are then input into the VFM to identify the stiffness
      parameters with unprecedented quality. 

PMID- 25071233
TI  - Propagation of short stress pulses in discrete strongly nonlinear tunable
      metamaterials.
AB  - The propagation of short pulses with wavelength comparable to the size of a unit
      cell has been studied in a one-dimensional discrete metamaterial composed of
      steel discs alternating with toroidal nitrile O-rings under different levels of
      precompression using experiments, numerical simulations and theoretical analysis.
      This strongly nonlinear metamaterial is more tunable than granular chains
      composed of linear elastic spherical particles and has better potential for
      attenuation of dynamic loads. A double power-law relationship for compressed O
      rings was found to describe adequately their quasi-static and dynamic behaviour
      with significantly different elastic moduli. It is demonstrated that the double
      power-law metamaterial investigated allows a dramatic increase in sound speed and
      acoustic impedance of three to four times using a moderate force. 

PMID- 25071234
TI  - Survival of fossils under extreme shocks induced by hypervelocity impacts.
AB  - Experimental data are shown for survival of fossilized diatoms undergoing shocks
      in the GPa range. The results were obtained from hypervelocity impact experiments
      which fired fossilized diatoms frozen in ice into water targets. After the shots,
      the material recovered from the target water was inspected for diatom fossils.
      Nine shots were carried out, at speeds from 0.388 to 5.34 km s(-1), corresponding
      to mean peak pressures of 0.2-19 GPa. In all cases, fragmented fossilized diatoms
      were recovered, but both the mean and the maximum fragment size decreased with
      increasing impact speed and hence peak pressure. Examples of intact diatoms were
      found after the impacts, even in some of the higher speed shots, but their
      frequency and size decreased significantly at the higher speeds. This is the
      first demonstration that fossils can survive and be transferred from projectile
      to target in hypervelocity impacts, implying that it is possible that, as
      suggested by other authors, terrestrial rocks ejected from the Earth by giant
      impacts from space, and which then strike the Moon, may successfully transfer
      terrestrial fossils to the Moon. 

PMID- 25071235
TI  - Improved specimen recovery in tensile split Hopkinson bar.
AB  - This paper presents an improved specimen recovery method for the tensile split
      Hopkinson bar (TSHB) technique. The method is based on the trapping of residual
      stress waves with the use of momentum trap bars. As is well known, successful
      momentum trapping in TSHB is highly sensitive to experimental uncertainties,
      especially on the incident bar side of the set-up. However, as is demonstrated in
      this paper, significant improvement in the reliability of specimen recovery is
      obtained by using two momentum trap bars in contact with the incident bar. This
      makes the trapping of the reflected wave insensitive to striker speed and removes
      the need for a precision set gap between the incident bar and the momentum trap. 

PMID- 25071236
TI  - On backward dispersion correction of Hopkinson pressure bar signals.
AB  - Elastic theory shows that wide spectrum signals in the Hopkinson pressure bar
      suffer two forms of distortion as they propagate from the loaded bar face. These
      must be accounted for if accurate determination of the impact load is to be
      possible. The first form of distortion is the well-known phase velocity
      dispersion effect. The second form, which can be equally deleterious, is the
      prediction that at high frequencies, the stress and strain generated in the bar
      varies with radial position on the cross section, even for a uniformly applied
      loading. We consider the consequences of these effects on our ability to conduct
      accurate backward dispersion correction of bar signals, that is, to derive the
      impact face load from the dispersed signal recorded at some other point on the
      bar. We conclude that there is an upper limit on the frequency for which the
      distortion effects can be accurately compensated, and that this can significantly
      affect the accuracy of experimental results. We propose a combination of
      experimental studies and detailed numerical modelling of the impact event and
      wave propagation along the bar to gain better understanding of the frequency
      content of the impact event, and help assess the accuracy of experimental
      predictions of impact face load. 

PMID- 25071237
TI  - Experimental and numerical investigations on the use of polymer Hopkinson
      pressure bars.
AB  - Split Hopkinson pressure bar (SHPB) testing has traditionally been carried out
      using metal bars. For testing low stiffness materials such as rubbers or low
      strength materials such as low density cellular solids considered primarily
      herein, there are many advantages to replacing the metal bars with polymer bars.
      An investigation of a number of aspects associated with the accuracy of SHPB
      testing of these materials is reported. Test data are used to provide qualitative
      comparisons of accuracy using different bar materials and wave-separation
      techniques. Sample results from SHPB tests are provided for balsa, Rohacell foam
      and hydroxyl-terminated polybutadiene. The techniques used are verified by finite
      element (FE) analysis. Experimentally, the material properties of the bars are
      determined from impact tests in the form of a complex elastic modulus without
      curve fitting to a rheological model. For the simulations, a rheological model is
      used to define the bar properties by curve fitting to the experimentally derived
      properties. Wave propagation in a polymer bar owing to axial impact of a steel
      bearing ball is simulated. The results indicate that the strain histories can be
      used to determine accurately the viscoelastic properties of polymer bars. An FE
      model of the full viscoelastic SHPB set-up is then used to simulate tests on
      hyperelastic materials. 

PMID- 25071238
TI  - Using the split Hopkinson pressure bar to validate material models.
AB  - This paper gives a discussion of the use of the split-Hopkinson bar with
      particular reference to the requirements of materials modelling at QinetiQ. This
      is to deploy validated material models for numerical simulations that are
      physically based and have as little characterization overhead as possible. In
      order to have confidence that the models have a wide range of applicability, this
      means, at most, characterizing the models at low rate and then validating them at
      high rate. The split Hopkinson pressure bar (SHPB) is ideal for this purpose. It
      is also a very useful tool for analysing material behaviour under non-shock wave
      loading. This means understanding the output of the test and developing
      techniques for reliable comparison of simulations with SHPB data. For materials
      other than metals comparison with an output stress v strain curve is not
      sufficient as the assumptions built into the classical analysis are generally
      violated. The method described in this paper compares the simulations with as
      much validation data as can be derived from deployed instrumentation including
      the raw strain gauge data on the input and output bars, which avoids any
      assumptions about stress equilibrium. One has to take into account Pochhammer
      Chree oscillations and their effect on the specimen and recognize that this is
      itself also a valuable validation test of the material model. 

PMID- 25071239
TI  - The use of the direct impact Hopkinson pressure bar technique to describe
      thermally activated and viscous regimes of metallic materials.
AB  - The influence of strain rate over domains involving the thermal activation and
      the viscous drag behaviour of the dislocations is discussed. While it is
      recognized that the Koslky-Hopkinson technique or split Hopkinson pressure bar
      technique can generate data up to the upper strain-rate limit of the thermal
      activated regime, it is necessary to use a direct impact Hopkinson pressure bar
      technique to access the viscous regime. Data generated with this technique are
      presented for a series of metals, including steel, nickel, copper and tungsten
      alloys. The motivation to generate such data is provided through three industrial
      applications. 

PMID- 25071240
TI  - The shock and spall response of three industrially important hexagonal close
      packed metals: magnesium, titanium and zirconium.
AB  - Magnesium, titanium and zirconium and their alloys are extensively used in
      industrial and military applications where they would be subjected to extreme
      environments of high stress and strain-rate loading. Their hexagonal close-packed
      (HCP) crystal lattice structures present interesting challenges for optimizing
      their mechanical response under such loading conditions. In this paper, we review
      how these materials respond to shock loading via plate-impact experiments. We
      also discuss the relationship between a heterogeneous and anisotropic
      microstructure, typical of HCP materials, and the directional dependency of the
      elastic limit and, in some cases, the strength prior to failure. 

PMID- 25071241
TI  - Impact compressive and bending behaviour of rocks accompanied by electromagnetic
      phenomena.
AB  - It is well known that electromagnetic phenomena are often observed preceding
      earthquakes. However, the mechanism by which these electromagnetic waves are
      generated during the fracture and deformation of rocks has not been fully
      identified. Therefore, in order to examine the relationship between the
      electromagnetic phenomena and the mechanical properties of rocks, uniaxial
      compression and three-point bending tests for two kinds of rocks with different
      quartz content, granite and gabbro, have been carried out at quasi-static and
      dynamic rates. Especially, in the bending tests, pre-cracked specimens of granite
      were also tested. Using a split Hopkinson pressure bar and a ferrite-core antenna
      in close proximity to the specimens, both the stress-strain (load-displacement)
      curve and simultaneous electromagnetic wave magnitude were measured. It was found
      that the dynamic compressive and bending strengths and the stress increase slope
      of both rocks were higher than those observed in static tests; therefore, there
      is a strain-rate dependence in their strength and stress increase rate. It was
      found from the tests using the pre-cracked bending specimens that the intensity
      of electromagnetic waves measured during crack extension increased almost
      proportionally to the increase of the maximum stress intensity factor of
      specimens. This tendency was observed in both the dynamic and quasi-static three
      point bending tests for granite. 

PMID- 25071242
TI  - Towards a shock tube method for the dynamic calibration of pressure sensors.
AB  - In theory, shock tubes provide a pressure change with a very fast rise time and
      calculable amplitude. This pressure step could provide the basis for the
      calibration of pressure transducers used in highly dynamic applications. However,
      conventional metal shock tubes can be expensive, unwieldy and difficult to
      modify. We describe the development of a 1.4 MPa (maximum pressure) shock tube
      made from unplasticized polyvinyl chloride pressure tubing which provides a low
      cost, light and easily modifiable basis for establishing a method for determining
      the dynamic characteristics of pressure sensors. 

PMID- 25071243
TI  - Absorbing materials with applications in radiotherapy and radioprotection.
AB  - The radiotherapy centres are using linear accelerators equipped with multi-leaf
      collimators (MLCs) for treatments of various types of cancer. For superficial
      cancers located at a maximum depth of 3 cm high-energy electrons are often used,
      but MLC cannot be used together with electron applicators. Due to the fact that
      the tumour shape is not square (as electron applicators), searching for different
      materials that can be used as absorbents or shields for the protection of
      adjacent organs is of paramount importance. This study presents an experimental
      study regarding the transmitted dose through some laboratory-made materials when
      subjected to electron beams of various energies (ranging from 6 to 15 MeV). The
      investigated samples were composite materials consisting of silicon rubber and
      micrometre aluminium particles with different thicknesses and various mass
      fraction of aluminium. The measurements were performed at a source surface
      distance of 100 cm in the acrylic phantom. The experimental results show that the
      transmitted dose through tested samples is ranging between ~1.8 and 90%,
      depending on the electron beam energy, sample thickness and sample composition.
      These preliminary results suggest that the analysed materials can be used as
      absorbers or shields in different applications in radiotherapy and
      radioprotection.

PMID- 25071244
TI  - The patient as a radioactive source: an intercomparison of survey meters for
      measurements in nuclear medicine.
AB  - In this work, the radiation exposure in nuclear medicine is evaluated by
      measuring dose rates in the proximity of patients and those in close contact to
      sources like capsules and syringes. A huge number of different survey meters
      (SMs) are offered commercially. This topic has recently gained interest since
      dosemeters and active personal dosemeters (APD) for the new dose quantities
      (ambient and directional dose equivalent) have become available. One main concern
      is the practical use of SMs and APD in daily clinical routines. Therefore, the
      radiation field of four common radiopharmaceuticals containing (18)F, (90)Y,
      (99m)Tc and (131)I in radioactive sources or after application to the patient was
      determined. Measurements were carried out with different SMs and for several
      distances. Dose rates decline significantly with the distance to the patient, and
      with some restrictions, APD can be used as SMs. 

PMID- 25071245
TI  - Establishment of a method for 222Rn determination in water by low-level liquid
      scintillation counter.
AB  - A procedure for the determination of (222)Rn in environmental water samples using
      liquid scintillation counting (LSC) was performed. The (226)Ra content in the
      water was determined by gamma-ray spectroscopy. An application of this procedure
      to drinking water collected from a public drinking fountain in Vojvodina (Serbia)
      is presented, including calculations of the annual effective dose for ingestion
      and inhalation for adults. 

PMID- 25071246
TI  - Radiation protection, radioactive waste management and site monitoring at the
      nuclear scientific experimental and educational centre IRT-Sofia at INRNE-BAS.
AB  - This article identifies important components and describes the safe practices in
      implementing radiation protection and radioactive waste management programmes,
      and in their optimisation at the Nuclear Scientific Experimental and Educational
      Centre with research reactor IRT at INRNE-BAS. It covers the instrumentation and
      personal protective equipment and organisational issues related to the continuous
      site monitoring. The reactor is under major reconstruction and the measures
      applied to radiation monitoring of environment and working area focused on
      restricting the radiation exposure of the staff as well as compliance with
      international good practices related to the environmental and public radiation
      safety requirements are also addressed. 

PMID- 25071248
TI  - Human Papillomavirus Deoxyribonucleic Acid may not be Detected in Non-genital
      Benign Papillomatous Skin Lesions by Polymerase Chain Reaction.
AB  - BACKGROUND: Papillomatosis is a known histopathologic pattern usually seen in
      human papillomavirus (HPV) infection and verruca vulgaris is the typical example.
      This pattern is also detected in some other benign cutaneous lesions such as
      nevus sebaceous (NS), seborrheic keratosis (SK), trichilemmoma (TL) and inverted
      follicular keratosis (IFK). The association between papillomatous lesions and HPV
      infection is questionable. OBJECTIVE: The objective of this study was to
      investigate the presence of HPV deoxyribonucleic acid (DNA) in non-genital benign
      papillomatous skin lesions (NS, SK, TL and IFK) by polymerase chain reaction
      (PCR). MATERIALS AND METHODS: A total of 100 specimens of non-genital NS, SK, TL
      and IFK were retrieved from archives of Dermatopathology Department of Razi
      Hospital, between 2003 and 2010. The conventional PCR using consensus GP5+/GP6+
      primer and hydroxymethylbilane synthase gene as inner control was performed.
      RESULTS: PCR for HPV DNA revealed no positive results in any of 28 seborrheic
      keratosis (SK), 28 nevus sebaceous (NS), 28 inverted follicular keratosis (IFK)
      and 13 trichilemmoma (TL) studied specimens. CONCLUSION: Papillomatosis is
      usually a characteristic pattern of HPV infection. However, we found no
      association between HPV infection and non-genital benign papillomatous lesions.

PMID- 25071247
TI  - Nail psoriasis: the journey so far.
AB  - Nail involvement is an extremely common feature of psoriasis and affects
      approximately 10-78% of psoriasis patients with 5-10% of patients having isolated
      nail psoriasis. However, it is often an overlooked feature in the management of
      nail psoriasis, despite the significant burden it places on the patients as a
      result of functional impairment of manual dexterity, pain, and psychological
      stress. Affected nail plates often thicken and crumble, and because they are very
      visible, patients tend to avoid normal day-to-day activities and social
      interactions. Importantly, 70-80% of patients with psoriatic arthritis have nail
      psoriasis. In this overview, we review the clinical manifestations of psoriasis
      affecting the nails, the common differential diagnosis of nail psoriasis, Nail
      Psoriasis Severity Index and the various diagnostic aids for diagnosing nail
      psoriasis especially, the cases with isolated nail involvement. We have also
      discussed the available treatment options, including the topical, physical,
      systemic, and biological modalities, in great detail in order to equip the
      present day dermatologist in dealing with a big clinical challenge, that is,
      management of nail psoriasis. 

PMID- 25071249
TI  - Correlation between skin color evaluation by skin color scale chart and
      narrowband reflectance spectrophotometer.
AB  - CONTEXT: Various methods are available for the evaluation of skin color. A skin
      color scale chart is a convenient and inexpensive tool. However, the correlation
      between a skin color scale chart and objective measurement has not been
      evaluated. AIMS: To assess the correlation between skin color evaluation done by
      a skin color scale chart (Felix von Luschan skin color chart) and a narrowband
      reflectance spectrophotometer (Mexameter MX18). MATERIALS AND METHODS: The
      participants were evaluated for skin color by using the Felix von Luschan skin
      color chart (range 1-36) and a narrowband reflectance spectrophotometer
      (Mexameter MX18) in which the results of the measurements were expressed as
      Erythema (E) and Melanin (M) indices. Skin color was measured on four different
      anatomical skin sites from each participant on the medial aspect of the volar and
      the dorsal regions of both forearms. RESULTS: A total of 208 records from 52
      participants were established. The majority of participants (19.2%) were rated
      with the skin color scale at the number 16 (range 14-33). The mean M plus E, M,
      and E indices were 498.9 +/- 143.9, 230.4 +/- 74.4, and 268.5 +/- 73.2,
      respectively. The correlation coefficient between the number on the skin color
      scale and each index: M plus E, M, and E indices were 0.90, 0.90, and 0.86,
      respectively, with a statistical significance of P < 0.001. CONCLUSIONS: Skin
      color evaluation using a skin color scale chart has shown a high correlation with
      skin color evaluation done by the narrowband reflectance spectrophotometer.

PMID- 25071250
TI  - Predominant palmoplantar lichen planus: a diagnostic challenge.
AB  - BACKGROUND: Palmoplantar lesions in lichen planus (LP) are uncommon. In such
      cases, diagnosis is usually missed. This study was conducted to document various
      clinical and histopathological features of palmoplantar LP. MATERIALS AND
      METHODS: A total of 18 patients from our outpatient department with lesions of
      LP, either predominantly or exclusively on palms and/or soles were studied.
      Patients with history of drug intake in recent past and patients with classical
      acute widespread LP with a few lesions on palms or soles were excluded. In each
      patient, diagnosis was made on clinicopathological correlation. Various clinical
      and histopathological features were analyzed. RESULTS: Average age of onset was
      38 years. Male: female ratio was 1:0.6 and average disease duration was 11
      months. Exclusive palm or sole involvement was seen in 4/18 patients. Itching was
      the most common symptom. Clinically the most common variant was hypertrophic.
      Histologically presence of parakeratosis, spongiosis, lack of melanophages, and
      lack of hypergranulosis in some cases was seen in addition to classical features
      of LP. In 3 out of 4 patients with exclusive palmoplantar involvement diagnosis
      of LP was missed clinically. CONCLUSION: Involvement of palms and soles in LP
      poses a diagnostic challenge due to variable presentations. Histopathology is of
      vital importance for correct diagnosis and treatment.

PMID- 25071251
TI  - Serum Angiotensin converting enzyme in pemphigus vulgaris.
AB  - BACKGROUND: Pemphigus vulgaris is an autoimmune blistering skin disease with
      unknown etiology. Drugs such as angiotensin-converting enzyme (ACE) inhibitors
      may contribute in the pathogenesis of pemphigus. OBJECTIVE: We plan this essay to
      evaluate the serum ACE level in pemphigus vulgaris patients in comparison with
      healthy controls to recognize its possible role in disease pathogenesis or
      activity. METHODS: This study was planned and performed in the dermatology
      clinics of Shahid Beheshti University of MedicalSciences' Hospitals between July
      2010 and June 2011. Patients with new onset of pemphigus vulgaris were enrolled
      in our study. Control subjects were frequency-matched to cases by sex and age.
      Serum ACE was determined by the spectrophotometric method. RESULTS: Thirty-four
      patients with pemphigus vulgaris and 35 healthy individuals were recruited in the
      study. No statistical significant difference was detected in the mean level of
      serum ACE of the two groups (t-test, P = 0.11). The mean ACE level was
      significantly lower in male patients compared with male controls (P = 0.04).
      Moreover, a significant higher serum ACE level of patients with cutaneous
      involvement was observed compared to patients with mucosal involvement (P =
      0.02). CONCLUSIONS: Despite lack of any significant difference of serum ACE level
      between pemphigus and control group, the serum ACE level was considerably lower
      in male pemphigus vulgaris patients compared with male controls. Therefore, ACE
      might have some association with pemphigus vulgaris especially in male patients;
      however, further studies are required to confirm this association.

PMID- 25071252
TI  - Subungual squamous cell carcinoma: a case series.
AB  - Subungual tumors are rare in general. Of all tumors, subungual squamous cell
      carcinoma (SSCC) is the most frequent one. Protean clinical presentations and the
      lack of awareness of the disease are responsible for an incorrect or delayed
      diagnosis and subsequent delayed treatment. We have reported here four patients
      with SSCC who were previously wrongly diagnosed with a benign process and treated
      unsuccessfully for years. We would like to highlight the need of a biopsy in
      chronic or recurrent nail lesions that fail to respond to a previous conservative
      treatment in order to rule out SSCC. 

PMID- 25071253
TI  - Target-like Pigmentation After Minipunch Grafting in Stable Vitiligo.
AB  - Surgical treatment for vitiligo has been ever evolving. Each surgical modality
      has its own benefits and limitations. Miniature punch grafting is the most
      extensively performed surgery, which gives good results in stable vitiligo.
      Herein we report an unusual type of repigmentation observed after minipunch
      grafting in a patient of stable vitiligo, which resembled target-like lesions
      with a "perigraft halo" surrounding individual grafts. Such pigment spread
      occurred despite the use of 0.5 mm larger graft from the donor site. 

PMID- 25071254
TI  - Clinical Analysis of Thyroglobulin Antibody and Thyroid Peroxidase Antibody and
      their Association with Vitiligo.
AB  - BACKGROUND: Recently, the abnormal presence of thyroglobulin antibody (TG-Ab) and
      thyroid peroxidase antibody (TPO-Ab) has been reported in vitiligo patients, but
      presence of TG-Ab and TPO-Ab in patients of different ages and gender, and its
      association with vitiligo and thyroid autoimmunity has rarely been reported. The
      aim of our research was to determine whether vitiligo was associated with thyroid
      autoimmunity and figure out its relationship with age and gender. MATERIALS AND
      METHODS: We analyzed TG-Ab, TPO-Ab in age and gender matched 87 vitiligo patients
      and 90 healthy controls, the patients of vitiligo who were positive for the
      presence of TG-Ab and TPO-Ab were followed up to confirm autoimmune thyroid
      disease subsequently. RESULTS: Results showed that the frequencies of TG-Ab
      (23.0%, 20/87) positivity and TPO-AB (24.1%, 21/87) in vitiligo patients were
      significantly higher than that in healthy controls (P < 0.05). Moreover, The
      positivity for of TG-Ab and TPO-Ab was higher in 11-20-year age group and 21-40
      year age group than that in age matched healthy controls. We found female
      patients with vitiligo had higher positive frequencies of TG-Ab and TPO-Ab than
      healthy female controls. (34.1% vs. 8.8% and 34.1% vs. 11.1%, P = 0.000 and P =
      0.011). When 20 patients with TG-Ab and TPO-Ab positivity were followed up for
      three monthes, 14 of them (70%) were diagnosed as having autoimmune thyroid
      disease compared with age-matched healthy controls (16.7%, chi(2) = 5.4, P =
      0.02). CONCLUSION: TG-Ab and TPO-Ab are likely to be found in female teenagers
      with vitiligo, and are relevant with respect to subsequent development autoimmune
      thyroid disease.

PMID- 25071255
TI  - T-cell rich angiomatoid polypoid pseudolymphoma: a novel cutaneous
      pseudolymphoma.
AB  - Cutaneous pseudolymphomas refer to a group of benign reactive T or B cell
      lymphoproliferative processes that simulate cutaneous lymphomas. T cell rich
      angiomatoid polypoid pseudo lymphoma (TRAPP) of the skin is a unique form of T
      cell rich cutaneous pseudolymphoma. A 13-year-girl presented with an asymptomatic
      skin colored papule on the right elbow, the biopsy of which revealed features
      consistent with TRAPP. The dermis showed an infiltrate of lymphocytes, plasma
      cells, and histiocytes along with prominent vascular channels lined by plump
      endothelium. An immunohistochemical study showed a predominance of T cells over B
      cells. The morphological and immunohistochemical features pointed towards the
      diagnosis of TRAPP. We report this rare entity, only 17 cases of which have been
      described so far in literature. The differential diagnoses have also been
      discussed. 

PMID- 25071256
TI  - A Cross-sectional Study of Direct Immunofluorescence in the Diagnosis of
      Immunobullous Dermatoses.
AB  - BACKGROUND: Autoimmune blistering diseases are a group of bullous disorders
      characterized by pathogenic antibodies directed at the target antigens, which are
      components of the desmosomes or adhesion complex at the dermoepidermal junction.
      Direct immunofluorescence (DIF) is invaluable in the diagnosis of these lesions.
      AIM: The aim of this study was to evaluate the sensitivity of DIF in
      immunobullous dermatoses and to study the pattern of DIF. The study also aims to
      correlate DIF with clinical and histologic findings and to analyze discrepancies.
      MATERIALS AND METHODS: Total 100 biopsies received over a period of 2 years in
      the Department of Pathology were analyzed. DIF, histopathology and clinical data
      were reviewed. RESULTS: Out of 100, 89 cases showed DIF patterns concordant with
      clinical/histologic diagnosis. The sensitivity of DIF was 94.44% (51/58) in the
      pemphigus and 84% (21/25) in the bullous pemphigoid (BP) group, 100% each in
      dermatitis herpetiformis (2/2) and linear IgA disease (1/1). A total of 11
      histologically proven cases of immunobullous lesions were DIF negative-four
      (three of pemphigus vulgaris and one of BP) due to having no epidermis, three
      (cases of BP) owing to sampling/technical errors and the remaining four (cases of
      pemphigus vulgaris) due to being on treatment. CONCLUSION: Immunofluorescence
      helps confirm the diagnosis of bullous lesions in which there is clinical and the
      histopathologic overlap. Sampling errors contributed to false negative (FN)
      results.

PMID- 25071257
TI  - Delivery of Amphotericin B for Effective Treatment of Candida Albicans Induced
      Dermal Mycosis in Rats via Emulgel System: Formulation and Evaluation.
AB  - BACKGROUND: Amphotericin B (AmB) is among the gold standard antifungal agents
      used for the treatment of the wide range of fungal infections. However, the drug
      has various side- effects. Transdermal approach for the delivery of drug is one
      of the accepted and convenient modes of drug delivery. AIM: The current work was
      designed to formulate and to evaluate the AmB emulgel system. MATERIALS AND
      METHODS: In the preparation of AmB emulgel, Carbopol 930 was used as a gel in
      this study. The formulation was evaluated for viscosity, spreadability, drug
      content, drug release and in vitro and in vivo antifungal testing. RESULTS: AmB
      emulgel was found to penetrate skin effectively and without any irritation.
      Further, in vivo studies revealed effective therapeutic potential against Candida
      albicans induced dermal mycosis. CONCLUSIONS: The current work, for the first
      time, revealed effective delivery of AmB across the skin.

PMID- 25071259
TI  - Cutaneous Mycobacterium fortuitum Infection: Successfully Treated with Amikacin
      and Ofloxacin Combination.
AB  - Cutaneous infections caused by atypical mycobacteria are uncommon and the
      diagnosis can be missed unless there is strong clinical suspicion supported by
      laboratory confirmation. We report a case of chronic discharging sinus caused by
      Mycobacterium fortuitum in a young healthy immunocompetent individual. The
      patient recovered completely following amikacin and ofloxacin therapy. 

PMID- 25071258
TI  - Autologous serum therapy in chronic urticaria: a promising complement to
      antihistamines.
AB  - BACKGROUND: Chronic urticaria (CU) is a vexing problem and patients of CU suffer
      from the morbidity that arise from irritable itch and weals and are also
      subjected to a huge antihistamine pill burden. The symptoms are more in
      autoreactive urticaria (AU) where auto-antibodies in blood flares-up the
      condition. Search for newer effective modalities which can reduce pill burden is
      a felt need. AIMS: This study evaluates the effectiveness of autologous serum
      therapy (AST) in CU and also determines its usefulness in AU. MATERIALS AND
      METHODS: Double blind, parallel group, randomized, controlled study. Fifty four
      patients were given AST and 57 patients were given injection normal saline
      (placebo), along with cetirizine in an on-demand basis in both groups.
      AST/Placebo was given weekly for nine weeks and followed-up for a total period of
      24 weeks. AU was diagnosed by autologous serum skin test. Urticaria total
      severity score (TSS), Urticaria activity score (UAS), Dermatologic life quality
      index (DLQI) was used as primary effectiveness variables. Safety parameters
      assessed were the spontaneously reported adverse events and laboratory
      parameters. RESULTS: TSS showed significant improvement from baseline, 7(th) week
      and 8(th) week onwards in AST group and placebo group respectively. Group
      comparison showed significant improvement 4(th) week onwards. UAS showed similar
      results. DLQI showed significant improvement in AST group compared to placebo at
      the end of study. Both AU and non-AU patients showed comparable improvement of
      TSS. CONCLUSION: AST shows promise in treatment of urticaria regardless of the
      autoreactive nature.

PMID- 25071260
TI  - Efficacy and tolerability of topical fixed combination of nadifloxacin 1% and
      adapalene 0.1% in the treatment of mild to moderate acne vulgaris in Indian
      patients: a multicenter, open-labelled, prospective study.
AB  - BACKGROUND: A combination of topical retinoid and antibacterial therapy is often
      advocated for acne to enhance therapeutic efficacy. AIMS: A preliminary study to
      evaluate the efficacy and tolerability of a topical fixed combination of
      nadifloxacin (1%) and adapalene (0.1%) in the treatment of mild to moderate acne
      in Indian patients. MATERIALS AND METHODS: This was an open-labeled, phase 3 non
      randomized, non-comparative study conducted at five centers (Ahmedabad, Nagpur,
      Thane, Bangalore, and Mumbai) across India. Of 119 enrolled patients with mild to
      moderate acne, 117 patients were evaluated at the end of the study for efficacy
      parameters. A fixed combination of nadifloxacin (1%) and adapalene (0.1%) topical
      gel was applied at the affected area once at night for a period of 8 weeks.
      Reduction in the total, inflammatory and non-inflammatory lesion counts from the
      baseline, investigator global assessment (IGA) and reduction in the severity of
      acne as per combined acne severity classification were the primary efficacy
      variables measured at 2 weeks, 4 weeks, and 8 weeks. RESULTS: Overall, 98.3%
      patients showed a statistically significant progressive reduction in non
      inflammatory lesion counts, inflammatory lesion counts, and total lesion counts
      over the study duration. By the end of 8 weeks, 75% of the patients had their
      global assessment scores approaching to normal healthy skin score. The adverse
      events were mild to moderate in severity. CONCLUSION: This preliminary study
      shows that a fixed combination of 1% nadifloxacin and 0.1% adapalene topical gel
      could be an effective and well-tolerated option for the treatment of mild to
      moderate acne vulgaris. However, further well-controlled, randomized and
      comparative evaluation of this combination is necessary.

PMID- 25071261
TI  - Association of bullous pemphigoid with malignancy: a myth or reality?
AB  - Bullous pemphigoid (BP) is an autoimmune sub-epidermal blistering disorder of the
      skin. The association of BP with internal malignancy has always been a matter of
      debate with no consensus reached despite many published case reports and clinical
      trials. However, we report a hitherto unreported association of BP with squamous
      cell carcinoma of the tongue, wherein the patient had a recalcitrant downhill
      course despite adequate treatment measures with control of skin lesions being
      achieved only following excision of the tumor, and relapse coinciding with
      detection of metastasis. Hence, given the clinical behavior, it is reasonable to
      speculate that the association of malignancy was more than co-incidental. 

PMID- 25071262
TI  - An Indian boy with griscelli syndrome type 2: case report and review of
      literature.
AB  - Griscelli syndrome 2 is a rare autosomal recessive disorder of pigmentary
      dilution of hair, skin, splenohepatomegaly, pancytopenia, immune and neurologic
      dysfunction. Clinical course is characterized by recurrent infection triggered by
      uncontrolled T-lymphocyte and macrophage activation, called hemophagocytic
      syndrome. Since the primary presentation is with depigmented hair, we attempt to
      highlight diagnostic difficulties in such cases in developing countries like ours
      where pigmentary changes in hair and skin are commonly attributed to severe
      malnutrition. We also evaluated phenotype of all 10 cases of genotype (c.C550T;
      p.R184X), collected from published literature worldwide and emphasize the
      potential role of above mutation as hotspot in Southeast Asian region. 

PMID- 25071263
TI  - Follicular Porokeratosis at alae Nasi; A Case Report and Short Review of
      Literature.
AB  - Porokeratosis are disorders of keratinization, characterized histologically by a
      parakeratotic column, the cornoid lamellae, and clinically by a distinct
      peripheral ridge. Porokeratosis usually occurs on the trunk or extremities, and
      facial lesions are rare. Follicular involvement, identified by follicular
      localization of cornoid lamellae, is uncommon and described only in association
      with disseminated superficial actinic porokeratosis (DSAP) and porokeratosis
      Mibelli (PM). A 34-Year- old woman is presented with asymptomatic 1 cm plaque
      lesion with hyperkeratotic ridge and depressed center on her nose since three
      years. Histopathological examination of a biopsy revealed cornoid lamellae
      confined exclusively to the follicle. 

PMID- 25071264
TI  - Toxic Epidermal Necrolysis-like Rash of Lupus: A Dermatologist's Dilemma.
AB  - For most dermatologists, the challenge posed by toxic epidermal necrolysis (TEN)
      lies not in its diagnosis, but in pulling the patient out of this life
      threatening condition. However, when a patient presents with a TEN-like picture
      in the background of lupus erythematosus (LE), it becomes difficult to decide
      whether the eruption is drug induced or a manifestation of lupus itself. 

PMID- 25071265
TI  - Eccrine angiomatous hamartoma: late onset facial presentation.
AB  - Eccrine angiomatous hamartoma (EAH) is a very rare benign neoplastic condition
      characterized by hamartomatous proliferation of eccrine glands and accompanying
      blood vessels and lymphatics. These lesions are more often present at birth or
      appear during early infancy and childhood and present as solitary nodule or
      plaque with occasional pain and sweating. They are generally present on the
      extremities, mostly the palms and soles. We report here a case of EAH in a 20
      year-old female who presented with a solitary angiomatous plaque close to the
      lower eyelid of the right eye with occasional pain and sweating for its rarity. 

PMID- 25071266
TI  - Stewart-bluefarb acroangiodermatitis in a case of parkes-weber syndrome.
AB  - Stewart-Bluefarb acroangiodermatitis is the occurrence of pseudo-kaposiform
      changes with an underlying arterio-venous malformation. Parkes-Weber syndrome is
      a triad of arterio-venous malformation with varicose veins with bony and soft
      tissue hypertrophy involving the extremity. A 13 year-old-female presented with
      ulcerated growth with bleeding episodes on right leg since past four years. A
      reddish discoloration over right leg was noticed at four years of age which
      remained unchanged until nine years of age, after which it showed rapid increase
      in size along with disproportionate increase in length and girth of right lower
      limb. Examination revealed hyperpigmented soft verrucous plaque over the right
      lower one-third of leg, along with presence of ulcers and dilated tortuous veins
      in the right lower leg with thrill and bruit over the right popliteal and
      inguinal region. A differential diagnosis of verrucous hemangioma and arterio
      venous malformation with pseudo-kaposiform change was considered. Skin biopsy
      showed multiple fenestrated capillaries with perivascular lymphocyte infiltrate
      suggestive of capillary malformations. X-ray showed osteolytic defect in right
      tibia. Duplex ultrasound and magnetic resonance imaging of right leg showed
      multiple fast flowing small and medium sized arterio-venous malformations of
      small to moderate size. Thus, on the basis of clinical and radiological features,
      we made a diagnosis of Stewart-Bluefarb type of acroangiodermatitis with Parkes
      Weber syndrome. She was managed conservatively with compression stockings. 

PMID- 25071267
TI  - Comments on tuberculosis verrucosa cutis presenting as diffuse plantar
      keratoderma: an unusual sight.

PMID- 25071268
TI  - Congenital smooth muscle hamartoma at unusual location.

PMID- 25071269
TI  - Intralesional steroid injections: look before you leap!

PMID- 25071270
TI  - Fixed drug eruption to levocetirizine and cetirizine.

PMID- 25071271
TI  - Coexistent actinomycosis and eumycetoma in an immunocompetent patient.

PMID- 25071272
TI  - Pseudo-Kaposi's Sarcoma of the Hand Associated with Acquired Iatrogenic
      Arteriovenous Fistula.

PMID- 25071273
TI  - Biosimilars in pemphigus vulgaris.

PMID- 25071274
TI  - Persistent eczematous lesions over the body.

PMID- 25071276
TI  - S-100 immunostaining in the Distinction of Borderline Tuberculoid Leprosy from
      other Cutaneous Granulomas.
AB  - BACKGROUND: Histopathologic diagnosis of borderline tuberculoid leprosy (BTL) is
      fraught with hurdles. It overlaps with other granulomas and documenting nerve
      involvement is the key to correct diagnosis. This is difficult on H and E
      sections alone. S-100 immunostaining may help in this regard. OBJECTIVES: To
      study the patterns of nerve involvement in BTL and other cutaneous granulomas
      using S-100 immunostain and compare its sensitivity with that of H and E
      staining, in both adequate and inadequate biopsies. MATERIALS AND METHODS: A
      total of 20 cases of BTL were reviewed. And, 19 biopsies from other cutaneous
      granulomas were taken as controls. S-100 immunostaining was done on paraffin
      sections. The pattern of nerve involvement was graded as intact, infiltrated
      and/or fragmented, intact with perineural inflammation. RESULTS: Of the 20 cases
      of BTL, S-100 demonstrated infiltrated and/or fragmented nerves in 15 and absent
      nerves in 5 cases. H and E stain identified neuritis in eight cases. The
      sensitivity of S-100 and H and E is 0.78 and 0.41. In the 19 controls, S-100
      identified normal nerves in 16 with 7 showing perineural inflammation only and
      their absence in 2 cases. H and E identified normal nerves in nine cases. The
      sensitivity of S-100 and H and E is 0.83 and 0.41. In biopsies where subcutis was
      absent, the sensitivity of S-100 in identifying nerve involvement is 0.66
      compared with H and E 0.33. CONCLUSION: S-100 staining is an efficient ancillary
      aid in distinguishing BTL from other granulomas and is superior to H and E in
      identifying nerve involvement, even where subcutis is absent. Infiltration and/or
      fragmentation of nerves by S-100 is the only reliable marker of BTL.

PMID- 25071275
TI  - The relationship between alopecia areata and alexithymia, anxiety and depression:
      a case-control study.
AB  - BACKGROUND: Alopecia areata (AA) is a skin disease characterized by the sudden
      appearance of areas of hair loss on the scalp and other hair-bearing areas, but
      its aesthetic repercussions can lead to profound changes in patient's
      psychological status and relationships. AIM: The goal was to investigate a
      possible relationship between AA and alexithymia as well as two other emotional
      dimensions, anxiety and depression. MATERIALS AND METHODS: Fifty patients with AA
      seen in the Department of Dermatology of Hedi Chaker University Hospital, Sfax
      were included in this study. Anxiety and depression were evaluated by Hospital
      Anxiety and Depression scale questionnaire, alexithymia was assessed by Toronto
      Alexithymia scale 20, and severity of AA was measured by Severity of Alopecia
      Tool. RESULTS: Patient's mean age was 32.92 years. 52% of patients were females.
      Depression and anxiety were detected respectively in 38% and 62% of patients.
      There was statistically significant difference between patients and control group
      in terms of depression (P = 0.047) and anxiety (P = 0.005). Forty-two percent of
      patients scored positive for alexithymia. No significant difference was found
      between patient and control groups (P = 0.683) in terms of alexithymia. Anxiety
      was responsible for 14.7% of variation in alexithymia (P = 0.047). CONCLUSIONS:
      Our study shows a high prevalence of anxiety and depressive symptoms in AA
      patients. Dermatologists should be aware of the psychological impact of AA,
      especially as current treatments have limited effectiveness.

PMID- 25071277
TI  - Two cases of multiple subcutaneous cystic phaeohyphomycosis in immunocompromised
      patients with a rare causative organism.
AB  - Phaeohyphomycosis comprises a spectrum of mycotic infectious diseases caused by
      heterogeneous group of phaeoid fungi. A subcutaneous cystic swelling with
      histological hallmark of pigmented hyphae in tissues accompanied by pyogenic
      granuloma is diagnostic of phaeohyphomycosis. We present two cases of
      phaeohyphomycosis in 65- and 55-year-old male agriculturalists, who presented
      with multiple, cystic soft-tissue masses involving extremities. Culture was done
      in one case and the specific organism was identified as Aureobasidium pullulans. 

PMID- 25071278
TI  - Castleman's Disease with Paraneoplastic Pemphigus.
AB  - Castleman's disease is a rare autoimmune disorder with varied clinical
      presentations. Castleman's commonly involves mediastinum and hence it is thoracic
      in most of the reported cases. Paraneoplastic pemphigus (PNP) and myasthenia
      gravis can be associated with multicentric Castleman's disease. Its association
      with HIV, Kaposi sarcoma, and lymphoma is also well known. We report a rare
      combination of unicentric, extrathoracic Castleman's disease with PNP and
      myasthenia gravis. 

PMID- 25071279
TI  - Becker's Nevus Syndrome.
AB  - Becker's nevus is a cutaneous hamartoma characterized by circumscribed
      hyperpigmentation with hypertrichosis. Becker's nevus syndrome is an association
      of Becker's nevus with unilateral breast hypoplasia and muscle, skin, and/or
      skeletal abnormalities. We here report a case of a 15 year-old female who
      presented with bilateral Becker's nevus over her groins, thighs, vulva, and in
      front of the neck from the age of 5 years. She had associated mental retardation,
      delayed development of mile stones, delayed puberty, dwarfism, depressed nasal
      bridge, long slender digits, crowding of lateral toes, valgus deformity of first
      metatarsophalangeal joint, mitral valve prolapse, muddy conjunctiva with
      hypertrophic and hyperpigmented caruncle of both eyes, ichthyosis, brownish hair,
      and absence of axillary and pubic hair. On histopathological examination collagen
      hamartoma underneath the Becker's nevus was found. 

PMID- 25071280
TI  - A case of extensive multifocal tuberculosis verrucosa cutis.
AB  - Tuberculosis is probably as old as the human race itself. Cutaneous tuberculosis
      constitutes a very small proportion of extra pulmonary tuberculosis. Extensive,
      multifocal involvement of cutaneous tuberculosis is a very rare manifestation. We
      report one such case of extensive, multifocal tuberculosis verrucosa cutis in a
      30-year-old immunocompetent male patient in the absence of any primary tubercular
      focus. 

PMID- 25071281
TI  - Inflammatory nevus comedonicus with epidermoid cyst.
AB  - We present here a case of inflammatory nevus comedonicus (NC) in a young male
      distributed along the Blaschko's lines only over the right lower limb and
      associated with epidermoid cysts. The case was unique in terms of isolated
      involvement of lower limb and the rare association of epidermoid cyst. 

PMID- 25071282
TI  - Tumor attributes predicting cutaneous metastatic destiny: a report of two
      interesting cases.
AB  - Cutaneous metastases are the result of complex interaction between the tumor
      cells ("seed") and the host environment ("soil"). Metastases to the skin can be
      an early sign of internal malignancy or represent recurrence of the primary tumor
      and portends a poorer prognosis. Invasion and metastasis are the hallmarks of on
      cogenesis. Skin is the largest organ in the body, but the incidence of metastases
      is low. With advances in molecular biology, factors responsible for the
      initiation and perpetuation of metastatic tumor cells at distant sites are being
      elucidated. The concept of "pre-metastatic niche" and interaction between various
      chemokines has given a new outlook in understanding the organ specificity of
      metastatic tumor cells. We present two cases of cutaneous metastases with
      interesting clinical findings correlating with its biologic subtypes. 

PMID- 25071283
TI  - Localized cutaneous mucinosis associated with multiple myeloma: a rare
      presentation.
AB  - Lichen myxoedematosus (LM), a form of primary cutaneous mucinosis, may present
      either as localized less severe form called papular mucinosis or diffuse more
      severe form called scleromyxoedema. The diffuse form is almost always associated
      with monoclonal gammopathy, whereas localized form is not. We report an atypical
      case of localized form of LM associated with multiple myeloma in a 66-year-old
      male, who presented with asymptomatic waxy papular eruption on extremities, which
      on histopathological examination confirmed the diagnosis of cutaneous mucinosis.
      After initially being put on steroids and hydroxychloroquine with minimal
      improvement, patient subsequently presented with encephalopathy and on evaluation
      revealed hypernatremia, hypercalcemia, hypergammaglobulinemia, reversal of
      albumin-globulin (A/G) ratio, azotemia, and lytic lesions in skull X-ray. Bone
      marrow aspiration and biopsy confirmed multiple myeloma. Patient was successfully
      treated with standard treatment regimen for multiple myeloma with bortezumib and
      dexamethasone and his skin lesions subsided completely. 

PMID- 25071284
TI  - Primary cutaneous coccidioidomycosis: first imported case in north India.
AB  - Coccidioidomycosis is a fungal disease found only in the Western Hemisphere. In
      recent years, the incidence of the disease has increased in California and
      Arizona, which may be partially due to the rapid immigration of previously
      unexposed persons from states outside the endemic areas. The disease in the
      nonendemic areas is usually imported. Determining a history of exposure is
      critical for performing the diagnosis of coccidioidomycosis in these cases.
      Histopathological examination is the key to the diagnosis when fungal culture and
      molecular studies are not available. We hereby report an imported case of
      cutaneous coccidioidomycosis, which to the best of our knowledge is the first
      case report from North India. 

PMID- 25071285
TI  - Autosomal recessive anhidrotic ectodermal dysplasia: a rare entity.
AB  - We describe a case of anhidrotic ectodermal dysplasia (AED) with an autosomal
      recessive mode of inheritance, a very rare entity, in a 2-year-old female child
      of two asymptomatic, consanguineous parents. Their previous child also had a
      similar condition. Autosomal recessive AED (AR-AED) can have its full expression
      both in males and females and it is clinically indistinguishable from the x
      linked recessive AED (XL-AED), which is the most common type of ectodermal
      dysplasia. Unlike the partially symptomatic carriers of XL-AED, the heterozygotes
      of AR-AED are phenotypically asymptomatic. 

PMID- 25071286
TI  - Angiolymphoid hyperplasia with eosinophilia mimicking multiple cylindromas: a
      rare case report.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare and idiopathic
      vascular disorder. It is characterized by red to brown papules and nodules,
      typically localized on the head and neck, particularly around the ear as singular
      or multiple lesions. Although ALHE is a benign disease, lesions are often
      persistent and difficult to eradicate. Young to middle age women are more
      commonly affected. The histological examination corresponds to a florid vascular
      proliferation with atypical endothelial cells surrounded by a lymphocytic and
      eosinophilic infiltrate. We describe an elderly male with multiple nodular
      lesions over the scalp mimicking cylindromas; the histological examination was
      consistent with ALHE. 

PMID- 25071287
TI  - Primary tuberculosis in soft palate: case report of a rare entity.
AB  - A 40-year-old male patient presented to our clinic with history of dysphagia and
      ulceration in the palate for two months. After history-taking and thorough
      clinical examination, investigations like routine blood parameters, chest
      skiagram, sputum for acid-fast bacilli, ultrasonography of the abdomen, and
      biopsy from the palatal lesion were performed. No evidence in support of
      pulmonary or abdominal tuberculosis was found. Histopathological examination of
      the biopsy revealed granulomatous inflammation with Langhans giant cells and
      caseation necrosis. Diagnosis of primary tuberculosis of soft palate was made.
      Anti- tubercular regimen (CAT I) for 6 months was prescribed, and we got a
      dramatic response noted within 15 days. As isolated tuberculosis of soft palate
      is a very rare entity, one should, therefore, consider it in any case of chronic
      ulcer of the soft palate. Response to CAT 1 was excellent in our case. 

PMID- 25071288
TI  - Bullous hemorrhagic dermatosis: a case report.
AB  - We present a case of hemorrhagic bullous dermatosis occurring in areas distant
      from the site of injection of enoxaparin. A 88 year old woman was admitted for
      inter trochantric fracture. She was put enoxaparin 60mg subcutaneous 12 hrly for
      deep vein thrombosis. After 5 days she developed huge hemorrhagic bulla on left
      leg and multiple hemorrhagic bullae at other sites distant from injected site. A
      diagnosis of Bullous hemorrhagic dermatoses due to enoxaparin was made.
      Enoxaparin was stopped and started on oral heparin. Lesions started to regress.
      Only 9 similar cases have been reported throughout world and none from India. 

PMID- 25071289
TI  - Levetiracetam induced urticarial vasculitis: a preliminary report.

PMID- 25071290
TI  - Herpes zoster affecting all three divisions of trigeminal nerve in an
      immunocompetent male: a rare presentation.

PMID- 25071291
TI  - Iatrogenic patterned scar secondary to branding.

PMID- 25071292
TI  - Eruptive angiokeratomas on the glans penis.

PMID- 25071293
TI  - Paraphenylenediamine-induced Cutaneous Pseudolymphoma.

PMID- 25071294
TI  - Uniform and non-uniform modes of nanosecond-pulsed dielectric barrier discharge
      in atmospheric air: fast imaging and spectroscopic measurements of electric
      field.
AB  - In this study, we report experimental results on fast ICCD imaging of development
      of nanosecond-pulsed dielectric barrier discharge (DBD) in atmospheric air and
      spectroscopic measurements of electric field in the discharge. Uniformity of the
      discharge images obtained with nanosecond exposure times were analyzed using chi
      square test. The results indicate that DBD uniformity strongly depends on applied
      (global) electric field in the discharge gap, and is a threshold phenomenon. We
      show that in the case of strong overvoltage on the discharge gap (provided by
      fast rise times), there is transition from filamentary to uniform DBD mode which
      correlates to the corresponding decrease of maximum local electric field in the
      discharge.

PMID- 25071295
TI  - Bootstrapping on undirected binary networks via statistical mechanics.
AB  - We propose a new method inspired from statistical mechanics for extracting
      geometric information from undirected binary networks and generating random
      networks that conform to this geometry. In this method an undirected binary
      network is perceived as a thermodynamic system with a collection of permuted
      adjacency matrices as its states. The task of extracting information from the
      network is then reformulated as a discrete combinatorial optimization problem of
      searching for its ground state. To solve this problem, we apply multiple
      ensembles of temperature regulated Markov chains to establish an ultrametric
      geometry on the network. This geometry is equipped with a tree hierarchy that
      captures the multiscale community structure of the network. We translate this
      geometry into a Parisi adjacency matrix, which has a relative low energy level
      and is in the vicinity of the ground state. The Parisi adjacency matrix is then
      further optimized by making block permutations subject to the ultrametric
      geometry. The optimal matrix corresponds to the macrostate of the original
      network. An ensemble of random networks is then generated such that each of these
      networks conforms to this macrostate; the corresponding algorithm also provides
      an estimate of the size of this ensemble. By repeating this procedure at
      different scales of the ultrametric geometry of the network, it is possible to
      compute its evolution entropy, i.e. to estimate the evolution of its complexity
      as we move from a coarse to a ne description of its geometric structure. We
      demonstrate the performance of this method on simulated as well as real data
      networks.

PMID- 25071296
TI  - Direct synthesis of arenecarboxamides through Friedel-Crafts acylation using
      ureas.
AB  - The reaction of urea derivatives that contain the phenothiazine unit with
      trifluoromethanesulfonic anhydride in the presence of electron-rich aromatic
      compounds leads to the formation of arenecarboxamides. The reaction has been
      successfully demonstrated for several inter- and intramolecular systems.

PMID- 25071297
TI  - Identifying Baseline Covariates for Use in Propensity Scores: A Novel Approach
      Illustrated for a Non-randomized Study of Recovery High Schools.
AB  - There are many situations where random assignment of participants to treatment
      and comparison conditions may be unethical or impractical. This article provides
      an overview of propensity score techniques that can be used for estimating
      treatment effects in non-randomized quasi-experimental studies. After reviewing
      the logic of propensity score methods, we call attention to the importance of the
      strong ignorability assumption and its implications. We then discuss the
      importance of identifying and measuring a sufficient set of baseline covariates
      upon which to base the propensity scores and illustrate approaches to that task
      in the design of a study of recovery high schools for adolescents treated for
      substance abuse. One novel approach for identifying important covariates that we
      suggest and demonstrate is to draw on the predictor-outcome correlations compiled
      in meta-analyses of prospective longitudinal correlations.

PMID- 25071298
TI  - Bayes variable selection in semiparametric linear models.
AB  - There is a rich literature on Bayesian variable selection for parametric models.
      Our focus is on generalizing methods and asymptotic theory established for
      mixtures of g-priors to semiparametric linear regression models having unknown
      residual densities. Using a Dirichlet process location mixture for the residual
      density, we propose a semiparametric g-prior which incorporates an unknown matrix
      of cluster allocation indicators. For this class of priors, posterior computation
      can proceed via a straightforward stochastic search variable selection algorithm.
      In addition, Bayes factor and variable selection consistency is shown to result
      under a class of proper priors on g even when the number of candidate predictors
      p is allowed to increase much faster than sample size n, while making sparsity
      assumptions on the true model size.

PMID- 25071299
TI  - A Modified Adaptive Lasso for Identifying Interactions in the Cox Model with the
      Heredity Constraint.
AB  - In many biomedical studies, identifying effects of covariate interactions on
      survival is a major goal. Important examples are treatment-subgroup interactions
      in clinical trials, and gene-gene or gene-environment interactions in genomic
      studies. A common problem when implementing a variable selection algorithm in
      such settings is the requirement that the model must satisfy the strong heredity
      constraint, wherein an interaction may be included in the model only if the
      interaction's component variables are included as main effects. We propose a
      modified Lasso method for the Cox regression model that adaptively selects
      important single covariates and pairwise interactions while enforcing the strong
      heredity constraint. The proposed method is based on a modified log partial
      likelihood including two adaptively weighted penalties, one for main effects and
      one for interactions. A two-dimensional tuning parameter for the penalties is
      determined by generalized cross-validation. Asymptotic properties are
      established, including consistency and rate of convergence, and it is shown that
      the proposed selection procedure has oracle properties, given proper choice of
      regularization parameters. Simulations illustrate that the proposed method
      performs reliably across a range of different scenarios.

PMID- 25071300
TI  - Precise measurement of chromium isotopes by MC-ICPMS.
AB  - We report novel analytical procedures allowing for the concurrent determination
      of the stable and mass-independent Cr isotopic composition of silicate materials
      by multiple collector inductively coupled mass spectrometry (MC-ICPMS). In
      particular, we focus on improved precision of the measurement of the neutron-rich
      isotope 54Cr. Because nitride and oxide interferences are a major obstacle to
      precise and accurate 54Cr measurements by MC-ICPMS, our approach is designed to
      minimize these interferences. Based on repeat measurements of standards, we show
      that the mass-independent 53Cr and 54Cr compositions can be routinely determined
      with an external reproducibility better than 2.5 and 5.8 ppm (2 sd),
      respectively. This represents at least a two-fold improvement compared to
      previous studies. Although this approach uses significantly more Cr (30-60 MUg)
      than analysis by thermal ionization mass spectrometry (TIMS), our result indicate
      that it is possible to obtain an external reproducibility of 19 ppm for the
      MU54Cr when consuming amounts similar to that typically analyzed by TIMS (1 MUg).
      In addition, the amount of time required for analysis by MC-ICPMS is much shorter
      thereby enabling a higher sample throughput. As a result of the improved
      analytical precision, we identified small apparent mass-independent differences
      between different synthetic Cr standards and bulk silicate Earth (BSE) when using
      the kinetic law for the mass bias correction. These differences are attributed to
      the Cr loss by equilibrium processes during production of the synthetic
      standards. The stable isotope data concurrently obtained have a precision of
      0.050/00 Da -1, which is comparable to earlier studies. Comparison of the
      measured isotopic composition of four meteorites with published data indicates
      that Cr isotope data measured by the technique described here are accurate to
      stated uncertainties. The stable Cr composition of the Bilanga and NWA 2999
      achondrites suggests that the differences in the stable Cr isotope composition of
      Earth and chondrites may reflect heterogeneity of their precursor material rather
      than Cr isotope fractionation during metal-silicate segregation of Earth. Lastly,
      a step wise dissolution experiment of the CI chondrite Ivuna reveals previously
      unknown carriers of large mass-dependent Cr stable isotope variations that co
      vary with the known presence of carriers of large nucleosynthetic anomalies,
      demonstrating one advantage of this technique.

PMID- 25071301
TI  - Parental Emotion Coaching: Associations With Self-Regulation in
      Aggressive/Rejected and Low Aggressive/Popular Children.
AB  - This study investigated associations between maternal and paternal emotion
      coaching and the self-regulation skills of kindergarten and first-grade children.
      Participants were 54 children categorized as either aggressive/rejected or low
      aggressive/popular by peer reports. Findings indicated a statistical trend for
      fathers of low aggressive/popular children to engage in more emotion coaching
      than fathers of aggressive/rejected children. Paternal emotion coaching accounted
      for significant variance in children's regulation of attention. Maternal emotion
      coaching moderated the relation between children's status and regulation of
      emotion. Findings suggest that interventions focused on parental emotion coaching
      may prove beneficial for increasing the self-regulation and attention skills of
      children with social and conduct problems.

PMID- 25071302
TI  - Effects of a Psychosocial Intervention on Caregivers of Recently Placed Nursing
      Home Residents: A Randomized Controlled Trial.
AB  - Many caregivers continue to provide care and support to their care recipients
      after institutional placement. A two-group randomized controlled trial was
      carried out to test the efficacy of a psychosocial intervention for informal
      caregivers whose care recipients resided in a long-term care facility. The
      intervention was delivered during the 6 month period following baseline
      assessment. Follow-up assessments were carried out at 6, 12, and 18 months.
      Primary outcomes were caregiver depression, anxiety, burden, and complicated
      grief. Significant time effects were found for all three primary outcomes showing
      that caregiver depression, anxiety, and burden improved over time. No treatment
      effects were found for these outcomes. However, complicated grief was
      significantly lower for caregivers in the treatment condition.

PMID- 25071303
TI  - Comparison of percutaneous ablation technologies in the treatment of malignant
      liver tumors.
AB  - Tumor ablation is a minimally invasive technique used to deliver chemical,
      thermal, electrical, or ultrasonic damage to a specific focal tumor in an attempt
      to achieve substantial tumor destruction or complete eradication. As the
      technology continues to advance, several image-guided tumor ablations have
      emerged to effectively manage primary and secondary malignancies in the liver.
      Percutaneous chemical ablation is one of the oldest and most established
      techniques for treating small hepatocellular carcinomas. However, this technique
      has been largely replaced by newer modalities including radiofrequency ablation,
      microwave ablation, laser-induced interstitial thermotherapy, cryoablation, high
      intensity-focused ultrasound ablation, and irreversible electroporation. Because
      there exist significant differences in underlying technological bases,
      understanding each mechanism of action is essential for achieving desirable
      outcomes. In this article, the authors review the current state of each ablation
      method including technological and clinical considerations. 

PMID- 25071305
TI  - Racial/Ethnic Composition and Violence: Size-of-Place Variations in Percent Black
      and Percent Latino Effects on Violence Rates.
AB  - According to racial invariance positions and mainstream sociological perspectives
      on race and crime, race differences in structural conditions should account for
      most if not all of the racial composition (or percent black) effect on aggregate
      level violence rates. However, prior research (mostly conducted prior to 1990)
      generally provides mixed or contrary evidence for this position, showing instead
      that greater concentrations of blacks are linked to increased violence even after
      accounting for racial differences in socioeconomic conditions. The current study
      uses recent data and a novel unit of analysis to go beyond extant research in two
      ways. First, we include percent Latino in our examination of the extent to which
      both racial and ethnic composition effects on violent crime rates are mediated by
      racial/ethnic disparities in socioeconomic disadvantage. Second, we test whether
      racial/ethnic composition effects are conditioned by size of place, through the
      use census places as a uniquely varying unit of analysis. We find that both black
      and Latino composition effects are partly explained by controlling for structural
      conditions (especially structural disadvantage), but this characterizes smaller
      places much more than the largest, most urbanized places.

PMID- 25071304
TI  - Image-guided percutaneous ablation of hepatic malignancies.
AB  - The liver is a common site of primary and secondary malignancies, often resulting
      in significant morbidity and mortality. Evaluating these patients in a
      multidisciplinary setting allows for optimal utilization of all oncologic
      therapies including surgery, radiation, systemic chemotherapy, transarterial
      therapies, and ablation. While surgical intervention often provides the best
      outcomes when treating most hepatic tumors, many patients are not surgical
      candidates due to extensive tumor burden, underlying liver disease, or other
      comorbid conditions. The evolution of imaging and ablation devices has allowed
      for the increased utilization of percutaneous ablation as definitive and
      palliative treatment of primary and metastatic hepatic malignancies. Ablation
      induces tumor necrosis by injection of chemicals (chemical ablation) or
      temperature modification (thermal ablation). The goal of this review is to
      provide an overview of different ablation techniques commonly used for hepatic
      malignancies, discuss the oncologic outcomes of these interventions, and outline
      the current indications, contraindications, and reported complications of these
      therapies. 

PMID- 25071306
TI  - Laser Therapy is not the only thing on the move!

PMID- 25071307
TI  - History of the World Federation of Societies for Laser Medicine and Surgery
      (WFSLMS) and its Non-Profit Organization (NPO-WFSLMS): Part 1: Origins to
      Inaugural Meeting, 2005.
AB  - BACKGROUND AND AIMS: The first society formed to represent the "new" field of
      laser applications in medicine and surgery was the late Professor Kaplan's
      International Society for Laser Surgery and Medicine, held in Israel in 1975.
      Following the ISLSM lead, a large number of national and international societies
      were very swiftly formed. As the number grew, it became obvious that some sort of
      linking forum would help all these separate societies to pool the knowledge of
      their members for the good of the clinicians and their patients. The World
      Federation of Societies for Laser Medicine and Surgery was formed to attempt to
      fill this role. The History: At the 1996 meeting of the Greek Medical Laser
      Association, the first international forum of representatives from 17
      international and national laser societies was convened by Professor Nick
      Nicolopoulos, and the seed of an idea for a centralized forum to help separate
      laser societies coordinate efforts and knowledge was planted. This seed was
      nurtured by the ISLSM as the first medical laser society, and forums were called
      together at each meeting of the ISLSM and the other related societies from 1997
      to 2003. At the 2004 Chinese Medical Laser Society meeting, the idea of worldwide
      federation of laser societies crystallized into a more tangible form The
      Inaugural WFSLMS Congress: The convening of the first WFSLMS congress took place
      in Tokyo in 2005, under the leadership of Professor Kazuhiko Atsumi. At this
      meeting, Professor Kaplan proposed that a Medical Laser Foundation should be
      established and donated the first seed money for its formation. Because of the
      Japanese legal requirements, a foundation was impossible and so a Non-profit
      Organization (NPO-WFSLMS) was started, based in Japan, to oversee the work and
      fund the tasks of promoting laser surgery and medicine worldwide, for the good of
      mankind: the financing, running and holding WFSLMS congresses became one of the
      tasks of NPO-WFSLMS. CONCLUSION: Both the WFSLMS and NPO-WFSLMS were therefore on
      their way to working together for a cohesive approach to try and coordinate the
      work of all societies dedicated to laser medicine and surgery under the WFSLMS
      umbrella, with NPO-WFSLMS continuously gathering, administering and disbursing
      the funds to allow the WFSLMS to run its 4-yearly meetings.

PMID- 25071308
TI  - Adjusting the light in the limit conditions of consciousness by the means of
      ascending reticular activating system (ARAS) and of subordinated systems: Part 2:
      Continuation & Conclusion of the Article.
AB  - BACKGROUND: In our activity in the Ambulance Service of Bucharest Municipality
      during March 2002 - March 2003 we studied a casuistry of patients who had fallen
      in a coma of varying degrees. To aid better understanding of coma, the concept of
      "pre-coma stage" or "diencephalic 0 stage" was introduced. This concept
      complements the Arseni classification already used in medical practice, because
      some doctors alternatively use the term of "inaugural coma" for the same
      condition that we call diencephalic "0 stage". In the median hypothalamus and on
      the retino-hypothalamic path (SCN - AN) optical waves are transmitted, probably
      in the near infrared spectral range (800-1000 nm) in what we term the ascending
      reticular activating system (ARAS). These waves would constitute a means of
      transmitting information via the ARAS about the infradian biorhythm of
      coordination (frequencies below 1 cycle/28 hours), essential for the modulation
      and pre-processing of the consciousness and wakefulness, a fact which has already
      been demonstrated in animals. METHODS: The current work is based on observations
      made on a group of 51 patients with the precoma and coma conditions, and on a
      thorough study of the specialized (especially Romanian) literature. Also, we used
      validated scientific proof of torture in conditions of lack of light. RESULTS: We
      found a perfect interpenetration between the ARAS and the following two
      complementary subsystems: 1. The hypothalamic suprachiasmatic nucleus, that has
      the role of coordinating the periodicity of some biological functions depending
      on the circadian rhythm; and 2. The main photoperiodic organ, the pineal gland
      (epiphysis), which together with the ARAS has a role in the photoperiodicity
      modulation of some biological functions during the state of vigilance.

PMID- 25071309
TI  - Reduction of IL-20 Expression in Rheumatoid Arthritis by Linear Polarized
      Infrared Light Irradiation.
AB  - BACKGROUND: Low-level laser is being evaluated for treating rheumatoid arthritis
      (RA). Recently, the linear polarized infrared light (Super Lizer, SL) irradiation
      may also be useful for RA treatment. However, the molecular mechanism underlying
      the effectiveness of SL on RA is unclear. It has been IL-20 may involved in RA
      disease progression. AIM: To understand how SL action, we constructed the
      experimental model in vitro using human rheumatoid fibroblast-like synoviocyte
      (MH7A) and collagen induced (CIA) RA rat in vivo. We examined the effect of SL
      irradiation on IL-20 gene expression in MH7A and IL-20 protein production in CIA)
      rat joints. MATERIALS AND METHODS: MH7A was cultured and challenged with IL
      1beta, then examined IL-20 and IL-20R mRNA level by DNA microarray. IL-20 protein
      expression was examined by immunohistochemistry using a specific antibody against
      rat IL-20. RESULT: Scatter plot analysis demonstrated that an increase in IL-20
      gene expression by IL-1beta was reduced by SL irradiation, but IL-20R did not
      show a significant change. The Immunohistochemical analysis demonstrated a strong
      IL-20 staining in synovial membrane tissue of CIA rat joint, and SL irradiation
      significantly reduced the staining. DISCUSSION: Since IL-20 has been identified
      as an important cytokine in the pathogenesis of RA, the reduction of IL-20
      expression by SL irradiation may be one of mechanisms in reduction of
      inflammation in RA joints by SL irradiation suggesting that SL irradiation may be
      useful for RA therapy.

PMID- 25071310
TI  - Photodynamic Therapy with 5% delta-Aminolevulinic Acid is Safe and Effective
      Treatment of Acne Vulgaris in Japanese Patients.
AB  - BACKGROUND AND AIMS: Photodynamic therapy with aminolevulinic acid (ALA-PDT) is
      effective therapy for acne vulgaris; however, relatively strong side effects
      limit its wide usage. We have previously demonstrated that ALA-induced
      protoporphyrin IX distribution with lower concentrations and shorter contact time
      of ALA resulted in focused damage in sebaceous glands in vivo. We have formulated
      a protocol for ALA-PDT using 5% ALA with 2 hours contact time. The objective of
      this study was to establish the effectiveness and side effect profile of the new
      protocol in humans. SUBJECTS AND METHODS: Eleven Japanese patients (Fitzpatrick's
      skin type III - IV, mean age 23.7+/-7.2) with facial acne received topical
      application of 5% ALA for 2 hours with subsequent illumination by a broadband
      light (600 - 1100 nm, 15J/cm(2), 60 mW/cm(2)). Subjects were evaluated prior to
      the procedure, 1 month, and 3 months after the treatment by a blinded
      dermatologist using the global acne grading system (GAGS). Side effects were
      monitored through the treatment period. RESULTS: The mean GAGS score decreased
      from 22.1+/-3.8 at baseline to 19.4 at 1 month, and to 16.3 at 3 months after PDT
      (P<0.05). Ten of eleven patients experienced local side effects, such as
      erythema, which were of minimal to mild severity. However, most side effects were
      of minimal to mild severity, and all of them resolved within several days without
      post inflammatory hyper pigmentation. CONCLUSION: Our protocol was effective for
      acne in Japanese and did not exhibit severe side effects.

PMID- 25071311
TI  - Investigation regarding prevention of insufficiency fractures in children with
      severe cerebral palsy by Light-Emitting Diode (LED) irradiation.
AB  - Bone metabolism in children with severe fractures was examined, risk factors for
      fractures were characterized, and effects of LED (light-emitting diode)
      irradiation on the risk factors for fractures were investigated. Since
      insufficiency fracture in children with severe cerebral palsy can be caused
      without obvious external force in daily care, it is sometimes handled as a
      medical accident and can lead to a lawsuit. It is very important to explain the
      possibility of an insufficiency fracture to guardians before a fracture is
      caused. However, risk factors for fractures in bone metabolism has not been well
      investigated and preventive treatment of fractures have also not been
      established. Risk factors in bone metabolism were investigated in 14 cases of
      insufficiency fracture in children with severe cerebral palsy accompanied by
      akathisia in this study. Fractures were likely caused around 8 years old when
      children grew rapidly, and either IGF-1 or BAP showed low values in all cases. A
      group with LED irradiation consisting of 25 cases indicated a normal value of IGF
      1 related to bone growth, BAP related to bone density and NTX/Cr. A case
      irradiated to LED for more than one month clearly showed normal bone metabolism
      compared with the change within a non irradiated group after one year. LED
      irradiation increased bone density and femur cortical bone thickness, and
      improved bone age. Adequate effects were not seen in two children at 14 years of
      age. The commercially available LED light bulbs that we used have a peak at 446
      477 nm in the blue wave length, but also have second peaks at 574 nm in green, at
      590 nm in yellow, and even 612 nm in orange and 660 nm in red are included.
      Although it is thought that such a variety of wave lengths might have a good
      influence on bone metabolism; exposure time and distance, number of regions, and
      time period irradiated to LED are important factors, since the LED power density
      is low (0.9 mW/m(2) with a 30 cm distance). Our results suggest that LED
      irradiation can be a phototherapy to activate human homeostasis. 

PMID- 25071312
TI  - Treatment of Vaginal Relaxation Syndrome with an Erbium:YAG Laser Using 90
      degrees  and 360 degrees  Scanning Scopes: A Pilot Study & Short-term Results.
AB  - BACKGROUND AND AIMS: Vaginal relaxation syndrome (VRS) is both a physical and
      psychological problem for women and often their partners. Recently the 2940 nm
      Er:YAG laser has attracted attention for VRS treatment. The current study
      evaluated the clinical efficacy of this nonsurgical laser procedure. SUBJECTS AND
      METHODS: Thirty postpartum females with VRS or vaginal atrophy, ages from 33 - 56
      yr (mean 41.7 yr) were divided randomly into two groups, Group A and Group B.
      Both groups were treated for 4 sessions at 1~2-weekly intervals with a 2940 nm
      Er:YAG via 90 degrees  and 360 degrees  scanning scopes. In Group A the first 2
      sessions were performed with the 360 degrees  scope and the final 2 with the 90
      degrees  scope in multiple micropulse mode, 1.7 J delivered per shot, 3
      multishots, 3 passes per session. Group B underwent multiple micropulse mode
      treatment with the 90 degrees  scope in all 4 sessions (same parameters as Group
      A) then during the final 2 sessions an additional 2 passes/session were delivered
      with the 360 degrees  scope, long-pulsed mode, 3.7 J delivered per shot.
      Perineometer assessments were performed at baseline and at 2 months post
      treatment for vaginal tightness. Histological specimens were taken at baseline
      and at 2 months post-procedure. Subjective satisfaction with vaginal tightening
      was assessed together with improvement in sexual satisfaction. RESULTS were
      tested for statistical significance with the paired Student's t-test. RESULTS:
      All subjects successfully completed the study with no adverse events. Significant
      improvement in vaginal wall relaxation was seen in all subjects at 2 months post
      procedure based on the perineometer values, on the partners' input for vaginal
      tightening (76.6%) and for sexual satisfaction as assessed by the subjects
      themselves (70.0%). The histological findings suggested better elasticity of the
      vaginal wall with tightening and firming. CONCLUSIONS: Both regimens of Er:YAG
      laser treatment for VRS produced significant improvement in vaginal relaxation.
      With multishots delivered in the multiple micropulse mode via scanning scopes,
      nonsurgical Er:YAG laser treatment was pain-free, safe, side effect free, easily
      tolerated and effective.

PMID- 25071313
TI  - Xylem and phloem phenology in co-occurring conifers exposed to drought.
AB  - KEY MESSAGE: Variability in xylem and phloem phenology among years and species is
      caused by contrasting temperatures prevailing at the start of the growing season
      and species-specific sensitivity to drought. ABSTRACT: The focus of this study
      was to determine temporal dynamics of xylem and phloem formation in co-occurring
      deciduous and evergreen coniferous species in a dry inner Alpine environment (750
      m a.s.l., Tyrol, Austria). By repeated micro-sampling of the stem, timing of key
      phenological dates of xylem and phloem formation was compared among mature Pinus
      sylvestris, Larix decidua and Picea abies during two consecutive years. Xylem
      formation in P. sylvestris started in mid and late April 2011 and 2012,
      respectively, and in both years about 2 week later in P. abies and L. decidua.
      Phloem formation preceded xylem formation on average by 3 week in P. sylvestris,
      and c. 5 week in P. abies and L. decidua. Based on modeled cell number increase,
      tracheid production peaked between early through late May 2011 and late May
      through mid-June 2012. Phloem formation culminated between late April and mid-May
      in 2011 and in late May 2012. Production of xylem and phloem cells continued for
      about 4 and 5-6 months, respectively. High variability in xylem increment among
      years and species is related to exogenous control by climatic factors and species
      specific sensitivity to drought, respectively. On the other hand, production of
      phloem cells was quite homogenous and showed asymptotic decrease with respect to
      xylem cells indicating endogenous control. Results indicate that onset and
      culmination of xylem and phloem formation are controlled by early spring
      temperature, whereby strikingly advanced production of phloem compared to xylem
      cells suggests lower temperature requirement for initiation of the former.

PMID- 25071314
TI  - Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver
      disease?
AB  - It was estimated that from 2002 to 2008 the risk of developing cancer increased a
      quarter-fold in men and two-fold in women due to excessive BMI. Obesity,
      metabolic syndrome and type 2 diabetes mellitus are strictly related and are key
      pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most
      frequent liver disease worldwide. The most important consequence of the
      "metabolic epidemics" is the probable rise in the incidence of hepatocarcinoma
      (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a
      storage organ where lipids are preserved as an energy source. It is an active
      organ with important endocrine, paracrine, and autocrine actions in addition to
      immune functions. Adipocytes produce a wide range of hormones, cytokines, and
      growth factors that can act locally in the adipose tissue microenvironment and
      systemically. In this article, the main roles of insulin growth factor (IGF)-1
      and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it
      may also act in early hepato-carcinogenesis, as pre-neoplastic lesions express
      IGF-2 mRNA. IGF-1 and IGF-2 interact with specific receptors (IGF-1R and IGF-2R).
      IGF-1R is over-expressed in in vitro and in animal models of HCC and it was
      demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R
      and that it was involved in the degeneration of pre-neoplastic lesions via an
      increase in their mitotic activity. Both IGF-2R and TGF beta, a growth inhibitor,
      levels are reduced in human HCC compared with adjacent normal liver tissues.
      Another key mechanism involves peroxisome proliferator-activated receptor
      (PPAR)gamma. In in vitro studies, PPARgamma inhibited various carcinomas
      including HCC, most probably by regulating apoptosis via the p21, p53 and p27
      pathways. Finally, as a clinical consequence, to improve survival, efforts to
      achieve a "healthier diet" should be promoted by physicians and politicians. 

PMID- 25071315
TI  - Androgen receptor signaling in hepatocellular carcinoma and pancreatic cancers.
AB  - Hepatocellular carcinoma (HCC) and pancreatic cancer remain difficult to treat,
      and despite the ongoing development of new treatments, the overall survival rate
      has only modestly improved over the past decade. Liver and pancreatic progenitors
      commonly develop from endoderm cells in the embryonic foregut. A previous study
      showed that HCC and pancreatic cancer cell lines variably express androgen
      receptor (AR), and these cancers and the surrounding tissues also express AR. AR
      is a ligand-dependent transcription factor that belongs to the nuclear receptor
      superfamily. Androgen response element is present in regulatory elements on the
      AR-responsive target genes, such as transforming growth factor beta-1 (TGF beta
      1) and vascular endothelial growth factor (VEGF). It is well known that the
      activation of AR is associated with human carcinogenesis in prostate cancer as
      well as HCC and pancreatic cancer and that GRP78, TGF beta, and VEGF all play
      important roles in carcinogenesis and cancer development in these cancers. HCC is
      a male-dominant cancer irrespective of its etiology. Previous work has reported
      that vertebrae forkhead box A 1/2 are involved in estrogen receptors and/or AR
      signaling pathways, which may contribute to the gender differences observed with
      HCC. Our recent work also showed that AR has a critical role in pancreatic cancer
      development, despite pancreatic cancer not being a male dominant cancer. Aryl
      hydrocarbon (or dioxin) receptor is also involved in both HCC and pancreatic
      cancer through the formation of complex with AR. It is possible that AR might be
      involved in their carcinogenesis through major histocompatibility complex class I
      chain-related gene A/B. This review article describes AR and its role in HCC and
      pancreatic cancer and suggests that more specific AR signaling-inhibitors may be
      useful in the treatment of these "difficult to treat" cancers.

PMID- 25071316
TI  - Hepatectomy for hepatocellular carcinoma in the era of liver transplantation.
AB  - The aim of management of hepatocellular carcinoma (HCC) is to improve the
      prognosis of the patients by radical resection and preserve remnant liver
      function. Although liver transplantation is associated with a lower tumor
      recurrence rate, this benefit is counteracted by long-term complications.
      Therefore, hepatectomy could be the first choice of treatment in selected
      patients with HCC. However, the higher frequency of tumor recurrence and the
      lower rate of resectability after hepatectomy for HCC led to an unsatisfactory
      prognosis. New strategies are required to improve the long-term outcome of HCC
      after hepatectomy. In this paper, we introduce some strategies to increase the
      low rate of resectability and reduce the high rate of tumor recurrence. Some
      aggressive treatments for tumor recurrence to extend long-term survival are also
      involved. We believe that hepatectomy combined with other therapies, such as
      portal vein embolization, transarterial chemoembolization, radioembolization,
      antiviral treatment, radiofrequency ablation and salvage transplantation, is a
      promising treatment modality for HCC and may improve survival greatly. 

PMID- 25071317
TI  - Polymorphisms in the IFNL3/IL28B gene and hepatitis C: from adults to children.
AB  - The purpose of the present review is to summarise the current knowledge on the
      association between single nucleotide polymorphisms (SNPs) in the interferon L3
      (IFNL3) gene and hepatitis C virus (HCV) infection in children. Many studies in
      adults have demonstrated that genetic variation in IFNL3 is a strong predictor of
      the virological response in treatment-naive patients with HCV genotype 1 who were
      treated with Pegylated-IFN-alpha and ribavirin. Genetic variation in IFNL3 is
      also associated with the spontaneous clearance of HCV. Thus far, few paediatric
      studies have explored the association between variations in the IFNL3 gene and
      either spontaneous or treatment-induced clearance of HCV. The CC genotype of the
      rs12979860 SNP is associated with the spontaneous clearance of HCV in children
      independently of HCV genotype. Four paediatric studies have shown that both the
      CC genotype of the rs12979860 SNP and the TT genotype of the rs8099917 SNP are
      associated with the treatment-induced (IFN monotherapy and Pegylated-IFN-alpha
      and ribavirin association) clearance of HCV, while the rs12980275 SNP did not
      affect the virological response. The possible role of IFNL3 gene variation as a
      pre-treatment and on-treatment predictor of virological response in children is
      highly attractive but still undetermined. Further paediatric studies are needed
      to evaluate if testing for SNPs in IFNL3, either alone or together with other
      predictors of response to treatment, could be used to direct treatment
      strategies, including an avoidance of unnecessary protease inhibitor therapy and
      the duration of treatment. 

PMID- 25071318
TI  - Hepatitis C virus reinfection after liver transplantation: is there a role for
      direct antiviral agents?
AB  - Recurrence of hepatitis C virus (HCV) infection following liver transplantation
      (LT) is almost universal and can accelerate graft cirrhosis in up to 30% of
      patients. The development of effective strategies to treat or prevent HCV
      recurrence after LT remains a major challenge, considering the shortage of donor
      organs and the accelerated progression of HCV in LT recipients. Standard
      antiviral therapy with pegylated-interferon plus ribavirin is the current
      treatment of choice for HCV LT recipients, even though the combination is not as
      effective as it is in immunocompetent patients. A sustained virological response
      in the setting of LT improves patient and graft survival, but this is only
      achieved in 30%-45% of patients and the treatment is poorly tolerated. To improve
      the efficacy of pre- and post-transplant antiviral therapy, a new class of potent
      direct-acting antiviral agents (DAAs) has been developed. The aim of this review
      is to summarize the use of DAAs in LT HCV patients. PubMed, Cochrane Library,
      MEDLINE, EMBASE, Web of Science and clinical trial databases were searched for
      this purpose. To date, only three clinical studies on the topic have been
      published and most of the available data are in abstract form. Although a
      moderately successful early virological response has been reported, DAA treatment
      regimens were associated with severe toxicity mitigating their potential
      usefulness. Moreover, the ongoing nature of data, the lack of randomized studies,
      the small number of enrolled patients and the heterogeneity of these studies make
      the results largely anecdotal and questionable. In conclusion, large well
      designed clinical studies on DAAs in HCV LT patients are required before these
      drugs can be recommended after transplantation. 

PMID- 25071319
TI  - Cytokinome profile evaluation in patients with hepatitis C virus infection.
AB  - The ''omics sciences'' (genomics, transcriptomics, proteomics) are often used to
      study living organisms as a whole system by evaluating the complex expression
      patterns of genes, miRNA, proteins, and metabolites. This study aimed, through
      bioinformatics and systems biology, to decipher the cytokinome profile in the
      evolution of inflammatory processes leading to cancer. The cytokinome was defined
      as the totality of cytokines and their interactions in and around biological
      cells. The system biology approach would provide a better understanding of the
      complex interaction network of cytokines, especially in cancer patients. Acquired
      knowledge would enable health providers with tools to evaluate disease onset
      through progression as well as identifying innovative therapeutic strategies.
      Understanding the role each cytokine plays in the metabolic network is of great
      importance. This paper reviews our group's ''omics'' work. In particular, it
      addresses the role cytokines play in liver disease in six different scenarios.
      The first is the role the cytokines play in chronic inflammatory diseases and
      cancers. The second is the significance of the cytokinome profile. The third is
      the role of liver cirrhosis as an inflammatory disease. The fourth is the
      comparison of cytokine levels evaluated in patients with chronic hepatitis C
      virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of
      cytokine levels evaluated in patients with HCV-related cirrhosis in the presence
      and absence of type 2 diabetes. And lastly, we present a comparison of cytokine
      levels evaluated in patients with HCV-related cirrhosis in the presence and
      absence of hepatocellular carcinoma. 

PMID- 25071321
TI  - Approaches to improve quality of care in inflammatory bowel diseases.
AB  - Studies across medical disciplines have shown gaps in the care recommended in
      evidence based guidelines and the care actually delivered. Quality improvement
      projects using systematic audit and feedback interventions such as quality
      measures, will become increasingly important tools to address these gaps in care.
      These gaps are also apparent in the care of patients with inflammatory bowel
      disease. Multiple organizations, including the American Gastroenterology
      Association and the Crohn's and Colitis Foundation of America, have developed
      programs designed to implement quality measures to improve the care of
      inflammatory bowel disease (IBD) patients. Early results show promise of
      improving quality, but numerous barriers remain. Gastroenterologists need to be
      aware of these processes to provide the highest care possible to patients with
      IBD. We review the existing literature on approaches to quality improvement and
      their potential application and barriers when applied to IBD care. 

PMID- 25071320
TI  - Epidemiology and natural history of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) affects 130-210 million people worldwide and is one of
      the major risk factors for hepatocellular carcinoma. Globally, at least one third
      of hepatocellular carcinoma cases are attributed to HCV infection, and 350000
      people died from HCV related diseases per year. There is a great geographical
      variation of HCV infection globally, with risk factors for the HCV infection
      differing in various countries. The progression of chronic hepatitis C to end
      stage liver disease also varies in different study populations. A long-term
      follow-up cohort enrolling participants with asymptomatic HCV infection is
      essential for elucidating the natural history of HCV-caused hepatocellular
      carcinoma, and for exploring potential seromarkers that have high predictability
      for risk of hepatocellular carcinoma. However, prospective cohorts comprising
      individuals with HCV infection are still uncommon. The risk evaluation of viral
      load elevation and associated liver disease/cancer in HCV (REVEAL-HCV) study has
      followed a cohort of 1095 residents seropositive for antibodies against hepatitis
      C virus living in seven townships in Taiwan for more than fifteen years. Most of
      them have acquired HCV infection through iatrogenic transmission routes. As the
      participants in the REVEAL-HCV study rarely receive antiviral therapies, it
      provides a unique opportunity to study the natural history of chronic HCV
      infection. In this review, the prevalence, risk factors and natural history of
      HCV infection are comprehensively reviewed. The study cohort, data collection,
      and findings on liver disease progression of the REVEAL-HCV study are described. 

PMID- 25071322
TI  - Update on the prevention of local recurrence and peritoneal metastases in
      patients with colorectal cancer.
AB  - The prevention of a disease process has always been superior to the treatment of
      the same disease throughout the history of medicine and surgery. Local recurrence
      and peritoneal metastases occur in approximately 8% of colon cancer patients and
      25% of rectal cancer patients and should be prevented. Strategies to prevent
      colon or rectal cancer local recurrence and peritoneal metastases include
      cytoreductive surgery and hyperthermic perioperative chemotherapy (HIPEC). These
      strategies can be used at the time of primary colon or rectal cancer resection if
      the HIPEC is available. At institutions where HIPEC is not available with the
      treatment of primary malignancy, a proactive second-look surgery is recommended.
      Several phase II studies strongly support the proactive approach. If peritoneal
      metastases were treated along with the primary colon resection, 5-year survival
      was seen and these results were superior to the results of treatment after
      peritoneal metastases had developed as recurrence. Also, prophylactic HIPEC
      improved survival with T3/T4 mucinous or signet ring colon cancers. A second-look
      has been shown to be effective in two published manuscripts. Unpublished data
      from MedStar Washington Cancer Institute also produced favorable date. Rectal
      cancer with peritoneal metastases may not be so effectively treated. There are
      both credits and debits of this proactive approach. Selection factors should be
      reviewed by the multidisciplinary team for individualized management of patients
      with or at high risk for peritoneal metastases. 

PMID- 25071323
TI  - Familial colorectal cancer: a review.
AB  - Familial colorectal cancer constitutes a heterogeneous group of patients in whom
      the underlying molecular mechanism is still unknown. Predisposition to a such
      neoplasms in this setting seems to be due to common low-penetrance genetic
      components, but the role of genetic testing in clinical practice has to be
      determined. Although screening guidelines in this moderate-risk population are
      empiric, data obtained in epidemiologic, meta-analyses and cohort studies and,
      more recently, the increased risk of advanced adenomas in first degree relatives
      who underwent screening colonoscopy support the need to include these individuals
      in specific screening programs. However, data to determine what test to use, how
      often to use and which organizational strategy to implement are needed. At
      present, screening uptake in this population is less than optimal; offering the
      opportunity to access to screening and improving screening uptake is a first
      significant step. 

PMID- 25071325
TI  - Diagnosing Helicobacter pylori infection in vivo by novel endoscopic techniques.
AB  - Infection with Helicobacter pylori (H. pylori) is a worldwide problem. Endoscopic
      observation of H. pylori infection in vivo would be helpful to obtain an
      immediate diagnosis. The aim of this review is to describe recent advances in
      endoscopic technology and to review the available literature pertaining to its
      clinical application in H. pylori infection. Endoscopic visualization of H.
      pylori infection is not always feasible using conventional endoscopy. Thus,
      advanced endoscopic techniques have been developed with the aim of providing a
      precise and ''real-time'' endoscopic diagnosis. Recently, new endoscopic
      techniques such as magnifying endoscopy, narrow band imaging, I-Scan,
      endocytoscopy and endomicroscopy help focus examination of the stomach to
      diagnose disease in a time-efficient manner, and the analysis of mucosal surface
      details is beginning to resemble histologic examination. The new detailed images
      have enabled endoscopists to observe microscopic structures, such as gastric pit
      patterns, microvessels and cell morphology. Accordingly, endoscopic prediction of
      H. pylori infection is possible by analysis of surface architecture of the
      mucosa, which influences the clinical management. These endoscopic techniques
      might lead us to easier diagnosis and treatment of H. pylori-related diseases. 

PMID- 25071324
TI  - Helicobacter pylori infection - recent developments in diagnosis.
AB  - Considering the recommended indications for Helicobacter pylori (H. pylori)
      eradication therapy and the broad spectrum of available diagnostic methods, a
      reliable diagnosis is mandatory both before and after eradication therapy. Only
      highly accurate tests should be used in clinical practice, and the sensitivity
      and specificity of an adequate test should exceed 90%. The choice of tests should
      take into account clinical circumstances, the likelihood ratio of positive and
      negative tests, the cost-effectiveness of the testing strategy and the
      availability of the tests. This review concerns some of the most recent
      developments in diagnostic methods of H. pylori infection, namely the
      contribution of novel endoscopic evaluation methodologies for the diagnosis of H.
      pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In
      addition, the diagnostic contribution of histology and the urea breath test was
      explored recently in specific clinical settings and patient groups. Recent
      studies recommend enhancing the number of biopsy fragments for the rapid urease
      test. Bacterial culture from the gastric biopsy is the gold standard technique,
      and is recommended for antibiotic susceptibility test. Serology is used for
      initial screening and the stool antigen test is particularly used when the urea
      breath test is not available, while molecular methods have gained attention
      mostly for detecting antibiotic resistance. 

PMID- 25071326
TI  - Gastroretentive drug delivery systems for the treatment of Helicobacter pylori.
AB  - Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial
      infections and is found in the stomachs of approximately half of the world's
      population. It is the primary known cause of gastritis, gastroduodenal ulcer
      disease and gastric cancer. However, combined drug therapy as the general
      treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse
      reactions and poor patient compliance are major obstacles to the eradication of
      H. pylori. Oral site-specific drug delivery systems that could increase the
      longevity of the treatment agent at the target site might improve the therapeutic
      effect and avoid side effects. Gastroretentive drug delivery systems potentially
      prolong the gastric retention time and controlled/sustained release of a drug,
      thereby increasing the concentration of the drug at the application site,
      potentially improving its bioavailability and reducing the necessary dosage.
      Recommended gastroretentive drug delivery systems for enhancing local drug
      delivery include floating systems, bioadhesive systems and expandable systems. In
      this review, we summarize the important physiological parameters of the
      gastrointestinal tract that affect the gastric residence time. We then focus on
      various aspects useful in the development of gastroretentive drug delivery
      systems, including current trends and the progress of novel forms, especially
      with respect to their application for the treatment of H. pylori infections. 

PMID- 25071327
TI  - Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and
      clinical presentations.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the
      world. Presentation of the disease ranges from simple steatosis to non-alcoholic
      steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome
      that includes central abdominal obesity along with other components. Up to 80% of
      patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2).
      However, the distribution of fat tissue plays a greater role in insulin
      resistance than the BMI. The large amount of visceral adipose tissue (VAT) in
      morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of
      NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources
      and de novo lipogenesis, are released to the portal venous system. Excess free
      fatty acids and chronic low-grade inflammation from VAT are considered to be two
      of the most important factors contributing to liver injury progression in NAFLD.
      In addition, secretion of adipokines from VAT as well as lipid accumulation in
      the liver further promotes inflammation through nuclear factor kappa B signaling
      pathways, which are also activated by free fatty acids, and contribute to insulin
      resistance. Most NAFLD patients are asymptomatic on clinical presentation, even
      though some may present with fatigue, dyspepsia, dull pain in the liver and
      hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction
      through lifestyle modifications, anti-obesity medication and bariatric surgery.
      This article reviews the available information on the biochemical and metabolic
      phenotypes associated with obesity and fatty liver disease. The relative
      contribution of visceral and liver fat to insulin resistance is discussed, and
      recommendations for clinical evaluation of affected individuals is provided. 

PMID- 25071328
TI  - Role of diet and lifestyle changes in nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes
      of liver disease worldwide and has been recognized as a major health burden. The
      prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary
      lifestyle, unhealthy dietary pattern, and metabolic syndrome. Currently, there is
      no drug therapy that can be formulated for treating NAFLD. A combination of
      dietary modifications and increased physical activity remains the mainstay of
      NAFLD management. It is hard to maintain this mode of management; however, it
      seems to have significant long-term benefits. Furthermore, NAFLD patients,
      whether obese or not, should be educated that a healthy diet and physical
      activity have benefits beyond weight reduction. Further large controlled
      randomized trials are needed in order to identify the best dietary regimen and
      physical activity in the management of NAFLD patients. This review highlights the
      role of diet and lifestyle modifications in the management of NAFLD, and focuses
      on human studies regarding dietary modifications and physical activity. 

PMID- 25071329
TI  - Managing malignant biliary obstruction in pancreas cancer: choosing the
      appropriate strategy.
AB  - Most patients with pancreatic cancer develop malignant biliary obstruction.
      Treatment of obstruction is generally indicated to relieve symptoms and improve
      morbidity and mortality. First-line therapy consists of endoscopic biliary stent
      placement. Recent data comparing plastic stents to self-expanding metallic stents
      (SEMS) has shown improved patency with SEMS. The decision of whether to treat
      obstruction and the means for doing so depends on the clinical scenario. For
      patients with resectable disease, preoperative biliary decompression is only
      indicated when surgery will be delayed or complications of jaundice exist. For
      patients with locally advanced disease, self-expanding metal stents are superior
      to plastic stents for long-term patency. For patients with advanced disease, the
      choice of metallic or plastic stent depends on life expectancy. When endoscopic
      stent placement fails, percutaneous or surgical treatments are appropriate.
      Endoscopic therapy or surgical approach can be used to treat concomitant duodenal
      and biliary obstruction. 

PMID- 25071330
TI  - Pancreatic cancer: advances in treatment.
AB  - Pancreatic cancer is a leading cause of cancer mortality and the incidence of
      this disease is expected to continue increasing. While patients with pancreatic
      cancer have traditionally faced a dismal prognosis, over the past several years
      various advances in diagnosis and treatment have begun to positively impact this
      disease. Identification of effective combinations of existing chemotherapeutic
      agents, such as the FOLFIRINOX and the gemcitabine + nab-paclitaxel regimen, has
      improved survival for selected patients although concerns regarding their
      toxicity profiles remain. A better understanding of pancreatic carcinogenesis has
      identified several pre-malignant precursor lesions, such as pancreatic
      intraepithelial neoplasias, intraductal papillary mucinous neoplasms, and cystic
      neoplasms. Imaging technology has also evolved dramatically so as to allow early
      detection of these lesions and thereby facilitate earlier management. Surgery
      remains a cornerstone of treatment for patients with resectable pancreatic
      tumors, and advances in surgical technique have allowed patients to undergo
      resection with decreasing perioperative morbidity and mortality. Surgery has also
      become feasible in selected patients with borderline resectable tumors as a
      result of neoadjuvant therapy. Furthermore, pancreatectomy involving vascular
      reconstruction and pancreatectomy with minimally invasive techniques have
      demonstrated safety without significantly compromising oncologic outcomes.
      Lastly, a deeper understanding of molecular aberrations contributing to the
      development of pancreatic cancer shows promise for future development of more
      targeted and safe therapeutic agents. 

PMID- 25071331
TI  - Cachexia and pancreatic cancer: are there treatment options?
AB  - Cachexia is frequently described in patients with pancreatic ductal
      adenocarcinoma (PDAC) and is associated with reduced survival and quality of
      life. Unfortunately, the therapeutic options of this multi-factorial and complex
      syndrome are limited. This is due to the fact that, despite extensive preclinical
      and clinical research, the underlying pathological mechanisms leading to PDAC
      associated cachexia are still not fully understood. Furthermore, there is still a
      lack of consensus on the definition of cachexia, which complicates the
      standardization of diagnosis and treatment as well as the analysis of the current
      literature. In order to provide an efficient therapy for cachexia, an early and
      reliable diagnosis and consistent monitoring is required, which can be
      challenging especially in obese patients. Although many substances have been
      tested in clinical and preclinical settings, so far none of them have been proven
      to have a long-term effect in ameliorating cancer-associated cachexia. However,
      recent studies have demonstrated that multidimensional therapeutic modalities are
      able to alleviate pancreatic cancer-associated cachexia and ultimately improve
      patients' outcome. In this current review, we propose a stepwise and pragmatic
      approach to facilitate and standardize the treatment of cachexia in pancreatic
      cancer patients. This strategy consists of nutritional, dietary, pharmacological,
      physical and psychological methods. 

PMID- 25071332
TI  - Neoadjuvant strategies for pancreatic cancer.
AB  - Pancreatic cancer (PC) is the fourth cause of cancer death in Western countries,
      the only chance for long term survival is an R0 surgical resection that is
      feasible in about 10%-20% of all cases. Five years cumulative survival is less
      than 5% and rises to 25% for radically resected patients. About 40% has locally
      advanced in PC either borderline resectable (BRPC) or unresectable locally
      advanced (LAPC). Since LAPC and BRPC have been recognized as a particular form of
      PC neoadjuvant therapy (NT) has increasingly became a valid treatment option. The
      aim of NT is to reach local control of disease but, also, it is recognized to
      convert about 40% of LAPC patients to R0 resectability, thus providing a
      significant improvement of prognosis for responding patients. Once R0 resection
      is achieved, survival is comparable to that of early stage PCs treated by upfront
      surgery. Thus it is crucial to look for a proper patient selection. Neoadjuvant
      strategies are multiples and include neoadjuvant chemotherapy (nCT), and the
      association of nCT with radiotherapy (nCRT) given as either a combination of a
      radio sensitizing drug as gemcitabine or capecitabine or and concomitant
      irradiation or as upfront nCT followed by nRT associated to a radio sensitizing
      drug. This latter seem to be most promising as it may select patients who do not
      go on disease progression during initial treatment and seem to have a better
      prognosis. The clinical relevance of nCRT may be enhanced by the application of
      higher active protocols as FOLFIRINOX. 

PMID- 25071333
TI  - Therapeutic applications of curcumin for patients with pancreatic cancer.
AB  - A number of preclinical studies have demonstrated anticancer effects for curcumin
      in various types of tumors, including pancreatic cancer. Curcumin has anticancer
      effects both alone and in combination with other anticancer drugs (e.g.,
      gemcitabine, 5-fluorouracil, and oxaliplatin), and it has been shown to modulate
      a variety of molecular targets in preclinical models, with more than 30 molecular
      targets identified to date. Of these various molecules, NF-kappaB is thought to
      be one of the primary targets of curcumin activity. Based on these promising
      preclinical results, several research groups, including our own, have progressed
      to testing the anticancer effects of curcumin in clinical trials; however, the
      poor bioavailability of this agent has been the major challenge for its clinical
      application. Despite the ingestion of gram-level doses of curcumin, plasma
      curcumin levels remain at low (ng/mL) levels in patients, which is insufficient
      to yield the anticancer benefits of curcumin. This problem has been solved by the
      development of highly bioavailable forms of curcumin (THERACURMIN), and higher
      plasma curcumin levels can now be achieved without increased toxicity in patients
      with pancreatic cancer. In this article, we review possible therapeutic
      applications of curcumin in patients with pancreatic cancer.

PMID- 25071334
TI  - Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and
      progression.
AB  - Pim-3 is a member of the provirus integration site for Moloney murine leukemia
      virus (Pim) family proteins that exhibit serine/threonine kinase activity.
      Similar to the other Pim kinases (Pim-1 and Pim-2), Pim-3 is involved in many
      cellular processes, including cell proliferation, survival, and protein
      synthesis. Although Pim-3 is expressed in normal vital organs, it is
      overexpressed particularly in tumor tissues of endoderm-derived organs, including
      the liver, pancreas, and colon. Silencing of Pim-3 expression can retard in vitro
      cell proliferation of hepatocellular, pancreatic, and colon carcinoma cell lines
      by promoting cell apoptosis. Pim-3 lacks the regulatory domains similarly as Pim
      1 and Pim-2 lack, and therefore, Pim-3 can exhibit its kinase activity once it is
      expressed. Pim-3 expression is regulated at transcriptional and post
      transcriptional levels by transcription factors (e.g., Ets-1) and post
      translational modifiers (e.g., translationally-controlled tumor protein),
      respectively. Pim-3 could promote growth and angiogenesis of human pancreatic
      cancer cells in vivo in an orthotopic nude mouse model. Furthermore, a Pim-3
      kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells
      were injected into nude mice, without inducing any major adverse effects. Thus,
      Pim-3 kinase may serve as a novel molecular target for developing targeting drugs
      against pancreatic and other types of cancer. 

PMID- 25071335
TI  - Role of non-coding RNAs in pancreatic cancer: the bane of the microworld.
AB  - Our understanding of the mechanisms underlying the development of pancreatic
      cancer has been greatly advanced. However, the molecular events involved in the
      initiation and development of pancreatic cancer remain inscrutable. None of the
      present medical technologies have been proven to be effective in significantly
      improving early detection or reducing the mortality/morbidity of this disease.
      Thus, a better understanding of the molecular basis of pancreatic cancer is
      required for the identification of more effective diagnostic markers and
      therapeutic targets. Non-coding RNAs (ncRNAs), generally including microRNAs and
      long non-coding RNAs, have recently been found to be deregulated in many human
      cancers, which provides new opportunities for identifying both functional drivers
      and specific biomarkers of pancreatic cancer. In this article, we review the
      existing literature in the field documenting the significance of aberrantly
      expressed and functional ncRNAs in human pancreatic cancer, and discuss how
      oncogenic ncRNAs may be involved in the genetic and epigenetic networks
      regulating functional pathways that are deregulated in this malignancy,
      particularly of the ncRNAs' role in drug resistance and epithelial-mesenchymal
      transition biological phenotype, with the aim of analyzing the feasibility of
      clinical application of ncRNAs in the diagnosis and treatment of pancreatic
      cancer. 

PMID- 25071336
TI  - Atypical causes of cholestasis.
AB  - Cholestatic liver disease consists of a variety of disorders. Primary sclerosing
      cholangitis and primary biliary cirrhosis are the most commonly recognized
      cholestatic liver disease in the adult population, while biliary atresia and
      Alagille syndrome are commonly recognized in the pediatric population. In
      infants, the causes are usually congenital or inherited. Even though jaundice is
      a hallmark of cholestasis, it is not always seen in adult patients with chronic
      liver disease. Patients can have "silent" progressive cholestatic liver disease
      for years prior to development of symptoms such as jaundice and pruritus. In this
      review, we will discuss some of the atypical causes of cholestatic liver disease
      such as benign recurrent intrahepatic cholestasis, progressive familial
      intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral
      nutrition induced cholestasis and cholestasis secondary to drug induced liver
      injury. 

PMID- 25071338
TI  - Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory
      drugs and/or low-dose aspirin use: old question new insights.
AB  - Previous reports clearly demonstrated that Helicobacter pylori (H. pylori)
      infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA)
      use significantly and independently increased the risk for the development of
      peptic ulcer disease. Today, the presence of H. pylori infection associated with
      low dose ASA and/or NSAID use in the same patient is becoming more frequent and
      therefore the potential interaction between these factors and the consequences of
      it has important implications. Whether NSAID intake in the presence of H. pylori
      infection may further increase the risk of peptic ulcer carried by the presence
      of only one risk factor is still a matter of debate. Studies on the interaction
      between the two risk factors yielded conflicting data and no consensus has been
      reached in the last years. In addition, the interaction between H. pylori
      infection and low-dose ASA remains even more controversial. In real clinical
      practice, we can find different clinical scenarios involving these three factors
      associated with the presence of different gastrointestinal and cardiovascular
      risk factors. These huge variety of possible combinations greatly hinder the
      decision making process of physicians. 

PMID- 25071337
TI  - Osteoporosis and fractures in liver disease: relevance, pathogenesis and
      therapeutic implications.
AB  - It is being increasingly recognized that patients with liver disease develop bone
      loss that can be severe enough to lead to atraumatic fractures and thus markedly
      diminish life quality and expectancy. The estimated prevalence for liver-related
      osteoporosis is between 20-420/100000 of the general population, and fractures
      between 60-880/100000. It should be kept in mind that up to 40% of patients with
      chronic liver disease may experience a fracture. The pathogenic mediators include
      fibronectin, insulin like growth factor-I, and various cytokines, but decreased
      vitamin D and/or treatment with corticosteroids contribute to worsening bone
      health. Despite the advances in bone biology that have shed some light on the
      pathogenesis of this bone loss, treatment options remain nonspecific and tightly
      linked to treatments of other forms of osteoporosis. Thus, treatment should
      include calcium and vitamin D supplementation in all patients with chronic liver
      disease. Therapy with bisphosphonates should be considered, especially in
      patients receiving corticosteroids. This review focuses on the prevalence of this
      entity as well as the evidence available with regard to the pathogenesis of bone
      loss in liver disease, the diagnostic steps required in all patients, and the
      therapeutic options available. 

PMID- 25071339
TI  - Rapid on-site evaluation of endoscopic-ultrasound-guided fine-needle aspiration
      diagnosis of pancreatic masses.
AB  - Endoscopic ultrasound (EUS) has become an essential tool for the study of
      pancreatic diseases. Specifically, EUS plays a pivotal role evaluating patients
      with a known or suspected pancreatic mass. In this setting, differential
      diagnosis remains a clinical challenge. EUS-guided fine-needle aspiration (FNA)
      and fine-needle biopsy (FNB) have been proven to be safe and useful tools in this
      setting. EUS-guided FNA and FNB, by obtaining cytological and/or histological
      samples, are able to diagnose pancreatic lesions with high sensitivity and
      specificity. In this context, several methodological features, trying to increase
      the diagnostic yield of EUS-guided FNA and FNB, have been evaluated. In this
      review, we focus on the role of rapid on-site evaluation (ROSE). From data
      reported in the literature, ROSE may increase diagnostic yield of EUS-FNA
      specimens by 10%-30%, and thus, diagnostic accuracy. However, we should point out
      that many recent studies have reported adequacy rates of > 90% without ROSE,
      indicating that, perhaps, at high-volume centers, ROSE may not be indispensable
      to achieve excellent results. The use of ROSE can be considered important during
      the learning curve of EUS-FNA, and also in hospital with diagnostic accuracy
      rates < 90%. 

PMID- 25071340
TI  - Epidemiology, demographic characteristics and prognostic predictors of ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic disease characterized by diffuse
      inflammation of the mucosa of the colon and rectum. The hallmark clinical symptom
      of UC is bloody diarrhea. The clinical course is marked by exacerbations and
      remissions, which may occur spontaneously or in response to treatment changes or
      intercurrent illnesses. UC is most commonly diagnosed in late adolescence or
      early adulthood, but it can occur at any age. The incidence of UC has increased
      worldwide over recent decades, especially in developing nations. In contrast,
      during this period, therapeutic advances have improved the life expectancy of
      patients, and there has been a decrease in the mortality rate over time. It is
      important to emphasize that there is considerable variability in the phenotypic
      presentation of UC. Within this context, certain clinical and demographic
      characteristics are useful in identifying patients who tend to have more severe
      evolution of the disease and a poor prognosis. In this group of patients, better
      clinical surveillance and more intensive therapy may change the natural course of
      the disease. The aim of this article was to review the epidemiology and
      demographic characteristics of UC and the factors that may be associated with its
      clinical prognosis. 

PMID- 25071341
TI  - Ulcerative colitis as a polymicrobial infection characterized by sustained broken
      mucus barrier.
AB  - To reduce medication for patients with ulcerative colitis (UC), we need to
      establish the etiology of UC. The intestinal microbiota of patients with
      inflammatory bowel disease (IBD) has been shown to differ from that of healthy
      controls and abundant data indicate that it changes in both composition and
      localization. Small intestinal bacterial overgrowth is significantly higher in
      IBD patients compared with controls. Probiotics have been investigated for their
      capacity to reduce the severity of UC. The luminal surfaces of the
      gastrointestinal tract are covered by a mucus layer. This normally acts as a
      barrier that does not allow bacteria to reach the epithelial cells and thus
      limits the direct contact between the host and the bacteria. The mucus layer in
      the colon comprises an inner layer that is firmly adherent to the intestinal
      mucosa, and an outer layer that can be washed off with minimal rinsing. Some
      bacteria can dissolve the protective inner mucus layer. Defects in renewal and
      formation of the inner mucus layer allow bacteria to reach the epithelium and
      have implications for the causes of colitis. In this review, important elements
      of UC pathology are thought to be the intestinal bacteria, gut mucus, and the
      mucosa-associated immune system. 

PMID- 25071342
TI  - Establishment of an orthotopic pancreatic cancer mouse model: cells suspended and
      injected in Matrigel.
AB  - AIM: To establish an orthotopic mouse model of pancreatic cancer that mimics the
      pathological features of exocrine pancreatic adenocarcinoma. METHODS: Pan02 cells
      were suspended in low-temperature Matrigel and injected into the parenchyma of
      pancreatic tails of C57BL/6 mice, with cells suspended in phosphate buffered
      saline (PBS) serving as a control. Primary and implanted tumors were confirmed
      pathologically. The rate of tumor formation and intraperitoneal implantation in
      the two groups were compared at different time points after injection. Leakage
      and intra-abdominal dispersion of Matrigel and PBS, both dyed with methylene
      blue, were compared after injection into the parenchyma of the pancreas. We
      observed adherence and proliferation in Pan02 cells suspended in Matrigel in
      vitro. We also compared the pathological manifestation of this orthotopic
      pancreatic cancer model in the head and tails of the pancreas. The
      characteristics of the origin of epithelial cells and exocrine markers of
      established orthotopic pancreatic tumors were confirmed using
      immunohistochemistry. RESULTS: Diluted Matrigel could form a gel drip in the
      pancreatic parenchyma, effectively preventing leakage from the injection site and
      avoiding dispersion in the abdominal cavity. Pan02 cells were able to adhere to a
      dish, proliferate, and migrate in the gel drip. The tumor formation rate in the
      Matrigel group was 100% at both 2 and 3 wk after injection, whereas it was 25.0%
      and 37.5% in the PBS group at 2 and 3 wk, respectively (P < 0.05). The
      intraperitoneal tumor implantation rate was 75.0% in the PBS group after 3 wk of
      injection, while it was 12.5% in the Matrigel group (P < 0.05). Hepatoduodenal
      ligament and duodenal invasions with obstructive jaundice and upper digestive
      obstruction with mesenteric lymph node metastasis were observed in the pancreatic
      head group. In the pancreatic tail group, spleen and gastric invasion were
      dominant, leading to retroperitoneal lymph nodes metastasis. Positive
      immunohistochemical staining of cytokeratin and negative staining of vimentin and
      chromogranin A confirmed that the orthotopic pancreatic tumor injected with Pan02
      cells suspended in Matrigel was of epithelial origin and expressed exocrine
      markers of cancer. CONCLUSION: This method of low-temperature Matrigel suspension
      and injection is effective for establishing an orthotopic mouse model of
      pancreatic cancer.

PMID- 25071343
TI  - Viral infection parameters not nucleoside analogue itself correlates with host
      immunity in nucleoside analogue therapy for chronic hepatitis B.
AB  - AIM: To determine the relationship between host immunity and the characteristics
      of viral infection or nucleoside analogues (NAs) themselves in patients with
      chronic hepatitis B (CHB) receiving NA therapy. METHODS: Fifty-two hepatitis B
      envelope antigen (HBeAg) positive CHB patients were enrolled and divided equally
      into two groups. One group received telbivudine (LDT, 600 mg/d), and the other
      group received lamivudine (LAM, 100 mg/d). Clinical, virological and
      immunological parameters were assessed at the baseline and at 4, 12, 24, 36 and
      48 wk. RESULTS: Both groups achieved significant hepatitis B virus (HBV)
      replication inhibition and alanine aminotransferase normalization at 48 wk. At
      the baseline, compared to healthy controls, CHB patients had a lower circulating
      CD8 T cell frequency (29.44% +/- 11.55% vs 37.17% +/- 7.30%, P = 0.03) and higher
      frequencies of programmed death 1 positive CD8 T cells (PD-1+ CD8 T) (16.48% +/-
      10.82% vs 7.02% +/- 3.62%, P = 0.0001) and CD4+ CD25+ FoxP3+ T regulatory cells
      (Tregs) (23.64% +/- 9.38% vs 13.60% +/- 6.06%, P = 0.001). On therapy, at the
      beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid (HBV
      DNA) and HBeAg declining, the frequencies of PD-1+ CD8 T cells and Treg cells
      gradually and significantly declined at 12 and 24 wk in both therapy groups. At
      treatment week 4, patients treated with LDT had a lower frequency of PD-1+ CD8 T
      cells compared to patients treated with LAM (10.08% +/- 6.83% vs 20.51% +/-
      20.96%, P = 0.02). The frequency of PD-1+ CD8 T cells in all of the CHB patients
      was significantly correlated with both the HBV DNA level (r = 0.45, P = 0.01) and
      HBeAg level (r = 0.47, P = 0.01) at treatment week 24, but the frequency of Treg
      cells was only significantly correlated with the HBeAg level (r = 0.44,P = 0.02).
      Furthermore, the ability of CD8 T cells to secrete pro-inflammatory cytokines was
      partially restored after 24 wk of therapy. CONCLUSION: NA-mediated HBV
      suppression could down-regulate the production of negative regulators of host
      immunity during the first 24 wk of therapy and could partially restore the
      ability of CD8 T cells to secrete pro-inflammatory cytokines. This immune
      modulating response may be correlated with the levels of both HBV DNA and HBeAg.

PMID- 25071344
TI  - Down-regulation of FoxM1 inhibits viability and invasion of gallbladder carcinoma
      cells, partially dependent on inducement of cellular senescence.
AB  - AIM: To investigate the effect of knockdown of Forkhead box M1 (FoxM1) on the
      proliferation and invasion capacities of human gallbladder carcinoma (GBC)-SD
      cells. METHODS: Four FoxM1 shRNAs were transfected into GBC-SD cells with
      Lipofectamine 2000 to select the appropriate shRNA for down-regulation of FoxM1.
      A recombinant lentivirus for shFoxM1 (Lv-shFoxM1), which expresses FoxM1-specific
      shRNA, and a negative control carrying green fluorescent protein, which expresses
      a scrambled RNA, were constructed. After transfection with the recombinant
      adenovirus and screened with puromycin, RT-PCR and Western blot were utilized to
      evaluate the inhibition efficiency. Cell viability was evaluated by MTT assay,
      and cell migration and invasion were assessed using the Transwell system. Cells
      were suspended in serum-free medium and seeded into Transwell inserts either
      uncoated (for migration assay) or coated (for invasion assay) with growth factor
      reduced Matrigel. To verify the involvement of FoxM1 in the senescence of tumor
      cells, staining of senescence beta-galactosidase (SA beta-gal), the widely used
      biomarker of cellular senescence, was also performed. RESULTS: After successful
      transfection of four FoxM1 small interfering RNAs (shRNAs) with Lipofectamine
      2000, the shF1822 was selected as the most appropriate shRNA according to its
      obvious inhibitory effect. The recombinant adenovirus was then constructed with
      the shF1822 and successfully transfected into the GBC-SD cells, resulting in the
      significant inhibition of FoxM1 expression at both the mRNA and protein levels,
      compared with the negative control (P < 0.05). After transfection, down
      regulation of FoxM1 significantly inhibited cell viability according to the MTT
      assay (P < 0.05). In addition, Transwell migration and invasion assays also
      suggested the suppression of invasion ability of the transfected cells. SA beta
      gal staining showed that down-regulation of FoxM1 could induce more senescent GBC
      cells (P < 0.05), suggesting the possible involvement of the senescence process
      of the FoxM1-deficient cells in GBC. CONCLUSION: FoxM1 is functionally involved
      in viability of GBC cells, partially dependent on the inducement of cellular
      senescence, and is a potential target for GBC therapy.

PMID- 25071345
TI  - Conventional, but not remote ischemic preconditioning, reduces iNOS transcription
      in liver ischemia/reperfusion.
AB  - AIM: To study the effects of preconditioning on inducible nitric oxide synthase
      (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver
      ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized
      into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic
      preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R
      IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10
      min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was
      analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously
      sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx
      levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS
      mRNA was significantly higher in the R-IPC (DeltaCt: 3.44 +/- 0.57) group than in
      the IPC (DeltaCt: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor
      transcription activity was reduced in the IPC group (DeltaCt: 1.88 +/- 0.53 to
      4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In
      the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3
      +/- 2.2 to 4.7 +/- 1.2 MUmol/L) at the end of ischemia compared with the levels
      in early ischemia (P = 0.008). A similar trend was observed in the IPC group
      (11.8 +/- 2.1 to 6.4 +/- 1.5 MUmol/L), although this difference was not
      statistically significant. The levels of NOx rose quickly during reperfusion in
      both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor
      transcription during early reperfusion, indicating a lower inflammatory reaction.
      NOx is consumed in the ischemic liver lobe.

PMID- 25071346
TI  - Association of caveolin-3 and cholecystokinin A receptor with cholesterol
      gallstone disease in mice.
AB  - AIM: To investigate the role of caveolin-3 (CAV3) and cholecystokinin A receptor
      (CCKAR) in cholesterol gallstone disease (CGD). METHODS: To establish a mouse
      model of CGD, male C57BL/6 mice were fed with a lithogenic diet containing 1.0%
      cholic acid, 1.25% cholesterol and 15% fat; a similar control group was given a
      normal diet. The fresh liver weights and liver-to-body weight ratio were compared
      between the two groups after one month. Serum lipid profile and bile composition
      were determined with an autoanalyzer. The Cav3 and Cckar mRNA and CAV3 and CCKAR
      protein levels in the liver and gallbladder were determined via real-time
      polymerase chain reaction and Western blot, respectively. RESULTS: Establishment
      of the mouse CGD model was verified by the presence of cholesterol gallstones in
      mice fed the lithogenic diet. Compared with mice maintained on a normal diet,
      those fed the lithogenic diet had significantly higher mean liver-to-body weight
      ratio (0.067 +/- 0.007 vs 0.039 +/- 0.007, P < 0.01), serum total cholesterol
      (4.22 +/- 0.46 mmol/L vs 2.21 +/- 0.11 mmol/L, P < 0.001), bile total cholesterol
      (1.33 +/- 0.33 mmol/L vs 0.21 +/- 0.11 mmol/L, P < 0.001), and bile phospholipid
      concentrations (3.55 +/- 1.40 mmol/L vs 1.55 +/- 0.63 mmol/L, P = 0.04), but
      lower total bile acid concentrations (726.48 +/- 51.83 MUmol/L vs 839.83 +/-
      23.74 MUmol/L, P = 0.007). The lithogenic diet was also associated with
      significantly lower CAV3 in the liver and lower CAV3 and CCKAR in the gallbladder
      compared with the control mice (all P < 0.05). CONCLUSION: CAV3 and CCKAR may be
      involved in cholesterol gallstone disease.

PMID- 25071347
TI  - Remote ischemic postconditioning protects against gastric mucosal lesions in
      rats.
AB  - AIM: To investigate the protective effects of remote ischemic postconditioning
      (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury.
      METHODS: Gastric IR was established in male Wistar rats by placing an elastic
      rubber band under a pressure of 290-310 mmHg on the proximal part of both lower
      limbs for 3 h followed by reperfusion for 0, 1, 3, 6, 12 or 24 h. RIP was
      performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of
      the femoral aortic immediately after IR and before reperfusion for up to 24 h.
      Rats were randomly assigned to receive IR (n = 36), IR followed by RIP (n = 36),
      or sham treatment (n = 36). Gastric tissue samples were collected from six
      animals in each group at each timepoint and processed to determine levels of
      malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD) and
      myeloperoxidase (MPO). Additional samples were processed for histologic analysis
      by hematoxylin and eosin staining. Blood samples were similarly collected to
      determine serum levels of lactate dehydrogenase (LDH), creatine kinase (CK),
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-10. RESULTS: The
      pathologic changes in gastric tissue induced by IR were observed by light
      microscopy. Administration of RIP dramatically reduced the gastric damage score
      after 6 h of reperfusion (5.85 +/- 0.22 vs 7.72 +/- 0.43; P < 0.01). In addition,
      RIP treatment decreased the serum activities of LDH (3.31 +/- 0.32 vs 6.46 +/-
      0.03; P < 0.01), CK (1.94 +/- 0.20 vs 4.54 +/- 0.19; P < 0.01) and the
      concentration of TNF-alpha (53.82 +/- 0.85 vs 88.50 +/- 3.08; P < 0.01), and
      elevated the concentration of IL-10 (101.46 +/- 5.08 vs 99.77 +/- 4.32; P < 0.01)
      induced by IR at 6 h. Furthermore, RIP treatment prevented the marked elevation
      in MDA (3.79 +/- 0.29 vs 6.39 +/- 0.81) content, XOD (7.81 +/- 0.75 vs 10.37 +/-
      2.47) and MPO (0.47 +/- 0.05 vs 0.82 +/- 0.03) activities, and decrease in SOD
      (4.95 +/- 0.32 vs 3.41 +/- 0.38; P < 0.01) activity in the gastric tissue as
      measured at 6 h. CONCLUSION: RIP provides effective functional protection and
      prevents cell injury to gastric tissue induced by limb IR via anti-inflammatory
      and antioxidant actions.

PMID- 25071348
TI  - Liver fibrosis evaluation by ARFI and APRI in chronic hepatitis C.
AB  - AIM: To explore the value of liver fibrosis assessment by acoustic radiation
      force impulse (ARFI) and the AST/PLT ratio index (APRI) in chronic hepatitis C
      patients. METHODS: One hundred and twenty eight patients with chronic hepatitis C
      were examined using ARFI elastometry and APRI, calculated according to known
      formulae. The gold standard of liver biopsy was referred; ROC curve analysis was
      used to assess all ARFI and APRI values. The corresponding cut-off values,
      sensitivities, and specificities were calculated and compared. In addition, the
      correlation of liver fibrosis stages in chronic hepatitis C patients with ARFI
      measurements and APRI were also tested to evaluate significant data. RESULTS: The
      values of ARFI in S1-S4 were 1.23 +/- 0.34 m/s, 1.48 +/- 0.43 m/s, 2.06 +/- 0.45
      m/s, and 2.30 +/- 0.87 m/s. The values of APRI in S1-S4 were 0.31 +/- 0.45 m/s,
      0.28 +/- 0.38 m/s, 0.58 +/- 0.59 m/s and 0.65 +/- 0.34 m/s. ARFI (r = 0.649, P <
      0.05) showed a better correlation with liver fibrosis stages in chronic hepatitis
      C than APRI (r = 0.478, P < 0.05). The areas under the ROC curves for ARFI and
      APRI were 0.775 and 0.721 for stages >= S2, 0.901 and 0.787 for stages >= S3, and
      0.792 and 0.780 for S = 4, respectively. CONCLUSION: Both ARFI and APRI could
      evaluate liver fibrosis stages in chronic hepatitis C. ARFI is more accurate than
      the APRI index.

PMID- 25071349
TI  - Postprandial response of bone turnover markers in patients with Crohn's disease.
AB  - AIM: To investigate the postprandial response of bone turnover markers in
      patients with Crohn's disease (CD). METHODS: Fifty nine patients with CD aged 38
      +/- 14 years, and 45 healthy individuals matched for age and body mass index were
      included in the study. All participants underwent an oral glucose tolerance test
      (OGTT) after an overnight fast and serum levels of the bone resorption marker C
      terminal crosslinking telopeptide of type I collagen (CTX-I) and the bone
      formation marker procollagen type I N propeptide were measured. Activity of the
      disease was assessed by calculation of the Crohn's disease activity index (CDAI).
      RESULTS: Serum CTX-I was significantly higher in patients compared to controls
      (CTX-I: 453 +/- 21 pg/mL vs 365 +/- 25 pg/mL, P = 0.008), and values were
      significantly correlated with the activity of the disease (r = 0.435, P = 0.001).
      Results from OGTT-induced suppression of CTX-I showed two different trends.
      Patients with more active disease (assessed as CDAI > 150) had a more excessive
      suppression of CTX-I compared to controls (55% vs 43% P < 0.001), while patients
      on remission (assessed as CDAI < 150) demonstrated an attenuated CTX-I
      suppression (30% vs 43% P < 0.001). In line with this, CTX-I suppression after
      oral glucose load was significantly correlated with the activity of the disease
      (r = 0.913, P < 0.001). CONCLUSION: The physiological skeletal response of
      postprandial suppression of bone resorption is maintained in patients with CD and
      is strongly dependent to the activity of the disease.

PMID- 25071350
TI  - Association of metabolic syndromes and risk factors with ampullary tumors
      development: a case-control study in China.
AB  - AIM: To evaluate the risk factors for ampullary adenoma and ampullary cancer.
      METHODS: This case-control study included ampullary tumor patients referred to
      Peking Union Medical College Hospital. Controls were randomly selected from an
      existing database of healthy individuals at the Health Screening Center of the
      same hospital. Data on metabolic syndromes, medical conditions, and family
      history were collected by retrospective review of the patients' records and
      health examination reports, or by interview. RESULTS: A total of 181 patients and
      905 age- and sex-matched controls were enrolled. We found that a history of
      diabetes, cholecystolithiasis, low-density lipoprotein, and apolipoprotein A were
      significantly related to ampullary adenomas. Diabetes, cholecystolithiasis,
      chronic pancreatitis, total cholesterol, high-density lipoprotein, and
      apolipoprotein A were also significantly related to ampullary cancer. CONCLUSION:
      Some metabolic syndrome components and medical conditions are potential risk
      factors for the development of ampullary tumors. Cholelithiasis, diabetes, and
      apolipoprotein A may contribute to the malignant transformation of benign
      ampullary adenomas into ampullary cancer.

PMID- 25071351
TI  - Esophageal dilations in eosinophilic esophagitis: a single center experience.
AB  - AIM: To diagnose the clinical and histologic features that may be associated with
      or predictive of the need for dilation and dilation related complications;
      examine the safety of dilation in patients with eosinophilic esophagitis (EoE).
      METHODS: The medical records of all patients diagnosed with EoE between January
      2002 and July 2010 were retrospectively reviewed. Esophageal biopsies were
      reexamined by an experienced pathologist to confirm the diagnosis (>= 15 eos/hpf
      per current guidelines). Patients were divided into 2 groups: patients who did
      not receive dilation therapy and those who did. Demographics, clinical history,
      the use of pharmacologic therapy, endoscopic and pathology findings, and the
      number of biopsies and dilations carried out, if any, and their locations were
      recorded for each patient. The dilation group was further examined based on the
      interval between diagnosis and dilation, and whether or not a complication
      occurred. RESULTS: Sixty-one patients were identified with EoE and 22 (36%) of
      them underwent esophageal dilations for stricture/narrowing. The peak eos/hpf was
      significantly higher in patients who received a dilation (P = 0.04). Four (18% of
      pts.) minor complications occurred: deep mucosal tear 1, and small mucosal tears
      3. There were no cases of esophageal perforations. Higher peak eos/hpf counts
      were not associated with increased risk of complications. CONCLUSION: Esophageal
      dilation appears to be a safe procedure in EoE patients, carrying a low
      complication rate. No correlation was found between the peak of eosinophil count
      and complication rate. Complications can occur independently of the histologic
      features. The long-term outcome of EoE treatment, with or without dilation, needs
      to be determined.

PMID- 25071352
TI  - Treatment of rectal cancer by transanal endoscopic microsurgery: experience with
      425 patients.
AB  - AIM: To describe our experience in treating rectal cancer by transanal endoscopic
      microsurgery (TEM), report morbidity and mortality and oncological outcome.
      METHODS: A total of 425 patients with rectal cancer (120 T1, 185 T2, 120 T3
      lesions) were staged by digital rectal examination, rectoscopy, transanal
      endosonography, magnetic resonance imaging and/or computed tomography. Patients
      with T1-N0 lesions and favourable histological features underwent TEM
      immediately. Patients with preoperative stage T2-T3-N0 underwent preoperative
      high-dose radiotherapy; from 1997 those aged less than 70 years and in good
      general health also underwent preoperative chemotherapy. Patients with T2-T3-N0
      lesions were restaged 30 d after radiotherapy and were then operated on 40-50 d
      after neoadjuvant therapy. The instrumentation designed by Buess was used for all
      procedures. RESULTS: There were neither perioperative mortality nor
      intraoperative complications. Conversion to other surgical procedures was never
      required. Major complications (urethral lesions, perianal or retroperitoneal
      phlegmon and rectovaginal fistula) occurred in six (1.4%) patients and minor
      complications (partial suture line dehiscence, stool incontinence and rectal
      haemorrhage) in 42 (9.9%). Postoperative pain was minimal. Definitive
      histological examination of the 425 malignant lesions showed 80 (18.8%) pT0, 153
      (36%) pT1, 151 (35.5%) pT2, and 41 (9.6%) pT3 lesions. Eighteen (4.2%) patients
      (ten pT2 and eight pT3) had a local recurrence and 16 (3.8%) had distant
      metastasis. Cancer-specific survival rates at the end of follow-up were 100% for
      pT1 patients (253 mo), 93% for pT2 patients (255 mo) and 89% for pT3 patients
      (239 mo). CONCLUSION: TEM is a safe and effective procedure to treat rectal
      cancer in selected patients without evidence of nodal involvement. T2-T3 lesions
      require preoperative neoadjuvant therapy.

PMID- 25071353
TI  - Prognostic significance of nuclear hepatoma-derived growth factor expression in
      gallbladder cancer.
AB  - AIM: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in
      benign and malignant gallbladder lesions and to determine its clinicopathological
      significance. METHODS: We studied 40 patients with gallbladder cancer (GBC) and a
      control group of 40 patients with cholelithiasis. All diagnoses of GBC and
      cholelithiasis were confirmed by histopathological examination after surgery.
      None of the patients received chemotherapy or radiotherapy before surgery. All
      tissue samples were fixed in 4% formalin immediately after removal and embedded
      in paraffin for immunohistochemical staining. The HDGF expression in the GBC and
      cholelithiasis specimens was examined by immunohistochemical staining. The
      relationship between the HDGF expression and the clinicopathological parameters
      of GBC was analyzed. RESULTS: Nuclear HDGF expression was significantly higher
      (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear
      HDGF levels were associated with histopathological subtype (P < 0.05), clinical
      stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age,
      history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier
      analysis showed that positive nuclear HDGF expression was associated with
      decreased overall survival (P < 0.01). Multivariate Cox regression analysis
      showed that nuclear HDGF expression and lymph node metastasis were independent
      risk factors for disease-free survival. CONCLUSION: The expression of nuclear
      HDGF might be closely related to the carcinogenesis, clinical biological
      behaviors, and prognosis of gallbladder adenocarcinoma.

PMID- 25071354
TI  - Safety trial of high-intensity focused ultrasound therapy for pancreatic cancer.
AB  - AIM: To evaluate the safety and clinical application of high-intensity focused
      ultrasound (HIFU) therapy for unresectable pancreatic cancer (PC). METHODS:
      Thirty PC patients (16 cases in stage III and 14 cases in stage IV) with
      visualized pancreatic tumors were admitted for HIFU therapy as an optional local
      therapy in addition to systemic chemotherapy or chemoradiotherapy. Informed
      consent was obtained. This study began at the end of 2008 and was approved by the
      ethics committee of our hospital [Institutional Review Board (IRB): 890]. The
      HIFU device used was the FEP-BY02 (Yuande Bio-Medical Engineering, Beijing,
      China). RESULTS: The mean tumor size after HIFU therapy changed to 30.9 +/- 1.7
      mm from 31.7 +/- 1.7 mm at pre-therapy. There were no significant changes in
      tumor size, mean number of treatment sessions (2.7 +/- 0.1 mm), or mean total
      treatment time (2.4 +/- 0.1 h). The rate of symptom relief effect was 66.7%. The
      effectiveness of primary lesion treatment was as follows: complete response, 0;
      partial response, 4; stable disease, 22; progressive disease, 4. Treatment after
      HIFU therapy included 2 operations, 24 chemotherapy treatments, and 4 best
      supportive care treatments. Adverse events occurred in 10% of cases, namely
      pseudocyst formation in 2 cases and mild pancreatitis development in 1. However,
      no severe adverse events occurred in this study. CONCLUSION: We suggest that HIFU
      therapy is safe and has the potential to be a new method of combination therapy
      for PC.

PMID- 25071355
TI  - Study of detection times for liver stiffness evaluation by shear wave
      elastography.
AB  - AIM: To investigate enough valid measurements (VMs) to assess liver fibrosis in
      chronic hepatitis B patients (CHB). METHODS: One hundred and twelve CHB patients
      (25 women, 87 men) with a mean age of 38.43 years received liver stiffness
      evaluations using real-time shear wave elastography for 10 VMs. All patients
      underwent liver biopsy. Based on the biopsy pathology, the liver stiffness data
      obtained from different VMs (1, 2, 3, 5 and 10 times) were compared for the
      evaluation of liver fibrosis. The correlation between the elastic modulus means
      of the liver obtained from different VMs of detection at each pathological stage
      was analysed. The receiver operating characteristic (ROC) curve was employed to
      determine the diagnostic performance of different VMs of detection, and the areas
      under the ROC curve of different groups were compared. RESULTS: The liver
      stiffness values obtained from 1 VM, 2 VMs, 3 VMs, 5 VMs and all 10 VMs for stage
      F0 were 6.95 +/- 2.01 kPa, 6.87 +/- 1.83 kPa, 6.90 +/- 1.88 kPa, 6.95 +/- 1.93
      kPa and 7.15 +/- 1.89 kPa, respectively (F = 0.043, P = 0.996). For stage F1,
      these values were 7.12 +/- 1.72 kPa, 7.24 +/- 1.72 kPa, 7.21 +/- 1.74 kPa, 7.10
      +/- 1.78 kPa and 7.04 +/- 1.70 kPa, respectively (F = 0.075, P = 0.990). For
      stage F2, they were 9.37 +/- 3.87 kPa, 9.18 +/- 3.68 kPa, 9.19 +/- 3.81 kPa, 9.18
      +/- 3.81 kPa and 9.19 +/- 3.53 kPa, respectively (F = 0.012, P = 1.000). For
      stage F3, these were 11.91 +/- 3.88 kPa, 11.78 +/- 4.04 kPa, 11.83 +/- 4.07 kPa,
      11.94 +/- 4.17 kPa and 12.00 +/- 4.02 kPa, respectively (F = 0.010, P = 1.000).
      For stage F4, the readings were 19.30 +/- 7.63 kPa, 19.40 +/- 7.36 kPa, 19.54 +/-
      7.43 kPa, 19.73 +/- 7.21 kPa and 20.25 +/- 7.22 kPa, respectively (F = 0.054, P =
      0.995). There were no significant differences between these groups. Intraclass
      correlation coefficients among different pathological stages (F0-F4) with
      different detection VMs were 0.995, 0.993, 0.996, 0.994 and 0.996, respectively.
      The mean elasticity values from 1 VM, 2 VMs, 3 VMs, 5 VMs and 10 VMs can
      accurately distinguish fibrosis stages (F0 vs F1234, F01 vs F234, F012 vs F34 and
      F0123 vs F4) with no significant differences in the five groups (P > 0.05 for
      all). CONCLUSION: One VM may be sufficient to assess liver fibrosis by using SWE
      without any significant loss of accuracy in patients with CHB. However, future
      studies of larger patient samples are necessary for the validation of this
      method.

PMID- 25071356
TI  - Alterations in enterocyte mitochondrial respiratory function and enzyme
      activities in gastrointestinal dysfunction following brain injury.
AB  - AIM: To determine the alterations in rat enterocyte mitochondrial respiratory
      function and enzyme activities following traumatic brain injury (TBI). METHODS:
      Fifty-six male SD rats were randomly divided into seven groups (8 rats in each
      group): a control group (rats with sham operation) and traumatic brain injury
      groups at 6, 12, 24 h, days 2, 3, and 7 after operation. TBI models were induced
      by Feendy's free-falling method. Mitochondrial respiratory function (respiratory
      control ratio and ADP/O ratio) was measured with a Clark oxygen electrode. The
      activities of respiratory chain complex I-IV and related enzymes were determined
      by spectrophotometry. RESULTS: Compared with the control group, the mitochondrial
      respiratory control ratio (RCR) declined at 6 h and remained at a low level until
      day 7 after TBI (control, 5.42 +/- 0.46; 6 h, 5.20 +/- 0.18; 12 h, 4.55 +/- 0.35;
      24 h, 3.75 +/- 0.22; 2 d, 4.12 +/- 0.53; 3 d, 3.45 +/- 0.41; 7 d, 5.23 +/- 0.24,
      P < 0.01). The value of phosphate-to-oxygen (P/O) significantly decreased at 12,
      24 h, day 2 and day 3, respectively (12 h, 3.30 +/- 0.10; 24 h, 2.61 +/- 0.21; 2
      d, 2.95 +/- 0.18; 3 d, 2.76 +/- 0.09, P < 0.01) compared with the control group
      (3.46 +/- 0.12). Two troughs of mitochondrial respiratory function were seen at
      24 h and day 3 after TBI. The activities of mitochondrial complex I (6 h: 110 +/-
      10, 12 h: 115 +/- 12, 24 h: 85 +/- 9, day 2: 80 +/- 15, day 3: 65 +/- 16, P <
      0.01) and complex II (6 h: 105 +/- 8, 12 h: 110 +/- 92, 24 h: 80 +/- 10, day 2:
      76 +/- 8, day 3: 68 +/- 12, P < 0.01) were increased at 6 h and 12 h following
      TBI, and then significantly decreased at 24 h, day 2 and day 3, respectively.
      However, there were no differences in complex I and II activities between the
      control and TBI groups. Furthermore, pyruvate dehydrogenase (PDH) activity was
      significantly decreased at 6 h and continued up to 7 d after TBI compared with
      the control group (6 h: 90 +/- 8, 12 h: 85 +/- 10, 24 h: 65 +/- 12, day 2: 60 +/-
      9, day 3: 55 +/- 6, day 7: 88 +/- 11, P < 0.01). The changes in alpha
      ketoglutaric dehydrogenase (KGDH) activity were similar to PDH, except that the
      decrease in KGDH activity began at 12 h after TBI (12 h: 90 +/- 12, 24 h: 80 +/-
      9, day 2: 76 +/- 15, day 3: 68 +/- 7, day 7: 90 +/- 13, P < 0.01). No significant
      change in malate dehydrogenase (MDH) activity was observed. CONCLUSION: Rat
      enterocyte mitochondrial respiratory function and enzyme activities are inhibited
      following TBI. Mitochondrial dysfunction may play an important role in TBI
      induced gastrointestinal dysfunction.

PMID- 25071357
TI  - Atrial fibrillation in patients with gastroesophageal reflux disease: a
      comprehensive review.
AB  - AIM: To analyze the potential relationship between gastroesophageal reflux
      disease (GERD) and the development of atrial fibrillation (AF). METHODS: Using
      the key words "atrial fibrillation and gastroesophageal reflux", "atrial
      fibrillation and esophagitis, peptic", "atrial fibrillation and hernia, hiatal"
      the PubMed, EMBASE, Cochrane Library, OVIDSP, WILEY databases were screened for
      relevant publications on GERD and AF in adults between January 1972-December
      2013. Studies written in languages other than English or French, studies not
      performed in humans, reviews, case reports, abstracts, conference presentations,
      letters to the editor, editorials, comments and opinions were not taken into
      consideration. Articles treating the subject of radiofrequency ablation of AF and
      the consecutive development of GERD were also excluded. RESULTS: Two thousand one
      hundred sixty-one titles were found of which 8 articles met the inclusion
      criteria. The presence of AF in patients with GERD was reported to be between
      0.62%-14%, higher compared to those without GERD. Epidemiological data provided
      by these observational studies showed that patients with GERD, especially those
      with more severe GERD-related symptoms, had an increased risk of developing AF
      compared with those without GERD, but a causal relationship between GERD and AF
      could not be established based on these studies. The mechanisms of AF as a
      consequence of GERD remain largely unknown, with inflammation and vagal
      stimulation playing a possible role in the development of these disorders.
      Treatment with proton pomp inhibitors may improve symptoms related to AF and
      facilitate conversion to sinus rhythm. CONCLUSION: Although links between AF and
      GERD exist, large randomized clinical studies are required for a better
      understanding of the relationship between these two entities.

PMID- 25071358
TI  - Gene-diet interactions in gastric cancer risk: a systematic review.
AB  - AIM: To conduct a systematic review of the published epidemiological studies
      investigating the association of the interactions between gene variants and
      dietary intake with gastric cancer risk. METHODS: A literature search was
      conducted in PubMed, EMBASE, and MEDLINE for articles published between January
      2000 and July 2013, and 38 studies were identified. Previous studies included
      various dietary factors (e.g., fruits and vegetables, soybean products, salt,
      meat, and alcohol) and genetic variants that are involved in various metabolic
      pathways. RESULTS: Studies suggest that individuals who carry high-risk genetic
      variants and demonstrate particular dietary habits may have an increased risk of
      gastric cancer compared with those who do not carry high-risk genetic variants.
      Distinctive dietary patterns and variations in the frequency of genetic variants
      may explain the higher incidence of gastric cancer in a particular region.
      However, most previous studies have limitations, such as a small sample size and
      a retrospective case-control design. In addition, past studies have been unable
      to elucidate the specific mechanism in gene-diet interaction associated with
      gastric carcinogenesis. CONCLUSION: Additional large prospective epidemiological
      and experimental studies are required to identify the gene-diet metabolic
      pathways related to gastric cancer susceptibility.

PMID- 25071359
TI  - Lifetime risk of esophageal adenocarcinoma in patients with Barrett's esophagus.
AB  - AIM: To investigate the lifetime risk of development of esophageal adenocarcinoma
      and/or high-grade dysplasia in patients diagnosed with Barrett's esophagus.
      METHODS: Data were extracted from the United Kingdom National Barrett's
      Oesophagus Registry on date of diagnosis, patient age and gender of 7877 patients
      from who had been registered from 35 United Kingdom centers. Life expectancy was
      evaluated from United Kingdom National Statistics data based upon gender and age
      at year at diagnosis. These data were then used with published estimates of
      annual adenocarcinoma and high-grade dysplasia incidences from meta-analyses and
      large population-based studies to estimate overall lifetime risk of development
      of these study endpoints. RESULTS: The mean age at diagnosis of Barrett's
      esophagus was 61.6 years in males and 67.3 years in females. The mean life
      expectancy at diagnosis was 23.1 years in males, 20.7 years in females and 22.2
      years overall. Using data from published meta-analyses, the lifetime risk of
      development of adenocarcinoma was between 1 in 8 and 1 in 14 and the lifetime
      risk of high-grade dysplasia or adenocarcinoma was 1 in 5 to 1 in 6. Using data
      from 3 large recent population-based cohort studies the lifetime risk of
      adenocarcinoma was between 1 in 10 and 1 in 37 and of the combined end-point of
      high-grade dysplasia and adenocarcinoma was between 1 in 8 and 1 in 20. Age at
      Barrett's esophagus diagnosis is reducing and life expectancy is increasing,
      which will partially counter-balance lower annual cancer incidence. CONCLUSION:
      There is a significant lifetime risk of development of high-grade dysplasia and
      adenocarcinoma in Barrett's esophagus.

PMID- 25071360
TI  - Severe splenic rupture after colorectal endoscopic submucosal dissection.
AB  - Splenic rupture (SR) after colonoscopy is a very rare but potentially serious
      complication. Delayed diagnosis is common, and may increase morbidity and
      mortality associated. There is no clear relation between SR and difficult
      diagnostic or therapeutic procedures, but it has been suggested that loop
      formation and excessive torquing might be risk factors. This is a case of a 65
      year-old woman who underwent endoscopic submucosal dissection (ESD) for lateral
      spreading tumor in the descending colon, and 36 h afterwards presented symptoms
      and signs of severe hypotension due to SR. Standard splenectomy was completed and
      the patient recovered uneventfully. Colorectal ESD is usually a long and position
      demanding technique, implying torquing and loop formation. To our knowledge this
      is the first case of SR after colorectal ESD reported in the literature.
      Endoscopists performing colorectal ESD in the left colon must be aware of this
      potential complication. 

PMID- 25071361
TI  - Undiagnosed Borrmann type II gastric cancer due to necrosis and regenerative
      epithelium.
AB  - Endoscopic biopsy is essential to the proper diagnosis and treatment of gastric
      cancer. Unfortunately, the results of endoscopic biopsy are not always the same
      as what is expected based on gross endoscopic findings. The results of endoscopic
      biopsy can be negative for malignancy in Borrmann type IV advanced gastric cancer
      (AGCa) or gastric lymphoma. However, in the case of type II AGCa, repeated
      biopsies negative for malignancy have not been reported. A 49-year-old male
      patient underwent esophagogastroduodenoscopy three times due to large gastric
      ulcer suspected to be Borrmann type II cancer. However, three repeat endoscopic
      biopsies with multiple specimens showed necrosis and superficial regenerative
      epithelium without malignant findings. The patient underwent laparoscopic distal
      gastrectomy with D2 lymph node dissection. The surgical specimen revealed that
      the mucosal layer was completely replaced with regenerative epithelium without
      cancer cells. 

PMID- 25071363
TI  - Neutrophil-lymphocyte ratio is useful for the prognosis of patients with
      hepatocellular carcinoma.
AB  - There is increasing evidence that neutrophil-lymphocyte ratio (NLR) may play a
      role in predicting recurrence in patients with hepatitis B virus-related
      hepatocellular carcinoma (HCC) after liver transplantation. In the original study
      by Yan et al, it was aimed to determine whether an elevated NLR is associated
      with tumor recurrence. Total tumor size (> 9 cm) and macro-vascular invasion were
      found to be more significant than NLR according to the multivariate logistic
      regression analysis. Therefore, substantive significance should be emphasized
      rather than NLR because total tumor size and macro-vascular invasion are easier
      and more expressive than NLR in assessing HCC recurrence. NLR and platelet
      lymphocyte ratio (PLR) are markers which are easy to obtain and can be used as
      inflammation indicators. Moreover, assessment of both NLR and PLR may add some
      value as a good predictor of risk for post-liver transplantation HCC recurrence.
      However, while the study was constructed on whole blood analysis, further details
      about the features and performance characteristics of the whole-blood analyzer,
      and preanalytical/analytical variables should also be mentioned. 

PMID- 25071362
TI  - Primary colonic melanoma presenting as ileocecal intussusception: case report and
      literature review.
AB  - Primary malignant melanoma originating in the colon is an extremely rare disease.
      Herein, we report a case of primary melanoma of the ascending colon. The patient
      was a 57-year-old male who was admitted to our hospital for persistent abdominal
      pain and episodes of bloody stool, nausea and vomiting. A computed tomography
      scan revealed lower intestinal intussusception and enlarged lymph nodes in the
      abdominal cavity and retroperitoneum. During laparoscopic operation, multiple
      enlarged lymph nodes were found. Several segments of the proximal small intestine
      were incarcerated into the distal small intestine, forming an internal hernia and
      obstruction. The necrotic terminal ileum was invaginated into the ascending
      cecum. Subsequently, adhesive internal hernia reduction and palliative right
      hemicolectomy were performed. Pathologic examination of the excised specimen
      revealed a polypoid mass in the ascending colon. Histological examination showed
      epithelioid and spindle tumor cells with obvious cytoplasmic melanin deposition.
      Immunohistochemical staining revealed that the tumor cells were positive for S
      100, HMB-45 and vimentin, confirming the diagnosis of melanoma. The patient
      history and a thorough postoperative investigation excluded the preexistence or
      coexistence of a primary lesion elsewhere in the skin, anus or oculus or at other
      sites. Thus, we consider our case to represent an aggressive primary colon
      melanoma presenting as ileocecal intussusception and intestinal obstruction. 

PMID- 25071364
TI  - Diagnostic PCR can be used to illuminate meiofaunal diets and trophic
      relationships.
AB  - Analysis of the meiofaunal food web is hampered because few prey have features
      that persist long enough in a predator's digestive tract to allow identification
      to species. Hence, at least for platyhelminth predators, direct observations of
      prey preference are almost nonexistent, and where they occur, prey identification
      is often limited to phylum. Studies using an in vitro approach are rare because
      they are extremely time-consuming and are subject to the criticism that predators
      removed from their natural environment may exhibit altered behaviors. Although
      PCR-based approaches have achieved wide application in food-web analysis, their
      application to meiofaunal flatworms suffers from a number of limitations. Most
      importantly, the microscopic size of both the predator and prey does not allow
      for removal of prey material from the digestive tract of the predator, and thus
      the challenge is to amplify prey sequences in the presence of large quantities of
      predator sequence. Here, we report on the successful use of prey-taxon-specific
      primers in diagnostic PCR to identify, to species level, specific prey items of
      13 species of meiofaunal flatworms. Extension of this method will allow, for the
      first time, the development of a species-level understanding of trophic
      interactions among the meiofauna.

PMID- 25071365
TI  - Using a slit lamp-mounted digital high-speed camera for dynamic observation of
      phakic lenses during eye movements: a pilot study.
AB  - PURPOSE: To evaluate a digital high-speed camera combined with digital
      morphometry software for dynamic measurements of phakic intraocular lens
      movements to observe kinetic influences, particularly in fast direction changes
      and at lateral end points. MATERIALS AND METHODS: A high-speed camera taking 300
      frames per second observed movements of eight iris-claw intraocular lenses and
      two angle-supported intraocular lenses. Standardized saccades were performed by
      the patients to trigger mass inertia with lens position changes. Freeze images
      with maximum deviation were used for digital software-based morphometry analysis
      with ImageJ. RESULTS: Two eyes from each of five patients (median age 32 years,
      range 28-45 years) without findings other than refractive errors were included.
      The high-speed images showed sufficient usability for further morphometric
      processing. In the primary eye position, the median decentrations downward and in
      a lateral direction were -0.32 mm (range -0.69 to 0.024) and 0.175 mm (range 
      0.37 to 0.45), respectively. Despite the small sample size of asymptomatic
      patients, we found a considerable amount of lens dislocation. The median distance
      amplitude during eye movements was 0.158 mm (range 0.02-0.84). There was a slight
      positive correlation (r=0.39, P<0.001) between the grade of deviation in the
      primary position and the distance increase triggered by movements. CONCLUSION:
      With the use of a slit lamp-mounted high-speed camera system and morphometry
      software, observation and objective measurements of iris-claw intraocular lenses
      and angle-supported intraocular lenses movements seem to be possible. Slight
      decentration in the primary position might be an indicator of increased lens
      mobility during kinetic stress during eye movements. Long-term assessment by high
      speed analysis with higher case numbers has to clarify the relationship between
      progressing motility and endothelial cell damage.

PMID- 25071366
TI  - Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells
      through regulation of the Nrf2 pathway.
AB  - Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs) has been
      identified as a major cause of osteoporosis. However, the underlying molecular
      mechanisms accounting for this action remain elusive, which has impeded the
      prevention and cure of this side effect. Sulforaphane (SFP) is a naturally
      occurring isothiocyanate that has huge health benefits for humans. In this study,
      by using osteoblastic MC3T3-E1 cells as a model, we demonstrate the protective
      effects of SFP against dexamethasone (Dex)-induced apoptosis and elucidate the
      underlying molecular mechanisms. The results show that SFP could effectively
      inhibit the Dex-induced growth inhibition and release of lactate dehydrogenase in
      MC3T3-E1 cells. Treatment with Dex induced caspase-dependent apoptosis in MC3T3
      E1 cells, as evidenced by an increase in the Sub-G1 phase, chromatin
      condensation, and deoxyribonucleic acid fragmentation, which were significantly
      suppressed by coincubation with SFP. Mitochondria-mediated apoptosis pathway
      contributed importantly to Dex-induced apoptosis, as revealed by the activation
      of caspase-3/-9 and subsequent cleavage of poly adenosine diphosphate ribose
      polymerase, which was also effectively blocked by SFP. Moreover, treatments of
      Dex strongly induced overproduction of reactive oxygen species and inhibited the
      expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the
      downstream effectors HO1 and NQO1. However, cotreatment with SFP effectively
      reversed this action of Dex. Furthermore, silencing of Nrf2 by small interfering
      ribonucleic acid significantly blocked the cytoprotective effects of SFP against
      Dex-induced apoptosis, which suggest the important role of Nrf2 signaling pathway
      and cell apoptosis induced by Dex. Taken together, this study provides a novel
      strategy for molecular intervention against Dex-induced osteoporosis using
      phytochemicals. 

PMID- 25071367
TI  - N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic
      eczema: results of a randomized, double-blind, controlled study in 60 patients.
AB  - BACKGROUND: Asteatotic eczema (AE) is characterized by itchy, dry, rough, and
      scaling skin. The treatments for AE are mainly emollients, usually containing
      urea, lactic acid, or a lactate salt. N-palmitoylethanolamine (PEA) and N
      acetylethanolamine (AEA) are both endogenous lipids used as novel therapeutic
      tools in the treatment of many skin diseases. The purpose of this study was to
      compare a PEA/AEA emollient with a traditional emollient in the treatment of AE.
      METHODS: A monocentric, randomized, double-blind, comparative trial was conducted
      in 60 AE patients to evaluate and compare the efficacy of the two emollients. The
      level of skin dryness among the subjects ranged from mild to moderate. The
      subjects' skin barrier function and the current perception threshold were tested
      for 28 days by clinical scoring and bioengineering technology. RESULTS: The
      results showed that, although some aspects were improved in both groups, the
      group using the emollient containing PEA/AEA presented a better skin surface
      change in capacitance. However, the most impressive finding was the ability of
      the PEA/AEA emollient to increase the 5 Hz current perception threshold to a
      normal level after 7 days, with a significant difference between values at
      baseline and after 14 days. A current perception threshold of 5 Hz was positively
      and significantly correlated with skin surface hydration and negatively
      correlated with transepidermal water loss in the PEA/AEA emollient group.
      CONCLUSION: Compared with traditional emollients, regular application of a
      topical PEA/AEA emollient could improve both passive and active skin functions
      simultaneously.

PMID- 25071368
TI  - Klebsiella pneumoniae necrotizing fasciitis of the leg in an elderly French
      woman.
AB  - Klebsiella pneumoniae necrotizing fasciitis is a rare infection in regions
      outside of Asia. Here, we present a case of necrotizing fasciitis of the leg
      caused by K. pneumoniae in a 92-year-old French woman hospitalized in a geriatric
      rehabilitation unit. The patient initially presented with dermohypodermitis of
      the leg that developed from a dirty wound following a fall. A few hours later,
      this painful injury extended to the entire lower limb, with purplish
      discoloration of the skin, bullae, and necrosis. Septic shock rapidly appeared
      and the patient died 9 hours after the onset of symptoms. The patient was
      Caucasian, with no history of travel to Asia or any underlying disease. Computed
      tomography revealed no infectious metastatic loci. Blood cultures showed growth
      of capsular serotype K2 K. pneumoniae strains with virulence factors RmpA,
      yersiniabactin and aerobactin. This rare and fatal case of necrotizing fasciitis
      caused by a virulent strain of K. pneumoniae occurred in a hospitalized elderly
      woman without risk factors. Clinicians and geriatricians in particular should be
      aware of this important albeit unusual differential diagnosis. 

PMID- 25071369
TI  - A US database study characterizing patients initiating a budesonide-formoterol
      combination versus tiotropium bromide as initial maintenance therapy for chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To compare clinical and demographic characteristics, resource
      utilization and costs of chronic obstructive pulmonary disease (COPD) patients
      prior to initiating budesonide-formoterol combination (BFC) or tiotropium
      maintenance therapy. MATERIALS AND METHODS: This cross-sectional study used
      claims-based diagnosis to identify COPD patients in the HealthCore Integrated
      Research Database who initiated BFC or tiotropium therapy between March 1, 2009
      and January 31, 2012 (intake period); the index date was defined as the initial
      prescription fill for either agent. Patients diagnosed with respiratory tract
      cancer or receiving inhaled corticosteroids/long-acting beta2-adrenergic agonists
      or tiotropium in 12 months prior to index date were excluded. Categorical
      variables were evaluated with chi(2) tests; mean cost differences were evaluated
      using gamma-regression. RESULTS: Overall, 6,940 BFC and 10,831 tiotropium
      patients were identified. The BFC group was younger (mean age 64 versus 67
      years), with a greater proportion of females (54% versus 51%). BFC-treated
      patients had more comorbid respiratory conditions, including asthma (25% versus
      13%), but fewer comorbid cardiovascular conditions, including atherosclerosis (7%
      versus 10%) and myocardial infarction (4% versus 6%). A greater proportion of BFC
      patients received prior respiratory medication, including oral corticosteroids
      (46% versus 35%) and short-acting beta2-agonists (44% versus 35%). Tiotropium
      treated patients had a greater mean number of COPD-related outpatient visits (4.6
      versus 4.1). BFC-treated patients had lower total all-cause ($17,259 versus
      $17,926) and COPD-related ($1,718 versus $1,930) health care costs, driven by
      lower all-cause and COPD-related inpatient expenditures. CONCLUSION: Initiators
      of BFC or tiotropium showed differences in clinical and demographic
      characteristics and health care utilization and costs prior to starting COPD
      maintenance therapy.

PMID- 25071370
TI  - Symptoms and impact of symptoms on function and health in patients with chronic
      obstructive pulmonary disease and chronic heart failure in primary health care.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) and
      chronic heart failure (CHF) seem to have several symptoms in common that impact
      health. However, methodological differences make this difficult to compare. AIM:
      Comparisons of symptoms, impact of symptoms on function and health between
      patients with COPD and CHF in primary health care (PHC). METHOD: The study is
      cross sectional, including patients with COPD (n=437) and CHF (n=388), registered
      in the patient administrative systems of PHC. The patients received specific
      questionnaires--the Memorial Symptom Assessment Scale, the Medical Research
      Council dyspnea scale, and the Fatigue Impact Scale--by mail and additional
      questions about psychological and physical health. RESULTS: The mean age was 70
      +/- 10 years and 78 +/- 10 years for patients with COPD and CHF respectively
      (P=0.001). Patients with COPD (n=273) experienced more symptoms (11 +/- 7.5) than
      the CHF patients (n=211) (10 +/- 7.6). The most prevalent symptoms for patients
      with COPD were dyspnea, cough, and lack of energy. For patients with CHF, the
      most prevalent symptoms were dyspnea, lack of energy, and difficulty sleeping.
      Experience of dyspnea, cough, dry mouth, feeling irritable, worrying, and
      problems with sexual interest or activity were more common in patients with COPD
      while the experience of swelling of arms or legs was more common among patients
      with CHF. When controlling for background characteristics, there were no
      differences regarding feeling irritable, worrying, and sexual problems. There
      were no differences in impact of symptoms or health. CONCLUSION: Patients with
      COPD and CHF seem to experience similar symptoms. There were no differences in
      how the patients perceived their functioning according to their cardinal
      symptoms; dyspnea and fatigue, and health. An intervention for both groups of
      patients to optimize the management of symptoms and improve function is probably
      more relevant in PHC than focusing on separate diagnosis groups.

PMID- 25071371
TI  - Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D
      alpha-tocopheryl polyethylene glycol 1000 succinate nanoemulsions.
AB  - BACKGROUND: Acetylpuerarin (AP), because of its lower water solubility, shows
      poor absorption that hinders its therapeutic application. Thus, the aim of this
      study was to prepare nanoemulsions for AP, enhance its oral bioavailability, and
      thus improve the therapeutic effect. METHODS: The nanoemulsions stabilized by D
      alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by high
      pressure homogenization and characterized in terms of particle size, drug
      loading, morphology, and in vitro drug release. A lipid digestion model was used
      to predict in vivo drug solubilization in the gastrointestinal environment. The
      pharmacokinetics of AP formulations were performed in rats; meanwhile, a
      chylomicron flow-blocking rat model was used to evaluate the lymphatic drug
      transport. Moreover, the therapeutic effects of AP nanoemulsions on the model of
      focal cerebral ischemia-reperfusion for brain injury were also assessed. RESULTS:
      The nanoemulsions with a droplet size of 150 nm were well stabilized by TPGS and
      showed a high loading capacity for AP. In the digestion model, the distribution
      of AP in aqueous phase/pellet phase was about 90%/10% for nanoemulsions and
      5%/95% for oil solution, indicating that the drug encapsulated in nanoemulsions
      would present in solubilized form after transportation into the gastrointestinal
      tract, whereas drug precipitation would occur as the oil solution was orally
      administered. The area under the curve value of AP nanoemulsions was 5.76+/-0.56
      MUg.hour.mL(-1), or was about 2.6 and 1.7 times as great as that of suspension
      and oil solution, respectively, indicating enhanced drug absorption and thus
      achieving a better neuroprotection effect on cerebral ischemic reperfusion
      injury. The values of peak plasma concentration and area under the curve from the
      blocking model were significantly less than those of the control model,
      suggesting that the lymphatic transport performed a very important role in
      absorption enhancement. CONCLUSION: Enhanced oral bioavailability in
      nanoemulsions was achieved via the mechanism of the maintenance of drug
      solubilization in the gastrointestinal tract and the enhancement of lymphatic
      transport, which resulted in therapeutic improvement of cerebral ischemic
      reperfusion injury.

PMID- 25071372
TI  - Heart rate variability measurement and clinical depression in acute coronary
      syndrome patients: narrative review of recent literature.
AB  - AIM: We aimed to explore links between heart rate variability (HRV) and clinical
      depression in patients with acute coronary syndrome (ACS), through a review of
      recent clinical research literature. BACKGROUND: Patients with ACS are at risk
      for both cardiac autonomic dysfunction and clinical depression. Both conditions
      can negatively impact the ability to recover from an acute physiological insult,
      such as unstable angina or myocardial infarction, increasing the risk for adverse
      cardiovascular outcomes. HRV is recognized as a reflection of autonomic function.
      METHODS: A narrative review was undertaken to evaluate state-of-the-art clinical
      research, using the PubMed database, January 2013. The search terms "heart rate
      variability" and "depression" were used in conjunction with "acute coronary
      syndrome", "unstable angina", or "myocardial infarction" to find clinical studies
      published within the past 10 years related to HRV and clinical depression, in
      patients with an ACS episode. Studies were included if HRV measurement and
      depression screening were undertaken during an ACS hospitalization or within 2
      months of hospital discharge. RESULTS: Nine clinical studies met the inclusion
      criteria. The studies' results indicate that there may be a relationship between
      abnormal HRV and clinical depression when assessed early after an ACS event,
      offering the possibility that these risk factors play a modest role in patient
      outcomes. CONCLUSION: While a definitive conclusion about the relevance of HRV
      and clinical depression measurement in ACS patients would be premature, the
      literature suggests that these measures may provide additional information in
      risk assessment. Potential avenues for further research are proposed.

PMID- 25071373
TI  - Abciximab in the management of acute myocardial infarction with ST-segment
      elevation: evidence-based treatment, current clinical use, and future
      perspectives.
AB  - Introduction of antiplatelet agents has contributed substantially to improve the
      outcome of patients with acute coronary syndromes. Meta-analysis of the studies
      on abciximab administration during primary percutaneous coronary intervention
      (PCI) for acute ST-segment elevation myocardial infarction (STEMI) has clearly
      confirmed the mortality benefit associated with intravenous bolus and infusion of
      abciximab compared to placebo. Recently, introduction of new oral P2Y12
      inhibitors (prasugrel, ticagrelor), with a faster and more pronounced
      antiplatelet effect, have decreased the use of abciximab even in patients with
      STEMI. However, recent studies have shown a delayed onset of antiplatelet effect
      of new oral antiplatelet drugs in the setting of STEMI, especially in patients
      with hemodynamic compromise. Thus, the use of abciximab as an intravenous agent
      should be strongly considered when oral P2Y12 inhibitors might fail or cannot be
      given before primary PCI for STEMI. An additional benefit of abciximab
      administration was reported when abciximab was given early, before primary PCI,
      compared to typical periprocedural use. To the contrary, no clear clinical
      benefit was confirmed for intracoronary administration of abciximab compared with
      intravenous administration. Future studies should focus on the role of abciximab
      given on top of new oral P2Y12 inhibitor (prasugrel, ticagrelor) or used as an
      alternative to an intravenous P2Y12 inhibitor (cangrelor). Undoubtedly, the
      results of these studies will change everyday practice of STEMI treatment. 

PMID- 25071374
TI  - Circulating tumor cells in the central and peripheral venous compartment -
      assessing hematogenous dissemination after transarterial chemoembolization of
      hepatocellular carcinoma.
AB  - The aims of this study were to assess the effect of transarterial
      chemoembolization (TACE) on circulating tumor cells (CTCs) in the peripheral
      blood and right atrium of patients with HCC and to evaluate whether perioperative
      shedding of CTCs affects time to progression of HCC. Before and after TACE,
      peripheral and right atrial blood samples (7.5 mL) were collected from 42
      patients with HCC. CTCs were enriched using EpCAM antibody-conjugated magnetic
      beads. The number of CTCs was 0-30 and 0-54 in peripheral blood before and after
      TACE, respectively (P=0.166), and 0-65 and 0-98 in the right atrium before and
      after TACE, respectively (P=0.102). The number of CTCs was significantly
      different between the two samples both before (P=0.007) and after (P=0.021) TACE.
      There was no difference in time to progression between patients with and without
      an increase in the number of CTCs after TACE in either sample (P>0.05 for both).
      There were more CTCs in right atrial blood than in peripheral blood. The numbers
      of CTCs in both samples remained unchanged after TACE. Shedding of tumor cells
      did not affect time to progression of disease in patients with HCC. 

PMID- 25071375
TI  - Induction monotherapy with sirolimus has selected beneficial effects on
      glomerular and tubulointersititial injury in nephrotoxic serum nephritis.
AB  - BACKGROUND: The study aimed to test the hypothesis that therapeutic treatment
      with a mammalian target of rapamycin complex 1 inhibitor reduces renal cell
      proliferation and attenuates glomerular and tubulointerstitial injury in the
      early phase of nephrotoxic serum nephritis (NSN) in rats. METHODS: Male Wistar
      Kyoto rats received a single tail-vein injection of sheep anti-rat glomerular
      basement membrane serum (day 0) and were treated with vehicle or sirolimus (0.25
      mg/kg/day by subcutaneous injection) from day 1 until day 14. RESULTS: Treatment
      with sirolimus attenuated kidney enlargement by 41% (P<0.05), improved endogenous
      creatinine clearance by 50% (P<0.05), and reduced glomerular and
      tubulointerstitial cell proliferation by 53% and 70%, respectively, (P<0.05
      compared to vehicle) in rats with NSN. In glomeruli, sirolimus reduced segmental
      fibrinoid necrosis by 69%, autologous rat immunoglobulin G deposition, glomerular
      capillary tuft enlargement, and periglomerular myofibroblast (alpha-smooth muscle
      actin-positive cells) accumulation (all P<0.05) but did not significantly affect
      glomerular crescent formation (P=0.15), macrophage accumulation (P=0.25), or the
      progression of proteinuria. In contrast, sirolimus preserved tubulointerstitial
      structure and attenuated all markers of injury (interstitial ED-1- and alpha
      smooth muscle actin-positive cells and tubular vimentin expression; all P<0.05).
      By immunohistochemistry and Western blot analysis, sirolimus reduced the
      glomerular and tubulointerstitial expression of phosphorylated (Ser 235/236) S6
      ribosomal protein (P<0.05). CONCLUSION: Induction monotherapy with sirolimus
      suppressed target of rapamycin complex 1 activation, renal cell proliferation,
      and injury during the early stages of rodent NSN, but the degree of histological
      protection was more consistent in the tubulointerstitium than the glomerular
      compartment.

PMID- 25071376
TI  - A brief chronicle of the genus cordyceps fr., the oldest valid genus in
      cordycipitaceae (hypocreales, ascomycota).
AB  - The earliest pre-Linnaean fungal genera are briefly discussed here with special
      emphasis on the nomenclatural connection with the genus Cordyceps Fr. Since its
      valid publication under the basidiomycetous genus Clavaria Vaill. ex L. (Clavaria
      militaris L. Sp. Pl. 2:1182, 1753), the genus Cordyceps has undergone
      nomenclatural changes in the post-Linnaean era, but has stood firmly for
      approximately 200 years. Synonyms of Cordyceps were collected from different
      literature sources and analyzed based on the species they represent. True
      synonyms of Cordyceps Fr. were defined as genera that represented species of
      Cordyceps Fr. emend. G. H. Sung, J. M. Sung, Hywel-Jones & Spatafora. The most
      common synonyms of Cordyceps observed were Clavaria and Sphaeria Hall, reported
      in the 18th and in the first half of the 19th century, respectively. Cordyceps,
      the oldest genus in the Cordyceps s. s. clade of Cordycipitaceae, is the most
      preferred name under the "One Fungus = One Name" principle on priority bases. 

PMID- 25071377
TI  - Culturable fungal endophytes isolated from the roots of coastal plants inhabiting
      korean East coast.
AB  - Twelve plant species were collected from the east coast of Korea to identify
      culturable endophytes present in their roots. The fungal internal transcribe
      spacer (ITS) region (ITS1-5.8SrRNA-ITS2) was used as a DNA barcode for
      identification of fungi. A total of 194 fungal strains were identified and
      categorized into 31 genera. The genus Penicillium accounted for the largest
      number of strains, followed by the genus Aspergillus. Furthermore, using 5
      statistical methods, the diversity indices of the fungi were calculated at the
      genus level. After comprehensive evaluation, the endophytic fungal group from
      Phragmites australis ranked highest in diversity analyses. Several strains
      responsible for plant growth and survival (Penicillium citrinum, P. funiculosum,
      P. janthinellum, P. restrictum, and P. simplicissimum), were also identified.
      This study provides basic data on the sheds light on the symbiotic relationship
      between coastal plants and fungi. 

PMID- 25071378
TI  - A New Record of Penicillium antarcticum from Marine Environments in Korea.
AB  - During a survey of marine fungi from the waters surrounding Jeju Island, Korea,
      several Penicillium strains were isolated from seawater and marine sponges. Based
      on morphological characteristics and phylogenetic analyses of the internal
      transcribed spacer and RNA polymerase subunit II, four strains were identified as
      Penicillium antarcticum, a fungus that, to the best of our knowledge, had not
      been previously reported in Korea. Here, we provide detailed descriptions of the
      morphological characteristics and extracellular enzyme activities of the four
      strains. 

PMID- 25071379
TI  - Re-evaluation of the Genus Antrodia (Polyporales, Basidiomycota) in Korea.
AB  - The wood decay fungi Antrodia P. Karst. play important ecological roles and have
      significant industrial and economic impacts as both wood degraders and sources of
      pharmaceutical and biotechnological products. Although each Antrodia species has
      distinct morphological characteristics, the misidentification rate is especially
      high due to their simple morphological characters. A combination of morphological
      and internal transcribed spacer region sequence analyses revealed that 27 of 89
      specimens previously identified by morphology alone were correct, whereas 35 of
      these specimens were misidentified as other Antrodia species. We report here that
      seven Antrodia species exist in Korea (A. albida, A. heteromorpha, A. malicola,
      A. serialis, A. sinuosa, A. sitchensis, and A. xantha) and based on these
      specimens, we provide taxonomic descriptions of these species, except for A.
      serialis, which was only confirmed by isolate. 

PMID- 25071380
TI  - Notes on the lichen genus leptogium (collemataceae, ascomycota) in South Korea.
AB  - Leptogium (Ach.) Gray is distributed throughout South Korea; however, for nearly
      two decades no detailed taxonomic or revisionary research on this lichen genus
      has been conducted. This study examined the specimens deposited in the lichen
      herbarium at the Korean Lichen Research Institute, and samples were identified
      using descriptions recently published in the scientific literature. In this
      revisionary study, a total of fourteen species of Leptogium were documented,
      including new records of Leptogium delavayi Hue, Leptogium denticulatum Nyl., and
      Leptogium trichophoroides P. M. Jorg. & A. K. Wallace. Detailed descriptions of
      each species are given, including their morphological, anatomical, and chemical
      characteristics. A key to all Leptogium species known to occur in South Korea is
      also presented. 

PMID- 25071381
TI  - A checklist of the basidiomycetous macrofungi and a record of five new species
      from mt. Oseo in Korea.
AB  - Basidiomycetous macrofungi play important roles in maintaining forest ecosystems
      via carbon cycling and the mobilization of nitrogen and phosphorus. To understand
      the impact of human activity on macrofungi, an ongoing project at the Korea
      National Arboretum is focused on surveying the macrofungi in unexploited areas.
      Mt. Oseo was targeted in this survey because the number of visitors to this
      destination has been steadily increasing, and management and conservation plans
      for this destination are urgently required. Through 5 field surveys of Mt. Oseo
      from April to October 2012, 116 specimens of basidiomycetous macrofungi were
      collected and classified. The specimens were identified to the species level by
      analyzing their morphological characteristics and their DNA sequence data. A
      total of 80 species belonging to 57 genera and 25 families were identified. To
      the best of our knowledge, this is the first study to identify five of these
      species-Artomyces microsporus, Hymenopellis raphanipes, Pholiota abietis,
      Phylloporus brunneiceps, and Sirobasidium magnum-in Korea. 

PMID- 25071382
TI  - Wood decay fungi in South Korea: polypores from seoul.
AB  - In Seoul, a majority of plant communities have undergone significant changes over
      the last few decades; however, how wood decay fungi have responded and adapted to
      the changes in vegetation remains unknown. Through an ongoing investigation of
      Korean indigenous fungi, ca. 300 specimens with poroid basidiocarp were collected
      in Seoul during 2008~2012. Morphological examination and molecular analysis using
      the internal transcribed spacer and nuclear large subunit ribosomal DNA region
      sequences helped identify 38 species belonging to 28 genera, 10 families, and 5
      orders in this area. Among them, three polypores, Abundisporus pubertatis,
      Coriolopsis strumosa, and Perenniporia maackiae were found to be new to South
      Korea. 

PMID- 25071383
TI  - Diversity of endophytic fungi isolated from korean ginseng leaves.
AB  - We investigated the diversity of the foliar endophytes of Korean ginseng.
      Endophytic fungi were isolated from healthy leaves of mountain-cultivated ginseng
      (MCG) and field-cultivated ginseng (FCG) at 4 sites in Chungbuk Province. A total
      of 24 species of fungal endophytes were identified using molecular approaches.
      Additionally, the diversity of these endophytic fungi was compared between MCG
      and FCG. The major isolated endophytes were Edenia gomezpompae and Gibberella
      moniliformis in the MCG and FCG samples, respectively. The results suggest that
      ginseng endophytes have different community structures in different environments,
      and this understanding may prove useful in ginseng cultivation. 

PMID- 25071384
TI  - A Ferroxidase, Cfo1, Regulates Diverse Environmental Stress Responses of
      Cryptococcus neoformans through the HOG Pathway.
AB  - The iron uptake and utilization pathways play a critical role in allowing human
      pathogens, including Cryptococcus neoformans, the causative agent of fatal
      meningoencephalitis, to survive within the mammalian body by competing with the
      host for iron. Here we show that the iron regulon is also required for diverse
      environmental stress responses and that in C. neoformans, it is regulated by the
      high-osmolarity glycerol response (HOG) pathway. Between CFO1 and CFO2, two
      ferroxidase genes in the iron regulon, CFO1 but not CFO2 was induced during
      oxidative and osmotic stress. Interestingly, we found that the HOG pathway
      repressed basal expression of both CFO1 and CFO2. Furthermore, when the HOG
      pathway was blocked, CFO2 also responded to oxidative and osmotic stress and the
      response of CFO1 was increased. We also established that CFO1 plays a major role
      in responding and adapting to diverse environmental stresses, including oxidative
      and genotoxic damage, osmotic fluctuations, heavy metal stress, and stress
      induced by cell membrane destabilizers. Therefore, our findings indicate that in
      C. neoformans, the iron uptake and utilization pathways are not only required for
      iron acquisition and survival, but also play a significant role in the
      environmental stress response through crosstalk with the HOG pathway. 

PMID- 25071385
TI  - Biocontrol of fusarium crown and root rot and promotion of growth of tomato by
      paenibacillus strains isolated from soil.
AB  - In this study, bacterial strains were isolated from soils from 30 locations of
      Samcheok, Gangwon province. Of the isolated strains, seven showed potential plant
      growth promoting and antagonistic activities. Based on cultural and morphological
      characterization, and 16S rRNA gene sequencing, these strains were identified as
      Paenibacillus species. All seven strains produced ammonia, cellulase, hydrocyanic
      acid, indole-3-acetic acid, protease, phosphatase, and siderophores. They also
      inhibited the mycelial growth of Fusarium oxysporum f. sp. radicis-lycopersici in
      vitro. The seven Paenibacillus strains enhanced a range of growth parameters in
      tomato plants under greenhouse conditions, in comparison with non-inoculated
      control plants. Notably, treatment of tomato plants with one identified strain,
      P. polymyxa SC09-21, resulted in 80.0% suppression of fusarium crown and root rot
      under greenhouse conditions. The plant growth promoting and antifungal activity
      of P. polymyxa SC09-21 identified in this study highlight its potential
      suitability as a bioinoculant. 

PMID- 25071386
TI  - Cloning and Molecular Characterization of beta-1,3-Glucan Synthase from Sparassis
      crispa.
AB  - A beta-glucan synthase gene was isolated from the genomic DNA of polypore
      mushroom Sparassis crispa, which reportedly produces unusually high amount of
      soluble beta-1,3-glucan (beta-glucan). Sequencing and subsequent open reading
      frame analysis of the isolated gene revealed that the gene (5,502 bp) consisted
      of 10 exons separated by nine introns. The predicted mRNA encoded a beta-glucan
      synthase protein, consisting of 1,576 amino acid residues. Comparison of the
      predicted protein sequence with multiple fungal beta-glucan synthases estimated
      that the isolated gene contained a complete N-terminus but was lacking
      approximately 70 amino acid residues in the C-terminus. Fungal beta-glucan
      synthases are integral membrane proteins, containing the two catalytic and two
      transmembrane domains. The lacking C-terminal part of S. crispa beta-glucan
      synthase was estimated to include catalytically insignificant transmembrane alpha
      helices and loops. Sequence analysis of 101 fungal beta-glucan synthases,
      obtained from public databases, revealed that the beta-glucan synthases with
      various fungal origins were categorized into corresponding fungal groups in the
      classification system. Interestingly, mushrooms belonging to the class
      Agaricomycetes were found to contain two distinct types (Type I and II) of beta
      glucan synthases with the type-specific sequence signatures in the loop regions.
      S. crispa beta-glucan synthase in this study belonged to Type II family, meaning
      Type I beta-glucan synthase is expected to be discovered in S. crispa. The high
      productivity of soluble beta-glucan was not explained but detailed biochemical
      studies on the catalytic loop domain in the S. crispa beta-glucan synthase will
      provide better explanations. 

PMID- 25071387
TI  - Genetic Diversity and Pathogenicity of Cylindrocarpon destructans Isolates
      Obtained from Korean Panax ginseng.
AB  - We analyzed the genetic diversity of Cylindrocarpon destructans isolates obtained
      from Korean ginseng (i.e., Panax ginseng) roots by performing virulence tests and
      nuclear ribosomal gene internal transcribed spacer (ITS) and mitochondrial small
      subunit (mt SSU) rDNA sequence analysis. The phylogenetic relationship analysis
      performed using ITS DNA sequences and isolates from other hosts helped confirm
      that all the Korean C. destructans isolates belonged to Nectria/Neonectria
      radicicola complex. The results of in vivo and ex vivo virulence tests showed
      that the C. destructans isolates could be divided into two groups according to
      their distinctive difference in virulence and the genetic diversity. The highly
      virulent Korean isolates in pathogenicity group II (PG II), together with foreign
      isolates from P. ginseng and P. quinquefolius, formed a single group. The weakly
      virulent isolates in pathogenicity group I, together with the foreign isolates
      from other host plants, formed another group and exhibited a greater genetic
      diversity than the isolates of PG II, as confirmed by the mt SSU rDNA sequence
      analysis. In addition, as the weakly virulent Korean isolates were genetically
      very similar to the foreign isolates from other hosts, they were likely to
      originate from hosts other than the ginseng plants. 

PMID- 25071388
TI  - Isolation and analysis of the enzymatic properties of thermophilic fungi from
      compost.
AB  - To the best of our knowledge, this is the first report on thermophilic fungi
      isolated in Korea. Three species of thermophiles were isolated from compost and
      were identified as Myriococcum thermophilum, Thermoascus aurantiacus, and
      Thermomyces lanuginosus. They can grow at temperatures above 50C and produce high
      levels of cellulolytic and xylanolytic enzymes at high temperatures. Notably, the
      considerable thermostability of the endo-glucanase produced by T. aurantiacus has
      made the fungus an attractive source of industrial enzymes. 

PMID- 25071389
TI  - Lipoxygenase Inhibitory Activity of Korean Indigenous Mushroom Extracts and
      Isolation of an Active Compound from Phellinus baumii.
AB  - We investigated a total of 335 samples of Korean native mushroom extracts as part
      of our lipoxygenase (LOX) inhibitor screening program. Among the mushroom
      methanolic extracts we investigated, 35 exhibited an inhibitory activity greater
      than 30% against LOX at a concentration of 100 ug/mL. Especially, Collybia
      maculata, Tylopilus neofelleus, Strobilomyces confusus, Phellinus gilvus, P.
      linteus, P. baumii, and Inonotus mikadoi exhibited relatively potent LOX
      inhibitory activities of 73.3%, 51.6%, 52.4%, 66.7%, 59.5%, 100.0%, and 85.2%,
      respectively. Bioassay-guided fractionation led to the isolation of inoscavin A
      from the methanolic extract of P. baumii, which showed the most potent activity
      and was identified by spectroscopic methods. Specifically, inoscavin A exhibited
      potent LOX inhibitory activity with an IC50 value of 6.8 uM. 

PMID- 25071390
TI  - Neuraminidase Inhibitors from the Fermentation Broth of Phellinus linteus.
AB  - During a search for neuraminidase inhibitors derived from medicinal fungi, we
      found that the fermentation broth of Phellinus linteus exhibited potent
      neuraminidase inhibitory activity. Through bioassay-guided fractionation, two
      active compounds were purified from the ethyl acetate-soluble portion of the
      fermentation broth of P. linteus. These structures were identified as inotilone
      (1) and 4-(3,4-dihydroxyphenyl)-3-buten-2-one (2) by spectroscopic methods.
      Compounds 1 and 2 inhibited H1N1 neuraminidase activity with IC50 values of 29.1
      and 125.6 uM, respectively, in a dose-dependent manner. They also exhibited an
      antiviral effect in a viral cytopathic effect reduction assay using MDCK cells.
      These results suggest that compounds 1 and 2 from the culture broth of P. linteus
      would be good candidates for the prevention and therapeutic strategies towards
      viral infections. 

PMID- 25071391
TI  - Overproduction of Laccase by the White-Rot Fungus Pleurotus ostreatus Using Apple
      Pomace as Inducer.
AB  - Laccase activity of Pleurotus ostreatus is significantly increased by the
      addition of apple pomace. Among various conditions, the best concentration of
      apple pomace and cultivation time for the production of laccase by P. ostreatus
      was 2.5% and 9 days, respectively. Reverse transcription polymerase chain
      reaction analyses of laccase isoenzyme genes, including pox1, pox3, pox4, poxc,
      poxa3, and poxa1b, revealed a clear effect of apple pomace on transcription
      induction. Our findings reveal that the use of apple pomace can be a model for
      the valuable addition of similar wastes and for the development of a solid-state
      fermenter and commercial production of oyster mushroom P. ostreatus. 

PMID- 25071392
TI  - Microbiological characteristics and physiological functionality of new records of
      yeasts from wild flowers in yokjido, Korea.
AB  - Two new yeast records, Cryptococcus adeliensis YJ19-2 and Cryptococcus
      uzbekistanensis YJ10-4 were screened from 60 yeasts strains that were isolated
      and identified from wild flowers in Yokjido, Gyeongsangnam-do, Korea. The
      morphological and cultural characteristics of the newly recorded yeasts and the
      physiological functionalities of the supernatants and cell-free extracts obtained
      from their cultures were investigated. The two newly recorded yeasts did not form
      ascospores and pseudomycelia. They also grew well in yeast extract-peptone
      dextrose broth. C. uzbekistanensis YJ10-4 grew in a vitamin-free medium and was
      also tolerant to sugar and salt. Antihypertensive angiotensin I-converting enzyme
      inhibitory activity of the supernatant from C. adeliensis YJ19-2 was high (71.8%)
      and its cell-free extract also showed very high (81.2%) antidiabetic a
      glucosidase inhibitory activity. 

PMID- 25071393
TI  - First Report of Myrothecium roridum Causing Leaf and Stem Rot Disease on
      Peperomia quadrangularis in Korea.
AB  - In 2010, symptoms of leaf and stem rot were observed on potted plants (Peperomia
      quadrangularis) in a greenhouse in Yongin, Korea. The causative pathogen was
      identified as Myrothecium roridum based on morphological data, internal
      transcribed spacer sequence analysis, and pathogenicity test. To our knowledge,
      this is the first report of M. roridum causing leaf and stem rot disease on P.
      quadrangularis in Korea and elsewhere worldwide. 

PMID- 25071394
TI  - First Report of Potato Stem-End Rot Caused by Fusarium oxysporum in Korea.
AB  - In this study, we identified the causative agent of stem-end rot in potatoes that
      were grown in Gangwon alpine areas of Korea in 2013. The disease symptoms
      included appearance of slightly sunken circular lesion with corky rot on the
      potato surface at the stem-end portion. The fungal species isolated from the
      infected potatoes were grown on potato dextrose agar and produced white aerial
      mycelia with dark violet pigments. The conidiophores were branched and
      monophialidic. The microconidia had ellipsoidal to cylindrical shapes and ranged
      from 2.6~11.4 * 1.9~3.5 um in size. The macroconidia ranged from 12.7~24.7 *
      2.7~3.6 um in size and had slightly curved or fusiform shape with 2 to 5 septate.
      Chlamydospores ranged from 6.1~8.1 * 5.7~8.3 um in size and were present singly
      or in pairs. The causal agent of potato stem-end rot was identified as Fusarium
      oxysporum by morphological characterization and by sequencing the internal
      transcribed spacer (ITS1 and ITS4) regions of rRNA. Artificial inoculation of the
      pathogen resulted in development of disease symptoms and the re-isolated pathogen
      showed characteristics of F. oxysporum. To the best of our knowledge, this is the
      first study to report that potato stem-end rot is caused by F. oxysporum in
      Korea. 

PMID- 25071395
TI  - The Effect of Raffaelea quercus-mongolicae Inoculations on the Formation of Non
      conductive Sapwood of Quercus mongolica.
AB  - In Korea, mass mortality of Quercus mongolica trees has become obvious since
      2004. Raffaelea quercus-mongolicae is believed to be a causal fungus contributing
      the mortality. To evaluate the pathogenicity of the fungus to the trees, the
      fungus was multiple- and single-inoculated to the seedlings and twigs of the
      mature trees, respectively. In both the inoculations, the fungus was reisolated
      from more than 50% of inoculated twigs and seedlings. In the single inoculations,
      proportions of the transverse area of non-conductive sapwood at inoculation
      points and vertical lengths of discoloration expanded from the points were
      significantly different between the inoculation treatment and the control. In the
      multiple inoculations, no mortality was confirmed among the seedlings examined.
      These results showed that R. quercus-mongolicae can colonize sapwood, contribute
      to sapwood discoloration and disrupt sap flows around inoculation sites of Q.
      mongolica, although the pathogenicity of the fungus was not proven. 

PMID- 25071396
TI  - Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin
      America.
AB  - This review aims to provide clinicians in Latin America with the most current
      information on the clinical aspects, diagnosis, and management of Hunter
      syndrome, a serious and progressive disease for which specific treatment is
      available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase
      (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient.
      Clinical manifestations vary widely in severity and involve multiple organs and
      tissues. An attenuated and a severe phenotype are recognized depending on the
      degree of cognitive impairment. Early diagnosis is vital for disease management.
      Clinical signs common to children with Hunter syndrome include inguinal hernia,
      frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone
      dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based
      on screening urinary glycosaminoglycans and confirmation by measuring I2S
      activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S)
      (Elaprase((r)), Shire) enzyme replacement therapy (ERT), designed to address the
      underlying enzyme deficiency, is approved treatment and improves walking capacity
      and respiratory function, and reduces spleen and liver size and urinary
      glycosaminoglycan levels. Additional measures, responding to the multi-organ
      manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery,
      and cardiac valve replacement, should also be considered. Investigational
      treatment options such as intrathecal ERT are active areas of research, and bone
      marrow transplantation is in clinical practice. Communication among care
      providers, social workers, patients and families is essential to inform and guide
      their decisions, establish realistic expectations, and assess patients'
      responses. 

PMID- 25071398
TI  - Genetic polymorphisms of Interleukin-18 are not associated with allograft
      function in kidney transplant recipients.
AB  - Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host
      defense by upregulating both innate and acquired immune responses. Analysis of
      IL18 polymorphisms may be clinically important since their roles have been
      recognized in a variety of inflammatory and autoimmune disorders. However, the
      role of this cytokine polymorphisms in kidney transplant still remains unclear.
      In this study, we evaluated the associations between IL18 polymorphisms and graft
      function assessed by creatinine clearance in kidney transplant recipients. A
      total of 82 kidney transplant recipients and 183 healthy controls were enrolled,
      and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were
      determined and compared with creatinine clearance. The -607C/A (rs1946518) and 
      137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase
      chain reaction. In our study, no significant association was found between the
      IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism
      analysis revealed an increase in the frequency of the IL18 major haplotype -607C/
      137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45
      4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence
      the renal function and that IL18 haplotype -607C/-137G seems to be associated
      with kidney transplant recipients. 

PMID- 25071397
TI  - Identification of selection signatures in livestock species.
AB  - The identification of regions that have undergone selection is one of the
      principal goals of theoretical and applied evolutionary genetics. Such studies
      can also provide information about the evolutionary processes involved in shaping
      genomes, as well as physical and functional information about genes/genomic
      regions. Domestication followed by breed formation and selection schemes has
      allowed the formation of very diverse livestock breeds adapted to a wide variety
      of environments and with special characteristics. The advances in genomics in the
      last five years have enabled the development of several methods to detect
      selection signatures and have resulted in the publication of a considerable
      number of studies involving livestock species. The aims of this review are to
      describe the principal effects of natural/artificial selection on livestock
      genomes, to present the main methods used to detect selection signatures and to
      discuss some recent results in this area. This review should be useful also to
      research scientists working with wild animals/non-domesticated species and plant
      biologists working with breeding and evolutionary biology. 

PMID- 25071399
TI  - Genetic polymorphisms and haplotypes of the organic cation transporter 1 gene
      (SLC22A1) in the Xhosa population of South Africa.
AB  - Human organic cation transporter 1 is primarily expressed in hepatocytes and
      mediates the electrogenic transport of various endogenous and exogenous
      compounds, including clinically important drugs. Genetic polymorphisms in the
      gene coding for human organic cation transporter 1, SLC22A1, are increasingly
      being recognized as a possible mechanism explaining the variable response to
      clinical drugs, which are substrates for this transporter. The genotypic and
      allelic distributions of 19 nonsynonymous and one intronic SLC22A1 single
      nucleotide polymorphisms were determined in 148 healthy Xhosa participants from
      South Africa, using a SNAPshot((r)) multiplex assay. In addition, haplotype
      structure for SLC22A1 was inferred from the genotypic data. The minor allele
      frequencies for S14F (rs34447885), P341L (rs2282143), V519F (rs78899680), and the
      intronic variant rs622342 were 1.7%, 8.4%, 3.0%, and 21.6%, respectively. None of
      the participants carried the variant allele for R61C (rs12208357), C88R
      (rs55918055), S189L (rs34104736), G220V (rs36103319), P283L (rs4646277), R287G
      (rs4646278), G401S (rs34130495), M440I (rs35956182), or G465R (rs34059508). In
      addition, no variant alleles were observed for A306T (COSM164365), A413V
      (rs144322387), M420V (rs142448543), I421F (rs139512541), C436F (rs139512541),
      V501E (rs143175763), or I542V (rs137928512) in the population. Eight haplotypes
      were inferred from the genotypic data. This study reports important genetic data
      that could be useful for future pharmacogenetic studies of drug transporters in
      the indigenous Sub-Saharan African populations. 

PMID- 25071400
TI  - Association between human papillomavirus (HPV) DNA and micronuclei in normal
      cervical cytology.
AB  - The aim of the present study was to investigate the association between HPV-DNA
      and micronucleus (MN) frequency in women with normal cervical cytology. A total
      of 158 normal cervical smears were analyzed cytologically. The HPV genome was
      amplified using the GP5+/bioGP6+ consensus primers. HPV-DNA of high-risk types
      16, 18, 31, 33, 39, 45 and 59 were also investigated. Of the 158 samples, 20
      (12.7%) and 47 (29.7%) were positive for HPV-DNA and MN, respectively. Evidence
      for MN was found in 11 out of 20 (55%) HPV-DNA positive samples and in 36 out of
      138 (26.1%) HPV-DNA negative ones. MN presence was significantly higher in HPV
      DNA positive samples (p = 0.016). On the other hand, the absence of MN observed
      in a considerable number of HPV-DNA negative samples (102) may be of great value
      in predicting the absence of HPV. The mean age of HPV-DNA positive women (34.2 +/
      12.6) was significantly lower than the mean age of HPV-DNA negative women (43.9
      +/- 13.7) (p = 0.003). Infection by one or multiple HPV types was found in 11 out
      of 20 (55.0%) and 9 out of 20 (45.0%) samples, respectively. The evaluation of MN
      using cervical smears collected for cytology tests could, thus, be used as
      additional information to monitor a population's exposure to HPV. 

PMID- 25071402
TI  - Karyotypic evolution of ribosomal sites in buffalo subspecies and their
      crossbreed.
AB  - DOMESTIC BUFFALOES ARE DIVIDED INTO TWO GROUP BASED ON CYTOGENETIC
      CHARACTERISTICS AND HABITATS: the "river buffaloes" with 2n = 50 and the "swamp
      buffaloes", 2n = 48. Nevertheless, their hybrids are viable, fertile and
      identified by a 2n = 49. In order to have a better characterization of these
      different cytotypes of buffaloes, and considering that NOR-bearing chromosomes
      are involved in the rearrangements responsible for the karyotypic differences, we
      applied silver staining (Ag-NOR) and performed fluorescent in situ hybridization
      (FISH) experiments using 18S rDNA as probe. Metaphases were obtained through
      blood lymphocyte culture of 21 individuals, including river, swamp and hybrid
      cytotypes. Ag-NOR staining revealed active NORs on six chromosome pairs (3p, 4p,
      6, 21, 23, 24) in the river buffaloes, whereas the swamp buffaloes presented only
      five NOR-bearing pairs (4p, 6, 20, 22, 23). The F1 cross-breed had 11 chromosomes
      with active NORs, indicating expression of both parental chromosomes. FISH
      analysis confirmed the numerical divergence identified with Ag-NOR. This result
      is explained by the loss of the NOR located on chromosome 4p in the river
      buffalo, which is involved in the tandem fusion with chromosome 9 in this
      subspecies. A comparison with the ancestral cattle karyotype suggests that the
      NOR found on the 3p of the river buffalo may have originated from a duplication
      of ribosomal genes, resulting in the formation of new NOR sites in this
      subspecies. 

PMID- 25071401
TI  - Sex determination in annual fishes: Searching for the master sex-determining gene
      in Austrolebias charrua (Cyprinodontiformes, Rivulidae).
AB  - Evolution of sex determination and differentiation in fishes involves a broad
      range of sex strategies (hermaphroditism, gonochorism, unisexuality,
      environmental and genetic sex determination). Annual fishes inhabit temporary
      ponds that dry out during the dry season when adults die. The embryos exhibit an
      atypical developmental pattern and remain buried in the bottom mud until the next
      rainy season. To elucidate genomic factors involved in the sex determination in
      annual fish, we explored the presence of a candidate sex-specific gene related to
      the cascade network in Austrolebias charrua. All phylogenetic analyses showed a
      high posterior probability of occurrence for a clade integrated by nuclear
      sequences (aprox. 900 bp) from both adults (male and female), with partial cDNA
      fragments of A. charrua from juveniles (male) and the dsx D. melanogaster gene.
      The expressed fragment was detected from blastula to adulthood stages showing a
      sexually dimorphic expression pattern. The isolated cDNA sequence is clearly
      related to dsx D. melanogaster gene and might be located near the top of the sex
      determination cascade in this species. 

PMID- 25071403
TI  - Characterization and expression analysis of chymotrypsin after bacterial
      challenge in the mud crab, Scylla paramamosain.
AB  - Chymotrypsin is one of the serine proteases families that have various biological
      functions. A chymotrypsin gene was isolated from hepatopancreas of the mud crab,
      Scylla paramamosain (designated SpCHY) in this study. The full-length cDNA of
      SpCHY contained 942 nucleotides with a polyadenylation sequence and encoded a
      peptide of 270 amino acids with a signal peptide of 17 amino acids. The SpCHY
      gene contains seven exons, six introns, a TATA box and several transcription
      factor binding sites that were found in 5'-promoter region which is 1221 bp in
      length. Real-time quantitative PCR analysis indicated that the expression level
      of SpCHY mRNA in hepatopancreas was significantly higher than that in other
      tissues. Immunocytochemistry and in situ hybridization exhibited the CHY-like
      reactivity presented in resorptive cells of the hepatopancreas. After bacterial
      challenge with Vibrio alginolyticus, the expression level of SpCHY mRNA was
      extremely up-regulated at 3 h in hepatopancreas. Our results suggest that SpCHY
      might play an important role in the mud crab's immune response. 

PMID- 25071404
TI  - Genomic variation and population structure detected by single nucleotide
      polymorphism arrays in Corriedale, Merino and Creole sheep.
AB  - THE AIM OF THIS STUDY WAS TO INVESTIGATE THE GENETIC DIVERSITY WITHIN AND AMONG
      THREE BREEDS OF SHEEP: Corriedale, Merino and Creole. Sheep from the three breeds
      (Merino n = 110, Corriedale n = 108 and Creole n = 10) were genotyped using the
      Illumina Ovine SNP50 beadchip((r)). Genetic diversity was evaluated by comparing
      the minor allele frequency (MAF) among breeds. Population structure and genetic
      differentiation were assessed using STRUCTURE software, principal component
      analysis (PCA) and fixation index (FST). Fixed markers (MAF = 0) that were
      different among breeds were identified as specific breed markers. Using a subset
      of 18,181 single nucleotide polymorphisms (SNPs), PCA and STUCTURE analysis were
      able to explain population stratification within breeds. Merino and Corriedale
      divergent lines showed high levels of polymorphism (89.4% and 86% of polymorphic
      SNPs, respectively) and moderate genetic differentiation (FST = 0.08) between
      them. In contrast, Creole had only 69% polymorphic SNPs and showed greater
      genetic differentiation from the other two breeds (FST = 0.17 for both breeds).
      Hence, a subset of molecular markers present in the OvineSNP50 is informative
      enough for breed assignment and population structure analysis of commercial and
      Creole breeds. 

PMID- 25071405
TI  - Genetic diversity and symbiotic compatibility among rhizobial strains and
      Desmodium incanum and Lotus spp. plants.
AB  - This work aimed to evaluate the symbiotic compatibility and nodulation efficiency
      of rhizobia isolated from Desmodium incanum, Lotus corniculatus, L. subbiflorus,
      L. uliginosus and L. glaber plants by cross-inoculation. Twelve reference strains
      and 21 native isolates of rhizobia were genetically analyzed by the BOX-PCR
      technique, which showed a high genetic diversity among the rhizobia studied. The
      isolates were also characterized based on their production of indolic compounds
      and siderophores, as well as on their tolerance to salinity. Fifteen of the 33
      rhizobia analyzed were able to produce indolic compounds, whereas 13 produced
      siderophores. All the tested rhizobia were sensitive to high salinity, although
      some were able to grow in solutions of up to 2% NaCl. Most of the native rhizobia
      isolated from L. uliginosus were able to induce nodulation in all plant species
      studied. In a greenhouse experiment using both D. incanum and L. corniculatus
      plants, the rhizobia isolate UFRGS Lu2 promoted the greatest plant growth. The
      results demonstrate that there are native rhizobia in the soils of southern
      Brazil that have low host specificity and are able to induce nodulation and form
      active nodules in several plant species. 

PMID- 25071406
TI  - Characterization and mapping of a spotted leaf mutant in rice (Oryza sativa).
AB  - Spotted leaf mutant belongs to a class of mutants that can produce necrotic
      lesions spontaneously in plants without any attack by pathogens. These mutants
      have no beneficial effect on plant productivity but provide a unique opportunity
      to study programmed cell death in plant defense responses. A novel rice spotted
      leaf mutant (spl30) was isolated through low-energy heavy ion irradiation. Lesion
      expression was sensitive to light and humidity. The spl30 mutant caused a
      decrease in chlorophyll and soluble protein content, with marked accumulation of
      reactive oxygen species (ROS) around the lesions. In addition, the spl30 mutant
      significantly enhanced resistance to rice bacterial blight (X. oryzae pv. oryzae)
      from China (C1-C7). The use of SSR markers showed that the spl30 gene was located
      between markers XSN2 and XSN4. The genetic distance between the spl30 gene and
      XSN2 and between spl30 and XSN4 was 1.7 cM and 0.2 cM, respectively. The spl30
      gene is a new gene involved in lesion production and may be related to programmed
      cell death in rice. The ability of this mutant to confer broad resistance to
      bacterial blight provides a model for studying the interaction between plants and
      pathogenic bacteria. 

PMID- 25071407
TI  - An effective homologous cloning method for isolating novel miR172s from
      Phalaenopsis hybrida.
AB  - MiR172 is an important microRNA that regulates floral development in various
      plants and downregulates AP2 family members to relieve the stress on floral
      determinacy, leading to phase transition from vegetative to reproductive growth.
      In this work, PCR with primers designed based on the rice miR172 sequence was
      used to isolate two miR172-like transcripts from Phalaenopsis hybrida (PhmiR172-1
      and PhmiR172-2) that were very similar to Oryza miR172d and Arabidopsis miR172b.
      RT-PCR indicated that the levels of these two transcripts were negatively
      correlated with the level of the Phalaenopsis AP2 (PhAP2) gene in stem, root,
      pedicel and sepal, and that both were co-expressed with PhAP2 in young buds.
      Overproduction of PhmiR172-2 in Arabidopsis led to early flowering. The
      homologous cloning method used to isolate the Phalaenopsis miR172-like
      transcripts can be used to isolate miRNAs from other species. These PhmiR172
      transcripts may be used to accelerate the flowering of orchids. 

PMID- 25071408
TI  - Phylogeny and molecular dating of the cerato-platanin-encoding genes.
AB  - The cerato-platanin family consists of proteins that can induce immune responses,
      cause necrosis, change chemotaxis and locomotion and may be related to the growth
      and development of various fungi. In this work, we analyzed the phylogenetic
      relationships among genes encoding members of the cerato-platanin family and
      computed the divergence times of the genes and corresponding fungi. The results
      showed that cerato-platanin-encoding genes could be classified into 10 groups but
      did not cluster according to fungal classes or their functions. The genes
      transferred horizontally and showed duplication. Molecular dating and adaptive
      evolution analyses indicated that the cerato-platanin gene originated with the
      appearance of saprophytes and that the gene was under positive selection. This
      finding suggests that cerato-platanin-encoding genes evolved with the development
      of fungal parasitic characteristics. 

PMID- 25071409
TI  - Evaluation of the mutagenicity and antimutagenicity of Ziziphus joazeiro Mart.
      bark in the micronucleus assay.
AB  - The aim of this study was to evaluate the mutagenicity
      (clastogenicity/aneugenicity) of a glycolic extract of Ziziphus joazeiro bark
      (GEZJ) by the micronucleus assay in mice bone marrow. Antimutagenic activity was
      also assessed using treatments associated with GEZJ and doxorubicin (DXR). Mice
      were evaluated 24-48 h after exposure to positive (N-nitroso-N-ethylurea, NEU -
      50 mg.kg(-1) and DXR - 5 mg.kg(-1)) and negative (150 mM NaCl) controls, as well
      as treatment with GEZJ (0.5-2 g.kg(-1)), GEZJ (2 g.kg(-1)) + NEU and GEZJ (2
      g.kg(-1)) + DXR. There were no significant differences in the frequencies of
      micronucleated polychromatic erythrocytes in mice treated with GEJZ and GEJZ +
      DXR compared to the negative controls, indicating that GEZJ was not mutagenic.
      Analysis of the polychromatic:normochromatic erythrocyte ratio revealed
      significant differences in the responses to doses of 0.5 g.kg(-1) and 1-2 g.kg(
      1) and the positive control (NEU). These results indicated no systemic toxicity
      and moderate toxicity at lower and higher doses of GEZJ. The lack of mutagenicity
      and systemic toxicity in the antimutagenic assays, especially for treatment with
      GEZJ + DXR, suggested that phytochemical compounds in Z. joazeiro bark attenuated
      DXR-induced mutagenicity and the moderate systemic toxicity of a high dose of Z.
      joazeiro bark (2 g.kg(-1)). Further studies on the genotoxicity of Z. joazeiro
      extracts are necessary to establish the possible health risk in humans and to
      determine the potential as a chemopreventive agent for therapeutic use. 

PMID- 25071410
TI  - DNA methylation dynamics in the rat EGF gene promoter after partial hepatectomy.
AB  - Epidermal growth factor (EGF), a multifunctional growth factor, is a regulator in
      a wide variety of physiological processes. EGF plays an important role in the
      regulation of liver regeneration. This study was aimed at investigating the
      methylation level of EGF gene throughout liver regeneration. DNA of liver tissue
      from control rats and partial hepatectomy (PH) rats at 10 time points was
      extracted and a 354 bp fragment including 10 CpG sites from the transcription
      start was amplified after DNA was modified by sodium bisulfate. The result of
      sequencing suggested that methylation ratio of four CpG sites was found to be
      significantly changed when PH group was compared to control group, in particular
      two of them were extremely striking. mRNA expression of EGF was down-regulated in
      total during liver regeneration. We think that the rat EGF promoter region is
      regulated by variation in DNA methylation during liver regeneration. 

PMID- 25071411
TI  - Genome-wide comparison of genes involved in the biosynthesis, metabolism, and
      signaling of juvenile hormone between silkworm and other insects.
AB  - Juvenile hormone (JH) contributes to the regulation of larval molting and
      metamorphosis in insects. Herein, we comprehensively identified 55 genes involved
      in JH biosynthesis, metabolism and signaling in the silkworm (Bombyx mori) as
      well as 35 in Drosophila melanogaster, 35 in Anopheles gambiae, 36 in Apis
      mellifera, 47 in Tribolium castaneum, and 44 in Danaus plexippus. Comparative
      analysis showed that each gene involved in the early steps of the mevalonate
      (MVA) pathway, in the neuropeptide regulation of JH biosynthesis, or in JH
      signaling is a single copy in B. mori and other surveyed insects, indicating that
      these JH-related pathways or steps are likely conserved in all surveyed insects.
      However, each gene participating in the isoprenoid branch of JH biosynthesis and
      JH metabolism, together with the FPPS genes for catalyzing the final step of the
      MVA pathway of JH biosynthesis, exhibited an obvious duplication in Lepidoptera,
      including B. mori and D. plexippus. Microarray and real-time RT-PCR analysis
      revealed that different copies of several JH-related genes presented expression
      changes that correlated with the dynamics of JH titer during larval growth and
      metamorphosis. Taken together, the findings suggest that duplication-derived copy
      variation of JH-related genes might be evolutionarily associated with the
      variation of JH types between Lepidoptera and other insect orders. In conclusion,
      our results provide useful clues for further functional analysis of JH-related
      genes in B. mori and other insects. 

PMID- 25071412
TI  - Searching for convergent evolution in manganese superoxidase dismutase using
      hydrophobic cluster analysis.
AB  - There are numerous examples of convergent evolution in nature. Major ecological
      adaptations such as flight, loss of limbs in vertebrates, pesticide resistance,
      adaptation to a parasitic way of life, etc., have all evolved more than once, as
      seen by their analogous functions in separate taxa. But what about protein
      evolution? Does the environment have a strong enough influence on intracellular
      processes that enzymes and other functional proteins play, to evolve similar
      functional roles separately in different organisms? Manganese Superoxide
      Dismutase (MnSOD) is a manganesedependant metallo-enzyme which plays a crucial
      role in protecting cells from anti-oxidative stress by eliminating reactive
      (superoxide) oxygen species. It is a ubiquitous housekeeping enzyme found in
      nearly all organisms. In this study we compare phylogenies based on MnSOD protein
      sequences to those based on scores from Hydrophobic Cluster Analysis (HCA). We
      calculated HCA similarity values for each pair of taxa to obtain a pair-wise
      distance matrix. A UPGMA tree based on the HCA distance matrix and a common tree
      based on the primary protein sequence for MnSOD was constructed. Differences
      between these two trees within animals, enterobacteriaceae, planctomycetes and
      cyanobacteria are presented and cited as possible examples of convergence. We
      note that several residue changes result in changes in hydrophobicity at
      positions which apparently are under the effect of positive selection. 

PMID- 25071413
TI  - Multifaceted diversity-area relationships reveal global hotspots of mammalian
      species, trait and lineage diversity.
AB  - AIM: To define biome-scale hotspots of phylogenetic and functional mammalian
      biodiversity (PD and FD, respectively) and compare them to 'classical' hotspots
      based on species richness (SR) only. LOCATION: Global. METHODS: SR, PD & FD were
      computed for 782 terrestrial ecoregions using distribution ranges of 4616
      mammalian species. We used a set of comprehensive diversity indices unified by a
      recent framework that incorporates the species relative coverage in each
      ecoregion. We build large-scale multifaceted diversity-area relationships to rank
      ecoregions according to their levels of biodiversity while accounting for the
      effect of area on each diversity facet. Finally we defined hotspots as the top
      ranked ecoregions. RESULTS: While ignoring species relative coverage led to a
      relative good congruence between biome top ranked SR, PD and FD hotspots,
      ecoregions harboring a rich and abundantly represented evolutionary history and
      functional diversity did not match with top ranked ecoregions defined by species
      richness. More importantly PD and FD hotspots showed important spatial
      mismatches. We also found that FD and PD generally reached their maximum values
      faster than species richness as a function of area. MAIN CONCLUSIONS: The fact
      that PD/FD reach faster their maximal value than SR may suggest that the two
      former facets might be less vulnerable to habitat loss than the latter. While
      this point is expected, it is the first time that it is quantified at global
      scale and should have important consequences in conservation. Incorporating
      species relative coverage into the delineation of multifaceted hotspots of
      diversity lead to weak congruence between SR, PD and FD hotspots. This means that
      maximizing species number may fail at preserving those nodes (in the phylogenetic
      or functional tree) that are relatively abundant in the ecoregion. As a
      consequence it may be of prime importance to adopt a multifaceted biodiversity
      perspective to inform conservation strategies at global scale.

PMID- 25071415
TI  - The impact of performance status and comorbidities on the short-term prognosis of
      very elderly patients admitted to the ICU.
AB  - BACKGROUND: Patients >=80 years of age are increasingly being admitted to the
      intensive care unit (ICU). The impact of relevant variables, such comorbidities
      and performance status, on short-term outcomes in the very elderly is largely
      unknown. Few studies address the calibration of illness severity scores (SAPS3
      score) within this population. We investigated the risk factors for hospital
      mortality in critically ill patients >=80 years old, emphasizing performance
      status and comorbidities, and assessed the calibration of SAPS3 scores in this
      population. METHODS: 1129 very elderly patients admitted to a tertiary ICU in
      Brazil during a two-year period were retrospectively included in this study.
      Demographic features, reasons for admission, illness severity, comorbidities
      (including the Charlson Comorbidity Index) and a simplified performance status
      measurement were obtained. After univariate analysis, a multivariate model was
      created to evaluate the factors that were associated with hospital mortality.
      Alternatively, a conditional inference tree with recursive partitioning was
      constructed. Calibration of the SAPS3 scores and the multivariate model were
      evaluated using the Hosmer-Lemeshow test and a calibration plot. Discrimination
      was assessed using a receiver operating characteristics curve. RESULTS: On
      multivariate analysis after stepwise regression, only the SAPS3 score (OR 1.08,
      95% CI 1.06-1.10), Charlson Index (OR 1.16, 95% CI 1.07-1.27), performance status
      (OR 1.61, 95% CI 1.05-2.64 for partially dependent patients and OR 2.39, 95% CI
      1.38-4.13 for fully dependent patients) and a non-full code status (OR 11.74, 95%
      CI 6.22-22.160) were associated with increased hospital mortality. Conditional
      inference tree showed that performance status and Charlson Index had the greatest
      influence on patients with less severe disease, whereas a non-full code status
      was prominent in patients with higher illness severity (SAPS3 score >61). The
      model obtained after logistic regression that included the before mentioned
      variables demonstrated better calibration and greater discrimination capability
      (AUC 0.86, 95% CI 0.83-0.89 versus AUC 0.81, 95% CI 0.78-0.84, respectively; p <
      0.001) than the SAPS3 score alone. CONCLUSIONS: Performance status and
      comorbidities are important determinants of short-term outcome in critically ill
      elderly patients >=80 years old. The addition of simple background information
      may increase the calibration of the SAPS3 score in this population.

PMID- 25071414
TI  - Does an additional structured information program during the intensive care unit
      stay reduce anxiety in ICU patients?: a multicenter randomized controlled trial.
AB  - BACKGROUND: Communication and information in order to reduce anxiety in the
      intensive care unit (ICU) has been described as area needing improvement.
      Therefore, the aim of this trial was to evaluate whether a structured information
      program that intensifies information given in standard care process reduces
      anxiety in ICU patients. METHODS: Multicenter, two-armed, non-blinded, parallel
      group randomized controlled trial in hospitals in the cities of Marburg, Halle,
      and Stuttgart (Germany). The trial was performed in cardiac surgery, general
      surgery, and internal medicine ICUs. Two-hundred and eleven elective and non
      elective ICU patients were enrolled in the study (intervention group, n = 104;
      control group, n = 107). The experimental intervention comprised a single episode
      of structured oral information that was given in addition to standard care and
      covered two main parts: (1) A more standardized part about predefined ICU
      specific aspects - mainly procedural, sensory and coping information, and (2) an
      individualized part about fears and questions of the patient. The control group
      received a non-specific episodic conversation of similar length additional to
      standard care. Both conversations took place at the beginning of the ICU stay and
      lasted 10-15 minutes. Study nurses administered both interventions. The primary
      outcome ICU-related anxiety (CINT-Score, 0-100 pts., higher scores indicate
      higher anxiety) was assessed after admission to a regular ward. RESULTS: The
      primary outcome could be measured in 82 intervention group participants and 90
      control group participants resulting in mean values of 20.4 (SD 14.4) compared to
      20.8 (SD 14.7) and a mean difference of -0.2 (CI 95% -4.5 to 4.1). CONCLUSIONS: A
      structured information intervention additional to standard care during ICU stay
      had no demonstrated additional benefit compared to an unspecific communication of
      similar duration. Reduction of anxiety in ICU patients will probably require more
      continuous approaches to information giving and communication. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00764933.

PMID- 25071416
TI  - Feasibility of assessing quality of care at the end of life in two cluster trials
      using an after-death approach with multiple assessments.
AB  - BACKGROUND: In 2009 two randomised cluster trials took place to assess the
      introduction of the Italian Version of the Liverpool Care Pathway in hospitals
      and hospices. Before and after data were gathered. The primary aim of this study
      is to evaluate the feasibility of using a combination of assessment methods aimed
      at different proxy respondents to create a means of measuring quality of care at
      the end of life. We also aim to explore whether there are differences in response
      to this approach between the hospice and hospital inpatient settings. METHODS: A
      retrospective design was used. Eligible deaths were traced through death
      registries, and proxies were used to give information. Four procedures of
      assessment were used to measure different dimensions. Feasibility was assessed
      through compliance and adherence to the study instruments, and measured against
      standards derived from previous after-death studies. The proxy caregiver's rating
      of the study tools was also measured, to gauge feasibility and effectiveness. All
      consecutive cancer deaths that occurred in the study period were eligible. In
      both trials, deaths were excluded if the patient was a relative of
      hospital/hospice staff. 145 patients were recruited from the Hospital setting,
      and 127 from Hospice. RESULTS: A high proportion of non-professional caregivers
      were interviewed - in both hospital (76.6%) and hospice (74.8%). There was no
      significant difference in the median number of days in each setting. 89.0% of
      hospital patients' GPs and 85.0% of hospice patients' GPs were interviewed. Care
      procedures were recorded in all hospice cases, and were missing in only 1
      hospital case.52.7% of Hospital patients' relatives and 64.12% Hospice relatives
      were assessed to have been caused a low level of distress through the study.
      CONCLUSIONS: The data shows high levels of compliance and adherence to the study
      instruments. This suggests that this approach to assessing quality of care is
      feasible, and this coupled with low levels of distress caused by the study
      instruments suggest effectiveness. There were no substantial differences between
      the hospice and hospital settings.

PMID- 25071418
TI  - Tannic acid label indicates abnormal cell development coinciding with
      regeneration of renal tubules.
AB  - BACKGROUND: Stem/progenitor cells are in the focus of research as a future
      therapeutic option to stimulate regeneration in diseased renal parenchyma.
      However, current data indicate that successful seeding of implanted
      stem/progenitor cells is prevented by harmful interstitial fluid and altered
      extracellular matrix. To find out possible parameters for cell adaptation, the
      present investigation was performed. METHODS: Renal stem/progenitor cells were
      mounted in an artificial interstitium for perfusion culture. Exposure to
      chemically defined but CO2-independent culture media was tested during 13 days.
      Cell biological features were then analyzed by histochemistry, while structural
      details were investigated by transmission electron microscopy after conventional
      and improved fixation of specimens. RESULTS: Culture of renal stem/progenitor
      cells as well in Leibovitz's L-15 Medium as CO2 Independent Medium shows in
      fluorescence microscopy spatial development of numerous tubules. Specimens of
      both media fixed by conventional glutaraldehyde exhibit in electron microscopy a
      homogeneous cell population in developed tubules. In contrast, fixation by
      glutaraldehyde including tannic acid illuminates that dispersed dark marked cells
      of unknown function are present. The screening further demonstrates that the dark
      cell type does not comply with cells found in embryonic, maturing or matured
      renal parenchyma. CONCLUSIONS: The actual data show that development of abnormal
      cell features must be taken into account, when regeneration of renal tubules is
      simulated under in vitro conditions.

PMID- 25071417
TI  - Cross-reactivity of steroid hormone immunoassays: clinical significance and two
      dimensional molecular similarity prediction.
AB  - BACKGROUND: Immunoassays are widely used in clinical laboratories for measurement
      of plasma/serum concentrations of steroid hormones such as cortisol and
      testosterone. Immunoassays can be performed on a variety of standard clinical
      chemistry analyzers, thus allowing even small clinical laboratories to do
      analysis on-site. One limitation of steroid hormone immunoassays is interference
      caused by compounds with structural similarity to the target steroid of the
      assay. Interfering molecules include structurally related endogenous compounds
      and their metabolites as well as drugs such as anabolic steroids and synthetic
      glucocorticoids. METHODS: Cross-reactivity of a structurally diverse set of
      compounds were determined for the Roche Diagnostics Elecsys assays for cortisol,
      dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone.
      These data were compared and contrasted to package insert data and published
      cross-reactivity studies for other marketed steroid hormone immunoassays. Cross
      reactivity was computationally predicted using the technique of two-dimensional
      molecular similarity. RESULTS: The Roche Elecsys Cortisol and Testosterone II
      assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol
      II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high
      cross-reactivity for the cortisol assay, with high likelihood of clinically
      significant effect for patients administered these drugs. In addition, 21
      deoxycortisol likely produces clinically relevant cross-reactivity for cortisol
      in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce
      clinically relevant cross-reactivity in 11beta-hydroxylase deficiency or
      following metyrapone challenge. Several anabolic steroids may produce clinically
      significant false positives on the testosterone assay, although interpretation is
      limited by sparse pharmacokinetic data for some of these drugs. Norethindrone
      therapy may impact immunoassay measurement of testosterone in women. Using two
      dimensional similarity calculations, all compounds with high cross-reactivity
      also showed a high degree of similarity to the target molecule of the
      immunoassay. CONCLUSIONS: Compounds producing cross-reactivity in steroid hormone
      immunoassays generally have a high degree of structural similarity to the target
      hormone. Clinically significant interactions can occur with structurally similar
      drugs (e.g., prednisolone and cortisol immunoassays; methyltestosterone and
      testosterone immunoassays) or with endogenous compounds such as 21-deoxycortisol
      that can accumulate to very high concentrations in certain disease conditions.
      Simple similarity calculations can help triage compounds for future testing of
      assay cross-reactivity.

PMID- 25071419
TI  - Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary
      adenocarcinomas: development and utility of a potential diagnostic
      immunohistochemistry panel.
AB  - BACKGROUND: Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis.
      Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory
      cytology. Cytological interpretation can be difficult especially in the setting
      of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could
      act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta
      analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in
      PBA resection specimens. METHODS: Tissue microarrays containing tumour and normal
      cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for
      IHC. IHC was performed on an automated platform using antibodies against KOC,
      S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and
      proportion of tissue stained using a Histoscore method (range, 0-300).
      Sensitivity and specificity for individual biomarkers, as well as biomarker
      panels, were determined with different cut-offs for positivity and compared by
      summary receiver operating characteristic (ROC) curve. RESULTS: The expression of
      all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore
      of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200
      vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully
      chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%,
      10% or 20% positive cells and Histoscore 20 were identified using ROC curve
      analysis and the fifth cut-off was moderate-strong staining intensity. Using 20%
      positive cells as a cut-off achieved higher sensitivity/specificity values: KOC
      84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a
      panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity
      if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and
      specificity for 20% cut-off. CONCLUSION: A biomarker panel of KOC, S100P and
      mesothelin with at least 2 biomarkers positive was found to be an optimum panel
      with both 10% and 20% cut-offs in resection specimens from patients with PBA.

PMID- 25071420
TI  - Proteomic analysis of laser capture microscopy purified myotendinous junction
      regions from muscle sections.
AB  - The myotendinous junction is a specialized structure of the muscle fibre enriched
      in mechanosensing complexes, including costameric proteins and core elements of
      the z-disc. Here, laser capture microdissection was applied to purify membrane
      regions from the myotendinous junctions of mouse skeletal muscles, which were
      then processed for proteomic analysis. Sarcolemma sections from the longitudinal
      axis of the muscle fibre were used as control for the specificity of the
      junctional preparation. Gene ontology term analysis of the combined lists
      indicated a statistically significant enrichment in membrane-associated proteins.
      The myotendinous junction preparation contained previously uncharacterized
      proteins, a number of z-disc costameric ligands (e.g., actinins, capZ, alphaB
      cristallin, filamin C, cypher, calsarcin, desmin, FHL1, telethonin, nebulin,
      titin and an enigma-like protein) and other proposed players of sarcomeric
      stretch sensing and signalling, such as myotilin and the three myomesin homologs.
      A subset were confirmed by immunofluorescence analysis as enriched at the
      myotendinous junction, suggesting that laser capture microdissection from muscle
      sections is a valid approach to identify novel myotendinous junction players
      potentially involved in mechanotransduction pathways. 

PMID- 25071421
TI  - Cry babies and pollyannas: Infants can detect unjustified emotional reactions.
AB  - Infants are attuned to emotional facial and vocal expressions, reacting most
      prominently when they are exposed to negative expressions. However, it remains
      unknown if infants can detect whether a person's emotions are justifiable given a
      particular context. The focus of the current paper was to examine whether infants
      react the same way to unjustified (e.g., distress following a positive
      experience) and justified (e.g., distress following a negative experience)
      emotional reactions. Infants aged 15 and 18 months were shown an actor
      experiencing negative and positive experiences, with one group exposed to an
      actor whose emotional reactions were consistently unjustified (i.e., did not
      match the event), while the other saw an actor whose emotional reactions were
      justified (i.e., always matched the event). Infants' looking times and empathic
      reactions were examined. Only 18-month-olds detected the mismatching facial
      expressions: those in the unjustified group showed more hypothesis testing (i.e.,
      checking) across events than the justified group. Older infants in the justified
      group also showed more concerned reactions to negative expressions than those in
      the unjustified group. The present findings indicate that infants implicitly
      understand how the emotional valence of experiences is linked to subsequent
      emotional expressions.

PMID- 25071422
TI  - Explore Arctic Health.
AB  - The Arctic Health web site is a portal to Arctic-specific, health related
      content. The site provides expertly organized and annotated resources pertinent
      to northern peoples and places, including health information, research
      publications and environmental information. This site also features the Arctic
      Health Publications Database, which indexes an array of Arctic-related resources.

PMID- 25071423
TI  - Biomimetic Aerobic C-H Olefination of Cyclic Enaminones at Room Temperature:
      Development toward the Synthesis of 1,3,5-Trisubstituted Benzenes.
AB  - A green and mild protocol for the dehydrogenative olefination of cyclic
      enaminones was devised via palladium catalysis at room temperature using oxygen
      as the terminal oxidant. The synthetic utility of the olefinated cyclic
      enaminones afforded a series of unique 1,3,5-trisubstituted benzenes via an
      unanticipated Diels-Alder tandem reaction. The broad substrate scope and good
      yields achieved with this new protocol provide an alternative pathway for arene
      functionalization.

PMID- 25071424
TI  - Partitioning two components of BOLD activation suppression in flanker effects.
AB  - The presence of a visual stimulus not only increases the blood oxygenation level
      dependent (BOLD) activation in its retinotopic regions in the visual cortex but
      also suppresses the activation of the nearby regions. Here we investigated
      whether there are multiple components for such lateral effects by using the m
      sequence paradigm to measure the stimulus spatial configuration specific BOLD
      activation. The central target (2 cyc/deg grating) was centered on a fixation
      point while the flanking stimulus was placed 2 degrees  away and was located on
      axes that were either collinear or orthogonal to the target's orientation. Three
      types of flankers were used: gratings whose orientation was the same as the
      central stimulus, gratings which were orthogonal to the stimulus, and random
      dots. The onset and offset of each stimulus were determined by shifted copies of
      an 8-bit long m-sequence. The duration of each state of the sequence was 2 s or
      1TR. The first order activation, computed as the waveform recorded following on
      states minus that recorded after off-states, determined the retinotopic regions
      for each stimulus. We then computed BOLD activation waveforms for the target
      under various flanker conditions. All flankers reduced the activation to the
      target. The suppressive effect was largest following the presence of the iso
      orientation collinear flankers. Our result suggests two types of BOLD signal
      suppression: general suppression, which occurs whenever a flanker is presented
      and is insensitive to the spatial configuration of the stimuli, and spatial
      configuration dependent suppression, which may be related to the collinear
      flanker effect. 

PMID- 25071425
TI  - Which fMRI clustering gives good brain parcellations?
AB  - Analysis and interpretation of neuroimaging data often require one to divide the
      brain into a number of regions, or parcels, with homogeneous characteristics, be
      these regions defined in the brain volume or on the cortical surface. While
      predefined brain atlases do not adapt to the signal in the individual subject
      images, parcellation approaches use brain activity (e.g., found in some
      functional contrasts of interest) and clustering techniques to define regions
      with some degree of signal homogeneity. In this work, we address the question of
      which clustering technique is appropriate and how to optimize the corresponding
      model. We use two principled criteria: goodness of fit (accuracy), and
      reproducibility of the parcellation across bootstrap samples. We study these
      criteria on both simulated and two task-based functional Magnetic Resonance
      Imaging datasets for the Ward, spectral and k-means clustering algorithms. We
      show that in general Ward's clustering performs better than alternative methods
      with regard to reproducibility and accuracy and that the two criteria diverge
      regarding the preferred models (reproducibility leading to more conservative
      solutions), thus deferring the practical decision to a higher level alternative,
      namely the choice of a trade-off between accuracy and stability. 

PMID- 25071426
TI  - Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term
      effects of early exercise.
AB  - Adult neurogenesis is highly responsive to environmental and physiological
      factors. The majority of studies to date have examined short-term consequences of
      enhancing or blocking neurogenesis but long-term changes remain less well
      understood. Current evidence for age-related declines in neurogenesis warrant
      further investigation into these long-term changes. In this report we address the
      hypothesis that early life experience, such as a period of voluntary running in
      juvenile rats, can alter properties of adult neurogenesis for the remainder of
      the animal's life. The results indicate that the number of proliferating and
      differentiating neuronal precursors is not altered in runners beyond the initial
      weeks post-running, suggesting homeostatic regulation of these processes.
      However, the rate of neuronal maturation and survival during a 4 week period
      after cell division was enhanced up to 11 months of age (the end of the study
      period). This study is the first to show that a transient period of physical
      activity at a young age promotes changes in neurogenesis that persist over the
      long-term, which is important for our understanding of the modulation of
      neurogenesis by exercise with age. Functional integration of adult-born neurons
      within the hippocampus that resist homeostatic regulation with aging, rather than
      the absolute number of adult-born neurons, may be an essential feature of adult
      neurogenesis that promotes the maintenance of neural plasticity in old age. 

PMID- 25071427
TI  - Data-driven analysis of simultaneous EEG/fMRI using an ICA approach.
AB  - Due to its millisecond-scale temporal resolution, EEG allows to assess neural
      correlates with precisely defined temporal relationship relative to a given
      event. This knowledge is generally lacking in data from functional magnetic
      resonance imaging (fMRI) which has a temporal resolution on the scale of seconds
      so that possibilities to combine the two modalities are sought. Previous
      applications combining event-related potentials (ERPs) with simultaneous fMRI
      BOLD generally aimed at measuring known ERP components in single trials and
      correlate the resulting time series with the fMRI BOLD signal. While it is a
      valuable first step, this procedure cannot guarantee that variability of the
      chosen ERP component is specific for the targeted neurophysiological process on
      the group and single subject level. Here we introduce a newly developed data
      driven analysis procedure that automatically selects task-specific
      electrophysiological independent components (ICs). We used single-trial
      simultaneous EEG/fMRI analysis of a visual Go/Nogo task to assess inhibition
      related EEG components, their trial-to-trial amplitude variability, and the
      relationship between this variability and the fMRI. Single-trial EEG/fMRI
      analysis within a subgroup of 22 participants revealed positive correlations of
      fMRI BOLD signal with EEG-derived regressors in fronto-striatal regions which
      were more pronounced in an early compared to a late phase of task execution. In
      sum, selecting Nogo-related ICs in an automated, single subject procedure reveals
      fMRI-BOLD responses correlated to different phases of task execution.
      Furthermore, to illustrate utility and generalizability of the method beyond
      detecting the presence or absence of reliable inhibitory components in the EEG,
      we show that the IC selection can be extended to other events in the same
      dataset, e.g., the visual responses. 

PMID- 25071428
TI  - The musician effect: does it persist under degraded pitch conditions of cochlear
      implant simulations?
AB  - Cochlear implants (CIs) are auditory prostheses that restore hearing via
      electrical stimulation of the auditory nerve. Compared to normal acoustic
      hearing, sounds transmitted through the CI are spectro-temporally degraded,
      causing difficulties in challenging listening tasks such as speech
      intelligibility in noise and perception of music. In normal hearing (NH),
      musicians have been shown to better perform than non-musicians in auditory
      processing and perception, especially for challenging listening tasks. This
      "musician effect" was attributed to better processing of pitch cues, as well as
      better overall auditory cognitive functioning in musicians. Does the musician
      effect persist when pitch cues are degraded, as it would be in signals
      transmitted through a CI? To answer this question, NH musicians and non-musicians
      were tested while listening to unprocessed signals or to signals processed by an
      acoustic CI simulation. The task increasingly depended on pitch perception: (1)
      speech intelligibility (words and sentences) in quiet or in noise, (2) vocal
      emotion identification, and (3) melodic contour identification (MCI). For speech
      perception, there was no musician effect with the unprocessed stimuli, and a
      small musician effect only for word identification in one noise condition, in the
      CI simulation. For emotion identification, there was a small musician effect for
      both. For MCI, there was a large musician effect for both. Overall, the effect
      was stronger as the importance of pitch in the listening task increased. This
      suggests that the musician effect may be more rooted in pitch perception, rather
      than in a global advantage in cognitive processing (in which musicians would have
      performed better in all tasks). The results further suggest that musical training
      before (and possibly after) implantation might offer some advantage in pitch
      processing that could partially benefit speech perception, and more strongly
      emotion and music perception. 

PMID- 25071429
TI  - Sexually dimorphic nuclei in the spinal cord control male sexual functions.
AB  - Lower spinal cord injuries frequently cause sexual dysfunction in men, including
      erectile dysfunction and an ejaculation disorder. This indicates that the
      important neural centers for male sexual function are located within the lower
      spinal cord. It is interesting that the lumbar spinal segments contain several
      neural circuits, showing a clear sexually dimorphism that, in association with
      neural circuits of the thoracic and sacral spinal cord, are critical in
      expressing penile reflexes during sexual behavior. To date, many sex differences
      in the spinal cord have been discovered. Interestingly, most of these are male
      dominant. Substantial evidence of sexually dimorphic neural circuits in the
      spinal cord have been reported in many animal models, but major issues remain
      unknown. For example, it is not known how the different circuits cooperatively
      function during male sexual behavior. In this review, therefore, the anatomical
      and functional significance of the sexually dimorphic nuclei in the spinal cord
      corresponding to the expression of male sexual behavior is discussed. 

PMID- 25071430
TI  - Electrophysiological characterization of male goldfish (Carassius auratus)
      ventral preoptic area neurons receiving olfactory inputs.
AB  - Chemical communication via sex pheromones is critical for successful reproduction
      but the underlying neural mechanisms are not well-understood. The goldfish is a
      tractable model because sex pheromones have been well-characterized in this
      species. We used male goldfish forebrain explants in vitro and performed whole
      cell current clamp recordings from single neurons in the ventral preoptic area
      (vPOA) to characterize their membrane properties and synaptic inputs from the
      olfactory bulbs (OB). Principle component and cluster analyses based on intrinsic
      membrane properties of vPOA neurons (N = 107) revealed five (I-V) distinct cell
      groups. These cells displayed differences in their input resistance (Rinput: I <
      II < IV < III = V), time constant (TC: I = II < IV < III = V), and threshold
      current (Ithreshold: I > II = IV > III = V). Evidence from electrical stimulation
      of the OB and application of receptor antagonists suggests that vPOA neurons
      receive monosynaptic glutamatergic inputs via the medial olfactory tract, with
      connectivity varying among neuronal groups [I (24%), II (40%), III (0%), IV
      (34%), and V (2%)]. 

PMID- 25071431
TI  - Pairmate-dependent pup retrieval as parental behavior in male mice.
AB  - Appropriate parental care by fathers can greatly facilitate healthy human family
      life. However, much less is known about paternal behavior in animals compared to
      those regarding maternal behavior. Previously, we reported that male ICR strain
      laboratory mice, although not spontaneously parental, can be induced to display
      maternal-like parental care (pup retrieval) when separated from their pups by
      signals from the pairmate dam (Liu et al., 2013). This parental behavior by the
      ICR sires, which are not genetically biparental, is novel and has been designated
      as pairmate-dependent paternal behavior. However, the factors critical for this
      paternal behavior are unclear. Here, we report that the pairmate-dependent
      paternal retrieval behavior is observed especially in the ICR strain and not in
      C57BL/6 or BALB/c mice. An ICR sire displays retrieval behavior only toward his
      biological pups. A sire co-housed with an unrelated non-pairing dam in a new
      environment, under which 38-kHz ultrasonic vocalizations are not detected, does
      not show parenting behavior. It is important for sires to establish their own
      home territory (cage) by continuous housing and testing to display retrieval
      behavior. These results indicated that the ICR sires display distinct paternity,
      including father-child social interaction, and shed light on parental behavior,
      although further analyses of paternal care at the neuroendocrinological and
      neurocircuitry levels are required. 

PMID- 25071432
TI  - Function of basal ganglia in bridging cognitive and motor modules to perform an
      action.
AB  - The basal ganglia (BG) are thought to be involved in the integration of multiple
      sources of information, and their dysfunction can lead to disorders such as
      Parkinson's disease (PD). PD patients show motor and cognitive dysfunction with
      specific impairments in the internal generation of motor actions and executive
      deficits, respectively. The role of the BG, then, would be to integrate
      information from several sources in order to make a decision on a resulting
      action adequate for the required task. Reanalyzing the data set from our previous
      study (Martinu et al., 2012), we investigated this hypothesis by applying a graph
      theory method to a series of fMRI data during the performance of self-initiated
      (SI) finger movement tasks obtained in healthy volunteers (HV) and early stage PD
      patients. Dorsally, connectivity strength between the medial prefrontal areas
      (mPFC) and cortical regions including the primary motor area (M1), the
      extrastriate visual cortex, and the associative cortex, was reduced in the PD
      patients. The connectivity strengths were positively correlated to activity in
      the striatum in both groups. Ventrally, all connectivity between the striatum,
      the thalamus, and the extrastriate visual cortex decreased in strength in the PD,
      as did the connectivity between the striatum and the ventrolateral PFC (VLPFC).
      Individual response time (RT) was negatively correlated to connectivity strength
      between the dorsolateral PFC (DLPFC) and the striatum and positively correlated
      to connectivity between the VLPFC and the striatum in the HV. These results
      indicate that the BG, with the mPFC and thalamus, are involved in integrating
      multiple sources of information from areas such as DLPFC, and VLPFC, connecting
      to M1, thereby determining a network that leads to the adequate decision and
      performance of the resulting action. 

PMID- 25071433
TI  - Single-sided deafness and directional hearing: contribution of spectral cues and
      high-frequency hearing loss in the hearing ear.
AB  - Direction-specific interactions of sound waves with the head, torso, and pinna
      provide unique spectral-shape cues that are used for the localization of sounds
      in the vertical plane, whereas horizontal sound localization is based primarily
      on the processing of binaural acoustic differences in arrival time (interaural
      time differences, or ITDs) and sound level (interaural level differences, or
      ILDs). Because the binaural sound-localization cues are absent in listeners with
      total single-sided deafness (SSD), their ability to localize sound is heavily
      impaired. However, some studies have reported that SSD listeners are able, to
      some extent, to localize sound sources in azimuth, although the underlying
      mechanisms used for localization are unclear. To investigate whether SSD
      listeners rely on monaural pinna-induced spectral-shape cues of their hearing ear
      for directional hearing, we investigated localization performance for low-pass
      filtered (LP, <1.5 kHz), high-pass filtered (HP, >3kHz), and broadband (BB, 0.5
      20 kHz) noises in the two-dimensional frontal hemifield. We tested whether
      localization performance of SSD listeners further deteriorated when the pinna
      cavities of their hearing ear were filled with a mold that disrupted their
      spectral-shape cues. To remove the potential use of perceived sound level as an
      invalid azimuth cue, we randomly varied stimulus presentation levels over a broad
      range (45-65 dB SPL). Several listeners with SSD could localize HP and BB sound
      sources in the horizontal plane, but inter-subject variability was considerable.
      Localization performance of these listeners strongly reduced after diminishing of
      their spectral pinna-cues. We further show that inter-subject variability of SSD
      can be explained to a large extent by the severity of high-frequency hearing loss
      in their hearing ear. 

PMID- 25071434
TI  - Music in disorders of consciousness.
AB  - This review presents an overview of the use of music therapy in neurological
      early rehabilitation of patients with coma and other disorders of consciousness
      (DOC) such as unresponsive wakefulness syndrome (UWS) or minimally conscious
      state (MCS). There is evidence that patients suffering from UWS show emotional
      processing of auditory information, such as listening to speech. Thus, it seems
      reasonable to believe that music listening-as part of an enriched environment
      setting-may be of therapeutic value in these patients. There is, however, a
      considerable lack of evidence. The authors strongly encourage further studies to
      evaluate the efficacy of music listening in patients with DOC in neurological
      early rehabilitation. These studies should consider a precise clinical definition
      and homogeneity of the patient cohort with respect to the quality (coma vs. UWS
      vs. MCS), duration (rather weeks to months than days) and cause (traumatic vs.
      non-traumatic) of DOC, a standardized intervention protocol, valid clinical
      outcome parameters over a longer observation period (weeks to months), monitoring
      of neurophysiological and vegetative parameters and, if available, neuroimaging
      to confirm diagnosis and to demonstrate responses and functional changes in the
      patients' brains. 

PMID- 25071435
TI  - Missing data estimation in fMRI dynamic causal modeling.
AB  - Dynamic Causal Modeling (DCM) can be used to quantify cognitive function in
      individuals as effective connectivity. However, ambiguity among subjects in the
      number and location of discernible active regions prevents all candidate models
      from being compared in all subjects, precluding the use of DCM as an individual
      cognitive phenotyping tool. This paper proposes a solution to this problem by
      treating missing regions in the first-level analysis as missing data, and
      performing estimation of the time course associated with any missing region using
      one of four candidate methods: zero-filling, average-filling, noise-filling using
      a fixed stochastic process, or one estimated using expectation-maximization. The
      effect of this estimation scheme was analyzed by treating it as a preprocessing
      step to DCM and observing the resulting effects on model evidence. Simulation
      studies show that estimation using expectation-maximization yields the highest
      classification accuracy using a simple loss function and highest model evidence,
      relative to other methods. This result held for various dataset sizes and varying
      numbers of model choice. In real data, application to Go/No-Go and Simon tasks
      allowed computation of signals from the missing nodes and the consequent
      computation of model evidence in all subjects compared to 62 and 48 percent
      respectively if no preprocessing was performed. These results demonstrate the
      face validity of the preprocessing scheme and open the possibility of using
      single-subject DCM as an individual cognitive phenotyping tool. 

PMID- 25071436
TI  - Risk taking under stress: the role(s) of self-selection. A comment on Buckert et
      al. (2014).

PMID- 25071438
TI  - Neuron-specific protein interactions of Drosophila CASK-beta are revealed by mass
      spectrometry.
AB  - Modular scaffolding proteins are designed to have multiple interactors. CASK, a
      member of the membrane-associated guanylate kinase (MAGUK) superfamily, has been
      shown to have roles in many tissues, including neurons and epithelia. It is
      likely that the set of proteins it interacts with is different in each of these
      diverse tissues. In this study we asked if within the Drosophila central nervous
      system, there were neuron-specific sets of CASK-interacting proteins. A YFP
      tagged CASK-beta transgene was expressed in genetically defined subsets of
      neurons in the Drosophila brain known to be important for CASK function, and
      proteins present in an anti-GFP immunoprecipitation were identified by mass
      spectrometry. Each subset of neurons had a distinct set of interacting proteins,
      suggesting that CASK participates in multiple protein networks and that these
      networks may be different in different neuronal circuits. One common set of
      proteins was associated with mitochondria, and we show here that endogenous CASK
      beta co-purifies with mitochondria. We also determined CASK-beta
      posttranslational modifications for one cell type, supporting the idea that this
      technique can be used to assess cell- and circuit-specific protein modifications
      as well as protein interaction networks. 

PMID- 25071437
TI  - Membrane guanylate cyclase, a multimodal transduction machine: history, present,
      and future directions.
AB  - A sequel to these authors' earlier comprehensive reviews which covered the field
      of mammalian membrane guanylate cyclase (MGC) from its origin to the year 2010,
      this article contains 13 sections. The first is historical and covers MGC from
      the year 1963-1987, summarizing its colorful developmental stages from its
      passionate pursuit to its consolidation. The second deals with the establishment
      of its biochemical identity. MGC becomes the transducer of a hormonal signal and
      founder of the peptide hormone receptor family, and creates the notion that
      hormone signal transduction is its sole physiological function. The third defines
      its expansion. The discovery of ROS-GC subfamily is made and it links ROS-GC with
      the physiology of phototransduction. Sections ROS-GC, a Ca(2+)-Modulated Two
      Component Transduction System to Migration Patterns and Translations of the GCAP
      Signals Into Production of Cyclic GMP are Different cover its biochemistry and
      physiology. The noteworthy events are that augmented by GCAPs, ROS-GC proves to
      be a transducer of the free Ca(2+) signals generated within neurons; ROS-GC
      becomes a two-component transduction system and establishes itself as a source of
      cyclic GMP, the second messenger of phototransduction. Section ROS-GC1 Gene
      Linked Retinal Dystrophies demonstrates how this knowledge begins to be
      translated into the diagnosis and providing the molecular definition of retinal
      dystrophies. Section Controlled By Low and High Levels of [Ca(2+)]i, ROS-GC1 is a
      Bimodal Transduction Switch discusses a striking property of ROS-GC where it
      becomes a "[Ca(2+)]i bimodal switch" and transcends its signaling role in other
      neural processes. In this course, discovery of the first CD-GCAP (Ca(2+)
      dependent guanylate cyclase activator), the S100B protein, is made. It extends
      the role of the ROS-GC transduction system beyond the phototransduction to the
      signaling processes in the synapse region between photoreceptor and cone ON
      bipolar cells; in section Ca(2+)-Modulated Neurocalcin delta ROS-GC1 Transduction
      System Exists in the Inner Plexiform Layer (IPL) of the Retinal Neurons,
      discovery of another CD-GCAP, NCdelta, is made and its linkage with signaling of
      the inner plexiform layer neurons is established. Section ROS-GC Linkage With
      Other Than Vision-Linked Neurons discusses linkage of the ROS-GC transduction
      system with other sensory transduction processes: Pineal gland, Olfaction and
      Gustation. In the next, section Evolution of a General Ca(2+)-Interlocked ROS-GC
      Signal Transduction Concept in Sensory and Sensory-Linked Neurons, a theoretical
      concept is proposed where "Ca(2+)-interlocked ROS-GC signal transduction"
      machinery becomes a common signaling component of the sensory and sensory-linked
      neurons. Closure to the review is brought by the conclusion and future
      directions. 

PMID- 25071439
TI  - Distinct molecular components for thalamic- and cortical-dependent plasticity in
      the lateral amygdala.
AB  - N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the
      lateral nucleus of the amygdala (LA) is a form of synaptic plasticity thought to
      be a cellular substrate for the extinction of fear memory. The LA receives
      converging inputs from the sensory thalamus and neocortex that are weakened
      following fear extinction. Combining field and patch-clamp electrophysiological
      recordings in mice, we show that paired-pulse low-frequency stimulation can
      induce a robust LTD at thalamic and cortical inputs to LA, and we identify
      different underlying molecular components at these pathways. We show that while
      LTD depends on NMDARs and activation of the protein phosphatases PP2B and PP1 at
      both pathways, it requires NR2B-containing NMDARs at the thalamic pathway, but
      NR2C/D-containing NMDARs at the cortical pathway. LTD appears to be induced post
      synaptically at the thalamic input but presynaptically at the cortical input,
      since post-synaptic calcium chelation and NMDAR blockade prevent thalamic but not
      cortical LTD. These results highlight distinct molecular features of LTD in LA
      that may be relevant for traumatic memory and its erasure, and for pathologies
      such as post-traumatic stress disorder (PTSD). 

PMID- 25071441
TI  - Interaction of LRRK2 with kinase and GTPase signaling cascades.
AB  - LRRK2 is a protein that interacts with a plethora of signaling molecules, but the
      complexity of LRRK2 function presents a challenge for understanding the role of
      LRRK2 in the pathophysiology of Parkinson's disease (PD). Studies of LRRK2 using
      over-expression in transgenic mice have been disappointing, however, studies
      using invertebrate systems have yielded a much clearer picture, with clear
      effects of LRRK2 expression, knockdown or deletion in Caenorhabditis elegans and
      Drosophila on modulation of survival of dopaminergic neurons. Recent studies have
      begun to focus attention on particular signaling cascades that are a target of
      LRRK2 function. LRRK2 interacts with members of the mitogen activated protein
      kinase (MAPK) pathway and might regulate the pathway action by acting as a
      scaffold that directs the location of MAPK pathway activity, without strongly
      affecting the amount of MAPK pathway activity. Binding to GTPases, GTPase
      activating proteins and GTPase exchange factors are another strong theme in LRRK2
      biology, with LRRK2 binding to rac1, cdc42, rab5, rab7L1, endoA, RGS2, ArfGAP1,
      and ArhGEF7. All of these molecules appear to feed into a function output for
      LRRK2 that modulates cytoskeletal outgrowth and vesicular dynamics, including
      autophagy. These functions likely impact modulation of alpha-synuclein
      aggregation and associated toxicity eliciting the disease processes that we term
      PD. 

PMID- 25071442
TI  - Activating transcription factor 4 (ATF4) modulates post-synaptic development and
      dendritic spine morphology.
AB  - The ubiquitously expressed activating transcription factor 4 (ATF4) has been
      variably reported to either promote or inhibit neuronal plasticity and memory.
      However, the potential cellular bases for these and other actions of ATF4 in
      brain are not well-defined. In this report, we focus on ATF4's role in post
      synaptic synapse development and dendritic spine morphology. shRNA-mediated
      silencing of ATF4 significantly reduces the densities of PSD-95 and GluR1 puncta
      (presumed markers of excitatory synapses) in long-term cultures of cortical and
      hippocampal neurons. ATF4 knockdown also decreases the density of mushroom spines
      and increases formation of abnormally-long dendritic filopodia in such cultures.
      In vivo knockdown of ATF4 in adult mouse hippocampal neurons also reduces
      mushroom spine density. In contrast, ATF4 over-expression does not affect the
      densities of PSD-95 puncta or mushrooom spines. Regulation of synaptic puncta and
      spine densities by ATF4 requires its transcriptional activity and is mediated at
      least in part by indirectly controlling the stability and expression of the total
      and active forms of the actin regulatory protein Cdc42. In support of such a
      mechanism, ATF4 silencing decreases the half-life of Cdc42 in cultured cortical
      neurons from 31.5 to 18.5 h while knockdown of Cdc42, like ATF4 knockdown,
      reduces the densities of mushroom spines and PSD-95 puncta. Thus, ATF4 appears to
      participate in neuronal development and plasticity by regulating the post
      synaptic development of synapses and dendritic mushroom spines via a mechanism
      that includes regulation of Cdc42 levels. 

PMID- 25071440
TI  - Ubiquitin pathways in neurodegenerative disease.
AB  - Control of proper protein synthesis, function, and turnover is essential for the
      health of all cells. In neurons these demands take on the additional importance
      of supporting and regulating the highly dynamic connections between neurons that
      are necessary for cognitive function, learning, and memory. Regulating multiple
      unique synaptic protein environments within a single neuron while maintaining
      cell health requires the highly regulated processes of ubiquitination and
      degradation of ubiquitinated proteins through the proteasome. In this review, we
      examine the effects of dysregulated ubiquitination and protein clearance on the
      handling of disease-associated proteins and neuronal health in the most common
      neurodegenerative diseases. 

PMID- 25071443
TI  - miR-7 and miR-153 protect neurons against MPP(+)-induced cell death via
      upregulation of mTOR pathway.
AB  - Differential expression of microRNAs (miRs) in the brain of patients with
      neurodegenerative diseases suggests that they may have key regulatory roles in
      the development of these disorders. Two such miRs, miR-7, and miR-153 have
      recently been shown to target alpha-synuclein, a protein critically involved in
      the pathological process of Parkinson's disease. By using a well-established in
      culture Parkinson's disease model that of neurotoxin 1-Methyl-4-Phenyl-Pyridinium
      (MPP(+)), we examined whether miR-7 and miR-153 display neuroprotective
      properties. Herein, we demonstrate that treatment of cortical neurons with MPP(+)
      induced a dose-dependent cell death with apoptotic characteristics. This was
      reflected in altered intracellular signaling characterized by increased levels of
      activated kinases p38MAPK and ERK1/2 and reduced levels of activated AKT, p70S6K,
      and SAPK/JNK. Overexpression of miR-7 or miR-153 by adenoviral transduction
      protected cortical neurons from MPP(+)-induced toxicity, restored neuronal
      viability and anti-apoptotic BCL-2 protein levels while attenuated activation of
      caspase-3. Moreover, both miR-7 and miR-153 interfered with MPP(+)-induced
      alterations in intracellular signaling pathways in a partially overlapping
      manner; specifically, they preserved activation of mTOR and SAPK/JNK signaling
      pathways in the MPP(+)-treated neurons, while miR-153 also attenuated MPP(+)
      induced activation of p38MAPK. No major effects were observed in the rest of
      signaling cascades or proteins investigated. Furthermore, the neuroprotective
      effect of miR-7 and miR-153 was alleviated when MPP(+) was co-administered with
      rapamycin. Taken together, our results suggest that miR-7 and miR-153 protect
      neurons from cell death by interfering with the MPP(+)-induced downregulation of
      mTOR signaling. 

PMID- 25071444
TI  - IL-4 type 1 receptor signaling up-regulates KCNN4 expression, and increases the
      KCa3.1 current and its contribution to migration of alternative-activated
      microglia.
AB  - The Ca(2+)-activated K(+) channel, KCa3.1 (KCNN4/IK1/SK4), contributes to
      "classical," pro-inflammatory activation of microglia, and KCa3.1 blockers have
      improved the outcome in several rodent models of CNS damage. For instance,
      blocking KCa3.1 with TRAM-34 rescued retinal ganglion neurons after optic nerve
      damage in vivo and, reduced p38 MAP kinase activation, production of reactive
      oxygen and nitrogen species, and neurotoxicity by microglia in vitro. In pursuing
      the therapeutic potential of KCa3.1 blockers, it is crucial to assess KCa3.1
      contributions to other microglial functions and activation states, especially the
      IL-4-induced "alternative" activation state that can counteract pro-inflammatory
      states. We recently found that IL-4 increases microglia migration - a crucial
      function in the healthy and damaged CNS - and that KCa3.1 contributes to P2Y2
      receptor-stimulated migration. Here, we discovered that KCa3.1 is greatly
      increased in alternative-activated rat microglia and then contributes to an
      enhanced migratory capacity. IL-4 up-regulated KCNN4 mRNA (by 6 h) and greatly
      increased the KCa3.1 current by 1 day, and this required de novo protein
      synthesis. The increase in current was sustained for at least 6 days. IL-4
      increased microglial migration and this was reversed by blocking KCa3.1 with TRAM
      34. A panel of inhibitors of signal-transduction mediators was used to analyze
      contributions of IL-4-related signaling pathways. Induction of KCNN4 mRNA and
      KCa3.1 current was mediated specifically through IL-4 binding to the type I
      receptor and, surprisingly, it required JAK3, Ras/MEK/ERK signaling and the
      transcription factor, activator protein-1, rather than JAK2, STAT6, or
      phosphatidylinositol 3-kinase.The same receptor subtype and pathway were required
      for the enhanced KCa3.1-dependent migration. In providing the first direct
      signaling link between an IL-4 receptor, expression and roles of an ion channel,
      this study also highlights the potential importance of KCa3.1 in alternative
      activated microglia. 

PMID- 25071445
TI  - Dysfunctional mitochondrial Ca(2+) handling in mutant SOD1 mouse models of fALS:
      integration of findings from motor neuron somata and motor terminals.
AB  - Abundant evidence indicates that mitochondrial dysfunction and Ca(2+)
      dysregulation contribute to the muscle denervation and motor neuron death that
      occur in mouse models of familial amyotrophic lateral sclerosis (fALS). This
      perspective considers measurements of mitochondrial function and Ca(2+) handling
      made in both motor neuron somata and motor nerve terminals of SOD1-G93A mice at
      different disease stages. These complementary studies are integrated into a model
      of how mitochondrial dysfunction disrupts handling of stimulation-induced Ca(2+)
      loads in presymptomatic and end-stages of this disease. Also considered are
      possible mechanisms underlying the findings that some treatments that preserve
      motor neuron somata fail to postpone degeneration of motor axons and terminals. 

PMID- 25071447
TI  - Chemokine receptor expression by inflammatory T cells in EAE.
AB  - Chemokines direct cellular infiltration to tissues, and their receptors and
      signaling pathways represent targets for therapy in diseases such as multiple
      sclerosis (MS). The chemokine CCL20 is expressed in choroid plexus, a site of
      entry of T cells to the central nervous system (CNS). The CCL20 receptor CCR6 has
      been reported to be selectively expressed by CD4(+) T cells that produce the
      cytokine IL-17 (Th17 cells). Th17 cells and interferon-gamma (IFNgamma)-producing
      Th1 cells are implicated in induction of MS and its animal model experimental
      autoimmune encephalomyelitis (EAE). We have assessed whether CCR6 identifies
      specific inflammatory T cell subsets in EAE. Our approach was to induce EAE, and
      then examine chemokine receptor expression by cytokine-producing T cells sorted
      from CNS at peak disease. About 7% of CNS-infiltrating CD4(+) T cells produced
      IFNgamma in flow cytometric cytokine assays, whereas less than 1% produced IL-17.
      About 1% of CD4(+) T cells produced both cytokines. CCR6 was expressed by Th1,
      Th1+17 and by Th17 cells, but not by CD8(+) T cells. CD8(+) T cells expressed
      CXCR3, which was also expressed by CD4(+) T cells, with no correlation to
      cytokine profile. Messenger RNA for IFNgamma, IL-17A, and the Th1 and Th17
      associated transcription factors T-bet and RORgammat was detected in both CCR6(+)
      and CXCR3(+) CD4(+) T cells. IFNgamma, but not IL-17A mRNA expression was
      detected in CD8(+) T cells in CNS. CCR6 and CD4 were co-localized in spinal cord
      infiltrates by double immunofluorescence. Consistent with flow cytometry data
      some but not all CD4(+) T cells expressed CCR6 within infiltrates. CD4-negative
      CCR6(+) cells included macrophage/microglial cells. Thus we have for the first
      time directly studied CD4(+) and CD8(+) T cells in the CNS of mice with peak EAE,
      and determined IFNgamma and IL17 expression by cells expressing CCR6 and CXCR3.
      We show that neither CCR6 or CXCR3 align with CD4 T cell subsets, and Th1 or
      mixed Th1+17 predominate in EAE. 

PMID- 25071446
TI  - Kir3 channel signaling complexes: focus on opioid receptor signaling.
AB  - Opioids are among the most effective drugs to treat severe pain. They produce
      their analgesic actions by specifically activating opioid receptors located along
      the pain perception pathway where they inhibit the flow of nociceptive
      information. This inhibition is partly accomplished by activation of
      hyperpolarizing G protein-coupled inwardly-rectifying potassium (GIRK or Kir3)
      channels. Kir3 channels control cellular excitability in the central nervous
      system and in the heart and, because of their ubiquitous distribution, they
      mediate the effects of a large range of hormones and neurotransmitters which,
      upon activation of corresponding G protein-coupled receptors (GPCRs) lead to
      channel opening. Here we analyze GPCR signaling via these effectors in reference
      to precoupling and collision models. Existing knowledge on signaling bias is
      discussed in relation to these models as a means of developing strategies to
      produce novel opioid analgesics with an improved side effects profile. 

PMID- 25071448
TI  - Neurogenin 3 mediates sex chromosome effects on the generation of sex differences
      in hypothalamic neuronal development.
AB  - The organizational action of testosterone during critical periods of development
      is the cause of numerous sex differences in the brain. However, sex differences
      in neuritogenesis have been detected in primary neuronal hypothalamic cultures
      prepared before the peak of testosterone production by fetal testis. In the
      present study we assessed the hypothesis of that cell-autonomous action of sex
      chromosomes can differentially regulate the expression of the neuritogenic gene
      neurogenin 3 (Ngn3) in male and female hypothalamic neurons, generating sex
      differences in neuronal development. Neuronal cultures were prepared from male
      and female E14 mouse hypothalami, before the fetal peak of testosterone. Female
      neurons showed enhanced neuritogenesis and higher expression of Ngn3 than male
      neurons. The silencing of Ngn3 abolished sex differences in neuritogenesis,
      decreasing the differentiation of female neurons. The sex difference in Ngn3
      expression was determined by sex chromosomes, as demonstrated using the four core
      genotypes mouse model, in which a spontaneous deletion of the testis-determining
      gene Sry from the Y chromosome was combined with the insertion of the Sry gene
      onto an autosome. In addition, the expression of Ngn3, which is also known to
      mediate the neuritogenic actions of estradiol, was increased in the cultures
      treated with the hormone, but only in those from male embryos. Furthermore, the
      hormone reversed the sex differences in neuritogenesis promoting the
      differentiation of male neurons. These findings indicate that Ngn3 mediates both
      cell-autonomous actions of sex chromosomes and hormonal effects on
      neuritogenesis. 

PMID- 25071449
TI  - DISC1 knockdown impairs the tangential migration of cortical interneurons by
      affecting the actin cytoskeleton.
AB  - Disrupted-in-Schizophrenia 1 (DISC1) is a risk gene for a spectrum of major
      mental disorders. It has been shown to regulate radial migration as well as
      dendritic arborization during neurodevelopment and corticogenesis. In a previous
      study we demonstrated through in vitro experiments that DISC1 also controls the
      tangential migration of cortical interneurons originating from the medial
      ganglionic eminence (MGE). Here we first show that DISC1 is necessary for the
      proper tangential migration of cortical interneurons in the intact brain.
      Expression of EGFP under the Lhx6 promotor allowed us to analyze exclusively
      interneurons transfected in the MGE after in utero electroporation. After 3 days
      in utero, DISC1 deficient interneurons displayed prolonged leading processes and,
      compared to control, fewer neurons reached the cortex. Time-lapse video
      microscopy of cortical feeder-layers revealed a decreased migration velocity due
      to a reduction of soma translocations. Immunostainings indicated that DISC1 is co
      localized with F-actin in the growth cone-like structure of the leading process.
      DISC1 knockdown reduced F-actin levels whereas the overall actin level was not
      altered. Moreover, DISC1 knockdown also decreased levels of phosphorylated
      Girdin, which cross-links F-actin, as well as the Girdin-activator pAkt. In
      contrast, using time-lapse video microscopy of fluorescence-tagged tubulin and
      EB3 in fibroblasts, we found no effects on microtubule polymerization when DISC1
      was reduced. However, DISC1 affected the acetylation of microtubules in the
      leading processes of MGE-derived cortical interneurons. Together, our results
      provide a mechanism how DISC1 might contribute to interneuron migration thereby
      explaining the reduced number of specific classes of cortical interneurons in
      some DISC1 mouse models. 

PMID- 25071450
TI  - J protein mutations and resulting proteostasis collapse.
AB  - Despite a century of intensive investigation the effective treatment of protein
      aggregation diseases remains elusive. Ordinarily, molecular chaperones ensure
      that proteins maintain their functional conformation. The appearance of misfolded
      proteins that aggregate implies the collapse of the cellular chaperone quality
      control network. That said, the cellular chaperone network is extensive and
      functional information regarding the detailed action of specific chaperones is
      not yet available. J proteins (DnaJ/Hsp40) are a family of chaperone cofactors
      that harness Hsc70 (heat shock cognate protein of 70 kDa) for diverse
      conformational cellular tasks and, as such, represent novel clinically relevant
      targets for diseases resulting from the disruption of proteostasis. Here we
      review incisive reports identifying mutations in individual J protein chaperones
      and the proteostasis collapse that ensues. 

PMID- 25071451
TI  - Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons,
      microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death.
AB  - Upon noxious insults, cells of the brain parenchyma activate endogenous self
      protective mechanisms to counteract brain damage. Interplay between microglia and
      astrocytes can be determinant to build a physiological response to noxious
      stimuli arisen from injury or stress, thus understanding the cross talk between
      microglia and astrocytes would be helpful to elucidate the role of glial cells in
      endogenous protective mechanisms and might contribute to the development of new
      strategy to mobilize such program and reduce brain cell death. Here we
      demonstrate that chemokines CX3CL1 and CXCL16 are molecular players that
      synergistically drive cross-talk between neurons, microglia and astrocytes to
      promote physiological neuroprotective mechanisms that counteract neuronal cell
      death due to ischemic and excitotoxic insults. In an in vivo model of permanent
      middle cerebral artery occlusion (pMCAO) we found that exogenous administration
      of soluble CXCL16 reduces ischemic volume and that, upon pMCAO, endogenous CXCL16
      signaling restrains brain damage, being ischemic volume reduced in mice that lack
      CXCL16 receptor. We demonstrated that CX3CL1, acting on microglia, elicits CXCL16
      release from glia and this is important to induce neroprotection since lack of
      CXCL16 signaling impairs CX3CL1 neuroprotection against both in vitro Glu
      excitotoxic insult and pMCAO. Moreover the activity of adenosine receptor A3R and
      the astrocytic release of CCL2 play also a role in trasmembrane chemokine
      neuroprotective effect, since their inactivation reduces CX3CL1- and CXCL16
      induced neuroprotection. 

PMID- 25071452
TI  - Synaptic dynamics contribute to long-term single neuron response fluctuations.
AB  - Firing rate variability at the single neuron level is characterized by long
      memory processes and complex statistics over a wide range of time scales (from
      milliseconds up to several hours). Here, we focus on the contribution of non
      stationary efficacy of the ensemble of synapses-activated in response to a given
      stimulus-on single neuron response variability. We present and validate a method
      tailored for controlled and specific long-term activation of a single cortical
      neuron in vitro via synaptic or antidromic stimulation, enabling a clear
      separation between two determinants of neuronal response variability: membrane
      excitability dynamics vs. synaptic dynamics. Applying this method we show that,
      within the range of physiological activation frequencies, the synaptic ensemble
      of a given neuron is a key contributor to the neuronal response variability, long
      memory processes and complex statistics observed over extended time scales.
      Synaptic transmission dynamics impact on response variability in stimulation
      rates that are substantially lower compared to stimulation rates that drive
      excitability resources to fluctuate. Implications to network embedded neurons are
      discussed. 

PMID- 25071453
TI  - Effects of dopamine on response properties of ON-OFF RGCs in encoding stimulus
      durations.
AB  - Single retinal ganglion cell's (RGCs) response properties, such as spike count
      and response latency, are known to encode some features of visual stimuli. On the
      other hand, neuronal response can be modulated by dopamine (DA), an important
      endogenous neuromodulator in the retina. In the present study, we investigated
      the effects of DA on the spike count and the response latency of bullfrog ON-OFF
      RGCs during exposure to different stimulus durations. We found that neuronal
      spike count and response latency were both changed with stimulus durations, and
      exogenous DA (10 MUM) obviously attenuated the stimulus-duration-dependent
      response latency change. Information analysis showed that the information about
      light ON duration was mainly carried by the OFF response and vice versa, and the
      stimulation information was carried by both spike count and response latency.
      However, during DA application, the information carried by the response latency
      was greatly decreased, which suggests that dopaminergic pathway is involved in
      modulating the role of response latency in encoding the information about
      stimulus durations. 

PMID- 25071455
TI  - Deep layer neurons in the rat medial entorhinal cortex fire sparsely irrespective
      of spatial novelty.
AB  - Extracellular recordings in medial entorhinal cortex have revealed the existence
      of spatially-modulated firing patterns, which are thought to contribute to a
      cognitive map of external space. Previous work indicated that during exploration
      of novel environments, spiking activity in deep entorhinal layers is much sparser
      than in superficial layers. In the present report, we ask whether this laminar
      activity profile is a consequence of environmental novelty. We report on a large
      dataset of juxtacellularly-recorded neurons (n = 70) whose spiking activity was
      monitored while rats explored either a novel or a familiar environment, or both
      within the same session. Irrespective of previous knowledge of the environment,
      deep layer activity was very low during exploration (median firing rate 0.4 Hz
      for non-silent cells), with a large fraction of silent cells (n = 19 of a total
      37), while superficial layer activity was several times higher (median firing
      rate 2.4 Hz; n = 33). The persistence of laminar differences in firing activity
      both under environmental novelty and familiarity, and even in head-restrained
      stationary animals, suggests that sparse coding might be a constitutive feature
      of deep entorhinal layers. 

PMID- 25071454
TI  - Functional imaging of cortical feedback projections to the olfactory bulb.
AB  - Processing of sensory information is substantially shaped by centrifugal, or
      feedback, projections from higher cortical areas, yet the functional properties
      of these projections are poorly characterized. Here, we used genetically-encoded
      calcium sensors (GCaMPs) to functionally image activation of centrifugal
      projections targeting the olfactory bulb (OB). The OB receives massive
      centrifugal input from cortical areas but there has been as yet no
      characterization of their activity in vivo. We focused on projections to the OB
      from the anterior olfactory nucleus (AON), a major source of cortical feedback to
      the OB. We expressed GCaMP selectively in AON projection neurons using a mouse
      line expressing Cre recombinase (Cre) in these neurons and Cre-dependent viral
      vectors injected into AON, allowing us to image GCaMP fluorescence signals from
      their axon terminals in the OB. Electrical stimulation of AON evoked large
      fluorescence signals that could be imaged from the dorsal OB surface in vivo.
      Surprisingly, odorants also evoked large signals that were transient and coupled
      to odorant inhalation both in the anesthetized and awake mouse, suggesting that
      feedback from AON to the OB is rapid and robust across different brain states.
      The strength of AON feedback signals increased during wakefulness, suggesting a
      state-dependent modulation of cortical feedback to the OB. Two-photon GCaMP
      imaging revealed that different odorants activated different subsets of
      centrifugal AON axons and could elicit both excitation and suppression in
      different axons, indicating a surprising richness in the representation of odor
      information by cortical feedback to the OB. Finally, we found that activating
      neuromodulatory centers such as basal forebrain drove AON inputs to the OB
      independent of odorant stimulation. Our results point to the AON as a
      multifunctional cortical area that provides ongoing feedback to the OB and also
      serves as a descending relay for other neuromodulatory systems. 

PMID- 25071456
TI  - Frequency transformation in the auditory lemniscal thalamocortical system.
AB  - The auditory lemniscal thalamocortical (TC) pathway conveys information from the
      ventral division of the medial geniculate body to the primary auditory cortex
      (A1). Although their general topographic organization has been well
      characterized, functional transformations at the lemniscal TC synapse still
      remain incompletely codified, largely due to the need for integration of
      functional anatomical results with the variability observed with various animal
      models and experimental techniques. In this review, we discuss these issues with
      classical approaches, such as in vivo extracellular recordings and tracer
      injections to physiologically identified areas in A1, and then compare these
      studies with modern approaches, such as in vivo two-photon calcium imaging, in
      vivo whole-cell recordings, optogenetic methods, and in vitro methods using slice
      preparations. A surprising finding from a comparison of classical and modern
      approaches is the similar degree of convergence from thalamic neurons to single
      A1 neurons and clusters of A1 neurons, although, thalamic convergence to single
      A1 neurons is more restricted from areas within putative thalamic frequency
      lamina. These comparisons suggest that frequency convergence from thalamic input
      to A1 is functionally limited. Finally, we consider synaptic organization of TC
      projections and future directions for research. 

PMID- 25071457
TI  - Anatomical characterization of Cre driver mice for neural circuit mapping and
      manipulation.
AB  - Significant advances in circuit-level analyses of the brain require tools that
      allow for labeling, modulation of gene expression, and monitoring and
      manipulation of cellular activity in specific cell types and/or anatomical
      regions. Large-scale projects and individual laboratories have produced hundreds
      of gene-specific promoter-driven Cre mouse lines invaluable for enabling genetic
      access to subpopulations of cells in the brain. However, the potential utility of
      each line may not be fully realized without systematic whole brain
      characterization of transgene expression patterns. We established a high
      throughput in situ hybridization (ISH), imaging and data processing pipeline to
      describe whole brain gene expression patterns in Cre driver mice. Currently,
      anatomical data from over 100 Cre driver lines are publicly available via the
      Allen Institute's Transgenic Characterization database, which can be used to
      assist researchers in choosing the appropriate Cre drivers for functional,
      molecular, or connectional studies of different regions and/or cell types in the
      brain. 

PMID- 25071458
TI  - Monoaminergic control of spinal locomotor networks in SOD1G93A newborn mice.
AB  - Mutations in the gene that encodes Cu/Zn-superoxide dismutase (SOD1) are the
      cause of approximately 20% of familial forms of amyotrophic lateral sclerosis
      (ALS), a fatal neurodegenerative disease characterized by the progressive loss of
      motor neurons. While ALS symptoms appear in adulthood, spinal motoneurons exhibit
      functional alterations as early as the embryonic and postnatal stages in the
      murine model of ALS, the SOD1 mice. Monoaminergic - i.e., dopaminergic (DA),
      serotoninergic (5-HT), and noradrenergic (NA) - pathways powerfully control
      spinal networks and contribute significantly to their embryonic and postnatal
      maturation. Alterations in monoaminergic neuromodulation during development could
      therefore lead to impairments in the motoneuronal physiology. In this study, we
      sought to determine whether the monoaminergic spinal systems are modified in the
      early stages of development in SOD1 mice. Using a post-mortem analysis by high
      performance liquid chromatography (HPLC), monoaminergic neuromodulators and their
      metabolites were quantified in the lumbar spinal cord of SOD1 and wild-type (WT)
      mice aged one postnatal day (P1) and P10. This analysis underscores an increased
      content of DA in the SOD1 lumbar spinal cord compared to that of WT mice but
      failed to reveal any modification of the other monoaminergic contents. In a next
      step, we compared the efficiency of the monoaminergic compounds in triggering and
      modulating fictive locomotion in WT and SOD1 mice. This study was performed in P1
      P3 SOD1 mice and age-matched control littermates using extracellular recordings
      from the lumbar ventral roots in the in vitro isolated spinal cord preparation.
      This analysis revealed that the spinal networks of SOD1(G93A) mice could generate
      normal locomotor activity in the presence of NMA-5-HT. Interestingly, we also
      observed that SOD1 spinal networks have an increased sensitivity to NA compared
      to WT spinal circuits but exhibited similar DA responses. 

PMID- 25071459
TI  - Cell-type specific short-term plasticity at auditory nerve synapses controls feed
      forward inhibition in the dorsal cochlear nucleus.
AB  - Feed-forward inhibition (FFI) represents a powerful mechanism by which control of
      the timing and fidelity of action potentials in local synaptic circuits of
      various brain regions is achieved. In the cochlear nucleus, the auditory nerve
      provides excitation to both principal neurons and inhibitory interneurons. Here,
      we investigated the synaptic circuit associated with fusiform cells (FCs),
      principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation
      from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on
      their basal dendrites in the deep layer of DCN. Despite the importance of these
      inputs in regulating fusiform cell firing behavior, the mechanisms determining
      the balance of excitation and FFI in this circuit are not well understood.
      Therefore, we examined the timing and plasticity of auditory nerve driven FFI
      onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI
      had the same stimulation thresholds indicating they could be triggered by
      activation of the same fibers. In other FCs, excitation and inhibition exhibit
      different stimulus thresholds, suggesting FCs and TVCs might be activated by
      different sets of fibers. In addition, we find that during repetitive activation,
      synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of
      short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in
      FCs exhibit short-term depression because of prominent synaptic depression at the
      auditory nerve-TVC synapse. Depression of this feedforward inhibitory input
      causes a shift in the balance of fusiform cell synaptic input towards greater
      excitation and suggests that fusiform cell spike output will be enhanced by
      physiological patterns of auditory nerve activity. 

PMID- 25071461
TI  - Inter- and intralimb adaptations to a sensory perturbation during activation of
      the serotonin system after a low spinal cord transection in neonatal rats.
AB  - Activation of the serotonin system has been shown to induce locomotor activity
      following a spinal cord transection. This study examines how the isolated spinal
      cord adapts to a sensory perturbation during activation of the serotonergic
      system. Real-time and persistent effects of a perturbation were examined in
      intact and spinal transected newborn rats. Rats received a spinal surgery (sham
      or low thoracic transection) on postnatal day 1 and were tested 9 days later. At
      test, subjects were treated with the serotonergic receptor agonist quipazine (3.0
      mg/kg) to induce stepping behavior. Half of the subjects experienced range of
      motion (ROM) restriction during stepping, while the other half did not.
      Differences in stepping behavior (interlimb coordination) and limb trajectories
      (intralimb coordination) were found to occur in both intact and spinal subjects.
      Adaptations were seen in the forelimbs and hindlimbs. Also, real-time and
      persistent effects of ROM restriction (following removal of the perturbation)
      were seen in ROM-restricted subjects. This study demonstrates the sensitivity of
      the isolated spinal cord to sensory feedback in conjunction with serotonin
      modulation. 

PMID- 25071462
TI  - Unraveling Cajal's view of the olfactory system.
AB  - The olfactory system has a highly regular organization of interconnected synaptic
      circuits from the periphery. It is therefore an excellent model for understanding
      general principles about how the brain processes information. Cajal revealed the
      basic cell types and their interconnections at the end of the XIX century. Since
      his original descriptions, the observation and analysis of the olfactory system
      and its components represents a major topic in neuroscience studies, providing
      important insights into the neural mechanisms. In this review, we will highlight
      the importance of Cajal contributions and his legacy to the actual knowledge of
      the olfactory system. 

PMID- 25071463
TI  - Epilog: Cajal's unique and legitimated school.
AB  - Santiago Ramon y Cajal is recognized as the founder of modern neuroscience, his
      discoveries representing the fundamental pillars of our current understanding of
      the nervous system. As Cajal's career spanned a critical period in Spanish
      history, he witnessed strong social demands for progress in culture, education,
      and science. Indeed, the life of Santiago Ramon y Cajal can be considered to
      reflect the gradual development of Spanish science from the last third of the
      19th century. Cajal promoted a national movement that had important consequences
      for Spanish science, mainly triggered by the creation of the "Junta para
      Ampliacion de Estudios e Investigaciones Cientificas," an instrument he
      established to enrich scientific research and that was later to bear such
      abundant fruit. The school generated by Cajal profited from this development,
      through which all Cajal's disciples received fellowships to train in laboratories
      across Europe. Unfortunately, the Spanish Civil War disrupted this revitalization
      of Spanish science and provoked the diaspora of many Spanish scientists. However,
      a political impulse, mostly following this spirit, was resumed in Spain during
      the eighties that successfully led to a renaissance in Spanish science. 

PMID- 25071460
TI  - Mapping arealisation of the visual cortex of non-primate species: lessons for
      development and evolution.
AB  - The integration of the visual stimulus takes place at the level of the neocortex,
      organized in anatomically distinct and functionally unique areas. Primates,
      including humans, are heavily dependent on vision, with approximately 50% of
      their neocortical surface dedicated to visual processing and possess many more
      visual areas than any other mammal, making them the model of choice to study
      visual cortical arealisation. However, in order to identify the mechanisms
      responsible for patterning the developing neocortex, specifying area identity as
      well as elucidate events that have enabled the evolution of the complex primate
      visual cortex, it is essential to gain access to the cortical maps of alternative
      species. To this end, species including the mouse have driven the identification
      of cellular markers, which possess an area-specific expression profile, the
      development of new tools to label connections and technological advance in
      imaging techniques enabling monitoring of cortical activity in a behaving animal.
      In this review we present non-primate species that have contributed to
      elucidating the evolution and development of the visual cortex. We describe the
      current understanding of the mechanisms supporting the establishment of areal
      borders during development, mainly gained in the mouse thanks to the availability
      of genetically modified lines but also the limitations of the mouse model and the
      need for alternate species. 

PMID- 25071466
TI  - Great insight created by tiny holes; celebrating 40 years of brain micropunch
      technique.

PMID- 25071464
TI  - Combinatorial expression of Lef1, Lhx2, Lhx5, Lhx9, Lmo3, Lmo4, and Prox1 helps
      to identify comparable subdivisions in the developing hippocampal formation of
      mouse and chicken.
AB  - We carried out a study of the expression patterns of seven developmental
      regulatory genes (Lef1, Lhx2, Lhx9, Lhx5, Lmo3, Lmo4, and Prox1), in combination
      with topological position, to identify the medial pallial derivatives, define its
      major subdivisions, and compare them between mouse and chicken. In both species,
      the medial pallium is defined as a pallial sector adjacent to the cortical hem
      and roof plate/choroid tela, showing moderate to strong ventricular zone
      expression of Lef1, Lhx2, and Lhx9, but not Lhx5. Based on this, the hippocampal
      formation (indusium griseum, dentate gyrus, Ammon's horn fields, and subiculum),
      the medial entorhinal cortex, and part of the amygdalo-hippocampal transition
      area of mouse appeared to derive from the medial pallium. In the chicken, based
      on the same position and gene expression profile, we propose that the hippocampus
      (including the V-shaped area), the parahippocampal area (including its
      caudolateral part), the entorhinal cortex, and the amygdalo-hippocampal
      transition area are medial pallial derivatives. Moreover, the combinatorial
      expression of Lef1, Prox1, Lmo4, and Lmo3 allowed the identification of dentate
      gyrus/CA3-like, CA1/subicular-like, and medial entorhinal-like comparable sectors
      in mouse and chicken, and point to the existence of mostly conserved molecular
      networks involved in hippocampal complex development. Notably, while the mouse
      medial entorhinal cortex derives from the medial pallium (similarly to the
      hippocampal formation, both being involved in spatial navigation and spatial
      memory), the lateral entorhinal cortex (involved in processing non-spatial,
      contextual information) appears to derive from a distinct dorsolateral caudal
      pallial sector. 

PMID- 25071465
TI  - Characterization of excitatory and inhibitory neuron activation in the mouse
      medial prefrontal cortex following palatable food ingestion and food driven
      exploratory behavior.
AB  - The medial prefrontal cortex (mPFC) is implicated in aspects of executive
      function, that include the modulation of attentional and memory processes
      involved in goal selection. Food-seeking behavior has been shown to involve
      activation of the mPFC, both during the execution of strategies designed to
      obtain food and during the consumption of food itself. As these behaviors likely
      require differential engagement of the prefrontal cortex, we hypothesized that
      the pattern of neuronal activation would also be behavior dependent. In this
      study we describe, for the first time, the expression of Fos in different layers
      and cell types of the infralimbic/dorsal peduncular and prelimbic/anterior
      cingulate subdivisions of mouse mPFC following both the consumption of palatable
      food and following exploratory activity of the animal directed at obtaining food
      reward. While both manipulations led to increases of Fos expression in principal
      excitatory neurons relative to control, food-directed exploratory activity
      produced a significantly greater increase in Fos expression than observed in the
      food intake condition. Consequently, we hypothesized that mPFC interneuron
      activation would also be differentially engaged by these manipulations.
      Interestingly, Fos expression patterns differed substantially between treatments
      and interneuron subtype, illustrating how the differential engagement of subsets
      of mPFC interneurons depends on the behavioral state. In our experiments, both
      vasoactive intestinal peptide- and parvalbumin-expressing neurons showed enhanced
      Fos expression only during the food-dependent exploratory task and not during
      food intake. Conversely, elevations in arcuate and paraventricular hypothalamic
      fos expression were only observed following food intake and not following food
      driven exploration. Our data suggest that select activation of these cell types
      may be required to support high cognitive demand states such as observed during
      exploration while being dispensable during the ingestion of freely available
      food. 

PMID- 25071467
TI  - Are the mechanisms driving somatosensory reorganization cortical or subcortical?

PMID- 25071468
TI  - Anatomy, histochemistry, and immunohistochemistry of the olfactory subsystems in
      mice.
AB  - The four regions of the murine nasal cavity featuring olfactory neurons were
      studied anatomically and by labeling with lectins and relevant antibodies with a
      view to establishing criteria for the identification of olfactory subsystems that
      are readily applicable to other mammals. In the main olfactory epithelium and the
      septal organ the olfactory sensory neurons (OSNs) are embedded in quasi
      stratified columnar epithelium; vomeronasal OSNs are embedded in epithelium
      lining the medial interior wall of the vomeronasal duct and do not make contact
      with the mucosa of the main nasal cavity; and in Gruneberg's ganglion a small
      isolated population of OSNs lies adjacent to, but not within, the epithelium.
      With the exception of Gruneberg's ganglion, all the tissues expressing olfactory
      marker protein (OMP) (the above four nasal territories, the vomeronasal and main
      olfactory nerves, and the main and accessory olfactory bulbs) are also labeled by
      Lycopersicum esculentum agglutinin, while Ulex europaeus agglutinin I labels all
      and only tissues expressing Galphai2 (the apical sensory neurons of the
      vomeronasal organ, their axons, and their glomerular destinations in the anterior
      accessory olfactory bulb). These staining patterns of UEA-I and LEA may
      facilitate the characterization of olfactory anatomy in other species. A 710
      section atlas of the anatomy of the murine nasal cavity has been made available
      on line. 

PMID- 25071469
TI  - Endoplasmic reticulum calcium stores in dendritic spines.
AB  - Despite decades of research, the role of calcium stores in dendritic spines
      structure, function and plasticity is still debated. The reasons for this may
      have to do with the multitude of overlapping calcium handling machineries in the
      neuron, including stores, voltage and ligand gated channels, pumps and
      transporters. Also, different cells in the brain are endowed with calcium stores
      that are activated by different receptor types, and their differential
      compartmentalization in dendrites, spines and presynaptic terminals complicates
      their analysis. In the present review we address several key issues, including
      the role of calcium stores in synaptic plasticity, their role during development,
      in stress and in neurodegenerative diseases. Apparently, there is increasing
      evidence for a crucial role of calcium stores, especially of the ryanodine
      species, in synaptic plasticity and neuronal survival. 

PMID- 25071470
TI  - A comparison of manual neuronal reconstruction from biocytin histology or 2
      photon imaging: morphometry and computer modeling.
AB  - Accurate 3D reconstruction of neurons is vital for applications linking anatomy
      and physiology. Reconstructions are typically created using Neurolucida after
      biocytin histology (BH). An alternative inexpensive and fast method is to use
      freeware such as Neuromantic to reconstruct from fluorescence imaging (FI) stacks
      acquired using 2-photon laser-scanning microscopy during physiological recording.
      We compare these two methods with respect to morphometry, cell classification,
      and multicompartmental modeling in the NEURON simulation environment.
      Quantitative morphological analysis of the same cells reconstructed using both
      methods reveals that whilst biocytin reconstructions facilitate tracing of more
      distal collaterals, both methods are comparable in representing the overall
      morphology: automated clustering of reconstructions from both methods
      successfully separates neocortical basket cells from pyramidal cells but not BH
      from FI reconstructions. BH reconstructions suffer more from tissue shrinkage and
      compression artifacts than FI reconstructions do. FI reconstructions, on the
      other hand, consistently have larger process diameters. Consequently, significant
      differences in NEURON modeling of excitatory post-synaptic potential (EPSP)
      forward propagation are seen between the two methods, with FI reconstructions
      exhibiting smaller depolarizations. Simulated action potential backpropagation
      (bAP), however, is indistinguishable between reconstructions obtained with the
      two methods. In our hands, BH reconstructions are necessary for NEURON modeling
      and detailed morphological tracing, and thus remain state of the art, although
      they are more labor intensive, more expensive, and suffer from a higher failure
      rate due to the occasional poor outcome of histological processing. However, for
      a subset of anatomical applications such as cell type identification, FI
      reconstructions are superior, because of indistinguishable classification
      performance with greater ease of use, essentially 100% success rate, and lower
      cost. 

PMID- 25071471
TI  - Brain renin-angiotensin system and dopaminergic cell vulnerability.
AB  - Although the renin-angiotensin system (RAS) was classically considered as a
      circulating system that regulates blood pressure, many tissues are now known to
      have a local RAS. Angiotensin, via type 1 receptors, is a major activator of the
      NADPH-oxidase complex, which mediates several key events in oxidative stress (OS)
      and inflammatory processes involved in the pathogenesis of major aging-related
      diseases. Several studies have demonstrated the presence of RAS components in the
      basal ganglia, and particularly in the nigrostriatal system. In the nigrostriatal
      system, RAS hyperactivation, via NADPH-oxidase complex activation, exacerbates OS
      and the microglial inflammatory response and contributes to progression of
      dopaminergic degeneration, which is inhibited by angiotensin receptor blockers
      and angiotensin converting enzyme (ACE) inhibitors. Several factors may induce an
      increase in RAS activity in the dopaminergic system. A decrease in dopaminergic
      activity induces compensatory upregulation of local RAS function in both
      dopaminergic neurons and glia. In addition to its role as an essential
      neurotransmitter, dopamine may also modulate microglial inflammatory responses
      and neuronal OS via RAS. Important counterregulatory interactions between
      angiotensin and dopamine have also been observed in several peripheral tissues.
      Neurotoxins and proinflammatory factors may also act on astrocytes to induce an
      increase in RAS activity, either independently of or before the loss of dopamine.
      Consistent with a major role of RAS in dopaminergic vulnerability, increased RAS
      activity has been observed in the nigra of animal models of aging, menopause and
      chronic cerebral hypoperfusion, which also showed higher dopaminergic
      vulnerability. Manipulation of the brain RAS may constitute an effective
      neuroprotective strategy against dopaminergic vulnerability and progression of
      Parkinson's disease. 

PMID- 25071473
TI  - Electroencephalographic effects of ketamine on power, cross-frequency coupling,
      and connectivity in the alpha bandwidth.
AB  - Recent studies of propofol-induced unconsciousness have identified characteristic
      properties of electroencephalographic alpha rhythms that may be mediated by drug
      activity at gamma-aminobutyric acid (GABA) receptors in the thalamus. However,
      the effect of ketamine (a primarily non-GABAergic anesthetic drug) on alpha
      oscillations has not been systematically evaluated. We analyzed the
      electroencephalogram of 28 surgical patients during consciousness and ketamine
      induced unconsciousness with a focus on frontal power, frontal cross-frequency
      coupling, frontal-parietal functional connectivity (measured by coherence and
      phase lag index), and frontal-to-parietal directional connectivity (measured by
      directed phase lag index) in the alpha bandwidth. Unlike past studies of
      propofol, ketamine-induced unconsciousness was not associated with increases in
      the power of frontal alpha rhythms, characteristic cross-frequency coupling
      patterns of frontal alpha power and slow-oscillation phase, or decreases in
      coherence in the alpha bandwidth. Like past studies of propofol using undirected
      and directed phase lag index, ketamine reduced frontal-parietal (functional) and
      frontal-to-parietal (directional) connectivity in the alpha bandwidth. These
      results suggest that directional connectivity changes in the alpha bandwidth may
      be state-related markers of unconsciousness induced by both GABAergic and non
      GABAergic anesthetics. 

PMID- 25071474
TI  - Comparative organization of the claustrum: what does structure tell us about
      function?
AB  - The claustrum is a subcortical nucleus present in all placental mammals. Many
      anatomical studies have shown that its inputs are predominantly from the cerebral
      cortex and its outputs are back to the cortex. This connectivity thus suggests
      that the claustrum serves to amplify or facilitate information processing in the
      cerebral cortex. The size and the complexity of the cerebral cortex varies
      dramatically across species. Some species have lissencephalic brains, with few
      cortical areas, while others have a greatly expanded cortex and many cortical
      areas. This evolutionary diversity in the cerebral cortex raises several
      questions about the claustrum. Does its volume expand in coordination with the
      expansion of cortex and does it acquire new functions related to the new cortical
      functions? Here we survey the organization of the claustrum in animals with large
      brains, including great apes and cetaceans. Our data suggest that the claustrum
      is not always a continuous structure. In monkeys and gorillas there are a few
      isolated islands of cells near the main body of the nucleus. In cetaceans,
      however, there are many isolated cell islands. These data suggest constraints on
      the possible function of the claustrum. Some authors propose that the claustrum
      has a more global role in perception or consciousness that requires
      intraclaustral integration of information. These theories postulate mechanisms
      like gap junctions between claustral cells or a "syncytium" to mediate
      intraclaustral processing. The presence of discontinuities in the structure of
      the claustrum, present but minimal in some primates, but dramatically clear in
      cetaceans, argues against the proposed mechanisms of intraclaustral processing of
      information. The best interpretation of function, then, is that each functional
      subdivision of the claustrum simply contributes to the function of its cortical
      partner. 

PMID- 25071472
TI  - Matrix metalloproteinase-9 involvement in the structural plasticity of dendritic
      spines.
AB  - Dendritic spines are the locus for excitatory synaptic transmission in the brain
      and thus play a major role in neuronal plasticity. The ability to alter synaptic
      connections includes volumetric changes in dendritic spines that are driven by
      scaffolds created by the extracellular matrix (ECM). Here, we review the effects
      of the proteolytic activity of ECM proteases in physiological and pathological
      structural plasticity. We use matrix metalloproteinase-9 (MMP-9) as an example of
      an ECM modifier that has recently emerged as a key molecule in regulating the
      morphology and dysmorphology of dendritic spines that underlie synaptic
      plasticity and neurological disorders, respectively. We summarize the influence
      of MMP-9 on the dynamic remodeling of the ECM via the cleavage of extracellular
      substrates. We discuss its role in the formation, modification, and maintenance
      of dendritic spines in learning and memory. Finally, we review research that
      implicates MMP-9 in aberrant synaptic plasticity and spine dysmorphology in
      neurological disorders, with a focus on morphological abnormalities of dendritic
      protrusions that are associated with epilepsy. 

PMID- 25071475
TI  - Claustrum projections to prefrontal cortex in the capuchin monkey (Cebus apella).
AB  - We examined the pattern of retrograde tracer distribution in the claustrum
      following intracortical injections into the frontal pole (area 10), and in dorsal
      (area 9), and ventral lateral (area 12) regions of the rostral prefrontal cortex
      in the tufted capuchin monkey (Cebus apella). The resulting pattern of labeled
      cells was assessed in relation to the three-dimensional geometry of the
      claustrum, as well as recent reports of claustrum-prefrontal connections in other
      primates. Claustrum-prefrontal projections were extensive, and largely
      concentrated in the ventral half of the claustrum, especially in the rostral 2/3
      of the nucleus. Our data are consistent with a topographic arrangement of
      claustrum-cortical connections in which prefrontal and association cortices
      receive connections largely from the rostral and medial claustrum. Comparative
      aspects of claustrum-prefrontal topography across primate species and the
      implications of claustrum connectivity for understanding of cortical functional
      networks are explored, and we hypothesize that the claustrum may play a role in
      controlling or switching between resting state and task-associated cortical
      networks. 

PMID- 25071476
TI  - Approach, avoidance, and their conflict: the problem of anchoring.

PMID- 25071477
TI  - Frequency-specific corticofugal modulation of the dorsal cochlear nucleus in
      mice.
AB  - The primary auditory cortex (AI) modulates the sound information processing in
      the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus
      (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a
      non-lemniscal subcortical nucleus but it is tonotopically organized like the
      AVCN. However, it remains unclear how the AI modulates the sound information
      processing in the DCN. This study examined the impact of focal electrical
      stimulation of AI on the auditory responses of the DCN neurons in mice. We found
      that the electrical stimulation induced significant changes in the best frequency
      (BF) of DCN neurons. The changes in the BFs were highly specific to the BF
      differences between the stimulated AI neurons and the recorded DCN neurons. The
      DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN
      BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed
      no change when the AI and DCN BFs were similar. Moreover, the BF shifts were
      linearly correlated to the BF differences. Thus, our data suggest that
      corticofugal modulation of the DCN is also highly specific to frequency
      information, similar to the corticofugal modulation of the AVCN. The frequency
      specificity of corticofugal modulation does not appear limited to the lemniscal
      ascending pathway. 

PMID- 25071479
TI  - Neuroenhancement by noninvasive brain stimulation is not a net zero-sum
      proposition.

PMID- 25071478
TI  - Neuroimaging, cognition, light and circadian rhythms.
AB  - In humans, sleep and wakefulness and the associated cognitive processes are
      regulated through interactions between sleep homeostasis and the circadian
      system. Chronic disruption of sleep and circadian rhythmicity is common in our
      society and there is a need for a better understanding of the brain mechanisms
      regulating sleep, wakefulness and associated cognitive processes. This review
      summarizes recent investigations which provide first neural correlates of the
      combined influence of sleep homeostasis and circadian rhythmicity on cognitive
      brain activity. Markers of interindividual variations in sleep-wake regulation,
      such as chronotype and polymorphisms in sleep and clock genes, are associated
      with changes in cognitive brain responses in subcortical and cortical areas in
      response to manipulations of the sleep-wake cycle. This review also includes
      recent data showing that cognitive brain activity is regulated by light, which is
      a powerful modulator of cognition and alertness and also directly impacts sleep
      and circadian rhythmicity. The effect of light varied with age, psychiatric
      status, PERIOD3 genotype and changes in sleep homeostasis and circadian phase.
      These data provide new insights into the contribution of demographic
      characteristics, the sleep-wake cycle, circadian rhythmicity and light to brain
      functioning. 

PMID- 25071480
TI  - Fixational eye movements and binocular vision.
AB  - During attempted visual fixation, small involuntary eye movements-called
      fixational eye movements-continuously change of our gaze's position. Disagreement
      between the left and right eye positions during such motions can produce diplopia
      (double vision). Thus, the ability to properly coordinate the two eyes during
      gaze fixation is critical for stable perception. For the last 50 years,
      researchers have studied the binocular characteristics of fixational eye
      movements. Here we review classical and recent studies on the binocular
      coordination (i.e., degree of conjugacy) of each fixational eye movement type:
      microsaccades, drift and tremor, and its perceptual contribution to increasing or
      reducing binocular disparity. We also discuss how amblyopia and other visual
      pathologies affect the binocular coordination of fixational eye movements. 

PMID- 25071482
TI  - Saccade-related activity in the prefrontal cortex: its role in eye movement
      control and cognitive functions.
AB  - Prefrontal neurons exhibit saccade-related activity and pre-saccadic memory
      related activity often encodes the directions of forthcoming eye movements, in
      line with demonstrated prefrontal contribution to flexible control of voluntary
      eye movements. However, many prefrontal neurons exhibit post-saccadic activity
      that is initiated well after the initiation of eye movement. Although post
      saccadic activity has been observed in the frontal eye field, this activity is
      thought to be a corollary discharge from oculomotor centers, because this
      activity shows no directional tuning and is observed whenever the monkeys perform
      eye movements regardless of goal-directed or not. However, prefrontal post
      saccadic activities exhibit directional tunings similar as pre-saccadic
      activities and show context dependency, such that post-saccadic activity is
      observed only when monkeys perform goal-directed saccades. Context-dependency of
      prefrontal post-saccadic activity suggests that this activity is not a result of
      corollary signals from oculomotor centers, but contributes to other functions of
      the prefrontal cortex. One function might be the termination of memory-related
      activity after a behavioral response is done. This is supported by the
      observation that the termination of memory-related activity coincides with the
      initiation of post-saccadic activity in population analyses of prefrontal
      activities. The termination of memory-related activity at the end of the trial
      ensures that the subjects can prepare to receive new and updated information.
      Another function might be the monitoring of behavioral performance, since the
      termination of memory-related activity by post-saccadic activity could be
      associated with informing the correctness of the response and the termination of
      the trial. However, further studies are needed to examine the characteristics of
      saccade-related activities in the prefrontal cortex and their functions in eye
      movement control and a variety of cognitive functions. 

PMID- 25071481
TI  - Vestibular function in the temporal and parietal cortex: distinct velocity and
      inertial processing pathways.
AB  - A number of behavioral and neuroimaging studies have reported converging data in
      favor of a cortical network for vestibular function, distributed between the
      temporo-parietal cortex and the prefrontal cortex in the primate. In this review,
      we focus on the role of the cerebral cortex in visuo-vestibular integration
      including the motion sensitive temporo-occipital areas i.e., the middle superior
      temporal area (MST) and the parietal cortex. Indeed, these two neighboring
      cortical regions, though they both receive combined vestibular and visual
      information, have distinct implications in vestibular function. In sum, this
      review of the literature leads to the idea of two separate cortical vestibular
      sub-systems forming (1) a velocity pathway including MST and direct descending
      pathways on vestibular nuclei. As it receives well-defined visual and vestibular
      velocity signals, this pathway is likely involved in heading perception and rapid
      top-down regulation of eye/head coordination and (2) an inertial processing
      pathway involving the parietal cortex in connection with the subcortical
      vestibular nuclei complex responsible for velocity storage integration. This
      vestibular cortical pathway would be implicated in high-order multimodal
      integration and cognitive functions, including world space and self-referential
      processing. 

PMID- 25071483
TI  - Shaping the learning curve: epigenetic dynamics in neural plasticity.
AB  - A key characteristic of learning and neural plasticity is state-dependent
      acquisition dynamics reflected by the non-linear learning curve that links
      increase in learning with practice. Here we propose that the manner by which
      epigenetic states of individual cells change during learning contributes to the
      shape of the neural and behavioral learning curve. We base our suggestion on
      recent studies showing that epigenetic mechanisms such as DNA methylation,
      histone acetylation, and RNA-mediated gene regulation are intimately involved in
      the establishment and maintenance of long-term neural plasticity, reflecting
      specific learning-histories and influencing future learning. Our model, which is
      the first to suggest a dynamic molecular account of the shape of the learning
      curve, leads to several testable predictions regarding the link between
      epigenetic dynamics at the promoter, gene-network, and neural-network levels.
      This perspective opens up new avenues for therapeutic interventions in
      neurological pathologies. 

PMID- 25071484
TI  - Functional correlates of optic flow motion processing in Parkinson's disease.
AB  - The visual input created by the relative motion between an individual and the
      environment, also called optic flow, influences the sense of self-motion,
      postural orientation, veering of gait, and visuospatial cognition. An optic flow
      network comprising visual motion areas V6, V3A, and MT+, as well as visuo
      vestibular areas including posterior insula vestibular cortex (PIVC) and
      cingulate sulcus visual area (CSv), has been described as uniquely selective for
      parsing egomotion depth cues in humans. Individuals with Parkinson's disease (PD)
      have known behavioral deficits in optic flow perception and visuospatial
      cognition compared to age- and education-matched control adults (MC). The present
      study used functional magnetic resonance imaging (fMRI) to investigate neural
      correlates related to impaired optic flow perception in PD. We conducted fMRI on
      40 non-demented participants (23 PD and 17 MC) during passive viewing of
      simulated optic flow motion and random motion. We hypothesized that compared to
      the MC group, PD participants would show abnormal neural activity in regions
      comprising this optic flow network. MC participants showed robust activation
      across all regions in the optic flow network, consistent with studies in young
      adults, suggesting intact optic flow perception at the neural level in healthy
      aging. PD participants showed diminished activity compared to MC particularly
      within visual motion area MT+ and the visuo-vestibular region CSv. Further,
      activation in visuo-vestibular region CSv was associated with disease severity.
      These findings suggest that behavioral reports of impaired optic flow perception
      and visuospatial performance may be a result of impaired neural processing within
      visual motion and visuo-vestibular regions in PD. 

PMID- 25071486
TI  - Olfactory preference conditioning changes the reward value of reinforced and non
      reinforced odors.
AB  - Olfaction is determinant for the organization of rodent behavior. In a feeding
      context, rodents must quickly discriminate whether a nutrient can be ingested or
      whether it represents a potential danger to them. To understand the learning
      processes that support food choice, aversive olfactory learning and flavor
      appetitive learning have been extensively studied. In contrast, little is
      currently known about olfactory appetitive learning and its mechanisms. We
      designed a new paradigm to study conditioned olfactory preference in rats. After
      8 days of exposure to a pair of odors (one paired with sucrose and the other with
      water), rats developed a strong and stable preference for the odor associated
      with the sucrose solution. A series of experiments were conducted to further
      analyze changes in reward value induced by this paradigm for both stimuli. As
      expected, the reward value of the reinforced odor changed positively.
      Interestingly, the reward value of the alternative odor decreased. This
      devaluation had an impact on further odor comparisons that the animal had to
      make. This result suggests that appetitive conditioning involving a comparison
      between two odors not only leads to a change in the reward value of the
      reinforced odor, but also induces a stable devaluation of the non-reinforced
      stimulus. 

PMID- 25071487
TI  - Neuronal and psychological underpinnings of pathological gambling.

PMID- 25071485
TI  - The development and malleability of executive control abilities.
AB  - Executive control (EC) generally refers to the regulation of mental activity. It
      plays a crucial role in complex cognition, and EC skills predict high-level
      abilities including language processing, memory, and problem solving, as well as
      practically relevant outcomes such as scholastic achievement. EC develops
      relatively late in ontogeny, and many sub-groups of developmental populations
      demonstrate an exaggeratedly poor ability to control cognition even alongside the
      normal protracted growth of EC skills. Given the value of EC to human
      performance, researchers have sought means to improve it through targeted
      training; indeed, accumulating evidence suggests that regulatory processes are
      malleable through experience and practice. Nonetheless, there is a need to
      understand both whether specific populations might particularly benefit from
      training, and what cortical mechanisms engage during performance of the tasks
      used in the training protocols. This contribution has two parts: in Part I, we
      review EC development and intervention work in select populations. Although
      promising, the mixed results in this early field make it difficult to draw strong
      conclusions. To guide future studies, in Part II, we discuss training studies
      that have included a neuroimaging component - a relatively new enterprise that
      also has not yet yielded a consistent pattern of results post-training,
      preventing broad conclusions. We therefore suggest that recent developments in
      neuroimaging (e.g., multivariate and connectivity approaches) may be useful to
      advance our understanding of the neural mechanisms underlying the malleability of
      EC and brain plasticity. In conjunction with behavioral data, these methods may
      further inform our understanding of the brain-behavior relationship and the
      extent to which EC is dynamic and malleable, guiding the development of future,
      targeted interventions to promote executive functioning in both healthy and
      atypical populations. 

PMID- 25071488
TI  - Impairment in extinction of contextual and cued fear following post-training
      whole-body irradiation.
AB  - Because of the use of radiation in cancer therapy, the risk of nuclear
      contamination from power plants, military conflicts, and terrorism, there is a
      compelling scientific and public health interest in the effects of environmental
      radiation exposure on brain function, in particular hippocampal function and
      learning and memory. Previous studies have emphasized changes in learning and
      memory following radiation exposure. These approaches have ignored the question
      of how radiation exposure might impact recently acquired memories, which might be
      acquired under traumatic circumstances (cancer treatment, nuclear disaster,
      etc.). To address the question of how radiation exposure might affect the
      processing and recall of recently acquired memories, we employed a fear
      conditioning paradigm wherein animals were trained, and subsequently irradiated
      (whole-body X-ray irradiation) 24 h later. Animals were given 2 weeks to recover,
      and were tested for retention and extinction of hippocampus-dependent contextual
      fear conditioning or hippocampus-independent cued fear conditioning. Exposure to
      irradiation following training was associated with reduced daily increases in
      body weights over the 22-days of the study and resulted in greater freezing
      levels and aberrant extinction 2 weeks later. This was also observed when the
      intensity of the training protocol was increased. Cued freezing levels and
      measures of anxiety 2 weeks after training were also higher in irradiated than
      sham-irradiated mice. In contrast to contextual freezing levels, cued freezing
      levels were even higher in irradiated mice receiving 5 shocks during training
      than sham-irradiated mice receiving 10 shocks during training. In addition, the
      effects of radiation on extinction of contextual fear were more profound than
      those on the extinction of cued fear. Thus, whole-body irradiation elevates
      contextual and cued fear memory recall. 

PMID- 25071489
TI  - Conscious recall of different aspects of skill memory.
AB  - Different mechanisms are involved in the formation of memories necessary for
      daily living. For example, different memory representations are formed for the
      practiced transitions between key-presses (i.e., pressing key "2" after "3" in "4
      3-2-1") and for the ordinal position of each key-press (i.e., pressing key "2" in
      the third ordinal position in "4-3-2-1") in a motor sequence. Whether the
      resulting transition-based and ordinal-based memories (Song and Cohen, 2014) can
      be consciously recalled is unknown. Here, we studied subjects who over a week of
      training and testing formed transition and ordinal-based memory representations
      of skill for a 12-item sequence of key-presses. Afterwards, subjects were first
      asked to recall and type the trained sequence and then to perform random key
      presses avoiding the trained sequence. The difference in the ability to
      purposefully recall and avoid a trained sequence represents conscious recall
      (Destrebecqz and Cleeremans, 2001). We report that (a) the difference in the
      ability to purposefully recall and to avoid the trained sequence correlated with
      ordinal-based but not with transition-based memory; (b) subjects with no ability
      to recall or avoid the trained sequence formed transition-based but not ordinal
      based memories; and (c) subjects with full ability to recall and avoid the
      trained sequence formed both transition-based and ordinal-based memories. We
      conclude that ordinal-based memory can be voluntarily recalled when transition
      based memory cannot, documenting a differential capacity to recall memories
      forming a motor skill. Understanding that different memories form a motor skill,
      with different neural substrates (Cohen and Squire, 1980), may help develop novel
      training strategies in neurorehabilitation of patients with brain lesions. 

PMID- 25071490
TI  - Prefronto-striatal physiology is associated with schizotypy and is modulated by a
      functional variant of DRD2.
AB  - "Schizotypy" is a latent organization of personality related to the genetic risk
      for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share
      some biological features, including a link to dopaminergic D2 receptor signaling.
      A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has
      been associated with the D2 short/long isoform expression ratio, as well as
      striatal dopamine signaling and prefrontal cortical activity during different
      cognitive operations, which are measures that are altered in patients with
      schizophrenia. Our aim is to determine the association of schizotypy scores with
      the DRD2 rs1076560 genotype in healthy individuals and their interaction with
      prefrontal activity during attention and D2 striatal signaling. A total of 83
      healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal
      Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with
      [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control
      task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than
      GG individuals. Moreover, the interaction between schizotypy and the GT genotype
      predicted prefrontal activity and related attentional behavior, as well as
      striatal binding of IBZM. No interaction was found in GG individuals. These
      results suggest that rs1076560 GT healthy individuals are prone to higher levels
      of schizotypy, and that the interaction between rs1076560 and schizotypy scores
      modulates phenotypes related to the pathophysiology of schizophrenia, such as
      prefrontal activity and striatal dopamine signaling. These results provide
      systems-level qualitative evidence for mapping the construct of schizotypy in
      healthy individuals onto the schizophrenia continuum. 

PMID- 25071491
TI  - Individual differences in bodily freezing predict emotional biases in decision
      making.
AB  - Instrumental decision making has long been argued to be vulnerable to emotional
      responses. Literature on multiple decision making systems suggests that this
      emotional biasing might reflect effects of a system that regulates innately
      specified, evolutionarily preprogrammed responses. To test this hypothesis
      directly, we investigated whether effects of emotional faces on instrumental
      action can be predicted by effects of emotional faces on bodily freezing, an
      innately specified response to aversive relative to appetitive cues. We tested 43
      women using a novel emotional decision making task combined with posturography,
      which involves a force platform to detect small oscillations of the body to
      accurately quantify postural control in upright stance. On the platform,
      participants learned whole body approach-avoidance actions based on monetary
      feedback, while being primed by emotional faces (angry/happy). Our data evidence
      an emotional biasing of instrumental action. Thus, angry relative to happy faces
      slowed instrumental approach relative to avoidance responses. Critically,
      individual differences in this emotional biasing effect were predicted by
      individual differences in bodily freezing. This result suggests that emotional
      biasing of instrumental action involves interaction with a system that controls
      innately specified responses. Furthermore, our findings help bridge (animal and
      human) decision making and emotion research to advance our mechanistic
      understanding of decision making anomalies in daily encounters as well as in a
      wide range of psychopathology. 

PMID- 25071493
TI  - Corrigendum: CREB activity in dopamine D1 receptor expressing neurons regulates
      cocaine-induced behavioral effects.

PMID- 25071492
TI  - Properties and mechanisms of olfactory learning and memory.
AB  - Memories are dynamic physical phenomena with psychometric forms as well as
      characteristic timescales. Most of our understanding of the cellular mechanisms
      underlying the neurophysiology of memory, however, derives from one-trial
      learning paradigms that, while powerful, do not fully embody the gradual,
      representational, and statistical aspects of cumulative learning. The early
      olfactory system-particularly olfactory bulb-comprises a reasonably well
      understood and experimentally accessible neuronal network with intrinsic
      plasticity that underlies both one-trial (adult aversive, neonatal) and
      cumulative (adult appetitive) odor learning. These olfactory circuits employ many
      of the same molecular and structural mechanisms of memory as, for example,
      hippocampal circuits following inhibitory avoidance conditioning, but the
      temporal sequences of post-conditioning molecular events are likely to differ
      owing to the need to incorporate new information from ongoing learning events
      into the evolving memory trace. Moreover, the shapes of acquired odor
      representations, and their gradual transformation over the course of cumulative
      learning, also can be directly measured, adding an additional representational
      dimension to the traditional metrics of memory strength and persistence. In this
      review, we describe some established molecular and structural mechanisms of
      memory with a focus on the timecourses of post-conditioning molecular processes.
      We describe the properties of odor learning intrinsic to the olfactory bulb and
      review the utility of the olfactory system of adult rodents as a memory system in
      which to study the cellular mechanisms of cumulative learning. 

PMID- 25071496
TI  - The principal sources of William James' idea of habit.

PMID- 25071494
TI  - A review on the neural bases of episodic odor memory: from laboratory-based to
      autobiographical approaches.
AB  - Odors are powerful cues that trigger episodic memories. However, in light of the
      amount of behavioral data describing the characteristics of episodic odor memory,
      the paucity of information available on the neural substrates of this function is
      startling. Furthermore, the diversity of experimental paradigms complicates the
      identification of a generic episodic odor memory network. We conduct a systematic
      review of the literature depicting the current state of the neural correlates of
      episodic odor memory in healthy humans by placing a focus on the experimental
      approaches. Functional neuroimaging data are introduced by a brief
      characterization of the memory processes investigated. We present and discuss
      laboratory-based approaches, such as odor recognition and odor associative
      memory, and autobiographical approaches, such as the evaluation of odor
      familiarity and odor-evoked autobiographical memory. We then suggest the
      development of new laboratory-ecological approaches allowing for the controlled
      encoding and retrieval of specific multidimensional events that could open up new
      prospects for the comprehension of episodic odor memory and its neural
      underpinnings. While large conceptual differences distinguish experimental
      approaches, the overview of the functional neuroimaging findings suggests
      relatively stable neural correlates of episodic odor memory. 

PMID- 25071495
TI  - The relationship between different facets of empathy, pain perception and
      compassion fatigue among physicians.
AB  - BACKGROUND: Medical practitioners such as physicians are continuously exposed to
      the suffering and the distress of patients. Understanding the way pain perception
      relates to empathetic dispositions and professional quality of life can
      contribute to the development of strategies aimed at protecting health
      professionals from burnout and compassion fatigue. In the present study we
      investigate the way individual dispositions relate to behavioral measures of pain
      sensitivity, empathy, and professional quality of life. METHODS: A secure Web
      based series of self-report measures and a behavioral task were administered to
      1,199 board-certified physicians. Additionally, surveys were used to obtain
      measures of demographic and professional background; dispositional empathy
      (empathic concern, personal distress, and perspective taking); positive
      (compassion satisfaction) and negative (burnout and secondary traumatic stress)
      aspects of their professional life. In the behavioral task, participants were
      asked to watch a series of video clips of patients experiencing different levels
      of pain and provide ratings of pain intensity and induced personal distress.
      RESULTS: Perceived pain intensity was significantly lower among more experienced
      physicians but similar across specialty fields with varying demands of emotional
      stress. Watching videos of patients in pain, however, elicited more personal
      distress among physicians in highly demanding medical fields, despite comparable
      empathy dispositions with other fields. The pain of male patients was perceived
      as less intense than the pain of female patients, and this effect was more marked
      for female physicians. The effect of dispositional empathy on pain perception and
      induced personal distress was different for each sub-component, with perspective
      taking and empathic concern (EC) being predictive of the behavioral outcomes.
      Physicians who experience both compassion satisfaction and fatigue perceive more
      pain and suffer more personal distress from it than those who only suffer the
      negative aspects of professional quality of life. CONCLUSIONS: Professional
      experience seems to desensitize physicians to the pain of others without
      necessarily helping them down-regulate their own personal distress. Pain
      perception is also related with specific aspects of empathy and varies depending
      on context, as is the case with the gender of their patients. Minimum levels of
      empathy appear necessary to benefit from the positive aspects of professional
      quality of life in medicine.

PMID- 25071497
TI  - A model-based analysis of impulsivity using a slot-machine gambling paradigm.
AB  - Impulsivity plays a key role in decision-making under uncertainty. It is a
      significant contributor to problem and pathological gambling (PG). Standard
      assessments of impulsivity by questionnaires, however, have various limitations,
      partly because impulsivity is a broad, multi-faceted concept. What remains
      unclear is which of these facets contribute to shaping gambling behavior. In the
      present study, we investigated impulsivity as expressed in a gambling setting by
      applying computational modeling to data from 47 healthy male volunteers who
      played a realistic, virtual slot-machine gambling task. Behaviorally, we found
      that impulsivity, as measured independently by the 11th revision of the Barratt
      Impulsiveness Scale (BIS-11), correlated significantly with an aggregate read-out
      of the following gambling responses: bet increases (BIs), machines switches (MS),
      casino switches (CS), and double-ups (DUs). Using model comparison, we compared a
      set of hierarchical Bayesian belief-updating models, i.e., the Hierarchical
      Gaussian Filter (HGF) and Rescorla-Wagner reinforcement learning (RL) models,
      with regard to how well they explained different aspects of the behavioral data.
      We then examined the construct validity of our winning models with multiple
      regression, relating subject-specific model parameter estimates to the individual
      BIS-11 total scores. In the most predictive model (a three-level HGF), the two
      free parameters encoded uncertainty-dependent mechanisms of belief updates and
      significantly explained BIS-11 variance across subjects. Furthermore, in this
      model, decision noise was a function of trial-wise uncertainty about winning
      probability. Collectively, our results provide a proof of concept that
      hierarchical Bayesian models can characterize the decision-making mechanisms
      linked to the impulsive traits of an individual. These novel indices of gambling
      mechanisms unmasked during actual play may be useful for online prevention
      measures for at-risk players and future assessments of PG. 

PMID- 25071498
TI  - An extended case study on the phenomenology of sequence-space synesthesia.
AB  - Investigation of synesthesia phenomenology in adults is needed to constrain
      accounts of developmental trajectories of this trait. We report an extended
      phenomenological investigation of sequence-space synesthesia in a single case
      (AB). We used the Elicitation Interview (EI) method to facilitate repeated
      exploration of AB's synesthetic experience. During an EI the subject's attention
      is selectively guided by the interviewer in order to reveal precise details about
      the experience. Detailed analysis of the resulting 9 h of interview transcripts
      provided a comprehensive description of AB's synesthetic experience, including
      several novel observations. For example, we describe a specific spatial reference
      frame (a "mental room") in which AB's concurrents occur, and which overlays his
      perception of the real world (the "physical room"). AB is able to switch his
      attention voluntarily between this mental room and the physical room.
      Exemplifying the EI method, some of our observations were previously unknown even
      to AB. For example, AB initially reported to experience concurrents following
      visual presentation, yet we determined that in the majority of cases the
      concurrent followed an internal verbalization of the inducer, indicating an
      auditory component to sequence-space synesthesia. This finding is congruent with
      typical rehearsal of inducer sequences during development, implicating cross
      modal interactions between auditory and visual systems in the genesis of this
      synesthetic form. To our knowledge, this paper describes the first application of
      an EI to synesthesia, and the first systematic longitudinal investigation of the
      first-person experience of synesthesia since the re-emergence of interest in this
      topic in the 1980's. These descriptions move beyond rudimentary graphical or
      spatial representations of the synesthetic spatial form, thereby providing new
      targets for neurobehavioral analysis. 

PMID- 25071500
TI  - Insights from introspection: a commentary on Gould et al. (2014), "An extended
      case study on the phenomenology of spatial form synaesthesia".

PMID- 25071499
TI  - What kind of science for psychiatry?
AB  - Psychiatry has invested its hopes in neuroscience as a path to understanding
      mental disorders and developing more effective treatments and ultimately cures.
      Recently, the U.S. NIMH has elaborated this vision through a new framework for
      mental health research, the Research Domain Criteria (RDoC). This framework aims
      to orient mental health research toward the discovery of underlying
      neurobiological and biobehavioral mechanisms of mental disorders that will
      eventually lead to definitive treatments. In this article we consider the
      rationale of the RDoC and what it reveals about implicit models of mental
      disorders. As an overall framework for understanding mental disorders, RDoC is
      impoverished and conceptually flawed. These limitations are not accidental but
      stem from disciplinary commitments and interests that are at odds with the larger
      concerns of psychiatry. A multilevel, ecosocial approach to biobehavioral systems
      is needed both to guide relevant neuroscience research and insure the inclusion
      of social processes that may be fundamental contributors to psychopathology and
      recovery. 

PMID- 25071501
TI  - Noisy visual feedback training impairs detection of self-generated movement
      error: implications for anosognosia for hemiplegia.
AB  - Anosognosia for hemiplegia (AHP) is characterized as a disorder in which patients
      are unaware of their contralateral motor deficit. Many current theories for
      unawareness in AHP are based on comparator model accounts of the normal
      experience of agency. According to such models, while small mismatches between
      predicted and actual feedback allow unconscious fine-tuning of normal actions,
      mismatches that surpass an inherent threshold reach conscious awareness and
      inform judgments of agency (whether a given movement is produced by the self or
      another agent). This theory depends on a threshold for consciousness that is
      greater than the intrinsic noise in the system to reduce the occurrence of
      incorrect rejections of self-generated movements and maintain a fluid experience
      of agency. Pathological increases to this threshold could account for reduced
      motor awareness following brain injury, including AHP. The current experiment
      tested this hypothesis in healthy controls by exposing them to training in which
      noise was applied the visual feedback of their normal reaches. Subsequent
      self/other attribution tasks without noise revealed a decrease in the ability to
      detect manipulated (other) feedback compared to training without noise. This
      suggests a slackening of awareness thresholds in the comparator model that may
      help to explain clinical observations of decreased action awareness following
      stroke. 

PMID- 25071504
TI  - Tracking orthographic learning in children with different profiles of reading
      difficulty.
AB  - Previous studies have found that children with reading difficulties need more
      exposures to acquire the representations needed to support fluent reading than
      typically developing readers (e.g., Ehri and Saltmarsh, 1995). Building on
      existing orthographic learning paradigms, we report on an investigation of
      orthographic learning in poor readers using a new learning task tracking both the
      accuracy (untimed exposure duration) and fluency (200 ms exposure duration) of
      learning novel words over trials. In study 1, we used the paradigm to examine
      orthographic learning in children with specific poor reader profiles (nine with a
      surface profile, nine a phonological profile) and nine age-matched controls. Both
      profiles showed improvement over the learning cycles, but the children with
      surface profile showed impaired orthographic learning in spelling and
      orthographic choice tasks. Study 2 explored predictors of orthographic learning
      in a group of 91 poor readers using the same outcome measures as in Study 1.
      Consistent with earlier findings in typically developing readers, phonological
      decoding skill predicted orthographic learning. Moreover, orthographic knowledge
      significantly predicted orthographic learning over and beyond phonological
      decoding. The two studies provide insights into how poor readers learn novel
      words, and how their learning process may be compromised by less proficient
      orthographic and/or phonological skills. 

PMID- 25071503
TI  - Deficient approaches to human neuroimaging.
AB  - Functional magnetic resonance imaging (fMRI) is the workhorse of imaging-based
      human cognitive neuroscience. The use of fMRI is ever-increasing; within the last
      4 years more fMRI studies have been published than in the previous 17 years. This
      large body of research has mainly focused on the functional localization of
      condition- or stimulus-dependent changes in the blood-oxygenation-level dependent
      signal. In recent years, however, many aspects of the commonly practiced analysis
      frameworks and methodologies have been critically reassessed. Here we summarize
      these critiques, providing an overview of the major conceptual and practical
      deficiencies in widely used brain-mapping approaches, and exemplify some of these
      issues by the use of imaging data and simulations. In particular, we discuss the
      inherent pitfalls and shortcomings of methodologies for statistical parametric
      mapping. Our critique emphasizes recent reports of excessively high numbers of
      both false positive and false negative findings in fMRI brain mapping. We outline
      our view regarding the broader scientific implications of these methodological
      considerations and briefly discuss possible solutions. 

PMID- 25071502
TI  - Precision grip in congenital and acquired hemiparesis: similarities in
      impairments and implications for neurorehabilitation.
AB  - BACKGROUND: Patients with congenital and acquired hemiparesis incur long-term
      functional deficits, among which the loss of prehension that may impact their
      functional independence. Identifying, understanding, and comparing the underlying
      mechanisms of prehension impairments represent an opportunity to better adapt
      neurorehabilitation. OBJECTIVE: The present review aims to provide a better
      understanding of precision grip deficits in congenital and acquired hemiparesis
      and to determine whether the severity and type of fine motor control impairments
      depend on whether or not the lesions are congenital or acquired in adulthood.
      METHODS: Using combinations of the following key words: fingertip force, grip
      force, precision grip, cerebral palsy, stroke, PubMed, and Scopus databases were
      used to search studies from 1984 to 2013. RESULTS: Individuals with both
      congenital and acquired hemiparesis were able to some extent to use anticipatory
      motor control in precision grip tasks, even if this control was impaired in the
      paretic hand. In both congenital and acquired hemiparesis, the ability to plan
      efficient anticipatory motor control when the less-affected hand is used provides
      a possibility to remediate impairments in anticipatory motor control of the
      paretic hand. CONCLUSION: Surprisingly, we observed very few differences between
      the results of studies in children with congenital hemiplegia and stroke
      patients. We suggest that the underlying specific strategies of
      neurorehabilitation developed for each one could benefit the other.

PMID- 25071505
TI  - Short time sports exercise boosts motor imagery patterns: implications of mental
      practice in rehabilitation programs.
AB  - Motor imagery (MI) is a commonly used paradigm for the study of motor learning or
      cognitive aspects of action control. The rationale for using MI training to
      promote the relearning of motor function arises from research on the functional
      correlates that MI shares with the execution of physical movements. While most of
      the previous studies investigating MI were based on simple movements in the
      present study a more attractive mental practice was used to investigate cortical
      activation during MI. We measured cerebral responses with functional magnetic
      resonance imaging (fMRI) in twenty three healthy volunteers as they imagined
      playing soccer or tennis before and after a short physical sports exercise. Our
      results demonstrated that only 10 min of training are enough to boost MI patterns
      in motor related brain regions including premotor cortex and supplementary motor
      area (SMA) but also fronto-parietal and subcortical structures. This supports
      previous findings that MI has beneficial effects especially in combination with
      motor execution when used in motor rehabilitation or motor learning processes. We
      conclude that sports MI combined with an interactive game environment could be a
      promising additional tool in future rehabilitation programs aiming to improve
      upper or lower limb functions or support neuroplasticity. 

PMID- 25071506
TI  - The marketing firm and consumer choice: implications of bilateral contingency for
      levels of analysis in organizational neuroscience.
AB  - The emergence of a conception of the marketing firm (Foxall, 1999a) conceived
      within behavioral psychology and based on a corresponding model of consumer
      choice, (Foxall, 1990/2004) permits an assessment of the levels of behavioral and
      organizational analysis amenable to neuroscientific examination. This paper
      explores the ways in which the bilateral contingencies that link the marketing
      firm with its consumerate allow appropriate levels of organizational
      neuroscientific analysis to be specified. Having described the concept of the
      marketing firm and the model of consumer behavior on which it is based, the paper
      analyzes bilateral contingencies at the levels of (i) market exchange, (ii)
      emotional reward, and (iii) neuroeconomics. Market exchange emerges as a level of
      analysis that lends itself predominantly to the explanation of firm-consumerate
      interactions in terms of the super-personal level of reinforcing and punishing
      contingencies: the marketing firm can be treated as a contextual or operant
      system in its own right. However, the emotional reward and neuroeconomic levels
      of analysis should be confined to the personal level of analysis represented by
      individual managers on the one hand and individual consumers on the other. This
      also entails a level of abstraction but it is one that can be satisfactorily
      handled in terms of the concept of bilateral contingency. 

PMID- 25071507
TI  - Brain-potential analysis of visual word recognition in dyslexics and typically
      reading children.
AB  - The specialization of visual brain areas for fast processing of printed words
      plays an important role in the acquisition of reading skills. Dysregulation of
      these areas may be among the deficits underlying developmental dyslexia. The
      present study examines the specificity of word activation in dyslexic children in
      3rd grade by comparing early components of brain potentials elicited by visually
      presented words vs. strings of meaningless letter-like symbols. Results showed a
      more pronounced N1 component for words compared to symbols for both groups. The
      dyslexic group revealed larger left-lateralized, word-specific N1 responses than
      the typically reading group. Furthermore, positive correlations between N1
      amplitudes and reading fluency were found in the dyslexic group. Our results
      support the notion of N1 as a sensitive index of visual word processing involved
      in reading fluency. 

PMID- 25071508
TI  - Difference in brain activations during appreciating paintings and photographic
      analogs.
AB  - Several studies have investigated neural correlates of aesthetic appreciation for
      paintings but to date the findings have been heterogeneous. This heterogeneity
      may be attributed to previous studies' measurement of aesthetic appreciation of
      not only the beauty of paintings but also the beauty of motifs of the paintings.
      In order to better elucidate the beauty of paintings, it seems necessary to
      compare aesthetic appreciation of paintings and photographic analogs which
      included corresponding real images. We prepared for famous painters' pictures and
      their photographic analogs which were set up to resemble each painting in order
      to investigate the hypothesis that there exist specific neural correlates
      associated with the aesthetic appreciation for paintings. Forty-four subjects
      participated in functional magnetic resonance study which required comparisons of
      aesthetic appreciation of paintings of still life and landscape versus
      photographic analogs including corresponding real images of still life and
      landscape. Bilateral cuneus and the left lingual gyrus were activated in the
      comparison of aesthetic appreciation of paintings versus photographic analogs. In
      conclusion, the present findings suggest a possibility of the existence of
      specific neural correlates associated with the aesthetic appreciation for
      paintings and that bilateral cuneus and the left lingual gyrus may be involved. 

PMID- 25071509
TI  - Visual processing of multiple elements in the dyslexic brain: evidence for a
      superior parietal dysfunction.
AB  - The visual attention (VA) span deficit hypothesis of developmental dyslexia
      posits that impaired multiple element processing can be responsible for poor
      reading outcomes. In VA span impaired dyslexic children, poor performance on
      letter report tasks is associated with reduced parietal activations for multiple
      letter processing. While this hints towards a non-specific, attention-based
      dysfunction, it is still unclear whether reduced parietal activity generalizes to
      other types of stimuli. Furthermore, putative links between reduced parietal
      activity and reduced ventral occipito-temporal (vOT) in dyslexia have yet to be
      explored. Using functional magnetic resonance imaging, we measured brain activity
      in 12 VA span impaired dyslexic adults and 12 adult skilled readers while they
      carried out a categorization task on single or multiple alphanumeric or non
      alphanumeric characters. While healthy readers activated parietal areas more
      strongly for multiple than single element processing (right-sided for
      alphanumeric and bilateral for non-alphanumeric), similar stronger multiple
      element right parietal activations were absent for dyslexic participants.
      Contrasts between skilled and dyslexic readers revealed significantly reduced
      right superior parietal lobule (SPL) activity for dyslexic readers regardless of
      stimuli type. Using a priori anatomically defined regions of interest, we showed
      that neural activity was reduced for dyslexic participants in both SPL and vOT
      bilaterally. Finally, we used multiple regressions to test whether SPL activity
      was related to vOT activity in each group. In the left hemisphere, SPL activity
      covaried with vOT activity for both normal and dyslexic readers. In contrast, in
      the right hemisphere, SPL activity covaried with vOT activity only for dyslexic
      readers. These results bring critical support to the VA interpretation of the VA
      Span deficit. In addition, they offer a new insight on how deficits in automatic
      vOT based word recognition could arise in developmental dyslexia. 

PMID- 25071510
TI  - Novel method to classify hemodynamic response obtained using multi-channel fNIRS
      measurements into two groups: exploring the combinations of channels.
AB  - Near-infrared spectroscopy (NIRS) in psychiatric studies has widely demonstrated
      that cerebral hemodynamics differs among psychiatric patients. Recently we found
      that children with attention-deficit/hyperactivity disorder (ADHD) and children
      with autism spectrum disorders (ASD) showed different hemodynamic responses to
      their own mother's face. Based on this finding, we may be able to classify the
      hemodynamic data into two those groups and predict to which diagnostic group an
      unknown participant belongs. In the present study, we proposed a novel
      statistical method for classifying the hemodynamic data of these two groups. By
      applying a support vector machine (SVM), we searched the combination of
      measurement channels at which the hemodynamic response differed between the ADHD
      and the ASD children. The SVM found the optimal subset of channels in each data
      set and successfully classified the ADHD data from the ASD data. For the 24
      dimensional hemodynamic data, two optimal subsets classified the hemodynamic data
      with 84% classification accuracy, while the subset contained all 24 channels
      classified with 62% classification accuracy. These results indicate the potential
      application of our novel method for classifying the hemodynamic data into two
      groups and revealing the combinations of channels that efficiently differentiate
      the two groups. 

PMID- 25071511
TI  - COMT Val(158)Met genotypes differentially influence subgenual cingulate
      functional connectivity in healthy females.
AB  - Brain imaging studies have consistently shown subgenual Anterior Cingulate
      Cortical (sgACC) involvement in emotion processing. catechol-O-methyltransferase
      (COMT) Val(158) and Met(158) polymorphisms may influence such emotional brain
      processes in specific ways. Given that resting-state fMRI (rsfMRI) may increase
      our understanding on brain functioning, we integrated genetic and rsfMRI data and
      focused on sgACC functional connections. No studies have yet investigated the
      influence of the COMT Val(158)Met polymorphism (rs4680) on sgACC resting-state
      functional connectivity (rsFC) in healthy individuals. A homogeneous group of 61
      Caucasian right-handed healthy female university students, all within the same
      age range, underwent rsfMRI. Compared to Met(158) homozygotes, Val(158) allele
      carriers displayed significantly stronger rsFC between the sgACC and the left
      parahippocampal gyrus, ventromedial parts of the inferior frontal gyrus (IFG),
      and the nucleus accumbens (NAc). On the other hand, compared to Val(158)
      homozygotes, we found in Met(158) allele carriers stronger sgACC rsFC with the
      medial frontal gyrus (MFG), more in particular the anterior parts of the medial
      orbitofrontal cortex. Although we did not use emotional or cognitive tasks, our
      sgACC rsFC results point to possible distinct differences in emotional and
      cognitive processes between Val(158) and Met(158) allele carriers. However, the
      exact nature of these directions remains to be determined. 

PMID- 25071512
TI  - The relationship of phonological ability, speech perception, and auditory
      perception in adults with dyslexia.
AB  - This study investigated whether auditory, speech perception, and phonological
      skills are tightly interrelated or independently contributing to reading. We
      assessed each of these three skills in 36 adults with a past diagnosis of
      dyslexia and 54 matched normal reading adults. Phonological skills were tested by
      the typical threefold tasks, i.e., rapid automatic naming, verbal short-term
      memory and phonological awareness. Dynamic auditory processing skills were
      assessed by means of a frequency modulation (FM) and an amplitude rise time (RT);
      an intensity discrimination task (ID) was included as a non-dynamic control task.
      Speech perception was assessed by means of sentences and words-in-noise tasks.
      Group analyses revealed significant group differences in auditory tasks (i.e., RT
      and ID) and in phonological processing measures, yet no differences were found
      for speech perception. In addition, performance on RT discrimination correlated
      with reading but this relation was mediated by phonological processing and not by
      speech-in-noise. Finally, inspection of the individual scores revealed that the
      dyslexic readers showed an increased proportion of deviant subjects on the slow
      dynamic auditory and phonological tasks, yet each individual dyslexic reader does
      not display a clear pattern of deficiencies across the processing skills.
      Although our results support phonological and slow-rate dynamic auditory deficits
      which relate to literacy, they suggest that at the individual level, problems in
      reading and writing cannot be explained by the cascading auditory theory.
      Instead, dyslexic adults seem to vary considerably in the extent to which each of
      the auditory and phonological factors are expressed and interact with
      environmental and higher-order cognitive influences. 

PMID- 25071513
TI  - Individual differences in cortical face selectivity predict behavioral
      performance in face recognition.
AB  - In functional magnetic resonance imaging studies, object selectivity is defined
      as a higher neural response to an object category than other object categories.
      Importantly, object selectivity is widely considered as a neural signature of a
      functionally-specialized area in processing its preferred object category in the
      human brain. However, the behavioral significance of the object selectivity
      remains unclear. In the present study, we used the individual differences
      approach to correlate participants' face selectivity in the face-selective
      regions with their behavioral performance in face recognition measured outside
      the scanner in a large sample of healthy adults. Face selectivity was defined as
      the z score of activation with the contrast of faces vs. non-face objects, and
      the face recognition ability was indexed as the normalized residual of the
      accuracy in recognizing previously-learned faces after regressing out that for
      non-face objects in an old/new memory task. We found that the participants with
      higher face selectivity in the fusiform face area (FFA) and the occipital face
      area (OFA), but not in the posterior part of the superior temporal sulcus (pSTS),
      possessed higher face recognition ability. Importantly, the association of face
      selectivity in the FFA and face recognition ability cannot be accounted for by
      FFA response to objects or behavioral performance in object recognition,
      suggesting that the association is domain-specific. Finally, the association is
      reliable, confirmed by the replication from another independent participant
      group. In sum, our finding provides empirical evidence on the validity of using
      object selectivity as a neural signature in defining object-selective regions in
      the human brain. 

PMID- 25071514
TI  - Walking strategies in subjects with congenital or early onset strabismus.
AB  - INTRODUCTION: In congenital strabismus, sensory adaptations occur hampering the
      correct development of normal binocular vision. The aim of this study is to
      investigate if patients with congenital or early onset exotropic or esotropic
      strabismus adopt different walking strategies with respect to healthy subjects.
      Our hypothesis is that the abnormal binocular cooperation, occurring in patients
      with exotropic or esotropic strabismus, could influence neurosensorial adaptation
      of the gait pattern. MATERIALS AND METHODS: Twenty-five patients were enrolled:
      19 with esotropic (ESO) and 6 with exotropic strabismus (EXO). All patients
      underwent an ophthalmological and orthoptic evaluation. Biomechanical data were
      collected using a stereophotogrammetric system and a force platform. Twenty-seven
      age-matched healthy subjects (HS) were used as controls. RESULTS: The comparison
      between patients with ESO and patients with EXO strabismus showed that the
      maximal power at the knee and at the ankle was lower in EXO group (p < 0.01 and p
      < 0.05, respectively). The step width was statistically different between ESO and
      EXO groups (p < 0.01), lower in patients with ESO and higher in patients with EXO
      strabismus when compared with HS (though not statistically significant). The
      deviation angle values showed a relationship with the step width (at the near
      fixation p < 0.05) and with the maximal power at the knee and at the ankle (at
      the far fixation for the knee p < 0.001 and for the ankle p < 0.05; at the near
      fixation for the knee p < 0.05): in the patients with EXO the increased angle
      deviation is related to larger step width and to lower power at the knee and at
      the ankle. In the patients with ESO strabismus this relationship is less robust.
      DISCUSSION: Patients with EXO and ESO strabismus adopt different strategies to
      compensate their walking difficulties, and these strategies are likely due to an
      expanded binocular visual field in patients with EXO and to a reduced visual
      field in patients with ESO strabismus.

PMID- 25071515
TI  - EEG beta suppression and low gamma modulation are different elements of human
      upright walking.
AB  - Cortical involvement during upright walking is not well-studied in humans. We
      analyzed non-invasive electroencephalographic (EEG) recordings from able-bodied
      volunteers who participated in a robot-assisted gait-training experiment. To
      enable functional neuroimaging during walking, we applied source modeling to high
      density (120 channels) EEG recordings using individual anatomy reconstructed from
      structural magnetic resonance imaging scans. First, we analyzed amplitude
      differences between the conditions, walking and upright standing. Second, we
      investigated amplitude modulations related to the gait phase. During active
      walking upper MU (10-12 Hz) and beta (18-30 Hz) oscillations were suppressed
      [event-related desynchronization (ERD)] compared to upright standing. Significant
      beta ERD activity was located focally in central sensorimotor areas for 9/10
      subjects. Additionally, we found that low gamma (24-40 Hz) amplitudes were
      modulated related to the gait phase. Because there is a certain frequency band
      overlap between sustained beta ERD and gait phase related modulations in the low
      gamma range, these two phenomena are superimposed. Thus, we observe gait phase
      related amplitude modulations at a certain ERD level. We conclude that sustained
      MU and beta ERD reflect a movement related state change of cortical excitability
      while gait phase related modulations in the low gamma represent the motion
      sequence timing during gait. Interestingly, the center frequencies of sustained
      beta ERD and gait phase modulated amplitudes were identified to be different.
      They may therefore be caused by different neuronal rhythms, which should be taken
      under consideration in future studies. 

PMID- 25071516
TI  - "I am resting but rest less well with you." The moderating effect of anxious
      attachment style on alpha power during EEG resting state in a social context.
AB  - We took EEG recordings to measure task-free resting-state cortical brain activity
      in 35 participants under two conditions, alone (A) or together (T). We also
      investigated whether psychological attachment styles shape human cortical
      activity differently in these two settings. The results indicate that social
      context matters and that participants' cortical activity is moderated by the
      anxious, but not avoidant attachment style. We found enhanced alpha, beta and
      theta band activity in the T rather than the A resting-state condition, which was
      more pronounced in posterior brain regions. We further found a positive
      correlation between anxious attachment style and enhanced alpha power in the T
      vs. A condition over frontal and parietal scalp regions. There was no significant
      correlation between the absolute powers registered in the other two frequency
      bands and the participants' anxious attachment style. 

PMID- 25071518
TI  - Music lessons improve auditory perceptual and cognitive performance in deaf
      children.
AB  - Despite advanced technologies in auditory rehabilitation of profound deafness,
      deaf children often exhibit delayed cognitive and linguistic development and
      auditory training remains a crucial element of their education. In the present
      cross-sectional study, we assess whether music would be a relevant tool for deaf
      children rehabilitation. In normal-hearing children, music lessons have been
      shown to improve cognitive and linguistic-related abilities, such as phonetic
      discrimination and reading. We compared auditory perception, auditory cognition,
      and phonetic discrimination between 14 profoundly deaf children who completed
      weekly music lessons for a period of 1.5-4 years and 14 deaf children who did not
      receive musical instruction. Children were assessed on perceptual and cognitive
      auditory tasks using environmental sounds: discrimination, identification,
      auditory scene analysis, auditory working memory. Transfer to the linguistic
      domain was tested with a phonetic discrimination task. Musically trained children
      showed better performance in auditory scene analysis, auditory working memory and
      phonetic discrimination tasks, and multiple regressions showed that success on
      these tasks was at least partly driven by music lessons. We propose that musical
      education contributes to development of general processes such as auditory
      attention and perception, which, in turn, facilitate auditory-related cognitive
      and linguistic processes. 

PMID- 25071519
TI  - From episodic to habitual prospective memory: ERP-evidence for a linear
      transition.
AB  - Performing a prospective memory task repeatedly changes the nature of the task
      from episodic to habitual. The goal of the present study was to investigate the
      neural basis of this transition. In two experiments, we contrasted event-related
      potentials (ERPs) evoked by correct responses to prospective memory targets in
      the first, more episodic part of the experiment with those of the second, more
      habitual part of the experiment. Specifically, we tested whether the early,
      middle, or late ERP-components, which are thought to reflect cue detection,
      retrieval of the intention, and post-retrieval processes, respectively, would be
      changed by routinely performing the prospective memory task. The results showed a
      differential ERP effect in the middle time window (450-650 ms post-stimulus).
      Source localization using low resolution brain electromagnetic tomography
      analysis suggests that the transition was accompanied by an increase of
      activation in the posterior parietal and occipital cortex. These findings
      indicate that habitual prospective memory involves retrieval processes guided
      more strongly by parietal brain structures. In brief, the study demonstrates that
      episodic and habitual prospective memory tasks recruit different brain areas. 

PMID- 25071520
TI  - Attention, predictions and expectations, and their violation: attentional control
      in the human brain.

PMID- 25071521
TI  - Sequencing at the syllabic and supra-syllabic levels during speech perception: an
      fMRI study.
AB  - The processing of fluent speech involves complex computational steps that begin
      with the segmentation of the continuous flow of speech sounds into syllables and
      words. One question that naturally arises pertains to the type of syllabic
      information that speech processes act upon. Here, we used functional magnetic
      resonance imaging to profile regions, using a combination of whole-brain and
      exploratory anatomical region-of-interest (ROI) approaches, that were sensitive
      to syllabic information during speech perception by parametrically manipulating
      syllabic complexity along two dimensions: (1) individual syllable complexity, and
      (2) sequence complexity (supra-syllabic). We manipulated the complexity of the
      syllable by using the simplest syllable template-a consonant and vowel (CV)-and
      inserting an additional consonant to create a complex onset (CCV). The supra
      syllabic complexity was manipulated by creating sequences composed of the same
      syllable repeated six times (e.g., /pa-pa-pa-pa-pa-pa/) and sequences of three
      different syllables each repeated twice (e.g., /pa-ta-ka-pa-ta-ka/). This
      parametrical design allowed us to identify brain regions sensitive to (1)
      syllabic complexity independent of supra-syllabic complexity, (2) supra-syllabic
      complexity independent of syllabic complexity and, (3) both syllabic and supra
      syllabic complexity. High-resolution scans were acquired for 15 healthy adults.
      An exploratory anatomical ROI analysis of the supratemporal plane (STP)
      identified bilateral regions within the anterior two-third of the planum
      temporale, the primary auditory cortices as well as the anterior two-third of the
      superior temporal gyrus that showed different patterns of sensitivity to syllabic
      and supra-syllabic information. These findings demonstrate that during passive
      listening of syllable sequences, sublexical information is processed
      automatically, and sensitivity to syllabic and supra-syllabic information is
      localized almost exclusively within the STP. 

PMID- 25071522
TI  - Musically cued gait-training improves both perceptual and motor timing in
      Parkinson's disease.
AB  - It is well established that auditory cueing improves gait in patients with
      idiopathic Parkinson's disease (IPD). Disease-related reductions in speed and
      step length can be improved by providing rhythmical auditory cues via a metronome
      or music. However, effects on cognitive aspects of motor control have yet to be
      thoroughly investigated. If synchronization of movement to an auditory cue relies
      on a supramodal timing system involved in perceptual, motor, and sensorimotor
      integration, auditory cueing can be expected to affect both motor and perceptual
      timing. Here, we tested this hypothesis by assessing perceptual and motor timing
      in 15 IPD patients before and after a 4-week music training program with rhythmic
      auditory cueing. Long-term effects were assessed 1 month after the end of the
      training. Perceptual and motor timing was evaluated with a battery for the
      assessment of auditory sensorimotor and timing abilities and compared to that of
      age-, gender-, and education-matched healthy controls. Prior to training, IPD
      patients exhibited impaired perceptual and motor timing. Training improved
      patients' performance in tasks requiring synchronization with isochronous
      sequences, and enhanced their ability to adapt to durational changes in a
      sequence in hand tapping tasks. Benefits of cueing extended to time perception
      (duration discrimination and detection of misaligned beats in musical excerpts).
      The current results demonstrate that auditory cueing leads to benefits beyond
      gait and support the idea that coupling gait to rhythmic auditory cues in IPD
      patients relies on a neuronal network engaged in both perceptual and motor
      timing. 

PMID- 25071523
TI  - In your face: transcendence in embodied interaction.
AB  - In cognitive psychology, studies concerning the face tend to focus on questions
      about face recognition, theory of mind (ToM) and empathy. Questions about the
      face, however, also fit into a very different set of issues that are central to
      ethics. Based especially on the work of Levinas, philosophers have come to see
      that reference to the face of another person can anchor conceptions of moral
      responsibility and ethical demand. Levinas points to a certain irreducibility and
      transcendence implicit in the face of the other. In this paper I argue that the
      notion of transcendence involved in this kind of analysis can be given a
      naturalistic interpretation by drawing on recent interactive approaches to social
      cognition found in developmental psychology, phenomenology, and the study of
      autism. 

PMID- 25071524
TI  - Melodic multi-feature paradigm reveals auditory profiles in music-sound encoding.
AB  - Musical expertise modulates preattentive neural sound discrimination. However,
      this evidence up to great extent originates from paradigms using very simple
      stimulation. Here we use a novel melody paradigm (revealing the auditory profile
      for six sound parameters in parallel) to compare memory-related mismatch
      negativity (MMN) and attention-related P3a responses recorded from non-musicians
      and Finnish Folk musicians. MMN emerged in both groups of participants for all
      sound changes (except for rhythmic changes in non-musicians). In Folk musicians,
      the MMN was enlarged for mistuned sounds when compared with non-musicians. This
      is taken to reflect their familiarity with pitch information which is in key
      position in Finnish folk music when compared with e.g., rhythmic information. The
      MMN was followed by P3a after timbre changes, rhythm changes, and melody
      transposition. The MMN and P3a topographies differentiated the groups for all
      sound changes. Thus, the melody paradigm offers a fast and cost-effective means
      for determining the auditory profile for music-sound encoding and also,
      importantly, for probing the effects of musical expertise on it. 

PMID- 25071525
TI  - Evolution and development of interhemispheric connections in the vertebrate
      forebrain.
AB  - Axonal connections between the left and right sides of the brain are crucial for
      bilateral integration of lateralized sensory, motor, and associative functions.
      Throughout vertebrate species, forebrain commissures share a conserved
      developmental plan, a similar position relative to each other within the brain
      and similar patterns of connectivity. However, major events in the evolution of
      the vertebrate brain, such as the expansion of the telencephalon in tetrapods and
      the origin of the six-layered isocortex in mammals, resulted in the emergence and
      diversification of new commissural routes. These new interhemispheric connections
      include the pallial commissure, which appeared in the ancestors of tetrapods and
      connects the left and right sides of the medial pallium (hippocampus in mammals),
      and the corpus callosum, which is exclusive to eutherian (placental) mammals and
      connects both isocortical hemispheres. A comparative analysis of commissural
      systems in vertebrates reveals that the emergence of new commissural routes may
      have involved co-option of developmental mechanisms and anatomical substrates of
      preexistent commissural pathways. One of the embryonic regions of interest for
      studying these processes is the commissural plate, a portion of the early
      telencephalic midline that provides molecular specification and a cellular
      scaffold for the development of commissural axons. Further investigations into
      these embryonic processes in carefully selected species will provide insights not
      only into the mechanisms driving commissural evolution, but also regarding more
      general biological problems such as the role of developmental plasticity in
      evolutionary change. 

PMID- 25071526
TI  - Revisiting the continuum hypothesis: toward an in-depth exploration of executive
      functions in korsakoff syndrome.
AB  - Korsakoff syndrome (KS) is a neurological state mostly caused by alcohol
      dependence and leading to disproportionate episodic memory deficits. KS patients
      present more severe anterograde amnesia than Alcohol-Dependent Subjects (ADS),
      which led to the continuum hypothesis postulating a progressive increase in brain
      and cognitive damages during the evolution from ADS to KS. This hypothesis has
      been extensively examined for memory but is still debated for other abilities,
      notably executive functions (EF). EF have up to now been explored by unspecific
      tasks in KS, and few studies explored their interactions with memory. Exploring
      EF in KS by specific tasks based on current EF models could thus renew the
      exploration of the continuum hypothesis. This paper will propose a research
      program aiming at: (1) clarifying the extent of executive dysfunctions in KS by
      tasks focusing on specific EF subcomponents; (2) determining the differential EF
      deficits in ADS and KS; (3) exploring EF-memory interactions in KS with
      innovative tasks. At the fundamental level, this exploration will test the
      continuum hypothesis beyond memory. At the clinical level, it will propose new
      rehabilitation tools focusing on the EF specifically impaired in KS. 

PMID- 25071527
TI  - On the definition and interpretation of voice selective activation in the
      temporal cortex.
AB  - Regions along the superior temporal sulci and in the anterior temporal lobes have
      been found to be involved in voice processing. It has even been argued that parts
      of the temporal cortices serve as voice-selective areas. Yet, evidence for voice
      selective activation in the strict sense is still missing. The current fMRI study
      aimed at assessing the degree of voice-specific processing in different parts of
      the superior and middle temporal cortices. To this end, voices of famous persons
      were contrasted with widely different categories, which were sounds of animals
      and musical instruments. The argumentation was that only brain regions with
      statistically proven absence of activation by the control stimuli may be
      considered as candidates for voice-selective areas. Neural activity was found to
      be stronger in response to human voices in all analyzed parts of the temporal
      lobes except for the middle and posterior STG. More importantly, the activation
      differences between voices and the other environmental sounds increased
      continuously from the mid-posterior STG to the anterior MTG. Here, only voices
      but not the control stimuli excited an increase of the BOLD response above a
      resting baseline level. The findings are discussed with reference to the function
      of the anterior temporal lobes in person recognition and the general question on
      how to define selectivity of brain regions for a specific class of stimuli or
      tasks. In addition, our results corroborate recent assumptions about the
      hierarchical organization of auditory processing building on a processing stream
      from the primary auditory cortices to anterior portions of the temporal lobes. 

PMID- 25071528
TI  - Resting alpha activity predicts learning ability in alpha neurofeedback.
AB  - Individuals differ in their ability to learn how to regulate the brain activity
      by neurofeedback. This study aimed to investigate whether the resting alpha
      activity can predict the learning ability in alpha neurofeedback. A total of 25
      subjects performed 20 sessions of individualized alpha neurofeedback and the
      learning ability was assessed by three indices respectively: the training
      parameter changes between two periods, within a short period and across the whole
      training time. It was found that the resting alpha amplitude measured before
      training had significant positive correlations with all learning indices and
      could be used as a predictor for the learning ability prediction. This finding
      would help the researchers in not only predicting the training efficacy in
      individuals but also gaining further insight into the mechanisms of alpha
      neurofeedback. 

PMID- 25071529
TI  - MicroRNA-138 is a potential regulator of memory performance in humans.
AB  - Genetic factors underlie a substantial proportion of individual differences in
      cognitive functions in humans, including processes related to episodic and
      working memory. While genetic association studies have proposed several candidate
      "memory genes," these currently explain only a minor fraction of the phenotypic
      variance. Here, we performed genome-wide screening on 13 episodic and working
      memory phenotypes in 1318 participants of the Berlin Aging Study II aged 60 years
      or older. The analyses highlight a number of novel single nucleotide
      polymorphisms (SNPs) associated with memory performance, including one located in
      a putative regulatory region of microRNA (miRNA) hsa-mir-138-5p (rs9882688, P
      value = 7.8 * 10(-9)). Expression quantitative trait locus analyses on next
      generation RNA-sequencing data revealed that rs9882688 genotypes show a
      significant correlation with the expression levels of this miRNA in 309 human
      lymphoblastoid cell lines (P-value = 5 * 10(-4)). In silico modeling of other top
      ranking GWAS signals identified an additional memory-associated SNP in the 3'
      untranslated region (3' UTR) of DCP1B, a gene encoding a core component of the
      mRNA decapping complex in humans, predicted to interfere with hsa-mir-138-5p
      binding. This prediction was confirmed in vitro by luciferase assays showing
      differential binding of hsa-mir-138-5p to 3' UTR reporter constructs in two human
      cell lines (HEK293: P-value = 0.0470; SH-SY5Y: P-value = 0.0866). Finally,
      expression profiling of hsa-mir-138-5p and DCP1B mRNA in human post-mortem brain
      tissue revealed that both molecules are expressed simultaneously in frontal
      cortex and hippocampus, suggesting that the proposed interaction between hsa-mir
      138-5p and DCP1B may also take place in vivo. In summary, by combining unbiased
      genome-wide screening with extensive in silico modeling, in vitro functional
      assays, and gene expression profiling, our study identified miRNA-138 as a
      potential molecular regulator of human memory function. 

PMID- 25071530
TI  - Amplitude differences in high-frequency fMRI signals between eyes open and eyes
      closed resting states.
AB  - Recent studies employing rapid sampling techniques have demonstrated that the
      resting state fMRI (rs-fMRI) signal exhibits synchronized activities at
      frequencies much higher than the conventional frequency range (<0.1 Hz). However,
      little work has investigated the changes in the high-frequency fluctuations
      between different resting states. Here, we acquired rs-fMRI data at a high
      sampling rate (TR = 400 ms) from subjects with both eyes open (EO) and eyes
      closed (EC), and compared the amplitude of fluctuation (AF) between EO and EC for
      both the low- and high-frequency components. In addition to robust AF differences
      in the conventional low frequency band (<0.1 Hz) in visual cortex, primary
      auditory cortex and primary sensorimotor cortex (PSMC), we also detected high
      frequency (primarily in 0.1-0.35 Hz) differences. The high-frequency results
      without covariates regression exhibited noisy patterns. For the data with
      nuisance covariates regression, we found a significant and reproducible reduction
      in high-frequency AF between EO and EC in the bilateral PSMC and the
      supplementary motor area (SMA), and an increase in high-frequency AF in the left
      middle occipital gyrus (MOG). Furthermore, we investigated the effect of sampling
      rate by down-sampling the data to effective TR = 2 s. Briefly, by using the rapid
      sampling rate, we were able to detect more regions with significant differences
      while identifying fewer artifactual differences in the high-frequency bands as
      compared to the down-sampled dataset. We concluded that (1) high-frequency
      fluctuations of rs-fMRI signals can be modulated by different resting states and
      thus may be of physiological importance; and (2) the regression of covariates and
      the use of fast sampling rates are superior for revealing high-frequency
      differences in rs-fMRI signals. 

PMID- 25071531
TI  - Interference of tonic muscle activity on the EEG: a single motor unit study.
AB  - The electrical activity of muscles can interfere with the electroencephalogram
      (EEG) signal considering the anatomical locations of facial or masticatory
      muscles surrounding the skull. In this study, we evaluated the possible
      interference of the resting activity of the temporalis muscle on the EEG under
      conventional EEG recording conditions. In 9 healthy adults EEG activity from 19
      scalp locations and single motor unit (SMU) activity from anterior temporalis
      muscle were recorded in three relaxed conditions; eyes open, eyes closed, jaw
      dropped. The EEG signal was spike triggered averaged (STA) using the action
      potentials of SMUs as triggers to evaluate their reflections at various EEG
      recording sites. Resting temporalis SMU activity generated prominent reflections
      with different amplitudes, reaching maxima in the proximity of the recorded SMU.
      Interference was also notable at the scalp sites that are relatively far from the
      recorded SMU and even at the contralateral locations. Considering the great
      number of SMUs in the head and neck muscles, prominent contamination from the
      activity of only a single MU should indicate the susceptibility of EEG to muscle
      activity artifacts even under the rest conditions. This study emphasizes the need
      for efficient artifact evaluation methods which can handle muscle interferences. 

PMID- 25071532
TI  - When mirroring is both simple and "smart": how mimicry can be embodied, adaptive,
      and non-representational.
AB  - The concept of mirroring has become rather ubiquitous. One of the most
      fundamental empirical and theoretical debates within research on mirroring
      concerns the role of mental representations: while some models argue that higher
      order representational mechanisms underpin most cases of mirroring, other models
      argue that they only moderate a primarily non-representational process. As such,
      even though research on mirroring-along with its neural substrates, including the
      putative mirror neuron system-has grown tremendously, so too has confusion about
      what it actually means to "mirror". Using recent research on spontaneous
      imitation, we argue that flexible mirroring effects can be fully embodied and
      dynamic-even in the absence of higher-order mental representations. We propose
      that mirroring can simply reflect an adaptive integration and utilization of cues
      obtained from the brain, body, and environment, which is especially evident
      within the social context. Such a view offers reconciliation among both
      representational and non-representational frameworks in cognitive neuroscience,
      which will facilitate revised interpretations of modern (and seemingly divergent)
      findings on when and how these embodied mirroring responses are employed. 

PMID- 25071533
TI  - Investigating the contribution of ventral-lexical and dorsal-sublexical pathways
      during reading in bilinguals.
AB  - Several studies suggest the existence of ventral-lexical and dorsal-sublexical
      systems for reading. The relative contribution of these pathways can be
      manipulated by stimulus type and task demands. However, little is known about how
      bilinguals use these systems to read in their second language. In this study
      diffusion tensor imaging (DTI) was used to investigate the relationship between
      white matter (WM) integrity and reaction time in a group of 12 Chinese-English
      bilingual and 11 age-matched English monolingual adults. Considering a dual-route
      model of reading, the following four tracts were isolated in both the left and
      right hemispheres using a tractography measurement approach. Ventral tracts
      included the uncinate fasciculus (UF) and the inferior longitudinal fasciculus
      (ILF). The dorsal tracts of interest were the arcuate fasciculus (AF) and the
      superior longitudinal fasciculus (SLF). A significant correlation between the
      reaction time in a reading task and the mean diffusivity (MD) value was observed
      in the right UF in both bilingual and monolingual groups. Moreover, in the
      bilingual group we observed significantly more positive relationships between
      reaction time and MD in the right AF, and bilaterally in the SLF. We concluded
      that the relative contribution of the dorsal system for reading is greater in
      bilinguals than monolinguals. Further, these findings implicate a role of the
      right hemisphere in reading. 

PMID- 25071534
TI  - Rigidity, chaos and integration: hemispheric interaction and individual
      differences in metaphor comprehension.
AB  - Neurotypical individuals cope flexibly with the full range of semantic relations
      expressed in human language, including metaphoric relations. This impressive
      semantic ability may be associated with distinct and flexible patterns of
      hemispheric interaction, including higher right hemisphere (RH) involvement for
      processing novel metaphors. However, this ability may be impaired in specific
      clinical conditions, such as Asperger syndrome (AS) and schizophrenia. The
      impaired semantic processing is accompanied by different patterns of hemispheric
      interaction during semantic processing, showing either reduced (in Asperger
      syndrome) or excessive (in schizophrenia) RH involvement. This paper interprets
      these individual differences using the terms Rigidity, Chaos and Integration,
      which describe patterns of semantic memory network states that either lead to
      semantic well-being or are disruptive of it. We argue that these semantic network
      states lie on a rigidity-chaos semantic continuum. We define these terms via
      network science terminology and provide network, cognitive and neural evidence to
      support our claim. This continuum includes left hemisphere (LH) hyper-rigid
      semantic memory state on one end (e.g., in persons with AS), and RH chaotic and
      over-flexible semantic memory state on the other end (e.g., in persons with
      schizophrenia). In between these two extremes lie different states of semantic
      memory structure which are related to individual differences in semantic
      creativity. We suggest that efficient semantic processing is achieved by semantic
      integration, a balance between semantic rigidity and semantic chaos. Such
      integration is achieved via intra-hemispheric communication. However, impairments
      to this well-balanced and integrated pattern of hemispheric interaction, e.g.,
      when one hemisphere dominates the other, may lead to either semantic rigidity or
      semantic chaos, moving away from semantic integration and thus impairing the
      processing of metaphoric language. 

PMID- 25071535
TI  - Feature-based attentional modulation of orientation perception in
      somatosensation.
AB  - In a reaction time study of human tactile orientation detection the effects of
      spatial attention and feature-based attention were investigated. Subjects had to
      give speeded responses to target orientations (parallel and orthogonal to the
      finger axis) in a random stream of oblique tactile distractor orientations
      presented to their index and ring fingers. Before each block of trials, subjects
      received a tactile cue at one finger. By manipulating the validity of this cue
      with respect to its location and orientation (feature), we provided an incentive
      to subjects to attend spatially to the cued location and only there to the cued
      orientation. Subjects showed quicker responses to parallel compared to orthogonal
      targets, pointing to an orientation anisotropy in sensory processing. Also,
      faster reaction times (RTs) were observed in location-matched trials, i.e., when
      targets appeared on the cued finger, representing a perceptual benefit of spatial
      attention. Most importantly, RTs were shorter to orientations matching the cue,
      both at the cued and at the uncued location, documenting a global enhancement of
      tactile sensation by feature-based attention. This is the first report of a
      perceptual benefit of feature-based attention outside the spatial focus of
      attention in somatosensory perception. The similarity to effects of feature-based
      attention in visual perception supports the notion of matching attentional
      mechanisms across sensory domains. 

PMID- 25071536
TI  - Memory consolidation from seconds to weeks: a three-stage neural network model
      with autonomous reinstatement dynamics.
AB  - Declarative long-term memories are not created in an instant. Gradual
      stabilization and temporally shifting dependence of acquired declarative memories
      in different brain regions-called systems consolidation-can be tracked in time by
      lesion experiments. The observation of temporally graded retrograde amnesia (RA)
      following hippocampal lesions points to a gradual transfer of memory from
      hippocampus to neocortical long-term memory. Spontaneous reactivations of
      hippocampal memories, as observed in place cell reactivations during slow-wave
      sleep, are supposed to drive neocortical reinstatements and facilitate this
      process. We propose a functional neural network implementation of these ideas and
      furthermore suggest an extended three-state framework that includes the
      prefrontal cortex (PFC). It bridges the temporal chasm between working memory
      percepts on the scale of seconds and consolidated long-term memory on the scale
      of weeks or months. We show that our three-stage model can autonomously produce
      the necessary stochastic reactivation dynamics for successful episodic memory
      consolidation. The resulting learning system is shown to exhibit classical memory
      effects seen in experimental studies, such as retrograde and anterograde amnesia
      (AA) after simulated hippocampal lesioning; furthermore the model reproduces
      peculiar biological findings on memory modulation, such as retrograde
      facilitation of memory after suppressed acquisition of new long-term memories
      similar to the effects of benzodiazepines on memory. 

PMID- 25071537
TI  - Robust development of synfire chains from multiple plasticity mechanisms.
AB  - Biological neural networks are shaped by a large number of plasticity mechanisms
      operating at different time scales. How these mechanisms work together to sculpt
      such networks into effective information processing circuits is still poorly
      understood. Here we study the spontaneous development of synfire chains in a self
      organizing recurrent neural network (SORN) model that combines a number of
      different plasticity mechanisms including spike-timing-dependent plasticity,
      structural plasticity, as well as homeostatic forms of plasticity. We find that
      the network develops an abundance of feed-forward motifs giving rise to synfire
      chains. The chains develop into ring-like structures, which we refer to as
      "synfire rings." These rings emerge spontaneously in the SORN network and allow
      for stable propagation of activity on a fast time scale. A single network can
      contain multiple non-overlapping rings suppressing each other. On a slower time
      scale activity switches from one synfire ring to another maintaining firing rate
      homeostasis. Overall, our results show how the interaction of multiple plasticity
      mechanisms might give rise to the robust formation of synfire chains in
      biological neural networks. 

PMID- 25071538
TI  - Learning and stabilization of winner-take-all dynamics through interacting
      excitatory and inhibitory plasticity.
AB  - Winner-Take-All (WTA) networks are recurrently connected populations of
      excitatory and inhibitory neurons that represent promising candidate
      microcircuits for implementing cortical computation. WTAs can perform powerful
      computations, ranging from signal-restoration to state-dependent processing.
      However, such networks require fine-tuned connectivity parameters to keep the
      network dynamics within stable operating regimes. In this article, we show how
      such stability can emerge autonomously through an interaction of biologically
      plausible plasticity mechanisms that operate simultaneously on all excitatory and
      inhibitory synapses of the network. A weight-dependent plasticity rule is derived
      from the triplet spike-timing dependent plasticity model, and its stabilization
      properties in the mean-field case are analyzed using contraction theory. Our main
      result provides simple constraints on the plasticity rule parameters, rather than
      on the weights themselves, which guarantee stable WTA behavior. The plastic
      network we present is able to adapt to changing input conditions, and to
      dynamically adjust its gain, therefore exhibiting self-stabilization mechanisms
      that are crucial for maintaining stable operation in large networks of
      interconnected subunits. We show how distributed neural assemblies can adjust
      their parameters for stable WTA function autonomously while respecting anatomical
      constraints on neural wiring. 

PMID- 25071539
TI  - A general role for medial prefrontal cortex in event prediction.
AB  - A recent computational neural model of medial prefrontal cortex (mPFC), namely
      the predicted response-outcome (PRO) model (Alexander and Brown, 2011), suggests
      that mPFC learns to predict the outcomes of actions. The model accounted for a
      wide range of data on the mPFC. Nevertheless, numerous recent findings suggest
      that mPFC may signal predictions and prediction errors even when the predicted
      outcomes are not contingent on prior actions. Here we show that the existing PRO
      model can learn to predict outcomes in a general sense, and not only when the
      outcomes are contingent on actions. A series of simulations show how this
      generalized PRO model can account for an even broader range of findings in the
      mPFC, including human ERP, fMRI, and macaque single-unit data. The results
      suggest that the mPFC learns to predict salient events in general and provides a
      theoretical framework that links mPFC function to model-based reinforcement
      learning, Bayesian learning, and theories of cognitive control. 

PMID- 25071540
TI  - A flexible, interactive software tool for fitting the parameters of neuronal
      models.
AB  - The construction of biologically relevant neuronal models as well as model-based
      analysis of experimental data often requires the simultaneous fitting of multiple
      model parameters, so that the behavior of the model in a certain paradigm matches
      (as closely as possible) the corresponding output of a real neuron according to
      some predefined criterion. Although the task of model optimization is often
      computationally hard, and the quality of the results depends heavily on technical
      issues such as the appropriate choice (and implementation) of cost functions and
      optimization algorithms, no existing program provides access to the best
      available methods while also guiding the user through the process effectively.
      Our software, called Optimizer, implements a modular and extensible framework for
      the optimization of neuronal models, and also features a graphical interface
      which makes it easy for even non-expert users to handle many commonly occurring
      scenarios. Meanwhile, educated users can extend the capabilities of the program
      and customize it according to their needs with relatively little effort.
      Optimizer has been developed in Python, takes advantage of open-source Python
      modules for nonlinear optimization, and interfaces directly with the NEURON
      simulator to run the models. Other simulators are supported through an external
      interface. We have tested the program on several different types of problems of
      varying complexity, using different model classes. As targets, we used simulated
      traces from the same or a more complex model class, as well as experimental data.
      We successfully used Optimizer to determine passive parameters and conductance
      densities in compartmental models, and to fit simple (adaptive exponential
      integrate-and-fire) neuronal models to complex biological data. Our detailed
      comparisons show that Optimizer can handle a wider range of problems, and
      delivers equally good or better performance than any other existing neuronal
      model fitting tool. 

PMID- 25071541
TI  - Algorithms of causal inference for the analysis of effective connectivity among
      brain regions.
AB  - In recent years, powerful general algorithms of causal inference have been
      developed. In particular, in the framework of Pearl's causality, algorithms of
      inductive causation (IC and IC(*)) provide a procedure to determine which causal
      connections among nodes in a network can be inferred from empirical observations
      even in the presence of latent variables, indicating the limits of what can be
      learned without active manipulation of the system. These algorithms can in
      principle become important complements to established techniques such as Granger
      causality and Dynamic Causal Modeling (DCM) to analyze causal influences
      (effective connectivity) among brain regions. However, their application to
      dynamic processes has not been yet examined. Here we study how to apply these
      algorithms to time-varying signals such as electrophysiological or neuroimaging
      signals. We propose a new algorithm which combines the basic principles of the
      previous algorithms with Granger causality to obtain a representation of the
      causal relations suited to dynamic processes. Furthermore, we use graphical
      criteria to predict dynamic statistical dependencies between the signals from the
      causal structure. We show how some problems for causal inference from neural
      signals (e.g., measurement noise, hemodynamic responses, and time aggregation)
      can be understood in a general graphical approach. Focusing on the effect of
      spatial aggregation, we show that when causal inference is performed at a coarser
      scale than the one at which the neural sources interact, results strongly depend
      on the degree of integration of the neural sources aggregated in the signals, and
      thus characterize more the intra-areal properties than the interactions among
      regions. We finally discuss how the explicit consideration of latent processes
      contributes to understand Granger causality and DCM as well as to distinguish
      functional and effective connectivity. 

PMID- 25071542
TI  - Data dictionary services in XNAT and the Human Connectome Project.
AB  - The XNAT informatics platform is an open source data management tool used by
      biomedical imaging researchers around the world. An important feature of XNAT is
      its highly extensible architecture: users of XNAT can add new data types to the
      system to capture the imaging and phenotypic data generated in their studies.
      Until recently, XNAT has had limited capacity to broadcast the meaning of these
      data extensions to users, other XNAT installations, and other software. We have
      implemented a data dictionary service for XNAT, which is currently being used on
      ConnectomeDB, the Human Connectome Project (HCP) public data sharing website. The
      data dictionary service provides a framework to define key relationships between
      data elements and structures across the XNAT installation. This includes not just
      core data representing medical imaging data or subject or patient evaluations,
      but also taxonomical structures, security relationships, subject groups, and
      research protocols. The data dictionary allows users to define metadata for data
      structures and their properties, such as value types (e.g., textual, integers,
      floats) and valid value templates, ranges, or field lists. The service provides
      compatibility and integration with other research data management services by
      enabling easy migration of XNAT data to standards-based formats such as the
      Resource Description Framework (RDF), JavaScript Object Notation (JSON), and
      Extensible Markup Language (XML). It also facilitates the conversion of XNAT's
      native data schema into standard neuroimaging vocabularies and structures. 

PMID- 25071543
TI  - Brain-computer interface with somatosensory feedback improves functional recovery
      from severe hemiplegia due to chronic stroke.
AB  - Recent studies have shown that scalp electroencephalogram (EEG) based brain
      computer interface (BCI) has a great potential for motor rehabilitation in stroke
      patients with severe hemiplegia. However, key elements in BCI architecture for
      functional recovery has yet to be clear. We in this study focused on the type of
      feedback to the patients, which is given contingently to their motor-related EEG
      in a BCI context. The efficacy of visual and somatosensory feedbacks was compared
      by a two-group study with the chronic stroke patients who are suffering with
      severe motor hemiplegia. Twelve patients were asked an attempt of finger opening
      in the affected side repeatedly, and the event-related desynchronization (ERD) in
      EEG of alpha and beta rhythms was monitored over bilateral parietal regions. Six
      patients were received a simple visual feedback in which the hand open/grasp
      picture on screen was animated at eye level, following significant ERD. Six
      patients were received a somatosensory feedback in which the motor-driven
      orthosis was triggered to extend the paralyzed fingers from 90 to 50 degrees .
      All the participants received 1-h BCI treatment with 12-20 training days. After
      the training period, while no changes in clinical scores and electromyographic
      (EMG) activity were observed in visual feedback group after training, voluntary
      EMG activity was newly observed in the affected finger extensors in four cases
      and the clinical score of upper limb function in the affected side was also
      improved in three participants in somatosensory feedback group. Although the
      present study was conducted with a limited number of patients, these results
      imply that BCI training with somatosensory feedback could be more effective for
      rehabilitation than with visual feedback. This pilot trial positively encouraged
      further clinical BCI research using a controlled design. 

PMID- 25071544
TI  - Exploration of the neural correlates of cerebral palsy for sensorimotor BCI
      control.
AB  - Cerebral palsy (CP) includes a broad range of disorders, which can result in
      impairment of posture and movement control. Brain-computer interfaces (BCIs) have
      been proposed as assistive devices for individuals with CP. Better understanding
      of the neural processing underlying motor control in affected individuals could
      lead to more targeted BCI rehabilitation and treatment options. We have explored
      well-known neural correlates of movement, including event-related
      desynchronization (ERD), phase synchrony, and a recently-introduced measure of
      phase dynamics, in participants with CP and healthy control participants.
      Although present, significantly less ERD and phase locking were found in the
      group with CP. Additionally, inter-group differences in phase dynamics were also
      significant. Taken together these findings suggest that users with CP exhibit
      lower levels of motor cortex activation during motor imagery, as reflected in
      lower levels of ongoing mu suppression and less functional connectivity. These
      differences indicate that development of BCIs for individuals with CP may pose
      additional challenges beyond those faced in providing BCIs to healthy
      individuals. 

PMID- 25071545
TI  - Brain-computer interface game applications for combined neurofeedback and
      biofeedback treatment for children on the autism spectrum.
AB  - Individuals with autism spectrum disorder (ASD) show deficits in social and
      communicative skills, including imitation, empathy, and shared attention, as well
      as restricted interests and repetitive patterns of behaviors. Evidence for and
      against the idea that dysfunctions in the mirror neuron system are involved in
      imitation and could be one underlying cause for ASD is discussed in this review.
      Neurofeedback interventions have reduced symptoms in children with ASD by self
      regulation of brain rhythms. However, cortical deficiencies are not the only
      cause of these symptoms. Peripheral physiological activity, such as the heart
      rate and its variability, is closely linked to neurophysiological signals and
      associated with social engagement. Therefore, a combined approach targeting the
      interplay between brain, body, and behavior could be more effective. Brain
      computer interface applications for combined neurofeedback and biofeedback
      treatment for children with ASD are currently nonexistent. To facilitate their
      use, we have designed an innovative game that includes social interactions and
      provides neural- and body-based feedback that corresponds directly to the
      underlying significance of the trained signals as well as to the behavior that is
      reinforced. 

PMID- 25071546
TI  - Tracking single units in chronic, large scale, neural recordings for brain
      machine interface applications.
AB  - In the study of population coding in neurobiological systems, tracking unit
      identity may be critical to assess possible changes in the coding properties of
      neuronal constituents over prolonged periods of time. Ensuring unit stability is
      even more critical for reliable neural decoding of motor variables in intra
      cortically controlled brain-machine interfaces (BMIs). Variability in intrinsic
      spike patterns, tuning characteristics, and single-unit identity over chronic use
      is a major challenge to maintaining this stability, requiring frequent daily
      calibration of neural decoders in BMI sessions by an experienced human operator.
      Here, we report on a unit-stability tracking algorithm that efficiently and
      autonomously identifies putative single-units that are stable across many
      sessions using a relatively short duration recording interval at the start of
      each session. The algorithm first builds a database of features extracted from
      units' average spike waveforms and firing patterns across many days of recording.
      It then uses these features to decide whether spike occurrences on the same
      channel on one day belong to the same unit recorded on another day or not. We
      assessed the overall performance of the algorithm for different choices of
      features and classifiers trained using human expert judgment, and quantified it
      as a function of accuracy and execution time. Overall, we found a trade-off
      between accuracy and execution time with increasing data volumes from chronically
      implanted rhesus macaques, with an average of 12 s processing time per channel at
      ~90% classification accuracy. Furthermore, 77% of the resulting putative single
      units matched those tracked by human experts. These results demonstrate that over
      the span of a few months of recordings, automated unit tracking can be performed
      with high accuracy and used to streamline the calibration phase during BMI
      sessions. Our findings may be useful to the study of population coding during
      learning, and to improve the reliability of BMI systems and accelerate their
      deployment in clinical applications. 

PMID- 25071547
TI  - Changes in functional connectivity correlate with behavioral gains in stroke
      patients after therapy using a brain-computer interface device.
AB  - Brain-computer interface (BCI) technology is being incorporated into new stroke
      rehabilitation devices, but little is known about brain changes associated with
      its use. We collected anatomical and functional MRI of nine stroke patients with
      persistent upper extremity motor impairment before, during, and after therapy
      using a BCI system. Subjects were asked to perform finger tapping of the impaired
      hand during fMRI. Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and
      Stroke Impact Scale (SIS) domains of Hand Function (HF) and Activities of Daily
      Living (ADL) were also assessed. Group-level analyses examined changes in whole
      brain task-based functional connectivity (FC) to seed regions in the motor
      network observed during and after BCI therapy. Whole-brain FC analyses seeded in
      each thalamus showed FC increases from baseline at mid-therapy and post-therapy
      (p < 0.05). Changes in FC between seeds at both the network and the connection
      levels were examined for correlations with changes in behavioral measures.
      Average motor network FC was increased post-therapy, and changes in average
      network FC correlated (p < 0.05) with changes in performance on ARAT (R (2) =
      0.21), 9-HPT (R (2) = 0.41), SIS HF (R (2) = 0.27), and SIS ADL (R (2) = 0.40).
      Multiple individual connections within the motor network were found to correlate
      in change from baseline with changes in behavioral measures. Many of these
      connections involved the thalamus, with change in each of four behavioral
      measures significantly correlating with change from baseline FC of at least one
      thalamic connection. These preliminary results show changes in FC that occur with
      the administration of rehabilitative therapy using a BCI system. The correlations
      noted between changes in FC measures and changes in behavioral outcomes indicate
      that both adaptive and maladaptive changes in FC may develop with this therapy
      and also suggest a brain-behavior relationship that may be stimulated by the
      neuromodulatory component of BCI therapy. 

PMID- 25071548
TI  - Reduced discomfort during high-definition transcutaneous stimulation using 6%
      benzocaine.
AB  - BACKGROUND: High-Definition transcranial Direct Current Stimulation (HD-tDCS)
      allows for non-invasive neuromodulation using an array of compact (approximately
      1 cm(2) contact area) "High-Definition" (HD) electrodes, as compared to
      conventional tDCS (which uses two large pads that are approximately 35 cm(2)). In
      a previous transcutaneous study, we developed and validated designs for HD
      electrodes that reduce discomfort over >20 min session with 2 mA electrode
      current. OBJECTIVE: The purpose of this study was to investigate the use of a
      chemical pretreatment with 6% benzocaine (topical numbing agent) to further
      reduce subjective discomfort during transcutaneous stimulation and to allow for
      better sham controlled studies. METHODS: Pre-treatment with 6% benzocaine was
      compared with control (no pretreatment) for 22 min 2 mA of stimulation, with
      either CCNY-4 or Lectron II electroconductive gel, for both cathodal and anodal
      transcutaneous (forearm) stimulation (eight different combinations). RESULTS:
      RESULTS show that for all conditions and polarities tested, stimulation with HD
      electrodes is safe and well tolerated and that pretreatment further reduced
      subjective discomfort. CONCLUSION: Pretreatment with a mild analgesic reduces
      discomfort during HD-tDCS.

PMID- 25071549
TI  - LTD expression is independent of glutamate receptor subtype.
AB  - Long-term depression (LTD) is a form of synaptic plasticity that plays a major
      role in the activity-dependent reshaping of synaptic transmission. LTD is
      expressed as a decrease in synaptic AMPA receptor number, though the exact
      mechanism remains controversial. Several lines of evidence have suggested
      necessary roles for both the GluA1 and GluA2 subunits, and specifically certain
      interactions with their cytoplasmic tails. However, it is unclear if either GluA1
      or GluA2 are absolutely required for LTD. We tested this hypothesis using
      constitutive knock-outs and single-cell molecular replacement of AMPA receptor
      subunits in mouse hippocampus. We found that neither GluA1 or GluA2 are required
      for normal expression of LTD, and indeed a normal decrease in synaptic
      transmission was observed in cells in which all endogenous AMPA receptors have
      been replaced by kainate receptors. Thus, LTD does not require removal of
      specific AMPA receptor subunits, but likely involves a more general modification
      of the synapse and its ability to anchor a broad range of receptor proteins. 

PMID- 25071550
TI  - Impaired generation of new subcategories and switching in a semantic verbal
      fluency test in older adults with mild cognitive impairment.
AB  - The semantic verbal fluency task is broadly used in the neuropsychological
      assessment of elderly subjects. Even some studies have identified differences in
      verbal fluency clustering and switching measures between subjects with normal
      aging and a clinical condition such as mild cognitive impairment (MCI) and
      Alzheimer's disease, the results are not always consistent. This study aimed to
      compare clustering and switching measures of an animal's semantic verbal fluency
      task among normal controls (NC, n = 25), amnestic mild cognitive impairment
      (aMCI; n = 25), amnestic multiple domain Mild Cognitive Impairment (a+mdMCI; n =
      25) and Alzheimer's disease (AD; n = 25) Brazilian subjects. The analyses were
      executed considering three (unifying the MCI subtypes) and four groups. As the
      data were not normally distributed, we carried out non-parametric tests (Kruskal
      Wallis and Mann-Whitney tests) to evaluate the differences in performance in the
      measures of the verbal fluency test among the groups. The comparison demonstrated
      that the groups differed in the total of correct words produced, number of
      clusters and switching but the measure of new subcategories was the only with
      significant difference among the NC and all the clinical groups. The measure of
      new subcategories is the number of original subcategories inside the higher
      category of animals that the subject produced, such as farm, domestic, African
      animals. Our results indicate that semantic memory impairment is a visible and
      recent deficit that occurs even in non-demented subjects with very MCI and the
      implications of these findings are discussed. 

PMID- 25071551
TI  - Correlations between Limbic White Matter and Cognitive Function in Temporal-Lobe
      Epilepsy, Preliminary Findings.
AB  - The limbic system is presumed to have a central role in cognitive performance, in
      particular memory. The purpose of this study was to investigate the relationship
      between limbic white matter microstructure and neuropsychological function in
      temporal-lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI).
      Twenty-one adult TLE patients, including 7 non-lesional (nlTLE) and 14 with
      unilateral mesial temporal sclerosis (uTLE), were studied with both DTI and
      hippocampal T2 relaxometry. Correlations were performed between fractional
      anisotropy (FA) of the bilateral fornix and cingulum, hippocampal T2,
      neuropsychological tests. Positive correlations were observed in the whole group
      for the left fornix and processing speed index. In contrast, memory tests did not
      show significant correlations with DTI findings. Subgroup analysis demonstrated
      an association between the left fornix and processing speed in nlTLE but not
      uTLE. No correlations were observed between hippocampal T2 and test scores in
      either the TLE group as a whole or after subgroup analysis. Our findings suggest
      that integrity of the left fornix specifically is an important anatomical
      correlate of cognitive function in TLE patients, in particular patients with
      nlTLE. 

PMID- 25071552
TI  - Copper: from neurotransmission to neuroproteostasis.
AB  - Copper is critical for the Central Nervous System (CNS) development and function.
      In particular, different studies have shown the effect of copper at brain
      synapses, where it inhibits Long Term Potentation (LTP) and receptor
      pharmacology. Paradoxically, according to recent studies copper is required for a
      normal LTP response. Copper is released at the synaptic cleft, where it blocks
      glutamate receptors, which explain its blocking effects on excitatory
      neurotransmission. Our results indicate that copper also enhances
      neurotransmission through the accumulation of PSD95 protein, which increase the
      levels of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors located at the plasma membrane of the post-synaptic density. Thus, our
      findings represent a novel mechanism for the action of copper, which may have
      implications for the neurophysiology and neuropathology of the CNS. These data
      indicate that synaptic configuration is sensitive to transient changes in
      transition metal homeostasis. Our results suggest that copper increases GluA1
      subunit levels of the AMPA receptor through the anchorage of AMPA receptors to
      the plasma membrane as a result of PSD-95 accumulation. Here, we will review the
      role of copper on neurotransmission of CNS neurons. In addition, we will discuss
      the potential mechanisms by which copper could modulate neuronal proteostasis
      ("neuroproteostasis") in the CNS with focus in the Ubiquitin Proteasome System
      (UPS), which is particularly relevant to neurological disorders such as
      Alzheimer's disease (AD) where copper and protein dyshomeostasis may contribute
      to neurodegeneration. An understanding of these mechanisms may ultimately lead to
      the development of novel therapeutic approaches to control metal and synaptic
      alterations observed in AD patients. 

PMID- 25071553
TI  - Increased visibility of deep medullary veins in leukoaraiosis: a 3-T MRI study.
AB  - Cerebral venous collagenosis has been implicated in leading to white matter
      hyperintensities (WMHs) via venous ischemia. We sought to determine whether
      cerebral venous dilation or ischemia correlate with the severity of WMHs by
      quantitative in vivo imaging techniques. This was an investigator-initiated
      prospective single-center study. We reviewed clinical, laboratory data from 158
      consecutive WMHs patients and 50 controls, and measured the number of voxels of
      deep medullary veins (DMVs) on susceptibility-weighted image and assessed the WMH
      volume (as a marker of the severity of WMHs) on a 3-T magnetic resonance system.
      We then performed the logistic-regression analysis and partial Pearson's
      correlation analysis to examine the association between the venous voxel count
      and WMH volume. The number of voxels of DMVs was significantly higher in WMHs
      than in controls. Increased number of voxels of DMVs was independently associated
      with both WMH volume of the whole brain and coregistered regional WMH volume
      after adjusting for age and number of lacunes. Our study indicates that cerebral
      deep venous insufficiency or ischemia play a role in the pathogenesis of WMHs,
      which may provide prognostic information on patients with WMHs and may have
      implications for therapeutic interventions. 

PMID- 25071554
TI  - Application of a MRI based index to longitudinal atrophy change in Alzheimer
      disease, mild cognitive impairment and healthy older individuals in the
      AddNeuroMed cohort.
AB  - Cross sectional studies of patients at risk of developing Alzheimer disease (AD)
      have identified several brain regions known to be prone to degeneration suitable
      as biomarkers, including hippocampal, ventricular, and whole brain volume. The
      aim of this study was to longitudinally evaluate an index based on morphometric
      measures derived from MRI data that could be used for classification of AD and
      healthy control subjects, as well as prediction of conversion from mild cognitive
      impairment (MCI) to AD. Patients originated from the AddNeuroMed project at
      baseline (119 AD, 119 MCI, 110 controls (CTL)) and 1-year follow-up (62 AD, 73
      MCI, 79 CTL). Data consisted of 3D T1-weighted MR images, demographics, MMSE,
      ADAS-Cog, CERAD and CDR scores, and APOE e4 status. We computed an index using a
      multivariate classification model (AD vs. CTL), using orthogonal partial least
      squares to latent structures (OPLS). Sensitivity, specificity and AUC were
      determined. Performance of the classifier (AD vs. CTL) was high at baseline (10
      fold cross-validation, 84% sensitivity, 91% specificity, 0.93 AUC) and at 1-year
      follow-up (92% sensitivity, 74% specificity, 0.93 AUC). Predictions of conversion
      from MCI to AD were good at baseline (77% of MCI converters) and at follow-up
      (91% of MCI converters). MCI carriers of the APOE e4 allele manifested more
      atrophy and presented a faster cognitive decline when compared to non-carriers.
      The derived index demonstrated a steady increase in atrophy over time, yielding
      higher accuracy in prediction at the time of clinical conversion.
      Neuropsychological tests appeared less sensitive to changes over time. However,
      taking the average of the two time points yielded better correlation between the
      index and cognitive scores as opposed to using cross-sectional data only. Thus,
      multivariate classification seemed to detect patterns of AD changes before
      conversion from MCI to AD and including longitudinal information is of great
      importance. 

PMID- 25071555
TI  - Differential behavioral and physiological effects of anodal transcranial direct
      current stimulation in healthy adults of younger and older age.
AB  - Changes in gamma-aminobutyric acid (GABA) mediated synaptic transmission have
      been associated with age-related motor and cognitive functional decline. Since
      anodal transcranial direct current stimulation (atDCS) has been suggested to
      target cortical GABAergic inhibitory interneurons, its potential for the
      treatment of deficient inhibitory activity and functional decline is being
      increasingly discussed. Therefore, after-effects of a single session of atDCS on
      resting-state and event-related short-interval intracortical inhibition (SICI) as
      evaluated with double-pulse TMS and dexterous manual performance were examined
      using a sham-controlled cross-over design in a sample of older and younger
      participants. The atDCS effect on resting-state inhibition differed in direction,
      magnitude, and timing, i.e., late relative release of inhibition in the younger
      and early relative increase in inhibition in the older. More pronounced release
      of event-related inhibition after atDCS was exclusively seen in the older. Event
      related modulation of inhibition prior to stimulation predicted the magnitude of
      atDCS-induced effects on resting-state inhibition. Specifically, older
      participants with high modulatory capacity showed a disinhibitory effect
      comparable to the younger. Beneficial effects on behavior were mainly seen in the
      older and in tasks requiring higher dexterity, no clear association with
      physiological changes was found. Differential effects of atDCS on SICI, discussed
      to reflect GABAergic inhibition at the level of the primary motor cortex, might
      be distinct in older and younger participants depending on the functional
      integrity of the underlying neural network. Older participants with preserved
      modulatory capacity, i.e., a physiologically "young" motor network, were more
      likely to show a disinhibitory effect of atDCS. These results favor individually
      tailored application of tDCS with respect to specific target groups. 

PMID- 25071556
TI  - Intraindividual variability across cognitive tasks as a potential marker for
      prodromal Alzheimer's disease.
AB  - Recent studies have shown that increased cognitive intraindividual variability
      (IIV) across accuracy scores from tests representing different cognitive domains
      (across-domain IIV) might indicate prodromal Alzheimer's disease (AD). Although
      IIV has been proposed to index cognitive control processes, IIV across accuracy
      scores from cognitive control tasks (within-domain IIV) has not been examined in
      healthy controls subjects (HCS), mild cognitive impairment (MCI), and AD patients
      in a single comparative study. This study examines the discriminative properties
      of within-domain IIV, and across-domain IIV in 149 HCS, 31 MCI, and 26 AD. Three
      tasks representing different cognitive domains were identified to calculate
      across-domain IIV. Three other tasks representing cognitive control were
      identified to calculate within-domain IIV. The intraindividual standard deviation
      was calculated across accuracy scores. To compare IIV between groups, ANCOVAs
      with the covariates age, gender, education, and mean performance were computed.
      IIV scores in general were higher in AD vs. HCS (p < 0.01). Only across-domain
      IIV was higher in AD vs. MCI (p = 0.001), and only within-domain IIV was higher
      in MCI vs. HCS (p = 0.05). Within-domain IIV may constitute a cognitive marker
      for the detection of prodromal AD at the MCI stage, whereas across-domain IIV may
      detect beginning AD at the MCI stage. 

PMID- 25071559
TI  - Linking brain stroke risk factors to human movement features for the development
      of preventive tools.
AB  - This paper uses human movement analyses to assess the susceptibility of brain
      stroke, one of the most important causes of disability in elders. To that end, a
      computerized battery of nine neuromuscular tests has been designed and evaluated
      with a sample of 120 subjects with or without stoke risk factors. The kinematics
      of the movements produced was analyzed using a computational neuromuscular model
      and predictive characteristics were extracted. Logistic regression and linear
      discriminant analysis with leave-one-out cross-validation was used to infer the
      probability of presence of brain stroke risk factors. The clinical potential
      value of movement information for stroke prevention was assessed by computing
      area under the receiver operating characteristic curve (AUC) for the diagnostic
      of risk factors based on motion analysis. AUC mostly varying between 0.6 and 0.9
      were obtained, depending on the neuromuscular test and the risk factor
      investigated (obesity, diabetes, hypertension, hypercholesterolemia, cigarette
      smoking, and cardiac disease). Our results support the feasibility of the
      proposed methodology and its potential application for the development of brain
      stroke prevention tools. Although further research is needed to improve this
      methodology and its outcome, results are promising and the proposed approach
      should be of great interest for many experimenters open to novel approaches in
      preventive medicine and in gerontology. It should also be valuable for engineers,
      psychologists, and researchers using human movements for the development of
      diagnostic and neuromuscular assessment tools. 

PMID- 25071560
TI  - Why AMD is a disease of ageing and not of development: mechanisms and insights.
AB  - Ageing disorders can be defined as the progressive and cumulative outcome of
      several defective cellular mechanisms as well as metabolic pathways, consequently
      resulting in degeneration. Environment plays an important role in its
      pathogenesis. In contrast, developmental disorders arise from inherited mutations
      and usually the role of environmental factors in development of disease is
      minimal. Age related macular degeneration (AMD) is one such retinal degenerative
      disorder which starts with the progression of age. Metabolism plays an important
      role in initiation of such diseases of ageing. Cholesterol metabolism and their
      oxidized products like 7-ketocholesterol have been shown to adversely impact
      retinal pigment epithelium (RPE) cells. These molecules can initiate
      mitochondrial apoptotic processes and also influence the complements factors and
      expression of angiogenic proteins like VEGF etc. In this review we highlight why
      and how AMD is an ageing disorder and not a developmental disease substantiated
      by disrupted cholesterol metabolism common to several age related diseases. 

PMID- 25071558
TI  - Studying variability in human brain aging in a population-based German cohort
      rationale and design of 1000BRAINS.
AB  - The ongoing 1000 brains study (1000BRAINS) is an epidemiological and
      neuroscientific investigation of structural and functional variability in the
      human brain during aging. The two recruitment sources are the 10-year follow-up
      cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR
      MultiGeneration Study cohort, which comprises spouses and offspring of HNR
      subjects. The HNR is a longitudinal epidemiological investigation of
      cardiovascular risk factors, with a comprehensive collection of clinical,
      laboratory, socioeconomic, and environmental data from population-based subjects
      aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in
      2000, 2006, and 2011, and completed annual postal questionnaires on health
      status. 1000BRAINS accesses these HNR data and applies a separate protocol
      comprising: neuropsychological tests of attention, memory, executive functions
      and language; examination of motor skills; ratings of personality, life quality,
      mood and daily activities; analysis of laboratory and genetic data; and state-of
      the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter
      includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin
      mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor
      imaging, high-angular resolution diffusion imaging for detailed fiber tracking
      and for diffusion kurtosis imaging; (iii) resting-state and task-based functional
      MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the
      detection of vascular lesions and the mapping of white matter lesions. The unique
      design of 1000BRAINS allows: (i) comprehensive investigation of various
      influences including genetics, environment and health status on variability in
      brain structure and function during aging; and (ii) identification of the impact
      of selected influencing factors on specific cognitive subsystems and their
      anatomical correlates. 

PMID- 25071561
TI  - Age-related variations of visuo-motor adaptation beyond explicit knowledge.
AB  - Visuo-motor adaptation suffers at older working age. The age-related decline of
      behavioral adjustments is accompanied by reduced explicit knowledge of the visuo
      motor transformation. It disappears when explicit knowledge is kept constant
      across the age range, except for particularly high levels of explicit knowledge.
      According to these findings, at older adult age both the acquisition of explicit
      knowledge and its application for strategic corrections become poorer. Recently
      it has been posited that visuo-motor adaptation can involve model-free
      reinforcement mechanisms of learning in addition to model-based mechanisms. We
      tested whether age-related declines of reinforcement learning can also contribute
      to the age-related changes of visuo-motor adaptation. Therefore we enhanced the
      contribution of reinforcement learning to visuo-motor adaptation by way of
      introducing salient markers of success and failure during practice. With such
      modified practice conditions, there were residual age-related variations of
      behavioral adjustments at all levels of explicit knowledge, even when explicit
      knowledge was absent. The residual age-related variations were observed for
      practiced target directions only, but not for new target directions. These
      findings are consistent with an age-related decline of model-free reinforcement
      learning as a third factor in the age-related decline of visuo-motor adaptation.
      Under practice conditions, which spur model-free reward-based learning, this
      factor adds to the decrements of the acquisition of explicit knowledge and its
      use for strategic corrections. 

PMID- 25071562
TI  - Cortisol, cytokines, and hippocampal volume interactions in the elderly.
AB  - Separate bodies of literature report that elevated pro-inflammatory cytokines and
      cortisol negatively affect hippocampal structure and cognitive functioning,
      particularly in older adults. Although interactions between cytokines and
      cortisol occur through a variety of known mechanisms, few studies consider how
      their interactions affect brain structure. In this preliminary study, we assess
      the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL
      10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight
      community-dwelling older adults underwent blood draws for quantification of
      circulating cytokines and saliva collections to quantify the cortisol awakening
      response. Hippocampal volume measurements were made using structural magnetic
      resonance imaging. Elevated levels of waking cortisol in conjunction with higher
      concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal
      volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF
      alpha were also associated with smaller hippocampal volumes. These data provide
      preliminary evidence that higher cortisol, in conjunction with higher IL-6 and
      TNF-alpha, are associated with smaller hippocampal volume in older adults. We
      suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis
      and inflammation processes may explain hippocampal volume reductions in older
      adults better than either set of measures do in isolation. 

PMID- 25071557
TI  - A systematic review of type 2 diabetes mellitus and hypertension in imaging
      studies of cognitive aging: time to establish new norms.
AB  - The rising prevalence of type 2 diabetes (T2DM) and hypertension in older adults,
      and the deleterious effect of these conditions on cerebrovascular and brain
      health, is creating a growing discrepancy between the "typical" cognitive aging
      trajectory and a "healthy" cognitive aging trajectory. These changing health
      demographics make T2DM and hypertension important topics of study in their own
      right, and warrant attention from the perspective of cognitive aging neuroimaging
      research. Specifically, interpretation of individual or group differences in
      blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) or
      positron emission tomography (PET H2O(15)) signals as reflective of differences
      in neural activation underlying a cognitive operation of interest requires
      assumptions of intact vascular health amongst the study participants. Without
      adequate screening, inclusion of individuals with T2DM or hypertension in
      "healthy" samples may introduce unwanted variability and bias to brain and/or
      cognitive measures, and increase potential for error. We conducted a systematic
      review of the cognitive aging neuroimaging literature to document the extent to
      which researchers account for these conditions. Of the 232 studies selected for
      review, few explicitly excluded individuals with T2DM (9%) or hypertension (13%).
      A large portion had exclusion criteria that made it difficult to determine
      whether T2DM or hypertension were excluded (44 and 37%), and many did not mention
      any selection criteria related to T2DM or hypertension (34 and 22%). Of all the
      surveyed studies, only 29% acknowledged or addressed the potential influence of
      intersubject vascular variability on the measured BOLD or PET signals. To
      reinforce the notion that individuals with T2DM and hypertension should not be
      overlooked as a potential source of bias, we also provide an overview of
      metabolic and vascular changes associated with T2DM and hypertension, as they
      relate to cerebrovascular and brain health. 

PMID- 25071564
TI  - Laminin alpha2 Chain-Deficiency is Associated with microRNA Deregulation in
      Skeletal Muscle and Plasma.
AB  - microRNAs (miRNAs) are widespread regulators of gene expression, but little is
      known of their potential roles in congenital muscular dystrophy type 1A (MDC1A).
      MDC1A is a severe form of muscular dystrophy caused by mutations in the gene
      encoding laminin alpha2 chain. To gain insight into the pathophysiological roles
      of miRNAs associated with MDC1A pathology, laminin alpha2 chain-deficient mice
      were evaluated by quantitative PCR. We demonstrate that expression of muscle
      specific miR-1, miR-133a, and miR-206 is deregulated in laminin alpha2 chain
      deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with
      immune cell infiltration and fibrosis, respectively, is altered. Finally, we show
      that plasma levels of muscle-specific miRNAs are markedly elevated in laminin
      alpha2 chain-deficient mice and partially normalized in response to proteasome
      inhibition therapy. Altogether, our data suggest important roles for miRNAs in
      MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as
      promising biomarkers for the progression of MDC1A. 

PMID- 25071563
TI  - The potential applications of Apolipoprotein E in personalized medicine.
AB  - Personalized medicine uses various individual characteristics to guide medical
      decisions. Apolipoprotein (ApoE), the most studied polymorphism in humans, has
      been associated with several diseases. The purpose of this review is to elucidate
      the potential role of ApoE polymorphisms in personalized medicine, with a
      specific focus on neurodegenerative diseases, by giving an overview of its
      influence on disease risk assessment, diagnosis, prognosis, and therapy. This
      review is not a systematic inventory of the literature, but rather a summary and
      discussion of novel, influential and promising works in the field of ApoE
      research that could be valuable for personalized medicine. Empirical evidence
      suggests that ApoE genotype informs pre-symptomatic risk for a wide variety of
      diseases, is valuable for the diagnosis of type III dysbetalipoproteinemia,
      increases risk of dementia in neurodegenerative diseases, and is associated with
      a poor prognosis following acute brain damage. ApoE status appears to influence
      the efficacy of certain drugs, outcome of clinical trials, and might also give
      insight into disease prevention. Assessing ApoE genotype might therefore help to
      guide medical decisions in clinical practice. 

PMID- 25071565
TI  - New molecular targets and lifestyle interventions to delay aging sarcopenia.

PMID- 25071566
TI  - Safety margins in older adults increase with improved control of a dynamic
      object.
AB  - Older adults face decreasing motor capabilities due to pervasive neuromuscular
      degradations. As a consequence, errors in movement control increase. Thus, older
      individuals should maintain larger safety margins than younger adults. While this
      has been shown for object manipulation tasks, several reports on whole-body
      activities, such as posture and locomotion, demonstrate age-related reductions in
      safety margins. This is despite increased costs for control errors, such as a
      fall. We posit that this paradox could be explained by the dynamic challenge
      presented by the body or also an external object, and that age-related reductions
      in safety margins are in part due to a decreased ability to control dynamics. To
      test this conjecture we used a virtual ball-in-cup task that had challenging
      dynamics, yet afforded an explicit rendering of the physics and safety margin.
      The hypotheses were: (1) When manipulating an object with challenging dynamics,
      older adults have smaller safety margins than younger adults. (2) Older adults
      increase their safety margins with practice. Nine young and 10 healthy older
      adults practiced moving the virtual ball-in-cup to a target location in exactly 2
      s. The accuracy and precision of the timing error quantified skill, and the ball
      energy relative to an escape threshold quantified the safety margin. Compared to
      the young adults, older adults had increased timing errors, greater variability,
      and decreased safety margins. With practice, both young and older adults improved
      their ability to control the object with decreased timing errors and variability,
      and increased their safety margins. These results suggest that safety margins are
      related to the ability to control dynamics, and may explain why in tasks with
      simple dynamics older adults use adequate safety margins, but in more complex
      tasks, safety margins may be inadequate. Further, the results indicate that task
      specific training may improve safety margins in older adults. 

PMID- 25071567
TI  - Interactive effects of vascular risk burden and advanced age on cerebral blood
      flow.
AB  - Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to
      increased risk of cognitive impairment and Alzheimer's disease (AD); however the
      possible moderating effects of age and vascular risk burden on CBF in late life
      remain understudied. We examined the relationships among elevated vascular risk
      burden, age, CBF, and cognition. Seventy-one non-demented older adults completed
      an arterial spin labeling MR scan, neuropsychological assessment, and medical
      history interview. Relationships among vascular risk burden, age, and CBF were
      examined in a priori regions of interest (ROIs) previously implicated in aging
      and AD. Interaction effects indicated that, among older adults with elevated
      vascular risk burden (i.e., multiple vascular risk factors), advancing age was
      significantly associated with reduced cortical CBF whereas there was no such
      relationship for those with low vascular risk burden (i.e., no or one vascular
      risk factor). This pattern was observed in cortical ROIs including medial
      temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal
      (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal
      (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices.
      Furthermore, among those with elevated vascular risk, reduced CBF was associated
      with poorer cognitive performance. Such findings suggest that older adults with
      elevated vascular risk burden may be particularly vulnerable to cognitive change
      as a function of CBF reductions. Findings support the use of CBF as a potential
      biomarker in preclinical AD and suggest that vascular risk burden and regionally
      specific CBF changes may contribute to differential age-related cognitive
      declines. 

PMID- 25071568
TI  - A neurodegenerative vascular burden index and the impact on cognition.
AB  - A wide range of vascular burden factors has been identified to impact vascular
      function and structure as indicated by carotid intima-media thickness (IMT). On
      the basis of their impact on IMT, vascular factors may be selected and clustered
      in a vascular burden index (VBI). Since many vascular factors increase the risk
      of Alzheimer's disease (AD), a multifactorial neurodegenerative VBI may be
      related to early pathological processes in AD and cognitive decline in its
      preclinical stages. We investigated an elderly cohort at risk for
      neurodegeneration (TREND study, n = 1102) for the multifactorial influence of
      vascular burden factors on IMT measured by ultrasound. To create a VBI for this
      cohort, vascular factors and their definitions (considering medical history,
      medication, and/or blood marker data) were selected based on their statistical
      effects on IMT in multiple regressions including age and sex. The impact of the
      VBI on cognitive performance was assessed using the Trail-Making Test (TMT) and
      the consortium to establish a registry for Alzheimer's disease (CERAD)
      neuropsychological battery. IMT was significantly predicted by age (standardized
      beta = 0.26), sex (0.09; males > females) and the factors included in the VBI:
      obesity (0.18), hypertension (0.14), smoking (0.08), diabetes (0.07), and
      atherosclerosis (0.05), whereas other cardiovascular diseases or
      hypercholesterolemia were not significant. Individuals with 2 or more VBI factors
      compared to individuals without had an odds ratio of 3.17 regarding overly
      increased IMT ( >= 1.0 mm). The VBI showed an impact on executive control
      [log(TMT B-A), p = 0.047] and a trend toward decreased global cognitive function
      (CERAD total score, p = 0.057) independent of age, sex, and education. A VBI
      established on the basis of IMT may help to identify individuals with overly
      increased vascular burden linked to decreased cognitive function indicating
      neurodegenerative processes. The longitudinal study of this risk cohort will
      reveal the value of the VBI as prodromal marker for cognitive decline and AD. 

PMID- 25071569
TI  - Declined contrast sensitivity of neurons along the visual pathway in aging cats.
AB  - Changes in the visual cortex appear to mediate much of the visual degradation
      during normal aging. However, how aging affects different stages along the visual
      pathway is unclear. In the current study, the contrast response function, one of
      the most important properties of neurons from early visual areas to high brain
      areas, was systematically compared along the visual pathway, including the
      lateral geniculate nucleus (LGN), early visual cortices (A17 and A18), and
      posteromedial lateral suprasylvian cortex (PMLS, analog to the medial temporal
      area (MT) in monkeys) of young and old cats. We found that the effects of aging
      on the LGN were negligible, whereas those in the striate cortex were substantial,
      with even more severe degradation in the PMLS. Reduced contrast sensitivity of
      neurons in the three cortical areas was accompanied by enhanced maximal visual
      response, increased spontaneous activity, and decreased signal-to-noise ratio,
      while LGN neurons exhibited largely normal response properties. Our results
      suggested that there was a progressively greater effect of aging on neurons at
      successively higher stages in the visual pathway. 

PMID- 25071570
TI  - Quantitative ultrasound: measurement considerations for the assessment of
      muscular dystrophy and sarcopenia.

PMID- 25071571
TI  - The glial response to intracerebrally delivered therapies for neurodegenerative
      disorders: is this a critical issue?
AB  - The role of glial cells in the pathogenesis of many neurodegenerative conditions
      of the central nervous system (CNS) is now well established (as is discussed in
      other reviews in this special issue of Frontiers in Neuropharmacology). What is
      less clear is whether there are changes in these same cells in terms of their
      behavior and function in response to invasive experimental therapeutic
      interventions for these diseases. This has, and will continue to become more of
      an issue as we enter a new era of novel treatments which require the agent to be
      directly placed/infused into the CNS such as deep brain stimulation (DBS), cell
      transplants, gene therapies and growth factor infusions. To date, all of these
      treatments have produced variable outcomes and the reasons for this have been
      widely debated but the host astrocytic and/or microglial response induced by such
      invasively delivered agents has not been discussed in any detail. In this review,
      we have attempted to summarize the limited published data on this, in particular
      we discuss the small number of human post-mortem studies reported in this field.
      By so doing, we hope to provide a better description and understanding of the
      extent and nature of both the astrocytic and microglial response, which in turn
      could lead to modifications in the way these therapeutic interventions are
      delivered. 

PMID- 25071573
TI  - CaMKII comes of age in cardiac health and disease.

PMID- 25071572
TI  - Human pluripotent stem cells on artificial microenvironments: a high content
      perspective.
AB  - Self-renewing stem cell populations are increasingly considered as resources for
      cell therapy and tools for drug discovery. Human pluripotent stem (hPS) cells in
      particular offer a virtually unlimited reservoir of homogeneous cells and can be
      differentiated toward diverse lineages. Many diseases show impairment in self
      renewal or differentiation, abnormal lineage choice or other aberrant cell
      behavior in response to chemical or physical cues. To investigate these
      responses, there is a growing interest in the development of specific assays
      using hPS cells, artificial microenvironments and high content analysis. Several
      hurdles need to be overcome that can be grouped into three areas: (i)
      availability of robust, homogeneous, and consistent cell populations as a
      starting point; (ii) appropriate understanding and use of chemical and physical
      microenvironments; (iii) development of assays that dissect the complexity of
      cell populations in tissues while mirroring specific aspects of their behavior.
      Here we review recent progress in the culture of hPS cells and we detail the
      importance of the environment surrounding the cells with a focus on synthetic
      material and suitable high content analysis approaches. The technologies
      described, if properly combined, have the potential to create a paradigm shift in
      the way diseases are modeled and drug discovery is performed. 

PMID- 25071574
TI  - Iron overload in Plasmodium berghei-infected placenta as a pathogenesis mechanism
      of fetal death.
AB  - Plasmodium infection during gestation may lead to severe clinical manifestations
      including abortion, stillbirth, intrauterine growth retardation, and low birth
      weight. Mechanisms underlying such poor pregnancy outcomes are still unclear. In
      the animal model of severe placental malaria (PM), in utero fetal death
      frequently occurs and mothers often succumb to infection before or immediately
      after delivery. Plasmodium berghei-infected erythrocytes (IEs) continuously
      accumulate in the placenta, where they are then phagocytosed by fetal-derived
      placental cells, namely trophoblasts. Inside the phagosomes, disruption of IEs
      leads to the release of non-hemoglobin bound heme, which is subsequently
      catabolized by heme oxygenase-1 into carbon monoxide, biliverdin, and labile
      iron. Fine-tuned regulatory mechanisms operate to maintain iron homeostasis,
      preventing the deleterious effect of iron-induced oxidative stress. Our
      preliminary results demonstrate that iron overload in trophoblasts of P. berghei
      infected placenta is associated with fetal death. Placentas which supported
      normally developing embryos showed no iron accumulation within the trophoblasts.
      Placentas from dead fetuses showed massive iron accumulation, which was
      associated with parasitic burden. Here we present preliminary data suggesting
      that disruption of iron homeostasis in trophoblasts during the course of PM is a
      consequence of heme accumulation after intense IE engulfment. We propose that
      iron overload in placenta is a pathogenic component of PM, contributing to fetal
      death. The mechanism through which it operates still needs to be elucidated. 

PMID- 25071575
TI  - The role of iron in the skin and cutaneous wound healing.
AB  - In this review article we discuss current knowledge about iron in the skin and
      the cutaneous wound healing process. Iron plays a key role in both oxidative
      stress and photo-induced skin damage. The main causes of oxidative stress in the
      skin include reactive oxygen species (ROS) generated in the skin by ultraviolet
      (UVA) 320-400 nm portion of the UVA spectrum and biologically available iron. We
      also discuss the relationships between iron deficiency, anemia and cutaneous
      wound healing. Studies looking at this fall into two distinct groups. Early
      studies investigated the effect of anemia on wound healing using a variety of
      experimental methodology to establish anemia or iron deficiency and focused on
      wound-strength rather than effect on macroscopic healing or re-epithelialization.
      More recent animal studies have investigated novel treatments aimed at correcting
      the effects of systemic iron deficiency and localized iron overload. Iron
      overload is associated with local cutaneous iron deposition, which has numerous
      deleterious effects in chronic venous disease and hereditary hemochromatosis.
      Iron plays a key role in chronic ulceration and conditions such as rheumatoid
      arthritis (RA) and Lupus Erythematosus are associated with both anemia of chronic
      disease and dysregulation of local cutaneous iron hemostasis. Iron is a potential
      therapeutic target in the skin by application of topical iron chelators and novel
      pharmacological agents, and in delayed cutaneous wound healing by treatment of
      iron deficiency or underlying systemic inflammation. 

PMID- 25071576
TI  - Open label smoking cessation with varenicline is associated with decreased
      glutamate levels and functional changes in anterior cingulate cortex: preliminary
      findings.
AB  - RATIONALE: Varenicline, the most effective single agent for smoking cessation, is
      a partial agonist at alpha4beta2 nicotinic acetylcholine receptors. Increasing
      evidence implicates glutamate in the pathophysiology of addiction and one of the
      benefits of treatment for smoking cessation is the ability to regain cognitive
      control. OBJECTIVE: To evaluate the effects of 12-week varenicline administration
      on glutamate levels in the dorsal anterior cingulate cortex (dACC) and functional
      changes within the cognitive control network. METHODS: We used single-voxel
      proton magnetic resonance spectroscopy ((1)H-MRS) in the dACC and functional MRI
      (fMRI) during performance of a Stroop color-naming task before and after smoking
      cessation with varenicline in 11 healthy smokers (open label design). Using the
      dACC as a seed region, we evaluated functional connectivity changes using a
      psychophysiological interaction (PPI) analysis. RESULTS: We observed a
      significant decrease in dACC glutamate + glutamine (Glx)/Cr levels as well as
      significant blood oxygen level-dependent signal (BOLD) decreases in the rostral
      ACC/medial orbitofrontal cortex and precuneus/posterior cingulate cortex. These
      BOLD changes are suggestive of alterations in default mode network (DMN) function
      and are further supported by the results of the PPI analysis that revealed
      changes in connectivity between the dACC and regions of the DMN. Baseline
      measures of nicotine dependence and craving positively correlated with baseline
      Glx/Cr levels. CONCLUSIONS: These results suggest possible mechanisms of action
      for varenicline such as reduction in Glx levels in dACC and shifts in BOLD
      connectivity between large scale brain networks. They also suggest a role for ACC
      Glx in the modulation of behavior. Due to the preliminary nature of this study
      (lack of control group and small sample size), future studies are needed to
      replicate these findings.

PMID- 25071578
TI  - Relevance of G-quadruplex structures to pharmacogenetics.
AB  - G-quadruplexes are non-canonical secondary structures formed within nucleic acids
      that are involved in modulating cellular processes such as replication, gene
      regulation, recombination and epigenetics. Within genes, there is mounting
      evidence of G-quadruplex involvement in transcriptional and post transcriptional
      regulation. We report the presence of potential G-quadruplex motifs within
      relevant sites of some important pharmacogenes and discuss the possible
      implications of this on the function and expression of these genes. Appreciating
      the location and potential functions of these motifs may be of value when
      considering the impacts of some pharmacogenetic variants. G-quadruplexes are also
      the focus of drug development efforts in oncology and we highlight the broader
      pharmacological implications of treatment strategies that may target G
      quadruplexes. 

PMID- 25071577
TI  - Nanodrug delivery in reversing multidrug resistance in cancer cells.
AB  - Different mechanisms in cancer cells become resistant to one or more
      chemotherapeutics is known as multidrug resistance (MDR) which hinders
      chemotherapy efficacy. Potential factors for MDR includes enhanced drug
      detoxification, decreased drug uptake, increased intracellular nucleophiles
      levels, enhanced repair of drug induced DNA damage, overexpression of drug
      transporter such as P-glycoprotein(P-gp), multidrug resistance-associated
      proteins (MRP1, MRP2), and breast cancer resistance protein (BCRP). Currently
      nanoassemblies such as polymeric/solid lipid/inorganic/metal nanoparticles,
      quantum dots, dendrimers, liposomes, micelles has emerged as an innovative,
      effective, and promising platforms for treatment of drug resistant cancer cells.
      Nanocarriers have potential to improve drug therapeutic index, ability for
      multifunctionality, divert ABC-transporter mediated drug efflux mechanism and
      selective targeting to tumor cells, cancer stem cells, tumor initiating cells, or
      cancer microenvironment. Selective nanocarrier targeting to tumor overcomes dose
      limiting side effects, lack of selectivity, tissue toxicity, limited drug access
      to tumor tissues, high drug doses, and emergence of multiple drug resistance with
      conventional or combination chemotherapy. Current review highlights various
      nanodrug delivery systems to overcome mechanism of MDR by neutralizing, evading,
      or exploiting the drug efflux pumps and those independent of drug efflux pump
      mechanism by silencing Bcl-2 and HIF1alpha gene expressions by siRNA and miRNA,
      modulating ceramide levels and targeting NF-kappaB. "Theragnostics" combining a
      cytotoxic agent, targeting moiety, chemosensitizing agent, and diagnostic imaging
      aid are highlighted as effective and innovative systems for tumor localization
      and overcoming MDR. Physical approaches such as combination of drug with
      thermal/ultrasound/photodynamic therapies to overcome MDR are focused. The review
      focuses on newer drug delivery systems developed to overcome MDR in cancer cell. 

PMID- 25071579
TI  - Recent methods for measuring dopamine D3 receptor occupancy in vivo: importance
      for drug development.
AB  - There is considerable interest in developing highly selective dopamine (DA) D3
      receptor ligands for a variety of mental health disorders. DA D3 receptors have
      been implicated in Parkinson's disease, schizophrenia, anxiety, depression, and
      substance use disorders. The most concrete evidence suggests a role for the D3
      receptor in drug-seeking behaviors. D3 receptors are a subtype of D2 receptors,
      and traditionally the functional role of these two receptors has been difficult
      to differentiate. Over the past 10-15 years a number of compounds selective for
      D3 over D2 receptors have been developed. However, translating these findings
      into clinical research has been difficult as many of these compounds cannot be
      used in humans. Therefore, the functional data involving the D3 receptor in drug
      addiction mostly comes from pre-clinical studies. Recently, with the advent of
      [(11)C]-(+)-PHNO, it has become possible to image D3 receptors in the human brain
      with increased selectivity and sensitivity. This is a significant innovation over
      traditional methods such as [(11)C]-raclopride that cannot differentiate between
      D2 and D3 receptors. The use of [(11)C]-(+)-PHNO will allow for further
      delineation of the role of D3 receptors. Here, we review recent evidence that the
      role of the D3 receptor has functional importance and is distinct from the role
      of the D2 receptor. We then introduce the utility of analyzing [(11)C]-(+)-PHNO
      binding by region of interest. This novel methodology can be used in pre-clinical
      and clinical approaches for the measurement of occupancy of both D3 and D2
      receptors. Evidence that [(11)C]-(+)-PHNO can provide insights into the function
      of D3 receptors in addiction is also presented. 

PMID- 25071580
TI  - Herbal medicines in Brazil: pharmacokinetic profile and potential herb-drug
      interactions.
AB  - A plethora of active compounds found in herbal medicines can serve as substrate
      for enzymes involved in the metabolism of xenobiotics. When a medicinal plant is
      co-administered with a conventional drug and little or no information is known
      about the pharmacokinetics of the plant metabolites, there is an increased risk
      of potential herb-drug interactions. Moreover, genetic polymorphisms in a
      population may act to predispose individuals to adverse reactions. The use of
      herbal medicines is rapidly increasing in many countries, particularly Brazil
      where the vast biodiversity is a potential source of new and more affordable
      treatments for numerous conditions. Accordingly, the Brazilian Unified Public
      Health System (SUS) produced a list of 71 plant species of interest, which could
      be made available to the population in the near future. Physicians at SUS
      prescribe a number of essential drugs and should herbal medicines be added to
      this system the chance of herb-drug interactions further increases. A review of
      the effects of these medicinal plants on Phase 1 and Phase 2 metabolic mechanisms
      and the transporter P-glycoprotein was conducted. The results have shown that
      approximately half of these medicinal plants lack any pharmacokinetic data.
      Moreover, most of the studies carried out are in vitro. Only a few reports on
      herb-drug interactions with essential drugs prescribed by SUS were found,
      suggesting that very little attention is being given to the safety of herbal
      medicines. Here we have taken this information to discuss the potential
      interactions between herbal medicines and essential drugs prescribed to Brazilian
      patients whilst taking into account the most common polymorphisms present in the
      Brazilian population. A number of theoretical interactions are pinpointed but
      more pharmacokinetic studies and pharmacovigilance data are needed to ascertain
      their clinical significance. 

PMID- 25071581
TI  - ABC transporters in CSCs membranes as a novel target for treating tumor relapse.
AB  - CSCs are responsible for the high rate of recurrence and chemoresistance of
      different types of cancer. The current antineoplastic agents able to inhibit bulk
      replicating cancer cells and radiation treatment are not efficacious toward CSCs
      since this subpopulation has several intrinsic mechanisms of resistance. Among
      these mechanisms, the expression of ATP-Binding Cassette (ABC) transporters
      family and the activation of different signaling pathways (such as Wnt/beta
      catenin signaling, Hedgehog, Notch, Akt/PKB) are reported. Therefore, considering
      ABC transporters expression on CSCs membranes, compounds able to modulate MDR
      could induce cytotoxicity in these cells disclosing an exciting and alternative
      strategy for targeting CSCs in tumor therapy. The next challenge in the cure of
      cancer relapse may be a multimodal strategy, an approach where specific CSCs
      targeting drugs exert simultaneously the ability to circumvent tumor drug
      resistance (ABC transporters modulation) and cytotoxic activity toward CSCs and
      the corresponding differentiated tumor cells. The efficacy of suggested
      multimodal strategy could be probed by using several scaffolds active toward MDR
      pumps on CSCs isolated by tumor specimens. 

PMID- 25071584
TI  - Role of [Ca(2+)]i and F-actin on mesothelial barrier function.
AB  - The mesothelial layer acts as a biological barrier between the organ and the
      enveloping serous cavity and may have functions of transport, equilibrium
      maintenance, and protection. However, the role of the mesothelial cells in
      regulation of pleural permeability remains essentially undefined. The present
      study was designed to clarify the effects of bradykinin, histamine, and thrombin
      on permeability in pleural mesothelial cells. Rat pleural mesothelial cells were
      cultured in vitro, and the permeability of mesothelial monolayers was evaluated
      by transmesothelial albumin diffusion and electrical resistance measurements.
      Furthermore, the temporal relationship between changes in the levels of [Ca(2+)]i
      and the mesothelial permeability was examined. Bradykinin (10 MUM), histamine (1
      mM), and thrombin (10 U) caused albumin diffusion within 5 min. The electrical
      resistance of mesothelial monolayer began falling within 5 min of adding each
      agent. Time and concentration dependency of changes in electrical resistance were
      almost the same as that in albumin diffusion. Each agent also induced a biphasic
      elevation of [Ca(2+)]i in pleural mesothelial cells. The concentration-dependency
      of the [Ca(2+)]i responses were almost similar to that noted for each agent
      induced albumin diffusion and electrical resistance fall. The increase in
      permeability occurred with reorganization of F-actin cytoskeleton and increased
      actin polymerization. These results suggest that the Ca(2+)- dependency of
      increases induced by these agents in mesothelial permeability have been related
      to the regulatory role of Ca(2+) in the F-actin cytoskeletal reorganization in
      pleural mesothelial cells. 

PMID- 25071583
TI  - Targeting pleiotropic signaling pathways to control adult cardiac stem cell fate
      and function.
AB  - The identification of different pools of cardiac progenitor cells resident in the
      adult mammalian heart opened a new era in heart regeneration as a means to
      restore the loss of functional cardiac tissue and overcome the limited
      availability of donor organs. Indeed, resident stem cells are believed to
      participate to tissue homeostasis and renewal in healthy and damaged myocardium
      although their actual contribution to these processes remain unclear. The poor
      outcome in terms of cardiac regeneration following tissue damage point out at the
      need for a deeper understanding of the molecular mechanisms controlling CPC
      behavior and fate determination before new therapeutic strategies can be
      developed. The regulation of cardiac resident stem cell fate and function is
      likely to result from the interplay between pleiotropic signaling pathways as
      well as tissue- and cell-specific regulators. Such a modular interaction-which
      has already been described in the nucleus of a number of different cells where
      transcriptional complexes form to activate specific gene programs-would account
      for the unique responses of cardiac progenitors to general and tissue-specific
      stimuli. The study of the molecular determinants involved in cardiac
      stem/progenitor cell regulatory mechanisms may shed light on the processes of
      cardiac homeostasis in health and disease and thus provide clues on the actual
      feasibility of cardiac cell therapy through tissue-specific progenitors. 

PMID- 25071585
TI  - Neurohumoral mechanisms associated with orthostasis: reaffirmation of the
      significant contribution of the heart rate response.
AB  - The inability to compensate for acute central hypovolemia underlies the clinical
      development of orthostatic hypotension and instability (e.g., syncope). Although
      neuro-humoral control of both cardiac output and peripheral vascular resistance
      contributes to hemodynamic stability during orthostasis, a notion has been
      proposed that the failure of adequate peripheral vascular constriction rather
      than cardiac responses represents the primary mechanism underlying the
      development of orthostatic intolerance. This review article provides an
      opportunity to present compelling evidence captured over the past 30 years in our
      laboratory to support the concept that neural-mediated tachycardia during
      orthostasis in healthy individuals represents a critical response to tolerating
      acute reduction in central blood volume in addition to, and independent of,
      peripheral vascular constriction. In this review paper, data are presented from
      experiments using graded lower body negative pressure (LBNP) as a method to
      induce orthostatic intolerance in two experimental human models: (1) comparison
      of heart rate and autonomic responses in individuals with relatively high and low
      tolerance to LBNP; and (2) vagal and sympathetic blockade of cardiac neural
      control. These experiments revealed that: (1) greater elevations in heart rate
      are associated with higher orthostatic (LBNP) tolerance; (2) higher orthostatic
      heart rate is associated with greater sympathetic nerve activity and withdrawal
      of vagally-mediated cardiac baroreflex response; and (3) non-specific sympathetic
      blockade causes a pronounced reduction in heart rate and LBNP tolerance. Cardiac
      parasympathetic withdrawal contributes to protection against development of
      hypotension during the initial seconds of transition to an orthostatic challenge,
      while the primary mechanism by which tachycardia defends orthostatic stability in
      healthy subjects for extended durations is mediated predominantly through
      sympathetic adrenergic control. 

PMID- 25071586
TI  - Kallikrein-related peptidase-4 (KLK4): role in enamel formation and revelations
      from ablated mice.
AB  - Enamel development occurs in stages. During the secretory stage, a soft protein
      rich enamel layer is produced that expands to reach its final thickness. During
      the maturation stage, proteins are removed and the enamel matures into the
      hardest substance in the body. KLK4 is expressed during the transition from
      secretory to the maturation stage and its expression continues throughout
      maturation. KLK4 is a glycosylated chymotrypsin-like serine protease that cleaves
      enamel matrix proteins prior to their export out of the hardening enamel layer.
      Mutations in KLK4 can cause autosomal recessive, non-syndromic enamel
      malformations in humans and mice. Klk4 ablated mice initially have normal-looking
      teeth with enamel of full thickness. However, the enamel is soft and protein
      rich. Three findings are notable from Klk4 ablated mice: first, enamel rods fall
      from the interrod enamel leaving behind empty holes where the enamel fractures
      near the underlying dentin surface. Second, the ~10,000 crystallites that
      normally fuse to form a solid enamel rod fail to grow together in the ablated
      mice and can fall out of the rods. Third, and most striking, the crystallites
      grow substantially in width and thickness (a- and b-axis) in the ablated mice
      until they almost interlock. The crystallites grow in defined enamel rods, but
      interlocking is prevented presumably because too much protein remains.
      Conventional thought holds that enamel proteins bind specifically to the sides of
      enamel crystals to inhibit growth in width and thickness so that the thin, ribbon
      like enamel crystallites grow predominantly in length. Results from Klk4 ablated
      mice demonstrate that this convention requires updating. An alternative mechanism
      is proposed whereby enamel proteins serve to form a mold or support structure
      that shapes and orients the mineral ribbons as they grow in length. The remnants
      of this support structure must be removed by KLK4 so that the crystallites can
      interlock to form fully hardened enamel. 

PMID- 25071587
TI  - Resting sympathetic baroreflex sensitivity in subjects with low and high
      tolerance to central hypovolemia induced by lower body negative pressure.
AB  - Central hypovolemia elicited by orthostasis or hemorrhage triggers
      sympathetically-mediated baroreflex responses to maintain organ perfusion; these
      reflexes are less sensitive in patients with orthostatic intolerance, and during
      conditions of severe blood loss, may result in cardiovascular collapse
      (decompensatory or circulatory shock). The ability to tolerate central
      hypovolemia is variable and physiological factors contributing to tolerance are
      emerging. We tested the hypothesis that resting muscle sympathetic nerve activity
      (MSNA) and sympathetic baroreflex sensitivity (BRS) are attenuated in male and
      female subjects who have low tolerance (LT) to central hypovolemia induced by
      lower body negative pressure (LBNP). MSNA and diastolic arterial pressure (DAP)
      were recorded in 47 human subjects who subsequently underwent LBNP to tolerance
      (onset of presyncopal symptoms). LT subjects experienced presyncopal symptoms
      prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT)
      experienced presyncopal symptoms after completing LBNP of -60 mm Hg. Contrary to
      our hypothesis, resting MSNA burst incidence was not different between LT and HT
      subjects, and was not related to time to presyncope. BRS was assessed as the
      slope of the relationship between spontaneous fluctuations in DAP and MSNA during
      5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or
      equal to 0.5 in 37 subjects (LT: n = 9; HT: n = 28), and BRS was not different
      between LT and HT (-1.8 +/- 0.3 vs. -2.2 +/- 0.2 bursts.(100 beats)(-1) .mm Hg(
      1), p = 0.29). We conclude that tolerance to central hypovolemia is not related
      to either resting MSNA or sympathetic BRS. 

PMID- 25071582
TI  - HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease.
AB  - Iron accumulation and associated oxidative stress in the brain have been
      consistently found in several neurodegenerative diseases. Multiple genetic
      studies have been undertaken to try to identify a cause of neurodegenerative
      diseases but direct connections have been rare. In the iron field, variants in
      the HFE gene that give rise to a protein involved in cellular iron regulation,
      are associated with iron accumulation in multiple organs including the brain.
      There is also substantial epidemiological, genetic, and molecular evidence of
      disruption of cholesterol homeostasis in several neurodegenerative diseases, in
      particular Alzheimer's disease (AD). Despite the efforts that have been made to
      identify factors that can trigger the pathological events associated with
      neurodegenerative diseases they remain mostly unknown. Because molecular
      phenotypes such as oxidative stress, synaptic failure, neuronal loss, and
      cognitive decline, characteristics associated with AD, have been shown to result
      from disruption of a number of pathways, one can easily argue that the phenotype
      seen may not arise from a linear sequence of events. Therefore, a multi-targeted
      approach is needed to understand a complex disorder like AD. This can be achieved
      only when knowledge about interactions between the different pathways and the
      potential influence of environmental factors on them becomes available. Toward
      this end, this review discusses what is known about the roles and interactions of
      iron and cholesterol in neurodegenerative diseases. It highlights the effects of
      gene variants of HFE (H63D- and C282Y-HFE) on iron and cholesterol metabolism and
      how they may contribute to understanding the etiology of complex
      neurodegenerative diseases. 

PMID- 25071588
TI  - Emerging trend in second messenger communication and myoendothelial feedback.
AB  - Over the past decade, second messenger communication has emerged as one of the
      intriguing topics in the field of vasomotor control. Of particular interest has
      been the idea of second messenger flux from smooth muscle to endothelium
      initiating a feedback response that attenuates constriction. Mechanistic details
      of the precise signaling cascade have until recently remained elusive. In this
      perspective, we introduce readers to how myoendothelial gap junctions could
      enable sufficient inositol trisphosphate flux to initiate endothelial Ca(2+)
      events that activate Ca(2+) sensitive K(+) channels. The resulting
      hyperpolarizing current would in turn spread back through the same myoendothelial
      gap junctions to moderate smooth muscle depolarization and constriction. In
      discussing this defined feedback mechanism, this brief manuscript will stress the
      importance of microdomains and of discrete cellular signaling. 

PMID- 25071590
TI  - The antioxidants dilemma: are they potentially immunosuppressants and
      carcinogens?

PMID- 25071592
TI  - Could whole-body cryotherapy (below -100 degrees C) improve muscle recovery from
      muscle damage?

PMID- 25071591
TI  - Adrenal adrenoceptors in heart failure.
AB  - Heart failure (HF) is a chronic clinical syndrome characterized by the reduction
      in left ventricular (LV) function and it represents one of the most important
      causes of morbidity and mortality worldwide. Despite considerable advances in
      pharmacological treatment, HF represents a severe clinical and social burden.
      Sympathetic outflow, characterized by increased circulating catecholamines (CA)
      biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as
      beta-blockers) are presently being used for the treatment of this disease.
      Adrenal gland secretes Epinephrine (80%) and Norepinephrine (20%) in response to
      acetylcholine stimulation of nicotinic cholinergic receptors on the chromaffin
      cell membranes. This process is regulated by adrenergic receptors (ARs):
      alpha2ARs inhibit CA release through coupling to inhibitory Gi-proteins, and beta
      ARs (mainly beta2ARs) stimulate CA release through coupling to stimulatory Gs
      proteins. All ARs are G-protein-coupled receptors (GPCRs) and GPCR kinases (GRKs)
      regulate their signaling and function. Adrenal GRK2-mediated alpha2AR
      desensitization and downregulation are increased in HF and seem to be a
      fundamental regulator of CA secretion from the adrenal gland. Consequently,
      restoration of adrenal alpha2AR signaling through the inhibition of GRK2 is a
      fascinating sympatholytic therapeutic strategy for chronic HF. This strategy
      could have several significant advantages over existing HF pharmacotherapies
      minimizing side-effects on extra-cardiac tissues and reducing the chronic
      activation of the renin-angiotensin-aldosterone and endothelin systems. The role
      of adrenal ARs in regulation of sympathetic hyperactivity opens interesting
      perspectives in understanding HF pathophysiology and in the identification of new
      therapeutic targets. 

PMID- 25071589
TI  - Vitamin D in inflammatory diseases.
AB  - Changes in vitamin D serum levels have been associated with inflammatory
      diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis,
      systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or
      asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling
      modulates many inflammatory responses on several levels. This includes (i) the
      regulation of the expression of genes which generate pro-inflammatory mediators,
      such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with
      transcription factors, such as NF-kappaB, which regulate the expression of
      inflammatory genes and (iii) the activation of signaling cascades, such as MAP
      kinases which mediate inflammatory responses. Vitamin D targets various tissues
      and cell types, a number of which belong to the immune system, such as
      monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading
      to individual responses of each cell type. One hallmark of these specific vitamin
      D effects is the cell-type specific regulation of genes involved in the
      regulation of inflammatory processes and the interplay between vitamin D
      signaling and other signaling cascades involved in inflammation. An important
      task in the near future will be the elucidation of the regulatory mechanisms that
      are involved in the regulation of inflammatory responses by vitamin D on the
      molecular level by the use of techniques such as chromatin immunoprecipitation
      (ChIP), ChIP-seq, and FAIRE-seq. 

PMID- 25071594
TI  - Advances in systems immunology and cancer.

PMID- 25071593
TI  - Vitamin D: a critical and essential micronutrient for human health.
AB  - Vitamin D is a micronutrient that is needed for optimal health throughout the
      whole life. Vitamin D3 (cholecalciferol) can be either synthesized in the human
      skin upon exposure to the UV light of the sun, or it is obtained from the diet.
      If the photoconversion in the skin due to reduced sun exposure (e.g., in
      wintertime) is insufficient, intake of adequate vitamin D from the diet is
      essential to health. Severe vitamin D deficiency can lead to a multitude of
      avoidable illnesses; among them are well-known bone diseases like osteoporosis, a
      number of autoimmune diseases, many different cancers, and some cardiovascular
      diseases like hypertension are being discussed. Vitamin D is found naturally in
      only very few foods. Foods containing vitamin D include some fatty fish, fish
      liver oils, and eggs from hens that have been fed vitamin D and some fortified
      foods in countries with respective regulations. Based on geographic location or
      food availability adequate vitamin D intake might not be sufficient on a global
      scale. The International Osteoporosis Foundation (IOF) has collected the 25
      hydroxy-vitamin D plasma levels in populations of different countries using
      published data and developed a global vitamin D map. This map illustrates the
      parts of the world, where vitamin D did not reach adequate 25-hydroxyvitamin D
      plasma levels: 6.7% of the papers report 25-hydroxyvitamin D plasma levels below
      25 nmol/L, which indicates vitamin D deficiency, 37.3% are below 50 nmol/Land
      only 11.9% found 25-hydroxyvitamin D plasma levels above 75 nmol/L target as
      suggested by vitamin D experts. The vitamin D map is adding further evidence to
      the vitamin D insufficiency pandemic debate, which is also an issue in the
      developed world. Besides malnutrition, a condition where the diet does not match
      to provide the adequate levels of nutrients including micronutrients for growth
      and maintenance, we obviously have a situation where enough nutrients were
      consumed, but lacked to reach sufficient vitamin D micronutrient levels. The
      latter situation is known as hidden hunger. The inadequate vitamin D status
      impacts on health care costs, which in turn could result in significant savings,
      if corrected. Since little is known about the effects on the molecular level that
      accompany the pandemic like epigenetic imprinting, the insufficiency-triggered
      gene regulations or the genetic background influence on the body to maintain
      metabolic resilience, future research will be needed. The nutrition community is
      highly interested in the molecular mechanism that underlies the vitamin D
      insufficiency caused effect. In recent years, novel large scale technologies have
      become available that allow the simultaneous acquisition of transcriptome,
      epigenome, proteome, or metabolome data in cells of organs. These important
      methods are now used for nutritional approaches summarized in emerging scientific
      fields of nutrigenomics, nutrigenetics, or nutriepigenetics. It is believed that
      with the help of these novel concepts further understanding can be generated to
      develop future sustainable nutrition solutions to safeguard nutrition security. 

PMID- 25071596
TI  - Self-measure of heart rate variability (HRV) and arrhythmia to monitor and to
      manage atrial arrhythmias: personal experience with high intensity interval
      exercise (HIIE) for the conversion to sinus rhythm.

PMID- 25071595
TI  - Disparities in the consequences of sarcopenia: implications for African American
      Veterans.

PMID- 25071598
TI  - Reduced vasodilator function following acute resistance exercise in obese women.
AB  - Obesity contributes to stress induced impairments in endothelium-dependent
      vasodilation (EDV), a precursor to atherosclerosis. Since obesity is associated
      with inflammation and oxidative stress, we sought to determine if a single bout
      of strenuous weight lifting (SWL) reduces EDV among sedentary obese adults.
      Participants included 9 obese (OB) (BMI 30.0-40.0 kg/m(2)) and 8 lean (LN) (BMI
      18.5-24.9 kg/m(2)) sedentary young women. All participants underwent a single
      bout of SWL using a progressive leg-press protocol. Brachial artery flow-mediated
      dilation (FMD) (an index of EDV) was determined using ultrasonography before and
      after SWL. Sublingual nitroglycerin (NTG) was used to determine brachial artery
      endothelium-independent vasodilation following SWL. Brachial artery FMD was
      significantly reduced in OB and LN women (LN: 6.4 +/- 1.6%, p = 0.22) after SWL.
      There was no difference in the magnitude of change pre- and post-SWL between
      groups (OB: -2.4 +/- 0.6% and LN: -2.2 +/- 1.6%, p = 0.84). Dilation to NTG was
      lower in OB (21.6 +/- 1.3%) compared to LN women (27.6 +/- 2.1%, p = 0.02) and
      associated with body weight (r = -0.70, p = 0.01). These data suggest that EDV is
      reduced in woman after acute resistance exercise. Dilations to NTG were lower in
      obese compared to lean woman and associated with body weight suggesting that
      changes in sensitivity of blood vessels to NO occurs during obesity. These
      findings may be important for understanding vascular risk following acute
      exercise in obesity. 

PMID- 25071599
TI  - The flexible structure of the K24S28 region of Leucine-Rich Amelogenin Protein
      (LRAP) bound to apatites as a function of surface type, calcium, mutation, and
      ionic strength.
AB  - Leucine-Rich Amelogenin Protein (LRAP) is a member of the amelogenin family of
      biomineralization proteins, proteins which play a critical role in enamel
      formation. Recent studies have revealed the structure and orientation of the N-
      and C-terminus of LRAP bound to hydroxyapatite (HAP), a surface used as an analog
      of enamel. The structure of one region, K24 to S28, was found to be sensitive to
      phosphorylation of S16, the only naturally observed site of serine
      phosphorylation in LRAP, suggesting that K24S28 may sit at a key region of
      structural flexibility and play a role in the protein's function. In this work,
      we investigated the sensitivity of the structure and orientation of this region
      when bound to HAP as a function of several factors which may vary during enamel
      formation to influence structure: the ionic strength (0.05, 0.15, 0.2 M), the
      calcium concentration (0.07 and 0.4 mM), and the surface to which it is binding
      [HAP and carbonated apatite (CAP), a more direct mimic of enamel]. A naturally
      occurring mutation found in amelogenin (T21I) was also investigated. The
      structure in the K24S28 region of the protein was found to be sensitive to these
      conditions, with the CAP surface and excess Ca(2+) (8:1 [Ca(2+)]:[LRAP
      K24S28(+P)]) resulting in a tighter helix, while low ionic strength relaxed the
      helical structure. Higher ionic strength and the point mutation did not result in
      any structural change in this region. The distance of the backbone of K24 from
      the surface was most sensitive to excess Ca(2+) and in the T21I-mutation.
      Collectively, these data suggest that phosphorylated LRAP is able to accommodate
      structural changes while maintaining its interaction with the surface, and
      provides further evidence of the structural sensitivity of the K24S28 region, a
      sensitivity that may contribute to function in biomineralization. 

PMID- 25071600
TI  - Skeletal muscle tissue engineering: best bet or black beast?

PMID- 25071597
TI  - Insect prophenoloxidase: the view beyond immunity.
AB  - Insect prophenoloxidase (PPO) is an important innate immunity protein due to its
      involvement in cellular and humoral defense. It belongs to a group of type-3
      copper-containing proteins that occurs in almost all organisms. Insect PPO has
      been studied for over a century, and the PPO activation cascade is becoming
      clearer. The insect PPO activation pathway incorporates several important
      proteins, including pattern-recognition receptors (PGRP, beta GRP, and C-type
      lectins), serine proteases, and serine protease inhibitors (serpins). Due to
      their complexity, PPO activation mechanisms vary among insect species. Activated
      phenoloxidase (PO) oxidizes phenolic molecules to produce melanin around invading
      pathogens and wounds. The crystal structure of Manduca sexta PPO shows that a
      conserved amino acid, phenylalanine (F), can block the active site pocket. During
      activation, this blocker must be dislodged or even cleaved at the N-terminal
      sequence to expose the active site pockets and allow substrates to enter. Thanks
      to the crystal structure of M. sexta PPO, some domains and specific amino acids
      that affect PPO activities have been identified. Further studies of the
      relationship between PPO structure and enzyme activities will provide an
      opportunity to examine other type-3 copper proteins, and trace when and why their
      various physiological functions evolved. Recent researches show that insect PPO
      has a relationship with neuron activity, longevity, feces melanization
      (phytophagous insects) and development, which suggests that it is time for us to
      look back on insect PPO beyond the view of immunity in this review. 

PMID- 25071601
TI  - Systems physiology of the baroreflex during orthostatic stress: from animals to
      humans.
AB  - The baroreflex is a key mechanism involved in the control of arterial pressure
      (AP) during orthostasis in humans. However, the baroreflex is a closed-loop
      feedback system, from baroreceptor pressure input to systemic AP, and therefore
      requires open-loop experiments to identify its system characteristics. The
      requirement limits our ability to identify baroreflex system characteristics in
      humans. Open-loop research in animals has revealed dynamic and static
      characteristics of the two baroreflex subsystems: the neural and peripheral arcs.
      The neural arc, from baroreceptor pressure input to sympathetic nerve activity
      (SNA), has high-pass dynamic characteristics, indicating that more rapid change
      in input AP causes greater response in SNA. In contrast, the peripheral arc, from
      SNA input to systemic AP, has low-pass characteristics. Orthostasis increases the
      gain of the neural arc, which compensates for the lower transfer gain of the
      peripheral arc and in turn maintains total baroreflex function. Here, I discuss
      the possibility that baroreflex subsystem characteristics identified in animals
      can be applicable to the human sympathetic response to orthostasis, with a focus
      on loading speed-dependence of orthostatic sympathetic activation. 

PMID- 25071602
TI  - Complex oscillatory redox dynamics with signaling potential at the edge between
      normal and pathological mitochondrial function.
AB  - The time-keeping properties bestowed by oscillatory behavior on functional
      rhythms represent an evolutionarily conserved trait in living systems.
      Mitochondrial networks function as timekeepers maximizing energetic output while
      tuning reactive oxygen species (ROS) within physiological levels compatible with
      signaling. In this work, we explore the potential for timekeeping functions
      dependent on mitochondrial dynamics with the validated two-compartment
      mitochondrial energetic-redox (ME-R) computational model, that takes into account
      (a) four main redox couples [NADH, NADPH, GSH, Trx(SH)2], (b) scavenging systems
      (glutathione, thioredoxin, SOD, catalase) distributed in matrix and extra-matrix
      compartments, and (c) transport of ROS species between them. Herein, we describe
      that the ME-R model can exhibit highly complex oscillatory dynamics in
      energetic/redox variables and ROS species, consisting of at least five
      frequencies with modulated amplitudes and period according to power spectral
      analysis. By stability analysis we describe that the extent of steady state-as
      against complex oscillatory behavior-was dependent upon the abundance of Mn and
      Cu, Zn SODs, and their interplay with ROS production in the respiratory chain.
      Large parametric regions corresponding to oscillatory dynamics of increasingly
      complex waveforms were obtained at low Cu, Zn SOD concentration as a function of
      Mn SOD. This oscillatory domain was greatly reduced at higher levels of Cu, Zn
      SOD. Interestingly, the realm of complex oscillations was located at the edge
      between normal and pathological mitochondrial energetic behavior, and was
      characterized by oxidative stress. We conclude that complex oscillatory dynamics
      could represent a frequency- and amplitude-modulated H2O2 signaling mechanism
      that arises under intense oxidative stress. By modulating SOD, cells could have
      evolved an adaptive compromise between relative constancy and the flexibility
      required under stressful redox/energetic conditions. 

PMID- 25071603
TI  - Control elements targeting Tgfb3 expression to the palatal epithelium are located
      intergenically and in introns of the upstream Ift43 gene.
AB  - Tgfb3 is strongly and specifically expressed in the epithelial tips of pre-fusion
      palatal shelves where it plays a critical non-redundant role in palatal fusion in
      both medial edge epithelial (MEE) cells and in a thin layer of flattened
      peridermal cells that covers the MEE. It is not known how Tgfb3 expression is
      regulated in these specific cell types. Using comparative genomics and transgenic
      reporter assays, we have identified cis-regulatory elements that could control
      Tgfb3 expression during palatogenesis. Our results show that a 61-kb genomic
      fragment encompassing the Tgfb3 gene drives remarkably specific reporter
      expression in the MEE and adjacent periderm. Within this fragment, we identified
      two small, non-coding, evolutionarily conserved regions in intron 2 of the
      neighboring Ift43 gene, and a larger region in the intervening sequence between
      the Ift43 and Tgfb3 genes, each of which could target reporter activity to the
      tips of pre-fusion/fusing palatal shelves. Identification of the cis-regulatory
      sequences controlling spatio-temporal Tgfb3 expression in palatal shelves is a
      key step toward understanding upstream regulation of Tgfb3 expression during
      palatogenesis and should enable the development of improved tools to investigate
      palatal epithelial fusion. 

PMID- 25071604
TI  - The regulation of angiogenesis by tissue cell-macrophage interactions.

PMID- 25071605
TI  - Convergence of vitamin D and lysophosphatidic acid signaling in stimulating human
      osteoblast maturation.

PMID- 25071606
TI  - The role of cannabinoid transmission in emotional memory formation: implications
      for addiction and schizophrenia.
AB  - Emerging evidence from both basic and clinical research demonstrates an important
      role for endocannabinoid (ECB) signaling in the processing of emotionally salient
      information, learning, and memory. Cannabinoid transmission within neural
      circuits involved in emotional processing has been shown to modulate the
      acquisition, recall, and extinction of emotionally salient memories and
      importantly, can strongly modulate the emotional salience of incoming sensory
      information. Two neural regions in particular, the medial prefrontal cortex (PFC)
      and the basolateral nucleus of the amygdala (BLA), play important roles in
      emotional regulation and contain high levels of cannabinoid receptors.
      Furthermore, both regions show profound abnormalities in neuropsychiatric
      disorders such as addiction and schizophrenia. Considerable evidence has
      demonstrated that cannabinoid transmission functionally interacts with dopamine
      (DA), a neurotransmitter system that is of exceptional importance for both
      addictive behaviors and the neuropsychopathology of disorders like schizophrenia.
      Research in our laboratory has focused on how cannabinoid transmission both
      within and extrinsic to the mesolimbic DA system, including the BLA -> mPFC
      circuitry, can modulate both rewarding and aversive emotional information. In
      this review, we will summarize clinical and basic neuroscience research
      demonstrating the importance of cannabinoid signaling within this neural
      circuitry. In particular, evidence will be reviewed emphasizing the importance of
      cannabinoid signaling within the BLA -> mPFC circuitry in the context of
      emotional salience processing, memory formation and memory-related plasticity. We
      propose that aberrant states of hyper or hypoactive ECB signaling within the
      amygdala-prefrontal cortical circuit may lead to dysregulation of
      mesocorticolimbic DA transmission controlling the processing of emotionally
      salient information. These disturbances may in turn lead to emotional processing,
      learning, and memory abnormalities related to various neuropsychiatric disorders,
      including addiction and schizophrenia-related psychoses. 

PMID- 25071608
TI  - Is inner speech the basis of auditory verbal hallucination in schizophrenia?

PMID- 25071609
TI  - Neuropsychopharmacology of psychosis: relation of brain signals, cognition, and
      chemistry.

PMID- 25071607
TI  - A methodological review of meditation research.
AB  - Despite over 50 years of research into the states of consciousness induced by
      various meditation practices, no clear neurophysiological signatures of these
      states have been found. Much of this failure can be attributed to the narrow
      range of variables examined in most meditation studies, with the focus being
      restricted to a search for correlations between neurophysiological measures and
      particular practices, without documenting the content and context of these
      practices. We contend that more meaningful results can be obtained by expanding
      the methodological paradigm to include multiple domains including: the cultural
      setting ("the place"), the life situation of the meditator ("the person"),
      details of the particular meditation practice ('the practice'), and the state of
      consciousness of the meditator ("the phenomenology"). Inclusion of variables from
      all these domains will improve the ability to predict the psychophysiological
      variables ("the psychophysiology") associated with specific meditation states and
      thus explore the mysteries of human consciousness. 

PMID- 25071610
TI  - On the relevance of mental imagery beyond stress-related psychiatric disorders.

PMID- 25071611
TI  - Brain reward and stress systems in addiction.

PMID- 25071613
TI  - Trail making test performance in youth varies as a function of anatomical
      coupling between the prefrontal cortex and distributed cortical regions.
AB  - While researchers have gained a richer understanding of the neural correlates of
      executive function in adulthood, much less is known about how these abilities are
      represented in the developing brain and what structural brain networks underlie
      them. Thus, the current study examined how individual differences in executive
      function, as measured by the Trail Making Test (TMT), relate to structural
      covariance in the pediatric brain. The sample included 146 unrelated, typically
      developing youth (80 females), ages 9-14 years, who completed a structural MRI
      scan of the brain and the Halstead-Reitan TMT (intermediate form). TMT scores
      used to index executive function included those that evaluated set-shifting
      ability: Trails B time (number-letter sequencing) and the difference in time
      between Trails B and A (number sequencing only). Anatomical coupling was measured
      by examining correlations between mean cortical thickness (MCT) across the entire
      cortical ribbon and individual vertex thickness measured at ~81,000 vertices. To
      examine how TMT scores related to anatomical coupling strength, linear regression
      was utilized and the interaction between age-normed TMT scores and both age and
      sex-normed MCT was used to predict vertex thickness. Results revealed that
      stronger Trails B scores were associated with greater anatomical coupling between
      a large swath of prefrontal cortex and the rest of cortex. For the difference
      between Trails B and A, a network of regions in the frontal, temporal, and
      parietal lobes was found to be more tightly coupled with the rest of cortex in
      stronger performers. This study is the first to highlight the importance of
      structural covariance in in the prediction of individual differences in executive
      function skills in youth. Thus, it adds to the growing literature on the neural
      correlates of childhood executive functions and identifies neuroanatomic coupling
      as a biological substrate that may contribute to executive function and
      dysfunction in childhood. 

PMID- 25071612
TI  - Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta
      Analysis.
AB  - BACKGROUND: Anxiety disorders increase risk of future cardiovascular disease
      (CVD) and mortality, even after controlling for confounds including smoking,
      lifestyle, and socioeconomic status, and irrespective of a history of medical
      disorders. While impaired vagal function, indicated by reductions in heart rate
      variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior
      studies have reported inconsistent findings highlighting the need for meta
      analysis. METHOD: Studies comparing resting-state HRV recordings in patients with
      an anxiety disorder as a primary diagnosis and healthy controls were considered
      for meta-analysis. RESULTS: Meta-analyses were based on 36 articles, including
      2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety
      disorders were characterized by lower HRV [high frequency (HF): Hedges' g = 
      0.29. 95% CI: -0.41 to -0.17, p < 0.001; time domain: Hedges' g = -0.45, 95% CI: 
      0.57 to -0.33, p < 0.001] than controls. Panic disorder (n = 447), post-traumatic
      stress disorder (n = 192), generalized anxiety disorder (n = 68), and social
      anxiety disorder (n = 90), but not obsessive-compulsive disorder (n = 40),
      displayed reductions in HF HRV relative to controls (all ps < 0.001). CONCLUSION:
      Anxiety disorders are associated with reduced HRV, findings associated with a
      small-to-moderate effect size. Findings have important implications for future
      physical health and well-being of patients, highlighting a need for comprehensive
      cardiovascular risk reduction.

PMID- 25071614
TI  - Psychocentricity and participant profiles: implications for lexical processing
      among multilinguals.
AB  - Lexical processing among bilinguals is often affected by complex patterns of
      individual experience. In this paper we discuss the psychocentric perspective on
      language representation and processing, which highlights the centrality of
      individual experience in psycholinguistic experimentation. We discuss
      applications to the investigation of lexical processing among multilinguals and
      explore the advantages of using high-density experiments with multilinguals. High
      density experiments are designed to co-index measures of lexical perception and
      production, as well as participant profiles. We discuss the challenges associated
      with the characterization of participant profiles and present a new data
      visualization technique, that we term Facial Profiles. This technique is based on
      Chernoff faces developed over 40 years ago. The Facial Profile technique seeks to
      overcome some of the challenges associated with the use of Chernoff faces, while
      maintaining the core insight that recoding multivariate data as facial features
      can engage the human face recognition system and thus enhance our ability to
      detect and interpret patterns within multivariate datasets. We demonstrate that
      Facial Profiles can code participant characteristics in lexical processing
      studies by recoding variables such as reading ability, speaking ability, and
      listening ability into iconically-related relative sizes of eye, mouth, and ear,
      respectively. The balance of ability in bilinguals can be captured by creating
      composite facial profiles or Janus Facial Profiles. We demonstrate the use of
      Facial Profiles and Janus Facial Profiles in the characterization of participant
      effects in the study of lexical perception and production. 

PMID- 25071615
TI  - Tracking the time course of multi-word noun phrase production with ERPs or on
      when (and why) cat is faster than the big cat.
AB  - Words are rarely produced in isolation. Yet, our understanding of multi-word
      production, and especially its time course, is still rather poor. In this
      research, we use event-related potentials to examine the production of multi-word
      noun phrases in the context of overt picture naming. We track the processing
      costs associated with the production of these noun phrases as compared with the
      production of bare nouns, from picture onset to articulation. Behavioral results
      revealed longer naming latencies for French noun phrases with determiners and pre
      nominal adjectives (D-A-N, the big cat) than for noun phrases with a determiner
      (D-N, the cat), or bare nouns (N, cat). The spatio-temporal analysis of the ERPs
      revealed differences in the duration of stable global electrophysiological
      patterns as a function of utterance format in two time windows, from ~190 to 300
      ms after picture onset, and from ~530 ms after picture onset to 100 ms before
      articulation. These findings can be accommodated in the following model. During
      grammatical encoding (here from ~190 to 300 ms), the noun and adjective lemmas
      are accessed in parallel, followed by the selection of the gender-agreeing
      determiner. Phonological encoding (after ~530 ms) operates sequentially. As a
      consequence, the phonological encoding process is longer for longer utterances.
      In addition, when determiners are repeated across trials, their phonological
      encoding can be anticipated or primed, resulting in a shortened encoding process.

PMID- 25071616
TI  - Multi-leveled objects: color as a case study.
AB  - The paper presents color as a case study for the analysis of phenomena that
      pertain to several levels of reality and are typically framed by different
      sciences and disciplines. Color, in fact, is studied by physics, biology,
      phenomenology, and esthetics, among others. Our thesis is that color is a
      different entity for each level of reality, and that for this reason color
      generates different observables in the epistemologies of the different sciences.
      By analyzing color as a paradigmatic case of an entity naturally spreading over
      different levels of reality, the paper raises the question as to whether making
      explicit the usually implicit ontological assumptions embedded within the
      different observables exploited by the different sciences may eventually clarify
      some of the difficulties of developing a comprehensive theory of color. 

PMID- 25071617
TI  - Less-structured time in children's daily lives predicts self-directed executive
      functioning.
AB  - Executive functions (EFs) in childhood predict important life outcomes. Thus,
      there is great interest in attempts to improve EFs early in life. Many
      interventions are led by trained adults, including structured training activities
      in the lab, and less-structured activities implemented in schools. Such programs
      have yielded gains in children's externally-driven executive functioning, where
      they are instructed on what goal-directed actions to carry out and when. However,
      it is less clear how children's experiences relate to their development of self
      directed executive functioning, where they must determine on their own what goal
      directed actions to carry out and when. We hypothesized that time spent in less
      structured activities would give children opportunities to practice self-directed
      executive functioning, and lead to benefits. To investigate this possibility, we
      collected information from parents about their 6-7 year-old children's daily,
      annual, and typical schedules. We categorized children's activities as
      "structured" or "less-structured" based on categorization schemes from prior
      studies on child leisure time use. We assessed children's self-directed executive
      functioning using a well-established verbal fluency task, in which children
      generate members of a category and can decide on their own when to switch from
      one subcategory to another. The more time that children spent in less-structured
      activities, the better their self-directed executive functioning. The opposite
      was true of structured activities, which predicted poorer self-directed executive
      functioning. These relationships were robust (holding across increasingly strict
      classifications of structured and less-structured time) and specific (time use
      did not predict externally-driven executive functioning). We discuss
      implications, caveats, and ways in which potential interpretations can be
      distinguished in future work, to advance an understanding of this fundamental
      aspect of growing up. 

PMID- 25071618
TI  - The relationship between postnatal depression, sociodemographic factors, levels
      of partner support, and levels of physical activity.
AB  - BACKGROUND: postnatal depression (PND) is defined as a psychological mood
      disorder that occurs in a mother within 6 weeks of her giving birth. It refers to
      an episode that causes mood disturbance and it could begin in, or extend into,
      the postpartum period. It is thought to have a high impact upon the mother's
      health as well as the family's functioning and the child's development. Socio
      demographic, psych-social, and physical activity factors may all contribute to
      postpartum mood and ability to cope with responsibilities. The primary aim of
      this study was to determine which of these factors predicted PND in postpartum
      women. A secondary aim was to identify the socio-demographic and psycho-social
      predictors of physical activity in postpartum women. METHODS: The study used a
      cross-sectional correlational design. A sample of 150 postpartum women was sent a
      package of six standardized questionnaires. RESULTS: There was no association
      between physical activity and PND; however, older mothers, mothers of younger
      children, mothers who are less reluctant to ask for help, and mothers who are
      more satisfied with the help they get experience lower levels of PND. Mothers of
      older babies, mothers with more children, and less educated mothers are more
      likely to engage in caregiving activities, whereas mothers with fewer children
      and higher levels of partner support are more likely to engage in occupational
      activities. None of the socio-demographic factors or any of the parenting factors
      predicted levels of sporting activity.

PMID- 25071620
TI  - Mindfulness-based interventions in schools-a systematic review and meta-analysis.
AB  - Mindfulness programs for schools are popular. We systematically reviewed the
      evidence regarding the effects of school-based mindfulness interventions on
      psychological outcomes, using a comprehensive search strategy designed to locate
      both published and unpublished studies. Systematic searches in 12 databases were
      performed in August 2012. Further studies were identified via hand search and
      contact with experts. Two reviewers independently extracted the data, also
      selecting information about intervention programs (elements, structure etc.),
      feasibility, and acceptance. Twenty-four studies were identified, of which 13
      were published. Nineteen studies used a controlled design. In total, 1348
      students were instructed in mindfulness, with 876 serving as controls, ranging
      from grade 1 to 12. Overall effect sizes were Hedge's g = 0.40 between groups and
      g = 0.41 within groups (p < 0.0001). Between group effect sizes for domains were:
      cognitive performance g = 0.80, stress g = 0.39, resilience g = 0.36, (all p <
      0.05), emotional problems g = 0.19 third person ratings g = 0.25 (both n.s.). All
      in all, mindfulness-based interventions in children and youths hold promise,
      particularly in relation to improving cognitive performance and resilience to
      stress. However, the diversity of study samples, variety in implementation and
      exercises, and wide range of instruments used require a careful and
      differentiated examination of data. There is great heterogeneity, many studies
      are underpowered, and measuring effects of Mindfulness in this setting is
      challenging. The field is nascent and recommendations will be provided as to how
      interventions and research of these interventions may proceed. 

PMID- 25071621
TI  - Moral judgment reloaded: a moral dilemma validation study.
AB  - We propose a revised set of moral dilemmas for studies on moral judgment. We
      selected a total of 46 moral dilemmas available in the literature and fine-tuned
      them in terms of four conceptual factors (Personal Force, Benefit Recipient,
      Evitability, and Intention) and methodological aspects of the dilemma formulation
      (word count, expression style, question formats) that have been shown to
      influence moral judgment. Second, we obtained normative codings of arousal and
      valence for each dilemma showing that emotional arousal in response to moral
      dilemmas depends crucially on the factors Personal Force, Benefit Recipient, and
      Intentionality. Third, we validated the dilemma set confirming that people's
      moral judgment is sensitive to all four conceptual factors, and to their
      interactions. Results are discussed in the context of this field of research,
      outlining also the relevance of our RT effects for the Dual Process account of
      moral judgment. Finally, we suggest tentative theoretical avenues for future
      testing, particularly stressing the importance of the factor Intentionality in
      moral judgment. Additionally, due to the importance of cross-cultural studies in
      the quest for universals in human moral cognition, we provide the new set
      dilemmas in six languages (English, French, German, Spanish, Catalan, and
      Danish). The norming values provided here refer to the Spanish dilemma set. 

PMID- 25071619
TI  - Predictors of early growth in academic achievement: the head-toes-knees-shoulders
      task.
AB  - Children's behavioral self-regulation and executive function (EF; including
      attentional or cognitive flexibility, working memory, and inhibitory control) are
      strong predictors of academic achievement. The present study examined the
      psychometric properties of a measure of behavioral self-regulation called the
      Head-Toes-Knees-Shoulders (HTKS) by assessing construct validity, including
      relations to EF measures, and predictive validity to academic achievement growth
      between prekindergarten and kindergarten. In the fall and spring of
      prekindergarten and kindergarten, 208 children (51% enrolled in Head Start) were
      assessed on the HTKS, measures of cognitive flexibility, working memory (WM), and
      inhibitory control, and measures of emergent literacy, mathematics, and
      vocabulary. For construct validity, the HTKS was significantly related to
      cognitive flexibility, working memory, and inhibitory control in prekindergarten
      and kindergarten. For predictive validity in prekindergarten, a random effects
      model indicated that the HTKS significantly predicted growth in mathematics,
      whereas a cognitive flexibility task significantly predicted growth in
      mathematics and vocabulary. In kindergarten, the HTKS was the only measure to
      significantly predict growth in all academic outcomes. An alternative
      conservative analytical approach, a fixed effects analysis (FEA) model, also
      indicated that growth in both the HTKS and measures of EF significantly predicted
      growth in mathematics over four time points between prekindergarten and
      kindergarten. Results demonstrate that the HTKS involves cognitive flexibility,
      working memory, and inhibitory control, and is substantively implicated in early
      achievement, with the strongest relations found for growth in achievement during
      kindergarten and associations with emergent mathematics. 

PMID- 25071622
TI  - Perceptions of document relevance.
AB  - This article presents a study of how humans perceive and judge the relevance of
      documents. Humans are adept at making reasonably robust and quick decisions about
      what information is relevant to them, despite the ever increasing complexity and
      volume of their surrounding information environment. The literature on document
      relevance has identified various dimensions of relevance (e.g., topicality,
      novelty, etc.), however little is understood about how these dimensions may
      interact. We performed a crowdsourced study of how human subjects judge two
      relevance dimensions in relation to document snippets retrieved from an internet
      search engine. The order of the judgment was controlled. For those judgments
      exhibiting an order effect, a q-test was performed to determine whether the order
      effects can be explained by a quantum decision model based on incompatible
      decision perspectives. Some evidence of incompatibility was found which suggests
      incompatible decision perspectives is appropriate for explaining interacting
      dimensions of relevance in such instances. 

PMID- 25071623
TI  - Emotion categorization of body expressions in narrative scenarios.
AB  - Humans can recognize emotions expressed through body motion with high accuracy
      even when the stimuli are impoverished. However, most of the research on body
      motion has relied on exaggerated displays of emotions. In this paper we present
      two experiments where we investigated whether emotional body expressions could be
      recognized when they were recorded during natural narration. Our actors were free
      to use their entire body, face, and voice to express emotions, but our resulting
      visual stimuli used only the upper body motion trajectories in the form of
      animated stick figures. Observers were asked to perform an emotion recognition
      task on short motion sequences using a large and balanced set of emotions
      (amusement, joy, pride, relief, surprise, anger, disgust, fear, sadness, shame,
      and neutral). Even with only upper body motion available, our results show
      recognition accuracy significantly above chance level and high consistency rates
      among observers. In our first experiment, that used more classic emotion
      induction setup, all emotions were well recognized. In the second study that
      employed narrations, four basic emotion categories (joy, anger, fear, and
      sadness), three non-basic emotion categories (amusement, pride, and shame) and
      the "neutral" category were recognized above chance. Interestingly, especially in
      the second experiment, observers showed a bias toward anger when recognizing the
      motion sequences for emotions. We discovered that similarities between motion
      sequences across the emotions along such properties as mean motion speed, number
      of peaks in the motion trajectory and mean motion span can explain a large
      percent of the variation in observers' responses. Overall, our results show that
      upper body motion is informative for emotion recognition in narrative scenarios. 

PMID- 25071624
TI  - Cognitive success: instrumental justifications of normative systems of reasoning.
AB  - In the first part of the paper (sec. 1-4), I argue that Elqayam and Evan's (2011)
      distinction between normative and instrumental conceptions of cognitive
      rationality corresponds to deontological vs. teleological accounts in meta
      ethics. I suggest that Elqayam and Evans' distinction be replaced by the
      distinction between a-priori intuition-based vs. a-posteriori success-based
      accounts of cognitive rationality. The value of cognitive success lies in its
      instrumental rationality for almost-all practical purposes. In the second part
      (sec. 5-7), I point out that the Elqayam and Evans's distinction between
      normative and instrumental rationality is coupled with a second distinction:
      between logically general vs. locally adaptive accounts of rationality. I argue
      that these are two independent distinctions that should be treated as independent
      dimensions. I also demonstrate that logically general systems of reasoning can be
      instrumentally justified. However, such systems can only be cognitively
      successful if they are paired with successful inductive reasoning, which is the
      area where the program of adaptive (ecological) rationality emerged, because
      there are no generally optimal inductive reasoning methods. I argue that the
      practical necessity of reasoning under changing environments constitutes a
      dilemma for ecological rationality, which I attempt to solve within a dual
      account of rationality. 

PMID- 25071625
TI  - What are the essential cognitive requirements for prospection (thinking about the
      future)?
AB  - Placing the future center stage as a way of understanding cognition is gaining
      attention in psychology. The general modern label for this is "prospection" which
      refers to the process of representing and thinking about possible future states
      of the world. Several theorists have claimed that episodic and prospective
      memory, as well as hypothetical thinking (mental simulation) and conditional
      reasoning are necessary cognitive faculties that enable prospection. Given the
      limitations in current empirical efforts connecting these faculties to
      prospection, the aim of this mini review is to argue that the findings show that
      they are sufficient, but not necessary for prospection. As a result, the short
      concluding section gives an outline of an alternative conceptualization of
      prospection. The proposal is that the critical characteristics of prospection are
      the discovery of, and maintenance of goals via causal learning. 

PMID- 25071626
TI  - Why studying intermodal duration discrimination matters.

PMID- 25071627
TI  - Commentary on "The role of domain-general cognitive control in language
      comprehension" by Fedorenko.

PMID- 25071629
TI  - A computational model of the temporal dynamics of plasticity in procedural
      learning: sensitivity to feedback timing.
AB  - The evidence is now good that different memory systems mediate the learning of
      different types of category structures. In particular, declarative memory
      dominates rule-based (RB) category learning and procedural memory dominates
      information-integration (II) category learning. For example, several studies have
      reported that feedback timing is critical for II category learning, but not for
      RB category learning-results that have broad support within the memory systems
      literature. Specifically, II category learning has been shown to be best with
      feedback delays of 500 ms compared to delays of 0 and 1000 ms, and highly
      impaired with delays of 2.5 s or longer. In contrast, RB learning is unaffected
      by any feedback delay up to 10 s. We propose a neurobiologically detailed theory
      of procedural learning that is sensitive to different feedback delays. The theory
      assumes that procedural learning is mediated by plasticity at cortical-striatal
      synapses that are modified by dopamine-mediated reinforcement learning. The model
      captures the time-course of the biochemical events in the striatum that cause
      synaptic plasticity, and thereby accounts for the empirical effects of various
      feedback delays on II category learning. 

PMID- 25071628
TI  - High-level context effects on spatial displacement: the effects of body
      orientation and language on memory.
AB  - Three decades of research suggests that cognitive simulation of motion is
      involved in the comprehension of object location, bodily configuration, and
      linguistic meaning. For example, the remembered location of an object associated
      with actual or implied motion is typically displaced in the direction of motion.
      In this paper, two experiments explore context effects in spatial displacement.
      They provide a novel approach to estimating the remembered location of an implied
      motion image by employing a cursor-positioning task. Both experiments examine how
      the remembered spatial location of a person is influenced by subtle differences
      in implied motion, specifically, by shifting the orientation of the person's body
      to face upward or downward, and by pairing the image with motion language that
      differed on intentionality, fell versus jumped. The results of Experiment 1, a
      survey-based experiment, suggest that language and body orientation influenced
      vertical spatial displacement. Results of Experiment 2, a task that used Adobe
      Flash and Amazon Mechanical Turk, showed consistent effects of body orientation
      on vertical spatial displacement but no effect of language. Our findings are in
      line with previous work on spatial displacement that uses a cursor-positioning
      task with implied motion stimuli. We discuss how different ways of simulating
      motion can influence spatial memory. 

PMID- 25071630
TI  - The influence of non-native language proficiency on speech perception
      performance.
AB  - The present study examined to what extent proficiency in a non-native language
      influences speech perception in noise. We explored how English proficiency
      affected native (Swedish) and non-native (English) speech perception in four
      speech reception threshold (SRT) conditions, including two energetic (stationary,
      fluctuating noise) and two informational (two-talker babble Swedish, two-talker
      babble English) maskers. Twenty-three normal-hearing native Swedish listeners
      participated, age between 28 and 64 years. The participants also performed
      standardized tests in English proficiency, non-verbal reasoning and working
      memory capacity. Our approach with focus on proficiency and the assessment of
      external as well as internal, listener-related factors allowed us to examine
      which variables explained intra- and interindividual differences in native and
      non-native speech perception performance. The main result was that in the non
      native target, the level of English proficiency is a decisive factor for speech
      intelligibility in noise. High English proficiency improved performance in all
      four conditions when the target language was English. The informational maskers
      were interfering more with perception than energetic maskers, specifically in the
      non-native target. The study also confirmed that the SRT's were better when
      target language was native compared to non-native. 

PMID- 25071631
TI  - Behavioral evidence for the role of cortical theta oscillations in determining
      auditory channel capacity for speech.
AB  - Studies on the intelligibility of time-compressed speech have shown flawless
      performance for moderate compression factors, a sharp deterioration for
      compression factors above three, and an improved performance as a result of
      "repackaging"-a process of dividing the time-compressed waveform into fragments,
      called packets, and delivering the packets in a prescribed rate. This intricate
      pattern of performance reflects the reliability of the auditory system in
      processing speech streams with different information transfer rates; the knee
      point of performance defines the auditory channel capacity. This study is
      concerned with the cortical computation principle that determines channel
      capacity. Oscillation-based models of speech perception hypothesize that the
      speech decoding process is guided by a cascade of oscillations with theta as
      "master," capable of tracking the input rhythm, with the theta cycles aligned
      with the intervocalic speech fragments termed theta-syllables; intelligibility
      remains high as long as theta is in sync with the input, and it sharply
      deteriorates once theta is out of sync. In the study described here the
      hypothesized role of theta was examined by measuring the auditory channel
      capacity of time-compressed speech undergone repackaging. For all speech speeds
      tested (with compression factors of up to eight), packaging rate at capacity
      equals 9 packets/s-aligned with the upper limit of cortical theta, thetamax
      (about 9 Hz)-and the packet duration equals the duration of one uncompressed
      theta-syllable divided by the compression factor. The alignment of both the
      packaging rate and the packet duration with properties of cortical theta suggests
      that the auditory channel capacity is determined by theta. Irrespective of speech
      speed, the maximum information transfer rate through the auditory channel is the
      information in one uncompressed theta-syllable long speech fragment per one
      thetamax cycle. Equivalently, the auditory channel capacity is 9 theta
      syllables/s. 

PMID- 25071632
TI  - An emotion-differentiated perspective on empathy with the emotion specific
      empathy questionnaire.
AB  - Empathy refers to the thoughts and feelings of one individual in response to the
      observed (emotional) experiences of another individual. Empathy, however, can
      occur toward persons experiencing a variety of emotions, raising the question of
      whether or not empathy can be emotion specific. This paper discusses theoretical
      and empirical support for the emotion specificity of empathy. We present a new
      measure, the Emotion Specific Empathy questionnaire, which assesses affective and
      cognitive empathy for the six basic emotions. This paper presents the measure's
      psychometric qualities and demonstrates, through a series of models, the
      discriminant validity between emotion specific empathies suggesting empathy is
      emotion specific. Results and implications are discussed. 

PMID- 25071634
TI  - A direct comparison of unconscious face processing under masking and interocular
      suppression.
AB  - Different combinations of forward and backward masking as well as interocular
      suppression have been used extensively to render stimuli invisible and to study
      those aspects of visual stimuli that are processed in the absence of conscious
      experience. Although the two techniques-masking vs. interocular suppression
      obviously differ both in their applications and mechanisms, only little effort
      has been made to compare them systematically. Yet, such a comparison is crucial:
      existing discrepancies in the extent of unconscious processing inferred from
      these two techniques must be reconciled, as our understanding of unconscious
      vision should be independent of the technique used to prevent visibility. Here,
      we studied similarities and differences between faces rendered invisible by
      masking vs. interocular suppression using a priming paradigm. By carefully
      equating stimulus strength across the two techniques, we analyzed the effects of
      face primes with the same viewpoint (repetition priming, Experiment 1) and of
      face primes with a different viewpoint (identity priming, Experiment 2) on the
      reaction times for a fame categorization task. Overall, we found that the
      magnitude of both repetition and identity priming largely depended on stimulus
      visibility. Moreover, when the primes were subjectively invisible, both
      repetition and identity priming were found to be qualitatively stronger under
      masking than under interocular suppression. Taken together, these results help
      refine our understanding of which level of visual processing each technique
      disrupts, and illustrate the importance of systematic methodological comparisons
      in the field of unconscious vision. 

PMID- 25071635
TI  - Learning to read as the formation of a dynamic system: evidence for dynamic
      stability in phonological recoding.
AB  - Two aspects of dynamic systems approaches that are pertinent to developmental
      models of reading are the emergence of a system with self-organizing
      characteristics, and its evolution over time to a stable state that is not easily
      modified or perturbed. The effects of dynamic stability may be seen in the
      differences obtained in the processing of print by beginner readers taught by
      different approaches to reading (phonics and text-centered), and more long-term
      effects on adults, consistent with these differences. However, there is little
      direct evidence collected over time for the same participants. In this study,
      lexicalized (implicit) phonological processing, and explicit phonological and
      letter-sound skills are further examined in a precocious reader whose early
      development at 3 and 5 years has been extensively described (Cognition, 2000,
      2004). At ages 10 and 14 years, comparisons were made with these earlier reports
      and skilled adult readers, using the same tasks for evidence of changes in
      reading processes. The results showed that along with an increase of reading
      accuracy and speed, her pattern of lexicalized phonological responses for reading
      did not change over time. Neither did her pattern of explicit phonological and
      letter-sound skills, aspects of which were inferior to her lexicalized
      phonological processing, and word reading. These results suggest dynamic
      stability of the word reading system. The early emergence of this system with
      minimal explicit skill development calls into question developmental reading
      theories that require such skills for learning to read. Currently, only the
      Knowledge Sources theory of reading acquisition can account for such findings.
      Consideration of these aspects of dynamic systems raise theoretical issues that
      could result in a paradigm shift with regard to best practice and intervention. 

PMID- 25071633
TI  - Temporal dynamics of sensorimotor integration in speech perception and
      production: independent component analysis of EEG data.
AB  - Activity in anterior sensorimotor regions is found in speech production and some
      perception tasks. Yet, how sensorimotor integration supports these functions is
      unclear due to a lack of data examining the timing of activity from these
      regions. Beta (~20 Hz) and alpha (~10 Hz) spectral power within the EEG MU rhythm
      are considered indices of motor and somatosensory activity, respectively. In the
      current study, perception conditions required discrimination (same/different) of
      syllables pairs (/ba/ and /da/) in quiet and noisy conditions. Production
      conditions required covert and overt syllable productions and overt word
      production. Independent component analysis was performed on EEG data obtained
      during these conditions to (1) identify clusters of MU components common to all
      conditions and (2) examine real-time event-related spectral perturbations (ERSP)
      within alpha and beta bands. 17 and 15 out of 20 participants produced left and
      right MU-components, respectively, localized to precentral gyri. Discrimination
      conditions were characterized by significant (pFDR < 0.05) early alpha event
      related synchronization (ERS) prior to and during stimulus presentation and later
      alpha event-related desynchronization (ERD) following stimulus offset. Beta ERD
      began early and gained strength across time. Differences were found between quiet
      and noisy discrimination conditions. Both overt syllable and word productions
      yielded similar alpha/beta ERD that began prior to production and was strongest
      during muscle activity. Findings during covert production were weaker than during
      overt production. One explanation for these findings is that MU-beta ERD indexes
      early predictive coding (e.g., internal modeling) and/or overt and covert
      attentional/motor processes. MU-alpha ERS may index inhibitory input to the
      premotor cortex from sensory regions prior to and during discrimination, while MU
      alpha ERD may index sensory feedback during speech rehearsal and production. 

PMID- 25071636
TI  - Moving from hand to mouth: echo phonology and the origins of language.
AB  - Although the sign languages in use today are full human languages, certain of the
      features they share with gestures have been suggested to provide information
      about possible origins of human language. These features include sharing common
      articulators with gestures, and exhibiting substantial iconicity in comparison to
      spoken languages. If human proto-language was gestural, the question remains of
      how a highly iconic manual communication system might have been transformed into
      a primarily vocal communication system in which the links between symbol and
      referent are for the most part arbitrary. The hypothesis presented here focuses
      on a class of signs which exhibit: "echo phonology," a repertoire of mouth
      actions which are characterized by "echoing" on the mouth certain of the
      articulatory actions of the hands. The basic features of echo phonology are
      introduced, and discussed in relation to various types of data. Echo phonology
      provides naturalistic examples of a possible mechanism accounting for part of the
      evolution of language, with evidence both of the transfer of manual actions to
      oral ones and the conversion of units of an iconic manual communication system
      into a largely arbitrary vocal communication system. 

PMID- 25071637
TI  - Effect of luminance noise on the object frequencies mediating letter
      identification.
AB  - PURPOSE: To determine if the same object frequency information mediates letter
      contrast threshold in the presence and absence of additive luminance noise (i.e.,
      "noise-invariant processing") for letters of different size. METHODS: Contrast
      thresholds for Sloan letters ranging in size from 0.9 to 1.8 log MAR were
      obtained from three visually normal observers under three paradigms: (1) high-
      and low-pass Gaussian filtered letters were presented against a uniform adapting
      field; (2) high- and low-pass Gaussian filtered letters were presented in
      additive white luminance noise; and (3) unfiltered letters were presented in high
      and low-pass Gaussian filtered luminance noise. A range of high- and low-pass
      filter cutoffs were used to limit selectively the object frequency content of the
      letters (paradigms 1 and 2) or noise (paradigm 3). The object frequencies
      mediating letter identification under each paradigm were derived from plots of
      log contrast threshold vs. log filter cutoff frequency. RESULTS: The object
      frequency band mediating letter identification systematically shifted to higher
      frequencies with increasing log MAR letter size under all three paradigms.
      However, the relationship between object frequency and letter size depended on
      the paradigm under which the measurements were obtained. The largest difference
      in object frequency among the paradigms was observed at 1.8 log MAR, where the
      addition of white noise nearly doubled the center frequency of the band of object
      frequencies mediating letter identification, compared to measurements made in the
      absence of noise. CONCLUSION: Noise can affect the object frequency band
      mediating letter contrast threshold, particularly for large letters, an effect
      that is likely due to strong masking of the low frequency letter components by
      low frequency noise checks. This finding indicates that noise-invariant
      processing cannot necessarily be assumed for large letters presented in white
      noise.

PMID- 25071638
TI  - Preparing learners with partly incorrect intuitive prior knowledge for learning.
AB  - Learners sometimes have incoherent and fragmented intuitive prior knowledge that
      is (partly) "incompatible" with the to-be-learned contents. Such knowledge in
      pieces can cause conceptual disorientation and cognitive overload while learning.
      We hypothesized that a pre-training intervention providing a generalized schema
      as a structuring framework for such knowledge in pieces would support
      (re)organizing-processes of prior knowledge and thus reduce unnecessary cognitive
      load during subsequent learning. Fifty-six student teachers participated in the
      experiment. A framework group underwent a pre-training intervention providing a
      generalized, categorical schema for categorizing primary learning strategies and
      related but different strategies as a cognitive framework for (re-)organizing
      their prior knowledge. Our control group received comparable factual information
      but no framework. Afterwards, all participants learned about primary learning
      strategies. The framework group claimed to possess higher levels of interest and
      self-efficacy, achieved higher learning outcomes, and learned more efficiently.
      Hence, providing a categorical framework can help overcome the barrier of
      incorrect prior knowledge in pieces. 

PMID- 25071639
TI  - Heuristics and biases: interactions among numeracy, ability, and reflectiveness
      predict normative responding.
AB  - In Stanovich's (2009a, 2011) dual-process theory, analytic processing occurs in
      the algorithmic and reflective minds. Thinking dispositions, indexes of
      reflective mind functioning, are believed to regulate operations at the
      algorithmic level, indexed by general cognitive ability. General limitations at
      the algorithmic level impose constraints on, and affect the adequacy of, specific
      strategies and abilities (e.g., numeracy). In a study of 216 undergraduates, the
      hypothesis that thinking dispositions and general ability moderate the
      relationship between numeracy (understanding of mathematical concepts and
      attention to numerical information) and normative responses on probabilistic
      heuristics and biases (HB) problems was tested. Although all three individual
      difference measures predicted normative responses, the numeracy-normative
      response association depended on thinking dispositions and general ability.
      Specifically, numeracy directly affected normative responding only at relatively
      high levels of thinking dispositions and general ability. At low levels of
      thinking dispositions, neither general ability nor numeric skills related to
      normative responses. Discussion focuses on the consistency of these findings with
      the hypothesis that the implementation of specific skills is constrained by
      limitations at both the reflective level and the algorithmic level,
      methodological limitations that prohibit definitive conclusions, and alternative
      explanations. 

PMID- 25071640
TI  - Ego, drives, and the dynamics of internal objects.
AB  - This paper addresses the relationship between the ego, id, and internal objects.
      While ego psychology views the ego as autonomous of the drives, a less well-known
      alternative position views the ego as constituted by the drives. Based on Freud's
      ego-instinct account, this position has developed into a school of thought which
      postulates that the drives act as knowers. Given that there are multiple drives,
      this position proposes that personality is constituted by multiple knowers.
      Following on from Freud, the ego is viewed as a composite sub-set of the
      instinctual drives (ego-drives), whereas those drives cut off from expression
      form the id. The nature of the "self" is developed in terms of identification and
      the possibility of multiple personalities is also established. This account is
      then extended to object-relations and the explanatory value of the ego-drive
      account is discussed in terms of the addressing the nature of ego-structures and
      the dynamic nature of internal objects. Finally, the impact of psychological
      conflict and the significance of repression for understanding the nature of
      splits within the psyche are also discussed. 

PMID- 25071641
TI  - Developmental differences in masked form priming are not driven by vocabulary
      growth.
AB  - As children develop into skilled readers, they are able to more quickly and
      accurately distinguish between words with similar visual forms (i.e., they
      develop precise lexical representations). The masked form priming lexical
      decision task is used to test the precision of lexical representations. In this
      paradigm, a prime (which differs by one letter from the target) is briefly
      flashed before the target is presented. Participants make a lexical decision to
      the target. Primes can facilitate reaction time by partially activating the
      lexical entry for the target. If a prime is unable to facilitate reaction time,
      it is assumed that participants have a precise orthographic representation of the
      target and thus the prime is not a close enough match to activate its lexical
      entry. Previous developmental work has shown that children and adults' lexical
      decision times are facilitated by form primes preceding words from small
      neighborhoods (i.e., very few words can be formed by changing one letter in the
      original word; low N words), but only children are facilitated by form primes
      preceding words from large neighborhoods (high N words). It has been hypothesized
      that written vocabulary growth drives the increase in the precision of the
      orthographic representations; children may not know all of the neighbors of the
      high N words, making the words effectively low N for them. We tested this
      hypothesis by (1) equating the effective orthographic neighborhood size of the
      targets for children and adults and (2) testing whether age or vocabulary size
      was a better predictor of the extent of form priming. We found priming
      differences even when controlling for effective neighborhood size. Furthermore,
      age was a better predictor of form priming effects than was vocabulary size. Our
      findings provide no support for the hypothesis that growth in written vocabulary
      size gives rise to more precise lexical representations. We propose that the
      development of spelling ability may be a more important factor. 

PMID- 25071642
TI  - On agent-based modeling and computational social science.
AB  - In the first part of the paper, the field of agent-based modeling (ABM) is
      discussed focusing on the role of generative theories, aiming at explaining
      phenomena by growing them. After a brief analysis of the major strengths of the
      field some crucial weaknesses are analyzed. In particular, the generative power
      of ABM is found to have been underexploited, as the pressure for simple recipes
      has prevailed and shadowed the application of rich cognitive models. In the
      second part of the paper, the renewal of interest for Computational Social
      Science (CSS) is focused upon, and several of its variants, such as deductive,
      generative, and complex CSS, are identified and described. In the concluding
      remarks, an interdisciplinary variant, which takes after ABM, reconciling it with
      the quantitative one, is proposed as a fundamental requirement for a new program
      of the CSS. 

PMID- 25071643
TI  - Not all "distractor" tags are created equal: using a search asymmetry to
      dissociate the inter-trial effects caused by different forms of distractors.
AB  - In a typical pop-out task, there is one target and a varying number of distractor
      stimuli. Now imagine a target-absent display in the context of a pop-out task:
      all items are identical, and it is decidedly easy to conclude that all items in
      the display are distractors, precisely because there is no target to select on
      that display. One may be tempted to say that, as far as the attention system is
      concerned, these two types of distractors are the same: target-present
      distractors and target-absent distractors. The present study proposes that this
      is actually not the case. Target-absent distractors can sometimes produce inter
      trial effects that their close-cousins, the target-present distractors, cannot.
      We used a letters/numbers categorical oddball task to demonstrate this
      difference. The results are interpreted in the context of recent findings in
      cognitive neuroscience as well as cognitive modeling. 

PMID- 25071644
TI  - An architecturally constrained model of random number generation and its
      application to modeling the effect of generation rate.
AB  - Random number generation (RNG) is a complex cognitive task for human subjects,
      requiring deliberative control to avoid production of habitual, stereotyped
      sequences. Under various manipulations (e.g., speeded responding, transcranial
      magnetic stimulation, or neurological damage) the performance of human subjects
      deteriorates, as reflected in a number of qualitatively distinct, dissociable
      biases. For example, the intrusion of stereotyped behavior (e.g., counting)
      increases at faster rates of generation. Theoretical accounts of the task
      postulate that it requires the integrated operation of multiple, computationally
      heterogeneous cognitive control ("executive") processes. We present a
      computational model of RNG, within the framework of a novel, neuropsychologically
      inspired cognitive architecture, ESPro. Manipulating the rate of sequence
      generation in the model reproduced a number of key effects observed in empirical
      studies, including increasing sequence stereotypy at faster rates. Within the
      model, this was due to time limitations on the interaction of supervisory control
      processes, namely, task setting, proposal of responses, monitoring, and response
      inhibition. The model thus supports the fractionation of executive function into
      multiple, computationally heterogeneous processes. 

PMID- 25071645
TI  - Effects of social gaze on visual-spatial imagination.
AB  - Previous research suggests that closing one's eyes or averting one's gaze from
      another person can benefit visual-spatial imagination by interrupting cognitive
      demands associated with face-to-face interaction (Markson and Paterson, 2009).
      The present study further investigated this influence of social gaze on adults'
      visual-spatial imagination, using the matrix task (Kerr, 1987, 1993).
      Participants mentally kept track of a pathway through an imaginary 2-dimensional
      (2D) or 3-dimensional (3D) matrix. Concurrent with this task, participants either
      kept their eyes closed or maintained eye contact with another person, mutual gaze
      with a person whose eyes were obscured (by wearing dark glasses), or
      unreciprocated gaze toward the face of a person whose own gaze was averted or
      whose face was occluded (by placing a paper bag over her head). Performance on
      the 2D task was poorest in the eye contact condition, and did not differ between
      the other gaze conditions, which produced ceiling performance. However, the more
      difficult 3D task revealed clear effects of social gaze. Performance on the 3D
      task was poorest for eye contact, better for mutual gaze, and equally better
      still for the unreciprocated gaze and eye-closure conditions. The findings reveal
      the especially disruptive influence of eye contact on concurrent visual-spatial
      imagination and a benefit for cognitively demanding tasks of disengaging eye
      contact during face-to-face interaction. 

PMID- 25071646
TI  - Exploring the role of hand gestures in learning novel phoneme contrasts and
      vocabulary in a second language.
AB  - Co-speech hand gestures are a type of multimodal input that has received
      relatively little attention in the context of second language learning. The
      present study explored the role that observing and producing different types of
      gestures plays in learning novel speech sounds and word meanings in an L2. Naive
      English-speakers were taught two components of Japanese-novel phonemic vowel
      length contrasts and vocabulary items comprised of those contrasts-in one of four
      different gesture conditions: Syllable Observe, Syllable Produce, Mora Observe,
      and Mora Produce. Half of the gestures conveyed intuitive information about
      syllable structure, and the other half, unintuitive information about Japanese
      mora structure. Within each Syllable and Mora condition, half of the participants
      only observed the gestures that accompanied speech during training, and the other
      half also produced the gestures that they observed along with the speech. The
      main finding was that participants across all four conditions had similar
      outcomes in two different types of auditory identification tasks and a vocabulary
      test. The results suggest that hand gestures may not be well suited for learning
      novel phonetic distinctions at the syllable level within a word, and thus,
      gesture-speech integration may break down at the lowest levels of language
      processing and learning. 

PMID- 25071648
TI  - Been there before? Examining "familiarity" as a moderator for discriminating
      between true and false intentions.
AB  - Prospection is thinking about possible future states of the world. Commitment to
      perform a future action-commonly referred to as intention-is a specific type of
      prospection. This knowledge is relevant when trying to assess whether a stated
      intention is a lie or the truth. An important observation is that thinking of,
      and committing to, future actions often evoke vivid and detailed mental images.
      One factor that affects how specific a person experiences these simulations is
      location-familiarity. The purpose of this study was to examine to what extent
      location-familiarity moderates how liars and truth tellers describe a mental
      image in an investigative interview. Liars were instructed to plan a criminal act
      and truth tellers were instructed to plan a non-criminal act. Before they could
      carry out these acts, the participants were intercepted and interviewed about the
      mental images they may have had experienced in this planning phase. Truth tellers
      told the truth whereas liars used a cover story to mask their criminal
      intentions. As predicted, the results showed that the truth tellers reported a
      mental image significantly more often than the liars. If a mental image was
      reported, the content of the descriptions did not differ between liars and truth
      tellers. In a post interview questionnaire, the participants rated the vividness
      (i.e., content and clarity) of their mental images. The ratings revealed that the
      truth tellers had experienced their mental images more vividly during the
      planning phase than the liars. In conclusion, this study indicates that both
      prototypical and specific representations play a role in prospection. Although
      location-familiarity did not moderate how liars and truth tellers describe their
      mental images of the future, this study allows some interesting insights into
      human future thinking. How these findings can be helpful for distinguishing
      between true and false intentions will be discussed. 

PMID- 25071647
TI  - Early recurrent feedback facilitates visual object recognition under challenging
      conditions.
AB  - Standard models of the visual object recognition pathway hold that a largely
      feedforward process from the retina through inferotemporal cortex leads to object
      identification. A subsequent feedback process originating in frontoparietal areas
      through reciprocal connections to striate cortex provides attentional support to
      salient or behaviorally-relevant features. Here, we review mounting evidence that
      feedback signals also originate within extrastriate regions and begin during the
      initial feedforward process. This feedback process is temporally dissociable from
      attention and provides important functions such as grouping, associational
      reinforcement, and filling-in of features. Local feedback signals operating
      concurrently with feedforward processing are important for object identification
      in noisy real-world situations, particularly when objects are partially occluded,
      unclear, or otherwise ambiguous. Altogether, the dissociation of early and late
      feedback processes presented here expands on current models of object
      identification, and suggests a dual role for descending feedback projections. 

PMID- 25071649
TI  - Hearing impairment and audiovisual speech integration ability: a case study
      report.
AB  - Research in audiovisual speech perception has demonstrated that sensory factors
      such as auditory and visual acuity are associated with a listener's ability to
      extract and combine auditory and visual speech cues. This case study report
      examined audiovisual integration using a newly developed measure of capacity in a
      sample of hearing-impaired listeners. Capacity assessments are unique because
      they examine the contribution of reaction-time (RT) as well as accuracy to
      determine the extent to which a listener efficiently combines auditory and visual
      speech cues relative to independent race model predictions. Multisensory speech
      integration ability was examined in two experiments: an open-set sentence
      recognition and a closed set speeded-word recognition study that measured
      capacity. Most germane to our approach, capacity illustrated speed-accuracy
      tradeoffs that may be predicted by audiometric configuration. Results revealed
      that some listeners benefit from increased accuracy, but fail to benefit in terms
      of speed on audiovisual relative to unisensory trials. Conversely, other
      listeners may not benefit in the accuracy domain but instead show an audiovisual
      processing time benefit. 

PMID- 25071650
TI  - The Einstellung effect in anagram problem solving: evidence from eye movements.
AB  - The Einstellung effect is the counterintuitive finding that prior experience or
      domain-specific knowledge can under some circumstances interfere with problem
      solving performance. This effect has been demonstrated in several domains of
      expertise including medicine and chess. In the present study we explored this
      effect in the context of a simplified anagram problem solving task. Participants
      solved anagram problems while their eye movements were monitored. Each problem
      consisted of six letters: a central three-letter string whose letters were part
      of the solution word, and three additional individual letters. Participants were
      informed that one of the individual letters was a distractor letter and were
      asked to find a five-letter solution word. In order to examine the impact of
      stimulus familiarity on problem solving performance and eye movements, the
      central letter string was presented either as a familiar three-letter word, or
      the letters were rearranged to form a three-letter nonword. Replicating the
      classic Einstellung effect, overall performance was better for nonword than word
      trials. However, participants' eye movements revealed a more complex pattern of
      both interference and facilitation as a function of the familiarity of the
      central letter string. Specifically, word trials resulted in shorter viewing
      times on the central letter string and longer viewing times on the individual
      letters than nonword trials. These findings suggest that while participants were
      better able to encode and maintain the meaningful word stimuli in working memory,
      they found it more challenging to integrate the individual letters into the
      central letter string when it was presented as a word. 

PMID- 25071651
TI  - The architecture of visual narrative comprehension: the interaction of narrative
      structure and page layout in understanding comics.
AB  - How do people make sense of the sequential images in visual narratives like
      comics? A growing literature of recent research has suggested that this
      comprehension involves the interaction of multiple systems: The creation of
      meaning across sequential images relies on a "narrative grammar" that packages
      conceptual information into categorical roles organized in hierarchic
      constituents. These images are encapsulated into panels arranged in the layout of
      a physical page. Finally, how panels frame information can impact both the
      narrative structure and page layout. Altogether, these systems operate in
      parallel to construct the Gestalt whole of comprehension of this visual language
      found in comics. 

PMID- 25071652
TI  - Three-year-olds' theories of mind are symbolic but of low complexity.

PMID- 25071653
TI  - Attention to the body depends on eye-in-orbit position.
AB  - Attentional selectivity in touch is modulated by the position of the body in
      external space. For instance, during endogenous attention tasks in which tactile
      stimuli are presented to the hands, the effect of attention is reduced when the
      hands are placed far apart than when they are close together and when the hands
      are crossed as compared to when they are placed in their anatomical position.
      This suggests that both somatotopic and external spatial reference frames coding
      the hands' locations contribute to the spatial selection of the relevant hand.
      Here we investigate whether tactile selection of hands is also modulated by the
      position of other body parts, not directly involved in tactile perception, such
      as eye-in-orbit (gaze direction). We asked participants to perform the same
      sustained tactile attention task while gazing laterally toward an eccentric
      fixation point (Eccentric gaze) or toward a central fixation point (Central
      gaze). Event-related potentials recorded in response to tactile non-target
      stimuli presented to the attended or unattended hand were compared as a function
      of gaze direction (Eccentric vs. Central conditions). Results revealed that
      attentional modulations were reduced in the Eccentric gaze condition as compared
      to the Central gaze condition in the time range of the Nd component (200-260 ms
      post-stimulus), demonstrating for the first time that the attentional selection
      of one of the hands is affected by the position of the eye in the orbit.
      Directing the eyes toward an eccentric position might be sufficient to create a
      misalignment between external and somatotopic frames of references reducing
      tactile attention. This suggests that the eye-in-orbit position contributes to
      the spatial selection of the task relevant body part. 

PMID- 25071655
TI  - Attentional biases toward threat: the concomitant presence of difficulty of
      disengagement and attentional avoidance in low trait anxious individuals.
AB  - Attentional biases toward threats (ABTs) have been described in high anxious
      individuals and in clinical samples whereas they have been rarely reported in non
      clinical samples (Bar-Haim et al., 2007; Cisler and Koster, 2010). Three kinds of
      ABTs have been identified (facilitation, difficulty of disengagement, and
      avoidance) but their mechanisms and time courses are still unclear. This study
      aimed to understand ABTs mechanisms and timing in low trait anxiety (LTA) and
      high trait anxiety (HTA) anxious individuals. In particular, in an exogenous
      cueing task we used threatening or neutral stimuli as peripheral cues with three
      presentation times (100, 200, or 500 ms). The main results showed that HTA
      individuals have an attentional facilitation bias at 100 ms (likely automatic in
      nature) whereas LTA individuals show attentional avoidance and difficulty to
      disengage from threatening stimuli at 200 ms (likely related to a strategic
      processing). Such findings demonstrate that threat biases attention with specific
      mechanisms and time courses, and that anxiety levels modulate attention
      allocation. 

PMID- 25071654
TI  - Decision and dopaminergic system: an ERPs study of Iowa gambling task in
      Parkinson's disease.
AB  - Recent researches reported behavioral and emotional impairment in Parkinson's
      disease (PD), even in the earliest stages. This impairment affects also decision
      making and learning processes. The Iowa gambling task (IGT) is commonly used to
      examine the decision-making capacity. The purpose of the present study was to
      investigate the neural correlates of feedback evaluation in the decision-making
      process into a learning context, using IGT and event-related potentials (ERPs) in
      a group of non-demented medicated PD patients. Fifteen PD patients and 15 healthy
      controls were recruited for the study. PD patients were administrated a basic
      neuropsychological assessment oriented to exclude cognitive impairments. Both
      groups underwent the computerized IGT during electroencephalography (EEG)
      registration. To analyse ERPs, continuous EEG data were epoched within a time
      window starting 1000 ms before and ending 1000 ms after feedback presentation and
      averaged separately for positive (i.e., win condition) and negative (i.e., loss
      condition) feedbacks. Behavioral data revealed a significant lower performance of
      PD patients (p < 0.05) compared with the controls. While controls demonstrated a
      correct feedback evaluation, PD patients did not show any learning, selecting
      more disadvantageous decks even in the last part of task. Furthermore, ERPs
      results revealed that controls showed a significant difference (p < 0.05) in ERPs
      morphology recorded after the win and the loss conditions, suggesting that
      positive and negative feedbacks were differently evaluated and processed. PD
      patients showed a different pattern: their ERPs morphology was the same for
      positive and negative feedback. Interestingly, our ERPs results suggest that in
      PD patients an incorrect evaluation of context-relevant outcomes could be the
      reason of a poor performance in decision-making tasks, and could explain
      cognitive and behavioral problems related to impulse control disorder. 

PMID- 25071656
TI  - Devil in the details? Developmental dyslexia and visual long-term memory for
      details.
AB  - Cognitive theories on causes of developmental dyslexia can be divided into
      language-specific and general accounts. While the former assume that words are
      special in that associated processing problems are rooted in language-related
      cognition (e.g., phonology) deficits, the latter propose that dyslexia is rather
      rooted in a general impairment of cognitive (e.g., visual and/or auditory)
      processing streams. In the present study, we examined to what extent dyslexia
      (typically characterized by poor orthographic representations) may be associated
      with a general deficit in visual long-term memory (LTM) for details. We compared
      object- and detail-related visual LTM performance (and phonological skills)
      between dyslexic primary school children and IQ-, age-, and gender-matched
      controls. The results revealed that while the overall amount of LTM errors was
      comparable between groups, dyslexic children exhibited a greater portion of
      detail-related errors. The results suggest that not only phonological, but also
      general visual resolution deficits in LTM may play an important role in
      developmental dyslexia. 

PMID- 25071657
TI  - Dynamical systems analysis applied to working memory data.
AB  - In the present paper we investigate weekly fluctuations in the working memory
      capacity (WMC) assessed over a period of 2 years. We use dynamical system
      analysis, specifically a second order linear differential equation, to model
      weekly variability in WMC in a sample of 112 9th graders. In our longitudinal
      data we use a B-spline imputation method to deal with missing data. The results
      show a significant negative frequency parameter in the data, indicating a
      cyclical pattern in weekly memory updating performance across time. We use a
      multilevel modeling approach to capture individual differences in model
      parameters and find that a higher initial performance level and a slower
      improvement at the MU task is associated with a slower frequency of oscillation.
      Additionally, we conduct a simulation study examining the analysis procedure's
      performance using different numbers of B-spline knots and values of time delay
      embedding dimensions. Results show that the number of knots in the B-spline
      imputation influence accuracy more than the number of embedding dimensions. 

PMID- 25071658
TI  - What pops out in positional priming of pop-out: insights from event-related EEG
      lateralizations.
AB  - It is well established that, in visual pop-out search, reaction time (RT)
      performance is influenced by cross-trial repetitions versus changes of target
      defining attributes. One instance of this is referred to as "positional priming
      of pop-out" (pPoP; Maljkovic and Nakayama, 1996). In positional PoP paradigms,
      the processing of the current target is examined depending on whether it occurs
      at the previous target or a previous distractor location, relative to a
      previously empty location ("neutral" baseline), permitting target facilitation
      and distractor inhibition to be dissociated. The present study combined RT
      measures with specific sensory- and motor-driven event-related lateralizations to
      track the time course of four distinct processing levels as a function of the
      target's position across consecutive trials. The results showed that, relative to
      targets at previous target and "neutral" locations, the appearance of a target at
      a previous distractor location was associated with a delayed build-up of the
      posterior contralateral negativity wave, indicating that distractor positions are
      suppressed at early stages of visual processing. By contrast, presentation of a
      target at a previous target, relative to "neutral" and distractor locations,
      modulated the elicitation of the subsequent stimulus-locked lateralized readiness
      potential wave, indicating that post-selective response selection is facilitated
      if the target occurred at the same position as on the previous trial. Overall,
      the results of present study provide electrophysiological evidence for the idea
      that target location priming (RT benefits) does not originate from an enhanced
      coding of target saliency at repeated (target) locations; instead, they arise
      (near-) exclusively from processing levels subsequent to focal-attentional target
      selection. 

PMID- 25071659
TI  - How does this make you feel? A comparison of four affect induction procedures.
AB  - Affect is a fundamental aspect of the human mind. An increasing number of
      experiments attempt to examine the influence of affect on other psychological
      phenomena. To accomplish this research, it is necessary to experimentally modify
      participants' affective states. In the present experiment, we compared the
      efficacy of four commonly used affect induction procedures. Participants (38
      healthy undergraduate students: 18 males) were randomly assigned to either a
      pleasant or an unpleasant affect induction group, and then underwent four
      different affect induction procedures: (1) recall of an affectively salient event
      accompanied by affectively congruent music, (2) script-driven guided imagery, (3)
      viewing images while listening to affectively congruent music, and (4) posing
      affective facial actions, body postures, and vocal expressions. All four affect
      induction methods were successful in inducing both pleasant and unpleasant
      affective states. The viewing image with music and recall with music procedures
      were most effective in enhancing positive affect, whereas the viewing image with
      music procedure was most effective in enhancing negative affect. Implications for
      the scientific study of affect are discussed. 

PMID- 25071660
TI  - Context influences conscious appraisal of cross situational statistical learning.
AB  - Previous research in cross-situational statistical learning has established that
      people can track statistical information across streams in order to map nonce
      words to their referent objects (Yu and Smith, 2007). Under some circumstances,
      learners are able to acquire multiple mappings for a single object (e.g.,
      Yurovsky and Yu, 2008). Here we explore whether having a contextual cue
      associated with a new mapping may facilitate this process, or the conscious
      awareness of learning. Using a cross-situational statistical learning paradigm,
      in which learners could form both 1:1 and 2:1 word-object mappings over two
      phases of learning, we collected confidence ratings during familiarization and
      provided a retrospective test to gage learning. In Condition 1, there were no
      contextual cues to indicate a change in mappings (baseline). Conditions 2 and 3
      added contextual cues (a change in speaker voice or explicit instructions,
      respectively) to the second familiarization phase to determine their effects on
      the trajectory of learning. While contextual cues did not facilitate acquisition
      of 2:1 mappings as assessed by retrospective measures, confidence ratings for
      these mappings were significantly higher in contextual cue conditions compared to
      the baseline condition with no cues. These results suggest that contextual cues
      corresponding to changes in the input may influence the conscious awareness of
      learning. 

PMID- 25071661
TI  - The visual magnocellular deficit in Chinese-speaking children with developmental
      dyslexia.
AB  - Many alphabetic studies have evidenced that individuals with developmental
      dyslexia (DD) have deficits in visual magnocellular (M) pathway. However, there
      are few studies to investigate the M function of Chinese DD. Chinese is a
      logographic language, and Chinese characters are complicated in structure. Visual
      skills and orthographic processing abilities are particularly important for
      efficient reading in Chinese as compared to alphabetic languages. Therefore, it
      is necessary to investigate the visual M function of Chinese DD and whether the M
      function was associated with orthographic skills. In the present study, 26
      dyslexic children (mean age: 10.03 years) and 27 age-matched normal children
      (mean age: 10.37 years) took part in a coherent motion (CM) detection task and an
      orthographic awareness test. The results showed that dyslexic children had a
      significantly higher threshold than age-matched children in CM detection task.
      Meanwhile, children with DD responded more slowly in orthographic awareness test,
      although the group difference was marginally significant. The results suggested
      that Chinese dyslexics had deficits both in visual M pathway processing and
      orthographic processing. In order to investigate the relationship between M
      function and orthographic skills, we made a correlation analysis between CM
      threshold and orthographic awareness by merging performance of dyslexic children
      and age-matched children. The results revealed that CM thresholds were positively
      correlated with reaction times in orthographic awareness test, suggesting that
      better M function was related to better orthographic processing skills. 

PMID- 25071662
TI  - Effects of angular shift transformations between movements and their visual
      feedback on coordination in unimanual circling.
AB  - Tool actions are characterized by a transformation between movements and their
      resulting consequences in the environment. This transformation has to be taken
      into account when tool actions are planned and executed. We investigated how
      angular shift transformations between circling movements and their visual
      feedback affect the coordination of this feedback with visual events in the
      environment. We used a task that required participants to coordinate the visual
      feedback of a circular hand movement (presented on the right side of a screen)
      with a circling stimulus (presented on the left side of a screen). Four stimulus
      visual feedback relations were instructed: same or different rotations of
      stimulus and visual feedback, either in same or different y-directions. Visual
      speed was varied in three levels (0.8, 1, and 1.2 Hz). The movement-visual
      feedback relation was manipulated using eight angular shifts: (-180, -135, -90, 
      45, 0, 45, 90, and 135 degrees ). Participants were not able to perform the
      different rotation/different y-direction pattern, but instead fell into the
      different rotation/same y-direction pattern. The different rotation/same y
      direction pattern and the same rotation/same y-direction pattern were performed
      equally well, performance was worse in the same rotation/different y-direction
      pattern. Best performance was observed with angular shifts 0 and -45 degrees  and
      performance declined with larger angular shifts. Further, performance was better
      with negative angular shifts than with positive angular shifts. Participants did
      not fully take the angular shift transformation into account: when the angular
      shifts were negative the visual feedback was more in advance, and when angular
      shifts were positive the visual feedback was less in advance of the stimulus than
      in 0 degrees  angular shift. In conclusion, the presence and the magnitude of
      angular shift transformations affect performance. Internal models do not fully
      take the shift transformation into account. 

PMID- 25071663
TI  - The transition in the ventral stream from feature to real-world entity
      representations.
AB  - We propose that the ventral visual pathway of human and non-human primates is
      organized into three levels: (1) ventral retinotopic cortex including what is
      known as TEO in the monkey but corresponds to V4A and PITd/v, and the phPIT
      cluster in humans, (2) area TE in the monkey and its homolog LOC and neighboring
      fusiform regions, and more speculatively, (3) TGv in the monkey and its possible
      human equivalent, the temporal pole. We attribute to these levels the visual
      representations of features, partial real-world entities (RWEs), and known,
      complete RWEs, respectively. Furthermore, we propose that the middle level, TE
      and its homolog, is organized into three parallel substreams, lower bank STS,
      dorsal convexity of TE, and ventral convexity of TE, as are their corresponding
      human regions. These presumably process shape in depth, 2D shape and material
      properties, respectively, to construct RWE representations. 

PMID- 25071665
TI  - Metastable structures and size effects in small group dynamics.
AB  - In his seminal works on group dynamics Bion defined a specific therapeutic
      setting allowing psychoanalytic observations on group phenomena. In describing
      the setting he proposed that the group was where his voice arrived. This physical
      limit was later made operative by assuming that the natural dimension of a
      therapeutic group is around 12 people. Bion introduced a theory of the group
      aspects of the mind in which proto-mental individual states spontaneously evolve
      into shared psychological states that are characterized by a series of features:
      (1) they emerge as a consequence of the natural tendency of (both conscious and
      unconscious) emotions to combine into structured group patterns; (2) they have a
      certain degree of stability in time; (3) they tend to alternate so that the
      dissolution of one is rapidly followed by the emergence of another; (4) they can
      be described in qualitative terms according to the nature of the emotional mix
      that dominates the state, in structural terms by a kind of typical "leadership"
      pattern, and in "cognitive" terms by a set of implicit expectations that are
      helpful in explaining the group behavior (i.e., the group behaves "as if" it was
      assuming that). Here we adopt a formal approach derived from Socio-physics in
      order to explore some of the structural and dynamic properties of this small
      group dynamics. We will described data from an analytic DS model simulating small
      group interactions of agents endowed with a very simplified emotional and
      cognitive dynamic in order to assess the following main points: (1) are
      metastable collective states allowed to emerge in the model and if so, under
      which conditions in the parameter space? (2) can these states be differentiated
      in structural terms? (3) to what extent are the emergent dynamic features of the
      systems dependent of the system size? We will finally discuss possible future
      applications of the quantitative descriptions of the interaction structure in the
      small group clinical setting. 

PMID- 25071664
TI  - Associative memory advantage in grapheme-color synesthetes compared to older, but
      not young adults.
AB  - People with grapheme-color synesthesia perceive enriched experiences of colors in
      response to graphemes (letters, digits). In this study, we examined whether these
      synesthetes show a generic associative memory advantage for stimuli that do not
      elicit a synesthetic color. We used a novel between group design (14 young
      synesthetes, 14 young, and 14 older adults) with a self-paced visual associative
      learning paradigm and subsequent retrieval (immediate and delayed). Non
      synesthesia inducing, achromatic fractal pair-associates were manipulated in
      visual similarity (high and low) and corresponded to high and low memory load
      conditions. The main finding was a learning and retrieval advantage of
      synesthetes relative to older, but not to younger, adults. Furthermore, the
      significance testing was supported with effect size measures and power
      calculations. Differences between synesthetes and older adults were found during
      dissimilar pair (high memory load) learning and retrieval at immediate and
      delayed stages. Moreover, we found a medium size difference between synesthetes
      and young adults for similar pair (low memory load) learning. Differences between
      young and older adults were also observed during associative learning and
      retrieval, but were of medium effect size coupled with low power. The results
      show a subtle associative memory advantage in synesthetes for non-synesthesia
      inducing stimuli, which can be detected against older adults. They also indicate
      that perceptual mechanisms (enhanced in synesthesia, declining as part of the
      aging process) can translate into a generic associative memory advantage, and may
      contribute to associative deficits accompanying healthy aging. 

PMID- 25071666
TI  - Prosody in the hands of the speaker.
AB  - In everyday life, speech is accompanied by gestures. In the present study, two
      experiments tested the possibility that spontaneous gestures accompanying speech
      carry prosodic information. Experiment 1 showed that gestures provide prosodic
      information, as adults are able to perceive the congruency between low-pass
      filtered-thus unintelligible-speech and the gestures of the speaker. Experiment 2
      shows that in the case of ambiguous sentences (i.e., sentences with two
      alternative meanings depending on their prosody) mismatched prosody and gestures
      lead participants to choose more often the meaning signaled by gestures. Our
      results demonstrate that the prosody that characterizes speech is not a modality
      specific phenomenon: it is also perceived in the spontaneous gestures that
      accompany speech. We draw the conclusion that spontaneous gestures and speech
      form a single communication system where the suprasegmental aspects of spoken
      language are mapped to the motor-programs responsible for the production of both
      speech sounds and hand gestures. 

PMID- 25071667
TI  - Predictors of depression, stress, and anxiety among non-tenure track faculty.
AB  - Nationwide in the United States, 70% of faculty members in higher education are
      employed off the tenure-track. Nearly all of these non-tenure-track (NTT)
      appointments share a quality that may produce stress for those who hold them:
      contingency. Most NTT appointments are contingent on budget, enrollment, or both,
      and the majority of contingent faculty members are hired for one quarter or
      semester at a time. Significant research has investigated the effects of
      contingency on teaching, students, departments, colleges, and universities;
      however, little research has focused on the psychological experiences of NTT
      faculty. The current study examined perceptions of workplace stressors and harm,
      organizational commitment, common coping mechanisms, and depression, anxiety and
      stress among NTT faculty using a longitudinal design that spanned 2-4 months.
      Results indicate that NTT faculty perceive unique stressors at work that are
      related to their contingent positions. Specific demographic characteristics and
      coping strategies, inability to find a permanent faculty position, and commitment
      to one's organization predispose NTT faculty to perceive greater harm and more
      sources of stress in their workplaces. Demographic characteristics, lower income,
      inability to find a permanent faculty position, disengagement coping mechanisms
      (e.g., giving up, denial), and organizational commitment were associated with the
      potential for negative outcomes, particularly depression, anxiety, and stress.
      Our findings suggest possibilities for institutional intervention. Overall, we
      argue that universities would be well-served by attending to the needs of NTT
      faculty on campus in order to mitigate negative outcomes for institutions,
      students, and faculty. 

PMID- 25071668
TI  - Back to the future: synaesthesia could be due to associative learning.

PMID- 25071669
TI  - How does literacy break mirror invariance in the visual system?

PMID- 25071670
TI  - Well-being in amyotrophic lateral sclerosis: a pilot experience sampling study.
AB  - OBJECTIVE: The aim of this longitudinal study was to identify predictors of
      instantaneous well-being in patients with amyotrophic lateral sclerosis (ALS).
      Based on flow theory well-being was expected to be highest when perceived demands
      and perceived control were in balance, and that thinking about the past would be
      a risk factor for rumination which would in turn reduce well-being. METHODS:
      Using the experience sampling method, data on current activities, associated
      aspects of perceived demands, control, and well-being were collected from 10
      patients with ALS three times a day for two weeks. RESULTS: RESULTS show that
      perceived control was uniformly and positively associated with well-being, but
      that demands were only positively associated with well-being when they were
      perceived as controllable. Mediation analysis confirmed thinking about the past,
      but not thinking about the future, to be a risk factor for rumination and reduced
      well-being. DISCUSSION: Findings extend our knowledge of factors contributing to
      well-being in ALS as not only perceived control but also perceived demands can
      contribute to well-being. They further show that a focus on present experiences
      might contribute to increased well-being.

PMID- 25071672
TI  - A proposed integration of the expert performance and individual differences
      approaches to the study of elite performance.

PMID- 25071673
TI  - An adaptive toolbox approach to the route to expertise in sport.
AB  - Expertise is characterized by fast decision-making which is highly adaptive to
      new situations. Here we propose that athletes use a toolbox of heuristics which
      they develop on their route to expertise. The development of heuristics occurs
      within the context of the athletes' natural abilities, past experiences,
      developed skills, and situational context, but does not pertain to any of these
      factors separately. This is a novel approach because it integrates separate
      factors into a comprehensive heuristic description. The novelty of this approach
      lies within the integration of separate factors determining expertise into a
      comprehensive heuristic description. It is our contention that talent
      identification methods and talent development models should therefore be geared
      toward the assessment and development of specific heuristics. Specifically, in
      addition to identifying and developing separate natural abilities and skills as
      per usual, heuristics should be identified and developed. The application of
      heuristics to talent and expertise models can bring the field one step away from
      dichotomized models of nature and nurture toward a comprehensive approach to the
      route to expertise. 

PMID- 25071671
TI  - Evidence-informed physical therapy management of performance-related
      musculoskeletal disorders in musicians.
AB  - Playing a musical instrument at an elite level is a highly complex motor skill.
      The regular daily training loads resulting from practice, rehearsals and
      performances place great demands on the neuromusculoskeletal systems of the body.
      As a consequence, performance-related musculoskeletal disorders (PRMDs) are
      globally recognized as common phenomena amongst professional orchestral
      musicians. These disorders create a significant financial burden to individuals
      and orchestras as well as lead to serious consequences to the musicians'
      performance and ultimately their career. Physical therapists are experts in
      treating musculoskeletal injuries and are ideally placed to apply their skills to
      manage PRMDs in this hyper-functioning population, but there is little available
      evidence to guide specific injury management approaches. An Australia-wide survey
      of professional orchestral musicians revealed that the musicians attributed
      excessively high or sudden increase in playing-load as major contributors to
      their PRMDs. Therefore, facilitating musicians to better manage these loads
      should be a cornerstone of physical therapy management. The Sound Practice
      orchestral musicians work health and safety project used formative and process
      evaluation approaches to develop evidence-informed and clinically applicable
      physical therapy interventions, ultimately resulting in favorable outcomes. After
      these methodologies were employed, the intervention studies were conducted with a
      national cohort of professional musicians including: health education, onsite
      injury management, cross-training exercise regimes, performance postural
      analysis, and music performance biomechanics feedback. The outcomes of all these
      interventions will be discussed alongside a focussed review on the existing
      literature of these management strategies. Finally, a framework for best-practice
      physical therapy management of PRMDs in musicians will be provided. 

PMID- 25071674
TI  - Learners misperceive the benefits of redundant text in multimedia learning.
AB  - Research on metacognition has consistently demonstrated that learners fail to
      endorse instructional designs that produce benefits to memory, and often prefer
      designs that actually impair comprehension. Unlike previous studies in which
      learners were only exposed to a single multimedia design, the current study used
      a within-subjects approach to examine whether exposure to both redundant text and
      non-redundant text multimedia presentations improved learners' metacognitive
      judgments about presentation styles that promote better understanding. A
      redundant text multimedia presentation containing narration paired with verbatim
      on-screen text (Redundant) was contrasted with two non-redundant text multimedia
      presentations: (1) narration paired with images and minimal text (Complementary)
      or (2) narration paired with minimal text (Sparse). Learners watched presentation
      pairs of either Redundant + Complementary, or Redundant + Sparse. Results
      demonstrate that Complementary and Sparse presentations produced highest overall
      performance on the final comprehension assessment, but the Redundant presentation
      produced highest perceived understanding and engagement ratings. These findings
      suggest that learners misperceive the benefits of redundant text, even after
      direct exposure to a non-redundant, effective presentation. 

PMID- 25071675
TI  - Temporal reward discounting in children, adolescents, and emerging adults during
      an experiential task.
AB  - The goal of this study was to examine age effects on the ability/willingness to
      wait for large rewards in a real temporal reward discounting task from childhood
      to adulthood. Therefore, a real temporal discounting (TD) task was administered
      to children aged 6-12 (n = 39), adolescents aged 13-17 (n = 28), and young adults
      aged 18-19 (n = 55). Findings indicated that the cross-sectional development of
      TD followed a quadratic pattern across age groups, with adolescents choosing more
      often than children and adults to wait for the large delayed reward, resulting in
      reward-maximization. Various interpretations of this finding were offered,
      including a focus on reward maximization despite an immature ability to exert
      self-control, and flexible self-control which was high during this task as a
      result of strong motivation to maximize financial gains. 

PMID- 25071676
TI  - Smelling phenomenal.
AB  - Qualitative-consciousness arises at the sensory level of olfactory processing and
      pervades our experience of smells to the extent that qualitative character is
      maintained whenever we are aware of undergoing an olfactory experience. Building
      upon the distinction between Access and Phenomenal Consciousness the paper offers
      a nuanced distinction between Awareness and Qualitative-consciousness that is
      applicable to olfaction in a manner that is conceptual precise and empirically
      viable. Mounting empirical research is offered substantiating the applicability
      of the distinction to olfaction and showing that olfactory qualitative
      consciousness can occur without awareness, but any olfactory state that we are
      aware of being in is always qualitative. Evidence that olfactory sensory states
      have a qualitatively character in the absence of awareness derives from research
      on mate selection, the selection of social preference for social interaction and
      acquaintances, as well as the role of olfactory deficits in causing affective
      disorders. Furthermore, the conservation of secondary processing measures of
      olfactory valence during olfactory imagery experiments provides verification that
      olfactory awareness is always qualitatively conscious-all olfactory consciousness
      smells phenomenal. 

PMID- 25071677
TI  - The measurement of consciousness: a framework for the scientific study of
      consciousness.
AB  - Scientists studying consciousness are attempting to identify correlations between
      measurements of consciousness and the physical world. Consciousness can only be
      measured through first-person reports, which raises problems about the accuracy
      of first-person reports, the possibility of non-reportable consciousness and the
      causal closure of the physical world. Many of these issues could be resolved by
      assuming that consciousness is entirely physical or functional. However, this
      would sacrifice the theory-neutrality that is a key attraction of a correlates
      based approach to the study of consciousness. This paper puts forward a different
      solution that uses a framework of definitions and assumptions to explain how
      consciousness can be measured. This addresses the problems associated with first
      person reports and avoids the issues with the causal closure of the physical
      world. This framework is compatible with most of the current theories of
      consciousness and it leads to a distinction between two types of correlates of
      consciousness. 

PMID- 25071678
TI  - iPads in early education: separating assumptions and evidence.

PMID- 25071679
TI  - In search of conceptual frameworks for relating brain activity to language
      function.

PMID- 25071680
TI  - Interval discrimination across different duration ranges with a look at spatial
      compatibility and context effects.
AB  - In the present study, a time discrimination task was used to investigate the
      effect of different contexts for intervals varying from 400 to 1600 ms. A
      potential time-space interaction was controlled, and participants used both
      manual responses (Experiments 1 and 2) and vocal responses (Experiment 3). Three
      ranges of durations were employed (short, middle and long), and within each range
      condition, three standard values were used (400, 700, and 1000 ms; 700, 1000, and
      1300 ms; and 1000, 1300, and 1600 ms). Within each range, standard intervals were
      randomized (Experiments 1 and 3) or remained constant (Experiment 2) within a
      block of trials. Our results suggest that context influences time discrimination
      performances only when the temporal range under investigation is below 1300 ms
      and the temporal intervals varied within blocks. In the case of temporal
      intervals longer than 1300 ms, participants presented a tendency to respond
      "long" independently of the procedure used. Moreover, our results suggested that
      performances in a discrimination task are mainly influenced by the fact of
      varying standard durations within blocks, and not much by the time-space
      compatibility. 

PMID- 25071682
TI  - Knowing You, Knowing Me (KYKM): an interactive game to address positive mother
      daughter communication and relationships.
AB  - This technical report describes an interactive game environment designed to bring
      mothers and their adolescent daughters together to discuss three issues that have
      previously been shown in the literature to be of concern to families, as young
      girls transition from middle childhood to the adolescent years. The game is
      called Knowing you, Knowing me or KYKM, and is used to help mothers and daughters
      discuss the following three topics: positive communication skills, relationship
      building, and managing risky behaviors in the social environment. As the game
      remains untested, its limitations and future implications of its utility are
      discussed. 

PMID- 25071681
TI  - The development of contour processing: evidence from physiology and
      psychophysics.
AB  - Object perception and pattern vision depend fundamentally upon the extraction of
      contours from the visual environment. In adulthood, contour or edge-level
      processing is supported by the Gestalt heuristics of proximity, collinearity, and
      closure. Less is known, however, about the developmental trajectory of contour
      detection and contour integration. Within the physiology of the visual system,
      long-range horizontal connections in V1 and V2 are the likely candidates for
      implementing these heuristics. While post-mortem anatomical studies of human
      infants suggest that horizontal interconnections reach maturity by the second
      year of life, psychophysical research with infants and children suggests a
      considerably more protracted development. In the present review, data from
      infancy to adulthood will be discussed in order to track the development of
      contour detection and integration. The goal of this review is thus to integrate
      the development of contour detection and integration with research regarding the
      development of underlying neural circuitry. We conclude that the ontogeny of this
      system is best characterized as a developmentally extended period of associative
      acquisition whereby horizontal connectivity becomes functional over longer and
      longer distances, thus becoming able to effectively integrate over greater spans
      of visual space. 

PMID- 25071683
TI  - Why are people with high self-control happier? The effect of trait self-control
      on happiness as mediated by regulatory focus.
AB  - BACKGROUND: While self-control has often been related to positive outcomes in
      life such as higher academic achievements and better health, recent insights
      reveal that people with high trait self-control (TSC) may even experience greater
      life satisfaction or happiness. OBJECTIVE: The current study further scrutinizes
      this potential association between TSC and happiness, and examines how regulatory
      focus, defined as the way people frame and direct their goal pursuit strategies,
      plays a role in this relationship. Accordingly, the present study examines the
      mediating role of regulatory-focus (promotion and prevention focus) on the
      relationship between TSC and happiness. METHOD: Data was collected from 545
      individuals (65.9% female, M age = 27.52 years) regarding their TSC, regulatory
      focus, and happiness. RESULTS: Mediation analyses demonstrate that TSC positively
      predicts happiness, while this effect was partially mediated by relatively more
      promotion focus and less prevention focus. CONCLUSION: RESULTS suggest that
      people with higher TSC are happier possibly because they are: (1) more promotion
      focused on acquiring positive gains thereby facilitating more approach-oriented
      behaviors, and (2) less prevention-focused on avoiding losses thereby reducing
      avoidance-oriented behaviors. These findings are relevant for topical scientific
      debates regarding the underlying mechanisms of self-control regarding initiatory
      and inhibitory behaviors.

PMID- 25071684
TI  - Are there really autonomous "unconscious" goals that drive behavior? An event
      control approach to goals and actions.

PMID- 25071686
TI  - What is the McGurk effect?

PMID- 25071685
TI  - On the use of continuous flash suppression for the study of visual processing
      outside of awareness.
AB  - The interocular suppression technique termed continuous flash suppression (CFS)
      has become an immensely popular tool for investigating visual processing outside
      of awareness. The emerging picture from studies using CFS is that extensive
      processing of a visual stimulus, including its semantic and affective content,
      occurs despite suppression from awareness of that stimulus by CFS. However, the
      current implementation of CFS in many studies examining processing outside of
      awareness has several drawbacks that may be improved upon for future studies
      using CFS. In this paper, we address some of those shortcomings, particularly
      ones that affect the assessment of unawareness during CFS, and ones to do with
      the use of "visible" conditions that are often included as a comparison to a CFS
      condition. We also discuss potential biases in stimulus processing as a result of
      spatial attention and feature-selective suppression. We suggest practical
      guidelines that minimize the effects of those limitations in using CFS to study
      visual processing outside of awareness. 

PMID- 25071687
TI  - Rethinking conformity and imitation: divergence, convergence, and social
      understanding.
AB  - Social and developmental psychologists have stressed the pervasiveness and
      strength of humans' tendencies to conform and to imitate, and social
      anthropologists have argued that these tendencies are crucial to the formation of
      cultures. Research from four domains is reviewed and elaborated to show that
      divergence is also pervasive and potent, and it is interwoven with convergence in
      a complex set of dynamics that is often unnoticed or minimized. First, classic
      research in social conformity is reinterpreted in terms of truth, trust, and
      social solidarity, revealing that dissent is its most salient feature. Second,
      recent studies of children's use of testimony to guide action reveal a
      surprisingly sophisticated balance of trust and prudence, and a concern for truth
      and charity. Third, new experiments indicate that people diverge from others even
      under conditions where conformity seems assured. Fourth, current studies of
      imitation provide strong evidence that children are both selective and faithful
      in who, what, and why they follow others. All of the evidence reviewed points
      toward children and adults as being engaged, embodied partners with others,
      motivated to learn and understand the world, others, and themselves in ways that
      go beyond goals and rules, prediction and control. Even young children act as if
      they are in a dialogical relationship with others and the world, rather than
      acting as if they are solo explorers or blind followers. Overall, the evidence
      supports the hypothesis that social understanding cannot be reduced to
      convergence or divergence, but includes ongoing activities that seek greater
      comprehensiveness and complexity in the ability to act and interact effectively,
      appropriately, and with integrity. 

PMID- 25071688
TI  - Forgiving, fast and slow: validity of the implicit association test for
      predicting differential response latencies in a transgression-recall paradigm.
AB  - This study examined the role of automaticity in forgiving a real-life offense. As
      an alternative to self-report, an Implicit Association Test (IAT) of forgiveness
      was developed. Implicit (IAT-measured) and explicit (self-reported) forgiveness
      predicted shorter response times of state forgiveness ratings. The forgiveness
      IAT was highly reliable, moderately stable over time, and demonstrated
      incremental validity. Results suggest that the newly introduced forgiveness IAT
      could advance personality research beyond what is known from self-report
      measures, further corroborating the notion of implicit forgiveness. Implications
      for personality assessment are discussed. 

PMID- 25071689
TI  - Developing a dancer wellness program employing developmental evaluation.
AB  - Wellness programs are being increasingly employed with performing artists. Given
      their aim of reducing injuries, injury tracking is commonly employed as an
      outcome measure. Evaluating the development and process of a wellness program can
      also enhance its effectiveness. Developmental evaluation offers one
      methodological framework within which to conduct such investigations. This paper
      reports on a 2-year process involving feedback from professional ballet dancers,
      management and artistic staff, and healthcare providers at a ballet company in
      order to develop a dancer screening and wellness program. Following a
      consultation phase, an initial program composed of an expanded medical team and
      annual injury prevention screen was proposed. Alongside implementation with 30
      professional ballet dancers, formal and informal feedback was sought from
      stakeholders and members across all levels of the ballet company to facilitate
      ongoing development, evaluation, and revision of the wellness program. The use of
      a process informed by developmental evaluation helped identify strengths and
      limitations within the screening process. The collective expertise of the
      assessors was used to modify the components and process of the screen to strive
      for ecological appropriateness. The process also fostered buy-in from all
      involved. Participant feedback helped refine the medical team available to the
      dancers and influenced the treatment and referral pathways via which dancers are
      able to access each member of the medical team. Furthermore, reflective
      discussions with artistic and management staff brought to light potential
      interactions between repertoire programming, fitness, and injury patterns. This
      prompted a reconsideration of how artists are trained and supported. Evaluation
      methods that focus on experiences and insight gained during program development
      stand to result in more efficient screening programs and health-promotion models
      and, ultimately, healthier performing artists. 

PMID- 25071690
TI  - How do episodic and semantic memory contribute to episodic foresight in young
      children?
AB  - Humans are able to transcend the present and mentally travel to another time,
      place, or perspective. Mentally projecting ourselves backwards (i.e., episodic
      memory) or forwards (i.e., episodic foresight) in time are crucial
      characteristics of the human memory system. Indeed, over the past few years,
      episodic memory has been argued to be involved both in our capacity to retrieve
      our personal past experiences and in our ability to imagine and foresee future
      scenarios. However, recent theory and findings suggest that semantic memory also
      plays a significant role in imagining future scenarios. We draw on Tulving's
      definition of episodic and semantic memory to provide a critical analysis of
      their role in episodic foresight tasks described in the developmental literature.
      We conclude by suggesting future directions of research that could further our
      understanding of how both episodic memory and semantic memory are intimately
      connected to episodic foresight. 

PMID- 25071692
TI  - Statistical learning under incidental versus intentional conditions.
AB  - Statistical learning (SL) studies have shown that participants are able to
      extract regularities in input they are exposed to without any instruction to do
      so. This and other findings, such as the fact that participants are often unable
      to verbalize their acquired knowledge, suggest that SL can occur implicitly or
      incidentally. Interestingly, several studies using the related paradigms of
      artificial grammar learning and serial response time tasks have shown that
      explicit instructions can aid learning under certain conditions. Within the SL
      literature, however, very few studies have contrasted incidental and intentional
      learning conditions. The aim of the present study was to investigate the effect
      of having prior knowledge of the statistical regularities in the input when
      undertaking a task of visual sequential SL. Specifically, we compared the degree
      of SL exhibited by participants who were informed (intentional group) versus
      those who were uninformed (incidental group) about the presence of embedded
      triplets within a familiarization stream. Somewhat surprisingly, our results
      revealed that there were no statistically significant differences (and only a
      small effect size) in the amount of SL exhibited between the intentional versus
      the incidental groups. We discuss the ways in which this result can be
      interpreted and suggest that short presentation times for stimuli in the
      familiarization stream in our study may have limited the opportunity for explicit
      learning. This suggestion is in line with recent research revealing a
      statistically significant difference (and a large effect size) between
      intentional versus incidental groups using a very similar visual sequential SL
      task, but with longer presentation times. Finally, we outline a number of
      directions for future research. 

PMID- 25071691
TI  - Beat-induced fluctuations in auditory cortical beta-band activity: using EEG to
      measure age-related changes.
AB  - People readily extract regularity in rhythmic auditory patterns, enabling
      prediction of the onset of the next beat. Recent magnetoencephalography (MEG)
      research suggests that such prediction is reflected by the entrainment of
      oscillatory networks in the brain to the tempo of the sequence. In particular,
      induced beta-band oscillatory activity from auditory cortex decreases after each
      beat onset and rebounds prior to the onset of the next beat across tempi in a
      predictive manner. The objective of the present study was to examine the
      development of such oscillatory activity by comparing electroencephalography
      (EEG) measures of beta-band fluctuations in 7-year-old children to adults. EEG
      was recorded while participants listened passively to isochronous tone sequences
      at three tempi (390, 585, and 780 ms for onset-to-onset interval). In adults,
      induced power in the high beta-band (20-25 Hz) decreased after each tone onset
      and rebounded prior to the onset of the next tone across tempo conditions,
      consistent with MEG findings. In children, a similar pattern was measured in the
      two slower tempo conditions, but was weaker in the fastest condition. The results
      indicate that the beta-band timing network works similarly in children, although
      there are age-related changes in consistency and the tempo range over which it
      operates. 

PMID- 25071693
TI  - To characterize contrast detection, noise should be extended, not localized.
AB  - Adding noise to a stimulus is useful to characterize visual processing. To avoid
      triggering a processing strategy shift between the processing in low and high
      noise, Allard and Cavanagh (2011) recommended using noise that is extended as a
      function of all dimensions such as space, time, frequency and orientation.
      Contrariwise, to avoid cross-channel suppression affecting contrast detection,
      Baker and Meese (2012) suggested using noise that is localized as a function of
      all dimensions, namely "0D noise," which basically consists in randomly jittering
      the target contrast (and, for blank intervals or catch trials, jittering the
      contrast of an identical zero-contrast signal). Here we argue that contrast
      thresholds in extended noise are not contaminated by noise-induced cross-channel
      suppression because contrast gains affect signal and noise by the same proportion
      leaving the signal-to-noise ratio intact. We also review empirical findings
      showing that detecting a target in 0D noise involves a different processing
      strategy than detecting in absence of noise or in extended noise. Given that
      internal noise is extended as a function of all dimensions, we therefore
      recommend using external noise that is also extended as a function of all
      dimensions when assuming that the same processing strategy operates in low and
      high noise. 

PMID- 25071694
TI  - The anxiolytic effects of resistance exercise.
AB  - Numerous studies have revealed the beneficial effects of regular exercise across
      a variety of mental health measures. Although a great deal of attention has been
      paid to the role of aerobic exercise, less is known about the role of resistance
      exercise (i.e., strength training) in mental health outcomes. Resistance exercise
      includes a broad group of procedures that evoke repeated muscle action against
      resistances above those encountered in daily life. A growing body of literature
      has identified anxiolytic effects of resistance exercise in human populations
      after both single-bout sessions and long-term training. This research has shown
      that resistance training at a low-to-moderate intensity (<70% 1 repetition
      maximum) produces the most reliable and robust decreases in anxiety. Importantly,
      anxiolytic effects have been observed across a diverse range of populations and
      dependent measures. These findings provide support for the use of resistance
      exercise in the clinical management of anxiety. 

PMID- 25071695
TI  - Network Connectivity in Epilepsy: Resting State fMRI and EEG-fMRI Contributions.
AB  - There is a growing body of evidence pointing toward large-scale networks
      underlying the core phenomena in epilepsy, from seizure generation to cognitive
      dysfunction or response to treatment. The investigation of networks in epilepsy
      has become a key concept to unlock a deeper understanding of the disease.
      Functional imaging can provide valuable information to characterize network
      dysfunction; in particular resting state fMRI (RS-fMRI), which is increasingly
      being applied to study brain networks in a number of diseases. In patients with
      epilepsy, network connectivity derived from RS-fMRI has found connectivity
      abnormalities in a number of networks; these include the epileptogenic, cognitive
      and sensory processing networks. However, in majority of these studies, the
      effect of epileptic transients in the connectivity of networks has been
      neglected. EEG-fMRI has frequently shown networks related to epileptic transients
      that in many cases are concordant with the abnormalities shown in RS studies.
      This points toward a relevant role of epileptic transients in the network
      abnormalities detected in RS-fMRI studies. In this review, we summarize the
      network abnormalities reported by these two techniques side by side, provide
      evidence of their overlapping findings, and discuss their significance in the
      context of the methodology of each technique. A number of clinically relevant
      factors that have been associated with connectivity changes are in turn
      associated with changes in the frequency of epileptic transients. These factors
      include different aspects of epilepsy ranging from treatment effects, cognitive
      processes, or transition between different alertness states (i.e., awake-sleep
      transition). For RS-fMRI to become a more effective tool to investigate
      clinically relevant aspects of epilepsy it is necessary to understand
      connectivity changes associated with epileptic transients, those associated with
      other clinically relevant factors and the interaction between them, which
      represents a gap in the current literature. We propose a framework for the
      investigation of network connectivity in patients with epilepsy that can
      integrate epileptic processes that occur across different time scales such as
      epileptic transients and disease duration and the implications of this approach
      are discussed. 

PMID- 25071696
TI  - Studies on the Q175 Knock-in Model of Huntington's Disease Using Functional
      Imaging in Awake Mice: Evidence of Olfactory Dysfunction.
AB  - Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify
      differences in brain activity between wild-type, HETzQ175, and HOMzQ175 genotypes
      in response to the odor of almond. The study was designed to see how alterations
      in the huntingtin gene in a mouse model of Huntington's disease would affect the
      perception and processing of almond odor, an evolutionarily conserved stimulus
      with high emotional and motivational valence. Moreover, the mice in this study
      were "odor naive," i.e., never having smelled almond or any nuts. Using a
      segmented, annotated MRI atlas of the mouse and computational analysis, 17 out of
      116 brain regions were identified as responding differently to almond odor across
      genotypes. These regions included the glomerulus of the olfactory bulb, forebrain
      cortex, anterior cingulate, subiculum, and dentate gyrus of the hippocampus, and
      several areas of the hypothalamus. In many cases, these regions showed a gene
      dose effect with HETzQ175 mice showing a reduction in brain activity from wild
      type that is further reduced in HOMzQ175 mice. Conspicuously absent were any
      differences in brain activity in the caudate/putamen, thalamus, CA3, and CA1 of
      the hippocampus and much of the cortex. The glomerulus of the olfactory bulb in
      HOMzQ175 mice showed a reduced change in BOLD signal intensity in response to
      almond odor as compared to the other phenotypes suggesting a deficit in olfactory
      sensitivity. 

PMID- 25071697
TI  - Microelectrode array recordings from the ventral roots in chronically implanted
      cats.
AB  - The ventral spinal roots contain the axons of spinal motoneurons and provide the
      only location in the peripheral nervous system where recorded neural activity can
      be assured to be motor rather than sensory. This study demonstrates recordings of
      single unit activity from these ventral root axons using floating microelectrode
      arrays (FMAs). Ventral root recordings were characterized by examining single
      unit yield and signal-to-noise ratios (SNR) with 32-channel FMAs implanted
      chronically in the L6 and L7 spinal roots of nine cats. Single unit recordings
      were performed for implant periods of up to 12 weeks. Motor units were identified
      based on active discharge during locomotion and inactivity under anesthesia.
      Motor unit yield and SNR were calculated for each electrode, and results were
      grouped by electrode site size, which were varied systematically between 25 and
      160 MUm to determine effects on signal quality. The unit yields and SNR did not
      differ significantly across this wide range of electrode sizes. Both SNR and
      yield decayed over time, but electrodes were able to record spikes with SNR >2 up
      to 12 weeks post-implant. These results demonstrate that it is feasible to record
      single unit activity from multiple isolated motor units with penetrating
      microelectrode arrays implanted chronically in the ventral spinal roots. This
      approach could be useful for creating a spinal nerve interface for advanced
      neural prostheses, and results of this study will be used to improve design of
      microelectrodes for chronic neural recording in the ventral spinal roots. 

PMID- 25071698
TI  - Adaptive brain shut-down counteracts neuroinflammation in the near-term ovine
      fetus.
AB  - OBJECTIVE: Repetitive umbilical cord occlusions (UCOs) in ovine fetus leading to
      severe acidemia result in adaptive shut-down of electrocortical activity
      [electrocorticogram (ECoG)] as well as systemic and brain inflammation. We
      hypothesized that the fetuses with earlier ECoG shut-down as a neuroprotective
      mechanism in response to repetitive UCOs will show less brain inflammation and,
      moreover, that chronic hypoxia will impact this relationship. METHODS: Near-term
      fetal sheep were chronically instrumented with ECoG leads, vascular catheters,
      and a cord occluder and then underwent repetitive UCOs for up to 4 h or until
      fetal arterial pH was <7.00. Eight animals, hypoxic prior to the UCOs (SaO2
      <55%), were allowed to recover 24 h post insult, while 14 animals, 5 of whom also
      were chronically hypoxic, were allowed to recover 48 h post insult, after which
      brains were perfusion-fixed. Time of ECoG shut-down and corresponding pH were
      noted, as well as time to then reach pH <7.00 (DeltaT). Microglia (MG) were
      counted as a measure of inflammation in gray matter layers 4-6 (GM4-6) where most
      ECoG activity is generated. RESULTS are reported as mean +/- SEM for p < 0.05.
      RESULTS: Repetitive UCOs resulted in worsening acidosis over 3-4 h with arterial
      pH decreasing to 6.97 +/- 0.02 all UCO groups' animals, recovering to baseline by
      24 h. ECoG shut-down occurred 52 +/- 7 min before reaching pH <7.00 at pH 7.23 +/
      0.02 across the animal groups. MG counts were inversely correlated to DeltaT in
      24 h recovery animals (R = -0.84), as expected. This was not the case in normoxic
      48 h recovery animals, and, surprisingly, in hypoxic 48 h recovery animals, this
      relationship was reversed (R = 0.90). CONCLUSION: Adaptive brain shut-down during
      labor-like worsening acidemia counteracts neuroinflammation in a hypoxia- and
      time-dependent manner.

PMID- 25071700
TI  - Keep an eye out for myasthenia gravis patients with an eye out.
AB  - Eye trauma and blindness are common in the United States, with an incidence of
      over 2 million cases/year and 25 million blind adults, respectively. However,
      literature is surprisingly scarce on the potential confounding effect of eye
      trauma or blindness on the diagnosis of myasthenia gravis (MG), an autoimmune
      neuromuscular disease in which fluctuating ocular symptoms are the most
      distinguishing feature. We present the case of a 75-year-old man with eye
      enucleation referred for electrodiagnostic evaluation of the right upper limb
      after an accidental fall. Neurological examination showed proximal muscle
      weakness, but MG was not initially considered because the patient lacked the
      classic ocular symptoms of MG. The delay in diagnosis resulted in worsening of
      systemic MG symptoms, although in other patients it may have precipitated MG
      crisis or possibly death. Greater awareness that eye trauma or blindness can
      prevent expression of ocular symptoms in neuromuscular disorders is needed to
      avoid morbidity associated with an erroneous or delayed diagnosis. 

PMID- 25071699
TI  - Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure
      Frequency in Two Chronic Models of Temporal Lobe Epilepsy.
AB  - Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human
      temporal lobe epilepsy (TLE) but the distribution and severity of structural
      lesions between these two models may differ. Magnetic resonance imaging (MRI)
      studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation
      time and volume, but simultaneous comparative results have not been reported yet.
      The aim of this study was to compare the MRI T2HP and volume with histological
      data and frequency of seizures in both models. KA- and PILO-treated rats were
      imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the
      number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS)
      frequency over the 9 months following status epilepticus (SE). Compared to
      controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal
      volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3
      months post SE. In contrast, hippocampal volume was unchanged in PILO-treated
      animals despite detectable increased T2HP and cell loss in granule cell layer,
      CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable
      with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3
      cells was smaller than age-matched CTL group. In contrast, PILO group had MRI
      volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells.
      In this group, T2HP signal was unaltered at 6 or 9 months after status.
      Reductions in the number of cells were not progressive in both models. Notably,
      the SRS frequency was higher in PILO than in the KA model. The volumetry data
      correlated well with tissue damage in the epileptic brain, suggesting that MRI
      may be useful for tracking longitudinal hippocampal changes, allowing the
      assessment of individual variability and disease progression. Our results
      indicate that the temporal changes in hippocampal morphology are distinct for
      both models of TLE and that these are not significantly correlated to the
      frequency of SRS. 

PMID- 25071701
TI  - Penetrating brain injury after suicide attempt with speargun: case study and
      review of literature.
AB  - Penetrating cranial injury by mechanisms other than gunshots are exceedingly
      rare, and so strategies and guidelines for the management of PBI are largely
      informed by data from higher-velocity penetrating injuries. Here, we present a
      case of penetrating brain injury by the low-velocity mechanism of a harpoon from
      an underwater fishing speargun in an attempted suicide by a 56-year-old Caucasian
      male. The case raised a number of interesting points in management of low
      velocity penetrating brain injury (LVPBI), including benefit in delaying foreign
      body removal to allow for tamponade; the importance of history-taking in
      establishing the social/legal significance of the events surrounding the injury;
      the use of cerebral angiogram in all cases of PBI; advantages of using dual
      energy CT to reduce artifact when available; and antibiotic prophylaxis in the
      context of idiosyncratic histories of usage of penetrating objects before coming
      in contact with the intracranial environment. We present here the management of
      the case in full along with an extended discussion and review of existing
      literature regarding key points in management of LVPBI vs. higher-velocity forms
      of intracranial injury. 

PMID- 25071703
TI  - Circadian fatigue or unrecognized restless legs syndrome? The post-polio syndrome
      model.

PMID- 25071702
TI  - Imaging of cerebral blood flow in patients with severe traumatic brain injury in
      the neurointensive care.
AB  - Ischemia is a common and deleterious secondary injury following traumatic brain
      injury (TBI). A great challenge for the treatment of TBI patients in the
      neurointensive care unit (NICU) is to detect early signs of ischemia in order to
      prevent further advancement and deterioration of the brain tissue. Today, several
      imaging techniques are available to monitor cerebral blood flow (CBF) in the
      injured brain such as positron emission tomography (PET), single-photon emission
      computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted
      magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging
      technique would enable continuous non-invasive measurement of blood flow and
      metabolism across the whole brain. Unfortunately, no current imaging method meets
      all these criteria. These techniques offer snapshots of the CBF. MRI may also
      provide some information about the metabolic state of the brain. PET provides
      images with high resolution and quantitative measurements of CBF and metabolism;
      however, it is a complex and costly method limited to few TBI centers. All of
      these methods except mobile Xenon-CT require transfer of TBI patients to the
      radiological department. Mobile Xenon-CT emerges as a feasible technique to
      monitor CBF in the NICU, with lower risk of adverse effects. Promising results
      have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This
      review covers available imaging methods used to monitor CBF in patients with
      severe TBI. 

PMID- 25071704
TI  - The Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale: An Assessment
      of Reliability and Validity.
AB  - The IBB scale is a recently developed forelimb scale for the assessment of fine
      control of the forelimb and digits after cervical spinal cord injury [SCI; (1)].
      The present paper describes the assessment of inter-rater reliability and face,
      concurrent and construct validity of this scale following SCI. It demonstrates
      that the IBB is a reliable and valid scale that is sensitive to severity of SCI
      and to recovery over time. In addition, the IBB correlates with other outcome
      measures and is highly predictive of biological measures of tissue pathology.
      Multivariate analysis using principal component analysis (PCA) demonstrates that
      the IBB is highly predictive of the syndromic outcome after SCI (2), and is among
      the best predictors of bio-behavioral function, based on strong construct
      validity. Altogether, the data suggest that the IBB, especially in concert with
      other measures, is a reliable and valid tool for assessing neurological deficits
      in fine motor control of the distal forelimb, and represents a powerful addition
      to multivariate outcome batteries aimed at documenting recovery of function after
      cervical SCI in rats. 

PMID- 25071705
TI  - Upper limb function and cortical organization in youth with unilateral cerebral
      palsy.
AB  - AIM: To explore the relationship between motor cortical and descending motor
      pathway reorganization, lesion type, and upper limb function in youth with
      unilateral cerebral palsy (CP). METHODS: Twenty participants with unilateral CP
      (mean age 15 +/- 3 years; 11 males) completed a range of upper limb functional
      measures. Structural MRI, diffusion-weighted, and functional MRI were conducted
      to determine type and extent of brain lesion, descending white matter integrity,
      and whole-brain activity during affected hand use. Single pulse transcranial
      magnetic stimulation (TMS) (n = 12) was used to examine functional integrity of
      the corticospinal pathway as well as primary motor cortex intracortical and
      interhemispheric inhibition from motor-evoked potentials and silent periods.
      RESULTS: Fractional anisotropy measures within the posterior limb of the internal
      capsule were a predictor of upper limb function (R (2) = 0.41, F = 11.3, p =
      0.004). Participants with periventricular lesions tended to have better upper
      limb function [F(2, 17) = 42.48, p < 0.0001]. Five participants with evidence of
      cortical reorganization and functional ipsilateral projections to their affected
      hand had worse upper limb function. Deficits in intracortical and
      interhemispheric inhibitory mechanisms were found in participants with worse
      upper limb function (Melbourne Assessment of Unilateral Upper Limb Function: Mann
      Whitney p = 0.02). CONCLUSION: Neuroimaging and TMS can provide useful
      information related to hand function of individuals with unilateral CP and may
      have potential to assist as a predictive tool and/or guide rehabilitation.

PMID- 25071706
TI  - Sleep disturbances and autonomic dysfunction in patients with postural
      orthostatic tachycardia syndrome.
AB  - Many patients with postural tachycardia syndrome (PoTS) suffer from fatigue,
      daytime sleepiness, and sleeping disturbances. The objective of this study was to
      compare subjective and objective sleep quality of PoTS patients with a group of
      healthy controls. All patients completed a Pittsburgh Sleep Quality Index
      questionnaire and the Epworth Sleepiness Scale. The patients sleep architecture,
      heart rate, and heart rate variability (HRV) measurements were taken during one
      night at the sleep laboratorium. All data was collected at the Sleep Unit, at
      Helios Klinikum Wuppertal. Thirty-eight patients diagnosed with PoTS were
      compared to 31 healthy controls, matched in age and gender. Patients with PoTS
      reached significantly higher scores in sleep questionnaires, which means that
      they were more sleepy and had a lower sleep quality. Polysomnography showed a
      significantly higher proportion of stage 2 sleep. The results of HRV analysis in
      different sleep stages confirmed changes in autonomic activity in both groups.
      PoTS patients, however, showed a diminished variability of the low-frequency (LF)
      band, high-frequency (HF) band, and LF/HF ratio in different sleep stages. It can
      therefore be gathered that PoTS could be considered as potential differential
      diagnosis for sleep disturbances since PoTS patients had a subjective diminished
      sleep quality, reached higher levels of daytime sleepiness, and showed a higher
      proportion of stage 2 sleep. PoTS patients showed furthermore a reduction of
      LF/HF ratio variability in different sleep stages. 

PMID- 25071707
TI  - Thrombotic processes in multiple sclerosis as manifestation of innate immune
      activation.

PMID- 25071708
TI  - Thrombophilic disorders in migraine.

PMID- 25071709
TI  - Translational Preclinical Research may Lead to Improved Medical Management of Non
      Arteritic Anterior Ischemic Optic Neuropathy.

PMID- 25071710
TI  - Natural history of intracranial atherosclerotic disease.
AB  - Intracranial atherosclerotic disease was very common among stroke patients of
      Asians, Blacks, and Hispanics ancestry. Furthermore, stroke patients with
      intracranial atherosclerosis (ICAS) have higher recurrence rate of cerebral
      ischemia and death than those without ICAS. However, the natural history of
      intracranial atherosclerotic disease is still in controversy. Most of the studies
      were retrospective and randomized controlled trial of drugs. This review
      summarized the prognosis of symptomatic and asymptomatic intracranial
      atherosclerotic disease in order to guide clinical decision-making and further
      clinical research. 

PMID- 25071711
TI  - Combining non-pharmacological treatments with pharmacotherapies for neurological
      disorders: a unique interface of the brain, drug-device, and intellectual
      property.
AB  - Mobile medical applications (mHealth), music, and video games are being developed
      and tested for their ability to improve pharmacotherapy outcomes and medication
      adherence. Pleiotropic mechanism of music and gamification engages an intrinsic
      motivation and the brain reward system, supporting therapies in patients with
      neurological disorders, including neuropathic pain, depression, anxiety, or
      neurodegenerative disorders. Based on accumulating results from clinical trials,
      an innovative combination treatment of epilepsy seizures, comorbidities, and the
      medication non-adherence can be designed, consisting of antiepileptic drugs and
      disease self-management software delivering clinically beneficial music. Since
      creative elements and art expressed in games, music, and software are
      copyrighted, therefore clinical and regulatory challenges in developing
      copyrighted, drug-device therapies may be offset by a value proposition of the
      exclusivity due to the patent-independent protection, which can last for over 70
      years. Taken together, development of copyrighted non-pharmacological treatments
      (e-therapies), and their combinations with pharmacotherapies, offer incentives to
      chronically ill patients and outcome-driven health care industries. 

PMID- 25071712
TI  - Specific resting-state brain networks in mesial temporal lobe epilepsy.
AB  - We studied with functional magnetic resonance imaging (fMRI) differences in
      resting-state networks between patients with mesial temporal lobe epilepsy (MTLE)
      and healthy subjects. To avoid any a priori hypothesis, we use a data-driven
      analysis assessing differences between groups independently of structures
      involved. Shared and specific independent component analysis (SSICA) is an
      exploratory method based on independent component analysis, which performs
      between-group network comparison. It extracts and classifies components
      (networks) in those common between groups and those specific to one group.
      Resting fMRI data were collected from 10 healthy subjects and 10 MTLE patients.
      SSICA was applied multiple times with altered initializations and different
      numbers of specific components. This resulted in many components specific to
      patients and to controls. Spatial clustering identified the reliable resting
      state networks among all specific components in each group. For each reliable
      specific network, power spectrum analysis was performed on reconstructed time
      series to estimate connectivity in each group and differences between groups. Two
      reliable networks, corresponding to statistically significant clusters robustly
      detected with clustering were labeled as specific to MTLE and one as specific to
      the control group. The most reliable MTLE network included hippocampus and
      amygdala bilaterally. The other MTLE network included the postcentral gyri and
      temporal poles. The control-specific network included bilateral precuneus,
      anterior cingulate, thalamus, and parahippocampal gyrus. Results indicated that
      the two MTLE networks show increased connectivity in patients, whereas the
      control-specific network shows decreased connectivity in patients. Our findings
      complement results from seed-based connectivity analysis (1). The pattern of
      changes in connectivity between mesial temporal lobe structures and other areas
      may help us understand the cognitive impairments often reported in patients with
      MTLE. 

PMID- 25071713
TI  - Blast-induced neurotrauma models and their requirements.

PMID- 25071714
TI  - Intracranial Angioplasty and Stenting before and after SAMMPRIS: "From Simple to
      Complex Strategy - The Chinese Experience".
AB  - Intracranial atherosclerotic disease (ICAD) accounts for 33-50% of all ischemic
      strokes in the Asian population (1) and represents an important public health
      issue in China. The results of the SAMMPRIS trial alarmed most experienced
      interventionalists in China for two reasons. Firstly, the high complication rate
      in the stenting arm (20% the first year) was higher than expected. Secondly, the
      recurrent stroke rate in the aggressive medical treatment arm at 12.2% during the
      first year was unacceptably high, not to mention the fact that such tight
      vascular risk factor control is difficult to achieve for many patients in real
      life clinical experience, at least in China. The experience of treating ICAD in
      China, gained over the last two decades, is very rich and promising. We intend to
      highlight these past experiences and address future trials and trends in China.
      We will also address our criticism of the SAMMPRIS trial design in order to
      better design a future trial. 

PMID- 25071715
TI  - Recent advances and future challenges in the genetics of multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common auto-inflammatory disease of the
      central nervous system, affecting more than 2 million individuals worldwide. It
      is a genetically complex disease, in which a substantial part of a person's
      liability to develop MS is caused by a combination of multiple genetic and non
      genetic (e.g., environmental) risk factors. Increasing this complexity, many of
      the involved risk factors likely interact in an intricate and hitherto ill
      defined fashion. Despite these complexities, and owing greatly to the advent and
      application of large-scale genome-wide association studies, our understanding of
      the genetic factors underlying MS etiology has begun to gain unprecedented
      momentum. In this perspective, I will summarize some recent advances and outline
      future challenges in MS genetics research. 

PMID- 25071716
TI  - Chromium-Insulin Reduces Insulin Clearance and Enhances Insulin Signaling by
      Suppressing Hepatic Insulin-Degrading Enzyme and Proteasome Protein Expression in
      KKAy Mice.
AB  - JDS-chromium-insulin (CRI)-003 is a novel form of insulin that has been directly
      conjugated with chromium (Cr) instead of zinc. Our hypothesis was that CRI
      enhances insulin's effects by altering insulin-degrading enzyme (IDE) and
      proteasome enzymes. To test this hypothesis, we measured hepatic IDE content and
      proteasome parameters in a diabetic animal model. Male KKAy mice were randomly
      divided into three groups (n = 8/group); Sham (saline), human regular insulin
      (Reg-In), and chromium conjugated human insulin (CRI), respectively.
      Interventions were initiated at doses of 2 U insulin/kg body weight daily for 8
      weeks. Plasma glucose and insulin were measured. Hepatic IDE, proteasome, and
      insulin signaling proteins were determined by western blotting. Insulin tolerance
      tests at week 7 showed that both insulin treatments significantly reduced glucose
      concentrations and increased insulin levels compared with the Sham group, CRI
      significantly reduced glucose at 4 and 6 h relative to Reg-In (P < 0.05),
      suggesting the effects of CRI on reducing glucose last longer than Reg-In. CRI
      treatment significantly increased hepatic IRS-1 and Akt1 and reduced IDE, 20S as
      well as 19S protein abundance (P < 0.01, P < 0.05, and P < 0.001, respectively),
      but Reg-In only significantly increased Akt1 (P < 0.05). Similar results were
      also observed in Reg-In- and CRI-treated HepG2 cells. This study, for the first
      time, demonstrates that CRI reduces plasma insulin clearance by inhibition of
      hepatic IDE protein expression and enhances insulin signaling as well as prevents
      degradation of IRS-1 and IRS-2 by suppressing ubiquitin-proteasome pathway in
      diabetic mice. 

PMID- 25071717
TI  - Context modulates outcome of perinatal glucocorticoid action in the brain.
AB  - Prematurely born infants may be at risk, because of inadequate maturation of
      tissues. If there are signs of preterm birth, it has become common practice
      therefore to treat either antenatally the mother or postnatally the infant with
      glucocorticoids to accelerate tissue development, particularly of the lung.
      However, this life-saving early glucocorticoid treatment was found to increase
      the risk of adverse outcome in later life. In one animal study, the authors
      reported a 25% shorter lifespan of rats treated as newborns with the synthetic
      glucocorticoid dexamethasone, but so far this finding has not been replicated.
      After a brief clinical introduction, we discuss studies in rodents designed to
      examine how perinatal glucocorticoid action affects the developing brain. It
      appears that the perinatal action of the glucocorticoid depends on the context
      and the timing as well as the type of administered steroid. The type of steroid
      is important because the endogenous glucocorticoids cortisol and corticosterone
      bind to two distinct receptor populations, i.e., mineralocorticoid and
      glucocorticoid receptors (GR), while synthetic glucocorticoids predominantly bind
      to the GR. In addition, if given antenatally hydrocortisone is inactivated in the
      placenta by 11beta-HSD type 2, and dexamethasone is not. With respect to timing,
      the outcome of glucocorticoid effects is different in early vs. late phases of
      brain development. The context refers to the environmental input that can affect
      the susceptibility to glucocorticoid action in the newborn rodent brain; early
      handling of pups and maternal care obliterate effects of post-natal dexamethasone
      treatment. Context also refers to coping with environmental conditions in later
      life, for which the individual may have been programed epigenetically by early
      life experience. This knowledge of determinants affecting the outcome of
      perinatal glucocorticoid exposure may have clinical implications for the
      treatment of prematurely born infants. 

PMID- 25071720
TI  - Beyond the circulating Renin-Angiotensin aldosterone system.

PMID- 25071719
TI  - Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence
      Urinary Cortisol Levels in Adult Offspring.
AB  - BACKGROUND: Parental traumatization has been associated with increased risk for
      the expression of psychopathology in offspring, and maternal posttraumatic stress
      disorder (PTSD) appears to increase the risk for the development of offspring
      PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were
      evaluated for their association with offspring ambient cortisol and PTSD
      associated symptom expression. METHOD: Ninety-five Holocaust offspring and Jewish
      comparison subjects received diagnostic and psychological evaluations, and 24 h
      urinary cortisol was assayed by RIA. Offspring completed the parental PTSD
      questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was
      identified as having occurred in childhood, adolescence, or adulthood and
      examined in relation to offspring psychobiology. RESULTS: Urinary cortisol levels
      did not differ for Holocaust offspring and comparison subjects but differed
      significantly in offspring based on maternal age of exposure and maternal PTSD
      status. Increased maternal age of exposure and maternal PTSD were each associated
      with lower urinary cortisol in offspring, but did not exhibit a significant
      interaction. In addition, offspring PTSD-associated symptom severity increased
      with maternal age at exposure and PTSD diagnosis. A regression analysis of
      correlates of offspring cortisol indicated that both maternal age of exposure and
      maternal PTSD were significant predictors of lower offspring urinary cortisol,
      whereas childhood adversity and offspring PTSD symptoms were not. CONCLUSION:
      Offspring low cortisol and PTSD-associated symptom expression are related to
      maternal age of exposure, with the greatest effects associated with increased age
      at exposure. These effects are relatively independent of the negative
      consequences of being raised by a trauma survivor. These observations highlight
      the importance of maternal age of exposure in determining a psychobiology in
      offspring that is consistent with increased risk for stress-related pathology.

PMID- 25071721
TI  - Vale Neil McKern - Australian Insulin Receptor Scientist.

PMID- 25071718
TI  - Clinical concepts on thyroid emergencies.
AB  - OBJECTIVE: Thyroid-related emergencies are caused by overt dysfunction of the
      gland which are so severe that require admission to intensive care units (ICU)
      frequently. Nonetheless, in the ICU setting, it is crucial to differentiate
      patients with non-thyroidal illness and alterations in thyroid function tests
      from those with intrinsic thyroid disease. This review presents and discusses the
      main etiopathogenetical and clinical aspects of hypothyroid coma (HC) and
      thyrotoxic storm (TS), including therapeutic strategy flow-charts. Furthermore, a
      special chapter is dedicated to the approach to massive goiter, which represents
      a surgical thyroid emergency. DATA SOURCE: We searched the electronic MEDLINE
      database on September 2013. Data Selection and Data Extraction: Reviews, original
      articles, and case reports on "myxedematous coma," "HC," "thyroid storm," "TS,"
      "massive goiter," "huge goiter," "prevalence," "etiology," "diagnosis,"
      "therapy," and "prognosis" were selected. DATA SYNTHESIS AND CONCLUSION: Severe
      excess or defect of thyroid hormone is rare conditions, which jeopardize the life
      of patients in most cases. Both HC and TS are triggered by precipitating factors,
      which occur in patients with severe hypothyroidism or thyrotoxicosis,
      respectively. The pillars of HC therapy are high-dose l-thyroxine and/or tri
      iodothyroinine; i.v. glucocorticoids; treatment of hydro-electrolyte imbalance
      (mainly, hyponatraemia); treatment of hypothermia; often, endotracheal intubation
      and assisted mechanic ventilation are needed. Therapy of TS is based on beta
      blockers, thyrostatics, and i.v. glucocorticoids; eventually, high-dose of iodide
      compounds or lithium carbonate may be of benefit. Surgery represents the gold
      standard treatment in patients with euthyroid massive nodular goiter, although
      new techniques - e.g., percutaneous laser ablation - are helpful in subjects at
      high surgical risk or refusing operation.

PMID- 25071723
TI  - FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases.
AB  - Fibroblast growth factor (FGF) family members are mostly secreted as signaling
      proteins with diverse functions in development and metabolism. FGF21 is a unique
      FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by
      different kinds of stress and acts though FGF receptor 1c with beta-Klotho as a
      cofactor in an endocrine or, in parts, autocrine/paracrine manner. Hepatic FGF21
      directly acts on white adipocytes to inhibit lipolysis and acts through the brain
      to increase systemic glucocorticoid levels and suppress physical activity in
      response to starvation. It also protects against dioxin toxicity. Adipocytic
      FGF21 induces the browning of white adipose tissue (WAT) and activates brown
      adipocytes in response to cold exposure. It also acts as an upstream effector of
      adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced
      obesity and insulin resistance, induces the browning of WAT, and protects against
      cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with
      metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings
      indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in
      metabolism, injury protection, and diseases. 

PMID- 25071722
TI  - The Endocrine Milieu and CD4 T-Lymphocyte Polarization during Pregnancy.
AB  - Acceptance of the fetal semi-allograft by the mother's immune system has become
      the focus of intensive research. CD4+ T cells are important actors in the
      establishment of pregnancy. Th1/Th2 paradigm has been expanded to include CD4+
      regulatory T (Treg) and T helper 17 (Th17) cells. Pregnancy hormones exert very
      significant modulatory properties on the maternal immune system. In this review,
      we describe mechanisms by which the endocrine milieu modulates CD4 T cell
      polarization during pregnancy. We first focused on Treg and Th17 cells and on
      their importance for pregnancy. Secondly, we review the effects of pregnancy
      hormones [progesterone (P4) and estradiol (E2)] on immune cells previously
      described, with a particular attention to human chorionic gonadotropin (hCG). The
      importance of Treg cells for pregnancy is evidenced. They are recruited before
      implantation and are essential for pregnancy maintenance. Decreased number or
      less efficient Treg cells are implicated in fertility disorders. As for Th17
      cells, the few available studies suggest that they have a negative impact on
      fertility. Th17 frequency is increased in infertile patients. With the
      combination of its pro-effects on Th2 and Treg cells and anti-effects on Th1 and
      Th17 cells, P4 contributes to establishment of a favorable environment for
      pregnancy. E2 effects are more dependent on the context but it seems that E2
      promotes Treg and Th2 cells while it inhibits Th1 cells. hCG positively
      influences activities of Treg and uterine natural killer cells. This embryo
      signal is an essential actor for the success of pregnancy, both as the endocrine
      factor regulating P4 secretion by the ovarian corpus luteum, but also as a
      paracrine agent during implantation as well as an angiogenic and immunologic
      mediator during the course of gestation. Luteinizing hormone (LH) immune
      properties begin to be studied but its positive impact on Treg cells suggests
      that LH could be a considerable immunomodulator in the mouse. 

PMID- 25071724
TI  - Reproduction, smell, and neurodevelopmental disorders: genetic defects in
      different hypogonadotropic hypogonadal syndromes.
AB  - The neuroendocrine control of reproduction in mammals is governed by a neural
      hypothalamic network of nearly 1500 gonadotropin-releasing hormone (GnRH)
      secreting neurons that modulate the activity of the reproductive axis across
      life. Congenital hypogonadotropic hypogonadism (HH) is a clinical syndrome that
      is characterized by partial or complete pubertal failure. HH may result from
      inadequate hypothalamic GnRH axis activation, or a failure of pituitary
      gonadotropin secretion/effects. In man, several genes that participate in
      olfactory and GnRH neuronal migration are thought to interact during the
      embryonic life. A growing number of mutations in different genes are responsible
      for congenital HH. Based on the presence or absence of olfaction dysfunction, HH
      is divided in two syndromes: HH with olfactory alterations [Kallmann syndrome
      (KS)] and idiopathic hypogonadotropic hypogonadism (IHH) with normal smell
      (normosmic IHH). KS is a heterogeneous disorder affecting 1 in 5000 males, with a
      three to fivefold of males over females. KS is associated with mutations in KAL1,
      FGFR1/FGF8, FGF17, IL17RD, PROK2/PROKR2, NELF, CHD7, HS6ST1, FLRT3, SPRY4, DUSP6,
      SEMA3A, NELF, and WDR11 genes that are related to defects in neuronal migration.
      These reproductive and olfactory deficits include a variable non-reproductive
      phenotype, including sensorineural deafness, coloboma, bimanual synkinesis,
      craniofacial abnormalities, and/or renal agenesis. Interestingly, defects in
      PROKR2, FGFR1, FGF8, CHD7, DUSP6, and WDR11 genes are also associated with
      normosmic IHH, whereas mutations in KISS1/KISSR, TAC3/TACR3, GNRH1/GNRHR,
      LEP/LEPR, HESX1, FSHB, and LHB are only present in patients with normosmic IHH.
      In this paper, we summarize the reproductive, neurodevelopmental, and genetic
      aspects of HH in human pathology. 

PMID- 25071726
TI  - Regulation of Energy Homeostasis via GPR120.
AB  - Free fatty acids (FFAs) are fundamental units of key nutrients. FFAs exert
      various biological functions, depending on the chain length and degree of
      desaturation. Recent studies have shown that several FFAs act as ligands of G
      protein-coupled receptors (GPCRs), activate intracellular signaling and exert
      physiological functions via these GPCRs. GPR120 (also known as free fatty acid
      receptor 4) is activated by unsaturated medium- to long-chain FFAs and has a
      critical role in various physiological homeostasis mechanisms such as incretin
      hormone secretion, food preference, anti-inflammation, and adipogenesis. Recent
      studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat
      in white adipose tissue and regulates the whole body energy homeostasis in both
      humans and rodents. Genetic study in human identified the loss-of-functional
      mutation of GPR120 associated with obesity and insulin resistance. In addition,
      dysfunction of GPR120 has been linked as a novel risk factor for diet-induced
      obesity. This review aims to provide evidence from the recent development in
      physiological function of GPR120 and discusses its functional roles in the
      regulation of energy homeostasis and its potential as drug targets. 

PMID- 25071725
TI  - Insulin as a Bridge between Type 2 Diabetes and Alzheimer Disease - How Anti
      Diabetics Could be a Solution for Dementia.
AB  - Type 2 diabetes (T2D) and Alzheimer disease (AD) are two major health issues
      nowadays. T2D is an ever increasing epidemic, affecting millions of elderly
      people worldwide, with major repercussions in the patients' daily life. This is
      mostly due to its chronic complications that may affect brain and constitutes a
      risk factor for AD. T2D principal hallmark is insulin resistance which also
      occurs in AD, rendering both pathologies more than mere unrelated diseases. This
      hypothesis has been reinforced in the recent years, with a high number of studies
      highlighting the existence of several common molecular links. As such, it is not
      surprising that AD has been considered as the "type 3 diabetes" or a "brain
      specific T2D," supporting the idea that a beneficial therapeutic strategy against
      T2D might be also beneficial against AD. Herewith, we aim to review some of the
      recent developments on the common features between T2D and AD, namely on insulin
      signaling and its participation in the regulation of amyloid beta (Abeta) plaque
      and neurofibrillary tangle formation (the two major neuropathological hallmarks
      of AD). We also critically analyze the promising field that some anti-T2D drugs
      may protect against dementia and AD, with a special emphasis on the novel
      incretin/glucagon-like peptide-1 receptor agonists. 

PMID- 25071727
TI  - Clinical relevance of local Renin Angiotensin systems.

PMID- 25071728
TI  - Antibiotics promote aggregation within aquatic bacterial communities.
AB  - The release of antibiotics (AB) into the environment poses several threats for
      human health due to potential development of AB-resistant natural bacteria. Even
      though the use of low-dose antibiotics has been promoted in health care and
      farming, significant amounts of AB are observed in aquatic environments.
      Knowledge on the impact of AB on natural bacterial communities is missing both in
      terms of spread and evolution of resistance mechanisms, and of modifications of
      community composition and productivity. New approaches are required to study the
      response of microbial communities rather than individual resistance genes. In
      this study a chemostat-based experiment with 4 coexisting bacterial strains has
      been performed to mimicking the response of a freshwater bacterial community to
      the presence of antibiotics in low and high doses. Bacterial abundance rapidly
      decreased by 75% in the presence of AB, independently of their concentration, and
      remained constant until the end of the experiment. The bacterial community was
      mainly dominated by Aeromonas hydrophila and Brevundimonas intermedia while the
      other two strains, Micrococcus luteus and Rhodococcus sp. never exceed 10%.
      Interestingly, the bacterial strains, which were isolated at the end of the
      experiment, were not AB-resistant, while reassembled communities composed of the
      4 strains, isolated from treatments under AB stress, significantly raised their
      performance (growth rate, abundance) in the presence of AB compared to the
      communities reassembled with strains isolated from the treatment without AB. By
      investigating the phenotypic adaptations of the communities subjected to the
      different treatments, we found that the presence of AB significantly increased co
      aggregation by 5-6 fold. These results represent the first observation of co
      aggregation as a successful strategy of AB resistance based on phenotype in
      aquatic bacterial communities, and can represent a fundamental step in the
      understanding of the effects of AB in aquatic ecosystems. 

PMID- 25071729
TI  - Variations in the identity and complexity of endosymbiont combinations in
      whitefly hosts.
AB  - The target of natural selection is suggested to be the holobiont - the organism
      together with its associated symbiotic microorganisms. The well-defined
      endosymbiotic communities of insects make them a useful model for exploring the
      role of symbiotic interactions in shaping the functional repertoire of plants and
      animals. Here, we studied the variations in the symbiotic communities of the
      sweet potato whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) by compiling a
      dataset of over 2000 individuals derived from several independent screenings. The
      secondary endosymbionts harbored by each individual were clustered into entities
      termed Facultative Endosymbiont Combinations (FECs), each representing a natural
      assemblage of co-occurring bacterial genera. The association of FECs with
      whitefly individuals stratified the otherwise homogeneous population into
      holobiont units. We both identified bacterial assemblages that are specific to
      whitefly groups sharing unique genetic backgrounds, and characterized the FEC
      variations within these groups. The analysis revealed that FEC complexity is
      positively correlated with both distance from the equator and specificity of the
      genetic clade of the host insect. These findings highlight the importance of
      symbiotic combinations in shaping the distribution patterns of B. tabaci and
      possibly other insect species. 

PMID- 25071730
TI  - Association of antibodies to Plasmodium falciparum reticulocyte binding protein
      homolog 5 with protection from clinical malaria.
AB  - Emerging evidence suggests that antibodies against merozoite proteins involved in
      Plasmodium falciparum invasion into the red blood cell (RBC) play an important
      role in clinical immunity to malaria. The protein family of parasite antigens
      known as P. falciparum reticulocyte binding protein-like homolog (PfRh) is
      required for RBC invasion. PfRh5 is the only member within the PfRh family that
      cannot be genetically deleted, suggesting it plays an essential role in parasite
      survival. This antigen forms a complex with the cysteine-rich P. falciparum Rh5
      interacting protein (PfRipr), on the merozoite surface during RBC invasion. The
      PfRh5 ectodomain sequence and a C-terminal fragment of PfRipr were cloned and
      expressed in Escherichia coli and baculovirus-infected cells, respectively.
      Immunization of rabbits with these recombinant proteins induced antibodies able
      to inhibit growth of various P. falciparum strains. Antibody responses to these
      proteins were investigated in a treatment-re-infection study conducted in an
      endemic area of Papua New Guinea (PNG) to determine their contribution to
      naturally acquired immunity. Antibody titers to PfRh5 but not PfRipr showed
      strong association with protection against P. falciparum clinical episodes. When
      associations with time-to-first infection were analyzed, high antibody levels
      against PfRh5 were also found to be associated with protection from high-density
      infections but not from re-infection. Together these results indicate that PfRh5
      is an important target of protective immunity and constitutes a promising vaccine
      candidate. 

PMID- 25071731
TI  - Inhibition of microbial sulfate reduction in a flow-through column system by
      (per)chlorate treatment.
AB  - Microbial sulfate reduction is a primary cause of oil reservoir souring. Here we
      show that amendment with chlorate or perchlorate [collectively (per)chlorate]
      potentially resolves this issue. Triplicate packed columns inoculated with marine
      sediment were flushed with coastal water amended with yeast extract and one of
      nitrate, chlorate, or perchlorate. Results showed that although sulfide
      production was dramatically reduced by all treatments, effluent sulfide was
      observed in the nitrate (10 mM) treatment after an initial inhibition period. In
      contrast, no effluent sulfide was observed with (per)chlorate (10 mM). Microbial
      community analyses indicated temporal community shifts and phylogenetic
      clustering by treatment. Nitrate addition stimulated Xanthomonadaceae and
      Rhizobiaceae growth, supporting their role in nitrate metabolism. (Per)chlorate
      showed distinct effects on microbial community structure compared with nitrate
      and resulted in a general suppression of the community relative to the untreated
      control combined with a significant decrease in sulfate reducing species
      abundance indicating specific toxicity. Furthermore, chlorate stimulated
      Pseudomonadaceae and Pseudoalteromonadaceae, members of which are known chlorate
      respirers, suggesting that chlorate may also control sulfidogenesis by
      biocompetitive exclusion of sulfate-reduction. Perchlorate addition stimulated
      Desulfobulbaceae and Desulfomonadaceae, which contain sulfide oxidizing and
      elemental sulfur-reducing species respectively, suggesting that effluent sulfide
      concentrations may be controlled through sulfur redox cycling in addition to
      toxicity and biocompetitive exclusion. Sulfur isotope analyses further support
      sulfur cycling in the columns, even when sulfide is not detected. This study
      indicates that (per)chlorate show great promise as inhibitors of sulfidogenesis
      in natural communities and provides insight into which organisms and respiratory
      processes are involved. 

PMID- 25071732
TI  - Human decidual macrophages and NK cells differentially express Toll-like
      receptors and display distinct cytokine profiles upon TLR stimulation.
AB  - Maternofetal pathogen transmission is partially controlled at the level of the
      maternal uterine mucosa at the fetal implantation site (the decidua basalis),
      where maternal and fetal cells are in close contact. Toll-like receptors (TLRs)
      may play an important role in initiating rapid immune responses against pathogens
      in the decidua basalis, however the tolerant microenvironment should be preserved
      in order to allow fetal development. Here we investigated the expression and
      functionality of TLRs expressed by decidual macrophages (dMs) and NK cells
      (dNKs), the major decidual immune cell populations. We report for the first time
      that both human dMs and dNK cells express mRNAs encoding TLRs 1-9, albeit with a
      higher expression level in dMs. TLR2, TLR3, and TLR4 protein expression checked
      by flow cytometry was positive for both dMs and dNK cells. In vitro treatment of
      primary dMs and dNK cells with specific TLR2, TLR3, TLR4, TLR7/8, and TLR9
      agonists enhanced their secretion of pro- and anti-inflammatory cytokines, as
      well as cytokines and chemokines involved in immune cell crosstalk. Only dNK
      cells released IFN-gamma, whereas only dMs released IL-1beta, IL-10, and IL-12.
      TLR9 activation of dMs resulted in a distinct pattern of cytokine expression
      compared to the other TLRs. The cytokine profiles expressed by dMs and dNK cells
      upon TLR activation are compatible with maintenance of the fetotolerant immune
      environment during initiation of immune responses to pathogens at the
      maternofetal interface. 

PMID- 25071734
TI  - The filamentous phage XacF1 causes loss of virulence in Xanthomonas axonopodis
      pv. citri, the causative agent of citrus canker disease.
AB  - In this study, filamentous phage XacF1, which can infect Xanthomonas axonopodis
      pv. citri (Xac) strains, was isolated and characterized. Electron microscopy
      showed that XacF1 is a member of the family Inoviridae and is about 600 nm long.
      The genome of XacF1 is 7325 nucleotides in size, containing 13 predicted open
      reading frames (ORFs), some of which showed significant homology to Ff-like phage
      proteins such as ORF1 (pII), ORF2 (pV), ORF6 (pIII), and ORF8 (pVI). XacF1 showed
      a relatively wide host range, infecting seven out of 11 strains tested in this
      study. Frequently, XacF1 was found to be integrated into the genome of Xac
      strains. This integration occurred at the host dif site (attB) and was mediated
      by the host XerC/D recombination system. The attP sequence was identical to that
      of Xanthomonas phage Cf1c. Interestingly, infection by XacF1 phage caused several
      physiological changes to the bacterial host cells, including lower levels of
      extracellular polysaccharide production, reduced motility, slower growth rate,
      and a dramatic reduction in virulence. In particular, the reduction in virulence
      suggested possible utilization of XacF1 as a biological control agent against
      citrus canker disease. 

PMID- 25071733
TI  - Life on the outside: role of biofilms in environmental persistence of Shiga-toxin
      producing Escherichia coli.
AB  - Escherichia coli is a heterogeneous species that can be part of the normal flora
      of humans but also include strains of medical importance. Among pathogenic
      members, Shiga-toxin producing E. coli (STEC) are some of the more prominent
      pathogenic E. coli within the public sphere. STEC disease outbreaks are typically
      associated with contaminated beef, contaminated drinking water, and contaminated
      fresh produce. These water- and food-borne pathogens usually colonize cattle
      asymptomatically; cows will shed STEC in their feces and the subsequent fecal
      contamination of the environment and processing plants is a major concern for
      food and public safety. This is especially important because STEC can survive for
      prolonged periods of time outside its host in environments such as water,
      produce, and farm soil. Biofilms are hypothesized to be important for survival in
      the environment especially on produce, in rivers, and in processing plants.
      Several factors involved in biofilm formation such as curli, cellulose, poly-N
      acetyl glucosamine, and colanic acid are involved in plant colonization and
      adherence to different surfaces often found in meat processing plants. In food
      processing plants, contamination of beef carcasses occurs at different stages of
      processing and this is often caused by the formation of STEC biofilms on the
      surface of several pieces of equipment associated with slaughtering and
      processing. Biofilms protect bacteria against several challenges, including
      biocides used in industrial processes. STEC biofilms are less sensitive than
      planktonic cells to several chemical sanitizers such as quaternary ammonium
      compounds, peroxyacetic acid, and chlorine compounds. Increased resistance to
      sanitizers by STEC growing in a biofilm is likely to be a source of contamination
      in the processing plant. This review focuses on the role of biofilm formation by
      STEC as a means of persistence outside their animal host and factors associated
      with biofilm formation. 

PMID- 25071735
TI  - Varicella-zoster virus glycoprotein expression differentially induces the
      unfolded protein response in infected cells.
AB  - Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as
      varicella or chicken pox. The virus then establishes latency in the nervous
      system and re-emerges, typically decades later, as zoster or shingles. We have
      reported previously that VZV induces autophagy in infected cells as well as
      exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a
      greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. Herein we report
      the results of a UPR specific PCR array that measures the levels of mRNA of 84
      different components of the UPR in VZV infected cells as compared to tunicamycin
      treated cells as a positive control and uninfected, untreated cells as a negative
      control. Tunicamycin is a mixture of chemicals that inhibits N-linked
      glycosylation in the ER with resultant protein misfolding and the UPR. We found
      that VZV differentially induces the UPR when compared to tunicamycin treatment.
      For example, tunicamycin treatment moderately increased (8-fold) roughly half of
      the array elements while downregulating only three (one ERAD and two FOLD
      components). VZV infection on the other hand upregulated 33 components including
      a little described stress sensor CREB-H (64-fold) as well as ER membrane
      components INSIG and gp78, which modulate cholesterol synthesis while
      downregulating over 20 components mostly associated with ERAD and FOLD. We
      hypothesize that this expression pattern is associated with an expanding ER with
      downregulation of active degradation by ERAD and apoptosis as the cell attempts
      to handle abundant viral glycoprotein synthesis. 

PMID- 25071736
TI  - An ortholog of the Leptospira interrogans lipoprotein LipL32 aids in the
      colonization of Pseudoalteromonas tunicata to host surfaces.
AB  - The bacterium Pseudoalteromonas tunicata is a common surface colonizer of marine
      eukaryotes, including the macroalga Ulva australis.Genomic analysis of P.
      tunicata identified genes potentially involved in surface colonization, including
      genes with homology to bacterial virulence factors that mediate attachment. Of
      particular interest is the presence of a gene, designated ptlL32, encoding an
      ortholog to the Leptospira lipoprotein LipL32, which has been shown to facilitate
      the interaction of Leptospira sp. with host extracellular matrix (ECM) structures
      and is thought to be an important virulence trait for pathogenic Leptospira. To
      investigate the role of PtlL32 in the colonization by P. tunicata we constructed
      and characterized a DeltaptlL32 mutant strain. Whilst P. tunicata DeltaptlL32
      bound to an abiotic surface with the same capacity as the wild type strain, it
      had a marked effect on the ability of P. tunicata to bind to ECM, suggesting a
      specific role in attachment to biological surfaces. Loss of PtlL32 also
      significantly reduced the capacity for P. tunciata to colonize the host algal
      surface demonstrating a clear role for this protein as a host-colonization
      factor. PtlL32 appears to have a patchy distribution across specific groups of
      environmental bacteria and phylogenetic analysis of PtlL32 orthologous proteins
      from non-Leptospira species suggests it may have been acquired via horizontal
      gene transfer between distantly related lineages. This study provides the first
      evidence for an attachment function for a LipL32-like protein outside the
      Leptospira and thereby contributes to the understanding of host colonization in
      ecologically distinct bacterial species. 

PMID- 25071737
TI  - Opportunities and challenges in deriving phytoplankton diversity measures from
      individual trait-based data obtained by scanning flow-cytometry.
AB  - In the context of understanding and predicting the effects of human-induced
      environmental change (EC) on biodiversity (BD), and the consequences of BD change
      for ecosystem functioning (EF), microbial ecologists face the challenge of
      linking individual level variability in functional traits to larger-scale
      ecosystem processes. Since lower level BD at genetic, individual, and population
      levels largely determines the functionality and resilience of natural populations
      and communities, individual level measures promise to link EC-induced
      physiological, ecological, and evolutionary responses to EF. Intraspecific trait
      differences, while representing among the least-understood aspects of natural
      microbial communities, have recently become easier to measure due to new
      technology. For example, recent advance in scanning flow-cytometry (SCF),
      automation of phytoplankton sampling and integration with environmental sensors
      allow to measure morphological and physiological traits of individual algae with
      high spatial and temporal resolution. Here we present emerging features of
      automated SFC data from natural phytoplankton communities and the opportunities
      that they provide for understanding the functioning of complex aquatic microbial
      communities. We highlight some current limitations and future needs, particularly
      focusing on the large amount of individual level data that, for the purpose of
      understanding the EC-BD-EF link, need to be translated into meaningful BD
      indices. We review the available functional diversity (FD) indices that, despite
      having been designed for mean trait values at the species level, can be adapted
      to individual-based trait data and provide links to ecological theory. We
      conclude that, considering some computational, mathematical and ecological
      issues, a set of multi-dimensional indices that address richness, evenness and
      divergence in overall community trait space represent the most promising BD
      metrics to study EC-BD-EF using individual level data. 

PMID- 25071738
TI  - Characterization of protein redox dynamics induced during light-to-dark
      transitions and nutrient limitation in cyanobacteria.
AB  - Protein redox chemistry constitutes a major void in knowledge pertaining to
      photoautotrophic system regulation and signaling processes. We have employed a
      chemical biology approach to analyze redox sensitive proteins in live
      Synechococcus sp. PCC 7002 cells in both light and dark periods, and to
      understand how cellular redox balance is disrupted during nutrient perturbation.
      The present work identified 300 putative redox-sensitive proteins that are
      involved in the generation of reductant, macromolecule synthesis, and carbon flux
      through central metabolic pathways, and may be involved in cell signaling and
      response mechanisms. Furthermore, our research suggests that dynamic redox
      changes in response to specific nutrient limitations, including carbon and
      nitrogen limitations, contribute to the regulatory changes driven by a shift from
      light to dark. Taken together, these results contribute to a high-level
      understanding of post-translational mechanisms regulating flux distributions and
      suggest potential metabolic engineering targets for redirecting carbon toward
      biofuel precursors. 

PMID- 25071739
TI  - Nitrogen-fixing Rhizobium-legume symbiosis: are polyploidy and host peptide
      governed symbiont differentiation general principles of endosymbiosis?
AB  - The symbiosis between rhizobia soil bacteria and legumes is facultative and
      initiated by nitrogen starvation of the host plant. Exchange of signal molecules
      between the partners leads to the formation of root nodules where bacteria are
      converted to nitrogen-fixing bacteroids. In this mutualistic symbiosis, the
      bacteria provide nitrogen sources for plant growth in return for photosynthates
      from the host. Depending on the host plant the symbiotic fate of bacteria can
      either be reversible or irreversible. In Medicago plants the bacteria undergo a
      host-directed multistep differentiation process culminating in the formation of
      elongated and branched polyploid bacteria with definitive loss of cell division
      ability. The plant factors are nodule-specific symbiotic peptides. About 500 of
      them are cysteine-rich NCR peptides produced in the infected plant cells. NCRs
      are targeted to the endosymbionts and the concerted action of different sets of
      peptides governs different stages of endosymbiont maturation. This review focuses
      on symbiotic plant cell development and terminal bacteroid differentiation and
      demonstrates the crucial roles of symbiotic peptides by showing an example of
      multi-target mechanism exerted by one of these symbiotic peptides. 

PMID- 25071740
TI  - Pyrosequencing detects human and animal pathogenic taxa in the grapevine
      endosphere.
AB  - Generally, plants are not considered as hosts for human and animal pathogens
      (HAP). The recent produce-associated outbreaks of food-borne diseases have drawn
      attention toward significant deficiencies in our understanding of the ecology of
      HAP, and their potential for interkingdom transfer. To examine the association of
      microorganisms classified as HAP with plants, we surveyed the presence and
      distribution of HAP bacterial taxa (henceforth HAPT, for brevity's sake) in the
      endosphere of grapevine (Vitis vinifera L.) both in the plant stems and leaves.
      An enrichment protocol was used on leaves to detect taxa with very low abundance
      in undisturbed tissues. We used pyrosequencing and phylogenetic analyses of the
      16S rDNA gene. We identified several HAPT, and focused on four genera
      (Propionibacterium, Staphylococcus, Clostridium, and Burkholderia). The majority
      of the bacterial sequences in the genus Propionibacterium, from grapevine leaf
      and stem, were identified as P. acnes. Clostridia were detected in leaves and
      stems, but their number was much higher in leaves after enrichment. HAPT were
      indentified both in leaves and wood of grapevines. This depicts the ability of
      these taxa to be internalized within plant tissues and maintain their population
      levels in a variety of environments. Our analysis highlighted the presence of
      HAPT in the grapevine endosphere and unexpected occurrence of these bacterial
      taxa in this atypical environment. 

PMID- 25071742
TI  - Challenges to the development of vaccines to hepatitis C virus that elicit
      neutralizing antibodies.
AB  - Despite 20 years of research, a vaccine to prevent hepatitis C virus (HCV)
      infection has not been developed. A vaccine to prevent HCV will need to induce
      broadly reactive immunity able to prevent infection by the 7 genetically and
      antigenically distinct genotypes circulating world-wide. HCV encodes two surface
      exposed glycoproteins, E1 and E2 that function as a heterodimer to mediate viral
      entry. Neutralizing antibodies (NAbs) to both E1 and E2 have been described with
      the major NAb target being E2. The function of E2 is to attach virions to host
      cells via cell surface receptors that include, but is not limited to, the
      tetraspanin CD81 and scavenger receptor class B type 1. However, E2 has developed
      a number of immune evasion strategies to limit the effectiveness of the NAb
      response and possibly limit the ability of the immune system to generate potent
      NAbs in natural infection. Hypervariable regions that shield the underlying core
      domain, subdominant neutralization epitopes and glycan shielding combine to make
      E2 a difficult target for the immune system. This review summarizes recent
      information on the role of NAbs to prevent HCV infection, the targets of the NAb
      response and structural information on glycoprotein E2 in complex with
      neutralizing antibodies. This new information should provide a framework for the
      rational design of new vaccine candidates that elicit highly potent broadly
      reactive NAbs to prevent HCV infection. 

PMID- 25071741
TI  - Intercellular communications in multispecies oral microbial communities.
AB  - The oral cavity contains more than 700 microbial species that are engaged in
      extensive cell-cell interactions. These interactions contribute to the formation
      of highly structured multispecies communities, allow them to perform
      physiological functions, and induce synergistic pathogenesis. Co-adhesion between
      oral microbial species influences their colonization of oral cavity and
      effectuates, to a large extent, the temporal and spatial formation of highly
      organized polymicrobial community architecture. Individual species also compete
      and collaborate with other neighboring species through metabolic interactions,
      which not only modify the local microenvironment such as pH and the amount of
      oxygen, making it more suitable for the growth of other species, but also provide
      a metabolic framework for the participating microorganisms by maximizing their
      potential to extract energy from limited substrates. Direct physical contact of
      bacterial species with its neighboring co-habitants within microbial community
      could initiate signaling cascade and achieve modulation of gene expression in
      accordance with different species it is in contact with. In addition to
      communication through cell-cell contact, quorum sensing (QS) mediated by small
      signaling molecules such as competence-stimulating peptides (CSPs) and
      autoinducer-2 (AI-2), plays essential roles in bacterial physiology and ecology.
      This review will summarize the evidence that oral microbes participate in
      intercellular communications with co-inhabitants through cell contact-dependent
      physical interactions, metabolic interdependencies, as well as coordinative
      signaling systems to establish and maintain balanced microbial communities. 

PMID- 25071744
TI  - 16S rDNA-based analysis reveals cosmopolitan occurrence but limited diversity of
      two cyanobacterial lineages with contrasted patterns of intracellular carbonate
      mineralization.
AB  - Cyanobacteria are mainly thought to induce carbonate precipitation
      extracellularly via their photosynthetic activity combined with the nucleation
      potential of exopolymeric substances. The discovery in microbialites of the
      alkaline lake Alchichica (Mexico) of Candidatus Gloeomargarita lithophora, a
      cyanobacterium forming large amounts of intracellular Mg-Ca-Sr-Ba carbonate
      spherules, showed that intracellular biomineralization in cyanobacteria is also
      possible. A second cyanobacterium isolated from the same environment, Candidatus
      Synechococcus calcipolaris G9, has been recently shown to also form intracellular
      calcium carbonates at the cell poles, a capability shared by all cultured species
      of the Thermosynechococcus clade, to which it belongs. To explore the diversity
      of these two distant cyanobacterial lineages representing two different patterns
      of intracellular calcification, we designed specific primers against their 16S
      rRNA genes and looked for their occurrence in a wide variety of samples. We
      identified the presence of members of the Gloeomargarita and
      Thermosynechococcus/S. calcipolaris lineages in microbialites collected from Lake
      Alchichica and three other neighboring Mexican lakes. The two clades also
      occurred in karstic areas and in some thermophilic or hypersaline microbial mats
      collected in South America and/or Southern Europe. Surprisingly, the within-group
      diversity in the two clades was low, especially within the S. calcipolaris clade,
      with all 16S rRNA gene sequences retrieved sharing more than 97% identity. This
      suggests that these clades are composed of a limited number of operational
      taxonomic units (OTUs) with cosmopolitan distribution. Moreover, scanning
      electron microscopy coupled with energy dispersive x-ray spectrometry showed the
      presence of intracellularly calcifying Gloeomargarita-like cyanobacteria in fresh
      samples where this clade was relatively abundant, suggesting that these
      cyanobacteria do precipitate carbonates intracellularly under natural conditions.

PMID- 25071745
TI  - Single-cell genomics reveals features of a Colwellia species that was dominant
      during the Deepwater Horizon oil spill.
AB  - During the Deepwater Horizon (DWH) oil spill in the Gulf of Mexico a deep-sea
      hydrocarbon plume developed resulting in a rapid succession of bacteria.
      Colwellia eventually supplanted Oceanospirillales, which dominated the plume
      early in the spill. These successional changes may have resulted, in part, from
      the changing composition and abundance of hydrocarbons over time. Colwellia
      abundance peaked when gaseous and simple aromatic hydrocarbons increased, yet the
      metabolic pathway used by Colwellia in hydrocarbon disposition is unknown. Here
      we used single-cell genomics to gain insights into the genome properties of a
      Colwellia enriched during the DWH deep-sea plume. A single amplified genome (SAG)
      of a Colwellia cell isolated from a DWH plume, closely related (avg. 98% 16S rRNA
      gene similarity) to other plume Colwellia, was sequenced and annotated. The SAG
      was similar to the sequenced isolate Colwellia psychrerythraea 34H (84% avg.
      nucleotide identity). Both had genes for denitrification, chemotaxis, and
      motility, adaptations to cold environments and a suite of nutrient acquisition
      genes. The Colwellia SAG may be capable of gaseous and aromatic hydrocarbon
      degradation, which contrasts with a DWH plume Oceanospirillales SAG which encoded
      non-gaseous n-alkane and cycloalkane degradation pathways. The disparate
      hydrocarbon degradation pathways are consistent with hydrocarbons that were
      abundant at different times in the deep-sea plume; first, non-gaseous n-alkanes
      and cycloalkanes that could be degraded by Oceanospirillales, followed by
      gaseous, and simple aromatic hydrocarbons that may have been degraded by
      Colwellia. These insights into the genomic properties of a Colwellia species,
      which were supported by existing metagenomic sequence data from the plume and DWH
      contaminated sediments, help further our understanding of the successional
      changes in the dominant microbial players in the plume over the course of the DWH
      spill. 

PMID- 25071743
TI  - ERAD and how viruses exploit it.
AB  - Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally
      important process among eukaryotic cells. ERAD is necessary to preserve cell
      integrity since the accumulation of defective proteins results in diseases
      associated with neurological dysfunction, cancer, and infections. This process
      involves recognition of misfolded or misassembled proteins that have been
      translated in association with ER membranes. Recognition of ERAD substrates leads
      to their extraction through the ER membrane (retrotranslocation or dislocation),
      ubiquitination, and destruction by cytosolic proteasomes. This review focuses on
      ERAD and its components as well as how viruses use this process to promote their
      replication and to avoid the immune response. 

PMID- 25071747
TI  - Use of antibiotics as feed additives: a burning question.

PMID- 25071746
TI  - Pinus flexilis and Picea engelmannii share a simple and consistent needle
      endophyte microbiota with a potential role in nitrogen fixation.
AB  - Conifers predominantly occur on soils or in climates that are suboptimal for
      plant growth. This is generally attributed to symbioses with mycorrhizal fungi
      and to conifer adaptations, but recent experiments suggest that aboveground
      endophytic bacteria in conifers fix nitrogen (N) and affect host shoot tissue
      growth. Because most bacteria cannot be grown in the laboratory very little is
      known about conifer-endophyte associations in the wild. Pinus flexilis (limber
      pine) and Picea engelmannii (Engelmann spruce) growing in a subalpine, nutrient
      limited environment are potential candidates for hosting endophytes with roles in
      N2 fixation and abiotic stress tolerance. We used 16S rRNA pyrosequencing to ask
      whether these conifers host a core of bacterial species that are consistently
      associated with conifer individuals and therefore potential mutualists. We found
      that while overall the endophyte communities clustered according to host species,
      both conifers were consistently dominated by the same phylotype, which made up 19
      53% and 14-39% of the sequences in P. flexilis and P. engelmannii, respectively.
      This phylotype is related to Gluconacetobacter diazotrophicus and other N2 fixing
      acetic acid bacterial endophytes. The pattern observed for the P. flexilis and P.
      engelmannii needle microbiota-a small number of major species that are
      consistently associated with the host across individuals and species-is
      unprecedented for an endophyte community, and suggests a specialized beneficial
      endophyte function. One possibility is endophytic N fixation, which could help
      explain how conifers can grow in severely nitrogen-limited soil, and why some
      forest ecosystems accumulate more N than can be accounted for by known nitrogen
      input pathways. 

PMID- 25071748
TI  - A genomic approach to coral-dinoflagellate symbiosis: studies of Acropora
      digitifera and Symbiodinium minutum.
AB  - Far more intimate knowledge of scleractinian coral biology is essential in order
      to understand how diverse coral-symbiont endosymbioses have been established. In
      particular, molecular and cellular mechanisms enabling the establishment and
      maintenance of obligate endosymbiosis with photosynthetic dinoflagellates require
      further clarification. By extension, such understanding may also shed light upon
      environmental conditions that promote the collapse of this mutualism. Genomic
      data undergird studies of all symbiotic processes. Here we review recent genomic
      data derived from the scleractinian coral, Acropora digitifera, and the
      endosymbiotic dinoflagellate, Symbiodinium minutum. We discuss Acropora genes
      involved in calcification, embryonic development, innate immunity, apoptosis,
      autophagy, UV resistance, fluorescence, photoreceptors, circadian clocks, etc. We
      also detail gene loss in amino acid metabolism that may explain at least part of
      the Acropora stress-response. Characteristic features of the Symbiodinium genome
      are also reviewed, focusing on the expansion of certain gene families, the
      molecular basis for permanently condensed chromatin, unique spliceosomal
      splicing, and unusual gene arrangement. Salient features of the Symbiodinium
      plastid and mitochondrial genomes are also illuminated. Although many questions
      regarding these interdependent genomes remain, we summarize information necessary
      for future studies of coral-dinoflagellate endosymbiosis. 

PMID- 25071749
TI  - Modulation of dendritic cell functions by viral IL-10 encoded by human
      cytomegalovirus.
AB  - Human cytomegalovirus (HCMV), a clinically important beta-herpesvirus, is a
      master of evasion and modulation of the host immune system, including inhibition
      of a number of dendritic cell (DC) functions. DCs play a central role in co
      ordination of the immune response against pathogens and any disturbance of DCs
      functions can result in a cascade effect on a range of immune cells. Recently,
      the HCMV gene UL111A, which encodes viral homologs of human interleukin 10, has
      been identified as a strong suppressor of a number of DCs functions. In this mini
      review, we focus on HCMV-encoded viral IL-10-mediated inhibitory effects on DCs
      and implications for the development of an effective HCMV vaccine. 

PMID- 25071750
TI  - Lactobacillus helveticus: importance in food and health.

PMID- 25071751
TI  - The IL-8 protease SpyCEP is detrimental for Group A Streptococcus host-cells
      interaction and biofilm formation.
AB  - SpyCEP-mediated chemokine degradation translates into more efficient spreading
      and increased severity of invasive Group A Streptococcus (GAS) infections, due to
      impaired neutrophil recruitment to the site of infection. SpyCEP is markedly up
      regulated in invasive as compared to colonizing GAS isolates raising the question
      whether SpyCEP expression hinders bacterial attachment and thus colonization of
      the host. To address this question we used a molecular approach involving the use
      of homologous GAS strains either expressing or not SpyCEP or expressing an
      enzymatically inactive variant of SpyCEP. We found that expression of
      enzymatically functional SpyCEP lowered GAS adherence and invasion potential
      toward various epithelial and endothelial cells. SpyCEP also blunted biofilm
      formation capacity. Our data indicate that expression of SpyCEP decreases
      colonization and thus might be detrimental for the spreading of GAS. 

PMID- 25071752
TI  - Recombinant protein expression in microbial systems.

PMID- 25071753
TI  - Persistence in the shadow of killers.
AB  - Killing is perhaps the most definite form of communication possible. Microbes
      such as yeasts and gut bacteria have been shown to exhibit killer phenotypes. The
      killer strains are able to kill other microbes occupying the same ecological
      niche, and do so with impunity. It would therefore be expected that, wherever a
      killer phenotype has arisen, all members of the population would soon be killers
      or dead. Surprisingly, (1) one can find both killer and sensitive strains in
      coexistence, both in the wild and in in vitro experiments, and (2) the absolute
      fitness cost of the killer phenotype often seems to be very small. We present an
      explicit model of such coexistence in a fragmented or discrete environment. A
      killer strain may kill all sensitive cells in one patch (one piece of rotting
      fruit, one cave or one human gut, for example), allowing sensitives to exist only
      in the absence of killer strains on the same patch. In our model, populations
      spread easily between patches, but in a stochastic manner: one can imagine spores
      borne by the wind over a field of untended apple trees, or enteric disease
      transmission in a region in which travel is effectively unrestricted. What we
      show is that coexistence is not only possible, but that it is possible even if
      the absolute fitness advantage of the sensitive strain over the killer strain is
      arbitrarily small. We do this by performing a specifically targeted mathematical
      analysis on our model, rather than via simulations. Our model does not assume
      large population densities, and may thus be useful in the context of
      understanding the ecology of extreme environments. 

PMID- 25071754
TI  - Biofuel production: an odyssey from metabolic engineering to fermentation scale
      up.
AB  - Metabolic engineering has developed microbial cell factories that can convert
      renewable carbon sources into biofuels. Current molecular biology tools can
      efficiently alter enzyme levels to redirect carbon fluxes toward biofuel
      production, but low product yield and titer in large bioreactors prevent the
      fulfillment of cheap biofuels. There are three major roadblocks preventing
      economical biofuel production. First, carbon fluxes from the substrate dissipate
      into a complex metabolic network. Besides the desired product, microbial hosts
      direct carbon flux to synthesize biomass, overflow metabolites, and heterologous
      enzymes. Second, microbial hosts need to oxidize a large portion of the substrate
      to generate both ATP and NAD(P)H to power biofuel synthesis. High cell
      maintenance, triggered by the metabolic burdens from genetic modifications, can
      significantly affect the ATP supply. Thereby, fermentation of advanced biofuels
      (such as biodiesel and hydrocarbons) often requires aerobic respiration to
      resolve the ATP shortage. Third, mass transfer limitations in large bioreactors
      create heterogeneous growth conditions and micro-environmental fluctuations (such
      as suboptimal O2 level and pH) that induce metabolic stresses and genetic
      instability. To overcome these limitations, fermentation engineering should merge
      with systems metabolic engineering. Modern fermentation engineers need to adopt
      new metabolic flux analysis tools that integrate kinetics, hydrodynamics, and
      (13)C-proteomics, to reveal the dynamic physiologies of the microbial host under
      large bioreactor conditions. Based on metabolic analyses, fermentation engineers
      may employ rational pathway modifications, synthetic biology circuits, and
      bioreactor control algorithms to optimize large-scale biofuel production. 

PMID- 25071755
TI  - Metagenomic analysis of a sample from a patient with respiratory tract infection
      reveals the presence of a gamma-papillomavirus.
AB  - Previously unknown or unexpected pathogens may be responsible for that proportion
      of respiratory diseases in which a causative agent cannot be identified. The
      application of broad-spectrum, sequence independent virus discovery techniques
      may be useful to reduce this proportion and widen our knowledge about respiratory
      pathogens. Thanks to the availability of high-throughput sequencing (HTS)
      technology, it became today possible to detect viruses which are present at a
      very low load, but the clinical relevance of those viruses must be investigated.
      In this study we used VIDISCA-454, a restriction enzyme based virus discovery
      method that utilizes Roche 454 HTS system, on a nasal swab collected from a
      subject with respiratory complaints. A gamma-papillomavirus was detected
      (complete genome: 7142 bp) and its role in disease was investigated. Respiratory
      samples collected both during the acute phase of the illness and 2 weeks after
      full recovery contained the virus. The patient presented antibodies directed
      against the virus but there was no difference between IgG levels in blood samples
      collected during the acute phase and 2 weeks after full recovery. We therefore
      concluded that the detected gamma-papillomavirus is unlikely to be the causative
      agent of the respiratory complaints and its presence in the nose of the patient
      is not related to the disease. Although HTS based virus discovery techniques
      proved their great potential as a tool to clarify the etiology of some infectious
      diseases, the obtained information must be subjected to cautious interpretations.
      This study underlines the crucial importance of performing careful investigations
      on viruses identified when applying sensitive virus discovery techniques, since
      the mere identification of a virus and its presence in a clinical sample are not
      satisfactory proofs to establish a causative link with a disease. 

PMID- 25071756
TI  - Nutrient cross-feeding in the microbial world.
AB  - The stability and function of a microbial community depends on nutritional
      interactions among community members such as the cross-feeding of essential small
      molecules synthesized by a subset of the population. In this review, we describe
      examples of microbe-microbe and microbe-host cofactor cross-feeding, a type of
      interaction that influences the forms of metabolism carried out within a
      community. Cofactor cross-feeding can contribute to both the health and nutrition
      of a host organism, the virulence and persistence of pathogens, and the
      composition and function of environmental communities. By examining the impact of
      shared cofactors on microbes from pure culture to natural communities, we stand
      to gain a better understanding of the interactions that link microbes together,
      which may ultimately be a key to developing strategies for manipulating microbial
      communities with human health, agricultural, and environmental implications. 

PMID- 25071757
TI  - Biofilm formation of mucosa-associated methanoarchaeal strains.
AB  - Although in nature most microorganisms are known to occur predominantly in
      consortia or biofilms, data on archaeal biofilm formation are in general scarce.
      Here, the ability of three methanoarchaeal strains, Methanobrevibacter smithii
      and Methanosphaera stadtmanae, which form part of the human gut microbiota, and
      the Methanosarcina mazei strain Go1 to grow on different surfaces and form
      biofilms was investigated. All three strains adhered to the substrate mica and
      grew predominantly as bilayers on its surface as demonstrated by confocal laser
      scanning microscopy analyses, though the formation of multi-layered biofilms of
      Methanosphaera stadtmanae and Methanobrevibacter smithii was observed as well.
      Stable biofilm formation was further confirmed by scanning electron microscopy
      analysis. Methanosarcina mazei and Methanobrevibacter smithii also formed multi
      layered biofilms in uncoated plastic MU-dishes(TM), which were very similar in
      morphology and reached a height of up to 40 MUm. In contrast, biofilms formed by
      Methanosphaera stadtmanae reached only a height of 2 MUm. Staining with the two
      lectins ConA and IB4 indicated that all three strains produced relatively low
      amounts of extracellular polysaccharides most likely containing glucose, mannose,
      and galactose. Taken together, this study provides the first evidence that
      methanoarchaea can develop and form biofilms on different substrates and thus,
      will contribute to our knowledge on the appearance and physiological role of
      Methanobrevibacter smithii and Methanosphaera stadtmanae in the human intestine. 

PMID- 25071758
TI  - Induction of Multiple Immune Regulatory Pathways with Differential Impact in
      HCV/HIV Coinfection.
AB  - Persistent viral infections including HCV, HBV, and HIV are associated with
      increased immune regulatory pathways including the extrinsic FoxP3+CD4+
      regulatory T cells (Tregs) and intrinsic inhibitory pathways such as programed
      death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) with potentially
      reversible suppression of antiviral effector T cells (1-12). Immunological
      consequences of viral coinfections relative to these immune regulatory pathways
      and their interplay are not well-defined. In this study, we examined the
      frequency, phenotype, and effector function of circulating T cell subsets in
      patients with chronic HCV and/or HIV infection, hypothesizing that HCV/HIV
      coinfection will result in greater immune dysregulation with pathogenetic
      consequences (13, 14). We show that multiple T cell inhibitory pathways are
      induced in HCV/HIV coinfection including FoxP3+ Tregs, PD-1, and CTLA-4 in
      inverse association with overall CD4 T cell frequency but not with liver function
      or HCV RNA titers. The inverse association between CD4 T cell frequency and their
      FoxP3, PD-1, or CTLA-4 expression remained significant in all subjects combined
      regardless of HCV and/or HIV infection, suggesting a global homeostatic mechanism
      to maintain immune regulation relative to CD4 T cell frequency. PD-1 blockade
      rescued T cell responses to HIV but not HCV without significant impact by CTLA-4
      blockade in vitro. Collectively, these findings highlight complex immune
      interactions in viral coinfections and differential regulatory pathways
      influencing virus-specific T cells that are relevant in immunotherapeutic
      development. 

PMID- 25071759
TI  - Embryonic Stem Cells Promoting Macrophage Survival and Function are Crucial for
      Teratoma Development.
AB  - Stem cell therapies have had tremendous potential application for many diseases
      in recent years. However, the tumorigenic properties of stem cells restrict their
      potential clinical application; therefore, strategies for reducing the
      tumorigenic potential of stem cells must be established prior to transplantation.
      We have demonstrated that syngeneic transplantation of embryonic stem cells
      (ESCs) provokes an inflammatory response that involves the rapid recruitment of
      bone marrow-derived macrophages (BMDMs). ESCs are able to prevent mature
      macrophages from macrophage colony-stimulating factor (M-CSF) withdrawal-induced
      apoptosis, and thus prolong macrophage lifespan significantly by blocking various
      apoptotic pathways in an M-CSF-independent manner. ESCs express and secrete IL
      34, which may be responsible for ESC-promoted macrophage survival. This anti
      apoptotic effect of ESCs involves activation of extracellular signal-regulated
      kinase (ERK)1/2 and PI3K/Akt pathways and thus, inhibition of ERK1/2 and PI3K/AKT
      activation decreases ESC-induced macrophage survival. Functionally, ESC-treated
      macrophages also showed a higher level of phagocytic activity. ESCs further serve
      to polarize BMDMs into M2-like macrophages that exhibit most tumor-associated
      macrophage phenotypic and functional features. ESC-educated macrophages produce
      high levels of arginase-1, Tie-2, and TNF-alpha, which participate in
      angiogenesis and contribute to teratoma progression. Our study suggests that
      induction of M2-like macrophage activation is an important mechanism for teratoma
      development. Strategies targeting macrophages to inhibit teratoma development
      would increase the safety of ESC-based therapies, inasmuch as the depletion of
      macrophages completely inhibits ESC-induced angiogenesis and teratoma
      development. 

PMID- 25071760
TI  - Mucosal SIV Vaccines Comprising Inactivated Virus Particles and Bacterial
      Adjuvants Induce CD8(+) T-Regulatory Cells that Suppress SIV-Positive CD4(+) T
      Cell Activation and Prevent SIV Infection in the Macaque Model.
AB  - A new paradigm of mucosal vaccination against human immunodeficiency virus (HIV)
      infection has been investigated in the macaque model. A vaccine consisting of
      inactivated simian immunodeficiency virus (SIV)mac239 particles together with a
      living bacterial adjuvant (either the Calmette and Guerin bacillus, Lactobacillus
      plantarum or Lactobacillus rhamnosus) was administered to macaques via the
      vaginal or oral/intragastric route. In contrast to all established human and
      veterinary vaccines, these three vaccine regimens did not elicit SIV-specific
      antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized
      population of non-cytolytic MHCIb/E-restricted CD8(+) T-regulatory cells that
      suppressed the activation of SIV-positive CD4(+) T-lymphocytes. SIV reverse
      transcription was thereby blocked in inactivated CD4(+) T-cells; the initial
      burst of virus replication was prevented and the vaccinated macaques were
      protected from a challenge infection. For 3-14 months after intragastric
      immunization, 24 macaques were challenged intrarectally with a high dose of
      SIVmac239 or with the heterologous strain SIV B670 (both strains grown on
      macaques PBMC). Twenty-three of these animals were found to be protected for up
      to 48 months while all 24 control macaques became infected. This protective
      effect against SIV challenge together with the concomitant identification of a
      robust ex vivo correlate of protection suggests a new approach for developing an
      HIV vaccine in humans. The induction of this new class of CD8(+) T-regulatory
      cells could also possibly be used therapeutically for suppressing HIV replication
      in infected patients and this novel tolerogenic vaccine paradigm may have
      potential applications for treating a wide range of immune disorders and is
      likely to may have profound implications across immunology generally. 

PMID- 25071762
TI  - Sinister self-sacrifice: the contribution of apoptosis to malignancy.

PMID- 25071761
TI  - Monocytes and macrophages in pregnancy and pre-eclampsia.
AB  - Preeclampsia is an important complication in pregnancy, characterized by
      hypertension and proteinuria in the second half of pregnancy. Generalized
      activation of the inflammatory response is thought to play a role in the
      pathogenesis of pre-eclampsia. Monocytes may play a central role in this
      inflammatory response. Monocytes are short lived cells that mature in the
      circulation and invade into tissues upon an inflammatory stimulus and develop
      into macrophages. Macrophages are abundantly present in the endometrium and play
      a role in implantation and placentation in normal pregnancy. In pre-eclampsia,
      these macrophages appear to be present in larger numbers and are also activated.
      In the present review, we focused on the role of monocytes and macrophages in the
      pathophysiology of pre-eclampsia. 

PMID- 25071764
TI  - Evolution of Our Understanding of Myeloid Regulatory Cells: From MDSCs to Mregs.
AB  - The term myeloid-derived suppressor cells (MDSCs) was first suggested in 2007 in
      order to reflect the origin and function of myeloid cells during
      immunosuppression in cancer and other pathologic conditions. Emerging evidence
      suggests that MDSCs suppress CTL and Th1 responses in malignant diseases while
      they regulate effective immune responses in parasitic and helminth infections as
      well as Th17 inflammatory response during autoimmune diseases. Based on these
      data, the term myeloid regulatory cells (Mregs) more accurately reflects their
      function and interactions with different cells of the immune system during
      diseased conditions. Here, we provide evidence on the multifaceted function of
      Mregs during diseased states. 

PMID- 25071763
TI  - Eosinophils in the lung - modulating apoptosis and efferocytosis in airway
      inflammation.
AB  - Due to the key role of the lung in efficient transfer of oxygen in exchange for
      carbon dioxide, a controlled inflammatory response is essential for restoration
      of tissue homeostasis following airway exposure to bacterial pathogens or
      environmental toxins. Unregulated or prolonged inflammatory responses in the
      lungs can lead to tissue damage, disrupting normal tissue architecture, and
      consequently compromising efficient gaseous exchange. Failure to resolve
      inflammation underlies the development and/or progression of a number of
      inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of
      the innate immune system, are primarily involved in defense against parasitic
      infections. However, the propagation of the allergic inflammatory response in
      chronic asthma is thought to involve excessive recruitment and impaired apoptosis
      of eosinophils together with defective phagocytic clearance of apoptotic cells
      (efferocytosis). In terms of therapeutic approaches for the treatment of asthma,
      the widespread use of glucocorticoids is associated with a number of adverse
      health consequences after long-term use, while some patients suffer from steroid
      resistant disease. A new approach for therapeutic intervention would be to
      promote the resolution of inflammation via modulation of eosinophil apoptosis and
      the phagocytic clearance of apoptotic cells. This review focuses on the
      mechanisms underpinning eosinophil-mediated lung damage, currently available
      treatments and therapeutic targets that might in future be harnessed to
      facilitate inflammation resolution by the manipulation of cell survival and
      clearance pathways. 

PMID- 25071765
TI  - Extracellular adenosine-mediated modulation of regulatory T cells.
AB  - Extracellular adenosine-dependent suppression and redirection of pro-inflammatory
      activities are mediated by the signaling through adenosine receptors on the
      surface of most immune cells. The immunosuppression by endogenously-produced
      adenosine is pathophysiologically significant since inactivation of A2A/A2B
      adenosine receptor (A2AR/A2BR) and adenosine-producing ecto-enzymes CD39/CD73
      results in the higher intensity of immune response and exaggeration of
      inflammatory damage. Regulatory T cells (Treg) can generate extracellular
      adenosine, which is implicated in the immunoregulatory activity of Tregs.
      Interestingly, adenosine has been shown to increase the numbers of Tregs and
      further promotes their immunoregulatory activity. A2AR-deficiency in Tregs
      reduces their immunosuppressive efficacy in vivo. Thus, adenosine is not only
      directly and instantly inhibiting to the immune response through interaction with
      A2AR/A2BR on the effector cells, but also adenosine signaling can recruit other
      immunoregulatory mechanisms, including Tregs. Such interaction between adenosine
      and Tregs suggests the presence of a positive feedback mechanism, which further
      promotes negative regulation of immune system through the establishment of
      immunosuppressive microenvironment. 

PMID- 25071767
TI  - Type I interferon in human autoimmunity.

PMID- 25071766
TI  - Baseline and Dynamic Expression of Activating NK Cell Receptors in the Control of
      Chronic Viral Infections: The Paradigm of HIV-1 and HCV.
AB  - Natural killer (NK) cell function is regulated by a balance between the
      triggering of activating and inhibitory receptors expressed on their surface. A
      relevant effort has been focused so far on the study of KIR carriage/expression
      setting the basis for NK cell education and self-tolerance. Focus on the
      evolution and regulation of activating NK receptors has lagged behind so far. Our
      understanding of activating receptor expression and regulation has recently
      improved by evidences derived from in vitro and in vivo studies. Virus infection 
      either acute or chronic - determines preferential expansion of NK cells with
      specific phenotype, activating receptors, and with recall-like functional
      activity. Studies on patients with viral infection (HIV and HCV) and specific
      diverging clinical courses confirm that inter-individual differences may exist in
      baseline expression of natural cytotoxicity receptors (NKp46 and NKp30). The
      findings that patients with divergent clinical courses have different kinetics of
      activating receptor density expression upon NK cell activation in vitro provide
      an additional, time-dependent, functional parameter. Kinetic changes in receptor
      expression thus represent an additional parameter to basal receptor density
      expression. Different expression and inducibilities of activating receptors on NK
      cells contribute to the high diversity of NK cell populations and may help our
      understanding of the inter-individual differences in innate responses that
      underlie divergent disease courses. 

PMID- 25071768
TI  - Heat shock protein 70 serum levels differ significantly in patients with chronic
      hepatitis, liver cirrhosis, and hepatocellular carcinoma.
AB  - Members of the heat shock protein 70 (HSP70) family play an important role in
      assisting protein folding, preventing protein aggregation and transport of
      proteins across membranes under physiological conditions. Following environmental
      (i.e., irradiation, chemotherapy), physiological (i.e., cell growth,
      differentiation), and pathophysiological (i.e., inflammation, tumorigenesis)
      stress, the synthesis of heat shock proteins (HSPs) is highly up-regulated,
      whereas protein synthesis in general is reduced. In contrast to normal cells,
      many tumor entities including hepatocellular carcinoma (HCC) overexpress HSP70,
      the major-stress-inducible member of the HSP70 family, present it on their cell
      surface and secrete it into the extracellular milieu. Herein, the prognostic
      relevance of serum HSP70 levels in patients with chronic hepatitis (CH; n = 50),
      liver cirrhosis (LC; n = 46), and HCC (n = 47) was analyzed. Similar to other
      tumor entities, HSP70 is also present on the surface of primary HCC cells. The
      staining intensity of intracellular HSP70 in HCC tissue is stronger compared to
      control and cirrhotic liver sections. HSP70 serum levels in all HCC patients were
      significantly higher compared to a control group without liver disease (n = 40).
      No significant age- and gender-related differences in HSP70 serum levels were
      observed in male and female healthy human volunteers (n = 86). Patients with CH
      (n = 50) revealed significantly higher HSP70 serum levels compared to the control
      group, however, these values were significantly lower than those of HCC patients
      (n = 47). Furthermore, a subgroup of patients with LC who subsequently developed
      HCC (LC-HCC, n = 13) revealed higher HSP70 serum levels than patients with LC (n
      = 46, p = 0.05). These data indicate that serum HSP70 levels are consecutively
      increased in patients with CH, LC and liver carcinomas and thus might have a
      prognostic value. 

PMID- 25071769
TI  - Carbohydrate-mimetic peptides for pan anti-tumor responses.
AB  - Molecular mimicry is fundamental to biology and transcends to many disciplines
      ranging from immune pathology to drug design. Structural characterization of
      molecular partners has provided insight into the origins and relative importance
      of complementarity in mimicry. Chemical complementarity is easy to understand;
      amino acid sequence similarity between peptides, for example, can lead to cross
      reactivity triggering similar reactivity from their cognate receptors. However,
      conformational complementarity is difficult to decipher. Molecular mimicry of
      carbohydrates by peptides is often considered one of those. Extensive studies of
      innate and adaptive immune responses suggests the existence of carbohydrate
      mimicry, but the structural basis for this mimicry yields confounding details;
      peptides mimicking carbohydrates in some cases fail to exhibit both chemical and
      conformational mimicry. Deconvolution of these two types of complementarity in
      mimicry and its relationship to biological function can nevertheless lead to new
      therapeutics. Here, we discuss our experience examining the immunological aspects
      and implications of carbohydrate-peptide mimicry. Emphasis is placed on the
      rationale, the lessons learned from the methodologies to identify mimics, a
      perspective on the limitations of structural analysis, the biological
      consequences of mimicking tumor-associated carbohydrate antigens, and the notion
      of reverse engineering to develop carbohydrate-mimetic peptides in vaccine design
      strategies to induce responses to glycan antigens expressed on cancer cells. 

PMID- 25071770
TI  - Emerging Concepts about NAIP/NLRC4 Inflammasomes.
AB  - Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a
      caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes
      are activated in response to proteins from virulent bacteria that reach the cell
      cytosol. Specific NAIP proteins bind to the agonists and then physically
      associate with NLRC4 to form an inflammasome complex able to recruit and activate
      pro-caspase-1. NAIP5 and NAIP6 sense flagellin, component of flagella from motile
      bacteria, whereas NAIP1 and NAIP2 detect needle and rod components from bacterial
      type III secretion systems, respectively. Active caspase-1 mediates the
      maturation and secretion of the pro-inflammatory cytokines, IL-1beta and IL-18,
      and is responsible for the induction of pyroptosis, a pro-inflammatory form of
      cell death. In addition to these well-known effector mechanisms, novel roles have
      been described for NAIP/NLRC4 inflammasomes, such as phagosomal maturation,
      activation of inducible nitric oxide synthase, regulation of autophagy, secretion
      of inflammatory mediators, antibody production, activation of T cells, among
      others. These effector mechanisms mediated by NAIP/NLRC4 inflammasomes have been
      extensively studied in the context of resistance of infections and the potential
      of their agonists has been exploited in therapeutic strategies to non-infectious
      pathologies, such as tumor protection. Thus, this review will discuss current
      knowledge about the activation of NAIP/NLRC4 inflammasomes and their effector
      mechanisms. 

PMID- 25071772
TI  - Mucosal Inflammatory Response to Salmonella typhimurium Infection.
AB  - The human intestinal epithelium consists of a single layer of epithelial cells
      that forms a barrier against food antigens and the resident microbiota within the
      lumen. This delicately balanced organ functions in a highly sophisticated manner
      to uphold the fidelity of the intestinal epithelium and to eliminate pathogenic
      microorganisms. On the luminal side, this barrier is fortified by a thick mucus
      layer, and on the serosal side exists the lamina propria containing a resident
      population of immune cells. Pathogens that are able to breach this barrier
      disrupt the healthy epithelial lining by interfering with the regulatory
      mechanisms that govern the normal balance of intestinal architecture and
      function. This disruption results in a coordinated innate immune response
      deployed to eliminate the intruder that includes the release of antimicrobial
      peptides, activation of pattern-recognition receptors, and recruitment of a
      variety of immune cells. In the case of Salmonella enterica serovar typhimurium
      (S. typhimurium) infection, induction of an inflammatory response has been linked
      to its virulence mechanism, the type III secretion system (T3SS). The T3SS
      secretes protein effectors that exploit the host's cell biology to facilitate
      bacterial entry and intracellular survival, and to modulate the host immune
      response. As the role of the intestinal epithelium in initiating an immune
      response has been increasingly realized, this review will highlight recent
      research that details progress made in understanding mechanisms underlying the
      mucosal inflammatory response to Salmonella infection, and how such inflammatory
      responses impact pathogenic fitness of this organism. 

PMID- 25071773
TI  - Complement activation and regulation in preeclamptic placenta.
AB  - Preeclampsia (PE) is a common disorder of pregnancy originating in the placenta.
      We examined whether excessive activation or poor regulation of the complement
      system at the maternal-fetal interface could contribute to the development of PE.
      Location and occurrence of complement components and regulators in placentae were
      analyzed. Cryostat sections of placentae were processed from 7 early-onset PE
      (diagnosis <34 weeks of gestation), 5 late-onset PE, 10 control pregnancies, and
      immunostained for 6 complement activators and 6 inhibitors. Fluorescence was
      quantified and compared between PE and control placentae. Gene copy numbers of
      complement components C4A and C4B were assessed by a quantitative PCR method.
      Maternal C4 deficiencies (>=1 missing or non-functional C4) were most common in
      the early-onset PE group (71%), and more frequent in late-onset PE compared to
      healthy controls (60 vs. 38%). Complement C1q deposition differed significantly
      between control and patient groups: controls and early-onset PE patients had more
      C1q than late-onset PE patients (mean p = 0.01 and p = 0.005, respectively). C3
      activation was analyzed by staining for C3b/iC3b and C3d. C3d was mostly specific
      to the basal syncytium and C3b/iC3b diffuse in other structures, but there were
      no clear differences between the study groups. Activated C4 and membrane-bound
      regulators CD55, CD46, and CD59 were observed abundantly in the
      syncytiotrophoblast. Syncytial knots, structures enriched in PE, stained
      specifically for the classical pathway inhibitor C4bp, whereas the key regulator
      alternative pathway, factor H (FH) showed a wider distribution in the placenta.
      Differences in C1q deposition between late- and early-onset PE groups may be
      indicative of the different etiology of PE symptoms in these patients. Irregular
      distribution of the complement regulators C4bp and FH in the PE placenta and a
      higher frequency of C4A deficiencies suggest a disturbed balance between
      complement activation and regulation in PE. 

PMID- 25071774
TI  - Toll-like receptor 4 in inflammation and angiogenesis: a double-edged sword.

PMID- 25071771
TI  - The Cross-Talk between Spirochetal Lipoproteins and Immunity.
AB  - Spirochetal diseases such as syphilis, Lyme disease, and leptospirosis are major
      threats to public health. However, the immunopathogenesis of these diseases has
      not been fully elucidated. Spirochetes interact with the host through various
      structural components such as lipopolysaccharides (LPS), surface lipoproteins,
      and glycolipids. Although spirochetal antigens such as LPS and glycolipids may
      contribute to the inflammatory response during spirochetal infections,
      spirochetes such as Treponema pallidum and Borrelia burgdorferi lack LPS.
      Lipoproteins are most abundant proteins that are expressed in all spirochetes and
      often determine how spirochetes interact with their environment. Lipoproteins are
      pro-inflammatory, may regulate responses from both innate and adaptive immunity
      and enable the spirochetes to adhere to the host or the tick midgut or to evade
      the immune system. However, most of the spirochetal lipoproteins have unknown
      function. Herein, the immunomodulatory effects of spirochetal lipoproteins are
      reviewed and are grouped into two main categories: effects related to immune
      evasion and effects related to immune activation. Understanding lipoprotein
      induced immunomodulation will aid in elucidating innate immunopathogenesis
      processes and subsequent adaptive mechanisms potentially relevant to spirochetal
      disease vaccine development and to inflammatory events associated with
      spirochetal diseases. 

PMID- 25071775
TI  - Distinct functional programs in fetal T and myeloid lineages.

PMID- 25071776
TI  - Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL
      1R2 and IL-1RA.
AB  - OBJECTIVE: Weight-loss is a near societal obsession and many diet programs use
      significant calorie restriction including fasting/short term starvation to
      generate rapid effects. Fasting is also a well-recognized cause of
      immunosuppression especially within the innate immune system. In this study, we
      sought to determine if the IL-1 arm of the neuroimmune system was down-regulated
      by a 24 h fast and how fasting might generate this effect. DESIGN: Mice were
      allowed ad libitum access to food or had food withheld for 24 h. Expression of
      the endogenous IL-1 antagonists, IL-1 receptor type 2 (IL-1R2), and IL-1 receptor
      antagonist (IL-1RA) was determined as were sickness behaviors before and after IL
      1beta administration. RESULTS: Fasting markedly increased gene expression of IL
      1R2 (83-fold in adipose tissue, 9.5-fold in liver) and IL-1RA (68-fold in liver).
      Fasted mice were protected from IL-1beta-induced weight-loss, hypoglycemia, loss
      of locomotor, and social anxiety. These protections were coupled to a large
      positive interaction of fasting and IL-1beta on IL-1R2 gene expression in adipose
      tissue and liver (2.6- and 1.6-fold, respectively). Fasting not only increased IL
      1RA and IL-1R2 protein 2.5- and 3.2-fold, respectively, in liver but also
      increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4
      fold increase in plasma free-fatty acids (FFAs) and a 2.1-fold increase in plasma
      corticosterone. Inhibition, of glucocorticoid action with mifepristone did not
      impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the
      FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14-
      and 11-fold, respectively. CONCLUSION: These findings indicate that fasting
      augments expression of endogenous IL-1 antagonists inducing IL-1 resistance.
      Fasting-induced increases in plasma FFAs appears to be a signal that drives
      immunosuppression during fasting/short term starvation.

PMID- 25071777
TI  - A comparative review of toll-like receptor 4 expression and functionality in
      different animal species.
AB  - Toll-like receptors (TLRs) belong to the pattern recognition receptor (PRR)
      family, a key component of the innate immune system. TLRs detect invading
      pathogens and initiate an immediate immune response to them, followed by a long
      lasting adaptive immune response. Activation of TLRs leads to the synthesis of
      pro-inflammatory cytokines and chemokines and the expression of co-stimulatory
      molecules. TLR4 specifically recognizes bacterial lipopolysaccharide, along with
      several other components of pathogens and endogenous molecules produced during
      abnormal situations, such as tissue damage. Evolution across species can lead to
      substantial diversity in the TLR4's affinity and specificity to its ligands, the
      TLR4 gene and cellular expression patterns and tissue distribution. Consequently,
      TLR4 functions vary across different species. In recent years, the use of
      synthetic TLR agonists as adjuvants has emerged as a realistic therapeutic goal,
      notably for the development of vaccines against poorly immunogenic targets. Given
      that an adjuvanted vaccine must be assessed in pre-clinical animal models before
      being tested in humans, the extent to which an animal model represents and
      predicts the human condition is of particular importance. This review focuses on
      the current knowledge on the critical points of divergence between human and the
      mammalian species commonly used in vaccine research and development (non-human
      primate, mouse, rat, rabbit, swine, and dog), in terms of molecular, cellular,
      and functional properties of TLR4. 

PMID- 25071778
TI  - The dual role of nod-like receptors in mucosal innate immunity and chronic
      intestinal inflammation.
AB  - Nucleotide-binding and oligomerization domain NOD-like receptors (NLRs) are
      highly conserved cytosolic pattern recognition receptors that play, in
      combination with toll-like receptors, a critical role in innate immunity and
      inflammation. These proteins are characterized by a central oligomerization
      domain termed nucleotide-binding domain, and a protein interaction domain
      containing leucine-rich repeats. Some NLRs, including NOD1 and NOD2, sense the
      cytosolic presence of conserved bacterial molecular signatures and drive the
      activation of mitogen-activated protein kinase and the transcription factor NF
      kappaB. A different set of NLRs induces caspase-1 activation through the assembly
      of large protein complexes known as inflammasomes. Activation of NLR proteins
      results in secretion of pro-inflammatory cytokines and subsequent inflammatory
      responses. The critical role of NLRs in innate immunity is underscored by the
      fact that polymorphisms within their genes are implicated in the development of
      several immune-mediated diseases, including inflammatory bowel disease. Over the
      past few years, the role of NLRs in intestinal homeostasis has been highlighted,
      however the mechanism by which dysfunction in these proteins leads to aberrant
      inflammation is still the focus of much investigation. The purpose of this review
      is to systematically evaluate the function of NLRs in mucosal innate immunity and
      understand how genetic or functional alterations in these components can lead to
      the disruption of intestinal homeostasis, and the subsequent development of
      chronic inflammation. 

PMID- 25071779
TI  - The Role of Non-Cognate T Cell Stimulation during Intracellular Bacterial
      Infection.
AB  - Intra-macrophage bacterial infections cause significant morbidity and mortality
      in both the developed and developing world. Protective host immune responses to
      these infections initially requires the activation and expansion of pathogen
      specific CD4 Th1 cells within lymphoid tissues and subsequent relocation of these
      effector cells to sites of infection. After entering infected tissues, the
      elicitation of Th1 bactericidal activity can be triggered by cognate or non
      cognate signals that are delivered by locally infected antigen-presenting cells
      and innate cells. However, the contribution of non-cognate stimulation to the
      resolution of bacterial infection remains poorly understood, especially in the
      context of a Th1 response. Here, we review the current data on Th1 cell
      activation and expansion in mouse models of Salmonella and Chlamydia infection
      and discuss the potential role of non-cognate Th1 cell stimulation in these
      disease models. Greater understanding of this pathway of T cell activation may
      lead to the design of therapeutics or vaccines to combat intra-macrophage
      pathogens. 

PMID- 25071780
TI  - Every breath you take: the impact of environment on resident memory CD8 T cells
      in the lung.
AB  - Resident memory T cells (TRM) are broadly defined as a population of T cells,
      which persist in non-lymphoid sites long-term, do not re-enter the circulation,
      and are distinct from central memory T cells (TCM) and circulating effector
      memory T cells (TEM). Recent studies have described populations of TRM cells in
      the skin, gut, lungs, and nervous tissue. However, it is becoming increasingly
      clear that the specific environment in which the TRM reside can further refine
      their phenotypical and functional properties. Here, we focus on the TRM cells
      that develop following respiratory infection and reside in the lungs and the lung
      airways. Specifically, we will review recent studies that have described some of
      the requirements for establishment of TRM cells in these tissues, and the
      defining characteristics of TRM in the lungs and lung airways. With continual
      bombardment of the respiratory tract by both pathogenic and environmental
      antigens, dynamic fluctuations in the local milieu including homeostatic
      resources and niche restrictions can impact TRM longevity. Beyond a comprehensive
      characterization of lung TRM cells, special attention will be placed on studies,
      which have defined how the microenvironment of the lung influences memory T cell
      survival at this site. As memory T cell populations in the lung airways are
      requisite for protection yet wane numerically over time, developing a
      comprehensive picture of factors which may influence TRM development and
      persistence at these sites is important for improving T cell-based vaccine
      design. 

PMID- 25071781
TI  - The Immunodominant T-Cell Epitopes of the Mycolyl-Transferases of the Antigen 85
      Complex of M. tuberculosis.
AB  - The Ag85 complex is a 30-32 kDa family of three proteins (Ag85A, Ag85B, and
      Ag85C), which all three possess enzymatic mycolyl-transferase activity involved
      in the coupling of mycolic acids to the arabinogalactan of the cell wall and in
      the biogenesis of cord factor. By virtue of their strong potential to induce Th1
      type immune responses, important for the control of intracellular infections,
      members of the Ag85 family rank among the most promising TB vaccine candidate
      antigens. Ag85A and Ag85B, initially purified from Mycobacterium bovis bacillus
      Calmette-Guerin (BCG)/Mycobacterium tuberculosis culture filtrate respectively,
      induce strong T-cell proliferation and IFN-gamma production in most healthy
      individuals latently infected with M. tuberculosis and in BCG-vaccinated mice and
      humans but not in tuberculosis patients. Members of the Ag85 complex are highly
      conserved in other mycobacterial species. Mice and humans infected with
      Mycobacterium ulcerans or cattle infected with M. bovis or Mycobacterium avium
      subsp. paratuberculosis also show strong T-cell responses to this protein family.
      Using synthetic overlapping peptides, bio-informatic prediction programs and
      tetramer-binding studies, a number of immunodominant CD4(+) and CD8(+) T-cell
      epitopes have been identified in experimental animal models as well as in humans,
      using proliferation and Th1 cytokine secretion as main read-outs. The results
      from these studies are summarized in this review. 

PMID- 25071782
TI  - A High-Content RNAi Screen Identifies Ubiquitin Modifiers That Regulate TNF
      Dependent Nuclear Accumulation of NF-kappaB.
AB  - The mammalian tumor necrosis factor (TNF) cytokine is a central mediator of
      inflammatory events. Recent studies revealed a number of complex and
      sophisticated interactions between the TNF pathway and the enzymatic activities
      encoded by ubiquitin ligases and deubiquitylation enzymes. However, very little
      is known about the identity of the ubiquitin pathway members that control the
      extent of ubiquitylation in TNF responses. To address this deficit, we conducted
      an unbiased, high-content screen of the human ubiquitin pathway for gene products
      that control defining features of the cellular response to TNF. In particular, we
      sought to identify ubiquitin modifying enzymes that alter the ability of TNF to
      regulate the nuclear accumulation of nuclear factor kappa B. In this screen, we
      identified and validated several novel regulators of the TNF pathway. We believe
      these regulators constitute potential targets for pharmacological interventions
      that manipulate TNF-dependent inflammation. 

PMID- 25071783
TI  - Computational and experimental prediction of human C-type lectin receptor
      druggability.
AB  - Mammalian C-type lectin receptors (CTLRS) are involved in many aspects of immune
      cell regulation such as pathogen recognition, clearance of apoptotic bodies, and
      lymphocyte homing. Despite a great interest in modulating CTLR recognition of
      carbohydrates, the number of specific molecular probes is limited. To this end,
      we predicted the druggability of a panel of 22 CTLRs using DoGSiteScorer. The
      computed druggability scores of most structures were low, characterizing this
      family as either challenging or even undruggable. To further explore these
      findings, we employed a fluorine-based nuclear magnetic resonance screening of
      fragment mixtures against DC-SIGN, a receptor of pharmacological interest. To our
      surprise, we found many fragment hits associated with the carbohydrate
      recognition site (hit rate = 13.5%). A surface plasmon resonance-based follow-up
      assay confirmed 18 of these fragments (47%) and equilibrium dissociation
      constants were determined. Encouraged by these findings we expanded our
      experimental druggability prediction to Langerin and MCL and found medium to high
      hit rates as well, being 15.7 and 10.0%, respectively. Our results highlight
      limitations of current in silico approaches to druggability assessment, in
      particular, with regard to carbohydrate-binding proteins. In sum, our data
      indicate that small molecule ligands for a larger panel of CTLRs can be
      developed. 

PMID- 25071784
TI  - Communication between Human Dendritic Cell Subsets in Tuberculosis: Requirements
      for Naive CD4(+) T Cell Stimulation.
AB  - Human primary dendritic cells (DCs) are heterogeneous by phenotype, function, and
      tissue localization and distinct from inflammatory monocyte-derived DCs. Current
      information regarding the susceptibility and functional role of primary human DC
      subsets to Mycobacterium tuberculosis (Mtb) infection is limited. Here, we
      dissect the response of different primary DC subsets to Mtb infection. Myeloid
      CD11c(+) cells and pDCs (C-type lectin 4C(+) cells) were located in human lymph
      nodes (LNs) of tuberculosis (TB) patients by histochemistry. Rare CD141(hi) DCs
      (C-type lectin 9A(+) cells) were also identified. Infection with live Mtb
      revealed a higher responsiveness of myeloid CD1c(+) DCs compared to CD141(hi) DCs
      and pDCs. CD1c(+) DCs produced interleukin (IL)-6, tumor necrosis factor alpha,
      and IL-1beta but not IL-12p70, a cytokine important for Th1 activation and host
      defenses against Mtb. Yet, CD1c(+) DCs were able to activate autologous naive
      CD4(+) T cells. By combining cell purification with fluorescence-activated cell
      sorting and gene expression profiling on rare cell populations, we detected in
      responding CD4(+) T cells, genes related to effector-cytolytic functions and
      transcription factors associated with Th1, Th17, and Treg polarization,
      suggesting multifunctional properties in our experimental conditions. Finally,
      immunohistologic analyses revealed contact between CD11c(+) cells and pDCs in LNs
      of TB patients and in vitro data suggest that cooperation between Mtb-infected
      CD1c(+) DCs and pDCs favors stimulation of CD4(+) T cells. 

PMID- 25071786
TI  - More Surprises in the Development of an HIV Vaccine.

PMID- 25071788
TI  - Differential secretome analysis of Pseudomonas syringae pv tomato using gel-free
      MS proteomics.
AB  - The plant pathogen Pseudomonas syringae pv.tomato (DC3000) causes virulence by
      delivering effector proteins into host plant cells through its type three
      secretion system (T3SS). In response to the plant environment DC3000 expresses
      hypersensitive response and pathogenicity genes (hrp). Pathogenesis depends on
      the ability of the pathogen to manipulate the plant metabolism and to inhibit
      plant immunity, which depends to a large degree on the plant's capacity to
      recognize both pathogen and microbial determinants (PAMP/MAMP-triggered
      immunity). We have developed and employed MS-based shotgun and targeted
      proteomics to (i) elucidate the extracellular and secretome composition of DC3000
      and (ii) evaluate temporal features of the assembly of the T3SS and the secretion
      process together with its dependence of pH. The proteomic screen, under hrp
      inducing in vitro conditions, of extracellular and cytoplasmatic fractions
      indicated the segregated presence of not only T3SS implicated proteins such as
      HopP1, HrpK1, HrpA1 and AvrPto1, but also of proteins not usually associated with
      the T3SS or with pathogenicity. Using multiple reaction monitoring MS (MRM-MS) to
      quantify HrpA1 and AvrPto1, we found that HrpA1 is rapidly expressed, at a strict
      pH-dependent rate and is post-translationally processed extracellularly. These
      features appear to not interfere with rapid AvrPto1 expression and secretion but
      may suggest some temporal post-translational regulatory mechanism of the T3SS
      assembly. The high specificity and sensitivity of the MRM-MS approach should
      provide a powerful tool to measure secretion and translocation in infected
      tissues. 

PMID- 25071787
TI  - Mucosal resident memory CD4 T cells in protection and immunopathology.
AB  - Tissue-resident memory T cells (TRM) comprise a newly defined subset, which
      comprises a major component of lymphocyte populations in diverse peripheral
      tissue sites, including mucosal tissues, barrier surfaces, and in other non
      lymphoid and lymphoid sites in humans and mice. Many studies have focused on the
      role of CD8 TRM in protection; however, there is now accumulating evidence that
      CD4 TRM predominate in tissue sites, and are integral for in situ protective
      immunity, particularly in mucosal sites. New evidence suggests that mucosal CD4
      TRM populations differentiate at tissue sites following the recruitment of
      effector T cells by local inflammation or infection. The resulting TRM
      populations are enriched in T-cell specificities associated with the inducing
      pathogen/antigen. This compartmentalization of memory T cells at specific tissue
      sites may provide an optimal design for future vaccination strategies. In
      addition, emerging evidence suggests that CD4 TRM may also play a role in
      immunoregulation and immunopathology, and therefore, targeting TRM may be a
      viable therapeutic approach to treat inflammatory diseases in mucosal sites. This
      review will summarize our current understanding of CD4 TRM in diverse tissues,
      with an emphasis on their role in protective immunity and the mechanisms by which
      these populations are established and maintained in diverse mucosal sites. 

PMID- 25071789
TI  - Hydrogen peroxide-independent generation of superoxide by plant peroxidase:
      hypotheses and supportive data employing ferrous ion as a model stimulus.
AB  - When plants are threaten by microbial attacks or treated with elicitors,
      alkalization of extracellular space is often induced and thus pH-dependent
      extracellular peroxidase-mediated oxidative burst reportedly takes place,
      especially at the site of microbial challenge. However, direct stimulus involved
      in activation of peroxidase-catalyzed oxidative burst has not been identified to
      date. Here, we would like to propose a likely role for free ferrous ion in
      reduction of ferric native peroxidase into ferrous enzyme intermediate which
      readily produces superoxide anion via mechanism involving Compound III,
      especially under alkaline condition, thus, possibly contributing to the plant
      defense mechanism. Through spectroscopic and chemiluminescence (CL) analyses of
      reactions catalyzed by horseradish peroxidase (HRP), the present study proposed
      that plant peroxidase-catalyzed production of superoxide anion can be stimulated
      in the absence of conventional peroxidase substrates but in the presence of free
      ferrous ion. 

PMID- 25071785
TI  - NOD-Like Receptors: Master Regulators of Inflammation and Cancer.
AB  - Cytosolic NOD-like receptors (NLRs) have been associated with human diseases
      including infections, cancer, and autoimmune and inflammatory disorders. These
      innate immune pattern recognition molecules are essential for controlling
      inflammatory mechanisms through induction of cytokines, chemokines, and anti
      microbial genes. Upon activation, some NLRs form multi-protein complexes called
      inflammasomes, while others orchestrate caspase-independent nuclear factor kappa
      B (NF-kappaB) and mitogen activated protein kinase (MAPK) signaling. Moreover,
      NLRs and their downstream signaling components engage in an intricate crosstalk
      with cell death and autophagy pathways, both critical processes for cancer
      development. Recently, increasing evidence has extended the concept that chronic
      inflammation caused by abberant NLR signaling is a powerful driver of
      carcinogenesis, where it abets genetic mutations, tumor growth, and progression.
      In this review, we explore the rapidly expanding area of research regarding the
      expression and functions of NLRs in different types of cancers. Furthermore, we
      particularly focus on how maintaining tissue homeostasis and regulating tissue
      repair may provide a logical platform for understanding the liaisons between the
      NLR-driven inflammatory responses and cancer. Finally, we outline novel
      therapeutic approaches that target NLR signaling and speculate how these could be
      developed as potential pharmaceutical alternatives for cancer treatment. 

PMID- 25071790
TI  - Photosynthesis in a different light: spectro-microscopy for in vivo
      characterization of chloroplasts.
AB  - During photosynthesis, energy conversion at the two photosystems is controlled by
      highly complex and dynamic adaptation processes triggered by external factors
      such as light quality, intensity, and duration, or internal cues such as carbon
      availability. These dynamics have remained largely concealed so far, because
      current analytical techniques are based on the investigation of isolated
      chloroplasts lacking full adaptation ability and are performed at non
      physiologically low temperatures. Here, we use non-invasive in planta spectro
      microscopic approaches to investigate living chloroplasts in their native
      environment at ambient temperatures. This is a valuable approach to study the
      complex function of these systems, because an intrinsic property-the fluorescence
      emission-is exploited and no additional external perturbations are introduced.
      Our analysis demonstrates a dynamic adjustment of not only the
      photosystemI/photosystemII (PSI/PSII) intensity ratio in the chloroplasts but
      also of the capacity of the LHCs for energy transfer in response to environmental
      and internal cues. 

PMID- 25071792
TI  - Revealing changes in molecular composition of plant cell walls on the micron
      level by Raman mapping and vertex component analysis (VCA).
AB  - At the molecular level the plant cell walls consist of a few nanometer thick semi
      crystalline cellulose fibrils embedded in amorphous matrix polymers such as
      pectins, hemicelluloses, and lignins. The arrangement of these molecules within
      the cell wall in different plant tissues, cells and cell wall layers is of
      crucial importance for a better understanding and thus optimized utilization of
      plant biomass. During the last years Confocal Raman microscopy evolved as a
      powerful method in plant science by revealing the different molecules in context
      with the microstructure. In this study two-dimensional spectral maps have been
      acquired of micro-cross-sections of spruce (softwood) and beech (hardwood). Raman
      images have been derived by using univariate (band integration, height ratios)
      and multivariate methods [vertex component analysis (VCA)]. While univariate
      analysis only visualizes changes in selected band heights or areas, VCA separates
      anatomical regions and cell wall layers with the most different molecular
      structures. Beside visualization of the distinguished regions and features the
      underlying molecular structure can be derived based on the endmember spectra. VCA
      revealed that the lumen sided S3 layer has a similar molecular composition as the
      pit membrane, both revealing a clear change in lignin composition compared to all
      other cell wall regions. Within the S2 layer a lamellar structure was visualized,
      which was elucidated to derive from slight changes in lignin composition and
      content and might be due to successive but not uniform lignification during
      growth. 

PMID- 25071791
TI  - Fourier transform mid infrared spectroscopy applications for monitoring the
      structural plasticity of plant cell walls.
AB  - Fourier transform mid-infrared (FT-MIR) spectroscopy has been extensively used as
      a potent, fast and non-destructive procedure for analyzing cell wall
      architectures, with the capacity to provide abundant information about their
      polymers, functional groups, and in muro entanglement. In conjunction with
      multivariate analyses, this method has proved to be a valuable tool for tracking
      alterations in cell walls. The present review examines recent progress in the use
      of FT-MIR spectroscopy to monitor cell wall changes occurring in muro as a result
      of various factors, such as growth and development processes, genetic
      modifications, exposition or habituation to cellulose biosynthesis inhibitors and
      responses to other abiotic or biotic stresses, as well as its biotechnological
      applications. 

PMID- 25071793
TI  - Direct reprogramming of adult somatic cells toward adventitious root formation in
      forest tree species: the effect of the juvenile-adult transition.
AB  - Cellular plasticity refers, among others, to the capability of differentiated
      cells to switch the differentiation process and acquire new fates. One way by
      which plant cell plasticity is manifested is through de novo regeneration of
      organs from somatic differentiated cells in an ectopic location. However,
      switching the developmental program of adult cells prior to organ regeneration is
      difficult in many plant species, especially in forest tree species. In these
      species, a decline in the capacity to regenerate shoots, roots, or embryos from
      somatic differentiated cells is associated with tree age and maturation. The
      decline in the ability to form adventitious roots from stem cuttings is one of
      the most dramatic effects of maturation, and has been the subject of
      investigations on the basic nature of the process. Cell fate switches, both in
      plants and animals, are characterized by remarkable changes in the pattern of
      gene expression, as cells switch from the characteristic expression pattern of a
      somatic cell to a new one directing a new developmental pathway. Therefore,
      determining the way by which cells reset their gene expression pattern is crucial
      to understand cellular plasticity. The presence of specific cellular signaling
      pathways or tissue-specific factors underlying the establishment, maintenance,
      and redirection of gene expression patterns in the tissues involved in
      adventitious root formation could be crucial for cell fate switch and for the
      control of age-dependent cellular plasticity. 

PMID- 25071794
TI  - Maturation processes and structures of small secreted peptides in plants.
AB  - In the past decade, small secreted peptides have proven to be essential for
      various aspects of plant growth and development, including the maintenance of
      certain stem cell populations. Most small secreted peptides identified in plants
      to date are recognized by membrane-localized receptor kinases, the largest family
      of receptor proteins in the plant genome. This peptide-receptor interaction is
      essential for initiating intracellular signaling cascades. Small secreted
      peptides often undergo post-translational modifications and proteolytic
      processing to generate the mature peptides. Recent studies suggest that, in
      contrast to the situation in mammals, the proteolytic processing of plant
      peptides involves a number of complex steps. Furthermore, NMR-based structural
      analysis demonstrated that post-translational modifications induce the
      conformational changes needed for full activity. In this mini review, we
      summarize recent advances in our understanding of how small secreted peptides are
      modified and processed into biologically active peptides and describe the mature
      structures of small secreted peptides in plants. 

PMID- 25071795
TI  - Getting to the edge: protein dynamical networks as a new frontier in plant
      microbe interactions.
AB  - A systems perspective on diverse phenotypes, mechanisms of infection, and
      responses to environmental stresses can lead to considerable advances in
      agriculture and medicine. A significant promise of systems biology within plants
      is the development of disease-resistant crop varieties, which would maximize
      yield output for food, clothing, building materials, and biofuel production. A
      systems or "-omics" perspective frames the next frontier in the search for
      enhanced knowledge of plant network biology. The functional understanding of
      network structure and dynamics is vital to expanding our knowledge of how the
      intercellular communication processes are executed. This review article will
      systematically discuss various levels of organization of systems biology
      beginning with the building blocks termed "-omes" and ending with complex
      transcriptional and protein-protein interaction networks. We will also highlight
      the prevailing computational modeling approaches of biological regulatory network
      dynamics. The latest developments in the "-omics" approach will be reviewed and
      discussed to underline and highlight novel technologies and research directions
      in plant network biology. 

PMID- 25071796
TI  - Sugars take a central position in plant growth, development and, stress
      responses. A focus on apical dominance.

PMID- 25071797
TI  - A dynamic meiotic SUN belt includes the zygotene-stage telomere bouquet and is
      disrupted in chromosome segregation mutants of maize (Zea mays L.).
AB  - The nuclear envelope (NE) plays an essential role in meiotic telomere behavior
      and links the cytoplasm and nucleoplasm during homologous chromosome pairing and
      recombination in many eukaryotic species. Resident NE proteins including SUN (Sad
      1/UNC-84) and KASH (Klarsicht/ANC-1/Syne-homology) domain proteins are known to
      interact forming the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex
      that connects chromatin to the cytoskeleton. To investigate the possible cross
      kingdom conservation of SUN protein functions in plant meiosis, we
      immunolocalized maize SUN2 using 3D microscopy of pollen mother cells from maize
      (Zea mays L.), a large-genome plant model with a canonical NE zygotene-stage
      telomere bouquet. We detected SUN2 at the nuclear periphery and found that it
      exhibited a distinct belt-like structure that transitioned to a half-belt during
      the zygotene stage and back to a full belt during and beyond the pachytene stage.
      The zygotene-stage half-belt SUN structure was shown by 3D immuno-FISH to include
      the NE-associated telomere cluster that defines the bouquet stage and coincides
      with homologous chromosome synapsis. Microtubule and filamentous actin staining
      patterns did not show any obvious belt or a retracted-like structure other than a
      general enrichment of tubulin staining distributed widely around the nucleus and
      throughout the cytoplasm. Genetic disruption of the meiotic SUN belt staining
      patterns with three different meiosis-specific mutants, desynaptic (dy1),
      asynaptic1 (as1), and divergent spindle1 (dv1) provides additional evidence for
      the role of the nuclear envelope in meiotic chromosome behavior. Taking into
      account all of the observations from this study, we propose that the maize SUN
      belt is directly or indirectly involved in meiotic telomere dynamics, chromosome
      synapsis, and possibly integration of signals and forces across the meiotic
      prophase nuclear envelope. 

PMID- 25071798
TI  - Regulation of xylem cell fate.
AB  - The vascular system is organized throughout the plant body for transporting
      water, nutrients, and signaling molecules. During vascular development, xylem,
      phloem, and procambial/cambial cells are produced in a spatiotemporally organized
      manner. Several key regulators for xylem cell patterning and differentiation have
      been discovered, including auxin, cytokinin, CLE peptides, microRNAs, HD-ZIPIIIs,
      VNDs, and moving transcription factors SHR and AHLs. Recent studies are
      identifying functional interactions among these factors that ultimately determine
      xylem cell fate. This review focuses on regulatory networks underlying xylem cell
      fate determination in root vascular development. 

PMID- 25071799
TI  - Nuclear-encoded factors associated with the chloroplast transcription machinery
      of higher plants.
AB  - Plastid transcription is crucial for plant growth and development. There exist
      two types of RNA polymerases in plastids: a nuclear-encoded RNA polymerase (NEP)
      and plastid-encoded RNA polymerase (PEP). PEP is the major RNA polymerase
      activity in chloroplast. Its core subunits are encoded by the plastid genome, and
      these are embedded into a larger complex of nuclear-encoded subunits. Biochemical
      and genetics analysis identified at least 12 proteins are tightly associated with
      the core subunit, while about 34 further proteins are associated more loosely
      generating larger complexes such as the transcriptionally active chromosome (TAC)
      or a part of the nucleoid. Domain analyses and functional investigations
      suggested that these nuclear-encoded factors may form several functional modules
      that mediate regulation of plastid gene expression by light, redox,
      phosphorylation, and heat stress. Genetic analyses also identified that some
      nuclear-encoded proteins in the chloroplast that are important for plastid gene
      expression, although a physical association with the transcriptional machinery is
      not observed. This covers several PPR proteins including CLB19, PDM1/SEL1, OTP70,
      and YS1 which are involved in the processing of transcripts for PEP core subunit
      as well as AtECB2, Prin2, SVR4-Like, and NARA5 that are also important for
      plastid gene expression, although their functions are unclear. 

PMID- 25071800
TI  - Nitrate reductase (15)N discrimination in Arabidopsis thaliana, Zea mays,
      Aspergillus niger, Pichea angusta, and Escherichia coli.
AB  - Stable (15)N isotopes have been used to examine movement of nitrogen (N) through
      various pools of the global N cycle. A central reaction in the cycle involves the
      reduction of nitrate (NO(-) 3) to nitrite (NO(-) 2) catalyzed by nitrate
      reductase (NR). Discrimination against (15)N by NR is a major determinant of
      isotopic differences among N pools. Here, we measured in vitro (15)N
      discrimination by several NRs purified from plants, fungi, and a bacterium to
      determine the intrinsic (15)N discrimination by the enzyme and to evaluate the
      validity of measurements made using (15)N-enriched NO(-) 3. Observed NR isotope
      discrimination ranged from 22 to 320/00 (kinetic isotope effects of 1.022-1.032)
      among the different isozymes at natural abundance (15)N (0.37%). As the
      fractional (15)N content of substrate NO(-) 3 increased from natural abundance,
      the product (15)N fraction deviated significantly from that expected based on
      substrate enrichment and (15)N discrimination measured at natural abundance.
      Additionally, isotopic discrimination by denitrifying bacteria used to reduce NO(
      ) 3 and NO(-) 2 in some protocols became a greater source of error as (15)N
      enrichment increased. We briefly discuss potential causes of the experimental
      artifacts with enriched (15)N and recommend against the use of highly enriched
      (15)N tracers to study N discrimination in plants or soils. 

PMID- 25071801
TI  - Conventional and phenomics characterization provides insight into the diversity
      and relationships of hypervariable scarlet (Solanum aethiopicum L.) and gboma (S.
      macrocarpon L.) eggplant complexes.
AB  - Scarlet (Solanum aethiopicum) and gboma (S. macrocarpon) eggplants are major
      vegetable crops in sub-Saharan Africa. Together with their respective wild
      ancestors (S. anguivi and S. dasyphyllum) and intermediate cultivated-wild forms
      they constitute the so-called scarlet and gboma eggplant complexes. We used
      conventional descriptors and the high-throughput phenomics tool Tomato Analyzer
      for characterizing 63 accessions of the scarlet eggplant complex, including the
      four S. aethiopicum cultivar groups (Aculeatum, Gilo, Kumba, and Shum),
      Intermediate S. aethiopicum-S. anguivi forms, and S. anguivi, and 12 cultivated
      and wild accessions of the gboma eggplant complex. A large diversity was found
      between both complexes, showing that they are very well differentiated from each
      other. Within the scarlet eggplant complex, many significant differences were
      also found among cultivar groups, but more differences were found for fruit
      traits evaluated with Tomato Analyzer than with conventional descriptors. In
      particular, Tomato Analyzer phenomics characterization was useful for
      distinguishing small fruited groups (Shum, Intermediate, and S. anguivi), as well
      as groups for which few or no significant differences were observed for plant
      traits. Multivariate principal components analysis (PCA) separated well all
      groups, except the Intermediate group which plotted between S. anguivi and small
      fruited S. aethiopicum accessions. For the gboma eggplant complex, S. dasyphyllum
      was clearly distinguished from S. macrocarpon and an important diversity was
      found in the latter. The results have shown that both complexes are hypervariable
      and have provided insight into their diversity and relationships. The information
      obtained has important implications for the conservation and management of
      genetic resources as well as for the selection and breeding of both scarlet and
      gboma eggplants. 

PMID- 25071802
TI  - Plant polyamines in stress and development: an emerging area of research in plant
      sciences.

PMID- 25071803
TI  - Molecular basis of natural variation and environmental control of trichome
      patterning.
AB  - Trichomes are differentiated epidermal cells on above ground organs of nearly all
      land plants. They play important protective roles as structural defenses upon
      biotic attacks such as herbivory, oviposition and fungal infections, and against
      abiotic stressors such as drought, heat, freezing, excess of light, and UV
      radiation. The pattern and density of trichomes is highly variable within natural
      population suggesting tradeoffs between traits positively affecting fitness such
      as resistance and the costs of trichome production. The spatial distribution of
      trichomes is regulated through a combination of endogenous developmental programs
      and external signals. This review summarizes the current understanding on the
      molecular basis of the natural variation and the role of phytohormones and
      environmental stimuli on trichome patterning. 

PMID- 25071804
TI  - Host and viral RNA-binding proteins involved in membrane targeting, replication
      and intercellular movement of plant RNA virus genomes.
AB  - Many plant viruses have positive-strand RNA [(+)RNA] as their genome. Therefore,
      it is not surprising that RNA-binding proteins (RBPs) play important roles during
      (+)RNA virus infection in host plants. Increasing evidence demonstrates that
      viral and host RBPs play critical roles in multiple steps of the viral life
      cycle, including translation and replication of viral genomic RNAs, and their
      intra- and intercellular movement. Although studies focusing on the RNA-binding
      activities of viral and host proteins, and their associations with membrane
      targeting, and intercellular movement of viral genomes have been limited to a few
      viruses, these studies have provided important insights into the molecular
      mechanisms underlying the replication and movement of viral genomic RNAs. In this
      review, we briefly overview the currently defined roles of viral and host RBPs
      whose RNA-binding activity have been confirmed experimentally in association with
      their membrane targeting, and intercellular movement of plant RNA virus genomes. 

PMID- 25071805
TI  - Agrobacterium tumefaciens responses to plant-derived signaling molecules.
AB  - As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of
      plant hosts and causes plant tumors also known as crown galls. The complexity of
      Agrobacterium-plant interaction has been studied for several decades.
      Agrobacterium pathogenicity is largely attributed to its evolved capabilities of
      precise recognition and response to plant-derived chemical signals. Agrobacterium
      perceives plant-derived signals to activate its virulence genes, which are
      responsible for transferring and integrating its Transferred DNA (T-DNA) from its
      Tumor-inducing (Ti) plasmid into the plant nucleus. The expression of T-DNA in
      plant hosts leads to the production of a large amount of indole-3-acetic acid
      (IAA), cytokinin (CK), and opines. IAA and CK stimulate plant growth, resulting
      in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as
      signals in order to activate its quorum sensing (QS) to further promote virulence
      and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived
      signals including gamma-amino butyric acid and salicylic acid (SA) to activate
      quorum quenching that reduces the level of QS signals, thereby avoiding the
      elicitation of plant defense and preserving energy. In addition, Agrobacterium
      hijacks plant-derived signals including SA, IAA, and ethylene to down-regulate
      its virulence genes located on the Ti plasmid. Moreover, certain metabolites from
      corn (Zea mays) also inhibit the expression of Agrobacterium virulence genes.
      Here we outline the responses of Agrobacterium to major plant-derived signals
      that impact Agrobacterium-plant interactions. 

PMID- 25071806
TI  - Virus-induced gene silencing is a versatile tool for unraveling the functional
      relevance of multiple abiotic-stress-responsive genes in crop plants.
AB  - Virus-induced gene silencing (VIGS) is an effective tool for gene function
      analysis in plants. Over the last decade, VIGS has been successfully used as both
      a forward and reverse genetics technique for gene function analysis in various
      model plants, as well as crop plants. With the increased identification of
      differentially expressed genes under various abiotic stresses through high
      throughput transcript profiling, the application of VIGS is expected to be
      important in the future for functional characterization of a large number of
      genes. In the recent past, VIGS was proven to be an elegant tool for functional
      characterization of genes associated with abiotic stress responses. In this
      review, we provide an overview of how VIGS is used in different crop species to
      characterize genes associated with drought-, salt-, oxidative- and nutrient
      deficiency-stresses. We describe the examples from studies where abiotic stress
      related genes are characterized using VIGS. In addition, we describe the major
      advantages of VIGS over other currently available functional genomics tools. We
      also summarize the recent improvements, limitations and future prospects of using
      VIGS as a tool for studying plant responses to abiotic stresses. 

PMID- 25071808
TI  - Genome-based analysis of the transcriptome from mature chickpea root nodules.
AB  - Symbiotic nitrogen fixation (SNF) in root nodules of grain legumes such as
      chickpea is a highly complex process that drastically affects the gene expression
      patterns of both the prokaryotic as well as eukaryotic interacting cells. A
      successfully established symbiotic relationship requires mutual signaling
      mechanisms and a continuous adaptation of the metabolism of the involved cells to
      varying environmental conditions. Although some of these processes are well
      understood today many of the molecular mechanisms underlying SNF, especially in
      chickpea, remain unclear. Here, we reannotated our previously published
      transcriptome data generated by deepSuperSAGE (Serial Analysis of Gene
      Expression) to the recently published draft genome of chickpea to assess the root
      and nodule-specific transcriptomes of the eukaryotic host cells. The identified
      gene expression patterns comprise up to 71 significantly differentially expressed
      genes and the expression of twenty of these was validated by quantitative real
      time PCR with the tissues from five independent biological replicates. Many of
      the differentially expressed transcripts were found to encode proteins implicated
      in sugar metabolism, antioxidant defense as well as biotic and abiotic stress
      responses of the host cells, and some of them were already known to contribute to
      SNF in other legumes. The differentially expressed genes identified in this study
      represent candidates that can be used for further characterization of the complex
      molecular mechanisms underlying SNF in chickpea. 

PMID- 25071807
TI  - Regulation of Sucrose non-Fermenting Related Kinase 1 genes in Arabidopsis
      thaliana.
AB  - The Sucrose non-Fermenting Related Kinase 1 (SnRK1) proteins have been linked to
      regulation of energy and stress signaling in eukaryotes. In plants, there is a
      small SnRK1 gene family. While the SnRK1.1 gene has been well studied, the role
      other SnRK1 isoforms play in energy or stress signaling is less well understood.
      We used promoter:GUS analysis and found SnRK1.1 is broadly expressed, while
      SnRK1.2 is spatially restricted. SnRK1.2 is expressed most abundantly in
      hydathodes, at the base of leaf primordia, and in vascular tissues within both
      shoots and roots. We examined the impact that sugars have on SnRK1 gene
      expression and found that trehalose induces SnRK1.2 expression. Given that the
      SnRK1.1 and SnRK1.2 proteins are very similar at the amino acid level, we sought
      to address whether SnRK1.2 is capable of re-programming growth and development as
      has been seen previously with SnRK1.1 overexpression. While gain-of-function
      transgenic plants overexpressing two different isoforms of SnRK1.1 flower late as
      seen previously in other SnRK1.1 overexpressors, SnRK1.2 overexpressors flower
      early. In addition, SnRK1.2 overexpressors have increased leaf size and rosette
      diameter during early development, which is the opposite of SnRK1.1
      overexpressors. We also investigated whether SnRK1.2 was localized to similar
      subcellular compartments as SnRK1.1, and found that both accumulate in the
      nucleus and cytoplasm in transient expression assays. In addition, we found
      SnRK1.1 accumulates in small puncta that appear after a mechanical wounding
      stress. Together, these data suggest key differences in regulation of the SnRK1.1
      and SnRK1.2 genes in plants, and highlights differences overexpression of each
      gene has on the development of Arabidopsis. 

PMID- 25071809
TI  - A model for an early role of auxin in Arabidopsis gynoecium morphogenesis.
AB  - The female reproductive organ of angiosperms, the gynoecium, often consists of
      the fusion of multiple ovule-bearing carpels. It serves the important function of
      producing and protecting ovules as well as mediating pollination. The gynoecium
      has likely contributed to the tremendous success of angiosperms over their 160
      million year history. In addition, being a highly complex plant organ, the
      gynoecium is well suited to serving as a model system for use in the
      investigation of plant morphogenesis and development. The longstanding model of
      gynoecium morphogenesis in Arabidopsis holds that apically localized auxin
      biosynthesis in the gynoecium results in an apical to basal gradient of auxin
      that serves to specify along its length the development of style, ovary, and
      gynophore in a concentration-dependent manner. This model is based primarily on
      the observed effects of the auxin transport blocker N-1-naphthylphthalamic acid
      (NPA) as well as analyses of mutants of Auxin Response Factor (ARF) 3/ETTIN
      (ETT). Both NPA treatment and ett mutation disrupt gynoecium morphological
      patterns along the apical-basal axis. More than a decade after the model's
      initial proposal, however, the auxin gradient on which the model critically
      depends remains elusive. Furthermore, multiple observations are inconsistent with
      such an auxin-gradient model. Chiefly, the timing of gynoecium emergence and
      patterning occurs at a very early stage when the organ has little-to-no apical
      basal dimension. Based on these observations and current models of early leaf
      patterning, we propose an alternate model for gynoecial patterning. Under this
      model, the action of auxin is necessary for the early establishment of adaxial
      abaxial patterning of the carpel primordium. In this case, the observed gynoecial
      phenotypes caused by NPA and ett are due to the disruption of this early adaxial
      abaxial patterning of the carpel primordia. Here we present the case for this
      model based on recent literature and current models of leaf development. 

PMID- 25071810
TI  - Experimental data and computational modeling link auxin gradient and development
      in the Arabidopsis root.
AB  - The presence of an auxin gradient in the Arabidopsis root is crucial for proper
      root development and importantly, for stem cell niche (SCN) maintenance.
      Subsequently, developmental pathways in the root SCN regulate the formation of
      the auxin gradient. Combinations of experimental data and computational modeling
      enable the identification of pathways involved in establishing and maintaining
      the auxin gradient. We describe how the predictive power of these computational
      models is used to find how genes and their interactions tightly control the
      formation of an auxin maximum in the SCN. In addition, we highlight known
      connections between signaling pathways involving auxin and controlling patterning
      and development in Arabidopsis. 

PMID- 25071811
TI  - Ubiquitin-mediated control of seed size in plants.
AB  - Seed size in higher plants is an important agronomic trait, and is also crucial
      for evolutionary fitness. In flowering plants, the seed comprises three major
      anatomical components, the embryo, the endosperm and the seed coat, each with
      different genetic compositions. Therefore, seed size is coordinately determined
      by the growth of the embryo, endosperm and maternal tissue. Recent studies have
      revealed multiple pathways that influence seed size in plants. Several factors
      involved in ubiquitin-related activities have been recently known to determine
      seed size in Arabidopsis and rice. In this review, we summarize current knowledge
      of ubiquitin-mediated control of seed size and discuss the role of the ubiquitin
      pathway in seed size control. 

PMID- 25071812
TI  - Recent advancements to study flowering time in almond and other Prunus species.
AB  - Flowering time is an important agronomic trait in almond since it is decisive to
      avoid the late frosts that affect production in early flowering cultivars.
      Evaluation of this complex trait is a long process because of the prolonged
      juvenile period of trees and the influence of environmental conditions affecting
      gene expression year by year. Consequently, flowering time has to be studied for
      several years to have statistical significant results. This trait is the result
      of the interaction between chilling and heat requirements. Flowering time is a
      polygenic trait with high heritability, although a major gene Late blooming (Lb)
      was described in "Tardy Nonpareil." Molecular studies at DNA level confirmed this
      polygenic nature identifying several genome regions (Quantitative Trait Loci,
      QTL) involved. Studies about regulation of gene expression are scarcer although
      several transcription factors have been described as responsible for flowering
      time. From the metabolomic point of view, the integrated analysis of the
      mechanisms of accumulation of cyanogenic glucosides and flowering regulation
      through transcription factors open new possibilities in the analysis of this
      complex trait in almond and in other Prunus species (apricot, cherry, peach,
      plum). New opportunities are arising from the integration of recent advancements
      including phenotypic, genetic, genomic, transcriptomic, and metabolomics studies
      from the beginning of dormancy until flowering. 

PMID- 25071813
TI  - The role of branch architecture in assimilate production and partitioning: the
      example of apple (Malus domestica).
AB  - Understanding the role of branch architecture in carbon production and allocation
      is essential to gain more insight into the complex process of assimilate
      partitioning in fruit trees. This mini review reports on the current knowledge of
      the role of branch architecture in carbohydrate production and partitioning in
      apple. The first-order carrier branch of apple illustrates the complexity of
      branch structure emerging from bud activity events and encountered in many fruit
      trees. Branch architecture influences carbon production by determining leaf
      exposure to light and by affecting leaf internal characteristics related to leaf
      photosynthetic capacity. The dynamics of assimilate partitioning between branch
      organs depends on the stage of development of sources and sinks. The sink
      strength of various branch organs and their relative positioning on the branch
      also affect partitioning. Vascular connections between branch organs determine
      major pathways for branch assimilate transport. We propose directions for
      employing a modeling approach to further elucidate the role of branch
      architecture on assimilate partitioning. 

PMID- 25071814
TI  - Annotation and sequence diversity of transposable elements in common bean
      (Phaseolus vulgaris).
AB  - Common bean (Phaseolus vulgaris) is an important legume crop grown and consumed
      worldwide. With the availability of the common bean genome sequence, the next
      challenge is to annotate the genome and characterize functional DNA elements.
      Transposable elements (TEs) are the most abundant component of plant genomes and
      can dramatically affect genome evolution and genetic variation. Thus, it is
      pivotal to identify TEs in the common bean genome. In this study, we performed a
      genome-wide transposon annotation in common bean using a combination of homology
      and sequence structure-based methods. We developed a 2.12-Mb transposon database
      which includes 791 representative transposon sequences and is available upon
      request or from www.phytozome.org. Of note, nearly all transposons in the
      database are previously unrecognized TEs. More than 5,000 transposon-related
      expressed sequence tags (ESTs) were detected which indicates that some
      transposons may be transcriptionally active. Two Ty1-copia retrotransposon
      families were found to encode the envelope-like protein which has rarely been
      identified in plant genomes. Also, we identified an extra open reading frame
      (ORF) termed ORF2 from 15 Ty3-gypsy families that was located between the ORF
      encoding the retrotransposase and the 3'LTR. The ORF2 was in opposite
      transcriptional orientation to retrotransposase. Sequence homology searches and
      phylogenetic analysis suggested that the ORF2 may have an ancient origin, but its
      function is not clear. These transposon data provide a useful resource for
      understanding the genome organization and evolution and may be used to identify
      active TEs for developing transposon-tagging system in common bean and other
      related genomes. 

PMID- 25071816
TI  - Wheat and barley dehydrins under cold, drought, and salinity - what can LEA-II
      proteins tell us about plant stress response?
AB  - Dehydrins as a group of late embryogenesis abundant II proteins represent
      important dehydration-inducible proteins whose accumulation is induced by
      developmental processes (embryo maturation) as well as by several abiotic stress
      factors (low temperatures, drought, salinity). In the review, an overview of
      studies aimed at investigation of dehydrin accumulation patterns at transcript
      and protein levels as well as their possible functions in common wheat (Triticum
      aestivum), durum wheat (T. durum), and barley (Hordeum vulgare) plants exposed to
      various abiotic stress factors (cold, frost, drought, salinity) is provided.
      Possible roles of dehydrin proteins in an acquisition and maintenance of an
      enhanced frost tolerance are analyzed in the context of plant developmental
      processes (vernalization). Quantitative and qualitative differences as well as
      post-translational modifications in accumulated dehydrin proteins between barley
      cultivars revealing differential tolerance to drought and salinity are also
      discussed. Current knowledge on dehydrin role in wheat and barley response to
      major dehydrative stresses is summarized and the major challenges in dehydrin
      research are outlined. 

PMID- 25071815
TI  - Damage signals in the insect immune response.
AB  - Insects and mammals share an ancient innate immune system comprising both humoral
      and cellular responses. The insect immune system consists of the fat body, which
      secretes effector molecules into the hemolymph and several classes of hemocytes,
      which reside in the hemolymph and of protective border epithelia. Key features of
      wound- and immune responses are shared between insect and mammalian immune
      systems including the mode of activation by commonly shared microbial (non-self)
      patterns and the recognition of these patterns by dedicated receptors. It is
      unclear how metazoan parasites in insects, which lack these shared motifs, are
      recognized. Research in recent years has demonstrated that during entry into the
      insect host, many eukaryotic pathogens leave traces that alert potential hosts of
      the damage they have afflicted. In accordance with terminology used in the
      mammalian immune systems, these signals have been dubbed danger- or damage
      associated signals. Damage signals are necessary byproducts generated during
      entering hosts either by mechanical or proteolytic damage. Here, we briefly
      review the current stage of knowledge on how wound closure and wound healing
      during mechanical damage is regulated and how damage-related signals contribute
      to these processes. We also discuss how sensors of proteolytic activity induce
      insect innate immune responses. Strikingly damage-associated signals are also
      released from cells that have aberrant growth, including tumor cells. These
      signals may induce apoptosis in the damaged cells, the recruitment of immune
      cells to the aberrant tissue and even activate humoral responses. Thus, this
      ensures the removal of aberrant cells and compensatory proliferation to replace
      lost tissue. Several of these pathways may have been co-opted from wound healing
      and developmental processes. 

PMID- 25071818
TI  - Phosphorylation of unique domains of Src family kinases.
AB  - Members of the Src family of kinases (SFKs) are non-receptor tyrosine kinases
      involved in numerous signal transduction pathways. The catalytic, SH3 and SH2
      domains are attached to the membrane-anchoring SH4 domain through the
      intrinsically disordered "Unique" domains, which exhibit strong sequence
      divergence among SFK members. In the last decade, structural and biochemical
      studies have begun to uncover the crucial role of the Unique domain in the
      regulation of SFK activity. This mini-review discusses what is known about the
      phosphorylation events taking place on the SFK Unique domains, and their
      biological relevance. The modulation by phosphorylation of biologically relevant
      inter- and intra- molecular interactions of Src, as well as the existence of
      complex phosphorylation/dephosphorylation patterns observed for the Unique domain
      of Src, reinforces the important functional role of the Unique domain in the
      regulation mechanisms of the Src kinases and, in a wider context, of
      intrinsically disordered regions in cellular processes. 

PMID- 25071817
TI  - Glyco-engineering for biopharmaceutical production in moss bioreactors.
AB  - The production of recombinant biopharmaceuticals (pharmaceutical proteins) is a
      strongly growing area in the pharmaceutical industry. While most products to date
      are produced in mammalian cell cultures, namely Chinese hamster ovary cells,
      plant-based production systems gained increasing acceptance over the last years.
      Different plant systems have been established which are suitable for
      standardization and precise control of cultivation conditions, thus meeting the
      criteria for pharmaceutical production. The majority of biopharmaceuticals
      comprise glycoproteins. Therefore, differences in protein glycosylation between
      humans and plants have to be taken into account and plant-specific glycosylation
      has to be eliminated to avoid adverse effects on quality, safety, and efficacy of
      the products. The basal land plant Physcomitrella patens (moss) has been employed
      for the recombinant production of high-value therapeutic target proteins (e.g.,
      Vascular Endothelial Growth Factor, Complement Factor H, monoclonal antibodies,
      Erythropoietin). Being genetically excellently characterized and exceptionally
      amenable for precise gene targeting via homologous recombination, essential steps
      for the optimization of moss as a bioreactor for the production of recombinant
      proteins have been undertaken. Here, we discuss the glyco-engineering approaches
      to avoid non-human N- and O-glycosylation on target proteins produced in moss
      bioreactors. 

PMID- 25071819
TI  - An alternative hypothesis testing strategy for secondary phenotype data in case
      control genetic association studies.
AB  - Motivated by the challenges associated with accounting for the ascertainment when
      analyzing secondary phenotypes that are correlated with case-control status, Lin
      and Zeng have proposed a method that properly reflects the case-control sampling
      (Lin and Zeng, 2009). The Lin and Zeng method has the advantage of accurately
      estimating effect sizes for secondary phenotypes that are normally distributed or
      dichotomous. This method can be computationally intensive in practice under the
      null hypothesis when the likelihood surface that needs to be maximized can be
      relatively flat. We propose an extension of the Lin and Zeng method for
      hypothesis testing that uses proportional odds logistic regression to circumvent
      these computational issues. Through simulation studies, we compare the power and
      type-1 error rate of our method to standard approaches and Lin and Zeng's
      approach. 

PMID- 25071820
TI  - Using the zebrafish model for Alzheimer's disease research.
AB  - Rodent models have been extensively used to investigate the cause and mechanisms
      behind Alzheimer's disease. Despite many years of intensive research using these
      models we still lack a detailed understanding of the molecular events that lead
      to neurodegeneration. Although zebrafish lack the complexity of advanced
      cognitive behaviors evident in rodent models they have proven to be a very
      informative model for the study of human diseases. In this review we give an
      overview of how the zebrafish has been used to study Alzheimer's disease.
      Zebrafish possess genes orthologous to those mutated in familial Alzheimer's
      disease and research using zebrafish has revealed unique characteristics of these
      genes that have been difficult to observe in rodent models. The zebrafish is
      becoming an increasingly popular model for the investigation of Alzheimer's
      disease and will complement studies using other models to help complete our
      understanding of this disease. 

PMID- 25071821
TI  - Toward a systems-level understanding of gene regulatory, protein interaction, and
      metabolic networks in cyanobacteria.
AB  - Cyanobacteria are essential primary producers in marine ecosystems, playing an
      important role in both carbon and nitrogen cycles. In the last decade, various
      genome sequencing and metagenomic projects have generated large amounts of
      genetic data for cyanobacteria. This wealth of data provides researchers with a
      new basis for the study of molecular adaptation, ecology and evolution of
      cyanobacteria, as well as for developing biotechnological applications. It also
      facilitates the use of multiplex techniques, i.e., expression profiling by high
      throughput technologies such as microarrays, RNA-seq, and proteomics. However,
      exploration and analysis of these data is challenging, and often requires
      advanced computational methods. Also, they need to be integrated into our
      existing framework of knowledge to use them to draw reliable biological
      conclusions. Here, systems biology provides important tools. Especially, the
      construction and analysis of molecular networks has emerged as a powerful systems
      level framework, with which to integrate such data, and to better understand
      biological relevant processes in these organisms. In this review, we provide an
      overview of the advances and experimental approaches undertaken using multiplex
      data from genomic, transcriptomic, proteomic, and metabolomic studies in
      cyanobacteria. Furthermore, we summarize currently available web-based tools
      dedicated to cyanobacteria, i.e., CyanoBase, CyanoEXpress, ProPortal, Cyanorak,
      CyanoBIKE, and CINPER. Finally, we present a case study for the freshwater model
      cyanobacteria, Synechocystis sp. PCC6803, to show the power of meta-analysis, and
      the potential to extrapolate acquired knowledge to the ecologically important
      marine cyanobacteria genus, Prochlorococcus. 

PMID- 25071823
TI  - Roles of lncRNAs in pancreatic beta cell identity and diabetes susceptibility.
AB  - Type 2 diabetes usually ensues from the inability of pancreatic beta cells to
      compensate for incipient insulin resistance. The loss of beta cell mass,
      function, and potentially beta cell identity contribute to this dysfunction to
      extents which are debated. In recent years, long non-coding RNAs (lncRNAs) have
      emerged as potentially providing a novel level of gene regulation implicating
      critical cellular processes such as pluripotency and differentiation. With over
      1000 lncRNAs now identified in beta cells, there is growing evidence for their
      involvement in the above processes in these cells. While functional evidence on
      individual islet lncRNAs is still scarce, we discuss how lncRNAs could contribute
      to type 2 diabetes susceptibility, particularly at loci identified through genome
      wide association studies as affecting disease risk. 

PMID- 25071822
TI  - Identification of structural variation in mouse genomes.
AB  - Structural variation is variation in structure of DNA regions affecting DNA
      sequence length and/or orientation. It generally includes deletions, insertions,
      copy-number gains, inversions, and transposable elements. Traditionally, the
      identification of structural variation in genomes has been challenging. However,
      with the recent advances in high-throughput DNA sequencing and paired-end mapping
      (PEM) methods, the ability to identify structural variation and their respective
      association to human diseases has improved considerably. In this review, we
      describe our current knowledge of structural variation in the mouse, one of the
      prime model systems for studying human diseases and mammalian biology. We further
      present the evolutionary implications of structural variation on transposable
      elements. We conclude with future directions on the study of structural variation
      in mouse genomes that will increase our understanding of molecular architecture
      and functional consequences of structural variation. 

PMID- 25071824
TI  - Toward a systematic understanding of cancers: a survey of the pan-cancer study.
AB  - Studies on molecular aberrations of cancer patients have increased
      unprecedentedly in scale and accessibility, allowing large-scale integrative
      cross-cancer analysis. Pan-cancer study is becoming a valuable paradigm for
      cancer genomics. Here, we review recent advances in this field and highlight the
      potential challenges and directions especially from the computational angle. 

PMID- 25071825
TI  - The FMR1 gene, infertility, and reproductive decision-making: a review.
AB  - The strongest association between FMR1 and the ovary in humans is the increased
      risk of premature ovarian failure (POF) in women who carry the premutation level
      of CGG repeats (55-199 CGGs). Research on the FMR1 gene has extended to other
      endpoints of relevance in the OB/GYN setting for women, including infertility and
      ovarian hormones. After reviewing the nomenclature changes that have occurred in
      recent years, this article reviews the evidence linking the length of the FMR1
      repeat length to fertility and ovarian hormones (follicle stimulating hormone and
      anti-mullerian hormone as the primary methods to assess ovarian reserve in
      clinical settings). The literature is inconsistent on the association between the
      FMR1 trinucleotide repeat length and infertility. Elevated levels of follicle
      stimulating hormone have been found in women who carry the premutation; however
      the literature on the relationship between anti-mullerian hormone and the CGG
      repeat length are too disparate in design to make a summary statement. This
      article considers the implications of two transgenic mouse models (FXPM 130R and
      YAC90R) for theories on pathogenesis related to ovarian endpoints. Given the
      current screening/testing recommendations for reproductive age females and the
      variability of screening protocols in clinics, future research is recommended on
      pretest and posttest genetic counseling needs. Future research is also needed on
      ovarian health measurements across a range of CGG repeat lengths in order to
      interpret FMR1 test results in reproductive age women; the inconsistencies in the
      literature make it quite challenging to advise women on their risks related to
      FMR1 repeat length. 

PMID- 25071826
TI  - Computational methods for analysis and inference of kinase/inhibitor
      relationships.
AB  - The central role of kinases in virtually all signal transduction networks is the
      driving motivation for the development of compounds modulating their activity.
      ATP-mimetic inhibitors are essential tools for elucidating signaling pathways and
      are emerging as promising therapeutic agents. However, off-target ligand binding
      and complex and sometimes unexpected kinase/inhibitor relationships can occur for
      seemingly unrelated kinases, stressing that computational approaches are needed
      for learning the interaction determinants and for the inference of the effect of
      small compounds on a given kinase. Recently published high-throughput profiling
      studies assessed the effects of thousands of small compound inhibitors, covering
      a substantial portion of the kinome. This wealth of data paved the road for
      computational resources and methods that can offer a major contribution in
      understanding the reasons of the inhibition, helping in the rational design of
      more specific molecules, in the in silico prediction of inhibition for those
      neglected kinases for which no systematic analysis has been carried yet, in the
      selection of novel inhibitors with desired selectivity, and offering novel
      avenues of personalized therapies. 

PMID- 25071827
TI  - Grand challenges in evolutionary and population genetics: the importance of
      integrating epigenetics, genomics, modeling, and experimentation.

PMID- 25071828
TI  - Estimating directional epistasis.
AB  - Epistasis, i.e., the fact that gene effects depend on the genetic background, is
      a direct consequence of the complexity of genetic architectures. Despite this,
      most of the models used in evolutionary and quantitative genetics pay scant
      attention to genetic interactions. For instance, the traditional decomposition of
      genetic effects models epistasis as noise around the evolutionarily-relevant
      additive effects. Such an approach is only valid if it is assumed that there is
      no general pattern among interactions-a highly speculative scenario. Systematic
      interactions generate directional epistasis, which has major evolutionary
      consequences. In spite of its importance, directional epistasis is rarely
      measured or reported by quantitative geneticists, not only because its relevance
      is generally ignored, but also due to the lack of simple, operational, and
      accessible methods for its estimation. This paper describes conceptual and
      statistical tools that can be used to estimate directional epistasis from various
      kinds of data, including QTL mapping results, phenotype measurements in mutants,
      and artificial selection responses. As an illustration, I measured directional
      epistasis from a real-life example. I then discuss the interpretation of the
      estimates, showing how they can be used to draw meaningful biological inferences.

PMID- 25071829
TI  - On best practices in the development of bioinformatics software.

PMID- 25071831
TI  - A semi-automated motion-tracking analysis of locomotion speed in the C. elegans
      transgenics overexpressing beta-amyloid in neurons.
AB  - Multi-Worm Tracker (MWT) is a real-time computer vision system that can
      simultaneously quantify motional patterns of multiple worms. MWT provides several
      behavioral parameters, including analysis of accurate real-time locomotion speed
      in the nematode, Caenorhabditis elegans. Here, we determined locomotion speed of
      the Alzheimer's disease (AD) transgenic strain that over-expresses human beta
      amyloid1-42 (Abeta) in the neurons. The MWT analysis showed that the AD strain
      logged a slower average speed than the wild type (WT) worms. The results may be
      consistent with the observation that the AD patients with dementia tend to show
      deficits in physical activities, including frequent falls. The AD strain showed
      reduced ability of the eggs to hatch and slowed hatching of the eggs. Thus, over
      expression of Abeta in neurons causes negative effects on locomotion and
      hatchability. This study sheds light on new examples of detrimental effects that
      Abeta deposits can exhibit using C. elegans as a model system. The information
      gathered from this study indicates that the motion tracking analysis is a cost
      effective, efficient way to assess the deficits of Abeta over-expression in the
      C. elegans system. 

PMID- 25071832
TI  - Inferring ancestry from population genomic data and its applications.
AB  - Ancestry inference is a frequently encountered problem and has many applications
      such as forensic analyses, genetic association studies, and personal genomics.
      The main goal of ancestry inference is to identify an individual's population of
      origin based on our knowledge of natural populations. Because both self-reported
      ancestry in humans or the sampling location of an organism can be inaccurate for
      this purpose, the use of genetic markers can facilitate accurate and reliable
      inference of an individual's ancestral origins. At a higher level, there are two
      different paradigms in ancestry inference: global ancestry inference which tries
      to compute the genome-wide average of the population contributions and local
      ancestry inference which tries to identify the regional ancestry of a genomic
      segment. In this mini review, I describe the numerous approaches that are
      currently available for both kinds of ancestry inference from population genomic
      datasets. I first describe the general ideas underlying such inference methods
      and their relationship to one another. Then, I describe practical applications in
      which inference of ancestry has proven useful. Lastly, I discuss challenges and
      directions for future research work in this area. 

PMID- 25071833
TI  - Taking a chance on epigenetics.

PMID- 25071830
TI  - The Missing lnc(RNA) between the pancreatic beta-cell and diabetes.
AB  - Diabetes mellitus represents a group of complex metabolic diseases that result in
      impaired glucose homeostasis, which includes destruction of beta-cells or the
      failure of these insulin-secreting cells to compensate for increased metabolic
      demand. Despite a strong interest in characterizing the transcriptome of the
      different human islet cell types to understand the molecular basis of diabetes,
      very little attention has been paid to the role of long non-coding RNAs (lncRNAs)
      and their contribution to this disease. Here we summarize the growing evidence
      for the potential role of these lncRNAs in beta-cell function and dysregulation
      in diabetes, with a focus on imprinted genomic loci. 

PMID- 25071834
TI  - Evolutionary analysis of the cystatin family in three Schistosoma species.
AB  - The cystatin family comprises cysteine protease inhibitors distributed in 3
      subfamilies (I25A-C). Family members lacking cystatin activity are currently
      unclassified. Little is known about the evolution of Schistosoma cystatins, their
      physiological roles, and expression patterns in the parasite life cycle. The
      present study aimed to identify cystatin homologs in the predicted proteome of
      three Schistosoma species and other Platyhelminthes. We analyzed the amino acid
      sequence diversity focused in the identification of protein signatures and to
      establish evolutionary relationships among Schistosoma and experimentally
      validated human cystatins. Gene expression patterns were obtained from different
      developmental stages in Schistosoma mansoni using microarray data. In
      Schistosoma, only I25A and I25B proteins were identified, reflecting little
      functional diversification. I25C and unclassified subfamily members were not
      identified in platyhelminth species here analyzed. The resulting phylogeny placed
      cystatins in different clades, reflecting their molecular diversity. Our findings
      suggest that Schistosoma cystatins are very divergent from their human homologs,
      especially regarding the I25B subfamily. Schistosoma cystatins also differ
      significantly from other platyhelminth homologs. Finally, transcriptome data
      publicly available indicated that I25A and I25B genes are constitutively
      expressed thus could be essential for schistosome life cycle progression. In
      summary, this study provides insights into the evolution, classification, and
      functional diversification of cystatins in Schistosoma and other Platyhelminthes,
      improving our understanding of parasite biology and opening new frontiers in the
      identification of novel therapeutic targets against helminthiases. 

PMID- 25071835
TI  - Genetic anchoring of whole-genome shotgun assemblies.
AB  - The recent advances in sequencing throughput and genome assembly algorithms have
      established whole-genome shotgun (WGS) assemblies as the cornerstone of the
      genomic infrastructure for many species. WGS assemblies can be constructed with
      comparative ease and give a comprehensive representation of the gene space even
      of large and complex genomes. One major obstacle in utilizing WGS assemblies for
      important research applications such as gene isolation or comparative genomics
      has been the lack of chromosomal positioning and contextualization of short
      sequence contigs. Assigning chromosomal locations to sequence contigs required
      the construction and integration of genome-wide physical maps and dense genetic
      linkage maps as well as synteny to model species. Recently, methods to rapidly
      construct ultra-dense linkage maps encompassing millions of genetic markers from
      WGS sequencing data of segregating populations have made possible the direct
      assignment of genetic positions to short sequence contigs. Here, we review recent
      developments in the integration of WGS assemblies and sequence-based linkage
      maps, discuss challenges for further improvement of the methodology and outline
      possible applications building on genetically anchored WGS assemblies. 

PMID- 25071836
TI  - Functional implications of long non-coding RNAs in the pancreatic islets of
      Langerhans.
AB  - Type-2 diabetes (T2D) is a complex disease characterized by insulin resistance in
      target tissues and impaired insulin release from pancreatic beta cells. As
      central tissue of glucose homeostasis, the pancreatic islet continues to be an
      important focus of research to understand the pathophysiology of the disease. The
      increased access to human pancreatic islets has resulted in improved knowledge of
      islet function, and together with advances in RNA sequencing and related
      technologies, revealed the transcriptional and epigenetic landscape of human
      islet cells. The discovery of thousands of long non-coding RNA (lncRNA)
      transcripts highly enriched in the pancreatic islet and/or specifically expressed
      in the beta-cells, points to yet another layer of gene regulation of many
      hitherto unknown mechanistic principles governing islet cell functions. Here we
      review fundamental islet physiology and propose functional implications of the
      lncRNAs in islet development and endocrine cell functions. We also take into
      account important differences between rodent and human islets in terms of
      morphology and function, and suggest how species-specific lncRNAs may partly
      influence gene regulation to define the unique phenotypic identity of an organism
      and the functions of its constituent cells. The implication of primate-specific
      lncRNAs will be far-reaching in all aspects of diabetes research, but most
      importantly in the identification and development of novel targets to improve
      pancreatic islet cell functions as a therapeutic approach to treat T2D. 

PMID- 25071837
TI  - Objective: biochemical function.

PMID- 25071839
TI  - Systems genetics of obesity in an F2 pig model by genome-wide association,
      genetic network, and pathway analyses.
AB  - Obesity is a complex condition with world-wide exponentially rising prevalence
      rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare
      consequences have led to a raised interest in a better understanding of the
      biological and genetic background. To date, whole genome investigations focusing
      on single genetic variants have achieved limited success, and the importance of
      including genetic interactions is becoming evident. Here, the aim was to perform
      an integrative genomic analysis in an F2 pig resource population that was
      constructed with an aim to maximize genetic variation of obesity-related
      phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association
      (GWA) analysis was performed on the Obesity Index to locate candidate genomic
      regions that were further validated using combined Linkage Disequilibrium Linkage
      Analysis and investigated by evaluation of haplotype blocks. We built Weighted
      Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic
      correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA
      results and SNP modules detected by WISH and DW analyses were further
      investigated by functional enrichment analyses. The functional annotation of SNPs
      revealed several genes associated with obesity, e.g., NPC2 and OR4D10. Moreover,
      gene enrichment analyses identified several significantly associated pathways,
      over and above the GWA study results, that may influence obesity and obesity
      related diseases, e.g., metabolic processes. WISH networks based on genotypic
      correlations allowed further identification of various gene ontology terms and
      pathways related to obesity and related traits, which were not identified by the
      GWA study. In conclusion, this is the first study to develop a (genetic) obesity
      index and employ systems genetics in a porcine model to provide important
      insights into the complex genetic architecture associated with obesity and many
      biological pathways that underlie it. 

PMID- 25071838
TI  - Handling tRNA introns, archaeal way and eukaryotic way.
AB  - Introns are found in various tRNA genes in all the three kingdoms of life.
      Especially, archaeal and eukaryotic genomes are good sources of tRNA introns that
      are removed by proteinaceous splicing machinery. Most intron-containing tRNA
      genes both in archaea and eukaryotes possess an intron at a so-called canonical
      position, one nucleotide 3' to their anticodon, while recent bioinformatics have
      revealed unusual types of tRNA introns and their derivatives especially in
      archaeal genomes. Gain and loss of tRNA introns during various stages of
      evolution are obvious both in archaea and eukaryotes from analyses of comparative
      genomics. The splicing of tRNA molecules has been studied extensively from
      biochemical and cell biological points of view, and such analyses of eukaryotic
      systems provided interesting findings in the past years. Here, I summarize recent
      progresses in the analyses of tRNA introns and the splicing process, and try to
      clarify new and old questions to be solved in the next stages. 

PMID- 25071841
TI  - Emerging functional similarities and divergences between Drosophila Spargel/dPGC
      1 and mammalian PGC-1 protein.
AB  - Peroxisome Proliferator Activated Receptor Gamma Co-activator-1 (PGC-1) is a well
      conserved protein among all chordates. Entire Drosophila species subgroup carries
      a PGC-1 homolog in their genome called spargel/dPGC-1 showing very little
      divergence. Recent studies have reported that significant functional similarities
      are shared between vertebrate and invertebrate PGC-1's based on their role in
      mitochondrial functions and biogenesis, gluconeogenesis, and most likely in
      transcription and RNA processing. With the help of genetic epistasis analysis, we
      established that Drosophila Spargel/dPGC-1 affects cell growth process as a
      terminal effector in the Insulin-TOR signaling pathway. The association between
      Spargel/dPGC-1 and Insulin signaling could also explain its role in the aging
      process. Here we provided a further comparison between Spargel/dPGC-1 and PGC-1
      focusing on nuclear localization, oxidative stress resistance, and a possible
      role of Spargel/dPGC-1 in oogenesis reminiscing the role of Spargel in
      reproductive aging like many Insulin signaling partners. This led us to
      hypothesize that the discovery of newer biological functions in Drosophila
      Spargel/dPGC-1 will pave the way to uncover novel functional equivalents in
      mammals. 

PMID- 25071840
TI  - Using a medium-throughput comet assay to evaluate the global DNA methylation
      status of single cells.
AB  - The comet assay is a simple and cost effective technique, commonly used to
      analyze and quantify DNA damage in individual cells. The versatility of the comet
      assay allows introduction of various modifications to the basic technique. The
      difference in the methylation sensitivity of the isoschizomeric restriction
      enzymes HpaII and MspI are used to demonstrate the ability of the comet assay to
      measure the global DNA methylation level of individual cells when using cell
      cultures. In the experiments described here, a medium-throughput comet assay and
      methylation sensitive comet assay are combined to produce a methylation sensitive
      medium-throughput comet assay to measure changes in the global DNA methylation
      pattern in individual cells under various growth conditions. 

PMID- 25071842
TI  - Role of microRNA-146a in normal and malignant hematopoietic stem cell function.
AB  - Regulation of hematopoiesis is controlled by microRNAs (miRNAs). In this review,
      we focus on miR-146a, and its role in regulating normal and malignant
      hematopoiesis. miR-146a is a negative regulator of immune cell activation by
      repressing two targets, TRAF6 and IRAK1. Genetic deletion of miR-146a confirmed a
      role of miR-146a during innate immune signaling as well as for hematopoietic stem
      cell function. miR-146a is also implicated in the pathogenesis of human
      myelodysplastic syndromes (MDSs) as it is located within a commonly deleted
      region on chromosome 5, and miR-146a-deficient mice exhibit features of an MDS
      like disease. With new insight into miR-146a through genetic and expression
      analyses, we highlight and discuss the recent advances in the understanding of
      miR-146a in physiological hematopoiesis during steady-state and inflammation, as
      well as in MDS. 

PMID- 25071843
TI  - The potential of epigenetic therapies in neurodegenerative diseases.
AB  - Available treatments for neurodegenerative diseases such as Alzheimer's disease,
      Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, do
      not arrest disease progression but mainly help keeping patients from getting
      worse for a limited period of time. Increasing evidence suggests that epigenetic
      mechanisms such as DNA methylation and histone tail modifications are dynamically
      regulated in neurons and play a fundamental role in learning and memory
      processes. In addition, both global and gene-specific epigenetic changes and
      deregulated expression of the writer and eraser proteins of epigenetic marks are
      believed to contribute to the onset and progression of neurodegeneration. Studies
      in animal models of neurodegenerative diseases have highlighted the potential
      role of epigenetic drugs, including inhibitors of histone deacetylases and methyl
      donor compounds, in ameliorating the cognitive symptoms and preventing or
      delaying the motor symptoms of the disease, thereby opening the way for a
      potential application in human pathology. 

PMID- 25071844
TI  - Preservation of ovarian function during chemotherapy and radiotherapy in young
      women with malignancies.
AB  - Malignancies are not rare in girl and women during their reproductive years. Over
      the past three decades, the survival rate for cancer has been improving due to
      progress in cancer diagnosis and treatment. These patients frequently experience
      a variety of treatment, and disease-related side effects that diminish their
      quality of life during and after treatment; among these are loss of fertility and
      sexual dysfunction. There have been recent advances in the field of fertility
      preservation, which can allow many of these genital cancer survivors to have
      children in the future. This topic review discusses available options and
      specific strategies for fertility preservation in adolescent and young women with
      malignancies who wish to preserve their ability to become pregnant in the future.

PMID- 25071845
TI  - Prevalence and patterns of Y chromosome microdeletion in infertile men with
      azoospermia and oligzoospermia in Northeast China.
AB  - BACKGROUND: In some cases infertile men showed small deletions of specific genes
      in the Y chromosome. It had been confirmed, these deleted genes are greatly
      associated with spermatogenic failure. However, the frequency and the patterns of
      such microdeletions among infertile men are not clearly clarified. OBJECTIVE: We
      sought to determine the frequency and the patterns of Y chromosome microdeletions
      in azoospermic and oligozoospermic infertile men in Northeast China, and try to
      optimize the selection of sequence tagged sites (STSs) of AZF microdeletions in
      multiplex polymerase chain reaction (PCR). MATERIALS AND METHODS: 720 azoospermic
      and 330 oligozoospermic infertile men, from Northeast China were included in this
      retrospective study during May 2008 to November 2012. Semen analysis was
      performed according to the World Health Organization guidelines. Y chromosome
      microdeletions were detected by polymerase chain reaction assays. G-banding
      method was used for chromosome Karyotype analysis. Chi-square tests were used to
      compare patterns of Y chromosome microdeletions in azoospermic and
      oligozoospermic patients. RESULTS: Of 1050 infertile men, 12.95% cases had shown
      Y chromosome microdeletions, and 19.43% of cases showed abnormal chromosomal
      karyotype. Deletions in AZFc region was the most frequent 75.00%, followed by
      deletions in AZFb region 13.33%, AZFbc region 09.62%, and AZFa region 2.22%. All
      oligozoospermic patients showed presence of sY84, sY86, sY127, and sY134.
      Deletion of sY127 (p=0.0101) and sY157 (p=0.0043) showed significant difference
      between azoospermic group and oligozoospermic group. CONCLUSION: Deletions of
      sY127 may relate to azoospermia while sY84, sY86, sY127 can be ignored in AZF
      screening for oligozoospermic patients.

PMID- 25071846
TI  - Expression of Toll-like receptors 7-10 in human fallopian tubes.
AB  - BACKGROUND: The human female reproductive tract (FRT) is constantly deal with the
      invading pathogens. Recognition of these pathogens is attributed to the family of
      Toll like receptors (TLR) as a major part of the innate immune system. We and
      others have previously revealed that TLRs1-6 express in the female reproductive
      tract. However, more studies should be done to detect TLRs 7-10 in the female
      reproductive tract, especially in the fallopian tubes. OBJECTIVE: To examine the
      expression of TLRs7-10 in human fallopian tube tissue. MATERIALS AND METHODS:
      Using immunostaining techniques, distribution of TLR7-10 was studied in surgical
      sections from the uterine tubes, obtained from patients undergoing tubal ligation
      and hysterectomy for benign gynecological conditions. RT-PCR was used to show the
      existence of TLR7-10 genes in fallopian tube tissue. RESULTS: TLR7-10 proteins
      were detected in the fallopian tube epithelium, although the intensity of
      staining was not equal in cases. TLR7-10 genes were expressed in human fallopian
      tube tissue. CONCLUSION: This study indicates that TLR7-10 is expressed in
      fallopian tubes tissues, and may play an important role in microbial recognition,
      and in host defense against ascending infection.

PMID- 25071847
TI  - Investigation on estrogen receptor alpha gene polymorphisms in Iranian women with
      recurrent pregnancy loss.
AB  - BACKGROUND: Recurrent pregnancy loss (RPL) is a multifactorial disorder.
      Environmental factors and genetics can affect pregnancy outcomes. OBJECTIVE:
      Conflicting data suggest an association between estrogen receptor alpha (ESR1)
      gene polymorphisms and RPL. In this study, such association was investigated in
      Iranian women with RPL. MATERIALS AND METHODS: In this case control study, blood
      samples were collected from 244 women with a history of three or more consecutive
      pregnancy losses and 104 healthy women with at least two live births. Using
      polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP),
      we studied -397C/T and -351A/G polymorphisms on ESR1 gene in case and control
      subjects. RESULTS: The genotypic frequencies of -397C/T and -351A/G polymorphisms
      on ESR1were not significantly different between RPL and control groups (p=0.20
      and p=0.09, respectively). A significantly negative correlation was observed
      between -397C/T and -351A/G (r=-0.852, p<0.001) in RPL women and complete linkage
      disequilibrium between the investigated polymorphisms was found (D': 0.959; r
      square= 0.758, p<0.001). CONCLUSION: This investigation suggests that the
      analyzed polymorphisms on ESR1gene are not associated with an increased risk of
      RPL in the studied population.

PMID- 25071848
TI  - Protective effect of Urtica dioica L against nicotine-induced damage on sperm
      parameters, testosterone and testis tissue in mice.
AB  - BACKGROUND: Nicotine consumption can decrease fertility drive in males by
      inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a
      multipurpose herb in traditional medicine for which some anti-oxidative and anti
      inflammatory properties have been identified. OBJECTIVE: The main goal is to
      investigate whether the U.dioica could inhibit nicotine adverse effects on sperm
      cells viability, count, motility, and testis histology and testosterone hormone.
      MATERIALS AND METHODS: In this study, hydro-alcoholic extract of U.dioica was
      prepared and various doses of U.dioica (0, 10, 20, and 50 mg/kg) and U.dioica
      plus nicotine (0, 10, 20, and 50 mg/kg) were administered intraperitoneally to 56
      male mice for 28 consequent days. These mice were randomly assigned to 8 groups
      (n=7) and sperm parameters (sperm cells viability, count, motility, and
      morphology), testis and prostate weight, testis histology and testosterone
      hormone were analyzed and compared. RESULTS: The results indicated that nicotine
      administration (0.5 mg/kg) significantly decreased testosterone level, count and
      motility of sperm cells, and testis weight compared to control group (p=0.00).
      However, increasing the dose of U.dioica significantly boosted motility, count,
      normal morphology of sperm cells, seminiferous tubules diameter, and testosterone
      in all groups compared to control (p=0.00) and testis weight in 20 and 50 mg/kg
      doses in comparison with control group (p=0.00). CONCLUSION: It seems that
      U.dioica hydro-alcoholic extract administration could increase the quality of
      spermatozoa and inhibits nicotine-induced adverse effects on sperm parameters.

PMID- 25071849
TI  - Comparison of clinical outcomes between fresh embryo transfers and frozen-thawed
      embryo transfers.
AB  - BACKGROUND: Advances in embryo culture technology and cryopreservation have led
      to a shift in in vitro fertilization (IVF) from early fresh or frozen-thawed
      cleavage embryo transfer to fresh or frozen-thawed blastocyst stage transfer.
      OBJECTIVE: To compare the clinical outcomes of fresh embryo transfers and frozen
      thawed embryo transfers. MATERIALS AND METHODS: In this retrospective case
      control study, patients undergoing IVF cycles from January 2012 to December 2012
      were enrolled in Assisted Reproduction of Wuhan Union Hospital were enrolled. A
      total of 1891 cycle contains 1150 fresh embryo transfers and 741 frozen-thawed
      embryo transfers were studied. All data were transferred directly to SPSS 18 and
      analyzed. RESULTS: Clinical pregnancy rates of fresh cleavage-stage embryo
      transfers compared with fresh blastocyst transfers, frozen-thawed cleavage-stage
      embryo transfers, post thaw cleavage-stage extended blastocyst culture transfers
      and frozen-thawed blastocyst transfers were 52.7%, 35.88%, 35.29%, 47.75%, 59.8%
      in patients under 35 years of ages and 41.24%, 26.92%, 11.32%, 46.15%, 55.8% in
      patients older than 35 years old, respectively. The multiple pregnancy rates,
      abortion rates and ectopic pregnancy rates did not differ significantly among the
      five groups. CONCLUSION: The clinical pregnancy rates were not different
      significantly between fresh cleavage-stage embryo transfers and fresh blastocyst
      transfers. But the clinical pregnancy rate of frozen-thawed blastocyst transfer
      was the highest among fresh/frozen-thawed embryo transfers.

PMID- 25071850
TI  - Vagifem is superior to vaginal Premarin in induction of endometrial thickness in
      the frozen-thawed cycle patients with refractory endometria: A randomized
      clinical trial.
AB  - BACKGROUND: Embryo transfer to a developed endometrium is an important prognostic
      factor in frozen-thawed embryo transfer cycle outcome. Vaginal estrogen, such as
      Vagifem vaginal tablets and Premarin vaginal cream, is a regimen used for the
      patients with refractive endometria. OBJECTIVE: Our objective was to compare the
      effects of Vagifem and Premarin on the endometrial thickness of the patients with
      refractive endometria. MATERIALS AND METHODS: In this randomized clinical trial,
      30 patients with refractive endometria in frozen-thawed embryo transfer cycles
      received Vagifem vaginal tablets and 30 women received Premarin vaginal cream.
      Endometrial thickness was measured on the 14th day of drug administration.
      RESULTS: Comparing the endometrial thicknesses of the two groups showed that the
      endometria of the Vagifem group was significantly thicker than that of the
      Premarin group (5.93+/-0.38 vs. 6.74+/-0.32; p<0.001). CONCLUSION: Vagifem is
      superior to Premarin in induction of endometrial thickness in frozen-thawed
      embryo transfer cycles in the patients with refractive endometria.

PMID- 25071851
TI  - Ultrasound detection of placenta accreta in the first trimester of pregnancy.
AB  - BACKGROUND: Placenta accreta is considered a life-threatening condition and the
      main cause of maternal mortality. Prenatal diagnosis of placenta accreta usually
      is made by clinical presentation, imaging studies like ultrasound and MRI in the
      second and third trimester. OBJECTIVE: To determine accuracy of ultrasound
      findings for placenta accreta in the first trimester of pregnancy. MATERIALS AND
      METHODS: In a longitudinal study 323 high risk patients for placenta accreta were
      assessed. The eligible women were examined by vaginal and abdominal ultrasound
      for gestational sac and placental localization and they were followed up until
      the end of pregnancy. The ultrasound findings were compared with
      histopathological examinations as a gold standard. The sensitivity, specificity,
      positive and negative predictive value of ultrasound were estimated for the first
      trimester and compared with other 2 trimesters in the case of repeated ultrasound
      examination. RESULTS: Ultrasound examinations in the first trimester revealed
      that 28 cases had the findings in favor of placenta accreta which ultimately was
      confirmed in 7 cases. The ultrasound sensitivity and specificity for detecting
      placenta accreta in the first trimester was 41% [95% CI: 16.2-62.7] and 88% [95%
      CI: 88.2-94.6] respectively. CONCLUSION: Ultrasound screening for placenta
      accreta in the first trimester of pregnancy could not achieve the high
      sensitivity as second and third trimester of pregnancy.

PMID- 25071852
TI  - Elevated serum progesterone/ MII oocyte ratio on the day of human chorionic
      gonadotropin administration can predict impaired endometrial receptivity.
AB  - BACKGROUND: Increased serum progesterone on the day of human chorionic
      gonadotropin administration may affect in vitro fertilization (IVF) outcome.
      OBJECTIVE: The aim of this study was to evaluate whether progesterone elevation
      on the day of human chorionic gonadotropin administration is associated with poor
      IVF outcome. MATERIALS AND METHODS: To determine the relationship between serum
      progesterone on the day of HCG and the outcome of IVF-embryo transfer treatment,
      378 infertile patients undergoing IVF-embryo transfer at Yazd Research and
      Clinical Center for Infertility from October 2009 to March 2011 were
      prospectively studied. RESULTS: In this study, absolute p-value and P/E2 ratio
      were not a good predictor outcome of in-vitro fertilization but progesterone per
      metaphase II were predictive of implantation rate and pregnancy rate with
      statistically significant results but had no effect on the fertilization rate.
      CONCLUSION: We suggest avoided the increased progesterone that the cause of
      advanced endometrial maturation and impaired endometrial receptivity. If the
      progesterone is greater than 0.32 per oocyte metaphase II, the embryo transfer
      can be canceled and freezing all embryos for future transfer must be considered,
      to increase acceptance of the endometrium and thus increase the success rate.

PMID- 25071853
TI  - A comparative cohort study for detecting the incidence of trisomy 21 in ART and
      non-ART neonates.
AB  - BACKGROUND: One of the most important points concerning the patients who undergo
      assisted reproductive techniques (ART) for getting pregnant can be the possible
      neonatal chromosomal abnormalities as a result of these methods. OBJECTIVE: This
      study was conducted to help answering a part of this question. MATERIALS AND
      METHODS: This is a historical cohort study from April 2006 to April 2007. Data
      were collected from women admitted in Mehregan Hospital and Esfahan Infertility
      Center. 225 of 2000 infertile women who had taken ART methods and 225 of 1800
      women undergoing no ART treatment were included in our study. All of the cases
      were aged 35 or more. Data were obtained from patient files from 2 infertility
      centers of Isfahan, Iran. RESULTS: Chromosomal analysis was successfully
      performed for all clinically suspicious infants for trisobmy 21. As a result, 4
      cases of trisomy 21 in ART group and 7 in non-ART group were found. Two cases
      from IUI, 1 case of IVF and 1 of ICSI were found to have trisomy 21 in infants.
      There was no statistically difference in occurring trisomy 21 in our two groups
      of study and this was also the same for women undergoing IVF and ICSI.
      CONCLUSION: ART methods did not increase the rate of Trisomy 21 according to our
      study although we found less in ART group, it was not statistically significant.

PMID- 25071854
TI  - Coexisting pelvic tuberculosis and endometriosis presenting in an infertile
      woman: Report of a rare case.
AB  - BACKGROUND: Primary and secondary infertility are the most common presenting
      symptom in patients with pelvic tuberculosis (PT). Endometriosis is commonly
      associated with an increased risk of infertility. CASE: Here, we report a rare
      case of coexisting PT and endometriosis in a 30-year- old woman, and the effects
      of controlled ovarian stimulation on reactivation of pathogen. CONCLUSION:
      Coexisting endometriosis and tuberculosis of fallopian tube and ovary, as in
      present case, may alter clinical and radiological features, leading to difficulty
      in diagnosis. Early diagnosis with surgical exploration and adequate treatment
      can improve the chances of conception and also minimize morbidity.

PMID- 25071856
TI  - Auto-injector needle length may be inadequate to deliver epinephrine
      intramuscularly in women with confirmed food allergy.
AB  - BACKGROUND: Epinephrine auto-injectors are the standard first aid treatment for
      anaphylaxis. Intramuscular delivery into the anterolateral aspect of the thigh is
      recommended for optimal onset of action of epinephrine. The most frequently
      prescribed auto-injector in North America and Canada is the EpiPen((r)), which
      has a needle length of 15.2 mm. Currently, it is unknown whether this needle
      length is adequate for intramuscular delivery of epinephrine in adult patients at
      risk of anaphylaxis. METHODS: One hundred consecutive adult patients with
      confirmed food allergy requiring an epinephrine auto-injector were recruited.
      Skin to muscle depth (STMD) at the right mid-anterolateral thigh was measured
      using ultrasound under minimal (min) and maximum (max) pressure. The EpiPen((r))
      needle length was considered adequate if STMDmax was <=15.2 mm. Baseline
      characteristics including age, gender, ethnicity, and body mass index (BMI) were
      compared in patients with STMDmax <=15.2 mm vs. >15.2 mm. RESULTS: The
      EpiPen((r)) needle length of 15.2 mm was inadequate for intramuscular delivery in
      19 of the 100 enrolled patients (19%), all of whom were female; 28% of women had
      a STMDmax >15.2 mm. The mean STMDmax in the <=15.2-mm and >15.2-mm groups were 9
      +/- 4 mm and 20 +/- 4 mm, respectively (p = 0.0001). Linear regression analysis
      found BMI to be significantly associated with STMDmax after adjusting for age (p
      < 0.001). CONCLUSIONS: The needle length of the epinephrine auto-injectors may
      not be adequate for intramuscular delivery of epinephrine in a large proportion
      of women with food allergy; this may impact morbidity and mortality from
      anaphylaxis in this patient population.

PMID- 25071855
TI  - The potential mechanistic link between allergy and obesity development and infant
      formula feeding.
AB  - This article provides a new view of the cellular mechanisms that have been
      proposed to explain the links between infant formula feeding and the development
      of atopy and obesity. Epidemiological evidence points to an allergy- and obesity
      preventive effect of breastfeeding. Both allergy and obesity development have
      been traced back to accelerated growth early in life. The nutrient-sensitive
      kinase mTORC1 is the master regulator of cell growth, which is predominantly
      activated by amino acids. In contrast to breastfeeding, artificial infant formula
      feeding bears the risk of uncontrolled excessive protein intake overactivating
      the infant's mTORC1 signalling pathways. Overactivated mTORC1 enhances S6K1
      mediated adipocyte differentiation, but negatively regulates growth and
      differentiation of FoxP3(+) regulatory T-cells (Tregs), which are deficient in
      atopic individuals. Thus, the "early protein hypothesis" not only explains
      increased mTORC1-mediated infant growth but also the development of mTORC1-driven
      diseases such as allergy and obesity due to a postnatal deviation from the
      appropriate axis of mTORC1-driven metabolic and immunologic programming.
      Remarkably, intake of fresh unpasteurized cow's milk exhibits an allergy
      preventive effect in farm children associated with increased FoxP3(+) Treg
      numbers. In contrast to unprocessed cow's milk, formula lacks bioactive immune
      regulatory microRNAs, such as microRNA-155, which plays a major role in FoxP3
      expression. Uncontrolled excessive protein supply by formula feeding associated
      with the absence of bioactive microRNAs and bifidobacteria in formula apparently
      in a synergistic way result in insufficient Treg maturation. Treg deficiency
      allows Th2-cell differentiation promoting the development of allergic diseases.
      Formula-induced mTORC1 overactivation is thus the critical mechanism that
      explains accelerated postnatal growth, allergy and obesity development on one
      aberrant pathway. 

PMID- 25071857
TI  - Impact of immediate evaluation of touch imprint cytology from computed tomography
      guided core needle biopsies of mass lesions: Single institution experience.
AB  - BACKGROUND: Computed tomography (CT) guided core needle biopsy (CT-guided CNB) is
      a minimally invasive, safe and effective manner of tissue sampling in many
      organs. The aim of our study is to determine the impact of on-site evaluation of
      touch imprint cytology (TIC) to minimize the number of passes required to obtain
      adequate tissue for diagnosis. DESIGN: A retrospective review of all CT-guided
      CNBs performed during 4 year period, where pathologists were present for on-site
      TIC evaluation. Each case was evaluated for the number of passes required before
      TIC was interpreted as adequate for diagnosis. RESULTS: A total of 140 CT-guided
      CNBs were included in the study (liver, lung, kidney, sacral, paraspinal,
      omental, splenic and adrenal masses). Of the 140 cases, 109 were diagnosed as
      malignant, 28 as benign and three insufficient. In 106 cases (75.7%), the
      biopsies were determined adequate by TIC on the first pass, 19 cases (13%) on the
      second pass and 7 cases (5%) on the third pass. Only in 5 cases (3.6%), more than
      three passes were required before diagnostic material was obtained. Three cases
      (2.14%) were interpreted as inadequate both on TIC and on the final diagnosis. Of
      the biopsies deemed adequate on the first pass, 71% resulted in either
      termination of the procedure, or only one additional pass was obtained. In five
      cases, based on the TIC evaluation, a portion of the sample was sent for either
      flow cytometric analysis or cytogenetic studies. CONCLUSIONS: In the majority of
      cases, adequate material was obtained in the first pass of CT-guided CNB and once
      this was obtained, either no additional passes, or one additional pass was
      performed. This study demonstrates the utility of on-site evaluation in
      minimizing the number of passes required for obtaining adequate diagnostic
      material and for proper specimen triage for ancillary studies, which in turn
      decreases the risk to the patient and costs. However, tumor exhaustion in the
      tissue as a result of TIC is an important pitfall of the procedure, which
      occurred in 9 (8.2%) of our malignant cases.

PMID- 25071858
TI  - Microcystic variant malignant mesothelioma presenting as a localized paraspinal
      mass.
AB  - A 58-year-old man presented with productive cough and fever. Computed tomography
      (CT) scan of the chest showed an upper right paraspinal mass. CT-guided fine
      needle aspiration biopsy showed lobules of vacuolated cells against a background
      of myxoid material. The cells demonstrated moderate to severe nuclear atypia and
      occasional mitoses. Immunohistochemistry revealed tumor cells to be
      immunoreactive for calretinin, WT-1, D2-40, cytokeratin (CK) 7, AE1/AE3, high
      molecular weight keratin, vimentin and epithelial membrane antigen, and negative
      for thyroid transcription factor-1, Ber-EP4, carcinoembryonic antigen, S100
      protein, CK20, and CDX2. The combined morphologic and immunohistochemical
      findings confirmed the diagnosis of microcystic variant of localized malignant
      mesothelioma. The subsequent lung resection showed a pleural-based mass in the
      right upper lobe and confirmed the diagnosis. Awareness of the existence of
      unusual morphologic variants and localized forms of mesothelioma are necessary to
      avoid misdiagnosis of fine needle biopsy samples. Recognition of characteristic
      cytomorphologic features along with optimal use of panel of immunohistochemistry
      studies is crucial for making a specific diagnosis. 

PMID- 25071859
TI  - Crystal storing histiocytosis associated with marginal zone B-cell lymphoma: A
      rare initial clinical presentation diagnosed by fine-needle aspiration.

PMID- 25071860
TI  - Pancreaticobiliary tract cytology: Journey toward "Bethesda" style guidelines
      from the Papanicolaou Society of Cytopathology.

PMID- 25071861
TI  - Evaluation of the safety and immunogenicity in United Kingdom laboratory workers
      of a combined Haemophilus influenzae type b and meningococcal capsular group C
      conjugate vaccine.
AB  - BACKGROUND: Although a combined Haemophilus influenzae type b (Hib)/meningococcal
      capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein
      (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack
      of data on safety and efficacy, certain patient groups at high risk of MenC
      and/or Hib disease are recommended to receive it. Laboratory workers working with
      Hib and/or MenC cultures may be at a potentially increased risk of acquiring
      infectious diseases and vaccination is therefore an important safety
      consideration. We undertook a clinical trial to investigate the safety and
      immunogenicity of Hib/MenC-TT vaccine in this cohort. METHODS: A total of 33
      subjects were recruited to the trial, all of whom were vaccinated. Serology was
      completed on samples taken at baseline and four weeks following vaccination to
      determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib
      polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses.
      RESULTS: At baseline, high proportions of subjects had protective antibody
      concentrations against MenC, Hib and tetanus due to previous vaccination and/or
      natural exposure. Vaccination induced > 3, 10 and 220 fold increases in geometric
      mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG,
      respectively. Following vaccination, 97% of subjects had putative protective SBA
      titres >= 8, 100% had short term protective anti-Hib PRP IgG concentrations >=
      0.15 MUg/mL and 97% had protective anti-tetanus toxoid concentrations >= 0.1
      IU/mL. No safety concerns were reported with minor local reactions being reported
      by 21% of subjects. CONCLUSIONS: Immunological responses determined in this trial
      are likely a combination of primary and secondary responses due to previous
      vaccination and natural exposure. Subjects were a representative cross-section of
      laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was
      safe and immunogenic in healthy adults providing the evidence that this vaccine
      may be used for providing protection in an occupational setting.

PMID- 25071862
TI  - Chemical and biological work-related risks across occupations in Europe: a
      review.
AB  - BACKGROUND: Work-related health inequalities are determined to some extent by an
      unequal exposure to chemical and biological risk factors of disease. Although
      their potential economic burden in the European Union (EU-25) might be
      substantial, comprehensive reviews focusing on the distribution of these risks
      across occupational groups are limited. Thus, the main objective of this review
      is to provide a synopsis of the exposure to chemical and biological hazards
      across occupational groups. In addition, main industrial applications of
      hazardous substances are identified and some epidemiological evidence is
      discussed regarding societal costs and incidence rates of work-related diseases.
      METHODS: Available lists of carcinogens, sensitisers, mutagens, reprotoxic
      substances and biological hazards were consulted. For each work-related hazard
      the main industrial application was identified in order to assess which ISCO
      occupational groups may be associated with direct exposure. Where available,
      information on annual tonnage production, risk assessment of the substances and
      pathogens, and other relevant data were collected and reported. RESULTS:
      Altogether 308 chemical and biological hazards were identified which may account
      to at least 693 direct exposures. These hazards concentrate on the following
      major occupational groups: technicians (ISCO 3), operators (ISCO 8), agricultural
      workers (ISCO 6) and workers in elementary occupations (ISCO 9). Common
      industrial applications associated with increased exposure rates relate among
      others to: (1) production or application of pigments, resins, cutting fluids,
      adhesives, pesticides and cleaning products, (2) production of rubber, plastics,
      textiles, pharmaceuticals and cosmetics, and (3) in agriculture, metallurgy and
      food processing industry, Societal costs of the unequal distribution of chemical
      and biological hazards across occupations depend on the corresponding work
      related diseases and may range from 2900 EUR to 126000 EUR per case/year.
      CONCLUSIONS: Risk of exposure to chemical and biological risks and work-related
      disease incidence are highly concentrated on four occupational groups. The
      unequal burden of exposure across occupations is an important contributing factor
      leading to health inequalities in society. The bulk of societal costs, however,
      are actually being borne by the workers themselves. There is an urgent need of
      taking into account the health impact of production processes and services on
      workers' health.

PMID- 25071863
TI  - Evaluation of coronal shift as an indicator of neuroaxial abnormalities in
      adolescent idiopathic scoliosis: a prospective study.
AB  - BACKGROUND: In previous studies, many indicator factors have been proposed to
      select patients who need an MRI screening of the spinal canal. In current study,
      the clinical and radiologic factors including coronal parameters of the curve
      were evaluated to find out which indicator is more important. METHODS: A
      prospective study included 143 consecutive patients with the diagnosis of
      adolescent idiopathic scoliosis who were treated between 2010 and 2013 at our
      spinal clinics. Only patients with normal or subtle neurologic findings were
      included. All patients were evaluated by a total spine MRI protocol for
      examination of neuroaxial abnormalities. Known indicators and also coronal shift
      were analysed in all patients with or without abnormal MRI. RESULTS: The
      incidence of neuroaxial abnormalities was 11.9% (17 of 143); only 5 patients
      (3.5%) were operated to treat their neuroaxial problem. The significant
      indicators of the abnormalities in our patients were: younger age at onset,
      asymmetric superficial abdominal reflex and, coronal shift more than 15 mm (P =
      0.03). Some previously known indicators like atypical curves, male gender, double
      curves and absence of thoracic lordosis were not different between two groups of
      the patients. CONCLUSIONS: A total spine MRI is recommended at presentation in
      patients with younger age, abnormal neurologic findings and severe coronal shift.

PMID- 25071864
TI  - Psychosis in an adolescent girl: a common manifestation in Niemann-Pick Type C
      disease.
AB  - Niemann-Pick disease type C (NP-C) is a rare autosomal-recessively inherited
      lysosomal storage disorder. It is caused by mutations in the NPC1 (95%) or NPC2
      gene. It is a progressive and highly heterogeneous disease, characterized by the
      presentation of visceral, neurological, and psychiatric symptoms. Apart from the
      patients that die early from organic failure, most of the patients with juvenile
      and adolescent/adult onset of the disease, develop neurological and psychiatric
      symptoms. In some cases psychiatric signs, mostly psychosis, can be the first
      sign of the disease. A delay in diagnosis is often seen. By describing the case
      of a 16-year old girl, we would like to highlight current opinion about NP-C
      disease and resume recent findings on the clinical presentation, diagnosis and
      treatment. We focus on the psychiatric signs, and most important the specific
      combinations that are typical for the disease. There is no curative treatment for
      NP-C. Miglustat is used to modify neurological signs in NP-C. 

PMID- 25071866
TI  - Molecular characterization of the rare translocation t(3;10)(q26;q21) in an acute
      myeloid leukemia patient.
AB  - BACKGROUND: In acute myeloid leukemia (AML), the MDS1 and EVI1 complex locus -
      MECOM, also known as the ecotropic virus integration site 1 - EVI1, located in
      band 3q26, can be rearranged with a variety of partner chromosomes and partner
      genes. Here we report on a 57-year-old female with AML who presented with the
      rare translocation t(3;10)(q26;q21) involving the MECOM gene. Our aim was to
      identify the fusion partner on chromosome 10q21 and to characterize the precise
      nucleotide sequence of the chromosomal breakpoint. METHODS: Cytogenetic and
      molecular-cytogenetic techniques, chromosome microdissection, next generation
      sequencing, long-range PCR and direct Sanger sequencing were used to map the
      chromosomal translocation. RESULTS: Using a combination of cytogenetic and
      molecular approaches, we mapped the t(3;10)(q26;q21) to the single nucleotide
      level, revealing a fusion of the MECOM gene (3q26.2) and C10orf107 (10q21.2).
      CONCLUSIONS: The approach described here opens up new possibilities in
      characterizing acquired as well as congenital chromosomal aberrations. In
      addition, DNA sequences of chromosomal breakpoints may be a useful tool for
      unique molecular minimal residual disease target identification in acute leukemia
      patients.

PMID- 25071865
TI  - Prevalence of child and adolescent psychiatric disorders in India: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The importance of epidemiological studies lies in recognition of
      cases that do not come to treatment settings. The increasing focus on child
      adolescent mental health in India points to the necessity of epidemiological
      studies on children. Although there are a few such studies done in different
      parts of India in different socio-cultural settings, data from those cannot be
      generalized to the entire country. This need can be served by meta-analysis.
      There has been no meta-analysis reported from India for the child and adolescent
      psychiatric epidemiology. AIM: To review and do the meta-analysis of
      epidemiological studies on child and adolescent psychiatric disorder from India.
      METHODS: Sixteen community based studies on 14594 children and adolescents; and
      seven school based studies on 5687 children and adolescents, reporting prevalence
      of child and adolescent psychiatric disorder were analyzed and overall prevalence
      was calculated. RESULTS: The prevalence rate of child and adolescent psychiatric
      disorders in the community has been found to be 6.46% (95% confidence interval
      6.08% - 6.88%) and in the school it has been found to be 23.33% (95% confidence
      interval 22.25% - 24.45%). CONCLUSIONS: This is the first meta-analysis
      determining the epidemiology of child and adolescent psychiatric disorders in
      India. It has been found that the reporting systems of psychiatric disorders in
      children are inadequate.

PMID- 25071867
TI  - Diverse convergent evidence in the genetic analysis of complex disease:
      coordinating omic, informatic, and experimental evidence to better identify and
      validate risk factors.
AB  - In omic research, such as genome wide association studies, researchers seek to
      repeat their results in other datasets to reduce false positive findings and thus
      provide evidence for the existence of true associations. Unfortunately this
      standard validation approach cannot completely eliminate false positive
      conclusions, and it can also mask many true associations that might otherwise
      advance our understanding of pathology. These issues beg the question: How can we
      increase the amount of knowledge gained from high throughput genetic data? To
      address this challenge, we present an approach that complements standard
      statistical validation methods by drawing attention to both potential false
      negative and false positive conclusions, as well as providing broad information
      for directing future research. The Diverse Convergent Evidence approach (DiCE) we
      propose integrates information from multiple sources (omics, informatics, and
      laboratory experiments) to estimate the strength of the available corroborating
      evidence supporting a given association. This process is designed to yield an
      evidence metric that has utility when etiologic heterogeneity, variable risk
      factor frequencies, and a variety of observational data imperfections might lead
      to false conclusions. We provide proof of principle examples in which DiCE
      identified strong evidence for associations that have established biological
      importance, when standard validation methods alone did not provide support. If
      used as an adjunct to standard validation methods this approach can leverage
      multiple distinct data types to improve genetic risk factor discovery/validation,
      promote effective science communication, and guide future research directions. 

PMID- 25071868
TI  - A mechanistic role for the chromatin modulator, NAP1L1, in pancreatic
      neuroendocrine neoplasm proliferation and metastases.
AB  - BACKGROUND: The chromatin remodeler NAP1L1, which is upregulated in small
      intestinal neuroendocrine neoplasms (NENs), has been implicated in cell cycle
      progression. As p57(Kip2) (CDKN1C), a negative regulator of proliferation and a
      tumor suppressor, is controlled by members of the NAP1 family, we tested the
      hypothesis that NAP1L1 may have a mechanistic role in regulating pancreatic NEN
      proliferation through regulation of p57(Kip2). RESULTS: NAP1L1 silencing (siRNA
      and shRNA/lipofectamine approach) decreased proliferation through inhibition of
      mechanistic (mammalian) target of rapamycin pathway proteins and their
      phosphorylation (p < 0.05) in the pancreatic neuroendocrine neoplasm cell line
      BON in vitro (p < 0.0001) and resulted in significantly smaller (p < 0.05) and
      lighter (p < 0.05) tumors in the orthotopic pancreatic NEN mouse model.
      Methylation of the p57 (Kip2) promoter was decreased by NAP1L1 silencing (p <
      0.05), and expression of p57(Kip2) (transcript and protein) was upregulated. For
      methylation of the p57 (Kip2) promoter, NAP1L1 bound directly to the promoter (
      164 to +21, chromatin immunoprecipitation). In 43 pancreatic NEN samples (38
      primaries and 5 metastasis), NAP1L1 was over-expressed in metastasis (p < 0.001),
      expression which was inversely correlated with p57(Kip2) (p < 0.01) on mRNA and
      protein levels. Menin was not differentially expressed. CONCLUSION: NAP1L1 is
      over-expressed in pancreatic neuroendocrine neoplasm metastases and
      epigenetically promotes cell proliferation through regulation of p57 (Kip2)
      promoter methylation.

PMID- 25071869
TI  - Biomineralization control related to population density under ocean
      acidification.
AB  - Anthropogenic CO2 is a major driver of current environmental change in most
      ecosystems1, and the related ocean acidification (OA) is threatening marine
      biota2. With increasing pCO2, calcification rates of several species decrease3,
      although cases of up-regulation are observed4. Here, we show that biological
      control over mineralization relates to species abundance along a natural pH
      gradient. As pCO2 increased, the mineralogy of a scleractinian coral
      (Balanophyllia europaea) and a mollusc (Vermetus triqueter) did not change. In
      contrast, two calcifying algae (Padina pavonica and Acetabularia acetabulum)
      reduced and changed mineralization with increasing pCO2, from aragonite to the
      less soluble calcium sulphates and whewellite, respectively. As pCO2 increased,
      the coral and mollusc abundance was severely reduced, with both species
      disappearing at pH < 7.8. Conversely, the two calcifying and a non-calcifying
      algae (Lobophora variegata) showed less severe or no reductions with increasing
      pCO2, and were all found at the lowest pH site. The mineralization response to
      decreasing pH suggests a link with the degree of control over the
      biomineralization process by the organism, as only species with lower control
      managed to thrive in the lowest pH.

PMID- 25071870
TI  - The role of antiproliferative gene Tob1 in the immune system.
AB  - Tob1 (transducer of ERBB2-1, TOB1 is humans) is a member of the antiproliferative
      (APRO) family of proteins that controls cell cycle progression in several cell
      types. In addition, Tob1 has been implicated in diverse cellular mechanisms such
      as embryonic dorsal development, and T helper 17 (Th17) cell function. More
      recently, evidence linking Tob1 function to experimental and human immune related
      disorders has mounted, thus underscoring the potential of this molecule as a
      biomarker and as a therapeutic target. This article reviews these functions with
      an emphasis on their implications for human autoimmune diseases such as multiple
      sclerosis.

PMID- 25071871
TI  - Developmental delay in Rett syndrome: data from the natural history study.
AB  - BACKGROUND: Early development appears normal in Rett syndrome (OMIM #312750) and
      may be more apparent than real. A major purpose of the Rett Syndrome (RTT)
      Natural History Study (NHS) was to examine achievement of developmental skills or
      abilities in classic and atypical RTT and assess phenotype-genotype relations in
      classic RTT. METHODS: Developmental skills in four realms, gross and fine motor,
      and receptive and expressive communication from initial enrollment and
      longitudinal assessments for up to 7 years, were assessed from 542 females
      meeting criteria for classic RTT and 96 females with atypical RTT divided into
      two groups: 50 with better and 46 with poorer functional scores. Data were
      analyzed for age at acquisition and loss of developmental features and for
      phenotype-genotype effects. Acquired, lost, and retained skills were compared
      between classic RTT and atypical RTT with better or poorer functional scores
      using Fisher's Exact test. To examine if the mean total score from the Motor
      Behavioral Assessment during follow-up differed for acquiring a skill, we used a
      generalized estimating equation assuming compound symmetry correlation structure
      within a subject. A general linear model was used to examine whether the mean age
      of acquisition or loss of a developmental skill differed by mutation type. P
      values <0.05 were considered significant and were two-sided without adjustment
      for multiple testing. Statistical analyses utilized SAS 9.3 (SAS Institute, Cary,
      NC, USA). RESULTS: Early developmental skills or abilities were often acquired
      albeit later than normal. More complex motor and communication acquisitions were
      delayed or absent. Clinical severity was less in those achieving the respective
      skill. Individuals with R133C, R294X, and R306C point mutations and 3'
      truncations tended to have better developmental outcomes. CONCLUSIONS: Early
      developmental skills were acquired by many, but clear differences from normal
      emerged, particularly in skills expected after age 6 months. When comparing
      clinical severity, greater acquisition of specific skills was associated with
      specific mutations, confirming the impression that these mutations confer milder
      developmental abnormalities. These data may serve for planning and interpretation
      of early intervention studies in RTT. TRIAL REGISTRATION: This NHS study,
      clinicaltrials.gov (NCT00296764), represents the largest group of RTT
      participants assessed repeatedly by direct examination.

PMID- 25071872
TI  - A pilot study on the diagnostic accuracy of proadrenomedullin and proatrial
      natriuretic Peptide in lower respiratory tract infections.
AB  - BACKGROUND: Pneumonia is the leading cause of death among infectious diseases in
      developed countries. However, the severity of pneumonia requiring hospitalization
      often makes the initial diagnosis difficult because of an equivocal clinical
      picture or interpretation of the chest film. The objective of the present study
      was to assess the usefulness of the plasma levels of mid-regional
      proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR
      proANP) in differentiating pneumonia from other lower respiratory tract
      infections (LRTIs). METHODS: A retrospective study was conducted. The plasma
      levels of MR-proADM and MR-proANP were measured in 85 patients hospitalized for
      LRTIs, 56 of whom with diagnosis of pneumonia and 29 with other LRTIs. RESULTS:
      The patients with pneumonia had increased MR-proADM levels (median 1.46 nmol/L
      [IQR 25-75, 0.82-2.02 nmol/L]) compared with the patients with other LRTIs
      (median 0.88 nmol/mL [0.71-1.39 nmol/L]) (p= 0.04). However, the MR-proANP levels
      did not show differences between the groups. The optimal threshold of MR-proADM
      to predict pneumonia was 1.5 nmol/L, which yielded a sensitivity of 51.7% (95%
      CI, 38.0-65.3), a 79.3% specificity (95% CI, 60.3-92.0), and an odds ratio of
      6.64 (95% CI, 1.32-32.85). The combination of this parameter with C-reactive
      protein in an "and" rule increased the specificity for detecting pneumonia
      significantly. CONCLUSION: MR-proADM levels (but not MR-proANP levels) are
      increased in patients with pneumonia although its discriminatory power is
      moderate.

PMID- 25071873
TI  - Nuclear imaging of amyloidosis.
AB  - Summary Amyloidosis is a clinical condition caused by deposition of various
      protein fibrills in extracellular space. The presented symptoms depend on the
      type of deposits and the organ or organs involved. The correct diagnosis is often
      difficult, due to lack of nonivasive imaging techniques and insufficiency of
      morphological imaging procedures delievered by radiology. We presented a list of
      potential radiopharmaceuticals that can be used in detecting various types of
      amyloidoses. (123)I-SAP proved to have high sensitivity in imaging of AA and AL
      amyloidosis in visceral organs. (99m)Tc-Aprotinin was found to be useful in
      detecting cardiac amyloidosis. A couple of classical radiotracers, such as
      (201)Tl, (123)I-mIBG, together with (111)In-antimyosin were also tested for
      accuracy in cardiac imaging, however the main problem was low specificity.
      Potential applicability was also found in case of some bone-seeking agents and
      other radiotracers, e.g. (67)Ga-citrate and (99m)Tc-penta-DMSA. High sensitivity
      and specificity was achieved with beta2-microglobulin labeled with (131)I or
      (111)In. Among PET tracers, (11)C-PIB deserves more attention, because it may
      have an important role in diagnosing of AD in the near future. Further clinical
      studies are expected to take place, because noninvasive diagnosing and monitoring
      of amyloidosis is still a challenge. 

PMID- 25071874
TI  - The Effect of Social Problem Solving Skills in the Relationship between Traumatic
      Stress and Moral Disengagement among Inner-City African American High School
      Students.
AB  - This study examined the relationship between traumatic stress, social problem
      solving, and moral disengagement among African American inner-city high school
      students. Participants consisted of 45 (25 males and 20 females) African American
      students enrolled in grades 10 through 12. Mediation was assessed by testing for
      the indirect effect using the confidence interval derived from 10,000
      bootstrapped resamples. The results revealed that social problem-solving skills
      have an indirect effect on the relationship between traumatic stress and moral
      disengagement. The findings suggest that African American youth that are
      negatively impacted by trauma evidence deficits in their social problem solving
      skills and are likely to be at an increased risk to morally disengage.
      Implications for culturally sensitive and trauma-based intervention programs are
      also provided.

PMID- 25071875
TI  - Informed consent in orthognathic surgery.
AB  - Historically, the patient-doctor relationship has been based on trust. Adequately
      informing a patient confirms this relationship and fulfills the legal obligation
      of the physician to inform the patient to the best of his knowledge. Informed
      consent is the process of providing patients with the realistic and necessary
      information in a manner which they can understand and recall and allows them
      voluntarily to make an informed choice on the treatment. In this article, the
      current knowledge about informed consent in orthognathic surgery is reviewed and
      discussed. 

PMID- 25071876
TI  - The Delay Phenomenon: A Compilation of Knowledge across Specialties.
AB  - Objective The purpose of this article is to review and integrate the available
      literature in different fields to gain a better understanding of the basic
      physiology and optimize vascular delay as a reconstructive surgery technique.
      Methods A broad search of the literature was performed using the Medline
      database. Two queries were performed using "vascular delay," a search expected to
      yield perspectives from the field of plastic and reconstructive surgery, and
      "ischemic preconditioning," (IPC) which was expected to yield research on the
      same topic in other fields. Results The combined searches yielded a total of 1824
      abstracts. The "vascular delay" query yielded 76 articles from 1984 to 2011. The
      "ischemic preconditioning" query yielded 6534 articles, ranging from 1980 to
      2012. The abstracts were screened for those from other specialties in addition to
      reconstructive surgery, analyzed potential or current uses of vascular delay in
      practice, or provided developments in understanding the pathophysiology of
      vascular delay. 70 articles were identified that met inclusion criteria and were
      applicable to vascular delay or ischemic preconditioning. Conclusion An
      understanding of IPC's implementation and mechanisms in other fields has
      beneficial implications for the field of reconstructive surgery in the context of
      the delay phenomenon. Despite an incomplete model of IPC's pathways, the anti
      oxidative, anti-apoptotic and anti-inflammatory benefits of IPC are well
      recognized. The activation of angiogenic genes through IPC could allow for
      complex flap design, even in poorly vascularized regions. IPC's promotion of
      angiogenesis and reduction of endothelial dysfunction remain most applicable to
      reconstructive surgery in reducing graft-related complications and flap failure. 

PMID- 25071877
TI  - Burden of maxillofacial trauma at level 1 trauma center.
AB  - There is an upward trend in facial injuries following changes in population
      pattern, increasing industrialization and urbanization, hence maxillofacial
      trauma is becoming a burden and a leading medical problem in emergency rooms
      worldwide. This study was performed to evaluate the pattern of maxillofacial
      fractures, associated injuries, and treatment used at Jai Prakash Narayan Apex
      Trauma Center (JPNATC), All India Institute of Medical Sciences (AIIMS), New
      Delhi, India, between January 2007 and June 2010. The study provides basis for
      establishment of trauma as major etiology of maxillofacial injuries and planning
      for preventive strategies. A retrospective study of patients seen and treated at
      JPNATC, AIIMS, New Delhi, between January 2007 and June 2010 was performed. Data
      extracted from patient records included etiology, age, sex, types and sites of
      fractures, treatment modality, and concomitant injuries. There were 795 fractures
      of the maxillofacial skeleton and 86 concomitant injuries from 542 patients. Road
      traffic accident (RTA) (56.8%) was the most common etiologic factor, followed by
      falls (22.3%) and fights (18.5%). The age range was from 3 to 75 years (mean,
      34.7 years) with a peak incidence in the third decade with a male-to-female ratio
      of 3.7:1. The most common location of maxillofacial fractures was the mandible
      615 (77%) and middle third 180 (23%). With regard to mandibular fractures, the
      body (29.6%) was the most common site, followed by the angle (24.4%), ramus
      (19.5%), dentoalveolar (14.6%), symphysis (11.0%), condyle (0.8%) while in the
      middle third, the nasal bone (36.7%) was the most common, followed by zygomatic
      bone (27.8), Lefort II (14.4), Lefort I (7.8%), dentoalveolar (10.0%), and Lefort
      III (3.3%). Majority of the patients were treated by open reduction and internal
      fixation (70.6). Concomitant injuries were 84 (10.8%) with orthopedic injuries
      accounting for the majority (63.9%). Head injury was associated in 16.3% of
      cases. RTA was the major etiologic factor of maxillofacial injuries in our
      setting and the young adult males were the main victims. Henceforth,
      establishment of regionalized, efficient, and focused trauma centers in various
      parts of the country particularly for acute trauma should be emphasized. Also,
      the laws regarding the precautions such as seat belts, speed limits, and traffic
      rules must be observed strictly to reduce the incidence of RTA. 

PMID- 25071878
TI  - Bridging Solutions in Dose Finding Problems.
AB  - The idea of bridging in dose-finding studies is closely linked to the problem of
      group heterogeneity. There are some distinctive features in the case of bridging
      which need to be considered if efficient estimation of the maximum tolerated dose
      (MTD) is to be accomplished. The case of two distinct populations is considered.
      In the bridging setting we usually have in mind two studies, corresponding to the
      two populations. In some cases, the first of these studies may have been
      completed while the second has yet to be initiated. In other cases, the studies
      take place simultaneously and information can then be shared among the two
      groups. The methodological problem is how to make most use of the information
      gained in the first study to help improve efficiency in the second. We describe
      the models that we can use for the purpose of bridging and study situations in
      which their use leads to overall improvements in performance as well as cases
      where there is no gain when compared to carrying out parallel studies.
      Simulations and an example in pediatric oncology help to provide further insight.

PMID- 25071879
TI  - FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC.
AB  - Over recent years, [18F]-fluorodeoxyglucose positron emission tomography acquired
      together with low dose computed tomography (FDG-PET/CT) has proven its role as a
      staging modality in patients with non-small cell lung cancer (NSCLC). The purpose
      of this review was to present the evidence to use FDG-PET/CT for response
      evaluation in patients with NSCLC, treated with epidermal growth factor receptor
      (EGFR)-tyrosine kinase inhibitors (TKI). All published articles from 1 November
      2003 to 1 November 2013 reporting on 18F-FDG-PET response evaluation during EGFR
      TKI treatment in patients with NSCLC were collected. In total 7 studies,
      including data of 210 patients were eligible for analyses. Our report shows that
      FDG-PET/CT response during EGFR-TKI therapy has potential in targeted treatment
      for NSCLC. FDG-PET/CT response is associated with clinical and radiologic
      response and with survival. Furthermore FDG-PET/CT response monitoring can be
      performed as early as 1-2 wk after initiation of EGFR-TKI treatment. Patients
      with substantial decrease of metabolic activity during EGFR-TKI treatment will
      probably benefit from continued treatment. If metabolic response does not occur
      within the first weeks of EGFR-TKI treatment, patients may be spared (further)
      unnecessary toxicity of ineffective treatment. Refining FDG-PET response criteria
      may help the clinician to decide on continuation or discontinuation of targeted
      treatment. 

PMID- 25071880
TI  - Coronary venous system in cardiac computer tomography: Visualization,
      classification and role.
AB  - The role of the coronary venous system was underestimated for many years. In the
      last 20 years, a few percutaneous cardiology techniques in which the anatomy of
      the coronary venous system was significant were developed and are in use. The
      most important seems to be cardiac resynchronization therapy, which is an
      invasive method for the treatment of heart failure. Unfortunately, one of the
      major problems is the significant anatomical variability of the coronary venous
      system. The description of the selected anatomical structures is only useful in
      selected cases such as, for example, the obstruction of selected vessels, a huge
      Thebesian valve, etc. The 3D images can add significant value; however, their
      usefulness is limited due to the different points of view that are obtained
      during intra-operational fluoroscopy. After summarizing all of the articles and
      guidelines, it can be recommended that the visualization of the coronary venous
      system be performed in certain patients before cardiac resynchronization. The
      best option is to use tomography with retrospective gating with the optimal
      reconstruction of cardiac veins that occurs during the diastolic phases. 

PMID- 25071881
TI  - Clinical significance of visceral adiposity assessed by computed tomography: A
      Japanese perspective.
AB  - Abdominal obesity, rather than total amount of fat, is linked to obesity-related
      disorders. Visceral adiposity is an important component of obesity-related
      disorders in Japanese individuals with a mild degree of adiposity compared with
      Western subjects. In 1983, our group reported techniques for body fat analysis
      using computed tomography (CT) and established the concept of visceral fat
      obesity in which intra-abdominal fat accumulation is an important factor in the
      development of obesity-related complications, such as diabetes, lipid disorders,
      hypertension and atherosclerosis. Our group also established ideal imaging
      conditions for determining abdominal fat area at the umbilical level CT scan.
      Visceral fat area (VFA) measured in a single slice at L4 level correlated
      significantly with the total abdominal visceral fat volume measured on multislice
      CT scan. In a large-scale study of a Japanese population, the mean number of
      obesity-related cardiovascular risk factors (hypertension, low high-density
      lipoprotein cholesterolemia and/or hypertriglyceridemia, and hyperglycemia) was
      greater than 1.0 at 100 cm(2) of VFA, irrespective of gender, age and body mass
      index. Our group also demonstrated that reduction of visceral fat accumulation
      subsequent to voluntary lifestyle modification, "Hokenshido", correlated with a
      decrease in the number of obesity-related cardiovascular risk factors. It is
      important to select the most appropriate subjects from the general population
      (e.g., non-obese subjects with a cluster of risk factors for the metabolic
      syndrome) that are most suitable for body weight reduction, with the goal of
      preventing atherosclerotic cardiovascular diseases. 

PMID- 25071882
TI  - Clinical significance of computed tomography assessment for third molar surgery.
AB  - Surgical extraction of the third molar is the most commonly performed surgical
      procedure in the clinical practice of oral surgery. Third molar surgery is
      warranted when there is inadequate space for eruption, malpositioning, or risk
      for cyst or odontogenic tumor formation. Preoperative assessment should include a
      detailed morphologic analysis of the third molar and its relationship to adjacent
      structures and surrounding tissues. Due to developments in medical engineering
      technology, computed tomography (CT) now plays a critical role in providing the
      clear images required for adequate assessment prior to third molar surgery.
      Removal of the maxillary third molar is associated with a risk for maxillary
      sinus perforation, whereas removal of the mandibular third molar can put patients
      at risk for a neurosensory deficit from damage to the lingual nerve or inferior
      alveolar nerve. Multiple factors, including demographic, anatomic, and treatment
      related factors, influence the incidence of nerve injury during or following
      removal of the third molar. CT assessment of the third molar prior to surgery can
      identify some of these risk factors, such as the absence of cortication between
      the mandibular third molar and the inferior alveolar canal, prior to surgery to
      reduce the risk for nerve damage. This topic highlight presents an overview of
      the clinical significance of CT assessment in third molar surgery. 

PMID- 25071883
TI  - Magnetic resonance cholangiography in the assessment and management of biliary
      complications after OLT.
AB  - Despite advances in patient and graft management, biliary complications (BC)
      still represent a challenge both in the early and delayed period after orthotopic
      liver transplantation (OLT). Because of unspecific clinical presentation, imaging
      is often mandatory in order to diagnose BC. Among imaging modalities, magnetic
      resonance cholangiography (MRC) has gained widespread acceptance as a tool to
      represent the reconstructed biliary tree noninvasively, using both the
      conventional technique (based on heavily T2-weighted sequences) and contrast
      enhanced MRC (based on the acquisition of T1-weighted sequences after the
      administration of hepatobiliary contrast agents). On this basis, MRC is generally
      indicated to: (1) avoid unnecessary procedures of direct cholangiography in
      patients with a negative examination and/or identify alternative complications;
      and (2) provide a road map for interventional procedures or surgery. As
      illustrated in the review, MRC is accurate in the diagnosis of different types of
      biliary complications, including anastomotic strictures, non-anastomotic
      strictures, leakage and stones. 

PMID- 25071884
TI  - Recent developments in optimal experimental designs for functional magnetic
      resonance imaging.
AB  - Functional magnetic resonance imaging (fMRI) is one of the leading brain mapping
      technologies for studying brain activity in response to mental stimuli. For
      neuroimaging studies utilizing this pioneering technology, there is a great
      demand of high-quality experimental designs that help to collect informative data
      to make precise and valid inference about brain functions. This paper provides a
      survey on recent developments in experimental designs for fMRI studies. We
      briefly introduce some analytical and computational tools for obtaining good
      designs based on a specified design selection criterion. Research results about
      some commonly considered designs such as blocked designs, and m-sequences are
      also discussed. Moreover, we present a recently proposed new type of fMRI designs
      that can be constructed using a certain type of Hadamard matrices. Under certain
      assumptions, these designs can be shown to be statistically optimal. Some future
      research directions in design of fMRI experiments are also discussed. 

PMID- 25071885
TI  - Nuclear medicine and the failed joint replacement: Past, present, and future.
AB  - Soon after the introduction of the modern prosthetic joint, it was recognized
      that radionuclide imaging provides useful information about these devices. The
      bone scan was used extensively to identify causes of prosthetic joint failure. It
      became apparent, however, that although sensitive, regardless of how the images
      were analyzed or how it was performed, the test was not specific and could not
      distinguish among the causes of prosthetic failure. Advances in anatomic imaging,
      notably cross sectional modalities, have facilitated the diagnosis of many, if
      not most, causes of prosthetic failure, with the important exception of
      infection. This has led to a shift in the diagnostic paradigm, in which nuclear
      medicine investigations increasingly have focused on diagnosing infection. The
      recognition that bone scintigraphy could not reliably diagnose infection led to
      the development of combined studies, first bone/gallium and subsequently
      leukocyte/bone and leukocyte/marrow imaging. Labeled leukocyte imaging, combined
      with bone marrow imaging is the most accurate (about 90%) imaging test for
      diagnosing joint arthroplasty infection. Its value not withstanding, there are
      significant disadvantages to this test. In-vivo techniques for labeling
      leukocytes, using antigranulocyte antibodies have been explored, but have their
      own limitations and the results have been inconsistent. Fluorodeoxyglucose (FDG)
      positron emission tomography (FDG-PET) has been extensively investigated for more
      than a decade but its role in diagnosing the infected prosthesis has yet to be
      established. Antimicrobial peptides bind to bacterial cell membranes and are
      infection specific. Data suggest that these agents may be useful for diagnosing
      prosthetic joint infection, but large scale studies have yet to be undertaken.
      Although for many years nuclear medicine has focused on diagnosing prosthetic
      joint infection, the advent of hybrid imaging with single-photon emission
      computed tomography(SPECT)/electronic computer X-ray tomography technique (CT)
      and the availability of fluorine-18 fluoride PET suggests that the diagnostic
      paradigm may be shifting again. By providing the anatomic information lacking in
      conventional radionuclide studies, there is renewed interest in bone
      scintigraphy, performed as a SPECT/CT procedure, for detecting joint instability,
      mechanical loosening and component malpositioning. Fluoride-PET may provide new
      insights into periprosthetic bone metabolism. The objective of this manuscript is
      to provide a comprehensive review of the evolution of nuclear medicine imaging of
      joint replacements. 

PMID- 25071886
TI  - Echographic imaging of tumoral cells through novel nanosystems for image
      diagnosis.
AB  - Since the recognition of disease molecular basis, it has become clear that the
      keystone moments of medical practice, namely early diagnosis, appropriate
      therapeutic treatment and patient follow-up, must be approached at a molecular
      level. These objectives will be in the near future more effectively achievable
      thanks to the impressive developments in nanotechnologies and their applications
      to the biomedical field, starting-up the nanomedicine era. The continuous
      advances in the development of biocompatible smart nanomaterials, in particular,
      will be crucial in several aspects of medicine. In fact, the possibility of
      manufacturing nanoparticle contrast agents that can be selectively targeted to
      specific pathological cells has extended molecular imaging applications to non
      ionizing techniques and, at the same time, has made reachable the perspective of
      combining highly accurate diagnoses and personalized therapies in a single
      theranostic intervention. Main developing applications of nanosized theranostic
      agents include targeted molecular imaging, controlled drug release, therapeutic
      monitoring, guidance of radiation-based treatments and surgical interventions.
      Here we will review the most recent findings in nanoparticles contrast agents and
      their applications in the field of cancer molecular imaging employing non
      ionizing techniques and disease-specific contrast agents, with special focus on
      recent findings on those nanomaterials particularly promising for ultrasound
      molecular imaging and simultaneous treatment of cancer. 

PMID- 25071887
TI  - Neural mechanisms of mindfulness and meditation: Evidence from neuroimaging
      studies.
AB  - Mindfulness is the dispassionate, moment-by-moment awareness of sensations,
      emotions and thoughts. Mindfulness-based interventions are being increasingly
      used for stress, psychological well being, coping with chronic illness as well as
      adjunctive treatments for psychiatric disorders. However, the neural mechanisms
      associated with mindfulness have not been well characterized. Recent functional
      and structural neuroimaging studies are beginning to provide insights into neural
      processes associated with the practice of mindfulness. A review of this
      literature revealed compelling evidence that mindfulness impacts the function of
      the medial cortex and associated default mode network as well as insula and
      amygdala. Additionally, mindfulness practice appears to effect lateral frontal
      regions and basal ganglia, at least in some cases. Structural imaging studies are
      consistent with these findings and also indicate changes in the hippocampus.
      While many questions remain unanswered, the current literature provides evidence
      of brain regions and networks relevant for understanding neural processes
      associated with mindfulness. 

PMID- 25071888
TI  - Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters.
AB  - Various single or multi-modality therapeutic options are available to treat pain
      of bone metastasis in patients with prostate cancer. Different radionuclides that
      emit beta-rays such as (153)Samarium and (89)Strontium and achieve palliation are
      commercially available. In contrast to beta-emitters, (223)Radium as a alpha
      emitter has a short path-length. The advantage of the alpha-emitter is thus a
      highly localized biological effect that is caused by radiation induced DNA double
      strand breaks and subsequent cell killing and/or limited effectiveness of
      cellular repair mechanisms. Due to the limited range of the alpha-particles the
      bone surface to red bone marrow dose ratio is also lower for (223)Radium which is
      expressed in a lower myelotoxicity. The alpha emitter (223)Radium dichloride is
      the first radiopharmaceutical that significantly prolongs life in castrate
      resistant prostate cancer patients with wide-spread bone metastatic disease. In a
      phase III, randomized, double-blind, placebo-controlled study 921 patients with
      castration-resistant prostate cancer and bone metastases were randomly assigned.
      The analysis confirmed the (223)Radium survival benefit compared to the placebo
      (median, 14.9 mo vs 11.3 mo; P < 0.001). In addition, the treatment results in
      pain palliation and thus, improved quality of life and a delay of skeletal
      related events. At the same time the toxicity profile of (223)Radium was
      favourable. Since May 2013, (223)Radium dichloride (Xofigo((r))) is approved by
      the US Food and Drug Administration. 

PMID- 25071889
TI  - Nuclear imaging in detection and monitoring of cardiotoxicity.
AB  - Cardiotoxicity as a result of cancer treatment is a novel and serious public
      health issue that has a significant impact on a cancer patient's management and
      outcome. The coexistence of cancer and cardiac disease in the same patient is
      more common because of aging population and improvements in the efficacy of
      antitumor agents. Left ventricular dysfunction is the most typical manifestation
      and can lead to heart failure. Left ventricular ejection fraction measurement by
      echocardiography and multigated radionuclide angiography is the most common
      diagnostic approach to detect cardiac damage, but it identifies a late
      manifestation of myocardial injury. Early non-invasive imaging techniques are
      needed for the diagnosis and monitoring of cardiotoxic effects. Although
      echocardiography and cardiac magnetic resonance are the most commonly used
      imaging techniques for cardiotoxicity assessment, greater attention is focused on
      new nuclear cardiologic techniques, which can identify high-risk patients in the
      early stage and visualize the pathophysiologic process at the tissue level before
      clinical manifestation. The aim of this review is to summarize the role of
      nuclear imaging techniques in the non-invasive detection of myocardial damage
      related to antineoplastic therapy at the reversible stage, focusing on the
      current role and future perspectives of nuclear imaging techniques and molecular
      radiotracers in detection and monitoring of cardiotoxicity. 

PMID- 25071890
TI  - Nuclear imaging to characterize adrenal tumors: Comparison with MRI.
AB  - AIM: To describe the role of nuclear imaging modalities using nor-cholesterol,
      metaiodobenzylguanidine (MIBG) and fluorine-deoxy-glucose (FDG) in adrenal tumors
      for lesion characterization in comparison with magnetic resonance (MR). METHODS:
      Population was classified in group 1 consisting of 30 patients with non
      hypersecreting unilateral adrenal masses, in group 2 consisting of 34 patients
      with hypersecreting (n = 19) or non-hypersecreting (n = 15) adrenal adenomas and
      in group 3 consisting of 18 patients with chromaffin-tissue tumors (CTT), of
      which 14 were pheochromocytomas while 4 were paragangliomas (n = 4). All patients
      underwent MR and nuclear studies (nor-cholesterol, MIBG and FDG). Pathology
      samples (n = 63) or follow-up data in adenomas (n = 19) were used as standard of
      reference for imaging studies interpretation. RESULTS: In group 1, MR findings
      were not highly accurate for lesion characterization, while the results of
      nuclear scans showed abnormal nor-cholesterol, MIBG and FDG concentration in all
      cases of adenomas, pheos and malignant tumors, respectively. In group 2, no
      differences in MR parameters were found between hyperfunctioning and non
      hyperfunctioning adenomas, while nor-cholesterol uptake was significantly higher
      in hyperfunctioning compared to non-hyperfunctioning lesions. In group 3, no
      differences in MR parameters were found between benign and malignant CCT, while
      MIBG uptake was significantly higher in malignant compared to benign tumors.
      CONCLUSION: On the basis of our findings, nuclear imaging modalities using
      specific target agents are able to better characterize adrenal tumors, compared
      with MR. In particular, radionuclide techniques are able to identify the nature
      of adrenal incidentalomas and to differentiate between hypersecreting and non
      hypersecreting adenomas as well as between benign and malignant CTT.

PMID- 25071891
TI  - Usefulness of myocardial positron emission tomography/nuclear imaging in
      Takotsubo cardiomyopathy.
AB  - AIM: To analyse and summarize all the articles related to positron emission
      tomography and Takotsubo cardiomyopathy (TTC). METHODS: We performed a systematic
      review of the existing literature on positron emission tomography/nuclear imaging
      and Takotsubo cardiomyopathy using PUBMED database. We combined search terms such
      as "takotsubo", "takotsubo syndrome", "myocardial positron emission tomography",
      "positron emission tomography". All case reports were excluded. The list included
      only four articles which were reviewed by two independent investigators. It was
      not possible to undertake a formal meta-analysis because of the heterogeneity of
      the studies; therefore, we made a narrative synthesis of the collected data.
      RESULTS: Nuclear medicine techniques can be useful employed in the differential
      diagnosis of TTC from an acute coronary syndrome (ACS). In fact, transient left
      ventricular (LV) apical ballooning is a syndrome frequently misdiagnosed as an
      ACS and can mimic symptoms of myocardial infarction with ST-T segments changes on
      electrocardiography (ECG), a limited release of myocardial enzyme, mainly
      reported after sudden emotional or physical stress, and an akinesis or dyskinesis
      of the left ventricle apex which are completely reversible in a few weeks. In the
      studies included in this review, nuclear medicine techniques have demonstrated a
      discrepancy between normal perfusion and a reduced glucose utilization in TTC,
      commonly known as "inverse flow metabolism mismatch". This suggests that apical
      ballooning represents a transient metabolic disorder on the cellular level,
      rather than a structural contractile disease of the myocardium, due to a
      transient decrease of glucose metabolism that might be related to a coronary
      microcirculation impairment followed by prolonged myocardial stunning.
      CONCLUSION: Nuclear medicine techniques can be usefully used for the diagnosis of
      TTC and can increase our knowledge of the pathophysiological mechanisms of TTC.

PMID- 25071892
TI  - Bilateral squamosal suture synostosis: A rare form of isolated craniosynostosis
      in Crouzon syndrome.
AB  - Craniosynostosis is a pathologic condition which is characterized by the
      premature fusion of cranial sutures. It may occur alone or in association with
      other anomalies making up various syndromes. Crouzon syndrome is the most common
      craniosynostosis syndrome. Bicoronal sutures fusion is most commonly involved in
      Crouzon syndrome. There have only been a handful of cases of squamosal suture
      synostosis described in the surgery literature with the few ones described in
      Crouzon syndrome associated with other types of craniosynostosis. To the best of
      our knowledge, we are presenting the first case of isolated bilateral squamosal
      suture synostosis in a patient with Crouzon syndrome in a radiology journal with
      emphasis on its radiological appearance. 

PMID- 25071893
TI  - Aicardi syndrome: Neonatal diagnosis by means of transfontanellar ultrasound.
AB  - Aicardi syndrome is a rare genetic disease characterized by a characteristic
      classical trio of neurological clinical abnormalities (spasms), agenesis of the
      corpus callosum and ophthalmological abnormalities (chorioretinal lacunae). The
      diagnosis can be suspected by prenatal ultrasound with color Doppler identifying
      the agenesis of the corpus callosum. Usually, the diagnosis is confirmed in the
      neonate period by transfontanellar ultrasound and ophthalmological examination.
      We present a case of newborn with Aicardi syndrome, being the transfontanellar
      identified partial dysgenesis of the corpus callosum and a cyst in the inter
      hemispheric fissure. Ophthalmological examination showed bilateral chorioretinal
      lacunae. 

PMID- 25071894
TI  - Differentiation of true anophthalmia from clinical anophthalmia using
      neuroradiological imaging.
AB  - Anophthalmia is a condition of the absence of an eye and the presence of a small
      eye within the orbit. It is associated with many known syndromes. Clinical
      findings, as well as imaging modalities and genetic analysis, are important in
      making the diagnosis. Imaging modalities are crucial scanning methods.
      Cryptophthalmos, cyclopia, synophthalmia and congenital cystic eye should be
      considered in differential diagnoses. We report two clinical anophthalmic
      siblings, emphasizing the importance of neuroradiological and orbital imaging
      findings in distinguishing true congenital anophthalmia from clinical
      anophthalmia. 

PMID- 25071895
TI  - Does radiation exposure from abdominal computed tomography increase cancer risk
      in patients with inflammatory bowel disease and Behcet disease?

PMID- 25071896
TI  - Hepatitis C viral kinetics as a determinant of stopping pegylated interferon and
      ribavirin in genotype 1 infection.

PMID- 25071897
TI  - Regional diversity of hepatitis C virus prevalence: seeking for culture specific
      mode of transmission.

PMID- 25071898
TI  - Endoscopic papillary large balloon dilation: it is about time we did for a
      whopper.

PMID- 25071899
TI  - Endoscopic ultrasound-guided transluminal drainage for peripancreatic fluid
      collections: where are we now?
AB  - Endoscopic drainage for pancreatic and peripancreatic fluid collections (PFCs)
      has been increasingly used as a minimally invasive alternative to surgical or
      percutaneous drainage. Recently, endoscopic ultrasound-guided transluminal
      drainage (EUS-TD) has become the standard of care and a safe procedure for
      nonsurgical PFC treatment. EUS-TD ensures a safe puncture, avoiding intervening
      blood vessels. Single or multiple plastic stents (combined with a nasocystic
      catheter) were used for the treatment of PFCs for EUS-TD. More recently, the use
      of covered self-expandable metallic stents (CSEMSs) has provided a safer and more
      efficient approach route for internal drainage. We focused our review on the best
      approach and stent to use in endoscopic drainage for PFCs. We reviewed studies of
      EUS-TD for PFCs based on the original Atlanta Classification, including case
      reports, case series, and previous review articles. Data on clinical outcomes and
      adverse events were collected retrospectively. A total of 93 patients underwent
      EUS-TD of pancreatic pseudocysts using CSEMSs. The treatment success and adverse
      event rates were 94.6% and 21.1%, respectively. The majority of complications
      were of mild severity and resolved with conservative therapy. A total of 56
      patients underwent EUS-TD using CSEMSs for pancreatic abscesses or infected
      walled-off necroses. The treatment success and adverse event rates were 87.8% and
      9.5%, respectively. EUS-TD can be performed safely and efficiently for PFC
      treatment. Larger diameter CSEMSs without additional fistula tract dilation for
      the passage of a standard scope are needed to access and drain for PFCs with
      solid debris. 

PMID- 25071901
TI  - Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory
      drug-induced mucosal toxicity.
AB  - BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to
      prevent the gastrointestinal complications of nonsteroidal anti-inflammatory
      drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of
      prostaglandins and to eliminate free oxygen radicals, thus enhancing the
      protective function of the gastric mucosa. However, it is unknown whether
      rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this
      study was to determine the effectiveness of rebamipide compared to misoprostol in
      preventing NSAID-induced gastrointestinal complications in patients requiring
      continuous NSAID treatment. METHODS: We studied 479 patients who required
      continuous NSAID treatment. The patients were randomly assigned to groups that
      received 100 mg of rebamipide three times per day or 200 MUg of misoprostol three
      times per day for 12 weeks. The primary endpoint of the analysis was the
      occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of
      therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and
      237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the
      misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group.
      There was a significant difference in withdrawal rate between the two groups
      (p=0.0103). The per protocol analysis set was not valid because of the dropout
      rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is
      the main set for the efficacy analysis in this study. After 12 weeks, the
      occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol
      groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the
      therapeutic failure rate was similar in the rebamipide and misoprostol groups
      (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal
      symptoms was significantly lower in the rebamipide group than in the misoprostol
      group (p=0.0002). The amount of antacid used was significantly lower in the
      rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS:
      Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the
      gastrointestinal symptoms associated with NSAID administration. When the
      possibility of poor compliance and the potential adverse effects of misoprostol
      are considered, rebamipide appears to be a clinically effective and safe
      alternative.

PMID- 25071900
TI  - Barrett's esophagus and cancer risk: how research advances can impact clinical
      practice.
AB  - Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma
      (EAC), whose incidence has increased sharply in the last 4 decades. The annual
      conversion rate of BE to cancer is significant, but small. The identification of
      patients at a higher risk of cancer therefore poses a clinical conundrum.
      Currently, endoscopic surveillance is recommended in BE patients, with the aim of
      diagnosing either dysplasia or cancer at early stages, both of which are curable
      with minimally invasive endoscopic techniques. There is a large variation in
      clinical practice for endoscopic surveillance, and dysplasia as a marker of
      increased risk is affected by sampling error and high interobserver variability.
      Screening programs have not yet been formally accepted, mainly due to the
      economic burden that would be generated by upper gastrointestinal endoscopy.
      Screening programs have not yet been formally accepted, mainly due to the
      economic burden that would be generated by widespread indication to upper
      gastrointestinal endoscopy. In fact, it is currently difficult to formulate an
      accurate algorithm to confidently target the population at risk, based on the
      known clinical risk factors for BE and EAC. This review will focus on the
      clinical and molecular factors that are involved in the development of BE and its
      conversion to cancer and on how increased knowledge in these areas can improve
      the clinical management of the disease. 

PMID- 25071902
TI  - Radiation exposure from abdominal imaging studies in patients with intestinal
      Behcet disease.
AB  - BACKGROUND/AIMS: Recently, several studies have revealed that diagnostic imaging
      can result in exposure to harmful levels of ionizing radiation in inflammatory
      bowel disease patients. However, the extent of radiation exposure in intestinal
      Behcet disease (BD) patients has not been documented. The aim of this study was
      to estimate the radiation exposure from abdominal imaging studies in intestinal
      BD patients. METHODS: Patients with a diagnosis of intestinal BD established
      between January 1990 and March 2012 were investigated at a single tertiary
      academic medical center. The cumulative effective dose (CED) was calculated
      retrospectively from standard tables and by counting the number of abdominal
      imaging studies performed. High exposure was defined as CED >50 mSv. RESULTS: In
      total, 270 patients were included in the study. The mean CED was 41.3 mSv, and
      28.1% of patients were exposed to high levels of radiation. Computed tomography
      (CT) accounted for 81.7% of the total effective dose. In multivariate analyses,
      predictors of high radiation exposure were azathioprine/6-mercaptopurine use,
      surgery, and hospitalization. CONCLUSIONS: Approximately a quarter of intestinal
      BD patients were exposed to harmful levels of diagnostic radiation, mainly from
      CT examination. Clinicians should reduce the number of unnecessary CT
      examinations and consider low-dose CT profiles or alternative modalities such as
      magnetic resonance enterography.

PMID- 25071903
TI  - Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a
      rat model.
AB  - BACKGROUND/AIMS: DA-9701 is a newly developed drug made from the vegetal extracts
      of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate
      the effect of DA-9701 on colorectal distension (CRD)-induced visceral
      hypersensitivity in a rat model. METHODS: Male Sprague-Dawley rats were subjected
      to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At
      6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm
      Hg, and changes in the mean arterial pressure (MAP) were measured at baseline
      (i.e., without any drug administration) and after the administration of different
      doses of DA-9701. RESULTS: In the absence of DA-9701, the MAP changes after CRD
      were significantly higher in the CI group than in the control group at all
      applied pressures. In the control group, MAP changes after CRD were not
      significantly affected by the administration of DA-9701. In the CI group,
      however, the administration of DA-9701 resulted in a significant decrease in MAP
      changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced
      a more significant decrease in MAP changes than the 0.3 mg/kg dose. CONCLUSIONS:
      The administration of DA-9701 resulted in a significant increase in pain
      threshold in rats with CRD-induced visceral hypersensitivity.

PMID- 25071904
TI  - Endoscopy-guided balloon dilation of benign anastomotic strictures after radical
      gastrectomy for gastric cancer.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the outcome of endoscopic
      dilation for benign anastomotic stricture after radical gastrectomy in gastric
      cancer patients. METHODS: Gastric cancer patients who underwent endoscopic
      balloon dilation for benign anastomosis stricture after radical gastrectomy
      during a 6-year period were reviewed retrospectively. RESULTS: Twenty-one
      patients developed benign strictures at the site of anastomosis. The majority of
      strictures occurred within 1 year after surgery (95.2%). The median duration to
      stenosis after surgery was 1.70 months (range, 0.17 to 23.97 months). The success
      rate of the first endoscopic dilation was 61.9%. Between the restenosis group
      (n=8) and the no restenosis group (n=13), there were no significant differences
      in the body mass index (22.82 kg/m(2) vs 22.46 kg/m(2)), interval to symptom
      onset (73.9 days vs 109.3 days), interval to treatment (84.6 days vs 115.6 days),
      maximal balloon diameter (14.12 mm vs 15.62 mm), number of balloon dilation
      sessions (1.75 vs 1.31), location of gastric cancer or type of surgery. One
      patient required surgery because of stricture refractory to repeated dilation.
      CONCLUSIONS: Endoscopic dilation is a highly effective treatment for benign
      anastomotic strictures after radical gastrectomy for gastric cancer and should be
      considered a primary intervention prior to proceeding with surgical revision.

PMID- 25071905
TI  - Clinical outcomes associated with treatment modalities for gastrointestinal
      bezoars.
AB  - BACKGROUND/AIMS: With technical and instrumental advances, the endoscopic removal
      of bezoars is now more common than conventional surgical removal. We investigated
      the clinical outcomes in a patient cohort with gastrointestinal bezoars removed
      using different treatment modalities. METHODS: Between June 1989 and March 2012,
      93 patients with gastrointestinal bezoars underwent endoscopic or surgical
      procedures at the Asan Medical Center. These patients were divided into
      endoscopic (n=39) and surgical (n=54) treatment groups in accordance with the
      initial treatment modality. The clinical feature and outcomes of these two groups
      were analyzed retrospectively. RESULTS: The median follow-up period was 13 months
      (interquartile range [IQR], 0 to 77 months) in 93 patients with a median age of
      60 years (IQR, 50 to 73 years). Among the initial symptoms, abdominal pain was
      the most common chief complaint (72.1%). The bezoars were commonly located in the
      stomach (82.1%) in the endoscopic treatment group and in the small bowel (66.7%)
      in the surgical treatment group. The success rates of endoscopic and surgical
      treatment were 89.7% and 98.1%, and the complication rates were 12.8% and 33.3%,
      respectively. CONCLUSIONS: Endoscopic removal of a gastrointestinal bezoar is an
      effective treatment modality; however, surgical removal is needed in some cases.

PMID- 25071906
TI  - Treatment outcome for gastric mucosa-associated lymphoid tissue lymphoma
      according to Helicobacter pylori infection status: a single-center experience.
AB  - BACKGROUND/AIMS: Helicobacter pylori eradication therapy has been used as a first
      line treatment for H. pylori-positive gastric mucosa-associated lymphoid tissue
      (MALT) lymphoma. However, the management strategy for H. pylori-negative MALT
      lymphoma remains controversial. Therefore, the aim of this study was to examine
      the success rate of each treatment option for H. pylori-positive and H. pylori
      negative gastric MALT lymphomas. METHODS: In total, 57 patients with gastric MALT
      lymphoma diagnosed between December 2000 and June 2012 were enrolled in the
      study. The treatment responses were compared between H. pylori-positive and H.
      pylori-negative gastric MALT lymphomas. RESULTS: Of the 57 patients, 43 (75%) had
      H. pylori infection. Forty-eight patients received H. pylori eradication as a
      first-line treatment, and complete remission was achieved in 31 of the 39
      patients (80%) with H. pylori-positive MALT lymphoma and in five (56%) of the
      nine patients with H. pylori-negative MALT lymphoma; no significant difference
      was observed between the groups (p=0.135). The other treatment modalities,
      including radiation therapy, chemotherapy, and surgery, were effective
      irrespective of H. pylori infection status, with no significant difference in the
      treatment response between H. pylori-positive and H. pylori-negative MALT
      lymphomas. CONCLUSIONS: H. pylori eradication therapy may be considered as a
      first-line treatment regardless of H. pylori infection status.

PMID- 25071907
TI  - Hypocholesterolemia in patients with an amebic liver abscess.
AB  - BACKGROUND/AIMS: Many parasites induce changes in the lipid profiles of the host.
      Cholesterol increases the virulence of Entamoeba histolytica in animal models and
      in vitro culture. This study aimed to determine, in patients with an amebic liver
      abscess, the correlation between cholesterol and other features, such as the size
      and number of abscesses, standard hematological and serum chemistry profiles,
      liver tests, and duration of hospital stay. METHODS: A total of 108 patients with
      an amebic liver abscess and 140 clinically healthy volunteers were investigated.
      Cholesterol and triglycerides were measured in the sera. The data from medical
      observations and laboratory tests were obtained from the clinical records.
      RESULTS: A total of 93% of patients with an amebic liver abscess showed
      hypocholesterolemia not related to any of the studied parameters. Liver function
      tests correlated with the size of the abscess. The most severe cases of amebic
      liver disease or death were found in patients whose cholesterol levels continued
      to decrease despite receiving antiamebic treatment and hospital care.
      CONCLUSIONS: Our results show that the hypocholesterolemia observed in patients
      with an amebic liver abscess is not related to any of the clinical and laboratory
      features analyzed. This is the first study relating hypocholesterolemia to
      severity of hepatic amebiasis.

PMID- 25071909
TI  - Regional distribution of hepatitis C virus infection in the Republic of Korea,
      2007-2011.
AB  - BACKGROUND/AIMS: In Korea, hepatitis C is included as an infectious disease in a
      sentinel surveillance system. Recently, a large variation in hepatitis C
      incidence between different regions in Korea has been noticed. The current study
      verified the nationwide distribution of hepatitis C infection for effective
      prevention and management. METHODS: We counted the number of hepatitis C patients
      who visited a hospital per county using the National Health Insurance database
      from 2007 to 2011. The age-adjusted prevalence ratio was used, and the age
      adjustment method was used as an indirect standardization method. Disease mapping
      and spatial analysis were conducted using a geographic information system.
      RESULTS: The annual prevalence of diagnosed hepatitis C was approximately 0.12%
      to 0.13% in Korea. The age-adjusted prevalence ratios in Busan, Jeonnam, and
      Gyeongnam were high (1.75, 1.4, and 1.3, respectively). The three regions in the
      southern coastal area of the Korean Peninsula were identified as a high
      prevalence cluster (Moran's index, 0.3636). CONCLUSIONS: The present study showed
      that hepatitis C infection has very large regional variation, and there are
      several high-risk areas. Preventive measures focusing on these areas should be
      applied to block the transmission of hepatitis C and reduce the disease burden.

PMID- 25071908
TI  - Prediction of a null response to pegylated interferon alpha-2b plus ribavirin in
      patients with high viral load genotype 1b hepatitis C.
AB  - BACKGROUND/AIMS: The present study aimed to clarify whether virological response
      within 2 weeks after therapy initiation can predict a null response to pegylated
      interferon alpha-2b plus ribavirin therapy in patients with high viral load
      genotype 1b hepatitis C. METHODS: The participants consisted of 72 patients with
      high viral load genotype 1b. The dynamics of viral load within 2 weeks were
      measured. RESULTS: Significant differences between null responders and nonnull
      responders were noted for interleukin (IL)-28B genotype, amino acid 70
      substitution, alpha-fetoprotein, low-density lipoprotein cholesterol, hyaluronic
      acid, and viral response. The area under the curve (AUC) for the receiver
      operating characteristic curve of the hepatitis C virus (HCV) RNA level decline
      at 2 weeks (AUC=0.993) was the highest among the factors predicting the null
      response. When the cutoff value for the HCV RNA level decline at 2 weeks was set
      at 0.80 log, the sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy in predicting a null response were 82%, 96%, 82%,
      96%, and 94%, respectively. In comparison, values for the non-TT and mutant type
      of amino acid 70 substitution were similar to those for HCV RNA level decline at
      2 weeks. CONCLUSIONS: Virological response at 2 weeks or the combination of IL
      28B and amino acid 70 substitution are accurate predictors of a null response.

PMID- 25071910
TI  - Factors affecting tumor ablation during high intensity focused ultrasound
      treatment.
AB  - BACKGROUND/AIMS: High intensity focused ultrasound (HIFU) utilizes a targeted
      extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We
      used an in vitro model to examine the effects of bone, metallic stents, plastic
      stents, metal plates, and cyst-like lesions on HIFU treatment. METHODS: HIFU was
      delivered to the phantom models implanted with foreign bodies, and the location,
      shape, and size of the ablated zones were evaluated. RESULTS: Bone and metallic
      plates reflected the ultrasound beam, shifting the ablation zone from the focal
      zone to the prefocal area. In the phantoms containing metal stent, plastic stent,
      and cyst, most of the ablative energy was reflected to the prefocal area by the
      surface, with the remainder penetrating through the phantom. The area of the
      ablated margins was significantly larger in size and volume than the intended
      focal ablation zone. CONCLUSIONS: During HIFU therapy, artificial or anatomical
      barriers could affect the direction of the ultrasound beams, shifting the
      ablation zone from the focal area to a prefocal site with a larger than expected
      ablation zone. These factors should be considered prior to HIFU treatment for
      pancreatic tumors because they could limit ablation success, in addition to
      causing complications.

PMID- 25071911
TI  - Which is the better treatment for the removal of large biliary stones? Endoscopic
      papillary large balloon dilation versus endoscopic sphincterotomy.
AB  - BACKGROUND/AIMS: We evaluated the efficacy and cost-effectiveness of endoscopic
      papillary large balloon dilation (EPLBD) for large common bile duct (CBD) stone
      removal compared with endoscopic sphincterotomy (EST). METHODS: A total of 1,580
      patients who underwent endoscopic CBD stone extraction between January 2001 and
      July 2010 were reviewed. The following inclusion criteria were applied:
      choledocholithiasis treated by EPLBD with minor EST or EST with mechanical
      lithotripsy; and follow-up >9 months after treatment. RESULTS: Forty-nine
      patients with EPLBD and 41 with EST were compared. There was no significant
      difference in the complication rates and stone recurrence rates between the two
      groups. However, significantly more endoscopic retrograde
      cholangiopancreatography (ERCP) sessions were required in the EST group to
      achieve the complete removal of stones (1.7 times vs 1.3 times; p=0.03). The mean
      cost required for complete stone removal per patient was significantly higher in
      the EST group compared to the EPLBD group (USD $1,644 vs $1,225, respectively;
      p=0.04). Dilated CBD was the only significant factor associated with recurrent
      biliary stones (relative risk, 1.09; 95% confidence interval, 1.02 to 1.17;
      p=0.02). CONCLUSIONS: EPLBD is the better treatment (compared to EST) for
      removing large CBD stones because EPLBD requires fewer ERCP sessions and is less
      expensive.

PMID- 25071912
TI  - CD64 expression is increased in patients with severe acute pancreatitis: clinical
      significance.
AB  - BACKGROUND/AIMS: Upregulated CD64 expression on neutrophils is the most useful
      marker for acute bacterial infections and systemic inflammation. However, it is
      unknown whether CD64 is involved in the pathogenesis of acute pancreatitis (AP).
      This study was designed to determine whether CD64 is implicated in severe acute
      pancreatitis (SAP), and thus, is a suitable marker for SAP. METHODS: SAP was
      induced in rats with an intraperitoneal injection of L-arginine. CD64 expression
      in the rat pancreas was determined by quantitative real-time polymerase chain
      reaction (qRT-PCR) and immunohistochemistry. Additionally, the CD64 mRNA
      expression in peripheral blood leukocytes from 21 patients with mild acute
      pancreatitis (MAP) and 10 patients with SAP was investigated at the time of
      admission and during remission by qRT-PCR. RESULTS: CD64 mRNA and protein
      expression in the pancreas was significantly higher in rats with SAP, compared to
      the controls. The CD64 expression was higher in the patients with SAP than in the
      patients with MAP. During remission, CD64 mRNA decreased in both the MAP and SAP
      patients. The area under the curve of CD64 expression for the detection of SAP
      was superior to both the Ranson and the Acute Physiology and Chronic Health
      Evaluation II scores. CONCLUSIONS: The CD64 level was significantly increased in
      correlation with the disease severity in SAP and may act as a useful marker for
      predicting the development of SAP.

PMID- 25071913
TI  - beta-Catenin activated hepatocellular adenoma: a report of three cases in Korea.
AB  - Hepatocellular adenoma (HCA) is an uncommon benign hepatic tumor, and the use of
      oral contraceptives is known to contribute to the development of HCA. Recently, a
      genotype and phenotype classification system for HCA was suggested, and malignant
      transformation to hepatocellular carcinoma (HCC) was shown to be strongly
      associated with activating mutations in beta-catenin. Here, we report three cases
      of HCA in Korean patients: 7-cm, inflammatory and beta-catenin-activated HCA with
      HCC transformation in a 46-year-old man; 13-cm, beta-catenin-activated HCA with
      cytological atypia in a 23-year-old woman; and 10-cm, pigmented, inflammatory and
      beta-catenin-activated HCA in a 36-year-old man. All cases exhibited the nuclear
      expression of beta-catenin and diffuse cytoplasmic expression of glutamine
      synthetase upon immunohistochemical staining. All tumors were completely
      resected, and the patients were followed for 3 to 6 years with no evidence of
      local recurrence or metastasis. 

PMID- 25071915
TI  - Air pollution exposure and cardiovascular disease.
AB  - Ambient air pollution (AAP) and particulate matters (PM) have been closely
      associated with adverse health effects such as respiratory disease and
      cardiovascular diseases. Previous studies have examined the adverse health
      effects associated with short- and long-term exposure to AAP and outdoor PM on
      respiratory disease. However, the effect of PM size (PM2.5 and PM10) on
      cardiovascular disease has not been well studied. Thus, it remains unclear how
      the size of the inhalable particles (coarse, fine, or ultrafine) affects
      mortality and morbidity. Airborne PM concentrations are commonly used for ambient
      air quality management worldwide, owing to the known effects on cardiorespiratory
      health. In this article, we assess the relationship between cardiovascular
      diseases and PM, with a particular focus on PM size. We discuss the association
      of PM2.5 and PM10, nitrogen dioxide (NO2), and elemental carbon with mortality
      and morbidity due to cardiovascular diseases, stroke, and altered blood pressure,
      based on epidemiological studies. In addition, we provide evidence that the
      adverse health effects of AAP and PM are more pronounced among the elderly,
      children, and people with preexisting cardiovascular and respiratory conditions.
      Finally, we critically summarize the literature pertaining to cardiovascular
      diseases, including atherosclerosis and stroke, and introduce potential studies
      to better understand the health significance of AAP and PM on cardiovascular
      disease. 

PMID- 25071914
TI  - The role of air pollutants in initiating liver disease.
AB  - Recent episodes of severe air pollution in eastern Asia have been reported in the
      scientific literature and news media. Therefore, there is growing concern about
      the systemic effects of air pollution on human health. Along with the other well
      known harmful effects of air pollution, recently, several animal models have
      provided strong evidence that air pollutants can induce liver toxicity and act to
      accelerate liver inflammation and steatosis. This review briefly describes
      examples where exposure to air pollutants was involved in liver toxicity,
      focusing on how particulate matter (PM) or carbon black (CB) may be translocated
      from lung to liver and what liver diseases are closely associated with these air
      pollutants. 

PMID- 25071916
TI  - Plant exocytic secretion of toxic compounds for defense.
AB  - In contrast to animals, plants do not have a circulatory system as well as mobile
      immune cells that allow them to protect themselves against pathogens. Instead,
      plants exclusively depend on the innate immune system to defend against
      pathogens. As typically observed in the animal innate immunity, plant immune
      responses are composed of pathogen detection, defense signaling which includes
      transcriptional reprogramming, and secretion of antimicrobial compounds. Although
      knowledge on recognition and subsequent signaling of pathogen-derived molecules
      called elicitors is now expanding, the mechanisms of how these immune molecules
      are excreted are yet poorly understood. Therefore, current understandings of how
      plants secrete defense products especially via exocytosis will be discussed in
      this review. 

PMID- 25071917
TI  - Inhalation of carbon black nanoparticles aggravates pulmonary inflammation in
      mice.
AB  - An increasing number of recent studies have focused on the impact of particulate
      matter on human health. As a model for atmospheric particulate inhalation, we
      investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice
      with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel
      aerosolization process, and the mice were exposed to the aerosol for 4 hours. We
      found that CBNP inhalation exacerbated lung inflammation, as evidenced by
      histopathology analysis and by the expression levels of interleukin-6 protein,
      fibronectin, and interferon-gamma mRNAs in lung tissues. Notably, fibronectin
      mRNA expression showed a statistically significant increase in expression after
      CBNP exposure. These data suggest that the concentration of CBNPs delivered
      (calculated to be 12.5 MUg/m(3)) can aggravate lung inflammation in mice. Our
      results also suggest that the inhalation of ultrafine particles like PM 2.5 is an
      impactful environmental risk factor for humans, particularly in susceptible
      populations with predisposing lung conditions. 

PMID- 25071918
TI  - Smoking Habits and Neuropeptides: Adiponectin, Brain-derived Neurotrophic Factor,
      and Leptin Levels.
AB  - This study aimed to identify changes in the level of neuropeptides among current
      smokers, former smokers, and individuals who had never smoked, and how smoking
      habits affect obesity and metabolic syndrome (MetS). Neuropeptide levels,
      anthropometric parameters, and metabolic syndrome diagnostic indices were
      determined among male workers; 117 of these had never smoked, whereas 58 and 198
      were former and current smokers, respectively. The total sample comprised 373
      male workers. The results obtained from anthropometric measurements showed that
      current smokers attained significantly lower body weight, body mass index, waist
      circumference, and abdominal fat thickness values than former smokers and those
      who had never smoked. Current smokers' eating habits proved worse than those of
      non-smokers and individuals who had never smoked. The level of brain-derived
      neurotrophic factor (BDNF) in the neuropeptides in the case of former smokers was
      23.6 +/- 9.2 pg/ml, higher than that of current smokers (20.4 +/- 6.1) and
      individuals who had never smoked (22.4 +/- 5.8) (F = 6.520, p = 0.002). The level
      of adiponectin among former smokers was somewhat lower than that of current
      smokers, whereas leptin levels were higher among former smokers than current
      smokers; these results were not statistically significant. A relationship was
      found between adiponectin and triglyceride among non-smokers (odds ratio = 0.660,
      beta value = -0.416, p < 0.01) and smokers (odds ratio = 0.827, beta value = 
      0.190, p < 0.05). Further, waist circumference among non-smokers (odds ratio =
      1.622, beta value = 0.483, p < 0.001) and smokers (odds ratio = 1.895, beta value
      = 0.639, p < 0.001) was associated with leptin. It was concluded that cigarette
      smoking leads to an imbalance of energy expenditure and appetite by changing the
      concentration of neuropeptides such as adiponectin, BDNF, leptin, and hsCRP, and
      influences food intake, body weight, the body mass index, blood pressure, and
      abdominal fat, which are risk factors for MetS and cardiovascular disease. 

PMID- 25071919
TI  - Evaluation of renal toxicity by combination exposure to melamine and cyanuric
      Acid in male sprague-dawley rats.
AB  - Melamine-induced nephrotoxicity is closely associated with crystal formation in
      the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA).
      However, there are few dosage-finding studies for toxicological evaluation of
      chronic co-exposure to Mel and CA. The objective of this study was to investigate
      the possible mechanism by which a Mel and CA mixture lead to renal toxicity in
      rats. Mel and CA were co-administered to rats via oral gavage for 50 days.
      Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum
      creatinine (sCr) levels. Relative kidney weights were significantly increased in
      rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr
      levels were significantly increased after Mel and CA co-exposure. Taken together,
      significant increase in KIM-1, NGAL, and calbindin levels were observed in the
      urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the
      corresponding control group. Histological analysis revealed epithelial
      degeneration and necrotic cell death in the proximal tubules of the kidney after
      co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel
      mediated renal toxicity may be influenced by CA concentrations in Mel
      contaminated milk or foods. 

PMID- 25071920
TI  - Determination of goitrogenic metabolites in the serum of male wistar rat fed
      structurally different glucosinolates.
AB  - Glucosinolates (GLSs) are abundant in cruciferous vegetables and reported to have
      anti thyroidal effects. Four GLSs (sinigrin, progoitrin, glucoerucin, and
      glucotropaeolin) were administered orally to rats, and the breakdown products of
      GLSs (GLS-BPs: thiocyanate ions, cyanide ions, organic isothiocyanates, organic
      nitriles, and organic thiocyanates) were measured in serum. Thiocyanate ions were
      measured by colorimetric method, and cyanide ions were measured with CI-GC-MS.
      Organic isothiocyanates and their metabolites were measured with the
      cyclocondensation assay. Organic nitriles and organic thiocyanates were measured
      with EI-GC-MS. In all treatment groups except for progoitrin, thiocyanate ions
      were the highest among the five GLS-BPs. In the progoitrin treated group, a high
      concentration of organic isothiocyanates (goitrin) was detected. In the
      glucoerucin treated group, a relatively low amount of goitrogenic substances was
      observed. The metabolism to thiocyanate ions happened within five hours of the
      administration, and the distribution of GLSs varied with the side chain. GLSs
      with side chains that can form stable carbocation seemed to facilitate the
      degradation reaction and produce a large amount of goitrogenic thiocyanate ions.
      Because goitrogenic metabolites can be formed without myrosinase, the
      inactivation of myrosinase during cooking would have no effect on the anti
      nutritional effect of GLSs in cruciferous vegetables. 

PMID- 25071922
TI  - Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder
      of Tenebrio molitor Larvae (Yellow Mealworm).
AB  - The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries
      and provides benefits as a new food source of protein for humans. However, no
      information exists regarding its safety for humans. The objective of the present
      study was to evaluate the genotoxicity and repeated dose oral toxicity of the
      freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated
      by a standard battery testing: bacterial reverse mutation test, in vitro
      chromosome aberration test, and in vivo micronucleus test. To assess the repeated
      dose toxicity, the powder was administered once daily by oral gavage to Sprague
      Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days.
      The parameters which were applied to the study were mortality, clinical signs,
      body and organ weights, food consumption, ophthalmology, urinalysis, hematology,
      serum chemistry, gross findings and histopathologic examination. The freezedried
      powder of T. molitor larvae was not mutagenic or clastogenic based on results of
      in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related
      changes or findings were observed in any parameters in rats after 28 days oral
      administration. In conclusion, the freeze-dried powder of T. molitor larvae was
      considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level)
      was determined to be 3000 mg/kg/day in both sexes of SD rats under our
      experimental conditions. 

PMID- 25071921
TI  - Diagnosis of trace toxic uranium ions in organic liver cell.
AB  - Uranium is toxic and radioactive traces of it can be found in natural water and
      soils. High concentrations of it in biological systems cause genetic disorders
      and diseases. For the in vivo diagnosis, micro and nano range detection limits
      are required. Here, an electrochemical assay for trace toxic uranium was searched
      using stripping voltammetry. Renewable and simplified graphite pencils electrode
      (PE) was used in a three-electrode cell system. Seawater was used instead of an
      electrolyte solution. This setup can yield good results and the detection limit
      was attained to be at 10 MUgL(-1). The developed skill can be applied to organic
      liver cell. 

PMID- 25071923
TI  - Genotoxicity Study of Polysaccharide Fraction from Astragalus membranaceus's
      Aerial Parts.
AB  - Radix Astragali, the root of Astragalus (A.) membranaceus, has been applied in a
      variety of diseases for a long time in Asian countries such as Korea and China.
      In addition, the aerial parts such as leaves and stems of A. membranaceus have
      received a great deal of attention. Recently, the polysaccharide fraction showing
      a potent immunomoduating activity was isolated from the aerial parts of A.
      membranaceus. Thus, the aerial parts of A. membranaceus would be worthy enough
      for a food material and a dietary supplement. However, they should be safe even
      though valuable. In our previous study, it was estimated that NOAEL for female
      rats are 5000 mg/kg/day of the crude polysaccharide fraction from A. membranaceus
      aboveground parts. As a series of safety evaluation, genotoxicity test for the
      crude polysaccharide fraction was carried out in this study. In conclusion, the
      three genotoxicity assays provided strong overall support that the crude
      polysaccharide fraction lacks mutagenic and/or clastogenic potential under the
      GLP-based test conditions. This indicates the aerial parts of A. membranaceus
      would be safe enough for a food material and a dietary supplement. 

PMID- 25071925
TI  - Transcriptional and functional complexity of Shank3 provides a molecular
      framework to understand the phenotypic heterogeneity of SHANK3 causing autism and
      Shank3 mutant mice.
AB  - BACKGROUND: Considerable clinical heterogeneity has been well documented amongst
      individuals with autism spectrum disorders (ASD). However, little is known about
      the biological mechanisms underlying phenotypic diversity. Genetic studies have
      established a strong causal relationship between ASD and molecular defects in the
      SHANK3 gene. Individuals with various defects of SHANK3 display considerable
      clinical heterogeneity. Different lines of Shank3 mutant mice with deletions of
      different portions of coding exons have been reported recently. Variable synaptic
      and behavioral phenotypes have been reported in these mice, which makes the
      interpretations for these data complicated without the full knowledge of the
      complexity of the Shank3 transcript structure. METHODS: We systematically
      examined alternative splicing and isoform-specific expression of Shank3 across
      different brain regions and developmental stages by regular RT-PCR, quantitative
      real time RT-PCR (q-PCR), and western blot. With these techniques, we also
      investigated the effects of neuronal activity and epigenetic modulation on
      alternative splicing and isoform-specific expression of Shank3. We explored the
      localization and influence on dendritic spine development of different Shank3
      isoforms in cultured hippocampal neurons by cellular imaging. RESULTS: The Shank3
      gene displayed an extensive array of mRNA and protein isoforms resulting from the
      combination of multiple intragenic promoters and extensive alternative splicing
      of coding exons in the mouse brain. The isoform-specific expression and
      alternative splicing of Shank3 were brain-region/cell-type specific,
      developmentally regulated, activity-dependent, and involved epigenetic
      regulation. Different subcellular distribution and differential effects on
      dendritic spine morphology were observed for different Shank3 isoforms.
      CONCLUSIONS: Our results indicate a complex transcriptional regulation of Shank3
      in mouse brains. Our analysis of select Shank3 isoforms in cultured neurons
      suggests that different Shank3 isoforms have distinct functions. Therefore, the
      different types of SHANK3 mutations found in patients with ASD and different
      exonic deletions of Shank3 in mutant mice are predicted to disrupt selective
      isoforms and result in distinct dysfunctions at the synapse with possible
      differential effects on behavior. Our comprehensive data on Shank3
      transcriptional regulation thus provides an essential molecular framework to
      understand the phenotypic diversity in SHANK3 causing ASD and Shank3 mutant mice.

PMID- 25071926
TI  - Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive
      behaviors and orbitofrontal cortex deficits.
AB  - BACKGROUND: As elegant structures designed for neural communication, synapses are
      the building bricks of our mental functions. Recently, many studies have pointed
      out that synaptic protein-associated mutations may lead to dysfunctions of social
      cognition. Dlgap2, which encodes one of the main components of scaffold proteins
      in postsynaptic density (PSD), has been addressed as a candidate gene in autism
      spectrum disorders. To elucidate the disturbance of synaptic balance arising from
      Dlgap2 loss-of-function in vivo, we thus generated Dlgap2 (-/-) mice to
      investigate their phenotypes of synaptic function and social behaviors. METHODS:
      The creation of Dlgap2 (-/-) mice was facilitated by the recombineering-based
      method, Cre-loxP system and serial backcross. Reversal learning in a water T-maze
      was used to determine repetitive behaviors. The three-chamber approach task,
      resident-intruder test and tube task were performed to characterize the social
      behaviors of mutant mice. Cortical synaptosomal fraction, Golgi-Cox staining,
      whole-cell patch electrophysiology and transmission electron microscopy were all
      applied to investigate the function and structure of synapses in the
      orbitofrontal cortex (OFC) of Dlgap2 (-/-) mice. RESULTS: Dlgap2 (-/-) mice
      displayed exacerbated aggressive behaviors in the resident-intruder task, and
      elevated social dominance in the tube test. In addition, Dlgap2 (-/-) mice
      exhibited a clear reduction of receptors and scaffold proteins in cortical
      synapses. Dlgap2 (-/-) mice also demonstrated lower spine density, decreased peak
      amplitude of miniature excitatory postsynaptic current and ultra-structural
      deficits of PSD in the OFC. CONCLUSIONS: Our findings clearly demonstrate that
      Dlgap2 plays a vital role in social behaviors and proper synaptic functions of
      the OFC. Moreover, these results may provide valuable insights into the
      neuropathology of autism.

PMID- 25071927
TI  - Neoglycosylation and neoglycorandomization: Enabling tools for the discovery of
      novel glycosylated bioactive probes and early stage leads.
AB  - This review focuses upon the development, scope, and utility of the highly
      versatile chemoselective alkoxyamine-based 'neoglycosylation' reaction first
      described by Peri and Dumy. The fundamentals of neoglycosylation and the
      subsequent development of a 'neoglycorandomization' platform to afford
      differentially-glycosylated libraries of plant-based natural products, microbial
      based natural products, and small molecule-based drugs for drug discovery
      applications are discussed.

PMID- 25071930
TI  - Efficient C-H Bond Activations via O2 Cleavage by a Dianionic Cobalt(II) Complex.
AB  - A dianionic, square planar cobalt(II) complex reacts with O2 in the presence of
      acetonitrile to give a cyanomethylcobalt(III) complex formed by C-H bond
      cleavage. Interestingly, PhIO and p-tolylazide react similarly to give the same
      cyanomethylcobalt(III) complex. Competition studies with various hydrocarbon
      substrates indicate that the rate of C-H bond cleavage greatly depends on the p
      Ka of the C-H bond, rather than on the C-H bond dissociation energy. Kinetic
      isotope experiments reveal a moderate KIE value of ca. 3.5 using either O2 or
      PhIO. The possible involvement of a cobalt(IV) oxo species in this chemistry is
      discussed.

PMID- 25071929
TI  - Selective Radical Amination of Aldehydic C(sp2)-H Bonds with Fluoroaryl Azides
      via Co(II)-Based Metalloradical Catalysis: Synthesis of N-Fluoroaryl Amides from
      Aldehydes under Neutral and Nonoxidative Conditions.
AB  - The Co(II) complex of the D2h-symmetric amidoporphyrin 3,5-Di t Bu-IbuPhyrin,
      [Co(P1)], has proven to be an effective metalloradical catalyst for
      intermolecular amination of C(sp2)-H bonds of aldehydes with fluoroaryl azides.
      The [Co(P1)]-catalyzed process can employ aldehydes as the limiting reagents and
      operate under neutral and non-oxidative conditions, generating nitrogen gas as
      the only byproduct. The metalloradical aldehydic C-H amination is suitable for
      different combinations of aldehydes and fluoroaryl azides, producing the
      corresponding N-fluoroaryl amides in good to excellent yields. A series of
      mechanistic studies support a stepwise radical mechanism for the Co(II)-catalyzed
      intermolecular C-H amination.

PMID- 25071928
TI  - New trends in aminoglycosides use.
AB  - Despite their inherent toxicity and the acquired bacterial resistance that
      continuously threaten their long-term clinical use, aminoglycosides (AGs) still
      remain valuable components of the antibiotic armamentarium. Recent literature
      shows that the AGs' role has been further expanded as multi-tasking players in
      different areas of study. This review aims at presenting some of the new trends
      observed in the use of AGs in the past decade, along with the current
      understanding of their mechanisms of action in various bacterial and eukaryotic
      cellular processes.

PMID- 25071931
TI  - Folding Thermodynamics of Protein-Like Oligomers with Heterogeneous Backbones.
AB  - The thermodynamics of protein folding are dictated by a complex interplay of
      interatomic interactions and physical forces. A variety of unnatural protein-like
      oligomers have the capacity to manifest defined folding patterns. While the
      energetics of folding in natural proteins is well studied, little is known about
      the forces that govern folding in modified backbones. Here, we explore the
      thermodynamic consequences of backbone alteration on protein folding, focusing on
      two types of chemical changes made in different structural contexts of a compact
      tertiary fold. Our results reveal a surprising favorable impact on folding
      entropy that accompanies modifications that increase disorder in the ensemble of
      unfolded states, due to differences in the solvation of natural and unnatural
      backbones.

PMID- 25071934
TI  - Enzyme-instructed self-assembly of hydrogelators consisting of nucleobases, amino
      acids, and saccharide.
AB  - We report the first example of the use of enzymes to trigger the self-assembly of
      the conjugates of nucleobases, amino acids, and saccharide to form supramolecular
      hydrogels in water, which illustrates a facile approach for the development of a
      new class of multifunctional soft materials for biomedical applications.

PMID- 25071932
TI  - In vitro pre-vascularisation of tissue-engineered constructs A co-culture
      perspective.
AB  - In vitro pre-vascularization is one of the main vascularization strategies in the
      tissue engineering field. Culturing cells within a tissue-engineered construct
      (TEC) prior to implantation provides researchers with a greater degree of control
      over the fate of the cells. However, balancing the diverse range of different
      cell culture parameters in vitro is seldom easy and in most cases, especially in
      highly vascularized tissues, more than one cell type will reside within the cell
      culture system. Culturing multiple cell types in the same construct presents its
      own unique challenges and pitfalls. The following review examines endothelial
      driven vascularization and evaluates the direct and indirect role other cell
      types have in vessel and capillary formation. The article then analyses the
      different parameters researchers can modulate in a co-culture system in order to
      design optimal tissue-engineered constructs to match desired clinical
      applications. 

PMID- 25071935
TI  - The microbiome in pediatric cystic fibrosis patients: the role of shared
      environment suggests a window of intervention.
AB  - BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the CFTR gene that
      predispose the airway to infection. Chronic infection by pathogens such as
      Pseudomonas aeruginosa leads to inflammation that gradually degrades lung
      function, resulting in morbidity and early mortality. In a previous study of CF
      monozygotic twins, we demonstrate that genetic modifiers significantly affect the
      establishment of persistent P. aeruginosa colonization in CF. Recognizing that
      bacteria other than P. aeruginosa contribute to the CF microbiome and associated
      pathology, we used deep sequencing of sputum from pediatric monozygotic twins and
      nontwin siblings with CF to characterize pediatric bacterial communities and the
      role that genetics plays in their evolution. FINDINGS: We found that the
      microbial communities in sputum from pediatric patients living together were much
      more alike than those from pediatric individuals living apart, regardless of
      whether samples were taken from monozygous twins or from nontwin CF siblings
      living together, which we used as a proxy for dizygous twins. In contrast, adult
      communities were comparatively monolithic and much less diverse than the
      microbiome of pediatric patients. CONCLUSION: Taken together, these data and
      other recent studies suggest that as patients age, the CF microbiome becomes less
      diverse, more refractory to treatment and dominated by mucoid P. aeruginosa, as
      well as being associated with accelerated pulmonary decline. Our studies show
      that the microbiome of pediatric patients is susceptible to environmental
      influences, suggesting that interventions to preserve the community structure
      found in young CF patients might be possible, perhaps slowing disease
      progression.

PMID- 25071936
TI  - Fusiform superior cerebellar artery aneurysm treated with STA-SCA bypass and
      trapping.
AB  - BACKGROUND: Fusiform aneurysms of cerebellar arteries are rare. Different
      surgical techniques to address these challenging lesions have been described, and
      their application depends on whether the goal is to maintain the flow in the
      parent vessel or to occlude it. CASE DESCRIPTION: The authors reported a case of
      a fusiform aneurysm located in the lateral pontomesencephalic segment of the
      superior cerebellar artery (SCA) in a 32-year-old man who presented with
      subarachnoid hemorrhage. The patient was subjected to aneurysm trapping followed
      by a bypass between the superficial temporal artery (STA) and SCA and had an
      uneventful recovery. CONCLUSIONS: Although only a few cases of fusiform aneurysms
      in the supracerebellar artery have been reported in the literature, the treatment
      strategies adopted were diverse. In selected cases of patients in good
      neurological condition with ruptured fusiform aneurysms at the proximal segments
      of SCA and who have poor evidence of collateral supply, the possibility of a STA
      SCA bypass with aneurysm trapping must be considered. A review of the current
      treatment modalities of this pathology is also presented.

PMID- 25071933
TI  - Zn(II)-coordination modulated ligand photophysical processes - the development of
      fluorescent indicators for imaging biological Zn(II) ions.
AB  - Molecular photophysics and metal coordination chemistry are the two fundamental
      pillars that support the development of fluorescent cation indicators. In this
      article, we describe how Zn(II)-coordination alters various ligand-centered
      photophysical processes that are pertinent to developing Zn(II) indicators. The
      main aim is to show how small organic Zn(II) indicators work under the
      constraints of specific requirements, including Zn(II) detection range,
      photophysical requirements such as excitation energy and emission color, temporal
      and spatial resolutions in a heterogeneous intracellular environment, and
      fluorescence response selectivity between similar cations such as Zn(II) and
      Cd(II). In the last section, the biological questions that fluorescent Zn(II)
      indicators help to answer are described, which have been motivating and
      challenging this field of research.

PMID- 25071937
TI  - Giant vertebral artery aneurysm in a child treated with endovascular parent
      artery occlusion and coil embolization.
AB  - BACKGROUND: Intracranial giant vertebral artery aneurysms are extremely rare in
      the pediatric population and are associated with significant morbidity and
      mortality. The present report describes a case of a pediatric patient with giant
      vertebral artery aneurysm who presented with intracranial mass effect. This
      patient was successfully treated with endovascular parent artery occlusion and
      coil embolization. CASE DESCRIPTION: A 7-year-old girl presented with
      tetraparesis, ataxia, dysphagia, and dysphonia. Cerebral angiography revealed
      intracranial giant aneurysm arising from the right vertebral artery. The patient
      underwent endovascular parent artery occlusion alone to facilitate aneurysmal
      thrombosis as an initial treatment. This was done to avoid a coil mass effect to
      the brainstem. However, incomplete thrombosis occurred in the vicinity of the
      vertebral artery union. Therefore, additional coil embolization for residual
      aneurysm was performed. Two additional coil embolization procedures were
      performed in response to recurrence. Mass effect and clinical symptoms gradually
      improved, and the patient had no associated morbidity or recurrence at 2 years
      after the last fourth coil embolization. CONCLUSION: Intracranial giant vertebral
      artery aneurysms are rare and challenging in pediatric patients. Staged
      endovascular strategy can be a safe and effective treatment option.

PMID- 25071938
TI  - Co-occurrence of a cerebral cavernous malformation and an orbital cavernous
      hemangioma in a patient with seizures and visual symptoms: Rare crossroads for
      vascular malformations.
AB  - BACKGROUND: Cerebral cavernous malformations (CCMs) are angiographically occult
      vascular malformations of the central nervous system. As a result of hemorrhage
      and mass effect, patients may present with focal neurologic deficits, seizures,
      and other symptoms necessitating treatment. Once symptomatic, most often from
      hemorrhage, CCMs are treated with microsurgical resection. Orbital cavernous
      hemangiomas (OCHs) are similar but distinct vascular malformations that present
      within the orbital cavity. Even though CCMs and OCHs are both marked by dilated
      endothelial-lined vascular channels, they are infrequently seen in the same
      patient. CASE DESCRIPTION: We provide a brief overview of the two related
      pathologies in the context of a patient presenting to our care with concomitant
      lesions, which were both resected in full without complication. CONCLUSION: This
      is the first known report that describes a case of concomitant CCM and OCH and
      explores the origins of two pathologies that are rarely encountered together in
      neurosurgical practice. Recognition of disparate symptomatologies is important
      for properly managing these patients.

PMID- 25071939
TI  - Resolution of bilateral moyamoya associated collateral vessel aneurysms:
      Rationale for endovascular versus surgical intervention.
AB  - BACKGROUND: Management of aneurysms associated with deep collateral vessels in
      moyamoya disease is challenging both from an endovascular and a surgical
      standpoint. Difficulties with access or localization, and compromise of the
      collateral circulation with subsequent ischemia are the primary concerns, making
      direct obliteration potentially unfeasible or risky. Alternatively, superficial
      temporal artery-middle cerebral artery bypass is another potential strategy for
      resolution of these aneurysms. CASE DESCRIPTION: Presented are the findings and
      management for a patient with moyamoya disease and bilateral deep collateral
      vessel aneurysms, successfully treated with endovascular obliteration following a
      right-sided hemorrhage and subsequently with bypass for an unruptured but growing
      contralateral aneurysm. CONCLUSIONS: A rationale and approach to management is
      outlined, as derived from review of the current literature and the illustrative
      case with bilateral collateral vessel aneurysms.

PMID- 25071940
TI  - Life-threatening allergic vasculitis after clipping an unruptured aneurysm: Case
      report, weighing the risk of nickel allergy.
AB  - BACKGROUND: This case report represents one of the estimated 17,000 aneurysms
      clipped annually in the United States, often with nickel-containing clips. The
      authors highlight the development of life-threatening allergic vasculitis in a 33
      year-old woman after aneurysm clipping. CASE DESCRIPTION: After suffering
      subarachnoid hemorrhage, the patient had coil embolization at another facility
      for rupture of a right internal carotid artery (ICA) aneurysm. An incidental
      finding, an unruptured left posterior communicating artery aneurysm unamenable to
      coiling, was then successfully clipped via a left pterional craniotomy. Arriving
      in our emergency department 11 days later, she progressively declined during the
      next weeks, facing deteriorating clinical status (i.e. seizures) and additional
      infarctions in the left frontal lobe, midline shift, and new infarctions in the
      bilateral frontal lobe, right sylvian, right insular regions, and posterior
      cerebral artery distribution. During decompressive surgery, biopsy findings
      raised the possibility of lymphocytic vasculitis; consultations with
      rheumatology, allergy, and immunology specialists identified that our patient had
      a nickel allergy. After reoperation to replace the nickel-containing clip with
      one of a titanium alloy, the patient had an uncomplicated postoperative course
      and was discharged 6 days later to a rehabilitation facility. CONCLUSIONS: Nickel
      related allergies are more common than appreciated, affecting up to 10% of
      patients. Fortunately, severe reactions are rare; nevertheless, vascular
      neurosurgeons should be aware of this potential complication when using cobalt
      alloy aneurysms clips. The use of titanium alloy clips eliminates this risk.

PMID- 25071941
TI  - A treatment-refractory spinal dural arteriovenous fistula sharing arterial origin
      with the Artery of Adamkiewicz: Repeated endovascular treatment after failed
      microsurgery.
AB  - BACKGROUND: Effective management of a spinal dural arteriovenous fistula (SDAVF)
      can be accomplished with either microsurgery or endovascular embolization, but
      there is a consensus that in patients in whom a radiculomedullary artery
      supplying the anterior spinal artery (ASA) originates from the same feeding
      artery as the SDAVF, the endovascular approach is to be avoided. CASE
      DESCRIPTION: The patient was a 46-year-old woman with progressive lower limb
      paraparesis, sensory deficit, and sphincter dysfunction. Magnetic resonance
      imaging (MRI) and spinal angiography showed an SDAVF fed by a branch from the
      left second lumbar segmental artery, and the artery of Adamkiewicz (AA), a major
      ASA supplier, originating from the same segmental artery just proximal to the
      SDAVF. Microsurgical disconnection of the SDAVF was attempted, but failed.
      Embolization with cyanoacrylates was done in two occasions, the first time
      through a microcatheter placed just distal to the origin of the AA and the second
      time through another feeder coming from the same segmental artery that could not
      be visualized in the previous angiographies. All procedures were neurologically
      uncomplicated. Magnetic resonance imaging (MRI) 1 month after the last
      embolization showed resolution of the spinal cord edema. MRI scan taken 68 months
      after embolization revealed a slightly atrophic spinal cord with visible central
      canal and no recurrence of medullary edema. The patient presented good, but
      incomplete neurological improvement. CONCLUSION: Microsurgery is the first choice
      for an SDAVF branching off the same radiculomedullary artery supplying the ASA,
      but uncomplicated embolization can be feasible after failed surgery.

PMID- 25071942
TI  - Dyspnea and choking as presenting symptoms in primary medulla oblongata
      germinoma.
AB  - BACKGROUND: The medulla oblongata is the lower half of the brainstem. It contains
      the cardiac, respiratory, vomiting, and vasomotor centers and deals with
      autonomic functions such as breathing, heartbeat, and blood pressure. Primary
      medulla oblongata germinoma is very rare and less than 20 cases have been
      reported in the English literature. CASE DESCRIPTION: A 22-year-old female
      without any particular past medical history presented to us in October 2012 with
      the chief complaint of dyspnea and frequent choking for 1 month. Neurological
      examination revealed lower cranial nerve palsies and nystagmus. Her brain
      computed tomography (CT) and brain magnetic resonance imaging (MRI) demonstrated
      a mass lesion at the dorsal surface of medulla oblongata with extension into the
      inferior fourth ventricle and foramen magnum. She underwent bilateral
      suboccipital craniotomy and C1 laminoplasty with the grossly total resection of
      the tumor. The histological examination of the tumor proved germinoma.
      Postoperative adjuvant radiotherapy was arranged. The latest brain MRI and whole
      spine MRI done 1 year after surgery showed neither residual nor recurrent tumor
      in the whole axis. She is regularly followed-up at our outpatient department and
      is doing well except having left vocal cord palsy, which occurred before surgery.
      CONCLUSION: Medulloblastoma, ependymoma, glioma, hemangioblastoma, and cavernous
      angioma are common intraaxial tumors in the medulla oblongata and fourth
      ventricle. Intracranial germ cell tumors originate from extragonadal seminal
      cells and have been found in 0.4-3.4% of patients with primary central nervous
      system (CNS) tumors in Western countries, while the incidence is reported to be 5
      8 times greater in Japan and the Far East. Although germinoma of medulla
      oblongata is rare and difficult to diagnose preoperatively, it should be included
      in the differential diagnosis of medulla masses with fourth ventricle extension,
      especially in Asian population.

PMID- 25071943
TI  - Noncontact quantitative biomechanical characterization of cardiac muscle using
      shear wave imaging optical coherence tomography.
AB  - We report on a quantitative optical elastographic method based on shear wave
      imaging optical coherence tomography (SWI-OCT) for biomechanical characterization
      of cardiac muscle through noncontact elasticity measurement. The SWI-OCT system
      employs a focused air-puff device for localized loading of the cardiac muscle and
      utilizes phase-sensitive OCT to monitor the induced tissue deformation. Phase
      information from the optical interferometry is used to reconstruct 2-D depth
      resolved shear wave propagation inside the muscle tissue. Cross-correlation of
      the displacement profiles at various spatial locations in the propagation
      direction is applied to measure the group velocity of the shear waves, based on
      which the Young's modulus of tissue is quantified. The quantitative feature and
      measurement accuracy of this method is demonstrated from the experiments on
      tissue-mimicking phantoms with the verification using uniaxial compression test.
      The experiments are performed on ex vivo cardiac muscle tissue from mice with
      normal and genetically altered myocardium. Our results indicate this optical
      elastographic technique is useful as a noncontact tool to assist the cardiac
      muscle studies. 

PMID- 25071944
TI  - Artificially-induced organelles are optimal targets for optical trapping
      experiments in living cells.
AB  - Optical trapping supplies information on the structural, kinetic or rheological
      properties of inner constituents of the cell. However, the application of
      significant forces to intracellular objects is notoriously difficult due to a
      combination of factors, such as the small difference between the refractive
      indices of the target structures and the cytoplasm. Here we discuss the
      possibility of artificially inducing the formation of spherical organelles in the
      endoplasmic reticulum, which would contain densely packed engineered proteins, to
      be used as optimized targets for optical trapping experiments. The high index of
      refraction and large size of our organelles provide a firm grip for optical
      trapping and thereby allow us to exert large forces easily within safe
      irradiation limits. This has clear advantages over alternative probes, such as
      subcellular organelles or internalized synthetic beads. 

PMID- 25071945
TI  - Investigation of temporal vascular effects induced by focused ultrasound
      treatment with speckle-variance optical coherence tomography.
AB  - Focused ultrasound (FUS) can be used to locally and temporally enhance vascular
      permeability, improving the efficiency of drug delivery from the blood vessels
      into the surrounding tissue. However, it is difficult to evaluate in real time
      the effect induced by FUS and to noninvasively observe the permeability
      enhancement. In this study, speckle-variance optical coherence tomography (SVOCT)
      was implemented for the investigation of temporal effects on vessels induced by
      FUS treatment. With OCT scanning, the dynamic change in vessels during FUS
      exposure can be observed and studied. Moreover, the vascular effects induced by
      FUS treatment with and without the presence of microbubbles were investigated and
      quantitatively compared. Additionally, 2D and 3D speckle-variance images were
      used for quantitative observation of blood leakage from vessels due to the
      permeability enhancement caused by FUS, which could be an indicator that can be
      used to determine the influence of FUS power exposure. In conclusion, SVOCT can
      be a useful tool for monitoring FUS treatment in real time, facilitating the
      dynamic observation of temporal effects and helping to determine the optimal FUS
      power. 

PMID- 25071946
TI  - A 5-mm piezo-scanning fiber device for high speed ultrafast laser microsurgery.
AB  - Towards developing precise microsurgery tools for the clinic, we previously
      developed image-guided miniaturized devices using low repetition rate amplified
      ultrafast lasers for surgery. To improve the speed of tissue removal while
      reducing device diameter, here we present a new 5-mm diameter device that
      delivers high-repetition rate laser pulses for high speed ultrafast laser
      microsurgery. The device consists of an air-core photonic bandgap fiber (PBF) for
      the delivery of high energy pulses, a piezoelectric tube actuator for fiber
      scanning, and two aspheric lenses for focusing the light. Its inline optical
      architecture provides easy alignment and substantial size reduction to 5 mm
      diameter as compared to our previous MEMS-scanning devices while realizing
      improved intensity squared (two-photon) lateral and axial resolutions of 1.16 MUm
      and 11.46 MUm, respectively. Our study also sheds light on the maximum pulse
      energies that can be delivered through the air-core PBF and identifies cladding
      damage at the input facet of the fiber as the limiting factor. We have achieved a
      maximum energy delivery larger than 700 nJ at 92% coupling efficiency. An in
      depth analysis reveals how this value is greatly affected by possible slight
      misalignments of the beam during coupling and the measured small beam pointing
      fluctuations. In the absence of these imperfections, self-phase modulation
      becomes the limiting factor for the maximum energy delivery, setting the
      theoretical upper bound to near 2 MUJ for a 1-m long, 7-MUm, air-core PBF.
      Finally, the use of a 300 kHz repetition rate fiber laser enabled rapid ablation
      of 150 um x 150 um area within only 50 ms. Such ablation speeds can now allow the
      surgeons to translate the surgery device as fast as ~4 mm/s to continuously
      remove a thin layer of a 150 um wide tissue. Thanks to a high optical
      transmission efficiency of the in-line optical architecture of the device and
      improved resolution, we could successfully perform ablation of scarred cheek
      pouch tissue, drilling through a thin slice. With further development, this
      device can serve as a precise and high speed ultrafast laser scalpel in the
      clinic. 

PMID- 25071947
TI  - Determination of reference values for optical properties of liquid phantoms based
      on Intralipid and India ink.
AB  - A multi-center study has been set up to accurately characterize the optical
      properties of diffusive liquid phantoms based on Intralipid and India ink at near
      infrared (NIR) wavelengths. Nine research laboratories from six countries
      adopting different measurement techniques, instrumental set-ups, and data
      analysis methods determined at their best the optical properties and relative
      uncertainties of diffusive dilutions prepared with common samples of the two
      compounds. By exploiting a suitable statistical model, comprehensive reference
      values at three NIR wavelengths for the intrinsic absorption coefficient of India
      ink and the intrinsic reduced scattering coefficient of Intralipid-20% were
      determined with an uncertainty of about 2% or better, depending on the wavelength
      considered, and 1%, respectively. Even if in this study we focused on particular
      batches of India ink and Intralipid, the reference values determined here
      represent a solid and useful starting point for preparing diffusive liquid
      phantoms with accurately defined optical properties. Furthermore, due to the
      ready availability, low cost, long-term stability and batch-to-batch
      reproducibility of these compounds, they provide a unique fundamental tool for
      the calibration and performance assessment of diffuse optical spectroscopy
      instrumentation intended to be used in laboratory or clinical environment.
      Finally, the collaborative work presented here demonstrates that the accuracy
      level attained in this work for optical properties of diffusive phantoms is
      reliable. 

PMID- 25071949
TI  - Variations in optical coherence tomography resolution and uniformity: a multi
      system performance comparison.
AB  - Point spread function (PSF) phantoms based on unstructured distributions of sub
      resolution particles in a transparent matrix have been demonstrated as a useful
      tool for evaluating resolution and its spatial variation across image volumes in
      optical coherence tomography (OCT) systems. Measurements based on PSF phantoms
      have the potential to become a standard test method for consistent, objective and
      quantitative inter-comparison of OCT system performance. Towards this end, we
      have evaluated three PSF phantoms and investigated their ability to compare the
      performance of four OCT systems. The phantoms are based on 260-nm-diameter gold
      nanoshells, 400-nm-diameter iron oxide particles and 1.5-micron-diameter silica
      particles. The OCT systems included spectral-domain and swept source systems in
      free-beam geometries as well as a time-domain system in both free-beam and
      fiberoptic probe geometries. Results indicated that iron oxide particles and gold
      nanoshells were most effective for measuring spatial variations in the magnitude
      and shape of PSFs across the image volume. The intensity of individual particles
      was also used to evaluate spatial variations in signal intensity uniformity.
      Significant system-to-system differences in resolution and signal intensity and
      their spatial variation were readily quantified. The phantoms proved useful for
      identification and characterization of irregularities such as astigmatism. Our
      multi-system results provide evidence of the practical utility of PSF-phantom
      based test methods for quantitative inter-comparison of OCT system resolution and
      signal uniformity. 

PMID- 25071948
TI  - Temperature-sensitive gating of hCx26: high-resolution Raman spectroscopy sheds
      light on conformational changes.
AB  - The temperature-sensitive gating of human Connexin 26 (hCx26) was analyzed with
      confocal Raman microscopy. High-resolution Raman spectra covering the spectral
      range between 400 and 1500 rel. cm(-1) with a spectral resolution of 1 cm(-1)
      were fully annotated, revealing notable differences between the spectrum recorded
      from solubilized hCx26 in Ca(2+)-buffered POPC at 10 degrees C and any other set
      of protein conditions (temperature, Ca(2+) presence, POPC presence). Spectral
      components originating from specific amino acids show that the TM1/EL1 parahelix
      and probably the TM4 trans-membrane helix and the plug domain are involved in the
      gating process responsible for fully closing the hemichannel. 

PMID- 25071950
TI  - Biomolecule-to-fluorescent-color encoder: modulation of fluorescence emission via
      DNA structural changes.
AB  - A biomolecule-to-fluorescent-color (B/F) encoder for optical readout of
      biomolecular information is proposed. In the B/F encoder, a set of fluorescence
      wavelengths and their intensity levels are used for coding of a biomolecular
      signal. A hybridization chain reaction of hairpin DNAs labeled with fluorescent
      reporters was performed to generate the fluorescence color codes. The
      fluorescence is modulated via fluorescence resonance energy transfer, which is
      controlled by DNA structural changes. The results demonstrate that fluorescent
      color codes can be configured based on two wavelengths and five intensities using
      the B/F encoder, and the assigned codes can be retrieved via fluorescence
      measurements. 

PMID- 25071951
TI  - Probability method for Cerenkov luminescence tomography based on conformance
      error minimization.
AB  - Cerenkov luminescence tomography (CLT) was developed to reconstruct a three
      dimensional (3D) distribution of radioactive probes inside a living animal.
      Reconstruction methods are generally performed within a unique framework by
      searching for the optimum solution. However, the ill-posed aspect of the inverse
      problem usually results in the reconstruction being non-robust. In addition, the
      reconstructed result may not match reality since the difference between the
      highest and lowest uptakes of the resulting radiotracers may be considerably
      large, therefore the biological significance is lost. In this paper, based on the
      minimization of a conformance error, a probability method is proposed that
      consists of qualitative and quantitative modules. The proposed method first
      pinpoints the organ that contains the light source. Next, we developed a 0-1
      linear optimization subject to a space constraint to model the CLT inverse
      problem, which was transformed into a forward problem by employing a region
      growing method to solve the optimization. After running through all of the
      elements used to grow the sources, a source sequence was obtained. Finally, the
      probability of each discrete node being the light source inside the organ was
      reconstructed. One numerical study and two in vivo experiments were conducted to
      verify the performance of the proposed algorithm, and comparisons were carried
      out using the hp-finite element method (hp-FEM). The results suggested that our
      proposed probability method was more robust and reasonable than hp-FEM. 

PMID- 25071952
TI  - Optical coherence micro-elastography: mechanical-contrast imaging of tissue
      microstructure.
AB  - We present optical coherence micro-elastography, an improved form of compression
      optical coherence elastography. We demonstrate the capacity of this technique to
      produce en face images, closely corresponding with histology, that reveal micro
      scale mechanical contrast in human breast and lymph node tissues. We use phase
      sensitive, three-dimensional optical coherence tomography (OCT) to probe the
      nanometer-to-micrometer-scale axial displacements in tissues induced by
      compressive loading. Optical coherence micro-elastography incorporates common
      path interferometry, weighted averaging of the complex OCT signal and weighted
      least-squares regression. Using three-dimensional phase unwrapping, we have
      increased the maximum detectable strain eleven-fold over no unwrapping and the
      minimum detectable strain is 2.6 MUepsilon. We demonstrate the potential of
      mechanical over optical contrast for visualizing micro-scale tissue structures in
      human breast cancer pathology and lymph node morphology. 

PMID- 25071953
TI  - Vibrationally resonant sum-frequency generation microscopy with a solid immersion
      lens.
AB  - We use a hemispheric sapphire lens in combination with an off-axis parabolic
      mirror to demonstrate high-resolution vibrationally resonant sum-frequency
      generation (VR-SFG) microscopy in the mid-infrared range. With the sapphire lens
      as an immersed solid medium, the numerical aperture (NA) of the parabolic mirror
      objective is enhanced by a factor of 1.72, from 0.42 to 0.72, close to the
      theoretical value of 1.76 ( = nsapphire). The measured lateral resolution is as
      high as 0.64 MUm. We show the practical utility of the sapphire immersion lens by
      imaging collagen-rich tissues with and without the solid immersion lens. 

PMID- 25071954
TI  - Integrated photoacoustic, ultrasound and fluorescence platform for diagnostic
      medical imaging-proof of concept study with a tissue mimicking phantom.
AB  - The structural and molecular heterogeneities of biological tissues demand the
      interrogation of the samples with multiple energy sources and provide
      visualization capabilities at varying spatial resolution and depth scales for
      obtaining complementary diagnostic information. A novel multi-modal imaging
      approach that uses optical and acoustic energies to perform photoacoustic,
      ultrasound and fluorescence imaging at multiple resolution scales from the tissue
      surface and depth is proposed in this paper. The system comprises of two distinct
      forms of hardware level integration so as to have an integrated imaging system
      under a single instrumentation set-up. The experimental studies show that the
      system is capable of mapping high resolution fluorescence signatures from the
      surface, optical absorption and acoustic heterogeneities along the depth (>2cm)
      of the tissue at multi-scale resolution (<1um to <0.5mm). 

PMID- 25071955
TI  - Dynamic light scattering from pulsatile flow in the presence of induced motion
      artifacts.
AB  - Continuous health monitoring has become a major theme of our aging society.
      Portable devices play an important role here. Many optical portable devices are
      susceptible to motion induced artifacts. We have performed an experimental study
      for detection of fluid pulsation based on multi-exposure speckle images, in
      presence of motion induced artifacts. Induced motion of a wide range of
      frequencies and amplitudes were generated to resemble sensor motion with respect
      to skin. The data was analyzed using speckle contrast and correlation. We
      concluded that both techniques have their own advantages, depending on the
      measurement configuration. A study of angles between illumination and detection
      revealed that larger angles yields better signal. Shorter exposure time was more
      successful in extracting the signal. We also performed in-vivo measurements that
      agree with the in-vitro case. We also show that a minimum collection of two
      pixels from the speckle image is sufficient to extract relevant results. 

PMID- 25071956
TI  - Optimization of camera exposure durations for multi-exposure speckle imaging of
      the microcirculation.
AB  - Improved Laser Speckle Contrast Imaging (LSCI) blood flow analyses that
      incorporate inverse models of the underlying laser-tissue interaction have been
      used to develop more quantitative implementations of speckle flowmetry such as
      Multi-Exposure Speckle Imaging (MESI). In this paper, we determine the optimal
      camera exposure durations required for obtaining flow information with comparable
      accuracy with the prevailing MESI implementation utilized in recent in vivo
      rodent studies. A looping leave-one-out (LOO) algorithm was used to identify
      exposure subsets which were analyzed for accuracy against flows obtained from
      analysis with the original full exposure set over 9 animals comprising n = 314
      regional flow measurements. From the 15 original exposures, 6 exposures were
      found using the LOO process to provide comparable accuracy, defined as being no
      more than 10% deviant, with the original flow measurements. The optimal subset of
      exposures provides a basis set of camera durations for speckle flowmetry studies
      of the microcirculation and confers a two-fold faster acquisition rate and a 28%
      reduction in processing time without sacrificing accuracy. Additionally, the
      optimization process can be used to identify further reductions in the exposure
      subsets for tailoring imaging over less expansive flow distributions to enable
      even faster imaging. 

PMID- 25071957
TI  - A quantitative method for measurement of HL-60 cell apoptosis based on
      diffraction imaging flow cytometry technique.
AB  - A quantitative method for measurement of apoptosis in HL-60 cells based on
      polarization diffraction imaging flow cytometry technique is presented in this
      paper. Through comparative study with existing methods and the analysis of
      diffraction images by a gray level co-occurrence matrix algorithm (GLCM), we
      found 4 GLCM parameters of contrast (CON), cluster shade (CLS), correlation (COR)
      and dissimilarity (DIS) exhibit high sensitivities as the apoptotic rates. It was
      further demonstrated that the CLS parameter correlates significantly (R(2) =
      0.899) with the degree of nuclear fragmentation and other three parameters showed
      a very good correlations (R(2) ranges from 0.69 to 0.90). These results
      demonstrated that the new method has the capability for rapid and accurate
      extraction of morphological features to quantify cellular apoptosis without the
      need for cell staining. 

PMID- 25071958
TI  - Exploring diazepam's effect on hemodynamic responses of mouse brain tissue by
      optical spectroscopic imaging.
AB  - In this study, a simple duel-optical spectroscopic imaging apparatus capable of
      simultaneously determining relative changes in brain oxy-and deoxy-hemoglobin
      concentrations was used following administration of the anxiolytic compound
      diazepam in mice with strong dominant (Dom) and submissive (Sub) behavioral
      traits. Three month old mice (n = 30) were anesthetized and after 10 min of
      baseline imaging, diazepam (1.5 mg/kg) was administered and measurements were
      taken for 80 min. The mouse head was illuminated by white light based LED's and
      diffused reflected light passing through different channels, consisting of a
      bandpass filter and a CCD camera, respectively, was collected and analyzed to
      measure the hemodynamic response. This work's major findings are threefold:
      first, Dom and Sub animals showed statistically significant differences in
      hemodynamic response to diazepam administration. Secondly, diazepam was found to
      more strongly affect the Sub group. Thirdly, different time-series profiles were
      observed post-injection, which can serve as a possible marker for the groups'
      differentiation. To the best of our knowledge, this is the first report on the
      effects of an anxiolytic drug on brain hemodynamic responses in mice using
      diffused light optical imaging. 

PMID- 25071959
TI  - Analysis of macular OCT images using deformable registration.
AB  - Optical coherence tomography (OCT) of the macula has become increasingly
      important in the investigation of retinal pathology. However, deformable image
      registration, which is used for aligning subjects for pairwise comparisons,
      population averaging, and atlas label transfer, has not been well-developed and
      demonstrated on OCT images. In this paper, we present a deformable image
      registration approach designed specifically for macular OCT images. The approach
      begins with an initial translation to align the fovea of each subject, followed
      by a linear rescaling to align the top and bottom retinal boundaries. Finally,
      the layers within the retina are aligned by a deformable registration using one
      dimensional radial basis functions. The algorithm was validated using manual
      delineations of retinal layers in OCT images from a cohort consisting of healthy
      controls and patients diagnosed with multiple sclerosis (MS). We show that the
      algorithm overcomes the shortcomings of existing generic registration methods,
      which cannot be readily applied to OCT images. A successful deformable image
      registration algorithm for macular OCT opens up a variety of population based
      analysis techniques that are regularly used in other imaging modalities, such as
      spatial normalization, statistical atlas creation, and voxel based morphometry.
      Examples of these applications are provided to demonstrate the potential benefits
      such techniques can have on our understanding of retinal disease. In particular,
      included is a pilot study of localized volumetric changes between healthy
      controls and MS patients using the proposed registration algorithm. 

PMID- 25071960
TI  - Detecting abnormality in optic nerve head images using a feature extraction
      analysis.
AB  - Imaging and evaluation of the optic nerve head (ONH) plays an essential part in
      the detection and clinical management of glaucoma. The morphological
      characteristics of ONHs vary greatly from person to person and this variability
      means it is difficult to quantify them in a standardized way. We developed and
      evaluated a feature extraction approach using shift-invariant wavelet packet and
      kernel principal component analysis to quantify the shape features in ONH images
      acquired by scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT]).
      The methods were developed and tested on 1996 eyes from three different clinical
      centers. A shape abnormality score (SAS) was developed from extracted features
      using a Gaussian process to identify glaucomatous abnormality. SAS can be used as
      a diagnostic index to quantify the overall likelihood of ONH abnormality. Maps
      showing areas of likely abnormality within the ONH were also derived. Diagnostic
      performance of the technique, as estimated by ROC analysis, was significantly
      better than the classification tools currently used in the HRT software - the
      technique offers the additional advantage of working with all images and is fully
      automated. 

PMID- 25071961
TI  - Molecular orientation sensitive second harmonic microscopy by radially and
      azimuthally polarized light.
AB  - We demonstrate the possibility to switch the z-polarization component of the
      illumination in the vicinity of the focus of high-NA objective lenses by applying
      radially and azimuthally polarized incident light. The influence of the field
      distribution on nonlinear effects was first investigated by the means of
      simulations. These were performed for high-NA objective lenses commonly used in
      nonlinear microscopy. Special attention is paid to the influence of the
      polarization of the incoming field. For linearly, circularly and radially
      polarized light a considerable polarization component in z-direction is generated
      by high NA focusing. Azimuthal polarization is an exceptional case: even for
      strong focusing no z-component arises. Furthermore, the influence of the input
      polarization on the intensity contributing to the nonlinear signal generation was
      computed. No distinct difference between comparable input polarization states was
      found for chosen thresholds of nonlinear signal generation. Differences in signal
      generation for radially and azimuthally polarized vortex beams were
      experimentally evaluated in native collagen tissue (porcine cornea). The findings
      are in good agreement with the theoretical predictions and display the
      possibility to probe the molecular orientation along the optical axis of samples
      with known nonlinear properties. The combination of simulations regarding the
      nonlinear response of materials and experiments with different sample
      orientations and present or non present z-polarization could help to increase the
      understanding of nonlinear signal formation in yet unstudied materials. 

PMID- 25071962
TI  - In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in
      breast cancer xenografts.
AB  - HER2-amplified (HER2 + ) breast cancers are treated with the anti-HER2 monoclonal
      antibody trastuzumab. Although trastuzumab reduces production of the angiogenic
      factor VEGF in HER2 + tumors, the acute and sustained effects of trastuzumab on
      the tumor vasculature are not understood fully, particularly in trastuzumab
      resistant tumors. We used mouse models of trastuzumab sensitive and trastuzumab
      resistant HER2 + breast cancers to measure dynamic changes in tumor microvessel
      density and hemoglobin oxygenation (sO2) in vivo using quantitative hyperspectral
      imaging at 2, 5, 9, and 14 days after antibody treatment. Further analysis
      quantified the distribution of microvessels into low and high oxygenation groups,
      and monitored changes in these distributions with trastuzumab treatment. Gold
      standard immunohistochemistry was performed to validate complementary markers of
      tumor cell and vascular response to treatment. Trastuzumab treatment in both
      responsive and resistant tumors resulted in decreased sO2 5 days after initial
      treatment when compared to IgG-treated controls (p<0.05). Importantly, responsive
      tumors showed significantly higher vessel density and significantly lower sO2
      than all other groups at 5 days post-treatment (p<0.05). Distribution analysis of
      vessel sO2 showed a significant (p<0.05) shift of highly oxygenated vessels
      towards lower oxygenation over the time-course in both trastuzumab-treated
      responsive and resistant tumors. This study suggests that longitudinal
      hyperspectral imaging of microvessel sO2 and density could distinguish
      trastuzumab-responsive from trastuzumab-resistant tumors, a finding that could be
      exploited in the post-neoadjuvant setting to guide post-surgical treatment
      decisions. 

PMID- 25071964
TI  - Modelling of diffraction grating based optical filters for fluorescence detection
      of biomolecules.
AB  - The detection of biomolecules based on fluorescence measurements is a powerful
      diagnostic tool for the acquisition of genetic, proteomic and cellular
      information. One key performance limiting factor remains the integrated optical
      filter, which is designed to reject strong excitation light while transmitting
      weak emission (fluorescent) light to the photodetector. Conventional filters have
      several disadvantages. For instance absorbing filters, like those made from
      amorphous silicon carbide, exhibit low rejection ratios, especially in the case
      of small Stokes' shift fluorophores (e.g. green fluorescent protein GFP with
      lambda exc = 480 nm and lambda em = 510 nm), whereas interference filters
      comprising many layers require complex fabrication. This paper describes an
      alternative solution based on dielectric diffraction gratings. These filters are
      not only highly efficient but require a smaller number of manufacturing steps.
      Using FEM-based optical modelling as a design optimization tool, three filtering
      concepts are explored: (i) a diffraction grating fabricated on the surface of an
      absorbing filter, (ii) a diffraction grating embedded in a host material with a
      low refractive index, and (iii) a combination of an embedded grating and an
      absorbing filter. Both concepts involving an embedded grating show high rejection
      ratios (over 100,000) for the case of GFP, but also high sensitivity to
      manufacturing errors and variations in the incident angle of the excitation
      light. Despite this, simulations show that a 60 times improvement in the
      rejection ratio relative to a conventional flat absorbing filter can be obtained
      using an optimized embedded diffraction grating fabricated on top of an absorbing
      filter. 

PMID- 25071963
TI  - Adaptive optics optical coherence tomography with dynamic retinal tracking.
AB  - Adaptive optics optical coherence tomography (AO-OCT) is a highly sensitive and
      noninvasive method for three dimensional imaging of the microscopic retina. Like
      all in vivo retinal imaging techniques, however, it suffers the effects of
      involuntary eye movements that occur even under normal fixation. In this study we
      investigated dynamic retinal tracking to measure and correct eye motion at KHz
      rates for AO-OCT imaging. A customized retina tracking module was integrated into
      the sample arm of the 2nd-generation Indiana AO-OCT system and images were
      acquired on three subjects. Analyses were developed based on temporal amplitude
      and spatial power spectra in conjunction with strip-wise registration to
      independently measure AO-OCT tracking performance. After optimization of the
      tracker parameters, the system was found to correct eye movements up to 100 Hz
      and reduce residual motion to 10 um root mean square. Between session precision
      was 33 um. Performance was limited by tracker-generated noise at high temporal
      frequencies. 

PMID- 25071965
TI  - Non-contact small animal fluorescence imaging system for simultaneous multi
      directional angular-dependent data acquisition.
AB  - We present a novel non-contact small animal fluorescent molecular tomography
      (FMT) imaging system. At the heart of the system is a new mirror-based imaging
      head that was designed to provide 360-degree measurement data from an entire
      animal surface in one step. This imaging head consists of two conical mirrors,
      which considerably reduce multiple back reflections between the animal and mirror
      surfaces. These back reflections are common in existing mirror-based imaging
      heads and tend to degrade the quality of raw measurement data. In addition, the
      introduction of a novel ray-transfer operator allows for the inclusion of the
      angular dependent data in the image reconstruction process, which results in
      higher image resolution. We describe in detail the system design and
      implementation of the hardware components as well as the transport-theory-based
      image reconstruction algorithm. Using numerical simulations, measurements on a
      well-defined phantom and a live animal, we evaluate the system performance and
      show the advantages of our approach. 

PMID- 25071966
TI  - Integral-geometry characterization of photobiomodulation effects on retinal
      vessel morphology.
AB  - The morphological characterization of quasi-planar structures represented by gray
      scale images is challenging when object identification is sub-optimal due to
      registration artifacts. We propose two alternative procedures that enhances
      object identification in the integral-geometry morphological image analysis (MIA)
      framework. The first variant streamlines the framework by introducing an active
      contours segmentation process whose time step is recycled as a multi-scale
      parameter. In the second variant, we used the refined object identification
      produced in the first variant to perform the standard MIA with exact dilation
      radius as multi-scale parameter. Using this enhanced MIA we quantify the extent
      of vaso-obliteration in oxygen-induced retinopathic vascular growth, the
      preventative effect (by photobiomodulation) of exposure during tissue development
      to near-infrared light (NIR, 670 nm), and the lack of adverse effects due to
      exposure to NIR light. 

PMID- 25071967
TI  - Noninvasive in-vehicle alcohol detection with wavelength-modulated differential
      photothermal radiometry.
AB  - This study describes the potential of wavelength-modulated differential
      photothermal radiometry (WM-DPTR) for non-invasive in-vehicle alcohol detection
      which can be of great importance in reducing alcohol-impaired driving. Ethanol
      content in the range of concern, 0-100 blood alcohol concentration (BAC) in water
      phantoms and blood serum diffused in human skin in vitro were measured with high
      sensitivity. The results show that the WM-DPTR system can be optimized for
      alcohol detection with the combination of two sensitivity-tuning parameters,
      amplitude ratio R and phase shift DeltaP. WM-DPTR has demonstrated the potential
      to be developed into a portable alcohol ignition interlock biosensor that could
      be fitted as a universal accessory in vehicles. 

PMID- 25071968
TI  - Controlled 3D rotation of biological cells using optical multiple-force clamps.
AB  - Controlled three-dimensional (3D) rotation of arbitrarily shaped objects in the
      observation space of optical microscopes is essential for realizing tomographic
      microscope imaging and offers great flexibility as a noncontact micromanipulation
      tool for biomedical applications. Herein, we present 3D rotational control of
      inhomogeneous biological samples using 3D optical multiple-force clamps based on
      time-shared scanning with a fast focus-tunable lens. For inhomogeneous samples
      with shape and optical anisotropy, we choose diatoms and their fragments, and
      demonstrate interactive and controlled 3D rotation about arbitrary axes in 3D
      Cartesian coordinates. We also outline the hardware setup and 3D rotation method
      for our demonstrations. 

PMID- 25071969
TI  - Magnetomotive optical coherence elastography using magnetic particles to induce
      mechanical waves.
AB  - Magnetic particles are versatile imaging agents that have found wide spread
      applicability in diagnostic, therapeutic, and rheology applications. In this
      study, we demonstrate that mechanical waves generated by a localized inclusion of
      magnetic nanoparticles can be used for assessment of the tissue viscoelastic
      properties using magnetomotive optical coherence elastography. We show these
      capabilities in tissue mimicking elastic and viscoelastic phantoms and in
      biological tissues by measuring the shear wave speed under magnetomotive
      excitation. Furthermore, we demonstrate the extraction of the complex shear
      modulus by measuring the shear wave speed at different frequencies and fitting to
      a Kelvin-Voigt model. 

PMID- 25071970
TI  - Quantifying tissue mechanical properties using photoplethysmography.
AB  - Photoplethysmography (PPG) is a non-invasive optical method that can be used to
      detect blood volume changes in the microvascular bed of tissue. The PPG signal
      comprises two components; a pulsatile waveform (AC) attributed to changes in the
      interrogated blood volume with each heartbeat, and a slowly varying baseline (DC)
      combining low frequency fluctuations mainly due to respiration and sympathetic
      nervous system activity. In this report, we investigate the AC pulsatile waveform
      of the PPG pulse for ultimate use in extracting information regarding the
      biomechanical properties of tissue and vasculature. By analyzing the rise time of
      the pulse in the diastole period, we show that PPG is capable of measuring
      changes in the Young's Modulus of tissue mimicking phantoms with a resolution of
      4 KPa in the range of 12 to 61 KPa. In addition, the shape of the pulse can
      potentially be used to diagnose vascular complications by differentiating
      upstream from downstream complications. A Windkessel model was used to model
      changes in the biomechanical properties of the circulation and to test the
      proposed concept. The modeling data confirmed the response seen in vitro and
      showed the same trends in the PPG rise and fall times with changes in compliance
      and vascular resistance. 

PMID- 25071971
TI  - Multiplexed coded illumination for Fourier Ptychography with an LED array
      microscope.
AB  - Fourier Ptychography is a new computational microscopy technique that achieves
      gigapixel images with both wide field of view and high resolution in both phase
      and amplitude. The hardware setup involves a simple replacement of the
      microscope's illumination unit with a programmable LED array, allowing one to
      flexibly pattern illumination angles without any moving parts. In previous work,
      a series of low-resolution images was taken by sequentially turning on each
      single LED in the array, and the data were then combined to recover a bandwidth
      much higher than the one allowed by the original imaging system. Here, we
      demonstrate a multiplexed illumination strategy in which multiple randomly
      selected LEDs are turned on for each image. Since each LED corresponds to a
      different area of Fourier space, the total number of images can be significantly
      reduced, without sacrificing image quality. We demonstrate this method
      experimentally in a modified commercial microscope. Compared to sequential
      scanning, our multiplexed strategy achieves similar results with approximately an
      order of magnitude reduction in both acquisition time and data capture
      requirements. 

PMID- 25071973
TI  - Noninvasive in vivo glucose sensing on human subjects using mid-infrared light.
AB  - Mid-infrared quantum cascade laser spectroscopy is used to noninvasively predict
      blood glucose concentrations of three healthy human subjects in vivo. We utilize
      a hollow-core fiber based optical setup for light delivery and collection along
      with a broadly tunable quantum cascade laser to obtain spectra from human
      subjects and use standard chemo-metric techniques (namely partial least squares
      regression) for prediction analysis. Throughout a glucose concentration range of
      80-160 mg/dL, we achieve clinically accurate predictions 84% of the time, on
      average. This work opens a new path to a noninvasive in vivo glucose sensor that
      would benefit the lives of hundreds of millions of diabetics worldwide. 

PMID- 25071972
TI  - Multi-modal label-free imaging based on a femtosecond fiber laser.
AB  - We demonstrate multi-mode microscopy based on a single femtosecond fiber laser.
      Coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS)
      and photothermal images can be obtained simultaneously with this simplified
      setup. Distributions of lipid and hemoglobin in sliced mouse brain samples and
      blood cells are imaged. The dependency of signal amplitude on the pump power and
      pump modulation frequency is characterized, which allows to isolate the impact
      from different contributions. 

PMID- 25071974
TI  - In-vivo imaging of psoriatic lesions with polarization multispectral dermoscopy
      and multiphoton microscopy.
AB  - Psoriasis is a skin autoimmune disease characterized by hyperkeratosis,
      hyperproliferation of the epidermis and dilatation of dermal papillary blood
      vessels. Healthy skin (5 volunteers) and psoriatic lesions (3 patients) were
      visualized in vivo, with high contrast and resolution, with a Polarization
      Multispectral Dermoscope and a Multiphoton Microscope. Psoriatic features were
      identified and quantified. The effective diameter of the superficial blood
      vessels was measured at 35.2 +/- 7.2 MUm and the elongated dermal papillae had an
      effective diameter of 64.2 +/- 22.6 MUm. The methodologies developed could be
      employed for quantitative diagnostic purposes and furthermore serve as a
      monitoring method of the effect of personalized treatments. 

PMID- 25071975
TI  - An effective nanosensor for organic molecules based on water-soluble
      mercaptopropionic acid-capped CdTe nanocrystals with potential application in
      high-throughput screening and high-resolution optical microscopy.
AB  - Specially-treated glass substrates coated with a thin film of water soluble
      mercaptopropionic acid (MPA) capped CdTe nanocrystals (NCs) were prepared and
      found to undergo photoluminescence changes by as much as 40% when micro-droplets
      of organic molecules were placed in the nanometer-range proximity of the NCs.
      This imaging technique involving close proximity between a nano-crystal and an
      organic molecule is found to provide a 2 * -3 * enhanced contrast ratio over the
      conventional method of fluorescence imaging. Photoluminescence of NCs is
      recoverable upon removal of the organic molecules, therefore validating these NCs
      as potential all-optical organic molecular nanosensors. Upon optimization and
      with proper instrumentation, these nano-crystals could eventually serve as point
      detectors for purposes of super-resolution optical microscopy. No solvents are
      required for the proposed sensing mechanism since all solutions were dried under
      argon flow. Fluorophores and fluorescent proteins were investigated, including
      fluorescein, Rhodamine 6G, and green fluorescent protein (GFP). Furthermore, NC
      photoluminescence changes were systematically quantified as a function of the
      solution pH and of the organic molecule concentration. Long duration (> 40
      minutes) continuous excitation studies were conducted in order to evaluate the
      reliability of the proposed sensing scheme. 

PMID- 25071976
TI  - Classification for breast cancer diagnosis with Raman spectroscopy.
AB  - In order to promote the development of the portable, low-cost and in vivo cancer
      diagnosis instrument, a miniature laser Raman spectrometer was employed to
      acquire the conventional Raman spectra for breast cancer detection in this paper.
      But it is difficult to achieve high discrimination accuracy. Then a novel method
      of adaptive weight k-local hyperplane (AWKH) is proposed to increase the
      classification accuracy. AWKH is an extension and improvement of K-local
      hyperplane distance nearest-neighbor (HKNN). It considers the features weights of
      the training data in the nearest neighbor selection and local hyperplane
      construction stage, which resolve the basic shortcoming of HKNN works well only
      for small values of the nearest-neighbor. Experimental results on Raman spectra
      of breast tissues in vitro show the proposed method can realize high
      classification accuracy. 

PMID- 25071977
TI  - Multi-photon excited luminescence of magnetic FePt core-shell nanoparticles.
AB  - We present magnetic FePt nanoparticles with a hydrophilic, inert, and
      biocompatible silico-tungsten oxide shell. The particles can be functionalized,
      optically detected, and optically manipulated. To show the functionalization the
      fluorescent dye NOPS was bound to the FePt core-shell nanoparticles with propyl
      triethoxy-silane linkers and fluorescence of the labeled particles were observed
      in ethanol (EtOH). In aqueous dispersion the NOPS fluorescence is quenched making
      them invisible using 1-photon excitation. However, we observe bright luminescence
      of labeled and even unlabeled magnetic core-shell nanoparticles with multi-photon
      excitation. Luminescence can be detected in the near ultraviolet and the full
      visible spectral range by near infrared multi-photon excitation. For optical
      manipulation, we were able to drag clusters of particles, and maybe also single
      particles, by a focused laser beam that acts as optical tweezers by inducing an
      electric dipole in the insulated metal nanoparticles. In a first application, we
      show that the luminescence of the core-shell nanoparticles is bright enough for
      in vivo multi-photon imaging in the mouse neocortex down to cortical layer 5. 

PMID- 25071978
TI  - Neuroblastoma of the elderly, an oncologist's nightmare: case presentation,
      literature review and SEER database analysis.
AB  - Neuroblastoma is considered a pediatric malignancy as over 95% of cases are
      diagnosed in patients <=10 years old. This cancer is extremely rare in elderly
      patients. We conducted a Surveillance, Epidemiology, and End Results (SEER)
      database analysis in the USA between 1973-2007 that revealed only 35 elderly
      patients (>60 years of age) with neuroblastoma of whom only 2 patients had
      primary mediastinal neuroblastoma. There is a paucity of treatment and survival
      outcomes data for the elderly owing to the rarity of neuroblastoma in this
      population. Currently there are no standard guidelines or protocols for treatment
      of adult neuroblastoma. We report a rare and challenging case of an 86-year old
      patient presenting with mediastinal neuroblastoma and syndrome of inappropriate
      antidiuretic hormone secretion (SIADH) successfully treated with resection.
      Herein, we also provide a review of the literature and updated survival data on
      neuroblastoma based on results of our SEER database review. 

PMID- 25071979
TI  - Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death.
AB  - Established tumors are typified by an immunosuppresive microenvironment.
      Countering this naturally occurring phenomenon, emerging evidence suggests that
      radiation promotes a proimmunogenic milieu within the tumor capable of
      stimulating host cancer-specific immune responses. Three cryptic immunogenic
      components of cytotoxic-agent induced cell death-namely, calreticulin cell
      surface exposure, the release of high mobility group box 1 (HMGB1) protein, and
      the liberation of ATP-have been previously shown to be critical for dendritic
      cell (DC) activation and effector T-cell priming. Thus, these immune-mobilizing
      components commonly presage tumor rejection in response to treatment. We
      initially set out to address the hypothesis that radiation-induced immunogenic
      cell death (ICD) is dose-dependent. Next, we hypothesized that radiation would
      enhance chemotherapy-induced ICD when given concomitantly, as suggested by the
      favorable clinical outcomes observed in response to analogous concurrent
      chemoradiation regimens. Thus, we designed an in vitro assay to examine the 3
      hallmark features of ICD at clinically relevant doses of radiation. We then
      tested the immunogenic-death inducing effects of radiation combined with
      carboplatin or paclitaxel, focusing on these combinations to mimic chemoradiation
      regimens actually used in clinical trials of early stage triple negative
      [NCT0128953/NYU-10-01969] and locally advanced [NYU-06209] breast cancer
      patients, respectively. Despite the obvious limitations of an in vitro model,
      radiotherapy produced both a dose-dependent induction and chemotherapeutic
      enhancement of ICD. These findings provide preliminary evidence that ICD
      stimulated by either high-dose radiotherapy alone, or concurrent chemoradiation
      regimens, may contribute to the establishment of a peritumoral proimmunogenic
      milieu.

PMID- 25071980
TI  - Impact of Combat and Social Support on PTSD and Alcohol Consumption in OEF/OIF
      Veterans.
AB  - We tested buffering and direct effect theories of social support to determine if
      combat exposure level moderated relationships between two aspects of social
      support (unit cohesion and postdeployment support) and two outcomes (PTSD and
      alcohol consumption) in 69 hazardous-drinking OEF/OIF veterans (65% Caucasian,
      91% male). Combat exposure moderated the relationship between unit cohesion and
      PTSD. Unit cohesion was related to lower PTSD severity only for veterans with
      less severe combat exposure. Higher postdeployment support was related to less
      severe PTSD for all veterans. Alcohol consumption results were not significant.

PMID- 25071982
TI  - Neighbourhood walkability, leisure-time and transport-related physical activity
      in a mixed urban-rural area.
AB  - Objectives. To develop a walkability index specific to mixed rural/suburban
      areas, and to explore the relationship between walkability scores and leisure
      time physical activity. Methods. Respondents were geocoded with 500 m and 1,000 m
      buffer zones around each address. A walkability index was derived from
      intersections, residential density, and land-use mix according to built
      environment measures. Multivariable logistic regression models were used to
      quantify the association between the index and physical activity levels. Analyses
      used cross-sectional data from the 2007-2008 Canadian Community Health Survey (n
      = 1158; >=18 y). Results. Respondents living in highly walkable 500 m buffer
      zones (upper quartiles of the walkability index) were more likely to walk or
      cycle for leisure than those living in low-walkable buffer zones (quartile 1).
      When a 1,000 m buffer zone was applied, respondents in more walkable
      neighbourhoods were more likely to walk or cycle for both leisure-time and
      transport-related purposes. Conclusion. Developing a walkability index can assist
      in exploring the associations between measures of the built environment and
      physical activity to prioritize neighborhood change. 

PMID- 25071981
TI  - Anatomical and biomechanical traits of broiler chickens across ontogeny. Part I.
      Anatomy of the musculoskeletal respiratory apparatus and changes in organ size.
AB  - Genetic selection for improved meat yields, digestive efficiency and growth rates
      have transformed the biology of broiler chickens. Modern birds undergo a 50-fold
      multiplication in body mass in just six weeks, from hatching to slaughter weight.
      However, this selection for rapid growth and improvements in broiler productivity
      is also widely thought to be associated with increased welfare problems as many
      birds suffer from leg, circulatory and respiratory diseases. To understand growth
      related changes in musculoskeletal and organ morphology and respiratory skeletal
      development over the standard six-week rearing period, we present data from post
      hatch cadaveric commercial broiler chickens aged 0, 2, 4 and 6 weeks. The heart,
      lungs and intestines decreased in size for hatch to slaughter weight when
      considered as a proportion of body mass. Proportional liver size increased in the
      two weeks after hatch but decreased between 2 and 6 weeks. Breast muscle mass on
      the other hand displayed strong positive allometry, increasing in mass faster
      than the increase in body mass. Contrastingly, less rapid isometric growth was
      found in the external oblique muscle, a major respiratory muscle that moves the
      sternum dorsally during expiration. Considered together with the relatively slow
      ossification of elements of the respiratory skeleton, it seems that rapid growth
      of the breast muscles might compromise the efficacy of the respiratory apparatus.
      Furthermore, the relative reduction in size of the major organs indicates that
      selective breeding in meat-producing birds has unintended consequences that may
      bias these birds toward compromised welfare and could limit further improvements
      in meat-production and feed efficiency. 

PMID- 25071983
TI  - Local norms of cheating and the cultural evolution of crime and punishment: a
      study of two urban neighborhoods.
AB  - The prevalence of antisocial behavior varies across time and place. The
      likelihood of committing such behavior is affected by, and also affects, the
      local social environment. To further our understanding of this dynamic process,
      we conducted two studies of antisocial behavior, punishment, and social norms.
      These studies took place in two neighborhoods in Newcastle Upon Tyne, England.
      According to a previous study, Neighborhood A enjoys relatively low frequencies
      of antisocial behavior and crime and high levels of social capital. In contrast,
      Neighborhood B is characterized by relatively high frequencies of antisocial
      behavior and crime and low levels of social capital. In Study 1, we used an
      economic game to assess neighborhood differences in theft, third-party punishment
      (3PP) of theft, and expectation of 3PP. Participants also reported their
      perceived neighborhood frequency of cooperative norm violation ("cheating").
      Participants in Neighborhood B thought that their neighbors commonly cheat but
      did not condone cheating. They stole more money from their neighbors in the game,
      and were less punitive of those who did, than the residents of Neighborhood A.
      Perceived cheating was positively associated with theft, negatively associated
      with the expectation of 3PP, and central to the neighborhood difference. Lower
      trust in one's neighbors and a greater subjective value of the monetary cost of
      punishment contributed to the reduced punishment observed in Neighborhood B. In
      Study 2, we examined the causality of cooperative norm violation on expectation
      of 3PP with a norms manipulation. Residents in Neighborhood B who were informed
      that cheating is locally uncommon were more expectant of 3PP. In sum, our results
      provide support for three potentially simultaneous positive feedback mechanisms
      by which the perception that others are behaving antisocially can lead to further
      antisocial behavior: (1) motivation to avoid being suckered, (2) decreased
      punishment of antisocial behavior, and (3) decreased expectation of punishment of
      antisocial behavior. Consideration of these mechanisms and of norm psychology
      will help us to understand how neighborhoods can descend into an antisocial
      culture and get stuck there. 

PMID- 25071984
TI  - Measurement uncertainties in quantifying aeolian mass flux: evidence from wind
      tunnel and field site data.
AB  - Aeolian sediment traps are widely used to estimate the total volume of wind
      driven sediment transport, but also to study the vertical mass distribution of a
      saltating sand cloud. The reliability of sediment flux estimations from such
      measurements are dependent upon the specific configuration of the measurement
      compartments and the analysis approach used. In this study, we analyse the
      uncertainty of these measurements by investigating the vertical cumulative
      distribution and relative sediment flux derived from both wind tunnel and field
      studies. Vertical flux data was examined using existing data in combination with
      a newly acquired dataset; comprising meteorological data and sediment fluxes from
      six different events, using three customized catchers at Ameland beaches in
      northern Netherlands. Fast-temporal data collected in a wind tunnel shows that
      the median transport height has a scattered pattern between impact and fluid
      threshold, that increases linearly with shear velocities above the fluid
      threshold. For finer sediment, a larger proportion was transported closer to the
      surface compared to coarser sediment fractions. It was also shown that errors
      originating from the distribution of sampling compartments, specifically the
      location of the lowest sediment trap relative to the surface, can be identified
      using the relative sediment flux. In the field, surface conditions such as
      surface moisture, surface crusts or frozen surfaces have a more pronounced but
      localized effect than shear velocity. Uncertainty in aeolian mass flux estimates
      can be reduced by placing multiple compartments in closer proximity to the
      surface. 

PMID- 25071985
TI  - Disjoint combinations profiling (DCP): a new method for the prediction of
      antibody CDR conformation from sequence.
AB  - The accurate prediction of the conformation of Complementarity-Determining
      Regions (CDRs) is important in modelling antibodies for protein engineering
      applications. Specifically, the Canonical paradigm has proved successful in
      predicting the CDR conformation in antibody variable regions. It relies on
      canonical templates which detail allowed residues at key positions in the
      variable region framework or in the CDR itself for 5 of the 6 CDRs. While no
      templates have as yet been defined for the hypervariable CDR-H3, instead,
      reliable sequence rules have been devised for predicting the base of the CDR-H3
      loop. Here a new method termed Disjoint Combinations Profiling (DCP) is
      presented, which contributes a considerable advance in the prediction of CDR
      conformations. This novel method is explained and compared with canonical
      templates and sequence rules in a 3-way blind prediction. DCP achieved 93%
      accuracy over 951 blind predictions and showed an improvement in cumulative
      accuracy compared to predictions with canonical templates or sequence rules. In
      addition to its overall improvement in prediction accuracy, it is suggested that
      DCP is open to better implementations in the future and that it can improve as
      more antibody structures are deposited in the databank. In contrast, it is argued
      that canonical templates and sequence rules may have reached their peak. 

PMID- 25071986
TI  - A complete, multi-level conformational clustering of antibody complementarity
      determining regions.
AB  - Classification of antibody complementarity-determining region (CDR) conformations
      is an important step that drives antibody modelling and engineering, prediction
      from sequence, directed mutagenesis and induced-fit studies, and allows
      inferences on sequence-to-structure relations. Most of the previous work
      performed conformational clustering on a reduced set of structures or after
      application of various structure pre-filtering criteria. In this study, it was
      judged that a clustering of every available CDR conformation would produce a
      complete and redundant repertoire, increase the number of sequence examples and
      allow better decisions on structure validity in the future. In order to cope with
      the potential increase in data noise, a first-level statistical clustering was
      performed using structure superposition Root-Mean-Square Deviation (RMSD) as a
      distance-criterion, coupled with second- and third-level clustering that employed
      Ramachandran regions for a deeper qualitative classification. The classification
      of a total of 12,712 CDR conformations is thus presented, along with rich
      annotation and cluster descriptions, and the results are compared to previous
      major studies. The present repertoire has procured an improved image of our
      current CDR Knowledge-Base, with a novel nesting of conformational sensitivity
      and specificity that can serve as a systematic framework for improved prediction
      from sequence as well as a number of future studies that would aid in knowledge
      based antibody engineering such as humanisation. 

PMID- 25071987
TI  - The first juvenile specimens of Plateosaurus engelhardti from Frick, Switzerland:
      isolated neural arches and their implications for developmental plasticity in a
      basal sauropodomorph.
AB  - The dinosaur Plateosaurus engelhardti is the most abundant dinosaur in the Late
      Triassic of Europe and the best known basal sauropodomorph. Plateosaurus
      engelhardti was one of the first sauropodomorph dinosaurs to display a large body
      size. Remains can be found in the Norian stage of the Late Triassic in over 40
      localities in Central Europe (France, Germany, and Switzerland) and in Greenland.
      Since the first discovery of P. engelhardti no juvenile specimens of this species
      had been described in detail. Here we describe the first remains of juvenile
      individuals, isolated cervical and dorsal neural arches from Switzerland. These
      were separated postmortem from their respective centra because of unfused
      neurocentral sutures. However the specimens share the same neural arch morphology
      found in adults. Morphometric analysis suggests body lengths of the juvenile
      individuals that is greater than those of most adult specimens. This supports the
      hypothesis of developmental plasticity in Plateosaurus engelhardti that
      previously had been based on histological data only. Alternative hypotheses for
      explaining the poor correlation between ontogenetic stage and size in this taxon
      are multiple species or sexual morphs with little morphological variance or time
      averaging of individuals from populations differing in body size. 

PMID- 25071988
TI  - Automated analysis of invadopodia dynamics in live cells.
AB  - Multiple cell types form specialized protein complexes that are used by the cell
      to actively degrade the surrounding extracellular matrix. These structures are
      called podosomes or invadopodia and collectively referred to as invadosomes. Due
      to their potential importance in both healthy physiology as well as in
      pathological conditions such as cancer, the characterization of these structures
      has been of increasing interest. Following early descriptions of invadopodia,
      assays were developed which labelled the matrix underneath metastatic cancer
      cells allowing for the assessment of invadopodia activity in motile cells.
      However, characterization of invadopodia using these methods has traditionally
      been done manually with time-consuming and potentially biased quantification
      methods, limiting the number of experiments and the quantity of data that can be
      analysed. We have developed a system to automate the segmentation, tracking and
      quantification of invadopodia in time-lapse fluorescence image sets at both the
      single invadopodia level and whole cell level. We rigorously tested the ability
      of the method to detect changes in invadopodia formation and dynamics through the
      use of well-characterized small molecule inhibitors, with known effects on
      invadopodia. Our results demonstrate the ability of this analysis method to
      quantify changes in invadopodia formation from live cell imaging data in a high
      throughput, automated manner. 

PMID- 25071989
TI  - The role of fragmentation and landscape changes in the ecological release of
      common nest predators in the Neotropics.
AB  - Loss of large mammalian carnivores may allow smaller mesopredators to become
      abundant and threaten other community members. There is considerable debate about
      mesopredator release and the role that other potential factors such as landscape
      variables and human alterations to land cover lead to increased mesopredator
      abundance. We used camera traps to detect four mesopredators (tayra, Eira
      barbara; white-nosed coati, Nasua narica; northern raccoon, Procyon lotor; and
      common opossum, Didelphis opossum) in a biological corridor in Costa Rica to
      estimate habitat covariates that influenced the species' detection and
      occurrence. We selected these mesopredators because as semi-arboreal species they
      might be common nest predators, posing a serious threat to resident and migratory
      songbirds. Pineapple production had a pronounced positive effect on the
      detectability of tayras, while forest cover had a negative effect on the
      detection of coatis. This suggests that abundance might be elevated due to the
      availability of agricultural food resources and foraging activities are
      concentrated in forest fragments and pineapple edge habitats. Raccoon and opossum
      models exhibited little influence on detection from habitat covariates.
      Occurrence models did not suggest any significant factors influencing site use by
      nest predators, revealing that all four species are habitat generalists adapted
      to co-existing in human altered landscapes. Furthermore, fragmentation and land
      cover changes may predispose nesting birds, herpetofauna, and small mammals to
      heightened predation risk by mesopredators in the Neotropics. 

PMID- 25071990
TI  - Modified generalized method of moments for a robust estimation of polytomous
      logistic model.
AB  - The maximum likelihood estimation (MLE) method, typically used for polytomous
      logistic regression, is prone to bias due to both misclassification in outcome
      and contamination in the design matrix. Hence, robust estimators are needed. In
      this study, we propose such a method for nominal response data with continuous
      covariates. A generalized method of weighted moments (GMWM) approach is developed
      for dealing with contaminated polytomous response data. In this approach,
      distances are calculated based on individual sample moments. And Huber weights
      are applied to those observations with large distances. Mellow-type weights are
      also used to downplay leverage points. We describe theoretical properties of the
      proposed approach. Simulations suggest that the GMWM performs very well in
      correcting contamination-caused biases. An empirical application of the GMWM
      estimator on data from a survey demonstrates its usefulness. 

PMID- 25071991
TI  - Development of allele-specific multiplex PCR to determine the length of poly-T in
      intron 8 of CFTR.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis
      has been implemented for Cystic Fibrosis (CF) carrier screening, and molecular
      diagnosis of CF and congenital bilateral absence of the vas deferens (CBAVD).
      Although poly-T allele analysis in intron 8 of CFTR is required when a patient is
      positive for R117H, it is not recommended for routine carrier screening.
      Therefore, commercial kits for CFTR mutation analysis were designed either to
      mask the poly-T allele results, unless a patient is R117H positive, or to have
      the poly-T analysis as a standalone reflex test using the same commercial
      platform. There are other standalone assays developed to detect poly-T alleles,
      such as heteroduplex analysis, High Resolution Melting (HRM) curve analysis,
      allele-specific PCR (AS-PCR) and Sanger sequencing. In this report, we developed
      a simple and easy-to-implement multiplex AS-PCR assay using unlabeled standard
      length primers, which can be used as a reflex or standalone test for CFTR poly-T
      track analysis. Out of 115 human gDNA samples tested, results from our new AS-PCR
      matched to the previous known poly-T results or results from Sanger sequencing. 

PMID- 25071992
TI  - Augmented reality in healthcare education: an integrative review.
AB  - Background. The effective development of healthcare competencies poses great
      educational challenges. A possible approach to provide learning opportunities is
      the use of augmented reality (AR) where virtual learning experiences can be
      embedded in a real physical context. The aim of this study was to provide a
      comprehensive overview of the current state of the art in terms of user
      acceptance, the AR applications developed and the effect of AR on the development
      of competencies in healthcare. Methods. We conducted an integrative review.
      Integrative reviews are the broadest type of research review methods allowing for
      the inclusion of various research designs to more fully understand a phenomenon
      of concern. Our review included multi-disciplinary research publications in
      English reported until 2012. Results. 2529 research papers were found from ERIC,
      CINAHL, Medline, PubMed, Web of Science and Springer-link. Three qualitative, 20
      quantitative and 2 mixed studies were included. Using a thematic analysis, we've
      described three aspects related to the research, technology and education. This
      study showed that AR was applied in a wide range of topics in healthcare
      education. Furthermore acceptance for AR as a learning technology was reported
      among the learners and its potential for improving different types of
      competencies. Discussion. AR is still considered as a novelty in the literature.
      Most of the studies reported early prototypes. Also the designed AR applications
      lacked an explicit pedagogical theoretical framework. Finally the learning
      strategies adopted were of the traditional style 'see one, do one and teach one'
      and do not integrate clinical competencies to ensure patients' safety. 

PMID- 25071993
TI  - Computational development of rubromycin-based lead compounds for HIV-1 reverse
      transcriptase inhibition.
AB  - The binding of several rubromycin-based ligands to HIV1-reverse transcriptase was
      analyzed using molecular docking and molecular dynamics simulations. MM-PBSA
      analysis and examination of the trajectories allowed the identification of
      several promising compounds with predicted high affinity towards reverse
      transcriptase mutants which have proven resistant to current drugs. Important
      insights on the complex interplay of factors determining the ability of ligands
      to selectively target each mutant have been obtained. 

PMID- 25071994
TI  - Is painting by elephants in zoos as enriching as we are led to believe?
AB  - The relationship between the activity of painting and performance of stereotyped
      and other stress-related behaviour was investigated in four captive Asian
      elephants at Melbourne Zoo, Australia. The activity involved the elephant being
      instructed to paint on a canvas by its keeper in front of an audience. Painting
      by elephants in zoos is commonly believed to be a form of enrichment, but this
      assumption had not been based on any systematic research. If an activity is
      enriching we would expect stress-related behaviour to be reduced but we found no
      evidence of the elephants anticipating the painting activity and no effect on the
      performance of stereotyped or other stress-related behaviour either before or
      after the painting session. This indicates that the activity does not fulfil one
      of the main aims of enrichment. However, if an elephant was not selected to paint
      on a given day this was associated with higher levels of non-interactive
      behaviour, a possible indicator of stress. Behavioural observations associated
      with ear, eye and trunk positions during the painting session showed that the
      elephant's attentiveness to the painting activity or to the keeper giving
      instruction varied between individuals. Apart from positive reinforcement from
      the keeper, the results indicated that elephants gain little enrichment from the
      activity of painting. Hence, the benefits of this activity appear to be limited
      to the aesthetic appeal of these paintings to the people viewing them. 

PMID- 25071995
TI  - Hemigrapsus sanguineus in Long Island salt marshes: experimental evaluation of
      the interactions between an invasive crab and resident ecosystem engineers.
AB  - The invasive Asian shore crab, Hemigrapsus sanguineus, has recently been observed
      occupying salt marshes, a novel environment for this crab species. As it invades
      this new habitat, it is likely to interact with a number of important salt marsh
      species. To understand the potential effects of H. sanguineus on this ecosystem,
      interactions between this invasive crab and important salt marsh ecosystem
      engineers were examined. Laboratory experiments demonstrated competition for
      burrows between H. sanguineus and the native fiddler crab, Uca pugilator. Results
      indicate that H. sanguineus is able to displace an established fiddler crab from
      its burrow. Feeding experiments revealed that the presence of H. sanguineus has a
      significantly negative impact on the number as well as the biomass of ribbed
      mussels (Geukensia demissa) consumed by the green crab, Carcinus maenas, although
      this only occurred at high predator densities. In addition, when both crabs
      foraged together, there was a significant shift in the size of mussels consumed.
      These interactions suggests that H. sanguineus may have long-term impacts and
      wide-ranging negative effects on the saltmarsh ecosystem. 

PMID- 25071996
TI  - Anatomical and biomechanical traits of broiler chickens across ontogeny. Part II.
      Body segment inertial properties and muscle architecture of the pelvic limb.
AB  - In broiler chickens, genetic success for desired production traits is often
      shadowed by welfare concerns related to musculoskeletal health. Whilst these
      concerns are clear, a viable solution is still elusive. Part of the solution lies
      in knowing how anatomical changes in afflicted body systems that occur across
      ontogeny influence standing and moving. Here, to demonstrate these changes we
      quantify the segment inertial properties of the whole body, trunk (legs removed)
      and the right pelvic limb segments of five broilers at three different age groups
      across development. We also consider how muscle architecture (mass, fascicle
      length and other properties related to mechanics) changes for selected muscles of
      the pelvic limb. All broilers used had no observed lameness, but we document the
      limb pathologies identified post mortem, since these two factors do not always
      correlate, as shown here. The most common leg disorders, including bacterial
      chondronecrosis with osteomyelitis and rotational and angular deformities of the
      lower limb, were observed in chickens at all developmental stages. Whole limb
      morphology is not uniform relative to body size, with broilers obtaining large
      thighs and feet between four and six weeks of age. This implies that the
      energetic cost of swinging the limbs is markedly increased across this growth
      period, perhaps contributing to reduced activity levels. Hindlimb bone length
      does not change during this period, which may be advantageous for increased
      stability despite the increased energetic costs. Increased pectoral muscle growth
      appears to move the centre of mass cranio-dorsally in the last two weeks of
      growth. This has direct consequences for locomotion (potentially greater limb
      muscle stresses during standing and moving). Our study is the first to measure
      these changes in the musculoskeletal system across growth in chickens, and
      reveals how artificially selected changes of the morphology of the pectoral
      apparatus may cause deficits in locomotion. 

PMID- 25071997
TI  - Local domestication of lactic acid bacteria via cassava beer fermentation.
AB  - Cassava beer, or chicha, is typically consumed daily by the indigenous Shuar
      people of the Ecuadorian Amazon. This traditional beverage made from cassava
      tuber (Manihot esculenta) is thought to improve nutritional quality and flavor
      while extending shelf life in a tropical climate. Bacteria responsible for chicha
      fermentation could be a source of microbes for the human microbiome, but little
      is known regarding the microbiology of chicha. We investigated bacterial
      community composition of chicha batches using Illumina high-throughput
      sequencing. Fermented chicha samples were collected from seven Shuar households
      in two neighboring villages in the Morona-Santiago region of Ecuador, and the
      composition of the bacterial communities within each chicha sample was determined
      by sequencing a region of the 16S ribosomal gene. Members of the genus
      Lactobacillus dominated all samples. Significantly greater phylogenetic
      similarity was observed among chicha samples taken within a village than those
      from different villages. Community composition varied among chicha samples, even
      those separated by short geographic distances, suggesting that ecological and/or
      evolutionary processes, including human-mediated factors, may be responsible for
      creating locally distinct ferments. Our results add to evidence from other
      fermentation systems suggesting that traditional fermentation may be a form of
      domestication, providing endemic beneficial inocula for consumers, but additional
      research is needed to identify the mechanisms and extent of microbial dispersal. 

PMID- 25071998
TI  - Attrition in a 30-year follow-up of a perinatal birth risk cohort: factors change
      with age.
AB  - Background. Attrition is a major cause of potential bias in longitudinal studies
      and clinical trials. Attrition rate above 20% raises concern of the reliability
      of the results. Few studies have looked at the factors behind attrition in follow
      ups spanning decades. Methods. We analyzed attrition and associated factors of a
      30-year follow-up cohort of subjects who were born with perinatal risks for
      neurodevelopmental disorders. Attrition rates were calculated at different stages
      of follow-up and differences between responders and non-responders were tested.
      To find combinations of variables influencing attrition and investigate their
      relative importance at birth, 5, 9, 16 and 30 years of follow-up we used the
      random forest classification. Results. Initial loss of potential participants was
      13%. Attrition was 16% at five, 24% at nine, 35% at 16 and 46% at 30 years. The
      only group difference that emerged between responders and non-responders was in
      socioeconomic status (SES). The variables identified by random forest
      classification analysis were classified into Birth related, Development related
      and SES related. Variables from all these categories contributed to attrition,
      but SES related variables were less important than birth and development
      associated variables. Classification accuracy ranged between 0.74 and 0.96
      depending on age. Discussion. Lower SES is linked to attrition in many studies.
      Our results point to the importance of the growth and development related factors
      in a longitudinal study. Parents' decisions to participate depend on the
      characteristics of the child. The same association was also seen when the child,
      now grown up, decided to participate at 30 years. In addition, birth related
      medical variables are associated with the attrition still at the age of 30. Our
      results using a data mining approach suggest that attrition in longitudinal
      studies is influenced by complex interactions of a multitude of variables, which
      are not necessarily evident using other multivariate techniques. 

PMID- 25071999
TI  - HIV-positive parents, HIV-positive children, and HIV-negative children's
      perspectives on disclosure of a parent's and child's illness in Kenya.
AB  - HIV disclosure from parent to child is complex and challenging to HIV-positive
      parents and healthcare professionals. The purpose of the study was to understand
      the lived experiences of HIV-positive parents and their children during the
      disclosure process in Kenya. Sixteen HIV-positive parents, seven HIV-positive
      children, and five HIV-negative children completed semistructured, in-depth
      interviews. Data were analyzed using the Van Kaam method; NVivo 8 software was
      used to assist data analysis. We present data on the process of disclosure based
      on how participants recommended full disclosure be approached to HIV-positive and
      negative children. Participants recommended disclosure as a process starting at
      five years with full disclosure delivered at 10 years when the child was capable
      of understanding the illness, or by 14 years when the child was mature enough to
      receive the news if full disclosure had not been conducted earlier. Important
      considerations at the time of full disclosure included the parent's and/or
      child's health statuses, number of infected family members' illnesses to be
      disclosed to the child, child's maturity and understanding level, and the person
      best suited to deliver full disclosure to the child. The results also revealed it
      was important to address important life events such as taking a national school
      examination during disclosure planning and delivery. Recommendations are made for
      inclusion into HIV disclosure guidelines, manuals, and programs in resource-poor
      nations with high HIV prevalence. 

PMID- 25072000
TI  - Trends in Bone Morphogenetic Protein Usage since the U.S. Food and Drug
      Administration Advisory in 2008: What Happens to Physician Practices When the
      Food and Drug Administration Issues an Advisory?
AB  - Study Design Retrospective cross-sectional study of spinal procedures from 2002
      to 2010 using the Nationwide Inpatient Sample database. Objective To determine
      the patterns of bone morphogenetic protein (BMP) usage in fusion surgery before
      and after the U.S. Food and Drug Administration (FDA) 2008 advisory for the
      anterior cervical spine to understand how advisories affect U.S. physician
      practices. Methods Procedures were identified through International
      Classification of Diseases, Ninth Revision procedure codes and were plotted over
      time based on fusion procedure type, site, and area of fusion. U.S. national
      trends were approximated by polynomial regression analysis. Results The majority
      of the data trends of BMP usage reflect a second-order polynomial model. BMP
      usage in anterior cervical spine fusion procedures plateaued during the fourth
      quarter of 2007. The most apparent change in trend was noted in BMP usage pre-
      and postadvisory in the analysis of anterior cervical spine fusions. BMP
      percentage of use decreased in this area by 5% from the time of the FDA advisory
      to the fourth quarter of 2010. Conclusions The decrease in BMP usage in anterior
      cervical spinal fusion procedures coincided with the timing of the FDA advisory.
      The fact that BMP continued to be used in cervical spine fusion procedures, even
      at lower rates, despite the advisory, may reflect the availability of new
      clinical information that could lessen complications (i.e., lower BMP dose,
      perioperative steroids, BMP containment). Furthermore, factors like the natural
      ceiling effect of use or demand for new technology, complications, prohibitive
      institutional costs, access to information, and insurance compensation may have
      all contributed to the BMP usage trends observed. 

PMID- 25072001
TI  - Preoperative predictors of patient satisfaction with outcome after cervical
      laminoplasty.
AB  - Study design Prospective cohort study. Objective The purpose of the present study
      was to identify the predictors of patient satisfaction with outcome after
      cervical laminoplasty for compressive cervical myelopathy. Methods A cohort of
      143 patients with compressive myelopathy who underwent cervical double-door
      laminoplasty between 2008 and 2011 was studied prospectively. The principal
      outcome was patient satisfaction with outcome at 1 year after surgery. Patient
      satisfaction was graded on an ordinal scale from 1 to 7. Subjective health
      related quality of life (QOL) and objective disease-specific outcome was measured
      by Short Form-36 (SF-36) and the Japanese Orthopaedic Association (JOA) score,
      respectively, before surgery and at 1-year follow-up. We evaluated the
      association between patient satisfaction at 1-year follow-up and various baseline
      parameters, including patient demographics, duration of symptoms, comorbidities,
      imaging findings, JOA score, and SF-36 scores. Results A total of 116 patients
      completed subjective and objective follow-up for a minimum of 1 year. Of 116
      patients, 95 patients (81.9%) were satisfied with the outcome ("satisfied a
      little" or more). The unsatisfied group ("neutral" or less) showed significantly
      lower baseline SF-36 scores in bodily pain (BP), general health perceptions (GH),
      and vitality (VT) domains compared with the satisfied group. At the 1-year follow
      up, SF-36 scores showed significant differences between the groups in all eight
      domains, whereas the JOA score showed no significant difference. Conclusions
      Lower baseline QOL measured by SF-36 scores, specifically in BP, GH, and VT
      domains, are associated with lower satisfaction with outcome after cervical
      laminoplasty. 

PMID- 25072002
TI  - The Incidence of Adjacent Segment Breakdown in Polysegmental Thoracolumbar
      Fusions of Three or More Levels with Minimum 5-Year Follow-up.
AB  - Study Design Retrospective cohort study. Objective To identify the incidence of
      adjacent segment pathology (ASP) after thoracolumbar fusion of three or more
      levels, the risk factors for the development of ASP, and the need for further
      surgical intervention in this particular patient population. Methods A
      retrospective analysis of a prospective surgical database identified 217 patients
      receiving polysegmental (>= 3 levels) spinal fusion with minimum 5-year follow
      up. Risk factors were evaluated, and the following data were obtained from the
      review of radiographs and charts: radiographic measures-levels fused, fusion
      status, presence of ASP; clinical measures-patient assessment, Oswestry
      Disability Index (ODI), and the need for further surgery. Results The incidence
      of radiographic ASP (RASP) was 29%; clinical or symptomatic ASP (CASP), 18%; and
      those requiring surgery, 9%. Correlation was observed between ODI and ASP,
      symptomatic ASP, and need for revision surgery. Age, preoperative degenerative
      diagnosis, and absence of fusion demonstrated significant association to ASP.
      Conclusions ASP was observed in a significant number of patients receiving
      polysegmental fusion of three or more levels. ODI scores correlated to RASP,
      CASP, and the need for revision surgery. 

PMID- 25072003
TI  - One-stage biopsy, debridement, reconstruction, and stabilization of pyogenic
      vertebral osteomyelitis.
AB  - Study Design Retrospective cohort study. Objective To evaluate whether the
      proposed one-stage biopsy, culture, debridement, and reconstruction with
      stabilization strategy is a viable option for pyogenic vertebral osteomyelitis
      (PVO). PVO is increasing in frequency globally, particularly in immunologically
      compromised individuals. Typically, biopsy and culture sensitivity followed by
      staged surgery and long-term antibiotic therapy is the mainstay of therapy.
      Methods This is a study of a group of 32 consecutive cases of PVO
      (spondylodiskitis) treated in our institution from 2010 to 2012. All cases had
      one-stage biopsy, culture sensitivity, debridement, reconstruction with iliac
      bone graft, and stabilization with titanium implants. The mean age in this series
      was 51 years, and the male-to-female ratio was 2.2:1. Approximately 50% of the
      patients had impaired immunity status. The commonest organism isolated was
      Pseudomonas aeruginosa. Culture-specific antibiotics were given for a minimum of
      6 weeks to all patients. The follow-up period ranged from 6 months to a maximum
      of 2 years. All patients were assessed for wound healing, recurrence of
      infection, deformity progression, pain, and healing by radiologic and biochemical
      parameters. No generic or disease-specific outcome tools were used for this
      study. Results All patients had good wound healing, although there was one case
      of superficial infection that was resolved with debridement. There were two
      implant failures with pseudarthrosis and one localized kyphosis in this series.
      Conclusions The one-stage technique of biopsy, debridement, bone grafting, and
      stabilization can be recommended for most cases of PVO. 

PMID- 25072004
TI  - Ependymal cyst presenting with lhermitte sign.
AB  - Study Design Case report and review of the literature. Objective To present an
      unusual case of conus medullaris ependymal cyst. Methods This is a case of a 41
      year-old woman with a diagnosis of ependymal cyst who presented with a history of
      shock-like pain to the lower limbs. Results The patient underwent a successful
      cyst decompression. Conclusion A few cases have been reported in the literature.
      Including this case, there are a total of eight cases of ependymal cyst in the
      conocaudal segment reported. 

PMID- 25072005
TI  - Spinal epidural hematoma caused by pseudogout: a case report and literature
      review.
AB  - Study Design Case report. Objective We present the first reported case of
      spontaneous spinal epidural hematoma secondary to calcium pyrophosphate crystal
      deposition disease (pseudogout) in a 75-year-old woman. Methods A retrospective
      review of the patient's case notes was undertaken and the limited literature on
      this subject reviewed. Results This patient presented with sudden-onset lower
      limb paresis, sensory loss, urinary retention, and back pain. Magnetic resonance
      imaging showed an epidural hematoma, which was evacuated. Histologic specimens of
      the clot showed calcium pyrophosphate dihydrate crystal deposits (pseudogout).
      Conclusion The importance of histopathologic review of surgical specimens is
      highlighted when considering the differential diagnosis of apparently spontaneous
      spinal epidural hematoma. 

PMID- 25072006
TI  - The transpalatal approach to repair of congenital Basal skull base cephaloceles.
AB  - Basal skull base herniations, including meningoceles and encephaloceles, are rare
      and may present with characteristic facial and neurologic features. The
      traditional craniotomy approach has known morbidity, and nasal endoscopy may not
      allow for control of large posterior basal defects, especially in newborns. We
      present two cases of successful repair of basal transsphenoidal meningoceles
      using an oral-transpalatal approach. The first patient with an intact palate
      presented with respiratory distress, and a palatectomy was performed for access
      to the skull base. The second patient had a large basal herniation that was
      reduced through a congenital midline cleft palate, and a calvarial bone graft was
      used to repair the defect. A literature search revealed 10 previous successful
      cases using the transpalatal repair, which allows for excellent access, low
      morbidity, and a team-oriented method to skull base surgery. 

PMID- 25072007
TI  - Volumetry and analysis of anatomical variants of the anterior portion of the
      petrous apex outlined by the kawase triangle using computed tomography.
AB  - Background Anterior petrosectomy has become an increasingly used approach for
      petroclival lesions. This study measures the volume and the anatomical variants
      of the anterior portion of the petrous apex outlined by the Kawase triangle using
      computed tomography (CT). Methods This was a transversal retrospective study. We
      assessed the anterior petrous apex portion outlined by the Kawase triangle in
      consecutive patients > 18 years of age from CT scans of temporal bone stored in
      an archive system. The volumetry was performed on a workstation. Results A total
      of 154 petrosal apex were analyzed in 77 patients (36 men). The average volume of
      the region outlined by the Kawase triangle was 1.89 +/- 0.52 cm(3). The volume
      average in men was 2.01 +/- 0.58 cm(3), and the average in women was 1.79 +/-
      0.41 cm(3). Intra- and interobserver agreement were both excellent, and there was
      little variance. Nineteen petrous apex demonstrated anatomical variations. In 18
      cases it was pneumatized, and in one case a vascular or nerve-like structure was
      identified, a report we did not find in the literature. Conclusion The volumetry
      of the petrous apex anterior portion outlined by the Kawase triangle can be made
      by CT with excellent intra- and interobserver agreement and reproducibility.
      There are anatomical variants in this region that are relevant to surgery. 

PMID- 25072008
TI  - A review of stereotactic radiosurgery practice in the management of skull base
      meningiomas.
AB  - Gross total resection of skull base meningiomas poses a surgical challenge due to
      their proximity to neurovascular structures. Once the gold standard therapy for
      skull base meningiomas, microsurgery has been gradually replaced by or used in
      combination with stereotactic radiosurgery (SRS). This review surveys the safety
      and efficacy of SRS in the treatment of cranial base meningiomas including 36
      articles from 1991 to 2010. SRS produces excellent tumor control with low
      morbidity rates compared with surgery alone for asymptomatic small skull base
      meningiomas, patients with risk factors precluding conventional surgery, and as
      adjuvant therapy for recurrent or residual lesions. 

PMID- 25072009
TI  - Management of hypoglossal schwannomas: single institutional experience of 14
      cases.
AB  - Background Hypoglossal schwannomas are rare intracranial neoplasms. Microsurgical
      resection with the goal of cure is the aim of management but is associated with a
      high rate of postoperative morbidity. Objective The objective of the study was to
      outline the clinical presentation, radiologic characteristics, surgical
      techniques, postoperative morbidity, and long-term follow-up results for
      hypoglossal schwannomas. Methods Patients treated for hypoglossal schwannoma at
      the Department of Neurosurgery of a tertiary-level referral institution from
      January 2001 until December 2010 were analyzed retrospectively using hospital
      records. Results There were 14 patients who were treated in the study period.
      Tongue atrophy and swallowing difficulties were the most common presenting
      symptoms. Surgery done in 12 patients using a variety of approaches (retromastoid
      retrosigmoid suboccipital in 9, midline suboccipital in 2, and far lateral in 1).
      Five patients having small residual tumors received gamma knife (GK)
      subsequently. two patients received primary GK stereotactic radiosurgery. Three
      patients had permanent morbidity in the form of cranial nerve paresis. Immediate
      postoperative complications like cerebrospinal fluid leak and pneumonia were
      present in three patients. Conclusion Complete microsurgical resection is often
      associated with a high rate of morbidity. Subtotal and near-total resection
      followed by stereotactic radiosurgery or observation now offers an alternative
      approach. 

PMID- 25072010
TI  - Endoscopic transnasal surgery as a replacement for maxillotomy techniques to
      approach the central skull base: fewer complications and more acceptable to
      patients?
AB  - Objectives To compare the complication rates of endoscopic transnasal and open
      maxillotomy approaches for the central skull base. Design Retrospective review.
      Setting Single-center study, London, United Kingdom. Participants From 1992 to
      2012, 81 patients underwent surgery for skull base lesions, 59 by maxillotomy and
      22 by endoscopy. Main Outcome Measures Total time of surgical anesthesia, blood
      loss, complications, duration of tracheal intubation, duration of hospital stay,
      myelopathy score, and mortality rate. Results The surgical time, blood loss, and
      duration of the postoperative intubation period were significantly less with
      endoscopy (p < 0.001). Requirements for intensive care, ward stay, and total
      hospital stay were also significantly less in the endoscopic group (p = 0.01, p <
      0.001, and p < 0.001, respectively). The complication rate was lower with
      transnasal endoscopic surgery. Conclusion In patients for whom open maxillotomy
      or endoscopic surgery are both feasible, the preference should be to perform
      endoscopic surgery, with better visualization and fewer complications. 

PMID- 25072011
TI  - Minimally Invasive Technique for Repairing CSF Leaks Due to Defects of Posterior
      Table of Frontal Sinus.
AB  - Objective Cerebrospinal fluid (CSF) leaks from the frontoethmoid and sphenoid
      region can be easily dealt with endoscopic approaches, but CSF rhinorrhea due to
      frontal sinus fractures are difficult to treat solely by the nasal endoscopic
      approach and may require external repair. The technique described targets defects
      of the posterior table of the frontal sinus where conventional osteoplastic
      approach of obliteration is usually done. This technique is minimally invasive
      and involves repair using an endoscope via a frontal trephine. Methods We have
      treated five cases of traumatic CSF rhinorrhea with this technique, and the mean
      follow-up is 1 year (range: 10-14 months). The frontal sinus is opened by making
      a small stab incision (frontal trephine), and the defect site is localized by
      visualization via endoscope through the trephine. The repair is then performed
      with fat, bone graft, and fibrin glue. Results Closure of the defect was achieved
      in a single stage in all the patients, and none of them had a recurrence of leak
      in the 1-year follow-up period. Conclusion This is a good technique for
      superiorly and laterally placed posterior table defects of the frontal sinus with
      minimal morbidity and excellent closure rates. 

PMID- 25072012
TI  - Dual-Port 2D and 3D Endoscopy: Expanding the Limits of the Endonasal Approaches
      to Midline Skull Base Lesions with Lateral Extension.
AB  - Objective To investigate a novel dual-port endonasal and subtemporal endoscopic
      approach targeting midline lesions with lateral extension beyond the
      intracavernous carotid artery anteriorly and the Dorello canal posteriorly.
      Methods Ten dual-port approaches were performed on five cadaveric heads. All
      specimens underwent an endoscopic endonasal approach from the sella to middle
      clivus. The endonasal port was combined with an anterior or posterior endoscopic
      extradural subtemporal approach. The anterior subtemporal port was placed
      directly above the middle third of the zygomatic arch, and the posterior port was
      placed at its posterior root. The extradural space was explored using two
      dimensional and three-dimensional endoscopes. Results The anterior subtemporal
      port complemented the endonasal port with direct access to the Meckel cave,
      lateral sphenoid sinus, superior orbital fissure, and lateral and posterosuperior
      compartments of the cavernous sinus; the posterior subtemporal port enhanced
      access to the petrous apex. Endoscopic dissection and instrument maneuverability
      were feasible and performed without difficulty in both the anterior and posterior
      subtemporal ports. Conclusion The anterior and posterior subtemporal ports
      enhanced exposure and control of the region lateral to the carotid artery and
      Dorello canal. Dual-port neuroendoscopy is still minimally invasive yet
      dramatically increases surgical maneuverability while enhancing visualization and
      control of anatomical structures. 

PMID- 25072013
TI  - The significance of intraoperative electromyographic "lateral spread" in
      predicting outcome of microvascular decompression for hemifacial spasm.
AB  - OBJECTIVES: During microvascular decompression (MVD) of the facial nerve for
      hemifacial spasm (HFS), an abnormal muscle response can be recorded upon
      stimulation of the facial nerve, also known as the lateral spread response. This
      response may vanish after MVD and has been associated with a successful outcome.
      The purpose of this study was to determine if resolution of lateral spread
      correlated with the elimination of HFS in a single surgeon's experience. Design
      and SETTING:  (1) Retrospective analysis of 38 patients undergoing MVD with
      intraoperative electromyography for HFS. (2) Meta-analysis of studies from the
      literature. MAIN OUTCOME MEASURE: Presence or absence of HFS and any
      complications. RESULTS: Lateral spread response was seen in 36 patients; 20
      patients had full resolution. Of these, 15 patients became HFS free, and 5 five
      patients still had some degree of HFS. Sixteen patients had a persistent lateral
      spread response despite a technically successful MVD; 11 of these became spasm
      free, and 5 still suffered from some degree of facial twitching. Analyzing 16
      studies reporting a total of 1301 patients, a significant correlation (p <
      0.0001) between response cessation and resolution of HFS was found. CONCLUSION:
      The role of monitoring lateral spread response as a predictor for clinical
      outcome is limited.

PMID- 25072014
TI  - Diffusion-weighted imaging of skull lesions.
AB  - Diffusion-weighted imaging can increase the conspicuity of skull lesions and be
      applied toward noninvasive differentiation of malignant from benign lesions.
      Malignant skull lesions generally display lower diffusivity than benign lesions,
      although there are exceptions, and clinical parameters and conventional imaging
      modalities should also be considered in the evaluation of skull lesions.
      Nevertheless, in some instances diffusion-weighted imaging (DWI) can be used for
      problem solving when conventional imaging features are indeterminate, such as
      with skull base involvement by nasopharyngeal carcinoma versus osteomyelitis. In
      addition, DWI may be useful for monitoring treatment effects. The use of readout
      segmented technique, parallel imaging, multishot acquisition, turbo spin-echo
      DWI, diffusion tensor imaging, and higher field strengths can improve image
      quality. The feasibility of implementing DWI for characterizing skull lesions,
      the DWI findings of benign and malignant skull lesions, and technical
      considerations are discussed in this article. 

PMID- 25072015
TI  - Large Vestibular Schwannomas Presenting during Pregnancy: Management Strategies.
AB  - Objective Large vestibular schwannomas rarely present in pregnant women.
      Diagnosis and management of these tumors during pregnancy present a therapeutic
      challenge. Methods A 20-year-old primigravida woman at 26 weeks' gestation was
      transferred to our facility with gait imbalance, left facial weakness, left ear
      hearing loss, and recent nausea and vomiting. Magnetic resonance imaging revealed
      a large left cerebellopontine angle mass with extension into the left internal
      auditory canal and compression of the fourth ventricle resulting in mild
      hydrocephalus. The patient was admitted with a plan for early delivery at 32
      weeks followed by tumor resection. One week later, the patient's headache and
      neurologic symptoms worsened due to increased hydrocephalus; a
      ventriculoperitoneal shunt was placed. The next day, an emergent cesarean
      delivery was performed due to worsening respiratory status. Four days later, a
      tracheostomy and percutaneous endoscopic gastrostomy tube were placed due to
      dysphagia. Eight days after the delivery, the mass was resected with a left
      retrosigmoid approach without complications. Immunohistochemistry confirmed
      vestibular cellular schwannoma on cranial nerve VIII showing unusually high
      mitotic activity. Results The patient was discharged to inpatient rehabilitation
      on postoperative day 12 without new neurologic deficit. At 1 month, the patient
      was swallowing without aspiration. Her facial sensation had returned, her facial
      weakness remained stable, and her gait was significantly improved. Conclusion If
      the patient is neurologically stable, the best option is to delay resection until
      after delivery. If resection is necessary during pregnancy, the optimal time is
      during the second trimester. 

PMID- 25072017
TI  - Cancer spending and accountable care organizations: Evidence from the Physician
      Group Practice Demonstration.
AB  - BACKGROUND: Although accountable care organizations (ACOs) are rapidly being
      deployed in Medicare, little is known about how the model might affect high-risk,
      high cost groups such as cancer patients. The Physician Group Practice
      Demonstration, which ran from 2005 to 2010 in 10 physician groups, provides the
      best current evidence on the likely effectiveness of accountable care
      organizations for Medicare beneficiaries. Changes in cancer treatment and
      spending under this program may be indicative of cancer treatment under ACO
      payment reform. METHODS: Using Medicare fee-for-service claims data, regression
      analysis was used to estimate changes in payments for cancer patients using a
      difference-in-difference design comparing pre- (2001-2004) and post-intervention
      (2005-2009) trends in spending on cancer patients in PGPD participants to local
      control groups. RESULTS: Regression models indicate the Physician Group Practice
      Demonstration was associated with average Medicare spending reductions per cancer
      patient of $721 annually across participating sites, an annual 3.9% reduction in
      payments per patient. Savings derived entirely from reductions in acute care
      payments for inpatient stays. The Demonstration was also associated with a
      reduction in mortality among cancer patients. There was no significant change in
      the proportion of deaths occurring in the hospital. There were significant
      reductions in hospice use, hospital discharges and ICU days, but no reductions in
      cancer-specific procedures or chemotherapy. Estimates of all measures varied
      considerably across participating sites. CONCLUSIONS: The Physician Group
      Practice Demonstration was associated with reductions in admissions for inpatient
      care among beneficiaries with prevalent cancer, with no adverse effect on
      mortality. Participants in the Physician Group Practice Demonstration did not
      change the trajectory of spending for cancer-specific treatments. IMPLICATIONS:
      Inpatient care for beneficiaries with cancer may represent a significant source
      of potential savings for ACOs, but evidence from the Physician Group Practice
      Demonstration indicates that no changes were made to cancer treatments such as
      chemotherapy or surgical procedures.

PMID- 25072016
TI  - Autism Spectrum Disorder: Defining Dimensions and Subgroups.
AB  - Autism spectrum disorder (ASD) is a behaviorally defined neurodevelopmental
      disorder associated with the presence of social-communication deficits and
      restricted and repetitive behaviors. In the latest conceptualization of ASD,
      these two behavioral dimensions represent the core defining features of ASD,
      whereas associated dimensions, such as intellectual and language ability, provide
      a means for describing the ASD heterogeneity. In addition, the characterization
      of ASD subgroups, defined by the presence of known medical, genetic, or other
      psychiatric disorders, furthers our understanding of ASD heterogeneity. This
      paper reviews the history of autism, describes its core defining features, and
      provides an overview of the clinically and etiologically relevant subgroups that
      add to the complexity of this condition.

PMID- 25072018
TI  - Mitochondria regulate DNA damage and genomic instability induced by high LET
      radiation.
AB  - High linear energy transfer (LET) radiation including alpha particles and heavy
      ions is the major type of radiation find in space and is considered a potential
      health risk for astronauts. Even though the chance that these high LET particles
      traversing through the cytoplasm of cells is higher than that through the nuclei,
      the contribution of targeted cytoplasmic irradiation, to the induction of genomic
      instability and other chromosomal damages induced by high LET radiation is not
      known. In the present study, we investigated whether mitochondria are the
      potential cytoplasmic target of high LET radiation in mediating cellular damage
      using a mitochondrial DNA (mtDNA) depleted (rho0) human small airway epithelial
      (SAE) cell model and a precision charged particle microbeam with a beam width of
      merely one micron. Targeted cytoplasmic irradiation by high LET alpha particles
      induced DNA oxidative damage and double strand breaks in wild type rho+ SAE
      cells. Furthermore, there was a significant increase in autophagy, micronuclei,
      which is an indication of genomic instability, together with the activation of
      nuclear factor kappa-B (NF-kappaB) and mitochondrial inducible nitric oxide
      synthase (iNOS) signaling pathways in rho+ SAE cells. In contrast, rho0 SAE cells
      exhibited a significantly lower response to these same endpoints examined after
      cytoplasmic irradiation with high LET alpha particles. The results indicate that
      mitochondria are essential in mediating cytoplasmic radiation induced genotoxic
      damage in mammalian cells. Furthermore, the findings may shed some light in the
      design of countermeasures for space radiation.

PMID- 25072020
TI  - Concurrent radiotherapy with Carboplatin and cetuximab for the treatment of
      medically compromised patients with locoregionally advanced head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: Cetuximab (Cx) + radiation therapy (RT) is well-tolerated and has
      improved survival in patients (pts) with locoregionally advanced head and neck
      squamous cell carcinomas (LA-HNSCC). However, its efficacy when compared to HD
      DDP + RT has been questioned. At our institution, low-dose weekly carboplatin is
      added to Cx + RT for patients unsuitable for HD-DDP. METHODS: We reviewed records
      of 16 patients with LA-HNSCC treated with definitive Cx + carboplatin + RT at the
      University of Miami from 2007 to 2011. Median follow-up was 24 months (range: 1
      69 months). RESULTS: Median age: 71.5 years (range: 57-90 years); 15 male, 1
      female. ECOG PS 0 = 15, 1 = 1. TNM staging was: T 1 = 1, T 2 = 5, T 3 = 8, T 4 =
      2; N stage: N 0 = 8, N 1 = 5, N 2a = 2, N 2b = 1. All patients received weekly
      carboplatin (AUC 1.5-2), Cx given conventionally and daily conventionally
      fractionated RT. Median total weeks of concurrent systemic therapy = 7 (range: 3
      8 weeks). RT was delivered to a median total dose of 70 Gy (range 30-74 Gy). Of
      the 15 evaluable patients, there were: 12 CR, 2 PR, and 1 PD. There were three
      local in-field failures, two regional failures, and three distant failures. At
      last follow-up, 8/15 patients remained with NED. Three-year locoregional
      recurrence was 28.3% (95% CI: 7.7-53.9%). Mean percentage of weight loss was 14%
      (range: 6-26%). Two patients required systemic therapy dose reduction. Three
      patients experienced a treatment delay and three did not finish RT as planned
      including a patient who received only 30 Gy due to death secondary to MI during
      treatment. CONCLUSION: In this small retrospective series, carboplatin/Cx/RT was
      well-tolerated and efficacious in patients unsuitable for HD-DDP having LA-HNSCC.
      Acute toxicities were similar to Cx + RT, likely due to the non-overlapping
      toxicity profiles of the two systemic agents. We hypothesize that the addition of
      a well-tolerated cytotoxic chemotherapy agent may improve the therapeutic ratio
      of Cx + RT in patients who are poor candidates for more aggressive therapies and
      warrants evaluation in a prospective manner.

PMID- 25072019
TI  - Orchestration of angiogenesis by immune cells.
AB  - It is widely accepted that the tumor microenvironment (TUMIC) plays a major role
      in cancer and is indispensable for tumor progression. The TUMIC involves many
      "players" going well beyond the malignant-transformed cells, including stromal,
      immune, and endothelial cells (ECs). The non-malignant cells can acquire tumor
      promoting functions during carcinogenesis. In particular, these cells can
      "orchestrate" the "symphony" of the angiogenic switch, permitting the creation of
      new blood vessels that allows rapid expansion and progression toward malignancy.
      Considerable attention within the context of tumor angiogenesis should focus not
      only on the ECs, representing a fundamental unit, but also on immune cells and on
      the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically
      show a tumor-induced polarization associated with attenuation of anti-tumor
      functions and generation of pro-tumor activities, among these angiogenesis. Here,
      we propose a scenario suggesting that the angiogenic switch is an immune switch
      arising from the pro-angiogenic polarization of immune cells. This view links
      immunity, inflammation, and angiogenesis to tumor progression. Here, we review
      the data in the literature and seek to identify the "conductors" of this
      "orchestra." We also suggest that interrupting the immune -> inflammation ->
      angiogenesis -> tumor progression process can delay or prevent tumor insurgence
      and malignant disease. 

PMID- 25072021
TI  - New Approaches to Target T-ALL.
AB  - Acute lymphoblastic leukemia is the most common malignancy in children. Although
      it is now curable in 80-90% of cases, patients with T-cell acute lymphoblastic
      leukemia (T-ALL) experience a higher frequency of induction failure and early
      relapse. Despite aggressive treatment approaches, including transplantation and
      new salvage regimens, most children with relapsed T-ALL will not be cured. As
      such, we are in need of new targeted therapies for the disease. Recent advances
      in the molecular characterization of T-ALL have uncovered a number of new
      therapeutic targets. This review will summarize recent advancements in the study
      of inhibiting the NOTCH1, PI3K-AKT, and Cyclin D3:CDK4/6 pathways as therapeutic
      strategies for T-ALL. We will focus on pre-clinical studies supporting the
      testing of small-molecule inhibitors targeting these proteins and the rationale
      of combination therapies. Moreover, epigenetic approaches to modulate T-ALL are
      rapidly emerging. Here, we will discuss the data supporting the role of
      bromodomain and extra-terminal bromodomain inhibitors in human T-ALL. 

PMID- 25072023
TI  - The yin-yang of microvesicles (exosomes) in cancer biology.

PMID- 25072022
TI  - Inhibition of notch signaling in combination with Paclitaxel reduces platinum
      resistant ovarian tumor growth.
AB  - INTRODUCTION: Ovarian cancer (OvCa) is the most lethal gynecologic malignancy in
      the United States because of chemoresistant recurrent disease. Our objective was
      to investigate the efficacy of inhibiting the Notch pathway with a gamma
      secretase inhibitor (GSI) in an OvCa patient-derived xenograft model as a single
      agent therapy and in combination with standard chemotherapy. METHODS:
      Immunocompromised mice bearing xenografts derived from clinically platinum
      sensitive human ovarian serous carcinomas were treated with vehicle, GSI (MRK
      003) alone, paclitaxel and carboplatin (P/C) alone, or the combination of GSI and
      P/C. Mice bearing platinum-resistant xenografts were given GSI with or without
      paclitaxel. Gene transcript levels of the Notch pathway target Hes1 were analyzed
      using RT-PCR. Notch1 and Notch3 protein levels were evaluated. The Wilcoxon rank
      sum test was used to assess significance between the different treatment groups.
      RESULTS: Expression of Notch1 and 3 was variable. GSI alone decreased tumor
      growth in two of three platinum-sensitive ovarian tumors (p < 0.05), as well as
      in one of three platinum-sensitive tumors (p = 0.04). The combination of GSI and
      paclitaxel was significantly more effective than GSI alone and paclitaxel alone
      in all platinum-resistant ovarian tumors (all p < 0.05). The addition of GSI did
      not alter the effect of P/C in platinum-sensitive tumors. Interestingly, although
      the response of each tumor to chronic GSI exposure did not correlate with its
      endogenous level of Notch expression, GSI did negatively affect Notch signaling
      in an acute setting. CONCLUSION: Inhibiting the Notch signaling cascade with a
      GSI reduces primary human xenograft growth in vivo. GSI synergized with
      conventional cytotoxic chemotherapy only in the platinum-resistant OvCa models
      with single agent paclitaxel. These findings suggest inhibition of the Notch
      pathway in concert with taxane therapy may hold promise for treatment of platinum
      resistant OvCa.

PMID- 25072024
TI  - Is the Evaluation of Quality of Life in NSCLC Trials Important? Are the Results
      to be Trusted?
AB  - The majority of patients with non-small cell lung cancer present at the time of
      diagnosis with stage IV metastatic disease and they experience 2 or more disease
      related symptoms. These symptoms may have a negative impact on their health
      related quality of life (HR QOL). Data has shown many of these patients prefer a
      therapy to improve their symptoms rather than receive a therapy which slightly
      prolongs their survival without improving their symptoms. The improvement of
      disease-related symptoms on a specific drug or regimen augments the significance
      of prolongation of the progression-free survival or the response rate as well as
      symptom worsening. The choice of the questionnaires to evaluate patients'
      reported outcomes and HR QOL benefits and the methods of collecting the data and
      their interpretations are very important. Only if the data are collected and
      analyzed properly will they be meaningful and can then be viewed as components
      that add the total value to a treatment and provide a comprehensive picture of
      the benefits and risks of a certain anticancer therapy. 

PMID- 25072026
TI  - The treatment of metastatic non-small cell lung cancer in the elderly: an
      evidence-based approach.
AB  - An increasing proportion of patients with advanced non-small cell lung cancer
      (NSCLC) are over 70 years old, raising unique challenges for treatment decision
      making. While these patients are underrepresented in clinical trials, there is an
      emerging body of evidence associated with this group. The lesson of comprehensive
      geriatric assessment is that chronological age does not always correlate with
      physiological age and a variety of important co-morbidities and geriatric
      syndromes can go undetected in a typical history and physical. These co
      morbidities and expected physiologic changes due to aging complicate decision
      making around appropriate treatment. This review discusses geriatric assessment
      in elderly cancer patients and evaluates the current evidence for chemotherapy
      and targeted therapy for patients with advanced NSCLC aged >=70 years. 

PMID- 25072025
TI  - Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast
      Cancer Progression.
AB  - Epidemiologic studies demonstrate that obesity is associated with an aggressive
      subtype of breast cancer called basal-like breast cancer (BBC). Using the C3(1)
      TAg murine model of BBC, we previously demonstrated that mice displayed an early
      onset of tumors when fed obesogenic diets in the adult window of susceptibility.
      Obesity was also shown to elevate mammary gland expression and activation of
      hepatocyte growth factor (HGF)/c-Met compared to lean controls, a pro-tumorigenic
      pathway associated with BBC in patients. Epidemiologic studies estimate that
      weight loss could prevent a large proportion of BBC. We sought to investigate
      whether weight loss in adulthood prior to tumor onset would protect mice from
      accelerated tumorigenesis observed in obese mice. Using a life-long model of
      obesity, C3(1)-TAg mice were weaned onto and maintained on an obesogenic high-fat
      diet. Obese mice displayed significant elevations in tumor progression, but not
      latency or burden. Tumor progression was significantly reversed when obese mice
      were induced to lose weight by switching to a control low-fat diet prior to tumor
      onset compared to mice maintained on obesogenic diet. We investigated the HGF/c
      Met pathway known to regulate tumorigenesis. Importantly, HGF/c-Met expression in
      normal mammary glands and c-Met in tumors was elevated with obesity and was
      significantly reversed with weight loss. Changes in tumor growth could not be
      explained by measures of HGF action including phospho-AKT or phospho-S6. Other
      mediators associated with oncogenesis such as hyperinsulinemia and a high
      leptin:adiponectin ratio were elevated by obesity and reduced with weight loss.
      In sum, weight loss significantly blunted the obesity-responsive pro-tumorigenic
      HGF/c-Met pathway and improved several metabolic risk factors associated with
      BBC, which together may have contributed to the dramatic reversal of obesity
      driven tumor progression. Future research aims to evaluate the role of obesity
      and the HGF/c-Met pathway in basal-like breast cancer progression. 

PMID- 25072027
TI  - Cancer wars: significance of protein unfolding in cancer and its inhibition with
      natural amphiphilic substances.

PMID- 25072028
TI  - Infections Caused by Acinetobacter baumannii in Recipients of Hematopoietic Stem
      Cell Transplantation.
AB  - Acinetobacter baumannii (A. baumannii) is a Gram-negative, strictly aerobic, non
      fermentative coccobacillus, which is widely distributed in nature. Recently, it
      has emerged as a major cause of health care-associated infections (HCAIs) in
      addition to its capacity to cause community-acquired infections. Risk factors for
      A. baumannii infections and bacteremia in recipients of hematopoietic stem cell
      transplantation include: severe underlying illness such as hematological
      malignancy, prolonged use of broad-spectrum antibiotics, invasive instrumentation
      such as central venous catheters or endotracheal intubation, colonization of
      respiratory, gastrointestinal, or urinary tracts in addition to severe
      immunosuppression caused by using corticosteroids for treating graft versus host
      disease. The organism causes a wide spectrum of clinical manifestations, but
      serious complications such as bacteremia, septic shock, ventilator-associated
      pneumonia, extensive soft tissue necrosis, and rapidly progressive systemic
      infections that ultimately lead to multi-organ failure and death are prone to
      occur in severely immunocompromised hosts. The organism is usually resistant to
      many antimicrobials including penicillins, cephalosporins, trimethoprim
      sulfamethoxazole, almost all fluoroquinolones, and most of the aminoglycosides.
      The recently increasing resistance to carbapenems, colistin, and polymyxins is
      alarming. Additionally, there are geographic variations in the resistance
      patterns and several globally and regionally resistant strains have already been
      described. Successful management of A. baumannii infections depends upon
      appropriate utilization of antibiotics and strict application of preventive and
      infection control measures. In uncomplicated infections, the use of a single
      active beta-lactam may be justified, while definitive treatment of complicated
      infections in critically ill individuals may require drug combinations such as
      colistin and rifampicin or colistin and carbapenem. Mortality rates in patients
      having bacteremia or septic shock may reach 70%. Good prognosis is associated
      with presence of local infection, absence of multidrug resistant strain, and
      presence of uncomplicated infection while poor outcome is associated with severe
      underlying medical illness, bacteremia, septic shock, multi-organ failure, HCAIs,
      admission to intensive care facilities for higher levels of care, and culture of
      certain aggressive genotypes of A. baumannii. 

PMID- 25072029
TI  - Understanding Anaplasmataceae pathogenesis using "Omics" approaches.
AB  - This paper examines how "Omics" approaches improve our understanding of
      Anaplasmataceae pathogenesis, through a global and integrative strategy to
      identify genes and proteins involved in biochemical pathways key for pathogen
      host-vector interactions. The Anaplasmataceae family comprises obligate
      intracellular bacteria mainly transmitted by arthropods. These bacteria are
      responsible for major human and animal endemic and emerging infectious diseases
      with important economic and public health impacts. In order to improve disease
      control strategies, it is essential to better understand their pathogenesis. Our
      work focused on four Anaplasmataceae, which cause important animal, human and
      zoonotic diseases: Anaplasma marginale, A. phagocytophilum, Ehrlichia
      chaffeensis, and E. ruminantium. Wolbachia spp. an endosymbiont of arthropods was
      also included in this review as a model of a non-pathogenic Anaplasmataceae. A
      gap analysis on "Omics" approaches on Anaplasmataceae was performed, which
      highlighted a lack of studies on the genes and proteins involved in the infection
      of hosts and vectors. Furthermore, most of the studies have been done on the
      pathogen itself, mainly on infectious free-living forms and rarely on
      intracellular forms. In order to perform a transcriptomic analysis of the
      intracellular stage of development, researchers developed methods to enrich
      bacterial transcripts from infected cells. These methods are described in this
      paper. Bacterial genes encoding outer membrane proteins, post-translational
      modifications, eukaryotic repeated motif proteins, proteins involved in osmotic
      and oxidative stress and hypothetical proteins have been identified to play a key
      role in Anaplasmataceae pathogenesis. Further investigations on the function of
      these outer membrane proteins and hypothetical proteins will be essential to
      confirm their role in the pathogenesis. Our work underlines the need for further
      studies in this domain and on host and vector responses to infection. 

PMID- 25072030
TI  - Screening of Mycobacterium avium subsp. paratuberculosis mutants for attenuation
      in a bovine monocyte-derived macrophage model.
AB  - Vaccination remains a major tool for prevention and progression of Johne's
      disease, a chronic enteritis of ruminants worldwide. Currently there is only one
      licensed vaccine within the United States and two vaccines licensed
      internationally against Johne's disease. All licensed vaccines reduce fecal
      shedding of Mycobacterium avium subsp. paratuberculosis (MAP) and delay disease
      progression. However, there are no available vaccines that prevent disease onset.
      A joint effort by the Johne's Disease Integrated Program (JDIP), a USDA-funded
      consortium, and USDA-APHIS/VS sought to identify transposon insertion mutant
      strains as vaccine candidates in part of a three phase study. The focus of the
      Phase I study was to evaluate MAP mutant attenuation in a well-defined in vitro
      bovine monocyte-derived macrophage (MDM) model. Attenuation was determined by
      colony forming unit (CFUs) counts and slope estimates. Based on CFU counts alone,
      the MDM model did not identify any mutant that significantly differed from the
      wild-type control, MAP K-10. Slope estimates using mixed models approach
      identified six mutants as being attenuated. These were enrolled in protection
      studies involving murine and baby goat vaccination-challenge models. MDM based
      approach identified trends in attenuation but this did not correlate with
      protection in a natural host model. These results suggest the need for
      alternative strategies for Johne's disease vaccine candidate screening and
      evaluation. 

PMID- 25072032
TI  - Shiga toxin-producing Escherichia coli in human, cattle, and foods. Strategies
      for detection and control.

PMID- 25072031
TI  - Evaluation of eight live attenuated vaccine candidates for protection against
      challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice.
AB  - Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP),
      which results in serious economic losses worldwide in farmed livestock such as
      cattle, sheep, and goats. To control this disease, an effective vaccine with
      minimal adverse effects is needed. In order to identify a live vaccine for
      Johne's disease, we evaluated eight attenuated mutant strains of MAP using a
      C57BL/6 mouse model. The persistence of the vaccine candidates was measured at 6,
      12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both
      the liver and spleens up until the 12-week time point. The remaining five mutants
      showed no survival in those tissues, indicating their complete attenuation in the
      mouse model. The candidate vaccine strains demonstrated different levels of
      protection based on colonization of the challenge strain in liver and spleen
      tissues at 12 and 18 weeks post vaccination. Based on total MAP burden in both
      tissues at both time points, strain 315 (MAP1566::Tn5370) was the most protective
      whereas strain 318 (intergenic Tn5367 insertion between MAP0282c and MAP0283c)
      had the most colonization. Mice vaccinated with an undiluted commercial vaccine
      preparation displayed the highest bacterial burden as well as enlarged spleens
      indicative of a strong infection. Selected vaccine strains that showed promise in
      the mouse model were moved forward into a goat challenge model. The results
      suggest that the mouse trial, as conducted, may have a relatively poor predictive
      value for protection in a ruminant host such as goats. 

PMID- 25072033
TI  - Modeling the growth of Listeria monocytogenes on the surface of smear- or mold
      ripened cheese.
AB  - Surface-ripened cheeses are matured by means of manual or mechanical technologies
      posing a risk of cross-contamination, if any cheeses are contaminated with
      Listeria monocytogenes. In predictive microbiology, primary models are used to
      describe microbial responses, such as growth rate over time and secondary models
      explain how those responses change with environmental factors. In this way,
      primary models were used to assess the growth rate of L. monocytogenes during
      ripening of the cheeses and the secondary models to test how much the growth rate
      was affected by either the pH and/or the water activity (aw) of the cheeses. The
      two models combined can be used to predict outcomes. The purpose of these
      experiments was to test three primary (the modified Gompertz equation, the
      Baranyi and Roberts model, and the Logistic model) and three secondary (the
      Cardinal model, the Ratowski model, and the Presser model) mathematical models in
      order to define which combination of models would best predict the growth of L.
      monocytogenes on the surface of artificially contaminated surface-ripened
      cheeses. Growth on the surface of the cheese was assessed and modeled. The
      primary models were firstly fitted to the data and the effects of pH and aw on
      the growth rate (MUmax) were incorporated and assessed one by one with the
      secondary models. The Logistic primary model by itself did not show a better fit
      of the data among the other primary models tested, but the inclusion of the
      Cardinal secondary model improved the final fit. The aw was not related to the
      growth of Listeria. This study suggests that surface-ripened cheese should be
      separately regulated within EU microbiological food legislation and results
      expressed as counts per surface area rather than per gram. 

PMID- 25072034
TI  - Mel - personal reminiscence.

PMID- 25072035
TI  - The new concept of univentricular heart.
AB  - The concept of univentricular heart moved from hearts with only one ventricle
      connected with atria [double inlet ventricle or absent atrioventricular (AV)
      connection] to hearts not amenable to biventricular repair, namely hearts with
      two ventricles unable to sustain separately pulmonary and systemic circulations
      in sequence. In the latter definition, even hearts with one hypoplastic ventricle
      are considered "functional" univentricular hearts. They include pulmonary/aortic
      atresia or severe stenosis with hypoplastic ventricle, and rare conditions like
      huge intramural cardiac tumors and Ebstein anomaly with extreme atrialization of
      right ventricular cavity. In this setting, the surgical repair is univentricular
      with "Fontan" operation, bypassing the ventricular mass. In other words,
      functionally univentricular heart is a condition in which, after surgery, only
      one ventricle sustain systemic circulation. Univentricular hearts (double inlet
      or absent AV connection) almost invariably show two ventricular chambers, one
      main and one accessory, which lacks an inlet portion. The latter is located
      posteriorly when morphologically left and anteriorly when morphologically right.
      As far as double inlet left ventricle, this is usually associated with discordant
      ventriculo-arterial (VA) connection (transposition of the great arteries) and all
      the blood flow to the aorta, which takes origin from the hypoplastic anterior
      right ventricle, is ventricular septal defect (bulbo-ventricular foramen)
      dependent. If restrictive, an aortic arch obstruction may be present. Double
      inlet left ventricle may be rarely associated with VA concordance (Holmes heart).
      As far as double inlet right ventricle with posterior hypoplastic left
      ventricular cavity, ventriculo-arterial connection is usually of double outlet
      type; thus the term double inlet-outlet right ventricle may be coined. Absent
      right or left AV connection may develop in the setting of both d- or l-loop,
      whatever the situs. In this condition, the contra-lateral patent AV valve may be
      either mitral or tricuspid in terms of morphology and the underlying ventricle
      (main chamber) either morphologically left or right. Establishing the loop,
      whatever right or left (also called right or left ventricular topology), is a
      fundamental step in the segmental-sequential analysis of congenital heart
      disease. 

PMID- 25072036
TI  - Urinary Continence Following Repair of Intermediate and High Urogenital Sinus
      (UGS) in CAH. Experience with 55 Cases.
AB  - AIM: To evaluate postoperative urinary continence in patients with congenital
      adrenal hyperplasia (CAH) with intermediate (IT) and high urogenital sinus (UGS)
      who underwent a UGS mobilization maneuver. METHODS: We called IT to those that
      although needing an aggressive dissection to get to the vagina, still have enough
      urethra proximal to the vaginal confluence. Very low variants are excluded from
      this analysis. Dissection always started in the posterior wall of the UGS with an
      aggressive separation from the anterior rectal wall. If the wide portion of the
      vagina was reached dissection stopped and the UGS opened ventrally widening to
      the introitus. Nineteen patients were treated using this maneuver (Group 1). When
      more dissection was required the anterior wall of the UGS was dissected and
      carefully freed from the low retropubic space. Then the UGS was opened either
      ventrally or dorsally. Thirty three patients required this approach (Group 2).
      Combined procedures were used in three patients with high UGS (Group 3). RESULTS:
      Mean age at the time of the repair and length of the UGS were 12.2 years (4
      months-18 years) and 3.75 cm (3-8 cm) for G1; 8 years (5 months-17 years) and
      6.34 cm (4-12 cm) in G2 and 8.3 years (2-14 years) and 11.5 cm (11-12 cm) in G3.
      All patients had been regularly followed. Mean age at last follow up was 14.3,
      17, and 9.9 years for Groups 1, 2, and 3, respectively. All patients continue to
      void normally and are continent. All patients have two separate visible orifices
      in the vulva. Only three are sexually active. CONCLUSION: Urogenital sinus
      mobilization for vaginoplasty in girls with CAH does not compromise voiding
      function or urinary continence.

PMID- 25072037
TI  - Potential therapeutic use of the ketogenic diet in autism spectrum disorders.
AB  - The ketogenic diet (KGD) has been recognized as an effective treatment for
      individuals with glucose transporter 1 (GLUT1) and pyruvate dehydrogenase (PDH)
      deficiencies as well as with epilepsy. More recently, its use has been advocated
      in a number of neurological disorders prompting a newfound interest in its
      possible therapeutic use in autism spectrum disorders (ASD). One study and one
      case report indicated that children with ASD treated with a KGD showed decreased
      seizure frequencies and exhibited behavioral improvements (i.e., improved
      learning abilities and social skills). The KGD could benefit individuals with ASD
      affected with epileptic episodes as well as those with either PDH or mild
      respiratory chain (RC) complex deficiencies. Given that the mechanism of action
      of the KGD is not fully understood, caution should be exercised in ASD cases
      lacking a careful biochemical and metabolic characterization to avoid deleterious
      side effects or refractory outcomes. 

PMID- 25072039
TI  - Serotonin Transporter Genotype Linked to Adolescent Substance Use Treatment
      Outcome through Externalizing Behavior.
AB  - Meta-analyses suggest that the serotonin transporter linked polymorphic region (5
      HTTLPR) short (S) allele, relative to the long (L) allele, is associated with
      risk for alcohol dependence, particularly among individuals with early onset
      antisocial alcoholism. Youth in substance use treatment tend to show antisocial
      or externalizing behaviors, such as conduct problems, which predict worse
      treatment outcome. This study examined a pathway in which 5-HTTLPR genotype is
      associated with externalizing behavior, and the intermediate phenotype of
      externalizing behavior serves as a link between 5-HTTLPR genotype and substance
      use treatment outcome in youth. Adolescents (n = 142) who were recruited from
      addictions treatment were genotyped for 5-HTTLPR polymorphisms (S and LG carriers
      vs. LALA), assessed for externalizing and internalizing behaviors shortly after
      starting treatment, and followed over 6-months. 5-HTTLPR genotype was not
      associated with internalizing behaviors, and was not directly associated with 6
      month substance use outcomes. However, 5-HTTLPR genotype was associated with
      externalizing behaviors (S and LG > LALA), and externalizing behaviors predicted
      alcohol and marijuana problem severity at 6-month follow-up. Results indicated an
      indirect (p < 0.05) and non-specific (i.e., both alcohol and marijuana severity)
      effect of 5-HTTLPR genotype on youth substance use treatment outcomes, with
      externalizing behaviors as an important linking factor. Adolescents in substance
      use treatment with low expressing (S and LG) 5-HTTLPR alleles and externalizing
      behavior might benefit from intervention that addresses serotonergic functioning,
      externalizing behaviors, and substance use to improve outcomes. 

PMID- 25072038
TI  - GABAergic signaling as therapeutic target for autism spectrum disorders.
AB  - gamma-Aminobutyric acid (GABA), the main inhibitory neurotransmitter in the adult
      brain, early in postnatal life exerts a depolarizing and excitatory action. This
      depends on accumulation of chloride inside the cell via the cation-chloride
      importer NKCC1, being the expression of the chloride exporter KCC2 very low at
      birth. The developmentally regulated expression of KCC2 results in extrusion of
      chloride with age and a shift of GABA from the depolarizing to the
      hyperpolarizing direction. The depolarizing action of GABA leads to intracellular
      calcium rise through voltage-dependent calcium channels and/or N-methyl-d
      aspartate receptors. GABA-mediated calcium signals regulate a variety of
      developmental processes from cell proliferation migration, differentiation,
      synapse maturation, and neuronal wiring. Therefore, it is not surprising that
      some forms of neuro-developmental disorders such as autism spectrum disorders
      (ASDs) are associated with alterations of GABAergic signaling and impairment of
      the excitatory/inhibitory balance in selective neuronal circuits. In this review,
      we will discuss how changes of GABAA-mediated neurotransmission affect several
      forms of ASDs including the Fragile X, the Angelman, and Rett syndromes. Then, we
      will describe various animal models of ASDs with GABAergic dysfunctions,
      highlighting their behavioral deficits and the possibility to rescue them by
      targeting selective components of the GABAergic synapse. In particular, we will
      discuss how in some cases, reverting the polarity of GABA responses from the
      depolarizing to the hyperpolarizing direction with the diuretic bumetanide, a
      selective blocker of NKCC1, may have beneficial effects on ASDs, thus opening new
      therapeutic perspectives for the treatment of these devastating disorders. 

PMID- 25072040
TI  - Bovine Brain: An in vitro Translational Model in Developmental Neuroscience and
      Neurodegenerative Research.
AB  - Animal models provide convenient and clinically relevant tools in the research on
      neurodegenerative diseases. Studies on developmental disorders extensively rely
      on the use of laboratory rodents. The present mini-review proposes an alternative
      translational model based on the use of fetal bovine brain tissue. The bovine
      (Bos taurus) possesses a large and highly gyrencephalic brain and the long
      gestation period (41 weeks) is comparable to human pregnancy (38-40 weeks).
      Primary cultures obtained from fetal bovine brain constitute a validated in vitro
      model that allows examinations of neurons and/or glial cells under controlled and
      reproducible conditions. Physiological processes can be also studied on cultured
      bovine neural cells incubated with specific substrates or by electrically coupled
      electrolyte-oxide-semiconductor capacitors that permit direct recording from
      neuronal cells. Bovine neural cells and specific in vitro cell culture could be
      an alternative in comparative neuroscience and in neurodegenerative research,
      useful for studying development of normal and altered circuitry in a long
      gestation mammalian species. Use of bovine tissues would promote a substantial
      reduction in the use of laboratory animals. 

PMID- 25072041
TI  - Perceived Impacts of a Public Health Training Center Field Placement Program
      among Trainees: Findings from a Small Group Externship Experience.
AB  - There is heightened interest in identifying the impact of the federally funded
      Public Health Training Center (PHTC) program. Although evaluation studies have
      been conducted of public health training in general, evaluations of PHTC programs
      are rare. Field placement components are congressionally mandated requirements of
      PHTCs. Field placements are typically intensive, supervised externships for
      students to gain public health experience with local health departments or non
      profit organizations. We have found no published evaluations of PHTC field
      placement components. This may be because of their small size and unique nature.
      We designed and evaluated a 200-h field placement program at an established PHTC.
      The evaluation included pre/post surveys measuring public health core
      competencies, and post-experience interviews. We found significant increases in
      three competency domains among trainees: policy development and program planning,
      communication skills, and community dimensions of practice. These outcomes
      contribute to evidence based on the efficacy of PHTC field placement programs,
      and underscore their role in public health training. 

PMID- 25072042
TI  - Health, lifestyle, and gender influences on aging well: an Australian
      longitudinal analysis to guide health promotion.
AB  - A primary societal goal for aging is enabling older people to continue to live
      well as long as possible. The evidence base around aging well ("healthy,"
      "active," and "successful" aging) has been constructed mainly from academic and
      professional conceptualizations of mortality, morbidity, functioning, and
      psychological well-being with some attention to lay views. Our study aims to
      inform action on health promotion to achieve aging well as conceptualized by
      qualitative research identifying what older Australians themselves value most:
      continuing to live as long as possible in the community with independence in
      daily living, and good self-rated health and psychological well-being.
      Multivariate survival analyses from the Melbourne longitudinal studies on healthy
      aging program found that important threats to aging well for the total sample
      over a 12-year period were chronological age, multi-morbidity, low perceived
      social support, low nutritional score, and being under-weight. For men, threats
      to aging well were low strain, perceived inadequacy of social activity, and being
      a current smoker. For women, urinary incontinence, low physical activity and
      being under-weight were threats to aging well. The findings indicate that healthy
      lifestyles can assist aging well, and suggest the value of taking gender into
      account in health promotion strategies. 

PMID- 25072043
TI  - Khat Use, PTSD and Psychotic Symptoms among Somali Refugees in Nairobi - A Pilot
      Study.
AB  - In East-African and Arab countries, khat leaves are traditionally chewed in
      social settings. They contain the amphetamine-like alkaloid cathinone. Especially
      among Somali refugees, khat use has been associated with psychiatric symptoms. We
      assessed khat-use patterns and psychiatric symptoms among male Somali refugees
      living in a disadvantaged urban settlement area in Kenya, a large group that has
      not yet received scientific attention. We wanted to explore consume patterns and
      study the associations between khat use, traumatic experiences, and psychotic
      symptoms. Using privileged access sampling, we recruited 33 healthy male khat
      chewers and 15 comparable non-chewers. Based on extensive preparatory work, we
      assessed khat use, khat dependence according to DSM-IV, traumatic experiences,
      posttraumatic stress disorder (PTSD), and psychotic symptoms using standardized
      diagnostic instruments that had been adapted to the Somali language and culture.
      Hazardous use patterns like chewing for more than 24 h without interruption were
      frequently reported. All khat users fulfilled the DSM-IV-criteria for dependence
      and 85% reported functional khat use, i.e., that khat helps them to forget
      painful experiences. We found that the studied group was heavily burdened by
      traumatic events and posttraumatic symptoms. Khat users had experienced more
      traumatic events and had more often PTSD than non-users. Most khat users
      experience khat-related psychotic symptoms and in a quarter of them we found true
      psychotic symptoms. In contrast, among control group members no psychotic
      symptoms could be detected. We found first evidence for the existence and high
      prevalence of severely hazardous use patterns, comorbid psychiatric symptoms, and
      khat use as a self-medication of trauma-consequences among male Somali refugees
      in urban Kenyan refugee settlements. There is a high burden by psychopathology
      and adequate community-based interventions urgently need to be developed. 

PMID- 25072044
TI  - Knowledge, Practices, and Restrictions Related to Menstruation among Young Women
      from Low Socioeconomic Community in Mumbai, India.
AB  - The main objective was to assess knowledge, practices, and restrictions faced by
      young women regarding their menstrual hygiene. The views of adult women having
      young daughters were also included and both views were compared. In addition, the
      factors influencing the menstrual hygiene practices were also studied. The study
      was carried out during 2008 in Mumbai, India. The mixed methods approach was
      followed for the data collection. Both qualitative and quantitative methods were
      used to collect the data. For quantitative survey, totally 192 respondents (96
      adult and 96 younger women) were selected. While young women were asked about
      questions related to their menstruation, adult women were asked questions to find
      out how much they know about menstrual history of their daughters. The
      qualitative data helped to supplement the findings from the quantitative survey
      and to study the factors affecting menstrual practices in young women. The mean
      age at menarche reported was 13.4 years and 30-40% of young girls did not receive
      any information about menstruation before menarche. It is thus seen that very few
      young girls between the age group 15 and 24 years did receive any information
      before the onset of menstruation. Among those who received some information, it
      was not adequate enough. The source of information was also not authentic. Both
      young and adult women agreed on this. Due to the inadequate knowledge, there were
      certain unhygienic practices followed by the young girls resulting in poor
      menstrual hygiene. It also leads to many unnecessary restrictions on young girls
      and they faced many health problems and complaints, which were either ignored or
      managed inappropriately. The role of health sector was almost negligible from
      giving information to the management of health problems of these young girls.
      This paper reemphasizes the important, urgent, and neglected need of providing
      correct knowledge to the community including adolescent girls. 

PMID- 25072046
TI  - Ultrastructural study on tissue alterations caused by trypanosomatids in
      experimental murine infections.
AB  - The ultrastructural study in different tissues of mice experimentally infected
      with isolates of Trypanosoma evansi, Trypanosoma cruzi, and Leishmania mexicana
      reveals changes in cardiac myocytes, skeletal muscle fibers, and hepatic,
      adrenal, kidney, and spleen cells. Some of these changes were cytoarchitectural
      and others consisted of necrosis. Alterations in the microvasculature were also
      found. The mononuclear cell infiltrate included neutrophils, eosinophils, and
      macrophages. This work shows that diverse mice tissues are important target for
      trypanosomatids. 

PMID- 25072047
TI  - Primary care: mental and behavioral health and persons with intellectual and
      developmental disabilities.
AB  - INTRODUCTION: There are multiple ways to address the mental and behavioral health
      needs of people with intellectual and developmental disabilities (IDD). METHOD:
      In this paper, we do not argue for a particular approach or set of approaches,
      but instead review the benefits of integrating mental and behavioral health
      supports with primary healthcare based primarily on our experience in and
      understanding of healthcare systems in the United States. It is estimated that
      between 35 and 40% of people with IDD also live with psychiatric disorders. NADD,
      an association for persons with developmental disabilities and mental health
      needs in the US holds that coexisting IDD and a psychiatric disorder interferes
      with a person's education and job readiness, and disrupts family and peer
      relationships. Historically, the presence of such disorders among people with IDD
      was not well understood or was discounted altogether. CONCLUSION: Over the past
      15 years, however, greater attention is being paid to these comorbidities and
      their treatment, including the need to integrate mental and behavioral health
      treatments into primary care. Healthcare must account for multiple domains of
      quality of life, going beyond yearly physicals, and acute care visits, for
      example, to assess individuals' healthcare goals and support them in achieving
      those goals. While integrated healthcare delivery systems can be difficult to
      find and access for people with IDD, such approaches are more responsive to the
      comprehensive needs and desires of people with IDD.

PMID- 25072045
TI  - Tick-borne pathogen - reversed and conventional discovery of disease.
AB  - Molecular methods have increased the number of known microorganisms associated
      with ticks significantly. Some of these newly identified microorganisms are
      readily linked to human disease while others are yet unknown to cause human
      disease. The face of tick-borne disease discovery has changed with more diseases
      now being discovered in a "reversed way," detecting disease cases only years
      after the tick-borne microorganism was first discovered. Compared to the
      conventional discovery of infectious diseases, reverse order discovery presents
      researchers with new challenges. Estimating public health risks of such agents is
      especially challenging, as case definitions and diagnostic procedures may
      initially be missing. We discuss the advantages and shortcomings of molecular
      methods, serology, and epidemiological studies that might be used to study some
      fundamental questions regarding newly identified tick-borne diseases. With
      increased tick-exposure and improved detection methods, more tick-borne
      microorganisms will be added to the list of pathogens causing disease in humans
      in the future. 

PMID- 25072048
TI  - Taking stock of security concerns related to synthetic biology in an age of
      responsible innovation.

PMID- 25072049
TI  - Comorbidity of infectious diseases and anxiety disorders in adults and its
      association with quality of life: a community study.
AB  - OBJECTIVE: Infectious diseases and anxiety disorders are common and both are
      associated with substantial burden to individual, families, and society. A better
      understanding of their association may be helpful in explicating possible
      etiological mechanisms related to both. The goal of the current study was to
      investigate the relationship between specific infectious diseases and anxiety
      disorders among adults in the community, and to examine whether the co-occurrence
      of the two is associated with poorer quality of life compared to subjects with
      one or neither condition. METHODS: We used data from the 1998 German Mental
      Health survey with 4181 subjects aged 18-65. Various infectious diseases
      (lifetime) and health-related quality of life were assessed via self-report
      questionnaires and anxiety disorders (past 12-months) were diagnosed using M-CIDI
      interviews. Logistic regression analyses were used to evaluate the association
      between infectious diseases and anxiety disorders; a linear model adjusted for
      sex was used to examine whether comorbidity of infectious diseases and anxiety
      disorders was associated with quality of life. RESULTS: Whooping cough [odds
      ratio (OR) = 1.69, 95% confidence intervals (CI) = 1.36-2.09], scarlet fever (OR
      = 1.31, 95% CI = 1.02-1.68), and diphtheria (OR = 1.79, 95% CI = 1.21-2.64) were
      associated with increased prevalence of any anxiety disorder. Subjects with both
      infectious diseases and anxiety disorders reported lower levels of both mental
      and physical quality of life, compared with subjects with only one or neither
      condition. CONCLUSION: Extending prior research, this study suggests a
      relationship between specific infectious diseases and anxiety disorders in an
      adult community sample. Research targeting etiological mechanisms related to the
      interplay between infectious diseases and anxiety disorders is warranted.

PMID- 25072050
TI  - National-level biosafety norms needed for dual-use research.

PMID- 25072051
TI  - Frontiers in chemistry grand challenge: open communication to the world.

PMID- 25072052
TI  - Sensitive impedimetric biosensor for direct detection of diazinon based on
      lipases.
AB  - Two novel impedimetric biosensors for highly sensitive and rapid quantitative
      detection of diazinon in aqueous medium were developed using two types of lipase,
      from Candida Rugosa (microbial source) (CRL) and from porcine pancreas (animal
      source) (PPL) immobilized on functionalized gold electrode. Lipase is
      characterized to specifically catalyze the hydrolysis of ester functions leading
      to the transformation of diazinon into diethyl phosphorothioic acid (DETP) and 2
      isopropyl-4-methyl-6-hydroxypyrimidine (IMHP). The developed biosensors both
      presented a wide range of linearity up to 50 MUM with a detection limit of 10 nM
      for Candida Rugosa biosensor and 0.1 MUM for porcine pancreas biosensor. A
      comparative study was carried out between the two biosensors and results showed
      higher efficiency of Candida Rugosa sensor. Moreover, it presented good accuracy
      and reproducibility, had very good storage and multiple use stability for 25 days
      when stored at 4 degrees C. 

PMID- 25072054
TI  - TiO2@C core-shell nanoparticles formed by polymeric nano-encapsulation.
AB  - TiO2 semiconducting nanoparticles are known to be photocatalysts of moderate
      activity due to their high band-gap and high rate of electron-hole recombination.
      The formation of a shell of carbon around the core of TiO2, i.e., the formation
      of TiO2@C nanoparticles, is believed to partly alleviate these problems. It is
      usually achieved by a hydrothermal treatment in a presence of a sugar derivative.
      We present here a novel method for the formation of highly uniform C shell around
      TiO2 nanoparticles. For this purpose, TiO2 nanoparticles were dispersed in water
      using an oligomeric dispersant prepared by Reversible Addition-Fragmentation
      chain Transfer (RAFT) polymerization. Then the nanoparticles were engaged into an
      emulsion polymerization of acrylonitrile, resulting in the formation of a shell
      of polyacrylonitrile (PAN) around each TiO2 nanoparticles. Upon pyrolysis, the
      PAN was transformed into carbon, resulting in the formation of TiO2@C
      nanoparticles. The structure of the resulting particles was elucidated by X-Ray
      diffraction, FTIR, UV-VIS and Raman spectroscopy as well as TEM microscopy.
      Preliminary results about the use of the TiO2@C particles as photocatalysts for
      the splitting of water are presented. They indicate that the presence of the C
      shell is responsible for a significant enhancement of the photocurrent. 

PMID- 25072055
TI  - Association of MU-Opioid Activation in the Prefrontal Cortex with Spontaneous
      Migraine Attacks - Brief Report I.
AB  - We evaluated in vivo the MU-opioid system during spontaneous episodic migraine
      headaches. Seven patients were scanned at different phases of their migraine
      using Positron Emission Tomography with the selective MU-opioid receptor (MUOR)
      radiotracer [11C]carfentanil. In the ictal phase, there was MUOR activation in
      the medial prefrontal cortex, which was strongly associated with the MUOR
      availability level during the interictal phase. Furthermore, MU-opioid binding
      changes showed moderate negative correlation with the combined extension and
      severity of the attacks. These results indicate for the first time that there is
      high MUOR activation in the migraineurs' brains during headache attacks in
      response to their pain.

PMID- 25072053
TI  - Life without double-headed non-muscle myosin II motor proteins.
AB  - Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC)
      belong to a class of molecular motor proteins that are known to transduce
      cellular free-energy into biological work more efficiently than man-made
      combustion engines. Nature has given a single myosin II motor protein for lower
      eukaryotes and multiple for mammals but none for plants in order to provide
      impetus for their life. These specialized nanomachines drive cellular activities
      necessary for embryogenesis, organogenesis, and immunity. However, these
      multifunctional myosin II motor proteins are believed to go awry due to unknown
      reasons and contribute for the onset and progression of many autosomal-dominant
      disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and
      inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma
      viruses as well as Salmonella and Mycobacteria are now known to take hostage of
      these dedicated myosin II motor proteins for their efficient pathogenesis. Even
      after four decades since their discovery, we still have a limited knowledge of
      how these motor proteins drive cell migration and cytokinesis. We need to enrich
      our current knowledge on these fundamental cellular processes and develop novel
      therapeutic strategies to fix mutated myosin II motor proteins in pathological
      conditions. This is the time to think how to relieve the hijacked myosins from
      pathogens in order to provide a renewed impetus for patients' life. Understanding
      how to steer these molecular motors in proliferating and differentiating stem
      cells will improve stem cell based-therapeutics development. Given the plethora
      of cellular activities non-muscle myosin motor proteins are involved in, their
      importance is apparent for human life. 

PMID- 25072056
TI  - Facile one-pot synthesis of a aptamer-based organic-silica hybrid monolithic
      capillary column by "thiol-ene" click chemistry for detection of enantiomers of
      chemotherapeutic anthracyclines.
AB  - In the current study, we developed a facile strategy for the one-pot synthesis of
      an aptamer-based organic-silica hybrid monolithic capillary column. A 5'-SH
      modified aptamer, specifically targeting doxorubicin, was covalently modified in
      the hybrid silica monolithic column by a sol-gel method combined with "thiol-ene"
      click reaction. The prepared monolithic column had good stability and
      permeability, large specific surface, and showed excellent selectivity towards
      chemotherapeutic anthracyclines of doxorubicin and epirubicin. In addition, the
      enantiomers of doxorubicin and epirubicin can be easily separated by aptamer
      based affinity monolithic capillary liquid chromatography. Furthermore,
      doxorubicin and epirubicin spiked in serum and urine were also successfully
      determined, which suggested that the complex biological matrix had a negligible
      effect on the detection of doxorubicin and epirubicin. Finally, we quantified the
      concentration of epirubicin in the serum of breast cancer patients treated with
      epirubicin by intravenous injection. The developed analytical method is cost
      effective and rapid, and biological samples can be directly analyzed without any
      tedious sample pretreatment, which is extremely useful for monitoring medicines
      in serum and urine for pharmacokinetic studies. 

PMID- 25072057
TI  - Designing biomarker studies for head and neck cancer.
AB  - Although there is ample literature reporting on the identification of molecular
      biomarkers for head and neck squamous cell carcinoma, none is currently
      recommended for routine clinical use. A major reason for this lack of progress is
      the difficulty in designing studies in head and neck cancer to clearly establish
      the clinical utility of biomarkers. Consequently, biomarker studies frequently
      stall at the initial discovery phase. In this article, we focus on biomarkers for
      use in clinical management, including selection of therapy. Using several
      contemporary examples, we identify some of the common deficiencies in study
      design that hinder success in biomarker development for this disease area, and we
      suggest some potential solutions. The purpose of this article is to provide
      guidance that can assist investigators to more efficiently move promising
      biomarkers in head and neck cancer from discovery to clinical practice

PMID- 25072058
TI  - Liver abscess caused .

PMID- 25072060
TI  - 2.0 mg Intravitreal aflibercept as therapy for exudative age-related.

PMID- 25072061
TI  - MH17 tragedy: HIV community mourns loss of colleagues.

PMID- 25072062
TI  - Anthrax and smallpox errors highlight gaps in US biosafety.

PMID- 25072059
TI  - Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma
      in SCID mouse.
AB  - Rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20
      antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless,
      the relapsed/refractory rates are still high. One strategy to increase the
      clinical effectiveness of RTX is based on antibody-cytokine fusion protein
      (immunocytokine; ICK) vectorizing together at the tumor site the antibody
      effector activities and the cytokine co-signal required for the generation of
      cytotoxic cellular immunity. Such ICKs linking various antibody formats to
      interleukin (IL)-2 are currently being investigated in clinical trials and have
      shown promising results in cancer therapies. IL-15, a structurally-related
      cytokine, is now considered as having a better potential than IL-2 in antitumor
      immunotherapeutic strategies. We have previously engineered the fusion protein
      RLI, linking a soluble form of human IL-15Ralpha-sushi+ domain to human IL-15.
      Compared with IL-15, RLI displayed better biological activities in vitro and
      higher antitumor effects in vivo in murine and human cancer models. In this
      study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept
      its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully
      retained both antibody effector functions (ADCC and CDC), and the cytokine
      potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of
      disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term
      survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in
      combination, just delayed the disease onset (100% of death at 28, 40 and 51 days
      respectively). These findings suggest that such ICK could improve the clinical
      efficacy of RTX, particularly in patients with refractory B-cell lymphoma.

PMID- 25072063
TI  - UK general practice in crisis: time for a rethink?

PMID- 25072064
TI  - Polio provocation: solving a mystery with the help of history.

PMID- 25072065
TI  - Joep Lange.

PMID- 25072066
TI  - Primitive passion.

PMID- 25072068
TI  - Revised guidance on the choice of pertussis vaccines: July 2014.

PMID- 25072067
TI  - Chemoembolization outcomes for hepatocellular carcinoma in cirrhotic patients
      with compromised liver function.
AB  - BACKGROUND: Transarterial chemoembolization (TACE) is recommended as a treatment
      for unresectable hepatocellular carcinoma (HCC) in patients with normal
      underlying liver function. The efficacy of TACE in cirrhotic patients with
      compromised liver function is unknown. METHODS: All 'first' TACE interventions
      for HCC performed at a single institution from 2008 to 2012 were retrospectively
      reviewed (n = 190). Liver function was quantified via the Child's score. Tumour
      necrosis after TACE was quantified via the mRECIST criteria. RESULTS: The 'first'
      TACE procedures of 100 Child's A and 90 Child's B/C cirrhotic patients were
      evaluated. As expected, the lab-model for end-stage liver disease (MELD) score
      was significantly higher in the Child's B/C group. Although the number of tumours
      were similar between the groups, both the size of the largest tumour and the
      total tumour diameter were greater in the Child's A group. There were no
      significant differences in post-TACE tumour necrosis between groups. The median
      survival after TACE was significantly longer in the Child's A compared with
      Child's B/C patients (21.9 versus 13.7 months, P = 0.03). CONCLUSIONS: TACE
      appears to be equally efficacious in cirrhotic patients regardless of their
      Child's classification based upon equivalent mRECIST measures of tumour necrosis.
      However, inferior survival after TACE was observed in the Child's B/C group.

PMID- 25072069
TI  - WHO Global rotavirus surveillance  network - a strategic review of the  first 5
      years (2008-2012).

PMID- 25072070
TI  - Long-term results of canal wall reconstruction tympanomastoidectomy.
AB  - OBJECTIVES: This study was designed to evaluate the long-term results using the
      technique of canal wall reconstruction (CWR) tympanomastoidectomy with mastoid
      obliteration in the treatment of chronic otitis media with cholesteatoma. STUDY
      DESIGN: Institutional review board-approved retrospective case review. SETTING:
      Tertiary referral center. PATIENTS: Retrospective review was performed on
      consecutive patients undergoing CWR tympanomastoidectomy with mastoid
      obliteration at a single institution from 1997 to 2011. MAIN OUTCOME MEASURES:
      Status of tympanic membrane and ear canal anatomy, preoperative and postoperative
      audiometry,residual cholesteatoma at second look surgery, postoperative
      complications, recurrence rate, and location. RESULTS: Two hundred eighty-five
      ears in 273 patients underwent CWR tympanomastoidectomy with a mean age of 35
      years with average follow-up of 4.29 years (median, 3.16 yr).A second-look
      ossiculoplasty was performed in 253 (89%). Recurrent retraction pocket formation
      occurred in 34 ears (13%). A secondary endaural atticotomy only was required to
      improve access for debridement in 16 of these 34 ears (5.8% of total ears).Only 7
      ears (2.6%) required a revision open cavity mastoidectomy(n = 5) or subtotal
      petrosectomy (n = 2) for recurrent cholesteatoma. Those undergoing second-look
      ossiculoplasty demonstrated a small improvement in preoperative versus
      postoperative air-bone gap (ABG), 28 dB versus 23 dB, respectively.Postoperative
      infection occurred in 16 patients(5.6%) with 1 patient requiring conversion to
      open cavity mastoidectomy. CONCLUSION: A CWR tympanomastoidectomy provides
      excellent intraoperative exposure of the middle ear and mastoid without the long
      term disadvantages of a canal wall down mastoidectomy. Long-term follow-up
      demonstrates that there were only 2.6% failures requiring conversion to an open
      cavity or subtotal petrosectomy.

PMID- 25072071
TI  - [Overdiagnosis and overtreatment in psychiatry?].

PMID- 25072072
TI  - [The importance of weighing yourself regularly. Dr. Fox and the weight curve].

PMID- 25072073
TI  - [Fat intake and heart disease in controversial meta-analysis. Study with too many
      shortcomings--former fat recommendation remains unchanged].

PMID- 25072074
TI  - [Risk factors for remaining pain after orthopedic surgery].

PMID- 25072075
TI  - [Fast track has its advantages in elective gynecological surgery].

PMID- 25072076
TI  - [Potential organ donors are missed at county hospitals. Medical record review
      study from Mora hospital].

PMID- 25072077
TI  - [Primary health care in Kronoberg before and after the care choice. More
      satisfied patients ... the staff think it got worse].

PMID- 25072078
TI  - [Evaluation of patients with chest pain: Can we settle with measurement of
      troponin only on arrival?].

PMID- 25072079
TI  - [HEART-score does not improve the risk assessment].

PMID- 25072080
TI  - [Bill Gates and the lack of student influence on Karolinska Institutet].

PMID- 25072081
TI  - Fight looming over health budget cuts.

PMID- 25072082
TI  - Nurses and midwives march in May.

PMID- 25072083
TI  - Depression risk for young mums.

PMID- 25072084
TI  - Decision hurts nurses and midwives.

PMID- 25072085
TI  - Health care innovation.

PMID- 25072086
TI  - Needlestick injuries avoidable.

PMID- 25072087
TI  - Images to breakdown stereotypes.

PMID- 25072088
TI  - Have your say: privately practising midwives.

PMID- 25072089
TI  - Celebrating nurses and midwives.

PMID- 25072090
TI  - Cut salt to save lives.

PMID- 25072091
TI  - Pap test could be scrapped.

PMID- 25072092
TI  - Aussie kids not getting enough exercise.

PMID- 25072093
TI  - Call for safe staffing levels in UK.

PMID- 25072094
TI  - Racism concerns in american health care.

PMID- 25072095
TI  - Getting hospital boards on board.

PMID- 25072096
TI  - Another perspective.

PMID- 25072097
TI  - On-tissue localization of ceramides and other sphingolipids by MALDI mass
      spectrometry imaging.
AB  - A novel MALDI-FTICR imaging mass spectrometry (MALDI-IMS) workflow is described
      for on-tissue detection, spatial localization, and structural confirmation of low
      abundance bioactive ceramides and other sphingolipids. Increasingly, altered or
      elevated levels of sphingolipids, sphingolipid metabolites, and sphingolipid
      metabolizing enzymes have been associated with a variety of disorders such as
      diabetes, obesity, lysosomal storage disorders, and cancer. Ceramide, which
      serves as a metabolic hub in sphingolipid metabolism, has been linked to cancer
      signaling pathways and to metabolic regulation with involvement in autophagy,
      cell-cycle arrest, senescence, and apoptosis. Using kidney tissues from a new
      Farber disease mouse model in which ceramides of all acyl chain lengths and other
      sphingolipid metabolites accumulate in tissues, specific ceramides and
      sphingomyelins were identified by on-tissue isolation and fragmentation, coupled
      with an on-tissue digestion by ceramidase or sphingomyelinase. Multiple
      glycosphingolipid species were also detected. The newly generated library of
      sphingolipid ions was then applied to MALDI-IMS of human lung cancer tissues.
      Multiple tumor specific ceramide and sphingomyelin species were detected and
      confirmed by on-tissue enzyme digests and structural confirmation. High
      resolution MALDI-IMS in combination with novel on-tissue ceramidase and
      sphingomyelinase enzyme digestions makes it now possible to rapidly visualize the
      distribution of bioactive ceramides and sphingomyelin in tissues. 

PMID- 25072099
TI  - Highly controllable and stable quantized conductance and resistive switching
      mechanism in single-crystal TiO2 resistive memory on silicon.
AB  - TiO2 is being widely explored as an active resistive switching (RS) material for
      resistive random access memory. We report a detailed analysis of the RS
      characteristics of single-crystal anatase-TiO2 thin films epitaxially grown on
      silicon by atomic layer deposition. We demonstrate that although the valence
      change mechanism is responsible for the observed RS, single-crystal anatase-TiO2
      thin films show electrical characteristics that are very different from the usual
      switching behaviors observed for polycrystalline or amorphous TiO2 and instead
      very similar to those found in electrochemical metallization memory. In addition,
      we demonstrate highly stable and reproducible quantized conductance that is well
      controlled by application of a compliance current and that suggests the localized
      formation of conducting Magneli-like nanophases. The quantized conductance
      observed results in multiple well-defined resistance states suitable for
      implementation of multilevel memory cells. 

PMID- 25072098
TI  - Beyond cigarettes per day. A genome-wide association study of the biomarker
      carbon monoxide.
AB  - RATIONALE: The CHRNA5-CHRNA3-CHRNB4 locus is associated with self-reported
      smoking behavior and also harbors the strongest genetic associations with chronic
      obstructive pulmonary disease (COPD) and lung cancer. Because the associations
      with lung disease remain after adjustment for self-reported smoking behaviors, it
      has been asserted that CHRNA5-CHRNA3-CHRNB4 variants increase COPD and lung
      cancer susceptibility independently of their effects on smoking. OBJECTIVES: To
      compare the genetic associations of exhaled carbon monoxide (CO), a biomarker of
      current cigarette exposure, with self-reported smoking behaviors. METHODS: A
      total of 1,521 European American and 247 African American current smokers
      recruited into smoking cessation studies were assessed for CO at intake before
      smoking cessation. DNA samples were genotyped using the Illumina Omni2.5
      microarray. Genetic associations with CO and smoking behaviors (cigarettes smoked
      per day, Fagerstrom test for nicotine dependence) were studied. MEASUREMENTS AND
      MAIN RESULTS: Variants in the CHRNA5-CHRNA3-CHRNB4 locus, including rs16969968, a
      nonsynonymous variant in CHRNA5, are genomewide association study-significantly
      associated with CO (beta = 2.66; 95% confidence interval [CI], 1.74-3.58; P =
      1.65 * 10(-8)), and this association remains strong after adjusting for smoking
      behavior (beta = 2.18; 95% CI, 1.32-3.04; P = 7.47 * 10(-7)). The correlation
      between CO and cigarettes per day is statistically significantly lower (z = 3.43;
      P = 6.07 * 10(-4)) in African Americans (r = 0.14; 95% CI, 0.02-0.26; P = 0.003)
      than in European-Americans (r = 0.36; 95% CI, 0.31-0.40; P = 0.0001).
      CONCLUSIONS: Exhaled CO, a biomarker that is simple to measure, captures aspects
      of cigarette smoke exposure in current smokers beyond the number of cigarettes
      smoked per day. Behavioral measures of smoking are therefore insufficient indices
      of cigarette smoke exposure, suggesting that genetic associations with COPD or
      lung cancer that persist after adjusting for self-reported smoking behavior may
      still reflect genetic effects on smoking exposure.

PMID- 25072101
TI  - pbs quantum dots capped with amorphous ZnS for bulk heterojunction solar cells:
      the solvent effect.
AB  - In this study, two distinct structures of PbS quantum dots (QDs) are produced
      with amorphous ZnS as the capping material by successive ionic layer adsorption
      and reaction. With methanolic solution, spherical PbS QDs (~5 nm) are embedded in
      the ZnS matrix (i.e., embedding structure), exhibiting relatively large distance
      between the QDs. With aqueous solution, irregularly shaped PbS QDs (<3 nm) blend
      intimately with the ZnS medium (i.e., blending structure), showing indiscernible
      QD spacing. This is attributed to a relatively low reactivity of Pb(2+) ions in
      water, suppressing quantum dot growth in the mesopores. Bulk heterojunction of
      mesoporous TiO2 substrate filled up with the blending configuration shows
      superior photovoltaic performance to the embedding architecture, because of the
      small QD size and close distance between the QDs. 

PMID- 25072100
TI  - Targeted nanogel conjugate for improved stability and cellular permeability of
      curcumin: synthesis, pharmacokinetics, and tumor growth inhibition.
AB  - Curcumin (CUR) is a unique natural compound with promising anticancer and anti
      inflammatory activities. However, the therapeutic efficacy of curcumin was
      challenged in clinical trials, mostly due to its low bioavailability, rapid
      metabolism, and elimination. We designed a nanodrug form of curcumin, which makes
      it stable and substantially enhances cellular permeability and anticancer
      activity at standard oral administration. Curcumin was conjugated as an ester to
      cholesteryl-hyaluronic acid (CHA) nanogel that is capable of targeted delivery to
      CD44-expressing drug-resistant cancer cells. CHA-CUR nanogels demonstrated
      excellent solubility and sustained drug release in physiological conditions. It
      induced apoptosis in cancer cells, suppressing the expression of NF-kappaB, TNF
      alpha, and COX-2 cellular targets similar to free curcumin.
      Pharmacokinetic/pharmacodynamic (PK/PD) studies also revealed improved
      circulation parameters of CHA-CUR at oral, i.p. and i.v. administration routes.
      CHA-CUR showed targeted tumor accumulation and effective tumor growth inhibition
      in human pancreatic adenocarcinoma MiaPaCa-2 and aggressive orthotropic murine
      mammary carcinoma 4T1 animal models. CHA-CUR treatment was well-tolerated and
      resulted in up to 13-fold tumor suppression, making this nanodrug a potential
      candidate for cancer prevention and therapeutic treatment. 

PMID- 25072102
TI  - Temporal variations of cyclic and linear volatile methylsiloxanes in the
      atmosphere using passive samplers and high-volume air samplers.
AB  - Cyclic and linear volatile methylsiloxanes (cVMSs and lVMSs, respectively) were
      measured in ambient air over a period of over one year in Toronto, Canada. Air
      samples were collected using passive air samplers (PAS) consisting of sorbent
      impregnated polyurethane foam (SIP) disks in parallel with high volume active air
      samplers (HV-AAS). The average difference between the SIP-PAS derived
      concentrations in air for the individual VMSs and those measured using HV-AAS was
      within a factor of 2. The air concentrations (HV-AAS) ranged 22-351 ng m(-3) and
      1.3-15 ng m(-3) for SigmacVMSs (D3, D4, D5, D6) and SigmalVMSs (L3, L4, L5),
      respectively, with decamethylcyclopentasiloxane (D5) as the dominant compound
      (~75% of the SigmaVMSs). Air masses arriving from north to northwest (i.e., less
      populated areas) were significantly less contaminated with VMSs compared to air
      arriving from the south that are impacted by major urban and industrial areas in
      Canada and the U.S. (p < 0.05). In addition, air concentrations of SigmacVMSs
      were lower during major snowfall events (on average, 73 ng m(-3)) in comparison
      to the other sampling periods (121 ng m(-3)). Ambient temperature had a small
      influence on the seasonal trend of VMS concentrations in air, except for
      dodecamethylcyclohexasiloxane (D6), which was positively correlated with the
      ambient temperature (p < 0.001). 

PMID- 25072103
TI  - Metabolic syndrome: prevalence and association with electrocardiographic
      abnormalities in Nigerian hypertensive patients.
AB  - BACKGROUND: Hypertension is an important component of metabolic syndrome, and a
      third of hypertensive patients have metabolic syndrome, with the common
      mechanistic pathway believed to be insulin resistance. It is probable that
      hypertensive patients with metabolic syndrome will have more severe cardiac
      abnormalities than those without. Similarly, electrocardiogram (ECG)
      abnormalities have serious implications for cardiovascular disease outcome. Data
      on association between metabolic syndrome and ECG abnormalities are scarce in
      Nigeria. This study aimed to assess the prevalence of metabolic syndrome and its
      components in hypertensive patients and possible association of metabolic
      syndrome with ECG abnormalities in them. MATERIALS AND METHODS: One hundred and
      thirty-five new adult hypertensive patients were studied in a hospital-based
      cross-sectional study. Metabolic syndrome prevalence was estimated by National
      Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria.
      ECG abnormalities were divided into minor and major abnormalities based on
      Novacode. SPSS IBM 20 was used to analyze data. RESULTS: Mean age was 59.19 +/-
      13.33 (30-75 years). Metabolic syndrome prevalence was 40.74% (28.85% in males;
      48.19% in females). Abnormal waist circumference (58.51%) was the commonest
      additional component of metabolic syndrome in these patients. ECG abnormalities
      were in 77.78% of the population, with 49.63% and 28.15% being minor and major
      abnormalities, respectively. There was no significant association between
      metabolic syndrome and ECG abnormalities in these patients. CONCLUSION:
      Prevalence of metabolic syndrome in hypertensive patients was high, central
      obesity being the commonest component of the syndrome. The high prevalence of ECG
      abnormalities may be more a reflection of the presence of hypertension than any
      other component of the syndrome.

PMID- 25072104
TI  - Electronic structure and slow magnetic relaxation of low-coordinate cyclic
      alkyl(amino) carbene stabilized iron(I) complexes.
AB  - Cyclic alkyl(amino) carbene stabilized two- and three-coordinate Fe(I) complexes,
      (cAAC)2FeCl (2) and [(cAAC)2Fe][B(C6F5)4] (3), respectively, were prepared and
      thoroughly studied by a bouquet of analytical techniques as well as theoretical
      calculations. Magnetic susceptibility and Mossbauer spectroscopy reveal the +1
      oxidation state and S = 3/2 spin ground state of iron in both compounds. 2 and 3
      show slow magnetic relaxation typical for single molecule magnets under an
      applied direct current magnetic field. The high-frequency EPR measurements
      confirm the S = 3/2 ground state with a large, positive zero-field splitting
      (~20.4 cm(-1)) and reveal easy plane anisotropy for compound 2.
      CASSCF/CASPT2/RASSI-SO ab initio calculations using the MOLCAS program package
      support the experimental results. 

PMID- 25072105
TI  - Spectroscopic quantification of 5-hydroxymethylcytosine in genomic DNA.
AB  - 5-Hydroxymethylcytosine (5hmC), a modified form of the DNA base cytosine, is an
      important epigenetic mark linked to regulation of gene expression in development,
      and tumorigenesis. We have developed a spectroscopic method for a global
      quantification of 5hmC in genomic DNA. The assay is performed within a multiwell
      plate, which allows simultaneous recording of up to 350 samples. Our
      quantification procedure of 5hmC is direct, simple, and rapid. It relies on a two
      step protocol that consists of enzymatic glucosylation of 5hmC with an azide
      modified glucose, followed by a "click reaction" with an alkyne-fluorescent tag.
      The fluorescence intensity recorded from the DNA sample is proportional to its
      5hmC content and can be quantified by a simple plate reader measurement. This
      labeling technique is specific and highly sensitive, allowing detection of 5hmC
      down to 0.002% of the total nucleotides. Our results reveal significant
      variations in the 5hmC content obtained from different mouse tissues, in
      agreement with previously reported data. 

PMID- 25072106
TI  - Preliminary Normative Data on the Penn State University Symbol Cancellation Task
      With Nonconcussed Adolescents.
AB  - Visual concentration impairment after neurologic injury is frequent, making its
      identification a critical component of neurocognitive concussion assessment.
      Visual target cancellation tests such as the Penn State University Symbol
      Cancellation Task (PSUSCT) have been widely used in assessing professional and
      collegiate athletes. To date, there are no normative studies using the PSUSCT
      with an adolescent population. Given that 38 million children and adolescents
      participate in sports and an estimated 5% to 10% are concussed annually,
      adolescent normative data are critically needed to evaluate concussions in this
      vulnerable population. The purpose of this study was to provide adolescent
      normative data on the PSUSCT. Participants included 40 healthy, nonconcussed high
      school students aged 14 to 19 years old (20 men, 20 women). Participants were
      administered Forms A and C of the PSUSCT within a 4-day period. Data analysis
      examined hits, omission errors, and commission errors, with descriptive
      statistics calculated for the total sample and for subgroups by gender and age.
      Study 1 provided normative adolescent data on Form A. Study 2 examined practice
      effects and established reliable change indexes (RCIs) by comparing results on
      Forms A and C. Neither Study 1 nor Study 2 demonstrated significant group
      differences for gender or age. In conclusion, this study presents adolescent
      normative data, apparent practice effects, and RCIs on the PSUSCT. These norms
      provide data needed to appropriately include the PSUSCT in baseline and
      postinjury concussion evaluation batteries with adolescent student-athletes.
      Findings should be replicated with a larger, more heterogeneous sample. 

PMID- 25072107
TI  - Rationally induced RNA:DNA G-quadruplex structures elicit an anticancer effect by
      inhibiting endogenous eIF-4E expression.
AB  - RNA G-quadruplex (GQ) structures act as regulators of a diverse array of cellular
      processes including translation, pre-mRNA processing, and mRNA targeting. We
      report here a strategy of harnessing the natural ability of RNA GQs to inhibit
      translation by rationally inducing a GQ on a targeted mRNA to knockdown
      endogenous gene expression. We chose to target eIF-4E because of its key role in
      translation initiation and overexpression in multiple cancers and with the
      expectation that downregulation of eIF-4E would result in antiproliferation of
      cancer cells. Targeted hybrid (RNA:DNA) GQ structures were induced at the 5'
      untranslated region (UTR) and the protein coding region of the eIF-4E mRNA by
      rationally designed and partially modified extraneous DNA sequences and their
      effect on eIF-4E expression was determined. The formation of a stable induced G
      quadruplex was established by biophysical and biochemical methods. Thermodynamic
      parameters calculated from CD melting indicate formation of a stable induced GQ
      at a physiologically relevant salt concentration. We established the specificity
      and efficacy of the induced GQ formation by monitoring the targeted repression of
      a reporter gene. Most importantly we have demonstrated that inducing GQ in the 5'
      UTR and the protein coding region of eIF-4E mRNA in human cancer cells results in
      30% and 60% inhibition of the endogenous protein expression, respectively.
      Treating with the GQ inducing oligonucleotide sequences resulted in a decrease in
      the viability of human cancer cells in a dose-dependent manner. The above concept
      opens up a new strategy for targeted modulation of endogenous gene expression. 

PMID- 25072108
TI  - Cyclic Hexapeptides from the Deep South China Sea-Derived Streptomyces
      scopuliridis SCSIO ZJ46 Active Against Pathogenic Gram-Positive Bacteria.
AB  - Three new cyclohexapeptides, desotamides B-D (2-4), and the known desotamide (1)
      were isolated from marine microbe Streptomyces scopuliridis SCSIO ZJ46. The
      sequences and absolute configurations of 2-4 were elucidated on the basis of high
      resolution spectroscopic data, Marfey's method, and chiral-phase HPLC data.
      Desotamide C (3) contains a unique N-formyl-kynurenine residue, whereas 4 lacks
      formylation at the same site. Compounds 1 and 2 displayed notable antibacterial
      activities against strains of Streptococcus pnuemoniae, Staphylococcus aureus,
      and methicillin-resistant Staphylococcus epidermidis (MRSE), and structure
      activity relationship studies revealed the indispensability of the Trp component
      for antibacterial activity within this new scaffold. 

PMID- 25072109
TI  - Determination of hexamethylenetetramine in foods by high-performance liquid
      chromatography (HPLC).
AB  - A simple and rapid method was developed and validated for the determination of
      hexamethylenetetramine (HMT) in foods. Samples were homogenised and extracted
      with methanol, followed by centrifugation. The resulting solution was filtered
      and injected into the high-performance liquid chromatograph (HPLC). HMT was
      separated using a Zorbax SCX-300 column coupled to a photodiode array detector.
      The calibration curve was linear in the range of 1.0-100 MUg ml(-1), with good
      correlation coefficients (r(2) = 0.9992). The recoveries of HMT from foods spiked
      at levels of 10, 50 and 100 mg kg(-1) ranged from 91.6% to 103.8%, with relative
      standard deviations (RSDs) between 0.9% and 5.3%. The limit of detection and the
      limit of quantification of HMT were 0.3 and 1.0 mg kg(-1) based on three food
      matrixes (provolone cheese, glass noodle and tofu snack), respectively.
      Uncertainty associated with accuracy contributed mostly to the expanded
      uncertainty. No detectable levels of HMT were found in any of the samples
      retailed in Korea. The method was successful in determining HMT in foods.

PMID- 25072110
TI  - Soluble vascular endothelial growth factor receptor-1 improves therapeutic
      efficacy of suicide gene therapy in an angiogenesis-independent manner.
AB  - Abstract Malignant gliomas (MGs) are highly vascularized, aggressive brain
      cancers carrying a dismal prognosis. Because of their high vascularity, anti
      angiogenic therapy is a potential treatment option. Indeed, the anti-vascular
      endothelial growth factor (VEGF) antibody bevacizumab has demonstrated promising
      results in clinical trials. Similarly, adenovirus-medicated Herpes simplex virus
      thymidine kinase and ganciclovir (AdHSV-tk/GCV) suicide gene therapy has
      established itself in clinical trials as a potential novel therapeutic strategy
      for MGs. In this study, we demonstrate the feasibility of combining adenovirus
      mediated soluble VEGF receptor-1 anti-angiogenic gene therapy with AdHSV-tk/GCV
      suicide gene therapy to treat experimental MGs. Our results reveal that, apart
      from inhibiting angiogenesis, other anti-tumor mechanisms, such as reduction of
      infiltration by tumor-associated macrophages/microglia, may contribute to the
      improved therapeutic benefit of combination therapy. 

PMID- 25072111
TI  - The role of antiplatelet medications in angiogram-negative subarachnoid
      hemorrhage.
AB  - BACKGROUND: The use of antiplatelet medications has greatly expanded and this has
      been associated with an increased rate of complications after aneurysmal
      subarachnoid hemorrhage (SAH). The influence of antiplatelet medications on
      outcomes after non-aneurysmal SAH is unknown. OBJECTIVE: To analyze the frequency
      and impact on outcome of antiplatelet medication use among patients with
      angiogram-negative SAH. METHODS: An analysis of patients within the Columbia
      University SAH Outcomes Project database was performed. All patients who
      underwent catheter cerebral angiography after presenting with nontraumatic SAH
      between 1996 and 2013 were included. Outcomes were assessed by using the modified
      Rankin Scale. RESULTS: A total of 1351 patients underwent catheter angiography
      for evaluation of SAH. Of these, 173 (13%) were designated angiogram-negative.
      The fraction of patients presenting with angiogram-negative SAH as well as the
      frequency of antiplatelet use among these patients significantly increased during
      the study period. Antiplatelet use was more commonly associated with angiogram
      negative SAH than with angiogram-positive SAH (27% vs 14%, P = .001). At 14 days
      after presentation, poor outcome was significantly more frequent among patients
      who took antiplatelet agents than among those who did not (38% vs 20%, P = .017).
      This effect was also seen after multivariate analysis (odds ratio, 2.58; P =
      .034), although no difference was observed by 12 months (P > .05). CONCLUSION:
      Antiplatelet medication use is associated with poor early, but not late, outcomes
      after angiogram-negative SAH. Corresponding increased rates of antiplatelet
      medication use and angiogram-negative SAH may be related. Additional studies are
      needed to confirm this association.

PMID- 25072112
TI  - Phase I clinical trial for the feasibility and safety of remote ischemic
      conditioning for aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Remote ischemic conditioning (RIC) is a powerful endogenous mechanism
      whereby a sublethal ischemic stimulus confers a protective benefit against a
      subsequent severe ischemic insult. RIC has significant potential clinical
      implications for the prevention of delayed ischemic neurological deficit after
      aneurysmal subarachnoid hemorrhage (aSAH). Although RIC has been extensively
      investigated in animal models, it has not been fully evaluated in humans.
      OBJECTIVE: To assess the feasibility and safety of RIC for aSAH in a phase I
      clinical trial. METHODS: Consecutive patients hospitalized for treatment of an
      aSAH who met the inclusion/exclusion criteria were approached for consent.
      Enrolled patients received up to 4 RIC sessions on nonconsecutive days. Primary
      end points were the development of a symptomatic deep venous thrombosis,
      bruising, or injury to the limb and request to stop by the patient or surrogate.
      The secondary end points were the development of new neurological deficits or
      cerebral infarct, demonstrated by brain imaging after enrollment, and
      neurological deficit and condition at follow-up. RESULTS: Twenty patients were
      enrolled and underwent 76 RIC sessions, 75 of which were completed successfully.
      One session was discontinued when the patient became confused. No patient
      developed a deep venous thrombosis or injury to the preconditioned limb. No
      patient developed delayed ischemic neurological deficit during enrollment. At
      follow-up, median modified Rankin Scale score was 1 and Glasgow Outcome Scale
      score was 5. CONCLUSION: The RIC procedure was well tolerated and did not cause
      any injury. RIC for aSAH warrants investigation in a subsequent pivotal clinical
      trial.

PMID- 25072113
TI  - Ultrasound-guided needle localization of the saphenous nerve for removal of
      neuroma in the infrapatellar branches: technical report.
AB  - BACKGROUND: Neuromata formation in the infrapatellar branch of the saphenous
      nerve (IPBSN) has been well described as a potential complication of arthroscopic
      knee surgery and knee trauma. Resection has been proven to provide improvement of
      pain and increased range of motion. Currently, physical examination and surgical
      exploration based on anatomic landmarks are the standard for intraoperative
      localization of IPBSN neuromas. OBJECTIVE: To demonstrate the anatomy of the
      IPSBN and the use of preoperative ultrasound and needle placement for
      localization of the nerve before sectioning. METHODS: Using both anatomic
      dissections and the combination of preoperative ultrasound and curved-needle
      placement, we demonstrate the technical nuances to localize the IPBSN before
      operative section. RESULTS: Cadaveric dissection is used to illustrate the main
      trunk of the IPSBN and its branches. In 2 cases, ultrasound guidance was
      effectively used to localize the saphenous nerve and its branches and facilitate
      the operative treatment of patients with symptomatic IPBSN neuromas. CONCLUSION:
      Ultrasound is a widely accepted and commonly utilized imaging modality; however,
      in this report, ultrasound-guided needle localization was used to aid in the
      resection of neuromas of small, painful sensory nerves.

PMID- 25072114
TI  - Letter: the "over the wire" technique for ventricular catheter revision and a
      proposed access kit for this purpose.

PMID- 25072115
TI  - Navigated transcranial magnetic stimulation for "somatotopic" tractography of the
      corticospinal tract.
AB  - BACKGROUND: Diffusion tensor imaging tractography provides 3-dimensional
      reconstruction of principal white matter tracts, but its spatial accuracy has
      been questioned. Navigated transcranial magnetic stimulation (nTMS) enables
      somatotopic mapping of the motor cortex. OBJECTIVE: We used motor maps to
      reconstruct the corticospinal tract (CST) by integrating elements of its
      somatotopic organization. We analyzed the accuracy of this method compared with a
      standard technique and verified its reliability with intraoperative subcortical
      stimulation. METHODS: We prospectively collected data from patients who underwent
      surgery between January 2012 and October 2013 for lesions involving the CST. nTMS
      based diffusion tensor imaging tractography was compared with a standard
      technique. The reliability and accuracy between the 2 techniques were analyzed by
      comparing the number of fibers, the concordance in size, and the location of the
      cortical end of the CST and the motor area. The accuracy of the technique was
      assessed by using direct subcortical stimulation. RESULTS: Twenty patients were
      enrolled in the study. nTMS-based tractography provided a detailed somatotopic
      reconstruction of the CST. This nTMS-based reconstruction resulted in a decreased
      number of fibers (305.1+/-231.7 vs 1024+/-193, P<.001) and a significantly
      greater overlap between the motor cortex and the cortical end-region of the CST
      compared with the standard technique (90.5+/-8.8% vs 58.3+/-16.6%, P<.001).
      Direct subcortical stimulation confirmed the CST location and the somatotopic
      reconstruction in all cases. CONCLUSION: These results suggest that nTMS-based
      tractography of the CST is more accurate and less operator dependent than the
      standard technique and provides a reliable anatomic and functional
      characterization of the motor pathway.

PMID- 25072117
TI  - 4,4',5,5'-Tetracarboxy-2,2'-bipyridine Ru(II) sensitizers for dye-sensitized
      solar cells.
AB  - Two Ru(II) sensitizers TCR-1 and TCR-2 bearing four carboxy anchoring groups were
      prepared using 4,4',5,5'-tetraethoxycarbonyl-2,2'-bipyridine chelate and 4-(5
      hexylthien-2-yl)-2-(3-trifluoromethyl-1H-pyrazol-5-yl)pyridine and 6-t-butyl-1-(3
      trifluoromethyl-1H-pyrazol-5-yl)isoquinoline, respectively. Dissolution of these
      sensitizers in DMF solution afforded a light green solution up to 10(-5) M, for
      which their color gradually turned red upon further dilution and deposition on
      the surface of a TiO2 photoanode due to the spontaneous deprotonation of
      carboxylic acid groups. These sensitizers were characterized using
      electrochemical means and structural analysis time-dependent density functional
      theory (TDDFT) simulation and were also subjected to actual device fabrication.
      The as-fabricated DSC devices showed overall efficiencies eta = 6.16% and 6.23%
      versus their 4,4'-dicarboxy counterparts TFRS-2 and TFRS-52 with higher
      efficiencies of 7.57% and 8.09%, using electrolyte with 0.2 M LiI additive. Their
      inferior efficiencies are possibly caused by the combination of blue-shifted
      absorption on TiO2, inadequate dye loading, and the perpendicularly oriented
      central carboxy groups. 

PMID- 25072118
TI  - Diabetic nephropathy: Heparanase mediates renal injury.

PMID- 25072119
TI  - Immunization after kidney transplantation-what is necessary and what is safe?
AB  - Many transplant recipients are not protected against vaccine-preventable
      illnesses, primarily because vaccination is still an underutilized tool both
      before and after transplantation. This missed opportunity for protection can
      result in substantial morbidity, graft loss and mortality. Immunization
      strategies should be formulated early in the course of renal disease to maximize
      the likelihood of vaccine-induced immunity, particularly as booster or secondary
      antibody responses are less affected by immune compromise than are primary or de
      novo antibody responses in naive vaccine recipients. However, live vaccines
      should be avoided in immunocompromised hosts. Although some concern has been
      raised regarding increased HLA sensitization after vaccination, no clinical data
      to suggest harm currently exists; overall, non-live vaccines seem to be
      immunogenic, protective and safe. In organ transplant recipients, some vaccines
      are indicated based on specific risk factors and certain vaccines, such as
      hepatitis B, can protect against donor-derived infection. Vaccines given to close
      contacts of renal transplant recipients can provide an additional layer of
      protection against infectious diseases. In this article, optimal vaccination of
      adult transplant recipients, including safety, efficacy, indication and timing,
      is reviewed. 

PMID- 25072120
TI  - Renin-angiotensin system: Targeting multiple RAS genes.

PMID- 25072116
TI  - Targeting human dendritic cells in situ to improve vaccines.
AB  - Dendritic cells (DCs) provide a critical link between innate and adaptive
      immunity. The potent antigen presenting properties of DCs makes them a valuable
      target for the delivery of immunogenic cargo. Recent clinical studies describing
      in situ DC targeting with antibody-mediated targeting of DC receptor through DEC
      205 provide new opportunities for the clinical application of DC-targeted
      vaccines. Further advances with nanoparticle vectors which can encapsulate
      antigens and adjuvants within the same compartment and be targeted against
      diverse DC subsets also represent an attractive strategy for targeting DCs. This
      review provides a brief summary of the rationale behind targeting dendritic cells
      in situ, the existing pre-clinical and clinical data on these vaccines and
      challenges faced by the next generation DC-targeted vaccines. 

PMID- 25072121
TI  - Acute kidney injury: Antibiotic therapy during CRRT--getting the dose just right.

PMID- 25072123
TI  - Intralesional cryosurgery combined with topical silicone gel sheeting for the
      treatment of refractory keloids.
AB  - BACKGROUND: A variety of therapeutic procedures for treating keloids have been
      previously reported, with varying success and recurrence rates. As a monotherapy,
      intralesional cryosurgery has yielded convincing clinical results. OBJECTIVE: We
      combined intralesional cryosurgery with the application of topical silicone gel
      sheeting. MATERIALS AND METHODS: In this retrospective study, which was conducted
      between 2008 and 2012, 21 patients with 32 keloids were enrolled. Twenty-five
      lesions were treated with intralesional cryotherapy combined with postoperative
      silicone gel sheeting (the cryotherapy + silicone group), and 7 keloids were
      treated with intralesional cryotherapy alone (the cryotherapy group). The scar
      volume reduction was assessed, and the patients' subjective and objective
      parameters were evaluated. Additionally, patient satisfaction was estimated using
      a modified Gorney Gram scale (0-3). RESULTS: In all cases (n = 32 for both
      groups), a significant keloid volume reduction was observed. The patients'
      subjective complaints were significantly improved, whereas the combined therapy
      showed slightly better results in hardness (p < .0012), pain (p < .0233), and
      discomfort (p < .0029), whereas monotherapy achieved higher satisfaction scores
      in redness (p < .0220) and pruritus (p < .0206), although these differences were
      not significant between the treatment modalities. CONCLUSION: The results of this
      study support the use of combined intralesional cryosurgery followed by the
      application of silicone gel sheeting to treat refractory keloids.

PMID- 25072124
TI  - Free cartilage batten graft with second intention healing to repair a full
      thickness alar wound.

PMID- 25072125
TI  - Current systemic therapies for melanoma.
AB  - BACKGROUND: Systemic agents are used in melanoma for adjuvant therapy and to
      treat metastatic disease. Currently, interferon-alpha is the only agent approved
      for adjuvant therapy. Six drugs are FDA approved for metastatic disease:
      dacarbazine, interleukin-2 (IL-2), vemurafenib, ipilimumab, dabrafenib, and
      trametinib. Vemurafenib and ipilimumab were approved in 2011, whereas dabrafenib
      and trametinib were approved in 2013. OBJECTIVE: This review will update the
      practicing dermatologist on the differences in efficacy, adverse events, and cost
      of systemic therapies available for the treatment of melanoma. MATERIALS AND
      METHODS: This article is a review of the current literature on systemic therapies
      for advanced melanoma. Key search words included "advanced melanoma," "systemic
      therapy," and "adjuvant therapy" with particular focus on the past 20 years.
      RESULTS: Before 2011, dacarbazine and IL-2 were the only FDA approved therapies
      for metastatic melanoma, and IFN-alpha is the only approved agent for adjuvant
      therapy. The new agents vemurafenib, ipilimumab, dabrafenib, and trametinib are
      the first to have improved overall survival in Phase III studies in comparison
      with other systemic therapies. CONCLUSION: Despite new developments, there
      remains a significant need for better therapies with improved long-term efficacy
      and decreased toxicity.

PMID- 25072122
TI  - Henoch-Schonlein purpura nephritis in children.
AB  - Henoch-Schonlein purpura (HSP) is the most common vasculitis in children, in whom
      prognosis is mostly dependent upon the severity of renal involvement. Nephritis
      is observed in about 30% of children with HSP. Renal damage eventually leads to
      chronic kidney disease in up to 20% of children with HSP nephritis in tertiary
      care centres, but in less than 5% of unselected patients with HSP, by 20 years
      after diagnosis. HSP nephritis and IgA nephropathy are related diseases resulting
      from glomerular deposition of aberrantly glycosylated IgA1. Although both
      nephritides present with similar histological findings and IgA abnormalities,
      they display pathophysiological differences with important therapeutic
      implications. HSP nephritis is mainly characterized by acute episodes of
      glomerular inflammation with endocapillary and mesangial proliferation, fibrin
      deposits and epithelial crescents that can heal spontaneously or lead to chronic
      lesions. By contrast, IgA nephropathy normally presents with slowly progressive
      mesangial lesions resulting from continuous low-grade deposition of
      macromolecular IgA1. This Review highlights the variable evolution of similar
      clinical and histological presentations among paediatric patients with HSP
      nephritis, which constitutes a challenge for their management, and discusses the
      treatment of these patients in light of current guidelines based on clinical
      evidence from adults with IgA nephropathy. 

PMID- 25072126
TI  - Effective blue light photodynamic therapy does not affect cutaneous langerhans
      cell number or oxidatively damage DNA.
AB  - BACKGROUND: Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue
      light or red light is effective for treating actinic keratoses (AKs). However,
      immunosuppression follows red light PDT, raising the spectre of skin cancer
      promotion in treated skin. OBJECTIVE: To determine whether broad-area short
      incubation (BASI)-ALA-PDT using blue light immunosuppression immunosuppresses
      treated skin. METHODS: Patients were evaluated clinically and by standardized
      facial biopsies of non-AK skin before, 24 hours and 1 month after customary blue
      light BASI-ALA-PDT. All biopsies were stained for markers of epidermal atypia and
      Langerhans cells (LCs); and at 24 hours to detect oxidative DNA damage. RESULTS:
      Patients had an 81% reduction in AKs and slight improvement in clinical and
      histologic signs of photoaging after 1 month. The biopsied chronically
      photodamaged skin without clinically detectable AKs showed no effect of PDT on
      the LC number, distribution, or morphology; and no oxidative DNA damage, in
      contrast to the changes reported after customary red light PDT. CONCLUSION:
      Customary blue light BASI-ALA-PDT does not affect the LC number or produce
      oxidative DNA damage, the sequelae of red light PDT responsible for
      immunosuppression in treated skin.

PMID- 25072127
TI  - Mitotic rate for thin melanomas: should a single mitotic figure warrant a
      sentinel lymph node biopsy?
AB  - BACKGROUND: The seventh edition of the American Joint Committee on Cancer
      guidelines recognize mitotic rate (MR) as a component of the staging criteria for
      cutaneous melanomas with a Breslow depth <=1 mm. OBJECTIVE: This review discusses
      the evidence behind the threshold of 1 mitosis per square millimeter as a
      prognostic variable in thin melanomas, particularly because it relates to the
      decision to pursue a sentinel lymph node biopsy (SLNB). MATERIALS AND METHODS: We
      performed a systematic review using the PubMed database to identify articles that
      contain prognostic information for thin melanomas based on MR and sentinel lymph
      node (SLN) status. RESULTS: Although the threshold of a single mitosis correlates
      with a statistically significant decrease in survival rates for patients with
      thin melanomas, the clinical relevance remains questionable particularly because
      it relates to the decision to pursue an SLNB. CONCLUSION: A single mitosis in
      thin melanomas does not increase the risk of a positive SLN so much that SLN
      biopsy should be routinely performed for this cohort.

PMID- 25072128
TI  - Single occurrence of intraictal cessation during index course of
      electroconvulsive therapy.
AB  - Intraictal cessation is an intriguing and infrequent phenomenon of uncertain
      clinical or electrophysiological significance that presents in clinical practice
      of ECT. We present a clinical image of one such isolated phenomenon on a person
      with treatment refractory psychosis treated with ECT. 

PMID- 25072129
TI  - The correlation between renal function and bone mineral density.
AB  - AIM: The moderate, severe chronic kidney disease (CKD) and end stage renal
      disease (ESRD) are well-recognized risk factors of bone loss. However, it is
      uncertain whether mild CKD stage affects bone mineral density (BMD). The
      objective of this study is to investigate whether mild and/or more severe
      reduction of GFR is associated with BMD decreasing. METHODS: Between April and
      November 2011, 305 patients were included in this study. Estimated glomerular
      filtration rate (GFR) was calculated by Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equation. According to the GFR, we divided the
      participants into 3 groups: CKD stage I, stage II and stage >=III. BMD was
      compared between different groups. RESULTS: Eighty-one women and 65 men were
      enrolled in the final study. The average age was 65.6. According to the eGFR, 54
      (37.0%), 70 (47.9%) and 22 (15.1%) participants were classified into CKD stage I,
      II and >=III, respectively. The mean T-score was -1.351+/-1.879.A significant
      bone loss was found in the stage >=III group, especially in women (P<0.05). BMD
      decreasing was found significantly in male participants with CKD stage II
      (P=0.041). CONCLUSION: BMD significantly decreased in men with mild renal
      dysfunction. A significant BMD decreasing was also found in the group of CKD
      stage >=III, especially in women. We suggest osteoporosis screening is necessary
      in patients with poor renal function.

PMID- 25072130
TI  - Oncologic outcomes of laparoscopic nephroureterectomy for pT3 upper urinary tract
      urothelial carcinoma.
AB  - AIM: We present the oncologic outcomes of laparoscopic nephroureterectomy
      management of pT3 upper urinary tract urothelial carcinoma. METHODS: Between
      October 2003 and January 2011, 50 patients with pT3 upper urinary tract
      urothelial carcinoma which had pathologically confirmed underwent laparoscopic
      nephroureterectomy at our institution. Demographic data, perioperative results,
      pathological findings and oncologic outcomes were reviewed and analyzed
      retrospectively. RESULTS: There were 36 patients (72%) of high grade lesion and
      14 patients (28%) of low grade lesion. Lymphovascular invasion was observed in 16
      patients (32%) and the surgical margin was positive in one patient. N stage was
      pN0 in 16 (32%), pN1 in 3 (6%), pN2 in 1 (2%) and pN3 in 1 (2%). The 5-year
      overall survival rate was 52.6% and the 5-year cancer-specific survival rate was
      65.3%. Overall recurrence developed in 23 patients. There were 10 patients (20%)
      of urothelial recurrence which were all occurred in the bladder at the mean
      period of 13.6 months, and 7 patients of them were invasive bladder cancer. There
      were 16 patients (32%) of non-urothelial recurrence developed at the mean period
      of 9.69 months. On multivariate analyses lymphadenopathy and lymph node
      involvement of cancer (N+) were identified as independent predictive factors for
      the cancer-specific survival, and concomitant bladder tumor, grade and
      lymphovascular invasion were identified as independent predictive factors for the
      overall recurrence free survival. CONCLUSION: Laparoscopic nephroureterectomy in
      patients with high stage upper urinary tract urothelial carcinoma appear
      comparable to those of open surgery in the regard of oncologic outcomes.

PMID- 25072131
TI  - Efficacy of tension-free vaginal tape obturator and single-incision tension-free
      vaginal tape-Secur, hammock approach, in the treatment of stress urinary
      incontinence.
AB  - AIM: Aim of the present study was to compare the efficacy of tension-free vaginal
      tape obturator and single-incision tension-free transvaginal tape Secur, hammock
      approach, in the treatment of stress urinary incontinence. METHODS: Clinical data
      of patients who received anti-incontinence surgery between June 2008 and July
      2012 were retrospectively analyzed. Efficacy and early failure rate of the
      tension-free vaginal tape obturator and tension-free vaginal tape-Secur hammock
      approach were assessed by cough test and criteria of International Consultation
      on Incontinence Questionnaire-Short Form. Intraoperative and postoperative
      complications were also computed. RESULTS: There were 28 patients in the tension
      free vaginal tape obturator group while 32 patients in the tension-free vaginal
      tape-Secur group. The mean operation time, intraoperative blood loss and
      inpatient days after surgery between the two groups showed no significant
      difference. The catheter retention time of the tension-free vaginal tape
      obturator group was longer than in the tension-free vaginal tape-Secur group. The
      cure rate of the tension-free vaginal tape obturator and tension-free vaginal
      tape-Secur groups were respectively 84% and 80%, and the recurrence rates were
      14.3% and 16.7%, without significant difference. The scores of International
      Consultation on Incontinence Questionnaire-Short Form in two groups both
      decreased after surgery, but there was no difference between the two groups.
      There were no serious complications in the two groups. CONCLUSION: Our study
      demonstrated that both tension-free vaginal tape obturator and tension-free
      vaginal tape-Secur can achieve a cure rate over 80% while with little
      complications, showing both methods are reliable to treat stress urinary
      incontinence.

PMID- 25072132
TI  - Innovations of surgical techniques for the management of inferior vena cava tumor
      thrombus of renal cell carcinoma.
AB  - Surgery for renal cell carcinoma with inferior vena cava thrombus is challenging.
      Cardiopulmonary bypass and deep hypothermic circulatory arrest significantly
      decreased the morbidity and mortality but associated with considerable
      postoperative complications. Debates still exist in one- or two-stage operations
      on which of the cardiac and urologic parts should be performed first. Modified
      maneuvers with main pulmonary artery clamping, vena cystoscope, transesophageal
      echocardiographic incorporation, and inferior vena cava interruptions are good
      for reduced perioperative morbidities. Surgical innovations have greatly
      facilitated the resection of renal cell carcinoma and inferior vena cava
      involvement. The advantages have been remarkable in less trauma, more cosmetic
      advantages, shorter hospital stay, and quicker recovery over the conventional
      open surgery with or without the use of bypass techniques. Such procedures have
      brought about improved long-term survivals. However, novel minimally invasive
      techniques such as robotic-assisted and hybrid approaches remain to gain further
      popularity in larger patient population. This article aims at a collection of the
      innovations of the surgical techniques in relation to the management of inferior
      vena cava tumor thrombus. 

PMID- 25072133
TI  - Granulomatous prostatitis: a rare diagnosis of prostatic disease.

PMID- 25072134
TI  - Solid-solid grinding/templating route to magnetically separable nitrogen-doped
      mesoporous carbon for the removal of Cu(2+) ions.
AB  - N-doped ordered mesoporous carbon materials (NOMC) with 2D hexagonal symmetry
      structure were synthesized via a facile solid-solid grinding/templating route, in
      which the ionic liquids (ILs) of 1-cyanoethyl-3-methylimidazolium chloride and
      SBA-15 were employed as the precursor and hard template, respectively. The as
      synthesized NOMC features with a uniform mesoporous size (3.5nm), ropes-like
      morphology (0.4-1MUm in length) and high surface area (803m(2)/g). The
      quantitative analysis revealed the nitrogen content on the surface of NOMC is
      5.5at%. Magnetic iron nanoparticles were successfully embedded into the carbon
      matrix by introducing iron chloride to the mixture of SBA-15 and ILs during the
      synthesis process. The NOMC-Fe composite possessed superior adsorption capacity
      of Cu(2+) ions (23.6mg/g). Kinetic and isothermal analysis demonstrated the
      strong interactions between Cu(2+) ion and the adsorbent. Furthermore, the
      composite was magnetically separable from solution under an external magnetic
      field and thus displayed a superior reusability in the recycling test. 

PMID- 25072135
TI  - Investigation on mercury removal method from flue gas in the presence of sulfur
      dioxide.
AB  - A new integrated process was developed for the removal and reclamation of mercury
      from the flue gas in the presence of SO2, typically derived from nonferrous metal
      smelting. The new process contains a pre-desulfurization unit (Stage I) and a co
      absorption unit (Stage II). In Stage I, 90% of the SO2 from flue gas can be
      efficiently absorbed by ferric sulfate and reclaimed sulfuric acid. Meanwhile,
      the proportion of Hg(2+) and Hg(0) in the flue gas can be redistributed in this
      stage. Then, over 95% of the Hg(0) and the residual SO2 can be removed
      simultaneously with a composite absorption solution from the flue gas in Stage
      II, which is much more efficient for the Hg(0) reclaiming than the traditional
      method. The composite absorption solution in Stage II, which is composed of
      0.1g/L HgSO4, 1.0% H2O2 and H2SO4, could effectively remove and reclaim Hg(0)
      overcoming the negative effect of SO2 on Hg(0) absorption. Moreover, the
      concentrations of HgSO4 and H2O2 were adjusted with the changes in of the
      concentrations of Hg(0) and SO2 in the flue gas. It is a potential and promising
      technology for the mercury removal and reclaim from the flue gas in the presence
      of SO2. 

PMID- 25072136
TI  - Oxidation of benzothiophene, dibenzothiophene, and methyl-dibenzothiophene by
      ferrate(VI).
AB  - The reduction of sulfur content in liquid fuel is of a high concern
      environmentally, and oxydesulfurization approaches have shown high efficiency for
      removing thiophene-containing compounds from the liquid fuels. The present paper
      investigates the oxidation of benzothiophene (BT), dibenzothiophene (DBT), and 4
      methyl-dibenzothiophene (4-MDBT) by ferrate(VI). The effects of reaction
      conditions such as the reaction medium pH, solvent type, and adsorbent on the
      reactivity of ferrate(VI) with the thiophene-containing compounds were
      investigated. The oxidation of DBT in phosphate-acetonitrile medium was found to
      be highly sensitive toward the reaction pH, and the highest removal efficiency
      was observed at the pH 8.0. The complete conversion of BT and DBT to their
      corresponding sulfones by ferrate(VI) was achieved at room temperature and
      [ferrate(VI)]/[BT/DBT]~7.5 while this molar ratio was found to be ~8.5 for 4
      MDBT. The addition of silica gel during the reaction was applied to enhance the
      oxidation of DBT by ferrate(VI). 

PMID- 25072137
TI  - New approach to solar photo-Fenton operation. Raceway ponds as tertiary treatment
      technology.
AB  - The photo-Fenton process has proven its efficiency in the removal of
      micropollutants. However, the high costs usually associated with it prevent a
      spread of this technology. An important factor affecting costs is the kind of
      photoreactor used, usually tubular with a reflecting surface. Tubular reactors
      like compound parabolic collectors, CPCs, involve high capital costs. In
      comparison, the application of less costly reactors such as the extensive raceway
      ponds (RPRs) would help to spread the use of the photo-Fenton process as tertiary
      treatment at commercial scale. As far as the authors know, RPRs have never been
      used in advanced oxidation processes (AOPs) applications. This work is aimed at
      studying the applicability of RPRs to remove micropollutants with solar photo
      Fenton. For this purpose, a pesticide mixture of commercial acetamiprid (ACTM)
      and thiabendazole (TBZ) (100MUg/L each) was used in simulated secondary effluent.
      Iron concentration (1, 5.5 and 10mg/L) and liquid depth (5, 10 and 15cm) were
      studied as process variables. TBZ was removed at the beginning of the treatment
      (less than 5min), although ACTM removal times were longer (20-40min for the
      highest iron concentrations). High treatment capacity per surface area was
      obtained (48mg/hm(2) with 5.5mg Fe/L and 15cm liquid depth), proving the
      feasibility of using RPRs for micropollutant removal. 

PMID- 25072138
TI  - Unveiling formation mechanism of carcinogenic N-nitrosodimethylamine in ozonation
      of dimethylamine: a density functional theoretical investigation.
AB  - Recent studies found that ozonation of organic pollutants with dimethylamino
      groups produces N-nitrosodimethylamine (NDMA) that is highly carcinogenic to
      humans. However, the formation mechanism of NDMA remains inexplicit, and
      previously proposed mechanisms are inconsistent with experimental observations.
      In this study, the formation mechanism of NDMA in ozonation was explored by
      density functional theory (DFT) calculations, with dimethylamine (DMA) as a model
      compound. By calculating Gibbs energies and energy barriers, formation of NDMA in
      ozonation of DMA was observed to proceed through a hydroxylamine mechanism. The
      calculation results show that hydroxylamine is generated through DMA reacting
      with hydroxyl radicals (HO*) formed from hydrolysis of ozone. DMA reacting with
      hydroxylamine can produce unsymmetrical dimethylhydrazine (UDMH), a well-known
      NDMA precursor. Transformation of UDMH to NDMA is mainly induced by ozone or HO*
      rather than dissolved oxygen proposed previously. The reaction of DMA and
      hydroxylamine is pH dependent, with energy barriers increasing from neutral pH to
      the second pKa of hydroxylamine and then decreasing. This is in accordance with
      the experimentally observed pH dependence of NDMA yield in ozonation, indicating
      that the hydroxylamine mechanism is responsible for the NDMA formation in
      ozonation. 

PMID- 25072139
TI  - Acetaldehyde removal using an atmospheric non-thermal plasma combined with a
      packed bed: role of the adsorption process.
AB  - This work is an attempt in order to help towards understanding the influence of
      the adsorption process on the removal of a VOC (acetaldehyde, CH3CHO) using
      cyclic non thermal plasma (NTP) combined with a packed-bed of a catalyst support,
      alpha-Al2O3. In the first part, the results obtained by placing the saturated
      alumina pellets inside the plasma discharge zone are discussed, in terms of
      acetaldehyde removal, CO and CO2 production. In the second part, adsorption of
      CH3CHO, CO, CO2 and O3 was carried out, from single and multicomponent mixtures
      of the different compounds. The results showed that (i) the adsorption capacities
      followed the order CH3CHO?  CO2>CO; (ii) O3 was decomposed on the alumina
      surface; (iii) CO oxidation occurred on the surface when O3 was present. In the
      third part, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS)
      was used to follow the alumina surface during acetaldehyde adsorption. DRIFTS
      measurements demonstrated that besides the bands of molecularly adsorbed
      acetaldehyde, several absorptions appeared on the spectra showing the
      intermediate surface transformation of acetaldehyde already at 300K. Finally, the
      relationship between the adsorption results and the NTP combined with a packed
      bed process is discussed. 

PMID- 25072140
TI  - Blue marble health: a call for papers.

PMID- 25072141
TI  - Inhibitor-induced conformational stabilization and structural alteration of a mip
      like peptidyl prolyl cis-trans isomerase and its C-terminal domain.
AB  - FKBP22, an Escherichia coli-encoded PPIase (peptidyl-prolyl cis-trans isomerase)
      enzyme, shares substantial identity with the Mip-like pathogenic factors, caries
      two domains, exists as a dimer in solution and binds some immunosuppressive drugs
      (such as FK506 and rapamycin) using its C-terminal domain (CTD). To understand
      the effects of these drugs on the structure and stability of the Mip-like
      proteins, rFKBP22 (a chimeric FKBP22) and CTD+ (a CTD variant) have been studied
      in the presence and absence of rapamycin using different probes. We demonstrated
      that rapamycin binding causes minor structural alterations of rFKBP22 and CTD+.
      Both the proteins (equilibrated with rapamycin) were unfolded via the formation
      of intermediates in the presence of urea. Further study revealed that thermal
      unfolding of both rFKBP22 and rapamycin-saturated rFKBP22 occurred by a three
      state mechanism with the synthesis of intermediates. Intermediate from the
      rapamycin-equilibrated rFKBP22 was formed at a comparatively higher temperature.
      All intermediates carried substantial extents of secondary and tertiary
      structures. Intermediate resulted from the thermal unfolding of rFKBP22 existed
      as the dimers in solution, carried an increased extent of hydrophobic surface and
      possessed relatively higher rapamycin binding activity. Despite the formation of
      intermediates, both the thermal and urea-induced unfolding reactions were
      reversible in nature. Unfolding studies also indicated the considerable
      stabilization of both proteins by rapamycin binding. The data suggest that
      rFKBP22 or CTD+ could be exploited to screen the rapamycin-like inhibitors in the
      future. 

PMID- 25072143
TI  - Oxidative stress of alternariol in Caco-2 cells.
AB  - Alternariol (AOH) is a mycotoxin produced by fungus Alternaria. It is found in a
      wide variety of fruits and cereals products. AOH is able to damage human health.
      The aim of this study was to evaluate the cytotoxicity of AOH in human colon
      adenocarcinoma (Caco-2) cells. Moreover, some events related to oxidative stress
      were evaluated: reactive oxygen species (ROS) generated by oxidation of 2',7'
      dichlorodihydrofluorescein diacetate; peroxidation of lipid (LPO) by
      malondialdehyde (MDA) production; and antioxidant enzymatic capability of
      catalase (CAT) and superoxide dismutase (SOD). Cytotoxicity of AOH (from 3.125 to
      100 MUM) was determined during 24, 48 and 72 h of exposure by different
      endpoints. AOH decreased cell viability by MTT, NR and PC assays. However, no
      IC50 values were obtained by any of the assays tested. AOH induced a strong
      oxidative stress in Caco-2 cells by generation of ROS production and LPO
      associated with a rise in the SOD activity at all concentration tested. ROS
      increased 1.2-fold with respect to the control and MDA production ranged from
      130% to 250% compared to control. Our results demonstrated that in spite of AOH
      showing cytotoxic effect on Caco-2 cells at the highest concentration tested,
      oxidative stress by LPO and ROS was observed at all concentrations assayed. This
      could cause an injury and be hazardous to health.

PMID- 25072142
TI  - Defining the factors that contribute to on-target specificity of antisense
      oligonucleotides.
AB  - To better understand the factors that influence the activity and specificity of
      antisense oligonucleotides (ASOs), we designed a minigene encoding superoxide
      dismutase 1 (SOD-1) and cloned the minigene into vectors for T7 transcription of
      pre-mRNA and splicing in a nuclear extract or for stable integration in cells. We
      designed a series of ASOs that covered the entire mRNA and determined the binding
      affinities and activities of the ASOs in a cell-free system and in cells. The
      mRNA bound known RNA-binding proteins on predicted binding sites in the mRNA. The
      higher order structure of the mRNA had a significantly greater effect than the
      RNA-binding proteins on ASO binding affinities as the ASO activities in cells and
      in the cell-free systems were consistent. We identified several ASOs that
      exhibited off-target hybridization to the SOD-1 minigene mRNA in the cell-free
      system. Off-target hybridization occurred only at highly accessible unstructured
      sites in the mRNA and these interactions were inhibited by both the higher order
      structure of the mRNA and by RNA-binding proteins. The same off-target
      hybridization interactions were identified in cells that overexpress E. coli
      RNase H1. No off-target activity was observed for cells expressing only
      endogenous human RNase H1. Neither were these off-target heteroduplexes
      substrates for recombinant human RNase H1 under multiple-turnover kinetics
      suggesting that the endogenous enzyme functions under similar kinetic parameters
      in cells and in the cell-free system. These results provide a blueprint for
      design of more potent and more specific ASOs. 

PMID- 25072144
TI  - Assessment of long-term health risks after accidental exposure using haemoglobin
      adducts of epichlorohydrin.
AB  - On September 9th, 2002, two goods trains collided in Bad Munder, Lower Saxony,
      causing the release of more than 40 metric tonnes of epichlorohydrin (1-chloro
      2,3-epoxypropane) into the environment. A human biomonitoring study was performed
      to evaluate the accidental exposure to epichlorohydrin and to assess the possible
      long-term, i.e. carcinogenic health effects. This was done on the basis of a
      biochemical effect monitoring using the N-(3-chloro-2-hydroxypropyl)valine and
      the N-(2,3-dihydroxypropyl)valine haemoglobin adducts of epichlorohydrin in blood
      to respond to missing ambient monitoring immediately after the crash. N-(3-chloro
      2-hydroxypropyl)valine adduct levels above the LOQ (25 pmol/g globin) ranged from
      32.0 to 116.4 pmol/g globin in 6 out of 628 samples. The N-(2,3
      dihydroxypropyl)valine adduct was not detected above the LOD (10 pmol/g globin)
      in any of the blood samples. Based on the quantified N-(3-chloro-2
      hydroxypropyl)valine adduct values, the body doses after two days of exposure
      were estimated to be in the range of 1.7-6.2 nmol/kg body weight. The reverse
      estimation of the external exposure leads to cumulative additional lifetime
      cancer risks ranging from 2.61*10(-8) to 9.48*10(-8). The estimated excess
      lifetime cancer risks have to be assessed as extremely low. Our biomonitoring
      study facilitated the dialogue between individuals and groups concerned and
      authorities, because suspected or occurred exposures and risks to human health
      could be quantified and interpreted in a sound manner.

PMID- 25072146
TI  - Significance of hypoxia in the physiological function of intervertebral disc
      cells.
AB  - The intervertebral disc (IVD) is the largest avascular structure in the body, and
      IVD cells reside in vivo in an environment that is considered to be hypoxic.
      However, the role of oxygen in IVD cell biology remains an issue of debate. By
      reviewing the available literature about the effect of oxygen tension on
      regulating the phenotype, energy metabolism, matrix production, and survival of
      IVD cells, as well as on the expression and function of hypoxia-inducible factor
      in IVD cells, we conclude that hypoxia is essential in maintaining the
      physiological function of IVD cells. Modulating the oxygen tension of the IVD or
      the activity of hypoxia-inducible factor in IVD cells may be a promising strategy
      for the prevention and treatment of IVD degeneration. 

PMID- 25072145
TI  - ALDOB acts as a novel HBsAg-binding protein and its coexistence inhibits
      cisplatin-induced HepG2 cell apoptosis.
AB  - Chronic infection with hepatitis B virus is a cause of end-stage liver disease
      and hepatocellular carcinoma (HCC). We previously screened fructose-bisphosphate
      aldolase B (ALDOB) as a candidate binding protein of hepatitis B surface antigen
      (HBsAg) using a yeast 2-hybrid assay. In this study we aimed to confirm ALDOB as
      a binding protein of the S region of the HbsAg (HBs) and to investigate the
      function and involved mechanism between its interactions during HCC development.
      Our results demonstrated that both of exogenous and endogenous ALDOB proteins
      bind to HBs and colocalize in the cytoplasm in vitro. The coexistence of HBs and
      ALDOB inhibit apoptosis of cisplatin-induced HepG2 cells. Furthermore, western
      blot analysis showed the coexistence of HBs and ALDOB enhance the
      phosphorylations of AKT and its downstream of GSK-3beta (phosphorylation);
      decreased expression of the pro-apoptotic proteins Bax, Bid, Bim, and Puma; and
      increased expression of the prosurvival proteins Bcl-2, Bcl-xl, and Mcl-1 in
      HepG2 cells. These findings suggest that interaction between HBs and ALDOB might
      be applied as a potential therapeutic target during the treatment of HBV-related
      hepatitis or HCC.

PMID- 25072147
TI  - Determining Omics spatiotemporal dimensions using exciting new nanoscopy
      techniques to assess complex cell responses to DNA damage: part A--radiomics.
AB  - Recent ground-breaking developments in Omics have generated new hope for
      overcoming the complexity and variability of biological systems while
      simultaneously shedding more light on fundamental radiobiological questions that
      have remained unanswered for decades. In the era of Omics, our knowledge of how
      genes and proteins interact in the frame of complex networks to preserve genome
      integrity has been rapidly expanding. Nevertheless, these functional networks
      must be observed with strong correspondence to the cell nucleus, which is the
      main target of ionizing radiation. Nuclear architecture and nuclear processes,
      including DNA damage responses, are precisely organized in space and time.
      Information regarding these intricate processes cannot be achieved using high
      throughput Omics approaches alone, but requires sophisticated structural probing
      and imaging. Based on the results obtained from studying the relationship between
      higher-order chromatin structure, DNA double-strand break induction and repair,
      and the formation of chromosomal translocations, we show the development of Omics
      solutions especially for radiation research (radiomics) (discussed in this
      article) and how confocal microscopy as well as novel approaches of molecular
      localization nanoscopy fill the gaps to successfully place the Omics data in the
      context of space and time (discussed in our other article in this issue,
      "Determining Omics Spatiotemporal Dimensions Using Exciting New Nanoscopy
      Techniques to Assess Complex Cell Responses to DNA Damage: Part B-
      Structuromics"). Finally, we introduce a novel method of specific chromatin
      nanotargeting and speculate future perspectives, which may combine nanoprobing
      and structural nanoscopy to observe structure-function correlations in living
      cells in real time. Thus, the Omics networks obtained from function analyses may
      be enriched by real-time visualization of Structuromics.

PMID- 25072148
TI  - Determining Omics spatiotemporal dimensions using exciting new nanoscopy
      techniques to assess complex cell responses to DNA damage: part B--structuromics.
AB  - Recent groundbreaking developments in Omics and bioinformatics have generated new
      hope for overcoming the complexity and variability of (radio)biological systems
      while simultaneously shedding more light on fundamental radiobiological questions
      that have remained unanswered for decades. In the era of Omics, our knowledge of
      how genes and dozens of proteins interact in the frame of complex signaling and
      repair pathways (or, rather, networks) to preserve the integrity of the genome
      has been rapidly expanding. Nevertheless, these functional networks must be
      observed with strong correspondence to the cell nucleus, which is the main target
      of ionizing radiation. Information regarding these intricate processes cannot be
      achieved using high-throughput Omics approaches alone; it requires sophisticated
      structural probing and imaging. In the first part of this review, the article
      "Giving Omics Spatiotemporal Dimensions Using Exciting New Nanoscopy Techniques
      to Assess Complex Cell Responses to DNA Damage: Part A--Radiomics," we showed the
      development of different Omics solutions and how they are contributing to a
      better understanding of cellular radiation response. In this Part B we show how
      high-resolution confocal microscopy as well as novel approaches of molecular
      localization nanoscopy fill the gaps to successfully place Omics data in the
      context of space and time. The dynamics of double-strand breaks during repair
      processes and chromosomal rearrangements at the microscale correlated to
      aberration induction are explained. For the first time we visualize pan-nuclear
      nucleosomal rearrangements and clustering at the nanoscale during repair
      processes. Finally, we introduce a novel method of specific chromatin
      nanotargeting based on a computer database search of uniquely binding
      oligonucleotide combinations (COMBO-FISH). With these challenging techniques on
      hand, we speculate future perspectives that may combine specific COMBO-FISH
      nanoprobing and structural nanoscopy to observe structure-function correlations
      in living cells in real-time. Thus, the Omics networks obtained from function
      analyses may be enriched by real-time visualization of Structuromics.

PMID- 25072149
TI  - Acupuncture, connective tissue, and peripheral sensory modulation.
AB  - Although considerable controversy surrounds the legitimacy of acupuncture as a
      treatment, a growing literature on the physiological effects of acupuncture
      needling in animals and humans is providing new insights into basic cellular
      mechanisms including connective tissue mechanotransduction and purinergic
      signaling. This review summarizes these findings and proposes a model combining
      connective tissue plasticity and peripheral sensory modulation in response to the
      sustained stretching of tissue that results from acupuncture needle manipulation.

PMID- 25072150
TI  - Cytoskeleton dynamics in the retina.
AB  - BACKGROUND: Cytoskeleton is one of the essential forms of protein, important in
      the existence of both eukaryotic as well as prokaryotic cells. Its transformation
      plays a vital role in cell division and intracellular transportation by
      facilitating intracellular vesicular traffic. Among the various tissue types in
      the body, the neural tissue exhibits the maximum heterogeneity, and hence the
      role of cytoskeleton at both developmental and functional levels becomes
      paramount. Cytoskeleton dynamics have been established in the neural physiology,
      but only at the level of axonal development and growth. Retina has not been
      adequately studied in the context of cytoskeletal proteins. METHODS: We reviewed
      the last 10 years of literature with reference to the development, growth,
      degeneration, and regeneration of the retina and the role of cytoskeleton in each
      aspect. We have focused on various changes that the retina undergoes at the
      cytosolic and cytoskeletal levels in the course of degeneration as well as
      regeneration. FINDINGS: For this review, we compiled research articles pertaining
      to the role of cytoskeletal and other associated proteins involved in development
      of retina, which used various animal models. The effect of SNPs in the
      cytoskeletal proteins and their impact in retinal degeneration is also discussed.
      CONCLUSION: Studies describing the role of cytoskeleton in the anatomy and
      physiology of retina and its layers, although they are few, collectively provide
      an opportunity to understand retinal development in the context of cytoskeleton
      dynamics.

PMID- 25072151
TI  - Mycobacterium biofilms: factors involved in development, dispersal, and
      therapeutic strategies against biofilm-relevant pathogens.
AB  - Many bacteria can develop biofilm (BF), a multicellular structure largely
      combining bacteria and their extracellular polymeric substances (EPS). The
      formation of biofilm results in an alternative existence in which microbes ensure
      their survival in adverse environments. Biofilm-relevant infections are more
      persistent, resistant to most antibiotics, and more recalcitrant to host
      immunity. Mycobacterium tuberculosis, the causative agent of tuberculosis, can
      develop biofilm, though whether M. tuberculosis can form biofilm within
      tuberculosis patients has yet to be determined. Here, we summarize the factors
      involved in the development and dispersal of mycobacterial biofilms, as well as
      underlying regulatory factors and inhibitors against biofilm to deepen our
      understanding of their development and to elucidate potential novel modes of
      action for future antibiotics. Key factors in biofilm formation identified as
      drug targets represent a novel and promising avenue for developing better
      antibiotics. 

PMID- 25072152
TI  - Astaxanthin alleviates early brain injury following subarachnoid hemorrhage in
      rats: possible involvement of Akt/bad signaling.
AB  - Apoptosis has been proven to play a crucial role in early brain injury
      pathogenesis and to represent a target for the treatment of subarachnoid
      hemorrhage (SAH). Previously, we demonstrated that astaxanthin (ATX)
      administration markedly reduced neuronal apoptosis in the early period after SAH.
      However, the underlying molecular mechanisms remain obscure. In the present
      study, we tried to investigate whether ATX administration is associated with the
      phosphatidylinositol 3-kinase-Akt (PI3K/Akt) pathway, which can play an important
      role in the signaling of apoptosis. Our results showed that post-SAH treatment
      with ATX could cause a significant increase of phosphorylated Akt and Bad levels,
      along with a significant decrease of cleaved caspase-3 levels in the cortex after
      SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also
      significantly reduce secondary brain injury characterized by neurological
      dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the
      PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX
      in the early period after SAH by downregulating ATX-induced activation of Akt/Bad
      and upregulating cleaved caspase-3 levels. These results provided the evidence
      that ATX could attenuate apoptosis in a rat SAH model, potentially, in part,
      through modulating the Akt/Bad pathway. 

PMID- 25072155
TI  - Associations of HLA-A, -B and -DRB1 types with oral diseases in Swiss adults.
AB  - Human leukocyte antigens (HLA) are crucial components of host defense against
      microbial challenge but the associations of HLA types with oral infectious
      diseases have not been studied in detail. This prospective cross-sectional study
      examined associations of HLA-A, -B and -DRB1 types with common oral diseases in a
      healthy Swiss adult population. 257 subjects (107 m, 150 f, mean age: 43.5 yr;
      range: 21-58 yr) with known HLA-A, -B and -DRB1 profiles and comprehensive
      medical records were included. A thorough anamnesis was followed by oral
      examinations including saliva flow measurements, the DMFT score for cariological
      status, complete periodontal status with plaque and bleeding indexes as well as
      assessment of mucosal alterations and temporomandibular dysfunction (TMD).
      Student's t-test and Pearson chi-square test were utilized to compare the oral
      diseases between HLA positive and negative subjects. Bonferroni correction for
      multiple comparisons was used and PBonf<0.05 was considered statistically
      significant. HLA types -B15 (PBonf = 0.002), -B51 (PBonf = 0.02) and -DRB1*12
      (PBonf = 0.02) were associated with less periodontal disease manifestations. HLA
      A32 had a positive association with TMD dysfunction (PBonf = 0.012). No other
      statistically significant associations were observed. In conclusion, HLA types
      may contribute to the development of oral diseases in generally healthy Caucasian
      adults. 

PMID- 25072153
TI  - Predictive usefulness of urinary biomarkers for the identification of
      cyclosporine A-induced nephrotoxicity in a rat model.
AB  - The main side effect of cyclosporine A (CsA), a widely used immunosuppressive
      drug, is nephrotoxicity. Early detection of CsA-induced acute nephrotoxicity is
      essential for stop or minimize kidney injury, and timely detection of chronic
      nephrotoxicity is critical for halting the drug and preventing irreversible
      kidney injury. This study aimed to identify urinary biomarkers for the detection
      of CsA-induced nephrotoxicity. We allocated salt-depleted rats to receive CsA or
      vehicle for 7, 14 or 21 days and evaluated renal function and hemodynamics,
      microalbuminuria, renal macrophage infiltration, tubulointerstitial fibrosis and
      renal tissue and urinary biomarkers for kidney injury. Kidney injury molecule-1
      (KIM-1), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6),
      fibronectin, neutrophil gelatinase-associated lipocalin (NGAL), TGF-beta,
      osteopontin, and podocin were assessed in urine. TNF-alpha, IL-6, fibronectin,
      osteopontin, TGF-beta, collagen IV, alpha smooth muscle actin (alpha -SMA) and
      vimentin were assessed in renal tissue. CsA caused early functional renal
      dysfunction and microalbuminuria, followed by macrophage infiltration and late
      tubulointerstitial fibrosis. Urinary TNF-alpha, KIM-1 and fibronectin increased
      in the early phase, and urinary TGF-beta and osteopontin increased in the late
      phase of CsA nephrotoxicity. Urinary biomarkers correlated consistently with
      renal tissue cytokine expression. In conclusion, early increases in urinary KIM
      1, TNF-alpha, and fibronectin and elevated microalbuminuria indicate acute CsA
      nephrotoxicity. Late increases in urinary osteopontin and TGF-beta indicate
      chronic CsA nephrotoxicity. These urinary kidney injury biomarkers correlated
      well with the renal tissue expression of injury markers and with the temporal
      development of CsA nephrotoxicity. 

PMID- 25072156
TI  - Transcriptome analysis of Catharanthus roseus for gene discovery and expression
      profiling.
AB  - The medicinal plant, Catharanthus roseus, accumulates wide range of terpenoid
      indole alkaloids, which are well documented therapeutic agents. In this study,
      deep transcriptome sequencing of C. roseus was carried out to identify the
      pathways and enzymes (genes) involved in biosynthesis of these compounds. About
      343 million reads were generated from different tissues (leaf, flower and root)
      of C. roseus using Illumina platform. Optimization of de novo assembly involving
      a two-step process resulted in a total of 59,220 unique transcripts with an
      average length of 1284 bp. Comprehensive functional annotation and gene ontology
      (GO) analysis revealed the representation of many genes involved in different
      biological processes and molecular functions. In total, 65% of C. roseus
      transcripts showed homology with sequences available in various public
      repositories, while remaining 35% unigenes may be considered as C. roseus
      specific. In silico analysis revealed presence of 11,620 genic simple sequence
      repeats (excluding mono-nucleotide repeats) and 1820 transcription factor
      encoding genes in C. roseus transcriptome. Expression analysis showed roots and
      leaves to be actively participating in bisindole alkaloid production with clear
      indication that enzymes involved in pathway of vindoline and vinblastine
      biosynthesis are restricted to aerial tissues. Such large-scale transcriptome
      study provides a rich source for understanding plant-specialized metabolism, and
      is expected to promote research towards production of plant-derived
      pharmaceuticals. 

PMID- 25072158
TI  - Is bladder tumor location associated with prostate cancer detection after
      intravesical bacillus Calmette-Guerin instillation?
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of bladder tumor
      (BT) location on prostate cancer (PCa) detection in patients with elevated PSA
      levels after intravesical BCG instillation. METHODS: Between February 2004 and
      January 2013 prostate biopsies were performed in 59 non-muscle invasive bladder
      cancer (NMIBC) patients whose PSA level were elevated (>=3 ng/ml) after a 6 week
      course of intravesical BCG (Oncotice, 12.5 mg in 50 ml normal saline).
      Differences in PCa detection according to the BT location [bladder neck and/or
      trigone (Group 1, n = 22) vs. other locations (Group 2, n = 37)] were evaluated.
      The Fisher's exact test and the Mann-Whitney U test were used to evaluate the
      association between categorical and continuous variables, respectively. RESULTS:
      A total of 14 patients (23.7%) were diagnosed with PCa. The mean +/- standard
      deviation (SD) PSA before intravesical BCG instillation and prostate biopsy were
      1.36+/-1.04 ng/ml in Group 1 and 1.09+/-1.12 ng/ml in Group 2 (P = 0.633), and
      6.05+/-3.57 ng/ml in Group 1 and 5.13+/-3.88 ng/ml in Group 2 (P = 0.378),
      respectively. Interestingly, whereas PCa was detected upon biopsy in only one
      patient in Group 1 (4.5%), 13 cases were detected in Group 2 (35.1%) (P = 0.009).
      CONCLUSIONS: PCa detection after intravesical BCG was highly associated with BT
      location. Prostate biopsy should therefore be considered when PSA level is
      elevated after BCG instillation and his BT is located far from the bladder neck.

PMID- 25072157
TI  - A time course analysis of the electrophysiological properties of neurons
      differentiated from human induced pluripotent stem cells (iPSCs).
AB  - Many protocols have been designed to differentiate human embryonic stem cells
      (ESCs) and human induced pluripotent stem cells (iPSCs) into neurons. Despite the
      relevance of electrophysiological properties for proper neuronal function, little
      is known about the evolution over time of important neuronal electrophysiological
      parameters in iPSC-derived neurons. Yet, understanding the development of basic
      electrophysiological characteristics of iPSC-derived neurons is critical for
      evaluating their usefulness in basic and translational research. Therefore, we
      analyzed the basic electrophysiological parameters of forebrain neurons
      differentiated from human iPSCs, from day 31 to day 55 after the initiation of
      neuronal differentiation. We assayed the developmental progression of various
      properties, including resting membrane potential, action potential, sodium and
      potassium channel currents, somatic calcium transients and synaptic activity.
      During the maturation of iPSC-derived neurons, the resting membrane potential
      became more negative, the expression of voltage-gated sodium channels increased,
      the membrane became capable of generating action potentials following adequate
      depolarization and, at day 48-55, 50% of the cells were capable of firing action
      potentials in response to a prolonged depolarizing current step, of which 30%
      produced multiple action potentials. The percentage of cells exhibiting miniature
      excitatory post-synaptic currents increased over time with a significant increase
      in their frequency and amplitude. These changes were associated with an increase
      of Ca2+ transient frequency. Co-culturing iPSC-derived neurons with mouse glial
      cells enhanced the development of electrophysiological parameters as compared to
      pure iPSC-derived neuronal cultures. This study demonstrates the importance of
      properly evaluating the electrophysiological status of the newly generated
      neurons when using stem cell technology, as electrophysiological properties of
      iPSC-derived neurons mature over time. 

PMID- 25072161
TI  - Pharmacophore modeling, 3D-QSAR and molecular docking studies of benzimidazole
      derivatives as potential FXR agonists.
AB  - Farnesoid X receptor (FXR) is a potential therapeutic target for the treatment of
      diabetes mellitus. Atom-based three-dimensional quantitative structure activity
      relationship (3D-QSAR) models were developed for a series of 48 benzimidazole
      based agonists of FXR. A total of five pharmacophore hypotheses were generated
      based on the survival score to build QSAR models. HHHRR was considered as a best
      model that consisted of three hydrophobic features (H) and two aromatic rings
      (R). The best hypothesis, HHHRR yielded a 3D-QSAR model with good statistical
      value (R(2)) of 0.8974 for a training set of 39 compounds and also showed good
      predictive power with correlation coefficient (Q(2)) of 0.7559 for a test set of
      nine compounds. Furthermore, molecular docking simulation was performed to
      understand the binding affinity of 48 benzimidazole-based compounds against the
      active site of human FXR protein. Docking results revealed that both the most
      active and least active compounds showed similar binding mode to the
      experimentally observed binding mode of co-crystallized ligand. The generated 3D
      contour maps revealed the structure activity relationship of the compounds.
      Substitution effects at different positions of benzimidazole derivatives would
      lead to the discovery of new agonists against human FXR protein.

PMID- 25072160
TI  - The role of environmental factors in the spatial distribution of Japanese
      encephalitis in mainland China.
AB  - Japanese encephalitis (JE) is the most common cause of viral encephalitis and an
      important public health concern in the Asia-Pacific region, particularly in China
      where 50% of global cases are notified. To explore the association between
      environmental factors and human JE cases and identify the high risk areas for JE
      transmission in China, we used annual notified data on JE cases at the center of
      administrative township and environmental variables with a pixel resolution of 1
      km*1 km from 2005 to 2011 to construct models using ecological niche modeling
      (ENM) approaches based on maximum entropy. These models were then validated by
      overlaying reported human JE case localities from 2006 to 2012 onto each
      prediction map. ENMs had good discriminatory ability with the area under the
      curve (AUC) of the receiver operating curve (ROC) of 0.82-0.91, and low extrinsic
      omission rate of 5.44-7.42%. Resulting maps showed JE being presented extensively
      throughout southwestern and central China, with local spatial variations in
      probability influenced by minimum temperatures, human population density, mean
      temperatures, and elevation, with contribution of 17.94%-38.37%, 15.47%-21.82%,
      3.86%-21.22%, and 12.05%-16.02%, respectively. Approximately 60% of JE cases
      occurred in predicted high risk areas, which covered less than 6% of areas in
      mainland China. Our findings will help inform optimal geographical allocation of
      the limited resources available for JE prevention and control in China, find
      hidden high-risk areas, and increase the effectiveness of public health
      interventions against JE transmission.

PMID- 25072163
TI  - Metal-templated chiral Bronsted base organocatalysis.
AB  - Inert octahedral chiral-at-metal complexes are an emerging class of asymmetric
      catalysts that exploit the globular, rigid nature and stereochemical options of
      octahedral compounds. While the central transition metal serves as a structural
      anchorpoint and provides metal centrochirality, catalysis is mediated through the
      organic ligand sphere, thereby merging the branches of transition metal catalysis
      and organocatalysis. Here we report the development of inert octahedral 3
      aminopyrazolato iridium(III) complexes as novel chiral Bronsted base catalysts
      and demonstrate their merit with applications to highly effective asymmetric
      sulfa-Michael and aza-Henry reactions, permitting catalyst loadings down to 0.02
      and 0.25 mol%, respectively. The observed high stereocontrol can be rationalized
      by a bifunctional mode of action in which the iridium catalyst, after the initial
      proton transfer, controls a ternary complex through defined hydrogen bonding
      interactions. This work reveals the potential of octahedral metal complexes as
      chiral scaffolds for the design of high-performance asymmetric catalysts. 

PMID- 25072162
TI  - Implicit processing of visual emotions is affected by sound-induced affective
      states and individual affective traits.
AB  - The ability to recognize emotions contained in facial expressions are affected by
      both affective traits and states and varies widely between individuals. While
      affective traits are stable in time, affective states can be regulated more
      rapidly by environmental stimuli, such as music, that indirectly modulate the
      brain state. Here, we tested whether a relaxing or irritating sound environment
      affects implicit processing of facial expressions. Moreover, we investigated
      whether and how individual traits of anxiety and emotional control interact with
      this process. 32 healthy subjects performed an implicit emotion processing task
      (presented to subjects as a gender discrimination task) while the sound
      environment was defined either by a) a therapeutic music sequence (MusiCure), b)
      a noise sequence or c) silence. Individual changes in mood were sampled before
      and after the task by a computerized questionnaire. Additionally, emotional
      control and trait anxiety were assessed in a separate session by paper and pencil
      questionnaires. Results showed a better mood after the MusiCure condition
      compared with the other experimental conditions and faster responses to happy
      faces during MusiCure compared with angry faces during Noise. Moreover,
      individuals with higher trait anxiety were faster in performing the implicit
      emotion processing task during MusiCure compared with Silence. These findings
      suggest that sound-induced affective states are associated with differential
      responses to angry and happy emotional faces at an implicit stage of processing,
      and that a relaxing sound environment facilitates the implicit emotional
      processing in anxious individuals. 

PMID- 25072164
TI  - Pre-clinical in vitro and in vivo safety evaluation of bovine whey derived
      osteopontin, Lacprodan(r) OPN-10.
AB  - Lacprodan(r) OPN-10 is a proprietary whey-based protein product that contains
      bovine-derived osteopontin (OPN), found in human milk and other bodily tissues.
      In vitro genotoxicity tests conducted according to accepted guidelines at up to
      5000MUg/plate OPN failed to induce genetic mutations in Salmonella typhimurium
      strains and Escherichia coli strain and did not induce chromosomal aberrations or
      cytotoxicity in human lymphocytes. Administration of an acute dose of
      Lacprodan(r) OPN-10 (2300mg/kg body weight) to male and female mice did not
      induce chromosomal damage or mitotic apparatus damage to erythroblasts from bone
      marrow. Lacprodan(r) OPN-10 was evaluated in a 13-week oral toxicity study in
      which rats were fed diets containing 0.5%, 1.0% and 2.0% Lacprodan(r) OPN-10. No
      test-article-related clinical observations or toxicological effects on body or
      organ weights, food consumption, ophthalmic effects, locomotor activity,
      hematology, clinical chemistry, urinalysis, or pathology were identified. In a
      teratogenicity study, administration of Lacprodan(r) OPN-10 up to 2500mg/kgbw/day
      via gavage to pregnant rats had no effect on dams or pups. The No Observed
      Adverse Effect Level (NOAEL) for Lacprodan(r) OPN-10 in the 13-week toxicity
      study was 2.0% of the diet (equivalent to 1208mg/kgbw/day in male rats and
      1272mg/kgbw/day in female rats). 

PMID- 25072165
TI  - Impact of smoking on estrogenic efficacy.
AB  - Depending on the type, duration and intensity of cigarette smoking, the efficacy
      of endogenous and exogenous estrogen can be reduced or completely cancelled. Not
      only does smoking diminish the beneficial effects of estrogen on hot flushes and
      urogenital symptoms and its positive effects on lipid metabolism, but smoking
      also can reduce estrogen's ability to prevent osteoporosis and perhaps also
      cardiovascular diseases. This is mainly caused by dose-dependent elevated hepatic
      clearance, partially in conjunction with lower estrogen levels, and has been
      demonstrated so far only with oral estrogen applications. Compensation for the
      failure of therapeutic action should not be made by increasing the dose in
      smokers since this might result in the production of potentially mutagenic
      estrogen metabolites associated with a higher risk of breast cancer. Since the
      favorable effects of estrogens seem to be not lost in smokers when estrogens are
      applied transdermally, this route should be preferred in smokers. The most
      important conclusion from the data presented is that the effects of smoking are
      very complex and dependent on a multiplicity of factors, so that different types
      of clinically relevant negative effects must be expected. Women who continue to
      smoke despite all warnings should be informed that smoking, in addition to all
      its other negative effects, can also jeopardize the success of hormone
      replacement therapy.

PMID- 25072166
TI  - Clinician-teacher: Doffing two hats for the sake of one.

PMID- 25072167
TI  - Hierarchical virtual screening approaches in small molecule drug discovery.
AB  - Virtual screening has played a significant role in the discovery of small
      molecule inhibitors of therapeutic targets in last two decades. Various ligand
      and structure-based virtual screening approaches are employed to identify small
      molecule ligands for proteins of interest. These approaches are often combined in
      either hierarchical or parallel manner to take advantage of the strength and
      avoid the limitations associated with individual methods. Hierarchical
      combination of ligand and structure-based virtual screening approaches has
      received noteworthy success in numerous drug discovery campaigns. In hierarchical
      virtual screening, several filters using ligand and structure-based approaches
      are sequentially applied to reduce a large screening library to a number small
      enough for experimental testing. In this review, we focus on different
      hierarchical virtual screening strategies and their application in the discovery
      of small molecule modulators of important drug targets. Several virtual screening
      studies are discussed to demonstrate the successful application of hierarchical
      virtual screening in small molecule drug discovery. 

PMID- 25072168
TI  - Estimating the composition of species in metagenomes by clustering of next
      generation read sequences.
AB  - Faster and cheaper sequencing technologies together with the ability to sequence
      uncultured microbes collected from any environment present us an opportunity to
      distill meaningful information from the millions of new genomic sequences from
      environmental samples, called metagenome. Contrary to conventional cultured
      microbes, however, the metagenomic data is extremely heterogeneous and noisy.
      Therefore the separation of the sets of sequenced genomic fragments that belong
      to different microbes is essential for successful assembly of microbial genomes.
      In this paper, we present a novel clustering method for a given metagenomic
      dataset. The metagenomic dataset has some distinguished features because (i) it
      is possible that similar sequence patterns may exist in different species and
      (ii) each species has different number of individuals in the given metagenomic
      dataset. Our method overcomes these obstacles by using the Gaussian mixture model
      and analysis of mixture profiles, and taking advantage of genomic signatures
      extracted from the metagenomic dataset. Unlike conventional clustering methods
      where clusters are discovered through global similarities of data instances, our
      method builds clusters by combining the data instances sharing local similarities
      captured by mixture analysis. By considering shared mixture components, our
      method is able to create clusters of genomic sequences although they are globally
      distinct each other. We applied our method to an artificial metagenomic dataset
      comprised of simulated 47 million reads from 25 real microbial genomes, and
      analyzed the resulting clusters in terms of the number of clusters, the number of
      participating species and dominant species in each cluster. Even though our
      approach cannot address all challenges in the field of metagenome sequence
      clustering, we believe that out method can contribute to take a step forward to
      achieve the goals. 

PMID- 25072169
TI  - 1,1-Olefin-bridged bis-(2-indenyl) metallocenes of titanium and zirconium.
AB  - Tetrasubstituted alkenes bearing geminal 2-indenyl substituents--9-[bis(1H-inden
      2-yl)methylidene]-9H-fluorene (6), 2,2'-(2,2-diphenylethene-1,1-diyl)-bis(1H
      indene) (7), and 2,2'-(2-propylpent-1-ene-1,1-diyl)-bis(1H-indene) (8) have been
      synthesized and metallated to form a new class of ansa titanium and zirconium
      metallocene complexes containing a single sp(2)-hybridized carbon bridge. The
      synthesis of the tetramethylated bis-indenyl Zr-analog is described. In addition,
      the 1,1-bis-indenyl ethylene is prepared and the Zr complex is modified by olefin
      metathesis. X-ray structure analyses reveal strained eta(5) sandwich complexes
      with highly open metal centers. These complexes have proven active in the
      polymerization of ethylene and its copolymerization with 1-hexene.

PMID- 25072171
TI  - Observation of a quantum Cheshire Cat in a matter-wave interferometer experiment.
AB  - From its very beginning, quantum theory has been revealing extraordinary and
      counter-intuitive phenomena, such as wave-particle duality, Schrodinger cats and
      quantum non-locality. Another paradoxical phenomenon found within the framework
      of quantum mechanics is the 'quantum Cheshire Cat': if a quantum system is
      subject to a certain pre- and postselection, it can behave as if a particle and
      its property are spatially separated. It has been suggested to employ weak
      measurements in order to explore the Cheshire Cat's nature. Here we report an
      experiment in which we send neutrons through a perfect silicon crystal
      interferometer and perform weak measurements to probe the location of the
      particle and its magnetic moment. The experimental results suggest that the
      system behaves as if the neutrons go through one beam path, while their magnetic
      moment travels along the other. 

PMID- 25072172
TI  - How do undergraduate medical students perceive social accountability?
AB  - AIM: The concept of social accountability within undergraduate training is
      embedded within the remit of medical schools. Little is known of how medical
      students perceive social accountability, recognize aspects of their training
      contributing to the development of this concept and cultivate the underpinning
      values. METHODS: Students nearing graduation were recruited to participate in
      focus groups designed to explore their perceptions of social accountability,
      which curricular aspects had contributed to their understanding, and to
      investigate the implications of individual variations in training. RESULTS:
      Students expressed limited appreciation of the concept of social accountability
      and acknowledged little explicit teaching around underpinning core concepts such
      as awareness of local health needs, advocacy and nurturing of altruism. However,
      participants recognized numerous aspects of the course and learning initiatives
      as impacting on their attitudes towards this concept implicitly. CONCLUSION: This
      study highlights areas of their undergraduate training that students recognize as
      having the greatest impact on their development into socially accountable
      professionals. It poses some significant challenges for health care educators in
      addressing unintended consequences, including an outcome-driven educational
      approach, in reducing students' capacity or willingness to engage in curricular
      challenges often designed to embed this concept.

PMID- 25072173
TI  - Development of the CASH assessment tool to address existential concerns in
      patients with serious illness.
AB  - INTRODUCTION: Existential suffering in patients with serious illness
      significantly impacts quality of life, yet it remains a challenge to define,
      assess, and manage adequately. Improving upon understanding and practice in the
      existential domain is a topic of interest for palliative care providers. METHODS:
      As a quality improvement project, our palliative care team created an existential
      assessment tool utilizing a dialogue-oriented approach with four questions
      designed to identify sources of existential distress as well as strengths and
      challenges in coping with this distress. The tool utilized the mnemonic CASH,
      with each letter representing the core objective of the question. Providers who
      requested the palliative care consult were asked to evaluate the CASH assessment.
      On completion of the project, palliative care consultants evaluated the
      appropriateness of the CASH assessment tool. RESULTS: Patient responses to the
      CASH questions were insightful and reflected their beliefs, priorities, and
      concerns. Eight of nine providers found that the assessment enabled understanding
      of their patient. Seven noted a positive impact on their practice, and five
      reported an improvement in patient care after the assessment. The palliative care
      consultants who used the tool enjoyed using it, and half of them suggested
      changes to patient care based on their assessment. The most common reasons for
      not using the CASH assessment were inappropriateness to the consult, lack of
      perceived patient/caregiver receptiveness, or consultation service too busy.
      CONCLUSION: Our quality improvement project demonstrated that the CASH assessment
      tool is useful in ascertaining existential concerns of patients with serious
      illness. It enhances patient care by the primary team as well as the palliative
      care team. As a brief set of questions with an easy-to-remember mnemonic, the
      CASH assessment tool is feasible for a busy palliative consult service.
      Furthermore, the positive results of this project merit more rigorous evaluation
      of the CASH assessment tool in the future.

PMID- 25072175
TI  - Secretin-stimulated MRCP to optimally select patients for pancreatic endotherapy?

PMID- 25072176
TI  - Hippo/YAP, beta-catenin, and the cancer cell: a "menage a trois" in
      hepatoblastoma.

PMID- 25072177
TI  - The cost of a loaf of bread in symptomless celiac disease.

PMID- 25072178
TI  - Mortality after bladder augmentation in children with spina bifida.
AB  - PURPOSE: Renal failure has been a leading cause of death for children with spina
      bifida. Although improvements in management have increased survival, current data
      on mortality are sparse. Bladder augmentation, a modern intervention to preserve
      renal function, carries risks of morbidity and mortality. We determined long-term
      mortality and causes of death in patients with spina bifida treated with bladder
      augmentation. MATERIALS AND METHODS: We retrospectively reviewed the records of
      patients with spina bifida who underwent bladder augmentation between 1979 and
      2013. Those born before 1972 or older than 21 years at augmentation were
      excluded. Demographic and surgical data were collected. Outcomes were obtained
      from medical records, death records and the Social Security Death Index. Fisher
      exact and Wilcoxon rank-sum tests and Kaplan-Meier plots were used for analysis.
      RESULTS: Of 888 patients in our bladder reconstruction database 369 with spina
      bifida met inclusion criteria. Median followup was 10.8 years. A total of 28
      deaths (7.6%) occurred. The leading causes of mortality were nonurological
      infections (ventriculoperitoneal shunt related, decubitus ulcer fasciitis, etc)
      and pulmonary disease. Two patients (0.5%) died of renal failure. No patient died
      of malignancy or bladder perforation. Patients with a ventriculoperitoneal shunt
      had a higher mortality rate than those without a shunt (8.9% vs 1.5%, p = 0.04).
      CONCLUSIONS: Previously reported mortality rates of 50% to 60% in patients with
      spina bifida do not appear to apply in children who have undergone bladder
      augmentation. On long-term followup leading causes of death in patients with
      spina bifida after bladder augmentation were nonurological infections rather than
      complications associated with augmentation or renal failure.

PMID- 25072179
TI  - Biofeedback for nonneuropathic daytime voiding disorders in children: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - PURPOSE: Biofeedback has been used to treat children with symptoms of bladder
      dysfunction not responding to standard therapy alone. However, evidence of the
      effectiveness of biofeedback is scarce and is based on small studies. We
      conducted a systematic review of the literature to assess the effects of
      biofeedback as adjunctive therapy for symptoms of nonneuropathic voiding
      disorders in children up to age 18 years. MATERIALS AND METHODS: We searched
      MEDLINE((r)), Embase((r)) and CENTRAL on the OvidSP((r)) platform as well as
      conference proceedings for randomized trials presented at scientific conventions,
      symposia and workshops through August 13, 2013. Hand searches and review of
      reference lists of retrieved articles were also performed. RESULTS: Five eligible
      studies were included in the systematic review, of which 4 (382 participants)
      were pooled in the meta-analysis based on available outcomes data. The overall
      proportion of cases with resolved incontinence at month 6 was similar in the
      biofeedback and control groups (OR 1.37 [95% CI 0.64 to 2.93], RD 0.07 [-0.09,
      0.23]). There was also no significant difference in mean maximum urinary flow
      rate (mean difference 0.50 ml, range -0.56 to 1.55) or likelihood of urinary
      tract infection (OR 1.30 [95% CI 0.65 to 2.58]). CONCLUSIONS: Current evidence
      does not support the effectiveness of biofeedback in the management of children
      with nonneuropathic voiding disorders. More high quality, randomized controlled
      trials are needed to better evaluate the effect of biofeedback.

PMID- 25072180
TI  - High regional variation in urethroplasty in the United States.
AB  - PURPOSE: We identified clinical and regional factors associated with the use of
      urethroplasty vs repeat endoscopic management for urethral stricture disease.
      MATERIALS AND METHODS: We analyzed claims for patients 18 to 65 years old in the
      2007 to 2011 MarketScan(r) Commercial Claims and Encounters Database with a
      diagnosis of urethral stricture. The primary outcome was treatment with
      urethroplasty vs repeat endoscopic management, defined as more than 2 dilations
      or direct vision internal urethrotomies. The likelihood of urethroplasty vs
      repeat endoscopic management was determined for each major metropolitan area in
      the United States. Multivariate logistic regression was done to identify factors
      associated with urethroplasty. RESULTS: We identified 41,056 patients with
      urethral stricture, yielding a diagnosis rate of 296/100,000 men in MarketScan.
      Repeat endoscopic management and urethroplasty were performed in 2,700 and 1,444
      patients, respectively. Compared to patients treated with repeat endoscopic
      management those with urethroplasty were younger (median age 44 vs 54 years) and
      more likely to have a Charlson comorbidity score of 0 (84% vs 77%), have traveled
      out of a metropolitan area for care (34% vs 17%) and have a reconstructive
      urologist in the treatment metropolitan area (76% and 62%, each p <0.001). When
      controlling for age and Charlson comorbidity score, travel out of a metropolitan
      area (OR 2.7, 95% CI 2.2-3.3) and a reconstructive urologist in the treatment
      metropolitan area (OR 2.0, 95% CI 1.7-2.5) were associated with a greater
      likelihood of urethroplasty vs repeat endoscopic management. CONCLUSIONS: Despite
      the well established benefits of urethroplasty compared to repeat endoscopic
      management a strong bias for repeat endoscopic management exists in many regions
      in the United States.

PMID- 25072181
TI  - New modalities for evaluation and surveillance of complex renal cysts.
AB  - PURPOSE: The increased use of abdominal imaging has led to more frequent
      detection of incidental renal cysts. Since the inception of the Bosniak
      classification system, management of Bosniak I, III and IV cysts has been clearly
      defined, while evaluation and management of Bosniak II and IIF cysts have
      remained a clinical dilemma. Discussions of new imaging modalities are becoming
      increasingly prevalent in the radiological literature. In this context we
      performed a comprehensive review of the recent literature on complex renal cysts
      focusing on new imaging modalities, surveillance strategies and biopsy. MATERIALS
      AND METHODS: We performed a comprehensive literature review of articles published
      from January 1, 1998 through December 31, 2013 via MEDLINE((r)), EMBASE and the
      Cochrane Collection using a predetermined search strategy. All studies included
      were performed in humans older than 18 years, were written in English and had an
      abstract available for review. We grouped studies into 1 of 5 categories, ie
      computerized tomography, magnetic resonance imaging, ultrasound, biopsy and
      surveillance. RESULTS: While computerized tomography and magnetic resonance
      imaging with and without contrast enhancement remain the gold standard to
      evaluate cystic lesions of the kidney, diffusion-weighted magnetic resonance
      imaging and contrast enhanced ultrasound have surfaced as new tools for
      assessment of complex cysts. Comparative effectiveness studies on these new
      imaging modalities are limited. Image guided biopsy has increasingly been shown
      to be useful for evaluation of intermediate (Bosniak II and IIF) complex cysts.
      We found few studies providing guidance on the duration and/or intensity of
      surveillance required for intermediate complex renal cysts. CONCLUSIONS: Although
      new and enhanced techniques are in development and may be useful in the future
      management of complex renal cysts, there is a paucity of data regarding the value
      of these new techniques. Future research should focus on surveillance of
      intermediate complex renal cysts, particularly on the ideal frequency and type of
      imaging required.

PMID- 25072183
TI  - [Turf toe injury--extension sprain of the first metatarsophalangeal joint].
AB  - Injuries of the first metatarsophalangeal (1MTP) joint in the performance of
      sports are normally rare. The term turf toe injury designates a sprain of the
      first metatarsophalangeal (1MTP) joint. The trauma mechanism describes a
      hyperextension in contrast to a "sand-toe"-injury which is caused by a
      hyperflexion. Injuries to the metatarsophalangeal (MTP) joint of the great toe
      have increased in incidence over the last years following the introduction of
      synthetic surfaces and the establish use of lighter footwear. Although most
      common in American football players, similar injuries can also be found in
      sporting activities like basketball, soccer, gymnastics or dance. The trauma
      mechanism leads to varying degrees of sprain or disruption of the supporting soft
      tissue structures. Furthermore damage to the articular cartilage and adjacent
      bone can be detected. An assessment of the extent of soft-tissue disruption or
      even damage of the cartilage is essential in treatment planning. The conservative
      treatment methods including relative rest, shoe modification, and insoles are in
      most cases successful. But in case of an advanced stage or failure of
      conservative treatment, surgical treatment is mostly necessary. The turf toe
      injury must be diagnosed early and evaluated properly. The injury leads to a loss
      in sports time and competition and can progress to chronic osteoarthritis of the
      first metatarsal joint. 

PMID- 25072182
TI  - Preoperatively misclassified, surgically removed benign renal masses: a
      systematic review of surgical series and United States population level burden
      estimate.
AB  - PURPOSE: A significant proportion of renal masses removed for suspected
      malignancy are histologically benign with the probability inversely proportional
      to lesion size. To our knowledge the number of preoperatively misclassified
      benign renal masses treated with nephrectomy is currently unknown. Given the
      increasing incidence and decreasing average size of renal cell carcinoma, this
      burden is likely increasing. We estimated the population level burden of
      surgically removed, preoperatively misclassified benign renal masses in the
      United States. MATERIALS AND METHODS: We systematically reviewed the literature
      for studies of pathological findings of renal masses removed for suspected renal
      cell carcinoma based on preoperative imaging through July 1, 2014. We excluded
      studies that did not describe benign pathology and with masses not stratified by
      size, and in which pathology results were based on biopsy. SEER data were queried
      for the incidence of surgically removed renal cell carcinomas in 2000 to 2009.
      RESULTS: A total of 19 studies of tumor pathology based on size met criteria for
      review. Pooled estimates of the proportion of benign histology in our primary
      analysis (American studies only and 1 cm increments) were 40.4%, 20.9%, 19.6%,
      17.2%, 9.2% and 6.4% for tumors less than 1, 1 to less than 2, 2 to less than 3,
      3 to less than 4, 4 to 7 and greater than 7, respectively. The estimated number
      of surgically resected benign renal masses in the United States from 2000 to 2009
      increased by 82% from 3,098 to 5,624. CONCLUSIONS: These estimates suggest that
      the population level burden of preoperatively misclassified benign renal masses
      is substantial and increasing rapidly, paralleling increases in surgically
      resected small renal cell carcinoma. This study illustrates an important and to
      our knowledge previously unstudied dimension of overtreatment that is not
      directly quantified in contemporary surveillance data.

PMID- 25072184
TI  - Cognitive processing of visual images in migraine populations in between headache
      attacks.
AB  - BACKGROUND AND OBJECTIVE: People with migraine headache have altered interictal
      visual sensory-level processing in between headache attacks. Here we examined the
      extent to which these migraine abnormalities may extend into higher visual
      processing such as implicit evaluative analysis of visual images in between
      migraine events. METHODS: Specifically, we asked two groups of participants-
      migraineurs (N=29) and non-migraine controls (N=29)--to view a set of unfamiliar
      commercial logos in the context of a target identification task as the brain
      electrical responses to these objects were recorded via event-related potentials
      (ERPs). Following this task, participants individually identified those logos
      that they most liked or disliked. We applied a between-groups comparison of how
      ERP responses to logos varied as a function of hedonic evaluation. RESULTS: Our
      results suggest migraineurs have abnormal implicit evaluative processing of
      visual stimuli. Specifically, migraineurs lacked a bias for disliked logos found
      in control subjects, as measured via a late positive potential (LPP) ERP
      component. CONCLUSIONS: These results suggest post-sensory consequences of
      migraine in between headache events, specifically abnormal cognitive evaluative
      processing with a lack of normal categorical hedonic evaluation.

PMID- 25072185
TI  - Distribution and phenotype of TrkB oligodendrocyte lineage cells in the adult rat
      spinal cord.
AB  - The distribution and phenotype of a previously undescribed population of
      nonneuronal cells in the intact spinal cord that expresses TrkB, the cognate
      receptor for brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4),
      were characterized by examining the extent of co-localization of TrkB with NG2,
      which identifies oligodendrocyte progenitors (OPCs) or CC1, a marker for mature
      oligodendrocytes (OLs). All TrkB nonneuronal cells expressed Olig2, confirming
      their role in the OL lineage. Similar to OPCs and OLs, TrkB cells resided in gray
      and white matter of the spinal cord in similar abundance. Less than 2% of TrkB
      cells expressed NG2, while over 80% of TrkB cells in the adult spinal cord co
      expressed CC1. Most OPCs did not express detectable levels of TrkB, however a
      small OPC pool (~5%) showed TrkB immunoreactivity. The majority of mature OLs
      (~65%) expressed TrkB, but a population of mature OLs (~36%) did not express TrkB
      at detectable levels, and 17% of TrkB nonneuronal cells did not express NG2 or
      CC1. Approximately 20% of the TrkB nonneuronal population in the ventral horn
      resided in close proximity to motor neurons and were categorized as perineuronal.
      We conclude that TrkB is expressed by several pools of OL lineage cells in the
      adult spinal cord. These findings are important in understanding the neurotrophin
      regulation of OL lineage cells in the adult spinal cord. 

PMID- 25072187
TI  - Pulmonary embolism and renal vein thrombosis in patients with nephrotic syndrome:
      prospective evaluation of prevalence and risk factors with CT.
AB  - PURPOSE: To prospectively determine the prevalence of pulmonary embolism ( PE
      pulmonary embolism ) and renal vein thrombosis ( RVT renal vein thrombosis ) with
      computed tomography (CT) and to identify markers predictive of PE pulmonary
      embolism and/or RVT renal vein thrombosis in a large consecutive cohort of
      patients with nephrotic syndrome. MATERIALS AND METHODS: This study was approved
      by the local institutional review board, and all patients or their guardians
      provided written informed consent. Consecutive patients with nephrotic syndrome
      (24-hour urine protein > 3.5 g) underwent combined CT pulmonary angiography for
      PE pulmonary embolism and renal CT venography for RVT renal vein thrombosis .
      Prevalence of PE pulmonary embolism and/or RVT renal vein thrombosis was
      estimated for different ages, sexes, and histopathologic types of nephrotic
      syndrome. Multivariate analysis was used to determine independent predictors for
      PE pulmonary embolism and/or RVT renal vein thrombosis in patients with nephrotic
      syndrome. RESULTS: There were 512 patients in the study cohort (331 male
      patients, 181 female patients; mean age, 37 years +/- 17 [standard deviation];
      range, 9-81 years), including 80 children. One hundred eighty (35%) of 512
      patients had PE pulmonary embolism and/or RVT renal vein thrombosis , with PE
      pulmonary embolism the more common condition (85% [153 of 180]). PE pulmonary
      embolism was associated with RVT renal vein thrombosis in 85 (56%) of 153
      patients and was isolated in 68 patients (44%). Most patients with PE pulmonary
      embolism (84% [128 of 153]) were asymptomatic. One hundred twelve (22%) of 505
      patients had RVT renal vein thrombosis . PE pulmonary embolism and/or RVT renal
      vein thrombosis was found in 15 (19%) of 80 children with nephrotic syndrome,
      while 165 (38%) of 432 adult patients with nephrotic syndrome had PE pulmonary
      embolism and/or RVT renal vein thrombosis (P = .001). Membranous nephropathy was
      the most common histopathologic type associated with PE pulmonary embolism and/or
      RVT renal vein thrombosis (48% [88 of 183]). Membranous nephropathy, age greater
      than 60 years, high hemoglobin level, long prothrombin time, and high creatinine
      level were independent predictors of PE pulmonary embolism and/or RVT renal vein
      thrombosis (P < .05 for all). CONCLUSION: PE pulmonary embolism and RVT renal
      vein thrombosis are common in patients with nephrotic syndrome. PE pulmonary
      embolism is more common than RVT renal vein thrombosis , is most often
      asymptomatic, and is most frequently found in patients with membranous
      nephropathy. A high index of suspicion and a low threshold for diagnostic work-up
      is warranted in these patients.

PMID- 25072188
TI  - Sodium uptake in cell construction and subsequent in operando electrode behaviour
      of Prussian blue analogues, Fe[Fe(CN)6](1-x).yH2O and FeCo(CN)6.
AB  - The development of electrodes for ambient temperature sodium-ion batteries
      requires the study of new materials and the understanding of how crystal
      structure influences properties. In this study, we investigate where sodium
      locates in two Prussian blue analogues, Fe[Fe(CN)6]1-x.yH2O and FeCo(CN)6. The
      evolution of the sodium site occupancies, lattice and volume is shown during
      charge-discharge using in situ synchrotron X-ray powder diffraction data. Sodium
      insertion is found to occur in these electrodes during cell construction and
      therefore Fe[Fe(CN)6]1-x.yH2O and FeCo(CN)6 can be used as positive electrodes.
      NazFeFe(CN)6 electrodes feature higher reversible capacities relative to
      NazFeCo(CN)6 electrodes which can be associated with a combination of structural
      factors, for example, a major sodium-containing phase, ~Na0.5FeFe(CN)6 with
      sodium locating either at the x = y = z = 0.25 or x = y = 0.25 and z = 0.227(11)
      sites and an electrochemically inactive sodium-free Fe[Fe(CN)6]1-x.yH2O phase.
      This study demonstrates that key questions about electrode performance and
      attributes in sodium-ion batteries can be addressed using time-resolved in situ
      synchrotron X-ray diffraction studies. 

PMID- 25072186
TI  - Genome-wide analysis of drought induced gene expression changes in flax (Linum
      usitatissimum).
AB  - A robust phenotypic plasticity to ward off adverse environmental conditions
      determines performance and productivity in crop plants. Flax (linseed), is an
      important cash crop produced for natural textile fiber (linen) or oilseed with
      many health promoting products. This crop is prone to drought stress and yield
      losses in many parts of the world. Despite recent advances in drought research in
      a number of important crops, related progress in flax is very limited. Since,
      response of this plant to drought stress has not been addressed at the molecular
      level; we conducted microarray analysis to capture transcriptome associated with
      induced drought in flax. This study identified 183 differentially expressed genes
      (DEGs) associated with diverse cellular, biophysical and metabolic programs in
      flax. The analysis also revealed especially the altered regulation of cellular
      and metabolic pathways governing photosynthesis. Additionally, comparative
      transcriptome analysis identified a plethora of genes that displayed differential
      regulation both spatially and temporally. These results revealed co-regulated
      expression of 26 genes in both shoot and root tissues with implications for
      drought stress response. Furthermore, the data also showed that more genes are
      upregulated in roots compared to shoots, suggesting that roots may play important
      and additional roles in response to drought in flax. With prolonged drought
      treatment, the number of DEGs increased in both tissue types. Differential
      expression of selected genes was confirmed by qRT-PCR, thus supporting the
      suggested functional association of these intrinsic genes in maintaining growth
      and homeostasis in response to imminent drought stress in flax. Together the
      present study has developed foundational and new transcriptome data sets for
      drought stress in flax. 

PMID- 25072189
TI  - The emergence of complex behaviours in molecular magnetic materials.
AB  - Molecular magnetism is considered an area where magnetic phenomena that are
      usually difficult to demonstrate can emerge with particular clarity. Over the
      years, however, less understandable systems have appeared in the literature of
      molecular magnetic materials, in some cases showing features that hint at the
      spontaneous emergence of global structures out of local interactions. This
      ingredient is typical of a wider class of problems, called complex behaviours,
      where the theory of complexity is currently being developed. In this perspective
      we wish to focus our attention on these systems and the underlying problematic
      that they highlight. We particularly highlight the emergence of the signatures of
      complexity in several molecular magnetic systems, which may provide unexplored
      opportunities for physical and chemical investigations. 

PMID- 25072191
TI  - Determination of sample temperature in unstable static fields by combining solid
      state (79)Br and (13)C NMR.
AB  - Monitoring the isotropic chemical shifts to calibrate the sample temperature
      presupposes a perfect stability of the static magnetic field. It can be difficult
      to satisfy this requirement in solid-state NMR measurements. This paper describes
      a simple way to recover the accurate temperature dependence of the (79)Br
      resonance after subtracting changes of resonance frequency due to variations of
      the static field, monitored by the (13)C resonance. 

PMID- 25072192
TI  - Application of binomial-edited CPMG to shale characterization.
AB  - Unconventional shale resources may contain a significant amount of hydrogen in
      organic solids such as kerogen, but it is not possible to directly detect these
      solids with many NMR systems. Binomial-edited pulse sequences capitalize on
      magnetization transfer between solids, semi-solids, and liquids to provide an
      indirect method of detecting solid organic materials in shales. When the organic
      solids can be directly measured, binomial-editing helps distinguish between
      different phases. We applied a binomial-edited CPMG pulse sequence to a range of
      natural and experimentally-altered shale samples. The most substantial signal
      loss is seen in shales rich in organic solids while fluids associated with
      inorganic pores seem essentially unaffected. This suggests that binomial-editing
      is a potential method for determining fluid locations, solid organic content, and
      kerogen-bitumen discrimination. 

PMID- 25072190
TI  - An eight-channel T/R head coil for parallel transmit MRI at 3T using ultra-low
      output impedance amplifiers.
AB  - Parallel transmit is an emerging technology to address the technical challenges
      associated with MR imaging at high field strengths. When developing arrays for
      parallel transmit systems, one of the primary factors to be considered is the
      mechanism to manage coupling and create independently operating channels. Recent
      work has demonstrated the use of amplifiers to provide some or all of the channel
      to-channel isolation, reducing the need for on-coil decoupling networks in a
      manner analogous to the use of isolation preamplifiers with receive coils. This
      paper discusses an eight-channel transmit/receive head array for use with an
      ultra-low output impedance (ULOI) parallel transmit system. The ULOI amplifiers
      eliminated the need for a complex lumped element network to decouple the eight
      rung array. The design and construction details of the array are discussed in
      addition to the measurement considerations required for appropriately
      characterizing an array when using ULOI amplifiers. B1 maps and coupling matrices
      are used to verify the performance of the system. 

PMID- 25072193
TI  - State Opportunities and Strategies for Breastfeeding Promotion Through the
      Affordable Care Act.

PMID- 25072194
TI  - Guillain-Barre and Miller Fisher syndromes--new diagnostic classification.
AB  - Guillain-Barre syndrome (GBS) and its variant, Miller Fisher syndrome (MFS),
      exist as several clinical subtypes with different neurological features and
      presentations. Although the typical clinical features of GBS and MFS are well
      recognized, current classification systems do not comprehensively describe the
      full spectrum of either syndrome. In this Perspectives article, GBS and MFS are
      classified on the basis of current understanding of the common pathophysiological
      profiles of each disease phenotype. GBS is subclassified into classic and
      localized forms (for example, pharyngeal-cervical-brachial weakness and bifacial
      weakness with paraesthesias), and MFS is divided into incomplete (for example,
      acute ophthalmoparesis, acute ataxic neuropathy) and CNS subtypes (Bickerstaff
      brainstem encephalitis). Diagnostic criteria based on clinical characteristics
      are suggested for each condition. We believe this approach to be more inclusive
      than existing systems, and argue that it could facilitate early clinical
      diagnosis and initiation of appropriate immunotherapy. 

PMID- 25072196
TI  - Mucosal immunization: a review of strategies and challenges.
AB  - The vast majority of pathogens enter the human body via the mucosal surfaces of
      the gastrointestinal, respiratory, and urogenital tracts, where they initiate
      mucosal infections that lead to systemic infections. Despite strong evidence that
      a good mucosal immune response can effectively prevent systemic infection too,
      only a few mucosal vaccines are available due to their low efficiency. Most
      current immunization techniques involve systemic injection, but they are
      ineffective to induce immunization at a mucosal site. It is a great challenge to
      target a mucosal compartment that can induce protective immunity at mucosal sites
      as well as systemic sites. A better understanding of cellular and molecular
      factors involved in the regulation of mucosal immunity will aid in the design of
      safer mucosal vaccines that elicit the desired protective immunity against
      infectious diseases such as HIV. The development of mucosal vaccines, whether for
      prevention of infectious diseases or for immunotherapy, requires antigen delivery
      and adjuvant systems that can effectively present vaccine or immunotherapeutic
      antigens to the mucosal sites. In this review, we examine the mechanism of
      mucosal protection, induction of mucosal immune response, types of vaccines,
      current status of marketed vaccines, and novel strategies for protection against
      infections and for treatment of inflammatory disorders. Additionally, we offer
      perspectives on future challenges and research directions. 

PMID- 25072195
TI  - Pain in neuromyelitis optica--prevalence, pathogenesis and therapy.
AB  - Terrible, agonizing, wretched, sickening and unbearable--these are words
      frequently used by patients with neuromyelitis optica (NMO) to describe a very
      common symptom of their disease: pain. More than 80% of patients with NMO
      experience pain from this condition, which severely affects their quality of
      life. At present, there is no known therapy that produces satisfactory relief
      from NMO-associated pain. In fact, contemporary pain therapy is largely
      ineffective in these patients, suggesting that the mechanisms underlying pain in
      NMO differ substantially from those of other treatable causes of pain. Until now,
      the near-complete neglect of research into pain mechanisms in NMO has precluded
      rational pain therapy. In this Perspectives article, expertise from the fields of
      neuroimmunology, neurology and pain research is combined to explore, for the
      first time, the mechanisms underlying pain in patients with NMO, and to identify
      molecular and cellular targets for therapy.

PMID- 25072197
TI  - Small RNAs: the qualified candidates for gene manipulation in diverse clinical
      pathologies.
AB  - In recent years, RNA interference (RNAi) has become a tool of choice to analyze
      and target the in vitro and in vivo function of mammalian genes. RNAi down
      regulates gene expression by inducing enzyme-dependent degradation of targeted
      mRNA. This can be achieved using small double-stranded RNAs (dsRNAs), including
      small interfering RNAs (siRNAs), micro RNAs, and piwi RNAs. These active, small
      dsRNAs can regulate endogenous genes in both somatic and germ cells such that
      they can defend the genome from invasive nucleic acids. Extension of the concept
      of RNAi to preclinical studies indicates its probable application in the
      treatment of cancers, viral infections, arterial stenosis, and genetic disorders.
      Exciting results from ongoing clinical trials have raised the expectations of the
      scientific community for the use of RNAi in "real cures". Rational pharmaceutical
      design of these molecules can further open a Pandora's box of newer therapeutic
      options. However, efficient delivery of these small dsRNAs to target tissues or
      cells and their unanticipated nonspecific effects comprise a few important issues
      that still need to be addressed. In this review, we offer an overview of
      different small dsRNAs, their biogenesis, and their applicability in
      therapeutics. Current delivery strategies and formulation techniques to achieve
      the desired transfection capability and RNAi products in clinical trials are also
      discussed. 

PMID- 25072198
TI  - Ancient and advanced approaches for the treatment of an inflammatory autoimmune
      disease-psoriasis.
AB  - Psoriasis is a chronic, proliferative, and inflammatory skin disease with
      reactive abnormal epidermal differentiation and hyperproliferation that affects 2
      3% of the global population. Various types of psoriasis have been identified by
      clinical outcomes such as skin biopsies and blood analysis: plaque psoriasis,
      flexural psoriasis, guttate psoriasis, pustular psoriasis, psoriatic arthritis,
      scalp psoriasis, nail psoriasis, and erythrodermic psoriasis. The major factors
      which may be considered as causes of psoriasis are bacterial infections or other
      infection triggers, genetics, environment, immune disorders, weather, stress
      triggers, and skin injury. Various ancient approaches such as acupuncture, water
      treatment, and dietary treatment are available to help control psoriasis, but
      they are only able to relieve symptoms. Currently, numerous advanced strategies
      are based on the type of psoriasis, its location, extent, and severity.
      Nanotechnological approaches, biological approaches, photodynamic therapy, and
      PUVA (psoralens + UVA) therapy have been successfully used induce a reduction of
      psoriasis for months to years. These well-tolerated therapies, which have long
      lasting remission and improve quality of life, are effective in 80-85% of
      patients. In this review, we describe different ancient therapies and advanced
      approaches to treating moderate-to-severe psoriasis that are on the market or
      currently in clinical trials. 

PMID- 25072199
TI  - Anthocyanin characterization, total phenolic quantification and antioxidant
      features of some Chilean edible berry extracts.
AB  - The anthocyanin composition and HPLC fingerprints of six small berries endemic of
      the VIII region of Chile were investigated using high resolution mass analysis
      for the first time (HR-ToF-ESI-MS). The antioxidant features of the six endemic
      species were compared, including a variety of blueberries which is one of the
      most commercially significant berry crops in Chile. The anthocyanin fingerprints
      obtained for the fruits were compared and correlated with the antioxidant
      features measured by the bleaching of the DPPH radical, the ferric reducing
      antioxidant power (FRAP), the superoxide anion scavenging activity assay (SA),
      and total content of phenolics, flavonoids and anthocyanins measured by
      spectroscopic methods. Thirty one anthocyanins were identified, and the major
      ones were quantified by HPLC-DAD, mostly branched 3-O-glycosides of delphinidin,
      cyanidin, petunidin, peonidin and malvidin. Three phenolic acids (feruloylquinic
      acid, chlorogenic acid, and neochlorogenic acid) and five flavonols (hyperoside,
      isoquercitrin, quercetin, rutin, myricetin and isorhamnetin) were also
      identified. Calafate fruits showed the highest antioxidant activity (2.33 +/-
      0.21 MUg/mL in the DPPH assay), followed by blueberry (3.32 +/- 0.18 MUg/mL), and
      arrayan (5.88 +/- 0.21), respectively. 

PMID- 25072200
TI  - Triterpenoids from Gymnema sylvestre and their pharmacological activities.
AB  - Because plants are estimated to produce over 200,000 metabolites, research into
      new natural substances that can be used in the pharmaceutical, agrochemical and
      agro-industrial production of drugs, biopesticides and food additives has grown
      in recent years. The global market for plant-derived drugs over the last decade
      has been estimated to be approximately 30.69 billion USD. A relevant specific
      example of a plant that is very interesting for its numerous pharmacological
      properties, which include antidiabetic, anticarcinogenic, and neuroprotective
      effects is Gymnema sylvestre, used as a medicinal plant in Asia for thousands of
      years. Its properties are attributed to triterpenoidic saponins. In light of the
      considerable interest generated in the chemistry and pharmacological properties
      of G. sylvestre triterpenes and their analogues, we have undertaken this review
      in an effort to summarise the available literature on these promising bioactive
      natural products. The review will detail studies on the isolation, chemistry and
      bioactivity of the triterpenoids, which are presented in the tables. In
      particular the triterpenoids oxidised at C-23; their isolation, distribution in
      different parts of the plant, and their NMR spectral data; their names and
      physico-chemical characterisation; and the biological properties associated with
      these compounds, with a focus on their potential chemotherapeutic applications. 

PMID- 25072201
TI  - The validation of an analytical method for sulfentrazone residue determination in
      soil using liquid chromatography and a comparison of chromatographic sensitivity
      to millet as a bioindicator species.
AB  - Commonly used herbicides, such as sulfentrazone, pose the risk of soil
      contamination due to their persistence, bioaccumulation and toxicity.
      Phytoremediation by green manure species has been tested using biomarkers, but
      analytical data are now required to confirm the extraction of sulfentrazone from
      soil. Thus, the present work was carried out to analyze sulfentrazone residues in
      soil based on liquid chromatography with a comparison of these values to the
      sensitivity of the bioindicator Pennisetum glaucum. The soil samples were
      obtained after cultivation of Crotalaria juncea and Canavalia ensiformis at four
      seeding densities and with three doses of sulfentrazone. The seedlings were
      collected into pots, at two different depths, after 75 days of phytoremediator
      sowing and then were used to determine the herbicide persistence in the soil. A
      bioassay with P. glaucum was carried out in the same pot. High-performance liquid
      chromatography (HPLC), using UV-diode array detection (HPLC/UV-DAD), was used to
      determine the herbicide residues. The HPLC determination was optimized and
      validated according to the parameters of precision, accuracy, linearity, limit of
      detection and quantification, robustness and specificity. The bioindicator P.
      glaucum was more sensitive to sulfentrazone than residue determination by HPLC.
      Changes in sulfentrazone concentration caused by green manure phytoremediation
      were accurately identified by the bioindicator. However, a true correlation
      between the size of the species and the analyte content was not identified. 

PMID- 25072202
TI  - Rubus fruticosus L.: constituents, biological activities and health related uses.
AB  - Rubus fruticosus L. is a shrub famous for its fruit called blackberry fruit or
      more commonly blackberry. The fruit has medicinal, cosmetic and nutritive value.
      It is a concentrated source of valuable nutrients, as well as bioactive
      constituents of therapeutic interest highlighting its importance as a functional
      food. Besides use as a fresh fruit, it is also used as ingredient in cooked
      dishes, salads and bakery products like jams, snacks, desserts, and fruit
      preserves. R. fruticosus contains vitamins, steroids and lipids in seed oil and
      minerals, flavonoids, glycosides, terpenes, acids and tannins in aerial parts
      that possess diverse pharmacological activities such as antioxidant, anti
      carcinogenic, anti-inflammatory, antimicrobial anti-diabetic, anti-diarrheal, and
      antiviral. Various agrogeoclimatological factors like cultivar, environmental
      conditions of the area, agronomic practices employed, harvest time, post-harvest
      storage and processing techniques all influence the nutritional composition of
      blackberry fruit. This review focuses on the nutrients and chemical constituents
      as well as medicinal properties of different parts of R. fruticosus. Various
      cultivars and their physicochemical characteristics, polyphenolic content and
      ascorbic acid content are also discussed. The information in the present work
      will serve as baseline data and may lead to new biomedical applications of R.
      fruticosus as functional food. 

PMID- 25072203
TI  - Calculating distortions of short DNA duplexes with base pairing between an
      oxidatively damaged guanine and a guanine.
AB  - DNA is constantly being oxidized, and oxidized DNA is prone to mutation;
      moreover, guanine is highly sensitive to several oxidative stressors. Several
      oxidatively damaged forms of guanine-including 2,2,4-triamino-5(2H)-oxazolone
      (Oz), iminoallantoin (Ia), and spiroiminodihydantoin (Sp)-can be paired with
      guanine, and cause G:C-C:G transversions. Previous findings indicate that guanine
      is incorporated more efficiently opposite Oz than opposite Ia or Sp, and that
      these differences in efficiency cannot be explained by differences in the
      stabilities of G:Oz, G:Ia, and G:Sp base pairs calculated ab initio. Here, to
      explain previous experimental result, we used a 3-base-pair model DNA duplex to
      calculate the difference in the stability and the distortion of DNA containing a
      G:Oz, G:Ia, or G:Sp base pair. We found that the stability of the structure
      containing 5' and 3' base pairs adjacent to G:Oz was more stable than that
      containing the respective base pairs adjacent to G:Ia or G:Sp. Moreover, the
      distortion of the structure in the DNA model duplex that contained a G:Oz was
      smaller than that containing a G:Ia or G:Sp. Therefore, our discussion can
      explain the previous results involving translesion synthesis past an oxidatively
      damaged guanine.

PMID- 25072204
TI  - Light focusing in the Anderson regime.
AB  - Anderson localization is a regime in which diffusion is inhibited and waves (also
      electromagnetic waves) get localized. Here we exploit adaptive optics to achieve
      focusing in disordered optical fibres in the Anderson regime. By wavefront
      shaping and optimization, we observe the generation of a propagation-invariant
      beam, where light is trapped transversally by disorder, and show that Anderson
      localizations can be also excited by extended speckled beams. We demonstrate that
      disordered fibres allow a more efficient focusing action with respect to standard
      fibres in a way independent of their length, because of the propagation-invariant
      features and cooperative action of transverse localizations. 

PMID- 25072205
TI  - Executive functioning and visual working memory.
AB  - The matter of modality is controversially discussed in the context of working
      memory (WM). There is evidence that modality-specific processes are accompanied
      by amodal processes to some extent. We investigated the relationship between
      executive-functioning tasks and visual WM (VWM) and were especially interested in
      the issue of amodal processes. Our correlational analyses suggest modality
      independent relations of the tasks. We also aimed to quantify to what extent
      executive functioning is meaningful for VWM performances. We therefore estimated
      the relationship between executive tasks and VWM performances in a healthy (n =
      710) and a clinical traumatic brain injury sample (n = 151) as well as in the
      combined total sample. The results indicate a substantial relevance of the verbal
      task for VWM performances in the total and the clinical sample but a low
      relevance in the healthy sample. These results could support assumptions of
      resource-depending differences in the relations of executive functioning and VWM
      but need further validation due to limitations of our study.

PMID- 25072208
TI  - Introduction to this special edition on men's mental health.

PMID- 25072206
TI  - Directly sampling the lung of a young child with cystic fibrosis reveals diverse
      microbiota.
AB  - RATIONALE: The airways of people with cystic fibrosis (CF) are chronically
      infected with a variety of bacterial species. Although routine culture methods
      are usually used to diagnose these infections, culture-independent, DNA-based
      methods have identified many bacterial species in CF respiratory secretions that
      are not routinely cultured. Many prior culture-independent studies focused either
      on microbiota in explanted CF lungs, reflecting end-stage disease, or those in
      oropharyngeal swabs, which likely sample areas in addition to the lower airways.
      Therefore, it was unknown whether the lower airways of children with CF, well
      before end-stage but with symptomatic lung disease, truly contained diverse
      microbiota. OBJECTIVES: To define the microbiota in the diseased lung tissue of a
      child who underwent lobectomy for severe, localized CF lung disease. METHODS:
      After pathologic examination verified that this child's lung tissue reflected CF
      lung disease, we used bacterial ribosomal RNA gene pyrosequencing and
      computational phylogenetic analysis to identify the microbiota in serial sections
      of the tissue. MEASUREMENTS AND MAIN RESULTS: This analysis identified diverse,
      and anatomically heterogeneous, bacterial populations in the lung tissue that
      contained both culturable and nonculturable species, including abundant
      Haemophilus, Ralstonia, and Propionibacterium species. Routine clinical cultures
      identified only Staphylococcus aureus, which represented only a small fraction of
      the microbiota found by sequencing. Microbiota analysis of an intraoperative
      oropharyngeal swab identified predominantly Streptococcus species. The
      oropharyngeal findings therefore represented the lung tissue microbiota poorly,
      in agreement with findings from earlier studies of oropharyngeal swabs in end
      stage disease. CONCLUSIONS: These results support the concept that diverse and
      spatially heterogeneous microbiota, not necessarily dominated by "traditional CF
      pathogens," are present in the airways of young, symptomatic children with early
      CF lung disease.

PMID- 25072209
TI  - Dwelling in suffering: barriers to men's healing from childhood maltreatment.
AB  - Based on findings from a hermeneutic phenomenological study, this article
      provides a description and interpretation of barriers to healing that men
      encountered in the aftermath of childhood maltreatment. An analysis of interview
      data collected from 52 adult male survivors healing from childhood maltreatment
      identified a theme, Dwelling in Suffering, as representing the full range of
      barriers that impeded their healing. Subthemes of Dwelling in Suffering
      Personally, Relationally, and Social-Environmentally are discussed. This research
      highlights a complex understanding of the challenges men experience in healing
      from childhood maltreatment and the need for practice interventions and future
      research to ameliorate men's suffering. 

PMID- 25072210
TI  - African American males diagnosed with schizophrenia: a phenomenological study.
AB  - Little is known about how African American men with schizophrenia experience
      their every day existence. Through applying interpretive phenomenology and using
      a methodological structure designed by van Manen (1990, 1997), this research
      aimed to enrich the current understanding of what it is like for these African
      American males to live with schizophrenia. In this study, five men ranging in age
      from 21 to 57 described their lives within the context of existing with the
      diagnosis of schizophrenia. The lived experiences across the interviews revealed
      four overarching themes: They know that they are mentally ill; they make a
      special effort to test reality; they assert their autonomy and; they experience
      reality differently, which they see as a gift. To provide appropriate treatment
      support to African American males diagnosed with schizophrenia, it is important
      to recognize the clients' ability to assert their autonomy and appreciate each
      man's view of himself as unique and special. Moreover, in terms of symptom
      management, it is pivotal to understand that although the client may not be free
      of hallucinations and delusions, he nevertheless may be at his optimum state of
      wellness. The realization that these men have transcended their diagnosis of
      schizophrenia rather than being crushed by their condition is evident in their
      stories. 

PMID- 25072211
TI  - Experiences of everyday life in men with alcohol dependency--a qualitative study.
AB  - The aim of the present study is to describe and understand the meaning of living
      with alcohol dependency (AD) as a man. Studies point out a high prevalence of AD
      in men and the reasons for, and consequences of, that are complex. However, today
      there is a lack of knowledge about men's lived experiences of having AD. In-depth
      interviews were conducted with 15 alcohol dependent men and analyzed using a
      phenomenological-hermeneutic approach. In the comprehensive understanding,
      findings from the naive understanding and the structural analysis were
      interpreted with help from both gender and caring theoretical perspectives. "A
      Fallible Man" and "A Man with Powerfulness" were disclosed as two main gender
      formations influencing senses of well-being. A Fallible Man involved varying
      experiences of restrictions, being in control, and meaninglessness. Being in
      control promoted a sense of well-being. A Man with Powerfulness involved
      energetic activity, and the development and maintaining of interests as well as
      risk-taking. Being powerful diminished feelings of meaninglessness, cravings, and
      social alienation. The results show, among other things, that the men live an
      incompatible life and, because of that, need support and guidance to find a more
      meaningful life. This can be accomplished if caregivers allow men to be in focus
      and involved in planning their own care. To avoid limiting the men while they are
      in treatment, the health care professionals also need to focus on the men's
      everyday life. This focus involves acknowledging the men's individual experiences
      of what enriches and limits their everyday lives. 

PMID- 25072212
TI  - Clinical characteristics and service use of incarcerated males with severe mental
      disorders: a comparative case-control study with patients found not criminally
      responsible.
AB  - Since the drop in the bed capacity of civil psychiatric hospitals, an increase in
      the bed capacity of forensic psychiatric care and prison units has been reported
      in the United States and Europe. However, in Canada, a decrease in the number of
      people with severe mental illness (SMI) during the last two decades in
      penitentiaries has been reported. At the same time, an increase in individuals
      found not criminally responsible on account of mental disorder (NCRMD) was
      observed in forensic hospitals. The aim of this study is to compare incarcerated
      severely mentally ill (I-SMI) individuals with forensic-hospitalized SMI
      individuals in terms of their clinical profiles and service use in the province
      of Quebec (Canada). A case-control study design was selected using a sample of 44
      I-SMI individuals and 59 forensic-hospitalized SMI individuals. Important
      findings include the following: I-SMI persons had less schooling; they more often
      reported suicide attempts and violent and non-violent crimes; and they had a
      higher level of comorbidity involving Cluster B personality disorders and
      substance-use disorders. Forensic-hospitalized SMI persons were more likely to
      have been receiving psychiatric follow-up before hospitalization. The final
      logistic regression model showed that lifetime suicide attempts, non-violent
      crimes, and psychopathic traits were higher among I-SMI individuals than among
      forensic-hospitalized SMI individuals. In contrast, receiving regular psychiatric
      follow-up was associated with forensic-hospitalized SMI individuals. Differences
      in psychopathological characteristics and the use of mental health services were
      found for I-SMI persons. More research is needed to determine which new
      initiatives might be efficacious in addressing the mental health needs of I-SMI
      individuals. 

PMID- 25072213
TI  - "Holes in my memories": a qualitative study of men affected by father absence.
AB  - This qualitative study explored adult men's experiences of father absence.
      Interviews with 21 men between the ages of 24 and 70 explored narratives of
      father absence and how the men perceived this influenced their life trajectory.
      Thematic analysis revealed that these men experienced a range of difficulties and
      challenges, including episodes of sadness and depression associated with loss and
      grief for the paternal relationship, self-esteem issues, feelings of anger and
      rejection, and difficulty forming trusting relationships particularly with other
      men. This study contributes to understanding mental health issues that can be
      associated with paternal absence for men. 

PMID- 25072214
TI  - Challenges and possibilities for understanding men's health in twenty-first
      century forensic psychiatric care.
AB  - Forensic psychiatric care in Sweden constitutes a specific institutional
      environment in health care in terms of gender and power relationships. This
      context emphasizes safety and protection in an environment where men constitute a
      majority of the patients and staff. It involves relationships among men's health,
      constructions of masculinities, and issues regarding equality between women's and
      men's caring work. The aim of this theoretical article is to problematize men's
      health in relation to constructions of masculinities. Our analysis shows how the
      perception of health is involved in the construction of masculinities and how
      this plays out in daily interactions between caregivers and patients. 

PMID- 25072215
TI  - Memory performance and affect: are there gender differences in community-residing
      older adults?
AB  - After age 65, the incidence of episodic memory decline in males is greater than
      in females. We explored the influence of anxiety and depression on objective and
      subjective memory performance in a diverse sample of community-residing older
      adults. The study was a secondary analysis of data on three samples of adults
      from two states, Ohio and Texas: a community sample (n = 177); a retirement
      community sample (n = 97); and the SeniorWISE Study (n = 265). The sample of 529
      adults was 74% female, the average age was 76.58 years (range = 59-100 years),
      and educational attainment was 13.12 years (+/-3.68); 68% were Caucasian, and 17%
      had depressive symptoms. We found no memory performance differences by gender.
      Males and females were similarly classified into the four memory performance
      groups, with almost half of each gender in the poor memory category. Even though
      males had greater years of education, they used fewer compensatory memory
      strategies. The observed gender differences in memory were subjective
      evaluations, specifically metamemory. Age was not a significant predictor of
      cognition or memory performance, nor did males have greater memory impairment
      than females. 

PMID- 25072217
TI  - Depression in men: issues for practice and research.

PMID- 25072216
TI  - Non-suicidal self-injury among adult males in a correctional setting.
AB  - Non-suicidal self-injury (NSSI) was thought to be a predominantly female malady
      and adult males who engage in NSSI in a correctional setting have not yet been
      well-researched. This study is, therefore, one of a few that explores the
      phenomenon of NSSI among males who engage in this behavior in a correctional
      setting. The purpose of this article is to present the demographic and
      motivational factors of adult males who engage in NSSI in a correctional setting.
      The sample consisted of 42 adult males incarcerated in three New Mexico Prisons
      who had a history of NSSI. Of the participants, 40% were Hispanic and 60% were
      non-Hispanic. Three measures were used in this study: the Deliberate Self-Harm
      Inventory (DSHI), the Self-Injury Motivational Scale-II (SIMS-II), and a
      researcher-created demographic questionnaire. The DSHI was used to examine the
      types of self-harm, as well as the frequency, severity, and duration of each
      behavior. The SIMS-II explored 36 potential types of motivations or reasons for
      self-injurious behavior. Fifteen of the 16 forms of NSSI were endorsed by at
      least one of the participants. The most predominant type of NSSI reported was
      cutting (93%), followed by head banging (78%), and sticking oneself with sharp
      objects (71.4%). Ninety-three percent of the participants required medical
      attention or hospitalization due to NSSI behaviors. Motivational factors
      associated with cutting were predominantly mood dysregulation, communication, and
      addictive qualities. 

PMID- 25072218
TI  - Quality improvement study at Mission House Clinic.
AB  - Mission House Clinic is a We-Care clinic that provides medical care to low
      income, homeless, and uninsured individuals. The Prescription Assistance Program
      (PAP) was created to bridge the gap between pharmaceutical companies that provide
      free medication and the patients at Mission House Clinic. UNF Nursing students
      have been involved with the PAP program since 2006. Previously, the PAP has
      focused on patients with respiratory diseases, hypertension, and diabetes. More
      recently, the population has shifted towards patients with mental health needs.
      The purpose of this project was to enhance the effectiveness of the PAP at
      Mission House Clinic and to improve upon the methods used to identify the
      prescription needs of the clinic population. 

PMID- 25072220
TI  - Orbital Relapsing Polychondritis: A Unique Presentation, Complication, and
      Treatment.
AB  - An 87-year-old man with a history of relapsing polychondritis presented to the
      emergency department after 4 days of worsening left periorbital swelling and
      erythema. On examination, he demonstrated clinical features consistent with
      orbital cellulitis and was treated with a trial of intravenous antibiotics. His
      condition did not improve over the next 36 hours and intravenous
      methylprednisolone was initiated. This led to rapid improvement in orbital
      symptoms and signs, and a diagnosis of specific orbital inflammation secondary to
      relapsing polychondritis was made. The patient was discharged on a tapering dose
      of prednisone. As a steroid-sparing measure, adalimumab was initiated; however,
      the patient developed Sweet Syndrome. Adalimumab was subsequently discontinued,
      steroid dose was increased, and anakinra treatment was initiated. This
      therapeutic course led to significant clinical improvement. Since initiating
      anakinra, the patient has had no recurrences of Sweet Syndrome. Anakinra may be a
      useful adjunct therapy for ophthalmic manifestations of relapsing polychondritis.

PMID- 25072221
TI  - Vision Loss After Central Retinal Artery Occlusion Secondary to Orbital Sarcoid
      Mass.
AB  - The authors describe the first report in the literature of central retinal artery
      occlusion as the presenting manifestation of sarcoidosis. A 33-year-old man with
      asthma, headache, and 6 days of intermittent, transient vision loss in the OS
      presented with persistent vision loss in the OS. Ophthalmic examination was
      consistent with diagnosis of central retinal artery occlusion in the OS. Vascular
      imaging with CT angiography revealed an incidental finding of an intraconal mass
      surrounding the left optic nerve and hilar lymphadenopathy. Broncho scopic lymph
      node biopsy demonstrated noncaseating granulomas consistent with sarcoidosis.
      This case proffers a unique mechanism of vision loss in sarcoidosis and
      highlights that atypical causes of central retinal artery occlusion must be
      considered in patients without typical risk factors.

PMID- 25072222
TI  - Primary Cutaneous Coccidioidomycosis of the Eyelid: A Case Report.
AB  - A 33-year-old man presented with an ulcerated nodule on his left eyelid and
      eyebrow that was unresponsive to broad-spectrum antibiotics. Incisional biopsies
      were performed, and cultures were positive for Coccidioides immitis. An extensive
      work-up revealed no systemic involve ment of disseminated coccidioidomycosis. The
      patient was treated with oral itraconazole for 6 months with resolution of the
      lesion. Few cases of primary cutaneous coccidioidomycosis have been reported. The
      authors describe a primary cutaneous coccidioidomycosis lesion of the eyelid
      without disseminated disease.

PMID- 25072224
TI  - Hospital-acquired pressure ulcers: magnet nurses making a difference.

PMID- 25072223
TI  - Cyclosporine-inhibitable cerebral drug transport does not influence clinical
      methadone pharmacodynamics.
AB  - BACKGROUND: Interindividual variability and drug interaction studies suggest that
      blood-brain barrier drug transporters mediate human methadone brain
      biodistribution. In vitro and animal studies suggest that methadone is a
      substrate for the efflux transporter P-glycoprotein, and that P-glycoprotein
      mediated transport influences brain access and pharmacologic effect. This
      investigation tested whether methadone is a transporter substrate in humans
      [corrected]. METHODS: Healthy volunteers received oral (N=16) or IV (N=12)
      methadone in different crossover protocols after nothing (control) or the
      validated P-glycoprotein inhibitor cyclosporine (4.5 mg/kg orally twice daily for
      4 days, or 5 mg/kg IV over 2 h). Plasma and urine methadone and metabolite
      concentrations were measured by mass spectrometry. Methadone effects were
      measured by miosis and thermal analgesia (maximally tolerated temperature and
      verbal analog scale rating of discreet temperatures). RESULTS: Cyclosporine
      marginally but significantly decreased methadone plasma concentrations and
      apparent oral clearance, but had no effect on methadone renal clearance or on
      hepatic N-demethylation. Cyclosporine had no effect on miosis or on R-methadone
      concentration-miosis relationships after either oral or IV methadone. Peak miosis
      was similar in controls and cyclosporine-treated subjects after oral methadone
      (1.4+/-0.4 and 1.3+/-0.5 mm/mg, respectively) and IV methadone (3.1+/-1.0 and
      3.2+/-0.8 mm, respectively). Methadone increased maximally tolerated temperature,
      but analgesia testing was confounded by cyclosporine-related pain. CONCLUSIONS:
      Cyclosporine did not affect methadone pharmacodynamics. This result does not
      support a role for cyclosporine-inhibitable transporters mediating methadone
      brain access and biodistribution.

PMID- 25072226
TI  - Transforming the academia-practice partnership through an innovative role design.
AB  - The director of academic nursing education was created to strengthen the
      relationship between academic nursing education and clinical practice with goals
      of advancing nurses' academic education and preparing the future pediatric
      nursing workforce for 1 organization. 

PMID- 25072225
TI  - Emergency department throughput: strategies for success.
AB  - Emergency departments are facing challenges that affect their operation such as
      overcrowding, boarding of admitted patients, poor outcomes due to extended
      waiting times to see a physician, difficulty meeting patient satisfaction
      benchmarks, and surges in patient census and acuity. Processes and procedures
      must be reviewed for effectiveness and dissected for obstacles to survive and
      flourish in the face of these challenges. In an effort to improve patient
      satisfaction, decrease waiting times, improve clinical care, and decrease lost
      revenue from patients leaving without treatment, several methods were
      investigated and implemented at the Ocean Care Center, New Jersey's 1st satellite
      emergency department. Innovations included immediate bedding, optimizing use of
      point-of-care testing, utilizing midlevel providers, utilizing protocol orders,
      and using nontraditional beds. 

PMID- 25072227
TI  - Advancing the evolution of healthcare: information technology in a person-focused
      population health model.
AB  - The current changes introduced into the healthcare delivery system through the
      Affordable Care Act require more than the isolated, quality/cost process
      solutions utilized to date. Robust information systems with capabilities to push
      information and provide valid analytics and decision support utilizing point-of
      care data input are required to achieve a complex, person-centered, lifetime
      focused model. This article presents a review of the current state of population
      health, a model identifying components within population health, and an example
      of information technology integration. 

PMID- 25072228
TI  - Care redesign: a higher-quality, lower-cost model for acute care.
AB  - OBJECTIVE: The aims of this study were to design, pilot, and evaluate a care team
      model of shared accountability on medical-surgical units. BACKGROUND: American
      healthcare systems must optimize professional nursing services and support staff
      due to economic constraints, evolving Federal regulations and increased nurse
      capabilities. METHODS: A redesigned model of RN-led teams with shared
      accountability was piloted on 3 medical/surgical units in sample hospitals for 6
      months. Nursing staff were trained for all functions within their scope of
      practice and provided education and support for implementation. RESULTS: Clinical
      outcomes and patient experience scores improved with the exception of falls.
      Nurse satisfaction demonstrated statistically significant improvement. Cost
      outcomes resulted in reduced total salary dollars per day, and case mix-adjusted
      length of stay decreased by 0.38. CONCLUSION: Innovative changes in nursing care
      delivery can maintain clinical quality and nurse and patient satisfaction while
      decreasing costs.

PMID- 25072229
TI  - An organizational intervention to influence evidence-informed decision making in
      home health nursing.
AB  - OBJECTIVE: The aims of this study were to field test and evaluate a series of
      organizational strategies to promote evidence-informed decision making (EIDM) by
      nurse managers and clinical leaders in home healthcare. BACKGROUND: EIDM is
      central to delivering high-quality and effective healthcare. Barriers exist and
      organizational strategies are needed to support EIDM. METHODS: Management and
      clinical leaders from 4 units participated in a 20-week organization-focused
      intervention. Preintervention (n = 32) and postintervention (n = 17) surveys and
      semistructured interviews (n = 15) were completed. RESULTS: Statistically
      significant increases were found on 4 of 31 survey items reflecting an increased
      organizational capacity for participants to acquire and apply research evidence
      in decision making. Support from designated facilitators with advanced skills in
      finding, appraising, and applying research was the highest rated intervention
      strategy. CONCLUSIONS: Results are useful to inform the development of
      organizational infrastructures to increase EIDM capacity in community-based
      healthcare organizations.

PMID- 25072230
TI  - The impact of opening visitation access on patient and family experience.
AB  - Restrictive visiting hours have been an obstacle to family participation in care.
      To support increased and consistent access to patients, Baylor Health Care System
      implemented a system-wide approach to open access for visitation across all
      facilities. Nursing and medical leadership led the communication efforts, and
      shared nursing governance guided revisions to existing policies. Data collected
      from 13 hospitals demonstrated that patients and families felt more informed;
      that the nursing staff were more courteous and respectful and explained things in
      a way that could be understood; that the staff attitude toward visitors was
      markedly improved; and that comfort and accommodations for guests were extended
      and improved. The resources needed to deploy these changes are outlined as well
      as the iterative process needed to create a positive impact on the family
      partnership in care. 

PMID- 25072231
TI  - Flexible working arrangements in healthcare: a comparison between managers of
      shift workers and 9-to-5 employees.
AB  - OBJECTIVE: This study examined healthcare managers' perceptions of flexible
      working arrangements and implementation barriers. BACKGROUND: Work-life conflict
      can lead to negative health implications, but flexible working arrangements can
      help manage this conflict. Little research has examined its implementation in
      24/7/365 healthcare organizations or within groups of employees working 9 AM to 5
      PM (9-5) versus shift-work hours. METHODS: Questionnaires regarding perceptions
      to, benefits of, and barriers against flexible working arrangements were
      administered to managers of 9-5 workers and shift workers in an Atlantic Canadian
      healthcare organization. RESULTS: Few differences in perceptions and benefits of
      flexible working arrangements were found between management groups. However,
      results indicate that the interaction with patients and/or the immediacy of tasks
      being performed are barriers for shift-work managers. CONCLUSIONS: The nature of
      healthcare presents barriers for managers implementing flexible working
      arrangements, which differ only based on whether the job is physical (shift work)
      versus desk related (9-5 work).

PMID- 25072232
TI  - Long-term outcomes of a postbaccalaureate nurse residency program: a pilot study.
AB  - OBJECTIVE: The purpose of this pilot study was to determine what influence a
      nurse residency program (NRP) has on long-term outcomes including turnover rates,
      career satisfaction, and leadership development. BACKGROUND: Studies examining
      short-term outcomes of NRPs have shown positive effects. Long-term studies of
      NRPs have not been reported. METHODS: This descriptive study surveyed former
      nurse residents, still employed at the facility. Data were collected by means of
      a demographic tool and the McCloskey/Mueller Satisfaction Scale, a job
      satisfaction tool. RESULTS: Although nursing turnover increased past the yearlong
      residency program, it remained well below the national average. All components of
      satisfaction were ranked relatively high, but coworker/peer support was most
      important to job satisfaction. Leadership development in the areas of
      certification and pursuing an advanced degree increased with longer employment,
      but hospital committee involvement decreased with successive cohorts. CONCLUSION:
      Overall, the long-term outcomes of an NRP appear to have benefits to both the
      organization and the individual.

PMID- 25072233
TI  - Development of a tool to measure user experience following electronic health
      record implementation.
AB  - OBJECTIVE: The aim of this study was to develop a survey tool to assess
      electronic health record (EHR) implementation to guide improvement initiatives.
      BACKGROUND: Survey tools are needed for ongoing improvement and have not been
      developed for aspects of EHR implementation. METHODS: The Baylor EHR User
      Experience (UX) survey was developed to capture 5 concept domains: training and
      competency, usability, infrastructure, usefulness, and end-user support.
      Validation efforts included content validity assessment, a pilot study, and
      analysis of 606 nurse respondents. The revised tool was sent to randomly sampled
      EHR nurse-users in 11 acute care facilities. RESULTS: A total of 1,301 nurses
      responded (37%). Internal consistency of the survey tool was excellent
      (Cronbach's alpha = .892). Survey responses including 1,819 open comments were
      used to identify and prioritize improvement efforts in areas such as education,
      support, optimization of EHR functions, and vendor change requests. CONCLUSION:
      The Baylor EHR UX survey was a valid tool that can be useful for prioritizing
      improvement efforts in relation to EHR implementation.

PMID- 25072234
TI  - Barriers to nurses' adherence to central venous catheter guidelines.
AB  - OBJECTIVE: The aim of this study was to explore nurses' perceived barriers to
      adherence of standard central venous catheter (CVC) care practices. BACKGROUND:
      Although CVC care practices are evidence based, adherence to practices may not
      always occur, contributing to nosocomial infections. Previous practice adherence
      studies focused primarily on systems improvement or observational methods. This
      pilot study explored nurses' perceptions of barriers to practice adherence.
      METHODS: A descriptive phenomenological method involving 10 participants was
      used. Data were collected through interviews and analyzed with Colaizzi's method.
      RESULTS: Data were grouped into major themes: cognitive factors (active and
      passive thinking processes) and contextual factors (patient condition along with
      materials, processes, and culture of the organization). Three connecting
      subthemes were identified. CONCLUSION: Adherence barriers have potential to
      produce errors and may limit nurses from providing high-quality care.
      Interventions to reduce barriers are needed, particularly those focused on
      resource availability and designing more intuitive processes.

PMID- 25072235
TI  - Economic analysis in medical education: definition of essential terms.
AB  - Medical education is expensive. There is a growing interest in the subject of
      cost and value in medical education. However, in the medical education
      literature, terms are sometimes used loosely - and so there is a need for basic
      grounding in the meaning of commonly used and important terms in medical
      education economics. The purpose of this article is to define some terms that are
      frequently used in economic analysis in medical education. In this article, terms
      are described, and the descriptions are followed by a worked example of how the
      terms might be used in practice. The following terms are described: opportunity
      cost, total cost of ownership, sensitivity analysis, viewpoint, activity-based
      costing, efficiency, technical efficiency, allocative efficiency, price and
      transaction costs.

PMID- 25072236
TI  - Unilateral cochlear implant use promotes normal-like loudness perception in
      adolescents with childhood deafness.
AB  - OBJECTIVES: Behavioral measures of cochlear implant (CI) device stimulation
      levels can be difficult to obtain in individuals with limited or no hearing
      experience. Loudness measures are particularly challenging. It would therefore be
      useful to have a battery of objective and behavioral measures to determine CI
      stimulation levels in listeners with childhood deafness. In the present study,
      the authors characterized loudness growth in 20 adolescents: 8 with normal
      hearing and 12 CI participants with pre/perilingual bilateral sensorineural
      hearing loss. They asked (1) do adolescent CI users with childhood deafness
      experience similar increases in loudness as their peers with normal hearing? and
      (2) can loudness be predicted by objective measures of auditory activity? The
      authors hypothesized that loudness perception would be significantly different
      between CI and normal-hearing groups and that it would correlate with objective
      measures. DESIGN: CI users were recruited from the Cochlear Implant Program at
      The Hospital for Sick Children and all had used unilateral Nucleus CIs for at
      least 2 years. The dynamic range for each participant was defined as the
      difference between the behavioral threshold and the electrically evoked stapedius
      reflex (ESR) threshold. Loudness growth was assessed within this range
      behaviorally on a continuous visual scale and objectively with physiological
      measures. Auditory brainstem responses (ABRs) and ESRs were recorded in both
      groups and electrically evoked compound action potentials (ECAPs) of the auditory
      nerve were recorded in addition in CI listeners. The regression line slopes of
      ECAP and ABR amplitude growth functions were then calculated and compared with
      behavioral loudness growth slopes in the upper portion (40-100%) and lower
      portion (0-40%) of the dynamic range. Electrical pulse stimuli (in CI users) and
      acoustic clicks (in normal-hearing participants) were presented within each
      participant's dynamic range. RESULTS: The mean dynamic range in CI listeners was
      more variable than in normal-hearing individuals. Despite this difference,
      loudness at the ESR threshold was not significantly different in CI adolescents
      from their normal-hearing peers, and CI users exhibited normal-like loudness
      growth. There was a significantly positive correlation between ECAP amplitude
      growth and loudness growth in CI users in the upper portion of the dynamic range,
      while ABR wave V amplitude growth was not related to loudness growth in either
      group. CONCLUSIONS: We confirmed that the ESR threshold is a good measure of
      comfortably loud levels in adolescents with cochlear implants and their normal
      hearing peers. Adolescents using CIs show normal-like rates of loudness growth on
      average, despite having highly variable dynamic ranges of hearing. Individual
      rates of loudness growth in the upper dynamic range in CI users can be predicted
      by the rate of amplitude growth of the ECAP. Thus, the rate of neural recruitment
      with increasing CI current is important for loudness perception in
      pre/perilingually deaf listeners and should be considered when programming their
      CIs.

PMID- 25072237
TI  - Assessing speech perception in children with cochlear implants using a modified
      hybrid visual habituation procedure.
AB  - OBJECTIVES: The objectives of this research were to determine whether an adapted
      version of a Hybrid Visual Habituation procedure could be used to assess speech
      perception of phonetic and prosodic features of speech (vowel height, lexical
      stress, and intonation) in individual pre-school-age children who use cochlear
      implants. DESIGN: Nine children ranging in age from 3;4 to 5;5 participated in
      this study. Children were prelingually deaf and used cochlear implants and had no
      other known disabilities. Children received two speech feature tests using an
      adaptation of a Hybrid Visual Habituation procedure. RESULTS: Seven of the nine
      children demonstrated perception of at least one speech feature using this
      procedure using results from a Bayesian linear regression analysis. At least one
      child demonstrated perception of each speech feature using this assessment
      procedure. CONCLUSIONS: An adapted version of the Hybrid Visual Habituation
      Procedure with an appropriate statistical analysis provides a way to assess
      phonetic and prosodicaspects of speech in pre-school-age children who use
      cochlear implants.

PMID- 25072238
TI  - Behavioral and neural discrimination of speech sounds after moderate or intense
      noise exposure in rats.
AB  - OBJECTIVES: Hearing loss is a commonly experienced disability in a variety of
      populations including veterans and the elderly and can often cause significant
      impairment in the ability to understand spoken language. In this study, we tested
      the hypothesis that neural and behavioral responses to speech will be
      differentially impaired in an animal model after two forms of hearing loss.
      DESIGN: Sixteen female Sprague-Dawley rats were exposed to one of two types of
      broadband noise which was either moderate or intense. In nine of these rats,
      auditory cortex recordings were taken 4 weeks after noise exposure (NE). The
      other seven were pretrained on a speech sound discrimination task prior to NE and
      were then tested on the same task after hearing loss. RESULTS: Following intense
      NE, rats had few neural responses to speech stimuli. These rats were able to
      detect speech sounds but were no longer able to discriminate between speech
      sounds. Following moderate NE, rats had reorganized cortical maps and altered
      neural responses to speech stimuli but were still able to accurately discriminate
      between similar speech sounds during behavioral testing. CONCLUSIONS: These
      results suggest that rats are able to adjust to the neural changes after moderate
      NE and discriminate speech sounds, but they are not able to recover behavioral
      abilities after intense NE. Animal models could help clarify the adaptive and
      pathological neural changes that contribute to speech processing in hearing
      impaired populations and could be used to test potential behavioral and
      pharmacological therapies.

PMID- 25072239
TI  - Effect of stimulus and number of sweeps on the neonate auditory brainstem
      response.
AB  - OBJECTIVES: The purpose of this study was to compare auditory brainstem responses
      (ABRs) to chirp and click stimuli in neonates at a low level typically used in
      newborn hearing screening. It was hypothesized that ABR wave V amplitudes would
      be larger and would be obtained with fewer number of stimulus presentations with
      chirps. DESIGN: Twenty-three neonates participated. ABRs were obtained to CE
      Chirp and click stimuli presented at 30 dB nHL with sweeps increasing
      exponentially in number (i.e., 116, 232, 464, 928, and 1856). RESULTS: ABRs to
      the CE-Chirps appeared before and with greater propensity at lower sweep numbers
      compared to clicks. All neonates had ABRs to CE-Chirps at 464 sweeps compared to
      1856 sweeps with the click stimulus. ABRs to CE-Chirps evidenced significantly
      larger Wave V amplitudes and significantly longer wave V latencies versus clicks.
      CONCLUSIONS: Evoking ABRs in neonates to chirps could significantly improve
      response amplitudes and reduce test time.

PMID- 25072241
TI  - Direct optical sensing of single unlabelled proteins and super-resolution imaging
      of their binding sites.
AB  - Detection of single analyte molecules without the use of any label would improve
      the sensitivity of current biosensors by orders of magnitude to the ultimate
      graininess of biological matter. Over two decades, scientists have succeeded in
      pushing the limits of optical detection to single molecules using fluorescence.
      However, restrictions in photophysics and labelling protocols make this technique
      less attractive for biosensing. Recently, mechanisms based on vibrational
      spectroscopy, photothermal detection, plasmonics and microcavities have been
      explored for fluorescence-free detection of single biomolecules. Here, we show
      that interferometric detection of scattering (iSCAT) can achieve this goal in a
      direct and label-free fashion. In particular, we demonstrate detection of cancer
      marker proteins in buffer solution and in the presence of other abundant
      proteins. Furthermore, we present super-resolution imaging of protein binding
      with nanometer localization precision. The ease of iSCAT instrumentation promises
      a breakthrough for label-free studies of interactions involving proteins and
      other small biomolecules. 

PMID- 25072240
TI  - Translating and testing the ENABLE: CHF-PC concurrent palliative care model for
      older adults with heart failure and their family caregivers.
AB  - BACKGROUND: Heart failure (HF) and palliative care (PC) organizations recommend
      early PC to improve the quality of life of patients living with HF. OBJECTIVE: We
      conducted a two-phase formative evaluation study to translate a cancer-focused
      concurrent PC intervention into one that would be appropriate for rural-dwelling
      adults with New York Heart Association Class III-IV HF and their primary
      caregivers. METHODS: Phase I: We tailored the intervention for an HF population
      via literature review, expert consultation, and clinician (N=15) small group
      interviews. Phase II: We enrolled 11 patient/caregiver dyads to assess
      intervention feasibility and satisfaction. We assessed participants' experiences
      and satisfaction after session/week three and session/week six via digitally
      recorded interviews. Clinician and participant interviews were transcribed and
      content analyzed. Outcome measures were evaluated for completion rates and effect
      sizes. RESULTS: Phase I: Clinicians described barriers to initiating PC in HF,
      triggers for initiating PC, and suggestions for intervention improvement. Phase
      II: Participants were able to complete the majority of study sessions, measures,
      and interviews. Satisfaction interviews revealed the content to be relevant and
      comprehensive in addressing HF patient and caregiver primary concerns; however,
      participants unanimously suggested making the intervention available earlier in
      the illness trajectory. Efficacy measures demonstrated small to medium effect
      sizes. CONCLUSIONS: We tailored and demonstrated feasibility of providing an
      early, concurrent palliative care intervention to patients with advanced HF and
      their caregivers. Based on this experience we are now conducting an efficacy
      trial in a racially diverse sample.

PMID- 25072242
TI  - Influence of reciprocal links in social networks.
AB  - How does reciprocal links affect the function of real social network? Does
      reciprocal link and non-reciprocal link play the same role? Previous researches
      haven't displayed a clear picture to us until now according to the best of our
      knowledge. Motivated by this, in this paper, we empirically study the influence
      of reciprocal links in two representative real datasets, Sina Weibo and Douban.
      Our results demonstrate that the reciprocal links play a more important role than
      non-reciprocal ones in information diffusion process. In particular, not only
      coverage but also the speed of the information diffusion can be significantly
      enhanced by considering the reciprocal effect. We give some possible explanations
      from the perspectives of network connectivity and efficiency. This work may shed
      some light on the in-depth understanding and application of the reciprocal effect
      in directed online social networks. 

PMID- 25072243
TI  - Urbanicity and lifestyle risk factors for cardiometabolic diseases in rural
      Uganda: a cross-sectional study.
AB  - BACKGROUND: Urban living is associated with unhealthy lifestyles that can
      increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where
      the majority of people live in rural areas, it is still unclear if there is a
      corresponding increase in unhealthy lifestyles as rural areas adopt urban
      characteristics. This study examines the distribution of urban characteristics
      across rural communities in Uganda and their associations with lifestyle risk
      factors for chronic diseases. METHODS AND FINDINGS: Using data collected in 2011,
      we examined cross-sectional associations between urbanicity and lifestyle risk
      factors in rural communities in Uganda, with 7,340 participants aged 13 y and
      above across 25 villages. Urbanicity was defined according to a multi-component
      scale, and Poisson regression models were used to examine associations between
      urbanicity and lifestyle risk factors by quartile of urbanicity. Despite all of
      the villages not having paved roads and running water, there was marked variation
      in levels of urbanicity across the villages, largely attributable to differences
      in economic activity, civil infrastructure, and availability of educational and
      healthcare services. In regression models, after adjustment for clustering and
      potential confounders including socioeconomic status, increasing urbanicity was
      associated with an increase in lifestyle risk factors such as physical inactivity
      (risk ratio [RR]: 1.19; 95% CI: 1.14, 1.24), low fruit and vegetable consumption
      (RR: 1.17; 95% CI: 1.10, 1.23), and high body mass index (RR: 1.48; 95% CI: 1.24,
      1.77). CONCLUSIONS: This study indicates that even across rural communities in
      SSA, increasing urbanicity is associated with a higher prevalence of lifestyle
      risk factors for cardiometabolic diseases. This finding highlights the need to
      consider the health impact of urbanization in rural areas across SSA. Please see
      later in the article for the Editors' Summary.

PMID- 25072245
TI  - Semi-Automatic Identification of the Fetal Profile and Nasal Bone Measurement at
      the Time of the Routine Mid-Trimester Ultrasound Scan.
AB  - PURPOSE: This study was designed to compare nasal bone length (NBL) measurements
      using a manual multiplanar mode with those made using a newer semi-automatic
      technique (Volume NTTM) acquired by an experienced operator as well as
      measurements done by two independent observers with different levels of
      ultrasound experience (conventional 2 D vs. Volume NTTM). MATERIALS AND METHODS:
      Ultrasound examination was performed prospectively on 81 pregnant women with a
      singleton pregnancy at the time of their routine mid-trimester ultrasound scan.
      RESULTS: The correct mid-sagittal plane of the fetal profile was successfully
      obtained using the semi-automatic technique in 53 of 81 cases. CONCLUSION: NBL
      measurements using conventional two-dimensional techniques showed significantly
      higher inter-observer variability than the semi-automatic program. Our study
      shows the feasibility of using a semi-automatic technique, especially for less
      experienced operators. Measurements obtained with the semi-automatic technique
      produced much less variable results around a mean than those obtained with
      conventional two-dimensional ultrasound.

PMID- 25072244
TI  - Pattern of statin use in southern italian primary care: can prescription
      databases be used for monitoring long-term adherence to the treatment?
AB  - OBJECTIVES: We sought to evaluate the prescribing pattern of statins according to
      national and regional health policy interventions and to assess specifically the
      adherence to the therapy in outpatient setting in Southern Italy. METHODS: A
      population-based study was performed on persons >=15 years old, living in the
      catchment area of Caserta (Southern Italy), and registered in Arianna database
      between 2004 and 2010. Prevalence and incidence of new treatments with statins
      were calculated for each year and stratified by drug. Adherence to therapy was
      measured by Medication Possession Ratio. Sub-analyses by individual compound and
      type of cardiovascular prevention were performed. RESULTS: From 2004 to 2010, the
      one-year prevalence of statin use increased from 44.9/1,000 inhabitants to
      79.8/1,000, respectively, consistently with the incidence of new use from
      16.2/1,000 to 19.5/1,000, except a slight decrease after criteria reimbursement
      revision on 2005 (13.3/1,000). The incidence of new treatments decreased for
      atorvastatin, and increased for simvastatin over the study years. Overall, 43% of
      new users were still highly adherent to the treatment (MPR>=80%) after six
      months, while 26% after 4-years of follow-up. As compared with highly adherent
      patients, the probability to be non-adherent (MPR<=25%) at 4-years of follow-up
      was 26% higher for women than for men (full adj. odds ratio: 1.26; 95% CI: 1.10
      1.45), and 64% higher in patients who started on primary rather than on secondary
      prevention (1.64; 1.29-2.07). CONCLUSIONS: Prevalence and incidence of statin use
      increased consistently with health policy interventions. Only one-fourth of
      patients who newly initiated a statin were adherent to the treatment after 4-year
      of follow-up. Since the benefits of statins in terms of cardiovascular outcome
      and costs are associated with their chronic use, the identification of patient
      related predictors of non-adherence such as gender, primary prevention could be
      suitable for physicians to improve the patients' compliance.

PMID- 25072246
TI  - A PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid
      induced NB4 cell differentiation.
AB  - We recently revealed that myeloid master regulator SPI1/PU.1 directly represses
      metallothionein (MT) 1G through its epigenetic activity of PU.1, but the
      functions of MT1G in myeloid differentiation remain unknown. To clarify this, we
      established MT1G-overexpressing acute promyelocytic leukemia NB4 (NB4MTOE) cells,
      and investigated whether MT1G functionally contributes to all-trans retinoic acid
      (ATRA)-induced NB4 cell differentiation. Real-time PCR analyses demonstrated that
      the inductions of CD11b and CD11c and reductions in myeloperoxidase and c-myc by
      ATRA were significantly attenuated in NB4MTOE cells. Morphological examination
      revealed that the percentages of differentiated cells induced by ATRA were
      reduced in NB4MTOE cells. Since G1 arrest is a hallmark of ATRA-induced NB4 cell
      differentiation, we observed a decrease in G1 accumulation, as well as decreases
      in p21WAF1/CIP1 and cyclin D1 inductions, by ATRA in NB4MTOE cells. Nitroblue
      tetrazolium (NBT) reduction assays revealed that the proportions of NBT-positive
      cells were decreased in NB4MTOE cells in the presence of ATRA. Microarray
      analyses showed that the changes in expression of several myeloid differentiation
      related genes (GATA2, azurocidin 1, pyrroline-5-carboxylate reductase 1, matrix
      metallopeptidase -8, S100 calcium-binding protein A12, neutrophil cytosolic
      factor 2 and oncostatin M) induced by ATRA were disturbed in NB4MTOE cells.
      Collectively, overexpression of MT1G inhibits the proper differentiation of
      myeloid cells. 

PMID- 25072247
TI  - Effects of a honeybee sting on the serum free amino acid profile in humans.
AB  - The aim of this study was to assess the response to a honeybee venom by analyzing
      serum levels of 34 free amino acids. Another goal of this study was to apply
      complex analytic-bioinformatic-clinical strategy based on up-to-date achievements
      of mass spectrometry in metabolomic profiling. The amino acid profiles were
      determined using hybrid triple quadrupole/linear ion trap mass spectrometer
      coupled with a liquid chromatography instrument. Serum samples were collected
      from 27 beekeepers within 3 hours after they were stung and after a minimum of 6
      weeks following the last sting. The differences in amino acid profiles were
      evaluated using MetaboAnalyst and ROCCET web portals. Chemometric tests showed
      statistically significant differences in the levels of L-glutamine (Gln), L
      glutamic acid (Glu), L-methionine (Met) and 3-methyl-L-histidine (3MHis) between
      the two analyzed groups of serum samples. Gln and Glu appeared to be the most
      important metabolites for distinguishing the beekeepers tested shortly after a
      bee sting from those tested at least 6 weeks later. The role of some amino acids
      in the response of an organism to the honeybee sting was also discussed. This
      study indicated that proposed methodology may allow to identify the individuals
      just after the sting and those who were stung at least 6 weeks earlier. The
      results we obtained will contribute to better understanding of the human body
      response to the honeybee sting. 

PMID- 25072248
TI  - The "gate keeper" role of Trp222 determines the enantiopreference of
      diketoreductase toward 2-chloro-1-phenylethanone.
AB  - Trp222 of diketoreductase (DKR), an enzyme responsible for reducing a variety of
      ketones to chiral alcohols, is located at the hydrophobic dimeric interface of
      the C-terminus. Single substitutions at DKR Trp222 with either canonical (Val,
      Leu, Met, Phe and Tyr) or unnatural amino acids (UAAs) (4-cyano-L-phenylalanine,
      4-methoxy-L-phenylalanine, 4-phenyl-L-phenyalanine, O-tert-butyl-L-tyrosine)
      inverts the enantiotope preference of the enzyme toward 2-chloro-1-phenylethanone
      with close side chain correlation. Analyses of enzyme activity, substrate
      affinity and ternary structure of the mutants revealed that substitution at
      Trp222 causes a notable change in the overall enzyme structure, and specifically
      in the entrance tunnel to the active center. The size of residue 222 in DKR is
      vital to its enantiotope preference. Trp222 serves as a "gate keeper" to control
      the direction of substrate entry into the active center. Consequently, opposite
      substrate-binding orientations produce respective alcohol enantiomers. 

PMID- 25072249
TI  - Molluscum contagiosum in a pediatric American Indian population: incidence and
      risk factors.
AB  - BACKGROUND: Molluscum contagiosum virus (MCV) causes an innocuous yet persistent
      skin infection in immunocompetent individuals and is spread by contact with
      lesions. Studies point to atopic dermatitis (AD) as a risk factor for MCV
      infection; however, there are no longitudinal studies that have evaluated this
      hypothesis. METHODS: Outpatient visit data from fiscal years 2001-2009 for
      American Indian and Alaska Native (AI/AN) children were examined to describe the
      incidence of molluscum contagiosum (MC). We conducted a case-control study of
      patients <5 years old at an Indian Health Service (IHS) clinic to evaluate
      dermatological risk factors for infection. RESULTS: The incidence rate for MC in
      children <5 years old was highest in the West and East regions. MC cases were
      more likely to have a prior or co-occurring diagnosis of eczema, eczema or
      dermatitis, impetigo, and scabies (p<0.05) compared to controls; 51.4% of MC
      cases had a prior or co-occurring diagnosis of eczema or dermatitis. CONCLUSIONS:
      The present study is the first demonstration of an association between AD and MC
      using a case-control study design. It is unknown if the concurrent high incidence
      of eczema and MC is related, and this association deserves further investigation.

PMID- 25072250
TI  - Do we notice when communication goes awry? An investigation of people's
      sensitivity to coherence in spontaneous conversation.
AB  - In the dominant theoretical framework, human communication is modeled as the
      faithful transmission of information. This implies that when people are involved
      in communicational exchanges, they should be sensitive to the success with which
      information is transmitted, easily detecting when conversations lack coherence.
      The expectation that humans are good at detecting conversational incoherence is
      in line with common intuition, but there are several reasons to suspect that it
      might be unrealistic. First, similar intuitions have been shown to be unrealistic
      for a number of psychological processes. Second, faithful information
      transmission may conflict with other conversational goals. Third, mechanisms
      supporting information transmission may themselves lead to cases of incoherence
      being missed. To ascertain the extent to which people are insensitive to patches
      of serious conversational incoherence, we generated such patches in the
      laboratory by repeatedly crossing two unrelated conversations. Across two
      studies, involving both narrowly and broadly focused conversations, between 27%
      and 42% of the conversants did not notice that their conversations had been
      crossed. The results of these studies suggest that it may indeed be unrealistic
      to model spontaneous conversation as faithful information transmission. Rather,
      our results are more consistent with models of communication that view it as
      involving noisy and error-prone inferential processes, serving multiple
      independent goals. 

PMID- 25072252
TI  - Development of an acellular tumor extracellular matrix as a three-dimensional
      scaffold for tumor engineering.
AB  - Tumor engineering is defined as the construction of three-dimensional (3D) tumors
      in vitro with tissue engineering approaches. The present 3D scaffolds for tumor
      engineering have several limitations in terms of structure and function. To get
      an ideal 3D scaffold for tumor culture, A549 human pulmonary adenocarcinoma cells
      were implanted into immunodeficient mice to establish xenotransplatation models.
      Tumors were retrieved at 30-day implantation and sliced into sheets. They were
      subsequently decellularized by four procedures. Two decellularization methods,
      Tris-Trypsin-Triton multi-step treatment and sodium dodecyl sulfate (SDS)
      treatment, achieved complete cellular removal and thus were chosen for evaluation
      of histological and biochemical properties. Native tumor tissues were used as
      controls. Human breast cancer MCF-7 cells were cultured onto the two 3D scaffolds
      for further cell growth and growth factor secretion investigations, with the two
      dimensional (2D) culture and cells cultured onto the Matrigel scaffolds used as
      controls. Results showed that Tris-Trypsin-Triton multi-step treated tumor sheets
      had well-preserved extracellular matrix structures and components. Their porosity
      was increased but elastic modulus was decreased compared with the native tumor
      samples. They supported MCF-7 cell repopulation and proliferation, as well as
      expression of growth factors. When cultured within the Tris-Trypsin-Triton
      treated scaffold, A549 cells and human colorectal adenocarcinoma cells (SW-480)
      had similar behaviors to MCF-7 cells, but human esophageal squamous cell
      carcinoma cells (KYSE-510) had a relatively slow cell repopulation rate. This
      study provides evidence that Tris-Trypsin-Triton treated acellular tumor
      extracellular matrices are promising 3D scaffolds with ideal spatial arrangement,
      biomechanical properties and biocompatibility for improved modeling of 3D tumor
      microenvironments. 

PMID- 25072254
TI  - Health professionals as mobile content creators: teaching medical students to
      develop mHealth applications.
AB  - INTRODUCTION: Patient access to health information and patient-provider
      communication is integral to medicine, and can be facilitated by mobile
      applications ("apps"). Traditionally, student training in mobile Health (mHealth)
      has focussed on health professionals as consumers of information, with negative
      impacts on the quality and value of medical apps. This study focuses on teaching
      medical students to develop their own medical apps. METHODS: At Sultan Qaboos
      University, Oman, an app development environment, iBuildApp, was taught to
      medical students and used to develop their first apps. Students were surveyed on
      their perceptions of the project. RESULTS: Of the 166 students, 107 (64.5%)
      completed the survey. There was an increase in the perceived need for such
      learning, apps were aimed primarily at patients, and previous programming
      experience was the strongest influencer of a positive experience. A majority
      (77.6%) wanted more sophisticated development environments in spite of their
      apparent struggles. DISCUSSIONS: The impact of previous experience is similar to
      other studies; the perceived value and focus on patient apps is indicative of an
      awareness of patients' use of the devices not reflected in all literature.
      CONCLUSION: It is possible to teach medical students the fundamentals of app
      design so that they may contribute to app development in the future.

PMID- 25072253
TI  - Identification of polyketide inhibitors targeting 3-dehydroquinate dehydratase in
      the shikimate pathway of Enterococcus faecalis.
AB  - Due to the emergence of resistance toward current antibiotics, there is a
      pressing need to develop the next generation of antibiotics as therapeutics
      against infectious and opportunistic diseases of microbial origins. The shikimate
      pathway is exclusive to microbes, plants and fungi, and hence is an attractive
      and logical target for development of antimicrobial therapeutics. The Gram
      positive commensal microbe, Enterococcus faecalis, is a major human pathogen
      associated with nosocomial infections and resistance to vancomycin, the "drug of
      last resort". Here, we report the identification of several polyketide-based
      inhibitors against the E. faecalis shikimate pathway enzyme, 3-dehydroquinate
      dehydratase (DHQase). In particular, marein, a flavonoid polyketide, both
      inhibited DHQase and retarded the growth of Enterococcus faecalis. The
      purification, crystallization and structural resolution of recombinant DHQase
      from E. faecalis (at 2.2 A resolution) are also reported. This study provides a
      route in the development of polyketide-based antimicrobial inhibitors targeting
      the shikimate pathway of the human pathogen E. faecalis. 

PMID- 25072255
TI  - A multicentre retrospective comparison of central nervous system prophylaxis
      strategies among patients with high-risk diffuse large B-cell lymphoma.
AB  - BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma
      (DLBCL) is a devastating complication; the optimal prophylactic strategy remains
      unclear. METHODS: We performed a multicentre, retrospective analysis of patients
      with DLBCL with high risk for CNS relapse as defined by two or more of: multiple
      extranodal sites, elevated serum LDH and B symptoms or involvement of specific
      high-risk anatomical sites. We compared three different strategies of CNS
      directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R
      CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose
      intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or
      CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were
      identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of
      3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3
      respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5
      33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively
      (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was
      associated with lower incidence of CNS relapse compared with IT chemotherapy
      alone. However, these data are limited by their retrospective nature and warrant
      confirmation in prospective randomised studies.

PMID- 25072256
TI  - Comparing primary and secondary health-care use between diagnostic routes before
      a colorectal cancer diagnosis: cohort study using linked data.
AB  - BACKGROUND: Survival in cancer patients diagnosed following emergency
      presentations is poorer than those diagnosed through other routes. To identify
      points for intervention to improve survival, a better understanding of patients'
      primary and secondary health-care use before diagnosis is needed. Our aim was to
      compare colorectal cancer patients' health-care use by diagnostic route. METHODS:
      Cohort study of colorectal cancers using linked primary and secondary care and
      cancer registry data (2009-2011) from four London boroughs. The prevalence of all
      and relevant GP consultations and rates of primary and secondary care use up to
      21 months before diagnosis were compared across diagnostic routes (emergency, GP
      referred and consultant/other). RESULTS: The data set comprised 943 colorectal
      cancers with 24% diagnosed through emergency routes. Most (84%) emergency
      patients saw their GP 6 months before diagnosis but their symptom profile was
      distinct; fewer had symptoms meeting urgent referral criteria than GP-referred
      patients. Compared with GP-referred, emergency patients used primary care less
      (IRR: 0.85 (95% CI 0.78-0.93)) and urgent care more frequently (IRR: 1.56 (95% CI
      1.12; 2.17)). CONCLUSIONS: Distinct patterns of health-care use in patients
      diagnosed through emergency routes were identified in this cohort. Such analyses
      using linked data can inform strategies for improving early diagnosis of
      colorectal cancer.

PMID- 25072257
TI  - The prognostic value and therapeutic target role of stathmin-1 in urinary bladder
      cancer.
AB  - BACKGROUND: The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression
      and migration, is associated with clinical outcome in breast cancer. Here we aim
      to investigate its clinical significance in urinary bladder cancer and its
      possibilities as a therapeutic target. METHODS: Immunohistochemical analyses of
      STMN1 protein expression were performed in three patient cohorts: cohort I (n=115
      Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled
      trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90
      T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated
      in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular
      expression using siRNA. RESULTS: In cohort I, high STMN1 expression correlated to
      shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval
      (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels
      (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04
      2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients
      were STMN1-positive in both the primary tumour and matched metastases. In vitro,
      the growth and migration of the T24 cells were significantly reduced (P<0.01,
      P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.
      CONCLUSIONS: STMN1 protein expression has prognostic significance but is
      primarily a potential treatment target in urinary bladder cancer.

PMID- 25072258
TI  - The role of biological therapy in metastatic colorectal cancer after first-line
      treatment: a meta-analysis of randomised trials.
AB  - PURPOSE: Biologic agents have achieved variable results in relapsed metastatic
      colorectal cancer (mCRC). Systematic meta-analysis was undertaken to determine
      the efficacy of biological therapy. METHODS: Major databases were searched for
      randomised studies of mCRC after first-line treatment comparing (1) standard
      treatment plus biologic agent with standard treatment or (2) standard treatment
      with biologic agent with the same treatment with different biologic agent(s).
      Data were extracted on study design, participants, interventions and outcomes.
      Study quality was assessed using the MERGE criteria. Comparable data were pooled
      for meta-analysis. RESULTS: Twenty eligible studies with 8225 patients were
      identified. The use of any biologic therapy improved overall survival with hazard
      ratio (HR) 0.87 (95% confidence interval (CI) 0.82-0.91, P<0.00001), progression
      free survival (PFS) with HR 0.71 (95% CI 0.67-0.74, P<0.0001) and overall
      response rate (ORR) with odds ratio (OR) 2.38 (95% CI 2.03-2.78, P<0.00001).
      Grade 3/4 toxicity was increased with OR 2.34. Considering by subgroups, EGFR
      inhibitors (EGFR-I) in the second-line setting and anti-angiogenic therapies
      (both in second-line and third-line and beyond settings) all improved overall
      survival, PFS and ORR. EGFR-I in third-line settings improved PFS and ORR but not
      OS. CONCLUSIONS: The use of biologic agents in mCRC after first-line treatment is
      associated with improved outcomes but increased toxicity.

PMID- 25072259
TI  - Glutamine depletion by crisantaspase hinders the growth of human hepatocellular
      carcinoma xenografts.
AB  - BACKGROUND: A subset of human hepatocellular carcinomas (HCC) exhibit mutations
      of beta-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1
      mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro
      with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L
      sulfoximine (MSO). METHODS: Immunodeficient mice with subcutaneous xenografts of
      the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with
      Crisantaspase and/or MSO, and tumour growth was monitored. At the end of
      treatment, tumour weight and histology were assessed. Serum and tissue amino
      acids were determined by HPLC. Gene and protein expression were estimated with RT
      PCR and western blot and GS activity with a colorimetric method. mTOR activity
      was evaluated from the phosphorylation of p70S6K1. RESULTS: Crisantaspase and MSO
      depleted serum glutamine, lowered glutamine in liver and tumour tissue, and
      inhibited liver GS activity. HepG2 tumour growth was significantly reduced by
      either Crisantaspase or MSO, and completely suppressed by the combined treatment.
      The combined treatment was also effective against xenografts of the HC-AFW1 cell
      line, which is Crisantaspase resistant in vitro. CONCLUSIONS: The combination of
      Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts
      and hinders their growth.

PMID- 25072263
TI  - Osteoarthritis: From arthritis to omega--PUFAs regulate OA in obesity.

PMID- 25072260
TI  - Prostate cancer cell malignancy via modulation of HIF-1alpha pathway with
      isoflurane and propofol alone and in combination.
AB  - BACKGROUND: Surgery is considered to be the first line treatment for solid
      tumours. Recently, retrospective studies reported that general anaesthesia was
      associated with worse long-term cancer-free survival when compared with regional
      anaesthesia. This has important clinical implications; however, the mechanisms
      underlying those observations remain unclear. We aim to investigate the effect of
      anaesthetics isoflurane and propofol on prostate cancer malignancy. METHODS:
      Prostate cancer (PC3) cell line was exposed to commonly used anaesthetic
      isoflurane and propofol. Malignant potential was assessed through evaluation of
      expression level of hypoxia-inducible factor-1alpha (HIF-1alpha) and its
      downstream effectors, cell proliferation and migration as well as development of
      chemoresistance. RESULTS: We demonstrated that isoflurane, at a clinically
      relevant concentration induced upregulation of HIF-1alpha and its downstream
      effectors in PC3 cell line. Consequently, cancer cell characteristics associated
      with malignancy were enhanced, with an increase of proliferation and migration,
      as well as development of chemoresistance. Inhibition of HIF-1alpha neosynthesis
      through upper pathway blocking by a PI-3K-Akt inhibitor or HIF-1alpha siRNA
      abolished isoflurane-induced effects. In contrast, the intravenous anaesthetic
      propofol inhibited HIF-1alpha activation induced by hypoxia or CoCl2. Propofol
      also prevented isoflurane-induced HIF-1alpha activation, and partially reduced
      cancer cell malignant activities. CONCLUSIONS: Our findings suggest that
      modulation of HIF-1alpha activity by anaesthetics may affect cancer recurrence
      following surgery. If our data were to be extrapolated to the clinical setting,
      isoflurane but not propofol should be avoided for use in cancer surgery. Further
      work involving in vivo models and clinical trials is urgently needed to determine
      the optimal anaesthetic regimen for cancer patients.

PMID- 25072261
TI  - Overall survival and clinical characteristics of pancreatic cancer in BRCA
      mutation carriers.
AB  - BACKGROUND: The BRCA1/2 proteins are involved in regulation of cellular
      proliferation by DNA damage repair via homologous recombination. Therefore,
      BRCA1/2 mutation carriers with pancreatic cancer may have distinct biologic
      outcomes. METHODS: Patients with BRCA1/2-associated pancreatic ductal
      adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were
      identified from databases at three participating institutions. Clinical data were
      collected. Disease-free survival and overall survival (OS) were analysed.
      RESULTS: Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both
      (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33
      83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent
      primary resection. Out of 71 participants, 12 received experimental therapy; one
      patient had missing data, these 13 cases were excluded from OS analysis. Median
      OS for 58 patients was 14 months (95% CI 10-23 months). Median OS for patients
      with stage 1/2 disease has not been reached with 52% still alive at 60 months.
      Median OS for stage 3/4 was 12 months (95% CI 6-15). Superior OS was observed for
      patients with stage 3/4 treated with platinum vs those treated with non-platinum
      chemotherapies (22 vs 9 months; P=0.039). CONCLUSION: Superior OS was observed
      for advanced-disease BRCA-associated PDAC with platinum exposure.

PMID- 25072265
TI  - Experimental arthritis: Fire and ice: syndecan-3 in inflammation.

PMID- 25072264
TI  - Lungs, joints and immunity against citrullinated proteins in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a prototype for a criterion-defined inflammatory
      disease, for which the aetiology and initial molecular pathogenesis has been
      elusive for a long time. We describe in this Review how studies on the interplay
      between specific immunity, alongside genetic and environmental predisposing
      factors, provide new tools to understand the molecular basis of distinct subsets
      of the disease. A particular emphasis is on the possibility that pathogenic
      immune reactions might be initiated at other sites than the joints, and that the
      lungs could harbour such sites. New data strengthen this concept, showing that
      local immunity towards citrullinated proteins and accompanying inflammation might
      be present in the lungs early during disease development. This progress makes RA
      an interesting case for the future development of therapies that might be
      directed against disease-inducing immunity even before inflammation and
      destruction of joints has begun.

PMID- 25072266
TI  - Challenges of climate change: omics-based biology of saffron plants and organic
      agricultural biotechnology for sustainable saffron production.
AB  - Kashmir Valley is a major saffron (Crocus sativus Kashmirianus) growing area of
      the world, second only to Iran in terms of production. In Kashmir, saffron is
      grown on uplands (termed in the local language as "Karewas"), which are
      lacustrine deposits located at an altitude of 1585 to 1677 m above mean sea level
      (amsl), under temperate climatic conditions. Kashmir, despite being one of the
      oldest historical saffron-producing areas, faces a rapid decline of saffron
      industry. Among many other factors responsible for decline of saffron industry
      the preponderance of erratic rainfalls and drought-like situation have become
      major challenges imposed by climate change. Saffron has a limited coverage area
      as it is grown as a 'niche crop' and is a recognized "geographical indication,"
      growing under a narrow microclimatic condition. As such it has become a victim of
      climate change effects, which has the potential of jeopardizing the livelihood of
      thousands of farmers and traders associated with it. The paper discusses the
      potential and actual impact of climate change process on saffron cultivation in
      Kashmir; and the biotechnological measures to address these issues.

PMID- 25072267
TI  - Stereoselective acylation of the E,E-vinylketene silyl N,O-acetal and its
      application to the synthesis of khafrefungin.
AB  - Stereoselective acylation of the E,E-vinylketene silyl N,O-acetal possessing a
      chiral auxiliary has been achieved by using acid anhydrides and SnCl4. Acid
      anhydrides having alkyl chains gave the adducts in excellent stereoselectivity.
      The formal synthesis of khafrefungin has been accomplished by the methodology. 

PMID- 25072268
TI  - Fingerprinting of hydroxyl radical-attacked polysaccharides by N-isopropyl-2
      aminoacridone labelling.
AB  - Hydroxyl radicals (*OH) cause non-enzymic scission of polysaccharides in diverse
      biological systems. Such reactions can be detrimental (e.g. causing rheumatic and
      arthritic diseases in mammals) or beneficial (e.g. promoting the softening of
      ripening fruit, and biomass saccharification). Here we present a method for
      documenting *OH action, based on fluorescent labelling of the oxo groups that are
      introduced as glycosulose residues when *OH attacks polysaccharides. The method
      was tested on several polysaccharides, especially pectin, after treatment with
      Fenton reagents. 2-Aminoacridone plus cyanoborohydride reductively aminated the
      oxo groups in treated polysaccharides; the product was then reacted with acetone
      plus cyanoborohydride, forming a stable tertiary amine with the carbohydrate
      linked to N-isopropyl-2-aminoacridone (pAMAC). Digestion of labelled pectin with
      'Driselase' yielded several fluorescent products which on electrophoresis and
      HPLC provided a useful 'fingerprint' indicating *OH attack. The most diagnostic
      product was a disaccharide conjugate of the type pAMAC.UA-GalA (UA=unspecified
      uronic acid), whose UA-GalA bond was Driselase-resistant (product 2A). 2A was
      clearly distinguishable from GalA-GalA-pAMAC (disaccharide labelled at its
      reducing end), which was digestible to GalA-pAMAC. The methodology is applicable,
      with appropriate enzymes in place of Driselase, for detecting natural and
      artificial *OH attack in diverse plant, animal and microbial polysaccharides. 

PMID- 25072271
TI  - Closed-loop system in the management of diabetes: past, present, and future.
AB  - Intensive insulin therapy (IIT) has been shown to reduce micro- and macrovascular
      complications in patients with type 1 diabetes mellitus (T1DM). However, IIT is
      associated with a significant increase in severe hypoglycemic events, resulting
      in increased morbidity and mortality. Optimization of glycemic control without
      hypoglycemia (especially nocturnal) should be the next major goal for subjects on
      insulin treatment. The use of insulin pumps along with continuous glucose
      monitors (CGMs) has made it easier but requires significant resources and patient
      education. Research is ongoing to close the loop by integrating the pump and the
      CGM using different algorithms. The currently available closed-loop system is the
      threshold suspend. Steps needed to achieve a near-perfect closed-loop are (1) a
      control-to-range system that will reduce the incidence and/or severity of hyper-
      and/or hypoglycemia by adjusting the insulin dose and (2) a control-to-target
      system, a fully automated or hybrid system that sets target glucose levels to
      individual needs and maintains glucose levels throughout the day using insulin
      (unihormonal) alone or with other hormones such as glucagon or possibly
      pramlintide (bihormonal). Future research is also focusing on better insulin
      delivery devices (pumps), more accurate CGMs, better predictive algorithms, and
      ultra-rapid-acting insulin analogs to make the closed-loop system as
      physiological as possible.

PMID- 25072269
TI  - Association between intake of sugar-sweetened beverages and circulating 25
      hydroxyvitamin D concentration among premenopausal women.
AB  - Intake of sugar-sweetened beverages has increased in North America and seems to
      have several adverse health effects possibly through decreased circulating 25
      hydroxyvitamin D (25(OH)D) concentrations. The aim of this cross-sectional study
      was to evaluate the association between sugar-sweetened beverages intake and
      25(OH)D concentrations among premenopausal women. Intake of sugar-sweetened
      beverages including colas, other carbonated beverages and sweet fruit drinks was
      assessed using a validated food frequency questionnaire among 741 premenopausal
      women. Plasma concentrations of 25(OH)D were quantified by radioimmunoassay. The
      association between sugar-sweetened beverages intake and 25(OH)D concentrations
      was evaluated using multivariate generalized linear models and Spearman
      correlations. A higher intake of colas was associated with lower mean 25(OH)D
      levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1-3 and >3 servings/week,
      respectively; r = -0.11 (p = 0.004)). A correlation was observed between intake
      of other carbonated beverages and 25(OH)D concentrations but was not
      statistically significant (r = -0.06 (p = 0.10)). No association was observed
      between intake of sweet fruit drinks and 25(OH)D concentrations. This study
      suggests that high intake of colas may decrease 25(OH)D levels in premenopausal
      women. Considering the high consumption of these drinks in the general population
      and the possible consequences of vitamin D deficiency on health, this finding
      needs further investigation. 

PMID- 25072272
TI  - Brain-specific delivery of dopamine mediated by n,n-dimethyl amino group for the
      treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) has become one of the most deadly diseases due to a lack
      of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3
      (dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was
      designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl
      amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was
      investigated both in vitro and in vivo by comparing with L-DOPA and another
      derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced
      accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via
      an active transport process. The increased cellular uptake of PDDP was proven to
      be mediated by putative pyrilamine cationic transporters. Following intravenous
      administration, the concentration of PDDP in the brain was 269.28-fold and 6.41
      fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally,
      PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6
      OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic
      effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus,
      N,N-dimethyl amino group-based PDDP represents an effective and safe treatment
      for PD. 

PMID- 25072273
TI  - Density functional theory study on the full ALD process of silicon nitride thin
      film deposition via BDEAS or BTBAS and NH3.
AB  - A detailed reaction mechanism has been proposed for the full ALD cycle of Si3N4
      deposition on the beta-Si3N4(0001) surface using bis(diethylamino)silane (BDEAS)
      or bis(tertiarybutylamino)silane (BTBAS) as a Si precursor with NH3 acting as the
      nitrogen source. Potential energy landscapes were derived for all elementary
      steps in the proposed reaction network using a periodic slab surface model in the
      density functional approximation. Although the dissociative reactivity of BTBAS
      was slightly better than that of BDEAS, the thermal deposition process was still
      found to be an inherently high temperature process due to the high activation
      energies during the dissociative chemisorption of both precursors and the surface
      re-amination steps. These results underline the need to develop new precursors
      and alternative nitrogen sources when low temperature thermal silicon nitride
      films are targeted. 

PMID- 25072274
TI  - High intensity focused ultrasound responsive metallo-supramolecular block
      copolymer micelles.
AB  - The metal-supramolecular diblock copolymer containing mechano-labile
      bis(terpyridine)-Cu(II) complex linkage in the junction point was synthesized.
      These metal-ligand containing amphiphilic copolymers are able to self-assemble in
      aqueous solution to form spherical micelles with poly(propylene glycol) block
      forming the hydrophobic core. It is found that high intensity focused ultrasound
      can open the copolymer micelles and trigger the release of the payload in the
      micelle. The micellar properties and release kinetics of encapsulated guest
      molecule in response to ultrasound stimuli were investigated. The weak Cu(II)
      terpyridine dynamic bond in the copolymer chain can be cleaved under ultrasound
      and thus leads to the disruption of the copolymer micelle and the release of
      loaded cargo. This study will open up a new way for the molecular design of
      ultrasound modulated drug delivery systems. 

PMID- 25072275
TI  - Oh, no--equations! Reanalysis of the data reveal even stronger associations
      between Hashimoto's thyroiditis and differentiated thyroid cancer.

PMID- 25072276
TI  - Magnetic particle-scanning for ultrasensitive immunodetection on-chip.
AB  - We describe the concept of magnetic particle-scanning for on-chip detection of
      biomolecules: a magnetic particle, carrying a low number of antigens (Ag's) (down
      to a single molecule), is transported by hydrodynamic forces and is subjected to
      successive stochastic reorientations in an engineered magnetic energy landscape.
      The latter consists of a pattern of substrate-bound small magnetic particles that
      are functionalized with antibodies (Ab's). Subsequationuent counting of the
      captured Ag-carrying particles provides the detection signal. The magnetic
      particle-scanning principle is investigated in a custom-built magneto
      microfluidic chip and theoretically described by a random walk-based model, in
      which the trajectory of the contact point between an Ag-carrying particle and the
      small magnetic particle pattern is described by stochastic moves over the surface
      of the mobile particle, until this point coincides with the position of an Ag,
      resulting in the binding of the particle. This model explains the particular
      behavior of previously reported experimental dose-response curves obtained for
      two different ligand-receptor systems (biotin/streptavidin and TNF-alpha) over a
      wide range of concentrations. Our model shows that magnetic particle-scanning
      results in a very high probability of immunocomplex formation for very low Ag
      concentrations, leading to an extremely low limit of detection, down to the
      single molecule-per-particle level. When compared to other types of magnetic
      particle-based surface coverage assays, our strategy was found to offer a wider
      dynamic range (>8 orders of magnitude), as the system does not saturate for
      concentrations as high as 10(11) Ag molecules in a 5 MUL drop. Furthermore, by
      emphasizing the importance of maximizing the encounter probability between the Ag
      and the Ab to improve sensitivity, our model also contributes to explaining the
      behavior of other particle-based heterogeneous immunoassays. 

PMID- 25072278
TI  - Large-scale and environmentally friendly synthesis of pH-responsive oil-repellent
      polymer brush surfaces under ambient conditions.
AB  - Contrary to conventional ATRP, aqueous A(R)GET-ATRP at ambient temperature
      without deoxygenating reaction solutions is an extremely facile method to create
      polymer brushes. Using these techniques, extremely thick poly[2
      (dimethylamino)ethyl methacrylate] polymer brushes can be prepared (~700 nm), or
      reaction solutions can be low chemical-content, consisting of 99% v/v water.
      Based on these techniques, we have also developed an easy and inexpensive method,
      referred to as "paint on"-ATRP, that directly pastes reaction solutions onto
      various large-scale real-life substrates open to the air. The resulting brush
      surfaces possess excellent oil-repellent properties, which can be activated or
      deactivated in response to solution pH. 

PMID- 25072277
TI  - Short term morphine exposure in vitro alters proliferation and differentiation of
      neural progenitor cells and promotes apoptosis via mu receptors.
AB  - BACKGROUND: Chronic morphine treatment inhibits neural progenitor cell (NPC)
      progression and negatively effects hippocampal neurogenesis. However, the effect
      of acute opioid treatment on cell development and its influence on NPC
      differentiation and proliferation in vitro is unknown. We aim to investigate the
      effect of a single, short term exposure of morphine on the proliferation,
      differentiation and apoptosis of NPCs and the mechanism involved. METHODS: Cell
      cultures from 14-day mouse embryos were exposed to different concentrations of
      morphine and its antagonist naloxone for 24 hours and proliferation,
      differentiation and apoptosis were studied. Proliferating cells were labeled with
      bromodeoxyuridine (BrdU) and cell fate was studied with immunocytochemistry.
      RESULTS: Cells treated with morphine demonstrated decreased BrdU expression with
      increased morphine concentrations. Analysis of double-labeled cells showed a
      decrease in cells co-stained for BrdU with nestin and an increase in cells co
      stained with BrdU and neuron-specific class III beta-tubuline (TUJ1) in a dose
      dependent manner. Furthermore, a significant increase in caspase-3 activity was
      observed in the nestin- positive cells. Addition of naloxone to morphine-treated
      NPCs reversed the anti-proliferative and pro-apoptotic effects of morphine.
      CONCLUSIONS: Short term morphine exposure induced inhibition of NPC proliferation
      and increased active caspase-3 expression in a dose dependent manner. Morphine
      induces neuronal and glial differentiation and decreases the expression of nestin
      positive cells. These effects were reversed with the addition of the opioid
      antagonist naloxone. Our results demonstrate the effects of short term morphine
      administration on the proliferation and differentiation of NPCs and imply a mu
      receptor mechanism in the regulation of NPC survival.

PMID- 25072279
TI  - Prefrontal cortex reactivity underlies trait vulnerability to chronic social
      defeat stress.
AB  - Psychological stress contributes to the onset and exacerbation of nearly all
      neuropsychiatric disorders. Individual differences in stress-regulatory circuits
      can therefore dramatically affect vulnerability to these illnesses. Here we
      identify neural circuit mechanisms underlying individual differences in
      vulnerability to stress using a murine model of chronic social defeat stress. In
      chronically stressed mice, we find that the degree of prefrontal cortex (PFC)
      control of amygdala activity predicts stress susceptibility in individual mice.
      Critically, we also find that individual differences in PFC activation (that is,
      reactivity) during exposure to an aggressor mouse predict the emergence stress
      induced behavioural deficits in stress-naive mice. Finally, we show that
      naturally occurring differences in PFC reactivity directly correspond to the
      intrinsic firing rate of PFC neurons. This demonstrates that naturally occurring
      differences in PFC function underlie individual differences in vulnerability to
      stress, raising the hypothesis that PFC modulation may prevent stress-induced
      psychiatric disorders. 

PMID- 25072280
TI  - The synergistic effect of organic silicone quaternary ammonium salt and 5
      fluorouracil on hepatocellular carcinoma in vitro and in vivo.
AB  - Hepatocellular carcinoma (HCC) is the third most common type of cancer worldwide,
      causing over 370,000 deaths per year, with approximately half of them in China.
      Chemotherapy is the optimal treatment for patients with advanced HCC, although
      chemoresistance has become a significant obstacle to successful liver cancer
      surgery. In this paper, we have assessed the characteristics of drugs to explore
      the effects of individual and combined action of organic silicone quaternary
      ammonium salt (Jieyoushen) and 5-fluorouracil (5-FU). The results of MTT assays
      showed that single and combined action of Jieyoushen and 5-FU can inhibit the
      proliferation of liver carcinoma cell lines in a dose-dependent and time
      dependent manner, respectively. Electron microscopy and Hoechst 33342 staining
      showed characteristic apoptotic bodies in apoptotic cells treated with Jieyoushen
      and 5-FU. Flow cytometry results indicated that the percentage of cells at G0/G1
      phase gradually increased, whereas it gradually decreased during the S phase
      after treatment. Taken together, these results suggest that the combination of
      Jieyoushen with 5-FU exerts a synergistic anticancer effect on HCC growth and
      that targeted therapeutic strategies may improve HCC sensitivity to chemotherapy.

PMID- 25072281
TI  - Prophylactic cranial irradiation may impose a detrimental effect on overall
      survival of patients with nonsmall cell lung cancer: a systematic review and meta
      analysis.
AB  - PURPOSE: To determine the role of brain metastases (BM) and overall survival (OS)
      in patients with non-small cell lung cancer (NSCLC) by performing a meta-analysis
      of the RCTs (randomized controlled clinical trials) and non-RCTs (non-randomized
      controlled clinical trials) published in the literature. METHODS: A meta-analysis
      was performed using trials identified through PubMed, EMBASE and Cochrane
      databases. Two investigators independently assessed the quality of the trials and
      extracted data. The outcomes included BM, OS, median survival (MS), response rate
      (RR), Hazard ratios (HRs) and odds ratios (ORs), and their 95% confidence
      intervals (CIs) were pooled using ReMan software. RESULTS: Twelve trials (6 RCTs
      and 6 non-RCTs) involving 1,718 NSCLC patients met the inclusion criteria. They
      were grouped on the basis of study design for separate Meta-analyses. The results
      showed that prophylactic cranial irradiation (PCI) reduced the risk of BM as
      compared with non-PCI in NSCLC patients (OR = 0.30, 95% [CI]: 0.21-0.43,
      p<0.00001). However, HRs for OS favored non-PCI (HR = 1.19, 95% [CI]: 1.06-1.33,
      p = 0.004), without evidence of heterogeneity between the studies. CONCLUSION:
      Our results suggest that although PCI decreased the risk of BM, it may impose a
      detrimental effect on OS of NSCLC patients.

PMID- 25072282
TI  - Differential expression of heat shock transcription factors and heat shock
      proteins after acute and chronic heat stress in laying chickens (Gallus gallus).
AB  - Heat stress due to high environmental temperature negatively influences animal
      performances. To better understand the biological impact of heat stress, laying
      broiler breeder chickens were subjected either to acute (step-wisely increasing
      temperature from 21 to 35 degrees C within 24 hours) or chronic (32 degrees C for
      8 weeks) high temperature exposure. High temperature challenges significantly
      elevated body temperature of experimental birds (P<0.05). However, oxidation
      status of lipid and protein and expression of heat shock transcription factors
      (HSFs) and heat shock proteins (HSPs) 70 and 90 were differently affected by
      acute and chronic treatment. Tissue-specific responses to thermal challenge were
      also found among heart, liver and muscle. In the heart, acute heat challenge
      affected lipid oxidation (P = 0.05) and gene expression of all 4 HSF gene
      expression was upregulated (P<0.05). During chronic heat treatment, the HSP 70
      mRNA level was increased (P<0.05) and HSP 90 mRNA (P<0.05) was decreased. In the
      liver, oxidation of protein was alleviated during acute heat challenge (P<0.05),
      however, gene expression HSF2, 3 and 4 and HSP 70 were highly induced (P<0.05).
      HSP90 expression was increased by chronic thermal treatment (P<0.05). In the
      muscle, both types of heat stress increased protein oxidation, but HSFs and HSPs
      gene expression remained unaltered. Only tendencies to increase were observed in
      HSP 70 (P = 0.052) and 90 (P = 0.054) gene expression after acute heat stress.
      The differential expressions of HSF and HSP genes in different tissues of laying
      broiler breeder chickens suggested that anti-heat stress mechanisms might be
      provoked more profoundly in the heart, by which the muscle was least protected
      during heat stress. In addition to HSP, HSFs gene expression could be used as a
      marker during acute heat stress. 

PMID- 25072283
TI  - Polarization of the vacuolar adenosine triphosphatase delineates a transition to
      high-grade pancreatic intraepithelial neoplasm lesions.
AB  - OBJECTIVES: A functional vacuolar adenosine triphosphatase (v-ATPase) complex
      regulates canonical Wnt/beta-catenin signaling. The goal of this study was to
      identify the distribution of the v-ATPase in human and murine models of
      pancreatic intraepithelial neoplasms (PanINs) and assess its role in Wnt/beta
      catenin signaling. METHODS: We evaluated the immunolabeling pattern of the v
      ATPase in human PanIN specimens and murine PanIN-1 and PanIN-2 lesions obtained
      from Ptf1a(Cre/+); LSL-Kras(G12D) mice. Wnt/beta-catenin signaling was
      interrogated in primary PanIN cells by examining the phosphorylated levels of its
      surface coreceptor, low-density lipoprotein receptor-related protein-6 (LRP6),
      and its intracellular effector, nonphosphorylated beta-catenin. The response of
      primary PanIN cells to epidermal growth factor (EGF) was assessed in the absence
      and presence of the v-ATPase inhibitor, concanamycin. RESULTS: In advanced (PanIN
      2), but not early (PanIN-1), lesions, the v-ATPase assumed a polarized phenotype.
      Blocking the v-ATPase disrupted Wnt/beta-catenin signaling in primary PanIN cells
      despite significantly higher levels of the total and activated Wnt cell surface
      coreceptor, LRP6. Vacuolar adenosine triphosphatase blockade significantly
      decreased the total and activated levels of EGF receptor, a determinant of PanIN
      progression. The activation of EGF receptor and its intracellular mediator,
      p44/42 mitogen-activated protein kinase, was also reduced by v-ATPase blockade.
      This led to diminished proliferation in response to EGF ligand. CONCLUSIONS: The
      v-ATPase regulates Wnt/beta-catenin and EGF receptor signaling in PanINs.

PMID- 25072284
TI  - Type I Interferon Receptor Expression in Human Pancreatic and Periampullary
      Cancer Tissue.
AB  - OBJECTIVES: Interferons (IFNs) have several anticancer mechanisms. A number of
      clinical trials have been conducted regarding adjuvant IFN-alpha therapy in
      pancreatic cancer. Type I IFNs exert their effect via the type I IFN receptor
      (IFNAR-1, IFNAR-2c). The aims of the present study were to determine the type I
      IFN receptor expression in pancreatic and periampullary cancer tissues and to
      study its relation with clinicopathological factors. METHODS: Receptor expression
      was determined by immunohistochemistry in paraffin-embedded cancer tissue of 47
      pancreatic and 54 periampullary cancer patients. RESULTS: The results
      demonstrated that 91.5% of the pancreatic tumors and 88.9% of the periampullary
      tumors showed expression of IFNAR-1, of which 23.4% and 13.0% were strongly
      positive, respectively. Regarding IFNAR-2c expression, 68.1% of the pancreatic
      tumors and 68.5% of the periampullary tumors were positive, of which 4.3% of the
      pancreatic tumors and none of the periampullary tumors had a strong expression.
      No statistically significant associations were found between type I IFN receptor
      expression and clinicopathological factors or survival. CONCLUSIONS: Type I IFN
      receptors are expressed in pancreatic and periampullary cancer tissues although
      with great intertumoral and intratumoral variability. A small proportion of both
      tumors showed a strong expression of the IFNAR-1; only a very small percentage of
      the pancreatic tumors showed strong expression of the IFNAR-2c.

PMID- 25072285
TI  - Sleep disturbance after fracture is related to emotional well-being rather than
      functional result.
AB  - OBJECTIVES: The aim of this study was to investigate the rate, longitudinal
      improvement, and risk factors of sleep disturbance after 4 common orthopaedic
      traumatic conditions. METHODS: The functional status of 1095 patients was
      prospectively assessed using validated questionnaires for patients with acute
      proximal humerus (n = 111), distal radius (n = 440), tibial plateau (n = 109),
      and ankle fractures (n = 435). Patient reported sleep difficulty was compared
      with the overall functional and emotional status of each patient at 3, 6, and 12
      months after treatment. RESULTS: Sleep difficulty at 3-month follow-up was
      reported in 41% of patients with proximal humerus fracture, 25% of patients with
      distal radius fracture, 36% of patients with tibial plateau, and 19% of patients
      with ankle fracture. By 12-month follow-up, less than 20% of patients with all
      fracture types reported sleep difficulty. At 12-month follow-up, the SF-36 Mental
      Health category for patients with distal radius fractures (P = 0.001) and the
      Short Musculoskeletal Function Assessment Emotional category for patients with
      tibial plateau fractures (P = 0.024) and ankle fractures (P <= 0.001) were
      independent predictors of poor sleep, whereas the respective functional status
      categories were not. CONCLUSIONS: At 12-month follow-up, poor sleep was
      independently associated with poor emotional status but not associated with poor
      functional status. The mental health status of patients with sleep difficulty in
      the latter stages of fracture healing should be carefully assessed to provide the
      highest level of care. The results of this study should allow orthopaedic trauma
      surgeons to counsel patients regarding expectations of difficulty sleeping after
      acute fractures. LEVEL OF EVIDENCE: Prognostic level II. See Instructions for
      authors for a complete description of levels of evidence.

PMID- 25072286
TI  - Strategies for surgical approaches in open reduction internal fixation of pilon
      fractures.
AB  - Pilon or tibial plafond fractures usually result from high-energy injuries with
      rotation and/or axial compression. They occur in an area of relatively poor soft
      tissue coverage and frequently present a surgical challenge in deciding which
      incisions will be best for performing open reduction internal fixation. A variety
      of anterior and posterior approaches have been described based on the ease of
      fracture reduction and internal fixation with plates. Some of the incisions are
      fracture specific, that is, planned for a limited approach to the pilon. But in
      more complex cases, a wider exposure is indicated and thus more extensile
      approaches, both anterior and posterior, can be valuable. This review article
      will describe the different surgical approaches, focusing on their indication and
      technique.

PMID- 25072287
TI  - Biomechanical analysis of augmented plate fixation for the treatment of vertical
      shear femoral neck fractures.
AB  - OBJECTIVES: To compare the strength of augmented versus nonaugmented fixation
      techniques for stabilizing vertical shear femoral neck fractures. METHODS: Two
      surgical screw constructs were tested with and without augmentation using 40
      composite femurs: (1) 7.3-mm cannulated screws placed in an inverted triangular
      configuration and (2) 135-degree dynamic hip screw (DHS). The augmentation
      consisted of a 2.7-mm locking plate placed on the anterior-inferior femoral neck.
      Specimens in all 4 groups were tested with load to failure, while failure loads,
      energy absorbed to failure, and axial stiffness were determined. These data were
      then analyzed using a two-way (construct * augmentation) analysis of variance.
      RESULTS: There was no statistically significant interaction between screw
      construct and augmentation for load to failure (P = 0.11). Augmentation with the
      2.7-mm locking plate increased failure loads in both constructs on average by 83%
      (2409 vs. 4417 N, P < 0.01). Femurs instrumented with cannulated screws had 26%
      higher loads to failure than those instrumented with DHS (3879 vs. 3087 N, P <
      0.01). On average, the augmentation increased energy absorbed to failure by 183%
      and constructs' stiffness by 35%. CONCLUSIONS: The strength of surgical repairs
      of the vertical shear femoral neck fractures can be significantly augmented with
      the 2.7-mm locking plate. The construct with the cannulated screws was
      significantly stronger than the DHS construct.

PMID- 25072288
TI  - Effect of distal interlocking screw number and position after intramedullary
      nailing of distal tibial fractures: a biomechanical study simulating immediate
      weight-bearing.
AB  - OBJECTIVE: To quantify the changes in biomechanical stability conferred by the
      addition of a single medial blocking screw or a single bicortical interlocking
      screw to 2 existing distal points of screw fixation in a distal tibial fracture
      model repaired with intramedullary nailing. METHODS: After simulation of a distal
      tibial metaphyseal fracture, 21 synthetic tibiae were repaired with an
      intramedullary nail and: (1) two bicortical locking screws placed in the 2 most
      distal screw holes (IM-L2); (2) three distal bicortical locking screws (IM-L3);
      and 2 distal locking screws and a single blocking screw positioned in the
      sagittal plane on the medial aspect of the nail (IM-L2B). The specimens were
      tested under combined cyclic axial and torsional loading for up to 16k cycles.
      The former was stepwise increasing, whereas the latter was with constant
      amplitude in internal rotation. RESULTS: All constructs survived 12k cycles
      without hardware deformation or failure. IM-L3 constructs displayed the highest
      baseline axial stiffness at the beginning of the test (1130.9 +/- 246.9 N/mm),
      which was significant compared with the IM-L2 construct (701.8 +/- 189.57 N/mm, P
      = 0.004). No significant difference in baseline axial stiffness was identified
      between the IM-L3 and IM-L2B constructs (881.1 +/- 182.4 N/mm, P = 0.125).
      Relative varus interfragmentary deformation at baseline was smaller in the IM-L3
      treatment group (1.3 +/- 0.3 degrees) relative to the IM-L2 group (2.4 +/- 0.7
      degrees, P = 0.012). No differences in torsional rigidity or relative
      interfragmentary torsional deformation were identified between groups (P >
      0.168). Failure was breakage or backout of the distal bicortical screws, fracture
      of the distal fragment, or proximal screw breakage. There was no significant
      difference in number of cycles to failure between instrumentation groups (IM-L2:
      14,345 +/- 1438 cycles; IM-L3: 15,634 +/- 626 cycles; and IM-L2B: 14,862 +/- 1511
      cycles, P = 0.184). CONCLUSION: Results suggest that each of the constructs
      tested here may be a biomechanically viable option allowing for immediate weight
      bearing after fixation of fractures of the distal third of the tibia. The
      addition of a single bicortical interlocking screw to create 3 points of distal
      fixation improves construct stiffness while reducing interfragmentary motion
      relative to 2 interlocking points of screw fixation with or without a blocking
      screw.

PMID- 25072289
TI  - Comparison of SIGN Pediatric and Fin nails in pediatric diaphyseal femur
      fractures: early clinical results.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effectiveness of SIGN
      Pediatric and Fin nails in treating pediatric diaphyseal femur fractures. DESIGN:
      Prospective case series. SETTING: Level I trauma center from 2010 to 2013.
      PATIENT/PARTICIPANTS: Eighteen patients (13 male and 5 female) with pediatric
      diaphyseal femur fractures who did not achieve skeletal maturity. INTERVENTION:
      Femoral nailing was done using either SIGN Pediatric or Fin nail with hand
      reaming without using bone-grafting or image intensifier. MAIN OUTCOME
      MEASUREMENTS: Patients were evaluated for infection, radiographic parameters,
      range of movements, time to weight-bearing (partial and complete), revision
      surgery (if needed), and complications. RESULTS: The average age of patients was
      10.2 (+/-2.1) (range: 6-13) years and average time between injury and surgery was
      13 (1-112) days. Fin nail was used in 13 patients, and Pediatric nail in 5
      patients. There were no infections in either group. The average time for full
      weight-bearing was 7.07 weeks in the Fin nail group, and 8.4 weeks in the
      Pediatric nail group. No repeat surgeries were performed, and there was no case
      of avascular necrosis of femur head, limb length discrepancy, or any other
      complication. CONCLUSIONS: SIGN Pediatric and Fin nails are an effective
      treatment modality for pediatric diaphyseal femur fractures with excellent
      fracture healing with no major complications. LEVEL OF EVIDENCE: Therapeutic
      Level IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25072290
TI  - Single provider reduction and splinting of displaced ankle fractures: a
      modification of Quigley's classic technique.
AB  - Ankle fractures are commonly treated by orthopaedic surgeons and often require
      manipulative reduction. This can be painful for the patient and frequently uses 2
      or more providers. Intra-articular injection of local anesthetic into the ankle
      joint precludes the need for conscious sedation (intravenous narcotics and
      benzodiazepines, propofol, or ketamine). By combining an ankle block with a
      modification of the classic ankle fracture reduction technique described by
      Quigley 1959, a single provider can effectively perform a manipulative reduction
      and splinting of an ankle fracture without conscious sedation.

PMID- 25072291
TI  - ASA score as a predictor of 30-day perioperative readmission in patients with
      orthopaedic trauma injuries: an NSQIP analysis.
AB  - OBJECTIVE: Our purpose was to identify the impact of the physical status of the
      American Society of Anesthesiologists (ASA) on the 30-day readmission of patients
      receiving operative management of orthopaedic fractures using the National
      Surgical Quality Improvement Program (NSQIP) database. METHODS: We analyzed all
      patients with orthopaedic trauma injuries in the American College of Surgeons
      NSQIP database from 2005 to 2011. A total of 8761 patients representing 91
      orthopaedic trauma procedures were identified and included in analysis after
      selection. Logistic regressions were conducted to identify the predictive ability
      of ASA on the likelihood of readmission for patients in each anatomic category
      (upper extremity, pelvis/acetabulum, lower extremity) and the combined study
      population. RESULTS: The ASA physical status proved the strongest predictor of 30
      day readmission for the selected orthopaedic trauma procedures. After controlling
      for age, gender, race, and medical comorbidities that were shown to be
      significant independent risk factors for readmission, ASA score continued to have
      a significant association on 30-day readmissions in the combined population (odds
      ratio = 1.45, 95% confidence interval = 1.13-1.88, P = 0.001). For the combined
      analysis, compared with patients with an ASA score of 1, patients with an ASA
      score of 2 were 1.04 times as likely to have a readmission (P = 0.001), patients
      with an ASA score of 3 were 3.77 times as likely to have a readmission (P =
      0.001), and patients with an ASA score of 4 were 13.7 times as likely to have a
      readmission (P = 0.001). CONCLUSIONS: ASA classification is an indicator for
      variance in readmission for patients receiving operative treatment of orthopaedic
      fractures. Given that ASA classification is a universally collected data point,
      this method can be used in almost any hospital system and for any operative
      service. This model may be used to more accurately predict a patient's
      postoperative course and the expected risk for readmission, such that hospitals
      can target these "at-risk" individuals and reduce 30-day readmissions. LEVEL OF
      EVIDENCE: Prognostic level II. See Instructions for authors for a complete
      description of levels of evidence.

PMID- 25072292
TI  - Cyclic kinetics during thermal equilibration of an axially chiral bis-spiropyran.
AB  - A compound combining the features of a molecular rotor and a photoswitch was
      synthesized and was shown to exist as three diastereomers, which interconvert via
      a reversible cyclic reaction scheme. Each of the three diastereomers was
      isolated, and by following the equilibration kinetics, activation barriers for
      all reactions were calculated. The results indicate that the properties of
      molecular switches depend heavily on their immediate chemical environment. The
      conclusions are important in the context of designing new switchable molecules
      and materials. 

PMID- 25072294
TI  - Mechanistic insights into electrocatalytic CO2 reduction within
      [Ru(II)(tpy)(NN)X]n+ architectures.
AB  - A series of Ru(II)-polypyridyl complexes of the design [Ru(II)(tpy)(NN)X](n+)
      (tpy = 2,2':6',2''-terpyridine; NN = bidentate polypyridine; X = Cl(-) or CH3CN;
      n = 1 or 2) have been synthesized and analyzed for their ability to function as
      electrocatalysts in the reduction of CO2 to CO. Varying the electron
      donating/withdrawing character of the NN polypyridyl ligand has allowed for
      modification of electron density at the formally Ru(II) metal center. Complexes
      where X = Cl(-) display ligand substitution for CH3CN with differing rates of Cl(
      ) dissociation (k-Cl), therefore providing a degree of insight into the electron
      density and thus the chemical activity at the Ru(II) center. Detailed analysis of
      the cyclic voltammograms under argon vs. CO2 atmospheres using multiple switching
      potentials and scan rates ranging from nu = 25-2000 mV s(-1) has painted a
      picture of how monodentate ligand lability due to NN polypyridyl electron
      donating character is related to electrocatalytic CO2 reduction activity of
      Ru(II)-polypyridyl complexes. From these studies, multiple mechanistic pathways
      towards generating the catalytically active [Ru(tpy(-))(NN(-))CO2](0) species are
      proposed and differ via the order of electrochemical and chemical processes. 

PMID- 25072293
TI  - An Abp1-dependent route of endocytosis functions when the classical endocytic
      pathway in yeast is inhibited.
AB  - Clathrin-mediated endocytosis (CME) is a well characterized pathway in both yeast
      and mammalian cells. An increasing number of alternative endocytic pathways have
      now been described in mammalian cells that can be both clathrin, actin, and Arf6-
      dependent or independent. In yeast, a single clathrin-mediated pathway has been
      characterized in detail. However, disruption of this pathway in many mutant
      strains indicates that other uptake pathways might exist, at least for bulk lipid
      and fluid internalization. Using a combination of genetics and live cell imaging,
      here we show evidence for a novel endocytic pathway in S. cerevisiae that does
      not involve several of the proteins previously shown to be associated with the
      'classic' pathway of endocytosis. This alternative pathway functions in the
      presence of low levels of the actin-disrupting drug latrunculin-A which inhibits
      movement of the proteins Sla1, Sla2, and Sac6, and is independent of dynamin
      function. We reveal that in the absence of the 'classic' pathway, the actin
      binding protein Abp1 is now essential for bulk endocytosis. This novel pathway
      appears to be distinct from another described alternative endocytic route in S.
      cerevisiae as it involves at least some proteins known to be associated with
      cortical actin patches rather than being mediated at formin-dependent endocytic
      sites. These data indicate that cells have the capacity to use overlapping sets
      of components to facilitate endocytosis under a range of conditions. 

PMID- 25072295
TI  - Limited knowledge of concussion symptoms in college athletes.
AB  - Concussions are common in athletes and often go unreported. A likely contributor
      to underreporting of concussions in athletes is lack of knowledge of concussion
      related symptoms. The current study assessed concussion symptom knowledge in 382
      Division I athletes and 230 nonathletes. Participants were asked to identify
      potential symptoms following a concussion from a list of both real symptoms and
      distractors. Student-athletes expected significantly more total symptoms
      following a concussion than did nonathletes, and they correctly identified
      symptoms such as nausea and/or vomiting and being easily upset by loud noises
      more frequently than controls. However, many student-athletes failed to identify
      possible emotional symptoms resulting from a concussion, and approximately 70% of
      student-athletes endorsed the distracter item "forgetting names or faces of
      people you know well" as being a symptom of concussion. These current findings
      suggest that student-athletes may have an incomplete understanding of concussion
      related symptoms, and future studies are needed to determine whether formal
      education sessions can improve knowledge for this high-risk population. 

PMID- 25072296
TI  - Personality predicts social dominance in male domestic fowl.
AB  - Individuals in social species commonly form dominance relationships, where
      dominant individuals enjoy greater access to resources compared to subordinates.
      A range of factors such as sex, age, body size and prior experiences has to
      varying degrees been observed to affect the social status an individual obtains.
      Recent work on animal personality (i.e. consistent variation in behavioural
      responses of individuals) demonstrates that personality can co-vary with social
      status, suggesting that also behavioural variation can play an important role in
      establishment of status. We investigated whether personality could predict the
      outcome of duels between pairs of morphologically matched male domestic fowl
      (Gallus gallus domesticus), a species where individuals readily form social
      hierarchies. We found that males that more quickly explored a novel arena, or
      remained vigilant for a longer period following the playback of a warning call
      were more likely to obtain a dominant position. These traits were uncorrelated to
      each other and were also uncorrelated to aggression during the initial part of
      the dominance-determining duel. Our results indicate that several behavioural
      traits independently play a role in the establishment of social status, which in
      turn can have implications for the reproductive success of different personality
      types. 

PMID- 25072297
TI  - The spindle matrix protein, Chromator, is a novel tubulin binding protein that
      can interact with both microtubules and free tubulin.
AB  - The chromodomain protein, Chromator, is localized to chromosomes during
      interphase; however, during cell division together with other nuclear proteins
      Chromator redistributes to form a macro molecular spindle matrix complex that
      embeds the microtubule spindle apparatus. It has been demonstrated that the CTD
      of Chromator is sufficient for localization to the spindle matrix and that
      expression of this domain alone could partially rescue Chro mutant microtubule
      spindle defects. Furthermore, the presence of frayed and unstable microtubule
      spindles during mitosis after Chromator RNAi depletion in S2 cells indicated that
      Chromator may interact with microtubules. In this study using a variety of
      biochemical assays we have tested this hypothesis and show that Chromator not
      only has binding activity to microtubules with a Kd of 0.23 uM but also to free
      tubulin. Furthermore, we have mapped the interaction with microtubules to a
      relatively small stretch of 139 amino acids in the carboxy-terminal region of
      Chromator. This sequence is likely to contain a novel microtubule binding
      interface since database searches did not find any sequence matches with known
      microtubule binding motifs. 

PMID- 25072298
TI  - Quantifying evapotranspiration from urban green roofs: a comparison of chamber
      measurements with commonly used predictive methods.
AB  - Quantifying green roof evapotranspiration (ET) in urban climates is important for
      assessing environmental benefits, including stormwater runoff attenuation and
      urban heat island mitigation. In this study, a dynamic chamber method was
      developed to quantify ET on two extensive green roofs located in New York City,
      NY. Hourly chamber measurements taken from July 2009 to December 2009 and April
      2012 to October 2013 illustrate both diurnal and seasonal variations in ET.
      Observed monthly total ET depth ranged from 0.22 cm in winter to 15.36 cm in
      summer. Chamber results were compared to two predictive methods for estimating
      ET; namely the Penman-based ASCE Standardized Reference Evapotranspiration (ASCE
      RET) equation, and an energy balance model, both parametrized using on-site
      environmental conditions. Dynamic chamber ET results were similar to ASCE RET
      estimates; however, the ASCE RET equation overestimated bottommost ET values
      during the winter months, and underestimated peak ET values during the summer
      months. The energy balance method was shown to underestimate ET compared the ASCE
      RET equation. The work highlights the utility of the chamber method for
      quantifying green roof evapotranspiration and indicates green roof ET might be
      better estimated by Penman-based evapotranspiration equations than energy balance
      methods. 

PMID- 25072299
TI  - Evaluating universal education and screening for postpartum depression using
      population-based data.
AB  - BACKGROUND: In 2006, New Jersey was the first state to mandate prenatal education
      and screening at hospital delivery for postpartum depression. We sought to
      evaluate provision of prenatal education and screening at delivery, estimate the
      prevalence of postpartum depressive symptoms, and identify venues where
      additional screening and education could occur. METHODS: For women who delivered
      live infants during 2009 and 2010 in New Jersey, data on Edinburgh Postnatal
      Depression Scale scores assessed at hospital delivery and recorded on birth
      records were linked to survey data from the Pregnancy Risk Assessment Monitoring
      System (PRAMS), a population-based survey of mothers completed 2-8 months
      postpartum (n=2,391). The PRAMS survey assesses postpartum depressive symptoms
      and whether the woman's prenatal care provider discussed the signs and symptoms
      of perinatal depression with her, used as a proxy for prenatal education on
      depression. RESULTS: Two-thirds (67.0%) of women reported that a prenatal care
      provider discussed depression with them and 89.6% were screened for depression at
      hospital delivery. Among the 13% of women with depressive symptoms at hospital
      delivery or later in the postpartum period, over a third were Women, Infants, and
      Children program (WIC) participants, 13% to 32% had an infant in the neonatal
      intensive care unit (NICU), over 80% attended the maternal postpartum check-up,
      and over 88% of their infants attended >=1 well baby visits. CONCLUSIONS:
      Prenatal education and screening for depression at hospital delivery is feasible
      and results in the majority of women being educated and screened. However, missed
      opportunities for education and screening exist. More information is needed on
      how to utilize WIC, NICU, and well baby and postpartum encounters to ensure
      effective education, accurate diagnosis, and treatment for depressed mothers.

PMID- 25072300
TI  - High resolution mapping of oxygen reduction reaction kinetics at polycrystalline
      platinum electrodes.
AB  - The scanning droplet-based technique, scanning electrochemical cell microscopy
      (SECCM), combined with electron backscatter diffraction (EBSD), is demonstrated
      as a powerful approach for visualizing surface structure effects on the rate of
      the oxygen reduction reaction (ORR) at polycrystalline platinum electrodes.
      Elucidating the effect of electrode structure on the ORR is of major interest in
      connection to electrocatalysis for energy-related applications. The attributes of
      the approach herein stem from: (i) the ease with which the polycrystalline
      substrate electrode can be prepared; (ii) the wide range of surface character
      open to study; (iii) the possibility of mapping reactivity within a particular
      facet (or grain), in a pseudo-single-crystal approach, and acquiring a high
      volume of data as a consequence; (iv) the ready ability to measure the activity
      at grain boundaries; and (v) an experimental arrangement (SECCM) that mimics the
      three-phase boundary in low temperature fuel cells. The kinetics of the ORR was
      analyzed and a finite element method model was developed to explore the effect of
      the three-phase boundary, in particular to examine pH variations in the droplet
      and the differential transport rates of the reactants and products. We have found
      a significant variation of activity across the platinum substrate, inherently
      linked to the crystallographic orientation, but do not detect any enhanced
      activity at grain boundaries. Grains with (111) and (100) contributions exhibit
      considerably higher activity than those with (110) and (100) contributions. These
      results, which can be explained by reference to previous single-crystal
      measurements, enhance our understanding of ORR structure-activity relationships
      on complex high-index platinum surfaces, and further demonstrate the power of
      high resolution flux imaging techniques to visualize and understand complex
      electrocatalyst materials. 

PMID- 25072301
TI  - Urban development in Sub-Saharan Africa: bearer of goods and risks.

PMID- 25072302
TI  - Erythropoiesis-stimulating agents and quality of life: personal journeys of a
      cancer survivor, oncologist, and two cancer health services researchers.

PMID- 25072303
TI  - A proposed new method for assessing the pathological response to chemotherapy in
      resected colorectal liver metastases.
AB  - BACKGROUND: Pathological response (PR) to preoperative chemotherapy for
      colorectal liver metastases (CLM) is recognised as a prognostic factor of
      outcome. However, the optimal system to assess this parameter is still debated.
      This study focuses on current methods and proposes a possibly better method for
      assessing PR. METHODS: Among 223 patients resected for CLM between 2004 and 2011,
      after more than three cycles of chemotherapy, the percentage of tumour cells,
      necrosis and fibrosis, and the tumour regression grade were assessed for each of
      802 nodules. Pathological response was evaluated according to validated methods
      and their combinations. A new method combined the percentage of tumour cells and
      the size of all nodules as follows: , where n is each separate nodule, % is the
      percentage of remaining tumour cells within nodule n (%) and s is the size of
      nodule n (cm).The prognostic value of each method was calculated. RESULTS: After
      a median follow-up of 47 months (3-106), the cumulative 5-year overall survival
      rate after liver resection was 59%. The proposed method categorised as follows: 0
      residual tumour; 0.1-6-cm residual tumour; >6-cm residual tumour, and necrosis
      rate >50% stratified prognosis (P=0.0027; P=0.02), while the other methods did
      not. At multivariate analysis, our method remained an independent predictor of
      outcome (P=0.001). CONCLUSIONS: Combining the percentage of tumour cells
      multiplied by the size of each separate tumour seems to be a better method for
      assessing PR. External validation is required.

PMID- 25072304
TI  - Informed choice of entering medical school and academic success in Iranian
      medical students.
AB  - BACKGROUND: One of the challenges medical education policy-makers confront is
      matriculants' informed choice of entering medicine. However, students' reasons
      for choosing medicine do not seem rational. AIM: We compared students who made an
      informed choice about entering medicine with those who did not, in terms of
      academic success. METHODS: The study was carried out with a self-administered
      questionnaire on 220 final-year medical students randomly selected from six
      Iranian medical schools. Depending on their informed choice of entering medicine
      or not at the time of application, they were divided into two groups. We compared
      these two groups' academic achievement as well as their satisfaction with
      medicine. RESULTS: The students who had not made an informed choice had a higher
      tendency not to choose medicine if they were to start over (p value <=0.001). The
      pre-admission scores of students who had made an informed choice of medicine were
      worse than the other group (p = 0.03). However, their final year scores as well
      as their satisfaction with medicine were higher than the other group.
      CONCLUSIONS: Idealistic views of medicine should be replaced by rational and
      logical ones to help students select the careers best suited to their abilities
      and talents.

PMID- 25072305
TI  - Life-long correction of hyperbilirubinemia with a neonatal liver-specific AAV
      mediated gene transfer in a lethal mouse model of Crigler-Najjar Syndrome.
AB  - Null mutations in the UGT1A1 gene result in Crigler-Najjar syndrome type I
      (CNSI), characterized by severe hyperbilirubinemia and constant risk of
      developing neurological damage. Phototherapy treatment lowers plasma bilirubin
      levels, but its efficacy is limited and liver transplantation is required. To
      find alternative therapies, we applied AAV liver-specific gene therapy to a
      lethal mouse model of CNSI. We demonstrated that a single neonatal hUGT1A1 gene
      transfer was successful and the therapeutic effect lasted up to 17 months
      postinjection. The therapeutic effect was mediated by the presence of
      transcriptionally active double-stranded episomes. We also compared the efficacy
      of two different gene therapy approaches: liver versus skeletal muscle transgene
      expression. We observed that 5-8% of normal liver expression and activity levels
      were sufficient to significantly reduce bilirubin levels and maintain lifelong
      low plasma bilirubin concentration (3.1+/-1.5 mg/dl). In contrast, skeletal
      muscle was not able to efficiently lower bilirubin (6.4+/-2.0 mg/dl), despite 20
      30% of hUgt1a1 expression levels, compared with normal liver. We propose that
      this remarkable difference in gene therapy efficacy could be related to the
      absence of the Mrp2 and Mrp3 transporters of conjugated bilirubin in muscle.
      Taken together, our data support the concept that liver is the best organ for
      efficient and long-term CNSI gene therapy, and suggest that the use of extra
      hepatic tissues should be coupled to the presence of bilirubin transporters.

PMID- 25072306
TI  - Using focus groups in medical education research: AMEE Guide No. 91.
AB  - Qualitative research methodology has become an established part of the medical
      education research field. A very popular data-collection technique used in
      qualitative research is the "focus group". Focus groups in this Guide are defined
      as "... group discussions organized to explore a specific set of issues ... The
      group is focused in the sense that it involves some kind of collective activity
      ... crucially, focus groups are distinguished from the broader category of group
      interview by the explicit use of the group interaction as research data"
      (Kitzinger 1994, p. 103). This Guide has been designed to provide people who are
      interested in using focus groups with the information and tools to organize,
      conduct, analyze and publish sound focus group research within a broader
      understanding of the background and theoretical grounding of the focus group
      method. The Guide is organized as follows: Firstly, to describe the evolution of
      the focus group in the social sciences research domain. Secondly, to describe the
      paradigmatic fit of focus groups within qualitative research approaches in the
      field of medical education. After defining, the nature of focus groups and when,
      and when not, to use them, the Guide takes on a more practical approach, taking
      the reader through the various steps that need to be taken in conducting
      effective focus group research. Finally, the Guide finishes with practical hints
      towards writing up a focus group study for publication.

PMID- 25072308
TI  - Target-triggered three-way junction structure and polymerase/nicking enzyme
      synergetic isothermal quadratic DNA machine for highly specific, one-step, and
      rapid microRNA detection at attomolar level.
AB  - MicroRNAs (miRNAs) play important roles in many biological processes and are
      regarded as promising cancer biomarkers. Herein, a highly specific, one-step, and
      rapid miRNAs detection strategy with attomolar sensitivity has been developed on
      the basis of a target-triggered three-way junction (3-WJ) structure and
      polymerase/nicking enzyme synergetic isothermal quadratic DNA machine (ESQM). To
      this end, 3-WJ probes (primer and template) are designed to selectively recognize
      target miRNA and form the stable 3-WJ structure to trigger ESQM, resulting in a
      high quadratic amplified signal. A high specificity is demonstrated by the
      excellent discrimination of even single-base mismatched homologous sequences with
      mismatched bases in varied locations (close to the 3'-end, the 5'-end, and the
      middle). In addition, a low detection limit down to 2 amol was achieved within 30
      min. This sensitivity is much higher than those of most linear amplification
      based approaches and is even comparable to those of some exponential
      amplification-based methods. Furthermore, the applicability of this method in
      complex samples was demonstrated by the analysis of cancer cell small RNA
      extracts, results of which were in good agreement with those obtained by a
      commercial miRNA kit and previously published data. The miRNA with a 3' end
      modification (2'-O-methylation), such as plant miRNA, was also successfully
      detected, confirming the good universality of the proposed strategy. It is
      worthwhile to point out that several well-established methods using miRNA as
      primer for polymerization reaction are of relatively poor performance in the
      analysis of these modified miRNA. Therefore, these merits endow the developed
      strategy with powerful implications for biological research and an effective
      diagnostic assay. 

PMID- 25072307
TI  - Comparison of reduced-intensity and myeloablative conditioning regimens for
      allogeneic hematopoietic stem cell transplantation in patients with acute myeloid
      leukemia and acute lymphoblastic leukemia: a meta-analysis.
AB  - Currently, the indications to perform reduced-intensity conditioning allogeneic
      hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly
      from large registry and single-centre retrospective studies. Thus, at the present
      time, there is limited direct evidence supporting the current practice in
      selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic
      leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To
      determine the relationship between dose intensity of conditioning regimen and
      survival outcomes after allografting in AML/ALL patients, we performed a meta
      analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258
      adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC
      HCT resulted in comparable <2-year and 2-6 year overall survival (OS) rates post
      transplantation even though the RIC-HCT recipients were older and had more active
      disease than MAC-HCT recipients. The 2-6 year progression-free survival (PFS),
      nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD
      rates were reduced after RIC-HCT, but relapse rate was increased. Similar
      outcomes were observed regardless of disease type and status at transplantation.
      Odds ratio for all outcomes remained comparable with or without performing
      separate analyses for the year of HCT and for retrospective versus prospective
      studies. Among RIC-HCT recipients, survival rates were superior if patients were
      in CR at transplantation. Significant inter-study heterogeneity for aGvHD data
      and publication bias for PFS data were observed. This meta-analysis showed no OS
      benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting
      that RIC-HCT could be an effective therapeutic option for AML/ALL patients who
      are ineligible for MAC-HCT and CR status is preferred before RIC-HCT. 

PMID- 25072309
TI  - Better data ? Bigger data.

PMID- 25072310
TI  - Environmentally responsive polymeric materials: effect of the topological
      structure on self-assembly.
AB  - A novel amphiphilic homopolymer (PAGC8), containing two hydrophilic head groups
      and double hydrophobic tails in each repeat unit, has been prepared by solution
      polymerization and named as "a geminized amphiphilic homopolymer" in this paper,
      which is capable of self-assembling into various nanoobjects depending on the
      solution concentration and solvent properties. Characterization of the self
      assembly behaviors was carried out by steady-state fluorescence, transmission
      electron microscopy and nuclear magnetic resonance techniques. Particular
      emphasis was dedicated to the environmental responsiveness of the assemblies. The
      morphologies were observed to transform from micelle-type to vesicles on adding a
      certain amount of ethanol. It is noteworthy that the assemblies were able to trap
      hydrophilic (rhodamine B) and hydrophobic (Sudan Red) molecules. Subsequently
      different nanoobjects were found after the encapsulation. To probe the effect of
      the topological structure on the self-assembly behaviors, the properties of an
      additional homopolymer with single charge pendant architecture on the backbone
      were investigated for comparison. Significant differences in structure between
      the two architectures brought out remarkable variations in aggregates, which were
      non-responsive to the solvent environment, or encapsulation of molecules. Based
      on the experimental results, we proposed a possible mechanism of the
      morphological transitions of the assemblies. 

PMID- 25072311
TI  - Pediatric vascularized composite allotransplantation.
AB  - BACKGROUND: Vascularized composite allotransplantation (VCA) has experienced a
      growing acceptance, which has led to a debate centered on extending the
      indications of the procedure to include pediatric patients. The aim of this
      article was to discuss such indications based on the evidence in pediatric solid
      organ transplantation, reconstructive surgery in children, and VCA in adult
      patients. METHODS: Papers published on the outcomes of pediatric solid organ
      transplantation, growth after replantation of extremities, vascularized
      autologous tissue transfer, craniofacial surgery, orthognathic procedures, facial
      fractures, and outcomes after repair of peripheral nerves in children were
      reviewed. RESULTS: Although the outcomes of solid organ transplantation in
      children have improved, the transplanted organs continue to have a limited
      lifespan. Long-term immunosuppressive therapy exposes the patients to an
      increased lifetime risk of infections, diabetes, hypertension, dyslipidemia,
      cardiovascular disease, and malignancy. Growth impairment and learning
      disabilities are other relevant drawbacks, which affect the pediatric recipients.
      Nonadherence to medication is a common cause of graft dysfunction and loss among
      the adolescent transplant recipients. Rejection episodes, hospitalizations, and
      medication adverse effects contribute negatively to the quality of life of the
      patients. Although normal growth after limb transplantation could be expected,
      pediatric facial transplant recipients may present with arrest of growth of
      transplanted midfacial skeleton. CONCLUSIONS: Considering the non-life
      threatening nature of the conditions that lead to eligibility for VCA, it is
      suggested that it is premature to extend the indications of VCA to include
      pediatric patients under the currently available immunosuppressive protocols.

PMID- 25072312
TI  - Sciatic and peroneal nerve injuries after endovascular ablation of lower
      extremity varicosities: case reports and review of the literature.
AB  - Varicose veins have traditionally been treated by surgical intervention. When
      performed in the lower limb, surgical vein stripping can potentially cause injury
      to the saphenous, sural, tibial, and peroneal nerves due to anatomic proximity.
      Newer, minimally invasive procedures, such as endovenous laser ablation and
      endovenous radiofrequency ablation, are more commonly used today. Although the
      potential for neural injury is greatly reduced, endovenous laser ablation and
      endovenous radiofrequency ablation have been documented to cause neural damage.
      Here, we report rare complications of 2 cases of varicosity endovascular
      ablation. One case involves ablation of the lesser saphenous vein and resulted in
      injury to the proximal common peroneal and tibial as well as distal sciatic
      nerves. The second case involves ablation of the vein of Giacomini that resulted
      in a common peroneal nerve injury. We stress the importance of preoperative
      anatomic mapping of the highly variable venous and neural systems in the area of
      ablation to minimize neural complications. 

PMID- 25072313
TI  - Immediate re-insertion of non-autologous materials in revision augmentation
      rhinoplasty.
AB  - OBJECTIVE: This paper aims to study whether immediate re-insertion of non
      autologous augmentation material in revision augmentation rhinoplasty is a safe
      surgical strategy creating a successful and functional aesthetic outcome. STUDY
      DESIGN: Retrospective review and analysis of medical records. SETTING: Tertiary
      referral hospital. SUBJECTS AND METHODS: A retrospective analysis of 11
      consecutive patients who had undergone removal of previous augmentation material
      and immediate re-insertion of non-autologous material in revision augmentation
      rhinoplasty was performed. Demographics, surgical approaches, augmentation
      materials, material-related complications, time interval between surgeries,
      surgical outcome, and follow-up period were included in the analysis to evaluate
      our surgical strategy. RESULTS: A successful surgical outcome with respect to
      both functional and aesthetic aspects was obtained in nine of the 11 enrolled
      patients. In 1 patient, there was a recurrence of material-related complication,
      while another patient experienced unsatisfactory graft displacement. The
      unsuccessful cases had 2 common features in that silicone and endonasal
      approaches were used in the primary and revision surgeries, respectively.
      CONCLUSION: Removal of previous augmentation material and immediate re-insertion
      of non-autologous material for dorsal augmentation in revision rhinoplasty is
      feasible with respect to functional and aesthetic aspects of patient outcome.

PMID- 25072315
TI  - Craniopharyngiomas Presenting with Nonobstructive Hydrocephalus: Underlying
      Influence of Subarachnoidal Hemorrhage. Two Case Reports.
AB  - Nonobstructive hydrocephalus in craniopharyngioma patients is rare, and the
      etiology is not known. We report two cases of patients with craniopharyngioma who
      presented with nonobstructive hydrocephalus. Repeated subarachnoidal hemorrhage
      (SAH) was considered as the underlying mechanism of hydrocephalus development.
      The first case was a 67-year-old woman presenting with deteriorated
      consciousness. Head computed tomography (CT) and magnetic resonance (MR) imaging
      demonstrated a solid suprasellar tumor with subarachnoidal and intraventricular
      hematoma with ventricle dilatation but no cerebrospinal fluid (CSF) obstruction.
      The extended transsphenoidal approach achieved gross total removal. Because of
      persistent ventricle dilatation, ventriculoperitoneal shunt was required. The
      second case was a 35-year-old woman presenting with persistent headache. Head CT
      and MR imaging demonstrated a solid suprasellar tumor with ventricular dilatation
      but no CSF obstruction. The extended transsphenoidal approach achieved gross
      total removal. The postoperative course was uneventful, and a
      ventriculoperitoneal shunt was not required. In both cases, histologic
      examination of the tumors revealed squamous-papillary type craniopharyngioma with
      remarkable inflammatory cell infiltrations in the perivascular space. CSF
      cytology revealed hemosiderin-laden phagocytes, indicative of previous SAH
      causing CSF malabsorption. These cases suggested that surgery should be indicated
      for patients with craniopharyngiomas with nonobstructive hydrocephalus, even if
      the tumors are not associated with neurologic and/or endocrinologic deficits. 

PMID- 25072314
TI  - Inhibition of Hsp90 augments docetaxel therapy in castrate resistant prostate
      cancer.
AB  - First line treatment of patients with castrate resistant prostate cancer (CRPC)
      primarily involves administration of docetaxel chemotherapy. Unfortunately,
      resistance to docetaxel therapy is an ultimate occurrence. Alterations in
      androgen receptor (AR) expression and signaling are associated mechanisms
      underlying resistance to docetaxel treatment in CRPC. Heat shock protein 90
      (Hsp90) is a molecular chaperone, which regulates the activation, maturation and
      stability of critical signaling proteins involved in prostate cancer, including
      the AR. This knowledge and recent advances in compound design and development
      have highlighted Hsp90 as an attractive therapeutic target for the treatment of
      CRPC. We recently reported the development of a MYC-CaP castrate resistant (MYC
      CaP/CR) transplant tumor model, which expresses amplified wild type AR. Within,
      we report that a second generation Hsp90 inhibitor, NVP-AUY922, inhibits cell
      growth and significantly induces cell death in MYC-CaP/CR and Pten-CaP/cE2 cell
      lines. NVP-AUY922 induced proteasome degradation of AR, though interestingly does
      not require loss of AR protein to inhibit AR transcriptional activity. Further,
      NVP-AUY922 increased docetaxel toxicity in MYC-CaP/CR and Pten-CaP/cE2 cell lines
      in vitro. Finally, NVP-AUY922/docetaxel combination therapy in mice bearing MYC
      CaP/CR tumors resulted in greater anti-tumor activity compared to single
      treatment. This study demonstrates that NVP-AUY922 elicits potent activity
      towards AR signaling and augments chemotherapy response in a mouse model of CRPC,
      providing rationale for the continued clinical development of Hsp90 inhibitors in
      clinical trials for treatment of CRPC patients. 

PMID- 25072316
TI  - Long-term outcome after adjacent two-level anterior cervical discectomy and
      fusion using stand-alone plasmaphore-covered titanium cages.
AB  - BACKGROUND: Reports on long-term outcome of stand-alone contiguous two-level
      anterior cervical discectomy and fusion (ACDF) using stand-alone Plasmaphore
      coated titanium cages (PCTCs) are rare, and data on follow-ups > 3 years are
      missing. OBJECTIVE: To evaluate the long-term outcome of adjacent two-level
      microsurgical ACDF using stand-alone PCTC. PATIENTS/MATERIAL AND METHODS: A total
      of 33 consecutive patients presented with cervical degenerative disc disease
      (DDD) underwent contiguous two-level ACDF. Clinical long-term evaluation (mean:
      61 +/- 14 months) included documentation of neurologic deficits (motor deficits,
      sensory deficits, reflex status, and gait disturbance), neck pain, and radicular
      pain. Functional outcome was measured using the Odom criteria, patient-perceived
      outcome, and evaluation of work status. Radiographs were evaluated to assess
      intervertebral disc height, subsidence, level of fusion, sagittal balance, and
      implant position. RESULTS: Surgery was performed at levels C5-C6 and C6-C7 in 30
      patients and at C4-C5 and C5-C6 in 3 (mean age: 50.1 +/- 7.7 years). Symptoms and
      neurologic deficits improved as follows: neurologic deficits (pre: 100%; post:
      36%), radicular pain (pre: 85%; post: 15%), and neck pain (pre: 94%; post: 33%).
      Excellent and good functional and subjective outcome was noted in 75%. Cage
      subsidence was found to be more prominent in the lower (52%) than the upper (36%)
      mobile cervical segment. Two-level fusion was documented in most patients (n = 29
      [88%]). Kyphotic deformity occurred in two cases (n = 2 [6%]). CONCLUSIONS: Stand
      alone contiguous two-level ACDF using PCPT proved to be effective, yielding good
      long-term clinical and functional outcomes. The relatively high rate of
      subsidence did not affect the good clinical and functional long-term outcome.

PMID- 25072317
TI  - Survival in granular cell astrocytomas.
AB  - BACKGROUND: Granular cell astrocytomas (GCAs) are rarely encountered aggressive
      glial neoplasms. Treatment options comprise surgery, radiotherapy, and
      chemotherapy. Due to the small number of cases, a standard therapeutic regimen
      for GCA does not exist. MATERIAL AND METHODS: We report on the case of a 64-year
      old woman with GCA subjected to tumor biopsy followed by radiochemotherapy with
      temozolomide. We provide clinical, histopathologic, and magnetic resonance
      imaging findings as well as a complete follow-up. To assess the relation of age,
      gender, time of publication, and different treatment options with survival we
      performed log-rank tests and calculated Cox regression models and hazard ratios
      in data from all available reports on GCA. RESULTS: A significant difference in
      survival rates in favor of adjuvant therapy (radiotherapy or radiochemotherapy)
      at 12 months was found. Age > 70 years at the time of diagnosis had a
      significantly unfavorable impact on survival at 12 months. Although not
      statistically significant, a tendency toward higher probability of survival at 12
      months was found in cases reported after 2002. In surgically treated patients, we
      could not find a significant impact of extent of resection on survival. A
      significant impact of gender on survival was not found. CONCLUSION: Adjuvant
      therapy is significantly related to a higher probability of survival at 12 months
      and may therefore be recommended for patients with a GCA. Further analysis of
      these rare neoplasms is warranted.

PMID- 25072318
TI  - Individual diet has sex-dependent effects on vertebrate gut microbiota.
AB  - Vertebrates harbour diverse communities of symbiotic gut microbes. Host diet is
      known to alter microbiota composition, implying that dietary treatments might
      alleviate diseases arising from altered microbial composition ('dysbiosis').
      However, it remains unclear whether diet effects are general or depend on host
      genotype. Here we show that gut microbiota composition depends on interactions
      between host diet and sex within populations of wild and laboratory fish,
      laboratory mice and humans. Within each of two natural fish populations
      (threespine stickleback and Eurasian perch), among-individual diet variation is
      correlated with individual differences in gut microbiota. However, these diet
      microbiota associations are sex dependent. We document similar sex-specific diet
      microbiota correlations in humans. Experimental diet manipulations in laboratory
      stickleback and mice confirmed that diet affects microbiota differently in males
      versus females. The prevalence of such genotype by environment (sex by diet)
      interactions implies that therapies to treat dysbiosis might have sex-specific
      effects. 

PMID- 25072320
TI  - Autism treatments proposed by clinical studies and human genetics are
      complementary.

PMID- 25072319
TI  - Women with the Alzheimer's risk marker ApoE4 lose Abeta-specific CD4+ T cells 10
      20 years before men.
AB  - Adaptive immunity to self-antigens causes autoimmune disorders, such as multiple
      sclerosis, psoriasis and type 1 diabetes; paradoxically, T- and B-cell responses
      to amyloid-beta (Abeta) reduce Alzheimer's disease (AD)-associated pathology and
      cognitive impairment in mouse models of the disease. The manipulation of adaptive
      immunity has been a promising therapeutic approach for the treatment of AD,
      although vaccine and anti-Abeta antibody approaches have proven difficult in
      patients, thus far. CD4(+) T cells have a central role in regulating adaptive
      immune responses to antigens, and Abeta-specific CD4(+) T cells have been shown
      to reduce AD pathology in mouse models. As these cells may facilitate endogenous
      mechanisms that counter AD, an evaluation of their abundance before and during AD
      could provide important insights. Abeta-CD4see is a new assay developed to
      quantify Abeta-specific CD4(+) T cells in human blood, using dendritic cells
      derived from human pluripotent stem cells. In tests of >50 human subjects Abeta
      CD4see showed an age-dependent decline of Abeta-specific CD4(+) T cells, which
      occurs earlier in women than men. In aggregate, men showed a 50% decline in these
      cells by the age of 70 years, but women reached the same level before the age of
      60 years. Notably, women who carried the AD risk marker apolipoproteinE-E4
      (ApoE4) showed the earliest decline, with a precipitous drop between 45 and 52
      years, when menopause typically begins. Abeta-CD4see requires a standard blood
      draw and provides a minimally invasive approach for assessing changes in Abeta
      biology that may reveal AD-related changes in physiology by a decade.
      Furthermore, CD4see probes can be modified to target any peptide, providing a
      powerful new tool to isolate antigen-specific CD4(+) T cells from human subjects.

PMID- 25072321
TI  - Cerebellar Purkinje cell p75 neurotrophin receptor and autistic behavior.
AB  - The p75 neurotrophin receptor (p75NTR) is normally expressed in cerebellar
      Purkinje cells throughout the lifespan. Children with autism spectrum behavior
      exhibit apparent cerebellar Purkinje cell loss. Cerebellar transcriptome changes
      seen in the murine prenatal valproate exposure model of autism include all of the
      proteins known to constitute the p75NTR interactome. p75NTR is a modulator of
      cytoplasmic and mitochondrial redox potential, and others have suggested that
      aberrant response to oxidant stress has a major role in the pathogenesis of
      autism. We have created Purkinje cell-selective p75NTR knockout mice that are the
      progeny of hemizygous Cre-Purkinje cell protein 2 C57Bl mice and p75NTR floxed
      C57Bl mice. These Cre-loxP mice exhibit complete knockout of p75NTR in ~50% of
      the cerebellar Purkinje cells. Relative to Cre-only mice and wild-type C57Bl
      mice, this results in a behavioral phenotype characterized by less allogrooming
      of (P<0.05; one-way analysis of variance) and socialization or fighting with
      (each P<0.05) other mice; less (1.2-fold) non-ambulatory exploration of their
      environment than wild-type (P<0.01) or Cre only (P<0.01) mice; and almost twofold
      more stereotyped jumping behavior than wild-type (P<0.05) or Cre (P<0.02) mice of
      the same strain. Wild-type mice have more complex dendritic arborization than Cre
      loxP mice, with more neurites per unit area (P<0.025, Student's t-test), more
      perpendicular branches per unit area (P<0.025) and more short branches/long
      neurite (P<0.0005). Aberrant developmental regulation of expression of p75NTR in
      cerebellar Purkinje cells may contribute to the pathogenesis of autism. 

PMID- 25072322
TI  - Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity,
      gray matter volume and brain activity in mammals.
AB  - D-aspartate (D-Asp) is an atypical amino acid, which is especially abundant in
      the developing mammalian brain, and can bind to and activate N-methyl-D-Aspartate
      receptors (NMDARs). In line with its pharmacological features, we find that mice
      chronically treated with D-Asp show enhanced NMDAR-mediated miniature excitatory
      postsynaptic currents and basal cerebral blood volume in fronto-hippocampal
      areas. In addition, we show that both chronic administration of D-Asp and
      deletion of the gene coding for the catabolic enzyme D-aspartate oxidase (DDO)
      trigger plastic modifications of neuronal cytoarchitecture in the prefrontal
      cortex and CA1 subfield of the hippocampus and promote a cytochalasin D-sensitive
      form of synaptic plasticity in adult mouse brains. To translate these findings in
      humans and consistent with the experiments using Ddo gene targeting in animals,
      we performed a hierarchical stepwise translational genetic approach.
      Specifically, we investigated the association of variation in the gene coding for
      DDO with complex human prefrontal phenotypes. We demonstrate that genetic
      variation predicting reduced expression of DDO in postmortem human prefrontal
      cortex is mapped on greater prefrontal gray matter and activity during working
      memory as measured with MRI. In conclusion our results identify novel NMDAR
      dependent effects of D-Asp on plasticity and physiology in rodents, which also
      map to prefrontal phenotypes in humans. 

PMID- 25072323
TI  - Association of aberrant neural synchrony and altered GAD67 expression following
      exposure to maternal immune activation, a risk factor for schizophrenia.
AB  - A failure of integrative processes within the brain, mediated via altered
      GABAergic inhibition, may underlie several features of schizophrenia. The present
      study examined, therefore, whether maternal immune activation (MIA), a risk
      factor for schizophrenia, altered inhibitory markers in the hippocampus and
      medial prefrontal cortex (mPFC), while also altering electroencephalogram (EEG)
      coherence between these regions. Pregnant rats were treated with saline or
      polyinosinic:polycytidylic acid mid-gestation. EEG depth recordings were made
      from the dorsal and ventral hippocampus and mPFC of male adult offspring.
      Glutamic decarboxylase (GAD67) levels were separately assayed in these regions
      using western blot. GAD67 expression was also assessed within parvalbumin
      positive cells in the dorsal and ventral hippocampus using immunofluorescence
      alongside stereological analysis of parvalbumin-positive cell numbers. EEG
      coherence was reduced between the dorsal hippocampus and mPFC, but not the
      ventral hippocampus and mPFC, in MIA animals. Western blot and immunofluorescence
      analyses revealed that GAD67 expression within parvalbumin-positive cells was
      also reduced in the dorsal hippocampus relative to ventral hippocampus in MIA
      animals when compared with controls. This reduction was observed in the absence
      of parvalbumin-positive neuronal loss. Overall, MIA produced a selective
      reduction in EEG coherence between the dorsal hippocampus and mPFC that was
      paralleled by a similarly specific reduction in GAD67 within parvalbumin-positive
      cells of the dorsal hippocampus. These results suggest a link between altered
      inhibitory mechanisms and synchrony and, therefore point to potential mechanisms
      via which a disruption in neurodevelopmental processes might lead to
      pathophysiology associated with schizophrenia. 

PMID- 25072327
TI  - Novel potential targets for prevention of arterial restenosis: insights from the
      pre-clinical research.
AB  - Restenosis is the pathophysiological process occurring in 10-15% of patients
      submitted to revascularization procedures of coronary, carotid and peripheral
      arteries. It can be considered as an excessive healing reaction of the vascular
      wall subjected to arterial/venous bypass graft interposition, endarterectomy or
      angioplasty. The advent of bare metal stents, drug-eluting stents and of the more
      recent drug-eluting balloons, have significantly reduced, but not eliminated, the
      incidence of restenosis, which remains a clinically relevant problem. Biomedical
      research in pre-clinical animal models of (re)stenosis, despite its limitations,
      has contributed enormously to the identification of processes involved in
      restenosis progression, going well beyond the initial dogma of a primarily
      proliferative disease. Although the main molecular and cellular mechanisms
      underlying restenosis have been well described, new signalling molecules and cell
      types controlling the progress of restenosis are continuously being discovered.
      In particular, microRNAs and vascular progenitor cells have recently been shown
      to play a key role in this pathophysiological process. In addition, the advanced
      highly sensitive high-throughput analyses of molecular alterations at the
      transcriptome, proteome and metabolome levels occurring in injured vessels in
      animal models of disease and in human specimens serve as a basis to identify
      novel potential therapeutic targets for restenosis. Molecular analyses are also
      contributing to the identification of reliable circulating biomarkers predictive
      of post-interventional restenosis in patients, which could be potentially helpful
      in the establishment of an early diagnosis and therapy. The present review
      summarizes the most recent and promising therapeutic strategies identified in
      experimental models of (re)stenosis and potentially translatable to patients
      subjected to revascularization procedures.

PMID- 25072328
TI  - Relation between the catalytic efficiency of the synthetic analogues of catechol
      oxidase with their electrochemical property in the free state and substrate-bound
      state.
AB  - A library of 15 dicopper complexes as synthetic analogues of catechol oxidase has
      been synthesized with the aim to determine the relationship between the
      electrochemical behavior of the dicopper(II) species in the absence as well as in
      the presence of 3,5-di-tert-butylcatechol (3,5-DTBC) as model substrate and the
      catalytic activity, kcat, in DMSO medium. The complexes have been characterized
      by routine physicochemical techniques as well as by X-ray single-crystal
      structure analysis in some cases. Fifteen "end-off" compartmental ligands have
      been designed as 1 + 2 Schiff-base condensation product of 2,6-diformyl-4-R
      phenol (R = Me, (t)Bu, and Cl) and five different amines, N-(2
      aminoethyl)piperazine, N-(2-aminoethyl)pyrrolidine, N-(2-aminoethyl)morpholine, N
      (3-aminopropyl)morpholine, and N-(2-aminoethyl)piperidine. Interestingly, in case
      of the combination of 2,6-diformyl-4-methylphenol and N-(2
      aminoethyl)morpholine/N-(3-aminopropyl)morpholine/N-(2-aminoethyl)piperidine 1 +
      1 condensation becomes the reality and the ligands are denoted as L2(1-3). On
      reaction of copper(II) nitrate with L2(1-3) in situ complexes 3, 12, and 13 are
      formed having general formula Cu2(L2(1-3))2(NO3)2. The remaining 12 ligands
      obtained as 1 + 2 condensation products are denoted as L1(1-12), which produce
      complexes having general formula Cu2(L1(1-12))(NO3)2. Catecholase activity of all
      15 complexes has been investigated in DMSO medium using 3,5-DTBC as model
      substrate. Treatment on the basis of Michaelis-Menten model has been applied for
      kinetic study, and thereby turnover number, kcat, values have been evaluated.
      Cyclic voltametric (CV) and differential pulse voltametric (DPV) studies of the
      complexes in the presence as well as in the absence of 3,5-DTBC have been
      thoroughly investigated in DMSO medium. From those studies it is evident that
      oxidation of 3,5-DTBC catalyzed by dicopper(II) complexes proceed via two steps:
      first, semibenzoquinone followed by benzoquinone with concomitant reduction of
      Cu(II) to Cu(I). Our study reveals that apparently there is nearly no linear
      relationship between kcat and E degrees  values of the complexes. However, a
      detailed density functional theory (DFT) calculation sheds light on this subject.
      A very good correlation prevails in terms of the energetics associated with the
      Cu(II) to Cu(I) reduction process and kcat values, as revealed from the combined
      theoretical and experimental approach. 

PMID- 25072326
TI  - Selective androgen receptor modulators (SARMs) negatively regulate triple
      negative breast cancer growth and epithelial:mesenchymal stem cell signaling.
AB  - INTRODUCTION: The androgen receptor (AR) is the most highly expressed steroid
      receptor in breast cancer with 75-95% of estrogen receptor (ER)-positive and 40
      70% of ER-negative breast cancers expressing AR. Though historically breast
      cancers were treated with steroidal androgens, their use fell from favor because
      of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal,
      tissue selective androgen receptor modulators (SARMs) may provide a novel
      targeted approach to exploit the therapeutic benefits of androgen therapy in
      breast cancer. MATERIALS AND METHODS: Since MDA-MB-453 triple-negative breast
      cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast
      cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate
      the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis
      and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were
      performed to understand the mechanisms of action. RESULTS: Dihydrotestosterone
      and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR.
      The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than
      90%, compared to vehicle-treated tumors. SARM treatment inhibited the
      intratumoral expression of genes and pathways that promote breast cancer
      development through its actions on the AR. SARM treatment also inhibited the
      metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration
      and invasion of epithelial:MSC co-cultures. CONCLUSION: 1. AR stimulation
      inhibits paracrine factors that are important for MSC interactions and breast
      cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted
      therapies to treat AR-positive triple-negative breast cancer.

PMID- 25072329
TI  - The revised Code: is it up to the standard we expect?

PMID- 25072330
TI  - Elderly care: reflecting on that ultimate 'never event'.

PMID- 25072331
TI  - Delirium in older people in hospital: an education programme.
AB  - AIM: This study aimed to determine the effectiveness of an educational programme
      on the identification and management of delirium by nurses in the medical wards
      of a tertiary care hospital in South India. METHOD: A non-equivalent controlled
      pre- and post-intervention research design was used. The sample size of nurses
      through convenient sampling was 15 in the experimental group and 17 in the
      comparison group. A questionnaire was used to assess the knowledge of nurses and
      an observation checklist was used to assess practice. The Confusion Assessment
      METHOD ( Inouye et al, 1990 ) was used to detect delirium among older people who
      were hospitalised. Data collection was carried out over a 6-week period. RESULTS:
      There was a significant improvement in the knowledge (p<0.001) and practice
      (p<0.003) of nurses in the experimental group following the educational
      programme.

PMID- 25072332
TI  - Quality of life data in older adults: self-assessment vs interview.
AB  - BACKGROUND AND PURPOSE: There are obstacles for older people when reporting
      quality of life (QoL) in a survey format. The aim of this study was to explore
      the quality of data obtained on self-assessed QoL among older people with respect
      to modes of administration. METHOD AND RESULTS: Approximately half of the QoL
      items showed significantly higher mean values in the mail sample than in the
      interview sample. Data suggest that there may be more vulnerability towards
      offering socially desirable answers. Problems with reduced energy and loss of
      memory affect both modes of administration. CONCLUSIONS: This study demonstrates
      that investigating the mode of questionnaire administration among older people
      can be a valuable means by which to detect possible threats to data quality when
      interpreting QoL scores.

PMID- 25072333
TI  - Effective multidisciplinary working: the key to high-quality care.
AB  - This article explores multidisciplinary team working, inter-disciplinary, trans
      disciplinary and effective collaborative practice in order to provide high
      quality patient care. It discusses different views on collaboration, some of the
      issues around cross-discipline and multi-agency working and concerns around
      promoting 'high-quality' care. It also discusses the importance of evidence-based
      practice in multidisciplinary teams. Issues around good-quality care, clinical
      governance and the audit cycle in MDTs are addressed. The article highlights the
      importance of the 6Cs (care, compassion, competence, communication, courage and
      commitment) in MDTs if quality care is to be achieved. The article also explores
      advantages and limitations of multidisciplinary team working, trans-disciplinary
      working and inter-professional working in developing and delivering high-quality
      patient-centred care. Further research is needed on how clinical audits can help
      to improve how MDTs function in order improve the quality of service provided to
      clients. 

PMID- 25072334
TI  - Challenges in acute care of people with co-morbid mental illness.
AB  - Acute secondary care settings are complex environments that offer a range of
      challenges for healthcare staff. These challenges can be exacerbated when
      patients present with a co-morbid mental illness. This article is a systematic
      review of the literature that has investigated the challenges imposed on health
      professionals working in acute secondary care settings where they care for
      patients who experience co-morbid physical and mental illnesses. A systematic
      search of the bibliographic databases was conducted and a total of 25 articles
      were included in this review. A number of challenges were identified including
      experience of fear, negative attitudes, poor mental health literacy, being
      positive and optimistic in providing care as a profession and environmental
      factors. Health professionals working in acute secondary care settings require
      organisational support and training in mental health care. Acute secondary care
      environments conducive to providing holistic care to patients experiencing mental
      illness co-morbidity are required. 

PMID- 25072335
TI  - The practice of clinical handover: a respite perspective.
AB  - This article aims to reflect on handovers that take place in respite settings-a
      healthcare setting with little mention in the literature. The author presents a
      reflective account of the practice of handover in one respite unit in south-east
      England. As these are the author's own observations and experience, no reflective
      model has been used as a guide. The article also reports on the findings of a
      small web-based survey conducted by Facebook and email contacts that aimed to
      understand the attitudes of health professionals, mainly from the respite-care
      setting, towards the practice of clinical handover. The findings showed that
      handover is an important part of safer care practice and is highly valued by the
      respondents as being a planning and organising mechanism for better management of
      shifts. This paper concludes by raising awareness of the lack of information
      available about the practice of clinical handover in respite settings. It also
      suggests the need for an in-depth study on handover practice in respite care. 

PMID- 25072336
TI  - Pharmacogenomics: the path to individualised patient care.

PMID- 25072337
TI  - Interprofessional education: merging nursing, midwifery and CAM.
AB  - AIM: To ascertain the value of bringing together undergraduate students from
      nursing, midwifery, and complementary and alternative medicine (CAM) to determine
      what they could learn from each other. BACKGROUND: Interprofessional education
      (IPE) is a growing field promoting interaction between professional groups,
      collaborative working and quality of health. In conventional health, IPE has a
      role to play in undergraduate education. No studies have been undertaken to
      investigate the integration of CAM students and conventional undergraduate
      healthcare students. METHOD: In a mixed-method study, in 2010, a sample of third
      year students enrolled on adult nursing, midwifery, homeopathy and complementary
      therapies degree courses took part in two workshops and a focus-group discussion.
      FINDINGS: Six themes were identified from qualitative data analysis: interaction;
      breaking down prejudices; knowledge of self; knowledge of others; common aims;
      and organisational limitations. CONCLUSION: The common aim of patient-centred
      care allowed students to recognise the benefits of a more integrated health
      system.

PMID- 25072338
TI  - Commissioning end-of-life care.

PMID- 25072339
TI  - Stress among nurses working in an acute hospital in Ireland.
AB  - Stress among nurses leads to absenteeism, reduced efficiency, long-term health
      problems and a decrease in the quality of patient care delivered. A quantitative
      cross-sectional study was conducted. The study's aim was to identify perceived
      stressors and influencing factors among nurses working in the critical and non
      critical care practice areas. A convenience sample of 200 nurses were invited to
      complete the Bianchi Stress Questionnaire. Information was collected on
      demographics and daily nursing practice. Findings indicated that perceived
      stressors were similar in both groups. The most severe stressors included
      redeployment to work in other areas and staffing levels. Results from this study
      suggest that age, job title, professional experience and formal post-registration
      qualifications had no influence on stress perception. These results will increase
      awareness of nurses' occupational stress in Ireland. 

PMID- 25072340
TI  - Tackling the burden of dementia care in society.

PMID- 25072324
TI  - Cerebrospinal fluid markers including trefoil factor 3 are associated with
      neurodegeneration in amyloid-positive individuals.
AB  - We aimed to identify cerebrospinal fluid (CSF) biomarkers associated with
      neurodegeneration in individuals with and without CSF evidence of Alzheimer
      pathology. We investigated 287 Alzheimer's Disease Neuroimaging Initiative (ADNI)
      subjects (age=74.9+/-6.9; 22/48/30% with Alzheimer's disease/mild cognitive
      impairment/controls) with CSF multiplex analyte data and serial volumetric MRI.
      We calculated brain and hippocampal atrophy rates, ventricular expansion and Mini
      Mental State Examination decline. We used false discovery rate corrected
      regression analyses to assess associations between CSF variables and atrophy
      rates in individuals with and without amyloid pathology, adjusting in stages for
      tau, baseline volume, p-tau, age, sex, ApoE4 status and diagnosis. Analytes
      showing statistically significant independent relationships were entered into
      reverse stepwise analyses. Adjusting for tau, baseline volume, p-tau, age, sex
      and ApoE4, 4/83 analytes were significantly independently associated with brain
      atrophy rate, 1/83 with ventricular expansion and 2/83 with hippocampal atrophy.
      The strongest CSF predictor for the three atrophy measures was low trefoil factor
      3 (TFF3). High cystatin C (CysC) was associated with higher whole brain atrophy
      and hippocampal atrophy rates. Lower levels of vascular endothelial growth factor
      and chromogranin A (CrA) were associated with higher whole brain atrophy. In
      exploratory reverse stepwise analyses, lower TFF3 was associated with higher
      rates of whole brain, hippocampal atrophy and ventricular expansion. Lower levels
      of CrA were associated with higher whole brain atrophy rate. The relationship
      between low TFF3 and increased hippocampal atrophy rate remained after adjustment
      for diagnosis. We identified a series of CSF markers that are independently
      associated with rate of neurodegeneration in amyloid-positive individuals. TFF3,
      a substrate for NOTCH processing may be an important biomarker of
      neurodegeneration across the Alzheimer spectrum. 

PMID- 25072341
TI  - Good communication and the safe healthcare environment.

PMID- 25072342
TI  - Reflection: from staff nurse to nurse consultant. Part 11: reflection in life.

PMID- 25072343
TI  - Supporting students with disabilities: good progress, but must try harder.

PMID- 25072344
TI  - Co-production and quality outcomes.

PMID- 25072345
TI  - Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs
      in recipient cells.
AB  - MicroRNAs (miRNAs) secreted by cells into microvesicles (MVs) form a novel class
      of signal molecules that mediate intercellular communication. However, several
      fundamental aspects of secreted miRNAs remain unknown, particularly the mechanism
      that governs the function or fate of exogenous miRNAs in recipient cells. In the
      present study, we provide evidence indicating that Argonaute 2 (Ago2) plays a
      role in stabilizing miRNAs and facilitating the packaging of secreted miRNAs into
      MVs. More importantly, Ago2 in origin cell-secreted MVs (but not in recipient
      cells) directs the function of secreted miRNAs. First, Ago2 overexpression
      clearly increased the level of miR-16 in cells transfected with a miR-16 mimic by
      protecting the miRNAs from degradation in lysosomes. Second, Ago2 overexpression
      increased the level of miR-16 in cell-secreted MVs, suggesting that Ago2 may
      facilitate the packaging of secreted miRNAs into MVs. Third, exogenous miR-16
      delivered by MVs within the origin cells significantly reduced the Bcl2 protein
      level in recipient cells, and miR-16 and Bcl2 mRNA were physically associated
      with exogenous HA-tagged Ago2 (HA-Ago2). Finally, the effect of MV-delivered miR
      16 on the production of the Bcl2 protein in recipient cells was not abolished by
      knocking down Ago2 in the recipient cells. 

PMID- 25072346
TI  - A selective ultrahigh responding high temperature ethanol sensor using TiO2
      nanoparticles.
AB  - In this research work, the sensitivity of TiO2 nanoparticles towards C2H5OH, H2
      and CH4 gases was investigated. The morphology and phase content of the particles
      was preserved during sensing tests by prior heat treatment of the samples at
      temperatures as high as 750  degrees C and 1000  degrees C. Field emission
      scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and
      X-ray diffraction (XRD) analysis were employed to characterize the size,
      morphology and phase content of the particles. For sensor fabrication, a film of
      TiO2 was printed on a Au interdigitated alumina substrate. The sensing
      temperature was varied from 450  degrees C to 650  degrees C with varying
      concentrations of target gases. Results show that the sensor has ultrahigh
      response towards ethanol (C2H5OH) compared to hydrogen (H2) and methane (CH4).
      The optimum sensing temperature was found to be 600  degrees C. The response and
      recovery times of the sensor are 3 min and 15 min, respectively, for 20 ppm
      C2H5OH at the optimum operating temperature of 600  degrees C. It is proposed
      that the catalytic action of TiO2 with C2H5OH is the reason for the ultrahigh
      response of the sensor. 

PMID- 25072347
TI  - Humidity sensors printed on recycled paper and cardboard.
AB  - Research, design, fabrication and results of various screen printed capacitive
      humidity sensors is presented in this paper. Two types of capacitive humidity
      sensors have been designed and fabricated via screen printing on recycled paper
      and cardboard, obtained from the regional paper and cardboard industry. As
      printing ink, commercially available silver nanoparticle-based conductive ink was
      used. A considerable amount of work has been devoted to the humidity measurement
      methods using paper as a dielectric material. Performances of different
      structures have been tested in a humidity chamber. Relative humidity in the
      chamber was varied in the range of 35%-80% relative humidity (RH) at a constant
      temperature of 23  degrees C. Parameters of interest were capacitance and
      conductance of each sensor material, as well as long term behaviour. Process
      reversibility has also been considered. The results obtained show a mainly
      logarithmic response of the paper sensors, with the only exception being
      cardboard-based sensors. Recycled paper-based sensors exhibit a change in value
      of three orders of magnitude, whereas cardboard-based sensors have a change in
      value of few 10s over the entire scope of relative humidity range (RH 35%-90%).
      Two different types of capacitor sensors have been investigated: lateral (comb)
      type sensors and modified, perforated flat plate type sensors. The objective of
      the present work was to identify the most important factors affecting the
      material performances with humidity, and to contribute to the development of a
      sensor system supported with a Radio Frequency Identification (RFID) chip
      directly on the material, for use in smart packaging applications. Therefore, the
      authors built a passive and a battery-supported wireless module based on SL900A
      smart sensory tag's IC to achieve UHF-RFID functionality with data logging
      capability. 

PMID- 25072348
TI  - Smart elasto-magneto-electric (EME) sensors for stress monitoring of steel
      cables: design theory and experimental validation.
AB  - An elasto-magnetic (EM) and magneto-electric (ME) effect based elasto-magneto
      electric (EME) sensor has been proposed recently by the authors for stress
      monitoring of steel cables with obvious superiorities over traditional elasto
      magnetic sensors. For design optimization and engineering application of the EME
      sensor, the design theory is interpreted with a developed model taking into
      account the EM coupling effect and ME coupling effect. This model is able to
      approximate the magnetization changes that a steel structural component undergoes
      when subjected to excitation magnetic field and external stress, and to simulate
      the induced ME voltages of the ME sensing unit located in the magnetization area.
      A full-scale experiment is then carried out to verify the model and to calibrate
      the EME sensor as a non-destructive evaluation (NDE) tool to monitor the cable
      stress. The experimental results agree well with the simulation results using the
      developed model. The proposed EME sensor proves to be feasible for stress
      monitoring of steel cables with high sensitivity, fast response, and ease of
      installation. 

PMID- 25072350
TI  - Postoperative infection rates in patients with a negative baseline urine culture
      undergoing ureteroscopic stone removal: a matched case-control analysis on
      antibiotic prophylaxis from the CROES URS global study.
AB  - PURPOSE: To examine the effects of antibiotic prophylaxis on postoperative
      infection rate in patients with negative urine cultures undergoing ureteroscopy
      (URS). PATIENTS AND METHODS: Using the Clinical Research Office of the
      Endourological Society (CROES) URS Global Study database, patients with a
      negative baseline urine culture undergoing URS for ureteral stones (n=1141) or
      kidney stones (n=184) not receiving antibiotic prophylaxis were matched with
      those who were predefined by risk factors, including gender, American Society of
      Anesthesiologists (ASA) score, and ureteral stent placement. Patient
      characteristics, operative data, and postoperative outcomes, including the
      development of urinary tract infection (UTI) and fever, in the two groups were
      compared. RESULTS: Antibiotic prophylaxis use differed widely across
      participating countries (13%-100%). Differences were found between patients who
      did or did not receive antibiotic prophylaxis regarding the frequency of
      anticoagulation medication, previous treatment with URS, stone burden, previous
      presence of kidney stones, duration of current URS, and complications post-URS.
      The prevalence of fever and UTI was low (<=2.2%) and similar in both groups.
      Factors predictive of postoperative UTI or fever were female gender, Crohn's and
      cardiovascular disease, a high stone burden, and an ASA score of II or higher.
      CONCLUSIONS: In patients with a negative baseline urine culture undergoing URS
      for ureteral or renal stones, rates of postoperative UTI and fever were not
      reduced by preoperative antibiotic prophylaxis. Female gender and a high ASA
      score were specific risk factors for postoperative infection in this patient
      group.

PMID- 25072352
TI  - Prolonged fasting/refeeding promotes hematopoietic stem cell regeneration and
      rejuvenation.
AB  - The sensitivity of hematopoietic stem cells (HSCs) to toxic effects of cancer
      chemotherapy is one of the major roadblocks in cancer therapy. Moreover, the loss
      of HSC function in the elderly ("immunosenescence") is a major source of
      morbidity and mortality. Until recently, it was believed that HSCs were
      irreversibly damaged by the aging process. Recent work in mice shows that cycles
      of prolonged fasting (PF) of greater than 72 hr followed by refeeding can protect
      HSCs from the toxicity associated with chemotherapy and stimulate the
      proliferation of and rejuvenate old HSCs. A preliminary phase I trial in humans
      suggests that PF may confer benefit to people undergoing chemotherapy. These
      effects are at least partially mediated by lowered insulin-like growth factor-1
      levels in the blood and stem cell microenvironment, which leads to lowered
      protein kinase A (PKA) activity. Reducing PKA levels or activity can replicate at
      least some of the effects of PF on HSCs. Shorter periods of fasting were not
      effective. PF represents a potentially profound, low-tech means to enhance cancer
      treatment and reverse aging of the immune system in the elderly. Because PF is
      likely to be stressful to the old and fragile, the development of PF mimetics may
      be warranted.

PMID- 25072353
TI  - Transport in ferrocene single molecules for terahertz applications.
AB  - The transport properties of single ferrocene molecules connected to nanoscopic
      gold electrodes are investigated in the framework of density functional theory
      (DFT) calculations using the non-equilibrium Green's function formalism. Our
      setup describes a molecular rotor, where one cyclopentadienyl (Cp) ring of the
      ferrocene molecule is fixed by the two electrodes, while the second ring is able
      to rotate. For small enough rotation energies the barrier between the eclipsed
      and staggered conformations of the ferrocene molecule ensures the functionality
      of a molecular oscillator. The changes in the transmission function introduced by
      the relative rotation angle between the two Cp rings are analyzed in both linear
      and non-linear bias regimes. For larger rotation energies, the device works in
      the spinning mode. The real time behavior of the nanomechanical device is
      investigated using DFT-based molecular dynamics, which shows its feasibility for
      applications in the terahertz regime. In the oscillating mode the natural
      frequencies are determined, while the spinning mode shows a remarkably reliable
      behavior with increasing rotation energy. 

PMID- 25072354
TI  - Hypotensive and antihypertensive potential of 4-[(1-phenyl-1H-pyrazol-4-yl)
      methyl]1-piperazine carboxylic acid ethyl ester: a piperazine derivative.
AB  - AIMS: Clinical complaints on the first-line of cardiovascular medications make
      continuous search for new drugs a necessity. This study evaluated the
      cardiovascular effects and mechanism of 4-[(1-phenyl-1H-pyrazol-4-yl)methyl]1
      piperazine carboxylic acid ethyl ester (LQFM008). MAIN METHODS: Normotensive male
      Wistar or spontaneously hypertensive rats (anesthetized or conscious) were used
      to evaluate the effect of LQFM008 on the mean arterial pressure (MAP), heart rate
      (HR), arterial blood flow (ABF), arterial vascular conductance (AVC), baroreflex
      effectiveness index (BI), systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and vascular function. KEY FINDINGS: In anesthetized normotensive rats,
      LQFM008 (7.3, 14.3 or 28.6 MUmol/kg, i.v.) reduced MAP (-21.1+/-2.7; -23.9+/-4.7
      or -32.4+/-8.3 mmHg, respectively) and AVC (22%, 32% or 38%) in a dose-dependent
      manner. LQFM008 elicited a temporal reduction in the SBP and DBP without changes
      to the BI of conscious normotensive rats. In hypertensive rats, LQFM008 (7.3,
      14.3 or 28.6 MUmol/kg, i.v.) reduced MAP (-2.3+/-2.6; -29.3+/-2.7 or -38.4+/-2.8
      mmHg, respectively) and increased HR (1.6+/-3.7; 15.4+/-4.9 or 25.5+/-6.2 bmp,
      respectively) in a dose-dependent manner. A week of oral administration of
      LQFM008 47.7 MUmol/kg elicited a temporal reduction in SBP of hypertensive rats.
      Pretreatments with atropine, WAY-100635 or L-NAME blocked the effect of LQFM008.
      In addition, LQFM008-induced endothelium-dependent vascular relaxation was
      inhibited by L-NAME. SIGNIFICANCE: Our findings showed hypotensive,
      antihypertensive and vasorelaxant effects of LQFM008 and suggest the
      participation of nitric oxide, 5-HT1A and muscarinic receptors.

PMID- 25072355
TI  - Beneficial effect of Calculus Bovis Sativus on 17alpha-ethynylestradiol-induced
      cholestasis in the rat.
AB  - AIMS: Calculus Bovis Sativus (CBS) shares similar pharmacological effects with
      Calculus Bovis like relieving hepatobiliary diseases. This study aims to
      investigate the effect and mechanism of CBS on 17alpha-ethynylestradiol (EE)
      induced cholestasis in the rat. MAIN METHODS: CBS (50 and 150 mg/kg per day) was
      intragastrically (i. g.) given to experimental rats for 5 consecutive days in
      coadministration with EE. The levels of serum biomarkers, hepatic malondialdehyde
      (MDA) content and superoxide dismutase (SOD) activity were determined by
      biochemical methods. The bile flow in 2h was measured. The histopathology of the
      liver tissue was evaluated. The expression of transporter was studied by reverse
      transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and
      western blot. KEY FINDINGS: CBS treatment significantly prevented EE-induced
      increases in serum levels of biomarkers. Decreased bile flow by EE was restored
      with CBS treatment. The tissue lesions were also relieved with CBS treatment.
      Western blot studies indicated that EE significantly decreased the protein
      expression of multidrug resistance-associated protein 2 (Mrp2) and breast cancer
      resistance protein (Bcrp), but notably increased P-glycoprotein (P-gp) protein,
      compared with the control group. CBS treatment significantly increased the
      protein expression of P-gp, Mrp2 and Bcrp compared with the EE group. RT-qPCR
      studies indicated that EE down-regulated Bcrp at transcriptional level. CBS up
      regulated the mRNA expression of P-gp, Mrp2 and Bcrp compared with the EE group.
      SIGNIFICANCE: The present study indicated that CBS exerted a beneficial effect on
      EE-induced cholestasis in the rat, which may result from its induction of P-gp,
      Mrp2 and Bcrp expression.

PMID- 25072356
TI  - H2S preconditioning of human adipose tissue-derived stem cells increases their
      efficacy in an in vitro model of cell therapy for simulated ischemia.
AB  - AIMS: A major limitation of cell-based therapies for ischemia-reperfusion injury
      is the excessive loss of administered cells. We investigated whether H2S can
      improve the survival and efficacy of therapeutic cells in an in vitro model of
      cell-based therapy for simulated ischemia. MAIN METHODS: H9c2 rat cardiomyoblasts
      were exposed to oxygen-glucose deprivation and NaHS (3-30 MUM) pretreated human
      adipose tissue derived stem cells (hASCs) were added after reoxygenization.
      Viability of both cell lines was assessed with flow cytometry after 24h. The
      effects of H2S on antioxidant defense, proliferation, AKT and ERK1/2
      phosphorylation and mitochondrial activity were analyzed in hASCs. Proliferation
      was evaluated using propargylglycine, an inhibitor of endogenous H2S synthesis.
      KEY FINDINGS: NaHS pretreatment decreased the ratio of necrotic therapeutic cells
      by 41.8% in case of 3 MUM NaHS and by 34.3% with 30 MUM NaHS. The ratio of
      necrotic postischemic cardiomyocytes decreased by 35%, but only with the use of 3
      MUM NaHS. Antioxidant defense mechanisms and ERK-phosphorylation were enhanced
      after 3 MUM NaHS treatment while AKT-phosphorylation was suppressed. NaHS dose
      dependently increased the proliferation of hASCs while pretreatment with
      propargylglycine decreased it. SIGNIFICANCE: NaHS pretreatment can increase the
      survival of therapeutically used human adipose tissue-derived stem cells via
      increased antioxidant defense and improves the postischemic cardiac derived
      cells' survival as well. Proliferation of human adipose tissue-derived stem cells
      is enhanced by H2S. The underlying mechanisms involve enhanced ERK
      phosphorylation and decreased AKT-phosphorylation. Pretreatment with NaHS may
      represent a simple pharmacological step that may enhance the efficacy of cell
      based therapies.

PMID- 25072358
TI  - Transition-state searches in metal clusters by first-principle methods.
AB  - Elucidation of the chemical reactivity of metal clusters is often cumbersome due
      to the nonintuitive structures of the corresponding transition states. In this
      work, a hierarchical transition-state algorithm as implemented in the deMon2k
      code has been applied to locate transition states of small sodium clusters with 6
      10 atoms. This algorithm combines the so-called double-ended interpolation method
      with the uphill trust region method. The minimum structures needed as input were
      obtained from Born-Oppenheimer molecular dynamics simulations. To connect the
      found transition states with the corresponding minimum structures, the intrinsic
      reaction coordinates were calculated. This work demonstrates how nonintuitive
      rearrangement mechanisms can be studied in metal clusters. 

PMID- 25072357
TI  - Attenuation of IFN-gamma-induced B7-H1 expression by 15-deoxy-delta(12,14)
      prostaglandin J2 via downregulation of the Jak/STAT/IRF-1 signaling pathway.
AB  - AIM: B7-H1, which belongs to the B7 family of costimulatory molecules, is
      implicated in the ability of tumors to evade the host immune response. The
      development of evasion mechanisms within the tumor microenvironment may be
      responsible for poor therapeutic responses. In this manuscript, we report that
      the 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), peroxisome proliferator
      activated receptor gamma (PPARgamma) activator leads to the downregulation of the
      cancer-associated expression of B7-H1 in response to interferon-gamma (IFN-gamma)
      and the associated signaling cascades. MAIN METHODS: The expression of B7-H1 from
      IFN-gamma-induced B16F10 melanoma cells was measured with flow cytometric
      analysis. The regulatory mechanisms of 15d-PGJ2 on cellular signaling pathways
      were examined using Western blot and electrophoretic mobility shift assays. KEY
      FINDINGS: The flow cytometric analysis revealed that the B7-H1 costimulatory
      molecule is significantly upregulated in B16F10 melanoma cells by stimulation
      with IFN-gamma. However, 15d-PGJ2 strongly downregulates B7-H1 expression in IFN
      gamma-stimulated B16F10 melanoma cells. Furthermore, the significant damping
      effect of 15d-PGJ2 on B7-H1 expression involves the inhibition of the tyrosine
      phosphorylation of Janus kinase (Jak) and signal transducer(s) and activator(s)
      of transcription (STAT) and, thereby, the interferon regulatory factor-1 (IRF-1)
      trans-activation of STAT. These effects of 15d-PGJ2 were not abrogated by the
      PPARgamma antagonist GW9662, indicating that they occur through a PPARgamma
      independent mechanism. SIGNIFICANCE: In this study, we demonstrate that 15d-PGJ2
      suppresses the IFN-gamma-elicited expression of B7-H1 by the inhibition of IRF-1
      transcription via the Jak/STAT signaling pathway through a PPARgamma-independent
      mechanism in mouse melanoma cells.

PMID- 25072359
TI  - Screening and identification of potential biomarkers and establishment of the
      diagnostic serum proteomic model for the Traditional Chinese Medicine Syndromes
      of tuberculosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chemotherapy is the mainstay of modern
      tuberculosis (TB) control. Traditional Chinese Medicine (TCM) can enhance the
      effect of anti-TB drug, promote the absorption of the foci in the lung and reduce
      drug toxicity. In TCM, the determination of treatment is based on ZHENG (also
      called TCM syndrome). To establish a diagnostic model by using proteomics
      technology in order to identify potential biomarkers for TCM syndromes of TB.
      MATERIALS AND METHODS: The surface-enhanced laser desorption ionization time of
      flight mass spectrometer (SELDI-TOF MS) combined with weak cation exchange (WCX)
      magnetic beads was used to screen serum samples from 71 cases of deficiency of
      lung yin syndrome (DLYS), 64 cases of fire (yang) excess yin deficiency syndrome
      (FEYDS) and 45 cases of deficiency of both qi and yin syndrome (DQYS). A
      classification model was established by Biomarker Pattern Software (BPS).
      Candidate protein biomarkers were purified by reverse phase-high performance
      liquid chromatograph (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and
      validated by ProteinChip Immunoassays. RESULTS: A total of 74 discriminating m/z
      peaks (P<0.001) among three TCM syndromes of TB were detected. A diagnostic model
      for the TCM syndrome of TB based on the five biomarkers (3961.7, 4679.7, 5646.4,
      8891.2 and 9416.7 m/z) was established which could discriminate DLYS, FEYDS and
      DQYS patients with an accuracy of 74.0%, 72.5%, and 96.7%, respectively. The
      candidate biomarker with m/z of 9416.7 was identified as a fragment of
      apolipoprotein C-III (apoC-III) by MALDI-TOF-MS and LC-MS/MS. CONCLUSION: The TCM
      syndrome diagnostic model of TB could successfully distinguish the three TCM
      syndromes of TB patients. This provided a biological basis for the determination
      of treatment based on different TCM syndromes of TB. ApoC-III was identified as a
      potential biomarker for TCM syndromes of TB and revealed the biochemical basis
      and pathogenesis of TCM syndromes in TB.

PMID- 25072360
TI  - An ethnopharmacological assessment of the use of plants against parasitic
      diseases in humans and animals.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical surveys are detecting an
      increasing frequency of exotic plant species in pharmacopeias, which has led
      researchers to investigate the role of such species in traditional medical
      systems. According to the diversification hypothesis, exotic species are included
      to complete pharmacopeias, i.e., to treat diseases for which no native species
      are known, thus broadening the scope of the plant repertoire. MATERIALS AND
      METHODS: The present study was conducted at two rural communities in northeastern
      Brazil aiming at a survey of the plants known or used by the population to treat
      endo- and ectoparasitic diseases in humans and animals. In addition, plant
      extracts exhibiting acaricide activity were assessed using the engorged female
      immersion and larval packet tests (LPT). RESULTS: The results of the present
      study showed a tendency for native species to be used against ectoparasites and
      exhibit a broader scope of use compared to exotic species. In turn, exotic
      species were predominantly indicated to treat diseases caused by endoparasites,
      although there was an overlap of native and exotic species relative to some
      therapeutic purpose, e.g., ticks. Only two of the plant species tested exhibited
      acaricide activity (Nicotiana glauca Graham and Croton blanchetianus Baill.), and
      in both cases, the activity was weak. CONCLUSION: The ethnobotanical data do not
      fully support the suggested hypothesis. Overall, the wide versatility of exotic
      species was not exclusively used to treat parasitic diseases in humans and
      animals. In addition, the selection of acaricide plants based on the
      ethnopharmacological study generated uninteresting results.

PMID- 25072361
TI  - Ginseng treatment reverses obesity and related disorders by inhibiting
      angiogenesis in female db/db mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng (ginseng, Panax ginseng C.A.
      Meyer) has traditionally been used in the treatment of most ageing-related
      diseases, such as obesity, diabetes, and dyslipidemia, but the mechanism of the
      effects is unclear. The aim of this study was to determine the effects of ginseng
      on obesity in a mouse model of female obesity (obese female db/db mouse) and to
      investigate the mechanism of anti-obesity effects. MATERIALS AND METHODS: After
      female db/db (B6.Cg-m Lepr(db)/++/J) mice were treated with 5% (w/w) ginseng for
      13 weeks, variables and parameters of obesity and disorders related to obesity
      were examined. Blood vessel density and the expression of genes involved in
      angiogenesis were also measured. RESULTS: Mice treated with ginseng for 13 weeks
      had less body weight and lower adipose tissue mass compared to control, untreated
      mice. The size of adipocytes was smaller in visceral adipose tissues of ginseng
      treated mice. Obesity-related complications, such as hepatic steatosis,
      hypertriglyceridemia, and hyperglycemia, were markedly improved in treated mice.
      Blood vessel density was lower in visceral adipose tissue sections from treated
      mice than those from control mice. Concomitantly, mRNA levels for VEGF-A and FGF
      2 were lower in both visceral adipose tissue from treated mice and treated 3T3-L1
      cells compared to those from untreated controls. Protein levels for VEGF were
      also lower in visceral adipose tissue from treated mice. In contrast, ginseng
      increased mRNA expression of genes responsible for energy expenditure and fatty
      acid beta-oxidation in visceral adipose tissue during ginseng-induced weight
      reduction. CONCLUSIONS: These results suggest that ginseng may effectively treat
      female obesity and related disorders in part by inhibition of angiogenesis.

PMID- 25072362
TI  - Effectiveness of non-conventional methods for accelerated orthodontic tooth
      movement: a systematic review and meta-analysis.
AB  - OBJECTIVES: To assess the available evidence on the effectiveness of accelerated
      orthodontic tooth movement through surgical and non-surgical approaches in
      orthodontic patients. METHODS: Randomized controlled trials and controlled
      clinical trials were identified through electronic and hand searches (last
      update: March 2014). Orthognathic surgery, distraction osteogenesis, and
      pharmacological approaches were excluded. Risk of bias was assessed using the
      Cochrane risk of bias tool. RESULTS: Eighteen trials involving 354 participants
      were included for qualitative and quantitative synthesis. Eight trials reported
      on low-intensity laser, one on photobiomodulation, one on pulsed electromagnetic
      fields, seven on corticotomy, and one on interseptal bone reduction. Two studies
      on corticotomy and two on low-intensity laser, which had low or unclear risk of
      bias, were mathematically combined using the random effects model. Higher canine
      retraction rate was evident with corticotomy during the first month of therapy
      (WMD=0.73; 95% CI: 0.28, 1.19, p<0.01) and with low-intensity laser
      (WMD=0.42mm/month; 95% CI: 0.26, 0.57, p<0.001) in a period longer than 3 months.
      The quality of evidence supporting the interventions is moderate for laser
      therapy and low for corticotomy intervention. CONCLUSIONS: There is some evidence
      that low laser therapy and corticotomy are effective, whereas the evidence is
      weak for interseptal bone reduction and very weak for photobiomodulation and
      pulsed electromagnetic fields. Overall, the results should be interpreted with
      caution given the small number, quality, and heterogeneity of the included
      studies. Further research is required in this field with additional attention to
      application protocols, adverse effects, and cost-benefit analysis. CLINICAL
      SIGNIFICANCE: From the qualitative and quantitative synthesis of the studies, it
      could be concluded that there is some evidence that low laser therapy and
      corticotomy are associated with accelerated orthodontic tooth movement, while
      further investigation is required before routine application.

PMID- 25072363
TI  - Pharmacokinetic and safety profiles of repeated-dose prophylactic micafungin in
      children and adolescents undergoing hematopoietic stem cell transplantation.
AB  - Micafungin is a potent echinocandin antifungal that can be used for both
      prophylaxis and treatment of Candida infections. This open-label study assessed
      the pharmacokinetics and safety profile of prophylactic micafungin in children
      and adolescents (aged 4 mo to 16 y) undergoing hematopoietic stem cell
      transplantation. Patients received once-daily doses of either 1 or 1.5 mg/kg
      micafungin, based on their body weight, for 10 to 14 days. In total, 40 patients
      received micafungin. Area under the plasma micafungin concentration-time curve
      was highest in patients aged 6 to 11 years in the 1.5 mg/kg treatment group. Peak
      plasma micafungin concentration displayed no age-related differences, but was
      higher in the 1.5 mg/kg versus the 1 mg/kg group. Clearance at steady state by
      weight and volume of distribution by weight were considerably higher in patients
      aged 4 months to 5 years. Results from this study show that age and body weight
      affect micafungin pharmacokinetics in pediatric patients undergoing hematopoietic
      stem cell transplantation.

PMID- 25072364
TI  - Chemotherapy-induced alteration of SDF-1/CXCR4 expression in bone marrow-derived
      mesenchymal stem cells from adolescents and young adults with acute lymphoblastic
      leukemia.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs) in the marrow stroma provide
      a scaffold for hematopoiesis. Chemokine stromal cell-derived factor-1 (SDF-1) and
      its receptor CXCR4 have been shown to affect the engraftment of hematopoietic
      stem cells. However, little is known about SDF-1/CXCR4's functions in regulating
      BM-MSCs in humans. As an initial step toward this issue, we have evaluated
      expression of SDF-1/CXCR4 in the BM-MSCs from a cohort of adolescents and young
      adults with acute lymphoblastic leukemia (ALL). We found a decrease of the CXCR4
      level and an increase of the SDF-1 level in these MSCs of ALL. Moreover, cell
      migration appeared to be impaired in the MSCs of ALL. These changes were reversed
      by chemotherapy. Taken together, alteration of SDF-1/CXCR4 expression could be
      potentially developed as biomarkers for monitoring the effectiveness of
      chemotherapy. 

PMID- 25072365
TI  - Successful hematopoietic reconstitution by unrelated donor cord blood
      transplantation in children with Fanconi anemia: report of 3 cases.
AB  - To potentially reduce late effects of malignancy and chronic graft-versus-host
      disease in patients with Fanconi anemia, 3 patients received unmanipulated
      umbilical cord blood grafts with 0 or 1 HLA antigen mismatch. The conditioning
      regimen consisted of fludarabine (30 mg/m/d) for 6 days, cyclophosphamide (60
      mg/kg/d) for 2 days, and rabbit antithymocyte globulin (ATG) (2.5 mg/kg/d) for 3
      days. Radiation was not used in the preparative regimen. None of the patients had
      significant conditioning-related toxicity. All were engrafted within 10 to 19
      days. All patients are well with stable or full donor chimerism after a median
      follow-up of 64 months (range, 13 to 69 mo). 

PMID- 25072366
TI  - Hydroa vacciniforme-like lymphoma: a case report from India.
AB  - We report a 14-year-old Indian boy who presented with a history of weight loss,
      fever, facial edema, and a relapsing papulovesicular eruption on the face and
      limbs for 1 year. Histopathology of the skin showed dense lymphoid infiltrate
      from dermis to subcutaneous fat. Immunohistochemistry of this lymphoid infiltrate
      was CD3, CD8, CD56, CD57, Granzyme B, TIA, and Epstein Barr virus LMP1. The
      histopathology and immunohistochemistry were consistent with the diagnosis of
      hydroa vacciniforme-like T-cell lymphoma. The child responded remarkably to oral
      steroids but relapsed on tapering doses. CHOP (Cyclophosphamide, Adriamycin,
      Vincristine, and Prednisolone) chemotherapy was initiated in view of systemic
      involvement to which he showed some response, however, the disease relapsed
      again. He then had a rapidly progressive disease and ultimately succumbed to his
      illness. This is the first case of hydroa vacciniforme-like T-cell lymphoma being
      reported from this subcontinent. 

PMID- 25072367
TI  - Understanding and improving health education among first-time parents of infants
      with sickle cell anemia in Alabama: a mixed methods approach.
AB  - With the increase in access to medical information, parents can acquire health
      information from multiple sources. An understanding of parents' reactions to a
      newborn infant's diagnosis of sickle cell anemia and how they acquire knowledge
      can identify parent beliefs and preferences about the process of sickle cell
      education. This study utilized a sequential exploratory mixed methods design.
      First, qualitative interviews were conducted with 8 parents of infants with
      sickle cell anemia to understand the process of health education. Second,
      quantitative surveys were conducted with 22 other parents to test qualitative
      findings. Parents of infants with sickle cell anemia expressed a high level of
      fear at the time of notification of a positive screen. Parents desired an
      understanding of how to identify acute complications of disease and how sickle
      cell will alter their child's life. Parents actively sought information at the
      time they were told their child had sickle cell disease. Sickle cell education
      should begin at time of notification of positive newborn screening results and
      address identified parent concerns. Health care providers should build trust with
      parents and provide them with immediate access to educational materials.
      Hematologists should work with primary care providers to develop complementary
      educational programs and resources.

PMID- 25072368
TI  - Clinical Trial Decision Making in Pediatric Sickle Cell Disease: A Qualitative
      Study of Perceived Benefits and Barriers to Participation.
AB  - Clinical trial research forms the foundation for advancing treatments; yet,
      children with sickle cell disease (SCD) are currently underrepresented. This
      qualitative study examines decision-making processes of youth with SCD and their
      caregivers regarding enrollment in clinical trial research. A subsample of
      participants from a study of clinical trial decision making among youth with
      health disparity conditions, 23 caregivers and 29 children/teens/young adults
      with SCD (age, 10 to 29 y), indicated whether or not they would participate in
      hypothetical medical and psychosocial clinical trials and prioritized barriers
      and benefits to participation via card sort and semistructured interviews. Audio
      recordings were transcribed and coded for themes. Participants reported that
      concerns of potential harm most affected their decision. Secondary factors were
      potential benefit, manageable study demands, and trust in the medical staff.
      Caregivers weighed potential harm more heavily than their children. Young
      children were more likely to endorse potential benefit. Overall, participants
      stated they would be willing to participate in research if the potential benefit
      outweighs potential harm and unmanageable study demands. To optimize recruitment,
      results suggest addressing potential harm first while highlighting potential
      benefits, creating manageable study demands, and endorsing the future benefits of
      research to the sickle cell community. 

PMID- 25072369
TI  - Leukocyte adhesion deficiency type III: clinical features and treatment with stem
      cell transplantation.
AB  - Leukocyte adhesion deficiency type III (LADIII) is an autosomal recessive
      disorder that presents with a severe leukocyte adhesion defect and a Glanzmann
      type thrombocytopathy. Hematopoietic stem cell transplantation (HSCT)--the only
      definitive treatment for LADIII--appears to have a high rate of complications. In
      this study, we describe a new group of patients with LADIII, highlighting further
      clinical and immunologic aspects of this disease, and reevaluating the
      effectiveness of HSCT for its treatment. The patients had clinical and laboratory
      findings consistent with LADIII. Molecular analysis confirmed the presence of a
      mutation in the kindlin-3 gene. HSCT was carried out in 3 patients and was
      successful in 2. The diagnosis of LADIII should be considered in all patients who
      present with recurrent infections and a bleeding diathesis, regardless of the
      leukocyte count. LADIII is a primary immune deficiency, which can be successfully
      corrected by bone marrow transplantation if applied early in the course of the
      disease using appropriate conditioning.

PMID- 25072370
TI  - Coinfusion of mobilized hematopoietic stem cells from an HLA-mismatched third
      party donor with umbilical cord blood graft to support engraftment.
AB  - We evaluated the role of mismatched third-party hematopoietic stem cells (TPC) in
      shortening the neutropenia after umbilical cord blood transplantation (UCBT). A
      TPC graft was given to 7/37 children with UCBT to support engraftment due to
      anticipated increased risk of nonengraftment (N=6) or active infection (N=1). TPC
      grafts were collected with apheresis from haploidentical family members. The
      median UCB and CD34 cell counts were 5.10 (range, 4.13 to 9.98)*10/kg and 5.98
      (range, 4.40 to 14.00)*10/kg, respectively. The median time to neutrophil
      engraftment was shorter in the patients with TPC (12 d; range, 9 to 24 d) than
      those without (23 d; range, 12 to 44 d) (P=0.010). TPC chimerism was lost in
      median at 28 (range, 24 to 103) days posttransplant. TPC grafts from mothers
      engrafted similarly as the grafts from other family members. UCB graft cell count
      and the use of methotrexate posttransplant strongly contributed to engraftment.
      TPC may form a valuable transient bridging graft over the neutropenia after UCBT
      in patients with anticipated high-risk of nonengraftment or toxicity due to
      pretransplant infections. 

PMID- 25072371
TI  - Hemiparesis in an Adolescent With Acute Lymphoblastic Leukemia: Everything Is Not
      Always What it Seems.
AB  - Acute lymphoblastic leukemia is a common malignancy in childhood. Managing
      adverse events during treatment can result in very complex situations. A
      previously healthy adolescent diagnosed with T-cell acute lymphoblastic leukemia
      developed on day +55 of induction chemotherapy hemiparesis, dysesthesia, and
      facial palsy. Blood tests and brain imaging techniques were unremarkable. The
      patient was diagnosed with a conversion disorder, which completely resolved.
      Although rare in clinical practice, children and adolescents with cancer do not
      always have organic pathology explaining their symptoms. Psychiatric disorders
      such as those of the somatoform spectrum must be considered, particularly in
      patients with anxiety or depression. 

PMID- 25072372
TI  - Invasive fungal infections in children with hematologic and malignant diseases.
AB  - BACKGROUND: To evaluate the clinical feature and outcome of invasive fungal
      infections (IFI) in children with hematologic and malign diseases. PATIENTS AND
      METHODS: The medical records of children with hematologic and malignant diseases,
      who were hospitalized at our hospital between January 2010 and December 2011,
      were reviewed. Proven, probable, and possible IFIs were diagnosed according to
      the revised definitions of the European Organization for Research and Treatment
      of Cancer/Mycosis Study Group. The demographic, clinical, and laboratory
      characteristics of the patients who met the study criteria were evaluated.
      RESULTS: IFI was diagnosed in 67 (7.2%) febrile episodes of 56 patients, of which
      10 (1.2%) were proven, 20 (2%) probable, and 37 (4%) possible IFI. Blood culture
      of 10 cases with proven IFI yielded yeast and the most common isolated agent was
      Candida parapsilosis. Seventy percent of cases with fungemia had central venous
      catheter (CVC). Twenty cases with probable IFI had invasive mold infection. The
      cases with mold infection had higher median C-reactive protein values, lower
      neutrophil counts, and longer duration of neutropenia compared with the cases
      with yeast infection. A total of 14 patients (20.9%) died. Presence of CVC, bone
      marrow transplantation, total parenteral nutrition, prolonged fever, and
      proven/probable IFI were detected more often in patients who died, compared with
      patients who survived. CONCLUSIONS: IFIs are important causes of death in
      children with hematologic and malignant diseases. Mold infections are seen more
      frequently in cases with prolonged and profound neutropenia, and invasive yeast
      infections, especially with non-albicans Candida species, in cases with CVC.
      Early and effective treatment considering these findings will help to decrease
      the mortality.

PMID- 25072373
TI  - Random search algorithm for solving the nonlinear Fredholm integral equations of
      the second kind.
AB  - In this paper, a randomized numerical approach is used to obtain approximate
      solutions for a class of nonlinear Fredholm integral equations of the second
      kind. The proposed approach contains two steps: at first, we define a discretized
      form of the integral equation by quadrature formula methods and solution of this
      discretized form converges to the exact solution of the integral equation by
      considering some conditions on the kernel of the integral equation. And then we
      convert the problem to an optimal control problem by introducing an artificial
      control function. Following that, in the next step, solution of the discretized
      form is approximated by a kind of Monte Carlo (MC) random search algorithm.
      Finally, some examples are given to show the efficiency of the proposed approach.

PMID- 25072374
TI  - Phytophthora *stagnum nothosp. nov., a new hybrid from irrigation reservoirs at
      ornamental plant nurseries in Virginia.
AB  - A novel Phytophthora species was frequently recovered from irrigation reservoirs
      at several ornamental plant production facilities in eastern Virginia. Initial
      sequencing of the internal transcribed spacer (ITS) region of this species
      generated unreadable sequences due to continual polymorphic positions. Cloning
      and sequencing the ITS region as well as sequencing the mitochondrially encoded
      cytochrome c oxidase 1 and beta-tubulin genes revealed that it is a hybrid
      between P. taxon PgChlamydo as its paternal parent and an unknown species
      genetically close to P. mississippiae as its maternal parent. This hybrid has
      some diagnostic morphological features of P. taxon PgChlamydo and P.
      mississippiae. It produces catenulate hyphal swellings, characteristic of P.
      mississippiae, and chlamydospores, typical of P. taxon PgChlamydo. It also
      produces both ornamented and relatively smooth-walled oogonia. Ornamented oogonia
      are another important diagnostic character of P. mississippiae. The relatively
      smooth-walled oogonia may be indicative of oogonial character of P. taxon
      PgChlamydo. The new hybrid is described here as Phytophthora *stagnum. 

PMID- 25072376
TI  - Fluorescence of dyes in solutions with high absorbance. Inner filter effect
      correction.
AB  - Fluorescence is a proven tool in all fields of knowledge, including biology and
      medicine. A significant obstacle in its use is the nonlinearity of the dependence
      of the fluorescence intensity on fluorophore concentration that is caused by the
      so-called primary inner filter effect. The existing methods for correcting the
      fluorescence intensity are hard to implement in practice; thus, it is generally
      considered best to use dilute solutions. We showed that correction must be
      performed always. Furthermore, high-concentration solutions (high absorbance) are
      inherent condition in studying of the photophysical properties of fluorescent
      dyes and the functionally significant interactions of biological macromolecules.
      We proposed an easy to use method to correct the experimentally recorded total
      fluorescence intensity and showed that informative component of fluorescence
      intensity numerically equals to the product of the absorbance and the
      fluorescence quantum yield of the object. It is shown that if dye molecules do
      not interact with each other and there is no reabsorption (as for NATA) and
      spectrofluorimeter provides the proportionality of the detected fluorescence
      intensity to the part of the absorbed light (that is possible for
      spectrofluorimeter with horizontal slits) then the dependence of experimentally
      detected total fluorescence intensity of the dye on its absorbance coincides with
      the calculated dependence and the correction factor for eliminating the primary
      inner filter effect can be calculated on the basis of solution absorbance. It was
      experimentally shown for NATA fluorescence in the wide range of absorbance (at
      least up to 60). For ATTO-425, which fluorescence and absorption spectra overlap,
      the elimination of the primary and secondary filter effects and additional
      spectral analysis allow to conclude that the most probable reason of the
      deviation of experimentally detected fluorescence intensity dependence on
      solution absorbance from the calculated dependence is the dye molecules self
      quenching, which accompanies resonance radiationless excitation energy transfer. 

PMID- 25072375
TI  - TGF-beta signaling initiated in dendritic cells instructs suppressive effects on
      Th17 differentiation at the site of neuroinflammation.
AB  - While the role of Transforming Growth Factor beta (TGF-beta) as an intrinsic
      pathway has been well established in driving de novo differentiation of Th17
      cells, no study has directly assessed the capacity of TGF-beta signaling
      initiated within dendritic cells (DCs) to regulate Th17 differentiation. The
      central finding of this study is the demonstration that Th17 cell fate during
      autoimmune inflammation is shaped by TGF-beta extrinsic pathway via DCs. First,
      we provide evidence that TGF-beta limits at the site of inflammation the
      differentiation of highly mature DCs as a means of restricting Th17 cell
      differentiation and controlling autoimmunity. Second, we demonstrate that TGF
      beta controls DC differentiation in the inflammatory site but not in the priming
      site. Third, we show that TGF-beta controls DC numbers at a precursor level but
      not at a mature stage. While it is undisputable that TGF-beta intrinsic pathway
      drives Th17 differentiation, our data provide the first evidence that TGF-beta
      can restrict Th17 differentiation via DC suppression but such a control occurs in
      the site of inflammation, not at the site of priming. Such a demarcation of the
      role of TGF-beta in DC lineage is unprecedented and holds serious implications
      vis-a-vis future DC-based therapeutic targets. 

PMID- 25072377
TI  - Towards the taxonomic categorization and recognition of nanoparticle shapes.
AB  - The shape of nanoparticles and nanomaterials is a fundamental characteristic that
      has been shown to influence a number of their properties and effects,
      particularly for nanomedical applications. The information related with this
      feature of nanoparticles and nanomaterials is, therefore, crucial to exploit and
      foster in existing and future research in this area. We have found that
      descriptions of morphological and spatial properties are consistently reported in
      the nanotechnology literature, and in general, these morphological properties can
      be observed and measured using various microscopy techniques. In this paper, we
      outline a taxonomy of nanoparticle shapes constructed according to
      nanotechnologists' descriptions and formal geometric concepts that can be used to
      address the problem of nanomaterial categorization. We employ an image
      segmentation technique, belonging to the mathematical morphology field, which is
      capable of identifying shapes in images that can be used to (semi-) automatically
      annotate nanoparticle images. FROM THE CLINICAL EDITOR: This team of authors
      outlines a taxonomy of nanoparticle shapes constructed according to
      nanotechnologists' descriptions and formal geometric concepts enabling
      nanomaterial categorization. They also employ a mathematical morphology-based
      image segmentation system, capable of identifying shapes and can be utilized in
      semi-automated annotation of nanoparticle images.

PMID- 25072378
TI  - Blood biocompatibility of surface-bound multi-walled carbon nanotubes.
AB  - Blood clots when it contacts foreign surfaces following platelet activation. This
      can be catastrophic in clinical settings involving extracorporeal circulation
      such as during heart-lung bypass where blood is circulated in polyvinyl chloride
      tubing. Studies have shown, however, that surface-bound carbon nanotubes may
      prevent platelet activation, the initiator of thrombosis. We studied the blood
      biocompatibility of polyvinyl chloride, surface-modified with multi-walled carbon
      nanotubes in vitro and in vivo. Our results show that surface-bound multi-walled
      carbon nanotubes cause platelet activation in vitro and devastating thrombosis in
      an in vivo animal model of extracorporeal circulation. The mechanism of the pro
      thrombotic effect likely involves direct multi-walled carbon nanotube-platelet
      interaction with Ca(2+)-dependant platelet activation. These experiments provide
      evidence, for the first time, that modification of surfaces with nanomaterials
      modulates blood biocompatibility in extracorporeal circulation.

PMID- 25072379
TI  - Detection of H3N2 canine influenza virus using a Quartz Crystal Microbalance.
AB  - Label-free technology-based Quartz Crystal Microbalance (QCM) is an emerging tool
      in biological research. In this study, QCM was applied successfully for the rapid
      diagnosis of H3N2 canine influenza virus (CIV) infection. ProLinkerTM B, a
      calixcrown derivative, enables antibodies to be attached to a gold-coated quartz
      surface and positioned in a regular pattern with the correct orientation. The
      ProLinker-coated quartz-based assay detected H3N2 CIV at lower concentrations
      (2(2) HA unit) than a commercial immunochromatography Ag kit (2(3) HA unit).
      Three independent experiments in which H3N2 CIV-positive reference samples were
      applied to an anti-CIV nucleoprotein (NP) monoclonal antibody immobilized on a
      quartz surface yielded standard deviations (SD) of <=5%, indicating high
      reproducibility. In addition, the QCM assay with a cut-off value (-140 Hz) showed
      97.1% (34/35) sensitivity and 94.7% (36/38) specificity in testing 73 field
      saliva samples, respectively. Thus, the QCM assay described herein will be a
      valuable tool for the rapid diagnosis of H3N2 CIV infection with high sensitivity
      and specificity, and should overcome several of the disadvantages and limitations
      inherent in the commercial immunochromatography Ag kit.

PMID- 25072380
TI  - Development of a versatile and stable internal control system for RT-qPCR assays.
AB  - RT-qPCR, an established method for the detection of RNA viruses, requires
      internal RNA controls for the correct interpretation of PCR results. Robust and
      versatile RT-PCR controls can be achieved for example by packaging RNA into a
      virus-derived protein shell. In this study a MS2-based internal control system
      was developed, that allows stable and universal packing of different RNAs into
      non-infectious, non-lytic MS2-based viral like particles (VLPs). Two competitive
      internal controls for a hantavirus assay and a Crimean-Congo Hemorrhagic Fever
      Virus (CCHFV) assay were cloned for the expression of VLPs. The expression of
      VLPs containing the RNA of interest could be induced with arabinose in
      Escherichia coli. The VLPs proved to be temperature resistant and could be frozen
      and thawed several times without degradation. Distinction of IC RNA from the
      target RNA was facilitated by a clear shift in the melting temperature or by
      specific hybridization signals. Furthermore, target and IC PCR amplification
      could be easily distinguished by their size in gel-electrophoretic analyses.
      Limits of detection were determined, demonstrating that the application of the IC
      did not reduce the sensitivity of the target RT-qPCR reactions. The system can be
      adapted to nearly any required sequence, resulting in a highly flexible method
      with broad range applications. 

PMID- 25072381
TI  - Coagulation state in patients with Crohn's disease: the effect of infliximab
      therapy.
AB  - BACKGROUND: Growing evidence has shown that coagulation processes play an
      important role in disease pathogenesis and/or disease progression in patients
      with inflammatory bowel disease. However, no study has ever focused on the
      possible influence of infliximab (IFX) therapy on the coagulation status in
      patients with Crohn's disease (CD). OBJECTIVE: To investigate the difference in
      the coagulation biomarkers between the CD patients and the control participants,
      and evaluate the impact of IFX usage on the coagulation status of CD patients.
      PATIENTS AND METHODS: A retrospective study that included a case-control study
      and a self-control study was designed. The medical records of CD patients and
      control participants were evaluated according to the inclusion and exclusion
      criteria. The results of laboratory tests including blood routine, coagulation, D
      dimer, C-reactive protein, and erythrocyte sedimentation rate were retrieved to
      assess the coagulation state. RESULTS: In the case-control study, almost all the
      parameters showed a statistically significant difference between the CD patients
      and the control participants, except for activated partial thromboplastin time
      and thrombin time (the P value ranged from 0.000 to 0.002). Most of the values of
      the parameters reverted to normal over time during IFX therapy in the self
      control study. Moreover, the fibrinogen concentration decreased obviously after
      IFX infusion (P=0.000) and the D-dimer concentration also decreased obviously by
      about half of the start value after IFX usage (P=0.018). CONCLUSION: IFX therapy
      could ameliorate the hypercoagulable state in patients with CD.

PMID- 25072382
TI  - Systematic review and bivariate/HSROC random-effect meta-analysis of
      immunochemical and guaiac-based fecal occult blood tests for colorectal cancer
      screening.
AB  - BACKGROUND: Current literature evidences higher accuracy of immunological (iFOBT)
      vis-a-vis guaiac-based (gFOBT) fecal occult blood tests for colorectal cancer
      (CRC) screening. Few well-designed head-to-head comparisons exist. AIM: This meta
      analysis assesses the performances of two iFOBTs compared with an established
      gFOBT using colonoscopy as the gold standard. METHODS: We mobilized a bivariate
      and a hierarchical summary receiver operating characteristic (HSROC) model.
      Positive likelihood ratio (LR) and negative likelihood ratio (LR) and diagnostic
      odds ratios were back-calculated. We constructed bivariate credibility ellipses
      in the HSROC space and calculated areas under the curve to obtain a global
      measure of test performance. Estimates are presented at 95% credibility levels.
      RESULTS: We included and analyzed 21 studies. OC-Sensor was the best test for CRC
      screening, with high sensitivity (0.87; 95% credibility interval: 0.73-0.95) and
      specificity (0.93; 95% credibility interval: 0.84-0.96), optimal LR (12.01) and
      LR (0.14), and a high diagnostic odds ratio (88.05). Bivariate credibility
      ellipses showed OC-Sensor's dominance over Hemoccult (sensitivity: 0.47; 95%
      credibility interval: 0.37-0.58; specificity: 0.93; 95% credibility interval:
      0.91-0.95). CONCLUSION: Our findings support the use of OC-Sensor for CRC
      detection. The diagnostic estimates obtained may be extended to derive model
      parameters for economic decision models and to offer insight for future clinical
      and public health decision making. Our findings could influence the future of
      FOBTs within the CRC screening arsenal.

PMID- 25072383
TI  - Pancreatic intubation facilitated by methylene blue injection decreases the risk
      for postpapillectomy acute pancreatitis.
AB  - OBJECTIVES: Endoscopic snare papillectomy (ESP) is a viable alternative to
      surgical treatment of ampullary adenomas and T1N0 stage ampullary carcinomas. The
      main drawback of this technique is the high risk of acute pancreatitis post
      procedure.The aim of this study was to assess the efficacy, safety, and long-term
      results of this procedure, and to determine whether routine pancreatic intubation
      facilitated by intraductal methylene blue (MB) injection reduces the risk for
      pancreatitis. PATIENTS AND METHODS: Between 2004 and 2011, 56 consecutive
      patients underwent ESP. Before resection, the pancreatic duct was cannulated, and
      MB was injected intraductally to facilitate stent placement after ampullectomy.
      RESULTS: ESP was performed en bloc in 45 patients with histological findings of
      low-grade dysplasia (39%), high-grade dysplasia (25%), carcinoma (32.5%), and
      others (3.5%). The morbidity rate was 19.5%: acute pancreatitis (n=6), bleeding
      (n=4), perforation (n=1), and sepsis (n=1). Pancreatic intubation was performed
      in 89% of the patients. Postprocedure pancreatitis occurred significantly less in
      the patients with a pancreatic stent than in those without: 3/49 versus 3/6,
      P=0.013. ESP was considered as curative in 39 patients (75%). Of the 12
      recurrences (25%), 10 were managed endoscopically, but with higher morbidity
      (acute pancreatitis=40%). CONCLUSION: Endoscopic papillectomy is safe and
      effective in the hands of experts. Pancreatic-duct stent placement in fewer
      cannulation attempts could be facilitated by injection of MB before papillectomy,
      and this decreases the risk for postprocedure pancreatitis. Recurrences can be
      managed endoscopically, but with a higher risk for pancreatitis.

PMID- 25072384
TI  - Renal dysfunction associated with telaprevir-containing triple therapy for
      chronic hepatitis C: is early prediction possible?
AB  - INTRODUCTION: Renal dysfunction has recently been described as a potential
      complication of tritherapy with telaprevir (TVR) in patients with chronic
      hepatitis C. This study aimed to identify predictive factors for and consequences
      of TVR-associated renal dysfunction. PATIENTS AND METHODS: A retrospective
      prospective study was carried out in 96 patients with chronic hepatitis C,
      genotype 1, treated with TVR-based tritherapy in 2012-2013, in whom regular serum
      creatinine measurements were performed during the first 12 weeks of treatment.
      The patients received standard doses of peginterferon, ribavirin and TVR (2250
      mg/day). The estimated glomerular filtration rate (eGFR) was calculated using the
      Modification of Diet in Renal Disease formula. RESULTS: eGFR decreased
      significantly from baseline at weeks 4, 8 and 12, the mean maximum decrease being
      22.0+/-23.6 ml/min, with a significant correlation between baseline and minimum
      eGFR (r=0.58, P<10), stronger between week 2 and minimum eGFR in the subgroup of
      62 patients in whom creatinine measurement was performed at week 2. Thirteen
      patients had an eGFR below 60 ml/min during treatment. Age and baseline eGFR were
      independent predictors of eGFR below 60 ml/min in the entire population, and only
      week 2 eGFR when available. The decrease in haemoglobin was significantly
      correlated with the decrease in eGFR. Age, baseline haemoglobin and the maximum
      variation in eGFR were independent predictors for minimum haemoglobin. The
      patients with decreased eGFR had more severe anaemia, and received more blood
      transfusions and erythropoietin. Renal dysfunction regressed in all patients
      after stopping TVR. CONCLUSION: The reversible decrease in eGFR in patients
      receiving TVR-containing tritherapy can be predicted early, possibly allowing
      measures aimed at preventing anaemia.

PMID- 25072385
TI  - Single parameter or index to predict liver injury?

PMID- 25072386
TI  - Early diagnosis of autoimmune hepatitis on the basis of demographic and
      biochemical parameters.

PMID- 25072388
TI  - Intraoperative near-infrared imaging can distinguish cancer from normal tissue
      but not inflammation.
AB  - INTRODUCTION: Defining tumor from non-tumor tissue is one of the major challenges
      of cancer surgery. Surgeons depend on visual and tactile clues to select which
      tissues should be removed from a patient. Recently, we and others have
      hypothesized near-infrared (NIR) imaging can be used during surgery to
      differentiate tumors from normal tissue. METHODS: We enrolled 8 canines and 5
      humans undergoing cancer surgery for NIR imaging. The patients were injected with
      indocyanine green (ICG), an FDA approved non-receptor specific NIR dye that
      accumulates in hyperpermeable tissues, 16-24 hours prior to surgery. During
      surgery, NIR imaging was used to discriminate the tumor from non-tumor tissue.
      RESULTS: NIR imaging identified all tumors with a mean signal-to-background ratio
      of 6.7. Optical images were useful during surgery in discriminating normal tissue
      from cancer. In 3 canine cases and 1 human case, the tissue surrounding the tumor
      was inflamed due to obstruction of the vascular supply due to mass effect. In
      these instances, NIR imaging could not distinguish tumor tissue from tissue that
      was congested, edematous and did not contain cancer. CONCLUSIONS: This study
      shows that NIR imaging can identify tumors from normal tissues, provides
      excellent tissue contrast, and it facilitates the resection of tumors. However,
      in situations where there is significant peritumoral inflammation, NIR imaging
      with ICG is not helpful. This suggests that non-targeted NIR dyes that accumulate
      in hyperpermeable tissues will have significant limitations in the future, and
      receptor-specific NIR dyes may be necessary to overcome this problem.

PMID- 25072389
TI  - Non-transferrin-bound iron assay system utilizing a conventional automated
      analyzer.
AB  - BACKGROUND: Iron is an essential metal in the body, but its excessive
      accumulation causes damage in various organs through free radical production.
      Iron homeostasis is therefore tightly regulated. However, when iron balance
      collapses, such as in prolonged transfusion, transferrin (Tf) is fully saturated
      and non-Tf-bound iron (NTBI) appears in the serum. Monitoring serum NTBI levels
      is therefore crucial in the assessment of the clinical status of patients with
      iron overload, since NTBI is associated with cellular and organ damage. Several
      methods for NTBI determination have been reported, but these are extremely
      complicated and very few laboratories can quantify NTBI at present. METHODS: We
      established a novel assay system utilizing automated analyzers that are widely
      used in clinical laboratories for diagnostic testing. In this assay, NTBI is
      chelated by nitrilotriacetic acid (NTA), after which the iron is reduced and
      transferred to nitroso-PSAP, a chromogen. RESULTS: The assay shows excellent
      linearity, reproducibility, and compatibility with HPLC, one of the most reliable
      conventional methods for NTBI quantification. CONCLUSIONS: Our novel method for
      NTBI measurement is high-throughput and may be a useful and powerful tool in the
      study of the physiological and clinical importance of NTBI.

PMID- 25072391
TI  - Decoding and encoding of visual patterns using magnetoencephalographic data
      represented in manifolds.
AB  - Visual decoding and encoding are crucial aspects in investigating the
      representation of visual information in the human brain. This paper proposes a
      bidirectional model for decoding and encoding of visual stimulus based on
      manifold representation of the temporal and spatial information extracted from
      magnetoencephalographic data. In the proposed decoding process, principal
      component analysis is applied to extract temporal principal components (TPCs)
      from the visual cortical activity estimated by a beamforming method. The spatial
      distribution of each TPC is in a high-dimensional space and can be mapped to the
      corresponding spatiotemporal component (STC) on a low-dimensional manifold. Once
      the linear mapping between the STC and the wavelet coefficients of the stimulus
      image is determined, the decoding process can synthesize an image resembling the
      stimulus image. The encoding process is performed by reversing the mapping or
      transformation in the decoding model and can predict the spatiotemporal brain
      activity from a stimulus image. In our experiments using visual stimuli
      containing eleven combinations of checkerboard patches, the information of
      spatial layout in the stimulus image was revealed in the embedded manifold. The
      correlation between the reconstructed and original images was 0.71 and the
      correlation map between the predicted and original brain activity was highly
      correlated to the map between the original brain activity for different stimuli
      (r=0.89). These results suggest that the temporal component is important in
      visual processing and manifolds can well represent the information related to
      visual perception. 

PMID- 25072390
TI  - Obesity gene NEGR1 associated with white matter integrity in healthy young
      adults.
AB  - Obesity is a crucial public health issue in developed countries, with
      implications for cardiovascular and brain health as we age. A number of commonly
      carried genetic variants are associated with obesity. Here we aim to see whether
      variants in obesity-associated genes--NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5,
      FAIM2, SEC16B, ETV5, BDNF-AS, ATXN2L, ATP2A1, KCTD15, and TNN13K--are associated
      with white matter microstructural properties, assessed by high angular resolution
      diffusion imaging (HARDI) in young healthy adults between 20 and 30 years of age
      from the Queensland Twin Imaging study (QTIM). We began with a multi-locus
      approach testing how a number of common genetic risk factors for obesity at the
      single nucleotide polymorphism (SNP) level may jointly influence white matter
      integrity throughout the brain and found a wide spread genetic effect. Risk
      allele rs2815752 in NEGR1 was most associated with lower white matter integrity
      across a substantial portion of the brain. Across the area of significance in the
      bilateral posterior corona radiata, each additional copy of the risk allele was
      associated with a 2.2% lower average FA. This is the first study to find an
      association between an obesity risk gene and differences in white matter
      integrity. As our subjects were young and healthy, our results suggest that NEGR1
      has effects on brain structure independent of its effect on obesity.

PMID- 25072393
TI  - Rapid in situ detection of ultratrace 2,4-dinitrotoluene solids by a sandwiched
      paper-like electrochemical sensor.
AB  - This work reported the rapid in situ detection of ultratrace 2,4-dinitrotoluene
      (DNT) solids on various substrates by a sandwiched paper-like electrochemical
      sensor. The sensor, prepared by a simple electroless deposition method without
      using special instruments, possessed a unique thin-film structure of an insulated
      polyvinylidene fluoride (PVDF) membrane in between two gold (Au) conducting
      layers. The resulting gold-PVDF sandwich (GPVDFS) array exhibited excellent
      flexibility, porosity and electrochemical performance as a highly integrated dual
      electrode sensor platform. The infiltration of nonvolatile ionic liquid (IL)
      electrolytes containing ferrocene (Fc) into the GPVDFS array produced a paper
      like electrochemical sensor, which can directly detect ultratrace DNT solids on
      various substrate surfaces (e.g., plant leaves, gloves and metal knives) with
      detection limit as low as 0.33 ng/mm(2). The critical role of Fc in the detection
      of DNT at this dual-electrode sensor was explored. The compensating
      electrochemical oxidation of Fc at the counter/reference electrode was found to
      be essential to the reduction of DNT at the working electrode when IL
      electrolytes were employed. The present work thus demonstrated the promising
      applications of paper-based porous electrode arrays in developing IL-based
      electrochemical sensors for the in situ detection of analyte solids in
      complicated environments. 

PMID- 25072394
TI  - Thermodynamic controls on the kinetics of microbial low-pH Fe(II) oxidation.
AB  - Acid mine drainage (AMD) is a major worldwide environmental threat to surface and
      groundwater quality. Microbial low-pH Fe(II) oxidation could be exploited for
      cost-effective AMD treatment; however, its use is limited because of
      uncertainties associated with its rate and ability to remove Fe from solution. We
      developed a thermodynamic-based framework to evaluate the kinetics of low-pH
      Fe(II) oxidation. We measured the kinetics of low-pH Fe(II) oxidation at five
      sites in the Appalachian Coal Basin in the US and three sites in the Iberian
      Pyrite Belt in Spain and found that the fastest rates of Fe(II) oxidation
      occurred at the sites with the lowest pH values. Thermodynamic calculations
      showed that the Gibbs free energy of Fe(II) oxidation (DeltaG(oxidation)) was
      also most negative at the sites with the lowest pH values. We then conducted two
      series of microbial Fe(II) oxidation experiments in laboratory-scale chemostatic
      bioreactors operated through a series of pH values (2.1-4.2) and found the same
      relationships between Fe(II) oxidation kinetics, DeltaG(oxidation), and pH.
      Conditions that favored the fastest rates of Fe(II) oxidation coincided with
      higher Fe(III) solubility. The solubility of Fe(III) minerals, thus plays an
      important role on Fe(II) oxidation kinetics. Methods to incorporate microbial low
      pH Fe(II) oxidation into active and passive AMD treatment systems are discussed
      in the context of these findings. This study presents a simplified model that
      describes the relationship between free energy and microbial kinetics and should
      be broadly applicable to many biogeochemical systems.

PMID- 25072392
TI  - Impact of autocorrelation on functional connectivity.
AB  - Although the impact of serial correlation (autocorrelation) in residuals of
      general linear models for fMRI time-series has been studied extensively, the
      effect of autocorrelation on functional connectivity studies has been largely
      neglected until recently. Some recent studies based on results from economics
      have questioned the conventional estimation of functional connectivity and argue
      that not correcting for autocorrelation in fMRI time-series results in "spurious"
      correlation coefficients. In this paper, first we assess the effect of
      autocorrelation on Pearson correlation coefficient through theoretical
      approximation and simulation. Then we present this effect on real fMRI data. To
      our knowledge this is the first work comprehensively investigating the effect of
      autocorrelation on functional connectivity estimates. Our results show that
      although FC values are altered, even following correction for autocorrelation,
      results of hypothesis testing on FC values remain very similar to those before
      correction. In real data we show this is true for main effects and also for group
      difference testing between healthy controls and schizophrenia patients. We
      further discuss model order selection in the context of autoregressive processes,
      effects of frequency filtering and propose a preprocessing pipeline for
      connectivity studies. 

PMID- 25072395
TI  - Pressure-induced transformations in LiCl-H2O at 77 K.
AB  - A systematic study of the properties of high-density amorphous ice (HDA) in the
      presence of increasing amounts of salt is missing, especially because it is
      challenging to avoid ice crystallization upon cooling the pressurized liquid. In
      order to be able to study HDA also in the presence of small amounts of salt, we
      have investigated the transformation behaviour of quenched aqueous LiCl solutions
      (mole fraction x < 0.25) upon pressurization in a piston-cylinder setup at 77 K.
      The sample properties were characterized by in situ dilatometry under high
      pressure conditions and after recovery by ex situ powder X-ray diffraction (XRD)
      and differential scanning calorimetry (DSC) at ambient pressure. Two regimes can
      be identified, with a rather sharp switch at about x = 0.12. At x < 0.12 the
      samples show the phenomenology also known for pure water samples. They are
      composed mainly of hexagonal ice (Ih) and experience pressure-induced
      amorphization to HDA at P > 1 GPa. The observed densification is consistent with
      the idea that a freeze concentrated LiCl solution of x = 0.14 (R = 6) segregates,
      which transforms to the glassy state upon cooling, and that the densification is
      only due to the Ih -> HDA transition. Also the XRD patterns and DSC scans are
      almost unaffected by the presence of the segregated glassy LiCl solution. Upon
      heating at ambient pressure HDA experiences the polyamorphic transition to low
      density amorphous ice (LDA) at ~120 K, even at x ~ 0.10. Based on the latent heat
      evolved in the transition we suggest that almost all water in the sample
      transforms to an LDA-like state, even the water in the vicinity of the ions. The
      glassy LiCl solution acts as a spectator that does not shift the transformation
      temperature significantly and experiences a glass-to-liquid transition at ~140 K
      prior to the crystallization to cubic ice. By contrast, at x > 0.12 the
      phenomenology completely changes and is now dominated by the salt. Hexagonal ice
      no longer forms upon quenching the LiCl solution, but instead LDA forms. A broad
      pressure-induced transformation at >0.6 GPa can be attributed to the
      densification of LDA, the glassy LiCl solution and/or glassy hydrates. 

PMID- 25072398
TI  - Laparoscopic sleeve gastrectomy as revisional surgery for adjustable gastric band
      erosion.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been increasingly adopted
      as a revisional surgery for failed gastric banding. However, little information
      is available regarding the outcome of revisional LSG for band erosion. MATERIALS
      AND METHODS: A retrospective database analysis was performed to study LSG as
      revisional surgery for band erosion. For staged revision, we waited a minimum of
      3 months after band removal, and for single-stage revision, the band was removed
      by gastrotomy, and sleeve gastrectomy was performed at the same time. Main
      outcome measures were success rates of therapeutic strategies, morbidity, and
      mortality rates, length of stay, and body mass index (BMI) (percentage excess
      weight loss [%EWL]) before and after revision. RESULTS: From March 2011 to
      February 2013, 9 female patients underwent revisional LSG. Average age was 34.7
      years. Six patients underwent a staged procedure, and the other 3 underwent a
      single-stage revision. Among the 6 staged patients, eroded bands had been removed
      by laparoscopy in 4 and by endoscopy in 2 without complications. Their LSGs were
      performed at a median of 4.4 months after band removal. Another 2 patients
      underwent single-stage revision. In the last patient, band erosion was
      incidentally found during a revisional LSG for insufficient weight loss. No
      mortality occurred. There were one stenosis and two proximal leaks. Two patients
      with leak underwent total gastrectomy and fistulojejunostomy. After a mean follow
      up of 19.1 months, all 9 patients exhibited weight loss. The mean (+/-standard
      deviation [SD]) pre- and post-LSG BMIs were 34.0+/-4.4 and 25.6+/-2.1 kg/m(2),
      respectively, and their mean (+/-SD) %EWL from prebanding was 86.8+/-10.1%.
      Revisional LSG resulted in a further median %EWL of 28.0% (range, 7.9%-68.9%)
      versus weight at time of band removal. CONCLUSIONS: Revisional LSG after band
      erosion was found to be feasible and effective. However, it is prone to severe
      complication. In selected cases of band erosion, LSG can be performed at the time
      of band removal in a single stage.

PMID- 25072396
TI  - Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after
      vaccination: a phase 3 randomized, controlled trial in children and young infants
      at 11 African sites.
AB  - BACKGROUND: A malaria vaccine could be an important addition to current control
      strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01
      vaccine during 18 mo following vaccination at 11 African sites with varying
      malaria transmission. METHODS AND FINDINGS: 6,537 infants aged 6-12 wk and 8,923
      children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or
      comparator vaccine. VE against clinical malaria in children during the 18 mo
      after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to
      77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1
      (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe
      malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI
      15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively
      (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per
      protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against
      severe malaria, malaria hospitalization, or all-cause hospitalization. Post
      vaccination anti-circumsporozoite antibody geometric mean titer varied from 348
      to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per
      protocol). VE waned over time in both age categories (Schoenfeld residuals
      p<0.001). The number of clinical and severe malaria cases averted per 1,000
      children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49,
      respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37,
      respectively (ITT). Meningitis was reported as a serious adverse event in
      16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the
      RTS,S/AS01 and control groups, respectively. CONCLUSIONS: RTS,S/AS01 prevented
      many cases of clinical and severe malaria over the 18 mo after vaccine dose 3,
      with the highest impact in areas with the greatest malaria incidence. VE was
      higher in children than in infants, but even at modest levels of VE, the number
      of malaria cases averted was substantial. RTS,S/AS01 could be an important
      addition to current malaria control in Africa. TRIAL REGISTRATION:
      www.ClinicalTrials.gov NCT00866619 Please see later in the article for the
      Editors' Summary.

PMID- 25072397
TI  - Immune regulatory properties of CD117(pos) amniotic fluid stem cells vary
      according to gestational age.
AB  - Amniotic Fluid Stem (AFS) cells are broadly multipotent fetal stem cells derived
      from the positive selection and ex vivo expansion of amniotic fluid CD117/c
      kit(pos) cells. Considering the differentiation potential in vitro toward cell
      lineages belonging to the three germ layers, AFS cells have raised great interest
      as a new therapeutic tool, but their immune properties still need to be assessed.
      We analyzed the in vitro immunological properties of AFS cells from different
      gestational age in coculture with T, B, and natural killer (NK) cells.
      Nonactivated (resting) first trimester-AFS cells showed lower expression of HLA
      class-I molecules and NK-activating ligands than second and third trimester-AFS
      cells, whose features were associated with lower sensitivity to NK cell-mediated
      lysis. Nevertheless, inflammatory priming with interferon gamma (IFN-gamma) and
      tumor necrosis factor alpha (TNF-alpha) enhanced resistance of all AFS cell types
      to NK cytotoxicity. AFS cells modulated lymphocyte proliferation in a different
      manner according to gestational age: first trimester-AFS cells significantly
      inhibited T and NK cell proliferation, while second and third trimester-AFS cells
      were less efficient. In addition, only inflammatory-primed second trimester-AFS
      cells could suppress B cell proliferation, which was not affected by the first
      and third trimester-AFS cells. Indolamine 2,3 dioxygenase pathway was
      significantly involved only in T cell suppression mediated by second and third
      trimester-AFS cells. Overall, this study shows a number of significant
      quantitative differences among AFS cells of different gestational age that have
      to be considered in view of their clinical application. 

PMID- 25072399
TI  - Berberine promotes glucose consumption independently of AMP-activated protein
      kinase activation.
AB  - Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP
      activated protein kinase (AMPK) pathway has been proposed as mechanism for
      berberine's action. This study aimed to examine whether AMPK activation was
      necessary for berberine's glucose-lowering effect. We found that in HepG2
      hepatocytes and C2C12 myotubes, berberine significantly increased glucose
      consumption and lactate release in a dose-dependent manner. AMPK and acetyl
      coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 umol/L
      berberine. Nevertheless, berberine was still effective on stimulating glucose
      utilization and lactate production, when the AMPK activation was blocked by (1)
      inhibition of AMPK activity by Compound C, (2) suppression of AMPKalpha
      expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing
      dominant-negative forms of AMPKalpha1/alpha2. To test the effect of berberine on
      oxygen consumption, extracellular flux analysis was performed in Seahorse XF24
      analyzer. The activity of respiratory chain complex I was almost fully blocked in
      C2C12 myotubes by berberine. Metformin, as a positive control, showed similar
      effects as berberine. These results suggest that berberine and metformin promote
      glucose metabolism by stimulating glycolysis, which probably results from
      inhibition of mitochondrial respiratory chain complex I, independent of AMPK
      activation. 

PMID- 25072401
TI  - Canine hip dysplasia: phenotypic scoring and the role of estimated breeding value
      analysis.
AB  - Canine hip dysplasia (CHD) is a developmental orthopaedic disease of the
      coxofemoral joints with a multifactorial mode of inheritance. Multiple gene
      effects are influenced by environmental factors; therefore, it is unlikely that a
      simple genetic screening test with which to identify susceptible individuals will
      be developed in the near future. In the absence of feasible methods for
      objectively quantifying clinical CHD, radiographic techniques have been developed
      and widely used to identify dogs for breeding which are less affected by the
      disease. A hip-extended ventrodorsal view of the pelvis has been traditionally
      used to identify dogs with subluxation and/or osteoarthritis of the coxofemoral
      joints. More recently, there has been emphasis on the role of coxofemoral joint
      laxity as a determinant of CHD and methods have been developed to measure passive
      hip laxity. Though well-established worldwide, the effectiveness of traditional
      phenotypic scoring schemes in reducing the prevalence of CHD has been variable.
      The most successful implementation of traditional CHD scoring has occurred in
      countries or breeding colonies with mandatory scoring and open registries with
      access to pedigree records. Several commentators have recommended that for
      quantitative traits like CHD, selection of breeding stock should be based on
      estimated breeding values (EBV) rather than individual hip score/grade. The EBV
      is a reflection of the genetic superiority of an animal compared to its
      counterparts and is calculated from the phenotype of an individual and its
      relatives and their pedigree relationship. Selecting breeding stock on the basis
      of a dog's genetic merit, ideally based on a highly predictive phenotype, will
      confer the breeder with greater selection power, accelerate genetic improvement
      towards better hip conformation and thus more likely decrease the prevalence of
      CHD. 

PMID- 25072403
TI  - Elusive transmetalation intermediate in copper-catalyzed conjugate additions:
      direct NMR detection of an ethyl group attached to a binuclear phosphoramidite
      copper complex.
AB  - Copper-catalyzed asymmetric conjugate addition reactions are a very powerful and
      widely applied method for enantioselective carbon-carbon bond formation. However,
      structural and mechanistic insight into these famous reactions has been very
      limited so far. In this article, the first direct experimental detection of
      transmetalation intermediates in copper-catalyzed reactions is presented. Special
      combinations of (1)H,(31)P HMBC spectra allow for the identification of complexes
      with chemical bonds between the alkyl groups and the copper complexes. For the
      structural characterization of these transmetalation intermediates, a special
      approach is applied, in which samples using enantiopure ligands are compared with
      samples using enantiomeric mixtures of ligands. It is experimentally proven, for
      the first time, that the dimeric copper complex structure is retained upon
      transmetalation, providing an intermediate with mixed trigonal/tetrahedral
      coordination on the copper atoms. In addition, monomeric intermediates with one
      ligand, but no intermediates with two ligands, are detected. These experimental
      results, in combination with the well-known optimal ligand-to-copper ratio of 2:1
      in synthetic applications, allow us to propose that a binuclear transmetalation
      intermediate is the reactive species in copper-catalyzed asymmetric conjugate
      addition reactions. This first direct experimental insight into the structure of
      the transmetalation intermediate is expected to support the mechanistic and
      theoretical understanding of this important class of reactions and to enable
      their further synthetic development. In addition, the special NMR approach
      presented here for the identification and characterization of intermediates below
      the detection limit of (1)H NMR spectra can be applied also to other classes of
      catalyses. 

PMID- 25072402
TI  - Children's separation anxiety scale (CSAS): psychometric properties.
AB  - This study describes the psychometric properties of the Children's Separation
      Anxiety Scale (CSAS), which assesses separation anxiety symptoms in childhood.
      Participants in Study 1 were 1,908 schoolchildren aged between 8 and 11.
      Exploratory factor analysis identified four factors: worry about separation,
      distress from separation, opposition to separation, and calm at separation, which
      explained 46.91% of the variance. In Study 2, 6,016 children aged 8-11
      participated. The factor model in Study 1 was validated by confirmatory factor
      analysis. The internal consistency (alpha = 0.82) and temporal stability (r =
      0.83) of the instrument were good. The convergent and discriminant validity were
      evaluated by means of correlations with other measures of separation anxiety,
      childhood anxiety, depression and anger. Sensitivity of the scale was 85% and its
      specificity, 95%. The results support the reliability and validity of the CSAS. 

PMID- 25072404
TI  - A qualitative systematic review of patients' experiences of acupuncture.
AB  - OBJECTIVES: To present the results of a systematic review of studies on
      acupuncture patients' health beliefs and treatment experiences. SEARCH STRATEGY:
      The search was conducted using CINAHL, PubMed, Ovid MEDLINE, ISI Web of Science,
      and PsychINFO for qualitative and mixed-methods studies expressing the voice of
      acupuncture patients. Reference lists of relevant articles were also searched.
      The review was restricted to studies published in English. DATA COLLECTION AND
      ANALYSIS: Study selection, quality appraisal, and data extraction were performed
      sequentially. Quality was appraised using the Joanna Briggs Institute Qualitative
      Assessment and Review Instrument, and the Dedoose mixed methods tool was used in
      data management and analysis. RESULTS: Four overarching themes were identified:
      reasons for using acupuncture, treatment experiences, treatment outcomes, and
      therapeutic model. CONCLUSIONS: Patients' reasons for using acupuncture are
      diverse and include dissatisfaction with conventional medicine and attraction to
      holistic and empowering models of healthcare. Treatment is thought to relieve
      symptoms of the presenting concern and a range of other effects that improve well
      being. This review highlights the need to improve understanding of patients'
      health-seeking behaviors and how individually meaningful treatment outcomes may
      be understood and assessed, particularly within complementary and alternative
      medicine.

PMID- 25072406
TI  - Genetic risk factors of atherothrombosis.
AB  - Atherothrombosis is a preventable and multifaceted pathological disorder whose
      pathogenesis involves a large number of biological pathways such as lipid and
      hormonal metabolism, inflammation, and hemostasis. Although it has been known for
      a long time that atherosclerosis has a sizable hereditary component, research in
      the field of genetics of cardiovascular disease is still ongoing, with doubts
      often outweighing certainties. A large amount of evidence gathered so far allows
      to identify at least 5 potential important pathways that can be specifically
      targeted by genetic studies--lipoprotein metabolism, inflammation, the renin
      angiotensin-aldosterone system, platelet function, blood coagulation, and
      fibrinolysis. Owing to a large number of published studies that have investigated
      the role of genetic polymorphisms in the pathogenesis of atherothrombosis and its
      complications, in this review, we focused on data emerging from meta-analyses.
      The available evidence suggests that some selected polymorphisms in low-density
      lipoprotein metabolism, C-reactive protein, and blood coagulation (especially
      factor V Leiden, prothrombin G20210A polymorphism, and plasminogen activator
      inhibitor type 1 4G/5G polymorphism) deserve particular attention. Of note,
      however, it seems implausible that one single polymorphism will add much to the
      current approach of risk assessment based on conventional risk factors. A
      paradigm shift would hence be needed in the current approach to the genetics of
      atherothrombosis, wherein the investigation of entire pathways rather than
      assessment of single mutations will likely provide more useful information for
      complex conditions that involve large numbers of genes and are subjected to
      environmental regulation of gene expression and cellular phenotype.

PMID- 25072407
TI  - Multiple GO-SELEX for efficient screening of flexible aptamers.
AB  - We describe a simple, high-speed, high-throughput aptamer screening for a group
      of small molecules using graphene oxide (simple Multi-GO-SELEX) without
      immobilizing targets. The affinities of ten different ssDNA aptamers successfully
      obtained for three pesticides were in the range of 10-100 nM. Besides a specific
      aptamer for each target, we found a couple of flexible multi-target aptamers,
      which can bind with 2 or 3 different molecules. These flexible aptamers developed
      for binding with a mixture of targets are not only significant for the rapid
      screening of a group of small molecules but also offer great promise for aptamer
      based biosensor applications. 

PMID- 25072405
TI  - Telephone and in-person cognitive behavioral therapy for major depression after
      traumatic brain injury: a randomized controlled trial.
AB  - Major depressive disorder (MDD) is prevalent after traumatic brain injury (TBI);
      however, there is a lack of evidence regarding effective treatment approaches. We
      conducted a choice-stratified randomized controlled trial in 100 adults with MDD
      within 10 years of complicated mild to severe TBI to test the effectiveness of
      brief cognitive behavioral therapy administered over the telephone (CBT-T) (n =
      40) or in-person (CBT-IP) (n = 18), compared with usual care (UC) (n = 42).
      Participants were recruited from clinical and community settings throughout the
      United States. The main outcomes were change in depression severity on the
      clinician-rated 17 item Hamilton Depression Rating Scale (HAMD-17) and the
      patient-reported Symptom Checklist-20 (SCL-20) over 16 weeks. There was no
      significant difference between the combined CBT and UC groups over 16 weeks on
      the HAMD-17 (treatment effect = 1.2, 95% CI: -1.5-4.0; p = 0.37) and a
      nonsignificant trend favoring CBT on the SCL-20 (treatment effect = 0.28, 95% CI:
      -0.03-0.59; p = 0.074). In follow-up comparisons, the CBT-T group had
      significantly more improvement on the SCL-20 than the UC group (treatment effect
      = 0.36, 95% CI: 0.01-0.70; p = 0.043) and completers of eight or more CBT
      sessions had significantly improved SCL-20 scores compared with the UC group
      (treatment effect = 0.43, 95% CI: 0.10-0.76; p = 0.011). CBT participants
      reported significantly more symptom improvement (p = 0.010) and greater
      satisfaction with depression care (p < 0.001), than did the UC group. In-person
      and telephone-administered CBT are acceptable and feasible in persons with TBI.
      Although further research is warranted, telephone CBT holds particular promise
      for enhancing access and adherence to effective depression treatment.

PMID- 25072408
TI  - Functional connectivity of primary motor cortex is dependent on genetic burden in
      prodromal Huntington disease.
AB  - Subtle changes in motor function have been observed in individuals with prodromal
      Huntington disease (prHD), but the underlying neural mechanisms are not well
      understood nor is the cumulative effect of the disease (disease burden) on
      functional connectivity. The present study examined the resting-state functional
      magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex
      (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants
      with various levels of disease burden. The results showed that the strength of
      the left M1 connectivity with the ipsilateral M1 and somatosensory areas
      decreased as disease burden increased and correlated with motor symptoms.
      Weakened M1 connectivity within the motor areas was also associated with
      abnormalities in long-range connections that evolved with disease burden. In this
      study, M1 connectivity was decreased with visual centers (bilateral cuneus), but
      increased with a hub of the default mode network (DMN; posterior cingulate
      cortex). Changes in connectivity measures were associated with worse performance
      on measures of cognitive-motor functioning. Short- and long-range functional
      connectivity disturbances were also associated with volume loss in the basal
      ganglia, suggesting that weakened M1 connectivity is partly a manifestation of
      striatal atrophy. Altogether, the results indicate that the prodromal phase of HD
      is associated with abnormal interhemispheric interactions among motor areas and
      disturbances in the connectivity of M1 with visual centers and the DMN. These
      changes may, respectively, contribute to increased motor symptoms, visuomotor
      integration problems, and deficits in the executive control of movement as
      individuals approach a manifest diagnosis.

PMID- 25072409
TI  - Wavefront-guided versus non-wavefront-guided photorefractive keratectomy for
      myopia: meta-analysis of randomized controlled trials.
AB  - PURPOSE: To compare the efficacy, predictability, safety, and induced higher
      order aberrations (HOAs) between wavefront-guided and non-wavefront-guided
      photorefractive keratectomy (PRK). METHODS: The Cochrane Central Register of
      Controlled Trials, PubMED, and EMBASE were searched for randomized controlled
      trials. Trials meeting the selection criteria were quality appraised, and data
      was extracted by 2 independent authors. Measures of association were pooled
      quantitatively using meta-analytical methods. Comparisons between wavefront
      guided and non-wavefront-guided ablations were made as pooled odds ratios (ORs)
      or weighted mean differences. The pooled ORs and 95% confidence intervals (CIs)
      were computed for efficacy, safety, and predictability. The weighted mean
      differences and 95% CIs were used to compare induced HOAs. RESULTS: The study
      covered five trials involving 298 eyes. After wavefront-guided PRK, the pooled OR
      of achieving an uncorrected distance visual acuity of 20/20 (efficacy) was 1.18
      (95% CI, 0.53-2.60; p = 0.69), the pooled OR of achieving a result within +/-0.50
      diopter of the intended target (predictability) was 0.86 (95% CI, 0.40-1.84; p =
      0.70). No study reported a loss of 2 or more lines of Snellen acuity (safety)
      with either modality. In eyes with wavefront-guided PRK, the postoperative
      trefoil aberrations (mean difference -0.02; 95% CI, -0.03 to -0.00; p = 0.03)
      were significantly lower. There were no significant differences between the two
      groups in the postoperative total HOAs (mean difference -0.04; 95% CI, -0.23 to
      0.14; p = 0.63), spherical (mean difference 0.00; 95% CI, -0.08 to 0.09; p =
      0.93), and coma (mean difference -0.06; 95% CI, -0.14 to 0.03; p = 0.20)
      aberrations. CONCLUSIONS: According to the meta-analysis, wavefront-guided PRK
      offered no advantage in efficacy, predictability, or safety measures over non
      wavefront-guided PRK, although it may have induced fewer trefoil aberrations.

PMID- 25072410
TI  - Development and evaluation of cesarean section surgical training using computer
      enhanced visual learning.
AB  - BACKGROUND: Skilled performance of cesarean deliveries is essential in obstetrics
      and gynecology residency. A computer-enhanced visual learning module (CEVL
      Cesarean) was developed to teach cesarean deliveries. METHODS: An online module
      presented cesarean deliveries as a series of components using text, audio, video
      and animation. First-year residents used CEVL Cesarean and were evaluated intra
      operatively by trained raters, then provided feedback about surgical performance.
      Clinical outcomes were collected for approximately 50 cesarean deliveries for
      each resident. RESULTS: From 2010 to 2011, 12 first-year residents participated
      in the study. About 406 unique observed cesarean deliveries were analyzed.
      Procedures up to each resident's 70th case were analyzed by grouping cases in 10
      s (cases 1-10 and 11-20), or deciles. Resident performance significantly improved
      by decile [chi(2)(6) = 47.56, p < 0.001]. When examining each resident's
      performance, surgical skill acquisition plateaued by cases 21-30. Procedural
      performance, independent of resident, also improved significantly by decile
      [chi(2)(6) = 186.95, p < 0.001], plateauing by decile 4 (cases 31-40). Throughout
      the observation period, operative time decreased by 3.84 min (p = 0.006).
      CONCLUSIONS: Pre-clinical teaching using computer-based modules for cesarean
      sections is feasible to develop. Novice surgeons required at least 30 procedures
      before performing the procedure competently. When residents performed
      competently, operative time and complications decreased.

PMID- 25072411
TI  - [(C2H5)4N][U2O4(HCOO)5], an ammonium uranyl formate framework showing para- to
      ferro-electric transition: synthesis, structures, and properties.
AB  - We report an ammonium uranyl formate framework of formula
      [(C2H5)4N][U2O4(HCOO)5], prepared by using components of tetraethylammonium,
      uranyl, and formate. The compound possesses a layered structure of anionic uranyl
      formate wavy sheets and intercalated (C2H5)4N(+) cations. The sheet consists of
      pentagonal bipyramidal uranyl cations connected by equatorial anti-anti and anti
      syn HCOO(-) bridges, and it has a topology of 3(3).4(3).5(4) made of edge-sharing
      square and triangle grids. The high-temperature (HT) phase belongs to the chiral
      but nonpolar tetragonal space group P42(1)m. In the structure, one HCOO(-) is 2
      fold disordered, showing a flip motion between the two anti-syn orientations. On
      cooling, this flip motion slowed and finally froze, leading to a phase transition
      at ~200 K. The low-temperature (LT) structure is monoclinic and polar in space
      group P2(1); the cations shift, and the layers slide. Especially, the concerted
      and net shifts of the ammonium cations toward the -b direction, with respect to
      the anionic sheets, result in an estimated spontaneous polarization of 0.86 MUC
      cm(-2) in LT. The phase transition is thus para- to ferro-electric, in Aizu
      notation 42mF2, accompanied by significant, anisotropic dielectric anomalies,
      with a quite significant thermal hysteresis. Variable-temperature luminescent
      spectroscopy and differential scanning calorimetry confirmed the transition and
      provided further information. The structure-property relationship is established.

PMID- 25072412
TI  - Developmental student support in undergraduate medical education: AMEE Guide No.
      92.
AB  - Developmental student support has a focus on developing the whole person, not
      only academic and clinical competence. The positive and proactive developmental
      approach is in marked contrast to the deficit and reactive approach to student
      support which only targets identified students who are considered to be "at
      risk". The medical school is a nexus for personal development, combining the
      personal identity formation journey of early adulthood with the variety of new
      experiences in medical school. Important aspects of developmental student support
      are the development of resilience and ensuring reasonable adjustments for
      students with learning difficulties and disabilities. Careers guidance is an
      essential aspect of developmental student support, including students with doubts
      about a career in medicine and who are leaving because of poor performance.
      Developmental student support requires an organizational culture in which student
      support is considered as the responsibility of everyone, with further support
      from named personal tutors.

PMID- 25072413
TI  - Exploring functional contexts of symbiotic sustain within lichen-associated
      bacteria by comparative omics.
AB  - Symbioses represent a frequent and successful lifestyle on earth and lichens are
      one of their classic examples. Recently, bacterial communities were identified as
      stable, specific and structurally integrated partners of the lichen symbiosis,
      but their role has remained largely elusive in comparison to the well-known
      functions of the fungal and algal partners. We have explored the metabolic
      potentials of the microbiome using the lung lichen Lobaria pulmonaria as the
      model. Metagenomic and proteomic data were comparatively assessed and visualized
      by Voronoi treemaps. The study was complemented with molecular, microscopic and
      physiological assays. We have found that more than 800 bacterial species have the
      ability to contribute multiple aspects to the symbiotic system, including
      essential functions such as (i) nutrient supply, especially nitrogen, phosphorous
      and sulfur, (ii) resistance against biotic stress factors (that is, pathogen
      defense), (iii) resistance against abiotic factors, (iv) support of
      photosynthesis by provision of vitamin B12, (v) fungal and algal growth support
      by provision of hormones, (vi) detoxification of metabolites, and (vii)
      degradation of older parts of the lichen thallus. Our findings showed the
      potential of lichen-associated bacteria to interact with the fungal as well as
      algal partner to support health, growth and fitness of their hosts. We developed
      a model of the symbiosis depicting the functional multi-player network of the
      participants, and argue that the strategy of functional diversification in
      lichens supports the longevity and persistence of lichens under extreme and
      changing ecological conditions. 

PMID- 25072414
TI  - Satellite remote sensing data can be used to model marine microbial metabolite
      turnover.
AB  - Sampling ecosystems, even at a local scale, at the temporal and spatial
      resolution necessary to capture natural variability in microbial communities are
      prohibitively expensive. We extrapolated marine surface microbial community
      structure and metabolic potential from 72 16S rRNA amplicon and 8 metagenomic
      observations using remotely sensed environmental parameters to create a system
      scale model of marine microbial metabolism for 5904 grid cells (49 km(2)) in the
      Western English Chanel, across 3 years of weekly averages. Thirteen environmental
      variables predicted the relative abundance of 24 bacterial Orders and 1715 unique
      enzyme-encoding genes that encode turnover of 2893 metabolites. The genes'
      predicted relative abundance was highly correlated (Pearson Correlation 0.72, P
      value <10(-6)) with their observed relative abundance in sequenced metagenomes.
      Predictions of the relative turnover (synthesis or consumption) of CO2 were
      significantly correlated with observed surface CO2 fugacity. The spatial and
      temporal variation in the predicted relative abundances of genes coding for
      cyanase, carbon monoxide and malate dehydrogenase were investigated along with
      the predicted inter-annual variation in relative consumption or production of
      ~3000 metabolites forming six significant temporal clusters. These spatiotemporal
      distributions could possibly be explained by the co-occurrence of anaerobic and
      aerobic metabolisms associated with localized plankton blooms or sediment
      resuspension, which facilitate the presence of anaerobic micro-niches. This
      predictive model provides a general framework for focusing future sampling and
      experimental design to relate biogeochemical turnover to microbial ecology. 

PMID- 25072415
TI  - Establishment of a novel cell line for the enhanced production of recombinant
      adeno-associated virus vectors for gene therapy.
AB  - Adeno-associated viral (AAV) vectors show great promise because of their
      excellent safety profile; however, pre-existing immune responses have
      necessitated the administration of high titer AAV, posing a significant challenge
      to the advancement of gene therapy involving AAV vectors. Recombinant AAV vectors
      contain minimum viral proteins necessary for their assembly and gene delivery
      functions. During the process of AAV assembly and production, AAV vectors
      acquire, inherently and submissively, various cellular proteins, but the identity
      of these proteins is poorly characterized. We reason that by identifying host
      cell proteins inherently associated with AAV vectors we may better understand the
      contribution of cellular components to AAV vector assembly and, ultimately, may
      improve the production of AAV vectors for gene therapy. In this study, three
      serotypes of recombinant AAV, namely AAV2, AAV5, and AAV8, were investigated. We
      used liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) methods
      to identify protein composition in purified AAV vectors, confirmed protein
      identities using western blotting, and explored the potential function of
      selected proteins in AAV vector production using small hairpin (shRNA) methods.
      Using LC-MS/MS, we identified 44 AAV-associated cellular proteins including Y-box
      binding protein (YB1). We showed for the first time that the establishment of a
      novel producer cell line by introducing an shRNA sequence down-regulating YB1
      resulted in up to 45- and 9-fold increase in physical vector genome titers of
      AAV2 and AAV8, respectively, and up to 7-fold increase in AAV2 transduction
      vector genome titers. Our results revealed that YB1 gene knockdown promoted AAV2
      rep expression and vector DNA production and reduced the number of empty
      particles in AAV2 products, suggesting that YB1 plays an important role in AAV
      vector assembly by competition with adenovirus E2A and AAV capsid proteins for
      binding to the inverted terminal repeat (ITR) sequence. The significance and
      implications of our findings in future improvement of AAV production are
      discussed.

PMID- 25072416
TI  - Proportion of illness acquired by foodborne transmission for nine enteric
      pathogens in Australia: an expert elicitation.
AB  - BACKGROUND: Estimates of the burden of illness acquired from food inform public
      health policy and prioritize interventions. A key component of such estimates is
      the proportion of illnesses that are acquired by foodborne transmission. In view
      of the shortage of requisite data, these proportions are commonly obtained
      through a process known as expert elicitation. We report findings from an
      elicitation process used to assess the importance of the foodborne transmission
      route for nine pathogens in Australia, circa 2010. MATERIALS AND METHODS: Eleven
      experts were asked to estimate the proportion of illness acquired by five
      transmission routes: food, environmental, water, person, and zoonotic, together
      with a 90% certainty interval for foodborne transmission. Foodborne estimates and
      intervals from each expert were combined using both modified triangular and
      Program Evaluation and Review Technique (PERT) distributions, in @Risk version 6,
      to generate final distributions from which median estimates and 95% Credible
      Intervals (CrI) were calculated. RESULTS: Shiga toxin-producing Escherichia coli
      (STEC) was the only pathogen believed to have an important zoonotic transmission
      route, while norovirus, hepatitis A virus, non-STEC pathogenic E. coli, and
      Shigella spp. were all thought to be primarily spread from person to person.
      Foodborne transmission was the main route for Clostridium perfringens (98%, CrI:
      84-100), Listeria monocytogenes (98%, CrI: 86-100), nontyphoidal Salmonella spp.
      (72%, CrI: 50-87), and Campylobacter spp. (77%, CrI: 60-90). Foodborne estimates
      using the modified triangular distribution had wider CrI than these calculated
      using the PERT distribution. CONCLUSIONS: Foodborne proportions for most
      pathogens in this study were the same or lower than those estimated circa 2000 in
      Australia, with the greatest decline for non-STEC pathogenic E. coli. Inclusion
      of certainty intervals from experts helps to quantify the precision of foodborne
      proportions. A decline in estimates of the foodborne proportion for common
      pathogens will influence final estimates of the burden of illness acquired from
      food.

PMID- 25072417
TI  - [The SAVOR-TIMI 53 study].

PMID- 25072418
TI  - [The EXAMINE study].

PMID- 25072419
TI  - [European guidelines on diabetes, pre-diabetes and cardiovascular diseases:
      what's new?].

PMID- 25072420
TI  - [A critical appraisal of the European guidelines on diabetes, pre-diabetes and
      cardiovascular diseases].

PMID- 25072421
TI  - [Role of bone marrow-derived CD133+ stem cells in cardiac regeneration: from
      experimental to clinical trials].
AB  - Recent advances in coronary revascularization techniques have improved the
      outcomes of ischemic heart disease in both acute and chronic settings. As a
      drawback, an increase in patients with an advanced stage of ischemic
      cardiomyopathy refractory to optimal medical treatment has been observed. Among
      the therapeutic alternatives under investigation, cell therapy showed
      considerable anti-ischemic potential. Although several types of cells have been
      used, bone marrow-derived endothelial progenitor cells are among the most
      appealing therapeutic agents due to their angiogenic properties. In particular,
      endothelial progenitors expressing the transmembrane protein CD133 have been in
      vitro and in vivo extensively characterized and clinically tested. The aim of
      this paper is to discuss the translational process that allowed the clinical
      application of CD133+ endothelial progenitor cells in the context of ischemic
      cardiomyopathy. 

PMID- 25072422
TI  - [Paradigm shifts in aortic pathology: clinical and therapeutic implications.
      Clinical imaging in chronic and acute aortic syndromes. The aorta as a cause of
      cardiac disease].
AB  - Multimodal imaging plays a pivotal role in the assessment of the thoracic aorta,
      both in chronic and acute settings. Moving from improved knowledge on the
      structure and function of the aortic wall, as well as on its pathophysiology and
      histopathology, appropriate utilization of each imaging modality results into a
      better definition of the patient's need and proper treatment strategy. This
      review is aimed at highlighting the most critical aspects in this field,
      providing cardiologists with some novel clues for the imaging approach to
      patients with thoracic aortic disease. 

PMID- 25072423
TI  - [Multi-modality imaging: mycotic abscess of a pericardial patch].

PMID- 25072424
TI  - [Multidisciplinary management of patients with acute coronary syndrome and
      diabetes mellitus: from antithrombotic therapy to treatment of hyperglycemia].
AB  - Patients with diabetes mellitus (DM) and acute coronary syndromes (ACS) present a
      significantly higher risk of developing ischemic complications as compared to
      nondiabetic patients. Multiple mechanisms contribute to DM patients' enhanced
      prothrombotic status, including impaired fibrinolysis and coagulation, as well as
      endothelial and platelet dysfunction. Therefore, antithrombotic agents generally,
      and antiplatelet agents in particular, represent a logical secondary preventive
      strategy to reduce the risk of recurrent ischemic events in DM patients with ACS.
      However, DM patients often show attenuated responses to antiplatelet therapies
      for ACS patients. DM patients benefit from early coronary angiography and
      revascularization. Although randomized clinical trials have demonstrated that
      surgical revascularization is associated with an improved prognosis compared to
      percutaneous coronary intervention, a tailored revascularization strategy should
      be provided for each patient. The type of revascularization should be decided on
      the basis of SYNTAX score, surgical risk profile, and feasibility of total
      arterial revascularization in case of surgery. An accurate diagnosis and prompt
      treatment of hyperglycemia should also be provided for all patients. The present
      multidisciplinary document provides practical recommendations regarding diagnosis
      of DM and the management of hyperglycemia, from the acute phase to discharge. It
      is aimed at favoring early detection of hyperglycemia and identification of
      diabetic patients so as to provide adequate glucose control. 

PMID- 25072427
TI  - En Bloc Resection of Pulmonary Sulcus Non-small Cell Lung Cancer Invading the
      Spine: A Systematic Literature Review and Pooled Data Analysis.
AB  - OBJECTIVE: To conduct a systematic literature review and pooled data analysis
      focusing on outcome after en bloc resection of pulmonary sulcus non-small cell
      lung cancer (NSCLC) invading the spine. BACKGROUND: This rare type of NSCLC has
      historically been considered unresectable and fatal. Nowadays, carefully selected
      patients can be cured when treated surgically within a multimodality concept.
      METHODS: The MEDLINE database was searched using the PubMed engine to retrieve
      relevant articles. Corresponding authors were contacted, and shared data were
      pooled and analyzed. RESULTS: Search strategy yielded 134 articles. Six were
      relevant and nonduplicative. Four authors shared updated data on 135 patients.
      All tumors were resected en bloc with the lung, chest wall, and spine. Induction
      was administered in 85 patients (63%) and consisted of chemotherapy (n = 32),
      radiation (n = 1), or concurrent chemoradiation (n = 52). Spine resections
      included total (n = 23), hemi- (n = 94), and partial (n = 18) vertebrectomies. R0
      resection was achieved in 120 patients (89%). Adjuvant treatment was administered
      to 70 patients (52%) and included chemotherapy (n = 16), radiotherapy (n = 22),
      or chemoradiation (n = 32). Overall, 3-, 5-, and 10-year survival rates were 57%,
      43%, and 27%, respectively. Univariate analysis identified the type of resection
      (R0 vs R1/R2, P < 0.001) as significant prognostic factor among the variables
      tested (age, histology, pT/pN, type of induction/adjuvant treatment, type of
      lung/spine resection). CONCLUSIONS: Multimodality therapy including en bloc
      resection for pulmonary sulcus NSCLC invading the spine provides excellent long
      term survival in selected patients. This result establishes a benchmark against
      which the effects of new treatments can be compared in the future.

PMID- 25072428
TI  - Predicting perioperative risk and informed consent.

PMID- 25072429
TI  - Total gastrectomy risk model: data from 20,011 Japanese patients in a nationwide
      internet-based database.
AB  - OBJECTIVE: To construct a risk model for total gastrectomy outcomes using a
      nationwide Internet-based database. BACKGROUND: Total gastrectomy is a very
      common procedure in Japan. This procedure is among the most invasive
      gastrointestinal procedures and is known to carry substantial surgical risks.
      METHODS: The National Clinical Database was used to retrieve records on more than
      1,200,000 surgical cases from 3500 hospitals in 2011. After data cleanup, 20,011
      records from 1623 hospitals were analyzed for procedures performed between
      January 1, 2011, and December 31, 2011. RESULTS: The average patient age was 68.9
      years; 73.7% were male. The overall morbidity was 26.2%, with a 30-day mortality
      rate of 0.9%, in-hospital mortality rate of 2.2%, and overall operative mortality
      rate of 2.3%. The odds ratios for 30-day mortality were as follows: ASA (American
      Society of Anesthesiologists) grade 4 or 5, 9.4; preoperative dialysis
      requirement, 3.9; and platelet count less than 50,000 per microliter, 3.1. The
      odds ratios for operative mortality were as follows: ASA grade 4 or 5, 5.2;
      disseminated cancer, 3.5; and alkaline phosphatase level of more than 600 IU/L,
      3.1. The C-index of 30-day mortality and operative mortality was 0.811 (95%
      confidence interval [CI], 0.744-0.879) and 0.824 (95% CI, 0.781-0.866),
      respectively. CONCLUSIONS: We have performed the first reported risk
      stratification study for total gastrectomy, using a nationwide Internet-based
      database. The total gastrectomy outcomes in the nationwide population were
      satisfactory. The risk models that we have created will help improve the quality
      of surgical practice.

PMID- 25072430
TI  - The optimum excision margin and regional node management for primary cutaneous T3
      melanomas (2-4 mm in Thickness): a retrospective study of 1587 patients treated
      at a single center.
AB  - OBJECTIVE: To determine the optimum excision margin and nodal management for
      patients with primary cutaneous melanomas 2.01- to 4.00-mm thick (T3 melanomas).
      BACKGROUND: Currently available evidence does not reliably define the minimum
      safe excision margin and best nodal management for patients with primary
      cutaneous T3 melanomas. METHODS: A retrospective study was conducted, analyzing
      data on 1587 patients with melanomas 2.01- to 4.00-mm thick treated at a single
      center. RESULTS: A histopathologic excision margin of 8 mm or more (equivalent to
      a >=1 cm surgical margin) was associated with increased local and in-transit
      recurrence-free survival [hazard ratio (HR) = 0.54; P = 0.008] and disease-free
      survival (DFS) (HR = 0.59; P = 0.001) compared with a less than 8-mm margin. The
      <8-mm group had reduced distant recurrence-free survival (DRFS) compared with the
      8- to 16-mm group (HR = 1.63; P = 0.038). On multivariate analysis, patients with
      a positive sentinel lymph node (SLN) had significantly reduced melanoma-specific
      survival (MSS), DFS, regional node recurrence-free survival (RNRFS) and DRFS
      compared with patients with a negative SLN, unless an immediate completion lymph
      node dissection was performed. Patients in whom an SLN biopsy was not performed
      had significantly reduced MSS (HR = 2.10; P < 0.001), DFS (P < 0.001), RNRFS (P <
      0.001), and DRFS (P = 0.010) compared with patients who received an SLN biopsy.
      CONCLUSIONS: A histopathologic excision margin of 8 mm or more (corresponding to
      a >=1 cm surgical excision margin) combined with SLN biopsy (followed by an
      immediate completion lymph node dissection if positive) provided T3 melanoma
      patients with optimum local, regional, and distant disease control and resulted
      in enhanced melanoma-specific survival.

PMID- 25072431
TI  - Long-term Shifting Patterns in Quality of Life After Distal Subtotal Gastrectomy:
      Preoperative- and Healthy-based Interpretations.
AB  - OBJECTIVE: The study assessed long-term shifting patterns in quality of life
      (QoL) after distal subtotal gastrectomy relative to an estimated healthy
      population QoL (HPQoL), and compared them to shifting patterns interpreted in
      terms of a preoperative QoL baseline. BACKGROUND: QoL data from 127 gastric
      cancer patients who underwent open distal subtotal gastrectomy were obtained at
      the preoperative period and at 6, 12, 18, 24, and 36 months after surgery. QoL
      data obtained from 127 age- and sex-adjusted healthy individuals were used to
      estimate HPQoL. METHODS: The study used the European Organization for Research
      and Treatment of Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) and a gastric
      cancer module (QLQ-STO22) to assess QoL. Comparisons were made between
      preoperative-based and healthy-based interpretations of longitudinal QoL shifting
      patterns. RESULTS: Among the persistently deteriorated QoL variables indicated by
      the preoperative-based interpretation (physical functioning, role functioning,
      cognitive functioning, nausea and vomiting, dyspnea, diarrhea, dysphagia, eating
      restrictions, dry mouth, and body image), eating restrictions and body image
      concerns were the only factors indicated by a healthy-based interpretation. In
      this interpretation, financial difficulties were evident at the preoperative
      period and persisted for at least 36 months. When preoperative QoL was used as a
      baseline, decreased QoL due to financial difficulties was not revealed.
      CONCLUSIONS: Persistent QoL deterioration after distal subtotal gastrectomy is
      primarily due to financial difficulties, eating restrictions, and body image
      concerns. Preoperative-based interpretation of postoperative QoL may exaggerate
      the persistency of reduced QoL and conceal on-going QoL deterioration after
      surgery.

PMID- 25072432
TI  - Reply to Letter: "Computerized Tomography-based Diagnosis of Sarcopenia?".

PMID- 25072433
TI  - Samuel D. Gross, the Writing of American Surgical History.
AB  - OBJECTIVE: To explore the details of Samuel D. Gross's achievements as America's
      foremost historian of medicine in the mid-nineteenth century. BACKGROUND: The
      life of Samuel D. Gross, the most renowned of the nation's surgeons in the
      nineteenth century, has been extensively researched and celebrated. Despite the
      long-standing interest in Gross's accomplishments, there is an important and
      influential aspect of his career that has been forgotten. Gross was the country's
      first surgical historian and his boosting of the popular image of the knife
      bearer was crucial to shaping the future of the craft, in particular surgery's
      rise as a respected specialty within the whole of medicine. METHODS: An analysis
      of the published medical literature and unpublished documents relating to Samuel
      D. Gross and his status as the country's earliest historian of surgery. RESULTS:
      At a time when surgery was not considered a separate branch of medicine but a
      mere technical mode of treatment, Gross's efforts in medical and surgical history
      provided a much needed boost to surgeons in their pursuit of self-confidence and
      self-respect. CONCLUSIONS: Although Gross's accomplishments as a medical
      historian have been overlooked, it is undeniable that he was America's pioneer
      surgical historian and, as such, afforded surgeons their earliest measure of self
      esteem, a critical attribute that was indispensable for the rise of surgery as a
      distinguished profession.

PMID- 25072434
TI  - Reply to Letter: "Preoperative Endoscopic Nasobiliary Drainage in Patients With
      Suspected Hilar Cholangiocarcinoma; Better Than Endoscopic or Percutaneous
      Biliary Drainage?".

PMID- 25072435
TI  - A qualitative evaluation of the barriers and facilitators toward implementation
      of the WHO surgical safety checklist across hospitals in England: lessons from
      the "Surgical Checklist Implementation Project".
AB  - OBJECTIVES: To evaluate how the World Health Organization (WHO) surgical safety
      checklist was implemented across hospitals in England; to identify barriers and
      facilitators toward implementation; and to draw out lessons for implementing
      improvement initiatives in surgery/health care more generally. BACKGROUND: The
      WHO checklist has been linked to improved surgical outcomes and teamwork, yet we
      know little about the factors affecting its successful uptake. METHODS: A
      longitudinal interview study with operating room personnel was conducted across a
      representative sample of 10 hospitals in England between March 2010 and March
      2011. Interviews were audio recorded over the phone. Interviewees were asked
      about their experience of how the checklist was introduced and the factors that
      hindered or aided this process. Transcripts were submitted to thematic analysis.
      RESULTS: A total of 119 interviews were completed. Checklist implementation
      varied greatly between and within hospitals, ranging from preplanned/phased
      approaches to the checklist simply "appearing" in operating rooms, or staff
      feeling it had been imposed. Most barriers to implementation were specific to the
      checklist itself (eg, perceived design issues) but also included problematic
      integration into preexisting processes. The most common barrier was resistance
      from senior clinicians. The facilitators revealed some positive steps that can
      been taken to prevent/address these barriers, for example, modifying the
      checklist, providing education/training, feeding-back local data, fostering
      strong leadership (particularly at attending level), and instilling
      accountability. CONCLUSIONS: We identified common themes that have aided or
      hindered the introduction of the WHO checklist in England and have translated
      these into recommendations to guide the implementation of improvement initiatives
      in surgery and wider health care systems.

PMID- 25072436
TI  - The effect of the endoscopic duodenal-jejunal bypass liner on obesity and type 2
      diabetes mellitus, a multicenter randomized controlled trial.
AB  - OBJECTIVE: Investigate the safety and efficacy of 6 months' duodenal-jejunal
      bypass liner (DJBL) treatment in comparison with dietary intervention for obesity
      and type 2 diabetes mellitus (T2DM). BACKGROUND: The DJBL is a bariatric
      procedure involving an impermeable sleeve that is delivered endoscopically in the
      proximal intestine. This procedure not only is less invasive than conventional
      surgical techniques but also has beneficial effects on obesity and T2DM. METHODS:
      A multicenter randomized controlled trial was conducted. Seventy-seven patients
      with obesity and T2DM were included. Thirty-eight patients were randomized to 6
      months' DJBL treatment in combination with dietary intervention (34 successfully
      implanted, 31 completed the study), 39 patients received only dietary
      intervention (controls, 35 completed the study). Total study duration for both
      groups was 12 months, including 6 months of post-DJBL removal follow-up. RESULTS:
      After 6 months, just before DJBL removal, the DJBL group had lost 32.0% [22.0%
      46.7%] of their excess weight versus 16.4% [4.1%-34.6%] in the control group (P <
      0.05). Glycated hemoglobin A1c levels improved to 7.0% [6.4%-7.5%] in the DJBL
      group and to 7.9% [6.6%-8.3%] in the control group (P < 0.05). In addition, 85.3%
      of DJBL patients showed decreased postprandial glucose excursions versus 48.7% of
      control patients (P < 0.05). At 12 months, excess weight loss of the DJBL group
      was 19.8% [10.6%-45.0%] versus 11.7% [1.4%-25.4%] in the control group (P <
      0.05). HbA1c was 7.3% [6.6%-8.0%] versus 8.0% [6.8%-8.8%], DJBL versus control
      respectively (P = ns). CONCLUSIONS: The DJBL is a safe and effective alternative
      to invasive bariatric procedures. Six months of DJBL treatment combined with diet
      leads to superior weight loss and improvement of T2DM when compared with diet
      alone.

PMID- 25072437
TI  - A comparison of the surgical outcomes among patients with HBV-positive, HCV
      positive, and non-B non-C hepatocellular carcinoma: a nationwide study of 11,950
      patients.
AB  - OBJECTIVE: To compare the prognostic factors and outcomes after hepatic resection
      among patients with hepatitis B virus (HBV)-positive, hepatitis C virus (HCV)
      positive, and negative for hepatitis B surface antigen and hepatitis C antibody,
      so-called "NBNC"-hepatocellular carcinoma (HCC) using the data from a nationwide
      survey. BACKGROUND: The incidence of NBNC-HCC is rapidly increasing in Japan.
      METHODS: A total of 11,950 patients with HBV-HCC (n = 2194), HCV-HCC (n = 7018),
      or NBNC-HCC (n = 2738) who underwent a curative hepatic resection were enrolled
      in this study. The clinicopathological features were compared among the groups.
      The significant prognostic variables determined by univariate analysis were
      subjected to a multivariate analysis using a Cox proportional hazard regression
      model. RESULTS: Liver function in the HCV-HCC group was significantly worse than
      that in the HBV-HCC and NBNC-HCC groups. The NBNC-HCC group had significantly
      more advanced HCC than the HCV-HCC group. The 5-year overall survival rates after
      hepatectomy in the HBV-HCC, HCV-HCC, and NBNC-HCC groups were 65%, 59%, and 68%,
      respectively. The 5-year recurrence-free survival (RFS) rates in these 3 groups
      were 41%, 31%, and 47%, respectively. Stratifying the RFS rates according to the
      TNM stage showed that the NBNC-HCC group had a significantly better prognosis
      than the HBV-HCC group in stages II, III, and IVA, and a significantly better
      prognosis than the HCV-HCC group in stages I and II. Multivariate analysis
      revealed a significantly better RFS rate in the NBNC-HCC group. CONCLUSIONS: The
      findings of this nationwide survey indicated that patients with NBNC-HCC had a
      significantly lower risk of HCC recurrence than those with HBV-HCC and HCV-HCC.

PMID- 25072438
TI  - Modified complete mesocolic excision with central vascular ligation for the
      treatment of right-sided colon cancer: long-term outcomes and prognostic factors.
AB  - OBJECTIVE: To investigate the long-term oncologic outcomes and risk factors for
      adverse effects in right-sided colon cancer patients who underwent modified
      complete mesocolic excision (mCME). BACKGROUND: Complete mesocolic excision (CME)
      with central vascular ligation has recently been found to improve oncological
      outcomes in patients with colon cancer. Our institution has established mCME on
      the basis of the original concept of CME for the treatment of right-sided colon
      cancer. METHODS: Between January 2000 and July 2009, 773 patients who underwent
      mCME for right-sided colon cancer were eligible for this retrospective study. The
      prognostic factors for survival/recurrence and the risk factors for postoperative
      complications were investigated. RESULTS: The mean follow-up period was 61.9 +/-
      34.7 months. The 5-year overall survival and 5-year disease-free survival rates
      were 84.0% and 82.8%, respectively. Pathologic stage III disease, postoperative
      complications, age more than 60 years, and minimally invasive surgery were found
      to be independent prognostic factors. The 5-year locoregional recurrence (LRR)
      and 5-year systemic recurrence rates (SRRs) were 4.9% and 13.7%, respectively.
      The risk of LRR and SRR increased with pathologic stage III disease. An American
      Society of Anesthesiology score of higher than II was an independent predictive
      factor of postoperative complications. CONCLUSIONS: We have successfully
      established the mCME technique, on the basis of the same principle as CME, but
      with a more tailored approach. The long-term oncologic outcomes and risk of
      postoperative morbidity were found to be comparable with those seen with the
      original CME procedure.

PMID- 25072439
TI  - Did Peritoneal Metastases From Colorectal Cancers Experience Similar Survival
      With Resected Liver Metastases?

PMID- 25072440
TI  - The Use of Caffeinated Substances by Surgeons for Cognitive Enhancement.
AB  - OBJECTIVE: To investigate the use of coffee, caffeinated drinks, and caffeine
      tablets for pharmacological cognitive enhancement (CE) among surgeons.
      BACKGROUND: Surgeons have demanding workloads, and the resulting fatigue and
      concentration deficits can lead to medical errors. Some surgeons use substances
      that promote wakefulness to counteract these effects. METHODS: A total of 3306
      surgeons who attended 5 international conferences in 2011 were surveyed regarding
      their use of coffee, caffeinated drinks, and caffeine tablets for CE and
      potential factors derived from professional and private life using an anonymous
      self-report questionnaire. In this study, we were only interested in surgeons
      working in hospitals; therefore, 951 questionnaires were statistically analyzed.
      RESULTS: The most prevalent reason for using caffeine of any kind was to reduce
      fatigue (54.3%). Further prevalent reasons are working the night shift (32.2%)
      and overly long and excessive work hours (31.7%). Lifetime, past-year, past
      month, and past-week prevalence was 66.8%, 61.9%, 56.9%, and 50.5%, for coffee
      use; 24.2%, 15.4%, 9.9%, and 6.1%, for caffeinated drinks; and 12.6%, 5.9%, 4.7%,
      and 3.8%, respectively, for caffeine tablets. Caffeine use was associated with
      lower age, male sex, divorced marital status, living with children, lack of
      satisfaction with professional status, pressure to perform in private life, and
      pressure perceived to be harmful to one's own health. CONCLUSIONS: Surgeons often
      use caffeinated substances to cope with fatigue and long working hours. Coffee
      use was more prevalent than the use of caffeinated drinks and caffeine tablets.

PMID- 25072441
TI  - Nonoperative treatment with antibiotics versus surgery for acute nonperforated
      appendicitis in children: a pilot randomized controlled trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility and safety of
      nonoperative treatment of acute nonperforated appendicitis with antibiotics in
      children. METHODS: A pilot randomized controlled trial was performed comparing
      nonoperative treatment with antibiotics versus surgery for acute appendicitis in
      children. Patients with imaging-confirmed acute nonperforated appendicitis who
      would normally have had emergency appendectomy were randomized either to
      treatment with antibiotics or to surgery. Follow-up was for 1 year. RESULTS:
      Fifty patients were enrolled; 26 were randomized to surgery and 24 to
      nonoperative treatment with antibiotics. All children in the surgery group had
      histopathologically confirmed acute appendicitis, and there were no significant
      complications in this group. Two of 24 patients in the nonoperative treatment
      group had appendectomy within the time of primary antibiotic treatment and 1
      patient after 9 months for recurrent acute appendicitis. Another 6 patients have
      had an appendectomy due to recurrent abdominal pain (n = 5) or parental wish (n =
      1) during the follow-up period; none of these 6 patients had evidence of
      appendicitis on histopathological examination. CONCLUSIONS: Twenty-two of 24
      patients (92%) treated with antibiotics had initial resolution of symptoms. Of
      these 22, only 1 patient (5%) had recurrence of acute appendicitis during follow
      up. Overall, 62% of patients have not had an appendectomy during the follow-up
      period. This pilot trial suggests that nonoperative treatment of acute
      appendicitis in children is feasible and safe and that further investigation of
      nonoperative treatment is warranted.

PMID- 25072442
TI  - The influence of volume and experience on individual surgical performance: a
      systematic review.
AB  - OBJECTIVE: To systematically review studies evaluating the influence of surgical
      experience on individual performance. BACKGROUND: Experience, measured in case
      volume or years of practice, is recognized as a key driver of individual surgical
      performance, giving rise to a learning curve. However, this topic has not been
      reviewed at the cross-specialty level. METHODS: MEDLINE, EMBASE, PsycINFO, AMED,
      and the Cochrane Database of Systematic Reviews were searched (from inception to
      February 2013). Two reviewers independently reviewed citations using
      predetermined inclusion and exclusion criteria. Ninety-one data points per study
      were extracted. RESULTS: The search strategy yielded 6950 citations. Fifty-seven
      studies were eligible, including 1,061,913 cases and 35 procedure types,
      performed by 17,912 surgeons. Forty-five studies monitored case volume, and 6
      studies measured experience as both case volume and years of practice. Of these
      51 studies, 44 found that increased case volume was associated with significantly
      improved health outcomes. Several studies noted a plateau phase or maturation in
      the surgical learning curve. Acquisition of this phase was procedure specific and
      outcome specific, ranging from 25 to 750 procedures. Twelve studies assessed the
      impact of years of surgical practice, 11 of which found that increased years of
      experience was associated with significantly improved health outcomes. Two
      studies noted a plateau phase, where increases in years of experience were no
      longer associated with improvements in operative outcomes. Three studies
      identified performance deterioration after the plateau phase. CONCLUSIONS:
      Increasing surgical case volume and years of practice are associated with
      improved performance, in a procedure-specific manner. Performance may deteriorate
      toward the end of a surgeon's career.

PMID- 25072443
TI  - Detailed description of all deaths in both the shock and traumatic brain injury
      hypertonic saline trials of the Resuscitation Outcomes Consortium.
AB  - OBJECTIVE: To identify causes and timing of mortality in trauma patients to
      determine targets for future studies. BACKGROUND: In trials conducted by the
      Resuscitation Outcomes Consortium in patients with traumatic hypovolemic shock
      (shock) or traumatic brain injury (TBI), hypertonic saline failed to improve
      survival. Selecting appropriate candidates is challenging. METHODS: Retrospective
      review of patients enrolled in multicenter, randomized trials performed from 2006
      to 2009. Inclusion criteria were as follows: injured patients, age 15 years or
      more with hypovolemic shock [systolic blood pressure (SBP) <= 70 mm Hg or SBP 71
      90 mm Hg with heart rate >= 108) or severe TBI [Glasgow Coma Score (GCS) <= 8].
      Initial fluid administered was 250 mL of either 7.5% saline with 6% dextran 70,
      7.5% saline or 0.9% saline. RESULTS: A total of 2061 subjects were enrolled (809
      shock, 1252 TBI) and 571 (27.7%) died. Survivors were younger than nonsurvivors
      [30 (interquartile range 23) vs 42 (34)] and had a higher GCS, though similar
      hemodynamics. Most deaths occurred despite ongoing resuscitation. Forty-six
      percent of deaths in the TBI cohort were within 24 hours, compared with 82% in
      the shock cohort and 72% in the cohort with both shock and TBI. Median time to
      death was 29 hours in the TBI cohort, 2 hours in the shock cohort, and 4 hours in
      patients with both. Sepsis and multiple organ dysfunction accounted for 2% of
      deaths. CONCLUSIONS: Most deaths from trauma with shock or TBI occur within 24
      hours from hypovolemic shock or TBI. Novel resuscitation strategies should focus
      on early deaths, though prevention may have a greater impact.

PMID- 25072444
TI  - Antiviral therapy improves postoperative survival in patients with hepatocellular
      carcinoma: a randomized controlled trial.
AB  - OBJECTIVE: A randomized controlled trial was conducted to find out whether
      antiviral therapy in patients with hepatitis B-related hepatocellular carcinoma
      (HCC) improves long-term survival after hepatic resection. BACKGROUND: Despite
      advances in surgery and in multidisciplinary treatment, there is still no
      effective adjuvant treatment to prevent HCC recurrence after R0 resection for
      HCC. Whether antiviral therapy is useful in reducing postoperative HCC recurrence
      is unclear. METHODS: Between May 2007 and April 2008, patients who received R0
      hepatic resection for HBV-related HCC were randomly assigned to receive no
      treatment (the control group, n = 100) or antiviral therapy (adefovir 10 mg/d,
      the antiviral group, n = 100). RESULTS: The baseline clinical, laboratory, and
      tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year
      recurrence-free survival rates for the antiviral group and the control group were
      85.0%, 50.3%, 46.1% and 84.0%, 37.9%, 27.1%, respectively. The corresponding
      overall survival rates for the 2 groups were 96.0%, 77.6%, 63.1% and 94.0%,
      67.4%, 41.5%, respectively. The recurrence-free survival and overall survival for
      the antiviral group were significantly better than the control group (P = 0.026,
      P = 0.001). After adjusting for the confounding prognostic factors in a Cox
      model, the relative risks of recurrence and death for antiviral treatment were
      0.651 [95% confidence interval (CI): 0.451-0.938; P = 0.021] and 0.420 (95% CI:
      0.271-0.651; P < 0.001). Antiviral therapy was an independent protective factor
      of late tumor recurrence (HR = 0.348, 95% CI: 0.177-0.687; P = 0.002) but not of
      early tumor recurrence [hazard ratio (HR) = 0.949, 95% CI: 0.617-1.459; P =
      0.810]. CONCLUSIONS: In patients with hepatitis B-related HCC, adefovir antiviral
      therapy reduced late HCC recurrence and significantly improved overall survival
      after R0 hepatic resection.

PMID- 25072445
TI  - Avoid "All-Touch" by Hybrid ALPPS to Achieve Oncological Efficacy.

PMID- 25072446
TI  - Standardization of laparoscopic total mesorectal excision for rectal cancer: a
      structured international expert consensus.
AB  - OBJECTIVE: To establish a structured international expert consensus on a detailed
      technical description of the laparoscopic total mesorectal excision (TME).
      BACKGROUND: Laparoscopic TME is a common surgical approach for the treatment of
      rectal cancer, but there is little agreement on technical details and standards.
      METHODS: Sixty leading surgical experts from 5 different world regions with a
      median overall experience of 250 laparoscopic TME participated in this study.
      Four stages of mixed quantitative and qualitative consensus-finding methods were
      applied. (1) Semistructured expert interviews were independently analyzed by 2
      assessors. (2) Consensus on the interview data was reached using reiterating
      questionnaires (Delphi method). (3) This was further refined in an interactive
      workshop. (4) Based on this meeting, a comprehensive text was drafted and final
      approval was sought by all experts. FINDINGS: Three theme categories were
      identified in 9 detailed interviews (anatomical landmarks, description of tissue
      retraction, and operating strategies). Following 2 rounds of a 54-item
      questionnaire, 29 items achieved very high agreement (A* >=90%), 14 with good
      agreement (>=80%), 13 with moderate agreement (>=50%), and 18 with little or no
      agreement (<50%). In the workshop, areas of agreement were consolidated and
      conclusions were sought for those with less agreement. The final document was
      approved after 2 further rounds of surveys by all respondents. CONCLUSIONS: This
      detailed and agreed technical description of laparoscopic TME may have
      implications on training, assessment, quality control, and future research.

PMID- 25072447
TI  - Reply to Letter: "Surgical Ward Round Quality and Impact on Variable Patient
      Outcomes".

PMID- 25072448
TI  - Reply to Letter: "Inconsistent Data Resources Weaken the Quality of Research
      Results".

PMID- 25072449
TI  - PREOP-Gallstones: A Prognostic Nomogram for the Management of Symptomatic
      Cholelithiasis in Older Patients.
AB  - OBJECTIVE AND BACKGROUND: The decision regarding elective cholecystectomy in
      older patients with symptomatic cholelithiasis is complicated. We developed and
      validated a prognostic nomogram to guide shared decision making for these
      patients. METHODS: We used Medicare claims (1996-2005) to identify the first
      episode of symptomatic cholelithiasis in patients older than 65 years who did not
      undergo hospitalization or elective cholecystectomy within 2.5 months of the
      episode. We described current patterns of care and modeled their risk of emergent
      gallstone-related hospitalization or cholecystectomy at 2 years. Model
      discrimination and calibration were assessed using a random split sample of
      patients. RESULTS: We identified 92,436 patients who presented to the emergency
      department (8.3%) or physician's office (91.7%) and who were not immediately
      admitted. The diagnosis for the initial episode was biliary colic/dyskinesia
      (65.3%), acute cholecystitis (26.6%), choledocholithiasis (5.7%), or gallstone
      pancreatitis (2.4%). The 2-year emergent gallstone-related hospitalization rate
      was 11.1%, with associated in-hospital morbidity and mortality rates of 56.5% and
      6.5%. Factors associated with gallstone-related acute hospitalization included
      male sex, increased age, fewer comorbid conditions, complicated biliary disease
      on initial presentation, and initial presentation to the emergency department.
      Our model was well calibrated and identified 51% of patients with a risk less
      than 10% for 2-year complications and 5.4% with a risk more than 40% (C
      statistic, 0.69; 95% confidence interval, 0.63-0.75). CONCLUSIONS: Surgeons can
      use this prognostic nomogram to accurately provide patients with their 2-year
      risk of developing gallstone-related complications, allowing patients and
      physicians to make informed decisions in the context of their symptom severity
      and its impact on their quality of life.

PMID- 25072450
TI  - The medical education partnership initiative--moving from mumbo jumbo to real
      understanding.

PMID- 25072451
TI  - Gender-based salary disparities: it pays to take a closer look.

PMID- 25072452
TI  - In reply to Ambati.

PMID- 25072453
TI  - Can increasing minority faculty lead to increasing the workforce for underserved
      and minority populations?

PMID- 25072454
TI  - In reply to Campbell and Rodriguez.

PMID- 25072455
TI  - Market failure in medical education.

PMID- 25072456
TI  - In reply to Walsh.

PMID- 25072457
TI  - Back to bayesics.

PMID- 25072458
TI  - "Tova": it means good.

PMID- 25072462
TI  - Medicine and the arts. Pirkei Avot (ethics of the fathers) [excerpt] by Hyman E.
      Goldin. Commentary.

PMID- 25072460
TI  - The lottery tickets.

PMID- 25072463
TI  - Reality check: a reflection on refugee health.

PMID- 25072464
TI  - Low-density three-dimensional foam using self-reinforced hybrid two-dimensional
      atomic layers.
AB  - Low-density nanostructured foams are often limited in applications due to their
      low mechanical and thermal stabilities. Here we report an approach of building
      the structural units of three-dimensional (3D) foams using hybrid two-dimensional
      (2D) atomic layers made of stacked graphene oxide layers reinforced with
      conformal hexagonal boron nitride (h-BN) platelets. The ultra-low density (1/400
      times density of graphite) 3D porous structures are scalably synthesized using
      solution processing method. A layered 3D foam structure forms due to presence of
      h-BN and significant improvements in the mechanical properties are observed for
      the hybrid foam structures, over a range of temperatures, compared with pristine
      graphene oxide or reduced graphene oxide foams. It is found that domains of h-BN
      layers on the graphene oxide framework help to reinforce the 2D structural units,
      providing the observed improvement in mechanical integrity of the 3D foam
      structure. 

PMID- 25072465
TI  - Specific learning disorder: prevalence and gender differences.
AB  - Comprehensive models of learning disorders have to consider both isolated
      learning disorders that affect one learning domain only, as well as comorbidity
      between learning disorders. However, empirical evidence on comorbidity rates
      including all three learning disorders as defined by DSM-5 (deficits in reading,
      writing, and mathematics) is scarce. The current study assessed prevalence rates
      and gender ratios for isolated as well as comorbid learning disorders in a
      representative sample of 1633 German speaking children in 3rd and 4th Grade.
      Prevalence rates were analysed for isolated as well as combined learning
      disorders and for different deficit criteria, including a criterion for normal
      performance. Comorbid learning disorders occurred as frequently as isolated
      learning disorders, even when stricter cutoff criteria were applied. The relative
      proportion of isolated and combined disorders did not change when including a
      criterion for normal performance. Reading and spelling deficits differed with
      respect to their association with arithmetic problems: Deficits in arithmetic co
      occurred more often with deficits in spelling than with deficits in reading. In
      addition, comorbidity rates for arithmetic and reading decreased when applying
      stricter deficit criteria, but stayed high for arithmetic and spelling
      irrespective of the chosen deficit criterion. These findings suggest that the
      processes underlying the relationship between arithmetic and reading might differ
      from those underlying the relationship between arithmetic and spelling. With
      respect to gender ratios, more boys than girls showed spelling deficits, while
      more girls were impaired in arithmetic. No gender differences were observed for
      isolated reading problems and for the combination of all three learning
      disorders. Implications of these findings for assessment and intervention of
      learning disorders are discussed. 

PMID- 25072466
TI  - Physicians' attitudes and use of e-cigarettes as cessation devices, North
      Carolina, 2013.
AB  - INTRODUCTION: Electronic cigarettes (e-cigarettes) are not currently approved or
      recommended by the Food and Drug Administration (FDA) or various medical
      organizations; yet, they appear to play a substantial role in tobacco users'
      cessation attempts. This study reports on a physician survey that measured
      beliefs, attitudes, and behavior related to e-cigarettes and smoking cessation.
      To our knowledge this is the first study to measure attitudes toward e-cigarettes
      among physicians treating adult smokers. METHODS: Using a direct marketing
      company, a random sample of 787 North Carolina physicians were contacted in 2013
      through email, with 413 opening the email and 128 responding (response rate =
      31%). Physicians' attitudes towards e-cigarettes were measured through a series
      of close-ended questions. Recommending e-cigarettes to patients served as the
      outcome variable for a logistic regression analysis. RESULTS: Two thirds (67%) of
      the surveyed physicians indicated e-cigarettes are a helpful aid for smoking
      cessation, and 35% recommended them to their patients. Physicians were more
      likely to recommend e-cigarettes when their patients asked about them or when the
      physician believed e-cigarettes were safer than smoking standard cigarettes.
      CONCLUSIONS: Many North Carolina physicians are having conversations about e
      cigarettes with their patients, and some are recommending them. Future FDA
      regulation of e-cigarettes may help provide evidence-based guidance to physicians
      about e-cigarettes and will help ensure that patients receive evidence-based
      recommendations about the safety and efficacy of e-cigarettes in tobacco
      cessation.

PMID- 25072468
TI  - A portable lipid bilayer system for environmental sensing with a transmembrane
      protein.
AB  - This paper describes a portable measurement system for current signals of an ion
      channel that is composed of a planar lipid bilayer. A stable and reproducible
      lipid bilayer is formed in outdoor environments by using a droplet contact method
      with a micropipette. Using this system, we demonstrated that the single-channel
      recording of a transmembrane protein (alpha-hemolysin) was achieved in the field
      at a high-altitude (~3623 m). This system would be broadly applicable for
      obtaining environmental measurements using membrane proteins as a highly
      sensitive sensor. 

PMID- 25072467
TI  - New neotropical sebacinales species from a Pakaraimaea dipterocarpacea forest in
      the Guayana Region, Southern Venezuela: structural diversity and phylogeography.
AB  - Pakaraimaea dipterocarpacea, a member of the Dipterocarpaceae endemic in the
      Guayana region, is associated with a diverse community of ectomycorrhizal (ECM)
      fungi. Amongst the 41 ECM fungal species detected in a 400 m2 P. dipterocarpacea
      ssp. nitida plot in Southern Venezuela, three species belonged to the
      Sebacinales. We tested whether ECM anatomotype characterization can be used as a
      feasible element in an integrative taxonomy in this diverse fungal group, where
      the relevance of fruitbody morphology for species delimitation seems limited.
      Using a combination of ECM morpho-anatomical characterizations and phylogenetic
      analyses based on nuclear ITS and LSU sequences, we report three new species. The
      main distinguishing features of Sebacina guayanensis are the yellowish cell walls
      together with conspicuous undifferentiated, uniform compact (type B) rhizomorphs.
      Staghorn-like hyphae are characteristic of S. tomentosa. The combination of
      clusters of thick-walled emanating hyphae, including hyphae similar to awl-shaped
      cystidia with basal dichotomous or trichotomous ramifications, and the presence
      of type B rhizomorphs were characteristic of a third, yet unnamed species. The
      three species belong to three different, possibly specifically tropical clades in
      Sebacinales Group A. The geographic distribution of phylogenetically related
      strains was wide, including a Dicymbe forest in Guyana and an Ecuadorian
      rainforest with Coccoloba species. We show that ECM morpho-anatomy can be used,
      in combination with other analyses, to delineate species within Sebacinales Group
      A. In addition to phylogenetic information, type B rhizomorphs observed in
      different Sebacinales clades have important ecological implications for this
      fungal group. The phylogeography of Sebacinales suggests that dispersion and host
      jump are important radiation mechanisms that shaped P. dipterocarpacea ECM fungal
      community. This study emphasizes the need for more sequence data to evaluate the
      hypothesis that phylogeographic relationships between neo- and paleotropical ECM
      fungal species could be attributed to the vicariance of cross-continental hosts
      such as the Dipterocarpacae. 

PMID- 25072470
TI  - Electrochemical properties and relaxation times of the hematite/water interface.
AB  - Electric double layer properties and protonation rates at the surface of a
      mechanically and chemically polished (001) surface of hematite (alpha-Fe2O3)
      contacted with aqueous solutions of NaCl were extracted by electrochemical
      impedance spectroscopy (EIS). Effects of pH (4-12) and ionic strength (10-1000
      mM) on the EIS response of the electrode were predicted using an electrical
      equivalent circuit model accounting for hematite bulk and interfacial processes.
      These efforts generated diffuse layer as well as compact layer capacitances and
      resistance values pertaining to interfacial processes. Diffuse layer capacitance
      values lie in the 0.5-0.6 MUF cm(-2) region and are about 1.5 times smaller than
      those obtained on a roughened hematite surface. Compact layer capacitances are
      strongly pH dependent as they pertain to the transfer of ions (charge carriers)
      from the diffuse layer onto surface (hydr)oxo groups. These values, alongside
      those of resistance adsorption, pointed a 50% decrease in proton
      adsorption/desorption resistance under acidic and alkaline conditions relative to
      that of the point of zero charge (pH 8-9). Increasing ionic strength generally
      induces larger diffuse layer capacitances, larger adsorption capacitances, and
      lower resistance values. Such a response is in line with the concept for thinner
      electric double layers and facilitated proton adsorption reactions by solutions
      of high ionic strengths. Relaxation times pertaining to the transfer of charge
      carriers across the compact plane induced by the EIS experiments lie in the 0.7
      4.2 s range and become larger under acidic conditions. Decreases in site
      availability and increases in electrostatic repulsion are two possible
      contributing factors impeding reaction rates below the point of zero charge.
      Collectively, these finding are underpinning important relationships between
      classical views on mineral surface complexation reactions and electrochemical
      views of semiconductor/water interfaces. 

PMID- 25072471
TI  - Functionally diverse dendritic mRNAs rapidly associate with ribosomes following a
      novel experience.
AB  - The subcellular localization and translation of messenger RNA (mRNA) supports
      functional differentiation between cellular compartments. In neuronal dendrites,
      local translation of mRNA provides a rapid and specific mechanism for synaptic
      plasticity and memory formation, and might be involved in the pathophysiology of
      certain brain disorders. Despite the importance of dendritic mRNA translation,
      little is known about which mRNAs can be translated in dendrites in vivo and when
      their translation occurs. Here we collect ribosome-bound mRNA from the dendrites
      of CA1 pyramidal neurons in the adult mouse hippocampus. We find that dendritic
      mRNA rapidly associates with ribosomes following a novel experience consisting of
      a contextual fear conditioning trial. High throughput RNA sequencing followed by
      machine learning classification reveals an unexpected breadth of ribosome-bound
      dendritic mRNAs, including mRNAs expected to be entirely somatic. Our findings
      are in agreement with a mechanism of synaptic plasticity that engages the acute
      local translation of functionally diverse dendritic mRNAs. 

PMID- 25072472
TI  - Periodic changes in the distribution of species observed in the Ni(2+)-histidine
      equilibrium coupled to the BrO3(-)-SO3(2-) pH oscillator.
AB  - The dynamical behavior of the system comprising of the pH-dependent complex
      formation between histidine and Ni(II) ions coupled to the BrO3(-)-SO3(2-) pH
      oscillator was studied. The pH oscillator was demonstrated to be capable of
      forcing the pH-sensitive nickel ion-histidine equilibrium to alternate
      periodically between the unreacted and the fully complexed states. The periodic
      interconversions gave rise to an oscillatory distribution of the species that
      participate in the equilibrium and resulted in oscillations in the free [Ni(2+)],
      [NiHis(+)], and [Ni(His)2]. The preconditions of the successful coupling of metal
      ion-amino acid complexes to a primary pH oscillator are briefly discussed. Model
      calculations were performed to simulate the dynamics observed in the BrO3(-)
      SO3(2-) - Ni(2+)-His CSTR system. 

PMID- 25072473
TI  - Evidence of eelgrass (Zostera marina) seed dispersal by northern diamondback
      terrapin (Malaclemys terrapin terrapin) in lower Chesapeake Bay.
AB  - The initial discovery in May 2009 of eelgrass (Zostera marina) seeds in fecal
      samples of wild-caught northern diamondback terrapins (Malaclemys terrapin
      terrapin) was the first field evidence of eelgrass seed ingestion in this
      species. This finding suggested the potential of terrapins as seed dispersers in
      eelgrass beds, which we sampled for two additional years (2010 and 2011). Seeds
      were only found in feces of terrapins captured prior to June 8 in all three
      years, coinciding with eelgrass seed maturation and release. Numbers of seeds in
      terrapin feces varied annually and decreased greatly in 2011 after an eelgrass
      die off in late 2010. The condition of seeds in terrapin feces was viable-mature,
      germinated, damaged, or immature. Of terrapins captured during time of seed
      release, 97% were males and juvenile females, both of which had head widths <30
      mm. The fraction of individuals with ingested seeds was 33% for males, 35% for
      small females, and only 6% for large (mature) females. Probability of seed
      ingestion decreased exponentially with increasing terrapin head width; only males
      and small females (head width <30 mm) were likely to be vectors of seed
      dispersal. The characteristic that diamondback terrapins have well-defined home
      ranges allowed us to estimate the number of terrapins potentially dispersing
      eelgrass seeds annually. In seagrass beds of the Goodwin Islands region (lower
      York River, Virginia), there were 559 to 799 terrapins, which could disperse
      between 1,341 and 1,677 eelgrass seeds annually. These would represent a small
      proportion of total seed production within a single seagrass bed. However, based
      on probable home range distances, terrapins can easily traverse eelgrass meadow
      boundaries, thereby dispersing seeds beyond the bed of origin. Given the
      relatively short dispersion distance of eelgrass seeds, the diamondback terrapin
      may be a major source of inter-bed seed dispersal and genetic diversity. 

PMID- 25072474
TI  - Pulmonary deadspace and postoperative outcomes in neonates undergoing stage 1
      palliation operation for single ventricle heart disease.
AB  - OBJECTIVES: Increased pulmonary dead space fraction (VD/VT) has been associated
      with prolonged mechanical ventilation after surgery for congenital heart disease.
      The association of VD/VT with clinical outcomes in neonates undergoing stage 1
      palliation for single ventricle congenital heart disease has not been reported.
      We describe changes in VD/VT, differences in VD/VT based on shunt type (right
      ventricle to pulmonary artery conduit vs modified Blalock-Taussing shunt) and
      association of VD/VT with postoperative outcomes in patients undergoing stage 1
      palliation. DESIGN: Retrospective chart review for demographic, hemodynamics,
      outcome information, and VD/VT values were collected at 6-hour intervals during
      the first 48 postoperative hours in neonates undergoing stage 1 palliation. VD/VT
      was calculated using mixed expired CO2 (PeCO2) obtained from capnography and
      paired arterial blood gas CO2 values. SETTING: Cardiac ICU in a tertiary care
      pediatric hospital. PATIENTS: Newborns with single ventricle congenital heart
      disease undergoing stage 1 palliation during 2003-2004. MEASUREMENTS AND MAIN
      RESULTS: Of the 51 patients, 31 had right ventricle to pulmonary artery and 20
      had Blalock-Taussing shunt. Although VD/VT was lower in the Blalock-Taussing
      shunt group over all time points (p = 0.02), maximal VD/VT on day 1 (0.49 +/-
      0.07) and on day 2 (0.46 +/- 0.08) were not different between the shunt groups.
      VD/VT decreased significantly over time in both shunt groups (p = 0.001 for right
      ventricle to pulmonary artery; p < 0.001 for Blalock-Taussing shunt). Higher
      maximal VD/VT during first 48 postoperative hours was independently associated
      with fewer ventilator (beta = -26.6; p = 0.035) and hospital-free days in the
      first month after stage 1 palliation (beta = -40.4; p = 0.002) after adjusting
      for potential confounders in a multivariable linear regression model.
      CONCLUSIONS: Increased pulmonary dead space exists early after stage 1 palliation
      operation for single ventricle congenital heart disease. Higher VD/VT during the
      first 48 postoperative hours was associated with longer duration of ventilation
      and hospital LOS and may be a useful marker of postoperative outcomes in this
      population.

PMID- 25072475
TI  - Transcranial Doppler-based assessment of cerebral autoregulation in critically
      ill children during diabetic ketoacidosis treatment.
AB  - OBJECTIVES: Impaired cerebral autoregulation may be associated with poor outcome
      in diabetic ketoacidosis. We examined change in cerebral autoregulation during
      diabetic ketoacidosis treatment. DESIGN: Prospective observational cohort study.
      SETTING: Tertiary care children's hospital. PATIENTS/SUBJECTS: Children admitted
      to the ICU with diabetic ketoacidosis (venous pH < 7.3, glucose > 300 mg/dL, HCO3
      < 15 mEq/L, and ketonuria) constituted cases, and children with type I diabetes
      without diabetic ketoacidosis constituted controls. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Between 2005 and 2009, 32 cases and 50 controls
      were enrolled. Transcranial Doppler ultrasonography was used to measure middle
      cerebral artery flow velocities, and cerebral autoregulation testing was achieved
      via tilt-table testing. Cases underwent two and controls underwent one cerebral
      autoregulation test. Cerebral autoregulation was quantified by the autoregulatory
      index (autoregulatory index < 0.4 = impaired and autoregulatory index 0.4-1.0 =
      intact autoregulation). The first autoregulation test was obtained early (time 1,
      12-24 hr; median [interquartile range], 8 hr [5-18 hr]) during diabetic
      ketoacidosis treatment, and a second autoregulation test was obtained during
      recovery (time 2, 36-72 hr; median [ interquartile range], 46 hr [40-59 hr]) from
      time 0 (defined as time of insulin start). Cases had lower autoregulatory index
      at time 1 than time 2 (p < 0.001) as well lower autoregulatory index than control
      subjects (p < 0.001). Cerebral autoregulation was impaired in 40% (n = 13) of
      cases at time 1 and in 6% (n = 2) of cases at time 2. Five cases (17%) showed
      persistent impairment of cerebral autoregulation between times 1 and 2 of
      treatment. All control subjects had intact cerebral autoregulation. CONCLUSIONS:
      Impaired cerebral autoregulation was common early during diabetic ketoacidosis
      treatment. Although the majority improved during diabetic ketoacidosis treatment,
      17% of subjects had impairment between 36 and 72 hours after start of insulin
      therapy. The observed impaired cerebral autoregulation appears specific to the
      diabetic ketoacidosis process in patients with type I diabetes.

PMID- 25072476
TI  - Fatalities above 30,000 feet: characterizing pediatric deaths on commercial
      airline flights worldwide.
AB  - OBJECTIVES: We conducted this study to characterize in-flight pediatric
      fatalities onboard commercial airline flights worldwide and identify patterns
      that would have been unnoticed through single case analysis of these relative
      rare events. DESIGN: Retrospective cohort study of pediatric in-flight medical
      emergencies resulting in fatalities between January 2010 and June 2013. SETTING:
      A ground-based medical support center providing remote medical support to
      commercial airlines worldwide. PATIENTS: Children (age 0-18 yr) who experienced a
      medical emergency resulting in death during a commercial airline flight.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 7,573
      in-flight medical emergencies involving children reported to the ground-based
      medical support center, resulting in 10 deaths (0.13% of all pediatric in-flight
      emergencies). The median subject age was 3.5 months with 90% being younger than 2
      years, the age until which children are allowed to travel sharing a seat with an
      adult passenger, also known as lap infants. Six patients had no previous medical
      history, with one suffering cardiorespiratory arrest after developing acute
      respiratory distress during flight and five found asystolic (including four lap
      infants). Four subjects had preflight medical conditions, including two children
      traveling for the purpose of accessing advanced medical care. CONCLUSIONS:
      Pediatric in-flight fatalities are rare, but death occurs most commonly in
      infants and in subjects with a preexisting medical condition. The number of
      fatalities involving seemingly previously healthy children under the age of 2
      years (lap infants) is intriguing and could indicate a vulnerable population at
      increased risk of death related to in-flight environmental factors, sleeping
      arrangements, or yet another unrecognized factor.

PMID- 25072478
TI  - Risk factors for acquiring functional and cognitive disabilities during admission
      to a PICU*.
AB  - OBJECTIVE: To describe the risk factors for acquiring functional or cognitive
      disabilities during admission to a PICU. DESIGN: Retrospective analysis of a
      multicenter PICU database. SETTING: Twenty-four PICUs in the Virtual PICU
      Performance System network from January 1, 2009, through December 31, 2010.
      PATIENTS: Consecutive patients, who are 1 month to 18 years old, who survived to
      discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes
      were acquired global functional disability and cognitive disability during
      admission to a PICU, measured by change in Pediatric Overall Performance Category
      or in Pediatric Cerebral Performance Category scores, respectively. The primary
      analysis cohort consisted of 29,352 admissions to the 24 Virtual PICU Performance
      System sites which collected the main outcome variables. Respectively, 10.3% and
      3.4% of the cohort acquired global functional or cognitive disability. Trauma
      diagnosis (odds ratio, 4.50; 95% CI, 3.83-5.29; odds ratio, 3.91; 95% CI, 3.07
      4.98), unscheduled admission to the PICU (odds ratio, 2.67; 95% CI, 2.27-3.12;
      odds ratio, 1.52; 95% CI, 1.16-2.00), highest risk of mortality category (odds
      ratio, 1.19; 95% CI, 1.02-1.39; odds ratio, 2.70; 95% CI, 2.15-3.40), oncologic
      primary diagnoses (odds ratio, 5.61; 95% CI, 4.56-6.91; odds ratio, 4.30; 95% CI,
      2.97-6.24), and neurologic primary diagnoses (odds ratio, 2.04, 95% CI, 1.70
      2.44; odds ratio, 4.29, 95% CI, 3.18-5.78) were independently associated with
      acquiring both functional and cognitive disability. Intervention risk factors for
      acquiring both functional and cognitive disability included invasive mechanical
      ventilation (odds ratio, 1.79; 95% CI, 1.60-2.00; odds ratio, 2.83; 95% CI, 2.36
      3.39), renal replacement therapy (odds ratio, 2.43; 95% CI, 1.73-3.42; odds
      ratio, 1.76, 95% CI, 1.08-2.85), cardiopulmonary resuscitation (odds ratio, 1.91;
      95% CI, 1.24-2.95; odds ratio, 1.81; 95% CI, 1.02-3.23), and extracorporeal
      membrane oxygenation (odds ratio, 7.40, 95% CI, 4.10-13.36; odds ratio, 14.04,
      95% CI, 7.51-26.26). CONCLUSIONS: We identified a subset of patients whose
      potential for acquiring global functional and cognitive disability during
      admission to the PICU is high. This population may benefit from interventions
      that could mitigate this risk and from focused follow-up after discharge from the
      PICU.

PMID- 25072477
TI  - Comparative effectiveness of digoxin and propranolol for supraventricular
      tachycardia in infants.
AB  - OBJECTIVES: Supraventricular tachycardia is the most common arrhythmia in
      infants, and antiarrhythmic medications are frequently used for prophylaxis. The
      optimal prophylactic antiarrhythmic medication is unknown, and prior randomized
      trials have been underpowered. We used data from a large clinical registry to
      compare efficacy and safety of digoxin and propranolol for infant
      supraventricular tachycardia prophylaxis. We hypothesized that supraventricular
      tachycardia recurrence is less common on digoxin when compared with propranolol.
      DESIGN: Retrospective cohort study. SETTING: Pediatrix Medical Group neonatal
      ICUs. PATIENTS: Infants discharged from 1998 to 2012 with supraventricular
      tachycardia who were treated with digoxin or propranolol. We excluded infants
      discharged before completing 2 days of therapy, those with Wolff-Parkinson-White
      syndrome, structural heart defects (except atrial/ventricular septal defects and
      patent ductus arteriosus), and those started on multidrug therapy. MEASUREMENTS
      AND MAIN RESULTS: We used Cox proportional hazards to evaluate supraventricular
      tachycardia recurrence, defined as need for adenosine or electrical cardioversion
      while exposed to digoxin versus propranolol, controlling for infant
      characteristics, inotropic support, supplemental oxygen, and presence of a
      central line. We identified 342 infants exposed to digoxin and 142 infants
      exposed to propranolol. The incidence rate of treatment failure was 6.7/1,000
      infant-days of exposure to digoxin and 15.4/1,000 infant-days of exposure to
      propranolol. On multivariable analysis, treatment failure was higher on
      propranolol when compared with that on digoxin (hazard ratio, 1.97; 95% CI, 1.05
      3.71). Hypotension was more frequent during exposure to digoxin versus
      propranolol (39.4 vs 11.1/1,000 infant-days; p < 0.001). There was no difference
      in frequency of other clinical adverse events. CONCLUSIONS: Digoxin was
      associated with fewer episodes of supraventricular tachycardia recurrence but
      more frequent hypotension in hospitalized infants relative to propranolol.

PMID- 25072479
TI  - Training for public health preparedness--advancing the field.

PMID- 25072480
TI  - Evidence-based communications strategies: NWPERLC response to training on
      effectively reaching limited English-speaking (LEP) populations in emergencies.
AB  - INTRODUCTION: Identifying and overcoming barriers to effective emergency
      preparedness and response is one of the objectives for the Centers for Disease
      Control and Prevention's network of 14 Preparedness and Emergency Response
      Learning Centers (PERLCs) and 9 Preparedness and Response Research Centers
      (PERRCs). This report describes how a PERLC and a PERRC colocated at the
      Northwest Center for Public Health Practice responded to Los Angeles County
      Department of Public Health's (DPH's) request to improve emergency communications
      with limited English-proficient (LEP) populations. METHODS/ACTIVITY: Activities
      included an assessment of training needs of the DPH preparedness workforce, a
      training series on social media and community engagement, and a toolkit of
      evidence-based findings to improve LEP populations' emergency communications and
      community resilience. RESULTS/OUTCOMES: Most respondents to the training needs
      assessment considered themselves essential personnel during an emergency and
      stated that they have received proper training. Respondents would like to receive
      further emergency preparedness training, including additional clarity on their
      role during an emergency. The majority of participants rated the training series
      as excellent/very good and agreed that they will be able to apply the course
      content to their work. The percentage of participants who reported confidence in
      their knowledge and skills related to each course learning objective increased
      from the precourse survey to the postcourse survey. DISCUSSION: This article
      discusses how the colocation of PERRC and PERLC offers efficiencies and expertise
      to accomplish multicomponent evidence-based requests. The ability to translate
      research findings quickly into evidence-based training and best practice
      resources is a strategic benefit to public health practice agencies working on
      emergency preparedness. LESSONS LEARNED/NEXT STEPS: LA County DPH was able to use
      knowledge and lessons learned gained from this work to design and prioritize
      education and training offerings to improve the capacity to effectively engage
      and communicate with LEP communities before and during public health emergencies.

PMID- 25072481
TI  - The Southwest Preparedness and Emergency Response Learning Center and the
      Oklahoma inter tribal emergency management coalition: a unique partnership.
AB  - INTRODUCTION: Oklahoma is home to 39 Native American tribes, so the issue of
      tribal sovereignty had to be addressed before tribes, local, and state
      preparedness officials could work together successfully. We describe the unique
      partnership that was established when the Southwest Preparedness and Emergency
      Response Learning Center (SWPERLC) began working with tribes which led to the
      development of a tribal emergency management coalition. METHODS/ACTIVITY: The
      SWPERLC established a formal partnership with tribal emergency managers and a
      501(c)3 coalition was formed. The SWPERLC sponsors annual summits and attends
      and/or hosts monthly meetings, offering education and training opportunities year
      round. LESSONS LEARNED/NEXT STEPS: One example of a lesson learned resulted from
      a pandemic influenza survey administered to Oklahoma tribes. We learned that 40%
      of those Native Americans surveyed who chose not be vaccinated were concerned
      with side effects. Our evidence showed that improved public health conversations
      regarding the safety of vaccines must be had with the Native American community.
      RESULTS/OUTCOMES: Because of all the activities that were completed we now better
      understand how state and local preparedness officials can more successfully and
      beneficially work with tribes. Persistence, patience, and dedication were key
      factors highlighted during the formation of the coalition. Mutual respect and
      trust have allowed and will allow this partnership to continue.

PMID- 25072482
TI  - Community-Based Disaster Coalition training.
AB  - INTRODUCTION: One key activity of the University of South Florida Preparedness
      and Emergency Response Learning Center is designing, developing, and delivering
      community preparedness, response, and recovery system training.
      BACKGROUND/RATIONALE: Coalitions are vital for addressing emergencies or disaster
      situations within communities. The University of South Florida Community-Based
      Disaster Coalition was designed to address the challenges of building and
      sustaining coalitions, emphasize methods to enhance their sustainability and
      effectiveness, and strengthen their purpose and community impact during
      disasters. METHODS/ACTIVITY: Teams of participants were offered 2 years of
      training to support coalition-building efforts. In year 1, participants engaged
      in 3 days of facilitator-led instruction, hands-on activities, tabletop
      exercises, and breakout groups to learn techniques to strengthen their coalition,
      which are the focus of this study. In year 2, participants engaged in additional
      training through course refreshers, distance learning opportunities, and
      webinars. Participants were grouped by county or region and comprised 6 to 9
      people from a range of backgrounds and professions. RESULTS/OUTCOMES: During the
      2012 (year 1) trainings, 184 people attended the program, representing nearly
      half (31; 46%) of Florida counties. Performance data indicated that participants
      significantly improved their knowledge scores, and course evaluations indicated
      that they were satisfied with the course overall. DISCUSSION: The Community-Based
      Disaster Coalition trainings focused on community capacity of disaster response
      in 31 counties, which represents close to 13 million people or nearly three
      fourths of Florida residents. Training evaluations supported previous findings
      regarding critical coalition elements for development and sustainment, such as
      clear coalition purpose and goals. LESSONS LEARNED/NEXT STEPS: Several lessons
      were evident and inform future Community-Based Disaster Coalition efforts
      including adapting training to meet coalition needs; supporting the process of
      coalition building; following up with extended training opportunities and
      resources; continuing to provide trainings to counties that have not yet
      participated; and expanding training in other states, regions, territories, and
      internationally.

PMID- 25072483
TI  - Global health security: training a public health workforce to combat
      international and domestic threats.

PMID- 25072484
TI  - The Preparedness and Emergency Response Learning Centers: advancing standardized
      evaluation of public health preparedness and response trainings.
AB  - INTRODUCTION: The Centers for Disease Control and Prevention funded Preparedness
      and Emergency Response Learning Centers (PERLCs) across the United States. The
      PERLCs provide training to state, local, and tribal public health organizations
      to meet workforce development needs in the areas of public health preparedness
      and response, specialized training, education, and consultation.
      METHODS/ACTIVITY: Using Donald Kirkpatrick's training evaluation model, the PERLC
      network established 4 evaluation working groups that developed evaluation
      criteria to address each level of the model. The purpose of the working groups
      was to inform and promote center-level and program-level evaluation across the
      PERLC network; identify common training evaluation methods and measures; and
      share materials, resources, and lessons learned with state, local, and tribal
      public health organizations for potential replication. RESULTS/OUTCOMES: The
      evaluation of education and training, irrespective of its modality (eg, in
      person, online, webinars, seminars, symposia) can be accomplished using
      Kirkpatrick's 4-level taxonomy. DISCUSSION: The 4 levels aim to measure the
      following aspects of training programs: (1) trainees' reaction; (2) knowledge
      acquired, skills improved, or attitudes changed; (3) behavior changed; and (4)
      results or impact. To successfully evaluate emergency preparedness training,
      drills and exercises, it is necessary to understand the fundamental tenets of
      each level and how to apply each to measure training outcomes. LESSONS
      LEARNED/NEXT STEPS: The PERLC evaluators have adopted the basic schema of
      Kirkpatrick's 4-level model and applied its structure to a wide variety of
      preparedness and emergency response training and related activities. The PERLC
      evaluation working groups successfully developed and tested survey methods and
      instruments for each of the 4 levels of Kirkpatrick's training evaluation model.
      Each can be used for replication by state, local, and tribal public health
      professionals.

PMID- 25072485
TI  - The development of a model of psychological first aid for non-mental health
      trained public health personnel: the Johns Hopkins RAPID-PFA.
AB  - INTRODUCTION: The Johns Hopkins Center for Public Health Preparedness, which
      houses the Centers for Disease Control and Prevention-funded Preparedness and
      Emergency Response Learning Center, has been addressing the challenge of disaster
      caused behavioral health surge by conducting training programs in psychological
      first aid (PFA) for public health professionals. This report describes our
      approach, named RAPID-PFA, and summarizes training evaluation data to determine
      if relevant knowledge, skills, and attitudes are imparted to trainees to support
      effective PFA delivery. BACKGROUND/RATIONALE: In the wake of disasters, there is
      an increase in psychological distress and dysfunction among survivors and first
      responders. To meet the challenges posed by this surge, a professional workforce
      trained in PFA is imperative. METHODS/ACTIVITY: More than 1500 participants
      received a 1-day RAPID-PFA training. Pre-/postassessments were conducted to
      measure (a) required knowledge to apply PFA; (b) perceived self-efficacy, that
      is, belief in one's own ability, to apply PFA techniques; and (c) confidence in
      one's own resilience in a crisis context. Statistical techniques were used to
      validate the extent to which the survey successfully measured individual PFA
      constructs, that is, unidimensionality, and to quantify the reliability of the
      assessment tool. RESULTS/OUTCOME: Statistically significant pre-/postimprovements
      were observed in (a) knowledge items supportive of PFA delivery, (b) perceived
      self-efficacy to apply PFA interventions, and (c) confidence about being a
      resilient PFA provider. Cronbach alpha coefficients ranging from 0.87 to 0.90
      suggested that the self-reported measures possessed sufficient internal
      consistency. DISCUSSION: Findings were consistent with our pilot work, and with
      our complementary research initiatives validating a variant of RAPID-PFA with
      faith communities. LESSONS LEARNED/NEXT STEPS: The RAPID-PFA model promises to be
      a broadly applicable approach to extending community behavioral health surge
      capacity. Relevant next steps include evaluating the effectiveness of trained
      providers in real crisis situations, and determining if PFA training may have
      potential beyond the disaster context.

PMID- 25072486
TI  - A resilient nation--critical to national and global health security.

PMID- 25072487
TI  - Lessons learned in testing the feasibility of evaluating transfer of training to
      an operations setting.
AB  - INTRODUCTION: The purpose of the study was to explore the feasibility, identify
      challenges, and offer solutions to evaluating transfer of training to the
      operations setting. BACKGROUND: The assumption underlying public health emergency
      preparedness training is competencies and capabilities will transfer to the
      operations setting. However, there are no studies describing methods for
      evaluating the transfer of training. METHODS: An online training course that
      mimicked field decision making was selected. A functional exercise was developed
      and aligned with the goals and objectives of the online course. Transfer of
      training was assessed at the individual capability level and at the agency level
      by examining changes in emergency operating plans. CONCLUSIONS: It was concluded
      the ability to evaluate transfer of training to an operations setting is
      feasible. However, it requires more deliberate and coordinated planning between
      the exercise and the training than the current status quo. LESSONS LEARNED: Eight
      lessons learned are shared including the need to design training courses to align
      to an operation-based exercise, and not vice versa, the need to rely on
      qualitative approaches, and the need for an a priori evaluation rubric.

PMID- 25072488
TI  - Planning and executing complex large-scale exercises.
AB  - INTRODUCTION: Increasingly, public health departments are designing and engaging
      in complex operations-based full-scale exercises to test multiple public health
      preparedness response functions. The Department of Homeland Security's Homeland
      Security Exercise and Evaluation Program (HSEEP) supplies benchmark guidelines
      that provide a framework for both the design and the evaluation of drills and
      exercises; however, the HSEEP framework does not seem to have been designed to
      manage the development and evaluation of multiple, operations-based, parallel
      exercises combined into 1 complex large-scale event. METHODS: Lessons learned
      from the planning of the Mississippi State Department of Health Emergency Support
      Function--8 involvement in National Level Exercise 2011 were used to develop an
      expanded exercise planning model that is HSEEP compliant but accounts for
      increased exercise complexity and is more functional for public health. RESULTS:
      The Expanded HSEEP (E-HSEEP) model was developed through changes in the HSEEP
      exercise planning process in areas of Exercise Plan, Controller/Evaluator
      Handbook, Evaluation Plan, and After Action Report and Improvement Plan
      development. The E-HSEEP model was tested and refined during the planning and
      evaluation of Mississippi's State-level Emergency Support Function-8 exercises in
      2012 and 2013. DISCUSSION: As a result of using the E-HSEEP model, Mississippi
      State Department of Health was able to capture strengths, lessons learned, and
      areas for improvement, and identify microlevel issues that may have been missed
      using the traditional HSEEP framework. NEXT STEPS: The South Central Preparedness
      and Emergency Response Learning Center is working to create an Excel-based E
      HSEEP tool that will allow practice partners to build a database to track
      corrective actions and conduct many different types of analyses and comparisons.

PMID- 25072489
TI  - Adaptive scenarios: a training model for today's public health workforce.
AB  - INTRODUCTION: With the current economic climate, money for training is scarce. In
      addition, time is a major barrier to participation in trainings. To meet the
      public health workforce's rising demand for training, while struggling with less
      time and fewer resources, the Upper Midwest Preparedness and Emergency Response
      Learning Center has developed a model of online training that provides the public
      health workforce with individually customized, needs-based training experiences.
      BACKGROUND/RATIONALE: Adaptive scenarios are rooted in case-based reasoning, a
      learning approach that focuses on the specific knowledge needed to solve a
      problem. Proponents of case-based reasoning argue that learners benefit from
      being able to remember previous similar situations and reusing information and
      knowledge from that situation. Adaptive scenarios based on true-to-life job
      performance provide an opportunity to assess skills by presenting the user with
      choices to make in a problem-solving context. METHODS/ACTIVITIES: A team approach
      was used to develop the adaptive scenarios. Storylines were developed that
      incorporated situations aligning with the knowledge, skills, and attitudes
      outlined in the Public Health Preparedness and Response Core Competency Model.
      This article examines 2 adaptive scenarios: "Ready or Not? A Family Preparedness
      Scenario" and "Responding to a Crisis: Managing Emotions and Stress Scenario."
      RESULTS/OUTCOMES: The scenarios are available on Upper Midwest Preparedness and
      Emergency Response Learning Center's Learning Management System, the Training
      Source (http://training-source.org). Evaluation data indicate that users'
      experiences have been positive. DISCUSSION: Integrating the assessment and
      training elements of the scenarios so that the training experience is uniquely
      adaptive to each user is one of the most efficient ways to provide training. The
      opportunity to provide individualized, needs-based training without having to
      administer separate assessments has the potential to save time and resources.
      LESSONS LEARNED/NEXT STEPS: These adaptive scenarios continue to be marketed to
      target audiences through partner organizations, various Web sites, electronic
      newsletters, and social media. Next steps include the implementation of a 6-month
      follow-up evaluation, using Kirkpatrick level III. Kirkpatrick level III
      evaluation measures whether there was actual transfer of learning to the work
      setting.

PMID- 25072490
TI  - Using a digital story format: a contemporary approach to meeting the workforce
      needs of public health laboratories.
AB  - INTRODUCTION: Public health laboratories are an integral partner in preparedness
      and emergency response. The Upper Midwest Preparedness and Emergency Response
      Learning Center (UMPERLC) and the State Hygienic Laboratory at the University of
      Iowa have a long history of working together to identify and meet the
      preparedness training needs of the laboratory workforce. The training, Anatomy of
      a Foodborne Outbreak, which uses a digital story format, provides an example of
      this partnership. BACKGROUND/RATIONALE: The State Hygienic Laboratory expressed
      the need for training programs targeted at enhancing early detection and
      investigation of outbreaks. Clinical laboratory staff play a significant role in
      identifying patient samples that may represent the effects of foodborne illness.
      Given that foodborne illnesses are on the increase nationally, it is critical
      that laboratory staff be prepared to deal with these outbreaks. METHODS/ACTIVITY:
      UMPERLC collaborated with State Hygienic Laboratory content experts in the design
      and development of a digital story, using a foodborne outbreak that focuses on
      testing to detect Shiga toxin-producing Escherichia coli. This narrative format
      was selected because seeing and hearing a story about the training content
      provide the learner with a deeper interaction and richer learning experience,
      allowing the learner to better see the bigger picture. RESULTS/OUTCOMES: Anatomy
      of a Foodborne Outbreak is available on UMPERLC's Learning Management System,
      Training Source (http://training-source.org). Evaluation data indicate positive
      learning experiences overall. DISCUSSION: The digital story format, which is a
      video that uses a blend of images, text, and audio narration, was an appropriate
      method for the content and learning outcomes of the Anatomy of a Foodborne
      Outbreak training. This format requires more active learning, which increases
      retention and transfer of knowledge. Training that is easily accessed and user
      friendly is an important resource for laboratory staff. LESSONS LEARNED/NEXT
      STEPS: When reviewing the course completion data, the highest enrollment occurred
      immediately after the training program was released. To increase visibility,
      Anatomy of a Foodborne Outbreak is housed on both the State Hygienic Laboratory
      Web site and UMPERLC's Learning Management System. The course has also been added
      to national learning databases such as the Centers for Disease Control and
      Prevention TrainingFinder Real-time Affiliate Integrated Network (CDC TRAIN) and
      Certified in Public Health Recertification & Reporting System.

PMID- 25072491
TI  - Using gaming simulation to evaluate bioterrorism and emergency readiness
      training.
AB  - INTRODUCTION: The University of Minnesota: Simulations, Exercises and Effective
      Education: Preparedness and Emergency Response Learning Center uses simulations,
      which allow trainees to participate in realistic scenarios, to develop and
      evaluate competency. BACKGROUND/RATIONALE: In a previous study, participants in
      Disaster in Franklin County: A Public Health Simulation demonstrated that prior
      bioterrorism and emergency readiness training (BT/ER) is significantly associated
      with better performance in a simulated emergency. We conducted a second analysis
      with a larger data set, remapping simulation questions to the Public Health
      Preparedness and Response Core Competency Model, Version 1.0. METHODS/ACTIVITY:
      We performed an outcome evaluation of the impact of public health preparedness
      training. In particular, we compared individuals with significant BT/ER training
      to individuals without training on the basis of performance in a simulated
      emergency. We grouped participants as group 1 (>=45 hours of BT/ER training) and
      group 2 (<45 hours). Dependent variables included effectiveness of chosen
      responses within the gaming simulation, which was measured as the proportion of
      questions answered correctly for each participant. The relationship of
      effectiveness with significant BT/ER training was estimated using either multiple
      linear or logistic regression. RESULTS/OUTCOMES: For overall effectiveness, group
      1 had 2% more correct decisions, on average, than group 2 (P < .001). Group 1
      performed significantly better, on average, than group 2 for competency 1.1 (P =
      .001) and competency 2.3 (P < .001). However, group 1 was significantly worse on
      competency 1.2 than group 2. DISCUSSION: Results indicate that prior training is
      significantly associated with better performance in a simulated emergency using
      gaming technology. Effectiveness differed by competency, indicating that more
      training may be needed in certain competency areas. NEXT STEPS: Next steps to
      enhancing the usefulness of simulations in training should go beyond questioning
      if the learner learned and included questions related to the organizational
      factors that contributed to simulation effectiveness, and attributes of the
      simulation that encouraged competency and capacity building.

PMID- 25072492
TI  - Measurement, geospatial, and mechanistic models of public health hazard
      vulnerability and jurisdictional risk.
AB  - CONTEXT: County and state health departments are increasingly conducting hazard
      vulnerability and jurisdictional risk (HVJR) assessments for public health
      emergency preparedness and mitigation planning and evaluation to improve the
      public health disaster response; however, integration and adoption of these
      assessments into practice are still relatively rare. While the quantitative
      methods associated with complex analytic and measurement methods, causal
      inference, and decision theory are common in public health research, they have
      not been widely used in public health preparedness and mitigation planning.
      OBJECTIVE: To address this gap, the Harvard School of Public Health PERLC's goal
      was to develop measurement, geospatial, and mechanistic models to aid public
      health practitioners in understanding the complexity of HVJR assessment and to
      determine the feasibility of using these methods for dynamic and predictive HVJR
      analyses. METHODS: We used systematic reviews, causal inference theory,
      structural equation modeling (SEM), and multivariate statistical methods to
      develop the conceptual and mechanistic HVJR models. Geospatial mapping was used
      to inform the hypothetical mechanistic model by visually examining the
      variability and patterns associated with county-level demographic, social,
      economic, hazards, and resource data. A simulation algorithm was developed for
      testing the feasibility of using SEM estimation. RESULTS: The conceptual model
      identified the predictive latent variables used in public health HVJR tools
      (hazard, vulnerability, and resilience), the outcomes (human, physical, and
      economic losses), and the corresponding measurement subcomponents. This model was
      translated into a hypothetical mechanistic model to explore and evaluate causal
      and measurement pathways. To test the feasibility of SEM estimation, the
      mechanistic model path diagram was translated into linear equations and solved
      simultaneously using simulated data representing 192 counties. CONCLUSIONS:
      Measurement, geospatial, and mechanistic models can be used to confirm and
      validate existing and proposed HVJR models and potentially increase the
      predictive validity of these models for optimizing and improving public health
      preparedness planning.

PMID- 25072493
TI  - A public health hazard mitigation planning process.
AB  - INTRODUCTION: The Texas A&M Health Science Center School of Rural Public Health,
      a member of the Training and Education Collaborative System Preparedness and
      Emergency Response Learning Center (TECS-PERLC), has long-standing partnerships
      with 2 Health Service Regions (Regions) in Texas. TECS-PERLC was contracted by
      these Regions to address 2 challenges identified in meeting requirements outlined
      by the Risk-Based Funding Project. First, within Metropolitan Statistical Areas,
      there is not a formal authoritative structure. Second, preexisting tools and
      processes did not adequately satisfy requirements to assess public health,
      medical, and mental health needs and link mitigation strategies to the Public
      Health Preparedness Capabilities, which provide guidance to prepare for, respond
      to, and recover from public health incidents. METHODS: TECS-PERLC, with its
      partners, developed a framework to interpret and apply results from the Texas
      Public Health Risk Assessment Tool (TxPHRAT). The 3-phase community engagement
      based TxPHRAT Mitigation Planning Process (Mitigation Planning Process) and
      associated tools facilitated the development of mitigation plans. Tools included
      (1) profiles interpreting TxPHRAT results and identifying, ranking, and
      prioritizing hazards and capability gaps; (2) a catalog of intervention
      strategies and activities linked to hazards and capabilities; and (3) a template
      to plan, evaluate, and report mitigation planning efforts. OUTCOMES: The
      Mitigation Planning Process provided a framework for Regions to successfully
      address all funding requirements. TECS-PERLC developed more than 60 profiles,
      cataloged and linked 195 intervention strategies, and developed a template
      resulting in 20 submitted mitigation plans. DISCUSSION: A public health-focused,
      community engagement-based mitigation planning process was developed by TECS
      PERLC and successfully implemented by the Regions. The outcomes met all
      requirements and reinforce the effectiveness of academic practice partnerships
      and importance of community engagement in mitigation planning. NEXT STEPS:
      Additional funding has been approved to expand the Mitigation Planning Process to
      all counties in Texas with local health departments.

PMID- 25072494
TI  - Preparedness and Emergency Response Learning Centers: supporting the workforce
      for national health security.
AB  - The importance of a competent and prepared national public health workforce,
      ready to respond to threats to the public's health, has been acknowledged in
      numerous publications since the 1980s. The Preparedness and Emergency Response
      Learning Centers (PERLCs) were funded by the Centers for Disease Control and
      Prevention in 2010 to continue to build upon a decade of focused activities in
      public health workforce preparedness development initiated under the Centers for
      Public Health Preparedness program (http://www.cdc.gov/phpr/cphp/). All 14 PERLCs
      were located within Council on Education for Public Health (CEPH) accredited
      schools of public health. These centers aimed to improve workforce readiness and
      competence through the development, delivery, and evaluation of targeted learning
      programs designed to meet specific requirements of state, local, and tribal
      partners. The PERLCs supported organizational and community readiness locally,
      regionally, or nationally through the provision of technical consultation and
      dissemination of specific, practical tools aligned with national preparedness
      competency frameworks and public health preparedness capabilities. Public health
      agencies strive to address growing public needs and a continuous stream of
      current and emerging public health threats. The PERLC network represented a
      flexible, scalable, and experienced national learning system linking academia
      with practice. This system improved national health security by enhancing
      individual, organizational, and community performance through the application of
      public health science and learning technologies to frontline practice. 

PMID- 25072495
TI  - Accelerating preparedness: leveraging the UNC PERLC to improve other projects
      related to public health surveillance, assessment, and regionalization.
AB  - The co-location of the University of North Carolina at Chapel Hill (UNC)
      Preparedness and Emergency Response Learning Center (PERLC) and the UNC
      Preparedness and Emergency Response Research Center (PERRC) and other smaller
      projects within the North Carolina Institute for Public Health, a public health
      practice-oriented unit of the UNC Gillings School of Global Public Health,
      facilitated many successful collaborations. By sharing personnel, space, and
      other resources, the UNC PERLC and PERRC and other projects were able to meet the
      needs of the public health workforce by developing evidence-based training
      programs and tools around topics including epidemiology, surveillance, and
      vulnerable populations. 

PMID- 25072496
TI  - Disaster planning for vulnerable populations: leveraging Community Human Service
      Organizations direct service delivery personnel.
AB  - INTRODUCTION: Given the variability, complexities, and available resources for
      local vulnerable populations, it is clear that preparing effectively for
      catastrophic events cannot be accomplished with a single, simple template.
      Inclusion of Community Human Service Organizations' (CHSO's) direct service
      delivery personnel ensures that emergency disaster planning efforts for
      vulnerable populations are effective and responsive to unique needs and
      constraints. By leveraging existing local resources, it extends the preparedness
      system's reach to the whole community. BACKGROUND: CHSO personnel already perform
      community-based services and directly engage with vulnerable and special needs
      populations; typically they are on the front lines during an emergency event.
      Generally, however, the CHSOs, staff, and clients are neither adequately prepared
      for disasters nor well integrated into emergency systems. To address preparedness
      gaps identified during Hurricane Sandy, regional CHSO and local health department
      partners requested that the Columbia Regional Learning Center provide
      preparedness trainings for their agencies and staff responsible for vulnerable
      clients. METHODS: Evaluation of this initiative was begun with a mixed-methods
      approach consisting of collaborative learning activities, a function-based
      assessment tool, and a 5 Steps to Preparedness module. RESULTS: Results from a
      survey were inclusive because of a low response rate but suggested satisfaction
      with the training format and content; increases in awareness of a client
      preparedness role; and steps toward improved personal, agency, and client
      preparedness. DISCUSSION: Direct service delivery personnel can leverage routine
      client interactions for preparedness planning and thus can contribute
      significantly to vulnerable population and community disaster readiness.
      Trainings that provide preparedness tools can help support this role. LESSONS
      LEARNED: CHSO personnel are knowledgeable and have the expertise to assist
      clients in personal preparedness planning; yet, there are challenges around their
      ability and willingness to take on additional responsibilities.

PMID- 25072497
TI  - Maximizing resources with mini-grants: enhancing preparedness capabilities and
      capacity in public health organizations.
AB  - INTRODUCTION: The Illinois Preparedness and Response Learning Center engages in
      efforts to develop and maintain a competent, sustainable, and prepared public
      health workforce in Illinois. Training, education, and technical assistance
      activities are driven by assessments conducted to identify preparedness gaps,
      needs, and priorities of public health organizations and the communities they
      serve. BACKGROUND: Many public health organizations face limited resources to
      engage in activities they identify as essential to building preparedness and
      response capabilities and capacity. In response to this challenge, the Illinois
      Preparedness and Response Learning Center adapted a mini-grant program to support
      short-term, targeted preparedness-related activities for which there was a need
      but no discretionary resources available. METHODS: A mini-grant program was
      implemented on the basis of a request for proposals, with projects funded for a 6
      month period. An evaluation was conducted at 6 and 12 months to assess the impact
      of the local project on the capabilities and capacity of the organizations that
      participated. RESULTS: Thirteen projects were funded in local health departments
      and other organizations in a variety of communities across Illinois. Evaluation
      results indicate that these short-term projects contributed to the organization's
      preparedness efforts and local partnerships 6 and 12 months after funding ended.
      DISCUSSION: Even relatively small amounts of funding can assist public health
      agencies and their community partners in improving capabilities and building
      organizational and community capacity. LESSONS LEARNED: (1) The mini-grant
      program model can help develop and cultivate preparedness partnership between
      academia and practice to achieve positive outcomes despite limited funding. (2)
      Funding self-assessed needs of organizations through a mini-grant process may
      have value for larger programs without the staff resources or time to provide
      customized preparedness services to a large target market/service area. (3) There
      appear to be benefits to channeling small amounts of funding to address targeted
      needs and gaps identified by organizations.

PMID- 25072498
TI  - Weaving latino cultural concepts into Preparedness Core Competency training.
AB  - INTRODUCTION: The New York * New Jersey Preparedness and Emergency Response
      Learning Center (NY*NJ PERLC) is one of 14 Centers funded by the Centers for
      Disease Control and Prevention designed to address the preparedness and response
      training and education needs of the public health workforce. One of the important
      niches, or focus areas for the Center, is training to improve the capacity of
      public health workers to respond with competence to the needs of vulnerable
      populations. BACKGROUND: During every phase of a disaster, racial and ethnic
      minorities, including Latinos, suffer worse outcomes than the general population.
      Communities with diverse cultural origins and limited English speakers often
      present more complex issues during public health emergencies. Training that
      incorporates cultural concepts into the Preparedness Core Competencies may
      improve the ability of public health workers to engage the Latino community in
      preparedness activities and ultimately improve outcomes during disasters.
      METHODS: This article describes initiatives undertaken by the NY*NJ PERLC to
      improve the capacity of the public health workforce to respond competently to the
      needs of Latino populations. In 2012, the Center collaborated with national,
      state, and local partners to develop a nationwide broadcast founded on the
      Preparedness Core Competencies, Latinos During Emergencies: Cultural
      Considerations Impacting Disaster Preparedness. The widely viewed broadcast (497
      sites in 47 states and 13 nations) highlighted the commonalities and differences
      within Latino culture that can impact emergency preparedness and response and
      outlined practical strategies to enhance participation. OUTCOMES: The success of
      the broadcast spurred a number of partner requests for training and technical
      assistance. Lessons learned from these experiences, including our "undercover"
      work at local Points of Dispensing, are incorporated into subsequent interactive
      trainings to improve the competency of public health workers. NEXT STEPS:
      Participants recommended developing similar training addressing cultural
      differences, especially for other ethnic groups.

PMID- 25072499
TI  - Serotonin 5-HT7 receptor is critically involved in acute and chronic inflammation
      of the gastrointestinal tract.
AB  - BACKGROUND: Intestinal inflammation is often associated with an increased level
      of serotonin (5-HT), an important gastrointestinal signaling molecule involved in
      gut homeostasis through stimulation of specific receptors. In this study, we
      investigated the role of 5-HT7 receptor (5-HT7R) in the induction and development
      of intestinal inflammation using a mouse model of acute and chronic colitis and
      human patients with Crohn's disease (CD). METHODS: Acute colitis was induced
      through administration of dextran sodium sulfate to wild-type, 5-HT7R-deficient
      mice and hematopoietic bone marrow chimera. Chronic colitis was induced in
      interleukin 10-deficient mice. The role of 5-HT7R in gut inflammation was
      assessed using agonist/antagonist treatment. We investigated expression and
      distribution of 5-HT7R, extent of gut inflammation with magnetic resonance
      imaging and histological analysis, survival rate, and disease activity index.
      Finally, biopsies from the large intestine of patients with CD were analyzed.
      RESULTS: Under basal conditions, 5-HT7R is expressed both in enteric neurons and
      CD11c cells of the large intestine. Expression of 5-HT7R significantly increased
      after induction of colitis in mice and in inflamed intestinal regions of patients
      with CD in CD11c/CD86 double-positive cells. Pharmacological blockade or genetic
      ablation of 5-HT7R resulted in increased severity of both acute and chronic
      dextran sodium sulfate-induced colitis, whereas receptor stimulation showed an
      anti-inflammatory effect. Analysis of bone marrow chimera indicated importance of
      5-HT7R expressed by hematopoietic cells in intestinal inflammation. CONCLUSIONS:
      The 5-HT7R expressed on CD11c/CD86-positive myeloid cells modulates the severity
      of intestinal inflammation in an acute and chronic colitis and thus represents a
      potential therapeutic target for the treatment of inflammatory disorders such as
      CD.

PMID- 25072500
TI  - Smoking cessation alters intestinal microbiota: insights from quantitative
      investigations on human fecal samples using FISH.
AB  - BACKGROUND: There has been a dramatic increase in investigations on the potential
      mechanistic role of the intestinal microbiota in various diseases and factors
      modulating intestinal microbial composition. We recently reported on intestinal
      microbial shifts after smoking cessation in humans. In this study, we aimed to
      conduct further microbial analyses and verify our previous results obtained by
      pyrosequencing using a direct quantitative microbial approach. METHODS: Stool
      samples of healthy smoking human subjects undergoing controlled smoking cessation
      during a 9-week observational period were analyzed and compared with 2 control
      groups, ongoing smoking and nonsmoking subjects. Fluorescence in situ
      hybridization was applied to quantify specific bacterial groups. RESULTS:
      Intestinal microbiota composition was substantially altered after smoking
      cessation as characterized by an increase in key representatives from the phyla
      of Firmicutes (Clostridium coccoides, Eubacterium rectale, and Clostridium leptum
      subgroup) and Actinobacteria (HGC bacteria and Bifidobacteria) as well as a
      decrease in Bacteroidetes (Prevotella spp. and Bacteroides spp.) and
      Proteobacteria (beta- and gamma-subgroup of Proteobacteria). CONCLUSIONS: As
      determined by fluorescence in situ hybridization, an independent direct
      quantitative microbial approach, we could confirm that intestinal microbiota
      composition in humans is influenced by smoking. The characteristics of observed
      microbial shifts suggest a potential mechanistic association to alterations in
      body weight subsequent to smoking cessation. More importantly, regarding
      previously described microbial hallmarks of dysbiosis in inflammatory bowel
      diseases, a variety of observed microbial alterations after smoking cessation
      deserve further consideration in view of the divergent effect of smoking on the
      clinical course of Crohn's disease and ulcerative colitis.

PMID- 25072501
TI  - Approach and management of patients with chronic hepatitis B and C during the
      course of inflammatory bowel disease.
AB  - Inflammatory bowel disease and chronic viral hepatitis are 2 distinct but common
      conditions throughout the world. Mostly, both need life-long follow-up. Since
      immunosuppressive drugs remain corner stones of inflammatory bowel disease
      management, one should be aware of the concomitant presence of chronic viral
      hepatitis in such patients to prevent serious (even fatal) outcomes. Recently,
      new treatment options have become available in the treatment of both inflammatory
      bowel disease and chronic viral hepatitis. In this review, we have discussed and
      summarized current treatment and follow-up strategies for those 2 important
      public health issues in light of available literature.

PMID- 25072502
TI  - Drug therapies for ulcerative proctitis: systematic review and meta-analysis.
AB  - BACKGROUND: Patients with ulcerative colitis limited to the proctum are
      considered to have ulcerative proctitis (UP). In patients with more extensive
      ulcerative colitis, treatment occurs in a step-up fashion (5-ASA,
      corticosteroids, thiopurines, anti-TNF-alpha agents), a strategy which has proven
      effective. Although treatment of UP occurs using the same step-up design, the
      efficacy of these therapies in UP is scarcely studied. The objectives were to
      systematically review the literature for randomized controlled trials studying
      drug therapies for induction and maintenance of remission in patients with UP.
      METHODS: Electronic databases and reference lists of review articles were
      searched. The primary outcomes were clinical remission induction rate and the
      maintained clinical remission rate. Secondary outcomes were induction and
      maintenance of endoscopic and histological remission. Relative risks (RR) and 95%
      confidence intervals (CI) for were calculated. RESULTS: Twenty-three studies
      (1834 patients) were included. Eighteen trials investigated induction and 5
      studied maintenance of remission. Topical 5-ASA was significantly superior to
      placebo for induction (RR, 2.39; 95% CI, 1.63-3.51) and maintenance (RR, 2.80;
      95% CI, 1.21-6.45) of clinical remission, regardless of dose or formulation.
      Subgroup analysis of 5-ASA suppositories also showed superiority over placebo for
      induction of clinical (RR, 3.07; 95% CI, 1.70-5.55) and endoscopic remission (RR,
      2.64; 95% CI, 1.85-3.77). CONCLUSIONS: Topical 5-ASA is superior to placebo for
      the induction and maintenance of clinical remission and for the induction of
      endoscopic remission. The efficacy of corticosteroids, thiopurines, and anti
      TNFalpha has been insufficiently studied in patients with UP.

PMID- 25072503
TI  - Syndecan 4 signaling and intervertebral disc degeneration.
AB  - This commentary highlights the article by Wang et al, exploring the regulatory
      relationship between matrix metalloproteinase-3 and syndecan 4 in disc
      degeneration. 

PMID- 25072504
TI  - Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in
      breast cancer patients: diffusion-weighted MRI and conventional MRI.
AB  - PURPOSES: To evaluate the diagnostic value of diffusion-weighted MRI (DWI) and
      combination of conventional MRI and DWI to predict metastatic axillary lymph
      nodes in breast cancer. MATERIALS AND METHODS: Two hundred fifty-two breast
      cancer patients with 253 axillae were included. The morphological parameters on
      axial T2-weighted images without fat saturation and apparent diffusion
      coefficient (ADC) values were retrospectively analyzed. An independent t-test/chi
      square test and receiver operating characteristics (ROC) curve analysis were
      used. RESULTS: On conventional MRI, short and long axis length, maximal cortical
      thickness, relative T2 value, loss of fatty hilum (p<0.001 for each), and
      eccentric cortical thickening (p<0.003) were statistically significantly
      different between the metastatic and nonmetastatic groups. The short axis to long
      axis ratio was not a statistically significant parameter. The ADC value was
      significantly different between the 2 groups, with an AUC that was higher than
      that of conventional MR parameters (AUC, 0.815; threshold, <=0.986*10-3
      mm(2)/sec; sensitivity, 75.8%; specificity, 83.9%). Using the adopted thresholds
      for each parameter, a total number of findings suggesting malignancy of 4 or
      higher was determined as the threshold, with high specificity (90.1%).
      CONCLUSION: Using conventional MRI and DWI, we can evaluate the axilla in breast
      cancer with high specificity.

PMID- 25072506
TI  - Performance monitoring during associative learning and its relation to obsessive
      compulsive characteristics.
AB  - Neural responses to performance errors and external feedback have been suggested
      to be altered in obsessive-compulsive disorder. In the current study, an
      associative learning task was used in healthy participants assessed for obsessive
      compulsive symptoms by the OCI-R questionnaire. The task included a condition
      with equivocal feedback that did not inform about the participants' performance.
      Following incorrect responses, an error-related negativity and an error
      positivity were observed. In the feedback phase, the largest feedback-related
      negativity was observed following equivocal feedback. Theta and beta oscillatory
      components were found following incorrect and correct responses, respectively,
      and an increase in theta power was associated with negative and equivocal
      feedback. Changes over time were also explored as an indicator for possible
      learning effects. Finally, event-related potentials and oscillatory components
      were found to be uncorrelated with OCI-R scores in the current non-clinical
      sample. 

PMID- 25072505
TI  - Sonic hedgehog-Gli1 signaling pathway regulates the epithelial mesenchymal
      transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer
      cells.
AB  - AIMS: The hedgehog signaling pathway plays an important role in EMT of pancreatic
      cancer cells, but the precise mechanisms remain elusive. Because S100A4 as a key
      EMT moleculer marker was found to be upregulated upon Gli1 in pancreatic cancer
      cells, we focused on the relationship between Shh-Gli1 signals and S100 genes
      family. METHODS: On the base of cDNA microarray data, we investigated regulating
      mechanism of Gli1 to some members of S100A genes family in pancreatic cancer cell
      lines firstly. Then, the regulation of Gli1 to S100A4 gene was studied by
      molecular biology assays and the pro-metastasis effection of Gli1-dependent
      S100A4 was investigated in vitro. Finally, the expressions of Shh, Gli1, S100A4
      and E-cadherin in pancreatic cancer tissues were studied by using
      immunohistochemistry assays. RESULTS: Five members of the S100 genes family,
      S100A2, S100A4, S100A6, S100A11, and S100A14 were found to be downregulated
      significantly upon Gli1 knockdown. Gli1 enhancer prediction combining with in
      vitro data demonstrated that Gli1 primarily regulates S100A family members via
      cis-acting elements. Indeed, the data indicate S100A4 and vimentin genes were
      upregulated significantly by Shh/Gli1-expression increasing and E-cadherin was
      significantly reduced at the same time. Migration of PC cells was increased
      significantly in a dose-dependent manner of Gli1 expression (P<0.05) and siS100A4
      significantly reversed the response of PC cells induced by L-Shh transduction
      (P<0.01). CONCLUSION: Our data establish a novel connection between Shh-Gli1
      signaling and S100A4 regulation, which imply that S100A4 might be one of the key
      factors in EMT mediated by Shh-Gli1 signaling in pancreatic cancer.

PMID- 25072507
TI  - A prospective development study investigating focal irreversible electroporation
      in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial
      (NEAT).
AB  - INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments
      while maintaining the oncological benefit. Irreversible electroporation (IRE) has
      been proposed to be tissue selective and so might have favourable characteristics
      compared to the currently used prostate ablative technologies. The aim of this
      trial is to determine the adverse events, genito-urinary side effects and early
      histological outcomes of focal IRE in men with localised prostate cancer.
      METHODS: This is a single centre prospective development (stage 2a) study
      following the IDEAL recommendations for evaluating new surgical procedures.
      Twenty men who have MRI-visible disease localised in the anterior part of the
      prostate will be recruited. The sample size permits a precision estimate around
      key functional outcomes. Inclusion criteria include PSA <= 15 ng/ml, Gleason
      score <= 4 + 3, stage T2N0M0 and absence of clinically significant disease
      outside the treatment area. Treatment delivery will be changed in an adaptive
      iterative manner so as to allow optimisation of the IRE protocol. After focal
      IRE, men will be followed during 12 months using validated patient reported
      outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease
      control will be evaluated by mpMRI and targeted transperineal biopsy of the
      treated area at 6 months. DISCUSSION: The NEAT trial will assess the early
      functional and disease control outcome of focal IRE using an adaptive design. Our
      protocol can provide guidance for designing an adaptive trial to assess new
      surgical technologies in the challenging landscape of health technology
      assessment in prostate cancer treatment.

PMID- 25072508
TI  - In vivo detection of macrophage recruitment in hind-limb ischemia using a
      targeted near-infrared fluorophore.
AB  - Macrophages are an essential component of the immune system and have protective
      and pathogenic functions in various diseases. Imaging of macrophages in vivo
      could furnish new tools to advance evaluation of disease and therapies. Critical
      limb ischemia is a disease in which macrophages have considerable pathogenic
      roles, and are potential targets for cell-based immunotherapy. We sought to
      develop a new near-infrared fluorescence (NIRF) imaging probe to target
      macrophages specifically in vivo in various pathological states, including hind
      limb ischemia. We rapidly screened the photostable cyanine-based NIRF library
      against different blood cell lines. The identified monocyte/macrophage-selective
      hit was tested in vitro in live-cell labeling assay. Non-invasive NIRF imaging
      was performed with murine models of paw inflammation by lipopolysaccharide
      challenge and hind-limb ischemia with femoral artery ligation. in vivo macrophage
      targeting was further evaluated using intravital microscopy with Csf1r-EGFP
      transgenic mice and immunofluorescent staining with macrophage-specific markers.
      We discovered MF800, a Macrophage-specific near-infrared Fluorophore, which
      showed selective live-cell imaging performance in a panel of cell lines and
      primary human blood samples. MF800 outperforms the clinically-available NIRF
      contrast agent ICG for in vivo specificity in paw inflammation and hind-limb
      ischemia models. We observed a marked overlap of MF800-labeled cells and EGFP
      expressing macrophages in intravital imaging of Csf1r-EGFP transgenic mice. In
      the histologic analysis, MF800-positive cells also expressed the macrophage
      markers CD68 and CD169. NIRF imaging showcased the potential of using MF800 to
      understand macrophage behavior in vivo, characterize macrophage-associated
      diseases, and may help in assessing therapeutic responses in the clinic. 

PMID- 25072509
TI  - Pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of 5-fluorouracil
      for erythropenia in rats.
AB  - INTRODUCTION: The aim of the present study was to develop a simple
      pharmacokinetic-pharmacodynamic (PK-PD) model in rats that could predict the
      onset and degree of erythropenia, a severely toxic side effect that severely
      limits the use of the anticancer agent 5-fluorouracil (5-FU). METHODS: Total
      erythrocyte counts, hemoglobin (Hb) concentrations, and hematocrit (Hct) levels
      were measured in rats following the intravenous bolus administration of 5-FU for
      4 days in order to obtain data for an analysis of the PK-PD model. Our PK-PD
      model consisted of a two-compartment PK model, with two compartments for the PD
      model and nine structural PK-PD model parameters. RESULTS: After the intravenous
      bolus administration of 5, 10, or 20 mg/kg of 5-FU to rats, absolute erythrocyte
      counts, Hb concentrations, and Hct levels transiently decreased, reached minimum
      levels on Days 7-14, and then returned to baseline levels. The nadir values
      (Cnadir) for rats treated with 5, 10, or 20 mg/kg of 5-FU were significantly
      decreased to approximately 79.4, 76.3, or 46.5% of the baseline value (Cbaseline)
      in erythrocyte counts, 86.3, 83.3, or 45.7% of Cbaseline in Hb concentrations,
      88.6, 85.5, or 47.1% of Cbaseline in Hct levels, respectively. The PK-PD model
      effectively captured the features of erythropenia and Cnadir after 5-FU
      chemotherapy. This PK-PD model was successfully used to characterize the learner
      relationship between the area under the plasma 5-FU concentration-time curve
      (AUC0-infinity) following the intravenous bolus administration of 5-FU and the
      Cnadir in erythrocyte counts, Hb concentrations, and Hct levels after the 5-FU
      treatment. DISCUSSION: The results of the present study suggest that the
      administration of a pharmacokinetically modified dose of 5-FU could minimize the
      Cnadir in erythrocyte counts, Hb concentrations, and Hct levels following the
      administration of 5-FU. The PK-PD model and simulation represent valuable
      approaches for quantifying and predicting erythropenia as well as determining
      individual doses and the time at which the subsequent course of the treatment
      should start.

PMID- 25072510
TI  - Organosulfates from pinene and isoprene over the Pearl River Delta, South China:
      seasonal variation and implication in formation mechanisms.
AB  - Biogenic organosulfates (OSs) are important markers of secondary organic aerosol
      (SOA) formation involving cross reactions of biogenic precursors (terpenoids)
      with anthropogenic pollutants. Until now, there has been rare information about
      biogenic OSs in the air of highly polluted areas. In this study, fine particle
      (PM2.5) samples were separately collected in daytime and nighttime from summer to
      fall 2010 at a site in the central Pearl River Delta (PRD), South China. Pinene
      derived nitrooxy-organosulfates (pNOSs) and isoprene-derived OSs (iOSs) were
      quantified using a liquid chromatograph (LC) coupled with a tandem mass
      spectrometer (MS/MS) operated in negative electrospray ionization (ESI) mode. The
      pNOSs with MW 295 exhibited higher levels in fall (151 +/- 86.9 ng m(-3)) than
      summer (52.4 +/- 34.0 ng m(-3)), probably owing to the elevated levels of NOx and
      sulfate in fall when air masses mainly passed through city clusters in the PRD
      and biomass burning was enhanced. In contrast to observations elsewhere where
      higher levels occurred at nighttime, pNOS levels in the PRD were higher during
      the daytime in both seasons, indicating that pNOS formation was likely driven by
      photochemistry over the PRD. This conclusion is supported by several lines of
      evidence: the specific pNOS which could be formed through both daytime
      photochemistry and nighttime NO3 chemistry exhibited no day-night variation in
      abundance relative to other pNOS isomers; the production of the hydroxynitrate
      that is the key precursor for this specific pNOS was found to be significant
      through photochemistry but negligible through NO3 chemistry based on the
      mechanisms in the Master Chemical Mechanism (MCM). For iOSs, 2-methyltetrol
      sulfate ester which could be formed from isoprene-derived epoxydiols (IEPOX)
      under low-NOx conditions showed low concentrations (below the detection limit to
      2.09 ng m(-3)), largely due to the depression of IEPOX formation by the high NOx
      levels over the PRD. 

PMID- 25072512
TI  - K+ exchanged zeolite ZK-4 as a highly selective sorbent for CO2.
AB  - Adsorbents with high capacity and selectivity for adsorption of CO2 are currently
      being investigated for applications in adsorption-driven separation of CO2 from
      flue gas. An adsorbent with a particularly high CO2-over-N2 selectivity and high
      capacity was tested here. Zeolite ZK-4 (Si:Al ~ 1.3:1), which had the same
      structure as zeolite A (LTA), showed a high CO2 capacity of 4.85 mmol/g (273 K,
      101 kPa) in its Na(+) form. When approximately 26 at. % of the extraframework
      cations were exchanged for K(+) (NaK-ZK-4), the material still adsorbed a large
      amount of CO2 (4.35 mmol/g, 273 K, 101 kPa), but the N2 uptake became negligible
      (<0.03 mmol/g, 273 K, 101 kPa). The majority of the CO2 was physisorbed on
      zeolite ZK-4 as quantified by consecutive volumetric adsorption measurements. The
      rate of physisorption of CO2 was fast, even for the highly selective sample. The
      molecular details of the sorption of CO2 were revealed as well. Computer modeling
      (Monte Carlo, molecular dynamics simulations, and quantum chemical calculations)
      allowed us to partly predict the behavior of fully K(+) exchanged zeolite K-ZK-4
      upon adsorption of CO2 and N2 for Si:Al ratios up to 4:1. Zeolite K-ZK-4 with
      Si:Al ratios below 2.5:1 restricted the diffusion of CO2 and N2 across the cages.
      These simulations could not probe the delicate details of the molecular sieving
      of CO2 over N2. Still, this study indicates that zeolites NaK-ZK-4 and K-ZK-4
      could be appealing adsorbents with high CO2 uptake (~4 mmol/g, 101 kPa, 273 K)
      and a kinetically enhanced CO2-over-N2 selectivity. 

PMID- 25072511
TI  - Evaluation of five immunoturbidimetric assays for urinary albumin quantification
      and their impact on albuminuria categorization.
AB  - OBJECTIVES: The study was designed to evaluate the performance of five automated
      immunoturbidimetric assays to quantify urinary albumin, each corresponding to a
      combination of a reagent and an analyzer (Olympus on AU640, Roche on Cobas
      Integra, Abbott on Architect, Ortho-Clinical Diagnostics Vitros on Fusion and
      Siemens on Dimension). DESIGN AND METHODS: To assess imprecision, albumin was
      measured in three urinary pools with a mean value of 25, 66 and 131 mg/L. One
      hundred and eight patient urine samples were then used to compare each
      turbidimetric method using the Passing-Bablok regression and Bland-Altman
      analyses. Concordance of the albumin/creatinine ratio (ACR), according to the
      albuminuria classifications proposed by the KDIGO, was calculated to test the
      agreement between the different assays. RESULTS: All immunoturbidimetric methods
      evaluated in this study exhibited acceptable imprecision (CV<6%). Mean values for
      108 urine samples varied from 0.5 to 762.2 mg/L. Significant differences were
      found (p<0.05) between all methods except between Olympus and Ortho (p=1.0) and
      between Abbott and Roche (p=0.12). Regarding the albuminuria categories based on
      the ACR proposed by the KDIGO, only the classification obtained with the Roche
      method was significantly different from the four other methods (p<0.001).
      CONCLUSIONS: We demonstrated that all assays were not strictly equivalent which
      could affect ACR categories in clinical practice, suggesting the need for
      harmonization of commercial methods.

PMID- 25072514
TI  - Upon impact: the fate of adhering Pseudomonas fluorescens cells during
      nanofiltration.
AB  - Nanofiltration (NF) is a high-pressure membrane filtration process increasingly
      applied in drinking water treatment and water reuse processes. NF typically
      rejects divalent salts, organic matter, and micropollutants. However, the
      efficiency of NF is adversely affected by membrane biofouling, during which
      microorganisms adhere to the membrane and proliferate to create a biofilm. Here
      we show that adhered Pseudomonas fluorescens cells under high permeate flux
      conditions are met with high fluid shear and convective fluxes at the membrane
      liquid interface, resulting in their structural damage and collapse. These
      results were confirmed by fluorescent staining, flow cytometry, and scanning
      electron microscopy. This present study offers a "first-glimpse" of cell damage
      and death during the initial phases of bacterial adhesion to NF membranes and
      raises a key question about the role of this observed phenomena during early
      stage biofilm formation under permeate flux and cross-flow conditions. 

PMID- 25072515
TI  - Radiation effects on the flow of Powell-Eyring fluid past an unsteady inclined
      stretching sheet with non-uniform heat source/sink.
AB  - This study investigates the unsteady flow of Powell-Eyring fluid past an inclined
      stretching sheet. Unsteadiness in the flow is due to the time-dependence of the
      stretching velocity and wall temperature. Mathematical analysis is performed in
      the presence of thermal radiation and non-uniform heat source/sink. The relevant
      boundary layer equations are reduced into self-similar forms by suitable
      transformations. The analytic solutions are constructed in a series form by
      homotopy analysis method (HAM). The convergence interval of the auxiliary
      parameter is obtained. Graphical results displaying the influence of interesting
      parameters are given. Numerical values of skin friction coefficient and local
      Nusselt number are computed and analyzed. 

PMID- 25072517
TI  - Competitive reaction pathways in vibrationally induced photodissociation of
      H2SO4.
AB  - Vibrationally induced photodissociation of sulfuric acid into H2O + SO3 is
      investigated based on reactive molecular dynamics (MD) simulations. Multisurface
      adiabatic reactive MD simulations allow us to follow both, H-transfer and water
      elimination after excitation of the nu9 OH-stretching mode. Analysis of several
      thousand trajectories finds that the H2O and SO3 fragments have distinct final
      state distributions with respect to translational, rotational, and vibrational
      degrees of freedom. Rotational distributions peak at quantum numbers j <= 5 for
      water and j ~ 60 for SO3. The final state distributions should be useful in
      identifying products in forthcoming experiments. Based on the MD trajectories, a
      kinetic scheme has been developed which is able to explain most of the trajectory
      data and suggests that IVR is very rapid. Typical lifetimes of the excited
      complex range from several 10 picoseconds to hundreds of nanoseconds, depending
      on the excitation level. Including temperature and pressure profiles
      characteristic for the stratosphere in the kinetic model shows that excitations
      higher than nu9 = 4 can significantly contribute to the photolysis rate. This
      extends and specifies earlier work in that multi-level modeling is required to
      understand the significance of vibrationally induced decomposition pathways of
      sulfuric acid in the middle atmosphere. 

PMID- 25072516
TI  - Highly multiplexed and reproducible ion-current-based strategy for large-scale
      quantitative proteomics and the application to protein expression dynamics
      induced by methylprednisolone in 60 rats.
AB  - A proteome-level time-series study of drug effects (i.e., pharmacodynamics) is
      critical for understanding mechanisms of action and systems pharmacology, but is
      challenging, because of the requirement of a proteomics method for reliable
      quantification of many biological samples. Here, we describe a highly
      reproducible strategy, enabling a global, large-scale investigation of the
      expression dynamics of corticosteroid-regulated proteins in livers from
      adrenalectomized rats over 11 time points after drug dosing (0.5-66 h, N =
      5/point). The analytical advances include (i) exhaustive tissue extraction with a
      Polytron/sonication procedure in a detergent cocktail buffer, and a
      cleanup/digestion procedure providing very consistent protein yields (relative
      standard deviation (RSD%) of 2.7%-6.4%) and peptide recoveries (4.1-9.0%) across
      the 60 animals; (ii) an ultrahigh-pressure nano-LC setup with substantially
      improved temperature stabilization, pump-noise suppression, and programmed
      interface cleaning, enabling excellent reproducibility for continuous analyses of
      numerous samples; (iii) separation on a 100-cm-long column (2-MUm particles) with
      high reproducibility for days to enable both in-depth profiling and accurate
      peptide ion-current match; and (iv) well-controlled ion-current-based
      quantification. To obtain high-quality quantitative data necessary to describe
      the 11 time-points protein expression temporal profiles, strict criteria were
      used to define "quantifiable proteins". A total of 323 drug-responsive proteins
      were revealed with confidence, and the time profiles of these proteins provided
      new insights into the diverse temporal changes of biological cascades associated
      with hepatic metabolism, response to hormone stimuli, gluconeogenesis,
      inflammatory responses, and protein translation processes. Most profile changes
      persisted well after the drug was eliminated. The developed strategy can also be
      broadly applied in preclinical and clinical research, where the analysis of
      numerous biological replicates is crucial. 

PMID- 25072518
TI  - Synthesis of magnetite-silica core-shell nanoparticles via direct silicon
      oxidation.
AB  - Magnetite-silica core-shell nanoparticles (Fe3O4@SiO2 NPs) were prepared from
      silicon powder by direct oxidation without using any expensive precursors (such
      as TEOS) and organic solvents. The as-prepared Fe3O4@SiO2 NPs were characterized
      by TEM, DLS, XRD, FT-IR, zeta potential and NMR Analyzer. The results show that
      the Fe3O4@SiO2 NPs are monodispersed core-shell nanostructures with single cores
      that were uniformly coated by silica shells. The relaxation property indicates
      that Fe3O4@SiO2 NPs have desirable characteristics for T2 MRI contrast agents.
      This facile and green method is promising for large-scale production, which would
      open new opportunities for preparing core-shell nanostructures for biomedical
      applications. 

PMID- 25072519
TI  - Blood compatibility comparison for polysulfone membranes modified by grafting
      block and random zwitterionic copolymers via surface-initiated ATRP.
AB  - For blood-contacting materials, good blood compatibility, especially good
      anticoagulant property is of great importance. Zwitterionic polymers have been
      proved to be resistant to nonspecific protein adsorption and platelet adhesion;
      however, their anticoagulant property is always inadequate. In this study, two
      kinds of zwitterionic copolymers (sulfobetaine methacrylate and sodium p-styrene
      sulfonate random copolymer and block copolymer) with sulfonic groups were
      covalently grafted from polysulfone (PSf) membranes via surface-initiated atom
      transfer radical polymerization (SI-ATRP) to improve blood compatibility. Field
      emission scanning electron microscopy (FE-SEM), attenuated total reflectance
      Fourier transform infrared spectra (ATR-FTIR), X-ray photoelectron spectroscopy
      (XPS), and static water contact angle (WCA) were applied to characterize the
      morphologies, chemical compositions and hydrophilicity of the modified membranes.
      All the zwitterionic copolymer modified membranes showed improved blood
      compatibility, especially the anticoagulant property was obviously enhanced
      compared to the pristine PSf and simple zwitterionic polymer modified membranes.
      We also found that the random copolymer modified membranes showed better
      resistance to platelet adhesion than the block copolymer modified membranes. The
      zwitterionic copolymer modified membranes with integrated antifouling property
      and blood compatibility provided wide choice for specific applications such as
      hemodialysis, hemofiltration, and plasma separation. 

PMID- 25072521
TI  - Analysis of selected and designed chimeric D- and L-alpha-helix assemblies.
AB  - D-peptides have been attributed pharmacological advantages over regular L
      peptides, yet design rules are largely unknown. Based on a designed coiled coil
      like D/L heterotetramer, named L-Base/D-Acid, we generated a library offering
      alternative residues for interaction with the D-peptide. Phage display selection
      yielded one predominant peptide, named HelixA, that differed at 13 positions from
      the scaffold helix. In addition to the observed D-/L-heterotetramers, ratio
      dependent intermediate states were detected by isothermal titration calorimetry.
      Importantly, the formation of the selected HelixA/D-Acid bundle passes through
      fewer intermediate states than L-Base/D-Acid. Back mutation of HelixA core
      residues to L-Base (HelixLL) revealed that the residues at e/g-positions are
      responsible for the different intermediates. Furthermore, a Val-core variant
      (PeptideVV) was completely devoid of binding D-Acid, whereas an Ile-core helix
      (HelixII) interacted with D-Acid in a significantly more specific complex than L
      Base.

PMID- 25072520
TI  - Temporally-patterned deep brain stimulation in a mouse model of multiple
      traumatic brain injury.
AB  - We report that mice with closed-head multiple traumatic brain injury (TBI) show a
      decrease in the motoric aspects of generalized arousal, as measured by automated,
      quantitative behavioral assays. Further, we found that temporally-patterned deep
      brain stimulation (DBS) can increase generalized arousal and spontaneous motor
      activity in this mouse model of TBI. This arousal increase is input-pattern
      dependent, as changing the temporal pattern of DBS can modulate its effect on
      motor activity. Finally, an extensive examination of mouse behavioral capacities,
      looking for deficits in this model of TBI, suggest that the strongest effects of
      TBI in this model are found in the initiation of any kind of movement. 

PMID- 25072523
TI  - Qualitative analysis of a controlled trial of qigong for fibromyalgia: advancing
      understanding of an emerging health practice.
AB  - OBJECTIVES: A randomized controlled trial (RCT) and an extension trial of qigong
      (Chaoyi Fanhuan qigong [CFQ]) in patients with fibromyalgia were recently
      completed. In the present study, a qualitative analysis of comments from the RCT
      was undertaken using motivation and amount of practice to determine whether
      initial experiences provided information relevant to outcomes. INTERVENTION:
      Participants in the RCT received instruction in qigong (level 1 CFQ), practiced
      45 min/day for 8 weeks and continued practice to 6 months; open-ended qualitative
      comments on experiences were invited at 8 weeks and 4 and 6 months. Extension
      trial participants received further instruction (level 2 CFQ) and practiced
      regularly for 8 weeks-6 months. Comments from the original RCT were considered as
      narratives for the extension trial subgroup (n=20) and thematically, according to
      amount of practice, for all participants who completed the RCT (n=73). RESULTS:
      Narrative comments from the RCT for those who completed the extension trial
      (n=13) and those who withdrew from that trial (n=7) were considered separately.
      Participants reporting benefits within the first 8 weeks were more likely to
      maintain practice and report continued benefits at 4-6 months than those who
      withdrew from the trial. Thematic comments for all who completed the RCT (n=73)
      were considered in relation to amount of practice (per protocol, intermediate,
      minimal). Participants who practiced per protocol during the initial 8 weeks (>=5
      hours/wk) were more likely to maintain practice over 4-6 months and to report
      beneficial health effects from qigong. CONCLUSIONS: This retrospective
      qualitative analysis of information collected in an RCT of qigong for
      fibromyalgia indicates that favorable initial experiences with the practice over
      8 weeks predispose to continued practice and more health effects. Future
      individual trials and meta-analyses of qigong will need to attend to the amount,
      and potentially quality, of practice undertaken in considering trial outcomes.

PMID- 25072522
TI  - Differing effects when using phenylephrine and norepinephrine to augment cerebral
      blood flow after traumatic brain injury in the immature brain.
AB  - Low cerebral blood flow (CBF) states have been demonstrated in children early
      after traumatic brain injury (TBI), and have been correlated with poorer
      outcomes. Cerebral perfusion pressure (CPP) support following severe TBI is
      commonly implemented to correct cerebral hypoperfusion, but the efficacy of
      various vasopressors has not been determined. Sixteen 4-week-old female swine
      underwent nonimpact inertial brain injury in the sagittal plane. Intraparenchymal
      monitors were placed to measure intracranial pressure (ICP), CBF, brain tissue
      oxygen tension (PbtO2), and cerebral microdialysis 30 min to 6 h post-injury. One
      hour after injury, animals were randomized to receive either phenylephrine (PE)
      or norepinephrine (NE) infusions titrated to a CPP>70 mm Hg for 5 h. Animals were
      euthanized 6 h post-TBI, and brains were fixed and stained to assess regions of
      cell and axonal injury. After initiation of CPP augmentation with NE or PE
      infusions, there were no differences in ICP between the groups or over time.
      Animals receiving NE had higher PbtO2 than those receiving PE (29.6+/-10.2 vs.
      19.6+/-6.4 torr at 6 h post-injury, p<0.05). CBF increased similarly in both the
      NE and PE groups. CPP support with PE resulted in a greater reduction in
      metabolic crisis than with NE (lactate/pyruvate ratio 16.7+/-2.4 vs. 42.7+/-10.2
      at 6 h post-injury, p<0.05). Augmentation of CPP to 70 mm Hg with PE resulted in
      significantly smaller cell injury volumes at 6 h post-injury than CPP support
      with NE (0.4% vs. 1.4%, p<0.05). Despite similar increases in CBF, CPP support
      with NE resulted in greater brain tissue oxygenation and hypoxic-ischemic injury
      than CPP support with PE. Future clinical studies comparing the effectiveness of
      various vasopressors for CPP support are warranted.

PMID- 25072524
TI  - Incidence of deep vein thrombosis and thrombosis of the portal-mesenteric axis
      after laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Venous thromboembolism is the most common postoperative medical
      complication after bariatric surgery. Mortality associated with thromboembolic
      processes can reach up to 50%-75%. The aim of this study was to determine the
      incidence of deep vein thrombosis (DVT) and portal-splenic-mesenteric vein
      thrombosis (PSMVT) in our population undergoing laparoscopic sleeve gastrectomy
      (LSG) as the bariatric technique, with an anti-thromboembolic dosage scheme of
      0.5 mg/kg/day 12 hours preoperatively and maintained during 30 days
      postoperatively. PATIENTS AND METHODS: A prospective observational study was
      performed, including 100 consecutive patients undergoing LSG between October 2007
      and September 2013. To determine the incidence of DVT and PSMVT, all patients
      undergo contrast-enhanced abdominal computed tomography (CT) and Doppler
      ultrasonography (US) of both lower limbs on the third postoperative month,
      whether they were asymptomatic or symptomatic. RESULTS: Contrast-enhanced CT
      showed 1 case of PSMVT (1%). Two patients presented DVT in the right leg (2%).
      All the cases were asymptomatic. CONCLUSIONS: The incidence of PSMVT and DVT
      after LSG with a prophylactic low-molecular-weight heparin dose of 0.5 mg/kg/day
      and maintained during 30 days postoperatively is 1% and 2%, respectively.
      According to these results, a postoperative screening with Doppler US and/or
      contrast-enhanced CT seems to be unnecessary.

PMID- 25072525
TI  - Modulating short wavelength fluorescence with long wavelength light.
AB  - Two molecules in which the intensity of shorter-wavelength fluorescence from a
      strong fluorophore is modulated by longer-wavelength irradiation of an attached
      merocyanine-spirooxazine reverse photochromic moiety have been synthesized and
      studied. This unusual fluorescence behavior is the result of quenching of
      fluorophore fluorescence by the thermally stable, open, zwitterionic form of the
      spirooxazine, whereas the photogenerated closed, spirocyclic form has no effect
      on the fluorophore excited state. The population ratio of the closed and open
      forms of the spirooxazine is controlled by the intensity of the longer-wavelength
      modulated light. Both square wave and sine wave modulation were investigated.
      Because the merocyanine-spirooxazine is an unusual reverse photochrome with a
      thermally stable long-wavelength absorbing form and a short-wavelength absorbing
      photogenerated isomer with a very short lifetime, this phenomenon does not
      require irradiation of the molecules with potentially damaging ultraviolet light,
      and rapid modulation of fluorescence is possible. Molecules demonstrating these
      properties may be useful in fluorescent probes, as their use can discriminate
      between probe fluorescence and various types of adventitious "autofluorescence"
      from other molecules in the system being studied. 

PMID- 25072526
TI  - Role of Methoprene-tolerant (Met) in adult morphogenesis and in adult ecdysis of
      Blattella germanica.
AB  - Juvenile Hormone (JH) represses metamorphosis of young instars in insects. One of
      the main players in hormonal signalling is Methoprene-tolerant (Met), which plays
      the role of JH receptor. Using the Polyneopteran insect Blattella germanica as
      the model and RNAi for transcript depletion, we have confirmed that Met
      transduces the antimetamorphic signal of JH in young nymphs and plays a role in
      the last nymphal instar moult in this species. Previously, the function of Met as
      the JH receptor had been demonstrated in the Eumetabola clade, with experiments
      in Holometabola (in the beetle Tribolium castaneum) and in their sister group
      Paraneoptera (in the bug Pyrrhocoris apterus). Our result shows that the function
      of Met as JH receptor is also conserved in the more basal Polyneoptera. The
      function of Met as JH transducer might thus predate the evolutionary innovation
      of metamorphosis. Moreover, expression of Met was also found in last nymphal
      instar of B. germanica, when JH is absent. Depletion of Met in this stage
      provoked deficiencies in wing growth and ecdysis problems in the imaginal moult.
      Down-regulation of the ecdysone-inducible gene E75A and Insulin-Like-Peptide 1 in
      these Met-depleted specimens suggest that Met is involved in the ecdysone and
      insulin signalling pathways in last nymphal instar, when JH is virtually absent. 

PMID- 25072527
TI  - Clinical follow-up of horses treated with allogeneic equine mesenchymal stem
      cells derived from umbilical cord blood for different tendon and ligament
      disorders.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) offer promise as therapeutic aids in
      the repair of tendon and ligament disorders in sport horses. Equine allogeneic
      MSCs derived from umbilical cord blood (eUCB-MSCs) can be obtained in a minimally
      invasive fashion with successful propagation of MSCs. OBJECTIVE: The objective of
      this study was to determine the applicability and therapeutic effect of eUCB-MSCs
      on tendinitis of the superficial digital flexor tendon, desmitis of the
      suspensory ligament, tendinitis of the deep digital flexor tendon, and desmitis
      of the inferior check ligament in clinical cases. METHODS: A retrospective
      clinical study was performed. At two equine clinics, 52 warmblood horses were
      treated with cultured eUCB-MSCs between 2009 and 2012. About 2-10 * 10(6) cells
      per lesion were administered. When a lesion was treated twice, the total amount
      could run up to 20 * 10(6) cells. Pearson's chi-squared test was used to compare
      the effect of the injured structure on the success rate, as well as the effect of
      the age of the horse. RESULTS: Based on repeated examinations, 40 horses (77%)
      returned to work on the same or a higher level based on information provided by
      the owner. Neither the injured structure nor the age of the horse had a
      statistically significant influence on the result. CONCLUSION: Overall, the
      results of treatment of some tendon and ligament injuries with eUCB-MSCs in
      clinical cases are promising.

PMID- 25072529
TI  - The efficacy of capacitive radio-frequency diathermy in reducing buttock and
      posterior thigh cellulite measured through the cellulite severity scale.
AB  - BACKGROUND: Cellulite, despite its high prevalence in women, has been subjected
      to very little research, while the majority has been carried out using
      unvalidated evaluation tools. OBJECTIVES: To determine the efficacy of capacitive
      radio-frequency diathermy (CRFD) in reducing buttock and posterior thigh
      cellulite and to verify its relationship with the reduction of body weight.
      METHODS: Design: Experimental clinical study consists of two parallel groups.
      SAMPLE: Totally 54 lower limbs of 27 women (26.41 +/- 6.16 years) were considered
      with each patient's two limbs being assigned one to each group via simple random
      distribution. First group received local application of CRFD (30 min) and the
      second received the same treatment followed by a supplementary whole-segment
      application of CRFD (20 min). Each limb received 20 sessions, twice a week.
      VARIABLES: Cellulite Severity Scale dimensions score, weight and Body Mass Index
      (BMI) were taken for the evaluation of the study. RESULTS: A significance of p
      less than 0.01 was observed for all the variables in both groups, thereby
      demonstrating the effectiveness of both the treatments; no significant
      differences were observed between groups (p > 0.05). CONCLUSIONS: Monopolar
      static application of CRFD is effective in reducing buttock and posterior thigh
      cellulite. It appears that there is not necessarily any relationship between
      weight loss, decreased BMI and reduction in cellulite.

PMID- 25072530
TI  - Analytical method for the determination of trace toxic elements in milk based on
      combining Fe3O4 nanoparticles accelerated UV fenton-like digestion and solid
      phase extraction.
AB  - A UV Fenton-like digestion method was developed first time for a complete
      digestion of milk samples by using 1.6 g L(-1) Fe3O4 magnetic nanoparticles, 0.2%
      (v/v) nitric acid, and 6% (w/w) H2O2. During the digestion, the liberated As-, Sb
      , and Bi-containing species were preconcentrated onto the surface of Fe3O4
      magnetic nanoparticles, which were conveniently separated with a hand-held magnet
      and subsequently dissolved in hydrochloric acid prior to hydride generation
      atomic fluorescence spectrometric detection. Owing to the integration of UV
      Fenton-like digestion, solid phase extraction, and magnetic separation into a
      single step, the developed method significantly simplifies sample preparation
      steps and reduces chemical consumption and hazardous waste. Limits of detection
      of 0.0015, 0.0022, and 0.0025 MUg L(-1) were obtained for As, Sb, and Bi,
      respectively, using a 50 mL milk sample. The method was applied to the
      determination of these elements in a Certified Reference Material and milk
      samples. 

PMID- 25072531
TI  - Where does medical education stand in nurturing the 3Rs in medical students:
      responsibility, resilience and resolve?
AB  - Over the past decade, the medical education literature has recognized the need to
      develop a culture that nurtures wellbeing and resilience in students. However,
      the introduction of or increase in student fees precipitated a shift in higher
      education policies toward a consumer model of education. Importantly, it has
      altered the expectations of students and promoted a sense of "entitlement",
      rather than "striving" for something where success is not guaranteed. This model
      is consistent with materialism and status, and removed from intrinsic goals that
      are associated with mental and physical wellbeing. This article challenges
      medical educators to reconsider the current context of student learning and
      realign it with the graduate attributes needed to be a competent and responsible
      medical practitioner by enabling students to develop the 3Rs of resilience,
      responsibility and resolve. We propose that brave decisions and actions must be
      made by medical educators to provide students with opportunities to learn
      independence, self-management, and self-regulation and guarantee their role in
      helping medical students become resilient and responsible doctors of tomorrow.

PMID- 25072532
TI  - Thiocyanate complexes of uranium in multiple oxidation states: a combined
      structural, magnetic, spectroscopic, spectroelectrochemical, and theoretical
      study.
AB  - A comprehensive study of the complexes A4[U(NCS)8] (A = Cs, Et4N, (n)Bu4N) and
      A3[UO2(NCS)5] (A = Cs, Et4N) is described, with the crystal structures of
      [(n)Bu4N]4[U(NCS)8].2MeCN and Cs3[UO2(NCS)5].O0.5 reported. The magnetic
      properties of square antiprismatic Cs4[U(NCS)8] and cubic [Et4N]4[U(NCS)8] have
      been probed by SQUID magnetometry. The geometry has an important impact on the
      low-temperature magnetic moments: at 2 K, MUeff = 1.21 MUB and 0.53 MUB,
      respectively. Electronic absorption and photoluminescence spectra of the
      uranium(IV) compounds have been measured. The redox chemistry of [Et4N]4[U(NCS)8]
      has been explored using IR and UV-vis spectroelectrochemical methods. Reversible
      1-electron oxidation of one of the coordinated thiocyanate ligands occurs at
      +0.22 V vs Fc/Fc(+), followed by an irreversible oxidation to form dithiocyanogen
      (NCS)2 which upon back reduction regenerates thiocyanate anions coordinating to
      UO2(2+). NBO calculations agree with the experimental spectra, suggesting that
      the initial electron loss of [U(NCS)8](4-) is delocalized over all NCS(-)
      ligands. Reduction of the uranyl(VI) complex [Et4N]3[UO2(NCS)5] to uranyl(V) is
      accompanied by immediate disproportionation and has only been studied by DFT
      methods. The bonding in [An(NCS)8](4-) (An = Th, U) and [UO2(NCS)5](3-) has been
      explored by a combination of DFT and QTAIM analysis, and the U-N bonds are
      predominantly ionic, with the uranyl(V) species more ionic that the uranyl(VI)
      ion. Additionally, the U(IV)-NCS ion is more ionic than what was found for U(IV)
      Cl complexes. 

PMID- 25072533
TI  - The value of online learning and MRI: finding a niche for expensive technologies.
AB  - BACKGROUND: The benefits of online learning come at a price. How can we optimize
      the overall value? AIMS: Critically appraise the value of online learning.
      METHODS: Narrative review. RESULTS: Several prevalent myths overinflate the value
      of online learning. These include that online learning is cheap and easy (it is
      usually more expensive), that it is more efficient (efficiency depends on the
      instructional design, not the modality), that it will transform education
      (fundamental learning principles have not changed), and that the Net Generation
      expects it (there is no evidence of pent-up demand). However, online learning
      does add real value by enhancing flexibility, control and analytics. Costs may
      also go down if disruptive innovations (e.g. low-cost, low-tech, but
      instructionally sound "good enough" online learning) supplant technically
      superior but more expensive online learning products. Cost-lowering strategies
      include focusing on core principles of learning rather than technologies, using
      easy-to-learn authoring tools, repurposing content (organizing and sequencing
      existing resources rather than creating new content) and using course templates.
      CONCLUSIONS: Online learning represents just one tool in an educator's toolbox,
      as does the MRI for clinicians. We need to use the right tool(s) for the right
      learner at the right dose, time and route.

PMID- 25072534
TI  - Reactions of zirconium amide amidinates with dioxygen. Observation of an unusual
      peroxo intermediate in the formation of oxo compounds.
AB  - Reaction of d(0) Zr(NMe2)2[MeC(N(i)Pr)2]2 (1) with O2 at -30  degrees C gives
      three Zr containing products: a peroxo trimer {(MU-eta(2):eta(2)
      O2)Zr[MeC(N(i)Pr)2]2}3 (2), an oxo dimer {(MU-O)Zr[MeC(N(i)Pr)2]2}2 (3), and an
      oxo polymer {(MU-O)Zr[MeC(N(i)Pr)2]2}n (4). is a rarely observed peroxo complex
      from the reaction of a d(0) complex with O2.

PMID- 25072535
TI  - Successful anesthesia and hip surgery in a 107-year-old patient.
AB  - PATIENT: Female, 107. FINAL DIAGNOSIS: Hip fracture. SYMPTOMS: -. MEDICATION: -.
      CLINICAL PROCEDURE: Hip surgery. SPECIALTY: Orthopedics and Traumatology.
      OBJECTIVE: Rare disease. BACKGROUND: In modern societies, elderly populations
      have increased over the last four decades and have become the main clients of
      medical services. A hip fracture is a significant injury for anyone, but for
      older people it can be catastrophic. CASE REPORT: A 107-year-old female was
      admitted with fracture of the right hip. The patient took a single 200 mL
      carbohydrate drink orally two hours before surgery. Before induction of spinal
      anesthesia, routine monitoring was started and an intravenous line was placed.
      Crystalloids and hydroxyethyl starch in 0.9% sodium chloride solution were
      administered intravenously during the operation. After sedation with i.v.
      ketamine and midazolam, spinal puncture was performed with the patient in the
      sitting position and isobaric bupivacaine were administered. The level of sensory
      block was observed in T12 and motor blockade (grade 3) of the lower limbs. The
      surgical procedure lasted 60 minutes without hypotension, bradycardia or
      decreased oxygen saturation. For safety reason, the patient was transferred to
      the ICU for monitoring; intravenous hydration was withdrawn and released oral
      feeding six hours after the end of surgery. The patient was sent to his residence
      on the morning of the second day. CONCLUSIONS: This case showed that with
      suitable techniques and conduits can perform surgery in a patient with 107 years.

PMID- 25072528
TI  - Thrombolysis for acute ischaemic stroke.
AB  - BACKGROUND: Most strokes are due to blockage of an artery in the brain by a blood
      clot. Prompt treatment with thrombolytic drugs can restore blood flow before
      major brain damage has occurred and improve recovery after stroke in some people.
      Thrombolytic drugs, however, can also cause serious bleeding in the brain, which
      can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is
      licensed for use in selected patients within 4.5 hours of stroke in Europe and
      within three hours in the USA. There is an upper age limit of 80 years in some
      countries, and a limitation to mainly non-severe stroke in others. Forty per cent
      more data are available since this review was last updated in 2009. OBJECTIVES:
      To determine whether, and in what circumstances, thrombolytic therapy might be an
      effective and safe treatment for acute ischaemic stroke. SEARCH METHODS: We
      searched the Cochrane Stroke Group Trials Register (last searched November 2013),
      MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013). We also
      handsearched conference proceedings and journals, searched reference lists and
      contacted pharmaceutical companies and trialists. SELECTION CRITERIA: Randomised
      trials of any thrombolytic agent compared with control in people with definite
      ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors applied the
      inclusion criteria, extracted data and assessed trial quality. We verified the
      extracted data with investigators of all major trials, obtaining additional
      unpublished data if available. MAIN RESULTS: We included 27 trials, involving
      10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro
      urokinase or desmoteplase. Four trials used intra-arterial administration, while
      the rest used the intravenous route. Most data come from trials that started
      treatment up to six hours after stroke. About 44% of the trials (about 70% of the
      participants) were testing intravenous rt-PA. In earlier studies very few of the
      participants (0.5%) were aged over 80 years; in this update, 16% of participants
      are over 80 years of age due to the inclusion of IST-3 (53% of participants in
      this trial were aged over 80 years). Trials published more recently utilised
      computerised randomisation, so there are less likely to be baseline imbalances
      than in previous versions of the review. More than 50% of trials fulfilled
      criteria for high-grade concealment; there were few losses to follow-up for the
      main outcomes.Thrombolytic therapy, mostly administered up to six hours after
      ischaemic stroke, significantly reduced the proportion of participants who were
      dead or dependent (modified Rankin 3 to 6) at three to six months after stroke
      (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78 to 0.93). Thrombolytic
      therapy increased the risk of symptomatic intracranial haemorrhage (OR 3.75, 95%
      CI 3.11 to 4.51), early death (OR 1.69, 95% CI 1.44 to 1.98; 13 trials, 7458
      participants) and death by three to six months after stroke (OR 1.18, 95% CI 1.06
      to 1.30). Early death after thrombolysis was mostly attributable to intracranial
      haemorrhage. Treatment within three hours of stroke was more effective in
      reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79) without any increase
      in death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, 2187 participants). There was
      heterogeneity between the trials. Contemporaneous antithrombotic drugs increased
      the risk of death. Trials testing rt-PA showed a significant reduction in death
      or dependency with treatment up to six hours (OR 0.84, 95% CI 0.77 to 0.93, P =
      0.0006; 8 trials, 6729 participants) with significant heterogeneity; treatment
      within three hours was more beneficial (OR 0.65, 95% CI 0.54 to 0.80, P < 0.0001;
      6 trials, 1779 participants) without heterogeneity. Participants aged over 80
      years benefited equally to those aged under 80 years, particularly if treated
      within three hours of stroke. AUTHORS' CONCLUSIONS: Thrombolytic therapy given up
      to six hours after stroke reduces the proportion of dead or dependent people.
      Those treated within the first three hours derive substantially more benefit than
      with later treatment. This overall benefit was apparent despite an increase in
      symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at
      final follow-up (except for trials testing rt-PA, which had no effect on death at
      final follow-up). Further trials are needed to identify the latest time window,
      whether people with mild stroke benefit from thrombolysis, to find ways of
      reducing symptomatic intracranial haemorrhage and deaths, and to identify the
      environment in which thrombolysis may best be given in routine practice.

PMID- 25072536
TI  - Molecular cloning of peroxinectin gene and its expression in response to
      peptidoglycan and Vibrio harveyi in Indian white shrimp Fenneropenaeus indicus.
AB  - The cDNA sequence of peroxinectin was obtained from the haemocytes of Indian
      white shrimp Fenneropenaeus indicus using RT-PCR and RACE. Fenneropenaeus indicus
      peroxinectin (Fi-Pxn) sequence has an open reading frame (ORF) of 2415 bp
      encoding a protein of 804 amino acids with 21 residues signal sequence. The
      mature protein has molecular mass of 89.8 kDa with an estimated pI of 8.6. Two
      putative integrin-binding motifs, RGD and KGD, were observed at the basic N
      terminal and C-terminal part of the mature aminoacid sequence. Fi-Pxn nucleotide
      sequence comparison showed high homology to mud crab Scylla serrata (89%) and to
      various vertebrate and invertebrate species. qRT-PCR showed peroxinectin mRNA
      transcript in haemocytes of F. indicus increased at 6 h post injection of
      peptidoglycan and Vibrio harveyi. The Fi-Pxn was mainly expressed in the tissues
      of haemocytes and the heart. The moulting stage responses showed Fi-Pxn
      expression in premoult stages D0/1 and D0/2.

PMID- 25072540
TI  - [To explain is to narrate. How to visualize scientific data].
AB  - When you try to appeal a vast ranging audience, as it occurs at the New Scientist
      that addresses scientists as well as the general public, your scientific visual
      explainer must be succinct, clear, accurate and easily understandable. In order
      to reach this goal, your message should provide only the main data, the ones that
      allow you to balance information and clarity: information should be put into
      context and all the extra details should be cut down. It is very important, then,
      to know well both your audience and the subject you are going to describe, as
      graphic masters of the past, like William Playfair and Charles Minard, have
      taught us. Moreover, you should try to engage your reader connecting the
      storytelling power of words and the driving force of the graphics: colours,
      visual elements, typography. To be effective, in fact, an infographic should not
      only be truthful and functional, but also elegant, having style and legibility. 

PMID- 25072538
TI  - Generalized linear mixed model analysis of risk factors for contamination of
      moisture-enhanced pork with Campylobacter jejuni and Salmonella enterica
      Typhimurium.
AB  - Translocation of foodborne pathogens into the interior tissues of pork through
      moisture enhancement may be of concern if the meat is undercooked. In the present
      study, a five-strain mixture of Campylobacter jejuni or Salmonella enterica
      Typhimurium was evenly spread on the surface of fresh pork loins. Pork loins were
      injected, sliced, vacuum packaged, and stored. After storage, sliced pork was
      cooked by traditional grilling. Survival of Salmonella Typhimurium and C. jejuni
      in the interior tissues of the samples were analyzed by enumeration. The
      populations of these pathogens dropped below the detection limit (10 colony
      forming units/g) in most samples that were cooked to 71.1 degrees C or above. The
      general linear mixed model procedure was used to model the association between
      risk factors and the presence/absence of these pathogens after cooking. Estimated
      regression coefficients associated with the fixed effects indicated that the
      recovery probability of Salmonella Typhimurium was negatively associated with
      increasing level of enhancement. The effects of moisture enhancement and cooking
      on the recovery probability of C. jejuni were moderated by storage temperature.
      Our findings will assist food processors and regulatory agencies with science
      based evaluation of the current processing, storage condition, and cooking
      guideline for moisture-enhanced pork.

PMID- 25072537
TI  - Proline-rich region of non-muscle myosin light chain kinase modulates kinase
      activity and endothelial cytoskeletal dynamics.
AB  - Disruption of the pulmonary endothelial barrier and subsequent vascular leak is a
      hallmark of acute lung injury. Dynamic rearrangements in the endothelial cell
      (EC) peripheral membrane and underlying cytoskeleton are critical determinants of
      barrier function. The cytoskeletal effector protein non-muscle myosin light chain
      kinase (nmMLCK) and the actin-binding regulatory protein cortactin are important
      regulators of the endothelial barrier. In the present study we functionally
      characterize a proline-rich region of nmMLCK previously identified as the
      possible site of interaction between nmMLCK and cortactin. A mutant nmMLCK
      construct deficient in proline residues at the putative sites of cortactin
      binding (amino acids 973, 976, 1019, 1022) was generated. Co-immunoprecipitation
      studies in human lung EC transfected with wild-type or mutant nmMLCK demonstrated
      similar levels of cortactin interaction at baseline and after stimulation with
      the barrier-enhancing agonist, sphingosine 1-phosphate (S1P). In contrast,
      binding studies utilizing recombinant nmMLCK fragments containing the wild-type
      or proline-deficient sequence demonstrated a two-fold increase in cortactin
      binding (p<0.01) to the mutant construct. Immunofluorescent microscopy revealed
      an increased stress fiber density in ECs expressing GFP-labeled mutant nmMLCK at
      baseline (p=0.02) and after thrombin (p=0.01) or S1P (p=0.02) when compared to
      wild-type. Mutant nmMLCK demonstrated an increase in kinase activity in response
      to thrombin (p<0.01). Kymographic analysis demonstrated an increased EC membrane
      retraction distance and velocity (p<0.01) in response to the barrier disrupting
      agent thrombin in cells expressing the mutant vs. the wild-type nmMLCK construct.
      These results provide evidence that critical prolines within nmMLCK (amino acids
      973, 976, 1019, 1022) regulate cytoskeletal and membrane events associated with
      pulmonary endothelial barrier function. 

PMID- 25072541
TI  - [Safety in surgery].
AB  - The effectiveness of the World Health Organization's (WHO) surgical safety
      checklist (SSCL) in decreasing mortality and morbidity of surgical procedures was
      firstly suggested in 2009; the checklist is now strongly recommended
      internationally for adoption as a highly effective yet economically simple
      intervention. However, since 2009 several published studies have reported
      inconsistent results, besides many issues concerning local implementation.
      Drawing on the recently published experience carried out in Ontario, a concise
      overview of the current debate is presented, with some comments on implications
      for the national healthcare system in Italy. More generally, the need to include
      the implementation of the SSCL in a larger effort addressing safety in surgery is
      pointed out. 

PMID- 25072542
TI  - [Burnout syndrome in pre-hospital and hospital emergency. Cognitive study in two
      cohorts of nurses].
AB  - INTRODUCTION: Burnout syndrome (BOS) associated with stress has been documented
      in health care professionals in many specialties. The emergency department and
      the pre-hospital healthcare services are highly stressful environments. Little is
      known about the BOS in critical care nursing staff. The objective of the study is
      to compare the incidence of BOS and its three domains, namely, emotional
      exhaustion, depersonalization and reduced professional accomplishment, in two
      cohorts of critical care nurses: a pre-hospital and a hospital emergency service.
      METHODS: A survey using a questionnaire (the Maslach Burnout Inventory-General
      Survey, MBI-GS), among nurses of two Italian emergency services has been
      performed: a hospital emergency service (HES, Emergency Department or "Pronto
      Soccorso") and a pre-hospital emergency service (PHES, territorial healthcare
      service or "Centrale Operativa 118"). RESULTS: All 60 nurses surveyed (82%
      female) filled the questionnaires. BOS-related symptoms have been identified in
      at least 50% of the nurses in the HES: 50% suffered a medium-high emotional
      exhaustion, 75% had a medium-high depersonalization and 92.5% had a medium-high
      reduced professional accomplishment. Among the PEHS nurses, BOS-related symptoms
      have been identified in at least 60% of the respondents: 60% had a medium-high
      emotional exhaustion, 70% had a medium-high depersonalization and 95% had a
      medium-high reduced professional accomplishment. Moreover, the likelihood that a
      nurse has a severe BOS, that is at least one degree of high burnout or >=2
      degrees of medium burnout, is significantly higher in the group of the PHES than
      in the HES (90% vs 60%, p <0.02). CONCLUSION: At least two-thirds of critical
      care nursing staff had a severe BOS. The incidence of BOS appeared to be similar
      among PHES and HES nurses with a higher trend for the former. Further
      interventional studies are needed to investigate the determinants of BOS among
      critical care nurses and the potentially preventive strategies.

PMID- 25072543
TI  - [Support to spiritual needs in hospital care. Integration perspective in modern
      hospitals].
AB  - Within the course of medical care in the most advanced health care settings, an
      increasing attention is being paid to the so-called care humanization. According
      to this perspective, we try to integrate the usual care pathways with aspects
      related to the spiritual and religious dimension of all people and their
      families, as well as the employees themselves. It is clearly important to
      establish this kind of practices on the basis of scientific evidences. That is
      the reason why it's a necessity to improve the knowledge about the importance
      that spiritual assistance can offer within the current health service. The aim of
      this work is to show the relevance of the integration of spiritual perspectives
      in the hospital setting according to a multidisciplinary point of view. In this
      work many data that emerge from the international scientific literature, as well
      as the definition that is given to the concept of "spirituality" are analyzed;
      about this definition in fact there is not unanimous consent even today. It is
      also analyzed the legal situation in force within the European territory
      according to the different laws and social realities. Finally, the possible
      organizational practices related to spiritual support are described and the
      opportunity to specific accreditation pathways and careful training of chaplains
      able to integrate traditional religious practices with modern spiritual
      perspectives is discussed. 

PMID- 25072544
TI  - [Metabolic therapy for heart failure].
AB  - Heart failure may promote metabolic changes such as insulin resistance, in part
      through neurohumoral activation, and determining an increased utilization of non
      carbohydrate substrates for energy production. In fact, fasting blood ketone
      bodies as well as fat oxidation have been shown to be increased in patients with
      heart failure. The result is depletion of myocardial ATP, phosphocreatine and
      creatine kinase with decreased efficiency of mechanical work. A direct approach
      to manipulate cardiac energy metabolism consists in modifying substrate
      utilization by the failing heart. To date, the most effective metabolic
      treatments include several pharmacological agents that directly inhibit fatty
      acid oxidation. The results of current research are supporting the concept that
      shifting the energy substrate preference away from fatty acid metabolism and
      toward glucose metabolism could be an effective adjunctive treatment in patients
      with heart failure. Trimetazidine is the most studied drug in this context.
      Several small studies have evidenced the usefulness of such additional
      therapeutic tools for heart failure. More specifically, recent meta-analyses and
      a multicenter retrospective study have shown that additional use of trimetazidine
      in patients with heart failure, along with symptoms and cardiac function
      improvement, also provides a significant protective effect on all-cause
      mortality, cardiovascular events and hospitalization due to cardiac causes.
      Nevertheless, the exact role of metabolic therapy in heart failure is yet to be
      established, and a large multicenter randomized trial is necessary. 

PMID- 25072545
TI  - [Diagnosing Alzheimer's disease: from research to clinical practice and ethics].
AB  - In 2011, the so-called Dubois criteria introduced the use of biomarkers in
      research (in particular, brain amyloid positron emission tomography imaging and
      the cerebrospinal fluid levels of tau/fosfo-tau and beta-amyloid 1-42) for the
      early or preclinical diagnosis of Alzheimer's disease. Even so, we are looking at
      an increased use of these markers in clinical practice. In the 1960s, Alzheimer's
      disease was considered a rare form of presenile dementia, but gradually it has
      been recognized as the prevalent form of old-age dementia. As a consequence, what
      was once regarded as an inevitable outcome of old age is now recognized as a true
      disease. Several factors contributed to this paradigm shift, in particular a
      longer lifespan, new techniques of in vivo study of the central nervous system,
      and the pressure exerted by the pharmaceutical industry and patient groups. The
      current lack of disease-modifying therapies and the high incidence of mild
      cognitive impairment, which is a risk factor for dementia, raise a series of
      clinical ethical problems ranging from how diagnosis is communicated to how
      resources are used. This article offers a conceptual scheme through which these
      issues can be addressed. 

PMID- 25072546
TI  - [The Health Technology Assessment Engine of the Academic Hospital of Udine: first
      appraisal].
AB  - The Health Technology Assessment Engine (HTAE) of the Academic Hospital of Udine
      aggregates about one hundred of health technology assessment websites. It was
      born thanks to Google technology in 2008 and after about four years of testing it
      became public for everybody from the Homepage of the Italian Society of Health
      Technology Assessment (SIHTA). In this paper the first results obtained with this
      resource are reported. The role of the scientific librarian is examined not only
      as a support specialist in bibliographic search but also as a creative expert in
      managing new technologies for the community. 

PMID- 25072547
TI  - [Sometimes they come back! A case of Shoshin Beriberi in Northern Italy (2012)].
AB  - A 78-year-old man presented to the emergency department with symptoms and signs
      suggestive of heart failure. Only after a long interview we discovered that the
      patient has been eating, for over 20 years, only chestnut honey and chestnut jam
      produced by himself. He refused any other foods, because of the fear of being
      poisoned; he did not drink alcohol at all. The clinical picture was attributable
      to Beriberi, and the patient recovered promptly after treatment with thiamine. A
      high clinical suspicion and an early thiamine supplementation might shorten the
      duration of work-up and hospital length of stay, as well as prevent extensive and
      expensive diagnostic work-up, thus simplifying the clinical management. 

PMID- 25072550
TI  - The impracticality of biomedical rejuvenation therapies: translational and
      pharmacological barriers.
AB  - The notion that it is possible to eradicate age-related degeneration and live a
      life with a negligible rate of senescence solely by using a physical "repair
      oriented" approach is flawed on a number of fronts. Here, I will argue that there
      are so many unknown variables embedded in this line of thinking that make the
      final result impossible to predict. Two relatively easy-to-research areas are the
      search for successful cross-link breakers and an effective lysosomal degradation
      therapy. A more complex and speculative strategy is whole-body interdiction of
      lengthening of telomeres (WILT). Highlighting these as examples, I argue that it
      is unlikely that such rejuvenation biotechnologies will be used meaningfully by
      the general public. The discussion assumes that although such therapies may in
      theory one day be developed in the laboratory, and even possibly be formulated as
      physical clinical therapies, these will be unusable in practical terms when
      applied upon humans at large. Due to inherent characteristics of our biological,
      evolutionary, and psychological heritage, it is implausible that curing aging
      will occur by using physical interventions alone.

PMID- 25072551
TI  - Cupriavidus pauculus bacteremia in a child on extracorporeal membrane
      oxygenation.
AB  - We report a case of bacteremia secondary to Cupriavidus pauculus in a 15-month
      old boy on extracorporeal membrane oxygenation (ECMO). The source of the organism
      was water in the thermoregulator reservoir. The child responded well to cefepime
      and ciprofloxacin, a delayed oxygenator change out and replacement of the
      thermoregulator reservoir with a unit that was cleaned and decontaminated with
      sodium hypochlorite. Isolation of Cupriavidus pauculus from a patient on ECMO
      support should raise suspicion of the reservoir as a source. 

PMID- 25072552
TI  - Modified HeartMate II driveline externalization technique significantly decreases
      incidence of infection and improves long-term survival.
AB  - Driveline (DL) infection has been a major source of morbidity and mortality
      following HeartMate II left ventricular assist device (LVAD) implant, despite a
      significantly lower incidence compared with pulsatile flow devices. The purpose
      of this study was to compare the incidence of DL infection using two different
      externalization techniques. Between July 1, 2008, and October 15, 2011, 125
      consecutive patients underwent HeartMate II LVAD implant at a single institution.
      Patients that underwent implant in 2008-2009 (n = 45) had the velour portion of
      the DL externalized (Velour group) and those that were implanted in 2010-2011 (n
      = 80) had only the silicone portion externalized (Silicone group). Kaplan-Meier
      analysis with log-rank test was used to compare actuarial DL infection-free
      survival and a composite of death and DL infection-free survival. There were
      20/45 (44.4%) DL infections in the Velour group compared with 7/80 (8.8%) in the
      Silicone group. Driveline infection-free survival was significantly better for
      the Silicone versus Velour group as was the composite end-point of death and
      infection-free survival (p < 0.001). Externalization of only the silicone portion
      of the DL led to a dramatic reduction in infections and significantly improved
      survival after implant. This represents an opportunity to decrease the incidence
      of this important cause of morbidity and mortality after LVAD implant. 

PMID- 25072553
TI  - Bivalirudin for treatment of LVAD thrombosis: a case series.
AB  - Both platelet- and fibrin-rich thrombi have been described in patients with pump
      thrombosis associated with continuous flow left ventricular assist devices
      (LVADs). Bivalirudin is a direct thrombin inhibitor that also inhibits platelet
      adhesion. Compared to heparin, this hirudin analog is less immunogenic, binds to
      both free- and clot-bound fibrin, and has a lower risk of major bleeding. In a
      recently published algorithm on the step-wise approach to the diagnosis and
      management of LVAD thrombosis, direct thrombin inhibitors were included as a
      treatment option in the setting of persistent hemolysis, power spikes, and heart
      failure symptoms. Evidence to support the use of a direct thrombin inhibitor for
      LVAD thrombosis is limited and anecdotal. We describe the first case series to
      date of the use of bivalirudin as an alternative to heparin in six
      hemodynamically stable patients with a total of ten hospitalizations for
      HeartMate II LVAD thrombosis. 

PMID- 25072554
TI  - Extracorporeal membrane oxygenation with subclavian artery cannulation in awake
      patients with pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is a challenging disease process to manage.
      Respiratory and hemodynamic changes that accompany general anesthesia lead to a
      significant risk of cardiovascular collapse. Certain cases of decompensated PH
      require extracorporeal membrane oxygenation (ECMO) support as either a bridge to
      lung transplantation or bridge to recovery. Performing ECMO cannulation without
      intubation or general anesthesia in these patients may be safer given the
      severity of their underlying disease process. We present three cases of upper
      body ECMO cannulation performed on patients with pulmonary hypertension while
      awake and without mechanical ventilation. 

PMID- 25072555
TI  - Robotic-assisted implantation of ventricular assist device after sternectomy and
      pectoralis muscle flap.
AB  - Left ventricular assist devices are increasingly important in the management of
      advanced heart failure. Most patients who benefit from these devices have had
      some prior cardiac surgery, making implantation of higher risk. This is
      especially true in patients who have had prior pectoralis flap reconstruction
      after sternectomy for mediastinitis. We outline the course of such a patient, in
      whom the use of robotic assistance allowed for a less invasive device
      implantation approach with preservation of the flap for transplantation. 

PMID- 25072556
TI  - Photocarrier relaxation pathway in two-dimensional semiconducting transition
      metal dichalcogenides.
AB  - Two-dimensional crystals of semiconducting transition metal dichalcogenides
      absorb a large fraction of incident photons in the visible frequencies despite
      being atomically thin. It has been suggested that the strong absorption is due to
      the parallel band or 'band nesting' effect and corresponding divergence in the
      joint density of states. Here, we use photoluminescence excitation spectroscopy
      to show that the band nesting in mono- and bilayer MX2 (M=Mo, W and X=S, Se)
      results in excitation-dependent characteristic relaxation pathways of the
      photoexcited carriers. Our experimental and simulation results reveal that
      photoexcited electron-hole pairs in the nesting region spontaneously separate in
      k-space, relaxing towards immediate band extrema with opposite momentum. These
      effects imply that the loss of photocarriers due to direct exciton recombination
      is temporarily suppressed for excitation in resonance with band nesting. Our
      findings highlight the potential for efficient hot carrier collection using these
      materials as the absorbers in optoelectronic devices. 

PMID- 25072557
TI  - Academic Medicine. Foreword.

PMID- 25072558
TI  - A systems approach to implementation of eLearning in medical education: five MEPI
      schools' journeys.
AB  - How should eLearning be implemented in resource-constrained settings? The
      introduction of eLearning at four African medical schools and one school of
      pharmacy, all part of the Medical Education Partnership Initiative (MEPI)
      eLearning Technical Working Group, highlighted the need for five factors
      essential for successful and sustainable implementation: institutional support;
      faculty engagement; student engagement; technical expertise; and infrastructure
      and support systems. All five MEPI schools reported strengthening technical
      expertise, infrastructure, and support systems; four schools indicated that they
      were also successful in developing student engagement; and three reported making
      good progress in building institutional support. Faculty engagement was the one
      core component that all five schools needed to enhance. 

PMID- 25072559
TI  - Building surgical research capacity in Mozambique.

PMID- 25072560
TI  - Using virtual microscopy at Copperbelt University, Zambia.

PMID- 25072561
TI  - Challenges and opportunities for new medical schools in Africa: the Consortium of
      New Southern African Medical Schools (CONSAMS).

PMID- 25072562
TI  - Strengthening health systems by integrating health care, medical education, and
      research: University of Nairobi experience.

PMID- 25072563
TI  - A brief history of medical education in Sub-Saharan Africa.
AB  - Developments in medical education in Sub-Saharan Africa over the past 100 years
      have been characterized by the continent's unique history. During the first half
      of the 20th century, the Europeans effectively installed medical education in
      their African colonies. The years 1950 to 1960 were distinguished by successful
      movements for independence, with new governments giving priority to medical
      education. By 1980, there were 51 medical schools in Sub-Saharan Africa. The
      period from 1975 to 1990 was problematic both politically and economically for
      Sub-Saharan Africa, and medical schools did not escape the general difficulties.
      War, corruption, mounting national debts, and political instability were
      characteristics of this period. In many countries, maintaining medical school
      assets--faculty members, buildings, laboratories, libraries--became difficult,
      and emigration became the goal of many health professionals. In contrast, the
      past 20 years have seen rapid growth in the number of medical schools in Sub
      Saharan Africa. Economic growth and political stability in most Sub-Saharan
      African countries augur well for investment in health systems strengthening and
      in medical education. There are, nonetheless, major problem areas, including
      inadequate funding, challenges of sustainability, and the continuing brain drain.
      The 20th century was a time of colonialism and the struggle for independence
      during which medical education did not advance as quickly or broadly as it did in
      other regions of the world. The 21st century promises a different history, one of
      rapid growth in medical education, leading to better care and better health for
      the people of Africa.

PMID- 25072564
TI  - Evolution of a Multiuniversity Monitoring and Evaluation Technical Working Group.

PMID- 25072565
TI  - The Ghana Emergency Medicine Collaborative.

PMID- 25072566
TI  - Developing a medical school psychiatry training program in Botswana: overcoming
      obstacles with innovation.

PMID- 25072567
TI  - Graduate tracking systems for the medical schools in Africa: processes for
      developing an implementation framework.

PMID- 25072568
TI  - Cancer service delivery in Malawi: impact of a MEPI pilot award.

PMID- 25072569
TI  - The contribution of the Medical Education Partnership Initiative to Africa's
      renewal.
AB  - African countries gained independence from colonialism five decades ago with high
      expectations. Initial positive achievements were not sustained, however, and the
      continent slumped on many fronts. Medical schools were not spared: Many declined,
      became inward looking, and suffered from massive migration of health
      professionals to richer countries, commonly known as "brain drain." For more than
      a decade, however, Africa has been experiencing a renewal, backed by a more
      accountable African Union and a strong global movement for equity and social
      justice. The Medical Education Partnership Initiative (MEPI), a $130-million, 5
      year award to 13 African medical schools by the U.S. government, arrived at an
      opportune time and is poised to contribute to Africa's transformation, provided
      that it continues to focus on capacity building, locally relevant research,
      retention, sustainability, and strengthening of health systems. MEPI also needs
      to distill and share its many successes with country governments and join
      existing regional and global health workforce institutions to reach African
      leaders at all levels. MEPI will represent another legacy of support to Africa,
      similar to the taming of the HIV pandemic but on a bigger scale of catalyzing the
      creation of a new generation of transformative African leaders. 

PMID- 25072570
TI  - Growing partnerships: leveraging the power of collaboration through the Medical
      Education Partnership Initiative.
AB  - A major goal of the Medical Education Partnership Initiative (MEPI) is to improve
      local health systems by strengthening medical education in Sub-Saharan Africa. A
      new approach to collaboration was intended to overcome the one-sided nature of
      many partnerships that often provide more rewards to institutions from wealthy
      countries than to their Sub-Saharan African counterparts. The benefits of this
      MEPI approach are reflected in at least five positive outcomes. First, effective
      partnerships have been developed across a diverse group of MEPI stakeholders.
      Second, a "community of practice" has been established to continue strengthening
      medical education in Sub-Saharan Africa. Third, links have been strengthened
      among MEPI health science schools in Sub-Saharan Africa, their communities, and
      ministries of both health and education. Fourth, respect among partners in the
      United States for a culture of ownership and self-determinism among their African
      counterparts committed to improving education has been enhanced. And finally,
      performance metrics for strengthening of health science education in Sub-Saharan
      Africa have been advanced. Meanwhile, partner medical schools in the United
      States have witnessed the benefits of collaborating across traditional
      disciplinary boundaries, such as physicians working within highly functioning
      community-based health care teams with many of the participating schools in Sub
      Saharan Africa. MEPI demonstrates that North-South as well as South-South
      partnerships, with an explicit focus on improving local health systems through
      better education, can be designed to empower partners in the South with support
      from collaborators in the North. 

PMID- 25072571
TI  - The Nursing Education Partnership Initiative (NEPI): innovations in nursing and
      midwifery education.
AB  - The nursing and midwifery workforce is key to improving the performance of the
      health system overall. Health workforce shortages are significantly influenced by
      the productive capacity of health professions education institutions. Long
      standing underinvestment in preservice nursing and midwifery education severely
      limits the capacity of institutions to educate nurses and midwives in sufficient
      numbers, and with the necessary clinical skills, for current and anticipated
      population health needs. The Nursing Education Partnership Initiative (NEPI) was
      established in 2011 by the U.S. President's Emergency Plan for AIDS Relief in
      response to key capacity-building challenges facing preservice nursing and
      midwifery education in Sub-Saharan Africa. NEPI has formed partnerships with
      governments and key stakeholders in Ethiopia, Democratic Republic of Congo,
      Lesotho, Malawi, and Zambia and supports 19 nursing and midwifery education
      institutions and 1 nursing council. NEPI has been informed by activities that
      strengthen education systems, institutions, and organizations as well as faculty
      capacity building. Ministry of health-led advisory groups were established to
      provide strategic direction and oversight for the work, fostering intersectoral
      dialogue and ensuring country ownership and sustainability. Three illustrative
      examples of innovations at the system, institution, and workforce levels describe
      approaches for country ownership, for addressing the shortage of highly qualified
      faculty, and for remedying the inadequate teaching and learning infrastructure. 

PMID- 25072572
TI  - Redefining the measure of medical education: harnessing the transformative
      potential of MEPI.
AB  - The massive shortage of skilled health professionals in many parts of the world
      is a critical constraint to achieving the goal of universal health coverage. This
      shortfall reflects a generalized failure of leadership: a chronic misalignment
      between the direction of health professional education and the health goals of
      society. The Medical Education Partnership Initiative (MEPI) and Nurse Education
      Partnership Initiative (NEPI) are outliers in this regard through their
      deliberate efforts to revitalize education to address the pressing health needs
      of Sub-Saharan Africa. Inspired by this example, the World Bank Group sees health
      professional education institutions (HPEIs) as an insufficiently tapped source of
      knowledge and know-how for accelerating health achievement. The challenge ahead
      is to articulate clearer expectations for HPEI performance, marshal more and
      smarter investments across the public and private sectors, prioritize
      accountability, incentivize innovation, and strengthen global learning and
      evaluation. It is time to build on the positive legacy of MEPI/NEPI and ensure
      that the conditions are made available for a new generation of health workers
      with the competencies to meet the health and development challenges of today and
      tomorrow. 

PMID- 25072573
TI  - Academic Medicine. Preface.

PMID- 25072574
TI  - Implementation of the Medical Education Partnership Initiative: medical students'
      perspective.
AB  - The Medical Education Partnership Initiative (MEPI) is contributing to the
      transformation of medical training in Africa. In this paper, medical students
      present their perspective on how MEPI initiatives have influenced five key areas
      related to African medical trainees: educational infrastructure, information
      technology, community-based training, scientific research, and professional
      outlook and goals. They propose three new areas of focus that could further
      assist MEPI in bettering medical training in Africa. 

PMID- 25072575
TI  - Expanding clinical medical training opportunities at the University of Nairobi:
      adapting a regional medical education model from the WWAMI program at the
      University of Washington.
AB  - A major medical education need in Sub-Saharan Africa includes expanding clinical
      training opportunities to develop health professionals. Medical education
      expansion is a complicated process that requires significant investment of
      financial and human resources, but it can also provide opportunities for
      innovative approaches and partnerships. In 2010, the U.S. President's Emergency
      Plan for AIDS Relief launched the Medical Education Partnership Initiative to
      invest in medical education and health system strengthening in Africa. Building
      on a 30-year collaborative clinical and research training partnership, the
      University of Nairobi in Kenya developed a pilot regional medical education
      program modeled on the WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho)
      medical education program at the University of Washington in the United States.
      The University of Nairobi adapted key elements of the WWAMI model to expand
      clinical training opportunities without requiring major capital construction of
      new buildings or campuses. The pilot program provides short-term clinical
      training opportunities for undergraduate students and recruits and trains
      clinical faculty at 14 decentralized training sites. The adaptation of a model
      from the Northwestern United States to address medical education needs in Kenya
      is a successful transfer of knowledge and practices that can be scaled up and
      replicated across Sub-Saharan Africa. 

PMID- 25072576
TI  - Ethiopian medical schools' rapid scale-up to support the government's goal of
      universal coverage.
AB  - In 2003, Ethiopia declared it would pursue the goal of universal primary health
      coverage. In response to the critical shortage of human resources for health
      care, the government decided to rapidly increase the training of health workers
      to provide basic services, including health education, disease prevention, and
      family health services primarily to rural areas. This approach, which became
      known as the "flooding strategy," was extended in 2005 to include medical
      doctors. Between 2003 and 2009, the number of universities and health science
      colleges grew from 5 to 23, and the original 5 medical schools were given a
      mandate to increase their annual enrollment by three to four times. This article
      describes how the "flooding strategy" strained and threatened the quality of the
      Ethiopian medical education system and how Addis Ababa University responded by
      leveraging a timely grant through the Medical Education Partnership Initiative
      (MEPI) to support the establishment of a consortium of four Ethiopian medical
      schools (MEPI-E). The consortium goals are to address the new demands by (1)
      maintaining and improving the quality of education through innovation and
      efficient use of resources, (2) developing and implementing new strategies to
      build human capacity and promote faculty retention, and (3) increasing locally
      relevant research and bioethics capacity. Implementation of program began in May
      2011. Although it is still under way, MEPI-E has already catalyzed the
      development of a national network of medical schools, enabling unprecedented
      collaboration to respond to the increased demands on the Ethiopian medical
      education system. 

PMID- 25072577
TI  - Building communities of practice: MEPI creates a commons.
AB  - The Medical Education Partnership Initiative (MEPI) supports medical education
      capacity development, retention, and research in Sub-Saharan African
      institutions. Today, MEPI comprises more than 40 medical schools in Africa and 20
      in the United States. Since 2011, the MEPI Coordinating Center, working with the
      MEPI schools and the U.S. government, has laid the groundwork and served as a
      catalyst for the creation and development of MEPI "communities of practice"
      (CoPs). These CoPs encompass seven components, some of which are virtual while
      others are tangible. They include technical working groups, principal
      investigator site visit exchanges, an annual symposium, a MEPI journal
      supplement, the MEPI Web site, newsletters, and webinars. Despite certain
      challenges and the question of sustainability, the presence within the MEPI
      network of an organization focused on promoting group consciousness and
      facilitating collaborative projects is an asset that is likely to continue to pay
      dividends for the foreseeable future. 

PMID- 25072578
TI  - The Medical and Nursing Education Partnership Initiatives.
AB  - The Medical Education Partnership Initiative (MEPI) and Nursing Education
      Partnership Initiative (NEPI) are innovative approaches to strengthening the
      academic and clinical training of physicians and nurses in Sub-Saharan African
      countries, which are heavily burdened by HIV/AIDS. Begun in 2010 by the U.S.
      President's Emergency Plan for AIDS Relief with the National Institutes of
      Health, investments in curricula, innovative learning technologies, clinical
      mentoring, and research opportunities are providing a strong base to advance high
      quality education for growing numbers of urgently needed new physicians and
      nurses in these countries. The MEPI and NEPI focus on strengthening learning
      institutions is central to the vision for expanding the pool of health
      professionals to meet the full range of a country's health needs. A robust
      network of exchange between education institutions and training facilities, both
      within and across countries, is transforming the quality of medical education and
      augmenting a platform for research opportunities for faculty and clinicians,
      which also serves as an incentive to retain professionals in the country.
      Excellence in patient care and a spirit of professionalism, core to MEPI and
      NEPI, provide a strong foundation for the planning and delivery of health
      services in participating countries. 

PMID- 25072579
TI  - Community-based education programs in Africa: faculty experience within the
      Medical Education Partnership Initiative (MEPI) network.
AB  - PURPOSE: This paper examines the various models, challenges, and evaluative
      efforts of community-based education (CBE) programs at Medical Education
      Partnership Initiative (MEPI) schools and makes recommendations to strengthen
      those programs in the African context. METHODS: Data were gathered from 12 MEPI
      schools through self-completion of a standardized questionnaire on goals,
      activities, challenges, and evaluation of CBE programs over the study period,
      from November to December 2013. Data were analyzed manually through the collation
      of inputs from the schools included in the survey. RESULTS: CBE programs are a
      major component of the curricula of the surveyed schools. CBE experiences are
      used in sensitizing students to community health problems, attracting them to
      rural primary health care practice, and preparing them to perform effectively
      within health systems. All schools reported a number of challenges in meeting the
      demands of increased student enrollment. Planned strategies used to tackle these
      challenges include motivating faculty, deploying students across expanded
      centers, and adopting innovations. In most cases, evaluation of CBE was limited
      to assessment of student performance and program processes. CONCLUSIONS: Although
      the CBE programs have similar goals, their strategies for achieving these goals
      vary. To identify approaches that successfully address the challenges,
      particularly with increasing enrollment, medical schools need to develop
      structured models and tools for evaluating the processes, outcomes, and impacts
      of CBE programs. Such efforts should be accompanied by training faculty and
      embracing technology, improving curricula, and using global/regional networking
      opportunities.

PMID- 25072580
TI  - A strategy for developing future academic leaders for South Africa in a resource
      constrained environment.
AB  - A key challenge in addressing the shortage of health care workers in resource
      constrained environments is ensuring that there is optimal academic capacity for
      their training. South Africa's University of KwaZulu-Natal has placed academic
      and research capacity building at the heart of its program with the Medical
      Education Partnership Initiative in a program called ENhancing Training and
      REsearch capacity and Expertise (ENTREE). The program aims to increase the
      quantity, quality, and retention of health care graduates. It is premised on the
      basis that research capacity development will lead to an increase in teachers who
      will be essential to improving the quality and quantity of health care workers
      needed to meet South Africa's health challenges. This is being achieved through
      four components of the program: (1) infusion of the undergraduate program with
      research modules; (2) attraction of academically talented students in the middle
      of their undergraduate program into a parallel track that has research capacity
      as its major thrust; (3) attraction of qualified health care personnel into a
      supported PhD program; and (4) providing strong research ethics training and
      mentorship. A significant proportion of the program is being executed in rural
      training sites, to increase the probability that trainees will return to the
      sites as mentors. 

PMID- 25072581
TI  - Modernizing and transforming medical education at the Kilimanjaro Christian
      Medical University College.
AB  - The Kilimanjaro Christian Medical University (KCMU) College and the Medical
      Education Partnership Initiative (MEPI) are addressing the crisis in Tanzanian
      health care manpower by modernizing the college's medical education with new
      tools and techniques. With a $10 million MEPI grant and the participation of its
      partner, Duke University, KCMU is harnessing the power of information technology
      (IT) to upgrade tools for students and faculty. Initiatives in eLearning have
      included bringing fiber-optic connectivity to the campus, offering campus-wide
      wireless access, opening student and faculty computer laboratories, and providing
      computer tablets to all incoming medical students. Beyond IT, the college is also
      offering wet laboratory instruction for hands-on diagnostic skills, team-based
      learning, and clinical skills workshops. In addition, modern teaching tools and
      techniques address the challenges posed by increasing numbers of students. To
      provide incentives for instructors, a performance-based compensation plan and
      teaching awards have been established. Also for faculty, IT tools and training
      have been made available, and a medical education course management system is now
      being widely employed. Student and faculty responses have been favorable, and the
      rapid uptake of these interventions by students, faculty, and the college's
      administration suggests that the KCMU College MEPI approach has addressed unmet
      needs. This enabling environment has transformed the culture of learning and
      teaching at KCMU College, where a path to sustainability is now being pursued. 

PMID- 25072582
TI  - Medical Education for Equitable Services for All Ugandans (MESAU) consortium:
      development and achievements.
AB  - PURPOSE: In 2011, five medical schools in Uganda formed the Medical Education for
      Equitable Services for All Ugandans consortium to address the medical education
      challenges in meeting the nation's health needs. In this paper, the authors
      document the development and achievements of this unique collaboration to
      transform medical education in Uganda. METHOD: A longitudinal qualitative study
      employed anthropological techniques to examine the proposed idea and development
      of the consortium, the experiences of consortium members, and the successes and
      challenges encountered during its first three years (2011-2013). RESULTS: The
      consortium approach to medical education has made important contributions to
      member institutions despite initial reservations and uncertainties. Acceptance of
      the consortium emerged because of the added benefits accruing to individual
      institutions and the network. The consortium has flourished partly because of its
      organizational structure, the support of its leadership, the ownership and active
      participation by member institutions, and a strong commitment to its broader
      goals. However, some challenges in implementation remain, including inadequate
      capacity, limited grants management experience, and varying degrees of research
      expertise among the participating institutions. CONCLUSIONS: Despite these
      challenges, the consortium approach has had a positive impact on medical
      education by reducing interinstitutional rivalries, promoting strong
      collaboration, and providing mutual support and the sharing of resources for
      medical education and research in Uganda.

PMID- 25072583
TI  - Strengthening research governance for sustainable research: experiences from
      three Zimbabwean universities.
AB  - A robust research system requires a robust governance framework. As part of the
      Medical Education Partnership Initiative, three Zimbabwean universities partnered
      with two U.S. universities in a project to strengthen research governance in the
      Zimbabwean universities. The project aimed at (1) developing research policies,
      (2) strengthening central research management offices, (3) developing a research
      administration curriculum, and (4) enhancing awareness about the role and
      relevance of research administration in other universities and research
      institutions in Zimbabwe. Through the efforts of the partners, a generic research
      policy was developed and successfully adapted by the institutions. A curriculum
      was drafted, and module development experts are helping to finalize the
      curriculum to meet university requirements for accreditation of training research
      administrators. The Association of Research Managers of Zimbabwe was established
      to promote information sharing and professionalize research administration. The
      consortium approach enabled rapid and smooth development and adoption of research
      policies in the institutions. It also helped researchers and managers accept
      research administration as an essential structure and function. The experiences
      and lessons learned are reported here to benefit other institutions and
      consortia. 

PMID- 25072584
TI  - Guiding the development of family medicine training in Africa through
      collaboration with the Medical Education Partnership Initiative.
AB  - Africa's health care challenges include a high burden of disease, low life
      expectancy, health workforce shortages, and varying degrees of commitment to
      primary health care on the part of policy makers and government officials. One
      overarching goal of the Medical Education Partnership Initiative (MEPI) is to
      develop models of medical education in Sub-Saharan Africa. To do this, MEPI has
      created a network of universities and other institutions that, among other
      things, recognizes the importance of supporting training programs in family
      medicine. This article provides a framework for assessing the stage of the
      development of family medicine training in Africa, including the challenges that
      were encountered and how educational organizations can help to address them. A
      modified "stages of change" model (precontemplation, contemplation, action,
      maintenance, and relapse) was used as a conceptual framework to understand the
      various phases that countries go through in developing family medicine in the
      public sector and to determine the type of assistance that is useful at each
      phase. 

PMID- 25072585
TI  - Innovative strategies for transforming internal medicine residency training in
      resource-limited settings: the Mozambique experience.
AB  - With approximately 4 physicians per 100,000 inhabitants, Mozambique faces one of
      the most severe health care provider shortages in Sub-Saharan Africa. The lack of
      sufficient well-trained medical school faculty is one of Mozambique's major
      barrier to producing new physicians annually. A partnership between the
      Universidade Eduardo Mondlane and the University of California, San Diego, has
      addressed this challenge with support from the Medical Education Partnership
      Initiative. After an initial needs assessment involving questionnaires and focus
      groups of residents, and working with key members from the Ministry of Health,
      the Medical Council, and Maputo Central Hospital, a set of interventions was
      designed. The hospital's internal medicine residency program was chosen as the
      focus for the plan. Interventions included curriculum design, new teaching
      methodologies, investment in an informatics infrastructure for access to digital
      references, building capacity to support clinical research, and providing
      financial incentives to retain junior faculty. The number of candidates entering
      the internal medicine residency program has increased, and detailed monitoring
      and evaluation is measuring the impact of these changes on the quality of
      training. These changes are expected to improve the long-term quality of
      postgraduate training in general through dissemination to other departments. They
      also have the potential to facilitate equitable distribution of specialists
      nationwide by expanding postgraduate training to other hospitals and
      universities. 

PMID- 25072586
TI  - Transforming the health care workforce through partnerships.

PMID- 25072587
TI  - Establishing a new medical school: Botswana's experience.
AB  - Having adequate numbers of qualified human resources for health is essential for
      any effective health care system. However, there is a global shortage of skilled
      health care workers, especially in Sub-Saharan African countries. This shortage
      is exacerbated by a disproportionately high rate of infectious diseases, the
      burden of emerging chronic, noncommunicable diseases, and the emigration of
      medical doctors. Botswana has also experienced this critical shortage of doctors
      for many years. To address the shortage, the country in the 1990 s embarked on an
      aggressive program to train its students at foreign medical schools. Despite
      intensified training, many graduates have not returned. As a result, the country
      decided to establish a medical school within Botswana. The newly established
      school was awarded a grant from the Medical Education Partnership Initiative,
      which has helped to accelerate the school's development. This paper describes the
      authors' experiences, highlighting curriculum, staffing, infrastructure
      approaches, key successes, and challenges encountered. The paper concludes by
      proposing solutions. The authors' experiences and the lessons learned can inform
      colleagues in other countries considering similar endeavors.

PMID- 25072588
TI  - Innovations to enhance the quality of health professions education at the
      University of Zimbabwe College of Health Sciences--NECTAR program.
AB  - The University of Zimbabwe College of Health Sciences (UZCHS) is Zimbabwe's
      premier health professions training institution. However, several concerns were
      raised during the past decade over the quality of health education at UZCHS. The
      number of faculty and students declined markedly until 2010, when there was a
      medical student intake of 147 while the faculty comprised only 122 (39%) of a
      possible 314 positions. The economic and political crises that the country
      experienced from 1999 to 2009 compounded the difficulties faced by the
      institution by limiting the availability of resources. The Medical Education
      Partnership Initiative funding opportunity has given UZCHS the stimulus to embark
      on reforms to improve the quality of health education it offers. UZCHS, in
      partnership with the University of Colorado School of Medicine, the University of
      Colorado Denver Evaluation Center, and Stanford University, designed the Novel
      Education Clinical Trainees and Researchers (NECTAR) program to implement a
      series of health education innovations to meet this challenge. Between 2010 and
      2013, innovations that have positively affected the quality of health professions
      education at UZCHS include the launch of comprehensive faculty development
      programs and mentored clinical and research programs for postgraduate students. A
      competency-based curriculum reform process has been initiated, a health
      professions department has been established, and the Research Support Center has
      been strengthened, providing critical resources to institutionalize health
      education and research implementation at the college. A core group of faculty
      trained in medical education has been assembled, helping to ensure the
      sustainability of these NECTAR activities. 

PMID- 25072589
TI  - The importance of research in the MEPI program: perspectives from the National
      Institutes of Health.
AB  - The Medical Education Partnership Initiative (MEPI), which aims to strengthen and
      transform education in medicine and the health sciences in Africa, has placed
      special emphasis on including research as part of new curricula. The great
      progress achieved against HIV/AIDS globally has been based in part on major
      research conducted by African investigators working in African institutions at
      African field sites in collaboration with international partners. This experience
      demonstrates the key role of academic institutions in generating knowledge while
      training the next generation of health professionals. Research is a key driver of
      innovation in the health sciences, and it can spur global collaborations, build
      substantial financial support, empower scientific leadership, and promote
      economic development. Through MEPI, young investigators are becoming engaged in
      research training early in their careers with projects that develop research
      skills to help them better understand how to evaluate and integrate new evidence
      into policy and practice, advance the science of health within their countries,
      and strengthen the academic institutions in which they work. Research training is
      an essential component of MEPI and should endure long after the program ends. It
      may help build a critical mass of researchers as well as a cadre of health
      professionals, teachers, and leaders who will be better equipped to embrace the
      continually changing panorama of advances in the health sciences. 

PMID- 25072590
TI  - Enhancement of health research capacity in Nigeria through north-south and in
      country partnerships.
AB  - Research productivity in Sub-Saharan Africa has the potential to affect teaching,
      student quality, faculty career development, and translational country-relevant
      research as it has in developed countries. Nigeria is the most populous country
      in Africa, with an academic infrastructure that includes 129 universities and 45
      medical schools; however, despite the size, the country has unacceptably poor
      health status indicators. To further develop the research infrastructure in
      Nigeria, faculty and research career development topics were identified within
      the six Nigerian universities of the nine institutions of the Medical Education
      Partnership Initiative in Nigeria (MEPIN) consortium. The consortium identified a
      training model that incorporated multi-institutional "train-the-trainers"
      programs at the University of Ibadan, followed by replication at the other MEPIN
      universities. More than 140 in-country trainers subsequently presented nine
      courses to more than 1,600 faculty, graduate students, and resident doctors
      throughout the consortium during the program's first three years (2011-2013).
      This model has fostered a new era of collaboration among the major Nigerian
      research universities, which now have increased capacity for collaborative
      research initiatives and improved research output. These changes, in turn, have
      the potential to improve the nation's health outcomes.

PMID- 25072591
TI  - Strengthening faculty recruitment for health professions training in basic
      sciences in Zambia.
AB  - Zambia is facing a crisis in its human resources for health, with deficits in the
      number and skill mix of health workers. The University of Zambia School of
      Medicine (UNZA SOM) was the only medical school in the country for decades, but
      recently it was joined by three new medical schools--two private and one public.
      In addition to expanding medical education, the government has also approved
      several allied health programs, including pharmacy, physiotherapy, biomedical
      sciences, and environmental health. This expansion has been constrained by
      insufficient numbers of faculty. Through a grant from the Medical Education
      Partnership Initiative (MEPI), UNZA SOM has been investing in ways to address
      faculty recruitment, training, and retention. The MEPI-funded strategy involves
      directly sponsoring a cohort of faculty at UNZA SOM during the five-year grant,
      as well as establishing more than a dozen new master's programs, with the goal
      that all sponsored faculty are locally trained and retained. Because the issue of
      limited basic science faculty plagues medical schools throughout Sub-Saharan
      Africa, this strategy of using seed funding to build sustainable local capacity
      to recruit, train, and retain faculty could be a model for the region.

PMID- 25072592
TI  - A halogenophilic pathway in the reactions of transition metal carbonyl anions
      with [(eta6-iodobenzene)Cr(CO)3].
AB  - The paper provides the first example of formal nucleophilic substitution by the
      halogenophilic pathway in Cr(CO)3 complexes of haloarenes with metal carbonyl
      anions. All metal carbonyl anions examined attack [(eta(6)-iodobenzene)Cr(CO)3]
      at halogen, which is shown by aryl carbanion scavenging with t-BuOH. The reaction
      with K[CpFe(CO)2] gives only the dehalogenated arene, but the reaction with
      K[Cp*Fe(CO)2] (Cp* = eta(5)-C5Me5) results in nucleophilic substitution to give
      [(eta(6)-C6H5FeCp*(CO)2)Cr(CO)3]. Reaction with Na[Re(CO)5] quantitatively gives
      the iodo(acyl)rhenate anion Na[(eta(6)-C6H5C(O)ReI(CO)4)Cr(CO)3] and in the case
      of K[Mn(CO)5] a mixture of sigma-aryl complexes [(eta(6)-C6H5Mn(CO)5)Cr(CO)3] and
      K[(eta(6)-C6H5Mn(CO)4I)Cr(CO)3]. An analogous rhenium complex Na[(eta(6)
      C6H5Re(CO)4I)Cr(CO)3] is formed from the initial iodo(acyl)rhenate upon prolonged
      standing at 20  degrees C, and its structure (in the form of [NEt4](+) salt) is
      established by X-ray diffraction analysis. The reaction of [(eta(6)
      chlorobenzene)Cr(CO)3] with K[CpFe(CO)2], in contrast, proceeds by the common
      S(N)2Ar mechanism.

PMID- 25072593
TI  - Antagonistic and synergistic effects of light irradiation on the effects of
      copper on Chlamydomonas reinhardtii.
AB  - The present study showed the important role of light intensity and spectral
      composition on Cu uptake and effects on green alga Chlamydomonas reinhardtii.
      High-intenisty light (HL) increased cellular Cu concentrations, but mitigated the
      Cu-induced decrease in chlorophyll fluorescence, oxidative stress and lipid
      peroxidation at high Cu concentrations, indicating that Cu and HL interact in an
      antagonistic manner. HL up-regulated the transcription of genes involved in the
      antioxidant response in C. reinhardtii and thus reduced the oxidative stress upon
      exposure to Cu and HL. Combined exposure to Cu and UVBR resulted in an increase
      of cellular Cu contents and caused severe oxidative damage to the cells. The
      observed effects were higher than the sum of the effects corresponding to
      exposure to UVBR or Cu alone suggesting a synergistic interaction. 

PMID- 25072595
TI  - The effect of a connexin43-based Peptide on the healing of chronic venous leg
      ulcers: a multicenter, randomized trial.
AB  - The gap junction protein, connexin43 (Cx43), has critical roles in the
      inflammatory, edematous, and fibrotic processes following dermal injury and
      during wound healing, and is abnormally upregulated at the epidermal wound
      margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic
      of the carboxyl-terminus of Cx43, accelerates fibroblast migration and
      proliferation, and wound reepithelialization. In a prospective, multicenter
      clinical trial conducted in India, adults with chronic VLUs were randomized to
      treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC)
      protocols, involving maintaining wound moisture and four-layer compression
      bandage therapy, or SOC protocols alone. The primary end point was mean percent
      ulcer reepithelialization from baseline to 12 weeks. A significantly greater
      reduction in mean percent ulcer area from baseline to 12 weeks was associated
      with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with
      compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of
      secondary efficacy end points indicated a reduced median time to 50 and 100%
      ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC
      protocols may represent a well-tolerated, highly effective therapeutic strategy
      that expedites chronic venous ulcer healing by treating the underlying ulcer
      pathophysiology through Cx43-mediated pathways. 

PMID- 25072596
TI  - The infection biology of Sphaerulina musiva: clues to understanding a forest
      pathogen.
AB  - Trees in the genus Populus and their interspecific hybrids are used across North
      America for fiber production and as a potential source of biofuel. Plantations of
      these species are severely impacted by a fungal pathogen, Sphaerulina musiva, the
      cause of leaf spot and stem canker. An inoculation protocol that does not rely on
      stem wounding to achieve infection was recently developed. Using this protocol
      two experiments were conducted to examine infection biology and disease
      development in the S. musiva-Populus interaction. In the first experiment non
      wounded stems of one moderately resistant clone (NM6) and one susceptible clone
      (NC11505) were inoculated and examined by scanning electron microscopy at six
      different times (6 h, 12 h, 24 h, 72 h, 1 week, and 3 weeks) post-inoculation.
      The images indicate that the pathogen appears to enter host tissue through small
      openings and lenticels and that there are no significant differences in the
      penetration rate between the moderately resistant (NM6) and susceptible (NC11505)
      clones at 12 h post-inoculation. In a second experiment a histological comparison
      of stem cankers for resistant clone DN74 and susceptible clone NC11505 were
      conducted at three time points (3 weeks, 5 weeks, and 7 weeks) post-inoculation.
      Distinct differences in disease development were apparent between the resistant
      and susceptible clones at each time point, with the susceptible clone exhibiting
      a weak and delayed defense response. These results suggest, that following
      penetration, the pathogen may be able to interfere with the defense response in
      the susceptible host. 

PMID- 25072597
TI  - Capsaicin induces "brite" phenotype in differentiating 3T3-L1 preadipocytes.
AB  - OBJECTIVE: Targeting the energy storing white adipose tissue (WAT) by
      pharmacological and dietary means in order to promote its conversion to energy
      expending "brite" cell type holds promise as an anti-obesity approach. Present
      study was designed to investigate/revisit the effect of capsaicin on adipogenic
      differentiation with special reference to induction of "brite" phenotype during
      differentiation of 3T3-L1 preadipocytes. METHODS: Multiple techniques such as
      Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and
      matured adipocytes have been employed to understand the effect of capsaicin at
      different doses. In addition to in-vitro experiments, in-vivo studies were
      carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a
      TRPV1 agonist) and in mice administered capsaicin. RESULTS: TRPV1 channels are
      expressed in preadipocytes but not in adipocytes. In preadipocytes, both
      capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This
      stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses,
      capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while
      at higher doses it enhances accumulation of lipids and suppresses expression of
      its receptor. In doses of 0.1-100 uM, capsaicin promotes expression of major pro
      adipogenic factor PPARgamma and some of its downstream targets. In concentrations
      of 1 uM, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin
      treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in
      increased expression of brown fat cell marker genes. In white adipose of mice,
      capsaicin administration leads to increase in browning-specific genes. Global
      TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor
      activity with no change in body weight. CONCLUSION: Our findings suggest the dual
      modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in
      3T3-L1 via TRPV1 activation and induces brown-like phenotype whereas higher
      doses.

PMID- 25072598
TI  - Demonstrating the use of high-volume electronic medical claims data to monitor
      local and regional influenza activity in the US.
AB  - INTRODUCTION: Fine-grained influenza surveillance data are lacking in the US,
      hampering our ability to monitor disease spread at a local scale. Here we
      evaluate the performances of high-volume electronic medical claims data to assess
      local and regional influenza activity. MATERIAL AND METHODS: We used electronic
      medical claims data compiled by IMS Health in 480 US locations to create weekly
      regional influenza-like-illness (ILI) time series during 2003-2010. IMS Health
      captured 62% of US outpatient visits in 2009. We studied the performances of IMS
      ILI indicators against reference influenza surveillance datasets, including CDC
      ILI outpatient and laboratory-confirmed influenza data. We estimated correlation
      in weekly incidences, peak timing and seasonal intensity across datasets,
      stratified by 10 regions and four age groups (<5, 5-29, 30-59, and 60+ years). To
      test IMS-Health performances at the city level, we compared IMS-ILI indicators to
      syndromic surveillance data for New York City. We also used control data on
      laboratory-confirmed Respiratory Syncytial Virus (RSV) activity to test the
      specificity of IMS-ILI for influenza surveillance. RESULTS: Regional IMS-ILI
      indicators were highly synchronous with CDC's reference influenza surveillance
      data (Pearson correlation coefficients rho>=0.89; range across regions, 0.80
      0.97, P<0.001). Seasonal intensity estimates were weakly correlated across
      datasets in all age data (rho<=0.52), moderately correlated among adults
      (rho>=0.64) and uncorrelated among school-age children. IMS-ILI indicators were
      more correlated with reference influenza data than control RSV indicators (rho =
      0.93 with influenza v. rho = 0.33 with RSV, P<0.05). City-level IMS-ILI
      indicators were highly consistent with reference syndromic data (rho>=0.86).
      CONCLUSION: Medical claims-based ILI indicators accurately capture weekly
      fluctuations in influenza activity in all US regions during inter-pandemic and
      pandemic seasons, and can be broken down by age groups and fine geographical
      areas. Medical claims data provide more reliable and fine-grained indicators of
      influenza activity than other high-volume electronic algorithms and should be
      used to augment existing influenza surveillance systems.

PMID- 25072599
TI  - Strain-engineered manufacturing of freeform carbon nanotube microstructures.
AB  - The skins of many plants and animals have intricate microscale surface features
      that give rise to properties such as directed water repellency and adhesion,
      camouflage, and resistance to fouling. However, engineered mimicry of these
      designs has been restrained by the limited capabilities of top-down fabrication
      processes. Here we demonstrate a new technique for scalable manufacturing of
      freeform microstructures via strain-engineered growth of aligned carbon nanotubes
      (CNTs). Offset patterning of the CNT growth catalyst is used to locally modulate
      the CNT growth rate. This causes the CNTs to collectively bend during growth,
      with exceptional uniformity over large areas. The final shape of the curved CNT
      microstructures can be designed via finite element modeling, and compound
      catalyst shapes produce microstructures with multidirectional curvature and
      unusual self-organized patterns. Conformal coating of the CNTs enables tuning of
      the mechanical properties independently from the microstructure geometry,
      representing a versatile principle for design and manufacturing of complex
      microstructured surfaces. 

PMID- 25072600
TI  - Effects of water molecules on rearrangements of formamide on the kaolinite basal
      (001) surface.
AB  - The effects of kaolinite mineral surfaces on the unimolecular rearrangements of
      formamide (FM) were investigated using periodic density functional theory in
      conjunction with pseudopotential plane-wave approach. Surface hydroxyl groups
      covering the octahedral surface of kaolinite were found to play the role of
      catalysts in the transformations of FM. They induce a reduction of 31 kcal/mol on
      the energy barrier for formation of its isomer aminohydroxymethylene (AHM), which
      is close to the reduction amount calculated for water-catalyzed reactions. This
      suggests that the kaolinite octahedral surface exerts a catalytic effect similar
      to that of the water molecule. As the tetrahedral surface does not contain
      catalytic surface hydroxyl groups, only water-assisted FM transformation was
      therefore studied on this surface whose energy barrier amounts to ~17 kcal/mol.
      The combined effect of both water and kaolinite on FM rearrangements via triple
      hydrogen transfer reactions does not significantly lower the energy barriers, as
      compared to those of double hydrogen transfer reactions. The triple hydrogen
      transfer energy barriers amount to ~20 and ~36 kcal/mol, and the double ones are
      ~21 and ~40 kcal/mol for formation of formimic acid and AHM isomers,
      respectively. However, the energies of the systems in water-catalyzed channels
      lie below the available energies of the original reactants, and thus these
      channels are more favored than the water-free ones. With its multiple functions
      as both a supporting plate-form and a catalyst for FM reactions, kaolinite can
      thus be regarded as an important natural catalyst for prebiotic synthesis. 

PMID- 25072602
TI  - Hydrogen-atom abstraction from a model amino acid: dependence on the attacking
      radical.
AB  - We have used computational chemistry to examine the reactivity of a model amino
      acid toward hydrogen abstraction by HO*, HOO*, and Br*. The trends in the
      calculated condensed-phase (acetic acid) free energy barriers are in accord with
      experimental relative reactivities. Our calculations suggest that HO* is likely
      to be the abstracting species for reactions with hydrogen peroxide. For HO*
      abstractions, the barriers decrease as the site of reaction becomes more remote
      from the electron-withdrawing alpha-substituents, in accord with a diminishing
      polar deactivating effect. We find that the transition structures for alpha- and
      beta-abstractions have additional hydrogen-bonding interactions, which lead to
      lower gas-phase vibrationless electronic barriers at these positions. Such
      favorable interactions become less important in a polar solvent such as acetic
      acid, and this leads to larger calculated barriers when the effect of solvation
      is taken into account. For Br* abstractions, the alpha-barrier is the smallest
      while the beta-barrier is the largest, with the barrier gradually becoming
      smaller further along the side chain. We attribute the low barrier for the alpha
      abstraction in this case to the partial reflection of the thermodynamic effect of
      the captodatively stabilized alpha-radical product in the more product-like
      transition structure, while the trend of decreasing barriers in the order beta >
      gamma > delta ~ epsilon is explained by the diminishing polar deactivating
      effect. More generally, the favorable influence of thermodynamic effects on the
      alpha-abstraction barrier is found to be smaller when the transition structure
      for hydrogen abstraction is earlier. 

PMID- 25072603
TI  - Use of the piggyBac transposon to create stable packaging cell lines for the
      production of clinical-grade self-inactivating gamma-retroviral vectors.
AB  - Efforts to improve the biosafety of gamma-retroviral-mediated gene therapy have
      resulted in a shift toward the use of self-inactivating (SIN) gamma-retroviral
      vectors. However, scale-up and manufacturing of such vectors requires significant
      optimization of transient transfection-based processes or development of novel
      platforms for the generation of stable producer cell clones. To that end, we
      describe the use of the piggybac transposon to generate stable producer cell
      clones for the production of SIN gamma-retroviral vectors. The piggybac
      transposon is a universal tool allowing for the stable integration of SIN gamma
      retroviral constructs into murine (PG13) and human 293-based Phoenix (GALV and
      RD114, respectively) packaging cell lines without reverse transcription.
      Following transposition, a high-titer clone is selected for manufacture of a
      master cell bank and subsequent gamma-retroviral vector supernatant production.
      Packaging cell clones created using the piggybac transposon have comparable
      titers to non-SIN vectors generated via conventional methods. We describe herein
      the use of the piggybac transposon for the production of stable packaging cell
      clones for the manufacture of clinical-grade SIN gamma-retroviral vectors for ex
      vivo gene therapy clinical trials.

PMID- 25072604
TI  - Stereoselective synthesis of O-tosyl azabicyclic derivatives via aza Prins
      reaction of endocyclic N-acyliminium ions: application to the total synthesis of
      (+/-)-epi-indolizidine 167B and 209D.
AB  - A diastereoselective protocol has been established for the synthesis of 4-O-tosyl
      piperidine containing hexahydroindolizin-3(2H)-one, hexahydro-1H-quinolizin-4(6H)
      one and 1,3,4,10b-tetrahydropyrido[2,1-a]isoindol-6(2H)-one derivatives via the
      aza-Prins cyclization reaction of cyclic N-acyliminium ions mediated by p-toluene
      sulphonic acid (p-TSA) under mild conditions. The reaction is highly
      diastereoselective and gives excellent yields. This method has been applied to an
      efficient total synthesis of indolizidine alkaloids, (+/-)-epi-indolizidine 167B
      and 209D. 

PMID- 25072605
TI  - Advances in in-situ product recovery (ISPR) in whole cell biotechnology during
      the last decade.
AB  - The review presents the state-of-the-art in the applications of in-situ product
      recovery (ISPR) in whole-cell biotechnology over the last 10years. It summarizes
      various ISPR-integrated fermentation processes for the production of a wide
      spectrum of bio-based products. A critical assessment of the performance of
      various ISPR concepts with respect to the degree of product enrichment, improved
      productivity, reduced process flows and increased yields is provided.
      Requirements to allow a successful industrial implementation of ISPR are also
      discussed. Finally, supporting technologies such as online monitoring,
      mathematical modeling and use of recombinant microorganisms with ISPR are
      presented. 

PMID- 25072606
TI  - Outlier removal and the relation with reporting errors and quality of
      psychological research.
AB  - BACKGROUND: The removal of outliers to acquire a significant result is a
      questionable research practice that appears to be commonly used in psychology. In
      this study, we investigated whether the removal of outliers in psychology papers
      is related to weaker evidence (against the null hypothesis of no effect), a
      higher prevalence of reporting errors, and smaller sample sizes in these papers
      compared to papers in the same journals that did not report the exclusion of
      outliers from the analyses. METHODS AND FINDINGS: We retrieved a total of 2667
      statistical results of null hypothesis significance tests from 153 articles in
      main psychology journals, and compared results from articles in which outliers
      were removed (N = 92) with results from articles that reported no exclusion of
      outliers (N = 61). We preregistered our hypotheses and methods and analyzed the
      data at the level of articles. Results show no significant difference between the
      two types of articles in median p value, sample sizes, or prevalence of all
      reporting errors, large reporting errors, and reporting errors that concerned the
      statistical significance. However, we did find a discrepancy between the reported
      degrees of freedom of t tests and the reported sample size in 41% of articles
      that did not report removal of any data values. This suggests common failure to
      report data exclusions (or missingness) in psychological articles. CONCLUSIONS:
      We failed to find that the removal of outliers from the analysis in psychological
      articles was related to weaker evidence (against the null hypothesis of no
      effect), sample size, or the prevalence of errors. However, our control sample
      might be contaminated due to nondisclosure of excluded values in articles that
      did not report exclusion of outliers. Results therefore highlight the importance
      of more transparent reporting of statistical analyses.

PMID- 25072607
TI  - End-stage kidney disease and kidney transplantation in HIV-positive patients: an
      observational cohort study.
AB  - End-stage kidney disease (ESKD) is a major complication of HIV infection. We
      observed a 3.8-fold increase in ESKD prevalence among black patients in the UK
      CHIC cohort during the 12-year study period. As of 2005, 107 patients had an ESKD
      diagnosis, 69 of whom (64%) were considered suitable for kidney transplantation
      (KT) and 34 (32%) had received a KT. Survival was similar for KT recipients and
      those awaiting KT (85% and 89% at 5 years, respectively; P = 0.53). Our results
      endorse the use of KT to manage ESKD in HIV-positive patients.

PMID- 25072609
TI  - Immunodeficiency at the start of combination antiretroviral therapy: steady
      improvement or step changes?

PMID- 25072608
TI  - Process monitoring of an HIV treatment as prevention program in British Columbia,
      Canada.
AB  - BACKGROUND: In light of accumulated scientific evidence of the secondary
      preventive benefits of antiretroviral therapy, a growing number of jurisdictions
      worldwide have formally started to implement HIV Treatment as Prevention (TasP)
      programs. To date, no gold standard for TasP program monitoring has been
      described. Here, we describe the design and methods applied to TasP program
      process monitoring in British Columbia (BC), Canada. METHODS: Monitoring
      indicators were selected through a collaborative and iterative process by an
      interdisciplinary team including representatives from all 5 regional health
      authorities, the BC Centre for Disease Control (BCCDC), and the BC Centre for
      Excellence in HIV/AIDS (BC-CfE). An initial set of 36 proposed indicators were
      considered for inclusion. These were ranked on the basis of 8 criteria: data
      quality, validity, scientific evidence, informative power of the indicator,
      feasibility, confidentiality, accuracy, and administrative requirement. The
      consolidated list of indicators was included in the final monitoring report,
      which was executed using linked population-level data. RESULTS: A total of 13
      monitoring indicators were included in the BC TasP Monitoring Report. Where
      appropriate, indicators were stratified by subgroups of interest, including HIV
      risk group and demographic characteristics. Six Monitoring Reports are generated
      quarterly: 1 for each of the regional health authorities and a consolidated
      provincial report. CONCLUSIONS: We have developed a comprehensive TasP process
      monitoring strategy using evidence-based HIV indicators derived from linked
      population-level data. Standardized longitudinal monitoring of TasP program
      initiatives is essential to optimize individual and public health outcomes and to
      enhance program efficiencies.

PMID- 25072610
TI  - Factors associated with CD8+ T-cell activation in HIV-1-infected patients on long
      term antiretroviral therapy.
AB  - BACKGROUND: Abnormal levels of CD8 T-cell activation persist in HIV-1-infected
      patients on suppressive antiretroviral therapy (ART) and may be deleterious.
      METHODS: CD8 T-cell activation (% coexpressing CD38/HLA-DR) was analyzed on blood
      specimens from 833 HIV-1-infected patients on ART for >=96 weeks with concurrent
      plasma HIV RNA (vRNA) <=200 copies per milliliter. Factors associated with CD8 T
      cell activation were assessed using generalized estimating equations to
      incorporate longitudinal measurements (median 4/participant). RESULTS:
      Participants were 84% men, 47% white, 28% black, and 22% Hispanic, with median
      pre-ART age 38 years and median ART exposure 144 weeks. CD8 T-cell activation was
      higher at timepoints when vRNA was 51-200 versus <=50 copies per milliliter [mean
      CD8 T-cell activation 23.4% vs. 19.7%; adjusted difference: 1.7% (95% confidence
      interval: 0.1 to 3.4), P = 0.042]. Restricting to vRNA <=50 copies per
      milliliter, multivariable models showed the following factors associated with
      higher CD8 T-cell activation: older age [>=45 vs. <=30 years: 3.6% (1.4 to 5.7),
      P = 0.004], hepatitis C virus antibody positivity [3.6% (0.9 to 6.2), P = 0.032],
      Hispanic vs. white [7.2% (5.3 to 9.0), P < 0.001], lower concurrent CD4 count
      [<=200 vs. >500 cells/mm: 2.2% (0.7 to 3.7), P < 0.001], lower concurrent CD4/CD8
      ratio [-2.6% (-3.7 to -1.5) per 0.5 unit increase, P < 0.001], and higher pre-ART
      CD8 T-cell activation [2.0% (1.6 to 2.5) per 10% higher, P < 0.001]. CONCLUSIONS:
      In participants included in our analysis, residual low-level viremia between 51
      and 200 copies per milliliter during ART was shown to be associated with greater
      CD8 T-cell activation than full suppression to <50 copies per milliliter. Older
      age, hepatitis C virus antibody positivity, race/ethnicity, higher pre-ART CD8 T
      cell activation, and lower concurrent CD4/CD8 ratio and CD4 T-cell count also
      contribute to greater CD8 T-cell activation during suppressive ART.

PMID- 25072611
TI  - The effect of tuberculosis treatment on virologic and immunologic response to
      combination antiretroviral therapy among South African children.
AB  - BACKGROUND: Many HIV-infected children are diagnosed with tuberculosis (TB), but
      the effect of TB treatment on virologic and immunologic response to combination
      antiretroviral therapy (cART) is not well documented. METHODS: Secondary analysis
      of a prospective cohort of cART-naive HIV-infected South African children aged 0
      8 years initiating cART to assess the effect of TB treatment at the time of cART
      initiation on virologic suppression (HIV RNA < 50 copies/mL), virologic rebound
      (HIV RNA > 1000 copies/mL after suppression), and CD4 cell percent (CD4%)
      increase during the first 24 months of cART. RESULTS: Of 199 children (median age
      2.1 years), 92 (46%) were receiving TB treatment at cART initiation. Children
      receiving and not receiving TB treatment at cART initiation had similar median
      baseline HIV RNA (5.4 vs. 5.6 copies/mL), median time to virologic suppression
      (6.2 months in each group, adjusted hazard ratio, 1.36, 95% confidence interval:
      0.94 to 1.96), and rates of virologic rebound by 24 months (23% vs. 24%, adjusted
      hazard ratio 1.53, 95% confidence interval: 0.71 to 3.30). Children on TB
      treatment had significantly lower median CD4% at baseline (15.3% vs. 18.8%, P <
      0.01) and during the first 12 months of cART but experienced similar median
      increases in CD4% at 6 months (9.9% vs. 9.6%), 12 months (14.2% vs. 11.9%), and
      24 months of cART (14.5% vs. 14.2%). Exploratory analyses suggest that children
      receiving lopinavir/ritonavir-based cART and TB treatment may have inferior
      virologic and immunologic response compared with children receiving efavirenz
      based cART. CONCLUSIONS: Receiving TB treatment at the time of cART initiation
      did not substantially affect virologic or immunologic response to cART in young
      children.

PMID- 25072612
TI  - PPARgamma2 Pro12Ala polymorphism is associated with sustained virological
      response in HIV/HCV-coinfected patients under HCV therapy.
AB  - OBJECTIVES: To analyze whether peroxisome proliferator-activated receptor gamma
      (PPARgamma2) rs1801282 (Pro12Ala) polymorphism is associated with the response to
      pegylated-interferon-alpha plus ribavirin treatment in HIV/hepatitis C virus
      (HCV)-coinfected patients, and whether it is able to predict the outcome of HCV
      treatment. DESIGN: Retrospective follow-up study. METHODS: Two hundred eighty
      five naive patients, who started HCV-treatment, were genotyped for PPARgamma2 and
      interleukin 28B polymorphisms. Genetic data were analyzed under dominant
      inheritance model. Sustained virological response (SVR) was defined as
      undetectable HCV viremia through 24 weeks after the end of HCV treatment.
      RESULTS: The variables significantly associated with SVR in a multivariate
      analysis were HCV-genotype (GT) 3 {adjusted odds ratio [aOR] = 7.66 [95% of
      confidence interval (95% CI): 3.96 to 14.81] P < 0.001}, HCV-viremia <500,000
      IU/mL [aOR = 2.20 (95% CI: 1.16 to 4.15] P = 0.015), no/mild liver fibrosis (F <
      2) [aOR = 1.92 (95% CI: 1.08 to 3.42) P = 0.026], IL28B rs12980275 AA genotype
      [aOR = 2.70 (95% CI: 1.54 to 4.71) P < 0.001], and PPARgamma2 rs1801282 CG/GG
      genotype [aOR = 2.93 (95% CI: 1.27 to 6.72) P = 0.011]. When PPARgamma2 rs1801282
      genotype was included in a decision tree analysis, HCV-GT3 patients with CG/GG
      genotype had increased SVR from 80.3% to 100%. In GT1/4 patients, rs12980275 AA
      carriers had increased SVR from 58.7% to 78.6%, and rs12980275 AG/GG carriers had
      increased SVR from 28.7% to 35.7%. The overall percentage of patients correctly
      classified was 71.6% and the area under the receiver operating characteristic
      curves was 0.766 +/- 0.028. CONCLUSIONS: The presence of PPARgamma2 rs1801282 G
      allele (Ala variant) was associated with increased odds for achieving SVR in
      HIV/HCV-coinfected patients on HCV treatment.

PMID- 25072613
TI  - Race and other risk factors for incident proteinuria in a national cohort of HIV
      infected veterans.
AB  - BACKGROUND: Proteinuria in human immunodeficiency virus (HIV)-infected
      individuals has been associated with poorer outcomes. We examined risk factors
      associated with the development of proteinuria in a national registry of HIV
      infected veterans. METHODS: A total of 21,129 HIV-infected veterans of black and
      white race without preexisting kidney disease were receiving health care in the
      Veterans' Health Administration (VHA) medical system between 1997 and 2011. Using
      the VHA electronic record system, we identified kidney-related risk factors
      (hypertension, diabetes, and cardiovascular disease) and HIV-related risk factors
      (CD4 lymphocyte count, HIV RNA level, hepatitis C virus, and hepatitis B virus)
      for developing proteinuria. Proteinuria was defined by 2 consecutive dipstick
      measures of 1 or higher. The Fine-Gray competing risk model was used to estimate
      association between clinical variables and incident proteinuria, while accounting
      for intervening mortality events. RESULTS: During follow-up (median = 5.3 years),
      7031 patients developed proteinuria. Overall, black race compared with white race
      was associated with a higher risk of proteinuria {hazard ratio [95% confidence
      interval (CI)] = 1.51 [1.43 to 1.59]}, but the association was stronger at
      younger ages (P interaction <0.001). Age-stratified risk of proteinuria for
      blacks relative to whites was greatest among veterans <30 years [2.19 (1.66 to
      2.89)] and the risk diminished with increasing age [1.14 (0.97 to 1.34) for >60
      years]. We found the race difference to be stronger for the outcome of 2 or
      higher proteinuria [2.13 (1.89 to 2.39)]. Both HIV-related and traditional risk
      factors were also associated with incident proteinuria (P < 0.05). CONCLUSIONS:
      Compared with whites, risk of proteinuria was higher in black veterans with HIV
      infection, particularly at younger ages. In both races, HIV- and kidney-related
      risk factors were associated with higher proteinuria risk.

PMID- 25072614
TI  - Needle autopsy to establish the cause of death in HIV-infected hospitalized
      adults in Uganda: a comparison to complete autopsy.
AB  - INTRODUCTION: Minimal invasive but accurate methods to establish the cause of
      death in HIV-infected patients are needed. We studied the agreement in cause of
      death between blind and ultrasound-guided needle autopsy and complete autopsy in
      HIV-infected patients in Uganda. METHODS: We subsequently performed a blind and
      ultrasound-guided needle autopsy followed by a complete autopsy in HIV-infected
      adults who died during hospitalization. Two teams of pathologists reviewed the
      tissue from either the needle autopsies or the complete autopsy and formulated
      the major diagnoses, that is, diseases directly contributing to death. The
      primary outcome was concordance in major diagnosis between needle and complete
      autopsies. RESULTS: We performed 96 blind needle and complete autopsies and 95
      ultrasound-guided needle autopsies. Concordance in major diagnosis between blind
      needle and complete autopsy was 50%. For the main major diagnosis, tuberculosis
      (TB) concordance was higher (71%; P < 0.01). Blind needle autopsy identified at
      least 1 major diagnosis in 60% of patients; and in 46%, there was complete
      concordance for all major diagnoses. The main reason for discordance was sampling
      error of the lesion. Concordance with the addition of ultrasound guidance was 52%
      for all major diagnoses and 79% for TB. Major diagnoses were mainly identified in
      tissue cores from the liver (76%) and the spleen (82%). DISCUSSION: Blind needle
      autopsy identified half of the major diagnosis. The addition of ultrasound
      guidance did not significantly improve the performance of needle autopsy. Needle
      autopsy is a valuable method to confirm causes of death in HIV-infected patients,
      especially for highly prevalent diseases like TB.

PMID- 25072615
TI  - Association between HIV-1 coreceptor usage and resistance to broadly neutralizing
      antibodies.
AB  - BACKGROUND: Recently discovered broadly neutralizing antibodies have revitalized
      hopes of developing a universal vaccine against HIV-1. Mainly responsible for new
      infections are variants only using CCR5 for cell entry, whereas CXCR4-using
      variants can become dominant in later infection stages. METHODS: We performed a
      statistical analysis on two different previously published data sets. The first
      data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization
      titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04,
      PG9, and PG16. The second data set contained env sequences of viral variants
      extracted from HIV-1-infected humanized mice treated with the antibody PGT128 and
      from untreated control mice. RESULTS: For the panel of 199 diverse HIV-1
      isolates, we found a statistically significant association between viral
      resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010,
      respectively). Our analysis of viral variants from HIV-1-infected humanized mice
      under treatment with the broadly neutralizing antibody PGT128 indicated that
      certain antibodies might drive a viral population toward developing CXCR4
      coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and
      control measurement). CONCLUSIONS: These analyses highlight the importance of
      accounting for a possible coreceptor usage bias pertaining to the effectiveness
      of an HIV vaccine and to passive antibody transfer as therapeutic approach.

PMID- 25072617
TI  - Bone mineral density over 96 weeks in adults failing first-line therapy
      randomized to raltegravir/lopinavir/ritonavir compared with standard second-line
      therapy.
AB  - OBJECTIVE: To compare bone mineral density (BMD) changes over 96 weeks in adults
      virologically failing standard first-line therapy, randomized to raltegravir plus
      lopinavir/ritonavir (RAL + LPV/r) or conventional 2-3 nucleoside/nucleotide
      reverse transcriptase inhibitors [N(t)RTIs] + LPV/r second-line therapy. METHODS:
      Participants underwent dual-energy x-ray absorptiometry at baseline and weeks 48
      and 96 to measure total hip and lumbar spine BMD. Analyses were adjusted for
      gender, body mass index, and smoking. Linear regression was used to compare
      between-group differences, logistic regression for low BMD (hip or spine Z-score
      <= -2) incidence, and multivariate linear regression to determine predictors of
      BMD change. This work represents the extension and final results of the
      previously published initial 48 weeks of the study. RESULTS: The population
      included 210 adults from 5 middle-income countries: 52% females, 52% Asians, 43%
      Africans, mean age, 39 years (SD, 8 years). In the 2-3 N(t)RTI group (vs. RAL),
      BMD reduction was greater at the spine (mean change, -4.9% vs. -3.5%; adjusted
      difference, -1.9%; 95% confidence interval: -3.3 to -0.5%, P = 0.009) and hip (
      4.1% vs. -2.2%; -1.9%; -3.4 to -0.4; P = 0.012). BMD decrease was greatest at 48
      weeks with stabilization to week 96. Overall, low BMD occurred in 15 participants
      (7.9%), with no between-group differences. Independent predictors for bone loss
      included lower body mass index (regression coefficient: hip, -0.18% and spine, 
      0.26% per 1 kg/m), longer tenofovir exposure (hip, -0.74% and spine, -1.0% per
      year), greater change in CD4 to week 12 (hip, -5.11% per 10-fold higher), and
      higher baseline HIV-RNA (spine, -0.7% per 10-fold higher). CONCLUSIONS: Over 96
      weeks, there was greater BMD decrease with 2-3 N(t)RTI + LPV/r compared with RAL
      + LPV/r; the relative decrease at the spine was greater than the hip. BMD
      decreases with second-line antiretroviral therapy largely occurred in the first
      48 weeks with stabilization, but no recovery thereafter.

PMID- 25072616
TI  - Risk factors for preterm birth among HIV-infected pregnant Ugandan women
      randomized to lopinavir/ritonavir- or efavirenz-based antiretroviral therapy.
AB  - BACKGROUND: Protease inhibitor-based antiretroviral therapy (ART) has been
      associated with preterm birth in some studies. We examined risk factors for
      preterm birth among women randomized to lopinavir/ritonavir (LPV/r)- or efavirenz
      (EFV)-based ART. METHODS: This was a planned secondary analysis of the PROMOTE
      Pregnant Women and Infants Study, an open-label, randomized controlled trial
      comparing the risk of placental malaria among HIV-infected, ART-naive pregnant
      Ugandan women assigned to initiate LPV/r- or EFV-based ART at 12-28 weeks
      gestation. Gestational age was determined based on last menstrual period and
      ultrasound biometry. All women received bednets and trimethoprim
      sulfamethoxazole. Stillbirths, spontaneous abortions, and multiple gestations
      were excluded from the primary analysis. Potential risk factors for preterm birth
      (<37 weeks gestation) were evaluated by univariate and multivariate logistic
      regression. RESULTS: Three hundred fifty-six women were included in this
      analysis. At enrollment, median gestational age was 21 weeks and median CD4 cell
      count was 368 cells per cubic millimeter. 14.7% of deliveries in the EFV arm and
      16.2% in the LPV/r arm were preterm. Preterm birth was associated with
      gestational weight gain below 0.1 kg/week versus 0.1 kg/week or more [odds ratio
      (OR) = 2.49; 95% confidence interval (CI): 1.38 to 4.47; P = 0.003]. Neither ART
      regimen of LPV/r versus EFV (OR = 1.12; 95% CI: 0.63 to 2.00; P = 0.69) nor
      placental malaria (OR = 0.74; 95% CI: 0.38 to 1.44; P = 0.37) was associated with
      preterm birth. CONCLUSIONS: LPV/r was not associated with an increased risk of
      preterm birth compared with EFV. However, interventions are needed to address
      modifiable risk factors for preterm birth, such as nutritional status
      (ClinicalTrials.gov, NCT00993031).

PMID- 25072618
TI  - Endothelial vacuolization induced by highly permeable silicon membranes.
AB  - Assays for initiating, controlling and studying endothelial cell behavior and
      blood vessel formation have applications in developmental biology, cancer and
      tissue engineering. In vitro vasculogenesis models typically combine complex
      three-dimensional gels of extracellular matrix proteins with other stimuli like
      growth factor supplements. Biomaterials with unique micro- and nanoscale features
      may provide simpler substrates to study endothelial cell morphogenesis. In this
      work, patterns of nanoporous, nanothin silicon membranes (porous nanocrystalline
      silicon, or pnc-Si) are fabricated to control the permeability of an endothelial
      cell culture substrate. Permeability on the basal surface of primary and
      immortalized endothelial cells causes vacuole formation and endothelial
      organization into capillary-like structures. This phenomenon is repeatable,
      robust and controlled entirely by patterns of free-standing, highly permeable pnc
      Si membranes. Pnc-Si is a new biomaterial with precisely defined micro- and
      nanoscale features that can be used as a unique in vitro platform to study
      endothelial cell behavior and vasculogenesis. 

PMID- 25072619
TI  - Influence of phase separation on the devitrification of 45S5 bioglass.
AB  - The devitrification of the 45S5 variety of bioactive glasses (BGs) in relation to
      phase separation is studied with scanning electron microscopy, X-ray powder
      diffraction, Fourier transform infrared spectroscopy, differential scanning
      calorimetry and positron annihilation lifetime spectroscopy techniques. It is
      shown that the type of phase separation (such as spinodal vs. droplet-like) has a
      pronounced effect on the activation energy of viscous flow and crystallization,
      the onset temperature of crystallization and the void size distribution at the
      nanoscale. Generally, the Johnson-Mehl-Avrami (JMA) relation does not describe
      crystallization kinetics in bulk 45S5 BG. However, for powder samples (<300 MUm)
      the difference in crystallization kinetics, which is surface-driven for the two
      kinds of glasses, becomes much smaller, and can be described with the JMA
      relation under some circumstances.

PMID- 25072620
TI  - Human herpesvirus 6 reactivation before engraftment is strongly predictive of
      graft failure after double umbilical cord blood allogeneic stem cell
      transplantation in adults.
AB  - Our main objective was to determine new factors associated with engraftment and
      single-unit predominance after double umbilical cord blood (UCB) allogeneic stem
      cell transplantation. Engraftment occurred in 78% of cases in this retrospective
      study including 77 adult patients. Three-year overall survival, disease-free
      survival, relapse incidence, and nonrelapse mortality were 55 +/- 6%, 44 +/- 6%,
      33 +/- 5%, and 23 +/- 4%, respectively. In multivariate analysis, Human
      herpesvirus 6 reactivation during aplasia (hazard ratio [HR] = 2.63; 95%
      confidence interval [CI]: 1.64-4.17; p < 0.001), younger recipient age (<53
      years) (HR = 1.97; 95% CI: 1.16-3.35; p = 0.012), and lower human leukocyte
      antigen matching between the two units (3 of 6 or 4 of 6) (HR = 2.09; 95%
      confidence interval: 1.22-3.59; p = 0.013) were the three factors independently
      associated with graft failure. Also, factors independently predicting the losing
      UCB unit were younger age of the UCB unit (odds ratio [OR] = 1.01; 95% CI: 1
      1.02; p = 0.035), lower CD34(+) cell dose contained in the UCB unit (<= 0.8 *
      10(5)/kg) (OR = 2.55; 95% CI: 1.05-6.16; p = 0.04), and presence of an ABO
      incompatibility between the UCB unit and the recipient (OR = 2.53; 95% CI: 1.15
      5.53; p = 0.02). Thus, Human herpesvirus 6 reactivation during aplasia, lower
      unit-unit human leukocyte antigen matching, and younger UCB unit age, as new
      unfavorable predictive factors, may represent new parameters to take into account
      after double UCB allogeneic stem-cell transplantation in adults. These results
      need to be confirmed prospectively, as they may influence unit selections and
      patient outcomes.

PMID- 25072622
TI  - Microbial biosynthesis of medicinally important plant secondary metabolites.
AB  - Secondary metabolites derived from plants are a valuable source of
      pharmaceuticals, nutraceuticals, and cosmetics. To harness the potential of these
      natural products, reliable methods must be developed for their rapid and
      sustainable resupply. Microbial production of plant secondary metabolites through
      the heterologous expression of plant biosynthetic genes represents one such
      solution. This highlight focuses on recent advances in the microbial biosynthesis
      of plant secondary metabolites including terpenoids, flavonoids, and alkaloids as
      well as providing a brief insight into the current limitations and future
      prospects.

PMID- 25072621
TI  - Human B-cell cancer cell lines as a preclinical model for studies of drug effect
      in diffuse large B-cell lymphoma and multiple myeloma.
AB  - Drug resistance in cancer refers to recurrent or primary refractory disease
      following drug therapy. At the cellular level, it is a consequence of molecular
      functions that ultimately enable the cell to resist cell death-one of the
      classical hallmarks of cancer. Thus, drug resistance is a fundamental aspect of
      the cancer cell phenotype, in parallel with sustained proliferation, immortality,
      angiogenesis, invasion, and metastasis. Here we present a preclinical model of
      human B-cell cancer cell lines used to identify genes involved in specific drug
      resistance. This process includes a standardized technical setup for specific
      drug screening, analysis of global gene expression, and the statistical
      considerations required to develop resistance gene signatures. The state of the
      art is illustrated by the first-step classical drug screen (including the CD20
      antibody rituximab, the DNA intercalating topoisomerase II inhibitor doxorubicin,
      the mitotic inhibitor vincristine, and the alkylating agents cyclophosphamide and
      melphalan) along with the generation of gene lists predicting the
      chemotherapeutic outcome as validated retrospectively in clinical trial datasets.
      This B-cell lineage-specific preclinical model will allow us to initiate a range
      of laboratory studies, with focus on specific gene functions involved in
      molecular resistance mechanisms. 

PMID- 25072623
TI  - Health literacy and heart failure management in patient-caregiver dyads.
AB  - BACKGROUND: Older adults with heart failure (HF) often need caregivers to assist
      with care, yet little is known about the health literacy of both patients and
      their caregivers. The objective of this study was to assess health literacy and
      the relationship between health literacy and HF self-care in HF patient-caregiver
      dyads. METHODS AND RESULTS: Seventeen patient-caregiver dyads were recruited.
      Dyads completed a measure of HF self-care and 2 measures of health literacy: 3
      validated questions and a nutrition label reading task. Patients were older than
      caregivers and the majority of both patients and caregivers were female.
      Caregivers had higher health literacy by both the health literacy questions (P =
      .001) and label-reading measure (P = .001). All caregivers had adequate health
      literacy as assessed by the 3 questions, but 29% had inadequate health literacy
      according to the label-reading task. Caregivers and patients scored adequately in
      HF maintenance but inadequately in management and confidence domains.
      CONCLUSIONS: Caregivers had better health literacy than patients; however, the
      task-oriented label-reading measure revealed poorer health literacy than the self
      report measure. Measures of health literacy that reflect day to day tasks may be
      more illuminating than the 3 questions.

PMID- 25072624
TI  - General synthetic approach to heterostructured nanocrystals based on noble metals
      and I-VI, II-VI, and I-III-VI metal chalcogenides.
AB  - Solid metal precursors (alloys or monometals) can serve both as a starting
      template and as a source material for chemical transformation to metal
      chalcogenides. Herein, we develop a simple solution-based strategy to obtain
      highly monodisperse noble-metal-based heterostructured nanocrystals from such
      precursor seeds. By utilizing chemical and structural inhomogeneity of these
      metal seeds, in this work, we have synthesized a total of five I-VI (Ag2S, Ag2Se,
      Ag3AuS2, Ag3AuSe2, and Cu9S5), three II-VI (CdS, CdSe, and CuSe), and four I-III
      VI (AgInS2, AgInSe2, CuInS2, and CuInSe2) chalcogenides, together with their
      fifteen associated heterodimers (Au-Ag2S, Au-Ag2Se, Au-Ag3AuS2, Au-Ag3AuSe2, Au
      AgInS2, Au-AgInSe2, Au-CdS, Au-CdSe, Ag-Ag2S, Ag-AgInS2, Au-Cu9S5, Au-CuInS2, Au
      CuSe, Au-CuInSe2, and Pt-AgInS2) to affirm the process generality. Briefly, by
      adding elemental sulfur or selenium to AuAg alloy seeds and tuning the reaction
      conditions, we can readily obtain phase-pure Au-Ag2S, Au-Ag2Se, Au-Ag3AuS2, and
      Au-Ag3AuSe2 heterostructures. Similarly, we can also fabricate Au-AgInS2 and Au
      AgInSe2 heterostructures from the AuAg seeds by adding sulfur/selenium and indium
      precursors. Furthermore, by partial or full conversion of Ag seeds, we can
      prepare both single-phase Ag chalcogenide nanocrystals and Ag-based
      heterostructures. To demonstrate wide applicability of this strategy, we have
      also synthesized Au-based binary and ternary Cu chalcogenide (Au-Cu9S5, Au-CuSe,
      Au-CuInS2, and Au-CuInSe2) heterostructures from alloy seeds of AuCu and Pt
      chalcogenides (e.g., Pt-AgInS2) from alloy seeds of PtAg. The structure and
      composition of the above products have been confirmed with X-ray diffraction,
      high-resolution transmission electron microscopy, X-ray photoelectron
      spectroscopy, and energy-dispersive X-ray spectroscopy methods. A kinetic
      investigation of the formation mechanism of these heterostructures is brought
      forward using Au-AgInS2 and Ag-CuInS2 as model examples. 

PMID- 25072626
TI  - Short neuropeptide F (sNPF) is a stage-specific suppressor for juvenile hormone
      biosynthesis by corpora allata, and a critical factor for the initiation of
      insect metamorphosis.
AB  - Molting and metamorphosis are essential events for arthropod development, and
      juvenile hormone (JH) and its precursors play critical roles for these events. We
      examined the regulation of JH biosynthesis by the corpora allata (CA) in Bombyx
      mori, and found that intact brain-corpora cardiaca (CC)-CA complexes produced a
      smaller amount of JH than that in CC-CA complexes and CA alone throughout the 4th
      and 5th (last) instar stadium. The smaller amount of synthesis was due to
      allatostatin-C (AST-C) produced by the brain. The CC synthesized short
      neuropeptide F (sNPF) that also suppressed the JH synthesis, but only in day 3
      4th stadium and after the last larval ecdysis. For the suppression, both peptides
      prevented the expression of some of the distinct JH biosynthetic enzymes in the
      mevalonate pathway. Allatotropin (AT) stimulated sNPF expression in the CC of day
      1 5th instar stadium, not of day 3 4th; therefore the stage-specific inhibition
      of JH synthesis by sNPF was partly due to the stimulative action of AT on the
      sNPF expression besides the stage-specific expression of the sNPF receptors in
      the CA, the level of which was high in day 2 4th and day 0 5th instar larvae. The
      cessation of JH biosynthesis in the last instar larvae is a key event to initiate
      pupal metamorphosis, and both sNPF and AST-C are key factors in shutting down JH
      synthesis, along with the decline of ecdysone titer and dopamine. 

PMID- 25072625
TI  - The proteins encoded by the Drosophila Planar Polarity Effector genes inturned,
      fuzzy and fritz interact physically and can re-pattern the accumulation of
      "upstream" Planar Cell Polarity proteins.
AB  - The frizzled/starry night pathway regulates planar cell polarity in a wide
      variety of tissues in many types of animals. It was discovered and has been most
      intensively studied in the Drosophila wing where it controls the formation of the
      array of distally pointing hairs that cover the wing. The pathway does this by
      restricting the activation of the cytoskeleton to the distal edge of wing cells.
      This results in hairs initiating at the distal edge and growing in the distal
      direction. All of the proteins encoded by genes in the pathway accumulate
      asymmetrically in wing cells. The pathway is a hierarchy with the Planar Cell
      Polarity (PCP) genes (aka the core genes) functioning as a group upstream of the
      Planar Polarity Effector (PPE) genes which in turn function as a group upstream
      of multiple wing hairs. Upstream proteins, such as Frizzled accumulate on either
      the distal and/or proximal edges of wing cells. Downstream PPE proteins
      accumulate on the proximal edge under the instruction of the upstream proteins. A
      variety of types of data support this hierarchy, however, we have found that when
      over expressed the PPE proteins can alter both the subcellular location and level
      of accumulation of the upstream proteins. Thus, the epistatic relationship is
      context dependent. We further show that the PPE proteins interact physically and
      can modulate the accumulation of each other in wing cells. We also find that over
      expression of Frtz results in a marked delay in hair initiation suggesting that
      it has a separate role/activity in regulating the cytoskeleton that is not shared
      by other members of the group.

PMID- 25072627
TI  - The contrasting roles of primary cilia and cytonemes in Hh signaling.
AB  - Hedgehog (Hh) is a paracrine signaling protein with major roles in development
      and disease. In vertebrates and invertebrates, Hh signal transduction is carried
      out almost entirely by evolutionarily conserved components, and in both,
      intercellular movement of Hh is mediated by cytonemes - specialized filopodia
      that serve as bridges that bring distant cells into contact. A significant
      difference is the role of the primary cilium, a slender, tubulin-based
      protuberance of many vertebrate cells. Although the primary cilium is essential
      for Hh signaling in cells that have one, most Drosophila cells lack a primary
      cilium. This perspective addresses the roles of primary cilia and cytonemes, and
      proposes that for Hh signaling, the role of primary cilia is to provide a
      specialized hydrophobic environment that hosts lipid-modified Hh and other
      components of Hh signal transduction after Hh has traveled from elsewhere in the
      cell. Implicit in this model is the idea that initial binding and uptake of Hh is
      independent of and segregated from the processes of signal transduction and
      activation.

PMID- 25072629
TI  - Detecting and Characterizing Pleiotropy: New Methods for Uncovering the
      Connection Between the Complexity of Genomic Architecture and Multiple
      phenotypes.

PMID- 25072628
TI  - Alcohol misuse among university staff: a cross-sectional study.
AB  - OBJECTIVES: To examine the prevalence of hazardous drinking among staff in a UK
      university and its association with key socio-demographic features. DESIGN: A
      cross-sectional study. SETTING: A university in the UK. PARTICIPANTS: All
      employees on the university employee database were eligible to participate. Those
      who completed and returned the questionnaire were included in the sample.
      Respondents were 131 university employees. PRIMARY AND SECONDARY OUTCOME
      MEASURES: An AUDIT cut-off score of >=8 was used as a measure of hazardous
      drinking. AUDIT total score as well as a score of >=1 in each of the three
      conceptual domains of alcohol consumption (questions 1-3), dependence symptoms
      (questions 4-6) and alcohol-related problems (questions 7-10) were used as
      indicators of levels of drinking and alcohol-related consequences. Secondary
      outcomes were employees' demographics. RESULTS: Over one third (35%) of
      respondents were classified as hazardous drinkers. Twenty three per cent reported
      having blackouts after drinking and 14% had injuries or had injured someone. The
      odds of being a hazardous drinker for an employee in central departments (Human
      Resources, Registry etc) is only one third of that of an employee in science and
      health-related departments (OR = 0.35, 95% CI = 0.14 to 0.91). The proportion of
      hazardous drinkers was higher in males compared to females (43% and 30%
      respectively), part-time compared to full-time (46% and 34% respectively), and
      academic compared to non-academic employees (39% and 32% respectively), although
      these were not statistically significant (p>0.05). Furthermore, age, religion and
      ethnic origin were not found to be significantly associated with hazardous
      drinking, although total scores were significantly lower for ethnic minorities
      compared to white employees (p = 0.019). CONCLUSIONS: In this study, hazardous
      drinking was highly prevalent among university employees. However, overt
      recruiting of staff to address sensitive issues such as alcohol misuse is
      problematic.

PMID- 25072630
TI  - Effect of groundwater--lake interactions on arsenic enrichment in freshwater
      beach aquifers.
AB  - Field measurements combined with numerical simulations provide insight into the
      water exchange, groundwater flow, and geochemical processes controlling the
      mobility of arsenic (As) in freshwater beach aquifers. Elevated dissolved As (up
      to 56 MUg/L) was observed 1-2 m below the shoreline at two sandy beaches on Lake
      Erie, Ontario, Canada. Water and solid-phase analyses suggest that Fe
      (hydr)oxides present below the shoreline accumulate As, creating a risk of high
      As in the beach aquifer. Groundwater flow simulations combined with vertical
      hydraulic gradient measurements indicate that wave-induced flow recirculations
      across the groundwater-lake interface are significant. These recirculations,
      which vary with wave intensity and lake water level fluctuations, set up redox
      and pH gradients, where Fe precipitates and subsequently sequesters As. The
      elevated As concentrations observed at both beaches, combined with the
      distribution of other dissolved species, suggest that the As enrichment may be
      naturally occurring. Regardless of the As source, the interacting hydrologic and
      geochemical processes revealed may have important implications for the flux of As
      and also other oxyanions, such as phosphate, across the groundwater-lake
      interface in nearshore areas of the Great Lakes. 

PMID- 25072632
TI  - Choosing a proper exchange-correlation functional for the computational catalysis
      on surface.
AB  - To choose a proper functional among the diverse density functional approximations
      of the electronic exchange-correlation energy for a given system is the basis for
      obtaining accurate results of theoretical calculations. In this work, we first
      propose an approach by comparing the calculated DeltaE0 with the theoretical
      reference data based on the corresponding experimental results in a gas phase
      reaction. With DeltaE0 being a criterion, the three most typical and popular
      exchange-correlation functionals (PW91, PBE and RPBE) were systematically
      compared in terms of the typical Fischer-Tropsch synthesis reactions in the gas
      phase. In addition, verifications of the geometrical and electronic properties of
      modeling catalysts, as well as the adsorption behavior of a typical probe
      molecule on modeling catalysts are also suggested for further screening of proper
      functionals. After a systematic comparison of CO adsorption behavior on Co(0001)
      calculated by PW91, PBE, and RPBE, the RPBE functional was found to be better
      than the other two in view of FTS reactions in gas phase and CO adsorption
      behaviors on a cobalt surface. The present work shows the general implications
      for choosing a reliable exchange-correlation functional in the computational
      catalysis of a surface. 

PMID- 25072631
TI  - Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide
      containing nanoliposome in a glioma model.
AB  - As a glycosphingolipid that can bind to several extracellular matrix proteins,
      sulfatide has the potential to become an effective targeting agent for tumors
      overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting
      toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN)
      encapsulation approach was employed to improve treatment efficacy and reduce side
      effects of free DOX. This study analysed in vitro characteristics of sulfatide
      containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as
      well as biodistribution, therapeutic efficacy, and systemic toxicity in a human
      glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug
      to lipid ratio (0.5?1) and a remarkable in vitro stability. Moreover, DOX
      encapsulated in SCN was shown to be delivered into the nuclei and displayed
      prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX
      nanodrug has favourable pharmacokinetic attributes in terms of prolonged
      circulation time, reduced volume of distribution and enhanced bioavailability in
      healthy rats. As a result of the improved biodistribution, an enhanced treatment
      efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug.
      Finally, a reduction in the accumulation of DOX in the drug's principal toxicity
      organs achieved by SCN-DOX led to the diminished systemic toxicity as evident
      from the plasma biochemical analyses. Thus, SCN has the potential to be an
      effective and safer nano-carrier for targeted delivery of therapeutic agents to
      tumors with elevated expression of tenascin-C in their microenvironment. 

PMID- 25072633
TI  - Modulation of proopiomelanocortin gene expression by ethanol in mouse anterior
      pituitary corticotrope tumor cell AtT20.
AB  - In humans, alcoholism is associated with a decrease in basal ACTH and cortisol
      levels, and blunted pituitary ACTH responses to administered corticotropin
      releasing hormone (CRH) during active drinking and after long-term abstinence.
      Preclinical studies indicate that a persistent decrease in pituitary activation
      after chronic exposure to ethanol is due to a direct effect of ethanol on the
      corticotrope of the anterior pituitary. The present studies were undertaken to
      determine if ethanol has effects on proopiomelanocortin (POMC) gene transcription
      activity in mouse anterior pituitary corticotrope tumor cell AtT20. We measured
      the levels of the POMC primary nuclear RNA transcript (PT), processing
      intermediate, and mature mRNA in the nucleus and the levels of the POMC mRNA in
      the cytoplasm after treatment of AtT20 cells with 5-15 mM concentrations of
      ethanol. After 15 mM ethanol for 60 to 120 min, the POMC PT levels were
      significantly decreased. This decreased POMC gene transcription activity was
      coupled with a significant reduction of the POMC cytoplasmic mRNA levels. After
      ethanol for 4h, however, both the decreases were no longer observed. After 8h, a
      decrease in the ACTH secretion in the medium was found. We further investigated
      if CRH or glutamate modulates the effects of ethanol on the POMC gene
      transcription activity. CRH at 10nM after 60 min increased the POMC PT levels,
      and 15mM ethanol attenuated the effect of CRH on the nuclear transcription
      activity. Glutamate receptor proteins, including NMDA receptor subtype NR1 (but
      not NR2A or NR2B) and GluR2, were identified by Western immunoblot analysis in
      AtT20 cells, with similar sizes to those in mouse hypothalamus. The inhibitory
      effect of 60 min ethanol at 5 to 15 mM on the POMC PT levels was attenuated by 50
      MUM L-glutamate. Together, our data showed that: (1) ethanol treatment in
      intoxicate doses significantly inhibited POMC gene transcription activity in a
      dose- and time-dependent manner in AtT20 cells, and (2) the POMC gene
      transcription activity in response to CRH or glutamate was altered by ethanol.
      Our results suggest that ethanol has an inhibitory effect on the POMC gene
      transcription activity in the anterior pituitary corticotrope, which may
      contribute to the persistent decrease in pituitary activation after chronic
      ethanol exposure.

PMID- 25072634
TI  - Hydrogel thin film with swelling-induced wrinkling patterns for high-throughput
      generation of multicellular spheroids.
AB  - Three-dimensional (3D) multicellular spheroids (MCSs) mimic the structure and
      function of real tissue much better than the conventional 2D cell monolayers,
      however, their application was severely hindered by difficulties in their
      generation. An ideal method for MCS fabrication should produce spheroids with
      narrow size distribution and allow for control over their size. The method should
      also be simple, cheap, and scalable. Here, we use patterned nonadhesive poly(2
      hydroxyethyl methacrylate) hydrogel films to guide the self-assembly of cells.
      The films were fabricated directly in the wells of cell culture plates. They were
      patterned spontaneously by swelling in water, without the use of any template or
      specialized facilities. When cell suspension is added, the cells settle down by
      gravity to the bottom. Because of the presence of the wrinkling pattern composed
      of uniformed microcaves, the cells accumulate to the center of the microcaves and
      gradually self-assemble into MCSs. Using this method, monodisperse MCSs were
      generated. The size of the spheroids can be facilely controlled by the number of
      cells seeded. The method is compatible with the conventional monolayer cell
      culture method. Thousands of spheroids can be generated in a single well. We
      expect this method will pave the way for the application of MCSs in various
      biomedical areas. 

PMID- 25072635
TI  - Flowering responses to seasonal cues: what's new?
AB  - Seasonal cues of day length or winter cold trigger flowering of many species.
      Forward and reverse genetic approaches are revealing the mechanisms by which
      these responses are conferred. Homologues of the Arabidopsis thaliana protein
      FLOWERING LOCUS T (FT) are widely used to mediate seasonal responses to day
      length and act as graft-transmissible promoters or repressors of flowering.
      Winter cold in A. thaliana promotes flowering by repressing transcription of the
      MADS box gene FLOWERING LOCUS C (FLC). The mechanism by which this occurs
      involves a complex interplay of different forms of long noncoding RNAs induced at
      the FLC locus during cold and changes in the chromatin of FLC. In perennial
      relatives of A. thaliana, flowering also requires the age-dependent
      downregulation of miRNA156 before winter. 

PMID- 25072636
TI  - Investigation of nonfouling polypeptides of poly(glutamic acid) with lysine side
      chains synthesized by EDC.HCl/HOBt chemistry.
AB  - Nonfouling polypeptides with homogenous alternating charges draw peoples'
      attentions for their potential capability in biodegradation. Homogenous glutamic
      acid (E) and lysine (K) polypeptides were proposed and synthesized before. In
      this work, a new polypeptide formed by poly(glutamic acid) with lysine side
      chains (poly(E)-K) was synthesized by facile EDC.HCl/HOBt chemistry and
      investigated. Results show that these polypeptides also have good nonspecific
      protein resistance determined by enzyme-linked immunosorbent assay. The lowest
      nonspecific adsorption of the model proteins, anti-IgG and fibrinogen (Fg), on
      the self-assembling monolayers (SAMs) surface of poly(E)-K was only 3.3 +/- 1.8
      and 4.4 +/- 1.6%, respectively, when protein adsorption on tissue culture
      polystyrene surface was set as 100%. And, the relative nonspecific protein
      adsorption increases when the polypeptide molecular weight increases due to the
      repression of low density polymer brushes. Moreover, almost no obvious
      cytotoxicity and hemolytic activity in vitro were detected. This work suggests
      that polypeptides with various formats of homogenous balanced charges could
      achieve excellent nonspecific protein resistance, which might be the intrinsic
      reason for the coexistence of high concentration serum proteins in blood. 

PMID- 25072637
TI  - Occupational stress and subclinical atherosclerosis: a systematic review.
AB  - BACKGROUND: Stress is a common hazard in the work environment and is associated
      with multiple adverse health effects. The association between work-related stress
      (WRS) and cardiovascular disease has been established in a number of
      epidemiological studies. METHODS: A systematic review was conducted according to
      the PRISMA statement of the English literature involving WRS and carotid artery
      intima media thickness (CIMT). RESULTS: Four cohorts and six cross-sectional
      studies of occupational stress and CIMT were identified. All cohorts and five of
      the cross-sectional studies reported a significant positive association, while
      one reported an inverse association of WRS and CIMT. DISCUSSION: The weight of
      the evidence that we were able to identify suggests that occupational stress
      results in an increased risk of atherosclerosis, assessed via CIMT. Studies that
      include longitudinal measures of stress and intermediate cardiac endpoints, with
      adequate accounting for confounders, are needed. Interventional studies should
      also be conducted to determine whether CIMT progression can be prevented with
      workplace stress reduction.

PMID- 25072638
TI  - Pigment dispersing factor regulates ecdysone biosynthesis via bombyx neuropeptide
      G protein coupled receptor-B2 in the prothoracic glands of Bombyx mori.
AB  - Ecdysone is the key hormone regulating insect growth and development. Ecdysone
      synthesis occurs in the prothoracic glands (PGs) and is regulated by several
      neuropeptides. Four prothoracicotropic and three prothoracicostatic factors have
      been identified to date, suggesting that ecdysone biosynthesis is intricately
      regulated. Here, we demonstrate that the neuropeptide pigment dispersing factor
      (PDF) stimulates ecdysone biosynthesis and that this novel signaling pathway
      partially overlaps with the prothoracicotropic hormone (PTTH) signaling pathway.
      We performed transcriptome analysis and focused on receptors predominantly
      expressed in the PGs. From this screen, we identified a candidate orphan G
      protein coupled receptor (GPCR), Bombyx neuropeptide GPCR-B2 (BNGR-B2). BNGR-B2
      was predominantly expressed in ecdysteroidogenic tissues, and the expression
      pattern in the PGs corresponded to the ecdysteroid titer in the hemolymph.
      Furthermore, we identified PDF as a ligand for BNGR-B2. PDF stimulated ecdysone
      biosynthesis in the PGs, but the stimulation was only observed in the PGs during
      a specific larval stage. PDF did not affect the transcript level of known
      ecdysone biosynthetic enzymes, and inhibiting transcription did not suppress
      ecdysone biosynthesis, suggesting that the effects of PDF might be mediated by
      translational regulation and/or post-translational modification. In addition, the
      participation of protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K),
      target of rapamycin (TOR) and eukaryotic translation initiation factor 4E (eIF4E)
      binding protein (4E-BP) in the PDF signaling pathway was discovered. 

PMID- 25072639
TI  - Inter-individual variability of stone marten behavioral responses to a highway.
AB  - Efforts to reduce the negative impacts of roads on wildlife may be hindered if
      individuals within the population vary widely in their responses to roads and
      mitigation strategies ignore this variability. This knowledge is particularly
      important for medium-sized carnivores as they are vulnerable to road mortality,
      while also known to use available road passages (e.g., drainage culverts) for
      safely crossing highways. Our goal in this study was to assess whether this
      apparently contradictory pattern of high road-kill numbers associated with a
      regular use of road passages is attributable to the variation in behavioral
      responses toward the highway between individuals. We investigated the responses
      of seven radio-tracked stone martens (Martes foina) to a highway by measuring
      their utilization distribution, response turning angles and highway crossing
      patterns. We compared the observed responses to simulated movement parameterized
      by the observed space use and movement characteristics of each individual, but
      naive to the presence of the highway. Our results suggested that martens
      demonstrate a diversity of responses to the highway, including attraction,
      indifference, or avoidance. Martens also varied in their highway crossing
      patterns, with some crossing repeatedly at the same location (often coincident
      with highway passages). We suspect that the response variability derives from the
      individual's familiarity of the landscape, including their awareness of highway
      passage locations. Because of these variable yet potentially attributable
      responses, we support the use of exclusionary fencing to guide transient (e.g.,
      dispersers) individuals to existing passages to reduce the road-kill risk. 

PMID- 25072640
TI  - Frequency estimator for assessing of follow-on biologics.
AB  - For approval of generic drugs, the U.S. Food and Drug Administration (FDA)
      requires the evidence of bioequivalence in average bioavailability be provided.
      This is based on the Fundmental Bioequivalence Assumption from FDA that if two
      drug products are shown to be bioequivalent, it is assumed that they are
      therapeutically equivalent and can be used interchangeably. Recently, there are a
      few statistical considerations for assessing biosimilarity. In this article, we
      propose a new method based on a frequency estimator to evaluate biosimilarity;
      the large sample properties of the estimator, the power analysis, and calculation
      of the sample size are considered. Under a three-arm parallel design, the power
      comparison between the frequency estimator method and the other existing methods
      is studied through simulation, and the statistical test based on the proposed
      method is more powerful than for the other two methods. Simultaneously, we
      compared the relative performance of the three methods, and the empirical
      consistency and inconsistency probability are obtained in evaluating the
      biosimilarity. 

PMID- 25072642
TI  - Bring your own device into problem based learning tutorials.

PMID- 25072641
TI  - Gene expression analysis suggests bone development-related genes GDF5 and DIO2
      are involved in the development of Kashin-Beck disease in children rather than
      adults.
AB  - OBJECTIVE: To investigate the differences in gene expression between children and
      adults with Kashin-Beck disease (KBD). METHODS: 12 children with KBD and 12
      healthy children were selected and divided into 4 KBD vs. control pairs matched
      according to age and gender, with each pair having 3 KBD children and 3 healthy
      children. Additionally, 15 adults with KBD and 15 healthy adults were selected
      and divided into 5 KBD vs. control pairs matched according to age and gender,
      with each pair having 3 KBD adults and 3 healthy adults. Total RNA was isolated
      from peripheral blood mononuclear cells (PBMCs) respectively. A total of 367
      target genes were selected based on previous genome-wide gene expression profile
      analysis. Expression levels of the 367 genes were evaluated by customized
      oligonucleotide microarray and the differentially expressed genes were
      identified. Quantitative real-time reverse transcription polymerase chain
      reaction (qRT-PCR) was conducted to validate the microarray data. RESULTS: A
      total of 95 (25.9%) genes in KBD children and 158 (43.1%) genes in KBD adults
      were found to exhibit more than two-fold change in gene expression level relative
      to healthy controls. By comparing differentially expressed genes identified in
      KBD children to those of KBD adults, 42 genes were found to be differentially
      expressed only in KBD children. And 105 genes were found to be differentially
      expressed only in KBD adults. Further, 16 differentially expressed genes common
      to both KBD children and adults were found to be asynchronously expressed in KBD
      children compared to KBD adults. CONCLUSION: Significant differences in gene
      expression pattern were identified between KBD children and KBD adults,
      indicating different molecular mechanisms underlying cartilage lesions of KBD
      children and KBD adults. In addition, bone development-related genes GDF5
      (expression ratio = 2.14+/-0.02) and DIO2 (expression ratio = 0.11+/-0.05) may
      contribute to the development of KBD in children rather than in adults.

PMID- 25072643
TI  - Simple and fast method for iron determination in white and red wines using
      dispersive liquid-liquid microextraction and ultraviolet-visible
      spectrophotometry.
AB  - This work reports the development of a method for Fe extraction in white and red
      wines using dispersive liquid-liquid microextraction (DLLME) and determination by
      ultraviolet-visible spectrophotometry. For optimization of the DLLME method, the
      following parameters were evaluated: type and volume of dispersive (1300 MUL of
      acetonitrile) and extraction (80 MUL of C(2)Cl(4)) solvents, pH (3.0),
      concentration of ammonium pyrrolidinedithiocarbamate (APDC, 500 MUL of 1% m/v
      APDC solution), NaCl concentration (not added), and extraction time. The
      calibration curve was performed using the analyte addition method, and the limit
      of detection and relative standard deviation were 0.2 mg L(-1) and below 7%,
      respectively. The accuracy was evaluated by comparison of results obtained after
      Fe determination by graphite furnace atomic absorption spectrometry, with
      agreement ranging from 94 to 105%. The proposed method was applied for Fe
      determination in white and red wines with concentrations ranging from 1.3 to 4.7
      mg L(-1).

PMID- 25072644
TI  - Faculty development on professionalism and medical ethics: the design,
      development and implementation of Objective Structured Teaching Exercises
      (OSTEs).
AB  - BACKGROUND: As students are expected to develop competency in professionalism and
      medical ethics, faculty are also expected to facilitate medical students'
      learning and understanding of these areas. One of the main challenges to success
      in this domain has been uncertainty of whether or not faculty know the content
      and the methods to teach and assess these competencies. AIM: We used the
      Objective Structured Teaching Exercise (OSTE) format as a faculty development
      tool to train and evaluate faculty on how to teach professionalism and medical
      ethics to students in clinical settings. METHODS: The process for the design,
      development and implementation of OSTEs consisted of five phases: (1) performing
      a literature review and student needs assessment, (2) developing the OSTE cases
      and performance checklists, (3) recruiting and training of standardized students,
      (4) conducting a mock training session and (5) organizing faculty development
      workshops using OSTEs. RESULTS: Twenty clinical faculty members participated in
      one of three half-day OSTE workshops offered. Faculty confidence and attitudes
      about teaching professionalism increased significantly (p < 0.05) from before
      participating in the workshop to afterwards. CONCLUSIONS: Faculty feedback were
      positive stating that the OSTE scenarios were reflective of issues they generally
      encounter while teaching medical students, the information and skills they
      learned from the workshop are important to them as clinical educators, and that
      the information and skills will likely have an impact on the way they teach
      professionalism and ethics in the future.

PMID- 25072645
TI  - Understanding indocyanine green angiography in polypoidal choroidal vasculopathy:
      the group experience with digital fundus photography and confocal scanning laser
      ophthalmoscopy.
AB  - PURPOSE: To evaluate the angiographic features in using fundus camera-based
      versus confocal scanning laser ophthalmoscope (cSLO)-based indocyanine green
      angiography in differentiating polypoidal choroidal vasculopathy (PCV) from
      typical age-related macular degeneration. METHODS: Sixty-five eyes of 44 patients
      with exudative maculopathy due to PCV or typical age-related macular degeneration
      were prospectively imaged with indocyanine green angiography using fundus camera
      and cSLO. Images were graded independently by retinal specialists. The main
      outcome measure was agreement between cSLO and fundus camera for the diagnosis of
      PCV. The rate of detection and area under the receiver operating characteristic
      curve of 7 preselected individual features were also compared. RESULTS: The
      diagnosis of PCV was made with the cSLO system in 36 eyes (55.4%) and typical age
      related macular degeneration in 29 eyes (44.6%), whereas the fundus camera
      diagnosed PCV in 39 eyes (60.0%) and typical age-related macular degeneration in
      26 eyes (40.0%). There was moderate agreement between the two indocyanine green
      angiography systems (Kappa = 0.53). Using cSLO as the gold standard, fundus
      camera has a sensitivity and specificity of 83.3% and 69.0%, respectively.
      Typical nodular appearance was the most commonly detected feature (median, 88.9%
      for cSLO, 80.6% for fundus camera, P = 0.63) and had the highest area under the
      curve for the diagnosis of PCV in both systems (median, 80.2% for cSLO, 73.2% for
      fundus camera, P = 0.13). Confocal scanning laser ophthalmoscope was more
      sensitive in detecting branching vascular network and late hyperfluorescent
      plaque. CONCLUSION: Both systems detected >80% of PCV based on typical nodular
      appearance of polyps. However, the cSLO is superior in detecting additional
      features, particularly branching vascular network.

PMID- 25072646
TI  - Macular and peripapillary spectral domain optical coherence tomography changes in
      sickle cell retinopathy.
AB  - PURPOSE: To assess peripapillary retinal nerve fiber layer, macular ganglion cell
      complex, and total macular thicknesses using spectral domain optical coherence
      tomography on sickle cell disease patients with and without sickle retinopathy.
      METHOD: Nineteen eyes of 11 patients with hemoglobin sickle cell disease, 65 eyes
      of 36 patients with hemoglobin SS disease, and 48 eyes of 24 healthy subjects
      underwent spectral domain optical coherence tomography scanning (RTVue). Eyes of
      patients with sickle cell disease were classified into 3 groups according to
      posterior segment changes: no retinopathy (n = 64), nonproliferative retinopathy
      (n = 12), and proliferative retinopathy (n = 8). RESULTS: The central fovea in
      eyes with proliferative retinopathy was thickened compared with control group,
      sickle cell disease without retinopathy, and nonproliferative retinopathy (P =
      0.004); a difference between proliferative retinopathy and sickle cell disease
      without retinopathy groups was still present after age adjustment (P = 0.014).
      Eyes with proliferative changes showed higher ganglion cell complex focal loss of
      volume compared with control group (P = 0.002), even after age adjustment (P =
      0.004). Thinning of the nasal retinal nerve fiber layer quadrant was observed in
      eyes with proliferative retinopathy (P < 0.001); however, no retinal nerve fiber
      layer thickness difference was observed after age correction (P > 0.05).
      CONCLUSION: Peripheral changes secondary to proliferative sickle retinopathy were
      associated with thinning of macular inner retinal layers and thickening of
      central fovea.

PMID- 25072647
TI  - Effect of topical aqueous suppression on intraocular gas duration after pure
      perfluoropropane injection in nonvitrectomized eyes with retinal detachment.
AB  - PURPOSE: To determine whether topical aqueous suppressants affect the duration of
      pure expansile intraocular gas in nonvitrectomized eyes. METHODS: A prospective
      randomized controlled trial was performed on nonvitrectomized patients undergoing
      retinal detachment repair with scleral buckle or pneumatic retinopexy using 0.3
      mL of 100% perfluoropropane (C3F8) gas tamponade. Eyes were randomly assigned to
      receive topical dorzolamide 2% and timolol 0.5% twice daily postoperatively until
      gas dissolution or to observation. RESULTS: Twenty-one patients met all inclusion
      and exclusion criteria. Twelve were randomized to the control group and nine to
      the dorzolamide-timolol group. In the dorzolamide-timolol group, mean intraocular
      pressure was 17.4 on postoperative Day 1 and 12.5 on postoperative Week 1 (P =
      0.03). In the control group, mean intraocular pressure was 14.5 on postoperative
      Day 1 and 15.1 on postoperative Week 1 (P = 0.73). The mean duration of C3F8 was
      37.8 days in the dorzolamide-timolol group and 40.4 days in the control group (P
      = 0.70). CONCLUSION: Topical aqueous suppression does not seem to have a
      significant effect on the duration of pure expansile intraocular C3F8 in
      nonvitrectomized eyes after pneumatic retinopexy or scleral buckling.

PMID- 25072648
TI  - Intraocular pressure in patients with neovascular age-related macular
      degeneration switched to aflibercept injection after previous anti-vascular
      endothelial growth factor treatments.
AB  - PURPOSE: To assess for change in intraocular pressure (IOP) in neovascular age
      related macular degeneration patients switched to aflibercept after receiving
      previous treatments of intravitreal bevacizumab or ranibizumab. METHODS: This is
      a retrospective chart review of the first 53 patients (53 eyes) treated with at
      least 2 injections of 2 mg in 0.05 mL of aflibercept by March 6, 2013, after at
      least 2 previous injections of 0.5 mg in 0.05 mL of ranibizumab with or without
      previous injections of 1.25 mg in 0.05 mL of bevacizumab. The analysis was
      restricted to the first such sequence within each patient. The last previous anti
      vascular endothelial growth factor injection before the switch to aflibercept was
      ranibizumab in all cases included in the study. Each person served as his or her
      own control. The pre-aflibercept IOP in the before state (treatment with
      bevacizumab or ranibizumab) was the preinjection IOP measure before dilation at
      the visit of the first aflibercept injection. Statistical analysis was performed
      using Microsoft Excel. RESULTS: There were 41 patients who were first treated
      with ranibizumab followed by aflibercept and 12 patients treated with ranibizumab
      and bevacizumab followed by aflibercept. For each of these sequences, IOP in the
      treated eye during treatment with aflibercept (the after state) was computed in 3
      different ways: the first IOP, the last IOP, and the mean IOP for the period when
      treated with aflibercept. The pooled data showed a mean pre-aflibercept (the
      before state) IOP of 14.87 that decreased to a mean first IOP of 14.57, mean last
      IOP of 13.79, and a mean IOP of 14.14 during aflibercept treatment. The inference
      is based on the pooled analysis. The 95% confidence interval for the differences
      (after minus before) were -0.30 (-1.12 to 0.52), -1.08 (-1.83 to -0.32), and 
      0.73 (-1.30 to -0.17) for the first, last, and mean IOPs, respectively. The
      corresponding P values were 0.46 for the first, 0.006 for the last, 0.01 for the
      mean IOP during the aflibercept treatment period. CONCLUSION: Intraocular
      pressure was found to be significantly lower in patients switched to aflibercept
      after previous treatments with ranibizumab and/or bevacizumab. Aflibercept may
      have a more favorable IOP safety profile in patients previously on other anti
      vascular endothelial growth factor treatments.

PMID- 25072649
TI  - Therapeutic outcomes of retinal hemangioblastomas.
AB  - PURPOSE: To report the results of treatments and therapeutic complications of
      retinal hemangioblastomas (RH). METHODS: Retrospective consecutive case series.
      Data from 32 patients (37 eyes) with RH were reviewed for characteristics of RH
      and treatment outcomes. RESULTS: Among 32 patients, we identified 73 RHs in 37
      eyes. At baseline, 24 of 37 eyes (65%) had 20/50 visual acuity or better, 8 eyes
      (22%) had intermediate vision (20/400-20/50), and 5 eyes (13%) had poor vision
      (<=20/400). Seven RHs (9.6%) were located in the juxtapapillary area, and 66 RHs
      (90.4%) were located in peripheral area. Small RHs (54.8%; <0.5 mm in size) were
      treated with laser photocoagulation, moderate-sized RHs (24.7%; 0.5-3.0 mm in
      size) were treated with transpupillary thermotherapy, and large RHs (20.5%; >3.0
      mm in size) were treated with a combination of transpupillary thermotherapy and
      cryotherapy. After treatment, 90% of small RHs regressed, whereas only 67% of
      large RHs regressed (P = 0.044). Peripheral RHs showed better response to
      treatment than juxtapapillary RHs (P = 0.010). Treatment-related complications
      occurred in 5 eyes (14%), and 1-step combination therapy was applied more
      frequently in the complication group (P = 0.048). CONCLUSION: Small RHs in
      peripheral areas may require aggressive treatment because they respond well to
      treatment. In larger RHs, staged treatment could reduce treatment-related
      complications. Transpupillary thermotherapy could be an effective method in tumor
      regression for moderate-to-large-sized RHs showing tumor regression rate of 70%.

PMID- 25072651
TI  - The potential of dental stem cells differentiating into neurogenic cell lineage
      after cultivation in different modes in vitro.
AB  - Trauma or degenerative diseases of the central nervous system (CNS) cause the
      loss of neurons or glial cells. Stem cell transplantation has become a vital
      strategy for CNS regeneration. It is necessary to effectively induce
      nonneurogenic stem cells to differentiate into neurogenic cell lineages because
      of the limited source of neurogenic stem cells, relatively difficult cultivation,
      and ethical issues. Previous studies have found that dental stem cells can be
      used for transplantation therapy. The aim of this study was to explore a better
      inductive mode and time point for dental stem cells to differentiate into neural
      like cells and evaluate a better candidate cell. In this study, dental follicle
      stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical
      papilla (SCAPs) were cultivated in five different modes. The proliferation
      ability, morphology, and expression of neural marker genes were analyzed. Results
      showed that DFSCs showed a higher proliferation potential. The proliferation was
      decreased after cultivation in chemical inductive medium as cultivation modes 3
      and 5. The cells could present neural-like cell morphology after cultivation with
      human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as
      cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in
      mode 4 on the third day was upregulated significantly. In conclusion, our data
      suggested that different dental stem cells exhibited different neural
      differentiation potentials. DFSCs might be the better candidate cell type.
      Furthermore, cultivation mode 4 and timing of the third day may promote
      differentiation into neurogenic cell lineages more effectively before
      transplantation to treat neurological diseases.

PMID- 25072650
TI  - Mitosis gives a brief window of opportunity for a change in gene transcription.
AB  - Cell differentiation is remarkably stable but can be reversed by somatic cell
      nuclear transfer, cell fusion, and iPS. Nuclear transfer to amphibian oocytes
      provides a special opportunity to test transcriptional reprogramming without cell
      division. We show here that, after nuclear transfer to amphibian oocytes, mitotic
      chromatin is reprogrammed up to 100 times faster than interphase nuclei. We find
      that, as cells traverse mitosis, their genes pass through a temporary phase of
      unusually high responsiveness to oocyte reprogramming factors (mitotic
      advantage). Mitotic advantage is not explained by nuclear penetration, DNA
      modifications, histone acetylation, phosphorylation, methylation, nor by salt
      soluble chromosomal proteins. Our results suggest that histone H2A
      deubiquitination may account, at least in part, for the acquisition of mitotic
      advantage. They support the general principle that a temporary access of
      cytoplasmic factors to genes during mitosis may facilitate somatic cell nuclear
      reprogramming and the acquisition of new cell fates in normal development. 

PMID- 25072652
TI  - Serum 25-hydroxyvitamin D and insulin resistance in apparently healthy
      adolescents.
AB  - PURPOSE: Vitamin D deficiency is a common condition that is associated with
      diabetes and insulin resistance. However, the association between vitamin D and
      insulin resistance has not been fully studied, especially in the general
      adolescent population. Therefore, we assessed the association between serum 25
      hydroxyvitamin D [25(OH)D] level and insulin resistance among apparently healthy
      Korean adolescents. METHODS: A total of 260 (135 male and 125 female) adolescents
      in a rural high school were assessed for serum 25(OH)D, fasting plasma glucose,
      and insulin. All of the participants were aged 15 to 16 years old, and without
      known hypertension or diabetes. Serum 25(OH)D was analyzed both as a continuous
      and categorical variable in association with insulin resistance. Insulin
      resistance was estimated by homeostasis model assessment (HOMA-IR). Increased
      insulin resistance was operationally defined as a HOMA-IR value higher than the
      sex-specific 75th percentile. RESULTS: In male adolescents, every 10 ng/ml
      decrease in 25(OH)D level was associated with a 0.25 unit increase in HOMA-IR (p
      = 0.003) after adjusting for age and BMI. Compared to those in the highest
      quartile, male adolescents in the lowest 25(OH)D quartile were at significantly
      higher risk for insulin resistance: unadjusted odds ratio 4.06 (95% CI, 1.26 to
      13.07); age and BMI adjusted odds ratio 3.59 (95% CI, 1.03 to 12.57). However,
      25(OH)D level, either in continuous or categorical measure, was not significantly
      associated with insulin resistance among female adolescents. CONCLUSIONS: This
      study suggests that serum 25(OH)D level may be inversely associated with insulin
      resistance in healthy male adolescents.

PMID- 25072654
TI  - Supramolecular thermoplastic with 0.5 Pa.s melt viscosity.
AB  - Design of materials with polymer-like properties at service temperature but able
      to flow like simple liquids when heated remains one of the important challenges
      of supramolecular chemistry. Combining these antagonistic properties is highly
      desirable to provide durability, processability, and recyclability of materials.
      Here, we explore a new strategy based on polycondensation reactions to design
      supramolecular polymer materials with stress at break above 10 MPa and melt
      viscosity lower than 1 Pa.s. We report the synthesis and rheological and
      mechanical properties (uniaxial tensile tests) of supramolecular polymers based
      on a multiblock polyamide architecture. The flexibility of polycondensation
      reactions made it possible to control the molecular size distribution, the
      strength of hydrogen bonds, and the crystallization of middle and end groups and
      to achieve targeted properties. 

PMID- 25072653
TI  - Synapse density and dendritic complexity are reduced in the prefrontal cortex
      following seven days of forced abstinence from cocaine self-administration.
AB  - Chronic cocaine exposure in both human addicts and in rodent models of addiction
      reduces prefrontal cortical activity, which subsequently dysregulates reward
      processing and higher order executive function. The net effect of this impaired
      gating of behavior is enhanced vulnerability to relapse. Previously we have shown
      that cocaine-induced increases in brain-derived neurotrophic factor (BDNF)
      expression in the medial prefrontal cortex (PFC) is a neuroadaptive mechanism
      that blunts the reinforcing efficacy of cocaine. As BDNF is known to affect
      neuronal survival and synaptic plasticity, we tested the hypothesis that
      abstinence from cocaine self-administration would lead to alterations in neuronal
      morphology and synaptic density in the PFC. Using a novel technique, array
      tomography and Golgi staining, morphological changes in the rat PFC were analyzed
      following 14 days of cocaine self-administration and 7 days of forced abstinence.
      Our results indicate that overall dendritic branching and total synaptic density
      are significantly reduced in the rat PFC. In contrast, the density of thin
      dendritic spines are significantly increased on layer V pyramidal neurons of the
      PFC. These findings indicate that dynamic structural changes occur during cocaine
      abstinence that may contribute to the observed hypo-activity of the PFC in
      cocaine-addicted individuals. 

PMID- 25072655
TI  - High-pressure and theoretical studies reveal significant differences in the
      electronic structure and bonding of magnesium, zinc, and nickel ions in
      metalloporphyrinoids.
AB  - High pressure in combination with optical spectroscopy was used to gain insights
      into the interactions between Mg(2+), Zn(2+), and Ni(2+) ions and macrocyclic
      ligands of porphyrinoid type. In parallel, the central metal ion-macrocycle
      bonding was investigated using theoretical approaches. The symmetry properties of
      the orbitals participating in this bonding were analyzed, and pigment geometries
      and pressure/ligation effects were computed within DFT. Bacteriopheophytin a was
      applied as both a model chelator and a highly specific spectroscopic probe. The
      analysis of solvent and pressure effects on the spectral properties of the model
      Mg(2+), Zn(2+), and Ni(2+) complexes with bacteriopheophytin a shows that various
      chemical bonds are formed in the central pocket, depending on the valence
      configuration of the central metal ion. In addition, the character of this
      bonding depends on symmetry of the macrocyclic system. Since in most cases it is
      not coordinative bonding, these results challenge the conventional view of metal
      ion bonding in such complexes. In (labile) complexes with the main group metals,
      the metal ion-macrocycle interaction is mostly electrostatic. Significantly,
      water molecules are not preferred as a second axial ligand in such complexes,
      mainly due to the entropic constraints. The metal ions with a closed d shell may
      form (stable) complexes with the macrocycle via classical coordination bonds,
      engaging their p and s orbitals. Transition metals, due to the unfilled d shell,
      do form much more stable complexes, because of strong bonding via both
      coordination and covalent interactions. These conclusions are confirmed by DFT
      computations and theoretical considerations, which altogether provide the basis
      to propose a consistent and general mechanism of how the central metal ion and
      its interactions with the core nitrogens govern the physicochemical properties of
      metalloporphyrinoids. 

PMID- 25072656
TI  - TIE: an ability test of emotional intelligence.
AB  - The Test of Emotional Intelligence (TIE) is a new ability scale based on a
      theoretical model that defines emotional intelligence as a set of skills
      responsible for the processing of emotion-relevant information. Participants are
      provided with descriptions of emotional problems, and asked to indicate which
      emotion is most probable in a given situation, or to suggest the most appropriate
      action. Scoring is based on the judgments of experts: professional
      psychotherapists, trainers, and HR specialists. The validation study showed that
      the TIE is a reliable and valid test, suitable for both scientific research and
      individual assessment. Its internal consistency measures were as high as .88. In
      line with theoretical model of emotional intelligence, the results of the TIE
      shared about 10% of common variance with a general intelligence test, and were
      independent of major personality dimensions. 

PMID- 25072657
TI  - Advances in understanding percutaneous coronary intervention pharmacology:
      ischemia, bleeding, the ISAR research group, and a commitment to progress.

PMID- 25072658
TI  - Functional assessment of multivessel coronary artery disease: ischemia-guided
      percutaneous coronary intervention.
AB  - Invasive evaluation and treatment of coronary artery disease (CAD) has
      traditionally been based upon coronary angiography to determine the need for and
      the success of revascularization. However, coronary angiography augmented with
      fractional flow reserve (FFR) creates a paradigm shift, providing a more complete
      functional assessment of coronary lesions. Measuring FFR to identify ischemic
      lesions and guide revascularization results in fewer adverse outcomes, including
      persistent angina, myocardial infarction, and mortality. An ischemic lesion
      identified by FFR is more likely to lead to adverse events when compared with an
      angiographically similar lesion with nonischemic FFR when both are treated
      medically. Although the mechanism explaining this is unclear, it is likely
      multifactorial, including the impact of mechanical forces, upregulation of
      inflammatory mediators, and the amount of distal myocardial tissue at risk. Using
      both anatomic and ischemia-guided assessments (such as the Functional SYNTAX
      Score) aids in the therapeutic decision-making process in patients with
      multivessel CAD. This review focuses on the evidence for FFR-guided management of
      multivessel CAD. 

PMID- 25072659
TI  - Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by
      cardiac fibroblasts through a ROS-STAT3-dependent mechanism.
AB  - Cardiac fibroblasts significantly contribute to diabetes-induced structural and
      functional changes in the myocardium. The objective of the present study was to
      determine the effects of high glucose (alone or supplemented with angiotensin II)
      in the activation of the JAK2/STAT3 pathway and its involvement in collagen I
      production by cardiac fibroblasts. We observed that the diabetic environment 1)
      enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear
      localization of tyrosine phosphorylated STAT3 through a reactive oxygen species
      mediated mechanism, with angiotensin II stimulation further enhancing STAT3
      nuclear accumulation; and 3) stimulated collagen I production. The effects were
      inhibited by depletion of reactive oxygen species or silencing of STAT3 in high
      glucose alone or supplemented with exogenous angiotensin II. Combined, our data
      demonstrate that increased collagen I deposition in the setting of high glucose
      occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our
      results reveal a novel role for STAT3 as a key signaling molecule of collagen I
      production in cardiac fibroblasts exposed to a diabetic environment. 

PMID- 25072661
TI  - Pd nanoparticle concentration dependent self-assembly of Pd@SiO2 nanoparticles
      into leaching resistant microcubes.
AB  - Pd NP concentration guided the self-assembly of core-shell Pd@SiO2 nanoparticles
      (NPs) into microcubes. The Pd NPs were stacked by molten dodecyltrimethylammonium
      bromide (DTAB) to create the SiO2 envelope. The microcubes demonstrated improved
      leaching resistance in heterogeneous catalysis over a conventional porous
      support. 

PMID- 25072660
TI  - On the flow topology inside droplets moving in rectangular microchannels.
AB  - The flow topology in moving microdroplets has a significant impact on the
      behaviour of encapsulated objects and hence on applications of the technology.
      This study reports on a systematic investigation of the flow field inside
      droplets moving in a rectangular microchannel, by means of micro-particle image
      velocimetry (MUPIV). Various water/oil (w/o) fluid mixtures were studied in order
      to elucidate the effects of a number of parameters such as capillary number (Ca),
      droplet geometry, viscosity ratio and interfacial tension. A distinct change in
      flow topology was observed at intermediate Ca ranging from 10(-3) to 10(-1), in
      surfactant-laden droplets, which was attributed primarily to the viscosity ratio
      of the two phases rather than the Marangoni effect expected in such systems. W/o
      droplet systems of lower inner-to-outer viscosity ratios tend to exhibit the well
      known flow pattern characterised by a parabola-like profile in the droplet bulk
      volume, surrounded by two counter rotating recirculation zones on either side of
      the droplet axis. As the viscosity ratio between the two phases is increased, the
      flow pattern becomes more uniform, exhibiting low velocities in the droplet bulk
      volume and higher-reversed velocities along the w/o interface. The Ca and droplet
      geometry had no effect on the observed flow topology change. The study highlights
      the complex, three-dimensional (3D) nature of the flow inside droplets in
      rectangular microchannels and demonstrates the ability to control the droplet
      flow environment by adjusting the viscosity ratio between the two phases. 

PMID- 25072662
TI  - Thyroid storm complicated by bicytopenia and disseminated intravascular
      coagulation.
AB  - PATIENT: Male, 23. FINAL DIAGNOSIS: Thyroid storm. SYMPTOMS: Delirium * diarrhea
      * fever * hypertension * hyperventilation * tachycardia * weight loss.
      MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: Endocrinology and Metabolic.
      OBJECTIVE: Unusual clinical course. BACKGROUND: The clinical presentation of
      thyroid storm includes fever, tachycardia, hypertension, and neurological
      abnormalities. It is a serious condition with a high mortality rate. Furthermore,
      some other complications affect the clinical course of thyroid storm. Although it
      is reported that prognosis is poor when thyroid storm is complicated by
      disseminated intravascular coagulation syndrome (DIC) and leukopenia, reports of
      such cases are rare. CASE REPORT: A 23-year-old man presented with delirium, high
      pyrexia, diarrhea, and weight loss of 18 kg over 2 months. According to the
      criteria of Burch and Wartofsky, he was diagnosed with thyroid storm on the basis
      of his symptom-complex and laboratory data that confirmed the presence of
      hyperthyroidism. Investigations also found leukopenia, thrombocytopenia, and
      disseminated intravascular coagulation, all of which are very rare complications
      of thyroid storm. We successfully treated him with combined therapy including
      anti-thyroid medication, despite leukopenia. CONCLUSIONS: Early diagnosis and
      treatment are essential in ensuring a good outcome for patients with this rare
      combination of medical problems.

PMID- 25072665
TI  - Time resolved analysis of quetiapine and 7-OH-quetiapine in hair using LC/MS-MS.
AB  - Hair analysis is a powerful tool for retrospective drug analysis and has a wide
      application window. This article describes the simultaneous determination and
      quantification of the short-acting atypical antipsychotic drug quetiapine and its
      main metabolite 7-OH quetiapine in hair. A sensitive and accurate method for the
      determination of these two compounds was developed using high-performance liquid
      chromatography coupled to tandem mass spectrometry detection (LC-MS/MS). The
      method was applied to 10 real case samples. For five patients, a time resolved
      hair analysis was done. Results varied from 0.35 ng/mg to 10.21 ng/mg hair for
      quetiapine and from 0.02 ng/mg to 3.19 ng/mg hair for 7-OH-quetiapine.

PMID- 25072666
TI  - The effectiveness of 4 weeks of fundamental movement training on functional
      movement screen and physiological performance in physically active children.
AB  - The effectiveness of fundamental movement training interventions in adolescents
      is not fully understood. The Functional Movement Screen (FMS) may provide means
      of evaluating the effectiveness of such programs alongside traditional tests of
      physiological performance. Twenty-two children completed the FMS, plank, side
      plank, sit and reach, and multistage fitness test. Participants were pair matched
      by total FMS score and assigned to control or intervention. The intervention
      group received a weekly 4 * 30-minute training sessions with an emphasis on
      movement quality, whereas the control group was involved in generic multisport
      activity. A smallest worthwhile effect of 0.2 between-participant SDs was set a
      priori for all measures except total FMS score for which a change of 1 unit was
      chosen. When compared with the control, our intervention had a likely trivial
      effect for FMS score (0.2 Arbitrary Units [AU], 90% confidence limits +/-1.2 AU),
      a very likely small beneficial effect for plank score (87 +/- 55%), but a
      possibly small harmful effect for side plank score (-22 +/- 49%). A likely
      trivial effect was observed for the sit and reach test (0.3 +/- 15%), whereas the
      effect of the training intervention on predicted (Equation is included in full
      text article.)was unclear (-0.3 +/- 11%). Unexpectedly, generic multisport
      activity enhanced both side plank and sit and reach test performances in the
      control group. These results demonstrated that short-term interventions might
      affect specific isolated components of fitness but not FMS performance.

PMID- 25072663
TI  - Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the
      developing heart.
AB  - The origin and developmental mechanisms underlying coronary vessels are not fully
      elucidated. Here we show that myocardium-derived angiopoietin-1 (Ang1) is
      essential for coronary vein formation in the developing heart. Cardiomyocyte
      specific Ang1 deletion results in defective formation of the subepicardial
      coronary veins, but had no significant effect on the formation of intramyocardial
      coronary arteries. The endothelial cells (ECs) of the sinus venosus (SV) are
      heterogeneous population, composed of APJ-positive and APJ-negative ECs. Among
      these, the APJ-negative ECs migrate from the SV into the atrial and ventricular
      myocardium in Ang1-dependent manner. In addition, Ang1 may positively regulate
      venous differentiation of the subepicardial APJ-negative ECs in the heart.
      Consistently, in vitro experiments show that Ang1 indeed promotes venous
      differentiation of the immature ECs. Collectively, our results indicate that
      myocardial Ang1 positively regulates coronary vein formation presumably by
      promoting the proliferation, migration and differentiation of immature ECs
      derived from the SV. 

PMID- 25072667
TI  - A brief review: the implications of iron supplementation for marathon runners on
      health and performance.
AB  - The marathon is considered one of the most demanding endurance events, imposing
      an enormous amount of physiological stress on bodily structures, the metabolic
      machinery, and organ systems. Scientific evidence has conclusively shown that
      marathoners are in need of special nutritional strategies to maintain performance
      and health. Indeed, among competitive athletes, marathoners are at greater risk
      to develop anemia, bone mineral density loss, immunosuppression, and other
      clinical syndromes that may affect performance. Inadequate dietary intake of the
      micronutrient iron has been identified as one key factor in the development of
      the above mentioned anomalies. In fact, iron is one of the few nutrients
      recommended as a supplement by the American College of Sports Medicine (ACSM),
      the Academy of Nutrition and Dietetics (AND), and Dietitians of Canada.
      Therefore, the aim of this review article is to discuss the role of iron on the
      marathoner's health and performance. Special emphasis will be given to the
      physiological mechanisms accounting for the additional iron need in this group of
      athletes and the nutritional strategies intended to counteract iron deficiency.

PMID- 25072668
TI  - Development and assessment of reliability for a sandbag throw conditioning test
      for wrestlers.
AB  - The purpose of this study was to develop and analyze a sport-specific
      conditioning test for wrestling that will incorporate the physiological demands
      of a match. Sixteen D-III collegiate wrestlers performed 2 tests to assess
      physical conditioning. The developed test (sandbag test) used a bag filled with
      sand that was repeatedly thrown over a course of seven 1-minute rounds. Average
      time per throw (T/T) was determined each round. The sandbag test was compared
      with a previously established repeated sprint protocol of maximal effort arm
      cranking on an upper body ergometer (UBE). Mean power output was determined for
      each sprint. Both the UBE test and the sandbag test were compared using
      performance decrement (%fatigue), blood lactate (BLa), and peak heart rate
      (HRpeak) values. Test-retest reliability for the sandbag test was found to be
      almost perfect using T/T (intraclass correlation coefficient, r = 0.96). No
      significant differences in %fatigue were found between the UBE test and the
      sandbag test (p = 0.600), BLa (p = 0.283), and HRpeak (p = 0.214). Further
      analysis by weight class (light-weight class [LWC] and heavy-weight class [HWC])
      found a significant interaction for %fatigue between groups for the sandbag test
      and UBE (p = 0.001), but no interactions were observed for BLa (p = 0.198) or
      HRpeak (p = 0.990). Although no significant differences were found in %fatigue
      between the 2 tests when the data were grouped together, a clear difference was
      found between the LWC and HWC groups only in the sandbag test, indicating that
      this test may be more sensitive than the UBE. Coaches can assess their wrestlers
      with this reliable, inexpensive, and time-efficient sandbag test.

PMID- 25072669
TI  - Free radical scavenging properties of phytofluene and phytoene isomers as
      compared to lycopene: a combined experimental and theoretical study.
AB  - Free radical scavenging properties of Lycopene (LYC), Phytofluene (PF), and
      Phytoene (PE) are studied experimentally, considering the electron transfer
      mechanism and using the ABTS(*+) decolouration assay. Density Functional Theory
      is used to obtain the theoretical UV-visible spectra of ABTS (neutral and cation)
      and to determine the free radical scavenger capacity in terms of the electron
      donor mechanism and the deactivation of singlet oxygen. The experimental data
      agreed very well with the theoretical results. Considering both mechanisms, LYC,
      PF, and PE can be considered good free radical scavengers, with LYC turning out
      to be the best and PE the worst antiradical. However, the triplets that formed
      following the deactivation of singlet oxygen presented similar capacity for
      donating electrons. In the case of triplets, the antiradical capacity of LYC, PF,
      and PE is similar in terms of the electron donor mechanism. Although the results
      indicated that PF and PE are not as effective antiradicals as LYC, which is to be
      expected due to the number of conjugated double bonds, they do present a higher
      antioxidant capacity than expected considering the small number of conjugated
      double bonds. 

PMID- 25072670
TI  - My sleep fest: an autoethnographic short story.

PMID- 25072671
TI  - The effects of experimentally induced adelphophagy in gastropod embryos.
AB  - Adelphophagy, development where embryos grow large by consuming morphologically
      distinct nutritive embryos or their own normal siblings is widespread but
      uncommon among animal phyla. Among invertebrates it is particularly common in
      some families of marine gastropods and segmented worms, but rare or unknown in
      other closely related families. In calyptraeid gastropods phylogenetic analysis
      indicates that adelphophagy has arisen at least 9 times from species with
      planktotrophic larval development. This pattern of frequent parallel evolution of
      adelphophagy suggests that the embryos of planktotrophic species might be
      predisposed to evolve adelphophagy. Here we used embryos of three species of
      planktotrophic calyptraeids, one from each of three major genera in the family
      (Bostrycapulus, Crucibulum, and Crepidula), to answer the following 3 questions:
      (1) Can embryos of species with planktotrophic development benefit, in terms of
      pre-hatching growth, from the ingestion of yolk and tissue from experimentally
      damaged siblings? (2) Does ingestion of this material from damaged siblings
      increase variation in pre-hatching size? and (3) Does this experimentally induced
      adelphophagy alter the allometry between the velum and the shell, increasing
      morphological similarity to embryos of normally adelphophagic species? We found
      an overall increase in shell length and velum diameter when embryos feed on
      damaged siblings within their capsules. There was no detectable increase in
      variation in shell length or velum diameter, or changes in allometry. The overall
      effect of our treatment was small compared to the embryonic growth observed in
      naturally adelphophagic development. However each embryo in our experiment
      probably consumed less than one sibling on average, whereas natural adelphophages
      often each consume 10-30 or more siblings. These results suggest that the ability
      to consume, assimilate, and benefit from yolk and tissue of their siblings is
      widespread across calyptraeids. 

PMID- 25072673
TI  - Creating curricular opportunities for knowledge synthesis.

PMID- 25072674
TI  - Methods and evaluations for simulation debriefing in nursing education.
AB  - Debriefing is the most important aspect of simulated learning, but actual
      debriefing practices are not evidence based or widely known. Expert opinions on
      effective simulation debriefing have been widely published and likely guide
      debriefing in nursing education. However, various terms are used to discuss
      simulation debriefing, making it difficult to distinguish debriefing methods.
      Also, the means for evaluating simulation debriefing are lacking. The purpose of
      this review is to identify and examine methods and evaluations for simulation
      debriefing in the educational setting. Twenty-two methods and seven evaluations
      for simulation debriefing were found. Four areas of differences among methods
      suggested uses, design features, supplemental resources, and means for evaluation
      were demonstrated. This review offers nurse educators and researchers a
      comprehensive, practical examination of the methods and evaluations for
      simulation debriefing in the educational setting, clarifies terminology, and
      describes how the debriefing methods, phases, approaches, elements, and
      evaluations are interrelated.

PMID- 25072675
TI  - Innovative teaching method in emergency response education of undergraduate
      nursing students.

PMID- 25072672
TI  - Using drug combinations to assess potential contributions of non-GABAA receptors
      in the discriminative stimulus effects of the neuroactive steroid pregnanolone in
      rats.
AB  - Neuroactive steroids are increasingly implicated in the development of depression
      and anxiety and have been suggested as possible treatments for these disorders.
      While neuroactive steroids, such as pregnanolone, act primarily at gamma
      aminobutyric acidA (GABAA) receptors, other mechanisms might contribute to their
      behavioral effects and could increase their clinical effectiveness, as compared
      with drugs acting exclusively at GABAA receptors (e.g., benzodiazepines). The
      current study examined the role of non-GABAA receptors, including N-methyl-d
      aspartate (NMDA) and serotonin3 (5-HT3) receptors, in the discriminative stimulus
      effects of pregnanolone. Separate groups of rats discriminated either 3.2mg/kg
      pregnanolone from vehicle or 0.32mg/kg of the benzodiazepine midazolam from
      vehicle while responding under a fixed-ratio 10 schedule for food pellets. When
      administered alone in both groups, pregnanolone and midazolam produced >=80% drug
      lever responding, the NMDA receptor antagonists dizocilpine and phencyclidine
      produced >=60 and >=30% drug-lever responding, respectively, and the 5-HT3
      receptor agonist 1-(m-chlorophenyl)-biguanide (CPBG) and morphine produced <20%
      drug-lever responding up to doses that markedly decreased response rates. When
      studied together, neither dizocilpine, phencyclidine, CPBG nor morphine
      significantly altered the midazolam dose-effect curve in either group. Given that
      CPBG is without effect, it is unlikely that 5-HT3 receptors contribute
      substantially to the discriminative stimulus effects of pregnanolone.
      Similarities across groups in effects of dizocilpine and phencyclidine suggest
      that NMDA receptors do not differentially contribute to the effects of
      pregnanolone. Thus, NMDA and 5-HT3 receptors are not involved in the
      discriminative stimulus effects of pregnanolone. 

PMID- 25072676
TI  - Leaderless organization: active learning strategy in a concept-based curriculum.

PMID- 25072678
TI  - Follicular mucinosis associated with nonlymphoid skin conditions.
AB  - BACKGROUND: Follicular mucinosis coexisting with lymphoproliferative disorders
      has been thoroughly debated. However, it has been rarely reported in association
      with inflammatory disorders. METHODS: Thirteen cases have been retrieved, and
      those with cutaneous lymphoma or alopecia mucinosa were excluded. RESULTS:
      Follicular mucinosis was found in the setting of squamous cell carcinoma,
      seborrheic keratosis, simple prurigo, acne vulgaris, dextrometorphan-induced
      phototoxicity, polymorphous light eruption (2 cases), insect bite (2 cases), tick
      bite, discoid lupus erythematosus, drug-related vasculitis, and demodecidosis.
      Unexpectedly, our observations revealed a preponderating accumulation of mucin
      related to photo-exposed areas, sun-associated dermatoses, and histopathologic
      solar elastosis. The amount of mucin filling the follicles apparently correlated
      with the intensity of perifollicular inflammatory infiltrate, which was present
      in all cases. The concurrence of dermal interstitial mucin was found in 7 cases
      (54%). CONCLUSIONS: The concurrence of interstitial dermal mucinosis or the
      potential role of both ultraviolet radiation and the perifollicular inflammatory
      infiltrates in its pathogenesis deserves further investigations. Precise
      recognition and understanding of this distinctive, reactive histological pattern
      may prevent our patients from unnecessary diagnostic and therapeutic strategies.

PMID- 25072677
TI  - Factors affecting noncompliance with buprenorphine maintenance treatment.
AB  - BACKGROUND: The current study aimed to identify risk factors for treatment
      noncompliance in a sample of veterans receiving buprenorphine/naloxone for an
      opioid use disorder. METHODS: Records from all patients who are currently or had
      previously been maintained on buprenorphine in the buprenorphine maintenance
      treatment program at the Atlanta VA Medical Center during the years 2006 to 2013
      were evaluated. Of the 209 patients treated in the clinic between 2006 and 2013,
      140 were excluded from the study because they did not have a call-back done at
      the time of data collection. Thus, 69 patient charts were selected for review.
      RESULTS: The multiple linear regression analysis of the predictable variables for
      noncompliance with the buprenorphine pill count showed that positive urine drug
      screen (UDS) for marijuana, benzodiazepines, and being a smoker (F = 3.08; P =
      0.03) are significantly associated with noncompliance with buprenorphine pill
      count.Also, the multiple linear regression analysis of the predictable variables
      for noncompliance with the buprenorphine pill count showed that the psychiatric
      comorbidity independently (F = 4.88; P = 0.03) is significantly associated with
      noncompliance with buprenorphine pill count. CONCLUSIONS: Patients found to be
      noncompliant were more likely to suffer from comorbid psychiatric illness.
      Patients who tested positive for benzodiazepines or cannabis were more likely to
      be noncompliant with treatment. Although the rate of noncompliance (inaccurate
      pill count) was high, patients were still found to be taking their prescribed
      buprenorphine as evidenced by positive UDS for buprenorphine/norbuprenorphine. In
      addition, our sample had a high rate of negative UDS screens for opioids and
      cocaine.

PMID- 25072679
TI  - Braided pattern in a dermatofibrosarcoma protuberans: a potential mimicker of
      neural neoplasms.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous slow-growing
      tumor of intermediate malignancy. Different histological variants of DFSP have
      been described, depending on cellular and stromal peculiarities. Here, we report
      the histological features of a DFSP in which cells were frequently arrayed in
      cords and fascicles that were interweaved, conforming a peculiar braided pattern.
      This finding might pose difficulties in the differential diagnosis with neural
      neoplasms and expands the morphological spectrum of DFSP.

PMID- 25072680
TI  - CD30 positive atypical lymphocytes in perniosis: a potential histopathologic
      pitfall in a benign condition.
AB  - In classical clinical perniosis (chilblains), the presence of atypical
      lymphocytes with immunohistochemical staining positive for CD30 is unusual and
      rarely reported. Here we report 2 cases of clinical perniosis, one in a 16-year
      old girl and another in a 67-year-old woman. The biopsies revealed lymphocytic
      infiltrates, papillary dermal edema, and atypical cells highlighted with a CD30
      immunohistochemical stain. Our cases demonstrate the importance of
      clinicopathologic correlation in the assessment of CD30 positive lymphocytes in
      benign nonneoplastic conditions. Dermatopathologists must be aware of this
      potential histologic pattern in perniosis to prevent misdiagnosis and
      overtreatment of this condition.

PMID- 25072681
TI  - Vascular leg ulcers: histopathologic study of 293 patients.
AB  - Vascular leg ulcers remain a challenge for the modern health care, and a
      systematic pathological study on this kind of lesions has not been reported so
      far. A total of 293 consecutive white patients with chronic leg ulcers (present
      for a minimum of 6 months and up to several years) referred to the Wound Care
      Unit (Dermatology, University of Bologna) between March 2008 and June 2011.
      Thirty-four patients affected by other than vascular ulcers, neoplastic or
      inflammatory conditions, were excluded. The remaining 259 patients affected by
      vascular leg ulcers were enrolled in this study. Assessment of the patients
      general health, skin biopsy, and vascular Doppler of the lower limbs were
      performed to determine the etiology and to formulate an appropriate management
      plan, whereas 2 punch biopsies of 3 mm were performed on the border and on the
      bed of each ulcer. Doppler evaluation showed the presence of vascular hemodynamic
      impairment in 259 patients. Of these, 181 (69.9%) patients were affected by
      venous insufficiency, 58 (22.4%) by venous and arterial insufficiency, and 20
      (7.7%) by arterial insufficiency. Histopathologic features revealed significant
      differences, thus, reflecting the clinicopathologic correlation with the
      underlying hemodynamic impairments. In conclusion, histopathologic and
      hemodynamic data correlation could provide the basis for future analysis of leg
      ulcers pathogenesis and may improve treatment protocols. We should underline that
      this observational study represents a single-institute experience and that larger
      series are needed to confirm our observations.

PMID- 25072682
TI  - Neutrophilic Fixed Drug Eruption.
AB  - Fixed drug eruption (FDE) is a cutaneous reaction to a medication that recurs in
      the same fairly localized site with each exposure to the offending drug. The
      classical histopathologic findings in FDE consist of an interface dermatitis with
      predominantly lymphocytic inflammatory cell infiltrate. An unusual case of FDE in
      a 27-year-old pregnant woman who presented with widespread lesions and a
      predominantly neutrophilic infiltrate on histopathologic examination is reported.

PMID- 25072683
TI  - Hyperplasia and Hypertrophy of Pacinian Corpuscles: A Case Report.
AB  - The proliferation of Pacinian corpuscles is a rare benign lesion that occurs
      frequently in the fingers of hands, with the only clinical sign of pain when a
      drastic temperature change happens. A case of an extremely rare lesion in which
      we observed hypertrophy and hyperplasia of Pacinian corpuscles has been reported.

PMID- 25072684
TI  - Elastoderma: Case Report and Literature Review.
AB  - Elastoderma is a rare cutaneous condition, which clinically presents as an
      acquired laxity and decreased recoil of skin. It is histologically characterized
      by an increase of pleomorphic and fragmented elastic fibers in the superficial
      dermis. A case of a 61-year-old woman with wrinkled lax skin on the anterior and
      lateral aspects of her neck was reported. Microscopic examination revealed an
      accumulation of fragmented curled elastic fibers in the dermis. This is the fifth
      reported case of elastoderma. 

PMID- 25072685
TI  - Primary Cutaneous Gamma-Delta T-Cell Lymphoproliferative Disorder in a 3-Year-Old
      Boy.
AB  - Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a rare disorder,
      constituting less than 1% of primary cutaneous lymphomas. Most cases occur in
      adults and may present as plaques or nodules with ulceration. Here we describe an
      unusual case of PCGD-TCL in a 3-year-old boy who presented with asymptomatic
      subcutaneous nodules. To our knowledge, this report represents one of the
      youngest reported patients with gamma-delta lymphoma/lymphoproliferative
      disorder. In addition, our patient has an indolent clinical presentation with
      greater than 1 year clinical follow-up. Because gamma-delta T-cell lymphomas are
      exceedingly rare in children, we acknowledge that the clinical course/outcome in
      young patients is still unclear. We hope to add to the recognition that PCGD-TCLs
      demonstrate a wide clinical spectrum of disease with relatively indolent
      presentations in some cases. 

PMID- 25072686
TI  - Nodular Melanoma Arising in a Large Segmental Speckled Lentiginous Nevus.

PMID- 25072687
TI  - Changes of epidermal thickness in vitiligo.
AB  - The stratum corneum and epidermal pigmentation have protective roles against
      ultraviolet radiation. Because vitiligo skin lacks melanocytes and has no
      potential to produce pigment, some studies suggested that the epidermis in
      vitiligo skin is thicker than in normal skin. However, only a few studies
      investigated epidermal thickness changes in vitiligo, and some of these had
      relatively small sample sizes. Thus, this study aimed to compare epidermal
      thickness between vitiligo skin and adjacent normal-appearing skin in a large
      cohort. Photos of hematoxylin and eosin-stained slides of vitiligo skin and
      adjacent normal-appearing skin were taken under a microscope. The thicknesses of
      the stratum corneum, viable epidermis, and full epidermis were then measured by a
      computerized image analyzer. A total of 206 patients (412 sections) were
      included. There were significant differences between vitiligo skin and adjacent
      normal-appearing skin in the thickness of the stratum corneum (P = 0.009), viable
      epidermis (P = 0.001), and total epidermis (P = 0.001). An analysis comparing
      skin biopsied from a sun-exposed area versus a sun-protected area showed that the
      stratum corneum, viable epidermis, and total epidermis were significantly thicker
      in vitiligo skin than in normal-appearing skin in sun-exposed areas (P < 0.05),
      but not in sun-protected areas. We revealed that the epidermis was thicker in
      vitiligo skin than in normal-appearing skin, especially on sun-exposed skin, and
      that this may represent a photoprotective role compensating for absent
      pigmentation.

PMID- 25072688
TI  - Athlete's nodule in a figure skater: an unusual presentation.
AB  - Sports-related acquired connective tissue nevus or "athlete's nodule" has been
      reported under a variety of different names. The lesion develops in response to
      activity causing chronic or repetitive low-grade pressure or irritation activity,
      which is often a component of athletic training. A case of "athlete's nodule" in
      a figure skater has been reported. Our case demonstrates the typical
      histopathologic findings of deposition of normal-appearing collagen bundles
      arranged haphazardly within the dermis as described in previous reports.
      Additionally, results of CD34, colloidal iron, and elastic tissue staining have
      been described. The macular clinical presentation with the absence of significant
      epidermal change is a unique presentation of athletic nodule. It is the goal of
      the authors to create increased awareness among pathologists and clinicians in
      identifying these lesions and to expand the clinical presentation to include
      nonprotuberant lesions.

PMID- 25072689
TI  - Cutaneous keratocyst and steatocystoma unified as sebaceous duct cyst, a
      hamartoma resembling the sebaceous duct.

PMID- 25072690
TI  - Indolent subtype acral lentiginous melanoma with long radial growth phase: a
      dermatopathological pitfall.

PMID- 25072691
TI  - On Steatocystoma, Sebaceous Duct Cyst, Isthmic-Anagenic Cyst, and CK19.

PMID- 25072692
TI  - A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an
      HDV Ribozyme and a Short Hairpin RNA.
AB  - Antisense-based molecules targeting HIV-1 RNA have the potential to be used as
      part of gene or drug therapy to treat HIV-1 infection. In this study, HIV-1 RNA
      was screened to identify more conserved and accessible target sites for ribozymes
      based on the hepatitis delta virus motif. Using a quantitative screen for effects
      on HIV-1 production, we identified a ribozyme targeting a highly conserved site
      in the Gag coding sequence with improved inhibitory potential compared to our
      previously described candidates targeting the overlapping Tat/Rev coding
      sequence. We also demonstrate that this target site is highly accessible to short
      hairpin directed RNA interference, suggesting that it may be available for the
      binding of antisense RNAs with different modes of action. We provide evidence
      that this target site is structurally conserved in diverse viral strains and that
      it is sufficiently different from the human transcriptome to limit off-target
      effects from antisense therapies. We also show that the modified hepatitis delta
      virus ribozyme is more sensitive to a mismatch in its target site compared to the
      short hairpin RNA. Overall, our results validate the potential of a new target
      site in HIV-1 RNA to be used for the development of antisense therapies. 

PMID- 25072693
TI  - BET-independent MLV-based Vectors Target Away From Promoters and Regulatory
      Elements.
AB  - Stable integration in the host genome renders murine leukemia virus (MLV)-derived
      vectors attractive tools for gene therapy. Adverse events in otherwise successful
      clinical trials caused by proto-oncogene activation due to vector integration
      hamper their application. MLV and MLV-based vectors integrate near strong
      enhancers, active promoters, and transcription start sites (TSS) through specific
      interaction of MLV integrase (IN) with the bromodomain and extra-terminal (BET)
      family of proteins, accounting for insertional mutagenesis. We identified a BET
      interaction motif in the C-terminal tail of MLV IN conserved among
      gammaretroviruses. By deletion of this motif or a single point mutation
      (INW390A), BET-independent MLV (BinMLV) were engineered. BinMLV vectors carrying
      INW390A integrate at wild-type efficiency, with an integration profile that no
      longer correlates with BET chromatin distribution nor with the traditional
      markers of MLV integration. In particular, BinMLV vector integration associated
      less with oncogene TSS compared to the MLV vectors currently used in clinical
      trials. Together, these findings open perspectives to increase the biosafety of
      gammaretroviral vectors for gene therapy. 

PMID- 25072694
TI  - Antisense-mediated Exon Skipping Decreases Tau Protein Expression: A Potential
      Therapy For Tauopathies.
AB  - In Alzheimer's disease, progressive supranuclear palsy, and a number of other
      neurodegenerative diseases, the microtubule associated protein tau aggregates to
      form intracellular neurofibrillary tangles and glial tangles, abnormal structures
      that are part of disease pathogenesis. Disorders with aggregated tau are called
      tauopathies. Presently, there are no disease-modifying treatments for this
      disease class. Tau is encoded by the MAPT gene. We propose that reducing MAPT
      expression and thus the amount of tau protein made could prevent aggregation, and
      potentially be an approach to treat tauopathies. We tested 31 morpholinos,
      complementary to the sense strand of the MAPT gene to identify oligonucleotides
      that can downregulate MAPT expression and reduce the amount of tau protein
      produced. Oligonucleotides were tested in human neuroblastoma cell lines SH-SY5Y
      and IMR32. We identified several morpholinos that reduced MAPT mRNA expression up
      to 50% and tau protein levels up to ~80%. The two most potent oligonucleotides
      spanned the 3' boundary of exons 1 and 5, masking the 5'-splice sites of these
      exons. Both morpholinos induced skipping of the targeted exons. These in vitro
      findings were confirmed in mice transgenic for the entire human MAPT gene and
      that express human tau protein. These studies demonstrate the feasibility of
      using modified oligonucleotides to alter tau expression. 

PMID- 25072695
TI  - Indole synthesis from N-allenyl-2-iodoanilines under mild conditions mediated by
      samarium(II) diiodide.
AB  - A novel method for indole skeleton synthesis under mild conditions mediated by
      samarium(ii) diiodide has been developed. The reaction of N-allenyl-2-iodoaniline
      derivatives with SmI2 in the presence of HMPA and i-PrOH at 0  degrees C afforded
      indole derivatives in high yields. 

PMID- 25072696
TI  - NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation.
AB  - CD40, a member of tumour necrosis factor receptor (TNFR) superfamily, has a
      pivotal role in B-cell-mediated immunity through various effector pathways
      including AKT kinase, but the signal transduction of CD40-meidated AKT activation
      is poorly understood. Here we report that the neural precursor cell expressed
      developmentally downregulated protein 4 (NEDD4), homologous to E6-AP Carboxyl
      Terminus family E3 ubiquitin ligase, is a novel component of the CD40 signalling
      complex. It has a key role in CD40-mediated AKT activation and is involved in
      modulating immunoglobulin class switch through regulating the expression of
      activation-induced cytidine deaminase. NEDD4 constitutively interacts with CD40
      and mediates K63-linked ubiquitination of TNFR-associated factor3 (TRAF3). The
      ubiquitination of TRAF3 by NEDD4 is critical for CD40-mediated AKT activation.
      Thus, NEDD4 is a previously unknown component of the CD40 signalling complex
      necessary for AKT activation. 

PMID- 25072697
TI  - The yeast histone chaperone hif1p functions with RNA in nucleosome assembly.
AB  - BACKGROUND: Hif1p is an H3/H4-specific histone chaperone that associates with the
      nuclear form of the Hat1p/Hat2p complex (NuB4 complex) in the yeast Saccharomyces
      cerevisiae. While not capable of depositing histones onto DNA on its own, Hif1p
      can act in conjunction with a yeast cytosolic extract to assemble nucleosomes
      onto a relaxed circular plasmid. RESULTS: To identify the factor(s) that function
      with Hif1p to carry out chromatin assembly, multiple steps of column
      chromatography were carried out to fractionate the yeast cytosolic extract.
      Analysis of partially purified fractions indicated that Hif1p-dependent chromatin
      assembly activity resided in RNA rather than protein. Fractionation of isolated
      RNA indicated that the chromatin assembly activity did not simply purify with
      bulk RNA. In addition, the RNA-mediated chromatin assembly activity was blocked
      by mutations in the human homolog of Hif1p, sNASP, that prevent the association
      of this histone chaperone with histone H3 and H4 without altering its
      electrostatic properties. CONCLUSIONS: These results suggest that specific RNA
      species may function in concert with histone chaperones to assemble chromatin.

PMID- 25072698
TI  - Allethrin induces oxidative stress, apoptosis and calcium release in rat
      testicular carcinoma cells (LC540).
AB  - Over the years, pyrethroids, including D-allethrin, are widely used for domestic
      and agricultural purposes and are found to be toxic to many organ systems
      including the male reproductive system. However, the molecular mechanisms of
      allethrin toxicity are not well understood. In this study, we demonstrate that
      allethrin exhibited a dose-dependent cytotoxicity on Leydig cell carcinoma cells
      (LC540) and isolated primary Leydig cells with an IC50 of 125 MUM and 59 MUM
      respectively. Cytotoxicity was associated with generation of reactive oxygen
      species, increased lipid peroxidation and alterations in antioxidant enzyme
      status. Morphological analyses of LC540 cells treated with allethrin revealed the
      presence of apoptotic bodies. Using flow cytometry, we observed that the number
      of cells that displayed early apoptotic features and entering into G0 phase of
      cell cycle increased significantly with loss of mitochondrial membrane potential.
      The levels of p53 mRNA and cleaved PARP-1 protein were increased, whereas BCL-2,
      pro-Caspase-3 and PARP-1 were decreased. Allethrin induced apoptosis was
      associated with voltage gated calcium channel mediated intracellular calcium
      release. Results of our study demonstrate that allethrin toxicity in the male
      reproductive tract may involve Leydig cell apoptotic death.

PMID- 25072699
TI  - Association analysis of stem rust resistance in U.S. winter wheat.
AB  - Stem rust has become a renewed threat to global wheat production after the
      emergence and spread of race TTKSK (also known as Ug99) and related races from
      Africa. To elucidate U.S. winter wheat resistance genes to stem rust, association
      mapping was conducted using a panel of 137 lines from cooperative U.S. winter
      wheat nurseries from 2008 and simple sequence repeat (SSR) and sequence tagged
      site (STS) markers across the wheat genome. Seedling infection types were
      evaluated in a greenhouse experiment using six U.S. stem rust races (QFCSC,
      QTHJC, RCRSC, RKQQC, TPMKC and TTTTF) and TTKSK, and adult plant responses to
      bulked U.S. races were evaluated in a field experiment. A linearization algorithm
      was used to convert the qualitative Stakman scale seedling infection types for
      quantitative analysis. Association mapping successfully detected six known stem
      rust seedling resistance genes in U.S. winter wheat lines with frequencies: Sr6
      (12%), Sr24 (9%), Sr31 (15%), Sr36 (9%), Sr38 (19%), and Sr1RSAmigo (8%). Adult
      plant resistance gene Sr2 was present in 4% of lines. SrTmp was postulated to be
      present in several hard winter wheat lines, but the frequency could not be
      accurately determined. Sr38 was the most prevalent Sr gene in both hard and soft
      winter wheat and was the most effective Sr gene in the adult plant field test.
      Resistance to TTKSK was associated with nine markers on chromosome 2B that were
      in linkage disequilibrium and all of the resistance was attributed to the
      Triticum timopheevii chromosome segment carrying Sr36. Potential novel rust
      resistance alleles were associated with markers Xwmc326-203 on 3BL, Xgwm160-195
      and Xwmc313-225 on 4AL near Sr7, Xgwm495-182 on 4BL, Xwmc622-147 and Xgwm624-146
      on 4DL, and Xgwm334-123 on 6AS near Sr8. Xwmc326-203 was associated with adult
      plant resistance to bulked U.S. races and Xgwm495-182 was associated with
      seedling resistance to TTKSK. 

PMID- 25072702
TI  - Elastic free energy drives the shape of prevascular solid tumors.
AB  - It is well established that the mechanical environment influences cell functions
      in health and disease. Here, we address how the mechanical environment influences
      tumor growth, in particular, the shape of solid tumors. In an in vitro tumor
      model, which isolates mechanical interactions between cancer tumor cells and a
      hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft
      reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor
      shape robustly occurs when the tumors grow in hydrogels that are stiffer than the
      tumors, but when they grow in more compliant hydrogels they remain closer to
      spherical in shape. Using large scale, nonlinear elasticity computations we show
      that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor
      hydrogel system. Having eliminated a number of other candidate explanations, we
      hypothesize that minimization of the elastic free energy is the reason for
      predominance of the experimentally observed ellipsoidal shape. This result may
      hold significance for explaining the shape progression of early solid tumors in
      vivo and is an important step in understanding the processes underlying solid
      tumor growth. 

PMID- 25072703
TI  - Impact of acellular mucin pools on survival in patients with complete
      pathological response to neoadjuvant treatment in rectal cancer.
AB  - BACKGROUND: Rarely, patients with pathological complete response (PCR) after
      neoadjuvant chemoradiotherapy demonstrate acellular mucin pools. The prognostic
      significance of this finding is controversial. The objective of this study was to
      determine impact of acellular mucin pools on disease free and overall survival in
      patients with complete pathological response to neoadjuvant chemoradiotherapy in
      rectal cancer. METHODS: One hundred and seventy two patients received neoadjuvant
      chemoradiotherapy for rectal cancer and underwent surgery. Patients were divided
      into two groups based on presence of acellular mucin pools. Locoregional
      failures, distant failures and deaths were compared. Expected 5 year disease free
      and overall survival was calculated. RESULTS: Median follow-up was 36(4-94)
      months. Complete pathological response was identified in 35(20.3%) patients. Of
      these, 12(34.2%) had acellular mucin pools in resected specimen. Majority of
      mucin negative tumors were moderately differentiated (78% vs 25%) (P = 0.005).
      Median overall survival for mucin positive and mucin negative tumors was 4(1.3
      5.7) and 3.3(0.1-6.3) years respectively. Expected 5 year disease free and
      overall survival for mucin positive and mucin negative tumors was 73% and 89% (P
      = 0.1) and 75% and 87% (P = 0.4). CONCLUSION: Acellular mucin pools in rectal
      cancer following a PCR to neoadjuvant treatment do not impact survival.

PMID- 25072704
TI  - A personalized adhesion prevention strategy: E. Arslan, T. Talih, B. Oz, B.
      Halaclar, K. Caglayan, M. Sipahi, Comparison of lovastatin and hyaluronic
      acid/carboxymethyl cellulose on experimental created peritoneal adhesion model in
      rats, Int. J. Surg. 12 (2) (2014) 120-124.

PMID- 25072706
TI  - Enhanced catalytic activity of polyethylenedioxythiophene towards tri-iodide
      reduction in DSSCs via 1-dimensional alignment using hollow carbon nanofibers.
AB  - Here, we report a highly conducting 1-dimensionally (1-D) aligned
      polyethylenedioxythiophene (PEDOT) along the inner and outer surfaces of a hollow
      carbon nanofiber (CNF) and its application as a counter electrode in a dye
      sensitized solar cell (DSSC). The hybrid material (CP-25) displays a conversion
      efficiency of 7.16% compared to 7.30% for the standard Pt counter electrode,
      4.48% for bulk PEDOT and 5.56% for CNF. The enhanced conversion efficiency of CP
      25 is attributed to the accomplishment of high conductivity and surface area of
      PEDOT through the 1-D alignment compared to its bulk counterpart. Reduced charge
      transfer resistance and high conductivity of CP-25 could be proven by cyclic
      voltammetry, impedance analysis and Tafel experiments. Further, through a long
      term stability test involving efficiency profiling for 20 days, it is observed
      that CP-25 possesses excellent durability compared to the bulk PEDOT. 

PMID- 25072707
TI  - Controlling the thermomechanical behavior of nanoparticle/polymer films.
AB  - We show that the mesoscale (~200 nm) thermomechanical properties of polymer
      nanocomposites formed from silica nanoparticles (NPs) and poly(2-vinylpyridine)
      (P2VP) critically depend on their interfacial structure, which can be controlled
      by the casting solvent. The composite films are solvent cast from either pyridine
      (PYR) or methylethylketone (MEK), with uniform NP spatial distribution obtained
      in both cases. In the films cast from MEK, our previous work has shown that a
      bound layer of P2VP is formed at the NP surfaces, while no such bound layer is
      formed when PYR is used as the casting solvent. In PYR as-cast films, Brillouin
      light scattering reveals a single acoustic phonon with its longitudinal sound
      velocity increasing with NP loading. This implies a homogeneous mixture of the NP
      and the polymer on the mesoscopic scales for all compositions examined. However,
      in the MEK as-cast films, two longitudinal and two transverse acoustic phonons
      are observed at NP loadings above ~20 wt % (or ~11 vol %), reminiscent of two
      metastable microscopic phases. The dense microphase is attributed to the bridging
      of NPs by P2VP chains, whereas for the softer medium, we conjecture that there
      exists an interfacial lower density P2VP layer whose longitudinal sound velocity
      barely changes with NP loading. These solvent-induced differences in the
      (elastic) mechanical behavior disappear upon thermal annealing, suggesting that
      these nanocomposite interfacial structures in the as-cast state (far from
      equilibrium) locally approach equilibrium (i.e., near equilibrium after
      annealing). Consistent with these conclusions, the abrupt decrease of the
      longitudinal sound velocity with temperature occurs at a single glass transition
      temperature for the annealed nanocomposites irrespective of the casting solvent
      used, which assumes only a slightly higher (~5 K at 45 wt % or ~29 vol %) value
      than that in bulk P2VP. The results emphasize the important role of solvent in
      determining the interfacial structure of nanocomposites, which can be used to
      tailor their thermomechanical behavior. 

PMID- 25072705
TI  - The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does
      not influence packaging of a functional RNA genome.
AB  - The viral integrase (IN) is an essential protein for HIV-1 replication. IN
      inserts the viral dsDNA into the host chromosome, thereby aided by the cellular
      co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described:
      allosteric IN inhibitors (ALLINIs). Although designed to interfere with the IN
      LEDGF/p75 interaction to block HIV DNA integration during the early phase of HIV
      1 replication, the major impact was surprisingly found on the process of virus
      maturation during the late phase, causing a reverse transcription defect upon
      infection of target cells. Virus particles produced in the presence of an ALLINI
      are misformed with the ribonucleoprotein located outside the virus core. Virus
      assembly and maturation are highly orchestrated and regulated processes in which
      several viral proteins and RNA molecules closely interact. It is therefore of
      interest to study whether ALLINIs have unpredicted pleiotropic effects on these
      RNA-related processes. We confirm that the ALLINI BI-D inhibits virus replication
      and that the produced virus is non-infectious. Furthermore, we show that the wild
      type level of HIV-1 genomic RNA is packaged in virions and these genomes are in a
      dimeric state. The tRNAlys3 primer for reverse transcription was properly placed
      on this genomic RNA and could be extended ex vivo. In addition, the packaged
      reverse transcriptase enzyme was fully active when extracted from virions. As the
      RNA and enzyme components for reverse transcription are properly present in
      virions produced in the presence of BI-D, the inhibition of reverse transcription
      is likely to reflect the mislocalization of the components in the aberrant virus
      particle. 

PMID- 25072708
TI  - Identification of novel regulatory cholesterol metabolite, 5-cholesten, 3beta,25
      diol, disulfate.
AB  - Oxysterol sulfation plays an important role in regulation of lipid metabolism and
      inflammatory responses. In the present study, we report the discovery of a novel
      regulatory sulfated oxysterol in nuclei of primary rat hepatocytes after
      overexpression of the gene encoding mitochondrial cholesterol delivery protein
      (StarD1). Forty-eight hours after infection of the hepatocytes with recombinant
      StarD1 adenovirus, a water-soluble oxysterol product was isolated and purified by
      chemical extraction and reverse-phase HPLC. Tandem mass spectrometry analysis
      identified the oxysterol as 5-cholesten-3beta, 25-diol, disulfate (25HCDS), and
      confirmed the structure by comparing with a chemically synthesized compound.
      Administration of 25HCDS to human THP-1-derived macrophages or HepG2 cells
      significantly inhibited cholesterol synthesis and markedly decreased lipid levels
      in vivo in NAFLD mouse models. RT-PCR showed that 25HCDS significantly decreased
      SREBP-1/2 activities by suppressing expression of their responding genes,
      including ACC, FAS, and HMG-CoA reductase. Analysis of lipid profiles in the
      liver tissues showed that administration of 25HCDS significantly decreased
      cholesterol, free fatty acids, and triglycerides by 30, 25, and 20%,
      respectively. The results suggest that 25HCDS inhibits lipid biosynthesis via
      blocking SREBP signaling. We conclude that 25HCDS is a potent regulator of lipid
      metabolism and propose its biosynthetic pathway. 

PMID- 25072709
TI  - Inferring directions of evolution from patterns of variation: the legacy of
      Sergei Meyen.
AB  - In the era of the extended evolutionary synthesis, which no longer considers
      natural selection as the only leading factor of evolution, it is meaningful to
      revisit the legacy of biologists who discussed the role of alternative factors.
      Here we analyze the evolutionary views of Sergei Meyen (1935-1987), a
      paleobotanist who argued that the theory of evolution should incorporate a
      "nomothetical" approach which infers the laws of morphogenesis (i.e., form
      generation) from the observed patterns of variation in living organisms and in
      the fossil records. Meyen developed a theory of "repeated polymorphic sets"
      (RPSs), which he applied consistently to describe inter-organism variation in
      populations, intra-organism variation of metameric organs, variation of
      abnormalities, heterotopy, changes during embryo development, and inter-species
      variation within evolutionary lineages. The notion of RPS assumes the active
      nature of organisms that possess hidden morphogenic and behavioral capacities.
      Meyen's theory is compatible with Darwin's natural selection; however, Meyen
      emphasized the importance of other forms of selection (e.g., selection of
      developmental trajectories, habitats, and behaviors) in choosing specific
      elements from the RPS. Finally, Meyen developed a new typological concept of
      time, where time represents variability (i.e., change) of real objects such as
      living organisms or geological formations. 

PMID- 25072711
TI  - Modeling of human exposure to benzene in urban environments.
AB  - Urban areas characterized by high spatial and temporal variability in air
      pollution levels require implementation of comprehensive approaches to address
      exposure of individuals. The main objective of this study was to implement a
      quantitative assessment of individual exposure to benzene in urban environments.
      For this purpose, ExPOSITION model based on a global positioning system (GPS)
      tracking approach was applied to estimate individual exposure in different
      microenvironments. The current investigation provides an application example and
      validation of the modeling approach against personal and biological exposure
      measurements collected during the measurements campaign. The probabilistic
      approach using the Johnson system of distributions was implemented to
      characterize variability of indoor concentrations. The results obtained for daily
      average individual exposure to benzene corresponded to mean levels of 1.6 and 0.8
      2.7 MUg/m(3) in terms of 5th-95th percentiles. Validation of the model results
      against several personal exposure samples collected for the selected individuals
      revealed a Pearson's correlation coefficient of .66. This modeling approach
      explicitly addressed the temporal and spatial variability in the exposure and
      established a source-receptor relationship. 

PMID- 25072712
TI  - Aspergillus flavus contamination in two Portuguese wastewater treatment plants.
AB  - Filamentous fungi from genus Aspergillus were previously detected in wastewater
      treatment plants (WWTP) as being Aspergillus flavus (A. flavus), an important
      toxigenic fungus producing aflatoxins. This study aimed to determine occupational
      exposure adverse effects due to fungal contamination produced by A. flavus
      complex in two Portuguese WWTP using conventional and molecular methodologies.
      Air samples from two WWTP were collected at 1 m height through impaction method.
      Surface samples were collected by swabbing surfaces of the same indoor sites.
      After counting A. flavus and identification, detection of aflatoxin production
      was ensured through inoculation of seven inoculates in coconut-milk agar. Plates
      were examined under long-wave ultraviolet (UV; 365 nm) illumination to search for
      the presence of fluorescence in the growing colonies. To apply molecular methods,
      air samples were also collected using the impinger method. Samples were collected
      and collection liquid was subsequently used for DNA extraction. Molecular
      identification of A. flavus was achieved by real-time polymerase chain reaction
      (RT-PCR) using the Rotor-Gene 6000 qPCR detection system (Corbett). Among the
      Aspergillus genus, the species that were more abundant in air samples from both
      WWTP were Aspergillus versicolor (38%), Aspergillus candidus (29.1%), and
      Aspergillus sydowii (12.7%). However, the most commonly species found on surfaces
      were A. flavus (47.3%), Aspergillus fumigatus (34.4%), and Aspergillus sydowii
      (10.8%). Aspergillus flavus isolates that were inoculated in coconut agar medium
      were not identified as toxigenic strains and were not detected by RT-PCR in any
      of the analyzed samples from both plants. Data in this study indicate the need
      for monitoring fungal contamination in this setting. Although toxigenic strains
      were not detected from A. flavus complex, one cannot disregard the eventual
      presence and potential toxicity of aflatoxins. 

PMID- 25072713
TI  - Water quality concerns due to forest fires: polycyclic aromatic hydrocarbons
      (PAH) contamination of groundwater from mountain areas.
AB  - Water quality alterations due to forest fires may considerably affect aquatic
      organisms and water resources. These impacts are cumulative as a result of
      pollutants mobilized from fires, chemicals used to fight fire, and postfire
      responses. Few studies have examined postfire transport into water resources of
      trace elements, including the polycyclic aromatic hydrocarbons (PAH), which are
      organic pollutants produced during combustion and are considered carcinogenic and
      harmful to humans. PAH are also known to adversely affect survival, growth, and
      reproduction of many aquatic species. This study assessed the effects of forest
      wildfires on groundwater from two mountain regions located in protected areas
      from north and central Portugal. Two campaigns to collect water samples were
      performed in order to measure PAH levels. Fifteen of 16 studied PAH were found in
      groundwater samples collected at burned areas, most of them at concentrations
      significantly higher than those found in control regions, indicating aquifer
      contamination. The total sum of PAH in burned areas ranged from 23.1to 95.1 ng/L
      with a median of 62.9 ng/L, which is one- to sixfold higher than the average
      level measured in controls (16.2 ng/L). In addition, in control samples, the
      levels of light PAH with two to four rings were at higher levels than heavy PAH
      with five or six rings, thus showing a different profile between control and
      burned sites. The contribution of wildfires to groundwater contamination by PAH
      was demonstrated, enabling a reliable assessment of the impacts on water quality
      and preparation of scientifically based decision criteria for postfire forest
      management practices. 

PMID- 25072714
TI  - Identification and levels of airborne fungi in Portuguese primary schools.
AB  - Several studies found associations between exposure to airborne fungi and
      allergy, infection, or irritation. This study aimed to characterize airborne
      fungi populations present in public primary schools in Porto, Portugal, during
      winter through quantification and identification procedures. Fungal concentration
      levels and identification were obtained in a total of 73 classrooms. The AirIdeal
      portable air sampler was used in combination with chloramphenicol malt extract
      agar. Results showed a wide range of indoor fungi levels, with indoor
      concentrations higher than outdoors. The most prevalent fungi found indoors were
      Penicillium sp. (>70%) and Cladosporium sp. As evidence indicates that indoor
      fungal exposures plays a role in asthma clinical status, these results may
      contribute to (1) promoting and implementing public health prevention programs
      and (2) formulating recommendations aimed at providing healthier school
      environments. 

PMID- 25072715
TI  - Ultrafine particles in ambient air of an urban area: dose implications for
      elderly.
AB  - Due to their detrimental effects on human health, the scientific interest in
      ultrafine particles (UFP) has been increasing, but available information is far
      from comprehensive. Compared to the remaining population, the elderly are
      potentially highly susceptible to the effects of outdoor air pollution. Thus,
      this study aimed to (1) determine the levels of outdoor pollutants in an urban
      area with emphasis on UFP concentrations and (2) estimate the respective dose
      rates of exposure for elderly populations. UFP were continuously measured over 3
      weeks at 3 sites in north Portugal: 2 urban (U1 and U2) and 1 rural used as
      reference (R1). Meteorological parameters and outdoor pollutants including
      particulate matter (PM10), ozone (O3), nitric oxide (NO), and nitrogen dioxide
      (NO2) were also measured. The dose rates of inhalation exposure to UFP were
      estimated for three different elderly age categories: 64-70, 71-80, and >81
      years. Over the sampling period levels of PM10, O3 and NO2 were in compliance
      with European legislation. Mean UFP were 1.7 * 10(4) and 1.2 * 10(4)
      particles/cm(3) at U1 and U2, respectively, whereas at rural site levels were 20
      70% lower (mean of 1 *10(4) particles/cm(3)). Vehicular traffic and local
      emissions were the predominant identified sources of UFP at urban sites. In
      addition, results of correlation analysis showed that UFP were meteorologically
      dependent. Exposure dose rates were 1.2- to 1.4-fold higher at urban than
      reference sites with the highest levels noted for adults at 71-80 yr, attributed
      mainly to higher inhalation rates. 

PMID- 25072716
TI  - Effects of exposure to particles and ozone on hospital admissions for
      cardiorespiratory diseases in SetuBal, Portugal.
AB  - In recent years, the adverse health effects attributed to air pollution have been
      a focus of intense study. Exposure to pollutants such as airborne particulate
      matter (PM) and ozone (O3) has been associated with increases in morbidity and
      mortality due to respiratory and cardiovascular diseases. The aim of this study
      was to determine a correlation between particles (PM10, PM2.5) and O3 with
      hospital admissions in Setubal, a densely populated Portuguese urban region that
      coexists with a heavy industrial area. A database with daily air quality and
      hospital admission data over 5 years (2005-2009) was assembled and associations
      were investigated by ordinary least squares linear regression. Results showed
      positive significant associations between PM10 and respiratory diseases for ages
      below 14 yr and above 64 yr, and between PM2.5 and respiratory diseases for ages
      above 64 yr. 

PMID- 25072717
TI  - Characterization of the toxicological effects of aminocarb on rats:
      hematological, biochemical, and histological analyses.
AB  - Aminocarb is a widely applied carbamate insecticide with action of controlling
      pests such as Lepidoptera and Coleoptera. In this study, subchronic effects on
      Wistar rats were investigated using hematological, biochemical, and histological
      techniques. Rats were exposed orally at sublethal levels of 10, 20, or 40 mg/kg
      body weight (groups A, B, and C, respectively) for 14 d. Hematological results
      revealed no statistical differences after 1 d of exposure but significant
      reduction in white blood cells detected after 7 d of exposure in group C, as well
      as, in all treated groups after 14 d of exposure. Biochemical data showed a
      decrease of acetylcholinesterase activity in all groups after 1 d of exposure
      with a return to normal after 7 and 14 d. Significant increase in alkaline
      phosphatase activity of rats exposed to aminocarb was noted after 7 d of
      treatment. The levels of triglycerides were also significantly decreased. The
      present investigation also showed a significant increase in content of serum urea
      and creatinine in animals from group A (14 d), and from groups B and C (7 and 14
      d). Histological results demonstrated hemorrhagic focus on hepatic and renal
      parenchyma in all exposed groups. Taken together, the attained results were dose
      dependent and indicated adverse effects of aminocarb on hepatic and renal
      functions, as well as on immune responsiveness at sublethal tested doses. 

PMID- 25072718
TI  - Levels and spatial distribution of airborne chemical elements in a heavy
      industrial area located in the north of Spain.
AB  - The adverse health effects of airborne particles have been subjected to intense
      investigation in recent years; however, more studies on the chemical
      characterization of particles from pollution emissions are needed to (1) identify
      emission sources, (2) better understand the relative toxicity of particles, and
      (3) pinpoint more targeted emission control strategies and regulations. The main
      objective of this study was to assess the levels and spatial distribution of
      airborne chemical elements in a heavy industrial area located in the north of
      Spain. Instrumental and biomonitoring techniques were integrated and analytical
      methods for k0 instrumental neutron activation analysis and particle-induced x
      ray emission were used to determine element content in aerosol filters and
      lichens. Results indicated that in general local industry contributed to the
      emissions of As, Sb, Cu, V, and Ni, which are associated with combustion
      processes. In addition, the steelwork emitted significant quantities of Fe and Mn
      and the cement factory was associated with Ca emissions. The spatial distribution
      of Zn and Al also indicated an important contribution of two industries located
      outside the studied area. 

PMID- 25072719
TI  - Determination of airborne nanoparticles in elderly care centers.
AB  - According to numerous studies, airborne nanoparticles have a potential to produce
      serious adverse human health effects when deposited into the respiratory tract.
      The most important parts of the lung are the alveolar regions with their enormous
      surface areas and potential to transfer nanoparticles into the blood stream.
      These effects may be potentiated in case of the elderly, since this population is
      more susceptible to air pollutants in general and more to nanoparticles than
      larger particles. The main goal of this investigation was to determine the
      exposure of institutionalized elders to nanoparticles using Nanoparticle Surface
      Area Monitor (NSAM) equipment to calculate the deposited surface area (DSA) of
      nanoparticles into elderly lungs. In total, 193 institutionalized individuals
      over 65 yr of age were examined in four elderly care centers (ECC). The occupancy
      daily pattern was achieved by applying a questionnaire, and it was concluded that
      these subjects spent most of their time indoors, including the bedroom and living
      room, the indoor microenvironments with higher prevalence of elderly occupancy.
      The deposited surface area ranged from 10 to 46 MUm(2)/cm(3). The living rooms
      presented significantly higher levels compared with bedrooms. Comparing PM10
      concentrations with nanoparticles deposited surface area in elderly lungs, it is
      conceivable that living rooms presented the highest concentration of PM10 and
      were similar to the highest average DSA. The temporal distribution of DSA was
      also assessed. While data showed a quantitative fluctuation in values in
      bedrooms, high peaks were detected in living rooms. 

PMID- 25072720
TI  - Assessment of genotoxic effects in nurses handling cytostatic drugs.
AB  - Several antineoplastic drugs have been classified as carcinogens by the
      International Agency for Research on Cancer (IARC) on the basis of
      epidemiological findings, animal carcinogenicity data, and outcomes of in vitro
      genotoxicity studies. 5-Fluorouracil (5-FU), which is easily absorbed through the
      skin, is the most frequently used antineoplastic agent in Portuguese hospitals
      and therefore may be used as an indicator of surface contamination. The aims of
      the present investigation were to (1) examine surface contamination by 5-FU and
      (2) assess the genotoxic risk using cytokinesis-block micronucleus assay in
      nurses from two Portuguese hospitals. The study consisted of 2 groups: 27 nurses
      occupationally exposed to cytostatic agents (cases) and 111 unexposed individuals
      (controls). Peripheral blood lymphocytes (PBL) were collected in order to measure
      micronuclei (MN) in both groups. Hospital B showed a higher numerical level of
      contamination but not significantly different from Hospital A. However; Hospital
      A presented the highest value of contamination and also a higher proportion of
      contaminated samples. The mean frequency of MN was significantly higher in
      exposed workers compared with controls. No significant differences were found
      among MN levels between the two hospitals. The analysis of confounding factors
      showed that age is a significant variable in MN frequency occurrence. Data
      suggest that there is a potential genotoxic damage related to occupational
      exposure to cytostatic drugs in oncology nurses. 

PMID- 25072721
TI  - Individual exposure to air pollutants in a Portuguese urban industrialized area.
AB  - Industrial development from the second half of the 20th century coupled with
      population growth and concentration in urban areas has accentuated the concern
      for potential effects and impacts from air pollutant emissions on environmental
      and human health. This study examined the Estarreja region, an urban area that
      has one of the largest chemical complexes in Portugal, a complex that was
      recently under expansion. In the scope of the INSPIRAR project, individual daily
      exposure of a group of individuals to particulate matter of 10 MUm aerodynamic
      diameter (PM10) and nitrogen dioxide (NO2) in two phases was determined using a
      microenvironmental approach. In this context, personal daily activity profiles of
      individuals were established for their normal routine by personal interviews.
      These profiles enabled determination of where each individual was at each moment
      of the day. Utilizing this information with hourly air quality maps simulated
      with URBAIR air quality model and indoor/outdoor relationships, it was possible
      to calculate personal daily exposure of each individual to air pollutants.
      Results from the analysis of daily activity profiles showed a high level of
      sedentariness of this population and long durations spent indoors. The studied
      individuals displayed high personal PM10 and NO2 exposure variability. Data
      demonstrated possible error when a single concentration measurement was assumed
      as a proxy of exposure. In general, no significant differences were found between
      the two population groups, indicating that workers of the chemical complex were
      not exposed to a greater extent to PM10 and NO2 than the general population
      working in the same area. 

PMID- 25072722
TI  - Indoor and outdoor biomonitoring using lichens at urban and rural primary
      schools.
AB  - Monitoring particulate matter (PM) and its chemical constituents in classrooms is
      a subject of special concern within the scientific community in order to control
      and minimize child exposure. Regulatory sampling methods have presented several
      limitations in their application to larger number of classrooms due to
      operational and financial constraints. Consequently, passive sampling
      methodologies using filters were developed for indoor sampling. However, such
      methodologies could not provide parallel information for outdoors, which is
      important to identify pollution sources and assess outdoor contribution to the
      indoors. Therefore, biomonitoring with transplanted lichens, a technique usually
      applied for outdoor studies, was used both indoor and outdoor of classrooms.
      Three main objectives were proposed, to (i) characterize simultaneously indoor
      and outdoor of classrooms regarding inorganic air pollutants, (ii) investigate
      spatial patterns of lichen conductivity, and (iii) assess pollution sources that
      contribute to a poor indoor air quality in schools. Lichens Flavoparmelia
      caperata were transplanted to indoor and outdoor of classrooms for 59 d. After
      exposure, electric conductivity of lichens leachate was measured to evaluate
      lichen vitality and cell damage. Outdoors lichen conductivity was higher near the
      main highways, and indoors there was great variability in levels, which indicates
      different emissions sources and different ventilation patterns. Chemical content
      of lichens was assessed by instrumental neutron activation analysis (INAA), and
      As, Br, Ca, Ce, Co, Cr, Cs, Eu, Fe, Hf, K, La, Na, Rb, Sb, Sc, Sm, Sr, Ta, Th,
      Yb, and Zn were determined. Element accumulation, crustal enrichment factors, and
      spatial variability of elements were analyzed and contaminants from anthropogenic
      sources, such as traffic (As, Sb, and Zn) and indoor chalk (Ca) found. Classrooms
      with potential indoor air quality problems were identified by presenting higher
      accumulations of inorganic pollutants in exposed biomonitors. 

PMID- 25072723
TI  - Effects of naproxen on cell proliferation and genotoxicity in MG-63 osteosarcoma
      cell line.
AB  - The purpose of this study was to determine the efficacy of naproxen, a
      nonsteroidal anti-inflammatory drug, on the MG-63 human osteosarcoma cell line.
      MG-63 cells were exposed to naproxen in a wide range of concentrations of 0.03,
      0.05, 0.1, 0.42, 0.83, and 1.67 mg/ml for 72 h. The activity of naproxen was
      assessed by the following assays: cell morphology; 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide (MTT) method; terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) assay; comet assay; and
      acridine orange and monodansylcadaverine (MDC) staining. Naproxen exerted a
      significant inhibitory effect on MG-63 cell proliferation, in a concentration
      dependent manner, in all treatment groups compared with untreated cells. An
      increase in frequency of DNA damage, apoptotic bodies, apoptotic cells, and
      autophagic vacuoles was observed in MG-63-treated cells. Although future studies
      are needed, these findings suggest that naproxen may lead to improvements in
      treatment of patients with osteosarcoma. 

PMID- 25072724
TI  - Emission of nanoparticles during friction stir welding (FSW) of aluminium alloys.
AB  - Friction stir welding (FSW) is now well established as a welding process capable
      of joining some different types of metallic materials, as it was (1) found to be
      a reliable and economical way of producing high quality welds, and (2) considered
      a "clean" welding process that does not involve fusion of metal, as is the case
      with other traditional welding processes. The aim of this study was to determine
      whether the emission of particles during FSW in the nanorange of the most
      commonly used aluminum (Al) alloys, AA 5083 and AA 6082, originated from the Al
      alloy itself due to friction of the welding tool against the item that was being
      welded. Another goal was to measure Al alloys in the alveolar deposited surface
      area during FSW. Nanoparticles dimensions were predominantly in the 40- and 70-nm
      range. This study demonstrated that microparticles were also emitted during FSW
      but due to tool wear. However, the biological relevance and toxic manifestations
      of these microparticles remain to be determined. 

PMID- 25072725
TI  - Environmental and ventilation assessment in Child Day Care Centers in Porto: the
      ENVIRH Project.
AB  - Children attending day care centers (CDCC) have been reported to be more prone to
      infectious diseases when compared with those cared for at home, and are exposed
      to conditions that may increase the risk of allergies and asthma. Several studies
      revealed that consequences of poor ventilation conditions include high levels of
      carbon dioxide (CO2) and many other indoor pollutants commonly detected in
      schools. Nine child day care centers were selected randomly to participate in
      this study. Fifty-two classrooms were assessed for chemical, biological,
      physical, and allergen parameters in spring and winter seasons in these nine CDCC
      located in Porto, Portugal. Outdoor measurements were also conducted for
      comparison. Our results indicated that (i) particulate matter (PM10) median
      levels were above the national reference levels, both by classroom type and by
      season; (ii) TVOC kindergarten peak values may raise some concern; (iii) CO2 was
      present at high median and maximum levels during spring and winter assessment in
      both nurseries and kindergartens classrooms; (iv) total bacteria concentrations
      were 57- and 52-fold higher in the nursery and kindergarten than outdoors,
      respectively, for the spring season; (v) winter and spring median predicted mean
      vote (PMV) indices were between "neutral" (0) and "slightly cool" (<= -1) in the
      thermal sensation scale for comfort situations (-2 to 2) for both types of
      classrooms; (vi) there were significant differences for both PMV and predicted
      percentage of dissatisfied (PPD) indices by season; and (vii) CO2, total
      bacteria, and gram-negative bacteria were associated with low airflow rates.
      These data will help to evaluate the effectiveness of current building operation
      practices in child day care centers regarding indoor air quality and respiratory
      health. 

PMID- 25072726
TI  - Biological air contamination in elderly care centers: geria project.
AB  - Indoor air quality (IAQ) affects health particularly in susceptible individuals
      such as the elderly. It has been estimated that the older population spends
      approximately 19-20 h/d indoors, and the majority of the elderly spend all of
      their time indoors in elderly care centers (ECC). Older individuals may be
      particularly at risk of exposure to detrimental effects from pollutants, even at
      low concentrations, due to common and multiple underlying chronic diseases that
      increase susceptibility. This study, aimed to assess the impact of indoor
      biological agents in 22 ECC located in Porto, was conducted during summer and
      winter from November 2011 to August 2013 at a total of 141 areas within dining
      rooms, drawing rooms, medical offices, and bedrooms (including the bedridden).
      Air sampling was carried out with a microbiological air sampler (Merck MAS-100)
      and using tryptic soy agar for bacteria and malt extract agar for fungi. The
      results obtained were compared with the recently revised Portuguese standards. In
      winter, mean fungi concentration exceeded reference values, while bacteria
      concentrations were within the new standards in both seasons. The main fungi
      species found indoors were Cladosporium (73%) in summer and Penicillium (67%) in
      winter. Aspergillus fumigatus, Aspergillus niger, and Aspergillus flavus, known
      potential pathogenic/toxigenic species, were also identified. Although the
      overall rate and mean values of bacteria and fungi found in ECC indoor air met
      Portuguese legislation, some concern is raised by the presence of pathogenic
      microorganisms. Simple measures, like opening windows and doors to promote air
      exchange and renewal, may improve effectiveness in enhancing IAQ. 

PMID- 25072727
TI  - Mercury-resistant bacteria from salt marsh of Tagus Estuary: the influence of
      plants presence and mercury contamination levels.
AB  - Mercury (Hg) contamination of aquatic systems has been recognized as a global,
      serious problem affecting both wildlife and humans. High levels of Hg, in
      particular methylmercury (MeHg), were detected in surface sediments of Tagus
      Estuary. MeHg is neurotoxic and its concentration in aquatic systems is dependent
      upon the relative efficiency of reduction, methylation, and demethylation
      processes, which are mediated predominantly by the microbial community, in
      particular mercury-resistant (HgR) bacteria. Plants in contaminated ecosystems
      are known to take up Hg via plant roots. Therefore, the aims of this study were
      to (1) isolate and characterize HgR bacteria from a salt marsh of Tagus Estuary
      (Rosario) and (2) determine HgR bacteria levels in the rhizosphere and,
      consequently, their influence in metal cycling. To accomplish this objective,
      sediments samples were collected during the spring season in an area colonized by
      Sacocornia fruticosa and Spartina maritima and compared with sediments without
      plants. From these samples, 13 aerobic HgR bacteria were isolated and
      characterized morphologically, biochemically, and genetically, and susceptibility
      to Hg compounds, Hg(2+), and MeHg was assessed by determination of minimal
      inhibitory concentration (MIC). Genetically, the mer operon was searched by
      polymerase chain reaction (PCR) and 16S rRNA sequencing was used for bacterial
      identification. Results showed that the isolates were capable of growing in the
      presence of high Hg concentration with MIC values for HgCl2 and MeHgCl in the
      ranges of 1.7-4.2 MUg/ml and 0.1-0.9 MUg/ml, respectively. The isolates from
      sediments colonized with Sacocornia fruticosa displayed higher resistance levels
      compared to ones colonized with Spartina maritima. Bacteria isolates showed
      different capacity of Hg accumulation but all displayed Hg volatilization
      capabilities (20-50%). Mer operon was found in two isolates, which genetically
      confirmed their capability to convert Hg compounds by reducing them to Hg(0).
      Thus, these results are the first evidence of the relevance of interaction
      between bacteria and plants in Hg cycling in Tagus Estuary. 

PMID- 25072728
TI  - Characterization of fungal communities in house dust samples collected from
      central Portugal-a preliminary survey.
AB  - House dust is a repository and concentrator of many chemical and biological
      agents including fungi. Considering that dust acts as a long-term reservoir of
      airborne fungi and that cumulative exposure is more relevant to potential health
      problems than single-day or short-term exposure, characterization of fungal
      communities in dust samples is of paramount importance. In the present study, the
      fungal composition of Portuguese house dust samples was determined. A total of 28
      samples were obtained from vacuum cleaner deposits from households located in
      central Portugal. DNA was extracted from dust samples and fungal communities were
      analyzed using a culture-independent polymerase chain reaction (PCR)- denaturing
      gradient gel electrophoresis (DGGE) approach. Cultural analyses were also
      performed in order to identify the viable fungi species present in selected
      samples. Fungal diversity, reported as the number of operational taxonomic units
      (OTU), varied between 9 and 56 OTU. This analysis of viable fungi showed that
      Aspergillus was the most abundant genus, followed by Penicillium, Mucor, and
      Rhizomucor. Trichoderma, Chrysosporium, Fusarium, Rhizopus, and Stachybotrys were
      found in a limited number of houses. Our results demonstrated that dust is, in
      fact, home for a diverse and heterogeneous fungal community and that some of the
      species found are known allergic agents with severe negative impacts on human
      health. 

PMID- 25072729
TI  - Applicability of in vitro methods to study patulin bioaccessibility and its
      effects on intestinal membrane integrity.
AB  - In human health risk assessment, ingestion of food is considered a major route of
      exposure to many contaminants, although the total amount of an ingested
      contaminant (external dose) does not always reflect the quantity available for
      the body (internal dose). In this study, two in vitro methods were applied to
      study bioaccessibility and intestinal membrane integrity of cells exposed to
      patulin, a mycotoxin with significant public health risk. Seven artificially
      contaminated fruit juices were assayed in the presence or absence of a standard
      meal, showing a significant difference for bioaccessibility values between
      contaminated samples alone (mean 27.65 +/- 13.50%) and combinations with a
      standard meal (mean 7.89 +/- 4.03%). Different concentrations of patulin (PAT)
      and cysteine (CYS) (protector agent) were assayed in Caco-2 cells monolayers. At
      95 MUM, PAT produced a marked decrease in transepithelial electrical resistance
      (TEER). This effect was significantly reduced when 400 MUM and 4000 MUM CYS was
      added to the cells. Combined use of in vitro digestion models with other
      techniques using intestinal cell lines, such as in vitro intestinal absorption
      models that use Caco-2 cells, may offer a more comprehensive model of what is
      occurring during digestion and absorption processes. The study of beneficial
      effects of protective agents would also be enhanced. 

PMID- 25072730
TI  - Experimental and theoretical investigations of energy transfer and hydrogen-bond
      breaking in small water and HCl clusters.
AB  - Water is one of the most pervasive molecules on earth and other planetary bodies;
      it is the molecule that is searched for as the presumptive precursor to
      extraterrestrial life. It is also the paradigm substance illustrating ubiquitous
      hydrogen bonding (H-bonding) in the gas phase, liquids, crystals, and amorphous
      solids. Moreover, H-bonding with other molecules and between different molecules
      is of the utmost importance in chemistry and biology. It is no wonder, then, that
      for nearly a century theoreticians and experimentalists have tried to understand
      all aspects of H-bonding and its influence on reactivity. It is somewhat
      surprising, therefore, that several fundamental aspects of H-bonding that are
      particularly important for benchmarking theoretical models have remained
      unexplored experimentally. For example, even the binding strength between two gas
      phase water molecules has never been determined with sufficient accuracy for
      comparison with high-level electronic structure calculations. Likewise, the
      effect of cooperativity (nonadditivity) in small H-bonded networks is not known
      with sufficient accuracy. An even greater challenge for both theory and
      experiment is the description of the dissociation dynamics of H-bonded small
      clusters upon acquiring vibrational excitation. This is because of the long
      lifetimes of many clusters, which requires running classical trajectories for
      many nanoseconds to achieve dissociation. In this Account, we describe recent
      progress and ongoing research that demonstrates how the combined and
      complementary efforts of theory and experiment are enlisted to determine bond
      dissociation energies (D0) of small dimers and cyclic trimers of water and HCl
      with unprecedented accuracy, describe dissociation dynamics, and assess the
      effects of cooperativity. The experimental techniques rely on IR excitation of H
      bonded X-H stretch vibrations, measuring velocity distributions of fragments in
      specific rovibrational states, and determining product state distributions at the
      pair-correlation level. The theoretical methods are based on high-level ab initio
      potential energy surfaces used in quantum and classical dynamical calculations.
      We achieve excellent agreement on D0 between theory and experiments for all of
      the clusters that we have compared, as well as for cooperativity in ring trimers
      of water and HCl. We also show that both the long-range and the repulsive parts
      of the potential must be involved in bond breaking. We explain why H-bonds are so
      resilient and hard to break, and we propose that a common motif in the breaking
      of cyclic trimers is the opening of the ring following transfer of one quantum of
      stretch excitation to form open-chain structures that are weakly bound. However,
      it still takes many vibrational periods to release one monomer fragment from the
      open-chain structures. Our success with water and HCl dimers and trimers led us
      to embark on a more ambitious project: studies of mixed water and HCl small
      clusters. These clusters eventually lead to ionization of HCl and serve as
      prototypes of acid dissociation in water. Measurements and calculations of such
      ionizations are yet to be achieved, and we are now characterizing these systems
      by adding monomers one at a time. We describe our completed work on the HCl-H2O
      dimer and mention our recent theoretical results on larger mixed clusters.

PMID- 25072731
TI  - Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives
      for contraception.
AB  - BACKGROUND: The avoidance of menstruation through continuous or extended (greater
      than 28 days) administration of combination hormonal contraceptives (CHCs) has
      gained legitimacy through its use in treating endometriosis, dysmenorrhea, and
      menstruation-associated symptoms. Avoidance of menstruation through extended or
      continuous use of CHCs for reasons of personal preference may have additional
      advantages to women, including improved compliance, greater satisfaction, fewer
      menstrual symptoms, and less menstruation-related absenteeism from work or
      school. OBJECTIVES: To determine the differences between continuous or extended
      cycle CHCs (pills, patch, ring) in regimens of greater than 28 days of active
      hormone compared with traditional cyclic dosing (21 days of active hormone and 7
      days of placebo, or 24 days of active hormones and 4 days of placebo). Our
      hypothesis was that continuous or extended-cycle CHCs have equivalent efficacy
      and safety but improved bleeding profiles, amenorrhea rates, adherence,
      continuation, participant satisfaction, and menstrual symptoms compared with
      standard cyclic CHCs. SEARCH METHODS: We searched computerized databases
      (Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, POPLINE, LILACS)
      for trials using continuous or extended CHCs (oral contraceptives, contraceptive
      ring and patch) during the years 1966 to 2013. We also searched the references in
      review articles and publications identified for inclusion in the protocol.
      Investigators were contacted regarding additional references. SELECTION CRITERIA:
      All randomized controlled trials in any language comparing continuous or extended
      cycle (greater than 28 days of active hormones) versus traditional cyclic
      administration (21 days of active hormones and 7 days of placebo, or 24 days of
      active hormones and 4 days of placebo) of CHCs for contraception. DATA COLLECTION
      AND ANALYSIS: Titles and abstracts identified from the literature searches were
      assessed for potential inclusion. Data were extracted onto data collection forms
      and then entered into RevMan 5. Peto odds ratios with 95% confidence intervals
      were calculated for all outcomes for dichotomous outcomes. Weighted mean
      difference was calculated for continuous outcomes. The trials were critically
      appraised by examining the following factors: study design, blinding,
      randomization method, group allocation concealment, exclusions after
      randomization, loss to follow-up, and early discontinuation. Because the included
      trials did not have a standard treatment (type of CHC formulation, route of
      delivery, or time length for continuous dosing), we could not aggregate data into
      meta-analysis. MAIN RESULTS: Twelve randomized controlled trials met our
      inclusion criteria. Study findings were similar between 28-day and extended or
      continuous regimens in regard to contraceptive efficacy (i.e., pregnancy rates)
      and safety profiles. When compliance was reported, no difference between 28-day
      and extended or continuous cycles was found. Participants reported high
      satisfaction with both dosing regimens, but this was not an outcome universally
      studied. Overall discontinuation and discontinuation for bleeding problems were
      not uniformly higher in either group. The studies that reported menstrual
      symptoms found that the extended or continuous group fared better in terms of
      headaches, genital irritation, tiredness, bloating, and menstrual pain. Eleven
      out of the twelve studies found that bleeding patterns were either equivalent
      between groups or improved with extended or continuous cycles over time.
      Endometrial lining assessments by ultrasound and/or endometrial biopsy were done
      in some participants and were all normal after cyclic or extended CHC use.
      AUTHORS' CONCLUSIONS: The 2014 update yielded four additional trials but
      unchanged conclusions. Evidence from existing randomized control trials comparing
      continuous or extended-cycle CHCs (greater than 28 days of active combined
      hormones) to traditional cyclic dosing (21 days of active hormone and 7 days of
      placebo, or 24 days of active hormone and 4 days of placebo) is of good quality.
      However, the variations in type of hormones and time length for extended-cycle
      dosing make a formal meta-analysis impossible. Future studies should choose a
      previously described type of CHC and dosing regimen. More attention needs to be
      directed towards participant satisfaction, continuation, and menstruation
      associated symptoms.

PMID- 25072732
TI  - Intense sperm-mediated sexual conflict promotes reproductive isolation in
      Caenorhabditis nematodes.
AB  - Conflict between the sexes over reproductive interests can drive rapid evolution
      of reproductive traits and promote speciation. Here we show that inter-species
      mating between Caenorhabditis nematodes sterilizes maternal individuals. The
      principal effectors of male-induced harm are sperm cells, which induce sterility
      and shorten lifespan by displacing conspecific sperm, invading the ovary, and
      sometimes breaching the gonad to infiltrate other tissues. This sperm-mediated
      harm is pervasive across species, but idiosyncrasies in its magnitude implicate
      both independent histories of sexually antagonistic coevolution within species
      and differences in reproductive mode (self-fertilizing hermaphrodites versus
      females) in determining its severity. Consistent with this conclusion, in
      androdioecious species the hermaphrodites are more vulnerable, the males more
      benign, or both. Patterns of assortative mating and a low incidence of invasive
      sperm occurring with conspecific mating are indicative of ongoing intra-specific
      sexual conflict that results in inter-species reproductive incompatibility. 

PMID- 25072734
TI  - Clinical evaluation of 262 osseointegrated implants placed in sites grafted with
      calcium phosphosilicate putty: a retrospective study.
AB  - Along with the widespread use of dental implants, regenerative procedures have
      become an indispensable tool for implant surgeons in managing residual ridges and
      the surrounding bone. Putty bone grafts have significantly superior handling
      characteristics in comparison to particulates. These include ease of placement,
      enhanced particle containment, and a viscous consistency that has allowed for
      unique delivery systems to be developed. The aim of this study was to report the
      clinical efficacy of calcium phosphosilicate (CPS) putty in a wide variety of
      indications related to implant reconstruction and to report the survival rate of
      implants placed in these grafted sites. The CPS putty was used as the graft
      material of choice. Treatments were categorized into following groups: extraction
      graft, extraction with immediate implant placement, all-on-four concept, peri
      implantitis treatment, bone augmentation before implant placement, implant
      replacement graft, and grafting around implant placed in resorbed ridges.
      Included in the analysis were 65 patients (36 men, 29 women) with a mean age of
      63 +/- 12 years. In total, 262 implants were placed. Four implants were diagnosed
      with peri-implantitis and were treated as described in category 4, for a total of
      266 grafted sites. Two implants from the extraction graft category and 3 implants
      from the all-on-four group were lost and replaced with successfully
      osseointegrated implants during a mean study follow-up period of 12.24 +/- 2.32
      months. The implant success rate at 1 year was 98.1% (257/262). Based on results
      of this large-scale, retrospective study we conclude that (1) the use of putty
      bone grafts can simplify bone-grafting procedures and reduce intraoperative time
      in various grafting indications, (2) this study verified the efficacy of a CPS
      putty bone graft biomaterial in a large array of implant-related surgical
      indications, and (3) implants placed in sites grafted with CPS putty yield very
      high survival rates. 

PMID- 25072733
TI  - Incidence of Cyp51 A key mutations in Aspergillus fumigatus-a study on primary
      clinical samples of immunocompromised patients in the period of 1995-2013.
AB  - As the incidence of azole resistance in Aspergillus fumigatus is rising and the
      diagnosis of invasive aspergillosis (IA) in immunocompromised patients is rarely
      based on positive culture yield, we screened our Aspergillus DNA sample
      collection for the occurrence of azole resistance mediating cyp51 A key
      mutations. Using two established, a modified and a novel polymerase chain
      reaction (PCR) assays followed by DNA sequence analysis to detect the most
      frequent mutations in the A. fumigatus cyp51 A gene conferring azole resistance
      (TR34 (tandem repeat), L98H and M220 alterations). We analyzed two itraconazole
      and voriconazole and two multi-azole resistant clinical isolates and screened 181
      DNA aliquots derived from clinical samples (blood, bronchoalveolar lavage (BAL),
      biopsies, cerebrospinal fluid (CSF)) of 155 immunocompromised patients of our
      Aspergillus DNA sample collection, previously tested positive for Aspergillus DNA
      and collected between 1995 and 2013. Using a novel PCR assay for the detection of
      the cyp51 A 46 bp tandem repeat (TR46) directly from clinical samples, we found
      the alteration in a TR46/Y121F/T289A positive clinical isolate. Fifty stored DNA
      aliquots from clinical samples were TR46 negative. DNA sequence analysis revealed
      a single L98H mutation in 2010, two times the L98H alteration combined with TR34
      in 2011 and 2012 and a so far unknown N90K mutation in 1998. In addition, four
      clinical isolates were tested positive for the TR34/L98H combination in the year
      2012. We consider our assay of epidemiological relevance to detect A. fumigatus
      azole resistance in culture-negative clinical samples of immunocompromised
      patients; a prospective study is ongoing. 

PMID- 25072735
TI  - The FDA's new advice on fish: it's complicated.
AB  - The Food and Drug Administration and Environmental Protection Agency recently
      issued an updated draft of advice on fish consumption for pregnant and
      breastfeeding women, after survey data indicated that the majority of pregnant
      women do not eat much fish and thus may have inadequate intake of the omega 3
      fatty acids eicosapentaenoic acid [EPA] and ducosahexaenoic acid [DHA]. Omega 3
      fatty acids are essential components of membranes in all cells of the body and
      are vitally important for normal development of the brain and retinal tissues
      (especially myelin and retinal photoreceptors) and for maintenance of normal
      neurotransmission and connectivity. They also serve as substrates for the
      synthesis of a variety of antiinflammatory and inflammation-resolving mediators,
      favorably alter the production of thromboxane and prostaglandin E2, and improve
      cardiovascular health by preventing fatal arrhythmias and reducing triglyceride
      and C-reactive protein levels. Maternal ingestion of adequate quantities of fish
      (defined in many studies as at least 340 g of oily fish each week) has been
      associated with better childhood IQ scores, fine motor coordination, and
      communication and social skills, along with other benefits. Although the FDA did
      not clarify which fish to eat, it specifically advised against eating fish with
      the highest mercury levels and implied that fish with high levels of EPA and DHA
      and low levels of mercury are ideal. The FDA draft did not recommend taking omega
      3 fatty acid or fish oil supplements instead of eating fish, which is advice that
      may reflect the fact that randomized controlled trials of DHA and EPA or fish oil
      supplementation generally have been disappointing and that the ideal daily dose
      of DHA and EPA is unknown. It seems safe to conclude that pregnant and nursing
      women should be advised to eat fish to benefit from naturally occurring omega 3
      fatty acids, to avoid fish with high levels of mercury and other contaminants,
      and, if possible, to choose fish with high levels of EPA and DHA. 

PMID- 25072737
TI  - Power morcellators: a review of current practice and assessment of risk.
AB  - Power morcellation has come under scrutiny because of a highly publicized case of
      disseminated leiomyosarcoma following a laparoscopic hysterectomy. A recent
      Federal and Drug Administration safety communication discouraging use of power
      morcellators on presumed uterine leiomyoma further highlights the need for
      reexamination of uterine tissue extraction. This clinical opinion aims to
      summarize current approaches to uterine/fibroid tissue extraction including the
      associated immediate and long-term potential risks of open power morcellation.
      The known data about risk of uterine sarcoma is reviewed followed by a discussion
      of acceptable risk and informed consent in the context of shared-decision making.

PMID- 25072738
TI  - Quality of life and associated socio-clinical factors after encephalitis in
      children and adults in England: a population-based, prospective cohort study.
AB  - OBJECTIVE: We sought to measure HRQoL in all-cause encephalitis survivors and
      assess the impact of various socio-clinical factors on outcome. METHODS: We used
      a prospective cohort study design, using the short-form 36 (SF-36) to measure the
      HRQoL in patients 15 years and older, and the short-form 10 (SF-10) for patients
      less than 15 years old. We posted questionnaires to individuals six months after
      discharge from hospital. All scores were normalised to the age- and sex-matched
      general population. We used multivariate statistical analysis to assess the
      relative association of clinical and socio-demographic variables on HRQoL in
      adults. RESULTS: Of 109 individuals followed-up, we received 61 SF-36 and twenty
      SF-10 questionnaires (response rate 74%). Patients scored consistently worse than
      the general population in all domains of the SF-36 and SF-10, although there was
      variation in individual scores. Infectious encephalitis was associated with the
      worst HRQoL in those aged 15 years and over, scoring on average 5.64 points less
      than immune-mediated encephalitis (95% CI -8.77- -2.89). In those aged less than
      15 years the worst quality of life followed encephalitis of unknown cause. Immuno
      compromise, unemployment, and the 35-44 age group all had an independent negative
      association with HRQoL. A poor Glasgow Outcome Score was most strongly associated
      with a poor HRQoL. Less than half of those who had made a 'good' recovery on the
      score reported a HRQoL equivalent to the general population. CONCLUSIONS:
      Encephalitis has adverse effects on the majority of survivors' wellbeing and
      quality of life. Many of these adverse consequences could be minimised by prompt
      identification and treatment, and with better rehabilitation and support for
      survivors.

PMID- 25072739
TI  - Collaborative brain-computer interface for aiding decision-making.
AB  - We look at the possibility of integrating the percepts from multiple non
      communicating observers as a means of achieving better joint perception and
      better group decisions. Our approach involves the combination of a brain-computer
      interface with human behavioural responses. To test ideas in controlled
      conditions, we asked observers to perform a simple matching task involving the
      rapid sequential presentation of pairs of visual patterns and the subsequent
      decision as whether the two patterns in a pair were the same or different. We
      recorded the response times of observers as well as a neural feature which
      predicts incorrect decisions and, thus, indirectly indicates the confidence of
      the decisions made by the observers. We then built a composite neuro-behavioural
      feature which optimally combines the two measures. For group decisions, we uses a
      majority rule and three rules which weigh the decisions of each observer based on
      response times and our neural and neuro-behavioural features. Results indicate
      that the integration of behavioural responses and neural features can
      significantly improve accuracy when compared with the majority rule. An analysis
      of event-related potentials indicates that substantial differences are present in
      the proximity of the response for correct and incorrect trials, further
      corroborating the idea of using hybrids of brain-computer interfaces and
      traditional strategies for improving decision making. 

PMID- 25072740
TI  - Aqueous self-assembly within the homologous peptide series AnK.
AB  - We compare the aqueous self-assembly behavior within the homologous peptide
      series AnK, where A is alanine, K is lysine, and n = 4, 6, 8, and 10. The aqueous
      peptide solubility, phi(s) (volume fraction), depends strongly on the number of
      hydrophobic alanine residues and decreases approximately as phi(s) ~ 10(-n). Also
      the self-assembly structure depends on n. A4K is highly water-soluble and shows
      no relevant self-assembly. A6K, which has been extensively studied previously,
      forms hollow nanotubes in water. A8K and A10K self-assembly is characterized here
      using a combination of small- and wide-angle X-ray scattering, static and dynamic
      light scattering, cryo transmission electron microscopy, and circular dichroism
      spectroscopy. They both form similar thin rodlike aggregates with lengths on the
      order of 100 nm and a biaxial cross-section with dimensions of 4 nm * 8 nm. We
      show that different sample preparation protocols result in different lengths of
      the A10K rodlike aggregates. On the basis of these findings, the question of
      thermodynamic equilibrium of peptide self-assembly is discussed.

PMID- 25072736
TI  - Prediction of preterm birth in twin gestations using biophysical and biochemical
      tests.
AB  - The objective of this study was to determine the performance of biophysical and
      biochemical tests for the prediction of preterm birth in both asymptomatic and
      symptomatic women with twin gestations. We identified a total of 19 tests
      proposed to predict preterm birth, mainly in asymptomatic women. In these women,
      a single measurement of cervical length with transvaginal ultrasound before 25
      weeks of gestation appears to be a good test to predict preterm birth. Its
      clinical potential is enhanced by the evidence that vaginal progesterone
      administration in asymptomatic women with twin gestations and a short cervix
      reduces neonatal morbidity and mortality associated with spontaneous preterm
      delivery. Other tests proposed for the early identification of asymptomatic women
      at increased risk of preterm birth showed minimal to moderate predictive
      accuracy. None of the tests evaluated in this review meet the criteria to be
      considered clinically useful to predict preterm birth among patients with an
      episode of preterm labor. However, a negative cervicovaginal fetal fibronectin
      test could be useful in identifying women who are not at risk for delivering
      within the next week, which could avoid unnecessary hospitalization and
      treatment. This review underscores the need to develop accurate tests for
      predicting preterm birth in twin gestations. Moreover, the use of interventions
      in these patients based on test results should be associated with the improvement
      of perinatal outcomes. 

PMID- 25072741
TI  - Molecular structure investigation of neutral, dimer and anion forms of 3,4
      pyridinedicarboxylic acid: a combined experimental and theoretical study.
AB  - In this study, the structural and vibrational analysis of 3,4
      pyridinedicarboxylic acid (3,4-PDCA) are presented using experimental techniques
      as FT-IR, FT-Raman, NMR, UV and quantum chemical calculations. FT-IR and FT-Raman
      spectra of 3,4-pyridinedicarboxylic acid in the solid phase are recorded in the
      region 4000-400 cm(-1) and 4000-50 cm(-1), respectively. The geometrical
      parameters and energies of all different and possible monomer, dimer, anion(-1)
      and anion(-2) conformers of 3,4-PDCA are obtained from Density Functional Theory
      (DFT) with B3LYP/6-311++G(d,p) basis set. There are sixteen conformers (C1C16)
      for this molecule (neutral form). The most stable conformer of 3,4-PDCA is the C1
      conformer. The complete assignments are performed on the basis of the total
      energy distribution (TED) of the vibrational modes calculated with scaled quantum
      mechanics (SQM) method. (1)H and (13)C NMR spectra are recorded and the chemical
      shifts are calculated by using DFT/B3LYP methods with 6-311++G(d,p) basis set.
      The UV absorption spectrum of the studied compound is recorded in the range of
      200-400 nm by dissolved in ethanol. The optimized geometric parameters were
      compared with experimental data via the X-ray results derived from complexes of
      this molecule. In addition these, molecular electrostatic potential (MEP),
      thermodynamic and electronic properties, HOMO-LUMO energies and Mulliken atomic
      charges, are performed.

PMID- 25072742
TI  - Cross-dehydrocoupling: a novel synthetic route to P-B-P-B chains.
AB  - Transition-metal-catalyzed dehydrocoupling of tert-butylferrocenylphosphine
      borane (2) with [{Rh(MU-Cl)(1,5-cod)}2] (cod = cyclooctadiene) as the catalyst
      gave the homocoupled product [Fc(tBu)(H)P(BH2)P(Fc)(tBu)(BH2X)] [3; Fc =
      Fe(C5H5)(C5H4), X = H/Cl], while cross-dehydrocoupling with the tertiary
      phosphine-boranes P(tBu)(nBu)2(BH3) (2a) and PPh(nBu)2(BH3) (2b) using [Rh(1,5
      cod)2]OTf (OTf = trifluoromethanesulfonate) gave the first cross-dehydrocoupled
      products reported to date, [Fc(tBu)(BH3)P(BH2)P(tBu)(nBu)2] (4) and
      [Fc(tBu)(BH3)P(BH2)PPh(nBu)2] (5), in moderate yields. Compounds 2-5 were
      characterized by NMR spectroscopy ((1)H, (13)C, (31)P, and (11)B), IR
      spectroscopy, mass spectrometry, and single-crystal X-ray structure
      determination. 

PMID- 25072743
TI  - Functional and metabolic disorders in celiac disease: new implications for
      nutritional treatment.
AB  - Celiac disease (CD) is a chronic disease causing the inflammation of the proximal
      small intestine, in genetically predisposed individuals. This is triggered by the
      consumption of the gluten protein and the side effects of the disease are
      mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant
      consequence of CD is malnutrition due to malabsorption (with diarrhea, weight
      loss, nutritional deficiencies, and altered blood parameters), especially in
      patients who do not show strict adherence to GFD treatment. Recent evidence shows
      that, despite a lifelong GFD, some functional disorders persist, such as
      compromised gallbladder function and motility, exocrine pancreatic insufficiency,
      increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty
      liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities
      may predispose to the occurrence of overweight and obesity even in CD patients.
      This review focuses on the principal functional and metabolic disorders in both
      treated and untreated CD, ranging from alterations of the gastrointestinal system
      to impaired glucose and lipid metabolism and insulin secretion with the aim of
      providing new implications beyond a GFD, for an ad hoc nutrition treatment in
      these patients.

PMID- 25072745
TI  - Is professionalism fractal-like?

PMID- 25072747
TI  - Uptake enhancement of curcumin encapsulated into phosphatidylcholine-shielding
      micelles by cancer cells.
AB  - Internalization of drugs by cancer cells is a crucial factor to impact cancer
      treatment effect. Curcumin, having inhibitory effect on a variety of cancers, was
      encapsulated into micelles of six-arm star-shape poly(epsilon-caprolactone)-b
      poly(2-methacryloyloxyethylphosphorylcholine) (6sPCL-PMPC) in order to enhance
      its concentration in blood and cellular uptake. Micelles and curcumin-loaded
      micelles were prepared by the solvent-evaporation method. Drug-loading content
      and drug-loading efficiency could be achieved as high as 18.9 and 98%. MTT
      results showed that these curcumin-loaded micelles displayed significant cell
      cytotoxicity, while these blank micelles were noncytotoxic. The curcumin-loaded
      6sPCL-PMPC micelles showed higher efficiency to kill HeLa cells than that of
      curcumin-loaded PCL-PEG micelles. The cellular uptake study indicated that the
      curcumin encapsulated into 6sPCL-PMPC micelles was ingested more by HeLa cells
      than the curcumin encapsulated into PCL-PEG micelles. In conclusion, the micelles
      with phosphatidylcholine (PC) groups as their exterior can greatly enhance the
      uptake by HeLa cells and the cytotoxicity of curcumin due to excellent
      internalization by cancer cells. 

PMID- 25072748
TI  - Reactivity of organothorium complexes with TEMPO.
AB  - Reactions of the 2,2,6,6-tetramethylpiperidin-1-oxyl radical (TEMPO) with thorium
      metallocenes have been examined to investigate both the radical reaction patterns
      for organothorium complexes and the coordination chemistry of TEMPO with thorium.
      (eta(5)-C5Me5)2ThMe2 reacts with 2 equiv of TEMPO to generate 1-methoxy-2,2,6,6
      tetramethylpiperidine (Me-TEMPO) and (eta(5)-C5Me5)2ThMe(eta(1)-TEMPO), which
      contains a TEMPO(-) anion coordinated to thorium through oxygen only. (eta(5)
      C5Me5)2Th(eta(1)-C3H5)(eta(3)-C3H5), synthesized from (eta(5)-C5Me5)2ThBr2 and
      (C3H5)MgBr, reacts with 2 equiv of TEMPO to form 1-(2-propen-1-yloxy)-2,2,6,6
      tetramethylpiperidine (allyl-TEMPO) and (eta(5)-C5Me5)2Th(eta(1)-C3H5)(eta(1)
      TEMPO). Although bis(TEMPO) metallocenes were not obtained in these reactions,
      the methyl group in (eta(5)-C5Me5)2ThMe(eta(1)-TEMPO) is reactive with 1 equiv of
      CuBr to form (eta(5)-C5Me5)2ThBr(eta(1)-TEMPO). The bis(TEMPO) metallocene
      (eta(5)-C5Me5)2Th(eta(1)-TEMPO)2 is accessible in the reaction of [(eta(5)
      C5Me5)2ThH2]2 with 4 equiv of TEMPO. In contrast, (eta(5)-C5Me5)2ThBr2 reacts
      with 2 equiv of TEMPO by loss of C5Me5 to form (C5Me5)2 and (eta(2)-TEMPO)2ThBr2,
      in which the TEMPO(-) anions bind through oxygen and nitrogen. The bromide ions
      in (eta(2)-TEMPO)2ThBr2 can be replaced by an additional 2 equiv of TEMPO in the
      presence of 2 equiv of KC8 to form the per(TEMPO) complex Th(eta(1)
      TEMPO)2(eta(2)-TEMPO)2. ThBr4(THF)4 reacts with TEMPO to form ThBr4(THF)2(eta(1)
      TEMPO), which contains an oxygen-bound TEMPO radical. The Th(3+) complex (eta(5)
      C5Me4H)3Th is oxidized in the presence of TEMPO, without ligand loss, to afford
      the Th(4+) species (eta(5)-C5Me4H)3Th(eta(1)-TEMPO). The reactions show that
      TEMPO can react with organothorium complexes in several ways including
      coordination, anion substitution, and cyclopentadienyl replacement. 

PMID- 25072750
TI  - Medical school accreditation in China: a Sino-Australian collaboration.
AB  - In 2008, China established a medical school accreditation process based on
      international standards and guidelines. Twenty schools had been accredited by
      2013 and it is intended to accredit all 137 schools by 2020. To achieve this
      ambitious aim, Chinese medical educators have entered into collaboration with
      their Australian counterparts, engendered by mutual membership of the Association
      for Medical Education in the Western Pacific Region, a regional division of the
      World Federation for Medical Education. The collaboration began in 2000 as
      informal discussions at regional meetings and has since developed three major
      components: workshops held throughout China for potential assessors and for
      medical schools undergoing accreditation; visits by Chinese accreditors to
      Australia to observe Australian Medical Council processes; and participation by
      Australian assessors in the accreditation of Chinese medical schools. The
      incremental steps that led to this unique bi-national venture are outlined in the
      context of other international developments in accreditation of medical
      education. Then, the preparation, piloting and implementation of accreditation
      standards and guidelines with Chinese specifications are described. Finally, the
      outcomes achieved thus far and the challenges remaining are discussed.

PMID- 25072749
TI  - Superior in vitro stimulation of human CD8+ T-cells by whole virus versus split
      virus influenza vaccines.
AB  - Pandemic and seasonal influenza viruses cause considerable morbidity and
      mortality in the general human population. Protection from severe disease may
      result from vaccines that activate antigen-presenting DC for effective
      stimulation of influenza-specific memory T cells. Special attention is paid to
      vaccine-induced CD8+ T-cell responses, because they are mainly directed against
      conserved internal influenza proteins thereby presumably mediating cross
      protection against circulating seasonal as well as emerging pandemic virus
      strains. Our study showed that influenza whole virus vaccines of major seasonal A
      and B strains activated DC more efficiently than those of pandemic swine-origin
      H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus
      vaccines had a low ability to activate DC, regardless which strain was
      investigated. We also observed that whole virus vaccines stimulated virus
      specific CD8+ memory T cells much stronger compared to split virus counterparts,
      whereas both vaccine formats activated CD4+ Th cell responses similarly.
      Moreover, our data showed that whole virus vaccine material is delivered into the
      cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells.
      We conclude that vaccines against seasonal and pandemic (-like) influenza strains
      that aim to stimulate cross-reacting CD8+ T cells should include whole virus
      rather than split virus formulations. 

PMID- 25072751
TI  - Protease Nexin-1 affects the migration and invasion of C6 glioma cells through
      the regulation of urokinase Plasminogen Activator and Matrix Metalloproteinase
      9/2.
AB  - Protease Nexin-1 (PN-1) or Serpine2 is a physiological regulator of extracellular
      proteases as thrombin and urokinase (uPA) in the brain. Besides, PN-1 is also
      implicated in some human cancers and further identified as a substrate for Matrix
      Metalloproteinase (MMP)-9, a key enzyme in tumor invasiveness. Our aim was to
      study the role of PN-1 in the migration and invasive potential of glioma cells,
      using the rat C6 glioma cell line as stable clones transfected with pAVU6+27
      vector expressing PN-1 short-hairpin RNA. We find that PN-1 knockdown enhanced
      the in vitro migration and invasiveness of C6 cells which also showed a strong
      gelatinolytic activity by in situ zymography. PN-1 silencing did not alter
      prothrombin whereas increased uPA, MMP-9 and MMP-2 expression levels and
      gelatinolytic activity in a conditioned medium from stable C6 cells. Selective
      inhibitors for MMP-9 (Inhibitor I), MMP-2 (Inhibitor III) or exogenous
      recombinant PN-1 added to the culture medium of C6 silenced cells restored either
      the migration and invasive ability or gelatinolytic activity thus validating the
      specificity of PN-1 silencing strategy. Phosphorylation levels of extracellular
      signal-related kinases (Erk1/2 and p38 MAPK) involved in MMP-9 and MMP-2
      signaling were increased in PN-1 silenced cells. This study shows that PN-1
      affects glioma cell migration and invasiveness through the regulation of uPA and
      MMP-9/2 expression levels which contribute to the degradation of extracellular
      matrix during tumor invasion. 

PMID- 25072752
TI  - Poly (ADP-ribose) polymerase inhibition synergizes with the NF-kappaB inhibitor
      DHMEQ to kill hepatocellular carcinoma cells.
AB  - Poly (ADP-ribose) polymerase (PARP) enzymes play a key role in the cellular
      machinery responsible for DNA repair. Dehydroxymethylepoxyquinomicin (DHMEQ), a
      new inhibitor of NF-kappaB, induces oxidative stress and DNA damage. The effects
      of DHMEQ in combination with Olaparib (PARP inhibitor) were studied on
      hepatocellular carcinoma (HCC) cells. The DHMEQ-Olaparib combination
      synergistically inhibited cell viability, cell proliferation and colony formation
      of Hep3B, but had additive effects on Huh7 cells. The synergistic effects of the
      combination correlated with increased apoptosis, caspase 3/7 activity and PARP
      cleavage. There was an induction of an endoplasmic reticulum (ER) stress response
      with significant up-regulation of CHOP and TRB3 genes and splicing of XBP1 mRNA
      in Hep3B cells but not in Huh7 cells. Silencing of the TRB3 mRNA in Hep3B cells
      reversed the reduction in viability caused by DHMEQ-Olaparib treatment, while
      depletion of unspliced XBP1 mRNA in DHMEQ-Olaparib-treated Huh7 cells reduced
      viability. ROS production was increased after DHMEQ-Olaparib treatment of Hep3B,
      which caused DNA damage by an accumulation of gammaH2AX, increased AKT
      phosphorylation and reduced cell viability. The combination reduced Rad51 nuclear
      foci in Hep3B cells (not Huh7 cells), and silencing of Rad51 enhanced sensitivity
      of Huh7 cells to the DHMEQ-Olaparib combination. Knockdown of AKT in Hep3B cells
      restored the number of Rad51 nuclear foci after DHMEQ-Olaparib treatment. In
      summary, the DHMEQ-Olaparib combination induced ROS production, which killed HCC
      cells via DNA damage that could not be repaired by Rad51. SUMMARY: PARPs and NF
      kappaB are frequently deregulated in HCC. The DHMEQ-Olaparib combination exerted
      synergistic anti-tumour effects on HCC cells through ROS production via DNA
      damage that could not be repaired by Rad51. This suggested that the DHMEQ
      Olaparib combination could be used to treat tumours that were resistant to
      Olaparib treatment.

PMID- 25072753
TI  - Extent, risk factors, and outcome of fluid overload after pediatric heart
      surgery*.
AB  - OBJECTIVES: Fluid overload is associated with poor PICU outcomes in different
      populations. Little is known about fluid overload in children undergoing cardiac
      surgery. We described fluid overload after cardiac surgery, identified risk
      factors of worse fluid overload and also determined if fluid overload predicts
      longer length of PICU stay, prolonged mechanical ventilation (length of
      ventilation) and worse lung function as estimated by the oxygenation index.
      DESIGN: Retrospective cohort study. SETTING: Montreal Children's Hospital PICU,
      Montreal, Canada. PATIENTS: Patients 18 years or younger undergoing cardiac
      surgery (2005-2007). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Cumulative fluid overload % was calculated as [(total fluid in - out in
      L)/admission weight (kg) * 100] and expressed as PICU peak cumulative fluid
      overload % throughout admission and PICU day 2 cumulative fluid overload %.
      Primary outcomes were length of stay and length of ventilation. The secondary
      outcome was oxygenation index. Fluid overload risk factors were evaluated using
      stepwise linear regression. Fluid overload-outcome relations were evaluated using
      stepwise Cox regression (length of stay, length of ventilation) and generalized
      estimating equations (daily PICU cumulative fluid overload % and oxygenation
      index repeated measures). There were 193 eligible surgeries. Peak cumulative
      fluid overload % was 7.4% +/- 11.2%. Fluid overload peaked on PICU day 2. Lack of
      past cardiac surgery (p = 0.04), cyanotic heart disease (p = 0.03), and early
      postoperative fluids (p = 0.0001) was independently associated with higher day 2
      fluid overload %. Day 2 fluid overload % predicted longer length of stay
      (adjusted hazard ratio, 0.95; 95% CI, 0.92-0.99; p = 0.009) and length of
      ventilation (adjusted hazard ratio, 0.97; 95% CI, 0.94-0.99; p = 0.03). In
      patients without cyanotic heart disease, worse daily fluid overload % predicted
      worse daily oxygenation index. CONCLUSION: Fluid overload occurs early after
      cardiac surgery and is associated with prolonged PICU length of stay and
      ventilation. Future fluid overload avoidance trials may confirm or refute a true
      fluid overload-outcome causative association.

PMID- 25072754
TI  - Development and validation of a quality-of-life questionnaire for mechanically
      ventilated ICU patients.
AB  - OBJECTIVE: To develop and validate a new instrument for measuring health-related
      quality of life in mechanically ventilated patients in the ICU. DESIGN: Expert
      panel consensus and a prospective longitudinal survey. SETTING: Urban, academic,
      tertiary care medical center. PATIENTS: One hundred fifteen awake, mechanically
      ventilated, ICU patients who either received a tracheostomy or remained
      endotracheally intubated. INTERVENTIONS: A new quality-of-life instrument was
      developed and validated by using pilot study data; informal interviews of
      patients, families, and nurses; expert panel consensus; and item analyses. The
      new instrument was used to measure quality of life at three time points (5 d, 10
      d, and 15 d after intubation). MEASUREMENTS AND MAIN RESULTS: A new 12-item
      quality-of-life questionnaire for mechanically ventilated patients was developed.
      Patients' responses to the quality-of-life questionnaire revealed moderate-to
      high correlations with EuroQol scores (r = -0.4 to -0.9) and the EuroQol Visual
      Analog Scale (r = 0.6-0.9) across the three times and a moderate correlation with
      the Sequential Organ Failure Assessment tool (r = 0.5) at 10 days after
      intubation. Cronbach alpha ranged from 0.80 to 0.94 across the three times. The
      quality-of-life questionnaire for mechanically ventilated patients was responsive
      to changes in treatment modalities (tracheostomy vs no tracheostomy and early vs
      late tracheostomy demarcated by 10 d of intubation). Exploratory factor analysis
      revealed that this instrument was unidimensional in nature. CONCLUSIONS: The new
      quality-of-life questionnaire for mechanically ventilated patients is valid and
      can reliably measure quality of life in mechanically ventilated ICU patients. It
      may provide clinicians with an accurate assessment of patients' quality of life
      and facilitate optimal decision making regarding patients' ICU plan of care.

PMID- 25072755
TI  - Power and limitations of daily prognostications of death in the medical ICU for
      outcomes in the following 6 months.
AB  - OBJECTIVES: We tested the power of clinicians' predictions that a medical ICU
      patient would "die before hospital discharge" for both survival to discharge and
      for outcomes at 6 months. DESIGN: We restricted our analyses to patients who had
      been in the medical ICU at least 72 hours and for whom we had follow-up at 6
      months after medical ICU admission. For 350 medical ICU patients, on each medical
      ICU day, we asked their attending physician, fellow, resident, and primary nurse
      one question-"do you think this patient will die in hospital or survive to be
      discharged"? We correlated these responses with 6-month outcomes (death and/or
      Barthel score for survivors). RESULTS: We obtained over 6,000 predictions on
      2,271 medical ICU patient-days. Of 350 medical ICU patients who stayed more than
      72 hours, 143 patients (41%) had discordant predictions-that is, on the same
      medical ICU day, at least one provider predicted survival, whereas another
      predicted death before discharge. As we have shown previously, predictions of
      "death before discharge" were imperfect-only 104 of 187 of patients with a
      prediction of death (56%) actually died in hospital. However, this is the central
      finding of our study, and predictions of death before discharge were much more
      accurate for 6-month outcomes. Of 120 patients with a corroborated prediction of
      death before discharge (93%), 112 patients had died within 6 months of medical
      ICU discharge, and only 4% were functioning with a Barthel score more than 70. In
      contrast, 67 of 163 patients who did not have any prediction of death before
      discharge (41%) were alive with Barthel score more than 70 at 6 months.
      CONCLUSIONS: Fewer than 4% of medical ICU patients who required 72 hours of
      medical ICU care and had a corroborated prediction of death before discharge were
      alive at 6 months and functioning with a Barthel score more than 70.

PMID- 25072756
TI  - Burst suppression on processed electroencephalography as a predictor of postcoma
      delirium in mechanically ventilated ICU patients.
AB  - OBJECTIVES: Many patients, due to a combination of illness and sedatives, spend a
      considerable amount of time in a comatose state that can include time in burst
      suppression. We sought to determine if burst suppression measured by processed
      electroencephalography during coma in sedative-exposed patients is a predictor of
      post-coma delirium during critical illness. DESIGN: Observational convenience
      sample cohort. SETTING: Medical and surgical ICUs in a tertiary care medical
      center. PATIENTS: Cohort of 124 mechanically ventilated ICU patients.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Depth of sedation was
      monitored twice daily using the Richmond Agitation-Sedation Scale and
      continuously monitored by processed electroencephalography. When noncomatose,
      patients were assessed for delirium twice daily using Confusion Assessment Method
      for the ICU. Multiple logistic regression and Cox proportional hazards regression
      were used to assess associations between time in burst suppression and both
      prevalence and time to resolution of delirium, respectively, adjusting for time
      in deep sedation and a principal component score consisting of Acute Physiology
      and Chronic Health Evaluation II score and cumulative doses of sedatives while
      comatose. Of the 124 patients enrolled and monitored, 55 patients either never
      had coma or never emerged from coma, yielding 69 patients for whom we performed
      these analyses; 42 of these 69 (61%) had post-coma delirium. Most patients had
      burst suppression during coma, although often short-lived (median [interquartile
      range] time in burst suppression, 6.4 [1-58] min). After adjusting for
      covariates, even this short time in burst suppression independently predicted a
      higher prevalence of post-coma delirium (odds ratio, 4.16; 95% CI, 1.27-13.62; p
      = 0.02) and a lower likelihood (delayed) resolution of delirium (hazard ratio,
      0.78; 95% CI, 0.53-0.98; p = 0.04). CONCLUSIONS: Time in burst suppression during
      coma, as measured by processed electroencephalography, was an independent
      predictor of prevalence and time to resolution of postcoma/post-deep sedation
      delirium. These findings of this single-center investigation support lighter
      sedation strategies.

PMID- 25072757
TI  - Simplified severe sepsis protocol: a randomized controlled trial of modified
      early goal-directed therapy in Zambia.
AB  - OBJECTIVE: To assess the efficacy of a simple, goal-directed sepsis treatment
      protocol for reducing mortality in patients with severe sepsis in Zambia. DESIGN:
      Single-center nonblinded randomized controlled trial. SETTING: Emergency
      department, ICU, and medical wards of the national referral hospital in Lusaka,
      Zambia. PATIENTS: One hundred twelve patients enrolled within 24 hours of
      admission with severe sepsis, defined as systemic inflammatory response syndrome
      with suspected infection and organ dysfunction INTERVENTIONS: : Simplified Severe
      Sepsis Protocol consisting of up to 4 L of IV fluids within 6 hours, guided by
      jugular venous pressure assessment, and dopamine and/or blood transfusion in
      selected patients. Control group was managed as usual care. Blood cultures were
      collected and early antibiotics administered for both arms. MEASUREMENTS AND MAIN
      RESULTS: Primary outcome was in-hospital all-cause mortality. One hundred nine
      patients were included in the final analysis and 88 patients (80.7%) were HIV
      positive. Pulmonary infections were the most common source of sepsis. In-hospital
      mortality rate was 64.2% in the intervention group and 60.7% in the control group
      (relative risk, 1.05; 95% CI, 0.79-1.41). Mycobacterium tuberculosis complex was
      isolated from 31 of 82 HIV-positive patients (37.8%) with available mycobacterial
      blood culture results. Patients in Simplified Severe Sepsis Protocol received
      significantly more IV fluids in the first 6 hours (2.7 L vs 1.7 L, p = 0.002).
      The study was stopped early because of high mortality rate among patients with
      hypoxemic respiratory failure in the intervention arm (8/8, 100%) compared with
      the control arm (7/10, 70%; relative risk, 1.43; 95% CI, 0.95-2.14). CONCLUSION:
      Factors other than tissue hypoperfusion probably account for much of the end
      organ dysfunction in African patients with severe sepsis. Studies of fluid-based
      interventions should utilize inclusion criteria to accurately capture patients
      with hypovolemia and tissue hypoperfusion who are most likely to benefit from
      fluids. Exclusion of patients with severe respiratory distress should be
      considered when ventilatory support is not readily available.

PMID- 25072758
TI  - Low-dose corticosteroid treatment in septic shock: a propensity-matching study.
AB  - OBJECTIVE: Given conflicting data and current guidelines, low-dose
      corticosteroids are often used in the treatment of septic shock. To evaluate the
      therapeutic benefit of early low-dose corticosteroid in patients with septic
      shock. DESIGN: Retrospective, multicenter, propensity-matched cohort study.
      SETTING: ICUs of 28 academic and community hospitals in three countries between
      1996 and 2007. SUBJECTS: Six thousand six hundred sixty-three eligible patients
      with septic shock of whom 1,838 received IV low-dose corticosteroid treatment
      within 48 hours of the diagnosis of septic shock and were matched to a comparable
      group who did not receive low-dose corticosteroid. MEASUREMENTS AND MAIN RESULTS:
      The primary outcome was 30-day mortality. Mortality analyses were stratified by
      severity of illness (Acute Physiology and Chronic Health Evaluation II quartile).
      Using a Cox proportional hazards model, corticosteroid therapy was associated
      with similar 30-day mortality when compared with the matched control cohort
      (652/1,838 [35.5%] vs 641/1,838 [34.9%]; hazard ratio, 0.98; 95% CI, 0.88-1.10; p
      = 0.77). In the subgroup of patients with the Acute Physiology and Chronic Health
      Evaluation II score quartile more than or equal to 30, low-dose corticosteroid
      was associated with lower mortality (232/461 [50.6%] vs 251/450 [55.8%]; hazard
      ratio, 0.81; 95% CI, 0.68-0.97; p = 0.02). In logistic regression models,
      corticosteroid therapy was not associated with reductions in ICU (556/1,838
      [30.3%] vs 558/1,838 [30.4%]; odds ratio, 0.99; 95% CI, 0.86-1.15; p = 0.94) or
      hospital mortality (797/1,838 [43.4%] vs 773/1,838 [42.1%]; odds ratio, 1.05; 95%
      CI, 0.93-1.20; p = 0.42). Similarly, there were no significant differences in
      ventilator- (median and interquartile range, 13 [0-25] vs 15 [0-25]; p = 0.8) and
      pressor/inotrope-free days (median and interquartile range, 25 [3-27] vs 24 [2
      28]; p = 0.63) up to 30 days between groups. CONCLUSION: Early administration of
      low-dose corticosteroid is not associated with decreased mortality when it is
      administered to unselected patients with septic shock. A beneficial effect of low
      dose corticosteroid on mortality may exist in patients with the highest severity
      of illness. Future trials of low-dose corticosteroid in septic shock should
      consider restricting the study population to this cohort.

PMID- 25072759
TI  - Cerebral performance category at hospital discharge predicts long-term survival
      of cardiac arrest survivors receiving targeted temperature management*.
AB  - OBJECTIVE: Despite recent advancements in post-cardiac arrest resuscitation, the
      optimal measurement of postarrest outcome remains unclear. We hypothesized that
      Cerebral Performance Category score can predict the long-term outcome of
      postarrest survivors who received targeted temperature management during their
      postarrest hospital care. DESIGN: Retrospective chart review. SETTING: Two
      academic medical centers from May 2005 to December 2012. PATIENTS: The medical
      records of 2,417 out-of-hospital and in-hospital patients post cardiac arrest
      were reviewed to identify 140 of 582 survivors who received targeted temperature
      management. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Cerebral
      Performance Category scores at hospital discharge were determined by three
      independent abstractors. The 1-month, 6-month, and 12-month survival of these
      patients was determined by reviewing hospital records and querying the Social
      Security Death Index and by follow-up telephone calls. The association of
      unadjusted long-term survival and adjusted survival with Cerebral Performance
      Category was calculated. Of the 2,417 patients who were identified to have
      undergone cardiac arrest, 24.1% (582/2,417) were successfully resuscitated, of
      whom 24.1% (140/582) received postarrest targeted temperature management.
      Overall, 42.9% of patients (60/140) were discharged with Cerebral Performance
      Category 1, 27.1% (38/140) with Cerebral Performance Category 2, 18.6% (26/140)
      with Cerebral Performance Category 3, and 11.4% (16/140) with Cerebral
      Performance Category 4. Cerebral Performance Category 1 survivors had the highest
      long-term survival followed by Cerebral Performance Categories 2 and 3, with
      Cerebral Performance Category 4 having the lowest long-term survival (p < 0.001,
      log-rank test). We found that Cerebral Performance Category 3 (hazard ratio =
      3.62, p < 0.05) and Cerebral Performance Category 4 (hazard ratio = 12.73, p <
      0.001) remained associated with worse survival after adjusting for age, gender,
      race, shockable rhythm, time to targeted temperature management initiation, total
      duration of resuscitation, withdrawal of care, and location of arrest.
      CONCLUSION: Patients with different Cerebral Performance Category scores at
      discharge have significantly different survival trajectories. Favorable Cerebral
      Performance Category at hospital discharge predicts better long-term outcomes of
      survivors of cardiac arrest who received targeted temperature management than
      those with less favorable Cerebral Performance Category scores.

PMID- 25072760
TI  - Recombinant human erythropoietin pretreatment attenuates acute renal tubular
      injury against ischemia-reperfusion by restoring transient receptor potential
      channel-6 expression and function in collecting ducts.
AB  - OBJECTIVE: Acute renal tubular injury is a serious complication in the
      postoperative period, which is associated with high mortality and increased ICU
      stay. We aimed to demonstrate the protective effect of rhEPO against acute
      tubular injury induced by ischemia-reperfusion and to explore the mechanism of
      canonical transient receptor potential channel-6. DESIGN: Randomized laboratory
      animal study. SETTINGS: Animal research laboratory. INTERVENTIONS: Male Sprague
      Dawley rats were randomly divided into three groups: the sham group, the control
      group, and the rhEPO group. Experimental acute tubular injury was established in
      rats by bilateral renal arterial occlusion for 30 minutes followed by
      reperfusion. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained for
      cystatin-C and neutrophil gelatinase-associated lipocalin measurements by enzyme
      linked immunosorbance assays. Seventy-two hours after reperfusion, urine samples
      were collected for osmolality and fractional excretion of sodium (%) assays on a
      chemistry analyzer. Kidneys were harvested at 24, 48, and 72 hours after
      reperfusion. Transient receptor potential channel-6, aquaporin-2, and Na,K-ATPase
      expression in collecting ducts were studied by immunofluorescence and Western
      blot. Coimmunoprecipitations were also performed to identify the possible
      signalplex relation between transient receptor potential channel-6 and aquaporin
      2 or Na,K-ATPase channels. RhEPO pretreatment significantly inhibited serum
      cystatin-C (2 hr: 453 +/- 64 MUg/L vs 337 +/- 28 MUg/L, p < 0.01), serum
      neutrophil gelatinase-associated lipocalin (72 hr: 1,175 +/- 107 ng/L vs 1,737 +/
      402 ng/L, p < 0.05), and urinary fractional excretion of sodium (%) increase
      (0.9 +/- 0.1 vs 2.2 +/- 0.8, p < 0.05) and alleviated the decrease of urinary
      osmolality (1,293 +/- 101 mosmol/kg H2O vs 767 +/- 91 mosmol/kg H2O, p < 0.05)
      induced by ischemia-reperfusion injury. Meanwhile, recombinant human
      erythropoietin greatly improved the ischemia-reperfusion-induced attenuation of
      transient receptor potential channel-6 expression (48 hr: 42% +/- 2% vs 67% +/-
      2% and 72 hr: 55% +/- 2% vs 66% +/- 2%), as well as aquaporin-2 and Na,K-ATPase
      expression in collecting ducts. Transient receptor potential channel-6
      functionally interacted with Na,K-ATPase but not aquaporin-2. CONCLUSIONS:
      Recombinant human erythropoietin pretreatment at the dose of 5,000 IU/kg potently
      prevented ischemia-reperfusion-induced acute tubular injury, which might be
      partly attributed to the restoring the effect of transient receptor potential
      channel-6 expression and collecting duct function.

PMID- 25072762
TI  - Bradycardia during therapeutic hypothermia is associated with good neurologic
      outcome in comatose survivors of out-of-hospital cardiac arrest.
AB  - OBJECTIVE: Comatose patients resuscitated after out-of-hospital cardiac arrest
      receive therapeutic hypothermia. Bradycardia is frequent during therapeutic
      hypothermia, but its impact on outcome remains unclear. We explore a possible
      association between bradycardia during therapeutic hypothermia and neurologic
      outcome in comatose survivors of out-of-hospital cardiac arrest. DESIGN:
      Retrospective cohort study, from January 2009 to January 2011. SETTING:
      University hospital medical and cardiac ICUs. PATIENTS: One hundred eleven
      consecutive comatose out-of-hospital cardiac arrest patients treated with
      therapeutic hypothermia. INTERVENTIONS: Patients treated with standardized
      treatment protocol after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: All out
      of-hospital cardiac arrest patients' records were reviewed. Hemodynamic data were
      obtained every fourth hour during the first days. The patients were in
      temperature target range (32-34 degrees C) 8 hours after out-of-hospital cardiac
      arrest and dichotomized into bradycardia and nonbradycardia groups depending on
      their actual heart rate less than or equal to 60 beats/min or more than 60
      beats/min at that time. Primary endpoint was Cerebral Performance Category score
      at hospital discharge. More nonbradycardia group patients received epinephrine
      during resuscitation and epinephrine and norepinephrine in the early in-hospital
      period. They also had lower base excess at admission. Survival rate with
      favorable outcome was significantly higher in the bradycardia than the
      nonbradycardia group (60% vs 37%, respectively, p = 0.03). For further heart rate
      quantification, patients were divided into quartiles: less than or equal to 49
      beats/min, 50-63 beats/min, 64-77 beats/min, and more than or equal to 78
      beats/min, with respective proportions of patients with good outcome at discharge
      of 18 of 27 (67%), 14 of 25 (56%), 12 of 28 (43%), and 7 of 27 (26%) (p = 0.002).
      Patients in the lowest quartile had significantly better outcome than the higher
      groups (p = 0.027), whereas patients in the highest quartile had significantly
      worse outcome than the lower three groups (p = 0.013). CONCLUSIONS: Bradycardia
      during therapeutic hypothermia was associated with good neurologic outcome at
      hospital discharge. Our data indicate that bradycardia should not be aggressively
      treated in this period if mean arterial pressure, lactate clearance, and diuresis
      are maintained at acceptable levels. Studies, both experimental and clinical, are
      warranted.

PMID- 25072761
TI  - Interaction between fluids and vasoactive agents on mortality in septic shock: a
      multicenter, observational study.
AB  - OBJECTIVE: Fluids and vasoactive agents are both used to treat septic shock, but
      little is known about how they interact or the optimal way to administer them. We
      sought to determine how hospital mortality was influenced by combined use of
      these two treatments. DESIGN: Retrospective evaluation using multivariable
      logistic regression to evaluate the association between hospital mortality and
      categorical variables representing initiation of vasoactive agents and volumes of
      IV fluids given 0-1, 1-6, and 6-24 hours after onset, including interactions and
      adjusting for potential confounders. SETTING: ICUs of 24 hospitals in 3
      countries. PATIENTS: Two thousand eight hundred forty-nine patients who survived
      more than 24 hours after after onset of septic shock, admitted between 1989 and
      2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fluids and vasoactive
      agents had strong, interacting associations with mortality (p < 0.0001).
      Mortality was lowest when vasoactive agents were begun 1-6 hours after onset,
      with more than 1 L of fluids in the initial hour after shock onset, more than 2.4
      L from hours 1-6, and 1.6-3.5 L from 6 to 24 hours. The lowest mortality rates
      were associated with starting vasoactive agents 1-6 hours after onset.
      CONCLUSIONS: The focus during the first hour of resuscitation for septic shock
      should be aggressive fluid administration, only thereafter starting vasoactive
      agents, while continuing aggressive fluid administration. Starting vasoactive
      agents in the initial hour may be detrimental, and not all of that association is
      due to less fluids being given with such early initiation of vasoactive agents.

PMID- 25072763
TI  - Cerebral oximetry assessed by near-infrared spectrometry during preeclampsia: an
      observational study: impact of magnesium sulfate administration.
AB  - OBJECTIVES: To determine the regional cerebral oxygen saturation of hemoglobin
      (rcSO2) in severe preeclamptic parturients exhibiting neurologic symptoms
      compared with healthy pregnant women (control) and to describe the effects of
      MgSO4 infusion on rcSO2 and cerebral and systemic hemodynamic variables. DESIGN:
      Prospective, observational study. SETTING: Obstetric critical care unit in a
      university-affiliated hospital. PATIENTS: Twenty severe preeclamptic parturients
      presenting with neurologic signs before any administration of MgSO4, and 20
      control parturients. INTERVENTION: Infusion of MgSO4 in severe preeclamptic
      patients. MEASUREMENTS AND MAIN RESULTS: We measured rcSO2 using near-infrared
      spectroscopy, blood flow velocities of the middle cerebral artery, and cardiac
      output at baseline, 5 minutes, 1 hour, and 6 hours after the MgSO4 bolus (4 g),
      followed by continuous MgSO4 infusion (1 g/h). These measurements were also
      obtained in 20 control parturients at baseline and 6 hours. Baseline rcSO2 was
      significantly lower in the severe preeclamptic group: 61% (56-69) vs 66% (63-71)
      (p = 0.037). At inclusion, blood pressures were significantly higher in the
      severe preeclamptic group compared with the control group, whereas cardiac output
      and transcranial Doppler readings were similar. Five minutes after the MgSO4
      bolus infusion, a median increase of 8.6% (3.2-18.1) in rcSO2 was observed (p =
      0.007), reaching values of the control group that were maintained up to 6 hours.
      Blood pressures and systolic velocities of the middle cerebral artery
      significantly decreased (p < 0.01) after the MgSO4 bolus, whereas cardiac output
      did not change. The percentage increase in rcSO2 was negatively correlated to the
      mean blood pressure (r = 0.60, p < 0.0001). CONCLUSION: Cerebral oxygenation
      impairment can be detected by near-infrared spectroscopy monitoring in severe
      preeclamptic parturients. These results suggested the presence of disorders in
      cerebral microcirculation and/or changes in cerebral oxygenation. MgSO4 infusion
      in patients with severe preeclampsia restored rcSO2 to control levels with no
      systemic side effects. Further studies are needed to confirm the usefulness of
      near-infrared spectroscopy monitoring in patients with preeclampsia and to assess
      the action of other antihypertensive therapies on rcSO2.

PMID- 25072764
TI  - Using the number needed to treat to assess appropriate antimicrobial therapy as a
      determinant of outcome in severe sepsis and septic shock.
AB  - OBJECTIVE: To assess appropriate antimicrobial therapy as an outcome determinant
      in severe sepsis and septic shock using the number needed to treat. DESIGN:
      Single-center cohort study (January 2008 to December 2012). SETTING: One thousand
      two hundred fifty-bed academic hospital. PATIENTS: Two thousand five hundred
      ninety-four patients with positive blood culture. INTERVENTIONS: We
      retrospectively identified patients with severe sepsis or septic shock.
      Inappropriate antimicrobial treatment was defined as an antimicrobial regimen
      that lacked in vitro activity against the isolated pathogen. Information
      regarding demographics, severity of illness, comorbidities, microbiology, and
      antimicrobial treatment was recorded. Logistic regression was used to identify
      risk factors for hospital mortality and inappropriate treatment. MEASUREMENTS AND
      MAIN RESULTS: Seven hundred eighty-seven patients (30.3%) were nonsurvivors.
      Inappropriate antimicrobial treatment had the greatest adjusted odds ratio for
      hospital mortality (adjusted odds ratio, 3.4; 95% CI, 2.8-4.1; p < 0.001).
      Multivariate logistic regression analysis identified resistance to cefepime,
      resistance to meropenem, presence of multidrug resistance, nonabdominal surgery,
      and prior antibiotic use as being independently associated with the
      administration of inappropriate antimicrobial treatment. For the entire cohort,
      the number needed to treat with appropriate antimicrobial therapy to prevent one
      patient death was 4.0 (95% CI, 3.7-4.3). The prevalence-adjusted pathogen
      specific number needed to treat (PNNT) with appropriate antimicrobial therapy to
      prevent one patient death was lowest for multidrug-resistant bacteria (PNNT = 20)
      followed by Candida species (PNNT = 34), methicillin-resistant Staphylococcus
      aureus (PNNT = 38), Pseudomonas aeruginosa (PNNT = 38), Escherichia coli (PNNT =
      40), and methicillin-susceptible S. aureus (PNNT = 47). CONCLUSIONS: Our results
      support the importance of appropriate antimicrobial treatment as a determinant of
      outcome in patients with severe sepsis and septic shock. Our analyses suggest
      that improved targeting of empiric antimicrobials for multidrug-resistant
      bacteria, Candida species, methicillin-resistant S. aureus, and P. aeruginosa
      would have the greatest impact in reducing mortality from inappropriate
      antimicrobial treatment in patients with severe sepsis and septic shock.

PMID- 25072765
TI  - Inhalation exposure to 1,2-dichloropropane: Distribution of blood and tissue
      concentrations of 1,2-dichloropropane in rats during and after exposure.
AB  - The present investigation was undertaken to determine the distribution and
      accumulation of 1,2-dichloropropane (DCP) in the blood, lung, liver, kidney, and
      abdominal fat of rats during and after inhalation exposure. Male rats were
      exposed to 80 or 500 ppm (v/v) DCP vapor for 360 min and the concentrations of
      DCP in the blood and tissues during the inhalation exposure period and after the
      end of the exposure period were measured. DCP accumulation in the abdominal fat
      was much greater than that in the blood and other tissues. Eighteen hours after
      the end of inhalation exposure, DCP could still be detected in the abdominal fat
      in the 80-ppm group, and in the blood, liver, kidney, and abdominal fat in the
      500-ppm group. Our results are valuable data pertaining to the pharmacokinetics
      of DCP and to human health risk assessment of exposure to DCP vapor by
      inhalation.

PMID- 25072766
TI  - Isolation and characterization of a Lysinibacillus strain B1-CDA showing
      potential for bioremediation of arsenics from contaminated water.
AB  - The main objective of this study was to identify and isolate arsenic resistant
      bacteria that can be used for removing arsenic from the contaminated environment.
      Here we report a soil borne bacterium, B1-CDA that can serve this purpose. B1-CDA
      was isolated from the soil of a cultivated land in Chuadanga district located in
      the southwest region of Bangladesh. The morphological, biochemical and 16S rRNA
      analysis suggested that the isolate belongs to Lysinibacillus sphaericus. The
      minimum inhibitory concentration (MIC) value of the isolate is 500 mM (As) as
      arsenate. TOF-SIMS and ICP-MS analysis confirmed intracellular accumulation and
      removal of arsenics. Arsenic accumulation in cells amounted to 5.0 mg g(-1) of
      the cells dry biomass and thus reduced the arsenic concentration in the
      contaminated liquid medium by as much as 50%. These results indicate that B1-CDA
      has the potential for remediation of arsenic from the contaminated water. We
      believe the benefits of implementing this bacterium to efficiently reduce arsenic
      exposure will not only help to remove one aspect of human arsenic poisoning but
      will also benefit livestock and native animal species. Therefore, the outcome of
      this research will be highly significant for people in the affected area and also
      for human populations in other countries that have credible health concerns as a
      consequence of arsenic-contaminated water.

PMID- 25072767
TI  - Reducing the mobility of arsenic in brownfield soil using stabilised zero-valent
      iron nanoparticles.
AB  - The use of nanoscale zero-valent iron (nZVI) as a new tool for the treatment of
      polluted soils and groundwater has received considerable attention in recent
      years due to its high reactivity, in situ application and cost-effectiveness. The
      objectives of this study were to investigate the effectiveness of using a
      commercial stabilised suspension of nZVI to immobilise As in brownfield soil and
      to investigate its impact on Fe availability in the treated soil. The
      phytotoxicities of the soil samples were also evaluated using a germination test
      with two plant species: barley (Hordeum vulgare L) and common vetch (Vicia sativa
      L). Two doses of the commercial nZVI suspension were studied, 1% and 10%, and two
      soil-nanoparticle interaction times, 72 h and 3 mo, were used to compare the
      stabilities of the soils treated with nZVI. The As availability was evaluated
      using a sequential extraction procedure and the toxicity characteristics leaching
      procedure (TCLP) test. The application of nZVI significantly decreased the
      availability of As in the soil. The immobilisation of As was more effective and
      more stable over time with the 10% dose than with the 1% dose of the commercial
      nZVI suspension. The application of nZVI did not induce an important increase in
      Fe mobility because the Fe leachability was less than 2 mg L(-1) over the time
      period studied. The lower availability of As in the soil led to a decrease in the
      phytotoxicity of the soil to barley and vetch germination. Thus, the proposed
      nanotechnology could be a potential alternative for the in situ remediation of As
      polluted soils and could be combined with remediation processes where plants are
      involved.

PMID- 25072768
TI  - Effects of extracellular polymeric substances on the bioaccumulation of mercury
      and its toxicity toward the cyanobacterium Microcystis aeruginosa.
AB  - This investigation examines how extracellular polymeric substances (EPSs) and
      environmental factors affect the bioaccumulation and toxicity of inorganic
      mercury (+2 oxidation state, Hg(II)) using a culture of Microcystis aeruginosa,
      which dominates eutrophic reservoir populations. The identified EPSs were
      classified as carbohydrates and proteins. Evaluation of the bioaccumulation of
      Hg(II) in cells by multiple regression analysis reveals that the concentration of
      EPSs in filtrate, the initial concentration of Hg(II) in medium, and the culture
      age significantly affected the amount of Hg(II) accumulated. Composition profiles
      revealed that the concentrations of soluble carbohydrates were significantly
      higher in Hg(II)-accumulated cells than in the control ones. Preliminary results
      based on scanning electron microscopic (SEM) map investigations suggest that most
      of the Hg(II) was accumulated in the cytoplasm (intracellular). Additionally, the
      effective concentrations (EC50) of Hg(II) that inhibit the growth of M.
      aeruginosa were 38.6 MUg L(-1) in the logarithmic phase and 17.5 MUg L(-1) in the
      stationary phase. As expected, the production of more EPSs in the logarithmic
      phase typically implies higher EC50 values because EPSs may be regarded as a
      protective barrier of cells against an external Hg(II) load, enabling them to be
      less influenced by Hg(II).

PMID- 25072769
TI  - Oxidation of Ni(II)-cyano and Co(III)-cyano complexes by Ferrate(VI): effect of
      pH.
AB  - Free cyanide (CN(-)) and metal-cyanide complexes (tetracyanonickelate(II)),
      Ni(CN)4(2-) and hexacyanocobaltate(III)), Co(CN)6(3-) are common constituents of
      effluents of mining, coal gasification, and petroleum refining. This article
      presents the degradation of Ni(CN)4(2-) and Co(CN)6(3-) by ferrate(VI)
      (Fe(VI)O4(2-), Fe(VI)) in alkaline media. The effect of pH (9.0-11.0) and
      reactant molar ratios on the degradation of the cyanide complexes was
      investigated. The removal of Ni(CN)4(2-) ion in 200 min was found to be > 90% at
      pH 9.0; forming cyanate (NCO(-)) ions as the stoichiometric products
      ([Fe(VI)]:[Total CN(-)] = [Fe(VI)]:[NCO(-)] ~ 1.0). The degradation efficiency
      decreased with an increase in pH from 9.0 to 11.0. Comparatively, the Co(CN)6(3-)
      ion could be degraded only up to 10% in 200 min at pH 9.0 and the final oxidized
      products were nitrite and nitrate ions. The oxidation efficiency of removing
      Co(CN)6(3-) did not vary significantly with pH. Fe(VI) consumptions as a result
      of the oxidation of free cyanide and metal-cyanides and their products are
      compared and discussed.

PMID- 25072770
TI  - Accumulation and distribution of macroelements in the organs of Phalaris
      arundinacea L.: Implication for phytoremediation.
AB  - The aim of this study was to assess nutrient and alkali metal accumulation and
      their distribution in the organs of Phalaris arundinacea and relations between
      environmental macroelement concentrations and accumulation in plant tissues. The
      content of N, P, K, Ca, Mg and Na in water, bottom sediments and different organs
      of Phalaris arundinacea from the Bystrzyca River (Lower Silesia) was determined.
      The organs of the reed canary grass contained relatively high amounts of
      macroelements and differed significantly in their accumulation. All macroelements
      other than Na were accumulated in the highest amounts in aboveground,
      photosynthetic tissues. Phalaris arundinacea is an Na and Ca excluder plant and
      an N, P, Mg and K accumulator. Transport efficiency from bottom sediments to
      plant roots was higher than between plant organs. Nitrogen, P and K are taken up
      actively while Ca passively. The high translocation ratio of nutrients,
      particularly for Ca, Mg, K and N, makes the reed canary grass suitable for
      nutrient phytoextraction from water and bottom sediments of eutrophic lakes and
      rivers. Bottom sediments can be considered the primary source of Ca for Phalaris
      arundinacea. 

PMID- 25072771
TI  - Selenium in brown bears (Ursus arctos) from Croatia: Relation to cadmium and
      mercury.
AB  - Muscle (n = 111), liver (n = 111), and kidney cortex (n = 101) samples from brown
      bears (Ursus arctos) were collected in the 2009 and 2010 hunting seasons in
      Croatia and analysed for selenium (Se), cadmium (Cd), and total mercury (Hg). The
      aim was to assess the levels of these elements according to age, sex, and season
      of collection, and to investigate possible Se/Cd and Se/Hg interactions. Median
      Se concentrations were 0.139 MUg/g in muscle, 0.409 MUg/g in liver and 1.75 MUg/g
      wet mass in kidney cortex. Median Cd and Hg were 0.0078 and 0.0018 MUg/g in
      muscle, 1.09 and 0.031 MUg/g in liver, and 16.5 and 0.206 MUg/g wet mass in the
      renal cortex, respectively. Se/Cd molar ratios were less than 1 in the kidney
      cortex, and close to or above 1 in liver and muscle, respectively. Toxic Cd and
      Hg correlated with Se in all of the studied tissues. Sex differences were found
      for all three elements (except Se in liver), with females having higher tissue
      concentration than males. Only Cd showed age-dependence. Bear samples collected
      in fall had higher Se in muscles, and Hg in muscles and liver compared to samples
      collected in spring. Element concentrations in brown bear tissues were within the
      range of previously reported studies. Bear meat is considered a rich source of
      Se, safe for consumption with regard to its Cd and Hg content. According to the
      molar ratio and correlation results, we assume that Se binding is not the primary
      detoxification pathway for Cd and Hg in brown bears.

PMID- 25072772
TI  - Study of nitrogen pollution in Croatia by moss biomonitoring and Kjeldahl method.
AB  - During the summer and autumn of 2006 moss samples were collected from 98 sampling
      sites evenly distributed all over the territory of Croatia. Moss sampling was
      repeated in 2010 when additional sampling sites were added and a total of 121
      samples were collected. Kjeldahl method was used to determine the nitrogen
      content in the samples. Descriptive statistics and distribution maps were
      prepared. Data obtained from these two surveys were compared, and additional
      comparison was done with data obtained from similar studies in neighbouring
      countries and Finland as a clean area. The median value of N content in the
      samples collected in 2006 is 1.60% and varies from 0.79% to 3.16%. The content of
      N in samples collected in 2010 ranges between 0.71% and 2.93% with the median
      value of 1.49%. High contents of N (2.32% - 3.17%) were found in the regions of
      Slavonia, Podravina, Posavina and cities Zagreb and Sisak as a result of
      agricultural activities, industry and traffic. 

PMID- 25072773
TI  - Geochemical barriers for environment protection and recovery of nonferrous
      metals.
AB  - A study of natural minerals, ore tailings and their products as materials for
      artificial geochemical barriers is presented. In particular, it focuses on
      interaction between calcite and dolomite and sulfate solutions containing nickel,
      copper and iron under static conditions. Calcite of -0.1 mm fraction has been
      shown to perform well as a barrier when added to water phases of tailing dumps
      and natural reservoirs. Experiments under dynamic conditions have revealed a high
      potential of thermally activated copper-nickel tailings as barriers. After a 500
      day precipitating period on a geochemical barrier, the contents of nickel and
      copper in ore dressing tailings were found to increase 12- and 28-fold,
      respectively. An effective sorbent of copper, iron and nickel ions is a brucite
      based product of hydrochloric acid treatment of vermiculite ore tailings. Its
      sorption capacity can be essentially increased through thermal activation. 

PMID- 25072774
TI  - Transport and fate of silver as polymer-stabilised nanoparticles and ions in a
      pilot wastewater treatment plant, followed by sludge digestion and disposal of
      sludge/soil mixtures: A case study.
AB  - A case study of transport and changes in properties of polymer-stabilised Ag NPs
      is presented in this paper investigating their interaction in different treatment
      steps within a fully realistic pilot wastewater treatment plant (WWTP), in
      anaerobic digested sludge, and in soil/sludge mixtures. The fate of the same Ag
      NPs was tracked in these environments, hence taking the history of the Ag NPs
      into account. The results show that most of the Ag NPs end up in the sludge (80
      100%), also after anaerobically digestion. Furthermore, the fraction of silver in
      the supernatant was very low after 48 h incubation with silver-containing
      digested sludge mixed with different soil types. However, when Ag NPs were added
      directly to the sludge/soil mixture, soluble silver was present in the
      supernatant with sandy soil, but not with clayey soil. In all, generated findings
      show that risk assessments and toxicological studies of Ag NPs suspensions must
      take into account possible chemical and particle transformations upon
      environmental entry, as silver in general become less soluble when transported to
      WWTPs and interacting with sludge, and soil.

PMID- 25072775
TI  - Ultrasonic oil recovery and salt removal from refinery tank bottom sludge.
AB  - The oil recovery and salt removal effects of ultrasonic irradiation on oil
      refinery tank bottom sludge were investigated, together with those of direct
      heating. Ultrasonic power, treatment duration, sludge-to-water ratio, and initial
      sludge-water slurry temperature were examined for their impacts on sludge
      treatment. It was found that the increased initial slurry temperature could
      enhance the ultrasonic irradiation performance, especially at lower ultrasonic
      power level (i.e., 21 W), but the application of higher-power ultrasound could
      rapidly increase the bulk temperature of slurry. Ultrasonic irradiation had a
      better oil recovery and salt removal performance than direct heating treatment.
      More than 60% of PHCs in the sludge was recovered at an ultrasonic power of 75 W,
      a treatment duration of 6 min, an initial slurry temperature of 25 degrees C, and
      a sludge-to-water ratio of 1:4, while salt content in the recovered oil was
      reduced to <5 mg L(-1), thereby satisfying the salt requirement in refinery
      feedstock oil. In general, ultrasonic irradiation could be an effective method in
      terms of oil recovery and salt removal from refinery oily sludge, but the
      separated wastewater still contains relatively high concentrations of PHCs and
      salt which requires proper treatment.

PMID- 25072776
TI  - Aerobic degradation of petroleum refinery wastewater in sequential batch reactor.
AB  - The aim of the present work was to study the effect of various parameters
      affecting the treatment of raw petroleum refinery wastewater (PRW) having
      chemical oxygen demand (COD) of 350 mg L(-1) and total organic carbon (TOC) of 70
      mg L(-1) in sequential batch reactor (SBR). Effect of hydraulic retention time
      (HRT) was studied in instantaneous fill condition. Maximum COD and TOC removal
      efficiencies were found to be 80% and 84%, respectively, for fill phase of 2 h
      and react phase of 2 h with fraction of SBR being filled with raw PRW in each
      cycle being 0.4. Effect of parameters was studied in terms of settling
      characteristic of treated slurry. Kinetics of treatment process has been studied.
      FTIR and UV-visible analysis of PRW before and after treatment have been
      performed so as to understand the degradation mechanism.

PMID- 25072777
TI  - The effects of naturally occurring acids on the surface properties of chrysotile
      asbestos.
AB  - Chrysotile asbestos is considered an environmental health hazard. It is
      postulated that the surface of chrysotile, with its inherent positive charge and
      chemical content of trace transition metals within the mineral is a causative
      factor of the concern. Weathering may reduce the negative health effects of
      chrysotile asbestos, by alteration of the outer brucite layer of the chrysotile.
      To assess the changes in the surface properties of chrysotile asbestos by
      simulated weathering, chrysotile was treated with oxalic, hydrochloric, and
      carbonic acids. Naturally occurring chrysotile, from a mine site and
      serpentinitic stream sediments from the Sumas River were analyzed and compared.
      Oxalic acid, a chelating acid, was the most effective at extracting the majority
      of the trace elements present in the chrysotile, reducing their positive surface
      charge and producing visible changes at the surface of the fibers as shown by
      Field Emission Scanning Electron Microsopy (FESEM). Carbonic acid had little
      effect on the surface properties. Stream environments had minor detectable
      effects on the surface properties on the chrysotile stream sediments. 

PMID- 25072778
TI  - Whole serum 3D LC-nESI-FTMS quantitative proteomics reveals sexual dimorphism in
      the milieu interieur of overweight and obese adults.
AB  - Linking gender-specific differences to the molecular etiology of obesity has been
      largely based on genomic and transcriptomic evidence lacking endophenotypic
      insight and is not applicable to the extracellular fluid compartments, or the
      milieu interieur, of the human body. To address this need, this study profiled
      the whole serum proteomes of age-matched nondiabetic overweight and obese females
      (n = 28) and males (n = 31) using a multiplex design with pooled biological and
      technical replicates. To bypass basic limitations of immunodepletion-based
      strategies, subproteome enrichment by size-exclusion chromatography (SuPrE-SEC)
      followed by iTRAQ 2D-LC-nESI-FTMS analysis was used. The study resulted in the
      reproducible analysis of 2472 proteins (peptide FDR < 5%, q < 0.05). A total of
      248 proteins exhibited significant modulation between men and women (p < 0.05)
      that mapped to pathways associated with beta-estradiol, lipid and prostanoid
      metabolism, vitamin D function, immunity/inflammation, and the complement and
      coagulation cascades. This novel endophenotypic signature of gender-specific
      differences in whole serum confirmed and expanded the results of previous
      physiologic and pharmacologic studies exploring sexual dimorphism at the genomic
      and transcriptomic level in tissues and cells. Conclusively, the multifactorial
      and pleiotropic nature of human obesity exhibits sexual dimorphism in the
      circulating proteome of importance to clinical study design. 

PMID- 25072779
TI  - Pregabalin serum levels in apprehended drivers.
AB  - Pregabalin is a medicinal drug used mainly for the treatment of epilepsy and
      neuropathic pain. It has been shown to possess an abuse potential and in recent
      years some reports of illegal use have been published. In order to further
      evaluate the extent and nature of pregabalin abuse, serum pregabalin levels of
      drivers apprehended for driving under the influence of drugs (DUID) in Finland in
      2012 were assessed. The samples were analysed by an LC-MS/MS system and the
      results were evaluated in relation to the typical therapeutic range of pregabalin
      as well as the age and gender of the driver. Pregabalin was detected in 206
      samples in the study period. The median (range) serum concentration was 6.2 (0.68
      111.6)mg/L. In nearly 50% of the cases the serum concentration was above the
      typical therapeutic range. In most of the cases the driver had also taken other
      drugs besides pregabalin, the mean number of concomitantly taken drugs being
      four. Our data indicate that pregabalin is being used at high doses, probably for
      recreational purposes. The vast majority of the drivers positive for pregabalin
      in our study material had used pregabalin as a part of a spectrum of psycho
      active drugs and thus qualified as probable drug abusers. In these cases
      pregabalin probably contributed to their driving impairment but to what extent
      remained unclear in this study. 

PMID- 25072781
TI  - Linking Cr3 triangles through phosphonates and lanthanides: synthetic,
      structural, magnetic and EPR studies.
AB  - The preparation and structural characterisation of five 3d-4f mixed metal
      phosphonate cages with general formula [Cr(III)6Ln(III)2(MU3
      O)2(H2O)2(O3P(t)Bu)4(O2C(t)Bu)12(HO(i)Bu)2((i)PrNH2)2] where Ln(III) = La, 1; Tb,
      3; Dy, 4; Ho, 5 and [Cr(III)6Gd(III)2(MU3
      O)2(H2O)2(O3P(t)Bu)4(O2C(t)Bu)12(HO(i)Bu)4] (2) are reported. The structure
      contains two oxo-centred {Cr3} triangles, bridged by phosphonates and
      lanthanides. The magnetic behaviour of 1 has been modelled as two non-interacting
      isosceles triangles, involving two antiferromagnetic interactions (J1 = -8.8 cm(
      1)) with a smaller ferromagnetic interaction for the unique edge of the triangle
      (J2 = +1.3 cm(-1)) giving an isolated S = 3/2 ground state per triangle. The
      quartet ground state has been proven through simulation of electron paramagnetic
      resonance (EPR) spectra obtained at the X- and Q-band. EPR simulations have also
      resulted in the introduction of small single-ion Zero Field Splitting (ZFS)
      parameters D = +/-0.19 cm(-1) and rhombic term E = +/-0.02 cm(-1), which are
      consistent with strong exchange limit calculations for an isolated S = 3/2 (D =
      +/-0.22 and E = +/-0.018 cm(-1)).

PMID- 25072780
TI  - Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose
      therapy with stem cell transplantation in poor-risk patients with diffuse large B
      cell lymphoma.
AB  - We evaluated the safety and efficacy of standard-dose yttrium-90 (Y(90))
      ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide,
      cytarabine, and melphalan) after first-line induction treatment in young patients
      with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov:
      NCT00689169). Seventy-five high-risk (>=2 International Prognostic Index [IPI]
      factors) consecutive DLBCL patients (<=65 years old) in complete remission (CR)
      or partial remission (PR) after rituximab chemotherapy were treated with Y(90)
      ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell
      transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients,
      71 underwent ASCT and were eligible for analysis. Median time to reach a
      neutrophil count of >500/MUL and platelet count of >20,000/MUL was 11 days.
      Mucositis >=3 (51%) occurred in most patients. Other adverse events were similar
      to those seen with BEAM alone. The overall response rate was 86%; 59 patients
      (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS),
      overall survival (OS), and disease-free survival were 79%, 83%, and 91%,
      respectively. Disease status (CR/PR) and positron emission tomography (PET)
      findings before transplantation did not predict treatment failure. The IPI (2
      versus >2) and maximum tumor diameter of >=10 cm at diagnosis appeared to be
      prognosis factors for OS but not for EFS. Adding Y(90) ibritumomab tiuxetan to
      BEAM is safe and does not increase transplantation-related toxicity. First-line
      consolidation with Y(90) ibritumomab tiuxetan and high-dose chemotherapy induced
      high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET
      status after induction treatment and warrants a randomized study. 

PMID- 25072782
TI  - Carbon monoxide induces heme oxygenase-1 to modulate STAT3 activation in
      endothelial cells via S-glutathionylation.
AB  - IL-6/STAT3 pathway is involved in a variety of biological responses, including
      cell proliferation, differentiation, apoptosis, and inflammation. In our present
      study, we found that CO releasing molecules (CORMs) suppress IL-6-induced STAT3
      phosphorylation, nuclear translocation and transactivity in endothelial cells
      (ECs). CO is a byproduct of heme degradation mediated by heme oxygenase (HO-1).
      However, CORMs can induce HO-1 expression and then inhibit STAT3 phosphorylation.
      CO has been found to increase a low level ROS and which may induce protein
      glutathionylation. We hypothesized that CORMs increases protein glutathionylation
      and inhibits STAT3 activation. We found that CORMs increase the intracellular
      GSSG level and induce the glutathionylation of multiple proteins including STAT3.
      GSSG can inhibit STAT3 phosphorylation and increase STAT3 glutathionylation
      whereas the antioxidant enzyme catalase can suppress the glutathionylation.
      Furthermore, catalase blocks the inhibition of STAT3 phosphorylation by CORMs
      treatment. The inhibition of glutathione synthesis by BSO was also found to
      attenuate STAT3 glutathionylation and its inhibition of STAT3 phosphorylation. We
      further found that HO-1 increases STAT3 glutathionylation and that HO-1 siRNA
      attenuates CORM-induced STAT3 glutathionylation. Hence, the inhibition of STAT3
      activation is likely to occur via a CO-mediated increase in the GSSG level, which
      augments protein glutathionylation, and CO-induced HO-1 expression, which may
      enhance and maintain its effects in IL-6-treated ECs. 

PMID- 25072783
TI  - Temperate pine barrens and tropical rain forests are both rich in undescribed
      fungi.
AB  - Most of fungal biodiversity on Earth remains unknown especially in the unexplored
      habitats. In this study, we compared fungi associated with grass (Poaceae) roots
      from two ecosystems: the temperate pine barrens in New Jersey, USA and tropical
      rain forests in Yunnan, China, using the same sampling, isolation and species
      identification methods. A total of 426 fungal isolates were obtained from 1600
      root segments from 80 grass samples. Based on the internal transcribed spacer
      (ITS) sequences and morphological characteristics, a total of 85 fungal species
      (OTUs) belonging in 45 genera, 23 families, 16 orders, and 6 classes were
      identified, among which the pine barrens had 38 and Yunnan had 56 species, with
      only 9 species in common. The finding that grass roots in the tropical forests
      harbor higher fungal species diversity supports that tropical forests are fungal
      biodiversity hotspots. Sordariomycetes was dominant in both places but more
      Leotiomycetes were found in the pine barrens than Yunnan, which may play a role
      in the acidic and oligotrophic pine barrens ecosystem. Equal number of
      undescribed fungal species were discovered from the two sampled ecosystems,
      although the tropical Yunnan had more known fungal species. Pine barrens is a
      unique, unexplored ecosystem. Our finding suggests that sampling plants in such
      unexplored habitats will uncover novel fungi and that grass roots in pine barrens
      are one of the major reservoirs of novel fungi with about 47% being undescribed
      species. 

PMID- 25072785
TI  - Analysis of protein carbonylation--pitfalls and promise in commonly used methods.
AB  - Oxidation of proteins has received a lot of attention in the last decades due to
      the fact that they have been shown to accumulate and to be implicated in the
      progression and the pathophysiology of several diseases such as Alzheimer,
      coronary heart diseases, etc. This has also resulted in the fact that research
      scientists are becoming more eager to be able to measure accurately the level of
      oxidized protein in biological materials, and to determine the precise site of
      the oxidative attack on the protein, in order to get insights into the molecular
      mechanisms involved in the progression of diseases. Several methods for measuring
      protein carbonylation have been implemented in different laboratories around the
      world. However, to date no methods prevail as the most accurate, reliable, and
      robust. The present paper aims at giving an overview of the common methods used
      to determine protein carbonylation in biological material as well as to highlight
      the limitations and the potential. The ultimate goal is to give quick tips for a
      rapid decision making when a method has to be selected and taking into
      consideration the advantage and drawback of the methods.

PMID- 25072786
TI  - [Extrapulmonary tuberculosis in prisons: the need to adapt to changing
      realities].

PMID- 25072784
TI  - Obesity indexes and total mortality among elderly subjects at high cardiovascular
      risk: the PREDIMED study.
AB  - BACKGROUND: Different indexes of regional adiposity have been proposed for
      identifying persons at higher risk of death. Studies specifically assessing these
      indexes in large cohorts are scarce. It would also be interesting to know whether
      a dietary intervention may counterbalance the adverse effects of adiposity on
      mortality. METHODS: We assessed the association of four different anthropometric
      indexes (waist-to-height ratio (WHtR), waist circumference (WC), body mass index
      (BMI) and height) with all-cause mortality in 7447 participants at high
      cardiovascular risk from the PREDIMED trial. Forty three percent of them were men
      (55 to 80 years) and 57% were women (60 to 80 years). All of them were initially
      free of cardiovascular disease. The recruitment took place in 11 recruiting
      centers between 2003 and 2009. RESULTS: After adjusting for age, sex, smoking,
      diabetes, hypertension, intervention group, family history of coronary heart
      disease, and leisure-time physical activity, WC and WHtR were found to be
      directly associated with a higher mortality after 4.8 years median follow-up. The
      multivariable-adjusted HRs for mortality of WHtR (cut-off points: 0.60, 0.65,
      0.70) were 1.02 (0.78-1.34), 1.30 (0.97-1.75) and 1.55 (1.06-2.26). When we used
      WC (cut-off points: 100, 105 and 110 cm), the multivariable adjusted Hazard
      Ratios (HRs) for mortality were 1.18 (0.88-1.59), 1.02 (0.74-1.41) and 1.57 (1.19
      2.08). In all analyses, BMI exhibited weaker associations with mortality than WC
      or WHtR. The direct association between WHtR and overall mortality was consistent
      within each of the three intervention arms of the trial. CONCLUSIONS: Our study
      adds further support to a stronger association of abdominal obesity than BMI with
      total mortality among elderly subjects at high risk of cardiovascular disease. We
      did not find evidence to support that the PREDIMED intervention was able to
      counterbalance the harmful effects of increased adiposity on total mortality.
      TRIAL REGISTRATION: Controlled-Trials.com ISRCTN35739639.

PMID- 25072787
TI  - [A descriptive study of substance abuse and mental health disorders in intimate
      partner violence abusers in prison].
AB  - OBJECTIVE: To obtain data on substance abuse and mental disorders amongst a
      population of inmates imprisoned for gender violence. DESIGN: 106 intimate
      partner violence offenders were recruited in our study, all of whom were prison
      inmates. The study is descriptive and statistical comparison of percentages was
      used. RESULTS: the percentage of substance abuse was 61.3%; most of which
      consisted of alcohol and cocaine. According to DSM-IV R, 25.5% of the inmates had
      at least one psychiatric diagnosis at the time when entering prison: 11.3%
      adjustment disorder with depressed mood, 6.6% personality disorders, 2.8%
      psychosis, 1.9% major depressive disorder, 1.9% bipolar disorder and 1.9% psycho
      organic disorder were encountered. The average age of the men of the sample was
      forty years old. The most common nationality was Spanish. The percentage of
      immigrants was significant greater than the global percentage of the general
      population. The percentage of global substance consumption and psychopathologic
      problems is greater than data obtained in IPV from other populations, like
      samples of men charged by their partners with gender violence. CONCLUSIONS:
      depressive symptoms, personality disorders, alcohol and cocaine consumption need
      to be investigated as gender violence risk markers in Spain. Attention should be
      paid to the role of consumption prevention when entering prison.

PMID- 25072788
TI  - [Prevalence of chronic diseases and risk factors among the Spanish prison
      population].
AB  - BACKGROUND: chronic diseases are responsible for 60% of deaths and 75% of
      spending on public health. There are few works on the prevalence of this type of
      pathology in prison. OBJECTIVE: Describe the prevalence of chronic major diseases
      in the population and the major risk factors observed. METHODS: Multicenter
      transversal descriptive study. The sample size was 1,170 people, who were
      selected through sampling stratified with simple allocation by strata among 9
      prisons in the country. There were interviews and physical examinations between
      May and June 2013. Variables were collected: socio-demographic, diagnostic,
      anthropometric, clinical-analytical and risk factors. A descriptive and
      subsequent comparative analysis was carried out using non-parametric tests for
      quantitative variables using the Mann-Whitney test and a Ji-square test for
      categorical variables. Subsequently, binary logistic regression models to
      evaluate the influence of factors of risk in major pathologies. The manuscript
      was approved by the Ethics Committee for clinical research of the University
      General Hospital of Castellon. RESULTS: 1 of every 2 inmates has some type of
      chronic disease out of the 1,077 participated (92.1). Median age of 37.4 years
      IQR (30.0 to 44.8). 95 males, 40.6 foreigners. Prevalence: dyslipidemias (34.8);
      arterial hypertension (17.8); Diabetes (5.3); asthma (4.6); COPD (2.2); ischaemic
      heart disease (1.8) and (1.5) cardio-circulatory pathologies. Main risk factors:
      smoking, obesity, abdominal fat distribution, consumption of cocaine and age.
      CONCLUSIONS: It would be interesting to establish early diagnosis, encourage
      giving up smoking, and physical activity and dietary advice to combat the major
      modifiable risk factors.

PMID- 25072789
TI  - New times for migrants' health in Europe.
AB  - Patterns of migration can change greatly over time, with the size and composition
      of migrant populations reflecting both, current and historical patterns of
      migration flows. The recent economic crisis has caused a decrease on migration
      flows towards the most affected areas, as well as cut offs in health
      interventions addressed to migrants. The objective of this paper is to review
      available data about interventions on migrants' health in Europe, and to describe
      changes in migrant health policies across Europe after the economic crisis, that
      can have a negative effect in their health status. Although migrants have the
      right to health care under legal settlements issued by the EU, there is no a
      standard European approach to offer health care to migrants, since; policies in
      each EU Member State are developed according to specific migrant experience,
      political climate, and attitudes towards migration. Migrants use to face greater
      health problems and major health care access barriers, compared with their
      counterparts from the EU. Therefore, migrant health policies should focus in
      protects this vulnerable group, especially during economic hardship, taking into
      account economic and socio-demographic risk factors. There is an especial need
      for research in the cost-effectiveness of investing in the health care of the
      migrant population, demonstrating the benefit of such, even in the health of the
      European native population, and the need for constant intervention despite of
      resource constraints. 

PMID- 25072790
TI  - [Tuberculous gumma or metastatic tuberculous abscess as initial diagnosis of
      tuberculosis in an immunocompetent patient: an unusual presentation].
AB  - BACKGROUND AND OBJECTIVES: Tuberculous cold abscesses or gumma are an unusual
      form of tuberculosis. We report a case of gumma as initial diagnosis of
      disseminated tuberculosis. METHOD: This case was studied in 2012 in Barcelona (
      Spain). Source data was compiled from the electronic clinical records, hospital
      reports and additional diagnostic testing. RESULTS: Immunocompetent inmate, born
      in Cape Verde, living in Spain since the age of four. Positive tuberculin skin
      test. Initial examination without interest, but a palpable mass in lower back.
      Fine needle aspiration of the abscess was positive (PCR and Lowenstein) for M.
      tuberculosis. Computed tomography showed lung cavitary nodes in apical part and
      lung upper right side. After respiratory isolation, antituberculous therapy and
      an excellent evolution, the patient was discharged from hospital with
      disseminated tuberculosis diagnosis. DISCUSSION: It is advisable to monitor the
      injuries since, although rare, it may be secondary to Mycobacterium tuberculosis
      infection, mainly in inmuno-compromised populations and in immigrants coming from
      hyper-endemic tuberculosis areas.

PMID- 25072791
TI  - [Chronic dorsalgia that was found to be Pott's disease].

PMID- 25072792
TI  - Pharmacological characterization of the mechanisms involved in the vasorelaxation
      induced by progesterone and 17beta-estradiol on isolated canine basilar and
      internal carotid arteries.
AB  - Progesterone and 17beta-estradiol induce vasorelaxation through non-genomic
      mechanisms in several isolated blood vessels; however, no study has
      systematically evaluated the mechanisms involved in the relaxation induced by
      17beta-estradiol and progesterone in the canine basilar and internal carotid
      arteries that play a key role in cerebral circulation. Thus, relaxant effects of
      progesterone and 17beta-estradiol on KCl- and/or PGF2alpha-pre-contracted
      arterial rings were investigated in absence or presence of several
      antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl2
      was also determined. In both arteries progesterone (5.6-180 MUM) and 17beta
      estradiol (1.8-180 MUM): (1) produced concentration-dependent relaxations of KCl-
      or PGF2alpha-pre-contracted arterial rings; (2) the relaxations were unaffected
      by actinomycin D (10 MUM), cycloheximide (10 MUM), SQ 22,536 (100 MUM) or ODQ (30
      MUM), potassium channel blockers and ICI 182,780 (only for 17beta-estradiol). In
      the basilar artery the vasorelaxation induced by 17beta-estradiol was slightly
      blocked by tetraethylammonium (10mM) and glibenclamide (KATP; 10 MUM). In both
      arteries, progesterone (10-100 MUM), 17beta-estradiol (3.1-31 MUM) and nifedipine
      (0.01-1 MUM) produced a concentration-dependent blockade of the contraction to
      CaCl2 (10 MUM-10mM). These results suggest that progesterone and 17beta-estradiol
      produced relaxation in the basilar and internal carotid arteries by blockade of L
      type voltage dependent Ca(2+) channel but not by genomic mechanisms or production
      of cAMP/cGMP. Potassium channels did not play a role in the relaxation to
      progesterone in both arteries or in the effect of 17beta-estradiol in the
      internal carotid artery; meanwhile KATP channels play a minor role on the effect
      of 17beta-estradiol in the basilar artery.

PMID- 25072793
TI  - Current state of practice regarding testosterone supplementation therapy in men
      with prostate cancer.
AB  - Hypogonadal men are characterized by low serum testosterone and symptoms of low
      energy, decreased libido, and muscle mass as well as impaired concentration and
      sexual functioning. Men with prostate cancer (PCa) currently on active
      surveillance or post-therapy, have traditionally been excluded from management
      paradigms given the decade-old concern that testosterone caused PCa growth.
      However, there appears to be little or no relationship between serum testosterone
      concentration and PCa. Androgen action in the prostate has long been known to be
      affected by the kinetics of receptor saturation and, as such, testosterone beyond
      a certain baseline is unable to stimulate prostatic growth due to complete intra
      prostatic androgen receptor binding. Given this physiologic concept, many
      clinical investigators have begun to promote testosterone supplementation therapy
      (TST) as safe in men with PCa. This review examines the basics of testosterone
      physiology and summarizes the most recent findings on the use of TST in men with
      PCa on active surveillance and following treatment with external beam
      radiotherapy, brachytherapy and radical prostatectomy.

PMID- 25072794
TI  - Hemolysis exacerbates hyperfibrinolysis, whereas platelolysis shuts down
      fibrinolysis: evolving concepts of the spectrum of fibrinolysis in response to
      severe injury.
AB  - INTRODUCTION: We have recently identified a spectrum of fibrinolysis in response
      to injury, in which there is increased mortality in patients who have either
      excessive fibrinolysis (hyperfibrinolysis [HF]) or impaired fibrinolysis
      (shutdown). The regulation of the fibrinolytic system after trauma remains poorly
      understood. Our group's previous proteomic and metabolomic work identified
      elevated red blood cell (RBC) degradation products in trauma patients manifesting
      HF. We therefore hypothesized that hemolysis was contributory to the pathogenesis
      of HF. Given the central role of platelets in the cell-based model of
      coagulation, we further investigated the potential role of platelet lysis in
      mediation of the fibrinolytic system. METHODS: Red blood cells from healthy
      donors were frozen in liquid nitrogen and vortexed to create mechanical membrane
      disruption. Platelets were prepared in a similar fashion. Assays were performed
      with citrated whole blood mixed ex vivo with either RBC or platelet lysates.
      Tissue plasminogen activator (tPA) was then added to promote fibrinolysis,
      mimicking the tPA release from ischemic endothelium during hemorrhagic shock. The
      degree of fibrinolysis was evaluated with thromboelastography. To identify the
      mediators of the fibrinolysis system present in RBC and platelet lysates, these
      lysates were passed over immobilized tPA and plasminogen affinity columns to
      capture protein-binding partners from RBC or platelet lysates. RESULTS: The
      addition of 75 ng/mL of tPA to whole blood increased fibrinolysis from median 30
      min lysis of 1.4% (interquartile range [IQR], 0.9%-2.0%) to 8.9% (IQR, 6.5%
      11.5%). Red blood cell lysate with tPA increased fibrinolysis to 20.1% (IQR,
      12.5%-33.7%), which was nearly three times as much lysis as tPA alone (P <
      0.001). Conversely, the addition of platelet lysate decreased tPA-mediated
      fibrinolysis to 0.35% (IQR, 0.2%-0.8%; P < 0.001). Affinity chromatography
      coupled with tandem mass spectrometry identified a number of proteins not
      previously associated with regulation of fibrinolysis and trauma. CONCLUSION: Red
      blood cell lysate is a potent enhancer of fibrinolysis, whereas platelet lysate
      inhibits fibrinolysis. Intracellular proteins from circulating blood cells
      contain proteins that interact with the two key proteins of tPA-mediated
      fibrinolysis. Understanding the effect of tissue injury and shock on the lysis of
      circulating cells may provide insight to comprehending the spectrum of
      fibrinolysis in response to trauma.

PMID- 25072797
TI  - Origin of the high performance in GeTe-based thermoelectric materials upon Bi2Te3
      doping.
AB  - As a lead-free material, GeTe has drawn growing attention in thermoelectrics, and
      a figure of merit (ZT) close to unity was previously obtained via traditional
      doping/alloying, largely through hole carrier concentration tuning. In this
      report, we show that a remarkably high ZT of ~1.9 can be achieved at 773 K in
      Ge0.87Pb0.13Te upon the introduction of 3 mol % Bi2Te3. Bismuth telluride
      promotes the solubility of PbTe in the GeTe matrix, thus leading to a
      significantly reduced thermal conductivity. At the same time, it enhances the
      thermopower by activating a much higher fraction of charge transport from the
      highly degenerate Sigma valence band, as evidenced by density functional theory
      calculations. These mechanisms are incorporated and discussed in a three-band (L
      + Sigma + C) model and are found to explain the experimental results well.
      Analysis of the detailed microstructure (including rhombohedral twin structures)
      in Ge0.87Pb0.13Te + 3 mol % Bi2Te3 was carried out using transmission electron
      microscopy and crystallographic group theory. The complex microstructure explains
      the reduced lattice thermal conductivity and electrical conductivity as well. 

PMID- 25072796
TI  - Impact of religiosity on the sexual risk behaviors of young men who have sex with
      men.
AB  - Young men who have sex with men (YMSM), particularly Black YMSM, bear a
      disproportionate burden of new human immunodeficiency virus (HIV) infections in
      the United States. Several studies support the positive and protective role of
      religion in health and the prevention of morbidity and mortality. However, little
      empirical research has been conducted looking at religion with the context of
      YMSM and HIV prevention. We examined the impact of religious attendance and
      faithfulness on sexual risk among a community-based sample of 450 YMSM in Chicago
      ages 16 to 20. Participants were mostly racial/ethnic minorities, that is, Black
      (53.4%) and Latino (19.9%). Multivariate logistic regression indicated that
      faithfulness in combination with frequent formal religious attendance was
      associated with a decrease in reported number of unprotected anal sex acts,
      including unprotected receptive anal sex with male partners. These association
      trends were also found for the Black YMSM in our sample, suggesting that
      religious involvement and faithfulness is a potential protective factor for the
      acquisition of HIV among this high-risk population. 

PMID- 25072795
TI  - Treatment of tumors with vitamin E suppresses myeloid derived suppressor cells
      and enhances CD8+ T cell-mediated antitumor effects.
AB  - Vitamin E has been shown to have strong anticarcinogenic properties, including
      antioxidant characteristics, making it an ideal candidate for use in combination
      with immunotherapies that modify the tumor microenvironment. The tumor
      microenvironment contains immunosuppressive components, which can be diminished,
      and immunogenic components, which can be augmented by immunotherapies in order to
      generate a productive immune response. In the current study, we employ the alpha
      tocopherol succinate isomer of vitamin E to reduce immunosuppression by myeloid
      derived suppressor cells (MDSCs) as well as adoptive transfer of antigen-specific
      CD8+ T cells to generate potent antitumor effects against the HPV16 E7-expressing
      TC-1 tumor model. We show that vitamin E alone induces necrosis of TC-1 cells and
      elicits antitumor effects in TC-1 tumor-bearing mice. We further demonstrate that
      vitamin E reverses the suppression of T cell activation by MDSCs and that this
      effect is mediated in part by a nitric oxide-dependent mechanism. Additionally,
      treatment with vitamin E reduces the percentage of MDSCs in tumor loci, and
      induces a higher percentage of T cells, following T cell adoptive transfer.
      Finally, we demonstrate that treatment with vitamin E followed by E7-specific T
      cell adoptive transfer experience elicits potent antitumor effects in tumor
      bearing mice. Our data provide additional evidence that vitamin E has anticancer
      properties and that it has promise for use as an adjuvant in combination with a
      variety of cancer therapies. 

PMID- 25072798
TI  - Broad temperature plateau for thermoelectric figure of merit ZT>2 in phase
      separated PbTe0.7S0.3.
AB  - Thermoelectrics interconvert heat to electricity and are of great interest in
      waste heat recovery, solid-state cooling and so on. The efficiency of
      thermoelectric materials depends directly on the average ZT (dimensionless figure
      of merit) over a certain temperature range, which historically has been
      challenging to increase. Here we report that 2.5% K-doped PbTe0.7S0.3 achieves a
      ZT of >2 for a very wide temperature range from 673 to 923 K and has a record
      high average ZT of 1.56 (corresponding to a theoretical energy conversion
      efficiency of ~20.7% at the temperature gradient from 300 to 900 K). The
      PbTe0.7S0.3 composition shows spinodal decomposition with large PbTe-rich and PbS
      rich regions where each region exhibits dissimilar types of nanostructures. Such
      high average ZT is obtained by synergistically optimized electrical- and thermal
      transport properties via carrier concentration tuning, band structure engineering
      and hierarchical architecturing, and highlights a realistic prospect of wide
      applications of thermoelectrics. 

PMID- 25072799
TI  - Risk-based learning games improve long-term retention of information among school
      pupils.
AB  - Risk heightens motivation and, if used appropriately, may have the potential to
      improve engagement in the classroom. We have developed a risk-based learning game
      for school pupils in order to test whether such learning games can improve later
      recall of information. The study was performed during a series of public
      engagement workshops delivered by undergraduate students. Undergraduate
      neuroscience students delivered 90-minute science workshops to 9-10 year old
      school pupils (n = 448) that were divided into 'Risk', 'No risk' and 'Control'
      classes. 'Risk' classes received periodic multiple-choice questions (MCQs) during
      the workshops which required small teams of pupils to assign tokens to the
      answer(s) they believed to be correct. Tokens assigned to the correct answer were
      returned to the group and an equal number given back as a prize; tokens assigned
      to incorrect answers were lost. Participation was incentivised by the promise of
      a brain-related prize to the team with the most tokens at the end of the
      workshop. 'No risk' classes received MCQs without the risk component whilst the
      'Control' classes received no MCQs. When presented with a neuroscience quiz based
      on workshop content at the end of the workshop, pupils in the 'Risk' classes
      exhibited significantly greater recall of information one week later. Quiz scores
      were higher than scores from the day of the workshop which suggested pupils may
      have discussed the workshop content outside of the classroom, thereby increasing
      knowledge over and above what was learned during the workshop. This is supported
      by feedback from pupils in 'Risk' classes which indicated that 'Risk' workshops
      were more interesting than 'No risk' and 'Control' workshops. These data suggest
      that there is a role for risk in the classroom but further investigations are
      required to elucidate the causal mechanisms of improved retention of information.

PMID- 25072800
TI  - Efferent intestinal lymph protein responses in nematode-resistant, -resilient and
      -susceptible lambs under challenge with Trichostrongylus colubriformis.
AB  - The mechanisms underlying resistance to challenge by gastrointestinal nematode
      parasites in sheep are complex. Using DIGE, we profiled ovine lymph proteins in
      lambs with host resistance (R), resilience (Ri) or susceptibility (S) to a daily
      trickle challenge with the nematode Trichostrongylus colubriformis. Efferent
      intestinal lymph was collected prior to infection (day 1) and on days 5 and 10
      post-infection. Eight proteins identified by LC-MS/MS, showed differences
      relating to host genotype. Of these, Serpin A3-3 and Serpin A3-7 have not been
      reported previously in the lymph proteome. Three acute phase proteins showed
      significant differences relating to interactions between breeding line and
      parasite challenge, including complement C3beta, C3alpha and haptoglobin (Hp)
      beta. In the R lambs C3alpha was significantly up regulated (P<0.05) on day 10,
      while in the Ri lambs Hp beta was significantly down regulated (P<0.05). In the S
      lambs, levels of C3beta were up regulated and levels of Hp beta down regulated
      (both P<0.05) on day 10. Hence we demonstrate that acute phase inflammation
      proteins contribute to differences in the innate immune response of sheep to
      challenge by T. colubriformis. The findings may lead to the development of new
      approaches to combat nematode infestations in sheep production systems.
      BIOLOGICAL SIGNIFICANCE: Breeding lines of sheep with resistance (R), resilience
      (Ri) or susceptibility (S) to nematode infections provide an experimental model
      to examine the biological mechanisms underlying the ability of some sheep to
      expel worms and remain healthy without the use of an anthelmintic. Using
      proteomics we identified differences in the expression of acute phase lymph
      proteins in the R, Ri and S lambs. The results will assist the development of
      alternative control strategies to manage nematode infections in livestock.

PMID- 25072801
TI  - Local Treatment of Osteoporotic Sheep Vertebral Body With Calcium Sulfate for
      Decreasing the Potential Fracture Risk: Microstructural and Biomechanical
      Evaluations.
AB  - STUDY DESIGN: In this study, calcium sulfate (CS) was injected through pedicle
      into the osteoporotic vertebral body in vivo in sheep, and micro-computed
      tomography analysis, histologic observation, and biomechanical test were
      performed. OBJECTIVE: To investigate the improvement on microstructure and
      biomechanical performance of lumbar vertebrae augmented with CS in osteoporotic
      sheep. SUMMARY OF BACKGROUND DATA: The present treatments for osteoporosis relies
      on systemic medications intended to increase the bone mineral density (BMD).
      Although effective, these time-consuming medications provide little protection
      from fracture in the "early period" after initiation of therapy. In this regard,
      the strategy of local treatment is to target specific areas of the skeletal
      system that are prone to osteoporotic fractures. However, there is little or no
      research focused on local treatment of osteoporotic vertebrae with CS. METHODS:
      Eight female sheep were induced to osteoporosis with bilateral ovariectomy and
      methylprednisolone administration for 12 months. After successful establishment
      of an osteoporotic model, lumbar vertebrae (L1-L4) in every sheep were randomly
      divided into 2 groups: CS group and control group (2 vertebrae in each group in
      every sheep). CS was injected into the vertebral body transpedicularly in the CS
      group and no treatments were performed in the control group. Three months later,
      all sheep were killed and all L1-L4 vertebrae were harvested. Thereafter,
      microstructure and biomechanical performance of the cancellous bone of the
      vertebral body were assessed through micro-computed tomography analysis,
      histologic observation, and biomechanical test, respectively. RESULTS: After a 12
      month induction with ovariectomy and methylprednisolone administration, the mean
      BMD of the sheep lumbar vertebrae significantly decreased (>25%) compared with
      the value before induction, which demonstrated successful establishment of
      osteoporosis. Three months after injection of CS, CS was completely degraded
      without any remains in bone tissue and the quality of bone tissue (amount and
      density of the bone tissue) in the CS group was significantly higher than that in
      the control group. The ultimate load, stiffness, and energy absorption in the CS
      group were all significantly higher than those in the control group. CONCLUSIONS:
      The preliminary data suggest that local injection of CS can significantly improve
      the amount, density, and biomechanical performance of the bone trabeculae in
      osteoporotic vertebra. The local injection of CS could also be used as a new
      method to improve the physical microstructure and augment the mechanical
      properties in "high-risk" vertebral bodies, decreasing the potential fracture
      risk of patients with osteoporosis. The strict inclusion and exclusion criteria
      should be performed before treatment.

PMID- 25072802
TI  - The first stereoselective total synthesis of neosemburin and isoneosemburin.
AB  - The Claisen rearrangement of sugar derived allyl vinyl ether, Wittig olefination
      and intramolecular acetalization reactions were used as key steps in the first
      stereoselective total synthesis of neosemburin and isoneosemburin through the
      formation of a 3-C-branched sugar precursor as a key intermediate. 

PMID- 25072803
TI  - Ultranarrow band absorbers based on surface lattice resonances in nanostructured
      metal surfaces.
AB  - Nanostructured metals have received a significant amount of attention in recent
      years due to their exciting plasmonic and photonic properties enabling strong
      field localization, light concentration, and strong absorption and scattering at
      their resonance frequencies. Resonant plasmonic and metamaterial absorbers are of
      particular interest for applications in a wide variety of technologies including
      photothermal therapy, thermophotovoltaics, heat-assisted magnetic recording, hot
      electron collection, and biosensing. However, it is rather challenging to realize
      ultranarrow absorption bands using plasmonic materials due to large optical
      losses in metals that decrease the quality factor of optical resonators. Here, we
      theoretically and experimentally demonstrate an ultranarrow band absorber based
      on the surface lattice resonances (SLRs) in periodic nanowire and nanoring arrays
      on optically thick, reflecting metallic films. In experiments, we observed
      ultranarrow band resonant absorption peaks with a bandwidth of 12 nm and
      absorption amplitude exceeding 90% at visible frequencies. We demonstrate that
      the resonance absorption wavelength, amplitude of the absorption peak, and the
      bandwidth can be controlled by tuning the periodicity and the thickness of
      nanoring and nanowire arrays. Unlike conventional plasmonic absorbers utilizing
      common metal-insulator-metal stacks, our narrow band absorber consists solely of
      metals, facilitating stronger optical interaction between the SLR of periodic
      nanostructures and the highly reflective film. Moreover, by introducing asymmetry
      to the nanoring/nanowire hybrid system, we observe the spectral evolution of
      resonance splitting enabled by strong coupling between two individual SLRs
      arising from nanoring and nanowire arrays. Designing such all-metallic
      nanostructure arrays is a promising route for achieving ultranarrow band
      absorbers which can be used as absorption filters, narrow band thermal emitters
      in thermophotovoltaics, and plasmonic biosensors.

PMID- 25072804
TI  - Large left ventricular metastasis in patient with liposarcoma.
AB  - : Metastases to the heart and pericardium are rare. We present a 44-year-old male
      with pleural dedifferentiated liposarcoma and multiple metastases, with no
      previous cardiological history and/or cardiac symptoms. A transthoracic
      echocardiogram during the advanced stage of disease showed a lobulated, large and
      mobile mass, with homogeneous echogenicity, attached to the basal posterior wall
      of the left ventricle via a broad base and with intracavitary growth. This mass
      extends to inferolateral and inferoseptal wall of the left ventricle.

PMID- 25072805
TI  - Guanidyl-functionalized graphene as a bifunctional adsorbent for selective
      enrichment of phosphopeptides.
AB  - Guanidyl-functionalized graphene (GFG) was designed and synthesized. By simple
      modulation of the loading buffer this novel bifunctional adsorbent provides two
      enriching functions, one for global phosphopeptides, and the other for
      multiphosphopeptides with consecutive phosphorylated residues. GFG provides a
      promising perspective for consecutive phosphorylated peptide enrichment in
      phosphor-proteomic research and related biological process studies. 

PMID- 25072806
TI  - A novel "salvage" indication to intestinal derotation procedure: reconstruction
      after duodenopancreatectomy.
AB  - PATIENT: Male, 77. FINAL DIAGNOSIS: Pancreatic tumor. SYMPTOMS: Jaundice.
      MEDICATION: -. CLINICAL PROCEDURE: Intestinal derotation procedure. SPECIALTY:
      General surgery. OBJECTIVE: Rare disease. BACKGROUND: The purpose of the present
      paper is to stress the relevance for surgeons of being familiar with the
      procedure of intestinal derotation. This procedure is usually ignored by atlases
      of surgical technique and only few dedicated papers have been published since its
      first descriptions both in the U.S. and Europe more than 50 yrs ago. CASE REPORT:
      The occasion for this message has been provided by a recent application of this
      procedure, which has also provided a brand new indication to it. In the case
      which is reported in the paper the reconstruction, after the resection phase of
      Whipple procedure, appeared impossible. As a matter of fact, a lipomatosis of the
      jejunal mesentery reaching up the vasa recta made impossible to raise up the
      jejunum in order to perform anastomoses with the remaining pancreas and the bile
      duct. After a minute in which we felt lost, intestinal derotation solved the
      problem. CONCLUSIONS: In conclusion, intestinal derotation represents a valuable
      technical tool, which in very selected cases may be helpful in solving otherwise
      insoluble surgical problems. Therefore, it seems to be a necessary part of the
      armamentarium of any good surgeon.

PMID- 25072807
TI  - Molecular junctions: can pulling influence optical controllability?
AB  - We suggest the combination of single molecule pulling and optical control as a
      way to enhance control over the electron transport characteristics of a molecular
      junction. We demonstrate using a model junction consisting of biphenyl-dithiol
      coupled to gold contacts. The junction is pulled while optically manipulating the
      dihedral angle between the two rings. Quantum dynamics simulations show that
      molecular pulling enhances the degree of control over the dihedral angle and
      hence over the transport properties. 

PMID- 25072808
TI  - Manifestation of magnetic quantum fluctuations in the dielectric properties of a
      multiferroic.
AB  - Insulating magnets can display novel signatures of quantum fluctuations as
      similar to the case of metallic magnets. However, their weak spin-lattice
      coupling has made such observations challenging. Here we find that
      antiferromagnetic (AF) quantum fluctuations manifest in the dielectric properties
      of multiferroic Ba2CoGe2O7, where a ferroelectric polarization develops
      concomitant to an AF ordering. Upon application of a magnetic field (H),
      dielectric constant shows a characteristic power-law dependence near absolute
      zero temperature and close to the critical field Hc=37.1 T due to enhanced AF
      quantum fluctuations. When H>Hc, the dielectric constant shows the temperature
      dependent anomalies that reflect a crossover from a field-tuned quantum critical
      to a gapped spin-polarized state. We uncover theoretically that a linear relation
      between AF susceptibility and dielectric constant stems from the generic
      magnetoelectric coupling and directly explains the experimental findings, opening
      a new pathway for studying quantum criticality in condensed matter. 

PMID- 25072809
TI  - Traumatic rupture of deep neck structures in hanging: two case reports.
AB  - Injuries to the neck structures are various in case of hanging. Soft tissue
      lesions generally consist in sternocleidomastoid and subhyoid muscle hemorrhages.
      Traumatic ruptures of deep neck structures are rare. We report 2 cases of partial
      and complete ruptures of sternocleidomastoid muscles after suicidal hanging. Both
      were typical and complete hanging. In 1 case, muscle laceration was associated
      with common carotid rupture on the same side. Hemorrhage at the rupture site was
      only found at the microscopic level. Such injuries may result from the ligature's
      compression and depend on duration of suspension. Heavy body weight, rigid rope
      material, and fall after a jump may promote their occurrence. 

PMID- 25072810
TI  - Postmortem findings in bone cement implantation syndrome-related deaths.
AB  - Several mechanisms have been postulated as potentially involved in life
      threatening complications during cemented surgery. In this study, we evaluated
      the role of anaphylaxis and pulmonary fat embolism in the pathophysiology of bone
      cement implantation syndrome in a series of fatal cases that underwent
      medicolegal investigations. Postmortem findings in these cases were compared with
      those obtained from individuals who died after other injuries and/or
      interventions and in which activated mast cells and pulmonary fat embolism were
      involved in the pathogenesis of death. Fifty subjects were selected including 6
      individuals who had undergone cemented total hip arthroplasty and died
      intraoperatively, 32 subjects who died shortly after being involved in traffic
      accidents, 8 individuals who died shortly after the injection of contrast
      material, and 4 subjects who had undergone orthopedic surgery and died
      postoperatively. Massive pulmonary fat embolism was determined to be the cause of
      death in all the 6 subjects who died intraoperatively as well as the main cause
      of death in traffic-road victims with rapid respiratory function deterioration.
      Mast cell activation was identified exclusively in the group of subjects who died
      shortly after contrast material administration. Massive pulmonary fat embolism
      appears to be the most important factor responsible for severe cardiorespiratory
      function deterioration during cemented arthroplasty. Cardiac comorbidities can
      also significantly influence the severity of intraoperative complications, thus
      corroborating the hypothesis of a multifactorial model in the pathogenesis of
      bone cement implantation syndrome. 

PMID- 25072811
TI  - Fatal head injuries in children under the age of 5 years in Pretoria.
AB  - The incidence of fatal injuries in children has been reported to be highest among
      children aged 1 to 4 years. Major causes of head injury include road traffic
      accidents, falls, and intentional or inflicted injury (such as nonaccidental
      injury syndrome). This study reviewed the profile of children (under 5 years of
      age) who had been admitted to a large urban medicolegal mortuary (in Pretoria,
      the capital city of South Africa), after having suffered fatal head injuries.
      This study was conducted over a 5-year period (from January 2004 through December
      2008), and a total of 107 cases were identified for inclusion. These cases
      constituted nearly a fifth of admissions in this age group. The male-to-female
      ratio was 56%:44%, and the peak age of injury was less than 1 year. Most head
      injuries were sustained in road traffic accidents (70%) followed by falls (10%)
      and other types of blunt force injuries (9%). Only 1 case of nonaccidental injury
      syndrome (child abuse) was found. The great majority of deaths were deemed to
      have been accidental in nature (91%) with 6 (6%) homicides. Urgent review
      pertaining to the use of child restraint devices and the safety of pedestrians is
      required, and the institution of childhood injury registers could aid in reducing
      childhood fatalities in South Africa. 

PMID- 25072812
TI  - Three-dimensional printing of freeform helical microstructures: a review.
AB  - Three-dimensional (3D) printing is a fabrication method that enables creation of
      structures from digital models. Among the different structures fabricated by 3D
      printing methods, helical microstructures attracted the attention of the
      researchers due to their potential in different fields such as MEMS, lab-on-a
      chip systems, microelectronics and telecommunications. Here we review different
      types of 3D printing methods capable of fabricating 3D freeform helical
      microstructures. The techniques including two more common microfabrication
      methods (i.e., focused ion beam chemical vapour deposition and
      microstereolithography) and also five methods based on computer-controlled
      robotic direct deposition of ink filament (i.e., fused deposition modeling,
      meniscus-confined electrodeposition, conformal printing on a rotating mandrel, UV
      assisted and solvent-cast 3D printings) and their advantages and disadvantages
      regarding their utilization for the fabrication of helical microstructures are
      discussed. Focused ion beam chemical vapour deposition and microstereolithography
      techniques enable the fabrication of very precise shapes with a resolution down
      to ~100 nm. However, these techniques may have material constraints (e.g., low
      viscosity) and/or may need special process conditions (e.g., vacuum chamber) and
      expensive equipment. The five other techniques based on robotic extrusion of
      materials through a nozzle are relatively cost-effective, however show lower
      resolution and less precise features. The popular fused deposition modeling
      method offers a wide variety of printable materials but the helical
      microstructures manufactured featured a less precise geometry compared to the
      other printing methods discussed in this review. The UV-assisted and the solvent
      cast 3D printing methods both demonstrated high performance for the printing of
      3D freeform structures such as the helix shape. However, the compatible materials
      used in these methods were limited to UV-curable polymers and polylactic acid
      (PLA), respectively. Meniscus-confined electrodeposition is a flexible, low cost
      technique that is capable of fabricating 3D structures both in nano- and
      microscales including freeform helical microstructures (down to few microns)
      under room conditions using metals. However, the metals suitable for this
      technique are limited to those that can be electrochemically deposited with the
      use of an electrolyte solution. The highest precision on the helix geometry was
      achieved using the conformal printing on a rotating mandrel. This method offers
      the lowest shape deformation after printing but requires more tools (e.g.,
      mandrel, motor) and the printed structure must be separated from the mandrel.
      Helical microstructures made of multifunctional materials (e.g., carbon nanotube
      nanocomposites, metallic coated polymer template) were used in different
      technological applications such as strain/load sensors, cell separators and micro
      antennas. These innovative 3D microsystems exploiting the unique helix shape
      demonstrated their potential for better performance and more compact
      microsystems. 

PMID- 25072813
TI  - Rogue sperm indicate sexually antagonistic coevolution in nematodes.
AB  - Intense reproductive competition often continues long after animals finish
      mating. In many species, sperm from one male compete with those from others to
      find and fertilize oocytes. Since this competition occurs inside the female
      reproductive tract, she often influences the outcome through physical or chemical
      factors, leading to cryptic female choice. Finally, traits that help males
      compete with each other are sometimes harmful to females, and female
      countermeasures may thwart the interests of males, which can lead to an arms race
      between the sexes known as sexually antagonistic coevolution. New studies from
      Caenorhabditis nematodes suggest that males compete with each other by producing
      sperm that migrate aggressively and that these sperm may be more likely to win
      access to oocytes. However, one byproduct of this competition appears to be an
      increased probability that these sperm will go astray, invading the ovary,
      prematurely activating oocytes, and sometimes crossing basement membranes and
      leaving the gonad altogether. These harmful effects are sometimes observed in
      crosses between animals of the same species but are most easily detected in
      interspecies crosses, leading to dramatically lowered fitness, presumably because
      the competitiveness of the sperm and the associated female countermeasures are
      not precisely matched. This mismatch is most obvious in crosses involving
      individuals from androdioecious species (which have both hermaphrodites and
      males), as predicted by the lower levels of sperm competition these species
      experience. These results suggest a striking example of sexually antagonistic
      coevolution and dramatically expand the value of nematodes as a laboratory system
      for studying postcopulatory interactions. 

PMID- 25072815
TI  - ChemDoodle 6.0.
AB  - ChemDoodle 6.0 is an advanced software suite for drawing chemical structure
      diagrams. The program's capabilities extend far beyond mere structures, however,
      including the ability to calculate NMR spectra, generate IUPAC names and line
      notations for structures, manipulate structures imported from the Internet,
      interpret and interconvert files generated by other chemical drawing software
      programs, illustrate glassware and equipment setups, and draw TLC plates. This
      latest version supports full round-trip editing, so that structures produced with
      the program can be used in standard office software and reimported into
      ChemDoodle if modifications are needed. These features and more are included in
      the basic package, which is very affordable. 

PMID- 25072814
TI  - NOA1, a novel ClpXP substrate, takes an unexpected nuclear detour prior to
      mitochondrial import.
AB  - The mitochondrial matrix GTPase NOA1 is a nuclear encoded protein, essential for
      mitochondrial protein synthesis, oxidative phosphorylation and ATP production.
      Here, we demonstrate that newly translated NOA1 protein is imported into the
      nucleus, where it localizes to the nucleolus and interacts with UBF1 before
      nuclear export and import into mitochondria. Mutation of the nuclear localization
      signal (NLS) prevented both nuclear and mitochondrial import while deletion of
      the N-terminal mitochondrial targeting sequence (MTS) or the C-terminal RNA
      binding domain of NOA1 impaired mitochondrial import. Absence of the MTS resulted
      in accumulation of NOA1 in the nucleus and increased caspase-dependent apoptosis.
      We also found that export of NOA1 from the nucleus requires a leptomycin-B
      sensitive, Crm1-dependent nuclear export signal (NES). Finally, we show that NOA1
      is a new substrate of the mitochondrial matrix protease complex ClpXP. Our
      results uncovered an unexpected, mandatory detour of NOA1 through the nucleolus
      before uptake into mitochondria. We propose that nucleo-mitochondrial
      translocation of proteins is more widespread than previously anticipated
      providing additional means to control protein bioavailability as well as cellular
      communication between both compartments. 

PMID- 25072817
TI  - Structural and community-level interventions for increasing condom use to prevent
      the transmission of HIV and other sexually transmitted infections.
AB  - BACKGROUND: Community interventions to promote condom use are considered to be a
      valuable tool to reduce the transmission of human immunodeficiency virus (HIV)
      and other sexually transmitted infections (STIs). In particular, special emphasis
      has been placed on implementing such interventions through structural changes, a
      concept that implies public health actions that aim to improve society's health
      through modifications in the context wherein health-related risk behavior takes
      place. This strategy attempts to increase condom use and in turn lower the
      transmission of HIV and other STIs. OBJECTIVES: To assess the effects of
      structural and community-level interventions for increasing condom use in both
      general and high-risk populations to reduce the incidence of HIV and STI
      transmission by comparing alternative strategies, or by assessing the effects of
      a strategy compared with a control. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, from 2007,
      Issue 1), as well as MEDLINE, EMBASE, AEGIS and ClinicalTrials.gov, from January
      1980 to April 2014. We also handsearched proceedings of international acquired
      immunodeficiency syndrome (AIDS) conferences, as well as major behavioral studies
      conferences focusing on HIV/AIDS and STIs. SELECTION CRITERIA: Randomized control
      trials (RCTs) featuring all of the following.1. Community interventions
      ('community' defined as a geographical entity, such as cities, counties,
      villages).2. One or more structural interventions whose objective was to promote
      condom use. These type of interventions can be defined as those actions improving
      accessibility, availability and acceptability of any given health
      program/technology.3. Trials that confirmed biological outcomes using laboratory
      testing. DATA COLLECTION AND ANALYSIS: Two authors independently screened and
      selected relevant studies, and conducted further risk of bias assessment. We
      assessed the effect of treatment by pooling trials with comparable
      characteristics and quantified its effect size using risk ratio. The effect of
      clustering at the community level was addressed through intra-cluster correlation
      coefficients (ICCs), and sensitivity analysis was carried out with different
      design effect values. MAIN RESULTS: We included nine trials (plus one study that
      was a subanalysis) for quantitative assessment. The studies were conducted in
      Tanzania, Zimbabwe, South Africa, Uganda, Kenya, Peru, China, India and Russia,
      comprising 75,891 participants, mostly including the general population (not the
      high-risk population). The main intervention was condom promotion, or
      distribution, or both. In general, control groups did not receive any active
      intervention. The main risk of bias was incomplete outcome data.In the meta
      analysis, there was no clear evidence that the intervention had an effect on
      either HIV seroprevalence or HIV seroincidence when compared to controls: HIV
      incidence (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.69 to 1.19) and
      HIV prevalence (RR 1.02, 95% CI 0.79 to 1.32). The estimated effect of the
      intervention on other outcomes was similarly uncertain: Herpes simplex virus 2
      (HSV-2) incidence (RR 0.76, 95% CI 0.55 to 1.04); HSV-2 prevalence (RR 1.01, 95%
      CI 0.85 to 1.20); syphilis prevalence (RR 0.91, 95% CI 0.71 to 1.17); gonorrhoea
      prevalence (RR 1.16, 95% CI 0.67 to 2.02); chlamydia prevalence (RR 0.94, 95% CI
      0.75 to 1.18); and trichomonas prevalence (RR 1.00, 95% CI 0.77 to 1.30).
      Reported condom use increased in the experimental arm (RR 1.20, 95% CI 1.03 to
      1.40). In the intervention groups, the number of people reporting two or more
      sexual partners in the past year did not show a clear decrease when compared with
      control groups (RR 0.90, 95% CI 0.78 to 1.04), but knowledge about HIV and other
      STIs improved (RR 1.15, 95% CI 1.04 to 1.28, and RR 1.23, 95% CI 1.07 to 1.41,
      respectively). The quality of the evidence was deemed to be moderate for nearly
      all key outcomes. AUTHORS' CONCLUSIONS: There is no clear evidence that
      structural interventions at the community level to increase condom use prevent
      the transmission of HIV and other STIs. However, this conclusion should be
      interpreted with caution since our results have wide confidence intervals and the
      results for prevalence may be affected by attrition bias. In addition, it was not
      possible to find RCTs in which extended changes to policies were conducted and
      the results only apply to general populations in developing nations, particularly
      to Sub-Saharan Africa, a region which in turn is widely diverse.

PMID- 25072818
TI  - In vivo striatal measurement of hydroxytyrosol, and its metabolite (homovanillic
      alcohol), compared with its derivative nitrohydroxytyrosol.
AB  - Phenolic compounds were measured by in vivo brain microdialysis in rat striatum.
      Basal extracellular levels of hydroxytyrosol, homovanillic alcohol and nitro
      hydroxytyrosol were not detectable by HPLC with electrochemical detection.
      However, systemic administration of hydroxytyrosol (20 and 40mg/kg, i.p.) showed
      a clear increase in the extracellular level of this compound. This increase was
      accompanied by an increase in the extracellular level of homovanillic alcohol, a
      metabolite of hydroxytyrosol formed by catechol-O-methyltransferase activity.
      Perfusion of hydroxytyrosol (20MUM) through the microdialysis cannula also
      produced an increase in the extracellular level of homovanillic alcohol. Systemic
      administration of nitro-hydroxytyrosol (20 and 40mg/kg, i.p.) produced a small
      increase in the extracellular level of this compound. Our data show that
      hydroxytyrosol is a more brain penetrant phenolic compound than nitro
      hydroxytyrosol. Accordingly, there is high cerebral metabolism of hydroxytyrosol
      to produce homovanillic alcohol by catechol-O-methyltransferase activity, that is
      saturated at the higher administered dose of hydroxytyrosol. 

PMID- 25072816
TI  - BNP but Not s-cTnln is associated with cardioembolic aetiology and predicts short
      and long term prognosis after cerebrovascular events.
AB  - BACKGROUND: We analyzed the prognostic value of b-type natriuretic peptide (BNP)
      and sensitive cardiac Troponin (s-cTnI) in patients with ischemic stroke or
      transient ischemic attack (TIA) and their significance in predicting stroke
      aetiology. METHODS: In a prospectively enrolled cohort we measured BNP and s-cTnI
      levels upon admission. Primary endpoints were mortality, unfavorable functional
      outcome and stroke recurrence after 90 days and after 12 months. Secondary
      endpoint was cardioembolic aetiology. RESULTS: In 441 patients BNP but not s-cTnI
      remained an independent predictor for death with an adjusted HR of 1.2 (95% CI
      1.1-1.4) after 90 days and 1.2 (95% CI 1.0-1.3) after one year. The comparison of
      the Area under Receiver Operating Characteristic (AUROC) of model A (age, NIHSS)
      and model B (age, NIHSS, BNP) showed an improvement in the prediction of
      mortality (0.85 (95% CI 0.79-0.90) vs. 0.86 (95% CI 0.81-0.92), Log Rank p =
      0.004). Furthermore the category free net reclassification improvement (cfNRI)
      when adding BNP to the multivariate model was 57.5%, p<0.0001. For the prediction
      of functional outcome or stroke recurrence both markers provided no incremental
      value. Adding BNP to a model including age, atrial fibrillation and heart failure
      lead to a higher discriminatory accuracy for identification of cardioembolic
      stroke than the model without BNP (AUC 0.75 (95% CI 0.70-0.80) vs. AUC 0.79, (95%
      CI 0.75-0.84), p = 0.008). CONCLUSION: BNP is an independent prognostic maker for
      overall mortality in patients with ischemic stroke or TIA and may improve the
      diagnostic accuracy to identify cardioembolic aetiology. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00390962.

PMID- 25072820
TI  - Social network analysis predicts health behaviours and self-reported health in
      African villages.
AB  - The provision of healthcare in rural African communities is a highly complex and
      largely unsolved problem. Two main difficulties are the identification of
      individuals that are most likely affected by disease and the prediction of
      responses to health interventions. Social networks have been shown to capture
      health outcomes in a variety of contexts. Yet, it is an open question as to what
      extent social network analysis can identify and distinguish among households that
      are most likely to report poor health and those most likely to respond to
      positive behavioural influences. We use data from seven highly remote, post
      conflict villages in Liberia and compare two prominent network measures: in
      degree and betweenness. We define in-degree as the frequency in which members
      from one household are named by another household as a friends. Betweenness is
      defined as the proportion of shortest friendship paths between any two households
      in a network that traverses a particular household. We find that in-degree
      explains the number of ill family members, whereas betweenness explains
      engagement in preventative health. In-degree and betweenness independently
      explained self-reported health and behaviour, respectively. Further, we find that
      betweenness predicts susceptibility to, instead of influence over, good health
      behaviours. The results suggest that targeting households based on network
      measures rather than health status may be effective for promoting the uptake of
      health interventions in rural poor villages. 

PMID- 25072821
TI  - Lead levels in the breast milk of nursing andean mothers living in a lead
      contaminated environment.
AB  - Concentrations of lead (Pb) in breast milk (PbM) and blood (PbB) were measured in
      a current cohort of lactating mothers living in Andean communities where women of
      childbearing age engage in the occupational use of Pb, and compared to results
      obtained in earlier studies. Mean PbM concentration in the current group of
      breastfeeding mothers tested in 2012/2013 was 3.73 MUg/L (SD: 7.3; range: 0.049
      28.04), and significantly lower than the 9.83 MUg/L (SD: 12.75; range: 0.2-49)
      previously observed in breastfeeding mothers in the study area from 1999 to 2007.
      Breastfeeding women in the current cohort showed an average PbM/PbB ratio of
      3.6%, which is in agreement with other studies. The mean PbB level obtained for
      the current cohort was 7.8 MUg/dl (SD: 5.2; range: 1.4-21), and significantly
      lower than the mean PbB level of 20.8 MUg/dl (SD: 16.4; range: 4-73) obtained for
      the comparison group of breastfeeding mothers tested between 1999 and 2007. A
      correlation of .687 between paired PbM and maternal PbB was found, indicating
      that maternal PbB level is a significant predictor of PbM. Current PbM levels
      remain higher than international averages, but indicate that maternal Pb exposure
      has declined over time in the environmentally Pb-contaminated study area. The
      current reduction in Pb in milk and blood of breastfeeding mothers may be due to
      adherence to a Pb-exposure education and prevention program initiated by the
      authors in the study area years earlier, as well as recent improvements in local
      health care delivery. 

PMID- 25072822
TI  - Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for
      cardiovascular risk.
AB  - Methylmercury (MeHg) has been associated with increased risk for cardiovascular
      disease in some but not all epidemiology studies. These inconsistent results may
      stem from the fact that exposure typically occurs in the context of fish
      consumption, which is also associated with cardioprotective factors such as omega
      3 fatty acids. Mechanistic information may help to understand whether MeHg
      represents a risk to cardiovascular health. MeHg is a pro-oxidant that
      inactivates protein sulfhydryls. These biochemical effects may diminish critical
      antioxidant defense mechanism(s) involved in protecting against atherosclerosis.
      One such defense mechanism is paraoxonase-1 (PON1), an enzyme present on high
      density lipoproteins and that prevents the oxidation of blood lipids and their
      deposition in vascular endothelium. PON1 is potentially useful as a clinical
      biomarker of cardiovascular risk, as well as a critical enzyme in the
      detoxification of certain organophosphate oxons. MeHg and other metals are known
      to inhibit PON1 activity in vitro. MeHg is associated with lowered serum PON1
      activity in a fish-eating population. The implications of lowering PON1 are
      evaluated by predicting the shift in PON1 population distribution induced by
      various doses of MeHg. An MeHg dose of 0.3 MUg/kg/d is estimated to decrease the
      population average PON1 level by 6.1% and to increase population risk of acute
      cardiovascular events by 9.7%. This evaluation provides a plausible mechanism for
      MeHg-induced cardiovascular risk and suggests means to quantify the risk. This
      case study exemplifies the use of upstream disease biomarkers to evaluate the
      additive effect of chemical toxicity with background disease processes in
      assessing human risk. 

PMID- 25072823
TI  - Early and delayed effects of naturally occurring asbestos on serum biomarkers of
      inflammation and metabolism.
AB  - Studies recently showed that intratracheal (IT) instillation of Libby amphibole
      (LA) increases circulating acute-phase proteins (APP; alpha-2 macroglobulin, A2M;
      and alpha-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and
      lipocalin) in rats. In this study, objectives were to (1) compare changes in
      biomarkers of rats after instillation of different naturally occurring asbestos
      (NOA) minerals including LA, Sumas Mountain chrysotile (SM), El Dorado Hills
      tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON), and (2)
      examine biomarkers after subchronic LA or amosite inhalation exposure. Rat
      respirable fractions (aerodynamic diameter approximately 2.5 MUm) prepared by
      water elutriation were delivered via a single IT instillation at doses of 0, 0.5,
      and 1.5 mg/rat in male F344 rats. Nose-only inhalation exposures were performed
      at 0, 1, 3.3, and 10 mg/m(3) for LA and at 3.3 mg /m(3) for amosite, 6h/d, 5 d/wk
      for 13 wk. Inflammation, metabolic syndrome, and cancer biomarkers were analyzed
      in the serum for up to 18 mo. IT instillation of some asbestos materials
      significantly increased serum AGP and A2M but to a varying degree (SM = LA > ON =
      ED). Numerical increases in interleukin (IL)-6 and osteopontin occurred in rats
      instilled with SM. SM and ED also elevated leptin and insulin at 15 mo,
      suggesting potential metabolic effects. LA inhalation tended to raise A2M at d 1
      but not cytokines. Serum mesothelin appeared to elevate after 18 mo of LA
      inhalation. These results suggest that the lung injury induced by high levels of
      asbestos materials may be associated with systemic inflammatory changes and
      predisposition to insulin resistance. 

PMID- 25072824
TI  - The course of toxicity in the pregnant mouse after exposure to the cyanobacterial
      toxin cylindrospermopsin: clinical effects, serum chemistries, hematology, and
      histopathology.
AB  - Cylindrospermopsin (CYN) is a toxin produced by a variety of fresh-water
      cyanobacterial species worldwide and induces significant adverse effects in both
      livestock and humans. This study investigated the course of CYN-induced toxicity
      in pregnant mice exposed daily during either the period of major organogenesis
      (gestation days [GD] 8-12) or fetal growth (GD13-17). Endpoints include clinical
      signs of toxicity, serum analyses to evaluate hepatic and renal function,
      histopathology of liver and kidney, and hematology. Study animals were
      administered 50 MUg/kg CYN once daily by ip route and euthanized 24 h after 1, 2,
      3, 4, or 5 consecutive doses, or 6 or 13 d after the dosing period. The course of
      the CYN-induced effects was determined at all euthanasia times for the endpoints
      just outlined. Results indicated that CYN is a toxin, producing lethality in dams
      during the early part of gestation, significant weight loss, and bleeding in the
      gastrointestinal tract, tail tip, and peri-orbital tissues. Effects also included
      alterations in serum markers for liver function, histopathological changes in
      liver and kidney tissues, electrolyte abnormalities, leukocytosis, and
      posttreatment thrombocytopenia and reticulocytosis. The onset of symptoms was
      rapid, producing reductions in weight gain in GD8-12 animals, bleeding in the
      vaginal area in GD13-17 animals, and significant increases in sorbitol
      dehydrogenase (SDH) in both groups after a single dose. Although the GD8-12 dams
      displayed a 50% lethality, in GD13-17 animals only a single death occurred.
      Alterations seen in hepatic and renal function or histopathology do not appear to
      be of sufficient severity to produce death. Evidence indicates that bleeding may
      play a critical role in the onset of symptoms and eventually, in the observed
      lethality. 

PMID- 25072825
TI  - Recovery of vascular function after exposure to a single bout of segmental
      vibration.
AB  - Work rotation schedules may be used to reduce the negative effects of vibration
      on vascular function. This study determined how long it takes vascular function
      to recover after a single exposure to vibration in rats (125 Hz, acceleration 5
      g). The responsiveness of rat-tail arteries to the vasoconstricting factor
      UK14304, an alpha2C-adrenoreceptor agonist, and the vasodilating factor
      acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a
      single bout of vibration. Vasoconstriction induced by UK14304 returned to control
      levels after 1 d of recovery. However, re-dilation induced by ACh did not return
      to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged
      effects on peripheral vascular function, and altered vascular responses to a
      subsequent exposure. To optimize the positive results of work rotation schedules,
      it is suggested that studies assessing recovery of vascular function after
      exposure to a single bout of vibration be performed in humans.

PMID- 25072827
TI  - Spin polarons in EuO layers: a quantum computational study.
AB  - Magnetic semiconductors are highly promising materials for spintronics. Among
      them europium(ii) oxide makes a unique working host material due to a remarkable
      combination of magnetic and transport properties. Its electronic structure and
      various properties are often described in terms of spin polarons - local
      ferromagnetic clusters in the paramagnetic sea of Eu ions. This concept finds
      support in numerous experiments and theoretical studies but so far it has not
      emerged in quantum-chemical calculations of this material. Here we try to find
      evidence for the existence of these quasiparticles from local cluster
      calculations for different values of the total spin. Our calculations of EuO
      layers show that there are low-energy states consistent with quasi-two
      dimensional spin polarons as part of their electronic structure. The size of
      these quasiparticles (radius R ~ 0.5 nm and spin S ~ 38) doesn't change with the
      size of the cluster and is in good accord with experimental results. 

PMID- 25072828
TI  - Distribution of free-living amoebae in a treatment system of textile industrial
      wastewater.
AB  - Free-living amoebae have been found in soil, air and a variety of aquatic
      environments, but few studies have been conducted on industrial wastewater and
      none on wastewater from the textile industry. The aim of this study was to
      determine the presence and distribution of free-living amoebae in a biological
      treatment system that treats textile industrial wastewater. Samples were taken
      from input, aeration tank, sedimentation tank and output. Samples were
      centrifuged at 1200g for 15min, the sediment was seeded on non-nutritive agar
      with Enterobacter aerogenes (NNE) and the plates were incubated at 30 and 37
      degrees C. Free-living amoebae were present in all stages of the treatment
      system. The highest number of amoebic isolates was found in the aeration tank and
      no seasonal distribution was observed during the year. A total of 14 amoeba
      genera were isolated: Acanthamoeba, Echinamoeba, Korotnevella, Mayorella,
      Naegleria, Platyamoeba, Saccamoeba, Stachyamoeba, Thecamoeba, Vahlkampfia,
      Vannella, Vermamoeba, Vexillifera and Willaertia. The most frequently found
      amoebae were Acanthamoeba and Vermamoeba which were found in all treatment system
      stages. The constant presence and diversity of free-living amoebae in the
      treatment system were important findings due to the characteristics of the
      wastewater from the textile plant in terms of the residue content from colorants,
      fixers, carriers, surfactants, etc., used in fabric dyeing and finishing
      processes. The factors that determined the presence and distribution of amoebae
      in the activated sludge system were their capacity to form cysts, which allowed
      them to resist adverse conditions; food availability; an average temperature of
      27-33 degrees C; dissolved oxygen in average concentrations above 2mg/L, and pH
      in a range of 5.9-7.1. 

PMID- 25072829
TI  - Effect of Implant Diameter and Ridge Dimension on Stress Distribution in
      Mandibular First Molar Sites-A Photoelastic Study.
AB  - The long-term clinical success of a dental implant is dependent upon maintaining
      sufficient osseointegration to resist forces of occlusion. The purpose of this
      study was to investigate the effect of implant diameter on stress distribution
      around screw-type dental implants in mandibular first molar sites using
      photoelastic models. The design included models with different buccal-lingual
      dimension. Twelve composite photoelastic models were assembled using 2 different
      resins to simulate trabecular and cortical bone. Half of the models were
      fabricated with average dimensions for ridge width and the other half with
      narrower buccal-lingual dimensions. One internal connection implant (13 mm
      length) with either a standard (4 mm), wide (5 mm), or narrow (3.3 mm) diameter
      was embedded in the first molar position of each photoelastic model. Half the
      implants were tapered and the other half were straight. Full gold crowns in the
      shape of a mandibular first molar were fabricated and attached to the implants.
      Vertical and angled loads of 15 and 30 pounds were applied to specific points on
      the crown. Wide-diameter implants produced the least stress in all ridges while
      narrow-diameter implants generated the highest stress, especially in narrow
      ridges. It may be that the volume and quality of bone surrounding implants
      influences stress distribution with a greater ratio of cortical to trabecular
      bone, thus providing better support. Models with wide-diameter implants loaded
      axially had a more symmetrical stress distribution compared to standard and
      narrow diameter implants. A more asymmetrical stress pattern developed along the
      entire implant length with angled loads. Implant diameter and ridge width had
      considerable influence on stress distribution. Narrow-diameter implants produced
      more stress than wide diameter implants in all conditions tested. 

PMID- 25072830
TI  - Direct three-dimensional characterization and multiscale visualization of wheat
      straw deconstruction by white rot fungus.
AB  - Microbial degradation of lignocellulose for resource and energy recovery has
      received increasing interest. Despite its obvious importance, the mechanism
      behind the biodegradation, especially the changes of morphological structure and
      surface characteristics, has not been fully understood. Here, we used three
      dimensional (3D) characterization and multiscale visualization methods, in
      combination with chemical compositional analyses, to elucidate the degradation
      process of wheat straw by a white rot fungus, Phanerochaete chrysosporium. It was
      found that the fungal attack initiated from stomata. Lignin of the straw decayed
      in both size and quantity, and heterogeneity in the biodegradation was observed.
      After treatment with the fungus, the straw surface turned from hydrophobic to
      hydrophilic, and the adhesion of the straw surface increased in the fungal
      degradation. The morphology of the straw outer layer became heterogeneous and
      loose with the formation of many holes with various sizes. The wasp-tunnels-like
      structure of the collenchyma and parenchyma of the straw as well as the fungal
      hyphae interspersed inside the straw structure were clearly visualized in the 3D
      reconstruction structure. This work offers a new insight into the mechanism of
      lignocellulose biodegradation and demonstrates that multiscale visualization
      methods could be a useful tool to explore such complex processes. 

PMID- 25072831
TI  - Myopia in young adults is inversely related to an objective marker of ocular sun
      exposure: the Western Australian Raine cohort study.
AB  - PURPOSE: To determine the association between ocular sun exposure measured by
      conjunctival ultraviolet (UV) autofluorescence and myopic refractive error in
      young adults. DESIGN: Cross-sectional study. METHODS: setting: Population-based
      cohort in Western Australia. study population: Total of 1344 mostly white
      subjects aged 19-22 years in the Western Australian Pregnancy Cohort (Raine) Eye
      Health Study. observation procedures: Cycloplegic autorefraction, conjunctival
      ultraviolet autofluorescence photography, participant questionnaire. main outcome
      measures: Prevalence of myopic refractive error (spherical equivalent less than 
      0.50 diopters) and area of conjunctival ultraviolet autofluorescence in mm(2).
      RESULTS: There was an inverse relationship between myopic refractive error and
      ocular sun exposure, with more than double the prevalence of myopia in the lowest
      quartile of conjunctival autofluorescence than the highest quartile (33.0% vs
      15.6%). Median area of autofluorescence was significantly lower in myopic than in
      nonmyopic subjects (31.9 mm(2) vs 47.9 mm(2), P < .001). These differences
      remained significant after adjustment for age, sex, parental history of myopia,
      and subject level of education. The use of corrective lenses did not explain the
      lower conjunctival autofluorescence observed in myopic subjects. CONCLUSIONS: In
      this young adult population, myopic refractive error was inversely associated
      with objectively measured ocular sun exposure, even after adjustment for
      potential confounders. This further supports the inverse association between
      outdoor activity and myopia.

PMID- 25072832
TI  - Complications related to a cosmetic eye-whitening procedure.
AB  - PURPOSE: To report sight-threatening complications following extensive bulbar
      conjunctival resection and postoperative mitomycin C therapy for cosmetic eye
      whitening in the United States. DESIGN: Retrospective noncomparative case series.
      METHODS: Multicenter report of 9 patients referred for evaluation and management
      of complications following bilateral cosmetic eye whitening. RESULTS: Seventeen
      eyes of 9 patients underwent cosmetic eye-whitening performed between 2 and 48
      months prior to referral to one of the centers. Sixteen of the 17 eyes had
      persistent conjunctival epithelial defects, with 10 eyes requiring amniotic
      membrane grafting to facilitate re-epithelialization. Four eyes of 2 patients
      developed limbal stem cell compromise confirmed with in vivo confocal laser
      scanning microscopy. One patient developed infectious scleritis and diplopia
      resulting from Tenon capsule scarring. Another patient developed scleral
      necrosis, secondary infectious scleritis, and infectious endophthalmitis. This
      patient subsequently developed noninfectious scleritis that required 3-drug
      regimen immunosuppression. CONCLUSION: Severe adverse effects can occur after
      extensive cosmetic conjunctival resection followed by topical mitomycin C
      application. Patients and physicians should be aware of the potential sight
      threatening complications associated with this eye-whitening procedure.

PMID- 25072833
TI  - Audience preferences are predicted by temporal reliability of neural processing.
AB  - Naturalistic stimuli evoke highly reliable brain activity across viewers. Here we
      record neural activity from a group of naive individuals while viewing popular,
      previously-broadcast television content for which the broad audience response is
      characterized by social media activity and audience ratings. We find that the
      level of inter-subject correlation in the evoked encephalographic responses
      predicts the expressions of interest and preference among thousands.
      Surprisingly, ratings of the larger audience are predicted with greater accuracy
      than those of the individuals from whom the neural data is obtained. An
      additional functional magnetic resonance imaging study employing a separate
      sample of subjects shows that the level of neural reliability evoked by these
      stimuli covaries with the amount of blood-oxygenation-level-dependent (BOLD)
      activation in higher-order visual and auditory regions. Our findings suggest that
      stimuli which we judge favourably may be those to which our brains respond in a
      stereotypical manner shared by our peers. 

PMID- 25072835
TI  - Developing a general interaction potential for hydrophobic and hydrophilic
      interactions.
AB  - We review direct force measurements on a broad class of hydrophobic and
      hydrophilic surfaces. These measurements have enabled the development of a
      general interaction potential per unit area, W(D) = -2gamma(i)Hy exp(-D/D(H)) in
      terms of a nondimensional Hydra parameter, Hy, that applies to both hydrophobic
      and hydrophilic interactions between extended surfaces. This potential allows one
      to quantitatively account for additional attractions and repulsions not included
      in the well-known combination of electrostatic double layer and van der Waals
      theories, the so-called Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The
      interaction energy is exponentially decaying with decay length D(H) ~ 0.3-2 nm
      for both hydrophobic and hydrophilic interactions, with the exact value of D(H)
      depending on the precise system and conditions. The pre-exponential factor
      depends on the interfacial tension, gamma(i), of the interacting surfaces and Hy.
      For Hy > 0, the interaction potential describes interactions between partially
      hydrophobic surfaces, with the maximum hydrophobic interaction (i.e., two fully
      hydrophobic surfaces) corresponding to Hy = 1. Hydrophobic interactions between
      hydrophobic monolayer surfaces measured with the surface forces apparatus (SFA)
      are shown to be well described by the proposed interaction potential. The
      potential becomes repulsive for Hy < 0, corresponding to partially hydrophilic
      (hydrated) interfaces. Hydrated surfaces such as mica, silica, and lipid bilayers
      are discussed and reviewed in the context of the values of Hy appropriate for
      each system.

PMID- 25072834
TI  - Carica papaya microRNAs are responsive to Papaya meleira virus infection.
AB  - MicroRNAs are implicated in the response to biotic stresses. Papaya meleira virus
      (PMeV) is the causal agent of sticky disease, a commercially important pathology
      in papaya for which there are currently no resistant varieties. PMeV has a number
      of unusual features, such as residence in the laticifers of infected plants, and
      the response of the papaya to PMeV infection is not well understood. The protein
      levels of 20S proteasome subunits increase during PMeV infection, suggesting that
      proteolysis could be an important aspect of the plant defense response mechanism.
      To date, 10,598 plant microRNAs have been identified in the Plant miRNAs
      Database, but only two, miR162 and miR403, are from papaya. In this study, known
      plant microRNA sequences were used to search for potential microRNAs in the
      papaya genome. A total of 462 microRNAs, representing 72 microRNA families, were
      identified. The expression of 11 microRNAs, whose targets are involved in 20S and
      26S proteasomal degradation and in other stress response pathways, was compared
      by real-time PCR in healthy and infected papaya leaf tissue. We found that the
      expression of miRNAs involved in proteasomal degradation increased in response to
      very low levels of PMeV titre and decreased as the viral titre increased. In
      contrast, miRNAs implicated in the plant response to biotic stress decreased
      their expression at very low level of PMeV and increased at high PMeV levels.
      Corroborating with this results, analysed target genes for this miRNAs had their
      expression modulated in a dependent manner. This study represents a comprehensive
      identification of conserved miRNAs inpapaya. The data presented here might help
      to complement the available molecular and genomic tools for the study of papaya.
      The differential expression of some miRNAs and identifying their target genes
      will be helpful for understanding the regulation and interaction of PMeV and
      papaya. 

PMID- 25072836
TI  - Nitric oxide as a secondary messenger during stomatal closure as a part of plant
      immunity response against pathogens.
AB  - Stomata facilitate the loss of water, as well as CO2 uptake for photosynthesis.
      In addition, stomatal closure restricts the entry of pathogens into leaves and
      forms a part of plant defense response. Plants have evolved ways to modulate
      stomata by plant hormones as well as microbial elicitors, including
      pathogen/microbe associated molecular patterns. Stomatal closure initiated by
      signals of either abiotic or biotic factors results from the loss of guard cell
      turgor due mainly to K(+)/anion efflux. Nitric oxide (NO) is a key element among
      the signaling elements leading to stomatal closure, hypersensitive response and
      programmed cell death. Due to the growing importance of NO as signaling molecule
      in plants, and the strong relation between stomata and pathogen resistance, we
      attempted to present a critical overview of plant innate immunity, in relation to
      stomatal closure. The parallel role of NO during plant innate immunity and
      stomatal closure is highlighted. The cross-talk between NO and other signaling
      components, such as reactive oxygen species (ROS) is discussed. The possible
      sources of NO and mechanisms of NO action, through post-translational
      modification of proteins are discussed. The mini-review is concluded with remarks
      on the existing gaps in our knowledge and suggestions for future research. 

PMID- 25072837
TI  - Management of hypertriglyceridaemia-induced acute pancreatitis in pregnancy.
AB  - INTRODUCTION: Acute pancreatitis is a recognised rare complication in pregnancy.
      The reported incidence varies between 3 and 7 in 10 000 pregnancies and is higher
      in the third trimester. The commonest causes in pregnancy include gallstones,
      alcohol and hypertriglyceridaemia. Non-gallstone pancreatitis is associated with
      more complications and poorer outcome with hypertriglyceridaemia-induced acute
      pancreatitis having mortality rates ranging from 7.5 to 9.0% and 10.0 to 17.5%
      for mother and foetus, respectively. CASE HISTORY: A 40-year-old para 4 woman,
      who presented at 15(+4) weeks' gestation, was diagnosed with acute pancreatitis.
      Past medical history included Graves' disease and hypertriglyceridaemia.
      Fenofibrate was discontinued immediately after discovery of the pregnancy.
      Initial investigations showed elevated amylase (475.0 u/L) and triglycerides
      (46.6 mmol/L). Imaging revealed an inflamed pancreas without evidence of biliary
      obstruction/gallstones hence confirming the diagnosis of hypertriglyceridaemia
      induced acute pancreatitis. Laboratory tests gradually improved (triglyceride 5.2
      mmol/L on day 17). On day 18, ultrasound confirmed foetal demise (18(+1) weeks)
      and a hysterotomy was performed as she had had four previous caesarean sections.
      CONCLUSION: Management of acute pancreatitis in pregnancy requires a multi
      disciplinary approach. Hypertriglyceridaemia-induced acute pancreatitis has poor
      outcomes when diagnosed in early pregnancy. Identifying those at risk pre
      pregnancy and antenatally can allow close monitoring through pregnancy to
      optimise care.

PMID- 25072838
TI  - A new in vitro model using small intestinal epithelial cells to enhance infection
      of Cryptosporidium parvum.
AB  - To better understand and study the infection of the protozoan parasite
      Cryptosporidium parvum, a more sensitive in vitro assay is required. In vivo,
      this parasite infects the epithelial cells of the microvilli layer in the small
      intestine. While cell infection models using colon, kidney, and stomach cells
      have been studied to understand the infectivity potential of the oocysts, an
      ideal in vitro model would be readily-available, human-derived, and originating
      from the small intestine. In this study, we developed a reproducible,
      quantitative infection model using a non-carcinoma, human small intestinal
      epithelial cell type, named FHs 74 Int. Our results show that FHs 74 Int cells
      are productively infected by viable oocysts, and exhibit higher levels of
      infection susceptibility compared to other cell types. Moreover, infection rate
      of the sporozoites on the monolayer was found to be comparable or better than
      other cell types. We furthermore demonstrate that infection can be improved by
      65% when pre-treated oocysts are directly inoculated on cells, compared to
      inoculation of excysted sporozoites on cells. Identification of a better
      infection model, which captures the preferred site of infection in humans, will
      facilitate studies on the host pathogenesis mechanisms of this important
      parasitic human pathogen. 

PMID- 25072839
TI  - Evaluation of the MALDI-TOF VITEK MSTM system for the identification of Candida
      parapsilosis, C. orthopsilosis and C. metapsilosis from bloodstream infections.
AB  - Twenty-nine Candida parapsilosis, seventeen Candida orthopsilosis and two Candida
      metapsilosis bloodstream isolates were submitted for identification by VITEK-MSTM
      mass spectrometer. Four isolates, two C. orthopsilosis and two C. metapsilosis,
      were not identified. Inclusion of Superspectra of both species in this database
      is required to improve its discrimination power. 

PMID- 25072841
TI  - Talk to me.
AB  - While physicians and patients both turn to writing in order to reflect, heal and
      advocate for social change, few have the opportunity to write with one another. I
      met Ann Weber, a doctor in social psychology from Asheville, North Carolina, as a
      fourth year medical student on the wards. Both Ann and I continue to search for
      answers, but as inveterate learners and writers, we now heal and grow together.
      This piece offers insight into how simple actions during patient care can promote
      humanism and patient-centeredness in medicine.

PMID- 25072840
TI  - Pleural effusion lipoproteins measured by NMR spectroscopy for diagnosis of
      exudative pleural effusions: a novel tool for pore-size estimation.
AB  - High-resolution proton nuclear magnetic resonance (NMR) spectrometry of biofluids
      has been increasingly used in laboratory diagnosis of various diseases. In this
      study, we extended the use of (1)H NMR spectroscopy for laboratory diagnosis of
      exudative pleural effusions using pleural fluids. We compared this new NMR-based
      test with Light's criteria, the current gold standard for laboratory diagnosis of
      exudative pleural effusions. We analyzed 67 samples of pleural effusions from
      patients with pulmonary malignancy (N = 32), pulmonary tuberculosis (N = 18), and
      congestive heart failure (N = 17). The metabolomes of pleural effusions were
      analyzed using (1)H NMR spectroscopy on a Bruker 600 MHz spectrometer. Through a
      metabolome-wide association approach with filtering of insignificant markers (p
      value <4 * 10(-6)) and multivariate analysis (principal component analysis and
      orthogonal partial least squares-discriminant analysis), lipoprotein was found to
      be the best biomarker that distinguished exudates from transudates. Using NMR
      based lipoprotein profiling to classify exudative pleural effusions from
      transudates, the area-under-receiver operating characteristic (ROC) curve was
      0.96 with sensitivity of 98%, specificity of 88%, and accuracy of 98%. In
      contrast, the current gold standard, Light's criteria, give a specificity of only
      65% at the same sensitivity level of 98%. Using the principle of size exclusion,
      NMR-based lipoprotein profiling of pleural fluids has an unprecedented diagnostic
      performance superiority over the Light's criteria. The capillary leaks secondary
      to inflammation result in a larger pleural pore-size, which allows the large
      sized lipoproteins to accumulate in exudative pleural effusions. In contrast, the
      pleural permeability is intact in transudates, which allow only small-sized
      lipoproteins to pass into the pleural effusions. The average capillary pore-size
      of the pleura can therefore be determined by using NMR-based lipoprotein
      profiling of pleural fluids. We believe this new test will change the current
      clinical practice for management of pleural effusions and will become a new
      standard for clinical practice. 

PMID- 25072843
TI  - Development and validation of a highly sensitive LC-MS/MS assay for the
      quantification of arginine vasopressin in human plasma and urine: Application in
      preterm neonates and child.
AB  - Arginine vasopressin is an endogenous neuropeptide secreted in response to
      situations such as hyperosmolality, hypotension and hypovolemia. The purpose of
      this study was to develop a reliable assay using small volumes of plasma and
      urine samples to quantify vasopressin levels in preterm infants. Weak cation
      solid-phase extraction was used to extract vasopressin from 200MUl human plasma
      and urine samples. Separation was achieved on a Waters Acquity UPLC BEH C18
      column by gradient elution at 0.55ml/min, with a mobile phase composed of
      methanol and 0.02% aqueous acetic acid solution. Analysis was performed under a
      hybrid triple quadrupole linear ion trap mass spectrometer, operated in multiple
      reaction monitoring mode using positive ionization. The linear response range was
      1.0-40pg/ml for vasopressin, with the lower limit of quantification (LLOQ) of
      1.0pg/ml in human plasma and urine. Recoveries at concentrations of 3, 10 and
      32pg/ml were all greater than 70%, and matrix effects were within 15%. The method
      was validated with intra-day and inter-day precision of less than 8% for human
      plasma and urine. The intra-day and inter-day accuracy for human plasma were 91.9
      100.6% and 92.3-104.8%, respectively. The intra-day and inter-day accuracy for
      human urine were 89.2-95.9% and 89.3-91.3%, respectively. The validated method
      was successfully applied to analyze two preterm neonate plasma samples and one
      child urine sample. In conclusion, the developed and validated method was
      sensitive and reliable, and was successfully used to quantify endogenous
      vasopressin levels in neonate plasma and child urine. 

PMID- 25072842
TI  - Isolation and characterization of a novel acid degradation impurity of Amlodipine
      Besylate using Q-TOF, NMR, IR and single crystal X-ray.
AB  - Forced degradation of Amlodipine Besylate (AMD) in acidic condition gave rise to
      a potential unknown impurity. This unknown acid degradation product (ADP) was
      evaluated using a new-reverse-phase high performance liquid chromatography
      (HPLC), where it was eluted at 1.24 relative retention time to AMD peak. ADP was
      isolated using preparative HPLC from degradation mixture. Later, structure of ADP
      was elucidated using high resolution MS, multidimensional NMR and FTIR
      spectroscopic techniques, and characterized as ethyl-6-(2-chlorophenyl)-8-methyl
      3,4,6,7-tetrahydro-2H-benzo[b][1,4]oxazine-5-carboxylate. The presence of ADP
      recemic mixture was confirmed by polarimeter and chiral HPLC. Given the
      complexity associated with ADP generation, single crystal X-ray crystallography
      technique was used to confirm proposed structure. In addition, reaction mechanism
      was postulated and confirmed using computational chemistry. To our knowledge, it
      is a novel impurity and not reported elsewhere. 

PMID- 25072844
TI  - Teaching behaviors that define highest rated attending physicians: a study of the
      resident perspective.
AB  - BACKGROUND: Better understanding teaching behaviors of highly rated clinical
      teachers could improve training for teaching. We examined teaching behaviors
      demonstrated by higher rated attending physicians. METHODS: Qualitative and
      quantitative group consensus using the nominal group technique (NGT) among
      internal medicine residents and students on hospital services (2004-2005);
      participants voted on the three most important teaching behaviors (weight of 3 =
      top rated, 1 = lowest rated). Teaching behaviors were organized into domains of
      successful rounding characteristics. We used teaching evaluations to sort
      attending physicians into tertiles of overall teaching effectiveness. RESULTS:
      Participants evaluated 23 faculty in 17 NGT sessions. Participants identified 66
      distinct teaching behaviors (total sum of weights [sw] = 502). Nineteen items had
      sw >= 10, and these were categorized into the following domains: Teaching Process
      (n = 8; sw = 215, 42.8%), Learning Atmosphere (n = 5; sw = 145, 28.9%), Role
      Modeling (n = 3; sw = 74, 14.7%) and Team Management (n = 3; sw = 65, 12.9%).
      Attendings in the highest tertile received a larger number of votes for
      characteristics within the Teaching Process domain (56% compared to 39% in lowest
      tertile). CONCLUSIONS: The most effective teaching behaviors fell into two broad
      domains: Teaching Process and Learning Atmosphere. Highest rated attending
      physicians are most recognized for characteristics in the Teaching Process
      domain.

PMID- 25072845
TI  - A bifunctional converter: fluorescein quenching scFv/fluorogen activating protein
      for photostability and improved signal to noise in fluorescence experiments.
AB  - Monoclonal antibodies are one of the most useful and ubiquitous affinity reagents
      used in the biological sciences. Immunostaining of fixed and live cells for
      microscopy or cytometry measurements frequently employs fluorescently labeled
      antibodies, in particular fluorescein-labeled antibodies. This dye emits light at
      a wavelength overlapping with cellular autofluorescence, making it difficult to
      measure antibody binding to proteins of relatively low copy number or in cells of
      high green autofluorescence. A number of high affinity fluorescein binding
      antibodies and antibody domains have been developed that quench the dye's
      fluorescence. Using a fluorescein-binding recombinant antibody domain genetically
      fused to a fluorogen activating protein (FAP), we demonstrate a molecular
      converter capable of binding and quenching fluorescein, while binding and
      activating a fluorogenic triarylmethane dye. This reagent converts fluorescein
      conjugates to far-red fluorescent probes, where cellular autofluorescence is low,
      improving signal-to-background of cell-based antibody binding measurements by ~7
      fold. Microscopy experiments show colocalization of both fluorescein and MG
      fluorescence. This dual affinity fluorescein-quenching-FAP can also be used to
      convert fluorescein to the red fluorescing MG fluorogen on biological molecules
      other than antibodies. 

PMID- 25072846
TI  - Femtosecond spectroscopy of the dithiolate Cu(II) and Ni(II) complexes.
AB  - Femtosecond spectroscopy was applied to study the ultrafast dynamics for the
      excited states of dithiolate Cu(ii) and Ni(ii) complexes. The detailed
      information on the initial steps after the absorption of a photon by the metal
      complexes is of fundamental importance to understand the mechanism of
      photochemical reactions. The fast processes for the dithiolate complexes have
      hardly been studied. In this review the spectra of transients and their lifetimes
      will be presented. For example, the xanthogenate Ni(S2COEt)2 complex in
      acetonitrile and CCl4 after the pulse of the second harmonic (100 fs, 400 nm) of
      a Ti:S laser moves to the excited (1)LMCT state which decays in 0.76 ps to the
      excited (3)LF state. In 6.8 ps the (3)LF state undergoes vibrational cooling and
      then it slowly decays in 550 ps to the ground state. However, for many dithiolate
      complexes the kinetic curves can be well treated in a two-exponential
      approximation. A short time (less than 1 ps) may include several processes
      (relaxation of the Franck-Condon state, redistribution of vibrational energy
      (IVR), internal conversion (IC) and intersystem crossing (ISC)). A long time (a
      few picoseconds) usually reflects the vibrational cooling of the ground state.
      The quantum yields of the dithiolate and dithiolene complex disappearance in
      halogen containing solvents have a strong dependence on the wavelength of
      irradiation. It is very likely that electron transfer to the acceptor becomes
      effective when the electron in the excited complex moves to antibonding ligand
      orbitals localized at the periphery of the complex close to the acceptor molecule
      (halogenated solvent). 

PMID- 25072847
TI  - Efficient screening of long terminal repeat retrotransposons that show high
      insertion polymorphism via high-throughput sequencing of the primer binding site.
AB  - Retrotransposons have been used frequently for the development of molecular
      markers by using their insertion polymorphisms among cultivars, because multiple
      copies of these elements are dispersed throughout the genome and inserted copies
      are inherited genetically. Although a large number of long terminal repeat (LTR)
      retrotransposon families exist in the higher eukaryotic genomes, the
      identification of families that show high insertion polymorphism has been
      challenging. Here, we performed an efficient screening of these retrotransposon
      families using an Illumina HiSeq2000 sequencing platform with comprehensive LTR
      library construction based on the primer binding site (PBS), which is located
      adjacent to the 5' LTR and has a motif that is universal and conserved among LTR
      retrotransposon families. The paired-end sequencing library of the fragments
      containing a large number of LTR sequences and their insertion sites was
      sequenced for seven strawberry (Fragaria * ananassa Duchesne) cultivars and one
      diploid wild species (Fragaria vesca L.). Among them, we screened 24 families
      with a "unique" insertion site that appeared only in one cultivar and not in any
      others, assuming that this type of insertion should have occurred quite recently.
      Finally, we confirmed experimentally the selected LTR families showed high
      insertion polymorphisms among closely related cultivars. 

PMID- 25072848
TI  - Cucurbitacin E induces cell cycle G2/M phase arrest and apoptosis in triple
      negative breast cancer.
AB  - Triple negative breast cancer (TNBC) is a highly aggressive form of breast cancer
      resistant to many common treatments. In this study, we compared the effects of 12
      phytochemical drugs on four cancer cell lines, and noticed that Cucurbitacin E
      (CuE) significantly inhibited TNBC cell growth by inducing cell cycle G2/M phase
      arrest and apoptosis. CuE reduced expression of Cyclin D1, Survivin, XIAP, Bcl2,
      and Mcl-1 in MDA-MB-468 and SW527, and within MDA-MB-468, CuE significantly
      increased activation of JNK and inhibited activation of AKT and ERK.
      Collectively, these results suggest that CuE may be a viable compound for
      developing novel TNBC therapeutics. 

PMID- 25072849
TI  - Anti-HDV IgM as a marker of disease activity in hepatitis delta.
AB  - BACKGROUND: Hepatitis delta frequently leads to liver cirrhosis and hepatic
      decompensation. As treatment options are limited, there is a need for biomarkers
      to determine disease activity and to predict the risk of disease progression. We
      hypothesized that anti-HDV IgM could represent such a marker. METHODS: Samples of
      120 HDV-infected patients recruited in an international multicenter treatment
      trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA
      IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and
      angiogenetic factors were measured using multiplex technology (Bio-Plex System).
      A second independent cohort of 78 patients was studied for the development of
      liver-related clinical endpoints (decompensation, HCC, liver transplantation or
      death; median follow up of 3.0 years, range 0.6-12). RESULTS: Anti-HDV IgM serum
      levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%)
      patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with
      histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST
      p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA
      levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While
      high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels,
      various other antiviral cytokines were negatively associated with anti-HDV IgM.
      Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the
      independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive
      patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05).
      CONCLUSIONS: Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap
      marker to determine disease activity in hepatitis delta which has prognostic
      implications. High anti-HDV IgM levels may indicate an activated interferon
      system but exhausted antiviral immunity.

PMID- 25072850
TI  - Biotransformed soybean extract (BSE) inhibits melanoma cell growth and viability
      in vitro: involvement of nuclear factor-kappa B signaling.
AB  - Melanoma is recognized as one of the most aggressive cancers with a relatively
      high propensity for metastasis. The prognosis of melanoma remains poor in spite
      of treatment advances, emphasizing the importance of additional preventive
      measures. Isoflavonoids have become not only potential chemopreventive, but also
      important therapeutic natural agents. We evaluated the antiproliferative and
      proapoptotic properties of biotransformed soybean extract (BSE) in A375 melanoma
      cells. Previous analyses demonstrated that the concentration of daidzein,
      genistein and aminoacids/peptides present in BSE, fermented by Aspergillus
      awamori is much higher than in the non biotransformed extract (NBSE). Experiments
      comparing the efficacy of the extracts in preventing cancer cell growth showed
      that treatment (24 h) of aggressive melanoma cells (A375 and 451Lu) with BSE
      resulted in a dose-dependent inhibition of growth and viability. In contrast,
      treatment with similar doses of NBSE failed to inhibit melanoma cell viability.
      Further studies in A375 cells showed that decrease in cell viability with BSE
      treatment (1.5-1.9 mg/ml; 24 h) was associated with induction of apoptosis.
      Immunoblot analysis revealed that BSE treatment resulted in induction of PARP
      cleavage, activation of caspase-3, -7, and -8 and increased expression of TRAIL
      and its receptor DR4. BSE did not activate the intrinsic apoptotic pathway in
      A375 cells, as no change was observed in caspase-9 expression. The expression of
      Bcl-2 apoptotic proteins such as Bid and Bax remained unaffected with BSE treated
      cells. Interestingly, we also showed that BSE treatment increased the
      phosphorylation and activation of IKK, IkappaBalpha degradation and p65/NF-kappaB
      translocation to the nucleus, and that stimulation of the NF-???B pathway was
      required for BSE-induced apoptosis of A375 cells. Our findings indicate that the
      biotransformation of soybean plays a crucial role in the extract anti-cancer
      effect observed in melanoma cells. However, further studies are warranted to
      define the active anti-cancer agent(s) present in BSE. 

PMID- 25072851
TI  - SIRT2 deficiency modulates macrophage polarization and susceptibility to
      experimental colitis.
AB  - BACKGROUND: SIRT2 belongs to a highly conserved family of NAD+-dependent
      deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular
      localizations and have substrates ranging from histones to transcription factors
      and enzymes. Recently SIRT2 was revealed to play an important role in
      inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of
      NF-kappaB. METHODS: A Sirt2 deficient mouse line (Sirt2-/-) was generated by
      deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous
      recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were
      subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for
      colitis susceptibility. RESULTS: Sirt2-/- mice displayed more severe clinical and
      histological manifestations after DSS colitis compared to wild type littermates.
      Notably, under basal condition, Sirt2 deficiency does not affect the basal
      phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage
      polarization, creating a pro-inflammatory milieu in the immune cells compartment.
      CONCLUSION: These data confirm a protective role for SIRT2 against the
      development of inflammatory processes, pointing out a potential role for this
      sirtuin as a suppressor of colitis. In fact, SIRT2 deletion promotes inflammatory
      responses by increasing NF-kappaB acetylation and by reducing the M2-associated
      anti-inflammatory pathway. Finally, we speculate that the activation of SIRT2 may
      be a potential approach for the treatment of inflammatory bowel disease.

PMID- 25072852
TI  - The colonization dynamics of the gut microbiota in tilapia larvae.
AB  - The gut microbiota of fish larvae evolves fast towards a complex community. Both
      host and environment affect the development of the gut microbiota; however, the
      relative importance of both is poorly understood. Determining specific changes in
      gut microbial populations in response to a change in an environmental factor is
      very complicated. Interactions between factors are difficult to separate and any
      response could be masked due to high inter-individual variation even for
      individuals that share a common environment. In this study we characterized and
      quantified the spatio-temporal variation in the gut microbiota of tilapia larvae,
      reared in recirculating aquaculture systems (RAS) or active suspension tanks
      (AS). Our results showed that variation in gut microbiota between replicate tanks
      was not significantly higher than within tank variation, suggesting that there is
      no tank effect on water and gut microbiota. However, when individuals were reared
      in replicate RAS, gut microbiota differed significantly. The highest variation
      was observed between individuals reared in different types of system (RAS vs.
      AS). Our data suggest that under experimental conditions in which the roles of
      deterministic and stochastic factors have not been precisely determined,
      compositional replication of the microbial communities of an ecosystem is not
      predictable. 

PMID- 25072853
TI  - Stimulus motion improves spatial contrast sensitivity in budgerigars
      (Melopsittacus undulatus).
AB  - Birds are generally thought to have excellent vision with high spatial
      resolution. However, spatial contrast sensitivity of birds for stationary targets
      is low compared to other animals with similar acuity, such as mammals. For fast
      flying animals body stability and coordination are highly important, and visual
      motion cues are known to be relevant for flight control. We have tested five
      budgerigars (Melopsittacus undulatus) in behavioural discrimination experiments
      to determine whether or not stimulus motion improves contrast sensitivity. The
      birds were trained to distinguish between a homogenous grey field and sine-wave
      gratings of spatial frequencies between 0.48 and 6.5 cyc/deg, and Michelson
      contrasts between 0.7% and 99%. The gratings were either stationary or drifting
      with velocities between 0.9 and 13 deg/s. Budgerigars were able to discriminate
      patterns of lower contrast from grey when the gratings were drifting, and the
      improvement in sensitivity was strongest at lower spatial frequencies and higher
      drift velocities. Our findings indicate that motion cues can have positive
      effects on visual perception of birds. This is similar to earlier results on
      human vision. Contrast sensitivity, tested solely with stationary stimuli,
      underestimates the sensory capacity of budgerigars flying through their natural
      environments.

PMID- 25072855
TI  - A longitudinal study of alexithymia in relation to physical activity in
      adolescent females with scoliosis subjected to cheneau brace treatment:
      preliminary report.
AB  - STUDY DESIGN: A longitudinal pilot study of changes in levels of alexithymia
      among females with adolescent idiopathic scoliosis (AIS) under brace treatment.
      OBJECTIVE: To investigate the prevalence of alexithymia and to evaluate changes
      in alexithymia levels among female patients with AIS treated with a Cheneau
      brace, in comparison with healthy female adolescents. SUMMARY OF BACKGROUND DATA:
      Alexithymia is a personality trait incorporating the following core
      characteristics: difficulty in identifying and describing feelings, difficulty in
      distinguishing between feelings and the physical sensation of emotional arousal,
      limited imaginal processes, and an externally oriented cognitive style.
      Alexithymia can be common among adolescents and young adults with severe
      idiopathic scoliosis. METHODS: Thirty-six female patients with AIS, aged 13.4
      years (standard deviation [SD], 1.7) at the beginning of the study, completed the
      Polish version of the Toronto Alexithymia Scale-26 (TAS-26). The second and third
      evaluations took place at 6 and 12 months, respectively, after the beginning of
      the study. Thirty-six healthy female controls were also included. RESULTS: The
      mean TAS-26 total score was 63.4 (SD, 9.3), 59.5 (SD, 12.1), and 59.6 (SD, 12.5)
      during the first, second, and last patient evaluation, whereas in healthy females
      60.0 (SD, 10.9). With regard to the TAS-26 total score, results differed
      significantly between the first and the second (P = 0.007) and between the first
      and the third patient evaluation (P = 0.007). Regression analysis revealed that
      during the second and third patient evaluation, duration of recreational sports
      activity had a statistically significant (P = 0.029 and P = 0.005, respectively)
      influence on the probability of females reporting no alexithymia. CONCLUSION: The
      prevalence of alexithymia in healthy female controls is the same as in patients
      with scoliosis subjected to underarm brace treatment. Statistically significant
      changes with regard to TAS-26 total score and externally oriented thinking domain
      were found in patient sample. Physical activity in females with AIS treated
      nonoperatively coexists with lower scores in the TAS-26. LEVEL OF EVIDENCE: 2.

PMID- 25072854
TI  - Gene expression signatures in tree shrew choroid in response to three myopiagenic
      conditions.
AB  - We examined gene expression in tree shrew choroid in response to three different
      myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and
      continuous darkness (DK). Four groups of tree shrews (n=7 per group) were used.
      Starting 24 days after normal eye opening (days of visual experience [DVE]), the
      ML group wore a monocular -5D lens for 2 days. The FD group wore a monocular
      translucent diffuser for 2 days. The DK group experienced continuous darkness
      binocularly for 11 days, starting at 17 DVE. An age-matched normal group was
      examined at 26 DVE. Quantitative PCR was used to measure the relative (treated
      eye vs. control eye) differences in mRNA levels in the choroid for 77 candidate
      genes. Small myopic changes were observed in the treated eyes (relative to the
      control eyes) of the ML group (-1.0+/-0.2D; mean+/-SEM) and FD group (-1.9+/
      0.2D). A larger myopia developed in the DK group (-4.4+/-1.0D) relative to Normal
      eyes (both groups, mean of right and left eyes). In the ML group, 28 genes showed
      significant differential mRNA expression; eighteen were down-regulated. A very
      similar pattern occurred in the FD group; twenty-seven of the same genes were
      similarly regulated, along with five additional genes. Fewer expression
      differences in the DK group were significant compared to normal or the control
      eyes of the ML and FD groups, but the pattern was similar to that of the ML and
      FD differential expression patterns. These data suggest that, at the level of the
      choroid, the gene expression signatures produced by "GO" emmetropization signals
      are highly similar despite the different visual conditions.

PMID- 25072857
TI  - Water extract from Pleurotus pulmonarius with antioxidant activity exerts in vivo
      chemoprophylaxis and chemosensitization for liver cancer.
AB  - Chemoprophylaxis and chemosensitization are promising strategies to combat human
      cancers. Natural antioxidant agents show great promise in cancer therapy, and the
      use of edible mushrooms against cancer is receiving more interest globally. In
      this study, the radical scavenging activities including diphenyl-1
      picrylhydrazyl, superoxide anion radical, hydroxyl radical, and hydrogen peroxide
      were compared among hot water extracts from 3 edible mushrooms, among which
      Pleurotus pulmonarius (Pp) possessed the highest antioxidant potential. Oral
      administration of Pp 2 wk in advance could markedly inhibit the incidence and
      size of tumor (Huh7 liver cancer cells) with an inhibition rate of 93.1% in nude
      mice. No obvious side effect was observed in the Pp-treated mice as indicated by
      their body weight and histological analysis of major organs. The cancer
      prevention by Pp treatment might be explained by the inhibition of cancer cell
      proliferation indicated by reduction of ki-67 staining and the inactivation of
      phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in the Pp-treated mice.
      Furthermore, a significant synergistic effect was observed when the mice were
      treated with a combination of low dose of cisplatin and Pp. Taken together, these
      results suggest the potential application of Pp as an adjuvant in the
      chemotherapy of liver cancer. 

PMID- 25072858
TI  - [No correlation between vitamin D and 137 diseases--Vitamin D: a long way to go
      to clinical practice].

PMID- 25072859
TI  - [No correlation between vitamin D and 137 diseases--What is the benefit of
      systematically reviewing systematic reviews?].

PMID- 25072860
TI  - [Echocardiography and right heart catheterization in pulmonal hypertension].
AB  - BACKGROUND AND OBJECTIVE: Since pulmonary hypertension is defined
      haemodynamically with a mean pulmonary artery pressure (mPAP) of at least 25
      mmHg, right heart catheterization is mandatory for diagnosis of PH. However, it
      remains unclear if echocardiography can always detect a PH and to what extent
      echocardiographic and invasive parameters correlate. We aimed to determine the
      frequency of right heart valve insufficiencies, the correlation of mPAP measured
      invasively and estimated by echocardiography and the correlation of other
      echocardiographic parameters with invasively measured cardiac output (CO) and
      pulmonary vascular resistance (PVR) in patients who presented at our center for
      pulmonary hypertension. METHODS: Retrospective analysis of echocardiographic and
      invasively measured parameters in consecutive patients who presented with dyspnea
      and suspected PH. RESULTS: 10% of the patients with invasively confirmed PH had
      no tricuspid valve insufficiency, 61.3% had no pulmonary valve insufficiency. The
      highest correlation of invasively measured mPAP was found for mPAP estimated non
      invasively via RVSP (R = 0.80; < 0.0001). Correlation of non-invasively estimated
      mPAP by the pulmonary valve regurgitation (R = 0,72, p < 0,004) and mPAP measured
      by the right ventricular outflow tract flow acceleration time (R = 0,54, p <
      0.0001) with invasively measured mPAP were inferior. Left ventricular
      eccentricity index and systolic tissue Doppler velocity of tricuspid annulus
      correlated highly significant with PVR, TAPSE correlated with PVR and CO. Right
      ventricular myocardial performance index correlated with CO. CONCLUSION: In 10%
      of invasively proven PH, the diagnosis can be missed by estimation of RVSP by
      echocardiography alone, due to a lack of tricuspid valve insufficiency.
      Echocardiographic assessment of mPAP remains difficult. Echocardiography can
      deliver qualitative information about CO and PVR. Right heart catheterization
      remains mandatory to confirm or to rule out PH.

PMID- 25072861
TI  - [Hyperammonemic encephalopathy in multiple myeloma].
AB  - HISTORY AND CLINICAL FINDINGS: A 54-year old man had suffered from advanced
      multiple myeloma for two years. After initially good response the myeloma was
      refractrory to treatment with dexamethasone, cyclophosphamide, bortezomibe,
      zoledronate and additionally doxorubicine. The patient then complained of dyspnea
      without clinical signs of cardiopulmonary disease. INVESTIGATIONS: Arterial blood
      gas analysis showed hyperventilation with respiratory alkalosis and normal
      alveolo-arterial gradient as the reason for the dyspnea. With a normal MRI of the
      brain and lumbal puncture, a neurological disease could be excluded. Serum
      calcium, creatinine and serum viscosity were normal. Eventually, serum ammonia
      levels were found to be substantially elevated (144 umol/l) and hyperammonemic
      encephalopathy was diagnosed. TREATMENT AND COURSE: Therapy with bortezomib and
      high dose dexamethason was repeated, and the patient also received bendamustin.
      Despite this treatment, he lost consciousness and died after two weeks because of
      aspiration pneumonia. CONCLUSION: The existence of respiratory alkalosis and
      multiple myeloma should prompt a search for hyperammonemia.

PMID- 25072862
TI  - [26-year old man with chest pain and unspecific athralgia].

PMID- 25072863
TI  - [Vaginal bleeding as symptom of a medical emergency--pitfalls of therapy with new
      oral anticoagulants - case 5/2014].
AB  - HISTORY AND ADMISSION FINDINGS: A 90-year-old female patient treated with
      dabigatran for atrial fibrillation presented emergently with a spontaneous
      vaginal bleeding due to endometrium carcinoma. INVESTIGATIONS: Laboratory
      analysis revealed azotemia consistent with acute-on-chronic renal failure.
      Coagulation was deranged (prolongation of activated partial thromboplastin time
      (aPTT) by 3.5-fold, international normalized ratio (INR) 7.8) due to a massive
      accumulation of dabigatran (measured plasma concentration 2230 ng/ml). DIAGNOSIS,
      TREATMENT AND COURSE: Vaginal bleedings were treated with external tamponade.
      Hemodialysis treatment was commenced due to uremia and dabigatran accumulation.
      Over night, the patient was dialysed with a SLED (sustained low efficiency
      dialysis) regimen. After volume resuscitation renal function promptly ensued
      indicating prerenal azotemia as a cause of renal failure. After two more
      hemodialysis sessions dabigatran concentrations were no longer detecable and this
      was paralleled by normalization of coagulation tests. CONCLUSIONS: Dabigatran can
      accumulate massively during acute renal failure and evoke a life-threatening
      bleeding diathesis. Dabigatran can be removed with low efficient dialysis (such
      as SLED).

PMID- 25072864
TI  - [Management of mesenteric ischemia and mesenteric vein thrombosis].
AB  - Acute mesenteric ischemia is secondary to acute embolic disease or thrombosis of
      the superior mesenteric artery. Further pathologies that manifest themselves with
      the same clinical presentation are thrombosis of the superior mesenteric vein and
      non-occlusive disease. The patients are admitted to the emergency room with an
      acute abdomen. Most patients are more than 70 years old. Known risk factors for
      mesenteric ischemia are cardiac diseases as atrial fibrillation, aneurysms of the
      aorta and the visceral arteries, occlusive arterial diseases, tumorigenic
      compression of the vessel and several diseases that result in a reduction of the
      flow and intravascular volume in the superior mesenteric artery. The golden
      standard in the diagnosis of acute mesenteric ischemia is CT-angiography of the
      abdominal vessels with 3 D reconstruction. The therapy is different and dependent
      from the underlying pathology. A statistically significantly elevated mortality
      of more than 95% is associated with a delay of surgical or interventional therapy
      of more than 12 hours after the initial symptoms and non-occlusive mesenteric
      ischemia. Because of the advanced age of the patients and the co-morbidities a
      non-surgical interventional re-canalisation of the superior mesenteric vessels is
      recommended. A laparotomy is necessary in all patients with peritonitis and/or
      bowel necrosis or perforation.

PMID- 25072865
TI  - A key role of the mitochondrial citrate carrier (SLC25A1) in TNFalpha- and
      IFNgamma-triggered inflammation.
AB  - The chronic induction of inflammation underlies multiple pathological conditions,
      including metabolic, autoimmune disorders and cancer. The mitochondrial citrate
      carrier (CIC), encoded by the SLC25A1 gene, promotes the export of citrate from
      the mitochondria to the cytoplasm, a process that profoundly influences energy
      balance in the cells. We have previously shown that SLC25A1 is a target gene for
      lipopolysaccharide signaling and promotes the production of inflammatory
      mediators. We now demonstrate that SLC25A1 is induced at the transcriptional
      level by two key pro-inflammatory cytokines, tumor necrosis factor-alpha
      (TNFalpha) and interferon-gamma (IFNgamma), and such induction involves the
      activity of the nuclear factor kappa B and STAT1 transcription factors. By
      studying the down-stream events following SLC25A1 activation during signals that
      mimic inflammation, we demonstrate that CIC is required for regulating the levels
      of nitric oxide and of prostaglandins by TNFalpha or IFNgamma. Importantly, we
      show that the citrate exported from mitochondria via CIC and its downstream
      metabolic intermediate, acetyl-coenzyme A, are necessary for TNFalpha or IFNgamma
      to induce nitric oxide and prostaglandin production. These findings provide the
      first line of evidence that the citrate export pathway, via CIC, is central for
      cytokine-induced inflammatory signals and shed new light on the relationship
      between energy metabolism and inflammation. 

PMID- 25072866
TI  - Prevalence and mapping of a plasmid encoding a type IV secretion system in
      Acinetobacter baumannii.
AB  - We investigated the prevalence of a type IV secretion system (T4SS)-bearing
      plasmid among clinical isolates of carbapenem-resistant Acinetobacter baumannii
      (CRAB) using plasmid replicon typing. The complete sequence of a T4SS-bearing
      plasmid, pAB_CC, isolated from A. baumannii TYTH-1 was determined, and a
      comparative analysis of the T4SS gene modules was performed. Of the 129 isolates
      studied, GR6 (repAci6) was the most common (45 of 96 isolates) and was strongly
      linked with the T4SS. A comparative analysis of the T4SS locus in seven plasmid
      genomes, including pAB_CC, pACICU2, pABKp1, pABTJ1, p1BJAB0714, p2BJAB0868, and
      p2ABTCDC0715, indicated that fourteen genes on these plasmids were highly
      conserved compared to those of the F plasmid. Additionally, the chromosomes in
      the seven representative isolates may be evolutionarily distinct from their
      intrinsic T4SS-bearing plasmids, suggesting that the two T4SS lineages emerged
      long before the appearance of EC II. These two lineages are now widespread in A.
      baumannii strains. 

PMID- 25072867
TI  - An effective dispersant for oil spills based on food-grade amphiphiles.
AB  - Synthetic dispersants such as Corexit 9500A were used in large quantities (~2
      million gallons) to disperse the oil spilled in the ocean during the recent
      Deepwater Horizon event. These dispersant formulations contain a blend of
      surfactants in a base of organic solvent. Some concerns have been raised
      regarding the aquatic toxicity and environmental impact of these formulations. In
      an effort to create a safer dispersant, we have examined the ability of food
      grade amphiphiles to disperse (emulsify) crude oil in seawater. Our studies show
      that an effective emulsifier is obtained by combining two such amphiphiles:
      lecithin (L), a phospholipid extracted from soybeans, and Tween 80 (T), a
      surfactant used in many food products including ice cream. Interestingly, we find
      that L/T blends show a synergistic effect, i.e., their combination is an
      effective emulsifier, but neither L or T is effective on its own. This synergy is
      maximized at a 60/40 weight ratio of L/T and is attributed to the following
      reasons: (i) L and T pack closely at the oil-water interface; (ii) L has a low
      tendency to desorb, which fortifies the interfacial film; and (iii) the large
      headgroup of T provides steric repulsions between the oil droplets and prevents
      their coalescence. A comparison of L/T with Corexit 9500A shows that the former
      leads to smaller oil droplets that remain stable to coalescence for a much longer
      time. The smaller size and stability of crude oil droplets are believed to be
      important to their dispersion and eventual microbial degradation in the ocean.
      Our findings suggest that L/T blends could potentially be a viable alternative
      for the dispersion of oil spills. 

PMID- 25072868
TI  - On the risk concerns of zacopride, a moderate IK1 channel agonist with cardiac
      protective action.
AB  - Zacopride, an IK1 agonist with moderate potency, could exert significant
      antiarrhythmic and cardiac protective effects. To date, there is no report to
      show that zacopride is proarrhythmic in both experimental studies and clinical
      trials. However, in certain cardiac pathological conditions, especially short QT
      syndrome and certain reentry tachycardia, zacopride is not suggested. Further
      studies are needed to precisely evaluate the potential arrhythmogenic risk of
      zacopride.

PMID- 25072869
TI  - Ion-based assemblies of planar anion complexes and cationic Pt(II) complexes.
AB  - Because the metallophilicity of attractive Pt(II)...Pt(II) interactions helps in
      the fabrication of columnar structures, terpyridine-Pt(II) complexes were used as
      planar counter cationic species for formation of charge-segregated assemblies
      using pi-conjugated receptor-Cl(-) complexes as planar anions.

PMID- 25072870
TI  - Monitoring penetratin interactions with lipid membranes and cell internalization
      using a new hydration-sensitive fluorescent probe.
AB  - A new fluorescent label N-[4'-(dimethylamino)-3-hydroxyflavone-7-yl]-N-methyl
      beta-alanine (7AF) was synthesized. Due to two electron donor groups at the
      opposite ends of the chromophore, an excited state intramolecular proton transfer
      (ESIPT) resulting in a dual emission was observed even in highly polar media and
      its fluorescence quantum yield was found to be remarkably high in a broad range
      of solvents including water. As a consequence, this label exhibits a remarkable
      sensitivity to the hydration of its environment, which is observed as a color
      switch between the emission of the ESIPT product (T* form) and that of the normal
      N* form. The 7AF label was coupled to the N-terminus of penetratin, a cell
      penetrating peptide, in order to study its interactions with lipid membranes and
      internalization inside the cells. As expected, the binding of penetratin to lipid
      membranes resulted in a dramatic switch in the relative intensity of its two
      emission bands as compared to its emission in buffer. Our studies with different
      lipid compositions confirmed the preference of penetratin to lipid membranes of
      the liquid disordered phase. After incubation of low concentrations of labeled
      penetratin with living cells, ratiometric imaging revealed, in addition to
      membrane-bound species, a significant fraction of free peptide in cytosol showing
      the characteristic emission from aqueous medium. At higher concentrations of
      penetratin, mainly peptides bound to cell membrane structures were observed.
      These observations confirmed the ability of penetratin to enter the cytosol by
      direct translocation through the cell plasma membrane, in addition to the
      classical entry by endocytosis. The present probe constitutes thus a powerful
      tool to study the interaction of peptides with living cells and their
      internalization mechanisms.

PMID- 25072872
TI  - Self-catalyzed carbon dioxide adsorption by metal-organic chains on gold
      surfaces.
AB  - Efficient capture of CO2 by chemical means requires a microscopic understanding
      of the interactions of the molecule-substrate bonding and adsorption-induced
      collective phenomena. By molecule-resolved imaging with scanning tunneling
      microscopy (STM), we investigate self-catalyzed CO2 adsorption on one-dimensional
      (1D) substrates composed of self-assembled metal-organic chains (MOCs) supported
      on gold surfaces. CO2 adsorption turns on attractive interchain interactions,
      which induce pronounced surface structural changes; the initially uniformly
      dispersed chains gather into close packed bundles, which are held together by
      highly ordered, single molecule wide CO2 ranks. CO2 molecules create more
      favorable adsorption sites for further CO2 adsorption by mediating the interchain
      attraction, thereby self-catalyzing their capture. The release of CO2 molecules
      by thermal desorption returns the MOCs to their original structure, indicating
      that the CO2 capture and release are reversible processes. The real space
      microscopic characterization of the self-catalyzed CO2 adsorption on 1D
      substrates could be exploited as platform for design of molecular materials for
      CO2 capture and reduction.

PMID- 25072871
TI  - Cementing proteins provide extra mechanical stabilization to viral cages.
AB  - The study of virus shell stability is key not only for gaining insights into
      viral biological cycles but also for using viral capsids in materials science.
      The strength of viral particles depends profoundly on their structural changes
      occurring during maturation, whose final step often requires the specific binding
      of 'decoration' proteins (such as gpD in bacteriophage lambda) to the viral
      shell. Here we characterize the mechanical stability of gpD-free and gpD
      decorated bacteriophage lambda capsids. The incorporation of gpD into the lambda
      shell imparts a major mechanical reinforcement that resists punctual
      deformations. We further interrogate lambda particle stability with molecular
      fatigue experiments that resemble the sub-lethal Brownian collisions of virus
      shells with macromolecules in crowded environments. Decorated particles are
      especially robust against collisions of a few kBT (where kB is the Boltzmann's
      constant and T is the temperature ~300 K), which approximate those anticipated
      from molecular insults in the environment. 

PMID- 25072873
TI  - Discovery of oxazole and triazole derivatives as potent and selective S1P(1)
      agonists through pharmacophore-guided design.
AB  - We have discovered a series of triazole/oxazole-containing 2-substituted 2
      aminopropane-1,3-diol derivatives as potent and selective S1P1 agonists
      (prodrugs) based on pharmacophore-guided rational design. Most compounds showed
      high affinity and selectivity for S1P1 receptor. Compounds 19b, 19d and 19p
      displayed clear dose responsiveness in the lymphocyte reduction model when
      administered orally at doses of 0.3, 1.0, 3.0 mg/kg with reduced effect on heart
      rate. These three compounds were also identified to have favorable
      pharmacokinetic properties. 

PMID- 25072874
TI  - 2,4,5-Trisubstituted thiazole derivatives: a novel and potent class of non
      nucleoside inhibitors of wild type and mutant HIV-1 reverse transcriptase.
AB  - Novel 2,4,5-trisubstituted thiazole derivatives (TSTs) were designed and
      synthesized as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs).
      Among the thirty-eight synthesized target compounds, thirty TSTs showed potent
      inhibition against HIV-1 replication in wild type HIV-1 at submicromolar
      concentrations (from 0.046 to 9.59 MUM). Compounds 21, 23 and 24 were also tested
      on seven NNRTI-resistant HIV-1 strains, and all exhibited inhibitory effects with
      fold changes in IC50 ranging from 2.6 to 111, which were better than those of
      nevirapine (15.6-fold-371-fold). Docking simulations of compound 24 revealed a
      reasonable mechanism for the binding mode, and three-dimensional quantitative
      structure activity relationship (3-DQSAR) studies on this novel series of TST
      further elucidated the structure-activity relationship (SAR). The results
      suggested the great potential of TSTs as a novel class of NNRTIs with antiviral
      efficacy and a good resistance profile. 

PMID- 25072875
TI  - Nanoliposomes presenting on surface a cis-glycofused benzopyran compound display
      binding affinity and aggregation inhibition ability towards Amyloid beta1-42
      peptide.
AB  - Nanoliposomes decorated on their surface with ligands for Abeta-peptides, the key
      morphological features of Alzheimer's disease (AD), have been synthesized and
      characterized for their ability to target Abeta-peptide aggregates. A tricyclic
      benzopyrane-glycofused structure has been exploited as Abeta-peptide ligand,
      which was linked to liposomes via a copper-free, chemoselective, biocompatible
      click chemistry reaction. The tricyclic-decorated liposomes presented a mean
      diameter in the nanomolar range (150-200 nm), a negative z-potential and a good
      stability, at least up to one month. Integrity studies performed in the presence
      of serum proteins indicated that these decorated nanoliposomes fulfill the
      requirements for in vivo applications. NMR experiments carried out with Abeta1-42
      oligomers using both surface functionalized and plain (control) liposomes,
      revealed that the binding ability of the nanoliposomes was mediated by the
      presence of the tricyclic ligand on their surface. Finally ThT assay carried out
      with tricyclic-decorated liposomes showed significant decrease in thioflavine T
      fluorescence after 24 h, suggesting a significant inhibition/delay of Abeta1-42
      aggregation. 

PMID- 25072876
TI  - Trends in research of antitrypanosomal agents among synthetic heterocycles.
AB  - To date treatment of trypanosomiasis urgently requires new effective and non
      toxic drugs. The article covers some of the achievements in the search for new
      antitrypanosomal agents; also the "validated" biological targets used in the
      antitrypanosomal agents design are outlined. The major part of the manuscript
      focuses on the synthetic small molecules, such as thiosemicarbazone and thiazole
      (as their cyclic analogues) derivatives, benzofuran derivatives, heterocycles
      bearing nitro group etc. Also, the attractiveness of metal complexes and well
      known drugs as sources for antitrypanosomal agent design is discussed. 

PMID- 25072877
TI  - One-pot heterogeneous synthesis of Delta(3)-tetrahydrocannabinol analogues and
      xanthenes showing differential binding to CB(1) and CB(2) receptors.
AB  - Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is the major psychoactive
      cannabinoid in hemp (Cannabis sativa L.) and responsible for many of the
      pharmacological effects mediated via cannabinoid receptors. Despite being the
      major cannabinoid scaffold in nature, Delta(9)-THC double bond isomers remain
      poorly studied. The chemical scaffold of tetrahydrocannabinol can be assembled
      from the condensation of distinctly substituted phenols and monoterpenes. Here we
      explored a microwave-assisted one pot heterogeneous synthesis of Delta(3)-THC
      from orcinol (1a) and pulegone (2). Four Delta(3)-THC analogues and corresponding
      Delta(4a)-tetrahydroxanthenes (Delta(4a)-THXs) were synthesized regioselectively
      and showed differential binding affinities for CB1 and CB2 cannabinoid receptors.
      Here we report for the first time the CB1 receptor binding of Delta(3)-THC,
      revealing a more potent receptor binding affinity for the (S)-(-) isomer (hCB1Ki
      = 5 nM) compared to the (R)-(+) isomer (hCB1Ki = 29 nM). Like Delta(9)-THC, also
      Delta(3)-THC analogues are partial agonists at CB receptors as indicated by
      [(35)S]GTPgammaS binding assays. Interestingly, the THC structural isomers
      Delta(4a)-THXs showed selective binding and partial agonism at CB2 receptors,
      revealing a simple non-natural natural product-derived scaffold for novel CB2
      ligands. 

PMID- 25072878
TI  - Access points for the underserved: primary care appointment availability at
      federally qualified health centers in 10 States.
AB  - BACKGROUND: Federally Qualified Health Centers (FQHCs) are a vital source of
      primary care for underserved populations, such as Medicaid enrollees and the
      uninsured. Their role in delivering care may increase through new funding
      allocations in the Affordable Care Act and expanded Medicaid programs across many
      states. OBJECTIVE: Examine differences in appointment availability and wait-times
      for new patient visits between FQHCs and other providers. RESEARCH DESIGN: We use
      experimental data from a simulated patient study to compare new patient
      appointment rates across FQHC and non-FQHC practices for 3 insurance types
      (private, Medicaid, and self-pay). Trained auditors, posing as patients
      requesting the first available new patient appointment, were randomized to call
      primary care providers in 10 states in late 2012 and early 2013. Multivariate
      regression models adjust for caller-level, clinic-level, and area-level
      variables. STUDY SETTING: The sample comprises 10,904 calls, including 544 calls
      to FQHCs. RESULTS: FQHCs grant new patient appointments at high rates,
      irrespective of patient insurance status. Adjusting for caller, clinic, and area
      variables, the Medicaid appointment rate at FQHCs is 22 percentage points higher
      than other primary care practices. Although the appointment rate difference
      between FQHCs and non-FQHCs is somewhat smaller for the self-pay group, FQHCs are
      much more likely to provide a lower-cost visit to these patients. Conditional on
      receiving an appointment, wait-times at FQHCs are comparable with other
      providers. CONCLUSION: FQHCs' greater willingness to accept new underserved
      patients before 2014 underscores their potential key roles as health reform
      proceeds.

PMID- 25072879
TI  - Photo-antagonism of the GABAA receptor.
AB  - Neurotransmitter receptor trafficking is fundamentally important for synaptic
      transmission and neural network activity. GABAA receptors and inhibitory synapses
      are vital components of brain function, yet much of our knowledge regarding
      receptor mobility and function at inhibitory synapses is derived indirectly from
      using recombinant receptors, antibody-tagged native receptors and pharmacological
      treatments. Here we describe the use of a set of research tools that can
      irreversibly bind to and affect the function of recombinant and neuronal GABAA
      receptors following ultraviolet photoactivation. These compounds are based on the
      competitive antagonist gabazine and incorporate a variety of photoactive groups.
      By using site-directed mutagenesis and ligand-docking studies, they reveal new
      areas of the GABA binding site at the interface between receptor beta and alpha
      subunits. These compounds enable the selected inactivation of native GABAA
      receptor populations providing new insight into the function of inhibitory
      synapses and extrasynaptic receptors in controlling neuronal excitation. 

PMID- 25072881
TI  - Is the effect of surface modifying molecules on antibacterial activity universal
      for a given material?
AB  - Antibacterial activity of nanomaterials is strongly dependent on their
      properties, and their stability and toxicity can be varied using surface
      coatings. We investigated the effect of different surface modifying molecules on
      the antibacterial properties of two ZnO nanoparticle samples. We found that the
      starting surface properties of the nanoparticles have significant effects on the
      attachment of the surface modifying molecules and consequent antibacterial
      activity. Two out of five investigated surface modifying molecules not only had a
      significant difference in the magnitude of their effect on different
      nanoparticles, but also resulted in the opposite effects on two ZnO nanoparticle
      samples (an enhancement of antibacterial activity for one and a reduction of
      antibacterial activity for the other ZnO sample). This indicates that no general
      rule on the effect of a specific molecule on the toxicity of a metal oxide
      nanoparticle can be derived without knowing the nanoparticle properties, due to
      the fact that surface modifier attachment onto the surface is affected by the
      initial surface properties. 

PMID- 25072880
TI  - Chronic artificial blue-enriched white light is an effective countermeasure to
      delayed circadian phase and neurobehavioral decrements.
AB  - Studies in Polar Base stations, where personnel have no access to sunlight during
      winter, have reported circadian misalignment, free-running of the sleep-wake
      rhythm, and sleep problems. Here we tested light as a countermeasure to circadian
      misalignment in personnel of the Concordia Polar Base station during the polar
      winter. We hypothesized that entrainment of the circadian pacemaker to a 24-h
      light-dark schedule would not occur in all crew members (n = 10) exposed to 100
      300 lux of standard fluorescent white (SW) light during the daytime, and that
      chronic non-time restricted daytime exposure to melanopsin-optimized blue
      enriched white (BE) light would establish an a stable circadian phase, in
      participants, together with increased cognitive performance and mood levels. The
      lighting schedule consisted of an alternation between SW lighting (2 weeks),
      followed by a BE lighting (2 weeks) for a total of 9 weeks. Rest-activity cycles
      assessed by actigraphy showed a stable rest-activity pattern under both SW and BE
      light. No difference was found between light conditions on the intra-daily
      stability, variability and amplitude of activity, as assessed by non-parametric
      circadian analysis. As hypothesized, a significant delay of about 30 minutes in
      the onset of melatonin secretion occurred with SW, but not with BE light. BE
      light significantly enhanced well being and alertness compared to SW light. We
      propose that the superior efficacy of blue-enriched white light versus standard
      white light involves melanopsin-based mechanisms in the activation of the non
      visual functions studied, and that their responses do not dampen with time (over
      9-weeks). This work could lead to practical applications of light exposure in
      working environment where background light intensity is chronically low to
      moderate (polar base stations, power plants, space missions, etc.), and may help
      design lighting strategies to maintain health, productivity, and personnel
      safety. 

PMID- 25072882
TI  - Scientific debate is an opportunity, not a chore: it benefits the establishment,
      the heretic, and the observer alike.

PMID- 25072884
TI  - Inter-model comparison of the landscape determinants of vector-borne disease:
      implications for epidemiological and entomological risk modeling.
AB  - Extrapolating landscape regression models for use in assessing vector-borne
      disease risk and other applications requires thoughtful evaluation of fundamental
      model choice issues. To examine implications of such choices, an analysis was
      conducted to explore the extent to which disparate landscape models agree in
      their epidemiological and entomological risk predictions when extrapolated to new
      regions. Agreement between six literature-drawn landscape models was examined by
      comparing predicted county-level distributions of either Lyme disease or Ixodes
      scapularis vector using Spearman ranked correlation. AUC analyses and multinomial
      logistic regression were used to assess the ability of these extrapolated
      landscape models to predict observed national data. Three models based on
      measures of vegetation, habitat patch characteristics, and herbaceous landcover
      emerged as effective predictors of observed disease and vector distribution. An
      ensemble model containing these three models improved precision and predictive
      ability over individual models. A priori assessment of qualitative model
      characteristics effectively identified models that subsequently emerged as better
      predictors in quantitative analysis. Both a methodology for quantitative model
      comparison and a checklist for qualitative assessment of candidate models for
      extrapolation are provided; both tools aim to improve collaboration between those
      producing models and those interested in applying them to new areas and research
      questions. 

PMID- 25072883
TI  - Natural selection on individual variation in tolerance of gastrointestinal
      nematode infection.
AB  - Hosts may mitigate the impact of parasites by two broad strategies: resistance,
      which limits parasite burden, and tolerance, which limits the fitness or health
      cost of increasing parasite burden. The degree and causes of variation in both
      resistance and tolerance are expected to influence host-parasite evolutionary and
      epidemiological dynamics and inform disease management, yet very little empirical
      work has addressed tolerance in wild vertebrates. Here, we applied random
      regression models to longitudinal data from an unmanaged population of Soay sheep
      to estimate individual tolerance, defined as the rate of decline in body weight
      with increasing burden of highly prevalent gastrointestinal nematode parasites.
      On average, individuals lost weight as parasite burden increased, but whereas
      some lost weight slowly as burden increased (exhibiting high tolerance), other
      individuals lost weight significantly more rapidly (exhibiting low tolerance). We
      then investigated associations between tolerance and fitness using selection
      gradients that accounted for selection on correlated traits, including body
      weight. We found evidence for positive phenotypic selection on tolerance: on
      average, individuals who lost weight more slowly with increasing parasite burden
      had higher lifetime breeding success. This variation did not have an additive
      genetic basis. These results reveal that selection on tolerance operates under
      natural conditions. They also support theoretical predictions for the erosion of
      additive genetic variance of traits under strong directional selection and
      fixation of genes conferring tolerance. Our findings provide the first evidence
      of selection on individual tolerance of infection in animals and suggest
      practical applications in animal and human disease management in the face of
      highly prevalent parasites. 

PMID- 25072885
TI  - Ag nanocluster/DNA hybrids: functional modules for the detection of nitroaromatic
      and RDX explosives.
AB  - Luminescent Ag nanoclusters (NCs) stabilized by nucleic acids are implemented as
      optical labels for the detection of the explosives picric acid, trinitrotoluene
      (TNT), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The sensing modules
      consist of two parts, a nucleic acid with the nucleic acid-stabilized Ag NCs and
      a nucleic acid functionalized with electron-donating units, including L-DOPA, L
      tyrosine and 6-hydroxy-L-DOPA, self-assembled on a nucleic acid scaffold. The
      formation of donor-acceptor complexes between the nitro-substituted explosives,
      exhibiting electron-acceptor properties, and the electron-donating sites,
      associated with the sensing modules, concentrates the explosives in close
      proximity to the Ag NCs. This leads to the electron-transfer quenching of the
      luminescence of the Ag NCs by the explosive molecule. The quenching of the
      luminescence of the Ag NCs provides a readout signal for the sensing process. The
      sensitivities of the analytical platforms are controlled by the electron-donating
      properties of the donor substituents, and 6-hydroxy-L-DOPA was found to be the
      most sensitive donor. Picric acid, TNT, and RDX are analyzed with detection
      limits corresponding to 5.2 * 10(-12) M, 1.0 * 10(-12) M, and 3.0 * 10(-12) M,
      respectively, using the 6-hydroxy-L-DOPA-modified Ag NCs sensing module.

PMID- 25072886
TI  - Synthesis of N-functionalized/NH-multisubstituted indoles, thienopyrroles,
      pyrroloindoles, and pyrazolopyrroles via sequential one-pot base-mediated and
      copper-catalyzed inter- and intramolecular amination of 2-[2-bromo(het)aryl]-3
      (het)aryl-3-(methylthio)acrylonitriles.
AB  - A novel, efficient route to substituted 1-N-(het)aryl/NH-2-(het)aryl-3
      cyanoindoles and related pyrrolo-fused heterocycles such as thienopyrroles,
      pyrroloindoles, and pyrazolopyrroles has been reported. The overall protocol
      involves sequential cycloamination of readily available 2-[2-bromo(het)aryl]-3
      (het)aryl-3-(methylthio)acrylonitrile precursors with primary amines or amides
      via two key C-N bond-forming processes, one base-mediated intermolecular and the
      other Cu-catalyzed intramolecular arylamination leading to N(1)-C(2) and N(1)
      C(7a) bond formation, respectively, in a two-step one-pot procedure. 

PMID- 25072888
TI  - Interventions for treating femoral shaft fractures in children and adolescents.
AB  - BACKGROUND: Fractures of the femoral shaft in children are relatively uncommon
      but serious injuries that disrupt the lives of children and their carers and can
      result in significant long-term disability. Treatment involves either surgical
      fixation, such as intramedullary nailing or external fixation, or conservative
      treatment involving prolonged immobilisation, often in hospital. OBJECTIVES: To
      assess the effects (benefits and harms) of interventions for treating femoral
      shaft fractures in children and adolescents. SEARCH METHODS: We searched the
      Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (accessed 16
      August 2013), the Cochrane Central Register of Controlled Trials (The Cochrane
      Library 2013 Issue 7), MEDLINE (1946 to August Week 1 2013), EMBASE (1980 to 2012
      week 9), CINAHL (16 August 2013), clinical trials registries, conference
      proceedings and reference lists; and contacted trial authors and experts in the
      field. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials
      comparing conservative and surgical interventions for diaphyseal fractures of the
      femur in children under 18 years of age. Our primary outcomes were functional
      outcome measures, unacceptable malunion, and serious adverse events. DATA
      COLLECTION AND ANALYSIS: Two authors independently screened and selected trials,
      assessed risk of bias and extracted data. We assessed the overall quality of the
      evidence for each outcome for each comparison using the GRADE approach. We pooled
      data using a fixed-effect model. MAIN RESULTS: We included 10 trials (six
      randomised and four quasi-randomised) involving a total of 527 children (531
      fractures). All trials were at some risk of bias, including performance bias as
      care provider blinding was not practical, but to a differing extent. Just one
      trial was at low risk of selection bias. Reflecting both the risk of bias and the
      imprecision of findings, we judged the quality of evidence to be 'low' for most
      outcomes, meaning that we are unsure about the estimates of effect. Most trials
      failed to report on self-assessed function or when children resumed their usual
      activities. The trials evaluated 10 different comparisons, belonging to three
      main categories. Surgical versus conservative treatment Four trials presenting
      data for 264 children aged 4 to 12 years made this comparison. Low quality
      evidence (one trial, 101 children) showed children had very similar function
      assessed using the RAND health status score at two years after surgery (external
      fixation) compared with conservative treatment (spica cast): mean 69 versus 68.
      The other three trials did not report on function. There was moderate quality
      evidence (four trials, 264 children, aged 4 to 12 years, followed up 3 to 24
      months) that surgery reduced the risk of malunion (risk ratio (RR) 0.29, 95%
      confidence interval (CI) 0.15 to 0.59, 4 trials). Assuming an illustrative
      baseline risk of 115 malunions per 1000 in children treated conservatively, these
      data equate to 81 fewer (95% CI 47 to 97 fewer) malunions per 1000 in surgically
      treated children. Conversely, low quality evidence indicated that there were more
      serious adverse events such as infections after surgery (RR 2.39, 95% CI 1.10 to
      5.17, 4 trials). Assuming an illustrative baseline risk of 40 serious adverse
      events per 1000 for conservative treatment, these data equate to 56 more (95% CI
      4 to 167 more) serious adverse events per 1000 children treated surgically. There
      was low quality evidence (one trial, 101 children) of similar satisfaction levels
      in children and parents with surgery involving external fixation and plaster cast
      only. However, there was low quality evidence (one trial, 46 children) that more
      parents were satisfied with intramedullary nailing than with traction followed by
      a cast, and that surgery reduced the time taken off from school. Comparisons of
      different methods of conservative treatmentThe three trials in this category made
      three different comparisons. We are very unsure if unacceptable malunion rates
      differ between immediate hip spica versus skeletal traction followed by spica in
      children aged 3 to 10 years followed up for six to eight weeks (RR 4.0, 95% CI
      0.5 to 32.9; one trial, 42 children; very low quality evidence). Malunion rates
      at 5 to 10 years may not differ between traction followed by functional orthosis
      versus traction followed by spica cast in children aged 5 to 13 years (RR 0.98,
      95% CI 0.46 to 2.12; one trial, 43 children; low quality evidence). We are very
      unsure (very low quality evidence) if either function or serious adverse events
      (zero events reported) differ between single-leg versus double-leg spica casts
      (one trial, 52 young children aged two to seven years). Low quality evidence on
      the same comparison indicates that single-leg casts are less awkward to manage by
      parents, more comfortable for the child and may require less time off work by the
      caregiver. Comparisons of different methods of surgical treatmentThe three trials
      in this category made three different comparisons. Very low quality evidence
      means that we are very unsure if the rates of malunion, serious adverse events,
      time to return to school or parental satisfaction actually differ in children
      whose fractures were fixed using elastic stable intramedullary nailing or
      external fixation (one trial, 19 children). The same applies to the rates of
      serious adverse events and time to resume full weight-bearing in children treated
      with dynamic versus static external fixation (one trial, 52 children). Very low
      quality evidence (one trial, 47 children) means that we do not know if malunion,
      serious adverse events and time to resume weight-bearing actually differ between
      intramedullary nailing versus submuscular plating. However, there could be more
      difficulties in plate removal subsequently. AUTHORS' CONCLUSIONS: There is
      insufficient evidence to determine if long-term function differs between surgical
      and conservative treatment. Surgery results in lower rates of malunion in
      children aged 4 to 12 years, but may increase the risk of serious adverse events.
      Elastic stable intramedullary nailing may reduce recovery time.There is
      insufficient evidence from comparisons of different methods of conservative
      treatment or of different methods of surgical treatment to draw conclusions on
      the relative effects of the treatments compared in the included trials.

PMID- 25072887
TI  - Timely activation of budding yeast APCCdh1 involves degradation of its inhibitor,
      Acm1, by an unconventional proteolytic mechanism.
AB  - Regulated proteolysis mediated by the ubiquitin proteasome system is a
      fundamental and essential feature of the eukaryotic cell division cycle. Most
      proteins with cell cycle-regulated stability are targeted for degradation by one
      of two related ubiquitin ligases, the Skp1-cullin-F box protein (SCF) complex or
      the anaphase-promoting complex (APC). Here we describe an unconventional cell
      cycle-regulated proteolytic mechanism that acts on the Acm1 protein, an inhibitor
      of the APC activator Cdh1 in budding yeast. Although Acm1 can be recognized as a
      substrate by the Cdc20-activated APC (APCCdc20) in anaphase, APCCdc20 is neither
      necessary nor sufficient for complete Acm1 degradation at the end of mitosis. An
      APC-independent, but 26S proteasome-dependent, mechanism is sufficient for
      complete Acm1 clearance from late mitotic and G1 cells. Surprisingly, this
      mechanism appears distinct from the canonical ubiquitin targeting pathway,
      exhibiting several features of ubiquitin-independent proteasomal degradation. For
      example, Acm1 degradation in G1 requires neither lysine residues in Acm1 nor
      assembly of polyubiquitin chains. Acm1 was stabilized though by conditional
      inactivation of the ubiquitin activating enzyme Uba1, implying some requirement
      for the ubiquitin pathway, either direct or indirect. We identified an amino
      terminal predicted disordered region in Acm1 that contributes to its proteolysis
      in G1. Although ubiquitin-independent proteasome substrates have been described,
      Acm1 appears unique in that its sensitivity to this mechanism is strictly cell
      cycle-regulated via cyclin-dependent kinase (Cdk) phosphorylation. As a result,
      Acm1 expression is limited to the cell cycle window in which Cdk is active. We
      provide evidence that failure to eliminate Acm1 impairs activation of APCCdh1 at
      mitotic exit, justifying its strict regulation by cell cycle-dependent
      transcription and proteolytic mechanisms. Importantly, our results reveal that
      strict cell-cycle expression profiles can be established independent of
      proteolysis mediated by the APC and SCF enzymes. 

PMID- 25072890
TI  - Physical, lifestyle, psychological, and social determinants of pain intensity,
      pain disability, and the number of pain locations in depressed older adults.
AB  - Late-life depression and pain more often co-occur than can be explained by
      chance. Determinants of pain in late-life depression are unknown, even though
      knowledge on possible determinants of pain in depression is important for
      clinical practice. Therefore, the objectives of the present study were 1) to
      describe pain characteristics of depressed older adults and a nondepressed
      comparison group, and 2) to explore physical, lifestyle, psychological, and
      social determinants of acute and chronic pain intensity, disability, and
      multisite pain in depressed older adults. Data from the Netherlands Study of
      Depression in Older Persons cohort, consisting of 378 depressed persons,
      diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition criteria, and 132 nondepressed persons aged 60 years and older, were used
      in a cross-sectional design. Pain characteristics were measured by the Chronic
      Graded Pain Scale. Multiple linear regression analyses were performed to explore
      the contribution of physical, lifestyle, psychological, and social determinants
      to outcomes pain intensity, disability, and the number of pain locations.
      Depressed older adults more often reported chronic pain and experienced their
      pain as more intense and disabling compared to nondepressed older adults.
      Adjusted for demographic, physical, and lifestyle characteristics, multinomial
      logistic regression analyses showed increased odds ratios (OR) for depression in
      acute pain (OR 3.010; P=0.005) and chronic pain (OR 4.544, P<0.001). In addition,
      linear regression analyses showed that acute and chronic pain intensity,
      disability, and multisite pain were associated with several biopsychosocial
      determinants, of which anxiety was most pronounced. Further research could focus
      on the temporal relationship between anxiety, late-life depression, and pain.

PMID- 25072891
TI  - Expression of the androgen receptor in the testes and the concentrations of
      gonadotropins and sex steroid hormones in male turkeys (Meleagris gallopavo)
      during growth and development.
AB  - Androgens, including testosterone (T) and androstenedione (A4), are essential for
      puberty, fertility and sexual functions. The biological activity of those
      hormones is mediated via the androgen receptor (AR). The regulation of androgen
      action in birds is poorly understood. Therefore, the present study analysed mRNA
      and protein expression of AR in the testes, plasma concentrations of the
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), T, A4 and
      oestradiol (E2), as well as the levels of T, A4 and E2 in testicular homogenates
      of male turkeys (Meleagris gallopavo) at the age of 4, 8, 12, 16, 20, 24 and
      28weeks. Plasma concentrations of LH and FSH, as well as plasma and testicular
      levels of T and A4 began to increase at 20weeks of age. The lowest plasma levels
      of E2 were noted at 20weeks relative to other growth stages. The 20th week of
      life seems to be the key phase in the development of the reproductive system of
      turkeys. The AR protein was found in the nuclei of testicular cells in all
      examined growth stages. Higher expression of AR protein in the testes beginning
      at 20weeks of age was accompanied by high plasma concentrations of LH and high
      plasma and testicular levels of androgens. This relationship seems to be
      necessary to regulate male sexual function. 

PMID- 25072892
TI  - Metabolomic, behavioral, and reproductive effects of the aromatase inhibitor
      fadrozole hydrochloride on the unionid mussel Lampsilis fasciola.
AB  - Androgen-induced masculinization of female aquatic biota poses concerns for
      natural population stability. This research evaluated the effects of a twelve day
      exposure of fadrozole hydrochloride on the metabolism and reproductive status of
      the unionid mussel Lampsilis fasciola. Although this compound is not considered
      to be widespread in the aquatic environment, it was selected as a model aromatase
      (enzyme that converts testosterone to estradiol) inhibitor. Adult mussels were
      exposed to a control and 3 concentrations of fadrozole (2MUg/L, 20MUg/L, and
      50MUg/L), and samples of gill tissue were taken on days 4 and 12 for metabolomics
      analysis. Gills were used because of the variety of critical processes they
      mediate, such as feeding, ion exchange, and siphoning. Daily observed mussel
      behavior included female mantle display, foot protrusion, siphoning, and larval
      (glochidia) releases. Glochidia mortality was significantly higher in the 20MUg/L
      treatment. Fewer conglutinate (packets of glochidia) releases were observed in
      the 50MUg/L treatment, and mortality was highly correlated to release numbers.
      Foot protrusion was significantly higher in females in nearly all treatments,
      including the control, during the first 4days of observations. However, this sex
      difference was observed only in the 50MUg/L treatment during the last 8days.
      Generally, metabolites were significantly altered in female gill tissue in the
      2MUg/L treatment whereas males were mostly affected only at the highest (50MUg/L)
      treatment. Both sexes also revealed significant reductions in fadrozole-induced
      metabolic effects in gill tissue sampled after 12days compared to tissue sampled
      after 4days, indicating time-dependent mechanisms of disruptions in metabolic
      pathways and homeostatic processes to compensate for such disruptions. 

PMID- 25072893
TI  - Cadmium in placenta- a valuable biomarker of exposure during pregnancy in
      biomedical research.
AB  - Rats were exposed to cadmium (Cd) during pregnancy orally (50 ppm Cd in drinking
      water from gestation day [GD] 1-20) or parenterally (5 mg/kg sc during GD 1-19 or
      on GD 16). Cadmium levels were measured in blood, placenta, and fetus at the end
      of exposure. Human studies comprised of two cohorts of healthy Croatian
      postpartum women in the continental versus coastal area; in these women, Cd
      levels were measured in maternal blood, placenta, and cord blood. Cadmium in rat
      placenta was 10-fold higher following parenteral versus oral exposure, with
      highest value after exposure in mid pregnancy. The values were 10-fold higher in
      placenta than blood, and the fetus had <=10% of blood metal levels. Cadmium
      levels in human placenta noted increased values in smokers that were 10- to 20
      fold higher than in maternal blood and in cord blood were very low (<0.1 ppb). In
      nonsmokers, different Cd levels in placenta and blood in coastal versus
      continental area were found due to dietary intake. Data showed that Cd in
      placenta is a reliable biomarker of exposure following oral and parenteral
      treatment during pregnancy in rats and in human biomonitoring that includes
      prenatal assessment. In addition, tobacco smoking is a prominent source of metal
      exposure. Cd levels in placenta are also a valuable biomarker of metal dietary
      exposure related to specific dietary habits and soil characteristics. 

PMID- 25072894
TI  - Fine particulate air pollution and hospital admissions for asthma: a case
      crossover study in Taipei.
AB  - This study was undertaken to determine whether there was a correlation between
      fine particles (PM2.5) levels and hospital admissions for asthma in Taipei,
      Taiwan. Hospital admissions for asthma and ambient air pollution data for Taipei
      were obtained for the period of 2006-2010. The relative risk of hospital
      admissions for asthma was estimated using a case-crossover approach, controlling
      for weather variables, day of the week, seasonality, and long-term time trends.
      For the single-pollutant model (without adjustment for other pollutants),
      increased asthma admissions were significantly associated with PM2.5 levels both
      on warm days (>23 degrees C) and cool days (<23 degrees C), with an interquartile
      range rise associated with a 12% (95% CI = 6-18%) and 3% (95% CI = 0-8%)
      elevation in admissions for asthma, respectively. In the two-pollutant models,
      PM2.5 levels remained significant for increased asthma admissions after inclusion
      of SO2 or O3 both on warm and cool days. This study provides evidence that higher
      levels of PM2.5 elevate the risk of hospital admissions for asthma in Taiwan. 

PMID- 25072895
TI  - Lead in shrimp Litopenaeus vannamei Boone in sublethal concentrations.
AB  - Determination of the accumulation and elimination of sublethal lead (Pb) in
      different shrimp tissues may be useful as an indicator of uptake and elimination
      characteristics of this metal. Aquaculture ponds are particularly influenced by
      Pb contamination, where aquatic animals may acquire the metal through adsorption
      to exoskeletons or gills from the surrounding water. Cationic Pb is accumulated
      preferentially in the nonedible fraction of shrimp, followed by exoskeleton, and
      to a minor extent in muscle. Lead contents in different tissues were lower than
      metal levels in exoskeleton. However, the presence of Pb in sediment due to
      purging may exert adverse consequences on shrimp as bottom feeders. 

PMID- 25072896
TI  - Short-term effects of fine particulate air pollution on hospital admissions for
      respiratory diseases: a case-crossover study in a tropical city.
AB  - This study was undertaken to determine whether there was a correlation between
      fine particles (PM2.5) levels and hospital admissions for respiratory diseases in
      Kaohsiung, Taiwan. Hospital admissions for respiratory diseases including
      pneumonia, asthma, and chronic obstructive pulmonary disease (COPD) and ambient
      air pollution data for Kaohsiung were obtained for the period 2006-2010. The
      relative risk (RR) of hospital admissions for respiratory diseases was estimated
      using a case-crossover approach, controlling for weather variables, day of the
      week, seasonality, and chronic time trends. For the single-pollutant model
      (without adjustment for other pollutants), increased number of admissions for
      respiratory diseases were significantly associated with higher PM2.5 levels only
      on cool days (<25 degrees C), with an interquartile range rise associated with a
      50 (95% CI% = 45-55%), 40% (95% CI = 25-58%), and 46% (95% CI = 36-57%) elevation
      in frequency of admissions for pneumonia, asthma, and COPD, respectively. In the
      two-pollutant models, PM2.5 levels remained significant even controlling for
      sulfur dioxide, nitrogen dioxide, carbon monoxide, or ozone on cool days. This
      study provides evidence that higher levels of PM2.5 increase the risk of hospital
      admissions for respiratory diseases in Taiwan. 

PMID- 25072897
TI  - Effects on five species of shorebirds of experimental closure of a beach in New
      Jersey: implications for severe storms and sea-level rise.
AB  - For management, it is important to understand the factors that affect foraging
      efficiency of birds during migration, especially in the face of severe storms and
      sea-level rise. An experiment was conducted whereby a beach used extensively by
      migrant shorebirds and people was open and experimentally closed to human
      activity to examine factors affecting feeding when there was no disturbance, with
      the beach opened or closed to human activity, and following disturbances. When
      the beach was closed, the factors affecting the percent of shorebirds foraging
      varied by species, but involved the number of conspecifics or other shorebirds,
      location along the beach, and number of raptors. Overall, 30% of flocks were
      disturbed as a function of type of disturbance, location along the beach, and
      whether the beach was open or closed. These data suggest that individuals,
      vehicles, and raptors influence the ability of shorebirds to forage undisturbed,
      indicating the importance of having some sections of important stopover beaches
      where shorebirds can feed and roost undisturbed by human activity. A corollary is
      that other parts of the beach can be freely used by people; environmental health
      can encompass both protected areas for shorebirds and open areas for fishing and
      recreation. Severe storms and sea-level rise will limit beach space for both
      human and avian activities, and understanding mitigation for both is essential to
      wise adaptive management. 

PMID- 25072898
TI  - Evaluating an alternative method for rapid urinary creatinine determination.
AB  - Creatinine (CR) is an endogenously produced chemical that is routinely assayed in
      urine specimens to assess kidney function and sample dilution. The industry
      standard method for CR determination, known as the kinetic Jaffe (KJ) method,
      relies on an exponential rate of a colorimetric change, and can therefore require
      automated processing equipment for moderate- to high-throughput analysis
      (hundreds to thousands of samples per day). This study evaluates an alternative
      colorimetric method, the "plateau Jaffe" (PJ) method, which utilizes the
      chemistry of the KJ method, a commercially available kit, and a multipoint
      calibration curve. This method is amenable to moderate-throughput sample analysis
      and does not require automated processing equipment. Thirty-two spot urine
      samples from healthy adult volunteers were analyzed for creatinine concentration
      (CRc) using the KJ and PJ methods. Samples were also analyzed using a liquid
      chromatography time-of-flight mass spectrometry (LC-TOF/MS) method, which acted
      as an analytical control. Replicate measurements of spot samples (natural log
      transformed values) were used to estimate method precision, and linear regression
      models were used to evaluate method accuracy (LC-TOF/MS measurements were
      considered the analytical benchmark). Measurement precision was comparable across
      all three methods, with coefficent of variation estimates ranging from 3 to 6%.
      Regression models generally showed good agreement across methods with R(2)
      estimates ranging from .996 to .998, slope estimates ranging from .944 to .986,
      and y-intercept estimates ranging from 0.111 to 0.303. Minor bias (between 2 and
      16%) was observed across methods at the tails of the measurement distributions.
      The provided regression equations can be used to adjust for this bias and to
      improve CR measurement comparisons across studies employing different methods.
      Considering these results, the PJ method is a suitable alternative to the
      industry standard KJ method for urinary CRc determination. It can be implemented
      for moderate-throughput sample analysis using modest and commonly available lab
      instrumentation and manual sample preparation techniques. 

PMID- 25072899
TI  - Ab initio X(1)0(+) ground state potential curves of Pb...RG dimers (RG = He, Ne,
      Ar) including spin-orbit effects. Simulation of diffusion coefficients.
AB  - CCSD(T) ground state potential curves of Pb...RG systems (RG = He, Ne and Ar) are
      presented and the importance of the inclusion of spin-orbit effects is discussed.
      The closed-shell character of the Pb atom at the two-component relativistic level
      of relativistic theory leads to shallower potential energy curves compared to
      scalar relativistic open-shell calculations. The pressure-independent cross
      diffusion coefficients pD12 have been simulated using the extrapolated two
      component CCSD(T) ground state potential curves. The diffusion coefficients from
      scattering theory are compared with simulations based on molecular dynamics (MD)
      using the velocity autocorrelation function (VACF) and the Einstein equation. A
      correction for the proper assessment of the uncertainty in the VACF is proposed.
      The acceleration of the MD simulation of Pb in RG diffusion is proposed utilizing
      the RG in Pb diffusion. The dU[TQ]Z/CCSD(T) potential curve of Pb...He (De =
      8.667 cm(-1), re = 4.683 A) supports only one vibrational level. The
      anharmonicity of this potential is compared to the potential of He...He which
      also supports only one vibrational level. The comparison is based on the mean
      square separations of the vibrational wave function.

PMID- 25072900
TI  - A proprioceptive ability factor underlying all proprioception tests? Response to
      Tremblay (2013).
AB  - There may be a higher-order processing system (or general proprioceptive ability)
      which receives inputs from various proprioceptive sources across different body
      areas. In general, Tremblay's (2013 ) criticisms are overly based on peripheral
      proprioceptors, and do not represent alternative interpretations or the data
      generated by studies evaluating those interpretations.

PMID- 25072901
TI  - Seeing reversals in ambiguous images: to know or not to know?
AB  - The present study is an attempt to replicate the 1992 findings of Rock and
      Mitchener that knowing about the ambiguity in ambiguous images is necessary for
      seeing reversals. In contrast to Rock and Mitchener's study, the present study
      used a between-subjects design, in which 190 participants were randomly assigned
      to either an uninformed or an informed condition, and saw 12 images, 6 ambiguous
      and 6 unambiguous. The findings show that participants in the informed condition
      were significantly more likely to see reversals in the ambiguous images than were
      those in the uninformed condition. In contrast to Rock and Mitchener's findings,
      knowledge of ambiguity did not ensure that all informed participants saw all six
      reversals; there were spontaneous reversals in the uninformed condition for most
      of the images. These findings are discussed in terms of suggesting that seeing a
      reversal in an ambiguous image is a complex process that requires consideration
      of the interplay of visual perception and higher order cognition.

PMID- 25072902
TI  - A wavelet approach to detect enriched regions and explore epigenomic landscapes.
AB  - Epigenetic landscapes represent how cells regulate gene activity. To understand
      their effect on gene regulation, it is important to detect their occupancy in the
      genome. Unlike transcription factors whose binding regions are limited to narrow
      regions, histone modification marks are enriched over broader areas. The
      stochastic characteristics unique to each mark make it hard to detect their
      enrichment. Classically, a predefined window has been used to detect their
      enrichment. However, these approaches heavily rely on the predetermined
      parameters. Also, the window-based approaches cannot handle the enrichment of
      multiple marks. We propose a novel algorithm, called SeqW, to detect enrichment
      of multiple histone modification marks. SeqW applies a zooming approach to detect
      a broadly enriched domain. The zooming approach helps domain detection by
      increasing signal-to-noise ratio. The borders of the domains are detected by
      studying the characteristics of signals in the wavelet domain. We show that SeqW
      outperformed previous predictors in detecting broad peaks. Also, we applied SeqW
      in studying spatial combinations of histone modification patterns.

PMID- 25072903
TI  - In situ sample processing approach (iSPA) for comprehensive quantitative
      phosphoproteome analysis.
AB  - Current sample preparation protocols for quantitative phosphoproteome analysis
      are tedious and time-consuming. Here, a facile in situ sample processing approach
      (iSPA) is developed by using macroporous Ti(IV)-IMAC microspheres as the
      preparation "beds", where all sample preparation procedures including the
      enrichment of phosphoproteins, tryptic digestion of proteins, enrichment, and
      isotope labeling of phosphopeptides are performed in situ sequentially. As a
      result of the in situ processing design and the seamless procedures, extra steps
      for desalting and buffer exchanging, which are always required in conventional
      approaches, are avoided, and the sample loss and contamination could be greatly
      reduced. Thus, better sensitivity and accuracy for the quantitative
      phosphoproteome analysis were obtained. This strategy was further applied to
      differential phosphoproteome analysis of human liver tissues with or without
      hepatocellular carcinoma (HCC). In total, 8548 phosphorylation sites were
      confidently quantified from three replicate analyses of 0.5 mg of human liver
      protein extracts. 

PMID- 25072904
TI  - Surgery. beta-Blockers--still a trusted ally or time for retirement?
AB  - Uncertainty surrounds the benefit of beta-blocker treatment in various clinical
      settings. The researchers in a new retrospective analysis of preoperative beta
      blocker use in CABG surgery now add to the debate, and suggest that these drugs
      might not improve perioperative outcomes.

PMID- 25072905
TI  - Explanations for the 'smoker's paradox' in cardiac resuscitation.

PMID- 25072906
TI  - Atrial fibrillation. Cryptogenic stroke--can we abandon this apologetic
      diagnosis?
AB  - Cryptogenic stroke is an apology for ignorance about the cause of ischaemic
      stroke. Now, in two new studies involving long-term electrocardiogram monitoring,
      investigators from the EMBRACE and CRYSTAL-AF trials suggest that many instances
      of cryptogenic stroke might be caused by undetected atrial fibrillation.

PMID- 25072907
TI  - Risk factors. Reducing alcohol intake improves heart health.

PMID- 25072908
TI  - Dyslipidaemia. Fasting before blood lipid testing might be unnecessary.

PMID- 25072909
TI  - Hypertension. Age-specificity of blood-pressure-associated complications.
AB  - In an analysis of electronic health records, 1.25 million patients aged >=30
      years without diagnosed cardiovascular disease experienced 83,098 cardiovascular
      events during follow-up (median 5.2 years). Associations between incident
      cardiovascular disease and blood pressure differed for systolic and diastolic
      blood pressures and between the 12 cardiovascular end points examined.

PMID- 25072911
TI  - Coronary artery disease. Detection of ischaemic heart disease in symptomatic
      women.
AB  - The 2014 revision of the 2005 AHA consensus statement on the evaluation of women
      with suspected ischaemic heart disease is a major update. The authors discuss the
      spectrum of ischaemic heart disease and review new data on the diagnostic and
      prognostic performance of the various diagnostic testing modalities now
      available.

PMID- 25072912
TI  - Arrhythmias. Cardiac resynchronization therapy in women.
AB  - A meta-analysis by investigators from FDA of three major trials of cardiac
      resynchronization therapy (CRT) demonstrated that women have a reduced rate of
      heart failure (HF) and death with CRT at a shorter QRS duration than men.
      Recognizing these sex-specific differences is important to improve outcomes for
      women with HF.

PMID- 25072910
TI  - Constrictive pericarditis--a curable diastolic heart failure.
AB  - Constrictive pericarditis can result from a stiff pericardium that prevents
      satisfactory diastolic filling. The distinction between constrictive pericarditis
      and other causes of heart failure, such as restrictive cardiomyopathy, is
      important because pericardiectomy can cure constrictive pericarditis. Diagnosis
      of constrictive pericarditis is based on characteristic haemodynamic and
      anatomical features determined using echocardiography, cardiac catheterization,
      cardiac MRI, and CT. The Mayo Clinic echocardiography and cardiac catheterization
      haemodynamic diagnostic criteria for constrictive pericarditis are based on the
      unique features of ventricular interdependence and dissociation of intrathoracic
      and intracardiac pressures seen when the pericardium is constricted. A complete
      pericardiectomy can restore satisfactory diastolic filling by removing the
      constrictive pericardium in patients with constrictive pericarditis. However, if
      inflammation of the pericardium is the predominant constrictive mechanism, anti
      inflammatory therapy might alleviate this transient condition without a need for
      surgery. Early diagnosis of constrictive pericarditis is, therefore, of paramount
      clinical importance. An improved understanding of how constrictive pericarditis
      develops after an initiating event is critical to prevent this diastolic heart
      failure. In this Review, we discuss the aetiology, pathophysiology, and diagnosis
      of constrictive pericarditis, with a specific emphasis on how to differentiate
      this disease from conditions with similar clinical presentations. 

PMID- 25072913
TI  - Heart failure. BMD a predictor of incident heart failure.

PMID- 25072915
TI  - Improvements in teaching behavior at two German medical schools resulting from a
      modified Flanders interaction analysis feedback intervention process.
AB  - Abstract Background: Person-centered teachers who are more empathic and
      "indirect" (accept, encourage, praise and ask questions) tend to be more
      effective than those who are "direct" (lecture, give directions and criticize)
      (Amidon & Flanders 1991). The Flanders Interaction Analysis (FIA) is a tool for
      diagnosing these teaching aspects, though not yet used to improve lecturing in
      undergraduate medical education. AIMS: Does structured expert feedback to
      volunteer lecturers lead to improvement in person-centered teaching behavior as
      measured by a Modified Flanders Interaction Analysis (MFIA) and student
      questionnaires? METHODS: Twenty-one volunteer lecturers from two German medical
      faculties were stratified by past teaching experience and randomized into two
      groups. The intervention group received MFIA diagnoses of their lectures plus
      feedback by an expert observer after winter and summer semester lectures,
      respectively. The control group was only diagnosed with the MFIA. Teaching
      behavior changes for both groups were compared and teacher feedback about the
      intervention process was assessed. RESULTS: Faculty in the intervention group
      improved significantly in their summer lectures regarding person-centered
      teaching behavior while controls did not. CONCLUSIONS: A structured individual
      expert feedback intervention using a MFIA as a teaching diagnostic tool is a
      powerful, cost-effective faculty development process for improving teaching
      behavior of volunteer lecturers in undergraduate medical education.

PMID- 25072917
TI  - Electronic properties of self-assembled trimesic acid monolayer on graphene.
AB  - The adsorption of trimesic acid (TMA) on a graphene surface has been studied with
      density functional theory. By considering the adsorption of a single TMA molecule
      on different sites on graphene, we have been able to perform a detailed analysis
      of the equilibrium geometry, charge transfer, electronic properties in terms of
      density of states and band structure, and finally scanning tunneling microscopy
      simulations on those simple systems. The results for isolated adsorption were
      then compared to the behavior of the TMA unit within two different self-assembled
      monolayers. Our results indicate that structural deformations of TMA may
      significantly contribute to the magnitude of p-doping and band gap opening in
      graphene. The formation of a hydrogen bonding network within the assembly
      improves the stability of the adlayer, but its adhesion on graphene is
      significantly reduced. The magnitude of p-doping in graphene per TMA unit remains
      nearly constant from the isolated to the assembled systems, but the magnitude of
      the band gap opening appears to be strongly correlated with the breaking of
      symmetry of pi-states of graphene by the TMA patterning on the surface. Our
      results suggest that polymorphism in self-assembled adlayers could be used to
      tune and control the electronic properties of graphene. 

PMID- 25072914
TI  - KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion
      injury.
AB  - Mitochondrial potassium channels have been implicated in myocardial protection
      mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage
      activated potassium channel of big-conductance (BK) have a pre-conditioning-like
      effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently,
      mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct
      limiting factors that derive directly from the KCNMA1 gene encoding for canonical
      BKs usually present at the plasma membrane of cells. However, some studies
      challenged these cardio-protective roles of mitoBKs. Herein, we present
      electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated
      currents of 190 pS conductance in mitoplasts from wild-type but not BK-/-
      cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles
      fibres showed normal ultra-structures and matrix dimension, but oxidative
      phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were
      significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of
      BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte
      mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at
      hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for
      oxidative metabolism are important determinants of cellular survival, we tested
      BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R)
      injury. Infarct areas, coronary flow and heart rates were not different between
      wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre
      conditioning (IP), but differed upon IP. While the area of infarction comprised
      28+/-3% of the area at risk in wild-type, it was increased to 58+/-5% in BK-/-
      hearts suggesting that BK mediates the beneficial effects of IP. These findings
      suggest that cardiac BK channels are important for proper oxidative energy supply
      of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and
      that IP might indeed favor survival of the myocardium upon I/R injury in a BK
      dependent mode stemming from both mitochondrial post-anoxic ROS modulation and
      non-mitochondrial localizations. 

PMID- 25072916
TI  - High-glucose-induced CARM1 expression regulates apoptosis of human retinal
      pigment epithelial cells via histone 3 arginine 17 dimethylation: role in
      diabetic retinopathy.
AB  - Hyperglycemia-induced apoptosis of retinal pigment epithelial (RPE) cells is
      considered to be involved in the progression of diabetic retinopathy. Histone
      arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has
      emerged as an important histone modification involved in gene regulation.
      However, the role of PRMTs in diabetic retinopathy has not been elucidated. Here,
      we found that expression of coactivator-associated arginine methyltransferase 1
      (CARM1; also known as PRMT4) was increased in the high-glucose treated human RPE
      cell line ARPE-19 and in the RPE layer of streptozotocin-treated rats. In
      addition, high-glucose induced apoptosis in ARPE-19 cells. To determine the
      function of CARM1 on RPE cell apoptosis, we performed gain- and loss-of-function
      studies. CARM1 overexpression increased apoptosis of RPE cells. In contrast,
      silencing of CARM1 expression by siRNA and pharmacological inhibition of CARM1
      activity abolished high-glucose-induced RPE cell apoptosis. Furthermore, we found
      that inhibition of histone 3 arginine 17 (H3R17) asymmetric dimethylation
      attenuates both CARM1- and high-glucose-induced apoptosis in RPE cells. Together,
      these results show that high-glucose-induced CARM1 expression increases RPE cell
      apoptosis via H3R17 asymmetric dimethylation. Strategies to reduce CARM1
      expression or enzymatic activity could be used to prevent apoptosis of RPE cells
      in the progression of diabetic retinopathy. 

PMID- 25072918
TI  - Metabolic flux pattern of glucose utilization by Xanthomonas campestris pv.
      campestris: prevalent role of the Entner-Doudoroff pathway and minor fluxes
      through the pentose phosphate pathway and glycolysis.
AB  - The well-studied plant pathogenic bacterium Xanthomonas campestris pv. campestris
      (Xcc) synthesizes the biotechnologically important polysaccharide xanthan gum,
      which is also regarded as a virulence factor in plant interactions. In Xcc,
      sugars like glucose are utilized as a source to generate energy and biomass for
      growth and pathogenicity. In this study, we used [1-(13)C]glucose as a tracer to
      analyze the fluxes in the central metabolism of the bacterium growing in a
      minimal medium. (13)C-Metabolic flux analysis based on gas chromatography-mass
      spectrometry (GC-MS) confirmed the prevalent catabolic role of the Entner
      Doudoroff pathway. Comparative nuclear magnetic resonance (NMR)-based
      isotopologue profiling of a mutant deficient in glycolysis gave evidence for a
      moderate flux via glycolysis in the wild-type. In addition to reconfirming the
      Entner-Doudoroff pathway as a catabolic main route, this approach affirmed a
      numerically minor but important flux via the pentose phosphate pathway. 

PMID- 25072919
TI  - Importance of freeze-thaw events in low temperature ecotoxicology of cold
      tolerant enchytraeids.
AB  - Due to global warming it is predicted that freeze-thaw cycles will increase in
      Arctic and cold temperate regions. The effects of this variation becomes of
      particular ecological importance to freeze-tolerant species when it is combined
      with chemical pollutants. We compared the effect of control temperature (2 
      degrees C), daily freeze-thaw cycles (2 to -4  degrees C) and constant freezing (
      2  degrees C) temperatures on the cold-tolerance of oligochaete worms
      (Enchytraeus albidus) and tested how survival was influenced by pre-exposure to 4
      nonylphenol (4-NP), a common nonionic detergent found in sewage sludge amended
      soils. Results showed that combined effect of 4-NP and daily freeze-thaw cycles
      can cause higher mortality to worms as compared with sustained freezing or
      control temperature. Exposure to 4-NP caused a substantial depletion of glycogen
      reserves which is catabolized during freezing to produce cryoprotective
      concentrations of free glucose. Further, exposure to freeze-thaw cycles resulted
      in higher concentrations of 4-NP in worm tissues as compared to constant freezing
      or control temperature (2  degrees C). Thus, worms exposed to combined effect of
      freeze-thaw cycles and 4-NP suffer higher consequences, with the toxic effect of
      the chemical potentiating the deleterious effects of freezing and thawing.

PMID- 25072920
TI  - Improved production of alpha-ketoglutaric acid (alpha-KG) by a Bacillus subtilis
      whole-cell biocatalyst via engineering of L-amino acid deaminase and deletion of
      the alpha-KG utilization pathway.
AB  - We previously developed a novel one-step biotransformation process for the
      production of alpha-ketoglutarate (alpha-KG) from L-glutamic acid by a Bacillus
      subtilis whole-cell biocatalyst expressing an L-amino acid deaminase (pm1) of
      Proteus mirabilis. However, the biotransformation efficiency of this process was
      low owing to low substrate specificity and high alpha-KG degradation. In this
      study, we further improved alpha-KG production by protein engineering P.
      mirabilis pm1 and deleting the B. subtilis alpha-KG degradation pathway. We first
      performed three rounds of error-prone polymerase chain reaction and identified
      mutations at six sites (F110, A255, E349, R228, T249, and I352) that influence
      catalytic efficiency. We then performed site-saturation mutagenesis at these
      sites, and the mutant F110I/A255T/E349D/R228C/T249S/I352A increased the
      biotransformation ratio of L-glutamic acid from 31% to 83.25% and the alpha-KG
      titer from 4.65 g/L to 10.08 g/L. Next, the reaction kinetics and biochemical
      properties of the mutant were analyzed. The Michaelis constant for L-glutamic
      acid decreased from 49.21 mM to 23.58 mM, and the maximum rate of alpha-KG
      production increased from 22.82 MUM min(-1) to 56.7 MUM min(-1). Finally, the
      sucA gene, encoding alpha-ketodehydrogenase, was deleted to reduce alpha-KG
      degradation, increasing the alpha-KG titer from 10.08 g/L to 12.21 g/L. Protein
      engineering of P. mirabilis pm1 and deletion of the alpha-KG degradation pathway
      in B. subtilis improved alpha-KG production over that of previously developed
      processes.

PMID- 25072921
TI  - Changes in plasma concentrations of progesterone, dehydroepiandrosterone and
      corticosterone in response to acute stress of capture, handling and restraint in
      two subspecies of white-crowned sparrows.
AB  - The aim of this study was to determine circulating patterns of the three major
      adrenal steroids in blood in response to stress during acute restraint handling
      in two subspecies of white-crowned sparrow. Gambel's white-crowned sparrows
      (Zonotrichia leucophrys gambelii) are long distance migrants that breed at high
      latitudes and Nuttall's white-crowned sparrows (Zonotrichia leucophrys nuttalli)
      are residents of coastal California. Column partition chromatography was
      developed to separate progesterone, dehydroepiandrosterone (DHEA), and
      corticosterone from a small plasma sample. Each of these steroids has the
      capability to modulate the stress response through various mechanisms. For
      example, progesterone is bound to corticosterone binding globulin (CBG) with a
      higher affinity than corticosterone. If plasma levels of progesterone rise during
      acute stress, then this could displace corticosterone from CBG and increase the
      amount of biologically active, free, corticosterone in blood.
      Dehydroepiandrosterone (DHEA) has been implicated to have many anti-stress
      properties with the potential to mitigate some of the actions of corticosterone.
      Results indicate that progesterone levels in both subspecies are elevated in
      response to acute stress handling. DHEA levels declined in Gambel's but did not
      change in Nuttall's. Thus DHEA does not follow the same secretory pattern as in
      mammals. Corticosterone levels were elevated in response to acute stress handling
      in both subspecies. This study provides new insight into an integrated stress
      response among three steroids. 

PMID- 25072922
TI  - Point mutagenesis reveals that a coiled-coil motif of CrV1 is required for entry
      to hemocytes to suppress cellular immune responses.
AB  - Various immunosuppressive factors are derived from polydnaviruses (PDVs) mutually
      symbiotic to some ichneumonid and braconid wasps. CrV1 was originally identified
      from a PDV called Cotesia rubecula bracovirus. CrV1 orthologs are reported in
      other Cotesia-associated PDVs, but not clearly understood in their physiological
      functions. This study determined a function of CrV1 encoded in Cotesia plutellae
      bracovirus (CpBV). CpBV-CrV1 is the largest molecule among the known CrV1s and is
      predicted to possess three coiled-coil motifs. It was constitutively expressed in
      parasitized host, Plutella xylostella. In vivo transient expression of CpBV-CrV1
      significantly impaired hemocyte nodule formation. However, its specific RNA
      interference significantly recovered the immune response. Two point mutations
      (Ala->Pro at 192nd and 196th positions) were designed to remove the main coiled
      coil motif of CpBV-CrV1. When CpBV-CrV1 and the mutant CpBV-CrV1 were expressed
      in Sf9 cells, their proteins were synthesized and secreted into each culture
      medium. When each culture medium was overlaid on hemocytes of nonparasitized P.
      xylostella, an immunofluorescence assay showed that CpBV-CrV1 entered the
      hemocytes, but the mutant protein did not. The entered CpBV-CrV1 significantly
      inhibited hemocyte-spreading behavior by preventing F-actin formation. These
      results indicate that CpBV-CrV1 is an immunosuppressive factor of CpBV, in which
      its coiled-coil motif is essential. 

PMID- 25072923
TI  - Altered innervation of the fallopian tube in ectopic pregnancy.
AB  - Three cases of ectopic pregnancy demonstrate different patterns of abnormal
      innervation in the fallopian tube. In the isthmus of the fallopian tube, we
      observed either (1) loss of nerves in one or more muscle layers of the fallopian
      tube or (2) large numbers of abnormal nerve profiles in one or more layers of
      muscle of the fallopian tube. Each woman had a prior history of one or more
      surgical terminations of pregnancy at indeterminate gestational ages. A
      proportion of uterine and tubal nerves pass through the uterosacral ligaments to
      reach the endometrial-myometrial nerve plexus and terminate as the innervation to
      the ipsilateral fallopian tube. We propose that injuries to the uterosacral
      ligaments by excessive traction to the cervix, or over-vigorous curettage to the
      endometrial-myometrial nerve plexus may account for these neuro
      immunohistochemical findings. There were no signs of chronic infection or
      inflammation in the fallopian tube in any of these cases. 

PMID- 25072924
TI  - Caesarean scar pregnancy complicated by placenta percreta followed by suppurative
      appendicitis after conservative management with methotrexate.

PMID- 25072925
TI  - Demonstration of cerebrospinal fluid leakage on radionuclide cisternography by
      SPECT/CT.
AB  - We report a case of a 37-year-old woman with severe headache provoked by postural
      changes who was referred to the nuclear medicine department for radionuclide
      cisternography to demonstrate suspected cerebrospinal fluid leakage. There was an
      increased uptake laterally on the left paraspinal region of upper thoracal spine
      and posteriorly on the upper cervical region. Fused SPECT/CT images located the
      exact leakage site as at the first costovertebral junction level on the left side
      laterally and on the posterior region of the first and second cervical spine. The
      treatment with epidural blood patch was successful. 

PMID- 25072926
TI  - Value of 18F-FDG PET/CT for early prediction of pathologic response (by residual
      cancer burden criteria) of locally advanced breast cancer to neoadjuvant
      chemotherapy.
AB  - PURPOSE: A relatively new pathologic grading system, called residual cancer
      burden (RCB) criteria (0 to III), for assessing the response to neoadjuvant
      chemotherapy (NCT) of breast cancer has been reported to be more accurate than
      conventional pathologic criteria. This study assesses the value of F-FDG PET/CT
      in early prediction of chemotherapeutic response determined based on these
      criteria. PATIENTS AND METHODS: Thirty-six patients with locally advanced breast
      cancer underwent F-FDG PET/CT before and after the first (just before the second)
      cycle of NCT. Percentage changes (%?) in SUVmax, metabolic tumor volume (MTV),
      and total lesion glycolysis (TLG) between F-FDG PET/CT before and after the first
      cycle of NCT were correlated with RCB index on pathologic specimens after the
      completion of NCT. RESULTS: The %?SUVmax, %?MTV, and %?TLG in the RCB 0/I group
      (n = 5) were all significantly larger than those in the RCB II/III group (n = 31)
      (82.9%, 100%, and 100% vs 45.8%, 83.2%, and 88.0%, respectively, P < 0.01). The
      sensitivity/specificity/accuracy of the optimal cutoff %?SUVmax, %?MTV, and %?TLG
      for discriminating RCB 0/I group from RCB II/III group based on the receiver
      operating characteristic analysis were 80.0%/96.8%/94.4%, 100%/80.6%/83.3%, and
      100%/80.6%/83.3%, respectively. The area under the curve for the 3 parameters was
      0.923, 0.903, and 0.884, respectively, and not statistically different.
      CONCLUSIONS: The %Deltametabolic parameters derived from F-FDG PET/CT studies
      performed before and after the first cycle of NCT in patients with locally
      advanced breast cancer appear to be useful in early prediction of eventual
      therapy response determined based on the RCB pathologic grading system.

PMID- 25072927
TI  - Colon visualization on (99m)Tc-HDP whole-body bone scan due to sigmoid colon
      cancer-related enterovesical fistula.
AB  - An abnormally increased uptake of the bone-seeking agent is rarely observed in
      structures other than the bone and urinary track on bone scintigraphy. The
      general etiologies of soft tissue uptake can be explained by heterotopic
      ossification or dystrophic and metastatic calcification. We report a case of
      serendipitous visualization of the entire colon on bone scintigraphy. Diffuse
      colonic uptake was detected on the whole-body bone scan in a patient with biopsy
      proven sigmoid colon cancer. Additional imaging studies clearly showed direct
      bladder invasion of the sigmoid colon cancer. Imaging findings with a brief
      review of the literature are presented in this article. 

PMID- 25072928
TI  - A frequency and semiquantitative analysis of pathological 68Ga DOTATATE PET/CT
      uptake by primary site-dependent neuroendocrine tumor metastasis.
AB  - The aim of this study was to define the frequency of neuroendocrine neoplasia
      (NEN) metastasis sites based on the primary lesion and create a database of
      SUVmax as a marker of human SSTR (somatostatin receptors) expression by
      semiquantitative analysis in vivo Ga DOTATATE PET/CT. PATIENTS AND METHODS: Two
      hundred forty-five patients, 89 men and 156 women (mean [SD] age, 56.1 [12.8]),
      were imaged 60 to 70 minutes after 120 to 200 MBq (3.2-5.4 mCi) Ga DOTATATE
      injection using a Siemens Medical Solutions Biograph 64 PET/CT TruePoint. Visual
      assessments were made using a multimodality workstation, and sites of increased
      uptake were recorded. Pathological Ga DOTATATE uptake was quantified using
      semiquantitative analysis (SUVmax). RESULTS: In patients with unknown primary
      tumors, Ga DOTATATE PET/CT revealed primary location in 92% (pancreas, 47%;
      intestines, 28%; and lung, 17%).Metastases, with respect to the primary sites,
      were predominantly in the liver (33% vs 49% vs 40%), lymph nodes (24% vs 34% vs
      25%), and bone (10% vs 20% vs 30%). The SUVmax of metastases (mean [SD]) was
      highest in the liver (28.7 [23.5]), followed by the adrenal glands (24.7 [9.7]),
      bone (24.1 [36.8]), lymph nodes (22.5 [24.5]), pancreas (24.9 [28.1]), peritoneum
      (21.9 [24]), and the brain (4.6 [2.9]). CONCLUSIONS: Ga DOTATATE PET/CT is very
      useful in the localization of NEN primary tumors. Ga DOTATATE PET/CT allows for
      visualizations of bone and lymph node metastases, not detected by any other
      modalities, which provides better staging and changes the clinical decision in
      approximately one third of patients.Our study shows that pancreatic NEN presented
      statistically a significantly lower frequency of bone metastases in comparison to
      lung and intestinal NEN. No significant frequency of metastases in the liver and
      lymph nodes based on primary tumors was observed.

PMID- 25072929
TI  - Seeing is believing: hot electron based gold nanoplasmonic optical hydrogen
      sensor.
AB  - We report on the rapid optical detection of gaseous hydrogen using hot electrons
      generated from resonantly excited substrate-based gold nanohemispheres (Au NHs).
      We consider hot electron induced H2 dissociation and the subsequent formation of
      a metastable gold hydride (AuHx) to account for changes in optical transmission.
      The excitation wavelength was varied to demonstrate a maximum response at the
      localized surface plasmon resonance (LSPR) wavelength of the AuNHs. Numerical
      simulations, using the discrete dipole approximation, were employed to
      corroborate the optical changes associated with the formation of metastable AuHx.
      Finite time difference domain (FDTD) calculations were also performed to account
      for the enhanced photocatalytic activity arising due to the confinement of
      electric fields by the Au NHs. FDTD simulations show that the excitation of the
      Au NHs plasmon modes generates stronger electric fields at the interface in
      comparison to a spherical geometry of similar dimensions.

PMID- 25072930
TI  - Genetic organization of interphase chromosome bands and interbands in Drosophila
      melanogaster.
AB  - Drosophila melanogaster polytene chromosomes display specific banding pattern;
      the underlying genetic organization of this pattern has remained elusive for many
      years. In the present paper, we analyze 32 cytology-mapped polytene chromosome
      interbands. We estimated molecular locations of these interbands, described their
      molecular and genetic organization and demonstrate that polytene chromosome
      interbands contain the 5' ends of housekeeping genes. As a rule, interbands
      display preferential "head-to-head" orientation of genes. They are enriched for
      "broad" class promoters characteristic of housekeeping genes and associate with
      open chromatin proteins and Origin Recognition Complex (ORC) components. In two
      regions, 10A and 100B, coding sequences of genes whose 5'-ends reside in
      interbands map to constantly loosely compacted, early-replicating, so-called
      "grey" bands. Comparison of expression patterns of genes mapping to late
      replicating dense bands vs genes whose promoter regions map to interbands shows
      that the former are generally tissue-specific, whereas the latter are represented
      by ubiquitously active genes. Analysis of RNA-seq data (modENCODE-FlyBase)
      indicates that transcripts from interband-mapping genes are present in most
      tissues and cell lines studied, across most developmental stages and upon various
      treatment conditions. We developed a special algorithm to computationally process
      protein localization data generated by the modENCODE project and show that
      Drosophila genome has about 5700 sites that demonstrate all the features shared
      by the interbands cytologically mapped to date. 

PMID- 25072932
TI  - CDKN2A(p16) and HRAS are frequently mutated in vulvar squamous cell carcinoma.
AB  - BACKGROUND: Two etiologic pathways of vulvar cancer are known, a human
      papillomavirus (HPV)- and a TP53-associated route, respectively, but other
      genetic changes may also play a role. Studies on somatic mutations in vulvar
      cancer other than TP53 are limited in number and size. In this study, we
      investigated the prevalence of genetic mutations in 107 vulvar squamous cell
      carcinomas (VSCCs). METHODS: A total of 107 paraffin-embedded tissue samples of
      primarily surgically treated VSCCs were tested for HPV infection and screened for
      mutations in 14 genes (BRAF, CDKN2A(p16), CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2,
      HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53) using Sanger sequencing and
      mass spectrometry. RESULTS: Mutations were detected in 7 genes. Of 107 VSCCs, 66
      tumors (62%) contained at least one mutation (TP53=58, CDKN2A(p16)=14, HRAS=10,
      PIK3CA=7, PPP2R1A=3, KRAS=1, PTEN=1). Mutations occurred most frequently in HPV
      negative samples. Five-year survival was significantly worse for patients with a
      mutation (47% vs 59%, P=.035), with a large effect from patients carrying HRAS
      mutations. CONCLUSION: Somatic mutations were detected in 62% of VSCCs. As
      expected, HPV infection and TP53-mutations play a key role in the development of
      VSCC, but CDKN2A(p16), HRAS, and PIK3CA-mutations were also frequently seen in
      HPV-negative patients. Patients with somatic mutations, especially HRAS
      mutations, have a significantly worse prognosis than patients lacking these
      changes, which could be of importance for the development of targeted therapy.

PMID- 25072931
TI  - Is diabetes mellitus associated with increased incidence and disease-specific
      mortality in endometrial cancer? A systematic review and meta-analysis of cohort
      studies.
AB  - OBJECTIVE: To assess the association between diabetes mellitus (DM) and the
      incidence and disease-specific mortality of endometrial cancer (EC). METHODS:
      MEDLINE, EMBASE and conference abstracts of the 2011-2013 Annual Meetings of
      Society of Gynecological Oncology were searched for reports of original cohort
      studies that enrolled diabetic and non-diabetic women who were free of EC at
      baseline to compare the incidence and disease-specific mortality of EC by DM
      status. The included reports were examined for demographic characteristics of
      study populations, study design, effect measures and risk of bias. Statistical
      heterogeneity was evaluated with Chi-square test of the Cochrane Q statistics at
      the 0.05 significance level and I(2) statistic. Publication bias was assessed by
      visual examination of a funnel plot and the Egger's test for small-study effects.
      RESULTS: Twenty-nine cohort studies (17 prospective, 12 retrospective) were
      eligible for this review, 23 of which reported EC incidence, five reported
      disease-specific mortality and one reported both. For incidence of EC among women
      with versus without DM, the summary relative risk (RR) was 1.89 (95%CI, 1.46
      2.45; p<0.001) and the summary incidence rate ratio was 1.61 (95%CI, 1.51-1.71;
      p<0.001). The pooled RR of disease-specific mortality was 1.32 (95%CI, 1.10-1.60;
      p=0.003), while results in the studies reporting standardized mortality ratios
      were inconsistent. There remains considerable amount of clinical and
      methodological heterogeneity among the included studies; moreover, the hazard
      ratios for incident EC showed significant statistical heterogeneity and therefore
      were not quantitatively synthesized. CONCLUSIONS: There is consistent evidence
      for an independent association between DM and an increased risk of incident EC,
      while the association between DM and EC-specific mortality remains uncertain.
      Further studies with better considerations for selection bias, information bias
      and confounding will further facilitate causal inference involving DM and EC.

PMID- 25072933
TI  - Optimized spatial priorities for biodiversity conservation in China: a systematic
      conservation planning perspective.
AB  - By addressing several key features overlooked in previous studies, i.e. human
      disturbance, integration of ecosystem- and species-level conservation features,
      and principles of complementarity and representativeness, we present the first
      national-scale systematic conservation planning for China to determine the
      optimized spatial priorities for biodiversity conservation. We compiled a spatial
      database on the distributions of ecosystem- and species-level conservation
      features, and modeled a human disturbance index (HDI) by aggregating information
      using several socioeconomic proxies. We ran Marxan with two scenarios (HDI
      ignored and HDI-considered) to investigate the effects of human disturbance, and
      explored the geographic patterns of the optimized spatial conservation
      priorities. Compared to when HDI was ignored, the HDI-considered scenario
      resulted in (1) a marked reduction (~9%) in the total HDI score and a slight
      increase (~7%) in the total area of the portfolio of priority units, (2) a
      significant increase (~43%) in the total irreplaceable area and (3) more
      irreplaceable units being identified in almost all environmental zones and highly
      disturbed provinces. Thus the inclusion of human disturbance is essential for
      cost-effective priority-setting. Attention should be targeted to the areas that
      are characterized as moderately-disturbed, <2,000 m in altitude, and/or
      intermediately- to extremely-rugged in terrain to identify potentially important
      regions for implementing cost-effective conservation. We delineated 23 primary
      large-scale priority areas that are significant for conserving China's
      biodiversity, but those isolated priority units in disturbed regions are in more
      urgent need of conservation actions so as to prevent immediate and severe
      biodiversity loss. This study presents a spatially optimized national-scale
      portfolio of conservation priorities--effectively representing the overall
      biodiversity of China while minimizing conflicts with economic development. Our
      results offer critical insights for current conservation and strategic land-use
      planning in China. The approach is transferable and easy to implement by end
      users, and applicable for national- and local-scale systematic conservation
      prioritization practices.

PMID- 25072934
TI  - Thermodynamics of copolymer solutions: how the pair interactions contribute to
      the overall effect.
AB  - Vapor pressure measurements were performed for solutions of poly(methyl
      methacrylate-ran-tert-butyl methacrylate) with different weight fractions of tert
      butyl methacrylate units, and their parental homopolymers in chloroform at 323 K,
      over a large domain of concentrations. The Flory-Huggins interaction parameters
      obtained from these experimental investigations show complex dependences of the
      Flory-Huggins interaction parameter on concentration and copolymer composition.
      This behavior can be modeled by taking into account an approach which considers
      the ability of the polymers to rearrange in a response to changes in their
      molecular surroundings [Adv. Polym. Sci. 2011, 238, 1-66]. According to this
      concept, the mixing process is subdivided into two clearly separable steps and
      accounts for the specific interactions between the solvent and copolymer
      segments. 

PMID- 25072935
TI  - Multicopper models for the laccase active site: effect of nuclearity on
      electrocatalytic oxygen reduction.
AB  - Cu complexes of 2,2'-dipicolylamine (DPA) were prepared and tested as
      electrocatalysts for the oxygen reduction reaction (ORR). To study the effect of
      multinuclearity on the ORR, two Cu-DPA units were connected with a flexible
      linker, and a third metal-binding pocket was installed in the ligand framework.
      ORR onset potentials and the diffusion-limited current densities of di- and
      tricopper complexes of DPA derivatives were found to be comparable to those of
      the simpler Cu-DPA system. Electrochemical analyses, crystallographic data, and
      metal-substitution studies suggested that Cu complexes of DPA derivatives reacted
      with O2 via a binuclear intermolecular pathway but that the Cu center in the
      third binding site did not participate in the ORR process. This study highlights
      the viability of Cu-DPA complexes to mimic the T3-site of laccase, and serves as
      a guide for designing future laccase models. 

PMID- 25072936
TI  - Age-related mercury contamination and relationship with luteinizing hormone in a
      long-lived Antarctic bird.
AB  - Seabirds, as long-lived top predators, accumulate contaminants such as mercury
      (Hg), an established endocrine disruptor. In long lived species hormonal
      secretion varies with age; therefore, Hg-induced endocrine disruption may be
      exacerbated in some age classes. Here we investigated relationships between blood
      total Hg and luteinizing hormone (LH, a key pituitary hormone for the onset of
      breeding), in pre-laying known-age (11-45 years old) snow petrels (Pagodroma
      nivea) from Adelie Land, Antarctica. We predicted that 1) blood Hg would increase
      with advancing age as a consequence of bio-accumulation; and that 2) increasing
      blood Hg would be related to decreased concentrations of LH in the most Hg
      contaminated individuals. Hg concentrations were higher in females than in males
      (p<0.001), and contrary to our prediction, decreased with advancing age in males
      (p = 0.009) and tended to do so in females (p = 0.06). The analysis of stable
      isotopes (delta13C and delta15N) suggested that this unexpected pattern could
      originate from age and sex-related variations in trophic niche, and hence Hg
      exposure. Regarding LH, our prediction was only supported in young birds (<=23
      years) where baseline LH was inversely correlated with Hg concentrations (p =
      0.04). Hg burden did not predict baseline LH or GnRH-induced LH in birds that
      were more than 23 years old. These results show that age and contaminants may
      interfere with major endocrine mechanisms and, together with other recent
      studies, support the view that Hg could be connected to LH secretion and could
      then impair the fitness of long-lived birds. 

PMID- 25072937
TI  - Effect of arginase inhibition on ischemia-reperfusion injury in patients with
      coronary artery disease with and without diabetes mellitus.
AB  - BACKGROUND: Arginase competes with nitric oxide synthase for their common
      substrate L-arginine. Up-regulation of arginase in coronary artery disease (CAD)
      and diabetes mellitus may reduce nitric oxide bioavailability contributing to
      endothelial dysfunction and ischemia-reperfusion injury. Arginase inhibition
      reduces infarct size in animal models. Therefore the aim of the current study was
      to investigate if arginase inhibition protects from endothelial dysfunction
      induced by ischemia-reperfusion in patients with CAD with or without type 2
      diabetes ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02009527). METHODS: Male
      patients with CAD (n = 12) or CAD + type 2 diabetes (n = 12), were included in
      this cross-over study with blinded evaluation. Endothelium-dependent
      vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial
      artery before and after 20 min ischemia-reperfusion during intra-arterial
      infusion of the arginase inhibitor (Nomega-hydroxy-nor-L-arginine, 0.1 mg/min) or
      saline. RESULTS: The forearm ischemia-reperfusion was well tolerated. Endothelium
      independent vasodilatation was assessed by sublingual nitroglycerin. Ischemia
      reperfusion decreased FMD in patients with CAD from 12.7+/-5.2% to 7.9+/-4.0%
      during saline administration (P<0.05). Nomega-hydroxy-nor-L-arginine
      administration prevented the decrease in FMD in the CAD group (10.3+/-4.3% at
      baseline vs. 11.5+/-3.6% at reperfusion). Ischemia-reperfusion did not
      significantly reduce FMD in patients with CAD + type 2 diabetes. However, FMD at
      reperfusion was higher following nor-NOHA than following saline administration in
      both groups (P<0.01). Endothelium-independent vasodilatation did not differ
      between the occasions. CONCLUSIONS: Inhibition of arginase protects against
      endothelial dysfunction caused by ischemia-reperfusion in patients with CAD.
      Arginase inhibition may thereby be a promising therapeutic strategy in the
      treatment of ischemia-reperfusion injury.

PMID- 25072938
TI  - Salvage radiotherapy after radical prostatectomy: prediction of biochemical
      outcomes.
AB  - INTRODUCTION: A significant proportion of patients undergoing salvage
      radiotherapy (RT) for biochemical recurrence (BCR) following radical
      prostatectomy (RP) may again experience BCR after salvage RT. Thus, we evaluated
      the clinical significances of different parameters on the biochemical outcome of
      RT in salvage setting. METHODS: We reviewed the records of 212 patients who
      underwent salvage RT between November 2003 and December 2012 for BCR following
      primary RP. BCR-free survivals after salvage RT were estimated using the Kaplan
      Meier method. Cox proportional hazard regression models were used to evaluate the
      impacts of clinicopathologic parameters on BCR following salvage RT. RESULTS: The
      overall median follow-up duration was 63.5 months. The BCR-free survival rate
      after salvage RT was 58.2% at 5 years. Multivariate analysis showed that a pre-RT
      prostate-specific antigen (PSA) level of <=0.5 ng/mL, a pre-RT PSA doubling time
      (PSADT) of >4.5 months, concomitant androgen deprivation therapy (ADT) with
      salvage RT, and a positive surgical margin were independent predictors of
      favorable biochemical outcomes after salvage RT (hazard ratios [HR] = 3.012,
      1.132, 2.000, and 1.805, respectively, p = less than 0.001, 0.013, 0.005, and
      0.036, respectively). In the early (pre-RT PSA <=0.5 ng/mL) salvage RT setting,
      concomitant ADT administration was also shown to be significantly associated with
      higher risk of BCR-free survival following salvage RT (HR = 2.611, p = 0.038).
      CONCLUSION: Lower pre-RT PSA value, longer PSADT before salvage RT, concomitant
      ADT administration, and a positive surgical margin were significant predictors of
      favorable biochemical outcomes following salvage RT performed for BCR after
      primary RP.

PMID- 25072939
TI  - Enhanced biosensing resolution with foundry fabricated individually addressable
      dual-gated ISFETs.
AB  - The adaptation of semiconductor technologies for biological applications may lead
      to a new era of inexpensive, sensitive, and portable diagnostics. At the core of
      these developing technologies is the ion-sensitive field-effect transistor
      (ISFET), a biochemical to electrical transducer with seamless integration to
      electronic systems. We present a novel structure for a true dual-gated ISFET that
      is fabricated with a silicon-on-insulator (SOI) complementary metal-oxide
      semiconductor process by Taiwan Semiconductor Manufacturing Company (TSMC). In
      contrast to conventional SOI ISFETs, each transistor has an individually
      addressable back-gate and a gate oxide that is directly exposed to the solution.
      The elimination of the commonly used floating gate architecture reduces the
      chance of electrostatic discharge and increases the potential achievable
      transistor density. We show that when operated in a "dual-gate" mode, the
      transistor response can exhibit sensitivities to pH changes beyond the Nernst
      limit. This enhancement in sensitivity was shown to increase the sensor's signal
      to-noise ratio, allowing the device to resolve smaller pH changes. An improved
      resolution can be used to enhance small signals and increase the sensor accuracy
      when monitoring small pH dynamics in biological reactions. As a proof of concept,
      we demonstrate that the amplified sensitivity and improved resolution result in a
      shorter detection time and a larger output signal of a loop-mediated isothermal
      DNA amplification reaction (LAMP) targeting a pathogenic bacteria gene, showing
      benefits of the new structure for biosensing applications. 

PMID- 25072940
TI  - Catalytic asymmetric synthesis of 4-nitropyrazolidines: an access to optically
      active 1,2,3-triamines.
AB  - The first catalytic enantio- and diastereoselective synthesis of 4
      nitropyrazolidines is presented. Asymmetric hydrogen-bonding activation of nitro
      olefins facilitated the 1,3-dipolar cycloaddition with hydrazones, affording
      optically active 4-nitropyrazolidines containing three continuous stereogenic
      centers as a single diastereomer in up to 99% ee. Furthermore, it is demonstrated
      that the optically active 4-nitropyrazolidines can be applied as precursors for
      the synthesis of highly interesting 1,2,3-triamines. 

PMID- 25072941
TI  - The Associations Between Executive Functions' Capacities, Performance Process
      Skills, and Dimensions of Participation in Activities of Daily Life Among
      Children of Elementary School Age.
AB  - Effective executive functions (EFs) are crucial for efficient daily functioning.
      Daily functioning or involvement in life situations is defined as "participation"
      (International Classification of Functioning, Disability, and Health [ICF]; World
      Health Organization, 2001). Yet associations between them have been inadequately
      studied for children. The present study aimed to explore the associations between
      EFs and child participation. Participants were 60 typically developing children
      aged 6 to 9 years old and their parents. The children were individually evaluated
      using five EF cognitive tests. The parents completed three questionnaires: the
      Children Participation Questionnaire, the Process Skills (the observed executive
      performance) Questionnaire, and the Environmental Restrictions Questionnaire.
      Most of the EF scores were associated with the child's age. A unique contribution
      of executive capacities was found for the "independence" aspect of child
      participation, though the quantum of contribution was limited compared with the
      other predictors' process skills and environmental restrictions. In the context
      of child participation, EFs should be studied through multivariate analysis, as
      otherwise, the unique contribution of executive capacities measured by
      neuropsychological cognitive tests are likely to be ignored. Process skills are
      crucial for a child's independence and autonomy in daily functioning. These
      findings are supported by the capacity-performance distinction suggested by the
      ICF model.

PMID- 25072942
TI  - Sustained impact of short-term international medical mission trips: resident
      perspectives.
AB  - PURPOSE: To assess perspectives of residents: (1) who participated in short-term
      international medical mission trips (STIMMTs) as medical students regarding
      impact of the experiences on their professional development; and (2) who did not
      participate in STIMMTs regarding barriers to participation. METHODS: Three
      hundred seventy-nine residents from 16 programs at two Florida institutions
      completed surveys requesting Participant and Trip Details and Impact of
      Participation (including items rating learning, cultural competency, and social
      responsibility). RESULTS: One hundred thirty-one residents participated in at
      least one STIMMT. They identified improved adaptability to new healthcare
      settings, communication with patients and professionals from different
      backgrounds, and appreciation for the impact of culture on health as positive
      outcomes. Leading barriers to STIMMT participation included cost, timing, and
      lack of availability. CONCLUSIONS: Years after participation in STIMMTs,
      residents perceived sustained benefits in cultural competency, communication
      skills, adaptability, and desire for service. Institutions may consider
      facilitating STIMMTs as one way to address standards specified by accrediting
      authorities to provide training in cultural competency, social responsibility,
      altruism, and understanding the importance of caring for underserved populations.
      Barriers to STIMMT participation may be reduced through availability of
      institution-sponsored scholarships, identification of external grant and
      scholarship opportunities, and coordination of fund-raising activities.

PMID- 25072943
TI  - Reuleaux triangle disks: new shape on the block.
AB  - We report here the unprecedented preparation of Reuleaux triangle disks. The
      hydrolysis and precipitation of bismuth nitrate in an ethanol-water system with
      2,3-bis(2-pyridyl)pyrazine yielded basic bismuth nitrate Reuleaux triangle disks.
      Analysis of the intermediates provided insights into the mystery behind the
      formation of the Reuleaux triangle disk, revealing a unique growth process. The
      report of a facile method to prepare crystals of a novel shape in high yield,
      with good homogeneity, and with excellent reproducibility is expected to unlock
      new research directions in multiple disciplines. 

PMID- 25072944
TI  - Palladium-catalyzed carbonylative addition of aryl bromides to arylalkynes: a
      simple and efficient method for chalcone synthesis.
AB  - Palladium-catalyzed carbonylative addition of aryl bromides to terminal
      arylalkynes was carried out to produce chalcones in satisfactory to excellent
      yields. The unprecedented carbonylation reaction proceeded smoothly under mild
      conditions in the presence of a simple palladium catalyst system
      (PdCl2/DPPB/(i)Pr2NEt) in N,N-dimethyl formamide. 

PMID- 25072945
TI  - Measuring unbound versus total vancomycin concentrations in serum and plasma:
      methodological issues and relevance.
AB  - BACKGROUND: Studies on the unbound fraction (fu) of vancomycin report highly
      variable results. Great controversy also exists about the correlation between
      unbound and total vancomycin concentrations. As differences in (pre-)analytic
      techniques may explain these findings, we investigated the impact of the
      procedure used to isolate unbound vancomycin in serum/plasma on fu and the
      correlation between total and unbound concentrations. METHODS: Patient samples (n
      = 39) were analyzed for total and unbound vancomycin concentrations after
      ultrafiltration (UF, Centrifree at 4 degrees C and 37 degrees C) or equilibrium
      dialysis (ED, using a Fast Micro-Equilibrium Dialyzer at 37 degrees C) on an
      Architect i2000SR. To investigate correlations with potential binding proteins,
      total protein, albumin, alpha-1-acid glycoprotein, and IgA concentrations were
      also measured. RESULTS: The median fu after ED was 72.5% [interquartile range
      (IQR), 68.7%-75.0%]. Ultrafiltration at 4 degrees C and 37 degrees C resulted in
      a median fu of 51.6% (IQR, 48.6%-54.8%) and 75.2% (IQR, 69.3%-78.6%),
      respectively, with no significant difference between unbound vancomycin
      concentrations after ED and UF at 37 degrees C (P = 0.13). Unbound concentrations
      obtained through ED and UF correlated linearly (4 degrees C: r = 0.9457; 37
      degrees C: r = 0.9478; both P < 0.0001). Linear mixed-model regression showed
      that total vancomycin as such was the predominant determinant for the unbound
      concentration, allowing a reliable prediction (mean bias +/- SD, 5.0% +/- 7.6%).
      The studied protein concentrations were of no added value in predicting the
      unbound concentration. CONCLUSIONS: Vancomycin fu after UF at 4 degrees C was on
      average 30.6% lower than that after UF at 37 degrees C, demonstrating the
      importance of temperature during UF. Ultrafiltration at 37 degrees C resulted in
      unbound vancomycin concentrations equivalent with ED. As the unbound
      concentration could be reliably predicted based on total vancomycin
      concentrations as such, measurement of unbound vancomycin concentrations has
      little added value over measurements of total vancomycin concentrations.

PMID- 25072946
TI  - Development and validation of an HPLC-UV method for pazopanib quantification in
      human plasma and application to patients with cancer in routine clinical
      practice.
AB  - BACKGROUND: Pazopanib, a new oral angiogenesis inhibitor, has demonstrated
      clinical activity against multiple solid tumors and was approved for the
      treatment of patients with advanced renal cell carcinoma. As an exposure-response
      relationship has been observed for pazopanib, its therapeutic drug monitoring
      could be a valuable tool in clinical practice. Therefore, the aim of this study
      was to develop and validate a selective and precise high performance liquid
      chromatography-ultraviolet method for the measurement of pazopanib in plasma from
      patients with cancer. METHODS: After liquid-liquid extraction with diethyl ether,
      pazopanib and gefitinib (internal standard) were separated using isocratic
      elution on an Ultrabase C18 column using a mobile phase consisting of a mixture
      in vol/vol proportion of 47:53 of ammonium acetate (pH, 7; 0.02 mol/L) and
      acetonitrile/methanol (70:30, vol/vol) pumped at a constant flow rate of 1
      mL/min. Quantification was performed at 260 nm. Method validation was undertaken
      as per the guidelines for Bioanalytical Method Validation published by the Food
      and Drug Administration and European Medicines Agency. RESULTS: Calibration
      curves were linear over the range 0.5-100 mcg/mL. Interday and intraday
      coefficients of variations were less than 4.5%. The limit of detection and the
      lower limit of quantification were 0.2 and 0.5 mcg/mL, respectively. Recovery of
      pazopanib from plasma was >80%. CONCLUSIONS: This is the first high performance
      liquid chromatography-ultraviolet method for pazopanib quantification that has
      been validated within a wide range of plasma concentrations and is a suitable
      method for therapeutic drug monitoring of pazopanib.

PMID- 25072947
TI  - Multicenter evaluation of the thermo scientific prelude for measurement of
      immunosuppressant drugs using sample preparation liquid chromatography-tandem
      mass spectrometry.
AB  - Immunosuppressant drugs (ISDs) are commonly prescribed to solid organ transplant
      patients. Their narrow therapeutic index and potential for toxicity necessitates
      careful monitoring of blood concentrations. Liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) methods are increasingly used for ISD measurement.
      However, there remain many challenges with this methodology, particularly
      regarding interassay variability. The Thermo Scientific Prelude is an online
      extraction/liquid chromatography platform that uses turbulent flow technology
      coupled with MS/MS. A multicenter evaluation of the Prelude for the measurement
      of cyclosporine A, tacrolimus, and sirolimus is described. ISDs were measured at
      each site using standardized protocols. Sample preparation liquid chromatography
      MS/MS was performed using the Prelude coupled to a TSQ Vantage. Chromatography
      was achieved with a Cyclone-P TurboFlow/Accucore C8 column combination using a
      multisolvent loading and eluting pump system. Mass spectrometry acquisitions were
      performed in selective reaction monitoring mode and data processed using
      TraceFinder (version 3.1). Multisite mean imprecision for cyclosporine A ranged
      from 8.8% (54 mcg/L) to 9.8% (450 mcg/L); for tacrolimus, 4.7% (15.5 mcg/L) to
      12.6% (2.5 mcg/L); for sirolimus, 7.4% (19.9 mcg/L) to 16.5% (2.6 mcg/L).
      Approximately 110 specimens were used for method comparison. For cyclosporine A,
      mean bias against the multisite mean ranged from -18% to 1%; for tacrolimus,
      values ranged from -7% to 4%; for sirolimus, values ranged from -4% to 2%.
      Comparisons of multisite mean Prelude results with routine ISD method results was
      also performed for cyclosporine A (slope = 0.7878, intercept = 24.16, r = 0.98),
      tacrolimus (slope = 0.9391, intercept = 0.1017, r = 98), and sirolimus (slope =
      0.9618, intercept = 0.1483, r = 0.97). The Prelude ISD method offers acceptable
      and comparable multisite performance. This study has also highlighted the
      importance of adopting standardized protocols and LC-MS/MS methods for better
      comparability between ISD assays. 

PMID- 25072948
TI  - Clinical consequences of a miscalibrated digoxin immunoassay.
AB  - BACKGROUND: A routine audit revealed that the analytical method used to measure
      digoxin concentrations by our statewide pathology provider in 2009 was
      underestimating digoxin concentrations by 10%. The assay was recalibrated by the
      manufacturer in 2010, but clinical outcomes of the underestimation were never
      measured. This is a pilot study to describe the prescribing behavior around out
      of-range digoxin concentrations and to assess whether miscalibrated digoxin
      immunoassays contribute to clinically relevant effects, as measured by
      inappropriate alterations in digoxin doses. METHODS: About 30,000 digoxin
      concentrations across the State Hospital system were obtained in 2 periods before
      and after recalibration of the digoxin assay. Digoxin concentration means were
      calculated and compared and were statistically significantly different.
      Subsequently, a single-centered retrospective review of 50 randomly chosen charts
      was undertaken to study the clinical implications of the underestimated
      concentrations. RESULTS: Mean digoxin concentrations for 2009 and 2011 were
      significantly different by 8.8% (confidence interval, 7.0%-10.6%). After
      recalculating the 2009 concentrations to their "corrected" values, there was a
      16% increase in the number of concentrations within the range when compared with
      the 2011 concentrations (41.48% versus 48.04%). However, overall, this did not
      cause unnecessary dose changes in patients who were "borderline" or outside the
      therapeutic range when compared with controls (P = 0.10). The majority of
      decisions were based on the clinical impression rather than concentration alone
      (85.1% versus 14.9%), even when the concentration was outside the "therapeutic
      range." CONCLUSIONS: Although recalculating digoxin concentrations measured
      during 2009 to their corrected values produced a significant change in
      concentration and values inside and outside the range, this does not seem to have
      had an influence on patient treatment. Rather, clinicians tended to use the
      clinical impression to dose digoxin.

PMID- 25072949
TI  - Intestinal cryptosporidiosis in a 6-year-old child with alpha1-antitrypsin
      deficiency.

PMID- 25072950
TI  - A greenhouse-scale photosynthetic microbial bioreactor for carbon sequestration
      in magnesium carbonate minerals.
AB  - A cyanobacteria dominated consortium collected from an alkaline wetland located
      near Atlin, British Columbia, Canada accelerated the precipitation of platy
      hydromagnesite [Mg5(CO3)4(OH)2.4H2O] in a linear flow-through experimental model
      wetland. The concentration of magnesium decreased rapidly within 2 m of the
      inflow point of the 10-m-long (~1.5 m(2)) bioreactor. The change in water
      chemistry was monitored over two months along the length of the channel.
      Carbonate mineralization was associated with extra-cellular polymeric substances
      in the nutrient-rich upstream portion of the bioreactor, while the lower part of
      the system, which lacked essential nutrients, did not exhibit any hydromagnesite
      precipitation. A mass balance calculation using the water chemistry data produced
      a carbon sequestration rate of 33.34 t of C/ha per year. Amendment of the
      nutrient deficiency would intuitively allow for increased carbonation activity.
      Optimization of this process will have application as a sustainable mining
      practice by mediating magnesium carbonate precipitation in ultramafic mine
      tailings storage facilities. 

PMID- 25072951
TI  - Mammalian serum albumins as a chiral mediator library for bio-supramolecular
      photochirogenesis: optimizing enantiodifferentiating photocyclodimerization of 2
      anthracenecarboxylate.
AB  - A simple strategy for choosing optimal bio-supramolecular mediators from the
      mammalian serum albumin library is proposed for bimolecular photochirogenic
      reactions. Thus, the enantiodifferentiating photocyclodimerization of 2
      anthracencecarboxylate (AC) was optimized in chemical and optical yields, when
      mediated by porcine and canine serum albumins, both of which bound two AC
      molecules in the first productive site to give the (P)-enantiomer of syn-head-to
      tail-cyclodimer in 69% yield and 89% enantiomeric excess (ee) for the former but
      the (M)-enantiomer in 77% yield and 97% ee for the latter. 

PMID- 25072952
TI  - Beneficial effects of soy supplementation on postmenopausal atherosclerosis are
      dependent on pretreatment stage of plaque progression.
AB  - OBJECTIVE: The objective of this study was to use a well-established monkey model
      of atherosclerosis to determine how life stage and preexisting atherosclerosis
      influence the effectiveness of high-isoflavone soy diet in inhibiting progression
      of atherosclerosis. METHODS: For 34 months, premenopausal monkeys were fed an
      atherogenic diet, with protein derived primarily from either animal sources
      (casein-lactalbumin [CL], n = 37) or high-isoflavone soy beans (Soy, n = 34).
      Animals were ovariectomized and randomized to groups fed the same diet (CL-CL, n
      = 20; Soy-Soy, n = 17) or an alternate diet (CL-Soy, n = 17; Soy-CL, n = 17) for
      an additional 34 months. At ovariectomy, the left common iliac artery was removed
      to determine the amount of premenopausal atherosclerosis. At necropsy, the right
      common iliac artery and coronary arteries were collected, and atherosclerosis
      extent was quantified. CL-CL condition was considered "control." RESULTS:
      Modeling Asian women who remain in Asia, monkeys fed soy protein both
      premenopausally and postmenopausally had a markedly reduced extent of coronary
      artery atherosclerosis relative to CL controls (P = 0.008). The subset of animals
      that modeled Asian women who migrate to a Western country (consuming soy
      premenopausally and CL postmenopausally) had increased progression of
      postmenopausal iliac artery atherosclerosis (P = 0.003) and was not protected
      against the development of coronary artery atherosclerosis relative to controls.
      Relevant to the administration of soy diets to postmenopausal Western women,
      monkeys fed CL premenopausally and switched to soy postmenopausally derived
      atheroprotective benefits only if they began the postmenopausal treatment period
      with relatively small (below the median) plaques. Relative to controls, this
      group (with small plaques at ovariectomy) had reduced progression of iliac
      atherosclerosis (P = 0.038) and smaller coronary artery plaques (P = 0.0001) that
      were less complicated (P = 0.05) relative to controls. CONCLUSIONS: The results
      suggest that significant atheroprotective benefits of dietary soy are derived
      from treatment that begins premenopausally and continues postmenopausally or from
      treatment that is started during early postmenopause (when plaques are still
      small).

PMID- 25072953
TI  - Variations in glomerular filtration rate are associated with subclinical
      atherosclerosis in healthy postmenopausal women.
AB  - OBJECTIVE: This study aims to evaluate the potential effects of renal function
      variations on vascular structure before the development of hypertension. METHODS:
      This pilot study included 141 postmenopausal women without evidence of renal
      dysfunction or hypertension. Markers of renal function and levels of glomerular
      filtration rate (GFR)--using standard calculations (GFR based on levels of
      creatinine [GFR(epi)]) and newer creatinine and/or cystatin calculations (GFR
      based on levels of creatinine and cystatin [GFR(cr cystatin)] and GFR based on
      levels of cystatin [GFR(cystatin)])--were associated with hemodynamic parameters
      and markers of vascular structure (intima-media thickness [IMT] and presence of
      atheromatous plaques in carotid and femoral arteries). RESULTS: Levels of
      GFR(epi), GFR(cr cystatin), and GFR(cystatin) exhibited a significant negative
      correlation with femoral artery IMT, whereas levels of GFR(epi) correlated
      significantly with mean carotid bulb (CB) IMT. Multivariate analysis showed that
      CB-IMT was predicted by GFR(epi) levels and age (beta-coefficient = -0.212, P =
      0.020), whereas femoral artery IMT was predicted by GFR(epi) levels (beta
      coefficient = -0.293, P = 0.001). GFR(epi) levels lower than the 25th percentile
      were associated with higher CB-IMT (P = 0.009), femoral artery IMT (P = 0.001),
      and combined IMT (P = 0.035) compared with higher GFR(epi) levels. Moreover,
      GFR(epi) levels greater than the 25th percentile were associated with lower odds
      for the presence of atherosclerotic plaques at the CB and carotid arteries
      combined (CB: odds ratio, 0.146; P = 0.006; combined: odds ratio, 0.249; P =
      0.043) compared with lower GFR(epi) levels. CONCLUSIONS: A mild decrease in renal
      function within normal limits of GFR is independently associated with the
      presence of subclinical atherosclerosis in a sample of apparently healthy young
      postmenopausal women. Assessment of GFR using creatinine (vs cystatin C) levels
      is a more sensitive marker of its association with IMT and atherosclerotic
      plaques in this postmenopausal population.

PMID- 25072954
TI  - Relationship between cystatin C and metabolic syndrome among Chinese
      premenopausal and postmenopausal women without recognized chronic kidney disease.
AB  - OBJECTIVE: Although studies have shown that elevated cystatin C (Cys-C) levels
      are associated with the risk of metabolic syndrome (MetS) in the general
      population, few studies have examined the relationship between serum Cys-C levels
      and MetS, stratified by menopause status, among women in China. Therefore, we
      conducted this study to assess the relationship between Cys-C levels and MetS in
      Chinese premenopausal and postmenopausal women. METHODS: We performed a cross
      sectional analysis of the baseline data of 1,428 Chinese community-dwelling women
      who participated in the annual health checkup. MetS was defined by the updated
      National Cholesterol Education Program/Adult Treatment Panel III criteria. Binary
      logistic regression analysis was performed to estimate the association between
      Cys-C levels and MetS. One-way analysis of variance, followed by posttest for
      linear trends, was performed to evaluate the relationships between Cys-C levels
      and the number of MetS components. Ordinal regression analysis was used to
      determine whether menopause status and MetS components contribute to elevated
      levels of Cys-C. RESULTS: The mean level of Cys-C was significantly higher in
      women with MetS than in those without MetS among both premenopausal and
      postmenopausal women, showing a progressive increase (P for trend < 0.001) in
      parallel with the progressive increment in the number of MetS components in all
      women. Higher Cys-C levels were found to be associated with the presence of MetS
      after adjusting for age, body mass index, and estimated glomerular filtration
      rate in all women. The higher odds ratio changed little, even after further
      adjustment for serum blood nitrogen, total cholesterol, low-density lipoprotein
      cholesterol, drinking status, and smoking status. Elevated Cys-C level was
      significantly associated with postmenopause status (P = 0.007), increased waist
      circumference (P = 0.006), and elevated blood pressure (P = 0.025). CONCLUSIONS:
      Higher serum Cys-C levels are positively and independently associated with the
      presence of MetS in Chinese premenopausal and postmenopausal women. Elevated Cys
      C levels are significantly associated with postmenopause status.

PMID- 25072955
TI  - Another option for menopausal vasomotor symptoms without negative impact on
      weight and sexual function.

PMID- 25072956
TI  - Mammographic breast density: from Wolfe and beyond.

PMID- 25072957
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health.

PMID- 25072959
TI  - The arachidonic acid-LTB4-BLT2 pathway enhances human B-CLL aggressiveness.
AB  - Deregulation of the oxidative cascade of poly-unsaturated fatty acids (PUFAs) has
      been associated with several cancers, including chronic lymphocytic leukemia (B
      CLL). Leukotriene B4 (LTB4), a metabolite of arachidonic acid (AA), is produced
      by B-CLL and contributes to their survival. The aim of the present study was to
      analyze the activity of the oxidative cascade of PUFAs in B-CLL. Purified B cells
      from patients and normal B CD5 positive cells were subjected to flow cytometry,
      Western-blot and RT-qPCR analyses. LTB4 plasma and intracellular concentrations
      were determined by ELISA. Our results showed that aggressive B-CLL tumor cells,
      i.e. cells with an annual proliferation index above 2, over-expressed calcium
      dependent and calcium-independent phospholipases A2 (cPLA2-alpha and iPLA2-beta,
      respectively), 5-lipoxygenase (5LOX) and leukotriene A4 hydroxylase (LTA4H).
      Intracellular LTB4 levels were lower in the most aggressive cells than in cells
      with a smaller proliferation index, despite equivalent plasma levels, and lower
      expression of cytochrome P450 4F3A (CYP4F3A), one major enzyme involved in LTB4
      inactivation. Since BLT2, a LTB4 membrane receptor was also more often expressed
      on aggressive tumor cells, and since a BLT2 inhibitor significantly impaired B
      CLL viability in vitro, we propose that LTB4 was efficiently trapped onto BLT2
      present on aggressive tumors, thereby eliciting an autocrine response. Taken
      together our results demonstrate a major deregulation of the pathway leading to
      LTB4 synthesis and degradation in B-CLL cells, and provide a framework for
      understanding how these modifications promote cell survival and proliferation,
      especially in the most aggressive BCLL. 

PMID- 25072960
TI  - The soluble form of HFE protein regulates hephaestin mRNA expression in the
      duodenum through an endocytosis-dependent mechanism.
AB  - Dietary iron absorption regulation is one of the key steps for the maintenance of
      the body iron homeostasis. HFE gene expression undergoes a complex post
      transcriptional alternative splicing mechanism through which two alternative
      transcripts are originated and translated to a soluble HFE protein isoform
      (sHFE). The first purpose of this study was to determine if sHFE transcript
      levels respond to different iron conditions in duodenal and macrophage cell
      models. In addition, we aimed to determine the functional effect of the sHFE
      protein on the expression of iron metabolism-related genes in a duodenal cell
      model as well as, in vivo, in duodenum biopsy samples. Levels of sHFE transcripts
      were measured in HuTu-80, Caco-2, HT-29 and activated THP1 cells, after holo-Tf
      stimulus, and in total RNA from duodenum biopsies of functional dyspepsia
      patients. Also, the expression of several iron metabolism-related genes was
      determined after endogenous and exogenous overexpression of sHFE protein in a
      duodenal cell model. sHFE endocytosis mechanism was studied using endocytosis
      inhibitors. Our results showed that sHFE transcript expression was up-regulated
      after holo-Tf stimuli. Hephaestin and duodenal cytochrome b expressions were down
      regulated by both endogenous HFE and sHFE proteins in a duodenal cell model.
      Exogenous sHFE was able to down-regulate hephaestin mRNA levels by a clathrin
      independent, dynamin-mediated, and RhoA-regulated endocytosis mechanism.
      Moreover, HEPH levels negatively correlated with sHFE levels in the duodenum of
      functional dyspepsia patients. Thus, sHFE seems to be an important iron
      metabolism regulator playing a role in the control of dietary iron absorption in
      the duodenum. 

PMID- 25072958
TI  - A cell-type-specific role for murine Commd1 in liver inflammation.
AB  - The transcription factor NF-kappaB plays a critical role in the inflammatory
      response and it has been implicated in various diseases, including non-alcoholic
      fatty liver disease (NAFLD). Although transient NF-kappaB activation may protect
      tissues from stress, a prolonged NF-kappaB activation can have a detrimental
      effect on tissue homeostasis and therefore accurate termination is crucial.
      Copper Metabolism MURR1 Domain-containing 1 (COMMD1), a protein with functions in
      multiple pathways, has been shown to suppress NF-kappaB activity. However, its
      action in controlling liver inflammation has not yet been investigated. To
      determine the cell-type-specific contribution of Commd1 to liver inflammation, we
      used hepatocyte and myeloid-specific Commd1-deficient mice. We also used a mouse
      model of NAFLD to study low-grade chronic liver inflammation: we fed the mice a
      high fat, high cholesterol (HFC) diet, which results in hepatic lipid
      accumulation accompanied by liver inflammation. Depletion of hepatocyte Commd1
      resulted in elevated levels of the NF-kappaB transactivation subunit p65 (RelA)
      but, surprisingly, the level of liver inflammation was not aggravated. In
      contrast, deficiency of myeloid Commd1 exacerbated diet-induced liver
      inflammation. Unexpectedly we observed that hepatic and myeloid Commd1 deficiency
      in the mice both augmented hepatic lipid accumulation. The elevated levels of
      proinflammatory cytokines in myeloid Commd1-deficient mice might be responsible
      for the increased level of steatosis. This increase was not seen in hepatocyte
      Commd1-deficient mice, in which increased lipid accumulation appeared to be
      independent of inflammation. Our mouse models demonstrate a cell-type-specific
      role for Commd1 in suppressing liver inflammation and in the progression of
      NAFLD. 

PMID- 25072961
TI  - Chondroblastoma of the medial cuneiform bone in a 32-year-old woman.
AB  - Patient: Female, 32. FINAL DIAGNOSIS: Chondroblastoma. SYMPTOMS: Pain.
      MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: Oncology. OBJECTIVE: Unusual
      clinical course. BACKGROUND: 1% of all bone tumors are Chondroblastomas.
      Chondroblastomas, initially considered to be an osteoclastoma variant are benign,
      cartilaginous tumors which usually occur in the epiphysis of long bones,
      especially in the humerus, tibia, and femur, most common in children and young
      adults between the ages of 10 and 20 years. 4% of all chondroblastomas settle in
      the talus whereas cuneiform and other tarsal bones are very rare sites for the
      development of this benign chondroid lesion. CASE REPORT: A case of
      chondroblastoma involving the medial cuneiform of the left foot of a 32 year old
      woman is described. The patient presented with moderate localized pain and
      tenderness over the medial aspect of her left foot. Radiographs showed a lytic
      expansile lesion within the right cuneiform bone indicating a bone tumor. Biopsy
      demonstrated cellular areas made up of round, polygonal cells, with round-oval
      nucleus and chondroblasts that appear with a thin calcification rim.
      Intralesional curettage and synthetic bone grafting with PRP (Platelet-Rich
      Plasma) application was performed for its treatment. After 18 month follow up,
      osteointegration was observed with the defect completely filled and the patient
      was free of disease and pain. CONCLUSIONS: A painful, expansile, thin, sclerotic
      lesion detected at the cuneiform should arise suspicion for chondroblastoma even
      at age over 20 years. Meticulous curettage of the lesion from a small window with
      removal of the lesion followed by injectable phosphocalcic cement application
      with autologous PRP can be considered as a curative and technically simple
      treatment method.

PMID- 25072962
TI  - Histone deacetylase 2 controls p53 and is a critical factor in tumorigenesis.
AB  - Histone deacetylase 2 (HDAC2) regulates biological processes by deacetylation of
      histones and non-histone proteins. HDAC2 is overexpressed in numerous cancer
      types, suggesting general cancer-relevant functions of HDAC2. In human tumors the
      TP53 gene encoding p53 is frequently mutated and wild-type p53 is often disarmed.
      Molecular pathways inactivating wild-type p53 often remain to be defined and
      understood. Remarkably, current data link HDAC2 to the regulation of the tumor
      suppressor p53 by deacetylation and to the maintenance of genomic stability.
      Here, we summarize recent findings on HDAC2 overexpression in solid and
      hematopoietic cancers with a focus on mechanisms connecting HDAC2 and p53 in
      vitro and in vivo. In addition, we present an evidence-based model that
      integrates molecular pathways and feedback loops by which p53 and further
      transcription factors govern the expression and the ubiquitin-dependent
      proteasomal degradation of HDAC2 and of p53 itself. Understanding the
      interactions between p53 and HDAC2 might aid in the development of new
      therapeutic approaches against cancer. 

PMID- 25072964
TI  - The practicality or otherwise of biomedical rejuvenation therapies: a response to
      Kyriazis.
AB  - Elsewhere in this issue, Marios Kyriazis articulates a sharply skeptical
      assessment of the feasibility of medical rejuvenation, otherwise known as the
      "damage repair" approach to postponing the ill health of old age. His critique
      incorporates many errors of fact and/or interpretation and/or logic, which I
      enumerate here. I recognize that many of these errors are by no means Kyriazis's
      alone but are shared by numerous observers across the full range of biological
      expertise. It is for that reason above all that I hope this exchange will be of
      value to readers. Additionally, Kyriazis raises a number of valid concerns that
      have not been systematically addressed, by myself or by others, in past
      publications; I will attempt to remedy that here. For clarity, I will not
      structure this response as an essay, but instead as a simple point-by-point list
      of comments concerning individual statements and inferences that Kyriazis makes.

PMID- 25072965
TI  - A super intramolecular self-enhanced electrochemiluminescence immunosensor based
      on polymer chains grafted on palladium nanocages.
AB  - An intramolecular self-enhanced electrochemiluminescent derivative is prepared by
      grafting polystyrene (PS)-based polymer chains with pendant Ru(ii) luminophore
      from poly(ethylenimine) (PEI) on the surface of palladium nanocages (PdNCs). In
      this way, the Ru(ii) luminophore and its co-reactive group (amine groups in PEI)
      exist in the same polymer molecule, which shortens the electronic transmission
      distance between them and enhances the luminous stability. Meanwhile, through
      atom transfer radical polymerization (ATRP), the loading amount of Ru(ii)
      luminophore is greatly increased. Therefore, the obtained electrochemiluminescent
      derivative (PdNC-PEI-PSRu) has high luminous efficiency and stability.
      Furthermore, due to their special nanostructures of porous walls and hollow
      interiors, PdNCs have great advantages in high specific surface areas and good
      electrocatalytic ability, which make them act as an excellent immobilized
      platform for PEI and detection antibody. Based on the sandwiched immunoreactions,
      a sensitive "signal on" electrochemiluminescence immunosensor is constructed for
      the detection of carbohydrate antigen 15-3 (CA 15-3). As a result, a wide linear
      range from 0.01 U mL(-1) to 120 U mL(-1) is acquired with a relatively low
      detection limit of 0.003 U mL(-1). 

PMID- 25072966
TI  - Chemically integrated two-dimensional hybrid zinc manganate/graphene nanosheets
      with enhanced lithium storage capability.
AB  - Hybrid inorganic/graphene two-dimensional (2D) nanostructures can offer vastly
      open large surface areas for ion transport and storage and enhanced electron
      transport, representing a promising material platform for next-generation energy
      storage. Here we report chemically integrated hybrid ZnMn2O4/graphene nanosheets
      synthesized via a facile two-step method for greatly enhanced lithium storage
      capability. The hybrid 2D nanosheets are composed of ultrafine ZnMn2O4
      nanocrystals with a mean diameter of ~4 nm attached to and well dispersed on the
      surface of reduced graphene oxide sheets. The hybrid nanosheets based anode
      offers a high capacity of ~800 mAh g(-1) at a current rate of 500 mA g(-1),
      excellent rate capability, and long-term cyclability with reversible capacity of
      ~650 mAh g(-1) over 1500 cycles at a current density of 2000 mA g(-1). Moreover,
      when tested in a temperature range of ~0-60  degrees C, the designed anode can
      maintain high discharge capacities from 570 to 820 mAh g(-1).

PMID- 25072967
TI  - Experimental demonstration of delayed-choice decoherence suppression.
AB  - Wheeler's delayed-choice experiment illustrates vividly that the observer plays a
      central role in quantum physics by demonstrating that complementarity or wave
      particle duality can be enforced even after the photon has already entered the
      interferometer. The delayed-choice quantum eraser experiment further demonstrates
      that complementarity can be enforced even after detection of a quantum system,
      elucidating the foundational nature of complementarity in quantum physics.
      However, the applicability of the delayed-choice method for practical quantum
      information protocols continues to be an open question. Here, we introduce and
      experimentally demonstrate the delayed-choice decoherence suppression protocol,
      in which the decision to suppress decoherence on an entangled two-qubit state is
      delayed until after the decoherence and even after the detection of a qubit. Our
      result suggests a new way to tackle Markovian decoherence in a delayed manner,
      applicable for practical entanglement distribution over a dissipative channel. 

PMID- 25072968
TI  - Fluorination of graphene enhances friction due to increased corrugation.
AB  - The addition of a single sheet of carbon atoms in the form of graphene can
      drastically alter friction between a nanoscale probe tip and a surface. Here, for
      the first time we show that friction can be altered over a wide range by
      fluorination. Specifically, the friction force between silicon atomic force
      microscopy tips and monolayer fluorinated graphene can range from 5-9 times
      higher than for graphene. While consistent with previous reports, the combined
      interpretation from our experiments and molecular dynamics simulations allows us
      to propose a novel mechanism: that the dramatic friction enhancement results from
      increased corrugation of the interfacial potential due to the strong local charge
      concentrated at fluorine sites, consistent with the Prandtl-Tomlinson model. The
      monotonic increase of friction with fluorination in experiments also demonstrates
      that friction force measurements provide a sensitive local probe of the degree of
      fluorination. Additionally, we found a transition from ordered to disordered
      atomic stick-slip upon fluorination, suggesting that fluorination proceeds in a
      spatially random manner. 

PMID- 25072963
TI  - NFAT as cancer target: mission possible?
AB  - The NFAT signaling pathway regulates various aspects of cellular functions; NFAT
      acts as a calcium sensor, integrating calcium signaling with other pathways
      involved in development and growth, immune response, and inflammatory response.
      The NFAT family of transcription factors regulates diverse cellular functions
      such as cell survival, proliferation, migration, invasion, and angiogenesis. The
      NFAT isoforms are constitutively activated and overexpressed in several cancer
      types wherein they transactivate downstream targets that play important roles in
      cancer development and progression. Though the NFAT family has been conclusively
      proved to be pivotal in cancer progression, the different isoforms play distinct
      roles in different cellular contexts. In this review, our discussion is focused
      on the mechanisms that drive the activation of various NFAT isoforms in cancer.
      Additionally, we analyze the potential of NFAT as a valid target for cancer
      prevention and therapy. 

PMID- 25072969
TI  - The "in situ molding technique: " an accurate and simple way to fix resorbable
      plates to the facial skeleton.
AB  - Bioabsorbable plates developed for use in the facial skeleton have become an
      integral part of the craniomaxillofacial surgeon's reconstructive armamentarium.
      They avoid the problems associated with the retention of metal plates and can be
      easily contoured when heated in a thermobath. The technical process of molding
      and securing these devices, often through small access incisions, to achieve
      rigid fixation of facial fractures can be difficult. In this article, we describe
      a simple, novel technique that we have developed, using hot water suction
      irrigation, to achieve in situ molding of resorbable plates during facial
      fracture fixation. We used this technique to fix 123 facial fractures in 110
      patients over a 4-year period. No complications secondary to the use of hot water
      suction irrigation were encountered. 

PMID- 25072971
TI  - Temporomandibular joint disorder and inner ear pruritus: resolution by
      eminectomy.
AB  - Recurrent dislocation of the temporomandibular joint (TMJ) disk is caused by many
      factors. Dislocation can result in an acute or chronic closed lock condition.
      Temporomandibular joint dysfunction is often presented with otalgia symptoms.
      Other aural symptoms such as deafness, tinnitus, pressure/blockage, and vertigo
      are also commonly presented together with TMJ dysfunction (Clin Otolaryngol
      Allied Sci. 1980;5:23-36). However, pruritus associated with TMJ dysfunction in
      the inner ear has never been reported in the literature. We report a case history
      of TMJ dysfunction and associated inner ear pruritus, which are both resolved by
      eminectomy. 

PMID- 25072972
TI  - Three-dimensional analysis of facial morphology.
AB  - OBJECTIVES: The objectives of this study were to evaluate sexual dimorphism for
      facial features within Chinese and African American populations and to compare
      the facial morphology by sex between these 2 populations. MATERIALS AND METHODS:
      Three-dimensional facial images were acquired by using the portable 3dMDface
      System, which captured 189 subjects from 2 population groups of Chinese (n = 72)
      and African American (n = 117). Each population was categorized into male and
      female groups for evaluation. All subjects in the groups were aged between 18 and
      30 years and had no apparent facial anomalies. A total of 23 anthropometric
      landmarks were identified on the three-dimensional faces of each subject. Twenty
      one measurements in 4 regions, including 19 distances and 2 angles, were not only
      calculated but also compared within and between the Chinese and African American
      populations. The Student's t-test was used to analyze each data set obtained
      within each subgroup. RESULTS: Distinct facial differences were presented between
      the examined subgroups. When comparing the sex differences of facial morphology
      in the Chinese population, significant differences were noted in 71.43% of the
      parameters calculated, and the same proportion was found in the African American
      group. The facial morphologic differences between the Chinese and African
      American populations were evaluated by sex. The proportion of significant
      differences in the parameters calculated was 90.48% for females and 95.24% for
      males between the 2 populations. The African American population had a more
      convex profile and greater face width than those of the Chinese population.
      CONCLUSIONS: Sexual dimorphism for facial features was presented in both the
      Chinese and African American populations. In addition, there were significant
      differences in facial morphology between these 2 populations.

PMID- 25072973
TI  - Cleft lip and/or palate: one organization's experience with more than a quarter
      million surgeries during the past decade.
AB  - BACKGROUND: A charitable surgical relief organization (Smile Train) enables local
      physicians in developing countries to provide surgical treatment of cleft lip
      and/or palate. The following study reviews the epidemiological data from more
      than 260,000 surgeries performed in India through this organization from 2000
      until January 1, 2012. METHODS: Demographic and clinical patient data were
      collected from the participating surgeons, recorded in Excel (Microsoft, Redmond,
      WA), and analyzed using Software Package for the Social Sciences (IBM, Armonk,
      NY). RESULTS: The distribution of clefts treated was 20.2% of cleft lip, 13.9% of
      cleft palate (CP), and 65.9% of cleft lip and palate. The overall unilateral
      bilateral ratio was 2.49:1 with a left-right ratio of 2.03:1. The male-female
      ratio was 1.58:1. Of the total patients, 2.67% had associated anomalies. The most
      frequently performed surgeries included primary repair of a unilateral cleft lip
      (41.62%), followed by primary repair of a CP (31.15%). The mean age at surgery
      was 7.91 years. The reported complication rate was 0.88%. CONCLUSIONS: The data
      collected are from the largest reported cohort of orofacial cleft patients in
      India. The cleft type, sex distribution, and overall male predominance resemble
      previously reported distributions; however, fewer CP patients and greater cleft
      lip and palate patients presented than would be expected. The frequency of
      associated anomalies was lower than in previous reports. Although there is
      significant selection bias to milder cases from lower socioeconomic groups in
      this study, the large sample size is unique, and the data collected can provide a
      valuable framework to further study the epidemiology of cleft lip and/or palate
      in India.

PMID- 25072974
TI  - Evaluation of the changes in the nasal cavity during the migraine attack.
AB  - OBJECTIVES: There are some subjective symptoms involving the nasal cavity such as
      nasal congestion during a migraine attack. In this study, we aimed to evaluate
      the possible changes occurring in the nasal cavity during headache in patients
      with migraine. MATERIALS AND METHODS: Patients with migraine were studied. The
      control group consisted of patients with tension-type headache. The severity of
      the headache and accompanying complaints were assessed using visual analog scale,
      and the nasal mucosa was assessed through anterior rhinoscopy and endoscopy.
      Resistance of the nasal cavity was evaluated through anterior rhinomanometry.
      Data obtained during the attack periods and attack-free periods were compared.
      RESULTS: Twenty-five patients with migraine and 15 patients with tension-type
      headache were enrolled. It was found that 19 patients (76%) of the group with
      migraine and 5 patients of the group with tension-type headache were experiencing
      nasal congestion during the attack and that the differences between the groups
      were statistically significant (P < 0.05). The average of total nasal resistance
      in the patients with migraine was 0.57 +/- 0.60 kPa/L/sn during migraine attacks
      and 0.28 +/- 0.14 kPa/L/sn during attack-free periods. The average of total nasal
      resistance in the patients with tension-type headache was 0.32 +/- 0.14 kPa/L/sn
      during attack periods and 0.31 +/- 0.20 kPa/L/sn during attack-free periods. In
      the group with migraine, the change of nasal resistance between during the attack
      and attack-free periods was found statistically significant, whereas there was no
      statistically significant difference in the group with tension-type headache.
      CONCLUSIONS: According to the results of this study, complaints regarding nasal
      obstruction and nasal airway resistance increase during migraine attacks. Cause
      and-effect relationship between nasal obstruction and pain is not clear, and
      clinical trials are needed to determine the effect of nasal obstruction treatment
      (mucosal decongestion, etc) on the complaint of pain.

PMID- 25072975
TI  - Congenital muscular torticollis in older children: treatment with Z-plasty
      technique.
AB  - Congenital muscular torticollis (CMT) is a common congenital disorder of the
      musculoskeletal system in neonates and infants. The aim of this study was to
      evaluate the results of inferior Z-plasty in older children with CMT. They had
      mean age of 10 years (range, 5-14 years) and were followed up for 1 to 6 years.
      Postoperative protocol included a neck exercise program composed of active and
      passive movements in all cases and immobilization with a cervical collar in only
      4 patients. This study concluded that surgical management of older children with
      CMT using Z-lengthening gives excellent clinical and functional results. The
      procedure is much more effective than other techniques and relatively
      complication-free and safe. Postoperative cervical collar and a well-planed
      physiotherapy protocol go a long way toward ensuring good to excellent results.
      Early diagnosis and treatment are necessary for good results. 

PMID- 25072976
TI  - Early pressure dressing for the prevention of subdural effusion secondary to
      decompressive craniectomy in patients with severe traumatic brain injury.
AB  - This study was performed to investigate the effect of early pressure dressing on
      the prevention of postoperative subdural effusion secondary to decompressive
      craniectomy (DC) in patients with severe traumatic brain injury (STBI). Patients
      with STBI who had undergone DC for refractory increased intracranial pressure
      between January 2008 and December 2011 (n = 169) were randomly divided into early
      pressure dressing (n = 82) and control (n = 87) groups. Early pressure dressing
      with an elastic bandage or general wrapping (control treatment) was applied 7 to
      10 days after DC. Patients' age, sex, preoperative Glasgow Coma Scale score,
      incidence rate of subdural effusion, hospitalization time, and postoperative
      Glasgow Outcome Scale score were compared between groups. Intracranial pressure
      was measured immediately before and on the day after pressure dressing. No
      significant difference in age, sex, preoperative Glasgow Coma Scale score, or
      postoperative Glasgow Outcome Scale score was observed between groups (P > 0.05).
      Subdural effusion incidence rates were significantly lower in the early pressure
      dressing group than those in the control group (chi2 = 5.449, P = 0.021), and a
      larger proportion of patients in the early pressure dressing group was
      hospitalized for 30 days or less (chi2 = 5.245, P = 0.027). Early pressure
      dressing 7 to 10 days after DC, which is a noninvasive, simple procedure, reduced
      the incidence rate of subdural effusion and shortened hospitalization time after
      DC for STBI.

PMID- 25072977
TI  - Update on the surgical management of temporomandibular joint-centered tendon
      sheath giant cell tumor with intradural extension: introducing a cost-effective
      method in using temporal bone for skull base reconstruction in preventing brain
      hernia.
AB  - Tendon sheath giant cell tumor is an idiopathic proliferative and destructive
      disease of the synovium. It is rare and tends to arise in large joints, for
      example, knee and ankle, but it can also arise in temporomandibular joints
      (TMJs). Because of its destructive nature, immediate treatment upon diagnosis is
      recommended. Radical resection proved to be an excellent choice for superior
      local control. However, the unfavorable anatomic location of TMJ and
      infratemporal fossa tumor with intradural extension make such a resection
      impractical. Hereby, we reported a case of resection of a TMJ tendon sheath giant
      cell tumor with intradural extension using a transcranial approach. This involves
      a complex radical resection with subsequent reconstruction. Transposition of
      temporal bone flap is a novel state-of-the-art technique in reconstructing the
      middle fossa floor defect by providing a three-dimensional rigid architecture to
      support the brain. Temporal bone flap is a reliable plug for rigid support in
      preventing brain hernia and cerebrospinal fluid leak. Despite its complexity,
      this cost-effective technique is relatively straightforward to learn and is
      applicable across all socioeconomic groups. 

PMID- 25072978
TI  - Morphologic measure of retrosigmoid approach using volume rendering with thin
      section computed tomography.
AB  - OBJECTIVE: The objective of this study was to research the jugular foramen,
      internal auditory pore, and the turning point between its components using
      imageological methods and provide theoretical basis for retrosigmoid approach.
      METHODS: A total of 100 cases of adult hip computed tomographic scans were
      reconstructed. alpha, beta, AC, AB, BC, and the shortest distance were measured.
      RESULTS: The angle alpha was measured as 39.50 (4.74) degrees (range, 29.3-48.5
      degrees; 95% confidence interval [CI], 38.64-40.35 degrees). The angle beta was
      measured as 46.35 (5.51) degrees (range, 31.09-64.74 degrees; 95% CI, 45.35-47.35
      degrees). The distance of AC was measured as 44.94 (3.84) mm (range, 34.9-54.9
      mm; 95% CI, 44.25-45.64 mm). The distance of AB was measured as 43.68 (4.56) mm
      (range, 33.8-54.7 mm; 95% CI, 42.86-44.51 mm). The distance of BC was measured as
      6.15 (2.04) mm (range, 2.7-14.7 mm; 95% CI, 5.78-6.52 mm). The safe distance was
      measured as 5.21 (0.23) mm (range, 0.84-12.92 mm; 95% CI, 5.17-5.25 mm).
      CONCLUSIONS: These previously mentioned results can help to locate these
      structures in the measurement plane and provide reference for surgery.

PMID- 25072979
TI  - Reconstruction of the lower vermilion with a musculomucosal flap from the upper
      lip in the repair of extensive lower lip and chin defects.
AB  - In the repair of extensive lower lip and chin defects, the reconstruction of
      vermilion at the same time is a great challenge to plastic surgeons. We describe
      a novel method for the reconstruction of lower vermilion with musculomucosal flap
      from the upper lip in the repair of extensive lower lip and chin defects. Two
      patients underwent extensive lower lip and chin reconstruction together with
      vermilion reconstruction. This technique used 3 basic components: musculomucosal
      flap from the upper lip, buccal mucosal advancement flap, and cutaneous
      rotational flap from the neck. All the flaps survived without significant
      complications. Labial function in the motions of expression and speaking was
      maintained. The patients could basically close their mouths completely, and there
      were no drooping or small-mouth deformities postoperatively. Functional and
      cosmetically acceptable lower-lip and chin reconstructions in both patients were
      achieved. 

PMID- 25072980
TI  - Plasma carotenoids and retinol and overall and breast cancer risk: a nested case
      control study.
AB  - Experimental studies suggest that carotenoids and retinol may play a role in
      carcinogenesis, but epidemiological evidence is lacking. We investigated the
      prospective associations between plasma concentrations of major carotenoids and
      retinol, and overall and breast cancer risk. A nested case-control study included
      all first incident cancer cases diagnosed in the SU.VI.MAX cohort between 1994
      and 2002 (n = 159 cases, 1 matched control/case). Baseline plasma concentrations
      of carotenoids and retinol were measured by high-performance liquid
      chromatography. Conditional logistic regression was used to assess odds ratios
      for an increase of 0.1 MUmol/L [odds ratio (OR)] and 95% confidence intervals
      (CI). Plasma beta-carotene (OR = 0.95, 95% CI = 0.90-0.99, Ptrend = 0.04) and
      beta-cryptoxanthin concentrations (OR = 0.89, 95% CI = 0.81-0.99, Ptrend = 0.03)
      were inversely associated with overall cancer risk. Plasma beta-cryptoxanthin
      concentration was inversely associated with breast cancer risk (OR = 0.83, 95% CI
      = 0.71-0.96, Ptrend = 0.02). The OR between plasma lycopene concentration and
      overall cancer risk was 1.07 (0.99-1.15), Ptrend = 0.06. This association turned
      significant (Ptrend = 0.01) when excluding cancer cases diagnosed during the
      first year of follow-up. This prospective study suggests an inverse association
      between plasma concentrations of beta-cryptoxanthin and both overall and breast
      cancer risk, and an inverse association between beta-carotene and overall cancer
      risk. The direct association between lycopene concentration and cancer risk
      deserves further investigation. 

PMID- 25072981
TI  - Poking cells for efficient vector-free intracellular delivery.
AB  - Techniques for introducing foreign molecules and materials into living cells are
      of great value in cell biology research. A major barrier for intracellular
      delivery is to cross the cell membrane. Here we demonstrate a novel platform
      utilizing diamond nanoneedle arrays to facilitate efficient vector-free cytosolic
      delivery. Using our technique, cellular membrane is deformed by an array of
      nanoneedles with a force on the order of a few nanonewtons. We show that this
      technique is applicable to deliver a broad range of molecules and materials into
      different types of cells, including primary neurons in adherent culture.
      Especially, for delivering plasmid DNAs into neurons, our technique produces at
      least eightfold improvement (~45% versus ~1-5%) in transfection efficiency with a
      dramatically shorter experimental protocol, when compared with the commonly used
      lipofection approach. It is anticipated that our technique will greatly benefit
      basic research in cell biology and also a wide variety of clinical applications. 

PMID- 25072982
TI  - Hormones, behavior, and social network analysis: exploring associations between
      cortisol, testosterone, and network structure.
AB  - We used a new interdisciplinary paradigm of social network analysis (SNA) to
      investigate associations between hormones and social network structures. We
      examine these biobehavioral processes and test hypotheses about how hormones are
      associated with social network structures using exponential random graph modeling
      (ERGM) in a cohort of first-year students (n=74; 93% female; M age=27 years) from
      a highly competitive, accelerated nursing program. Participants completed
      friendship nominations and as a group simultaneously donated saliva (later
      assayed for cortisol and testosterone). ERGM analyses revealed that salivary
      cortisol levels were inversely associated with the number of outgoing ties (i.e.,
      network activity). By contrast, testosterone was not related to friendship
      network structure. Integration of SNA and salivary bioscience creates a novel
      approach to understanding hormone-behavior relationships within the context of
      human social ecologies.

PMID- 25072983
TI  - Dynamics and drivers of hantavirus prevalence in rodent populations.
AB  - Human encroachment on wildlife habitats has contributed to the emergence of
      several zoonoses. Pathogenic hantaviruses are hosted by rodents and cause severe
      diseases in the Americas and Eurasia. We reviewed several factors that
      potentially drive prevalence (the proportion of infected rodents) in host
      populations. These include demography, behavior, host density, small mammal
      diversity, predation, and habitat and landscape characteristics. This review is
      the first to include a quantitative summary of the literature investigating
      hantavirus prevalence in rodents. Demographic structure and density were
      investigated the most and predation the least. Reported effects of demographic
      structure and small mammal diversity were consistent, whereby reproductive males
      were most likely to be infected and prevalence decreased with small mammal
      diversity. The influences of habitat and landscape properties are often complex
      and indirect. The relationship between density and prevalence merits more
      investigation. Most hantavirus hosts are habitat generalists and their control is
      challenging. Incorporating all potential factors and their interactions is
      essential to understanding and controlling infection in host populations.

PMID- 25072984
TI  - Antibodies reactive to Ehrlichia spp. are common in Oklahoma horses.
AB  - Abstract Tick infestations and infection with tick-borne agents are commonly
      recognized in horses in North America, but equine infection with true Ehrlichia
      spp. has not been described. To determine the degree to which horses in the south
      central United States are naturally exposed to and infected with tick-borne
      disease agents, serum samples were collected at random (n=240) or from horses
      with active tick infestations (n=73) and tested by immunofluorescence antibody
      assay (IFA) and/or enzyme-linked immunosorbent assay (ELISA) for evidence of
      antibodies reactive to Ehrlichia spp., Anaplasma spp., and Borrelia burgdorferi.
      Positive samples were further evaluated by species-specific serology for
      antibodies reactive to E. canis and E. chaffeensis, and whole blood samples were
      tested by PCR for evidence of infection with E. canis, E. chaffeensis, E.
      ewingii, and an E. ruminantium-like organism referred to as the Panola Mountain
      Ehrlichia. Antibodies reactive to Ehrlichia spp. were identified in 8.75%
      (21/240) of the randomly acquired samples and 24.7% (18/73) of the serum samples
      from tick-infested horses, but species-specific ELISA and PCR failed to confirm
      exposure to or infection with any known Ehrlichia spp. Antibodies to Anaplasma
      spp. (5/313; 1.6%) and B. burgdorferi (3/313; 1.0%) were uncommon. These data
      suggest that horses in the south-central United States are likely exposed to a
      novel Ehrlichia sp. Further research is needed to identify the etiologic agent
      responsible for the serologic activity seen and to determine the clinical
      significance, if any, of this finding. 

PMID- 25072985
TI  - "Rickettsia amblyommii" induces cross protection against lethal Rocky Mountain
      spotted fever in a guinea pig model.
AB  - Rocky Mountain spotted fever (RMSF) is a severe illness caused by Rickettsia
      rickettsii for which there is no available vaccine. We hypothesize that exposure
      to the highly prevalent, relatively nonpathogenic "Rickettsia amblyommii"
      protects against R. rickettsii challenge. To test this hypothesis, guinea pigs
      were inoculated with "R. amblyommii." After inoculation, the animals showed no
      signs of illness. When later challenged with lethal doses of R. rickettsii, those
      previously exposed to "R. amblyommii" remained well, whereas unimmunized controls
      developed severe illness and died. We conclude that "R. amblyommii" induces an
      immune response that protects from illness and death in the guinea pig model of
      RMSF. These results provide a basis for exploring the use of low-virulence
      rickettsiae as a platform to develop live attenuated vaccine candidates to
      prevent severe rickettsioses.

PMID- 25072986
TI  - Detection of Bartonella species in the blood of veterinarians and veterinary
      technicians: a newly recognized occupational hazard?
AB  - BACKGROUND: Bartonella species are important emerging pathogens in human and
      veterinary medicine. In the context of their daily activities, veterinary
      professionals have frequent animal contact and arthropod exposures. Detection of
      Bartonella spp. using traditional culture methods has been limited by poor
      sensitivity, making it difficult to determine the prevalence of infection in this
      population. We have developed a detection method combining enrichment culture and
      molecular amplification, which increases testing sensitivity. METHODS: We
      performed a cross-sectional study to determine the prevalence of detectable
      Bartonella spp. in the blood of veterinary personnel and nonveterinary control
      subjects. Bartonella was detected by enrichment blood culture with conventional
      PCR followed by DNA sequencing. RESULTS were correlated with epidemiological
      variables and symptoms. RESULTS: We detected DNA from at least one Bartonella
      species in 32 (28%) of the 114 veterinary subjects. After DNA sequencing, the
      Bartonella species could be determined for 27 of the 32 infected subjects,
      including B. henselae in 15 (56%), B. vinsonii subsp. berkhoffii in seven (26%),
      B. koehlerae in six (22%), and a B. volans-like sequence in one (4%). Seventy
      percent of Bartonella-positive subjects described headache compared with 40% of
      uninfected veterinarians (p=0.009). Irritability was also reported more commonly
      by infected subjects (68% vs. 43%, p=0.04). CONCLUSIONS: Our study supports an
      emerging body of evidence that cryptic Bartonella bloodstream infection may be
      more frequent in humans than previously recognized and may induce symptoms.
      Longitudinal studies are needed to determine the natural course and clinical
      features of Bartonella infection.

PMID- 25072987
TI  - Evaluation of clinical and sonographic features in 55 children with tularemia.
AB  - AIM: The aim of this study was to determine the clinical characteristics and
      sonographic features of lymphadenopathy (LAP) and to evaluate the treatment
      modalities and treatment outcomes in children with tularemia. MATERIALS AND
      METHODS: Demographic characteristics, ultrasonographic and physical examination
      findings, and treatment outcomes in 55 tularemia patients (24 male and 31 female)
      with a mean age of 10.8 +/- 4.0 years were analyzed retrospectively. Lymph node
      necrosis was classified in three stages based on ultrasound findings-stage 1,
      cortical microabscesses; stage 2, cortical and medullar abscesses; stage 3, total
      necrosis of the lymph node. RESULTS: In total, 50 (90%) of the patients had
      oropharyngeal, four (8%) had glandular, and one (2%) had oculoglandular
      tularemia. The most common symptoms were sore throat (67%) and fever (64%). LAP
      was the most frequently (100%) observed sign. Abscess formation was noted in 36
      (65%) patients, of which seven (19%) were sonographically classified as stage 1,
      20 (55%) as stage 2, and nine (26%) as stage 3. There was a statistically
      significant correlation between delayed treatment and stage of abscess formation
      in lymph nodes (p<0.05). Treatment failure was observed in 24 (44%) patients.
      There was no significant correlation between treatment regimen and treatment
      failure (p>0.05). In all, nine (16%) of the patients did not respond to medical
      treatment, and surgical intervention was required. CONCLUSION: Tularemia should
      be considered in the differential diagnosis of children presenting with
      unexplained fever, sore throat, and cervical LAP in endemic areas. Sonographic
      findings may be useful in the evaluation and staging of this infection.

PMID- 25072988
TI  - The necrophagous fly anthrax transmission pathway: empirical and genetic evidence
      from wildlife epizootics.
AB  - Early studies confirmed Bacillus anthracis in emesis and feces of flies under
      laboratory conditions, but there is little empirical field evidence supporting
      the roles of flies in anthrax transmission. We collected samples during outbreaks
      of anthrax affecting livestock and native and exotic wildlife on two ranches in
      West Texas (2009-2010). Sampling included animal carcasses, maggots, adult flies
      feeding on or within several meters of carcasses, and leaves from surrounding
      vegetation. Microbiology and PCR were used to detect B. anthracis in the samples.
      Viable B. anthracis and/or PCR-positive results were obtained from all
      represented sample types. Genetic analysis of B. anthracis samples using
      multilocus variable number tandem repeat analysis (MLVA) confirmed that each
      ranch represented a distinct genetic lineage. Within each ranch, we detected the
      same genotype of B. anthracis from carcasses, maggots, and adult flies. The
      results of this study provide evidence supporting a transmission cycle in which
      blowflies contaminate vegetation near carcasses that may then infect additional
      browsing animals during anthrax outbreaks in the shrubland environment of West
      Texas.

PMID- 25072989
TI  - Broad-range survey of tick-borne pathogens in Southern Germany reveals a high
      prevalence of Babesia microti and a diversity of other tick-borne pathogens.
AB  - Abstract Ticks harbor numerous pathogens of significance to human and animal
      health. A better understanding of the pathogens carried by ticks in a given
      geographic area can alert health care providers of specific health risks leading
      to better diagnosis and treatments. In this study, we tested 226 Ixodes ricinis
      ticks from Southern Germany using a broad-range PCR and electrospray ionization
      mass spectrometry assay (PCR/ESI-MS) designed to identify tick-borne bacterial
      and protozoan pathogens in a single test. We found 21.2% of the ticks tested
      carried Borrelia burgdorferi sensu lato consisting of diverse genospecies; a
      surprisingly high percentage of ticks were infected with Babesia microti (3.5%).
      Other organisms found included Borrelia miyamotoi, Rickettsia helvetica,
      Rickettsia monacensis, and Anaplasma phagocytophilum. Of further significance was
      our finding that more than 7% of ticks were infected with more than one pathogen
      or putative pathogen. 

PMID- 25072990
TI  - Zoonotic disease in a peripheral population: persistence and transmission of
      Leishmania major in a putative sink-source system in the Negev Highlands, Israel.
AB  - Populations at the edge of their geographic distributions are referred to as
      peripheral populations. Very little attention has been given to this topic in the
      context of persistence of infectious disease in natural populations. In this
      study, we examined this question using zoonotic cutaneous leishmaniasis (ZCL)
      caused by Leishmania major in the Negev Desert of Israel as a model system. Here,
      we suggest that the regional persistence of Phlebotomus papatasi populations and
      L. major transmission in the Sede Boqer region could be explained through
      processes akin to sink-source and/or mainland-island metapopulation dynamics.
      Given its potentially enzootically superior ecological conditions, we hypothesize
      that the Zin Valley ecotope constitutes the "mainland" or the "source" patch for
      the Sede Boqer area where L. major transmission is persistent and resistant to
      local extinctions (die-outs) whereas the local sand fly populations on the Zin
      Plateau ("island patch" or "sink patch") are more prone to local extinctions.
      Between 2007 and 2008, we trapped sand flies and sand rats in the two areas and
      compared sand fly abundance and L. major infection prevalence in both. In both
      2007 and 2008, sand fly abundance was high and continuous in the Zin Wadi but low
      and discontinuous in the Zin Plateau. Infection prevalence of sand rats was
      significantly higher in the Wadi (13%) compared with the Zin Plateau (3%).
      Minimum infection rate in sand flies did not differ significantly between the two
      areas. Overall, our results are consistent with the premise that the Zin Valley
      population is relatively robust in terms of L. major transmission, whereas
      transmission is potentially more tenuous in the plateau. Understanding the biotic
      and abiotic processes enabling the persistence of L. major and other vector-borne
      diseases in peripheral disease foci is important for predicting the effect of
      anthropogenic land use and climate change.

PMID- 25072991
TI  - Is ribavirin prophylaxis effective for nosocomial transmission of Crimean-Congo
      hemorrhagic fever?
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonotic disease that is
      transmitted primarily through contact with ticks. Nosocomial cases and outbreaks
      of CCHF have been reported from many countries. Health care workers (HCWs) are at
      risk of exposure to CCHF. In our study, we evaluated seven HCWs' exposure to
      confirmed CCHF patients' infected blood and body fluids and prophylactic efficacy
      of the ribavirin on nosocomial transmission of CCHF retrospectively. Between 2007
      and 2013, 150 CCHF cases were admitted to our clinic. During the follow-up of
      these patients, four doctors and three nurses had contact with infected blood and
      body fluids through needle stick injury, contact of skin and mucosal surfaces,
      and probable aerosolization. All of the index cases' diagnoses of CCHF were
      confirmed during the contact. Ribavirin prophylaxis was administered within 0.5-1
      h in six out of seven cases. All of these cases' CCHF virus PCR results were
      negative. One physician had no contact with infected blood or body fluid, so
      ribavirin prophylaxis was not administered. The physician developed CCHF and
      diagnosis was confirmed. Although efficacy of ribavirin for prophylaxis is not
      clear and very few data exist on prophylactic usage of ribavirin, lack of
      clinical manifestations in our cases that were given ribavirin compared with the
      developed clinical manifestations in the physician may be explained by the
      prophylactic efficacy of the ribavirin.

PMID- 25072992
TI  - Reproductive biology and susceptibility of Florida Culex coronator to infection
      with West Nile virus.
AB  - Abstract Ornithophilic Culex species are considered the primary amplification
      vectors of West Nile virus (WNV) in bird hosts as well as vectors responsible for
      epidemic transmission. Culex coronator was first collected from Okaloosa, Santa
      Rosa, Walton, and Washington Counties in Florida in 2005 and has since spread
      throughout the state. The vector competence of Cx. coronator for WNV, known to be
      infected in nature, has not been assessed. Without this knowledge, we are unable
      to assess this species' potential as an enzootic and epidemic vector of WNV in
      Florida. In the current study, we investigate the reproductive biology and
      susceptibility to WNV infection, dissemination, and transmission by Cx.
      coronator. We show that Cx. coronator is capable of delaying oviposition for
      several weeks after blood feeding and that the number of eggs laid is greater for
      avian than mammalian hosts. Cx. coronator were highly susceptible to infection
      (~80-100%) and dissemination (~65-85% by 18 days since exposure) with lower rates
      of transmission (0-17% at 25 degrees C and 28-67% at 28 degrees C), suggesting
      that it is a competent vector of WNV under some conditions. The proportion of
      mosquitoes with disseminated infections related to the time since exposure and
      was higher at 28 degrees C than at 25 degrees C. The rapid and statewide
      distribution of Cx. coronator throughout Florida poses as a potential public
      health risk. This baseline knowledge is essential information for mosquito
      control and public health agencies to assess current and future disease risk to
      Southeastern United States. 

PMID- 25072993
TI  - Anthrax in a backyard domestic dog in Ukraine: a case report.
AB  - Anthrax has been reported in domestic and wild dogs throughout much of the world.
      Generally, canids are considered resistant to anthrax, although there are several
      reports of anthrax deaths in both wild and domestic canid populations. Prior to
      2012, anthrax had not been reported in dogs in Ukraine, despite a long history in
      livestock and wildlife. An outbreak involving at least one cow and one dog was
      reported from a backyard setting in southern Ukraine in August of 2012.
      Laboratory results and epizootic data were compiled from official investigation
      reports of regional and state veterinary services involved in the case response.
      A single dog died after being fed meat and bones from an illegally slaughtered
      heifer that died of anthrax 5 days earlier. On the evening of the dog's death,
      the dog refused food or water; however, there were no other clinical signs.
      Laboratory tests of dog tissue included traditional bacteriology for Bacillus
      anthracis, a small rodent bioassay for virulence, and immunoprecipitation tests
      (IPT). IPT was positive, viable B. anthracis colonies were cultured, and a
      bioassay confirmed virulence. This was the first confirmed case of canid anthrax
      in Ukraine. This case report serves to remind veterinary officials that anthrax
      can affect a wide number of species. We advise surveillance systems remain
      flexible and include animals that might not otherwise be tested.

PMID- 25072994
TI  - Serological anthrax surveillance in wild boar (Sus scrofa) in Ukraine.
AB  - Anthrax, caused by Bacillus anthracis, is an acute disease affecting wildlife,
      livestock, and humans worldwide, although its impact on these populations is
      underappreciated. In Ukraine, surveillance is passive, and anthrax is often
      detected in livestock. However, wildlife is not subject to surveillance, although
      anthrax deaths (such as in wild boar, Sus scrofa) have been documented. The wild
      boar is a plentiful and widespread species in Ukraine and is frequently hunted.
      We initiated a screening study testing Ukrainian wild boar blood samples for
      antibodies to B. anthracis. We mapped results relative to known livestock anthrax
      hotspots. We discovered evidence of exposure in wild boar up to 35 km from
      livestock anthrax hotspots and over 400 km from previous anthrax reports in
      boars. We make recommendations about using wildlife species as biosentinels for
      anthrax in Ukraine.

PMID- 25072995
TI  - Molecular detection and phylogenetic analysis of tick-borne encephalitis virus in
      rodents captured in the transdanubian region of Hungary.
AB  - Abstract Tick-borne encephalitis virus (TBEV) infection is a common zoonotic
      disease affecting humans in Europe and Asia. To determine whether TBEV is present
      in small mammalian hosts in Hungary, liver samples of wild rodents were tested
      for TBEV RNA. Over a period of 7 years, a total of 405 rodents were collected at
      five different geographic locations of the Transdanubian region. TBEV nucleic
      acid was identified in four rodent species: Apodemus agrarius, A. flavicollis,
      Microtus arvalis, and Myodes glareolus. Out of the 405 collected rodents, 17
      small mammals (4.2%) were positive for TBEV. The present study provides molecular
      evidence and sequence data of TBEV from rodents in Hungary. 

PMID- 25072996
TI  - Analysis of changes in SUMO-2/3 modification during breast cancer progression and
      metastasis.
AB  - SUMOylation is an essential posttranslational modification and regulates many
      cellular processes. Dysregulation of SUMOylation plays a critical role in
      metastasis, yet how its perturbation affects this lethal process of cancer is not
      well understood. We found that SUMO-2/3 modification is greatly up-regulated in
      metastatic breast cancer cells compared with nonmetastatic control cells. To
      identify proteins differentially modified by SUMO-2/3 between metastatic and
      nonmetastatic cells, we established a method in which endogenous SUMO-2/3
      conjugates are labeled by stable isotope labeling by amino acids in cell culture
      (SILAC), immunopurified by SUMO-2/3 monoclonal antibodies and epitope-peptide
      elution, and analyzed by quantitative mass spectrometry. We identified 66
      putative SUMO-2/3-conjugated proteins, of which 15 proteins show a significant
      increase/decrease in SUMO-2/3 modification in metastatic cells. Targets with
      altered SUMOylation are involved in cell cycle, migration, inflammation,
      glycolysis, gene expression, and SUMO/ubiquitin pathways, suggesting that
      perturbations of SUMO-2/3 modification might contribute to metastasis by
      affecting these processes. Consistent with this, up-regulation of PML SUMO-2/3
      modification corresponds to an increased number of PML nuclear bodies (PML-NBs)
      in metastatic cells, whereas up-regulation of global SUMO-2/3 modification
      promotes 3D cell migration. Our findings provide a foundation for further
      investigating the effects of SUMOylation on breast cancer progression and
      metastasis. 

PMID- 25072997
TI  - Expanding horizons: increasing undergraduate exposure to tomorrow's specialties.

PMID- 25072998
TI  - Molecular dynamics simulation of the rupture mechanism in nanorod filled polymer
      nanocomposites.
AB  - Through coarse-grained molecular dynamics simulation, we aim to uncover the
      rupture mechanism of polymer-nanorod nanocomposites by characterizing the
      structural and dynamic changes during the tension process. We find that the
      strain at failure is corresponding to the coalescence of a single void into
      larger voids, namely the change of the free volume. And the minimum of the Van
      der Walls (VDWL) energy reflects the maximum mobility of polymer chains and the
      largest number of voids of polymer nanocomposites. After the failure, the stress
      gradually decreases with the strain, accompanied by the contract of the highly
      orientated polymer bundles. In particular, we observe that the nucleation of
      voids prefers to occur from where the ends of polymer chains are located. We
      systematically study the effects of the interfacial interaction, temperature, the
      length and volume fraction of nanorods, chain length, bulk cross-linking density
      and interfacial chemical bonds on the rupture behavior, such as the stress at
      failure, the tensile modulus and the rupture energy. The rupture resistance
      ability increases with the increase of the interfacial interaction, rod length,
      and bulk cross-linking density. With an increase in the interfacial interaction,
      it induces the rupture transition from mode A (no bundles) to B (bundles). The
      transition point of the stress at failure as a function of the temperature
      roughly corresponds to the glass transition temperature. At longer chain length,
      a non-zero stress plateau occurs. And excessive chemical bonds between polymers
      and nanorods are harmful to the rupture property. We find that an optimal volume
      fraction of nanorods exists for the stress-strain behavior, which can be
      rationalized by the formation of the strongest polymer-nanorod network, leading
      to the slowest mobility of nanorods. 

PMID- 25072999
TI  - Branching ratios in reactions of OH radicals with methylamine, dimethylamine, and
      ethylamine.
AB  - The branching ratios for the reaction of the OH radical with the primary and
      secondary alkylamines: methylamine (MA), dimethylamine (DMA), and ethylamine
      (EA), have been determined using the technique of pulsed laser photolysis-laser
      induced fluorescence. Titration of the carbon-centered radical, formed following
      the initial OH abstraction, with oxygen to give HO2 and an imine, followed by
      conversion of HO2 to OH by reaction with NO, resulted in biexponential OH decay
      traces on a millisecond time scale. Analysis of the biexponential curves gave the
      HO2 yield, which equaled the branching ratio for abstraction at alphaC-H
      position, r(alphaC-H). The technique was validated by reproducing known branching
      ratios for OH abstraction for methanol and ethanol. For the amines studied in
      this work (all at 298 K): r(alphaC-H,MA) = 0.76 +/- 0.08, r(alphaC-H,DMA) = 0.59
      +/- 0.07, and r(alphaC-H,EA) = 0.49 +/- 0.06 where the errors are a combination
      in quadrature of statistical errors at the 2sigma level and an estimated 10%
      systematic error. The branching ratios r(alphaC-H) for OH reacting with (CH3)2NH
      and CH3CH2NH2 are in agreement with those obtained for the OD reaction with
      (CH3)2ND (d-DMA) and CH3CH2ND2 (d-EA): r(alphaC-H,d-DMA) = 0.71 +/- 0.12 and
      r(alphaC-H,d-EA) = 0.54 +/- 0.07. A master equation analysis (using the MESMER
      package) based on potential energy surfaces from G4 theory was used to
      demonstrate that the experimental determinations are unaffected by formation of
      stabilized peroxy radicals and to estimate atmospheric pressure yields. The
      branching ratio for imine formation through the reaction of O2 with alpha carbon
      centered radicals at 1 atm of N2 are estimated as r(CH2NH2) = 0.79 +/- 0.15,
      r(CH2NHCH3) = 0.72 +/- 0.19, and r(CH3CHNH2) = 0.50 +/- 0.18. The implications of
      this work on the potential formation of nitrosamines and nitramines are briefly
      discussed.

PMID- 25073000
TI  - Uranium removal and microbial community in a H2-based membrane biofilm reactor.
AB  - We evaluated a hydrogen-based membrane biofilm reactor (MBfR) for its capacity to
      reduce and remove hexavalent uranium [U(VI)] from water. After a startup period
      that allowed slow-growing U(VI) reducers to form biofilms, the MBfR successfully
      achieved and maintained 94-95% U(VI) removal over 8 months when the U surface
      loading was 6-11 e(-) mEq/m(2)-day. The MBfR biofilm was capable of self-recovery
      after a disturbance due to oxygen exposure. Nanocrystalline UO2 aggregates and
      amorphous U precipitates were associated with vegetative cells and apparently
      mature spores that accumulated in the biofilm matrix. Despite inoculation with a
      concentrated suspension of Desulfovibrio vulgaris, this bacterium was not present
      in the U(VI)-reducing biofilm. Instead, the most abundant group in the biofilm
      community contained U(VI) reducers in the Rhodocyclaceae family when U(VI) was
      the only electron acceptor. When sulfate was present, the community dramatically
      shifted to the Clostridiaceae family, which included spores that were potentially
      involved in U(VI) reduction. 

PMID- 25073002
TI  - Interactions between collagen gene variants and risk of anterior cruciate
      ligament rupture.
AB  - The COL5A1 and COL12A1 variants are independently associated with modulating the
      risk of anterior cruciate ligament (ACL) rupture in females. The objective of
      this study was to further investigate if COL3A1 and COL6A1 variants
      independently, as well as, collagen gene-gene interactions, modulate ACL rupture
      risk. Three hundred and thirty-three South African (SA, n = 242) and Polish (PL,
      n = 91) participants with diagnosed ACL ruptures and 378 controls (235 SA and 143
      PL) were recruited. Participants were genotyped for COL3A1 rs1800255 G/A, COL5A1
      rs12722 (T/C), COL6A1 rs35796750 (T/C) and COL12A1 rs970547 (A/G). No significant
      associations were identified between COL6A1 rs35796750 and COL3A1 rs1800255
      genotypes and risk of ACL rupture in the SA cohort. The COL3A1 AA genotype was,
      however, significantly (p = 0.036) over-represented in the PL ACL group (9.9%, n
      = 9) when compared to the PL control (CON) group (2.8%, n = 4). Although there
      were genotype distribution differences between the SA and PL cohorts, the T+A
      inferred pseudo-haplotype constructed from COL5A1 and COL12A1 was significantly
      over-represented in the female ACL group when compared to the female CON group
      within the SA (T+A ACL 50.5%, T+A CON 38.1%, p = 0.022), PL (T+A ACL 56.3%, T+A
      CON 36.3%, p = 0.029) and combined (T+A ACL 51.8%, T+A CON 37.5%, p = 0.004)
      cohorts. In conclusion, the novel main finding of this study was a significant
      interaction between the COL5A1 rs12722 T/C and COL12A1 rs970547 A/G variants and
      risk of ACL injury. These results highlight the importance of investigating gene
      gene interactions in the aetiology of ACL ruptures in multiple independent
      cohorts. 

PMID- 25073003
TI  - Prostate cancer: is androgen-deprivation therapy chosen wisely?

PMID- 25073001
TI  - Blockade of the programmed death-1 pathway restores sarcoidosis CD4(+) T-cell
      proliferative capacity.
AB  - RATIONALE: Effective therapeutic interventions for chronic, idiopathic lung
      diseases remain elusive. Normalized T-cell function is an important contributor
      to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor
      receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important
      inhibitors of T-cell function. OBJECTIVES: To determine the effects of PD-1
      pathway blockade on sarcoidosis CD4(+) T-cell proliferative capacity. METHODS:
      Gene expression profiles of sarcoidosis and healthy control peripheral blood
      mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was
      used to measure ex vivo expression of PD-1 and PD-L1 on systemic and
      bronchoalveolar lavage-derived cells of subjects with sarcoidosis and control
      subjects, as well as the effects of PD-1 pathway blockade on cellular
      proliferation after T-cell receptor stimulation. Immunohistochemistry analysis
      for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy
      control lung specimens. MEASUREMENTS AND MAIN RESULTS: Microarray analysis
      demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis
      peripheral blood mononuclear cells. Immunohistochemistry analysis revealed
      increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but
      this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1(+) CD4(+)
      T cells are present systemically, compared with healthy control subjects (P <
      0.0001). Lymphocytes with reduced proliferative capacity exhibited increased
      proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with
      sarcoidosis revealed reduced PD-1(+) CD4(+) T cells with spontaneous clinical
      resolution but not with disease progression. CONCLUSIONS: Analogous to the
      effects in other chronic lung diseases, these findings demonstrate that the PD-1
      pathway is an important contributor to sarcoidosis CD4(+) T-cell proliferative
      capacity and clinical outcome. Blockade of the PD-1 pathway may be a viable
      therapeutic target to optimize clinical outcomes.

PMID- 25073004
TI  - Neuroendocrine cancer: CLARINET: new option for NETs.

PMID- 25073005
TI  - Prostate cancer: the best fit for enzalutamide in metastatic prostate cancer.
AB  - The PREVAIL trial compared enzalutamide and placebo in patients with metastatic
      castration-resistant prostate cancer who had not received prior chemotherapy,
      demonstrating an improvement in overall survival and other clinical,
      radiographic, and biochemical outcomes. Herein, the implications of these data in
      the rapidly changing landscape of metastatic prostate cancer therapy are
      discussed.

PMID- 25073006
TI  - Breast cancer: CTCs - a predictive approach for targeted cancer therapy.

PMID- 25073007
TI  - Using the systems framework for postural control to analyze the components of
      balance evaluated in standardized balance measures: a scoping review.
AB  - OBJECTIVE: To identify components of postural control included in standardized
      balance measures for adult populations. DATA SOURCES: Electronic searches of
      MEDLINE, EMBASE, and CINAHL databases using keyword combinations of postural
      balance/equilibrium, psychometrics/reproducibility of results/predictive value of
      tests/validation studies, instrument construction/instrument validation,
      geriatric assessment/disability evaluation, gray literature, and hand searches.
      STUDY SELECTION: Inclusion criteria were measures with a stated objective to
      assess balance, adult populations (18y and older), at least 1 psychometric
      evaluation, 1 standing task, a standardized protocol and evaluation criteria, and
      published in English. Two reviewers independently identified studies for
      inclusion. Sixty-six measures were included. DATA EXTRACTION: A research
      assistant extracted descriptive characteristics and 2 reviewers independently
      coded components of balance in each measure using the Systems Framework for
      Postural Control, a widely recognized model of balance. DATA SYNTHESIS:
      Components of balance evaluated in these measures were underlying motor systems
      (100% of measures), anticipatory postural control (71%), dynamic stability (67%),
      static stability (64%), sensory integration (48%), functional stability limits
      (27%), reactive postural control (23%), cognitive influences (17%), and
      verticality (8%). Thirty-four measures evaluated 3 or fewer components of
      balance, and 1 measure-the Balance Evaluation Systems Test-evaluated all
      components of balance. CONCLUSIONS: Several standardized balance measures provide
      only partial information on postural control and omit important components of
      balance related to avoiding falls. As such, the choice of measure(s) may limit
      the overall interpretation of an individual's balance ability. Continued work is
      necessary to increase the implementation of comprehensive balance assessment in
      research and practice.

PMID- 25073008
TI  - Long-term sacral magnetic stimulation for refractory stress urinary incontinence.
AB  - OBJECTIVE: To evaluate the effects of sacral magnetic stimulation (SMS) on
      functional and urodynamic improvement in patients with refractory stress urinary
      incontinence (SUI). DESIGN: A sham-controlled, double-blind, parallel study
      design with a 4.5-month follow-up. SETTING: A tertiary hospital. PARTICIPANTS:
      Women (age, 45-75y) with SUI refractory to first-line management (N=34) were
      allocated to either an experimental (n=20) group or a sham (n=14) group.
      INTERVENTIONS: The SMS protocol consisted of 5-Hz, 20-minute treatments
      administered over the bilateral third sacral roots, with the intensity set at
      approximately 70% of the maximal output, for 12 consecutive weekdays. MAIN
      OUTCOME MEASURES: Urodynamic assessments and 2 life stress questionnaires,
      namely, the Urge-Urinary Distress Inventory (U-UDI) and the Overactive Bladder
      Questionnaire (OAB-q), were administered pre- and post-SMS intervention. We
      administered the U-UDI (primary outcome measure) and the OAB-q at 3-week
      intervals during the follow-up period until 18 weeks after the final
      intervention. RESULTS: The experimental group exhibited significant improvements
      in both U-UDI and OAB-q scores postintervention (P=.011-.014) and at follow-up
      visits (P<.001-.007) compared with the sham group. In addition, significant
      increases in bladder capacity, urethral functional length, and the pressure
      transmission ratio (P=.009-.033) were noted postintervention. Multivariate
      regression analysis revealed that patients with more severe symptoms benefited
      more from SMS. A poorer baseline U-UDI score and a shorter urethral functional
      length were associated with a greater response to SMS. CONCLUSIONS: Our
      observations of a greater response to SMS in patients with more severe SUI than
      in those with mild symptoms, as well as the long-term benefits of the treatment,
      confirm the efficacy of SMS in treating SUI.

PMID- 25073009
TI  - Mechanistic insights into the allosteric modulation of opioid receptors by sodium
      ions.
AB  - The idea of sodium ions altering G-protein-coupled receptor (GPCR) ligand binding
      and signaling was first suggested for opioid receptors (ORs) in the 1970s and
      subsequently extended to other GPCRs. Recently published ultra-high-resolution
      crystal structures of GPCRs, including that of the delta-OR subtype, have started
      to shed light on the mechanism underlying sodium control in GPCR signaling by
      revealing details of the sodium binding site. Whether sodium accesses different
      receptor subtypes from the extra- or intracellular sides, following similar or
      different pathways, is still an open question. Earlier experiments in brain
      homogenates suggested a differential sodium regulation of ligand binding to the
      three major OR subtypes, in spite of their high degree of sequence similarity.
      Intrigued by this possibility, we explored the dynamic nature of sodium binding
      to delta-OR, MU-OR, and kappa-OR by means of microsecond-scale, all-atom
      molecular dynamics (MD) simulations. Rapid sodium permeation was observed
      exclusively from the extracellular milieu, and following similar binding pathways
      in all three ligand-free OR systems, notwithstanding extra densities of sodium
      observed near nonconserved residues of kappa-OR and delta-OR, but not in MU-OR.
      We speculate that these differences may be responsible for the differential
      increase in antagonist binding affinity of MU-OR by sodium resulting from
      specific ligand binding experiments in transfected cells. On the other hand,
      sodium reduced the level of binding of subtype-specific agonists to all OR
      subtypes. Additional biased and unbiased MD simulations were conducted using the
      delta-OR ultra-high-resolution crystal structure as a model system to provide a
      mechanistic explanation for this experimental observation. 

PMID- 25073010
TI  - Liver X receptor alpha (LXRalpha/NR1H3) regulates differentiation of hepatocyte
      like cells via reciprocal regulation of HNF4alpha.
AB  - BACKGROUND & AIMS: Hepatocyte-like cells, differentiated from different stem cell
      sources, are considered to have a range of possible therapeutic applications,
      including drug discovery, metabolic disease modelling, and cell transplantation.
      However, little is known about how stem cells differentiate into mature and
      functional hepatocytes. METHODS: Using transcriptomic screening, a transcription
      factor, liver X receptor alpha (NR1H3), was identified as increased during HepaRG
      cell hepatogenesis; this protein was also upregulated during embryonic stem cell
      and induced pluripotent stem cell differentiation. RESULTS: Overexpressing NR1H3
      in human HepaRG cells promoted hepatic maturation; the hepatocyte-like cells
      exhibited various functions associated with mature hepatocytes, including
      cytochrome P450 (CYP) enzyme activity, secretion of urea and albumin,
      upregulation of hepatic-specific transcripts and an increase in glycogen storage.
      Importantly, the NR1H3-derived hepatocyte-like cells were able to rescue lethal
      fulminant hepatic failure using a non-obese diabetic/severe combined
      immunodeficient mouse model. CONCLUSIONS: In this study, we found that NR1H3
      accelerates hepatic differentiation through an HNF4alpha-dependent reciprocal
      network. This contributes to hepatogenesis and is therapeutically beneficial to
      liver disease.

PMID- 25073011
TI  - Single cell and in vivo analyses elucidate the effect of xylC lactonase during
      production of D-xylonate in Saccharomyces cerevisiae.
AB  - D-xylonate is a potential platform chemical which can be produced by engineered
      Saccharomyces cerevisiae strains. In order to address production constraints in
      more detail, we analysed the role of lactone ring opening in single cells and
      populations. Both D-xylono-gamma-lactone and D-xylonate were produced when the
      Caulobacter crescentus xylB (D-xylose dehydrogenase) was expressed in S.
      cerevisiae, with or without co-expression of xylC (D-xylonolactonase), as seen by
      (1)H NMR. XylC facilitated rapid opening of the lactone and more D-xylonate was
      initially produced than in its absence. Using in vivo(1)H NMR analysis of cell
      extracts, culture media and intact cells we observed that the lactone and linear
      forms of D-xylonic acid were produced, accumulated intracellularly, and partially
      exported within 15-60min of D-xylose provision. During single-cell analysis of
      cells expressing the pH sensitive fluorescent probe pHluorin, pHluorin
      fluorescence was gradually lost from the cells during D-xylonate production, as
      expected for cells with decreasing intracellular pH. However, in the presence of
      D-xylose, only 9% of cells expressing xylB lost pHluorin fluorescence within
      4.5h, whereas 99% of cells co-expressing xylB and xylC lost fluorescence, a large
      proportion of which also lost vitality, during this interval. Loss of vitality in
      the presence of D-xylose was correlated to the extracellular pH, but fluorescence
      was lost from xylB and xylC expressing cells regardless of the extracellular
      condition. 

PMID- 25073012
TI  - Clinical outcomes of dacryocystorhinostomy with or without intraoperative use of
      mitomycin C: a systematic review and meta-analysis.
AB  - PURPOSE: To examine the possible benefit of intraoperative use of mitomycin C
      (MMC) application in dacryocystorhinostomy (DCR) and to assess its potential
      risk. METHODS: Systematic review and meta-analysis of randomized-controlled
      trials (RCTs). A comprehensive literature search was performed according to a
      protocol set in advance. The participants included 811 patients of which 820 eyes
      were sampled for 14 RCTs. Only pertinent RCTs were identified and included in
      this meta-analysis. The primary efficacy measure was "patency of irrigation" at
      follow-up end point. The subjective outcome of "symptom relief" was also
      extracted as a secondary efficacy measure. For each study, relative risk was
      extracted. Heterogeneity, publication bias, subgroup, and meta-regression
      analyses were performed. RESULTS: RevMan version 5.0 software was used for
      statistical analysis. In the primary efficacy measure, the use of MMC can
      significantly increase the rate of "patency of irrigation" [risk ratio (RR),
      1.10; 95% confidence interval (CI), 1.04-1.17; P=0.0006]; the outcome of "symptom
      relief" was also affected by the use of MMC (RR, 1.15; 95% CI, 1.05-1.26;
      P=0.003). Sensitivity analysis suggested that the result was comparatively
      reliable. CONCLUSION: Intraoperative use of MMC can bring about a positive effect
      to the outcomes of "patency of irrigation" and "symptom relief," which increases
      the success rate of DCR surgery.

PMID- 25073013
TI  - Encapsidated atom-transfer radical polymerization in Qbeta virus-like
      nanoparticles.
AB  - Virus-like particles (VLPs) are unique macromolecular structures that hold great
      promise in biomedical and biomaterial applications. The interior of the 30 nm
      diameter Qbeta VLP was functionalized by a three-step process: (1) hydrolytic
      removal of endogenously packaged RNA, (2) covalent attachment of initiator
      molecules to unnatural amino acid residues located on the interior capsid
      surface, and (3) atom-transfer radical polymerization of tertiary amine-bearing
      methacrylate monomers. The resulting polymer-containing particles were moderately
      expanded in size; however, biotin-derivatized polymer strands were only very
      weakly accessible to avidin, suggesting that most of the polymer was confined
      within the protein shell. The polymer-containing particles were also found to
      exhibit physical and chemical properties characteristic of positively charged
      nanostructures, including the ability to easily enter mammalian cells and deliver
      functional small interfering RNA. 

PMID- 25073014
TI  - Continuous droplet removal upon dropwise condensation of humid air on a
      hydrophobic micropatterned surface.
AB  - Combination of two physical phenomena, capillary pressure gradient and
      wettability gradient, allows a simple two-step fabrication process that yields a
      reliable hydrophobic self-cleaning condenser surface. The surface is fabricated
      with specific microscopic topography and further treatment with a chemically
      inert low-surface-energy material. This process does not require growth of
      nanofeatures (nanotubes) or hydrophilic-hydrophobic patterning of the surface.
      Trapezoidal geometry of the microfeatures facilitates droplet transfer from the
      Wenzel to the Cassie state and reduces droplet critical diameter. The geometry of
      the micropatterns enhances local coalescence and directional movement for
      droplets with diameter much smaller than the radial length of the micropatterns.
      The hydrophobic self-cleaning micropatterned condenser surface prevents liquid
      film formation and promotes continuous dropwise condensation cycle. Upon dropwise
      condensation, droplets follow a designed wettability gradient created with
      micropatterns from the most hydrophobic to the least hydrophobic end of the
      surface. The surface has higher condensation efficiency, due to its directional
      self-cleaning property, than a plain hydrophobic surface. We explain the self
      actuated droplet collection mechanism on the condenser surface and demonstrate
      experimentally the creation of an effective wettability gradient over a 6 mm
      radial distance. In spite of its fabrication simplicity, the fabricated surface
      demonstrates self-cleaning property, enhanced condensation performance, and
      reliability over time. Our work enables creation of a hydrophobic condenser
      surface with the directional self-cleaning property that can be used for
      collection of biological (chemical, environmental) aerosol samples or for
      condensation enhancement. 

PMID- 25073015
TI  - Lack of interaction between concurrent caffeine and mobile phone exposure on
      visual target detection: an ERP study.
AB  - BACKGROUND: Caffeine affects information processing by acting predominantly on
      cortical activation, arousal and attention. Millions consume caffeine and
      simultaneously use their mobile phone (MP) during everyday activities. However,
      it is not known whether and how MP-emitted electromagnetic fields (EMFs) can
      modulate known psychoactive effects of caffeine. Here we investigated behavioral
      and neural correlates of caffeine and simultaneous MP exposure in a third
      generation (3G) Universal Mobile Telecommunication System (UMTS) signal
      modulation scheme. METHODS: We recorded electroencephalography (EEG) and event
      related potentials (ERP) in an oddball paradigm to frequent standard (p=0.8) and
      rare target (p=0.2) stimuli in a placebo controlled, double blind, within-subject
      protocol in four experimental sessions: 1) no caffeine and no MP, 2) caffeine
      only, 3) MP only, and 4) caffeine and MP. The subjects' task was to discriminate
      between standard and target stimuli and respond to the latter by pressing a
      button while reaction time (RT) and EEG were recorded. To provide a complete
      analysis of any possible caffeine and/or MP treatment effects that may have
      occurred, we analyzed the P300 ERP wave using four different ERP measures: 1)
      peak latency, 2) peak amplitude, 3) 50% fractional area latency (FAL) and 4) area
      under the curve (AUC). RESULTS: Caffeine significantly shortened RT and decreased
      AUC of the P300 component compared to the control or the UMTS MP alone
      conditions. However, no effects were observed on RT or P300 in the UMTS MP
      exposure sessions, neither alone nor in combination with caffeine. CONCLUSION:
      Overall, the present results did not demonstrate any interactive or synergistic
      effects of caffeine and UMTS MP like EMF exposure on basic neural or cognitive
      measures. However, we found that caffeine consistently enhanced behavioral and
      ERP measures of visual target detection, showing that present results were
      obtained using a pharmacologically validated, consistent and replicable
      methodology.

PMID- 25073016
TI  - Action-FRET: probing the molecular conformation of mass-selected gas-phase
      peptides with Forster resonance energy transfer detected by acceptor-specific
      fragmentation.
AB  - The use of Forster resonance energy transfer (FRET) as a probe of the structure
      of biological molecules through fluorescence measurements in solution is well
      attested. The transposition of this technique to the gas phase is appealing since
      it opens the perspective of combining the structural accuracy of FRET with the
      specificity and selectivity of mass spectrometry (MS). Here, we report FRET
      results on gas-phase polyalanine ions obtained by measuring FRET efficiency
      through specific photofragmentation rather than fluorescence. The structural
      sensitivity of the method was tested using commercially available chromophores
      (QSY 7 and carboxyrhodamine 575) grafted on a series of small, alanine-based
      peptides of differing sizes. The photofragmentation of these systems was
      investigated through action spectroscopy, and their conformations were probed
      using ion mobility spectrometry (IMS) and Monte Carlo minimization (MCM)
      simulations. We show that specific excitation of the donor chromophore results in
      the observation of fragments that are specific to the electronic excitation of
      the acceptor chromophore. This shows that energy transfer took place between the
      two chromophores and hence that the action-FRET technique can be used as a new
      and sensitive probe of the structure of gas-phase biomolecules, which opens
      perspectives as a new tool in structural biology. 

PMID- 25073018
TI  - The Collective Impact Approach to Breastfeeding Support.

PMID- 25073019
TI  - Teaching fellowships for UK foundation doctors.
AB  - Teaching Fellowships for junior doctors in their second post-graduate (FY2) year
      should be considered by medical students and junior doctors in UK. FY2 Teaching
      Fellowships are available in many foundation schools as part of the UK Academic
      Foundation Programme. Although programme structures differ between schools, they
      are designed to allow junior trainees to take time out from clinical practice to
      develop their teaching skills and gain insights into medication education
      careers. The advantages of an FY2 teaching fellowship include valuable experience
      of teaching and formal feedback not available to other trainees; the opportunity
      to further develop your portfolio; further development of the trainee's own
      knowledge and skills; the stimulation of working with students. Potential
      drawbacks to be considered are reduced direct clinical contact; reduced salary;
      difficulty carrying out education research in the allocated time frame;
      occasional difficulties establishing the teacher-student relationship while the
      trainee is at a relatively junior level. Experience of medical education as an
      FY2 trainee provides a helpful stepping stone whether or not the trainee further
      pursues education as a career, because the teaching skills are transferable to
      any specialty, and the unique experience enhances the trainee's confidence as a
      role model for junior colleagues.

PMID- 25073017
TI  - Proton-induced reactivity of NO- from a {CoNO}8 complex.
AB  - Research on the one-electron reduced analogue of NO, namely nitroxyl (HNO/NO(-)),
      has revealed distinguishing properties regarding its utility as a therapeutic.
      However, the fleeting nature of HNO requires the design of donor molecules. Metal
      nitrosyl (MNO) complexes could serve as potential HNO donors. The synthesis,
      spectroscopic/structural characterization, and HNO donor properties of a
      {CoNO}(8) complex in a pyrrole/imine ligand frame are reported. The {CoNO}(8)
      complex [Co(LN4(PhCl))(NO)] (1) does not react with established HNO targets such
      as Fe(III) hemes or Ph3P. However, in the presence of stoichiometric H(+) 1
      behaves as an HNO donor. Complex 1 readily reacts with [Fe(TPP)Cl] or Ph3P to
      afford the {FeNO}(7) porphyrin or Ph3P?O/Ph3P?NH, respectively. In the absence of
      an HNO target, the {Co(NO)2}(10) dinitrosyl (3) is the end product. Complex 1
      also reacts with O2 to yield the corresponding Co(III)-eta(1)-ONO2 (2) nitrato
      analogue. This report is the first to suggest an HNO donor role for {CoNO}(8)
      with biotargets such as Fe(III)-porphyrins. 

PMID- 25073022
TI  - [What rhinoplasty surgeons should know about body dysmorphic disorder (BDD)].
AB  - Body dysmorphic disorder (BDD) is a psychiatric disorder characterized by an
      excessive concern with a non-existing or slight defect in physical appearance.
      BDD patients frequently show impaired judgment regarding the psychiatric origin
      of their concerns and often seek aesthetic treatment to resolve their appearance
      concerns. The central position of the nose in the face makes the nose one of the
      most common areas of concern in patients with BDD. Thus, aesthetic rhinoplasty is
      suspected to be one of the most frequently requested and performed surgical
      procedures in this population. However, there is a growing consensus that BDD
      should be considered a contraindication for aesthetic rhinoplasty, as favourable
      outcome is unlike [1-5]. In order to prevent patients from undergoing
      unsatisfying surgery and in the context of the increasing importance of medico
      legal arguments, the rhinoplasty surgeon should be familiar with BDD. This
      article provides a focused review of issues pertaining to BDD that are relevant
      to the rhinoplasty surgeon. 

PMID- 25073020
TI  - TNFalpha inhibits IGFBP-3 through activation of p38alpha and casein kinase 2 in
      human retinal endothelial cells.
AB  - We recently reported a reciprocal relationship between tumor necrosis factor
      alpha (TNFalpha) and insulin-like receptor growth factor binding protein 3 (IGFBP
      3) in whole retina of normal and IGFBP-3 knockout mice. A similar relationship
      was also observed in cultured retinal endothelial cells (REC). We found that
      TNFalpha significantly reduced IGFBP-3 levels and vice-versa, IGFBP-3 can lower
      TNFalpha and TNFalpha receptor expression. Since IGFBP-3 is protective to the
      diabetic retina and TNFalpha is causative in the development of diabetic
      retinopathy, we wanted to better understand the cellular mechanisms by which
      TNFalpha can reduce IGFBP-3 levels. For these studies, primary human retinal
      endothelial cells (REC) were used since these cells undergo TNFalpha-mediated
      apoptosis under conditions of high glucose conditions and contribute to diabetic
      retinopathy. We first cultured REC in normal or high glucose, treated with
      exogenous TNFalpha, then measured changes in potential signaling pathways, with a
      focus on P38 mitogen-activated protein kinase alpha (P38alpha) and casein kinase
      2 (CK2) as these pathways have been linked to both TNFalpha and IGFBP-3. We found
      that TNFalpha significantly increased phosphorylation of P38alpha and CK2.
      Furthermore, specific inhibitors of P38alpha or CK2 blocked TNFalpha inhibition
      of IGFBP-3 expression, demonstrating that TNFalpha reduces IGFBP-3 through
      activation of P38alpha and CK2. Since TNFalpha and IGFBP-3 are key mediators of
      retinal damage and protection respectively in diabetic retinopathy, increased
      understanding of the relationship between these two proteins will offer new
      therapeutic options for treatment. 

PMID- 25073023
TI  - [Adeno-tonsillectomy in children: preoperative coagulation screening and bleeding
      complications].
AB  - BACKGROUND: In 2006 German medical societies published recommendations: Before
      carrying out an adenoidectomy and/or a tonsillectomy in childhood a specific
      bleeding-anamnesis should be performed instead of a laboratory coagulation
      screening in order to determine a clinically relevant bleeding disorder. In the
      context of this survey it was investigated how many of the Bavarian ENT
      physicians in private practice had implemented these recommendations and what
      experiences they made with them. In addition, further data such as the number of
      performed operations and occurred bleeding complications were collected. METHOD:
      Between 2009 and 2010 a prepared questionnaire was sent to all Bavarian ENT
      physicians, who were in private practice. If even after further sent covering
      letters no reply was received they were contacted by telephone. The analysis
      period was 2008. RESULTS: In total 601 ENT physicians were contacted, whereas 495
      valid replies could be obtained (rate of valid return>80%). 325 (66%) of these
      performed surgery in 2008, but only one of 3 of these operating ENT physicians
      had completely implemented the recommendations. The rate of postoperative
      bleeding complications following tonsillectomy was 1.80%, following adenoidectomy
      0.30%. A significant difference in the postoperative bleeding rate between those,
      who had implemented the recommendations and those, who had not, could not be
      shown. But a highly significant difference favouring the surgeons, who
      quantitatively had performed more tonsillectomies could be revealed. CONCLUSION:
      The results of this retrospective survey support the recommendations given by
      German medical societies.

PMID- 25073024
TI  - ["58-year-old patient with painful, aphthous stomatitis and conjunctivitis"].

PMID- 25073025
TI  - [New risks in billing optional medical services].

PMID- 25073026
TI  - [Differential diagnosis "vertigo and dizziness"].
AB  - Vertigo and dizziness are symptoms of interdisciplinary dimension. However, the
      differentiation and classification of vertigo syndromes also require experience
      and multidisciplinary knowledge. Since the clinical syndrome is subjective, a
      detailed analysis of the complaints underlying is required. International disease
      definitions are an indispensable tool in the differential diagnosis of vertigo
      syndromes today. With simple diagnostic tools eye movement disorders and
      nystagmus can be examined and assigned to specific vestibular disorders today.
      Screening tests (e.g. head impulse test) are now an important instrument in the
      investigation of patients with vertigo syndromes in case of emergency. With
      objective diagnostic methods (caloric irrigation, video head impulse test,
      vestibular evoked myogenic potentials) the degree of functional impairment of the
      five vestibular receptors can be assessed quantitatively. Furthermore, in
      vestibulopathies, a receptor and side-specific diagnostic assessment can be
      performed even with regard to dynamic aspects.

PMID- 25073027
TI  - [The endoscopic examination, anatomical variants and special circumstances].

PMID- 25073028
TI  - Tet-mediated formation of 5-hydroxymethylcytosine in RNA.
AB  - Oxidation of 5-methylcytosine in DNA by ten-eleven translocation (Tet) family of
      enzymes has been demonstrated to play a significant role in epigenetic regulation
      in mammals. We found that Tet enzymes also possess the activity of catalyzing the
      formation of 5-hydroxymethylcytidine (5-hmrC) in RNA in vitro. In addition, the
      catalytic domains of all three Tet enzymes as well as full-length Tet3 could
      induce the formation of 5-hmrC in human cells. Moreover, 5-hmrC was present at
      appreciable levels (~1 per 5000 5-methylcytidine) in RNA of mammalian cells and
      tissues. Our results suggest the involvement of this oxidation in RNA biology. 

PMID- 25073029
TI  - Low serum mannose-binding lectin levels are associated with inflammation and
      apoptosis in early surveillance allograft biopsies.
AB  - INTRODUCTION: Mannose-binding lectin (MBL) is a protein of the innate immune
      system that participates in host defense and the tissue injury/repair process,
      enhancing the clearance of apoptotic cells by macrophages. The aim is to
      characterize the relationship between pre-transplant MBL levels, histological
      lesions and number of apoptotic cells in early surveillance renal allograft
      biopsies. PATIENTS AND METHODS: Consecutive renal transplant recipients were
      recruited and MBL levels were classified into tertiles. The first tertile was
      considered the low MBL group. Surveillance biopsies were done during the first 6
      months and were evaluated according to Banff criteria. Renal inflammatory
      infiltrates were studied by immunohistochemical techniques. Apoptosis was studied
      using morphological methods in renal tubular cells and was expressed as the
      number of apoptotic cells/mm(2). RESULTS: MBL was determined in 126 patients and
      a surveillance biopsy with sufficient tissue was obtained in 41 of them. Patients
      with low pre-transplant MBL levels showed a higher acute Banff index (3.14 +/-
      1.96 vs. 1.88 +/- 1.56, p = 0.044) and an increased proportion of biopsies with
      tubular cell apoptosis The proportion of biopsies with tubular cell apoptosis was
      higher in patients with low pre-transplant MBL levels in comparison with patients
      with high MBL levels (4.3 +/- 3.6 versus 0.2 +/- 0.9 p = 0.012) and increased
      interstitial number of inflammatory cells and significantly the macrophages/mm(2)
      (109 +/- 118 vs. 32 +/- 46; p = 0.04). CONCLUSION: Low pre-transplant serum MBL
      levels are associated with more severe inflammation and increased apoptosis in
      early surveillance renal allograft biopsies suggesting that MBL modulates renal
      inflammation after transplantation.

PMID- 25073030
TI  - System level genes or physiological adaptation?

PMID- 25073031
TI  - A method for isolating high quality RNA from mouse cortical and cancellous bone.
AB  - The high incidence of fragility fractures in cortico-cancellous bone locations,
      plus the fact that individual skeletal sites exhibit different responsiveness to
      load and disease, emphasizes the need to document separately gene expression in
      cortical and cancellous bone. A further confounding factor is marrow
      contamination since its high cellularity may effect gene expression measurements.
      We isolated RNA from cortical and cancellous bone of intact mouse tibiae, and
      also after marrow removal by flushing or centrifugation. RNA isolated from
      cancellous bone by each method was sufficient for gene expression analysis.
      Centrifugation removed contaminating cells more efficiently than flushing, as
      indexed by histology and decreased expression of Icam4, a highly expressed
      erythroid gene. In contrast, centrifuged cortical bone had 12- and 13- fold
      higher expression of the bone-related genes Col1a1 and Bglap, while levels in
      marrow-free cancellous bone were 30- and 31-fold higher when compared to bone
      where marrow was left intact. Furthermore, cortical bone had higher expression of
      Col1a1 and Bglap than cancellous bone. Thus, RNA isolated by this novel approach
      can reveal site-specific changes in gene expression in cortical and cancellous
      bone sites. 

PMID- 25073032
TI  - Association between a gain-of-function variant of PTPN22 and rejection in liver
      transplantation.
AB  - BACKGROUND: The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) encodes
      a strong T-cell regulator called lymphoid protein tyrosine phosphatase.
      Previously, PTPN22 was described as a susceptibility gene for autoimmunity
      because it contains single nucleotide polymorphisms (SNPs) associated with
      several autoimmune diseases. One SNP (rs2476601; 1858G>A) has emerged as a
      particularly potent risk factor for autoimmunity. We address the question whether
      PTPN22 polymorphisms are also associated with acute rejection after liver
      transplantation. METHODS: We investigated the influence of six PTPN22 SNPs on the
      susceptibility to acute liver allograft rejection. Consequently, we carried out a
      retrospective study genotyping 345 German liver recipients at six SNP loci, which
      include rs2488457 (-1123G>C), rs33996649 (788C>T), rs2476601 (1858G>A), rs1310182
      (-852A>G), rs1217388 (-2200G>A), rs3789604 (64434T>G). Our study enrolled 165
      recipients who did not develop rejection, 123 who showed one rejection episode,
      and 57 patients who suffered from multiple acute rejections after
      transplantation. RESULTS: The 1858A allele containing genotypes (GA+AA) and the
      1858A allele had a significantly higher frequency in the group of patients with
      multiple rejection episodes (35.1% and 18.4%) compared to rejection-free patients
      (15.8% and 7.9%; P=0.022 and 0.023). In contrast, we could not detect any
      association between rejection and the other tested SNPs. Additionally, we
      identified one haplotype contributing to risk of multiple rejections, however,
      exhibiting no stronger impact than the 1858A allele alone. CONCLUSION: We
      conclude that the 1858G>A SNP may confer susceptibility to multiple acute liver
      transplant rejections in the German population.

PMID- 25073033
TI  - Histomorphometric evaluation of ischemia-reperfusion injury and the effect of
      preservation solutions histidine-tryptophan-ketoglutarate and University of
      Wisconsin in limb transplantation.
AB  - BACKGROUND: The effect of cold ischemia (CI) in vascularized composite
      allotransplantation is unknown. We herein assess tissue-specific damage,
      acceptable CI time, and the effect of preservation solutions in a syngenic rat
      hindlimb transplant model. METHODS: Lewis rat limbs were flushed and stored for
      2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of
      Wisconsin preservation solution before transplantation. Morphologic alterations,
      inflammation, and damage of the individual tissues were analyzed on day 10 using
      histomorphology, confocal, light, and transmission-electron microscopy. RESULTS:
      Two-hour CI led to mild inflammation of tissues on day 10, whereas 10-hr and 30
      hr CI resulted in massive inflammation and tissue damage. Although muscle was
      mainly affected after prolonged CI (>=10 hr), nerve was affected in all CI
      groups. A perineural cell infiltrate, hypercellular appearance, pronounced
      vacuolization, and mucoid degeneration, appearing as Wallerian degeneration, were
      observed. Staining with propidium iodide and Syto 16 revealed a decrease in
      viable muscle cell nuclei in the anterior tibial muscle on day 10 in all groups,
      which was most pronounced in 10-hr and 30-hr CI animals. Transmission-electron
      microscopy indicated that a large number of mitochondria were degenerated in the
      10-hr and 30-hr CI groups. Histidine-tryptophan-ketoglutarate preservation
      solution slightly decreased inflammation and tissue damage compared to University
      of Wisconsin-treated and saline-treated animals, especially in skin and muscle
      when CI times did not exceed 10 hr. CONCLUSION: Severe inflammation and tissue
      damage are observed after prolonged CI in muscle and nerve. Ischemia times in
      vascularized composite allotransplantation should be kept as short as possible
      and certainly below 10 hr.

PMID- 25073034
TI  - Epidermal growth factor inhibition, a novel pathway to prevent chronic allograft
      injury.
AB  - BACKGROUND: Chronic allograft injury remains a major problem in clinical kidney
      transplantation and different growth factors participate in its development.
      Epidermal growth factor (EGF) affects cell proliferation and mitogenesis through
      its tyrosine kinase receptor. Erlotinib is an orally administered tyrosine kinase
      inhibitor used in clinical oncology to inhibit EGF signaling. We investigated its
      effect on the development of chronic allograft injury in an experimental kidney
      transplantation model. METHODS: Kidney transplantations were performed between
      Dark Agouti and Wistar Furth rats. Recipients were immunosuppressed either with
      cyclosporine A (CsA, 1.5 mg/kg/day subcutaneously) or with CsA and erlotinib (10
      mg/kg/day orally). Kidney grafts were harvested after 5 and 90 days for histology
      and immunohistochemistry. Aorta denudation model was used for the erlotinib dose
      response study to define the optimal dose for the transplantation study. RESULTS:
      Epidermal growth factor expression was increased in CsA-treated allografts which
      developed intense chronic changes on day 90. Erlotinib ameliorated neointimal
      formation in the dose response study. In addition, erlotinib decreased chronic
      rejection changes and maintained better graft function in kidney transplantation
      model. Late posttransplant EGF and EGF receptor levels were reduced with
      erlotinib. CONCLUSION: Based on these findings, EGF mediates in part the
      development of chronic allograft injury. Its inhibition with erlotinib prevents
      chronic rejection and maintains better allograft function. Therefore, EGF
      blocking by erlotinib provides a novel pathway to prevent chronic allograft
      injury.

PMID- 25073035
TI  - Improving syphilis screening in deceased organ donors.
AB  - BACKGROUND: Current U.S. policy requires screening of all deceased organ donors
      for syphilis infection. To date, information on syphilis test performance in this
      population is limited. METHODS: All donors with a positive rapid plasma reagin
      (RPR) and matched donors with negative RPR who were evaluated by one organ
      procurement organization from January 1, 2000, to September 30, 2012, were
      retrospectively tested, using retained, residual serum, with two alternate RPR
      tests and four treponemal-specific tests: A fluorescent treponemal antibody
      absorption test, a microhemagglutination test, a chemiluminescence immunoassay
      (CLIA), and a Treponema pallidum particle agglutination (TP-PA) test. RESULTS:
      Thirty-two of 3,555 (0.9%) potential deceased organ donors screened during the
      study period showed a positive RPR; 61 RPR-negative matched donor samples were
      studied as well. Thirteen (40.6%) of the RPR-positive donors were found to be
      false-positive based on confirmatory TP-PA. As compared to TP-PA, the sensitivity
      of the fluorescent treponemal antibody absorption, microhemagglutination, and
      CLIA was 87.5%, 91.7% and 100%, respectively. The CLIA and TP-PA results were
      100% concordant. Only 17 (53.1%) of the RPR-positive donors had a total of 46
      organs recovered for transplantation. CONCLUSION: Current screening of deceased
      organ donors by RPR yields a significant number of false-positive results. Use of
      alternative tests or the routine use of confirmatory tests may reduce the
      frequency of false-positive results in deceased organ donors.

PMID- 25073036
TI  - Donor-specific antibodies, C4d and their relationship with the prognosis of
      transplant glomerulopathy.
AB  - BACKGROUND: Transplant glomerulopathy (TG) is a diagnostic criterion for chronic
      active antibody-mediated rejection (CAABMR), with C4d, donor-specific antibodies
      (DSA) and other lesions of chronic tissue injury. However, TG often presents
      without C4d or DSA. Until recently, such cases were termed suspicious for CAABMR,
      and their prognosis remains unclear. METHODS: To better understand the
      contribution of TG, C4d, and DSA on outcomes, we retrospectively studied 61
      patients with late TG for the composite endpoint of death-censored graft failure
      or doubling of serum creatinine. Cases were matched to controls based on age,
      year and number of transplant, type of donor, and the availability of an
      indication biopsy during the same time after transplantation. Analyses were
      performed using proportional hazards models. RESULTS: Compared to matched
      controls, patients with TG had a more than fivefold increased risk of reaching
      the endpoint (adjusted hazard ratio (aHR), 5.3; 95% confidence interval (95% CI),
      1.5-18.4). The proportion of patients with isolated TG, TG suspicious for CAABMR
      (C4+/DSA- or C4d-/DSA+) and TG with definite CAABMR (C4d+/DSA+) were 63%, 20%,
      and 17%, respectively. Suspicious and definite CAABMR showed a similar prognosis,
      significantly worse than isolated TG (aHR, 4.5; 95% CI, 1.1-18.9 and aHR, 5.9,
      95% CI, 1.1-31.3 respectively). CONCLUSION: Transplant glomerulopathy is
      associated with poor prognosis, independent of the level of graft dysfunction and
      other chronic histologic changes. This prognosis is similar whether there is
      evidence of tissue or peripheral alloantibody reactivity. These findings are
      relevant to the development of clinically meaningful criteria for CAABMR, for its
      clinical management, and in the future selection of population for clinical
      trials.

PMID- 25073037
TI  - Utility of a monitoring strategy for human herpesviruses 6 and 7 viremia after
      liver transplantation: a randomized clinical trial.
AB  - BACKGROUND: Reactivation of human herpesvirus (HHV)-6 and HHV-7 has been linked
      to various posttransplant adverse events through immunomodulatory effects. The
      potential utility of monitoring for HHV-6 and HHV-7 viremia remains unclear.
      METHODS: In this clinical trial, 129 liver transplant recipients were randomized
      to be monitored in real-time for HHV-6 and HHV-7 viremia by polymerase chain
      reaction at regular intervals from 0 to 12 weeks after transplantation
      ("monitoring" group) or to undergo usual care ("no-monitoring" group).
      Therapeutic intervention for a positive polymerase chain reaction result included
      reduction in immunosuppression and preemptive antiviral therapy, at the
      discretion of the attending team. The primary outcome was a composite of adverse
      events indirectly attributable to viral reactivation (including opportunistic
      infection, graft rejection and severe hepatitis C virus recurrence). RESULTS: In
      the "monitoring" group, HHV-6 and HHV-7 viremia occurred in 23 of 64 patients
      (35.9%) and 21 of 64 patients (32.8%) patients, respectively. We found no cases
      of symptomatic HHV-6 and HHV-7 disease. Some therapeutic interventions were
      performed in 59.1% of viremic episodes. There were no differences in cumulative
      incidence of the primary outcome between the "monitoring" and "no-monitoring"
      groups at 1 year (58.7% vs. 52.3%; odds ratio, 0.77; 95% confidence interval,
      0.38-1.55) or at 5 years after transplantation (79.0% vs. 70.3%; odds ratio,
      0.63; 95% confidence interval, 0.28-1.42). However, we found a trend toward a
      lower incidence of graft rejection at year 1 in the "monitoring" group (30.2% vs.
      44.6%; P=0.091). CONCLUSION: In this first trial, no benefit could be
      demonstrated from routine monitoring of HHV-6 and HHV-7 viremia in graft or
      patient outcome after liver transplantation.

PMID- 25073038
TI  - Human leukocyte antigen-incompatible kidney transplantation after
      "desensitization"--hope and reality.

PMID- 25073039
TI  - An argument to abolish legal restrictions on unspecified living kidney donation.

PMID- 25073040
TI  - Diarrhea after kidney transplantation: a new look at a frequent symptom.
AB  - Diarrhea is a frequent but overlooked complication of kidney transplantation.
      Diarrhea is repeatedly neglected, often considered by patients and clinicians an
      unavoidable side effect of immunosuppressive regimens. It is, however, associated
      with a significant impairment in life quality. Severe and chronic posttransplant
      diarrhea may lead to dehydration, malabsorption, rehospitalization,
      immunosuppression, noncompliance, and a greater risk of graft loss and death.
      There is thus a need to optimize and standardize the management of posttransplant
      diarrhea with consistent diagnostic and therapeutic strategies. A recent study
      has suggested that the increased sensitivity of molecular tools might help in
      early pathogen identification and guidance of antimicrobial treatment. Most
      bacterial and protozoan infections are readily curable with appropriate
      antimicrobial agents; cryptosporidiosis and C. difficile infections may however
      be complicated by relapsing courses. In addition, identification of enteric viral
      genomes in stool has further reduced posttransplant diarrhea of unknown origin.
      Chronic norovirus-related posttransplant diarrhea, arising from the interplay of
      the virus and immunosuppressive drugs, has emerged as a new challenge in the
      field. Prospective and controlled studies are necessary to evaluate the efficacy
      and safety of innovative anti-norovirus therapeutics, as well as optimal
      immunosuppressive regimens, to enable viral clearance while preventing rejection
      and donor-specific antibody formation. This review seeks to provide a basis for
      the design of future clinical prospective studies. 

PMID- 25073041
TI  - Electronic medical records in clinical teaching.
AB  - The purpose of the project was to provide students with experiences to develop
      their technology competency and examine student perceptions about an academic
      electronic medical record (EMR) as a learning tool. Nurse educators need to
      integrate EMRs into their curricula to give students practice in the use of
      electronic documentation and retrieval of clinical information. The findings of
      this study indicated that students' use of EMRs at least 5 times resulted in the
      development of positive perceptions about their EMR experience. 

PMID- 25073042
TI  - The influence of tyre characteristics on measures of rolling performance during
      cross-country mountain biking.
AB  - This investigation sets out to assess the effect of five different models of
      mountain bike tyre on rolling performance over hard-pack mud. Independent
      characteristics included total weight, volume, tread surface area and tread
      depth. One male cyclist performed multiple (30) trials of a deceleration field
      test to assess reliability. Further tests performed on a separate occasion
      included multiple (15) trials of the deceleration test and six fixed power output
      hill climb tests for each tyre. The deceleration test proved to be reliable as a
      means of assessing rolling performance via differences in initial and final speed
      (coefficient of variation (CV) = 4.52%). Overall differences between tyre
      performance for both deceleration test (P = 0.014) and hill climb (P = 0.032)
      were found, enabling significant (P < 0.0001 and P = 0.049) models to be
      generated, allowing tyre performance prediction based on tyre characteristics.
      The ideal tyre for rolling and climbing performance on hard-pack surfaces would
      be to decrease tyre weight by way of reductions in tread surface area and tread
      depth while keeping volume high.

PMID- 25073044
TI  - Motion perception correlates with volitional but not reflexive eye movements.
AB  - Visually-driven actions and perception are traditionally ascribed to the dorsal
      and ventral visual streams of the cortical processing hierarchy. However, motion
      perception and the control of tracking eye movements both depend on sensory
      motion analysis by neurons in the dorsal stream, suggesting that the same sensory
      circuits may underlie both action and perception. Previous studies have suggested
      that multiple sensory modules may be responsible for the perception of low- and
      high-level motion, or the detection versus identification of motion direction.
      However, it remains unclear whether the sensory processing systems that
      contribute to direction perception and the control of eye movements have the same
      neuronal constraints. To address this, we examined inter-individual variability
      across 36 observers, using two tasks that simultaneously assessed the precision
      of eye movements and direction perception: in the smooth pursuit task, observers
      volitionally tracked a small moving target and reported its direction; in the
      ocular following task, observers reflexively tracked a large moving stimulus and
      reported its direction. We determined perceptual-oculomotor correlations across
      observers, defined as the correlation between each observer's mean perceptual
      precision and mean oculomotor precision. Across observers, we found that: (i)
      mean perceptual precision was correlated between the two tasks; (ii) mean
      oculomotor precision was correlated between the tasks, and (iii) oculomotor and
      perceptual precision were correlated for volitional smooth pursuit, but not
      reflexive ocular following. Collectively, these results demonstrate that sensory
      circuits with common neuronal constraints subserve motion perception and
      volitional, but not reflexive eye movements. 

PMID- 25073045
TI  - Generating bursts (and pauses) in the dopamine midbrain neurons.
AB  - Dopamine (DA) midbrain neurons project to several striatal and cortical target
      areas and are essentially involved in a puzzling variety of important brain
      functions such as action selection and motor performance, motivation and reward
      based learning, but also working memory and cognition. These neurons act via the
      release of their (main) neurotransmitter, dopamine, which binds to metabotropic
      dopamine receptors of the D1 or D2 type on target neurons. Axonal but also
      dendritic dopamine release is essentially controlled by calcium-triggered
      exocytosis of dopamine-filled synaptic vesicles primarily driven by electrical
      activity of the dopamine neuron, which generates patterns of actions potentials
      in the somato-dendritic domain and distributes them along its axonal tree. Thus,
      recording the behaviorally relevant pattern of electrical activity in DA neurons
      and identifying the underlying biophysical mechanisms that integrate afferent
      synaptic inputs and intrinsic excitability constitute a crucial element for
      defining the physiological roles of the midbrain DA system. Electrical activity
      of midbrain DA neurons in vivo is characterized by tonic background activity in a
      narrow frequency range (ca. 1-8Hz) interrupted by either transient (i.e. phasic,
      <500ms) sequences of high-frequency firing (>15Hz), so called "bursts", or
      transient pauses of electrical activity, where DA neurons generate no action
      potentials. This review focuses on the properties of these phasic activity
      changes in midbrain DA neurons. It updates recent progress on the expanding
      behavioral contexts, associated with phasic electrical activity in DA neurons
      beyond the classical (canonical) reward prediction error model. The review also
      highlights recently defined contributions of synaptic inputs for burst and pause
      generation and the roles of distinct postsynaptic ion channels in midbrain DA
      neurons. 

PMID- 25073043
TI  - Strain-dependent brain defects in mouse models of primary ciliary dyskinesia with
      mutations in Pcdp1 and Spef2.
AB  - Hydrocephalus is caused by the accumulation of cerebrospinal fluid (CSF) in the
      cerebral ventricular system which results in an enlargement of the cranium due to
      increased intraventricular pressure. The increase in pressure within the brain
      typically results in sloughing of ciliated ependymal cells, loss of cortical gray
      matter, and increased gliosis. Congenital hydrocephalus is associated with
      several syndromes including primary ciliary dyskinesia (PCD), a rare, genetically
      heterogeneous, pediatric syndrome that results from defects in motile cilia and
      flagella. We have examined the morphological and physiological defects in the
      brains of two mouse models of PCD, nm1054 and bgh, which have mutations in Pcdp1
      (also known as Cfap221) and Spef2, respectively. Histopathological and
      immunohistochemical analyses of mice with these mutations on the C57BL/6J and
      129S6/SvEvTac genetic backgrounds demonstrate strain-dependent morphological
      brain damage. Alterations in astrocytosis, microglial activation, myelination,
      and the neuronal population were identified and are generally more severe on the
      C57BL/6J background. Analysis of ependymal ciliary clearance ex vivo and CSF flow
      in vivo demonstrate a physiological defect in nm1054 and bgh mice on both genetic
      backgrounds, indicating that abnormal cilia-driven flow is not the sole
      determinant of the severity of hydrocephalus in these models. These results
      suggest that genetic modifiers play an important role in susceptibility to severe
      PCD-associated hydrocephalus. 

PMID- 25073046
TI  - Nanostructured metal sulfides for energy storage.
AB  - Advanced electrodes with a high energy density at high power are urgently needed
      for high-performance energy storage devices, including lithium-ion batteries
      (LIBs) and supercapacitors (SCs), to fulfil the requirements of future
      electrochemical power sources for applications such as in hybrid electric/plug-in
      hybrid (HEV/PHEV) vehicles. Metal sulfides with unique physical and chemical
      properties, as well as high specific capacity/capacitance, which are typically
      multiple times higher than that of the carbon/graphite-based materials, are
      currently studied as promising electrode materials. However, the implementation
      of these sulfide electrodes in practical applications is hindered by their
      inferior rate performance and cycling stability. Nanostructures offering the
      advantages of high surface-to-volume ratios, favourable transport properties, and
      high freedom for the volume change upon ion insertion/extraction and other
      reactions, present an opportunity to build next-generation LIBs and SCs. Thus,
      the development of novel concepts in material research to achieve new
      nanostructures paves the way for improved electrochemical performance. Herein, we
      summarize recent advances in nanostructured metal sulfides, such as iron
      sulfides, copper sulfides, cobalt sulfides, nickel sulfides, manganese sulfides,
      molybdenum sulfides, tin sulfides, with zero-, one-, two-, and three-dimensional
      morphologies for LIB and SC applications. In addition, the recently emerged
      concept of incorporating conductive matrices, especially graphene, with metal
      sulfide nanomaterials will also be highlighted. Finally, some remarks are made on
      the challenges and perspectives for the future development of metal sulfide-based
      LIB and SC devices. 

PMID- 25073047
TI  - Novel cyclopentadienyl tricarbonyl (99m)tc complexes containing 1
      piperonylpiperazine moiety: potential imaging probes for sigma-1 receptors.
AB  - We report the design, synthesis, and evaluation of a series of novel
      cyclopentadienyl tricarbonyl (99m)Tc complexes as potent sigma1 receptor
      radioligands. Rhenium compounds 3-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1
      yl)propylcarbonylcyclopentadienyl tricarbonyl rhenium (10a) and 4-(4-(1,3
      benzodioxol-5-ylmethyl)piperazin-1-yl)butylcarbonylcyclopentadienyl tricarbonyl
      rhenium (10b) possessed high in vitro affinity for sigma1 receptors and moderate
      to high selectivity for sigma2 receptors and the vesicular acetylcholine
      transporter. Biodistribution studies in mice demonstrated high initial brain
      uptake for corresponding (99m)Tc derivatives [(99m)Tc]23 and [(99m)Tc]24 of 2.94
      and 2.13% injected dose (ID)/g, respectively, at 2 min postinjection.
      Pretreatment of haloperidol significantly reduced the radiotracer accumulation of
      [(99m)Tc]23 or [(99m)Tc]24 in the brain. Studies of the cellular uptake of
      [(99m)Tc]23 in C6 and DU145 tumor cells demonstrated a reduction of accumulation
      by incubation with haloperidol, 1-(3,4-dimethoxyphenethyl)-4-(3
      phenylpropyl)piperazine (SA4503), or 1,3-di-o-tolyl-guanidine (DTG). Furthermore,
      blocking studies in C6 glioma-bearing mice confirmed the specific binding of
      [(99m)Tc]23 to sigma1 receptors in the tumor. 

PMID- 25073048
TI  - Creativity core to the revolution of education.

PMID- 25073049
TI  - Nurses: Leading change one day at a time.
AB  - There has been enormous progress in nursing, and that progress did not come
      without change. Nurses have two choices: to be a part of developing and leading
      the change, or to have change happen to them. 

PMID- 25073050
TI  - Critical appraisal through a new lens.
AB  - Critical appraisal is a skill that nurses require. But how can they develop it? 

PMID- 25073051
TI  - Leading the revolution in nursing practice: advancing health in the digital age.
AB  - Nursing is on the verge of a major shift in both its work and its value due to
      increasing pressure to move out of acute-care hospitals and into the community;
      and the influence of digitization in how nurses are able to provide care. 

PMID- 25073052
TI  - Commentary: Nursing must learn to adapt.
AB  - When examining the qualities required to meet the future, it is clear that if
      nursing does not learn and adapt, it will not survive; if it does not survive and
      begin to shape its environment, then it will become irrelevant. 

PMID- 25073053
TI  - Commentary: Nurses' positive impact across the continuum.
AB  - Leaders need to look far ahead, setting a course that "excites and engages"
      others in improving nurses' positive impact on health, throughout life and at the
      time of death. 

PMID- 25073054
TI  - Baccalaureate nursing education: has it delivered? A retrospective critique.
AB  - Despite political support for the baccalaureate degree as entry to practice,
      historical concerns over nursing education - the value of education versus
      service, professional versus vocational identity and theoretical versus practical
      knowledge - persist. The authors challenge the notion of a "two-tiered" nursing
      system and call for a nationwide curriculum review to help the profession adapt
      to the changing needs of the Canadian healthcare system. 

PMID- 25073055
TI  - Future directions for nursing education.
AB  - Critical reflection on the introduction to baccalaureate education as the entry
      to-practice requirement in Canada is timely. Efforts to chart future directions
      for nursing education must take into account long-standing issues from the past. 

PMID- 25073056
TI  - Boundary spanning by nurse managers: effects of managers' characteristics and
      scope of responsibility on teamwork.
AB  - Increasing role complexity has intensified the work of managers in supporting
      healthcare teams. This study examined the influence of front-line managers'
      characteristics and scope of responsibility on teamwork. Scope of responsibility
      considers the breadth of the manager's role. A descriptive, correlational design
      was used to collect cross-sectional survey and administrative data in four acute
      care hospitals. A convenience sample of 754 staff completed the Relational
      Coordination Scale as a measure of teamwork that focuses on the quality of
      communication and relationships. Nurses (73.9%), allied health professionals
      (14.7%) and unregulated staff (11.7%) worked in 54 clinical areas, clustered
      under 30 front-line managers. Data were analyzed using hierarchical linear
      modelling. Leadership practices, clinical support roles and compressed
      operational hours had positive effects on teamwork. Numbers of non-direct report
      staff and areas assigned had negative effects on teamwork. Teamwork did not vary
      by span, managerial experience, worked hours, occupational diversity or
      proportion of full-time employees. Large, acute care teaching hospitals can
      enable managers to foster teamwork by enhancing managers' leadership practices,
      redesigning the flow or reporting structure for non-direct reports, optimizing
      managerial hours relative to operational hours, allocating clinical support
      roles, reducing number of areas assigned and, potentially, introducing co-manager
      models. 

PMID- 25073057
TI  - Commuter migration: work environment factors influencing nurses' decisions
      regarding choice of employment.
AB  - Nurse migration is of global concern for every country, and study of migration
      can provide critical information for managers concerned with nurse recruitment
      and retention. This mixed-methods research examined factors influencing
      registered nurses' (RNs') decisions to work in their home country, Canada, or to
      commute daily to a nursing position in the United States. Measures included
      nurses' feelings about their work environment conditions, work status congruence
      (the goodness of fit between employer expectations and their own regarding hours
      and times worked), professional development opportunities, and their perceptions
      of organizational support and autonomy (freedom and independence) in the
      workplace. All work environment variables were significantly higher for nurses
      working in Michigan. Qualitative results supported these survey findings,
      providing additional information about nurses' satisfaction. Nurses in our sample
      were more satisfied with all the work environment factors examined, even when
      stress from commuting out of country was experienced. The environmental issues
      examined in this study should be considered by nurse managers concerned with
      recruitment and retention of nurses. 

PMID- 25073058
TI  - Graphene-based conformal devices.
AB  - Despite recent progress in bendable and stretchable thin-film transistors using
      novel designs and materials, the development of conformal devices remains limited
      by the insufficient flexibility of devices. Here, we demonstrate the fabrication
      of graphene-based conformal and stretchable devices such as transistor and
      tactile sensor on a substrate with a convoluted surface by scaling down the
      device thickness. The 70 nm thick graphene-based conformal devices displayed a
      much lower bending stiffness than reported previously. The demonstrated devices
      provided excellent conformal coverage over an uneven animal hide surface without
      the need for an adhesive. In addition, the ultrathin graphene devices formed on
      the three-dimensionally curved animal hide exhibited stable electrical
      characteristics, even under repetitive bending and twisting. The advanced
      performance and flexibility demonstrated here show promise for the development
      and adoption of wearable electronics in a wide range of future applications. 

PMID- 25073059
TI  - High-rate, ultralong cycle-life lithium/sulfur batteries enabled by nitrogen
      doped graphene.
AB  - Nitrogen-doped graphene (NG) is a promising conductive matrix material for
      fabricating high-performance Li/S batteries. Here we report a simple, low-cost,
      and scalable method to prepare an additive-free nanocomposite cathode in which
      sulfur nanoparticles are wrapped inside the NG sheets (S@NG). We show that the
      Li/S@NG can deliver high specific discharge capacities at high rates, that is, ~
      1167 mAh g(-1) at 0.2 C, ~ 1058 mAh g(-1) at 0.5 C, ~ 971 mAh g(-1) at 1 C, ~ 802
      mAh g(-1) at 2 C, and ~ 606 mAh g(-1) at 5 C. The cells also demonstrate an
      ultralong cycle life exceeding 2000 cycles and an extremely low capacity-decay
      rate (0.028% per cycle), which is among the best performance demonstrated so far
      for Li/S cells. Furthermore, the S@NG cathode can be cycled with an excellent
      Coulombic efficiency of above 97% after 2000 cycles. With a high active S content
      (60%) in the total electrode weight, the S@NG cathode could provide a specific
      energy that is competitive to the state-of-the-art Li-ion cells even after 2000
      cycles. The X-ray spectroscopic analysis and ab initio calculation results
      indicate that the excellent performance can be attributed to the well-restored C
      C lattice and the unique lithium polysulfide binding capability of the N
      functional groups in the NG sheets. The results indicate that the S@NG
      nanocomposite based Li/S cells have a great potential to replace the current Li
      ion batteries.

PMID- 25073060
TI  - Influence of mildly acidic pH conditions on the production of lentiviral and
      retroviral vectors.
AB  - Human immunodeficiency virus type 1-derived lentiviral vectors (LVs) are becoming
      major tools for gene transfer approaches. Several gene therapy clinical studies
      involving LVs are currently ongoing. Industrial production of clinical-grade LVs
      is therefore an important challenge. Some improvements in LV production protocols
      have already been possible by acting on multiple steps of the production process
      like transfection, cell culture, or media optimizations. Yet, the effects of
      physicochemical parameters such as pH remain poorly studied. Mammalian cell
      cultures are generally performed at neutral pH, which may not be the optimal
      condition to produce high quantities of LVs with optimal infectious properties.
      In this study, we showed that lentiviral transient production in HEK293T cells is
      inversely dependent on the pH value of the harvesting medium. Infectious and
      physical titers of LVs pseudotyped with GALVTR or VSV-G glycoproteins are
      enhanced by two- to threefold at pH 6 compared with neutral conditions. pH 6
      produced LVs are highly infectious on cell lines but also on relevant primary
      target cells like hCD34+ hematopoietic stem/progenitor cells. GALVTR-LV particles
      produced at pH 6 are highly stable at 37  degrees C and resistant to multiple
      freeze-thaw cycles. Higher levels of expression of intracellular pr55gag
      polyproteins are observed within HEK293T producer cells cultured at pH 6. The
      positive effect of pH 6 conditions is also observed for moloney-derived
      retroviral vectors produced from NIH-3T3 fibroblasts, arguing that the mildly
      acidic pH effect is not limited to the lentivirus genus and is reproducible in
      various producer cell lines. This observation may help us in the design of more
      effective LV production protocols for clinical applications.

PMID- 25073061
TI  - NADPH oxidase 2 mediates angiotensin II-dependent cellular arrhythmias via PKA
      and CaMKII.
AB  - RATIONALE: Angiotensin II (Ang II) signaling has been implicated in cardiac
      arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It
      was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation
      via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic
      afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which
      regulates similar targets as CaMKII has recently been shown to be redox-sensitive
      as well. OBJECTIVE: This study aims to investigate the distinct molecular
      mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the
      individual contribution of PKA vs. CaMKII. METHODS AND RESULTS: Isolated
      ventricular cardiac myocytes from rats and mice were used. Ang II exposure
      resulted in increased NOX2-dependent ROS generation assessed by expression of
      redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell
      patch clamp measurements showed that Ang II significantly increased peak Ca and
      Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and
      INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/
      )). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak
      INa and ICa were also absent. In contrast, genetic knockout of CaMKIIdelta
      (CaMKIIdelta(-/-)) did not influence the Ang II-dependent increase in peak ICa
      and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa
      and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark
      measurements) in a CaMKIIdelta-, but not PKA-dependent manner. Surprisingly, only
      the increase in diastolic SR Ca leak was absent in gp91phox(-/-)myocytes
      suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII
      but not on NOX2. Finally, we show that Ang II increased the propensity for
      cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on
      NOX2. CONCLUSION: Ang II activates PKA and CaMKII via NOX2, which results in
      disturbed Na and Ca currents (via PKA) and enhanced diastolic SR Ca leakage (via
      CaMKII). Oxidative activation of PKA and CaMKII via NOX2 may represent important
      pro-arrhythmogenic pathways in the setting of increased Ang II stimulation, which
      may be relevant for the treatment of arrhythmias in cardiac disease.

PMID- 25073062
TI  - Phosphatidylinositol 4,5-biphosphate (PIP2) modulates syntaxin-1A binding to
      sulfonylurea receptor 2A to regulate cardiac ATP-sensitive potassium (KATP)
      channels.
AB  - Cardiac sarcolemmal syntaxin (Syn)-1A interacts with sulfonylurea receptor (SUR)
      2A to inhibit ATP-sensitive potassium (KATP) channels. Phosphatidylinositol 4,5
      bisphosphate (PIP2), a ubiquitous endogenous inositol phospholipid, known to bind
      Kir6.2 subunit to open KATP channels, has recently been shown to directly bind
      Syn-1A in plasma membrane to form Syn-1A clusters. Here, we sought to determine
      whether the interaction between Syn-1A and PIP2 interferes with the ability of
      Syn-1A to bind SUR2A and inhibit KATP channel activity. We found that PIP2 dose
      dependently reduced SUR2A binding to GST-Syn-1A by in vitro pulldown assays. FRET
      studies in intact cells using TIRFM revealed that increasing endogenous PIP2
      levels led to increased Syn-1A (-EGFP) cluster formation and a severe reduction
      in availability of Syn-1A molecules to interact with SUR2A (-mCherry) molecules
      outside the Syn-1A clusters. Correspondingly, electrophysiological studies
      employing SUR2A/Kir6.2-expressing HEK cells showed that increasing endogenous or
      exogenous PIP2 diminished the inhibitory effect of Syn-1A on KATP currents. The
      physiological relevance of these findings was confirmed by ability of exogenous
      PIP2 to block exogenous Syn-1A inhibition of cardiac KATP currents in inside-out
      patches of mouse ventricular myocytes. The effect of PIP2 on physical and
      functional interactions between Syn-1A and KATP channels is specific and not
      observed with physiologic concentrations of other phospholipids. To unequivocally
      demonstrate the specificity of PIP2 interaction with Syn-1A and its impact on
      KATP channel modulation by Syn-1A, we employed a PIP2-insensitive Syn-1A-5RK/A
      mutant. The Syn-1A-5RK/A mutant retains the ability to interact with SUR2A in
      both in vitro binding and in vivo FRET assays, although as expected the
      interaction is no longer disrupted by PIP2. Interestingly, at physiological PIP2
      concentrations, Syn-1A-5RK/A inhibited KATP currents to a greater extent than Syn
      1A-WT, indicating that the inhibitory effect of Syn-1A on KATP channels is not
      due to direct competition between Syn-1A and Kir6.2 for PIP2 binding. At high
      dose PIP2, however, inhibition of KATP currents by Syn-1A-5RK/A was greatly
      reduced, likely overridden by the direct activating effect of PIP2 on KATP
      channels. Finally, depleting endogenous PIP2 with polyphosphoinositide
      phosphatase synaptojanin-1 known to disperse Syn-1A clusters, freed Syn-1A from
      Syn-1A clusters to bind SUR2A, causing optimal inhibition of KATP channels. These
      results taken together led us to conclude that PIP2 affects cardiac KATP channels
      not only by its actions on the channel directly but also by multi-modal effects
      of dynamically modulating Syn-1A mobility from Syn-1A clusters and thereby the
      availability of Syn-1A to inhibit KATP channels via interaction with SUR2A on the
      plasma membrane. 

PMID- 25073063
TI  - Discriminant validity of sense of coherence vs trait anxiety in explaining
      emotional state in an experimental task.
AB  - Prior work has indicated that sense of coherence and trait anxiety are
      overlapping constructs. This study assessed this overlap in explaining emotional
      states during a task situation. Participants were 150 students, randomly assigned
      to a control and an experimental group. The experimental task was to put a jigsaw
      puzzle together under time pressure. Sense of coherence (SOC) and trait anxiety
      were measured at baseline. The dependent variables, positive and negative
      emotions, were measured three times: at baseline, soon before the task, and after
      finishing the task. As expected, at each measurement point correlations between
      emotional state and sense of coherence did not differ significantly from the
      absolute values of the relevant correlations with trait anxiety. Also, from a
      repeated-measures perspective, for Low SOC vs High trait anxiety and also for
      High SOC vs Low trait anxiety, similar explanatory power for changes in emotional
      state was noted. The results support doubts in literature about insufficient
      discriminant validity of the Orientation to Life Questionnaire as a measure of
      the salutogenic construct.

PMID- 25073064
TI  - Analysis of the school anxiety inventory in Brazil using the Rasch rating scale
      model.
AB  - This study assessed the quality of the items of the School Anxiety Inventory
      using the Rating-Scale Rasch model. The Inventory was administered to 253 grade
      school pupils, ranging in age from 9 to 12 yr. (M = 10.2 yr., SD = 0.98); most
      were girls (52.8%). The results showed that the items and participants adequately
      fit the Rasch model. The average anxiety of these children was 0.32 logits (SD =
      1.60). The inventory items revealed good reliability (Item Reliability Index =
      0.98; Cronbach's alpha = .74), and the fit indicators for the response categories
      were adequate for 50% of the items, while the other items revealed dichotomous
      responses. No item functioned differentially for boys and girls. The psychometric
      properties of the inventory were good enough to encourage plans for further
      development.

PMID- 25073065
TI  - Violence and sexual offending behavior in people with autism spectrum disorder
      who have undergone a psychiatric forensic examination.
AB  - The increased awareness of Autism Spectrum Disorders (ASD) over the last few
      decades as well as the potential association between ASD and offending behaviors
      has spurred a need for increased research in this area. In order to explore any
      possible relationship between ASD and violent or sexual crime the present study
      examines all forensic examination reports over a 10-yr. period in Norway where
      the charged persons were diagnosed with ASD and charged with either a violent (N
      = 21) or a sexual (N = 12) offense. Differences between these two groups
      regarding previous contact with child welfare and confessions to the offense were
      found. There was also a tendency toward more severe mental health problems and
      less intellectual problems among the violent offenders than the sexual offenders.

PMID- 25073066
TI  - Ferrate(VI) oxidation of beta-lactam antibiotics: reaction kinetics,
      antibacterial activity changes, and transformation products.
AB  - Oxidation of beta-lactam antibiotics by aqueous ferrate(VI) was investigated to
      determine reaction kinetics, reaction sites, antibacterial activity changes, and
      transformation products. Apparent second-order rate constants (kapp) were
      determined in the pH range 6.0-9.5 for the reaction of ferrate(VI) with
      penicillins (amoxicillin, ampicillin, cloxacillin, and penicillin G), a
      cephalosporin (cephalexin), and several model compounds. Ferrate(VI) shows an
      appreciable reactivity toward the selected beta-lactams (kapp for pH 7 = 110-770
      M(-1) s(-1)). The pH-dependent kapp could be well explained by considering
      species-specific reactions between ferrate(VI) and the beta-lactams (with
      reactions occurring at thioether, amine, and/or phenol groups). On the basis of
      the kinetic results, the thioether is the main reaction site for cloxacillin and
      penicillin G. In addition to the thioether, the amine is a reaction site for
      ampicillin and cephalexin, and amine and phenol are reaction sites for
      amoxicillin. HPLC/MS analysis showed that the thioether of beta-lactams was
      transformed to stereoisomeric (R)- and (S)-sulfoxides and then to a sulfone.
      Quantitative microbiological assay of ferrate(VI)-treated beta-lactam solutions
      indicated that transformation products resulting from the oxidation of cephalexin
      exhibited diminished, but non-negligible residual activity (i.e., ~24% as potent
      as the parent compound). For the other beta-lactams, the transformation products
      showed much lower (<5%) antibacterial potencies compared to the parent compounds.
      Overall, ferrate(VI) oxidation appears to be effective as a means of lowering the
      antibacterial activities of beta-lactams, although alternative approaches may be
      necessary to achieve complete elimination of cephalosporin activities. 

PMID- 25073067
TI  - The mechanical response of hIAPP nanowires based on different bending direction
      simulations.
AB  - Amyloid proteins, implicated in numerous aging-related diseases, possess
      remarkable mechanical properties. Polymorphism leads to different arrangements of
      beta sheets in amyloid fibrils, which changes the characteristics of the hydrogen
      bond network that determines their mechanical properties and structural
      characteristics. We performed bending simulations using molecular dynamics
      methods under constant-velocity conditions in different bending directions. Two
      different fibril structures, parallel/homo and parallel/hetero, of hIAPP amyloids
      were considered. Though the bending configuration influences the toughness of the
      material, our results indicate that the basic material behavior is affected by
      the beta-sheet arrangement that is determined by the type of polymorphism in
      amyloid fibrils. 

PMID- 25073068
TI  - Malaria parasite genetics: doing something useful.
AB  - Genetics has informed almost every aspect of the study of malaria parasites, and
      remains a key component of much of the research that aims to reduce the burden of
      the disease they cause. We describe the history of genetic studies of malaria
      parasites and give an overview of the utility of the discipline to malariology. 

PMID- 25073069
TI  - Safety monitoring of ophthalmic biologics: a systematic review of pre- and
      postmarketing safety data.
AB  - PURPOSE: The present study evaluates the safety of the biologics approved for the
      treatment of ocular diseases. METHODS: The European medicines agency Website was
      searched to identify biologics with approved ophthalmologic therapeutic
      indications. A systematic search was performed using MEDLINE, the Cochrane
      Central Register of Controlled Trials (CENTRAL) and the International Clinical
      Trials Registry Platform up to December 2013. Pre-marketing, phase III randomized
      controlled trials (RCT), postmarketing clinical trials, observational
      longitudinal studies, and case reports involving adverse events (AE) were
      included. Methodological quality was assessed by Downs & Black checklist. All
      European spontaneous reports of AE included in the Eudravigilance up to December
      2013 were also considered. AE were classified as ocular (related and non-related
      with the injection procedure) and non-ocular (related or non-related with
      vascular endothelial growth factor inhibition). Incidences of all reported AEs
      were estimated. RESULTS: Pegaptanib, ranibizumab, and aflibercept were identified
      as ophthalmic biologics. Fourteen premarketing RCT, 7 postmarketing clinical
      trials, 31 observational studies, along with 31 case reports and 7,720
      spontaneous reports were identified and included in this study. Both in pre- and
      postmarketing settings, ocular AEs were more frequent than non-ocular AEs.
      Premarketing safety data inform the most common AEs. Postmarketing studies
      suggest an increased number of events such as retinal pigmented epithelium tears
      (0.6%-24%), thromboembolic events (0.8%-5%), and mortality (2.8%-4%).
      CONCLUSIONS: This study highlights the need to properly evaluate the risk for
      rare, serious, and long-term AEs, such as thromboembolic events, since they can
      lead to imbalances in the benefit-risk ratio of biologics in ophthalmology.

PMID- 25073070
TI  - Postoperative plasma copeptin levels independently predict delirium and cognitive
      dysfunction after coronary artery bypass graft surgery.
AB  - Copeptin can reflect individual's stress state and are correlated with poor
      outcome of critical illness. The occurrence of postoperative delirium (POD) and
      cognitive dysfunction (POCD) is associated with worse outcome after coronary
      artery bypass graft (CABG) surgery. The present study aimed to investigate the
      ability of postoperative plasma copeptin level to predict POD and POCD in
      patients undergoing CABG surgery. Postoperative plasma copeptin levels of 108
      patients were measured by an enzyme-linked immunosorbent assay. It was
      demonstrated that plasma copeptin levels were substantially higher in patients
      with POD than without POD (1.8+/-0.6 ng/mL vs. 1.1+/-0.3 ng/mL; P<0.001) and in
      patients with POCD than without POCD (1.9+/-0.6 ng/mL vs. 1.1+/-0.4 ng/mL;
      P<0.001). Plasma copeptin level and age were identified as independent predictors
      for POD [odds ratio (OR), 67.386; 95% confidence interval (CI), 12.031-377.426;
      P<0.001 and OR, 1.202; 95% CI, 1.075-1.345; P=0.001] and POCD (OR, 28.814; 95%
      CI, 7.131-116.425; P<0.001 and OR, 1.151; 95% CI, 1.030-1.285; P=0.003) using a
      multivariate analysis. For prediction of POD, the area under receiver operating
      characteristic curve (AUC) of the copeptin concentration (AUC, 0.883; 95% CI,
      0.807-0.937) was markedly higher than that of age (AUC, 0.746; 95% CI, 0.653
      0.825; P=0.020). For prediction of POCD, the AUC of the copeptin concentration
      (AUC, 0.870; 95% CI, 0.792-0.927) was markedly higher than that of age (AUC,
      0.735; 95% CI, 0.641-0.815; P=0.043). Thus, postoperative plasma copeptin level
      may be a useful, complementary tool to predict POD and POCD in patients
      undergoing CABG surgery.

PMID- 25073072
TI  - Membrane order parameters for interdigitated lipid bilayers measured via
      polarized total-internal-reflection fluorescence microscopy.
AB  - Incorporating ethanol in lipid membranes leads to changes in bilayer structure,
      including the formation of an interdigitated phase. We have used polarized total
      internal-reflection fluorescence microscopy (pTIRFM) to measure the order
      parameter for Texas Red DHPE incorporated in the ethanol-induced interdigitated
      phase (LbetaI) formed from ternary lipid mixtures comprising
      dioleoylphosphatidylcholine, cholesterol and egg sphingomyelin or
      dipalmitoylphosphatidylcholine. These lipid mixtures have 3 co-existing phases in
      the presence of ethanol: liquid-ordered, liquid-disordered and LbetaI. pTIRFM
      using Texas Red DHPE shows a reversal in fluorescence contrast between the LbetaI
      phase and the surrounding disordered phase with changes in the polarization
      angle. The contrast reversal is due to changes in the orientation of the dye, and
      provides a rapid method to identify the LbetaI phase. The measured order
      parameters for the LbetaI phase are consistent with a highly ordered membrane
      environment, similar to a gel phase. An acyl-chain labeled BODIPY-FL-PC was also
      tested for pTIRFM studies of ethanol-treated bilayers; however, this probe is
      less useful since the order parameters of the interdigitated phase are consistent
      with orientations that are close to random, either due to local membrane disorder
      or to a mixture of extended and looping conformations in which the fluorophore is
      localized in the polar headgroup region of the bilayer. In summary, we
      demonstrate that order parameter measurements via pTIRFM using Texas Red-DHPE can
      rapidly identify the interdigitated phase in supported bilayers. We anticipate
      that this technique will aid further research in the effects of alcohols and
      other additives on membranes. 

PMID- 25073071
TI  - I-J loop involvement in the pharmacological profile of CLC-K channels expressed
      in Xenopus oocytes.
AB  - CLC-K chloride channels and their subunit, barttin, are crucial for renal NaCl
      reabsorption and for inner ear endolymph production. Mutations in CLC-Kb and
      barttin cause Bartter syndrome. Here, we identified two adjacent residues, F256
      and N257, that when mutated hugely alter in Xenopus oocytes CLC-Ka's biphasic
      response to niflumic acid, a drug belonging to the fenamate class, with F256A
      being potentiated 37-fold and N257A being potently blocked with a KD~1MUM. These
      residues are localized in the same extracellular I-J loop which harbors a
      regulatory Ca(2+) binding site. This loop thus can represent an ideal and CLC-K
      specific target for extracellular ligands able to modulate channel activity.
      Furthermore, we demonstrated the involvement of the barttin subunit in the NFA
      potentiation. Indeed the F256A mutation confers onto CLC-K1 a transient
      potentiation induced by NFA which is found only when CLC-K1/F256A is co-expressed
      with barttin. Thus, in addition to the role of barttin in targeting and gating,
      the subunit participates in the pharmacological modulation of CLC-K channels and
      thus represents a further target for potential drugs. 

PMID- 25073073
TI  - Temperature dependence of backbone dynamics in human ileal bile acid-binding
      protein: implications for the mechanism of ligand binding.
AB  - Human ileal bile acid-binding protein (I-BABP), a member of the family of
      intracellular lipid binding proteins plays a key role in the cellular trafficking
      and metabolic regulation of bile salts. The protein has two internal and,
      according to a recent study, an additional superficial binding site and binds di-
      and trihydroxy bile salts with positive cooperativity and a high degree of site
      selectivity. Previously, in the apo form, we have identified an extensive network
      of conformational fluctuations on the millisecond time scale, which cease upon
      ligation. Additionally, ligand binding at room temperature was found to be
      accompanied by a slight rigidification of picosecond-nanosecond (ps-ns) backbone
      flexibility. In the current study, temperature-dependent (15)N NMR spin
      relaxation measurements were used to gain more insight into the role of dynamics
      in human I-BABP-bile salt recognition. According to our analysis, residues
      sensing a conformational exchange in the apo state can be grouped into two
      clusters with slightly different exchange rates. The entropy-enthalpy
      compensation observed for both clusters suggests a disorder-order transition
      between a ground and a sparsely populated higher energy state in the absence of
      ligands. Analysis of the faster, ps-ns motion of (15)N-(1)H bond vectors
      indicates an unusual nonlinear temperature-dependence for both ligation states.
      Intriguingly, while bile salt binding results in a more uniform response to
      temperature change throughout the protein, the temperature derivative of the
      generalized order parameter shows different responses to temperature increase for
      the two forms of the protein in the investigated temperature range. Analysis of
      both slow and fast motions in human I-BABP indicates largely different energy
      landscapes for the apo and holo states suggesting that optimization of binding
      interactions might be achieved by altering the dynamic behavior of specific
      segments in the protein. 

PMID- 25073075
TI  - Efficient hydrogen evolution by mechanically strained MoS2 nanosheets.
AB  - We demonstrated correlations between mechanically bent tensile-strain-induced two
      dimensional MoS2 nanosheets (NSs) and their electrochemical activities toward the
      hydrogen evolution reaction (HER). The tensile-strain-induced MoS2 NSs showed
      significantly steeper polarization curves and lower Tafel slopes than the strain
      free ones, which is consistent with the simple d-band model. Furthermore, the
      mechanical strain increased the electrochemical activities of all the NSs toward
      the HER except those loaded with high MoS2 mass. Mechanically bending MoS2 NSs to
      induce tensile strain enables the production of powerful, efficient
      electrocatalysis systems for evolving hydrogen. 

PMID- 25073074
TI  - Sodium dodecyl sulphate modulates the fibrillation of human serum albumin in a
      dose-dependent manner and impacts the PC12 cells retraction.
AB  - Protein aggregation is impacted by many factors including temperature, pH, and
      the presence of surfactants, electrolytes, and metal ions. The addition of sodium
      dodecyl sulphate (SDS) at different concentrations may play a significant role in
      the human serum albumin (HSA) fibrillation pathway. Here the heat induction of
      HSA fibrillation incubated with different concentrations of SDS was evaluated
      using a variety of techniques. These included ThT fluorescence, Congo red
      absorbance, circular dichroism, dynamic light scattering, and atomic force
      microscopy (AFM). To explore HSA surface properties, the surface tension of
      solutions was measured using Du Nouy Ring method tensiometry. In addition, the
      criteria of neurite outgrowth and complexity were monitored by exposing PC12
      cells to different forms of HSA amyloid intermediates. ThT fluorescence kinetic
      studies indicated that SDS at low concentrations induced more fibrillation of
      HSA, while SDS at high concentrations inhibited the fibrillation of HSA. At
      higher SDS concentrations hydrophobic forces had a significant role whereas at
      lower SDS concentrations electrostatic forces were dominant. The cell culture
      studies demonstrated the significant impact of SDS concentration on HSA
      fibrillation and subsequent neuronal cell morphology. The HSA incubated with low
      concentrations of SDS inhibited neurite outgrowth and complexity of the PC12
      cells, whereas high concentrations of SDS had lesser effect. Thus, SDS acts as a
      salt at lower concentrations, while at higher concentrations acts as a chaperon,
      with significant impact on fibrillation of HSA. 

PMID- 25073076
TI  - Do colleagues influence our lifestyle: the matter of smoking, body mass index and
      leisure-time physical activity?
AB  - OBJECTIVE: Previous research has indicated that health behaviours tend to cluster
      in social networks, but few have studied the cluster effect in workgroups. We
      examined the effect of workgroups on current state and change in three indicators
      of health behaviours (smoking, body mass index (BMI) and physical activity).
      Further, we examined whether health behaviours of the respondents at group level
      predicted lifestyle changes. METHODS: In a prospective cohort (n=4730), employees
      from 250 workgroups in the Danish eldercare sector answered questionnaires at
      baseline (2005) and follow-up (2006). Multilevel regression models were used to
      examine the effect of workgroups. RESULTS: Workgroups accounted for 6.49% of the
      variation in smoking status, 6.56% of amount smoked and 2.62% of the variation in
      current BMI. We found no significant workgroup clustering in physical activity or
      lifestyle changes. Furthermore, changes in smoking status (cessation) and weight
      gain were seen in workgroups with high percentage of smokers and high levels of
      BMI. CONCLUSION: We found modest evidence for clustering of some health
      behaviours within workgroups, which could be due to social learning or selection
      into and out of workgroups. Future health promotion programmes at worksites
      should recognize the potential clustering of lifestyle behaviours within
      workgroups.

PMID- 25073077
TI  - Self-determined motivation and physical activity in children and adolescents: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Self-determination theory is used as a framework for examining the
      relation between motivation and physical activity. The purpose of this review was
      to systematically review studies that assessed the association between self
      determined motivation and physical activity levels in children and adolescents.
      METHOD: We searched electronic databases in April 2013. Included studies assessed
      the relation between motivation (as outlined in self-determination theory) and
      physical activity in children and adolescents. RESULTS: Forty-six studies
      (n=15,984 participants) met the inclusion criteria. Meta-analysis indicated that
      overall levels of self-determined motivation had a weak to moderate, positive
      associations with physical activity (rho=.21 to .31). Autonomous forms of
      motivation (i.e., intrinsic motivation and identified regulation) had moderate,
      positive associations with physical activity (rho=.27 to .38), whereas controlled
      forms of motivation (i.e., introjection and external regulation) had weak,
      negative associations with physical activity (rho=-.03 to -.17). Amotivation had
      a weak, negative association with physical activity (rho=-.11 to -.21).
      CONCLUSIONS: Evidence provides some support for self-determination theory tenets.
      However, there was substantial heterogeneity in most associations and many
      studies had methodological shortcomings.

PMID- 25073078
TI  - Level of disability, multi-morbidity and breast cancer screening: does severity
      matter?
AB  - BACKGROUND: Women with disability may be less likely screened for breast cancer.
      Research is limited on the extent to which level of disability and multi
      morbidity influence screening. METHODS: Using a retrospective population-based
      cohort study design, we linked administrative and self-reported survey data to
      identify screening in Ontario. The cohort was identified using two waves of the
      Canadian Community Health Survey (2005 and 2007/08). Fee codes were used to
      identify mammography imaging. Rates were examined over a two-year period and
      compared across level of disability and multi-morbidity. RESULTS: Among 10,363
      women identified for study inclusion, 4660 reported some level of disability.
      Women with moderate disability had higher screening rates (71.4%) than women with
      no disability (62.0%) and women with severe disability (67.9%). We observed an
      inverse V-shaped relationship between level of disability and screening across
      all levels of multi-morbidity. In multivariate regression, women with moderate
      disability had higher odds of being screened compared to women with no disability
      (OR 1.2 [1.09-1.38]). Women with severe disability had lower odds of being
      screened compared to women with moderate disability (OR 0.72 [0.63-0.82]) and no
      disability (OR 0.88 [0.78-0.99]). Women with one chronic condition had higher
      odds of screening compared to women with no chronic conditions (OR 1.31 [1.17
      1.46]). CONCLUSIONS: Our findings suggest that severe levels of disability and
      morbidity are associated with low likelihoods of breast cancer screening.

PMID- 25073080
TI  - Calorie-labelling in catering outlets: acceptability and impacts on food sales.
AB  - OBJECTIVE: Obesity is the biggest challenge facing preventive medicine. Calorie
      labelling has been suggested as a way of changing the architecture of an
      'obesogenic' environment without limiting consumer choice. This study examined
      the effect of calorie-labelling on sales of food items at catering outlets on a
      city-centre university campus. METHODS: Sales data were collected for two
      consecutive months in 2013 on three UK university sites (two with calorie
      labelling during second month, one control) and analysed with chi-square
      'Goodness-of-Fit' tests. A questionnaire seeking consumers' views and use of the
      calorie-labelling was administered and analysed at group-level with chi-square
      tests. RESULTS: In intervention vs control sites, total sales of all labelled
      items fell significantly (-17% vs -2%, p<0.001) for the month with calorie
      labelling. Calorie-labelling was associated with substantially reduced sales of
      high-calorie labelled items, without any compensatory changes in unlabelled
      alternative items. Among 1166 student- and 646 staff-respondents, 56% reported
      using the calorie-labels, 97% of them to make lower-calorie choices. More females
      (63%) than males (40%) reported being influenced by calorie-labels when choosing
      foods (p=0.01). CONCLUSIONS: This study provides evidence, beyond that from
      single-meal exposures, for the acceptability of meal calorie-labelling and its
      potential as an effective low-cost anti-obesity measure.

PMID- 25073081
TI  - Synthetic and structural study of the coordination chemistry of a peri-backbone
      supported phosphino-phosphonium salt.
AB  - Coordination chemistry of an acenaphthene peri-backbone-supported phosphino
      phosphonium chloride (1) was investigated, revealing three distinct modes of
      reactivity. The reaction of 1 with Mo(CO)4(nor) gives the Mo(0) complex
      [(1)Mo(CO)4Cl] (2), in which the ligand 1 exhibits monodentate coordination
      through the phosphine donor and the P-P bond is retained. PtCl2(cod) reacts with
      the chloride and triflate salts of 1 to form a mononuclear complex [(1Cl)PtCl2]
      (3) and a binuclear complex [((1Cl)PtCl)2][2TfO] (4), respectively. In both of
      these complexes, the platinum center adds across the P-P bond, and subsequent
      chloride transfer to the phosphenium center results in phosphine-chlorophosphine
      bidentate coordination. [((1)PdCl)2] (5) was isolated from the reaction of 1 and
      Pd2(dba)3 (dba = dibenzylideneacetone). Oxidative addition to palladium(0)
      results in a heteroleptic phosphine bridging phosphide coordination to the Pd(II)
      center. In addition, reaction of 1 with BH3.SMe2 leads to the bis(borane) adduct
      of the corresponding mixed tertiary/secondary phosphine (6), with BH3 acting as
      both a reducing agent and a Lewis acid. The new compounds were fully
      characterized, including X-ray diffraction. The ligand properties of 1 and
      related bonding issues are discussed with help of DFT computations. 

PMID- 25073079
TI  - The health consequences of child mental health problems and parenting styles:
      unintentional injuries among European schoolchildren.
AB  - OBJECTIVE: Unintentional injury is the leading cause of death for schoolchildren.
      We assessed the association between externalizing psychopathology, parenting
      style, and unintentional injury in European children in the community. METHODS:
      Data were drawn from the School Children Mental Health in Europe project and
      included 4517 schoolchildren across seven diverse European regions. Past-year
      injuries serious enough to seek medical attention were reported by mothers. Child
      mental health problems were assessed using validated measures and reported by the
      mothers, teachers, and children. Parenting styles were based on The Parenting
      Scale and the Parent Behaviors and Attitudes Questionnaire. RESULTS: Children
      with attention-deficit/hyperactivity symptoms and oppositional defiant symptoms
      had a higher risk of injury compared to other children whether based on parent
      report (OR=1.47, 95% C.I. 1.2-1.9), teacher report (OR=1.36, 95% C.I. 1.1-1.7),
      or parent and teacher report combined (OR=1.53, 95% C.I. 1.1-2.1). Children who
      self-reported oppositional symptoms also had higher risk of injury (OR=1.6, 95%
      C.I. 1.1-2.4). Low-caring behavior of parents increased the risk of injury
      (OR=1.4, 95% C.I. 1.1-1.9). CONCLUSION: Unintentional injury is a potential
      adverse health consequence of child externalizing problems. Interventions to
      improve parent-child relationships and prevention as well as focused treatment
      for externalizing problems may reduce the burden of injury.

PMID- 25073082
TI  - Short-lived charge-transfer excitons in organic photovoltaic cells studied by
      high-field magneto-photocurrent.
AB  - The main route of charge photogeneration in efficient organic photovoltaic cells
      based on bulk hetero-junction donor-acceptor blends involves short-lived charge
      transfer excitons at the donor-acceptor interfaces. The cell efficiency is
      critically affected by the charge-transfer exciton recombination and dissociation
      processes. By measuring the magneto-photocurrent under ambient conditions at room
      temperature, we show here that magnetic field-induced spin-mixing among the
      charge-transfer exciton spin sublevels occurs in fields up to at least 8.5 Tesla.
      The resulting magneto-photocurrent increases at high fields showing non
      saturating behaviour up to the highest applied field. We attribute the observed
      high-field spin-mixing mechanism to the difference in the donor-acceptor g
      factors. The non-saturating magneto-photocurrent response at high field indicates
      that there exist charge-transfer excitons with lifetime in the sub-nanosecond
      time domain. The non-Lorentzian high-field magneto-photocurrent response
      indicates a dispersive decay mechanism that originates due to a broad
      distribution of charge-transfer exciton lifetimes. 

PMID- 25073083
TI  - In vivo live cell imaging for the quantitative monitoring of lipids by using
      Raman microspectroscopy.
AB  - A straightforward in vivo monitoring technique for biomolecules would be an
      advantageous approach for understanding their spatiotemporal dynamics in living
      cells. However, the lack of adequate probes has hampered the quantitative
      determination of the chemical composition and metabolomics of cellular lipids at
      single-cell resolution. Here, we describe a method for the rapid, direct, and
      quantitative determination of lipid molecules from living cells using single-cell
      Raman imaging. In vivo localization of lipids in the form of triacylglycerol
      (TAG) within oleaginous microalga and their molecular compositions are monitored
      with high spatial resolution in a nondestructive and label-free manner. This
      method can provide quantitative and real-time information on compositions, chain
      lengths, and degree of unsaturation of fatty acids in living cells for improving
      the cultivating parameters or for determining the harvest timing during large
      scale cultivations for microalgal lipid accumulation toward biodiesel production.
      Therefore, this technique is a potential tool for in vivo lipidomics for
      understanding the dynamics of lipid metabolisms in various organisms. 

PMID- 25073087
TI  - Granulovacuolar degeneration and unfolded protein response in mouse models of
      tauopathy and Abeta amyloidosis.
AB  - Histopathological studies on the brains of tauopathy cases including cases with
      Alzheimer's disease (AD) demonstrate that neurons with hyperphosphorylated
      protein tau display granulovacuolar degeneration (GVD), as evidenced by vacuolar
      lesions harboring a central granule, together with markers of the activated
      unfolded protein response (UPR). In order to examine whether this hallmark is
      reproduced in animal models we studied the presence of GVD and the activated UPR
      in two complementary mouse models, pR5 mice with a tau pathology and APPSLxPS1mut
      mice with an amyloid plaque pathology. Neither GVD nor a significant activation
      of the UPR was found in both APPSLxPS1mut mice and in those regions in the pR5
      brain where only neurons with an early stage of tau hyperphosphorylation were
      present. In contrast, those neurons that displayed a tau phospho-epitope
      signature that only appeared in old pR5 mice and also correlated with Gallyas
      positive tangle staining harbored granulovacuolar lesions that were labeled with
      the GVD markers casein kinases 1delta and 1epsilon. Granulovacuolar lesions in
      pR5 mice were also labeled with the UPR markers phosphorylated PKR-like
      endoplasmic reticulum kinase, phosphorylated inositol-requiring enzyme 1alpha and
      phosphorylated eukaryotic initiation factor 2alpha. However, GVD was rarely
      observed in neurons bearing mature neurofibrillary tangles as evidenced by Congo
      red staining. Our results suggest that NFT-formation activates the UPR in pR5
      mice and that it is the early stages of neurofibrillary tangle formation that are
      accompanied by GVD, in line with observations from studies on human autopsy
      cases. 

PMID- 25073088
TI  - Impairment of nasal airway under intermittent hypoxia during growth period in
      rats.
AB  - OBJECTIVE: To clarify the influences of intermittent hypoxia (IH) on the growth
      and development of the midfacial area, including the nasal cavity, in growing
      rats. DESIGN: Seven-week-old male Sprague-Dawley rats were divided into two
      groups: the experimental group (n=5), which was exposed to IH for 8h during light
      periods at a rate of 20 cycles/h (nadir, 4% O2 to peak, 21% O2 with 0% CO2), and
      the control group (n=5), which was exposed to room air. After 3 weeks, the
      maxillofacial structures in both groups were evaluated with respect to the
      height, width, length, surface area, cross-sectional area, and volume of the
      nasal cavity using soft X-ray and micro-CT. RESULTS: The experimental group
      showed a significantly smaller cross-sectional area and volume than did the
      control group. The surface area exhibited no significant differences between the
      two groups, although it tended to be smaller in the experimental group than in
      the control group. The nasal volume divided by the length of the tibia (for
      comparison with whole-body growth) was significantly smaller in the experimental
      group than in the control group. CONCLUSIONS: These data suggest that IH exposure
      suppresses growth and development of the nasal cavity and may result in nasal
      breathing disturbance.

PMID- 25073089
TI  - Synthesis and unexpected reactivity of germyliumylidene hydride [:GeH]+
      stabilized by a bis(N-heterocyclic carbene)borate ligand.
AB  - Employing the potassium salt of the monoanionic bis(NHC)borate 1 (NHC = N
      Heterocyclic Carbene) enables the synthesis and isolation of the bis(NHC)borate
      stabilized chlorogermyliumylidene precursor 2 in 61% yield. A Cl/H exchange
      reaction of 2 using potassium trisec.-butylborhydride as a hydride source leads
      to the isolation of the first germyliumylidene hydride [HGe:(+)] complex 3 in 91%
      yield. The Ge(II)-H bond in the latter compound has an unexpected reactivity as
      shown by the reaction with the potential hydride scavenger [Ph3C](+)[B(C6F5)4](
      ), furnishing the corresponding HGe: -> CPh3 cation in the ion pair 4 as initial
      product. Compound 4 liberates HCPh3 in the presence of 3 to give the unusual
      dinuclear HGe: -> Ge: cation in 5. The latter represents the first three
      coordinate dicationic Ge(II) species stabilized by an anionic bis(NHC) chelate
      ligand and a Ge(II) donor. All novel compounds were fully characterized,
      including X-ray diffraction analyses. 

PMID- 25073090
TI  - Distinct roles of soluble and transmembrane adenylyl cyclases in the regulation
      of flagellar motility in Ciona sperm.
AB  - Adenylyl cyclase (AC) is a key enzyme that synthesizes cyclic AMP (cAMP) at the
      onset of the signaling pathway to activate sperm motility. Here, we showed that
      both transmembrane AC (tmAC) and soluble AC (sAC) are distinctly involved in the
      regulation of sperm motility in the ascidian Ciona intestinalis. A tmAC inhibitor
      blocked both cAMP synthesis and the activation of sperm motility induced by the
      egg factor sperm activating and attracting factor (SAAF), as well as those
      induced by theophylline, an inhibitor of phoshodiesterase. It also significantly
      inhibited cAMP-dependent phosphorylation of a set of proteins at motility
      activation. On the other hand, a sAC inhibitor does not affect on SAAF-induced
      transient increase of cAMP, motility activation or protein phosphorylation, but
      it reduced swimming velocity to half in theophylline-induced sperm. A sAC
      inhibitor KH-7 induced circular swimming trajectory with smaller diameter and
      significantly suppressed chemotaxis of sperm to SAAF. These results suggest that
      tmAC is involved in the basic mechanism for motility activation through cAMP
      dependent protein phosphorylation, whereas sAC plays distinct roles in increase
      of flagellar beat frequency and in the Ca2+-dependent chemotactic movement of
      sperm. 

PMID- 25073091
TI  - Chikusetsu saponin V attenuates MPP+-induced neurotoxicity in SH-SY5Y cells via
      regulation of Sirt1/Mn-SOD and GRP78/caspase-12 pathways.
AB  - Studies have shown that saponins from Panax japonicus (SPJ) possess
      neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most
      abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4
      phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we
      aimed to investigate the neuroprotective effects of CsV on MPP+-induced
      cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible
      mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity,
      inhibits ROS accumulation, and increases mitochondrial membrane potential dose
      dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA
      significantly decreased in MPP+-treated group but were restored with CsV
      treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12
      mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV
      inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a
      dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these
      results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved
      in the CsV-mediated neuroprotective effects. 

PMID- 25073092
TI  - Effects of antidepressants on IP-10 production in LPS-activated THP-1 human
      monocytes.
AB  - Major depressive disorder and cardiovascular disease are common serious illnesses
      worldwide. Selective serotonin reuptake inhibitors and norepinephrine-dopamine
      reuptake inhibitors may reduce the mortality of cardiovascular disease patients
      with comorbid depression. Interferon-gamma-inducible protein 10 (IP-10), a type 1
      T helper cell (Th1)-related chemokine, contributes to manifestations of
      atherosclerosis during cardiovascular inflammations; however, the
      pathophysiological mechanisms linking cardiovascular disease and effective
      antidepressants have remained elusive. We investigated the in vitro effects of
      six different classes of antidepressants on the IP-10 chemokine expression in
      lipopolysaccharide (LPS)-stimulated monocytes, and their detailed intracellular
      mechanisms. The human monocytes were pretreated with antidepressants (10-8-10-5
      M) before LPS-stimulation. IP-10 was measured by enzyme-linked immunosorbent
      assay (ELISA) and then intracellular signaling was investigated using Western
      blotting and chromatin immunoprecipitation. Fluoxetine and bupropion suppressed
      LPS-induced IP-10 expression in monocytes, and they had no cytotoxic effects.
      Furthermore, fluoxetine inhibited LPS-induced IP-10 expression via the mitogen
      activated protein kinase (MAPK)-p38 pathway. Fluoxetine and bupropion could not
      only treat depression but also reduce Th1-related chemokine IP-10 production in
      human monocytes. Our results may indicate a possible mechanism related to how
      particular antidepressants reduce the risk of cardiovascular disease.

PMID- 25073093
TI  - Disruption of phosphoinositide-specific phospholipases Cgamma1 contributes to
      extracellular matrix synthesis of human osteoarthritis chondrocytes.
AB  - Osteoarthritis (OA) is a degenerative joint disease characterized by articular
      cartilage degradation including extracellular matrix (ECM) degradation and cell
      loss. It is known that phosphoinositide-specific phospholipase gamma1 (PLCgamma1)
      can trigger several signaling pathways to regulate cell metabolism. However,
      whether this kinase is expressive and active in human OA chondrocytes and its
      role in the pathological progression of OA have not been investigated. The
      current study was designed to investigate the PLCgamma1 expression in human OA
      cartilage, and whether PLCgamma1 was involved in the ECM synthesis had been
      further explored using cultured human OA chondrocytes. Our results indicated that
      PLCgamma1 was highly expressed in human OA chondrocytes. In our further study
      using the cultured human OA chondrocytes, the results demonstrated that the
      disruption of PLCgamma1 by its inhibitor, U73122, and siRNA contributed to the
      ECM synthesis of human OA chondrocytes through regulating the expression of ECM
      related signaling molecules, including MMP-13, Col II, TIMP1, Sox-9, and AGG.
      Furthermore, PLCgamma1/IP3/Ca2+/CaMK II signaling axis regulated the ECM
      synthesis of human chondrocytes through triggering mTOR/P70S6K/S6 pathway. In
      summary, our results suggested that PLC-gamma1 activities played an important
      role in the ECM synthesis of human OA chondrocytes, and may serve as a
      therapeutic target for treating OA.

PMID- 25073094
TI  - The extracellular entrance provides selectivity to serotonin 5-HT7 receptor
      antagonists with antidepressant-like behavior in vivo.
AB  - The finding that ergotamine binds serotonin receptors in a less conserved
      extended binding pocket close to the extracellular entrance, in addition to the
      orthosteric site, allowed us to obtain 5-HT7R antagonist 6 endowed with high
      affinity (Ki=0.7 nM) and significant 5-HT1AR selectivity (ratio>1428). Compound 6
      exhibits in vivo antidepressant-like effect (1 mg/kg, ip) mediated by the 5-HT7R,
      which reveals its interest as a putative research tool or pharmaceutical in
      depression disorders.

PMID- 25073095
TI  - Selective deposition of redox co-catalyst(s) to improve the photocatalytic
      activity of single-domain ferroelectric PbTiO3 nanoplates.
AB  - With the assistance of a ferroelectric field in PbTiO3 nanoplates, noble metals
      and metal oxides can be selectively deposited on the positively and negatively
      charged {001} facets of the nanoplates. Compared to PbTiO3 with randomly
      deposited reducing co-catalyst Pt particles, photocatalytic H2 evolution on
      PbTiO3 with Pt particles selectively deposited on the positively charged {001}
      facet is an order of magnitude better. 

PMID- 25073096
TI  - Evaluation of genipin on human cytochrome P450 isoenzymes and P-glycoprotein in
      vitro.
AB  - Genipin is obtained from the fruit of Gardenia jasminoides Ellis and acts as an
      herbal medicine or functional food in East Asia. In addition to produce natural
      colorant, it possesses widely antiinflammatory, antithrombotic, antidepressive
      and anticarcinogenic activities. However, little research focuses on the
      potential of genipin for drug-drug interactions. In this study, effects of
      genipin on mRNA and protein expression of cytochrome P450 (CYP) 2C19, CYP2D6 and
      CYP3A4 were detected by real-time reverse-transcription polymerase chain reaction
      (real-time RT-PCR) and Western blot, respectively, in human hepatoma HepG2 cells.
      Enzyme activities of which were detected by luminogenic CYP assay in vitro.
      Moreover, effect of genipin on P-glycoprotein expression was analyzed by Western
      blot. Results showed that genipin possessed a significant induction on CYP2D6 and
      a remarkable inhibition on CYP2C19 and CYP3A4 not only from the expression of
      mRNA and protein (P<0.05 or P<0.01), but the level of enzyme activity. Moreover,
      a concentration-dependent induction of genipin on P-glycoprotein expression was
      observed. In conclusion, caution should be exercised with respect to the
      induction or inhibition of genipin on CYP isoenzymes and the strong induction on
      P-glycoprotein. 

PMID- 25073097
TI  - Triterpenoids and alpha-glucosidase inhibitory constituents from Salacia
      hainanensis.
AB  - Thirteen triterpenoids (1-13), including two new lupane triterpenoids, salacinins
      A and B (1 and 2), as well as one new friedelane triterpenoid, salacinin C (3),
      were isolated from the roots and stems of Salacia hainanensis. The structures of
      new compounds were elucidated by extensive spectroscopic analysis including 1D
      and 2D NMR, and MS experiments. Compound 1 possesses rare 2,3-seco-lupane
      skeleton. Compounds 4, 6 and 7 showed inhibitory effects on alpha-glucosidase in
      vitro.

PMID- 25073098
TI  - Angle-specific hamstring-to-quadriceps ratio: a comparison of football players
      and recreationally active males.
AB  - It is currently unclear how football participation affects knee-joint muscle
      balance, which is widely considered a risk factor for hamstrings injury. This
      study compared the angle-specific functional hamstring-to-quadriceps (H:Q) ratio
      (hamstrings eccentric torque as a ratio of quadriceps concentric torque at the
      same knee-joint angle) of football players with recreationally active controls.
      Ten male footballers and 14 controls performed maximal voluntary isometric and
      isovelocity concentric and eccentric contractions (60, 240 and 400 degrees  s(
      1)) of the knee extensors and flexors. Gaussian fitting to the raw torque values
      was used to interpolate torque values for knee-joint angles of 100-160 degrees 
      (60 degrees  s(-1)), 105-160 degrees  (240 degrees  s(-1)) and 115-145 degrees 
      (400 degrees  s(-1)). The angle-specific functional H:Q ratio was calculated from
      the knee flexors eccentric and knee extensors concentric torque at the same
      velocity and angle. No differences were found for the angle-specific functional
      H:Q ratio between groups, at any velocity. Quadriceps and hamstrings strength
      relative to body mass of footballers and controls was similar for all velocities,
      except concentric knee flexor strength at 400 degrees  s(-1) (footballers +40%; P
      < 0.01). In previously uninjured football players, there was no intrinsic muscle
      imbalance and therefore the high rate of hamstring injuries seen in this sport
      may be due to other risk factors and/or simply regular exposure to a high-risk
      activity.

PMID- 25073099
TI  - Effect of water treatment additives on lime softening residual trace chemical
      composition--implications for disposal and reuse.
AB  - Drinking water treatment residues (WTR) offer potential benefits when recycled
      through land application. The current guidance in Florida, US allows for
      unrestricted land application of lime softening WTR; alum and ferric WTR require
      additional evaluation of total and leachable concentrations of select trace
      metals prior to land application. In some cases a mixed WTR is produced when lime
      softening is accompanied by the addition of a coagulant or other treatment
      chemical; applicability of the current guidance is unclear. The objective of this
      research was to characterize the total and leachable chemical content of WTR from
      Florida facilities that utilize multiple treatment chemicals. Lime and mixed lime
      WTR samples were collected from 18 water treatment facilities in Florida. Total
      and leachable concentrations of the WTR were measured. To assess the potential
      for disposal of mixed WTR as clean fill below the water table, leaching tests
      were conducted at multiple liquid to solid ratios and under reducing conditions.
      The results were compared to risk-based soil and groundwater contamination
      thresholds. Total metal concentrations of WTR were found to be below Florida soil
      contaminant thresholds with Fe found in the highest abundance at a concentration
      of 3600 mg/kg-dry. Aluminum was the only element that exceeded the Florida
      groundwater contaminant thresholds using SPLP (95% UCL = 0.23 mg/L; risk
      threshold = 0.2 mg/L). Tests under reducing conditions showed elevated
      concentrations of Fe and Mn, ranging from 1 to 3 orders of magnitude higher than
      SPLP leachates. Mixed lime WTR concentrations (total and leachable) were lower
      than the ferric and alum WTR concentrations, supporting that mixed WTR are
      appropriately represented as lime WTR. Testing of WTR under reducing conditions
      demonstrated the potential for release of certain trace metals (Fe, Al, Mn) above
      applicable regulatory thresholds; additional evaluation is needed to assess
      management options where reducing conditions may develop. 

PMID- 25073100
TI  - A fibrin-specific monoclonal antibody from a designed phage display library
      inhibits clot formation and localizes to tumors in vivo.
AB  - Fibrin formation from fibrinogen is a rare process in the healthy organism but is
      a pathological feature of thrombotic events, cancer and a wide range of
      inflammatory conditions. We have designed and constructed an antibody phage
      display library (containing 13 billion clones) for the selective recognition of
      the N-terminal peptide of fibrin alpha chain. The key structural feature for
      selective fibrin binding was a K94E mutation in the VH domain. From this library,
      an antibody was isolated (termed AP2), which recognizes the five N-terminal amino
      acids of fibrin with high affinity (Kd=44nM), but does not bind to fibrinogen.
      The AP2 antibody could be expressed in various formats (scFv, small immune
      protein and IgG) and inhibited fibrin clot formation in a concentration-dependent
      manner. Moreover, the AP2 antibody stained the fibrin-rich provisional stroma in
      solid tumors but did not exhibit any detectable staining toward normal tissues.
      Using a radioiodinated antibody preparation and quantitative biodistribution
      studies in tumor-bearing mice, AP2 was shown to selectively localize to fibrin
      rich F9 murine teratocarcinomas, but not to SKRC-52 human kidney cancer
      xenografts. Collectively, the experiments indicate that the AP2 antibody
      recognizes fibrin in vitro and in vivo. The antibody may facilitate the
      development of fibrin-specific therapeutic agents. 

PMID- 25073101
TI  - Regulation of HIV-1 latency by chromatin structure and nuclear architecture.
AB  - Current antiretroviral therapies fail to cure HIV-1 (human immunodeficiency virus
      type 1) infection because HIV-1 persists as a transcriptionally inactive provirus
      in resting memory CD4(+) T cells. Multiple molecular events are known to regulate
      HIV-1 gene expression, yet the mechanisms governing the establishment and
      maintenance of latency remain incompletely understood. Here we summarize
      different molecular aspects of viral latency, from its establishment in resting
      CD4(+) T cells to the mechanisms involved in the reactivation of latent viral
      reservoirs. We focus on the relevance of chromatin structure and nuclear
      architecture in determining the transcriptional fate of integrated HIV-1 genomes,
      in light of recent findings indicating that proximity to specific subnuclear
      neighborhoods regulates HIV-1 gene expression. 

PMID- 25073102
TI  - Control of RecBCD enzyme activity by DNA binding- and Chi hotspot-dependent
      conformational changes.
AB  - Faithful repair of DNA double-strand breaks by homologous recombination is
      crucial to maintain functional genomes. The major Escherichia coli pathway of DNA
      break repair requires RecBCD enzyme, a complex protein machine with multiple
      activities. Upon encountering a Chi recombination hotspot (5' GCTGGTGG 3') during
      DNA unwinding, RecBCD's unwinding, nuclease, and RecA-loading activities change
      dramatically, but the physical basis for these changes is unknown. Here, we
      identify, during RecBCD's DNA unwinding, two Chi-stimulated conformational
      changes involving RecC. One produced a marked, long-lasting, Chi-dependent
      increase in protease sensitivity of a small patch, near the Chi recognition
      domain, on the solvent-exposed RecC surface. The other change was identified by
      crosslinking of an artificial amino acid inserted in this RecC patch to RecB.
      Small-angle X-ray scattering analysis confirmed a major conformational change
      upon binding of DNA to the enzyme and is consistent with these two changes. We
      propose that, upon DNA binding, the RecB nuclease domain swings from one side of
      RecC to the other; when RecBCD encounters Chi, the nuclease domain returns to its
      initial position determined by crystallography, where it nicks DNA exiting from
      RecC and loads RecA onto the newly generated 3'-ended single-stranded DNA during
      continued unwinding; a crevice between RecB and RecC increasingly narrows during
      these steps. This model provides a physical basis for the intramolecular "signal
      transduction" from Chi to RecC to RecD to RecB inferred previously from genetic
      and enzymatic analyses, and it accounts for the enzymatic changes that accompany
      Chi's stimulation of recombination. 

PMID- 25073103
TI  - Activated FoxM1 attenuates streptozotocin-mediated beta-cell death.
AB  - The forkhead box transcription factor FoxM1, a positive regulator of the cell
      cycle, is required for beta-cell mass expansion postnatally, during pregnancy,
      and after partial pancreatectomy. Up-regulation of full-length FoxM1, however, is
      unable to stimulate increases in beta-cell mass in unstressed mice or after
      partial pancreatectomy, probably due to the lack of posttranslational activation.
      We hypothesized that expression of an activated form of FoxM1 could aid in
      recovery after beta-cell injury. We therefore derived transgenic mice that
      inducibly express an activated version of FoxM1 in beta-cells (RIP-rtTA;TetO
      hemagglutinin (HA)-Foxm1(Delta)(NRD) mice). This N-terminally truncated form of
      FoxM1 bypasses 2 posttranslational controls: exposure of the forkhead DNA binding
      domain and targeted proteasomal degradation. Transgenic mice were subjected to
      streptozotocin (STZ)-induced beta-cell ablation to test whether activated FoxM1
      can promote beta-cell regeneration. Mice expressing HA-FoxM1(DeltaNRD) displayed
      decreased ad libitum-fed blood glucose and increased beta-cell mass. beta-Cell
      proliferation was actually decreased in RIP-rtTA:TetO-HA-Foxm1(NRD) mice compared
      with that in RIP-rtTA mice 7 days after STZ treatment. Unexpectedly, beta-cell
      death was decreased 2 days after STZ treatment. RNA sequencing analysis indicated
      that activated FoxM1 alters the expression of extracellular matrix and immune
      cell gene profiles, which may protect against STZ-mediated death. These studies
      highlight a previously underappreciated role for FoxM1 in promoting beta-cell
      survival. 

PMID- 25073104
TI  - Genome-wide analysis of histone modifications in human endometrial stromal cells.
AB  - Dramatic changes of gene expressions occur in human endometrial stromal cells
      (ESCs) during decidualization. The changes in gene expression are associated with
      changes of chromatin structure, which are regulated by histone modifications.
      Here we investigated genome-wide changes in histone modifications associated with
      decidualization in human ESCs using chromatin immunoprecipitation combined with
      next-generation sequencing. ESCs were incubated with estradiol and
      medroxyprogesterone acetate for 14 days to induce decidualization. The chromatin
      immunoprecipitation-sequence data showed that induction of decidualization
      increased H3K27ac and H3K4me3 signals in many genomic regions but decreased in
      only a few regions. Most of the H3K27ac-increased regions (80%) and half of the
      H3K4me3-increased regions were located in the distal promoter regions (more than
      3 kb upstream or downstream of the transcription start site). RNA sequence showed
      that induction of decidualization up-regulated 881 genes, 223 of which had
      H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter
      regions. Induction of decidualization increased the mRNA levels of these genes
      more than it increased the mRNA levels of genes without H3K27ac- or H3K4me3
      increased regions. Pathway analysis revealed that up-regulated genes with the
      H3K27ac- or H3K4me3-increased regions were associated with the insulin signaling,
      which may be involved in glucose uptake that is necessary for ESCs to undergo
      decidualization. These results show that histone modification statuses on a
      genome-wide basis change in human ESCs during decidualization. The main changes
      of histone modifications are increases of H3K27ac and H3K4me3 in both the
      proximal and distal promoter regions, which are involved in the up-regulation of
      gene expression that occurs during decidualization. 

PMID- 25073106
TI  - Pharmacokinetic study of HS061, a new human insulin, in non-diabetic rat using
      ultra performance liquid chromatography-tandem mass spectrometry.
AB  - HS061, a new structure analogue of human insulin, was investigated for the
      treatment of diabetes. In this study, we developed a simple and accurate UPLC
      MS/MS method for the pharmacokinetic studies of HS061 in non-diabetic rats
      followed by a full method validation. Following a simple protein precipitation
      with acetonitrile, the analyte and internal standard (Levemir, IS) were separated
      on a Waters XBridgeTM BEH300 C4 column (100 mm * 4.6 mm i.d., 3.5 MUm) with a
      gradient elution using acetonitrile and 0.2% aqueous formic acid. The method was
      operated under pseudo-multiple reaction monitoring (pseudo-MRM) in the positive
      electrospray ionization mode. The monitored transitions were set at m/z 1563.4
      >1563.4 for HS061 by pseudo-MRM and m/z 1184.7->454.5 for IS by MRM. Linear
      calibration curves were obtained over the concentration ranges of 10-1000 ng/mL
      and no interfering peaks were detected at the retention time of HS061 and IS in
      blank rat plasma. The mean extraction recoveries of HS061 at three concentrations
      of 20, 100, 800 ng/mL were greater than 95.17%. Stability was assessed under
      different conditions and no significant degradations were found. The validated
      method was then successfully applied in measuring HS061 following subcutaneous
      (0.5, 1.0, 3.0 U/kg) and intravenous (1.0 U/kg) injection in rat plasma to
      support the pre-clinical pharmacokinetic study. Maximum plasma concentration
      (Cmax) and area under the curve (AUC) for the subcutaneous doses of HS061 was
      approximately dose proportional while other pharmacokinetic parameters showed no
      significant differences among the three doses (p>0.05). The absolute
      bioavailability of HS061 after subcutaneous administration at 1.0 U/kg was
      estimated to be 70.40%.

PMID- 25073105
TI  - Regulation of human growth hormone receptor expression by microRNAs.
AB  - Human GH binds to its receptor (GHR) on target cells and activates multiple
      intracellular pathways, leading to changes in gene expression, differentiation,
      and metabolism. GHR deficiency is associated with growth and metabolic disorders
      whereas increased GHR expression has been reported in certain cancers, suggesting
      that the GHR gene requires tight controls. Several regulatory mechanisms have
      been found within its 5'-untranslated region (UTR) promoter and coding regions.
      However, the 3'-UTR has not been previously examined. MicroRNAs (miRNAs) are
      small (19-22 nucleotides) noncoding RNAs that downregulate gene expression mainly
      through targeting the 3'-UTR of mRNAs and enhancing their degradation or
      inhibiting translation. In the present study, we investigated whether miRNAs
      regulate GHR expression. To define putative miRNA binding sites in the GHR 3'
      UTR, we used multiple in silico prediction tools, analyzed conservation across
      species and the presence of parallel sites in GH/IGF axis-related genes, and
      searched for reports linking miRNAs to GHR-related physiological or
      pathophysiological activities. To test prioritized sites, we cotransfected a wild
      type GHR 3'-UTR luciferase reporter vector as well as miRNA binding site mutants
      into HEK293 cells with miRNA mimics. Furthermore, we tested whether the miRNAs
      altered endogenous GHR mRNA and protein levels in HEK293 cells and in 2 cancer
      cell lines (MCF7 and LNCaP). Our experiments have identified miRNA (miR)-129-5p,
      miR-142-3p, miR-202, and miR-16 as potent inhibitors of human GHR expression in
      normal (HEK293) and cancer (MCF7 and LNCaP) cells. This study paves the way for
      the development of miRNA inhibitors as therapeutic agents in GH/GHR-related
      pathophysiologies, including cancer. 

PMID- 25073108
TI  - Lowest adverse effects concentrations (LOAECs) for formaldehyde exposure.
AB  - In 2012 the Committee for Risk Assessment (RAC) of the European Chemicals Agency
      concluded that 2ppm formaldehyde represent a Lowest Observed Adverse Effect
      Concentration (LOAEC) for polypoid adenomas, histopathological lesions and cell
      proliferation. An analysis of all data shows that a LOAEC of 2ppm it is not
      justified for cell proliferation and polypoid adenomas. Higher values are also
      supported by a new statistical analysis. For histopathological lesions a NOAEC of
      1ppm may be defined but the lesions at 2ppm cannot be regarded as pre-stages for
      tumour development. One major uncertainty exists: the description of polypoid
      adenomas and the lesions at 2ppm often is insufficient and diagnostic
      uncertainties can only be resolved by a re-evaluation according to modern
      histomorphological standards. Although the discrepancy between our assessment and
      that of RAC may seem rather small we feel the LOAECs proposed by RAC must be
      challenged taking into consideration the broad data base for formaldehyde and the
      potential impact of any published RAC opinion on the present discussions about
      appropriate occupational and indoor exposure limits. 

PMID- 25073107
TI  - pH responsive poly amino-acid hydrogels formed via silk sericin templating.
AB  - Poly(amino acid) hydrogels have attracted a great deal of attention as
      biodegradable biomaterials that can limit products of synthetic polymer
      degradation. Here we report on a stimuli-responsive, porous, composite
      biomaterial based on the protein templating of the poly(amino acid) hydrogel from
      poly(aspartic acid) with the silk protein sericin. This low-cost, biocompatible
      and biodegradable hydrogel demonstrates a greatly increased porosity and
      improvement in volumetric swelling over networks formed from pure poly(aspartic
      acid). The swelling capacity measured over a range of pH values surrounding
      physiological pH 7.0 demonstrates a linear profile, in which hydrogel volume and
      mass increase to a maximum, with an increase as a function of higher sericin
      content. In comparison to pure poly(aspartic acid), this demonstrates a nearly 3
      fold increase in retention volume at basic pH. The increase in swelling is also
      demonstrated by the increase in porosity and internal micro-architecture of the
      hydrogel networks. The biomaterial is then shown to perform well as a scaffold
      for cells with high mechanical strength and integrity. This protein- and homo
      poly(amino acid)-based super-swelling hydrogel has applications in drug delivery
      and tissue engineering as an economical and environmentally friendly biomaterial,
      in addition to ensuring the species incorporated maintain their biocompatibility
      during processing. 

PMID- 25073109
TI  - Toxicology and the chemical foundation of plants of Erycibe.
AB  - Erycibe is a relatively small genus in the family Convolvulaceae with over 10
      identified species. Some Erycibe plant species are purportedly toxic at high
      doses. However, few toxicology studies have been conducted on those species. In
      this study, the toxicity of 40% ethanolic extracts of Erycibeobtusifolia,
      Erycibeschmidtii, and Erycibeellipptimba was evaluated. E. ellipptimba has been
      reported to be more toxic due to containing larger amounts of Baogongteng C, an
      alkaloid with known toxicity. Thus, E. ellipptimba was chosen for further
      toxicology study here. An HPLC-MS method was developed to identify the main
      components and determine the percentages of Baogongteng C in total alkaloid of E.
      ellipptimba (EWA). The toxicity of total alkaloid and Baogongteng C was evaluated
      and compared. The results indicated that Baogongteng A and Baogongteng C are the
      major toxic chemical compounds of the Erycibe species tested. The results also
      suggest EWA is cholinergic. Finally, in a subacute toxicity study of EWA,
      alterations observed with high dosage suggest that the liver and kidney could be
      the target organs of toxicity. 

PMID- 25073110
TI  - Exploring the coordination chemistry of 3,3'-di(picolinamoyl)-2,2'-bipyridine:
      one ligand, multiple nuclearities.
AB  - The syntheses, structures, and magnetic properties of three new coordination
      complexes, tetranuclear [Zn2L(3)(OAc)(OMe)]2.3MeOH.H2O (3), trinuclear
      [Ni3(L(3))3].6H2O (4), and a 1-D chain {[Cu2L(3)(OAc)2]2.H2O}n (6), of a
      polydentate, doubly deprotonated, 3,3'-disubstituted bipyridine ligand [L(3)](2-)
      are reported. The X-ray crystal structures demonstrate that the ditopic ligand
      provides a flexible N3 donor set for transition metal ions where each binding
      pocket shifts from fac to intermediate fac/mer to the mer isomer affording a Ni3
      triangle, a Zn4 tetramer, and a 1-D Cu(II) polymer, respectively. This variation
      in coordination preference is rationalized with the aim of designing future
      ligands with controlled coordination modes. Magnetic susceptibility studies on 4
      reveal it belongs to the rare family of ferromagnetically coupled [Ni3] clusters.
      In contrast, magnetic studies of the 1-D chain 6 reveal weak antiferromagnetic
      interactions due to the poor orbital overlap of the singly occupied Cu(II) d(x(2)
      y(2)) orbitals with the one-atom bridge that connects them along the Jahn-Teller
      distortion axis.

PMID- 25073111
TI  - Expression patterns of cytochrome P450 3B and 3C genes in model fish species.
AB  - Cytochrome P450 (CYP) 3 enzymes are highly expressed in detoxification organs and
      play an important role in xenobiotic metabolism. In fish, the CYP3 family is
      diversified and includes several subfamilies (CYP3B, CYP3C, and CYP3D) not found
      in mammals. The functional role and expression patterns of these novel genes are
      unknown. In this study, the expression patterns of novel teleost CYP3 genes were
      determined in medaka(Oryzias latipes; CYP3B4, CYP3B5, CYP3B6) and zebrafish
      (Danio rerio; CYP3C1, CYP3C2, CYP3C3, CYP3C4), two important model fish species.
      Expression was quantified with real time PCR in multiple internal organs from
      adult male and female fish. CYP3C gene expression was determined in zebrafish
      embryos. Expression in all organs was detected for all genes, except for CYP3B4
      in male organs. CYP3C1, CYP3C3, CYP3B4, CYP3B5, and CYP3B6 were more highly
      expressed in liver and/or intestine from at least one gender, suggesting a role
      in xenobiotic metabolism. Expression of CYP3C1 and CYP3B5 in olfactory rosette
      was comparable to liver. CYP3C1, CYP3C4, CYP3B5 and CYP3B6 expression was higher
      in the female organs; CYP3C2 and CYP3B5 were higher in testis. Estrogen and
      androgen response elements were found upstream of the start site of many of these
      genes raising the hypothesis that they are under steroid regulation. CYP3C1-3
      were expressed in all developmental stages examined and appear to be maternally
      deposited. The expression patterns suggest that some of these CYP genes are
      involved in xenobiotic metabolism. 

PMID- 25073113
TI  - Antibody-dependent SARS coronavirus infection is mediated by antibodies against
      spike proteins.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) still carries the
      potential for reemergence, therefore efforts are being made to create a vaccine
      as a prophylactic strategy for control and prevention. Antibody-dependent
      enhancement (ADE) is a mechanism through which dengue viruses, feline
      coronaviruses, and HIV viruses take advantage of anti-viral humoral immune
      responses to infect host target cells. Here we describe our observations of SARS
      CoV using ADE to enhance the infectivity of a HL-CZ human promonocyte cell line.
      Quantitative-PCR and immunofluorescence staining results indicate that SARS-CoV
      is capable of replication in HL-CZ cells, and of displaying virus-induced
      cytopathic effects and increased levels of TNF-alpha, IL-4 and IL-6 two days post
      infection. According to flow cytometry data, the HL-CZ cells also expressed
      angiotensin converting enzyme 2 (ACE2, a SARS-CoV receptor) and higher levels of
      the FcgammaRII receptor. We found that higher concentrations of anti-sera against
      SARS-CoV neutralized SARS-CoV infection, while highly diluted anti-sera
      significantly increased SARS-CoV infection and induced higher levels of
      apoptosis. Results from infectivity assays indicate that SARS-CoV ADE is
      primarily mediated by diluted antibodies against envelope spike proteins rather
      than nucleocapsid proteins. We also generated monoclonal antibodies against SARS
      CoV spike proteins and observed that most of them promoted SARS-CoV infection.
      Combined, our results suggest that antibodies against SARS-CoV spike proteins may
      trigger ADE effects. The data raise new questions regarding a potential SARS-CoV
      vaccine, while shedding light on mechanisms involved in SARS pathogenesis. 

PMID- 25073114
TI  - In vivo characterization of neural crest-derived fibro/adipogenic progenitor
      cells as a likely cellular substrate for craniofacial fibrofatty infiltrating
      disorders.
AB  - The cellular substrate underlying aberrant craniofacial connective tissue
      accumulation that occurs in disorders such as congenital infiltration of the face
      (CILF) remain elusive. Here we analyze the in vivo properties of a recently
      identified population of neural crest-derived CD31-:CD45-:alpha7-:Sca1+:PDGFRa+
      fibro/adipogenic progenitors (NCFAPs). In serial transplantation experiments in
      which NCFAPs were prospectively purified and transplanted into wild type mice,
      NCFAPs were found to be capable of self-renewal while keeping their adipogenic
      potential. NCFAPs constitute the main responsive FAP fraction following acute
      masseter muscle damage, surpassing the number of mesoderm-derived FAPs (MFAPs)
      during the regenerative response. Lastly, NCFAPs differentiate into adipocytes
      during muscle regeneration in response to pro-adipogenic systemic cues.
      Altogether our data indicate that NCFAPs are a population of stem/primitive
      progenitor cells primarily involved in craniofacial muscle regeneration that can
      cause tissue degeneration when the damage co-occurs with an obesity inducing
      diet. 

PMID- 25073112
TI  - Nodal signaling promotes a tumorigenic phenotype in human breast cancer.
AB  - The Ras-ERK pathway is deregulated in approximately a third of human cancers,
      particularly those of epithelial origin. In aggressive, triple-negative, basal
      like breast cancers, most tumors display increased MEK and ERK phosphorylation
      and exhibit a gene expression profile characteristic of Kras or EGFR mutant
      tumors; however, Ras family genetic mutations are uncommon in triple-negative
      breast cancer and EGFR mutations account for only a subset of these tumors.
      Therefore, the upstream events that activate MAPK signaling and promote tumor
      aggression in triple-negative breast cancers remain poorly defined. We have
      previously shown that a secreted TGF-beta family signaling ligand, Nodal, is
      expressed in breast cancer in correlation with disease progression. Here we
      highlight key findings demonstrating that Nodal is required in aggressive human
      breast cancer cells to activate ERK signaling and downstream tumorigenic
      phenotypes both in vitro and in vivo. Experimental knockdown of Nodal signaling
      downregulates ERK activity, resulting in loss of c-myc, upregulation of p27, G1
      cell cycle arrest, increased apoptosis and decreased tumorigenicity. The data
      suggest that ERK activation by Nodal signaling regulates c-myc and p27 proteins
      post-translationally and that this cascade is essential for aggressive breast
      tumor behavior in vivo. As the MAPK pathway is an important target for treating
      triple-negative breast cancers, upstream Nodal signaling may represent a
      promising target for breast cancer diagnosis and combined therapies aimed at
      blocking ERK pathway activation.

PMID- 25073115
TI  - Purification and characterization of a cellulolytic multienzyme complex produced
      by Neocallimastix patriciarum J11.
AB  - Understanding the roles of the components of the multienzyme complex of the
      anaerobial cellulase system, acting on complex substrates, is crucial to the
      development of efficient cellulase systems for industrial applications such as
      converting lignocellulose to sugars for bioethanol production. In this study, we
      purified the multienzyme complex of Neocallimastix patriciarum J11 from a broth
      through cellulose affinity purification. The multienzyme complex is composed of
      at least 12 comprised proteins, based on sodium dodecyl sulfate polyacrylamide
      gel electrophoresis. Eight of these constituents have demonstrated beta-glucanase
      activity on zymogram analysis. The multienzyme complex contained scaffoldings
      that respond to the gathering of the cellulolytic components. The levels and
      subunit ratio of the multienzyme complex from N. patriciarum J11 might have been
      affected by their utilized carbon sources, whereas the components of the
      complexes were consistent. The trypsin-digested peptides of six proteins were
      matched to the sequences of cellulases originating from rumen fungi, based on
      identification through liquid chromatography/mass spectrometry, revealing that at
      least three types of cellulase, including one endoglucanase and two
      exoglucanases, could be found in the multienzyme complex of N. patriciarum J11.
      The cellulolytic subunits could hydrolyze synergistically on both the internal
      bonds and the reducing and nonreducing ends of cellulose. Based on our research,
      our findings are the first to depict the composition of the multienzyme complex
      produced by N. patriciarum J11, and this complex is composed of scaffoldin and
      three types of cellulase. 

PMID- 25073116
TI  - A facile access to a novel NHC-stabilized silyliumylidene ion and C-H activation
      of phenylacetylene.
AB  - Taking advantage of two N-heterocyclic carbenes (NHCs), novel silyliumylidene
      ions 1a and 1b are prepared by a facile one-pot reaction of the corresponding
      dichlorosilanes with three equivalents of NHCs. For the first time, a C-H
      insertion reaction of phenylacetylene by a novel silyliumylidene ion is reported.
      The treatment of m-terphenyl substituted silyliumylidene ion 1a with three
      equivalents of phenylacetylene results in the formation of m-terphenyl
      substituted 1-alkenyl-1,1-dialkynylsilane 2.

PMID- 25073117
TI  - Severe gastric lesions due to Helicobacter pylori infection in two patients
      undergoing hemodialysis.

PMID- 25073119
TI  - Clinical relevance of post-transplant pharmacodynamic analysis of cyclosporine in
      renal transplantation.
AB  - Although therapeutic drug monitoring based on blood concentration has been widely
      implemented in transplant recipients treated with immunosuppressive agents,
      clinical adverse events such as rejection, infection or drug-induced toxicity
      caused by inappropriate dosage cannot be completely controlled. Development of an
      effective assay for optimized immunosuppression would be desirable, which can
      potentially lead to personalized medicine in renal transplantation. Cyclosporine
      (CSA) pharmacodynamic analysis using carboxyfluorescein diacetate succinimidyl
      ester (CFSE)-based T cell proliferation assay was examined in 66 kidney
      transplant recipients before and after transplantation. Two parameters, the 50%
      inhibitory concentration (IC50) and the percentage of T-cell proliferation values
      at the lower plateau (bottom), were compared with clinical events. A significant
      relation in CSA pharmacodynamic parameters was observed between pre- and post
      transplantation. Analysis of the association between clinical outcomes and
      pharmacodynamic parameters in post-transplant samples demonstrated the following
      findings: (i) cytomegalovirus (CMV)/varicella zoster virus (VZV) reactivation and
      CSA-induced nephrotoxicity were significantly associated with high sensitivity to
      CSA (low bottom or low IC50), (ii) acute T cell-mediated rejection (ATMR) was
      significantly related to low sensitivity to CSA (high bottom), and (iii) de novo
      human leukocyte antigen (HLA) antibody production was associated with lower
      bottom and IC50 values, although the elucidation of those mechanisms is still in
      progress. It was suggested that CSA pharmacodynamics applied at post
      transplantation would be useful for optimizing immunosuppressive therapy. 

PMID- 25073118
TI  - Structural basis of glycan interaction in gastroenteric viral pathogens.
AB  - A critical event in the life cycle of a virus is its initial attachment to host
      cells. This involves recognition by the viruses of specific receptors on the cell
      surface, including glycans. Viruses typically exhibit strain-dependent variations
      in recognizing specific glycan receptors, a feature that contributes
      significantly to cell tropism, host specificity, host adaptation and interspecies
      transmission. Examples include influenza viruses, noroviruses, rotaviruses, and
      parvoviruses. Both rotaviruses and noroviruses are well known gastroenteric
      pathogens that are of significant global health concern. While rotaviruses, in
      the family Reoviridae, are the major causative agents of life-threatening
      diarrhea in children, noroviruses, which belong to the Caliciviridae family,
      cause epidemic and sporadic cases of acute gastroenteritis across all age groups.
      Both exhibit enormous genotypic and serotypic diversity. Consistent with this
      diversity each exhibits strain-dependent variations in the types of glycans they
      recognize for cell attachment. This chapter reviews the current status of the
      structural biology of such strain-dependent glycan specificities in these two
      families of viruses. 

PMID- 25073121
TI  - Quasi-photonic crystal effect of TiCl3/electrolyte matrix in unipolar dye
      absorber devices.
AB  - Effectiveness of TiCl3 pre- and post-treatments on dye-sensitized solar cells
      (DSCs) and interfacial charge-transfer properties were investigated. It was
      confirmed that a yield of current collection was strongly dependent on the
      position of the TiCl3/electrolyte matrix in the DSC configuration. The
      interfacial charge-transfer properties were studied using thermionic emission
      diffusion process and electrochemical impedance spectroscopy analysis. The
      TiCl3/electrolyte matrix was considered to be a three-dimensional quasi-photonic
      crystal with a photonic band gap, which reinforces electric field and facilitates
      current collection from the TiCl3/electrolyte matrix to the FTO by accelerating
      electron motion, whereas the potential barrier blocks current collection from the
      TiO2 bulk region to the FTO and decreases current. 

PMID- 25073120
TI  - Combined immunotherapy with dendritic cells and cytokine-induced killer cells for
      malignant tumors: a systematic review and meta-analysis.
AB  - PURPOSE: A new strategy of adoptive and passive immunotherapy involves combining
      dendritic cells (DCs) with a subset of natural killer T lymphocytes termed
      cytokine-induced killer (CIK) cells. The objective of this systematic review and
      meta-analysis was to evaluate the safety and efficacy of DC-CIK therapy vs.
      placebo, no intervention, conventional treatments, or other complementary and
      alternative medicines for malignant tumors. METHOD: We searched PubMed, Medline,
      Embase, Cochrane, Wangfang, Weipu, CNKI databases and reference lists of
      articles. We selected randomized controlled trials of DC-CIK therapy vs. placebo,
      no intervention, conventional treatments, or other complementary and alternative
      medicines in patients with all types and stages of malignant tumor. Primary
      outcome measures were overall survival and treatment response. Secondary outcome
      measures were health-related quality of life (HRQoL) assessment, progression free
      survival (PFS), and adverse events. RESULTS: Six trials met our inclusion
      criteria. There was evidence that chemotherapy+DC-CIK increased the 2-year (RR
      2.88, 95% CI 1.38 to 5.99, P=0.005) and 3-year (RR 11.67, 95% CI 2.28 to 59.69,
      P=0.003) survival rates and progression free survival (RR 0.64, 95% CI 0.34 to
      0.94, P<0.0001) in patients with non-small cell lung cancer compared to those
      treated with chemotherapy alone. DC-CIK therapy appears to be well-tolerated by
      cancer patients and to improve post-treatment patient health related quality of
      life. CONCLUSION: DC-CIK immunotherapy is a safe and effective treatment for
      patients with malignant tumors. Further clinical trials to provide supportive
      evidence for the routine use of DC-CIK therapy in clinical practice are
      warranted.

PMID- 25073122
TI  - Sandwichlike magnesium silicate/reduced graphene oxide nanocomposite for enhanced
      Pb2+ and methylene blue adsorption.
AB  - A sandwichlike magnesium silicate/reduced graphene oxide nanocomposite (MgSi/RGO)
      with high adsorption efficiency of organic dye and lead ion was synthesized by a
      hydrothermal approach. MgSi nanopetals were formed in situ on both sides of RGO
      sheets. The nanocomposite with good dispersion of nanopetals exhibits a high
      specific surface area of 450 m(2)/g and a good mass transportation property.
      Compared to MgSi and RGO, the mechanical stability and adsorption capacity of the
      nanocomposite is significantly improved due to the synergistic effect. The
      maximum adsorption capacities for methylene blue and lead ion are 433 and 416
      mg/g, respectively. 

PMID- 25073123
TI  - Gracilaria lemaneiformis polysaccharide as integrin-targeting surface decorator
      of selenium nanoparticles to achieve enhanced anticancer efficacy.
AB  - The poor permeability of glioma parenchyma represents a major limit for
      antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP),
      which has a high binding affinity to alphavbeta3 integrin overexpressed in glioma
      cells, was employed in the present study to functionalize selenium nanoparticles
      (SeNPs) to achieve antiglioblastoma efficacy. GLP-SeNPs showed satisfactory size
      distribution, high stability, and selectivity between cancer and normal cells. In
      U87 glioma cell membrane, which has a high integrin expression level, GLP-SeNPs
      exhibited significantly higher cellular uptake than unmodified SeNPs. As
      expected, U87 cells exhibited a greater uptake of GLP-SeNPs than C6 cells with
      low integrin expression level. Furthermore, the internalization of GLP-SeNPs was
      inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular
      uptake into U87 cells and C6 cells occurred via alphavbeta3 integrin-mediated
      endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was
      enhanced significantly because of the induction of various apoptosis signaling
      pathways. Internalized GLP-SeNPs triggered intracellular reactive oxygen species
      downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance
      cell apoptosis. These findings suggest that surface decoration of nanomaterials
      with GLP could be an efficient strategy for design and preparation of
      glioblastoma targeting nanodrugs. 

PMID- 25073124
TI  - A real-time research platform to study vestibular implants with gyroscopic inputs
      in vestibular deficient subjects.
AB  - Researchers have succeeded in partly restoring damaged vestibular functionality
      in several animal models. Recently, acute interventions have also been
      demonstrated in human patients. Our previous work on a vestibular implant for
      humans used predefined stimulation patterns; here we present a research tool that
      facilitates motion-modulated stimulation. This requires a system that can process
      gyroscope measurements and send stimulation parameters to a hybrid vestibular
      cochlear implant in real-time. To match natural vestibular latencies, the time
      from sensor input to stimulation output should not exceed 6.5 ms. We describe a
      system based on National Instrument's CompactRIO platform that can meet this
      requirement and also offers floating point precision for advanced transfer
      functions. It is designed for acute clinical interventions, and is sufficiently
      powerful and flexible to serve as a development platform for evaluating
      prosthetic control strategies. Amplitude and pulse frequency modulation to
      predetermined functions or sensor inputs have been validated. The system has been
      connected to human patients, who each have received a modified MED-EL cochlear
      implant for vestibular stimulation, and patient tests are ongoing. 

PMID- 25073125
TI  - An efficient and compact compressed sensing microsystem for implantable neural
      recordings.
AB  - Multi-Electrode Arrays (MEA) have been widely used in neuroscience experiments.
      However, the reduction of their wireless transmission power consumption remains a
      major challenge. To resolve this challenge, an efficient on-chip signal
      compression method is essential. In this paper, we first introduce a signal
      dependent Compressed Sensing (CS) approach that outperforms previous works in
      terms of compression rate and reconstruction quality. Using a publicly available
      database, our simulation results show that the proposed system is able to achieve
      a signal compression rate of 8 to 16 while guaranteeing almost perfect spike
      classification rate. Finally, we demonstrate power consumption measurements and
      area estimation of a test structure implemented using TSMC 0.18 MUm process. We
      estimate the proposed system would occupy an area of around 200 MUm *300 MUm per
      recording channel, and consumes 0.27 MU W operating at 20 KHz . 

PMID- 25073126
TI  - A 2.4 GHz ULP reconfigurable asymmetric transceiver for single-chip wireless
      neural recording IC.
AB  - This paper presents a 2.4 GHz ultra-low-power (ULP) reconfigurable asymmetric
      transceiver and demonstrates its application in wireless neural recording.
      Fabricated in 0.13 MUm CMOS technology, the transceiver is optimized for sensor
      gateway communications within a star-shaped network, and supports both the sensor
      and gateway operation modes. Binary phase-shift keying (BPSK) modulation with
      high data rate (DR) of 1 to 8 Mbps is used in the uplink from sensor to gateway,
      while on-off keying (OOK) modulation with low DR of 100 kbps is adopted in the
      downlink. A fully integrated Class-E PA with moderate output power has also been
      proposed and achieves power efficiency of 53%. To minimize area usage, inductor
      reuse is adopted between PA and LNA, and eliminates the need of lossy T/R switch
      in the RF signal path. When used as sensor, the transceiver with frequency locked
      phase-locked loop (PLL) achieves TX (BPSK) power efficiency of 28% @ 0 dBm output
      power, and RX (OOK) sensitivity of -80 dBm @ 100 kbps while consuming only 780
      MUW . When configured as gateway, the transceiver achieves sensitivity levels of 
      92, -84.5, and -77 dBm for 1, 5, and 8 Mbps BPSK, respectively. The transceiver
      is integrated with an 8-channel neural recording front-end, and neural signals
      from a rat are captured to verify the system functionality. 

PMID- 25073127
TI  - A frequency shaping neural recorder with 3 pF input capacitance and 11 plus 4.5
      bits dynamic range.
AB  - This paper presents a frequency-shaping (FS) neural recording architecture and
      its implementation in a 0.13 MU m CMOS process. Compared with its conventional
      counterpart, the proposed architecture inherently rejects electrode offset,
      increases input impedance 5-10 fold, compresses neural data dynamic range (DR) by
      4.5-bit, simultaneously records local field potentials (LFPs) and extracellular
      spikes, and is more suitable for long-term recording experiments. Measured at a
      40 kHz sampling clock and +/- 0.6 V supply, the recorder consumes 50 MUW/ch, of
      which 22 MUW per FS amplifier, 24 MU W per buffer, 4 MU W per 11-bit successive
      approximation register analog-to-digital converter (SAR ADC). The input-referred
      noise for LFPs and extracellular spikes are 13 MU Vrms and 7 MUVrms,
      respectively, which are sufficient to achieve high-fidelity full-spectrum neural
      data. In addition, the designed recorder has a 3 pF input capacitance and allows
      " 11+4.5"-bit neural data DR without system saturation, where the extra 4.5-bit
      owes to the FS technique. Its figure-of-merit (FOM) based on data DR reaches 36.0
      fJ/conversion-step. 

PMID- 25073128
TI  - A digitally assisted, signal folding neural recording amplifier.
AB  - A novel signal folding and reconstruction scheme for neural recording
      applications that exploits the 1/f(n) characteristics of neural signals is
      described in this paper. The amplified output is 'folded' into a predefined range
      of voltages by using comparison and reset circuits along with the core amplifier.
      After this output signal is digitized and transmitted, a reconstruction algorithm
      can be applied in the digital domain to recover the amplified signal from the
      folded waveform. This scheme enables the use of an analog-to-digital convertor
      with less number of bits for the same effective dynamic range. It also reduces
      the transmission data rate of the recording chip. Both of these features allow
      power and area savings at the system level. Other advantages of the proposed
      topology are increased reliability due to the removal of pseudo-resistors, lower
      harmonic distortion and low-voltage operation. An analysis of the reconstruction
      error introduced by this scheme is presented along with a behavioral model to
      provide a quick estimate of the post reconstruction dynamic range. Measurement
      results from two different core amplifier designs in 65 nm and 180 nm CMOS
      processes are presented to prove the generality of the proposed scheme in the
      neural recording applications. Operating from a 1 V power supply, the amplifier
      in 180 nm CMOS has a gain of 54.2 dB, bandwidth of 5.7 kHz, input referred noise
      of 3.8 MUVrms and power dissipation of 2.52 MUW leading to a NEF of 3.1 in spike
      band. It exhibits a dynamic range of 66 dB and maximum SNDR of 43 dB in LFP band.
      It also reduces system level power (by reducing the number of bits in the ADC by
      2) as well as data rate to 80% of a conventional design. In vivo measurements
      validate the ability of this amplifier to simultaneously record spike and LFP
      signals. 

PMID- 25073129
TI  - Programmable ExG biopotential front-end IC for wearable applications.
AB  - This paper presents a configurable CMOS integrated circuit front-end for the
      recording of a wide range of biopotentials (ExG). The system offers a choice
      between a single-differential or double-differential recording channel topology,
      wide continuously adjustable gain range (37-66 dB), selectable CMOS or BJT input
      stages, offset compensation, differential and buffered single-ended voltage
      output. Measured results from a prototype manufactured in 0.35 MUm CMOS
      technology are presented. Practical recording examples of the electrocardiogram
      (ECG) and electromyogram (EMG) confirm its operation. The chip consumes between
      110 and 324 MUW depending on configuration, occupies a core area of 0.16 mm(2),
      achieves a CMRR > 97 dB , and 21 nV/?Hz input-referred noise. The chip is suited
      for combination with a microcontroller in long-term wearable physiological
      sensing applications. 

PMID- 25073130
TI  - High-power CMOS current driver with accurate transconductance for electrical
      impedance tomography.
AB  - Current drivers are fundamental circuits in bioimpedance measurements including
      electrical impedance tomography (EIT). In the case of EIT, the current driver is
      required to have a large output impedance to guarantee high current accuracy over
      a wide range of load impedance values. This paper presents an integrated current
      driver which meets these requirements and is capable of delivering large
      sinusoidal currents to the load. The current driver employs a differential
      architecture and negative feedback, the latter allowing the output current to be
      accurately set by the ratio of the input voltage to a resistor value. The circuit
      was fabricated in a 0.6- MUm high-voltage CMOS process technology and its core
      occupies a silicon area of 0.64 mm (2) . It operates from a +/- 9 V power supply
      and can deliver output currents up to 5 mA p-p. The accuracy of the maximum
      output current is within 0.41% up to 500 kHz, reducing to 0.47% at 1 MHz with a
      total harmonic distortion of 0.69%. The output impedance is 665 k Omega at 100
      kHz and 372 k Omega at 500 kHz. 

PMID- 25073132
TI  - Introduction to the special issue on ultrasonics and ferroelectrics.
AB  - The sixteen articles in this special section were presented at the 2013 IEEE
      Ultrasonics, Ferroelectrics, and Frequency Control (UFFC) Symposium that was held
      in Prague, the Czech Republic, from July 21-25, 2013.

PMID- 25073131
TI  - The influence of sound generator associated with conventional amplification for
      tinnitus control: randomized blind clinical trial.
AB  - Hearing aids with an integrated sound generator have been used to enhance the
      treatment of tinnitus. The main aim of this study was to verify whether the
      combined use of amplification and sound generator is more effective than
      conventional amplification alone in reducing tinnitus annoyance by means of the
      use of a new hearing aid with an integrated sound generator. A total of 49
      patients underwent a blind randomized clinical trial. Tinnitus annoyance was
      measured by Tinnitus Handicap Inventory and numerical scales, and psychoacoustic
      measures of tinnitus were also performed. The sound generator was set at the
      lowest intensity capable of providing relief from tinnitus. Results showed that
      62.5% of the patients presented a reduction in tinnitus annoyance in the combined
      fitting group and in the group with amplification alone, 78% showed a reduction.
      This difference between the groups was not statistically significant. 

PMID- 25073133
TI  - Fourier-domain beamforming: the path to compressed ultrasound imaging.
AB  - Sonography techniques use multiple transducer elements for tissue visualization.
      Signals received at each element are sampled before digital beamforming. The
      sampling rates required to perform high-resolution digital beamforming are
      significantly higher than the Nyquist rate of the signal and result in
      considerable amount of data that must be stored and processed. A recently
      developed technique, compressed beamforming, based on the finite rate of
      innovation model, compressed sensing (CS), and Xampling ideas, allows a reduction
      in the number of samples needed to reconstruct an image comprised of strong
      reflectors. A drawback of this method is its inability to treat speckle, which is
      of significant importance in medical imaging. Here, we build on previous work and
      extend it to a general concept of beamforming in frequency. This allows
      exploitation of the low bandwidth of the ultrasound signal and bypassing of the
      oversampling dictated by digital implementation of beamforming in time. By using
      beamforming in frequency, the same image quality is obtained from far fewer
      samples. We next present a CS technique that allows for further rate reduction,
      using only a portion of the beamformed signal's bandwidth. We demonstrate our
      methods on in vivo cardiac data and show that reductions up to 1/28 of the
      standard beamforming rates are possible. Finally, we present an implementation on
      an ultrasound machine using sub-Nyquist sampling and processing. Our results
      prove that the concept of sub-Nyquist processing is feasible for medical
      ultrasound, leading to the potential of considerable reduction in future
      ultrasound machines' size, power consumption, and cost. 

PMID- 25073135
TI  - Multimodal detection of iron oxide nanoparticles in rat lymph nodes using
      magnetomotive ultrasound imaging and magnetic resonance imaging.
AB  - Detection and removal of sentinel lymph nodes (SLN) is important in the diagnosis
      and treatment of cancer. The SLN is the first regional lymph node draining the
      primary tumor, and if the cancer has spread, it is most likely to find metastases
      in the SLN. In this study, we have for the first time been able to image the very
      same contrast agent, superparamagnetic iron oxide nanoparticles (SPIO-NPs), in
      rat SLNs by using both our frequency- and phase-gated magnetomotive ultrasound
      (MMUS) algorithm and conventional magnetic resonance imaging (MRI); MMUS post
      mortem, MRI in vivo. For both higher NP-concentration and smaller NPs, we found
      that the MMUS data showed a larger magnetomotive displacement (1.56 +/- 0.43 and
      1.94 +/- 0.54 times larger, respectively) and that the MR-images were affected to
      a higher degree. The MMUS displacement also increased with lower excitation
      frequency (1.95 +/- 0.64 times larger for 5 Hz compared with 15 Hz) and higher
      excitation voltage (2.95 +/- 1.44 times larger for 30 V compared with 10 V). The
      results show that MMUS has potential to be used as bedside guidance during SLN
      surgery, imaging the same particles that were used in prior staging with other
      imaging techniques. 

PMID- 25073134
TI  - Transthoracic ultrafast Doppler imaging of human left ventricular hemodynamic
      function.
AB  - Heart diseases can affect intraventricular blood flow patterns. Real-time imaging
      of blood flow patterns is challenging because it requires both a high frame rate
      and a large field of view. To date, standard Doppler techniques can only perform
      blood flow estimation with high temporal resolution within small regions of
      interest. In this work, we used ultrafast imaging to map in 2-D human left
      ventricular blood flow patterns during the whole cardiac cycle. Cylindrical waves
      were transmitted at 4800 Hz with a transthoracic phased-array probe to achieve
      ultrafast Doppler imaging of the left ventricle. The high spatio-temporal
      sampling of ultrafast imaging permits reliance on a much more effective wall
      filtering and increased sensitivity when mapping blood flow patterns during the
      pre-ejection, ejection, early diastole, diastasis, and late diastole phases of
      the heart cycle. The superior sensitivity and temporal resolution of ultrafast
      Doppler imaging makes it a promising tool for the noninvasive study of
      intraventricular hemodynamic function. 

PMID- 25073136
TI  - Efficient immersion imaging of components with nonplanar surfaces.
AB  - Ultrasonic array inspection of a component with a nonplanar surface can be
      achieved in immersion using a liquid layer to couple ultrasonic waves from an
      array probe into a solid structure. This paper presents an efficient way to
      compute the appropriate element time delays in immersion without compromising the
      measurement accuracy. In the proposed imaging process, the surface geometry is
      first measured ultrasonically by forming an image of the component surface in the
      couplant. This leads to a set of discrete points that define the surface profile
      of the component. The propagation time from an array element to a point in the
      component is then determined by a grid search of candidate ray-paths through each
      surface point to identify the one that yields the shortest traveling time.
      Propagation times in the component are first generated on a coarse mesh of points
      and then these values are linearly interpolated to find the propagation time to
      each image pixel. The computed propagation times are finally used to reconstruct
      an image of the component interior. An analytical model is developed to determine
      a relationship between estimated propagation time errors and their effect on the
      array inspection in terms of signal amplitude from a reflector. For nominally
      normal incidence inspection of a metallic component with a minimum surface radius
      of 30 wavelengths immersed in water, it is found that the surface of the
      component can be adequately described by points spaced by one wavelength and that
      delays can be computed on a coarse grid of points spaced at 3 wavelengths. With
      these parameters, the reduction in amplitude of a point target in the component
      is shown to be less than 1 dB. 

PMID- 25073137
TI  - Acoustic black holes: recent developments in the theory and applications.
AB  - Acoustic black holes are relatively new physical objects that have been
      introduced and investigated mainly during the last decade. They can absorb almost
      100% of the incident wave energy, and this makes them very attractive for such
      traditional engineering applications as vibration damping in different
      engineering structures and sound absorption in gases and liquids. They also could
      be useful for some ultrasonic devices using Lamb wave propagation to provide
      anechoic termination for such waves. So far, acoustic black holes have been
      investigated mainly for flexural waves in thin plates, for which the required
      gradual changes in local wave velocity with distance can be easily achieved by
      changing the plates' local thickness. The present paper provides a brief review
      of the theory of acoustic black holes, including their comparison with optic
      black holes introduced about five years ago. Review is also given of the recent
      experimental work carried out at Loughborough University on damping structural
      vibrations using the acoustic black hole effect. This is followed by the
      discussion on potential applications of the acoustic black hole effect for sound
      absorption in air.

PMID- 25073138
TI  - Gigahertz acoustic wave velocity measurement in GaN single crystals considering
      acousto-electric effect.
AB  - The resistivity-frequency characteristics of longitudinal wave velocities
      propagating parallel to the c-axis in a GaN single crystal were theoretically
      estimated by considering the piezoelectric acousto-electric effect. The
      temperature and frequency dependences of longitudinal and shear wave velocities
      in conductive and semiconductive GaN single-crystal samples were experimentally
      investigated by Brillouin scattering. The temperature dependence of longitudinal
      and shear wave velocities had a linear tendency in the conductive sample, whereas
      in the semiconductive sample, those had a similar tendency to the predicted
      velocity changes resulting from the piezoelectric stiffening effect. However, the
      temperature dependence of shear wave velocity, which does not possess
      piezoelectric coupling, had a tendency similar to that of the longitudinal wave
      in the semiconductive sample, unexpectedly. The frequency dependence of
      longitudinal wave velocities in the semiconductive sample had a tendency similar
      to the predicted velocity changes resulting from the piezoelectric stiffening
      effect.

PMID- 25073139
TI  - Focusing capability of a phononic crystal based on a hollow metallic structure.
AB  - The dispersion curves of a phononic crystal (PC) based on a hollow metallic
      structure are presented. They exhibit a negative refraction dispersion branch and
      perfect refractive index matching with the surrounding water, leading to focusing
      capability. Numerical and experimental results are reported for a flat PC lens.
      The characteristics of the focal spot (intensity, dimensions, etc.) are
      numerically and experimentally investigated with the goal of finding the
      frequency of the optimal imaging performance. 

PMID- 25073140
TI  - Sputter deposition of stress-controlled piezoelectric AlN and AlScN films for
      ultrasonic and energy harvesting applications.
AB  - This paper reports on the deposition and characterization of piezoelectric AlN
      and AlXSc1-XN layers. Characterization methods include XRD, SEM, active thermo
      probe, pulse echo, and piezometer measurements. A special focus is on the
      characterization of AlN regarding the mechanical stress in the films. The stress
      in the films changed between -2.2 GPa (compressive) and 0.2 GPa (tensile) and
      showed a significant dependence on film thickness. The cause of this behavior is
      presumed to be the different mean grain sizes at different film thicknesses, with
      bigger mean grain sizes at higher thicknesses. Other influences on film stress
      such as the sputter pressure or the pulse mode are presented. The deposition of
      gradient layers using those influences allowed the adjustment of film stress
      while retaining the piezoelectric properties. 

PMID- 25073141
TI  - A promising method to derive the temperature coefficients of material constants
      of SAW and BAW materials. first application to LGS.
AB  - Langasite (LGS) is a promising material for SAW applications at high temperature.
      However, the temperature coefficients of LGS material constants are not accurate
      enough to perform reliable simulations, and therefore to make good use of
      available design tools, above 300 degrees C. In the first part of the paper, we
      describe a new possible way to derive these coefficients in a wider temperature
      range. The method is based on Simulated Annealing, a well-known optimization
      algorithm. The algorithm converges toward a set of optimized temperature
      coefficients of the stiffness constants which are used to perform accurate
      simulations up to at least 800 degrees C. In the second part, a deeper analysis
      of the algorithm outputs demonstrates some of its strengths but also some of its
      main limitations. Possible solutions are described to predict and then improve
      the accuracy of the optimized coefficient values. In particular, one solution
      making use of additional BAW target curves is tested. A promising solution to
      extend the optimization to the temperature coefficients of piezoelectric
      constants is also discussed. 

PMID- 25073142
TI  - High-temperature piezoelectric crystals ReCa4O(BO3)3: a review.
AB  - High-temperature sensors are desirable for structural health monitoring and/or
      nondestructive evaluation of next-generation turbines, more efficient jet
      engines, and the furnace components of electrical power plants. Of all the
      investigated high-temperature piezoelectric materials, rare-earth calcium
      oxyborate crystals ReCa4O(BO3)3 (ReCOB, Re: rare-earth) exhibit attractive
      advantages for high-temperature piezoelectric sensing. In this paper, the
      electroelastic properties of different ReCOB piezoelectric crystals are
      investigated. The crosstalk between various vibration modes are discussed, from
      which the optimized crystal cuts are achieved. Furthermore, temperature
      dependences of the electrical resistivity, dielectric, elastic, piezoelectric,
      and electromechanical properties of ReCOB crystals are studied. Finally, the
      thermal properties, including thermal expansion, specific heat, and thermal
      conductivity at elevated temperatures are studied and compared with commercially
      available high-temperature piezoelectric crystals. 

PMID- 25073143
TI  - Modeling of efficient solid-state cooler on layered multiferroics.
AB  - We have developed theoretical foundations for the design and optimization of a
      solid-state cooler working through caloric and multicaloric effects. This
      approach is based on the careful consideration of the thermodynamics of a layered
      multiferroic system. The main section of the paper is devoted to the derivation
      and solution of the heat conduction equation for multiferroic materials. On the
      basis of the obtained results, we have performed the evaluation of the
      temperature distribution in the refrigerator under periodic external fields. A
      few practical examples are considered to illustrate the model. It is demonstrated
      that a 40-mm structure made of 20 ferroic layers is able to create a temperature
      difference of 25K. The presented work tries to address the whole hierarchy of
      physical phenomena to capture all of the essential aspects of solid-state
      cooling. 

PMID- 25073144
TI  - Nano-domains and related phenomena in congruent lithium tantalate single crystals
      studied by scanning nonlinear dielectric microscopy.
AB  - Nanodomains and their related phenomena in congruent lithium tantalate (CLT)
      single crystals are studied using scanning nonlinear dielectric microscopy
      (SNDM). We carried out two specific investigations: super higher order nonlinear
      dielectric spectroscopy studies on thick multi-domain congruent CLT single
      crystals and electrical conduction in nanodomains in thin CLT single crystals.
      First, without using a special sharp tip, we achieve improved lateral resolution
      in SNDM through the measurement of super higher order nonlinearity up to the
      fourth order. We also found a marked enhancement of nonlinear dielectric
      constants when the applied tip-sample voltage exceeded a particular threshold
      value. This is due to domain nucleation activated by a huge electric field under
      the tip. Low frequencies (less than a few hundred hertz) do not enhance
      nonlinearity. An effectively lower electric field caused by ion conduction in the
      sample under the tip is a possible reason for the frequency-dependent
      characteristics of the enhanced nonlinearity for the applied voltage. Finally,
      electrical current flow behavior was investigated for nanodomains formed in a
      thin CLT single-crystal plate. When the nanodomains are relatively large, with
      diameters of about 100 nm, current flow is detected along the domain wall.
      However, when the nanodomains were about 40 nm or smaller in size, current flowed
      through the entire nanodomain. Schottky-like rectifying behavior was observed. A
      clear temperature dependence of the current is found, indicating that the
      conduction mechanism for nanodomains in CLT may involve thermally activated
      carrier hopping.

PMID- 25073145
TI  - Using the methods of radiospectroscopy (EPR, NMR) to study the nature of the
      defect structure of solid solutions based on lead zirconate titanate (PZT).
AB  - The nature of intrinsic and impurity point defects in lead zirconate titanate
      (PZT) ceramics has been explored. Using electron paramagnetic resonance (EPR),
      nuclear magnetic resonance (NMR), and X-ray photoelectron spectroscopy (XPS)
      methods, several impurity sites have been identified in the materials, including
      the Fe(3+)-oxygen vacancy (VO) complex and Pb ions. Both of these centers are
      incorporated into the PZT lattice. The Fe(3+) -VO paramagnetic complex serves as
      a sensitive probe of the local crystal field in the ceramic; the symmetry of this
      defect roughly correlates with PZT phase diagram as the composition is varied
      from PbTiO3 to PbZrO3. NMR spectra (207)Pb in PbTiO3, PbZrO3, and PZT with iron
      content from 0 to 0.4 wt% showed that increasing the iron concentration leads to
      a distortion of the crystal structure and to improvement of the electrophysical
      parameters of the piezoceramics. This is due to the formation of a phase which
      has a higher symmetry, but at high concentrations of iron (>0.4 wt%), it leads to
      sharp degradation of electrophysical parameters.

PMID- 25073146
TI  - Top orthogonal to bottom electrode (TOBE) 2-D CMUT arrays for 3-D photoacoustic
      imaging.
AB  - Top orthogonal to bottom electrode (TOBE) capacitive micromachined ultrasound
      transducers (CMUTs) are a new transducer architecture that permits large 2-D
      arrays to be addressed using row-column addressing. Here, we demonstrate the
      feasibility of 3-D photoacoustic imaging using N laser pulses and N receive
      channels. We used a synthetic aperture approach to simulate a large 2 X 2 cm
      array using a smaller die. A hair phantom in an oil immersion medium was excited
      by a laser, and the received signal was dynamically focused to obtain high
      resolution images. We found the TOBE CMUT to have a center frequency of 3.7 MHz
      with a bandwidth of 3.9 MHz. Lateral and axial resolutions were 866 ?m and 296
      MUm, respectively.

PMID- 25073147
TI  - Noninvasive estimation of 2-D pressure gradients in steady flow using ultrasound.
AB  - A noninvasive method for estimating 2-D pressure gradients from ultrasound vector
      velocity data is presented. It relies on vector velocity fields acquired using
      the transverse oscillation method during steady flow conditions. The pressure
      gradients are calculated from the velocity fields using the Navier-Stokes
      equations. Scans of a carotid bifurcation phantom with a 70% constriction are
      performed using a linear transducer connected to a scanner. The performance of
      the estimator is evaluated by comparing its results to those of a computational
      fluid dynamics model of the carotid bifurcation phantom. The geometry of the
      model is determined from magnetic resonance imaging. The presented study is
      conducted assuming steady flow using velocity data acquired at 18 frames per
      second. The proposed method shows pressure gradients at the constricted region
      from -8 kPa/m to 9 kPa/m, with a maximum bias of -7% for the axial component and 
      8% for the lateral component. The relative standard deviation of the estimator is
      5% (axial component) and 30% (lateral component) when studying the pressure
      gradient across the constriction using 3 velocity frames per pressure estimate.
      The study shows that 2-D pressure gradients can be achieved noninvasively using
      ultrasound data in a constant flow environment. 

PMID- 25073148
TI  - SNR-dependent coherence-based adaptive imaging for high-frame-rate ultrasonic and
      photoacoustic imaging.
AB  - This paper introduces the SNR-dependent coherence factor (CF), which can be used
      for adaptive side lobe suppression in ultrasound (US) and photoacoustic (PA)
      imaging. Previous methods employed the minimum-variance distortionless response
      (MVDR)-based CF to achieve remarkable resolution improvement (by MVDR) and to
      suppress side lobes (by CF). However, the SNR is often low when using an
      unfocused acoustic beam (e.g., high-frame-rate imaging) and in PA imaging
      (limited laser energy), giving such an approach suboptimal performance in these
      applications because noise also lowers the coherence and thus affects the
      effectiveness of the side lobe suppression by these CF-based methods. To overcome
      this problem, the proposed method takes into account the local SNR in the CF
      formulation so that the contrast can be restored even when the SNR is low. We
      tested this method with both high-frame-rate US imaging and PA imaging.
      Simulations show that the proposed method performs well even when the SNR is as
      low as -10 dB. Compared with the conventional CF, the contrast (CR) and contrast
      to-noise ratio (CNR) in clinical US imaging can be improved by an average of
      27.2% in CR and 11.1% in CNR with the proposed method, whereas in PA imaging, the
      lateral resolution could be restored and the image contrast was elevated by 17
      dB. 

PMID- 25073149
TI  - Mother centrioles do a cartwheel to produce just one daughter.
AB  - In this issue of Developmental Cell, Fong et al. (2014) present evidence for a
      model of centriole duplication whereby the cartwheel-the starting building block
      in centriole biogenesis-assembles within the lumen of the mother centriole before
      templating the daughter centriole to ensure a single duplication event per cell
      cycle.

PMID- 25073150
TI  - Sizing up lung stem cells.
AB  - Mammalian lungs are comprised of conducting airways and alveoli. How the distinct
      epithelial linings of these two zones are differentially specified and maintained
      is not fully understood. In this issue of Developmental Cell, two groups find
      critical roles for the Hippo pathway in regulation of lung progenitor cell
      differentiation. 

PMID- 25073151
TI  - A time and place for understanding neural stem cell specification.
AB  - The regulation of neural stem cells is key to their use for repair. Reporting in
      this issue of Developmental Cell, Dirian et al. (2014) identify an adult neural
      stem cell population surprisingly distinct in Notch independence, lack of radial
      glia hallmarks, and late contribution to neurogenesis in a strikingly region
      specific manner.

PMID- 25073152
TI  - A whiter shade of gray: HIF and coordination of angiogenesis with postnatal
      myelination.
AB  - Oligodendrocyte precursor cells are the primary source of myelinating
      oligodendrocytes in the neonatal CNS. In a recent issue of Cell, Yuen and
      coworkers (2014) show that hypoxia-inducible factors and Wnt7a/7b act in
      developing white matter, promoting angiogenesis in anticipation of the metabolic
      demands of oligogenesis, before finally allowing precursor differentiation. 

PMID- 25073153
TI  - A long noncoding way to alternative splicing in plant development.
AB  - In this issue of Developmental Cell, Bardou et al. (2014) elucidate how long,
      highly structured noncoding RNAs control alternative splicing regulators that
      specifically mediate the action of the hormone auxin in the promotion of lateral
      root growth in Arabidopsis.

PMID- 25073154
TI  - Long noncoding RNA modulates alternative splicing regulators in Arabidopsis.
AB  - Alternative splicing (AS) of pre-mRNA represents a major mechanism underlying
      increased transcriptome and proteome complexity. Here, we show that the nuclear
      speckle RNA-binding protein (NSR) and the AS competitor long noncoding RNA (or
      ASCO-lncRNA) constitute an AS regulatory module. AtNSR-GFP translational fusions
      are expressed in primary and lateral root (LR) meristems. Double Atnsr mutants
      and ASCO overexpressors exhibit an altered ability to form LRs after auxin
      treatment. Interestingly, auxin induces a major change in AS patterns of many
      genes, a response largely dependent on NSRs. RNA immunoprecipitation assays
      demonstrate that AtNSRs interact not only with their alternatively spliced mRNA
      targets but also with the ASCO-RNA in vivo. The ASCO-RNA displaces an AS target
      from an NSR-containing complex in vitro. Expression of ASCO-RNA in Arabidopsis
      affects the splicing patterns of several NSR-regulated mRNA targets. Hence,
      lncRNA can hijack nuclear AS regulators to modulate AS patterns during
      development.

PMID- 25073155
TI  - Roles for Pbp1 and caloric restriction in genome and lifespan maintenance via
      suppression of RNA-DNA hybrids.
AB  - Intergenic transcription within repetitive loci such as the ribosomal DNA (rDNA)
      repeats of yeast commonly triggers aberrant recombination. Major mechanisms
      suppressing aberrant rDNA recombination rely on chromatin silencing or RNAPII
      repression at intergenic spacers within the repeats. We find ancient processes
      operating at rDNA intergenic spacers and other loci to maintain genome stability
      via repression of RNA-DNA hybrids. The yeast Ataxin-2 protein Pbp1 binds
      noncoding RNA, suppresses RNA-DNA hybrids, and prevents aberrant rDNA
      recombination. Repression of RNA-DNA hybrids in Pbp1-deficient cells through
      RNaseH overexpression, deletion of the G4DNA-stabilizing Stm1, or caloric
      restriction operating via RNaseH/Pif1 restores rDNA stability. Pbp1 also limits
      hybrids at non-rDNA G4DNA loci including telomeres. Moreover, cells lacking Pbp1
      have a short replicative lifespan that is extended upon hybrid suppression. Thus,
      we find roles for Pbp1 in genome maintenance and reveal that caloric restriction
      counteracts Pbp1 deficiencies by engaging RNaseH and Pif1.

PMID- 25073156
TI  - Global programmed switch in neural daughter cell proliferation mode triggered by
      a temporal gene cascade.
AB  - During central nervous system (CNS) development, progenitors typically divide
      asymmetrically, renewing themselves while budding off daughter cells with more
      limited proliferative potential. Variation in daughter cell proliferation has a
      profound impact on CNS development and evolution, but the underlying mechanisms
      remain poorly understood. We find that Drosophila embryonic neural progenitors
      (neuroblasts) undergo a programmed daughter proliferation mode switch, from
      generating daughters that divide once (type I) to generating neurons directly
      (type 0). This typeI>0 switch is triggered by activation of Dacapo (mammalian
      p21(CIP1)/p27(KIP1)/p57(Kip2)) expression in neuroblasts. In the thoracic region,
      Dacapo expression is activated by the temporal cascade (castor) and the Hox gene
      Antennapedia. In addition, castor, Antennapedia, and the late temporal gene
      grainyhead act combinatorially to control the precise timing of neuroblast cell
      cycle exit by repressing Cyclin E and E2f. This reveals a logical principle
      underlying progenitor and daughter cell proliferation control in the Drosophila
      CNS.

PMID- 25073159
TI  - Remote detection of photoplethysmographic systolic and diastolic peaks using a
      digital camera.
AB  - We present a new method for measuring photoplethysmogram signals remotely using
      ambient light and a digital camera that allows for accurate recovery of the
      waveform morphology (from a distance of 3 m). In particular, we show that the
      peak-to-peak time between the systolic peak and diastolic peak/inflection can be
      automatically recovered using the second-order derivative of the remotely
      measured waveform. We compare measurements from the face with those captured
      using a contact fingertip sensor and show high agreement in peak and interval
      timings. Furthermore, we show that results can be significantly improved using
      orange, green, and cyan color channels compared to the tradition red, green, and
      blue channel combination. The absolute error in interbeat intervals was 26 ms and
      the absolute error in mean systolic-diastolic peak-to-peak times was 12 ms. The
      mean systolic-diastolic peak-to-peak times measured using the contact sensor and
      the camera were highly correlated, rho = 0.94 (p 0.001). The results were
      obtained with a camera frame-rate of only 30 Hz. This technology has significant
      potential for advancing healthcare. 

PMID- 25073157
TI  - High-resolution temporal analysis reveals a functional timeline for the molecular
      regulation of cytokinesis.
AB  - To take full advantage of fast-acting temperature-sensitive mutations, thermal
      control must be extremely rapid. We developed the Therminator, a device capable
      of shifting sample temperature in ~17 s while simultaneously imaging cell
      division in vivo. Applying this technology to six key regulators of cytokinesis,
      we found that each has a distinct temporal requirement in the Caenorhabditis
      elegans zygote. Specifically, myosin-II is required throughout cytokinesis until
      contractile ring closure. In contrast, formin-mediated actin nucleation is only
      required during assembly and early contractile ring constriction. Centralspindlin
      is required to maintain division after ring closure, although its GAP activity is
      only required until just prior to closure. Finally, the chromosomal passenger
      complex is required for cytokinesis only early in mitosis, but not during
      metaphase or cytokinesis. Together, our results provide a precise functional
      timeline for molecular regulators of cytokinesis using the Therminator, a
      powerful tool for ultra-rapid protein inactivation.

PMID- 25073160
TI  - Robotic adherent cell injection for characterizing cell-cell communication.
AB  - Compared to robotic injection of suspended cells (e.g., embryos and oocytes),
      fewer attempts were made to automate the injection of adherent cells (e.g.,
      cancer cells and cardiomyocytes) due to their smaller size, highly irregular
      morphology, small thickness (a few micrometers thick), and large variations in
      thickness across cells. This paper presents a robotic system for automated
      microinjection of adherent cells. The system is embedded with several new
      capabilities: automatically locating micropipette tips; robustly detecting the
      contact of micropipette tip with cell culturing surface and directly with cell
      membrane; and precisely compensating for accumulative positioning errors. These
      new capabilities make it practical to perform adherent cell microinjection truly
      via computer mouse clicking in front of a computer monitor, on hundreds and
      thousands of cells per experiment (versus a few to tens of cells as state of the
      art). System operation speed, success rate, and cell viability rate were
      quantitatively evaluated based on robotic microinjection of over 4000 cells. This
      paper also reports the use of the new robotic system to perform cell-cell
      communication studies using large sample sizes. The gap junction function in a
      cardiac muscle cell line (HL-1 cells), for the first time, was quantified with
      the system. 

PMID- 25073158
TI  - EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone
      H4.
AB  - Posttranslational modifications of histones play fundamental roles in many
      biological functions. Specifically, histone H4-K20 methylation is critical for
      DNA synthesis and repair. However, little is known about how these functions are
      regulated by the upstream stimuli. Here, we identify a tyrosine phosphorylation
      site at Y72 of histone H4, which facilitates recruitment of histone
      methyltransferases (HMTases), SET8 and SUV4-20H, to enhance its K20 methylation,
      thereby promoting DNA synthesis and repair. Phosphorylation-defective histone H4
      mutant is deficient in K20 methylation, leading to reduced DNA synthesis, delayed
      cell cycle progression, and decreased DNA repair ability. Disrupting the
      interaction between epidermal growth factor receptor (EGFR) and histone H4 by Y72
      peptide significantly reduced tumor growth. Furthermore, EGFR expression
      clinically correlates with histone H4-Y72 phosphorylation, H4-K20
      monomethylation, and the Ki-67 proliferation marker. These findings uncover a
      mechanism by which EGFR transduces signal to chromatin to regulate DNA synthesis
      and repair.

PMID- 25073161
TI  - Reconstruction of fluorophore concentration variation in dynamic fluorescence
      molecular tomography.
AB  - Dynamic fluorescence molecular tomography (DFMT) is a potential approach for drug
      delivery, tumor detection, diagnosis, and staging. The purpose of DFMT is to
      quantify the changes of fluorescent agents in the bodies, which offer important
      information about the underlying physiological processes. However, the
      conventional method requires that the fluorophore concentrations to be
      reconstructed are stationary during the data collection period. As thus, it
      cannot offer the dynamic information of fluorophore concentration variation
      within the data collection period. In this paper, a method is proposed to
      reconstruct the fluorophore concentration variation instead of the fluorophore
      concentration through a linear approximation. The fluorophore concentration
      variation rate is introduced by the linear approximation as a new unknown term to
      be reconstructed and is used to obtain the time courses of fluorophore
      concentration. Simulation and phantom studies are performed to validate the
      proposed method. The results show that the method is able to reconstruct the
      fluorophore concentration variation rates and the time courses of fluorophore
      concentration with relative errors less than 0.0218. 

PMID- 25073162
TI  - Dynamic low-level context for the detection of mild traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) appears as low contrast lesions in magnetic
      resonance (MR) imaging. Standard automated detection approaches cannot detect the
      subtle changes caused by the lesions. The use of context has become integral for
      the detection of low contrast objects in images. Context is any information that
      can be used for object detection but is not directly due to the physical
      appearance of an object in an image. In this paper, new low-level static and
      dynamic context features are proposed and integrated into a discriminative voxel
      level classifier to improve the detection of mTBI lesions. Visual features,
      including multiple texture measures, are used to give an initial estimate of a
      lesion. From the initial estimate novel proximity and directional distance,
      contextual features are calculated and used as features for another classifier.
      This feature takes advantage of spatial information given by the initial lesion
      estimate using only the visual features. Dynamic context is captured by the
      proposed posterior marginal edge distance context feature, which measures the
      distance from a hard estimate of the lesion at a previous time point. The
      approach is validated on a temporal mTBI rat model dataset and shown to have
      improved dice score and convergence compared to other state-of-the-art
      approaches. Analysis of feature importance and versatility of the approach on
      other datasets are also provided. 

PMID- 25073163
TI  - Detection of abnormal cardiac activity using principal component analysis--a
      theoretical study.
AB  - Electrogram-guided ablation has been recently developed for allowing better
      detection and localization of abnormal atrial activity that may be the source of
      arrhythmogeneity. Nevertheless, no clear indication for the benefit of using
      electrograms guided ablation over empirical ablation was established thus far,
      and there is a clear need of improving the localization of cardiac arrhythmogenic
      targets for ablation. In this paper, we propose a new approach for detection and
      localization of irregular cardiac activity during ablation procedures that is
      based on dimension reduction algorithms and principal component analysis (PCA).
      Using an 8*8 electrode array, our method produces manifolds that allow easy
      visualization and detection of possible arrhythmogenic ablation targets
      characterized by irregular conduction. We employ mathematical modeling and
      computer simulations to demonstrate the feasibility of the new approach for two
      well established arrhythmogenic sources for irregular conduction--spiral waves
      and patchy fibrosis. Our results show that the PCA method can differentiate
      between focal ectopic activity and spiral wave activity, as these two types of
      activity produce substantially different manifold shapes. Moreover, the technique
      allows the detection of spiral wave cores and their general meandering and
      drifting pattern. Fibrotic patches larger than 2 mm(2) could also be visualized
      using the PCA method, both for quiescent atrial tissue and for tissue exhibiting
      spiral wave activity. We envision that this method, contingent to further
      numerical and experimental validation studies in more complex, realistic
      geometrical configurations and with clinical data, can improve existing atrial
      ablation mapping capabilities, thus increasing success rates and optimizing
      arrhythmia management. 

PMID- 25073164
TI  - A joint QRS detection and data compression scheme for wearable sensors.
AB  - This paper presents a novel electrocardiogram (ECG) processing technique for
      joint data compression and QRS detection in a wireless wearable sensor. The
      proposed algorithm is aimed at lowering the average complexity per task by
      sharing the computational load among multiple essential signal-processing tasks
      needed for wearable devices. The compression algorithm, which is based on an
      adaptive linear data prediction scheme, achieves a lossless bit compression ratio
      of 2.286x. The QRS detection algorithm achieves a sensitivity (Se) of 99.64% and
      positive prediction (+P) of 99.81% when tested with the MIT/BIH Arrhythmia
      database. Lower overall complexity and good performance renders the proposed
      technique suitable for wearable/ambulatory ECG devices. 

PMID- 25073165
TI  - A graph-based method for detecting rare events: identifying pathologic cells.

PMID- 25073166
TI  - A visual-analytics system for railway safety management.
AB  - The working environment of railways is challenging and complex and often involves
      high-risk operations. These operations affect both the company staff and
      inhabitants of the towns and cities alongside the railway lines. To reduce the
      employees' and public's exposure to risk, railway companies adopt strategies
      involving trained safety personnel, advanced forms of technology, and special
      work processes. Nevertheless, unfortunate incidents still occur. To assist
      railway safety management, researchers developed a visual-analytics system. Using
      a data analytics workflow, it compiles an incident risk index that processes
      information about railway incidents. It displays the index on a geographical map,
      together with socioeconomic information about the associated towns and cities.
      Feedback on this system suggests that safety engineers and experts can use it to
      make and communicate decisions. 

PMID- 25073167
TI  - Joint sparse representation of brain activity patterns in multi-task fMRI data.
AB  - A single-task functional magnetic resonance imaging (fMRI) experiment may only
      partially highlight alterations to functional brain networks affected by a
      particular disorder. Multivariate analysis across multiple fMRI tasks may
      increase the sensitivity of fMRI-based diagnosis. Prior research using multi-task
      analysis in fMRI, such as those that use joint independent component analysis
      (jICA), has mainly assumed that brain activity patterns evoked by different tasks
      are independent. This may not be valid in practice. Here, we use sparsity, which
      is a natural characteristic of fMRI data in the spatial domain, and propose a
      joint sparse representation analysis (jSRA) method to identify common information
      across different functional subtraction (contrast) images in data from a multi
      task fMRI experiment. Sparse representation methods do not require independence,
      or that the brain activity patterns be nonoverlapping. We use functional
      subtraction images within the joint sparse representation analysis to generate
      joint activation sources and their corresponding sparse modulation profiles. We
      evaluate the use of sparse representation analysis to capture individual
      differences with simulated fMRI data and with experimental fMRI data. The
      experimental fMRI data was acquired from 16 young (age: 19-26) and 16 older (age:
      57-73) adults obtained from multiple speech comprehension tasks within subjects,
      where an independent measure (namely, age in years) can be used to differentiate
      between groups. Simulation results show that this method yields greater
      sensitivity, precision, and higher Jaccard indexes (which measures similarity and
      diversity of the true and estimated brain activation sources) than does the jICA
      method. Moreover, superiority of the jSRA method in capturing individual
      differences was successfully demonstrated using experimental fMRI data.

PMID- 25073169
TI  - A Geometric Framework for Rectangular Shape Detection.
AB  - Rectangular shape detection has a wide range of applications, such as license
      plate detection, vehicle detection and building detection. In this paper, we
      propose a geometric framework for rectangular shape detection based on the
      channelscale space of RGB images. The framework consists of algorithms developed
      to address three issues of a candidate shape (i.e., a connected component of edge
      points), including: i) outliers, ii) open shape, and iii) fragmentation.
      Furthermore, we propose an interestness measure for rectangular shapes by
      integrating imbalanced points (one type of interest points). Our experimental
      study shows the promise of the proposed framework.

PMID- 25073170
TI  - Enhancing Low-Rank Subspace Clustering by Manifold Regularization.
AB  - Recently, low-rank representation (LRR) method has achieved great success in
      subspace clustering (SC), which aims to cluster the data points that lie in a
      union of low-dimensional subspace. Given a set of data points, LRR seeks the
      lowest rank representation among the many possible linear combinations of the
      bases in a given dictionary or in terms of the data itself. However, LRR only
      considers the global Euclidean structure, while the local manifold structure,
      which is often important for many real applications, is ignored. In this paper,
      to exploit the local manifold structure of the data, a manifold regularization
      characterized by a Laplacian graph has been incorporated into LRR, leading to our
      proposed Laplacian regularized LRR (LapLRR). An efficient optimization procedure,
      which is based on alternating direction method of multipliers (ADMM), is
      developed for LapLRR. Experimental results on synthetic and real data sets are
      presented to demonstrate that the performance of LRR has been enhanced by using
      the manifold regularization.

PMID- 25073168
TI  - Real-time electrical impedance variations in women with and without breast
      cancer.
AB  - The chaotic vascular network surrounding malignant tumors leads to pulsatile
      blood flow patterns that differ from those in benign regions of the breast. This
      study aimed to determine if high-speed electrical impedance tomography (EIT) is
      able to detect conductivity changes associated with cyclic blood-volume changes
      and to gauge the potential of using these signatures to differentiate malignant
      from benign regions within the breast. EIT imaging of pulsating latex membranes
      submerged in saline baths provided initial validation of its use for tracking
      temporally varying conductivities. Nineteen women (10 with cancer, nine without)
      were imaged with EIT over the course of several heartbeats in synchrony with
      pulse-oximetry acquisition. Eight parameters ( rs, phi(rt,max), rt,max,
      Plow:full, Phigh:full, Plow:high) relating the conductivity images and pulse
      oximeter signatures were extracted and used as a means of comparing malignant and
      benign regions of the breast. Significant differences between malignant and
      benign regions of interest were noted in seven of the eight parameters. The
      maximum correlation between conductivity and pulse-oximeter signals, rt,max , was
      observed to be the optimal discriminating parameter with a receiver operating
      characteristic area under the curve of 0.8 and a specificity of 81% at a
      sensitivity of 77%. Assessing the dynamic conductivity of breast may provide
      additional clinical utility to that of standard imaging modalities, but further
      investigation is necessary to better understand the biophysical mechanisms
      leading to the observed conductivity changes.

PMID- 25073171
TI  - Learning-based bipartite graph matching for view-based 3D model retrieval.
AB  - Distance measure between two sets of views is one central task in view-based 3D
      model retrieval. In this paper, we introduce a distance metric learning method
      for bipartite graph matching-based 3D object retrieval framework. In this method,
      the relationship among 3D models is formulated by a graph structure with
      semisupervised learning to estimate the model relevance. More specially, we model
      two sets of views by using a bipartite graph, on which their optimal matching is
      estimated. Then, we learn a refined distance metric by using the user's relevance
      feedback. The proposed method has been evaluated on four data sets and the
      experimental results and comparison with the state-of-the-art methods demonstrate
      the effectiveness of the proposed method.

PMID- 25073172
TI  - Nonlinear deconvolution of hyperspectral data with MCMC for studying the
      kinematics of galaxies.
AB  - Hyperspectral imaging has been an area of active research in image processing and
      analysis for more than 10 years, mainly for remote sensing applications.
      Astronomical ground-based hyperspectral imagers offer new challenges to the
      community, which differ from the previous ones in the nature of the observed
      objects, but also in the quality of the data, with a low signal-to-noise ratio
      and a low resolution, due to the atmospheric turbulence. In this paper, we focus
      on a deconvolution problem specific to hyperspectral astronomical data, to
      improve the study of the kinematics of galaxies. The aim is to estimate the flux,
      the relative velocity, and the velocity dispersion, integrated along the line-of
      sight, for each spatial pixel of an observed galaxy. Thanks to the Doppler
      effect, this is equivalent to estimate the amplitude, center, and width of
      spectral emission lines, in a small spectral range, for every spatial pixel of
      the hyperspectral data. We consider a parametric model for the spectral lines and
      propose to compute the posterior mean estimators, in a Bayesian framework, using
      Monte Carlo Markov chain algorithms. Various estimation schemes are proposed for
      this nonlinear deconvolution problem, taking advantage of the linearity of the
      model with respect to the flux parameters. We differentiate between methods
      taking into account the spatial blurring of the data (deconvolution) or not
      (estimation). The performances of the methods are compared with classical ones,
      on two simulated data sets. It is shown that the proposed deconvolution method
      significantly improves the resolution of the estimated kinematic parameters. 

PMID- 25073173
TI  - Neural Control of a Tracking Task via Attention-Gated Reinforcement Learning for
      Brain-Machine Interfaces.
AB  - Reinforcement learning (RL)-based brain machine interfaces (BMIs) enable the user
      to learn from the environment through interactions to complete the task without
      desired signals, which is promising for clinical applications. Previous studies
      exploited Q-learning techniques to discriminate neural states into simple
      directional actions providing the trial initial timing. However, the movements in
      BMI applications can be quite complicated, and the action timing explicitly shows
      the intention when to move. The rich actions and the corresponding neural states
      form a large state-action space, imposing generalization difficulty on Q
      learning. In this paper, we propose to adopt attention-gated reinforcement
      learning (AGREL) as a new learning scheme for BMIs to adaptively decode high
      dimensional neural activities into seven distinct movements (directional moves,
      holdings and resting) due to the efficient weight-updating. We apply AGREL on
      neural data recorded from M1 of a monkey to directly predict a seven-action set
      in a time sequence to reconstruct the trajectory of a center-out task. Compared
      to Q-learning techniques, AGREL could improve the target acquisition rate to
      90.16% in average with faster convergence and more stability to follow neural
      activity over multiple days, indicating the potential to achieve better online
      decoding performance for more complicated BMI tasks. 

PMID- 25073174
TI  - PEDOT-CNT-Coated Low-Impedance, Ultra-Flexible, and Brain-Conformable Micro-ECoG
      Arrays.
AB  - Electrocorticography (ECoG) is becoming a common tool for clinical applications,
      such as preparing patients for epilepsy surgery or localizing tumor boundaries,
      as it successfully balances invasiveness and information quality. Clinical ECoG
      arrays use millimeter-scale electrodes and centimeter-scale pitch and cannot
      precisely map neural activity. Higher-resolution electrodes are of interest for
      both current clinical applications, providing access to more precise neural
      activity localization and novel applications, such as neural prosthetics, where
      current information density and spatial resolution is insufficient to suitably
      decode signals for a chronic brain-machine interface. Developing such electrodes
      is not trivial because their small contact area increases the electrode
      impedance, which seriously affects the signal-to-noise ratio, and adhering such
      an electrode to the brain surface becomes critical. The most straightforward
      approach requires increasing the array conformability with flexible substrates
      while improving the electrode performance using materials with superior
      electrochemical properties. In this paper, we propose an ultra-flexible and
      conformable polyimide-based micro-ECoG array of submillimeter recording sites
      electrochemically coated with high surface area conductive polymer-carbon
      nanotube composites to improve their brain-electrical coupling capabilities. We
      characterized our devices both electrochemically and by recording from rat
      somatosensory cortex in vivo. The performance of the coated and uncoated
      electrodes was directly compared by simultaneously recording the same neuronal
      activity during multiwhisker deflection stimulation. Finally, we assessed the
      effect of electrode size on the extraction of somatosensory evoked potentials and
      found that in contrast to the normal high-impedance microelectrodes, the
      recording capabilities of our low-impedance microelectrodes improved upon
      reducing their size from 0.2 to 0.1 mm. 

PMID- 25073175
TI  - A vestibular prosthesis with highly-isolated parallel multichannel stimulation.
AB  - This paper presents an implantable vestibular stimulation system capable of
      providing high flexibility independent parallel stimulation to the semicircular
      canals in the inner ear for restoring three-dimensional sensation of head
      movements. To minimize channel interaction during parallel stimulation, the
      system is implemented with a power isolation method for crosstalk reduction.
      Experimental results demonstrate that, with this method, electrodes for different
      stimulation channels located in close proximity ( mm) can deliver current pulses
      simultaneously with minimum inter-channel crosstalk. The design features a memory
      based scheme that manages stimulation to the three canals in parallel. A
      vestibular evoked potential (VEP) recording unit is included for closed-loop
      adaptive stimulation control. The main components of the prototype vestibular
      prosthesis are three ASICs, all implemented in a 0.6- MUm high-voltage CMOS
      technology. The measured performance was verified using vestibular electrodes in
      vitro. 

PMID- 25073176
TI  - On recursive edit distance kernels with application to time series
      classification.
AB  - This paper proposes some extensions to the work on kernels dedicated to string or
      time series global alignment based on the aggregation of scores obtained by local
      alignments. The extensions that we propose allow us to construct, from classical
      recursive definition of elastic distances, recursive edit distance (or time-warp)
      kernels that are positive definite if some sufficient conditions are satisfied.
      The sufficient conditions we end up with are original and weaker than those
      proposed in earlier works, although a recursive regularizing term is required to
      get proof of the positive definiteness as a direct consequence of the Haussler's
      convolution theorem. Furthermore, the positive definiteness is maintained when a
      symmetric corridor is used to reduce the search space, and thus the algorithmic
      complexity, which is quadratic in the worst case. The classification experiment
      we conducted on three classical time-warp distances (two of which are metrics),
      using support vector machine classifier, leads to the conclusion that when the
      pairwise distance matrix obtained from the training data is far from
      definiteness, the positive definite recursive elastic kernels outperform in
      general the distance substituting kernels for several classical elastic distances
      we have tested. 

PMID- 25073177
TI  - Generalized multiple kernel learning with data-dependent priors.
AB  - Multiple kernel learning (MKL) and classifier ensemble are two mainstream methods
      for solving learning problems in which some sets of features/views are more
      informative than others, or the features/views within a given set are
      inconsistent. In this paper, we first present a novel probabilistic
      interpretation of MKL such that maximum entropy discrimination with a
      noninformative prior over multiple views is equivalent to the formulation of MKL.
      Instead of using the noninformative prior, we introduce a novel data-dependent
      prior based on an ensemble of kernel predictors, which enhances the prediction
      performance of MKL by leveraging the merits of the classifier ensemble. With the
      proposed probabilistic framework of MKL, we propose a hierarchical Bayesian model
      to learn the proposed data-dependent prior and classification model
      simultaneously. The resultant problem is convex and other information (e.g.,
      instances with either missing views or missing labels) can be seamlessly
      incorporated into the data-dependent priors. Furthermore, a variety of existing
      MKL models can be recovered under the proposed MKL framework and can be readily
      extended to incorporate these priors. Extensive experiments demonstrate the
      benefits of our proposed framework in supervised and semisupervised settings, as
      well as in tasks with partial correspondence among multiple views. 

PMID- 25073178
TI  - A CADx scheme for mammography empowered with topological information from
      clustered microcalcifications' atlases.
AB  - A computer-aided diagnosis (CADx ) framework for the diagnosis of clustered
      microcalcifications (MCs) has already been developed, which is based on the
      analysis of MCs' morphologies,the shape of the cluster they form and the texture
      of the surrounding tissue. In this study, we investigate the diagnostic
      information that the relative location of the cluster inside the breast may
      provide. Breast probabilistic maps are generated and adopted in the CADx
      pipeline, expecting to empower its diagnostic procedure. We propose a flowchart
      combining alternative classification algorithms and the aforementioned
      probabilistic maps in order to provide a final risk for malignancy for new
      considered mammograms. For the evaluation performance, a large dataset of
      mammograms provided from the Digital Database of Screening Mammography (DDSM) has
      been used. The obtained results indicate that the proposed modifications lead to
      the enhancement of the diagnostic process, as the classification results are
      further improved. Additionally, a straightforward comparison between the CADx
      pipeline and the radiologists who assessed the same mammograms, reveal that the
      CADx pipeline performs toward the right direction, as the sensitivity remains at
      high levels, while improving both the accuracy, from 51.4% to 69%, and the
      specificity, from 16.6% to 54.7%.

PMID- 25073179
TI  - Improving dermoscopy image classification using color constancy.
AB  - Robustness is one of the most important characteristics of computer-aided
      diagnosis systems designed for dermoscopy images. However, it is difficult to
      ensure this characteristic if the systems operate with multisource images
      acquired under different setups. Changes in the illumination and acquisition
      devices alter the color of images and often reduce the performance of the
      systems. Thus, it is important to normalize the colors of dermoscopy images
      before training and testing any system. In this paper, we investigate four color
      constancy algorithms: Gray World, max-RGB, Shades of Gray, and General Gray
      World. Our results show that color constancy improves the classification of
      multisource images, increasing the sensitivity of a bag-of-features system from
      71.0% to 79.7% and the specificity from 55.2% to 76% using only 1-D RGB
      histograms as features. 

PMID- 25073180
TI  - A decision-support framework for promoting independent living and ageing well.
AB  - Artificial intelligence and decision support systems offer a plethora of health
      monitoring capabilities in ambient assisted living environment. Continuous
      assessment of health indicators for elderly people living on their own is of
      utmost importance, so as to prolong their independence and quality of life. Slow
      varying, long-term deteriorating health trends are not easily identifiable in
      seniors. Thus, early sign detection of a specific condition, as well as, any
      likely transition from a healthy state to a pathological one are key problems
      that the herein proposed framework aims at resolving. Statistical process control
      concepts offer a personalized approach toward identification of trends that are
      away from the atypical behavior or state of the seniors, while fuzzy cognitive
      maps knowledge representation and inference schema have proved to be efficient in
      terms of disease classification. Geriatric depression is used as a case study
      throughout the paper, so to prove the validity of the framework, which is planned
      to be pilot tested with a series of lone-living seniors in their own homes.

PMID- 25073182
TI  - Ordinal regression by a generalized force-based model.
AB  - This paper introduces a new instance-based algorithm for multiclass
      classification problems where the classes have a natural order. The proposed
      algorithm extends the state-of-the-art gravitational models by generalizing the
      scaling behavior of the class-pattern interaction force. Like the other
      gravitational models, the proposed algorithm classifies new patterns by comparing
      the magnitude of the force that each class exerts on a given pattern. To address
      ordinal problems, the algorithm assumes that, given a pattern, the forces
      associated to each class follow a unimodal distribution. For this reason, a
      weight matrix that allows to modify the metric in the attributes space and a
      vector of parameters that allows to modify the force law for each class have been
      introduced in the model definition. Furthermore, a probabilistic formulation of
      the error function allows the estimation of the model parameters using global and
      local optimization procedures toward minimization of the errors and penalization
      of the non unimodal outputs. One of the strengths of the model is its competitive
      grade of interpretability which is a requisite in most of real applications. The
      proposed algorithm is compared to other well-known ordinal regression algorithms
      on discretized regression datasets and real ordinal regression datasets.
      Experimental results demonstrate that the proposed algorithm can achieve
      competitive generalization performance and it is validated using nonparametric
      statistical tests. 

PMID- 25073181
TI  - Smartphone-based recognition of states and state changes in bipolar disorder
      patients.
AB  - Today's health care is difficult to imagine without the possibility to
      objectively measure various physiological parameters related to patients'
      symptoms (from temperature through blood pressure to complex tomographic
      procedures). Psychiatric care remains a notable exception that heavily relies on
      patient interviews and self-assessment. This is due to the fact that mental
      illnesses manifest themselves mainly in the way patients behave throughout their
      daily life and, until recently there were no "behavior measurement devices." This
      is now changing with the progress in wearable activity recognition and sensor
      enabled smartphones. In this paper, we introduce a system, which, based on
      smartphone-sensing is able to recognize depressive and manic states and detect
      state changes of patients suffering from bipolar disorder. Drawing upon a real
      life dataset of ten patients, recorded over a time period of 12 weeks (in total
      over 800 days of data tracing 17 state changes) by four different sensing
      modalities, we could extract features corresponding to all disease-relevant
      aspects in behavior. Using these features, we gain recognition accuracies of 76%
      by fusing all sensor modalities and state change detection precision and recall
      of over 97%. This paper furthermore outlines the applicability of this system in
      the physician-patient relations in order to facilitate the life and treatment of
      bipolar patients.

PMID- 25073183
TI  - Adaptive distributed outlier detection for WSNs.
AB  - The paradigm of pervasive computing is gaining more and more attention nowadays,
      thanks to the possibility of obtaining precise and continuous monitoring. Ease of
      deployment and adaptivity are typically implemented by adopting autonomous and
      cooperative sensory devices; however, for such systems to be of any practical
      use, reliability and fault tolerance must be guaranteed, for instance by
      detecting corrupted readings amidst the huge amount of gathered sensory data.
      This paper proposes an adaptive distributed Bayesian approach for detecting
      outliers in data collected by a wireless sensor network; our algorithm aims at
      optimizing classification accuracy, time complexity and communication complexity,
      and also considering externally imposed constraints on such conflicting goals.
      The performed experimental evaluation showed that our approach is able to improve
      the considered metrics for latency and energy consumption, with limited impact on
      classification accuracy. 

PMID- 25073185
TI  - 5 steps to adapt your home as you age. Modifying doorknobs, doorways, and
      railings now will help you live there longer.

PMID- 25073184
TI  - Early-life bisphenol a exposure and child body mass index: a prospective cohort
      study.
AB  - BACKGROUND: Early-life exposure to bisphenol A (BPA) may increase childhood
      obesity risk, but few prospective epidemiological studies have investigated this
      relationship. OBJECTIVE: We sought to determine whether early-life exposure to
      BPA was associated with increased body mass index (BMI) at 2-5 years of age in
      297 mother-child pairs from Cincinnati, Ohio (HOME Study). METHODS: Urinary BPA
      concentrations were measured in samples collected from pregnant women during the
      second and third trimesters and their children at 1 and 2 years of age. BMI z
      scores were calculated from weight/height measures conducted annually from 2
      through 5 years of age. We used linear mixed models to estimate BMI differences
      or trajectories with increasing creatinine-normalized BPA concentrations.
      RESULTS: After confounder adjustment, each 10-fold increase in prenatal (beta = 
      0.1; 95% CI: -0.5, 0.3) or early-childhood (beta = -0.2; 95% CI: -0.6, 0.1) BPA
      concentrations was associated with a modest and nonsignificant reduction in child
      BMI. These inverse associations were suggestively stronger in girls than in boys
      [prenatal effect measure modification (EMM) p-value = 0.30, early-childhood EMM p
      value = 0.05], but sex-specific associations were imprecise. Children in the
      highest early-childhood BPA tercile had lower BMI at 2 years (difference = -0.3;
      95% CI: -0.6, 0.0) and larger increases in their BMI slope from 2 through 5 years
      (BMI increase per year = 0.12; 95% CI: 0.07, 0.18) than children in the lowest
      tercile (BMI increase per year = 0.07; 95% CI: 0.01, 0.13). All associations were
      attenuated without creatinine normalization. CONCLUSIONS: Prenatal and early
      childhood BPA exposures were not associated with increased BMI at 2-5 years of
      age, but higher early-childhood BPA exposures were associated with accelerated
      growth during this period.

PMID- 25073186
TI  - Ask the doctor.  Why am I shrinking as I'm getting older, and is there anything I
      can do about it?

PMID- 25073187
TI  - Ask the doctor.  Is it true that snoring raises your blood pressure?  I'm a
      snorer, and I worry that it puts me at risk for other conditions.

PMID- 25073188
TI  - Boost your thinking skills with exercise.  Moderate-intensity exercise can help
      improve your thinking and memory in just six months.

PMID- 25073189
TI  - Relief dos and don'ts for that nagging neck pain.  Adjusting your position and
      posture can help.

PMID- 25073190
TI  - Caffeine IQ: how much is too much?  Most people can drink a few cups a day.  A
      higher intake may have negative side effects.

PMID- 25073191
TI  - Are you losing your sense of smell? An evaluation can indicate whether it's due
      to aging, blockage, or a neurological condition.

PMID- 25073192
TI  - Fast way to improve heart and muscle fitness.  Stair climbing burns twice the
      calories of walking, and it strengthens your heart, lungs, and muscles.

PMID- 25073193
TI  - Erectile dysfunction and the drugs to treat it.  In many cases, medications are
      all a man needs to stay sexually active.

PMID- 25073194
TI  - More benefits of eating a vegetarian diet.

PMID- 25073195
TI  - Mind your own health after the death of a partner.

PMID- 25073196
TI  - Blood pressure drugs associated with fall risk.

PMID- 25073197
TI  - [Contribution of rapid diagnostic test in the treatment of infectious diseases].
AB  - According to aging of population and medical progress, the risk and mortality
      rate of pneumonia have been increased. In the causative organism inspection,
      smear-culture examination of sputum is the gold standard. When it is difficult to
      obtain high quality sputum and to culture the causative organism, or when
      antibiotics are previously administered, we have no choice but to start the
      treatment with pathogenic bacteria unknown. In these cases, it is necessary to
      select an appropriate test method for expecting pathogen. If bacteria are
      detected in laboratory culture, it is difficult to distinguish whether it is a
      causative or colonizers. Future development is expected in rapid diagnostic
      methods.

PMID- 25073198
TI  - [Rapid diagnosis and viral infections topics, interpretation of the results and
      characteristics of the virus-detection].

PMID- 25073199
TI  - [Evaluation of the sensitivity of a densitometry system, in judging the result of
      influenza virus antigen-detection kit using immunochromatography].
AB  - Immunochromatography viral antigen-detection kits have become popular in clinical
      settings in Japan. Influenza virus detection kit is one of them. It is sometimes
      used in early phase of the disease, combined with the early treatment with anti
      influenza drugs. Most of them are invented to visually read the test line on
      their kits. However, we should be careful about their reliability of them.
      Sometimes human errors occur at the visual tests, and they have different
      sensitivities among the kits from different companies. In this report, we
      evaluated the sensitivity of BD Veritor System Flu with its reader by comparing
      with conventional visual tests. A total of 84 people including laboratory
      technologists were asked to visually read test line and their answers were
      compared with results of BD Veritor System Reader. This study showed that the
      lower the concentration of standard sample was applied, the greater the error
      ratio of visual test became, indicating the stable sensitivity of Veritor System.
      Moreover, the sensitivity was compared with three other major products approved
      in Japan, using four influenza viruses: type A of H1N1 seasonal 2009, H1N1
      pandemic 2009, H3N2 seasonal 2012 and type B of seasonal 2012. It was indicated
      that Veritor System had the highest limit of detection from the kits.

PMID- 25073200
TI  - Acute medicine. Editorial.

PMID- 25073201
TI  - Picture quiz: A life-threatening cause of abdominal pain. Diagnosis: Aortic
      aneurysm.

PMID- 25073202
TI  - British Society of Echocardiography adult accreditation: an unrealistic
      expectation for acute physicians?

PMID- 25073203
TI  - [Proceeding of branch meetings for the Japanese society for history of pharmacy,
      2014].

PMID- 25073204
TI  - Writing an effective introduction for a scientific manuscript.

PMID- 25073205
TI  - 20 years of arterial switch operation for simple TGA.
AB  - BACKGROUND: Arterial switch operation became the golden treatment for simple
      transposition of the great arteries (sTGA). We describe our experience with the
      arterial switch operation regarding long-term outcome and the need for re
      intervention. Nevertheless, supravalvular pulmonary stenosis (SPS) remains a
      concern in the long run. We assess the evolution of SPS over time and evaluate
      the effect of technical modifications on SPS during our experience. METHODS: We
      performed a retrospective study on 133 patients operated with ASO for TGA between
      October 1991 and November 2009. Last report method was used. We reviewed our
      pediatric cardiology and cardiac surgery database to examine the
      echocardiographic data and electrocardiograms. A mean follow-up of 9.2 years (+/-
      5.83 SD) was reached. RESULTS: One (0.8%) patient deceased postoperatively due to
      cardiogenic shock. The overall actuarial freedom from reoperation (open and
      percutaneous) was 88.1%, 78.5% and 76.9% at 1, 5 and 10 years. SPS needed to be
      treated in 17 patients. Valve regurgitation at final investigation was maximal
      moderate in 5 patients for the aortic valve, 10 for pulmonary valve and 3 in
      tricuspid valve. CONCLUSIONS: ASO shows excellent long-term results in sTGA with
      a very low morbidity and mortality and is therefore the procedure of choice. Re
      intervention rate is determined by SPS. Since the extensive mobilization of the
      pulmonary arteries and the creation of a longer neo-pulmonary root, reduction in
      SPS was seen with no re-interventions in the second half of the group. To obtain
      a final comparison with the atrial switch operation, a longer Follow-up is
      necessary.

PMID- 25073206
TI  - Mid-term follow-up after maze IV procedures for concomitant atrial fibrillation.
AB  - BACKGROUND: We performed a retrospective analysis of the maze IV procedures
      performed in our surgical department for concomitant atrial fibrillation.
      METHODS: Preoperative, in-hospital and postoperative follow-up data were
      collected from 46 consecutive patients who underwent the maze IV operation
      between April 2006 and December 2010. All electrocardiograms and Holters were
      reviewed. RESULTS: One patient died in-hospital. During a mean follow-up of 25 +/
      16.3 months seven patients died: two related to a hemorrhagic stroke, one due to
      right ventricular failure, the remainder deaths were not cardiac related. The
      success rate, defined as no recurrence of AF or atrial flutter with a blanking
      period of 6 months postoperatively, was 73.7%. Plots of probability of freedom of
      atrial fibrillation over time are drawn and reach a stable level after one year.
      CONCLUSIONS: The mid term results of the maze IV procedures for concomitant
      atrial fibrillation are very good. The results are stable for the remainder of
      follow-up.

PMID- 25073207
TI  - Estimated incidence of cardiac contusion using transthoracic echocardiography in
      patients suffering from severe blunt trauma to the chest.
AB  - BACKGROUND: Cardiac contusion (CC) is a known complication of blunt trauma to the
      chest. There have been debates about its true incidence and there are different
      reports which claim that it occurs in less than 10% to more than 70% of patients.
      The goal of this study is to estimate the incidence of CC in patients with severe
      blunt chest trauma (SBCT) using transthoracic echocardiography (TTE). METHODS:
      After defining inclusion and exclusion criteria, all cases with clinical
      evidences of SBCT from February 2010 until October 2011 were included in this
      study. Patients were assessed using electrocardiography (ECG) and transthoracic
      echocardiography (TTE). Transient echocardiographic changes, including wall
      motion abnormalities, valvular or papillary muscle dysfunction, pericardial
      effusion or tamponade, free wall rupture and interatrial/interventricular septum
      defects, were considered to be abnormal and trauma-related. RESULTS: A total of
      210 patients were assessed for CC. Fifty-two trauma-related echocardiographic
      changes in 47 patients were observed, in which 34 cases had simultaneous
      transient ECG changes. The estimated incidence of CC in these subjects was
      calculated to be 23.38% and 16.19%, respectively. There was a statistically
      significant relationship between the presence of both echocardiographic changes
      and ECG abnormalities, and those subjects without ECG changes (P = 0.03). As we
      evaluated stable patients without any cardiac-related clinical manifestations and
      TTE was chosen as our diagnostic modality, we claim that the true incidence must
      be higher. CONCLUSIONS: We believe that a comparison of our findings with those
      presented in the literature shows that the actual incidence of CC in blunt chest
      trauma is underestimated.

PMID- 25073208
TI  - Solid pseudopapillary tumor of the pancreas: a report of six cases.
AB  - BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare
      pancreatic neoplasm. The aim of this study was to discuss the clinical
      presentation, management, and outcome of patients with this kind of tumor.
      MATERIALS AND METHODS: A retrospective review was performed in 6 patients with
      SPTP surgically treated between January 2004 and September 2011 in our hospital.
      RESULTS: All the 6 patients were female. The mean age of the patients was 39
      years (range, 18 to 67 years). The main clinical presentation was abdominal pain
      or discomfort, however a third of the patients were asymptomatic. The mean size
      of the tumor was 9.7 cm (range, 2.5 to 18 cm). Three tumors had a well defined
      capsule, 3 tumors extended in the pancreas. Four of the 6 tumors had a cystic
      component, and calcifications were observed in one tumor. No lymph node
      involvement, no lymphatic invasion and no nerve invasion were observed. One tumor
      showed an infiltration of the splenic vein, and another patient had a liver
      metastasis with complete resection. Distal pancreatectomy (n = 3), local
      resection (n = 1), cephalic duodenopancreatectomy (n = 1), and distal
      pancreatectomy associated with a right hepatectomy (n = 1) were performed. The
      main postoperative complication in the short-term was bleeding (n = 1), and long
      term the development of an insulin-requiring diabetes (n = 2). No patient
      received adjuvant therapy. Overall mortality rate was 0%. All patients were still
      alive without recurrent disease with a median follow up of 36.2 months.
      CONCLUSION: Patients with SPTP have an excellent prognosis after its complete
      removal, even if it is a minimized resection.

PMID- 25073209
TI  - Is FNAC (fine needle aspiration cytology) a useful tool in detection of
      malignancy in thyroid surgery? A single institution experience.
AB  - OBJECTIVE: To evaluate if FNAC (Fine Needle Aspiration Cytology) is a useful tool
      in the detection of malignancy in thyroid surgery. FNAC is used routinely as a
      preoperative diagnostic technique and surgical strategy is often adapted. But is
      FNAC such a good technique in defining surgical strategy? METHODS: We
      retrospectively reviewed all files of 703 patients operated from 1997 till today.
      We obtained the results of the FNAC, the final pathological diagnosis and these
      data were analyzed. RESULTS: There were 161 male and 542 female patients. 72 out
      703 patients had a malignancy. 241 patients (34.3%) had a preoperative FNAC
      procedure. Male patients had significantly more malignancies (p = 0.006). In 183
      patients (75.9%) the FNAC was benign, 28 patients (11.6%) showed malignancy, in
      15 patients (6.2%) only blood was found and 15 patients (6.2%) showed an
      inconclusive result. 70.1% of the patients were true negative, 5.8% were true
      positive, 5.8% false positive, 5.8% false negatives, 5.8% of inconclusive results
      were malignant on pathology. This gives a sensitivity of 50% and specificity of
      92.4%. CONCLUSIONS: The specificity of FNAC in malignancy is high (92.4%) but a
      sensitivity of 50% is low. With these results adaptation of surgical strategy
      (hemithyroidectomy or total thyroidectomy) secondary to the results of the FNAC
      is not recommended. Free hand FNAC might be a reason for the relatively high
      percentage of inconclusive results. Ultrasound guided FNAC can improve the yield
      of the puncture. On top of that pathological interpretation of the cytology is
      not always straight forward.

PMID- 25073210
TI  - Parathyroidectomy in primary hyperparathyroidism: retrospective study of 167
      patients, experience in Jules Bordet Institute.
AB  - The aim of this study is to compare our surgical results of parathyroidectomies
      in primary hyperparathyroidism with literature results. From 1985 until 2009, 167
      patients were operated for primary hyperparathyroidism by bilateral central neck
      exploration. The sex ratio (women/men) is 4/1 and the middle age is 57 years old.
      We record clinical information, laboratory and radiological results of the
      preoperative period. We count 158 adenomas, 5 parathyroid hyperplasias, two
      carcinomas and two parathyroid glands reported as normal. The morbidity rate was
      low (0.6%) and there was no mortality. With a mean follow-up of 6 years, the
      majority of symptoms and clinical signs improved after surgery, the parathyroid
      hormone level (PTH) and the calcaemia normalized in all patients except 4/166
      (2.41%). Among twenty-four patients who go for a Dual-Energy X-ray Absorptiometry
      test (DEXA), 16/24 (66.67%) demonstrated a lumbar spine bone mass increase and
      15/24 (62.5%) a total hip bone mass increase. There was one recurrence of
      hyperparathyroidism due to a missed second adenoma in the mediastinum. In
      conclusion, the parathyroidectomy by bilateral neck exploration under general
      anesthesia in the treatment of primary hyperparathyroidism is a surgical
      technique associated with a high recovery rate and a low complications rate. A
      systematic study of the bone mass before and after parathyroidectomy should allow
      identification of the factors that are associated with the bone density increase
      of these patients.

PMID- 25073211
TI  - Feasibility and effectiveness of primary umbilical hernia repair with biologic
      graft: preliminary study.
AB  - BACKGROUND: In this prospective non-randomized observational cohort study we
      evaluated: the feasibility and effectiveness of primary umbilical hernia repair
      with open tension-free and sutureless technique using a porcine small intestinal
      submucosa (Surgisis) prosthesis, the quality of the treatment in terms of
      reduction of postoperative discomfort and the complications at early and long
      term follow-up. METHODS: Thirty-six consecutive patients, mean age 45.25 +/-
      12.19 years, affected by primary umbilical uncomplicated hernia with a defect
      size < or = 3 cm, were treated in a day-surgery setting. A tailored flat Surgisis
      graft was used to ensure an overlap of at least 2 cm; in all patients the mesh
      was fixed by fibrin glue. Collected data included: visual analogic scale (VAS)
      pain scores at 24 hours, 72 hours, and 7, 15, and 30 days and number of analgesic
      medications after operation, complications rate, the quality of life measured by
      Short Form 36 health survey questionnaire (SF-36) before the operation and at
      long term follow-up. RESULTS: The mean follow-up time was 5.6 +/- 1.4 years.
      Postoperative pain was low: the mean visual analogic scale (VAS) scores were 2.8
      at 24 h, 1.8 at 72 h, and 0.9, 0.3, and 0.04 at 7, 15, and 30 days, respectively.
      77.8% of the patients (28/36) did not use any analgesic drugs. Seroma was
      reported in 13.8% of the patients (5/36); there were no hematomas, infection,
      chronic pain and no major complications or mortality (< or = 30 days). Recurrence
      rate was 2.8% (1/36). Patient satisfaction showed a significant improvement in
      all SF-36 domain scores (P < 0.001). CONCLUSIONS: The biologic mesh seems to be a
      safe and reliable device for repairing primary umbilical hernia with high patient
      comfort, even if not yet an alternative to synthetic mesh.

PMID- 25073212
TI  - Morgagni hernia: transabdominal or transthoracic approach?
AB  - BACKGROUND: Morgagni hernias are rare and constitute less than 2% of all
      diaphragmatic hernias. Treatment is primarily surgical and transthoracic or
      transabdominal route approach methods are amenable. In this study, we compared
      the results of our Morgagni hernia cases, which underwent either transabdominal
      or transthoracic method of surgery. METHODS: We retrospectively analyzed the
      records of 20 patients we operated on for Morgagni hernias between 1997 and 2011
      in our clinic. Age, sex, presenting symptoms, lesion location, diagnoses, applied
      surgical method, duration of the hospital stay, morbidity and mortality rates
      were reviewed. Six of the cases were (30%) approached via thoracotomy and 14
      (70%) were laparotomy. The hernial sac was resected in all cases. Diaphragmatic
      defects were repaired using nonabsorbable sutures in all cases except in one case
      where prolen mesh used. RESULTS: Thirteen cases (65%) were female and seven (35%)
      were male. Mean age was 44.1 +/- 25.3 years (1-73 years). Hernias were located on
      the right side in 18 cases, the left side in one, and bilaterally located in one
      case. Herniated organs were: omentum in 19 (95%), transverse colon in 18 (90%),
      small bowel in 4 (20%), stomach in 3 (15%), and left lobe of the liver in one
      (5%) case. No complication was observed in patients who underwent laparotomy, and
      wound infection occurred in one patient who underwent thoracotomy. Hospital stays
      in thoracotomy and laparotomy groups are 7 and 6.2 days, respectively. There were
      no mortalities observed. There was no recurrence during the follow-up of 36.4
      months (10-116 months). CONCLUSION: Our findings showed that both surgical
      methods have similar and satisfactory results. Although transthoracic approach
      was preferred in previous cases, the transabdominal approach was preferred in
      later ones because we assumed that the later procedure is less invasive for the
      patient. We prefer and propose the abdominal approach for the surgical management
      of Morgagni hernias.

PMID- 25073213
TI  - Abdominal aortic aneurysm rupture into a retro-aortic left renal vein.
AB  - We present a case of an abdominal aortic aneurysm ruptured into a retroaortic
      left renal vein. The patient presented with left flank pain, left-sided
      varicocoele and haematuria. Imaging showed a juxtarenal AAA associated with a
      retroaortic left renal vein and simultaneous contrast captation of the aneurysm,
      the vena cava, the left renal vein and the left vena testicularis. After opening
      of the aneurysm sac, the defect was controlled by digital pressure and closed by
      suture. The patient underwent a successful abdominal aorto bi-iliac replacement.
      We discuss prevalence, clinical features and treatment options of this rare
      condition.

PMID- 25073214
TI  - Hepatic angiomyolipoma: what management?
AB  - An 80-year-old woman was referred for the surgical treatment of a 110-mm right
      hepatic tumor. The biopsy revealed an adenoma, and a right hepatectomy was
      performed. Histopathology indicated a major fat component with epitheliod cells,
      immunoreactivity for HMB45, Melan A, and smooth muscle actin, describing a
      hepatic epithelioid angiomyolipoma (AML). The AML belongs to the group of tumors
      with a Perivascular Epithelioid Cell differentiation. Its diagnosis is based on
      imaging and biopsy, and therefore might be difficult. Hepatic AML are mainly
      benign tumors; however, some tend to behave in a malignant manner. In case of
      histological proof, close clinical and radiological monitoring can be proposed if
      its size is less than 5 cm and no pejorative histological features are found.
      Nevertheless, follow-up is still required if resection is performed in search of
      recurrence or metastatic spread.

PMID- 25073215
TI  - Primitive pulmonary "malignant epithelioid hemangioendothelioma" versus
      epithelioid angiosarcoma. A case report and review of the literature.
AB  - We describe the case of a 56-year-old man presenting a primary pulmonary
      epithelioid angiosarcoma versus malignant epithelioid hemangioendothelioma still
      alive, without recurrence at nearly two years after the beginning of the
      symptoms. The primary pulmonary angiosarcoma is extremely rare, being reported
      only in a handful of cases. Metastatic involvement of the lung (90%) is far more
      common than primary pulmonary involvement (10%). Various predisposing condition
      for the development of angiosarcoma have been described. Early diagnosis is not
      common, because of the rarity of angiosarcoma in the lung and consequent low
      index of suspicion. Due to the paucity of cases, there are no defined treatment
      regimens for this entity. However, there is a tendency for surgical intervention
      in all reported cases.

PMID- 25073216
TI  - Vulvar defect after pelvic trauma and its repair with reverse TRAM flap: report
      of a case.
AB  - Vulvar defect and soft tissue loss secondary to pelvic trauma is rare. Many
      reconstructive procedures for large vulvoperineal defects have been described.
      The case of a woman with severe vulvar defect following a previous pelvic trauma
      and treatment with reverse TRAM flap is reported.

PMID- 25073217
TI  - De Garengeot's hernia: acute appendicitis in a femoral hernia. Case report and
      literature overview.
AB  - Migration of the appendix vermiformis into a femoral hernia is also known as De
      Garengeot's hernia. We report the case of an elderly patient who was diagnosed
      with an acute appendicitis within a strangulated femoral hernia sac. Emergency
      incision and abscess drainage was performed, followed by delayed laparoscopic
      appendectomy and herniorraphy. Both procedures were uneventful and the patient
      fully recovered. Although exceedingly rare, the surgeon needs to be aware of this
      entity to prevent a delay in diagnosis with potentially serious adverse events.

PMID- 25073218
TI  - Sugar, what are we advising our patients?

PMID- 25073219
TI  - 'The last post?': assessment of the failing post-retained crown.
AB  - Failure of a post-retained restoration can provide a challenge to the general
      dental practitioner (GDP) in terms of diagnosis, treatment planning and
      communication with the patient. The cause of failure must be identified, and a
      thorough assessment of the restoration, remaining tooth and its functional and
      aesthetic demands carried out in order to plan treatment to provide the most
      reliable result. Clinical Relevance: This article discusses the assessment of
      failing post-retained crowns, with discussion of reasons for failure, thereby
      assisting the GDP in decision-making and treatment planning for such teeth.

PMID- 25073220
TI  - Haemostasis. Part 2: Medications that affect haemostasis.
AB  - Post-operative haemorrhage is a recognized complication in dental practice. This
      may be more prevalent in patients taking antithrombotic medications. It is
      important that the dentist understands the mechanism of action of these drugs and
      how they may affect management of dental patients. Clinical Relevance: Dental
      professionals must be aware of those medications affecting haemostasis and how
      they may impact on management. The emergence of different therapeutic regimens
      has increased the number of such drugs.

PMID- 25073221
TI  - Minimal intervention dentistry and older patients. Part 1: Risk assessment and
      caries prevention.
AB  - Ten million people in the UK today are aged over 65. The latest projections
      estimate that there will be 5 1/2 million more people aged 65 and older in the
      next 20 years. This projected pattern of population ageing will have profound
      consequences for dentistry. Minimal intervention dentistry (MID) is a modern
      evidence-based approach to caries management in dentate patients that uses the
      'medical model' whereby disease is controlled by the 'oral physician'. This
      approach offers considerable benefits over conventional dentistry for older
      patients. It encourages patients to be responsible for their oral health through
      the provision of both knowledge and motivation. MID encompasses risk assessment
      for dental disease, early detection and control of disease processes, and
      minimally invasive treatment. Clinical Relevance: Risk assessment tools can aid
      the general dental practitioner and the patient to develop a suitable caries
      prevention programme for that individual and reduce the need for future operative
      intervention.

PMID- 25073222
TI  - Dysphagia and dentistry.
AB  - Dysphagia is defined as a 'difficulty in swallowing' and is commonly found in the
      general population, particularly in the elderly. This article gives an overview
      of the more frequently encountered swallowing disorders and provides advice on
      how to manage the dysphagic patient in the dental surgery. Clinical Relevance: By
      identifying patients with dysphagia and being aware of the potential problems
      that the clinician may experience when treating them, the risk of aspiration,
      choking and healthcare-acquired upper respiratory tract infections may be
      reduced.

PMID- 25073223
TI  - The management of risk. Part 4: Resolving complaints.
AB  - Patient complaints invariably cause concern and distress. Whilst prevention
      should be the primary objective, this is not always possible. This final article
      in the series describes strategies for the management and resolution of
      complaints, as well as the advantages of good complaint handling. Clinical
      Relevance: Early and efficient resolution of complaints will reduce stress to all
      members of the dental team.

PMID- 25073224
TI  - Bilateral balanced articulation: science or dogma?
AB  - For more than a hundred years, it has been supposed that canine guidance should
      be avoided in conventional complete dentures, since it would result in denture
      instability. Thus, bilateral balanced articulation has been held by many authors
      as fundamental for treatment success. However, randomized clinical trials have
      shown that balanced articulation is not as important as previously thought. The
      issue about which occlusal concept is the most appropriate for individual needs
      is clinically and economically relevant for both the dentist and dental
      technician. Therefore, the purpose of this study is to provide an evidence-based
      update on complete denture occlusion. Clinical Relevance: The issue about which
      occlusal concept is the most appropriate for individual needs is clinically and
      economically relevant.

PMID- 25073225
TI  - Evaluation of a novel compule-based gingival retraction system in UK general
      dental practices.
AB  - Twelve members were selected at random from the PREP panel, a group of UK-based
      dentists who are prepared to carry out research in their practices. A
      questionnaire was designed to determine the views of the participants, who were
      asked to use the retraction paste capsules where clinically indicated. They were
      asked to return the questionnaire after 8 weeks and the information contained
      therein was collated and presented mainly on visual analogue scales (VAS). A
      total of 160 impressions were taken using the Astringent Retraction Paste (3M
      ESPE, Seefeld, Germany) plus use in the placement of 25 restorations. Of
      evaluators, 83% (n = 10) agreed that Astringent Retraction Paste was a suitable
      product for gingival retraction and 75% (n = 9) agreed that it had good
      haemostatic properties. Overall dispensing and handling of the paste was rated as
      4.9 on a VAS scale where 1 = Inconvenient and 5 = Convenient. The viscosity of
      the paste was rated as 3.6 on a VAS where 1 = too thin and 5 = too thick. Good
      scores were achieved across all criteria for the product. Clinical Relevance:
      Practitioners may wish to be aware of a novel compule-based gingival retraction
      system.

PMID- 25073226
TI  - Medication-related tooth discoloration: a review.
AB  - Tooth discoloration is a common problem for which patients seek dental care.
      Various medications can directly or indirectly result in tooth discoloration. As
      clinicians, it is our responsibility to know these therapeutic drugs which can
      cause tooth discoloration and educate our fellow colleagues to take necessary
      precautions when prescribing these medications. Therefore, the objective of this
      paper is to give an overview of the various medications that can be linked to
      tooth discoloration and to suggest the precautionary measures that can be taken
      to avoid or minimize it. Clinical Relevance: Dental discoloration potential of
      medications always needs to be considered before prescribing them.

PMID- 25073227
TI  - Denosumab-associated osteonecrosis of the jaw--a case report.
AB  - Osteonecrosis of the jaw (ONJ) following bisphosphonate use is well documented.
      However, to our knowledge, there are few cases reported on ONJ related to the use
      of other pharmaceutical agents, such as denosumab--a monoclonal antibody that is
      prescribed for the treatment of osteoporosis and is used as an anti-cancer agent.
      Here we present the first case in the UK of a patient who has developed ONJ
      following treatment with denosumab. The purpose of this report is to highlight
      the potential effects of this monoclonal antibody on bone turnover and the
      subsequent results of osteonecrosis of the jaw. It is hoped that this will allow
      early recognition by medical and dental practitioners, and appropriate referral
      and treatment. Clinical Relevance: Readers should be aware of other causes of
      osteonecrosis of the jaw.

PMID- 25073228
TI  - Current status of conservative treatment of deep carious lesions.
AB  - Traditionally, deep carious lesions are treated by removal of all carious tissue,
      which may lead to pulp exposure. To minimize this risk, conservative carious
      tissue removal techniques have been proposed, including partial removal and
      stepwise excavation. However, there is no consensus in the literature about which
      is the better technique. Thus, the aim of this article is to describe and discuss
      the main techniques for carious tissue removal, according to scientific evidence.
      It was observed that both stepwise excavation and partial carious tissue removal
      presented lower pulp exposure rates and higher success rates. Clinical Relevance:
      Clinicians must be aware that conservative carious tissue removal techniques,
      such as stepwise excavation and partial carious tissue removal, present lower
      pulp exposure rates and higher success rates than traditional methods.

PMID- 25073229
TI  - Midline diastema and its aetiology--a review.
AB  - Maxillary midline diastema is a common aesthetic complaint of patients. Treating
      the midline diastema is a matter of concern for practitioners, as many different
      aetiologies are reported to be associated with it. The appearance of midline
      diastema as part of the normal dental development makes it difficult for
      practitioners to decide whether to intervene or not at an early stage. The aim of
      this article is to review the possible aetiology and management options which
      will help the clinician to diagnose, intercept and to take effective action to
      correct the midline diastema. The available data shows that an early intervention
      is desirable in cases with large diastemas. Treatment modality, timing and
      retention protocol depends on the aetiology of the diastema. Therefore, priority
      needs to be given to diagnosing the aetiology before making any treatment
      decisions. Clinical Relevance: This article aims to determine and evaluate the
      aetiology and possible treatment options of midline diastema.

PMID- 25073230
TI  - Periodontal disease in general practice--an update on the essentials.
AB  - Periodontal disease has a wide spectrum of presentation, any of which can have an
      effect on the patient's dental well-being and overall quality of life. This
      sporadic but sometimes rapidly progressing condition can easily be missed in a
      busy general practice setting. It is essential that the correct diagnosis is made
      and our duty of care to the patient fulfilled. If the condition, along with the
      treatment options and appropriate advice, is not explained to the patient, the
      individual may well feel that he/she has been let down by the professional person
      trusted over many years. Clinical Relevance: This article discusses the screening
      and referral of periodontal patients, taking into account the medico-legal
      challenges that are currently faced by general dental practitioners (GDPs).

PMID- 25073231
TI  - Clinical challenges Q&A. 1. Sore gums.

PMID- 25073232
TI  - Technique tips--active lingual retainer.

PMID- 25073233
TI  - Thoracic involvement in systemic primary vasculitis: radiological patterns and
      follow-up.
AB  - Systemic primary vasculitides are rare idiopathic diseases causing an
      inflammatory injury to the vessel walls. A pulmonary involvement is frequent, and
      chest-CT is the imaging technique of reference in its assessment. An extremely
      wide variety of parenchymal, vascular and airways abnormalities, has been
      described and diagnosis can be challenging: knowledge of clinical data and a
      close cooperation with the referring physician is often crucial. The aim of this
      work is to describe the most common typical and atypical CT features of pulmonary
      vasculitis and their possible changes over time and therapy, focusing on the
      differential diagnosis with other inflammatory/infectious or neoplastic diseases.

PMID- 25073234
TI  - Clinical significance of signal changes in the quadratus femoris muscle on MR.
AB  - OBJECTIVES: To evaluate the clinical significance of quadratus femoris muscle
      signal changes (QFMC) on MRI. METHODS: 204 consecutive bilateral MRI hip
      examinations (132 female, 72 male) were reviewed in retrospect for QFMC.
      Inclusion imaging parameters were edema or atrophy of the quadratus femoris
      muscle. The presence or absence of symptoms and additional ipsilateral and/or
      contralateral imaging findings were used to differentiate between isolated
      symptomatic, co-incidental and asymptomatic QFMC. RESULTS: 24 (11.8%) patients
      and 30 (7.3%) hips demonstrated QFMC. Atrophy was present in 5 symptomatic hips.
      Female to male ratio was 23:1. Isolated symptomatic QFMC: 4 hips (13.3%), 1
      bilateral. Clinical symptoms in this group were non-specific greater trochanter
      pain and stiffness of the hip. Co-incidental QFMC: 19 symptomatic hips,
      ipsilateral associated findings present in 18 hips (94.7%) and contralateral
      additional findings present in 8 hips (42.1%). Asymptomatic QFMC: 7 hips (23.3%),
      ipsilateral associated asymptomatic findings in 5 hips (71.4%) and contralateral
      associated symptomatic findings in 6 hips (85.7%). Edema around the greater
      trochanter and hamstring insertions were the most frequent associated findings.
      CONCLUSION: In this study, most cases of QFMC were co-incidental or asymptomatic.
      In isolated symptomatic QFMC clinical complaints were non-specific. Atrophy was
      found only in the symptomatic hips.

PMID- 25073235
TI  - Primary aortic thrombosis: role of enhanced multislice CT demonstrated in three
      exceptional cases.
AB  - Primary aortic thrombosis remains a rare entity that can be defined as clotting
      of the vessel without any obvious atheromatous lesion. Cancer chemotherapy,
      cocaine intake, essential thrombocythemia, some hypercoagulable states, heparin
      induced thrombocytopenia, inflammatory disease of the digestive tract and acute
      pancreatitis are, beside some cases of rather unknown etiology, the causes of
      primary aortic thrombosis. Intravenous contrast-enhanced multislice CT, which is
      widely available, noninvasive and affordable in terms of cost, is the imaging
      modality of choice for the investigation of primary aortic thrombosis and the
      assessment of potential complications. Three cases due to chemotherapy,
      antiphospholipid syndrome and acute pancreatitis are reported.

PMID- 25073236
TI  - Diffuse pseudoangiomatous stromal hyperplasia of the breast: a case report and a
      review of the radiological characteristics.
AB  - Pseudoangiomatous stromal hyperplasia is a benign mesenchymal tumor of the
      breast. It is a rare condition and until a few years mainly described in
      pathological and surgical literature. Here, we provide a case report of PASH and
      an overview of its radiological features.

PMID- 25073237
TI  - Primary intraosseous manifestation of Rosai-Dorfman disease: 2 cases and review
      of literature.
AB  - Rosai-Dorman disease (RDD) is a rare disorder of proliferative histiocytes with
      an unknown etiology. It is also known as sinus histiocytosis with massive
      lymphadenopathy. Most patients present with painless cervical lymphadenopathy due
      to accumulation of histiocytes in the lymph nodes, often in conjunction with
      fever, elevated leukocyte count and erythrocyte sedimentation rate. Isolated
      skeletal involvement is very rare.

PMID- 25073238
TI  - Unilateral giant cell lesion of the jaw in Noonan syndrome.
AB  - Noonan syndrome (NS) is an etiologically heterogeneous disorder caused by
      mutations in the RAS-MAPK signaling pathway. Noonan-Like/Multiple Giant Cell
      Lesion (NL/MGCL) syndrome is initially described as the occurrence of multiple
      gnathic giant cell lesions in patients with phenotypic features of NS. Nowadays,
      NS/MGCL syndrome is considered a variant of the NS spectrum rather than a
      distinct entity. We report the case of a 14-year-old female patient carrying a
      SOS1 mutation with a unilateral giant cell lesion of the right mandible. Cross
      sectional imaging such as CT and MRI are not specific for the diagnosis of oral
      giant cell lesions. Nonetheless, intralesional scattered foci of low SI on T2-WI,
      corresponding to hemosiderin deposits due to hemorrhage, can help the radiologist
      in narrowing down the differential diagnosis of gnathic lesions in patients with
      NS.

PMID- 25073239
TI  - Endometriosis of the groin: the additional value of magnetic resonance imaging
      (MRI).
AB  - We report a rare case of endometriosis of the groin in a young woman. This case
      shows how difficult the diagnosis of unusual manifestations of endometriosis can
      be. The diagnosis was suspected by a careful history and physical examination.
      Diagnosis was supported by timely performed Magnetic Resonance Imaging, which
      illustrates its additional value. It can be argued that MRI could be the first
      choice of imaging technique for the assessment of young women with nonspecific or
      unexplained complaints of the groin. Even more important is the familiarity of
      physicians other than gynaecologists with rare manifestations of this common
      disease.

PMID- 25073240
TI  - Pancreatic cystic lymphangioma: diagnostic approach with MDCT and MR imaging.
AB  - Lymphangiomas are rare congenital benign tumors arising from the lymphatic system
      mostly encountered in the neck and axillary regions of pediatric patients.
      Pancreatic cystic lymphangiomas very rarely occur in adults. Radiologically, the
      lesion may mimic pancreatic carcinoma and should be considered in the
      differential diagnosis of any patient found to have an abdominal cystic mass. In
      this article, we present a 50-year-old man who presented with pain in the upper
      abdomen, nausea, and abdominal swelling. On computed tomography (CT) and magnetic
      resonance (MR) imaging, a gross septated cystic lesion was detected in the upper
      abdomen which extended from the pancreatic corpus to the left liver lobe. The
      patient underwent complete resection of tumor. Pathology revealed a cystic
      lymphangioma.

PMID- 25073241
TI  - Nora's lesion or bizarre parosteal osteochondromatous proliferation: a rare and
      relatively unknown entity.
AB  - The case of a 34-year-old man with a fast growing hard lump on the fourth digit
      of the right hand is presented. Radiography and MRI of the finger showed the
      radiologic characteristics of a bizarre parosteal osteochondromatous
      proliferation. Pathologic analysis confirmed the radiologic diagnosis.

PMID- 25073242
TI  - Marked myocardial lipoma of the left ventricle free wall.
AB  - We report a rare case of marked myocardial lipoma of the left ventricle free wall
      investigated with echocardiography, CT and comprehensive MRI. The case is a 52
      year-old man with a history of arrhythmia, hypertension and palpitations.
      Echocardiography was normal except for the base of the interventricular septum
      which was slightly thickened. CT and cardiac MRI showed features consistent with
      myocardial lipoma. This is the first report of myocardial lipoma on the left
      ventricle free wall depicted as perfusion defect on MR perfusion imaging.

PMID- 25073243
TI  - Hepatic adenomatosis: MR imaging features.
AB  - Hepatocellular adenomas are rare benign liver neoplasms that commonly occur in
      women with a history of oral contraceptives intake for more than 2 years. Hepatic
      adenomatosis is characterized by the presence of multiple adenomas, arbitrarily >
      than 10, involving both lobes of the liver, without any history of steroid
      therapy or glycogen storage disease. Although the adenomas in liver adenomatosis
      are histologically similar to other adenomas, liver adenomatosis appears to be a
      separate clinical entity. Adenomas in hepatic adenomatosis may be of the
      inflammatory, hepatocyte nuclear factor 1alpha-mutated, or beta-catenin-mutated
      subtype, and accordingly show variable imaging appearances. Hepatic adenomatosis
      carries the risk of impaired liver function, hemorrhage and malignant
      degeneration. We report a case with the inflammatory subtype of hepatic
      adenomatosis in a 39-year-old woman with liver steatosis. The magnetic resonance
      imaging features using extracellular gadolinium chelates and hepatocyte-targeted
      contrast agents are described.

PMID- 25073244
TI  - Dopamine-secreting giant adrenal ganglioneuroma: clinical and diffusion-weighted
      magnetic resonance imaging findings.
AB  - We report a case of a dopamine-secreting giant primary adrenal ganglioneuroma
      (GN) in a 29-year-old male patient. Although the patient was clinically silent,
      the 24-hour urine levels of dopamine, normetanephrine, homovanillic acid and
      vanillyl mandelic acid were elevated. Abdominal ultrasonography and magnetic
      resonance imaging showed a large solid tumor with calcifications and a slightly
      lobular edge on the left adrenal gland. A tumor, 13 x 23 x 25 cm in size, was
      completely resected without morbidity. A 2-year follow-up with computed
      tomography showed that the postoperative course of the patient was uneventful.

PMID- 25073245
TI  - Sulfite oxidase deficiency in a newborn.
AB  - Isolated sulfite oxidase deficiency is a rare, autosomal recessive disease with a
      very poor prognosis. This condition usually presents in the neonatal period and
      is mainly characterized by neurological abnormalities, including refractory
      seizures, abnormal muscle tone, abnormal movements, and marked developmental
      delay. The differentiation from hypoxic-ischemic encephalopathy is difficult
      based on clinical findings alone. We present a neonatal case

PMID- 25073246
TI  - Testicular plasmacytoma, an unusal testicular tumor.
AB  - We report the case of a 78-year-old man with recent diagnosis of Kahler disease
      and a non-tender swollen left hemiscrotum. Ultrasound findings showed an
      intratesticular, hypervascular hypoechoic lesion. MRI imaging demonstrated
      general appearance of a malignant lesion. Specific characteristics however, could
      not be withheld on MRI. Orchidectomy was performed and plasmacytoma was
      demonstrated at pathological examination. Although plasmacytoma of the testis is
      extremely rare, it should be included in the differential diagnosis taking into
      account the ultrasound and MRI appearances, especially in elderly patients with
      known Kahler disease.

PMID- 25073247
TI  - Bilateral lesions of the globus pallidus in a young woman.
AB  - We report a case of stroke due to cocaine abuse in a 30-year-old woman. The
      initial examinations pointing to this diagnosis were CT and MRI. Magnetic
      Resonance Imaging revealed bilateral globus pallidus infarction characterized by
      restricted Diffusion with low ADC values. There was also a partial hemorrhagic
      component confirmed on T2* sequence. After gadolinium injection there was a ring
      enhancement consistent with a blood brain barrier leakage. Similar lesions have
      been described in post hypoxic-anoxic injuries such as following cardiac arrest,
      severe blood loss and CO intoxication.

PMID- 25073248
TI  - Adult intradural lipoma with tethered spinal cord syndrome.

PMID- 25073249
TI  - Aneurysmal bone cyst of the proximal phalanx.

PMID- 25073250
TI  - Flexor tendon tenosynovitis with rice body formation in rheumatoid arthritis.

PMID- 25073251
TI  - Angioleiomyoma of the elbow.

PMID- 25073252
TI  - Burning of an ulcerated breast cancer during MRI: a lesson to be learned.

PMID- 25073254
TI  - LSMS leaders in Washington. Two bills to permanently fix SGR under consideration.

PMID- 25073253
TI  - MR imaging of the knee at 3T--diagnostic performance and comparison with 1.5T.

PMID- 25073255
TI  - How the Physician Payment Sunshine Act could affect practice revenue.

PMID- 25073257
TI  - Anomalous left main coronary artery causing a myocardial infarction in a 14-year
      old boy.
AB  - A 14-year-old boy presented with exertional chest pain and was found to have
      rising cardiac biomarkers. The electrocardiogram revealed ST-segment elevation
      and T-wave inversion in the anterolateral leads. Coronary arteriograms and
      coronary computed tomography (CCT) showed an anomalous left main coronary artery
      originating from the right coronary sinus of Valsalva and coursing intramurally
      within the wall of the aorta between the aorta and the pulmonary trunk. The
      proximal left main was narrow with normal distal left main, left anterior
      descending, and left circumflex coronary arteries. The patient underwent surgical
      de-roofing of the intramural course of the left main artery with relief of his
      symptoms. Coronary artery anomalies have been found in 1.3% of the patients in a
      large arteriographic study. These anomalies are classified on the basis of the
      origin of the coronary arteries, as well as their course and distribution. Many
      of these variations are discovered incidentally at arteriography or autopsy.
      However, some of the anomalies cause symptoms, and a few of them can cause sudden
      cardiac death, even at a young age.

PMID- 25073256
TI  - Emerging trends in free-living amebic infections of the brain: implications for
      organ transplantation.
AB  - This epidemiological review analyzed cases of Naegleria fowleri primary amebic
      meningoencephalitis (PAM) and Balamuthia mandrillaris granulomatous amebic
      encephalitis (GAE) for behavioral and demographic risk factors for pathogen
      exposures and potential transmission by organ transplantation. The Centers for
      Disease Control and Prevention (CDC) Naegleria Workgroup Registry provided 121
      cases of laboratory-confirmed PAM over the period, 1937-2007. The CDC and the
      California Encephalitis Project provided 28 cases of GAE over the period, 1994
      2010. There was a statistically significant increase in clusters of PAM cases
      between the periods, 1937-1996 and 1997-2007. Risk factors for PAM included male
      gender, freshwater exposures, summer exposures, and exposures in southern-tier US
      (United States) states. Risk factors for GAE included male gender, exposures in
      southern-tier US states, Hispanic ethnicity in California, occupational or
      recreational contacts with soil, and recent organ transplantation. Fatal free
      living amebic infections of the brain are increasing today due to more frequent
      environmental, recreational, and occupational exposures; organ transplantation;
      and unanticipated clusters of PAM due to N. fowleri inoculations following nasal
      sinus irrigation using neti pots filled with municipal tap water. Potential organ
      donors dying from meningoencephalitis of unexplained causes should be screened
      for free-living amebic infections of the brain capable of hematogenous
      dissemination in organ recipients.

PMID- 25073258
TI  - An unusual case of mycosis fungoides with high proliferation index and C-MYC/8q24
      translocation.
AB  - Mycosis fungoides is the most common entity among all cutaneous T cell lymphomas.
      Herein, we report for the first time a case of mycosis fungoides in a 51-year-old
      man with aggressive clinical course and confirmed C-MYC/8q24 translocation.
      Review of the literature reveals that dermal Ki-67 proliferation index not only
      correlates with the type and extent of skin involvement and clinical stage, but
      is also an independent adverse prognostic factor. Mycosis fungoides is associated
      with multiple genomic abnormalities, particularly in patients with tumor stage
      and advanced clinical stage, and gain of C-MYC/8q24 is associated with a shorter
      survival. Our patient showed a high dermal Ki-67 level and concomitant C-MYC/8q24
      translocation, which may account for the aggressive clinical course and
      refractoriness to CHOP (cyclophosphamide, doxorubicin, vincristine, and
      prednisone) chemotherapy.

PMID- 25073259
TI  - Littoral cell angioma: review of the literature and case report.
AB  - Littoral cell angioma (LCA), a primary vascular neoplasm originating from splenic
      red pulp littoral cells, was initially thought to be an extremely rare pathology.
      There have been an increasing number of cases reported in the literature.
      However, the etiology and prevalence of LCA is still unclear, partly due to the
      rarity of cases. The association of LCA with internal organ cancers, specifically
      lymphoma, has also been reported. In the patients with a history of
      cancer/lymphoma, the accurate diagnosis of LCA as the cause of the splenomegaly
      is challenging. Here we present a case of LCA in a patient with non-Hodgkin B
      cell lymphoma and alpha-thalassemia trait. To our knowledge, this is the first
      report of the coexistence of LCA and thalassemia and only the second report of
      LCA and marginal-zone non-Hodgkin B-cell lymphoma. We review the literature and
      discuss the radiologic and pathologic findings of this case compared with the
      previously reported cases.

PMID- 25073260
TI  - A case report highlighting the growing trend of Internet-based self-diagnosis of
      "Morgellon's disease".
AB  - "Morgellon's Disease" is a term used to describe a bizarre condition
      characterized by the belief that strange sensations in the skin are due to
      filaments called "Morgellon's Bodies."' The focus of this case report is to
      inform readers of the growing incidence of this psychosomatic condition.
      Unfortunately, self-diagnosis has become increasingly common because of the
      widespread coverage on the Internet. While the validity of the diagnosis is in
      question, the impact on patient's lives is real, often debilitating, and bears
      more examination.

PMID- 25073261
TI  - Treatment of methadone-induced torsades de pointes with lidocaine.
AB  - Methadone maintenance treatment (MMT) is commonly used for chronic pain control
      and for substitution in heroin addicts undergoing rehabilitation. Methadone is
      known to prolong QT interval and sometimes cause torsade de pointes (TdP) and
      ventricular fibrillation (VF). Treatment of TdP by antiarrhythmic drugs that
      prolong QT interval may worsen TdP. To our knowledge, worsening of methadone
      induced TdP by amiodarone has not been reported before. We describe here a case
      of methadone-induced TdP that deteriorated into ventricular fibrillation upon
      treatment with intravenous (IV) amiodarone and resolved after discontinuation of
      amiodarone and treatment with IV magnesium, potassium, and lidocaine.

PMID- 25073262
TI  - ECG of the month. ECG in a dyspneic 54-year-old man. Sinus tachycardia; right
      atrial enlargement; right axis deviation; right ventricular hypertrophy with
      repolarization change.

PMID- 25073263
TI  - Radiology of the month. Headache. Subdural hematoma.
AB  - A 28-year-old woman with a three-year history of epilepsy was evaluated with
      intracranial monitoring, which consisted of two subdural strip electrodes and
      eight depth electrodes. On the third day of monitoring, she developed a headache
      but no focal signs or symptoms.

PMID- 25073264
TI  - Clinical case of the month. A 63-year-old woman with lumbago. Eikenella
      corrodens.
AB  - We present a case of facet joint infection (pyogenic facetitis) due to Eikenella
      corrodens, diagnosed by physical examination, radiography, positive blood
      cultures, and response to antibiotic therapy. E. corrodens is a very rare cause
      of spine infection. There are fewer than 20 such cases reported in the
      literature, only one of which was diagnosed by non-invasive means, and none of
      which were isolated to the facet joint. We briefly review the microbiology of E.
      corrodens in addition to the diagnosis and management of spine infection.

PMID- 25073265
TI  - Pathology case of the month. Swamp-related wound infection. Aeromonas hydrophila.
AB  - A 38 year-old woman with no significant past medical history was brought to the
      emergency department following a motor vehicle rollover and submersion into
      swampy waters alongside a Louisiana interstate. In addition to multiple blunt
      force injuries, she suffered a laceration injury over the right lower extremity,
      which initially required irrigation and sterile dressing. On hospital day two,
      the wound became grossly infected. The wound was swabbed for culture and Gram
      stain, and the patient was empirically started on intravenous
      Piperacillin/tazobactam. Results from the Gram stain showed few white blood cells
      and numerous Gram negative rods. The following day, the wound continued to drain
      purulent material but with a stable zone of erythema. The wound was drained and
      debrided. On hospital day four, the blood agar plate, previously inoculated with
      the wound culture, grew the colonies shown in the below photograph.

PMID- 25073266
TI  - [Diagnosis and limited operative treatment of multi-segmental lumbar disease].
AB  - OBJECTIVE: To investigate the diagnosis and effectiveness of limited operative
      treatment for multisegmental lumbar disease. METHODS: Between February 2008 and
      February 2011, 47 patients with multi-segmental lumbar disease were treated,
      including 27 males and 20 females with an average age of 60.3 years (range, 38-82
      years) and a median disease duration of 21 months (range, 6 months to 7 years).
      Based on preoperative clinical manifestation and imaging examination results, the
      possibility of preliminary responsible segment was identified as two levels in 31
      cases (L4,5 and L5, S1 in 22 cases, L3,4 and L4,5 in 6 cases, L2,3 and L3,4 in 3
      cases) and three levels in 16 cases (L3,4, L4,5, and L5, S1 in 9 cases, L1,2,
      L4,5, and L4, S1 in 4 cases, L2,3, L4,5, and L5, S1 in 3 cases). Selective nerve
      root block (SNRB) was used in all cases to identify the responsible segment.
      Based on the results, the patients were treated by limited operative treatment.
      The operation time, intraoperative blood loss, postoperative drainage volume,
      postoperative ambulation time, and complications were recorded. The clinical
      outcome was evaluated according to the visual analogue scale (VAS) scores for
      back and leg pain, Japanese Orthopaedic Association (JOA) scores, and Oswestry
      disability index (ODI). The position of internal fixators and interbody fusion
      were observed through lumbar anteroposterior and lateral X-ray films. RESULTS:
      The responsible segment was identified as single level in 33 cases (L4,5 in 18
      cases, L5, S1 in 11 cases, and L3,4 in 4 cases) and two levels in 10 cases (L4,5
      and L5, S1 in 6 cases, L3,4 and L4,5 in 3 cases, L2,3 and L4,5 in 1 case) by
      SNRB. After SNRB, 4 cases did not receive surgical treatment because of a low
      relief rate of less than 30%. The operations were performed successfully in all
      43 patients. The mean operation time was 101.9 minutes; the mean intraoperative
      blood loss was 164.5 mL; the mean postoperative drainage volume was 238.9 mL; and
      the mean postoperative ambulation time was 38.2 hours. There was no complication
      of nerve injury or incision infection. All 43 patients were followed up 12-36
      months (mean, 19.3 months). The VAS scores, JOA scores, and ODI after operation
      were significantly improved when compared with preoperative ones (P < 0.05). The
      postoperative JOA recovery rates were 62.2% +/- 12.6%, 63.4% +/- 12.4%, and 68.6%
      +/- 14.6% at 3, 6 months, and last follow-up respectively, showing no significant
      difference (F = 2.841, P = 0.062). The postoperative X-ray films showed that the
      internal fixators were in good position without loosening or fracture, and the
      interbody fusion was good. CONCLUSION: After identifying the responsible segment
      by SNRB in the diagnosis, limited operative treatment is safe and reliable in the
      treatment of multi-segmental lumbar disease. It can relieve compression
      effectively, decrease the range of operation, maintain the spinal stabilization,
      and has a good effectiveness.

PMID- 25073267
TI  - [Effectiveness study on minimally invasive transforaminal lumbar interbody fusion
      assisted with microscope in treatment of lumbar spondylolisthesis].
AB  - OBJECTIVE: To investigate the effectiveness of minimally invasive transforaminal
      lumbar interbody fusion (MI-TLIF) assisted with microscope in treatment of lumbar
      spondylolisthesis. METHODS: Between January 2011 and June 2012, 52 patients with
      lumbar spondylolisthesis underwent MI-TLIF assisted with microscope. There were
      29 males and 23 females with an average age of 46 years (range, 32-67 years). The
      median disease duration was 3.2 years (range, 3 months to 6 years). There were 38
      cases of lumbar isthmic spondylolisthesis and 14 cases of degenerative
      spondylolisthesis; 12 cases had stenosis secondary to lumbar spondylolisthesis.
      The affected segments were L4,5 (29 cases) and L5, S1 (23 cases). According to
      the Meyerding evaluating system, 24 cases were classified as degree I and 28
      cases as degree II. The visual analogue scale (VAS) score and Oswestry disability
      index (ODI) were used for clinical assessment, and the clinical effects were also
      analyzed by Macnab criterion at last follow-up. The radiographic data were used
      to evaluate reduction of spondylolisthesis, including slipping degree, slipping
      angle, and intervertebral space height. The fusion rate was assessed by Suk
      criterion. RESULTS: The operations were performed successfully in all patients.
      No dural tear or cerebrospinal fluid leakage occurred during operation. The
      average operation time was 105 minutes; the average intraoperative blood loss was
      225 mL; the average postoperative drainage volume was 75 mL; and the average
      hospitalization days were 5.5 days. Superficial infection of incision occurred in
      1 case and was cured after change dressing, and primary healing of incision was
      obtained in the others. All patients were followed up 12-26 months (mean, 18
      months). No loosening, breakage, and displacement of pedicle screw and no Cage
      dislocation occurred by X-ray films after operation. The lumbar spondylolisthesis
      all got good correction. The three-dimensional CT showed continuous bone
      trabecula between centrums. The VAS score, ODI, and the slipping degree, slipping
      angle, and intervertebral space height were significantly improved at last follow
      up when compared with preoperative ones (P < 0.05). According to Macnab criterion
      at last follow-up, the results were excellent in 20 cases, good in 29 cases, and
      fair in 3 cases; the excellent and good rate was 94.2%. According to Suk
      criterion for fusion, 49 cases obtained complete fusion and 3 cases got possible
      fusion. CONCLUSION: As long as indications are seized, MI-TLIF assisted with
      microscope is safe and reliable for treatment of lumbar spondylolisthesis
      (Meyerding dergee I or II), and it has the advantage of less injury, less blood
      loss, less complications, and definite short-term effectiveness.

PMID- 25073268
TI  - [Long-term follow-up study on expandable Cage in treatment of degenerative lumbar
      disease].
AB  - OBJECTIVE: To explore the long-term effectiveness of expandable Cage in treatment
      of degenerative lumbar disease. METHODS: Between January 2005 and January 2008,
      72 patients with degenerative lumbar disease were treated by expandable Cage and
      followed up for 5 years. Of 72 cases, 41 were male and 31 were female with an
      average age of 40.5 years (mean, 35-65 years), including 35 cases of lumbar
      spinal stenosis, 20 cases of degenerative lumbar instability, and 17 cases of
      serious lumbar intervertebral disc protrusion combined with lumbar instability.
      The disease duration was 6-28 months (mean, 9 months). The affected lumbar
      segments were L3,4 in 6 patients, L4,5 in 37 patients, and L5, S1 in 29 patients.
      The Oswestry disability index (ODI) was used to evaluate the effectiveness before
      and after operation and to calculate the improvement rate. During the follow-up,
      the anteroposterior, lateral, and dynamic X-ray films were taken to evaluate the
      operated segment fusion rate. The intervertebral lordosis angle was measured, and
      adjacent segment degeneration was observed. RESULTS: The operation time was 35-90
      minutes (mean, 65 minutes); the intraoperative blood loss was 200-450 mL (mean,
      280 mL), and all the patients received intraoperative autologous blood
      transfusion; the postoperative bedridden time was 3-7 days (mean, 4.5 days); the
      hospitalization days were 10-18 days (mean, 12 days). No complications of nerve
      root injury, cauda equina injury, or cerebrospinal fluid leakage occurred during
      operation. All patients achieved primary healing of the incisions. All 72
      patients were followed up for 5 years. At 3 months, 1 year, and 5 years after
      operation, the ODI were 8.2 +/- 2.6, 6.9 +/- 1.9, and 6.4 +/- 1.3 respectively,
      showing significant differences when compared with preoperative value (41.5 +/-
      3.5) (P < 0.05); the improvement rates were 87.3% +/- 1.2%, 90.1% +/- 0.8%, and
      91.6% +/- 1.3% respectively, showing no significant difference (F=0.492,
      P=0.375); the intervertebral lordosis angles were (5.1 +/- 1.2), (5.0 +/- 0.5),
      and (5.4 +/- 0.8) degrees respectively, showing no significant difference
      (F=0.570, P=0.453). At 5 years after operation, the intervertebral fusion rate
      was 100%, with no adjacent segment degeneration. CONCLUSION: Using expandable
      Cage to treat degenerative lumbar disease can get stabilization without pedicle
      screw fixation, the good effectiveness is shown after long-term follow-up.

PMID- 25073269
TI  - [Effect of intravenous mannitol or dexamethasone on low back and leg pain after
      lumbar fusion surgery].
AB  - OBJECTIVE: To compare the effect of intravenous 20% mannitol or dexamethasone
      (DM) on low back and leg pain after minimally invasive transforaminal lumbar
      interbody fusion (MI-TLIF). METHODS: Between October 2012 and September 2013, 100
      patients with degenerative lumbar diseases underwent MI-TLIF and percutaneous
      pedicle screw fixation. All patients were randomly divided into 3 groups: 34
      patients received intravenous 20% mannitol after operation (mannitol group); 32
      patients received intravenous DM after operation (DM group); and 34 patients
      received neither dehydrating agent nor steroid after operation (control group).
      There was no significant difference in gender, age, disease duration, clinical
      symptoms, lesion types, and lesion segments between groups (P > 0.05). The serum
      levels of inflammatory factors [tumor necrosis factor a (TNF-alpha), interleukin
      1beta (IL-1beta), and IL-6] were measured by ELISA at pre-operation and 3, 24,
      48, 72, and 96 hours after operation. Low back and leg pain was determined by
      using visual analogue scale (VAS) score after operation. RESULTS: All procedures
      were smoothly performed without major complications of nerve root injury,
      hematoma, or infection. There was no significant difference in operation time and
      intraoperative blood loss between groups (P > 0.05). The VAS score of low back
      pain showed no significant difference between groups at all time points after
      operation (P > 0.05); the VAS score of leg pain in the DM group was significantly
      lower than that in the control group at all time points (P < 0.05), and than
      those in the mannitol group at 3, 24, 48, and 96 hours after operation (P <
      0.05). The serum level of TNF-a in the DM group was significantly lower than that
      in the control group at all time points (P < 0.05), and than that in the mannitol
      group at 3, 48, 72, and 96 hours after operation (P < 0.05). The serum level of
      IL-1beta in the DM group was significantly lower than that in the control group
      at 3, 24, 48, and 72 hours after operation (P < 0.05), and than that in the
      mannitol group at all time points after operation (P < 0.05). The serum level of
      IL-6 in the DM group was significantly lower than that in the control group at 3
      and 24 hours after operation (P < 0.05), and than that in the mannitol group at
      3, 24, and 48 hours after operation (P < 0.05). CONCLUSION: Intravenous 20%
      mannitol may has no effect on postoperative low back and leg pain, while DM can
      markedly relieve leg pain after MI-TLIF.

PMID- 25073270
TI  - [Application of pedicle screw internal fixation for atlantoaxial instability of
      children].
AB  - OBJECTIVE: To investigate the effectiveness of pedicle screw internal fixation
      for the atlantoaxial instability of children. METHODS: Between July 2005 and
      January 2012, 19 cases of atlantoaxial instability were treated, included 10 boys
      and 9 girls with an average age of 7.5 years (range, 4-15 years). The X-ray
      films, CT, and MRI examinations of the cervical spine showed craniocervical
      malformation in 9 cases, congenital os odontoideum in 3 cases, odontoid fracture
      (type II) in 1 case, disruption of transverse ligament in 2 cases, atlantoaxial
      fracture and dislocation in 4 cases; and spinal cord injury in 8 cases, according
      to the American Spinal Cord Injury Association (ASIA) impairment scale, 1 case
      was rated as grade B, 2 as grade C, and 5 as grade D. Preoperative skull traction
      was performed routinely on all cases, and complete reduction was achieved in 17
      cases, no reduction in 2 cases. In 17 patients who achieved complete reduction,
      pedicle screw internal fixation was used through posterior approach, including
      occipitocervical fusion and fixation in 5 cases, and atlantoaxial fusion and
      fixation in 12 cases; in 2 patients with no reduction, pedicle screw internal
      fixation was used through posterior approach (atlantoaxial fusion and fixation)
      after release by transoral approach. RESULTS: The operation was successfully
      performed in all patients. The mean operation time was 89 minutes; the mean
      intraoperative blood loss was 95 mL; the mean postoperative drainage volume was
      73 mL; and the mean hospitalization days were 14 days. The patients were followed
      up 6-27 months (mean, 18.3 months). Satisfactory atlantoaxial fusion was
      obtained, and bone fusion was obtained at 3-7 months after operation (mean, 4.5
      months). No breakage of screw or rods and re-dislocation occurred during follow
      up. At last follow-up, the cervical range of motion (CROM) of the left and right
      rotation were (62.0 +/- 5.9) degrees and (63.9 +/- 3.8) degrees respectively in 5
      patients receiving occipitocervical fusion and fixation, showing significant
      difference when compared with the values of normal children [(72.3 +/- 7.0)
      degrees and (74.1 +/- 7.6) degrees, respectively] at the same age (t = -3.915, P
      = 0.018; t = -5.954, P = 0.004). The CROM of the left and right rotation were
      (70.5 +/- 5.8) degrees and (72.7 +/- 4.9) degrees respectively in 14 patients
      receiving atlantoaxial fusion and fixation, showing no significant difference
      when compared with normal children at the same age (t = -1.417, P = 0.180; t = 
      1.021, P = 0.323). The visual analogue scale (VAS) score was significantly
      decreased from 7.8 +/- 1.1 at pre-operation to 3.5 +/- 0.8 at last follow-up (t =
      17.267, P = 0.000). In 8 cases having spinal cord injury, 2 cases were rated as
      grade C, 1 case as grade D, and 5 cases as grade E according to ASIA impairment
      scale. CONCLUSION: Technique of pedicle screw internal fixation has been proven
      to be an effective treatment for the atlantoaxial instability of children. It
      plays an important part in relieving pain and limitation of the cervical region.

PMID- 25073271
TI  - [Treatment of open tile type C pelvic fractures by open reduction and internal
      fixation through anterior and posterior approaches at early stage].
AB  - OBJECTIVE: To explore the effectiveness of open reduction and internal fixation
      through anterior and posterior approaches in treatment of open Tile type C pelvic
      fractures at early stage. METHODS: Between January 2009 and April 2012, 12
      patients with open Tile C pelvic fractures were treated. There were 7 males and 5
      females, aged 6-53 years (median, 31 years). Of 12 cases, 4 were classified as
      Tile type C1, 6 as Tile type C2, and 2 as Tile type C3; 5 were rated as Gustilo
      type II and 7 as Gustilo type III. The injury severity score was 18-57 (mean,
      37.2). The interval of injury and admission ranged from 15 minutes to 3 days
      (median, 50 minutes). The debridement and external fixation were performed at
      first stage; then open reduction and internal fixation were used through anterior
      approach (reconstruction plate) and posterior approach (cannulated lag screws).
      The vacuum sealing drainage was performed during treatment until the wounds
      healed. RESULTS: Delayed healing of incison was obtained in 12 cases because of
      wound infection. Anatomical reduction or approximate anatomical reduction was
      achieved in all 12 cases. The patients were followed up 3-39 months (median, 18
      months). No loosening of internal fixation or fracture displacement was observed
      during follow-up. The fracture healing time was 7-13 weeks (mean, 9.7 weeks). At
      last follow-up, according to the Matta standard, the outcome was excellent in 10
      cases and good in 2 cases; according to Majeed score, the results were excellent
      in 9 cases, good in 1, and poor in 2. CONCLUSION: Early internal fixation
      operation of open Tile type C pelvic fractures can effectively restore the pelvic
      anatomical structure and stability, reduce the complication, and achieve
      satisfactory effectiveness.

PMID- 25073272
TI  - [Effectiveness of very low profile/variable angle locking plate internal fixation
      in treatment of posterior Pilon fractures extending to medial malleolus by
      posteromedial approach].
AB  - OBJECTIVE: To evaluate the effectiveness of very low profile/variable angle
      locking plate (VLP) internal fixation for posterior Pilon fractures extending to
      the medial malleolus by posteromedial approach. METHODS: A retrospective analysis
      was made on the clinical data from 13 patients with posterior Pilon fractures
      extending to the medial malleolus between December 2011 and August 2012. There
      were 4 males and 9 females with an average age of 48.9 years (range, 23-68
      years). Fractures were caused by falling in 9 cases and by traffic accident in 4
      cases. The locations were the left ankle in 6 cases and the right ankle in 7
      cases. According to the Orthopedic Trauma Association (OTA) classification, 6
      cases were rated as type 43B1, 4 cases as type 43B2, and 3 cases as type 43B3.
      Twelve cases had fibular fractures, including 11 cases of Denis-Weber type B, 1
      case of Denis-Weber type C. The interval of injury and operation was 7-14 days
      (mean, 11.4 days). Open reduction was performed and VLP internal fixation was
      used for posterior malleolar fracture by posteromedial approach. RESULTS: Primary
      healing of incision was obtained in all patients. Tibial nerve palsy was observed
      in 2 cases, and was cured after oral administration of mecobalamin. Twelve cases
      were followed up 12-18 months (mean, 14.5 months). According to the Burwell
      Charnley's radiological evaluation system, 11 cases achieved anatomical
      reduction, 1 case achieved fair reduction. The fracture union time was 3-6 months
      (mean, 3.7 months). No loosening or breakage of internal fixation occurred during
      follow-up. According to the American Orthopaedic Foot and Ankle Society (AOFAS)
      ankle-hindfoot scale, the results were excellent in 7 cases, good in 4, and fair
      in 1; the excellent and good rate was 91.7%. CONCLUSION: VLP internal fixation
      for posterior Pilon fractures extending to the medial malleolus by posteromedial
      approach can achieve good short-term effectiveness. The high quality of reduction
      is acquired under direct vision with low rate of soft tissue complications.

PMID- 25073273
TI  - [Treatment of tibial traumatic osteomyelitis with vacuum sealing drainage
      combined with open bone graft].
AB  - OBJECTIVE: To explore the effectiveness of vacuum sealing drainage (VSD) combined
      with open bone graft for tibial traumatic osteomyelitis. METHODS: Between June
      2007 and December 2012, 23 cases of tibial traumatic osteomyelitis were treated,
      including 15 males and 8 females with an average age of 32.5 years (range, 22-48
      years). The time from injury to admission was 7-18 months (mean, 8.6 months).
      There was local bone scarring in 15 cases, the size ranged from 8 cm x 4 cm to 15
      cm x 8 cm. The CT multi-planar reconstruction was carried out preoperatively.
      Eleven cases had segmental bone sclerosis with a length of 1.5 to 3.8 cm (mean,
      2.6 cm); 12 cases had partial bone sclerosis with a range of 1/3 to 2/3 of the
      bone diameter. On the basis of complete debridement, infection was controlled by
      VSD; bone defect was repaired by VSD combined with open bone graft. After there
      was fresh granulation tissue, the wound was repaired by free skin graft or local
      skin flap transfer. RESULTS: Nail infection occurred in 2 cases, which was cured
      after the use of antibiotics. The wound healed at the first stage after
      repairing. All cases were followed up 10-18 months (mean, 13.5 months). In 11
      cases of segmental bone sclerosis, the infection control time was 7-14 days
      (mean, 8.8 days); the bone healing time was 32-40 weeks (mean, 34.4 weeks); and
      the frequency of VSD was 3-6 times (mean, 4.5 times). In 12 cases of partial bone
      sclerosis, the infection control time was 7-12 days (mean, 8.3 days); the bone
      healing time was 24-31 weeks (mean, 27.3 weeks); and the frequency of VSD was 3-5
      times (mean, 3.6 times). Infection recurred in 1 case, and the patient gave up
      the therapy. No infection recurrence was observed in the other patients.
      CONCLUSION: The VSD combined with open bone graft is an effective method for the
      treatment of tibial traumatic osteomyelitis.

PMID- 25073274
TI  - [Selectively upward placement of acetabular implants in patients with
      anatomically abnormal acetabulum during total hip arthroplasty].
AB  - OBJECTIVE: To investigate the method and effectiveness of selectively upward
      placement of acetabular implants in patients with anatomically abnormal
      acetabulum during total hip arthroplasty (THA). METHODS: Twenty-six cases (26
      hips) of anatomically abnormal acetabulum received THA between January 2005 and
      December 2010, including 22 cases of developmental dysplasia of the hip, 3 cases
      of osteonecrosis of the femoral head, and 1 case of post-traumatic arthritis.
      There were 5 males and 21 females with an average age of 52.3 years (range, 35-67
      years). The left hip was involved in 11 cases and the right hip in 15 cases. The
      preoperative Harris score was 45.85 +/- 10.04. The anteroposterior X-ray films
      and CT scan of the pelvis, anteroposterior and lateral X-ray films of the femur,
      and TraumaCad analysis were performed routinely before operation. The principles
      of acetabular implants were that more than 70% of the bone-implant interface was
      covered, and the upward distance of acetabular implant was less than 15 mm.
      RESULTS: Acetabular implants were placed within 5 mm from the anatomical rotation
      center in 11 cases. The upward distance of acetabular implant was 5-10 mm in 8
      cases and was 10-15 mm in 7 cases. No bone fracture or nerve injury was observed
      intraoperatively. All incisions healed by first intention, and no infection or
      lower limb deep venous thrombosis occurred. One case had dislocation at 3 days
      after operation, and was cured after reduction and conservative treatment. The
      follow-up time ranged from 15 to 71 months (mean, 34 months). The Harris score
      was 91.42 +/- 3.59, showing significant difference when compared with
      preoperative score (t = 20.099, P = 0.000). The Harris scores were 92.09 +/- 4.04
      in patients having less than 5 mm upward distance, 91.25 +/- 2.82 in patients
      having 5-10 mm upward distance, and 90.57 +/- 3.95 in patients having 10-15 mm
      upward distance, showing no significant difference (F = 0.377, P = 0.690). No
      loosening or subsidence of the implant was observed by X-ray film during the
      follow-up. CONCLUSION: The acetabular implants should be placed as close to
      anatomical rotation center as possible according to the principle. However,
      appropriate upward distance of the acetabular implants (< or = 15 mm) could be
      acceptable to meet 70% coverage of bone-implant interface and the implant
      stability. A satisfactory mid-term effectiveness can be obtained, but long-term
      effectiveness should be further investigated.

PMID- 25073275
TI  - [Best knee flexion angle through anteromedial portal during anterior cruciate
      ligament reconstruction].
AB  - OBJECTIVE: To investigate the best knee flexion angle by analyzing the length and
      orientation of the femoral tunnel through anteromedial portal (AM) at different
      flexion angles during anterior cruciate ligament (ACL) reconstruction. METHODS:
      Twelve fresh cadaveric knees were selected to locate the center of ACL femoral
      footprint through AM using the improved hook slot vernier caliper, and to locate
      the posterior bone cortex using a diameter 3 mm ball at flexion of 90, 100, 110,
      120, and 130 degrees. The femoral tunnel length, standard coronal and sagittal
      plane angles, and the position relation between exit point and the lateral
      epicondyle were measured; the tunnel orientation on the anteroposterior and
      lateral X-ray films was also measured. RESULTS: With increasing flexion of the
      knee, the femoral tunnel length showed a first increasing and then stable
      tendency; significant difference was found between at flexion of 90 degrees and
      at flexions of 100, 110, 120, and 130 degrees, and between flexions of 100
      degrees and 120 degrees (P < 0.05). The femoral tunnel showed a trend of
      decreasing with coronal angle, whereas gradually increasing with sagittal angle.
      The knee flexion angle had significant difference either among flexions of 90,
      110, and 130 degrees or between flexions of 100 degrees and 120 degrees (P <
      0.05). The exit point of the femoral tunnel located at the lateral epicondyle of
      the femur proximal to posterior region at flexion of 90 degrees in all knees, and
      at flexion of 100 degrees in 7 knees, but it located at the lateral epicondyle of
      the femur proximal to anterior region at flexion of 110, 120, and 130 degrees in
      all knees. As the knee flexion angle increasing, the angle between femoral tunnel
      with the tangent of internal-external femoral condyle on anteroposterior X-ray
      films showed a trend of decreasing gradually, but a trend of increasing gradually
      on lateral X-ray films. On the anteroposterior X-ray films, significant
      differences were found in the angle either among flexions of 90, 110, and 130
      degrees or between flexions of 100 degrees and 120 degrees (P < 0.05). On the
      lateral X-ray films, there were significant differences in the angle among
      flexions of 90, 100, 110, 120, and 130 degrees (P < 0.05). CONCLUSION: During ACL
      reconstruction by AM, 110 degrees is the best flexion angle, which can get the
      ideal femoral tunnel.

PMID- 25073276
TI  - [Analysis of correlation between trabecular microstructure and clinical imaging
      parameters in fracture region of osteoporotic hip].
AB  - OBJECTIVE: To analyze the correlation between the trabecular microstructure and
      the clinical imaging parameters in the fracture region of osteoporotic hip so as
      to provide a simple method to evaluate the trabecular microstructure by a non
      invasive way. METHODS: Between June 2012 and January 2013, 16 elderly patients
      with femoral neck fracture underwent hip arthroplasty were selected as the trial
      group; 5 young patients with pelvic fracture were selected as the control group.
      The hip CT examination was done, and cancellous bone volume/marrow cavity volume
      (CV/MV) was analyzed with Mimics 10.01 software in the control group. The CT scan
      and bone mineral density (BMD) measurement were performed on normal hips of the
      trial group, and cuboid specimens were gained from the femoral necks at the place
      of the tensional trabeculae to evaluate the trabecular microstructure parameters
      by Micro-CT, including bone volume fraction (BV/TV), trabecular number (Tb.N),
      trabecular spacing (Tb.Sp), trabecular thickness (Tb.Th), connect density
      (Conn.D), and structure model index (SMI). The correlation between imaging
      parameters and microstructure parameters was analyzed. RESULTS: In the trial
      group, the BMD value was 0.491-0.698 g/cm2 (mean, 0.601 g/cm2); according to
      World Health Organization (WHO) standard, 10 cases were diagnosed as having
      osteoporosis, and 6 cases as having osteopenia. The CV/MV of the trial group
      (0.670 1 +/- 0.102 0) was significantly lower than that of the control group
      (0.885 0 +/- 0.089 1) (t = -4.567, P = 0.000). In the trial group, CV/MV had
      correlation with BV/TV, Tb.Th, and SMI (P < 0.05); however, CV/MV had no
      correlation with Tb.N, Tb.Sp, or Conn.D (P > 0.05). BV/TV had correlation with
      Tb.Th, Tb.N, Tb.Sp, and SMI (P < 0.05), but it had no correlation with Conn.D
      (P=0.075). There was no correlation between BMD and microstructure parameters (P
      > 0.05). CONCLUSION: CV/MV obviously decreases in the osteoporotic hip, and there
      is a correlation between CV/MV and the microstructure parameters of BV/TV, Tb.Th,
      and SMI, to some extent, which can reflect the variety of the microstructure of
      the trabeculae. There is no correlation between BMD of femoral neck and
      microstructure parameters.

PMID- 25073277
TI  - [Effect of titanium particles on proliferation, differentiation, and
      cytomorphology of osteoblasts].
AB  - OBJECTIVE: To study the effect of titanium particles on the proliferation,
      differentiation, and cytomorphology of osteoblasts, and to explore the possible
      internal relations and mechanism. METHODS: Calvarial osteoblasts were separated
      from 10 newborn Sprague Dawley rats by repeated enzyme digestion, and were
      cultured in vitro. The cells were identified by alkaline phosphatase (ALP)
      staining and alizarin red staining. The cells at passage 3 were cultured with
      titanium particles culture medium at concentrations of 0.01, 0.05, 0.1, 0.5, and
      1 mg/mL (0.01, 0.05, 0.1, 0.5, and 1 mg/mL groups). The absorbance (A) values
      were detected by cell counting kit 8 at 7 days after cultured to compare the
      effect of titanium particles at different concentrations on proliferation, and
      median lethal concentration was screened out. The expression of collagen type I
      was detected by ELISA to observe the effect of titanium particles on
      differentiation. The osteoblasts co-cultured with titanium particles of median
      lethal concentration (experimental group) for 7 days, and double fluorescence
      staining with FITC-phalloidine and propidium iodide was performed. The
      cytomorphology variation of osteoblasts after swallowing titanium particles was
      observed under laser scanning confocal microscope. The osteoblasts at passage 3
      cultured with culture medium without titanium particles served as control group.
      RESULTS: The cultured cells were identified as osteoblasts by ALP staining and
      alizarin red staining. Different concentrations of titanium particles could
      inhibit osteoblasts proliferation and differentiation in varying degrees, showing
      significant difference when compared with the control group at 7 days after
      culture (P < 0.05). The cell proliferation and differentiation were decreased
      with increased titanium particles concentration; significant differences were
      found between the other groups (P < 0.05) except 0.01 and 0.05 mg/mL groups (P >
      0.05). The median lethal concentration of titanium particles was 0.5 mg/mL. Laser
      scanning confocal microscope showed cellular shrinking, microfilaments
      distortion, pseudopodia contraction of osteoblasts that swallowed titanium
      particles in the experimental group. CONCLUSION: Titanium particles can inhibit
      proliferation and differentiation of osteoblasts. The effect may be related to
      variation of cytomorphology after swallowing titanium particles.

PMID- 25073278
TI  - [Preliminary analysis of differentially expressed genes in steroid-induced
      osteonecrosis of femoral head by gene microarray].
AB  - OBJECTIVE: To screen for the differentially expressed genes in steroid-induced
      osteonecrosis of the femoral head (ONFH) by gene microarray. METHODS: The femoral
      head tissue of ONFH was harvested from 3 patients with steroid-induced ONFH, aged
      25, 31, and 38 years, respectively. Normal tissue was harvested from a 26-year
      old male remains contributor. HE staining of the specimens was performed for
      observing the histology manifestation; the total RNA was extracted for measuring
      the purity; cDNA probe was synthesized by reverse transcription, and then were
      hybridized as the cDNA microarray for scanning of fluorescent signals and
      differentially expressed genes in the tissues. RESULTS: HE staining of normal
      tissue showed complete unit composed of lamellar bone, continuous and complete
      lamellar bone with a concentric arrangement around blood vessels, and normal bone
      cells in the trabecular bone lacuna. In ONFH tissue, adipose tissue increased in
      the medullary cavity, with increased fat cells filling in the medullary cavity
      and extruding capillary, and with decreased bone cells in the bone trabecula,
      which had deeply-stained nuclear chromatin, pyknotic or cracking nucleus, and
      even bone cells disappeared in the part of the bone lacuna, and trabecular bone
      became thin, sparse, interrupt, reduced area in visual field/unit. Total RNA
      extraction electrophoretogram displayed clear bands of 28S and 18S, and the
      brightness ratio of the 28S:18S was 2:1, indicating good total RNA quality. And
      44 genes were differentially expressed, and there were 28 up-regulated genes and
      16 down-regulated genes, including cell/organism defense genes, cell
      structure/motility genes, cell division genes, cell signaling/ cell communication
      genes, cell metabolism genes, gene/protein expression genes, and unclassified
      genes. CONCLUSION: The analysis of the gene expression profile of steroid-induced
      ONFH can provide evidence for the pathogenesis of ONFH.

PMID- 25073279
TI  - [Experimental research of articular cartilage defect repair using micro-fracture
      and insulin-like growth factor 1 in rabbits].
AB  - OBJECTIVE: To investigate the effects of micro-fracture and insulin-like growth
      factor 1 (IGF-1) in treatment of articular cartilage defect in rabbits. METHODS:
      Twenty-four New Zealand white rabbits (aged, 4-6 months; weighing, 2.5-3.5 kg)
      were randomly divided into 4 groups (n = 6): micro-fractures and recombinant
      human IGF-1 (rhIGF-1) treatment group (group A), micro-fracture control group
      (group B), rhIGF-1 treatment control group (group C), and blank control group
      (group D). Full thickness articular cartilage defects of 8 mm x 6 mm in size were
      created in the bilateral femoral condyles of all rabbits. The micro-fracture
      surgery was performed in groups A and B. The 0.1 mL rhIGF-1 (0.01 microg/microL)
      was injected into the knee cavity in groups A and C at 3 times a week for 4 weeks
      after operation, while 0.1 mL saline was injected in groups B and D at the same
      time points. At 4, 12, and 24 weeks, the gross, histological, and
      immunohistochemical observations were performed, and histological score also was
      processed according to Wakitani's score criteria. The collagen contents in the
      repair tissues and normal patellofemoral cartilage were detected by the improved
      hydroxyproline (HPR) method at 24 weeks. Electron microscope was used to observe
      repair tissues of groups A and B at 24 weeks. RESULTS: All animals were survival
      at the end of experiment. At 24 weeks after operation, defect was repaired with
      time, and the repair tissue was similar to normal cartilage in group A; the
      repair tissue was even without boundary with normal cartilage in group B; and the
      repair tissue was uneven with clear boundary with normal cartilage in groups C
      and D. Histological staining showed that the repair tissues had no difference
      with normal cartilage in group A; many oval chondrocytes-like cells and light
      colored matrix were seen in the repair tissues of group B; only a few small
      spindle-shaped fibroblasts were seen in groups C and D. Moreover, histological
      scores of group A were significantly better than those of groups B, C, and D (P <
      0.05) at 4, 12, and 24 weeks. Electron microscope observation showed that a large
      number of lacuna were seen on the surface of repair tissue in group A, and
      chondrocytes contained glycogen granules were located in lacunae, and were
      surrounded with the collagen fibers, which was better than that in group B.
      Collagen content of the repair tissue in group A was significantly higher than
      that in groups B, C, and D (P < 0.05), but it was significantly lower than that
      of normal cartilage (P < 0.05). CONCLUSION: Combination of micro-fracture and
      rhIGF-1 for the treatment of full thickness articular cartilage defects could
      promote the repair of defects by hyaline cartilage.

PMID- 25073280
TI  - [Effectiveness of digital three-dimensional titanium mesh in repairing skull
      defect under temporalis and reconstructing temporal muscle attachment points].
AB  - OBJECTIVE: To investigate the technique and the effectiveness of digital three
      dimensional (3-D) titanium mesh in repairing skull defect under the temporalis
      and reconstructing temporal muscle attachment points. METHODS: Between January
      2009 and December 2012, 58 patients with skull defect after decompressive
      craniectomy at the frontal temporal region were treated. Of 58 patients, 33 were
      male and 25 were female, aged 17-62 years (mean, 36.2 years). The disease
      duration was 15 weeks to 25 months (mean, 5.8 months). The size of skull defect
      ranged from 8 cm x 6 cm to 15 cm x 12 cm. The patients underwent skull impairment
      patch surgery with digital 3-D titanium mesh and reconstruction of the temporal
      muscle attachment points at titanium mesh temporal corresponding position.
      RESULTS: The operation time was 60-100 minutes (mean, 87 minutes). After
      operation, 2 cases had slight red swelling with little exudation at skin incision
      margin, which was cured after symptomatic treatment; 2 cases had symptom of
      headache, which disappeared after incision healing; primary healing of incision
      was obtained in the other patients. Fifty-eight patients were followed up 6-24
      months (mean, 16 months). The patients were satisfied with shaping, and had no
      chewing pain. Head CT after operation showed good fixation of titanium mesh and
      titanium nail, and satisfactory skull shape symmetry; no postoperative
      complication of subcutaneous effusion, intracranial bleeding, titanium mesh
      loosening, or titanium mesh exposure occurred. CONCLUSION: The surgery technique
      of digital 3-D titanium mesh to repair skull defect in frontal temporal region
      and to reconstruct temporal muscle attachment points at the corresponding
      position of titanium mesh, basically can obtain anatomical reduction of the
      skull, frontal temporal, and each layer of scalp. It has the advantages of less
      complication, less titanium nail, and satisfactory shape.

PMID- 25073281
TI  - [Effectiveness of a suture bridge technique for repair of quadriceps tendon
      rupture in uraemic patients].
AB  - OBJECTIVE: To investigate the effectiveness of a suture bridge technique for
      quadriceps tendon rupture repair in uraemic patients. METHODS: Between March 2010
      and September 2012, 10 uraemic patients (14 sides) with quadriceps tendon rupture
      were treated with the suture bridge technique. Of them, 8 were male and 2 were
      female, aged from 30 to 62 years (mean, 54.2 years). The duration of uremia was 3
      11 years (mean, 5.5 years): the duration of quadriceps tendon rupture was 5 days
      to 2 months (median, 12 days). Six cases had a trauma history, and one case had
      diabetes. The left side was involved in 2 cases, the right side in 4 cases, and
      both sides in 4 cases. The active range of motion (ROM) of the knees was (115.0
      +/- 8.3) degrees in flexion, and (72.5 +/- 21.2) degrees in extension. Lysholm
      score was 19.5 +/- 16.3. X-ray films showed downward shifting of patella. MRI
      revealed discontinuity between distal quadriceps tendon and upper pole of
      patella. RESULTS: The operation time was 30-50 minutes (mean, 40.3 minutes).
      Primary healing of incision was obtained in all patients without complications.
      All patients were followed up 12-25 months (mean, 16.3 months). There was no re
      rupture of quadriceps tendon or loosening of internal fixation during follow-up.
      At last follow-up, the active ROM of the knees was (121.0 +/- 7.9) degrees in
      flexion, showing no significant difference when compared with preoperative one (t
      = -2.075, P =0.058); the active ROM was (8.2 +/- 6.1) degrees in extension,
      showing significant difference when compared with preoperative one (t = 11.702, P
      = 0.000). Lysholm score was 84.6 +/- 12.4, showing significant difference when
      compared with preoperative score (t = -16.226, P = 0.000). According to the
      American Knee Society score (KSS), the results were excellent in 4 sides, good in
      9 sides, and fair in 1 side, and the total excellent and good rate was 92.9%. At
      last follow-up, the active ROM of the knee, Lysholm score, and KSS score were
      significantly better in young patients (< 45 years) than in elder patients (> or
      = 45 years), and in patients receiving early operation (< 2 weeks) than in
      patients receiving late operation (> or = 2 weeks) (P < 0.05). CONCLUSION: For
      fewer traumas and early functional exercise after operation, the suture bridge
      technique benefits functional restoration of knee joint in uraemic patients.
      Operation chance and age seem to be important factors to the results. Early
      operation should be considered when quadriceps tendon ruptured.

PMID- 25073282
TI  - [Median nerve constrictive operation combined with tendon transfer to treat brain
      paralysis convulsive deformity of hand].
AB  - OBJECTIVE: To evaluate the effectiveness of the median nerve constrictive
      operation combined with tendon transfer to treat the brain paralysis convulsive
      deformity of the hand. METHODS: The clinical data from 21 cases with brain
      paralysis convulsive deformity of the hand were analyzed retrospectively between
      August 2009 and April 2012. Of them, there were 13 males and 8 females with an
      average age of 15 years (range, 10-29 years). The causes of the convulsive
      cerebral palsy included preterm deliveries in 11 cases, hypoxia asphyxia in 7,
      traumatic brain injury in 2, and encephalitis sequela in 1. The disease duration
      was 2-26 years (mean, 10.6 years). All the 21 patients had cock waists, crooking
      fingers, and contracture of adductors pollicis, 12 had the forearm pronation
      deformity. According to Ashworth criteria, there were 2 cases at level I, 5 cases
      at level II, 8 cases at level III, 4 cases at level IV, and 2 cases at level V.
      All patients had no intelligence disturbances. The forearm X-ray film showed no
      bone architectural changes before operation. The contraction of muscle and
      innervation was analyzed before operation. The median nerve constrictive
      operation combined with tendon transfer was performed. The functional activities
      and deformity improvement were evaluated during follow-up. RESULTS: After
      operation, all the patients' incision healed by first intension, without muscle
      atrophy and ischemic spasm. All the 21 cases were followed up 1.5-4.5 years
      (mean, 2.3 years). No superficial sensory loss occurred. The effectiveness was
      excellent in 13 cases, good in 6 cases, and poor in 2 cases, with an excellent
      and good rate of 90.4% at last follow-up. CONCLUSION: The median nerve
      constrictive operation combined with tendon transfer to treat brain paralysis
      convulsive deformity of the hand can remove and prevent the recurrence of spasm,
      achieve the orthopedic goals, to assure the restoration of motor function and the
      improvement of the life quality.

PMID- 25073283
TI  - [Risk factors of hidden blood loss in internal fixation of intertrochanteric
      fracture].
AB  - OBJECTIVE: To analyze the associated risk factors of hidden blood loss in the
      internal fixation of intertrochanteric fracture. METHODS: A retrospective
      analysis was made on the clinical data of 317 cases of intertrochanteric
      fractures which were treated by internal fixation between January 1993 and
      December 2008. There were 154 males and 163 females with an average disease
      duration of 4.58 days (range, 7 hours to 33 days); the age was (69.86 +/- 15.42)
      years; the average height was 1.64 m (range, 1.50-1.84 m); and the average weight
      was 62.26 kg (range, 39-85 kg). Of them, intramedullary fixation was used in 203
      patients and extramedullary fixation in 114 patients. The operation time was
      (61.99 +/- 18.25) minutes. The red blood cell transfusion was given to 84
      patients, and the transfusion amount was 200-1 000 mL. The drainage volume was 0
      750 mL (mean, 61.85 mL). Hidden blood loss was calculated through change of
      hematocrit level before and after operation. The multiple linear regression was
      performed to analyse the risk factors of hidden blood loss. RESULTS: The total
      blood loss was (918.60 +/- 204.44) mL, the hidden blood loss was (797.77 +/-
      192.58) mL, and intraoperative visible blood loss was (257.32 +/- 271.24) mL.
      Single factor analysis showed hidden blood loss was significantly higher in
      variables as follows: gender, age, injury cause, fracture type, American
      anesthesiologists grading, anesthesia mode, hypertension, diabetes, disease
      duration, operation time, intraoperative transfusion of red blood cells, and
      fixation type. Multiple linear regression showed age, fracture type, anesthesia
      mode, and fixation type were significant risk factors. CONCLUSION: The risk
      factors of hidden blood loss are advanced age (> 60 years), unstable fracture,
      general anesthesia, and imtramedullary fixation. Especially in elder patients
      with unstable fracture treated by intramedullary fixation under general
      anesthesia, hidden blood loss is more significant.

PMID- 25073284
TI  - [Correlation analysis of bone marrow edema degree and serum inflammatory factors
      change with knee joint pain symptoms in patients with bone contusion around the
      knee joint].
AB  - OBJECTIVE: To explore the correlation between the degree of bone marrow edema
      (BME) and the content change of tumor necrosis factor alpha (TNF-alpha) and
      matrix metalloproteinase 3 (MMP-3) and the knee pain symptoms in patients with
      bone contusion around the knee joint. METHODS: Thirty patients (30 knees) of bone
      contusion around the knee joint were chosen as the trial group between October
      2009 and April 2012. According to visual analogue scale (VAS), 30 patients were
      divided into mild group (10 cases), moderate group (10 cases), and severe group
      (10 cases); according to MRI morphological changes, the patients were divided
      into type I group (12 cases), type II group (11 cases), and type III group (7
      cases). Ten patients (10 knees) with soft tissue injury of the knee were chosen
      as control group. No significant difference was found (P > 0.05) in gender, age,
      causes, side, and admission time after injury between 2 groups. The serum
      contents of MMP-3 and TNF-alpha were detected and statistically analysed between
      different degrees of pain groups and between different degrees of BME groups.
      Correlation was analysed between BME and inflammatory factor changes and VAS
      score. RESULTS: The MMP-3 and TNF-alpha contents in trial group [(29.580 +/-
      6.870) (microg/L and (23.750 +/- 7.096) ng/L] were significantly higher than
      those in control group [(8.219 +/- 1.355) microg/L and (6.485 +/- 1.168) ng/L] (t
      = 9.686, P = 0.000; t = 7.596, P =0.000). The MMP-3 and TNF-alpha contents in
      patients with different degrees of pain and BME were significantly higher than
      those in patients of control group (P < 0.05), and significant difference was
      found between patients with different degrees of pain (P < 0.05), but no
      significant difference between patients with different degrees of BME (P > 0.05).
      Multiple linear regression analysis showed that TNF-alpha content was
      significantly correlated with VAS score (P = 0.000). CONCLUSION: Knee pain
      symptoms are not related to the degree of BME in patients with bone contusion
      around the knee joint. Inflammatory factor TNF-alpha content is the main
      influence factor of knee joint pain symptoms.

PMID- 25073285
TI  - [Analysis of risk factors of axial symptoms after single door laminoplasty for
      cervical myelopathy].
AB  - OBJECTIVE: To investigate the risk factors of axial symptoms after single door
      laminoplasty for cervical myelopathy. METHODS: A retrospective analysis was made
      on the clinical data of 102 patients with cervical myelopathy who underwent
      single door laminoplasty and were accorded with selective standard between
      February 2009 and October 2011. There were 59 males and 43 females, aged 35 to 72
      years (mean, 58 years). The disease duration was 1-70 months (mean, 18 months).
      The operated segments included C3-7 in 58 cases, C3-6 in 23 cases, C4-7 in 15
      cases, and C3-5 in 6 cases. The visual analogue scale (VAS) was used to determine
      whether the patient had axial symptoms (group A) or not (group B). The logistic
      regression analysis was used to analyze the risk factors of postoperative axial
      symptoms by assessing the following indexes: preoperative VAS score, preoperative
      Japanese Orthopaedic Association (JOA) score, gender, age, disease duration,
      operated segment, operation time, intraoperative blood loss, wearing collar time,
      preoperative encroachment rate of anterior spinal canal, preoperative cervical
      curvature, and preoperative cervical range of motion. RESULTS: A total of 102
      cases were followed up 18-26 months (mean, 24 months). And no postoperative
      spinal cord injury, cerebrospinal fluid leakage, or infection occurred. Of 102
      cases, 50 had axial symptoms (group A) and 52 had no axial symptoms (group B).
      There were significant differences in age, wearing collar time, preoperative
      cervical range of motion, preoperative cervical curvature, and preoperative
      encroachment rate of anterior spinal canal between 2 groups (P < 0.05), but no
      significant difference was found in preoperative JOA score and VAS score, blood
      loss, gender, disease duration, operated segment, and operation time (P > 0.05).
      The logistic regression analysis showed that the increased preoperative
      encroachment rate of anterior spinal canal, reduced preoperative cervical
      curvature, and preoperative cervical range of motion loss were the risk factors
      for cervical axial symptoms. CONCLUSION: Age, wearing collar time, preoperative
      cervical range of motion, preoperative encroachment rate of anterior spinal
      canal, and preoperative cervical

PMID- 25073286
TI  - [Differentiation of bone marrow mesenchymal stem cells into insulin producing
      cells induced by rat injured pancreatic tissue extract].
AB  - OBJECTIVE: To investigate the effects and mechanisms of differentiation of bone
      marrow mesenchymal stem cells (BMSCs) into insulin producing cells (IPCs) induced
      by injured pancreatic tissue extract of rat. METHODS: Eighty 6-week-old Sprague
      Dawley rats were selected. Forty rats underwent removal of 60% pancreas and the
      injured pancreas tissue was obtained after 48 hours to prepare the injured
      pancreatic tissue extract; and normal pancreatic tissue extract was prepared from
      the other 40 rats. The BMSCs were isolated from the tibia and femur of 4-week-old
      Sprague Dawley rats. BMSCs at passage 3 were co-cultured with rat injured
      pancreatic tissue extract as experimental group, with rat normal pancreatic
      tissue extract as normal control group, and with cell culture medium as blank
      control group for 14 days. The expressions of pancreas development related genes
      and proteins were detected, and cell morphological changes were observed. Then
      the C peptide positive cell rate was detected by flow cytometry analysis and
      insulin secretion levels were detected by glucose stimulation experiment at 14
      days. RESULTS: Injured pancreatic tissue extract can induced BMSCs
      differentiating into IPCs. The pancreatic development related genes of pancreatic
      duodenal homeobox 1 (PDX-1), islet 1, Nkx6.1, glucose transporter type 2,
      proprotein convertase 2, neurogenin 3, and somatostatin were expressed
      sequentially in the differentiation process of experimental group; mature
      pancreatic proteins of PDX-1, insulin, C peptide, Nkx6.1 also were expressed. But
      there was no morphological changes and expression of pancreatic development
      related genes and proteins in normal control and blank control groups. The C
      peptide positive cell rate of experimental group (13.8% +/- 1.8%) were
      significantly higher than those of normal control and blank control groups (1.6%
      +/- 0.4%) (P < 0.05). The insulin secretion of experimental group was
      significantly higher than that of normal control and blank control groups (P <
      0.05), but it was 1/40 and 1147 of natural islet cells (P < 0.05). CONCLUSION:
      After pancreatic injury, injured pancreas would secrete transcription proteins
      related to development, differentiation, and repair of pancreas, which can
      promote the differentiation of BMSCs into IPCs.

PMID- 25073287
TI  - [Differentiation of C17.2 neural stem cells into neural cells induced by serum
      free conditioned medium of olfactory ensheathing cells and cell viability
      detection of differentiated cells].
AB  - OBJECTIVE: To study the possibility of the C17.2 neural stem cells (NSCs)
      differentiating into neural cells induced by serum-free condition medium of
      olfactory ensheathing cells (OECs) and to detect the cell viability of the
      differentiated cells. METHODS: OECs were isloated and cultured from the olfactory
      bulbs of 3-day-old postnatal mouse to prepare serum-free condition medium of
      OECs. After C17.2 NSCs were cultured with H-DMEM/F12 medium containing 15% FBS
      and the cell fusion reached 80%, the 3rd passage cells were induced by serum-free
      condition medium of OECs in the experimental group, by H-DMEM/F12 in the control
      group, and non-induced C17.2 NSCs served as the blank control group. The growth
      condition of cells was observed with inverted microscope. After 5 days, the
      immunofluorescence staining [microtubule-associated protein 2 (MAP-2) and beta
      tubulin-III] and Western blot (Nestin, beta-tubulin-III, and MAP-2) were carried
      out to identify the neural cells derived from NSCs. The cell viabilities were
      measured by MTT assay and the quantity of lactate dehydrogenase (LDH) release in
      the medium. RESULTS: In the experimental group, the C17.2 NSCs bodies began to
      contract at 24 hours after induction, and the differentiated cells increased
      obviously with long synapse at 3 days after induction; in the control group, the
      cell morphology showed no obvious change at 24 hours, cell body shrinkage,
      condensation of nuclear chromatin, and lysis were observed at 3 days. The
      immunofluorescence staining showed that beta3-tubulin-III and MAP-2 of C17.2 NSCs
      were positive at 5 days after induction, and Western blot suggested that the
      expression of Nestin protein declined significantly and the expressions of beta
      tubulin-III and MAP-2 protein were increased in the experimental group, showing
      significant differences when compared with those in the control group and blank
      control group (P < 0.05). The LDH release and the cell viability were 130.60% +/-
      6.86% and 62.20% +/- 3.82% in the experimental group, and were 178.20% +/- 5.44%
      and 18.00% +/- 3.83% in the control group respectively, showing significant
      differences between 2 groups (P < 0.05). The LDH release and the cell viability
      of experimental group and control group were significantly lower than those of
      blank control group (100%) (P < 0.05). CONCLUSION: Neurotrophic factors from OECs
      play an important role in inducing C17.2 NSCs differentiation into neural cells
      and keeping the viability of differentiated cells after induction.

PMID- 25073288
TI  - [Effect of mechanical tension on expressions of RhoA/Rho associated protein
      kinases in rat tendon stem cells in vitro].
AB  - OBJECTIVE: To investigate the effect of different mechanical tensions on the
      expressions of RhoA/Rho associated protein kinases (ROCK) in rat tendon stem
      cells (TSCs). METHODS: TSCs were isolated from the tendon tissue of male Sprague
      Dawley rats (aged, 2-3 months; weighing, 200-250 g) by enzymatic digestion method
      and cultured for 2-3 passages, then seeded on micro groovdishes. The 4% (4%
      stretch group) and 8% (8% stretch group) mechanical stretching was performed for
      4 hours every day at 1 Hz. After 1, 2, and 3 days, the protein and mRNA
      expressions of RhoA and ROCK were measured by Western blot and real-time
      quantitative PCR. The cell proliferation was measured by cell counting kit 8. The
      cells were not stretched as control group. RESULTS: The TSCs at passage 2 showed
      a cobble-stone shape and aggregation growth; TSCs seeded on micro groovdishes
      showed random growth, and the cells grew along the stretching direction after
      mechanical stretching. The mRNA expressions of RhoA and ROCK in control group,
      4%, and 8% stretch groups showed an increasing tendency at 1, 2, and 3 days,
      showing significant difference between groups (P < 0.05). The protein expressions
      of RhoA and ROCK in 4% and 8% stretch groups were similar to those in control
      group at 1 day (P > 0.05), but the expressions in 4% and 8% stretch groups showed
      an increasing tendency at 2 and 3 days, which were significantly higher than
      those in control group (P < 0.05). The cell proliferation of 8% stretch group was
      significantly lower than that of 4% stretch group and control group at each time
      point (P < 0.05), but no significant difference was found between 4% stretch
      group and control group (P > 0.05). CONCLUSION: The expressions of RhoA and ROCK
      of rat TSCs are positively correlated with stretch intensity. So RhoA/ROCK may be
      an important molecule in TSCs after mechanical stretching.

PMID- 25073289
TI  - [Preliminary study on stromal vascular fraction promoting angiogenesis and tissue
      regeneration in tissue engineering chamber].
AB  - OBJECTIVE: To evaluate the mechanism of stromal vascular fraction (SVF) promoting
      angiogenesis and tissue regeneration in tissue engineering chamber. METHODS:
      Twenty-four 6-month-old New Zealand white rabbits, male or female, weighing 2.5
      2.8 kg, were selected. Thoracic dorsal arteriovenous bundle combined with
      collagen type I scaffold was transplanted to dorsal side, and wrapped by
      cylindrical hollow silicone chamber; all animals were randomly divided into the
      experimental group (n = 12) and the control group (n = 12). SVF was isolated from
      the back fat pads of rabbits in experimental group and labelled with DiI at 2
      weeks after operation. The 1 mL cell suspension (1 x 10(6) cells/mL) and equal
      saline were injected into the chamber in experimental group and control group,
      respectively. The regenerative tissues were harvested for general observation and
      HE staining at 2 and 4 weeks after injection: and immunofluorescent staining was
      carried out in experimental group at 4 weeks. RESULTS: At 2 weeks after
      injection, the regenerative tissue was cylindrical; obvious vessel network and
      incompletely degradable collagen scaffold could be seen on the surface of the new
      tissue in 2 groups. The volume of new tissue was (0.87 +/- 0.11) mL in
      experimental group, and (0.72 +/- 0.08) mL in control group at 2 weeks, showing
      significant difference (t = 2.701, P = 0.011). At 4 weeks, little collagen
      scaffold could be seen on the surface in control group, but no collagen scaffold
      in experimental group; the volume of new tissue was (0.74 +/- 0.14) mL in
      experimental group, and (0.64 +/- 0.10) mL in control group, showing no
      significant difference (t = 1.424, P = 0.093). HE staining showed new mature
      vessels at 4 weeks, but no adipose tissue or fat lobulus formed in both groups;
      the capillary density was significantly higher in experimental group than in
      control group at 2 weeks (t = 6.291, P = 0.000) and at 4 weeks (t = 5.445, P =
      0.000). The immunofluorescent staining found that SVF survived and located at the
      edge area after 4 weeks; the expressions of CD31 and DiI were positive in some
      endothelial cells. CONCLUSION: SVF can promote the angiogenesis and tissue
      regeneration in tissue engineering chamber, but it can not differentiate into
      adipocyte spontaneously without adipogenic microenvironment.

PMID- 25073290
TI  - [Immunogenicity of allogeneic freezing periosteum and bone marrow].
AB  - OBJECTIVE: To investigate the immunogenicity of freezing periosteum and bone
      marrow during allogeneic joint transplantation, and to explore proper
      pretreatment of allogeneic joint. METHODS: The allogeneic periosteum and bone
      marrow were harvested from knee joints of 5 New Zealand white rabbits (aged, 6
      months; weighing, 2.6-3.0 kg). After gradient cooling, the tissue was
      cryopreserved for 1 month. The freezing periosteum and bone marrow were grinded
      to pieces after rewarming to prepare the suspension of periosteum and bone
      marrow. Eighteen Chinchilla rabbits (aged, 6 months; weighing, 2.1-2.8 kg) were
      divided into 3 groups randomly: normal saline injection group (group A, n = 6),
      periosteum injection group (group B, n = 6), and bone marrow injection group
      (group C, n=6). The normal saline, periosteum suspension, and bone marrow
      suspension were injected into the peritoneal cavity in groups A, B, and C,
      respectively. The concentrations of interleukin 2 (IL-2), IL-6, and tumor
      necrosis factor alpha (TNF-alpha) in serum and the ratio of CD4' T cell/CD8+ T
      cell in venous blood were measured before injection, at 1 week and 2 weeks after
      injection. RESULTS: There was no significant difference in the concentration of
      IL-2 between before and after injection in the same group (P=0.241), and between
      groups (P = 0.055). The concentration of IL-6 after injection was significantly
      lower than that before injection in the same group (P = 0.040), but no
      significant difference was found between groups (P = 0.357). The concentration of
      TNF-a showed no significant difference between before and after injection in the
      same group (P = 0.925), but the concentration of TNF-a in group B was
      significantly higher than that in groups A and C (P < 0.05). The ratio of CD4+ T
      cell/CD8+ T cell of venous blood had no significant difference between before and
      after operation in the same group (P = 0.248), and between groups (P=0.646).
      CONCLUSION: The freezing periosteum and bone marrow are lowly immunogenic. In
      order to decrease the immunogenicity of the joint, preserving the periosteum and
      removing the marrow cavity are recommended.

PMID- 25073291
TI  - [Progress in surgical management of progressive hemifacial atrophy].
AB  - OBJECTIVE: To summarize recent progress in surgical management of progressive
      hemifacial atrophy (PHA), to analyse the key features of various methods of
      treatment, and to define subjects worthy of further researches. METHODS: The
      publications concerning the etiology and surgical management of PHA were
      reviewed, analyzed, and summarized. RESULTS: Surgical management serves as the
      primary treatment, including flap transposition, tissue flap reconstruction, free
      tissue grafting, prosthetic implants, and other surgical treatments. Each method
      has its own advantages and limitations. At present, comprehensive treatment are
      considered to be the most commonly method for PHA. CONCLUSION: The combined use
      of various surgical methods is the trend of surgical management of PHA; effective
      treatments specific to the etiology and minimally invasive surgical methods are
      still to be developed.

PMID- 25073292
TI  - Passing the boards. Can we safely clear kids from spinal motion restriction?

PMID- 25073293
TI  - Problem-solving for pros. An academic approach to classifying and resolving
      thorny issues can benefit managers.

PMID- 25073294
TI  - How to promote a culture of learning in EMS. Top tips for keeping experienced EMS
      providers engaged in continuing education.

PMID- 25073295
TI  - Critical transport decisions. In time-sensitive emergencies, every moment counts-
      choose wisely.
AB  - Time-sensitive emergencies require early recognition and rapid transport to a
      facility properly equipped to manage the patient's needs. When managing STEMI,
      cardiac arrest, suspected stroke, trauma or a severe sepsis patient, use your
      resources smartly. Manage the patient using all of your capabilities on scene and
      know the destination best prepared to manage the patient upon ED arrival. When it
      makes sense to extend transport time to take a patient to a proper facility, it
      is OK to do so. Considering air medical transport for patients as ground
      transports exceed 30 minutes is reasonable as long as the flight team provides
      transport more rapidly or brings additional care that will improve patient
      outcomes.

PMID- 25073296
TI  - Sox education. Are you doing it just because that's the way you've always done
      it?

PMID- 25073297
TI  - [Adolescent Medicine, quo vadis?].

PMID- 25073298
TI  - [Youth friendly health services: how to promote quality health care for
      adolescents].
AB  - Many young people have difficulties requesting medical or psychosocial support,
      although some badly need it. This difficulty is related to the fact that, as part
      of their search for autonomy, young people prefer to solve their problems by
      themselves. To improve the quality of care, the World Health Organization, UNICEF
      and allied organizations have developed the concept of "Youth friendly health
      services". This concept includes policies and strategies to improve the
      accessibility and flexibility, staff's competence and communication skills, etc.
      Such an approach should not be limited to specialized centers for adolescent
      health. It should be adopted by all health care institutions dealing with young
      people.

PMID- 25073299
TI  - [Specialized adolescent health clinic: who should be referred to it?].
AB  - Adolescent health clinics were created in response to the specific health needs
      of this age-group. Adolescents may present complex health problems which require
      a multidisciplinary and global assessment. The aim of this article is to provide
      an overview of the type of health problems for which adolescents are referred to
      our clinics and the care they receive in response to them.

PMID- 25073300
TI  - [Adolescents with chronic pain: practical assessment and management].
AB  - More than 20% of adolescents in the general population suffer of chronic pain
      mainly headaches, abdominal or musculoskeletal pain. Often, these complaints are
      self limited without impact on adolescent development but the cause of emergency
      consultations, unnecessary costs or inappropriate prescriptions. For a small
      number of adolescents, chronic pain can express psychological suffering or impact
      on growth and physical, cognitive or social development. Continuity of care and
      collaboration among professionals is central. Primary care phyisicians play a
      crucial role (private practice, adolescent clinic...). Efforts should be made to
      increase access to modern approaches of chronic pain taking into account family,
      development as well as aspects related to pain in itself.

PMID- 25073301
TI  - [The major issues of an "assault and battery" report for an adolescent].
AB  - Adolescents who are confronted to violence rarely consult health services about
      this problem. Family maltreatment is the origin of most violence against
      adolescents, but remains very often hidden from the eyes of professionals. The
      "assault and battery" reports produced by emergency services are largely about
      community violence situations. The medical consultation following an assault
      requires a global evaluation of the teenager confronted to violence. This
      evaluation will have to take into account not only the adolescent's requests
      (such as confidentiality), but also professional duties to prevent recidivism.

PMID- 25073302
TI  - [Human papillomavirus: what do young people really know about it?].
AB  - It has been five years since the introduction of the HPV vaccination campagnes in
      Switzerland. Although a majority of young people age 16 to 20 have heard about
      the HPV, many false beliefs regarding this virus and its effects persist, and a
      lot of young people feel insufficiently informed about it. The surveyed
      population is conscious that the HPV is a sexually transmitted infection;
      however, more than 80% do not know that men can also be infected. Preventive
      information must be improved to target men too, in order that everybody
      understands that men, as well as women, are concerned by this infection. Medical
      consultations are the ideal setting to inform young people about the HPV.

PMID- 25073303
TI  - [Which follow-up of the second generation antipsychotic in adolescents?].
AB  - Since the introduction of so called second generation antipsychotic (SGA), the
      prescription of these drugs has been relatively frequent in adolescence. This
      article gives a synopsis of the potential side effects and contra-indications,
      and proposes a practical guideline for the follow-up of these SGAs in adolescent
      and young adults. The main secondary side effects are in metabolic, endocrine,
      neurologic, cardiovascular systems and also on the hematological and liver
      functions. Thus, a strict follow-up should start before the introduction of a SGA
      treatment and should be continued during the time of administration. Since there
      is no common consent for a follow-up in SGA use in adolescents for Europe, this
      article may give a practical guideline for general practitioners and
      pediatricians, including a clinical exam and biological parameters to be
      controlled.

PMID- 25073304
TI  - [Clostridial colitis: diagnosis and strategies for management].
AB  - C. difficile is transmitted in a faecal-oral mode and is widespread in hospital
      environment. Symptoms of Clostridial infection range from asymptomatic carriage
      to life-threatening toxic colitis. The treatment of a Clostridial infection is
      dependent on the seriousness of the symptoms. The diagnosis of the pathogen as
      well as the introduction of an efficient antibiotic therapy is crucial. Oral
      metronidazole is the gold standard in treatment of mild infection. Vancomycin
      should be introduced only in refractory cases or in particular situations. While
      there is a desire to avoid colectomy, inappropriate delay in a very ill patient
      can be fatal. Judgement on when to intervene is difficult and requires analysis
      of the factors which predict outcome with and without surgery. A total abdominal
      colectomy sparing the rectum with end ileostomy is the procedure of choice.

PMID- 25073305
TI  - [Deprived of blood and in induced-hypothermia: will they still be alive?].

PMID- 25073306
TI  - [Forbidden to talk about it].

PMID- 25073307
TI  - [A cholera vaccine has proven its efficacy during an epidemic in Guinea].

PMID- 25073308
TI  - [Does a low PSA at 60 years old exclude the risk of developing prostate
      carcinoma?].

PMID- 25073309
TI  - [The astonishing story of the hospitalized Emir in a French public hospital].

PMID- 25073310
TI  - [Gratifications versus frustrations].

PMID- 25073311
TI  - [Diatoms in drowned and postmortem immersed rabbits' lungs].
AB  - OBJECTIVE: To investigate the numbers, sizes and types distribution of diatoms in
      drowned and postmortem immersed rabbits' lungs. METHODS: Sixty-two rabbits were
      randomly divided into drowning group (n = 30), postmortem immersion group (n =
      30) and land death group (n=2), and the diatoms in each lung lobe were analyzed
      quantitatively and qualitatively by microwave digestion and scanning electron
      microscopy. RESULTS: In the drowning group, the diatoms were detected in each
      lung lobe with Cyclotella and Melosira in the majority. In the postmortem
      immersion group, Cyclotella was in the majority. And the diatoms weren't detected
      in some lung lobes in postmortem immersion. There were significant differences in
      the detection rates of upper lobe of left lung, middle lobe and cardiac lobe of
      right lung in two groups (P < 0.05). CONCLUSION: Based on the microwave digestion
      and scanning electron microscopy, the numbers, sizes and types distribution of
      diatoms in drowned and postmortem immersed rabbits' lungs can be analyzed and
      used as references for testing theory.

PMID- 25073312
TI  - [Time-related expression of IL-6, IL-8 and TNF-alpha following explosive injury
      to rabbit's chest].
AB  - OBJECTIVE: To explore the relationship between the expression changes of
      cytokines, interleukin-6 (IL-6), interleukin-8(IL-8), and tumor necrosis factor
      alpha (TNF-alpha), and the wound time following explosive injury to rabbit's
      chest. METHODS: The rabbit's model of explosive injury was established. The
      expression levels of IL-6, IL-8 and TNF-alpha in the plasma were detected by
      ELISA method at different wound time (0.5-12h). RESULTS: The level of IL-6
      increased at 3h after wounding and reached peak at 6 h. The level of IL-8
      increased at 1 h and reached peak at 6 h. The level of TNF-alpha increased at 0.5
      h and reached peak at 3 h. CONCLUSION: IL-6, IL-8 and TNF-alpha have a time
      related expression after explosive injury.

PMID- 25073313
TI  - [Posture evoked response detecting in normal lower limb muscle and its
      influencing factors].
AB  - OBJECTIVE: To analyze the latency of posture evoked response of normal lower limb
      muscle in different stimulations and explore its influencing factors. METHODS:
      The normal lower limb was induced to produce postural evoked response by the
      dynamic posturography through two kinds of perturbations, the supporting surface
      rotation stimulation (Toes-up and Toes-down) and the horizontal perturbation
      stimulation (Forward and Backward). The latencies of tibialis anterior muscle and
      gastrocnemius muscle were recorded by surface electromyography acquisition
      system. The differences of the left and right limb, gender and height on the
      latency of postural evoked response were analyzed. RESULTS: (1) Under the Toes-up
      and Backward perturbation, the latency of tibialis anterior muscle was longer
      than gastrocnemius muscle; under the Toes-down and Forward perturbation, the
      latency of gastrocnemius muscle was longer than tibialis anterior muscle. (2) The
      latencies of left limb and right limb had no significant difference. (3) The
      latency in male was longer than that in female. (4) The latency gradually
      increased with the increase of height. CONCLUSION: In the postural evoked
      response, different perturbations, gender and height have significant impacts on
      the latency of posture evoked response of lower limb muscle. However, the effect
      of height and gender should be not considered referring to the same individual.

PMID- 25073314
TI  - [Relevance between writing characteristic and therapeutic effect in
      schizophrenia].
AB  - OBJECTIVE: To explore the relevance between writing characteristic and
      therapeutic effect in schizophrenia and to discuss the influence of aggressive
      behavior on writing characteristic. METHODS: Recoding the casual and fixed
      writing in admission, one week, two weeks, four weeks, eight weeks after
      treatment and rating Positive and Negative Syndrome Scale (PANSS) and Modified
      Overt Aggression Scale (MOAS). Choosing two characteristics, "relationship
      between font and grid lines" and "having big strokes or not", and comparing
      before and after treatment. RESULTS: Eight weeks after treatment, the score of
      PANSS decreased. The condition of patients and the writing characteristic
      improved as well. The differences of writing characteristics were statistically
      significant in patients with aggressive behavior before and after treatment (P <
      0.05). CONCLUSION: The writing characteristic has relation with therapeutic
      effects and improved with therapeutic effects in aggressive patients.

PMID- 25073315
TI  - [AS-PCR assay for 20 mtDNA SNP typing and haplotype frequency].
AB  - OBJECTIVE: To develop a multiplex allele-specific PCR (AS-PCR) assay with three
      color fluorescence labeling for mitochondrial DNA (mtDNA) SNP typing. METHODS:
      Based on the principle of AS-PCR, the primer sets were designed for 20 SNP
      located on the coding region of mtDNA and divided into 2 groups labeled with FAM
      and HEX fluorescence, respectively. A primer set included two forward (reverse)
      allelic specific primers with different sizes and a generic reverse (forward)
      primer. Blood samples from 200 unrelated individuals were analyzed by AS-PCR and
      capillary electrophoresis. Three random samples at least for each SNP site were
      examined and verified by direct sequencing. The haplotype frequency was
      investigated. RESULTS: Distinct electropherograms of 200 blood samples were
      obtained successfully. The typing results of direct sequencing were identical to
      those obtained from AS-PCR. The minimum detectable DNA concentration was 0.2 pg
      under the system of 10 microL. The sensitivity of the DNA concentrations ranged
      from 0.5 to 5 pg. The 200 individuals were assigned into 15 haplotype, and the
      haplotype diversity was 0.906 0. CONCLUSION: AS-PCR is a simple, rapid and
      efficient method for mtDNA SNP typing, and can be applied to forensic practice.

PMID- 25073316
TI  - [Development of an 18 X-InDel multiplex PCR system].
AB  - OBJECTIVE: To investigate Insertion/Deletion (InDel) polymorphism on the X
      chromosome and to screen 18 InDel loci for the Chinese Han population as a
      forensic DNA typing system auxiliary. METHODS: Eighteen X-InDel markers were
      selected using the Human Genome Browser and dbSNP database. Multiplex PCR primer
      pairs of selected X-InDel markers were designed using Primer 3 software and
      divided into 3 groups according to the amplified fragment length, labeled by FAM,
      HEX and TAMRA fluorescence dye, respectively. The population genetics research
      and comparative analysis of Chinese Han nationality and 4 main minorities, the
      Hui, Wei, Mongol, and Tibetan nationalities, were investigated with the system.
      RESULTS: A new multiplex genotyping system, named InDel X-18PLEX, was
      successfully developed and validated, consisted of 18 X-InDel markers on the X
      chromosome and 1 Amelogenin gender marker. No deviation from Hardy-Weinberg
      equilibrium expectations was detected in the distribution of genotypes in the 5
      investigated ethnic groups. However, there was significant difference between
      their distributions. From the investigation of Han nationality, high female
      (0.9999994) and male (0.999 88) overall discrimination power values were
      obtained, as well as high overall mean exclusion chance values in trios (0.999
      992) and in duos (0.99). CONCLUSION: InDel X-18PLEX meets the requirements as a
      forensic DNA complementary kit, providing effective supplementary analytical
      tools for difficult cases.

PMID- 25073317
TI  - [Cause of death related to medical disputes in Yancheng area: a study of 60
      autopsy cases].
AB  - OBJECTIVE: To summarize the pattern and main characteristics of fatal cases
      related to medical disputes in Yancheng area. METHODS: Sixty fatal cases of
      medical disputes were retrospectively analyzed to elucidate the annual incidence,
      characters of distribution of hospitals, gender and age of the decedents, types
      of diseases, and cause of death. RESULTS: Among 60 fatal cases, most cases
      happened in health clinics of county, township and village. There were more males
      than females. The major medical specialties involved included internal medicine,
      surgery, gynecology and pediatrics, with the internal medicine specialty having
      the highest incidence. CONCLUSION: Police institutions have advantages in
      investigation of these cases in their jurisdictions, which could enhance the
      ability of local medicolegal examination.

PMID- 25073318
TI  - [Sudden cardiac death of incarcerated prisoners: a study of 75 cases].
AB  - OBJECTIVE: To investigate the characteristics and influencing factors leading to
      sudden cardiac death (SCD) of incarcerated prisoners. METHODS: Seventy-five SCD
      cases of prisoners between 2000 and 2013 in Henan province were collected, and
      environment, psychological and physical factors were retrospectively analyzed.
      Combined with histopathological results, specific factors of SCD were also
      studied. RESULTS: In the 75 cases, 21 cases (28%) had definite chronic past
      medical histories, and 75 cases (100%) had cardiovascular disease confirmed by
      autopsy. CONCLUSION: Due to presence of the potential cardiac diseases, special
      incarcerated environment, psychological stress, and body-restraint might be the
      precipitating factors in SCD of those prisoners.

PMID- 25073319
TI  - [Distribution of diatoms in Chuanyang River of Pudong new area of Shanghai and
      its forensic application].
AB  - OBJECTIVE: To investigate the quantity and species distribution of diatoms in
      Chuanyang River of Pudong new area of Shanghai and provide references for the
      invesitigation of water body in forensic practice. METHODS: The water samples
      collected from 15 areas in Chuanyang River of Pudong new area in September 2012
      were examined by microscope to identify the species of diatoms. RESULTS:
      Cyclotella and Pinnularia were found to be the dominant species within the 12
      species of diatoms in Chuanyang River, which showed differences in species among
      the sections of Huangpu River, the center and the East China Sea. CONCLUSION: The
      differences in subsectional distribution of diatom species in Chuanyang River may
      provide a new foundation for forensic identification in drowning cases especially
      in the determination of falling location.

PMID- 25073320
TI  - [Biochemical indicators of anaphylactic shock and the application in forensic
      medicine].
AB  - Fatal anaphylactic shock is common in forensic practice. However, it is difficult
      to diagnose for lacking specific pathological and morphologic changes in forensic
      autopsy. The application of some biochemical indicators is of great significance.
      This paper reviews the biological characteristics of some biochemical indicators
      and detection methods. The forensic application, problems and prospects of these
      indicators are also introduced in details. The stable biochemical indicators,
      IgE, tryptase and chymase, show great potential and advantages in the
      identification of fatal anaphylactic shock in forensic medicine.

PMID- 25073321
TI  - [Epidemiological characters of Yunnan sudden death syndrome and its research
      progress].
AB  - Yunnan sudden death syndrome (YSDS) is an abruptly fatal disease of unknown
      etiology, found mostly in central or northwestern mountain area (with altitude
      between 1,815 and 2,225 meters) of Yunnan province from June to September every
      year. It occurs mostly in young female adults, with high incidences in Lisu, Yi
      and Miao ethnics and high familial aggregation. The clinical manifestation of
      YSDS is changeful and the pathological characteristic is lack of specificity. The
      pathogenesis may be attributed to several factors including poor hygiene and
      lower socioeconomic conditions, lack of Selenium or Chromium, infection of
      Coxsackie B virus, mushroom consumption and special geological conditions. This
      article reviews the epidemiologic features, clinical manifestations, pathological
      features, etiology and hypothesis in order to provide clues for the research of
      YSDS.

PMID- 25073322
TI  - Postmortem MSCT diagnosis of whiplash injuries in a traffic accident: a case
      report and review of the literature.
AB  - A 45-year-old male car driver died in a traffic accident of four cars rear-end
      collision on the highway. He was found to have died after a respiratory and
      cardiac arrest at the scene. No sign of skin injuries was observed from the
      external inspection. The autopsy was not permitted by the family members because
      of the local culture. Multislice computed tomography (MSCT) was applied to the
      current case, showing dislocation of C3-4 cervical vertebrae with II degree, C4
      vertebral plate fractures, and spinal stenosis. Post-mortem MSCT confirmed the
      diagnosis as whiplash injuries. MSCT was verified to be effective in showing the
      severity of whiplash injuries, thus providing certain objective evidence for
      medicolegal expertise.

PMID- 25073323
TI  - Tuberculous abdominal aortic aneurysm with alimentary tract hemorrhage: a case
      report with medico-legal implications.
AB  - An autopsy case of sudden death induced by alimentary tract hemorrhage was
      presented, which was caused by the unexpected rupture of clinically unrecognized
      tuberculous abdominal aortic aneurysm (TAAA). The initial diagnosis was made of
      the syndrome of coronary heart disease and hypertensive disease. The detailed
      autopsy showed that the alimentary tract hemorrhage was caused by a sudden
      rupture of the mass after posture changing was ascertained as the cause of death.
      The diagnosis of TAAA was determined by the autopsy findings. Analysis for the
      medical dispute of TAAA was described, and the difficulty of the diagnosis and
      medico-legal implications were also discussed.

PMID- 25073324
TI  - [Research presentation in the form of legal points].
AB  - What is the connection among scientific knowledge and public decision, at
      international, european and national level, in the field of biodiversity ? Firmly
      believing in the relevance of legal tools, we wanted to call into question the
      phenomenom of the massive externalization of scientific expertise in order,
      perhaps, to determine the conditions of a better guidance of the use of the
      latter. This article is presenting the results of a research witch have received
      the support of the "Fondation de Recherche pour la Biodiversite" (FRB).

PMID- 25073325
TI  - [Environmental protection: ethical and scientific sources of tension].
AB  - Environmental ethic is complex, dynamic, and related to cultural contexts that
      are neither given once and for all, nor valid for all people. Yet, the current
      biodiversity crisis tends to be followed by the spread of universal values
      related to nature and its protection. Far from standardizing the pluralism of
      these values, this universal trend leads to two major tensions in the field of
      nature conservation. The first concerns the scientific or epistemic values:
      nature or "biodiversity" is altogether being reduced in sub-categories or by
      contrast considered as a complex object by modern ecological science.
      Biodiversity is indeed both increasingly considered in terms of its complexity
      and unpredictability, or on the contrary, as a collection of natural objects that
      can and must be managed with easily quantifiable indicators. The second tension
      concerns ethical values. These values tend to be reduced and simplified in
      equating nature with "services" that can benefit human societies. But this
      utilitarian reduction also hides a diversification of ethical values. This
      article aims to analyze what characterizes this contemporary ethical and
      scientific floating with respect to the values involved in the protection of
      nature.

PMID- 25073326
TI  - [Biodiversity and civil liability: the role of assessment].
AB  - The purpose of this paper is to make the link between expertise and biodiversity
      through the civil liability Law. Indeed, since Erika Case (Cour de Cassation,
      Crim. 25 septembre 2012), this Law recognised the ecological damage. This one is
      defined as an damage caused to Nature and especially Biodiversity. Thus, the
      expertise has to play a major role. In this paper, two roles are studied: first
      all all, the expertise allows to assess the damage of Biodiversity itself, to
      define and to prove it. Secondly, the expertise is an instrument which is very
      important for prescribing the measures of compensation, in kind or pecuniary
      compensation.

PMID- 25073327
TI  - [The intergovernmental science-policy platform on biodiversity and ecosystem
      services (IPBES)].
AB  - Filling an identified gap, the establishment of an international mechanism for
      science/policy and expert/decision maker interface, in the field of biodiversity
      does not go so smoothly. This new institution is the result of a relatively long
      and arduous international negotiations process, the starting point having been an
      idea launched in Paris in 2005 at an international conference on biodiversity and
      supported by President Chirac. The "Intergovernmental Science-Policy Platform on
      Biodiversity and Ecosystem Services" (IPBES) is part of a legal and institutional
      landscape very complex and fragmented. Even though it was officially established
      in 2012 and held its first meeting in January 2013, its status and governance, as
      well as its procedures and methods of operation remain to be defined. Often
      presented as the IPCC (Intergovernmental Panel on Climate Change) biodiversity,
      it is inspired in fact by the latter while distinguishing in several respects.

PMID- 25073328
TI  - [The treatment of scientific knowledge in the framework of CITES].
AB  - Access to scientific knowledge in the context of CITES is a crucial issue. The
      effectiveness of the text is indeed largely based on adequate scientific
      knowledge of CITES species. This is a major challenge: more than 30,000 species
      and 178 member states are involved. The issue of expertise, however, is not
      really addressed by the Convention. The question was left to the consideration of
      the COP. Therefore, the COP has created two ad hoc scientific committees: the
      Plants Committee and the Animals Committee, conferring upon them an ambitious
      mandate. The article addresses some important issues at stake which are linked to
      institutional questions, as well as the mixed record after twenty-five years of
      practice.

PMID- 25073329
TI  - [The scientific expert in the example of regional fishery management councils: a
      multi-faceted player in the decision-making process].
AB  - The management and conservation of fish stocks require precise scientific
      knowledge, especially on the state of said stocks and their capacity for renewal.
      For instance, the setting of fishing "quotas", which consists in the
      determination of the quantity of fish that can be taken in a given period, cannot
      be done at random since these allocations represent environmental and economic
      stakes. Thus, decision makers logically call upon experts to adopt informed
      decisions. Consequently, various regional fisheries Commissions created
      Scientific Committees, which were associated to their work to have available
      knowledge on a permanent basis. And yet, the institutionalisation of scientific
      expertise within regional fisheries Commissions led the expert to go beyond its
      traditional role of knowledge provider. Facing his usual context of scientific
      uncertainty, the expert has indeed acquired other responsibilities. Through this
      "micro-legal" study--in the sense that it results from an empirical analysis of
      the Mediterranean context--we will try to highlight the different functions of
      the expert associated with the decision process in the field of the management
      and protection of Mediterranean fish stocks.

PMID- 25073330
TI  - [The role of civil society in constructing scientific questions: focus on the
      work of the CESTM at the Aquarium La Rochelle].
AB  - The relation between experts and civil society raises profound questioning. The
      first of them is the role of civil society in their evaluation work and in their
      research. We note that the involvement of citizen leds not only to build
      scientifical questions, but also to enrich and to answer them. In that way, civil
      society becomes a key player and an irreplaceable actor of the scientific
      research. This article highlights action carry out by the Centre d'Etudes et de
      Soins pour les Tortues Marines of the Aquarium La Rochelle which asks civil
      society to help it everydays to fulfill his duties. At the end of a training
      period, or thanks to a spontaneous initiative, volunteers get involve to move
      research.

PMID- 25073331
TI  - [Expertise and biodiversity: the environmental impact assessment in the context
      of Natura 2000 network].
AB  - Natura 2000 network, established by the Habitats directive, states that "any plan
      or project likely to have a significant effect on a Natura 2000 site, shall
      undergo an appropriate assessment to determine its implications for the site".
      The safeguards set out in this article are triggered not by a certainty but by a
      likelihood of significant effects. The paradox clearly appears: the significant
      implications of a project can be assessed only through an impact assessment
      process. So the administration and the judge are asked, inevitably, to
      participate to the building of the definition of practical aspect of expertise.

PMID- 25073332
TI  - [Harmonization of national and foreign sanitary laws on industrial aerosols].
AB  - According to existing hygienic norms in Russian Federation, dust control covers a
      whole mass of particles contained in air of workplace--that is based on biologic
      value of all mass of dust affecting human, rather than of separate dust
      fractions, as is accepted abroad. State Standard specification R 54578-2011
      establishes general principles of hygienic regulation, control and evaluation of
      occupational diseases risk due to aerosols with predominantly fibrogenous effects
      through measuring mass concentration of all dust particles contained in air of
      workplace, rather than groundless selective isolation of its separate fractions.
      The standard is set for specifying technical regulations in extracting branches,
      processing industry, machinery, technologic processes with dust releases.

PMID- 25073333
TI  - [Structure and dynamics of occupational lung diseases in workers of Moscow region
      under longstanding 50 years of observation].
AB  - The article covers data on occupational morbidity in Moscow region over last 50
      years. Stable number of newly diagnosed occupational diseases was seen up to
      first half of 1990s. Afterwards, steady decrease in occupational morbidity is
      seen with closure of major industrial enterprises. Among occupational pulmonary
      diseases, dust fibrosis (pneumoconiosis--44%) prevail. Tuberculosis complication
      of silicosis decreased, additional general somatic concomitants (arterial
      hypertension, ischemic heart disease, malignancies) are more frequent. Prevalence
      of occupational bronchial asthma has increased 16 times vs. that in 1976.

PMID- 25073334
TI  - [Contemporary features of pneumoconiosis formation and course in miners of East
      Donbass].
AB  - The author analyzed dynamics and structure of occupational morbidity including
      pneumoconiosis in Rostov region of Russian Federation, since 1990 until now. They
      were compared with analogous parameters of previous historical period. Findings
      are that contemporary dynamics of anthracosilicosis clinical features is
      characterized by severily reduced terms of the disease development from medical
      registration of the diseased miner, earlier addition of malignancy, respiratory
      failure and other complications--that in aggregate causes earlier disablement and
      drastically reduced survival rate in occupational patients with
      anthracosilicosis.

PMID- 25073335
TI  - [Clinical morphology of hypersensitivity pneumonitis].
AB  - The article presents a viewpoint on morphogenesis types of dust pulmonary
      diseases and details clinical morphology of hypersensitivity pneumonitis, based
      on lung biopsy studies in industrial workers.

PMID- 25073336
TI  - [Analysis of ambient air suspensions in Karakan coalfield in Kouzbass].
AB  - The article covers results of studies concerning nano- and microparticles in
      atmospheric suspensions in snow collected in 11 points of Karakan coal extraction
      cluster (Kouzbass) in winter of 2011-2012. As a reference, a sample was taken on
      territory of Kouzbass botanical garden of Human Ecology Institute with RASc
      Siberian Division. All the points studied appeared to be polluted with
      technogenous suspensions--that proves high ecologic load on atmosphere over all
      territory of Kouzbass coalfield. Particles found in snow could be placed in
      decrement order: coal (up to 80%), natural minerals (mostly aluminosilicate and
      quartz) (up to 10%), vegetable detrital matter, unidentifiable technogenic
      particles, metals and their compounds (mostly Fe, Ba and Ti). Some areas appeared
      to frequently present microparticles containing rare-earth metals (rare-earth
      phosphates and alumophosphates prevail).

PMID- 25073337
TI  - [Evaluation of social demographic aspect of life quality of coal extraction
      workers in Kouzbass enterprises].
AB  - For assessing influence of social factors on life quality of workers in coal
      extraction enterpirses of Kemerovo region, the authors used questionnaire SF-36.
      Life quality parameters of workers engaged into coal extraction in Kemerovo
      region appeared to lower with age from 20 to 64 years. Life quality parameters on
      scales of pain, physical functioning and general health are invertedly correlated
      with age and length of service in hazardous work conditions for coal extraction
      workers. Life quality of the miners is influenced by the following factors:
      marital status, educational level and income level of the workers.

PMID- 25073338
TI  - [Life quality in individuals having occupational diseases caused by various
      occupational factors].
AB  - The article presents main results of studies concerning life quality in
      individuals having chronic occupational diseases of important social value. Life
      quality in patients with chronic mercurial intoxication and dust bronchitis
      appeared to result from personal, social and psychologic features.

PMID- 25073339
TI  - [Features of subjective evaluation of life quality in individuals having
      occupational diseases].
AB  - The article covers main results of study concerning life quality in patients with
      vibration disease and neurosensory deafness. The authors analyzed psychologic
      types of attitude to the disease, assessed physical, psychologic and social state
      in patients with occupational diseases, determined role of psychologic component
      in treatment of such patients.

PMID- 25073340
TI  - [Forming a concept of pharmaceutic aid in occupational diseases].
AB  - The review covers aspects connected with formation of concept of pharmaceutic aid
      in occupational diseases. The authors emphasize problems of interactions between
      pharmacy workers and medical organizations officers for optimizing pharmaceutic
      aid. Prospects of the pharmaceutic aid concept implementation into treatment of
      specific diseases including occupational diseases in miners are shown.

PMID- 25073341
TI  - [Methodologic approaches to farmacologic economic analysis of actual inpatient
      treatment of occupational diseases].
AB  - To improve miners' health nowadays, effective application of available means and
      implication of economic management methods are necessary, as quality medical and
      pharmaceutic care for miners requires significant financial, material and working
      efforts both from the government and from every institution operating in health
      care.

PMID- 25073342
TI  - [Features of hemostasis system and vascular epithelium growth factor in arterial
      hypertension with high occupational risk].
AB  - Study covered vascular, platelet, coagulation and fibrinolytic parts of
      hemostasis and vascular endothelial growth factor in individuals with arterial
      hypertension in various occupational groups.

PMID- 25073343
TI  - [Features of systemic hemostasis in arterial hypertension with vibration disease
      in accordance with vibration type].
AB  - Study covered systemic hemostasis in 69 males aged 47.6 +/- 2.1 years with 1
      stage arterial hypertension and 1 stage vibration disease, exposed to various
      types of occupational vibration at work. Those exposed to bump vibration
      demonstrated an increase in platelets aggregation with all aggregation inductors,
      if compared to reference values, increased generaton and activity of von
      Willebrand factor, moderately depressed fibrinolysis system with increased serum
      content of fibrin and fibrinogen degradation products and decreased
      anticoagulation factors activity. Those exposed to rotation vibration
      demonstrated less changes.

PMID- 25073344
TI  - [Optimizing a system of medical rehabilitation for vibration disease patients].
AB  - The study was aimed to reveal efficiency of extracorporeal shock-wave therapy in
      complex treatment of vibration disease patients. Examination covered 92 patients
      with varying severity of vibration disease, 58 of which received extracorporeal
      shock-wave therapy with Piezo Wave device produced by Richard Wolf in addition to
      traditional treatment. The treatment efficiency was evaluated through its
      influence on intensity and regression of pain syndrome. Comparative analysis
      showed that extracorporeal shockwave therapy in the treatment complex
      considerably increases efficiency and leads to earlier and more stable regression
      of pain in distal parts of hands. Two variants of chronic pain response to
      extracorporeal shock-wave therapy were revealed. Marked analgetic potential, good
      tolerance and stability of the results obtained enable to recommend
      extracorporeal shock-wave therapy in rehabilitation complex for vibration disease
      patients.

PMID- 25073345
TI  - [Contemporary approaches in evaluation of pro- and antioxidant status in combined
      forms of occupational diseases due to functional overstrain].
AB  - Complex evaluation covered parameters pro- and antioxidant system in some somatic
      diseases, mostly in arthrosis and polyneuropathies due to occupational factor of
      functional overstrain. The results obtained prove influence of prolonged
      occupational functional overstrain causing excessive free oxidative radicals
      formation, strain of antioxidant status and subsequent oxidant stress--that is
      clinically manifested with "mutual burden" syndrome in combined occupational
      diseases.

PMID- 25073346
TI  - [Features of changes in joints structure, in lipid spectrum and vascular
      remodelling with occupational arthrosis].
AB  - Studies covered features of intraarticular cartilage and soft tissue components
      of knee joints, lipid spectrum and structures of peripheral arteries in
      occupational knee osteoarthrosis. Findings are relationships between lipid
      metabolism disorders and frequency of cartilage degeneration in knee joints, with
      vascular remodelling parameters.

PMID- 25073347
TI  - [Mobilization and traction therapy for lumbar dorsopathies in obese individuals
      working in sedentary conditions].
AB  - Obese individuals working in sedentary conditions, if having neurologic symptoms
      in lumbar dorsopathies, when subjected to mobilization and traction therapy in
      rehabilitation complex, demonstrated less pain, increased spine mobility and
      prospective observations proved longer clinical remission, if compared to
      standard treatment.

PMID- 25073348
TI  - [Some aspects of cognitive functions in chronic intoxication by organic
      solvents].
AB  - Study covered 20 females with chronic intoxication with organic solvents, who
      worked long as painters on industrial enterprise. To reveal clinically
      significant cognitive disorders, Mini-Cog scale was applied. Drawing test helped
      to reveal visual and spatial disorders, restults were expressed in scores. Memory
      was evaluated through methods "operative memory", "short-term memory", "memory
      for figures", "memory for images", "hearing memory"--that proved lower results in
      the main group of examinees. In 75% of patients with occupational diseases caused
      by organic solvents, moderate cognitive disorders of amnestic multifunctional
      type were seen. 100% of individuals having chronic intoxication with organic
      solvents demonstrated encephalopathy. In comparison with reference group, the
      main group members had more frequent 1 and 2 degrees encephalopahy.

PMID- 25073349
TI  - [Role of genetic factors in development of occupational obstructive lung
      disease].
AB  - The authors represent associative study of 180 patients having chronic
      obstructive lung disease 1-2 stages, who exposed at work to industrial pollutants
      (58.3% exposed to moderately fibrogenous dust and 41.7%--to a complex of aromatic
      organic solvents). Findings are increased (p < 0.05) concentration of IL-1beta in
      individuals exposed to chemicals, when compared to those exposed to dust at work.
      Relation was seen between transforming growth factor beta1 (rs1804470 of TGFB1
      gene) and rs1828591 of HHIP gene with propensity to COLD formation. Genotype AA
      and AG demonstrated protective effect against the disease.

PMID- 25073350
TI  - [Genetic aspects of occupational chronic obstructive lung disease under exposure
      to various risk factors].
AB  - The article deals with data on association of SNP rs1828591 of HHIP gene with
      COLD development under exposure to dust and chemical factors. SNP rs1800470 of
      TGFbeta1 gene is associated with occupational COLD under exposure to dust and did
      not show connection with COLD under exposure to chemical aerosols. No association
      was seen between SNP rs4129267 of IL-6R gene and SNP rs1051730 of CHRNA3 gene
      with occupational COLD under exposure to the studied factors. SNP rs1828591 of
      HHIP gene is associated with occupational COLD development under exposure to dust
      and chemical factors. Study of association of genotype and phenotypic features of
      COLD revealed the following trends: "dust" COLD patients with genotype AA SNP
      rs1800470 of TGFbeta1 gene show lower level of C-reactive protein and TNF-alpha,
      if compared with other genotypes.

PMID- 25073351
TI  - [Evaluating diagnostic efficiency of vascular wall diseases via sphygmomanometry
      method].
AB  - The article covers study of 100 patients, supporting diagnostic efficiency of
      vascular wall pathology via sphygmomanometry in various age groups with various
      diseases.

PMID- 25073352
TI  - [Biomedical engineering research at St Petersburg State Electrotechnical
      University].

PMID- 25073353
TI  - [The effect of X-ray tube focal spot size on radiovisiograph resolution].

PMID- 25073354
TI  - [Three-dimensional scanning systems based on binocular stereovision for medical].

PMID- 25073355
TI  - [Method and system for non-occlusion monitoring of human blood pressure].

PMID- 25073357
TI  - [Remote monitoring system for diabetes patients].

PMID- 25073356
TI  - [Technology and system for the noninvasive spectrophotometric assessment of
      hematocrit level].

PMID- 25073358
TI  - [Microfocus X-ray tube with rotating anode].

PMID- 25073359
TI  - [Computerized plantography and podometry as screening evaluation method of
      anatomic and functional disorders of feet].

PMID- 25073360
TI  - [Information system for surgical emergency units with computer tomogram
      processing module].

PMID- 25073361
TI  - [Systemic analysis of regional dispensarization data].

PMID- 25073362
TI  - [Portable equipment for monitoring of human adaptation to changes in
      environmental conditions].

PMID- 25073363
TI  - [A portable device for monitoring human adaptation to changing environmental
      conditions].

PMID- 25073365
TI  - [Instrumental and methodological support for the musculoskeletal system imbalance
      research].

PMID- 25073366
TI  - [Web technologies to support decision-making by physician].

PMID- 25073367
TI  - [Systems biology of amino acids].

PMID- 25073368
TI  - [OMICS in the research of the function and safety of amino acids].

PMID- 25073369
TI  - [Autophagy regulation by amino acids].

PMID- 25073370
TI  - [Amino acid metabolism in cancer cells].

PMID- 25073371
TI  - [Amino acid transporters in cancer].

PMID- 25073372
TI  - [The regulatory function of isoleucine in glucose metabolism and its clinical
      application].

PMID- 25073373
TI  - [The role of L-arginine and L-citrulline on atherosclerosis].

PMID- 25073374
TI  - [Lipid metabolism and glutamine].

PMID- 25073375
TI  - [Skeletal muscle atrophy and amino acidskeletal muscle atrophy and amino acid].

PMID- 25073376
TI  - [Essentiality of de novo L-serine synthesis for embryonic development and higher
      functions].

PMID- 25073377
TI  - [Galactose-containing carbohydrates in the inflammation, development and nervous
      system].

PMID- 25073378
TI  - [Mechanism of RNA polymerization by Qbeta replicase].

PMID- 25073379
TI  - [Molecular basis of tRNA dihydrouridine synthase].

PMID- 25073380
TI  - [A role for cFLIP in maintaining tissue homeostasis].

PMID- 25073381
TI  - [The physiological role of exogenous sterol uptake in yeast].

PMID- 25073382
TI  - [Zinc homeostasis and zinc signaling thoughts from plant zinc transporters].

PMID- 25073383
TI  - [The rate of synaptic vesicle filling with neurotransmitter glutamate].

PMID- 25073384
TI  - Acronyms, not acrimony.

PMID- 25073385
TI  - Ethics and old age.

PMID- 25073387
TI  - Cone-beam computed tomography is the imaging technique of choice for
      comprehensive orthodontic assessment.

PMID- 25073386
TI  - Orthodontics 2014 at the U of M School of Dentistry.

PMID- 25073388
TI  - Lyme disease.

PMID- 25073390
TI  - Dentistry and depression.

PMID- 25073391
TI  - Perspective, perfection, and a gracious acceptance.

PMID- 25073392
TI  - Oleanolic acid synthetic oligoglycosides: a review on recent progress in
      biological activities.
AB  - The natural product oleanolic acid has been widely used for treating hepatopathy
      in China, whereas its clinical application was confined by poor solubility in
      water. Inspired by remarkable bioactivities and physical properties of
      triterpenoid saponins, synthesis and biological evaluation of oleanolic acid
      oligoglycosides drew considerable attention. In the past several years, chemical
      efforts were made toward glycosylated modifications of oleanolic acid at C3-OH
      and C17-COOH, of the carbons at ring A/C, and of the functional groups of
      oleanolic acid lactone. To provide useful information for further study and
      applications of oleanolic acid derivatives, a total of 177 oleanolic acid
      synthetic oligoglycosides and their bioactivities (e.g., antiosteoporosis,
      antidiabetes, antibacterial, anticancer and hemolytic effects) were reviewed;
      structure-activity relationships and promising agents are indicated.

PMID- 25073393
TI  - Racemic synthesis and solid phase peptide synthesis application of the chimeric
      valine/leucine derivative 2-amino-3,3,4-trimethyl-pentanoic acid.
AB  - The synthesis of non natural amino acid 2-amino-3,3,4-trimethyl-pentanoic acid
      (Ipv) ready for solid phase peptide synthesis has been developed. Copper (I)
      chloride Michael addition, followed by a Curtius rearrangement are the key steps
      for the lpv synthesis. The racemic valine/leucine chimeric amino acid was then
      successfully inserted in position 5 of neuropeptide S (NPS) and the
      diastereomeric mixture separated by reverse phase HPLC. The two diastereomeric
      NPS derivatives were tested for intracellular calcium mobilization using HEK293
      cells stably expressing the mouse NPS receptor where they behaved as partial
      agonist and pure antagonist.

PMID- 25073394
TI  - Rapid and simplified HPLC-UV method with on-line wavelengths switching for
      determination of capecitabine in human plasma.
AB  - Capecitabine is an important oral fluoropyrimidine anticancer drug. The purpose
      of this study was to overcome limitations of previously reported methods and
      propose an optimized and widely available tool for analysis of capecitabine in
      human plasma. The simplification of the liquid-liquid extraction procedure
      involved elimination of unnecessary addition of phosphoric acid and reduction of
      the extraction solvent volume. The use of voriconazole as the internal standard,
      combined with gradient elution and on-line wavelength switching, assured very
      high within- and between-run precision of results (relative standard deviation <
      7.1% for lower limit of quantification) and enabled the reduction of the total
      chromatographic run time to 8 min. The calibration curve was linear within the
      range of 0.05-10.00 microg/mL and the method selectivity was confirmed in the
      presence of capecitabine metabolites. All validation parameters met the
      acceptance criteria set by international regulatory guidances, which proves that
      the method leads to reliable results. The method may be applied in human
      pharmacokinetic studies, for the regulatory purposes and therapeutic drug
      monitoring.

PMID- 25073395
TI  - Assay of 6-gingerol in CO2 supercritical fluid extracts of ginger and evaluation
      of its sustained release from a transdermal delivery system across rat skin.
AB  - Ginger has been widely used as healthy food condiment as well as traditional
      Chinese medicine since antiquity. Multiple potentials of ginger for treatment of
      various ailments have been revealed. However, the biological half-life of 6
      gingerol (a principal pungent ingredient of ginger) is only 7.23 minutes while
      taken orally. Delivery of ginger compositions by routes other than oral have
      scarcely been reported. Therefore, we studied a noninvasive transdermal drug
      delivery system (TDDS) of ginger to bypass hepatic first pass metabolism, avoid
      gastrointestinal degradation and achieve long persistent release of effective
      compositions. After establishment of a HPLC analysis method of 6-gingerol, assays
      of 6-gingerol were performed to compare two kinds of ginger extracts. Then, the
      characteristics of transdermal delivery of 6-gingerol in TDDS were exhibited. The
      results showed that the contents of 6-gingerol in two kinds of ginger extracts
      were significantly different. The maximal delivery percentage of 6-gingerol
      across rat skin at 20 h was more than 40% in different TDDS formulations. TDDS
      may provide long-lasting delivery of ginger compounds.

PMID- 25073396
TI  - Development of a novel triamcinolone acetonide-loaded spray solution for the
      treatment of stomatitis.
AB  - To develop a novel triamcinolone acetonide (TAA)-loaded spray for the treatment
      of stomatitis, several spray solutions were prepared using various amounts of
      TAA, Eudragit L100 (Eudragit L) and PEG 400, and 100 ml ethanol. Their viscosity
      and spraying potential were investigated, with the result that the spraying
      threshold was 9.5 cP. The effect of PEG 400 on the properties of films formed
      after spraying was assessed. Its anti-inflammatory effect in mice was evaluated
      and compared to a commercial product. As the PEG 400 concentration increased, the
      film elongation and washability by the saliva solution increased, and tensile
      strength decreased. PEG 400 had little effect on mucoadhesive force and drug
      release. The TAA-loaded spray solution containing TAA, Eudragit L, PEG 400 and
      ethanol at the ratio of 1:6:3:100 (w/w/w/v) was easy to spray onto stomatitis
      lesions in the mouth via a spraying vessel incorporating a long straw. After
      spraying, the TAA-loaded spray formed a film with suitable elongation, tensile
      strength and washability that attached onto the mucosal membrane and released the
      drug. Moreover, it had excellent anti-inflammatory properties, similar to those
      of the commercial product. Thus, this novel TAA-loaded spray solution was easy to
      administer, had good film properties and excellent anti-inflammatory efficacy,
      and is therefore a potential candidate for the treatment of stomatitis.

PMID- 25073397
TI  - Arylsulfatase A bound to poly(butyl cyanoacrylate) nanoparticles for enzyme
      replacement therapy--physicochemical evaluation.
AB  - Arylsulfatase A (ASA) deficiency is the cause of metachromatic leucodystrophy
      (MLD), a lysosomal storage disease associated with severe neurological disorders.
      Poly(butyl cyanoacrylate) (PBCA) nanoparticles overcoated with polysorbate 80
      enabled the delivery of several drugs across the blood-brain barrier to the brain
      suggesting that these nanoparticles also may transport ASA across this barrier.
      The objective of this research, therefore, was to evaluate the feasibility of
      loading ASA onto PBCA nanoparticles. A stable ASA-loaded PBCA nanoparticle
      formulation was developed that could be easily freeze-dried and stored over a
      period of more than 8 weeks. The maximum loading capacity for this enzyme was -59
      microg per 1 mg of PBCA. In the presence of 3% sucrose as a lyoprotector the
      activity of freeze-dried ASA was found to be 100% recoverable.

PMID- 25073398
TI  - Intracellular trafficking mechanism of cationic phospholipids including cationic
      liposomes in HeLa cells.
AB  - The development of gene delivery methods is essential for the achievement of
      effective gene therapy. Elucidation of the intracellular transfer mechanism for
      cationic carriers is in progress, but there are few reports regarding the
      intracellular trafficking processes of the cationic phospholipids taken up into
      cells. In the present work, the trafficking processes of a cationic phospholipid
      (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) were investigated from
      intracellular uptake to extracellular efflux using cationic liposomes in vitro.
      Following intracellular transport of liposomes via endocytosis, DOTAP was
      localized in the endoplasmic reticulum, Golgi apparatus, and mitochondria.
      Moreover, the proteins involved in DOTAP intracellular trafficking and
      extracellular efflux were identified. In addition, helper lipids of cationic
      liposomes were found to partially affect this intracellulartrafficking. These
      findings might provide valuable information for designing cationic carriers and
      avoiding unexpected toxic side effects derived from cationic liposomal
      components.

PMID- 25073399
TI  - Induction of human CYP3A4 by huperzine A, ligustrazine and oridonin through
      pregnane X receptor-mediated pathways.
AB  - The pregnane X receptor (PXR) is a key regulator of CYP3A4, which is involved in
      catalyzing the metabolic conversion of a number of endogenous substrates. In this
      study, we screened 22 compounds isolated from traditional Chinese herbal
      medicines using luciferase reporter gene assays for inspecting their capabilities
      in inducing PXR-mediated transactivation of CYP3A4 expression. In addition, the
      mRNA and protein expressions of CYP3A4 and PXR as well as the enzymatic activites
      of CYP3A4 were analyzed by real-time PCR, Western blot analysis and UPLC-MS/MS
      based metabolite assay in LS174T cells. Huperzine A, ligustrazine and oridonin
      were identified to be the inducers of CYP3A4. These compounds induced the CYP3A4
      reporter luciferase activity, and up-regulated CYP3A4 mRNA and protein levels
      significantly. Besides, huperzine A, ligustrazine and oridonin significantly up
      regulated enzymatic activities of CYP3A4. However, the three compounds showed no
      effects on PXR mRNA and protein expression. To our knowledge, it is the first
      identification of these three compounds as PXR activators to induce CYP3A4. These
      results indicate that huperzine A, ligustrazine and oridonin induced CYP3A4
      expression and activation via PXR dependent pathways, and might contribute to
      drug-drug interactions.

PMID- 25073400
TI  - In vivo effects of scutellarin on the activities of CYP1A2, CYP2C11, CYP2D1, and
      CYP3A1/2 by cocktail probe drugs in rats.
AB  - OBJECTIVE: To investigate the influence of scutellarin on the activities of
      CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 in rats in vivo. METHODS: Scutellarin and
      saline were intravenously administered to male Wistar rats via the caudal vein
      for 7 days consecutively. On the 8th day, the rats were treated with probe drugs
      of caffeine (10 mg/kg), tolbutamide (10 mg/kg), metoprolol (20 mg/kg), dapsone
      (10 mg/kg) by intraperitoneal injection, and the blood samples were collected at
      different times. The probe drugs in the blood samples were measured by ultra
      performance liquid chromatography mass spectrometer (UPLC-MS/MS) and the changes
      of the pharmacokinetics parameters of the drugs were observed to evaluate the
      effects of scutellarin on the four CYP450 isoforms in rats. RESULTS: The activity
      of CYP1A2 in rats was inhibited significantly after treatment with scutellarin by
      increased caffeine t1/2 (21.76%, P < 0.05), T(max) (43.05%, P < 0.05), C(max)
      (43.92%, P < 0.01) and AUC(0-infinity) (50.88%, P < 0.01) in the scutellarin
      treated group compared with those of the blank control. The activity of CYP2C11
      in rats was inhibited significantly after treatment with scutellarin by increased
      tolbutamide t1/2 (16.74%, P < 0.01), T(max) (116.87%, P < 0.05), C(max) (63.78%,
      P < 0.01) and AUC(0-infinity) (70.61%, P < 0.01) in the scutellarin-treated group
      compared with those of the blank control. The activity of CYP3A1/2 in rats was
      inhibited significantly after treatment with scutellarin by increased dapsone
      t1/2 (45.28%, P < 0.05), T(max) (81.55%, P < 0.05), C(max) (155.58%, P < 0.01)and
      AUC(0-infinity) (176.35%, P < 0.01) in the scutellarin-treated group compared
      with those of the blank control. The pharmacokinetic parameters of metoprolol
      were not significantly changed in the scutellarin-treated group compared with
      those of the blank control. CONCLUSION: Scutellarin could significantly inhibit
      CYP1A2, CYP2C11 and CYP3A1/2 activities in rats in vivo, but had no effects on
      the activity of CYP2D1.

PMID- 25073401
TI  - The selective ASIC3 inhibitor APETx2 alleviates gastric mucosal lesion in the
      rat.
AB  - This study aimed to assess the in vivo efficacy of acid sensing ion channel 3
      (ASIC3) inhibitor APETx2 to alleviate acute gastric mucosal lesion (AGML) in a
      rat model. Thirty-six male Wistar rats were divided randomly into three groups:
      control group, water immersion restraint stress (WIRS) group, and APETx2
      treatment group (n = 12). AGML was induced by WIRS for 6 h, and 25 microg/kg
      APETx2 was injected intraperitoneally before the onset of stress. Intragastric
      pH, ulcer index (UI) and gastric histopathological changes were measured, ASIC3
      expression in thoracic dorsal root ganglia (DRG) neurons was examined by
      immunohistochemistry, PCR and Western blot analysis. Compared with control group,
      WIRS group showed obvious gastric injury with increased UI score, decreased
      intragastric pH and increased ASIC3 expression in DRG neurons (p < 0.05). APETx2
      treatment before WIRS significantly alleviated gastric mucosal injury, decreased
      UI score, decreased gastric acidity and reduced ASIC3 expression in thoracic DRG
      neurons (p < 0.05). In conclusion, ASIC3 expression in DRG neurons projecting to
      the stomach is positively correlated with gastric mucosal lesion and acidosis in
      WIRS model. ASIC3 inhibitor APETx2 could improve gastric acidosis and alleviate
      AGML.

PMID- 25073402
TI  - Adenovirus vector-mediated herpes simplex virus-thymidine kinase gene/ganciclovir
      system exhibits anti-tumor effects in an orthotopic hepatocellular carcinoma
      model.
AB  - Adenovirus vector-mediated herpes simplex virus-thymidine kinase/ganciclovir
      (ADV.tk/GCV) system is a promising approach for cancer gene therapy. This study
      aimed to investigate the anti-tumor efficacy and the underlying mechanisms of
      ADV.tk/GCV system in orthotopic hepatocellular carcinoma (HCC) model. A total of
      132 female nude mice orthotopic HCC models were established and tumors were
      directly injected with ADV.tk (5.0 x 10(6) vector particles/kg) or saline
      solution, 24 h later the animals were intraperitoneally administrated by
      ganciclovir (30 mg/kg) or saline solution for 7 consecutive days. We observed
      that ADV.tk/GCV resulted in a significant regression of tumor growth and a
      significant prolongation of survival of the mice. At each given time point, the
      percentages of cleaved caspae-3, caspase-9 and TUNEL positive cells were
      significantly higher in the ADV.tk + GCV group than saline group (P < 0.005),
      while CD31 and VEGF staining were significantly less in ADV.tk + GCV group than
      in saline group (P < 0.005). In summary, ADV.tk/GCV system exhibits dramatic anti
      tumor effects in orthotopic hepatocellular carcinoma model by promoting apoptosis
      and inhibiting angiogenesis, and is a promising treatment strategy for hepatic
      carcinoma.

PMID- 25073403
TI  - Population pharmacokinetics of intravenous levofloxacin 500 mg/day dosage in
      infected patients.
AB  - The purpose of this study was to explore the population pharmacokinetic features
      of levofloxacin in Chinese infected patients. A total of 27 Chinese adult
      infected patients were treated with intravenous levofloxacin (500 mg/day). In
      total, 49 plasma samples of levofloxacin were collected immediately after
      intravenous dripping and before administration on the 3rd, 4th or 5th day. A
      nonlinear mixed effect model was used to model the population pharmacokinetic
      (PK) behavior of levofloxacin. The final population pharmacokinetic models were
      validated using the bootstrap method. Some covariates, including demographic
      characteristics and hematological and biological indicators, were analyzed. A
      structural model was developed based on a one-compartment model with intravenous
      infusion and first-order elimination. The typical population values for
      pharmacokinetic parameters of apparent clearance (CL) and apparent distribution
      volume (V) were 5.84 L/h and 43.3L, respectively. The inter-individual
      variabilities of CL and V were 7.75% and 6.4%, respectively, while the intra
      individual variability of observed concentrations was 0.06 microg/mL. The
      covariates of age and AST influenced the CL and V values determined by the final
      model. The present study developed population pharmacokinetic models for
      levofloxacin in infected Chinese patients. The results detailed here could
      provide a reference for individualized levofloxacin therapy in the clinical
      setting.

PMID- 25073404
TI  - Long-term use of ciclosporin on kidney transplant recipients surviving more than
      10 years.
AB  - OBJECTIVE: To evaluate the long-term use of ciclosporin on kidney transplant
      recipients who survived more than 10 years. METHODS: We reviewed cadaveric kidney
      transplant patients who had survived 10 years or longer in this study. Patients
      were divided into five groups based on their ciclosporin concentration at one
      year: group 1 (> 250 ng/ml), group 2 (200-250 ng/ml), group 3 (150-200 ng/ml),
      group 4 100-150 ng/ml) and group 5 (< 100 ng/ml). Lab parameters were compared
      among these groups over time. RESULTS: There were no differences in lab
      parameters among the five groups. At five years, systolic blood pressures (SBP),
      TG, CH, DB, TB were significantly higher in groups 3, 4, and 5. Uric acid was
      also higher but albumin was lower in group 5 compared to those in all other
      groups. Prevalence of proteinuria in both groups 4 and 5 were lower. At 10 years,
      SBP in group 3 was lower while both uric acid and ALT in all groups were
      decreased. CONCLUSION: In patients who survived for more than 10 years after
      kidney transplantation, serum lipid levels were markedly elevated, indicating the
      increase of cardiovascular risk factors for patients, which might impact long
      term survival benefit.

PMID- 25073405
TI  - Blame it on the alcohol: the influence of alcohol consumption during adolescence,
      the transition to adulthood, and young adulthood on one-time sexual hookups.
AB  - Using public-use data from the National Longitudinal Study of Adolescent Health
      (n = 3,733) and the life-span developmental perspective, the current study sought
      to determine whether global reports of alcohol use, binge drinking, and
      drunkenness are best represented as indicators of a latent alcohol consumption
      construct during adolescence, the transition to adulthood, and young adulthood.
      We also examined the predictive power of alcohol consumption during each
      developmental period on the total number of one-time sexual hookups reported in
      young adulthood. A confirmatory factor analysis revealed alcohol use, binge
      drinking, and drunkenness are consistent indicators of a latent alcohol
      consumption variable over time, although the mean levels of the indicators were
      significantly lower during adolescence. Structural equation modeling analyses
      found alcohol consumption during the transition to adulthood and young adulthood
      predicted one-time sexual hookups in young adulthood, but alcohol consumption
      during the transition to adulthood exhibited the strongest association with
      hooking up. Implications for research, theory, and practice are discussed.

PMID- 25073406
TI  - Pleiotrophin differentially regulates the rewarding and sedative effects of
      ethanol.
AB  - Pleiotrophin (PTN) is a cytokine with important roles in dopaminergic neurons. We
      found that an acute ethanol (2.0 g/kg, i.p.) administration causes a significant
      up-regulation of PTN mRNA and protein levels in the mouse prefrontal cortex,
      suggesting that endogenous PTN could modulate behavioural responses to ethanol.
      To test this hypothesis, we studied the behavioural effects of ethanol in PTN
      knockout (PTN(-/-) ) mice and in mice with cortex- and hippocampus-specific
      transgenic PTN over-expression (PTN-Tg). Ethanol (1.0 and 2.0 g/kg) induced an
      enhanced conditioned place preference in PTN(-/-) compared to wild type mice,
      suggesting that PTN prevents ethanol rewarding effects. Accordingly, the
      conditioning effects of ethanol were completely abolished in PTN-Tg mice. The
      ataxic effects induced by ethanol (2.0 g/kg) were not affected by the genotype.
      However, the sedative effects of ethanol (3.6 g/kg) tested in a loss of righting
      reflex paradigm were significantly reduced in PTN-Tg mice, suggesting that up
      regulation of PTN levels prevents the sedative effects of ethanol. These results
      indicate that PTN may be a novel genetic factor of importance in alcohol use
      disorders, and that potentiation of the PTN signalling pathway may be a promising
      therapeutic strategy in the treatment of these disorders.

PMID- 25073407
TI  - Analysis of prices paid by low-income countries - how price sensitive is
      government demand for medicines?
AB  - BACKGROUND: Access to medicines is an important health policy issue. This paper
      considers demand structures in a selection of low-income countries from the
      perspective of public authorities as the evidence base is limited. Analysis of
      the demand for medicines in low-income countries is critical for effective
      pharmaceutical policy where regulation is less developed, health systems are cash
      constrained and medicines are not typically subsidised by a public health
      insurance system METHODS: This study analyses the demand for medicines in low
      income countries from the perspective of the prices paid by public authorities.
      The analysis draws on a unique dataset from World Health Organization (WHO) and
      Health Action International (HAI) using 2003 data on procurement prices of
      medicines across 16 low-income countries covering 48 branded drugs and 18
      therapeutic categories. Variation in prices, the mark-ups over marginal costs and
      estimation of price elasticities allows assessment of whether these elasticities
      are correlated with a country's national income. RESULTS: Using the Ramsey
      pricing rule, the study's findings suggest that substantial cross-country
      variation in prices and mark-ups exist, with price elasticities ranging from -1
      to -2, which are weakly correlated with national income. CONCLUSIONS: Government
      demand for medicines thus appears to be price elastic, raising important policy
      implications aimed at improving access to medicines for patients in low-income
      countries.

PMID- 25073408
TI  - The transcriptional activator Pog1 controls cell cycle, and its phosphorylated
      form is downregulated by the ubiquitin ligase Dma2 in Saccharomyces cerevisiae.
AB  - The POG1 gene in Saccharomyces cerevisiae is suggested to encode the
      transcriptional activator that promotes growth in the presence of a mating
      pheromone. We previously showed that the overexpression of POG1 conferred
      tolerance to high concentrations of LiCl and sugar on laboratory and baker's
      yeast strains, respectively. Here, the overexpression of POG1 was shown to induce
      cell cycle delay at the G1 phase and morphological abnormality. In addition, by
      yeast two-hybrid screening, the really interesting new gene (RING)-type ubiquitin
      ligase Dma2, which is involved in cell cycle regulation, was identified as the
      protein interacting with Pog1. The gene mutation and deletion analysis revealed
      that the interaction between Pog1 and Dma2 requires the phosphorylation of Thr253
      in Pog1 and the forkhead-associated domain in Dma2. The phosphorylation status of
      Pog1 changed along with progression of the cell cycle. Interestingly, our results
      showed that Pog1 might be ubiquitinated by Dma2, but a dephosphorylation-mimic
      mutation in POG1 increased the cellular Pog1 level possibly due to the failure of
      ubiquitination. Furthermore, growth of the dma1/2-disrupted strain was greatly
      inhibited by the overexpression of POG1. These results suggest that Pog1 controls
      the cell cycle and its phosphorylated form is downregulated by Dma2. 

PMID- 25073410
TI  - Facial steatocystoma multiplex combined with eruptive vellus hair cysts: a
      hybrid?

PMID- 25073409
TI  - Water sources as reservoirs of Vibrio cholerae O1 and non-O1 strains in Bepanda,
      Douala (Cameroon): relationship between isolation and physico-chemical factors.
AB  - BACKGROUND: Cholera has been endemic in Douala since 1971. Most outbreaks start
      from Bepanda, an overcrowded neighbourhood with poor hygiene and sanitary
      conditions. We investigated water sources in Bepanda as reservoirs of Vibrio
      cholerae, the causative agent of cholera, determined its antibiotic
      susceptibility and some physico-chemical characteristics that could maintain the
      endemicity of this organism in Bepanda. METHODS: Three hundred and eighteen water
      samples collected from 45 wells, 8 taps and 1 stream from February to July 2009
      were analyzed for V. cholerae using standard methods. Isolates were characterized
      morphologically, biochemically and serologically. The disc diffusion technique
      was employed to investigate antibiotic susceptibility. Differences in prevalence
      of organism between seasons were analysed. Correlation strength and direction of
      association between physico-chemical parameters and occurrence of V. cholerae was
      analyzed using the Kendall tau_b non-parametric correlation. This was further
      confirmed with the forward-stepwise binary logistic regression. RESULTS: Eighty
      seven (27.4%) samples were positive for V. cholerae. Isolation was highest from
      wells. The organism was isolated in the rainy season and dry season but the
      frequency of isolation was significantly higher (chi2 = 7.009, df = 1, P = 0.008)
      in the rainy season. Of the 96 confirmed V. cholerae isolates, 32 (33.3%)
      belonged to serogroup O1 and 64 (66.6%) were serogroup non-O1/non-O139. Isolates
      from tap (municipal water) were non-O1/non-O139 strains. Salinity had a
      significant positive correlation with isolation in the dry season (+0.267, P =
      0.015) and rainy season (+0.223, P = 0.028). The forward-stepwise method of
      binary logistic regression indicated that as pH (Wald = 11.753, df = 1), P =
      0.001) increased, odds of isolation of V. cholerae also increased (B = 1.297, S.E
      = 0.378, Exp(B) = 3.657). All isolates were sensitive to ciprofloxacin and
      ofloxacin. Multi-drug resistance was predominant among the non-O1/non-O139
      isolates. CONCLUSION: V. cholerae was found in wells and stream in both seasons.
      Cholera will continue to be a health threat in Bepanda if intervention measures
      to prevent outbreak are not implemented. Continuous monitoring of water sources
      in this and other cholera high-risk areas in Cameroon is necessary, for a better
      preparedness and control of cholera.

PMID- 25073411
TI  - FISHing for pancreatobiliary tract malignancy in endoscopic brushings enhances
      the sensitivity of routine cytology.
AB  - Pancreatobiliary tract carcinoma is a lethal disease with low survival rates and
      limited treatment options. Diagnosis is complicated by benign conditions that can
      mimic malignancy on radiological studies (e.g. primary sclerosing cholangitis or
      PSC) and the suboptimal sensitivity of endoscopic biopsy/brushings obtained by
      endoscopic retrograde cholangiopancreatography (ERCP). The detection of multiple
      chromosomal gains by fluorescence in situ hybridization (FISH), referred to as
      polysomy, has demonstrated improved sensitivity over routine cytological
      evaluation. The evaluation of brushings by both routine cytology and FISH in our
      cytopathology laboratory has been in clinical practice since 2003. Strong
      morphological and screening skills enable cytotechnologists to become proficient
      in the assessment of FISH slides, which translates into cost and time savings.
      Multiple reports from various institutions have demonstrated the utility of FISH
      for patients with and without PSC. The incorporation of routine cytology and FISH
      results into the management algorithm for patients under suspicion for
      pancreatobiliary malignancy is a testament to the clinical success of these
      cytological assays. 

PMID- 25073412
TI  - A novel scaffold geometry for chondral applications: theoretical model and in
      vivo validation.
AB  - A theoretical model of the 3D scaffold internal architecture has been implemented
      with the aim to predict the effects of some geometrical parameters on total
      porosity, Young modulus, buckling resistance and permeability of the graft. This
      model has been adopted to produce porous poly-caprolacton based grafts for
      chondral tissue engineering applications, best tuning mechanical and functional
      features of the scaffolds. Material prototypes were produced with an internal
      geometry with parallel oriented cylindrical pores of 200 MUm of radius (r) and an
      interpore distance/pores radius (d/r) ratio of 1. The scaffolds have been then
      extensively characterized; progenitor cells were then used to test their
      capability to support cartilaginous matrix deposition in an ectopic model.
      Scaffold prototypes fulfill both the chemical-physical requirements, in terms of
      Young's modulus and permeability, and the functional needs, such as surface area
      per volume and total porosity, for an enhanced cellular colonization and matrix
      deposition. Moreover, the grafts showed interesting chondrogenic potential in
      vivo, besides offering adequate mechanical performances in vitro, thus becoming a
      promising candidate for chondral tissues repair. Finally, a very good agreement
      was found between the prediction of the theoretical model and the experimental
      data. Many assumption of this theoretical model, hereby applied to cartilage, may
      be transposed to other tissue engineering applications, such as bone substitutes.

PMID- 25073413
TI  - Pathogenesis of acute and chronic diseases caused by cyprinid herpesvirus-3.
AB  - The pathogenesis of cyprinid herpesvirus-3 (CyHV-3) was studied using different
      lineages of carp/koi. After exposure to the virus, infected cells were first
      found in the skin by histopathology and by in situ hybridization. The epidermis
      of the skin was most severely damaged and often sloughed off in the fish sampled
      on days 5 through 8, and the fish that were highly sensitive to the virus died
      within 8 or 10 days after infection. Serum osmolality of the infected fish,
      particularly just before death, was significantly lower, suggesting that the
      osmotic shock consequent on the damage to the skin was the direct cause of the
      acute deaths. On the other hand, clinical and histopathological observations
      indicate that the carp of a less sensitive lineage most probably died of viral
      encephalitis around 3 weeks after infection. For these fish, the largest number
      of infected cells was found in the central nervous system (CNS) sampled on day
      12. A substantial amount of viral genome was found in the CNS of carp surviving
      more than 1 year after the infection. Thus, the CNS is probably a major target
      for CyHV-3, and the virus can persistently infect the CNS, presumably
      establishing latency.

PMID- 25073414
TI  - Abnormal fingernail beds following carbon monoxide poisoning: a case report and
      review of the literature.
AB  - INTRODUCTION: Carbon monoxide poisoning is a very common cause of death in
      accidental, suicidal, or homicidal cases throughout the world. Fingernail bed
      manifestation is reported in survivors of carbon monoxide poisoning. CASE
      PRESENTATION: A 40-year-old Caucasian woman was exposed to carbon monoxide when
      she was sleeping alone in her one-bedroom apartment; fortunately, the beeps from
      her First Alert combination smoke and carbon monoxide detector woke her and she
      was saved from any extensive health issues. The most indicative symptoms
      experienced were a severe headache, blurred vision, agitation, and confusion.
      Following contact with the Emergency Responses Services, she was promptly
      transferred to the hospital via ambulance and was treated with high-flow oxygen
      on the way. She was discharged from the emergency department on the same day, but
      carbon monoxide exposure had already had adverse effects on her fingernail beds.
      The fingernail tips were altered and appeared as if a bite had been taken out of
      their distal borders. The changes in the tips of her fingernails were
      significant, but they completely disappeared eight weeks later without any
      additional treatment. CONCLUSIONS: Worldwide, carbon monoxide poisoning is a
      potentially lethal condition that is preventable with educational programs and
      installation of carbon monoxide detectors in the home setting. Exposure to carbon
      monoxide frequently goes unrecognized until it is too late and causes silent
      death. To the best of the authors' knowledge, this is the first report in the
      literature of fingernail bed manifestations in a survivor of carbon monoxide
      poisoning.

PMID- 25073415
TI  - Lethal Encephalitozoon cuniculi genotype III infection in Steppe lemmings
      (Lagurus lagurus).
AB  - Microsporidia are ubiquitous, spore-forming, intracellular parasites infecting
      invertebrates and vertebrates. Some of them are important opportunistic pathogens
      in humans, including three species of genus Encephalitozoon. Intraspecies genetic
      variation with a different range of hosts is known in Encephalitozoon cuniculi
      distinguishing four genotypes. Recently, E. cuniculi is often observed in pet
      animals, mainly E. cuniculi genotype I in pet rabbits. This study described a
      fatal encephalitozoonosis in a group of pet rodents Steppe lemmings (Lagurus
      lagurus). The animals were presented with progressive weight loss, aggression,
      cannibalism, purulent conjunctivitis and hind limb paresis. Death occurred within
      48 h after the onset of clinical signs. The group comprised of 15 animals was
      affected and died within a period of three months. Post-mortal examination did
      not show any macroscopic changes. Microsporidial vacuoles with typical spores
      were found in brain and kidney tissues and E. cuniculi DNA in all tested organs.
      The internal transcribed spacer region (ITS) of rRNA gene showed 100% homology
      with E. cuniculi genotype III previously identified in dogs, tamarin colonies
      from zoos, swine, birds and humans. Pet lemmings could represent a new potential
      source of the infection for their breeders.

PMID- 25073416
TI  - Colonization by endophytic Ochrobactrum anthropi Mn1 promotes growth of Jerusalem
      artichoke.
AB  - The Ochrobactrum anthropi Mn1 strain, taxonomically identified using 16S
      ribosomal DNA sequence, was isolated from roots of Jerusalem artichoke. Its
      endophytic colonization was investigated microscopically using green fluorescent
      protein introduced by vector pHC60. The strain entered Jerusalem artichoke
      tissues through the root, and was localized in the roots and stems. The plant
      growth-promoting (PGP) effects of O. anthropi Mn1 were assessed in greenhouse as
      well as field trials with different nitrogen supplies. Only under moderate to
      ample nitrogen supply, could O. anthropi Mn1 promoted growth of host plant. The
      PGP effects of the strain were symbiotic nitrogen fixation, root morphological
      optimization and enhanced nutrient uptake. We hypothesize that the symbiotic
      interspecies interaction might be quorum sensing related. 

PMID- 25073418
TI  - Gender-specific effects of a phytogenic feed additive on performance, intestinal
      physiology and morphology in broiler chickens.
AB  - To date, most studies published were carried out on broilers of the same sex, and
      possible gender-specific effects of phytogenic substances have not been
      investigated so far. A 3 * 2 factorial study was performed to examine gender
      specific effects of a PFA at two dietary levels (150, 1500 ppm) on growth
      performance, carcass traits and gastrointestinal attributes in broiler chickens
      versus an untreated control group. The addition of 150 ppm of the PFA led to a
      downregulation of trypsinogen mRNA in pancreas compared with the control group (p
      < 0.05). The number of goblet cells decreased in jejunum compared with the
      unsupplemented group, whereby this effect was more pronounced in male birds (p <
      0.05). Furthermore, higher methylamine contents compared with the control group
      were measured (p < 0.01). In proximal ileum, female birds, supplemented with 150
      ppm PFA, had lower crypt depths than their litters in the 1500 ppm treatment (p <
      0.05). In distal ileum, villus height:crypt depth ratio was higher in birds fed
      the PFA at 150 ppm than in the control group (p < 0.05). The 1500 ppm dosage of
      the PFA increased jejunal histamine concentration compared with the negative
      control group (p < 0.05). Jejunal histamine concentration was also affected by
      the interaction PFA * sex (p < 0.05). Regardless of inclusion level, total amount
      of biogenic amines and other microbial metabolites in digesta samples was not
      affected by the PFA. These results demonstrate variable, partially gender
      specific effects of the tested PFA. Although the supplementation of 150 ppm
      showed little effect on mRNA expression level of selected marker genes for
      nutrient digestion, beneficial effects on gut morphology were observed. The 10
      fold higher dosage of the PFA did not adversely affect growth performance as well
      as most investigated parameters compared with the control group. 

PMID- 25073419
TI  - The role of encapsulation by beta-cyclodextrin in the interaction of raloxifene
      with macromolecular targets: a study by spectroscopy and molecular modeling.
AB  - We report the binding of the drug raloxifene with Calf thymus DNA (ctDNA) and
      bovine serum albumin (BSA) in the presence and absence of beta-cyclodextrin (beta
      CD) and explain the influence of beta-cyclodextrin on the binding of the drug to
      macromolecules. UV-Vis absorption, fluorescence, proton nuclear magnetic
      resonance and two-dimensional rotating-frame nuclear overhauser effect
      spectroscopic techniques are used to study the stoichiometry and the binding
      strength of the complexes. Molecular modeling is used in combination with other
      techniques to propose the structure of the inclusion complex and the interaction
      with ctDNA. The Stern-Volmer quenching constants of the interaction of raloxifene
      with ctDNA in aqueous and in beta-CD solution are compared. The competition for
      binding of ctDNA with raloxifene and Methylene Blue is studied. The apparent
      binding constant and the number of binding sites for the binding of raloxifene
      with BSA in aqueous solution are significantly different from those in the
      presence of beta-CD. The influence of beta-CD on the binding of the small
      molecules with biological macromolecules is discussed. We infer that the binding
      strengths between raloxifene and macromolecules, viz., ctDNA and BSA are
      influenced by the beta-CD encapsulation. These results may suggest new ways to
      tune the drug binding to biomacromolecules by encapsulating specific moieties of
      drugs. 

PMID- 25073420
TI  - Multiple driver distractions: a systemic transport problem.
AB  - Strategies to contend with driver distraction may no longer be sufficient for the
      emerging variety of contemporary driver distractions. A more systematic and
      systemic approach holds promise for improved road safety but is not currently
      being developed. This systematic review of multiple driver distractions aims to
      address this gap and presents two key findings. Systematic classification of
      distracting tasks with respect to driving is challenging, and engagement with
      Multiple-Additional-to-Driving (MAD) tasks is almost universally detrimental to
      driving performance. A model is presented to assist in systematically
      characterising multiple driver demands. Identified literature is placed into
      context using the model and shortfalls are identified. 

PMID- 25073421
TI  - Vascular patterns in mature hypertrophic burn scars treated with fractional CO2
      laser.
AB  - BACKGROUND AND OBJECTIVE: Fractional CO2 laser has recently emerged as a
      promising therapeutic modality to improve the texture and appearance of burn
      scars. An issue in many burn scars is persistent erythema, which traditionally
      has been treated with vascular lasers. Interestingly, fractional CO2 lasers have
      been shown to improve the appearance of burn scars, including erythema, but no
      mechanism has been proposed for this change. Our objective is to evaluate the
      histopathologic changes in vasculature in burn scars treated with fractionated
      CO2 laser, and to attempt to describe the mechanism behind reduced erythema
      following treatment. STUDY DESIGN/MATERIALS AND METHODS: Uncontrolled,
      prospective study of ten patients with mature burn scars, from a clinical and
      histological perspective. Biopsy specimens were obtained before and 2 months
      after 3 treatment sessions. Anti-CD31 immunostaining was performed to highlight
      vascular patterns in biopsy specimens. RESULTS: In histological analysis, an
      increase in vascular density, particularly of small caliber vessels, was seen
      following treatment, with an 82.6% average increase in vasculature (P = 0.028).
      This increase in vascularity correlated with a decrease in clinical erythema and
      vascularity scores, measured using the Vancouver Scar Scale. CONCLUSION: Mature
      hypertrophic burn scars treated with a fractional CO2 laser showed a
      statistically significant increase in vascular density in the superficial dermis.
      A non-statistical decrease in clinically perceived erythema and improvement of
      overall appearance was seen. To our knowledge, this is the first report of
      increased vascular density in burn scars treated with fractional CO2 laser and
      suggests our prior assumptions on causes of erythema in mature hypertrophic scars
      may need to be challenged.

PMID- 25073423
TI  - MDG 6 and beyond: from halting and reversing AIDS to ending the epidemic.

PMID- 25073424
TI  - Estimating the amount of FDG uptake in physiological tissues.
AB  - INTRODUCTION: It is known that for a fixed amount of injected tracer, the amount
      available for a tissue of interest will be less if other tissues show intense
      uptake. The aim of this study was to estimate the magnitude of 2-deoxy-2
      [(18)F]fluoro-D-glucose (18FDG) uptake amount in physiological tissues that may
      show an intense uptake in current clinical practice. METHODS: A formula was
      established providing an estimate of the percentage of injected 18FDG molecules
      (P; in %) that are irreversibly trapped in an 18FDG-positive tissue during a PET
      examination. RESULTS: P ? 0.17*exp(-lambdat(acq))*TLG/W, where lambda is the
      (18)F physical decay constant, t(acq) is the injection-acquisition time delay,
      TLG is total lesion glycolysis (g) and W is the patient weight (kg). The
      magnitude of P was calculated in two patients showing an intense uptake in brown
      fat, myocardium and bowels: 0.5, 3.5, and 4.2% respectively. CONCLUSIONS: A
      formula is available to quickly estimate the amount of 18FDG uptake in tissues.
      We suggest that the accumulation of different physiological uptakes may actually
      affect SUV quantification in a tissue of interest.

PMID- 25073422
TI  - Mitochondria-mediated apoptosis in mammals.
AB  - The mitochondria-mediated caspase activation pathway is a major apoptotic pathway
      characterized by mitochondrial outer membrane permeabilization (MOMP) and
      subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP
      is regulated by the Bcl-2 family of proteins. This pathway plays important roles
      not only in normal development, maintenance of tissue homeostasis and the
      regulation of immune system, but also in human diseases such as immune disorders,
      neurodegeneration and cancer. In the past decades the molecular basis of this
      pathway and the regulatory mechanism have been comprehensively studied, yet a
      great deal of new evidence indicates that cytochrome c release from mitochondria
      does not always lead to irreversible cell death, and that caspase activation can
      also have non-death functions. Thus, many unsolved questions and new challenges
      are still remaining. Furthermore, the dysfunction of this pathway involved in
      cancer development is obvious, and targeting the pathway as a therapeutic
      strategy has been extensively explored, but the efficacy of the targeted
      therapies is still under development. In this review we will discuss the
      mitochondria-mediated apoptosis pathway and its physiological roles and
      therapeutic implications. 

PMID- 25073427
TI  - Cardiovascular risk factors as causes for hearing impairment.
AB  - The purpose of this paper is to provide a contemporary review of the correlation
      between cardiovascular risk factors (CVRFs) and hearing impairment (HI) . We
      conducted a comprehensive review of the literature in order to assess the effects
      of the different CVRFs on HI. We focused on the pathological findings in the
      inner ear and their correlation with cochlear function in population-based
      studies. We found that CVRFs adversely affect hearing acuity. HI diagnosis should
      be accompanied by detecting and treating CVRFs, according to the presented
      outline, which may augment hearing rehabilitation and improve the general health
      and the well-being of the patient. (c) 2014 S. Karger AG, Basel. 

PMID- 25073425
TI  - Molecular targets of the multifunctional iron-chelating drug, M30, in the brains
      of mouse models of type 2 diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Neurodegenerative diseases are now recognized to be
      multifunctional, whereby a heterogeneous set of reactions acts independently or
      cooperatively, leading eventually to the demise of neurons. This has led our
      group to design and synthesize the multifunctional, nontoxic, brain-permeable,
      iron chelator compound M30 with a range of pharmacological properties. Here, we
      have characterized the molecular targets of M30 in the brains of animal models of
      type 2 diabetes mellitus (T2DM). EXPERIMENTAL APPROACH: Effects of M30 on
      molecular mechanisms associated with neuroprotection in the CNS were investigated
      in the high-fat diet (HFD) and ob/ob transgenic mouse models of T2DM, using real
      time PCR and Western blotting analyses. Brain monoamine oxidase (MAO) activity
      and catecholamine levels, and peripheral glucose tolerance were assayed after
      treatment in vivo. KEY RESULTS: M30 increased cerebral levels of insulin and
      insulin receptor and phosphorylated-GSK-3beta in HFD mice, compared with vehicle
      treated HFD mice. In both T2DM mice models, M30 treatment significantly up
      regulated cerebral hypoxia-inducible factor (HIF)-1alpha protein levels and
      induced the expression of several HIF-1 target genes involved in neuroprotection,
      glycolysis, neurogenesis, oxidative stress and anti-inflammation. Additionally,
      M30 inhibited MAO-A and -B activities in the cerebellum. Accordingly, M30
      administration significantly reduced brain levels of dopamine metabolites and
      increased levels of 5-HT and noradrenaline. Glucose tolerance was also improved
      after M30 treatment in both models of T2DM. CONCLUSIONS AND IMPLICATIONS: In the
      brain of HFD and ob/ob transgenic mice, M30 exerted a variety of beneficial
      neuroprotective regulatory effects that may act synergistically to delay or
      prevent neurodegenerative processes associated with T2DM.

PMID- 25073426
TI  - Relationships between academic performance of medical students and their
      workplace performance as junior doctors.
AB  - BACKGROUND: Little recent published evidence explores the relationship between
      academic performance in medical school and performance as a junior doctor.
      Although many forms of assessment are used to demonstrate a medical student's
      knowledge or competence, these measures may not reliably predict performance in
      clinical practice following graduation. METHODS: This descriptive cohort study
      explores the relationship between academic performance of medical students and
      workplace performance as junior doctors, including the influence of age, gender,
      ethnicity, clinical attachment, assessment type and summary score measures (grade
      point average) on performance in the workplace as measured by the Junior Doctor
      Assessment Tool. RESULTS: There were two hundred participants. There were
      significant correlations between performance as a Junior Doctor (combined overall
      score) and the grade point average (r = 0.229, P = 0.002), the score from the
      Year 6 Emergency Medicine attachment (r = 0.361, P < 0.001) and the Written
      Examination in Year 6 (r = 0.178, P = 0.014). There was no significant effect of
      any individual method of assessment in medical school, gender or ethnicity on the
      overall combined score of performance of the junior doctor. CONCLUSION:
      Performance on integrated assessments from medical school is correlated to
      performance as a practicing physician as measured by the Junior Doctor Assessment
      Tool. These findings support the value of combining undergraduate assessment
      scores to assess competence and predict future performance.

PMID- 25073428
TI  - High diversity of MIC genes in non-human primates.
AB  - The human MHC class I (MHC-I) chain-related genes A and B (MICA and MICB) encode
      stress-induced glycoproteins, ligands for the activating receptor NKG2D. They
      display an unusually high degree of polymorphism, next only to that of classical
      MHC-I. The functional relevance and selective pressure behind this peculiar
      polymorphism, which is quite distinct from that of classical MHC-I, remain
      largely unknown. This study increases the repertoire of allelic sequences
      determined for the MIC genes of non-human primates. Sequencing (mainly exons 2,
      3, 4, 5) MIC genes of 72 Macaca fascicularis (Mafa), 63 Pan troglodytes (Patr),
      and 18 Gorilla gorilla (Gogo) individuals led to the identification of 35, 14,
      and 3 new alleles, respectively. Additionally, we confirm the existence of three
      independent MIC genes in M. fascicularis, i.e., Mafa-MICA, Mafa-MICB, and Mafa
      MICB/A, the latter being a hybrid of Mafa-MICB and Mafa-MICA. By multiple
      sequence alignment and phylogenetic analysis, we further demonstrate that the
      present day MIC genes most likely derive from a single human MICB-like ancestral
      gene. 

PMID- 25073430
TI  - Crop load and harvest maturity effects on consumer preferences for apricots.
AB  - BACKGROUND: Improving apricot fruit quality delivered to consumers is key to
      ensuring a successful apricot industry. Previous studies have focused on effects
      of either soluble solids content (SSC) or fruit firmness on consumer preferences,
      and results have been equivocal. This study evaluated the effects of crop load
      and harvest maturity how they affected on fruit SSC and firmness, and on
      subsequent consumer preferences. RESULTS: SSC of apricots was an important factor
      only when fruit were firmer than 15 N and not immature. When fruit were softer
      than 15 N, SSC had little influence on consumer liking. In general, consumers
      preferred fruit that were grown on trees thinned to approximately 10-20% less
      than typical commercial crop loads and were harvested in a more mature condition.
      Consumers also preferred fruit that had a higher sugar/acid ratio or BrimA value,
      which is the  degrees Brix - k * titratable acidity, where k is a constant that
      varies between species and cultivars depending on the specific acids and sugars
      present. High apricot flavour and juiciness were associated with greater
      sweetness. CONCLUSION: Management practices that increase fruit SSC and
      sugar/acid ratio, such as reducing crop load, will improve consumer satisfaction
      as long as fruit are harvested at an adequate maturity stage and are maintained
      in storage so that they do not soften too quickly.

PMID- 25073429
TI  - Characterization of Toll-like receptor gene expression and the pathogen agonist
      response in the antarctic bullhead notothen Notothenia coriiceps.
AB  - Notothenia coriiceps, a typical Antarctic notothenioid teleost, has evolved to
      adapt to the extreme Antarctic marine environment. We previously reported an
      extensive analysis of the Antarctic notothenioid transcriptome. In this study, we
      focused on a key component of the innate immune system, the Toll-like receptors
      (TLRs). We cloned the full-length sequence of 12 TLRs of N. coriiceps. The N.
      coriiceps transcriptome for TLR homologue (ncTLR) genes encode a typical TLR
      structure, with multiple extracellular leucine-rich regions and an intracellular
      Toll/IL-1 receptor (TIR) domain. Using phylogenetic analysis, we established that
      all of the cloned ncTLR genes could be classified into the same orthologous clade
      with other teleost TLRs. ncTLRs were widely expressed in various organs, with the
      highest expression levels observed in immune-related tissues, such as the skin,
      spleen, and kidney. A subset of the ncTLR genes was expressed at higher levels in
      fish exposed to pathogen-mimicking agonists, heat-killed Escherichia coli, and
      polyinosinic-polycytidylic acid (poly(I:C)). However, the mechanism involved in
      the upregulation of TLR expression following pathogen exposure in fish is
      currently unknown. Further research is required to elucidate these mechanisms and
      to thereby increase our understanding of vertebrate immune system evolution. 

PMID- 25073431
TI  - Electroconvulsive therapy and aerobic exercise training increased BDNF and
      ameliorated depressive symptoms in patients suffering from treatment-resistant
      major depressive disorder.
AB  - BACKGROUND: To treat patients suffering from treatment-resistant major depressive
      disorder (TR-MDD), research has focused on electroconvulsive therapy (ECT) and
      aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems
      to be key in MDD. The aims of the present study were therefore two-fold, to
      investigate in a three-arm interventional study the differential effects of ECT,
      ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive
      symptoms and 2. BDNF METHODS: 60 patients with TR-MDD (mean age: 31 years; 31.6%
      female patients) were randomly assigned either to the ECT, ECT + AET, or AET
      condition. The AET condition consisted of treadmill exercise for 30 min, three
      times a week. Both depression severity and BDNF levels were assessed at baseline
      and 4 weeks later. All patients were further treated with an SSRI standard
      medication. RESULTS: BDNF levels increased over time in all three study
      conditions. After completion of the intervention program, the ECT group showed
      significantly higher BDNF levels compared to the ECT + AET and the AET
      conditions. Depressive symptoms decreased in all three conditions over time. The
      combination of ECT + AET led to a significantly greater decrease than in either
      the ECT or AET alone conditions. BDNF levels were not associated with symptoms of
      depression. CONCLUSIONS: The pattern of results suggests that ECT, AET and
      particularly their combination are promising directions for treatment patients
      suffering from TR-MDD, and that it remains unclear to what extent BDNF is key and
      a reliable biomarker for TR-MDD.

PMID- 25073433
TI  - Confinement and controlling the effective compressive stiffness of carbyne.
AB  - Carbyne is a one-dimensional chain of carbon atoms, consisting of repeating sp
      hybridized groups, thereby representing a minimalist molecular rod or chain.
      While exhibiting exemplary mechanical properties in tension (a 1D modulus on the
      order of 313 nN and a strength on the order of 11 nN), its use as a structural
      component at the molecular scale is limited due to its relative weakness in
      compression and the immediate onset of buckling under load. To circumvent this
      effect, here, we probe the effect of confinement to enhance the mechanical
      behavior of carbyne chains in compression. Through full atomistic molecular
      dynamics, we characterize the mechanical properties of a free (unconfined chain)
      and explore the effect of confinement radius (R), free chain length (L) and
      temperature (T) on the effective compressive stiffness of carbyne chains and
      demonstrate that the stiffness can be tuned over an order of magnitude (from
      approximately 0.54 kcal mol(-1) A(2) to 46 kcal mol(-1) A(2)) by geometric
      control. Confinement may inherently stabilize the chains, potentially providing a
      platform for the synthesis of extraordinarily long chains (tens of nanometers)
      with variable compressive response. 

PMID- 25073432
TI  - TGF-beta signaling regulates fibrotic expression and activity in carpal tunnel
      syndrome.
AB  - Fibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of
      carpal tunnel syndrome (CTS). While the nature of CTS has been extensively
      studied, little is known about the etiology of this disease. We investigated SSCT
      tissue from patients with CTS and control subjects using fibrosis arrays and cell
      culture analysis. Twofold changes in fibrotic gene expression were found in
      multiple genes from patient SSCT using fibrosis arrays. This data was confirmed
      via qRT-PCR on a subset of genes; collagen I (Col1), collagen III (Col3),
      connective tissue growth factor (CTGF), transforming growth factor beta (TGF
      beta), and SMAD3 (P < 0.05) which significantly corroborate the fold changes
      found in the fibrosis arrays. To further explore the nature of SSCT fibrosis,
      cells were isolated from patient and control tissue. Col1, Col3, TGF-beta, and
      SMAD3 were highly expressed in patient SSCT fibroblasts as compared to control (P
      < 0.05). Further, fibrotic genes expression was decreased by inhibiting TGF-beta
      receptor I (TbetaRI) activity (P < 0.05). TGF-beta second messenger SMAD activity
      was significantly activated in SSCT fibroblasts from patients and this activation
      was abrogated by inhibiting TbetaRI signaling (P < 0.05). These findings suggest
      that blocking TGF-beta signaling may be an important therapeutic approach to
      treating the underlying fibrosis of SSCT in CTS patients.

PMID- 25073434
TI  - Cadmium levels in a North Carolina cohort: Identifying risk factors for elevated
      levels during pregnancy.
AB  - The objectives of this study were to examine cadmium (Cd) levels and
      relationships to demographics in an observational, prospective pregnancy cohort
      study in Durham County, North Carolina. Multivariable models were used to compare
      blood Cd levels across demographic characteristics. The relative risk of having a
      blood Cd level that exceeds the US national median (0.32 MUg/l) was estimated.
      Overall, >60% of the women had an elevated (>0.32 MUg/l) blood Cd level.
      Controlling for confounding variables, smoking was associated with 21% (95% CI:
      15-28%) increased risk for an elevated blood Cd level. High Cd levels were also
      observed in non-smokers and motivated smoking status-stratified models. Race,
      age, education, relationship status, insurance status and cotinine level were not
      associated with risk of elevated Cd levels among smokers; however, older age and
      higher cotinine levels were associated with elevated Cd levels among non-smokers.
      Taken together, more than half of pregnant women in this cohort had elevated
      blood Cd levels. Additionally, among non-smokers, 53% of the women had elevated
      levels of Cd, highlighting other potential sources of exposure. This study
      expands on the limited data describing Cd levels in pregnant populations and
      highlights the importance of understanding Cd exposures among non-smokers. Given
      the latent health risks of both smoking and Cd exposure, this study further
      highlights the need to biomonitor for exposure to toxic metals during pregnancy
      among all women of child-bearing age. 

PMID- 25073435
TI  - Estimating drinking-water ingestion and dermal contact with water in a French
      population of pregnant women: the EDDS cohort study.
AB  - The aim of the present study, a part of the Endocrine Disruptor Deux-Sevres
      (EDDS) cohort study, was to estimate water-use habits of pregnant French women.
      The study population consisted of 132 pregnant women living in Deux-Sevres
      (France) in 2012-2013, in areas where drinking water is exclusively produced by
      surface water. Drinking-water data included ingested water (tap, bottled and
      filtered) and ingestion place (home, work and elsewhere). Dermal contact with
      water included showering, bathing, swimming, spa use, hand-washing and other
      water activities. Data were collected through face-to-face interviews at second
      and third trimesters of pregnancy with a 1-day-recall questionnaire.
      Intertrimestral differences in water-use habits were assessed. Predictors of
      water ingestion and duration of dermal contact with water were assessed with
      multiple linear regressions. At the second trimester of pregnancy, the mean total
      drinking-water ingestion was 1.8+/-0.6 l per day (mean and SD), 71% of which was
      tap water. Total drinking-water ingestion was not different between both
      trimesters but ingestion place differed. Dermal contact with water estimate was
      188+/-118 and 173+/-92 min/week at second and third trimesters, respectively.
      Smoking increased water ingestion 777 ml/day 95% CI (171-1384). Duration of
      dermal contact in spring was 30 min/week 95% CI (13-48) higher than in winter.
      Obese women spend 26 min/week 95% CI (2-50) more showering than women with
      recommended weight. Our estimates of pregnant French women's exposure to water
      will help researchers to better assess water pollutant risks. 

PMID- 25073437
TI  - Mesh or no mesh: a hamletic dilemma to prevent Renal Allograft Compartment
      Syndrome (RACS).
AB  - Tension-free muscle closure is essential in kidney transplantation, both in adult
      and pediatric patients. Tight muscle closure may lead to renal allograft
      compartment syndrome either due to compression of the renal parenchyma or due to
      kinking of the renal vessels. It may also cause kinking of the transplant kidney
      ureter, wound dehiscence and incisional hernia. Many techniques have been
      proposed in an attempt to achieve tension-free closure. There is a wrong belief
      among surgeons that using prosthetic mesh may increase the incidence of infective
      complications in these immunosuppressed patients. Also, there is fear that one is
      not able to monitor the renal graft by ultrasound and perform biopsy in the
      presence of a mesh. Other alternative techniques to mesh closure include
      subcutaneous placement and intraperitonealization of the kidney transplant. These
      techniques however, are valuable when mesh closure is unfavorable or
      contraindicated as in case of a potential source of infection, like a stoma.
      Abdominal wall fasciotomy can be adjunctive to the various techniques of muscle
      closure. KEY WORDS: Abdominal mesh closure, Post transplant incisional hernia,
      Renal transplantation, Renal Allograft Compartment syndrome (RACS).

PMID- 25073436
TI  - Keeping those telomeres short! an innovative intratumoral long-term drug delivery
      system.
AB  - BACKGROUND: Telomerase activation and an alternative lengthening of telomeres
      (ALT) mechanism are two telomere-lengthening cancer cell survival mechanisms
      elicited by both chemo- and/or radiotherapy. Telomere lengthening interferes with
      cell lethality and results in the immortalization of cancer cells. To counteract
      these mechanisms, we developed a drug delivery system (DDS) consisting of a
      polymeric implant that is inserted directly into tumors. The DDS releases,
      continuously and gradually, a cationic porphyrin (PdTMPyP4) for >30 days after a
      single application, and inhibits telomerase activation. METHODS: The PdTMPyP4
      porphyrin is incorporated into a poly(co-glycolic lactic)acid (PLGA) polymer,
      solidified and cut into small rods. PdTMPyP4 release from the rods was measured
      spectrophotometrically over time. Uptake of Pd in the DNA of in L428 Hodgkins
      lymphoma cells was measured by ICP-MS, and telomerase activation by the TRAP
      assay. The rods were placed into the growth medium of cells whose growth rate was
      measured for 11 and 19 days. The cylinders were also inserted directly into KHJJ
      murine mammary tumors borne on the thighs of BALB/c mice and the tumor growth
      rate measured. RESULTS: In vitro, >10(9)Pd atoms were measured in the DNA of each
      L428 cell and telomerase activity was reduced by ~15% within 24 h. A one-time
      application of the rod in the cell medium induced a factor of >5 greater
      lethality compared to a blank rod or untreated controls. In vivo, a one-time
      insertion of the rod into tumors resulted in the retardation of the growth rate
      by factors of 3-5 compared to untreated controls. Systemic uptake after
      intratumoral insertion of the rod was negligible. CONCLUSION: The results suggest
      that the direct intratumoral insertion of a PdTMPyP4-containing polymeric rod
      would be of benefit as an adjuvant treatment for patients undergoing chemo- or
      radiotherapy. By preventing the lengthening of telomeres and therefore the
      unrestricted growth of cancer cells, our DDS will provide a significant
      therapeutic advantage to these treatments without affecting normal tissues.

PMID- 25073439
TI  - IFRD1 polymorphisms and gastric cancer risk in a Chinese population.
AB  - The association between gene polymorphisms of IFRD1 and gastric cancer is not
      clear. The aim of this study was to investigate the association between IFRD1
      polymorphisms and gastric cancer in Chinese population. Fifty-three consecutive
      patients with the diagnosis of gastric cancer were defined as the case group, and
      another 50 healthy donors were denoted as the control group. About 4 ml of
      peripheral blood was collected from each donor for extracting DNA. Finally, IFRD1
      rs7818, rs3807213, and rs6968084 SNPs were detected with polymerase chain
      reaction. C/C genotype distribution frequencies of rs6968084 and rs7817 in
      gastric cancer patients were similar with the controls (OR 0.192, 95 % CI 0.513
      2.769, P = 0.683 and OR 2.075, 95 % CI 0.744-5.792, P = 0.16, respectively).
      Patients with gastric cancer had a significantly higher frequency of rs3807213 C
      allele and rs3807213 C/C genotype than controls. (OR 4.028, 95 % CI 1.513-10.72,
      P = 0.004) (OR 3.759, 95 % CI 1.521-9.294, P = 0.003). This study suggests that
      the SNPs of IFRD1 rs7818 and rs6968084 have nothing to do with the gastric cancer
      susceptibility. The allele gene C and genotype C/C of rs3807213 SNP are involved
      in susceptibility to gastric cancer, but there were no relations when subgroup
      stratified all the three SNPs according to pathological stages.

PMID- 25073438
TI  - Molecular spectrum of KRAS, BRAF, and PIK3CA gene mutation: determination of
      frequency, distribution pattern in Indian colorectal carcinoma.
AB  - Molecular evaluation of KRAS, BRAF, and PIK3CA mutation has become an important
      part in colorectal carcinoma evaluation, and their alterations may determine the
      therapeutic response to anti-EGFR therapy. The current study demonstrates the
      evaluation of KRAS, BRAF, and PIK3CA mutation using direct sequencing in 204
      samples. The frequency of KRAS, BRAF, and PIK3CA mutations was 23.5, 9.8, and 5.9
      %, respectively. Five different substitution mutations at KRAS codon 12 (G12S,
      G12D, G12A, G12V, and G12C) and one substitution type at codon 13 (G13D) were
      observed. KRAS mutations were significantly higher in patients who were >50
      years, and were associated with moderate/poorly differentiated tumors and
      adenocarcinomas. All mutations in BRAF gene were of V600E type, which were
      frequent in patients who were <= 50 years. Unlike KRAS mutations, BRAF mutations
      were more frequent in well-differentiated tumors and right-sided tumors. PIK3CA
      E545K was the most recurrent mutation while other mutations detected were T544I,
      Q546R, H1047R, G1049S, and D1056N. No significant association of PIK3CA mutation
      with age, tumor differentiation, location, and other parameters was noted. No
      concomitant mutation of KRAS and BRAF mutations was observed, while,
      interestingly, five cases showed concurrent mutation of KRAS and PIK3CA
      mutations. In conclusion, to our knowledge, this is the first study to evaluate
      the PIK3CA mutation in Indian CRC patients. The frequency of KRAS, BRAF, and
      PIK3CA was similar to worldwide reports. Furthermore, identification of molecular
      markers has unique strengths, and can provide insights into the pathogenic
      process and help optimize personalized prevention and therapy.

PMID- 25073440
TI  - Function and regulation of the channel-kinase TRPM7 in health and disease.
AB  - Transient receptor potential (TRP) cation channels represent a large and diverse
      family of ion channels that act as important transducers of sensory information.
      The Melastatin subfamily member TRPM7 has garnered much interest due to its
      functional kinase domain; a unique feature among ion channels. TRPM7 primarily
      conducts Ca(2+) and Mg(2+) and its activity is regulated by intracellular Mg(2+),
      phospholipase C-mediated signaling and mechanical cues. A growing number of
      studies emphasize a regulatory role for TRPM7 in proliferation and cell survival
      as well as cytoskeletal reorganization during adhesion and migration. Knockout
      approaches in animal models have revealed that TRPM7 significantly contributes to
      embryonic development and organogenesis. In addition, a role for TRPM7 to the
      pathophysiology of several diseases has become evident in recent years. Here, we
      discuss how recent insights have contributed to our understanding of TRPM7
      function and regulation in health and disease. 

PMID- 25073441
TI  - Light intensity physical activity is associated with lower disability in adults
      with or at risk of knee osteoarthritis.

PMID- 25073442
TI  - Molecular characterisation of Escherichia coli from dead broiler chickens with
      signs of colibacillosis and ready-to-market chicken meat in the West Bank.
AB  - 1. The aim of this work was to compare a group of virulence-associated
      characteristics of Escherichia coli isolates from broiler chickens that had died
      with signs of colibacillosis against E. coli isolates from ready-to-market
      chicken meat in the West Bank. 2. The isolates were investigated to determine the
      virulence factor (VF) profile, phylogenetic group and the presence of extended
      spectrum beta-lactamase (ESBL). A total of 66 avian pathogenic E. coli (APEC)
      strains from different affected broiler farms and 21 E. coli isolates from ready
      to-market chicken carcasses (hereinafter called meat strains) from 8 slaughter
      houses were analysed. 3. The overall content of VFs was significantly higher (P <
      0.05) among APEC strains, with over 75% of APEC strains having >=4 VFs, while
      over 75% of the meat strains had <4 VFs. The VFs iss, astA and iucD were
      frequently detected in APEC and meat strains, whereas cvi, papC, vat, tsh and
      irp2 occurred more significantly in APEC strains. Phylogenetic typing showed that
      67% of the meat strains belonged to group B2. Phylogroup D was predominant (50%)
      in the APEC strains. Using double disc diffusion and polymerase chain reaction
      (PCR), 10.6% of the APEC and 9.5% of the meat strains were determined to be ESBL
      positive. 4. Our findings show that the VFs papC, vat, irp2 and to a lesser
      extent tsh and cvi are significantly more prevalent in APEC strains. The results
      demonstrate that chicken meat can be contaminated with APEC strains (>=4 VF). A
      significant percentage of the meat strains fall in the B2 group, which is a
      phylogroup largely associated with human pathogenic ExPEC strains. The results of
      ESBL screening indicated that broiler chicken products in Palestine represent a
      potential reservoir of ESBL genes and therefore could be considered a possible
      public health risk.

PMID- 25073443
TI  - Ultrathin cellulose nanosheet membranes for superfast separation of oil-in-water
      nanoemulsions.
AB  - Oily wastewater is generated in diverse industrial processes, and its treatment
      has become crucial due to increasing environmental concerns. Herein, novel
      ultrathin nanoporous membranes of cellulose nanosheets have been fabricated for
      separation of oil-in-water nanoemulsions. The fabrication approach is facile and
      environmentally friendly, in which cellulose nanosheets are prepared by freeze
      extraction of a very dilute cellulose solution. The as-prepared membranes have a
      cellulose nanosheet layer with a cut-off of 10-12 nm and a controllable thickness
      of 80-220 nm. They allow ultrafast water permeation and exhibit excellent size
      selective separation properties. A 112 nm-thick membrane has a water flux of 1620
      l m(-2) h(-1) bar(-1) and a ferritin rejection of 92.5%. These membranes have
      been applied to remove oil from its aqueous nanoemulsions successfully, and they
      show an ultrafast and effective separation of oil-in-water nanoemulsions. The
      newly developed ultrathin cellulose membranes have a wide application in oily
      wastewater treatment, separation and purification of nanomaterials. 

PMID- 25073444
TI  - Exosomes participate in the alteration of muscle homeostasis during lipid-induced
      insulin resistance in mice.
AB  - AIMS/HYPOTHESIS: Exosomes released from cells can transfer both functional
      proteins and RNAs between cells. In this study we tested the hypothesis that
      muscle cells might transmit specific signals during lipid-induced insulin
      resistance through the exosomal route. METHODS: Exosomes were collected from
      quadriceps muscles of C57Bl/6 mice fed for 16 weeks with either a standard chow
      diet (SD) or an SD enriched with 20% palm oil (HP) and from C2C12 cells exposed
      to 0.5 mmol/l palmitate (EXO-Post Palm), oleate (EXO-Post Oleate) or BSA (EXO
      Post BSA). RESULTS: HP-fed mice were obese and insulin resistant and had altered
      insulin-induced Akt phosphorylation in skeletal muscle (SkM). They also had
      reduced expression of Myod1 and Myog and increased levels of Ccnd1 mRNA,
      indicating that palm oil had a deep impact on SkM homeostasis in addition to
      insulin resistance. HP-fed mouse SkM secreted more exosomes than SD-fed mouse
      SkM. This was reproduced in-vitro using C2C12 cells pre-treated with palmitate,
      the most abundant saturated fatty acid of palm oil. Exosomes from HP-fed mice,
      EXO-Post Palm and EXO-Post Oleate induced myoblast proliferation and modified the
      expressions of genes involved in the cell cycle and muscle differentiation but
      did not alter insulin-induced Akt phosphorylation. Lipidomic analyses showed that
      exosomes from palmitate-treated cells were enriched in palmitate, indicating that
      exosomes likely transfer the deleterious effect of palm oil between muscle cells
      by transferring lipids. Muscle exosomes were incorporated into various tissues in
      vivo, including the pancreas and liver, suggesting that SkM could transfer
      specific signals through the exosomal route to key metabolic tissues.
      CONCLUSIONS/INTERPRETATION: Exosomes act as 'paracrine-like' signals and modify
      muscle homeostasis during high-fat diets.

PMID- 25073445
TI  - Potential viral pathogenic mechanism in human type 1 diabetes.
AB  - In type 1 diabetes, as a result of as yet unknown triggering events, auto
      aggressive CD8(+) T cells, together with a significant number of other
      inflammatory cells, including CD8(+) T lymphocytes with unknown specificity,
      infiltrate the pancreas, leading to insulitis and destruction of the insulin
      producing beta cells. Type 1 diabetes is a multifactorial disease caused by an
      interactive combination of genetic and environmental factors. Viruses are major
      environmental candidates with known potential effects on specific key points in
      the pathogenesis of type 1 diabetes and recent findings seem to confirm this
      presumption. However, we still lack well-grounded mechanistic explanations for
      how exactly viruses may influence type 1 diabetes aetiology. In this review we
      provide a summary of experimentally defined viral mechanisms potentially involved
      in the ontology of type 1 diabetes and discuss some novel hypotheses of how
      viruses may affect the initiation and natural history of the disease. 

PMID- 25073446
TI  - Primary implant stability in augmented sinuslift-sites after completed bone
      regeneration: a randomized controlled clinical study comparing four subantrally
      inserted biomaterials.
AB  - Implant-Insertion-Torque-Value (ITV) proved to be a significant clinical
      parameter to predict long term implant success-rates and to decide upon immediate
      loading. The study evaluated ITVs, when four different and commonly used
      biomaterials were used in sinuslift-procedures compared to natural subantral bone
      in two-stage-implant-procedures. The tHUCSL-INTRALIFT-method was chosen for
      sinuslifting in 155 sinuslift-sites for its minimal invasive transcrestal
      approach and scalable augmentation volume. Four different biomaterials were
      inserted randomly (easy-graft CRYSTAL n = 38, easy-graft CLASSIC n = 41, NanoBone
      n = 42, BioOss n = 34), 2 ccm in each case. After a mean healing period of 8,92
      months uniform tapered screw Q2-implants were inserted and Drill-Torque-Values
      (DTV) and ITV were recorded and compared to a group of 36 subantral sites without
      need of sinuslifting. DTV/ITV were processed for statistics by ANOVA-tests. Mean
      DTV/ITV obtained in Ncm were: Control Group 10,2/22,2, Bio-Oss 12,7/26,2,
      NanoBone 17,5/33,3, easy-graft CLASSIC 20,3/45,9, easy-graft CRYSTAL 23,8/56,6
      Ncm, significance-level of differences throughout p < 0,05. Within the limits of
      this study the results suggest self-hardening solid-block-like bone-graft
      materials to achieve significantly better DTV/ITV than loose granulate
      biomaterials for its suspected improvement of vascularization and mineralization
      of the subantral scaffold by full immobilization of the augmentation site towards
      pressure changes in the human sinus at normal breathing.

PMID- 25073447
TI  - Response of heavy-drinking voluntary and mandated college students to a peer-led
      brief motivational intervention addressing alcohol use.
AB  - Little is known about the way in which mandated and heavy-drinking voluntary
      students comparatively respond to peer-led brief motivational interventions
      (BMIs) and the mediators and moderators of intervention effects. Research
      suggests that mandated students may be more defensive due to their involvement in
      treatment against their will and this defensiveness, in turn, may relate to
      treatment outcome. Furthermore, it is not clear how mandated and heavy-drinking
      voluntary students perceived satisfaction with peer-led BMIs relates to treatment
      outcomes. Using data from two separate randomized controlled trials, heavy
      drinking college students (heavy-drinking voluntary, n = 156; mandated, n = 82)
      completed a peer-led brief motivational intervention (BMI). Both mandated and
      heavy-drinking volunteer students significantly reduced drinking behaviors at 3
      month follow-up, reported high levels of post-intervention session satisfaction,
      yet no effects for mediation or moderation were found. Findings offer continued
      support for using peer counselors to deliver BMIs; however, results regarding the
      mechanisms of change were in contrast to previous findings. Implications for
      treatment and future areas of research are discussed.

PMID- 25073448
TI  - Neural and cognitive correlates of the common and specific variance across
      externalizing problems in young adolescence.
AB  - Longitudinal and family-based research suggests that conduct disorder, substance
      misuse, and ADHD involve both unique forms of dysfunction as well as more
      specific dysfunctions unique to each condition. Using direct measures of brain
      function, this study also found evidence in both unique and disorder-specific
      perturbations. 

PMID- 25073449
TI  - Uranium and cadmium provoke different oxidative stress responses in Lemna minor
      L.
AB  - Common duckweed (Lemna minor L.) is ideally suited to test the impact of metals
      on freshwater vascular plants. Literature on cadmium (Cd) and uranium (U)
      oxidative responses in L. minor are sparse or, for U, non-existent. It was
      hypothesised that both metals impose concentration-dependent oxidative stress and
      growth retardation on L. minor. Using a standardised 7-day growth inhibition
      test, the adverse impact of these metals on L. minor growth was confirmed, with
      EC50 values for Cd and U of 24.1 +/- 2.8 and 29.5 +/- 1.9 MUm, respectively, and
      EC10 values of 1.5 +/- 0.2 and 6.5 +/- 0.9 MUm, respectively. The metal-induced
      oxidative stress response was compared through assessing the activity of
      different antioxidative enzymes [catalase, glutathione reductase, superoxide
      dismutase (SOD), ascorbate peroxidase (APOD), guaiacol peroxidase (GPOD) and
      syringaldizyne peroxidase (SPOD)]. Significant changes in almost all
      antioxidative enzymes indicated their importance in counteracting the U- and Cd
      imposed oxidative burden. However, some striking differences were also observed.
      For activity of APODs and SODs, a biphasic but opposite response at low Cd
      compared to U concentrations was found. In addition, Cd (0.5-20 MUm) strongly
      enhanced plant GPOD activity, whereas U inhibited it. Finally, in contrast to Cd,
      U up to 10 MUm increased the level of chlorophyll a and b and carotenoids. In
      conclusion, although U and Cd induce similar growth arrest in L. minor, the U
      induced oxidative stress responses, studied here for the first time, differ
      greatly from those of Cd.

PMID- 25073450
TI  - Pain, anxiety, and negative outcome expectations for activity: do negative
      psychological profiles differ between the inactive and active?
AB  - OBJECTIVE: Adherence to physical activity at >=150 minutes/week has proven to
      offer disease management and health-promoting benefits among adults with
      arthritis. While highly active people seem undaunted by arthritis pain and are
      differentiated from the moderately active by adherence-related psychological
      factors, knowledge about inactive individuals is lacking. This knowledge may
      identify what to change in order to help inactive people begin and maintain
      physical activity. The present study examined the planned, self-regulated
      activity of high, moderate, and inactive individuals to determine if differences
      existed in negative psychological factors. METHODS: Adults with a medical
      diagnosis of arthritis completed online measures of physical activity, perceived
      pain intensity, pain anxiety, and negative disease-related outcome expectations
      from being active. High active (n = 94), moderately active (n = 77), and inactive
      (n = 104) groups were identified. RESULTS: A significant multivariate analysis of
      covariance revealed group differences (P < 0.001). Followup analyses indicated
      that inactive participants had the most negative psychological profile. Inactive
      participants reported that negative disease-related outcomes expectancies were
      more distressing and likely to occur than either group of active participants and
      expressed greater pain intensity and pain anxiety than the highly active
      participants (P < 0.05 for all). CONCLUSION: Identifying differences in negative
      psychological factors aids in the understanding of differential adherence between
      activity groups and highlights possible factors to change in future intervention
      and research.

PMID- 25073451
TI  - Associations between muscle strength, spirometric pulmonary function and mobility
      in healthy older adults.
AB  - Pathological obstruction in lungs leads to severe decreases in muscle strength
      and mobility in patients suffering from chronic obstructive pulmonary disease.
      The purpose of this study was to investigate the interdependency between muscle
      strength, spirometric pulmonary functions and mobility outcomes in healthy older
      men and women, where skeletal muscle and pulmonary function decline without
      interference of overt disease. A total of 135 69- to 81-year-old participants
      were recruited into the cross-sectional study, which was performed as a part of
      European study MyoAge. Full, partial and no mediation models were constructed to
      assess the interdependency between muscle strength (handgrip strength, knee
      extension torque, lower extremity muscle power), spirometric pulmonary function
      (FVC, FEV1 and FEF50) and mobility (6-min walk and Timed Up and Go tests). The
      models were adjusted for age, sex, total fat mass, body height and site of
      enrolment. Partial mediation models, indicating both direct and pulmonary
      function mediated associations between muscle strength and mobility, fitted best
      to the data. Greater handgrip strength was significantly associated with higher
      FVC, FEV1 and FEF50 (p < 0.05). Greater muscle power was significantly associated
      with better performance in mobility tests. Results suggest that decline in
      mobility with aging may be caused by decreases in both muscle strength and power
      but also mediated through decreases in spirometric pulmonary function. Future
      longitudinal studies are warranted to better understand how loss of function and
      mass of the respiratory muscles will affect pulmonary function among older people
      and how these changes are linked to mobility decline.

PMID- 25073453
TI  - Identifying training modalities to improve multitasking in older adults.
AB  - Studies that have measured the effects of attentional training have relied on a
      range of training formats, which may vary in their efficacy. In particular, it is
      unclear whether programs that practice dual-tasking are more effective in
      improving divided attention than programs focusing on flexible allocation
      priority training. The aims of this study were as follows: (1) to compare the
      efficacy of different types of attentional training formats and (2) to assess
      transfer to distal measures. Forty-two healthy older adults were randomly
      assigned to one of three training groups. In the SINGLE training condition,
      participants practiced a visual detection and an alphanumeric equation task in
      isolation. In the FIXED training condition, participants practiced both tasks
      simultaneously with equal attention allocated to each. In the VARIABLE training
      condition, participants varied the attentional priority allocated to each task.
      After training, all participants improved their performance on the alphanumeric
      equation task when performed individually, including those in the SINGLE training
      condition. Participants in the FIXED training condition improved their divided
      attention, but only the participants in the VARIABLE training condition showed a
      greater capacity to vary their attentional priorities according to the
      instructions. Regarding transfer, all groups improved their performance on the 2
      back condition, but only the VARIABLE and FIXED conditions resulted in better
      performance on the 1-back condition. Overall, the study supports the notion that
      attentional control capacities in older adults are plastic and can be improved
      with appropriate training and that the type of training determines its impact on
      divided attention.

PMID- 25073454
TI  - Interaction of age, cognitive function, and gait performance in 50-80-year-olds.
AB  - The variability of walking gait timing increases with age and is strongly related
      to fall risk. The purpose of the study was to examine the interaction of age,
      cognitive function, and gait performance during dual-task walking. Forty-two,
      healthy men and women, 50-80 years old, completed the Mini-Mental State Exam
      (MMSE) and Trail Making Test (TMT) to assess cognitive performance and were
      separated into groups by decade of life. They then performed dual-task walking,
      at a self-selected pace, on an instrumented treadmill during three cognitive
      loading conditions: (1) no cognitive load, (2) subtraction from 100 by 1s, and
      (3) subtraction from 100 by 3s. The treadmill recorded spatiotemporal gait
      parameters that were used to calculate the mean and coefficient of variation for
      each variable over ten strides. Time to complete the TMT was positively
      correlated with age, stride time, double-limb support time, and mediolateral
      instability and was inversely correlated with single-limb support time. Subjects
      in their 70s increased their stride time and double-limb support time during the
      most challenging dual-task condition (subtraction by 3s), whereas subjects in
      their 50s and 60s did not. Across conditions, the variability of stride length,
      stride time, and single-limb support time was greatest in the 70s. Mediolateral
      instability increased only for subjects in their 70s in the subtraction by 3s
      condition. Reduced cognitive function with age makes it difficult for older
      adults to maintain a normal, rhythmical gait pattern while performing a cognitive
      task, which may place them at greater risk for falling.

PMID- 25073452
TI  - Associations between APOE and low-density lipoprotein cholesterol genotypes and
      cognitive and physical capability: the HALCyon programme.
AB  - The APOE epsilon2/3/4 genotype has been associated with low-density lipoprotein
      cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations
      with measures of cognitive performance in adults without dementia has been mixed,
      as it is for physical performance. Associations may also be evident in other
      genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the
      Life Course (HALCyon) collaborative research programme, genotypic information was
      obtained for APOE epsilon2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301
      (SORT1) from eight cohorts of adults aged between 44 and 90 + years. We
      investigated associations with four measures of cognitive (word recall, phonemic
      fluency, semantic fluency and search speed) and physical capability (grip
      strength, get up and go/walk speed, timed chair rises and ability to balance)
      using meta-analyses. Overall, little evidence for associations between any of the
      genotypes and measures of cognitive capability was observed (e.g. pooled beta for
      APOE epsilon4 effect on semantic fluency z score = -0.02; 95 % CI = -0.05 to
      0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within
      studies that negative effects of APOE epsilon4 on nonverbal ability measures
      become more apparent with age. Few genotypic associations were observed with
      physical capability measures. The findings from our large investigation of middle
      aged to older adults in the general population suggest that effects of APOE on
      cognitive capability are at most modest and are domain- and age-specific, while
      APOE has little influence on physical capability. In addition, other LDL-C
      related genotypes have little impact on these traits.

PMID- 25073455
TI  - Brief report pregnancy outcome in women assigned an ICD-9/ICD-9-CM 655.0 code
      "central nervous system malformation in fetus affecting management of pregnancy":
      can these codes aid in surveillance for central nervous system defects?
AB  - BACKGROUND: The difficulty many birth defects registries have in identifying
      early pregnancy terminations can lead to significant underreporting of certain
      types of malformations. This study was designed to determine the potential
      benefit of using maternal ICD-9 codes relating to management of pregnancy due to
      fetal anomaly in surveillance of central nervous system (CNS) defects (655.0).
      METHODS: Women assigned the ICD-9/ICD-9-CM (henceforth termed ICD-9) code 655.0
      between 1990 and 2000 were ascertained from two administrative health databases
      in Manitoba, Canada, one relating to maternal serum screening and one based on
      hospital discharges. Information was collected on the type of CNS defect
      identified and whether it was isolated or associated with other anomalies. The
      relationship of these variables to pregnancy outcome and its potential impact on
      surveillance for these types of defects was explored. RESULTS: Neural tube
      defects were the most common finding (67%) identified in the fetuses/infants of
      women assigned code 655.0, followed by hydrocephaly (20%) and Dandy-Walker
      anomaly (6%), but the proportion of neural tube defect cases declined after food
      fortification with folic acid. Termination of pregnancy occurred in ~50% of
      neural tube defect cases, 18% before 20 weeks of gestation, but was rare for
      other CNS defects. CONCLUSION: The maternal ICD-9 code 655.0 had a very high
      (97%) positive predictive value for identifying fetuses with a CNS defect; 655.00
      was particularly effective in identifying neural tube defects pregnancies
      terminated before 20 weeks gestation that would be difficult to ascertain,
      especially by passive surveillance systems using infant related data alone.

PMID- 25073456
TI  - Theoretical approach to the innovative mutation of naphthalene 1,2-dioxygenase: a
      molecular dynamics and docking study.
AB  - Polycyclic aromatic hydrocarbons are a family of ubiquitous pollutants whose
      environmental behavior has been widely studied. Different bacterial species are
      able to decompose hydrocarbons by using them as a food source. One of the best
      studied enzymes is naphthalene 1,2-dioxygenase (NDO). A practical way to optimize
      the degradation process is by mutating the protein involved, increasing both the
      degradation capacity of the enzyme and its ability to work under extreme
      environmental conditions of high temperature and low pH. Herein, we describe the
      study of NDO using molecular dynamics and docking calculations to discover new
      mutants with high degrading capabilities. We modeled eleven new mutants of NDO.
      The results indicate that increasing the size of the active site cavity in the
      mutants allowed for the insertion of high molecular weight PAHs. Additionally,
      the physicochemical properties of the NDO active sites make the sites well suited
      to interactions with PAHs, so most amino-acid modifications should not result in
      significantly altered behavior of NDO. 

PMID- 25073457
TI  - Insight into HIV-1 reverse transcriptase-aptamer interaction from molecular
      dynamics simulations.
AB  - Human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT) is considered to
      be one of the key targets for antiviral drug therapy. The emergence of the
      aptamers as potential inhibitors against HIV-1 reverse transcriptase has
      attracted the attention of the scientific community because these macromolecules
      can effectively inhibit HIV-1 RT with between micromolar to picomolar
      concentrations. However, it is not clear how aptamers interact with HIV-1 RT. We
      have undertaken a molecular dynamics (MD) study in order to gain a keen insight
      into the conformational dynamics of HIV-1 RT on the formation of a complex with
      an aptamer or DNA substrate. We have therefore employed three separate models:
      apo HIV-1 RT, HIV-1 RT with a bound RNA aptamer, and HIV-1 RT with a bound DNA
      substrate. The results show that HIV-1 RT complex with an aptamer was more stable
      than that with DNA substrate. It was found that the aptamer interacted with HIV-1
      RT in a fingers-and-thumb-closed conformation, at the bound at the nucleic acid
      substrate binding site. We identified key residues within the HIV-1 RT-aptamer
      complex in order to help design, develop, and test a new aptamer based on
      therapies in the future. 

PMID- 25073458
TI  - CETP gene polymorphism in the caucasian population of West Siberia and in groups
      contrast by total serum cholesterol levels.
AB  - TaqIB polymorphism of the gene encoding cholesterol ester transporting protein
      (CETP) was analyzed in the Caucasian population of West Siberia and in groups
      contrast by total serum cholesterol content. The patients were selected for the
      study from the main sample of HAPIEE project (9600 examined subjects aged 45-69
      years, 50% men). Analysis was carried out in 293 patients with high levels of
      total cholesterol (>300 mg/dl), 293 patients with normal and low levels of total
      cholesterol (<200 mg/dl), and 265 patients represented the population sample
      (mean level of total cholesterol 235.8+/-43.9 mg/dl). The frequencies of B1B1,
      B1B2, and B2B2 genotypes in the population were 27.5, 54.8, and 17.7%,
      respectively. The incidence of allele B2 was 45.1, 45.2, and 50.2% in the
      population and in groups with normal and high total cholesterol levels,
      respectively (p>0.05). Associations of CETP gene TaqIB (rs708272) polymorphism
      with HDL cholesterol levels was detected in groups with high and low total
      cholesterol levels (p=0.014 and p=0.008). CETP gene TaqIB polymorphism B2B2
      genotype was associated with high level of HDL cholesterol and a more favorable
      lipid profile. 

PMID- 25073459
TI  - Inequity in the Face of Death.
AB  - We apply the theory of inequality of opportunity to the measurement of inequity
      in mortality. Using a rich data set linking records of mortality and health
      events to survey data on lifestyles for the Netherlands (1998-2007), we test the
      sensitivity of estimated inequity to different normative choices and conclude
      that the location of the responsibility cut is of vital importance. Traditional
      measures of inequity (such as socioeconomic and regional inequalities) only
      capture part of more comprehensive notions of unfairness. We show that
      distinguishing between different routes via which variables might be associated
      to mortality is essential to the application of different normative positions.
      Using the fairness gap (direct unfairness), measured inequity according to our
      implementation of the 'control' and 'preference' approaches ranges between 0.0229
      and 0.0239 (0.0102-0.0218), while regional and socioeconomic inequalities are
      smaller than 0.0020 (0.0001). The usual practice of standardizing for age and
      gender has large effects on measured inequity. Finally, we use our model to
      measure inequity in simulated counterfactual situations. While it is a big
      challenge to identify all causal relationships involved in this empirical
      context, this does not affect our main conclusions regarding the importance of
      normative choices in the measurement of inequity. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 25073460
TI  - Unwritten rules: virtual bargaining underpins social interaction, culture, and
      society.
AB  - Many social interactions require humans to coordinate their behavior across a
      range of scales. However, aspects of intentional coordination remain puzzling
      from within several approaches in cognitive science. Sketching a new perspective,
      we propose that the complex behavioral patterns - or 'unwritten rules' -
      governing such coordination emerge from an ongoing process of 'virtual
      bargaining'. Social participants behave on the basis of what they would agree to
      do if they were explicitly to bargain, provided the agreement that would arise
      from such discussion is commonly known. Although intuitively simple, this
      interpretation has implications for understanding a broad spectrum of social,
      economic, and cultural phenomena (including joint action, team reasoning,
      communication, and language) that, we argue, depend fundamentally on the virtual
      bargains themselves. 

PMID- 25073461
TI  - Molecular properties of the high-affinity choline transporter CHT1.
AB  - This article summarizes molecular properties of the high-affinity choline
      transporter (CHT1) with reference to the historical background focusing studies
      performed in laboratories of the author. CHT1 is present on the presynaptic
      terminal of cholinergic neurons, and takes up choline which is the precursor of
      acetylcholine. The Na(+)-dependent uptake of choline by CHT1 is the rate-limiting
      step for synthesis of acetylcholine. CHT1 is the integral membrane protein with
      13 transmembrane segments, belongs to the Na(+)/glucose co-transporter family
      (SLC5), and has 20-25% homology with members of this family. A single nucleotide
      polymorphism (SNP) for human CHT1 has been identified, which has a replacement
      from isoleucine to valine in the third transmembrane segment and shows the
      choline uptake activity of 50-60% as much as that of wild-type CHT1. The
      proportion of this SNP is high among Asians. Possible importance of choline diet
      for those with this SNP was discussed. 

PMID- 25073462
TI  - Royal Jelly-Mediated Prolongevity and Stress Resistance in Caenorhabditis elegans
      Is Possibly Modulated by the Interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3
      Proteins.
AB  - Recent studies suggest that royal jelly (RJ) and its related substances may have
      antiaging properties. However, the molecular mechanisms underlying the beneficial
      effects remain elusive. We report that the effects of RJ and enzyme-treated RJ
      (eRJ) on life span and health span in Caenorhabditis elegans (C elegans) are
      modulated by the sophisticated interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3
      proteins. Dietary supplementation with RJ or eRJ increased C. elegans life span
      in a dose-dependent manner. The RJ and eRJ consumption increased the tolerance of
      C elegans to oxidative stress, ultraviolet irradiation, and heat shock stress.
      Our genetic analyses showed that RJ/eRJ-mediated life-span extension requires
      insulin/IGF-1 signaling and the activities of DAF-16, SIR-2.1, HCF-1, and FTT-2,
      a 14-3-3 protein. Earlier studies reported that DAF-16/FOXO, SIR-2.1/SIRT1, FTT
      2, and HCF-1 have extensive interplays in worms and mammals. Our present findings
      suggest that RJ/eRJ-mediated promotion of longevity and stress resistance in C
      elegans is dependent on these conserved interplays. From an evolutionary point of
      view, this study not only provides new insights into the molecular mechanisms of
      RJ's action on health span promotion in C elegans, but also has imperative
      implications in using RJ/eRJ as nutraceuticals to delay aging and age-related
      disorders. 

PMID- 25073464
TI  - Modeling and validating the cost and clinical pathway of colorectal cancer.
AB  - BACKGROUND: Cancer is a major cause of morbidity and mortality, and colorectal
      cancer (CRC) is the third most common cancer in the world. The estimated costs of
      CRC treatment vary considerably, and if CRC costs in a model are based on
      empirically estimated total costs of stage I, II, III, or IV treatments, then
      they lack some flexibility to capture future changes in CRC treatment. The
      purpose was 1) to describe how to model CRC costs and survival and 2) to validate
      the model in a transparent and reproducible way. METHODS: We applied a semi
      Markov model with 70 health states and tracked age and time since specific health
      states (using tunnels and 3-dimensional data matrix). The model parameters are
      based on an observational study at Oslo University Hospital (2049 CRC patients),
      the National Patient Register, literature, and expert opinion. The target
      population was patients diagnosed with CRC. The model followed the patients
      diagnosed with CRC from the age of 70 until death or 100 years. The study focused
      on the perspective of health care payers. RESULTS: The model was validated for
      face validity, internal and external validity, and cross-validity. The validation
      showed a satisfactory match with other models and empirical estimates for both
      cost and survival time, without any preceding calibration of the model.
      CONCLUSIONS: The model can be used to 1) address a range of CRC-related themes
      (general model) like survival and evaluation of the cost of treatment and
      prevention measures; 2) make predictions from intermediate to final outcomes; 3)
      estimate changes in resource use and costs due to changing guidelines; and 4)
      adjust for future changes in treatment and trends over time. The model is
      adaptable to other populations.

PMID- 25073463
TI  - Radiologic and clinicopathologic findings of peripheral primitive neuroectodermal
      tumors.
AB  - BACKGROUND: Primitive neuroectodermal tumors (PNETs) constitute a rare type of
      malignant neuroectodermal tumors that have chromosomal translocations identical
      to Ewing's sarcoma (ES), and the characteristics of this disease remain unclear.
      PURPOSE: To describe the clinical, radiological, and pathological features of
      peripheral PNETs (pPNETs) to enhance their recognition. MATERIAL AND METHODS: The
      clinical, imaging, and pathologic findings of 35 patients with pPNETs were
      retrospectively reviewed, all being confirmed by biopsy or surgical pathology.
      All 35 patients had preoperative computed tomography (CT) examinations; 10
      patients had preoperative magnetic resonance imaging (MRI) studies. RESULTS: Of
      35 pPNET patients, 54.3% had a primary tumor in soft tissue, the others in bone.
      On plain CT images, 33 lesions demonstrated heterogeneous hypodense masses with
      multiple lamellar lower density, and with osteolytic destruction if the tumor
      originated in bone. Calcification was only found in five lesions arising in soft
      tissue. All lesions enhanced heterogeneously with varying areas of cystic
      changes, and all lesions in bone and 52.6% of lesions in soft tissue showed ill
      defined margins after contrast administration. On MRI, these tumors appeared in
      conjunction with osteolytic bone destruction and irregular soft tissue masses iso
      to hypointense to skeletal muscle on T1-weighted images and showed
      heterogeneously high intensity on T2-weighted images. All lesions enhanced
      heterogeneously with cystic changes. Homer-Wright rosettes were observed in 15
      lesions, and 97.1% lesions were positive for CD99 in histopathological results.
      CONCLUSION: pPNETs can involve any part of the body, and a large, ill-defined,
      aggressive soft tissue mass and heterogeneous enhancement with or without
      osteolytic bone destruction on CT or MR images could suggest the diagnosis.

PMID- 25073465
TI  - Origin of the European avian-like swine influenza viruses.
AB  - The avian-like swine influenza viruses emerged in 1979 in Belgium and Germany.
      Thereafter, they spread through many European swine-producing countries, replaced
      the circulating classical swine H1N1 influenza viruses, and became endemic.
      Serological and subsequent molecular data indicated an avian source, but details
      remained obscure due to a lack of relevant avian influenza virus sequence data.
      Here, the origin of the European avian-like swine influenza viruses was analysed
      using a collection of 16 European swine H1N1 influenza viruses sampled in 1979
      1981 in Germany, the Netherlands, Belgium, Italy and France, as well as several
      contemporaneous avian influenza viruses of various serotypes. The phylogenetic
      trees suggested a triple reassortant with a unique genotype constellation. Time
      resolved maximum clade credibility trees indicated times to the most recent
      common ancestors of 34-46 years (before 2008) depending on the RNA segment and
      the method of tree inference.

PMID- 25073466
TI  - Antibiotic prophylaxis reduced symptomatic urinary tract infection in children
      with vesicoureteral reflux, but not scarring.

PMID- 25073468
TI  - Serological survey of Leishmania infection in blood donors in Salvador,
      Northeastern Brazil.
AB  - BACKGROUND: Visceral Leishmaniasis is endemic to Brazil, where it is caused by
      Leishmania infantum (syn. Leishmania chagasi). Following parasite inoculation,
      individuals may experience asymptomatic infection, raising the possibility of
      parasite transmission through the transfusion of contaminated blood products. In
      the present work, we evaluated the prevalence of asymptomatic Leishmania
      infection among blood donors in Salvador, northeastern Brazil. METHODS:
      Peripheral blood was collected from 700 blood donors attending the Blood Bank of
      Bahia (HEMOBA/SESAB), from January to September 2010. We evaluated anti
      Leishmania serology by ELISA, employing Soluble Leishmania Antigen (sensitivity
      90% and specificity 95%). The presence of parasite DNA was determined by qPCR,
      targeting a single copy gene (G6PD), and by end-point PCR, targeting multiple
      targets, namely a segment located in the Leishmania rRNA locus (ITS) and the
      conserved region of kinetoplastid DNA (kDNA) minicircles. RESULTS: The blood
      donor population was comprised of 74.5% of males with a mean age of 34 years.
      Anti-Leishmania serology by ELISA was positive in 5.4% (38/700) individuals. One
      individual was also positive for Chagas' disease and another tested positive for
      Syphilis. Employing qPCR, parasite DNA was not found in any of 38 seropositive
      samples. However, by ITS PCR, 8/38 (21%) samples were positive and this
      positivity increased to 26/38 (68%) when we targeted kDNA amplification.
      Agreement between both techniques (ITS and kDNA PCR) was fair (kappa = 0.219).
      CONCLUSIONS: These results indicate that asymptomatic infection is present among
      the blood donor population of Salvador, a finding that warrants a broader
      discussion regarding the need to implement specific screening strategies.

PMID- 25073470
TI  - GP commissioners not spending enough on mental health, claims Labour.

PMID- 25073469
TI  - Levels and distribution of self-rated health in the Kazakh population: results
      from the Kazakhstan household health survey 2012.
AB  - BACKGROUND: The high and fluctuating mortality and rising health inequalities in
      post-Soviet countries have attracted considerable attention. However, there are
      very few individual-level data on distribution of health outcomes in Central
      Asian countries of the former Soviet Union. We analysed socioeconomic predictors
      of two self-rated health outcomes in a national survey in Kazakhstan. METHODS: We
      used data from the 2012 Kazakhstan Household Health Survey on 12,560 respondents
      aged 15+. Self-rated health, self-reported worsening of health, and a range of
      socio-demographic variables were collected in an interview. The self-rated health
      outcomes were dichotomized and logistic regression was used to estimate their
      associations with education, income, ownership of a car, second house and
      computer, marital status, ethnicity and urban/rural residence. RESULTS: The
      prevalence of poor/very poor self-rated health was 5.3%, and 11.0% of
      participants reported worse health compared to 1 year ago. After controlling for
      age, sex and region, all socio-demographic factors were related to self-rated
      health. After adjusting for all variables, education and car ownership showed the
      most consistent effects; the odds ratio of poor health and worsening of health
      were 0.43 (95% confidence interval 0.32-0.58) and 0.54 (0.44-0.68) for university
      vs. primary education, respectively, and 0.64 (0.51-0.82) and 0.68 (0.58-0.80)
      for car ownership, respectively. Unmarried persons, ethnic Russians and urban
      residents also had increased prevalence of poor health in multivariable models.
      CONCLUSIONS: Despite the limitations of using subjective health measures, these
      data suggest strong associations between two measures of self-rated health and a
      number of socioeconomic characteristics. Future studies and health policy
      initiatives in Kazakhstan and other Central Asian countries should take social
      determinants of health into account.

PMID- 25073471
TI  - Respondent-driven sampling to assess outcomes of sexual violence: a
      methodological assessment.
AB  - Sexual violence is pervasive in eastern Democratic Republic of Congo (DRC).
      Survivors of sexual violence encounter numerous challenges, and women with a
      sexual violence-related pregnancy (SVRP) face even more complex sequelae. Because
      of the stigma associated with SVRP, there is no conventional sampling frame and,
      therefore, a paucity of research on SVRP outcomes. Respondent-driven sampling
      (RDS), used to study this "hidden" population, uses a peer recruitment sampling
      system that maintains strict participant privacy and controls and tracks
      recruitment. If RDS assumptions are met and the sample attains equilibrium,
      sample weights to correct for biases associated with traditional chain referral
      sampling can be calculated. Questionnaires were administered to female
      participants who were raising a child from a SVRP and/or who terminated a SVRP. A
      total of 852 participants were recruited from October 9, 2012, to November 7,
      2012. There was rapid recruitment, and there were long referral chains. The
      majority of the variables reached equilibrium; thus, trends established in the
      sample population reflected the target population's trends. To our knowledge,
      this is the first study to use RDS to study outcomes of sexual violence. RDS was
      successfully applied to this population and context and should be considered as a
      sampling methodology in future sexual violence research. 

PMID- 25073472
TI  - Maternal genitourinary infections and the risk of gastroschisis.
AB  - Genitourinary infections (GUIs) have been associated with increased risk of
      gastroschisis in 2 studies. Using data collected in the Slone Epidemiology Center
      Birth Defects Study, we examined the association between GUI and gastroschisis.
      From 1998 to 2010, mothers of 249 gastroschisis cases and 7,104 controls were
      interviewed within 6 months of delivery about pregnancy events, including vaginal
      infections, genital herpes, urinary tract infections (UTIs), and other sexually
      transmitted diseases (STDs). Women were considered exposed if they reported at
      least 1 instance of a GUI in the first trimester. Logistic regression models were
      used to calculate odds ratios and 95% confidence intervals. Women who reported
      having any GUI had an adjusted odds ratio of 1.8 (95% confidence interval (CI):
      1.3, 2.4). The highest risk was seen among women who reported a UTI only
      (adjusted odds ratio = 2.3, 95% CI: 1.5, 3.5), while the odds ratio for an STD
      only was slightly elevated (adjusted odds ratio = 1.2, 95% CI: 1.0, 1.5). Among
      women under 25 years of age, the odds ratio for UTI only was 2.6 (95% CI: 1.7,
      4.0), and among older women it was 1.8 (95% CI: 0.6, 5.9). When we considered the
      joint association of UTIs and young maternal age, a synergistic effect was
      observed. The results of this study add further evidence that UTIs may increase
      the risk of gastroschisis. 

PMID- 25073473
TI  - Translational pharmacokinetic-pharmacodynamic modeling for an orally available
      novel inhibitor of anaplastic lymphoma kinase and c-Ros oncogene 1.
AB  - An orally available macrocyclic small molecule, PF06463922 [(10R)-7-amino-12
      fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4
      (metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile], is
      a selective inhibitor of anaplastic lymphoma kinase (ALK) and c-Ros oncogene 1
      (ROS1). The objectives of the present study were to characterize the
      pharmacokinetic-pharmacodynamic relationships of PF06463922 between its systemic
      exposures, pharmacodynamic biomarker (target modulation), and pharmacologic
      response (antitumor efficacy) in athymic mice implanted with H3122 non-small cell
      lung carcinomas expressing echinoderm microtubule-associated protein-like 4
      (EML4)-ALK mutation (EML4-ALK(L1196M)) and with NIH3T3 cells expressing CD74
      ROS1. In these nonclinical tumor models, PF06463922 was orally administered to
      animals with EML4-ALK(L1196M) and CD74-ROS1 at twice daily doses of 0.3-20 and
      0.01-3 mg/kg per dose, respectively. Plasma concentration-time profiles of
      PF06463922 were adequately described by a one-compartment pharmacokinetic model.
      Using the model-simulated plasma concentrations, a pharmacodynamic indirect
      response model with a modulator sufficiently fit the time courses of target
      modulation (i.e., ALK phosphorylation) in tumors of EML4-ALK(L1196M)-driven
      models with EC50,in vivo of 36 nM free. A drug-disease model based on an indirect
      response model reasonably fit individual tumor growth curves in both EML4
      ALK(L1196M)- and CD74-ROS1-driven models with the estimated tumor stasis
      concentrations of 51 and 6.2 nM free, respectively. Thus, the EC60,in vivo (52 nM
      free) for ALK inhibition roughly corresponded to the tumor stasis concentration
      in an EML4-ALK(L1196M)-driven model, suggesting that 60% ALK inhibition would be
      required for tumor stasis. Accordingly, we proposed that the EC60,in vivo for ALK
      inhibition corresponding to the tumor stasis could be considered a minimum target
      efficacious concentration of PF06463922 for cancer patients in a phase I trial. 

PMID- 25073474
TI  - The molecular mechanism of intestinal levodopa absorption and its possible
      implications for the treatment of Parkinson's disease.
AB  - Levodopa (L-DOPA) is the naturally occurring precursor amino acid for dopamine
      and the main therapeutic agent for neurologic disorders due to dopamine
      depletion, such as Parkinson's disease. l-DOPA absorption in small intestine has
      been suggested to be mediated by the large neutral amino acids transport
      machinery, but the identity of the involved transporters is unknown. Clinically,
      coadministration of l-DOPA and dietary amino acids is avoided to decrease
      competition for transport in intestine and at the blood-brain barrier. l-DOPA is
      routinely coadministered with levodopa metabolism inhibitors (dopa-decarboxylase
      and cathechol-O-methyl transferase inhibitors) that share structural similarity
      with levodopa. In this systematic study involving Xenopus laevis oocytes and
      Madin-Darby canine kidney epithelia expression systems and ex vivo preparations
      from wild-type and knockout mice, we identified the neutral and dibasic amino
      acids exchanger (antiporter) b(0,+)AT-rBAT (SLC7A9-SLC3A1) as the luminal
      intestinal l-DOPA transporter. The major luminal cotransporter (symporter)
      B(0)AT1 (SLC6A19) was not involved in levodopa transport. L-Leucine and L
      arginine competed with levodopa across the luminal enterocyte membrane as
      expected for b(0,+)AT-rBAT substrates, whereas dopa-decarboxylase and cathechol-O
      methyl transferase inhibitors had no effect. The presence of amino acids in the
      basolateral compartment mimicking the postprandial phase increased
      transepithelial levodopa transport by stimulating basolateral efflux via the
      antiporter LAT2-4F2 (SLC7A8-SLC3A2). Additionally, the aromatic amino acid
      uniporter TAT1 (SLC16A10) was shown to play a major role in l-DOPA efflux from
      intestinal enterocytes. These results identify the molecular mechanisms mediating
      small intestinal levodopa absorption and suggest strategies for optimization of
      delivery and absorption of this important prodrug. 

PMID- 25073475
TI  - MutaCYP: Classification of missense mutations in human cytochromes P450.
AB  - BACKGROUND: Cytochrome P450 monooxygenases (CYPs) represent a large and diverse
      family of enzymes involved in various biological processes in humans. Individual
      genome sequencing has revealed multiple mutations in human CYPs, and many
      missense mutations have been associated with variety of diseases. Since 3D
      structures are not resolved for most human CYPs, there is a need for a reliable
      sequence-based prediction that discriminates benign and disease causing
      mutations. METHODS: A new prediction method (MutaCYP) has been developed for
      scoring de novo missense mutations to have a deleterious effect. The method
      utilizes only five features, all of which are sequence-based: predicted relative
      solvent accessibility (RSA), variance of predicted RSA among the residues in
      close sequence proximity, Z-score of Shannon entropy for a given position,
      difference in similarity scores and weighted difference in size between wild type
      and new amino acids. The method is based on a single neural network. RESULTS:
      MutaCYP achieves MCC = 0.70, Q2 = 88.52%, Recall = 93.40% with Precision =
      91.09%, and AUC = 0.909. Comparative evaluation with other existing methods
      indicates that MutaCYP outperforms SIFT and PolyPhen-2. Predictions by MutaCYP
      appear to be orthogonal to predictions by the evaluated methods. Potential issues
      on reliability of annotations of mutations in the existing databases are
      discussed. CONCLUSIONS: A new accurate method, MutaCYP, for classification of
      missense mutations in human CYPs is presented. The prediction model consists of
      only five sequence-based features, including a real-valued predicted relative
      solvent accessibility. The method is publicly available at
      http://research.cchmc.org/MutaSense/.

PMID- 25073467
TI  - Bile acid signaling in metabolic disease and drug therapy.
AB  - Bile acids are the end products of cholesterol catabolism. Hepatic bile acid
      synthesis accounts for a major fraction of daily cholesterol turnover in humans.
      Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary
      secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine,
      bile acids are essential for the absorption, transport, and metabolism of dietary
      fats and lipid-soluble vitamins. Extensive research in the last 2 decades has
      unveiled new functions of bile acids as signaling molecules and metabolic
      integrators. The bile acid-activated nuclear receptors farnesoid X receptor,
      pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G
      protein-coupled bile acid receptor play critical roles in the regulation of
      lipid, glucose, and energy metabolism, inflammation, and drug metabolism and
      detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is
      entrained by fasting and refeeding as well as nutrient status and plays an
      important role for maintaining metabolic homeostasis. Recent research revealed an
      interaction of liver bile acids and gut microbiota in the regulation of liver
      metabolism. Circadian disturbance and altered gut microbiota contribute to the
      pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty
      liver disease, diabetes, and obesity. Bile acids and their derivatives are
      potential therapeutic agents for treating metabolic diseases of the liver. 

PMID- 25073476
TI  - Hooking up and psychological well-being in college students: short-term
      prospective links across different hookup definitions.
AB  - Hooking up (sex outside committed, romantic relationships) is feared to result
      from or lead to compromised psychological well-being among undergraduates, yet
      longitudinal evidence is scarce and inconclusive, and different hookup
      definitions complicate cross-study comparisons. This study examined short-term
      longitudinal associations with four well-being indicators (depression, anxiety,
      life satisfaction, and self-esteem) across several definitions of hookups based
      on relationship length (one time, longer casual, and any) and physical intimacy
      level (kissing, genital touching, oral sex, and intercourse). A university-wide
      sample of 666 Northeastern U.S. freshmen and juniors (63% female, 68% White)
      completed online surveys at the beginning and end of one academic semester.
      Linear and logistic regressions explored whether hookups over the semester were
      linked to later well-being, and whether initial well-being was linked to later
      hookups. Across all 96 regressions, statistically significant associations
      between well-being and hookups were infrequent (23%), predominantly confined to
      anxiety and life satisfaction, equally likely in the direction of higher (13%) as
      lower (10%) well-being, and affected by both casual relationship length and
      intimacy level. When gender differences emerged (11%), hookups were associated
      with higher well-being for women and lower well-being for men. This complex set
      of results points to the importance of researchers' choices in hookup
      definitions. 

PMID- 25073478
TI  - How should a follicular adenoma with papillary architecture be classified on
      thyroid FNA? Case report with histological correlation.

PMID- 25073477
TI  - Striatal serotonin 2C receptors decrease nigrostriatal dopamine release by
      increasing GABA-A receptor tone in the substantia nigra.
AB  - Drugs acting at the serotonin-2C (5-HT2C) receptor subtype have shown promise as
      therapeutics in multiple syndromes including obesity, depression, and Parkinson's
      disease. While it is established that 5-HT2C receptor stimulation inhibits DA
      release, the neural circuits and the localization of the relevant 5-HT2C
      receptors remain unknown. This study used dual-probe in vivo microdialysis to
      investigate the relative contributions of 5-HT2C receptors localized in the rat
      substantia nigra (SN) and caudate-putamen (CP) in the control of nigrostriatal DA
      release. Systemic administration (3.0 mg/kg) of the 5-HT2C receptor selective
      agonist Ro 60-0175 [(alphaS)-6-Chloro-5-fluoro-alpha-methyl-1H-indole-1
      ethanamine fumarate] decreased, whereas intrastriatal infusions of the selective
      5-HT2C antagonist SB 242084 [6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3
      pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide; 1.0 MUM] increased, basal
      DA in the CP. Depending on the site within the SN pars reticulata (SNpr),
      infusions of SB 242084 had more modest but significant effects. Moreover,
      infusions of the GABA-A receptor agonist muscimol (10 MUM) into the SNpr
      completely reversed the increases in striatal DA release produced by
      intrastriatal infusions of SB 242084. These findings suggest a role for 5-HT2C
      receptors regulating striatal DA release that is highly localized. 5-HT2C
      receptors localized in the striatum may represent a primary site of action that
      is mediated by the actions on GABAergic activity in the SN. Dopamine (DA) neurons
      in the substantia nigra pars compacta (SNpc) project to the caudate-putamen (CP;
      striatum). This circuitry is implicated in numerous pathologies including
      Parkinson's disease. Using in vivo microdialysis, we demonstrated that blockade
      of serotonin (5-HT) 2C receptors in the CP increased nigrostriatal DA release.
      Infusions of a GABA-A agonist into the substantia nigra pars reticulata (SNpr)
      blocked this increase. This work indicates that striatal serotonin 2C receptors
      regulate GABAergic tone in the SNpr, which in turn regulates nigrostriatal DA
      release. 

PMID- 25073479
TI  - What factors influence concordance with medications? Findings from the U.K. Asian
      Diabetes study.
AB  - AIMS: To investigate concordance with medication, as assessed at baseline and at
      1- and 2-year follow-up, and to examine factors associated with non-concordance
      in a UK-resident South-Asian population. METHODS: Data from the UK Asian Diabetes
      Study were analysed. Concordance with medications was assessed and recorded at
      three time points during the study. Multiple logistic regression was used to
      investigate the factors associated with non-concordance; the associations of
      baseline factors with year 1 concordance and baseline plus year 1 factors with
      year 2 concordance. RESULTS: Data for 403 patients from seven practices
      participating in the UK Asian Diabetes Study were analysed. The numbers of
      patients who were non-concordant were: 63 (16%) at baseline; 101 (25%) at year 1;
      and 122 (30%) at year 2. The baseline-measured variables that were significantly
      associated with year 1 non-concordance included diabetes duration, history of
      cardiovascular disease, components of the EuroQol quality of life questionnaire,
      the EQ-5D score, and number of medications prescribed. In multivariable analyses,
      the most important determinant of year 1 non-concordance was baseline non
      concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of
      medications prescribed for blood pressure control was also significant: odds
      ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for
      year 2 non-concordance. CONCLUSIONS: Non-concordance with medications was common
      and more likely in people prescribed more medications. The current target-driven
      management of risk factor levels may lead to increasing numbers and doses of
      medications. Considering the high cost of medications and the implications of
      poor health behaviours on morbidity and mortality, further investigation of
      prescribing behaviours and the factors affecting patient concordance are
      required.

PMID- 25073480
TI  - Comparative analyses of host responses upon infection with moderately virulent
      classical swine fever virus in domestic pigs and wild boar.
AB  - BACKGROUND: Classical swine fever (CSF) is one of the most important viral
      diseases of pigs. Clinical signs may vary from almost inapparent infection to a
      hemorrhagic fever like illness. Among the host factors leading to different
      disease courses are age, breed, and immune status. The aim of this study was to
      compare host responses of different pig breeds upon infection with a recent
      moderately virulent CSF virus (CSFV) strain, and to assess their impact on the
      clinical outcome and the efficiency of immune responses. To this means, two
      domestic pig types (German Landrace and hybrids), were compared to European wild
      boar. Along with clinical and pathological assessments and routine virological
      and serological methods, kinetics of immune-cellular parameters were evaluated.
      FINDINGS: All animals were susceptible to infection and despite clinical
      differences, virus could be detected in all infected animals to similar amounts.
      All but one animal developed an acute disease course, two landrace animals
      recovered after a transient infection. One wild boar got chronically infected.
      Changes in the percentages of lymphocyte subsets in peripheral blood did not show
      a clear correlation with the clinical outcome. High and early titers of
      neutralizing antibodies were especially detected in wild boar and German Landrace
      pigs. CONCLUSIONS: While differences among breeds did not have the expected
      impact on course and outcome of CSFV infection, preload with facultative
      pathogens and even small differences in age seemed to be more relevant. Future
      studies will target the characterization of responses observed during different
      disease courses including cytokine reactions and further analyses of lymphocyte
      subsets.

PMID- 25073481
TI  - Non-immune-related genes and signalling pathways in spleen of Vibrio
      parahaemolyticus-infected Epinephelus fuscoguttatus (Forskal).

PMID- 25073482
TI  - Evaluation of thoracic limb loads, elbow movement, and morphology in dogs before
      and after arthroscopic management of unilateral medial coronoid process disease.
AB  - OBJECTIVE: To (1) evaluate thoracic limb loads and symmetry, and elbow function
      and morphology, before and after arthroscopic treatment of unilateral medial
      coronoid process disease (MCPD), and (2) determine if functional variables
      correlate with morphologic findings. STUDY DESIGN: Prospective case series.
      ANIMALS: Dogs (n = 14) with thoracic limb lameness. METHODS: Dogs were included
      when unilateral MCPD was confirmed as the cause of lameness. Kinetic analysis of
      both thoracic limbs, along with kinematic analysis and goniometry of both elbows
      were carried out before, and 60, 120, and 180 days after partial coronoidectomy
      by arthroscopy. Radiography and computed tomography of both elbows were performed
      before and 180 days after arthroscopy. RESULTS: A nonsignificant (P = .11)
      increase in the peak vertical loads (PFz), and a significant (P = .022) increase
      in the vertical impulse (iFz) applied by the affected limb were seen. Symmetry
      indices improved, with significant differences between sessions (PFz: P = .019;
      iFz: P = .003). Kinematic variables showed no significant differences, between
      sessions or when comparing both elbows within sessions. Goniometry revealed no
      significant differences between sessions, but some significant differences were
      identified when comparing both elbows within sessions. Osteophytosis and degree
      of lameness showed no correlation, before (rs  = -0.077; P = .79) or after
      arthroscopy (rs  = 0.27; P = .35). CONCLUSIONS: Kinetic variables improved after
      arthroscopy, without full restoration of function. Kinematic variables did not
      change significantly. Osteoarthritis and goniometric measurements in the affected
      joint worsened. Functional variables did not correlate with morphologic findings.

PMID- 25073483
TI  - Influence of dietary protein level on body composition and energy expenditure in
      calorically restricted overweight cats.
AB  - High-protein (HP) diets help prevent loss of lean mass in calorie-restricted (CR)
      cats. However, it is not entirely known whether these diets also induce changes
      of energy expenditure during periods of CR. To investigate this issue, sixteen
      overweight cats were fed either a high-protein [(HP), 54.2% of metabolizable
      energy (ME)] or a moderate-protein [(MP), 31.5% of ME] diet at 70% of their
      maintenance energy intakes for 8 weeks, and energy expenditure, energy intake,
      body weight and composition, and serum metabolites and hormones were measured.
      While both groups of cats lost weight at a similar rate, only cats eating the HP
      diet maintained lean mass during weight loss. Indirect respiration calorimetry
      measurements revealed that both total and resting energy expenditure (kcal/d)
      significantly decreased during weight loss for both treatment groups. However,
      only cats eating the MP diet exhibited significant decreases of total and resting
      energy expenditures after energy expenditure was normalized for body weight or
      lean mass. Results from this study suggest that in addition to sparing the loss
      of lean mass, feeding HP diets to overweight cats in restricted amounts may be
      beneficial for preventing or minimizing decreases of mass-adjusted energy
      expenditure during weight loss.

PMID- 25073484
TI  - Disfiguring papular sarcoidosis of the face: dramatic improvement with
      pimecrolimus.

PMID- 25073485
TI  - 1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1
      transcription.
AB  - BACKGROUND AND PURPOSE: HIV-1 transcription is activated by the Tat protein which
      recruits the cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. Tat binds to
      protein phosphatase-1 (PP1) through the Q(35) VCF(38) sequence and translocates
      PP1 to the nucleus. PP1 dephosphorylates CDK9 and activates HIV-1 transcription.
      We have synthesized a low MW compound 1H4, that targets PP1 and prevents HIV-1
      Tat interaction with PP1 and inhibits HIV-1 gene transcription. Here, we report
      our further work with the 1H4-derived compounds and analysis of their mechanism
      of action. EXPERIMENTAL APPROACH: Using the 1H4-PP1 complex as a model, we
      iteratively designed and synthesized follow-up libraries that were analysed for
      the inhibition of HIV-1 transcription and toxicity. We also confirmed the
      mechanism of action of the PP1-targeting molecules by determining the affinity of
      binding of these molecules to PP1, by analysing their effects on PP1 activity,
      disruption of PP1 binding to Tat and shuttling of PP1 to the nucleus. KEY
      RESULTS: We identified a tetrahydroquinoline derivative, compound 7, which
      disrupted the interaction of Tat with PP1. We further optimized compound 7 and
      obtained compound 7c, renamed 1E7-03, which inhibited HIV-1 with low IC50
      (fivefold lower than the previously reported compound, 1H4), showed no
      cytotoxicity and displayed a plasma half-life greater than 8 h in mice. 1E7-03
      bound to PP1 in vitro and prevented shuttling of PP1 into the nucleus.
      CONCLUSIONS AND IMPLICATIONS: Our study shows that low MW compounds that
      functionally mimic the PP1-binding RVxF peptide can inhibit HIV-1 transcription
      by deregulating PP1.

PMID- 25073487
TI  - High performance ZnO-SnO2:F nanocomposite transparent electrodes for energy
      applications.
AB  - Enhancing the propagation length of light without sacrificing the electro-optical
      properties of transparent electrodes is of particular interest to solar cells for
      reaching higher efficiency. This can typically be achieved by nanostructured
      electrodes but all too often at the expense of complexity and cost-effectiveness.
      In this work, we demonstrate the simple and low-cost fabrication of a new type of
      ZnO-SnO2:F nanocomposite thin film by combining spin-coated ZnO nanoparticles on
      glass with fluorine-doped SnO2 thin films deposited by atmospheric spray
      pyrolysis. The resulting nanocomposites exhibit a dual surface morphology
      featuring rough ZnO-SnO2:F nanostructures along with the original smooth SnO2:F
      thin film. By readily modulating the surface morphology of ZnO-SnO2:F
      nanocomposite thin films with the initial ZnO NP surface coverage, the scattering
      efficiency of the incident light can remarkably be controlled over the 400-1100
      nm solar spectrum wavelength range. High quality hazy ZnO-SnO2:F thin layers are
      therefore formed with an averaged haze factor ranging from 0.4 to 64.2% over the
      400-1100 nm solar spectrum range while the sheet resistance is kept smaller than
      15 Omega/sq for an average total optical transmittance close to 80%, substrate
      absorption and reflection included. Eventually, optical simulations using Fourier
      transform techniques are performed for computing the obtained haze factors and
      show good agreement with experimental data in the 400-1100 nm solar spectrum
      wavelength range. This opens up additional opportunities for further design
      optimization of nanoengineered transparent electrodes. 

PMID- 25073486
TI  - Women's preferences for inpatient and outpatient priming for labour induction: a
      discrete choice experiment.
AB  - BACKGROUND: In many countries a high proportion of births begin as induced
      labours. Induction can be lengthy if cervical priming is required prior to
      induction. This usually occurs as an inpatient, however, an alternative is to
      allow women to go home after satisfactory fetal monitoring. The aim of this study
      was to assess the preferences of women for cervical priming for induction of
      labour in an outpatient or inpatient setting. METHOD: A discrete choice
      experiment (DCE) was conducted alongside a randomised trial of inpatient and
      outpatient cervical priming (the OPRA trial) in two maternity hospitals in South
      Australia. 362 participants were included, and women's preferences for cervical
      priming for induction of labour were assessed. RESULTS: Women were willing to
      accept an extra 1.4 trips to hospital (2.4 trips total) and a total travel time
      of 73.3 minutes to be able to return to their own home while waiting for the
      priming to work. For enhanced inpatient services, women were willing to accept a
      total travel time of 54.7 minutes to have a private room with private bathroom
      while waiting for the priming to work. The overall benefit score for outpatient
      priming was 3.63, 3.59 for enhanced inpatient care and 2.89 for basic inpatient
      care, suggesting slightly greater preferences for outpatient priming. Preferences
      for outpatient priming increased when women could return to their own home
      (compared to other offsite accommodation), and decreased with more trips to
      hospital and longer travel time. CONCLUSIONS: Our results suggest that outpatient
      priming was slightly more preferred than either enhanced inpatient priming or
      basic care; these results should be confirmed in different clinical settings.
      There may be merit in providing women information about both options in the
      future, as preferences varied according to the characteristics of the services on
      offer and the sociodemographic background of the woman.

PMID- 25073488
TI  - Nonlinear optical absorption in a graphene infrared photodetector.
AB  - The photoresponse of the graphene photodetector elucidated strong dependence on
      several optical parameters, such as the angle of incidence and the incident power
      of infrared exposure at room temperature. The sinusoidal dependence of the
      photoresponse on incidence angle, which had not been realized before, has now
      been revealed. The combined effect of the photo excited charge carrier and the
      photon drag effect explain this nonlinear optical absorption in graphene at lower
      incident power. The nonlinear dependence of the charge carrier generation on the
      incident power revealed that this process contributed to the nonlinear
      photoresponse. However, a deviation is observed at a higher incident power due to
      the induction of thermal effects in the graphene lattice. This work demonstrates
      the tunability of the graphene photodetector under a systematic variation that
      involves both parameters. 

PMID- 25073489
TI  - Prevalence of constipation in a tertiary referral Italian Colorectal Unit.
AB  - INTRODUCTION: Epidemiology data on constipation are not commonly available,
      particularly in Italy Here we review the prevalence and clinical features of
      constipated patients attending a tertiary referral Italian center. METHODS:
      Clinical data of patients attending our Coloproctology Unit in the last 15 years
      and complaining of constipation as the main clinical features were
      retrospectively analyzed. Rome-III criteria were adoptedto define constipation.
      RESULTS: 1041/11881 patients were affected by chronic constipation (8.8%), 376
      had slow-transit constipation, 497 obstructed defecation and 168 both types of
      constipation. 76% of them were females. Patients distribution according to sex
      and age was Gaussian-like only in females. In the slow-transit group,
      constipation was idiopathic in 59.3% and secondary to other causes in 40.7% . In
      patients with anatomic obstructed defecation, rectocele and intussusceptions were
      the main findings, while pelvic floor dissynergia was the main finding in
      functional outlet obstruction, although more frequently all these components were
      associated. In 14.8% no apparent cause was identified. CONCLUSION: Constipation
      accounts for about 9% of patients attending a tertiary referral Colorectal Unit.
      Females were much more frequently affected in both types of constipation.
      Anatomic and functional defecatory disturbances are frequently associated,
      although in 15% no evident causes were identified. KEY WORDS: Constipation,
      Epidemiology, Obstructed defecation, Slow transit constipation.

PMID- 25073491
TI  - Simultaneous trial of deep brain and motor cortex stimulation in chronic
      intractable neuropathic pain.
AB  - BACKGROUND/OBJECTIVES: Both motor cortex stimulation (MCS) and deep brain
      stimulation (DBS) of the ventralis caudalis (Vc) thalamus have been shown to be
      effective in chronic neuropathic pain, and the modulation of thalamic and
      thalamocortical activity is regarded as a possible mechanism. Although Vc DBS and
      MCS have a common analgesic mechanism, the application of MCS and DBS is still
      considered empirical, and there is no consensus on which method is better.
      METHODS: We performed a simultaneous trial of thalamic Vc DBS and MCS in 9
      patients with chronic neuropathic pain and investigated the results of the
      stimulation trial and long-term pain relief. RESULTS: Of the 9 patients initially
      implanted with both DBS and MCS electrodes, 8 (89%) had a successful trial; 6 of
      these 8 patients (75%) responded to MCS, and the remaining 2 responded to Vc DBS.
      During the long-term follow-up, the mean numeric rating scale score decreased
      significantly (p < 0.05). The percentages of pain relief in the chronic MCS group
      and the chronic DBS group were 37.9 +/- 16.5 and 37.5%, respectively, and there
      was no statistically significant difference (p = 0.157). CONCLUSION: Considering
      the initial success rate and the less invasive nature of epidural MCS compared
      with DBS, we think that MCS would be a more reasonable initial means of treatment
      for chronic intractable neuropathic pain.

PMID- 25073490
TI  - Cardiac surgery for patients with heart failure due to structural heart disease
      in Uganda: access to surgery and outcomes.
AB  - OBJECTIVE: Few data are available on heart failure (HF) in sub-Saharan Africa. We
      aimed to provide a current picture of HF aetiologies in urban Uganda, access to
      heart surgery, and outcomes. METHODS: We prospectively collected clinical and
      echocardiographic data from 272 consecutive patients referred for suspected heart
      disease to a tertiary hospital in Kampala during seven non-governmental
      organisation (NGO) missions from 2009 to 2013. We focused the analysis on 140
      patients who fulfilled standardised criteria of HF by echocardiography. RESULTS:
      Rheumatic heart disease (RHD) was the leading cause of HF in 44 (31%) patients.
      Among the 50 children included (age <= 16 years), congenital heart disease (CHD)
      was the first cause of HF (30 patients, 60%), followed by RHD (16 patients, 32%).
      RHD was the main cause of HF (30%) among the 90 adults. All 85 patients with RHD
      and CHD presented with an indication for heart surgery, of which 74 patients were
      deemed fit for intervention. Surgery was scheduled in 38 patients with RHD [86%,
      median age 19 years (IQR: 12-31)] and in 36 patients with CHD [88%, median age 4
      years (IQR 1-5)]. Twenty-seven candidates (32%) were operated on after a median
      waiting time of 10 months (IQR 6-21). Sixteen (19%) had died after a median of 38
      months (IQR 5-52); 19 (22%) were lost to follow up. CONCLUSION: RHD still
      represents the leading cause of HF in Uganda, in spite of cost-efficient
      prevention strategies. The majority of surgical candidates, albeit young, do not
      have access to treatment and present high mortality rates.

PMID- 25073493
TI  - Lactobezoar formation in two premature infants receiving medium-chain
      triglyceride formula.
AB  - We describe two cases of premature infants who developed clinical and radiologic
      evidence of gastric lactobezoars within the same month in our neonatal intensive
      care unit while both were receiving medium-chain triglyceride-rich formula as
      part of the management of chylothoraces. 

PMID- 25073494
TI  - Early vitamin K deficiency bleeding in a neonate associated with maternal Crohn's
      disease.
AB  - We report herein a case of early vitamin K deficiency bleeding (VKDB) in a
      neonate associated with maternal Crohn's disease. A female neonate was born at 37
      weeks' gestation and weighed 2778 g. She developed broad purpura on her back on
      day 1. Laboratory data showed anemia, prolonged coagulation time and elevated
      protein induced by vitamin K absence or antagonist-II. Early VKDB has not been
      reported in a neonate born from mother with active Crohn's disease. It is
      essential to give vitamin K selectively as soon as possible after birth to
      prevent early VKDB in neonates.

PMID- 25073495
TI  - Hypomagnesemia secondary to cerebrospinal fluid losses in a patient with
      congenital hydrocephalus.
AB  - We describe a newborn infant with massive congenital hydrocephalus, presenting
      with hypomagnesemia secondary to magnesium losses through cerebrospinal fluid
      (CSF) aspirations. Hypomagnesemia due to CSF losses has not been described in
      pediatric literature. 

PMID- 25073496
TI  - Paradoxical downward seizure pattern on amplitude-integrated
      electroencephalogram.
AB  - The use of amplitude-integrated electroencephalography (aEEG) to assess brain
      function and detect seizures has been increasing worldwide. Results from previous
      studies have demonstrated that seizure patterns can be recognized as transient
      rises on aEEG traces. We report here a case of an infant with neonatal seizures
      that showed paradoxical transient drops on aEEG traces. The ictal EEG showed
      initial low-amplitude fast rhythmic activity followed by epileptic recruiting
      rhythms and high-voltage slow waves. Therefore, downward patterns on aEEG traces
      should be recognized as suspected seizure patterns. 

PMID- 25073497
TI  - Monochorionic-monoamniotic twins discordant for VATER association.
AB  - We describe a monozygotic twin discordant for VATER association with single
      dysplastic kidney and cloacal anomaly, who had no pulmonary hypoplasia. This twin
      probably had little or no urine output in utero, but still had normal lung
      development due to production of adequate amniotic fluid by the healthy twin
      preventing pulmonary hypoplasia. The discordance between monozygotic twins for
      VATER association indicates that factors other than inherited genetic ones may
      have a role in the causation of this association. 

PMID- 25073498
TI  - Neonatal presentation of posterior urethral valves and tethered spinal cord.

PMID- 25073499
TI  - Is anterior placentation per se a risk for cesarean section-related morbidity in
      placenta previa?

PMID- 25073500
TI  - Response to Baba et al.

PMID- 25073501
TI  - NICU handoff lacks completion.

PMID- 25073502
TI  - Response to Catlin.

PMID- 25073503
TI  - Extent of flood damage increased cerebrovascular disease incidences in Iwate
      prefecture after the great East Japan earthquake and tsunami of 2011.
AB  - BACKGROUND: Several studies have reported on increases in the incidence of
      cardiovascular and cerebrovascular diseases after huge earthquakes. An increase
      in the incidence of cerebrovascular diseases was observed after the Great East
      Japan Earthquake and Tsunami of 2011. To assess whether tsunami damage or the
      earthquake was responsible for this trend, we assessed the relative impact of
      earthquake magnitude and flood damage on cerebrovascular disease. METHODS: A
      total of 12 coastal municipalities facing the epicenter were divided into 4 flood
      severity groups according to the percentage of people living in the flooded areas
      (<20, 20-40, 40-60, and >=60%) and 3 groups according to the Japanese
      Meteorological Agency seismic intensity of the main shock (<4.5, 4.5-5.0 and
      >=5.0). The standard incidence ratios (SIRs) of cerebrovascular diseases in the
      first 4 weeks after the disaster compared with the same periods in 2008-2010 were
      calculated for each flood severity group and each earthquake severity group. Odds
      ratios (ORs) of disease incidence and the adjusted ORs for seismic intensity
      (using the Mantel-Haenszel method) between the higher (>=40%) and the lower
      flooded area (<40%) were compared with the same periods in 2008-2010. Likewise,
      ORs and adjusted ORs for flood severity in the high seismic intensity area
      (>=4.9) were compared with those in the low seismic intensity area (<4.9).
      RESULTS: SIRs increased with the increased flood severity: 0.94 (0.59-1.30) at
      <20%, 1.02 (0.70-1.34) at 20-40%, 1.26 (0.66-1.86) at 40-60% and 1.98 (1.25-2.72)
      at >=60%. However, SIRs did not increase with increased seismic intensity: 0.95
      (0.60-1.29) at <4.5, 1.52 (1.07-1.98) at 4.5-5.0 and 1.17 (0.80-1.54) at >=5.0.
      ORs and adjusted ORs for seismic intensity in the high flood area compared with
      the low flood area were significant: 1.68 (1.07-2.65) and 1.78 (1.08-2.96),
      respectively. However, ORs and adjusted ORs for flood severity in the high
      seismic intensity area compared with the low intensity area were not significant:
      1.33 (0.82-2.17) and 1.19 (0.62-2.31), respectively. CONCLUSIONS: Cerebrovascular
      disease incidences after the Great East Japan Earthquake and Tsunami of 2011
      increased because of tsunami damage and not because of the earthquake magnitude.

PMID- 25073504
TI  - Functional optoacoustic imaging of moving objects using microsecond-delay
      acquisition of multispectral three-dimensional tomographic data.
AB  - The breakthrough capacity of optoacoustics for three-dimensional visualization of
      dynamic events in real time has been recently showcased. Yet, efficient spectral
      unmixing for functional imaging of entire volumetric regions is significantly
      challenged by motion artifacts in concurrent acquisitions at multiple
      wavelengths. Here, we introduce a method for simultaneous acquisition of
      multispectral volumetric datasets by introducing a microsecond-level delay
      between excitation laser pulses at different wavelengths. Robust performance is
      demonstrated by real-time volumetric visualization of functional blood
      parametrers in human vasculature with a handheld matrix array optoacoustic probe.
      This approach can avert image artifacts imposed by velocities greater than 2 m/s,
      thus, does not only facilitate imaging influenced by respiratory, cardiac or
      other intrinsic fast movements in living tissues, but can achieve artifact-free
      imaging in the presence of more significant motion, e.g. abrupt displacements
      during handheld-mode operation in a clinical environment.

PMID- 25073505
TI  - Phosphoinositides and engulfment.
AB  - Cellular engulfment of particles, cells or solutes displaces large domains of
      plasma membrane into intracellular membranous vacuoles. This transfer of membrane
      is accompanied by major transitions of the phosphoinositide (PI) species that
      comprise the cytoplasmic face of membrane bilayers. Mapping of membrane PIs
      during engulfment reveals distinct patterns of protein and PI distributions
      associated with each stage of engulfment, which correspond with activities that
      regulate the actin cytoskeleton, membrane movements and vesicle secretion.
      Experimental manipulation of PI chemistry during engulfment indicates that PIs
      integrate organelle identity and orient signal transduction cascades within
      confined subdomains of membrane. These pathways are exploited by microbial
      pathogens to direct or redirect the engulfment process.

PMID- 25073506
TI  - Cortical thinning, functional connectivity, and mood-related impulsivity in
      schizophrenia: relationship to aggressive attitudes and behavior.
AB  - OBJECTIVE: Aggression in schizophrenia is a major societal issue, leading to
      physical harm, stigmatization, patient distress, and higher health care costs.
      Impulsivity is associated with aggression in schizophrenia, but it is
      multidetermined. The subconstruct of urgency is likely to play an important role
      in this aggression, with positive urgency referring to rash action in the context
      of positive emotion, and negative urgency referring to rash action in the context
      of negative emotion. METHOD: The authors examined urgency and its neural
      correlates in 33 patients with schizophrenia or schizoaffective disorder and 31
      healthy comparison subjects. Urgency was measured using the Urgency,
      Premeditation, Perseverance, and Sensation-Seeking scale. Aggressive attitudes
      were measured using the Buss-Perry Aggression Questionnaire. RESULTS: Positive
      urgency, negative urgency, and aggressive attitudes were significantly and
      selectively elevated in schizophrenia patients (Cohen's d values, 1.21-1.50).
      Positive and negative urgency significantly correlated with the Aggression
      Questionnaire total score (r>0.48 in all cases) and each uniquely accounted for a
      significant portion of the variance in aggression over and above the effect of
      group. Urgency scores correlated with reduced cortical thickness in ventral
      prefrontal regions including the right frontal pole, the medial and lateral
      orbitofrontal gyrus and inferior frontal gyri, and the rostral anterior cingulate
      cortex. In patients, reduced resting-state functional connectivity in some of
      these regions was associated with higher urgency. CONCLUSIONS: These findings
      highlight the key role of urgency in aggressive attitudes in people with
      schizophrenia and suggest neural substrates of these behaviors. The results also
      suggest behavioral and neural targets for interventions to remediate urgency and
      aggression.

PMID- 25073507
TI  - Compound heterozygous CORO1A mutations in siblings with a mucocutaneous
      immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum
      contagiosum and granulomatous tuberculoid leprosy.
AB  - PURPOSE: Coronin-1A deficiency is a recently recognized autosomal recessive
      primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results
      in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined
      immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus
      the defining characteristics are not well delineated. We identified a unique
      CORO1A-kindred. METHODS: We captured a 10-year analysis of the immune-clinical
      phenotypes in two affected siblings from disease debut of age 7 years. Target
      specific genetic studies were pursued but unrevealing. Telomere lengths were also
      assessed. Whole exome sequencing (WES) uncovered the molecular diagnosis and
      Western blot validated findings. RESULTS: We found the compound heterozygous
      CORO1A variants: c.248_249delCT (p.P83RfsX10) and a novel mutation c.1077delC
      (p.Q360RfsX44) (NM_007074.3) in two affected non-consanguineous siblings that
      manifested as absent CD4CD45RA(+) (naive) T and memory B cells, low NK cells and
      abnormally increased double-negative (DN) Upsilondelta T-cells. Distinguishing
      characteristics were late clinical debut with an unusual mucocutaneous syndrome
      of epidermodysplasia verruciformis-human papilloma virus (EV-HPV), molluscum
      contagiosum and oral-cutaneous herpetic ulcers; the older female sibling also had
      a disfiguring granulomatous tuberculoid leprosy. Both had bilateral
      bronchiectasis and the female died of EBV+ lymphomas at age 16 years. The younger
      surviving male, without malignancy, had reproducibly very short telomere lengths,
      not before appreciated in CORO1A mutations. CONCLUSION: We reveal the third
      CORO1A-mutated kindred, with the immune phenotype of abnormal naive CD4 and DN T
      cells and newfound characteristics of a late/hypomorphic-like SCID of an EV-HPV
      mucocutaneous syndrome with also B and NK defects and shortened telomeres. Our
      findings contribute to the elucidation of the CORO1A-SCID-CID spectrum.

PMID- 25073508
TI  - Ezrin silencing remodulates the expression of Phosphoinositide-specific
      Phospholipase C enzymes in human osteosarcoma cell lines.
AB  - Ezrin, a protein belonging to the Ezrin, radixin and moesin (ERM) family, was
      engaged in the metastatic spread of osteosarcoma. The Protein 4.1, Ezrin,
      radixin, moesin (FERM) domain of Ezrin binds the membrane Phosphatydil inositol
      (4,5) bisphosphate (PIP2), a crucial molecule belonging to the Phosphoinositide
      (PI) signal transduction pathway. The cytoskeleton cross-linker function of Ezrin
      largely depends on membrane PIP2 levels, and thus upon the activity of related
      enzymes belonging to the PI-specific phospholipase C (PI-PLC) family. Based on
      the role of Ezrin in tumour progression and metastasis, we silenced the
      expression of Vil2 (OMIM *123900), the gene which codifies for Ezrin, in cultured
      human osteosarcoma 143B and Hs888 cell lines. After Ezrin silencing, the growth
      rate of both cell lines was significantly reduced and morphogical changes were
      observed. We also observed moderate variations both of selected PI-PLC enzymes
      within the cell and of expression of the corresponding PLC genes. In 143B cell
      line the transcription of PLCB1 decreased, of PLCG2 increased and of PLCE
      differed in a time-dependent manner. In Hs888, the expression of PLCB1 and of
      PLCD4 significantly increased, of PLCE moderately increased in a time dependent
      manner; the expression of PLCG2 was up-regulated. These observations indicate
      that Ezrin silencing affects the transcription of selected PLC genes, suggesting
      that Ezrin might influence the expression regulation of PI-PLC enzymes. 

PMID- 25073509
TI  - Oxygen differentially affects the hox proteins Hoxb5 and Hoxa5 altering airway
      branching and lung vascular formation.
AB  - Hoxb5 and Hoxa5 transcription factor proteins uniquely impact lung morphogenesis
      at the developmental time point when extremely preterm infants are born. The
      effect of O2 exposure (0.4 FiO2) used in preterm infant care on these Hox
      proteins is unknown. We used ex vivo fetal mouse lung organ cultures to explore
      the effects of 0.4 FiO2 on lung airway and vascular formation in the context of
      Hoxb5 and Hoxa5 expression and regulation. Compared to room air, 48 h (h) 0.4
      FiO2 adversely attenuated airway and microvasculature formation while reducing
      lung growth and epithelial cell volume, and increasing mesenchymal volume. 0.4
      FiO2 decreased pro-angiogenic Hoxb5 and VEGFR2 while not altering protein levels
      of angiostatic Hoxa5. Lungs returned to RA after 24 h 0.4FiO2 had partial
      structural recovery but remained smaller and less developed. Mesenchymal cell
      apoptosis increased and proliferation decreased with time in O2 while epithelial
      cell proliferation significantly increased. Hoxb5 overexpression led to prominent
      peri-airway VEGFR2 expression and promoted lung vascular and airway patterning.
      Hoxa5 overexpression had the opposite effects. We conclude that 0.4 FiO2 exposure
      causes a profound loss of airway and lung microvascular development that occurs
      partially via reduction in pro-angiogenic Hoxb5 while angiostatic Hoxa5
      expression is maintained. 

PMID- 25073511
TI  - miR-24 promotes the proliferation and invasion of HCC cells by targeting SOX7.
AB  - Accumulating evidence shows that microRNAs (miRNAs) are involved in the
      development and progression of multiple tumors, including hepatocellular
      carcinoma (HCC). Recent studies have found that miR-24 acts as an oncogene in
      several tumors; however, the function of miR-24 in HCC remains unclear. In this
      study, we found that miR-24 was increased in HCC tissues and cell lines.
      Inhibition of miR-24 by inhibitor significantly suppressed HCC cells
      proliferation, migration, and invasion. Furthermore, the sex-determining region Y
      (SRY)-box 7 (SOX7), a putative tumor suppressor, was found to be a target of miR
      24 in HCC cells. Forced expression of SOX7 substantially attenuated the oncogenic
      effects of miR-24. Those results strongly suggest that miR-24 plays important
      role in HCC development partially by targeting SOX7. 

PMID- 25073510
TI  - miR-144 suppresses the proliferation and metastasis of hepatocellular carcinoma
      by targeting E2F3.
AB  - MicroRNAs (miRNAs) play essential roles in the progression of hepatocellular
      carcinoma (HCC). miR-144 acts as a tumor suppressor in some malignancies, while
      its role in HCC is unclear. Here, we found that miR-144 was significantly
      decreased in HCC tissues and cell lines. Forced overexpression of miR-144
      remarkably reduced cell proliferation, increased apoptosis, and suppressed
      migration and invasion of HCC cells. E2F transcription factor 3 (E2F3) was
      identified as a target of miR-144 in HCC cells. Moreover, E2F3 overexpression
      partially attenuated the tumor suppressive effects of miR-144, and the expression
      of E2F3 was negatively correlated with miR-144 level in HCC tissues. Our data
      suggest that miR-144 might suppress the growth and motility of HCC cells
      partially by targeting E2F3. 

PMID- 25073512
TI  - Fenofibrate enhances radiosensitivity of esophageal squamous cell carcinoma by
      suppressing hypoxia-inducible factor-1alpha expression.
AB  - Radiation therapy is widely used in esophageal squamous cell carcinoma (ESCC).
      Promoting radiation sensitivity is important. Recent studies have shown that
      fenofibrate can inhibit the growth of several cancer lines and hypoxia-inducible
      factor-1alpha (HIF-1alpha) expression in MCF-7 cells. However, few studies on the
      radiosensitive effect of fenofibrate on ESCCs under hypoxic condition have been
      conducted. In this study, we assessed the radiosensitive effects of fenofibrate
      on human ESCC cells. In vitro experiments showed the inhibition of cytotoxic
      effects after ionizing irradiation. We measured cell viability and clonogenic
      survival rate. Flow cytometry showed that fenofibrate pretreatment promoted
      apoptosis. The in vivo data also suggest that fenofibrate had radiosensitizing
      effects in ECA-109 cells xenografted into nude mice. Western blot and
      immunohistochemical analyses revealed that the HIF-1alpha and vascular
      endothelial growth factor (VEGF) protein content decreased by fenofibrate. Thus,
      the inhibition of HIF-1alpha and VEGF expression in ESCC cells contributed to the
      radiosensitive effect. These data suggest that fenofibrate may be a potential
      radiosensitive drug. 

PMID- 25073513
TI  - Effect of lycopene isolated from Chlorella marina on proliferation and apoptosis
      in human prostate cancer cell line PC-3.
AB  - Even though the role of lycopene from tomato (trans form) in controlling prostate
      cancer was reported, lycopene (cis and trans 60:40) isolated from green algae
      Chlorella marina was not reported so far. The present study aimed to assess the
      anti-proliferative and apoptotic effect of lycopene from a new source and to
      compare the activity with available trans lycopene by using androgen-independent
      human prostate cancer cell lines. Exposure of PC-3 and DU-145 cell lines to algal
      lycopene (AL) at a dose of 20 and 50 MUM significantly inhibited the growth and
      colony formation, and the percentage of inhibition was higher than tomatal
      lycopene (TL)-treated groups. The stability of AL in cell culture medium was
      high, when compared to TL under standard cell culture conditions. The level of
      lycopene was not detected in PC-3 cell lines cultured in medium lacking lycopene.
      Staining cells with acridine orange and ethidium bromide, the PC-3 control cells
      showed largely non-fragmented intact nucleoid. Stronger apoptosis signal was
      induced with higher concentrations (50 MUM) of algal lycopene. Increased DNA
      damage was observed in AL- and TL-treated cells which appear as comet during
      single-cell gel electrophoresis. Flow cytometry results revealed that AL caused
      PC-3 cells to accumulate in the G0/G1 phase and to undergo apoptosis. The effect
      was higher in AL groups than TL-treated groups. Algal lycopene showed very
      significant anti-proliferative and apoptotic effect in human prostate cancer cell
      lines. Therefore, algal lycopene from C.marina would be recommended for the
      treatment of prostate cancer.

PMID- 25073514
TI  - NBS1 Glu185Gln polymorphism and susceptibility to urinary system cancer: a meta
      analysis.
AB  - A number of studies have investigated the association between the NBS1 Glu185Gln
      (rs1805794, 8360 G>C) polymorphism and risk for urinary system cancer including
      bladder cancer, prostate cancer, and renal cell cancer; however, the findings are
      conflicting. We conducted a meta-analysis focusing on eight published studies
      with 3,542 cases and 4,210 controls to derive a more precise evaluation of the
      relationship between the NBS1 Glu185Gln polymorphism and urinary system cancer
      susceptibility. Overall, the NBS1 Glu185Gln polymorphism was significantly
      related to increased risk for urinary system cancer (homozygous model: odds ratio
      (OR)=1.23, 95 % confidence interval (95% CI)= 1.05-1.44, p=0.011; heterozygous
      model: OR=1.14, 95% CI=1.04-1.26, p=0.008; dominant model: OR=1.16, 95% CI=1.05
      1.27, p=0.002; and Gln vs. Glu: OR=1.12, 9% CI=1.04-1.20, p=0.002) and further
      stratification analysis indicated an increased risk for bladder cancer
      (heterozygous model: OR=1.13, 95% CI=1.02-1.26, p=0.022; dominant model: OR=1.14,
      95% CI=1.03-1.26, p=0.014; and Gln vs. Glu: OR=1.09, 95%CI=1.01-1.18, p=0.023)
      and Caucasian populations (homozygous model: OR=1.33, 95% CI=1.11-1.59, p=0.002;
      heterozygous model: OR=1.16, 95% CI=1.04-1.30, p=0.009; dominant model: OR=1.19,
      95% CI=1.07-1.32, p=0.001; and Gln vs. Glu: OR=1.15, 95% CI=1.06-1.25, p<0.001).
      Despite some limitations, this meta-analysis established some solid statistical
      evidence for the association between NBS1 Glu185Gln polymorphism and increased
      risk for urinary system cancer, especially for bladder cancer, but more well
      designed prospective studies are needed to further verify our findings.

PMID- 25073515
TI  - Circulating levels and clinical implications of epithelial membrane antigen and
      cytokeratin-1 in women with breast cancer: can their ratio improve the results?
AB  - Immunohistochemical studies proved that the presence of breast cancer (BrCa) is
      accompanied by elevated levels of epithelial membrane antigen (EMA) and decreased
      levels of cytokeratin-1 (CK1). We, therefore, hypothesize that the serum EMA/CK1
      ratio may serve as a promising biomarker for early diagnosis of breast cancer.
      The circulating levels of EMA and CK1 were determined by Western blot and enzyme
      linked immunosorbent assay (ELISA) in sera from 102 women with BrCa and 90 women
      as controls (40 with benign breast disease and 50 healthy). EMA at 130 kDa and
      CK1 at 67 kDa were identified, purified, and quantified in sera of BrCa patients
      using ELISA. EMA/CK1 ratio values were found to discriminate BrCa patients from
      controls (P < 0.0001) with high diagnostic ability (area under the curve [AUC] =
      0.901, sensitivity = 82, specificity = 76). The sensitivity and specificity for
      early-stage (<= T2) BrCa were 72 and 76%, respectively. The ratio values of
      patients with late-stage (>T2) tumors were significantly higher than those of
      patients with early-stage (<= T2) tumors. Moreover, higher grades (grades 2-3)
      were associated with higher values than grade 1 tumors. AUC values in different
      BrCa patients who had early stage, low grade, or size <= 2 cm were 0.855, 0.762,
      and 0.839, respectively. AUC values of patients with positive lymph node or
      positive distant metastasis were 0.907 and 0.913, respectively. We show for the
      first time the impact of serum EMA and CK1 ratio in BrCa detection. Differential
      EMA/CK1 values may serve as a diagnostic marker in early-stage breast cancer
      patients.

PMID- 25073516
TI  - Meta-analysis of genome-wide association study of homeostasis model assessment
      beta cell function and insulin resistance in an East Asian population and the
      European results.
AB  - Compared with Western populations, Asians develop diabetes at younger ages, at
      lower degrees of obesity. Because diabetes and the related traits are influenced
      by the interplay between genetic and environmental factors, it is important to
      understand the genetic differences between Asian and Western populations.
      Recently, a large-scale meta-analysis of genome-wide association studies for beta
      cell function and insulin resistance in the European ancestry was reported by the
      Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). The MAGIC
      study reported 17 SNPs for homeostasis model assessments (HOMA-%B: beta cell
      function and HOMA-IR: insulin resistance). In this study, we tried to replicate
      the effects of reported SNPs by MAGIC study, which were influencing HOMAs in two
      Korean populations. HOMA-IR and HOMA-B were computed using two HOMA models (HOMA1
      and HOMA2). The HOMA2 model has recently been updated with physiological
      adjustments into a computer version, providing a more accurate index. Dupuis et
      al. (Nat Genet 42: 105-116, 2010). In this study, we examined the reported SNPs
      in two Korean community-based cohorts (Ansung and Ansan). The Korean genotypes
      and glucose and insulin traits for 5,974 non-diabetic subjects were obtained from
      a previous genome-wide association study. Although we expected the HOMA2 to be
      suitable to replicate the results of different ethnics, our results revealed that
      the HOMA1 was more significantly replicated. As a result, 5 SNPs (rs10830963 in
      MTNR1B, rs4607517 in GCK, rs2191349 in DGKB/TMEM195, rs174550 in FADS1, rs7034200
      in GLIS3) were significantly replicated with HOMA-%B, but no SNP was replicated
      with HOMA-IR. Two SNPs (rs560887 in G6PC, rs13266634 in SLC30A8) and one SNP
      (rs35767 in IGF1) showed the weak association p values (unadjusted p values lower
      than 0.05) for HOMA-%B and HOMA-IR, respectively. The replicated SNPs and the
      weakly associated SNPs were also significantly associated with the fasting
      glucose levels. They revealed the same direction of the effect sizes in both
      studies, but the effect sizes were stronger in Koreans than in MAGIC.
      Conclusively, our results indicated that SNPs from MTNR1B, GCK, DGKB, FADS1, and
      GLIS3 were consistently associated with HOMA-%B in both Korean and MAGIC
      populations. 

PMID- 25073517
TI  - Change Trajectories: Children's Patterns of Improvement in Acute-Stay Inpatient
      Care.
AB  - This study estimated classes of children's acute-stay psychiatric acuity
      trajectories in terms of shape (i.e., linear, quadratic, cubic) and rate of
      change (slope). A total of 788 children served on three child units (ages 4-12)
      were studied. The Children's Acuity of Psychiatric Illness (CAPI) was completed
      each weekday by trained frontline staff on the milieu. Latent class growth
      analysis was applied to the data, and seven acuity trajectory classes provided
      the most parsimonious fit. Four classes evidenced a significant quadratic term,
      one class a significant linear term, and two classes did not evidence a
      significant change in acuity. The classes varied in survival time to
      rehospitalization, in pre-treatment community service use and rates of seclusion,
      restraint, and emergency medications during the episode. Overall, the results
      suggest that acute-stay patients may have distinct and identifiable psychiatric
      acuity change patterns during their episodes and that some may experience non
      linear (i.e., quadratic) acuity trajectories. 

PMID- 25073518
TI  - Biotechnological production of chiral organic sulfoxides: current state and
      perspectives.
AB  - Chiral organic sulfoxides (COSs) are important compounds that act as chiral
      auxiliaries in numerous asymmetric reactions and as intermediates in chiral drug
      synthesis. In addition to their optical resolution, stereoselective oxidation of
      sulfides can be used for COS production. This reaction is facilitated by
      oxygenases and peroxidases from various microbial resources. To meet the current
      demand for esomeprazole, a proton pump inhibitor used in the treatment of gastric
      acid-related disorders, and the (S)-isomer of an organic sulfoxide compound,
      omeprazole, a successful biotechnological production method using a Baeyer
      Villiger monooxygenase (BVMO), was developed. In this review, we summarize the
      recent advancements in COS production using biocatalysts, including enzyme
      identification, protein engineering, and process development. 

PMID- 25073519
TI  - Antibacterial activity of silver nanoparticle-coated fabric and leather against
      odor and skin infection causing bacteria.
AB  - We present a simple, eco-friendly synthesis of silver and gold nanoparticles
      using a natural polymer pine gum solution as the reducing and capping agent. The
      pine gum solution was combined with silver nitrate (AgNO3) or a chloroauric acid
      (HAuCl4) solution to produce silver nanoparticles (AgNPs) and gold nanoparticles
      (AuNPs), respectively. The reaction process was simple; formation of the
      nanoparticles was achieved by autoclaving the silver and gold ions with the pine
      gum. UV-Vis spectra showed surface plasmon resonance (SPR) for silver and gold
      nanoparticles at 432 and 539 nm, respectively. The elemental forms of AgNPs and
      AuNPs were confirmed by energy-dispersive X-ray spectroscopy (EDX). Fourier
      transform infrared spectroscopy (FTIR) showed the biomolecules present in the
      pine gum, AgNPs, and AuNPs. Transmission electron microscopy (TEM) images showed
      the shape and size of AgNPs and AuNPs. The crystalline nature of synthesized
      AgNPs and AuNPs was confirmed by X-ray crystallography [X-ray diffraction (XRD)].
      Application of synthesized AgNPs onto cotton fabrics and leather, in order to
      evaluate their antibacterial properties against odor- or skin infection-causing
      bacteria, is also discussed. Among the four tested bacteria, AgNP-coated cotton
      fabric and leather samples displayed excellent antibacterial activity against
      Brevibacterium linens.

PMID- 25073520
TI  - Maxillary molar intrusion with zygomatic anchorage in open bite treatment:
      lateral and oblique cephalometric evaluation.
AB  - PURPOSE: We aimed to use lateral and oblique radiographs to evaluate dental and
      skeletal changes arising from maxillary molar intrusion with zygomatic anchorage
      in open bite patients. METHODS: We conducted a pilot study including nine
      patients (six females and three males; mean age, 18.7 +/- 5.1 years) with
      skeletal open bite treated with titanium miniplates for posterior dentoalveolar
      intrusion. Lateral and oblique (right and left, 45 degrees ) radiographs were
      obtained before (T1) and 6 months after intrusion (T2). A paired t test was used
      for statistical evaluation. RESULTS: The maxillary posterior teeth were intruded
      2.03 +/- 0.87 mm (p < 0.01) with 450*g of force, which resulted in
      counterclockwise rotation of the mandible (1.57 degrees , p = 0.02) and clockwise
      rotation of the occlusal plane (4.27 +/- 2.66 degrees , p = 0.01). Anterior
      facial height decreased by a mean of 1.79 +/- 1.51 mm (p < 0.01). No significant
      change in the palatal plane or in anteroposterior molar movement was observed.
      CONCLUSION: The oblique radiograph at 45 degrees  was useful for the assessment
      of molar intrusion and anteroposterior displacement. The treatment of anterior
      open bite with skeletal anchorage provided intrusion of molars and
      counterclockwise rotation of the mandible, resulting in open bite closure.

PMID- 25073521
TI  - Testosterone down regulates the expression of Fmr-1 gene in the cerebral cortex
      of gonadectomized old male mice.
AB  - Sex steroid hormones are important modulators of synaptic plasticity underlying
      learning and memory, however, the precise molecular mechanism of their role in
      above is not well understood. Fragile X mental retardation protein is one of the
      proteins that regulate synaptic plasticity that declines during aging. Whether
      Fmr-1 gene expression is regulated by sex steroid hormones as a function of age
      is not known. To answer this, we have investigated Fmr-1 gene expression in the
      cerebral cortex of the gonadectomized- and testosterone-treated gonadectomized
      adult and old male mice. Our data reveal that Fmr-1 gene expression is
      significantly down regulated in adult mice brain, however, it is up regulated in
      old age following bilateral gonadectomy (castration). Administration of
      testosterone to castrated mice was found to reverse the effects of castration on
      Fmr-1 gene expression towards that in the Sham operated intact control old age
      mice whereas it has no effects as compared to that in Sham operated adult age
      mice. Further, to investigate the mechanism of this effect of testosterone, we
      studied interaction of trans-acting factors with Fmr-1 promoter by
      electrophoretic mobility shift assay (EMSA). The EMSA data shows formation of two
      complexes as a result of interaction of nuclear trans-acting factors with Fmr-1
      promoter, which also exhibited age- and hormone-dependent patterns which largely
      corresponded to the patterns of our expression data. Our data demonstrate that
      testosterone regulates Fmr-1 gene expression in age-dependent manner which may
      throw light on the mechanisms of age- and sex steroid hormones-dependent
      alterations in brain function.

PMID- 25073523
TI  - Acute parvovirus B19 infection in identical twins unmasking previously
      unidentified hereditary spherocytosis.
AB  - Identical Caucasian male twins, previously fit, presented 1 week apart with short
      histories of fever and lethargy. The twins were febrile at presentation with
      profound pancytopaenia and evidence of haemolysis. There was no rash or
      arthralgia. Both required multiple red cell transfusions. The twins had positive
      IgM serology for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus
      B19. EBV viral capsid antigen and Epstein-Barr nuclear antigen IgGs were also
      positive however, suggesting past EBV exposure. Parvovirus B19 DNA was detected
      from peripheral blood PCR; CMV and EBV DNA PCRs were negative. Convalescent
      serology demonstrated no evolution of the CMV serological response, that is no
      IgG to CMV developed which implies an initial non-specific polyclonal IgM
      response. The twins recovered fully over 7 days, the first with a course of
      prednisolone and the second spontaneously. They were diagnosed with hereditary
      spherocytosis on convalescent blood films. On further questioning, a family
      history of hereditary spherocytosis was eventually revealed. The twins' maternal
      grandmother was known to have the condition asymptomatically. Their mother had
      prior to this never been tested, but later bloods would reveal a compatible
      biochemical picture.

PMID- 25073522
TI  - Is there a risk of prion-like disease transmission by Alzheimer- or Parkinson
      associated protein particles?
AB  - The misfolding and aggregation of endogenous proteins in the central nervous
      system is a neuropathological hallmark of Alzheimer's disease (AD), Parkinson's
      disease (PD), as well as prion diseases. A molecular mechanism referred to as
      "nucleation-dependent aggregation" is thought to underlie this neuropathological
      phenomenon. According to this concept, disease-associated protein particles act
      as nuclei, or seeds, that recruit cellular proteins and incorporate them, in a
      misfolded form, into their growing aggregate structure. Experimental studies have
      shown that the aggregation of the AD-associated proteins amyloid-beta (Abeta) and
      tau, and of the PD-associated protein alpha-synuclein, can be stimulated in
      laboratory animal models by intracerebral (i.c.) injection of inocula containing
      aggregated species of the respective proteins. This has raised the question of
      whether AD or PD can be transmitted, like certain human prion diseases, between
      individuals by self-propagating protein particles potentially present on medical
      instruments or in blood or blood products. While the i.c. injection of inocula
      containing AD- or PD-associated protein aggregates was found to cause neuronal
      damage and clinical abnormalities (e.g., motor impairments) in some animal
      models, none of the studies published so far provided evidence for a transmission
      of severe or even fatal disease. In addition, available epidemiological data do
      not indicate a transmissibility of AD or PD between humans. The findings
      published so far on the effects of experimentally transmitted AD- or PD
      associated protein seeds do not suggest specific precautionary measures in the
      context of hemotherapy, but call for vigilance in transfusion medicine and other
      medical areas. 

PMID- 25073524
TI  - A rare Lisfranc-type injury involving dorsal dislocation of the intermediate
      cuneiform.
AB  - Lisfranc injuries occur at the tarsometatarsal joint resulting from direct or
      indirect force to the midfoot. They account for only 0.2% of all fractures, with
      diagnoses easily missed on presentation. The resultant instability is often
      associated with significant morbidity to the patient. This report describes a
      Lisfranc injury sustained by a healthy gentleman who suffered indirect trauma to
      the foot when he fell from a standing height. Plain film radiographs and CT
      revealed dorsal dislocation of the intermediate cuneiform associated with
      fractures at the base of the third and fourth metatarsals. He underwent open
      reduction and internal fixation the following day. His Foot and Ankle Disability
      Index (FADI) score improved from 16.3 1 week postoperatively to 58.7 6 months
      postoperatively. This report describes a rare injury pattern resulting from
      indirect, low-energy trauma. We provide a guide to appropriate radiological
      imaging and evaluation in the assessment of these complex injuries.

PMID- 25073525
TI  - Transvenous approach for the treatment of direct carotid cavernous fistula
      following Pipeline embolization of cavernous carotid aneurysm: a report of two
      cases and review of the literature.
AB  - Flow diverters are increasingly used for the endovascular treatment of cerebral
      aneurysms. A rare complication from flow diversion is delayed aneurysm rupture,
      which can lead to carotid-cavernous fistula (CCF) in the setting of cavernous
      carotid aneurysms (CCAs). Direct CCFs pose unique management challenges, given
      the lack of transarterial access to the fistula. We present two cases of direct
      CCFs following treatment of CCAs with the Pipeline embolization device (PED).
      Case 1 was a middle-aged patient with a symptomatic 10 mm wide-necked left CCA.
      Six weeks after PED treatment the patient developed diplopia secondary to direct
      CCF. Case 2 was a middle-aged patient with a symptomatic 17 mm left CCA treated
      with PED. One-month follow-up angiography demonstrated a direct CCF. Both
      patients underwent successful coil embolization of the CCF through a transvenous
      approach. Direct CCF formation following PED deployment for CCA is a rare
      complication. Parent vessel sacrifice may be avoided with transvenous occlusion
      of the fistula. 

PMID- 25073526
TI  - Vocal cord palsy anatomical changes and a foreign body mimicking malignancy.
AB  - A 74-year-old woman presented with a history of prolonged dysphonia, a red flag
      symptom for laryngeal cancer. Flexible nasal endoscopy revealed a lesion which
      looked suspicious for malignancy and therefore she went onto have a
      microlaryngoscopy and an attempt at biopsy. It was during this procedure that a
      foreign body was removed whole from a dilated laryngeal ventricle. We believe
      that some subtle anatomical changes caused by a pre-existing unilateral vocal
      cord palsy contributed to the impaction of this foreign body. 

PMID- 25073527
TI  - Intravitreal ranibizumab for bilateral choroidal neovascularisation in a patient
      with angioid streaks.
AB  - Angioid streaks are described as irregular lines deep into the retina, configured
      in a radiating fashion which results from breaks in Bruch's membrane. Optic nerve
      head drusen are acellular, globular deposits located within the optic nerve head.
      Angioid streaks and optic nerve head drusen may coexist in patients with
      pseudoxanthoma elasticum. Both disorders may cause choroidal neovascularisation.
      In this case report we aimed to present a 48-year-old man with pseudoxanthoma
      elasticum. The patient had bilateral choroidal neovascularisation secondary to
      angioid streaks and was treated with intravitreal ranibizumab injections. Visual
      acuity was increased and maintained at the same level during the follow-up time.
      There was no complication related to the injection. 

PMID- 25073528
TI  - Rare combination of paramolar and distomolar supernumerary teeth in a 15-year-old
      male adolescent.

PMID- 25073529
TI  - Patella dislocation following distal femoral replacement after bone tumour
      resection.
AB  - We report the case of a 16-year-old girl with patella dislocation following
      distal femur replacement for a malignant tumour. We performed a medial plication
      and lateral release procedure to treat her persistent patellar dislocation after
      distal femur replacement following malignant tumour resection. This treatment
      improved the patient's gait ability dramatically. A distal femur reconstruction
      with a total knee arthroplasty (TKA) system for tumour resection is a frequently
      performed procedure. The reported incidence of patella dislocation following
      distal femur reconstruction with a TKA is 2.3%. However, treatment procedures for
      patella dislocation following a distal femur replacement after malignant tumour
      resection have not been studied extensively. To the best of our knowledge, this
      is the first English case report about patella dislocation following distal
      femoral replacement focusing on surgical treatment. Our experience suggests that
      treatment for patella dislocation following distal femur reconstruction with a
      TKA should be considered positively. 

PMID- 25073530
TI  - Dengue shock syndrome in an infant.
AB  - Dengue is a mosquito-borne infection affecting children and adults worldwide. In
      newborn infants, the dengue virus can cause diseases, especially in infants born
      to pregnant women hospitalised with dengue or postpartum women with fever. The
      authors report a case of a term newborn infant who presented with haemodynamic
      instability and thrombocytopaenia at the age of 7 days, without a history of
      clinical dengue infection in the mother. The physical examination revealed an
      afebrile and drowsy infant with a petechial rash all over the body and ecchymosis
      on both palms and soles. The authors confirmed the diagnosis using the dengue NS1
      antigen on the first day of admission. The treatment included fluid management
      and platelet transfusion. The patient recovered well and was discharged from the
      hospital on the 10th day of hospitalisation. 

PMID- 25073531
TI  - Clinical features and management of a severe paradoxical reaction associated with
      combined treatment of Buruli ulcer and HIV co-infection.
AB  - BACKGROUND: In West and Central Africa Buruli ulcer (BU) and HIV co-infection is
      increasingly recognised and management of these two diseases combined is an
      emerging challenge for which there is little published information. In this case
      we present a severe paradoxical reaction occurring after commencing antibiotic
      treatment for BU combined with antiretroviral therapy for HIV, and describe its
      clinical features and management. This includes to our knowledge the first
      reported use of prednisolone in Africa to manage a severe paradoxical reaction
      related to BU treatment. CASE PRESENTATION: A 30 year old immunosuppressed HIV
      positive man from Cameroon developed a severe paradoxical reaction 24 days after
      commencing antibiotic treatment for BU and 14 days after commencing
      antiretroviral therapy for HIV. Oral prednisolone was successfully used to settle
      the reaction and prevent further tissue loss. The antiretroviral regimen was
      continued unchanged and the BU antibiotic treatment not prolonged beyond the
      recommended duration of 8 weeks. A second small local paradoxical lesion
      developed 8 months after starting antibiotics and settled with conservative
      treatment only. Complete healing of lesions occurred and there was no disease
      recurrence 12 months after commencement of treatment. CONCLUSIONS: Clinicians
      should be aware that severe paradoxical reactions can occur during the treatment
      of BU/HIV co-infected patients. Prednisolone was effectively and safely used to
      settle the reaction and minimize the secondary tissue damage.

PMID- 25073532
TI  - Prevalence of depression in adults with type 2 diabetes in the Basque Country:
      relationship with glycaemic control and health care costs.
AB  - BACKGROUND: The aim of the study was to estimate the prevalence of depression in
      the population diagnosed with diabetes type 2 and to test the hypothesis that the
      presence of depression in such cases was associated with a) worse glycaemic
      control, and b) higher healthcare costs. METHODS: We conducted a cross-sectional
      analysis, from 1st September 2010 to 31st August 2011, among patients with type 2
      diabetes aged 35 years and over in the Basque Country. It was identified how many
      of them had also depression. The database included administrative individual
      level information on age, sex, healthcare costs, other comorbidities, and values
      of glycaemic control (HbA1c). Deprivation index variable was used as
      socioeconomic measure and, to observe the coexistent pathologies, all the
      patients diagnoses were categorized by Adjusted Clinical Groups. We used a
      measure of association, a logistic and a linear regression for analysis. RESULTS:
      12.392 (9.8%) of type 2 diabetes patients were diagnosed with depression, being
      the prevalence 5.2% for males and 15.1% for females. This comorbidity was higher
      among the most deprived population. There was no association between the presence
      of depression and glycaemic control. We estimated that the comorbidity average
      cost per patient/year was 516? higher than in patients with just type 2 diabetes
      (P < 0.001) adjusted by the other covariates. CONCLUSIONS: We did not find any
      relationship between depression and glycaemic control in patients with type 2
      diabetes. However, the comorbidity was associated with significantly high
      healthcare costs compared to that of type 2 diabetes occurring alone, after
      adjusting by other illness. Thus, there is a need of more precise recognition,
      screening and monitoring of depression among diabetic population. Evidence-based
      treatment for depression should be included in type 2 diabetes clinical
      guidelines.

PMID- 25073533
TI  - Embedding mental health interventions in early childhood education systems for at
      risk preschoolers: an evidence to policy realist review.
AB  - BACKGROUND: Current early childhood systems of care are not geared to respond to
      the complex needs of preschoolers at risk for mental health problems in a timely,
      coordinated, multidisciplinary, and comprehensive fashion. Evidence-informed
      policy represents an opportunity for implementing prevention, promotion, and
      early intervention at the population or at-risk level. Exposure to risk factors
      as well as the presence of clinical disorders can derail the developmental
      trajectories of preschoolers, and problems may persist if left untreated. One way
      to address these multiple research-to-policy gaps are systematic reviews
      sensitive to context and knowledge user needs, such as the realist review. The
      realist review is an iterative process between research teams and knowledge users
      to build mid-level program theories in order to understand which interventions
      work best for whom and under what context. METHODS/DESIGN: The realist review
      employs five 'iterative' steps: (1) clarify scope, (2) search for evidence, (3)
      appraise primary studies and extract data, (4) synthesize the evidence, and (5)
      disseminate, implement, and evaluate evidence, to answer two research questions:
      What interventions improve mental health outcomes for preschoolers at risk for
      socio-emotional difficulties and under what circumstances do they work? and what
      are the best models of care for integrating mental health interventions within
      pre-existing early childhood education (ECE) services for at-risk children?
      Knowledge users and researchers will work together through each stage of the
      review starting with refining the questions through to decisions regarding
      program theory building, data extraction, analysis, and design of a policy
      dissemination plan. The initial questions will guide preliminary literature
      reviews, but subsequent more focused searches will be informed by knowledge users
      familiar with local needs and further building of explanatory program theories.
      DISCUSSION: Policy makers want to know what works best for whom, but are faced
      with a wide and disparate intervention literature for at-risk children. Applying
      evidence-based standards is a good start, but the chain of implementation between
      research results and how to match interventions sensitive to local context are
      ongoing challenges. TRIAL REGISTRATION: Prospero registration number:
      CRD42014007301.

PMID- 25073534
TI  - Myocardial injury in a 41-year-old male treated with methylphenidate: a case
      report.
AB  - BACKGROUND: Elevated cardiac troponin levels are consistent with the diagnosis of
      an acute coronary syndrome, but may also represent adverse drug reactions.
      Psychostimulating drugs raise both blood pressure and heart rate, and case
      reports of sudden death, stroke, and myocardial infarction have led to regulatory
      and public concern about the cardiovascular safety of these drugs. CASE
      PRESENTATION: We present a case where a 41-year-old Norwegian male with radiating
      chest pain, elevated troponins, and supraventricular tachycardia was
      hospitalized. Tentative diagnosis was acute coronary syndrome. Percutaneous
      coronary angiography, but not cardiac magnetic resonance imaging, was performed
      and medical antiplatelet treatment started. Because of an attention
      deficit/hyperactivity disorder the patient had recently increased his dose of
      methylphenidate, but still within the therapeutic dose range. Apart from
      venlafaxine, also in a therapeutic dose, the patient took no other drugs. An
      acute coronary syndrome was excluded during hospitalization, and a drug effect
      was suspected. CONCLUSIONS: When interpreting troponin results it is important to
      take into account the context of the patient's clinical presentation, including
      the possibility of adverse drug reactions. The adverse drug reaction could
      include a combination of vasospasm and/or increased oxygen demand due to
      tachycardia. This case should be borne in mind before a diagnosis of myocardial
      infarction is given, or a decision to perform invasive coronary angiography is
      made in patients that use methylphenidate or related substances. Cardiac magnetic
      resonance imaging could be of diagnostic value in such cases.

PMID- 25073535
TI  - Comparison of IGRA tests and TST in the diagnosis of latent tuberculosis
      infection and predicting tuberculosis in risk groups in Krakow, Poland.
AB  - BACKGROUND: The objective of this study was to assess the prevalence of latent
      tuberculosis infection (LTBI) in risk groups in Krakow, using the QuantiFERON-TB
      Gold In-Tube (QFT-GIT) test and the tuberculin skin test (TST); we also sought to
      assess the rate of progression to active disease over 4-5 y of follow-up.
      METHODS: QFT-GIT tests were performed on 785 subjects and the TST on 701 subjects
      from the risk groups of homeless persons, close contacts, periodic contacts, and
      residents of long-term care facilities (LTCFs), and subjects from a low risk
      group. RESULTS: In homeless persons, close contacts, periodic contacts, LTCF
      residents, and low risk persons, a positive QFT-GIT was found in 36.7%, 27.2%,
      27.0%, 21.1%, and 23.7% of subjects, respectively, while a positive TST was found
      in 55.8%, 47.4%, 47.6%, 43.2%, and 47.9%, respectively. Of 63 homeless subjects,
      5 developed active TB over 248 person-y of follow-up (incidence rate (IR) 20 per
      1000 person-y, 95% confidence interval (CI) 8.4-48.5); of 148 close contacts, 5
      developed active TB over 740 person-y of follow-up (IR 7, 95% CI 2.8-16.2); of
      145 periodic contacts, 2 developed active TB over 580 person-y of follow-up (IR
      4, 95% CI 0.9-13.8). The IR per 1000 person-y (95% CI) among subjects with a
      positive QFT-GIT was 30 (9.0-86.1) for homeless subjects, 18 (5.7-54.7) for close
      contacts, and 13 (3.2-51.3) for periodic contacts. In Poland there is no policy
      for the provision of LTBI treatment to people with a positive QFT or TST;
      therefore, the estimated rates of disease progression were analysed amongst
      untreated subjects. CONCLUSIONS: The prevalence of positive QFT-GIT and TST was
      high in the study risk groups. The best predictor of active TB in the homeless
      and close contacts groups was a positive QFT-GIT together with a positive TST.

PMID- 25073536
TI  - Colistin nephrotoxicity increases with age.
AB  - BACKGROUND: Colistin (COL) has become the backbone of the treatment of infections
      due to extensively drug-resistant (XDR) Gram-negative bacteria. The most common
      restriction to its use is acute kidney injury (AKI). METHODS: We conducted a
      retrospective cohort study to evaluate risk factors for new-onset AKI in patients
      receiving COL. The cohort consisted of 198 adults admitted to 9 referral
      hospitals between January 2010 and October 2012 and treated with intravenous COL
      for >= 72 h. Patients with no pre-existing kidney dysfunction were compared in
      terms of risk factors and outcomes of AKI graded according to the RIFLE criteria.
      Logistic regression analysis was used to identify associated risk factors.
      RESULTS: A total of 198 patients met the inclusion criteria, of whom 167 had no
      pre-existing kidney dysfunction; the mean patient age was 58.77 (+/- 18.98) y.
      Bloodstream infections (34.8%) and ventilator-associated pneumonia (32.3%) were
      the 2 most common indications for COL use. New-onset AKI developed in 46.1% of
      the patients, graded as risk (10%), injury (15%), and failure (21%). Patients
      with high Charlson co-morbidity index (CCI) scores (p = 0.001) and comparatively
      low initial glomerular filtration rate (GFR) estimations (p < 0.001) were more
      likely to develop AKI, but older age (p = 0.001; odds ratio 5.199, 95% confidence
      interval 2.684-10.072) was the major predictor in the multivariate analysis. In
      hospital recovery from AKI occurred in 58.1%, within a median of 7 days.
      CONCLUSIONS: COL-induced nephrotoxicity occurred significantly more often in
      patients older than 60 y of age and was related to low initial GFR estimations
      and high CCI scores, which were basically determined by age.

PMID- 25073537
TI  - Risk of HIV transmission from patients on antiretroviral therapy: a position
      statement from the Public Health Agency of Sweden and the Swedish Reference Group
      for Antiviral Therapy.
AB  - The modern medical treatment of HIV with antiretroviral therapy (ART) has
      drastically reduced the morbidity and mortality in patients infected with this
      virus. ART has also been shown to reduce the transmission risk from individual
      patients as well as the spread of the infection at the population level. This
      position statement from the Public Health Agency of Sweden and the Swedish
      Reference Group for Antiviral Therapy is based on a workshop organized in the
      fall of 2012. It summarizes the latest research and knowledge on the risk of HIV
      transmission from patients on ART, with a focus on the risk of sexual
      transmission. The risk of transmission via shared injection equipment among
      intravenous drug users is also examined, as is the risk of mother-to-child
      transmission. Based on current knowledge, the risk of transmission through
      vaginal or anal intercourse involving the use of a condom has been judged to be
      minimal, provided that the person infected with HIV fulfils the criteria for
      effective ART. This probably also applies to unprotected intercourse, provided
      that no other sexually transmitted infections are present, although it is not
      currently possible to fully support this conclusion with direct scientific
      evidence. ART is judged to markedly reduce the risk of blood-borne transmission
      between people who share injection equipment. Finally, the risk of transmission
      from mother to child is very low, provided that ART is started well in advance of
      delivery.

PMID- 25073538
TI  - Screening tests for hepatitis B virus, hepatitis C virus, and human
      immunodeficiency virus in blood donors: evaluation of two chemiluminescent
      immunoassay systems.
AB  - Automated chemiluminescent immunoassays (CLIAs) are useful for the detection of
      hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency
      virus 1/2 antigen/antibodies (HIV 1/2 Ag/Ab) in blood donor screening. Eight
      hundred and forty serum samples were tested for hepatitis B surface antigen
      (HBsAg), HCV antibodies (anti-HCV), and HIV1/2 Ag/Ab in parallel using 2
      different CLIAs (Abbott Architect i2000SR and Roche Cobas e411). The concordance
      between the 2 systems was high (Cohen's kappa 0.97 for HBsAg, 0.77 for anti-HCV,
      0.92 for HIV1/2 Ag/Ab) and the specificity and the positive predictive value were
      comparable. Among the 12 discrepant results, 11 were false-positive and 1
      (reactive by Architect) was true-positive for anti-HCV. Positivity for HBV DNA,
      HCV RNA, and HIV RNA was recorded in 90.9%, 38.9%, and 100% of true-positive
      samples, respectively. This study represents the first stringent comparison
      between Architect i2000SR and Cobas e411 in blood donors. We observed a good
      correlation and high agreement among HBV, HCV, and HIV with the 2 automated
      systems.

PMID- 25073539
TI  - Interstitial 10p11.23-p12.1 microdeletions associated with developmental delay,
      craniofacial abnormalities, and cryptorchidism.
AB  - Cryptorchidism is the most common genital problem encountered in males and is
      associated with many chromosomal disorders; however, the genetic factors are
      mostly unknown. To delineate critical genes affecting testicular migration, we
      performed genotype-phenotype correlation in patients with deletions involving the
      proximal short arm of chromosome 10 (10p11-p12), a rare abnormality characterized
      by developmental delay, craniofacial abnormalities, and in some cases,
      cryptorchidism. Here we report on a male patient with developmental delay, mild
      craniofacial dysmorphism, bilateral cryptorchidism, and an 850-kb deletion,
      within the 10p11.2 region, involving three genes-MKX, ARMC4, and MPP7-as
      determined by array comparative genomic hybridization analysis. Comparison with
      four previously reported male patients with overlapping deletions revealed a 140
      kb common region, containing the MKX gene, in association with cryptorchidism.
      The MKX gene is a member of the three amino acid loop extension (TALE) superclass
      of homeobox genes that is expressed in developing male gonads (male gonadal ridge
      and testis cords) in temporal relationship to SOX9, a critical regulator of
      sexual differentiation. Our results suggest that haploinsufficiency of the MKX
      gene may affect the developmental process during testis migration or serve as a
      genetic susceptibility locus for cryptorchidism. We propose that deletions of the
      proximal 10p represent a contiguous gene syndrome; therefore, patients may
      present with a complex phenotype, depending on the extent of the deletion.

PMID- 25073540
TI  - Cigarette smoke condensate inhibits collagen gel contraction and prostaglandin E2
      production in human gingival fibroblasts.
AB  - BACKGROUND: Granulation tissue remodeling and myofibroblastic differentiation are
      critically important events during wound healing. Tobacco smoking has a
      detrimental effect in gingival tissue repair. However, studies evaluating the
      effects of cigarette smoke on these events are lacking. MATERIAL AND METHODS: We
      used gingival fibroblasts cultured within free-floating and restrained collagen
      gels to simulate the initial and final steps of the granulation tissue phase
      during tissue repair. Collagen gel contraction was stimulated with serum or
      transforming growth factor-beta1. Cigarette smoke condensate (CSC) was used to
      evaluate the effects of tobacco smoke on gel contraction. Protein levels of alpha
      smooth muscle actin, beta1 integrin, matrix metalloproteinase-3 and connective
      tissue growth factor were evaluated through Western blot. Prostaglandin E(2)
      (PGE(2)) levels were determined through ELISA. Actin organization was evaluated
      through confocal microscopy. RESULTS: CSC reduced collagen gel contraction
      induced by serum and transforming growth factor-beta1 in restrained collagen
      gels. CSC also altered the development of actin stress fibers in fibroblasts
      cultured within restrained collagen gels. PGE(2) levels were strongly diminished
      by CSC in three-dimensional cell cultures. However, other proteins involved in
      granulation tissue remodeling and myofibroblastic differentiation such as alpha
      smooth muscle actin, beta1 integrin, matrix metalloproteinase-3 and connective
      tissue growth factor, were unmodified by CSC. CONCLUSIONS: CSC may alter the
      capacity of gingival fibroblasts to remodel and contract a collagen matrix.
      Inhibition of PGE(2) production and alterations of actin stress fibers in these
      cells may impair proper tissue maturation during wound healing in smokers.

PMID- 25073542
TI  - The effect of fractionated radiotherapy in sensorineural hearing loss: an animal
      model.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study is to assess the effect of
      fractionated radiotherapy on sensorineural hearing loss using an animal model.
      STUDY DESIGN: In vivo animal study. METHODS: Ears of 25 guinea pigs were divided
      into three groups: control, irradiated with a total of 48 gray (Gy), and 71 Gy.
      Unilateral exposure of 48 Gy and 71 Gy fractionated irradiation was given for a 4
      week period. Auditory brainstem response and distortion products otoacoustic
      emissions (DPOAE) were tested prior to irradiation and 1, 6, 10, and 16 weeks
      after completion of radiotherapy to assess the hearing threshold shift
      postradiotherapy over time. RESULTS: No significant differences in hearing
      thresholds between the low dose radiation (48 Gy) and the control group (no
      radiation) underlined that 48 Gy caused no hearing deficits (P = 0.37). The
      higher dose (71 Gy) showed progressive deterioration of the hearing function over
      time. Three-way ANOVA interactions revealed significant group-time effects (F=
      9.261; P < 0.0001). DPOAE analysis demonstrated hearing loss at 71 Gy without
      progression or recovery at all time points, predominantly in the higher
      frequencies tested. CONCLUSION: The present study suggests that in the presence
      of sensorineural hearing loss due to high- dose fractionated radiotherapy, there
      is an initial sensorial component; however, the neural component is responsible
      for its progressivity.

PMID- 25073541
TI  - Lifestyle factors associated with cognitive functioning in breast cancer
      survivors.
AB  - OBJECTIVE: Weight, physical activity, and sleep are modifiable lifestyle factors
      that impact cognitive functioning in noncancer populations but have yet to be
      examined in cancer survivors. The aim of the study was to assess the relationship
      of obesity, physical activity, and sleep, with cognitive functioning among breast
      cancer survivors. METHODS: Participants were 136 early-stage postmenopausal
      breast cancer survivors who completed an assessment of neuropsychological
      testing, height, weight, physical activity, and sleep. Linear regression models
      examined the associations of the seven neuropsychological domains with obesity,
      physical activity, and sleep. Logistic regression models examined odd of
      impairment in each domain. All models controlled for breast cancer treatment
      variables and relevant demographic and clinical variables. RESULTS: Obese
      participants had significantly worse performance (beta = -5.04, standard error
      (SE) = 2.53) and were almost three times more likely to be impaired (odds ratio
      (OR) = 2.87; 95% CI: 1.02-8.10) on the Information processing domain. The highest
      tertile of physical activity was significantly related to better performance on
      the executive functioning domain (beta = 5.13, SE = 2.42) and attention domain
      (beta = 4.26, SE = 2.07). The middle tertile of physical activity was
      significantly related to better performance (beta = 9.00, SE = 3.09) and
      decreased odds of impairment (OR = 0.89, 95% CI: 0.07-0.91) on the visual-spatial
      domain. More hours of sleep per night was significantly associated with better
      performance (beta = 2.69, SE = 0.98) and decreased odds of impairment (OR = 0.52;
      95% CI: 0.33-0.82) on the verbal functioning domain. CONCLUSIONS: These findings
      suggest that obesity, physical activity, and sleep are related to cognitive
      functioning among breast cancer survivors and have potential to be intervention
      targets to improve cognitive functioning.

PMID- 25073543
TI  - Meta-analysis shows that infants who have suffered neonatal sepsis face an
      increased risk of mortality and severe complications.
AB  - Infants suffering from neonatal sepsis face an increased risk of early death and
      long-term neurodevelopmental delay. This paper analyses and summarises the
      existing data on short-term and long-term outcomes of neonatal sepsis, based on
      12 studies published between January 2000 and 1 April 2012 and covering 3669
      neonates with sepsis. CONCLUSION: Infants who have suffered neonatal sepsis face
      an increased risk of mortality and severe complications such as brain damage and,
      or, neurodevelopmental delay.

PMID- 25073544
TI  - An evaluation of prophylactic treatments to prevent post traumatic joint
      stiffness.
AB  - Arthrofibrosis is a major obstacle to restoring joint function after trauma. The
      objective of this study was to evaluate montelukast, forskolin, and triamcinolone
      as possible means of prophylaxis against the formation of arthrofibrosis. Forty
      eight rats underwent surgical knee trauma with post-operative immobilization in
      full flexion. The treatment groups were: control (CTL), oral montelukast (3.75
      mg/kg/day) (MLK), intra-articular forskolin injections (0.6 mg/kg) (FSK), and
      intra-articular triamcinolone injections (0.68 mg/kg) (STR). Rats were sacrificed
      after 14 days and femorotibial contracture angles were measured with the
      posterior capsule intact and with the posterior capsule cut. A 0.015Nm extension
      moment was applied to the knee. All treatment groups had significant reductions
      in contracture angle compared to the control. Mean contractures with the
      posterior capsule intact were 32 degrees (CTL), 20 degrees  (MLK), 22 degrees 
      (FSK), and 7 degrees  (STR). Contractures with the posterior capsule cut were 28
      degrees  (CTL), 19 degrees  (MLK), 20 degrees  (FSK), and 5 degrees  (STR). The
      STR group was significantly better than FSK and MLK. Triamcinolone injections
      provided dramatic reductions in stiffness. Both forskolin and montelukast
      provided significant, though lesser, reductions in stiffness. While the
      triamcinolone contracture angles were significantly better, the novel treatments
      of forskolin and montelukast provided encouraging results and should be studied
      further.

PMID- 25073545
TI  - Performance of the 2012 Systemic Lupus International Collaborating Clinics and
      the 1997 American College of Rheumatology classification criteria for systemic
      lupus erythematosus in a real-life scenario.
AB  - OBJECTIVE: To evaluate the performance of the 2012 Systemic Lupus International
      Collaborating Clinics (SLICC) criteria in classifying systemic lupus
      erythematosus (SLE) in an uncontrolled real-life scenario. METHODS: Chart review
      study was performed in which each criterion from the 1997 American College of
      Rheumatology (ACR) and the 2012 SLICC criteria to classify SLE was applied to
      patients from an outpatient rheumatology clinic. The clinical diagnosis was used
      as the gold standard. RESULTS: The sensitivity and specificity of the 2012 SLICC
      criteria were 92% and 99%, respectively, compared with the 1997 ACR criteria,
      which were 97% and 99%, respectively. The 2012 SLICC criteria were similar to the
      1997 ACR criteria in terms of positive (98.9% versus 99%) and negative (92.5%
      versus 97.1%) predictive values as well as positive (92 versus 97) and negative
      (0.08 versus 0.03) likelihood ratios. A concordance of 0.96 (95% confidence
      interval [95% CI] 0.92-1.00) was observed between clinical diagnosis and the 1997
      ACR criteria, while the concordance was 0.91 (95% CI 0.85-0.97) for the 2012
      SLICC criteria. Seven SLE patients classified by the 1997 ACR criteria did not
      meet the 2012 SLICC criteria because of either the new definition for lymphopenia
      (2 patients) or the presence of isolated cutaneous involvement (5 patients),
      while 2 SLE patients who were classified by the 2012 SLICC criteria did not meet
      the 1997 ACR criteria because of either the presence of erosive arthritis or
      biopsy-proven nephritis with circulating antinuclear antibodies. CONCLUSION:
      Overall, the 1997 ACR and the 2012 SLICC criteria are similar to classify SLE in
      an uncontrolled real-life scenario, although several new items contained in the
      2012 SLICC criteria could represent a step forward for research purposes in
      selected clinical settings.

PMID- 25073546
TI  - A strategy for characterization of persistent heteroduplex DNA in higher plants.
AB  - Heteroduplex DNA (hDNA) generated during homologous recombination (HR) is an
      important component that shapes genetic diversity in sexually reproducing
      organisms. However, studies of this process in higher plants are limited. This is
      because hDNAs are difficult to capture in higher plants as their reproductive
      developmental model only produces normal gametes and does not preserve the
      mitotic products of the post-meiotic segregation (PMS) process which is crucial
      for studying hDNAs. In this study, using the model system for tree and woody
      perennial plant biology (Populus), we propose a strategy for characterizing hDNAs
      in higher plants. We captured hDNAs by constructing triploid hybrids originating
      from a cross between unreduced 2n eggs (containing hDNA information as a result
      of inhibition chromosome segregation at the PMS stage) with normal male gametes.
      These triploid hybrids allowed us to detect the frequency and location of
      persistent hDNAs resulting from HR at the molecular level. We found that the
      frequency of persistent hDNAs, which ranged from 5.3 to 76.6%, was related to
      locations of the simple sequence repeat markers at the chromosomes, such as the
      locus-centromere distance, the surrounding DNA sequence and epigenetic
      information, and the richness of protein-coding transcripts at these loci. In
      summary, this study provides a method for characterizing persistent hDNAs in
      higher plants. When high-throughput sequencing techniques can be incorporated,
      genome-wide persistent hDNA assays for higher plants can be easily carried out
      using the strategy presented in this study. 

PMID- 25073547
TI  - Effects of water temperature on mortality in Megalocytivirus-infected rock bream
      Oplegnathus fasciatus (Temminck et Schlegel) and development of protective
      immunity.
AB  - Rock bream iridovirus (RBIV) causes huge losses, especially in rock bream
      Oplegnathus fasciatus. Rock bream injected with RBIV and held at 29, 26, 23 or 20
      degrees C had 100% mortality. Conversely, all infected fish held at 17  degrees
      C survived even after the temperature was progressively increased to 26  degrees
      C at 100 dpi. Rock bream exposed to virus and held for 2, 4 and 7 days at 23/26 
      degrees C before the temperature was reduced to 17  degrees C had mortality rates
      of 26.6/73.2%, 66.6/100% and 93.4/100%, respectively, through 100 dpi. When
      surviving fish had the water temperature increased from 17 to 26  degrees C at
      100 dpi, they did not exhibit signs of disease and had low virus copy numbers
      (below 10(3)). To investigate the development of a protective immune, rock bream
      were infected with RBIV and held at 23  degrees C before shifting the water
      temperature to 17  degrees C at 4 dpi. All injected fish survived until 120 dpi.
      While 100% of the previously unexposed fish died, 80.2% of the previously
      infected fish survived. When the survivors were rechallenged again at 160 dpi, no
      further mortality occurred. The high survival rate of fish following rechallenge
      with RBIV indicates that protective immunity was established in the surviving
      rock bream.

PMID- 25073548
TI  - Evaluation of the length of competitive life in Hungarian sport horses.
AB  - The aim of this study was to analyse the duration of the competitive life of
      jumping horses in Hungary to assess the potential for genetic evaluation and to
      get information about the risk factors affecting jumping performance of sport
      horses. The data set included lifetime performance in jumping competitions for
      8475 horses born from 1992 onwards with records between 1996 and 2011 (32.7% were
      right-censored). Longevity was measured as the number of years spent in the
      competition. Discrete time survival model included fixed effects of gender, age
      at first competition, and the time-dependent effect of competition level. All
      fixed effects were highly significant (p < 0.001). The highest risk of ending the
      race career was estimated for horses competing in the lowest level (category 1)
      events. The smallest risk was found in horses competing in the highest category.
      The culling risk for stallions was 15% higher, for geldings 20% lower when
      compared to mares. As the age at the first competition result increased, the risk
      ratio also increased. Risk ratios of horses starting as 8 years old or older were
      56% higher than those of 5-year-old horses. The longest time in sport tracks
      belonged to horses starting their career as 4 years old. Their culling risk was
      20% lower than those of 5-year-old horses. The heritability of the length of
      competitive life was 0.17. Breeding values were predicted for each animals, and
      47 showed an accuracy greater than 0.60. The clear benefit of the analysis was
      shown by comparison of offspring to extreme stallion groups.

PMID- 25073549
TI  - Vaccine Potential of Two Previously Uncharacterized African Swine Fever Virus
      Isolates from Southern Africa and Heterologous Cross Protection of an Avirulent
      European Isolate.
AB  - African swine fever (ASF) is a mostly fatal viral infection of domestic pigs for
      which there is no vaccine available. The disease is endemic to most of sub
      Saharan Africa, causes severe losses and threatens food security in large parts
      of the continent. Naturally occurring attenuated ASF viruses have been tested as
      vaccine candidates, but protection was variable depending on the challenge virus.
      In this study, the virulence of two African isolates, one from a tick vector and
      the other from an indigenous pig, was determined in domestic pigs to identify a
      potential vaccine strain for southern Africa. Neither isolate was suitable as the
      tick isolate was moderately virulent and the indigenous pig virus was highly
      virulent. The latter was subsequently used as heterologous challenge in pigs
      first vaccinated with a naturally attenuated isolate previously isolated in
      Portugal. Although a statistically significant reduction in death rate and virus
      load was observed compared with unvaccinated pigs post-challenge, all pigs
      succumbed to infection and died. 

PMID- 25073550
TI  - Environmental factors in benign migratory glossitis and psoriasis: retrospective
      study of the association of emotional stress and alcohol and tobacco consumption
      with benign migratory glossitis and cutaneous psoriasis.
AB  - BACKGROUND: The association between benign migratory glossitis (BMG) and
      psoriasis (PS) has been reported in the literature. OBJECTIVE: This study aimed
      to determinate the environmental factors related to BMG and PS and to investigate
      their interactions. METHODS: The study population included 129 patients with PS,
      399 patients with BMG and a control group (CG) of 5472 individuals with neither
      PS nor BMG. The environmental factors evaluated in this study included alcohol
      and tobacco consumption and emotional stress. The Pearson's chi-squared test was
      used for analysing the association of the environmental factors with PS and BMG.
      RESULTS: The prevalence of alcohol consumption in the PS group was significantly
      higher than that in the CG. Tobacco consumption had a weak negative association
      with the BMG group. With respect to the PS group, no statistically significant
      association was observed. Emotional stress was the most important factor in the
      two study groups. Emotional stress and alcohol use together presented a higher
      incidence in the study groups than in the CG. Emotional stress and tobacco
      consumption together had a three times higher incidence in the PS group than in
      the BMG group. The association of emotional stress, alcohol and tobacco
      consumption in the PS group was four times higher than that in the CG.
      LIMITATIONS: This study was limited by the lack of the information about
      frequency, type and length time of use of tobacco and alcohol, and by difficult
      to measure stress thought self-report questionnaire. CONCLUSION: The interactions
      between PS and environmental factors differ from those between BMG and
      environmental factors. These differences among interactions may be responsible
      for different forms of manifestations of these diseases, considering being both
      the same disease.

PMID- 25073552
TI  - [Cutaneous T-cell lymphomas: still a therapeutic challenge].

PMID- 25073551
TI  - Simulation with cells in vitro of tamoxifen treatment in premenopausal breast
      cancer patients with different CYP2D6 genotypes.
AB  - BACKGROUND AND PURPOSE: Tamoxifen is a prodrug that is metabolically activated by
      4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via
      another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active
      secondary metabolite endoxifen through a cytochrome P450 2D6 variant system
      (CYP2D6). To elucidate the mechanism of action of tamoxifen and the importance of
      endoxifen for its effect, we determined the anti-oestrogenic efficacy of
      tamoxifen and its metabolites, including endoxifen, at concentrations
      corresponding to serum levels measured in breast cancer patients with various
      CYP2D6 genotypes (simulating tamoxifen treatment). EXPERIMENTAL APPROACH: The
      biological effects of tamoxifen and its metabolites on cell growth and oestrogen
      responsive gene modulation were evaluated in a panel of oestrogen receptor
      positive breast cancer cell lines. Actual clinical levels of tamoxifen
      metabolites in breast cancer patients were used in vitro along with actual levels
      of oestrogens observed in premenopausal patients taking tamoxifen. KEY RESULTS:
      Tamoxifen and its primary metabolites (4OHT and NDMTAM) only partially inhibited
      the stimulant effects of oestrogen on cells. The addition of endoxifen at
      concentrations corresponding to different CYP2D6 genotypes was found to enhance
      the anti-oestrogenic effect of tamoxifen and its metabolites with an efficacy
      that correlated with the concentration of endoxifen; at concentrations
      corresponding to the extensive metabolizer genotype it further inhibited the
      actions of oestrogen. In contrast, lower concentrations of endoxifen
      (intermediate and poor metabolizers) had little or no anti-oestrogenic effects.
      CONCLUSIONS AND IMPLICATIONS: Endoxifen may be a clinically relevant metabolite
      in premenopausal patients as it provides additional anti-oestrogenic actions
      during tamoxifen treatment.

PMID- 25073555
TI  - Vascular niches: endothelial cells as tissue- and site-specific multifunctional
      team players in health and disease.
AB  - The cardiovascular system is a circulatory system that transports the blood and
      reaches out to almost every site of the body. Endothelial cells (EC) as the
      innermost cell layer of blood vessels constitute a huge interface between the
      blood and nearly all other tissues and cells. Although blood vessels and their EC
      were considered as rather inert and passive conduits early in the history of
      vascular discoveries, progress in vascular research now suggests that EC are
      actively involved in a plethora of physiological or pathophysiological processes.
      Endothelial heterogeneity and the concept of vascular niches are in the spotlight
      of current research in vascular biology. Endothelial heterogeneity comprises
      morphologic, molecular and functional features. It allows EC to adapt to the
      organ- and site-specific requirements exhibited by different segments of the
      vascular tree. In organ-specific vascular niches, EC mutually interact with
      neighboring cells. EC-derived cytokines, called angiokines, acting in a paracrine
      (angiocrine) fashion have been shown to be decisively involved in various
      biological processes ranging from stem cell maintenance to organ regeneration as
      well as cancer progression and metastasis. In summary, EC should always be
      considered as teammates in the maintenance and regulation of complex
      multicellular network interactions in health and disease. 

PMID- 25073561
TI  - Malaria diagnostic capacity in health facilities in Ethiopia.
AB  - BACKGROUND: Accurate early diagnosis and prompt treatment is one of the key
      strategies to control and prevent malaria in Ethiopia where both Plasmodium
      falciparum and Plasmodium vivax are sympatric and require different treatment
      regimens. Microscopy is the standard for malaria diagnosis at the health centres
      and hospitals whereas rapid diagnostic tests are used at community-level health
      posts. The current study was designed to assess malaria microscopy capacity of
      health facilities in Oromia Regional State and Dire Dawa Administrative City,
      Ethiopia. METHODS: A descriptive cross-sectional study was conducted from
      February to April 2011 in 122 health facilities, where health professionals were
      interviewed using a pre-tested, standardized assessment tool and facilities'
      laboratory practices were assessed by direct observation. RESULTS: Of the 122
      assessed facilities, 104 (85%) were health centres and 18 (15%) were hospitals.
      Out of 94 health facilities reportedly performing blood films, only 34 (36%) used
      both thin and thick smears for malaria diagnosis. The quality of stained slides
      was graded in 66 health facilities as excellent, good and poor quality in
      11(17%), 31 (47%) and 24 (36%) respectively. Quality assurance guidelines and
      malaria microscopy standard operating procedures were found in only 13 (11%)
      facilities and 12 (10%) had involved in external quality assessment activities,
      and 32 (26%) had supportive supervision within six months of the survey. Only
      seven (6%) facilities reported at least one staff's participation in malaria
      microscopy refresher training during the previous 12 months. Although most
      facilities, 96 (79%), had binocular microscopes, only eight (7%) had the
      necessary reagents and supplies to perform malaria microscopy. Treatment
      guidelines for malaria were available in only 38 (31%) of the surveyed
      facilities. Febrile patients with negative malaria laboratory test results were
      managed with artemether-lumefantrine or chloroquine in 51% (53/104) of assessed
      health facilities. CONCLUSIONS: The current study indicated that most of the
      health facilities had basic infrastructure and equipment to perform malaria
      laboratory diagnosis but with significant gaps in continuous laboratory supplies
      and reagents, and lack of training and supportive supervision. Overcoming these
      gaps will be critical to ensure that malaria laboratory diagnosis is of high
      quality for better patient management.

PMID- 25073562
TI  - In situ polymerization deposition of porous conducting polymer on reduced
      graphene oxide for gas sensor.
AB  - Porous conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) nanocomposite
      prepared on reduced graphene oxide (RGO) film was used as efficient chemiresistor
      sensor platform for NO2 detection. The comparable electrical performance between
      RGO and porous PEDOT nanostructure, the large surface area and opening porous
      structure of this RGO/porous PEDOT nanocomposite resulted in excellent
      synergistic effect. The gas sensing performance revealed that, in contrast to
      bare RGO, the RGO/porous PEDOT exhibited the enhanced sensitivity (2 orders of
      magnitude) as well as response and recovery performance. As a result of the
      highly uniform distribution of PEDOT porous network and excellent synergetic
      effect between RGO and porous PEDOT, this nanocomposite based sensor exhibited
      higher selectivity to NO2 in contrast to other oxidant analyte gases, e.g., HCl,
      H2S and SO2. 

PMID- 25073563
TI  - Deaths attributed to heat, cold, and other weather events in the United States,
      2006-2010.
AB  - OBJECTIVES: This report examines heat-related mortality, cold-related mortality,
      and other weather-related mortality during 2006-2010 among subgroups of U.S.
      residents. METHODS: Weather-related death rates for demographic and area-based
      subgroups were computed using death certificate information. Adjusted odds ratios
      for weather-related deaths among subgroups were estimated using logistic
      regression. RESULTS AND CONCLUSIONS: During 2006-2010, about 2,000 U.S. residents
      died each year from weather-related causes of death. About 31% of these deaths
      were attributed to exposure to excessive natural heat, heat stroke, sun stroke,
      or all; 63% were attributed to exposure to excessive natural cold, hypothermia,
      or both; and the remaining 6% were attributed to floods, storms, or lightning.
      Weather-related death rates varied by age, race and ethnicity, sex, and
      characteristics of decedent's county of residence (median income, region, and
      urbanization level). Adjustment for region and urbanization decreased the risk of
      heat-related mortality among Hispanic persons and increased the risk of cold
      related mortality among non-Hispanic black persons, compared with non-Hispanic
      white persons. Adjustment also increased the risk of heat-related mortality and
      attenuated the risk of cold-related mortality for counties in the lower three
      income quartiles. The differentials in weather-related mortality observed among
      demographic subgroups during 2006-2010 in the United States were consistent with
      those observed in previous national studies. This study demonstrated that a
      better understanding of subpopulations at risk from weather-related mortality can
      be obtained by considering area-based variables (county median household income,
      region, and urbanization level) when examining weather-related mortality
      patterns.

PMID- 25073564
TI  - Usefulness of growth differentiation factor-15 levels to predict diabetic
      cardiomyopathy in asymptomatic patients with type 2 diabetes mellitus.
AB  - Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that
      increased in patients with established type 2 diabetes mellitus (DM). Diabetic
      cardiomyopathy (DC), defined as left ventricular diastolic dysfunction (LVDD) in
      patients with type 2 DM in the absence of arterial hypertension, heart disease,
      or other heart disease, was assessed by GDF-15 levels in type 2 DM patients with
      and without DC. A total of 213 DM outpatients had blood samples drawn and on the
      same day (basal) underwent echocardiography and treadmill exercise testing.
      Plasma GDF-15 concentrations were measured by an enzyme-linked immunosorbent
      assay (ELISA) at baseline. DC was diagnosed in the presence of LVDD, defined when
      early mitral valve flow velocity (E) and early diastolic lengthening velocity
      (E') ratio was E/E' >= 15. The prevalence of DC was 21.13%. GDF-15 levels were
      higher in patients with DC compared with those without DC (5,273 [8,708.4] vs
      2,812.66 [7,662.1] pg/ml, respectively, p <0.001). We assessed predictors of DC
      using multivariate regression analysis. GDF-15 (odds ratio 9.9; 95% confidence
      interval [3.9 to 24.5], p <0.001) was the unique independent predictor of DC. The
      results of receiver operating characteristic curve show that the cut-off point of
      3,812 pg/ml of GDF-15 was indicative for DC (AUC = 0.83, sensitivity = 82.2% and
      specificity = 70.2%, p <0.0001). In conclusion, GDF-15 represents a useful and
      novel tool to screen DC in patients with type 2 DM.

PMID- 25073565
TI  - Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias
      and outcomes in Fabry disease.
AB  - The aim of this study was to investigate the impact of myocardial fibrosis in
      Fabry disease. Seventy-three patients with genetically confirmed Fabry disease
      were followed for 4.8 +/- 2.4 years. In accordance with current guidelines, 57
      patients received enzyme replacement therapy (ERT) after study inclusion, whereas
      16 did not. At baseline and latest possible follow-up, myocardial fibrosis was
      assessed noninvasively by cardiac magnetic resonance, and biomarkers of collagen
      metabolism were determined. Holter electrocardiography and clinical follow-up at
      yearly intervals were used to monitor malignant ventricular arrhythmias (MVAs;
      nonsustained and sustained ventricular tachycardia and sudden cardiac death). In
      total, 48 patients (66%) showed fibrosis assessed by late enhancement (LE) at
      baseline, and 4 patients developed new LE during follow-up, 2 of them despite
      ERT. The 2 patients receiving ERT (1.4 +/- 1.9% vs 2.5 +/- 2.6%, p <0.001) and
      the patients not receiving ERT (0.5 +/- 0.8% vs 0.7 +/- 1.0%, p = 0.035) showed a
      progression of LE during follow-up. None of the patients displayed reductions of
      LE during follow-up. Collagen biomarkers were elevated in patients with and
      without LE but did not correlate with LE amount. Thirteen LE-positive patients at
      the baseline examination had documented MVAs (including 5 sudden cardiac deaths),
      whereas none of the patients without LE had MVAs. The yearly increase in fibrosis
      was 0.9 +/- 0.6% in patients with MVAs and 0.2 +/- 0.3% in patients without MVAs
      (p <0.001). Logistic multivariate regression analysis revealed that the annual
      increase in fibrosis during follow-up was the only independent predictor of MVAs.
      In conclusion, myocardial fibrosis in Fabry disease is progressive, apparently
      not modified by ERT, and a crucial outcome determinant.

PMID- 25073567
TI  - Usefulness of N-terminal pro-brain natriuretic peptide levels to predict success
      of weaning from intra-aortic balloon pumping.
AB  - There is currently no reliable method of predicting the success of weaning from
      intra-aortic balloon pumping (IABP). The aim of this study was to investigate the
      ability of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level to
      predict the success of weaning from IABP. Consecutive patients scheduled for
      weaning from IABP were prospectively enrolled. NT-proBNP levels were measured at
      baseline (before the start of weaning) and cessation (just before cessation of
      IABP). Changes in NT-proBNP level between baseline and cessation were analyzed in
      2 groups of patients: those who were successfully weaned and those who were not
      successfully weaned for any reason, including a decision to discontinue weaning,
      worsening of pulmonary edema after cessation of IABP, or unstable hemodynamics
      after cessation of IABP. A total of 30 patients were enrolled (mean age 66 +/- 12
      years, 16 men, 16 with acute myocardial infarctions, and 14 with acute
      exacerbation of chronic heart failure). Median (interquartile range) baseline NT
      proBNP levels were not significantly different between the successful and
      unsuccessful weaning groups (4,200 [1,400 to 8,752] pg/ml vs (5,620 [2,035 to
      13,950] pg/ml, p = 0.30). In the unsuccessful weaning group, the median NT-proBNP
      level was significantly higher at cessation (9,995 [2,920 to 15,100] pg/ml) than
      at baseline (p = 0.008). All patients with decreases in NT-proBNP level between
      baseline and cessation were successfully weaned from IABP. In conclusion, these
      results show that NT-proBNP levels were useful for predicting the success of
      weaning from IABP. If the NT-proBNP level increases during weaning from IABP,
      more intense management should be considered.

PMID- 25073566
TI  - Plasma-free fatty acids, fatty acid-binding protein 4, and mortality in older
      adults (from the Cardiovascular Health Study).
AB  - Plasma-free fatty acids (FFAs) are largely derived from adipose tissue. Elevated
      levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic
      chaperone of fatty acids, have been associated with adverse cardiovascular
      outcomes, but limited data are available on the relation of these biomarkers with
      cardiovascular and total mortality. We studied 4,707 participants with a mean age
      of 75 years who had plasma FFA and FABP4 measured in 1992 to 1993 as part of the
      Cardiovascular Health Study, an observational cohort of community-dwelling older
      adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox
      proportional hazard regression was used to determine the association between FFA,
      FABP4, and mortality. In fully adjusted models, FFA were associated with dose
      dependent significantly higher total mortality (hazard ratio [HR] per SD: 1.14,
      95% confidence interval [CI] 1.09 to 1.18), but FABP4 levels were not (HR 1.04,
      95% CI 0.98 to 1.09). In a cause-specific mortality analysis, higher
      concentrations of FFA were associated with significantly higher risk of death
      because of cardiovascular disease, dementia, infection, and respiratory causes
      but not cancer or trauma. We did not find evidence of an interaction between FFA
      and FABP4 (p = 0.45), but FABP4 appeared to be associated with total mortality
      differentially in men and women (HR 1.17, 95% CI 1.08 to 1.26 for men; HR 1.02,
      95% CI 0.96 to 1.07 for women, interaction p value <0.001). In conclusion, in a
      cohort of community-dwelling older subjects, elevated plasma concentrations of
      FFA, but not FABP4, were associated with cardiovascular and noncardiovascular
      mortality.

PMID- 25073569
TI  - Chitosan as an adjuvant-like substrate for dendritic cell culture to enhance
      antitumor effects.
AB  - To induce monocyte differentiation into dendritic cells (DCs) is the essential
      protocol for the DC-mediated cancer immunotherapy. In this study, monocytes
      isolated from mouse bone marrow were cultured on chitosan substrate to evaluate
      the effect of the chitosan culture system on the induction and tumor protection
      of DCs. Compared to tissue culture polystyrene (TCPS), the chitosan culture
      system could enhance monocyte aggregation and detachment with increased MTT
      reduction activity and expression of DC marker CD11c and LPS co-receptor CD14.
      Moreover, compared to TCPS, chitosan could enhance lipopolysaccharides (LPS)
      stimulated DCs to secrete higher amount of IL-12. More importantly, vaccination
      of tumor lysate-pulsed DCs harvested from chitosan could increase cytotoxic T
      lymphocyte (CTL) activity and showed significantly enhanced anti-tumor effect
      than those from TCPS. Therefore, the current study demonstrated that a protocol
      to culture DCs on a less-adherent chitosan substrate followed by treatment with
      tumor lysate has the potential in future DC-based vaccine application. 

PMID- 25073568
TI  - Comparison of risk of acute kidney injury after primary percutaneous coronary
      interventions with the transradial approach versus the transfemoral approach
      (from the PRIPITENA urban registry).
AB  - The risk of acute kidney injury (AKI) is a major issue after percutaneous
      coronary interventions (PCIs), especially in the setting of ST-elevation
      myocardial infarction. Preliminary data from large retrospective registries seem
      to show a reduction of AKI when a transradial (TR) approach for PCI is adopted.
      Little is known about the relation between vascular access and AKI after emergent
      PCI. We here report the results of the Primary PCI from Tevere to Navigli
      (PRIPITENA), a retrospective database of primary PCI performed at high-volume
      centers in the urban areas of Rome and Milan. Primary end point of this study was
      the occurrence of AKI in the TR and transfemoral (TF) access site groups.
      Secondary end points were major adverse cardiovascular events, stent thrombosis,
      and Thrombolysis in Myocardial Infarction major and minor bleedings. The database
      included 1,330 patients, 836 treated with a TR and 494 with a TF approach. After
      a propensity-matched analysis performed to exclude possible confounders, we
      identified 450 matched patients (225 TR and 225 TF). The incidence of AKI in the
      2 matched groups was lower in patients treated with TR primary PCI (8.4% vs
      16.9%, p = 0.007). Major adverse cardiovascular events and stent thrombosis were
      not different among study groups, whereas major bleedings were more often seen in
      the TF group. At multivariate analysis, femoral access was an independent
      predictor of AKI (odds ratio 1.654, 95% confidence interval 1.084 to 2.524, p =
      0.042). In conclusion, in this database of primary PCI, the risk of AKI was lower
      with a TR approach, and the TF approach was an independent predictor for the
      occurrence of this complication.

PMID- 25073570
TI  - The effects of cystatin C and alkaline phosphatase changes on cognitive function
      12-months after bariatric surgery.
AB  - BACKGROUND: The mechanisms for improved cognitive function post-bariatric surgery
      are not well understood. Markers of kidney and liver function (i.e., cystatin C
      and alkaline phosphatase (ALP)) are elevated in obese individuals and associated
      with poor neurocognitive outcomes in other samples. Bariatric surgery can improve
      cystatin C and ALP levels, but no study has examined whether such changes
      correspond to post-operative cognitive benefits. METHODS: 78 bariatric surgery
      patients completed a computerized cognitive test battery prior to and 12-months
      after surgery. All participants underwent an eight-hour fasting blood draw to
      quantify cystatin C and ALP concentrations. RESULTS: Cognitive function improved
      after surgery. Cystatin C levels decreased at the 12-month follow-up; however, no
      changes were found in ALP concentrations. At baseline, higher cystatin C levels
      predicted worse attention/executive function, but no such effects emerged for
      ALP. Regression analyses controlling for possible medical and demographic
      confounds and baseline factors revealed that decreased ALP levels following
      surgery predicted better attention/executive function and memory abilities. Post
      surgery changes in cystatin C did not correspond to cognitive improvements.
      CONCLUSIONS: Decreased ALP levels predicted better cognition following bariatric
      surgery, suggesting improved liver function as a possible mechanism of post
      operative cognitive benefits. Future studies with neuroimaging and longer follow
      up periods are needed to determine whether bariatric surgery can decrease risk
      for adverse brain changes and dementia in severely obese persons via improved
      metabolic function.

PMID- 25073571
TI  - Novel characterization of gait impairments in people with multiple sclerosis by
      means of the gait profile score.
AB  - The assessment of gait abnormalities in individuals with multiple sclerosis (MS)
      represents a key factor in evaluating the effectiveness of rehabilitation
      treatments. Despite the availability of sophisticated equipment to objectively
      evaluate the kinematic aspects of gait, there are still some difficulties in
      processing the large and complex amount of data they produce in the daily
      clinical routine. On the basis of the above-mentioned considerations we propose a
      novel characterization of gait kinematics in individuals with MS, based on a
      single measure (gait profile score, GPS) obtained from a quantitative three
      dimensional analysis of gait performed using an opto-electronic system. We also
      investigated the correlation between GPS and the Expanded Disability Status Scale
      (EDSS) values. Thirty-four patients suffering from relapsing-remitting MS (13
      female, 21 male, mean age 46.7 years) with an EDSS score of <=6 underwent a gait
      analysis from which the GPS index was calculated. Their results were compared
      with those of a control group of healthy age- and gender-matched subjects. The
      GPS of individuals with MS was found significantly higher with respect to
      controls (9.12 degrees  vs. 5.67 degrees , p<0.001) as the result of kinematic
      differences in gait patterns referring to pelvic tilt and rotation, hip flexion
      extension and rotation, knee flexion-extension and ankle dorsi- and plantar
      flexion. A moderate correlation was also found between the EDSS score of the
      participants and their GPS values (r = 0.63, p < 0.001). The GPS index thus
      appears suitable to represent gait deviations from physiological patterns in
      individuals affected by MS and potentially useful in assessing the outcomes
      related both to rehabilitation programs and pharmacologic/physical therapies.

PMID- 25073572
TI  - ALS-Plus - where does it begin, where does it end?

PMID- 25073574
TI  - Therapeutic potential of metabotropic glutamate receptor 4-positive allosteric
      modulator TAS-4 in rodent models of movement disorders.
AB  - Parkinson's disease (PD) is a very serious neurological disorder, and current
      methods of treatment fail to achieve long-term control. Previous studies suggest
      that stimulation of the metabotropic glutamate receptor 4 (mGluR4) represents a
      promising new approach to the symptomatic treatment of Parkinson's disease (PD).
      Preclinical models using both agonists and positive allosteric modulators of
      mGluR4 have demonstrated the potential for this receptor for the treatment of PD.
      In the present study, we describe the pharmacological characterization of an
      mGluR4 PAM, N-(2, 4-dichlorophenyl) pyridine-2-carboxamide (TAS-4), in several
      rodent PD models. TAS-4 is a potent and selective mGluR4 PAM of the human mGluR4
      receptor (EC50- 287.8nM). TAS-4 showed efficacy alone or when administered in
      combination with l-DOPA. When administered alone, TAS-4 exhibited efficacy in
      reversing haloperidol-induced catalepsy. In addition, acute TAS-4 dose
      dependently potentiated contralateral turning behavior induced by a threshold
      dose of l-3,4-dihydroxyphenylalanine (l-DOPA, 4mg/kg i.p.), a classical test for
      antiparkinson drug screening. Subchronic (28days, twice a day) TAS-4 (10mg/kg
      i.p.)+l-DOPA (4mg/kg i.p.) did not induce sensitization to turning behavior or
      abnormal involuntary movements during the course of treatment. Moreover,
      subchronic administration of a fully effective dose of l-DOPA (8mg/kg i.p.)
      significantly induces sensitization to turning behavior or abnormal involuntary
      movements. Results showed that TAS-4, in association with a low dose of l-DOPA,
      displayed antiparkinsonian activity similar to that produced by a full dose of l
      DOPA without exacerbating abnormal motor side effects.

PMID- 25073573
TI  - Nerve safety of tanezumab, a nerve growth factor inhibitor for pain treatment.
AB  - OBJECTIVE: To evaluate peripheral nerve safety and clinical efficacy of tanezumab
      in patients with painful osteoarthritis. METHODS: Patients received intravenous
      tanezumab 5mg, tanezumab 10mg, or placebo every 8 weeks for 24 weeks.
      Neurological safety was evaluated via a composite score (nerve conduction
      attributes and heart rate variability with deep breathing; Sigma5NC + HRdb),
      intraepidermal nerve fiber (IENF) density, and clinical assessments. Efficacy and
      general safety were also evaluated. RESULTS: The study was stopped prematurely by
      an FDA partial clinical hold (joint safety issues in other studies). Differences
      in change from baseline to Week 24 in Sigma5NC + HRdb were not significant.
      Tanezumab 5mg vs placebo exceeded the prespecified clinically important
      difference using last observation carried forward imputation, but not with
      observed data or when patients with evidence of neuropathy at baseline were
      excluded. No significant differences were found in individual nerve conduction
      measures. No treatment exceeded the prespecified clinically important decrease in
      IENF. Tanezumab resulted in significant improvement in pain, physical function,
      and Patient's Global Assessment. Safety was similar to previous tanezumab
      clinical trials. CONCLUSIONS: Tanezumab has a modulating effect on pain, does not
      appear to increase neurological safety signals, and offers a potentially
      promising, novel approach in treatment of pain.

PMID- 25073575
TI  - Cocaine-induced environmental conditioning: sleep deprivation as a neglected
      contributor.

PMID- 25073576
TI  - Serum VEGF and bFGF in patients with inflammatory bowel diseases.
AB  - AIM: The role of angiogenesis in inflammatory bowel diseases (IBD) remains
      controversial. We investigated the role of serum concentration levels of VEGF and
      bFGF in IBD patients and assessed their potential association to disease
      activity. PATIENTS AND METHODS: Blood samples were obtained from 40 IBD patients
      with moderate to severe attack of the disease and 40 healthy controls. VEGF and
      bFGF serum levels were assessed. C-reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR) were measured as markers of disease activity and
      correlated to VEGF and bFGF. RESULTS: The demographic characteristics of both
      patients and controls were homogenous, in regard of age, sex, smoke and
      concomitant diseases. VEGF serum levels were significantly higher in IBD patients
      compared to controls (1158.5+/-845.4 pg/ml vs 464.6+/-283.1 pg/ml, p<0.001).
      Serum concentration levels of bFGF did not differ between groups. Linear
      regression analysis showed no direct association between VEGF or bFGF and CRP or
      ESR. CONCLUSION: VEGF, but not bFGF, may have a prominent role in patients with
      IBD, without though direct association to disease activity. KEY WORDS: bFGF,
      Inflammatory bowel disease, VEGF.

PMID- 25073577
TI  - Multidisciplinary care improves amputation-free survival in patients with chronic
      critical limb ischemia.
AB  - BACKGROUND: This study was conducted to quantify the effect of multidisciplinary
      care (MDC) on amputation-free survival (AFS) and wound healing within a chronic
      critical limb ischemia (CLI) population. METHODS: We performed a retrospective,
      single-center cohort study of consecutive CLI patients presenting to the Vascular
      Surgery Service. Patients who received initial and follow-up wound care from the
      MDC were compared with patients who received standard wound care (SWC). The MDC
      team consisted of vascular, plastic, and podiatric surgeons who jointly managed
      wound care and directed any other consults or services as deemed necessary. SWC
      consisted of an inconsistent mix of providers without a defined manager,
      including nurses, wound care midlevel providers, general surgeons, internists, or
      the patients themselves. The referring physician determined the allocation of
      patients. The primary outcome variable was AFS, with a secondary evaluation of
      wound healing. The effects of baseline demographics, comorbid medical conditions,
      laboratory values, ischemic lesion severity and location, Rutherford
      classification, and participation in MDC were assessed. Significant univariate
      predictors (P < .10) of AFS were entered into a multivariate Cox regression model
      and assessed at an alpha = .05. RESULTS: Between August 2010 and June 2012, 146
      CLI patients (91 male [63%]) were evaluated by the Vascular Surgery Service and
      were followed up for a median of 539 days (interquartile range 314-679 days).
      Ischemic tissue loss was present in 85 patients (38 at Rutherford category 5, and
      47 at Rutherford category 6). Within this cohort, 51 (60%) had MDC, and 34 (40%)
      had SWC. Fifty-eight patients (68%) underwent revascularization (open in 17,
      endovascular in 35, and hybrid in 6), 14 (8%) were managed with primary major
      amputation, and 13 (15%) declined revascularization. AFS was superior for
      patients in the MDC arm vs the SWC arm (593.3 +/- 53.5 days vs 281.0 +/- 38.2
      days; log-rank, P = .02). Wound-healing times favored the MDC arm over the SWC
      arm (444.5 +/- 33.2 days vs 625.2 +/- 126.5 days), although this was not
      statistically significant (log-rank, P = .74). Multivariate modelling revealed
      that independent predictors of major amputation or death, or both, were
      nonrevascularized patients (hazard ratio [HR], 3.76; 95% confidence interval
      [CI], 1.78-8.02; chi(2), P < .01), treatment by SWC (HR, 2.664; 95% CI, 1.23
      5.77; chi(2), P = .012), and baseline nonambulatory status (HR, 1.89; 95% CI,
      1.17-2.85; chi(2), P < .01). CONCLUSIONS: MDC pathways for the management of a
      population of CLI patients improved AFS by greater than twofold and should be the
      standard of care for the CLI population. Baseline nonambulatory status and
      unrevascularized patients also predict worse AFS. Wound healing remains prolonged
      regardless of preoperative or postoperative wound care. Future study is required
      to evaluate the costs and functional outcomes for MDC in the management of CLI.

PMID- 25073579
TI  - Reply to "Response to 'Interleukin-6 signal transduction and its role in hepatic
      lipid metabolic disorders' by Hassan et al.".

PMID- 25073578
TI  - IL-35 promotes pancreas cancer growth through enhancement of proliferation and
      inhibition of apoptosis: evidence for a role as an autocrine growth factor.
AB  - Interleukin-35 (IL-35), an IL-12 cytokine family member, mediates the immune
      inhibitory function of regulatory T cells (Treg). We assayed the presence of IL
      35 in paraffin-embedded human pancreas cancer (PCAN) and unexpectedly found IL-35
      was expressed mainly by epithelial derived PCAN cells, but not by Treg. We
      further examined the expression and effect of exogenous IL-35 in human PCAN cell
      lines and found IL-35 promoted growth and inhibited apoptosis in PCAN cell lines.
      IL-35 induced proliferation correlated with an increase in cyclin B, cyclin D,
      cdk2, and cdk4 and a decrease in p27 expression, while inhibition of apoptosis
      was associated with an increase in Bcl-2 and a decrease in TRAILR1. We conclude
      IL-35 is produced by PCAN in vivo and promotes PCAN cell line growth in vitro.
      These results might indicate an important new role for IL-35 as an autocrine
      growth factor in PCAN growth. 

PMID- 25073580
TI  - Women's use of complementary and alternative medicine in pregnancy: A search for
      holistic wellbeing.
AB  - BACKGROUND: A number of studies have found increased use of complementary and
      alternative medicine (CAM) during pregnancy and birth. However, little is known
      about women's motivation in seeking CAM during pregnancy or their experiences of
      use in relation to their pregnancy and childbirth journey. METHODS: A narrative
      study sought to explore the meaning and significance of CAM use in pregnancy from
      the perspective of CAM users. Narrative style interviews were conducted with 14
      women who had used a range of CAMs during pregnancy and birth. Data analysis
      focussed on the meaning and significance of CAM use in pregnancy and a number of
      core themes emerged. FINDINGS: This paper focusses on the theme which illustrates
      the meaning behind women's use of CAM in pregnancy and childbirth as one of
      seeking holistic wellbeing. CONCLUSION: Participants engaged with CAM as a way of
      fulfilling their physical, emotional and spiritual needs during pregnancy. Use of
      CAM signified women's desire to be proactive in health seeking behaviours.

PMID- 25073582
TI  - Improvement in stress urinary incontinence after abdominoplasty.
AB  - BACKGROUND: Abdominoplasty is indicated in cosmetic surgery to improve body
      contour. Results from several studies suggest that abdominoplasty also could be
      therapeutic for certain individuals with urinary incontinence. OBJECTIVES: The
      authors sought to determine the potential therapeutic effect of abdominoplasty on
      urinary incontinence in a large population to confirm the findings of smaller
      studies and to identify common characteristics of patients who experience the
      greatest improvement in these symptoms postoperatively. METHODS: Through a
      retrospective chart review, the authors identified 250 patients who underwent
      cosmetic abdominoplasty. These patients were invited to participate in a survey
      to ascertain changes in stress urinary incontinence (SUI) symptoms after
      abdominoplasty. Patients were subgrouped according to postoperative changes in
      their urinary incontinence symptoms, and the subgroups were evaluated for common
      within-group characteristics. RESULTS: Of the 250 patients who underwent
      abdominoplasty during the period of interest, 100 (40%) completed the survey,
      half of whom (n=50) reported incontinence preoperatively. After abdominoplasty,
      30 (60%) of these 50 patients noted improvement in their symptoms, and the other
      20 (40%) reported no improvement. Lack of previous cesarean section was a
      predictor of improvement in SUI symptoms after abdominoplasty. CONCLUSIONS:
      Abdominoplasty to improve body contour also may alleviate symptoms of SUI,
      especially among patients who have not undergone previous cesarean section. LEVEL
      OF EVIDENCE: 4.

PMID- 25073583
TI  - Parent-mediated intervention: adherence and adverse effects.
AB  - PURPOSE: The purpose of this study was to investigate parent implementation of
      home-based therapy regimens, and the relationship between implementation and
      family-level outcomes. METHOD: A stratified (by child age group) random sample of
      538 families raising children with disabilities in Alberta, Canada took part.
      Participants completed the Family Life Survey, which incorporated child and
      family measures, and items measuring parent implementation of home-based therapy
      regimens. RESULTS: Parents are more likely to implement therapeutic regimens when
      these are "enfolded" into other daily activities and routines. If parents have to
      "find a slot" in the daily routine to implement therapy, they will sacrifice
      personal leisure, participation in paid work, and time spent with other family
      members. Greater parent sacrifices/trade-offs was negatively associated with
      family well-being. CONCLUSION: As a general rule, children do well when their
      families do well, and families do well when they have the resources they need to
      juggle work and family and care demands. Recruiting parents as interventionists
      can tax family resources. Rehabilitation professionals must weigh up the pros and
      cons of parent-mediated intervention, and look to enfolding therapy into the
      everyday family routine.

PMID- 25073584
TI  - "Better but not best": a qualitative exploration of the experiences of
      occupational gain for people with inflammatory arthritis receiving anti-TNFalpha
      treatment.
AB  - OBJECTIVES: To investigate whether patients with improved clinical markers during
      their anti-TNFalpha treatment experience improvements in their functional and
      psychological ability to undertake activities. METHODS: Patients receiving anti
      TNFalpha treatment for rheumatoid arthritis (RA) or ankylosing spondylitis (AS)
      were recruited from outpatient clinics in East Anglia and North West England.
      Purposive sampling recruited variety in demographic and treatment experiences.
      Data were collected through in-depth qualitative interviews and analysed using an
      interpretive phenomenological framework. Twenty-seven patients were recruited; 19
      with RA, eight with AS, and aged from 21 to 73 years. RESULTS: While people
      generally experienced an improvement in their functional ability, known as
      occupational gain, they continued to experience difficulties through previous
      biomechanical damage, continuing symptoms of inflammatory arthritis, or concerns
      about anti-TNFalpha treatment. These disruptions affected how participants
      retained or regained employment. Lack of healthcare support, including an absence
      of occupational therapy intervention, resulted in people testing new boundaries
      through a process of unsupported trial and error. CONCLUSION: Occupational gain
      was not maximised for people on anti-TNFalpha treatment. Improved referral
      pathways to occupational therapy could facilitate the management of continuing
      functional difficulties, thereby maximising the benefit of treatment to people
      with inflammatory arthritis.

PMID- 25073585
TI  - Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV
      cases.
AB  - BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is an
      emerging coronavirus involved in severe acute respiratory distress syndrome
      (ARDS) and rapid renal failure. Hospital outbreak and nosocomial transmission
      were reported, however, several issues remain on the viral excretion course.
      OBJECTIVES: Describe the kinetics and pattern of viral excretion in two infected
      patients. STUDY DESIGN: After the initial diagnosis, blood, urine, rectal and
      respiratory samples were collected regularly, aliquoted and stored at -80 degrees
      C. Real-time reverse transcriptase polymerase chain reaction assay targeted the
      UpE and Orf1a regions of the MERS-CoV genome. RESULTS: In patient 1, who died of
      refractory ARDS and renal failure, MERS-CoV RNA was detected in pharyngeal and
      tracheal swabs, as well blood samples and urine samples until the 30th day.
      Rectal swabs were negative. Patient 2 also developed multiple-organ failure, but
      survived, with persisting renal insufficiency (creatinine clearance at 30 mL/min)
      and persistent interstitial syndrome albeit weaned off mechanical ventilation and
      no longer requiring oxygen. Tracheal aspirations were positive until the 33rd
      day, while nasopharyngeal swabs were negative. All other biological samples were
      negative. DISCUSSION: Lower respiratory tract excretion of MERS-CoV could be
      observed for more than one month. The most severely ill patient presented an
      expression of the virus in blood and urine, consistent with a type-1 interferon
      mediated immunological response impaired in patient 1, but developed by patient
      2. These results suggest that infection control precautions must be adequately
      evaluated in clinical wards and laboratories exposed to MERS-CoV.

PMID- 25073587
TI  - Infrared thermography to assess proliferation and involution of infantile
      hemangiomas: a prospective cohort study.
AB  - IMPORTANCE: Infantile hemangiomas (IHs) are common benign tumors of infancy that
      have the potential to interfere with vital organ function and cause permanent
      disfigurement. Currently, few objective and validated measures exist to assess
      IHs. OBJECTIVE: To determine the utility of infrared thermography in assessing
      and monitoring the growth of IHs. DESIGN, SETTING, AND PARTICIPANTS: In a
      prospective cohort study conducted at an outpatient dermatology clinic of a
      tertiary care hospital between February 2011 and December 2012, a convenience
      sample of 42 infants aged 0 to 6 months with an IH were enrolled. The mean age of
      the study group was 3.7 months, with the majority of IHs being mixed type (57%)
      affecting the head and neck (81%). Of the infants, 36 (86%) were receiving active
      treatment during the study period, and patients were followed for a minimum of 3
      clinical visits, at least 1 month apart. MAIN OUTCOMES AND MEASURES: Ability of
      infrared thermography to assess the proliferation and involution of IHs compared
      with a visual analog scale. Secondary outcomes were reliability, ease of use, and
      parental acceptance of the instrument. RESULTS: The mean temperature difference
      at baseline was 1.9 degrees F (95% CI, 1.2 degrees F to 2.7 degrees F), which
      peaked at 3 months to 2.5 degrees F (95% CI, 0.8 degrees F to 4.2 degrees F), and
      decreased progressively to 0.2 degrees F (95% CI, -1.1 degrees F to 1.4 degrees
      F) at 18.5 months (P < .001). This change in temperature was inversely correlated
      with mean visual analog scale (r = -0.25). Mean temperature differences recorded
      at baseline and 30 minutes later were not significant (least squares mean
      baseline temperature, 87.9 degrees F [95% CI, 87.4 degrees F to 88.3 degrees F],
      vs least squares mean temperature after 30 minutes, 88.1 degrees F [95% CI, 87.7
      degrees F to 88.6 degrees F] [P = .14]). Multivariate analysis demonstrated
      facial location (F(1,365) = 47.63, P < .001), IH type (F(2,365) = 3.26, P = .04),
      age (F(2,365) = 7.03, P = .001), and surface area at baseline (F(2,365) = 8.18, P
      < .001) as factors significantly affecting temperature difference over time. Only
      IH type (Wald chi(22) = 6.79, P = .03) and treatment (Wald chi(21) = 4.29, P =
      .04) significantly affected time to reach a zero-temperature difference. All
      caregivers (100%) reported IRT to be easy to implement, quick to perform, and
      comfortable for their child. CONCLUSIONS AND RELEVANCE: Infrared thermography is
      a reliable and valid measure of IH growth that is noninvasive, convenient, and
      well tolerated by infants, making it well suited to daily clinical practice. It
      has the potential to provide real-time objective results that can be used for
      routine monitoring and evaluating treatment efficacy.

PMID- 25073588
TI  - The risk of ischemic stroke after an acute myocardial infarction in patients with
      decreased renal function.
AB  - BACKGROUND: Data on the incidence, trends over time and predictors of ischemic
      stroke after an acute myocardial infarction (AMI) are sparse for patients with
      chronic kidney disease (CKD). METHODS: Data for unselected AMI patients were
      obtained from the Swedish Register of Information and Knowledge about Swedish
      Heart Intensive Care Admissions (RIKS-HIA) between 2003 and 2010. Patients with
      and without CKD were compared. Multiple logistic regression was performed to
      identify predictors of ischemic stroke during the hospitalization for AMI, Kaplan
      Meier analysis was used to analyze the 1-year postdischarge ischemic stroke
      trends over time and Cox regression analysis was used to identify predictors.
      RESULTS: Of 118,434 AMI patients, 40,679 had CKD. The CKD patients had more
      extensive previous cardiovascular disease and received less reperfusion and
      secondary preventive therapies than the patients without CKD. An inhospital
      ischemic stroke occurred in 2.3 and 1.2% of CKD and non-CKD patients,
      respectively. The incidence of ischemic stroke during hospitalization for AMI was
      stable during the study period. The occurrence of ischemic stroke after hospital
      discharge decreased between 2003-2004 and 2009-2010 from 4.1 to 2.5% in CKD
      patients and from 2.0 to 1.3% in non-CKD patients, respectively. Percutaneous
      coronary intervention (PCI) and statins were independently associated with a
      reduced risk of stroke after discharge from hospital. CONCLUSIONS: Ischemic
      stroke is a more common complication after an AMI in CKD patients than in non-CKD
      patients, but the risk has decreased in recent years. The increased use of PCI
      and statins may have contributed to this reduction.

PMID- 25073589
TI  - Visualisation of edge effects in side-gated graphene nanodevices.
AB  - Using local scanning electrical techniques we study edge effects in side-gated
      Hall bar nanodevices made of epitaxial graphene. We demonstrate that
      lithographically defined edges of the graphene channel exhibit hole conduction
      within the narrow band of ~60-125 nm width, whereas the bulk of the material is
      electron doped. The effect is the most pronounced when the influence of
      atmospheric contamination is minimal. We also show that the electronic properties
      at the edges can be precisely tuned from hole to electron conduction by using
      moderate strength electrical fields created by side-gates. However, the central
      part of the channel remains relatively unaffected by the side-gates and retains
      the bulk properties of graphene.

PMID- 25073592
TI  - NICE gives go ahead to intrabeam radiotherapy for breast cancer.

PMID- 25073593
TI  - The relationship between labour market categories and alcohol use trajectories in
      midlife.
AB  - BACKGROUND AND AIMS: Studies on the role of labour market position and change in
      alcohol use during midlife are scarce and their results are inconclusive mainly
      due to their failure to define comprehensive and distinct labour market groups
      and the short periods of time studied. In this study we used different activity
      categories for men and women to examine alcohol use trajectories in midlife
      covering a period of 17 years. METHODS: Using data from four sweeps of the
      National Child Development Study covering ages 33-50 (N=9960), we used multilevel
      growth models to study the association between labour market categories and
      longitudinal changes in weekly units of alcohol consumed. RESULTS: In the
      reference group of full-time employed men alcohol trajectory decreased over the
      follow-up period (beta=-0.14; 95% CI -0.18 to -0.11) while in the reference group
      of employed women it increased (beta=0.06; 95% CI 0.04 to 0.08). Men and women
      who were 'mainly sick' had significantly steeper declines in their alcohol
      consumption trajectory. Women who became employed after being homemakers had the
      steepest increase in alcohol use (beta=0.05; 95% CI 0.01 to 0.09). CONCLUSIONS:
      Being employed is a strong determinant of alcohol use for men and women in
      midlife, making the workplace a good target for health promotion programmes and
      policies aimed at reducing alcohol use. Caution is needed when interpreting the
      health effects of alcohol consumption as low alcohol users may have previously
      been heavy drinkers.

PMID- 25073594
TI  - Regional differences in the incidence of self-reported type 2 diabetes in
      Germany: results from five population-based studies in Germany (DIAB-CORE
      Consortium).
AB  - BACKGROUND: Population-based data are paramount to investigate the long-term
      course of diabetes, for planning in healthcare and to evaluate the cost
      effectiveness of primary prevention. We analysed regional differences in the
      incidence of self-reported type 2 diabetes mellitus in Germany. METHODS: Data of
      participants (baseline age 45-74 years) from five regional population-based
      studies conducted between 1997 and 2010 were included (mean follow-up 2.2-7.1
      years). The incidence of self-reported type 2 diabetes mellitus at follow-up was
      compared. The incidence rates per 1000 person-years (95% CI) and the cumulative
      incidence (95% CI) from regional studies were directly standardised to the German
      population (31 December 2007) and weighted by inverse probability weights for
      losses to follow-up. RESULTS: Of 8787 participants, 521 (5.9%) developed type 2
      diabetes mellitus corresponding to an incidence rate of 11.8/1000 person-years
      (95% CI 10.8 to 12.9). The regional incidence was highest in the East and lowest
      in the South of Germany with 16.9 (95% CI 13.3 to 21.8) vs 9.3 (95% CI 7.4 to
      11.1)/1000 person-years, respectively. The incidence increased with age and was
      higher in men than in women. CONCLUSIONS: The incidence of self-reported type 2
      diabetes mellitus shows regional differences within Germany. Prevention measures
      need to consider sex-specific differences and probably can be more efficiently
      introduced toward those regions in need.

PMID- 25073595
TI  - Added value of hybrid myocardial perfusion SPECT and CT coronary angiography in
      the diagnosis of coronary artery disease.
AB  - AIMS: Hybrid single photon emission computed tomography (SPECT)/coronary computed
      tomography angiography (CCTA) has only been evaluated for its diagnostic accuracy
      as a single test in patients suspected of significant coronary artery disease
      (CAD). Added value of hybrid SPECT/CCTA beyond usual clinical work-up, or use of
      each of these tests separately, remains unclear. We evaluated the added value of
      hybrid myocardial perfusion SPECT (SPECT) and CCTA, beyond pre-test likelihood
      and exercise stress ECG (X-ECG), in the diagnosis of CAD. METHODS AND RESULTS:
      Two hundred and five patients with stable angina pectoris and intermediate-to
      high pre-test likelihood were prospectively included. All patients underwent
      clinical history and examination, X-ECG, stress and rest SPECT, coronary calcium
      scoring (CCS) and CCTA. Fractional flow reserve measurement <0.80 or a lesion
      >50% on coronary angiography (CA) served as reference standard for significant
      CAD. Multiple imputation was used to correct for missing test results (17-20%).
      Added value of hybrid SPECT/CCTA to the basic model of pre-test likelihood plus X
      ECG was quantified using logistic regression analysis. Model differences were
      then assessed using differences in C-index and in net reclassification
      improvement (NRI). The basic model had a C-index of 0.73 (95%CI 0.66-0.80). This
      significantly increased to 0.85 (95%CI 0.80-0.91) by addition of only SPECT, to
      0.90 (95%CI 0.85-0.94) when adding only CCTA, and to 0.96 (95%CI 0.92-0.99) when
      adding hybrid SPECT/CCTA. The accompanying NRIs were 0.82 (95%CI 0.62-1.02), 0.86
      (95%CI 0.66-1.06) and 1.57 (95%CI 1.11-1.59) respectively. CONCLUSION: Current
      analysis resembles clinical routine of layered testing and shows that hybrid
      SPECT/CCTA imaging has a substantially higher yield than standalone SPECT or CCTA
      in the diagnostic workup of patients suspected of significant CAD.

PMID- 25073596
TI  - Anomalous connection of the left upper pulmonary vein to the vertical vein: an
      uncommon diagnosis unveiled by suprasternal notch imaging.

PMID- 25073597
TI  - Accuracy of a computer-based diagnostic program for ambulatory patients with knee
      pain.
AB  - BACKGROUND: Looking up information regarding a medical condition is the third
      most popular activity online, and there are a variety of web-based symptom
      checking programs available to the patient. However, the authors are not aware of
      any that have been scientifically evaluated as an accurate measure for the cause
      of one's knee pain. PURPOSE/HYPOTHESIS: The purpose of this study was to design
      and evaluate an Internet-based program that generates a differential diagnosis
      based on a history of knee pain entered by the patient. The hypothesis was that
      the program would accurately generate a differential diagnosis for patients
      presenting with knee pain. STUDY DESIGN: Cohort study (diagnosis); Level of
      evidence, 2. METHODS: A web-based program was created to collect knee pain
      history and generate a differential diagnosis for ambulatory patients with knee
      pain. The program selected from 26 common knee diagnoses. A total of 527
      consecutive patients aged >=18 years, who presented with a knee complaint to 7
      different board-certified orthopaedic surgeons during a 3-month period, were
      asked to complete the questionnaire in the program. Upon completion, patients
      were examined by a board-certified orthopaedic surgeon. Both the patient and
      physician were blinded to the differential diagnosis generated by the program. A
      third party was responsible for comparing the diagnosis(es) generated by the
      program with that determined by the physician. The level of matching between
      diagnoses determined the accuracy of the program. RESULTS: A total of 272 male
      and 255 female patients, with an average age of 47 years (range, 18-84 years),
      participated in the study. The median number of diagnoses generated by the
      program was 4.8 (range, 1-10), with this list containing the physician's
      diagnosis(es) 89% of the time. The specificity was 27%. CONCLUSION: Despite a low
      specificity, the results of this study show the program to be an accurate method
      for generating a differential diagnosis for knee pain.

PMID- 25073598
TI  - Platelet-rich plasma injections for the treatment of hamstring injuries: a
      randomized controlled trial.
AB  - BACKGROUND: A hamstring injury is one of the most common types of injury
      affecting athletes. Despite this, the optimal management of hamstring muscle
      injuries is not yet defined. The effect of autologous platelet-rich plasma (PRP)
      therapy on the recovery of hamstring injuries is unclear. PURPOSE: To investigate
      the effect of a single PRP injection in the treatment of grade 2 hamstring muscle
      injuries. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2.
      METHODS: Twenty-eight patients diagnosed with an acute hamstring injury were
      randomly allocated to autologous PRP therapy combined with a rehabilitation
      program or a rehabilitation program only. The primary outcome of this study was
      time to return to play. In addition, changes in pain severity and pain
      interference scores over time were examined. RESULTS: Patients in the PRP group
      achieved full recovery significantly earlier than controls (P = .02). The mean
      time to return to play was 26.7 +/- 7.0 days and 42.5 +/- 20.6 days for the PRP
      and control groups, respectively (t(22) = 2.50, P = .02). [corrected].
      Significantly lower pain severity scores were observed in the PRP group
      throughout the study. However, no significant difference in the pain interference
      score was found between the 2 groups. CONCLUSION: A single autologous PRP
      injection combined with a rehabilitation program was significantly more effective
      in treating hamstring injuries than a rehabilitation program alone.

PMID- 25073599
TI  - Identification and replication of a combined epigenetic and genetic biomarker
      predicting suicide and suicidal behaviors.
AB  - Considerable research suggests that suicide involves effects of genes, the
      environment, and their interaction. Analysis of three independent data sets of
      post-mortem brains revealed signs of increased methylation in one particular
      gene, SKA2, a finding that was extended to peripheral blood samples from other
      cohorts of prospectively followed individuals. 

PMID- 25073602
TI  - Mathematical modeling of light-mediated HPA axis activity and downstream
      implications on the entrainment of peripheral clock genes.
AB  - In this work we propose a semimechanistic model that describes the photic signal
      transduction to the hypothalamic-pituitary-adrenal (HPA) axis that ultimately
      regulates the synchronization of peripheral clock genes (PCGs). Our HPA axis
      model predicts that photic stimulation induces a type-1 phase response curve to
      cortisol's profile with increased cortisol sensitivity to light exposure in its
      rising phase, as well as the shortening of cortisol's period as constant light
      increases (Aschoff's first rule). Furthermore, our model provides insight into
      cortisol's phase and amplitude dependence on photoperiods and reveals that
      cortisol maintains highest amplitude variability when it is entrained by a
      balanced schedule of light and dark periods. Importantly, by incorporating the
      links between HPA axis and PCGs we were able to investigate how cortisol
      secretion impacts the entrainment of a population of peripheral cells and show
      that disrupted light schedules, leading to blunted cortisol secretion, fail to
      synchronize a population of PCGs which further signifies the loss of circadian
      rhythmicity in the periphery of the body. 

PMID- 25073600
TI  - Translation in solid cancer: are size-based response criteria an anachronism?
AB  - The purpose of translation is the development of effective medicinal products
      based on validated science. A parallel objective is to obtain marketing
      authorization for the translated product. Unfortunately, in solid cancer, these
      two objectives are not mutually consistent as evidenced by the contrast between
      major advances in science and the continuing dismal record of pharmaceutical
      productivity. If the problem is unrelated to science, then the process of
      translation may require a closer examination, namely, the criteria for regulatory
      approval. This realization is important because, in this context, the objective
      of translation is regulatory approval, and science does not passively translate
      into useful medicinal products. Today, in solid cancer, response criteria related
      to tumor size are less useful than during the earlier cytotoxic drugs era;
      advanced imaging and biomarkers now allow for tracking of the natural history of
      the disease in the laboratory and the clinic. Also, it is difficult to infer
      clinical benefit from tumor shrinkage since it is rarely sustained. Accordingly,
      size-based response criteria may represent an anachronism relative to translation
      in solid cancer and it may be appropriate to align preclinical and clinical
      effort and shift the focus to local invasion and metastasis. The shift from a
      cancer cell-centric model to a stroma centric model offers novel opportunities
      not only to interupt the natural history of the disease, but also to rethink the
      relevance of outdated criteria of clinical response. Current evidence favors the
      opinion that, in solid cancer, a different, broader, and contextual approach may
      lead to interventions that could delay local invasion and metastasis. All
      elements supporting this shift, especially advanced imaging, are in place. 

PMID- 25073601
TI  - Effects of mtDNA in SHR-mtF344 versus SHR conplastic strains on reduced OXPHOS
      enzyme levels, insulin resistance, cardiac hypertrophy, and systolic dysfunction.
AB  - Common inbred strains of the laboratory rat can be divided into four major
      mitochondrial DNA (mtDNA) haplotype groups represented by the BN, F344, LEW, and
      SHR strains. In the current study, we investigated the metabolic and hemodynamic
      effects of the SHR vs. F344 mtDNA by comparing the SHR vs. SHR-mt(F344)
      conplastic strains that are genetically identical except for their mitochondrial
      genomes. Altogether 13 amino acid substitutions in protein coding genes, seven
      single nucleotide polymorphisms in tRNA genes, and 12 single nucleotide changes
      in rRNA genes were detected in F344 mtDNA compared with SHR mtDNA. Analysis of
      oxidative phosphorylation system (OXPHOS) in heart left ventricles (LV), muscle,
      and liver revealed reduced activity and content of several respiratory chain
      complexes in SHR-mt(F344) conplastic rats compared with the SHR strain. Lower
      function of OXPHOS in LV of conplastic rats was associated with significantly
      increased relative ventricular mass and reduced fractional shortening that was
      independent of blood pressure. In addition, conplastic rats exhibited reduced
      sensitivity of skeletal muscles to insulin action and impaired glucose tolerance.
      These results provide evidence that inherited alterations in mitochondrial
      genome, in the absence of variation in the nuclear genome and other confounding
      factors, predispose to insulin resistance, cardiac hypertrophy and systolic
      dysfunction. 

PMID- 25073603
TI  - Structural changes in the gut microbiome of constipated patients.
AB  - Previous studies using culture-based methods suggested an association between
      constipation and altered abundance of certain taxa of the colonic microbiome. We
      aim to examine the global changes in gut microbial composition of constipated
      patients. A cross-sectional pilot study using 16S rRNA gene pyrosequencing was
      performed to compare stool microbial composition of eight constipated patients
      and 14 nonconstipated controls. Only obese children were enrolled so that the
      microbiome features associated with constipation would not be obscured by those
      associated with obesity. The sequencing reads were processed by QIIME for
      quantitative analysis of the microbial composition at genus and above levels.
      Dietary intake for all the individuals was assessed by dietary recalls and a food
      frequency questionnaire. The ecological diversities of fecal microbiome of the
      constipated patients differed from those of the controls. Significantly decreased
      abundance in Prevotella and increased representation in several genera of
      Firmicutes were observed in constipated patients compared with controls. The
      conventional probiotic genera Lactobacillus and Bifidobacteria were not decreased
      in the microbiomes of the constipated patients. These alterations in the fecal
      microbiome of constipated patients suggested that a novel probiotic treatment
      including certain Prevotella strains may be more effective than conventional
      probiotic products incorporating Lactobacillus or Bifidobacterium species. While
      it is possible that the observed changes in the microbiome in constipated
      subjects are a consequence of a low-fiber diet, these changes also predict a
      different pattern of bacterial fermentation end-products, such as increased
      butyrate production, which may contribute to pathogenesis of constipation. 

PMID- 25073604
TI  - Differentially co-expressed genes in postmortem prefrontal cortex of individuals
      with alcohol use disorders: influence on alcohol metabolism-related pathways.
AB  - Chronic alcohol consumption may induce gene expression alterations in brain
      reward regions such as the prefrontal cortex (PFC), modulating the risk of
      alcohol use disorders (AUDs). Transcriptome profiles of 23 AUD cases and 23
      matched controls (16 pairs of males and 7 pairs of females) in postmortem PFC
      were generated using Illumina's HumanHT-12 v4 Expression BeadChip. Probe-level
      differentially expressed genes and gene modules in AUD subjects were identified
      using multiple linear regression and weighted gene co-expression network
      analyses. The enrichment of differentially co-expressed genes in alcohol
      dependence-associated genes identified by genome-wide association studies (GWAS)
      was examined using gene set enrichment analysis. Biological pathways
      overrepresented by differentially co-expressed genes were uncovered using DAVID
      bioinformatics resources. Three AUD-associated gene modules in males [Module 1
      (561 probes mapping to 505 genes): r = 0.42, P(correlation) = 0.020; Module 2
      (815 probes mapping to 713 genes): r = 0.41, P(correlation) = 0.020; Module 3
      (1,446 probes mapping to 1,305 genes): r = -0.38, P(correlation) = 0.030] and one
      AUD-associated gene module in females [Module 4 (683 probes mapping to 652
      genes): r = 0.64, P(correlation) = 0.010] were identified. Differentially
      expressed genes mapped by significant expression probes (P(nominal) <= 0.05)
      clustered in Modules 1 and 2 were enriched in GWAS-identified alcohol dependence
      associated genes [Module 1 (134 genes): P = 0.028; Module 2 (243 genes): P =
      0.004]. These differentially expressed genes, including ALDH2, ALDH7A1, and
      ALDH9A1, are involved in cellular functions such as aldehyde detoxification,
      mitochondrial function, and fatty acid metabolism. Our study revealed
      differentially co-expressed genes in postmortem PFC of AUD subjects and
      demonstrated that some of these differentially co-expressed genes participate in
      alcohol metabolism.

PMID- 25073605
TI  - Cervical cancer: barriers to screening in the Somali community in Minnesota.
AB  - This study examined barriers to and facilitators of cervical cancer screening
      among Somali immigrant women in Minnesota. We adopted the socioecological
      framework to illustrate screening barriers at multiple levels. We conducted 23
      semi-structured key informant interviews and used a thematic exploratory approach
      to analyze the data. Barriers were classified into individual, community or
      health systems levels. Obstacles included lack of knowledge, religious beliefs,
      fatalism, fear, embarrassment, and lack of trust in the interpreters.
      Participants described a need for training of healthcare providers on issues
      surrounding Somali women's cultural practices and sexual health. Identifying
      individual, community, or health system barriers and addressing them concurrently
      may increase use of cancer screening services among Somali women. Future
      interventions need to address multilevel barriers with multilevel approaches to
      improve utilization of cervical cancer screening services in underserved
      immigrant populations in the United States. 

PMID- 25073606
TI  - Automated palpation for breast tissue discrimination based on viscoelastic
      biomechanical properties.
AB  - PURPOSE: Accurate, noninvasive methods are sought for breast tumor detection and
      diagnosis. In particular, a need for noninvasive techniques that measure both the
      nonlinear elastic and viscoelastic properties of breast tissue has been
      identified. For diagnostic purposes, it is important to select a nonlinear
      viscoelastic model with a small number of parameters that highly correlate with
      histological structure. However, the combination of conventional viscoelastic
      models with nonlinear elastic models requires a large number of parameters. A
      nonlinear viscoelastic model of breast tissue based on a simple equation with few
      parameters was developed and tested. METHODS: The nonlinear viscoelastic
      properties of soft tissues in porcine breast were measured experimentally using
      fresh ex vivo samples. Robotic palpation was used for measurements employed in a
      finite element model. These measurements were used to calculate nonlinear
      viscoelastic parameters for fat, fibroglandular breast parenchyma and muscle. The
      ability of these parameters to distinguish the tissue types was evaluated in a
      two-step statistical analysis that included Holm's pairwise [Formula: see text]
      test. The discrimination error rate of a set of parameters was evaluated by the
      Mahalanobis distance. RESULTS: Ex vivo testing in porcine breast revealed
      significant differences in the nonlinear viscoelastic parameters among
      combinations of three tissue types. The discrimination error rate was low among
      all tested combinations of three tissue types. CONCLUSION: Although tissue
      discrimination was not achieved using only a single nonlinear viscoelastic
      parameter, a set of four nonlinear viscoelastic parameters were able to reliably
      and accurately discriminate fat, breast fibroglandular tissue and muscle.

PMID- 25073608
TI  - Polling the readers of Skeletal Radiology.

PMID- 25073607
TI  - Inflammation and psychopathology: what we now know, and what we need to know.

PMID- 25073609
TI  - An electron transfer series of octahedral chromium complexes containing a redox
      non-innocent alpha-diimine ligand.
AB  - An electron-transfer series of octahedral alpha-diimine complexes
      [((H)L(Cy))3Cr](n+)(BARF)n (n = 2, 1, 0) has been synthesized and
      crystallographically characterized. Cyclic voltammetry indicated additional
      formation of [((H)L(Cy))3Cr](3+). The molecular structures suggested that all
      redox processes were ligand-based. Magnetic moments were consistent with spin
      ground states of S = 0 for [(H)L(Cy)3Cr](0), S = 1/2 for [(H)L(Cy)3Cr](+1), and S
      = 1 for [(H)L(Cy)3Cr](+2). The experimental data is consistent with chromium
      maintaining the +III oxidation state throughout, while being coordinated by
      varying numbers of neutral diimines ((H)L(Cy)) and diimine radical anions
      ((H)L(Cy)(-)). 

PMID- 25073610
TI  - How priming in visual search affects response time distributions: analyses with
      ex-Gaussian fits.
AB  - Although response times (RTs) are the dependent measure of choice in the majority
      of studies of visual attention, changes in RTs can be hard to interpret. First,
      they are inherently ambiguous, since they may reflect a change in the central
      tendency or skew (or both) of a distribution. Second, RT measures may lack
      sensitivity, since meaningful changes in RT patterns may not be picked up if they
      reflect two or more processes having opposing influences on mean RTs. Here we
      describe RT distributions for repetition priming in visual search, fitting ex
      Gaussian functions to RT distributions. We focus here on feature and conjunction
      search tasks, since priming effects in these tasks are often thought to reflect
      similar mechanisms. As expected, both tasks resulted in strong priming effects
      when target and distractor identities repeated, but a large difference between
      feature and conjunction search was also seen, in that the sigma parameter
      (reflecting the standard deviation of the Gaussian component) was far more
      affected by search repetition in conjunction than in feature search. Although
      caution should clearly be used when particular parameter estimates are matched to
      specific functions or processes, our results suggest that analyses of RT
      distributions can inform theoretical accounts of priming in visual search tasks,
      in this case showing quite different repetition effects for the two differing
      search types, suggesting that priming in the two paradigms partly reflects
      different mechanisms. 

PMID- 25073611
TI  - Stimulus- and goal-driven control of eye movements: action videogame players are
      faster but not better.
AB  - Action videogame players (AVGPs) have been shown to outperform nongamers (NVGPs)
      in covert visual attention tasks. These advantages have been attributed to
      improved top-down control in this population. The time course of visual
      selection, which permits researchers to highlight when top-down strategies start
      to control performance, has rarely been investigated in AVGPs. Here, we addressed
      specifically this issue through an oculomotor additional-singleton paradigm.
      Participants were instructed to make a saccadic eye movement to a unique
      orientation singleton. The target was presented among homogeneous nontargets and
      one additional orientation singleton that was more, equally, or less salient than
      the target. Saliency was manipulated in the color dimension. Our results showed
      similar patterns of performance for both AVGPs and NVGPs: Fast-initiated saccades
      were saliency-driven, whereas later-initiated saccades were more goal-driven.
      However, although AVGPs were faster than NVGPs, they were also less accurate.
      Importantly, a multinomial model applied to the data revealed comparable
      underlying saliency-driven and goal-driven functions for the two groups. Taken
      together, the observed differences in performance are compatible with the
      presence of a lower decision bound for releasing saccades in AVGPs than in NVGPs,
      in the context of comparable temporal interplay between the underlying
      attentional mechanisms. In sum, the present findings show that in both AVGPs and
      NVGPs, the implementation of top-down control in visual selection takes time to
      come about, and they argue against the idea of a general enhancement of top-down
      control in AVGPs.

PMID- 25073612
TI  - Visual memory performance for color depends on spatiotemporal context.
AB  - Performance on visual short-term memory for features has been known to depend on
      stimulus complexity, spatial layout, and feature context. However, with few
      exceptions, memory capacity has been measured for abruptly appearing, single
      instance displays. In everyday life, objects often have a spatiotemporal history
      as they or the observer move around. In three experiments, we investigated the
      effect of spatiotemporal history on explicit memory for color. Observers saw a
      memory display emerge from behind a wall, after which it disappeared again. The
      test display then emerged from either the same side as the memory display or the
      opposite side. In the first two experiments, memory improved for intermediate set
      sizes when the test display emerged in the same way as the memory display. A
      third experiment then showed that the benefit was tied to the original motion
      trajectory and not to the display object per se. The results indicate that memory
      for color is embedded in a richer episodic context that includes the
      spatiotemporal history of the display. 

PMID- 25073613
TI  - Presence of comorbidity affects both treatment strategies and outcomes in disease
      activity, physical function, and quality of life in patients with rheumatoid
      arthritis.
AB  - To clarify the impact of comorbidities on treatment strategies and outcomes in
      patients with rheumatoid arthritis (RA) using a large observational RA cohort,
      the presence of comorbidities was assessed using the Charlson Comorbidity Index
      (CCI). Changes in medication, disease activity by Disease Activity Score-28 joint
      count (DAS28) over 6 months, disability assessed by the Japanese version of the
      Health Assessment Questionnaire (J-HAQ), and quality of life by EuroQOL-5
      Dimensions (EQ-5D) over 1 year in patients with high disease activity (DAS28 >
      5.1) at baseline were assessed according to age-adjusted CCI (CCI(A)) and
      categorized into four groups (CCI(A) 0, 1-2, 3-4, and >=5). Among 5,317 patients,
      975 patients (18.3%) had at least one comorbidity listed by CCI. DAS28, J-HAQ,
      and EQ-5D increased in severity with increased CCI(A) levels. Among patients with
      high disease activity (n = 267), treatment with methotrexate and/or biologics and
      improved DAS28 scores, shown by attenuated intensity, were associated with
      increased CCI(A) levels. J-HAQ improved from 1.29 +/- 0.31 to 0.87 +/- 0.37 in 1
      year in the CCI(A) 0 group. The adjusted difference (standard error) in J-HAQ at
      1 year in CCI(A) 1-2, 3-4, and >=5 groups was worse than J-HAQ in the CCI(A) 0
      group by 0.32 (0.09, p < 0.001), 0.45 (0.10, p < 0.001), and 0.45 (0.15, p <
      0.01), respectively. The magnitude of improvement of EQ-5D was significantly
      attenuated with increasing CCI(A) levels. Thus, patients with comorbidities may
      not experience the same degree of benefit from recent RA treatments compared with
      patients without comorbidities in daily practice.

PMID- 25073615
TI  - Inflammation and macrophage modulation in adipose tissues.
AB  - The adipose tissue is an active endocrine organ that harbours not only mature and
      developing adipocytes but also a wide array of immune cells, including
      macrophages, a key immune cell in determining metabolic functionality. With
      adipose tissue expansion, M1 pro-inflammatory macrophage infiltration increases,
      activates other immune cells, and affects lipid trafficking and metabolism, in
      part via inhibiting mitochondrial function and increasing reactive oxygen species
      (ROS). The pro-inflammatory cytokines produced and released interfere with
      insulin signalling, while inhibiting M1 macrophage activation improves systemic
      insulin sensitivity. In healthy adipose tissue, M2 alternative macrophages
      predominate and associate with enhanced lipid handling and mitochondrial
      function, anti-inflammatory cytokine production, and inhibition of ROS. The
      sequence of events leading to macrophage infiltration and activation in adipose
      tissue remains incompletely understood but lipid handling of both macrophages and
      adipocytes appears to play a major role.

PMID- 25073614
TI  - Ultrasound assessment of enthesis thickening in psoriatic arthritis patients
      treated with adalimumab compared to methotrexate.
AB  - The objective of the study was to combine ultrasonographic (US) with clinical
      findings for comparing the effect of adalimumab (ADA) to methotrexate (MTX) on
      the thickness of tendons and enthesis in psoriatic arthritis (PsA) patients.
      Forty-three consecutive PsA patients were examined at baseline and after 6 and 12
      weeks of treatment with ADA or MTX. The US assessment included thickness
      measurement of the extensor (ET) and flexor tendons (FT) of the second and third
      finger of both hands, plantar aponeurosis (PA) and the Achilles tendon (AT)
      bilaterally. Disease activity (DA) was assessed by the number of tender (TJ) and
      swollen joints (SJ), the number of inflamed enthesis (IE), pain assessment (PAI),
      and patient (PDAI) and physician (PHDAI) disease activity evaluations by visual
      activity score (VAS). Nineteen patients received MTX and 24 patients received
      ADA. All DA parameters improved in both groups. A decrease in thickness of
      tendons and enthesis was observed only in the ADA group, reaching a level of
      significance for the left AT (p = 0.01), left PA (p = 0.007), the second left FT
      (p = 0.04) and the third ET (p = 0.04). ADA patients showed a trend towards a
      better response to treatment compared to MTX patients that reach significance at
      week 6 of treatment for the thickness of left AT (p = 0.04), left PA (p = 0.03),
      the number of TJ (p = 0.0136), PAI (p = 0.0028), and PDAI (p = 0.029). ADA
      treatment for PsA compared to MTX significantly improved signs of DA and several
      US parameters. US assessment of enthesis can be an additional useful tool in the
      monitoring of psoriatic enthesopathy.

PMID- 25073616
TI  - Microbial and metabolic characterization of a denitrifying phosphorus-uptake/side
      stream phosphorus removal system for treating domestic sewage.
AB  - In this study, an advanced wastewater treatment process, the denitrifying
      phosphorus/side stream phosphorus removal system (DPR-Phostrip), was developed
      for the purpose of enhancing denitrifying phosphorus removal. The enrichment of
      denitrifying phosphorus-accumulating organisms (DPAOs) and the microbial
      community structure of DPR-Phostrip were evaluated by polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE), and the metabolic activity of
      seed sludge and activated sludge collected after 55 days of operation were
      evaluated by BiologTM analysis. This experimental study of DPR-Phostrip operation
      showed that nutrients were removed effectively, and denitrifying phosphorus
      removal was observed during the pre-anoxic period. PCR-DGGE analysis indicated
      that DPR-Phostrip supported DPAO growth while inhibiting PAOs and GAOs. The major
      dominant species in DPR-Phostrip were Bacteroidetes bacterium, Saprospiraceae
      bacterium, and Chloroflexi bacterium. Moreover, the functional diversity indices
      calculated on the basis of Biolog analysis indicated that DPR-Phostrip had almost
      no effect on microbial community diversity but was associated with a shift in the
      dominant species, which confirms the results of the PCR-DGGE analysis. The
      results for average well color development, calculated via Biolog analysis,
      showed that DPR-Phostrip had a little impact on the metabolic activity of sludge.
      Further principal component analysis suggested that the ability to utilize low
      molecular-weight organic compounds was reduced in DPR-Phostrip.

PMID- 25073617
TI  - ACL injuries and stem cell therapy.
AB  - Tears of the anterior cruciate ligament (ACL) are very frequent injuries,
      particularly in young and active people. Arthroscopic reconstruction using tendon
      auto- or allograft represents the gold-standard for the management of ACL tears.
      Interestingly, the ACL has the potential to heal upon intensive non-surgical
      rehabilitation procedures. Several biological factors influence this healing
      process as local intraligamentous cytokines and mainly cell repair mechanisms
      controlled by stem cells or progenitor cells. Understanding the mechanisms of
      this regeneration process and the cells involved may pave the way for novel, less
      invasive and biology-based strategies for ACL repair. This review aims to focus
      on the current knowledge on the mechanisms of ACL healing, the nature and
      potential of ligament derived stem/progenitor cells as well as on the potential
      and the limitations of using mesenchymal stem cells (MSCs) for treating injured
      ACL. 

PMID- 25073618
TI  - Injurious mechanical ventilation causes kidney apoptosis and dysfunction during
      sepsis but not after intra-tracheal acid instillation: an experimental study.
AB  - BACKGROUND: Intratracheal aspiration and sepsis are leading causes of acute lung
      injury that frequently necessitate mechanical ventilation (MV), which may
      aggravate lung injury thereby potentially increasing the risk of acute kidney
      injury (AKI). We compared the effects of ventilation strategies and underlying
      conditions on the development of AKI. METHODS: Spraque Dawley rats were
      challenged by intratracheal acid instillation or 24 h of abdominal sepsis,
      followed by MV with a low tidal volume (LVT) and 5 cm H2O positive end-expiratory
      pressure (PEEP) or a high tidal volume (HVT) and no PEEP, which is known to cause
      more lung injury after acid instillation than in sepsis. Rats were ventilated for
      4 hrs and kidney function and plasma mediator levels were measured. Kidney injury
      was assessed by microscopy; apoptosis was quantified by TUNEL staining. RESULTS:
      During sepsis, but not after acid instillation, MV with HVT caused more renal
      apoptosis than MV with LVT. Increased plasma active plasminogen activator
      inhibitor-1 correlated to kidney apoptosis in the cortex and medulla. Increased
      apoptosis after HVT ventilation during sepsis was associated with a 40% decrease
      in creatinine clearance. CONCLUSIONS: AKI is more likely to develop after MV
      induced lung injury during an indirect (as in sepsis) than after a direct (as
      after intra-tracheal instillation) insult to the lungs, since it induces kidney
      apoptosis during sepsis but not after acid instillation, opposite to the lung
      injury it caused. Our findings thus suggest using protective ventilatory
      strategies in human sepsis, even in the absence of overt lung injury, to protect
      the kidney.

PMID- 25073619
TI  - "These issues aren't talked about at home": a qualitative study of the sexual and
      reproductive health information preferences of adolescents in Vanuatu.
AB  - BACKGROUND: Onset of sexual activity during adolescence is common in Vanuatu,
      however access to comprehensive sexual and reproductive health (SRH) information
      is limited. Improving adolescents' knowledge about SRH is necessary to improve
      health outcomes, however little is known about the information needs and
      preferences of adolescents in the Pacific to inform policy and programs in this
      region. METHODS: Sixty-six focus group discussions were conducted with 341 male
      and female adolescents aged 15-19 years from rural and urban communities on two
      islands of Vanuatu. Twelve key-informant interviews were also conducted with
      policymakers and health service providers. Data were analysed thematically using
      an inductive approach. RESULTS: Much of the SRH information targeting adolescents
      focused on sexually transmitted infections and HIV. While this information was
      valued, important gaps were identified including prevention of pregnancy, condom
      use, puberty, sexuality and relationships. Peer educators and health workers were
      adolescents' preferred sources of information because they were considered
      knowledgeable and trustworthy. Parents were not a common source but were
      preferred, particularly by girls, despite considerable socio-cultural barriers.
      Schools were an important but underutilised source of information, as were a
      range of media sources. CONCLUSIONS: Providing adolescents with comprehensive SRH
      information can have life-long protective benefits, however there are important
      content gaps in information currently provided in Vanuatu. The broad range of
      sources preferred by adolescents highlights the need to strengthen information
      provision through multiple channels to reach in and out-of-school youth and
      respond to individual needs and contexts.

PMID- 25073620
TI  - Diagnostic accuracy of rapid urine dipstick test to predict urinary tract
      infection among pregnant women in Felege Hiwot Referral Hospital, Bahir Dar,
      North West Ethiopia.
AB  - BACKGROUND: Untreated bacteriuria during pregnancy has been shown to be
      associated with low birth-weight and premature delivery. Therefore, routine
      screening for bacteriuria is advocated. The decision about how to screen pregnant
      women for bacteriuria has always been a balance between the cost of screening
      versus the sensitivity and specificity. This study was designed to evaluate the
      diagnostic accuracy of the rapid dipstick test to predict urinary tract infection
      in pregnancy against the gold standard urine culture. METHOD: A total of 367 mid
      stream urine samples were collected, inoculated on MacConkey, Manitol salt agar
      (MSA) and blood agar and incubated aerobically at 37 degrees C for overnight.
      Specimens were classified as "positive" for urinary tract infection (UTI) if the
      growth of the pathogen(s) was at a count >= 10(5) colony-forming units per
      milliliter (cfu/mL) of urine and classified as "negative" with growth of <10(5)
      cfu/mL. Urine samples were tested for the presence of nitrite and leukocyte
      esterase using dipstick rapid test in accordance to the manufacturer's
      instructions. RESULTS: From the total study participants, 37 pregnant women were
      symptomatic and the remaining 330 pregnant women were asymptomatic. The
      sensitivity and specificity of dipstick tests of leukocyte esterase was 50% and
      89.1% for pregnant women with asymptomatic UTI(ABU) and 71.4% and 86.7% for
      symptomatic UTI respectively and for nitrite 35.7% and 98.0% for ABU and 57.1%
      and 96.7% symptomatic UTI. CONCLUSION: This study revealed that the use of
      dipstick leukocyte esterase and nitrite for screening UTI particularly
      asymptomatic bacteriuria was associated with many false positive and negative
      results when it was compared against the gold standard culture method. The low
      sensitivity and positive predictive value of urine dipstick test proved that
      culture should be used for the diagnosis of UTI.

PMID- 25073622
TI  - Single mutations in ABCA3 increase the risk for neonatal respiratory distress
      syndrome in late preterm infants (gestational age 34-36 weeks).

PMID- 25073623
TI  - Algorithms for quantitative quasi-static elasticity imaging using force data.
AB  - Quasi-static elasticity imaging can improve diagnosis and detection of diseases
      that affect the mechanical behavior of tissue. In this methodology, images of the
      shear modulus of the tissue are reconstructed from the measured displacement
      field. This is accomplished by seeking the spatial distribution of mechanical
      properties that minimizes the difference between the predicted and the measured
      displacement fields, where the former is required to satisfy a finite element
      approximation to the equations of equilibrium. In the absence of force data, the
      shear modulus is determined only up to a multiplicative constant. In this
      manuscript, we address the problem of calibrating quantitative elastic modulus
      reconstructions created from measurements of quasi-static deformations. We
      present two methods that utilize the knowledge of the applied force on a portion
      of the boundary. The first involves rescaling the shear modulus of the original
      minimization problem to best match the measured force data. This approach is
      easily implemented but neglects the spatial distribution of tractions. The second
      involves adding a force-matching term to the original minimization problem and a
      change of variables wherein we seek the log of the shear modulus. We present
      numerical results that demonstrate the usefulness of both methods.

PMID- 25073624
TI  - Periodontal cytokines profile under orthodontic force and extracorporeal shock
      wave stimuli in a rat model.
AB  - BACKGROUND AND OBJECTIVE: Extracorporeal shock wave therapy has been used in
      various clinical conditions as a result of its ability to stimulate healing
      processes in acute and chronic inflammatory states. Orthodontic force application
      triggers an inflammatory reaction in the periodontal tissue surrounding the
      involved teeth, resulting in tooth movement. Preliminary work revealed that
      extracorporeal shock wave therapy increased the expression of the inflammatory
      cytokines involved. Our aim was to investigate the expression of inflammatory
      cytokines in the periodontal tissues following orthodontic force induction, with
      and without shock wave therapy, in experimental rats. MATERIAL AND METHODS: An
      orthodontic appliance was fabricated and applied between the molars and the
      incisors of adult Wistar rats. In conjunction with orthodontic force
      commencement, the rats were treated with a single episode of 1000 shock waves.
      Every day, during the 3 d of the study, rats were killed and the
      immunolocalization of RANKL, interleukin (IL)-1beta, IL-6 and tumor necrosis
      factor-alpha was evaluated. RESULTS: The percentage of the area staining
      positively for all inflammatory cytokines during the first 2 d decreased
      statistically significantly more in the shock wave-treated group compared with
      the nontreated control group. On the first day, the percentage of the area
      staining positively for IL-1beta and RANKL on the compression side peaked in both
      groups, with a sequential rise in the number of TRAP-positive cells. CONCLUSION:
      The induction of shock wave therapy during orthodontic tooth movement influences
      the expression of different inflammatory cytokines in the tissue and might alter
      the expected periodontal remodeling rate.

PMID- 25073625
TI  - Follow-up to abnormal cancer screening tests: considering the multilevel context
      of care.
AB  - The call for multilevel interventions to improve the quality of follow-up to
      abnormal cancer screening has been out for a decade, but published work
      emphasizes individual approaches, and conceptualizations differ regarding the
      definition of levels. To investigate the scope and methods being undertaken in
      this focused area of follow-up to abnormal tests (breast, colon, cervical), we
      reviewed recent literature and grants (2007-2012) funded by the National Cancer
      Institute. A structured search yielded 16 grants with varying definitions of
      "follow-up" (e.g., completion of recommended tests, time to diagnosis); most
      included minority racial/ethnic group participants. Ten grants concentrated on
      measurement/intervention development and 13 piloted or tested interventions
      (categories not mutually exclusive). All studies considered patient-level factors
      and effects. Although some directed interventions at provider levels, few
      measured group characteristics and effects of interventions on the providers or
      levels other than the patient. Multilevel interventions are being proposed, but
      clarity about endpoints, definition of levels, and measures is needed. The
      differences in the conceptualization of levels and factors that affect practice
      need empirical exploration, and we need to measure their salient characteristics
      to advance our understanding of how context affects cancer care delivery in a
      changing practice and policy environment.

PMID- 25073626
TI  - Downregulation of microRNAs 145-3p and 145-5p is a long-term predictor of
      postmenopausal breast cancer risk: The ORDET prospective study.
AB  - BACKGROUND: miRNAs have been implicated in the regulation of key metabolic,
      inflammatory, and malignant pathways; hence, they might be considered both
      predictors and players of cancer development. METHODS: Using a case-control study
      design nested in the ORDET prospective cohort study, we addressed the possibility
      that specific mRNAs can serve as early predictors of breast cancer incidence in
      postmenopausal women. We compared leukocyte miRNA profiles of 133 incident
      postmenopausal breast cancer cases and profiles of 133 women who remained healthy
      over a follow-up period of 20 years. RESULTS: The analysis identified 20
      differentially expressed miRNAs, 15 of which were downregulated. Of the 20
      miRNAs, miR145-5p and miR145-3p, each derived from another arm of the respective
      pre-miRNA, were consistently and significantly downregulated in all the databases
      that we surveyed. For example, analysis of more than 1,500 patients (the UK
      Metabric cohort) indicated that high abundance of miR145-3p and miR145-5p was
      associated with longer, and for miR145-3p also statistically significant,
      survival. The experimental data attributed different roles to the identified
      miRNAs: Although the 5p isoform was associated with invasion and metastasis, the
      other isoform seems related to cell proliferation. CONCLUSIONS: These
      observations and the prospective design of our study lend support to the
      hypothesis that downregulation of specific miRNAs constitutes an early event in
      cancer development. This finding might be used for breast cancer prevention.
      IMPACT: The identification of the miRNAs as long-term biomarkers of breast cancer
      may have an impact on breast cancer prevention and early detection.

PMID- 25073627
TI  - Quantitative determination of seven chemical constituents and chemo-type
      differentiation of chamomiles using high-performance thin-layer chromatography.
AB  - A simple and rapid high-performance thin-layer chromatographic method was
      developed for the separation and determination of six flavonoids (rutin, luteolin
      7-O-beta-glucoside, chamaemeloside, apigenin-7-O-beta-glucoside, luteolin,
      apigenin) and one coumarin, umbelliferone from chamomile plant samples and
      dietary supplements. The separation was achieved on amino silica stationary phase
      using dichloromethane/acetonitrile/ethyl formate/glacial acetic acid/formic acid
      (11:2.5:3:1.25:1.25 v/v/v/v/v) as the mobile phase. The quantitation of each
      compound was carried out using densitometric reflection/absorption mode at their
      respective absorbance maxima after postchromatographic derivatization using
      natural products reagent (1% w/v methanolic solution of diphenylboric acid-beta
      ethylamino ester). The method was validated for specificity, limits of detection
      and quantification, precision (intra- and interday) and accuracy. The limits of
      detection and quantification were found to be in the range from 6-18 and 16-55
      ng/band for six flavonoids and one coumarin, respectively. The intra- and
      interday precision was found to be <5% RSD and recovery of all the compounds was
      >90%. The data acquired from high-performance thin-layer chromatography was
      processed by principal component analysis using XLSTAT statistical software.
      Application of principal component analysis and agglomerative hierarchial
      clustering was successfully able to differentiate two chamomiles (German and
      Roman) and Chrysanthemum.

PMID- 25073628
TI  - Correlates of objectively measured sedentary behavior in cancer patients with
      brain metastases: an application of the theory of planned behavior.
AB  - OBJECTIVE: The aim of this study is to examine the demographic, medical, and
      social-cognitive correlates of objectively measured sedentary behavior in
      advanced cancer patients with brain metastases. METHODS: Advanced cancer patients
      diagnosed with brain metastases, aged 18 years or older, cognitively intact, and
      with palliative performance scale greater than 30%, were recruited from a Rapid
      Access Palliative Radiotherapy Program multidisciplinary brain metastases clinic.
      A cross-sectional survey interview assessed the theory of planned behavior
      variables and medical and demographic information. Participants wore activPALTM
      (PAL Technologies Ltd, Glasgow, United Kingdom) accelerometers recording time
      spent supine, sitting, standing, and stepping during 7 days encompassing
      palliative whole brain radiotherapy treatments. RESULTS: Thirty-one patients were
      recruited. Correlates of median time spent supine or sitting in hours per day
      were instrumental attitude (i.e., perceived benefits) of physical activity (r = 
      0.42; p = 0.030) and affective attitude (i.e., perceived enjoyment) of physical
      activity (r = -0.43; p = 0.024). Moreover, participants who sat or were supine
      for greater than 20.7 h per day reported significantly lower instrumental
      attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.051) and affective attitude (M = 0.7;
      95% CI = 0.0-1.4; p = 0.041). Finally, participants who were older than 60 years
      of age spent more time sitting or being supine. CONCLUSIONS: Instrumental
      attitude and affective attitude were the strongest correlates of objectively
      measured sedentary behavior. This information could inform intervention studies
      to increase physical activity in advanced cancer patients with brain metastases.

PMID- 25073629
TI  - The clinical value of peak nasal inspiratory flow, peak oral inspiratory flow,
      and the nasal patency index.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to ascertain the most reliable
      objective measurement for the assessment of nasal patency by investigating the
      relationship between peak nasal inspiratory flow, peak oral inspiratory flow, and
      the nasal patency index in relation to the patient's subjective perception
      regarding nasal obstruction. STUDY DESIGN: Prospective cohort study. METHODS:
      This study included 131 volunteers of both genders, aged 18 years or older, with
      or without nasal symptoms, who were able to give informed consent, completed the
      study protocol, and could speak and write Dutch fluently. Peak nasal inspiratory
      flow and peak oral inspiratory flow were performed and nasal patency index was
      computed. The results were evaluated and compared with the subjective perception
      of nasal passage, using the validated Nasal Obstruction Symptom Evaluation scale
      and visual analog scale for nasal passage. RESULTS: Our study showed that peak
      nasal inspiratory flow, nasal patency index and nasal patency visual analog scale
      correlate with the Nasal Obstruction Symptom Evaluation scale in contrast to peak
      oral inspiratory flow. Peak nasal inspiratory flow and nasal patency index also
      showed significant association with the Nasal Obstruction Symptom Evaluation
      scale after adjustment for confounders. CONCLUSIONS: Peak nasal inspiratory flow
      is the most reliable method for the assessment of nasal patency. It is quick,
      inexpensive, and easy to perform, and correlates significantly with the
      subjective feeling of nasal obstruction. There is no clinical need to measure
      peak oral inspiratory flow or to calculate the nasal patency index in the
      evaluation of nasal patency. LEVEL OF EVIDENCE: 4

PMID- 25073630
TI  - Education and Imaging. Gastroenterology: a bleeding colonic Dieulafoy lesion
      successfully detected by colonoscopy using a transparent hood.

PMID- 25073631
TI  - Education and Imaging. Gastroenterology: mesenteric lymphoma with chylous
      ascites.

PMID- 25073632
TI  - Education and Imaging. Gastroenterology: acute mucosal injury of esophagus and
      stomach induced by sodium picosulfate/magnesium citrate for bowel preparation.

PMID- 25073633
TI  - Education and Imaging. Hepatobiliary and pancreatic: systemic mastocytosis with
      portal hypertension.

PMID- 25073634
TI  - Education and Imaging. Hepatobiliary and pancreatic: hepatic focal fatty
      infiltration mimicking hepatocellular carcinoma.

PMID- 25073636
TI  - Clinical evaluation of apex locator and radiography in primary teeth.
AB  - AIM: The aim of this in vivo study was to evaluate the accuracy and reliability
      of electronic apex locater and radiographic determination of root canal length in
      primary teeth. METHODOLOGY: A total of 32 human primary molar teeth (96 roots)
      were selected. After endodontic access preparation, root canals were irrigated
      with physiological saline solution. The access cavities were dried with cotton
      pellets and, the roots were dried with paper points before performing the
      electronic measurement. The root canal length measurements were first taken with
      an apex locater (EndoMaster), and then, a size ? 15 K-file was inserted into the
      root canal, and radiography was taken to determine the working length
      measurements. The measurement data were recorded and compared by one-way anova
      and Kruskal-Wallis tests. P < 0.05 was accepted for the significance. RESULTS:
      The mean values for radiography were 13.23 +/- 1.92 mm and for EndoMaster were
      13.08 +/- 1.77 mm. The accuracy of EndoMaster was 80.2% in correct measurements
      +/-1 mm (P < 0.001). CONCLUSION: The electronic apex locators could be useful in
      determining working length and thereby decreasing the need for radiographs and
      exposure to ionizing radiation in pediatric dental patients.

PMID- 25073635
TI  - Vascularized bone transplant chimerism mediated by vascular endothelial growth
      factor.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) induces angiogenesis and
      osteogenesis in bone allotransplants. We aim to determine whether bone remodeling
      in VEGF-treated bone allotransplants results from repopulation with circulation
      derived autogenous cells or survival of allogenic transplant-derived cells.
      METHODS: Vascularized femoral bone transplants were transplanted from female Dark
      Agouti rats (DA;RT1(a) ) to male Piebald Viral Glaxo (PVG;RT1(c) ). Arteriovenous
      bundle implantation and short-term immunosuppression were used to maintain
      cellular viability. VEGF was encapsulated in biodegradable microspheres and
      delivered intramedullary in the experimental group (n = 22). In the control group
      (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser
      capture microdissection of bone remodeling areas was performed at the inner and
      outer cortex. Sex-mismatched genes were quantified with reverse transcription
      polymerase chain reaction to determine the amount of male cells to total cells,
      defined as the relative expression ratio (rER). RESULTS: At 4 weeks, rER was
      significantly higher at the inner cortex in VEGF-treated transplants as compared
      to untreated transplants (0.622 +/- 0.225 vs. 0.362 +/- 0.081, P = 0.043). At 4
      weeks, the outer cortex in the control group had a significantly higher rER (P =
      0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015).
      Over time, in the outer cortex the rER significantly increased to 0.634 +/- 0.106
      at 18 weeks in VEGF-treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at
      all cortical areas in both groups. CONCLUSIONS: These in vivo findings suggest a
      chemotactic effect of intramedullary applied VEGF on recipient-derived bone and
      could imply that more rapid angiogenesis of vascularized allotransplants can be
      established with microencapsulated VEGF.

PMID- 25073637
TI  - High risk of pulmonary embolism and deep venous thrombosis but not of stroke in
      granulomatosis with polyangiitis (Wegener's).
AB  - OBJECTIVE: To assess the incidence of stroke, pulmonary embolism (PE), and deep
      venous thrombosis (DVT) in granulomatosis with polyangiitis (Wegener's) (GPA).
      METHODS: Patients diagnosed with GPA at a Danish tertiary care center during 1993
      2011 were identified (n = 180). Each patient was matched with 19 population
      controls (n = 3,420). Information on hospitalizations for stroke, PE, and DVT was
      obtained from the Danish National Hospital Register. The occurrence of vascular
      events in the GPA cohort was compared with that in the control group by
      calculation of incidence rate ratios (IRRs). RESULTS: The median duration of
      followup was 7.2 years (interquartile range 3.1-11.7 years) in the GPA cohort.
      Within the first 2 years following the diagnosis of vasculitis, the incidences of
      PE and DVT were substantially increased among the patients (IRR 25.7 [95%
      confidence interval (95% CI) 6.9-96] for PE and IRR 20.2 [95% CI 5.1-81] for
      DVT). The incidence of stroke was not increased during this time interval (IRR
      1.4 [95% CI 0.3-5.7]). From 2 years after GPA diagnosis, an increased incidence
      was found for DVT (IRR 4.5 [95% CI 1.7-11.8]) but not for PE (IRR 1.3 [95% CI 0.2
      9.6]) or stroke (IRR 1.4 [95% CI 0.6-3.3]). In the GPA cohort, 70% of the
      vascular events occurred during phases with active vasculitis. CONCLUSION: The
      present study confirms that GPA patients have a markedly increased risk of venous
      thromboembolism. We did not observe an increased risk of stroke in our cohort.
      Thus, our observations demonstrate a differential impact of GPA and/or its
      treatment on the risk of various vascular events.

PMID- 25073639
TI  - The effect of the 'Gait keeper' mutation in the DMRT3 gene on gaiting ability in
      Icelandic horses.
AB  - A nonsense mutation in DMRT3 ('Gait keeper' mutation) has a predominant effect on
      gaiting ability in horses, being permissive for the ability to perform lateral
      gaits and having a favourable effect on speed capacity in trot. The DMRT3 mutant
      allele (A) has been found in high frequency in gaited breeds and breeds bred for
      harness racing, while other horse breeds were homozygous for the wild-type allele
      (C). The aim of this study was to evaluate further the effect of the DMRT3
      nonsense mutation on the gait quality and speed capacity in the multigaited
      Icelandic horse and demonstrate how the frequencies of the A- and C- alleles have
      changed in the Icelandic horse population in recent decades. It was confirmed
      that homozygosity for the DMRT3 nonsense mutation relates to the ability to pace.
      It further had a favourable effect on scores in breeding field tests for the
      lateral gait tolt, demonstrated by better beat quality, speed capacity and
      suppleness. Horses with the CA genotype had on the other hand significantly
      higher scores for walk, trot, canter and gallop, and they performed better beat
      and suspension in trot and gallop. These results indicate that the AA genotype
      reinforces the coordination of ipsilateral legs, with the subsequent negative
      effect on the synchronized movement of diagonal legs compared with the CA
      genotype. The frequency of the A-allele has increased in recent decades with a
      corresponding decrease in the frequency of the C-allele. The estimated frequency
      of the A-allele in the Icelandic horse population in 2012 was 0.94. Selective
      breeding for lateral gaits in the Icelandic horse population has apparently
      altered the frequency of DMRT3 genotypes with a predicted loss of the C-allele in
      relatively few years. The results have practical implications for breeding and
      training of Icelandic horses and other gaited horse breeds. 

PMID- 25073638
TI  - Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin
      metabolism suggest association with cerebrospinal fluid monoamine metabolite
      concentrations in psychosis.
AB  - BACKGROUND: Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3
      methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in the
      central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations,
      reflecting the monoamine turnover rates in CNS, are partially under genetic
      influence and have been associated with schizophrenia. We have hypothesized that
      CSF monoamine metabolite concentrations represent intermediate steps between
      single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic
      pathways and psychosis. METHODS: We have searched for association between 119
      SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1
      (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta
      hydroxylase (DBH), catechol-O-methyltransferase (COMT), monoamine oxidase A
      (MAOA) and MAOB] and monoamine metabolite concentrations in CSF in 74 patients
      with psychotic disorder. RESULTS: There were 42 nominally significant
      associations between SNPs and CSF monoamine metabolite concentrations, which
      exceeded the expected number (20) of nominal associations given the total number
      of tests performed. The strongest association (p = 0.0004) was found between MAOB
      rs5905512, a SNP previously reported to be associated with schizophrenia in men,
      and MHPG concentrations in men with psychotic disorder. Further analyses in 111
      healthy individuals revealed that 41 of the 42 nominal associations were
      restricted to patients with psychosis and were absent in healthy controls.
      CONCLUSIONS: The present study suggests that altered monoamine turnover rates in
      CNS reflect intermediate steps in the associations between SNPs and psychosis.

PMID- 25073640
TI  - Antivirulence activity of the human gut metabolome.
AB  - The mammalian gut contains a complex assembly of commensal microbes termed
      microbiota. Although much has been learned about the role of these microbes in
      health, the mechanisms underlying these functions are ill defined. We have
      recently shown that the mammalian gut contains thousands of small molecules, most
      of which are currently unidentified. Therefore, we hypothesized that these
      molecules function as chemical cues used by hosts and microbes during their
      interactions in health and disease. Thus, a search was initiated to identify
      molecules produced by the microbiota that are sensed by pathogens. We found that
      a secreted molecule produced by clostridia acts as a strong repressor of
      Salmonella virulence, obliterating expression of the Salmonella pathogenicity
      island 1 as well as host cell invasion. It has been known for decades that the
      microbiota protects its hosts from invading pathogens, and these data suggest
      that chemical sensing may be involved in this phenomenon. Further investigations
      should reveal the exact biological role of this molecule as well as its
      therapeutic potential. Importance: Microbes can communicate through the
      production and sensing of small molecules. Within the complex ecosystem formed by
      commensal microbes living in and on the human body, it is likely that these
      molecular messages are used extensively during the interactions between different
      microbial species as well as with host cells. Deciphering such a molecular
      dialect will be fundamental to our understanding of host-microbe interactions in
      health and disease and may prove useful for the design of new therapeutic
      strategies that target these mechanisms of communication.

PMID- 25073641
TI  - Antigen export during liver infection of the malaria parasite augments protective
      immunity.
AB  - Protective immunity against preerythrocytic malaria parasite infection is
      difficult to achieve. Intracellular Plasmodium parasites likely minimize antigen
      presentation by surface-expressed major histocompatibility complex class I (MHC
      I) molecules on infected cells, yet they actively remodel their host cells by
      export of parasite factors. Whether exported liver-stage proteins constitute
      better candidates for MHC-I antigen presentation to CD8(+) T lymphocytes remains
      unknown. Here, we systematically characterized the contribution of protein export
      to the magnitude of antigen-specific T-cell responses against Plasmodium berghei
      liver-stage parasites in C57BL/6 mice. We generated transgenic sporozoites that
      secrete a truncated ovalbumin (OVA) surrogate antigen only in the presence of an
      amino-terminal protein export element. Immunization with live attenuated
      transgenic sporozoites revealed that antigen export was not critical for CD8(+) T
      cell priming but enhanced CD8(+) T-cell proliferation in the liver. Upon transfer
      of antigen-specific CD8(+) T cells, liver-stage parasites secreting the target
      protein were eliminated more efficiently. We conclude that Plasmodium parasites
      strictly control protein export during liver infection to minimize immune
      recognition. Strategies that enhance the discharge of parasite proteins into
      infected hepatocytes could improve the efficacy of candidate preerythrocytic
      malaria vaccines. Importance: Vaccine development against Plasmodium parasites
      remains a priority in malaria research. The most advanced malaria subunit vaccine
      candidates contain Plasmodium surface proteins with important roles for parasite
      vital functions. A fundamental question is whether recognition by effector CD8(+)
      T cells is restricted to sporozoite surface antigens or extends to parasite
      proteins that are synthesized during the extensive parasite expansion phase in
      the liver. Using a surrogate model antigen, we found that a cytoplasmic antigen
      is able to induce robust protective CD8(+) T-cell responses, but protein export
      further enhances immunogenicity and protection. Our results show that a
      cytoplasmic localization does not exclude a protein's candidacy for malaria
      subunit vaccines and that protein secretion can enhance protective immunity.

PMID- 25073642
TI  - Inactivation of thyA in Staphylococcus aureus attenuates virulence and has a
      strong impact on metabolism and virulence gene expression.
AB  - Staphylococcus aureus thymidine-dependent small-colony variants (TD-SCVs) are
      frequently isolated from patients with chronic S. aureus infections after long
      term treatment with trimethoprim-sulfamethoxazole (TMP-SMX). While it has been
      shown that TD-SCVs were associated with mutations in thymidylate synthase (TS;
      thyA), the impact of such mutations on protein function is lacking. In this
      study, we showed that mutations in thyA were leading to inactivity of TS
      proteins, and TS inactivity led to tremendous impact on S. aureus physiology and
      virulence. Whole DNA microarray analysis of the constructed DeltathyA mutant
      identified severe alterations compared to the wild type. Important virulence
      regulators (agr, arlRS, sarA) and major virulence determinants (hla, hlb, sspAB,
      and geh) were downregulated, while genes important for colonization (fnbA, fnbB,
      spa, clfB, sdrC, and sdrD) were upregulated. The expression of genes involved in
      pyrimidine and purine metabolism and nucleotide interconversion changed
      significantly. NupC was identified as a major nucleoside transporter, which
      supported growth of the mutant during TMP-SMX exposure by uptake of extracellular
      thymidine. The DeltathyA mutant was strongly attenuated in virulence models,
      including a Caenorhabditis elegans killing model and an acute pneumonia mouse
      model. This study identified inactivation of TS as the molecular basis of
      clinical TD-SCV and showed that thyA activity has a major role for S. aureus
      virulence and physiology. Importance: Thymidine-dependent small-colony variants
      (TD-SCVs) of Staphylococcus aureus carry mutations in the thymidylate synthase
      (TS) gene (thyA) responsible for de novo synthesis of thymidylate, which is
      essential for DNA synthesis. TD-SCVs have been isolated from patients treated for
      long periods with trimethoprim-sulfamethoxazole (TMP-SMX) and are associated with
      chronic and recurrent infections. In the era of community-associated methicillin
      resistant S. aureus, the therapeutic use of TMP-SMX is increasing. Today, the
      emergence of TD-SCVs is still underestimated due to misidentification in the
      diagnostic laboratory. This study showed for the first time that mutational
      inactivation of TS is the molecular basis for the TD-SCV phenotype and that TS
      inactivation has a strong impact on S. aureus virulence and physiology. Our study
      helps to understand the clinical nature of TD-SCVs, which emerge frequently once
      patients are treated with TMP-SMX.

PMID- 25073643
TI  - Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak
      clusters through both sexual macroevolution and asexual microevolution.
AB  - An outbreak of the fungal pathogen Cryptococcus gattii began in the Pacific
      Northwest (PNW) in the late 1990s. This outbreak consists of three clonal
      subpopulations: VGIIa/major, VGIIb/minor, and VGIIc/novel. Both VGIIa and VGIIc
      are unique to the PNW and exhibit increased virulence. In this study, we
      sequenced the genomes of isolates from these three groups, as well as global
      isolates, and analyzed a total of 53 isolates. We found that VGIIa/b/c
      populations show evidence of clonal expansion in the PNW. Whole-genome sequencing
      provided evidence that VGIIb originated in Australia, while VGIIa may have
      originated in South America, and these were likely independently introduced.
      Additionally, the VGIIa outbreak lineage may have arisen from a less virulent
      clade that contained a mutation in the MSH2 ortholog, but this appears to have
      reverted in the VGIIa outbreak strains, suggesting that a transient mutator
      phenotype may have contributed to adaptation and evolution of virulence in the
      PNW outbreak. PNW outbreak isolates share genomic islands, both between the
      clonal lineages and with global isolates, indicative of sexual recombination.
      This suggests that VGII C. gattii has undergone sexual reproduction, either
      bisexual or unisexual, in multiple locales contributing to the production of
      novel, virulent subtypes. We also found that the genomes of two basal VGII
      isolates from HIV(+) patients contain an introgression tract spanning three
      genes. Introgression substantially contributed to intra-VGII polymorphism and
      likely occurred through sexual reproduction with VGI. More broadly, these
      findings illustrate how both microevolution and sexual reproduction play central
      roles in the development of infectious outbreaks from avirulent or less virulent
      progenitors. Importance: Cryptococcus gattii is the causative agent responsible
      for ongoing infections in the Pacific Northwest of the United States and western
      Canada. The incidence of these infections increased dramatically in the 1990s and
      remains elevated. These infections are attributable to three clonal lineages of
      C. gattii, VGIIa, VGIIb, and VGIIc, with only VGIIa identified once previously in
      the Pacific Northwest prior to the start of the outbreak, albeit in a less
      virulent form. This study addresses the origin and emergence of this outbreak,
      using whole-genome sequencing and comparison of both outbreak and global
      isolates. We show that VGIIa arose mitotically from a less virulent clonal group,
      possibly via the action of a mutator phenotype, while VGIIb was likely introduced
      from Australia, and VGIIc appears to have emerged in the United States or in an
      undersampled locale via sexual reproduction. This work shows that multiple
      processes can contribute to the emergence of an outbreak.

PMID- 25073645
TI  - The emergence of bacterial "hopeful monsters".
AB  - The global spread of antibiotic-resistant bacteria has largely been driven by the
      dissemination of successful lineages. A particularly important example is
      sequence type (ST) 258 of Klebsiella pneumoniae, a common cause of health care
      associated infections. Representatives of this lineage carry a variable array of
      plasmid-borne resistance genes, typically including a carbapenemase effective
      against the full range of clinically important beta-lactams. In their recent mBio
      article, Chen et al. [mBio 5(3):e01355-14] described how ST258 emerged through
      "hybridization" between two other strains, with a second recombination resulting
      in the diversification of a key antigen. This commentary describes the findings
      in the context of other examples where saltational evolution has resulted in the
      sudden emergence of important pathogenic bacteria. 

PMID- 25073644
TI  - Host-directed antimicrobial drugs with broad-spectrum efficacy against
      intracellular bacterial pathogens.
AB  - We sought a new approach to treating infections by intracellular bacteria,
      namely, by altering host cell functions that support their growth. We screened a
      library of 640 Food and Drug Administration (FDA)-approved compounds for agents
      that render THP-1 cells resistant to infection by four intracellular pathogens.
      We identified numerous drugs that are not antibiotics but were highly effective
      in inhibiting intracellular bacterial growth with limited toxicity to host cells.
      These compounds are likely to target three kinds of host functions: (i) G protein
      coupled receptors, (ii) intracellular calcium signals, and (iii) membrane
      cholesterol distribution. The compounds that targeted G protein receptor
      signaling and calcium fluxes broadly inhibited Coxiella burnetii, Legionella
      pneumophila, Brucella abortus, and Rickettsia conorii, while those directed
      against cholesterol traffic strongly attenuated the intracellular growth of C.
      burnetii and L. pneumophila. These pathways probably support intracellular
      pathogen growth so that drugs that perturb them may be therapeutic candidates.
      Combining host- and pathogen-directed treatments is a strategy to decrease the
      emergence of drug-resistant intracellular bacterial pathogens. Importance:
      Although antibiotic treatment is often successful, it is becoming clear that
      alternatives to conventional pathogen-directed therapy must be developed in the
      face of increasing antibiotic resistance. Moreover, the costs and timing
      associated with the development of novel antimicrobials make repurposed FDA
      approved drugs attractive host-targeted therapeutics. This paper describes a
      novel approach of identifying such host-targeted therapeutics against
      intracellular bacterial pathogens. We identified several FDA-approved drugs that
      inhibit the growth of intracellular bacteria, thereby implicating host
      intracellular pathways presumably utilized by bacteria during infection.

PMID- 25073647
TI  - Development and testing of a field diagnostic assay for peste des petits
      ruminants virus.
AB  - We have developed an immunochromatographic test for the diagnosis of peste des
      petits ruminants (PPR) under field conditions. The diagnostic assay has been
      tested in the laboratory and also under field conditions in Ivory Coast,
      Pakistan, Ethiopia and Uganda. The test is carried out on a superficial swab
      sample (ocular or nasal) and showed a sensitivity of 84% relative to PCR. The
      specificity was 95% over all nasal and ocular samples. The test detected as
      little as 10(3) TCID50 (50% tissue culture infectious doses) of cell culture
      grown virus, and detected virus isolates representing all four known genetic
      lineages of peste des petits ruminants virus. Virus could be detected in swabs
      from animals as early as 4 days post-infection, at a time when clinical signs
      were minimal. Feedback from field trials was uniformly positive, suggesting that
      this diagnostic tool may be useful for current efforts to control the spread of
      PPR. 

PMID- 25073648
TI  - Narrowband ultraviolet B phototherapy in combination with other therapies for
      vitiligo: mechanisms and efficacies.
AB  - Vitiligo is a disorder of pigmentation affecting about 1% of the global
      population. It is a psychologically devastating disease with suboptimal treatment
      options. Narrowband ultraviolet B (NB-UVB) phototherapy has become a first-line
      choice for treating generalized disease. In recent years, topical calcineurin
      inhibitors, vitamin D analogues, antioxidant agents and other therapies have been
      combined with NB-UVB to improve its efficacy. This article will address what is
      known about the mechanisms of action of these treatments and how they may
      complement NB-UVB on a cellular level, as well as offer a comprehensive, evidence
      based review of clinical outcomes with combination therapies.

PMID- 25073650
TI  - Comparative genome sequencing to assess the genetic diversity and virulence
      attributes of 15 Vibrio anguillarum isolates.
AB  - Vibrio anguillarum is the causative agent of vibriosis, a deadly haemorrhagic
      septicaemic disease affecting various marine and fresh/brackish water fish,
      bivalves and crustaceans. However, the diversity and virulence mechanisms of this
      pathogen are still insufficiently known. In this study, we aimed to increase our
      understanding of V. anguillarum diversity and virulence through comparative
      genome analysis of 15 V. anguillarum strains, obtained from different hosts or
      non-host niches and geographical regions, among which 10 and 5 strains were found
      to be virulent and avirulent, respectively, against sea bass larvae. First, the
      15 draft genomes were annotated and screened for putative virulence factors,
      including genes encoding iron uptake systems, transport systems and non-ribosomal
      peptide synthetases. Second, comparative genome analysis was performed, focusing
      on single nucleotide polymorphisms (SNPs) and small insertions and deletions
      (InDels). Five V. anguillarum strains showed a remarkably high nucleotide
      identity. However, these strains comprise both virulent and avirulent strains
      towards sea bass larvae, suggesting that differences in virulence may be caused
      by subtle nucleotide variations. Clearly, the draft genome sequence of these 15
      strains represents a starting point for further genetic research of this
      economically important fish pathogen. 

PMID- 25073649
TI  - Epigenetics in the perioperative period.
AB  - The perioperative period is characterized by profound changes in the body's
      homoeostatic processes. This review seeks to address whether epigenetic
      mechanisms may influence an individual's reaction to surgery and anaesthesia.
      Evidence from animal and human studies suggests that epigenetic mechanisms can
      explain many facets of susceptibility to acute and chronic pain, making them
      potential therapeutic targets. Modern pain management is still based upon
      opiates, and both the developmental expression of opioid receptors and opioid
      induced hyperalgesia have been linked to epigenetic mechanisms. In general,
      opiates seem to increase global DNA methylation levels. This is in contrast to
      local anaesthetics, which have been ascribed a global demethylating effect. Even
      though no direct investigations have been carried out, the potential influence of
      epigenetics on the inflammatory response that follows surgery seems a promising
      area for research. There is a considerable body of evidence that supports the
      involvement of epigenetics in the complex process of wound healing. Epigenetics
      is an important emerging research topic in perioperative medicine, with a huge
      potential to positively influence patient outcome.

PMID- 25073651
TI  - Associations between IL-1RA polymorphisms and small intestinal bacterial
      overgrowth among patients with irritable bowel syndrome from India.
AB  - BACKGROUND: Low-grade inflammation (controlled by pro and anti-inflammatory
      molecules), induced by gut microbes in patients with small intestinal bacterial
      overgrowth (SIBO), may be associated with irritable bowel syndrome (IBS).
      Polymorphisms of IL-RA gene (anti-inflammatory) was evaluated in IBS and healthy
      subjects (HS); small intestinal mucosal IL-1alpha and beta levels (pro
      inflammatory) in relation to the presence of SIBO were evaluated in a subset of
      patients. METHODS: Two hundred and twenty-one IBS patients and 273 age- and
      gender-matched HS were included. Exactly 209 of 221 patients (Rome III) and 273
      HS were genotyped (PCR) for IL-1RA polymorphism. Mucosal IL-1alpha and beta
      levels (pg/mg of biopsy) were estimated (ELISA) in 82/221 patients with and
      without SIBO (>=10(5)  CFU/mL upper gut aspirate bacteria). KEY RESULTS: Genotype
      1/1 (IL-1RA over-producer) was less frequent among patients than controls (p =
      0.007); genotypes 1/3 (p = 0.012, OR = 3.301, 95% CI = 1.31-8.35) and 2/3 (both
      under-producers; p = 0.009, OR = 7.703, 95% CI = 1.66-35.82) were commoner among
      IBS. Fifteen of 82 (18.3%) patients had SIBO. Levels of IL-1alpha and beta were
      higher among patients with SIBO than without (IL-1alpha: 35.4 [20.1-66.8] vs 25.5
      [4.2-65.3], p < 0.001; IL-1beta: 206.8 [133.5-365.9] vs 93.1 [25.5-197.7], p <
      0.001) and those with bloating than without (p = 0.012; p = 0.015). IL-1beta was
      higher among patients with Bristol stool type 6 than those with type 1-2 (p =
      0.002) and type 3-5 (p = 0.007). CONCLUSIONS & INFERENCES: Polymorphisms 1/1 (IL
      1RA over-producer) was infrequent and 1/3 and 2/3 (under-producers) frequent
      among IBS. Increased IL-1alpha and beta levels were associated with SIBO.
      Increased IL-1beta level was predominantly associated with bloating and loose
      stools (Bristol type 6).

PMID- 25073652
TI  - Modelling recurrent events: comparison of statistical models with continuous and
      discontinuous risk intervals on recurrent malaria episodes data.
AB  - BACKGROUND: Recurrent events data analysis is common in biomedicine. Literature
      review indicates that most statistical models used for such data are often based
      on time to the first event or consider events within a subject as independent.
      Even when taking into account the non-independence of recurrent events within
      subjects, data analyses are mostly done with continuous risk interval models,
      which may not be appropriate for treatments with sustained effects (e.g., drug
      treatments of malaria patients). Furthermore, results can be biased in cases of a
      confounding factor implying different risk exposure, e.g. in malaria
      transmission: if subjects are located at zones showing different environmental
      factors implying different risk exposures. METHODS: This work aimed to compare
      four different approaches by analysing recurrent malaria episodes from a clinical
      trial assessing the effectiveness of three malaria treatments [artesunate +
      amodiaquine (AS + AQ), artesunate + sulphadoxine-pyrimethamine (AS + SP) or
      artemether-lumefantrine (AL)], with continuous and discontinuous risk intervals:
      Andersen-Gill counting process (AG-CP), Prentice-Williams-Peterson counting
      process (PWP-CP), a shared gamma frailty model, and Generalized Estimating
      Equations model (GEE) using Poisson distribution. Simulations were also made to
      analyse the impact of the addition of a confounding factor on malaria recurrent
      episodes. RESULTS: Using the discontinuous interval analysis, AG-CP and Shared
      gamma frailty models provided similar estimations of treatment effect on malaria
      recurrent episodes when adjusted on age category. The patients had significant
      decreased risk of recurrent malaria episodes when treated with AS + AQ or AS + SP
      arms compared to AL arm; Relative Risks were: 0.75 (95% CI (Confidence Interval):
      0.62-0.89), 0.74 (95% CI: 0.62-0.88) respectively for AG-CP model and 0.76 (95%
      CI: 0.64-0.89), 0.74 (95% CI: 0.62-0.87) for the Shared gamma frailty model.With
      both discontinuous and continuous risk intervals analysis, GEE Poisson
      distribution models failed to detect the effect of AS + AQ arm compared to AL arm
      when adjusted for age category. The discontinuous risk interval analysis was
      found to be the more appropriate approach. CONCLUSION: Repeated event in
      infectious diseases such as malaria can be analysed with appropriate existing
      models that account for the correlation between multiple events within subjects
      with common statistical software packages, after properly setting up the data
      structures.

PMID- 25073653
TI  - Separation of oil from a water/oil mixed drop using two nonparallel plates.
AB  - In this work, we have developed a simple approach to separate oil from a
      microliter-scaled water/oil mixture by squeezing the mixture using two
      nonparallel plates. Three pairs of plates with Teflon, SU-8, and SiO2 coatings,
      respectively, are used in the tests, and all of these plates are capable of
      separating the water/oil mixed drops. 95.5% silicone oil and 97.0% light mineral
      oil have been collected from their corresponding mixtures with water through the
      pair of Teflon plates. Furthermore, on the basis of pressure difference inside a
      liquid drop, theoretical models have been developed to interpret the
      corresponding mechanisms of the separation process, as well as the observed
      phenomena. To judge whether two immiscible liquids could be separated using the
      developed approach, a sufficient condition has also been derived, which includes
      three theoretical relations. The sufficient condition is subsequently validated
      by experiments. This condition also provides criteria for choosing a good plate
      coating. Such a coating should ensure (i) the oil wets the plate surface with a
      relatively large contact angle, and has small contact angle hysteresis, and (ii)
      the advancing contact angle that the water/oil interface forms on the plate
      surface is larger than 90 degrees . 

PMID- 25073655
TI  - Deaths: preliminary data for 2008.
AB  - Objectives-This report presents preliminary U.S. data on deaths, death rates,
      life expectancy, leading causes of death, and infant mortality for 2008 by
      selected characteristics such as age, sex, race, and Hispanic origin. Methods
      Data in this report are based on death records comprising more than 99 percent of
      the demographic and medical files for all deaths in the United States in 2008.
      The records are weighted to independent control counts for 2008. For certain
      causes of death such as unintentional injuries, homicides, suicides, drug-induced
      deaths, and sudden infant death syndrome, preliminary and final data may differ
      because of the truncated nature of the preliminary file. Comparisons are made
      with 2007 final data. Results-The age-adjusted death rate decreased from 760.2
      deaths per 100,000 population in 2007 to 758.7 deaths per 100,000 population in
      2008. From 2007 to 2008, age-adjusted death rates decreased significantly for 6
      of the 15 leading causes of death: Diseases of heart, Malignant neoplasms,
      Cerebrovascular diseases, Accidents (unintentional injuries), Diabetes mellitus,
      andAssault (homicide). From 2007 to 2008, age-adjusted death rates increased
      significantly for 6 of the 15 leading causes of death: Chronic lower respiratory
      diseases; Alzheimer's disease; Influenza and pneumonia; Nephritis, nephrotic
      syndrome and nephrosis; Intentional self-harm (suicide); and Essential
      hypertension and hypertensive renal disease. Life expectancy decreased by 0.1
      year from 77.9 years in 2007 to 77.8 in 2008. 

PMID- 25073654
TI  - Dextran as a generally applicable multivalent scaffold for improving
      immunoglobulin-binding affinities of peptide and peptidomimetic ligands.
AB  - Molecules able to bind the antigen-binding sites of antibodies are of interest in
      medicine and immunology. Since most antibodies are bivalent, higher affinity
      recognition can be achieved through avidity effects in which a construct
      containing two or more copies of the ligand engages both arms of the
      immunoglobulin simultaneously. This can be achieved routinely by immobilizing
      antibody ligands at high density on solid surfaces, such as ELISA plates, but
      there is surprisingly little literature on scaffolds that routinely support
      bivalent binding of antibody ligands in solution, particularly for the important
      case of human IgG antibodies. Here we show that the simple strategy of linking
      two antigens with a polyethylene glycol (PEG) spacer long enough to span the two
      arms of an antibody results in higher affinity binding in some, but not all,
      cases. However, we found that the creation of multimeric constructs in which
      several antibody ligands are displayed on a dextran polymer reliably provides
      much higher affinity binding than is observed with the monomer in all cases
      tested. Since these dextran conjugates are simple to construct, they provide a
      general and convenient strategy to transform modest affinity antibody ligands
      into high affinity probes. An additional advantage is that the antibody ligands
      occupy only a small number of the reactive sites on the dextran, so that
      molecular cargo can be attached easily, creating molecules capable of delivering
      this cargo to cells displaying antigen-specific receptors. 

PMID- 25073656
TI  - Results of a prospective thyroid ultrasound screening program in adenomatous
      polyposis patients.
AB  - BACKGROUND: Patients with adenomatous polyposis may be at increased risk for
      developing thyroid cancer (TC). However, screening guidelines for TC in these
      patients are not well established. METHODS: Patients with a diagnosis of familial
      adenomatous polyposis, attenuated familial adenomatous polyposis, and gene
      mutation-negative adenomatous polyposis enrolled in our Hereditary Colorectal
      Cancer Family Registry were eligible for a screening thyroid ultrasound (US).
      Findings were reviewed by the study endocrinologist and intervention and/or
      follow-up determined. RESULTS: Fifty patients underwent screening thyroid US.
      Thirty-four (68%) patients had abnormal findings on US, including 27 (79%) with
      thyroid nodules. In 7 patients, US-detected thyroid nodules met established
      criteria for fine-needle aspiration. Of the 6 patients who underwent fine-needle
      aspiration, 2 (4%) were diagnosed with papillary TC. Both of these patients were
      female. CONCLUSIONS: A large proportion of adenomatous polyposis patients will
      have abnormal results on thyroid US, including suspicious-appearing thyroid
      nodules that when biopsied are malignant. Female patients have an apparently
      greater risk of developing TC. Polyposis patients, especially women, should be
      offered participation in a thyroid US screening program.

PMID- 25073657
TI  - Laparoscopic cyst fenestration in the treatment of polycystic liver disease.
AB  - INTRODUCTION: The PLD, included in the group of malformative lesions of ductal
      plate, is characterized by progressive development of multiple parenchymal cysts.
      Different surgical treatments have been proposed for symptomatic patients with
      PLD: percutaneus aspiration, fenestration, hepatic resection and liver
      transplantation. The aim of this report is to outline the treatment of polycystic
      liver disease with laparoscopic fenestration. MATERIALS AND METHODS: Of thirteen
      patients with PLD, in all cases associated with polycystic kidney disease, 7
      patients underwent to laparoscopic treatment of cysts fenestration, and 6,
      asymptomatic and not amenable to surgical treatment, underwent to clinical follow
      up. Of the 7 patients, 5 have symptoms related to "effect mass" 1-2-3 of hepatic
      cysts while in the 2 asymptomatics the fenestration of the cysts was performed
      during the procedure of laparoscopic cholecystectomy for cholelithiasis.
      DISCUSSION: The best indication for laparoscopic fenestration are those cases of
      PLD characterized by a relatively limited number of large cysts, preferably
      situated in the anterior segments of the liver and in the left lobe; in this
      patients, laparoscopic fenestration reduces significantly the volume of the liver
      and relieves symptoms. The laparoscopic fenestration of hepatic cyst, in
      carefully selected patients, is an effective technique in terms of morbidity,
      mortality, conversion rate and recurrence rates; while in patients with cyst
      diffuse in liver parenchyma is indicated the hepatic resection or liver
      transplantation. The optimal surgical approach is still evolving, the type of
      approach is related to extent and distribution of the cysts, and vascular anatomy
      of normal segment of the liver. KEY WORDS: Laparoscopic fenestration, Policystic
      liver.

PMID- 25073658
TI  - Species-specific and pathotype-specific binding of bacteria to zymogen granule
      membrane glycoprotein 2 (GP2).

PMID- 25073659
TI  - The experience of psychiatry training in rural NSW.
AB  - OBJECTIVE: To examine the experience of psychiatry training in rural New South
      Wales. METHOD: All rural trainees in New South Wales and key psychiatrists
      involved in their training were invited to complete a survey in May-July 2013.
      RESULTS: Responses were received from 26 out of 44 rurally placed psychiatry
      trainees (57% response rate) and 37 out of 55 psychiatrists involved in training
      in a rural area (67% response rate). Positive and negative aspects of rural
      training were reported. In general, trainees reported positive experiences
      regarding supervision, consultant input and their Site Coordinator of training.
      Their experience of other aspects of training and education in rural areas was
      often negative with 52% of trainees feeling at a disadvantage due to fewer
      registrar peers and 60% feeling educationally isolated. Difficulty progressing
      through training, workforce shortages, difficulty accessing formal aspects of
      training and limited options for advanced training were reported. Metropolitan
      trainees on rotation to rural terms receive accommodation, travel and an increase
      in wage from the rural Local Health District. Rural trainees on rotation to the
      city for their mandatory subspecialty training receive no such support.
      CONCLUSIONS: There are many challenges for rural trainees. Support from the Royal
      Australian and New Zealand College of Psychiatrists and state and federal
      governments to enhance the rural training experience is vital.

PMID- 25073660
TI  - Commentary.

PMID- 25073661
TI  - Predictive factors for a single successful cytapheresis session during the first
      mobilisation.
AB  - To avoid repeated apheresis, the objective of this study was to analyse the
      predictive factors for a single successful cytapheresis during the first
      mobilisation. The pre-collection characteristics of 170 lymphoma and 95 myeloma
      patients were analysed. Among 60 lymphoma patients who had less than 30 CD34
      cells/mm(3) the day before the first apheresis, an increase in the CD34 cell
      count between Day -1 and Day 1 was predictive of first stem cell mobilisation
      success, with a sensitivity of 100% if the Day 1 was higher than 30/mm(3) (10/60
      patients). Success rate of obtaining an appropriate number of stem cells in one
      apheresis was 120 among 170 patients. 

PMID- 25073662
TI  - Feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy in
      a short stay setting in patients with colorectal cancer at high risk of
      peritoneal carcinomatosis.
AB  - INTRODUCTION: Treatment of peritoneal carcinomatosis (PC) of colorectal cancer
      (CRC) origin is relatively ineffective and associated with morbidity. This raises
      the question whether we should focus on prevention of the development of PC. We
      determined the feasibility of adjuvant laparoscopic hyperthermic intraperitoneal
      chemotherapy (HIPEC) in a short stay setting. METHODS: A prospective single
      centre pilot study was conducted between January 2011 and July 2012. Ten patients
      at risk of developing PC of CRC origin were included. Laparoscopic HIPEC using
      Mitomycin-C (90 min; inflow temperature 42-43  degrees C) was performed within
      several weeks after primary resection of CRC and was considered feasible when
      postoperative hospital stay was three days or shorter in at least six patients,
      and if a maximum of one conversion and one re-admission within 30 days occurred.
      RESULTS: HIPEC was performed after a median of 6 weeks (range 3-9 weeks).
      Postoperatively, five patients were discharged at day one, four patients at day
      two and one patient at day three. Laparoscopic adhesiolysis resulted in small
      bowel injury in one patient, but no conversion to open surgery and no
      postoperative complications were observed. One patient was readmitted within 30
      days due to a clostridium infection. The postoperative course was uneventful for
      the remaining patients. CONCLUSION: Adjuvant laparoscopic HIPEC appeared to be
      feasible in a short stay setting based on this small pilot study. The necessity
      of adhesiolysis determines the complexity of the procedure and requires an
      operating team with experience in minimally invasive abdominal surgery.

PMID- 25073663
TI  - Single-use autoinjector for peginterferon-beta1a treatment of relapsing-remitting
      multiple sclerosis: safety, tolerability and patient evaluation data from the
      Phase IIIb ATTAIN study.
AB  - OBJECTIVES: A sub-study to evaluate safety, tolerability, ease-of-use and patient
      satisfaction with a single-use autoinjector administering subcutaneous
      peginterferon-beta1a (a pegylated interferon-beta1a in clinical development) in a
      subset of relapsing-remitting multiple sclerosis (MS) patients participating in
      ATTAIN, a long-term dose-frequency blinded extension of the Phase III randomized
      ADVANCE study. METHODS: Over 8 weeks, patients self-administered peginterferon
      beta1a 125 ug or placebo every 2 weeks (two injections via manual pre-filled
      syringe [PFS]; two injections via single-use autoinjector). Primary end points
      were incidence of adverse events (AEs), patient assessment of injection pain
      score (10-point Visual Analog Scale), and clinician assessment of injection site
      reactions (ISRs). Secondary objectives included patient assessment of ease-of-use
      and satisfaction with the autoinjector and evaluation of autoinjector training
      materials. RESULTS: In 39 patients, the safety profile of peginterferon-beta1a
      was similar when delivered via autoinjector or PFS; AEs were mostly mild or
      moderate in severity. Clinicians and patients reported a similar tolerability
      profile using both PFS and autoinjector, and pain scores were low (< 1), with no
      reports of clinician-assessed ISRs after administration with the autoinjector.
      Patients perceived the single-use autoinjector to be easy to use and convenient;
      overall patient satisfaction with the autoinjector and accompanying training
      materials was high. CONCLUSION: The safety and tolerability profile of
      peginterferon-beta1a delivered via autoinjector was similar to delivery via PFS.
      Patients found the autoinjector easy to use and convenient; this device may
      simplify the injection process for MS patients who require long-term therapy,
      thereby potentially improving patient's quality of life and adherence.

PMID- 25073664
TI  - Failure patterns after hemithoracic pleural intensity modulated radiation therapy
      for malignant pleural mesothelioma.
AB  - PURPOSE: We previously reported our technique for delivering intensity modulated
      radiation therapy (IMRT) to the entire pleura while attempting to spare the lung
      in patients with malignant pleural mesothelioma (MPM). Herein, we report a
      detailed pattern-of-failure analysis in patients with MPM who were unresectable
      or underwent pleurectomy/decortication (P/D), uniformly treated with hemithoracic
      pleural IMRT. METHODS AND MATERIALS: Sixty-seven patients with MPM were treated
      with definitive or adjuvant hemithoracic pleural IMRT between November 2004 and
      May 2013. Pretreatment imaging, treatment plans, and posttreatment imaging were
      retrospectively reviewed to determine failure location(s). Failures were
      categorized as in-field (within the 90% isodose line), marginal (<90% and >=50%
      isodose lines), out-of-field (outside the 50% isodose line), or distant. RESULTS:
      The median follow-up was 24 months from diagnosis and the median time to in-field
      local failure from the end of RT was 10 months. Forty-three in-field local
      failures (64%) were found with a 1- and 2-year actuarial failure rate of 56% and
      74%, respectively. For patients who underwent P/D versus those who received a
      partial pleurectomy or were deemed unresectable, the median time to in-field
      local failure was 14 months versus 6 months, respectively, with 1- and 2-year
      actuarial in-field local failure rates of 43% and 60% versus 66% and 83%,
      respectively (P=.03). There were 13 marginal failures (19%). Five of the marginal
      failures (38%) were located within the costomediastinal recess. Marginal failures
      decreased with increasing institutional experience (P=.04). Twenty-five patients
      (37%) had out-of-field failures. Distant failures occurred in 32 patients (48%).
      CONCLUSIONS: After hemithoracic pleural IMRT, local failure remains the dominant
      form of failure pattern. Patients treated with adjuvant hemithoracic pleural IMRT
      after P/D experience a significantly longer time to local and distant failure
      than patients treated with definitive pleural IMRT. Increasing experience and
      improvement in target delineation minimize the incidence of avoidable marginal
      failures.

PMID- 25073665
TI  - [Belching (eructation)].
AB  - Belching is a normal physiological function that may occur when ingested air
      accumulated in the stomach is expelled or when food containing air and gas
      produced in the gastrointestinal tract is expelled. Excessive belching can cause
      patients to complain of abdominal discomfort, disturbed daily life activities,
      decreased quality of life and may be related to various gastrointestinal
      disorders such as gastroesophageal reflux disease, functional dyspepsia,
      aerophagia and rumination syndrome. Belching disorders can be classified into
      aerophagia and unspecified belching disorder according to the Rome III criteria.
      Since the introduction of multichannel intraluminal impedance monitoring, efforts
      are being made to elucidate the types and pathogenic mechanisms of belching
      disorders. Treatment modalities such as behavioral therapy, speech therapy,
      baclofen, tranquilizers and proton pump inhibitors can be attempted, but further
      investigations on the effective treatment of belching disorders are warranted.

PMID- 25073666
TI  - [Proteomics analysis for Helicobacter pylori-infected gastric mucosa].
AB  - BACKGROUND/AIMS: Helicobacter pylori infection is linked to the development of
      gastric cancer. H. pylori-associated gastric inflammation is considered to be the
      first important step in the histogenesis of such neoplasia. However, studies that
      compare proteome of gastric mucosa infected with or without H. pylori are
      lacking. METHODS: We employed proteomics analysis on the endoscopic biopsy
      specimens of gastric mucosa obtained from two groups (30 cases): healthy subjects
      without H. pylori infection (15 cases), and gastritis patients with H. pylori
      infection (15 cases). The pooled proteins obtained from gastric mucosa infected
      with or without H. pylori were separated by two-dimensional gel electrophoresis
      and analyzed by a computer-aided program. The altered protein expressions were
      then identified by mass spectrometry and validated by Western blotting and
      immunohistochemistry. RESULTS: On mass spectrometry using MALDI TOFTM Analyzer,
      the up-regulation of Keratin 1, ezrin, adenosine triphosphate (ATP) synthase
      subunit alpha mitochondrial isoform c, Keratin type I cytoskeletal 19, and
      Keratin type I cytoskeletal 9 were identified; in contrast, 71 kd heat shock
      cognate protein, ATP synthase subunit alpha mitochondrial precursor, and annexin
      IV were down-regulated. Among them, membrane cytoskeleton linker ezrin was
      validated using Western blot and immunohistochemistry. CONCLUSIONS: Expression of
      ezrin was significantly different between the gastric mucosa with and without H.
      pylori infection. Therefore, ezrin could be considered a promising potential
      molecular marker for detecting H. pylori infection in gastric mucosa.

PMID- 25073667
TI  - [Correlation between adenoma detection rate and advanced adenoma detection rate].
AB  - BACKGROUND/AIMS: Adenoma detection rate (ADR) is widely used as an index of
      colonoscopy quality management. Although advanced adenomas can be found less
      frequently than non-advanced adenomas, advanced adenomas have a higher clinical
      significance during screening for colorectal cancer. The aim of this study was to
      investigate the correlation between advanced and non-advanced ADR among
      colonoscopists. METHODS: This study is an observational study of a cohort of
      patients undergoing screening colonoscopy between 2009 and 2010. We collected the
      data on patients' characteristics and colonoscopic findings. The detection rates
      of adenoma and advanced adenoma were calculated. Logistic regression was used to
      determine the effects of variables on advanced adenoma detection, and spearman's
      rank-order correlation was used to evaluate the relationship between advanced ADR
      and ADR. RESULTS: A total of 561 patients underwent screening colonoscopy by 18
      experienced colonoscopists. Most colonoscopists had adequate (>20%) ADRs.
      Logistic regression showed that increased patient age (OR 1.07 per 1 year
      increase, 95% CI 1.009-1.133, p=0.023) and male gender (OR 1.860, 95% CI 0.764
      4.529, p=0.171) were associated with advanced ADR. When colonoscopists were
      divided into two groups on the basis of advanced ADR of 5%, ADR was also
      significantly higher in the group having higher level of advanced ADR. However,
      there was no correlation between advanced ADR and ADR among colonoscopists as an
      individual. CONCLUSIONS: Colonoscopists' advanced ADRs were independent of their
      ADRs, indicating that advanced ADR could be quite low even among colonoscopists
      with acceptable ADRs. Thus, there seems to be a limitation in using ADR as an
      adequate index of colonoscopy quality management.

PMID- 25073668
TI  - [Factors influencing the miss rate of polyps in a tandem colonoscopy study].
AB  - BACKGROUND/AIMS: The miss rate of colon polyps and its related factors have not
      been clearly identified yet. This study aims to review the miss rate of polyps
      both on the patient-level and on the polyp-level and to analyze the factors
      affecting the miss rate such as those related to the endoscopist, procedure,
      patient, and polyp. METHODS: From August 2011 to August 2013, patients who
      underwent elective second colonoscopy for resection of polyps, the sizes of which
      were not small enough to be resected by biopsy forceps alone at first
      colonoscopy, were enrolled retrospectively. RESULTS: The miss rate on the patient
      level was 59.2% (234/395) and on the polyp-level was 27.9% (578/2,068). There was
      no significant difference in the miss rate depending on the experience of the
      endoscopists or characteristics of the patients. In terms of the procedure, the
      miss rate was higher when the colonoscopy was performed in the afternoon (OR
      1.632, p=0.046). It was found that the miss rate of polyps increased when the
      polyps were small (OR 4.595, p<0.001 in <5 mm/OR 3.447, p<0.001 in 5-10 mm), flat
      or sessile (OR 2.406, p<0.001 in flat/OR 1.768, p=0.002 in sessile), and located
      in the left colon (OR 1.391, p=0.007). CONCLUSIONS: The experience of
      endoscopists did not have influence on the accuracy of polyp detection. However,
      the fatigue of endoscopists in the afternoon is considered to render polyp
      detection less accurate. Also, the large curves and folds of the sigmoid colon
      are regarded as a reason for the higher miss rate of polyps in the left colon.

PMID- 25073669
TI  - [Comparison on the efficacy and safety of biphenyl dimethyl dicarboxylate and
      ursodeoxycholic acid in patients with abnormal alanine aminotransferase:
      multicenter, double-blinded, randomized, active-controlled clinical trial].
AB  - BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic
      fibrosis and fatal complication in most liver diseases. The aim of this study is
      to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and
      ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred
      thirty-five patients with elevated ALT were randomized to receive either 750
      mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety
      three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic
      hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate
      of ALT normalization at week 24. The secondary endpoints were changes in AST,
      liver stiffness, and the incidence of adverse events. RESULTS: A total of 101
      patients completed 24 weeks of therapy. ALT normalization at week 24 was observed
      in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001).
      Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB
      group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST
      level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly
      different between the two groups. Severe adverse drug reaction occurred in 1
      patient in DDB group but the subject continued therapy during the study period.
      CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore
      it was safe and well tolerated by patients with abnormal ALT.

PMID- 25073670
TI  - A case of recurrent abdominal pain with fever and urticarial eruption.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurrent episodes of fever and serosal, synovial, or cutaneous
      inflammation, caused by a dysfunction of pyrin as a result of mutation within the
      MEFV gene. It occurs mainly among Mediterranean and Middle Eastern populations,
      including Jews, Arabs, and Turks. However, FMF cases have been reported outside
      the Mediterranean and Middle Eastern countries in recent years. Although FMF has
      been relatively rare in Korea until now, proper recognition of FMF might lead to
      more frequent diagnoses of FMF. We experienced an interesting case, a 31-year-old
      Korean man who presented with recurrent abdominal pain with fever and urticarial
      eruption for 10 years. DNA analysis showed complex mutations (p.Leu110Pro,
      p.Glu148Gln) in the MEFV gene. To date, three cases have been reported, and this
      case of FMF with skin conditions is the first case in Korea.

PMID- 25073671
TI  - Colonic abscess induced by India ink tattooing.
AB  - Endoscopic tattooing with India ink is generally regarded as a safe procedure
      that enables ready identification of endoluminal cancer from the serosal surface.
      However, significant complications have been reported, including local
      inflammatory pseudotumor formation, peritonitis, rectus muscle abscess, small
      bowel infarction, and phlegmonous gastritis. Although the mechanism of
      complication is not completely understood, it may be related to the chemical
      compounds contained in the ink solution and enteric or extraenteric bacterial
      inoculation by injection needle or the ink itself. Authors encountered a case of
      a 60-year-old man with a resectable sigmoid colon cancer which was tattooed with
      India ink for subsequent localization in the intraoperative setting. During the
      laparoscopic operation, the proximal and distal margin of the lesion appeared
      edematous with bluish color. The distal resection margin was extended
      approximately 5 cm more than expected because of long extent of edematous mucosa.
      Histologic examination of the edematous tattooing area revealed an ink abscess
      spreading laterally above the muscularis propria. Although tattooing is widely
      used and relatively safe, the presented case indicates the risk of infection or
      inflammation by tattooing.

PMID- 25073672
TI  - [Recurrence of multiple focal nodular hyperplasia in a young male patient].
AB  - Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor
      that is usually found in women. Diagnosis of FNH mainly depends on imaging
      studies such as color Doppler flow imaging, computed tomography, and magnetic
      resonance imaging. It is characterized by the presence of stellate central scar
      and is nowadays incidentally diagnosed with increasing frequency due to advances
      in radiologic imaging technique. FNH typically presents as a single lesion in 70%
      of cases and generally does not progress to malignancy or recur after resection.
      Herein, we report a case of a young male patient with recurrent multiple FNH who
      underwent surgical resection for presumed hepatic adenoma on computed tomography.

PMID- 25073673
TI  - Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a
      case report with a literature review.
AB  - Aloe is one of the leading products used in phytomedicine. Several cases of aloe
      induced toxic hepatitis have been reported in recent years. However, its
      toxicology has not yet been systematically described in the literature. A 21-year
      old female patient was admitted to our hospital with acute hepatitis after taking
      an aloe vera preparation for four weeks. Her history, clinical manifestation,
      laboratory findings, and histological findings all led to the diagnosis of aloe
      vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis
      induced by aloe vera.

PMID- 25073675
TI  - TIR-domain-containing adapter-inducing interferon-beta (TRIF) regulates Th17
      mediated intestinal immunopathology in colitis.
AB  - Gastrointestinal mucosa reserves abundant Th17 cells where host response to
      commensal bacteria maintains Th17-cell generation. Although functional
      heterogeneity and dynamic plasticity of Th17 cells appear to be involved in
      chronic inflammatory disorders, how their plasticity is regulated in intestinal
      mucosa is unknown. Here we show that innate TRIF signaling regulates intestinal
      Th17-cell generation and plasticity during colitis. Absence of TRIF in mice
      resulted in increased severity of experimental colitis, which was associated with
      aberrant generation of Th17 cells especially of interferon (IFN)-gamma-expressing
      Th17 cells in the lamina propria. The abnormal generation and plasticity of Th17
      cells involved impaired expression of interleukin (IL)-27p28 by lamina propria
      macrophages but not dendritic cells. Treatment of TRIF-deficient mice with IL
      27p28 during colitis reduced the number and IFN-gamma expression of Th17 cells in
      the intestine. In vitro, TRIF-deficient macrophages induced more Th17 cells than
      wild-type (WT) macrophages during co-culture with WT naive T cells in response to
      cecal bacterial antigen. Many of Th17 cells induced by TRIF-deficient macrophages
      expressed IFN-gamma due to impaired expression of IL-27p28 by macrophages and
      defective activation of STAT1 in T cells. These results outline TRIF-dependent
      regulatory mechanism by which host response to intestinal bacteria maintains Th17
      cell-mediated pathology during colitis. 

PMID- 25073678
TI  - Evaluation of a closed-system cytotoxic transfer device in a pharmaceutical
      isolator.
AB  - PURPOSE: The occupational risk associated with handling of cytotoxic anticancer
      drugs is well documented and, in many countries, pharmaceutical isolators are
      used to contain cytotoxic residues during preparation of cytotoxic infusions.
      Isolators are difficult to clean leading to concerns that cytotoxic contamination
      from the work area could be transferred to surfaces of products leaving the
      isolator. This study investigated the surface contamination arising from the
      preparation of five anticancer drug infusions (Epirubicin, Fluorouracil,
      Cisplatin, Oxaliplatin and Carboplatin) in a pharmaceutical isolator and compared
      use of a conventional syringe and needle technique with a closed-system drug
      transfer device (CSDTD). METHODS: Wipe samples were taken over 1 week from pre
      defined areas in the isolator, gloves, preparation mats, and also from the
      surfaces of prepared cytotoxic infusion bags and pre-filled syringes to obtain
      baseline surface contamination data. Following operator familiarisation, the
      CSDTD was then introduced and sampling repeated for a further week (intervention
      period). The samples obtained were analysed using validated HPLC-UV, HPLC-FL and
      ICP-MS techniques, as appropriate. RESULTS: All surfaces sampled during baseline,
      including external surfaces of infusions and syringes, were contaminated with
      each marker drug. During the intervention phase, isolator surfaces were free from
      detectable contamination and the contamination measured on gloves, preparation
      mats and surface of infusions was markedly reduced. The frequency of
      contamination on syringe and infusion surfaces was also lower. CONCLUSION:
      Surface contamination from cytotoxic infusion preparation in a pharmaceutical
      isolator was significant and could transmit cytotoxic residues to patient and
      public areas via infusion surfaces. The frequency and amount of contamination
      were reduced by the CSDTD.

PMID- 25073679
TI  - [Endoscopic treatment of giant duodenal lipoma].

PMID- 25073677
TI  - Interferon-gamma-producing B cells induce the formation of gastric lymphoid
      follicles after Helicobacter suis infection.
AB  - Helicobacter (H.) suis is capable of infecting various animals including humans,
      and H. suis infections can lead to gastric mucosa-associated lymphoid tissue
      (MALT) lymphoma. Recently, we reported that interferon-gamma (IFN-gamma) was
      highly expressed in the stomachs of H. suis-infected mice, but the direct
      relationship between the upregulation of IFN-gamma expression and the formation
      of gastric lymphoid follicles after H. suis infection remains unclear. Here, we
      demonstrated that the IFN-gamma produced by B cells plays an important role in
      the formation of gastric lymphoid follicles after H. suis infection. In addition,
      IFN-gamma-producing B cells evoked gastric lymphoid follicle formation
      independent of T-cell help, suggesting that they are crucial for the development
      of gastric MALT induced by Helicobacter infection. 

PMID- 25073680
TI  - [Toxic hepatocellular hepatitis due to labetalol].

PMID- 25073676
TI  - Classical versus alternative macrophage activation: the Ying and the Yang in host
      defense against pulmonary fungal infections.
AB  - Macrophages are innate immune cells that possess unique abilities to polarize
      toward different phenotypes. Classically activated macrophages are known to have
      major roles in host defense against various microbial pathogens, including fungi,
      while alternatively activated macrophages are instrumental in immune-regulation
      and wound healing. Macrophages in the lungs are often the first responders to
      pulmonary fungal pathogens, and the macrophage polarization state has the
      potential to be a deciding factor in disease progression or resolution. This
      review discusses the distinct macrophage polarization states and their roles
      during pulmonary fungal infection. We focus primarily on Cryptococcus neoformans
      and Pneumocystis model systems as disease resolution of these two opportunistic
      fungal pathogens is linked to classically or alternatively activated macrophages,
      respectively. Further research considering macrophage polarization states that
      result in anti-fungal activity has the potential to provide a novel approach for
      the treatment of fungal infections. 

PMID- 25073681
TI  - Mediterranean spotted fever in a patient with Crohn's disease under adalimumab:
      First case report and review of the literature.

PMID- 25073682
TI  - Supraglottoplasty outcomes in neurologically affected and syndromic children.
AB  - IMPORTANCE: Supraglottoplasty (SGP) failure is frequently attributed to
      coexistent medical comorbidities, but studies specifically evaluating outcomes in
      these populations are lacking. OBJECTIVE: To assess SGP outcomes in patients with
      neurologic and syndromic comorbidities and severe laryngomalacia (LM). DESIGN,
      SETTING, AND PARTICIPANTS: Case series with retrospective review of medical
      records of 54 patients with neurologic and/or syndromic comorbidity and severe LM
      who underwent SGP between 2004 and 2012 at a tertiary care pediatric institution.
      INTERVENTIONS: Patients presented with severe LM that required SGP.
      Supraglottoplasty failure necessitated revision SGP, tracheostomy, or gastrostomy
      tube insertion, or LM and obstructive sleep apnea that required assisted
      ventilation (continuous positive airway pressure and bilevel positive airway
      pressure). MAIN OUTCOMES AND MEASURES: Medical records were reviewed with a focus
      on patient factors, surgical timing, complications, and surgical and dysphagia
      outcomes. Patients were grouped based on their age at the time of SGP as infants
      (aged <=12 months) and children (aged >12 months). Statistical comparisons were
      performed with SGP outcomes of infants with LM and no comorbidities. RESULTS:
      Fifty-four patients met the inclusion criteria. Thirty-one (13 infants, 18
      children) had a neurologic condition and 23 (15 infants, 8 children) had
      syndromes. The overall success rate of SGP was 67% (36 of 54) in these
      populations. Neurologic (P = .003) and syndromic (P < .001) comorbidities were
      associated with significant reduction in SGP success rates vs no comorbidities.
      Among SGP failures (18 of 54 [33%]), 13% (7 of 54) required tracheostomy, 9% (5
      of 54) needed assisted ventilation, 7% (4 of 54) required a postoperative
      gastrostomy tube, and 4% (2 of 54) required revision SGP. In the neurologic
      comorbidities group, patients with cerebral palsy had significantly higher
      tracheostomy rates compared with those who had other neurologic pathologies
      constituting comorbidities (2 of 11 [18%] vs 0 of 20; P = .049). In infants,
      acute airway obstruction was the most common indication for SGP in the
      neurologically comorbidity and syndrome populations (success rates, 69% and 67%,
      respectively). In children, obstructive sleep apnea was the most common
      indication for SGP in the neurologic comorbidity and syndrome populations
      (success rates, 78% and 50%, respectively). CONCLUSIONS AND RELEVANCE:
      Supraglottoplasty remains useful and outcomes were better in patients with
      neurologic comorbidity than in patients with syndromic comorbidity.

PMID- 25073683
TI  - Refined bleeding estimates in adults starting anticoagulants.

PMID- 25073684
TI  - Autotrophic denitrification performance and bacterial community at biocathodes of
      bioelectrochemical systems with either abiotic or biotic anodes.
AB  - Two-chamber bioelectrochemical systems (BESs) have recently been developed for
      nitrate removal from nitrate-contaminated water. In this study, we compared the
      nitrate removal performance of biocathodes of BESs when using abiotic and biotic
      anodes. Acetate was used as electron donor in BESs with biotic anode, whereas a
      direct current power supply was used as energy source in BESs with abiotic anode.
      The nitrogen removal efficiency increased from 18.1% to 43.0% when the voltage
      supplied to the BES with abiotic anode increased from 0.7 V to 0.9 V, whereas no
      higher removal efficiency was obtained at a higher supplied voltage (1.1 V). The
      highest efficiency (78.0%) of autotrophic nitrogen removal was achieved when
      electron transfer from the biotic anode chamber of BESs was used. Unexpectedly,
      control of the cathode potential did not enhance nitrate removal in BESs with
      biotic anode. Special attention was paid to elucidate the differences of
      bacterial communities catalysing autotrophic denitrification in the biocathodes
      of BESs with abiotic and biotic anodes. Data from denaturing gradient gel
      electrophoresis and phylogenetic analysis suggested that denitrification in BESs
      with abiotic anode could be attributed to Nitratireductor sp., Shinella sp., and
      Dyella sp., whereas the dominant bacterial denitrifiers in BESs with biotic anode
      were found to be Pseudomonas sp., Curtobacterium sp., and Aeromonas sp. These
      results implied that biocathodes of BESs with biotic anode are more efficient
      than those of BESs with abiotic anode for nitrate removal from nitrate
      contaminated water in practical applications. 

PMID- 25073685
TI  - Expression of key hydrolases for soy sauce fermentation in Zygosaccharomyces
      rouxii.
AB  - Several key hydrolases in soy sauce fermentation such as proteases, peptidases,
      and glutaminases are supplied by Aspergillus sojae or Aspergillus oryzae. The
      genes encoding these hydrolases were successfully expressed in salt-tolerant
      yeast Zygosaccharomyces rouxii. These transformants are expected to supply extra
      hydrolases during soy sauce fermentation process. 

PMID- 25073686
TI  - Surgical sequence of reduction in double mandibular fractures treatment.
AB  - AIM: This study aims to clarify, according to our experience, the correct
      surgical sequence which should be followed in order to treat double mandibular
      fractures. MATERIAL OF STUDY: From January 2007 to January 2010, we have
      conducted a retrospective study on a sample of patients operated on in our
      department. We include only those cases in which the jaw was fractured in 2
      places, in particular patients who suffer a fracture in tooth-bearing areas
      (symphysis, parasymphysis, and anterior body) and also contralaterally in non
      tooth-bearing areas (posterior body, angle, ramus, and condyle). The sample was
      divided into 2 groups based on the fracture sequence of reduction. RESULTS: At 1
      year follow-up, the group of patients who received first the tooth-bearing
      fractured areas treatment, followed by treatment of non tooth-bearing fractured
      area on bifocal mandibular fracture (Group A), showed less postoperative
      complications and reduced surgical time and costs. DISCUSSION: In patients of
      group B, the non-execution of rigid IMF for the non tooth-bearing fractures made
      bone segments more free to move. Thus, reduction and fixation of non tooth
      bearing fractures is facilitated, but poses a greater risk of complications. The
      surgeon in this case does not have the occlusal help guide; thus, the tooth
      bearing fracture reduction and the subsequent fixation may be imperfect.
      CONCLUSION: It is recommended from this study that reduction of the tooth-bearing
      fragment be prior to that of the tooth-free fragment for the double mandibular
      fracture. KEY WORDS: Double mandibular fractures, Toothbearing area, Multiple
      mandibular fracture, Non-toothbearing area.

PMID- 25073687
TI  - Functionalized graphitic carbon nitride for metal-free, flexible and rewritable
      nonvolatile memory device via direct laser-writing.
AB  - Graphitic carbon nitride nanosheet (g-C3N4-NS) has layered structure similar with
      graphene nanosheet and presents unusual physicochemical properties due to the s
      triazine fragments. But their electronic and electrochemical applications are
      limited by the relatively poor conductivity. The current work provides the first
      example that atomically thick g-C3N4-NSs are the ideal candidate as the active
      insulator layer with tunable conductivity for achieving the high performance
      memory devices with electrical bistability. Unlike in conventional memory diodes,
      the g-C3N4-NSs based devices combined with graphene layer electrodes are
      flexible, metal-free and low cost. The functionalized g-C3N4-NSs exhibit
      desirable dispersibility and dielectricity which support the all-solution
      fabrication and high performance of the memory diodes. Moreover, the flexible
      memory diodes are conveniently fabricated through the fast laser writing process
      on graphene oxide/g-C3N4-NSs/graphene oxide thin film. The obtained devices not
      only have the nonvolatile electrical bistability with great retention and
      endurance, but also show the rewritable memory effect with a reliable ON/OFF
      ratio of up to 10(5), which is the highest among all the metal-free flexible
      memory diodes reported so far, and even higher than those of metal-containing
      devices. 

PMID- 25073689
TI  - Sudden loss of consciousness during a flight.

PMID- 25073688
TI  - Glutamate metabolism in major depressive disorder.
AB  - Research on novel treatments for major depressive disorder focuses quite deeply
      on glutamate function, and this research would benefit from a brain-imaging
      technique that precisely quantified glutamate function. Signs of a specific form
      of glutamate-related dysfunction that could be targeted by novel therapies were
      found using novel, state-of-the-art techniques to address this issue. 

PMID- 25073690
TI  - Non-traditional factors in childhood obesity: the Italy-India joint research
      programme 2012-2014.

PMID- 25073691
TI  - Epilepsy, cognition and behavior.
AB  - Epilepsy is defined as two or more unprovoked seizures. Epileptic patients have
      intellectual disability and behavioral co-morbidities to the tune of up to 25 and
      75% respectively. Various factors like underlying etiology, socioeconomic
      environment at home, age at onset, seizure semiology, seizure descriptors like
      duration, severity and frequency, therapy related adverse effects secondary to
      antiepileptic drugs and epilepsy surgery have been implicated for the causation
      of cognitive and behavioral impairment in epilepsy. Cognitive epilepsy has
      emerged as a specific entity. This may manifest as a transient behavioral or
      cognitive change, insidous onset subacute to chronic encephalopathy or more
      catastrophic in the form of nonconvulsive status epilepticus. Cognitive
      impairment seen in epileptic children include difficulties in learning, memory,
      problem solving as well as concept formation. Anxiety, depression and attention
      deficit hyperkinetic disorders are the most common psychiatric co-morbidities
      seen. Investigating a child with epilepsy for cognitive and behavioral impairment
      is difficult as these tests would require cooperation from the patient's side to
      a significant extent. A rational approach towards treatment would be judicious
      selection of antiepileptic drugs, treatment of underlying cause, appropriate
      management of behavioral co-morbidities including psychopharmacotherapy and a
      trial of immunotherapy (particularly in cognitive epilepsies), wherever
      appropriate. 

PMID- 25073692
TI  - Zinc oxide quantum dots: a potential candidate to detain liver cancer cells.
AB  - The term cancer is used for diseases in which abnormal cells proliferate without
      control and are able to attack with other tissues. Over various types of cancers,
      liver cancer is the most hurtful disease, which affects the whole body system.
      The aim of the present study was to investigate the efficiency against cancer
      cells of HepG2 cells, with quantum dots of ZnO. The cytotoxic effects were
      analyzed with MTT assays in range of 1-100 MUg/ml. The cells were exposed to ZnO
      QDs and it exhibit significant reduction, which starts from concentration 5
      MUg/ml (4 %; p < 0.05). The assay was justified with quantitative RT-PCR and it
      demonstrates, exposure of ZnO-QDs on HepG2 cells. The level of mRNA expressions
      was significantly up-regulated (Bax, P53, and Caspase-3), whereas the anti
      apoptotic gene (Bcl-2) was down-regulated. The QDs (5 +/- 2 nm) were prepared via
      soft chemical solution process and analyzed using FESEM, TEM and HR-TEM.

PMID- 25073693
TI  - Seasonal variations in toxic metal levels of two fish species, Mugil cephalus and
      Mullus barbatus and estimation of risk for children.
AB  - Concentrations of five toxic metals were determined in two fish species namely,
      Mugil cephalus and Mullus barbatus consumed in two neighboring Turkish cities
      during 2010-2011. Lead concentrations (mean 900 MUg kg(-1)) for M. cephalus were
      found to be higher than the maximum allowances concentration (MAC) of 300 MUg kg(
      1). Similarly, Cr (mean 410 MUg kg(-1)), Ni (mean 331 MUg kg(-1)) and Cu (mean
      834 MUg kg(-1)) concentrations in M. cephalus were significantly higher than in
      M. barbatus (mean 341 MUg Cr kg(-1), 256 MUg Ni kg(-1) and 568 MUg Cu kg(-1)).
      Although concentrations of some metals exceed the limits set by the authorities,
      the estimated non-carcinogenic and carcinogenic health risks by the Target Hazard
      Quotient and target carcinogenic risk indicate that there is no carcinogenic risk
      for humans, and the risk of developing cancer over a human lifetime is between 2
      and 12 in 1,000,000.

PMID- 25073694
TI  - Use of text-message reminders to improve participation in a population-based
      breast cancer screening program.
AB  - To analyze the effect of a cell text message reminder service on participation in
      a mammogram screening program in Catalonia, Spain. A quasi-experimental design
      was used with women aged 50 to 69 years who had been scheduled mammogram
      appointments in June or July 2011. Women were personally invited by letter to
      attend to the breast cancer screening program (n = 12,786). Prior to the
      invitation, 3,719 (29.1 %) of them had provided their cell telephone number to
      the National Health Service. These women received a text message reminder 3 days
      before their scheduled appointment. Logistic regression models were used to
      analyze whether the text message reminder was associated with participation in
      screening. Cost-effectiveness of adding a text message reminder to the invitation
      letter was also analyzed. The overall rate of participation in breast cancer
      screening was 68.4 %. The participation rate was significantly higher in the text
      messaging group, with an age-adjusted OR of 1.56 (95 %CI: 1.43-1.70). A detailed
      analysis showed that the increase in participation related to the text message
      reminder was higher among women without previous screening who lived in areas
      where access to postal mail was limited (OR=2.85; 95 %CI: 2.31-3.53) compared to
      those who lived in areas of easier postal mail access (OR=1.66; 95 %CI: 1.36
      2.02). The invitation letter+text message reminder was a cost-effective strategy.
      Text message reminders are an efficient cost-effective approach to improve
      participation in difficult-to-reach populations, such as rural areas and newly
      developed suburbs.

PMID- 25073695
TI  - Bicomponent hydrogen-bonded nanostructures formed by two complementary molecular
      Landers on Au(111).
AB  - The co-adsorption of two molecular Landers equipped with functional groups
      capable of forming a complementary triple hydrogen-bonding motif is investigated
      with scanning tunneling microscopy and molecular mechanics calculations.
      Surprisingly, the anticipated complementary motif is not realised in 2-D terrace
      structures, but is observed in 1-D structures at step edges where molecular
      conformational flexibility is confined. 

PMID- 25073696
TI  - Local ELF-magnetic field: a possible novel therapeutic approach to psychology
      symptoms.
AB  - The recorded EEG of some brain regions of patients such as attention deficit
      hyperactivity disorder (ADHD), depression and etc. are different in comparison to
      healthy people. The disease improves with modifying the patient EEG that this is
      the basis of neurofeedback training. The main disadvantage of neurofeedback
      training demands patient's collaborative and active participation during
      treatment sessions, while some of patients such as addicts, depressed people and
      ADHD children cannot easily concentrate in direction of therapist's purpose.
      Furthermore, extremely low frequency magnetic fields (MFs) can affect brain
      signals and change them that in some cases lead to clinical effects. This report
      proposes if by locating small coils in desired region proceeds to local exposure
      of brain and happens in different frequencies or intensities and the effects of
      each MF in brain signals get analyzed then by knowing its effects we can make
      changes in patient voluntary without direct participation of patient in his/her
      brain signal changes. In the other words by changing type of the MF exposure and
      immediate record of brain signals we can fallow brain signals by observing the
      immediate record after exposure, with changes in the amplitude and the next
      exposure frequency, the therapist tries to direct the brain signal of desired
      region to the purpose. The possibility of approving this hypothesis in spite of
      contradictory effects about recovery or appearance of depression because of the
      MF and ability of local magnetic field exposures in changing of brain signals get
      reinforced to some extent. 

PMID- 25073697
TI  - SUNCT-like syndrome attributed to varicella-zoster virus meningoencephalitis.

PMID- 25073698
TI  - Time-effect relationship of extracts from ginseng, notoginseng and chuanxiong on
      vascular endothelial cells senescence.
AB  - OBJECTIVE: To observe the time-effect relation of extracts from ginseng,
      notoginseng and chuanxiong on angiotensin II (Ang II)-induced senescence of
      vascular endothelial cells and explore the feature of Chinese medicine against
      vascular diseases. METHODS: Human umbilical vein endothelial cells (HUVECs)
      cultured in vitro were stimulated with 10(-6) mol/L AngII to induce cell
      senescence, which were divided into 4 groups, the blank control group, the Ang II
      model group, the extracts group and the telmisartan group. The beta-gal was used
      to identify senescence of cells, the cell counting kit-8 method was applied to
      assess the cell viability, the cell function was examined with the level of
      endothelial nitric oxide synthase (eNOS) and the flow cytometry was used for
      analyzing the cell cycle changes. RESULTS: Compared with the control cells, the
      cells positive for beta-gal staining was significantly increased in the Ang II
      model group, and showed cell cycle arrest at G0/G1 phase with decreased S and
      G2/M phase cell percentage, eNOS expression and cell viability (P<0.05). The
      extracts and telmisartan treatment of Ang II-induced cells resulted in decreased
      beta-gal positive cells with a reduction in G0/G1 phase cells and an increasing
      in S, G2/M phase cells and eNOS expression (P<0.05). At 24 h, the extracts were
      more effective than telmisartan (P<0.05); while telmisartan was more effective at
      48 h (P<0.05). CONCLUSION: Extracts from ginseng, notoginseng and chuanxiong can
      delay Ang II-induced aging of HUVECs and may play an important role in early
      senescence.

PMID- 25073699
TI  - Pharmacological treatment of diabetes in older people.
AB  - The pharmacological management of diabetes in older people is complex and
      challenging. It requires a comprehensive understanding of the individual beyond
      the diabetes itself. Through the ageing years, the older individual presents with
      diabetes-related and non-related comorbidities and complications, develops
      functional limitations and psychological issues, and may lack social support and
      access to care. A disturbance in these categories, known as the four geriatric
      domains, will negatively affect diabetes self-management and self-efficacy,
      leading to poor outcomes and complications. Furthermore, older people with
      diabetes may be more interested in the management of other chronic conditions
      such as pain or impaired mobility, and diabetes may be lower in their list of
      priorities. Proper education must be provided to the older individual and
      caregivers, with continuous monitoring and counselling, especially when
      pharmacological interventions offer risks of side effects, adverse reactions and
      interactions with other medications. Informed shared medical decisions will help
      to improve adherence to the regimen; however, such discussions ought to be based
      on the best evidence available, which is unfortunately limited in this age group.
      We performed a review focused on pharmacological agents and summarize current
      evidence on their use for the treatment of diabetes in older people. We encourage
      clinicians to investigate and incorporate the four geriatrics domains in the
      selection and monitoring of these agents.

PMID- 25073700
TI  - A new, objective, quantitative scale for measuring local skin responses following
      topical actinic keratosis therapy with ingenol mebutate.
AB  - INTRODUCTION: Local skin responses (LSRs) are the most common adverse effects of
      topical actinic keratosis (AK) therapy. There is currently no method available
      that allows objective characterization of LSRs. Here, the authors describe a new
      scale developed to quantitatively and objectively assess the six most common LSRs
      resulting from topical AK therapy with ingenol mebutate. METHODS: The LSR grading
      scale was developed using a 0-4 numerical rating, with clinical descriptors and
      representative photographic images for each rating. Good inter-observer grading
      concordance was demonstrated in peer review during development of the tool. Data
      on the use of the scale are described from four phase III double-blind studies of
      ingenol mebutate (n = 1,005). RESULTS: LSRs peaked on days 4 (face/scalp) or 8
      (trunk/extremities), with mean maximum composite LSR scores of 9.1 and 6.8,
      respectively, and a rapid return toward baseline by day 15 in most cases. Mean
      composite LSR score at day 57 was generally lower than at baseline. CONCLUSION:
      The LSR grading scale is an objective tool allowing practicing dermatologists to
      characterize and compare LSRs to existing and, potentially, future AK therapies.

PMID- 25073701
TI  - Quantitative proteomic analysis reveals posttranslational responses to aneuploidy
      in yeast.
AB  - Aneuploidy causes severe developmental defects and is a near universal feature of
      tumor cells. Despite its profound effects, the cellular processes affected by
      aneuploidy are not well characterized. Here, we examined the consequences of
      aneuploidy on the proteome of aneuploid budding yeast strains. We show that
      although protein levels largely scale with gene copy number, subunits of multi
      protein complexes are notable exceptions. Posttranslational mechanisms attenuate
      their expression when their encoding genes are in excess. Our proteomic analyses
      further revealed a novel aneuploidy-associated protein expression signature
      characteristic of altered metabolism and redox homeostasis. Indeed aneuploid
      cells harbor increased levels of reactive oxygen species (ROS). Interestingly,
      increased protein turnover attenuates ROS levels and this novel aneuploidy
      associated signature and improves the fitness of most aneuploid strains. Our
      results show that aneuploidy causes alterations in metabolism and redox
      homeostasis. Cells respond to these alterations through both transcriptional and
      posttranscriptional mechanisms.

PMID- 25073702
TI  - Serum amyloid A is a retinol binding protein that transports retinol during
      bacterial infection.
AB  - Retinol plays a vital role in the immune response to infection, yet proteins that
      mediate retinol transport during infection have not been identified. Serum
      amyloid A (SAA) proteins are strongly induced in the liver by systemic infection
      and in the intestine by bacterial colonization, but their exact functions remain
      unclear. Here we show that mouse and human SAAs are retinol binding proteins.
      Mouse and human SAAs bound retinol with nanomolar affinity, were associated with
      retinol in vivo, and limited the bacterial burden in tissues after acute
      infection. We determined the crystal structure of mouse SAA3 at a resolution of 2
      A, finding that it forms a tetramer with a hydrophobic binding pocket that can
      accommodate retinol. Our results thus identify SAAs as a family of microbe
      inducible retinol binding proteins, reveal a unique protein architecture involved
      in retinol binding, and suggest how retinol is circulated during infection.

PMID- 25073704
TI  - MAP kinase activity supported by BRAF (V600E) mutation rather than gene
      amplification is associated with ETV1 expression in melanoma brain metastases.
AB  - In primary melanoma, ETV1 transcription factor was suggested to be activated
      mainly by gene amplification and to promote tumor growth in cooperation with BRAF
      (V600E) . Aim of this study was to investigate ETV1 expression in human melanoma
      with a focus on brain metastases. We investigated ETV1 in 68 human melanoma brain
      metastases using FISH for ETV1 gene (located at chromosome 7p21) and centromere
      chromosome 7 and immunohistochemistry for ETV1, BRAF (V600E) , and ETV1/BRAF
      associated proteins pMSK1, pRSK1, pp38, pMEK1/2, MAPKAP kinase 2, CIC, HIF-1alpha
      and Ki-67. We further studied ETV1 copy number variations in 32 melanoma cell
      lines from primary and metastatic lesions using array CGH. The influence of the
      MAP kinase pathway activity on ETV1 mRNA and protein expression under BRAF wild
      type and BRAF (V600E) conditions were determined in melanoma cell lines using qRT
      PCR and Western Blot. No ETV1 high grade amplifications were observed in tissue
      samples, but low grade ETV1 gene amplifications were found in 7 (10.3 %) melanoma
      brain metastases. ETV1 protein expression in tissue samples (15 %) correlated
      with BRAF (V600E) status (p = 0.007) and HIF-1alpha expression (p = 0.049), but
      not with ETV1 gene dose. Application of the BRAF(V600E)-specific inhibitor
      vemurafenib and the BRAF(V6ooE/V600K)-inhibitor dabrafenib revealed predominant
      regulation of ETV-1 mRNA and protein via MAPK-pathway. ETV1 expression is a rare
      event in human melanoma and seems to be rather based on hyperactivation of MAPK
      signals, by BRAF (V600E) mutation, than on ETV1 gene amplification. Consequently,
      therapeutic inhibition of BRAF and the downstream MAPK pathway also down
      regulates oncogenic ETV1 expression. 

PMID- 25073706
TI  - Activity-based profiling of a physiologic aglycone library reveals sugar acceptor
      promiscuity of family 1 UDP-glucosyltransferases from grape.
AB  - Monoterpenols serve various biological functions and accumulate in grape (Vitis
      vinifera), where a major fraction occurs as nonvolatile glycosides. We have
      screened the grape genome for sequences with similarity to terpene URIDINE
      DIPHOSPHATE GLYCOSYLTRANSFERASES (UGTs) from Arabidopsis (Arabidopsis thaliana).
      A ripening-related expression pattern was shown for three candidates by spatial
      and temporal expression analyses in five grape cultivars. Transcript accumulation
      correlated with the production of monoterpenyl beta-d-glucosides in grape exocarp
      during ripening and was low in vegetative tissue. Targeted functional screening
      of the recombinant UGTs for their biological substrates was performed by activity
      based metabolite profiling (ABMP) employing a physiologic library of aglycones
      built from glycosides isolated from grape. This approach led to the
      identification of two UDP-glucose:monoterpenol beta-d-glucosyltransferases.
      Whereas VvGT14a glucosylated geraniol, R,S-citronellol, and nerol with similar
      efficiency, the three allelic forms VvGT15a, VvGT15b, and VvGT15c preferred
      geraniol over nerol. Kinetic resolution of R,S-citronellol and R,S-linalool was
      shown for VvGT15a and VvGT14a, respectively. ABMP revealed geraniol as the major
      biological substrate but also disclosed that these UGTs may add to the production
      of further glycoconjugates in planta. ABMP of aglycone libraries provides a
      versatile tool to uncover novel biologically relevant substrates of small
      molecule glycosyltransferases that often show broad sugar acceptor promiscuity. 

PMID- 25073705
TI  - Jasmonic acid and its precursor 12-oxophytodienoic acid control different aspects
      of constitutive and induced herbivore defenses in tomato.
AB  - The jasmonate family of growth regulators includes the isoleucine (Ile) conjugate
      of jasmonic acid (JA-Ile) and its biosynthetic precursor 12-oxophytodienoic acid
      (OPDA) as signaling molecules. To assess the relative contribution of JA/JA-Ile
      and OPDA to insect resistance in tomato (Solanum lycopersicum), we silenced the
      expression of OPDA reductase3 (OPR3) by RNA interference (RNAi). Consistent with
      a block in the biosynthetic pathway downstream of OPDA, OPR3-RNAi plants
      contained wild-type levels of OPDA but failed to accumulate JA or JA-Ile after
      wounding. JA/JA-Ile deficiency in OPR3-RNAi plants resulted in reduced trichome
      formation and impaired monoterpene and sesquiterpene production. The loss of
      these JA/JA-Ile -dependent defense traits rendered them more attractive to the
      specialist herbivore Manduca sexta with respect to feeding and oviposition.
      Oviposition preference resulted from reduced levels of repellant monoterpenes and
      sesquiterpenes. Feeding preference, on the other hand, was caused by increased
      production of cis-3-hexenal acting as a feeding stimulant for M. sexta larvae in
      OPR3-RNAi plants. Despite impaired constitutive defenses and increased
      palatability of OPR3-RNAi leaves, larval development was indistinguishable on
      OPR3-RNAi and wild-type plants, and was much delayed compared with development on
      the jasmonic acid-insensitive1 (jai1) mutant. Apparently, signaling through JAI1,
      the tomato ortholog of the ubiquitin ligase CORONATINE INSENSITIVE1 in
      Arabidopsis (Arabidopsis thaliana), is required for defense, whereas the
      conversion of OPDA to JA/JA-Ile is not. Comparing the signaling activities of
      OPDA and JA/JA-Ile, we found that OPDA can substitute for JA/JA-Ile in the local
      induction of defense gene expression, but the production of JA/JA-Ile is required
      for a systemic response. 

PMID- 25073707
TI  - Intraspecific Arabidopsis hybrids show different patterns of heterosis despite
      the close relatedness of the parental genomes.
AB  - Heterosis is important for agriculture; however, little is known about the
      mechanisms driving hybrid vigor. Ultimately, heterosis depends on the
      interactions of specific alleles and epialleles provided by the parents, which is
      why hybrids can exhibit different levels of heterosis, even within the same
      species. We characterize the development of several intraspecific Arabidopsis
      (Arabidopsis thaliana) F1 hybrids that show different levels of heterosis at
      maturity. We identify several phases of heterosis beginning during embryogenesis
      and culminating in a final phase of vegetative maturity and seed production.
      During each phase, the hybrids show different levels and patterns of growth,
      despite the close relatedness of the parents. For instance, during the vegetative
      phases, the hybrids develop larger leaves than the parents to varied extents, and
      they do so by exploiting increases in cell size and cell numbers in different
      ratios. Consistent with this finding, we observed changes in the expression of
      genes known to regulate leaf size in developing rosettes of the hybrids, with the
      patterns of altered expression differing between combinations. The data show that
      heterosis is dependent on changes in development throughout the growth cycle of
      the hybrid, with the traits of mature vegetative biomass and reproductive yield
      as cumulative outcomes of heterosis at different levels, tissues, and times of
      development. 

PMID- 25073708
TI  - Hemodialysis catheter insertion: is increased PO2 a sign of arterial cannulation?
      A case report.
AB  - BACKGROUND: Ultrasound-guided Central Venous Catheterization (CVC) for temporary
      vascular access, preferably using the right internal jugular vein, is widely
      accepted by nephrologists. However CVC is associated with numerous potential
      complications, including death. We describe the finding of a rare left-sided
      partial anomalous pulmonary vein connection during central venous catheterization
      for continuous renal replacement therapy (CRRT). CASE PRESENTATION: Ultrasound
      guided cannulation of a large bore temporary dual-lumen Quinton-Mahurkar catheter
      into the left internal jugular vein was performed for CRRT initiation in a 66
      year old African-American with sepsis-related oliguric acute kidney injury. The
      post-procedure chest X-ray suggested inadvertent left carotid artery cannulation.
      Blood gases obtained from the catheter showed high partial pressure of oxygen
      (PO2) of 140 mmHg and low partial pressure of carbon dioxide (PCO2) of 22 mmHg,
      suggestive of arterial cannulation. However, the pressure-transduced wave forms
      appeared venous and Computed Tomography Angiography located the catheter in the
      left internal jugular vein, but demonstrated that the tip of the catheter was
      lying over a left pulmonary vein which was abnormally draining into the left
      brachiocephalic (innominate) vein rather than into the left atrium. CONCLUSION:
      Although several mechanical complications of dialysis catheters have been
      described, ours is one of the few cases of malposition into an anomalous
      pulmonary vein, and highlights a sequential approach to properly identify the
      catheter location in this uncommon clinical scenario.

PMID- 25073709
TI  - Inflammatory response in mixed viral-bacterial community-acquired pneumonia.
AB  - BACKGROUND: The role of mixed pneumonia (virus+bacteria) in community-acquired
      pneumonia (CAP) has been described in recent years. However, it is not known
      whether the systemic inflammatory profile is different compared to monomicrobial
      CAP. We wanted to investigate this profile of mixed viral-bacterial infection and
      to compare it to monomicrobial bacterial or viral CAP. METHODS: We measured
      baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood
      cell (WBC) count in 171 patients with CAP with definite etiology admitted to a
      tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed
      (viral-bacterial). RESULTS: Serum PCT levels were higher in mixed and bacterial
      CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the
      other groups. CRP was independently associated with mixed CAP. CRP levels below
      26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the
      positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive
      predictive value for bacterial-involved CAP versus viral CAP of 78%, but the
      negative predictive value was 48%. CONCLUSIONS: Mixed CAP has a different
      inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be
      useful for clinicians to suspect mixed CAP.

PMID- 25073710
TI  - A study of snake bite among children presenting to a paediatric ward in the main
      Teaching Hospital of North Central province of Sri Lanka.
AB  - BACKGROUND: Snake bite is a common problem in the North Central province of Sri
      Lanka. Common krait (Bungarus careuleus), Ceylon krait (Bungarus ceylonicus),
      Cobra (Naja naja), Russell's viper (Daboia russelii), Saw-scaled viper (Echis
      carinatus) and Hump-nosed pit viper (Hypnale hypnale) are the six species of
      venomous land snakes in Sri Lanka. A significant number of adults and children
      are bitten by snakes every year. However, the majority of research studies done
      in Sri Lanka and other countries show adults bitten by snakes and studies
      describing children bitten by snakes are very sparse. METHODS: A descriptive
      cross sectional study was performed in the Teaching Hospital Anuradhapura in the
      North Central Province of Sri Lanka from May 2010 to 2011 May to describe the
      characteristics associated with cases of snake bite. RESULTS: There were 24 males
      and 20 females. The highest numbers of bites (48%) were in the range of ages 6-12
      years. The majority of the bites occurred between 6 pm to 6 am (59%).The foot was
      the most common bitten site (48%). Out of all the venomous bites, the Hump-nosed
      pit viper (Hypnale hypnale) accounted for the highest number (44%) and Russell's
      viper (Daboia ruselii) accounted for the second highest number (27%). A
      significant number of venomous bites occurred indoors while sleeping (22%).
      Antivenom serum was given to (39%) of venomous bites. Deaths occurred in (11%) of
      the venomous bites. CONCLUSIONS: Hump-nosed pit viper (Hypnale hypnale) accounted
      for the highest number of venomous bites. Majority of the bites occurred between
      6 pm and 6 am. Foot was the most common bitten site. A significant number of
      venomous bites occurred indoor while sleeping. Antivenom serum was given to a
      significant number of venomous bites. Educating the public on making their houses
      snake proof and using a torch when going out during night time will help in the
      prevention of getting bitten by snakes.

PMID- 25073711
TI  - Marshall syndrome: further evidence of a distinct phenotypic entity and report of
      new findings.
AB  - Marshall syndrome and type II Stickler syndrome are caused by mutations in
      COL11A1, which codes for the proalpha1chain of collagen XI. Collagen XI is a
      minor fibrillar collagen co-expressed with collagen II in cartilage and the
      vitreous of the eye. Characteristic features of Marshall syndrome include
      midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Deletions,
      insertions, splice site, and missense mutations in COL11A1 have been identified
      in Stickler syndrome and Marshall syndrome patients. In this study, we describe
      the clinical presentations of seven patients with Marshall syndrome from three
      unrelated Saudi families, inherited as autosomal dominant (two families) and
      autosomal recessive (one family). Cardinal clinical features of Marshall syndrome
      are manifested in all patients. One patient had ectodermal abnormalities.
      Mutations (c.2702G > A in exon 34,IVS50 + 1G > A, and IVS50 + lG > C) were
      identified in COL11A1 in affected members. Interestingly, the first report of
      autosomal recessive Marshall syndrome was from Saudi Arabia caused by the same
      mutation (c.2702G > A, p.Gly901Glu) as in one of our families. This study depicts
      detailed phenotypic and genetic description of dominant and recessive forms of
      Marshall syndrome due to COL11A1 mutations.

PMID- 25073712
TI  - Medical professionalism across cultures: a challenge for medicine and medical
      education.
AB  - BACKGROUND: The recognition of medical professionalism as a complex social
      construct makes context, geographical location and culture important
      considerations in any discussion of professional behaviour. Medical students,
      medical educators and practitioners are now much more on the move globally,
      exposing them to cultural and social attitudes, values and beliefs that may
      differ from their own traditional perceptions of professionalism. AIMS AND
      METHODS: This paper uses the model of the intercultural development continuum and
      the concept of "cultural fit" to discuss what might transpire when a student,
      teacher or doctor is faced with a new cultural environment. Using our own
      experiences as medical educators working abroad and supported by evidence in the
      literature, we have developed four anecdotal scenarios to highlight some of the
      challenges that different cultural contexts bring to our current (Western)
      understanding of professionalism. RESULTS AND CONCLUSIONS: The scenarios
      highlight some of the potentially different regional and/or cultural perspectives
      and nuances of professional behaviours, attitudes or values that many of us
      either take for granted or find difficult, depending on our training and socio
      cultural upbringing. With this paper, we hope to start a long overdue
      conversation about global professionalism amongst medical educators, identify
      potential areas for research and highlight a need for medical schools to embrace
      a "global" approach to how professionalism is embedded in their curricula.

PMID- 25073714
TI  - A metabolomic strategy to screen the prototype components and metabolites of
      Qingkailing injection in rat urine by high-performance liquid chromatography with
      tandem mass spectrometry.
AB  - Xenobiotic metabolome identification of Chinese herbal formula in biological
      systems is a very challenging task. Qingkailing injection is a typical Chinese
      herbal injection, which is wildly used clinically in China. However, the holistic
      metabolic fate of the ingredient from Qingkailing injection remains unclear. In
      this work, a metabolomic strategy for comprehensively elucidating Qingkailing
      injection derived prototype components and metabolites in rat urine conducted by
      hybrid linear ion trap high-resolution mass spectrometry was developed. High
      performance liquid chromatography coupled with hybrid linear ion trap high
      resolution mass spectrometry was developed to obtain the urine profiling between
      the control group and Qingkailing injection treated group. Orthogonal partial
      least squares discriminate analysis was applied to distinguish the exogenous and
      the endogenous. In the S-plot, 37 xenobiotics derived from Qingkailing injection
      were found in urine, including 18 prototype compounds and 19 metabolites. The
      characterization of the prototype components and metabolites in rat's urine
      provided essential data for further pharmacological studies of Qingkailing
      injection. Our results indicated that the metabolomic approach was an effective
      tool to discover, screen, and analyze the multiple prototype components and their
      metabolites from complicated traditional Chinese preparations in vivo. 

PMID- 25073713
TI  - The association between lifetime smoking exposure and breast cancer mortality-
      results from a Norwegian cohort.
AB  - Several recent cohort studies have found an association between smoking and
      breast cancer, but the association between lifetime smoking exposure and breast
      cancer mortality is less well described. We examined whether smoking before
      breast cancer diagnosis is a predictor of breast cancer mortality in a large
      cohort with more than 4.1 million years of follow-up, with a special focus on
      women who initiated smoking before first childbirth. Information on smoking
      status was collected before breast cancer diagnosis and used to estimate hazard
      ratios (HRs) and corresponding 95% confidence intervals (CIs) of breast cancer
      mortality in a cohort of 302,865 Norwegian women with 1106 breast cancer deaths.
      Women were enrolled between 1974 and 2003 and followed up through linkages to
      national registries until 31 December 2007. We found that breast cancer mortality
      was slightly but significantly increased for current (HR = 1.15, 95% CI 1.01
      1.32) and ever (HR = 1.15, 95% CI 1.02-1.30) smokers as compared to never
      smokers. No statistically significantly increased mortality was found for women
      who initiated smoking before first childbirth, and no dose-response association
      was revealed for any of the different measures of smoking exposure. A large
      proportion of heavy smokers may have died from other causes than breast cancer
      during follow-up, possibly diluting our results. This study found that lifetime
      smoking exposure had a significantly increased risk of breast cancer mortality
      compared with never smokers. 

PMID- 25073715
TI  - Effects of phonation time and magnitude dose on vocal fold epithelial genes,
      barrier integrity, and function.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the effects of increasing time and
      magnitude doses of vibration exposure on transcription of the vocal fold's
      junctional proteins, structural alterations, and functional tissue outcomes.
      STUDY DESIGN: Animal study. METHODS: 100 New Zealand White breeder rabbits were
      studied. Dependent variables were measured in response to increasing time doses
      (30, 60, or 120 minutes) and magnitude doses (control, modal intensity, and
      raised intensity) of vibration exposure. Messenger RNA expression of occludin,
      zonula occluden-1 (ZO-1), E-cadherin, beta-catenin, interleukin 1beta,
      cyclooxygenase-2, transforming growth factor beta-1, and fibronectin were
      measured. Tissue structural alterations were assessed using transmission electron
      microscopy (TEM). Transepithelial resistance was used to measure functional
      tissue outcomes. RESULTS: Occludin gene expression was downregulated in vocal
      folds exposed to 120-minute time doses of raised-intensity phonation, relative to
      control, and modal-intensity phonation. ZO-1 gene expression was upregulated
      following a 120-minute time dose of modal-intensity phonation, compared to
      control, and downregulated after a 120-minute time dose of raised-intensity
      phonation, compared to modal-intensity phonation. E-cadherin gene expression was
      downregulated after a 120-minute time dose of raised-intensity phonation,
      compared to control and modal-intensity phonation. TEM revealed extensive
      desquamation of the stratified squamous epithelial cells with increasing time and
      magnitude doses of vibration exposure. A general observation of lower
      transepithelial resistance measures was made in tissues exposed to raised
      intensity phonation compared to all other groups. CONCLUSIONS: This study
      provides evidence of vocal fold tissue responses to varying time and magnitude
      doses of vibration exposure. LEVEL OF EVIDENCE: NA.

PMID- 25073716
TI  - Inhibition of STAT3 signalling contributes to the antimelanoma action of
      atractylenolide II.
AB  - Our previous studies showed that atractylenolide II (AT-II) has antimelanoma
      effects in B16 melanoma cells. In this study, we investigated the involvement of
      STAT3 signalling in the antimelanoma action of AT-II. Daily administration of AT
      II (12.5, 25 mg/kg, i.g.) for 14 days significantly inhibited tumor growth in a
      B16 xenograft mouse model and inhibited the activation/phosphorylation of STAT3
      and Src in the xenografts. In B16 and A375 cells, AT-II (20, 40 MUm) treatment
      for 48 h dose-dependently reduced protein expression levels of phospho-STAT3,
      phospho-Src, as well as STAT3-regulated Mcl-1 and Bcl-xL. Overexpression of a
      constitutively active variant of STAT3, STAT3C in A375 cells diminished the
      antiproliferative and apoptotic effects of AT-II. These data suggest that
      inhibition of STAT3 signalling contributes to the antimelanoma action of AT-II.
      Our findings shed new light on the mechanism of action underlying the
      antimelanoma effects of AT-II and provide further pharmacological basis for
      developing AT-II as a novel melanoma chemopreventive/chemotherapeutic agent. 

PMID- 25073718
TI  - Medication risk communication during rheumatology office visits.
AB  - OBJECTIVE: We used a multidimensional framework to describe the types of
      information about medication risks that rheumatologists provide to rheumatoid
      arthritis (RA) patients during routine office visits. METHODS: We analyzed 1,094
      audiotaped rheumatology office visits involving 450 RA patients. Each patient had
      up to 3 visits audiotaped. In conjunction with each office visit, patients also
      completed a self-administered questionnaire and interview and the rheumatologists
      provided ratings of patient health status. RESULTS: The number of medication
      risks discussed per visit ranged from 0-18, with a mean +/- SD of 3.23 +/- 2.93.
      The rheumatologist initiated ~80% of the medication risk discussions.
      Approximately one-fourth of the discussions (25.6%) were limited to an assessment
      of whether or not the patient was experiencing a medication side effect. More
      risks were discussed during visits when changes to the patient's regimen were
      discussed than when no changes were discussed (X= 3.93, SD = 3.10 and X = 2.20,
      SD = 2.34, respectively; P < 0.0001). When medications were being proposed for
      addition to the patient's regimen, the most frequently discussed risk dimensions
      were the importance of monitoring (30%), probability (29.8%), things the patient
      should do to minimize risk (25.5%), and risk severity (21.8%). CONCLUSION: Most
      discussions of medication risks that we observed were quite limited and often
      restricted to an assessment of whether the patient was experiencing side effects
      from their current medications. The amount of information that is optimal and how
      to tailor information to the preferences and abilities of individual patients
      remain important areas for future research.

PMID- 25073717
TI  - People with Parkinson's disease and normal MMSE score have a broad range of
      cognitive performance.
AB  - Cognitive impairment, including dementia, is common in Parkinson's disease (PD).
      The Mini-Mental State Examination (MMSE) has been recommended as a screening tool
      for Parkinson's disease dementia (PDD), with values below 26 indicative of
      possible dementia. Using a detailed neuropsychological battery, we examined the
      range of cognitive impairment in PD patients with an MMSE score of 26 or higher.
      In this multicenter, cross-sectional, observational study, we performed
      neuropsychological testing in a sample of 788 PD patients with MMSE scores of 26
      or higher. Evaluation included tests of global cognition, executive function,
      language, memory, and visuospatial skills. A consensus panel reviewed results for
      342 subjects and assigned a diagnosis of no cognitive impairment, mild cognitive
      impairment, or dementia. Sixty-seven percent of the 788 subjects performed 1.5
      standard deviations below the normative mean on at least one test. On eight of
      the 15 tests, more than 20% of subjects scored 1.5 standard deviations or more
      below the normative mean. Greatest impairments were found on Hopkins Verbal
      Learning and Digit Symbol Coding tests. The sensitivity of the MMSE to detect
      dementia was 45% in a subset of participants who underwent clinical diagnostic
      procedures. A remarkably wide range of cognitive impairment can be found in PD
      patients with a relatively high score on the MMSE, including a level of cognitive
      impairment consistent with dementia. Given these findings, clinicians must be
      aware of the limitations of the MMSE in detecting cognitive impairment, including
      dementia, in PD.

PMID- 25073719
TI  - Automated real-time text messaging as a means for rapidly identifying acute
      stroke patients for clinical trials.
AB  - BACKGROUND: Recruiting stroke patients into acute treatment trials is challenging
      because of the urgency of clinical diagnosis, treatment, and trial inclusion.
      Automated alerts that identify emergency patients promptly may improve trial
      performance. The main purposes of this project were to develop an automated real
      time text messaging system to immediately inform physicians of patients with
      suspected stroke and to test its feasibility in the emergency setting. METHODS:
      An electronic standardized stroke algorithm (SSA) was implemented in the clinical
      information system (CIS) and linked to a remote data capture system. Within 10
      minutes following the documentation and storage of basic information to CIS, a
      text message was triggered for patients with suspected stroke and sent to a
      dedicated trial physician. Each text message provided anonymized information on
      the exact department and unit, date and time of admission, age, sex, and National
      Institute of Health Stroke Scale (NIHSS) of the patient. All necessary
      information needed to generate a text message was already available - routine
      processes in the emergency department were not affected by the automated real
      time text messaging system. The system was tested for three 4-week periods.
      Feasibility was analyzed based on the number of patients correctly identified by
      the SSA and the door-to-message time. RESULTS: In total, 513 text messages were
      generated for patients with suspected stroke (median age 74 years (19-106); 50.3%
      female; median NIHSS 4 (0-41)), representing 96.6% of all cases. For 48.3% of
      these text messages, basic documentation was completed within less than 1 hour
      and a text message was sent within 60 minutes after patient admission.
      CONCLUSIONS: The system proved to be stable in generating text messages using IT
      based CIS to identify acute stroke trial patients. The system operated on
      information which is documented routinely and did not result in a higher
      workload. Delays between patient admission and the text message were caused by
      delayed completion of basic documentation. To use the automated real-time text
      messaging system to immediately identify emergency patients suitable for acute
      stroke trials, further development needs to focus on eliminating delays in
      documentation for the SSA in the emergency department.

PMID- 25073720
TI  - Brain State Differentiation and Behavioral Inflexibility in Autism.
AB  - Autism spectrum disorders (ASDs) are characterized by social impairments
      alongside cognitive and behavioral inflexibility. While social deficits in ASDs
      have extensively been characterized, the neurobiological basis of inflexibility
      and its relation to core clinical symptoms of the disorder are unknown. We
      acquired functional neuroimaging data from 2 cohorts, each consisting of 17
      children with ASDs and 17 age- and IQ-matched typically developing (TD) children,
      during stimulus-evoked brain states involving performance of social attention and
      numerical problem solving tasks, as well as during intrinsic, resting brain
      states. Effective connectivity between key nodes of the salience network, default
      mode network, and central executive network was used to obtain indices of
      functional organization across evoked and intrinsic brain states. In both cohorts
      examined, a machine learning algorithm was able to discriminate intrinsic
      (resting) and evoked (task) functional brain network configurations more
      accurately in TD children than in children with ASD. Brain state discriminability
      was related to severity of restricted and repetitive behaviors, indicating that
      weak modulation of brain states may contribute to behavioral inflexibility in
      ASD. These findings provide novel evidence for a potential link between
      neurophysiological inflexibility and core symptoms of this complex
      neurodevelopmental disorder. 

PMID- 25073721
TI  - The BiSciCol Triplifier: bringing biodiversity data to the Semantic Web.
AB  - BACKGROUND: Recent years have brought great progress in efforts to digitize the
      world's biodiversity data, but integrating data from many different providers,
      and across research domains, remains challenging. Semantic Web technologies have
      been widely recognized by biodiversity scientists for their potential to help
      solve this problem, yet these technologies have so far seen little use for
      biodiversity data. Such slow uptake has been due, in part, to the relative
      complexity of Semantic Web technologies along with a lack of domain-specific
      software tools to help non-experts publish their data to the Semantic Web.
      RESULTS: The BiSciCol Triplifier is new software that greatly simplifies the
      process of converting biodiversity data in standard, tabular formats, such as
      Darwin Core-Archives, into Semantic Web-ready Resource Description Framework
      (RDF) representations. The Triplifier uses a vocabulary based on the popular
      Darwin Core standard, includes both Web-based and command-line interfaces, and is
      fully open-source software. CONCLUSIONS: Unlike most other RDF conversion tools,
      the Triplifier does not require detailed familiarity with core Semantic Web
      technologies, and it is tailored to a widely popular biodiversity data format and
      vocabulary standard. As a result, the Triplifier can often fully automate the
      conversion of biodiversity data to RDF, thereby making the Semantic Web much more
      accessible to biodiversity scientists who might otherwise have relatively little
      knowledge of Semantic Web technologies. Easy availability of biodiversity data as
      RDF will allow researchers to combine data from disparate sources and analyze
      them with powerful linked data querying tools. However, before software like the
      Triplifier, and Semantic Web technologies in general, can reach their full
      potential for biodiversity science, the biodiversity informatics community must
      address several critical challenges, such as the widespread failure to use
      robust, globally unique identifiers for biodiversity data.

PMID- 25073722
TI  - Cardiovascular disease in psoriatic post-menopausal women.
AB  - BACKGROUND: It is generally accepted that the risk of cardiovascular disease
      (CVD) in women is significantly increased after the menopause. Hormonal changes
      associated with the menopausal transition may also alter the course of autoimmune
      diseases. It has been reported that menopause may exacerbate the symptoms of
      rheumatoid arthritis, systemic sclerosis and giant cell arteritis, but attenuate
      the course of systemic lupus erythemathosus. There is a growing body of
      literature indicating that the course of psoriasis may be altered by menopausal
      hormone changes. Considering the fact that both psoriasis and menopause are
      independent risk factors for CVD, and that menopause may exacerbate the course of
      psoriasis, a possible additive effect between these two conditions may be crucial
      for proper monitoring and treatment of peri- and post-menopausal psoriatic
      patients. OBJECTIVE: The aim of this study is to analyse potential relationship
      between psoriasis, menopausal status and risk of CVD. MATERIALS AND METHODS: A
      retrospective analysis of the Clalit Health Services database was performed in an
      attempt to provide new data and the available literature concerning these issues
      was reviewed. Data on cardiovascular events in 10 872 female psoriatic patients
      and 19 471 controls were extracted and compared. RESULTS: In both psoriatic and
      control patients the association of CVD increased with age. The association of
      CVD was significantly greater in psoriatic patients, but no significant
      differences were found between any of age groups. CONCLUSIONS: The association of
      psoriasis and CVD in women increases with age but there is insufficient evidence
      to confirm that menopause increases the risk of psoriasis. Further studies
      directly addressing this issue are needed.

PMID- 25073724
TI  - Development of simple, rapid and sensitive detection assay for grouper nervous
      necrosis virus using real-time loop-mediated isothermal amplification.
AB  - A quantitative rapid detection method based on loop-mediated isothermal
      amplification has been developed for red-spotted grouper nervous necrosis virus
      (RGNNV). The nested polymerase chain reaction (PCR) assay is the mainstream
      inspection of the brooder in the hatchery. In this study, a real-time loop
      mediated isothermal amplification (LAMP) method has been applied for RGNNV
      detection, known as a high-speed gene amplification procedure. Of the three
      temperatures (60  degrees C, 63  degrees C and 65  degrees C) attempted, it has
      been found that 63  degrees C is giving higher amplification from 11th minute
      onwards. Sensitivity analysis performed in comparison with real-time polymerase
      chain reaction, reverse transcriptase PCR and nested RT-PCR using various
      concentrations of template revealed that real-time LAMP method is efficient in
      terms of cost and time consumption. Specificity analysis revealed that the method
      developed is specific to RGNNV, whereas it has sequence cross-match with tiger
      puffer NNV giving advantage in detecting both the viruses. This method could be
      much efficient in analysing RGNNV in combination with TPNNV.

PMID- 25073723
TI  - Endothelial atypical cannabinoid receptor: do we have enough evidence?
AB  - Cannabinoids and their synthetic analogues affect a broad range of physiological
      functions, including cardiovascular variables. Although direct evidence is still
      missing, the relaxation of a vast range of vascular beds induced by cannabinoids
      is believed to involve a still unidentified non-CB1 , non-CB2 Gi/o protein
      coupled receptor located on endothelial cells, the so called endothelial
      cannabinoid receptor (eCB receptor). Evidence for the presence of an eCB receptor
      comes mainly from vascular relaxation studies, which commonly employ pertussis
      toxin as an indicator for GPCR-mediated signalling. In addition, a
      pharmacological approach is widely used to attribute the relaxation to eCB
      receptors. Recent findings have indicated a number of GPCR-independent targets
      for both agonists and antagonists of the presumed eCB receptor, warranting
      further investigations and cautious interpretation of the vascular relaxation
      studies. This review will provide a brief historical overview on the proposed
      novel eCB receptor, drawing attention to the discrepancies between the studies on
      the pharmacological profile of the eCB receptor and highlighting the Gi/o protein
      independent actions of the eCB receptor inhibitors widely used as selective
      compounds. As the eCB receptor represents an attractive pharmacological target
      for a number of cardiovascular abnormalities, defining its molecular identity and
      the extent of its regulation of vascular function will have important
      implications for drug discovery. This review highlights the need to re-evaluate
      this subject in a thoughtful and rigorous fashion. More studies are needed to
      differentiate Gi/o protein-dependent endothelial cannabinoid signalling from that
      involving the classical CB1 and CB2 receptors as well as its relevance for
      pathophysiological conditions. 

PMID- 25073725
TI  - Comparison of liver biopsy and noninvasive techniques for liver fibrosis
      assessment in patients infected with HCV-genotype 4 in Egypt.
AB  - In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess
      liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a
      treatment should be proposed. Many of its disadvantages have led to develop
      noninvasive methods to replace LB. These new methods should be evaluated in
      Egypt, where circulating virus genotype 4 (G4), increased body mass index and co
      infection with schistosomiasis may interfere with liver fibrosis assessment.
      Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement
      (Fibroscan((c))), and serum markers (APRI, Fib4 and Fibrotest((c))). Patients had
      to have a LB >=15 mm length or >=10 portal tracts with two pathologists blinded
      readings to be included in the analysis. Patients with hepatitis B virus co
      infection were excluded. Three hundred and twelve patients are reported. The
      performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The
      area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75
      for APRI, Fib-4, Fibrotest(c) and Fibroscan(c), respectively (no influence of
      schistosomiasis was noticed). An algorithm using the Fib4 for identifying
      patients with F2 stage or more reduced by nearly 90% the number of liver
      biopsies. Our results demonstrated that noninvasive techniques were feasible in
      Egypt, for CHC G4-infected patients. Because of its validity and its easiness to
      perform, we believe that Fib4 may be used to assess the F2 threshold, which
      decides whether treatment should be proposed or delayed.

PMID- 25073726
TI  - Shoulder motor performance assessment in the sagittal plane in children with
      hemiplegia during single joint pointing tasks.
AB  - BACKGROUND: Pointing is a motor task extensively used during daily life
      activities and it requires complex visuo-motor transformation to select the
      appropriate movement strategy. The study of invariant characteristics of human
      movements has led to several theories on how the brain solves the redundancy
      problem, but the application of these theories on children affected by hemiplegia
      is limited. This study aims at giving a quantitative assessment of the shoulder
      motor behaviour in children with hemiplegia during pointing tasks. METHODS: Eight
      children with hemiplegia were involved in the study and were asked to perform
      movements on the sagittal plane with both arms, at low and high speed. Subject
      movements were recorded using an optoelectronic system; a 4-DOF model of children
      arm has been developed to calculate kinematic and dynamic variables. A set of
      evaluation indexes has been extracted in order to quantitatively assess whether
      and how children modify their motor control strategies when perform movements
      with the more affected or less affected arm. RESULTS: In low speed movements, no
      differences can be seen in terms of movement duration and peak velocity between
      the More Affected arm (MA) and the Less Affected arm (LA), as well as in the main
      characteristics of movement kinematics and dynamics. As regards fast movements,
      remarkable differences in terms of strategies of motor control can be observed:
      while movements with LA did not show any significant difference in Dimensionless
      Jerk Index (JI) and Dimensionless Torque-change Cost index (TC) between the
      elevation and lowering phases, suggesting that motor control optimization is
      similar for movements performed with or against gravity, movements with MA showed
      a statistically significant increase of both JI and TC during lowering phase.
      CONCLUSIONS: Results suggest the presence of a different control strategy for
      fast movements in particular during lowering phase. Results suggest that motor
      control is not able to optimize Jerk and Torque-change cost functions in the same
      way when controls the two arms, suggesting that children with hemiplegia do not
      actively control MA lowering fast movements, in order to take advantage of the
      passive inertial body properties, rather than to attempt its optimal control.

PMID- 25073727
TI  - Comparative metabolomic analysis of wild type and mads3 mutant rice anthers.
AB  - Rice (Oryza sativa L.) MADS3 transcription factor regulates the homeostasis of
      reactive oxygen species (ROS) during late anther development, and one MADS3
      mutant, mads3-4, has defective anther walls, aborted microspores and complete
      male sterility. Here, we report the untargeted metabolomic analysis of both wild
      type and mads3-4 mature anthers. Mutation of MADS3 led to an unbalanced redox
      status and caused oxidative stress that damages lipid, protein, and DNA. To cope
      with oxidative stress in mads3-4 anthers, soluble sugars were mobilized and
      carbohydrate metabolism was shifted to amino acid and nucleic acid metabolism to
      provide substrates for the biosynthesis of antioxidant proteins and the repair of
      DNA. Mutation of MADS3 also affected other aspects of rice anther development
      such as secondary metabolites associated with cuticle, cell wall, and auxin
      metabolism. Many of the discovered metabolic changes in mads3-4 anthers were
      corroborated with changes of expression levels of corresponding metabolic pathway
      genes. Altogether, this comparative metabolomic analysis indicated that MADS3
      gene affects rice anther development far beyond the ROS homeostasis regulation. 

PMID- 25073728
TI  - pH-responsive magnetic core-shell nanocomposites for drug delivery.
AB  - Polymer-modified nanoparticles, which can load anticancer drugs such as
      doxorubicin (DOX), showing the release in response to a specific trigger, have
      been paid much attention in cancer therapy. In our study, a pH-sensitive drug
      delivery system consisting of Fe3O4@mSiO2 core-shell nanocomposite (about 65 nm)
      and a beta-thiopropionate-poly(ethylene glycol) "gatekeeper" (P2) has been
      successfully synthesized as a drug carrier (Fe3O4@mSiO2@P2). Because of the
      hydrolysis of the beta-thiopropionate linker under mildly acidic conditions,
      Fe3O4@mSiO2@P2 shows a pH-sensitive release performance based on the slight
      difference between a tumor (weakly acid) and normal tissue (weakly alkaline). And
      before reaching the tumor site, the drug-delivery system shows good drug
      retention. Notably, the nanocomposites are quickly taken up by HeLa cells due to
      their small particle size and the poly(ethylene glycol) modification, which is
      significant for increasing the drug efficiency as well as the cancer therapy of
      the drug vehicles. The excellent biocompatibility and selective release
      performance of the nanocomposites combined with the magnetic targeted ability are
      expected to be promising in the potential application of cancer treatment. 

PMID- 25073729
TI  - Predominance of biotic over abiotic formation of halogenated hydrocarbons in
      hypersaline sediments in Western Australia.
AB  - Volatile halogenated organic compounds (VOX) contribute to ozone depletion and
      global warming. There is evidence of natural VOX formation in many environments
      ranging from forest soils to salt lakes. Laboratory studies have suggested that
      VOX formation can be chemically stimulated by reactive Fe species while field
      studies have provided evidence for direct biological (enzymatic) VOX formation.
      However, the relative contribution of abiotic and biotic processes to global VOX
      budgets is still unclear. The goals of this study were to quantify VOX release
      from sediments from a hypersaline lake in Western Australia (Lake Strawbridge)
      and to distinguish between the relative contributions of biotic and abiotic VOX
      formation in microbially active and sterilized microcosms. Our experiments
      demonstrated that the release of organochlorines from Lake Strawbridge sediments
      was mainly biotic. Among the organochlorines detected were monochlorinated, e.g.,
      chloromethane (CH3Cl), and higher chlorinated VOX compounds such as
      trichloromethane (CHCl3). Amendment of sediments with either Fe(III) oxyhydroxide
      (ferrihydrite) or a mixture of lactate/acetate or both ferrihydrite and
      lactate/acetate did not stimulate VOX formation. This suggests that although
      microbial Fe(III) reduction took place, there was no stimulation of VOX formation
      via Fe redox transformations or the formation of reactive Fe species under our
      experimental conditions. 

PMID- 25073730
TI  - pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug
      delivery.
AB  - We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)
      4beta-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4beta
      aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and
      self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles
      simultaneously served as an anticancer drug conjugate and as drug carriers. As a
      drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a
      mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was
      confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei
      of the tumor cells and led to much more cytotoxic effects to A549, Hela, and
      HepG2 cancer cells than the parent NPOD. The half maximal inhibitory
      concentration (IC50) of mPEG-NPOD-I was about one order magnitude lower than that
      of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly,
      and the biodistribution studies indicated that this drug conjugate could
      selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I
      micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and
      drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release
      behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD
      I/PTX. We are convinced that these multifunctional drug conjugate micelles have
      tremendous potential for targeted cancer therapy.

PMID- 25073731
TI  - Births: preliminary data for 2009.
AB  - Objectives-This report presents preliminary data for 2009 on births in the United
      States. U.S. data on births are shown by age, live-birth order, race, and
      Hispanic origin of mother. Data on marital status, cesarean delivery, preterm
      births, and low birthweight (LBW) are also presented. Methods-Data in this report
      are based on 99.95 percent of births for 2009. The records are weighted to
      independent control counts of all births received in state vital statistics
      offices in 2009. Comparisons are made with final 2008 data. Results-The 2009
      preliminary number of U.S. births declined 3 percent from 2008, to 4,131,019; the
      2009 general fertility rate (66.7 per 1,000 women) and the total fertility rate
      (2,007.5 births per 1,000 women) declined (3 to 4 percent). The number of births
      and birth rates declined for all race and Hispanic origin groups in 2009. c The
      birth rate for U.S. teenagers 15-19 years fell 6 percent to 39.1 per 1,000, a
      record low for the United States. c Birth rates for younger and older teenagers
      and for Hispanic, non-Hispanic white, non-Hispanic black, and Asian or Pacific
      Islander teenagers all reached historic lows in 2009. c The birth rates for women
      in their early 20s fell (7 percent, the largest percentage decline for this age
      group since 1973), as did the rates for women in their late 20s and 30s; the
      birth rate for women in their early 40s increased in 2009. c The birth rate for
      unmarried women declined almost 4 percent to 50.6 per 1,000 aged 15-44. The
      number of nonmarital births fell 2 percent to 1,693,850 in 2009, the first
      decline since 1996-1997. c The percentage of births to unmarried women, however,
      continued to increase in 2009. c The cesarean delivery rate rose to 32.9 percent
      in 2009, another record high. c The preterm birth rate declined for the third
      straight year to 12.18 percent of all births. c The LBW rate was essentially
      unchanged between 2008 and 2009 at 8.16 percent in 2009 but is down from 2006. 

PMID- 25073732
TI  - Pain tolerance, pain sensitivity, and accessibility of aggression-related
      schemata in parents at-risk for child physical abuse.
AB  - This study examined whether parents with varying degrees of child physical abuse
      (CPA) risk differed in pain tolerance, pain sensitivity, and accessibility of
      aggression-related schemata. Participants included 91 (51 low CPA risk and 40
      high CPA risk) general population parents. Participants were randomly assigned to
      complete either an easy or a difficult anagram task. Pain tolerance and pain
      sensitivity were assessed using a cold pressor task. Accessibility of aggression
      related schemata was assessed at the outset of the data collection session and at
      the end of the session using a word completion task. Parents' self-reported
      negative affect was assessed three times over the course of the study: baseline,
      after the anagram task, and after the cold pressor task. As expected, high-risk
      (compared to low-risk) parents reported higher levels of negative affect at each
      time point. Moreover, after completing the difficult anagram task, high-risk
      (compared to low-risk) parents exhibited higher pain sensitivity during the cold
      pressor task. Following completion of the cold pressor task, high-risk (compared
      to low-risk) parents exhibited greater accessibility of aggression-related
      schemata. Collectively, these findings indicate that under certain conditions,
      high-risk parents experience a confluence of aggression-related risk factors
      (i.e., negative affect, pain sensitivity, and aggression-related information
      processes) that may predispose them to aggressive behavior. 

PMID- 25073733
TI  - Posttraumatic stress mediates the relationship between childhood victimization
      and current mental health burden in newly incarcerated adults.
AB  - The purpose of this study was to evaluate the interrelationship among childhood
      abuse and traumatic loss, posttraumatic stress symptoms (PTSS), and Axis I
      psychiatric disorders other than PTSD among newly incarcerated adults, and to
      test a proposed model in which the severity of PTSS mediates the relationship
      between childhood abuse/loss and adult psychiatric disorders. Four hundred sixty
      five male and female inmates participated in a structured clinical research
      interview. Four types of interpersonal potentially traumatic experiences
      (physical abuse, sexual abuse, emotional abuse, and traumatic loss) were assessed
      for occurrence prior to the age of 18 years old. Current psychiatric disorders
      and PTSS were also assessed by structured interview. Negative binomial regression
      was used to evaluate the association between the cumulative number of types of
      childhood abuse/loss experienced and number of current Axis I disorders, and to
      test the mediation model. Approximately half of the sample (51%) experienced 1 or
      more types of childhood abuse/loss, and 30% of the sample had at least one
      psychiatric disorder other than PTSD. For both men and women, childhood physical
      abuse and childhood sexual abuse were independently associated with psychiatric
      morbidity, and an increasing number of types of childhood trauma experienced was
      associated with an increase in the number of current Axis I diagnoses. However,
      these associations were no longer statistically significant when severity of PTSS
      was added to the model, providing support for the proposed mediation model.
      Implications for secondary prevention services for at-risk inmates are discussed.

PMID- 25073734
TI  - Relationship between melanoma detection pattern and tumor thickness.
AB  - BACKGROUND: Melanoma tumor thickness remains the most important determinant of
      patient survival. Several large population-based studies have shown that full
      body skin examinations (FBSE) improve melanoma mortality and others that FBSEs
      may detect melanomas at a thinner, more curable stage. PURPOSE: To relate the
      detection method to lesion thickness at the time of diagnosis. METHODS: A
      retrospective chart review of all cases of biopsy-proven primary cutaneous
      melanomas diagnosed from 2000 to 2012 at the Veterans Affairs Hospital in
      Brooklyn NY was conducted. Data were collected in 2012-2013 and analyzed in 2013.
      Main outcome measures include lesion thickness stratified by method of detection
      and probabilities of detecting thin lesions per method (using cut-offs of in situ
      and 0.75 mm). Secondary outcomes include interaction between method and body site
      or lesion diameter. RESULTS: Sixty-three percent of melanomas were detected by
      FBSE and 59% of all melanomas were in situ. There was no statistically
      significant difference in thickness among the detection groups when a cut-off of
      in situ (Fisher's exact test, p=0.6148) or 0.75 mm was used (p=0.8910). A
      majority of lesions on the back were found by FBSE (68%). CONCLUSIONS: FBSE was
      not shown to detect melanomas at a thinner stage. Prospective studies are needed
      to analyze the utility and efficacy of FBSEs in clinical practice.

PMID- 25073735
TI  - Cardiovascular and ocular safety of alpha1-adrenoceptor antagonists in the
      treatment of male lower urinary tract symptoms.
AB  - INTRODUCTION: alpha1-Adrenoceptor antagonists (alpha-blockers) represent first
      line drug treatment for male lower urinary tract symptoms. Their adverse events
      (AEs) include asthenia, dizziness, nasal congestion, arterial (orthostatic)
      hypotension and intraoperative floppy iris syndrome (IFIS). AREAS COVERED: This
      report focuses on cardiovascular and ocular AEs of alpha-blockers as related to
      their mechanism of action and subtype selectivity. EXPERT OPINION: The incidence
      of hypotension differs between alpha-blockers. It is greatest with doxazosin or
      terazosin, but others including tamsulosin can also lead to hypotension
      especially upon treatment initiation. Concomitant antihypertensive medication
      increases the incidence of hypotension with some alpha-blockers. Use of alpha(1A)
      selective blockers, evening dosing and drug intake after a meal can reduce the
      risk of hypotension. IFIS can occur with all drugs exerting alpha(1)-adrenoceptor
      antagonist properties and has especially been reported for tamsulosin. It makes
      cataract surgery more challenging but does not constitute a health risk to
      patients. IFIS seems to result from inhibition of iris dilator muscle contraction
      and occurs in men or women, even after alpha-blockers have been discontinued. To
      reduce the risk of IFIS, the authors suggest taking a careful drug history,
      postponing alpha-blocker treatment for patients with scheduled cataract surgery
      and careful counseling of patients taking alpha-blockers.

PMID- 25073736
TI  - Impact of antiviral treatment on survival in HCV-positive liver recipients.
AB  - BACKGROUND: Sequels of chronic HCV infection are currently one of the most common
      indications for liver transplantation (LTx). Because HCV reinfection and
      allograft injury are inevitable, it may influence survival. Earlier studies have
      not reported higher mortality among HCV-infected patients, but cumulative data
      seem to contradict these findings. The aim of the study was to analyze post-LTx
      survival in HCV-positive patients in comparison with non-HCV-positive recipients
      and impact of antiviral treatment on survival in patients with recurrent HCV
      hepatitis. MATERIAL AND METHODS: Using data from the Polish national transplant
      registry, a retrospective cohort study of 327 patients who underwent LTx between
      2000 and 2012 was performed. Cumulative 5-year mortality for HCV-positive
      patients vs. HCV-negative recipients and HCV-positive recipients treated with
      pegylated interferon/ribavirin vs. non-treated subjects was calculated using
      Kaplan-Meyer methodology. Mortality hazard rates were estimated using univariate
      proportional Cox models. RESULTS: Liver transplantation in HCV-positive vs. HCV
      negative recipients was associated with significantly lower survival rate
      (cumulative 5-year survival 89.8 vs. 80.26%, respectively, p=0.04276) with a 5
      year mortality HR of 1.99. Antiviral treatment improved survival irrespective of
      virological response (84.06% treated vs. 51.22% non-treated, p=0.00003).
      Univariate Cox HR for HCV treated vs. untreated patients is 0.18. Further
      improvement of survival was significantly associated with sustained virological
      response (100% vs. 77.67%, p=0.042). CONCLUSIONS: Our study confirms higher
      mortality risk among HCV-infected transplant recipients, improved survival
      related to the HCV treatment following graft reinfection, and positive
      association between the HCV treatment success and better survival.

PMID- 25073737
TI  - Creation of a gated antibody as a conditionally functional synthetic protein.
AB  - The ability to conditionally direct antibodies is a potentially powerful
      application for Synthetic Biology in Medicine. Here we show that control of
      antibody binding through site-specific, chemical phosphorylation of a recognition
      domain creates a 'gated' antibody (Ab). This displays a crude Boolean logic where
      binding is induced in an enzyme-AND-antigen dependent manner. This 'AND-Ab' is
      therefore active only in the presence of two biomarker inputs: the simultaneous
      expression of a (cell surface) antigen and secreted enzyme to generate function
      in vitro, on cells and in mammalian tissue. Such gated Abs, either alone or in
      combination, could allow the application of logic strategies to enhance precision
      in biological interrogation, modulation and in therapy. 

PMID- 25073739
TI  - Copper-catalyzed azide-alkyne cycloaddition (click chemistry)-based detection of
      global pathogen-host AMPylation on self-assembled human protein microarrays.
AB  - AMPylation (adenylylation) is a recently discovered mechanism employed by
      infectious bacteria to regulate host cell signaling. However, despite significant
      effort, only a few host targets have been identified, limiting our understanding
      of how these pathogens exploit this mechanism to control host cells. Accordingly,
      we developed a novel nonradioactive AMPylation screening platform using high
      density cell-free protein microarrays displaying human proteins produced by human
      translational machinery. We screened 10,000 unique human proteins with Vibrio
      parahaemolyticus VopS and Histophilus somni IbpAFic2, and identified many new
      AMPylation substrates. Two of these, Rac2, and Rac3, were confirmed in vivo as
      bona fide substrates during infection with Vibrio parahaemolyticus. We also
      mapped the site of AMPylation of a non-GTPase substrate, LyGDI, to threonine 51,
      in a region regulated by Src kinase, and demonstrated that AMPylation prevented
      its phosphorylation by Src. Our results greatly expanded the repertoire of
      potential host substrates for bacterial AMPylators, determined their recognition
      motif, and revealed the first pathogen-host interaction AMPylation network. This
      approach can be extended to identify novel substrates of AMPylators with
      different domains or in different species and readily adapted for other post
      translational modifications. 

PMID- 25073740
TI  - Molecular architecture and function of the SEA complex, a modulator of the TORC1
      pathway.
AB  - The TORC1 signaling pathway plays a major role in the control of cell growth and
      response to stress. Here we demonstrate that the SEA complex physically interacts
      with TORC1 and is an important regulator of its activity. During nitrogen
      starvation, deletions of SEA complex components lead to Tor1 kinase
      delocalization, defects in autophagy, and vacuolar fragmentation. TORC1
      inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular
      levels of SEA complex members. We used affinity purification and chemical cross
      linking to generate the data for an integrative structure modeling approach,
      which produced a well-defined molecular architecture of the SEA complex and
      showed that the SEA complex comprises two regions that are structurally and
      functionally distinct. The SEA complex emerges as a platform that can coordinate
      both structural and enzymatic activities necessary for the effective functioning
      of the TORC1 pathway. 

PMID- 25073742
TI  - Prostate magnetic resonance imaging: challenges of implementation.
AB  - Prostate cancer is among the most common causes of cancer and cancer deaths in
      men. Screening methods and optimal treatments have become controversial in recent
      years. Prostate magnetic resonance imaging (MRI) is gaining popularity as a tool
      to assist diagnosis, risk assessment, and staging. However, implementation into
      clinical practice can be difficult, with many challenges associated with image
      acquisition, postprocessing, interpretation, reporting, and radiologic-pathologic
      correlation. Although state-of-the-art technology is available at select sites
      for targeting tissue biopsy and interpreting multiparametric prostate MRI, many
      institutions struggle with adapting this new technology into an efficient
      multidisciplinary model of patient care. This article reviews several of the
      challenges that radiologists should be aware of when integrating prostate MRI
      into their clinical practice. 

PMID- 25073743
TI  - Analysis of the role of DOP on the particulate phosphatase activity in Toulon Bay
      (N.W. Mediterranean Sea, France).
AB  - Alkaline phosphatase (AP) activity was studied on homogenates of particulate
      material in relation to the concentrations of AP-hydrolysable (DOPpa) and AP-non
      hydrolysable (DOPr) phosphorus. AP activity had high and low Km components. The
      high affinity activity came from ectoenzymes. It was negatively and significantly
      correlated with DOPr as with the sum of DIP and DOPr, but not with DOPpa. However
      negative correlations with DOPpa existed when DIP concentrations decreased.
      Significant correlations with the sum of DIP and DOPpa attest of additive effects
      of DIP and DOPpa. The low affinity activity came from "endoenzymes". This
      activity was also negatively correlated with DOP (DOPpa and DOPr). DOPpa and to a
      lesser extent DOPr influenced also positively the protein and/or Chlorophyll
      biomasses of the particulate material. We hypothesize that the correlations of
      the AP activity with DOP come from regenerated phosphate sequestered in cells and
      not released in the environment with DIP. 

PMID- 25073741
TI  - Suberoylanilide hydroxamic acid (SAHA)-induced dynamics of a human histone
      deacetylase protein interaction network.
AB  - Histone deacetylases (HDACs) are targets for cancer therapy. Suberoylanilide
      hydroxamic acid (SAHA) is an HDAC inhibitor approved by the U.S. Food and Drug
      Administration for the treatment of cutaneous T-cell lymphoma. To obtain a better
      mechanistic understanding of the Sin3/HDAC complex in cancer, we extended its
      protein-protein interaction network and identified a mutually exclusive pair
      within the complex. We then assessed the effects of SAHA on the disruption of the
      complex network through six homologous baits. SAHA perturbs multiple protein
      interactions and therefore compromises the composition of large parts of the
      Sin3/HDAC network. A comparison of the effect of SAHA treatment on gene
      expression in breast cancer cells to a knockdown of the ING2 subunit indicated
      that a portion of the anticancer effects of SAHA may be attributed to the
      disruption of ING2's association with the complex. Our dynamic protein
      interaction network resource provides novel insights into the molecular mechanism
      of SAHA action and demonstrates the potential for drugs to rewire networks. 

PMID- 25073744
TI  - Concerning "Hematological, immunological, and cardiovascular changes in
      individuals residing in a polluted city of India: a study in Delhi".

PMID- 25073745
TI  - Visual ability of patients seeking outpatient low vision services in the United
      States.
AB  - IMPORTANCE: Most patients with low vision are elderly and have functional
      limitations from other health problems that could add to the functional
      limitations caused by their visual impairments. OBJECTIVE: To identify factors
      that contribute to visual ability measures in patients who present for outpatient
      low vision rehabilitation (LVR) services. DESIGN, SETTING, AND PARTICIPANTS: As
      part of a prospective, observational study of new patients seeking outpatient
      LVR, 779 patients from 28 clinical centers in the United States were enrolled in
      the Low Vision Rehabilitation Outcomes Study (LVROS) from April 25, 2008, through
      May 2, 2011. The Activity Inventory (AI), an adaptive visual function
      questionnaire, was administered to measure overall visual ability and visual
      ability in 4 functional domains (reading, mobility, visual motor function, and
      visual information processing) at baseline before LVR. The Geriatric Depression
      Scale, Telephone Interview for Cognitive Status, and Medical Outcomes Study 36
      Item Short-Form Health Survey physical functioning questionnaires were also
      administered to measure patients' psychological, cognitive, and physical health
      states, respectively. MAIN OUTCOMES AND MEASURES: Predictors of visual ability
      and functional domains as measured by the AI. RESULTS: Among the 779 patients in
      the LVROS sample, the mean age was 76.4 years, 33% were male, and the median
      logMAR visual acuity score was 0.60 (0.40-0.90 interquartile range). Correlations
      were observed between logMAR visual acuity and baseline visual ability overall (r
      = -0.42) and for all functional domains. Visual acuity was the strongest
      predictor of visual ability (P  < .001) and reading ability (P < .001) and had a
      significant independent effect on the other functional domains. Physical ability
      was independently associated with (P < .001) overall visual ability as well as
      mobility and visual motor function. Depression had a consistent independent
      effect (P < .001) on overall visual ability and on all functional domains,
      whereas cognition had an effect on only reading and mobility (P < .001).
      CONCLUSIONS AND RELEVANCE: Visual ability is a multidimensional construct, with
      visual acuity, depression, physical ability, and cognition explaining more than
      one-third of the variance in visual ability as measured by the AI. The
      significant contributions of the nonvisual factors to visual ability measures and
      the rehabilitation potential (ie, ceiling) effects they may impose on LVR are
      important considerations when measuring baseline visual ability and ultimately
      LVR outcomes in ongoing clinical research.

PMID- 25073746
TI  - [Fibromyalgia patients' perceptions of the impact of the disease in the
      workplace].
AB  - OBJECTIVE: To explore the perceptions of patients with fibromyalgia (FM) on the
      problems they experience in the workplace, to discuss how they face and adapt to
      the limitations imposed by the symptoms of this disease. DESIGN: An exploratory
      qualitative study conducted in 2009. LOCATION: Associations of patients of FM
      from Valencia (Spain). PARTICIPANTS: Sixteen patients (13 women and 3 men)
      diagnosed with FM by a rheumatologist, of different ages and occupations,
      selected from key informants and the snowball technique. METHOD: Pragmatic
      sample. Semi-structured interviews until saturation of information when no new
      information emerged. Qualitative content analysis using the software Atlas.ti-5,
      to generate and assign codes, forming categories and identifying a latent theme.
      RESULTS: We identified four categories: difficulties in meeting the work demands,
      need for social support in the workplace, strategies adopted to continue working,
      and resistance to leave the employment. A theme which crosscut these categories
      emerged: FM patients motivation to continue in the labour market. CONCLUSIONS:
      Addressing the specific needs of patients it is essential in order to helping
      them to stay in the labour market, according to their capabilities. Awareness
      programs about the consequences of FM in the workplace are needed to achieve the
      collaboration of managers, entrepreneurs, occupational health professionals and
      primary care physicians and nurses.

PMID- 25073747
TI  - Fronto-ethmoidal osteoma. Open treatment.
AB  - INTRODUCTION: Osteoma is a benign tumour, composed of mature compact or
      cancellous bone, which can arise in any facial bone. Among the paranasal sinuses,
      the frontal and ethmoid sinuses are most frequently involved. Osteoma grows very
      slowly and small lesions are often not symptomatic. On the other hand, sometimes
      patients present with symptoms such as sinusitis, headache or ophtalmologic
      manifestations. These findings are secondary to obstruction of the involved sinus
      cavity with secondary mucocele formation or occasionally an expansile lesion with
      distortion of the facial contour. MATERIALS AND METHODS: From 2005 to 2010,
      twenty-one (21) patients affected with non-syndromic fronto-ethmoidalosteomas
      were evaluated in our Department. Collected data include patients' age at the
      time of disorders, gender, presenting signs and symptoms, primary diagnosis, type
      and characteristics of the treatment performed, radiological findings and post
      treatment results. All patients were investigated by CT scans in axial and
      coronal planes. The treatment and outcomes of this group were reviewed. RESULTS:
      All patients of the study underwent surgery and had a follow-up of at least 5
      years. Surgical excision of the tumour was undertaken. Postoperative CT scans in
      axial and coronal planes showed complete removal of the tumour in all cases. No
      complications or recurrences were observed. DISCUSSION: Small, asymptomatic
      osteomas probably do not need to be treated but should be observed periodically.
      Surgical management remains the mainstay of treatment for these tumours. It
      requires total excision via an adequate approach, depending upon the site of
      presentation. CONCLUSION: A purely endoscopic endonasal approach has the risk of
      incomplete excision. In our experience open technique provides a wide exposure
      and better control. Even frontal osteomas can be safely removed by careful open
      surgery KEY WORDS: Ethmoidal sinus, Frontal sinus, Open treatment, Osteoma,
      Paranasal sinuses.

PMID- 25073748
TI  - Use of wavelet coherence to assess two-joint coordination during quiet upright
      stance.
AB  - Joint coordination plays a critical role in maintaining postural stability, yet
      there is limited existing work describing joint coordination patterns in the time
      frequency domain. Here, two-joint coordination was examined during quiet upright
      stance. A wavelet coherence method was applied to quantify the coherence between
      ankle-trunk and ankle-head angles in the sagittal and frontal planes. Wavelet
      coherence results indicated intermittent joint coordination particularly for
      frequencies of 2.5-4.0Hz. Coherence results were further processed to estimate
      mean time intervals between coherence instances, coherence burst frequency, and
      the ratio of in-phase versus anti-phase behaviors. Time intervals between
      intermittent coherence were 1.3-1.5sec, coherence burst frequency was ~0.4Hz, and
      phase ratios were ~1.0. Intermittent "bursting" of postural muscles may account
      for the finding of intermittent coherence in the noted frequency band. Some age
      and/or gender differences in coherence were found, and may be related to
      comparable differences in postural control ability or strategies. Results from
      application of this new method support earlier evidence that kinematic
      coordination is achieved intermittently rather than continuously during quiet
      upright stance. This method may provide richer information regarding such
      coordination, and could be a useful approach in future studies. 

PMID- 25073749
TI  - Profile and predictors of service needs for families of children with autism
      spectrum disorders.
AB  - PURPOSE: Increasing demand for autism services is straining service systems.
      Tailoring services to best meet families' needs could improve their quality of
      life and decrease burden on the system. We explored overall, best, and worst met
      service needs, and predictors of those needs, for families of children with
      autism spectrum disorders. METHODS: Parents of 143 children with autism spectrum
      disorders (2-18 years) completed a survey including demographic and descriptive
      information, the Family Needs Survey-Revised, and an open-ended question about
      service needs. Descriptive statistics characterize the sample and determine the
      degree to which items were identified and met as needs. Predictors of total and
      unmet needs were modeled with regression or generalized linear model. Qualitative
      responses were thematically analyzed. RESULTS: The most frequently identified
      overall and unmet service needs were information on services, family support, and
      respite care. The funding and quality of professional support available were
      viewed positively. Decreased child's age and income and being an older mother
      predicted more total needs. Having an older child or mother, lower income, and
      disruptive behaviors predicted more total unmet needs, yet only disruptive
      behaviors predicted proportional unmet need. Child's language or intellectual
      abilities did not predict needs. CONCLUSION: Findings can help professionals,
      funders, and policy-makers tailor services to best meet families' needs.

PMID- 25073750
TI  - High self-perceived stress and poor coping in intellectually able adults with
      autism spectrum disorder.
AB  - Despite average intellectual capacity, autistic traits may complicate performance
      in many everyday situations, thus leading to stress. This study focuses on stress
      in everyday life in intellectually able adults with autism spectrum disorders. In
      total, 53 adults (25 with autism spectrum disorder and 28 typical adults from the
      general population) completed the Perceived Stress Scale. Autistic traits were
      assessed using the Autism Spectrum Quotient. Adults with autism spectrum disorder
      reported significantly higher subjective stress and poorer ability to cope with
      stress in everyday life, as compared to typical adults. Autistic traits were
      associated with both subjective stress/distress and coping in this cross
      sectional series. The long-term consequences of chronic stress in everyday life,
      as well as treatment intervention focusing on stress and coping, should be
      addressed in future research as well as in the clinical management of
      intellectually able adults with autism spectrum disorder. 

PMID- 25073751
TI  - Asymmetry of projected increases in extreme temperature distributions.
AB  - A statistical analysis reveals projections of consistently larger increases in
      the highest percentiles of summer and winter temperature maxima and minima versus
      the respective lowest percentiles, resulting in a wider range of temperature
      extremes in the future. These asymmetric changes in tail distributions of
      temperature appear robust when explored through 14 CMIP5 climate models and three
      reanalysis datasets. Asymmetry of projected increases in temperature extremes
      generalizes widely. Magnitude of the projected asymmetry depends significantly on
      region, season, land-ocean contrast, and climate model variability as well as
      whether the extremes of consideration are seasonal minima or maxima events. An
      assessment of potential physical mechanisms provides support for asymmetric tail
      increases and hence wider temperature extremes ranges, especially for northern
      winter extremes. These results offer statistically grounded perspectives on
      projected changes in the IPCC-recommended extremes indices relevant for impacts
      and adaptation studies. 

PMID- 25073752
TI  - A comparative study of three methods of ProSeal laryngeal mask airway insertion
      in children with simulated difficult laryngoscopy using a rigid neck collar.
AB  - BACKGROUND: Combined introducer tool and stylet technique of ProSeal laryngeal
      mask airway (PLMA) insertion was compared with the conventional digital
      manipulation and introducer tool technique in children with a rigid neck collar.
      METHODS: This was a randomized, single blinded, prospective study. Ninety ASA
      Grade I-II children weighing 10-20 kg were randomly allocated for PLMA insertion
      using the digital, introducer tool (IT) or combined IT and stylet techniques.
      Each group contained 30 patients. Difficult laryngoscopy was simulated using a
      rigid neck collar. The laryngoscopic view was graded prior to PLMA insertion. The
      digital and IT techniques were performed according to the manufacturer's
      instructions. The combined technique involved attaching the IT to the PLMA and
      inserting a flexible stylet through the drain tube. RESULTS: The median Cormack
      and Lehane grade was 2 in all three groups. Insertion was more frequently
      successful with the combined technique at the first attempt (combined 100%,
      digital 65.38%, IT 66.67%; p < 0.05), but success after three attempts was
      similar (combined 100%, digital 86.67%, IT 90%; p > 0.05). The time taken for
      successful placement was similar among groups at the first attempt, but was
      shorter for the combined technique for overall attempts (combined 18.33 +/- 1.27
      seconds, digital 27.85 +/- 9.05 seconds, IT 26.89 +/- 7.17 seconds; p < 0.05).
      There was no difference in postoperative airway morbidity. CONCLUSION: PLMA
      insertion with combined IT and stylet technique was more frequently successful
      than the digital or IT technique in pediatric patients without cervical spine
      motion.

PMID- 25073753
TI  - Unanticipated difficult nasotracheal extubation following oral surgery.
AB  - Difficult tracheal extubation is a rare but potentially dangerous problem that
      can be life threatening especially when it is unexpected and there is a lack of
      preparation. Most of these cases are associated with orofacial surgery. We herein
      present two patients with oral cavity cancer who experienced unexpected
      postoperative difficult nasotracheal extubation by a Kirschner pin penetrating
      the endotracheal tube and fixing the tube at the maxillary bone following tumor
      resection. The pins were found by fiberoptic bronchoscopy. Both patients were
      returned to the operating theater immediately for removal of the penetrating pins
      as well as the endotracheal tubes. The common causes of difficult tracheal
      extubation and strategies of managing these situations are discussed in the
      article. 

PMID- 25073754
TI  - The impact of nasal surgery on sleep quality: a prospective outcomes study.
AB  - OBJECTIVE: (1) Evaluate the impact of nasal airway surgery on sleep quality using
      validated outcome measurements, (2) compare the utility of Epworth Sleepiness
      Scale (ESS) versus Pittsburgh Sleep Quality Index (PSQI) as a reflection of sleep
      quality, and (3) identify perioperative variables that might correlate with a
      beneficial effect of nasal surgery on sleep quality. STUDY DESIGN: Prospective
      outcome study of patients with symptomatic nasal obstruction undergoing nasal
      airway surgery. SETTING: Academic medical center. METHODS: Patients completed the
      Nasal Obstruction Symptom Evaluation (NOSE) scale, ESS, PSQI, and Ease-of
      Breathing and Sleep Quality Likert scales preoperatively and 3 months
      postoperatively. A nonparametric analysis compared pre- and postoperative values,
      and associations were examined using Spearman correlations. RESULTS: Sixty-one
      patients completed the study. Mean NOSE scores decreased significantly from 68.2
      preoperatively to 17.5 three months after surgery. Mean ESS scores and PSQI
      scores improved (P < .0001) over that same interval (7.5 to 5.3 and 7.8 to 4.6,
      respectively). There was a correlation seen between the degree of change in both
      NOSE scores and Ease-of-Breathing scores and the change in sleep quality measured
      using the PSQI or Sleep Quality Likert scores. The PSQI correlated better with
      Sleep Quality Likert scores than the ESS. Overall, 86.9% of subjects reported
      subjective improvement in sleep quality postoperatively. CONCLUSION: In patients
      undergoing nasal airway surgery there may be a secondary improvement in
      subjective sleep quality. The degree of change in sleep quality correlates with
      the severity of nasal obstruction preoperatively and the degree of improvement in
      obstruction with surgery.

PMID- 25073755
TI  - A comparative study of different radiographic methods for detecting occlusal
      caries lesions.
AB  - OBJECTIVES: The aim of this in vitro study was to compare the diagnostic accuracy
      of different radiographic imaging modalities in detecting occlusal caries
      lesions. MATERIALS AND METHODS: Under standardized conditions, 125 extracted
      human permanent molar teeth with sound or occlusal caries lesions were
      radiographed using a conventional film system (F-speed), a direct digital imaging
      system (complementary metal oxide semiconductor sensor), an indirect digital
      imaging system (photostimulable phosphor plate) and a cone beam computed
      tomography system (CBCT). Two observers scored the resultant images for the
      presence or absence of caries. Then, the teeth were histologically prepared and a
      definite diagnosis was determined by stereomicroscopic assessment. The area under
      the receiver operating characteristic curve (Az), sensitivity, specificity and
      accuracy of each imaging modality were calculated, as well as the intra- and
      interexaminer reproducibility. RESULTS: For both thresholds, interexaminer
      agreement were higher for CBCT. For intraexaminer agreement, observers had
      different scores for both thresholds, but the scores were generally higher for
      CBCT. Similar Az values were achieved with all imaging methods at a diagnostic D1
      threshold. The Az values of the CBCT system were found to be statistically higher
      than those of the other imaging modalities at a diagnostic D3 threshold (p >
      0.05); no significant differences were found among the other imaging modalities.
      All radiographic methods showed similar sensitivities, specificities and accuracy
      in detecting D1 threshold. The CBCT system showed higher sensitivity and accuracy
      in detecting dentine lesions. CONCLUSIONS: Within the limitations of this study,
      CBCT exhibited better performance in detecting deep occlusal caries lesions than
      the other radiographic systems.

PMID- 25073757
TI  - Pistillate flower development and pollen tube growth mode during the delayed
      fertilization stage in Corylus heterophylla Fisch.
AB  - Unlike most angiosperms, in which fertilization occurs within several days after
      pollination, fertilization in hazel (Corylus Spp.) is delayed by two to three and
      a half months. However, the female inflorescences or young fruits are too hard or
      lignified to be dissected according to regular paraffin sectioning technique. So,
      what the nature of development during the extended progamic phases of hazel
      remains unknown. The female inflorescence development and pollen tube growth mode
      during the delayed fertilization stage in hazel were investigated by improved
      paraffin sectioning and aniline blue staining of pollen tubes. The results showed
      ovaries and ovules of hazel were invisible at the time of blooming. Early ovary
      and ovule primordium began to form from 15 to 20 days after blooming,
      respectively. Integument and mature embryo sacs differentiated from the nucellus
      on 40th and 55th day after blooming, respectively. Pollen tubes were retarded in
      the bottom of the style or the pollen tube cavity (PTC, a specifical lignified
      cavity structure at the bottom of style for pollen tube to rest during progamic
      phase) for about 26 days. Then, the pollen tubes were observed to leave the PTC
      and began to enter the ovary. After that, a single pollen tube passed through the
      vicinity of the micropyle. Finally, pollen tubes turned a corner and penetrated
      the embryo sac through the tissue of the chalaza instead of micropyle on 52 and
      55 days after blooming, respectively. The results of more in-depth information
      will be beneficial to better understanding of the delayed fertilization process
      in hazel. 

PMID- 25073758
TI  - In memoriam: Eveline Markiewicz.

PMID- 25073760
TI  - Evaluation of a direct 4D reconstruction method using generalised linear least
      squares for estimating nonlinear micro-parametric maps.
AB  - OBJECTIVE: Estimation of nonlinear micro-parameters is a computationally
      demanding and fairly challenging process, since it involves the use of rather
      slow iterative nonlinear fitting algorithms and it often results in very noisy
      voxel-wise parametric maps. Direct reconstruction algorithms can provide
      parametric maps with reduced variance, but usually the overall reconstruction is
      impractically time consuming with common nonlinear fitting algorithms. METHODS:
      In this work we employed a recently proposed direct parametric image
      reconstruction algorithm to estimate the parametric maps of all micro-parameters
      of a two-tissue compartment model, used to describe the kinetics of [[Formula:
      see text]F]FDG. The algorithm decouples the tomographic and the kinetic modelling
      problems, allowing the use of previously developed post-reconstruction methods,
      such as the generalised linear least squares (GLLS) algorithm. RESULTS: Results
      on both clinical and simulated data showed that the proposed direct
      reconstruction method provides considerable quantitative and qualitative
      improvements for all micro-parameters compared to the conventional post
      reconstruction fitting method. Additionally, region-wise comparison of all
      parametric maps against the well-established filtered back projection followed by
      post-reconstruction non-linear fitting, as well as the direct Patlak method,
      showed substantial quantitative agreement in all regions. CONCLUSIONS: The
      proposed direct parametric reconstruction algorithm is a promising approach
      towards the estimation of all individual microparameters of any compartment
      model. In addition, due to the linearised nature of the GLLS algorithm, the
      fitting step can be very efficiently implemented and, therefore, it does not
      considerably affect the overall reconstruction time.

PMID- 25073761
TI  - The NHS health check programme in England: a qualitative study.
AB  - Despite an extensive evidence-base linking patterns of health with social
      determinants, recent public health policy has emphasized 'lifestyle diseases' and
      risk factor modification through behavioural and pharmacological intervention. In
      England, one manifestation of this has been the launch of the National Health
      Service Health Check programme. This paper reports findings from a small-scale
      qualitative study exploring experiences of engaging with a community-based health
      check in Knowsley, England, among 17 males and 19 females, with varying levels of
      risk for cardiovascular disease, who agreed to be contacted for the purpose of
      research at the time they underwent their check. Analysis revealed that the
      community-based nature of the checks provided opportunities for people to find
      out more about their health who might not otherwise have done so. Participants
      expressed a range of responses to the communication of the risk score, often
      revealing their confusion about its meaning. Changes in behaviour were
      identified, which participants connected with having had a check. This study
      raises questions about where, how and by whom health checks are delivered.
      Emphasis on health checks reflects the dominant individualist ideology, but this
      study also suggests that the process provides opportunities to enable and empower
      individuals, albeit in small ways. However, they remain a 'downstream' approach
      to public health, emphasizing medical and behavioural options for risk factor
      reduction rather than focussing on primary prevention through changes to the
      wider environment. Furthermore, although developed as a central feature of the
      UK's strategy to reduce health inequalities, health checks may widen them. 

PMID- 25073762
TI  - Perceived impact of Ghana's conditional cash transfer on child health.
AB  - A plethora of studies from sub-Saharan Africa indicate that orphaned and
      vulnerable children are exposed to adverse health, education and other social
      outcomes. Across diverse settings, conditional cash transfer (CCT) programmes
      have been successful in improving health outcomes amongst vulnerable children.
      This study explored the pathways of CCTs' impact on the health of orphans and
      vulnerable children in rural Ghana. Due to the multi-dimensional nature of CCTs,
      the programme impact theory was used to conceptualize CCTs' pathways of impact on
      child health. A qualitative descriptive exploratory approach was used for this
      study. This study drew on the perspectives of 18 caregivers, 4 community leaders
      and 3 programme implementers from two rural districts in Ghana. Semi-structured
      individual interviews were conducted with the participants. Thematic content
      analysis was conducted on the interview transcripts to pull together core themes
      running through the entire data set. Five organizing themes emerged from the
      interview transcripts: improved child nutrition, health service utilization,
      poverty reduction and social transformation, improved education and improved
      emotional health and well-being demonstrating the pathways through which CCTs
      work to improve child health. The results indicated that CCTs offer a valuable
      social protection instrument for improving the health of orphans and vulnerable
      children by addressing the social determinants of child health such as nutrition,
      access to health care, child poverty and education. 

PMID- 25073763
TI  - Suffering and salutogenesis.
AB  - In considering pain and suffering, some considerations will appear about
      epistemological beliefs shaping the clinical practices of health-care workers.
      With this, we try to understand the usual omission of human suffering in the
      training of many health professionals. So, we emphasize the role of the
      pathogenic paradigm in how human suffering is viewed in health care. In contrast
      to those who see suffering only as pathogenic, we defend that suffering can be a
      source of significant learning for both the sufferer as well as those who
      undertake caring in certain circumstances. We therefore argue that it is
      necessary to educate for health and not only for illness, choosing a holistic
      paradigm: Aaron Antonovky's salutogenic model that encloses positive aspects of
      human suffering when it is lived with an internal sense of coherence.

PMID- 25073764
TI  - Adaptation in collaborative governance regimes.
AB  - Adaptation and the adaptive capacity of human and environmental systems have been
      of central concern to natural and social science scholars, many of whom
      characterize and promote the need for collaborative cross-boundary systems that
      are seen as flexible and adaptive by definition. Researchers who study
      collaborative governance systems in the public administration, planning and
      policy literature have paid less attention to adaptive capacity specifically and
      institutional adaptation in general. This paper bridges the two literatures and
      finds four common dimensions of capacity, including structural arrangements,
      leadership, knowledge and learning, and resources. In this paper, we focus on
      institutional adaptation in the context of collaborative governance regimes and
      try to clarify and distinguish collaborative capacity from adaptive capacity and
      their contributions to adaptive action. We posit further that collaborative
      capacities generate associated adaptive capacities thereby enabling institutional
      adaptation within collaborative governance regimes. We develop these distinctions
      and linkages between collaborative and adaptive capacities with the help of an
      illustrative case study in watershed management within the National Estuary
      Program. 

PMID- 25073765
TI  - Relationship between pastoralists' evaluation of rangeland state and vegetation
      threshold changes in Mongolian rangelands.
AB  - Applying the threshold concept to rangeland management is an important challenge
      in semi-arid and arid regions. Threshold recognition and prediction is necessary
      to enable local pastoralists to prevent the occurrence of an undesirable state
      that would result from unsustainable grazing pressure, but this requires a better
      understanding of the pastoralists' perception of vegetation threshold changes. We
      estimated plant species cover in survey plots along grazing gradients in steppe
      and desert-steppe areas of Mongolia. We also conducted interviews with local
      pastoralists and asked them to evaluate whether the plots were suitable for
      grazing. Floristic composition changed nonlinearly along the grazing gradient in
      both the desert-steppe and steppe areas. Pastoralists observed the floristic
      composition changes along the grazing gradients, but their evaluations of grazing
      suitability did not always decrease along the grazing gradients, both of which
      included areas in a post-threshold state. These results indicated that local
      pastoralists and scientists may have different perceptions of vegetation states,
      even though both of groups used plant species and coverage as indicators in their
      evaluations. Therefore, in future studies of rangeland management, researchers
      and pastoralists should exchange their knowledge and perceptions to successfully
      apply the threshold concept to rangeland management. 

PMID- 25073766
TI  - An in-depth examination of farmers' perceptions of targeting conservation
      practices.
AB  - Watershed managers have largely embraced targeting of agricultural conservation
      as a way to manage strategically non-point source pollution from agricultural
      lands. However, while targeting of particular watersheds is not uncommon,
      targeting farms and fields within a specific watershed has lagged. In this work,
      we employed a qualitative approach, using farmer interviews in west-central
      Indiana to better understand their views on targeting. Interviews focused on
      adoption of conservation practices on farmers' lands and identified their views
      on targeting, disproportionality, and monetary incentives. Results show
      consistent support for the targeting approach, despite dramatic differences in
      farmers' views of land stewardship, in their views about disproportionality of
      water quality impacts, and in their trust in conservation programming. While the
      theoretical concept of targeting was palatable to all participants, many raised
      concerns about its practical implementation, pointing to the need for flexibility
      when applying targeting solutions and revealing misgivings about the government
      agencies that perform targeting. 

PMID- 25073767
TI  - Being Thankful: Examining the Relationship Between Young Adult Religiosity and
      Gratitude.
AB  - Studies show that religious people tend to be more grateful, yet existing
      research tends to rely on small, non-representative samples and limited measures
      of religiosity. Therefore, we use a national sample (the National Study of Youth
      and Religion) and multiple measures of religiosity to examine the extent to which
      religion is associated with feelings of gratitude. We find that religious
      efficacy and having religious friends positively predict the extent to which
      young adults feel grateful. In contrast, religious affiliation, participation in
      organized religion, private devotion, religious salience, otherworldly beliefs,
      and being spiritual but not religious are unrelated to experiencing feelings of
      gratitude. 

PMID- 25073768
TI  - Exfoliated layered copper phosphonate showing enhanced adsorption capability
      towards Pb ions.
AB  - Copper 5-(2-bromothienyl)phosphonate (1) with a layered structure is obtained via
      solvothermal reaction. The layers can be successfully exfoliated using a "top
      down" approach, resulting in 2D nanosheets. The exfoliated sample shows an
      enhanced adsorption capability to the Pb(II) ions in aqueous solution compared
      with that of the bulk material.

PMID- 25073769
TI  - Source tracking of an anthrax outbreak in northeastern China using complete
      genome analysis and MLVA genotyping.
AB  - Anthrax is caused by Bacillus anthracis, an etiological agent behind zoonotic
      diseases worldwide. B. anthracis is also one of the most dangerous bioterrorism
      agents. An anthrax outbreak took place in Liaoning Province in northeastern China
      in August 2012. It resulted in seven human infections and dozens of dead cows.
      One B. anthracis strain, named Han, was isolated from a dead cow. This strain
      showed minor pathogenicity in mice and was suspected to be derived from the
      locally administered vaccine strain, Vac. In order to determine if the Han
      isolate was derived from the vaccine strain Vac and to track the source of the
      anthrax outbreak and, so, exclude the possibility of terrorism attack, a complete
      genome sequencing of these two B. anthracis strains was conducted. With the
      genome sequencing data, canonical single nucleotide polymorphism (SNP) analysis
      and whole-genome SNP screening were performed. The results indicate that the Han
      strain was markedly different from the Vac strain. Further analysis by multiple
      locus variable-number tandem repeat analysis (MLVA) showed that Han clustered
      with previously reported Chinese strains. The result of MLVA15 confirmed that the
      Han strain is a naturally occurring isolate instead of an engineered agent
      deliberately distributed by terrorists or other parties. In conclusion, our
      method used in this study not only facilitates epidemiological studies but also
      made it easier to distinguish naturally occurring outbreaks from intentionally
      released pathogens. 

PMID- 25073770
TI  - Incidence and factors predicting whooping cough due to parapertussis diagnosis
      among patients referred to general practitioners, Poland, 2009-2011.
AB  - Parapertussis leads to similar symptoms as pertussis, both being caused by
      bacteria from the genus Bordetella. Poland does not routinely diagnose nor
      conduct surveillance for parapertussis. We estimated parapertussis incidence and
      determined predictors of parapertussis diagnosis in the Polish population.
      Between July 2009 and April 2011, we conducted a prospective cohort study among
      patients attending 78 general practices. We included patients aged >= 3 years,
      with cough lasting >2 weeks, interviewed patients and collected a nasopharyngeal
      swab. We confirmed cases by real-time PCR. We estimated parapertussis incidence
      rates by dividing the number of cases by the summed person-time of observation in
      respective practices. We assessed predictors of PCR-confirmed parapertussis by
      comparing cases with patients testing negative. Using logistic regression, we
      calculated odds ratios (ORs) and 95% confidence intervals (95%CI). We identified
      78 cases among 1,231 patients meeting inclusion criteria. The incidence rate was
      39/100,000 person-years (95%CI 31-49). The highest rates (140/100,000; 95%CI 74
      239), were among children 3-5 years of age and the lowest (24/100,000; 95%CI 13
      40) among persons aged 20-39 years of age. Boys aged 3-5 years (7.1; 2.1-25.3)
      and women aged >40 years (4.1; 1.4-11.7) or living in crowded households (4.3;
      1.4-12.9) or contacting persons with prolonged cough (2.3; 1.1-4.5) were more
      likely to be diagnosed. Our results suggest that laboratory diagnosis could be
      prioritized for children in the preschool age and women aged over 40 who were
      referred to their GP with prolonged cough. In the absence of vaccine, post
      exposure prophylaxis for close contacts of parapertussis cases could an adequate
      preventative measure.

PMID- 25073771
TI  - Evaluation of two commercially available rapid diagnostic tests for Lyme
      borreliosis.
AB  - The diagnosis of Lyme disease is very complicated and a single diagnostic method
      cannot exclude infection. We assessed the performance of two commercially
      available Borrelia burgdorferi rapid diagnostic tests (RDT) in comparison to
      multiple laboratory-based diagnostic assays using specimens with a gradually
      increasing probability of Borrelia infection. Based on 200 specimens, the
      analytical sensitivities for IgG and IgM were 18 and 23% for the Lyme RDT and 24
      and 32% for the Borreliose Complete RDT. The sensitivity for detecting diagnosed
      Lyme borreliosis cases was low (26% Lyme RDT and 32% with the Borreliose Complete
      RDT respectively), whereas the specificity was good (85% Lyme RDT and 88%
      Borreliose Complete). Based on this evaluation, the performance of RDTs in
      detecting Lyme borreliosis appeared to be below that of laboratory-based
      diagnostics.

PMID- 25073772
TI  - Implications of 21st century science for nursing care: interpretations and
      issues.
AB  - The organizing theme for this special volume raises a momentous question: What
      are the implications of 21st century science for nursing care? The two terms the
      question relates - 21st century science and nursing care - are each of central
      importance for nursing and in philosophical enquiry about nursing as a practice,
      profession, or institution. These key terms are also highly charged and open to
      interpretation, as is the relationship of implication between them. Different
      interpretations or assumptions will steer the search for an answer in quite
      different directions. Putting the expectation of an answer in abeyance, this
      paper probes the question precisely in its openness to interpretation and
      contestation. In elaborating different ways in which the main terms of the
      question can be taken, and analysing how different interpretations of or
      assumptions about them lead to different responses, the paper delineates crucial
      issues and divisions in nursing and commentary about nursing today. 

PMID- 25073773
TI  - Robotic Roux-en-Y gastric bypass surgical simulation curriculum.

PMID- 25073774
TI  - Fasciculations in human hereditary disease.
AB  - Fasciculations are a manifestation of peripheral nerve hyperexcitability in
      addition to myokymia, neuromyotonia, cramps, or tetany. Fasciculations occur in
      hereditary and non-hereditary diseases. Among the hereditary diseases,
      fasciculations are most frequently reported in familial amyotrophic lateral
      sclerosis (FALS), and spinal muscular atrophy (SMA). Among the non-hereditary
      diseases, fasciculations occur most frequently in peripheral nerve
      hyperexcitability syndromes (Isaac's syndrome, voltage-gated potassium
      channelopathy, cramp fasciculation syndrome, Morvan syndrome). If the cause of
      fasciculations remains unknown, they are called benign. Systematically reviewing
      the literature about fasciculations in hereditary disease shows that
      fasciculations can be a phenotypic feature in bulbospinal muscular atrophy
      (BSMA), GM2-gangliosidosis, triple-A syndrome, or hereditary neuropathy.
      Additionally, fasciculations have been reported in familial amyloidosis,
      spinocerebellar ataxias, Huntington's disease, Rett syndrome, central nervous
      system disease due to L1-cell adhesion molecule (L1CAM) mutations, Fabry's
      disease, or Gerstmann-Straussler disease. Rarely, fasciculations may be a
      phenotypic feature in patients with mitochondrial disorders or other myopathies.
      Fasciculations are part of the phenotype in much more genetic disorders than
      commonly assumed. Fasciculations not only occur in motor neuron disease, but also
      in hereditary neuropathy, spinocerebellar ataxia, GM2-gangliosidosis,
      Huntington's disease, Rett syndrome, Fabry's disease, Gerstmann-Straussler
      disease, mitochondrial disorders, or muscular dystrophies.

PMID- 25073775
TI  - A quantitative evaluation of damage in normal appearing white matter in patients
      with multiple sclerosis using diffusion tensor MR imaging at 3 T.
AB  - The white matter (WM) of the brain is damaged in multiple sclerosis (MS), even in
      areas that appear normal on standard MR imaging. The purpose of our study is to
      evaluate the damage of normal appearing white matter (NAWM) in patients with MS.
      In our study, 84 MS patients and 42 healthy adults underwent a routine brain MRI,
      including also diffusion tensor imaging (DTI). All studies were performed on a 3
      T MRI scanner. Fractional anisotropy (FA) and apparent diffusion coefficient
      (ADC) values were obtained. The DTI parameters of NAWM were correlated with
      expanded disability status scales (EDSS) scores. Our results showed statistically
      significant differences in FA and ADC values between MS plaques and the
      symmetrical NAWM, as also between NAWM and the respective white matter in
      controls. The ADC values of the NAWM correlated with the EDSS scores. The present
      study demonstrated damage of the NAWM in MS patients, using DTI in 3.0 T. DTI may
      be used in the detection of subtle damage of the white matter.

PMID- 25073776
TI  - Atrial myxoma presenting with multiple intracranial fusiform aneurysms: a case
      report.

PMID- 25073777
TI  - Breast implant-associated anaplastic large cell lymphoma: sensitivity,
      specificity, and findings of imaging studies in 44 patients.
AB  - Breast implant-associated anaplastic large cell lymphoma (BIA ALCL) is a newly
      described clinicopathologic entity. The purpose of this study is to describe the
      imaging findings of patients with BIA ALCL and determine their sensitivity and
      specificity in the detection of the presence of an effusion or a mass related to
      BIA ALCL. A retrospective search was performed of our files as well as of the
      world literature for patients with pathologically proven BIA ALCL who had been
      assessed by any imaging study including ultrasound (US), computerized tomography
      (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT,
      as well as mammography. The sensitivity and specificity of each imaging modality
      in the detection of an effusion or a mass around breast implants was determined.
      We identified 44 patients who had BIA ALCL and imaging studies performed between
      1997 and 2013. The sensitivity for detecting an effusion was 84, 55, 82, and 38
      %, and for detecting a mass was 46, 50, 50, and 64 %, by US, CT, MRI, and PET,
      respectively. The sensitivity of mammography in the detection of an abnormality
      without distinction of effusion or mass was 73 %, and specificity 50 %.
      Progression-free survival was worse in patients with an implant-associated mass
      (p = 0.001). CONCLUSIONS: Current imaging with US, CT, MR, and PET appears
      suboptimal in the detection of an imaging abnormality associated with BIA ALCL.
      This under diagnosis may reflect a lack of awareness of this rare entity
      suggesting the need for better understanding of the spectrum of imaging findings
      associated with BIA ALCL by breast imagers.

PMID- 25073778
TI  - Intracavitary physiotherapy is not inferior to endometrial scratching in patients
      with recurrent implantation failure.
AB  - PURPOSE: To investigate whether intracavitary physiotherapy is superior to
      endometrial scratching in patients with recurrent implantation failure (RIF)
      after in vitro fertilization/intracytoplasmic sperm injection- embryo transfer
      (IVF/ICSI-ET) cycles. METHODS: According to the inclusion criteria defined by our
      hospital, 63 patients with RIF were included in the retrospective study. 20
      patients who received intracavitary physiotherapy were classified into Group A, 8
      patients with both intracavitary physiotherapy and endometrial scratching were
      into Group B, and 35 patients who underwent endometrial scratching were into
      Group C. The primary outcome measures were implantation and clinical pregnancy
      rates. The secondary outcome measure was pregnancy outcome. RESULTS: There were
      no statistical differences in implantation and clinical pregnancy rates between
      Groups A and C (29.41 vs 35.59 %, 45.00 vs 48.57 % respectively, P > 0.05),
      Groups B and C (36.36 vs 35.59 %, 50.00 vs 48.57 % respectively, P > 0.05). In
      addition, no statistical differences were discovered in pregnancy outcomes
      between Groups A and C (P > 0.05), Groups B and C (P > 0.05). CONCLUSIONS:
      Intracavitary physiotherapy is not inferior to endometrial scratching on
      improving implantation and clinical pregnancy rates in patients with RIF after
      IVF/ICSI cycles.

PMID- 25073779
TI  - Comment on Tae-Hee Kim et al.: Genetic alteration in ovarian cancer.

PMID- 25073780
TI  - Retrospective analysis of the diagnostic yield of newborn drug testing.
AB  - BACKGROUND: The objective of this study was to identify high-yield screening risk
      factors for detecting maternal non-medical drug use during pregnancy. METHODS: A
      four year retrospective analysis was conducted at an academic medical center.
      Detailed chart review of both the newborn and mother's medical record was
      performed on all cases for which one or more drug(s) or metabolite(s) were
      identified and confirmed in meconium or urine. RESULTS: 229 (9.2%) of 2,497
      meconium samples out of 7,749 live births confirmed positive for one or more non
      medical drugs. History of maternal non-medical drug and/or tobacco use in
      pregnancy was present in 90.8% of non-medical drug use cases. Addition of social
      risk factors and inadequate prenatal care increased the yield to 96.9%.
      CONCLUSIONS: Use of focused screening criteria based on specific maternal and
      social risk factors may detect many prenatal non-medical drug exposures.

PMID- 25073781
TI  - Complications after oncologic scalp reconstruction: a 139-patient series and
      treatment algorithm.
AB  - OBJECTIVES/HYPOTHESIS: Evaluate the factors influencing choice of technique and
      complications of scalp reconstruction after oncologic ablation. STUDY DESIGN: A
      single-institution retrospective review of 139 patients requiring oncologic scalp
      resection with subsequent reconstruction from 1992 to 2010 was completed.
      METHODS: The type of reconstruction used and complications encountered
      postoperatively were recorded over a mean follow-up of 2.4 years. chi(2) and
      Fisher exact tests were used to compare complication rates based on defect
      characteristics, type of reconstruction, and patient demographics and
      comorbidities. RESULTS: Defect widths ranged from 0.7 to 35 cm of varying depths.
      Closure methods ranged from partial closure with granulation to free tissue
      transfer. The overall complication rate was 10.8%. Complication rates were higher
      when dealing with larger defect sizes (P = .016), deeper defects (P = .004), in
      patients who received preoperative radiation (P = .026), and in patients who were
      immunosuppressed (P = .026). CONCLUSIONS: Scalp defects encountered after
      oncologic resection can be a challenging reconstruction. The defect location,
      size, depth, and unique patient factors likely to affect wound healing should all
      be considered when choosing between reconstructive options. Larger and deeper
      defects and patient factors, such as preoperative radiation and
      immunosuppression, are more prone to wound complications and may require more
      advanced reconstructive techniques such as pedicled locoregional flaps or free
      tissue transfer. An algorithm for scalp reconstruction based on these principles
      is provided.

PMID- 25073782
TI  - Fruit and vegetable consumption and mortality from all causes, cardiovascular
      disease, and cancer: systematic review and dose-response meta-analysis of
      prospective cohort studies.
AB  - OBJECTIVE: To examine and quantify the potential dose-response relation between
      fruit and vegetable consumption and risk of all cause, cardiovascular, and cancer
      mortality. DATA SOURCES: Medline, Embase, and the Cochrane library searched up to
      30 August 2013 without language restrictions. Reference lists of retrieved
      articles. STUDY SELECTION: Prospective cohort studies that reported risk
      estimates for all cause, cardiovascular, and cancer mortality by levels of fruit
      and vegetable consumption. DATA SYNTHESIS: Random effects models were used to
      calculate pooled hazard ratios and 95% confidence intervals and to incorporate
      variation between studies. The linear and non-linear dose-response relations were
      evaluated with data from categories of fruit and vegetable consumption in each
      study. RESULTS: Sixteen prospective cohort studies were eligible in this meta
      analysis. During follow-up periods ranging from 4.6 to 26 years there were 56,423
      deaths (11,512 from cardiovascular disease and 16,817 from cancer) among 833,234
      participants. Higher consumption of fruit and vegetables was significantly
      associated with a lower risk of all cause mortality. Pooled hazard ratios of all
      cause mortality were 0.95 (95% confidence interval 0.92 to 0.98) for an increment
      of one serving a day of fruit and vegetables (P=0.001), 0.94 (0.90 to 0.98) for
      fruit (P=0.002), and 0.95 (0.92 to 0.99) for vegetables (P=0.006). There was a
      threshold around five servings of fruit and vegetables a day, after which the
      risk of all cause mortality did not reduce further. A significant inverse
      association was observed for cardiovascular mortality (hazard ratio for each
      additional serving a day of fruit and vegetables 0.96, 95% confidence interval
      0.92 to 0.99), while higher consumption of fruit and vegetables was not
      appreciably associated with risk of cancer mortality. CONCLUSIONS: This meta
      analysis provides further evidence that a higher consumption of fruit and
      vegetables is associated with a lower risk of all cause mortality, particularly
      cardiovascular mortality.

PMID- 25073784
TI  - HPV vaccination.

PMID- 25073783
TI  - Population red blood cell folate concentrations for prevention of neural tube
      defects: Bayesian model.
AB  - OBJECTIVE: To determine an optimal population red blood cell (RBC) folate
      concentration for the prevention of neural tube birth defects. DESIGN: Bayesian
      model. SETTING: Data from two population based studies in China. PARTICIPANTS:
      247,831 participants in a prospective community intervention project in China
      (1993-95) to prevent neural tube defects with 400 MUg/day folic acid
      supplementation and 1194 participants in a population based randomized trial
      (2003-05) to evaluate the effect of folic acid supplementation on blood folate
      concentration among Chinese women of reproductive age. INTERVENTION: Folic acid
      supplementation (400 MUg/day). MAIN OUTCOME MEASURES: Estimated RBC folate
      concentration at time of neural tube closure (day 28 of gestation) and risk of
      neural tube defects. RESULTS: Risk of neural tube defects was high at the lowest
      estimated RBC folate concentrations (for example, 25.4 (95% uncertainty interval
      20.8 to 31.2) neural tube defects per 10,000 births at 500 nmol/L) and decreased
      as estimated RBC folate concentration increased. Risk of neural tube defects was
      substantially attenuated at estimated RBC folate concentrations above about 1000
      nmol/L (for example, 6 neural tube defects per 10,000 births at 1180 (1050 to
      1340) nmol/L). The modeled dose-response relation was consistent with the
      existing literature. In addition, neural tube defect risk estimates developed
      using the proposed model and population level RBC information were consistent
      with the prevalence of neural tube defects in the US population before and after
      food fortification with folic acid. CONCLUSIONS: A threshold for "optimal"
      population RBC folate concentration for the prevention of neural tube defects
      could be defined (for example, approximately 1000 nmol/L). Population based RBC
      folate concentrations, as a biomarker for risk of neural tube defects, can be
      used to facilitate evaluation of prevention programs as well as to identify
      subpopulations at elevated risk for a neural tube defect affected pregnancy due
      to folate insufficiency.

PMID- 25073785
TI  - Folate and prevention of neural tube defects.

PMID- 25073786
TI  - Vaccinate boys as well as girls against HPV: it works, and it may be cost
      effective.

PMID- 25073787
TI  - The ageing males' symptoms scale for Chinese men: reliability,validation and
      applicability of the Chinese version.
AB  - In this study, the ageing males' symptoms (AMS) scale was translated into Chinese
      following methodological recommendations for linguistic and cultural adaptation.
      This study aimed to confirm the reliability, validation and applicability of the
      simplified Chinese version of the scale (CN-AMS) in older Chinese men, a free
      health screening for men older than 40 years was conducted. All participants
      completed a health questionnaire, which consisted of personal health information,
      AMS scale, the generic quality of life (QoL) instrument SF36 and the Beck
      Depression Inventory (BDI). The fasting blood samples of participants were
      collected on the day of completing the health questionnaire. Serum total
      testosterone (TT), albumin and sex hormone-binding globulin levels were measured
      and the level of free testosterone was calculated (calculated free testosterone,
      CFT). A total of 244 men (mean age: 52 +/- 7.3 years, range: 40-79 years) were
      involved in the investigation and provided informed consent before their
      participation. The reliability of CN-AMS was analysed as internal consistency
      reliability (Cronbach's alpha was 0.91) as well as a 4-week-interval test-retest
      stability (Pearson's correlation was 0.83) and found to be good. The validation
      of CN-AMS was analysed as the internal structure analysis (Pearson's correlation
      between total score and each item score r = 0.48-0.75), total-domain-correlation
      (among the three domains r = 0.47-0.68, p < 0.01; domains with the total score r
      = 0.81-0.88, p < 0.01), and cross-validation with other scales (with SF36 r = 
      0.59, p < 0.01; with BDI r = 0.50, p < 0.01). Androgen deficiency (AD) was
      defined as the presence of three sexual symptoms (decreased frequency of morning
      erections, sexual thoughts and erectile dysfunction) in combination with TT < 11
      nmol/L and CFT < 220 pmol/L, and the sensitivity and specificity for CN-AMS was
      68.8 and 6.8% respectively. The CN-AMS had sufficient sensitivity in screening AD
      of older men, but the low specificity made it unsuitable to be adopted as the
      diagnostic criteria. The scanning capability of AMS scale for AD has the downward
      trend with ageing and a hypothesis is proposed to give a possible reason for the
      new finding. 

PMID- 25073788
TI  - A multicentre pilot study investigating high-definition optical coherence
      tomography in the differentiation of cutaneous melanoma and melanocytic naevi.
AB  - BACKGROUND: High-definition optical coherence tomography scanners have recently
      been developed. OBJECTIVES: To assess the diagnostic performance of HD-OCT in the
      differentiation of benign melanocytic skin lesions (MSL) and cutaneous melanoma
      (CM). METHODS: Patients with MSL were assessed by HD-OCT. All diagnoses were
      histopathologically confirmed. One blinded observer evaluated both slice and en
      face HD-OCT images and diagnosed MLS on the basis of an algorithm adopted from
      reflectance confocal microscopy, recent HD-OCT reports, and conventional OCT.
      RESULTS: A total of 93 MSL were studied comprising 66 benign MSL and 27 CM. The
      sensitivity of HD-OCT was 74.1% [95% confidence interval (CI) 53.7-88.8%)],
      specificity was 92.4% (95% CI 83.2-97.5%). The positive predictive value was 80%,
      the negative predictive value 89.7%. The performance of HD-OCT depended on tumour
      thickness and the presence of borderline lesions indicated by high false negative
      rates in very thin melanomas and high false positive rates in dysplastic naevi.
      CONCLUSIONS: In the distinction of MSL, HD-OCT applied in an investigator blinded
      fashion has a moderate diagnostic performance. The diagnostic performance of HD
      OCT of MSL should be reassessed in other clinical settings.

PMID- 25073789
TI  - Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORgammat
      induction as downstream targets of Stat3.
AB  - Stat3 signaling is essential for the induction of RORgammat and subsequent Th17
      cell differentiation. However, the downstream targets of Stat3 for RORgammat
      expression remain largely unknown. We show here that a novel isoform of Sox5,
      named Sox5t, is induced in Th17 cells in a Stat3-dependent manner. In vivo, T
      cell-specific Sox5-deficient mice exhibit impaired Th17 cell differentiation and
      are resistant to experimental autoimmune encephalomyelitis and delayed-type
      hypersensitivity. Retrovirus-mediated induction of Sox5 together with c-Maf
      induces Th17 cell differentiation even in Stat3-deficient CD4(+) T cells but not
      in RORgammat-deficient CD4(+) T cells, indicating that Sox5 and c-Maf induce Th17
      cell differentiation as downstream effectors of Stat3 and as upstream inducers of
      RORgammat. Moreover, Sox5 physically associates with c-Maf via the HMG domain of
      Sox5 and DNA-binding domain of c-Maf, and Sox5 together with c-Maf directly
      activates the promoter of RORgammat in CD4(+) T cells. Collectively, our results
      suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via
      the induction of RORgammat as downstream targets of Stat3.

PMID- 25073790
TI  - Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of
      inflammatory brain disease.
AB  - Amyloid fibrils composed of peptides as short as six amino acids are effective
      therapeutics for experimental autoimmune encephalomyelitis (EAE).
      Immunosuppression arises from at least two pathways: (1) expression of type 1 IFN
      by pDCs, which were induced by neutrophil extracellular traps arising from the
      endocytosis of the fibrils; and (2) the reduced expression of IFN-gamma, TNF, and
      IL-6. The two independent pathways stimulated by the fibrils can act in concert
      to be immunosuppressive in Th1 indications, or in opposition, resulting in
      inflammation when Th17 T lymphocytes are predominant. The generation of type 1
      IFN can be minimized by using polar, nonionizable, amyloidogenic peptides, which
      are effective in both Th1 and Th17 polarized EAE. 

PMID- 25073791
TI  - Targeting PI3Kgamma activity decreases vascular trauma-induced intimal
      hyperplasia through modulation of the Th1 response.
AB  - Interventional strategies to treat atherosclerosis, such as transluminal
      angioplasty and stent implantation, often cause vascular injury. This leads to
      intimal hyperplasia (IH) formation that induces inflammatory and
      fibroproliferative processes and ultimately restenosis. We show that
      phosphoinositide 3-kinase gamma (PI3Kgamma) is a key player in IH formation and
      is a valid therapeutic target in its prevention/treatment. PI3Kgamma-deficient
      mice and mice expressing catalytically inactive PI3Kgamma (PI3Kgamma KD) showed
      reduced arterial occlusion and accumulation of monocytes and T cells around sites
      of vascular lesion. The transfer of PI3Kgamma KD CD4(+) T cells into Rag2
      deficient mice greatly reduced vascular occlusion compared with WT cells, clearly
      demonstrating the involvement of PI3Kgamma in CD4(+) T cells during IH formation.
      In addition we found that IH is associated with increased levels of Th1 and Th17
      cytokines. A specific decrease in the Th1 response was observed in the absence of
      PI3Kgamma activity, leading to decreased CXCL10 and RANTES production by smooth
      muscle cells. Finally, we show that treatment with the PI3Kgamma inhibitor AS
      605240 is sufficient to decrease IH in both mouse and rat models, reinforcing the
      therapeutic potential of PI3Kgamma inhibition. Altogether, these findings
      demonstrate a new role for PI3Kgamma activity in Th1-controlled IH development.

PMID- 25073794
TI  - RSC Chromatography Monographs Quantitative In Silico Chromatography Computational
      Modelling of Molecular Interactions.
AB  - All early chromatographic techniques, starting from the primitive "ancient"
      chromatography introduced by Tswett in the very early twentieth century,
      perfected in partition chromatography in the 1940s by Martin and Synge, and
      extended to a variety of additional separation mechanisms later, were first
      entirely experimental trial-and-error methods. The early years can also be
      characterized by searching for theoretical base of various separation techniques
      that would allow establishing relation between the structure of the analytes and
      their chromatographic behavior. The advent of computers followed by development
      of the new software then revolutionized the theoretical approaches and enabled
      detailed modeling instead of tedious experimentation. This book introduces the
      readers to the era of computational modeling in which molecular interactions are
      used to analyze the mechanisms of general molecular interactions with a special
      focus on biological applications. This article is protected by copyright. All
      rights reserved.

PMID- 25073793
TI  - The CONSTANS-like 4 transcription factor, AtCOL4, positively regulates abiotic
      stress tolerance through an abscisic acid-dependent manner in Arabidopsis.
AB  - The precise roles of the B-box zinc finger family of transcription factors in
      plant stress are poorly understood. Functional analysis was performed on AtCOL4,
      an Arabidopsis thaliana L. CONSTANS-like 4 protein that is a putative novel
      transcription factor, and which contains a predicted transcriptional activation
      domain. Analyses of an AtCOL4 promoter-beta-glucuronidase (GUS) construct
      revealed substantial GUS activity in whole seedlings. The expression of AtCOL4
      was strongly induced by abscisic acid (ABA), salt, and osmotic stress. Mutation
      in atcol4 resulted in increased sensitivity to ABA and salt stress during seed
      germination and the cotyledon greening process. In contrast, AtCOL4
      overexpressing plants were less sensitive to ABA and salt stress compared to the
      wild type. Interestingly, in the presence of ABA or salt stress, the transcript
      levels of other ABA biosynthesis and stress-related genes were enhanced induction
      in AtCOL4-overexpressing and WT plants, rather than in the atcol4 mutant. Thus,
      AtCOL4 is involved in ABA and salt stress response through the ABA-dependent
      signaling pathway. Taken together, these findings provide compelling evidence
      that AtCOL4 is an important regulator for plant tolerance to abiotic stress. 

PMID- 25073792
TI  - Role of Blimp-1 in programing Th effector cells into IL-10 producers.
AB  - Secretion of the immunosuppressive cytokine interleukin (IL) 10 by effector T
      cells is an essential mechanism of self-limitation during infection. However, the
      transcriptional regulation of IL-10 expression in proinflammatory T helper (Th) 1
      cells is insufficiently understood. We report a crucial role for the
      transcriptional regulator Blimp-1, induced by IL-12 in a STAT4-dependent manner,
      in controlling IL-10 expression in Th1 cells. Blimp-1 deficiency led to excessive
      inflammation during Toxoplasma gondii infection with increased mortality. IL-10
      production from Th1 cells was strictly dependent on Blimp-1 but was further
      enhanced by the synergistic function of c-Maf, a transcriptional regulator of IL
      10 induced by multiple factors, such as the Notch pathway. We found Blimp-1
      expression, which was also broadly induced by IL-27 in effector T cells, to be
      antagonized by transforming growth factor (TGF) beta. While effectively blocking
      IL-10 production from Th1 cells, TGF-beta shifted IL-10 regulation from a Blimp-1
      dependent to a Blimp-1-independent pathway in IL-27-induced Tr1 (T regulatory 1)
      cells. Our findings further illustrate how IL-10 regulation in Th cells relies on
      several transcriptional programs that integrate various signals from the
      environment to fine-tune expression of this critical immunosuppressive cytokine.

PMID- 25073795
TI  - An enzyme-linked immunosorbent assay for detection of botulinum toxin-antibodies.
AB  - INTRODUCTION: Antibodies against botulinum neurotoxin (BNT-AB) can be detected by
      the mouse protection assay (MPA), the hemidiaphragm assay (HDA), and by enzyme
      linked immunosorbent assays (ELISA). Both MPA and HDA require sacrifice of
      experimental animals, and they are technically delicate and labor intensive. We
      introduce a specially developed ELISA for detection of BNT-A-AB and evaluate it
      against the HDA. METHODS: Thirty serum samples were tested by HDA and by the new
      ELISA. Results were compared, and receiver operating characteristic analyses were
      used to optimize ELISA parameter constellation to obtain either maximal overall
      accuracy, maximal test sensitivity, or maximal test specificity. When the ELISA
      is optimized for sensitivity, a sensitivity of 100% and a specificity of 55% can
      be reached. When it is optimized for specificity, a specificity of 100% and a
      sensitivity of 90% can be obtained. RESULTS: We present an ELISA for BNT-AB
      detection that can be-for the first time-customized for special purposes.
      Adjusted for optimal sensitivity, it reaches the best sensitivity of all BNT-AB
      tests available. CONCLUSIONS: Using the new ELISA together with the HDA as a
      confirmation test allows testing for BNT-AB in large numbers of patients
      receiving BT drugs in an economical, fast, and more animal-friendly way.

PMID- 25073796
TI  - 20-year-old amish woman with abdominal pain, retroperitoneal mass, and
      hyperlipidemia.

PMID- 25073797
TI  - Activity Begins in Childhood (ABC) - inspiring healthy active behaviour in
      preschoolers: study protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: Today's children are more overweight than previous generations and
      physical inactivity is a contributing factor. Modelling and promoting positive
      behaviour in the early years is imperative for the development of lifelong health
      habits. The social and physical environments where children spend their time have
      a powerful influence on behaviour. Since the majority of preschool children spend
      time in care outside of the home, this provides an ideal setting to examine the
      ability of an intervention to enhance movement skills and modify physical
      activity behaviour. This study aims to evaluate the efficacy of the Activity
      Begins in Childhood (ABC) intervention delivered in licensed daycare settings
      alone or in combination with a parent-driven home physical activity-promotion
      component to increase preschoolers' overall physical activity levels and,
      specifically, the time spent in moderate to vigorous physical activity.
      METHODS/DESIGN: This study is a single site, three-arm, cluster-randomized
      controlled trial design with a daycare centre as the unit of measurement
      (clusters). All daycare centres in the National Capital region that serve
      children between the ages of 3 and 5, expressing an interest in receiving the ABC
      intervention will be invited to participate. Those who agree will be randomly
      assigned to one of three groups: i) ABC program delivered at a daycare centre
      only, ii) ABC program delivered at daycare with a home/parental education
      component, or iii) regular daycare curriculum. This study will recruit 18 daycare
      centres, 6 in each of the three groups. The intervention will last approximately
      6 months, with baseline assessment prior to ABC implementation and follow-up
      assessments at 3 and 6 months. DISCUSSION: Physical activity is an acknowledged
      component of a healthy lifestyle and childhood experiences as it has an important
      impact on lifelong behaviour and health. Opportunities for physical activity and
      motor development in early childhood may, over the lifespan, influence the
      maintenance of a healthy body weight and reduce cardiovascular disease risk. If
      successful, the ABC program may be implemented in daycare centres as an effective
      way of increasing healthy activity behaviours of preschoolers. TRIAL
      REGISTRATION: Current Controlled Trials: ISRCTN94022291. Registered in December
      2012, first cluster randomized in April 2013.

PMID- 25073798
TI  - The struggle towards 'the New Normal': a qualitative insight into psychosexual
      adjustment to prostate cancer.
AB  - BACKGROUND: Despite the growing body of literature which highlights the potential
      for significant and enduring side-effects of prostate cancer treatment, there is
      limited research exploring the experience of living with the treatment-induced
      side-effects such as sexual dysfunction, and their repercussions for men and
      their partners. The aim of this qualitative study was to explore factors
      influencing psychosexual adjustment, self-perception, and unmet information and
      support needs of prostate cancer patients and their partners. METHODS: Twenty-one
      men, recruited via a prostate cancer support group newsletter, participated in
      face-to-face semi-structured interviews, which were subjected to thematic
      analysis. RESULTS: The qualitative analysis revealed three inter-connected main
      themes which contributed to men's psychosexual adjustment: i) Psychosexual
      impact, ii) Communication and support, and iii) Integration process. Men reported
      distressing sexual and urinary difficulties, tainted self-perception and altered
      intimate relationships. Receiving adequate information and support, and having
      good communication with their doctors and partners facilitated better adjustment
      to prostate cancer treatment. Coming to terms with the significant impact of
      treatment had involved making lifestyle changes, coping with emotional struggles
      and striving to accept and integrate their post-treatment "new normal" self and
      sexual life. CONCLUSIONS: The importance of adequate communication with health
      professionals and partners, especially regarding treatment effects on sexual
      function and rehabilitation options, was highlighted as a key factor facilitating
      the adjustment process. Prostate cancer patients would benefit from improved
      access to timely and tailored information and decision-making resources, ongoing
      multidisciplinary care, and support groups, as well as appropriate referrals for
      sexual and psychological counselling.

PMID- 25073799
TI  - Paternal germline mosaicism for a GPC3 deletion in X-linked Simpson-Golabi-Behmel
      syndrome.

PMID- 25073800
TI  - Secondary structure estimation and properties analysis of stretched Asian and
      Caucasian hair.
AB  - BACKGROUND: In this previous work, we investigated the secondary structure
      changes of stretched yak hairs by deconvolution, secondary derivation, and curve
      fitting and determined the number of bands and their positions in order to
      resolve the protein spectrum of Raman spectroscopy. OBJECTIVES: The secondary
      structure estimation and properties analysis of stretched Asian and Caucasian
      hair were investigated by Fourier transform infrared spectroscopy, tensile
      curves, and measurement of density. METHODS: The hairs were stretched, dried, and
      baked at ratios 20%, 40%, 60%, 80% and 100%. RESULTS: The analysis of the amide I
      band indicated that the transformation from alpha-helix to beta-pleated structure
      occurred during the stretching process, which could be verified from the tensile
      analysis. The cysteine oxide in S-O vibration area exhibited that stretching led
      to the breakage of the disulfide bonds. When the stretching ratio of Caucasian
      hair was more than a certain ratio, the fiber macromolecular structure was
      destroyed because Caucasian hair had finer diameter and less medulla than Asian
      hair. The beta turn was easier to retract compared with other conformations,
      resulted in the content increase. The density measurements revealed that the
      structure of Caucasian hair was indeed more destroyed than that of Asian hair.
      The cuticles characterization indicated the length of scales was stretched longer
      and the thickness became thinner. Caucasian hair tended to collapse to form small
      fragments at the early stage of stretching. With the increase in stretching
      ratio, the scales of Caucasian hair lifted up, then flaked off and the scale
      interval increased accordingly. Asian hair was more easily peeled off than
      Caucasian hair cuticles with the increase in stretching ratio. CONCLUSIONS: The
      secondary structure of Caucasian hair was destroyed more easily than that of
      Asian hair.

PMID- 25073802
TI  - Forcing aggregation of cyanine dyes with salts: a fine line between dimers and
      higher ordered aggregates.
AB  - It is uncommon to read about cyanine dyes in the literature and not have their
      aggregation discussed. They are of high interest considering their propensity to
      undergo self-organization in aqueous solution, leading to interesting
      photophysical properties resulting from the formation of their dimers and higher
      ordered aggregates. Currently, the study of their aggregation is in high demand
      due to their diverse application range including dye-sensitized solar cells.
      However, their aggregation in high salt solutions is under studied, and the
      effect on aggregation in congruence with high ionic strength is often overlooked.
      In a previous study, our group established the role of specific ion effects and
      in particular the necessity of matching water affinity to induce aggregation of a
      cationic cyanine dye, thiazole orange. In order to advance the understanding of
      this topic, we present in this article the diverse aggregation of cyanine dyes,
      as a single monovalent salt can cause different aggregation responses in a
      variety of these dyes. We established via absorption spectroscopy combined with
      chemometric analyses that the inherent monomer-dimer equilibrium of a dye depends
      on its geometry. More interestingly, experimental data coupled with DFT
      calculations reveal that not only the geometry of a dye but also its charge
      location plays a role in the aggregate morphology formed by the interaction of a
      cationic cyanine dye and an anion. It is thought that contact ion pair formation
      and effective charge screening generated within that ion pair are responsible for
      aggregates with a greater order. 

PMID- 25073801
TI  - Serum CA19-9 as a predictor of malignancy in primary ovarian mucinous tumors: a
      matched case-control study.
AB  - BACKGROUND: This study was designed to investigate the clinical characteristics
      correlated with serum CA19-9 elevation in primary mucinous ovarian tumors and to
      evaluate the role of serum CA19-9 in predicting borderline or malignant tumors.
      MATERIAL/METHODS We retrospectively identified 27 women with pathologically
      confirmed primary ovarian mucinous neoplasms (16 borderline and 11 malignant),
      who had been preoperatively checked for serum CA19-9 and CA125 levels. The
      control group was established by 1:2 matching for age among all women with
      pathologically-confirmed benign mucinous tumors over the same time period. The
      associations of the serum CA19-9 elevation and clinical characteristics,
      including tumor pathology, were evaluated. RESULTS: Serum CA19-9 was more
      frequently elevated in borderline or malignant than benign tumors (57.9% vs.
      16.7%, P=0.001), although the mean value of serum CA19-9 was not significantly
      different among histological subtypes. CA19-9 elevation was correlated with large
      tumor size (largest diameter >=15 cm; p=0.028), serum CA125 elevation (p=0.006),
      and tumor pathology (borderline or malignant tumors; p=0.001). Other clinical
      characteristics, including parity, menopause, bilateral tumor involvement, and
      torsion were not correlated with CA19-9 elevation. Multivariate analysis revealed
      that tumor pathology was the only independent factor for CA19-9 elevation in
      primary ovarian mucinous tumors (odds ratio 3.842, 95% CI 1.277-11.558, p=0.017).
      Interestingly, subgroup analysis in women with normal serum CA 125 level revealed
      that CA19-9 was significantly correlated with borderline and malignant tumors but
      not with benign tumors (odds ratio 6.3, 95% CI 1.438-19.648, p=0.014).
      CONCLUSIONS: Serum CA19-9 can be a useful complementary marker in differentiating
      benign from borderline or malignant mucinous tumors in the ovaries, particularly
      when serum CA125 level is not elevated.

PMID- 25073803
TI  - Not so fast: sleep and media use.

PMID- 25073804
TI  - Space-based visual attention: a marker of immature selective attention in
      toddlers?
AB  - Various studies suggested that attentional difficulties cause toddlers' failure
      in some spatial search tasks. However, attention is not a unitary construct and
      this study investigated two attentional mechanisms: location selection (space
      based attention) and object selection (object-based attention). We investigated
      how toddlers' attention is distributed in the visual field during a manual search
      task for objects moving out of sight, namely the moving boxes task. Results show
      that 2.5-year-olds who failed this task allocated more attention to the location
      of the relevant object than to the object itself. These findings suggest that in
      some manual search tasks the primacy of space-based attention over object-based
      attention could be a marker of immature selective attention in toddlers.

PMID- 25073805
TI  - HMM-ModE: implementation, benchmarking and validation with HMMER3.
AB  - BACKGROUND: HMM-ModE is a computational method that generates family specific
      profile HMMs using negative training sequences. The method optimizes the
      discrimination threshold using 10 fold cross validation and modifies the emission
      probabilities of profiles to reduce common fold based signals shared with other
      sub-families. The protocol depends on the program HMMER for HMM profile building
      and sequence database searching. The recent release of HMMER3 has improved
      database search speed by several orders of magnitude, allowing for the large
      scale deployment of the method in sequence annotation projects. We have rewritten
      our existing scripts both at the level of parsing the HMM profiles and modifying
      emission probabilities to upgrade HMM-ModE using HMMER3 that takes advantage of
      its probabilistic inference with high computational speed. The method is
      benchmarked and tested on GPCR dataset as an accurate and fast method for
      functional annotation. RESULTS: The implementation of this method, which now
      works with HMMER3, is benchmarked with the earlier version of HMMER, to show that
      the effect of local-local alignments is marked only in the case of profiles
      containing a large number of discontinuous match states. The method is tested on
      a gold standard set of families and we have reported a significant reduction in
      the number of false positive hits over the default HMM profiles. When implemented
      on GPCR sequences, the results showed an improvement in the accuracy of
      classification compared with other methods used to classify the familyat
      different levels of their classification hierarchy. CONCLUSIONS: The present
      findings show that the new version of HMM-ModE is a highly specific method used
      to differentiate between fold (superfamily) and function (family) specific
      signals, which helps in the functional annotation of protein sequences. The use
      of modified profile HMMs of GPCR sequences provides a simple yet highly specific
      method for classification of the family, being able to predict the sub-family
      specific sequences with high accuracy even though sequences share common
      physicochemical characteristics between sub-families.

PMID- 25073807
TI  - Relationship-centred care: antidote, guidepost or blind alley? The epistemology
      of 21st century health care.
AB  - Contemporary health care is increasing in complexity and lacks a unifying
      understanding of epistemology, methodology and goals. Lack of conceptual
      consistency in concepts such as 'patient-centred care' (PCC) typifies system-wide
      discordance. We contrast the fragmented descriptions of PCC and related tools to
      its own origins in the writings of Balint and to a subsequent construct,
      relationship-centred care (RCC). We identify the explicit and elaborated
      connection between RCC and a defined epistemological foundation as a
      distinguishing feature of the construct and we demonstrate that this makes
      possible the recognition of alignments between RCC and independently developed
      constructs. Among these, we emphasize Schon's reflective practice, Nonaka's
      theory of organizational knowledge creation and the research methodology of
      realist synthesis. We highlight the relational principles common to these domains
      and to their common epistemologies and illustrate unsatisfying consequences of
      adherence to less adequate epistemological frameworks such as positivism. We
      offer RCC not as an 'antidote' to the dilemmas identified at the outset but as an
      example that illuminates the value and importance of explicit identification of
      the premises and assumptions underlying approaches to improvement of the health
      care system. We stress the potential value of identifying epistemological
      affinities across otherwise disparate fields and disciplines.

PMID- 25073808
TI  - Malignant intraventricular meningioma with craniospinal dissemination and
      concurrent pulmonary metastasis.
AB  - BACKGROUND: Malignant intraventricular meningiomas are quite rare and may spread
      along the craniospinal axis or extraneurally. However, simultaneous cerebrospinal
      dissemination and distal extraneural metastasis has seldom been reported. CASE
      PRESENTATION: A 51-year-old woman presented with recurrent anaplastic meningioma
      in the trigone of right lateral ventricle over a 1.5-year period. Suggested
      radiotherapy was refused after each operation. The patient showed a local relapse
      and dissemination around the previous tumoral cavity and along the spinal canal
      during the last recurrence. Left pulmonary metastasis was also found. She died
      despite multiple lesion resections. CONCLUSIONS: Malignant intraventricular
      meningiomas are an uncommon subset of intracranial meningiomas, and have a great
      potential for intraneural and extraneural metastasis. Systemic investigation for
      metastasis is required after surgery, especially for those without adjuvant
      therapies.

PMID- 25073809
TI  - [What about a new job in the health system: The coordinator of care].

PMID- 25073810
TI  - Potential and limitations of regulatory T-cell therapy in solid organ
      transplantation.
AB  - Over the past few years, the therapeutic potential of Treg has been highlighted
      in the field of autoimmune diseases and after allogeneic transplantation. The
      first hurdle for the therapeutic use of Treg is their insufficient numbers in non
      manipulated individuals, in particular when facing strong immune activation and
      expanding effector cells, such as in response to an allograft. Here we review
      current approaches being explored for Treg expansion in the perspective of
      clinical therapeutic protocols. We describe different Treg subsets that could be
      suitable for clinical application, as well as discuss factors such as the
      required dose of Treg, their antigen-specificity and in vivo stability, that have
      to be considered for optimal Treg-based immunotherapy in transplantation. Since
      Treg may not be sufficient as stand-alone therapy for solid organ transplantation
      in humans, we draw attention to possible hurdles and combination therapy with
      immunomodulatory drugs that could possibly improve the in vivo efficacy of Treg. 

PMID- 25073811
TI  - Antigen-antibody biorecognition events as discriminated by noise analysis of
      force spectroscopy curves.
AB  - Atomic force spectroscopy is able to extract kinetic and thermodynamic parameters
      of biomolecular complexes provided that the registered unbinding force curves
      could be reliably attributed to the rupture of the specific complex interactions.
      To this aim, a commonly used strategy is based on the analysis of the stretching
      features of polymeric linkers which are suitably introduced in the biomolecule
      substrate immobilization procedure. Alternatively, we present a method to select
      force curves corresponding to specific biorecognition events, which relies on a
      careful analysis of the force fluctuations of the biomolecule-functionalized
      cantilever tip during its approach to the partner molecules immobilized on a
      substrate. In the low frequency region, a characteristic 1/f (alpha) noise with
      alpha equal to one (flickering noise) is found to replace white noise in the
      cantilever fluctuation power spectrum when, and only when, a specific
      biorecognition process between the partners occurs. The method, which has been
      validated on a well-characterized antigen-antibody complex, represents a fast,
      yet reliable alternative to the use of linkers which may involve additional
      surface chemistry and reproducibility concerns.

PMID- 25073812
TI  - Rejection despite C5 blockade: a distinct role of IgM?

PMID- 25073813
TI  - [Human anaplasmosis: two case-reports].

PMID- 25073814
TI  - Robust carbon dioxide reduction on molybdenum disulphide edges.
AB  - Electrochemical reduction of carbon dioxide has been recognized as an efficient
      way to convert carbon dioxide to energy-rich products. Noble metals (for example,
      gold and silver) have been demonstrated to reduce carbon dioxide at moderate
      rates and low overpotentials. Nevertheless, the development of inexpensive
      systems with an efficient carbon dioxide reduction capability remains a
      challenge. Here we identify molybdenum disulphide as a promising cost-effective
      substitute for noble metal catalysts. We uncover that molybdenum disulphide shows
      superior carbon dioxide reduction performance compared with the noble metals with
      a high current density and low overpotential (54 mV) in an ionic liquid. Scanning
      transmission electron microscopy analysis and first principle modelling reveal
      that the molybdenum-terminated edges of molybdenum disulphide are mainly
      responsible for its catalytic performance due to their metallic character and a
      high d-electron density. This is further experimentally supported by the carbon
      dioxide reduction performance of vertically aligned molybdenum disulphide. 

PMID- 25073815
TI  - Deaths: preliminary data for 2009.
AB  - Objectives-This report presents preliminary U.S. data on deaths, death rates,
      life expectancy, leading causes of death, and infant mortality for 2009 by
      selected characteristics such as age, sex, race, and Hispanic origin. Methods
      Data in this report are based on death records comprising more than 96 percent of
      the demographic and medical files for all deaths in the United States in 2009.
      The records are weighted to independent control counts for 2009. Comparisons are
      made with 2008 preliminary data. Results-The age-adjusted death rate decreased
      from 758.7 deaths per 100,000 population in 2008 to 741.0 deaths per 100,000
      population in 2009. From 2008 to 2009, age-adjusted death rates decreased
      significantly for 10 of the 15 leading causes of death: Diseases of heart,
      Malignant neoplasms, Chronic lower respiratory diseases, Cerebrovascular
      diseases, Accidents (unintentional injuries), Alzheimer's disease, Diabetes
      mellitus, Influenza and pneumonia, Septicemia, and Assault (homicide). Life
      expectancy increased by 0.2 year, from 78.0 in 2008 to 78.2 in 2009. 

PMID- 25073816
TI  - Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of
      detomidine, medetomidine, and dexmedetomidine in the horse: a population
      analysis.
AB  - The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD)
      relationships of the alpha2-adrenergic receptor agonists detomidine (DET),
      medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in
      vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood
      glucose concentrations were measured over 6 h. Compartmental PK and minimal
      physiologically based PK (mPBPK) models were applied and incorporated into basic
      and extended indirect response models (IRM). Population PK/PD analysis was
      conducted using the Monolix software implementing the stochastic approximation
      expectation maximization algorithm. Marked reductions in HH and HR were found.
      The drug concentrations required to obtain inhibition at half-maximal effect
      (IC50 ) were approximately four times larger for DET than MED and DEX for both HH
      and HR. These effects were not gender dependent. Medetomidine had a greater
      influence on the increase in glucose concentration than DEX. The developed models
      demonstrate the use of mechanistic and mPBPK/PD models for the analysis of
      clinically obtainable in vivo data.

PMID- 25073817
TI  - The genome of the Tiger Milk mushroom, Lignosus rhinocerotis, provides insights
      into the genetic basis of its medicinal properties.
AB  - BACKGROUND: The sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden or Tiger
      milk mushroom (Polyporales, Basidiomycota) is a valuable folk medicine for
      indigenous peoples in Southeast Asia. Despite the increasing interest in this
      ethnobotanical mushroom, very little is known about the molecular and genetic
      basis of its medicinal and nutraceutical properties. RESULTS: The de novo
      assembled 34.3 Mb L. rhinocerotis genome encodes 10,742 putative genes with
      84.30% of them having detectable sequence similarities to others available in
      public databases. Phylogenetic analysis revealed a close evolutionary
      relationship of L. rhinocerotis to Ganoderma lucidum, Dichomitus squalens, and
      Trametes versicolor in the core polyporoid clade. The L. rhinocerotis genome
      encodes a repertoire of enzymes engaged in carbohydrate and glycoconjugate
      metabolism, along with cytochrome P450s, putative bioactive proteins (lectins and
      fungal immunomodulatory proteins) and laccases. Other genes annotated include
      those encoding key enzymes for secondary metabolite biosynthesis, including those
      from polyketide, nonribosomal peptide, and triterpenoid pathways. Among them, the
      L. rhinocerotis genome is particularly enriched with sesquiterpenoid biosynthesis
      genes. CONCLUSIONS: The genome content of L. rhinocerotis provides insights into
      the genetic basis of its reported medicinal properties as well as serving as a
      platform to further characterize putative bioactive proteins and secondary
      metabolite pathway enzymes and as a reference for comparative genomics of
      polyporoid fungi.

PMID- 25073818
TI  - N-functionalized carbon nanotubes as a source and precursor of N
      nitrosodimethylamine: implications for environmental fate, transport, and
      toxicity.
AB  - Hazardous byproducts may be generated during the environmental processing of
      engineered nanomaterials. Here, we explore the ability of carbon nanotubes with
      nitrogen-containing surface groups (N-CNTs) to generate N-nitrosodimethylamine
      (NDMA) during chemical disinfection. Unexpectedly, we observed that commercial N
      CNTs with amine, amide, or N-containing polymer (PABS) surface groups are a
      source of NDMA. As-received powders can leach up to 50 ng of NDMA per mg of N-CNT
      in aqueous suspension; presumably NDMA originates as a residue from N-CNT
      manufacturing. Furthermore, reaction of N-CNTs with free chlorine,
      monochloramine, and ozone generated byproduct NDMA at yields comparable to those
      reported for natural organic matter. Chlorination also altered N-CNT surface
      chemistry, with X-ray photoelectron spectroscopy indicating addition of Cl, loss
      of N, and an increase in surface O. Although these changes can increase N-CNT
      suspension stability, they do not enhance their acute toxicity in E. coli
      bioassays above that observed for as-received powders. Notably, however,
      dechlorination of reacted N-CNTs with sulfite completely suppresses N-CNT
      toxicity. Collectively, our work demonstrates that N-CNTs are both a source and
      precursor of NDMA, a probable human carcinogen, while chemical disinfection can
      produce CNTs exhibiting surface chemistry and environmental behavior distinct
      from that of native (i.e., as-received) materials. 

PMID- 25073819
TI  - [Adrenal pheochromocytoma in a hypertensive patient with a hypertensive crisis].

PMID- 25073820
TI  - [Six-year follow-up of cases of acute alcoholic intoxication among teenagers
      attended at an emergency department].

PMID- 25073821
TI  - [Cribiform-morular variant of papillary thyroid carcinoma as initial presentation
      of the familial adenomatous polyposis].

PMID- 25073822
TI  - [Endocrinologic diseases management during breastfeeding].

PMID- 25073823
TI  - [Follicular thyroid carcinoma with cranial metastasis].

PMID- 25073824
TI  - [Perception of scientific fraud in the Spanish biomedical journals].

PMID- 25073825
TI  - [Influence of weather in the incidence of acute myocardial infarction in Galicia
      (Spain)].
AB  - OBJECTIVE: To assess the interactions between weather and the impact of each
      individual meteorological parameters in the incidence of acute myocardial
      infarctions (AMI) in Galicia. METHODS: Retrospective study analyzing the number
      of AMI diagnosed and transferred to the hospital by the Emergencies Sanitary
      System of Galicia between 2002 and 2009. We included patients with clinical and
      ECG findings of AMI. The correlation between 10-minute meteorological variables
      (temperature, humidity, pressure, accumulated rainfall and wind speed) recorded
      by MeteoGalicia and the incidence of AMI was assessed. RESULTS: A total of 4,717
      AMI were registered (72.8% men, 27.2% women). No seasonal variations were found.
      No significant correlations were detected with regard to average daily
      temperature (P=.683) or wind speed (P=.895). Correlation between atmospheric
      pressure and incidence of AMI was significant (P<.005), as well as with the daily
      relative humidity average (P=.005). CONCLUSIONS: Our study showed a statistical
      significant association with atmospheric pressure and with the daily relative
      humidity average. Since the local conditions of weather are widely variable,
      future studies should establish the relationship between weather patterns
      (including combinations of meteorological parameters), rather than seasonal
      variations, and the incidence of AMI.

PMID- 25073827
TI  - [A 33-year-old man with recurrent polyarthritis].

PMID- 25073826
TI  - [Colorectal Cancer Early Screening Program of Barcelona, Spain: Indicators of the
      first round of a program with participation of community pharmacies].
AB  - BACKGROUND AND OBJECTIVE: The Colorectal Cancer Screening Program of Barcelona
      was implemented in December 2009 and involves pharmacies for the distribution and
      collection of screening tests. The aim of this article is to describe the main
      indicators of the first round of the Program (2010-2011), based on the ones
      suggested by the European Union. MATERIAL AND METHODS: The target population of
      the Colorectal Cancer Screening Program of Barcelona includes men and women aged
      50-69 years who live in the catchment areas of Hospital Clinic and Hospital del
      Mar. Screening consists of biennial immunochemical fecal occult blood testing,
      with colonoscopy as confirmatory procedure. RESULTS: Target population comprised
      197,795 persons. Participation rate was 43.6%, was higher among women and among
      those aged 60 and older. 2.1% of the eligible population stated to have been
      already screened for colorectal cancer. Overall positivity rate was 6.2%, higher
      among men and with a broad variability among health care areas. The detection
      rates of low- and high-risk adenoma, and of invasive cancer were 9.1 0/00, 21.7
      0/00 and 3.1 0/00, respectively. 48.2% of tumors were stage i. CONCLUSIONS: These
      results are considered satisfactory and consistent with those obtained in other
      programs and with European standards. Nevertheless, some areas for improvement
      have been identified. The high participation rate can be attributed, at least in
      part, to the type of test and to the involvement of community pharmacies.

PMID- 25073828
TI  - [Pulmonary arterial hypertension or pulmonary hypertension in patients with human
      immunodeficiency virus infection?].

PMID- 25073829
TI  - [Bullous pemphigoid on surgical scar].

PMID- 25073830
TI  - [Asymptomatic severe aortic stenosis: role of cardiopulmonary exercise testing].

PMID- 25073831
TI  - Racial disparities in adoption of axillary sentinel lymph node biopsy and
      lymphedema risk in women with breast cancer.
AB  - IMPORTANCE: Racial disparities exist in many aspects of breast cancer care.
      Sentinel lymph node biopsy (SLNB) was developed to replace axillary lymph node
      dissection (ALND) for staging early breast cancer to minimize complications.
      Racial disparities in the use of SLNB remain incompletely characterized, and
      their effect on lymphedema risk is not known. OBJECTIVE: To determine racial
      differences in SLNB use among patients with pathologically node-negative breast
      cancer during the period when SLNB became the preferred method for axillary
      staging as well as whether such differences affect lymphedema risk. DESIGN,
      SETTING, AND PARTICIPANTS: A retrospective study was conducted using the
      Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002
      through 2007 to identify cases of incident, nonmetastatic, pathologically node
      negative breast cancer in women aged 66 years or older. MAIN OUTCOMES AND
      MEASURES: Sentinel lymph node biopsy use and 5-year cumulative incidence of
      lymphedema by race. RESULTS: Of 31 274 women identified, 1767 (5.6%) were black,
      27 856 (89.1%) were white, and 1651 (5.3%) were of other or unknown race.
      Sentinel lymph node biopsy was performed in 73.7% of white patients and 62.4% of
      black patients (P < .001). The use of SLNB increased by year for both black and
      white patients (P < .001); however, a fixed disparity of approximately 12
      percentage points in SLNB use persisted through 2007. In adjusted analysis, black
      patients were significantly less likely than white patients to undergo SLNB (odds
      ratio, 0.67; 95% CI, 0.60-0.75; P < .001). Overall, the 5-year cumulative
      lymphedema risk was 8.2% in whites and 12.3% in blacks (hazard ratio [HR], 1.43;
      95% CI, 1.23-1.67; P < .001). When stratified by type of axillary surgery, 5-year
      lymphedema risk was 6.8% in whites undergoing SLNB (HR, 1 [reference]), 8.8% in
      blacks undergoing SLNB (HR, 1.28; 95% CI, 1.02-1.60; P = .03), 12.2% in whites
      undergoing ALND (1.79; 1.63-1.96; P < .001), and 18.0% in blacks undergoing ALND
      (2.76; 2.25-3.39; P < .001). CONCLUSIONS AND RELEVANCE: Although SLNB use
      increased in both black and white patients with pathologically node-negative
      breast cancer from 2002 through 2007, the rates of SLNB remained lower in black
      than white patients during this entire period by approximately 12 percentage
      points. This racial disparity in SLNB use contributed to racial disparities in
      lymphedema risk. Improvements in the dissemination of new techniques are needed
      to avoid disparities in breast cancer care and patient outcomes, particularly in
      disadvantaged groups.

PMID- 25073832
TI  - Selective Na(+) /Ca(2+) exchanger inhibition prevents Ca(2+) overload-induced
      triggered arrhythmias.
AB  - BACKGROUND AND PURPOSE: Augmented Na(+) /Ca(2+) exchanger (NCX) activity may play
      a crucial role in cardiac arrhythmogenesis; however, data regarding the anti
      arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could
      be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the
      experimental model on the degree of Ca(2+) i overload. Hence, we used NCX
      inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of
      NCX inhibition against arrhythmogenic Ca(2+) i rise in conditions when [Ca(2+) ]i
      was augmented via activation of the late sodium current (INaL ) or inhibition of
      the Na(+) /K(+) pump. EXPERIMENTAL APPROACH: Action potentials (APs) were
      recorded from canine papillary muscles and Purkinje fibres by microelectrodes.
      NCX current (INCX ) was determined in ventricular cardiomyocytes utilizing the
      whole-cell patch clamp technique. Ca(2+) i transients (CaTs) were monitored with
      a Ca(2+) -sensitive fluorescent dye, Fluo-4. KEY RESULTS: Enhanced INaL increased
      the Ca(2+) load and AP duration (APD). SEA0400 and ORM10103 suppressed INCX and
      prevented/reversed the anemone toxin II (ATX-II)-induced [Ca(2+) ]i rise without
      influencing APD, CaT or cell shortening, or affecting the ATX-II-induced
      increased APD. ORM10103 significantly decreased the number of strophanthidin
      induced spontaneous diastolic Ca(2+) release events; however, SEA0400 failed to
      restrict the veratridine-induced augmentation in Purkinje-ventricle APD
      dispersion. CONCLUSIONS AND IMPLICATIONS: Selective NCX inhibition - presumably
      by blocking rev INCX (reverse mode NCX current) - is effective against
      arrhythmogenesis caused by [Na(+) ]i -induced [Ca(2+) ]i elevation, without
      influencing the AP waveform. Therefore, selective INCX inhibition, by
      significantly reducing the arrhythmogenic trigger activity caused by the
      perturbed Ca(2+) i handling, should be considered as a promising anti-arrhythmic
      therapeutic strategy.

PMID- 25073835
TI  - The use of high resolution magnetic resonance on 3.0-T system in
      solid/multicystic ameloblastoma surgical planning. Case report.
AB  - OBJECTIVES: The solid/multicystic ameloblastoma is a slowly growing, locally
      invasive epithelial odontogenic tumour. In 80% of cases this lesion occurs in the
      mandible, mainly in the posterior region, and it is characterized by the
      involvement of the inferior alveolar nerve. A panoramic radiograph of a 43-year
      old man with chronic deep pain in the posterior area of the mandible showed a
      multilocular radiolucent lesion with scalloped borders in the left mandibular
      ramus. After the execution of a computed tomography of the jaws, to accurately
      determine the limits of the lesion and the relationship with the the inferior
      alveolar nerve, the magnetic resonance imaging was used. METHODS: The spatial
      relationship between the lesion and the inferior alveolar nerve was defined
      comparing different imaging methods: panoramic radiography, computed tomography
      and magnetic resonance imaging. T1-weighted fast spoiled gradient-recalled echo,
      T1-weighted fast imaging employing steady-state acquisition, T2-weighted
      interactive decomposition of water and fat with echo asymmetry least-squares
      estimation and Diffusion weighted imaging acquisition sequences were used on a
      3.0 T unit. RESULTS: Regarding the inferior alveolar nerve course and its spatial
      relationship with the mandibular lesion, magnetic resonance imaging provided more
      detailed spatial and structural information than other imaging methods.
      CONCLUSION: The described acquisition sequences allowed us to highlight the
      diagnostic efficacy of the magnetic resonance in the morpho-structural
      characterization of a maxillofacial lesion and showed the importance of this
      imaging method as an additional technique to the computerized tomography in the
      maxillofacial surgical planning, resulting in a risk reduction of the inferior
      alveolar nerve surgical injury. KEY WORDS: Ameloblastoma, Mandibular Nerve,
      Magnetic Resonance Imaging, Tomography X-Ray Computed.

PMID- 25073833
TI  - Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on
      cigarette smoking reduction.
AB  - BACKGROUND: This study tests whether the genetic predictor (CHRNA5 nicotine
      receptor gene variants) and an environmental risk factor (partner smoking)
      interact in the prediction of smoking reduction. METHODS: Subjects were from a
      community-based, longitudinal study of women (n=1856) who smoked before
      pregnancy, and a randomized comparative effectiveness smoking cessation trial
      (n=1065). Smoking reduction was defined as the trajectory of self-reported
      smoking quantities over time in the observational study, and as the trajectory of
      alveolar CO levels in the cessation trial. RESULTS: In the pregnancy study,
      rs16969968 genotype and partner smoking status interacted such that the smoking
      reduction was lowest for expectant mothers with high genetic risk and partner
      smoking, and highest for those with high genetic risk but not partner smoking
      (interaction of genotype*partner smoking on smoking quantity trajectory slope
      beta=0.071, 95%CI=0.013, 0.13, p=0.017). In the clinical trial, a similar
      interaction was found (interaction beta=0.20, 95%CI=0.049, 0.36, p=0.010).
      Furthermore, these associations were moderated by pharmacotherapy such that the
      interactive relation of genetic and environmental factors occurred in the placebo
      group, but not in the active pharmacotherapy group (interaction of
      genotype*partner smoking*pharmacotherapy on CO trajectory slope beta=-0.25,
      95%CI=-0.42, -0.091, p=0.0023). CONCLUSIONS: The CHRNA5 genetic risk synergized
      the effect of partner smoking, producing an especially low likelihood of
      successful smoking reduction in two complementary studies. This suggests that the
      genetic vulnerability may be mitigated by altering environmental factors. In
      addition, cessation pharmacotherapy neutralizes the increase in cessation failure
      associated with combined genetic and environmental risks, which has possible
      relevance to treatment algorithms.

PMID- 25073837
TI  - Editorial note: a new section on professional development and greater access to
      journal content.

PMID- 25073834
TI  - Cocaine-, caffeine-, and stress-evoked cocaine reinstatement in high vs. low
      impulsive rats: treatment with allopregnanolone.
AB  - BACKGROUND: Previous research indicates that individual differences in traits
      such as impulsivity, avidity for sweets, and novelty reactivity are predictors of
      several aspects of drug addiction. Specifically, rats that rank high on these
      behavioral measures are more likely than their low drug-seeking counterparts to
      exhibit several characteristics of drug-seeking behavior. In contrast, initial
      work suggests that the low drug-seeking animals are more reactive to negative
      events (e.g., punishment and anxiogenic stimuli). The goal of this study was to
      compare high and low impulsive rats on reinstatement of cocaine-seeking behavior
      elicited by cocaine (COC) and by negative stimuli such as the stress-inducing
      agent yohimbine (YOH) or a high dose of caffeine (CAFF). An additional goal was
      to determine whether treatment with allopregnanolone (ALLO) would reduce
      reinstatement (or relapse) of cocaine-seeking behavior under these priming
      conditions. METHODS: Female rats were selected as high (HiI) or low (LoI)
      impulsive using a delay-discounting task. After selection, they were allowed to
      self-administer cocaine for 12 days. Cocaine was then replaced with saline, and
      rats extinguished lever responding over 16 days. Subsequently, rats were
      pretreated with either vehicle control or ALLO, and cocaine seeking was
      reinstated by injections of COC, CAFF, or YOH. RESULTS: While there were no
      phenotype differences in maintenance and extinction of cocaine self
      administration or reinstatement under control treatment conditions, ALLO
      attenuated COC- and CAFF-primed reinstatement in LoI but not HiI rats.
      CONCLUSIONS: Overall, the present findings suggest that individual differences in
      impulsive behavior may influence efficacy of interventions aimed to reduce drug
      seeking behavior.

PMID- 25073836
TI  - Application site affects the pharmacokinetics of topical testosterone applied to
      the axilla compared with the inner arm.
AB  - PURPOSE: This study compared the pharmacokinetics of a single dose of 1%
      testosterone solution after application to the inner arm or the axilla as
      application sites for transdermal testosterone therapy. METHODS: Healthy, not
      pregnant, premenopausal women, 18 to 45 years of age with a body mass index of 20
      to 28 kg/m(2) were enrolled into a single-center, open-label, randomized, 2-way
      crossover study. Serum total testosterone (TT), free testosterone (fT), and sex
      hormone binding globulin concentrations were measured. Pharmacokinetic parameters
      determined from serum TT and fT included area under the serum concentration
      versus time curve from time zero (pre-dose) until 72 hours post-dose (AUC0-72),
      Cmax, and Tmax. Descriptive statistics were performed on serum concentrations of
      TT and fT for each site. ANOVA was performed on AUC0-72 and Cmax. FINDINGS: A
      single-dose application of 1% testosterone solution to the inner arm and the
      axilla produced clear increases in TT and fT. Slower and lower increases in TT
      and fT were observed after treatment to the inner arm. Based on baseline
      corrected AUC versus time curves, the bioavailability of 1% testosterone solution
      was increased 2-fold for the axilla compared with the inner arm. IMPLICATIONS:
      The absorption of a 1% testosterone solution was significantly greater after
      application to the axilla than to the inner arm. Study number DDS16; Australian
      Therapeutic Goods Administration, CTN 2005/158.

PMID- 25073838
TI  - The Multicultural Family Institute remembers Betty Carter (May 13, 1929-September
      11, 2012).

PMID- 25073839
TI  - Dyadic research in marriage and family therapy: methodological considerations.
AB  - With training that emphasizes relationship systems, marriage and family
      therapists are uniquely attuned to interpersonal dynamics, interdependence, and
      the influence of relationships on individuals' perceptions, beliefs, and
      attitudes. While recent statistical advances have contributed to a proliferation
      of resources designed to introduce researchers to dyadic data analysis,
      guidelines related to the methodological aspects of dyadic research design have
      received less attention. Given the potential advantages of dyadic designs for
      examining couple and family relational and therapeutic processes, the purpose of
      this article is to introduce marriage and family therapy researchers to dyadic
      research methodology. Using examples from our own research, we discuss
      methodological considerations and lessons learned related to sampling,
      measurement, data collection, and ethics. Recommendations for future dyadic
      research are provided.

PMID- 25073840
TI  - Bridging the clinician/researcher gap with systemic research: the case for
      process research, dyadic, and sequential analysis.
AB  - In Marriage and Family Therapy (MFT), as in many clinical disciplines, concern
      surfaces about the clinician/researcher gap. This gap includes a lack of
      accessible, practical research for clinicians. MFT clinical research often
      borrows from the medical tradition of randomized control trials, which typically
      use linear methods, or follow procedures distanced from "real-world" therapy. We
      review traditional research methods and their use in MFT and propose increased
      use of methods that are more systemic in nature and more applicable to MFTs:
      process research, dyadic data analysis, and sequential analysis. We will review
      current research employing these methods, as well as suggestions and directions
      for further research. 

PMID- 25073842
TI  - How couples manage interracial and intercultural differences: implications for
      clinical practice.
AB  - This study focused on how couples managed their interracial and intercultural
      differences. To understand their experiences, a qualitative grounded theory
      analysis was used (n=17). Analysis revealed that couples experienced most issues
      as cultural issues; race only occurred during their interactions with "others."
      They appeared to organize their responses according to four relationship
      structures: Integrated, Singularly Assimilated, Coexisting, and Unresolved.
      Couples in each of these structures managed daily process through four sets of
      relationship strategies: (a) creating a "we," (b) framing differences, (c)
      emotional maintenance, and (d) positioning in relationship to familial and
      societal context. These findings are a step toward a strength-based and research
      informed education and clinical interventions for this population. Video
      Abstract.

PMID- 25073841
TI  - Creating culturally responsive family therapy models and research: introducing
      the use of responsive evaluation as a method.
AB  - Models of marriage and family therapy (MFT) typically reflect Western values and
      norms, and although cultural adaptations are made, many models/frameworks
      continue to be inappropriate or inadequate for use with non-Western cultures.
      Worldwide, therapists are examining ways of using MFT models in a culturally
      sensitive manner, especially when working with clients who are seen as having
      minority status or perceived as "other" by the dominant group. This essay
      suggests the use of responsive evaluation as a theoretically consistent
      methodology for creating and evaluating culturally responsive therapies. This
      approach rigorously evaluates each unique client/therapist context, culture,
      power, needs, and beliefs. We describe responsive evaluation and discuss how each
      component addresses the research needs of examining culturally responsive family
      therapies. A case illustration is offered delineating the process of conducting
      culturally responsive therapy with a Cambodian sample using solution-focused and
      narrative therapy. 

PMID- 25073844
TI  - Social class in family therapy education: experiences of low SES students.
AB  - In this article, we report the results of a national survey of students in
      COAMFTE-accredited family therapy programs who self-identify as coming from lower
      or working-class backgrounds. Results of the study reveal opportunity and
      tension relative to family, friends, and community because of social mobility
      associated with graduate education. Participants describe family therapy
      education as middle-class centered, pointing to lack of attention to social
      class, marginalization, classism, and unacknowledged class barriers as salient
      experiences in their graduate programs. Finally, participants share a number of
      suggestions for program improvement. 

PMID- 25073843
TI  - Exploring social class: voices of inter-class couples.
AB  - Social class is not often discussed or examined in-depth in couple and family
      therapy research and literature even though social class shapes familial
      relationships and is considered an important variable in marital satisfaction. In
      this qualitative study, we explored the perceptions of eight couples who made
      lasting commitments across class lines by asking them about the impact of their
      social class backgrounds on their relationships. Three categories of themes
      emerged including: (a) differences and similarities in values and attitudes
      toward education, work, money, and class awareness/classism, (b) relationship
      issues involving families of origin, friends, and class-based couple conflict,
      and (c) differences in economic resources, social capital and
      privileges/opportunities. Implications for assessment and treatment of couples
      are included. 

PMID- 25073845
TI  - Family therapy retention: an observation of first-session communication.
AB  - This study examined the relationship between communication patterns and retention
      among families (n=18) receiving family therapy. Those that attended 12 sessions
      were labeled completers (n=6), 4-8 sessions were middle dropouts (n=6), and 1-3
      sessions were early dropouts (n=6). Audiotape recordings of the first therapy
      session were transcribed. The content (positive or negative) and total percentage
      of communications by the parent, adolescent, and therapist were coded. Completer
      and middle dropout parents (but not adolescents) showed higher talk time
      proportions than parents in the early dropout group. Completer families had
      higher percentages of therapist-to-parent communications, while early dropout
      families had higher percentages of therapist-to-adolescent communications. There
      were no significant differences between middle dropouts and completers in either
      content or total communications. These findings demonstrate the potential utility
      of examining within-session communication patterns and suggest that within
      session processes may determine therapy retention.

PMID- 25073846
TI  - Child sexual abuse and the superfluous association with negative parenting
      outcomes: the role of symptoms as predictors.
AB  - The purpose of this study was to investigate the relationship between child
      sexual abuse and high-risk maternal parenting indicators and the extent to which
      maternal depression and self-perceived parenting competence influence that
      relationship. Using path analysis, results indicate maternal depression and
      parenting sense of competence mediate the relationship between child sexual abuse
      and outcome variables. Post hoc analyses indicated that child sexual abuse was
      significantly associated with decreased parenting sense of competence,
      controlling for depression. These results highlight that the pathways for
      increased risk in parenting outcomes for child sexual abuse survivors may be
      indirect and associated with beliefs of their own sense of competence and
      depression as opposed to a direct association with sexual abuse itself.
      Implications are discussed. 

PMID- 25073847
TI  - Marriage and family therapy: examining the impact of licensure on an evolving
      profession.
AB  - Regulatory responsibilities for the profession of marriage and family therapy
      have shifted from the American Association of Marriage and Family Therapy (AAMFT)
      to state regulatory boards. The impact of these changes has not been adequately
      addressed. The purpose of this article is to highlight many of these changes and
      explore their implications. The educational, experience, and supervision
      requirements of states regulating the profession of marriage and family therapy
      in 2007 are examined using descriptive data from 47 regulatory entities and then
      compared with the current (2012) regulatory standards from 51 regulatory
      entities. In turn, these are compared with AAMFT prelicensure clinical membership
      requirements. Results indicate a marked difference between AAMFT prelicensure and
      state licensure requirements in both 2007 and 2012, but that state requirements
      continue to evolve. Additionally, the changing roles of the AAMFT and the
      Association of Marital and Family Therapy Regulatory Boards (AMFTRB) within the
      profession are explored. 

PMID- 25073852
TI  - Parasexuality and mosaic aneuploidy in Leishmania: alternative genetics.
AB  - Reproduction as identical or similar organisms in most biological systems depends
      on the extreme accuracy of the mitotic (and meiotic) mechanisms involved in the
      transmission of the genetic material to the two daughter cells. Character
      recombination and genotype diversification are ensured by the alternation between
      haploidy and diploidy, which corresponds to the most predominant model in
      sexually reproducing organisms. In Leishmania, the unique association of high
      levels of automixis and of constitutive 'mosaic aneuploidy' unexpectedly does not
      lead to loss of heterozygosity but constitutes an alternative for genotype
      recombination, hence a source of adaptability. 

PMID- 25073853
TI  - Global regulator Anr represses PlcH phospholipase activity in Pseudomonas
      aeruginosa when oxygen is limiting.
AB  - Haemolytic phospholipase C (PlcH) is a potent virulence and colonization factor
      that is expressed at high levels by Pseudomonas aeruginosa within the mammalian
      host. The phosphorylcholine liberated from phosphatidylcholine and sphingomyelin
      by PlcH is further catabolized into molecules that both support growth and
      further induce plcH expression. We have shown previously that the catabolism of
      PlcH-released choline leads to increased activity of Anr, a global
      transcriptional regulator that promotes biofilm formation and virulence. Here, we
      demonstrated the presence of a negative feedback loop in which Anr repressed plcH
      transcription and we proposed that this regulation allowed for PlcH levels to be
      maintained in a way that promotes productive host-pathogen interactions. Evidence
      for Anr-mediated regulation of PlcH came from data showing that growth at low
      oxygen (1%) repressed PlcH abundance and plcH transcription in the WT, and that
      plcH transcription was enhanced in an Deltaanr mutant. The plcH promoter featured
      an Anr consensus sequence that was conserved across all P. aeruginosa genomes and
      mutation of conserved nucleotides within the Anr consensus sequence increased
      plcH expression under hypoxic conditions. The Anr-regulated transcription factor
      Dnr was not required for this effect. The loss of Anr was not sufficient to
      completely derepress plcH transcription as GbdR, a positive regulator of plcH,
      was required for expression. Overexpression of Anr was sufficient to repress plcH
      transcription even at 21 % oxygen. Anr repressed plcH expression and
      phospholipase C activity in a cell culture model for P. aeruginosa-epithelial
      cell interactions.

PMID- 25073854
TI  - Differences in vaginal microbiome in African American women versus women of
      European ancestry.
AB  - Women of European ancestry are more likely to harbour a Lactobacillus-dominated
      microbiome, whereas African American women are more likely to exhibit a diverse
      microbial profile. African American women are also twice as likely to be
      diagnosed with bacterial vaginosis and are twice as likely to experience preterm
      birth. The objective of this study was to further characterize and contrast the
      vaginal microbial profiles in African American versus European ancestry women.
      Through the Vaginal Human Microbiome Project at Virginia Commonwealth University,
      16S rRNA gene sequence analysis was used to compare the microbiomes of vaginal
      samples from 1268 African American women and 416 women of European ancestry. The
      results confirmed significant differences in the vaginal microbiomes of the two
      groups and identified several taxa relevant to these differences. Major community
      types were dominated by Gardnerella vaginalis and the uncultivated bacterial
      vaginosis-associated bacterium-1 (BVAB1) that were common among African
      Americans. Moreover, the prevalence of multiple bacterial taxa that are
      associated with microbial invasion of the amniotic cavity and preterm birth,
      including Mycoplasma, Gardnerella, Prevotella and Sneathia, differed between the
      two ethnic groups. We investigated the contributions of intrinsic and extrinsic
      factors, including pregnancy, body mass index, diet, smoking and alcohol use,
      number of sexual partners, and household income, to vaginal community
      composition. Ethnicity, pregnancy and alcohol use correlated significantly with
      the relative abundance of bacterial vaginosis-associated species. Trends between
      microbial profiles and smoking and number of sexual partners were observed;
      however, these associations were not statistically significant. These results
      support and extend previous findings that there are significant differences in
      the vaginal microbiome related to ethnicity and demonstrate that these
      differences are pronounced even in healthy women. 

PMID- 25073856
TI  - Prevalence of Kemerovo virus in ixodid ticks from the Russian Federation.
AB  - The prevalence of Kemerovo virus in ixodid ticks collected in 2008-2012 from 11
      regions of the Russian Federation was investigated by real-time reverse
      transcription PCR (RT-PCR). The presence of Kemerovo virus in Ixodes persulcatus,
      Ixodes ricinus, and Dermacentor reticulatus was confirmed. Virus prevalence
      depended on the region and varied from zero to 10.1%. 

PMID- 25073855
TI  - A tool kit for rapid cloning and expression of recombinant antibodies.
AB  - Over the last four decades, molecular cloning has evolved tremendously. Efficient
      products allowing assembly of multiple DNA fragments have become available.
      However, cost-effective tools for engineering antibodies of different
      specificities, isotypes and species are still needed for many research and
      clinical applications in academia. Here, we report a method for one-step assembly
      of antibody heavy- and light-chain DNAs into a single mammalian expression
      vector, starting from DNAs encoding the desired variable and constant regions,
      which allows antibodies of different isotypes and specificity to be rapidly
      generated. As a proof of principle we have cloned, expressed and characterized
      functional recombinant tumor-associated antigen-specific chimeric IgE/kappa and
      IgG1/kappa, as well as recombinant grass pollen allergen Phl p 7 specific fully
      human IgE/lambda and IgG4/lambda antibodies. This method utilizing the antibody
      expression vectors, available at Addgene, has many applications, including the
      potential to support simultaneous processing of antibody panels, to facilitate
      mechanistic studies of antigen-antibody interactions and to conduct early
      evaluations of antibody functions. 

PMID- 25073858
TI  - Oral health disparities of children among Southeast Asian immigrant women in
      arranged transnational marriages in Taiwan.
AB  - This study assessed the oral health disparities and oral health care needs of
      children whose parents are Southeast Asian immigrant women in arranged
      transnational marriages. We used the baseline data of the Lay Health Advisor
      Approach to Promote Oral Health Program (LHA-POHP) to explore the disparities in
      oral health between immigrant and native children, and the factors associated
      with their oral health. A cross-sectional community-based study was conducted to
      collect data from mothers and their preschool children in Southern Taiwan in
      2011. A total of 590 (440 natives, 150 immigrants) children aged 4-6 years and
      their mothers completed the questionnaire and oral examination. Multiple
      regression models were used to analyze the association between children's oral
      health and their related factors. The caries index was 6.05 in immigrant children
      and 3.88 in native children (p < 0.001). The caries prevalence of maxillary
      anterior teeth in the labial surfaces was higher among immigrants, ranging from
      14.7 to 22%. The factor associated with children's caries index was maternal
      tooth brushing frequency (adjusted odds ratio [aOR] = 8.95, 95% confidence
      interval [CI] 1.95-41.05). When the mothers did not direct children to brush
      teeth after eating sweets, their children were more likely to have decayed teeth
      (aOR = 3.54, 95% CI 1.04-12.03). Children's filled teeth were related to their
      dental regular check-ups (aOR = 2.28, 95% CI 1.26-4.10). Disparities in oral
      health among immigrant and native children were observed. The findings suggest
      that culturally adequate oral health promotion intervention programs should be
      implemented for immigrants.

PMID- 25073860
TI  - The factors affecting Nigeria's success toward implementation of global public
      health priorities.
AB  - This paper examines the challenges facing the Nigerian government toward the
      implementation of global public health priories. The Nigerian government
      recognizes the need to implement these priorities by putting in place the
      necessary policy framework, but political instability, poor infrastructural
      development and inadequate funding have remained barriers toward the achievement
      of success in implementing these priorities. The rest of the paper elucidates the
      fact that despite leadership and influence from the World Health Organization and
      other United Nations agencies, and some responses from the Nigerian government,
      tackling these public health problems requires much more fundamental reform to
      primary health services and a reduction in poverty. Although the government has
      shown enough political will to tackle these problems, it is expected that a
      better result will be achieved through injecting more funds into the Nigerian
      health sector, and deploying astute health administrators to manage the sector
      rather than pure health professionals without managerial acumen. 

PMID- 25073857
TI  - Differential effects of insulin sensitization and insulin provision treatment
      strategies on concentrations of circulating adipokines in patients with diabetes
      and coronary artery disease in the BARI 2D trial.
AB  - AIMS: To determine the effects of insulin sensitization (IS) and insulin
      provision (IP) treatment strategies on adipokines associated with cardiovascular
      disease in patients with type 2 diabetes mellitus and coronary artery disease in
      the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (BARI
      2D). METHODS AND RESULTS: Changes in adipokine levels were compared in patients
      with type 2 diabetes mellitus and coronary artery disease randomized to IS (n =
      1037) versus IP (n = 1019) treatment strategies in BARI 2D. Circulating
      concentrations of leptin, adiponectin, monocyte chemoattractant protein-1, tumor
      necrosis factor-alpha, interleukin 6 and C-reactive protein were evaluated at
      baseline and one year. IS and IP treatment strategies exerted significant (p <
      0.0001) differential effects on: leptin (IS: 0.02% decrease, p = 0.01; IP: 13%
      increase, p < 0.0001); adiponectin (IS: 73% increase, p < 0.0001; IP: no change,
      p = 0.52); interleukin 6 (IS: 14% decrease, p < 0.0001; IP: no change, p = 0.68).
      Changes in monocyte chemoattractant protein-1 and tumor necrosis factor-alpha
      were not statistically different between groups. C-reactive protein decreased,
      but the effect was significantly greater in the IS group (-32%, p < 0.0001) than
      in the IP group (-5%, p = 0.0005). CONCLUSION: The IS and IP treatment strategies
      exerted divergent effects on adipokine and inflammatory profile in patients with
      type 2 diabetes mellitus and coronary artery disease. The IS treatment strategy
      induced changes may be more favorable than the IP treatment strategy regarding
      cardiovascular pathophysiology.

PMID- 25073861
TI  - Which environmental factors are associated with performance when controlling for
      capacity?
AB  - OBJECTIVE: To determine which environmental factors are associated with
      performance when controlling for capacity, using the International Classification
      of Functioning, Disability and Health (ICF). METHODS: A psychometric study using
      a sample of 296 persons with musculoskeletal health conditions as a case in
      point. The following steps were carried out: (i) Rasch analyses created 2
      interval measurement scales, capacity and performance, based on 22 Activities and
      Participation ICF categories that had been rated as capacity and performance.
      Capacity and performance scores, ranging from 0 (low level) to 100 (high level)
      were calculated; (ii) group lasso regression was used to identify the
      environmental factors associated with a person's performance when controlling for
      capacity. Gender, age and health condition were forced to remain in the model.
      RESULTS: A capacity scale based on 16 ICF categories (rated as capacity) and a
      performance scale based on 18 categories (rated as performance) were created.
      Thirteen environmental factors ICF categories covering the physical, social,
      attitudinal and political environment were identified as highly associated with
      patient's performance. CONCLUSION: Using an exclusively statistical approach this
      study identified environmental factors associated with a person's performance.

PMID- 25073862
TI  - Expectations from an integrative medicine consultation in breast cancer care: a
      registry protocol-based study.
AB  - PURPOSE: The purpose of this study is to compare the rationale given by oncology
      health care practitioners (HCPs) for referral of their patients with breast
      cancer to a complementary medicine (CM) consultation with patient expectations
      from the CM treatment process. METHODS: We conducted a prospective, registry
      protocol-based, open-label study. We compared the indications given by oncology
      HCPs for their referral of patients to the CM consultation with patient
      expectations from the CM therapeutic process. Patients were asked regarding prior
      CM use for cancer- and non-cancer-related indications. RESULTS: A total of 127
      patients referred to the CM consultation were studied, with half reporting prior
      CM use. The most popular treatment for non-cancer-related indications was
      acupuncture (46.9 %), with only 20.3 % reporting herbal medicine use (P <= 0.04).
      For cancer-related indications, herbal medicine was the most popular modality
      (42.4 %), with 11.6 % reporting acupuncture use. The most frequently cited
      indications for referral were general symptom reduction (19.7 %),
      emotional/spiritual relief (18.1 %), alleviation of weakness and fatigue (17.3
      %), and reduction of gastrointestinal symptoms (10.2 %). For patients, the most
      important outcome was alleviation of weakness and fatigue (70.4 %), followed by
      emotional/spiritual relief (50 %), and the reduction of gastrointestinal symptoms
      (33.3 %). The correlation between HCP indications for referral and patient
      expectations was poor (Cohen's kappa of 0.19, 0.328, and 0.20, respectively).
      CONCLUSIONS: The findings suggest that expectations from a CM treatment process
      differ greatly between oncology HCPs and patients with breast cancer. The use of
      a structured clinical referral process and a better understanding of patient
      concerns are factors which play a central role in the CM referral process.

PMID- 25073863
TI  - Mantle cell lymphoma: a great masquerader.

PMID- 25073864
TI  - Quantifying the average of the time-varying hazard ratio via a class of
      transformations.
AB  - The hazard ratio derived from the Cox model is a commonly used summary statistic
      to quantify a treatment effect with a time-to-event outcome. The proportional
      hazards assumption of the Cox model, however, is frequently violated in practice
      and many alternative models have been proposed in the statistical literature.
      Unfortunately, the regression coefficients obtained from different models are
      often not directly comparable. To overcome this problem, we propose a family of
      weighted hazard ratio measures that are based on the marginal survival curves or
      marginal hazard functions, and can be estimated using readily available output
      from various modeling approaches. The proposed transformation family includes the
      transformations considered by Schemper et al. (Statist Med 28:2473-2489, 2009) as
      special cases. In addition, we propose a novel estimate of the weighted hazard
      ratio based on the maximum departure from the null hypothesis within the
      transformation family, and develop a Kolmogorov[Formula: see text]Smirnov type of
      test statistic based on this estimate. Simulation studies show that when the
      hazard functions of two groups either converge or diverge, this new estimate
      yields a more powerful test than tests based on the individual transformations
      recommended in Schemper et al. (Statist Med 28:2473-2489, 2009), with a similar
      magnitude of power loss when the hazards cross. The proposed estimates and test
      statistics are applied to a colorectal cancer clinical trial. 

PMID- 25073865
TI  - Medical students' perception of dyad practice.
AB  - Training in pairs (dyad practice) has been shown to improve efficiency of
      clinical skills training compared with single practice but little is known about
      students' perception of dyad practice. The aim of this study was to explore the
      reactions and attitudes of medical students who were instructed to work in pairs
      during clinical skills training. A follow-up pilot survey consisting of four open
      ended questions was administered to 24 fourth-year medical students, who
      completed four hours of dyad practice in managing patient encounters. The
      responses were analyzed using thematic analysis. The students felt dyad practice
      improved their self-efficacy through social interaction with peers, provided
      useful insight through observation, and contributed with shared memory of what to
      do, when they forgot essential steps of the physical examination of the patient.
      However, some students were concerned about decreased hands-on practice and many
      students preferred to continue practising alone after completing the initial
      training. Dyad practice is well received by students during initial skills
      training and is associated with several benefits to learning through peer
      observation, feedback and cognitive support. Whether dyad training is suited for
      more advanced learners is a subject for future research. 

PMID- 25073866
TI  - Treatment of melasma with mixed parameters of 1,064-nm Q-switched Nd:YAG laser
      toning and an enhanced effect of ultrasonic application of vitamin C: a split
      face study.
AB  - Melasma is an acquired pigment disorder showing symmetrical hyperpigmentation of
      the face characterized by light to dark brown patches with indistinct borders on
      both cheeks. Melasma is prevalent in middle-aged women with harmless hormone
      imbalances. It is also known as the mask of pregnancy and is prevalent in most
      child-bearing women. It fluctuates month by month, and yet, there is no promising
      treatment. The Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd:YAG)
      laser (1,064-nm wavelength) was introduced in Asia years ago for both skin toning
      and treatment of facial pigment. This low-fluence, 1,064-nm QS-Nd: YAG laser also
      reportedly improved melasma. Adjunctive treatments such as vitamin C
      iontophoresis or chemical peels were recommended in other reports. The technique
      using the 1,064-nm QS-Nd:YAG laser for toning and the enhancement of adjunctive
      treatments need further investigation and long-term follow-up before
      recommendations for the ideal protocol for melasma treatment can be made. The aim
      of this study is to evaluate the improvement of melasma using different
      parameters with the 1,064-nm QS-Nd:YAG laser with ultrasonic application of
      topical vitamin C. Eight patients, ranging in age from 32 to 45 years (mean 37
      years), with long-term melasma were studied. Most of the melasma cases were
      dermal or mixed-type melasma. The patients had no cosmetic treatment (laser,
      intense pulsed light, or chemical peel) 1 year prior to the study. The entire
      face of each patient was treated with the 1,064-nm QS-Nd:YAG laser for four
      sessions at 1-month intervals. The laser treatment was divided into three parts
      with different parameters. First, each patient underwent whole face exposure for
      one pass with an 8-mm spot size at a power of 2.0 J/cm(2). Next, the spot size
      was shifted to 6 mm at a power of 3.5 J/cm(2) for one full-face pass, and then
      ended with a 4-mm spot size at 3.2 J/cm(2) for one full-face pass, with multiple
      passes for the main lesions. The end point was mild erythema and swelling,
      without petechiae. All patients applied ice packs for 5 min before the adjunctive
      treatment. We designed a split-face study with or without ultrasonic application
      of topical vitamin C. Only the right side of the face received ultrasonic melasma
      application of vitamin C for 15 min after ice packing. The left side of the face
      was covered with a moisturizing lotion. Objective evaluation was performed with
      visual analog score. All eight patients completed the 3-month follow-up after the
      four laser treatments. Statistics showed significant improvement with ultrasonic
      application of vitamin C compared to laser monotherapy. The improvement was more
      pronounced during second to fourth sessions. There was no rebound or post
      inflammatory hyperpigmentation detected during the 3-month follow-up period. The
      combination of 1,064-nm QS-Nd:YAG laser treatment with ultrasonic application of
      topical vitamin C exerted more prompt response of melasma. We recommended this
      protocol including mixed parameters of 1,064-nm QS-Nd:YAG laser toning method
      combining with vitamin C ultrasonic application that can yield higher
      satisfaction for the difficult facial pigmentation problems such as melasma.

PMID- 25073867
TI  - Cerebral venous sinus thrombosis: update on diagnosis and management.
AB  - Cerebral venous thrombosis (CVT) is less frequent than ischemic stroke or
      intracerebral haemorrhage. Its incidence is comparable to that of acute bacterial
      meningitis in adults. Because of the increased use of magnetic resonance imaging
      (MR) for investigating patients with acute and subacute headaches and new onset
      seizures, CVT are now being diagnosed with increasing frequency. CVT have a more
      varied clinical presentation than other stroke types as they rarely present as a
      stroke syndrome. Their most frequent presentations are isolated headache,
      intracranial hypertension syndrome, seizures, a focal lobar syndrome and
      encephalopathy. The confirmation of the diagnosis of CVT relies on the
      demonstration of thrombi in the cerebral veins and/or sinuses by MR/MR venography
      or veno CT. The more frequent risk factors for CVT are prothrombotic conditions,
      either genetic or acquired, oral contraceptives, puerperium and pregnancy,
      infection and malignancy. The prognosis of CVT is in general favourable, as only
      around 15% of the patients remain dependent or die. The main intervention in the
      acute is anticoagulation with either low molecular weight or unfractionated
      heparin. In patients in severe condition on admission or who deteriorate despite
      anticoagulation, local thrombolysis or thrombectomy is an option. Decompressive
      surgery is life-saving in patients with large venous infarcts or haemorrhage.
      After the acute phase patients remain anticoagulated for a variable period of
      time, depending on their inherent thrombotic risk. CVT patients may experience
      recurrent seizures. Prophylaxis with antiepileptics is recommended after the
      first seizures, in particular in those with hemispheric lesions. There are
      several ongoing multicentre registries sand trials which will improve evidence
      based management of CVT in the near future.

PMID- 25073868
TI  - An update on stem cell therapies for acute coronary syndrome.
AB  - Well into the second decade since its conception, cell transplantation continues
      to undergo intensive evaluation for the treatment of myocardial infarction. At a
      mechanistic level, its objectives remain to replace lost cardiac cell mass with
      new functioning cardiomyocytes and vascular cells, thereby minimizing infarct
      size and scar formation, and improving clinical outcomes by preventing adverse
      left ventricular remodeling and recurrent ischemic events. Many different cell
      types, including pluripotent stem cells and various adult-derived progenitor
      cells, have been shown to have therapeutic potential in preclinical studies,
      while early phase human trial experience has provided divergent outcomes and
      fundamental lessons, emphasizing that there remain key issues to address and
      challenges to overcome before cell therapy can be applied to wider clinical
      practice. The purpose of this review is to provide a balanced update on recent
      seminal developments in this exciting field and look to the next important steps
      to ensure its forward progression. 

PMID- 25073869
TI  - Investigating the protective effect of lithium against high glucose-induced
      neurotoxicity in PC12 cells: involvements of ROS, JNK and P38 MAPKs, and
      apoptotic mitochondria pathway.
AB  - Hyperglycemia that occurs under the diabetic condition is a major cause of
      diabetic complications such as diabetic neuropathy, one of the most common
      diabetes-related complications. It is well known that hyperglycemia could result
      in generation of reactive oxygen species (ROS). Over production of ROS
      recommended as an important mediator for apoptotic signaling pathway as well as a
      key early event in the development of diabetic neuropathy. Recently, many studies
      have indicated that lithium has robust neuroprotective effect in relation to
      several neurodegenerative diseases. The present study aimed to examine effects of
      lithium on high glucose (HG)-induced neurotoxicity and to determine some of the
      underlying molecular mechanisms involved in this response in PC12 cells as a
      neuronal culture model for diabetic neuropathy. PC12 cells were pretreated with
      different concentrations of lithium for 7 days, exposed to HG for 24 h. Cell
      viability was measured by MTT assay. ROS and lipid peroxidation levels as well as
      superoxide dismutase activity were measured. In order to examine the underlying
      molecular mechanisms, the expressions of Bax, Bcl-2, Caspase-3, total and
      phosphorylated JNK and P38 MAPK were also analyzed by Western blotting. The
      present results indicated that pretreatment with 1 mM lithium has protected PC12
      cells against HG-induced apoptotic cell death. It could reduce ROS generation,
      Bax/Bcl-2 ratio, Caspase-3 activation, and JNK and P38 MAPK phosphorylation. It
      may be concluded that in HG condition, lithium pretreatment could prevent
      mitochondrial apoptosis as well as JNK and P38 MAPK pathway in PC12 cells. 

PMID- 25073871
TI  - Preterm birth and risk of type 1 and type 2 diabetes: systematic review and meta
      analysis.
AB  - Preterm birth is suggested to play an important role in the development of
      diabetes. However, results have been inconsistent. We conducted a systematic
      review and meta-analysis to clarify the relationship between preterm birth and
      type 1 and type 2 diabetes. PubMed, Embase and ISI Web of Science were searched.
      A total of 18 studies (including 2,176,480 participants and 22,073 cases) for
      type 1 diabetes and five studies (including 31,478 participants and 1,898 cases)
      for type 2 diabetes were included in the current meta-analyses. We calculated
      pooled odds ratio (OR) and 95% confidence interval (CI) using fixed-effects model
      to evaluate the relations between preterm birth and type 1 and type 2 diabetes.
      The results suggested that preterm birth was significantly associated with
      increased risk of type 1 diabetes (OR = 1.18, 95% CI = 1.11-1.25), with no
      evidence of between-study heterogeneity (I(2) = 13.2%, P = 0.296). Preterm birth
      was also significantly associated with increased risk of type 2 diabetes (OR =
      1.51, 95% CI = 1.32-1.72), with no evidence of (I(2) = 0.0%, P = 0.557). Subgroup
      analyses suggested that there was significant association in both case-control
      studies (OR = 1.16, 95% CI = 1.06-1.26) and cohort studies (relative risk = 1.20,
      95% CI = 1.11-1.29) for type 1 diabetes, and similar results were found for type
      2 diabetes. The results suggested that preterm birth was a significant and
      independent risk factor for both type 1 and type 2 diabetes.

PMID- 25073870
TI  - Matrix metalloproteinase-1 (MMP-1) expression in rat spinal cord injury model.
AB  - Matrix metalloproteinase-1 (MMP-1), a member of the matrix metalloproteinases
      family, plays an integral role in extracellular matrix degradation and has been
      reportedly involved in the regulation of the brain or spinal cord traumatic
      neurovascular remodeling. Although the critical involvement of MMP-1 in the
      metastasis of tumors has been extensively documented, the role of MMP-1 in the
      pathology of neurological diseases remains largely elusive. In the present study,
      we established an adult rat spinal cord injury (SCI) model and investigated a
      potential role of MMP-1 in the pathological process of SCI. Using Western blot
      analysis, we identified notable expression change of MMP-1 after SCI.
      Immunohistochemistry showed that MMP-1 was distributed widely in rat spinal cord.
      Double immunofluorescence staining revealed that MMP-1 immunoreactivity was
      predominantly increased in neurons and astrocytes following SCI. Moreover, after
      injury, colocalization of MMP-1/active caspase-3 in neurons (NeuN-positive), and
      colocalization of MMP-1/PCNA in astrocytes (GFAP-positive) were clearly observed.
      We also examined the protein expression of PCNA, active caspase-3, Bcl-2, and Bax
      and found that the expression of the proteins was closely correlated with that of
      MMP-1. Taken together, our findings indicate that MMP-1 might play an important
      role in the regulation of neuronal apoptosis and astrocyte proliferation after
      SCI. 

PMID- 25073872
TI  - Preventing amikacin related ototoxicity with N-acetylcysteine in patients
      undergoing peritoneal dialysis.
AB  - Amikacin is a frequently used antibiotic in the treatment of peritoneal dialysis
      (PD)-related peritonitis. Ototoxicity is a well-known complication of amikacin
      for which increased oxidative stress and free oxygen radicals are thought to be
      responsible. In this study, the effect of N-acetyl-cysteine (NAC) on cochlear
      function and oxidant situation in the amikacin related ototoxicity in PD-related
      peritonitis patients are investigated. Forty-six patients who had their first PD
      related peritonitis attacks receiving empirical amikacin treatment were enrolled
      in the study. The patients were randomized into two groups; the first group (n =
      23) as NAC receiving and the second group (n = 23) as a placebo receiving,
      control group. Otoacoustic emissions were measured before, 1 week after and 4
      weeks after the treatment. Oxidative stress measurements were performed
      concurrently in order to evaluate the effectiveness of NAC. The results of
      screening with otoacoustic emission testing after amikacin treatment showed that
      cochlear function is protected especially in higher frequencies in NAC group when
      compared with the control group. Evaluation of the antioxidant status of the two
      groups showed no differences in the basal values, but at the first week there was
      an increase in the NAC group compared with the control group, and this increase
      became significant at the fourth week. NAC is found to be safe and effective in
      amikacin-related ototoxicity in patients with PD-related peritonitis. We suggest
      a close monitoring of the patients receiving amikacin containing treatment
      protocols and if amikacin is administrated supplementing the treatment with NAC.

PMID- 25073873
TI  - Aboriginal and Torres Strait Islander maternal and child health and wellbeing: a
      systematic search of programs and services in Australian primary health care
      settings.
AB  - BACKGROUND: Persistent disparities in pregnancy and birth outcomes between
      Aboriginal and Torres Strait Islander and other Australians evidence a need to
      prioritise responsive practice in Maternal Child Health (MCH). This study
      reviewed the existing knowledge output on Aboriginal and Torres Strait Islander
      MCH programs and services with the objective to advance understanding of the
      current evidence base and inform MCH service development, including the
      identification of new research priorities. METHODS: A systematic search of the
      electronic databases Informit, Proquest, PubMed, Scopus, Wiley, and Cinahl, and 9
      relevant websites was undertaken for the period 1993-2012. The reference lists of
      MCH program reviews were hand-searched for additional relevant studies which met
      the eligibility criteria. The study designs of included publications were
      classified and the characteristics extracted and categorized. Evaluation quality
      was assessed using the Effective Public Health Practice Project (EPHPP) Quality
      Assessment Tool for Quantitative Studies and the Critical Appraisal Skills
      Program (CASP) tool for qualitative studies. RESULTS: Twenty-three search results
      were identified for inclusion, with the majority published in 2003-2012. Fifty
      two percent of publications reported on programs and services operating out of
      Aboriginal Community Controlled Health Organisations, with antenatal and
      postnatal care the main intervention type/s, and health promotion/education and
      advice/support the most common intervention component. Outcomes such as increased
      antenatal attendance and higher infant birth weights were reported in some
      intervention studies, however methodological quality varied considerably with
      quantitative studies typically rated weak. CONCLUSION: The prevalence of
      community controlled and/or community-based programs is significant given the
      health and wellbeing implications of self-determination. While the literature
      highlights the promise of many intervention models and program components used
      there are some significant gaps in the documentation and implementation of
      important MCH interventions. Similarly, while positive health outcomes were
      reported there are issues with key measures used and study quality. This review
      highlights the need to improve the quality of evaluations of MCH programs for
      Aboriginal and Torres Strait Islander women and to address the key evidence gaps
      in responding to their health and wellbeing needs.

PMID- 25073874
TI  - Effect of distractions on operative performance and ability to multitask--a case
      for deliberate practice.
AB  - OBJECTIVES/HYPOTHESIS: To measure the effect of distractions on the operative
      performance and analyze if practice and experience are the factors that can help
      to overcome the distractions. STUDY DESIGN: Prospective observational study.
      METHODS: Ten postgraduate year (PGY) 2-6 residents and two faculty members from
      Johns Hopkins' otolaryngology department were recruited and asked to deepen the
      dissection at the sinodural angle on the Voxel-man mastoidectomy simulator. They
      were asked to perform the task under four conditions: 1) no distractors, 2)
      differentiation and counting of a specific alarm sound among different sounds
      played in the background while performing the surgical task, 3) simultaneous
      performance of simple arithmetic task of moderate difficulty, and 4) simultaneous
      performance of the task with both sets of distractors combined. RESULTS: Time
      taken for the task (P = .02) and error scores (P = .002) increased under the
      third and fourth conditions. The ability to multitask and response to surgical
      and cognitive tasks improved with increasing level of experience of the
      participants. CONCLUSIONS: Distractions lead to impaired dexterity and an
      increase in the incidence of errors. However, experience and deliberate practice
      can help achieve the ability to multitask without compromising the operative
      performance.

PMID- 25073875
TI  - Extensive diversity of Rickettsiales bacteria in two species of ticks from China
      and the evolution of the Rickettsiales.
AB  - BACKGROUND: Bacteria of the order Rickettsiales (Alphaproteobacteria) are
      obligate intracellular parasites that infect species from virtually every major
      eukaryotic lineage. Several rickettsial genera harbor species that are
      significant emerging and re-emerging pathogens of humans. As species of
      Rickettsiales are associated with an extremely diverse host range, a better
      understanding of the historical associations between these bacteria and their
      hosts will provide important information on their evolutionary trajectories and,
      particularly, their potential emergence as pathogens. RESULTS: Nine species of
      Rickettsiales (two in the genus Rickettsia, three in the genus Anaplasma, and
      four in the genus Ehrlichia) were identified in two species of hard ticks
      (Dermacentor nuttalli and Hyalomma asiaticum) from two geographic regions in
      Xinjiang through genetic analyses of 16S rRNA, gltA, and groEL gene sequences.
      Notably, two lineages of Ehrlichia and one lineage of Anaplasma were distinct
      from any known Rickettsiales, suggesting the presence of potentially novel
      species in ticks in Xinjiang. Our phylogenetic analyses revealed some topological
      differences between the phylogenies of the bacteria and their vectors, which led
      us to marginally reject a model of exclusive bacteria-vector co-divergence.
      CONCLUSIONS: Ticks are an important natural reservoir of many diverse species of
      Rickettsiales. In this work, we identified a single tick species that harbors
      multiple species of Rickettsiales, and uncovered extensive genetic diversity of
      these bacteria in two tick species from Xinjiang. Both bacteria-vector co
      divergence and cross-species transmission appear to have played important roles
      in Rickettsiales evolution.

PMID- 25073876
TI  - Metronomic chemotherapy for advanced and refractory cutaneous T-cell lymphoma
      treatment.

PMID- 25073877
TI  - Primary treatment of painful varicocoele through percutaneous retrograde
      embolization with fibred coils.
AB  - The literature on the treatment of painful varicocoele is limited, likely because
      of the short period since it was recognized as a clinical entity and the
      limitations posed by the subjectivity of pain. Our aim was to systematically
      analyse the results of percutaneous embolization as the chosen treatment for this
      condition. We conducted a retrospective study of patients undergoing percutaneous
      embolization as primary treatment for painful varicocoele from January 2007 to
      November 2013. Radiologic and ultrasonographic successes were evaluated according
      to the existence or absence of venous reflux on venography after embolization and
      on Echo Doppler control at 3-6 months. Clinical success was assessed by Visual
      Analog Scale pain questionnaires before surgery and at 3-6 months; in addition,
      at the time of the study, telephone interviews were conducted to update the
      clinical situation and development. A total of 154 patients received operations.
      The median pain before surgery, at 3-6 months and at the time of interview was 7,
      1 and 0 points respectively (p < 0.001). The ultrasonographic success rate at 3-6
      months was 68.6%. With a median follow-up of 39 months, the success and
      relapse/clinical persistence rates were 86.9 and 13.1% respectively. By studying
      the degree of agreement between clinical success and ultrasonographic success, a
      kappa index = 0.443 was obtained. Patients with success recounted greater pre
      operative pain scores than those who relapsed or persisted (7.5 vs. 5.0; p =
      0.004). In patients with painful varicocoele, the ultrasonographic recurrence of
      venous reflux does not imply the recurrence of pain; hence, the proper assessment
      of success in these patients should include a systematic assessment of their pain
      and grade of reflux. Percutaneous retrograde embolization as a primary treatment
      for painful varicocoele is a clinically effective option with a high success rate
      that can be maintained in the long term, especially in patients with high pre
      operative pain.

PMID- 25073878
TI  - Middle-down hybrid chromatography/tandem mass spectrometry workflow for
      characterization of combinatorial post-translational modifications in histones.
AB  - We present an integrated middle-down proteomics platform for sensitive mapping
      and quantification of coexisting PTMs in large polypeptides (5-7 kDa). We
      combined an RP trap column with subsequent weak cation exchange-hydrophilic
      interaction LC interfaced directly to high mass accuracy ESI MS/MS using electron
      transfer dissociation. This enabled automated and efficient separation and
      sequencing of hypermodified histone N-terminal tails for unambiguous localization
      of combinatorial PTMs. We present Histone Coder and IsoScale software to extract,
      filter, and analyze MS/MS data, including quantification of cofragmenting
      isobaric polypeptide species. We characterized histone tails derived from murine
      embryonic stem cells knockout in suppressor of zeste12 (Suz12(-/-) ) and
      quantified 256 combinatorial histone marks in histones H3, H4, and H2A.
      Furthermore, a total of 713 different combinatorial histone marks were identified
      in purified histone H3. We measured a seven-fold reduction of H3K27me2/me3 (where
      me2 and me3 are dimethylation and trimethylation, respectively) in Suz12(-) (/) (
      ) cells and detected significant changes of the relative abundance of 16 other
      single PTMs of histone H3 and other combinatorial marks. We conclude that the
      inactivation of Suz12 is associated with changes in the abundance of not only
      H3K27 methylation but also multiple other PTMs in histone H3 tails.

PMID- 25073879
TI  - Analysis of integrated radiographic data from two long-term, open-label extension
      studies of adalimumab for the treatment of rheumatoid arthritis.
AB  - OBJECTIVE: A longitudinal integration approach evaluated all radiographic scores
      assessed over 10 years, rather than only completer data, from 2 studies of
      adalimumab (ADA) for rheumatoid arthritis (RA). METHODS: The DE019 (methotrexate
      [MTX]-inadequate responders, longstanding RA) and PREMIER (MTX-naive, early RA)
      studies, respectively, had 1- or 2-year double-blind periods followed by 9- or 8
      year open-label extensions (OLEs). Patients received ADA +/- MTX in both OLEs.
      Radiographic progression was assessed using change from baseline in modified
      total Sharp score (DeltamTSS). A mixed-effects model was used post hoc to
      evaluate repeated measurements of different data campaigns and to estimate
      DeltamTSS through up to 10 years of treatment based on original randomization
      groups (placebo [PBO] + MTX or standard dose ADA + MTX). RESULTS: Data from
      patients with baseline and >=1 postbaseline radiograph were included (n = 327 for
      DE019; n = 452 for PREMIER). Integrated and 10-year completer DeltamTSS
      progression curves differed slightly. In DE019, for patients originally assigned
      PBO + MTX, accrued DeltamTSS at year 10 was 6.6 units (integrated model) and 6.2
      units (completers). For patients originally assigned ADA + MTX, accrued DeltamTSS
      was 0.9 units by integrated analysis and 0.7 units in completers. In PREMIER, for
      patients originally assigned PBO + MTX, accrued DeltamTSS at year 10 was 11.2
      units (integrated analysis) and 11.0 units (completers). For patients originally
      assigned ADA + MTX, accrued DeltamTSS was 5.1 units (integrated analysis) and 4.0
      units (completers). A higher radiographic progression rate was observed in
      patients who received delayed versus immediate ADA + MTX treatment. CONCLUSIONS:
      Longitudinal integrated analysis provided robust estimates of radiographic
      progression that only slightly differed from completers-only scores and confirmed
      the effects.

PMID- 25073881
TI  - Evaluation of a nurse mentoring intervention to family caregivers in the
      management of delirium after cardiac surgery (MENTOR_D): a study protocol for a
      randomized controlled pilot trial.
AB  - BACKGROUND: Despite the use of evidence-based preventive measures, delirium
      affects about 40% of patients following cardiac surgery with the potential for
      serious clinical complications and anxiety for caregivers. There is some evidence
      that family involvement as a core component of delirium management may be
      beneficial since familiarity helps patients stay in contact with reality,
      however, this merits further investigation. There is also currently a gap in the
      scientific literature regarding objective indicators that could enhance early
      detection and monitoring of delirium. Therefore, this randomized pilot trial
      examines the acceptability, feasibility, and preliminary efficacy of an
      experimental nursing intervention to help family caregivers manage post-cardiac
      surgery delirium in their relatives. It also explores the validity of a new and
      innovative measure that has potential as an indicator for delirium.
      METHODS/DESIGN: In this two-group randomized pilot study (n = 30), the control
      group will receive usual care and the intervention group will receive the
      experimental intervention aimed at reducing delirium severity. The intervention
      nurse's objective will be to foster the family caregiver's self-efficacy in
      behaving in a supportive manner during delirium episodes. Data will be collected
      from standard delirium assessment scales and a novel measure of delirium, i.e.,
      cerebral oximetry obtained using near infrared spectroscopy, as well as medical
      records and participants' responses to questionnaires. DISCUSSION: New strategies
      for early detection, monitoring, and management of delirium are needed in order
      to improve outcomes for both patients and families. The present article exposes
      feasibility issues based on the first few months of the empirical phase of the
      study that may be useful to the scientific community interested in improving the
      care of patients with delirium. Another potentially important contribution is in
      the exploration of cerebral oximetry, a promising measure as an objective
      indicator for early detection and continuous monitoring of delirium. The proposed
      pilot study will build towards a larger trial with the potential to improve
      knowledge about delirium management and monitoring. TRIAL REGISTRATION: This
      pilot study was registered at Controlled Trials on March 27th 2013 and was
      assigned #ISRCTN95736036.

PMID- 25073882
TI  - Unusual prenatal presentation of Rubinstein-Taybi syndrome: a case report.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare multiple congenital anomalies
      intellectual disability syndrome. The diagnosis is made after birth and based on
      the detection of signs such as growth and developmental delay, minor facial
      anomalies, and broad thumbs and halluces. It is rare to suspect RTS during the
      prenatal period. We report here the approach to a patient with RTS whose
      pregnancy was complicated by multiple congenital anomalies. However, in the
      presence of the broad thumb and facial anomalies, we were able to suggest the
      correct diagnosis. The RTS was confirmed at birth and the molecular analysis of
      the major causative gene revealed a previously unreported heterozygous truncating
      mutation of CREBBP. This report provides new knowledge of the fetal phenotype of
      RTS.

PMID- 25073884
TI  - The long-term use of soap does not affect the pH-maintenance mechanism of human
      skin.
AB  - BACKGROUND: The pH at the surface of healthy human skin is around 5. Cleansing
      the skin with soap increases the pH of the skin, which then returns to a more
      acidic pH within a few hours. However, the effects of skin cleansing with soap
      over a long time on the pH regulatory system is still unclear. OBJECT: We
      compared the pH of the skin between users of a soap-based cleanser and of a mild
      acidic cleanser prior to and following the cleansing. METHOD: This study had two
      groups of subjects, one group who had used a soap-based cleanser for more than 5
      years and the other group who had used a mild-acidic cleanser for more than 5
      years. The pH on the inner forearm of each subject was measured prior to and for
      6 h after cleansing with a soap bar. RESULT: There were no differences between
      the pH of the skin these two groups prior to cleansing, immediately after
      cleansing or in the pH recovery rate for 6 h. CONCLUSION: These results suggest
      that long-term continuous use of a soap-based cleanser does not affect the pH
      maintaining mechanism of human skin.

PMID- 25073883
TI  - Bactericidal activities of GM flax seedcake extract on pathogenic bacteria
      clinical strains.
AB  - BACKGROUND: The antibiotic resistance of pathogenic microorganisms is a worldwide
      problem. Each year several million people across the world acquire infections
      with bacteria that are antibiotic-resistant, which is costly in terms of human
      health. New antibiotics are extremely needed to overcome the current resistance
      problem. RESULTS: Transgenic flax plants overproducing compounds from
      phenylpropanoid pathway accumulate phenolic derivatives of potential
      antioxidative, and thus, antimicrobial activity. Alkali hydrolyzed seedcake
      extract containing coumaric acid, ferulic acid, caffeic acid, and lignan in high
      quantities was used as an assayed against pathogenic bacteria (commonly used
      model organisms and clinical strains). It was shown that the extract components
      had antibacterial activity, which might be useful as a prophylactic against
      bacterial infection. Bacteria topoisomerase II (gyrase) inhibition and genomic
      DNA disintegration are suggested to be the main reason for rendering
      antibacterial action. CONCLUSIONS: The data obtained strongly suggest that the
      seedcake extract preparation is a suitable candidate for antimicrobial action
      with a broad spectrum and partial selectivity. Such preparation can be applied in
      cases where there is a risk of multibacterial infection and excellent answer on
      global increase in multidrug resistance in pathogenic bacteria.

PMID- 25073885
TI  - Continuous rhythm monitoring for ventricular arrhythmias after alcohol septal
      ablation for hypertrophic cardiomyopathy.
AB  - OBJECTIVE: The purpose of the present study was to determine the incidence of
      ventricular arrhythmias before and after alcohol septal ablation (ASA).
      BACKGROUND: In patients with hypertrophic obstructive cardiomyopathy (HOCM),
      gradient reduction by ASA is an alternative for surgical myectomy. However,
      concerns exist about whether the induction of a myocardial scar during ASA may
      create substrate for ventricular arrhythmias. METHODS: The study group consisted
      of 44 patients in whom ASA was performed for symptomatic, drug-refractory
      hypertrophic cardiomyopathy. Continuous rhythm monitoring was obtained by
      implantable loop recorder (n=30) or pacemaker (n=14). Occurrence of ventricular
      and supraventricular arrhythmias before and after ASA was noted, retrospectively.
      RESULTS: The ASA procedure was considered successful (resting gradient <30 mm Hg,
      and provoked gradient <50 mm Hg at 4 months in combination with NYHA Class
      functional status <=2) in 30 (68%) patients. Rhythm monitoring before ASA was
      available in 28 patients. The median duration of rhythm monitoring after ASA was
      3.0 years (IQR 1.3-4.3). Sustained VT/VF within 30 days after ASA occurred in
      three patients (7%), including 2 cases of procedural VF, while no VT/VF was
      observed before ASA (p=0.10). No sustained VT/VF was observed >30 days after ASA.
      No cardiac deaths occurred during follow-up. CONCLUSIONS: In a low-risk cohort of
      patients who underwent ASA, in which continuous rhythm monitoring was performed,
      sustained VT or VF within 30 days occurred in 3 patients (7%) while no VT/VF was
      observed before ASA. During long-term follow-up, no sustained VT or VF was
      observed >30 days after ASA.

PMID- 25073886
TI  - Sudden cardiac death prediction in hypertrophic cardiomyopathy using late
      gadolinium enhancement: trouble in paradise?

PMID- 25073887
TI  - Recurrent ST-segment elevation in infarct-associated leads. Contained left
      ventricular rupture.

PMID- 25073888
TI  - In search for the 'sweet spot' for blood pressure level in diabetes.

PMID- 25073889
TI  - Development of an individualized scoring system to predict mid-term survival
      after carotid endarterectomy.
AB  - BACKGROUND: Carotid endarterectomy (CEA) is a prophylactic surgery focused in
      preventing stroke in the mid-long term. The purpose of this study was to analyze
      mid-term mortality in patients undergoing CEA, identify predictors of 3-year
      mortality and design a score to estimate individual risk of mortality in this
      population. METHODS: A retrospective single-center study including consecutive
      patients undergoing CEA between 1997-2010. Demographic data and comorbidities,
      postoperative results and patient follow-up data were registered and evaluated.
      Kaplan Meier analysis was used to analyze survival. After multivariable COX
      regression analysis, a score based on the calculated Hazards Ratios (HR) was
      designed. The sum of all points performed the individual score for each patient
      for estimating 3-years mortality. Population was stratified into four groups
      according to percentiles of score obtained: Group A (-7 to 4 points), Group B (5
      8 points), Group C (9-10 points), Group D (score greater than 11 points).
      RESULTS: A total of 453 patients with a mean follow-up of 53.4 months were
      included in the study. Overall 3-year survival was 88.4%. On the univariate
      analysis the variables associated with significant increasing in 3-year mortality
      were: female gender (OR 2.32), diabetes mellitus (OR 2.28), COPD (OR 2.98),
      ischemic heart disease (OR 2.29), critical carotid stenosis >90% (OR 2.16) and
      antiplatelet therapy as a protective factor (OR 0,23). Factors associated with
      mortality in multivariate analysis were age (HR 1.14 P=0.001), diabetes mellitus
      (HR 1.62, P=0.031), COPD (HR 1.88 P=0.022), ischemic heart disease (HR 1.59
      P=0.05), critical stenosis >90% (HR 1.70 P=0.015) and antiplatelet therapy as a
      protective factor (HR 0.23 P=0.027). The scoring system includes the following
      items: female gender (+2 points), age (50-69 years +7 points, 70-79 years +12
      points, >80 years +15 points), diabetes (+4 points), COPD (+5 points), ischemic
      heart disease (+4 points), carotid stenosis> 90% (+4 points). Antiplatelet (-7
      points). The score range from -7 to 26 points. The 3-year mortality range was
      5.6% (group A) versus 25.5% (group D). The incidence of stroke at 3-year folllow
      up was not correlated with the score (99%, 100%, 97% and 94.5%, respectively
      groups A-D, P=0.11) CONCLUSIONS: The score developed based on the risk factors of
      mortality allows individualized risk prediction of 3-year mortality in patients
      with carotid stenosis. This represents a useful and practical tool for decision
      making in the indication of the CEA, allowing surgeons to identify high-risk
      patients who would benefit from medical treatment due to their limited life
      expectancy, mainly in asymptomatic patients.

PMID- 25073890
TI  - Comprehensive morphological analysis of individual peripheral neuron dendritic
      arbors in ascidian larvae using the photoconvertible protein Kaede.
AB  - BACKGROUND: Ascidian larval epidermal sensory neurons (ESNs) each extend a single
      cilium into the outer body structure, or tunic, to form a unique external sensory
      network, the ASNET (ascidian dendritic network in tunic). The functions of ESNs
      and the ASNET are unknown, though it has been suggested that they play important
      roles in swimming larvae. In this study, we used transgenic larva expressing the
      photoconvertible protein Kaede pan-neuronally to identify the orientation and
      morphology of single ESN external processes within the ASNET. RESULTS: When
      individual ESN cell bodies were UV-irradiated, the photoconverted Kaede protein
      diffused into the external processes that projected to the edge of the tunic,
      indicating that these processes are cytoplasmically connected to the cell bodies
      of ESNs. We were, therefore, able to comprehensively catalog the morphology and
      orientation of each ESN external process. Most trunk ESNs appeared to extend
      neurites to the palp, but no processes were observed to emanate from palp
      neurons. ESN processes differed systematically in their morphology and
      orientation, suggesting that the ASNET is formed in a regulated, non-random
      fashion. CONCLUSIONS: This study reveals the organization of ESN sensory fields
      in the ascidian larval tunic.

PMID- 25073891
TI  - Caution is needed concerning location of legionella testing, as 1 size (method)
      does not fit all.

PMID- 25073892
TI  - Reply to Uckay et al.

PMID- 25073893
TI  - Reply to Boethel et al.

PMID- 25073895
TI  - Preoperative asymptomatic bacteriuria and subsequent prosthetic joint infection:
      lack of a causal relation.

PMID- 25073894
TI  - HIV-1 DNA decay dynamics in blood during more than a decade of suppressive
      antiretroviral therapy.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) DNA dynamics during long
      term antiretroviral therapy (ART) are not defined. METHODS: Blood mononuclear
      cells obtained during 7-12 years of effective ART were assayed for total HIV-1
      DNA and 2-long terminal repeat (LTR) circles by quantitative polymerase chain
      reaction (qPCR). Slopes of HIV-1 DNA were estimated by participant-specific
      linear regressions. Plasma was assayed for residual viremia (HIV-1 RNA) by qPCR.
      RESULTS: Thirty participants were studied. HIV-1 DNA decreased significantly from
      years 0-1 and 1-4 of ART with median decay slopes of -0.86 (interquartile range, 
      1.05, -0.59) and -0.11 (-0.17, -0.06) log10(copies/10(6) CD4+ T-cells)/year,
      respectively (P < .001). Decay was not significant for years 4-7 (-0.02 [-0.06,
      0.02]; P = .09) or after year 7 of ART (-0.006 [-0.030, 0.015]; P = .17). All
      participants had detectable HIV-1 DNA after 10 years (median 439 copies/10(6)
      CD4+ T-cells; range: 7-2074). Pre-ART HIV-1 DNA levels were positively associated
      with pre-ART HIV-1 RNA levels (Spearman = 0.71, P < .001) and with HIV-1 DNA at
      years 4, 7, and 10 on ART (Spearman >= 0.75, P < .001). No associations were
      found (P >= .25) between HIV-1 DNA slopes or levels and % activated CD8+ T-cells
      (average during years 1-4) or residual viremia (n = 18). 2-LTR circles were
      detected pre-ART in 20/29 and in 8/30 participants at last follow-up.
      CONCLUSIONS: Decay of HIV-1 DNA in blood is rapid in the first year after ART
      initiation (86% decline), slows during years 1-4 (23% decline/year), and
      subsequently plateaus. HIV-1 DNA decay is not associated with the levels of CD8+
      T-cell activation or persistent viremia. The determinants of stable HIV-1 DNA
      persistence require further elucidation. Clinical Trials Registration.
      NCT00001137.

PMID- 25073896
TI  - Tamoxifen monotherapy in the treatment of retroperitoneal fibrosis.
AB  - OBJECTIVE: To evaluate the therapeutic effect of tamoxifen monotherapy in
      patients with retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: From 2007 on,
      31 patients with idiopathic RPF were treated with tamoxifen monotherapy. Follow
      up investigations included magnetic resonance imaging, laboratory measurements,
      registration of side effects and changes or removal of ureteral stents. Data were
      stored in the Else Kroner-Fresenius Registry of Retroperitoneal Fibrosis.
      RESULTS: 25 men and 6 women with a mean age of 56.6 years were treated with
      tamoxifen monotherapy. Mean duration of treatment was 13.3 months, mean follow-up
      26.8 months. A total of 44 renal units were affected by hydronephrosis and
      covered by DJ stents. Radiological regression of fibrosis was detected in 22
      cases (71.0%); removal of ureteral stents was possible in 27/44 renal units
      (61.4%) and 17/29 patients (58.6%), respectively. Most patients showed only mild
      or no side effects of therapy. In 7 cases (22.3%) tamoxifen therapy had to be
      abandoned because of severe side effects, progression of fibrosis or persistent
      intolerance. CONCLUSIONS: Tamoxifen is an alternative in the medical treatment of
      RPF, especially if patients want to avoid glucocorticoids. The potential of
      regression of fibrosis seems to be slightly inferior and the relapse rate is
      higher compared to steroids, but the rate of successful DJ removals is
      comparable.

PMID- 25073897
TI  - Fetal behavioral dynamics in cephalic versus breech presentations.
AB  - Differences in fetal neurodevelopment can have important implications on future
      perceptual and learning capabilities. The aim of this study was to assess
      autonomic nervous system and complexity dynamics in fetal heart rate (FHR)
      tracings from 27 singleton fetuses in cephalic or breech presentations, matched
      for gestational age (37(+3) -40(+4) weeks), weight, gender and outcome. Breeches
      exhibited significantly higher mean FHR and LF/(MF + HF) ratio, as well as lower
      entropy, denoting increased sympatho-vagal balance and decreased complexity,
      consistent with the occurrence of more active fetal behavioral states. These
      findings suggest that there are neurodevelopment differences between fetuses in
      cephalic and breech presentation.

PMID- 25073899
TI  - Molecular characterization of the malaria vector Anopheles barbirostris van der
      Wulp in Sri Lanka.
AB  - BACKGROUND: Anopheles barbirostris is a vector of malaria in Sri Lanka. The taxon
      exists as a species complex in the Southeast Asian region. Previous studies using
      molecular markers suggest that there are more than 4 distinct clades within the
      An. barbirostris complex in Southeast Asia. The present study characterizes Sri
      Lankan An. barbirostris using mtDNA cytochrome oxidase subunit I (COI) and
      ribosomal RNA internal transcribed spacer 2 (ITS2) gene sequences. FINDINGS: DNA
      was extracted from morphologically identified An. barbirostris specimens from Sri
      Lanka, the COI and ITS2 regions amplified and their sequences analysed by
      comparison with other GenBank entries. Maximum likelihood trees suggested that
      Sri Lankan An. barbirostris constitute a different molecular type most closely
      related to clade I. CONCLUSIONS: Considering the uncorrected p distances between
      the clade I and Sri Lankan specimens it is fair to assume that the specimens
      collected from widely separated locations in Sri Lanka with morphology
      characteristic of An. barbirostris s.l. form a new molecular type with close
      resemblance to An. barbirostris s.s from Indonesia and Thailand.

PMID- 25073898
TI  - Breast carcinoma with choriocarcinomatous features: a case report and review of
      the literature.
AB  - BACKGROUND: Breast carcinoma with choriocarcinomatous features (BCCF) is a rare
      variant of breast cancer, characterized by high expression of human chorionic
      gonadotropin (HCG) in cancer cells such as multinucleated syncytiotrophoblast
      like giant cells. The first case of BCCF was reported in 1981 by Saigo and Rosen.
      Only one case of BCCF was reported to show no component of breast ductal
      carcinoma, and only partially cancer cells, such as multinucleated
      syncytiotrophoblast-like giant cells, expressed HCG in all previous BCCF cases.
      Here, we report the first BCCF case without any component of breast ductal
      carcinoma in which HCG was found to express in all cancer cells. CASE
      PRESENTATION: A 32-year-old female patient presented with a small lump in her
      left breast 3 years prior. The mass was clinically suspected to be breast
      infiltrating ductal carcinoma based on breast excisional biopsy and magnetic
      resonance imaging findings. Due to rupture and bleeding of the left kidney, the
      left kidney excisional biopsy was performed. After a retrospective analysis of
      the initial excised breast cancer and breast cancer metastatic to the kidney, the
      cancer cells were positive for HCG by immunohistochemistry, and multinucleated or
      mononucleated giant cells resembled syncytiotrophoblastic and cytotrophoblastic
      cells which could be seen in a background of poor differentiated breast carcinoma
      and extensive necrosis and hemorrhage in the lesion. Thus, a final diagnosis of
      BCCF and BCCF metastatic to the kidney was made. After combination of surgical
      resection (the affected left breast and left kidney wereremoved) and consecutive
      chemotherapy consisting of docetaxel, epirubicin, cisplatin, lobaplatin, and
      capecitabine, the patient achieved favorable therapeutic efficacy (the HCG level
      returned to normal values, the metastatic lesions in the lungs disappeared, and
      the survival was 37 months). Capecitabine was very efficient and highly
      recommended due to its superior efficacy in reducing the HCG level and
      eliminating the metastatic lesions in the lungs. CONCLUSIONS: This is the first
      report of a rare case of BCCF without any component of breast ductal carcinoma,
      featured by high expression of HCG in all cancer cells. Combination of surgery
      and chemotherapy (especially capecitabine) achieved a favorable therapeutic
      efficacy.

PMID- 25073900
TI  - Primary total knee arthroplasty allogenic transfusion trends, length of stay, and
      complications: nationwide inpatient sample 2000-2009.
AB  - Perioperative blood loss leading to blood transfusion continues to be an issue
      for total knee arthroplasty (TKA) patients. The US Nationwide Inpatient Sample
      (NIS) was used to determine annual trends in allogenic blood transfusion rates,
      and effects of transfusion on in-hospital mortality, length of stay (LOS), costs,
      discharge disposition, and complications of primary TKA patients. TKA patients
      between 2000 and 2009 were included (n = 4,544,999) and categorized as: (1) those
      who received a transfusion of allogenic blood, and (2) those who did not.
      Transfusion rates increased from 7.7% to 12.2%. For both transfused and not
      transfused groups, mortality rates and mean LOS declined, while total costs
      increased. Transfused patients were associated with adjusted odds ratios of in
      hospital mortality (AOR 1.16; P = 0.184), 0.71 +/- 0.01 days longer LOS (P <
      0.0001), and incurred ($1777 +/- 36; P < 0.0001) higher total costs per
      admission.

PMID- 25073902
TI  - The provision of aids and adaptations, risk assessments, and incident reporting
      and recording procedures in relation to injury prevention for adults with
      intellectual disabilities: cohort study.
AB  - BACKGROUND: Adults with intellectual disabilities (IDs) experience a higher
      incidence of injury, compared with the general population. The aim of this study
      was to investigate the provision of aids and adaptations, residential service
      providers' individual risk assessments and training in these, and injury incident
      recording and reporting procedures, in relation to injury prevention. METHOD:
      Interviews were conducted with a community-based cohort of adults with IDs (n =
      511) who live in Greater Glasgow, Scotland, UK and their key carer (n = 446).
      They were asked about their aids and adaptations at home, and paid carers (n =
      228) were asked about individual risk assessments, their training, and incident
      recording and reporting procedures. RESULTS: Four hundred and twelve (80.6%) of
      the adults with IDs had at least one aid or adaptation at home to help prevent
      injury. However, a proportion who might benefit, were not in receipt of them, and
      surprisingly few had temperature controlled hot water or a bath thermometer in
      place to help prevent burns/scalds, or kitchen safety equipment to prevent
      burns/scalds from electric kettles or irons. Fifty-four (23.7%) of the paid
      carers were not aware of the adult they supported having had any risk
      assessments, and only 142 (57.9%) had received any training on risk assessments.
      Considerable variation in incident recording and reporting procedures was
      evident. CONCLUSION: More work is needed to better understand, and more fully
      incorporate, best practice injury prevention measures into routine support
      planning for adults with IDs within a positive risk-taking and risk reduction
      framework.

PMID- 25073901
TI  - Can understanding the virulence mechanisms of RNA viruses lead us to a vaccine
      against eastern equine encephalitis virus and other alphaviruses?
AB  - Eastern equine encephalitis virus (EEEV) is a highly neurovirulent mosquito-borne
      alphavirus that causes severe morbidity and mortality upon human infection.
      Recent emergence of EEEV into nonendemic regions in the USA and Panama
      demonstrates the need for the development of an effective EEEV vaccine for
      licensure for human use. The current EEEV vaccine is available to only at-risk
      laboratory workers but is poorly immunogenic and requires multiple boosters. In
      this editorial, we summarize recent developments in understanding alphavirus
      virulence mechanisms that could be utilized to rationally design a live
      attenuated vaccine against EEEV or other alphaviruses. 

PMID- 25073903
TI  - Four-fold Raman enhancement of 2D band in twisted bilayer graphene: evidence for
      a doubly degenerate Dirac band and quantum interference.
AB  - We report the observation of a strong 2D band Raman in twisted bilayer graphene
      (tBLG) with large rotation angles under 638 nm and 532 nm visible laser
      excitations. The 2D band Raman intensity increased four-fold as opposed to the
      two-fold increase observed in single-layer graphene. The same tBLG samples also
      exhibited rotation-dependent G-line resonances and folded phonons under 364 nm UV
      laser excitation. We attribute this 2D band Raman enhancement to the constructive
      interference between two double-resonance Raman pathways, which were enabled by a
      nearly degenerate Dirac band in the tBLG Moire superlattices. 

PMID- 25073904
TI  - Surface energy engineering for tunable wettability through controlled synthesis
      of MoS2.
AB  - MoS2 is an important member of the transition metal dichalcogenides that is
      emerging as a potential 2D atomically thin layered material for low power
      electronic and optoelectronic applications. However, for MoS2 a critical
      fundamental question of significant importance is how the surface energy and
      hence the wettability is altered at the nanoscale in particular, the role of
      crystallinity and orientation. This work reports on the synthesis of large area
      MoS2 thin films on insulating substrates (SiO2/Si and Al2O3) with different
      surface morphology via vapor phase deposition by varying the growth temperatures.
      The samples were examined using transmission electron microscopy and Raman
      spectroscopy. From contact angle measurements, it is possible to correlate the
      wettability with crystallinity at the nanoscale. The specific surface energy for
      few layers MoS2 is estimated to be about 46.5 mJ/m(2). Moreover a layer thickness
      dependent wettability study suggests that the lower the thickness is, the higher
      the contact angle will be. Our results shed light on the MoS2-water interaction
      that is important for the development of devices based on MoS2 coated surfaces
      for microfluidic applications. 

PMID- 25073906
TI  - Interface between path and orbital angular momentum entanglement for high
      dimensional photonic quantum information.
AB  - Photonics has become a mature field of quantum information science, where
      integrated optical circuits offer a way to scale the complexity of the set-up as
      well as the dimensionality of the quantum state. On photonic chips, paths are the
      natural way to encode information. To distribute those high-dimensional quantum
      states over large distances, transverse spatial modes, like orbital angular
      momentum possessing Laguerre Gauss modes, are favourable as flying information
      carriers. Here we demonstrate a quantum interface between these two vibrant
      photonic fields. We create three-dimensional path entanglement between two
      photons in a nonlinear crystal and use a mode sorter as the quantum interface to
      transfer the entanglement to the orbital angular momentum degree of freedom. Thus
      our results show a flexible way to create high-dimensional spatial mode
      entanglement. Moreover, they pave the way to implement broad complex quantum
      networks where high-dimensionally entangled states could be distributed over
      distant photonic chips. 

PMID- 25073905
TI  - In depth annotation of the Anopheles gambiae mosquito midgut transcriptome.
AB  - BACKGROUND: Genome sequencing of Anopheles gambiae was completed more than ten
      years ago and has accelerated research on malaria transmission. However,
      annotation needs to be refined and verified experimentally, as most predicted
      transcripts have been identified by comparative analysis with genomes from other
      species. The mosquito midgut-the first organ to interact with Plasmodium
      parasites-mounts effective antiplasmodial responses that limit parasite survival
      and disease transmission. High-throughput Illumina sequencing of the midgut
      transcriptome was used to identify new genes and transcripts, contributing to the
      refinement of An. gambiae genome annotation. RESULTS: We sequenced ~223 million
      reads from An. gambiae midgut cDNA libraries generated from susceptible (G3) and
      refractory (L35) mosquito strains. Mosquitoes were infected with either
      Plasmodium berghei or Plasmodium falciparum, and midguts were collected after the
      first or second Plasmodium infection. In total, 22,889 unique midgut transcript
      models were generated from both An. gambiae strain sequences combined, and 76%
      are potentially novel. Of these novel transcripts, 49.5% aligned with annotated
      genes and appear to be isoforms or pre-mRNAs of reference transcripts, while
      50.5% mapped to regions between annotated genes and represent novel intergenic
      transcripts (NITs). Predicted models were validated for midgut expression using
      qRT-PCR and microarray analysis, and novel isoforms were confirmed by sequencing
      predicted intron-exon boundaries. Coding potential analysis revealed that 43% of
      total midgut transcripts appear to be long non-coding RNA (lncRNA), and
      functional annotation of NITs showed that 68% had no homology to current
      databases from other species. Reads were also analyzed using de novo assembly and
      predicted transcripts compared with genome mapping-based models. Finally, variant
      analysis of G3 and L35 midgut transcripts detected 160,742 variants with respect
      to the An. gambiae PEST genome, and 74% were new variants. Intergenic transcripts
      had a higher frequency of variation compared with non-intergenic transcripts.
      CONCLUSION: This in-depth Illumina sequencing and assembly of the An. gambiae
      midgut transcriptome doubled the number of known transcripts and tripled the
      number of variants known in this mosquito species. It also revealed existence of
      a large number of lncRNA and opens new possibilities for investigating the
      biological function of many newly discovered transcripts.

PMID- 25073907
TI  - Impact of temperature on mortality in three major Chinese cities.
AB  - OBJECTIVE: To study the relation between temperature and mortality by estimating
      the temperature-related mortality in Beijing, Shanghai, and Guangzhou. METHODS:
      Data of daily mortality, weather and air pollution in the three cities were
      collected. A distributed lag nonlinear model was established and used in
      analyzing the effects of temperature on mortality. Current and future net
      temperature-related mortality was estimated. RESULTS: The association between
      temperature and mortality was J-shaped, with an increased death risk of both hot
      and cold temperature in these cities. The effects of cold temperature on health
      lasted longer than those of hot temperature. The projected temperature-related
      mortality increased with the decreased cold-related mortality. The mortality was
      higher in Guangzhou than in Beijing and Shanghai. CONCLUSION: The impact of
      temperature on health varies in the 3 cities of China, which may have
      implications for climate policy making in China.

PMID- 25073908
TI  - Allergy-related evidences in relation to serum IgE: data from the China state key
      laboratory of respiratory disease, 2008-2013.
AB  - OBJECTIVE: To investigate the serum total IgE (tIgE) and specific IgE (sIgE) to
      common allergens among allergic patients in Guangzhou, China. METHODS: 7 085
      patients were examined for tIgE and sIgE to 15 allergens, based on the protocols
      of reversed enzyme allergosorbent test and the sandwich enzyme-linked
      immunosorbent assay. RESULTS: 3 758 (53.04%) patients tested positive for tIgE,
      and 4 640 (65.49%) for sIgE. Der pteronyssinus, Der farinae, eggs, and cow's milk
      were the most common allergens leading to higher positive rates of sIgE
      responses. Several peaks of sensitization were: Der pteronyssinus, Der farinae,
      and Blomia tropicalis at age 10-12; cow's milk at age below 3; eggs at age 4-6.
      The mean level and positive rate of tIgE tended to increase in subjects
      sensitized to more allergens. Sensitization to Der pteronyssinus (OR, 1.6;
      P<0.05), Der farinae (OR, 1.5; P<0.05), Blomia tropicalis (OR, 1.4; P<0.05),
      Blattella germanica (OR, 1.5; P<0.05), cow's milk (OR, 1.3; P<0.05), and soy
      beans (OR, 2.0; P<0.05) were independently correlated with allergy-related
      conditions in preliminary diagnosis. CONCLUSION: The major allergens in Guangzhou
      include Der pteronyssinus, Der farinae, cow's milk, and eggs. Sensitization to
      these allergens appears to be predictors of allergy-related disorder.

PMID- 25073909
TI  - Induction of apoptosis in hormone-resistant human prostate cancer PC3 cells by
      inactivated Sendai virus.
AB  - OBJECTIVE: Inactivated Sendai virus particle [hemagglutinating virus of Japan
      envelope (HVJ-E)] has a potential oncolytic effect due to its ability to induce
      apoptosis in tumor cells. However, the molecular mechanism of apoptosis induction
      in cancer cells mediated by HVJ-E has not been fully elucidated. This paper aims
      to investigate the underlying mechanism of apoptosis induction by HVJ-E in
      prostate cancer cells (PC3). METHODS: PC3 cells were treated with HVJ-E at
      various MOI, and then interferon-beta (IFN-beta) production, and the cell
      viability and apoptosis were detected by ELISA, MTT-based assay and flow
      cytometry, respectively. Next, the roles of Jak-Stat, MAPK and Akt pathways
      played in HVJ-E-induced apoptosis in PC3 cells were analyzed by immunoblot assay.
      To further evaluate the cytotoxic effect of HVJ-E on PC3 cells, HVJ-E was
      intratumorally injected into prostate cancers on BALB/c-nude mice, and the tumor
      volume was monitored for 36 days. RESULTS: HVJ-E induced IFN-beta production and
      activated Jak-Stat signaling pathway, which resulted in the activation of caspase
      8, caspase-3, and PARP in PC3 prostate cancer cells post HVJ-E treatment.
      Furthermore, we observed for the first time that p38 and Jnk MAPKs in PC3 cells
      contributed to HVJ-E-induced apoptosis. In addition, intratumoral HVJ-E treatment
      displayed a direct inhibitory effect in an in vivo BALB/c nude mouse prostate
      cancer model. CONCLUSION: Our findings have provided novel insights into the
      underlying mechanisms by which HVJ-E induces apoptosis in tumor cells.

PMID- 25073910
TI  - Purification and characterization of a low-temperature hydroxylamine oxidase from
      heterotrophic nitrifier Acinetobacter sp. Y16.
AB  - OBJECTIVE: To purify a low-temperature hydroxylamine oxidase (HAO) from a
      heterotrophic nitrifying bacterium Acinetobacter sp. Y16 and investigate the
      enzyme property. METHODS: A HAO was purified by an anion-exchange and gel
      filtration chromatography from strain Y16. The purity and molecular mass were
      determined by RP-HPLC and SDS-PAGE. The HAO activity was detected by monitoring
      the reduction of potassium ferricyanide using hydroxylamine as substrate and
      ferricyanide as electron acceptor. The partial amino acid sequence was determined
      by mass spectrometry. RESULTS: The low-temperature HAO with a molecular mass of
      61 kDa was purified from strain Y16 by an anion-exchange and gel-filtration
      chromatography. The enzyme exhibited an ability to oxidize hydroxylamine in wide
      temperature range (4-40  degrees C) in vitro using hydroxylamine as substrate and
      ferricyanide as electron acceptor. It was stable in the temperature range of 4 to
      15  degrees C and pH range of 6.0 to 8.5 with less than 30% change in its
      activity. The optimal temperature and pH were 15  degrees C and 7.5,
      respectively. Three peptides were determined by mass spectrometry which were
      shown to be not identical to other reported HAOs. CONCLUSION: This is the first
      study to purify a low-temperature HAO from a heterotrophic nitrifier
      Acinetobacter sp. It differs from other reported HAOs in molecular mass and
      enzyme properties. The findings of the present study have suggested that the
      strain Y16 passes through a hydroxylamine-oxidizing process catalyzed by a low
      temperature HAO for ammonium removal.

PMID- 25073911
TI  - Experimental study on malignant transformation of human bronchial epithelial
      cells induced by glycidyl methacrylate and analysis on its methylation.
AB  - OBJECTIVE: To establish the model of human bronchial epithelial cells (16HBE)
      malignant transformation induced by glycidyl methacrylate (GMA) and define the
      different methylation genes at different stages. METHODS: DNA was extracted at
      different 16HBE malignant phases and changes of genes DNA methylation at
      different stages were detected using Methylation chip of 'NimbleGen HG18 CpG
      Promoter Microarray Methylation'. Methylation-specific PCR (MSP) was used to
      observe the methylation status of some genes, and then compared with the control
      groups. RESULTS: The result showed that GMA induced 16HBE morphorlogical
      transformation at the dose of 8 ug/mL, and cell exposed to GMA had 1374 genes in
      protophase, 825 genes in metaphase, 1149 genes in anaphase, respectively; 30
      genes are all methylation in the 3 stages; 318 genes in protophase but not in
      metaphase and anaphase; 272 genes in metaphase but not in protophase and
      anaphase; 683 genes in anaphase but not in metaphase and protophase; 73 genes in
      protophase and metaphase but not in anaphase; 67 genes in protophase and anaphase
      but not in metaphase; 59 genes in metaphase and anaphase but not in protophase.
      CONCLUSION: The pattern of DNA methylation could change in the process of 16HBE
      induced by GMA.

PMID- 25073912
TI  - Application of positron emission tomography in the detection of myocardial
      metabolism in pig ventricular fibrillation and asphyxiation cardiac arrest models
      after resuscitation.
AB  - OBJECTIVE: To study the application of positron emission tomography (PET) in
      detection of myocardial metabolism in pig ventricular fibrillation and
      asphyxiation cardiac arrest models after resuscitation. METHODS: Thirty-two
      healthy miniature pigs were randomized into a ventricular fibrillation cardiac
      arrest (VFCA) group (n=16) and an asphyxiation cardiac arrest (ACA) group (n=16).
      Cardiac arrest (CA) was induced by programmed electric stimulation or
      endotracheal tube clamping followed by cardiopulmonary resuscitation (CPR) and
      defibrillation. At four hours and 24 h after spontaneous circulation was
      achieved, myocardial metabolism was assessed by PET. 18F-FDG myocardial uptake in
      PET was analyzed and the maximum standardized uptake value (SUVmax) was measured.
      RESULTS: Spontaneous circulation was 100% and 62.5% in VFCA group and ACA group,
      respectively. PET demonstrated that the myocardial metabolism injuries was more
      severe and widespread after ACA than after VFCA. The SUVmax was higher in VFCA
      group than in ACA group (P<0.01). In VFCA group, SUVmax at 24 h after spontaneous
      circulation increased to the level of baseline. CONCLUSION: ACA causes more
      severe cardiac metabolism injuries than VFCA. Myocardial dysfunction is
      associated with less successful resuscitation. Myocardial stunning does occur
      with VFCA but not with ACA.

PMID- 25073913
TI  - Comprehensive level one trauma center could lower in-hospital mortality of severe
      trauma in China.

PMID- 25073914
TI  - Preventing fatal risk through outpatient medical insurance: evidence from urban
      employee basic medical insurance system in Xinjiang Uighur autonomous region,
      China.

PMID- 25073916
TI  - Parsimonious model for blood glucose level monitoring in type 2 diabetes
      patients.
AB  - To establish the parsimonious model for blood glucose monitoring in patients with
      type 2 diabetes receiving oral hypoglycemic agent treatment. One hundred and
      fifty-nine adult Chinese type 2 diabetes patients were randomized to receive
      rapid-acting or sustained-release gliclazide therapy for 12 weeks. Their blood
      glucose levels were measured at 10 time points in a 24 h period before and after
      treatment, and the 24 h mean blood glucose levels were measured. Contribution of
      blood glucose levels to the mean blood glucose level and HbA1c was assessed by
      multiple regression analysis. The correlation coefficients of blood glucose level
      measured at 10 time points to the daily MBG were 0.58-0.74 and 0.59-0.79,
      respectively, before and after treatment (P<0.0001). The multiple stepwise
      regression analysis showed that the blood glucose levels measured at 6 of the 10
      time points could explain 95% and 97% of the changes in MBG before and after
      treatment. The three blood glucose levels, which were measured at fasting, 2 h
      after breakfast and before dinner, of the 10 time points could explain 84% and
      86% of the changes in MBG before and after treatment, but could only explain 36%
      and 26% of the changes in HbA1c before and after treatment, and they had a poorer
      correlation with the HbA1c than with the 24 h MBG. The blood glucose levels
      measured at fasting, 2 h after breakfast and before dinner truly reflected the
      change 24 h blood glucose level, suggesting that they are appropriate for the
      self-monitoring of blood glucose levels in diabetes patients receiving oral anti
      diabetes therapy. 

PMID- 25073915
TI  - Summary of report on cardiovascular diseases in China, 2012.

PMID- 25073917
TI  - Dietary sodium intake and its impact factors in adults of Shandong province.
AB  - Dietary sodium intake and its impact factors in 2 140 adults aged 18-69 years
      were analyzed. The mean daily sodium intake was 5745.0 (5427.6-6062.5) mg per
      day, which was higher in males than in females (P<0.01). After having been
      adjusted for gender, age and urban/city areas, the mean daily sodium intake was
      significantly higher in participants with a lower education level, drinkers and
      smokers than in those with a higher education level, nondrinkers and nonsmokers
      (P<0.01). The dietary sodium intake in adults of Shandong Province is higher than
      the recommended standards. 

PMID- 25073918
TI  - A retrospective cohort mortality study in Jinchang, the largest nickel production
      enterprise in China.

PMID- 25073919
TI  - A review on anticancer potential of bioactive heterocycle quinoline.
AB  - The advent of Camptothecin added a new dimension in the field anticancer drug
      development containing quinoline motif. Quinoline scaffold plays an important
      role in anticancer drug development as their derivatives have shown excellent
      results through different mechanism of action such as growth inhibitors by cell
      cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell
      migration, and modulation of nuclear receptor responsiveness. The anti-cancer
      potential of several of these derivatives have been demonstrated on various
      cancer cell lines. In this review we have compiled and discussed specifically the
      anticancer potential of quinoline derivatives, which could provide a low-height
      flying bird's eye view of the quinoline derived compounds to a medicinal chemist
      for a comprehensive and target oriented information for development of clinically
      viable anticancer drugs. 

PMID- 25073920
TI  - Evaluation of regional limb perfusion with chloramphenicol using the saphenous or
      cephalic vein in standing horses.
AB  - Regional limb perfusion (RLP) significantly decreases morbidity and mortality
      associated with distal limb injuries in horses. There is an urgent need for
      finding additional effective antimicrobial drugs for use in RLP. In this study,
      we tested the pharmacokinetics (PK) of chloramphenicol in RLP. Eight horses
      participated in the study, which was approved by the University Animal Care and
      Use Committee. The cephalic and the saphenous veins were used to perfuse the
      limbs. Synovial samples were collected from the metacarpo/metatarsophalangeal
      (MCP/MTP) joint. The Friedman Test was applied for assessing change in PK
      concentration over time, for all time points. The Wilcoxon Signed Ranks Test was
      used to test the difference between PK concentration in joint & serum as well as
      concentration in joint vs. MIC. The comparison of measurements between
      measurements taken on hind vs. front legs was carried out using the Mann-Whitney
      Test. A P-value of 5% or less was considered statistically significant. After
      RLP, the concentration of chloramphenicol in the synovial fluid of the MCP/MTP
      joint using either the cephalic or the saphenous vein was initially far above the
      minimal inhibitory concentration (MIC) of most susceptible pathogens and remained
      above the MIC for approximately 6 h. The results indicate that performing RLP
      using the cephalic and saphenous veins enables reaching concentrations of
      chloramphenicol in the MCP/MTP joint that are well above the MIC of most
      susceptible pathogens. The chloramphenicol concentrations achieved in the
      synovial fluid of the MCP/MTP joint in the current study were between 1.5 (MTP)
      and 7 (MCP) times the MIC of MRSA in horses. These results are encouraging since
      MRSA infections are becoming far more common, causing considerable morbidity. To
      the best of our knowledge, this is the first study to evaluate the
      pharmacokinetics of chloramphenicol following RLP in the horse and the results
      are positive.

PMID- 25073921
TI  - Vein graft preservation solutions, patency, and outcomes after coronary artery
      bypass graft surgery: follow-up from the PREVENT IV randomized clinical trial.
AB  - IMPORTANCE: In vitro and animal model data suggest that intraoperative
      preservation solutions may influence endothelial function and vein graft failure
      (VGF) after coronary artery bypass graft (CABG) surgery. Clinical studies to
      validate these findings are lacking. OBJECTIVE: To evaluate the effect of vein
      graft preservation solutions on VGF and clinical outcomes in patients undergoing
      CABG surgery. DESIGN, SETTING, AND PARTICIPANTS: Data from the Project of Ex-Vivo
      Vein Graft Engineering via Transfection IV (PREVENT IV) study, a phase 3,
      multicenter, randomized, double-blind, placebo-controlled trial that enrolled
      3014 patients at 107 US sites from August 1, 2002, through October 22, 2003, were
      used. Eligibility criteria for the trial included CABG surgery for coronary
      artery disease with at least 2 planned vein grafts. INTERVENTIONS: Preservation
      of vein grafts in saline, blood, or buffered saline solutions. MAIN OUTCOMES AND
      MEASURES: One-year angiographic VGF and 5-year rates of death, myocardial
      infarction, and subsequent revascularization. RESULTS: Most patients had grafts
      preserved in saline (1339 [44.4%]), followed by blood (971 [32.2%]) and buffered
      saline (507 [16.8%]). Baseline characteristics were similar among groups. One
      year VGF rates were much lower in the buffered saline group than in the saline
      group (patient-level odds ratio [OR], 0.59 [95% CI, 0.45-0.78; P < .001]; graft
      level OR, 0.63 [95% CI, 0.49-0.79; P < .001]) or the blood group (patient-level
      OR, 0.62 [95% CI, 0.46-0.83; P = .001]; graft-level OR, 0.63 [95% CI, 0.48-0.81;
      P < .001]). Use of buffered saline solution also tended to be associated with a
      lower 5-year risk for death, myocardial infarction, or subsequent
      revascularization compared with saline (hazard ratio, 0.81 [95% CI, 0.64-1.02; P
      = .08]) and blood (0.81 [0.63-1.03; P = .09]) solutions. CONCLUSIONS AND
      RELEVANCE: Patients undergoing CABG whose vein grafts were preserved in a
      buffered saline solution had lower VGF rates and trends toward better long-term
      clinical outcomes compared with patients whose grafts were preserved in saline-
      or blood-based solutions. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00042081.

PMID- 25073923
TI  - Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2
      papillary thyroid carcinoma: is it useful?
AB  - INTRODUCTION: The aim of this study was to evaluate the role of prophylactic
      central neck lymph node dissection in high risk patients with T1 or T2 papillary
      thyroid cancer. MATERIALS AND METHODS: Seventy-three patients who had undergone
      total thyroidectomy for papillary thyroid cancer smaller than 4cm, without
      cervical lymphadenopathy and prophylactic central neck lymph node dissection were
      included. Patients were divided in two groups: low risk patients (group A) and
      high risk patients (group B). High risk patients were considered those with at
      least one of the followings: male sex, age >= 45 years, and extracapsular or
      extrathyroid disease. Statistical significant differences in persistent disease,
      recurrence and complications rates between the two groups were studied. RESULTS:
      Persistence of the disease was observed in one case in group A (5.9%) and in
      three cases in group B (5.4%), while thyroid cancer recurrence was registered in
      zero and two (3.6%) cases respectively. One single case (5.9%) of transitory
      recurrent laryngeal nerve damage was reported in group A and none in group B,
      while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A,
      and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was
      observed in one patient in group A, while permanent hypoparathyroidism was
      registered in one case in group B. Logistic regression evidenced that
      multifocality was the only risk factor significantly related to persistence of
      disease and recurrence. CONCLUSIONS: Our results suggests that prophylactic
      central neck lymph node dissection can be safely avoided in patients with T1 or
      T2 papillary thyroid cancer, except in those with multifocal disease. KEY WORDS:
      Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary
      carcinoma, Thyroid.

PMID- 25073922
TI  - Dopamine D1 and corticotrophin-releasing hormone type-2alpha receptors assemble
      into functionally interacting complexes in living cells.
AB  - BACKGROUND AND PURPOSE: Dopamine and corticotrophin-releasing hormone (CRH; also
      known as corticotrophin-releasing factor) are key neurotransmitters in the
      interaction between stress and addiction. Repeated treatment with cocaine
      potentiates glutamatergic transmission in the rat basolateral amygdala/cortex
      pathway through a synergistic action of D1 -like dopamine receptors and CRH type
      2alpha receptors (CRF2 alpha receptors). We hypothesized that this observed
      synergism could be instrumented by heteromers containing the dopamine D1 receptor
      and CRF2 alpha receptor. EXPERIMENTAL APPROACH: D1 /CRF2 alpha receptor
      heteromerization was demonstrated in HEK293T cells using co-immunoprecipitation,
      BRET and FRET assays, and by using the heteromer mobilization strategy. The
      ability of D1 receptors to signal through calcium, when singly expressed or co
      expressed with CRF2 alpha receptors, was evaluated by the calcium mobilization
      assay. KEY RESULTS: D1 /CRF2 alpha receptor heteromers were observed in HEK293T
      cells. When singly expressed, D1 receptors were mostly located at the cell
      surface whereas CRF2 alpha receptors accumulated intracellularly. Interestingly,
      co-expression of both receptors promoted D1 receptor intracellular and CRF2 alpha
      receptor cell surface targeting. The heteromerization of D1 /CRF2 alpha receptors
      maintained the signalling through cAMP of both receptors but switched D1 receptor
      signalling properties, as the heteromeric D1 receptor was able to mobilize
      intracellular calcium upon stimulation with a D1 receptor agonist. CONCLUSIONS
      AND IMPLICATIONS: D1 and CRF2 alpha receptors are capable of heterodimerization
      in living cells. D1 /CRF2 alpha receptor heteromerization might account, at least
      in part, for the complex physiological interactions established between dopamine
      and CRH in normal and pathological conditions such as addiction, representing a
      new potential pharmacological target.

PMID- 25073925
TI  - Flagellar synchronization through direct hydrodynamic interactions.
AB  - Flows generated by ensembles of flagella are crucial to development, motility and
      sensing, but the mechanisms behind this striking coordination remain unclear. We
      present novel experiments in which two micropipette-held somatic cells of Volvox
      carteri, with distinct intrinsic beating frequencies, are studied by high-speed
      imaging as a function of their separation and orientation. Analysis of time
      series shows that the interflagellar coupling, constrained by lack of connections
      between cells to be hydrodynamical, exhibits a spatial dependence consistent with
      theory. At close spacings it produces robust synchrony for thousands of beats,
      while at increasing separations synchrony is degraded by stochastic processes.
      Manipulation of the relative flagellar orientation reveals in-phase and antiphase
      states, consistent with dynamical theories. Flagellar tracking with exquisite
      precision reveals waveform changes that result from hydrodynamic coupling. This
      study proves unequivocally that flagella coupled solely through a fluid can
      achieve robust synchrony despite differences in their intrinsic properties.DOI:
      http://dx.doi.org/10.7554/eLife.02750.001. 

PMID- 25073924
TI  - GSK-3 signaling in developing cortical neurons is essential for radial migration
      and dendritic orientation.
AB  - GSK-3 is an essential mediator of several signaling pathways that regulate
      cortical development. We therefore created conditional mouse mutants lacking both
      GSK-3alpha and GSK-3beta in newly born cortical excitatory neurons. Gsk3-deleted
      neurons expressing upper layer markers exhibited striking migration failure in
      all areas of the cortex. Radial migration in hippocampus was similarly affected.
      In contrast, tangential migration was not grossly impaired after Gsk3 deletion in
      interneuron precursors. Gsk3-deleted neurons extended axons and developed
      dendritic arbors. However, the apical dendrite was frequently branched while
      basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in
      neurons was independent of Wnt/beta-catenin signaling. Importantly,
      phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of
      the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our
      data demonstrate that GSK-3 signaling is essential for radial migration and
      dendritic orientation and suggest that GSK-3 mediates these effects by
      phosphorylating key microtubule regulatory proteins.DOI:
      http://dx.doi.org/10.7554/eLife.02663.001. 

PMID- 25073926
TI  - Integrated action of pheromone signals in promoting courtship behavior in male
      mice.
AB  - The mammalian vomeronasal organ encodes pheromone information about gender,
      reproductive status, genetic background and individual differences. It remains
      unknown how pheromone information interacts to trigger innate behaviors. In this
      study, we identify vomeronasal receptors responsible for detecting female
      pheromones. A sub-group of V1re clade members recognizes gender-identifying cues
      in female urine. Multiple members of the V1rj clade are cognate receptors for
      urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both
      cases, the same cue activates multiple homologous receptors, suggesting
      redundancy in encoding female pheromone cues. Neither gender-specific cues nor
      SEs alone are sufficient to promote courtship behavior in male mice, whereas
      robust courtship behavior can be induced when the two cues are applied together.
      Thus, integrated action of different female cues is required in pheromone
      triggered mating behavior. These results suggest a gating mechanism in the
      vomeronasal circuit in promoting specific innate behavior.DOI:
      http://dx.doi.org/10.7554/eLife.03025.001. 

PMID- 25073927
TI  - Enhancement of encoding and retrieval functions through theta phase-specific
      manipulation of hippocampus.
AB  - Assessing the behavioral relevance of the hippocampal theta rhythm has proven
      difficult, due to a shortage of experiments that selectively manipulate phase
      specific information processing. Using closed-loop stimulation, we triggered
      inhibition of dorsal CA1 at specific phases of the endogenous theta rhythm in
      freely behaving mice. This intervention enhanced performance on a spatial
      navigation task that requires the encoding and retrieval of information related
      to reward location on every trial. In agreement with prior models of hippocampal
      function, the behavioral effects depended on both the phase of theta and the task
      segment at which we stimulated. Stimulation in the encoding segment enhanced
      performance when inhibition was triggered by the peak of theta. Conversely,
      stimulation in the retrieval segment enhanced performance when inhibition was
      triggered by the trough of theta. These results suggest that processes related to
      the encoding and retrieval of task-relevant information are preferentially active
      at distinct phases of theta.DOI: http://dx.doi.org/10.7554/eLife.03061.001. 

PMID- 25073929
TI  - Row with the flow.
AB  - Fluid forces are sufficient to keep flagella beating in synchrony. 

PMID- 25073928
TI  - Intact protein folding in the glutathione-depleted endoplasmic reticulum
      implicates alternative protein thiol reductants.
AB  - Protein folding homeostasis in the endoplasmic reticulum (ER) requires efficient
      protein thiol oxidation, but also relies on a parallel reductive process to edit
      disulfides during the maturation or degradation of secreted proteins. To
      critically examine the widely held assumption that reduced ER glutathione fuels
      disulfide reduction, we expressed a modified form of a cytosolic glutathione
      degrading enzyme, ChaC1, in the ER lumen. ChaC1(CtoS) purged the ER of
      glutathione eliciting the expected kinetic defect in oxidation of an ER-localized
      glutathione-coupled Grx1-roGFP2 optical probe, but had no effect on the disulfide
      editing-dependent maturation of the LDL receptor or the reduction-dependent
      degradation of misfolded alpha-1 antitrypsin. Furthermore, glutathione depletion
      had no measurable effect on induction of the unfolded protein response (UPR); a
      sensitive measure of ER protein folding homeostasis. These findings challenge the
      importance of reduced ER glutathione and suggest the existence of alternative
      electron donor(s) that maintain the reductive capacity of the ER.DOI:
      http://dx.doi.org/10.7554/eLife.03421.001. 

PMID- 25073930
TI  - Phenotypic and genotypic characterization of H2 S-positive and H2 S-negative
      strains of Shewanella baltica isolated from spoiled whiting (Merlangius
      merlangus).
AB  - Four strains were isolated from a spoiled whiting (Merlangius merlangus). All of
      them were able to grow aerobically from 4 to 30 degrees C and also able to
      develop anaerobically in the presence of trimethylamine N-Oxide (TMAO) at 25
      degrees C. Biochemical characterization did not allow identification of the
      strains species but showed that one of the four strains was unable to produce H2
      S. Two strains synthetized an ornithine decarboxylase being potential putrescine
      producers. Results of carbon source use highlighted that the four strains were
      able to use citrate and d-sucrose and one strain was not able to use l-arabinose.
      Genotypic characterization of the strains thanks to 16S rRNA and gyrB partial
      gene sequencing led to their identification as members of Shewanella baltica
      species. These observations suggest that H2 S production may not be the most
      appropriate screening parameter for Shewanella species and further to monitor the
      development of spoilage flora. SIGNIFICANCE AND IMPACT OF THE STUDY: Shewanella
      is a complex genus composed of numerous and heterogeneous species. One of them
      Shewanella baltica has previously been described as one of the most important H2
      S-producing bacterial species in iced stored fish and may act as spoilage
      organism through the reduction of trimethylamine N-Oxide (TMAO). Four strains of
      S. baltica were isolated from spoiled whiting (Merlangius merlangus), and
      description of three H2 S-positive strains and one H2 S-negative strain of S.
      baltica is highlighted in this short paper. Consequently, H2 S production might
      not be the most appropriate screening parameter to assess the development of
      spoilage organisms.

PMID- 25073931
TI  - New horizons: Australian nurses at work in World War I.
AB  - More than 3000 nurses from Australia served with the Australian Army Nursing
      Service or the British nursing services during World War I. These nurses served
      in various theatres of war including Egypt, France, India, Greece, Italy and
      England. They worked in numerous roles including as a surgical team nurse close
      to the front working under fire; nursing on hospital ships carrying the sick and
      wounded; or managing hospital wards overrun with patients whilst dealing with a
      lack of hospital necessities. The skills and roles needed to be a military nurse
      significantly differed to the skills required to nurse in Australia. 

PMID- 25073932
TI  - Rapidly enlarging neck masses of the thyroid with Horner's syndrome: a concise
      clinical review.
AB  - BACKGROUND: Horner's syndrome (HS) presenting with a neck mass is a rare but
      challenging clinical scenario which may be caused by malignant thyroid disease.
      METHODS: A concise review of the literature (PubMED database; 1990-2013) on the
      clinical management of neck masses with HS. An example case is also discussed.
      RESULTS: 1.3% of HS is caused by thyroid pathology. Thyroid pathology is the
      commonest cause of a neck mass associated with HS: the majority are caused by
      benign pathology; with carcinoma and lymphoma accounting for the remainder.
      Anaplastic thyroid carcinoma (ATC), thyroid lymphoma (TL) and thyroid sarcoma
      (TS) typically present with rapidly enlarging anterior neck masses in the elderly
      and are difficult to distinguish clinically. Although fine needle aspirate
      cytology (FNAC) is the diagnostic tool of choice for thyroid masses, core or
      incisional biopsy may be necessary when FNAC is inconclusive. CONCLUSION:
      Differentiation between ATC, TL and TS is imperative as their treatment and
      prognoses differ greatly. Where feasible a combination of surgical debulking,
      radiotherapy and chemotherapy is the treatment of choice in ATC. Advanced cases
      benefit from 2 monthly endoscopic surveillance +/- tracheostomy, stenting or Nd
      YAG laser therapy. Aggressive oncological resection alone is recommended in TS.
      Treatment regimes in thyroid lymphoma (typically chemotherapy +/- radiotherapy)
      differ for histological sub-types. 5-year failure-free survival is 90% in TL
      compared with a mean survival of 6-8 months in ATC and 10 months in TS.

PMID- 25073933
TI  - Thyroid incidentalomas on PET imaging--evaluation of management and clinical
      outcomes.
AB  - OBJECTIVES: 1. To determine the incidence of 'thyroid incidentaloma' in patients
      undergoing PET/CT in Sheffield. 2. To assess the distribution of cancer type,
      stage and short term outcomes of incidentally detected thyroid cancer in this
      cohort. METHODOLOGY: Patients with an unexpected thyroid radio-isotope uptake on
      reports of whole body nuclear imaging performed in Sheffield Teaching Hospitals
      NHS Foundation Trust for 'non-thyroid' indications from April 2008 to March 2011
      were identified. Patients who have undergone PET imaging were then selected. The
      management, clinical and pathology details and short term 'thyroid-related'
      outcomes of patients with thyroid incidentaloma on PET scans were analysed.
      RESULTS: 1730 PET nuclear imaging studies were performed in this period. Thyroid
      incidentalomas were detected in 65 (3.8%)of these scans. Two thyroid cancers were
      detected in this cohort, both demonstrated focal uptake on the PET scan.
      Histology showed papillary thyroid cancer (TNM classification; pT1N1Mx and
      pT1bNxMx). CONCLUSION: The risk of cancer in PET detected thyroid incidentaloma
      in this series (3%) is low compared to published literature (5-50%). Potential
      reasons are discussed. The low rate of thyroid cancer in our incidentaloma cohort
      will influence decision making regarding management of these lesions. Only two
      thyroid cancers were detected in our cohort, limiting the narrative on type,
      stage of PET detected thyroid cancer and outcomes. Further observational research
      is required to study the natural history of these lesions in settings where there
      is a clear protocol for imaging, biopsy and treatment.

PMID- 25073934
TI  - Serum glycated albumin predicts the progression of diabetic retinopathy--a five
      year retrospective longitudinal study.
AB  - AIMS: To assess the predictive value of glycated albumin (GA) and other risk
      factors on a progression of diabetic retinopathy (DR). METHODS: In this
      retrospective longitudinal study, we enrolled the subjects with type 2 diabetes
      who had undergone fundus photography twice with a 5-years gap between January
      2006 and December 2012, and had been measured consecutively for hemoglobin A1c
      (HbA1c) and GA levels every 3 or 6 months. The subjects were divided into two
      groups with or without a progression of DR. The mean HbA1c and mean GA were
      calculated separately by the sum of all measured values divided by the numbers of
      values throughout the study period. RESULTS: Of the 359 subjects, progression
      group showed significantly higher diabetes duration (8.41+/-5.72 vs. 6.46+/-5.77,
      P<0.01), baseline HbA1c (9.13+/-2.71 vs. 8.41+/-2.32, P<0.05), fasting plasma
      glucose (8.71+/-2.78 vs. 7.94+/-2.63, P<0.05), 2h-postprandial glucose (15.12+/
      11.20 vs.13.14+/-4.72, P<0.05), eGFR (114.81+/-39.15 vs. 103.23+/-32.18, P<0.01),
      mean HbA1c (8.32+/-1.69 vs. 7.39+/-1.35, P<0.01) and mean GA (22.66+/-5.92 vs.
      19.83+/-5.18, P<0.01) than non-progression group. The frequencies of subjects
      with DR progression increased obviously with the increment of baseline HbA1c,
      mean HbA1c and mean GA according to quartile stratification of the above three
      glucose parameters. Multivariable binary logistic regression analysis
      investigated that the factors affected the DR progression were the presence of DR
      at baseline (OR=0.391, P=0.005), mean HbA1c (OR=1.389, P=0.021), mean GA
      (OR=1.087, P=0.039) and eGFR (OR=1.008, P=0.045). The optimal cut-off values of
      mean HbA1c and GA to predict DR progression were 7.27% and 21.85%, respectively.
      CONCLUSIONS: The presence of DR at baseline, poor glycemic control, glycated
      albumin, and impaired renal function predicted DR progression in patients with
      type 2 diabetes.

PMID- 25073935
TI  - 5 * 5 cm2 silicon photonic crystal slabs on glass and plastic foil exhibiting
      broadband absorption and high-intensity near-fields.
AB  - Crystalline silicon photonic crystal slabs are widely used in various photonics
      applications. So far, the commercial success of such structures is still limited
      owing to the lack of cost-effective fabrication processes enabling large
      nanopatterned areas (? 1 cm(2)). We present a simple method for producing
      crystalline silicon nanohole arrays of up to 5 * 5 cm(2) size with lattice
      pitches between 600 and 1000 nm on glass and flexible plastic substrates.
      Exclusively up-scalable, fast fabrication processes are applied such as
      nanoimprint-lithography and silicon evaporation. The broadband light trapping
      efficiency of the arrays is among the best values reported for large-area
      experimental crystalline silicon nanostructures. Further, measured photonic
      crystal resonance modes are in good accordance with light scattering simulations
      predicting strong near-field intensity enhancements greater than 500. Hence, the
      large-area silicon nanohole arrays might become a promising platform for
      ultrathin solar cells on lightweight substrates, high-sensitive optical
      biosensors, and nonlinear optics. 

PMID- 25073936
TI  - Skin lesions induced by transcranial direct current stimulation (tDCS).

PMID- 25073937
TI  - Italian deprivation index and dental caries in 12-year-old children: a multilevel
      Bayesian analysis.
AB  - Evidence from the literature has shown that people with a lower socioeconomic
      status enjoy less good health than people with a higher socioeconomic status. The
      Italian deprivation index (DI) was used with the aim to evaluate the association
      between the DMFT index and risk factors for dental caries, including city
      population and DI. The study included 4,305 12-year-old children living in 38
      cities classified by demographic size as small, midsize and large. Zero-inflated
      negative binomial multilevel regression models were used to assess risk factors
      for DMFT and to address excess of zero DMFT and overdispersion through a Bayesian
      approach. The difference in the average level of DMFT among children living in
      cities with different DI quintile was not statistically significant (p = 0.578).
      The DI and ln(population), included as city-level fixed effects in the two-level
      variance components model, were not statistically significant. Consuming sweet
      drinks on average increased the mean DMFT of a susceptible child, while having a
      highly educated mother reduced it. Unobserved heterogeneity among cities was
      detected for the probability to be non-susceptible to caries (city-level variance
      = 0.26 with 95% credibility interval 0.09-0.57), while no territorial effect was
      found for the mean DMFT of the susceptible children. Our results suggest that the
      DI and city population did not play a role in explaining between-city
      variability. Interventions against social deprivation can be influential on the
      perception of oral health in Italian 12-year-old children to the extent that they
      can also affect individual level factors.

PMID- 25073939
TI  - Outcomes of ambulatory rehabilitation programmes following botulinum toxin for
      spasticity in adults with stroke.
AB  - OBJECTIVE: To examine the benefits of high intensity ambulatory rehabilitation
      programmes over usual care following botulinum toxin A (BoNT-A) for post-stroke
      spasticity in Australian adults. DESIGN: Prospective single centre, controlled
      clinical trial. PARTICIPANTS: Fifty-nine adults, median 61 years old and 2.5
      years following stroke. METHODS: PARTICIPANTS were dichotomised into high
      intensity ambulatory rehabilitation programmes (>= 3 * 1-h weekly sessions for
      approximately 10 weeks) or usual care programmes (<= 2 * 1-h weekly sessions)
      following BoNT-A injections for spasticity. A blinded assessor completed outcomes
      at 0 (baseline), 6, 12 and 24 weeks. Primary endpoints: proportion of
      participants achieving >= 50% of their goals (using Goal Attainment Scaling: GAS)
      and GAS T-score change at 12 weeks. SECONDARY OUTCOMES: Modified Ashworth Scale
      (MAS), participant satisfaction, activity/participation measures and caregiver
      burden. RESULTS: Both groups showed significant improvement in goal attainment
      and participant satisfaction up to 24 weeks, with no overall between-group
      significant differences. There was, however, a statistical trend (p = 0.052) for
      participants to achieve more upper limb goals in the high intensity therapy
      group. GAS and satisfaction benefits persisted beyond the duration of spasticity
      reduction as measured by MAS. CONCLUSIONS: While patient-centred outcomes
      following BoNT-A injections for post-stroke spasticity were not influenced by
      intensity of ambulatory rehabilitation programmes, there was a trend for high
      intensity therapy to be associated with greater upper limb goal attainment. This
      suggests that the effects of more intensive therapy may be a modifier of the
      'black box' of rehabilitation; however, further research is required to evaluate
      this effect and determine which elements of therapy programmes optimise post-BoNT
      A outcomes.

PMID- 25073940
TI  - Reoperation rates after fenestration for lumbar spinal canal stenosis: a 20-year
      period survival function method analysis.
AB  - PURPOSE: Fenestration is the gold standard surgery for lumbar spinal canal
      stenosis in Japan. Several previous studies have analyzed the reoperation rates
      in large numbers of patients undergoing several surgical procedures such as
      laminectomy with or without instrumented spinal fusion; however, there have been
      few studies focusing solely on fenestration. The purpose of this study was to
      calculate the reoperation rates after fenestration using the survival function
      method. METHODS: Form 1988-2007, 6,998 surgeries for lumbar spinal canal stenosis
      occurred in Miyagi prefecture, Japan, and these patients were enrolled by the
      spinal surgery registration system of the Department of Orthopaedic Surgery,
      Tohoku University. Among these, 5,835 surgeries involved fenestration as a
      primary surgery and for those who underwent >=2 lumbar surgeries we analyzed the
      reoperation rates using the Kaplan-Meier method. RESULTS: Among the 5,835
      patients undergoing primary fenestration, 215 patients underwent 221 revisions;
      112 included the same spinal levels and 103 were revised only at other levels as
      primary fenestration. The overall reoperation rates were 0.8% at 1 year, 2.9% at
      5 years, 5.2% at 10 years, 7.5% at 15 years and 8.6% at >17.7 years. Reoperation
      rates for those at the same spinal levels were 0.6% at 1 year, 1.7% at 5 years,
      2.7% at 10 years, 3.8% at 15 years, and 4.1% at >17.0 years. CONCLUSIONS:
      Fenestration can be performed at low cost using standard spinal surgery
      equipments. The reoperation rates of this procedure were lower than previously
      reported for several other surgical procedures.

PMID- 25073941
TI  - 'Pseudofacets' or 'supernumerary facets' in congenital atlanto-axial dislocation:
      boon or bane?
AB  - PURPOSE: Certain abnormal contact points, appearing like additional joints
      (pseudofacets) were observed between atlas and axis in a subset of patients with
      congenital atlantoaxial dislocation (CAAD). The origin, function and bearing on
      management of such pseudofacets remain largely undetermined. The object is to
      study 'pseudofacets'or 'accessory joints' in patients with CAAD and to analyze
      the possible genesis, role and bearing of these on surgery and fusion rates.
      MATERIALS AND METHODS: 35 patients with CAAD were analyzed. Reconstructed images
      of CT craniovertebral junction passing through these pseudo and true facets were
      studied. A novel method was devised to measure the faceto-isthmic angle of axis,
      both in patients with CAAD and normal subjects. Operative details and fusion
      rates were studied in patients with pseudofacets and compared with those without
      it. RESULTS: Eight out of 35 patients (6 Irreducible CAAD and 2 with RCAAD) had
      pseudofacets. These are seen posterior to the true facets and resemble partially
      formed joints. The C2 facet was acutely bent over its isthmus in these patients.
      The direction of these pseudofacets appeared to counter the abnormal mobility at
      C1-2 true facets. Intraoperatively, they posed a visual hindrance to reach up to
      true facets for placement of spacers and lateral mass screws, requiring extensive
      drilling. At the same time, they did help in distraction and increased the
      surface for fusion between C1 and C2 in cases where sublaminar wiring alone was
      used. Fusion rates were 100 % in patients with pseudofacets. CONCLUSIONS:
      Pseudofacets may be a result of genetic aberration and nature's mechanism to
      restrict abnormal C1-2 mobility in CAAD by imparting some stability. Their
      presence hinders the visualization making it difficult to reach upto the true
      facets, thus a bane. They may require extensive drilling when direct posterior
      approach is used, thereby disrupting the natural restrictive mechanism. However,
      the flattened surfaces provide an increased area for postoperative bony fusion
      between C1 and 2, making their presence a 'boon'.

PMID- 25073942
TI  - A prospective randomised controlled trial to assess the efficacy of dynamic
      stabilisation of the lumbar spine with the Wallis ligament.
AB  - PURPOSE: This prospective randomised control study is to demonstrate whether or
      not there is a clinical benefit from inserting a Wallis implant on the functional
      recovery of patients who have undergone lumbar decompression surgery. METHOD:
      Sixty consecutive patients with an average age of 58 years (34-81) who were
      selected for primary lumbosacral decompression were randomly assigned into two
      groups with equal number of patients, decompression alone or decompression with
      Wallis implant. The patients had an average follow-up of 40 months. Patients were
      assessed by visual analogue scale (VAS) (Boonstra et al., Int J Rehabil Res
      31:165-169, 2008; Price et al., Pain 17:45-56, 1983) pain score for back and leg
      pain, and the Oswestry Disability Index questionnaire (ODI) (Smeets et al.,
      Arthritis Care Res (Hoboken) 63:S158-S173, 2011). RESULTS: The results in both
      the groups did not reveal a significant difference in the clinical outcome
      assessment of back pain score or ODI. With the Wilcoxon two-sample test, no
      difference in median values was achieved (p value 0.0787 for ODI and p value
      0.1926 for back pain). The average ODI in the Wallis group dropped from 50.93 to
      29.11. The average VAS for the Wallis group back pain dropped from 7.79 to 4.22.
      CONCLUSION: The Wallis implant is a safe medical device. This study revealed a
      reduction in pain and functional disability in patients treated with
      decompression surgery for lumbar stenosis, with or without Wallis. The Wallis
      group improved more, but it was not statistically significant. The risk of
      complications is lower than other interspinous devices.

PMID- 25073943
TI  - A 3D finite element model to investigate prosthetic interface stresses of
      different posterior tibial slope.
AB  - PURPOSE: Posterior tibial slope that is created during proximal tibial resection
      in total knee arthroplasty has emerged as an important factor in the mechanics of
      the knee joint and the surgical outcome. But the ideal degree of posterior tibial
      slope for recovery of the knee joint function and preventions of complications
      remains controversial and should vary in different racial groups. The objective
      of this paper is to investigate the effects of posterior tibial slope on contact
      stresses in the tibial polyethylene component of total knee prostheses. METHODS:
      Three-dimensional finite element analysis was used to calculate contact stresses
      in tibial polyethylene component of total knee prostheses subjected to a
      compressive load. The 3D finite element model of total knee prosthesis was
      constructed from the images produced by 3D scanning technology. Stresses in
      tibial polyethylene component were calculated with four different posterior
      tibial slopes (0 degrees , 3 degrees , 6 degrees  and 9 degrees ). RESULTS: The
      3D finite element model of total knee prosthesis we presented was well validated.
      We found that the stress distribution in the polythene as evaluated by the
      distributions of the von Mises stress, the maximum principle stress, the minimum
      principle stress and the Cpress were more uniform with 3 degrees  and 6 degrees 
      posterior tibial slopes than with 0 degrees  and 9 degrees  posterior tibial
      slopes. Moreover, the peaks of the above stresses and trends of changes with
      increasing degree of knee flexion were more ideal with 3 degrees  and 6 degrees 
      posterior slopes. CONCLUSIONS: The results suggested that the tibial component
      inclination might be favourable to 7 degrees -10 degrees  so far as the stress
      distribution is concerned. The range of the tibial component inclination also can
      decrease the wear of polyethylene. Chinese posterior tibial slope is bigger than
      in the West, and the current domestic use of prostheses is imported from the
      West, so their demands to tilt back bone cutting can lead to shorten the service
      life of prostheses; this experiment result is of important clinical significance,
      guiding orthopaedic surgeon after the best angle to cut bone.

PMID- 25073944
TI  - A biomechanical assessment of a novel double endobutton technique versus a
      coracoid cerclage sling for acromioclavicular and coracoclavicular injuries.
AB  - PURPOSE: Recently, many acromioclavicular-coracoclavicular (AC-CC) ligament
      reconstruction techniques address only the CC ligament. However, many of these
      techniques are costly, time-consuming, and require the use of allogenic grafts,
      making them prone to creep and failure or novel devices making them challenging
      for orthopaedic surgeons. The purpose of this study was to compare the
      biomechanical characteristics of a double endobutton technique using a standard
      endobutton CL with those of a coracoid cerclage sling (CS) for reconstruction of
      the CC ligaments. METHODS: Anterior-posterior (AP) translation and superior
      inferior (SI) translation were quantified for eight matched pairs of intact AC
      joints. One shoulder from each pair underwent a double endobutton repair, using
      an endobutton CL modified with an additional endobutton (Smith & Nephew, Memphis,
      Tenn) and placed through holes in the coracoid and clavicle. The contra-lateral
      shoulder received a coracoid sling reconstruction using an anterior tibialis
      tendon. Translation testing was repeated after reconstruction, followed by load
      to-failure testing. Paired t tests were used for statistical analysis. RESULTS:
      The CS technique demonstrated a greater SI and AP translation than the double
      endobutton technique (p < 0.05). Additionally, the double endobutton technique
      had a greater stiffness (40.2 +/- 11.0 vs. 20.3 +/- 6.4 N/mm, p = 0.005), yield
      load (168.5 +/- 11.0 vs. 86.8 +/- 22.9 N, p = 0.002), and ultimate load (504.4 +/
      199.7 vs. 213.2 +/- 103.4 N, p = 0.026) when compared to the CS technique.
      CONCLUSION: The double endobutton technique yielded less translation about the AC
      joint and displayed stronger load-to-failure characteristics than the CS
      reconstruction. As such, this technique may be better suited to restore native AC
      CC biomechanics, reduce post-operative pain, and prevent recurrent subluxation
      and dislocation than an allogenic graft construct. The double endobutton
      technique may be a suitable option for addressing AC-CC injuries.

PMID- 25073945
TI  - Arthroscopic evaluation of persistent pain following supramalleolar osteotomy for
      varus ankle osteoarthritis.
AB  - PURPOSE: The purposes of this study were to investigate pain experienced by
      patients after supramalleolar osteotomy for varus ankle osteoarthritis and to
      analyse correlations between this pain and arthroscopic findings. METHODS: Twenty
      nine patients (31 ankles) who underwent arthroscopic evaluation after
      supramalleolar osteotomy were reviewed retrospectively. The visual analog scale
      (VAS) was used to assess pain, and the patients were instructed to record the
      time point, location, and character of the pain. The tibial-ankle surface angle,
      talar tilt, and tibial-lateral surface angle were measured on radiographs.
      RESULTS: The location, time point, and character of the pain experienced by the
      patients changed after supramalleolar osteotomy. The mean VAS score was
      significantly improved after supramalleolar osteotomy at the time of the
      arthroscopic evaluation (P < 0.001) and improved further after the arthroscopic
      procedures (P = 0.026). During arthroscopy, pathologic lesions such as adhesions,
      synovitis, and soft-tissue impingement were identified. A significant correlation
      was found between adhesions and dull pain and pain at rest (P = 0.016 and P =
      0.005, respectively). In addition, soft-tissue impingement in the lateral gutter
      was significantly correlated with dull pain, pain at rest, and clicking pain (P =
      0.001, P = 0.035, and P = 0.042, respectively). No significant correlations were
      found between post-operative radiographic measurements and development of
      pathologic lesions. CONCLUSIONS: With the use of arthroscopy, persistent pain
      experienced after supramalleolar osteotomy was found to be associated with
      adhesions, synovitis, and soft-tissue impingement in medial and lateral gutters
      of the ankle. Arthroscopy can be helpful in identifying and treating painful
      lesions commonly seen after supramalleolar osteotomy. An understanding of these
      painful lesions will help patients have more realistic expectations regarding the
      supramalleolar osteotomy. LEVEL OF EVIDENCE: Case series study, Level IV.

PMID- 25073947
TI  - Fusion guidance in endovascular peripheral artery interventions: a feasibility
      study.
AB  - PURPOSE: This study was designed to evaluate the feasibility of endovascular
      guidance by means of live fluoroscopy fusion with magnetic resonance angiography
      (MRA) and computed tomography angiography (CTA). METHODS: Fusion guidance was
      evaluated in 20 endovascular peripheral artery interventions in 17 patients.
      Fifteen patients had received preinterventional diagnostic MRA and two patients
      had undergone CTA. Time for fluoroscopy with MRA/CTA coregistration was recorded.
      Feasibility of fusion guidance was evaluated according to the following criteria:
      for every procedure the executing interventional radiologists recorded whether 3D
      road-mapping provided added value (yes vs. no) and whether PTA and/or stenting
      could be performed relying on the fusion road-map without need for diagnostic
      contrast-enhanced angiogram series (CEAS) (yes vs. no). Precision of the fusion
      road-map was evaluated by recording maximum differences between the position of
      the vasculature on the virtual CTA/MRA images and conventional angiography.
      RESULTS: Average time needed for image coregistration was 5 +/- 2 min. Three
      dimensional road-map added value was experienced in 15 procedures in 12 patients.
      In half of the patients (8/17), intervention was performed relying on the fusion
      road-map only, without diagnostic CEAS. In two patients, MRA roadmap showed a
      false-positive lesion. Excluding three patients with inordinate movements, mean
      difference in position of vasculature on angiography and MRA/CTA road-map was
      1.86 +/- 0.95 mm, implying that approximately 95 % of differences were between 0
      and 3.72 mm (2 +/- 1.96 standard deviation). CONCLUSIONS: Fluoroscopy with
      MRA/CTA fusion guidance for peripheral artery interventions is feasible. By
      reducing the number of CEAS, this technology may contribute to enhance procedural
      safety.

PMID- 25073946
TI  - Basal and stress-inducible expression of HSPA6 in human keratinocytes is
      regulated by negative and positive promoter regions.
AB  - Epidermal keratinocytes serve as the primary barrier between the body and
      environmental stressors. They are subjected to numerous stress events and are
      likely to respond with a repertoire of heat shock proteins (HSPs). HSPA6
      (HSP70B') is described in other cell types with characteristically low to
      undetectable basal expression, but is highly stress induced. Despite this
      response in other cells, little is known about its control in keratinocytes. We
      examined endogenous human keratinocyte HSPA6 expression and localized some
      responsible transcription factor sites in a cloned HSPA6 3 kb promoter. Using
      promoter 5' truncations and deletions, negative and positive regulatory regions
      were found throughout the 3 kb promoter. A region between -346 and -217 bp was
      found to be crucial to HSPA6 basal expression and stress inducibility. Site
      specific mutations and DNA-binding studies show that a previously uncharacterized
      AP1 site contributes to the basal expression and maximal stress induction of
      HSPA6. Additionally, a new heat shock element (HSE) within this region was
      defined. While this element mediates increased transcriptional response in
      thermally stressed HaCaT keratinocytes, it preferentially binds a stress
      inducible factor other than heat shock factor (HSF)1 or HSF2. Intriguingly, this
      newly characterized HSPA6 HSE competes HSF1 binding a consensus HSE and binds
      both HSF1 and HSF2 from other epithelial cells. Taken together, our results
      demonstrate that the HSPA6 promoter contains essential negative and positive
      promoter regions and newly identified transcription factor targets, which are key
      to the basal and stress-inducible expression of HSPA6. Furthermore, these results
      suggest that an HSF-like factor may preferentially bind this newly identified
      HSPA6 HSE in HaCaT cells. 

PMID- 25073948
TI  - Commentary on: centrifugal pump performance during low-flow extracorporeal CO2
      removal; safety considerations.

PMID- 25073949
TI  - Perfusionist techniques of reducing acute kidney injury following cardiopulmonary
      bypass: an evidence-based review.
AB  - Cardiac surgery utilizing cardiopulmonary bypass has come a long way since its
      introduction nearly 60 years ago. In the early days, end-organ damage was linked
      to contact of the blood with the extracorporeal circuit. One potential cardiac
      surgery complication known to result in significant morbidity and mortality is
      acute kidney injury (AKI). Causes of AKI are multifaceted, but most of them are
      associated with techniques that perfusionists employ during extracorporeal
      circuit management. These can cause patients to either go on dialysis or renal
      replacement therapy. Patients with AKI have longer lengths of stay and consume
      significant resources beyond those with normal kidney function. Few current
      evidence-based markers determine if the kidneys are adequately protected during
      surgery. Most relevant literature does not address perfusion-specific techniques
      that reduce the incidence of AKI. This paper reviews the pathophysiology of the
      kidney and focuses on perfusion techniques that may reduce the incidence of AKI. 

PMID- 25073950
TI  - Chemical interactions between plants in Mediterranean vegetation: the influence
      of selected plant extracts on Aegilops geniculata metabolome.
AB  - Allelopathy is the chemical mediated communication among plants. While on one
      hand there is growing interest in the field, on the other hand it is still
      debated as doubts exist at different levels. A number of compounds have been
      reported for their ability to influence plant growth, but the existence of this
      phenomenon in the field has rarely been demonstrated. Furthermore, only few
      studies have reported the uptake and the effects at molecular level of the
      allelochemicals. Allelopathy has been reported on some plants of Mediterranean
      vegetation and could contribute to structuring this ecosystem. Sixteen plants of
      Mediterranean vegetation have been selected and studied by an NMR-based
      metabolomics approach. The extracts of these donor plants have been characterized
      in terms of chemical composition and the effects on a selected receiving plant,
      Aegilops geniculata, have been studied both at the morphological and at the
      metabolic level. Most of the plant extracts employed in this study were found to
      have an activity, which could be correlated with the presence of flavonoids and
      hydroxycinnamate derivatives. These plant extracts affected the receiving plant
      in different ways, with different rates of growth inhibition at morphological
      level. The results of metabolomic analysis of treated plants suggested the
      induction of oxidative stress in all the receiving plants treated with active
      donor plant extracts, although differences were observed among the responses.
      Finally, the uptake and transport into receiving plant leaves of different
      metabolites present in the extracts added to the culture medium were observed.

PMID- 25073951
TI  - Diterpenes and phenolic compounds from Sideritis pullulans.
AB  - Phytochemical investigation of Sideritis pullulans aerial part and root extracts
      allowed to isolate six ent-kaurane diterpenes, two phenylpropanoids, and one
      coumarin, identified as 1alpha,3alpha,7beta,18-tetrahydroxy-ent-kaur-16-ene
      (sideripullol A) (1), 3alpha,11alpha,18-trihydroxy-ent-kaur-16-ene (sideripullol
      B) (2), 3alpha,7beta,18-trihydroxy-17-nor-ent-kauran-16-one (sideritone A) (3),
      3alpha,7beta-dihydroxy-18-acetyloxy-17-nor-ent-kauran-16-one (sideritone B) (4),
      3alpha,7beta,16alpha,17-tetrahydroxy-18-acetyloxy-ent-kaurane (sideripullol C)
      (5), 7beta,16alpha,17,18-tetrahydroxy-ent-kaurane (sideripullol D) (6), beta-(3
      methoxy-4-hydroxyphenyl)-ethyl-O-alpha-l-arabinopiranosyl-(1->2)-alpha-l
      rhamnopyranosyl-(1->3)-6-O-t-feruloyl-beta-d-glucopyranoside (sideritiside A)
      (7), beta-(3,4-dihydroxyphenyl)-ethyl-O-alpha-l-arabinopiranosyl-(1->2)-alpha-l
      rhamnopyranosyl-(1->3)-6-O-t-feruloyl-beta-d-glucopyranoside (sideritiside B)
      (8), and 7-demethyl-8-methoxycoumarsabin (9), respectively. Twenty known
      compounds, including phenolics, flavonol glycosides, iridoids, diterpenes,
      sesquiterpenes, lignans, coumarins, and phenylpropanoids were also isolated and
      characterized. All diterpenes were evaluated for their cytotoxic activity.

PMID- 25073952
TI  - [Heavy users of inpatient services: a comparison of diagnostic subgroups].
AB  - OBJECTIVE: Quantitative and qualitative assessment of heavy users (HU) of
      psychiatric inpatient treatment. METHODS: Screening over 9 months for patients
      with >= 3 admissions or >= 100 days of treatment during 1 year prior to index
      admission. RESULTS: During the recruiting period 1217 persons were treated of
      whom 132 (10.8 %) fulfilled HU criteria. Patients belonged most often to the
      diagnostic group F2 (43 %), followed by F1 (21 %) and F3 (17 %). HU were most
      common within the diagnostic group F6 (33 %), next to F2 (21 %), F1 (9 %) and F3
      (6 %). HU had signs of more severe illness compared to the other patients: only 8
      % held a job and 73 % ware on a disablement pension, patients with a diagnosis of
      F2 faring worst. HU were treated more frequently involuntarily (50.5 vs 30.7 %).
      An office-based physician referred only 5 % of the patients and almost half
      attended the clinic without any referral. HU participated only to a modest degree
      in community-based treatments and 37 % attended no doctor in the month prior to
      admission. During the year following the index admission more than 80 % of HU
      were admitted again and were hospitalized almost as many days as before the index
      admission. Patients with a diagnosis of F1 and F2 showed the greatest persistence
      of heavy use behavior. CONCLUSIONS: This sample of HU show a persistent pattern
      of use of psychiatric inpatient treatment. Strategies to improve the situation
      are discussed.

PMID- 25073953
TI  - Colocalization of beta-catenin with Notch intracellular domain in colon cancer: a
      possible role of Notch1 signaling in activation of CyclinD1-mediated cell
      proliferation.
AB  - The Wnt and Notch1 signaling pathways play major roles in intestinal development
      and tumorigenesis. Sub-cellular localization of beta-catenin has been implicated
      in colorectal carcinogenesis. However, the beta-catenin and Notch intracellular
      domain (NICD) interaction has to be addressed. Immunohistochemistries of beta
      catenin, NICD, and dual immunofluorescence of beta-catenin and NICD were analyzed
      in colorectal tissues and HT29 cell line. Moreover, real-time PCR analysis of
      CyclinD1, Hes1 and MUC2 was done in HT29 cells upon N-[N-(3, 5
      difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) treatment.
      Dual staining emphasized the strong interaction of beta-catenin and NICD in
      adenoma and adenocarcinoma than in normal tissues. Hes1 transcript levels were
      decreased 1.5- and 7.1-fold in 12.5 and 25 uM DAPT-treated HT29 cells. CyclinD1
      transcript levels decreased 1.2- and 1.6-fold, and MUC2 transcript level
      increased 4.3- and 7.5-fold in 12.5 and 25 uM DAPT-treated HT29 cells. The
      results of this study showed that the sub-cellular localization of beta-catenin
      converges with NICD inducing proliferation through the activation of CyclinD1 and
      Hes1. Moreover, the inhibition of Notch1 signaling by DAPT leads to the arrest of
      cell proliferation and induces apoptosis leading to the upregulation of MUC2, a
      secretory cell lineage marker. 

PMID- 25073954
TI  - A phase I study of combination therapy with nanoparticle albumin-bound paclitaxel
      and cyclophosphamide in patients with metastatic or recurrent breast cancer.
AB  - BACKGROUND: The objective of the present clinical study is to determine the
      maximum tolerated dose (MTD)/recommended dose (RD) of combination therapy with
      nanoparticle albumin-bound paclitaxel (nab-PTX) and cyclophosphamide (CPA) in
      patients with metastatic or recurrent breast cancer. METHODS: nab-PTX and CPA
      were administered on the first day of each 21-day treatment cycle. The dose of
      CPA was fixed at 600 mg/m(2), while the dose of nab-PTX was increased from 180
      mg/m(2) (Level 1) to 220 mg/m(2) (Level 2) and then to 260 mg/m(2) (Level 3).
      RESULTS: A total of 11 patients from two institutions were enrolled in the
      present study. At Level 3, a dose-limiting toxicity (DLT) was observed in 1
      patient. Considering treatment continuity and the risk of adverse events in Cycle
      2 and thereafter at this level, further subject enrollment at Level 3 was
      discontinued after two patients had been enrolled. Since the doses used at Level
      3 were considered the MTD of nab-PTX and CPA and the doses used at Level 2 were
      considered the RD of nab-PTX and CPA, three additional subjects were enrolled at
      Level 2. No DLTs were observed at Level 2. CONCLUSION: The RD of combination
      therapy with nab-PTX and CPA was 220 mg/m(2) and 600 mg/m(2), respectively, in
      patients with metastatic or recurrent breast cancer.

PMID- 25073955
TI  - Clinical results of definitive-dose (50 Gy/25 fractions) preoperative
      chemoradiotherapy for unresectable esophageal cancer.
AB  - BACKGROUND: The clinical results of definitive-dose preoperative
      chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal
      cancer were analyzed. METHODS: Inclusion criteria were unresectable esophageal
      squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the
      trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined
      concurrently with two courses of FP therapy (CDDP 70 mg/m(2) + 5-FU 700 mg/m(2)/d
      * 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after
      completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. RESULTS:
      Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were
      enrolled between 2008 and 2011. The clinical stages according to the 7th edition
      of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3,
      3/25/1/1. All 30 patients completed RT of 50 Gy/25 fractions. Initial tumor
      responses were 21 patients with resectable disease, 7 with unresectable disease,
      and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%)
      of the 30 patients. Pathological complete response was obtained in five (28%)
      patients. There were two patients with hospitalization death after surgery (11%).
      Six of the 7 patients who still had unresectable disease were treated with 1-3
      courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery
      showed long-term survival. The 3-year loco-regional control rate and the 3-year
      overall survival rate for the 30 patients were 70 and 49%, respectively.
      CONCLUSIONS: Definitive-dose preoperative CRT was feasible, and is a promising
      treatment strategy for unresectable esophageal cancer.

PMID- 25073957
TI  - Introduction to the "GRG profiles and perspectives" series.

PMID- 25073958
TI  - The state of research in Europe and in Italy: the risks of short-sighted
      decisions.
AB  - Research is facing declining funding rates everywhere, affecting the cultural and
      economic growth of some of major world powers. We looked at the choices on
      funding allocation made by the USA and by Europe, to compare priorities and
      analyze consequences. Also, within Europe, we focused on Italy and on its
      consistent brain-drain phenomenon, as an example of short-sighted research
      policies that appear to require not only the urgent infusion of monetary
      resources and the creation of new job opportunities, but also and especially a
      general change of cultural approach. 

PMID- 25073956
TI  - Finding sessile serrated adenomas: is it possible to identify them during
      conventional colonoscopy?
AB  - BACKGROUND AND AIM: Proximal colorectal cancer may arise from sessile serrated
      adenomas (SSAs). Recognition of these lesions during colonoscopy can optimize the
      endoscopic approach. We aimed to identify specific endoscopic features of SSA
      with conventional colonoscopy. METHODS: Patients undergoing screening
      colonoscopies from January 2011 to September 2012, in whom colonic polyps were
      found, were prospectively included in our study. Polyp morphology, location,
      polyp pit pattern (Kudo classification), and other previously reported features
      of SSA were evaluated. Histological examination was conducted independently by
      two pathologists. Multivariate analysis was performed to identify independent
      predictors of SSA. RESULTS: A total of 272 patients were included, and 440 polyps
      were evaluated (1.6 polyps per patient). Thirty-four polyps (8%) were SSA, 135
      (31%) hyperplastic, and 249 (56%) adenomas. The most prevalent endoscopic
      features of SSA were right-side location (94%), type II Kudo pit pattern (91%),
      mucus cap (41%), flat morphology (29%) and red-colored surface (26%).
      Multivariate analysis revealed that flat morphology (p = 0.002, OR = 3.81 CI 1.53
      9.09), red-colored surface (p < 0.001, OR = 12.97 CI 4.43-37.69), right-side
      location (p < 0.001, OR = 22.21 CI 5.09-135.94) and mucus cap (p < 0.001, OR 8.77
      CI 3.76-20.44) were independent predictors of SSA. CONCLUSION: We were able to
      identify specific features of SSA during conventional colonoscopy, which may help
      to identify, and therefore to optimize the endoscopic approach of these lesions.

PMID- 25073959
TI  - Apolipoprotein polymorphism is associated with pro-thrombotic profile in non
      demented dyslipidemic subjects.
AB  - Apolipoprotein gene polymorphism has an important role in lipid metabolism and in
      the development of cerebro- and cardio-vascular disease (CCVD), including
      dementia. Dyslipidemia and hemostatic abnormalities are key risk factors
      associated with athero-sclerotic events preceding CCVD. The aim of this study was
      to evaluate the possible relationships of various apolipoprotein-species with
      hemostatic parameters and cognitive function. Lipid profile, gene polymorphism,
      coagulation markers, and mini-mental state examination (MMSE) scores were
      assessed in 109 dys-lipidemic subjects and in 107 healthy control volunteers.
      Thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels were
      significantly higher in apolipoprotein-E2 (apoE2) patients when compared to other
      apoE forms. The apoA5 -1131T>C polymorphism was associated with elevated D-dimer
      concentration in dyslipidemic TT homozygous individuals. MMSE did not correlate
      with lipid or coagulation profile. These data suggest that apoE and apoA5
      variants have an effect on hemostatic parameters, but they neither influence nor
      predict cognitive performance in non-demented individuals. 

PMID- 25073960
TI  - Modulation of both activator protein-1 and nuclear factor-kappa B signal
      transduction of human T cells by amiodarone.
AB  - Amiodarone, a common and effective antiarrhythmic drug, has been reported to have
      anti-inflammatory effects such as reducing the activation and movement of
      neutrophils. However, its effects on human T cells remain unclear. The aim of
      this study was to elucidate the effects and possible underlying mechanisms of
      amiodarone on human T cells. We isolated human primary T cells from the
      peripheral blood of healthy volunteers and performed enzyme-linked immunosorbent
      assay (ELISA), flow cytometry, electrophoretic mobility shift assay, luciferase
      assay, and Western blotting to evaluate the modulatory effects of amiodarone on
      human T cells. We found that amiodarone dose dependently inhibited the production
      of cytokines, including interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha,
      and interferon-gamma in activated human T cells. By flow cytometry, we
      demonstrated that amiodarone suppressed the expression of IL-2 receptor-alpha
      (CD25) and CD69, the cell surface markers of activated T cells. Moreover,
      molecular investigations revealed that amiodarone down-regulated activator
      protein-1 (AP-1) and nuclear factor kappa-B (NF-kappaB) DNA-binding activities in
      activated human T cells and also inhibited DNA binding and transcriptional
      activities of both AP-1 and NF-kappaB in Jurkat cells. Finally, by Western
      blotting, we showed that amiodarone reduced the activation of c-Jun NH(2)
      terminal protein kinase and P38 mitogen-activated protein kinase, and suppressed
      stimuli-induced I-kappa B-alpha degradation in activated human T cells. Through
      regulation of AP-1 and NF-kappaB signaling, amiodarone inhibits cytokine
      production and T cell activation. These results show the pleiotropic effects of
      amiodarone on human T cells and suggest its therapeutic potential in inflammation
      related cardiovascular disorders.

PMID- 25073963
TI  - HPV16-related pigmented Bowen's disease on the palm.

PMID- 25073961
TI  - Expression of blood serum proteins and lymphocyte differentiation clusters after
      chronic occupational exposure to ionizing radiation.
AB  - This study aimed to assess effects of chronic occupational exposure on immune
      status in Mayak workers chronically exposed to ionizing radiation (IR). The study
      cohort consists of 77 workers occupationally exposed to external gamma-rays at
      total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure
      (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation
      from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control
      group consists of 43 age- and sex-matched individuals who never were exposed to
      IR, never involved in any cleanup operations following radiation accidents and
      never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry
      were used to determine the relative concentration of lymphocytes and proteins.
      The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were
      decreased in external gamma-exposed workers relative to control. Relative
      concentrations of NKT-lymphocytes, concentrations of transforming growth factor
      beta, interferon gamma, immunoglobulins A, immunoglobulins M and matrix
      proteinase-9 were higher in this group as compared with control. Relative
      concentrations of T-lymphocytes and concentration of interleukin-8 were
      decreased, while both the relative and absolute concentration of natural killers,
      concentration of immunoglobulins A and M and matrix proteinase-9 were increased
      in workers with combined exposure as compared to control. An inverse linear
      relation was revealed between absolute concentration of T-lymphocytes, relative
      and absolute concentration of T-helpers cells, concentration of interferon gamma
      and total absorbed dose from external gamma-rays in exposed workers. For workers
      with incorporated plutonium, there was an inverse linear relation of absolute
      concentration of T-helpers as well as direct linear relation of relative
      concentration of NKT-lymphocytes to total absorbed red bone marrow dose from
      internal alpha-radiation. In all, chronic occupational IR exposure of workers
      induced a depletion of immune cells in peripheral blood of the individuals
      involved.

PMID- 25073962
TI  - Improved bottom-up strategy to efficiently separate hypermodified histone
      peptides through ultra-HPLC separation on a bench top Orbitrap instrument.
AB  - Histone post-translational modifications (hPTMs) play a crucial role in
      modulating chromatin structure and enforcing specific functional states on the
      underlying genome. Through the design of ad hoc analytical methods, MS has
      contributed significantly in the dissection of hPTMs, exhibiting specific
      strengths in identifying novel marks and assessing their combinatorial interplay.
      However, the comprehensive analysis of all individual isoforms of some
      hypermodified histone regions remains highly challenging with conventional
      proteomics platforms. Since complex hPTM patterns have unique functional outcomes
      on the genes, the implementation of new MS-proteomics solutions can boost
      epigenetic research. Here, we assessed the effectiveness of a new analytical
      platform-which combines ultra high-performance LC (UHPLC) with high-resolution
      MS/MS analysis-in dissecting hypermodified regions from macrophage core histones.
      We compared the resolving power of this configuration with a standard setup based
      on HPLC-MS/MS and focused on two case-study peptides, H3 (27-40) and H4 (4-17).
      We observed that the novel platform resolves a much larger set of distinct
      peptide isoforms; among them some were resolved for the first time. A
      comprehensive analysis of hPTMs from macrophages was then carried out at basal
      state and upon lipopolysaccharide induction, to profile their temporal change in
      bulk chromatin during the inflammatory response.

PMID- 25073964
TI  - Cheek fistula from the ectopic salivary gland: a variant of the oculo-auriculo
      vertebral spectrum.
AB  - OBJECTIVES/HYPOTHESIS: This study aimed to investigate the diagnosis and
      management of a distinct developmental deformity syndrome characterized by
      congenital cheek fistula, ectopic accessory parotid gland, and preauricular
      appendage. STUDY DESIGN: Retrospective study. METHODS: We analyzed the medical
      records, radiologic and histopathologic findings, and follow-up data for seven
      patients (four males) with a congenital cheek salivary fistula. Computed
      tomography, fistulography, and sialography had been performed for diagnosis.
      Surgical treatment effect was evaluated. RESULTS: The mean age of the patients
      was 8.1 years (range, 2-16 years). The distinctive clinical feature was a
      congenital skin orifice lateral to the commissure with saliva discharge during
      eating. The cheek fistulae were accompanied by ipsilateral preauricular
      appendages in all seven patients. The skin orifice connected to an ectopic gland
      anterior to the masseter and inferior to Stensen's duct. Parotid sialography
      demonstrated an intact Stensen's duct in all cases. Hypoplasia of the ipsilateral
      mandible could be observed in five cases. Excision of the ectopic gland, skin
      orifice, and fistula was performed in five cases resulting in optimal treatment
      outcomes with no recurrent or adverse events. CONCLUSIONS: A congenital saliva
      discharging fistula with an ectopic accessory parotid gland, ipsilateral
      preauricular appendage, and mandibular hypoplasia constitutes a rare
      developmental syndrome. Surgical excision can effectively treat congenital cheek
      salivary fistula. LEVEL OF EVIDENCE: 4.

PMID- 25073965
TI  - Identification of ANKK1 rs1800497 variant in schizophrenia: new data and meta
      analysis.
AB  - One functional polymorphism (rs1800497) within the ankyrin repeat and kinase
      domain containing-1 gene (ANKK1) was reported to be associated with
      schizophrenia, but results among different studies vary and conclusions remain
      controversial. The present study sought to clarify this potential association
      among a population of Han Chinese with early onset schizophrenia using a case
      control (396 patients and 399 controls) and family based study (103 trios). We
      then performed a meta-analysis (comprising 11 case-control and 2 family-based
      studies) based on the present literature. Results of the association study
      revealed no significant difference in allele and genotype frequencies between the
      cases and controls, and no significant transmission distortion was detected.
      Kaplan-Meier survival analysis showed that age at onset in schizophrenia was
      significantly associated with the rs1800497 polymorphism in female patients, but
      not in males. Female T allele carriers had a lower age at onset than those
      without T allele (log rank statistic chi(2) = 5.16, P = 0.023; corrected P =
      0.046). Meta-analysis results indicated that rs1800497 is not associated with
      schizophrenia in the overall population (P = 0.77 for the case-control studies; P
      = 0.06 for the family-based studies). Our results support the hypothesis that
      rs1800497 polymorphism is likely to have a modifying rather than causative effect
      on schizophrenia. These findings may represent a significant genetic clue for the
      etiology of schizophrenia in females, but further investigation is required to
      clarify the exact role of ANKK1 in the development of schizophrenia.

PMID- 25073966
TI  - The macrophage activation marker sCD163 is associated with changes in NAFLD and
      metabolic profile during lifestyle intervention in obese children.
AB  - BACKGROUND: Obesity is associated with metabolic derangement and non-alcoholic
      fatty liver disease (NAFLD). Macrophages are involved in liver inflammation and
      fibrosis, and soluble (s)CD163 is a macrophage activation marker. OBJECTIVES: To
      associate sCD163 with parameters of paediatric obesity and NAFLD, as well as
      changes in these parameters during lifestyle intervention. METHODS: We studied
      117 obese children during a 10-week lifestyle intervention; 71 completed the 12
      month follow-up. We recorded clinical and biochemical data, and performed liver
      ultrasonography. RESULTS: Baseline sCD163 was higher in children with elevated
      alanine transaminase (ALT) (2.3 +/- 0.7 vs. 2.0 +/- 0.6 mg L(-1), P = 0.03),
      steatosis (2.3 +/- 0.7 vs. 2.0 +/- 0.6 mg L(-1), P = 0.01) and high paediatric
      NAFLD fibrosis index (2.3 +/- 0.7 vs. 1.9 +/- 0.6 mg L(-1) , P = 0.03). Baseline
      sCD163 was independently associated with ALT, cholesterol and high-sensitivity C
      reactive protein (hs-CRP). The change in sCD163 during lifestyle intervention was
      associated with changes in ALT, homeostatic model assessment of insulin
      resistance (HOMA-IR), hs-CRP and cholesterol, and inversely associated with the
      change in high-density lipoprotein cholesterol. CONCLUSION: sCD163 was associated
      with markers of liver injury and metabolic parameters in obese children, and
      changes in these parameters during lifestyle intervention. This may suggest that
      activated macrophages play a role in NAFLD and sCD163 may serve as a marker of
      liver disease severity and treatment effect.

PMID- 25073968
TI  - Two doctors die from Ebola and lives of others under threat in West Africa.

PMID- 25073967
TI  - Making a decision about trial participation: the feasibility of measuring
      deliberation during the informed consent process for clinical trials.
AB  - BACKGROUND: Informed consent of trial participants is both an ethical and a legal
      requirement. When facing a decision about trial participation, potential
      participants are provided with information about the trial and have the
      opportunity to have any questions answered before their degree of 'informed-ness'
      is assessed, usually subjectively, and before they are asked to sign a consent
      form. Currently, standardised methods for assessing informed consent have tended
      to be focused on aspects of understanding and associated outcomes, rather than on
      the process of consent and the steps associated with decision-making. METHODS:
      Potential trial participants who were approached regarding participation in one
      of three randomised controlled trials were asked to complete a short
      questionnaire to measure their deliberation about trial participation. A total of
      136 participants completed the 10-item questionnaire (DelibeRATE) before they
      made an explicit decision about trial participation (defined as signing the
      clinical trial consent form). Overall DelibeRATE scores were compared and
      investigated for differences between trial consenters and refusers. RESULTS: No
      differences in overall DelibeRATE scores were identified. In addition, there was
      no significant difference between overall score and the decision to participate,
      or not, in the parent trial. CONCLUSIONS: To our knowledge, this is the first
      study to prospectively measure the deliberation stage of the informed consent
      decision-making process of potential trial participants across different
      conditions and clinical areas. Although there were no differences detected in
      overall scores or scores of trial consenters and refusers, we did identify some
      interesting findings. These findings should be taken into consideration by those
      designing trials and others interested in developing and implementing measures of
      potential trial participants decision making during the informed consent process
      for research. TRIAL REGISTRATION: International Standard Randomised Controlled
      Trial Number (ISRCTN) Register ISRCTN60695184 (date of registration: 13 May
      2009), ISRCTN80061723 (date of registration: 8 March 2010), ISRCTN69423238 (date
      of registration: 18 November 2010).

PMID- 25073969
TI  - Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2
      negative breast cancer.
AB  - BACKGROUND: Patients with luminal HER2-negative tumours have a favourable
      prognosis. However, there is a subpopulation in which poorer outcomes are
      obtained with endocrine therapy alone. This subpopulation is considered to
      benefit from chemotherapy. However, the significance of chemotherapy for those
      with luminal tumours has decreased due to recent changes in treatment strategies.
      Thus, it is often difficult to determine whether we should recommend chemotherapy
      to such patients in clinical practice. We investigated Ki67 expression, as a
      means of predicting the responses of luminal HER2-negative breast cancer patients
      to neo-adjuvant chemotherapy (NAC), in order to identify a subpopulation that
      would benefit from these treatments. METHODS: We enrolled 114 luminal HER2
      negative breast cancer patients undergoing surgery after NAC. Biomarkers were
      examined using biopsy specimens obtained prior to treatment, to avoid any
      chemotherapy-related effects. Chemotherapy effects were determined employing
      operative specimens and we defined pathological complete response (pCR) as
      invasive nest disappearance, based only on the primary breast tumour. We applied
      receiver operating characteristic curve analysis to data from our 114 patients,
      to investigate Ki67 expression as a predictor of pCR. RESULTS: The pCR rate was
      significantly higher for tumours with high Ki67 expression (p < 0.01) and all
      patients who obtained pCR remained recurrence-free during the median 58-month
      observation period. We identified 35% as the Ki67 cut-off value which
      distinguishes those with a pCR from other cases. Another dataset, comprised of
      196 patients with a median 29-month observation period, was recruited for
      validation. Disease-free survival was found to be significantly (p < 0.01) lower
      in the patients with tumours in which Ki67 expression was higher than 35%.
      CONCLUSION: Our results raise the possibility of the luminal HER2-negative
      subpopulation with Ki67 expression higher than 35% benefiting from chemotherapy,
      as evidenced by improved survival.

PMID- 25073970
TI  - Mental disorders in Bangladesh: a systematic review.
AB  - BACKGROUND: Mental disorders constitute a major public health problem globally
      with higher burden in low and middle-income countries. In Bangladesh,
      systematically-collected data on mental disorders are scarce and this leaves the
      extent of the problem not so well defined. We reviewed the literature on mental
      health disorders in Bangladesh to summarize the available data and identify
      evidence gaps. METHODS: We identified relevant literature on mental disorders
      within Bangladesh published between 1975 and October, 2013 through a systematic
      and comprehensive search. Relevant information from the selected articles was
      extracted and presented in tables. RESULTS: We identified 32 articles which met
      our pre-defined eligibility criteria. The reported prevalence of mental disorders
      varied from 6.5 to 31.0% among adults and from 13.4 to 22.9% among children. Some
      awareness regarding mental health disorders exists at community level. There is a
      negative attitude towards treatment of those affected and treatment is not a
      priority in health care delivery. Mental health services are concentrated around
      tertiary care hospitals in big cities and absent in primary care. CONCLUSIONS:
      The burden of mental disorders is high in Bangladesh, yet a largely unrecognized
      and under-researched area. To improve the mental health services in Bangladesh,
      further well-designed epidemiological and clinical research are needed.

PMID- 25073971
TI  - Global attentional neglect of segmented lines in Parkinson's disease.
AB  - Global attention requires disengagement from focal elements of stimuli. Since
      people with Parkinson's disease (PD) may reveal impaired disengagement, this
      study attempted to learn if people with PD may be impaired at allocating global
      attention. Healthy adults and people with PD attempted to bisect lines of uniform
      thickness and lines composed of two segments of unequal thickness and length.
      When the longer line segment was to the right of the shorter segment, the group
      with PD demonstrated an increased deviation toward the longer segment, supporting
      the postulate that people with PD have an impaired ability to disengage focal
      attention and engage global spatial attention. 

PMID- 25073973
TI  - Role of nucleotide excision repair and p53 in zidovudine (AZT)-induced
      centrosomal deregulation.
AB  - The nucleoside reverse transcriptase inhibitor zidovudine (AZT) induces genotoxic
      damage that includes centrosomal amplification (CA > 2 centrosomes/cell) and
      micronucleus (MN) formation. Here we explored these end points in mice deficient
      in DNA repair and tumor suppressor function to evaluate their effect on AZT
      induced DNA damage. We used mesenchymal-derived fibroblasts cultured from
      C57BL/6J mice that were null and wild type (WT) for Xpa, and WT,
      haploinsufficient and null for p53 (6 different genotypes). Dose-responses for CA
      formation, in cells exposed to 0, 10, and 100 MUM AZT for 24 hr, were observed in
      all genotypes except the Xpa((+/+)) p53((+/-)) cells, which had very low levels
      of CA, and the Xpa((-/-)) p53((-/-)) cells, which had very high levels of CA. For
      CA there was a significant three-way interaction between Xpa, p53, and AZT
      concentration, and Xpa((-/-)) cells had significantly higher levels of CA than
      Xpa((+/+)) cells, only for p53((+/-)) cells. In contrast, the MN and MN +
      chromosomes (MN + C) data showed a lack of AZT dose response. The Xpa((-/-))
      cells, with p53((+/+)) or ((+/-)) genotypes, had levels of MN and MN + C higher
      than the corresponding Xpa((+/+)) cells. The data show that CA is a major event
      induced by exposure to AZT in these cells, and that there is a complicated
      relationship between AZT and CA formation with respect to gene dosage of Xpa and
      p53. The loss of both genes resulted in high levels of damage, and p53
      haploinsufficicency strongly protected Xpa((+/+)) cells from AZT-induced CA
      damage.

PMID- 25073972
TI  - The transcription factor Ap-1 regulates monkey 20alpha-hydroxysteroid
      dehydrogenase promoter activity in CHO cells.
AB  - BACKGROUND: Monkey 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is a
      catabolic enzyme responsible for converting progesterone into biologically
      inactive 20alpha-hydroxyprogesterone, thereby playing a key role in the estrous
      cycle or pregnancy and allowing ovulation and parturition to occur in most
      mammalian animals. Monkey 20alpha-HSD was highly abundant in ovarian and
      placental tissues during the pre-ovulation and pre-parturition phase and was
      primarily localized in the syncytiotrophoblast of the placenta. In this study, we
      focused on the molecular characterization of the monkey 20alpha-HSD promoter
      region by conducting reporter assays in Chinese hamster ovary (CHO) K1 cells.
      RESULTS: A reporter assay using constructs of various lengths of the 5'-flanking
      region (-890-Luc, -513-Luc, -306-Luc, -273-Luc, and -70-Luc) revealed that a
      region corresponding to the activator protein 1 (Ap-1) located between -281 and 
      274 bp was essential for the transcriptional activity. Absence of the Ap-1 site
      in -273-Luc dramatically decreased the transcription levels to the control
      levels. When the reporter constructs were co-transfected with Ap-1 (Jun) and
      specificity protein (Sp-1) genes, the transcription activities of the constructs
      increased with the exception of -273 and -70, while that of the double construct
      was reduced compared to that of Ap-1 alone. Furthermore, mutational analysis
      demonstrated that a putative Ap-1 site played an important role in the expression
      of the reporter gene. These findings were confirmed by EMSA examining the
      interactions of the protein Ap-1 in a nuclear extract from CHO-K1 cells and the
      expression levels of the Ap-1 transcription factor in pre-parturition placenta
      and CHO-K1 cells. Although mut-1 and mut-2 of Ap-1 bound with nuclear extracts
      from CHO-K1 cells, the transcriptional activity of mut-3 was almost completely
      suppressed. CONCLUSIONS: Our results indicate that the Ap-1 site (-281 -> -274)
      (5'-TGTCTCAT-3') plays a crucial role in the activation of the monkey 20alpha-HSD
      gene. Thus, we demonstrated that monkey 20alpha-HSD promoter activity is
      regulated by the transcription factor Ap-1 in CHO-K1 cells.

PMID- 25073974
TI  - Tricuspid regurgitation in hypoplastic left heart syndrome: mechanistic insights
      from 3-dimensional echocardiography and relationship with outcomes.
AB  - BACKGROUND: Our purpose was to test the following hypotheses: (1) patients with
      hypoplastic left heart syndrome who develop significant tricuspid regurgitation
      (TR) or require tricuspid valve (TV) surgery in the medium term have detectable
      TV abnormalities by 3-dimensional echocardiography (3DE) prestage 1 palliation
      and (2) TR is associated with reduced survival and increased TV intervention.
      METHODS AND RESULTS: Infants were prospectively studied with 3DE and 2DE prestage
      1 and followed up for the end points of TR, TV surgery, transplantation, or
      death. From prestage 1 3DE, spatial coordinates of TV annulus and leaflets were
      extracted; annulus size, leaflet area, prolapse volume, tethering volume, bending
      angle, and papillary muscle angle were measured. TR was assessed prestage 1 and
      at latest follow-up. Of 70 patients, 62 (88.6%) had mild or less TR and 8 (11.4%)
      had moderate or greater TR prestage 1. Prestage 1 tethering volume correlated to
      leaflet area (r=0.736; P<0.001), annulus area (r=0.651; P<0.001), right
      ventricular end-diastolic area (r=0.347; P=0.003), fractional area change (r=
      0.387; P<0.001), and TR grade (r=0.447; P<0.001). At follow-up, 46 (65.7%) had
      mild or less TR (group A) and 24 (34.3%) had moderate or greater TR (group B).
      Prestage 1 3DE showed greater TV tethering volume and flatter annulus in group B.
      Survival was better in group A. CONCLUSIONS: Increased TV tethering volume and
      flatter bending angle prestage 1 palliation is associated with TV failure at
      medium-term follow-up. Increased prestage 1 tethering is related to having larger
      TV annulus, larger leaflet area, larger right ventricular size, and reduced
      systolic function. TR progression results in increased TV intervention and
      decreased survival.

PMID- 25073975
TI  - Paternal age and assisted reproductive outcomes in ICSI donor oocytes: is there
      an effect of older fathers?
AB  - STUDY QUESTION: Does paternal age affect semen quality and reproductive outcomes
      in oocyte donor cycles with ICSI? SUMMARY ANSWER: Paternal age is associated with
      a decrease in sperm quality, however it does not affect either pregnancy or live
      birth rates in reproductive treatments when the oocytes come from donors <36
      years old and ICSI is used. WHAT IS KNOWN ALREADY: The weight of evidence suggest
      that paternal age is associated with decreasing sperm quality, but uncertainty
      remains as to whether reproductive outcomes are affected. Although developed to
      treat severe sperm factor infertility, ICSI is gaining popularity and is often
      used even in the presence of mild male factor infertility. STUDY DESIGN, SIZE,
      DURATION: A retrospective cohort study spanning the period between February 2007
      and June 2010. A total of 4887 oocyte donation cycles were included.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Fertilization was carried out by ICSI
      in all cycles included, and the semen sample used was from the male partner in
      all cases. The association of male age with semen parameters (volume,
      concentration, percentage of motile spermatozoa) was analyzed by multiple
      analysis of covariance. The association of male age with reproductive outcomes
      (biochemical pregnancy, miscarriage, ongoing pregnancy and live birth rate) was
      modeled by logistic regression, where the following covariates were introduced:
      donor age, recipient age, semen state (fresh versus frozen) and number of
      transferred embryos (3 and 2 versus 1). MAIN RESULTS AND THE ROLE OF CHANCE: We
      identified a significant relationship between paternal age and all sperm
      parameters analyzed: for every 5 years of age, sperm volume decreases by 0.22 ml
      (P < 0.001), concentration increases by 3.1 million sperm/ml (P = 0.003) and
      percentage motile spermatozoa decreases by 1.2% (P < 0.001). No differences were
      found in reproductive outcomes (biochemical pregnancy, miscarriage, clinical
      pregnancy, ongoing pregnancy and live birth) among different male age groups.
      LIMITATIONS, REASONS FOR CAUTION: The use of donor oocytes, while extremely
      useful in highlighting the role of male age in reproductive outcomes, limits the
      generalization of our results to a population of young women with older male
      partners. No data were available on perinatal and obstetrical outcomes of these
      pregnancies. Most (75%) cycles used frozen/thawed sperm samples which might have
      introduced a bias owing to loss of viability after thawing. ICSI was performed in
      all cycles to control for fertilization method; this technique could mask the
      natural fertilization rate of poorer sperm samples. Furthermore, we did not use
      stringent ICSI indications; and our data are therefore not generalizable to cases
      where only severe male factor is considered. However, male patients were of
      different racial background, thus allowing generalizing our results to a wider
      patient base. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that
      paternal age does not affect reproductive outcomes when the oocyte donor is <36
      years of age, indicating that ICSI and oocyte quality can jointly overcome the
      lower reproductive potential of older semen. STUDY FUNDING/COMPETING INTERESTS:
      This study was supported in part by Fundacio Privada EUGIN. The authors have no
      conflicts of interest to declare.

PMID- 25073976
TI  - Optimizing MRI of small joints and extremities.
AB  - Obtaining optimal images of small joints using magnetic resonance imaging (MRI)
      can be technically challenging. The aim of this review is to outline the
      practical aspects of MRI of small joints, with reference to the underlying
      physical principles. Although the most important contribution to successful
      imaging of small joints comes from the magnet field strength and design of the
      receiver coil, there are a number of factors to balance including the signal-to
      noise ratio, image resolution, and acquisition times. We discuss strategies to
      minimize artefacts from movement, inhomogeneity, chemical shift, and fat
      suppression. As with all MRI, each strategy comes at a price, but the benefits
      and costs of each approach can be fine-tuned to each combination of joint,
      receiver coil, and MRI machine. 

PMID- 25073977
TI  - Vulnerability of Bacillus spores and of related genera to physical impaction
      injury with particular reference to spread-plating.
AB  - AIMS: To examine whether bacterial spores are vulnerable to impaction injury
      during standard spread-plating or to other modes of physical impaction. METHODS
      AND RESULTS: Employing heat-challenged spores of Bacillus pumilus, Bacillus
      subtilis, Bacillus thuringiensis, Lysinibacillus, Paenibacillus and Brevibacillus
      spp. from day-4 to day-10 nutrient agar (NA) plates in 50% ethanol, plating the
      spore suspension to the extent of just drying the agar surface on fresh NA (50-60
      s; SP-B) was tested in comparison with the spreader-independent approach of
      spotting-and-tilt-spreading (SATS), or a brief plating (<10 s; SP-A). Spore CFU
      was significantly reduced with SP-B in different organisms (23-40%) over SATS
      independent of the spore size. Comparing 4-, 7- and 10-day-old B. pumilus spores,
      the former two displayed significant CFU reduction in SP-B indicating a spore age
      related effect. Continuous plating for 2-5 min showed a reduction in spore CFU in
      all organisms depending on plating duration. CFU reduction effect with SP-B was
      less manifest on refrigerated plates where no friction was experienced but acute
      on prewarmed and surface-dried plates. Spreader movement over agar surface
      subsequent to the exhaustion of free moisture proved highly detrimental to
      spores. A simulated plating study by plating the spores over a plastic film till
      drying showed a significant reduction in spore CFU. DAPI staining and glass bead
      vortexing studies confirmed spore disruption through physical impaction.
      CONCLUSIONS: Bacterial spores are vulnerable to injury during spread-plating or
      with other forms of physical impaction with variable effects on different
      genotypes independent of the spore size but altered by spore age. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Implications during spore CFU estimations employing
      spread-plating and during spore surveillance, and the recommendation of SATS as
      an easier and safer alternative for spore CFU enumeration.

PMID- 25073978
TI  - Embryonic expression of EphA receptor genes in mice supports their candidacy for
      involvement in cleft lip and palate.
AB  - BACKGROUND: Eph receptors, comprising the A- and B-subfamilies, are the largest
      family of receptor tyrosine kinases in the mammalian genome, and their function
      is critical for morphogenesis in a variety of contexts. Whereas signaling through
      B-type Ephs has been demonstrated to play a role in cleft lip and palate (CL/P),
      the involvement of A-type Ephs has not been examined in this context
      notwithstanding a recent genome-wide association study that identified the EPHA3
      locus as a candidate for non-syndromic CL/P. RESULTS: Here, we present a
      systematic analysis of the gene expression patterns for the nine EphA receptors
      at progressive stages of mouse development and find that EphA3, EphA4, and EphA7
      exhibit restricted overlapping patterns of expression during palate development.
      We find that homozygous mutation of EphA3 or compound homozygous mutation of
      EphA3 and EphA4 in mice does not result in defective midfacial development,
      supporting the possibility of redundant function with EphA7. We also document
      previously undescribed expression patterns in other tissues of the craniofacial
      complex including the lacrimal duct and salivary glands. CONCLUSIONS: Together,
      these results are consistent with the hypothesis that mutations in EPHA family
      genes may cause CL/P and also suggest that functional redundancy between family
      members may be at play.

PMID- 25073979
TI  - Neuroimaging craving: urge intensity matters.
AB  - Functional neuroimaging has become an increasingly common tool for studying drug
      craving. Furthermore, functional neuroimaging studies, which have addressed an
      incredibly diverse array of questions regarding the nature and treatment of
      craving, have had a substantial impact on theoretical models of addiction. Here,
      we offer three points related to this sizeable and influential body of research.
      First, we assert that the craving most investigators seek to study represents not
      just a desire but a strong desire to use drugs, consistent with prominent
      theoretical and clinical descriptions of craving. Secondly, we highlight that,
      despite the clear conceptual and clinical emphasis on craving as an intense
      desire, brain imaging studies often have been designed explicitly in a way that
      reduces the ability to generate powerful cravings. We illustrate this point by
      reviewing the peak urge levels endorsed by participants in functional magnetic
      resonance imaging (fMRI) studies of cigarette craving in nicotine-deprived versus
      non-deprived smokers. Thirdly, we suggest that brain responses measured during
      mild states of desire (such as following satiety) differ in fundamental ways from
      those measured during states of overpowering desire (i.e. craving) to use drugs.
      We support this position by way of a meta-analysis revealing that fMRI cue
      exposure studies using nicotine-deprived smokers have produced different patterns
      of brain activation to those using non-deprived smokers. Regarding brain imaging
      studies of craving, intensity of the urges matter, and more explicit attention to
      urge intensity in future work has the potential to yield valuable information
      about the nature of craving. 

PMID- 25073980
TI  - ABC transporters are involved in defense against permethrin insecticide in the
      malaria vector Anopheles stephensi.
AB  - BACKGROUND: Proteins from the ABC family (ATP-binding cassette) represent the
      largest known group of efflux pumps, responsible for transporting specific
      molecules across lipid membranes in both prokaryotic and eukaryotic organisms. In
      arthropods they have been shown to play a role in insecticide defense/resistance.
      The presence of ABC transporters and their possible association with insecticide
      transport have not yet been investigated in the mosquito Anopheles stephensi, the
      major vector of human malaria in the Middle East and South Asian regions. Here we
      investigated the presence and role of ABCs in transport of permethrin insecticide
      in a susceptible strain of this mosquito species. METHODS: To identify ABC
      transporter genes we obtained a transcriptome from untreated larvae of An.
      stephensi and then compared it with the annotated transcriptome of Anopheles
      gambiae. To analyse the association between ABC transporters and permethrin we
      conducted bioassays with permethrin alone and in combination with an ABC
      inhibitor, and then we investigated expression profiles of the identified genes
      in larvae exposed to permethrin. RESULTS: Bioassays showed an increased mortality
      of mosquitoes when permethrin was used in combination with the ABC-transporter
      inhibitor. Genes for ABC transporters were detected in the transcriptome, and
      five were selected (AnstABCB2, AnstABCB3, AnstABCB4, AnstABCmember6 and
      AnstABCG4). An increased expression in one of them (AnstABCG4) was observed in
      larvae exposed to the LD50 dose of permethrin. Contrary to what was found in
      other insect species, no up-regulation was observed in the AnstABCB genes.
      CONCLUSIONS: Our results show for the first time the involvement of ABC
      transporters in larval defense against permethrin in An. stephensi and, more in
      general, confirm the role of ABC transporters in insecticide defense. The
      differences observed with previous studies highlight the need of further research
      as, despite the growing number of studies on ABC transporters in insects, the
      heterogeneity of the results available at present does not allow us to infer
      general trends in ABC transporter-insecticide interactions.

PMID- 25073981
TI  - Analytic parallel-polarized light imaging technique using various light-emitting
      diodes: a comparison with skin conductance values.
AB  - BACKGROUND: The quantitative difference of the light reflected from a skin
      surface can be analyzed using parallel-polarized light (PPL) photography when
      combined with an analytic technique similar to colorimetric photography.
      OBJECTIVE: To improve the PPL photography technique as an assessment tool for the
      evaluation of skin condition using light-emitting diodes (LED) of different
      colors. METHOD: Parallel-polarized light images were taken using white and green
      LED illuminators. The acquired images were transformed to CIELAB coordinates. An
      in-house skin conductance meter was constructed to assess skin hydration level. A
      dermatologist evaluated the clinical grading of dryness and glossiness. These
      clinical severities were also compared statistically with the CIELAB values.
      RESULTS: As with the green illuminator, the correlation analysis of whole sites
      showed that the L* value positively correlated with age (r = 0.18677, P < 0.05),
      and that the a* value has negative and positive relationships with age (r = 
      0.20528, P < 0.05) and glossiness (r = 0.20885, P < 0.05) respectively.
      CONCLUSION: The correlations between CIELAB values and multiple characteristics
      of skin were more significant when green LED was applied than when white light
      was applied. In addition, coherent relationships between the grade of dryness and
      skin conductance values showed that visual assessment could be appropriate for
      the study as with objective measurement.

PMID- 25073982
TI  - The surgical outcome of traumatic extra-axial hematomas causing brain herniation
      in children.
AB  - AIM: The aim of this study was to assess the surgical outcome and prognostic
      importance of clinical and radiological data from children operated on under
      emergency conditions due to an extra-axial hematoma causing brain herniation.
      METHODS: This retrospective study included 25 children operated on due to
      herniated traumatic extra-axial hematomas from January 2000 to December 2010.
      RESULTS: Of those 25 children, 17 (68%) were diagnosed with subdural hematoma
      (SDH), 7 (28%) with epidural hematoma (EDH) and only 1 patient (4%) suffered from
      both SDH and EDH. Overall mortality from a herniated extra-axial hematoma was
      44%. The mortality rate for herniated SDH patients was 52.9%, and only 1 patient
      died from a herniated EDH (14.2%). Low Glasgow coma scale scores at admission,
      high postoperative intracranial pressure (ICP) values, longer intervals from
      trauma to surgery, longer durations of brain herniation, the presence of
      intraoperative brain swelling, larger and thicker hematomas and more displacement
      of the midline structures and obliteration of the basal cisterns were all
      correlated with mortality and an unfavorable outcome. CONCLUSIONS: Brain
      herniation is a serious consequence of traumatic extra-axial hematomas in
      children, and approximately one third of these patients have the potential for a
      favorable outcome. We recommend postoperative ICP monitoring to predict outcome
      and early decompressive surgery when possible for promising results.

PMID- 25073984
TI  - The association of intensivists with failure-to-rescue rates in outlier
      hospitals: results of a national survey of intensive care unit organizational
      characteristics.
AB  - PURPOSE: Critical care is often an integral part of rescue for patients with
      surgical complications. We sought to understand critical care characteristics
      predictive of failure-to-rescue (FTR) performance at the hospital level. METHODS:
      Using 2009 to 2011 FTR data from Hospital Compare, we identified 144 outlier
      hospitals with significantly better/worse performance than the national average.
      We surveyed intensive care unit (ICU) directors and nurse managers regarding
      physical structures, patient composition, staffing, care protocols, and rapid
      response teams (RRTs). Hospitals were compared using descriptive statistics and
      logistic regression. RESULTS: Of 67 hospitals completing the survey, 56.1% were
      low performing, and 43.9% were high performing. Responders were more likely to be
      teaching hospitals (40.9% vs 25.0%; P=.05) but were similar to nonresponders in
      terms of size, region, ownership, and FTR performance. Poor performers were more
      likely to serve higher proportions of Medicaid patients (68.4% vs 20.7%; P<.0001)
      and be level 1 trauma centers (55.9% vs 25.9%; P=.02). After controlling for
      these 2 characteristics, an intensivist on the RRT (adjusted odds ratio, 4.27;
      confidence interval, 1.45-23.02; P=.005) and an internist on staff in the ICU
      (adjusted odds ratio, 2.13; P=.04) were predictors of high performance.
      CONCLUSIONS: Intensivists on the RRT and internists in the ICU may represent
      discrete organizational strategies for improving patient rescue. Hospitals with
      high Medicaid burden fare poorly on the FTR metric.

PMID- 25073985
TI  - Majority logic gate for 3D magnetic computing.
AB  - For decades now, microelectronic circuits have been exclusively built from
      transistors. An alternative way is to use nano-scaled magnets for the realization
      of digital circuits. This technology, known as nanomagnetic logic (NML), may
      offer significant improvements in terms of power consumption and integration
      densities. Further advantages of NML are: non-volatility, radiation hardness, and
      operation at room temperature. Recent research focuses on the three-dimensional
      (3D) integration of nanomagnets. Here we show, for the first time, a 3D
      programmable magnetic logic gate. Its computing operation is based on physically
      field-interacting nanometer-scaled magnets arranged in a 3D manner. The magnets
      possess a bistable magnetization state representing the Boolean logic states '0'
      and '1.' Magneto-optical and magnetic force microscopy measurements prove the
      correct operation of the gate over many computing cycles. Furthermore,
      micromagnetic simulations confirm the correct functionality of the gate even for
      a size in the nanometer-domain. The presented device demonstrates the potential
      of NML for three-dimensional digital computing, enabling the highest integration
      densities. 

PMID- 25073986
TI  - Socioeconomic dimensions of malaria and India's policy for its control and
      elimination.

PMID- 25073983
TI  - The importance of the one carbon cycle nutritional support in human male
      fertility: a preliminary clinical report.
AB  - BACKGROUND: Sperm chromatin structure is often impaired; mainly due to oxidative
      damage. Antioxidant treatments do not consistently produce fertility improvements
      and, when given at high doses, they might block essential oxidative processes
      such as chromatin compaction. This study was intended to assess the effect on
      male sub-fertility of a pure one carbon cycle nutritional support without strong
      antioxidants. METHODS: Male partners of couples resistant to at least 2 assisted
      reproductive technology (ART) attempts, with no evidence of organic causes of
      infertility and with either DNA fragmentation index (DFI) measured by Terminal
      deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) or nuclear
      decondensation index (SDI) measured by aniline blue staining exceeding 20%, were
      invited to take part in a trial of a nutritional support in preparation for a
      further ART attempt. The treatment consisted of a combination of B vitamins,
      zinc, a proprietary opuntia fig extract and small amounts of N-acetyl-cysteine
      and Vitamin E (CondensylTM), all effectors of the one carbon cycle. RESULTS: 84
      patients were enrolled, they took 1 or 2 CondensylTM tablets per day for 2 to 12
      months. Positive response rates were 64.3% for SDI, 71.4% for DFI and 47.6% for
      both SDI and DFI. Eighteen couples (21%) experienced a spontaneous pregnancy
      before the planned ART cycle, all ended with a live birth. The remaining 66
      couples underwent a new ART attempt (4 IUI; 18 IVF; 44 ICSI) resulting in 22
      further clinical pregnancies and 15 live births. The clinical pregnancy rate
      (CPR) and the live birth rate (LBR) were 47.6% and 39.3% respectively. The full
      responders, i.e. the 40 patients achieving an improvement of both SDI and DFI,
      reported a CPR of 70% and a LBR of 57.5% (p<0.001). CONCLUSIONS: Nutritional
      support of the one carbon cycle without strong antioxidants improves both the SDI
      and the DFI in ART resistant male partners and results in high pregnancy rates
      suggesting a positive effect on their fertility potential.

PMID- 25073987
TI  - Attitude and knowledge of healthcare workers in critical areas towards deceased
      organ donation in a public sector hospital in India.
AB  - BACKGROUND: The attitude of healthcare workers towards organ donation can either
      facilitate or hinder the process of organ donation. We assessed the attitude of
      healthcare workers employed in intensive or emergency care units of our hospital
      towards organ donation, and the influence of various factors on willingness for
      self-organ donation after death. METHODS: All doctors, paramedical workers,
      nursing staff and other staff members working in six distinct intensive or
      emergency care units in the hospital were requested to fill a completely
      anonymous, voluntary and self-administered questionnaire. Younger individuals,
      women and nurses constituted a majority of the study population. RESULTS: The
      questionnaire completion rate was 99%. About 55% of the study population were
      agreeable to donating organs after death and 27% were undecided. The factors that
      positively influenced their willingness to donate organs after death were
      favourable attitude of the spouse, religious beliefs supporting organ donation,
      knowledge of hospital's organ transplant programme, personal experience of the
      organ donation scenario, having ever donated blood or involvement in social
      activities, willingness to become an eye donor and willingness to become a living
      kidney donor. CONCLUSION: A largely favourable attitude towards organ donation
      was seen in our study population. However, the study reflects incomplete
      knowledge leading to confusion and thus, desire to know more among participants
      with respect to various aspects regarding organ donation. The factors identify
      that positively influence decisions regarding organ donation can be used as
      direct interventions.

PMID- 25073988
TI  - Role of FDG PET-CT in asymptomatic epithelial ovarian cancer with rising serum CA
      125: a pilot study.
AB  - BACKGROUND: We evaluated the role of 18F-fluorodeoxy glucose (FDG) PET-CT scan in
      the diagnosis of early relapse in patients with epithelial ovarian cancer (EOC)
      who were asymptomatic but had a rising serum CA-125 level. METHODS: Between May
      2006 and July 2008, 16 patients with advanced EOC (stages III and IV) who had
      achieved complete response after cytoreductive surgery and platinum-based
      chemotherapy were included. These patients were asymptomatic but had a rising
      serum CA-125 level with normal physical examination and contrast-enhanced CT scan
      of the abdomen and pelvis. Patients were evaluated with (18)F-FDG PET-CT scan.
      Written informed consent was taken. Patients with a positive PET-CT scan were
      advised ultrasound-guided fine-needle aspiration cytology (FNAC) from the area
      showing increased uptake. Patients in whom FNAC was negative or inconclusive or
      those with negative PET-CT scan were followed up closely for the next 6 months
      with repeat clinical evaluation and CT scan. RESULTS: Fifteen patients (15/16)
      had a positive PET-CT scan. In 9 patients the positive PET lesion was confirmed
      on FNAC, while in 5 patients this was confirmed on follow-up CT scan after 6
      months. One patient who had a single positive lesion in the pelvis on PET-CT was
      initially considered false-positive because a follow-up CT scan at 6 months did
      not show the lesion. However, on regular follow-up after 2 years, she was
      detected to have an isolated lesion in the PET-positive area which was confirmed
      on secondary cytoreduction. This patient was considered as true-positive in the
      current analysis. One patient, who had a negative PET-CT scan and a negative CT
      scan at 6 months' follow-up was considered true-negative. The sensitivity and
      specificity of PET-CT scan was 100%. We could confirm positivity on
      histopathology/FNAC in 10 of the 15 (66.7%) true-positive cases. CONCLUSION: 18F
      FDG PET-CT scan is a sensitive and specific technique for early diagnosis of
      relapse in asymptomatic EOC patients with rising CA-125. However, its role in the
      management of recurrent ovarian cancers needs further evaluation.

PMID- 25073989
TI  - Do patients with tuberculosis referred from a tertiary care referral centre reach
      their peripheral health institution?
AB  - BACKGROUND: Tuberculosis (TB) is a major public health problem in India. The
      Revised National Tuberculosis Control Programme (RNTCP), started in 1997,
      involved medical colleges in the control of TB on a high priority. We assessed
      whether patients with TB referred from a tertiary care hospital in Delhi reached
      the desired peripheral health institution and had their treatment initiated.
      METHODS: This descriptive, retrospective study was done at a tertiary care
      hospital and included all patients with a diagnosis of TB (pulmonary or
      extrapulmonary) who were seen at the referral centre during the year 2011. Data
      were collected from various records of the referral centre and analysed for
      availability of feedback of the referred patients. Information regarding their
      registration and initiation of treatment was also collected. Postcards were used
      for the first time to trace referrals in patients with TB. RESULTS: The majority
      (94%) of patients with TB seen in the referral centre at a tertiary care facility
      were referred to a peripheral health institution nearest to their place of
      residence. Feedback on referral was received from these institutions for 79.4% of
      patients from the National Capital Region (NCR) of Delhi and for 47.4% of
      patients from outside the NCR of Delhi. CONCLUSION: We found that a majority of
      patients with TB were referred and the registration and initiation of treatment
      could be traced in >75% of patients.

PMID- 25073990
TI  - A community-based study of menstrual hygiene practices and willingness to pay for
      sanitary napkins among women of a rural community in northern India.
AB  - BACKGROUND: Hygiene-related practices of women during menstruation are of
      paramount importance. There is a lack of sizeable literature on menstrual
      practices from northern India. We documented the menstrual hygiene practices of
      rural women and assessed their willingness to pay for sanitary napkins. METHODS:
      A cross-sectional study was done in villages under the Comprehensive Rural Health
      Services Project (CRHSP), situated in Ballabgarh, Haryana. The study participants
      were women in the age group of 15-45 years. Nine villages were selected randomly
      while the number of respondents in each selected village was decided through the
      probability propor-tionate to size sampling method. The households were selected
      using systematic sampling. One woman was interviewed in each household using a
      pre-tested questionnaire. RESULTS: A total of 995 women were interviewed. A
      majority of them (62%) were unaware of the reason(s) for menstruation. The role
      of the health sector in providing information regarding menstruation was low as
      only a few women (1.5%) had got information from the auxiliary nurse midwife
      (ANM)/health worker (HW). For the majority of women, besides religious
      activities, other routine activities did not suffer during menstruation. Only
      28.8% of women were using sanitary napkins and of those who did not use napkins,
      only one-fourth (25.3%) were willing to buy them. The mean (SD) price per napkin
      that these women were ready to pay was Rs. 0.54 (0.43), equivalent to US$ 0.01.
      CONCLUSION: Women in the reproductive age group should be provided with
      appropriate information about menstruation, and they should be told about the
      advantages of using sanitary napkins. Health sector functionaries should play a
      proactive role in the delivery of such information.

PMID- 25073991
TI  - Juvenile ankylosing spondylitis in Turner syndrome.
AB  - Juvenile ankylosing spondylitis (JAS) is a chronic autoimmune disorder which
      causes considerable morbidity when left untreated; it occurs predominantly in
      men. We describe an Asian Indian woman who had JAS with phenotypic features of
      Turner syndrome (TS) and was found to be a mosaic for 45, X/46, X, psu idic (X)
      (p11) by karyotyping and fluorescence in situ hybridization (FISH) studies of
      peripheral blood. The absence of Y chromosome material was confirmed by FISH.
      Haplo-insufficiency of the X chromosome can predispose to autoimmunity. To the
      best of our knowledge, this is the first report of JAS in association with mosaic
      Turner syndrome. This case highlights the possible effects of gene dosage in
      development of an autoimmune disease. 

PMID- 25073992
TI  - E-cigarettes as tobacco harm-reduction tool: a promise or peril?

PMID- 25073993
TI  - Tuberculosis and diabetes mellitus: time for an integrated approach.

PMID- 25073994
TI  - Accreditation of public health education in India: Enhancing quality, competence
      and trust.
AB  - With an increase in the number of institutes offering public health education,
      there is a need for discussion on future directions and challenges. The World
      Health Report 2006 identified the need to improve the quality of public health
      education. There are various mechanisms and bodies that look after accreditation
      issues in several countries. The Council on Education for Public Health in the
      USA assists in the accreditation of schools of public health, as well as public
      health programmes. The Australian Network of Academic Public Health Institutions
      is actively engaged in discussions to improve the quality of its programme and
      institutions. In Europe, the European Agency for Accreditation in Public Health
      Education is responsible for accreditation. The South-East Asia Public Health
      Education Institutes Network facilitates accreditation of public health education
      in the region. In India, public health education varies across institutes. India
      needs an accreditation system to ensure that public health education is of the
      desired quality. Certain initiatives, such as conferences, consultation and the
      Calcutta Declaration, have been taken in the past two decades. However, the ideas
      mooted have yet to be translated into reality. The broad framework for
      accreditation may entail an institutional self-assessment against set standards,
      preparation of a database, cataloguing, and site visits by a peer team. There is
      a need for an apical body with all stakeholders participating in the process.
      Accreditation has specific benefits, but there are critical challenges as well.
      For example, the autonomy of the institutions needs to be protected, the
      accreditation bodies should exhibit professionalism and substantial financial
      resources are required. Before tackling specific criteria for accreditation, it
      is necessary to define a collective vision for schools of public health in India.

PMID- 25073995
TI  - A man with abdominal pain and melaena.

PMID- 25073996
TI  - Letter from Chennai.

PMID- 25073997
TI  - Letter from Glasgow.

PMID- 25074001
TI  - Accidental Jatropha curcas poisoning in children.

PMID- 25074002
TI  - Preserving the legacy: the history of Indian neurosciences.

PMID- 25074003
TI  - Alopecia areata associated with hypothyroidism.

PMID- 25074004
TI  - Infectious hepatitis in Delhi (1955-56): a critical study-epidemiology. 1957.

PMID- 25074006
TI  - Elucidation of cellular transport mechanisms awarded 2013 Nobel Prize in
      Medicine/Physiology.

PMID- 25074005
TI  - Healthcare politics shuts down US federal government.

PMID- 25074007
TI  - Supreme Court orders highest ever compensation in case of medical negligence.

PMID- 25074008
TI  - Mozart may prevent heart transplant rejection: discovery wins Harvard
      University's Ig Nobel 2013 prize in medicine.

PMID- 25074009
TI  - Cell phones may not be unsafe, rules WHO.

PMID- 25074011
TI  - Ombitasvir: a potent pan-genotypic inhibitor of NS5A for the treatment of
      hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) chronically infects about 150,000,000 people worldwide
      and is a relevant cause of liver cirrhosis, hepatocellular carcinoma and death.
      Antiviral treatment is rapidly moving from interferon (IFN)-based therapy to IFN
      free approaches. This review focuses on the mechanism of action,
      pharmacokinetics, efficacy, tolerability, safety and resistance of ombitasvir,
      which is an inhibitor of the HCV nonstructural protein 5A. The pharmacokinetics
      of ombitasvir enables its once daily administration. In vivo, in combinations
      with other oral direct acting antivirals, ombitasvir achieves very high rates of
      sustained virological response (about 95%) in patients with HCV genotype 1
      infection with a good tolerability. Resistance profiling revealed a low barrier
      to resistance when given as monotherapy. However, coadministration of ombitasvir
      and other antivirals enhances its barrier to resistance. In conclusion,
      ombitasvir is a good drug to be used in IFN-free combinations for the treatment
      of chronic hepatitis C. 

PMID- 25074013
TI  - Similar postoperative safety between primary and revisional gastric bypass for
      failed gastric banding.
AB  - IMPORTANCE: Adjustable gastric bands are widely used because of low postoperative
      morbidity, but their long-term results are poor, often leading to revisional
      surgery. OBJECTIVE: To assess the safety of revisional procedures by comparing
      the 30-day outcomes of primary gastric bypass vs revisions following failed
      adjustable gastric banding. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      review using logistic regression models to compute odds ratios (95% CIs) across
      preoperative body mass index (calculated as weight in kilograms divided by height
      in meters squared) quartiles to evaluate the risk for major adverse outcomes at
      30 days (death, venous thromboembolism, reinterventions, and failure to be
      discharged). The prospective database of a single university surgical center in
      Paris, France, was queried for clinical and other relevant data among all
      patients undergoing primary or revisional laparoscopic gastric bypass between
      January 1, 2004, and June 30, 2013. MAIN OUTCOMES AND MEASURES: The primary
      outcome was a comparison between 30-day outcomes of primary gastric bypass and
      procedures following failed adjustable gastric banding. RESULTS: In total, 831
      patients had a primary procedure (group 1), and 177 patients had a secondary
      procedure after failed adjustable gastric banding (group 2). Overall, 78.7% of
      patients were female, the mean (SD) patient age was 42.6 (11.6) years, the mean
      (SD) body mass index was 47.6 (7.6), and mortality at 30 days was 0.5%. The rates
      of major adverse outcomes were similar in group 1 (7.8%) and group 2 (8.5%) (P =
      .77). In multivariate analyses, odds ratios for major adverse outcomes across
      preoperative body mass index quartiles (<42, 42-46, >46 to 52, and >52) were
      1.00, 0.39 (95% CI, 0.20-0.77; P = .006), 0.55 (95% CI, 0.30-1.02; P = .06), and
      0.50 (95% CI, 0.27-0.94; P = .03), respectively. CONCLUSIONS AND RELEVANCE: The
      30-day major adverse outcome rates were similar for primary gastric bypass and
      for procedures following failed adjustable gastric banding. Long-term comparative
      studies are required to better understand the quadratic relationship between body
      mass index and early postoperative outcomes.

PMID- 25074012
TI  - Signatures of selection in sheep bred for resistance or susceptibility to
      gastrointestinal nematodes.
AB  - BACKGROUND: Gastrointestinal nematodes are one of the most serious causes of
      disease in domestic ruminants worldwide. There is considerable variation in
      resistance to gastrointestinal nematodes within and between sheep breeds, which
      appears to be due to underlying genetic diversity. Through selection of resistant
      animals, rapid genetic progress has been demonstrated in both research and
      commercial flocks. Recent advances in genome sequencing and genomic technologies
      provide new opportunities to understand the ovine host response to
      gastrointestinal nematodes at the molecular level, and to identify polymorphisms
      conferring nematode resistance. RESULTS: Divergent lines of Romney and Perendale
      sheep, selectively bred for high and low faecal nematode egg count, were
      genotyped using the Illumina(r) Ovine SNP50 BeadChip. The resulting genome-wide
      SNP data were analysed for selective sweeps on loci associated with resistance or
      susceptibility to gastrointestinal nematode infection. Population differentiation
      using FST and Peddrift revealed sixteen regions, which included candidate genes
      involved in chitinase activity and the cytokine response. Two of the sixteen
      regions identified were contained within previously identified QTLs associated
      with nematode resistance. CONCLUSIONS: In this study we identified fourteen novel
      regions associated with resistance or susceptibility to gastrointestinal
      nematodes. Results from this study support the hypothesis that host resistance to
      internal nematode parasites is likely to be controlled by a number of loci of
      moderate to small effects.

PMID- 25074014
TI  - Determination of tyrosinase substrate-binding modes reveals mechanistic
      differences between type-3 copper proteins.
AB  - Tyrosinase is responsible for the two initial enzymatic steps in the conversion
      of tyrosine to melanin. Many tyrosinase mutations are the leading cause of
      albinism in humans, and it is a prominent biotechnology and pharmaceutical
      industry target. Here we present crystal structures that show that both
      monophenol hydroxylation and diphenol oxidation occur at the same site. It is
      suggested that concurrent presence of a phenylalanine above the active site and a
      restricting thioether bond on the histidine coordinating CuA prevent
      hydroxylation of monophenols by catechol oxidases. Furthermore, a conserved water
      molecule activated by E195 and N205 is proposed to mediate deprotonation of the
      monophenol at the active site. Overall, the structures reveal precise steps in
      the enzymatic catalytic cycle as well as differences between tyrosinases and
      other type-3 copper enzymes. 

PMID- 25074015
TI  - A retrospective review of enteral nutrition support practices at a tertiary
      pediatric hospital: A comparison of prolonged nasogastric and gastrostomy tube
      feeding.
AB  - BACKGROUND & AIMS: Despite the frequent use of tube-mediated enteral feeding,
      there is little evidence clarifying best practices pertaining to prolonged
      nasogastric and gastrostomy tube use in children. At the Montreal Children's
      Hospital, tube feeding practices are non-standardized and highly variable, with
      many patients remaining on protracted nasogastric feeds. We aimed to characterize
      enteral nutrition practices at our institution and to compare prolonged
      nasogastric and gastrostomy tube use, hypothesizing that earlier gastrostomy
      improves outcomes, particularly the development of food refusal. METHODS: In this
      retrospective cohort study, we reviewed the charts of children beginning long
      term (>3 months) nasogastric or gastrostomy feeds at our institution between
      January 2007 and December 2011, with follow-up until May 2013. Patient
      demographics, anthropometric parameters, swallowing assessment, tube feeding
      duration and complications were recorded. RESULTS: Among 166 patients, the median
      total tube feeding duration was 24.9 (3.0-75.6) months and varied with underlying
      disease and swallowing assessment. The median duration of nasogastric tube use
      was 7.8 (0.7-45.3) months. Food refusal was significantly associated with
      nasogastric tube exposure >3 months (RR 3.3, p < 0.001, NNT = 3) and
      anthropometric outcomes were superior in gastrostomy-fed patients. Rates of
      aspiration pneumonia were similar in both groups. Despite more initial opposition
      to gastrostomy and a higher complication rate, gastrostomy users appeared more
      satisfied with their experience, as demonstrated by a much lower discontinuation
      rate than observed in the nasogastric group. CONCLUSIONS: Prolonged nasogastric
      feeding is common at our institution. Its association with increased food refusal
      and less favorable anthropometric outcomes may warrant earlier gastrostomy
      placement.

PMID- 25074017
TI  - Red clover extract for alleviating hot flushes in postmenopausal women: a meta
      analysis.
AB  - The safety and efficacy of red clover for alleviating menopausal hot flushes are
      yet to be established. The aim of this meta-analysis was to generate evidence
      from published literature regarding red clover as a treatment option for
      menopausal hot flushes. The results showed that red clover when compared to
      placebo was effective in reducing menopausal hot flushes when administered for 3
      4 months (MD=-1.34, 95% CI=-1.90 to -0.77, p<0.00001), but their effect did not
      persist at 12 months (MD=0.89, 95% CI=-0.07 to 1.85, p=0.07). 

PMID- 25074019
TI  - Biology-oriented synthesis: harnessing the power of evolution.
AB  - For scientists to gain a better understanding of nature, biological research is
      greatly aided by small-molecule modulators that perturb protein activity without
      fundamentally altering the underlying biological systems. The number of possible
      interfering molecules, however, is so vast that, due to limitations in existing
      matter and time required for synthesis, they cannot be covered comprehensively.
      Because proteins and their cognate natural product ligands and substrates co
      evolved, these naturally occurring ligands can serve as structural starting
      points to explore the biologically relevant chemical space. To this end, known
      natural products are structurally classified on the basis of their core scaffolds
      and hierarchically arranged in the "natural product tree", which can be annotated
      for bioactivity and intuitively navigated with currently available software.
      Biologically relevant scaffolds inspire the synthesis of compound libraries
      enriched in biological activity. This Perspective describes the development of
      "biology-oriented synthesis" as a guiding principle to harness the power of
      evolution in the quest for novel bioactive small molecules for chemical biology
      research and drug discovery. 

PMID- 25074016
TI  - Back to basics: a bilingual advantage in infant visual habituation.
AB  - Comparisons of cognitive processing in monolinguals and bilinguals have revealed
      a bilingual advantage in inhibitory control. Recent studies have demonstrated
      advantages associated with exposure to two languages in infancy. However, the
      domain specificity and scope of the infant bilingual advantage in infancy remains
      unclear. In the present study, 114 monolingual and bilingual infants were
      compared in a very basic task of information processing-visual habituation-at 6
      months of age. Bilingual infants demonstrated greater efficiency in stimulus
      encoding as well as in improved recognition memory for familiar stimuli as
      compared to monolinguals. Findings reveal a generalized cognitive advantage in
      bilingual infants that is broad in scope, early to emerge, and not specific to
      language.

PMID- 25074018
TI  - Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional
      mechanisms.
AB  - Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation
      induced proliferation and cytokine expression. The molecular mechanisms
      responsible for the inactivation of effector T cells by Tregs remain yet to be
      fully characterized. We report that T-helper cells stimulated in the presence of
      Tregs quickly activate NFAT1 and have increased NFAT1-dependent expression of the
      transcription repressor Ikaros. NFAT1 deficiency or dominant-negative Ikaros
      compromises Treg-mediated inhibition of T-helper cells in vitro and in vivo.
      Thus, our results place NFAT-dependent mechanisms as general regulators of T-cell
      tolerance and show that Treg-mediated suppression of T-helper cells results from
      the activation of NFAT-regulated gene expression. 

PMID- 25074020
TI  - Foundational issues in risk analysis.

PMID- 25074021
TI  - The incidence of thyroid carcinoma in the nodules. A retrospective study.
AB  - Fine-needle aspiration (22G) is the diagnostic procedure chosen to study the
      nature of suspicious thyroid nodules. In 2008 the SIAPEC-IAP work group issued
      the results of Italian Consensus about the clinical management of patients with
      thyroid nodular disease, and introduced diagnostic categories aimed to
      standardize the diagnostic and therapeutic process of patients affected by
      thyroid nodules. This retrospective study is aimed to assess the incidence of
      carcinoma at definitive histological examination after total thyroidectomy of
      nodules with TIR3 cytological diagnosis. KEY WORDS: CEUS, FNAC, Surgery, Thyroid
      nodules.

PMID- 25074023
TI  - Relationship between the complement system, risk factors and prediction models in
      age-related macular degeneration.
AB  - Studies performed over the past decade in humans and experimental animals have
      been a major source of information and improved our understanding of how
      dysregulation of the complement system contributes to age-related macular
      degeneration (AMD) pathology. Drusen, the hall-mark of dry-type AMD are reported
      to be the by-product of complement mediated inflammatory processes. In wet AMD,
      unregulated complement activation results in increased production of angiogenic
      growth factors leading to choroidal neovascularization both in humans and in
      animal models. In this review article we have linked the complement system with
      modifiable and non-modifiable AMD risk factors as well as with prediction models
      of AMD. Understanding the association between the complement system, risk factors
      and prediction models will help improve our understanding of AMD pathology and
      management of this disease. 

PMID- 25074022
TI  - Quantitative trait loci and candidate genes underlying genotype by environment
      interaction in the response of Arabidopsis thaliana to drought.
AB  - Drought stress was imposed on two sets of Arabidopsis thaliana genotypes grown in
      sand under short-day conditions and analysed for several shoot and root growth
      traits. The response to drought was assessed for quantitative trait locus (QTL)
      mapping in a genetically diverse set of Arabidopsis accessions using genome-wide
      association (GWA) mapping, and conventional linkage analysis of a recombinant
      inbred line (RIL) population. Results showed significant genotype by environment
      interaction (G*E) for all traits in response to different watering regimes. For
      the RIL population, the observed G*E was reflected in 17 QTL by environment
      interactions (Q*E), while 17 additional QTLs were mapped not showing Q*E. GWA
      mapping identified 58 single nucleotide polymorphism (SNPs) associated with loci
      displaying Q*E and an additional 16 SNPs associated with loci not showing Q*E.
      Many candidate genes potentially underlying these loci were suggested. The genes
      for RPS3C and YLS7 were found to contain conserved amino acid differences when
      comparing Arabidopsis accessions with strongly contrasting drought response
      phenotypes, further supporting their candidacy. One of these candidate genes co
      located with a QTL mapped in the RIL population. 

PMID- 25074024
TI  - Utility of prechemotherapy evaluation of left ventricular function for patients
      with lymphoma.
AB  - BACKGROUND: Published guidelines recommend baseline cardiac function testing
      before initiating anthracycline-based chemotherapy. These recommendations are
      based largely on consensus, and there is little information regarding how often
      testing leads to alterations in therapy or whether testing is able to predict
      subsequent cardiac toxicity. PATIENTS AND METHODS: We performed a retrospective
      analysis of patients with Hodgkin lymphoma and non-Hodgkin lymphoma to determine
      whether there was a prechemotherapy evaluation of left ventricular function and
      whether findings from the evaluation led to alterations in therapy. Records also
      were reviewed to evaluate subsequent test results of cardiac function. RESULTS:
      We identified 309 patients with lymphoma between 2004 and 2012 with a planned
      anthracycline- or anthracenedione-based regimen. Of this total, 232 patients
      (75%) had a pretreatment cardiac evaluation. There were 201 patients (87%) in
      this group with no history of cardiac disease. Although 22 of these patients
      (11%) had abnormal echocardiograms, none had a change in therapy and no
      subsequent cases of cardiomyopathy were identified. Five of the remaining 179
      patients with a normal cardiac evaluation developed a cardiomyopathy. Thirty-one
      patients had a history of cardiac disease, and only 4 patients had a change in
      therapy. There were 77 patients (25%) who did not have a prechemotherapy cardiac
      evaluation. No subsequent cases of cardiomyopathy were identified in this group.
      CONCLUSIONS: Pretreatment evaluation rarely leads to a change in management and
      is not helpful in predicting subsequent cardiomyopathy. Guidelines that recommend
      evaluation of left ventricular function in all patients before anthracycline
      based chemotherapy should be reexamined.

PMID- 25074025
TI  - Patients' experiences of the management of lower back pain in general practice:
      use of diagnostic imaging, medication and provision of self-management advice.
AB  - Lower back pain is prevalent in the general community. Guidelines recommend
      against the use of diagnostic imaging unless 'red flags' are present that may
      indicate a potentially serious cause. This paper reports on a cross-sectional
      electronic survey to investigate self-reported experiences of lower back pain
      management among Australian general practice patients. Of the 872 participants,
      551 (63%) reported that they had experienced lower back pain in the past 12
      months. Approximately 40% of patients who had experienced lower back pain
      reported that they had consulted their general practitioner (GP) regarding this
      issue. Among those who sought general practice care, 67% reported being referred
      for diagnostic imaging. Those who received imaging were more likely to have been
      prescribed medication by their GP, but received self-management advice at the
      same rate as those who had not been referred. Rates of self-reported referral for
      diagnostic imaging were higher than expected, given the low prevalence of
      potentially serious causes for lower back pain reported in the international
      literature. However, it remains unclear whether this is due to poor guideline
      adherence by GPs or lack of specificity in the red flags identified in
      guidelines. Findings suggest the need for improvements in the provision of
      evidence-based self-management advice.

PMID- 25074027
TI  - Cultural variations in shame's responses: a dynamic perspective.
AB  - The diverse literature on shame has led to disparate and often contradictory
      conclusions regarding the emotion's nature and consequences. The article proposes
      a motivational theory of shame that accounts for these discrepant findings. The
      first part of the article uses the concept of active avoidance to outline a
      dynamic motivational perspective in which shame is based initially in behavioral
      inhibition that then incorporates subsequent behavioral activation. The
      motivational shift is guided by shame's relational phenomenology and the
      normative beliefs associated with shame. In the second part, the motivational
      perspective is used to account for variations in shame's consequences.
      Externalizing and restorative tendencies of shame are culturally variable and due
      to differences in behavioral activation associated with the emotion. However,
      withdrawal tendencies occur across cultural contexts because of shame's basis in
      inhibition. Issues in conducting cross-cultural studies on emotion and
      suggestions for future research are discussed. 

PMID- 25074028
TI  - Evolution of NO2 levels in Spain from 1996 to 2012.
AB  - We report on the evolution of tropospheric nitrogen dioxide (NO2) over Spain,
      focusing on the densely populated cities of Barcelona, Bilbao, Madrid, Sevilla
      and Valencia, during 17 years, from 1996 to 2012. This data series combines
      observations from in-situ air quality monitoring networks and the satellite-based
      instruments GOME and SCIAMACHY. The results in these five cities show a smooth
      decrease in the NO2 concentrations of ~2% per year in the period 1996-2008, due
      to the implementation of emissions control environmental legislation, and a more
      abrupt descend of ~7% per year from 2008 to 2012 as a consequence of the economic
      recession. In the whole Spanish territory the NO2 levels have decreased by ~22%
      from 1996 to 2012. Statistical analysis of several economic indicators is used to
      investigate the different factors driving the NO2 concentration trends over Spain
      during the last two decades. 

PMID- 25074026
TI  - Perceived exertion at work in women with fibromyalgia: explanatory factors and
      comparison with healthy women.
AB  - OBJECTIVE: To investigate perceived exertion at work in women with fibromyalgia.
      DESIGN: A controlled cross-sectional multi-centre study. SUBJECTS AND METHODS:
      Seventy-three women with fibromyalgia and 73 healthy women matched by occupation
      and physical workload were compared in terms of perceived exertion at work (0
      14), muscle strength, 6-min walk test, symptoms rated by Fibromyalgia Impact
      Questionnaire (FIQ), work status (25-100%), fear avoidance work beliefs (0-42),
      physical activity at work (7-21) and physical workload (1-5). Spearman's
      correlation coefficient and linear regression analysis were conducted. RESULTS:
      Perceived exertion at work was significantly higher in the fibromyalgia group
      than in the reference group (p = 0.002), while physical activity at work did not
      differ between the groups. Physical capacity was lower and symptom severity
      higher in fibromyalgia compared with references (p < 0.05). In fibromyalgia,
      perceived exertion at work showed moderate correlation with physical activity at
      work, physical workload and fear avoidance work beliefs (rs = 0.53-0.65, p <
      0.001) and a fair correlation with anxiety (rs = 0.26, p = 0.027). Regression
      analysis indicated that the physical activity at work and fear avoidance work
      beliefs explained 50% of the perceived exertion at work. CONCLUSION: Women with
      fibromyalgia perceive an elevated exertion at work, which is associated with
      physical work-related factors and factors related to fear and anxiety.

PMID- 25074029
TI  - Monitoring disease activity and progression in Crohn's disease. A Swiss
      perspective on the IBD ahead 'optimised monitoring' recommendations.
AB  - BACKGROUND AND AIMS: The structured IBD Ahead 'Optimised Monitoring' programme
      was designed to obtain the opinion, insight and advice of gastroenterologists on
      optimising the monitoring of Crohn's disease activity in four settings: (1)
      assessment at diagnosis, (2) monitoring in symptomatic patients, (3) monitoring
      in asymptomatic patients, and (4) the postoperative follow-up. For each of these
      settings, four monitoring methods were discussed: (a) symptom assessment, (b)
      endoscopy, (c) laboratory markers, and (d) imaging. Based on literature search
      and expert opinion compiled during an international consensus meeting,
      recommendations were given to answer the question 'which diagnostic method, when,
      and how often'. The International IBD Ahead Expert Panel advised to tailor this
      guidance to the healthcare system and the special prerequisites of each country.
      The IBD Ahead Swiss National Steering Committee proposes best-practice
      recommendations adapted for Switzerland. METHODS: The IBD Ahead Steering
      Committee identified key questions and provided the Swiss Expert Panel with a
      structured literature research. The expert panel agreed on a set of statements.
      During an international expert meeting the consolidated outcome of the national
      meetings was merged into final statements agreed by the participating
      International and National Steering Committee members - the IBD Ahead 'Optimized
      Monitoring' Consensus. RESULTS: A systematic assessment of symptoms, endoscopy
      findings, and laboratory markers with special emphasis on faecal calprotectin is
      deemed necessary even in symptom-free patients. The choice of recommended imaging
      methods is adapted to the specific situation in Switzerland and highlights the
      importance of ultrasonography and magnetic resonance imaging besides endoscopy.
      CONCLUSION: The recommendations stress the importance of monitoring disease
      activity on a regular basis and by objective parameters, such as faecal
      calprotectin and endoscopy with detailed documentation of findings. Physicians
      should not rely on symptoms only and adapt the monitoring schedule and choice of
      options to individual situations.

PMID- 25074030
TI  - Length-scale dependent transport properties of colloidal and protein solutions
      for prediction of crystal nucleation rates.
AB  - We propose a scaling equation describing transport properties (diffusion and
      viscosity) in the solutions of colloidal particles. We apply the equation to 23
      different systems including colloids and proteins differing in size (range of
      diameters: 4 nm to 1 MUm), and volume fractions (10(-3)-0.56). In solutions under
      study colloids/proteins interact via steric, hydrodynamic, van der Waals and/or
      electrostatic interactions. We implement contribution of those interactions into
      the scaling law. Finally we use our scaling law together with the literature
      values of the barrier for nucleation to predict crystal nucleation rates of hard
      sphere like colloids. The resulting crystal nucleation rates agree with existing
      experimental data. 

PMID- 25074031
TI  - Treatment of osteonecrosis in systemic lupus erythematosus: a review.
AB  - Osteonecrosis (ON) is a devastating illness that can lead to severe joint disease
      in young patients. The pathogenesis of ON is largely unknown; however, there have
      been numerous reports associating risk factors including systemic lupus
      erythematosus (SLE) with the disease. The risk of ON for SLE patients is believed
      to be a result of both the SLE disease state itself and the concomitant use of
      corticosteroids. The objective of osteonecrosis treatment is typically to halt
      progression or delay the onset of end-stage arthritis that may require a total
      joint arthroplasty (TJA). Joint-preserving procedures are attempted for pre
      collapse and some post-collapse lesions. After severe subchondral collapse has
      occurred, TJA is often necessary to relieve pain. The purpose of this article is
      to draw attention to recent evidence regarding several treatment options for the
      management of SLE-associated ON, including lesion observation, medication, joint
      preserving techniques, and TJA. 

PMID- 25074033
TI  - Copper-mediated C-H(sp2)/C-H(sp3) coupling of benzoic acid derivatives with ethyl
      cyanoacetate: an expedient route to an isoquinolinone scaffold.
AB  - A facile, copper-mediated, direct C-H(sp(2))/C-H(sp(3)) bond coupling of benzoic
      acid derivatives with ethyl cyanoacetate by the deployment of an 8-aminoquinoline
      moiety as a bidentate directing group is disclosed. Such a unique transformation
      provides a new strategy for the construction of an isoquinolinone scaffold as one
      of the privileged cores. 

PMID- 25074032
TI  - Rituximab and lupus--a promising pair?
AB  - Systemic lupus erythematosus (SLE) is a clinically diverse and potentially life
      threatening auto-immune disease that can affect almost any organ system. Although
      much is still unknown regarding its pathogenesis, B cell abnormalities are
      thought to be central. A high relapse rate along with the toxicity associated
      with conventional treatments signify the need for more tailored approaches in
      this very heterogeneous disease. Both its mechanism targeting B cells and a
      relatively large number of case series and observational studies have suggested
      that the B cell-depleting agent rituximab could be a potent SLE drug. However,
      two randomized controlled trials failed to meet efficacy endpoints. Nevertheless,
      rituximab has continued to be used as an off-label alternative mainly in patients
      refractory to conventional immunosuppressive treatment. This article will review
      the current role of rituximab in SLE. 

PMID- 25074034
TI  - [Clinical usefulness of ultrasound-guided alcohol sclerosis in patients with
      breast fistulas].
AB  - OBJECTIVE: To study the clinical usefulness of ultrasound-guided alcohol
      sclerosis as a treatment alternative to surgical intervention for breast
      fistulas. MATERIAL AND METHODS: This was a retrospective study of data collected
      in a hospital breast unit over a three-year period (January 2011 through December
      2013). The procedure consists of introducing a sclerosing solution into the lumen
      of the breast fistula under ultrasound guidance. All cases were reviewed by a
      multidisciplinary committee; patients were offered ultrasound-guided alcohol
      sclerosis as a first treatment option with surgical intervention as a rescue
      therapy for those with unsatisfactory outcomes. RESULTS: Ten fistulas were
      treated in 9 women (median age, 33 y; interquartile range 18.5 y). Five patients
      (50%) attributed the clinical findings to recurrent mastitis, four (40%) to a
      previous surgical intervention, and one (10%) to lactation. Seven patients (78%)
      were smokers. The procedure was well tolerated: nine patients (90%) rated the
      pain as one or 2 (mild pain) on a visual analogue scale. There were no immediate
      complications. The response to treatment was considered excellent (absence of
      secretion and complete closure) in eight fistulas (80%). CONCLUSION: Ultrasound
      guided alcohol sclerosis achieved excellent outcomes in 80% of cases and is a
      viable alternative to surgical treatment.

PMID- 25074035
TI  - Knowledge and skill in motion: layers of Tibetan medical education in India.
AB  - This article examines the transmission of Tibetan medical knowledge in the
      Himalayan region of Ladakh (India), taking three educational settings as
      ethnographic ports of entry. Each of these corresponds to a different operating
      mode in the standardisation of medical knowledge and learning processes, holding
      profound implications for the way this therapeutic tradition is known, valued,
      applied and passed on to the next generation. Being at the same time a cause and
      a consequence of intra-regional variability in Tibetan medicine, the three
      institutional forms coexist in constant interaction with one another. The authors
      render this visible by examining the 'taskscapes' that characterize each learning
      context, that is to say, the specific and interlocking sets of practices and
      tasks in which a practitioner must be skilled in order to be considered
      competent. The authors build upon this notion by studying two fields of
      transmission and practice, relating to medicine production and medical ethics.
      These domains of enquiry provide a rich grounding from which to examine the
      transition from enskilment to education, as well as the overlaps between them,
      and to map out the connections linking different educational forms to social and
      medical legitimacy in contemporary India. 

PMID- 25074036
TI  - Phase I study of adjuvant gemcitabine or S-1 in patients with biliary tract
      cancers undergoing major hepatectomy: KHBO1003 study.
AB  - BACKGROUND: Standardized adjuvant therapy is not performed after major
      hepatectomy for biliary tract cancer (BTC) because of frequent adverse events,
      which may be caused by insufficient liver function. Therefore, the aim of this
      multicenter study (KHBO1003) was to determine the safety protocol for adjuvant
      chemotherapy after major hepatectomy. METHODS: Within 12 weeks of R0 or R1 major
      hepatectomy (hemihepatectomy or trisectionectomy) for BTC, the following adjuvant
      chemotherapy was performed for 6 months: 800-1,000 mg/m(2) gemcitabine on days 1,
      8, and 15 and then every 3-4 weeks or 40-80 mg/m(2)/day S-1 on days 1-28 and
      every 3-6 weeks. Major dose-limited toxicity (DLT) was defined as grade 4
      hematotoxicity, grade 3/4 febrile neutropenia, grade 3/4 non-hematotoxicity,
      skipped gemcitabine on days 8 and 15, or halting the course at or after 14 days.
      Dose-escalation and de-escalation decisions were based on the continual
      reassessment method. Every three patients were alternately assigned to each arm.
      RESULTS: Thirty-three patients (14 intrahepatic bile duct, 1 gall bladder, 18
      extrahepatic bile duct) were enrolled in this study from February 2011 to July
      2012 (n = 18 gemcitabine, n = 15 S-1). At 10% of DLT, the recommended dose was
      1,000 mg/m(2) gemcitabine biweekly and 80 mg/m(2)/day S-1 on days 1-28 and every
      6 weeks. Major DLT and adverse drug reactions were neutropenia. No grade 3 or 4
      non-hematological adverse events were noted. CONCLUSION: We determined RDs for
      gemcitabine and S-1 adjuvant chemotherapy after major hepatectomy with a DLT that
      does not exceed 10%.

PMID- 25074037
TI  - Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4
      diol on Abeta-stressed PC12 cells.
AB  - Amyloid beta-protein (Abeta) is involved in the pathogenesis of Alzheimer's
      disease (AD). Abeta induces free radical production in neuronal cells, leading to
      oxidative stress and up-regulation of c-Jun N-terminal kinases (JNK),
      extracellular-signal-regulated kinases (ERK), p38 mitogen-activated protein
      kinase (MAPK) pathways and pro-apoptotic Bax expression. Sesamin has been shown
      to have protection to several models of neurodegenerative diseases by its
      antioxidant and anti-inflammatory properties. In the present study, we examined
      the neuroprotective effect of a sesamin derivative, 3-bis (3-methoxybenzyl)
      butane-1,4-diol (BBD) on Abeta1-42 induced cytotoxicity of PC12 cells. Abeta1-42
      induced lipid peroxidation, calcium, reactive oxygen species from the PC12 cells.
      The effect of BBD on these harmful factors and the related signaling pathways
      were examined by biochemical and western blot assays. The result showed that BBD
      protected PC12 cells from Abeta1-42 induced cytotoxicity with the increased cell
      viability and acetylcholine release, and the decreased lactate dehydrogenase,
      malondialdehyde and calcium release. BBD significantly reduced Abeta-induced JNK,
      ERK, p38 MAPK pathways and Bax expression in PC12 cells. Therefore the
      neuroprotective effect of BBD on Abeta-induced cytotoxicity was involved with
      antioxidant and anti-inflammatory effects. The result would help the development
      of new CNS drug for protection of AD. 

PMID- 25074038
TI  - Hepatoprotective effects of loach (Misgurnus anguillicaudatus) lyophilized powder
      on dimethylnitrosamine-induced liver fibrosis in rats.
AB  - This study investigates the hepatoprotective effects and the potential
      therapeutic mechanisms of loach (Misgurnus anguillicaudatus) lyophilized powder
      (MLP) on dimethylnitrosamine (DMN) induced liver fibrosis in rats. After
      treatment with MLP (50, 100, 200 mg/kg), alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), albumin (Alb), total protein (TP) and
      hydroxyproline (Hyp) levels were detected, to assess the destruction of
      hepatocytes and the extent of liver fibrosis. Matrix metalloproteinase-2 (MMP-2),
      matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), Laminin (LN),
      procollagen type-III (PC-III), collagen type-IV (C-IV), and transforming growth
      factor-beta1 (TGF-beta1) contents in serum were all tested using ELISA kits.
      Alpha-smooth muscle actin (alpha-SMA) and the tissue inhibitor of
      metalloproteinase-1 (TIMP-1) protein contents and distribution were evaluated
      using western blot and immunohistochemical analysis. MLP significantly decreased
      the serum concentrations of ALT, AST, Hyp, HA, LN, PC-III, C-IV, MMP-2, TIMP-1,
      alpha-SMA and TGF-beta1, while increasing the contents of Alb and MMP-9. No
      significant changes on TP serum concentrations were observed. These results
      suggest that MLP has anti-hepatic fibrosis effects and its mechanism may be
      associated with the attenuation of extracellular matrix (ECM) synthesis, the
      acceleration of ECM degradation, inhibition of hepatic stellate cells (HSCs)
      activation and TGF-beta1 expression.

PMID- 25074039
TI  - Validation of cyclooxygenase-2 as a direct anti-inflammatory target of 4-O
      methylhonokiol in zymosan-induced animal models.
AB  - 4-O-methylhonokiol (MH) is known to inhibit inflammation by partially understood
      mechanisms. Here, the anti-inflammatory mechanisms of MH were examined using
      enzymatic, cellular, and animal assays. In enzymatic assays, MH inhibited COX-2
      activity with an IC50 of 0.062 MUM, and also COX-1 with an IC50 of 2.4 MUM. In
      cellular assays, MH was immunotoxic above 10 MUM. At non-toxic concentrations
      (below 3 MUM), MH strongly inhibited COX-2-mediated prostaglandin production with
      an IC50 of 0.1 MUM, whereas did not or slightly affect other functions of B
      cells, T cells, dendritic cells, and macrophages. In an animal model, MH
      inhibited the increase in footpad thickness and popliteal lymph node weight in
      zymosan-injected mice. When analyzed the draining pLNs of zymosan-injected mice
      on day 5, MH inhibited the overall inflammatory responses. However, MH inhibited
      cyclooxygenase (COX)-2-mediated prostaglandin production without affecting tumor
      necrosis factor-alpha production in inflamed tissues within 6 h after zymosan
      injection. In summary, our data suggest that COX-2 may be a direct anti
      inflammatory target of MH in vitro and in vivo. 

PMID- 25074040
TI  - Full-field electroretinogram response to increment and decrement stimuli.
AB  - PURPOSE: The d-wave is typically elicited after the termination of an increment
      flash, but a decrement flash provides an alternative, and perhaps more
      appropriate, stimulus to elicit the d-wave. Here, we investigated the affects of
      stimulus polarity on the electroretinogram (ERG) response. METHODS: ERG responses
      elicited to increment and decrement flashes of varying intensity and duration
      from different background levels were measured from human participants to assess
      the b-wave and d-wave responses as a function of adaptation level and flash
      polarity. Response amplitudes were measured using standard metrics for waveform
      analysis. RESULTS: The amplitude of the b-wave is larger than the d-wave
      regardless of flash polarity when using different background levels which
      maximized the dynamic range of the two waveforms. However, when response
      amplitudes are measured from a common background, the d-wave elicited with
      decrement flash was larger than the b-wave elicited by an increment flash. This
      trend was evident across a range of background levels. The b-wave and d-wave
      become separate entities when flash duration reaches approximately 50 ms. Rapid
      on and rapid-off sawtooth stimuli were also tested against increment and
      decrement step stimuli that were matched in mean luminance. These two stimulus
      types produced different amplitude b-wave and d-wave responses, suggesting
      asymmetric effects of the two stimulus types on the retinal response.
      CONCLUSIONS: We conclude that the response properties of the b-wave and d-wave
      are influenced by the duration, polarity and waveform of the stimulus, as well as
      the background from which the stimuli arise.

PMID- 25074041
TI  - Correlation between early retinal nerve fiber layer loss and visual field loss
      determined by three different perimetric strategies: white-on-white, frequency
      doubling, or flicker-defined form perimetry.
AB  - PURPOSE: To compare the significance of white-on-white standard automated
      perimetry (SAP), matrix frequency doubling technology (FDT), and flicker-defined
      form perimetry (FDF) for early detection of nerve fiber layer loss in early
      glaucoma patients. METHODS: Fifty-one healthy controls and 40 patients with early
      glaucomatous nerve fiber loss were enrolled in this study. Patients had retinal
      nerve fiber layer (RNFL) imaging and visual field testing by SAP, FDT matrix, and
      FDF perimetry at the same visit. Visual field defects were confirmed with two or
      more consecutive examinations by the same types of perimetry. Significant retinal
      nerve fiber layer loss and thus early glaucoma was defined with the reference to
      the RNFL thickness deviation map. The sensitivity, specificity, correlation, MD
      (mean deviation) and PSD (pattern standard deviation) visual field indexes, and
      area under the receiver operating characteristic curve (AUC) of MD and PSD of the
      perimetries were compared. RESULTS: There was a significant difference in nerve
      fiber layer thickness between healthy patients (97.7 +/- 1.34 MUm and patients
      with early glaucoma (84.1 +/- 1.58 MUm) (p < 0.001). Taking all patients with
      early glaucoma into consideration, the sensitivity was highest for FDF perimetry
      (87 %), followed by FDT matrix (62.5 %), and then SAP (40 %). The specificity was
      69.2 % for SAP, 62.8 % for FDT matrix, and 38.4 % for FDF perimetry. MD (mean
      deviation) and PSD (pattern standard deviation) in FDF and FDT matrix were
      significantly different between patients with RNFL loss and those without (p <
      0.05), while no difference could be found in SAP. The AUCs of MD followed a
      similar pattern, with FDF and FDT matrix perimetry having a suitable AUC of >0.6.
      AUCs of PSD were not reliable in all of the three VF devices. CONCLUSIONS: The
      sensitivity for detection of RNFL loss in early glaucoma seems to be higher in
      FDF and FDT matrix than SAP perimetry, while specifity was highest in SAP. Thus,
      simultaneous performance of FDF/FDT matrix and SAP perimetry seems beneficial for
      the correct diagnosis of early glaucoma in patients.

PMID- 25074042
TI  - Modeling the relative influence of fixation and sampling errors on retest
      variability in perimetry.
AB  - BACKGROUND: Our previous studies have shown that in standard automated perimetry
      (SAP) undersampling occurs if sensitivity varies across a visual field faster
      than the Nyquist rate (Nq) for the standard sampling interval of 6 degrees . This
      undersampling was shown to be a major source of test-retest variability. This
      study first tests some of the assumptions of the undersampling idea, and then
      determines the relative contributions to test-retest variability of normal eye
      movements and undersampling. METHODS: In all models fixational jitter was at
      normal levels. The first part investigates the effects of the jitter on the
      Fourier spectra of fields, and stimulus size effects. In the second part fields
      are smoothed in six gradations up to and beyond the point where no undersampling
      could occur. The spatial smoothing gradations covered nil to < Nq/4. For each
      smoothing level the resulting retest variability was determined for each of 11
      bands of scotoma depth (0 to -28.5 dB). RESULTS: As is commonly reported, and as
      undersampling predicts, retest variability was largest for deeper scotoma depths.
      When smoothing suppressed all undersampling effects, the inter-quartile range of
      the residual retest variability averaged only 2.3 +/- 0.33 dB, much smaller than
      for unsmoothed fields (p < 0.003). For the five deepest scotoma depth bands
      (range, -16.5 to -28.5 dB) retest variability was smaller by 6.0 +/- 0.5 dB (p <
      0.0005). CONCLUSIONS: Retest variability appears in large part to be driven by
      undersampling. In real fields, the remaining variance would come from fixation
      errors and physiological sources.

PMID- 25074043
TI  - Eye movements and reading in glaucoma: observations on patients with advanced
      visual field loss.
AB  - PURPOSE: To investigate the relationship between reading speed and eye movements
      in patients with advanced glaucomatous visual field (VF) defects and age-similar
      visually healthy people. METHODS: Eighteen patients with advanced bilateral VF
      defects (mean age: 71, standard deviation [SD]: 7 years) and 39 controls (mean
      age: 67, SD: 8 years) had reading speed measured using short passages of text on
      a computer set-up incorporating eye tracking. Scanpaths were plotted and analysed
      from these experiments to derive measures of 'perceptual span' (total number of
      letters read per number of saccades) and 'text saturation' (the distance between
      the first and last fixation on lines of text). Another eye movement measure,
      termed 'saccadic frequency' (total number of saccades made to read a single
      word), was derived from a separate lexical decision task, where words were
      presented in isolation. RESULTS: Significant linear association was demonstrated
      between perceptual span and reading speed in patients (R (2) = 0.42) and controls
      (R (2) = 0.56). Linear association between saccadic frequency during the LDT and
      reading speed was also found in patients (R (2) = 0.42), but not in controls (R
      (2) = 0.02). Patients also exhibited greater average text saturation than
      controls (P = 0.004). CONCLUSION: Some, but not all, patients with advanced VF
      defects read slower than controls using short text passages. Differences in eye
      movement behaviour may partly account for this variability in patients. These
      patients were shown to saturate lines of text more during reading, which may
      explain previously-reported difficulties with sustained reading.

PMID- 25074044
TI  - Bridging all oral DAA therapy from wait time to post-liver transplant to improve
      HCV eradication?
AB  - BACKGROUND & AIMS: Recurrence of hepatitis C is a major cause of graft loss and
      shortened survival in patients receiving a liver transplant (LT) for end-stage
      hepatitis C virus (HCV) infection. The only way to improve graft and patient
      outcomes is a successful eradication of HCV infection by antiviral therapy either
      before or after transplant. This was achievable in a small proportion of
      recipients by IFN-based regimens, but could be obtained in the majority of them
      by using DAA IFN-free regimens before/after transplant. METHODS: We describe a
      patient with decompensated cirrhosis because of severe recurrent hepatitis C, who
      had a retransplant following treatment with a combination of sofosbuvir and riba
      virin that started during the waiting time and was carried over during both the
      transplant and post-transplant phases for an overall period of 24 weeks. The
      patient gave a written consent to receive Sofosbuvir plus Rbv therapy pre and
      post-transplant. RESULTS: Post-transplant serum HCV-RNA remains undetectable 24
      weeks after discontinuing sofosbuvir and ribavirin (SVR24). CONCLUSIONS: Waiting
      for direct antiviral agents combinations, our findings not only support the use
      of sofosbuvir plus ribavirin as the first-line treatment in all patients on the
      LT waiting list, but also suggest to bridge treatment to the post-transplant
      period in case HCV RNA undetectability for at least 30 days has not been achieved
      at the time of LT.

PMID- 25074045
TI  - Analysis of phosphoproteome in rice pistil.
AB  - As the female reproductive part of a flower, the pistil consists of the ovary,
      style, and stigma, and is a critical organ for the process from pollen
      recognition to fertilization and seed formation. Previous studies on pollen
      pistil interaction mainly focused on gene expression changes with comparative
      transcriptomics or proteomics method. However, studies on protein PTMs are still
      lacking. Here we report a phosphoproteomic study on mature pistil of rice. Using
      IMAC enrichment, hydrophilic interaction chromatography fraction and high
      accuracy MS instrument (TripleTOF 5600), 2347 of high-confidence (Ascore >= 19, p
      <= 0.01), phosphorylation sites corresponding to 1588 phosphoproteins were
      identified. Among them, 1369 phosphorylation sites within 654 phosphoproteins
      were newly identified; 41 serine phosphorylation motifs, which belong to three
      groups: proline-directed, basophilic, and acidic motifs were identified after
      analysis by motif-X. Two hundred and one genes whose phosphopeptides were
      identified here showed tissue-specific expression in pistil based on information
      mining of previous microarray data. All MS data have been deposited in the
      ProteomeXchange with identifier PXD000923
      (http://proteomecentral.proteomexchange.org/dataset/PXD000923). This study will
      help us to understand pistil development and pollination on the posttranslational
      level.

PMID- 25074048
TI  - Taking time seriously: a call to action in mental health research.
AB  - Sociological research on mental health focuses on a multitude of dynamic
      processes, including changes in psychological symptoms or the onset of a mental
      disorder, the course and outcome of mental health problems, and the associations
      of mental health with a wide variety of time-varying social risk and protective
      factors. I argue that scholars studying mental health have, thus far, only
      scratched the surface of the temporal dynamics upon which mental health and
      illness rest. Two broad research issues are reviewed to illustrate important
      temporal issues that have been neglected or understudied in mental health
      research: (1) specific dimensions of temporality, which focus on dynamic
      processes at the individual level, and (2) the age-period-cohort model, which
      focuses on mental health at the population level. Priority topics for future
      research that takes time seriously are recommended. 

PMID- 25074046
TI  - Adalimumab serum levels and antidrug antibodies towards adalimumab in peripheral
      spondyloarthritis: no association with clinical response to treatment or with
      disease relapse upon treatment discontinuation.
AB  - INTRODUCTION: In this study, we evaluated the clinical relevance of serum drug
      levels and antidrug antibodies (ADAbs) with regard to response to treatment, as
      well as to relapse upon treatment discontinuation, in peripheral
      spondyloarthritis (pSpA) patients treated with adalimumab. METHODS: The study
      included 26 pSpA patients treated with adalimumab for either 12 weeks (n = 12) or
      24 weeks (n = 14) in a randomized controlled trial. Patients achieving inactive
      disease measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) at the
      end of the treatment period were classified as responders. Clinical
      characteristics, serum trough adalimumab levels and ADAbs were assessed at the
      end of the treatment period and at follow-up (upon relapse or, in absence of
      relapse, at 16 weeks after discontinuation). RESULTS: Serum adalimumab levels
      measured 2 weeks after the last adalimumab administration ranged from <0.002 to
      23.0 MUg/ml, with a median of 11.5 MUg/ml. These levels were associated with
      neither response to treatment or disease activity measurements at the end of
      treatment nor with the occurrence of relapse and time to relapse after
      discontinuation of treatment. Antiadalimumab ADAbs were present in 23% of the
      patients at end of treatment and in 35% at follow-up after treatment
      discontinuation, indicating that ADAbs were masked by the presence of the drug in
      some patients. However, ADAbs at the end of treatment and at follow-up were not
      different between responders and nonresponders and were not associated with
      relapse upon discontinuation of treatment. CONCLUSIONS: There is no clear
      association between adalimumab serum levels or antiadalimumab ADAbs with clinical
      response to treatment or with relapse upon treatment discontinuation in pSpA.
      TRIAL REGISTRATION: Netherlands Trial Register ID: NTR1806 (registered 7 May
      2009).

PMID- 25074049
TI  - Is isotretinoin treatment safe in patients with known peanut allergy?

PMID- 25074050
TI  - Analytic mind use and interpsychic communication: driving force in analytic
      technique, pathway to unconscious mental life.
AB  - Developed from established psychoanalytic knowledge among different
      psychoanalytic cultures concerning unconscious interpsychic communication,
      analysts' use of their receptive mental experience--their analytic mind use,
      including the somatic, unconscious, and less accessible derivatives--represents a
      significant investigative road to patients' unconscious mental life, particularly
      with poorly symbolized mental states. The author expands upon this tradition,
      exploring what happens when patients unconsciously experience and identify with
      the analyst's psychic functioning. The technical implications of the analyst's
      "instrument" are described, including the analyst's ego regression, creation of
      inner space, taking mind as object, bearing uncertainty and intense affect, and
      self-analysis. Brief case vignettes illustrate the structure and obstacles to
      this work.

PMID- 25074051
TI  - Countertransference identification and fantasy in psychoanalytic process.
AB  - The development of more nuanced understandings of psychoanalytic process is among
      the primary tasks of contemporary psychoanalytic theorizing. One piece of this
      complex undertaking involves the examination of moments when the analyst's
      countertransference position changes. Shifts in the analyst's feelings and
      thoughts in relation to the patient are complex events in which experiences
      registered at many levels of organization and via many modes of perception
      combine to contribute to meaning-making and furthering of the treatment process.
      The author explores the role of fantasy in giving form and meaning to alterations
      experienced as a change of attitude or affect, through close examination of one
      such moment of shift. 

PMID- 25074052
TI  - "These anxieties are not mine": adolescence, the oedipal configuration, and
      transgenerational factors.
AB  - Part 1 of this paper draws on the film Back to the Future (1985) to highlight
      various aspects of adolescence, the oedipal situation, and transgenerational
      factors. The authors then discuss the Oedipus myth and its themes of adolescence,
      narcissism, identity, acting out, repetition, aggression, and the parent-child
      relationship, among others. Comments drawn from Winnicott's writing on oedipal
      issues are discussed as well. As an illustration of some of these issues, in Part
      2, the authors present the clinical case of Osvaldo, age sixteen. Transference
      countertransference issues in this treatment are explored in depth. 

PMID- 25074053
TI  - The blossoms of loss: Ovid's floral metamorphoses and Poussin's realm of flora.
AB  - Alluring and fertile, the flower connotes a locus of desire. The floral
      metamorphic myths narrated in Ovid's Metamorphoses (AD 8a) thematize the price of
      desire--the shame, grief, and rage of rejection and rivalrous defeat--and
      symbolize the generative transformation that frustrated desire and competitive
      loss can promote. In the deceptively beautiful painting Realm of Flora of 1631,
      Nicolas Poussin enlists these myths as allegories of his own great creative leap,
      an aesthetic metamorphosis that followed shattering defeats. Extending the
      association between creativity and object loss to competitive loss, Poussin holds
      a mirror to our powerful drive to prevail and create anew from the ashes of loss.

PMID- 25074054
TI  - Inventing oneself: a note on the effort toward self-cure in a psychotic woman.

PMID- 25074055
TI  - When theory meets practice: the value and limitations of the concept of
      projective identification.

PMID- 25074056
TI  - A passionate psychoanalytic Odyssey.

PMID- 25074064
TI  - Developing a scale to measure stigmatizing attitudes and beliefs about women who
      have abortions: results from Ghana and Zambia.
AB  - The objective of this research was to explore the context of abortion stigma in
      Ghana and Zambia through qualitative research, and develop a quantitative
      instrument to measure stigmatizing attitudes and beliefs about abortion.
      Ultimately, we aimed to develop a scale to measure abortion stigma at the
      individual and community level that can also be used in the evaluation of stigma
      reduction interventions. Focus group discussions were conducted in both countries
      to provide information around attitudes and beliefs about abortion. A 57-item
      instrument was created from these data, pre-tested, and then administered to 531
      individuals (n = 250 in Ghana and n = 281 in Zambia). Exploratory factor analyses
      were conducted on 33 of the original 57 items to identify a statistically and
      conceptually relevant scale. Items with factor loadings > 0.39 were retained. All
      analyses were completed using Stata IC/11.2. Exploratory factor analysis resulted
      in a three-factor solution that explained 53% of the variance in an 18-item
      instrument. The three identified subscales are: (i) negative stereotypes (eight
      items), (ii) discrimination and exclusion (seven items), and (iii) potential
      contagion (three items). Coefficient alphas of 0.85, 0.80, and 0.80 for the three
      subscales, and 0.90 for the full 18-item instrument provide evidence of internal
      consistency reliability. Our Stigmatizing Attitudes, Beliefs, and Actions scale
      captures three important dimensions of abortion stigma: negative stereotypes
      about men and women who are associated with abortion, discrimination/exclusion of
      women who have abortions, and fear of contagion as a result of coming in contact
      with a woman who has had an abortion. The development of this scale provides a
      validated tool for measuring stigmatizing attitudes and beliefs about abortion in
      Ghana and Zambia. Additionally, the scale has the potential to be applicable in
      other country settings. It represents an important contribution to the fields of
      reproductive health, abortion, and stigma.

PMID- 25074065
TI  - Dear Editor.

PMID- 25074067
TI  - Barriers to accessing substance abuse treatment in Mexico: national comparative
      analysis by migration status.
AB  - BACKGROUND: We examined Mexican migrants' perceived barriers to entering
      substance abuse treatment and potential differences by gender. METHODS: This
      study analyzed a subset of household data collected in Mexico in 2011 via the
      Encuesta Nacional de Adicciones (National Survey of Addictions). A sample of
      1,143 individuals who reported using illicit drugs was analyzed using
      multivariate negative binomial models to determine direct and moderated
      relationships of gender, migrant status, and drug dependence with perceived
      barriers to accessing treatment. RESULTS: Significant findings included
      disparities in drug dependence by migrant status. Compared with non-migrant men,
      women who have traveled to the United States was associated with fewer (1.3)
      barriers to access treatment. Fewer barriers to access care were associated with
      individuals residing in other regions of the country, compared to those living in
      Mexico City. CONCLUSIONS: Drug dependence, gender, migration status and regional
      location are factors associated with access to needed treatment. Implications for
      health care policy to develop treatment services infrastructure and for future
      research are discussed in the context of ongoing drug policy reform in Mexico.

PMID- 25074068
TI  - A depth-first search algorithm to compute elementary flux modes by linear
      programming.
AB  - BACKGROUND: The decomposition of complex metabolic networks into elementary flux
      modes (EFMs) provides a useful framework for exploring reaction interactions
      systematically. Generating a complete set of EFMs for large-scale models,
      however, is near impossible. Even for moderately-sized models (<400 reactions),
      existing approaches based on the Double Description method must iterate through a
      large number of combinatorial candidates, thus imposing an immense processor and
      memory demand. RESULTS: Based on an alternative elementarity test, we developed a
      depth-first search algorithm using linear programming (LP) to enumerate EFMs in
      an exhaustive fashion. Constraints can be introduced to directly generate a
      subset of EFMs satisfying the set of constraints. The depth-first search
      algorithm has a constant memory overhead. Using flux constraints, a large LP
      problem can be massively divided and parallelized into independent sub-jobs for
      deployment into computing clusters. Since the sub-jobs do not overlap, the
      approach scales to utilize all available computing nodes with minimal
      coordination overhead or memory limitations. CONCLUSIONS: The speed of the
      algorithm was comparable to efmtool, a mainstream Double Description method, when
      enumerating all EFMs; the attrition power gained from performing flux feasibility
      tests offsets the increased computational demand of running an LP solver. Unlike
      the Double Description method, the algorithm enables accelerated enumeration of
      all EFMs satisfying a set of constraints.

PMID- 25074069
TI  - Comparison of occlusion break responses and vacuum rise times of
      phacoemulsification systems.
AB  - BACKGROUND: Occlusion break surge during phacoemulsification cataract surgery can
      lead to potential surgical complications. The purpose of this study was to
      quantify occlusion break surge and vacuum rise time of current
      phacoemulsification systems used in cataract surgery. METHODS: Occlusion break
      surge at vacuum pressures between 200 and 600 mmHg was assessed with the
      Infiniti(r) Vision System, the WhiteStar Signature(r) Phacoemulsification System,
      and the Centurion(r) Vision System using gravity-fed fluidics. Centurion Active
      FluidicsTM were also tested at multiple intraoperative pressure target settings.
      Vacuum rise time was evaluated for Infiniti, WhiteStar Signature, Centurion, and
      Stellaris(r) Vision Enhancement systems. Rise time to vacuum limits of 400 and
      600 mmHg was assessed at flow rates of 30 and 60 cc/minute. Occlusion break surge
      was analyzed by 2-way analysis of variance. RESULTS: The Centurion system
      exhibited substantially less occlusion break surge than the other systems tested.
      Surge area with Centurion Active Fluidics was similar to gravity fluidics at an
      equivalent bottle height. At all Centurion Active Fluidics intraoperative
      pressure target settings tested, surge was smaller than with Infiniti and
      WhiteStar Signature. Infiniti had the fastest vacuum rise time and Stellaris had
      the slowest. No system tested reached the 600-mmHg vacuum limit. CONCLUSIONS: In
      this laboratory study, Centurion had the least occlusion break surge and similar
      vacuum rise times compared with the other systems tested. Reducing occlusion
      break surge may increase safety of phacoemulsification cataract surgery.

PMID- 25074071
TI  - Glucose control in intensive care: usability, efficacy and safety of Space
      GlucoseControl in two medical European intensive care units.
AB  - BACKGROUND: The Space GlucoseControl system (SGC) is a nurse-driven, computer
      assisted device for glycemic control combining infusion pumps with the enhanced
      Model Predictive Control algorithm (B. Braun, Melsungen, Germany). We aimed to
      investigate the performance of the SGC in medical critically ill patients.
      METHODS: Two open clinical investigations in tertiary centers in Graz, Austria
      and Zurich, Switzerland were performed. Efficacy was assessed by percentage of
      time within the target range (4.4-8.3 mmol/L; primary end point), mean blood
      glucose, and sampling interval. Safety was assessed by the number of hypoglycemic
      episodes (<=2.2 mmol/L) and the percentage of time spent below this cutoff level.
      Usability was analyzed with a standardized questionnaire given to involved
      nursing staff after the trial. RESULTS: Forty medical critically ill patients
      (age, 62 +/- 15 years; body mass index, 30.0 +/- 8.9 kg/m2; APACHE II score, 24.8
      +/- 5.4; 27 males; 8 with diabetes) were included for a period of 6.5 +/- 3.7
      days (n = 20 in each center). The primary endpoint (time in target range 4.4 to
      8.3 mmol/l) was reached in 88.3% +/- 9.3 of the time and mean arterial blood
      glucose was 6.7 +/- 0.4 mmol/l. The sampling interval was 2.2 +/- 0.4 hours. The
      mean daily insulin dose was 87.2 +/- 64.6 IU. The adherence to the given insulin
      dose advice was high (98.2%). While the percentage of time spent in a moderately
      hypoglycemic range (2.2 to 3.3 mmol/L) was low (0.07 +/- 0.26% of the time), one
      severe hypoglycemic episode (<2.2 mmol/L) occurred (2.5% of patients or 0.03% of
      glucose readings). CONCLUSIONS: SGC is a safe and efficient method to control
      blood glucose in critically ill patients as assessed in two European medical
      intensive care units.

PMID- 25074072
TI  - A comparison of multiphasic oral contraceptives containing norgestimate or
      desogestrel in acne treatment: a randomized trial.
AB  - OBJECTIVE: This study aimed to compare the effectiveness and safety of triphasic
      combined oral contraceptives (OCs) containing ethinyl estradiol (EE) and
      norgestimate (NGM) and biphasic combined OCs containing EE and desogestrel (DSG)
      in the treatment of mild to moderate acne. STUDY DESIGN: This was an investigator
      blinded, randomized, parallel group trial conducted at 3 centers in Thailand.
      Female subjects 18-45 years old were assigned to one or the other OCs and
      evaluated for efficacy and safety parameters at the baseline visit and after 1, 3
      and 6 months of treatment. RESULTS: Among 201 randomized subjects, data from 93
      subjects in the EE/NGM group and 95 subjects in the EE/DSG group were analyzed.
      After 6 months of treatment with EE/NGM and EE/DSG, no differences between
      formulations were found for the decrease in total acne lesion counts (74.4% vs.
      65.1%, respectively, p=.070) or facial improvement score. More women using EE/NGM
      showed a decrease in severity of facial seborrhea than those using EE/DSG
      (p=.005). No changes in weight were noted in either group as compared to
      baseline. CONCLUSION: Multiphasic OCs containing EE/NGM and EE/DSG provided
      comparable efficacy and tolerability in the treatment of acne. However, EE/NGM
      had a more beneficial effect on facial seborrhea reduction than EE/DSG.
      IMPLICATIONS: EE/NGM and EE/DSG are multiphasic OCs, which were shown to be
      clinically equally effective for mild to moderate facial acne, and the
      multiphasic combined OC with NGM was more effective for women with facial
      seborrhea. Clinicians may apply the results of this study when considering
      treatment options for facial acne and seborrhea.

PMID- 25074073
TI  - Politicians alienate nurses at their peril.

PMID- 25074074
TI  - RCN honoured for supporting reservists.

PMID- 25074070
TI  - Effect of tree nuts on metabolic syndrome criteria: a systematic review and meta
      analysis of randomised controlled trials.
AB  - OBJECTIVE: To provide a broader evidence summary to inform dietary guidelines of
      the effect of tree nuts on criteria of the metabolic syndrome (MetS). DESIGN: We
      conducted a systematic review and meta-analysis of the effect of tree nuts on
      criteria of the MetS. DATA SOURCES: We searched MEDLINE, EMBASE, CINAHL and the
      Cochrane Library (through 4 April 2014). ELIGIBILITY CRITERIA FOR SELECTING
      STUDIES: We included relevant randomised controlled trials (RCTs) of >=3 weeks
      reporting at least one criterion of the MetS. DATA EXTRACTION: Two or more
      independent reviewers extracted all relevant data. Data were pooled using the
      generic inverse variance method using random effects models and expressed as mean
      differences (MD) with 95% CIs. Heterogeneity was assessed by the Cochran Q
      statistic and quantified by the I(2) statistic. Study quality and risk of bias
      were assessed. RESULTS: Eligibility criteria were met by 49 RCTs including 2226
      participants who were otherwise healthy or had dyslipidaemia, MetS or type 2
      diabetes mellitus. Tree nut interventions lowered triglycerides (MD=-0.06 mmol/L
      (95% CI -0.09 to -0.03 mmol/L)) and fasting blood glucose (MD=-0.08 mmol/L (95%
      CI -0.16 to -0.01 mmol/L)) compared with control diet interventions. There was no
      effect on waist circumference, high-density lipoprotein cholesterol or blood
      pressure with the direction of effect favouring tree nuts for waist
      circumference. There was evidence of significant unexplained heterogeneity in all
      analyses (p<0.05). CONCLUSIONS: Pooled analyses show a MetS benefit of tree nuts
      through modest decreases in triglycerides and fasting blood glucose with no
      adverse effects on other criteria across nut types. As our conclusions are
      limited by the short duration and poor quality of the majority of trials, as well
      as significant unexplained between-study heterogeneity, there remains a need for
      larger, longer, high-quality trials. TRIAL REGISTRATION NUMBER: NCT01630980.

PMID- 25074075
TI  - Threat of industrial action looms as nurses vent their anger on pay.

PMID- 25074076
TI  - L32 for 100 wipes--what a waste of NHS money.

PMID- 25074077
TI  - College becomes an accredited living wage employer.

PMID- 25074078
TI  - Commons committee report recommends scrapping flawed disability benefit.

PMID- 25074079
TI  - Move to make NMC registration fee payable in instalments next year.

PMID- 25074080
TI  - Skydiving jump in aid of bladder scanner.

PMID- 25074081
TI  - Assessment guidance would help staff pinpoint under-fives at risk.

PMID- 25074082
TI  - Hospital trials patient monitoring system.

PMID- 25074084
TI  - Further charges brought in falsification of records case.

PMID- 25074085
TI  - Advice on care of vulnerable people.

PMID- 25074087
TI  - Leading groups unite in bid to improve BME staff prospects.

PMID- 25074089
TI  - Games call-up is triathlete's dream come true.

PMID- 25074090
TI  - More district nurses are qualifying but numbers in NHS still 'eroded'.

PMID- 25074091
TI  - 'That it has come to this shows how angry and frustrated nurses are'.

PMID- 25074097
TI  - Crohn's disease.

PMID- 25074098
TI  - Stoicism and care in the face of carnage.
AB  - Nursing Standard interviews nurse historian Christine Hallett about the nursing
      contribution to the first world war effort. Professor Hallett, author of Veiled
      Warriors, explains the incredible demands placed on nurses who found themselves
      treating vast numbers of casualties with wounds of unprecedented severity.
      Patriotism, a culturally ingrained stoicism and camaraderie between nurses helped
      them get through it.

PMID- 25074099
TI  - Making drugs safe.
AB  - The draft NMC code warns nurses and midwives not to exceed the limits of their
      competence when prescribing, dispensing and administering medicines. The code
      reinforces individuals' responsibilities in this area, but reducing the toll of
      medication errors also requires progress in error reporting and system failures.

PMID- 25074112
TI  - Trusts in trouble need supportive help, not excessive intervention.

PMID- 25074113
TI  - Safe staffing discussions always overlook community nursing.

PMID- 25074114
TI  - The RCN stance on nurses' pay sees to have hit stony ground.

PMID- 25074115
TI  - We should be pushing for a much larger pay rise than 1 per cent.

PMID- 25074117
TI  - Force-feeding people is wrong and nurses should play no part.

PMID- 25074121
TI  - Improving end of life care for people with dementia.
AB  - Nurses caring for older patients across diverse settings will provide care for
      people with dementia approaching the end of their lives. Demographic changes mean
      that the number of people dying with dementia will increase, however nurses and
      other healthcare professionals may be unprepared to meet their needs. Factors
      that are essential to provide compassionate and dignified end of life care for
      people with dementia include effective communication with those with cognitive
      impairment and an awareness of likely causes of anxiety, fear and resistance to
      care when carrying out interventions. Accurate assessment and pain relief are
      required to ensure good end of life care. Knowledge of challenging and complex
      issues around maintenance of nutrition and hydration requirements, and
      communication skills to discuss the issues with families and carers are also
      required. 

PMID- 25074122
TI  - Applying social impact assessment to nursing research.
AB  - Many nurses need to construct a research proposal at some stage of their career
      and there are multiple texts that provide guidance on doing so. However, most
      texts do not provide explicit guidance on the issue of social impact--the effect
      of research on the social health and wellbeing of individuals, families and
      communities and on the improved performance of relevant services. This article
      proposes that social impact should be considered from the beginning of a research
      project. It outlines a framework for assessing social impact to help strengthen
      the quality of research proposals and assist nurses constructing the proposal and
      also those evaluating it, including academic assessors or funding body reviewers.
      Nursing research should be useful and should have a positive effect on practice.
      Focusing on social impact can increase the chances of this desirable outcome.

PMID- 25074123
TI  - Prevention of surgical site infection.
AB  - Surgical site infection (SSI) is a common healthcare-associated infection that
      can cause patients extreme pain and discomfort, resulting in prolonged
      hospitalisation and additional costs to the NHS. Multidisciplinary team working,
      combined with audit and surveillance, early recognition of signs and symptoms of
      infection, and implementation of evidence-based guidance are essential for
      reducing the incidence of SSI. Nurses caring for patients in the pre, peri and
      post-operative period have an important role in advising individuals about the
      risks associated with SSI and how infection should be managed. 

PMID- 25074124
TI  - Ethical practice.

PMID- 25074126
TI  - Tailoring job descriptions.

PMID- 25074125
TI  - South Asian experience.

PMID- 25074127
TI  - A healthy regard for the legal system.

PMID- 25074129
TI  - Putting theory into practice.

PMID- 25074131
TI  - Donor-acceptor alternating copolymer nanowires for highly efficient organic solar
      cells.
AB  - A donor-acceptor conjugated copolymer enables the formation of nanowire systems
      that can be successfully introduced into bulk-heterojunction organic solar cells.
      A simple binary solvent mixture that makes polarity control possible allows
      kinetic control over the self-assembly of the crystalline polymer into a nanowire
      structure during the film-forming process. The enhanced photoconductivity of the
      nanowire-embedded photoactive layer efficiently facilitates photon harvesting in
      the solar cells. The resultant maximum power conversion efficiency is 8.2% in a
      conventional single-cell structure, revealing a 60% higher performance than in
      devices without nanowires. 

PMID- 25074133
TI  - Editorial Comment to Midurethral autologous fascial sling surgery with
      reconstruction of the lower abdominal wall using the tensor fascia lata muscle
      flap for post-hemipelvectomy stress urinary incontinence.

PMID- 25074134
TI  - Editorial.

PMID- 25074132
TI  - Multilevel and geo-statistical modeling of malaria risk in children of Burkina
      Faso.
AB  - BACKGROUND: Previous research on determinants of malaria in Burkina Faso has
      largely focused on individual risk factors. Malaria risk, however, is also shaped
      by community, health system, and climatic/environmental characteristics. The aims
      of this study were: i) to identify such individual, household, community, and
      climatic/environmental risk factors for malaria in children under five years of
      age, and ii) to produce a parasitaemia risk map of Burkina Faso. METHODS: The
      2010 Demographic and Health Survey (DHS) was the first in Burkina Faso that
      tested children for malaria parasitaemia. Multilevel and geo-statistical models
      were used to explore determinants of malaria using this nationally representative
      database. RESULTS: Parasitaemia was collected from 6,102 children, of which 66.0%
      (95% confidence interval (CI): 64.0-68.0%) were positive for Plasmodium spp.
      Older children (>23 months) were more likely to be parasitaemic than younger
      ones, while children from wealthier households and whose mother had higher
      education were at a lower risk. At the community level, living in a district with
      a rate of attendance to health facilities lower than 2 visits per year was
      significantly associated with greater odds of being infected. Malaria prevalence
      was also associated with higher normalized difference vegetation index, lower
      average monthly rainfall, and lower population densities. Predicted malaria
      parasitaemia was spatially variable with locations falling within an 11%-92%
      prevalence range. The number of parasitaemic children was nonetheless
      concentrated in areas of high population density, albeit malaria risk was notably
      higher in the sparsely populated rural areas. CONCLUSION: Malaria prevalence in
      Burkina Faso is considerably higher than in neighbouring countries. Our spatially
      explicit population-based estimates of malaria risk and infected number of
      children could be used by local decision-makers to identify priority areas where
      control efforts should be enhanced.

PMID- 25074135
TI  - Compression, shear and bending on tissue-engineered cartilage: a numerical study.

PMID- 25074136
TI  - Dynamic mesenchymal stem cells volumic seeding in a commercialized porous ceramic
      scaffold: a feasibility study.

PMID- 25074137
TI  - Influence of the alveolar structure on the cell progression in the seeding of
      large bone scaffolds: an in silico study.

PMID- 25074138
TI  - The role of implant's surface treatment to its preload.

PMID- 25074139
TI  - Thoracic aorta morphometry and endograft deployment.

PMID- 25074141
TI  - Left atrium wall tracking from MR images for strain assessment.

PMID- 25074140
TI  - Increase in coronary microvascular resistances after recanalisation with drug
      eluting stent.

PMID- 25074142
TI  - A new finite element method for inverse problems in structural analysis:
      application to atherosclerotic plaque elasticity reconstruction.

PMID- 25074143
TI  - Numerical modelling of the flow of the ultrasound contrast agents in tumour
      microvasculature.

PMID- 25074144
TI  - Numerical simulation of LDL transport through the carotid arterial wall.

PMID- 25074145
TI  - Comparison of different viscoelastic models for the characterisation of
      mechanical properties of human skin in vivo by indentation test.

PMID- 25074146
TI  - Mathematical model of human osteon and its validation by nanomechanical testing
      of bone lamella.

PMID- 25074147
TI  - Biaxial mechanical response of graft material derived from human skin.

PMID- 25074148
TI  - Characterisation of a dedicated mechanical model for red blood cells: numerical
      simulations of optical tweezers experiment.

PMID- 25074149
TI  - Fingertip finite element modelling--on choosing the right material property.

PMID- 25074150
TI  - New magnetic resonance elastography protocols to characterise deep back and thigh
      muscles.

PMID- 25074151
TI  - Effects of bone density in the time-dependent mechanical properties of human
      cortical bone by nanoindentation.

PMID- 25074152
TI  - Time required for an oblate capsule in flow to reach equilibrium.

PMID- 25074153
TI  - Annulus fibrosus microstructure: an explanation to local heterogeneities.

PMID- 25074154
TI  - Compression tests of a living cell: a contact detection problem.

PMID- 25074155
TI  - Investigation of a six-year-old Hybrid III dummy neck stiffness and the
      consequences regarding out-of-position Neck Injury Criteria.

PMID- 25074156
TI  - A methodology to assess non-axial loading on the distal radius.

PMID- 25074157
TI  - Experimental and numerical studies of fluid-structure interaction phenomena
      inside the head when subjected to a dynamical loading.

PMID- 25074158
TI  - Sled acceleration control for low-speed impact testing and transient response
      studies.

PMID- 25074159
TI  - Intermediate strain rate behaviour of cancellous bone: from the lower to the
      higher strain rate.

PMID- 25074160
TI  - A model for micromotion-induced fluid flow at the bone-implant interface.

PMID- 25074161
TI  - Rapid prototyping--a promising technique for orthopaedic implant fabrication:
      application and validation of TKA prototypes for in-vitro testing.

PMID- 25074162
TI  - An innovative method for the three-dimensional study of hip joint motion.

PMID- 25074163
TI  - Finite element investigation of the intervertebral disc behaviour.

PMID- 25074164
TI  - Structural and behavioural analysis of children's cortical bones.

PMID- 25074165
TI  - Biomechanical analysis and modelling of lumbar belt: parametric study.

PMID- 25074166
TI  - Computed tomography morphometric analysis of porcine spinal growth for scoliosis
      model development.

PMID- 25074167
TI  - Influence of age and localisation on pedicle fixation in immature porcine spines.

PMID- 25074168
TI  - In vitro characterisation of the elasticity and the permeability of the mouse
      cartilage during growth using microindentation.

PMID- 25074169
TI  - Numerical simulations in a bony callus.

PMID- 25074170
TI  - Biomechanical analysis of spinal instrumentation systems dedicated to stabilise
      thoracolumbar fractures: comparison between standard open surgical
      instrumentation and percutaneous techniques.

PMID- 25074171
TI  - A framework towards personalisation and active muscle integration in a 3D finite
      element neck model for orthopaedic applications.

PMID- 25074172
TI  - Influence of biomechanical multi-joint models used in global optimisation to
      estimate healthy and osteoarthritis knee kinematics.

PMID- 25074173
TI  - Analysis of mimic facial movements based on motion capture.

PMID- 25074174
TI  - Analysis of ankle stiffness for asymptomatic subjects and transfemoral amputees
      in daily living situations.

PMID- 25074175
TI  - Effect of custom foot orthotics on three-dimensional kinematics and dynamics
      during walking.

PMID- 25074176
TI  - Kinematic model and elbow flexion interaction on shoulder range of motion.

PMID- 25074177
TI  - Biomechanical analysis of interaction strategies using touchscreen: preliminary
      study.

PMID- 25074179
TI  - An upper limb model proposal for multi-body optimisation: effects of anatomical
      constraints on the kinematics.

PMID- 25074178
TI  - What is the most efficient for torque steadiness in young adults: a real-time
      visual feedback of performance or proprioceptive inputs?

PMID- 25074180
TI  - Muscular power as a function of load in elderly women.

PMID- 25074181
TI  - Turning resistance of a manual wheelchair: a theoretical study.

PMID- 25074182
TI  - Estimation of the fingers joint axes of rotation in flexion-extension.

PMID- 25074183
TI  - How do healthy older pedestrians walk when they cross the street?

PMID- 25074184
TI  - Unipodal landing in individuals with unilateral chronic ankle instability.

PMID- 25074185
TI  - The contribution of handgrip assistance on lower limb joint moments during sit-to
      stand and stand-to-sit: a preliminary comparative study.

PMID- 25074186
TI  - Walking efficiency in children with cerebral palsy: relation to muscular strength
      and gait parameters.

PMID- 25074187
TI  - Articulated vs. fixed carbon-fibre prosthesis after transmetatarsial amputation:
      a case study.

PMID- 25074188
TI  - Benefits of functional calibration for estimating elbow joint angles using
      magneto-inertial sensors: preliminary results.

PMID- 25074189
TI  - Determination of vertical ground reaction forces under each foot during walking.

PMID- 25074190
TI  - Knee crosstalk is not a quality indicator of the hip rotation.

PMID- 25074191
TI  - Small cause, great impact: a sensitivity study in musculoskeletal modelling of
      the hand.

PMID- 25074192
TI  - Effect of vibration frequency and angle knee flexion on muscular activity and
      transmissibility function during static whole body vibration exercise.

PMID- 25074193
TI  - Impact of partial-thickness tears on supraspinatus tendon strain based on a
      finite element analysis.

PMID- 25074194
TI  - In vivo cervical intervertebral disc characterisation by elastography.

PMID- 25074195
TI  - Optimisation technique of camera placement for motion capture simulations.

PMID- 25074196
TI  - A qualitative analysis of soft tissue artefact during running.

PMID- 25074197
TI  - Functionally computed flexion axis reduces kinematic interspecimen variation in
      in vitro experiments.

PMID- 25074198
TI  - Analysis of long-range autocorrelation series: effect of the number of cycles on
      statistical precision and sensitivity.

PMID- 25074200
TI  - Introduction of a set of EMG-based muscular activations in a multi-objective
      optimisation when solving the muscular redundancy problem during gait.

PMID- 25074199
TI  - Effects of glenohumeral joint centre mislocation on shoulder kinematics and
      kinetics.

PMID- 25074201
TI  - Tensile response of the muscle-tendon complex using discrete element model.

PMID- 25074202
TI  - Comparison of two MRI sequences for subject-specific 3D thigh muscle
      reconstruction.

PMID- 25074203
TI  - A method to study 3D knee pseudo-kinematics using low-dose stereoradiography
      during static squat.

PMID- 25074204
TI  - Shuttlecock velocity during a smash stroke in badminton evolves linearly with
      skill level.

PMID- 25074205
TI  - 3D Measurement of the displacement of the forelimb hoof during stance in three
      horses circling at the canter on a competition surface.

PMID- 25074206
TI  - Effects of speed on the vertical amplitude of the stride in trotters--comparison
      between fore- and hindlimbs, and influence of the track surface.

PMID- 25074207
TI  - Effects of footwear midsole hardness on females' lower limb kinetics and
      kinematics during cutting manoeuvres.

PMID- 25074208
TI  - Transmission of whole-body vibration to lower limb during dynamic squat exercise.

PMID- 25074209
TI  - Methodological contribution to study the vibratory behaviour of tennis rackets
      following real forehand drive impact.

PMID- 25074210
TI  - Influence of racket on the variability of humerothoracic joint kinematics during
      tennis serve: a preliminary study.

PMID- 25074211
TI  - Bilateral comparison of scapulothoracic kinematics during scaption in girl tennis
      players.

PMID- 25074212
TI  - Swimming drafting simulation using a k-omega turbulence model.

PMID- 25074213
TI  - Muscle coordination in loaded squat jump.

PMID- 25074214
TI  - Validation of a low-cost wearable accelerometer for temporal gait parameter
      quantification.

PMID- 25074215
TI  - Analysis of 3D motion patterns with self-organising maps (SOM) and statistical
      parametric mapping (SPM): a methodological proposal.

PMID- 25074216
TI  - A preliminary study on the realism of digital human manikins used for ergonomics
      simulation.

PMID- 25074217
TI  - Combined experimental and numerical approach for the assessment of pressure
      generated by elastic compression bandage.

PMID- 25074218
TI  - Is the kinematic of the trunk during the forehand in tennis still disrupted in
      women at one year postpartum?

PMID- 25074219
TI  - Analysis biomechanics of the 3D angle of the upper limb: study of manual
      wheelchair obstacle climbing.

PMID- 25074220
TI  - Does handle shape influence prehensile capabilities and muscle coordination?

PMID- 25074221
TI  - A bio-inspired limb controller for avatar animation.

PMID- 25074222
TI  - Assessment of a numerical model of balance recovery by stepping.

PMID- 25074223
TI  - ARMA modelling and nonparametric probability density function of gait signal
      using L2-L1 estimator in patients with neurodegenerative disease.

PMID- 25074224
TI  - Contrasted mediolateral postural control mechanisms in varied foot positions.

PMID- 25074225
TI  - Validity of a low-cost wearable device for body sway parameter evaluation.

PMID- 25074226
TI  - Behaviour of the muscle-tendon unit of the gastrocnemius medialis and tibialis
      anterior during forward and backward sways.

PMID- 25074227
TI  - Adapted physical activity intervention and vestibular disorders.

PMID- 25074228
TI  - Design of an assistant robot for alignment of fractured bones in medical
      operations.

PMID- 25074229
TI  - Finite element modelling of nearly incompressible materials and volumetric
      locking: a case study.

PMID- 25074233
TI  - Transcatheter aortic valve implantation using a direct aortic approach: a single
      centre Heart Team experience.
AB  - OBJECTIVES: The transaortic (TAo) approach has been introduced as an alternative
      to transapical and transaxillary aortic valve implantation for patients with
      symptomatic severe aortic stenosis in whom a transfemoral approach is not
      feasible. However, only very limited data from a minimal number of specialized
      centres are available on this approach. Therefore, the aim of this study was to
      evaluate the early postoperative 30-day outcomes of the direct aortic approach
      performed by a single-centre multidisciplinary Heart Team. METHODS: Between May
      2011 and July 2013, 159 patients underwent transcatheter aortic valve
      implantation (TAVI) at our institution; of which, 44 were believed to benefit
      most from the TAo as assessed by a multidisciplinary Heart Team. All patients
      underwent an upper 'J' median hemi-sternotomy through a 6-cm incision. The
      evaluation of early operative results was made according to the Valve Academic
      Research Consortium (VARC) consensus criteria. These include device success
      endpoints and combined safety endpoints at 30 days. RESULTS: The mean age of the
      patients was 78 years, the mean logistic EuroSCORE was 25.9 +/- 14.4% and the
      mean Society of the Thoracic Surgeons score 5.8 +/- 4.5%. Seventeen patients
      (39%) underwent redo operations; 4 (9%) received a transcatheter valve in a
      degenerated bioprosthesis. The procedure was performed using the Medtronic
      CoreValve Revalving system in 36 patients, with the Edwards SAPIEN XT in 7 cases
      and the St Jude Medical Portico valve in 1. Device success was achieved in 90.8%
      of the cases. Complications included; major stroke (n = 1), re-exploration for
      cardiac tamponade (n = 3), transient renal failure requiring temporary
      haemodialysis (n = 1) and permanent pacemaker implantation (n = 5). There were no
      myocardial infarctions. The total 30-day mortality rate was 6.8% (3 patients).
      Postoperative intensive care unit stay was 2.6 +/- 3.6 days, and the mean
      hospitalization was 12 +/- 9.6 days. CONCLUSIONS: The TAo TAVI approach is
      feasible and offers a safe alternative for patients in whom a transfemoral
      approach is not feasible or desirable.

PMID- 25074230
TI  - Regenerative responses after mild heart injuries for cardiomyocyte proliferation
      in zebrafish.
AB  - BACKGROUND: The zebrafish heart regenerates after various severe injuries. Common
      processes of heart regeneration are cardiomyocyte proliferation, activation of
      epicardial tissue, and neovascularization. In order to further characterize heart
      regeneration processes, we introduced milder injuries and compared responses to
      those induced by ventricular apex resection, a widely used injury method. We used
      scratching of the ventricular surface and puncturing of the ventricle with a fine
      tungsten needle as injury-inducing techniques. RESULTS: Scratching the
      ventricular surface induced subtle cardiomyocyte proliferation and responses of
      the epicardium. Endothelial cell accumulation was limited to the surface of the
      heart. Ventricular puncture induced cardiomyocyte proliferation, endocardial and
      epicardial activation, and neo-vascularization, similar to the resection method.
      However, the degree of the responses was milder, correlating with milder injury.
      Sham operation induced epicardial aldh1a2 expression but not tbx18 and WT1.
      CONCLUSIONS: Puncturing the ventricle induces responses equivalent to resection
      at milder degrees in a shorter time frame and can be used as a simple injury
      model. Scratching the ventricle did not induce heart regeneration and can be used
      for studying wound responses to epicardium.

PMID- 25074234
TI  - Performance of acute flaccid paralysis surveillance compared with World Health
      Organization standards.
AB  - AIM: To compare acute flaccid paralysis (AFP) surveillance systems used by
      members of the International Network of Paediatric Surveillance Units (INoPSU)
      across the five AFP surveillance performance indicators recommended by the World
      Health Organization (WHO) for the maintenance of polio-free certification.
      METHODS: A survey was administered to AFP surveillance co-ordinators in five
      INoPSU member countries (Australia, Belgium, Canada, New Zealand and
      Switzerland). Data collected included information on surveillance system
      processes, WHO-recommended performance indicators, investigative practices and
      final diagnoses of cases from 2006 to 2010. RESULTS: All countries contacted
      completed the survey. Each country used similar case definitions and processes
      for collecting AFP data. All countries used at least one of the WHO indicators
      for surveillance. No country consistently met the performance indicator for
      incidence or stool sampling. In all countries, at least one form of neurological
      testing was used to diagnose cases of AFP. Guillain-Barre syndrome was the most
      common final diagnosis in all countries for all years examined. CONCLUSIONS:
      Industrialised countries surveyed do not consistently meet the WHO-recommended
      AFP surveillance performance indicators. An opportunity exists for INoPSU to
      suggest a standard way for member countries to collect AFP data in order to
      examine the potential for strengthening the current systems or introducing
      additional enterovirus surveillance or alternative/complementary neurological
      performance measures suitable for countries that have eliminated polio. INoPSU
      member countries are evaluating these possibilities.

PMID- 25074235
TI  - Foreign body granuloma secondary to ventriculo-peritoneal shunt: a rare scenario
      with a new insight.
AB  - Ventriculo-peritoneal shunts are used extensively for the management of
      hydrocephalus and frequently present with complications such as shunt blockage
      and infection. Cerebrospinal fluid (CSF) eosinophilia and allergic responses to
      the shunt itself are rare, poorly understood but increasingly recognised
      complications. Here, the authors describe a child who required multiple shunt
      revision surgeries due to extensive scalp tenderness overlying the shunt tubing
      and persistent severe headaches despite having a normal working shunt and no CSF
      infection or eosinophilia. Histological investigation of excised tissue during
      the last shunt revision demonstrated fibrosis with scar tissue and chronic
      inflammatory infiltrate with foreign body giant cells and few abortive
      granulomata. This was felt to represent a foreign body reaction to the shunt. A
      hypoallergenic 'extracted' shunt was trialled (extracted Delta(r) valve and
      extracted ventricular and peritoneal catheters; Medtronic) and the child has had
      no further shunt revisions and is currently asymptomatic 1 year after the
      insertion.

PMID- 25074236
TI  - Effects of FlrBC on flagellar biosynthesis of Shewanella oneidensis.
AB  - As a most conserved complex molecular machine made up of a large number of
      structural subunits, the flagellum is under tight regulation by hierarchical
      arrangements. Although variations in polar flagellar systems are found, most of
      them are restricted to multiple-copy components, such as flagellins and stators.
      Therefore, these features are regarded to be peripheral relative to the
      comprehensive conservation. In this study, however, we present evidence to show
      that the difference in highly conserved polar flagellar systems can be
      surprisingly profound, even at the heart of the classical regulatory hierarchy.
      In Gram-negative Shewanella oneidensis, two-component system FlrBC, whose
      counterpart is essential for flagellar biosynthesis and motility by directly
      controlling expression of class III genes in polarly flagellated bacteria such as
      Vibrio cholerae, is dispensable for the process. The system directly controls
      expression of the flaA gene, encoding a flagellin of weak motility. We further
      show that the ratio of two flagellins, FlaA and FlaB, determines motility of a
      flagellum. More strikingly, overproduction of FlrC results in a peritrichously
      multi-flagellated phenotype, and FlrC is likely to function as an activator in
      its unphosphorylated form for transcription of the flaA gene, contrasting the
      previously characterized counterpart. 

PMID- 25074238
TI  - Focused ion beam lithography for fabrication of suspended nanostructures on
      highly corrugated surfaces.
AB  - We propose a nanofabrication method that allows for patterning on extremely
      corrugated surfaces with micrometer-size features. The technique employs focused
      ion beam nanopatterning of ion-sensitive inorganic resists formed by atomic layer
      deposition at low temperature. The nanoscale resolution on corrugated surfaces is
      ensured by inherently large depth of focus of a focused ion beam system and very
      uniform resist coating. The utilized TiO2 and Al2O3 resists show high selectivity
      in deep reactive ion etching and enable the release of suspended nanostructures
      by dry etching. We demonstrate the great flexibility of the process by
      fabricating suspended nanostructures on flat surfaces, inclined walls, and on the
      bottom of deep grooves.

PMID- 25074237
TI  - Early primary care provider follow-up and readmission after high-risk surgery.
AB  - IMPORTANCE: Follow-up with a primary care provider (PCP) in addition to the
      surgical team is routinely recommended to patients discharged after major surgery
      despite no clear evidence that it improves outcomes. OBJECTIVE: To test whether
      PCP follow-up is associated with lower 30-day readmission rates after open
      thoracic aortic aneurysm (TAA) repair and ventral hernia repair (VHR), surgical
      procedures known to have a high and low risk of readmission, respectively.
      DESIGN, SETTING, AND PARTICIPANTS: In a cohort of Medicare beneficiaries
      discharged to home after open TAA repair (n = 12 679) and VHR (n = 52 807)
      between 2003 to 2010, we compared 30-day readmission rates between patients seen
      and not seen by a PCP within 30 days of discharge and across tertiles of regional
      primary care use. We stratified our analysis by the presence of complications
      during the surgical (index) admission. MAIN OUTCOMES AND MEASURES: Thirty-day
      readmission rate. RESULTS: Overall, 2619 patients (20.6%) undergoing open TAA
      repair and 4927 patients (9.3%) undergoing VHR were readmitted within 30 days
      after surgery. Complications occurred in 4649 patients (36.6%) undergoing open
      TAA repair and 4528 patients (8.6%) undergoing VHR during their surgical
      admission. Early follow-up with a PCP significantly reduced the risk of
      readmission among open TAA patients who experienced perioperative complications,
      from 35.0% (without follow-up) to 20.4% (with follow-up) (P < .001). However, PCP
      follow-up made no significant difference in patients whose hospital course was
      uncomplicated (19.4% with follow-up vs 21.9% without follow-up; P = .31). In
      comparison, early follow-up with a PCP after VHR did not reduce the risk of
      readmission, regardless of complications. In adjusted regional analyses,
      undergoing open TAA repair in regions with high compared with low primary care
      use was associated with an 18% lower likelihood of 30-day readmission (odds
      ratio, 0.82; 95% CI, 0.71-0.96; P = .02), whereas no significant difference was
      found among patients after VHR. CONCLUSIONS AND RELEVANCE: Follow-up with a PCP
      after high-risk surgery (eg, open TAA repair), especially among patients with
      complications, is associated with a lower risk of hospital readmission. Patients
      undergoing lower-risk surgery (eg, VHR) do not receive the same benefit from
      early PCP follow-up. Identifying high-risk surgical patients who will benefit
      from PCP integration during care transitions may offer a low-cost solution toward
      limiting readmissions.

PMID- 25074240
TI  - Poland syndrome: an algorithm to select the appropriate chest wall surgical
      reconstructive treatment.
AB  - AIM: Poland syndrome is a constellation of rare congenital anomalies of the chest
      wall, with or without alterations to the ipsilateral superior extremity. Actually
      Foucras' classification is commonly used to choose the most appropriate surgical
      treatment, but often only a radiological classification proves unsatisfactory in
      order to achieve the best aesthetic result. MATERIAL AND METHODS: Since November
      2006 in our institute have been treated 6 patients (3 M, 3 F) with Poland
      Syndrome affected by only chest wall and/or breast deformities. RESULTS: We
      treated 6 patients opting for different surgical procedures, depending on the
      deformity detected. We experienced only one procedural complication, a fat
      necrosis with superior migration of the prosthesis, successfully managed.
      DISCUSSION: Surgical alternative treatments of the Poland's abnormalities of the
      chest wall are independent from the corrective surgery of the ipsilateral
      affected forearm ad hand. Surgeons should be able to develop an operative plan to
      address aesthetic goals while preserving muscular functionality. Indeed surgical
      techniques should be minimally invasive and possible available in every hospital
      structure. CONCLUSIONS: This study has been designed to review a series of
      surgical options of breast reconstruction in patients with Poland Syndrome in
      order to develop a new flow chart to plan the best surgical choice analyzing only
      breast/chest wall deformities according to Blondeel's point of view about
      reconstruction of the new breast and thoracic wall. KEY WORDS: Breast
      reconstruction, Poland syndrome.

PMID- 25074241
TI  - Evaluating the influence of septic systems and watershed characteristics on
      stream faecal pollution in suburban watersheds in Georgia, USA.
AB  - AIMS: To determine the impact of septic systems on water quality and in so doing
      identify watershed level characteristics that influence septic system impact.
      METHODS AND RESULTS: Water samples were collected from streams in 24 well
      characterized watersheds during baseflow to analyse for the levels of faecal
      indicators Escherichia coli and enterococci. The watersheds represent a gradient
      of land-use conditions from low to high density of septic systems, as well as
      developed to undeveloped uses. Our findings indicate statistically significant
      interaction between septic density and season for enterococci count (P = 0.005)
      and stream yield (P = 0.04). Seasonal variations in bacterial count and stream
      yield were also observed, with significant differences between spring-winter and
      summer-winter. Results from multiple linear regression models suggest that
      watershed characteristics (septic system density, median distance of septic
      systems to stream, per cent developed area and forest cover) and water
      temperature could explain approximately half (R(2) = 0.50) of the variability in
      bacterial count and yield in spring and summer. CONCLUSIONS: There is a
      significant positive relationship between septic system density and faecal
      pollution levels. However, this relationship is season dependent and is
      influenced by watershed level characteristics such as median distance of septic
      systems from streams, per cent developed area and forest cover. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study confirms the significant impact of septic systems
      on faecal pollution during baseflow and provides the tools that will enable
      effective pollution monitoring at the watershed scale.

PMID- 25074242
TI  - Speed control for neuronal migration in the postnatal brain by Gmip-mediated
      local inactivation of RhoA.
AB  - Throughout life, new neurons generated in the ventricular-subventricular zone
      take the long journey to the olfactory bulb. The intracellular mechanisms that
      precisely control the neurons' migration speed, enabling their well-organized
      movement, remain unclear. Rho signalling is known to affect the morphology and
      movement of various cell types, including neurons. Here we identify Gem
      interacting protein (Gmip), a RhoA-specific GTPase-activating protein, as a key
      factor in saltatory neuronal migration. RhoA is activated at the proximal leading
      process of migrating neurons, where Gmip is also localized and negatively
      regulates RhoA. Gmip controls the saltatory movement of neurons that regulate
      their migration speed and 'stop' positions in the olfactory bulb, thereby
      altering the neural circuitry. This study demonstrates that Gmip serves as a
      brake for the RhoA-mediated movement of neuronal somata, and highlights the
      significance of speed control in the well-organized neuronal migration and the
      maintenance of neuronal circuits in the postnatal brain. 

PMID- 25074243
TI  - Dental practitioner rural work movements: a systematic review.
AB  - INTRODUCTION: There is a globally observed unequal distribution of dental and
      other health practitioners between urban and rural areas in OECD countries.
      Dental practitioners provide important primary healthcare services to rural
      populations. Workforce shortages and stability issues in underserved areas can
      have negative effects on rural communities. Strategies used to fix the dental
      practitioner workforce maldistribution need to be investigated. METHOD: The study
      had primary focus on Australia and included relevant international literature.
      Databases used were PubMed, Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), Informit, Web of Science, Scopus and Summon. Search terms
      included dental practitioner, rural, remote, retention, recruitment and
      strategies. RESULTS: Sixteen articles met the inclusion criteria. The articles
      described a total of eight different positive factors and 12 negative factors
      towards rural practice. The positive factors related to the nature of the type of
      clinical work being a 'challenge', close social and professional support
      networks, enjoyment of rural lifestyle and successful integration into the rural
      community. The negative factors mentioned included social and professional
      isolation, workload and type of clinical work, access to further education
      opportunities, access to facilities, education for children and job opportunities
      for a partner, and inability to integrate into the rural community. The articles
      that analysed recruitment incentives described three strategies currently used to
      influence recruitment, all of which were financial or contractual in nature.
      Articles mentioning retention factors described seven long-term retention
      motivators; of these, six of them were personal reasons. The most commonly
      mentioned motivational factor for recruitment and retention of the rural dental
      practitioner workforce was the effect of prior rural exposure for dental
      practitioners. CONCLUSIONS: The results of this review indicate that the most
      important influences on rural dental practitioner workforce recruitment and
      retention were a combination of financial reimbursement and personal reasons.
      There was also a large influence of rural medical workforce research on untested
      assumptions and drivers of the rural dental practitioner workforce. The high
      recruitment rate compared with the low retention rate indicates that current
      strategies were not effective in addressing rural dental practitioner workforce
      shortages in the long term.

PMID- 25074244
TI  - Effect of interleukin-4 on orthodontic tooth movement and associated root
      resorption.
AB  - OBJECTIVES: Interleukin-4 (IL-4) is a recognized immunomodulatory cytokine that
      regulates bone homeostasis. However, the influence of IL-4 on orthodontic tooth
      movement (OTM) and subsequent root resorption is still unknown. Therefore, the
      purpose of this study was to investigate the effect of IL-4 on tooth movement and
      its associated root resorption in a mouse model. MATERIALS AND METHODS: The
      maxillary first molars of four male mice for each experimental group were
      subjected to mesial force by a nickel titanium coil spring for 12 days. Control
      mice were not given appliances and injections. Varying doses of IL-4 were
      injected locally, adjacent to the first molar. Two sets of experiments were
      designed. The first set was composed of three groups: the control, treatment with
      phosphate-buffered saline (PBS), or 1.5 ug/day of IL-4. The second set was
      composed of five groups: the control, treatment with 0 (PBS only), 0.015, 0.15,
      or 1.5 ug/day of IL-4. The distance of OTM was measured and tartrate-resistant
      acid phosphatase positive cells along the loaded alveolar bone and root surface
      were identified. The root resorption associated with OTM was evaluated by a
      scanning electron microscope. RESULTS: The amount of OTM and the number of
      osteoclasts were significantly decreased in the IL-4-treated mice. Moreover, IL-4
      significantly suppressed force-induced odontoclasts and root resorption.
      CONCLUSION: IL-4 inhibits tooth movement and prevents root resorption in the
      mouse model. These results suggest that IL-4 could be used as a useful adjunct to
      regulate the extent of OTM and also to control root resorption.

PMID- 25074245
TI  - Virus-induced gene silencing reveals control of reactive oxygen species
      accumulation and salt tolerance in tomato by gamma-aminobutyric acid metabolic
      pathway.
AB  - gamma-Aminobutyric acid (GABA) accumulates in many plant species in response to
      environmental stress. However, the physiological function of GABA or its
      metabolic pathway (GABA shunt) in plants remains largely unclear. Here, the
      genes, including glutamate decarboxylases (SlGADs), GABA transaminases (SlGABA
      Ts) and succinic semialdehyde dehydrogenase (SlSSADH), controlling three steps of
      the metabolic pathway of GABA, were studied through virus-induced gene silencing
      approach in tomato. Silencing of SlGADs (GABA biosynthetic genes) and SlGABA-Ts
      (GABA catabolic genes) led to increased accumulation of reactive oxygen species
      (ROS) as well as salt sensitivity under 200 mm NaCl treatment. Targeted
      quantitative analysis of metabolites revealed that GABA decreased and increased
      in the SlGADs- and SlGABA-Ts-silenced plants, respectively, whereas succinate
      (the final product of GABA metabolism) decreased in both silenced plants.
      Contrarily, SlSSADH-silenced plants, also defective in GABA degradation process,
      showed dwarf phenotype, curled leaves and enhanced accumulation of ROS in normal
      conditions, suggesting the involvement of a bypath for succinic semialdehyde
      catabolism to gamma-hydroxybutyrate as reported previously in Arabidopsis, were
      less sensitive to salt stress. These results suggest that GABA shunt is involved
      in salt tolerance of tomato, probably by affecting the homeostasis of metabolites
      such as succinate and gamma-hydroxybutyrate and subsequent ROS accumulation under
      salt stress. 

PMID- 25074246
TI  - Patterns of use and tolerance of anti-epidermal growth factor receptor antibodies
      in older adults with metastatic colorectal cancer.
AB  - BACKGROUND: Limited data are available regarding the tolerance of anti-epidermal
      growth factor receptor (EGFR) antibodies among elderly patients with metastatic
      colorectal cancer (mCRC). We retrospectively reviewed our experience of treating
      elderly patients with mCRC with these agents between 2004 and 2011. METHODS:
      Patients with mCRC >= 65 years treated with anti-EGFR agents were included in
      this analysis. We recorded demographic and disease characteristics, treatment
      regimen and duration, KRAS status, and overall survival (OS). Toxicity evaluation
      included common hematologic and nonhematologic toxicities seen with these agents.
      RESULTS: One hundred seventeen patients were included, with a median age at
      treatment initiation of 73 years (range, 65-86 years), 59% of male sex, 82% with
      colon primary tumors, and 51% with metastatic disease at presentation. Median
      time on anti-EGFR treatment was 2.4 months. Older age at treatment initiation was
      associated with use of anti-EGFR antibody as monotherapy versus combination
      therapy (P = .0009). Worse performance status (PS) at treatment initiation was
      associated with a shorter overall survival (OS) (P = .013) and shorter treatment
      duration (P = .01). The incidence of hematologic/nonhematologic grade >= 3 was
      36% and 15%, respectively. No association was found between age and presence of
      grade >= 3 toxicity. Longer treatment duration and better PS at treatment
      initiation were the only factors associated with higher incidence of grade 3
      toxicity. CONCLUSION: Our data demonstrate that anti-EGFR antibodies can be used
      in older patients with mCRC, with toxicity profiles similar to those reported in
      large phase III studies of younger patients. Advanced age was associated with
      receipt of anti-EGFR agents as monotherapy but did not impact treatment outcomes
      in this population.

PMID- 25074247
TI  - ABL1 gene involvement within a complex three-way translocation (2;9;4) in
      perineurioma characterized by molecular cytogenetic methods.
AB  - Perineuriomas are rare peripheral nerve sheath tumors with one or few chromosomal
      rearrangements or numerical changes. Two main types and three subtypes have been
      defined but with few specific genetic associations. Chromosome 10 aberrations
      have been found in three cases of the sclerosing perineurioma subtype. Chromosome
      22 abnormalities have been described in different types of perineurioma. None of
      these aberrations has been described at the molecular level. We report on a
      complex rearrangement characterized by fluorescence in situ hybridization and
      array-comparative genome hybridization, which revealed submicroscopic deletions
      at 2p23 and 9q34 that involved the ABL1 gene in a soft tissue perineurioma case.

PMID- 25074248
TI  - Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute
      myeloid leukemia after hematopoietic cell transplantation.
AB  - The acquisition of the Philadelphia chromosome (Ph) as a secondary change during
      the course of hematopoietic malignancies is rare and is associated with poor
      prognosis. Few cases of secondary Ph have been reported after hematopoietic cell
      transplantation (HCT). A secondary Ph at relapse is of clinical importance
      because it provides a therapeutic target for tyrosine kinase inhibitors along
      with or in replacement of chemotherapy. We describe a case of relapsed acute
      myeloid leukemia (AML) after HCT that developed a BCR-ABL1 translocation along
      with erythrophagocytosis by blasts as a secondary change at the time of relapse.
      The progression of this patient's myeloid neoplasm from myelodysplastic syndrome
      to AML to relapsed AML after HCT was accompanied by a stepwise cytogenetic
      evolution: A deletion 20q abnormality subsequently acquired a deletion 7q and,
      finally, at relapse after HCT, a secondary Ph was gained. The relationship
      between the secondary Ph and the erythrophagocytosis by blasts is not clear. We
      review the possible pathogenesis and cytogenetic associations of
      erythrophagocytosis by blasts, a rare feature in acute leukemias. 

PMID- 25074249
TI  - Plantarflexion moment is a contributor to step length after-effect following
      walking on a split-belt treadmill in individuals with stroke and healthy
      individuals.
AB  - OBJECTIVE: To assess plantarflexion moment and hip joint moment after-effects
      following walking on a split-belt treadmill in healthy individuals and
      individuals post-stroke. DESIGN: Cross-sectional study. SUBJECTS: Ten healthy
      individuals (mean age 57.6 years (standard deviation; SD 17.2)) and twenty
      individuals post-stroke (mean age 49.3 years (SD 13.2)). METHODS: Participants
      walked on an instrumented split-belt treadmill under 3 gait periods: i) baseline
      (tied-belt); ii) adaptation (split-belt); and iii) post-adaptation (tied-belt).
      Participants post-stroke performed the protocol with the paretic and nonparetic
      leg on the faster belt when belts were split. Kinematic data were recorded with
      the Optotrak system and ground reaction forces were collected via the
      instrumented split-belt treadmill. RESULTS: In both groups, the fast
      plantarflexion moment was reduced and the slow plantarflexion moment was
      increased from mid-stance to toe-off in the post-adaptation period. Significant
      relationships were found between the plantarflexion moment and contralateral step
      length. CONCLUSION: Split-belt treadmills could be useful for restoring step
      length symmetry in individuals post-stroke who present with a longer paretic step
      length because the use of this type of intervention increases paretic
      plantarflexion moments. This intervention might be less recommended for
      individuals post-stroke with a shorter paretic step length because it reduces the
      paretic plantarflexion moment.

PMID- 25074251
TI  - Does metabolic syndrome worsen systolic dysfunction in diabetes? The shortwave
      study.
AB  - Patients with metabolic syndrome (MetS) have high cardiovascular event rates. The
      additional effect of MetS on left ventricular (LV) systolic function in patients
      with type 2 diabetes mellitus (T2DM) is unknown. We studied the relation between
      MetS and LV systolic function in T2DM patients without coronary artery disease
      (CAD). Clinical and echocardiographic data from 331 T2DM patients were analyzed.
      Prevalence of MetS was assessed based on NCEP ATPIII definition. Stress-corrected
      midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were
      analyzed as indexes of circumferential and longitudinal shortening, respectively.
      Sc-MS was impaired if <89 %, S' if <8.5 cm/s (10th percentile of healthy
      controls). MetS was diagnosed in 172 patients. Sc-MS and S' were similar in T2DM
      patients with and without MetS (91 +/- 14 vs 92 +/- 15 %; 9.8 +/- 2.0 vs 9.5 +/-
      2.1 cm/s, respectively; p = ns) but significantly reduced comparing to controls
      (102 +/- 11 % and 10.8 cm/s; p < 0.0001). Impairment of sc-MS and S' were
      detected in 37 vs 40 % and in 29 vs 32 % of T2DM patients with and without MetS
      (p = ns), respectively. LV systolic function measured as sc-MS and S' is
      frequently impaired in T2DM patients without CAD; however, the coexistence of
      MetS is not associated with more severe LV systolic dysfunction. Further
      pathological mechanisms have to be considered to explain the negative prognostic
      impact of MetS in T2DM patients.

PMID- 25074250
TI  - The protein transportation pathway from Golgi to vacuoles via endosomes plays a
      role in enhancement of methylmercury toxicity.
AB  - Methylmercury causes serious damage to the central nervous system, but the
      molecular mechanisms of methylmercury toxicity are only marginally understood. In
      this study, we used a gene-deletion mutant library of budding yeast to conduct
      genome-wide screening for gene knockouts affecting the sensitivity of
      methylmercury toxicity. We successfully identified 31 genes whose deletions
      confer resistance to methylmercury in yeast, and 18 genes whose deletions confer
      hypersensitivity to methylmercury. Yeast genes whose deletions conferred
      resistance to methylmercury included many gene encoding factors involved in
      protein transport to vacuoles. Detailed examination of the relationship between
      the factors involved in this transport system and methylmercury toxicity revealed
      that mutants with loss of the factors involved in the transportation pathway from
      the trans-Golgi network (TGN) to the endosome, protein uptake into the endosome,
      and endosome-vacuole fusion showed higher methylmercury resistance than did wild
      type yeast. The results of our genetic engineering study suggest that this
      vesicle transport system (proteins moving from the TGN to vacuole via endosome)
      is responsible for enhancing methylmercury toxicity due to the interrelationship
      between the pathways. There is a possibility that there may be proteins in the
      cell that enhance methylmercury toxicity through the protein transport system. 

PMID- 25074252
TI  - Aspirin reload before elective percutaneous coronary intervention: impact on
      serum thromboxane b2 and myocardial reperfusion indexes.
AB  - BACKGROUND: Microvascular obstruction seems to predict poor outcome in patients
      undergoing elective percutaneous coronary intervention (PCI), but the underlying
      mechanism is still unclear. We analyzed whether serum thromboxane B2, a stable
      metabolite of thromboxane A2, may be implicated in post-PCI microvascular
      obstruction. METHODS AND RESULTS: We enrolled 91 patients (74 males, 66+/-10
      years) on chronic low-dose aspirin therapy (aspirin, 100 mg daily) scheduled for
      elective PCI and randomly assigned to receive aspirin reload (325 mg orally,
      n=46) or no reload (control group, n=45) >=1 hour before elective PCI. Serum
      levels of thromboxane B2, reperfusion indexes (corrected Thrombolysis In
      Myocardial Infarction frame count and myocardial blush grade), and serum cardiac
      troponin I were assessed before and after PCI. Serum thromboxane B2 significantly
      increased after 120 minutes (P=0.0447) from PCI in control but not in aspirin
      reload group. After PCI, both groups showed a statistically significant reduction
      in corrected Thrombolysis In Myocardial Infarction frame count more evident in
      aspirin reload group (P=0.0023). Moreover, after PCI, 61% of patients allocated
      to aspirin reload and only 32% of patients allocated to control group reached
      normal microcirculatory reperfusion (myocardial blush grade=3); patients with
      myocardial blush grade=3 exhibited lower values of serum thromboxane B2 compared
      with those with myocardial blush grade <3 (P=0.05). Periprocedural cardiac
      troponin I significantly increased (F=3.64; P=0.01334) and correlated with serum
      thromboxane B2 (rho=0.31; P=0.0413) in control but not in aspirin reload group.
      In addition, left ventricular ejection fraction significantly increased after PCI
      only in the aspirin reload group (P=0.0005). CONCLUSIONS: Aspirin loading dose
      before elective PCI improves myocardial reperfusion and injury indexes,
      suggesting a possible role of platelet thromboxane A2 in microvascular occlusion.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01374698.

PMID- 25074253
TI  - Incidence and outcome of surgical procedures after coronary artery bypass
      grafting compared with those after percutaneous coronary intervention: a report
      from the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG
      Registry Cohort-2.
AB  - BACKGROUND: Noncardiac surgery after percutaneous coronary intervention (PCI) has
      been reported to be carrying high risk for both ischemic and bleeding
      complications. However, there has been no report comparing the incidence and
      outcomes of surgical procedures after coronary artery bypass grafting (CABG) with
      those after PCI. METHODS AND RESULTS: Among 14 383 patients undergoing first
      coronary revascularization (PCI, n=12 207; CABG, n=2176) enrolled in the Coronary
      Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/CABG
      Registry Cohort-2, surgical procedures were performed more frequently after CABG
      (n=560) than after PCI (n=2398; cumulative 3-year incidence: 27% versus 22%;
      unadjusted P<0.0001), particularly <6 months of coronary revascularization. The
      risk for the primary ischemic outcome measure (death/myocardial infarction) at 30
      day postsurgical procedures was not significantly different between the CABG and
      PCI groups (cumulative incidence: 3.1% versus 3.2%; unadjusted P=0.9; adjusted
      hazard ratio, 0.97; 95% confidence interval, 0.47-1.89; P=0.9). The risk for the
      primary bleeding outcome measure (moderate or severe bleeding by Global
      Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded
      Coronary Arteries classification) was lower in the CABG groups than in the PCI
      group (cumulative incidence: 1.3% versus 2.6%; unadjusted P=0.07; adjusted hazard
      ratio, 0.36; 95% confidence interval, 0.12-0.87; P=0.02). There were no
      interactions between the timing of surgery and the types of coronary
      revascularization (CABG/PCI) for both ischemic and bleeding outcomes.
      CONCLUSIONS: Surgical procedures were performed significantly more frequently
      after CABG than after PCI, particularly <6 months after coronary
      revascularization. Surgical procedures after CABG as compared with those after
      PCI were associated with similar risk for ischemic events and lower risk for
      bleeding events, regardless of the timing after coronary revascularization.

PMID- 25074254
TI  - Halofuginone stimulates adaptive remodeling and preserves re-endothelialization
      in balloon-injured rat carotid arteries.
AB  - BACKGROUND: Three major processes, constrictive vessel remodeling, intimal
      hyperplasia (IH), and retarded re-endothelialization, contribute to restenosis
      after vascular reconstructions. Clinically used drugs inhibit IH but delay re
      endothelialization and also cause constrictive remodeling. Here we have examined
      halofuginone, an herbal derivative, for its beneficial effects on vessel
      remodeling and differential inhibition of IH versus re-endothelialization.
      METHODS AND RESULTS: Two weeks after perivascular application to balloon-injured
      rat common carotid arteries, halofuginone versus vehicle (n=6 animals) enlarged
      luminal area 2.14-fold by increasing vessel size (adaptive remodeling; 123%),
      reducing IH (74.3%) without inhibiting re-endothelialization. Consistent with its
      positive effect on vessel expansion, halofuginone reduced collagen type 1 (but
      not type 3) production in injured arteries as well as that from adventitial
      fibroblasts in vitro. In support of its differential effects on IH versus re
      endothelialization, halofuginone produced greater inhibition of vascular smooth
      muscle cell versus endothelial cell proliferation at concentrations ~50 nmol/L.
      Furthermore, halofuginone at 50 nmol/L effectively blocked Smad3 phosphorylation
      in smooth muscle cells, which is known to promote smooth muscle cell
      proliferation, migration, and IH, but halofuginone had no effect on phospho-Smad3
      in endothelial cells. CONCLUSIONS: Periadventitial delivery of halofuginone
      dramatically increased lumen patency via adaptive remodeling and selective
      inhibition of IH without affecting endothelium recovery. Halofuginone is the
      first reported small molecule that has favorable effects on all 3 major processes
      involved in restenosis.

PMID- 25074256
TI  - Recruiting general practitioners as participants for qualitative and experimental
      primary care studies in Australia.
AB  - Recruiting general practitioners (GPs) for participation in primary care research
      is vitally important, but it can be very difficult for researchers to engage time
      poor GPs. This paper describes six different strategies used by a research team
      recruiting Australian GPs for three qualitative interview studies and one
      experimental study, and reports the response rates and costs incurred. Strategies
      included: (1) mailed invitations via Divisions of General Practice; (2)
      electronic newsletters; (3) combining mailed invitations and newsletter; (4) in
      person recruitment at GP conferences; (5) conference satchel inserts; and (6)
      combining in-person recruitment and satchel inserts. Response rates ranged from 0
      (newsletter) to 30% (in-person recruitment). Recruitment costs perparticipant
      ranged from A$83 (in-person recruitment) to A$232 (satchel inserts). Mailed
      invitations can be viable for qualitative studies, especially when free/low-cost
      mailing lists are used, if the response rate is less important. In-person
      recruitment at GP conferences can be effective for short quantitative studies,
      where a higher response rate is important. Newsletters and conference satchel
      inserts were expensive and ineffective.

PMID- 25074255
TI  - Fully integrated high-speed intravascular optical coherence tomography/near
      infrared fluorescence structural/molecular imaging in vivo using a clinically
      available near-infrared fluorescence-emitting indocyanine green to detect
      inflamed lipid-rich atheromata in coronary-sized vessels.
AB  - BACKGROUND: Lipid-rich inflamed coronary plaques are prone to rupture. The
      purpose of this study was to assess lipid-rich inflamed plaques in vivo using
      fully integrated high-speed optical coherence tomography (OCT)/near-infrared
      fluorescence (NIRF) molecular imaging with a Food and Drug Administration
      approved indocyanine green (ICG). METHODS AND RESULTS: An integrated high-speed
      intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were
      constructed based on a clinical OCT platform. For imaging lipid-rich inflamed
      plaques, the Food and Drug Administration-approved NIRF-emitting ICG (2.25 mg/kg)
      or saline was injected intravenously into rabbit models with experimental
      atheromata induced by balloon injury and 12- to 14-week high-cholesterol diets.
      Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta
      and iliac arteries was acquired only under contrast flushing through catheter
      (pullback speed up to <=20 mm/s). NIRF signals were strongly detected in the OCT
      visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to
      background ratio was significantly larger in the ICG-injected rabbits than in the
      saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background
      ratios were significantly higher in ICG-injected rabbits than in controls
      (P<0.01) on fluorescence reflectance imaging, which correlated well with the in
      vivo target-to-background ratios (P<0.01; r=0.85) without significant bias
      (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and
      histopathology also corroborated the in vivo imaging findings. CONCLUSIONS:
      Integrated OCT/NIRF structural/molecular imaging with a Food and Drug
      Administration -approved ICG accurately identified lipid-rich inflamed atheromata
      in coronary-sized vessels. This highly translatable dual-modal imaging approach
      could enhance our capabilities to detect high-risk coronary plaques.

PMID- 25074257
TI  - To biopsy or not to biopsy: evaluation of a large German cohort of patients with
      abnormal liver tests of unknown etiology.
AB  - BACKGROUND AND AIMS: Despite increasingly sensitive and accurate blood tests to
      detect liver disease, liver biopsy remains very useful in patients with atypical
      clinical features and abnormal liver tests of unknown etiology. The aim was to
      determine those elevated laboratory liver parameters that cause the clinician to
      order a biopsy, and whether laboratory tests are associated with pathological
      findings on histology. METHODS: 504 patients with unclear hepatopathy, admitted
      to the outpatient clinic of a university hospital between 2007 and 2010, were
      analyzed with respect to laboratory results, clinical data, and the results of
      liver biopsies. RESULTS: Aspartate aminotransferase (AST) and glutamate
      dehydrogenase (GLDH) levels above the normal range significantly increased the
      likelihood of recommending a liver biopsy by 81% [OR with 95% CI 1.81 (1.21
      2.71), p = 0.004] and 159% [OR with 95% CI 2.59 (1.70-3.93), p < 0.001],
      respectively. AST values above normal were associated with fibrosis (63 vs. 40%
      for normal AST, p = 0.010). Elevated ferritin levels pointed to a higher
      incidence of steatosis (48 vs. 10% for normal ferritin, p < 0.001) and
      inflammation (87 vs. 62% for normal ferritin, p = 0.004). CONCLUSIONS: Our
      results indicate that elevated AST and GLDH were associated with a greater
      likelihood of recommending liver biopsy. Elevated AST and ferritin levels were
      associated with steatosis, inflammation and fibrosis on liver biopsies. Thus, AST
      and ferritin may be useful non-invasive predictors of liver pathology in patients
      with unclear hepatopathy.

PMID- 25074258
TI  - Does it matter what we measure? Core outcomes, the IUJ and the CROWN and COMET
      initiatives.

PMID- 25074259
TI  - Comparison of location of mesh placed transvaginally vs mesh placed abdominally
      at the time of sacrocolpopexy.
AB  - INTRODUCTION AND HYPOTHESIS: The location of mesh placed at the time of abdominal
      sacrocolpopexy (ASC) is hypothesized to be in the same location histologically as
      mesh placed via full-thickness vaginal dissection in a cadaver model. METHODS:
      Ten fresh frozen cadavers underwent mesh placement via traditional ASC. In the
      same specimen, a transvaginal mesh (TVM) procedure was performed, attempting a
      full-thickness dissection. A block section was excised from each area including
      full thickness of the vagina and bladder with the intervening mesh. This was
      analyzed by a blinded pathologist. RESULTS: All cadavers underwent successful
      placement of both transabdominal mesh and TVM. Of the abdominally placed meshes,
      6 were located between the vagina and bladder, whereas 3 were situated within the
      vaginal wall, with an average depth of 0.30 mm. Five of the vaginal mesh pieces
      were placed between the bladder and vagina, and 4 within the vaginal wall at a
      depth of 0.25 mm. One specimen placed vaginally was 0.05 mm within the serosa of
      the bladder. One specimen could not be interpreted, despite multiple cuts.
      CONCLUSION: ASC and full-thickness vaginal dissection result in histologically
      similar locations. Dissection for ASC may only result in the correct plane
      between the bladder and vagina in approximately 60 % of cases. We achieved full
      thickness dissection for the transvaginal approach in 50 % of the cases, with one
      small penetration into the bladder serosa. Using a full-thickness dissection
      technique for TVM may be one way of reducing mesh exposure rates in those seen
      with ASC.

PMID- 25074260
TI  - InTone: a novel pelvic floor rehabilitation device for urinary incontinence.
AB  - INTRODUCTION: InTone(TM) (InControl Medical) is a nonimplanted vaginal device
      providing biofeedback and electrical stimulation of pelvic floor muscles. The
      purpose of this study was to assess its efficacy and usability for treating
      urinary incontinence (UI). METHODS: Women with UI (stress, urge, mixed) were
      recruited for this pilot trial. InTone was used 5-6 days a week for 12 weeks.
      Patients were assessed at baseline and monthly with symptom questionnaires
      [Urinary Distress Index (UDI6), Incontinence Impact Questionnaire (IIQ7)],
      bladder diaries. and 24-h pad-weight testing (PWT). Efficacy was assessed by
      comparing 12-week results to baseline values using chi-square and Wilcoxon rank
      sum tests. Usability was assessed with a device-usage log and the System
      Usability Scale (SUS), which evaluates patients' global impression of usability.
      RESULTS: Thirty-three women were enrolled; five patients withdrew and were
      excluded. Median age was 50 years (range 35-69). After 12 weeks of InTone
      therapy, median UDI6 and IIQ7 scores improved from 50.0 to 29.2 (p < 0.001) and
      from 42.9 to 14.3 (p < 0.001), respectively. Statistically significant reductions
      in median PWT (35.5-4.6 g, p < 0.001), median daily pad use (4.0-2.0, p < 0.001),
      and median daily incontinence frequency (4.3-1.0, p < 0.001) were noted; 68 % of
      patients achieved a > 50 % reduction in daily pad usage and PWT. Device usability
      was good, with a median SUS of 86.3 and a median expected use of 107 % (33-140
      %). CONCLUSIONS: Twelve weeks of InTone usage resulted in significant objective
      and subjective reductions in UI. Device usability was very good.

PMID- 25074262
TI  - New synthesis of two-dimensional CdSe/CdS core@shell dot-in-hexagonal platelet
      nanoheterostructures with interesting optical properties.
AB  - A new strategy for the synthesis of fluorescent monodispersed 2-dimensional (2D)
      CdSe/CdS core/shell hexagonal platelet nanocrystals has been demonstrated.
      Because of the stronger affinity of the -NH2 group of oleylamine to the (0001Se)
      facet comprising three dangling bonds in CdSe seeds, oleylamine acts as the sole
      surfactant responsible for hindering the growth of the CdS shell in the 0001 and
      0001[combining macron] facets and for helping the shell growth anisotropically in
      the <100> direction. The as-synthesized products were thoroughly characterized
      using XRD, TEM/HRTEM, HAADF and STEM for determining the crystal structure,
      growth mechanism and the position of the seed inside a core/shell nanocrystal.
      Optical absorption, PL, PLE and TRPL studies revealed efficient photoexcitation
      and the possibility of polarized emission from 2D core/shell nanocrystals. 

PMID- 25074264
TI  - Acute pulmonary embolus: the next frontier in venous thromboembolic
      interventions.
AB  - OPINION STATEMENT: Submassive pulmonary embolism (PE) represents a patient
      population that is under-recognized and under-treated. Recent clinical trials
      demonstrated the hemodynamic benefit of IV thrombolytic therapy among these
      patients; however, it came at the cost of a significantly increased risk of
      major, particularly intracranial, hemorrhage. Catheter-based treatment modalities
      have garnered considerable clinical interest in recent years. In particular,
      ultrasound accelerated thrombolysis, a catheter-based technology that enhances
      the process of thrombolytic delivery into the thrombus, has emerged as a
      treatment modality with an increasing number of single-center studies, as well as
      randomized, controlled clinical trials. Results from these experiences are
      consistent in achieving outcomes of thrombus resolution and hemodynamic recovery
      with a low dose thrombolytic infusion protocol, but without the high risk of
      bleeding complications associated with IV thrombolysis. The clinical data will
      hopefully be impactful to the development of the next edition of the treatment
      guidelines, in support of overall recommendations for catheter-based
      interventions. When available and with appropriate expertise, this modality
      should be considered as the preferred treatment of both massive and submassive
      PE.

PMID- 25074263
TI  - Pluripotent stem cells as a platform for cardiac arrhythmia drug screening.
AB  - OPINION STATEMENT: Since the first demonstrations of the differentiation of
      pluripotent stem cells to produce functional human cellular models such as
      cardiomyocytes, the scientific community has been captivated [1, 2**, 3]. In the
      time since that seminal work, the field has been catapulted forward by the
      demonstration that adult somatic cells can be reprogrammed to an induced state of
      pluripotency [4**], and more recently by the development of efficient and
      sophisticated genome editing tools [5**, 6**, 7], which together afford a
      theoretically unlimited supply of relevant genetic disease models. In particular,
      many of the early successes with induced pluripotent stem cell technology have
      been realized with cardiac arrhythmia syndromes [8**, 9-15]. There is interest in
      applying stem cell models in large-scale screens to discover novel therapeutics
      or drug toxicities. This manuscript aims to discuss the potential role of hPSC
      derived cardiomyocyte models in therapeutic arrhythmia screens and review recent
      advances in the field that bring us closer to this reality.

PMID- 25074265
TI  - Replacement of short segments within transmembrane domains of MC2R disrupts
      retention signal.
AB  - The proteolysis of the pro-opiomelanocortin precursor results in the formation of
      melanocortins (MCs), a group of peptides that share the conserved -H-F-R-W-
      sequence, which acts as a pharmacophore for five subtypes of MC receptors (MCRs).
      MC type 2 receptor (MC2R; also known as ACTHR) is the most specialized of all the
      MCRs. It is predominantly expressed in the adrenal cortex and specifically binds
      ACTH. Unlike other MCRs, it requires melanocortin receptor accessory protein 1
      (MRAP) for formation of active receptor and for its transport to the cell
      membrane. The molecular mechanisms underlying this specificity remain poorly
      understood. In this study, we used directed mutagenesis to investigate the role
      of various short MC2R sequence segments in receptor membrane trafficking and
      specific activation upon stimulation with ligands. The strategy of the study was
      to replace two to five amino acid residues within one MC2R segment with the
      corresponding residues of MC4R. In total, 20 recombinant receptors C-terminally
      fused to enhanced green fluorescent protein were generated and their membrane
      trafficking efficiencies and cAMP response upon stimulation with alpha-MSH and
      ACTH(1-24) were estimated during their stand-alone expression and coexpression
      with MRAP. Our results indicate that both the motif that determines the ligand
      recognition specificity and the intracellular retention signal are formed by a
      specific extracellular structure, which is supported by the correct alignment of
      the transmembrane domains. Our results also indicate that the aromatic-residue
      rich segment of the second extracellular loop is involved in the effects mediated
      by the second ACTH pharmacophore (-K-K-R-R-). 

PMID- 25074266
TI  - Minimal requirements for ubiquitination-mediated regulation of thyroid hormone
      activation.
AB  - Activation of thyroxine by outer ring deiodination is the crucial first step of
      thyroid hormone action. Substrate-induced ubiquitination of type 2 deiodinase
      (D2) is the most rapid and sensitive mechanism known to regulate thyroid hormone
      activation. While the molecular machinery responsible for D2 ubiquitination has
      been extensively studied, the combination of molecular features sufficient and
      required to allow D2 ubiquitination have not previously been determined. To
      address this question, we constructed chimeric deiodinases by introducing
      different combinations of D2-specific elements into type 1 deiodinase (D1),
      another member of the deiodinase enzyme family, which, however, does not undergo
      ubiquitination in its native form. Studies on the chimeric proteins expressed
      transiently in HEK-293T cells revealed that combined insertion of the D2-specific
      instability loop and the K237/K244 D2 ubiquitin carrier lysines into the
      corresponding positions of D1 could not ubiquitinate D1 unless the chimera was
      directed to the endoplasmic reticulum (ER). Fluorescence resonance energy
      transfer measurements demonstrated that the C-terminal globular domain of the ER
      directed chimera was able to interact with the E3 ligase subunit WSB1. However,
      this interaction did not occur between the chimera and the TEB4 (MARCH6) E3
      ligase, although a native D2 could readily interact with the N-terminus of TEB4.
      In conclusion, insertion of the instability loop and ubiquitin carrier lysines in
      combination with direction to the ER are sufficient and required to govern WSB1
      mediated ubiquitination of an activating deiodinase enzyme. 

PMID- 25074267
TI  - Regulation of CD163 mRNA and soluble CD163 protein in human adipose tissue in
      vitro.
AB  - CD163-positive macrophages are highly expressed in the human adipose tissue (AT)
      particularly from obese individuals. However, little is known about the
      regulation of CD163 mRNA and the protein level of sCD163 in human AT. We aimed to
      examine the regulation of CD163 and sCD163 in AT. Human s.c. AT samples (n=5)
      were stimulated with dexamethasone (DEX; 200  nmol/l), lipopolysaccharide (LPS;
      100  ng/ml), or DEX+LPS for various time periods up to 24  h. Gene expressions of
      CD163, ADAM17, IL10, and TNFA (TNF) were measured by RT-PCR. Protein levels of
      sCD163, IL10, and TNFalpha (TNF) were measured by ELISA. Furthermore, AT was
      separated into stromal and adipocyte fraction. We found that CD163 mRNA was
      strongly expressed in the stromal vascular fraction but hardly detectable in the
      isolated adipocytes. Incubating whole AT with DEX significantly up-regulated
      CD163 (P<0.001), whereas incubation with LPS had no effects on CD163 (P>0.05). By
      contrast, the protein level of sCD163 was not affected by DEX (P>0.05), but LPS
      significantly increased the level of sCD163 and TNFalpha (P<0.05). This might be
      due to the concomitant LPS stimulation of ADAM17, which is known to mediate
      shedding of the extracellular domains of sCD163 and TNFalpha. Finally, DEX
      significantly reduced the LPS-induced TNFalpha release to the incubation medium
      but had no effects on sCD163. We conclude that the expression of CD163 and the
      release of sCD163 are differentially regulated in human AT. Moreover, similar to
      studies on differentiated blood monocytes, TNFalpha and sCD163 are concomitantly
      released in human AT by LPS, which also up-regulate ADAM17.

PMID- 25074268
TI  - Fluticasone furoate/vilanterol: a review of its use in chronic obstructive
      pulmonary disease.
AB  - Fluticasone furoate/vilanterol (Relvar((r)), Breo((r)), Revinty((r))) is a fixed
      combination of a corticosteroid and a long-acting beta2-adrenergic agonist (LABA)
      for once-daily use via a dry powder inhaler (Ellipta((r))). Fluticasone
      furoate/vilanterol 100/25 ug is approved for the treatment of chronic obstructive
      pulmonary disease (COPD) in several countries. This article reviews the clinical
      use of the combination in COPD and summarises pharmacological properties.
      Fluticasone furoate has enhanced affinity for the glucocorticoid receptor
      compared with other clinically used inhaled corticosteroids (ICS) and longer lung
      retention than fluticasone propionate. Vilanterol is highly selective for beta2
      adrenoreceptors and provides a rapid and prolonged duration of action. In phase 3
      trials in patients with moderate to very severe COPD, overall, once-daily
      fluticasone furoate/vilanterol 100/25 ug improved pulmonary function more than
      placebo and fluticasone furoate alone and improved exacerbation rates more than
      vilanterol alone. With regard to pulmonary function, once-daily fluticasone
      furoate/vilanterol 100/25 MUg was more effective than twice-daily fluticasone
      propionate/salmeterol 250/50 ug and similarly effective as twice-daily
      fluticasone propionate/salmeterol 500/50 MUg. In 12-month trials, fluticasone
      furoate/vilanterol was generally well tolerated, and in 12- and 24-week trials,
      the incidence of adverse events was similar overall to that associated with the
      individual components or fluticasone propionate/salmeterol. However, as with the
      long-term use of all ICS agents, 12-month data indicate an increase in the risk
      of pneumonia with fluticasone furoate/vilanterol. In conclusion, fluticasone
      furoate/vilanterol is an effective and generally well tolerated additional
      LABA/ICS agent for the treatment of COPD with the added convenience of once-daily
      administration, which may improve treatment adherence in some patients. 

PMID- 25074269
TI  - HOMED-homicides eastern Denmark: an introduction to a forensic medical homicide
      database.
AB  - BACKGROUND: An introduction to a forensic medical homicide database established
      at the Department of Forensic Medicine in Copenhagen. CONTENT: The database
      contains substantial clinical and demographic data obtained in conjunction with
      medico-legal autopsies of victims and forensic clinical examinations of
      perpetrators in homicide cases in eastern Denmark. VALIDITY AND COVERAGE: The
      database contains information on all homicide cases investigated at the
      Department of Forensic Medicine in Copenhagen since 1971. Coverage for the
      catchment area of the department is assumed to be very good because of a medico
      legal homicide autopsy rate close to 100%. Regional differences might exist
      however, due to the fact that the catchment area of the department is dominated
      by the city of Copenhagen. CONCLUSIONS: The strength of the database includes a
      long running time, near complete regional coverage and an exhaustive list of
      registered variables it is useful for research purposes, although specific data
      limitations apply.

PMID- 25074270
TI  - Intersectoral action for health: the experience of a Danish municipality.
AB  - BACKGROUND: The aim was to build up evidence on intersectoral action for health
      at local government level by identifying both challenges and facilitating factors
      in collaboration between sectors when developing and implementing an
      intersectoral health policy in Varde, Denmark. METHODS: The study was carried out
      in 2011 using the case-study method. Approximately 500 pages of documents from
      the period 2007-2011 were analysed, and semi-structured interviews were carried
      out with nine key informants. RESULTS: The following challenges were identified:
      the policy was perceived as an additional task by employees outside the health
      sector; initially no direct funding was allocated to intersectoral projects; the
      level of ambition was not balanced between sectors; there was a lack of ownership
      of the policy; baseline measures were lacking and the policy had no clear
      objectives. Facilitating factors were considered to be: significant political
      support; public involvement; use of local media; establishment of a 'Fund for
      Health'; establishment of 'Health Networks' within sectors; and collaboration
      with a research group. CONCLUSIONS: Important practical lessons can be drawn from
      this experience for other cities planning to introduce similar formal
      intersectoral health policies in order to increase the chance of successful
      intersectoral action in further development and implementation of the
      intersectoral health policy in varde in the future, the challenges and
      facilitating factors identified in this study should be considered more evidence
      is required on the long-term health impacts of such policies.

PMID- 25074271
TI  - [Herniation in Supreme(r) (new cuff) laryngeal mask].

PMID- 25074272
TI  - Genetic structure and inter-generic relationship of closed colony of laboratory
      rodents based on RAPD markers.
AB  - Molecular genetic analysis was performed using random amplified polymorphic DNA
      (RAPD) on three commonly used laboratory bred rodent genera viz. mouse (Mus
      musculus), rat (Rattus norvegicus) and guinea pig (Cavia porcellus) as sampled
      from the breeding colony maintained at the Animal Facility, CSIR-Indian Institute
      of Toxicology Research, Lucknow. In this study, 60 samples, 20 from each genus,
      were analyzed for evaluation of genetic structure of rodent stocks based on
      polymorphic bands using RAPD markers. Thirty five random primers were assessed
      for RAPD analysis. Out of 35, only 20 primers generated a total of 56.88%
      polymorphic bands among mice, rats and guinea pigs. The results revealed
      significantly variant and distinct fingerprint patterns specific to each of the
      genus. Within-genera analysis, the highest (89.0%) amount of genetic homogeneity
      was observed in mice samples and the least (79.3%) were observed in guinea pig
      samples. The amount of genetic homogeneity was observed very high within all
      genera. The average genetic diversity index observed was low (0.045) for mice and
      high (0.094) for guinea pigs. The inter-generic distances were maximum (0.8775)
      between mice and guinea pigs; and the minimum (0.5143) between rats and mice. The
      study proved that the RAPD markers are useful as genetic markers for assessment
      of genetic structure as well as inter-generic variability assessments.

PMID- 25074274
TI  - Identification and characterization of ace2-type acetylcholinesterase in
      insecticide-resistant and -susceptible parasitoid wasp Oomyzus sokolowskii
      (Hymenoptera: Eulophidae).
AB  - A full-length acetylcholinesterase (AChE) cDNA sequence (Os-ace2.s) from
      insecticide-susceptible (S) parasitoid Oomyzus sokolowskii (Hymenoptera:
      Eulophidae) and a partial cDNA sequence (Os-ace2.r) from insecticide- resistant
      (R) O. sokolowskii were identified firstly. Both Os-ace2.s (encoding a protein of
      639 amino acid residues) and Os-ace2.r (encoding a protein of 530 amino acid
      residues) contained the typical conserved motifs, including FGESAGdomains,
      catalytic triad, acyl pocket, three oxy-anino hole, choline binding site,
      peripheral anionic site, omega loop and conserved aromatic residues. The multiple
      alignment and Blast results indicated that Os-ace2.s were ace2 member of AChE
      gene. There were three replacements of the amino acid residues (Glu 115 Leu, Phe
      394 Leu, and Lys 424 Arg) between Os-ace2.s and Os-ace2.r. The ace2 of O.
      sokolowskii was the AChE gene firstly isolated from hymenopteran parasitoid so
      far. R O. sokolowskii displayed about 15-20-folds resistance ratios to
      methamidophos and avermectin. The bimolecular rate constant (k i) value in S O.
      sokolowskii was 3.8-folds for methamidophos and 12.3 for dichlorvos, respectively
      higher than those in R O. sokolowskii. The results indicated that the insensitive
      AChE and replacements of the amino acid residues in Os-ace2 might be involved in
      the resistance to methamidophos in R O. sokolowskii. 

PMID- 25074273
TI  - Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene.
AB  - The aim of this study is to investigate the genetic influence of polymorphisms in
      fat mass and obesity associated (FTO) gene on a sample of obese subjects and
      controls. Obesity is an epidemic all over the world. Several polymorphisms in the
      first intron of FTO gene have been associated with common forms of human obesity.
      In this research rs1421085 and rs9939609 polymorphisms of FTO gene were genotyped
      in 190 obese patients with a BMI >=30 kg/m(2) (Body Mass Index) and 97 healthy
      controls with a BMI of 18.5-24.9. Genotyping of SNPs was performed by real-time
      polymerase chain reaction. Body composition was established with bioelectric
      impedance analysis. Waist-to-hip ratio was determined for all participants. There
      were no significant differences (P > 0.05) between obese cases and controls in
      terms of genotype frequencies of rs1421085 and rs9939609 polymorphisms in our
      study. Also there were no significant correlations between genotypes and obesity
      related (anthropometric-body composition) parameters (P > 0.05). 

PMID- 25074276
TI  - The volume-outcome relationship in colorectal surgery.

PMID- 25074277
TI  - From regional pulse vaccination to global disease eradication: insights from a
      mathematical model of poliomyelitis.
AB  - Mass-vaccination campaigns are an important strategy in the global fight against
      poliomyelitis and measles. The large-scale logistics required for these mass
      immunisation campaigns magnifies the need for research into the effectiveness and
      optimal deployment of pulse vaccination. In order to better understand this
      control strategy, we propose a mathematical model accounting for the disease
      dynamics in connected regions, incorporating seasonality, environmental
      reservoirs and independent periodic pulse vaccination schedules in each region.
      The effective reproduction number, Re, is defined and proved to be a global
      threshold for persistence of the disease. Analytical and numerical calculations
      show the importance of synchronising the pulse vaccinations in connected regions
      and the timing of the pulses with respect to the pathogen circulation
      seasonality. Our results indicate that it may be crucial for mass-vaccination
      programs, such as national immunisation days, to be synchronised across different
      regions. In addition, simulations show that a migration imbalance can increase Re
      and alter how pulse vaccination should be optimally distributed among the
      patches, similar to results found with constant-rate vaccination. Furthermore,
      contrary to the case of constant-rate vaccination, the fraction of environmental
      transmission affects the value of Re when pulse vaccination is present.

PMID- 25074279
TI  - Using an epidemiological model to investigate unwarranted variation: the case of
      ventilation tubes for otitis media with effusion in England.
AB  - OBJECTIVES: To investigate unwarranted variation in ventilation tube insertions
      for otitis media with effusion in children in England. This procedure is known to
      be 'overused' from clinical audits, as only one in three ventilation tube
      insertions conforms to the appropriateness criteria of the National Institute for
      Health and Care Excellence (NICE); but audits cannot identify the scale of
      'underuse' - i.e. patients who would benefit but are not treated. METHODS: To
      explore both 'underuse' and 'overuse' of ventilation tubes for otitis media with
      effusion, we developed an epidemiological model based on: definitions of children
      with otitis media with effusion expected to benefit from ventilation tubes
      according to NICE guidance; epidemiological and clinical information from a
      systematic review; and expert judgement. A range of estimates was derived using
      Monte Carlo simulation and compared with the number of ventilation tubes provided
      in the English National Health Service in 2010. RESULTS: About 32,200 children in
      England would be expected to benefit from ventilation tubes for otitis media with
      effusion per year (between 20,411 and 45,231 with 90% certainty). The observed
      number of ventilation tubes for otitis media with effusion-associated diagnoses
      was 16,824. CONCLUSIONS: The expected population capacity to benefit from
      ventilation tubes for otitis media with effusion based on NICE guidance appeared
      to exceed, by far, the number of ventilation tubes provided in the English
      National Health Service. So, while there is known 'overuse', there also may be
      substantial 'underuse' of ventilation tubes for otitis media with effusion if
      NICE criteria were applied. Future investigations of unwarranted variation
      should, therefore, not only focus on the patients who are treated but also
      consider the potential for benefit at the population level.

PMID- 25074280
TI  - Advances in clinical cardiology.
AB  - Multiple, potentially practice-changing cardiology trials have been presented or
      published over the past year. In this paper, we summarize and place in clinical
      context, new data regarding management of acute coronary syndrome and ST
      elevation myocardial infarction (copeptin assessment, otamixaban, cangrelor,
      prasugrel, sodium nitrite, inclacumab, ranolazine, preventive coronary
      intervention of non-culprit lesions, immediate thrombolytic therapy versus
      transfer for primary intervention), new coronary intervention data (thrombectomy,
      radial access, pressure wire fractional flow reserve, antiplatelet therapy
      duration and gene-guidance, permanent and biodegradable polymers, coronary
      bifurcation and strategies), and coronary artery bypass data (off pump vs. on
      pump). Latest trials in trans-aortic valve implantation, heart failure
      (eplerenone, aliskiren, spironolactone, sildenafil, dopamine, nesiritide,
      omecamtiv mecarbil, the algisyl left ventricular augmentation device, and echo
      guided cardiac resynchronization), atrial fibrillation (edoxaban, dabigatran, and
      ablation), cardiac arrest (hypothermia, LUCASTM mechanical chest compression),
      and cardiovascular prevention (vitamins, renal denervation for resistant
      hypertension, renal artery stenting, saxagliptin, alogliptin, and gastric
      banding) are also discussed. 

PMID- 25074278
TI  - How the proteome packages the genome for cardiovascular development.
AB  - The devastating impact of congenital heart defects has made mechanisms of
      vertebrate heart and vascular development an active area of study. Because
      myocyte death is a common feature of acquired cardiovascular diseases and the
      adult heart does not regenerate, the need exists to understand whether features
      of the developing heart and vasculature-which are more plastic-can be exploited
      therapeutically in the disease setting. We know that a core network of
      transcription factors governs commitment to the cardiovascular lineage, and
      recent studies using genetic loss-of-function approaches and unbiased genomic
      studies have revealed the role for various chromatin modulatory events. We reason
      that chromatin structure itself is a causal feature that influences transcriptome
      complexity along a developmental continuum, and the purpose of this article is to
      highlight the areas in which 'omics technologies have the potential to reveal new
      principles of phenotypic plasticity in development. We review the major
      mechanisms of chromatin structural regulation, highlighting what is known about
      their actions to control cardiovascular differentiation. We discuss emergent
      mechanisms of regulation that have been identified on the basis of genomic and
      proteomic studies of cardiac nuclei and identify current challenges to an
      integrated understanding of chromatin structure and cardiovascular phenotype.

PMID- 25074281
TI  - Spleen stiffness can non-invasively assess resolution of portal hypertension
      after liver transplantation.
AB  - BACKGROUND & AIMS: Spleen stiffness can be measured by transient elastography.
      Recent studies have shown that spleen stiffness correlates with hepatic venous
      pressure gradient and can predict oesophageal varices. Elevated spleen stiffness
      in cirrhosis has been attributed to splenic tissue hyperplasia and fibrosis,
      portal hypertension and its consequent hyperdynamic circulation. The aim of this
      study was to investigate changes to spleen stiffness after orthotopic liver
      transplantation (OLT) when portal hypertension resolves. METHODS: Twenty-one
      patients awaiting OLT were studied prospectively, while 11 post-transplant
      patients were recruited as controls. Spleen and liver stiffness were measured
      with Fibroscan before and at 2-8 weeks after OLT. Criteria applied for spleen
      stiffness measurement were similar to liver stiffness (>=10 measurements; >=60%
      success rate; interquartile range, IQR <30% of median). RESULTS: Spleen stiffness
      was significantly higher before OLT compared to post-transplant patients [75.0
      (63.9-75.0) kPa vs. 28.4 (22.0-37.5) kPa; P < 0.0001]. For patients awaiting OLT,
      90% (19/21) had oesophageal varices (endoscopically or radiologically). In
      patients who underwent liver transplantation, spleen stiffness decreased
      significantly from a median of 75.0 (62.0-75.0) kPa before OLT, to 41.9 (27.0
      47.4) kPa at 2 weeks after transplant and 32.9 (29.1-38.0) kPa in the subsequent
      4-8 weeks after OLT (P < 0.0001). As expected, liver stiffness measurements
      reduced from 39.3 (24.9-75.0) kPa to 8.6 (6.8-11.8) kPa in patients receiving OLT
      (P = 0.0004). CONCLUSIONS: Spleen stiffness can non-invasively assess changes in
      portal pressure after liver transplantation and decreases significantly when
      portal hypertension resolves.

PMID- 25074282
TI  - High-frequency ultrasound findings in gonococcal inflammation of the paraurethral
      glands in men.

PMID- 25074284
TI  - Comparison of human metapneumovirus, respiratory syncytial virus and Rhinovirus
      respiratory tract infections in young children admitted to hospital.
AB  - Respiratory Syncytial Virus (RSV), Human metapneumovirus (HMPV), and Rhinoviruses
      (RV) are frequent causes of respiratory tract infections in young children. We
      compared laboratory and clinical findings in children with comparable age
      distribution and hospitalized due to RSV, HMPV or RV infections. Viral pathogens
      were detected by a quantitative real time PCR from nasopharyngeal aspirates. No
      significant differences in the admission diagnosis, laboratory parameters,
      patient demographics and treatment measures between the three viral causes of
      respiratory illness were found. No correlation between viral load and disease
      severity was observed however, there was a significantly lower concentration of
      the nasopharyngeal interleukin 8 (IL-8) in children with RV compared to HMPV and
      RSV, indicating a milder proinflammatory reaction. Moreover, RV-infected children
      had significantly lower body temperature, higher leucocyte counts in peripheral
      blood, and a tendency to have a shorter stay in hospital than children with
      either HMPV or RSV infection. Taken together, clinical presentation of the
      infections with RSV, HMPV, and RV is similar among children of the same age group
      and not clearly distinguishable by standard clinical or laboratory findings.
      Therefore, virus specific testing should be included regularly for routine
      diagnosis of children with respiratory tract infections.

PMID- 25074283
TI  - The effect of various cold-water immersion protocols on exercise-induced
      inflammatory response and functional recovery from high-intensity sprint
      exercise.
AB  - PURPOSE: The purpose of this study was to investigate the effects of different
      cold-water immersion (CWI) protocols on the inflammatory response to and
      functional recovery from high-intensity exercise. METHODS: Eight healthy
      recreationally active males completed five trials of a high-intensity
      intermittent sprint protocol followed by a randomly assigned recovery condition:
      1 of 4 CWI protocols (CWI-10 min * 20  degrees C, CWI-30 min * 20  degrees C, CWI
      10 min * 10  degrees C, or CWI-30 min * 10  degrees C) versus passive rest.
      Circulating mediators of the inflammatory response were measured from EDTA plasma
      taken pre-exercise (baseline), immediately post-exercise, and at 2, 24, and 48 h
      post-exercise. Ratings of perceived soreness and impairment were noted on a 10-pt
      Likert scale, and squat jump and drop jump were performed at these time points.
      RESULTS: IL-6, IL-8, and MPO increased significantly from baseline immediately
      post-exercise in all conditions. IL-6 remained elevated from baseline at 2 h in
      the CWI-30 min * 20  degrees C, CWI-10 min * 10  degrees C, and CWI-30 min * 10 
      degrees C conditions, while further increases were observed for IL-8 and MPO in
      the CWI-30 min * 20  degrees C and CWI-30 min * 10  degrees C conditions. Squat
      jump and drop jump height were significantly lower in all conditions immediately
      post-exercise and at 2 h. Drop jump remained below baseline at 24 and 48 h in the
      CON and CWI-10 min * 20  degrees C conditions only, while squat jump height
      returned to baseline in all conditions. CONCLUSIONS: Cold-water immersion appears
      to facilitate restoration of muscle performance in a stretch-shortening cycle,
      but not concentric power. These changes do not appear to be related to
      inflammatory modulation. CWI protocols of excessive duration may actually
      exacerbate the concentration of cytokines in circulation post-exercise; however,
      the origin of the circulating cytokines is not necessarily skeletal muscle.

PMID- 25074285
TI  - Fluconazole pharmacokinetics in a morbidly obese, critically ill patient
      receiving continuous venovenous hemofiltration.
AB  - Current fluconazole dosing strategies can be described using either standardized
      doses (800 or 400 mg) or as weight-based dosing recommendations (12 mg/kg loading
      dose followed by 6 mg/kg maintenance dose). The ideal method of fluconazole
      dosing is still unclear for certain patient populations, such as those receiving
      renal replacement therapy or the morbidly obese. We describe a 48-year-old man
      with a body mass index of 84 kg/m(2) who was receiving continuous venovenous
      hemofiltration (CVVH) and was treated with fluconazole by using a weight-based
      dose determined by lean body weight, infused at a rate of 200 mg/hour. Blood
      samples were collected at hour 0 (i.e., ~24 hrs after the loading dose was
      administered) and at 3.5, 6.8, and 11.3 hours after the start of the 600-mg
      maintenance dose, infused over 3 hours. Pharmacokinetic parameters calculated
      were maximum serum concentration 9.64 mg/L, minimum serum concentration 5.98
      mg/L, area under the serum concentration-time curve from 0-24 hours (AUC0-24 )
      184.75 mg/L*hour, elimination rate constant 0.0199 hour(-1) , elimination half
      life 34.8 hours, and total body clearance 3.25 L/hour. Our data, when combined
      with previously published literature, do not support using a linear dose-to-AUC
      approximation to estimate drug dosing needs in the critically ill patient
      population receiving CVVH. In addition, our results suggest that morbidly obese
      patients are able to achieve pharmacodynamic goals defined as an AUC:MIC ratio
      higher than 25 by using a lean body weight for fluconazole dosing calculations.

PMID- 25074286
TI  - New insights into the functions of PIGF, a protein involved in the ethanolamine
      phosphate transfer steps of glycosylphosphatidylinositol biosynthesis.
AB  - PIGF is a protein involved in the ethanolamine phosphate (EtNP) transfer steps of
      glycosylphosphatidylinositol (GPI) biosynthesis. PIGF forms a heterodimer with
      either PIGG or PIGO, two enzymes that transfer an EtNP to the second or third
      mannoses of GPI respectively. Heterodimer formation is essential for stable and
      regulated expression of PIGO and PIGG, but the functional significance of PIGF
      remains obscure. In the present study, we show that PIGF binds to PIGO and PIGG
      through distinct molecular domains. Strikingly, C-terminal half of PIGF was
      sufficient for its binding to PIGO and PIGG and yet this truncation mutant could
      not complement the PIGF defective mutant cells, suggesting that heterodimer
      formation is not sufficient for PIGF function. Furthermore, we identified a
      highly conserved motif in PIGF and demonstrated that the motif is not involved in
      binding to PIGO or PIGG, but critical for its function. Finally, we identified a
      PIGF homologue from Trypanosoma brucei and showed that it binds specifically to
      the T. brucei PIGO homologue. These data together support the notion that PIGF
      plays a critical and evolutionary conserved role in the ethanolamine-phosphate
      transfer-step, which cannot be explained by its previously ascribed
      binding/stabilizing function. Potential roles of PIGF in GPI biosynthesis are
      discussed. 

PMID- 25074288
TI  - The dawn of chelonian research: turtles between comparative anatomy and
      embryology in the 19th century.
AB  - Many evo-devo studies of the turtle's shell draw hypotheses and support from
      historical sources. The groundbreaking works of Cuvier, Geoffroy St. Hilaire,
      Carus, Rathke, Owen, and others are being revived in modern research, and their
      centuries-old understanding of the turtle's shell reconsidered. In the works of
      these eminent biologists of the 19th century, comparative anatomy and embryology
      of turtle morphology set the stage for future studies in developmental biology,
      histology, and paleontology. Given the impact that these works still make on
      modern research, it is important to develop a thorough appreciation of previous
      authors, regarding how they arrived at their conclusions (i.e., what counted as
      evidence?), whether there was debate amongst these authors about shell
      development (i.e., what counted as an adequate explanation?), and even why these
      men, some of the most powerful and influential thinkers and anatomists of their
      day, were concerned with turtles. By tracing and exposing the context and content
      of turtle shell studies in history, our aim is to inform modern debates about the
      evolution and development of the turtle's shell.

PMID- 25074289
TI  - Context reinstatement and memory for intrinsic versus extrinsic context: the role
      of item generation at encoding or retrieval.
AB  - According to many theoretical accounts, reinstating study context at the time of
      test creates optimal circumstances for item retrieval. The role of context
      reinstatement was tested in reference to context memory in several experiments.
      On the encoding phase, participants were presented with words printed in two
      different font colors (intrinsic context) or two different sides of the computer
      screen (extrinsic context). At test, the context was reinstated or changed and
      participants were asked to recognize words and recollect their study context.
      Moreover, a read-generate manipulation was introduced at encoding and retrieval,
      which was intended to influence the relative salience of item and context
      information. The results showed that context reinstatement had no effect on
      memory for extrinsic context but affected memory for intrinsic context when the
      item was generated at encoding and read at test. These results supported the
      hypothesis that context information is reconstructed at retrieval only when
      context was poorly encoded at study. 

PMID- 25074290
TI  - Deriving and evaluating new accelerometer cut-points in young children - a
      comment on Johansson et al. (2014).

PMID- 25074291
TI  - Spruelike enteropathy related to olmesartan treatment.

PMID- 25074292
TI  - Sarcopenia research: Relevance of methodology.

PMID- 25074293
TI  - The effects of computed tomography image characteristics and knot spacing on the
      spatial accuracy of B-spline deformable image registration in the head and neck
      geometry.
AB  - OBJECTIVES: To explore the effects of computed tomography (CT) image
      characteristics and B-spline knot spacing (BKS) on the spatial accuracy of a B
      spline deformable image registration (DIR) in the head-and-neck geometry.
      METHODS: The effect of image feature content, image contrast, noise, and BKS on
      the spatial accuracy of a B-spline DIR was studied. Phantom images were created
      with varying feature content and varying contrast-to-noise ratio (CNR), and
      deformed using a known smooth B-spline deformation. Subsequently, the deformed
      images were repeatedly registered with the original images using different BKSs.
      The quality of the DIR was expressed as the mean residual displacement (MRD)
      between the known imposed deformation and the result of the B-spline DIR.Finally,
      for three patients, head-and-neck planning CT scans were deformed with a
      realistic deformation field derived from a rescan CT of the same patient,
      resulting in a simulated deformed image and an a-priori known deformation field.
      Hence, a B-spline DIR was performed between the simulated image and the planning
      CT at different BKSs. Similar to the phantom cases, the DIR accuracy was
      evaluated by means of MRD. RESULTS: In total, 162 phantom registrations were
      performed with varying CNR and BKSs. MRD-values < 1.0 mm were observed with a BKS
      between 10-20 mm for image contrast >= +/- 250 HU and noise < +/- 200 HU.
      Decreasing the image feature content resulted in increased MRD-values at all
      BKSs. Using BKS = 15 mm for the three clinical cases resulted in an average MRD <
      1.0 mm. CONCLUSIONS: For synthetically generated phantoms and three real CT cases
      the highest DIR accuracy was obtained for a BKS between 10-20 mm. The accuracy
      decreased with decreasing image feature content, decreasing image contrast, and
      higher noise levels. Our results indicate that DIR accuracy in clinical CT images
      (typical noise levels < +/- 100 HU) will not be effected by the amount of image
      noise.

PMID- 25074294
TI  - Severe morbidities associated with induced abortions among misoprostol users and
      non-users in a tertiary public hospital in Ghana.
AB  - BACKGROUND: Misoprostol has become a popular over the counter self-administered
      abortifacient in Ghana. This study aimed to compare the socio-demographic
      characteristics and clinical complications associated with misoprostol and non
      misoprostol induced abortions among patients admitted to a tertiary public health
      facility in Ghana. METHODS: This was a cross sectional study conducted at the
      gynaecological ward of Komfo Anokye Teaching Hospital (KATH), over a four-month
      period using a structured pre-tested questionnaire. Data were analysed using Chi
      square, Fisher's exact and student t-tests. Factors associated with severe
      morbidity were examined using Poisson regression with robust error variance to
      estimate crude and adjusted relative risks (RRs) with 95% confidence intervals
      (CIs). P < 0.05 was considered statistically significant. RESULTS: Overall, 126
      misoprostol users and 126 misoprostol non-users were recruited into the study.
      About 71% of the clients had self-induced abortions. Misoprostol users were more
      likely to be younger (p < 0.001), single (p < 0.001), nulliparous (p = 0.001), of
      higher educational background (p = 0.001), and unemployed (p < 0.001), than
      misoprostol non-users. Misoprostol users were more likely than non-users to
      undergo termination of pregnancy because they wanted to continue schooling (p <
      0.001) or were not earning regular income to support a family (p = 0.001).
      Overall, 182 (72.2%) of the women (79.4% misoprostol users vs. 65.1% misoprostol
      non-users; p = 0.01) suffered severe morbidity. Nulliparous women (adjusted RR,
      1.28; 95% CI, 1.08-1.52) and those who had induced abortion after 12 weeks'
      gestation (adjusted RR, 1.36; 95% CI, 1.18-1.57) were at increased risks of
      experiencing severe morbidity. The association between mode of abortion induction
      and severe morbidity was not statistically significant (p = 0.06). CONCLUSION:
      Self-induced abortions using misoprostol is a common practice among women in this
      study; nearly three quarters of them suffered severe morbidity. Nonetheless,
      severe morbidity among misoprostol users and non-users did not differ
      significantly but was directly related to the gestational age at which the
      induced abortions occurred. Health education on the dangers of self-induced
      abortions and appropriate use of medication abortion could help reduce
      complications associated with induced abortions in Ghana.

PMID- 25074295
TI  - External validation of European Organization for Research and Treatment of Cancer
      and Spanish Urological Club for Oncological Treatment scoring models to predict
      recurrence and progression in Japanese patients with non-muscle invasive bladder
      cancer treated with bacillus Calmette-Guerin.
AB  - OBJECTIVE: To validate two prediction models (European Organization for Research
      and Treatment of Cancer and Spanish Urological Club for Oncological Treatment)
      for recurrence and progression of non-muscle invasive bladder cancer in Japanese
      patients who underwent bacillus Calmette-Guerin instillation therapy. METHODS:
      From March 1985 to April 2007, data were analyzed from 366 patients who underwent
      transurethral resection of bladder tumor followed by bacillus Calmette-Guerin
      instillation therapy. The ability of two scoring models to predict recurrence and
      progression was assessed by concordance index. RESULTS: For recurrence
      probability, the concordance index of the European Organization for Research and
      Treatment of Cancer and Spanish Urological Club for Oncological Treatment models
      was 0.514 and 0.576, respectively, which was lower than that (0.604) of a
      selected single prognostic factor (age) by our multivariate analysis. For
      progression probability, the concordance index of European Organization for
      Research and Treatment of Cancer and Spanish Urological Club for Oncological
      Treatment models was 0.693 and 0.764, respectively, which was higher than that
      (0.633) of a selected single factor (T stage) by our multivariate analysis. The
      Spanish Urological Club for Oncological Treatment scoring system resulted in
      better stratification of tumor recurrence and progression when compared with the
      European Organization for Research and Treatment of Cancer model, probably
      because more patients underwent bacillus Calmette-Guerin treatment in the Spanish
      Urological Club for Oncological Treatment cohort than in the European
      Organization for Research and Treatment of Cancer cohort. CONCLUSIONS: The
      Spanish Urological Club for Oncological Treatment scoring system is a good
      predictor of tumor recurrence and progression in Japanese patients who underwent
      bacillus Calmette-Guerin immunotherapy. A large prospective study is warranted to
      confirm the efficacy of this system.

PMID- 25074297
TI  - Association between physical activity and substance use behaviors among high
      school students participating in the 2009 Youth Risk Behavior Survey.
AB  - This study examined the relationship between physical activity, physical
      education class, and sports participation on the substance use practices of
      adolescents. Data was derived from the 2009 Youth Risk Behavior Survey study of
      adolescent behaviors. The results of this study indicated that recreational
      physical activity, attending PE class, and participating in sports were
      independent protective factors for many cigarette use behaviors but not for
      smokeless tobacco use. Additionally, recreational physical activity and sports
      participation appears to be a protective factor for marijuana use among females
      but not males. On the other hand, recreational physical activity and sports
      participation appears to be a risk factor for alcohol use behaviors among males.

PMID- 25074296
TI  - Depressive rumination and past depression in Japanese university students:
      comparison of brooding and reflection.
AB  - The Ruminative Responses Scale, a measure of depressive rumination, contains two
      subscales: Brooding and Reflection. Treynor, Gonzalez, and Nolen-Hoeksema (2003)
      proposed that Brooding is maladaptive and Reflection is adaptive. This article
      examined the relationships among Brooding, Reflection, and previous depression in
      two samples of Japanese undergraduates, who were non-depressed at the time of
      their participation. Based on answers to a self-report measure, participants were
      divided into a formerly depressed group, who had experienced an episode that met
      the criteria for major depression, and a never-depressed group. Logistic
      regression analyses were conducted with Brooding, Reflection, and current
      depression as the independent variables and past depression as the dependent
      variable. Brooding had consistent positive associations with past depression. The
      relationship between Reflection and past depression was not significant for one
      sample, but was statistically significant and positive in the second sample. In
      the second sample, Brooding and Reflection both were related with past depression
      after controlling for worry.

PMID- 25074298
TI  - Employee problems and their consequences in the technology industry: evidence
      from surveys and counseling records.
AB  - To support employees' work and health, organizations should help employees cope
      with common problems. Previous studies have focused primarily on work-related
      problems across multiple industries rather than on evaluating industry-specific
      issues. Here, two approaches identified common work and non-work employee
      problems in the technology industry with the strongest correlations with
      psychosomatic health and life satisfaction. Study 1 used questionnaires to
      identify the problems that were perceived as the most frequent by lower-level
      employees (N = 355) working in the technology industry. Study 2 evaluated
      employees' coping behaviors by analyzing (with permission) counseling records
      collected from an employee assistance service company (N = 276). Employees
      reported a variety of problems; work problems were the only problems (of the top
      5 problems) reported in both studies. Several problems emerged in the counseling
      records (e.g., legal issues, career development, family and marriage problems,
      and emotional problems) but not in the surveys. Future research should apply
      these observations to develop scales for measuring employee stressors.

PMID- 25074299
TI  - The effect of amount and tangibility of endowment and certainty of recipients on
      selfishness in a modified dictator game.
AB  - Taiwanese college students (N = 101) participated in the study to examine the
      effects of the amount of an endowment, the tangibility of an endowment, and the
      certainty of the recipient on selfishness in a modified dictator game. Results
      showed that dictators were more selfish when allocating tangible (money) than
      less tangible (honor credits) endowments. Selfishness was higher when large
      amounts of money were involved. The certainty of the recipient was manipulated by
      whether the recipient was chosen and announced before or after the decision.
      Unexpectedly, participants were more self-interested in the certain-recipient
      condition than in the uncertain-recipient condition. In the honor condition, the
      amount of an endowment and the certainty of the recipient did not affect
      participants' allocations.

PMID- 25074300
TI  - Studies of transformational leadership: evaluating two alternative models of
      trust and satisfaction.
AB  - This study evaluates the influence of leadership style and employee trust in
      their leaders on job satisfaction. 341 personnel (164 men, 177 women; M age =
      33.5 yr., SD = 5.1) from four large insurance companies in Taiwan completed the
      transformational leadership behavior inventory, the leadership trust scale and a
      short version of the Minnesota (Job) Satisfaction Questionnaire. A bootstrapping
      mediation and structural equation modeling revealed that the effect of
      transformational leadership on job satisfaction was mediated by leadership trust.
      This study highlights the importance of leadership trust in leadership
      satisfaction relationships, and provides managers with practical ways to enhance
      job satisfaction.

PMID- 25074301
TI  - Supervisor security provision: correlates and related mechanisms.
AB  - Attachment security in relationships is associated with several positive
      outcomes. Recently, researchers have applied attachment theory to employee
      supervisor relationships. Two studies examined associations of supervisors'
      provision of attachment-related security with work-related outcomes and related
      underlying mechanisms. Participants completed measures of their supervisors'
      security provisions and of their own job satisfaction, organizational commitment,
      burnout, and performance. Supervisors' security provisions were associated with
      positive work-related outcomes, which were mediated by closeness behaviors (Study
      1; N = 150, M age = 33.3 yr., SD = 9.6). These associations were also mediated by
      employees' sense of meaning at work when the supervisor was of the same sex
      (Study 2; N = 120, M age = 26.5 yr., SD = 5.0). Findings supported attachment
      related dynamics in employee-supervisor relationships and suggested psychological
      mechanisms underlying these effects.

PMID- 25074302
TI  - Psychometric properties of an Italian version of the Experiences in Close
      Relationships-Revised (ECR-R) Scale.
AB  - This study examined the psychometric properties of a newly translated Italian
      version of the Experiences in Close Relationships-Revised (ECR-R) Scale. The
      sample comprised 1,363 adults (906 women, 456 men, 1 unreported sex; ages 18-64
      yr., M = 33.4, SD = 8.9; 84.4% reported being engaged in a romantic relationship,
      9.4% declared being single), all living in Italy and speaking Italian as their
      first language. Exploratory and confirmatory factor analyses showed the expected
      bi-factorial (anxiety/avoidance) structure and a close correspondence between
      factors and scales. Test-retest and internal consistency reliabilities were
      adequate. Correlations with the Relationship Questionnaire, a categorical measure
      of attachment, and with the Dyadic Adjustment Scale were consistent with the
      theoretical relations among the constructs. The findings confirm the
      transcultural validity of the ECR-R.

PMID- 25074303
TI  - Cognitive diagnostic assessment with different weight for attribute: based on the
      Dina model.
AB  - An attribute weight calculation method which used a Bayesian network and the
      least squares distance method was proposed to assign different weights to
      different attributes in cognitive diagnosis. This method is independent of any
      specific cognitive diagnostic models, so it is practicable to consider attribute
      weight not only in the models with explicit expression but also in item response
      theory-based cognitive diagnostic methods. Simulation studies showed that the
      data fit for the least squares distance method was excellent and the weighted
      status can yield higher correct classification rates than the unweighted status.
      The weighted status had a promising performance in recognizing the knowledge
      states of examinees for various slippage probabilities under different attribute
      hierarchies. The numbers of items and attributes could also affect the examinees'
      classification accuracy.

PMID- 25074304
TI  - Psychometric evaluation of the Chinese version of the Questionnaire on Teacher
      Interaction (C-QTI) in Hong Kong.
AB  - This study validated the Chinese version of the Questionnaire on Teacher
      Interaction (C-QTI) with two samples (ns = 370 and 369) of primary school
      students in Hong Kong. The 48-item measure had acceptable internal consistency
      reliability, but the reliability coefficients of four of the scales were too low.
      The findings supported the validity of the circumplex model underlying the
      instrument and verified the ability of the measure to differentiate between
      students' perceptions in different classes. With the refinement of the measure
      based on reliability analysis and Principal Components Analysis, Confirmatory
      Factor Analysis was conducted on the 35-item instrument to test its hypothesized
      factor structure. Findings on model fit indices were mixed, lending some support
      to the eight-factor structure of the questionnaire.

PMID- 25074305
TI  - Examining relationships between multiple health risk behaviors, well-being, and
      productivity.
AB  - Traditionally, the concept of health promotion has emphasized the reduction of
      health risk behaviors to reduce disease and impairment. Well-being research
      expands this focus to include positive constructs such as thriving, productivity,
      life-evaluation, and emotional and physical health. The objective of the present
      study was to examine the relationships between health risk behaviors and specific
      measures of individual well-being. Participants (N = 790) from 49 states
      completed a one-time online assessment that included the Life-Evaluation Index,
      Emotional and Physical Health Ladders, the Health Risk Intervention Assessment,
      and the Work Productivity and Activity Improvement Questionnaire for General
      Health. Life Evaluation and physical and emotional health were all inversely
      related to the number of health risk behaviors, with higher well-being scores
      associated with lower number of risk behaviors. Across the three Life Evaluation
      categories (Suffering, Struggling, and Thriving) the number of health risk
      behaviors decreased, productivity loss decreased, and emotional and physical
      health increased. The results add to previous research on how reducing multiple
      health risk behaviors can be combined with well-being, i.e., an emphasis on
      increasing life-evaluation, emotional and physical health, better functioning,
      and productivity.

PMID- 25074306
TI  - Exertional responses to sprint interval training: a comparison of 30-sec. and 60
      sec. conditions.
AB  - The purpose of this study was to assess the effect of sprint interval training on
      rating of perceived exertion. 20 healthy participants (11 men, 9 women; M age =
      23 yr.) completed a maximal cycle ergometer test and two high-intensity interval
      training cycling sessions. Each session utilized the same work-to-rest ratio
      (1:1), work intensity (90% max), recovery intensity (10% work intensity), and
      session duration (16 min.). Trials differed on duration of the interval segment,
      with a 30-sec. trial and a 60-sec. trial. Sessions required the same amount of
      total work over the duration of the trial. Rating of perceived exertion assessed
      before, during, and after exercise were higher for the 60-sec. trial than the 30
      sec. trial despite no difference in total work. High intensity interval training
      trials utilizing the same total external work but differing in interval length
      produced different ratings of perceived exertion. Perceived exertion is
      significantly higher for sessions of exercise that utilize longer work intervals.
      These findings suggest that shorter intervals may produce more favorable
      exertional responses that could positively affect future behavior.

PMID- 25074307
TI  - The bad apple effect and social value orientation in public-goods dilemmas:
      replication and extension of research findings.
AB  - Two studies were conducted to replicate and extend previous findings on the
      effect of uncooperative behavior on group cooperation (the "bad apple" effect).
      Study 1 (56 women, 40 men; M age = 23.5 yr.) manipulated information about
      contributions from the bad apple, controlling for overall contributions to a
      group account. Study 2 (50 women, 34 men; M age = 20.4 yr.) compared the effects
      of a bad apple and a good apple on cooperation. The social value orientation of
      participants was measured to explore individual differences in the bad apple
      effect. The results revealed a bad apple (a) decreased cooperation among
      individuals with proself and prosocial orientations in Study 1, and (b) had a
      greater effect than a good apple on those who were proself compared to prosocial
      in Study 2.

PMID- 25074308
TI  - Associations between trait emotional intelligence and loneliness in Chinese
      undergraduate students: mediating effects of self-esteem and social support.
AB  - Prior studies indicate that trait emotional intelligence (EI) is associated
      negatively with loneliness. However, the mechanisms underlying the relationship
      are not clear. This study assessed whether both self-esteem and social support
      mediated the associations between trait EI and loneliness. 469 Chinese
      undergraduate participants whose age ranged from 18 to 23 years (208 women) were
      asked to complete four self-report questionnaires, including the Wong Law
      Emotional Intelligence Scale, the Social and Emotional Loneliness Scale, the
      Rosenberg Self-esteem Scale, and the Multi-Dimensional Scale of Perceived Social
      Support. Analyses indicated that self-esteem and social support fully mediated
      the associations between trait EI and loneliness. Effect contrasts indicated that
      the specific indirect effect through social support was significantly greater
      than that through self-esteem. Moreover, a multiple-group analysis indicated that
      no path differed significantly by sex. These results suggest that social support
      is more important than self-esteem in the association between trait EI and
      loneliness. Furthermore, both sexes appear to share the same mechanism underlying
      this association.

PMID- 25074309
TI  - Happy Twitter tweets are more likely in American states with lower levels of
      resident neuroticism.
AB  - Relations between Big Five personality scores aggregated at the American state
      level and the happiness of Twitter tweet content emanating from each of the 50
      American states were explored with the 50 states as the units of analysis. Tweet
      happiness correlated negatively with Neuroticism, and the relation remained when
      partial correlation and multiple regression adjusted and controlled for state
      socioeconomic status, white population percent, and urban population percent. In
      contrast, state levels of Openness, Conscientiousness, Extraversion, and
      Agreeableness showed no relation to state levels of the happiness of tweet
      content.

PMID- 25074310
TI  - Lax decision criteria lead to negativity bias: evidence from the emotional stroop
      task.
AB  - Negativity bias means that negative information is usually given more emphasis
      than comparable positive information. Under signal detection theory, recent
      research found that people more frequently and incorrectly identify negative task
      related words as having been presented originally than positive words, even when
      they were not presented. That is, people have lax decision criteria for negative
      words. However, the response biases for task-unrelated negative words and for
      emotionally important words are still unclear. This study investigated response
      bias for these two kinds of words. Study 1 examined the response bias for task
      unrelated negative words using an emotional Stroop task. Proportions of correct
      recognition to negative and positive words were assessed by non-parametric signal
      detection analysis. Participants have lower (i.e., more lax) decision criteria
      for task-unrelated negative words than for positive words. Study 2 supported and
      expanded this result by investigating participants' response bias for highly
      emotional words. Participants have lower decision criteria for highly emotional
      words than for less emotional words. Finally, possible evolutionary sources of
      the response bias were discussed.

PMID- 25074311
TI  - Relations of children's proactive and reactive assertiveness to peer acceptance:
      moderating effects of social interest.
AB  - Previous studies on the social outcome of assertiveness reported mixed findings,
      failing to support the assumption that assertiveness promotes peer acceptance. In
      an attempt to provide explanations for the inconsistencies in prior findings,
      this study proposed making a distinction between proactive and reactive
      assertiveness and examined the moderating effects of social interest. A total of
      441 fifth and sixth graders (232 boys, 209 girls; M age = 10.6 yr., SD = 0.6)
      participated in the study. Results indicated that proactive assertiveness was
      positively related to peer acceptance regardless of social interest. By contrast,
      reactive assertiveness was positively related to peer acceptance but only when
      social interest is high. When social interest is low, it was negatively
      associated with peer acceptance.

PMID- 25074312
TI  - Factor structure of quality of life in adolescents.
AB  - The goal was to present the factor structure of subjective quality of life in
      adolescents, investigated by means of four questionnaires: the Youth Quality of
      Life-Research Version (YQOL-R), the Quality of Life Profile-Adolescent Version
      (QOLP-AV), the KIDSCREEN-52 Questionnaire, and the Quality of Life Questionnaire
      for Children and Adolescents (QLQ-CA). Two exploratory factor analyses conducted
      on the results obtained from two samples of adolescents: healthy, N = 252 (144
      girls, 108 boys), and chronically ill, suffering from several illnesses, N = 189
      (118 girls, 71 boys). Both factor analyses revealed four-factor solutions, each
      explaining about 60% of the total variance. The factor structure for the healthy
      group approximately reproduced the structures of the four questionnaires:
      Developmental quality of life (23%), Health and Well-being (16%), Relational
      quality of life (14%), and Ego strength (8%). The factor structure for the
      chronically ill group was similar for three factors: Developmental quality of
      life (22%), Harmony between the self and the environment (14%), and Coping and
      Support (12%), but different for another one: Health-related quality of life
      (10%). The discussion focuses on the specific nature of four aspects of quality
      of life observed in the healthy sample and their similarities to and differences
      from the factors in the chronic patients' sample.

PMID- 25074313
TI  - Assessment of learning and study strategies of university students in Qatar using
      an Arabic translation of the Learning and Study Strategies Inventory.
AB  - 413 (119 men, 294 women) undergraduate university students in Qatar completed an
      Arabic version of the Learning and Study Strategies Inventory (LASSI) measuring
      Anxiety, Attitude, Concentration, Information Processing, Motivation, Self
      testing, Selecting Main Ideas, Study Aids, Time Management, and Test Strategies.
      The students' learning and study strategies scores were similar to those reported
      in the literature. Factor analysis indicated the same general factors as in the
      original study. Internal consistency estimates ranged from .62 to .88. Nine of
      the 10 scales (i.e., all with the exception of the Study Aids) significantly
      correlated with students' GPAs. Scores obtained from these scales provide valid
      assessments of Qatar University students' use of learning and study strategies
      related to skill, will, and self-regulation components of strategic learning and
      also academic achievement. There also were statistically significant differences
      between higher and lower achieving students in their learning and study
      strategies. This study also explored the use of the LASSI as a predictive measure
      of academic achievement. Anxiety and test strategies were significant predictors
      of academic achievement as measured by students' GPA.

PMID- 25074314
TI  - Membership in fraternities and sororities, depression, and suicidal ideation.
AB  - College student membership in fraternities/sororities may have positive or
      negative effects on their behavior. This study investigated the relationships
      between fraternity/sorority membership, depression, and suicidal behavior. 293
      undergraduate students (232 women, 61 men; M age = 22.6 yr., SD = 1.5, range = 18
      24; 127 sorority sisters, 35 fraternity brothers) from a rural state college
      participated in the study. Depression, self-esteem and perceived social support
      were measured with the Beck Depression Inventory, the Rosenberg Self-esteem
      Scale, and the Multidimensional Scale of Perceived Social Support, respectively.
      Depression and suicidal ideation correlated negatively with self-esteem and
      perceived social support, but were not correlated with membership in
      fraternities/sororities.

PMID- 25074315
TI  - Self-esteem is characterized as a positive or a negative attitude toward the self
      (Rosenberg, 1965, cited in Mruk, 2006)." [corrected].
AB  - Mathematics achievement and self-esteem of 238 Qatari elementary students (128
      girls, 110 boys) was assessed. In Grades 1 to 5, self-esteem was M = 14.3 (SD =
      2.7) and mathematics achievement was M = 68.1 (SD = 21.9). Results indicated boys
      had higher self-esteem. Mathematics achievement and sex explained seven percent
      of the variance in self-esteem.

PMID- 25074318
TI  - DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial
      function in patients with type 2 diabetes: EDGE study.
AB  - BACKGROUND: Alpha glucosidase inhibitor (GI) attenuates postprandial
      hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients
      with impaired glucose tolerance or type 2 diabetes. Dipeptidyl peptidase 4 (DPP
      4) inhibitors also attenuate PPH. PPH is one of the factors leading to
      endothelial dysfunction which is an early event in the pathogenesis of
      atherosclerosis. Furthermore, DPP-4 inhibitors protect endothelial function
      through a GLP-1-dependent mechanism. However, the impact of these two types of
      drugs on endothelial dysfunction in patients with type 2 diabetes has not been
      fully elucidated. We compared the effects of sitagliptin, a DPP-4 inhibitor, and
      voglibose, an alpha GI, on endothelial function in patients with diabetes.
      METHODS: We conducted a randomized prospective multicenter study in 66 patients
      with type 2 diabetes who did not achieve the treatment goal with sulfonylurea,
      metformin or pioglitazone treatment; 31 patients received sitagliptin treatment
      and 35 patients, voglibose treatment. The flow-mediated dilatation (FMD) of the
      brachial artery was measured in the fasting state at baseline and after 12 weeks
      of treatment. The primary endpoint was a change in FMD (DeltaFMD) from the
      baseline to the end of follow-up. The effects of sitagliptin and voglibose on FMD
      were assessed by ANCOVA after adjustment for the baseline FMD, age, sex, current
      smoking, diabetes duration and body mass index. Secondary efficacy measures
      included changes in HbA1c, GIP, GLP-1, C-peptide, CD34, lipid profile, oxidative
      stress markers, inflammatory markers and eGFR and any adverse events. RESULTS:
      DeltaFMD was significantly improved after 12 weeks of treatment in both groups,
      and there was no significant difference in DeltaFMD between the two groups. There
      were no significant differences in changes in HbA1c, GIP, GLP-1, C-peptide, lipid
      profile, oxidative stress marker, inflammatory marker and eGFR between the two
      groups. Compared with voglibose, sitagliptin significantly increased the
      circulating CD34, a marker of endothelial progenitor cells. Adverse events were
      observed in 5 patients in only the voglibose group (diarrhea 1, nausea 1, edema 2
      and abdominal fullness 1). CONCLUSIONS: Sitagliptin improved endothelial
      dysfunction just as well as voglibose in patients with type 2 diabetes.
      Sitagliptin had protective effects on endothelial function without adverse
      events. TRIAL REGISTRATION: registered at http://www.umin.ac.jp/ctrj/ under
      UMIN000003951.

PMID- 25074319
TI  - Mortality in severely injured children: experiences of a German level 1 trauma
      center (2002 - 2011).
AB  - BACKGROUND: Trauma in pediatric patients is a major cause of death. This study
      investigated differences between decedents and survivors. Furthermore, an
      analysis of preventable and potential preventable trauma deaths was conducted and
      errors in the acute trauma care were investigated. METHODS: All patients aged
      less than 16 years with an Injury Severity Score (ISS) >= 16 upon primary
      admission to the hospital between July 2002 and December 2011 were included in
      this study. Decedents were compared with survivors and an analysis of deceased
      children for preventable and potential preventable deaths was conducted. The
      acute trauma care was investigated regarding errors in treatment. RESULTS:
      Significant differences were found in Glasgow Coma Scale, Injury Severity Score,
      Revised Trauma Score, New ISS, Revised Injury Severity Classification, and Trauma
      and Injury Severity Score. Decedents had a worse head trauma with associated
      coagulopathy. The overall mortality rate was 13.4%. The majority of death
      occurred soon after arrival. No long term intensive care unit stay was found.No
      preventable but one potential preventable death was analyzed. Most errors
      occurred in fluid volume management and in a delay of starting the therapy for
      hemorrhage and coagulopathy.Prolonged preclinical rescue time and surgery time
      within the first 24 hours was found. CONCLUSIONS: Head trauma is the determinant
      factor for mortality in severely injured pediatric patients. Death occurred
      shortly after arrival and long term intensive care stays might be an exception.
      In treatment of severely injured children volume management, hemorrhage and
      coagulopathy management, rescue time, and total surgery time should receive more
      attention.

PMID- 25074321
TI  - The nature and importance of quality of therapeutic relationships in the delivery
      of palliative care to people with intellectual disabilities.
AB  - BACKGROUND: The importance of the therapeutic relationship in the delivery of
      palliative care is well recognised. Little has been published on the nature or
      quality of relationships formed between staff and patients with intellectual
      disabilities despite case reports suggesting that difficulties exist in providing
      palliative care to this group. AIMS: This study was part of a project that aimed
      to describe the delivery of palliative care to people with intellectual
      disabilities in a region of Ireland and to conduct a corporate assessment of
      palliative care need. We detail findings that explore the nature and importance
      of the quality of relationship in the delivery of care. METHODS: 91 staff from
      palliative care and intellectual disability services participated in 16 focus
      groups. FINDINGS: Staff valued their relationships with service users, and felt
      that the quality of their relationship affected its therapeutic potential.
      Participants described factors fundamental to the development of quality
      relationships. Palliative care and intellectual disability staff commented on the
      importance of trust, of continuity of relationship and of knowing the individual.
      However, palliative care staff admitted to difficulties in these areas when
      providing care to people with intellectual disabilities. It appeared that quality
      of care was affected in situations where staff failed to form authentic
      relationships. CONCLUSIONS: This study adds to our knowledge of the processes of
      delivery of care to people with intellectual disabilities. The description of
      difficulties experienced by palliative care staff gives us an opportunity to
      develop strategies to improve the quality of services provided.

PMID- 25074320
TI  - A supramolecular strategy for self-mobile adsorption sites in affinity membrane.
AB  - Disclosed here is the design of a novel supramolecular membrane with self-mobile
      adsorption sites for biomolecules purification. In the 3D micropore channels of
      membrane matrix, the ligands are conjugated onto the cyclic compounds in
      polyrotaxanes for protein adsorption. During membrane filtration, the adsorption
      sites can rotate and/or slide along the axial chain, which results in the
      enhanced adsorption capacity. The excellent performance of supra-molecular
      membrane is related with the dynamic working manner of adsorption sites, which
      plays a crucial role on avoiding spatial mismatching and short-circuit effect.
      The supra-molecular strategy described here has general suggestions for the
      "sites" involved technologies such as catalysis, adsorption, and sensors, which
      is of broad interest.

PMID- 25074322
TI  - A functional SNP catalog of overlapping miRNA-binding sites in genes implicated
      in prion disease and other neurodegenerative disorders.
AB  - The involvement of SNPs in miRNA target sites remains poorly investigated in
      neurodegenerative disease. In addition to associations with disease risk, such
      genetic variations can also provide novel insight into mechanistic pathways that
      may be responsible for disease etiology and/or pathobiology. To identify SNPs
      associated specifically with degenerating neurons, we restricted our analysis to
      genes that are dysregulated in CA1 hippocampal neurons of mice during early,
      preclinical phase of Prion disease. The 125 genes chosen are also implicated in
      other numerous degenerative and neurological diseases and disorders and are
      therefore likely to be of fundamental importance. We predicted those SNPs that
      could increase, decrease, or have neutral effects on miRNA binding. This group of
      genes was more likely to possess DNA variants than were genes chosen at random.
      Furthermore, many of the SNPs are common within the human population, and could
      contribute to the growing awareness that miRNAs and associated SNPs could account
      for detrimental neurological states. Interestingly, SNPs that overlapped miRNA
      binding sites in the 3'-UTR of GABA-receptor subunit coding genes were
      particularly enriched. Moreover, we demonstrated that SNP rs9291296 would
      strengthen miR-26a-5p binding to a highly conserved site in the 3'-UTR of gamma
      aminobutyric acid receptor subunit alpha-4. 

PMID- 25074323
TI  - Extending the surrogacy analogy: applying the advance directive model to
      biobanks.
AB  - Biobank donors and biobank governance face a conceptual challenge akin to
      clinical patients and their designated surrogate decision-makers, the necessity
      of making decisions and policies now that must be implemented under future
      unknown circumstances. We propose that biobanks take advantage of this parallel
      to learn lessons from the historical trajectory of advance directives and develop
      models analogous to current 'best practice' advance directives such as Values
      Histories and TheFive Wishes. We suggest how such models could improve biobanks'
      engagement both with communities and with individual donors by being more honest
      about the limits of current disclosure and eliciting information to ensure the
      protection of donor interests more robustly through time than current 'informed
      consent' processes in biobanking.

PMID- 25074324
TI  - Ultrasonographic features of uterus masculinus in six dogs.
AB  - Uterus masculinus (persistent Mullerian duct) is a vestigial embryological
      remnant of the paramesonephric duct system in males and has been associated with
      clinical signs such as dysuria, incontinence, tenesmus and urethral obstruction
      in dogs. The radiological appearance of cystic uterus masculinus in dogs has been
      described previously with the aid of retrograde positive or negative contrast
      cystography. The purpose of this retrospective study was to describe
      ultrasonographic features of confirmed or presumed uterus masculinus in a group
      of dogs with confirmed or presumed disease. Ultrasonographic findings were
      recorded based on a consensus opinion of two readers. A uterus masculinus was
      defined as cylindrical when no lumen was observed and tubular when it had lumen
      that was filled with anechoic fluid. Six dogs met the inclusion criterion with a
      mean age of 8 years and 9 months. Uterus masculinus appeared as single (four
      dogs) or two (two dogs) horn-like, tubular (four dogs) or cylindrical (two dogs)
      structures, originating from the craniodorsal aspect of the prostate gland and
      extending cranially. The walls of the uterus masculinus were isoechoic to the
      urinary bladder wall. The diameter of the observed uterus masculinus varied from
      0.3 cm to 1 cm. The length of the uterus masculinus varied from 2 cm to 6.5 cm
      but the cranial terminal end was not identified in two dogs. Concomitant
      prostatomegaly was seen in five dogs (83.3%) and urinary tract infection was
      noted in three dogs (50%). Findings indicated that uterus masculinus should be
      included as a differential diagnosis for male dogs with these ultrasonographic
      characteristics. 

PMID- 25074325
TI  - Malaria in Hadhramout, a southeast province of Yemen: prevalence, risk factors,
      knowledge, attitude and practices (KAPs).
AB  - BACKGROUND: Yemen is a Mediterranean country where 65% of its population is at
      risk of malaria, with 43% at high risk. Yemen is still in the control phase
      without sustainable reduction in the proportion of malaria cases. A cross
      sectional household survey was carried out in different districts in the
      southeast of the country to determine malaria prevalence and identify factors
      that impede progress of the elimination phase. METHODS: Blood specimens were
      collected from 735 individuals aged 1-66 years. Plasmodium species were detected
      and identified by microscopic examination of Giemsa-stained thick and thin blood
      smears. A household-based questionnaire was used to collect demographic,
      socioeconomic and environmental data. RESULTS: The overall prevalence of malaria
      was 18.8% with Plasmodium falciparum as the predominant species (99.3%), with a
      low rate of Plasmodium vivax detected (0.7%). The infection rate was higher in Al
      Raydah and Qusyer districts (21.8%) compared to Hajer district (11.8%). Fifty-two
      percent of the persons positive for Plasmodium were asymptomatic with low
      parasite density. The adults had a higher infection rate as compared to children.
      Univariate analysis identified those whose household's head are fishermen (OR =
      11.3, 95% CI: 3.13-40.5) and farmers (OR = 4.84, 95% CI: 1.73-13.6) as high-risk
      groups. A higher number of positive smears were observed in people living in
      houses with uncemented brick walls (OR = 2.1, 95% CI: 1.32-3.30), without access
      to toilets (OR = 1.6, 95% CI: 1.05-2.32), without a fridge (OR = 1. 6, 95% CI:
      1.05-2.30), or without TV (OR = 1. 6, (95% CI: 1.05-2.30). People living in
      houses with water collection points located less than 200 meters away were also
      at higher risk of acquiring malaria (OR = 1.6, 95% CI: 1.05-2.30). Knowledge
      about the importance of using insecticide-treated mosquito nets (ITNs) and indoor
      residual spraying (IRS) for prevention of malaria was 7% and 2%, respectively.
      CONCLUSIONS: Several environmental, socioeconomic and behavioral issues were
      discovered to be the contributing factors to the high prevalence of malaria in
      southeast Yemen. Novel strategies adapted to the local situations need to be
      established in order to improve the effectiveness of malaria control.

PMID- 25074326
TI  - Utilization of host-derived cysteine-containing peptides overcomes the restricted
      sulphur metabolism of Campylobacter jejuni.
AB  - The non-glycolytic food-borne pathogen Campylobacter jejuni successfully
      colonizes the intestine of various hosts in spite of its restricted metabolic
      properties. While several amino acids are known to be used by C. jejuni as energy
      sources, none of these have been found to be essential for growth. Here we
      demonstrated through phenotype microarray analysis that cysteine utilization
      increases the metabolic activity of C. jejuni. Furthermore, cysteine was crucial
      for its growth as C. jejuni was unable to synthesize it from sulphate or
      methionine. Our study showed that C. jejuni compensates this limited anabolic
      capacity by utilizing sulphide, thiosulphate, glutathione and the dipeptides
      gammaGlu-Cys, Cys-Gly and Gly-Cys as sulphur sources and cysteine precursors. A
      panel of C. jejuni mutants in putative peptidases and peptide transporters were
      generated and tested for their participation in the catabolism of the cysteine
      containing peptides, and the predicted transporter protein CJJ81176_0236 was
      discovered to facilitate the growth with the dipeptide Cys-Gly, Ile-Arg and Ile
      Trp. It was named Campylobacter peptide transporter A (CptA) and is the first
      representative of the oligopeptide transporter OPT family demonstrated to
      participate in the glutathione-derivative Cys-Gly catabolism in prokaryotes. Our
      study provides new insights into how host- and microbiota-derived substrates like
      sulphide, thiosulphate and short peptides are used by C. jejuni to compensate its
      restricted metabolic capacities. 

PMID- 25074328
TI  - Novel and highly potent antitumour natural products from cnidarians of marine
      origin.
AB  - This article covers the 2003-2012 literature published for marine natural
      products from the phylum Cnidaria. The focus is on new and highly potent
      antitumour substances, together with details related to the organism sourced. It
      describes 12 promising bioactives isolated from 7 species. 

PMID- 25074327
TI  - A review of the first 10 years of critical care aeromedical transport during
      operation iraqi freedom and operation enduring freedom: the importance of
      evacuation timing.
AB  - IMPORTANCE: Advances in the care of the injured patient are perhaps the only
      benefit of military conflict. One of the unique aspects of the military medical
      care system that emerged during Operation Iraqi Freedom and Operation Enduring
      Freedom has been the opportunity to apply existing civilian trauma system
      standards to the provision of combat casualty care across an evolving theater of
      operations. OBJECTIVES: To identify differences in mortality for soldiers
      undergoing early and rapid evacuation from the combat theater and to evaluate the
      capabilities of the Critical Care Air Transport Team (CCATT) and Joint Theater
      Trauma Registry databases to provide adequate data to support future initiatives
      for improvement of performance. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      review of CCATT records and the Joint Theater Trauma Registry from September 11,
      2001, to December 31, 2010, for the in-theater military medicine health system,
      including centers in Iraq, Afghanistan, and Germany. Of 2899 CCATT transport
      records, those for 975 individuals had all the required data elements. EXPOSURE:
      Rapid evacuation by the CCATT. MAIN OUTCOMES AND MEASURES: Survival as a function
      of time from injury to arrival at the role IV facility at Landstuhl Regional
      Medical Center. RESULTS: The patient cohort demonstrated a mean Injury Severity
      Score of 23.7 and an overall 30-day mortality of 2.1%. Mortality en route was
      less than 0.02%. Statistically significant differences between survivors and
      decedents with respect to the Injury Severity Score (mean [SD], 23.4 [12.4] vs
      37.7 [16.5]; P < .001), cumulative volume of blood transfused among the patients
      in each group who received a transfusion (P < .001), worst base deficit (mean
      [SD], -3.4 [5.0] vs -7.8 [6.9]; P = .02), and worst international normalized
      ratio (median [interquartile range], 1.2 [1.0-1.4] vs 1.4 [1.1-2.2]; P = .03)
      were observed. We found no statistically significant difference between survivors
      and decedents with respect to time from injury to arrival at definitive care.
      CONCLUSIONS AND RELEVANCE: Rapid movement of critically injured casualties within
      hours of wounding appears to be effective, with a minimal mortality incurred
      during movement and overall 30-day mortality. We found no association between the
      duration of time from wounding to arrival at Landstuhl Regional Medical Center
      with respect to mortality.

PMID- 25074329
TI  - Selective growth and ordering of SiGe nanowires for band gap engineering.
AB  - Selective growth and self-organization of silicon-germanium (SiGe) nanowires
      (NWs) on focused ion beam (FIB) patterned Si(111) substrates is reported. In its
      first step, the process involves the selective synthesis of Au catalysts in SiO2
      free areas; its second step involves the preferential nucleation and growth of
      SiGe NWs on the catalysts. The selective synthesis process is based on a simple,
      room-temperature reduction of gold salts (Au3+Cl4-) in aqueous solution, which
      provides well-organized Au catalysts. By optimizing the reduction process, we are
      able to generate a bidimensional regular array of Au catalysts with self-limited
      sizes positioned in SiO2-free windows opened in a SiO2/Si(111) substrate by FIB
      patterning. Such Au catalysts subsequently serve as preferential nucleation and
      growth sites of well-organized NWs. Furthermore, these NWs with tunable position
      and size exhibit the relevant features and bright luminescence that would find
      several applications in optoelectronic nanodevices.

PMID- 25074330
TI  - Application of Bayesian theory to the reporting of results in alcohol hair
      testing.

PMID- 25074331
TI  - Recurrent cerebral venous thrombosis associated with heterozygote
      methylenetetrahydrofolate reductase C677T mutation and sickle cell trait without
      homocysteinemia: an autopsy case report and review of literature.
AB  - Elevated blood homocysteine concentration and certain genetic mutations have been
      associated with increased risk for developing arterial and venous thrombosis. A
      common mutation of methylenetetrahydrofolate reductase, MTHFR C677T, has been
      associated with elevated homocysteine concentration and increased risk for
      developing thrombosis in homozygote carriers. Heterozygote carriers for this gene
      mutation, if associated with other major or minor risk factors for thrombophilia,
      appear to be prone to develop thrombosis. A postmortem genetic testing for common
      mutations resulting in thrombophilia should be performed in all individuals who
      die as a result of thrombosis, regardless of predisposing risk factors, to
      determine the true prevalence of mutations in these individuals, and to assess
      the true role of a certain mutation, such as heterozygote MTHFR C677T, in the
      pathogenesis of thrombosis. Postmortem genetic testing for common mutations
      associated with thrombophilia in selected cases has potentially life-saving
      importance to surviving family members. We report a case of recurrent cerebral
      venous thrombosis in a 19 year old male with history of sickle cell trait,
      obesity, and high normal blood homocysteine, who was heterozygote for MTHFR C677T
      mutation. 

PMID- 25074332
TI  - Direct observation of the spin texture in SmB6 as evidence of the topological
      Kondo insulator.
AB  - Topological Kondo insulators have been proposed as a new class of topological
      insulators in which non-trivial surface states reside in the bulk Kondo band gap
      at low temperature due to strong spin-orbit coupling. In contrast to other three
      dimensional topological insulators, a topological Kondo insulator is truly bulk
      insulating. Furthermore, strong electron correlations are present in the system,
      which may interact with the novel topological phase. By applying spin- and angle
      resolved photoemission spectroscopy, here we show that the surface states of SmB6
      are spin polarized. The spin is locked to the crystal momentum, fulfilling time
      reversal and crystal symmetries. Our results provide strong evidence that SmB6
      can host topological surface states in a bulk insulating gap stemming from the
      Kondo effect, which can serve as an ideal platform for investigating of the
      interplay between novel topological quantum states with emergent effects and
      competing orders induced by strongly correlated electrons. 

PMID- 25074333
TI  - Ride 'em cowboy! The therapeutics of virtual reality technology and simulation.

PMID- 25074334
TI  - Why has the safety and quality movement been slow to improve care?
AB  - Buist and Middleton lament that the safety and quality 'agenda' has failed to
      fundamentally alter the safety of healthcare systems, in part because of the
      disengagement of doctors from their responsibilities for patient safety . While
      there have been discernable improvements in the efficiency and effectiveness of
      care in some settings, patients still experience unacceptable harm and often
      struggle to have their voices heard; processes are not as efficient as they could
      be; and costs continue to rise at alarming rates while quality issues remain .
      Perhaps of most concern, recent public reports into health system failures
      continue to document a widespread lack of attentiveness to patient concerns, a
      culture of denial and widespread lack of professionalism . Alarmingly, clinician
      discontentment, cynicism and burn-out are reflected in antagonistic language by
      clinicians about the healthcare system and their patients. Taken together with
      the many dissatisfied and now more vocal patient groups, all point to an
      unprecedented crisis of faith in our healthcare systems which has been getting
      worse over past decade . This personal perspective aims to address the
      fundamental tensions that are keeping much of healthcare reform efforts from
      successfully transforming the culture and outcomes except at the margins. 

PMID- 25074335
TI  - Uncertainties in real-world decisions on medical technologies.
AB  - Patients, clinicians, payers and policy makers face substantial uncertainties in
      their respective healthcare decisions as they attempt to achieve maximum value,
      or the greatest level of benefit possible at a given cost. Uncertainties largely
      come from incomplete information at the time that decisions must be made. This is
      true in all areas of medicine because evidence from clinical trials is often
      incongruent with real-world patient care. This article highlights key
      uncertainties around the (comparative) benefits and harms of medical
      technologies. Initiatives and strategies such as comparative effectiveness
      research and coverage with evidence development may help to generate reliable and
      relevant evidence for decisions on coverage and treatment. These efforts could
      result in better decisions that improve patient outcomes and better use of scarce
      medical resources. 

PMID- 25074336
TI  - Exacerbations or complications? Redefining the concepts in COPD.

PMID- 25074337
TI  - Biological functionality of soyasaponins and soyasapogenols.
AB  - Soyasaponins are a group of structurally complex oleanane triterpenoids primarily
      found in soybeans and have diverse biological properties. The recent
      investigations and findings (since 2000) regarding the biological functions of
      soyasaponins and their aglycones, including their anti-inflammatory,
      antimutagenic, anticarcinogenic, antimicrobial, and hepato- and cardiovascular
      protective activities, are herein summarized. The primary conclusion is that the
      use of soyasaponins and soyasapogenols in functional foods should be considered. 

PMID- 25074338
TI  - Duplication of the lower third of the internal jugular vein - case report and
      surgical implications.

PMID- 25074340
TI  - Plant tolerance of flooding stress--recent advances.

PMID- 25074339
TI  - Peroxiredoxin II negatively regulates lipopolysaccharide-induced osteoclast
      formation and bone loss via JNK and STAT3.
AB  - AIMS: Lipopolysaccharide (LPS) is considered a prominent pathogenic factor in
      inflammatory bone diseases. LPS challenge contributes to the production of
      reactive oxygen species (ROS) in diverse inflammatory diseases. However, its
      mechanism remains to be clarified in bone. Thus, we investigated the critical
      mechanism of ROS in LPS-induced osteoclastogenesis and bone loss. RESULTS:
      Antioxidant prevented LPS-induced osteoclast formation via inhibition of nuclear
      factor of activated T-cells, cytoplasmic 1 (NFATc1) and c-Fos expression in
      preosteoclasts. Moreover, LPS-induced osteoclast formation via ROS was attenuated
      by treatment with c-Jun N-terminal protein kinase (JNK) inhibitor. Interestingly,
      LPS also activated signal transducer and activator of transcription 3 (STAT3),
      which is suppressed by antioxidants. We found that knockdown of STAT3 or use of a
      STAT3 inhibitor resulted in a significant reduction in interleukin-1 beta (IL
      1beta), interleukin-6 (IL-6), and nitric oxide (NO) production, followed by
      decreased osteoclast formation by LPS. Peroxiredoxin II (PrxII) is a member of
      the antioxidant enzyme family, and it plays a protective role against oxidative
      damage caused by ROS. In our study, ROS production and osteoclast formation by
      LPS was significantly enhanced in PrxII(-/-) cells. Moreover, JNK-mediated c-Fos
      and NFATc1 expression was promoted in PrxII(-/-) cells. Furthermore, STAT3
      activation and accompanying IL-1beta, IL-6, and NO production was also increased
      in PrxII(-/-) cells. Consistent with the in vitro result, PrxII-deficient mice
      showed increased osteoclast formation and bone loss by LPS challenge compared
      with wild-type mice. INNOVATION: For the first time, we showed that LPS-induced
      ROS signaling is dependent on the coordinated mechanism of JNK and STAT3 during
      osteoclastogenesis, which is negatively regulated by PrxII. CONCLUSION: We
      suggest that PrxII could be useful in the development of a novel target for
      inflammatory bone loss.

PMID- 25074341
TI  - Psychosocial telephone intervention for dementia caregivers: A randomized,
      controlled trial.
AB  - BACKGROUND: Identifying effective and accessible interventions for dementia
      caregivers is critical as dementia prevalence increases. OBJECTIVE: Examine the
      effects of a telephone-based intervention on caregiver well-being. DESIGN:
      Randomized, controlled trial. SETTING: Academic medical center. PARTICIPANTS: Two
      hundred and fifty distressed, family, dementia caregivers. INTERVENTION:
      Caregivers randomized to receive 16 telephone contacts over 6 months of either
      the Family Intervention: Telephone Tracking-Caregiver (FITT-C) or Telephone
      Support (TS). OUTCOME: Primary outcome variables were family caregivers'
      depressive symptoms, burden, and reactions to care recipients' behavior problems
      at 6 months. RESULTS: The FITT-C intervention resulted in significantly improved
      caregiver depressive symptoms (P = .003; 27% net improvement) and less severe
      reactions to care-recipient depressive behaviors (P = .009; 29% net improvement)
      compared with the control condition (TS). CONCLUSION: An entirely telephone-based
      intervention improves caregivers' depressive symptoms and reactions to behavior
      problems in the care recipient and is comparable with reported results of face-to
      face interventions.

PMID- 25074343
TI  - Functional performance, participation and autonomy after discharge from
      prosthetic rehabilitation: barriers, facilitators and outcomes.
AB  - OBJECTIVE: To examine functional performance, participation and autonomy after
      discharge from prosthetic rehabilitation and to identify the barriers and
      facilitators affecting these outcomes. DESIGN: Concurrent mixed-methods design.
      Quantitative and qualitative data were collected at discharge from
      rehabilitation, and 3 and 6 months later. The data were integrated during
      analysis. SUBJECTS: Thirteen patients with a unilateral lower limb amputation
      participating for the first time in prosthetic rehabilitation in a Dutch
      rehabilitation centre. METHODS: Functional performance was measured using the Two
      Minute Walk Test and L test, and participation and autonomy using the Impact on
      Participation and Autonomy questionnaire. Barriers and facilitators were
      identified in semi-structured interviews. RESULTS: After discharge, 9 out of 13
      patients declined in functional performance. The principal problems in
      participation were observed in the "autonomy outdoors" and "family role" domains.
      Many factors affected functioning and participation and many differences were
      observed in the way that factors acted as barriers or facilitators for individual
      patients. No time patterns were found for barriers and facilitators. CONCLUSION:
      Post-discharge, distinctive fluctuations were observed in functional performance
      and participation and autonomy in patients with lower limb amputation. It is
      recommended that patients are educated about these fluctuations and the barriers
      and facilitators identified in the environmental, personal and medical contexts.

PMID- 25074342
TI  - Dependence in Alzheimer's disease and service use costs, quality of life, and
      caregiver burden: the DADE study.
AB  - BACKGROUND: Most models determining how patient and caregiver characteristics and
      costs change with Alzheimer's disease (AD) progression focus on one aspect, for
      example, cognition. AD is inadequately defined by a single domain; tracking
      progression by focusing on a single aspect may mean other important aspects are
      insufficiently addressed. Dependence has been proposed as a better marker for
      following disease progression. METHODS: This was a cross-sectional observational
      study (18 UK sites). Two hundred forty-nine community or institutionalized
      patients, with possible/probable AD, Mini-Mental State Examination (3-26), and a
      knowledgeable informant participated. RESULTS: Significant associations noted
      between dependence (Dependence Scale [DS]) and clinical measures of severity
      (cognition, function, and behavior). Bivariate and multivariate models
      demonstrated significant associations between DS and service use cost, patient
      quality of life, and caregiver perceived burden. CONCLUSION: The construct of
      dependence may help to translate the combined impact of changes in cognition,
      function, and behavior into a more readily interpretable form. The DS is useful
      for assessing patients with AD in clinical trials/research.

PMID- 25074344
TI  - Synchronous airway lesions in children: an analysis of characteristics and
      comorbidities.
AB  - OBJECTIVES: To analyze the characteristics and the associated medical co
      morbidities in children with synchronous airway lesions (SALs) found during rigid
      bronchoscopy. METHODS: Retrospective case series and chart review of patients who
      were found to have more than one airway lesion after undergoing airway evaluation
      via rigid endoscopy at a tertiary care pediatric hospital between 2001 and 2011.
      Patient demographics, presence of associated non-airway pathologies, and the
      number and types of airway lesions were collected. For analysis, airway lesions
      were classified based on the anatomical subsites involved (supraglottic, glottic,
      subglottic, tracheal and bronchial). RESULTS: Out of 592 rigid bronchoscopies
      performed, there were 73 cases with SALs (12.3%). Of these, only 20% of patients
      were term infants without associated congenital anomalies. Over 70% of patients
      with SALs have combinations of lesions involving the trachea, subglottis and
      supraglottis. Neurological anomalies and GERD were both independently associated
      with a three-time increase in the odds of having synchronous involvement of these
      three anatomical subsites (OR 3.15, 95% CI 1.06-9.41; OR 3.0, 95% CI 1.05-8.50,
      respectively). Glottic lesions were present in 28.7% of patients. Prematurity and
      cardiac anomalies were both associated with tendency of doubling the odds of
      glottic lesions (OR 2.34, 95% CI 0.84-6.52; OR 2.0, 95% CI 0.76-5.60,
      respectively). Overall, almost 10% of newly diagnosed lesions in context of SALs
      required an additional intervention. CONCLUSIONS: The majority of patients with
      SALs are either born prematurely or have associated congenital anomalies. In SAL
      patients with associated neurological anomalies or GERD, the lesions are more
      likely to be localized to the supraglottis, subglottis and trachea whereas
      prematurity and cardiac anomalies could both be increasing the odds of a glottic
      lesion. High suspicious index should be kept in mind when rigid bronchoscopy is
      performed to not miss an associated lesion.

PMID- 25074345
TI  - Acute mastoiditis in children under 15 years of age in Southern Israel following
      the introduction of pneumococcal conjugate vaccines: a 4-year retrospective study
      (2009-2012).
AB  - OBJECTIVES: To describe the epidemiologic, microbiologic, clinical and
      therapeutic aspects of acute mastoiditis (AM) in children <15 years of age during
      the 4-year period (2009-2012) following the introduction of pneumococcal
      conjugate vaccines in Israel. PATIENTS AND METHODS: The medical records of all
      children with a discharge diagnosis of AM were reviewed. RESULTS: A total of 66
      AM episodes occurred in 61 patients. Forty-four (66.6%) cases occurred among
      patients <4 years, recent acute otitis media (AOM) history was reported in 27.1%
      and 28.8% patients received previous antibiotics for AOM. Postauricular swelling,
      postauricular sensitivity, protrusion of auricle and postauricular edema (93.8%,
      90.6%, 85.9% and 95.7%, respectively) were the most common signs of AM.
      Leukocytosis >15,000 WBC/mm(3) was found in 39 (59.1%) cases. Cultures were
      performed in 52/66 episodes (positive in 27, 51.92% episodes), with recovery of
      32 pathogens. The most frequently isolated pathogens were Streptococcus
      pneumoniae (15/52, 28.85%), Streptococcus pyogenes (9, 17.3%) and nontypeable
      Haemophilus influenzae (5, 9.62%). Eight (53.3%) S. pneumoniae isolates were
      susceptible to penicillin. Mean incidence of overall and pneumococcal AM were
      11.1 and 2.58 cases/100000, with no significant changes during the study years.
      Surgical intervention was required in 19 (28.8%) patients. CONCLUSIONS: (1) AM
      occurs frequently in patients without previous AOM history and with no previous
      antibiotic treatment; (2) S. pneumoniae and S. pyogenes continued to be the main
      etiologic agents of AM during the postvaccination period; (3) No changes were
      recorded in overall AM incidence and in pneumococcal AM incidence during the
      postvaccination period.

PMID- 25074346
TI  - Statin use and thyroid cancer: a population-based case-control study.
AB  - OBJECTIVE: Several observational studies raised the possibility that the use of
      statins may decrease the overall risk of cancer and of specific cancers. This
      study aimed to evaluate the association of statin use with thyroid cancer based
      on a population-based data set. DESIGN: The data for this case-control study were
      sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included
      500 subjects with thyroid cancer as cases and 2500 gender- and age-matched
      subjects without thyroid cancer as controls. We used a conditional logistic
      regression to calculate the odds ratio (OR) and its corresponding 95% confidence
      interval (CI) for having previously used statins between cases and controls.
      RESULTS: The OR of prior statin use for cases was 1.39 (95% CI = 1.08-1.78)
      compared to controls, and thyroid cancer was significantly associated with
      previous regular statin use (OR = 1.40, 95% CI = 1.05-1.86). However, thyroid
      cancer was not significantly associated with previous irregular statin use (OR =
      1.35; 95% CI = 0.88-2.07). Furthermore, the significant association between
      thyroid cancer and previous statin use only existed for females (OR: 1.43; 95%
      CI: 1.07-1.90) but not for males (OR: 1.28; 95% CI: 0.75-2.17). CONCLUSIONS: We
      concluded that statin use was associated with thyroid cancer in female patients.

PMID- 25074347
TI  - Novel superconducting skutterudite-type phosphorus nitride at high pressure from
      first-principles calculations.
AB  - State of the art variable composition structure prediction based on density
      functional theory demonstrates that two new stoichiometries of PN, PN3 and PN2,
      become viable at high pressure. PN3 has a skutterudite-like Immm structure and is
      metastable with positive phonon frequencies at pressures between 10 and 100 GPa.
      PN3 is metallic and is the first reported nitrogen-based skutterudite. Its
      metallicity arises from nitrogen p-states which delocalise across N4 rings
      characteristic of skutterudites, and it becomes a good electron-phonon
      superconductor at 10 GPa, with a Tc of around 18 K. The superconductivity arises
      from strongly enhanced electron-phonon coupling at lower pressures, originating
      primarily from soft collective P-N phonon modes. The PN2 phase is an insulator
      with P2/m symmetry and is stable at pressures in excess of 200 GPa. 

PMID- 25074348
TI  - Modified open-door laminoplasty for the surgical treatment of cervical
      spondylotic myelopathy in elderly patients. Biomechanical concerns.

PMID- 25074349
TI  - Response to Modified open-door laminoplasty for the surgical treatment of
      cervical spondylotic myelopathy in elderly patients. Biomechanical concerns.

PMID- 25074350
TI  - Hans Brun: a Swiss pioneer in the surgery of the spinal cord, brain and herniated
      lumbar disc.
AB  - INTRODUCTION: Toward the end of the nineteenth century, it was Gowers, Horsley
      and Macewen who first reported successful surgical procedures for the treatment
      of subdural extramedullary tumors. Following this, Church and Eisendrath as well
      as Putnam and Warren reported unsuccessful attempts to treat subpial spinal
      pathologies in their patients. Only at the beginning of the twentieth century did
      reports of successful interventions of this type accumulate. In the analysis of
      these case reports, the authors noticed a certain lack of accuracy about the
      anatomical allocations and descriptions of intra- and extramedullary spinal
      lesions. From this, the question of who actually carried out the pioneering works
      in the early twentieth century in the field of surgery of intramedullary
      pathologies arose. METHODS: Analysis of the relevant original publications of
      Hans Brun and research on the poorly documented information about his life
      history by personally contacting contemporary relatives. RESULTS: The literature
      analysis showed that the Swiss neurologist Otto Veraguth and surgeon Hans Brun
      made fundamental contributions to subpial spinal cord surgery at the very
      beginning of the last century that remain valid today. According to our research,
      Hans Brun should be remembered as the third surgeon (after von Eiselsberg and
      Elsberg) who successfully removed an intramedullary lesion in a patient.
      CONCLUSION: Brun should be remembered as an early and successful surgeon in this
      specialized field. His operative work is described in detail in this article. At
      the same time, his achievements in the fields of brain and disc herniation
      surgery are presented.

PMID- 25074351
TI  - Comparison of the effects of three oral bisphosphonate therapies on the
      peripheral skeleton in postmenopausal osteoporosis: the TRIO study.
AB  - We compared the effects of oral alendronate, ibandronate and risedronate on the
      central and peripheral skeleton over 2 years. We report differences in effect on
      the central skeleton but not on the peripheral skeleton. Greater effects were
      observed for ibandronate (and alendronate) than risedronate at the spine but not
      the hip. INTRODUCTION: Generally, comparative clinical trials of bisphosphonates
      have examined changes in bone within central skeletal regions. We have examined
      the effects of bisphosphonate treatment on the peripheral skeleton. METHODS: We
      conducted a 2-year, open-label, parallel randomised control trial of three orally
      administered bisphosphonates, at their licensed dose, to examine and compare
      their effects on the peripheral skeleton using multiple modes of measurement. We
      studied 172 postmenopausal women (53-84 years) who had either a bone mineral
      density (BMD) T-score of  <= -2.5 at the spine and/or total hip or  < -1.0 at
      either site plus a previous low trauma fracture. Participants were randomised to
      receive either (i) ibandronate 150 mg/month, (ii) alendronate 70 mg/week or (iii)
      risedronate 35 mg/week, plus calcium (1,200 mg/day) and vitamin D (800 IU/day),
      for 2 years. Premenopausal women (33-40 years, n = 226) were studied to monitor
      device stability. RESULTS: We measured central BMD of the lumbar spine, total
      hip, total body and forearm using dual-energy X-ray absorptiometry. We measured
      calcaneus BMD (using dual-energy X-ray absorptiometry plus laser), radius and
      tibia BMD (using peripheral quantitative computed tomography), finger BMD (using
      radiographic absorptiometry), and phalangeal and calcaneal ultrasound variables
      (using quantitative ultrasound). Mixed effects regression models were used to
      evaluate effects of time and treatment allocation on BMD change. By 2 years,
      there were significant increases (p < 0.05) in central BMD sites (lumbar spine,
      total hip). In the peripheral skeleton, only significant changes in calcaneus
      BMD, 33 % total radius BMD and quantitative ultrasound (QUS)-2 broadband
      ultrasound attenuation (BUA) were evident for women receiving oral
      bisphosphonates. CONCLUSIONS: The increases in lumbar spine and total body BMD
      were greater with ibandronate and alendronate than with risedronate. Treatment
      effects on peripheral measurements did not differ between the three
      bisphosphonates.

PMID- 25074353
TI  - Isolation and characterization of putative endophytic bacteria antagonistic to
      Phoma tracheiphila and Verticillium albo-atrum.
AB  - A collection of 200 bacterial isolates recovered from citrus plants (Citrus
      limon, Citrus sinensis, and Citrus reticulata), Medicago truncatula and Laurus
      nobilis, was established. In vitro screening indicated that 28 isolates exhibited
      an inhibitory activity against the vascular pathogens Phoma tracheiphila and
      Verticillium albo-atrum. Isolates were screened according to their hydrolytic
      activities, plant growth-promoting bacteria (PGPB) abilities, as well as for the
      presence of nonribosomal peptide synthetase (NRPS) genes responsible of the
      lipopeptide biosynthesis. The results were positive for 16 isolates which
      exhibited at least two PGPB activities and a single NRPS gene. Genetic diversity
      of the selected isolates was studied using random amplified polymorphic DNA
      (RAPD) and repetitive element PCR (REP) tools that showed clustering of strains
      into three major groups (I, II, and III) (i, ii, and iii), respectively.
      Clustering was further confirmed by the 16S rDNA sequencing that assigned nine
      isolates to Bacillus velezensis, four isolates to Bacillus methyltrophicus, one
      isolate to Bacillus amyloliquefaciens, and two isolates to Bacillus mojavensis.
      Organ-bacterial genotype interaction as well as positive correlation with NRPS
      genes are discussed. 

PMID- 25074352
TI  - Estrogen alone or in combination with parathyroid hormone can decrease vertebral
      MEF2 and sclerostin expression and increase vertebral bone mass in ovariectomized
      rats.
AB  - The study is about the regulatory effects of estrogen and parathyroid hormone
      (PTH) on sclerostin, a protein that inhibits the Wnt/beta-catenin pathway. The
      results indicate that estrogen may down-regulate sclerostin expression and that
      estrogen displays synergistic action with PTH. These results provide a new
      perspective on the relationship between estrogen and bone. PURPOSE: To
      investigate whether estrogen can down-regulate SOST and MEF2 (myocyte enhancer
      factor 2) expression and whether co-treatment with estrogen and PTH has a
      stronger effect on suppressing SOST than PTH applied alone in ovariectomized
      rats. METHODS: Forty-three-month-old virgin female Sprague-Dawley (SD) rats were
      ovariectomized and divided into four groups (n = 10). Another ten age-matched
      rats received sham operations as controls. After allowing 8 weeks for the
      development of vertebral osteopenia, the rats were administered the drug
      intervention. For this intervention, the estrogen group was subcutaneously
      injected with 17beta-estradiol at 25 MUg/kg body weight, the PTH group was
      injected with 80 MUg/kg synthetic human PTH (1-34), and the co-treatment group
      was concurrently treated with PTH and estrogen at the above dosage. The OVX group
      and sham group were treated with vehicle. The drug treatment was conducted for 12
      weeks. After the lumbar spine bone mineral density (BMD) was measured, the rats
      were sacrificed, and the lumbar spine and blood were collected for qPCR, Western
      blot, immunohistochemistry and other tests. RESULTS: Estrogen can down-regulate
      MEF2 and sclerostin expression, and co-treatment with estrogen and PTH has a
      stronger effect on suppressing MEF2 and SOST mRNA than PTH alone. The co
      treatment group displayed slightly higher bone mass and biomechanical properties
      than the PTH group, but the differences were not significant. CONCLUSIONS:
      Estrogen appears to be a regulator of sclerostin, and the effect may involve
      suppressing MEF2s. Combined treatment with PTH and estrogen is not more
      beneficial for vertebral bone mass and strength than treatment with PTH alone in
      ovariectomized rats.

PMID- 25074354
TI  - Preference elicitation tool for abnormal uterine bleeding treatment: a randomized
      controlled trial.
AB  - BACKGROUND: It is estimated that one-third of women will experience abnormal
      menstrual bleeding. The majority of these cases are not due to cancer or
      pregnancy complications and, as a result, women are faced with a variety of
      treatment alternatives, the selection of which is largely dependent on personal
      preferences for care rather than clinical outcomes. OBJECTIVE: This randomized
      trial was designed to evaluate a preference elicitation tool to promote physician
      patient collaborative decision making for treatment of abnormal uterine bleeding
      (AUB). METHODS: Adaptive conjoint analysis (ACA) was used to create a preference
      elicitation tool in English and in Spanish. Women with AUB were enrolled to the
      study and randomly assigned to ACA or usual counseling at the initial clinic
      visit at four clinics (three in Indianapolis, IN, USA, and one in Southern Pines,
      NC, USA). The ACA tool elicited preferences across eight attributes: treatment
      efficacy; sexual function; medical care; cost; fertility; frequency of medication
      use; permanence; and recovery time. t tests were used to compare differences in
      the primary outcomes of decision regret and treatment satisfaction at the follow
      up visit. The study was designed to have 80 % power to detect significant
      differences between groups for the primary outcomes of regret and satisfaction.
      RESULTS: Women were enrolled in the study between September 2009 and March 2012.
      183 participants were randomized to ACA and 191 to usual counseling. Overall,
      mean (standard deviation) treatment satisfaction was high at 35.71 (9.72) (scale
      of 0-44), and decision regret was low at 25.9 (21.0) (scale of 0-100), creating
      ceiling effects for the selected outcome variables; there were no significant
      differences between the ACA and control groups at the follow-up assessment. There
      was a strong inverse relationship between age and decision regret (p = 0.007).
      Exploratory subgroup analysis in the youngest quartile comprising 64 women aged
      19-35 years showed a statistically non-significant difference in mean regret
      scores for the ACA group versus usual counseling (24.6 vs. 34.6, respectively; p
      = 0.08). CONCLUSIONS: A preference elicitation tool at the initial consultation
      visit did not reduce decision regret or improve treatment satisfaction among
      patients with AUB; however, there is a need for additional research to further
      understand this tool's potential role in promoting collaborative decision making,
      which may be particularly important among younger women.

PMID- 25074355
TI  - The development of capability measures in health economics: opportunities,
      challenges and progress.
AB  - Recent years have seen increased engagement amongst health economists with the
      capability approach developed by Amartya Sen and others. This paper focuses on
      the capability approach in relation to the evaluative space used for analysis
      within health economics. It considers the opportunities that the capability
      approach offers in extending this space, but also the methodological challenges
      associated with moving from the theoretical concepts to practical empirical
      applications. The paper then examines three 'families' of measures, Oxford
      Capability instruments (OxCap), Adult Social Care Outcome Toolkit (ASCOT) and
      ICEpop CAPability (ICECAP), in terms of the methodological choices made in each
      case. The paper concludes by discussing some of the broader issues involved in
      making use of the capability approach in health economics. It also suggests that
      continued exploration of the impact of different methodological choices will be
      important in moving forward. 

PMID- 25074356
TI  - Venous thromboembolism in hospitalized patients: an updated analysis of missed
      opportunities for thromboprophylaxis at a university-affiliated tertiary care
      center.
AB  - Thromboprophylaxis remains often underused in hospitalized patients. In 2001, a
      cohort study done at our institution, a tertiary care center in Montreal, Canada,
      showed that 67.7% of VTE cases necessitating thromboprophylaxis were potentially
      preventable with adequate use of American College of Chest Physicians (ACCP)
      guidelines. Following implementation of an institution-wide policy in 2005, we
      assessed the changes in the rate of potentially preventable VTE. We conducted a
      retrospective cohort study including all hospitalized patients with objectively
      diagnosed VTE in 2010 at our institution. Each case was classified as preventable
      (thromboprophylaxis indicated but inadequately administered), non-preventable
      (thromboprophylaxis indicated and correctly administered), spontaneous
      (thromboprophylaxis not indicated), and ineligible (contraindication to
      thromboprophylaxis). The results were compared to those obtained in 2001. Of the
      230 cases of VTE, 55 cases were classified as potentially preventable (23.9%), 85
      were non-preventable (37.0%), 74 were spontaneous (32.2%) and 16 (7.0%) were
      ineligible. Of the 140 cases requiring thromboprophylaxis, 39.3% were potentially
      preventable. The potentially preventable cases were mostly due to omission of
      thromboprophylaxis (50.9%), occurred during general medical admissions (74.5%),
      and the most common VTE risk factor was cancer (47.2%). In conclusion, we
      demonstrate a lower frequency of potentially preventable cases in 2010 compared
      to 2001 (39.3% vs 67.7%, respectively), partially due to physician education and
      adoption of an institution-wide policy. However, patients with medical
      indications for thromboprophylaxis, particularly those with cancer, are more
      prone to having preventable VTE, indicating an area for potential improvement. 

PMID- 25074357
TI  - Metal-ligand bifunctional reactivity and catalysis of protic N-heterocyclic
      carbene and pyrazole complexes featuring beta-NH units.
AB  - Metal-ligand bifunctional cooperation has attracted much attention because it
      offers a powerful methodology to realize a number of highly efficient and
      selective catalysts. In this article, recent developments in the metal-ligand
      cooperative reactions of protic N-heterocyclic carbene (NHC) and pyrazole
      complexes bearing an acidic NH group at the position beta to the metal are
      surveyed. Protic 2-pyridylidenes as related cooperating non-innocent ligands are
      also described. 

PMID- 25074358
TI  - Association between genetic variants in PNPLA3 and serum adiponectin.

PMID- 25074359
TI  - Biological effects of sol-gel derived ZrO2 and SiO2/ZrO2 coatings on stainless
      steel surface--In vitro model using mesenchymal stem cells.
AB  - The objective of this study was to determine biocompatibility of zirconia-based
      coatings obtained by the sol-gel method. Two matrices, ZrO2 and SiO2/ZrO2, were
      created and applied on stainless steel type 316L with dip-coating technique. The
      morphology and topography of biomaterials' surface were characterized using
      energy-dispersive X-ray spectroscopy and atomic force microscopy, while chemical
      composition was analyzed by Raman spectroscopy. Additionally, wettability and
      surface free energy were characterized. Biocompatibility of obtained biomaterials
      was evaluated using an in vitro model employing mesenchymal stem cells (MSCs) of
      adipose and bone marrow origin. Biological analysis included determination of
      proliferation activity and morphology of MSCs in cultures on synthesized
      biomaterials. Osteoinductive properties of biomaterials were determined both in
      non-osteogenic, as well as osteogenic conditions. The results showed that
      investigated biomaterials exerted different impact on MSCs. Biomaterial with ZrO2
      layer was more biocompatible for adipose-derived MSCs, while SiO2/ZrO2 layer
      promoted proliferation of bone marrow derived MSCs. Moreover, hybrid coating
      exhibited greater osteoinductive properties than ZrO2 coating, both on cultures
      with adipose-derived stromal (stem) cells and bone marrow stromal cells. Observed
      biological effects may result not only from different chemical composition, but
      also from diverse wettability. The ZrO2 coating was characterized as hydrophobic
      layer, while SiO2/ZrO2 exhibited hydrophilic properties. The results obtained
      suggest that behavior of MSCs in response to the biomaterial may vary depending
      on their origin, therefore we postulate, that screening analysis of implants'
      biocompatibility, should incorporate model applying both adipose- and bone marrow
      derived MSCs. 

PMID- 25074360
TI  - Can ultrasound be used to predict malignancy in patients with a thyroid nodule
      and an indeterminate fine-needle aspiration biopsy?
AB  - PURPOSE: The purpose of this study was to evaluate whether ultrasonography is
      helpful in predicting malignancy in patients with a thyroid nodule and
      atypia/follicular lesion of undetermined significance (AFLUS). METHODS: All
      patients with a preoperative ultrasound who underwent thyroidectomy for a nodule
      with AFLUS comprised the study population. A blinded review of gray-scale and
      color-Doppler sonographic images of the thyroid nodule was performed by an expert
      sonographer; results were compared with the original interpretation and were
      correlated with histopathology. All images were reviewed for hypoechogenicity,
      irregular margins, shape that was taller than wide, micro and
      macrocalcifications, absent halo, and intranodular hypervascularity. RESULTS:
      From 2010 to 2012, 61 patients underwent thyroidectomy for AFLUS with an
      ultrasound examination for review; 6 (10%) with cancer. Nodule shape that was
      taller than wide, was associated with cancer (P < .05). The original sonographer
      commented on an average of two of seven features important in assessment of a
      thyroid nodule. CONCLUSION: With the exception of nodule height greater than
      width, sonographic criteria were not helpful in deciding which patients with
      AFLUS should undergo thyroidectomy. Thyroidectomy is recommended in lieu of
      repeat biopsy for a nodule that is taller than wide. Standardized sonographic
      reporting should be implemented.

PMID- 25074361
TI  - Discussion.

PMID- 25074362
TI  - p-Type dopant incorporation and surface charge properties of catalyst-free GaN
      nanowires revealed by micro-Raman scattering and X-ray photoelectron
      spectroscopy.
AB  - Micro-Raman scattering and X-ray photoelectron spectroscopy were employed to
      investigate Mg-doped GaN nanowires. With the increase of Mg doping level,
      pronounced Mg-induced local vibrational modes were observed. The evolution of
      longitudinal optical phonon-plasmon coupled mode, together with detailed X-ray
      photoelectron spectroscopy studies, show that the near-surface region of
      nanowires can be transformed from weakly n-type to p-type with the increase of Mg
      doping. 

PMID- 25074363
TI  - Genetic architectures of ADME genes in five Eurasian admixed populations and
      implications for drug safety and efficacy.
AB  - BACKGROUND: Drug absorption, distribution, metabolism and excretion (ADME)
      contribute to the high heterogeneity of drug responses in humans. However, the
      same standard for drug dosage has been applied to all populations in China
      although genetic differences in ADME genes are expected to exist in different
      ethnic groups. In particular, the ethnic minorities in northwestern China with
      substantial ancestry contribution from Western Eurasian people might violate such
      a single unified standard. METHODS: In this study, we used Affymetrix SNP Array
      6.0 to investigate the genetic diversity of 282 ADME genes in five northwestern
      Chinese minority populations, namely, Tajik, Uyghur, Kazakh, Kirgiz and Hui, and
      attempted to identify the highly differential SNPs and haplotypes and further
      explore their clinical implications. RESULTS: We found that genetic diversity of
      many ADME genes in the five minority groups was substantially different from
      those in the Han Chinese population. For instance, we identified 10 functional
      SNPs with substantial allele frequency differences, 14 functional SNPs with
      highly different heterozygous states and eight genes with significant haplotype
      differences between these admixed minority populations and the Han Chinese
      population. We further confirmed that these differences mainly resulted from the
      European gene flow, that is, this gene flow increased the genetic diversity in
      the admixed populations. CONCLUSIONS: These results suggest that the ADME genes
      vary substantially among different Chinese ethnic groups. We suggest it could
      cause potential clinical risk if the same dosage of substances (eg, antitumour
      drugs) is used without considering population stratification.

PMID- 25074364
TI  - Biomonitoring of heavy metals (Cd, Hg, and Pb) and metalloid (As) with the
      Portuguese common buzzard (Buteo buteo).
AB  - The accumulation of heavy metals in the environment may have a wide range of
      health effects on animals and humans. Thus, in this study, the concentrations of
      arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) in the blood and tissues
      (liver and kidney) of Portuguese common buzzards (Buteo buteo) were determined by
      inductively coupled plasma-mass spectrometer (ICP-MS) in order to monitor
      environmental pollution to these elements. In general, Hg and As were the
      elements which appeared in the highest and lowest concentrations, respectively. A
      highest percentage of non-detected concentration was found for blood Cd (94.6 %)
      but, in turn, it was the only metal that was detected in all kidney samples. The
      kidney was the analyzed sample which showed the highest concentrations of each
      element evaluated. Statistically, significant differences among blood, liver, and
      kidney samples were observed for As and Cd (P < 0.05). Cd concentrations in
      kidney and liver varied significantly with age: Adults showed higher hepatic and
      renal Cd concentrations than juveniles. Blood Pb concentration seems to show an
      association with the hunting season. Although raptors are at the top of the food
      chain and are thus potentially exposed to any biomagnification processes that may
      occur in a food web, the individuals evaluated in this study generally had low
      levels of heavy metals in blood and tissues. However, chronic exposure to these
      metals was verified. The results presented here lend weight to arguments in favor
      of continuous biomonitoring of metals and metalloids, since heavy metals may
      accumulate to levels that will pose a risk to both human health and the
      environment. 

PMID- 25074365
TI  - Impacts of ecological water conveyance on groundwater dynamics and vegetation
      recovery in the lower reaches of the Tarim River in northwest China.
AB  - The ecological water conveyance project (EWCP) in the lower reaches of the Tarim
      River provided a valuable opportunity to study hydro-ecological processes of
      desert riparian vegetation. Ecological effects of the EWCP were assessed at large
      spatial and temporal scales based on 13 years of monitoring data. This study
      analyzed the trends in hydrological processes and the ecological effects of the
      EWCP. The EWCP resulted in increased groundwater storage-expressed as a general
      rise in the groundwater table-and improved soil moisture conditions. The change
      of water conditions also directly affected vegetative cover and the phenology of
      herbs, trees, and shrubs. Vegetative cover of herbs was most closely correlated
      to groundwater depth at the last year-end (R = 0.81), and trees and shrubs were
      most closely correlated to annual average groundwater depth (R = 0.79 and 0.66,
      respectively). The Normalized Difference Vegetation Index (NDVI) responded to
      groundwater depth on a 1-year time lag. Although the EWCP improved the NDVI, the
      study area is still sparsely vegetated. The main limitation of the EWCP is that
      it can only preserve the survival of existing vegetation, but it does not
      effectively promote the reproduction and regeneration of natural vegetation. 

PMID- 25074366
TI  - Colour Doppler ultrasound findings in the nail in cystic fibrosis.

PMID- 25074368
TI  - Development of the AANS/CNS joint Section on Tumors: challenges and
      opportunities.
AB  - Over the 30 years since the formation of the AANS/CNS Section on Tumors, the
      breadth and scope of our activities have continued to expand. An initial focus on
      education and collaboration between those members of the neurosurgical community
      dedicated to the care of patients with neurological tumors has broadened to
      include development of international relationships, participation in clinical
      trials and efforts to define standards of care and quality metrics. As we
      navigate the rapidly changing environment of health care, the Section on Tumors
      will occupy a central role in promoting advocacy, establishing collaboration,
      providing education, and supporting research for the community of neurosurgeons
      dedicated to the care of patients with neurological tumors. This article will
      provide an update and status report on the development of the Section on Tumors,
      followed by a brief discussion of the challenges and opportunities emerging at
      the onset of our fourth decade of service.

PMID- 25074367
TI  - [Merkel cell carcinoma].
AB  - Merkel cell carcinoma (MCC, cutaneous neuroendocrine carcinoma) is a rare form of
      tumor of unclear histogenesis which predominantly occurs in elderly patients on
      areas exposed to the sun. A higher incidence and occurrence in younger people is
      predominantly found in immunosuppressed persons which is why a pathogenetic role
      is also attributed to immunosuppression in addition to ultraviolet (UV)
      radiation. Additionally, in 80% of cases clonally integrated polyomavirus (Merkel
      cell polyomavirus, MCPyV) could be detected. Clinically MCC represents an
      uncharacteristic tumor. Histopathologically, monomorphic dermal and/or
      subcutaneous nodes are found consisting of round or oval medium sized cells with
      a vesicular nucleus and sparse cytoplasm. The neoplastic cells of MCC express
      cytokeratin (CK) 20 with a dot-like perinuclear accentuation. In addition, pan
      CK, neuroendocrine markers (e.g. chromogranin A and synaptophysin), neurofilament
      proteins, CD56, CD57, Bcl-2, TdT and PAX-5 are immunohistochemically positive. In
      most cases CM2B4, an antibody against MCPyV is also positive. Expression of p63
      has been observed in some of the cases and in some studies was associated with a
      favorable prognosis. The markers thyroid transcription factor 1, mammalian
      achaete scute complex like 1, vimentin, S-100 and CK7 are not normally expressed
      by MCC. The prognosis is primarily dependent on tumor size and the lymph node
      status. The presence of intralymphatic tumor complexes is associated with a
      higher rate of local recurrence and lymph node metastasis. A larger number of
      intratumoral cytotoxic T-lymphocytes is accompanied by a favorable prognosis and
      the presence of > 50% of K-67+ neoplastic cells with an unfavorable prognosis.
      Further morphological, phenotypical and genetic factors have not yet been
      validated in larger cohorts with respect to the prognostic relevance.

PMID- 25074370
TI  - How to bury the dead: elimination of apoptotic hair cells from the hearing organ
      of the mouse.
AB  - Hair cell death is a major cause of hearing impairment. Preservation of surface
      barrier upon hair cell loss is critical to prevent leakage of potassium-rich
      endolymph into the organ of Corti and to prevent expansion of cellular damage.
      Understanding of wound healing in this cytoarchitecturally complex organ requires
      ultrastructural 3D visualization. Powered by the serial block-face scanning
      electron microscopy, we penetrate into the cell biological mechanisms in the
      acute response of outer hair cells and glial-like Deiters' cells to ototoxic
      trauma in vivo. We show that Deiters' cells function as phagocytes. Upon trauma,
      their phalangeal processes swell and the resulting close cellular contacts allow
      engulfment of apoptotic cell debris. Apical domains of dying hair cells are
      eliminated from the inner ear sensory epithelia, an event thought to depend on
      supporting cells' actomyosin contractile activity. We show that in the case of
      apoptotic outer hair cells of the organ of Corti, elimination of their apices is
      preceded by strong cell body shrinkage, emphasizing the role of the dying cell
      itself in the cleavage. Our data reveal that the resealing of epithelial surface
      by junctional extensions of Deiters' cells is dynamically reinforced by newly
      polymerized F-actin belts. By analyzing Cdc42-inactivated Deiters' cells with
      defects in actin dynamics and surface closure, we show that compromised barrier
      integrity shifts hair cell death from apoptosis to necrosis and leads to expanded
      hair cell and nerve fiber damage. Our results have implications concerning
      therapeutic protective and regenerative interventions, because both interventions
      should maintain barrier integrity. 

PMID- 25074371
TI  - Impact of time of presentation on process performance and outcomes in ST-segment
      elevation myocardial infarction: a report from the American Heart Association:
      Mission Lifeline program.
AB  - BACKGROUND: Prior studies demonstrated that patients with ST-segment-elevation
      myocardial infarction presenting during off-hours (weeknights, weekends, and
      holidays) have slower reperfusion times. Recent nationwide initiatives have
      emphasized 24/7 quality care in ST-segment-elevation myocardial infarction. It
      remains unclear whether patients presenting off-hours versus on-hours receive
      similar quality care in contemporary practice. METHODS AND RESULTS: Using Acute
      Coronary Treatment and Intervention Outcomes Network-Get With The Guidelines
      (ACTION-GWTG) database, we examined ST-segment-elevation myocardial infarction
      performance measures in patients presenting off-hours (n=27 270) versus on-hours
      (n=15 972; January 2007 to September 2010) at 447 US centers. Key quality
      measures assessed were aspirin use within first 24 hours, door-to-balloon time,
      door-to-ECG time, and door-to-needle time. In-hospital risk-adjusted all-cause
      mortality was calculated. Baseline demographic and clinical characteristics were
      similar. Aspirin use within 24 hours approached 99% in both groups. Among
      patients undergoing primary percutaneous coronary intervention (n=41 979; 97.1%),
      median door-to-balloon times were 56 versus 72 minutes (P<0.0001) for on-hours
      versus off-hours. The proportion of patients achieving door-to-balloon time <=90
      minutes was 87.8% versus 79.2% (P<0.0001), respectively. There were no
      differences attaining door-to-ECG time <=10 minutes (73.4% versus 74.3%, P=0.09)
      and door-to-needle time <=30 minutes (62.3% versus 58.7%; P=0.44) between on
      hours versus off-hours. Although in-hospital all-cause mortality was similar
      (4.2%) in both groups, the risk-adjusted all-cause mortality was higher for
      patients presenting off-hours (odds ratio, 1.13; 95% confidence interval, 1.02
      1.26). CONCLUSIONS: In contemporary community practice, achievement of quality
      performance measures in patients presenting with ST-segment-elevation myocardial
      infarction was high, regardless of time of presentation. Door-to-balloon time
      was, however, slightly delayed (by an average of 16 minutes), and risk-adjusted
      in-hospital mortality was 13% higher in patients presenting off-hours.

PMID- 25074373
TI  - Interplay between time of presentation, timeliness of reperfusion, and outcome
      after ST-segment-elevation myocardial infarction.

PMID- 25074372
TI  - Reducing contrast-induced acute kidney injury using a regional multicenter
      quality improvement intervention.
AB  - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is associated with
      increased morbidity and mortality after percutaneous coronary interventions and
      is a patient safety objective of the National Quality Forum. However, no formal
      quality improvement program to prevent CI-AKI has been conducted. Therefore, we
      sought to determine whether a 6-year regional multicenter quality improvement
      intervention could reduce CI-AKI after percutaneous coronary interventions.
      METHODS AND RESULTS: We conducted a prospective multicenter quality improvement
      study to prevent CI-AKI (serum creatinine increase >=0.3 mg/dL within 48 hours or
      >=50% during hospitalization) among 21 067 nonemergent patients undergoing
      percutaneous coronary interventions at 10 hospitals between 2007 and 2012. Six
      intervention hospitals participated in the quality improvement intervention. Two
      hospitals with significantly lower baseline rates of CI-AKI, which served as
      benchmark sites and were used to develop the intervention, and 2 hospitals not
      receiving the intervention were used as controls. Using time series analysis and
      multilevel poisson regression clustering to the hospital level, we calculated
      adjusted risk ratios for CI-AKI comparing the intervention period to baseline.
      Adjusted rates of CI-AKI were significantly reduced in hospitals receiving the
      intervention by 21% (risk ratio, 0.79; 95% confidence interval: 0.67-0.93;
      P=0.005) for all patients and by 28% in patients with baseline estimated
      glomerular filtration rate <60 mL/min per 1.73 m(2) (risk ratio, 0.72; 95%
      confidence interval: 0.56-0.91; P=0.007). Benchmark hospitals had no significant
      changes in CI-AKI. Key qualitative system factors associated with improvement
      included multidisciplinary teams, limiting contrast volume, standardized fluid
      orders, intravenous fluid bolus, and patient education about oral hydration.
      CONCLUSIONS: Simple cost-effective quality improvement interventions can prevent
      <=1 in 5 CI-AKI events in patients with undergoing nonemergent percutaneous
      coronary interventions.

PMID- 25074374
TI  - Desert dust is a risk factor for the incidence of acute myocardial infarction in
      Western Japan.
AB  - BACKGROUND: Recently, there has been increasing concern about adverse health
      effects of exposure to desert dust events. However, the association between dust
      and the incidence of ischemic heart diseases is unknown. The aim of the present
      study was to elucidate whether Asian dust (AD), a windblown sand dust originating
      from mineral soil in China and Mongolia, is associated with the incidence of
      acute myocardial infarction (AMI). METHODS AND RESULTS: We investigated the data
      regarding hospitalization because of AMI among 3068 consecutive patients from 4
      AMI centers in Fukuoka, Japan, and data for AD from April 2003 to December 2010.
      We applied a time-stratified case-crossover design to examine the association
      between AD and the incidence of AMI. Using a conditional logistic regression
      analysis, we estimated the odds ratios of AMI associated with AD after
      controlling for ambient temperature and relative humidity. The occurrence of AD
      events 0 to 4 days before the day of admission was significantly associated with
      the incidence of AMI. In particular, the occurrence of AD 4 days before admission
      was significantly associated with the onset of AMI. CONCLUSIONS: These data
      suggest that exposure to AD a few days before symptom onset is associated with
      the incidence of AMI.

PMID- 25074375
TI  - Place of residence and outcomes of patients with heart failure: analysis from the
      telemonitoring to improve heart failure outcomes trial.
AB  - BACKGROUND: Recent studies show an association between neighborhood-level
      measures of socioeconomic status (SES) and outcomes for patients with heart
      failure. We do not know whether neighborhood SES has a primary effect or is a
      marker for individual SES. METHODS AND RESULTS: We used the data from
      participants of the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF)
      trial, recruited from 33 US internal medicine and cardiology practices and
      examined the association between neighborhood SES and outcomes of patients with
      heart failure. We used census tracts as proxies for neighborhoods and constructed
      summary SES scores that included information about wealth and income, education,
      and occupation. The primary end points were readmission and all-cause mortality
      at 6 months. We conducted patient interviews and medical chart reviews to obtain
      demographic information, clinical factors, therapies, and individual SES. We
      included 1557 patients: 524, 516, and 517 from low, medium, and high SES
      neighborhoods, respectively (mean age, 61.1+/-15.2 years; 42.2% women).Overall,
      745 patients (47.8%) had >=1 readmission and 179 patients (11.5%) died. When
      compared with patients in high SES neighborhoods, those living in low-SES
      neighborhoods were more likely to be readmitted (odds ratio, 1.35; 95% confidence
      interval, 1.01-1.82), but the mortality rates were not significantly different
      (odds ratio, 0.78; 95% confidence interval, 0.50-1.18). The results were
      consistent after multivariable adjustments for individual demographics, clinical
      factors, and individual SES. CONCLUSIONS: Among patients with heart failure,
      neighborhood SES was significantly associated with 6-month all-cause readmission
      even after adjusting for other patient-level factors, including individual SES.
      Greater number of events and longer follow-up is required to ascertain the
      potential effect of neighborhood SES on mortality. CLINICAL TRIAL REGISTRATION
      URL: http://clinicaltrials.gov/. Unique identifier: NCT00303212.

PMID- 25074376
TI  - Diversity and recombination of human parechovirus in children with acute
      gastroenteritis in Guangzhou, China.
AB  - Human parechovirus (HPeV), a member of Picornaviridae family, is a widespread
      pathogen causing a wide spectrum of diseases. Like other picornaviruses, HPeV
      genome recombination has been detected. A total of 322 fecal samples were
      collected from children outpatients in Guangzhou, China, including 42 (13.0%,
      42/322) HPeV-positive samples detected in most of the infected children less than
      two years old. Seven HPeV genotypes (HPeV1, HPeV3, HPeV4, HPeV5, HPeV6, HPeV8 and
      HPeV14) were detected, among which, HPeV14, a rare genotype, was reported for the
      first time in children with acute gastroenteritis in China. This study revealed
      recombination events in eight samples. Clinical profiles did not yield
      statistical significance between children with HPeV infection alone and cases
      without pathogens detected. In conclusion, this study demonstrated that HPeV
      circulated in Guangzhou, China is diverse genetically, which provided evidence of
      recombination in HPeV in China.

PMID- 25074377
TI  - Broad-host-range vector system for synthetic biology and biotechnology in
      cyanobacteria.
AB  - Inspired by the developments of synthetic biology and the need for improved
      genetic tools to exploit cyanobacteria for the production of renewable
      bioproducts, we developed a versatile platform for the construction of broad-host
      range vector systems. This platform includes the following features: (i) an
      efficient assembly strategy in which modules released from 3 to 4 donor plasmids
      or produced by polymerase chain reaction are assembled by isothermal assembly
      guided by short GC-rich overlap sequences. (ii) A growing library of molecular
      devices categorized in three major groups: (a) replication and chromosomal
      integration; (b) antibiotic resistance; (c) functional modules. These modules can
      be assembled in different combinations to construct a variety of autonomously
      replicating plasmids and suicide plasmids for gene knockout and knockin. (iii) A
      web service, the CYANO-VECTOR assembly portal, which was built to organize the
      various modules, facilitate the in silico construction of plasmids, and encourage
      the use of this system. This work also resulted in the construction of an
      improved broad-host-range replicon derived from RSF1010, which replicates in
      several phylogenetically distinct strains including a new experimental model
      strain Synechocystis sp. WHSyn, and the characterization of nine antibiotic
      cassettes, four reporter genes, four promoters, and a ribozyme-based insulator in
      several diverse cyanobacterial strains. 

PMID- 25074378
TI  - The telomeric protein Pot1 from Schizosaccharomyces pombe binds ssDNA in two
      modes with differing 3' end availability.
AB  - Telomere protection and length regulation are important processes for aging,
      cancer and several other diseases. At the heart of these processes lies the
      single-stranded DNA (ssDNA)-binding protein Pot1, a component of the telomere
      maintenance complex shelterin, which is present in species ranging from fission
      yeast to humans. Pot1 contains a dual OB-fold DNA-binding domain (DBD) that fully
      confers its high affinity for telomeric ssDNA. Studies of S. pombe Pot1-DBD and
      its individual OB-fold domains revealed a complex non-additive behavior of the
      two OB-folds in the context of the complete Pot1 protein. This behavior includes
      the use of multiple distinct binding modes and an ability to form higher order
      complexes. Here we use NMR and biochemical techniques to investigate the
      structural features of the complete Pot1-DBD. These experiments reveal one
      binding mode characterized by only subtle alternations to the individual OB-fold
      subdomain structures, resulting in an inaccessible 3' end of the ssDNA. The
      second binding mode, which has equivalent affinity, interacts differently with
      the 3' end, rendering it available for interaction with other proteins. These
      findings suggest a structural switch that contributes to telomere end-protection
      and length regulation. 

PMID- 25074379
TI  - CRISPR-Cas9-assisted recombineering in Lactobacillus reuteri.
AB  - Clustered regularly interspaced palindromic repeats (CRISPRs) and the CRISPR
      associated (Cas) nuclease protect bacteria and archeae from foreign DNA by site
      specific cleavage of incoming DNA. Type-II CRISPR-Cas systems, such as the
      Streptococcus pyogenes CRISPR-Cas9 system, can be adapted such that Cas9 can be
      guided to a user-defined site in the chromosome to introduce double-stranded
      breaks. Here we have developed and optimized CRISPR-Cas9 function in the lactic
      acid bacterium Lactobacillus reuteri ATCC PTA 6475. We established proof-of
      concept showing that CRISPR-Cas9 selection combined with single-stranded DNA
      (ssDNA) recombineering is a realistic approach to identify at high efficiencies
      edited cells in a lactic acid bacterium. We show for three independent targets
      that subtle changes in the bacterial genome can be recovered at efficiencies
      ranging from 90 to 100%. By combining CRISPR-Cas9 and recombineering, we
      successfully applied codon saturation mutagenesis in the L. reuteri chromosome.
      Also, CRISPR-Cas9 selection is critical to identify low-efficiency events such as
      oligonucleotide-mediated chromosome deletions. This also means that CRISPR-Cas9
      selection will allow identification of recombinant cells in bacteria with low
      recombineering efficiencies, eliminating the need for ssDNA recombineering
      optimization procedures. We envision that CRISPR-Cas genome editing has the
      potential to change the landscape of genome editing in lactic acid bacteria, and
      other Gram-positive bacteria. 

PMID- 25074380
TI  - Identification of discrete classes of small nucleolar RNA featuring different
      ends and RNA binding protein dependency.
AB  - Small nucleolar RNAs (snoRNAs) are among the first discovered and most
      extensively studied group of small non-coding RNA. However, most studies focused
      on a small subset of snoRNAs that guide the modification of ribosomal RNA. In
      this study, we annotated the expression pattern of all box C/D snoRNAs in normal
      and cancer cell lines independent of their functions. The results indicate that
      C/D snoRNAs are expressed as two distinct forms differing in their ends with
      respect to boxes C and D and in their terminal stem length. Both forms are
      overexpressed in cancer cell lines but display a conserved end distribution.
      Surprisingly, the long forms are more dependent than the short forms on the
      expression of the core snoRNP protein NOP58, thought to be essential for C/D
      snoRNA production. In contrast, a subset of short forms are dependent on the
      splicing factor RBFOX2. Analysis of the potential secondary structure of both
      forms indicates that the k-turn motif required for binding of NOP58 is less
      stable in short forms which are thus less likely to mature into a canonical
      snoRNP. Taken together the data suggest that C/D snoRNAs are divided into at
      least two groups with distinct maturation and functional preferences. 

PMID- 25074382
TI  - Major alteration in coxsackievirus B3 genomic RNA structure distinguishes a
      virulent strain from an avirulent strain.
AB  - Coxsackievirus B3 (CV-B3) is a cardiovirulent enterovirus that utilizes a 5'
      untranslated region (5'UTR) to complete critical viral processes. Here, we
      directly compared the structure of a 5'UTR from a virulent strain with that of a
      naturally occurring avirulent strain. Using chemical probing analysis, we
      identified a structural difference between the two 5'UTRs in the highly
      substituted stem-loop II region (SLII). For the remainder of the 5'UTR, we
      observed conserved structure. Comparative sequence analysis of 170 closely
      related enteroviruses revealed that the SLII region lacks conservation. To
      investigate independent folding and function, two chimeric CV-B3 strains were
      created by exchanging nucleotides 104-184 and repeating the 5'UTR structural
      analysis. Neither the parent SLII nor the remaining domains of the background
      5'UTR were structurally altered by the exchange, supporting an independent
      mechanism of folding and function. We show that the attenuated 5'UTR lacks
      structure in the SLII cardiovirulence determinant. 

PMID- 25074381
TI  - 3'LIFE: a functional assay to detect miRNA targets in high-throughput.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene output at the
      post-transcriptional level by targeting degenerate elements primarily in
      3'untranslated regions (3'UTRs) of mRNAs. Individual miRNAs can regulate networks
      of hundreds of genes, yet for the majority of miRNAs few, if any, targets are
      known. Misexpression of miRNAs is also a major contributor to cancer progression,
      thus there is a critical need to validate miRNA targets in high-throughput to
      understand miRNAs' contribution to tumorigenesis. Here we introduce a novel high
      throughput assay to detect miRNA targets in 3'UTRs, called Luminescent
      Identification of Functional Elements in 3'UTRs (3'LIFE). We demonstrate the
      feasibility of 3'LIFE using a data set of 275 human 3'UTRs and two cancer
      relevant miRNAs, let-7c and miR-10b, and compare our results to alternative
      methods to detect miRNA targets throughout the genome. We identify a large number
      of novel gene targets for these miRNAs, with only 32% of hits being
      bioinformatically predicted and 27% directed by non-canonical interactions.
      Functional analysis of target genes reveals consistent roles for each miRNA as
      either a tumor suppressor (let-7c) or oncogenic miRNA (miR-10b), and
      preferentially target multiple genes within regulatory networks, suggesting
      3'LIFE is a rapid and sensitive method to detect miRNA targets in high
      throughput. 

PMID- 25074385
TI  - Electroacupuncture inhibits excessive interferon-gamma evoked up-regulation of
      P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain.
AB  - BACKGROUND: Although electroacupuncture (EA) is effective in the relief of
      neuropathic pain, the underlying mechanisms remain unclear. Previous studies have
      reported immunomodulatory effects of EA in rats. Since excessive release of
      interferon-gamma (IFN-gamma) after nerve injury transforms quiescent spinal
      microglia into an activated state with more neuropathic pain, associated with
      purinergic receptor P2X4 expression, it is possible that EA may mediate its
      analgesic effect by attenuating IFN-gamma release and subsequent generation of
      P2X4R(+) microglia. METHODS: Male rats underwent chronic constriction injury
      (CCI) or IFN-gamma intrathecal injection and von Frey tests were performed to
      evaluate the effect of EA on pain thresholds. Spinal IFN-gamma and P2X4R
      expression levels were measured by immunohistochemistry, real-time PCR, enzyme
      immunoassay, and/or western blots. In vitro primary cultures of microglia were
      used to examine IFN-gamma activation of P2X4R(+) cells. RESULTS: In CCI rats, EA
      treatment significantly increased paw withdrawal threshold relative to control.
      IFN-gamma facilitated P2X4R(+) microglia activation both in vitro and in vivo. EA
      also down-regulated both P2X4R and IFN-gamma expression in the spinal cord after
      CCI. However, EA did not exert the same analgesic effect after intrathecal IFN
      gamma injection. CONCLUSIONS: EA ameliorated tactile allodynia after peripheral
      nerve injury by down-regulating excessive expression of IFN-gamma in the spinal
      cord and subsequently reducing expression of P2X4R.

PMID- 25074383
TI  - The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2'
      deoxycytidine lesions.
AB  - Decitabine (5-aza-2'-deoxycytidine, 5-azadC) is used in the treatment of
      Myelodysplatic syndrome (MDS) and Acute Myeloid Leukemia (AML). Its mechanism of
      action is thought to involve reactivation of genes implicated in differentiation
      and transformation, as well as induction of DNA damage by trapping DNA
      methyltranferases (DNMT) to DNA. We demonstrate for the first time that base
      excision repair (BER) recognizes 5-azadC-induced lesions in DNA and mediates
      repair. We find that BER (XRCC1) deficient cells are sensitive to 5-azadC and
      display an increased amount of DNA single- and double-strand breaks. The XRCC1
      protein co-localizes with DNMT1 foci after 5-azadC treatment, suggesting a novel
      and specific role of XRCC1 in the repair of trapped DNMT1. 5-azadC-induced DNMT
      foci persist in XRCC1 defective cells, demonstrating a role for XRCC1 in repair
      of 5-azadC-induced DNA lesions. Poly (ADP-ribose) polymerase (PARP) inhibition
      prevents XRCC1 relocation to DNA damage sites, disrupts XRCC1-DNMT1 co
      localization and thereby efficient BER. In a panel of AML cell lines, combining 5
      azadC and Olaparib cause synthetic lethality. These data suggest that PARP
      inhibitors can be used in combination with 5-azadC to improve treatment of MDS
      and AML. 

PMID- 25074384
TI  - Inhibition of the intestinal sodium-coupled glucose transporter 1 (SGLT1) by
      extracts and polyphenols from apple reduces postprandial blood glucose levels in
      mice and humans.
AB  - SCOPE: There is a growing interest in food constituents that could reduce
      intestinal glucose absorption to prevent overshooting plasma glucose and insulin
      levels in patients with prediabetes and diabetes mellitus type 2. METHODS AND
      RESULTS: We here demonstrate that an extract and individual polyphenols from
      apple diminish sodium-coupled glucose transporter 1 (SGLT1) mediated glucose
      uptake in vitro and in vivo. Inhibition of transport of sugars by SGLT1 was shown
      in Xenopus oocytes and in mice jejunal segments. Strongest inhibition was
      observed for phlorizin with IC50 values for transport inhibition of 0.46 +/- 0.19
      and 4.1 +/- 0.6 MUM in oocytes and intestinal segments, respectively. An oral
      glucose tolerance test performed in volunteers with prior administration of the
      apple extract reduced venous blood glucose and plasma insulin levels, similar to
      findings obtained in C57BL/6N mice. Analysis of human urine samples revealed that
      the extract increased modestly renal glucose loss that is most likely a result of
      inhibition of renal glucose reabsorption by phloretin derivatives found in plasma
      of the volunteers. CONCLUSION: Although the apple extract substantially decreased
      intestinal glucose absorption in all test systems, the finding that there are
      systemic effects that relate to inhibition of glucose transport processes beyond
      the intestine addresses safety issues that need further exploitation.

PMID- 25074386
TI  - Association between the body mass index and the risk of Barrett's esophagus in
      Japan.
AB  - BACKGROUND: We investigated the association between long-segment Barrett's
      esophagus and obesity in the Japanese population in a multicenter case-control
      trial. METHODS: One hundred thirteen patients with endoscopically detected
      Barrett's esophagus with a length of more than 2 cm and the same number of sex-
      and age-matched controls were prospectively enrolled. Barrett's esophagus was
      diagnosed based on the Prague C and M criteria. The body mass index (BMI) of the
      subjects was categorized into the following groups: normal, BMI <22.9;
      overweight, BMI 23.0-24.9, and obese, BMI >25.0. To determine the association
      between BMI and the risk of Barrett's esophagus, multivariate logistic regression
      analyses were performed. RESULTS: The basically adjusted regression model
      adjusted for smoking and alcohol consumption revealed that overweight and obesity
      were significantly associated with an elevated risk of Barrett's esophagus (OR
      2.4, 95% CI 1.2-4.7, and OR 2.5, 95% CI 1.3-4.6, respectively). The intensity of
      the association was not attenuated even after adjustment for gastroesophageal
      reflux disease-related parameters. CONCLUSIONS: An increased BMI was associated
      with an increased risk for Barrett's esophagus through a gastroesophageal reflux
      independent mechanism in the Japanese population. Further, unlike in Caucasian
      populations, being even slightly overweight with a BMI of 23.0-24.9 was an
      independent risk factor in the Japanese population.

PMID- 25074388
TI  - Response to: Is inverted BMI really better than BMI in predicting body fatness in
      children?

PMID- 25074387
TI  - Impact of medium and long chain triglycerides consumption on appetite and food
      intake in overweight men.
AB  - BACKGROUND: Medium chain triglycerides (MCT) enhance thermogenesis and may reduce
      food intake relative to long chain triglycerides (LCT). The goal of this study
      was to establish the effects of MCT on appetite and food intake and determine
      whether differences were due to differences in hormone concentrations. METHODS:
      Two randomized, crossover studies were conducted in which overweight men consumed
      20 g of MCT or corn oil (LCT) at breakfast. Blood samples were obtained over 3 h.
      In Study 1 (n=10), an ad lib lunch was served after 3 h. In Study 2 (n=7), a
      preload containing 10 g of test oil was given at 3 h and lunch was served 1 h
      later. Linear mixed model analyses were performed to determine the effects of MCT
      and LCT oil on change in hormones and metabolites from fasting, adjusting for
      body weight. Correlations were computed between differences in hormones just
      before the test meals and differences in intakes after the two oils for Study 1
      only. RESULTS: Food intake at the lunch test meal after the MCT preload (Study 2)
      was (mean+/-s.e.m.) 532+/-389 kcal vs 804+/-486 kcal after LCT (P<0.05). MCT
      consumption resulted in a lower rise in triglycerides (P=0.014) and glucose
      (P=0.066) and a higher rise in peptide YY (PYY, P=0.017) and leptin (P=0.036)
      compared with LCT (combined data). Correlations between differences in hormone
      levels (glucagon-like peptide (GLP-1), PYY) and differences in food intake were
      in the opposite direction to expectations. CONCLUSIONS: MCT consumption reduced
      food intake acutely but this does not seem to be mediated by changes in GLP-1,
      PYY and insulin.

PMID- 25074389
TI  - Associations between weight status and liking scores for sweet, salt and fat
      according to the gender in adults (The Nutrinet-Sante study).
AB  - BACKGROUND/OBJECTIVES: As taste preferences may be associated with obesity, the
      present study investigated whether obese subjects presented heightened liking for
      the sensations of sweet, salt and fat. SUBJECTS/METHODS: Liking scores were
      determined by a questionnaire including 83 items on liking for sweet or fatty
      foods, and the preferred extent of seasoning with salt, sweet or fat. Data from
      46909 adults included in the French web-based observational cohort of the
      Nutrinet-Sante study were collected and weighted according to the national
      population census. Relationships between liking scores and body mass index (BMI)
      as categorical or linear explanatory variable were assessed separately by gender
      using covariance and linear regression analyses, adjusted for age, education
      level, living area, smoking and alcohol. RESULTS: Overall liking scores for salt
      and fat were linearly positively linked to BMI in men and women (P<=0.001) and
      were higher in obese than in normal-weight individuals. The score difference
      between BMI categories was greater in women for fat liking only. For sweet
      liking, results differed between gender and compounding factors. Liking for added
      sugar and sweet foods was positively linked to BMI in women unlike in men; liking
      for natural sweetness was negatively linked to BMI in both genders. CONCLUSIONS:
      This study demonstrates that the relationship between liking and BMI differs
      according to the gender in its magnitude for fat and in its nature for sweet,
      unlike that for salt. Liking for sweet and fat may be linked to overconsumption
      of the corresponding foods, especially in women. This warrants further
      investigation.

PMID- 25074390
TI  - Body size dissatisfaction among young adults from the 1982 Pelotas birth cohort.
AB  - BACKGROUND/OBJECTIVES: To identify the prevalence and factors associated with
      body dissatisfaction. SUBJECTS/METHODS: Birth cohort study investigating 4100
      subjects (2187 men and 1913 women) aged between 22 and 23 years who answered
      questionnaires, including the body satisfaction Stunkard Scale were included in
      the study; they were weighed and measured. Multinomial logistic regression was
      used in the crude and adjusted analyses. RESULTS: The prevalence of body
      dissatisfaction was 64% (95% CI, 62.7-65.6); 42% (95% CI, 40.6-43.6) of the
      subjects reported feeling larger than the desired body size, and 22% (95% CI,
      20.7-23.3) reported feeling smaller than desired. Underweight subjects, subjects
      with less schooling, poor and sedentary male subjects with low psychological well
      being and female subjects who were already mothers were more likely to express
      body dissatisfaction, perceiving their body as smaller than the desirable body
      size. The prevalence of body dissatisfaction was also high among overweight
      subjects, subjects with a high socioeconomic status and married female subjects,
      who perceived their body size as too large. Minor psychiatric disorders were
      associated with body dissatisfaction in all subjects, regardless of perceiving
      themselves as larger or smaller than the desired body size. Most women perceived
      themselves as larger, but similar proportions of men perceived themselves as too
      small or too large. CONCLUSIONS: Body dissatisfaction was observed among men and
      women with normal weight, but it was more evident in the obese individuals.
      Regardless of the nutritional status, both men and women should be appropriately
      counseled because body size perception can lead to unhealthy behaviors in
      relation to diet and physical activity.

PMID- 25074391
TI  - Correlation of serum adiponectin and adiponectin gene polymorphism with metabolic
      syndrome in Chinese adolescents.
AB  - BACKGROUND/OBJECTIVES: To investigate the association of adiponectin and its gene
      polymorphisms with metabolic syndrome (MetS) and cardiovascular disease (CVD)
      risk factors in Chinese adolescents. SUBJECTS/METHODS: This cross-sectional study
      enrolled 919 healthy middle school students (aged 11-16 years; 46.7% females).
      All participants underwent anthropometric and biochemical examinations, and MetS
      was diagnosed using 2007 International Diabetes Federation criteria. The presence
      of adiponectin and its genotypes of single nucleotide polymorphisms (SNPs)
      rs266729 (-11377C/G), rs2241766 (+45T/G) and rs1501299 (+276G/T) was detected.
      RESULTS: (1) Serum adiponectin levels were negatively correlated with numerous
      CVD risk factors (all P<0.05), and following adjustments for confounding factors,
      a lower adiponectin level was an independent risk factor for MetS (odds
      ratio=5.59; 95% confidence interval: 1.90, 16.41). Central obesity and low levels
      of high-density lipoprotein cholesterol were positively associated with MetS and
      reduced serum adiponectin levels. (2) The genotype and frequencies of SNP-11377
      and SNP+276 in a MetS group and non-MetS group were not significantly different.
      Subjects with genotype SNP+45 GG were at higher risk for MetS compared with
      subjects with genotypes SNP+45 TT (P=0.033) or TT+TG (P=0.021). Subjects with
      genotype SNP+276 TT or TT+TG had higher levels of serum adiponectin compared with
      subjects with SNP+276 GG (P=0.012 and 0.014, respectively). CONCLUSIONS:
      Adiponectin may be used as a predictive biomarker of MetS, and shows a
      significant association with CVD risk factors in Chinese adolescents. Adiponectin
      gene polymorphisms are associated with serum adiponectin concentrations and the
      presence of MetS.

PMID- 25074393
TI  - Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV
      seropositive individuals.
AB  - OBJECTIVES: To propose objective ratios using anthropometry and dual-energy X-ray
      absorptiometry (DXA) and to suggest cutoff points for them in order to classify
      lipodystrophy in male patients. METHODS: It is a cross-sectional study. DXA was
      applied and anthropometric measurements were performed in 100 men on highly
      active antiretroviral therapy. Receiver operating characteristic curves were used
      to propose cutoffs. Individuals were divided in without (lipo-) or with (lipo+)
      lipodystrophy and their metabolic parameters were compared. RESULTS: The
      following ratios were proposed: fat mass ratio by DXA (FMR), waist thigh ratio
      (WTR), waist calf ratio (WCR), and arm to trunk ratio (ATR). The best cutoffs
      observed for FMR, WTR and ATR were 1.26, 1.74 and 2.08, respectively. Using the
      proposed cutoff for FMR, we observed worse metabolic profile, with increased
      tryglicerides, fasting serum glucose and more hypercholesterolemia in the lipo+
      group. WTR and ATR showed a significant correlation with FMR. CONCLUSIONS:
      Anthropometric ratios (WTR/ATR) and FMR can be used to aid the diagnosis of
      lipodystrophy in order to contribute to a more accurate and earlier diagnosis
      permitting intervention and even preventing metabolic disturbances.

PMID- 25074392
TI  - The anti-obesity effects of green tea in human intervention and basic molecular
      studies.
AB  - Many researchers have reported that obesity is a major risk factor for diabetes,
      cardiovascular diseases, several forms of cancer (such as breast, colon and
      prostate), pulmonary, osteoarticular and metabolic diseases in the past decades.
      Recently, the hypolipidemic and anti-obesity effects of green tea in animals and
      humans have slowly become a hot topic in nutritional and food science research.
      This review will up-date the information of the anti-obesity effects of green tea
      in human intervention and animal studies. During recent years, an increasing
      number of clinical trials have confirmed the beneficial effects of green tea on
      obesity. However, the optimal dose has not yet been established owing to the very
      different results from studies with a similar design, which may be caused by
      differences in the extent of obesity, dietary intake, physical activity
      intensity, the strength of subjects' compliance to test instruction, the genetic
      background of populations, body composition and dietary habits. Therefore,
      further investigations on a larger scale and with longer periods of observation
      and tighter controls are needed to define optimal doses in subjects with varying
      degrees of metabolic risk factors and to determine differences in beneficial
      effects among diverse populations. Moreover, data from laboratory studies have
      shown that green tea has important roles in fat metabolism by reducing food
      intake, interrupting lipid emulsification and absorption, suppressing
      adipogenesis and lipid synthesis and increasing energy expenditure via
      thermogenesis, fat oxidation and fecal lipid excretion. However, the exact
      molecular mechanisms remain elusive. 

PMID- 25074394
TI  - Hair-sparing whole brain radiotherapy with volumetric arc therapy in patients
      treated for brain metastases: dosimetric and clinical results of a phase II
      trial.
AB  - PURPOSE: To report the dosimetric results and impact of volumetric arc therapy
      (VMAT) on temporary alopecia and hair-loss related quality of life (QOL) in whole
      brain radiotherapy (WBRT). METHODS: The potential of VMAT-WBRT to reduce the dose
      to the hair follicles was assessed. A human cadaver was treated with both VMAT
      WBRT and conventional opposed field (OF) WBRT, while the subcutaneously absorbed
      dose was measured by radiochromic films and calculated by the planning system.
      The impact of these dose reductions on temporary alopecia was examined in a
      prospective phase II trial, with the mean score of hair loss at 1 month after
      VMAT-WBRT (EORTC-QOL BN20) as a primary endpoint and delivering a dose of 20 Gy
      in 5 fractions. An interim analysis was planned after including 10 patients to
      rule out futility, defined as a mean score of hair loss exceeding 56.7. A
      secondary endpoint was the global alopecia areata severity score measured with
      the "Severity of Alopecia Tool" (SALT) with a scale of 0 (no hair loss) to 100
      (complete alopecia). RESULTS: For VMAT-WBRT, the cadaver measurements
      demonstrated a dose reduction to the hair follicle volume of 20.5% on average and
      of 41.8% on the frontal-vertex-occipital medial axis as compared to OF-WBRT. In
      the phase II trial, a total of 10 patients were included before the trial was
      halted due to futility. The EORTC BN20 hair loss score following WBRT was 95 (SD
      12.6). The average median dose to the hair follicle volume was 12.6 Gy (SD 0.9),
      corresponding to a 37% dose reduction compared to the prescribed dose. This
      resulted in a mean SALT-score of 75. CONCLUSIONS: Compared to OF-WBRT, VMAT-WBRT
      substantially reduces hair follicle dose. These dose reductions could not be
      related to an improved QOL or SALT score.

PMID- 25074395
TI  - Prestimulus theta in the human hippocampus predicts subsequent recognition but
      not recall.
AB  - Human theta (4-8 Hz) activity in the medial temporal lobe correlates with memory
      formation; however, the precise role that theta plays in the memory system
      remains elusive (Hanslmayr and Staudigl, ). Recently, prestimulus theta activity
      has been associated with successful memory formation, although its specific
      cognitive role remains unknown (e.g., Fell et al., 2011). In this report, we
      demonstrate that prestimulus theta in the hippocampus indexes encoding that
      supports old-new recognition memory but not recall. These findings suggest that
      human hippocampal prestimulus theta may preferentially participate in the
      encoding of item information, as opposed to associative information.

PMID- 25074397
TI  - Early progressive strength training to enhance recovery after fast-track total
      knee arthroplasty: a randomized controlled trial.
AB  - OBJECTIVE: To compare 7 weeks of supervised physical rehabilitation with or
      without progressive strength training (PST) commenced early after fast-track
      total knee arthroplasty (TKA) on functional performance. METHODS: In total, 82
      patients with a unilateral primary TKA were randomized to 2 different
      interventions: 7 weeks of supervised physical rehabilitation with PST (PST group)
      and without PST (CON group) commenced early after fast-track TKA. The primary
      outcome was the maximal distance walked in 6 minutes (6-minute walk test).
      Secondary outcomes were lower extremity strength and power, knee joint effusion
      and range of motion, knee pain, and self-reported disability and quality of life.
      All outcome measures were assessed before TKA (baseline) and 4, 8, and 26 weeks
      after TKA. RESULTS: There was no statistically significant difference between the
      PST and CON groups in the change score from baseline to the 8-week postoperative
      assessment (primary end point) for the 6-minute walk test with unadjusted
      baseline scores (mean difference between groups: -11.3 meters [95% confidence
      interval -45.4, 22.7]; analysis of variance P = 0.51). There were no
      statistically significant or clinically meaningful differences between groups in
      change scores from baseline to any other time point for all secondary outcomes.
      The secondary outcome knee extension strength did not reach the level recorded
      before surgery in both groups. CONCLUSION: Seven weeks of supervised physical
      rehabilitation with PST was not superior to 7 weeks of supervised physical
      rehabilitation without PST in improving functional performance, measured as the
      maximal walking distance in 6 minutes, at the primary end point 8 weeks after
      fast-track TKA.

PMID- 25074396
TI  - A randomized study of contingency management and spirometric lung age for
      motivating smoking cessation among injection drug users.
AB  - BACKGROUND: Even after quitting illicit drugs, tobacco abuse remains a major
      cause of morbidity and mortality in former injection drug users. An important
      unmet need in this population is to have effective interventions that can be used
      in the context of community based care. Contingency management, where a patient
      receives a monetary incentive for healthy behavior choices, and incorporation of
      individual counseling regarding spirometric "lung age" (the age of an average
      healthy individual with similar spirometry) have been shown to improve cessation
      rates in some populations. The efficacy of these interventions on improving
      smoking cessation rates has not been studied among current and former injection
      drug users. METHODS: In a randomized, factorial design study, we recruited 100
      active smokers from an ongoing cohort study of current and former injection drug
      users to assess the impact of contingency management and spirometric lung age on
      smoking cessation. The primary outcome was 6-month biologically-confirmed smoking
      cessation comparing contingency management, spirometric lung age or both to usual
      care. Secondary outcomes included differences in self-reported and biologically
      confirmed cessation at interim visits, number of visits attended and quit
      attempts, smoking rates at interim visits, and changes in Fagerstrom score and
      self-efficacy. RESULTS: Six-month biologically-confirmed smoking cessations rates
      were 4% usual care, 0% lung age, 14% contingency management and 0% for combined
      lung age and contingency management (p = 0.13). There were no differences in
      secondary endpoints comparing the four interventions or when pooling the lung age
      groups. Comparing contingency management to non-contingency management, 6-month
      cessation rates were not different (7% vs. 2%; p = 0.36), but total number of
      visits with exhaled carbon monoxide-confirmed abstinence were higher for
      contingency management than non-contingency management participants (0.38 vs.
      0.06; p = 0.03), and more contingency management participants showed reduction in
      their Fagerstrom score from baseline to follow-up (39% vs. 18%; p = 0.03).
      CONCLUSIONS: While lung age appeared ineffective, contingency management was
      associated with more short-term abstinence and lowered nicotine addiction.
      Contingency management may be a useful tool in development of effective tobacco
      cessation strategies among current and former injection drug users. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01334736 (April 12, 2011).

PMID- 25074398
TI  - Fluorescent TEM-1 beta-lactamase with wild-type activity as a rapid drug sensor
      for in vitro drug screening.
AB  - We report the development of a novel fluorescent drug sensor from the bacterial
      drug target TEM-1 beta-lactamase through the combined strategy of Val216->Cys216
      mutation and fluorophore labelling for in vitro drug screening. The Val216
      residue in TEM-1 is replaced with a cysteine residue, and the environment
      sensitive fluorophore fluorescein-5-maleimide is specifically attached to the
      Cys216 residue in the V216C mutant for sensing drug binding at the active site.
      The labelled V216C mutant has wild-type catalytic activity and gives stronger
      fluorescence when beta-lactam antibiotics bind to the active site. The labelled
      V216C mutant can differentiate between potent and impotent beta-lactam
      antibiotics and can distinguish active-site binders from non-binders (including
      aggregates formed by small molecules in aqueous solution) by giving
      characteristic time-course fluorescence profiles. Mass spectrometric, molecular
      modelling and trypsin digestion results indicate that drug binding at the active
      site is likely to cause the fluorescein label to stay away from the active site
      and experience weaker fluorescence quenching by the residues around the active
      site, thus making the labelled V216C mutant to give stronger fluorescence in the
      drug-bound state. Given the ancestor's role of TEM-1 in the TEM family, the
      fluorescent TEM-1 drug sensor represents a good model to demonstrate the general
      combined strategy of Val216->Cys216 mutation and fluorophore labelling for
      fabricating tailor-made fluorescent drug sensors from other clinically
      significant TEM-type beta-lactamase variants for in vitro drug screening.

PMID- 25074399
TI  - Editorial Comment to External validation of European Organization for Research
      and Treatment of Cancer and Spanish Urological Club for Oncological Treatment
      scoring models to predict recurrence and progression in Japanese patients with
      non-muscle invasive bladder cancer treated with bacillus Calmette-Guerin.

PMID- 25074401
TI  - Isolated hemopericardium associated with rivaroxaban: first case report.
AB  - Rivaroxaban is a novel anticoagulant approved for use in patients with atrial
      fibrillation for stroke prevention. It is a factor Xa inhibitor, and its activity
      cannot be monitored with use of the international normalized ratio. A 5.6% chance
      of major bleeding is associated with rivaroxaban use, including intracranial and
      gastrointestinal bleeds. We report the first case, to our knowledge, of isolated
      hemopericardium related to rivaroxaban use, which could potentially lead to death
      from cardiac tamponade. A 76-year-old man who was receiving rivaroxaban for
      atrial fibrillation presented to the emergency department with pleuritic chest
      pain and was found to have a hemopericardium. No signs of tamponade were evident,
      and his bleed remained stable after discontinuing rivaroxaban. The patient had
      also been taking saw palmetto, which may have contributed to the bleed by
      increasing rivaroxaban activity. A work-up for other causes of hemopericardium,
      including pacemaker lead misplacement and autoimmune disease-related
      pericarditis, was negative. Use of the Naranjo adverse drug reaction probability
      scale indicated a probable relationship (score of 5) between the patient's
      development of hemopericardium and rivaroxaban use. This case highlights the
      potential for bleeding complications associated with novel anticoagulants. Herbal
      products and various drugs may increase rivaroxaban levels by inhibiting P
      glycoprotein and cytochrome P450 3A4 activity. Clinicians should be aware of
      these potential interactions with rivaroxaban and perform a review of not only
      the patient's drug therapy but also any herbal and food products that could alter
      the levels of anticoagulants. The lack of an antidote and the inability to
      dialyze rivaroxaban is a significant concern in situations of life-threatening
      bleeds. A laboratory test for monitoring rivaroxaban levels may be required for
      its safe use. 

PMID- 25074402
TI  - Three-dimensional hydration layer mapping   on the (10.4) surface of calcite
      using   amplitude modulation atomic force   microscopy.
AB  - Calcite, the most stable modification of calcium carbonate, is a major mineral in
      nature. It is, therefore, highly relevant in a broad range of fields such as
      biomineralization, sea water desalination and oil production. Knowledge of the
      surface structure and reactivity of the most stable cleavage plane, calcite
      (10.4), is pivotal for understanding the role of calcite in these diverse areas.
      Given the fact that most biological processes and technical applications take
      place in an aqueous environment, perhaps the most basic - yet decisive - question
      addresses the interaction of water molecules with the calcite (10.4) surface. In
      this work, amplitude modulation atomic force microscopy is used for three
      dimensional (3D) mapping of the surface structure and the hydration layers above
      the surface. An easy-to-use scanning protocol is implemented for collecting
      reliable 3D data. We carefully discuss a comprehensible criterion for identifying
      the solid-liquid interface within our data. In our data three hydration layers
      form a characteristic pattern that is commensurate with the underlying calcite
      surface.

PMID- 25074400
TI  - Optimal cutoff of the waist-to-hip ratio for detecting cardiovascular risk
      factors among Han adults in Xinjiang.
AB  - BACKGROUND: The optimal cutoff of the waist-to-hip ratio (WHR) among Han adults
      in Xinjiang, which is located in the center of Asia, is unknown. We aimed to
      examine the relationship between different WHRs and cardiovascular risk factors
      among Han adults in Xinjiang, and determine the optimal cutoff of the WHR.
      METHODS: The Cardiovascular Risk Survey was conducted from October 2007 to March
      2010. A total of 14618 representative participants were selected using a four
      stage stratified sampling method. A total of 5757 Han participants were included
      in the study. The present statistical analysis was restricted to the 5595 Han
      subjects who had complete anthropometric data. The sensitivity, specificity, and
      distance on the receiver operating characteristic (ROC) curve in each WHR level
      were calculated. The shortest distance in the ROC curves was used to determine
      the optimal cutoff of the WHR for detecting cardiovascular risk factors. RESULTS:
      In women, the WHR was positively associated with systolic blood pressure,
      diastolic blood pressure, and serum concentrations of serum total cholesterol.
      The prevalence of hypertension and hypertriglyceridemia increased as the WHR
      increased. The same results were not observed among men. The optimal WHR cutoffs
      for predicting hypertension, diabetes, dyslipidemia and >= two of these risk
      factors for Han adults in Xinjiang were 0.92, 0.92, 0.91, 0.92 in men and 0.88,
      0.89, 0.88, 0.89 in women, respectively. CONCLUSIONS: Higher cutoffs for the WHR
      are required in the identification of Han adults aged >= 35 years with a high
      risk of cardiovascular diseases in Xinjiang.

PMID- 25074403
TI  - Experimental reconstruction of cervical esophageal defect with artificial
      esophagus made of polyurethane in a dog model.
AB  - The defect of esophagus after surgical excision in patients is usually replaced
      by autologous stomach, jejunum, or colon. The operation brings severe trauma and
      complications. Using artificial esophagus to replace the defect in situ can
      reduce the operative trauma, simplify the operative procedures, and decrease the
      influence to digestive function. A variety of experiments have been designed for
      developing a practical artificial esophagus. Nevertheless, a safe and reliable
      artificial esophagus is not yet available. The objective is to evaluate the
      possibility of the artificial esophagus made of non-degradable polyurethane
      materials being used in reconstruction of the segmental defect of cervical
      esophagus in beagles, observe the regeneration of esophageal tissue, and gather
      experience for future study. The cervical esophageal defects in 13 beagles were
      designed to 2-cm long and were constructed by the artificial esophagus made of
      non-degradable polyurethane materials. Nutrition supports were given after the
      operation. The operative mortality, anastomotic leakage, migration of artificial
      esophagus, and dysphagia were followed up. The regeneration of the esophageal
      tissues was evaluated by histopathology and immunohistochemical labeled
      streptavidin-biotin method. The surgical procedures were successfully completed
      in all beagles, and 12-month follow-ups were done. Only one beagle died of severe
      infection, and all others survived until being killed. The anastomotic leakage
      occurred in nine beagles, most of them (8/9) were cured after supportive therapy.
      The migration of artificial esophagus occurred in all 12 surviving beagles, and
      one artificial esophagus stayed in situ after migration. All 12 surviving beagles
      showed dysphagia with taking only fluid or soft food. No beagle died of
      malnutrition. The neo-esophagus was composed of granulation tissue, and the inner
      surface was covered by epithelium in 2-3 months completely. But the inner surface
      of neo-esophagus with artificial esophagus staying in situ after migration was
      not covered by epithelium, and the granulation tissue was infiltrated by a great
      deal of inflammatory cells. Antibodies against cytokeratin were positively
      expressed in epithelium of neo-esophagus. Up to 12 months after operation,
      antibodies against smooth muscle actin and desmin were both negatively expressed
      in neo-esophagus. The artificial esophagus made of non-degradable polyurethane
      reconstructing cervical esophageal defect is practicable. Although there are some
      problems, including anastomotic leakage, migration, and dysphagia, they are not
      lethal following good supportive therapy. The esophageal epithelium can
      regenerate with the supporting role of artificial esophagus. In the future,
      deformable artificial esophagus should be improved, and a much longer follow-up
      will be performed to evaluate whether the esophageal gland and skeletal muscle
      can regenerate. 

PMID- 25074404
TI  - HPV vaccination in women aged 27 to 45 years: what do general practitioners
      think?
AB  - BACKGROUND: Although the Human Papillomavirus (HPV) vaccine is registered in
      Australia for females aged 9 to 45 years, females aged 27 to 45 years have shown
      limited vaccine uptake. Our study explored general practitioners' (GPs) views
      concerning HPV vaccination of females in this age group, with particular focus on
      the barriers and the facilitators to the delivery of the HPV vaccine. METHODS:
      Semi-structured telephone interviews were conducted with 24 randomly selected
      general practitioners from metropolitan Melbourne. Questions were based on a
      theoretical framework that explained the barriers and facilitators to
      professional behaviour change. RESULTS: According to the GPs, the major barriers
      to the uptake of the HPV vaccine included the cost of the vaccine, time
      constraints, and the three-dose schedule. Other barriers that were identified
      included GPs' and patients' beliefs that females in this age group were at low
      risk of contracting HPV, lack of awareness about the vaccine, and uncertainty
      about the benefits of this vaccine for females in this age group. In contrast,
      the facilitators that were identified included the availability of the vaccine on
      site, the availability of vaccine clinics or nurses for administering the
      vaccine, the availability of information related to the vaccine either on site or
      online, and positive opinions from experts in the field. CONCLUSIONS: Our study
      has identified some of the barriers and facilitators to the delivery and uptake
      of the HPV vaccine in females aged 27 to 45 years, as perceived by GPs. Further
      studies should be conducted to determine which of these should be targeted or
      prioritised for intervention. The views of women in this age group should also be
      considered as these would also be influential in designing effective intervention
      strategies for improving the delivery and uptake of the HPV vaccine.

PMID- 25074405
TI  - Data sharing: a decade since the publication of the first cohort profile.

PMID- 25074406
TI  - Cohort profile update: the Danish HIV Cohort Study (DHCS).
AB  - The DHCS is a cohort of all HIV-infected individuals seen in one of the eight
      Danish HIV centres after 31 December 1994. Here we update the 2009 cohort profile
      emphasizing the development of the cohort. Every 12-24 months, DHCS is linked
      with the Danish Civil Registration System (CRS) in order to extract an age- and
      sex-matched comparison cohort from the general population, as well as cohorts of
      family members of the HIV-infected patients and of the comparison cohort. The
      combined cohort is linked with CRS, the Danish Cancer Registry, the Danish
      National Hospital Registry, the Danish Registry of Causes of Death, the Danish
      National Prescription Registry, the Attainment Register and the Integrated
      Database for Labour Market Research to get information on vital status,
      migration, cancer, hospital contacts, causes of death, dispensed prescriptions,
      education and employment. Using this design, rates of a range of outcomes have
      been compared between HIV-infected patients and the comparison cohort, as well as
      between families of these two cohorts in order to disaggregate the effects of HIV
      infection and familial/environmental factors. Data can be shared with foreign
      institutions following approval from the Danish Data Protection Agency. Potential
      collaborators can contact the study director, Niels Obel (e-mail:
      niels.obel@regionh.dk). 

PMID- 25074407
TI  - Acinetobacter bohemicus sp. nov. widespread in natural soil and water ecosystems
      in the Czech Republic.
AB  - We investigated the taxonomic status of a phenetically unique group of 25
      Acinetobacter strains which were isolated from multiple soil and water samples
      collected in natural ecosystems in the Czech Republic. Based on the comparative
      sequence analyses of the rpoB, gyrB, and 16S rRNA genes, the strains formed a
      coherent and well separated branch within the genus Acinetobacter. The genomic
      uniqueness of the group at the species level was supported by the low average
      nucleotide identity values (<=77.37%) between the whole genome sequences of
      strain ANC 3994(T) (NCBI accession no. APOH00000000) and the representatives of
      the known Acinetobacter species. Moreover, all 25 strains created a tight cluster
      clearly separated from all hitherto described species based on whole-cell protein
      profiling by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) and shared a unique combination of metabolic and
      physiological properties. The capacity to assimilate l-histidine and the
      inability to grow at 35 degrees C differentiated them from their phenotypically
      closest neighbor, Acinetobacter johnsonii. We conclude that the 25 strains
      represent a novel Acinetobacter species, for which the name Acinetobacter
      bohemicus sp. nov. is proposed. The type strain of A. bohemicus is ANC 3994(T)
      (=CIP 110496(T)=CCUG 63842(T)=CCM 8462(T)). 

PMID- 25074408
TI  - Deletion of membrane-associated Asp23 leads to upregulation of cell wall stress
      genes in Staphylococcus aureus.
AB  - With about 25 000 molecules per cell, Asp23 is one of the most abundant proteins
      in Staphylococcus aureus. Asp23 has been characterized as a protein that,
      following an alkaline shock, accumulates in the soluble protein fraction.
      Transcription of the asp23 gene is exclusively regulated by the alternative sigma
      factor sigma(B) , which controls the response of the bacterium to environmental
      stress. Sequence analysis identified Asp23 as a member of the widely distributed
      Pfam DUF322 family, precluding functional predictions based on its sequence.
      Using fluorescence microscopy we found that Asp23 colocalized with the cell
      membrane of Staphylococcus aureus. Since Asp23 has no recognizable transmembrane
      spanning domains, we initiated a search for proteins that link Asp23 to the cell
      membrane. We identified SAOUHSC_02443 as the Asp23 membrane anchor and have
      renamed it AmaP (Asp23 membrane anchoring protein). Deletion of the asp23 gene
      led to an upregulation of the cell wall stress response. In summary, we have
      identified Asp23 as a membrane-associated protein and we suggest a function for
      Asp23 in cell envelope homoeostasis. 

PMID- 25074409
TI  - Hybrid laparoscopic versus open pylorus-preserving pancreatoduodenectomy:
      retrospective matched case comparison in 80 patients.
AB  - PURPOSE: We compared the outcome of hybrid laparoscopic pylorus-preserving
      pancreatoduodenectomy (lapPPPD) and open PPPD (oPPPD) in a retrospective case
      matched study. METHODS: Patients operated from 2010 to 2013 by lapPPPD were
      matched 1:1 for age, sex, histopathology, American Society of Anesthesiologists
      category and body mass index to oPPPD patients operated from 1996 to 2013.
      RESULTS: Patients eligible for lapPPPD are a risk group due to a high rate of
      soft pancreata. Complication rate and mortality were comparable to oPPPD. There
      was a significantly reduced transfusion requirement and a trend towards shorter
      operation time, less delayed gastric emptying, and reduced hospital stay. The
      main reason for conversion was portal venous tumor adhesion. Patient selection
      changed and operation time and hospital stay decreased with the surgeons'
      experience. CONCLUSION: In selected patients, a hybrid laparoscopic technique of
      pancreatoduodenectomy is feasible with complication rates comparable to the open
      procedure. There seem to be advantages in terms of transfusion requirement,
      operation time, and hospital stay.

PMID- 25074410
TI  - Changes in DNA methylation levels and nuclear distribution patterns after
      microspore reprogramming to embryogenesis in barley.
AB  - Under specific stress treatments, the microspore can be induced in vitro to
      deviate from its gametophytic development and to reprogram towards embryogenesis,
      becoming a totipotent cell and forming haploid embryos. These can further
      regenerate homozygous plants for production of new isogenic lines, an important
      biotechnological tool for crop breeding. DNA methylation constitutes a prominent
      epigenetic modification of the chromatin fiber which regulates gene expression.
      Changes in DNA methylation accompany the reorganization of the nuclear
      architecture during plant cell differentiation and proliferation; however, the
      relationship between global DNA methylation and genome-wide expression patterns
      is still poorly understood. In this work, the dynamics of global DNA methylation
      levels and distribution patterns were analyzed during microspore reprogramming to
      embryogenesis and during pollen development in Hordeum vulgare. Quantification of
      global DNA methylation levels and 5-methyl-deoxycytidine (5mdC)
      immunofluorescence were conducted at specific stages of pollen development and
      after reprogramming to embryogenesis to analyze the epigenetic changes that
      accompany the change of developmental program and cell fate. The results showed
      low DNA methylation levels in microspores and a high increase along pollen
      development and maturation; an intense 5mdC signal was concentrated in the
      generative and sperm nuclei whereas the vegetative nucleus exhibited a weaker DNA
      methylation signal. After inductive stress treatment, low methylation levels and
      faint 5mdC signals were observed in nuclei of reprogrammed microspores and 2-4
      cell proembryos. This data revealed a global DNA hypomethylation during the
      change of the developmental program and first embryogenic divisions. This is in
      contrast with the hypermethylation of generative and sperm cells of the male
      germline during pollen maturation, suggesting an epigenetic regulation after
      induction of microspore embryogenesis. At later embryogenesis stages, global DNA
      methylation progressively increased, accompanying embryo development and
      differentiation events like in zygotic embryos, corroborating that DNA
      methylation is critical for the regulation of gene expression in microspore
      embryogenesis.

PMID- 25074412
TI  - Parents' information and support needs when their child is diagnosed with type 1
      diabetes: a qualitative study.
AB  - AIM AND OBJECTIVE: The aim of this study was to describe and explore parents'
      information and support needs when their child is diagnosed with type 1 diabetes,
      including their views about the timing and chronology of current support
      provision. Our objective was to identify ways in which parents could be better
      supported in the future. DESIGN AND PARTICIPANTS: Semi-structured interviews were
      conducted with 54 parents of children with type 1 diabetes in four paediatric
      diabetes clinics in Scotland. Data were analysed using an inductive, thematic
      approach. FINDINGS: Parents described needing more reassurance after their child
      was diagnosed before being given complex information about diabetes management,
      so they would be better placed psychologically and emotionally to absorb this
      information. Parents also highlighted a need for more emotional and practical
      support from health professionals when they first began to implement diabetes
      regimens at home, tailored to their personal and domestic circumstances. However,
      some felt unable to ask for help or believed that health professionals were
      unable to offer empathetic support. Whilst some parents highlighted a need for
      support delivered by peer parents, others who had received peer support conveyed
      ambivalent views about the input and advice they had received. CONCLUSIONS: Our
      findings suggest that professionals should consider the timing and chronology of
      support provision to ensure that parents' emotional and informational needs are
      addressed when their child is diagnosed and that practical advice and further
      emotional support are provided thereafter, which takes account of their day-to
      day experiences of caring for their child.

PMID- 25074414
TI  - An active supercomplex of NADPH dehydrogenase mediated cyclic electron flow
      around Photosystem I from the panicle chloroplast of Oryza sativa.
AB  - Chloroplast NAD(P)H dehydrogenase-like complex (NDH) plays a crucial role in the
      protection of plants against oxidative stress. In higher plants, NDH interacts
      with Photosystem I (PSI) to form an NDH-PSI supercomplex. However, the
      chloroplast supercomplex with NADPH oxidation activity remains to be identified.
      Here, we reported the identification of a supercomplex of NDH with NADPH
      nitroblue tetrazolium oxidoreductase activity in the chloroplast of rice panicle.
      The active supercomplex from the panicle chloroplast contained higher amounts of
      the NDH subunits (NdhH, NdhK, and NdhA) than that from the flag leaf chloroplast.
      The highly active supercomplex might underlie the high activity of the NADPH
      dependent NDH pathway and the larger proton gradient across thylakoid membranes
      via cyclic electron flow around PSI, as well as the higher maximal photochemical
      efficiency of Photosystem II at the flowering to grain-filling stage. The
      supercomplex is suggested to be essential for the high efficiency of
      photosynthesis and play a protective role in the grain formation in rice plant. 

PMID- 25074413
TI  - PAK1 mediates pancreatic cancer cell migration and resistance to MET inhibition.
AB  - Pancreatic adenocarcinoma (PDAC) is a major unmet medical need and a deeper
      understanding of molecular drivers is needed to advance therapeutic options for
      patients. We report here that p21-activated kinase 1 (PAK1) is a central node in
      PDAC cells downstream of multiple growth factor signalling pathways, including
      hepatocyte growth factor (HGF) and MET receptor tyrosine kinase. PAK1 inhibition
      blocks signalling to cytoskeletal effectors and tumour cell motility driven by
      HGF/MET. MET antagonists, such as onartuzumab and crizotinib, are currently in
      clinical development. Given that even highly effective therapies have resistance
      mechanisms, we show that combination with PAK1 inhibition overcomes potential
      resistance mechanisms mediated either by activation of parallel growth factor
      pathways or by direct amplification of PAK1. Inhibition of PAK1 attenuated in
      vivo tumour growth and metastasis in a model of pancreatic adenocarcinoma. In
      human tissues, PAK1 is highly expressed in a proportion of PDACs (33% IHC score 2
      or 3; n = 304) and its expression is significantly associated with MET positivity
      (p < 0.0001) and linked to a widespread metastatic pattern in patients (p =
      0.067). Taken together, our results provide evidence for a functional role of
      MET/PAK1 signalling in pancreatic adenocarcinoma and support further
      characterization of therapeutic inhibitors in this indication.

PMID- 25074415
TI  - Pharmacological management of narcolepsy and cataplexy in pediatric patients.
AB  - Narcolepsy is a neurological disorder frequently occurring from childhood and
      persisting through adolescence and adulthood. Individuals suffering from
      narcolepsy exhibit excessive daytime somnolence, sleep attacks, cataplexy,
      dysomnia, metabolic perturbations including weight gain, and problems in social
      interaction and academic performance. The prevalence of narcolepsy in childhood
      is not known but can be estimated from adult studies to be greater than 20-60 per
      100,000 in Western countries. The 2009 (A) H1N1 vaccination campaign led to an
      increase of narcoleptic cases both in children and in adults, supporting the
      autoimmune hypothesis of the disease. This article focuses on the epidemiology,
      etiology, and particularities of treatment in pediatric narcolepsy and details
      the effects of the drugs used to treat this condition, including recent trends in
      the field. Future therapeutic directions are also discussed. At present,
      medications used to treat children or adolescents have shown efficacy mostly
      based on clinical experience, given the lack of level 1 evidence-based studies in
      the pediatric population. Therefore, most compounds used in adult narcolepsy to
      target clinical symptoms such as wake-promoting or anticataplectic agents are
      prescribed off-label in pediatric patients. Published research shows the benefit
      of drug therapy for narcoleptic children, but these must be dispensed with
      caution in the absence of well conducted clinical trials. 

PMID- 25074416
TI  - No association between wolframin gene H611R polymorphism and mood disorders:
      evidence from 2,570 subjects.
AB  - BACKGROUND: In the past few decades, a number of studies have investigated the
      association of the wolframin (WFS1) gene H611R polymorphism with mood disorders,
      but the findings are not always consistent. AIMS: The objective of the present
      study is to assess the association between WFS1 gene H611R polymorphism and mood
      disorders by using a meta-analysis. METHODS: A comprehensive literature search of
      PubMed, Excerpta Medica Database, Elsevier Science Direct and China National
      Knowledge Infrastructure databases was conducted to identify relevant articles,
      with the last report up to April 15, 2014. Pooled odds ratio (OR) with 95%
      confidence interval (CI) was estimated. RESULTS: Seven studies including 1318
      cases and 1252 controls were selected from potentially relevant articles. This
      meta-analysis showed that there was no significant association between WFS1 gene
      H611R polymorphism and mood disorders (R vs. H: OR = 0.93, 95% CI = 0.82-1.05, P
      = 0.22; HR+ RR vs. HH: OR = 0.98, 95% CI = 0.82-1.17, P = 0.80; RR vs. HH+ HR: OR
      = 0.84, 95% CI = 0.67-1.04, P = 0.11; RR vs. HH: OR = 0.86, 95% CI = 0.67-1.10, P
      = 0.24; HR vs. HH: OR = 1.03, 95% CI = 0.78-1.36, P = 0.83). In subgroup analyses
      by ethnicity, we did not detect any significant association of this polymorphism
      with mood disorders in Caucasian and Asian populations (P > 0.05). In subgroup
      analyses by types of mood disorders, we also did not detect any significant
      association of this polymorphism with bipolar disorder or major depressive
      disorder (P > 0.05). CONCLUSIONS: The results of this meta-analysis suggest that
      there is no association between WFS1 gene H611R polymorphism and mood disorders.

PMID- 25074417
TI  - Phase II study of accelerated hypofractionated three-dimensional conformal
      radiotherapy for stage T1-3 N0 M0 non-small cell lung cancer: NCIC CTG BR.25.
AB  - BACKGROUND: A multi-institutional phase II trial was performed to assess a
      hypofractionated accelerated radiotherapy regimen for early stage non-small cell
      lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely
      available. METHODS: Eighty patients with biopsy-proven, peripherally located, T1
      3 N0 M0 NSCLC were enrolled. Eligible patients received 60 Gy in 15 fractions
      using a three-dimensional conformal technique without inhomogeneity correction.
      The gross tumour volume (GTV) was the primary tumor only, and the planning target
      volume (PTV) margin was 1.0 to 1.5cm. The primary endpoint was the 2-year primary
      tumor control rate. Toxicities were measured using the Common Terminology
      Criteria for Adverse Events version 3.0. RESULTS: The median follow-up of
      patients was 49 months (range = 21-63 months). The median age of patients was
      75.9 years. The actuarial rate of primary tumor control was 87.4% (95% confidence
      interval [CI] = 76.2% to 93.5%) at 2 years. Overall survival was 68.7% (95% CI =
      57.2% to 77.6%) at 2 years. The actuarial rates of developing regional and
      distant relapse at 2 years were 8.8% (95% CI = 4.1% to 18.7%) and 21.6% (95% CI =
      13.5% to 33.5%), respectively. Tumor size greater than 3cm was associated with an
      increased risk of developing distant relapse (hazard ratio = 3.11; 95% CI = 1.30
      to 7.42; two-sided log-rank test P = .007). The most common grade 3+ toxicities
      were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10.0%)
      CONCLUSIONS: Conformal radiotherapy to a dose of 60 Gy in 15 fractions resulted
      in favorable primary tumor control and overall survival rates in patients with T1
      3 N0 M0 NSCLC. Severe toxicities were uncommon with this relatively simple
      treatment technique.

PMID- 25074418
TI  - Extended length of stay after surgery: complications, inefficient practice, or
      sick patients?
AB  - IMPORTANCE: With the health policy focus on shifting risk to hospitals and
      physicians, hospital leaders are increasing efforts to reduce excessive resource
      use, such as patients with extended length of stay (LOS) after surgery. However,
      the degree to which extended LOS represents complications, patient illness, or
      inefficient practice style is unclear. OBJECTIVE: To examine the influence of
      complications on the variance in hospitals' extended LOS rates after colorectal
      resections. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study
      performed from January 1 through December 31, 2009, we analyzed data from the
      2009 American College of Surgeons National Surgical Quality Improvement Program.
      Study participants were 22 664 adults undergoing colorectal resections in 199
      hospitals. EXPOSURES: Inpatient complications recorded in the American College of
      Surgeons National Surgical Quality Improvement Program registry. Inpatient
      complications were identified by the association of the complication's
      postoperative date with the patient's surgical discharge date. MAIN OUTCOME AND
      MEASURE: Hospitals' risk-adjusted extended LOS rates, defined as the proportion
      of patients with a hospital stay greater than the 75th percentile for the entire
      cohort. RESULTS: A total of 2177 patients (42.8%) with extended LOSs did not have
      a documented inpatient complication. Although there was wide variation in risk
      adjusted extended LOS (14.5%-35.3%) and risk-adjusted inpatient complication
      (12.1%-28.5%) rates, there was only a weak correlation (Spearman rho = 0.56, P <
      .001) between the two. Only 52.0% of the variation in hospitals' extended LOS
      rates was attributable to hospitals' inpatient complication rates. CONCLUSIONS
      AND RELEVANCE: Much of the variation in hospitals' risk-adjusted extended LOS
      rates is not attributable to patient illness or complications and therefore most
      likely represents differences in practice style. Efforts to reduce excess
      resource use should focus on efficiency of care, such as increased adoption of
      enhanced recovery pathways.

PMID- 25074419
TI  - Enhancement of non-heme iron absorption by anchovy (Engraulis japonicus) muscle
      protein hydrolysate involves a nanoparticle-mediated mechanism.
AB  - The mechanisms by which meat enhances human absorption of non-heme iron remain
      unknown. Recently, anchovy (Engraulis japonicus) muscle protein hydrolysate
      (AMPH) was found to mediate the formation of nanosized ferric hydrolysis products
      in vitro. The current paper evaluates the effects of AMPH on the bioavailability
      and the intestinal speciation of non-heme iron in rats, followed by an
      investigation of cellular uptake pathways of in vitro-formed AMPH-stabilized
      nanosized ferric hydrolysis products (ANPs) by polarized human intestinal
      epithelial (Caco-2) cells. The hemoglobin regeneration efficiencies in anemic
      rats followed the order ferric citrate (9.79 +/- 2.02%) < commercial bare alpha
      Fe2O3 nanoparticles (16.37 +/- 6.65%) < mixture of ferric citrate and AMPH (40.33
      +/- 6.36%) ~ ferrous sulfate (40.88 +/- 7.67%) < ANPs (56.25 +/- 11.35%).
      Percentage contents of intestinal low-molecular-weight iron in the groups of
      FC+AMPH, FeSO4, and ANPs were significantly lower than the corresponding
      hemoglobin regeneration efficiencies (P < 0.05), providing strong evidence for
      the involvement of nanosized iron in intestinal iron absorption from FC+AMPH,
      FeSO4, and ANPs. Calcein-fluorescence measurements of the labile iron pool of
      polarized Caco-2 cells revealed the involvement of both divalent transporter 1
      and endocytosis in apical uptake of ANPs, with endocytosis dominating at acidic
      extracellular pH. Overall, AMPH enhancement of non-heme iron absorption involves
      a nanoparticle-mediated mechanism. 

PMID- 25074420
TI  - Optimizing a ultrahigh pressure liquid chromatography-time of flight-mass
      spectrometry approach using a novel sub-2MUm core-shell particle for in depth
      lipidomic profiling of Caenorhabditis elegans.
AB  - Lipid profiling or lipidomics is currently applied in many different research
      fields. It refers to the global analysis of a samples lipid content using
      different analytical chemistry methods, with mass spectrometry as the mostly
      employed technology. We developed a comprehensive in-depth analysis method for
      the lipidome of the soil-dwelling nematode Caenorhabitis elegans, a widely used
      model organism. Four different columns were compared with a generic gradient and
      a novel sub-2-MUm core-shell column, Waters Cortecs C18, showed superior
      performance in case of chromatographic peak characteristics, e.g. plate numbers
      and number of detected lipid features. Retention time deviation was generally
      less than 1% within one column and below 5% for columns from different batches.
      Intensity variation was lower than 30% for most detected features. Improved
      chromatographic separation showed enhanced resolution for isomeric lipids and
      allowed collection of highly detailed MS/MS spectra for lipid identification. In
      total 1304 lipid features were detected in positive ionization mode and 265 in
      negative mode. Lipids from different classes were annotated and MS/MS spectra
      obtained by data dependent fragmentation were used for identification purposes. 

PMID- 25074421
TI  - Coating of nanoparticles on cryogel surface and subsequent double-modification
      for enhanced ion-exchange capacity of protein.
AB  - A novel composite cryogel monolith was developed by coating poly(glycidyl
      methacrylate) nanoparticles (NPs) onto the pore wall surface of poly(acrylamide)
      cryogel. The NPs-coated column was double-modified with poly(ethylenimine) (PEI)
      and diethylaminoethyl in sequence. Scanning electron microscopy revealed the
      dense coating of the NPs on the cryogel surface, but the NPs-coating did not
      result in distinct changes of the column porosity and permeability. The rough
      pore wall surface and extended polymer chains offered more binding sites, so the
      dynamic binding capacity of the composite cryogel bed for bovine serum albumin
      reached 11.7mg/mL bed volume at a flow rate of 6cm/min, which was 4.2 times
      higher than that of the cryogel bed modified with PEI without coating NPs
      (2.8mg/mL). The binding capacity as well as column efficiency decreased only
      slightly with increasing flow rate from 0.6 to 12cm/min. The results indicated
      that the strategy of NPs-coating incorporating with double ion-exchanger
      modifications is promising for enhancing cryogel capacities, and the novel
      material would be useful for high-speed protein chromatography. 

PMID- 25074423
TI  - Critical differences in chromatographic properties of silica- and polymer-based
      monoliths.
AB  - Chromatographic analytical columns containing porous monolithic beds based on
      cross-linked polymers and derivatized silica have now been commercially available
      for several years and, despite some apparent conceptual similarities, are
      marketed and utilized for quite different chromatographic applications. While
      this distinction is well-accepted by users, the fundamental differences in
      chromatographic behavior of these materials that lead to this clear distinction
      in their primary application areas have not yet been systematically studied. To
      this end, the present experimental study investigates differences in the apparent
      chromatographic characteristics when using small molecules with commercially
      available monolithic reversed-phase analytical columns based on poly(styrene-co
      divinyl benzene) and C18-derivatized silica. Relevant practical information is
      obtained from measurements made by "arrested elution" of non-retained and
      retained solutes and chromatographic elution performance across a wide range of
      retention factors with a set of structurally similar small molecules.
      Observations of apparent diffusion probed with "arrested elution" experiments and
      mass transport inferred from the observed efficiency at increased flow velocity
      in the monolithic structures (both under retained and non-retained conditions)
      lead to the conclusion that fundamentally different solute transport behavior is
      operative. The silica-based monolithic materials are used to establish a
      "reference" for comparison to observations with cross-linked porous polymeric
      monolithic materials. Despite the differences in morphology, chromatographic
      properties have their origin in the underlying physical structure of pore space.
      The derivatized surfaces in silica-based materials have their counterpart in pore
      fluid gel interfaces in polymeric monoliths. The pore-fluid gel interfaces have
      their origin in varying solvation of polymer by eluent components. Consequently,
      they allow varying permeation of small molecules into the solvated polymer via
      partition. The traversing of small molecules through the polymer monolith's
      complex nanoscale physical structure plays a key factor when rationalizing any
      chromatographic performance as seen in the slopes of plate height curves which
      vary dramatically with mobile phase composition and solute identity. 

PMID- 25074422
TI  - Comprehensive ultra-performance liquid chromatographic separation and mass
      spectrometric analysis of eicosanoid metabolites in human samples.
AB  - Over the past decade, the number of known eicosanoids has expanded immensely and
      we have now developed an ultra-performance liquid chromatography-electrospray
      ionization triple quadrupole mass spectrometric (UPLC-QTRAP/MS/MS) method to
      monitor and quantify numerous eicosanoids. The UPLC-QTRAP/MS/MS approach utilizes
      scheduled multiple reaction monitoring (MRM) to optimize sensitivity, number of
      metabolites that can be analyzed and the time requirement of the analysis. A
      total of 184 eicosanoids including 26 deuterated internal standards can be
      separated and monitored in a single 5min UPLC run. To demonstrate a practical
      application, human plasma samples were analyzed following solid-phase extraction
      (SPE) and the recovery rate and matrix effects were determined for the 26
      deuterated internal standards added to the plasma. The method was validated and
      shown to be sensitive with the limit of quantitation at pg levels for most
      compounds, accurate with recovery rates of 70-120%, and precise with a CV<30 for
      all compounds. Also, the method showed a linear response over a range spanning
      several orders of magnitude. In a QC human plasma sample, we identified and
      rigorously quantified over 120 eicosanoids. 

PMID- 25074424
TI  - Novel cell lines isolated from mouse embryonic stem cells exhibiting de novo
      methylation of the E-cadherin promoter.
AB  - Mouse embryonic stem cells (mESCs) and epiblast stem cells represent the naive
      and primed pluripotent states, respectively. These cells self-renew via distinct
      signaling pathways and can transition between the two states in the presence of
      appropriate growth factors. Manipulation of signaling pathways has therefore
      allowed the isolation of novel pluripotent cell types such as Fibroblast growth
      factor, Activin and BIO-derived stem cells and IESCs. However, the effect of cell
      seeding density on pluripotency remains unexplored. In this study, we have
      examined whether mESCs can epigenetically regulate E-cadherin to enter a primed
      like state in response to low cell seeding density. We show that low density
      seeding in the absence of leukaemia inhibitory factor (LIF) induces decreased
      apoptosis and maintenance of pluripotency via Activin/Nodal, concomitant with
      loss of E-cadherin, Signal transducer and activator of transcription
      phosphorylation, and chimera-forming ability. These cells, E-cadherin negative
      proliferating stem cells (ENPSCs) can be reverted to a naive phenotype by
      addition of LIF or forced E-cadherin expression. However, prolonged culture of
      ENPSCs without LIF leads to methylation of the E-cadherin promoter (ENPSC(M)),
      which cannot be reversed by LIF supplementation, and increased histone H3K27 and
      decreased H3K4 trimethylation. Transcript analysis of ENPSC(M) revealed a primed
      like phenotype and their differentiation leads to enrichment of neuroectoderm
      cells. The generation of ENPSCs is similar to tumorigenesis as ENPSCs exhibit
      transcript alterations associated with neoplasia, hyperplasia, carcinoma, and
      metastasis. We therefore describe a novel cell model to elucidate the role of E
      cadherin in pluripotency and to investigate epigenetic regulation of this gene
      during mESC differentiation and tumor metastasis.

PMID- 25074425
TI  - Verification of NOx emission inventories over North Korea.
AB  - In this study, the top-down NOx emissions estimated from satellite observations
      of NO2 vertical column densities over North Korea from 1996 to 2009 were
      analyzed. Also, a bottom-up NOx emission inventory from REAS 1.1 from 1980 to
      2005 was analyzed with several statistics. REAS 1.1 was in good agreement with
      the top-down approach for both trend and amount. The characteristics of NOx
      emissions in North Korea were quite different from other developed countries
      including South Korea. In North Korea, emissions from industry sector was the
      highest followed by transportation sector in the 1980s. However, after 1990, the
      NOx emissions from other sector, mainly agriculture, became the 2nd highest.
      Also, no emission centers such as urban areas or industrial areas were
      distinctively observed. Finally, the monthly NOx emissions were high during the
      warm season. 

PMID- 25074426
TI  - Quality of life in a large cohort of adult Brazilian patients with 46,XX and
      46,XY disorders of sex development from a single tertiary centre.
AB  - OBJECTIVE: Few studies have focused on the quality of life (QoL) of patients with
      disorders of sex development (DSD). Our aim was to evaluate QoL in DSD patients
      with defined diagnoses followed until adulthood in a single tertiary centre.
      PATIENTS AND METHODS: Adult patients with DSD (56 patients with 46,XX DSD - 49
      with female social sex and 7 with male social sex as well as 88 patients with
      46,XY DSD - 54 with female social sex and 34 with male social sex). MEASUREMENTS:
      QoL using WHOQOL-Bref questionnaire. RESULTS: Both patients with 46,XX DSD and
      patients with 46,XY DSD had similar QoL scores on the WHOQOL-Bref, comparable to
      the scores of the Brazilian general population. The chronological age at the
      start of treatment was negatively and significantly associated with general QoL
      score. Patients with male social sex DSD had better scores on the psychological
      domain than patients with female social sex DSD, as found in the Brazilian
      general population. In addition, among the 46,XY DSD group, the male social sex
      patients had better QoL compared with the female social sex patients. There was a
      positive and significant correlation between sexual performance and general QoL,
      although it explained only 4% of the variability of the general QoL score. The
      most influencing variables were general health, positive feelings and
      spirituality, religion and personal beliefs, each of them contributing with 18%
      of the variability of the general QoL score. CONCLUSION: Our large cohort of
      adult patients with DSD, which was followed by a multidisciplinary team in a
      single tertiary centre, had good QoL in adulthood; in addition, late treatment
      compromised the QoL of patients with DSD, whereas sexual performance has little
      influence on QoL.

PMID- 25074427
TI  - Attention Problems and Stability of WISC-IV Scores Among Clinically Referred
      Children.
AB  - We examined the stability of Wechsler Intelligence Scale for Children-Fourth
      Edition (WISC-IV) scores among 51 diverse, clinically referred 8- to 16-year-olds
      (M(age) = 11.24 years, SD = 2.36). Children were referred to and tested at an
      urban, university-based training clinic; 70% of eligible children completed
      follow-up testing 12 months to 40 months later (M = 22.05, SD = 5.94). Stability
      for index scores ranged from .58 (Processing Speed) to .81 (Verbal
      Comprehension), with a stability of .86 for Full-Scale IQ. Subtest score
      stability ranged from .35 (Letter-Number Sequencing) to .81 (Vocabulary). Indexes
      believed to be more susceptible to concentration (Processing Speed and Working
      Memory) had lower stability. We also examined attention problems as a potential
      moderating factor of WISC-IV index and subtest score stability. Children with
      attention problems had significantly lower stability for Digit Span and Matrix
      Reasoning subtests compared with children without attention problems. These
      results provide support for the temporal stability of the WISC-IV and also
      provide some support for the idea that attention problems contribute to children
      producing less stable IQ estimates when completing the WISC-IV. We hope our
      report encourages further examination of this hypothesis and its implications.

PMID- 25074428
TI  - Single cytidine units-templated syntheses of multi-colored water-soluble Au
      nanoclusters.
AB  - Ultra-small metallic nanoparticles, or so-called "nanoclusters" (NCs), have
      attracted considerable interest due to their unique optical properties that are
      different from both larger nanoparticles and single atoms. To prepare high
      quality NCs, the stabilizing agent plays an essential role. In this work, we have
      revealed and validated that cytidine and its nucleotides (cytidine 5'
      monophosphate or cytidine 5'-triphosphate) can act as efficient stabilizers for
      syntheses of multicolored Au NCs. Interestingly, Au NCs with blue, green and
      yellow fluorescence emissions are simultaneously obtained using various pH
      environments or reaction times. The transmission electron microscopy verifies
      that the size of Au NCs ranges from 1.5 to 3 nm. The X-ray photoelectron
      spectroscopy confirms that only Au (0) species are present in NCs. Generally, the
      facile preparation of multicolored Au NCs that are stabilized by cytidine units
      provides access to promising candidates for multiple biolabeling applications. 

PMID- 25074429
TI  - Differential effects of fluoride during osteoblasts mineralization in C57BL/6J
      and C3H/HeJ inbred strains of mice.
AB  - The behavior of fluoride ions in biological systems has advantages and problems.
      On one hand, fluoride could be a mitogenic stimulus for osteoblasts. However,
      high concentrations of this element can cause apoptosis in rat and mouse
      osteoblasts. Toward an understanding of this effect, we examined the role of
      sodium fluoride (NaF) in two mouse calvaria osteoblasts during the mineralization
      process. The animals used were C3H/HeJ (C3) and C57BL/6J (B6) mice. The calvaria
      cells were cultured for 28 days in the presence of several doses of NaF (0, 5,
      10, 25, 50, and 75 MUM), and we performed the assays: mineralized nodule
      measurements, alkaline phosphatase (ALP) activity, determination of type I
      collagen, and matrix metalloproteinase-2 (MMP-2) activity. The results showed no
      effects on alkaline phosphatase activity but decreased mineralized nodule
      formation. In B6 cells, the NaF effect was already seen with 10 MUM of NaF and a
      greater increase of cellular type I collagen, and MMP-2 activity was upregulated
      after 7 days of NaF exposure. C3 osteoblasts showed a reduction in the
      mineralization pattern only after 50 MUM of NaF with a slight increase of type I
      collagen and downregulation of MMP-2 activity during the mineralization period.
      In conclusion, fluoride affects the production and degradation of the
      extracellular matrix during early onset and probably during the mineralization
      period. Additionally, the genetic factors may contribute to the variation in cell
      response to fluoride exposure, and the differences observed between the two
      strains could be explained by an alteration of the bone matrix metabolism
      (synthesis and degradation).

PMID- 25074430
TI  - Increased oxidative stress and altered levels of nitric oxide and peroxynitrite
      in Tunisian patients with chronic obstructive pulmonary disease: correlation with
      disease severity and airflow obstruction.
AB  - This study was aimed to evaluate the oxidant-antioxidant imbalance in the
      pathogenesis of chronic obstructive pulmonary disease (COPD) in Tunisians. We
      assessed 16 parameters related to the oxidative status that include
      malondialdehyde (MDA), total protein carbonyls (PCs), and advanced oxidation
      protein products (AOPP). We also examined the activity of glutathione peroxydase
      (GSH-Px), catalase, and superoxide dismutase (SOD) in the plasma and
      erythrocytes. Levels of total thiols, reduced glutathione (GSH), total
      antioxidant status (TAS), hydrogen peroxide, ascorbic acid, iron, and protein
      sulfhydryls were determined using spectrophotometry. We also evaluated the level
      of nitric oxide (NO) and peroxynitrite in plasma from COPD patients and healthy
      controls. Estimation of DNA damage was determined using the comet assay.
      Pulmonary functional tests were performed by body plethysmography. Levels of MDA,
      PC, DNA damage, and AOPP were significantly increased while total thiols, GSH,
      and TAS were decreased in COPD patients. GSH-Px activity was higher in COPD
      patients while no difference was found for catalase and SOD. We also observed a
      lower level of NO and peroxynitrite in COPD patients. Decreased levels of
      peroxynitrite were found to correlate with disease progression, as well as with
      forced expiratory volume in 1 s/forced vital capacity among COPD patients.
      Multivariate analysis revealed that NO is associated with pathological pathways
      that help to predict patient outcome independently of the degree of airflow
      obstruction. These results indicate the presence of a systemic oxidative stress
      and highlight the importance of NO and peroxynitrite as major effectors in COPD
      development and airflow obstruction.

PMID- 25074431
TI  - Coexistence of frontal fibrosing alopecia and discoid lupus erythematosus of the
      scalp in 7 patients: just a coincidence?

PMID- 25074432
TI  - [Nursing: a new phase].

PMID- 25074433
TI  - Prognostic factors affecting disease-free survival in patients at age 35 or
      younger with invasive breast cancer.
AB  - AIM: Our aim is to determine the disease-free survival (DFS) rate, and to
      investigate the prognostic factors among patients with invasive breast cancer at
      age 35 or younger. PATIENTS AND METHOD: The medical records of the 67 patients
      who underwent surgery for invasive breast cancer were retrospectively reviewed.
      Potential prognostic factors that affect the DFS were investigated. DFS curves
      were obtained using the Kaplan-Meier method. The comparisons were made by the
      long-rank test. The prognostic factors affecting the DFS were determined by
      stepwise Cox proportional hazard regression test. The P value < 0.05 was accepted
      as significant. RESULTS: The median age was 32 (range, 23-35). The median follow
      up interval was 55 months (range, 10-108). The 5-year DFS rate was 69.3%. In
      univariate analysis the number of pathologic axillary lymph nodes (p=0.035),
      triplenegative status (p=0.014) and tumor size (p= 0.004) were found to be the
      prognostic factors affecting the DFS. The 5-year DFS rate was 81% in non-triple
      negative patients, whereas this was 35% in triple-negative patients. In the
      multivariate analysis, triple-negative status was the only independent prognostic
      factor which affected the DFS adversely (HR: 1.48, CI: 0.66-082, p=0.027).
      CONCLUSION: Triple-negative status was found to be the only independent and
      adverse prognostic factor which affects the DFS in patients with invasive breast
      cancer at age 35 or younger. KEY WORDS: Breast cancer, Disease-free survival,
      Triple negative breast cancer, Young age.

PMID- 25074434
TI  - BCLC stage B hepatocellular carcinoma and transcatheter arterial
      chemoembolization: a 20-year survey by the Italian Liver Cancer group.
AB  - BACKGROUND & AIMS: Significant proportion of Hepatocellular Carcinoma (HCC) cases
      are diagnosed in stage B of Barcelona Clinic Liver Cancer (BCLC) algorithm, in
      which the standard of care is Transcatheter Arterial ChemoEmbolization (TACE). We
      aimed to ascertain adherence to current guidelines, survival and prognostic
      factors in BCLC stage B patients. METHODS: From 3027 HCC cases recruited from
      1986 to 2008 by the Italian Liver Cancer group (2430 with data allowing a correct
      allocation in the BCLC system), a retrospective analysis was conducted on those
      diagnosed in BCLC stage B (405 patients, 17%). Statistics were performed with
      Kaplan-Meier (log rank) method and Cox multivariate analysis. RESULTS: Median
      overall survival in BCLC stage B patients was 25 months (Confidence Interval -
      C.I. - 22-28 months) with a 5-year survival of 18%. Child-Pugh class, oesophageal
      varices and Alpha-foetoprotein (AFP) were the independent predictors of survival.
      TACE was applied in 40% of cases and did not offer the longest survival in
      comparison with surgical or percutaneous treatments (median 27 months vs. 37 and
      36 months, respectively) (P < 0.001). BCLC stage B patients undergoing radical
      treatments were more frequently in Child-Pugh class A and had a significantly
      lower number of lesions; patients undergoing best supportive care were frequently
      in Child-Pugh class B and had a multifocal disease. Survival after TACE did not
      significantly increase over time. CONCLUSIONS: In clinical practice, TACE cannot
      be considered the best approach for BCLC stage B patients who represent a
      heterogeneous population and are often suitable for more aggressive therapies,
      which lead to a better survival.

PMID- 25074436
TI  - Plasma S100A12 and soluble receptor of advanced glycation end product levels and
      mortality in chronic kidney disease Stage 5 patients.
AB  - BACKGROUND: Alterations in the advanced glycation end-products (AGE)-receptor of
      AGE (RAGE) system are linked to several chronic diseases, which may result from
      vascular damage. A high circulating level of the pro-inflammatory RAGE-ligand
      S100A12, also known as EN-RAGE, is thought to promote while a high level of
      soluble RAGE (sRAGE) is thought to protect against development of atherosclerotic
      cardiovascular disease (CVD). We evaluated circulating S100A12 and sRAGE in
      relation to clinical characteristics, nutritional status, inflammation and
      mortality risk in chronic kidney disease (CKD) Stage 5 patients starting on
      dialysis. METHODS: Plasma S100A12 and sRAGE, biomarkers of inflammation and
      nutritional status, and comorbidities were investigated in 200 CKD Stage 5
      patients [median age of 56 years, 62% men and median glomerular filtration rate
      (GFR) of 6.2 mL/min/1.73 m(2)] in conjunction with initiation of dialysis
      therapy. Associations between mortality risk and S100A12 or sRAGE were assessed
      after a median follow-up period of 23 months. In addition, for comparative
      analyses, S100A12 and sRAGE levels were assessed also in 58 haemodialysis and 78
      peritoneal dialysis patients after 1 year of dialysis, 56 CKD Stages 3-4 patients
      and 50 community-based control subjects. RESULTS: The median level of S100A12 was
      4-fold higher, median sRAGE 2.4 higher and median ratio S100A12/sRAGE 2.27 times
      higher in CKD 5 patients than in controls. Similar alterations were observed in
      CKD 3-4 patients; however, CKD 5 patients had a higher median level of sRAGE than
      the CKD 3-4 patients. In the CKD 5 patients, S100A12 levels were higher in those
      with diabetes or CVD than in those without these comorbidities. Furthermore,
      S100A12 correlated with high-sensitivity C-reactive protein (hsCRP) levels (rho =
      0.53; P < 0.001) and a 1-SD higher level of S100A12 associated with increased all
      cause mortality risk (hazard ratio 1.32, 95% confidence interval 1.01-1.73) after
      adjustment for age, sex, comorbidity, nutritional status and inflammation
      (hsCRP). In the CKD 5 patients, sRAGE correlated negatively with GFR (rho = 
      0.26; P < 0.01) but sRAGE did not associate with hsCRP, comorbidities or
      mortality. CONCLUSIONS: Plasma concentrations of sRAGE, S100A12 and the ratio
      S100A12/sRAGE, are markedly elevated in CKD 5 patients starting on dialysis as
      well as in CKD 3-4 patients and prevalent dialysis patients suggesting that these
      alterations are typical for patients with moderate or severe CKD. In CKD 5
      patients, an increased concentration of S100A12 are associated with inflammation,
      comorbidities and increased mortality risk whereas no such associations were
      observed for sRAGE. These results suggest that while high plasma S100A12 is an
      independent predictor of increased mortality risk, sRAGE does not seem to be a
      valid risk marker in this patient population.

PMID- 25074437
TI  - Goal attainment following upper-limb botulinum toxin-A injections: are we
      facilitating achievement of client-centred goals?
AB  - OBJECTIVES: Evaluate upper-limb goal attainment following botulinum toxin-A, map
      goals to the International Classification of Functioning, Disability and Health
      (ICF) and explore associations between client goals, clinical indicators of
      spasticity and the Botulinum Toxin-A injection strategy adopted by the treating
      physician. DESIGN: Pre-test/post-test. PARTICIPANTS: Twenty-eight community
      dwelling adults with acquired brain injury. METHODS: Goal attainment was measured
      using the Goal Attainment Scale (GAS) 4 weeks post-injection. Goals were linked
      to the ICF. Clinical measures including the Modified Ashworth Scale (MAS),
      Tardieu Spasticity Angle (TSA) and Action Research Arm Test (ARAT) were collected
      pre-injection for determining association with injection strategy. RESULTS: Goals
      represented the ICF domains of Body Structure/Function and
      Activity/Participation. Approximately half the goals were achieved 4 weeks post
      injection and GAS T-scores improved significantly. Activity/Participation goals
      were equally likely to be achieved as Body Structure/Function goals. Pre
      injection ARAT scores were correlated with GAS change, whereas MAS and TSA scores
      were not. TSA was a stronger indicator of muscle selection for botulinum toxin-A
      injections than MAS. Goals were directly associated with botulinum toxin-A
      injections for distal hand function, but not for proximal upper-limb function.
      CONCLUSION: Goal setting and review provides a clinically useful process for
      measuring upper-limb botulinum toxin-A outcomes.

PMID- 25074435
TI  - Personalized medicine approaches for colon cancer driven by genomics and systems
      biology: OncoTrack.
AB  - The post-genomic era promises to pave the way to a personalized understanding of
      disease processes, with technological and analytical advances helping to solve
      some of the world's health challenges. Despite extraordinary progress in our
      understanding of cancer pathogenesis, the disease remains one of the world's
      major medical problems. New therapies and diagnostic procedures to guide their
      clinical application are urgently required. OncoTrack, a consortium between
      industry and academia, supported by the Innovative Medicines Initiative,
      signifies a new era in personalized medicine, which synthesizes current
      technological advances in omics techniques, systems biology approaches, and
      mathematical modeling. A truly personalized molecular imprint of the tumor micro
      environment and subsequent diagnostic and therapeutic insight is gained, with the
      ultimate goal of matching the "right" patient to the "right" drug and identifying
      predictive biomarkers for clinical application. This comprehensive mapping of the
      colon cancer molecular landscape in tandem with crucial, clinical functional
      annotation for systems biology analysis provides unprecedented insight and
      predictive power for colon cancer management. Overall, we show that major
      biotechnological developments in tandem with changes in clinical thinking have
      laid the foundations for the OncoTrack approach and the future clinical
      application of a truly personalized approach to colon cancer theranostics. 

PMID- 25074438
TI  - AurkA inhibitors enhance the effects of B-RAF and MEK inhibitors in melanoma
      treatment.
AB  - BACKGROUND: Aurora kinase A (AurkA) is over-expressed in melanoma and its
      inhibition has been observed to limit tumor growth, suggesting a potential role
      in melanoma treatment. METHODS: A human melanoma cell line with the B-RAF (V600E)
      mutation (A375mel) was exposed to B-RAF inhibitor (GSK2118436), MEK inhibitor
      (GSK1120212) and AurkA inhibitor (MLN8054) as single agents or in various
      combinations (BRAF plus AurkA inhibitor, MEK plus AurkA inhibitor or triple
      combination BRAF plus MEK plus AurkA inhibitor). Cell proliferation was assessed
      using xCELLigence technology. Total protein extracts were examined for p53 and c
      Myc protein expression by Western blot analysis. Drug anti-tumor effects were
      further assessed using a 3D-human melanoma skin reconstruction model, in which
      tissues were incubated with serum-free medium containing control, B-RAF plus MEK
      inhibitor, MEK plus AurkA inhibitor or the triple combination. RESULTS: AurkA
      inhibitor plus B-RAF inhibitor, AurkA inhibitor plus MEK inhibitor or triple
      combination had a markedly greater anti-proliferative effect on A375 (BRAFV600E)
      melanoma cells than single agents. In the 3D human skin model, the triple
      combination had a greater anti-tumor effect at the epidermal/dermal junction than
      control or either double combination. However, S-100 and Ki-67 positively stained
      spindle-shaped cells were detected in the dermal stratum, suggesting the presence
      of alive and proliferating melanoma cells. CONCLUSIONS: These findings provide
      new prospects for melanoma research, including combined B-RAF/AurkA inhibition
      for B-RAF mutated melanomas and MEK/AurkA inhibitor combination for patients
      without B-RAF mutations. Moreover, for the first time, we have shown that a B
      RAF, MEK and AurkA inhibitor triple drug combination offers increased efficacy
      against melanoma cell growth and might be considered as a potential treatment
      strategy for enhancing clinical response in melanoma. However, although this
      triple drug combination was more effective at the epidermal/dermal junction, the
      suggested presence of alive and proliferating melanoma cells in the dermal
      stratum could result in drug resistance and disease recurrence. Molecular
      characterization of these dermal cells may be critical for the development of
      novel therapeutic strategies.

PMID- 25074439
TI  - Identification and functional characterization of the Arabidopsis Snf1-related
      protein kinase SnRK2.4 phosphatidic acid-binding domain.
AB  - Phosphatidic acid (PA) is an important signalling lipid involved in various
      stress-induced signalling cascades. Two SnRK2 protein kinases (SnRK2.4 and
      SnRK2.10), previously identified as PA-binding proteins, are shown here to prefer
      binding to PA over other anionic phospholipids and to associate with cellular
      membranes in response to salt stress in Arabidopsis roots. A 42 amino acid
      sequence was identified as the primary PA-binding domain (PABD) of SnRK2.4.
      Unlike the full-length SnRK2.4, neither the PABD-YFP fusion protein nor the
      SnRK2.10 re-localized into punctate structures upon salt stress treatment,
      showing that additional domains of the SnRK2.4 protein are required for its re
      localization during salt stress. Within the PABD, five basic amino acids,
      conserved in class 1 SnRK2s, were found to be necessary for PA binding.
      Remarkably, plants overexpressing the PABD, but not a non-PA-binding mutant
      version, showed a severe reduction in root growth. Together, this study
      biochemically characterizes the PA-SnRK2.4 interaction and shows that
      functionality of the SnRK2.4 PABD affects root development. 

PMID- 25074440
TI  - The simplest method for fabrication of high refractive index polymer-metal oxide
      hybrids based on a soap-free process.
AB  - A new method for facile fabrication of high refractive index materials that is
      based on simple blending of polymers and heteropoly acids is demonstrated. This
      hybridization is shown to dramatically increase the refractive index of the
      general polymer, while maintaining a high transparency. 

PMID- 25074442
TI  - Association of IL-21 polymorphisms (rs907715, rs2221903) with susceptibility to
      multiple autoimmune diseases: a meta-analysis.
AB  - OBJECTIVES: Previous published data indicated that interleukin-21 (IL-21) gene
      polymorphisms were shown to associate with multiple autoimmune diseases (ADs),
      but the results remain inconclusive. The aim of this study was to perform a meta
      analysis to assess the overall association between IL-21 gene polymorphisms
      (rs907715, rs2221903) and multiple ADs. METHODS: All eligible case-control
      studies were searched in the PubMed and Embase database. A meta-analysis was
      conducted on the association between the IL-21 gene variants and ADs using: (1)
      allelic contrast, (2) homozygote contrast, (3) the recessive model, and (4) the
      dominant model. RESULTS: A total of 12 relevant studies including 10,535 cases
      and 19,356 controls were enrolled in this meta-analysis. A significant
      association between IL-21 rs907715 gene polymorphism and AD was found under the
      allelic (OR: 1.102, 95% CI: 1.057-1.149, p = 0.000), homozygous (OR: 1.220, 95%
      CI: 1.089-1.368, p = 0.001), dominant (OR: 1.160, 95% CI: 1.027-1.309, p =
      0.017), and recessive genetic model (OR: 1.119, 95% CI: 1.055-1.187, p = 0.000)
      among Caucasian populations. However, there was no significant association
      between IL-21 rs2221903 polymorphism and AD in different genetic models.
      CONCLUSIONS: Data from the present study suggest that the IL-21 rs907715
      polymorphism might be associated with multiple ADs susceptibility in Caucasians.
      Especially, the allele G of intronic rs907715 in IL-21 confers increased risk of
      ADs.

PMID- 25074443
TI  - Evolutionary basis for human language. Comment on "Toward a computational
      framework for cognitive biology: unifying approaches from cognitive neuroscience
      and comparative cognition" by Tecumseh Fitch.

PMID- 25074441
TI  - Approach to assessing determinants of glucose homeostasis in the conscious mouse.
AB  - Obesity and type 2 diabetes lessen the quality of life of those afflicted and
      place considerable burden on the healthcare system. Furthermore, the detrimental
      impact of these pathologies is expected to persist or even worsen. Diabetes is
      characterized by impaired insulin action and glucose homeostasis. This has led to
      a rapid increase in the number of mouse models of metabolic disease being used in
      the basic sciences to assist in facilitating a greater understanding of the
      metabolic dysregulation associated with obesity and diabetes, the identification
      of therapeutic targets, and the discovery of effective treatments. This review
      briefly describes the most frequently utilized models of metabolic disease. A
      presentation of standard methods and technologies on the horizon for assessing
      metabolic phenotypes in mice, with particular emphasis on glucose handling and
      energy balance, is provided. The article also addresses issues related to study
      design, selection and execution of metabolic tests of glucose metabolism, the
      presentation of data, and interpretation of results. 

PMID- 25074444
TI  - Neurochemistry of major depression: a study using magnetic resonance
      spectroscopy.
AB  - RATIONALE: Magnetic resonance spectroscopy (MRS) is an acceptable non-invasive
      means of studying brain neurochemistry in depression. Previous studies in
      depressed patients have focused on measurement of the amino acid
      neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate. OBJECTIVES: The
      aim of this study is to use MRS in conjunction with the ultrashort echo time
      'SPECIAL' technique to measure cortical levels of GABA, glutamate and glutathione
      (GSH) levels in unmedicated patients with major depression. We also examined the
      effect of 6-week treatment with the selective serotonin re-uptake inhibitor,
      escitalopram. METHODS: We studied patients with DSM-IV major depression and
      healthy age-matched controls using proton MRS. GABA, glutamate and GSH were
      measured relative to creatine in a voxel placed in occipital cortex. RESULTS:
      There was no difference in GABA or glutamate levels between depressed
      participants and controls; however, depressed patients had lower GSH levels. Six
      week escitalopram treatment, which resulted in significant clinical responses in
      some patients, did not alter concentrations of GABA, glutamate or GSH.
      CONCLUSIONS: The sources of variability of GABA and glutamate measures in
      different studies of depressed patients require further study. Our results
      suggest that concomitant treatment with selective serotonin re-uptake inhibitors
      (SSRIs) is unlikely to be an important confounding factor. If lowered GSH levels
      can be confirmed, they may represent the presence of oxidative stress in some
      depressed patients.

PMID- 25074446
TI  - 5-HT7 receptor activation: procognitive and antiamnesic effects.
AB  - RATIONALE: The serotonin (5-hydroxytryptamine (5-HT)) 5-HT7 receptor is localized
      in brain areas mediating memory; however, the role of this receptor on memory
      remains little explored. OBJECTIVE: First, demonstrating the associative nature
      of Pavlovian/instrumental autoshaping (P/I-A) task, rats were exposed (three
      sessions) to CS-US (Pavlovian autoshaping), truly random control, free operant,
      and presentations of US or CS, and they were compared with rats trained-tested
      for one session to the P/I-A procedure. Also, effects of the 5-HT7 receptor
      agonist LP-211 administered intraperitoneally after training was determined on
      short- (1.5 h) and long-term memory 24 and 48 h) and on scopolamine-induced
      memory impairment and cAMP production. METHODS: Autoshaping and its behavioral
      controls were studied. Other animals were subjected to an autoshaping training
      session and immediately afterwards were given (intraperitoneal) vehicle or LP-211
      (0.1-10 mg/kg) and/or scopolamine (0.2 mg/kg) and tested for short-term memory
      (STM) and long-term memory (LTM); their brains were extracted for the cAMP ELISA
      immunoassay. RESULTS: P/I-A group produced the higher %CR. LP-211 did not affect
      STM; nonetheless, at 0.5 and 1.0 mg/kg, it improved LTM. The 5-HT7 receptor
      antagonist SB-269970 (SB; 10.0 mg/kg) alone had no effect; nevertheless, the LP
      211 (1.0 mg/kg) LTM facilitation was reversed by SB. The scopolamine (0.2 mg/kg)
      induced-decrement in CR was accompanied by significant increased cAMP production.
      The scopolamine-induced decrement in CR and increments in cAMP were significantly
      attenuated by LP-211. CONCLUSIONS: Autoshaping is a reliable associative learning
      task whose consolidation is facilitated by the 5-HT7 receptor agonist LP-211.

PMID- 25074447
TI  - The BDNF Val(66)Met polymorphism is associated with escitalopram response in
      depressed patients.
AB  - BACKGROUND: The brain-derived neurotrophic factor (BDNF) gene is a candidate gene
      in therapeutic responses to antidepressants. The aim of the study was to
      determine the effects of BDNF allelic variability on responses to escitalopram
      treatment at 3 weeks after treatment initiation and at a 6-week endpoint.
      METHODS: We included 187 Caucasian subjects with depression; 153 completed the 6
      week study. Clinical evaluation was performed using the Montgomery and Asberg
      Depression Rating Scale (MADRS) before and after 3-6 weeks of treatment. RESULTS:
      After 3 weeks of treatment, we saw significantly better treatment responses in
      the Met carriers and greater antidepressant resistance among the Val/Val
      homozygotes. Relative to Val/Val homozygous (59.78 %), a significantly greater
      proportion of subjects Met-carriers (77.94 %) responded to escitalopram treatment
      (chi (2) = 5.88, p = 0.015). After 6 weeks, we found the same pattern of results
      but this effect did not reach statistical significance (chi (2) = 2.07, p =
      0.15). CONCLUSION: These findings highlight a significant association between the
      BDNF valine to methionine substitution (Val(66)Met) polymorphism and the
      treatment response to escitalopram in a Caucasian population of severely
      depressed inpatients.

PMID- 25074448
TI  - A radial flow microfluidic device for ultra-high-throughput affinity-based
      isolation of circulating tumor cells.
AB  - Circulating tumor cells (CTCs) are believed to play an important role in
      metastasis, a process responsible for the majority of cancer-related deaths. But
      their rarity in the bloodstream makes microfluidic isolation complex and time
      consuming. Additionally the low processing speeds can be a hindrance to obtaining
      higher yields of CTCs, limiting their potential use as biomarkers for early
      diagnosis. Here, a high throughput microfluidic technology, the OncoBean Chip, is
      reported. It employs radial flow that introduces a varying shear profile across
      the device, enabling efficient cell capture by affinity at high flow rates. The
      recovery from whole blood is validated with cancer cell lines H1650 and MCF7,
      achieving a mean efficiency >80% at a throughput of 10 mL h(-1) in contrast to a
      flow rate of 1 mL h(-1) standardly reported with other microfluidic devices.
      Cells are recovered with a viability rate of 93% at these high speeds, increasing
      the ability to use captured CTCs for downstream analysis. Broad clinical
      application is demonstrated using comparable flow rates from blood specimens
      obtained from breast, pancreatic, and lung cancer patients. Comparable CTC
      numbers are recovered in all the samples at the two flow rates, demonstrating the
      ability of the technology to perform at high throughputs. 

PMID- 25074450
TI  - Estimation of genomic breeding values for residual feed intake in a multibreed
      cattle population.
AB  - Residual feed intake (RFI) is a measure of the efficiency of animals in feed
      utilization. The accuracies of GEBV for RFI could be improved by increasing the
      size of the reference population. Combining RFI records of different breeds is a
      way to do that. The aims of this study were to 1) develop a method for
      calculating GEBV in a multibreed population and 2) improve the accuracies of GEBV
      by using SNP associated with RFI. An alternative method for calculating
      accuracies of GEBV using genomic BLUP (GBLUP) equations is also described and
      compared to cross-validation tests. The dataset included RFI records and 606,096
      SNP genotypes for 5,614 Bos taurus animals including 842 Holstein heifers and
      2,009 Australian and 2,763 Canadian beef cattle. A range of models were tested
      for combining genotype and phenotype information from different breeds and the
      best model included an overall effect of each SNP, an effect of each SNP specific
      to a breed, and a small residual polygenic effect defined by the pedigree. In
      this model, the Holsteins and some Angus cattle were combined into 1 "breed
      class" because they were the only cattle measured for RFI at an early age (6-9 mo
      of age) and were fed a similar diet. The average empirical accuracy (0.31),
      estimated by calculating the correlation between GEBV and actual phenotypes
      divided by the square root of estimated heritability in 5-fold cross-validation
      tests, was near to that expected using the GBLUP equations (0.34). The average
      empirical and expected accuracies were 0.30 and 0.31, respectively, when the GEBV
      were estimated for each breed separately. Therefore, the across-breed reference
      population increased the accuracy of GEBV slightly, although the gain was greater
      for breeds with smaller number of individuals in the reference population (0.08
      in Murray Grey and 0.11 in Hereford for empirical accuracy). In a second
      approach, SNP that were significantly (P < 0.001) associated with RFI in the beef
      cattle genomewide association studies were used to create an auxiliary genomic
      relationship matrix for estimating GEBV in Holstein heifers. The empirical (and
      expected) accuracy of GEBV within Holsteins increased from 0.33 (0.35) to 0.39
      (0.36) and improved even more to 0.43 (0.50) when using a multibreed reference
      population. Therefore, a multibreed reference population is a useful resource to
      find SNP with a greater than average association with RFI in 1 breed and use them
      to estimate GEBV in another breed. 

PMID- 25074451
TI  - Apparent total tract energy and macronutrient digestibility of one- to three-day
      old, adult ground, extruded, and canned chicken-based diets in domestic cats
      (Felis silvestris catus).
AB  - There has been a recent increase in the popularity of feeding unconventional
      diets, including whole prey diets, to domestic cats (Felis silvestris catus).
      Data are needed that allow animal caretakers to choose and formulate diets that
      meet the nutritional requirements of their cats. Our objective was to evaluate
      the effects of feeding 1- to 3-d-old whole chicks (WHO), ground adult chicken
      product (GRO), a chicken-based canned diet (CAN), and a chicken-based extruded
      diet (EXT) on apparent total tract energy and macronutrient digestibility, N
      balance, and blood metabolites of domestic cats (n = 11). Macronutrient, energy,
      and moisture concentrations of diets varied greatly (e.g., CP: 35 to 72% DM);
      however, cats fed all diets maintained BW and N balance. In general, cats fed WHO
      had lower nutrient digestibility than those fed CAN and EXT. Cats fed GRO had
      greater nutrient digestibility than cats fed commercial diets. For example,
      apparent OM and GE digestibility coefficients were greater (P <= 0.05) for cats
      fed CAN (86 and 88%, respectively), EXT (88 and 88%), and GRO (94 and 95%)
      compared with those fed WHO (83 and 83%) and greater (P <= 0.05) for cats fed GRO
      compared with those fed CAN and EXT. Many blood metabolites were modified by
      diet, but most remained within reference ranges for domestic cats. Serum
      cholesterol was elevated above the reference range for all treatments and greater
      (P <= 0.05) for cats fed WHO compared with those fed CAN, EXT, and GRO. Serum
      creatinine concentrations were above the reference range for all treatments and
      greater (P <= 0.05) for cats fed GRO compared with those fed CAN or WHO. These
      data indicate that the whole prey tested herein maintained short-term health and
      are adequately digestible for use in companion animal diets. Research is needed
      to determine the global and long-term health implications of feeding whole or
      ground diets to domestic cats, which may be different in terms of macronutrient,
      energy, and moisture profiles and nutrient digestibility. 

PMID- 25074449
TI  - Reproduction Symposium: developmental programming of reproductive and metabolic
      health.
AB  - Inappropriate programming of the reproductive system by developmental exposure to
      excess steroid hormones is of concern. Sheep are well suited for investigating
      developmental origin of reproductive and metabolic disorders. The developmental
      time line of female sheep (approximately 5 mo gestation and approximately 7 mo to
      puberty) is ideal for conducting sequential studies of the progression of
      metabolic and/or reproductive disruption from the developmental insult to
      manifestation of adult consequences. Major benefits of using sheep include
      knowledge of established critical periods to target adult defects, a rich
      understanding of reproductive neuroendocrine regulation, availability of
      noninvasive approaches to monitor follicular dynamics, established surgical
      approaches to obtain hypophyseal portal blood for measurement of hypothalamic
      hormones, and the ability to perform studies in natural setting thereby keeping
      behavioral interactions intact. Of importance is the ability to chronically
      instrument fetus and mother for determining early endocrine perturbations.
      Prenatal exposure of the female to excess testosterone (T) leads to an array of
      adult reproductive disorders that include LH excess, functional hyperandrogenism,
      neuroendocrine defects, multifollicular ovarian morphology, and corpus luteum
      dysfunction culminating in early reproductive failure. At the neuroendocrine
      level, all 3 feedback systems are compromised. At the pituitary level,
      gonadotrope (LH secretion) sensitivity to GnRH is increased. Multifollicular
      ovarian morphology stems from persistence of follicles as well as enhanced
      follicular recruitment. These defects culminate in progressive loss of cyclicity
      and reduced fecundity. Prenatal T excess also leads to fetal growth retardation,
      an early marker of adult reproductive and metabolic diseases, insulin resistance,
      hypertension, and behavioral deficits. Collectively, the reproductive and
      metabolic deficits of prenatal T-treated sheep provide proof of concept for the
      developmental origin of fertility and metabolic disorders. Studies with the
      environmental endocrine disruptor bisphenol A (BPA) show that reproductive
      disruptions found in prenatal BPA-treated sheep are similar to those seen in
      prenatal T-treated sheep. The ubiquitous exposure to endocrine disrupting
      compounds with steroidogenic potential via the environment and food sources calls
      for studies addressing the impact of developmental exposure to environmental
      steroid mimics on reproductive function. 

PMID- 25074452
TI  - Evaluating lysine requirements of nursery pigs fed low protein diets with
      different sources of nonessential amino acids.
AB  - The Lys requirement of nursery pigs may be dependent on the source of
      nonessential AA (NEAA) nitrogen or the source of Lys itself. However, little peer
      reviewed data examines these phenomena. The objectives of these experiments were
      to determine if the Lys requirement of pigs is altered when 1) low protein diets
      are supplemented with different sources of NEAA nitrogen or 2) Lys is supplied as
      a crystalline source instead of intact protein such as soybean meal (SBM). Two 14
      d experiments were conducted using 450 (Exp. 1) and 540 (Exp. 2) pigs (PIC
      C22/C29 * 337). There were 10 treatments in each experiment, each aligned as a 2
      * 5 factorial. In Exp. 1, there were 2 sources of NEAA (l-Gln + l-Gly or l-Gly +
      l-Ala + l-Pro + l-His) and 5 levels of Lys (1.2, 1.3, 1.4, 1.5, and 1.6%). In
      Exp. 2, there were 2 sources of proteins providing additional Lys (l-Lys HCl or
      SBM) and the same 5 levels of Lys. Following weaning at 18 to 22 d of age, pigs
      were fed a common starter diet for 5 d postweaning followed by a 14-d treatment
      period. Pigs were weighed and feed disappearance determined on d 0, 7, and 14 of
      the experiment. Data were analyzed using the MIXED and NLIN procedures of SAS
      (SAS Inst., Cary, NC). In Exp. 1, increasing CP and Lys resulted in a quadratic
      increase (P < 0.05) in ADG and a linear improvement (P < 0.05) in G:F during the
      14-d treatment period. Breakpoint regression analyses revealed that optimum ADG
      was obtained at 1.36% Lys, while optimum G:F was obtained at 1.45% Lys. The
      source of NEAA did not affect (P > 0.10) growth performance during the treatment
      period. In Exp. 2, both ADG and G:F increased linearly (P < 0.05) with increasing
      Lys. Optimal ADG was obtained at 1.47% Lys, but the breakpoint for optimum G:F
      was above tested levels. Source of Lys did not affect (P > 0.10) ADG, but pigs
      fed additional Lys from crystalline sources had improved (P < 0.05) G:F than
      those fed additional Lys from intact protein at 1.50% Lys; however, the analyzed
      Lys values at this level differ. Overall, these data show that the standardized
      ileal digestibility Lys requirement of pigs is not altered when low protein diets
      are supplemented with different sources of NEAA nitrogen. Feed efficiency appears
      to be maximized when additional Lys is supplied by l-Lys HCl instead of SBM, but
      more research is needed to confirm this phenomenon. 

PMID- 25074453
TI  - Pressure load on specific body areas of gestating sows lying on rubber mats with
      different softness.
AB  - Rubber mats offer a possibility to increase lying comfort for sows with positive
      effects on sow lying behavior and health. However, until now, no information has
      been reported about the relationship between the softness of rubber mats and the
      pressure load on certain body areas of sows. We used a total of 68 (40
      multiparous, 28 primiparous) German Landrace * German Landrace sows with a BW
      within the range of 90 to 330 kg (divided in 3 weight classes) to measure peak
      force and distribution of pressure during lying in the sternal and half recumbent
      position. Measures were done in an experimental pen that was equipped with a
      pressure sensor map system (5400 NTL; Tekscan Inc., Boston, MA). Three rubber
      mats differing in softness (penetration depth: hard mat, 4.0 mm [HM]; soft mat,
      14.6 mm [SM]; very soft mat, 43.0 mm [VSM]) were tested and compared to concrete
      floor (CF) as a reference. Pressure load was analyzed in the sternal position for
      the sternum, belly, and ham body regions and also in the half recumbent position
      for the shoulder. For each lying position we determined the body region with the
      highest pressure load and analyzed the peak force (PF) and the contact area (CA)
      using a mixed model ANOVA (MIXED procedure of SAS Enterprise, version 4.3., SAS
      Inst. Inc., Cary, NC) with floor type, weight class of sows, and their
      interaction as fixed factors. Overall, the highest values for PF in the sternal
      position were found on the sternum (median: 1.62 N/cm(2)) and in the half
      recumbent position on the shoulder (median: 2.72 N/cm(2)). In the sternal
      position PF on the sternum was lower on VSM compared to CF (P = 0.001). In the
      half-recumbent position PF on the shoulder was lower on VSM compared to CF (P =
      0.013) and compared to HM (P = 0.011). The weight of the sows affected PF on the
      sternum in the sternal position, with lower values in weight class 1 compared to
      weight class 2 (P = 0.001) and weight class 3 (P = 0.002). Contact area under the
      sternum was larger on SM (P = 0.016) and VSM (P = 0.008) compared to CF in the
      sternal position, and this was affected by weight class (P = 0.0002). In the half
      recumbent position floor type did not affect CA under the shoulder, but CA was
      larger in weight classes 2 and 3 compared to weight class 1 (all P < 0.05).
      Assuming that a reduced PF in combination with pressure distributed over a larger
      area will increase lying comfort, hard rubber mats do not seem to offer a high
      lying comfort with regard to pressure load on debited body regions such as the
      sternum or shoulder. 

PMID- 25074454
TI  - Production performance, carcass composition, and adipose tissue traits of heavy
      pigs: influence of breed and production system.
AB  - Both breed and production systems are responsible for production efficiency and
      quality traits of pork. Effects of breed and production system within breed on
      growth, body fatness, and adipose tissues traits were assessed in the pure Basque
      (B, nonselected, local French) and conventional Large White (LW) breeds, reared
      either in a conventional (C, slatted floor), alternative (A, indoor straw bedding
      and outdoor area), or extensive (E, free range) system. A total of 100 castrated
      males were produced in 2 replicates, each involving 50 pigs distributed in 5
      treatments based on breed and production system (i.e., BC, BA, BE, LWC, and LWA
      [10 pigs/group and per replicate]). From 35 kg BW to slaughter at around 145 kg
      BW, the BC, BA, LWC, and LWA pigs received the same growing and finishing diets,
      whereas the BE pigs had free access to the natural resources of the E pen and
      received a standard growing-finishing diet at restricted allowance according to
      the farming practices of the B pork chain. The B pigs had lower (P < 0.001) ADG
      and G:F than the LW pigs and were much older (P < 0.001) at slaughter. The LWA
      pigs had similar ADG but lower (P = 0.03) G:F than the LWC. Within the B breed,
      the BA had higher (P = 0.04) and the BE lower (P < 0.001) ADG compared with BC
      pigs. The B pigs had a higher (P < 0.001) carcass dressing an exhibited around 2
      fold higher (P < 0.001) back fat proportion, perirenal fat weight and LM lipid
      content than the LW pigs. Compared with C, the A system decreased (P = 0.04)
      carcass dressing within LW but did not influence carcass traits within B pigs.
      The E system decreased (P <= 0.05) carcass dressing, back fat proportion, and LM
      lipid content in BE compared with BC pigs. The B pigs exhibited larger (P <
      0.001) adipocytes in both subcutaneous adipose tissue (SCAT) and LM than the LW
      pigs. Malic enzyme activity was higher in SCAT of B than LW pigs despite their
      greater fatness, and was higher (P <= 0.01) in BA but lower (P < 0.001) in BE
      than in BC pigs. The B pigs had higher (P < 0.001) MUFA but lower (P <= 0.006)
      SFA and PUFA fatty acid percentages in SCAT than the LW pigs. Compared with C,
      the A system had scarce influence on FA composition within each breed, whereas
      the E system led to lower (P = 0.015) SFA and greater (P < 0.001) PUFA in SCAT of
      the B pigs. Altogether, the E production system can counteract the genetic
      potential of B pigs for growth rate but also body fatness. 

PMID- 25074455
TI  - Optimal management of replacement heifers in a beef herd: a model for
      simultaneous optimization of rearing and breeding decisions.
AB  - The aim of this study was to provide farmers an efficient tool for supporting
      optimal decisions in the beef heifer rearing process. The complexity of beef
      heifer management prompted the development of a model including decisions on the
      feeding level during prepuberty (age <10 mo), the time of weaning (age, BW,
      calendar month), the feeding level during the reproductive period (age >=10 mo),
      and time of breeding (age, BW, and calendar month). The model was formulated as 3
      level hierarchic Markov process. A founder level of the model has 12 states
      resembling all possible birth months of a heifer. Based on the birth month
      information from the founder level, for the indoor season (November to April) and
      outdoor season (May to October), feeding and breeding costs (natural service cost
      in the outdoor and AI cost in the indoor season) were applied. The optimal
      rearing strategy was found by maximizing the total discounted net revenues from
      the predicted future productivity of the Polish Limousine heifers defined as the
      cumulative BW of calves born from a cow calved until the age of 5 yr,
      standardized on the 210th day of age. According to the modeled optimal policy,
      heifers fed during the whole rearing period at the ADG of 810 g/d and generally
      weaned after the maximum suckling period of 9 mo should already be bred at the
      age of 13.2 mo and BW constituting 55.6% of the average mature BW. Based on the
      optimal strategy, 52% of all heifers conceived from May to July and calved from
      February to April. This optimal rearing pattern resulted in an average net return
      of EUR 311.6 per pregnant heifer. It was found that the economic efficiency of
      beef operations can be improved by applying different herd management practices
      to those currently used in Poland. Breeding at 55.6% of the average mature BW,
      after a shorter and less expensive rearing period, resulted in an increase in the
      average net return per heifer by almost 18% compared to the conventional system,
      in which heifers were bred after attaining 65% of the mature BW. Extension of the
      rearing period by 2.5 mo (breeding at the age 15.7 mo), due to a prepubertal
      growth rate lowered by 200 g, reduced the average net return per heifer by 6.2%
      compared to the results obtained under the basic model assumptions. In the
      future, the model may also be extended to investigate additional aspects of the
      beef heifer development, such as the environmental impacts of various heifer
      management decisions. 

PMID- 25074456
TI  - The corneous layer of the claw in the lizard Anolis carolinensis mainly contains
      the glycine-cysteine-rich beta-protein HgGC3 in addition to hard keratins.
AB  - The localization of specific claw beta-proteins among the 40 total corneous beta
      proteins present in the lizard Anolis carolinensis is not known. The hardness of
      claws likely depends on glycine-cysteine-rich beta-proteins content, as suggested
      by previous immunoblot studies. Previous studies have indicated that glycine
      cysteine-rich corneous beta-proteins in addition to cysteine-rich alpha-keratins
      are present in the claw. In order to detect at the ultrastructural level the
      presence of claw-specific corneous proteins immunofluorescence and electron
      microscopy immunogold have been utilized. More intense immunoreactivity is
      obtained for the HgGC3 beta-protein while less intense immunolabeling is seen for
      HgGC10 and HgG5 beta-proteins and no labeling for the cysteine-rich beta-protein
      HgC1. The HgGC3 beta-protein appears the prevalent type present in the claw and
      its numerous cysteines likely form intermolecular disulphide bonds while glycine
      contributes hydrophobic properties to the corneous material. Other antibodies
      tagging the core-box and pre-core box regions of beta-proteins label with less
      intensity the corneous layer. The presence of cysteine-rich alpha-keratins with
      high homology to some human hair keratins in the dorsal part of the claw suggests
      that HgGC3-like beta-proteins form numerous disulphide bonds with the larger
      alpha-keratins giving rise to the hard corneous material of the claw.

PMID- 25074457
TI  - Enhanced production of Thermomyces lanuginosus lipase in Pichia pastoris via
      genetic and fermentation strategies.
AB  - This study attempted to enhance the expression level of Thermomyces lanuginosus
      lipase (TLL) in Pichia pastoris using a series of strategies. The tll gene was
      first inserted into the expression vector pPIC9 K and transformed into P.
      pastoris strain GS115. The maximum hydrolytic activity of TLL reached 4,350 U/mL
      under the optimal culture conditions of a 500 mL shaking flask containing 20 mL
      culture medium with the addition of 1.2 % (w/v) methanol, cultivation for 144 h
      at pH 7.0 and 27  degrees C. To further increase the TLL expression and copy
      number, strains containing two plasmids were obtained by sequential
      electroporation into GS115/9k-TLL #3 with a second vector, either pGAPZalphaA
      TLL, pFZalpha-TLL, or pPICZalphaA-TLL. The maximum activity of the resultant
      strains GS115/9KTLL-ZalphaATLL #40, GS115/9KTLL-FZalphaATLL #46 and GS115/9KTLL
      GAPTLL #45 was 6,600 U/mL, 6,000 U/mL and 4,800 U/mL, respectively. The tll copy
      number in these strains, as assessed by real-time quantitative PCR, was
      demonstrated to be seven, five, and three, respectively, versus two copies in
      GS115/9k-TLL #3. When a co-feeding strategy of sorbitol/methanol was adopted in a
      3-L fermenter, the maximum TLL activity of GS115/9k-TLL #3 increased to 27,000
      U/mL after 130 h of fed-batch fermentation, whereas, the maximum TLL activity was
      19,500 U/mL after 145 h incubation when methanol was used as the sole carbon
      source. 

PMID- 25074458
TI  - Capillary instability of axisymmetric, active liquid crystal jets.
AB  - We study linear stability of an infinitely long, axisymmetric, cylindrical active
      liquid crystal (ALC) jet in a passive isotropic fluid matrix using a polar active
      liquid crystal (ALC) model. We identify three possible unstable modes (or
      mechanisms) as the result of the interaction between the flow and the active (or
      self-propelled) molecular motion. The first unstable mode is related to the
      polarity vector instability when coupled to the flow field in the presence of the
      molecular activity. It can be traced back to the inherent polarity vector
      instability in a bulk active liquid crystal flow. However, it can be grossly
      amplified in the ALC jet to encompass up to infinitely many unstable growth rates
      when the long range distortional elastic interaction is weak in certain parameter
      regimes; it can also be suppressed in other parameter regimes completely. The
      second unstable mode is related to the classical capillary or Rayleigh
      instability, which exists in a finite wave interval [0, k(cutoff)]. The new
      feature for this instability lies in the dependence of the cutoff wave number
      (k(cutoff)) on the activity of the active matter system. For ALC jets with
      sufficiently strong contractile activity, the instability can be completely
      suppressed though. The third unstable mode is due to the active viscous stress.
      This unstable mode can emerge in the intermediate wave number regime at a
      sufficiently strong active viscosity and even expand all the way to the zero wave
      number limit when the Rayleigh unstable mode is absent. It can also be suppressed
      in the regime of weak active viscous stress. At any given values of the model
      parameters, the three types of instabilities can show up either individually or
      in a certain combination, or be completely suppressed altogether. In this paper,
      we discuss the positive growth rates associated with the instabilities, windows
      of instability and their dependence on model parameters through extensive
      numerical computations aided by asymptotic analyses.

PMID- 25074459
TI  - Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant
      EGFR-mutant lung cancer with and without T790M mutations.
AB  - EGFR-mutant lung cancers responsive to reversible EGFR inhibitors
      (gefitinib/erlotinib) develop acquired resistance, mediated by second-site EGFR
      T790M mutation in >50% of cases. Preclinically, afatinib (irreversible ErbB
      family blocker) plus cetuximab (anti-EGFR monoclonal antibody) overcomes T790M
      mediated resistance. This phase Ib study combining afatinib and cetuximab
      enrolled heavily pretreated patients with advanced EGFR-mutant lung cancer and
      acquired resistance to erlotinib/gefitinib. Patients provided post-acquired
      resistance tumor samples for profiling EGFR mutations. Among 126 patients,
      objective response rate (overall 29%) was comparable in T790M-positive and T790M
      negative tumors (32% vs. 25%; P = 0.341). Median progression-free survival was
      4.7 months (95% confidence interval, 4.3-6.4), and the median duration of
      confirmed objective response was 5.7 months (range, 1.8-24.4). Therapy-related
      grade 3/4 adverse events occurred in 44%/2% of patients. Afatinib-cetuximab
      demonstrated robust clinical activity and a manageable safety profile in EGFR
      mutant lung cancers with acquired resistance to gefitinib or erlotinib, both with
      and without T790M mutations, warranting further investigation. SIGNIFICANCE: This
      article reports the results of a trial combining afatinib and cetuximab in
      patients with acquired resistance and details the first clinical proof-of-concept
      for the preclinical hypothesis that a significant proportion of tumors in
      patients with acquired resistance to gefitinib/erlotinib remain dependent on EGFR
      signaling for survival.

PMID- 25074460
TI  - Neurofibromatosis type 1 molecular diagnosis: what can NGS do for you when you
      have a large gene with loss of function mutations?
AB  - Molecular diagnosis of neurofibromatosis type 1 (NF1) is challenging owing to the
      large size of the tumour suppressor gene NF1, and the lack of mutation hotspots.
      A somatic alteration of the wild-type NF1 allele is observed in NF1-associated
      tumours. Genetic heterogeneity in NF1 was confirmed in patients with SPRED1
      mutations. Here, we present a targeted next-generation sequencing (NGS) of NF1
      and SPRED1 using a multiplex PCR approach (230 amplicons of ~150 bp) on a PGM
      sequencer. The chip capacity allowed mixing 48 bar-coded samples in a 4-day
      workflow. We validated the NGS approach by retrospectively testing 30 NF1-mutated
      samples, and then prospectively analysed 279 patients in routine diagnosis. On
      average, 98.5% of all targeted bases were covered by at least 20X and 96% by at
      least 100X. An NF1 or SPRED1 alteration was found in 246/279 (88%) and 10/279
      (4%) patients, respectively. Genotyping throughput was increased over 10 times,
      as compared with Sanger, with ~90[euro ] for consumables per sample.
      Interestingly, our targeted NGS approach also provided quantitative information
      based on sequencing depth allowing identification of multiexons deletion or
      duplication. We then addressed the NF1 somatic mutation detection sensitivity in
      mosaic NF1 patients and tumours. 

PMID- 25074461
TI  - Genomic aberrations of the CACNA2D1 gene in three patients with epilepsy and
      intellectual disability.
AB  - Voltage-gated calcium channels have an important role in neurotransmission.
      Aberrations affecting genes encoding the alpha subunit of these channels have
      been associated with epilepsy and neuropsychiatric disorders such as autism or
      schizophrenia. Here we report three patients with a genomic aberration affecting
      the CACNA2D1 gene encoding the alpha2delta subunit of these voltage-gated calcium
      channels. All three patients present with epilepsy and intellectual disability
      pinpointing the CACNA2D1 gene as an interesting candidate gene for these clinical
      features. Besides these characteristics, patient 2 also presents with obesity
      with hyperinsulinism, which is very likely to be caused by deletion of the CD36
      gene. 

PMID- 25074463
TI  - Dietary fat quality impacts genome-wide DNA methylation patterns in a cross
      sectional study of Greek preadolescents.
AB  - The type and the amount of dietary fat have a significant influence on the
      metabolic pathways involved in the development of obesity, metabolic syndrome,
      diabetes type 2 and cardiovascular diseases. However, it is unknown to what
      extent this modulation is achieved through DNA methylation. We assessed the
      effects of cholesterol intake, the proportion of energy intake derived from fat,
      the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA),
      the ratio of monounsaturated fatty acids (MUFA) to SFA, and the ratio of
      MUFA+PUFA to SFA on genome-wide DNA methylation patterns in normal-weight and
      obese children. We determined the genome-wide methylation profile in the blood of
      69 Greek preadolescents (~10 years old) as well as their dietary intake for two
      consecutive weekdays and one weekend day. The methylation levels of one CpG
      island shore and four sites were significantly correlated with total fat intake.
      The methylation levels of 2 islands, 11 island shores and 16 sites were
      significantly correlated with PUFA/SFA; of 9 islands, 26 island shores and 158
      sites with MUFA/SFA; and of 10 islands, 40 island shores and 130 sites with
      (MUFA+PUFA)/SFA. We found significant gene enrichment in 34 pathways for
      PUFA/SFA, including the leptin pathway, and a significant enrichment in 5
      pathways for (MUFA+PUFA)/SFA. Our results suggest that specific changes in DNA
      methylation may have an important role in the mechanisms involved in the
      physiological responses to different types of dietary fat. 

PMID- 25074464
TI  - A mixed methods exploration of families' experiences of the diagnosis of
      childhood spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease
      with a carrier frequency of 1 in 41 in Australia. Childhood SMA is classified
      into three types based on the age at which children present with symptoms and the
      clinical severity. Families' experiences leading up to the diagnosis have not
      been described, but are important when considering the potential for a diagnostic
      odyssey. Using a mixed methods approach, data were collected from interviews and
      a national survey of families of children with SMA to explore their experiences
      of this journey. The combined findings (n=28) revealed that the journey to
      receiving a diagnosis was protracted. The time from first noticing symptoms to
      finally receiving a diagnosis was emotional and frustrating. Once parents or
      other family members became aware of symptoms, almost all had consulted with
      multiple different health professionals before the diagnosis was ultimately made.
      Not surprisingly, receiving the diagnosis was devastating to the families. The
      nature of the information and the way it was given to them was not always
      optimal, particularly because of the difficulties predicting clinical severity.
      Most felt that their child could have been diagnosed earlier and, although there
      were mixed views around the benefit of this for their child, they felt it may
      have reduced the emotional impact on families. Overall, families were more in
      favour of population carrier screening for SMA when compared with newborn
      screening of the population. Despite an increasing awareness of SMA, the
      diagnostic delay continues to have negative impacts on families. 

PMID- 25074462
TI  - Echoes from Sepharad: signatures on the maternal gene pool of crypto-Jewish
      descendants.
AB  - The majority of genetic studies on Jewish populations have been focused on
      Ashkenazim, and genetic data from the Sephardic original source, the Iberian
      Peninsula, are particularly scarce. Regarding the mitochondrial genome, the
      available information is limited to a single Portuguese village, Belmonte, where
      just two different lineages (a single one corresponding to 93.3%) were found in
      30 individuals. Aiming at disclosing the ancestral maternal background of the
      Portuguese Jewry, we enlarged the sampling to other crypto-Jewish descendants in
      the Braganca district (NE Portugal). Fifty-seven complete mtDNA genomes were
      newly sequenced and - in contrast with Belmonte - a high level of diversity was
      found, with five haplogroups (HV0b, N1, T2b11, T2e and U2e) being putatively
      identified as Sephardic founding lineages. Therefore - in sharp contrast with
      Belmonte - these communities have managed to escape the expected inbreeding
      effects caused by centuries of religious repression and have kept a significant
      proportion of the Sephardic founder gene pool. This deeper analysis of the
      surviving Sephardic maternal lineages allowed a much more comprehensive and
      detailed perspective on the origins and survival of the Sephardic genetic
      heritage. In line with previously published results on Sephardic paternal
      lineages, our findings also show a surprising resistance to the erosion of
      genetic diversity in the maternal lineages. 

PMID- 25074465
TI  - Identification of previously unrecognized FAP in children with Gardner fibroma.
AB  - Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner
      fibroma, may occur sporadically or as a result of inherited predisposition (as
      part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis
      often present beta-catenin overexpression (by activating CTNNB1 somatic variants
      or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma
      are unknown. We characterized in detail Gardner fibromas diagnosed in two infants
      to evaluate their role as sentinel lesions of previously unrecognized FAP. In the
      first infant we found a 5q deletion including APC in the tumor and the novel APC
      variant c.4687dup in constitutional DNA. In the second infant we found the
      c.5826_5829del and c.1678A>T APC variants in constitutional and tumor DNA,
      respectively. None of the constitutional APC variants occurred de novo and both
      tumors showed nuclear staining for beta-catenin and no CTNNB1 variants. We
      present the first comprehensive characterization of the pathogenetic mechanisms
      of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP
      families. 

PMID- 25074466
TI  - Scientists' perspectives on consent in the context of biobanking research.
AB  - Most bioethics studies have focused on capturing the views of patients and the
      general public on research ethics issues related to informed consent for
      biobanking and only a handful of studies have examined the perceptions of
      scientists. Capturing the opinions of scientists is important because they are
      intimately involved with biobanks as collectors and users of samples and health
      information. In this study, we performed interviews with scientists followed by
      qualitative analysis to capture the diversity of perspectives on informed
      consent. We found that the majority of scientists in our study reported their
      preference for a general consent approach although they do not believe there to
      be a consensus on consent type. Despite their overall desire for a general
      consent model, many reported several concerns including donors needing some form
      of assurance that nothing unethical will be done with their samples and
      information. Finally, scientists reported mixed opinions about incorporating
      exclusion clauses in informed consent as a means of limiting some types of
      contentious research as a mechanism to assure donors that their samples and
      information are being handled appropriately. This study is one of the first to
      capture the views of scientists on informed consent in biobanking. Future studies
      should attempt to generalize findings on the perspectives of different scientists
      on informed consent for biobanking. 

PMID- 25074467
TI  - Phenome-wide association studies (PheWASs) for functional variants.
AB  - The genome-wide association study (GWAS) is a powerful approach for studying the
      genetic complexities of human disease. Unfortunately, GWASs often fail to
      identify clinically significant associations and describing function can be a
      challenge. GWAS is a phenotype-to-genotype approach. It is now possible to
      conduct a converse genotype-to-phenotype approach using extensive electronic
      medical records to define a phenome. This approach associates a single genetic
      variant with many phenotypes across the phenome and is called a phenome-wide
      association study (PheWAS). The majority of PheWASs conducted have focused on
      variants identified previously by GWASs. This approach has been efficient for
      rediscovering gene-disease associations while also identifying pleiotropic
      effects for some single-nucleotide polymorphisms (SNPs). However, the use of SNPs
      identified by GWAS in a PheWAS is limited by the inherent properties of the GWAS
      SNPs, including weak effect sizes and difficulty when translating discoveries to
      function. To address these challenges, we conducted a PheWAS on 105 presumed
      functional stop-gain and stop-loss variants genotyped on 4235 Marshfield Clinic
      patients. Associations were validated on an additional 10 640 Marshfield Clinic
      patients. PheWAS results indicate that a nonsense variant in ARMS2 (rs2736911) is
      associated with age-related macular degeneration (AMD). These results demonstrate
      that focusing on functional variants may be an effective approach when conducting
      a PheWAS. 

PMID- 25074468
TI  - Probing the effects of experimental conditions on the character of drug-polymer
      phase diagrams constructed using Flory-Huggins theory.
AB  - PURPOSE: Amorphous drug-polymer solid dispersions have been found to result in
      improved drug dissolution rates when compared to their crystalline counterparts.
      However, when the drug exists in the amorphous form it will possess a higher
      Gibb's free energy than its associated crystalline state and can recrystallize.
      Drug-polymer phase diagrams constructed through the application of the Flory
      Huggins (F-H) theory contain a wealth of information regarding thermodynamic and
      kinetic stability of the amorphous drug-polymer system. This study was aimed to
      evaluate the effects of various experimental conditions on the solubility and
      miscibility detections of drug-polymer binary system. METHODS: Felodipine (FD)
      Polyvinylpyrrolidone (PVP) K15 (PVPK15) and FD-Polyvinylpyrrolidone/vinyl acetate
      (PVP/VA64) were the selected systems for this research. Physical mixtures with
      different drug loadings were mixed and ball milled. These samples were then
      processed using Differential Scanning Calorimetry (DSC) and measurements of
      melting point (Tend) and glass transition (Tg) were detected using heating rates
      of 0.5, 1.0 and 5.0 degrees C/min. RESULTS: The melting point depression data was
      then used to calculate the F-H interaction parameter (chi) and extrapolated to
      lower temperatures to complete the liquid-solid transition curves. The
      theoretical binodal and spinodal curves were also constructed which were used to
      identify regions within the phase diagram. The effects of polymer selection, DSC
      heating rate, time above parent polymer Tg and polymer molecular weight were
      investigated by identifying amorphous drug miscibility limits at pharmaceutically
      relevant temperatures. CONCLUSION: The potential implications of these findings
      when applied to a non-ambient processing method such as Hot Melt Extrusion (HME)
      are also discussed.

PMID- 25074469
TI  - Co-spray dried carbohydrate microparticles: crystallisation delay/inhibition and
      improved aerosolization characteristics through the incorporation of
      hydroxypropyl-beta-cyclodextrin with amorphous raffinose or trehalose.
AB  - PURPOSE: To formulate and investigate the physicochemical properties, physical
      stability and aerosolization characteristics of nanoporous/nanoparticulate
      microparticles (NPMPs) prepared by co-spray drying the sugars raffinose
      pentahydrate (R) or trehalose dihydrate (T) with the cyclic oligosaccharide
      hydroxypropyl-beta-cyclodextrin (HPbetaCD). METHODS: Production of powders was
      carried out using a laboratory scale spray dryer. The resulting powders were
      characterised by X-ray powder diffraction (XRPD), scanning electron microscopy
      (SEM), laser diffraction particle sizing, specific surface area analysis (SSA),
      Fourier transform infrared (FTIR), differential scanning calorimetry (DSC),
      dynamic vapour sorption (DVS) and aerodynamic assessment using a Next Generation
      Impactor (NGI). RESULTS: Powders were amorphous and composed of spherical, porous
      microparticles with reduced particle size and high specific surface area (~100
      m(2)/g). DSC scans showed a single glass transition temperature. FTIR was
      indicative of the existence of molecular interactions between the carbohydrates.
      DVS analysis showed an increase in the critical relative humidity (RH) of
      raffinose and trehalose and eventual crystallization inhibition with increasing
      concentration of HPbetaCD. The in vitro deposition showed powders formulated with
      HPbetaCD had higher recovered emitted dose and fine particle fraction (<5 MUm)
      than raffinose and trehalose spray dried alone. CONCLUSIONS: The co-spray drying
      of raffinose or trehalose with HPbetaCD results in powders with improved
      physicochemical characteristics, physical stability and aerodynamic behaviour
      compared to spray-dried raffinose/trehalose particles, constituting improved
      potential drug-carrier systems for pulmonary delivery.

PMID- 25074471
TI  - CXCR4 dysfunction in non-alcoholic steatohepatitis in mice and patients.
AB  - Homing of inflammatory cells to the liver is key in the progression of non
      alcoholic steatohepatitis (NASH). An abnormal response of CD4+ T-cells from obese
      mice to the chemotactic effect of CXCL12 has been reported but the mechanism
      involved in this process and relevance in patients are unknown. We aimed to
      explore the mechanism involved in the abnormal chemotaxis of CXC chemokine ligand
      12 (CXCL12) in several mouse models of NASH and the relevance in the context of
      human non-alcoholic fatty liver disease (NAFLD). We assessed chemotactic
      responsiveness of CD4+ T-cells to CXCL12, the effect of AMD3100, a CXC chemokine
      receptor 4 (CXCR4) antagonist, in mice and lymphocytes from patients with NAFLD,
      and the affinity of CXCL12 for CXCR4. CXCL12-promoted migration of CD4+ T-cells
      from three different mouse models of NASH was increased and dependent of CXCR4.
      CD4+ T-cells from patients with NASH, but not from patients with pure steatosis,
      responded more strongly to the chemotactic effect of CXCL12, and this response
      was inhibited by AMD3100. Treatment with AMD3100 decreased the number of CD4+ T
      cells to the liver in ob/ob mice. CXCL12 expression in the liver, CXCR4 and CXCR7
      expression in CD4+ T-cells were not increased in three different mouse models of
      NASH. However, the affinity of CXCL12 for CXCR4 was increased in CD4+ T-cells of
      ob/ob mice. In conclusion, the CXCL12/CXCR4 pathway contributes in both mice and
      patients to the enhanced recruitment of CD4+ T-cells in NASH. An increased
      affinity of CXCL12 to CXCR4 rather than a higher expression of the chemokine or
      its receptors is involved in this process. 

PMID- 25074470
TI  - Observation of the middle intestinal tight junction structure, cloning and
      studying tissue distribution of the four Claudin genes of the grass carp
      (Ctenopharyngodon idellus).
AB  - To confirm the existence of the tight junction (TJ) in middle intestine and
      obtain the genetic information of Claudin-3, Claudin-15a, Claudinb and Claudinc
      of grass carp, we observed the physical structure of TJ by transmission electron
      microscopy and cloned the partial cDNAs of the four Claudins using reverse
      transcriptase PCR technique. The four partial cDNAs consist of 1,261, 490, 776
      and 662 bp encoded 131, 150, 195 and 171 amino acids, respectively. Homology
      analysis showed that the grass carp Claudin shared high homology with other
      teleost species, especially with Danio rerio and Carassius auratus. Multi
      alignments of the four Claudin amino acid sequences have seen the two conserved
      cysteines existing in the first extracellular loop of Claudin-15a, Claudinb and
      Claudinc, and the sequence diversity of the four Claudins mainly lies within the
      C-terminal tails, which usually end with the -Y-V motif, except the -F-V motif in
      Claudinb. Tissue distributions of the four Claudins were measured by applying
      quantitative real-time PCR technique. Results showed that Claudin-3 was mainly
      expressed in liver and middle intestine and Claudinb was ubiquitously expressed
      with a higher expression in middle intestine while Claudin-15a and Claudinc were
      mainly expressed in middle intestine. Our study revealed the existence of the TJ
      in the middle intestinal and obtained the genetic information of Claudin-3,
      Claudin-15a, Claudinb and Claudinc of grass carp, aiming to found the molecular
      biology basis for the further study of the intestinal barrier function of grass
      carp. 

PMID- 25074472
TI  - Cardiovascular risk and acute coronary syndrome in giant cell arteritis: a
      population-based retrospective cohort study.
AB  - OBJECTIVE: To assess the occurrence of acute coronary syndrome (ACS) in patients
      with giant cell arteritis (GCA) compared to subjects without GCA. METHODS: We
      retrospectively reviewed a population-based incidence cohort of Olmsted County,
      Minnesota residents with GCA diagnosed in 1950-2009. We compared this cohort with
      a cohort of patients without GCA of similar age, sex, and calendar year from the
      same population. RESULTS: The study included 245 patients with GCA and 245 non
      GCA subjects. The mean +/- SD Framingham cardiovascular risk score was 30% +/-
      19% in GCA patients and 34% +/- 23% in non-GCA subjects (P = 0.096) at the
      incidence/index date. Diabetes mellitus was significantly less common in GCA
      patients than non-GCA subjects at the index date. The mean high-density
      lipoprotein was higher and triglycerides were lower, with fewer patients taking
      lipid-lowering medications in the GCA cohort compared to the non-GCA cohort at
      the index date. During followup, no difference between the 2 cohorts was noted in
      the overall rate of ACS events (hazard ratio 0.74, 95% confidence interval 0.44
      1.26). Overall thrombosis in myocardial infarction scores were similar in both
      cohorts. Revascularization procedures were done less frequently in GCA than in
      non-GCA subjects (19% versus 50%; P = 0.015). Post-ACS hospital length of stays
      and complications were similar in both cohorts. CONCLUSION: Multiple
      cardiovascular risk factors are less atherogenic at incidence of GCA. There is no
      overall increased risk of ACS in patients with GCA.

PMID- 25074473
TI  - Effect of surface stiffness on the neural control of stretch-shortening cycle
      movements.
AB  - AIM: It is accepted that leg stiffness (Kleg ) increases when surface stiffness
      decreases, and vice versa. However, little is known how the central nervous
      system fulfils this task. To understand the effect of surface stiffness on the
      neural control of stretch-shortening cycle movements, this study aimed to compare
      modulation of spinal and corticospinal excitability at distinct phases after
      ground contact during two-legged hopping when changing from solid to elastic
      ground. METHODS: Motor-evoked potentials (MEPs) induced by transcranial magnetic
      stimulation (TMS) and H-reflexes were elicited at the time of the short (SLR)-,
      medium (MLR)- and long (LLR)-latency responses of the soleus muscle (SOL) during
      two-legged hopping on different stiffness surfaces, elastic and stiff. RESULTS:
      Soleus H-reflexes during two-legged hopping on the elastic surface were lower at
      SLR and larger at LLR than on the stiff surface (P < 0.05 for both comparisons).
      SOL MEP size was higher at the time of SLR during hopping on the elastic surface
      than on the stiff surface (P < 0.05) although the background EMG was similar.
      CONCLUSION: It is argued that this phase-specific adaptation in spinal reflex
      excitability is functionally relevant to adjust leg stiffness to optimally
      exploit the properties of the elastic surface. Thus, the increased corticospinal
      excitability on the elastic surface may reflect a more supraspinal control of the
      ankle muscles to compensate the decrease in reflexive stiffness at the beginning
      of touchdown and/or counteract the higher postural challenges associated with the
      elastic surface.

PMID- 25074474
TI  - The kinship2 R package for pedigree data.
AB  - BACKGROUND: The kinship2 package is restructured from the previous kinship
      package. Existing features are now enhanced and new features added for handling
      pedigree objects. METHODS: Pedigree plotting features have been updated to
      display features on complex pedigrees while adhering to pedigree plotting
      standards. Kinship matrices can now be calculated for the X chromosome. Other
      methods have been added to subset and trim pedigrees while maintaining the
      pedigree structure. CONCLUSION: We make the kinship2 package available for R on
      the Contributed R Archives Network (CRAN), where data management is built-in and
      other packages can use the pedigree object.

PMID- 25074476
TI  - The young ones and the old: past & future of science.

PMID- 25074475
TI  - Normal and abnormal development of the aortic wall and valve: correlation with
      clinical entities.
AB  - Dilation of the wall of the thoracic aorta can be found in patients with a
      tricuspid (TAV) as well as a bicuspid aortic valve (BAV) with and without a
      syndromic component. BAV is the most common congenital cardiovascular
      malformation, with a population prevalence of 0.5-2 %. The clinical course is
      often characterised by aneurysm formation and in some cases dissection. The non
      dilated aortic wall is less well differentiated in all BAV as compared with TAV,
      thereby conferring inherent developmental susceptibility. Furthermore, a
      turbulent flow, caused by the inappropriate opening of the bicuspid valve, could
      accelerate the degenerative process in the aortic wall. However, not all patients
      with bicuspidy develop clinical complications during their life. We postulate
      that the increased vulnerability for aortic complications in a subset of patients
      with BAV is caused by a defect in the early development of the aorta and aortic
      valve. This review discusses histological and molecular genetic aspects of the
      normal and abnormal development of the aortic wall and semilunar valves.
      Aortopathy associated with BAV could be the result of a shared developmental
      defect during embryogenesis. 

PMID- 25074477
TI  - State of the art of ICD programming: Lessons learned and future directions.
AB  - The lifesaving benefits of implantable cardioverter defibrillator (ICD) therapy
      are more and more weighted against possible harm (e.g. unnecessary device
      therapy, procedural complications, device malfunction etc.) which might have
      adverse effects on patients' perceived health status and quality of life. Hence,
      there has been an increasing interest in the optimisation of ICD programming to
      prevent inappropriate and appropriate but unnecessary device therapy. The purpose
      of the current report is to give an overview of research into the optimisation of
      ICD programming and present the design of the on-going ENHANCED-ICD study. The
      ENHANCED-ICD study is a prospective, safety monitoring study enrolling 60 primary
      and secondary prophylactic ICD patients at the University Medical Center Utrecht.
      Patients implanted with any type of ICD with SmartShock technology(TM), and
      between 18-80 years of age, were eligible to participate. In all patients a
      prolonged detection of 60/80 intervals was programmed. The primary objective of
      the study is to investigate whether enhanced programming to further reduce ICD
      therapies is safe. The secondary objective is to examine the impact of enhanced
      programming on (i) antitachycardia pacing and shocks (both appropriate and
      inappropriate) and (ii) quality of life and distress. The first results of the
      ENHANCED-ICD study are expected in 2015. 

PMID- 25074478
TI  - Comparison of biochemical failure rates between permanent prostate brachytherapy
      and radical retropubic prostatectomy as a function of posttherapy PSA nadir plus
      'X'.
AB  - BACKGROUND: Prostate-specific antigen (PSA) nadir + 2 ng/mL, also known as the
      Phoenix definition, is the definition most commonly used to establish biochemical
      failure (BF) after external beam radiotherapy for prostate cancer management. The
      purpose of this study is to compare BF rates between permanent prostate
      brachytherapy (PPB) and radical retropubic prostatectomy (RRP) as a function of
      PSA nadir plus varying values of X and examine the associated implications.
      METHODS AND MATERIALS: We retrospectively searched for patients who underwent PPB
      or RRP at our institution between 1998 and 2004. Only primary patients not
      receiving androgen-deprivation therapy were included in the study. Three RRP
      patients were matched to each PPB patient on the basis of prognostic factors. BF
      rates were estimated for PSA nadirs + different values of X. RESULTS: A total of
      1,164 patients were used for analysis: 873 in the RRP group and 291 in the PPB
      group. Patients were equally matched by clinical stage, biopsy Gleason sum,
      primary Gleason grade, and pretherapy PSA value. Median follow-up was 3.1 years
      for RRP patients and 3.6 years in the PPB group (P = .01). Using PSA nadir + 0.1
      ng/mL for the definition of BF, the 5-year BF rate was 16.3% for PPB patients and
      13.5% for RRP patients (P = .007), whereas at nadir + 2 ng/mL or greater, the BF
      rates were less than 3% and were indistinguishable between PPB and RRP patients.
      CONCLUSIONS: In a cohort of well-matched patients who had prostatectomy or
      brachytherapy, we examined BF as a function of nadir + X, where X was treated as
      a continuous variable. As X increases from 0.1 to 2.0 ng/mL, the BF curves
      converge, and above 2.0 ng/mL they are essentially indistinguishable. The data
      presented are of interest as BF definitions continue to evolve.

PMID- 25074479
TI  - Mesenchymal stem cell therapy in treatment of erectile dysfunction: autologous or
      allogeneic cell sources?
AB  - OBJECTIVE: To compare the efficacy of intracavernosal injection of autologous and
      allogeneic mesenchymal stem cells as potential treatment of erectile dysfunction
      in an experimental rat model. METHODS: Mesenchymal stem cells were isolated from
      rat paratesticular fat tissue. Bilateral cavernous nerve injury was carried out
      followed by immediate intracavernosal injection of either autologous or
      allogeneic mesenchymal stem cells or mesenchymal stem cell lysates. One month
      after injection, erectile function was evaluated by means of intracavernosal
      pressure measurement. All rats were eventually killed, and penile tissues were
      taken for immunhistochemical and molecular investigation. RESULTS: A total of 36
      Sprague-Dawley rats were used. The mean maximum intracavernosal pressure in the
      sham-operated, autologous and allogeneic mesenchymal stem cell injection groups
      were significantly better compared with the vehicle injection group (80.5 [3.56],
      71.1 [2.9] and 69.2 [3.2] vs 40.33 [4.4], respectively). Mean maximum
      intracavernosal pressure to mean arterial pressure ratios in the autologous and
      allogeneic mesenchymal stem cell and mesenchymal stem cell lysate injection
      groups were not significantly different. CONCLUSIONS: Intracavernosal injection
      of both autologous or allogeneic mesenchymal stem cells improve erectile
      functions in a rat model of cavernous nerve injury. Allogeneic mesenchymal stem
      cells might provide clinicians with ready to use, standardized and, in certain
      cases, more effective products. More studies focusing on long-term immunological
      aspects of allogeneic mesenchymal stem cells are required.

PMID- 25074481
TI  - Bayesian designs of phase II oncology trials to select maximum effective dose
      assuming monotonic dose-response relationship.
AB  - BACKGROUND: For many molecularly targeted agents, the probability of response may
      be assumed to either increase or increase and then plateau in the tested dose
      range. Therefore, identifying the maximum effective dose, defined as the lowest
      dose that achieves a pre-specified target response and beyond which improvement
      in the response is unlikely, becomes increasingly important. Recently, a class of
      Bayesian designs for single-arm phase II clinical trials based on hypothesis
      tests and nonlocal alternative prior densities has been proposed and shown to
      outperform common Bayesian designs based on posterior credible intervals and
      common frequentist designs. We extend this and related approaches to the design
      of phase II oncology trials, with the goal of identifying the maximum effective
      dose among a small number of pre-specified doses. METHODS: We propose two new
      Bayesian designs with continuous monitoring of response rates across doses to
      identify the maximum effective dose, assuming monotonicity of the response rate
      across doses. The first design is based on Bayesian hypothesis tests. To
      determine whether each dose level achieves a pre-specified target response rate
      and whether the response rates between doses are equal, multiple statistical
      hypotheses are defined using nonlocal alternative prior densities. The second
      design is based on Bayesian model averaging and also uses nonlocal alternative
      priors. We conduct simulation studies to evaluate the operating characteristics
      of the proposed designs, and compare them with three alternative designs.
      RESULTS: In terms of the likelihood of drawing a correct conclusion using similar
      between-design average sample sizes, the performance of our proposed design based
      on Bayesian hypothesis tests and nonlocal alternative priors is more robust than
      that of the other designs. Specifically, the proposed Bayesian hypothesis test
      based design has the largest probability of being the best design among all
      designs under comparison and the smallest probability of being an inadequate
      design, under sensible definitions of the best design and an inadequate design,
      respectively. CONCLUSIONS: The use of Bayesian hypothesis tests and nonlocal
      alternative priors under ordering constraints between dose groups results in a
      robust performance of the design, which is thus superior to other common designs.

PMID- 25074483
TI  - Asymmetric grazing incidence small angle x-ray scattering and anisotropic domain
      wall motion in obliquely grown nanocrystalline Co films.
AB  - Strong asymmetries have been observed in grazing incidence small angle x-ray
      scattering (GISAXS) in situ patterns obtained from 30 nm-thick nanocrystalline Co
      films prepared by oblique sputtering (15 degrees -75 degrees  off-sample normal).
      These asymmetries have been qualitatively simulated by a simple model consisting
      of an ensemble of 8 nm-wide inclined Co nanocolumns. It is found that narrow
      inclined features appear in the diffuse background resembling those
      characteristic of faceted systems, which can be used to obtain straightforward
      non-destructive estimations of buried nanocolumnar grains inclination, even for
      oblique angles below 45 degrees , when the stronger and broader asymmetric
      features of the pattern are not yet fully formed. Furthermore, using magneto
      optical microscopy, a marked change in the magnetic domain's nucleation and
      growth process has been observed in the sample prepared at 75 degrees , with the
      stronger GISAXS asymmetries. Easy axis magnetization reversal starts by a random
      and homogeneous nucleation of small (~MUm) elongated domains aligned with the
      nanocolumn's long axis and proceeds through the preferred propagation of head-to
      head domain walls (DWs) along the applied field direction. This peculiar magnetic
      behavior indicates that the strongly anisotropic nanostructuring created by the
      oblique growth process is equivalent, from a magnetic point of view, to an array
      of self-assembled buried nanowires. These results show how GISAXS and magneto
      optical microscopy can be combined as a powerful tool for correlating the
      morphology and magnetism of thin nanostructured systems. 

PMID- 25074480
TI  - STRengthening analytical thinking for observational studies: the STRATOS
      initiative.
AB  - The validity and practical utility of observational medical research depends
      critically on good study design, excellent data quality, appropriate statistical
      methods and accurate interpretation of results. Statistical methodology has seen
      substantial development in recent times. Unfortunately, many of these
      methodological developments are ignored in practice. Consequently, design and
      analysis of observational studies often exhibit serious weaknesses. The lack of
      guidance on vital practical issues discourages many applied researchers from
      using more sophisticated and possibly more appropriate methods when analyzing
      observational studies. Furthermore, many analyses are conducted by researchers
      with a relatively weak statistical background and limited experience in using
      statistical methodology and software. Consequently, even 'standard' analyses
      reported in the medical literature are often flawed, casting doubt on their
      results and conclusions. An efficient way to help researchers to keep up with
      recent methodological developments is to develop guidance documents that are
      spread to the research community at large. These observations led to the
      initiation of the strengthening analytical thinking for observational studies
      (STRATOS) initiative, a large collaboration of experts in many different areas of
      biostatistical research. The objective of STRATOS is to provide accessible and
      accurate guidance in the design and analysis of observational studies. The
      guidance is intended for applied statisticians and other data analysts with
      varying levels of statistical education, experience and interests. In this
      article, we introduce the STRATOS initiative and its main aims, present the need
      for guidance documents and outline the planned approach and progress so far. We
      encourage other biostatisticians to become involved.

PMID- 25074482
TI  - Health Equilibrium Initiative: a public health intervention to narrow the health
      gap and promote a healthy weight in Swedish children.
AB  - BACKGROUND: Inequity in health is a global concern. Even in Sweden there are
      considerable health gaps between different social groups, not least concerning
      life-style related conditions. Interventions drawing on Community-based
      participatory research (CBPR) have potential to build prerequisites for complex,
      supportive structures that constitute basis for implementation of sustainable
      health promoting programs. CBPR rests on principles of empowerment. The
      researchers are responsible for the scientific quality and that ethical standards
      are met. Health Equilibrium Initiative (HEI) aims at narrowing the health gap and
      promoting healthy weight in children; "healthy weight" including both
      anthropometric criteria and aspects having to do with self-esteem and self
      efficacy. Evaluation objectives are to compare outcome between children in
      intervention and control areas, conduct health economic assessments (HEA) and
      evaluate the processes of the project. METHODS/DESIGN: HEI is a repeated cross
      sectional and longitudinal study. The Program Logic Model is based on Social
      Cognitive Theory and Intervention Mapping. Primary contact groups are children in
      disadvantaged communities. Core efforts are to confirm and convey knowledge,
      elucidate and facilitate on-going health work and support implementation of
      continuous health work. Socioeconomic status is assessed on area level by the
      parameters yearly average income, degree of employment, tertiary education and
      percent of inhabitants born in countries where violent conflicts recently have
      taken place or were ongoing. Anthropometry, food patterns, physical activity and
      belief in ability to affect health; together with learning, memory and attention
      assessment will be assessed in 350 children (born 2006). Examinations will be
      repeated after two years, forming the basis of a health economic analysis. The
      process evaluation procedure will use document analysis (such as structured
      reports from meetings and dialogues, school/workplaces policies and curriculum,
      food service menus); key informant interviews and focus groups with parents,
      children and professionals. DISCUSSION: Inviting, awaiting and including local
      perspectives create mutual confidence and collaboration. Enhanced self-efficacy
      and access to relevant knowledge has potential to enable individuals and
      communities to choose alternatives that are relevant for their health and well
      being in a long perspective. The economic of this study may contribute in
      decision- making processes regarding appropriate public health interventions.

PMID- 25074484
TI  - Perception of pediatric pain: a comparison of postoperative pain assessments
      between child, parent, nurse, and independent observer.
AB  - INTRODUCTION: Pain is a subjective experience. In children with limited
      understanding and communication skills, reliable assessment of pain is
      challenging. Self-reporting of pain is the gold standard of pain measurement. For
      children who are unable to self-report their pain, assessments made by their
      parents are often used as a proxy measure. The validity of this approach has not
      been conclusively determined. AIM: To investigate differences in the assessment
      of pediatric pain between children, parents, nurses, and independent observers in
      the acute postoperative setting. METHOD: Three hundred and seven children (207
      verbal, 100 nonverbal) undergoing elective day-case surgery were asked to
      participate in this quality of care audit. Pain scores given by verbal children,
      their parents, nurses, and independent observers were collected. A numerical
      rating scale or the Wong-Baker Faces Pain Scale was used. All participants were
      blinded from other scorers. RESULTS: For verbal children, scores reported by
      patients and their parents did not differ significantly. Median [inter-quartile
      range (IQR)] scores by children, parents, nurses, and independent observers were,
      respectively, 2.0 (0-4.0), 2.0 (1.0-4.0), 0.0 (0-2.0), and 1.0 (0-2.0). In
      nonverbal children, median (IQR) scores by parents, nurses, and independent
      observers were 1.0 (0-3.0), 0 (0-1.0), and 0 (0-2.0), respectively. The agreement
      between the different scorers was statistically significant. CONCLUSION:
      Children's pain self-reports should be used wherever possible to guide
      management, but in their absence, parental pain scores can be reliably used as a
      surrogate measure. Nurses and independent observers produce lower pain scores
      than parents or children, which may result in inadequate treatment of pain.

PMID- 25074485
TI  - Effect of long-term supplementation of low molecular weight chitosan
      oligosaccharide (GO2KA1) on fasting blood glucose and HbA1c in db/db mice model
      and elucidation of mechanism of action.
AB  - BACKGROUND: Type 2 diabetes is a serious problem for developed countries.
      Prevention of prediabetes progression to type 2 diabetes with the use of natural
      products appears to a cost-effective solution. Previously we showed that
      enzymatically digested low molecular weight chitosan-oligosaccharide with
      molecular weight (MW) below 1,000 Da (GO2KA1) has potential for hyperglycemia
      management. METHODS: In this study we evaluated the effect of long-term
      supplementation of GO2KA1 on hyperglycemia using a db/db mice model.
      Additionally, we evaluated the effect of GO2KA1 on sucrase and glucoamylase
      activities and expression, using the same db/db mice model. RESULTS: After 42
      days we observed that GO2KA1 supplementation reduced both the blood glucose level
      and HbA1c in a similar manner with a known anti-diabetic drug, acarbose. When the
      sucrase and glucoamylase activities of GO2KA1 and control mice were evaluated
      using enzymatic assay, we observed that GO2KA1 significantly inhibited sucrase in
      all 3 parts of the intestine, while glucoamylase activity was significantly
      reduced only in the middle and lower part. When the sucrase-isomaltase (SI)
      complex expression on mRNA level was evaluated, we observed that GO2KA1 had
      minimal inhibitory effect on the upper part, more pronounced inhibitory effect on
      the middle part, while the highest inhibition was observed on the lower part. Our
      findings suggest that long-term GO2KA1 supplementation in db/db mice results to
      significant blood glucose and HbA1c reduction, to levels similar with those of
      acarbose. Furthermore, our findings confirm previous in vitro observations that
      GO2KA1 has inhibitory effect on carbohydrate hydrolysis enzymes, namely sucrase,
      maltase and SI complex. CONCLUSIONS: Results from this study provide a strong
      rationale for the use of GO2KA1 for type 2 diabetes prevention, via inhibition of
      carbohydrate hydrolysis enzymes. Based on the findings of this animal trial,
      clinical trials will be designed and pursued.

PMID- 25074486
TI  - Bisphenol A regulates the estrogen receptor alpha signaling in developing
      hippocampus of male rats through estrogen receptor.
AB  - Bisphenol A (BPA), one of the most common environmental endocrine disruptors, has
      been recognized to have wide adverse effects on the brain development and
      behavior. These adversities are related to its ability to bind estrogen receptor
      (ER) with subsequent alteration of its expression in the target areas. However,
      very little is known about whether BPA exposure also affects ER phosphorylation
      and its translocation to nucleus during postnatal development, two critical steps
      for its function. Here, we found that during development from postnatal day 7
      (P7) to P21, the alpha subtype of ER (ERalpha) in the hippocampus of male rats
      experienced remarkable alterations in terms of its expression, phosphorylation
      and translocation to nucleus. Exposure to low level of BPA had bidirectional,
      development-dependent effects on the expression of ERalpha mRNA and protein, but
      decreased ERalpha phosphorylation and impaired its translocation to nucleus
      throughout the period investigated. Treatment with low dose of ICI 182,780 (ICI),
      an ER antagonist to block the binding of ER with BPA, reversed the altered
      ERalpha following BPA exposure, highlighting critical involvement of ER.
      Moreover, ICI treatment rescued the hippocampus-dependent behavioral deficits in
      the adult rats experiencing early-life BPA exposure. Overall, our results
      indicate that BPA interferes with the ERalpha signaling in the developing
      hippocampus in an ER-dependent manner, which may underlie its adverse behavioral
      and cognitive outcomes in adult animals.

PMID- 25074487
TI  - Transmembrane channel-like (TMC) genes are required for auditory and vestibular
      mechanosensation.
AB  - Mutations of the transmembrane channel-like 1 (TMC1) gene can cause dominant and
      recessive forms of deafness in humans and mice. TMC1 is one of eight mammalian
      TMC genes of unknown function. The multi-pass transmembrane topologic structure
      of the proteins they encode suggests roles as a receptor, transporter, channel,
      or pump. Tmc1 and the closely related Tmc2 gene are expressed in neurosensory
      hair cells of the auditory and vestibular end organs of the mouse inner ear.
      Recent studies have demonstrated that Tmc1 and Tmc2 are specifically required for
      mechanoelectrical transduction in hair cells. The exact role of these proteins in
      mechanoelectrical transduction is unknown. TMC1 and TMC2 are viable candidates
      for the mechanoelectrical transduction channel of hair cells, whose component
      molecules have eluded identification for over 30 years. We expect that studies of
      TMC proteins will yield insights into molecular components and mechanisms of
      mechanosensation in auditory and vestibular hair cells, as well as in other
      tissues and organs.

PMID- 25074488
TI  - Glucose deprivation promotes activation of mTOR signaling pathway and protein
      synthesis in rat skeletal muscle cells.
AB  - Signaling through mammalian target of rapamycin (mTOR) has been shown to play a
      central role in the regulation of skeletal muscle growth induced by a wide range
      of stimuli either mechanical or metabolic, such as growth factors and amino
      acids. Here, we demonstrate that mTOR and its downstream target, the ribosomal S6
      kinase (p70(S6K)), are activated in L6 myocytes by a short-term glucose
      deprivation. Such response is specific of skeletal muscle and is likely
      responsible for the increased rate of protein synthesis and expression of the
      muscle-specific proteins during recovery from glucose deprivation. Nitric oxide
      and phosphatidylinositol-3-kinase (PI3K) are upstream positive regulators of mTOR
      since their pharmacological inhibition prevents the activation of p70(S6K) in
      response to glucose deprivation. We therefore propose a model of response to a
      brief period of glucose deprivation that may occur in skeletal muscle cells
      during resistance exercise and that may lead to protein accretion when blood flow
      recovers and all nutrients are again available. 

PMID- 25074490
TI  - A child with a novel de novo mutation in the aristaless domain of the aristaless
      related homeobox (ARX) gene presenting with ambiguous genitalia and psychomotor
      delay.
AB  - The objective of this study was to identify disease-causing mutations in a Sri
      Lankan male child presenting with ambiguous genitalia and psychomotor delay using
      the exome sequencing approach. A novel mutation in the aristaless-related
      homeobox (ARX) gene causing a hemizygous nucleotide substitution in exon 5 was
      identified (NM_139058.2 (ARX): c.1614G>T; p.K538N). This change causes a
      nonsynonymous substitution in the aristaless domain within the ARX protein which
      is predicted to be deleterious. This is the first reported case of ambiguous
      genitalia and psychomotor delay associated with this novel missense mutation
      within the ARX protein, and it highlights the value of exome sequencing even in
      sporadic cases.

PMID- 25074491
TI  - Insulin resistance, diabetes mellitus, and brain structure in bipolar disorders.
AB  - Type 2 diabetes mellitus (T2DM) damages the brain, especially the hippocampus,
      and frequently co-occurs with bipolar disorders (BD). Reduced hippocampal volumes
      are found only in some studies of BD subjects and may thus be secondary to the
      presence of certain clinical variables. Studying BD patients with abnormal
      glucose metabolism could help identify preventable risk factors for hippocampal
      atrophy in BD. We compared brain structure using optimized voxel-based
      morphometry of 1.5T MRI scans in 33 BD subjects with impaired glucose metabolism
      (19 with insulin resistance/glucose intolerance (IR/GI), 14 with T2DM), 15
      euglycemic BD participants and 11 euglycemic, nonpsychiatric controls. The group
      of BD patients with IR, GI or T2DM had significantly smaller hippocampal volumes
      than the euglycemic BD participants (corrected p=0.02) or euglycemic,
      nonpsychiatric controls (corrected p=0.004). Already the BD subjects with IR/GI
      had smaller hippocampal volumes than euglycemic BD participants (t(32)=-3.15,
      p=0.004). Age was significantly more negatively associated with hippocampal
      volumes in BD subjects with IR/GI/T2DM than in the euglycemic BD participants
      (F(2, 44)=9.96, p=0.0003). The gray matter reductions in dysglycemic subjects
      extended to the cerebral cortex, including the insula. In conclusion, this is the
      first study demonstrating that T2DM or even prediabetes may be risk factors for
      smaller hippocampal and cortical volumes in BD. Abnormal glucose metabolism may
      accelerate the age-related decline in hippocampal volumes in BD. These findings
      raise the possibility that improving diabetes care among BD subjects and
      intervening already at the level of prediabetes could slow brain aging in BD. 

PMID- 25074489
TI  - Potassium channels in pancreatic duct epithelial cells: their role, function and
      pathophysiological relevance.
AB  - Pancreatic ductal epithelial cells play a fundamental role in HCO3 (-) secretion,
      a process which is essential for maintaining the integrity of the pancreas.
      Although several studies have implicated impaired HCO3 (-) and fluid secretion as
      a triggering factor in the development of pancreatitis, the mechanism and
      regulation of HCO3 (-) secretion is still not completely understood. To date,
      most studies on the ion transporters that orchestrate ductal HCO3 (-) secretion
      have focussed on the role of Cl(-)/HCO3 (-) exchangers and Cl(-) channels,
      whereas much less is known about the role of K(+) channels. However, there is
      growing evidence that many types of K(+) channels are present in ductal cells
      where they have an essential role in establishing and maintaining the
      electrochemical driving force for anion secretion. For this reason, strategies
      that increase K(+) channel function may help to restore impaired HCO3 (-) and
      fluid secretion, such as in pancreatitis, and therefore provide novel directions
      for future pancreatic therapy. In this review, our aims are to summarize the
      types of K(+) channels found in pancreatic ductal cells and to discuss their
      individual roles in ductal HCO3 (-) secretion. We will also describe how K(+)
      channels are involved in pathophysiological conditions and discuss how they could
      act as new molecular targets for the development of therapeutic approaches to
      treat pancreatic diseases. 

PMID- 25074492
TI  - Newly identified pathogens associated with periodontitis: a systematic review.
AB  - There is substantial evidence supporting the role of certain oral bacteria
      species in the onset and progression of periodontitis. Nevertheless, results of
      independent-culture diagnostic methods introduced about a decade ago have pointed
      to the existence of new periodontal pathogens. However, the data of these studies
      have not been evaluated together, which may generate some misunderstanding on the
      actual role of these microorganisms in the etiology of periodontitis. The aim of
      this systematic review was to determine the current weight of evidence for newly
      identified periodontal pathogens based on the results of "association" studies.
      This review was conducted and reported in accordance with the PRISMA statement.
      The MEDLINE, EMBASE, and Cochrane databases were searched up to September 2013
      for studies (1) comparing microbial data of subgingival plaque samples collected
      from subjects with periodontitis and periodontal health and (2) evaluating at
      least 1 microorganism other than the already-known periodontal pathogens. From
      1,450 papers identified, 41 studies were eligible. The data were extracted and
      registered in predefined piloted forms. The results suggested that there is
      moderate evidence in the literature to support the association of 17 species or
      phylotypes from the phyla Bacteroidetes, Candidatus Saccharibacteria, Firmicutes,
      Proteobacteria, Spirochaetes, and Synergistetes. The phylum Candidatus
      Saccharibacteria and the Archaea domain also seem to have an association with
      disease. These data point out the importance of previously unidentified species
      in the etiology of periodontitis and might guide future investigations on the
      actual role of these suspected new pathogens in the onset and progression of this
      infection. 

PMID- 25074493
TI  - Periodontal microbiology--the lid's off the box again.

PMID- 25074494
TI  - Zoledronate and ion-releasing resins impair dentin collagen degradation.
AB  - This study analyzed the amounts of solubilized telopeptides cross-linked
      carboxyterminal telopeptide of type I collagen (ICTP) and C-terminal crosslinked
      telopeptide of type I collagen (CTX) derived from matrix-metalloproteinases
      (MMPs) and cysteine cathepsins (CTPs) subsequent to application of a filler-free
      (Res.A) or an ion-releasing resin (Res.B) to ethylenediaminetetraacetic acid
      (EDTA)-demineralized dentin with or without zoledronate-containing primer (Zol
      primer) pre-treatment. The chemical modification induced following treatments and
      artificial saliva (AS) storage was also analyzed through attenuated total
      reflection Fourier transform infrared spectroscopy (ATR-FTIR). Totally EDTA
      demineralized specimens were infiltrated with Res.A or Res.B with or without Zol
      primer pre-treatment, light-cured, and immersed in AS for up to 4 wk. ICTP
      release was reduced following infiltration with Res.B and further reduced when
      Res.B was used with Zol-primer; remarkable phosphate mineral uptake was attained
      after AS storage. CTX release was increased in Res.A- and Res.B-treated dentin.
      However, when Zol-primer was used with Res.A, the CTX release fell significantly
      compared to the other tested resin-infiltration methods. In conclusion,
      zoledronate offers an additional inhibitory effect to the ion-releasing resins in
      MMP-mediated collagen degradation. However, Zol-primer induces a modest reduction
      in CTX release only when used with resin-based systems containing no ion
      releasing fillers. 

PMID- 25074495
TI  - Fluoride affects enamel protein content via TGF-beta1-mediated KLK4 inhibition.
AB  - Dental fluorosis is caused by chronic high-level fluoride (F(-)) exposure during
      enamel development, and fluorosed enamel has a higher than normal protein
      content. Matrix metalloproteinase 20 cleaves enamel matrix proteins during the
      secretory stage, and KLK4 further cleaves these proteins during the maturation
      stage so that the proteins can be reabsorbed from the hardening enamel. We show
      that transforming growth factor beta1 (TGF-beta1) can induce Klk4 expression, and
      we examine the effect of F(-) on TGF-beta1 and KLK4 expression. We found that in
      vivo F(-) inhibits Klk4 but not Mmp20 transcript levels. LacZ-C57BL/6-Klk4
      (+/LacZ) mice have LacZ inserted in frame at the Klk4 translation initiation site
      so that the endogenous Klk4 promoter drives LacZ expression in the same
      temporal/spatial way as it does for Klk4. KLK4 protein levels in rat enamel and
      beta-galactosidase staining in LacZ-C57BL/6-Klk4 (+/LacZ) mouse enamel were both
      significantly reduced by F(-) treatment. Since TGF-beta1 induces KLK4 expression,
      we tested and found that F(-) significantly reduced Tgf-beta1 transcript levels
      in rat enamel organ. These data suggest that F(-)-mediated downregulation of TGF
      beta1 expression contributes to reduced KLK4 protein levels in fluorosed enamel
      and provides an explanation for why fluorosed enamel has a higher than normal
      protein content. 

PMID- 25074496
TI  - Downregulation of Centaurin gamma1A increases synaptic transmission at Drosophila
      larval neuromuscular junctions.
AB  - Adequate regulation of synaptic transmission is critical for appropriate neural
      circuit functioning. Although a number of molecules involved in synaptic
      neurotransmission have been identified, the molecular mechanisms regulating
      neurotransmission are not fully understood. Here, we focused on Centaurin gamma1A
      (CenG1A) and examined its role in synaptic transmission regulation using
      Drosophila larval neuromuscular junctions. CenG1A is a member of the Centaurin
      family, which contains Pleckstrin homology, ADP ribosylation factor GTPase
      activating protein, and ankyrin repeat domains. Due to the existence of these
      functional domains, CenG1A is proposed to be involved in the process of synaptic
      release; however, no evidence for this has been found to date. In this study, we
      investigated the potential role for CenG1A in the process of synaptic release by
      performing intracellular recordings in larval muscle cells. We found that
      neurotransmitter release from presynaptic cells was enhanced in cenG1A mutants.
      This effect was also observed in larvae with reduced CenG1A function in either
      presynaptic or postsynaptic cells. In addition, we revealed that suppressing
      CenG1A function in postsynaptic muscle cells led to an increase in the
      probability of neurotransmitter release, whereas its suppression in presynaptic
      neurons led to an increase in neurotransmitter release probability and an
      increase in the number of synaptic vesicles. These results suggested that CenG1A
      functions at both presynaptic and postsynaptic sites as a negative regulator of
      neurotransmitter release. Our study provided evidence for a key role of CenG1A in
      proper synaptic transmission at neuromuscular junctions. 

PMID- 25074497
TI  - Evans syndrome after unrelated bone marrow transplantation for refractory
      cytopenia of childhood.
AB  - Post-transplant ES, which is often resistant to therapies, has seldom been
      described. This report describes a case of ES after UBMT for RCC. A five-yr-old
      boy developed RCC with no evidence of monosomy 7. Because no matching family
      donors were available for SCT and immunosuppressive therapy was ineffective, UBMT
      was performed when he was six yr old. The conditioning regimen included TAI (3
      Gy) and administration of FLU, CY, and rabbit antithymocyte globulin. The
      recovery of blood cells was good. He displayed grade II acute GVHD involving only
      the skin. ES developed on day 66, with positive results for Epstein-Barr virus
      DNA and HHV 6. Cytopenia was resolved with treatment with RTX, GCV, an escalated
      dose of steroids, high-dose gammaglobulin, and romiplostim. No relapse has
      occurred since discontinuing steroids on day 177 and romiplostim on day 268. Post
      SCT ES after UBMT is rare, and the risk factors and therapies are unclear.
      Prospective analysis and collection of cases from multiple centers are required
      for clarification. 

PMID- 25074498
TI  - Boveri at 100: Theodor Boveri and genetic predisposition to cancer.
AB  - One hundred years have passed since the publication of Theodore Boveri's Zur
      Frage der Entstehung maligner Tumouren [Concerning the Origin of Malignant
      Tumours]. This prescient publication created the foundations for much of our
      understanding of the origins of cancer and in particular the genetic basis of
      some cancers. In his work, Boveri suggested that loss of key cellular attributes,
      now known as tumour suppressor genes, are a key driver event in the development
      of cancer and inheritance could play a role in cancer susceptibility. He also
      predicted that chromosomal (genomic) instability as a key hallmark of cancer.
      Whilst these key insights that still inform the practice of cancer genetics, they
      were not the main theme of Boveri's text, which was to describe the role of
      chromosomal abnormalities in the development of cancer. In making his case he
      also suggested that genetic information could be contained in distinct packages
      (genes) that are linearly arranged along chromosomes and that cancers arise from
      single cells. These remarkably accurate hypotheses add weight to the need to
      celebrate this landmark publication for its accurate prediction of so much that
      we take for granted. Here we focus on Boveri's contributions to our understanding
      of hereditary cancers, which, alongside the astute clinical observations of Paul
      Broca and Aldred Scott Warthin, were published decades before the field became
      respectable, yet could still inform anyone studying hereditary cancers.

PMID- 25074500
TI  - Polymorphisms of beta2-adrenergic receptor gene in serbian asthmatic adults:
      effects on response to Beta-agonists.
AB  - BACKGROUND AND OBJECTIVES: Polymorphisms of beta2-adrenergic receptor gene
      (ADRB2) are clinically relevant for several reasons, including as a risk factor
      for asthma development/severity and predicting the effectiveness of treatment
      with beta2-agonists in reducing asthma symptoms. The aim of this study was to
      examine the association between ADRB2 gene polymorphisms and asthma in the
      Serbian population, and to evaluate the therapeutic response in relation to the
      ADRB2 genotype. METHODS: The study included 171 patients with asthma and 101
      healthy subjects as the control group. Genotyping of Arg16Gly and Gln27Glu
      polymorphisms was performed by direct sequencing of polymerase chain reaction
      (PCR) products. RESULTS: In Serbian adults, carriers of the 27Gln allele and
      27Gln/Gln genotype were at higher risk of asthma [odds ratio (OR) 2.5, 95%
      confidence interval (CI) 1.6-3.8, and OR 3.00, 95% CI 1.7-5.3, respectively],
      while the presence of the 27Glu allele and 27Gln/Glu genotype were found to be
      protective of asthma (OR 0.4, 95% CI 0.3-0.6, and OR 0.3, 95% CI 0.1-0.7,
      respectively). Furthermore, we found that the presence of the 27Gln allele in
      asthmatics younger than 50 years leads to a better response to therapy with long
      acting beta2-agonists (LABA) in combination with prevailing low and moderate
      doses of inhaled corticosteroids (ICS), while carriers of the 27Glu allele over
      50 years old are more likely to respond to LABA + ICS therapy. CONCLUSION: We
      identified that in Serbian adults the 27Gln allele and 27Gln homozygosity are
      risk factors for asthma, which may be of clinical interest in disease prevention.
      The finding that younger carriers of the 27Gln allele respond better to LABA +
      ICS therapy may be utilized in personalized asthma treatment.

PMID- 25074501
TI  - Social closeness and feedback modulate susceptibility to the framing effect.
AB  - Although we often seek social feedback (SFB) from others to help us make
      decisions, little is known about how SFB affects decisions under risk,
      particularly from a close peer. We conducted two experiments using an established
      framing task to probe how decision-making is modulated by SFB valence (positive,
      negative) and the level of closeness with feedback provider (friend,
      confederate). Participants faced mathematically equivalent decisions framed as
      either an opportunity to keep (gain frame) or lose (loss frame) part of an
      initial endowment. Periodically, participants were provided with positive (e.g.,
      "Nice!") or negative (e.g., "Lame!") feedback about their choices. Such feedback
      was provided by either a confederate (Experiment 1) or a gender-matched close
      friend (Experiment 2). As expected, the framing effect was observed in both
      experiments. Critically, an individual's susceptibility to the framing effect was
      modulated by the valence of the SFB, but only when the feedback provider was a
      close friend. This effect was reflected in the activation patterns of
      ventromedial prefrontal cortex and posterior cingulate cortex, regions involved
      in complex decision-making. Taken together, these results highlight social
      closeness as an important factor in understanding the impact of SFB on neural
      mechanisms of decision-making.

PMID- 25074502
TI  - Development and characterization of GRGDSPC-modified poly(lactide-co-glycolide
      acid) porous microspheres incorporated with protein-loaded chitosan microspheres
      for bone tissue engineering.
AB  - Scaffolds that can achieve cell adhesion and controlled release of protein drugs
      are very promising in bone tissue engineering. Due to their biocompatibility and
      injectablity, poly(lactide-co-glycolide acid) (PLGA) porous microspheres (PLGA
      pMS) present potential scaffolds in bone tissue engineering. However, their
      application is hampered by the burst release of protein drugs and hydrophobicity
      that leads to poor cell adhesion. To overcome these drawbacks, we developed novel
      PLGA-pMS by incorporating bovine serum albumin (BSA) loaded chitosan microspheres
      (CS-MS) in Gly-Arg-Gly-Asp-Ser-Pro-Cys (GRGDSPC) modified PLGA-pMS (CS-MS/PLGA
      pMS). GRGDSPC was used to enhance the hydrophilicity and cell affinity of the
      porous microspheres. Results showed that PLGA-pMS had a size of 446.77+/
      19.46MUm, with an average surface pore size of 21.56+/-3.02MUm, whereas CS-MS had
      a size of 15.98+/-0.96MUm and 16.35+/-0.38MUm (5% and 10% TPP-prepared CS-MS,
      respectively). A scanning electron microscope (SEM) and a confocal laser scanning
      microscope (CLSM) revealed that CS-MS were partly embedded in the PLGA matrices
      and the integrity of CS-MS was retained. Thermogravimetry analyzer (TGA) also
      demonstrated that CS-MS were incorporated into PLGA-pMS. The CS-MS/PLGA-pMS had a
      size of 454.02+/-16.09MUm, with a BSA encapsulation efficiency of 53.19+/-1.67%
      and 62.16+/-3.44% (5% and 10% TPP-prepared CS-MS, respectively). CS-MS/PLGA-pMS
      exhibited a sustained FITC-BSA release for 28 days. Modification of GRGDSPC
      significantly improved adhesion of MG-63 cells on the porous microspheres. In
      conclusion, CS-MS/PLGA-pMS may act as potential bifunctional scaffolds for bone
      tissue engineering. 

PMID- 25074503
TI  - Understanding the fouling of algogenic organic matter in microfiltration using
      membrane-foulant interaction energy analysis: effects of organic hydrophobicity.
AB  - Fouling caused by algogenic organic matter (AOM) in membrane filtration is a
      critical problem in algae-rich waters, and understanding fouling mechanisms,
      particularly by identifying the predominant membrane foulants, could have
      significant effects on algal fouling prediction and pretreatment. In this work,
      the fouling behavior of Aphanizomenon flos-aquae (APF)- and Anabaena flos-aquae
      (ANF)-AOM fractions was analyzed using the extended Derjaguin-Landau-Verwey
      Overbeek (XDLVO) theory. The results show that the interfacial energy of
      membranes and foulants could be used for AOM membrane fouling analysis. The
      attractive energy was highest between the membrane and the neutral hydrophilic
      fractions (N-HPI) on clean membrane surfaces, followed by the energy associated
      with the hydrophobic fractions (HPO) and the transphilic fractions (TPI) in both
      of the AOMs; on the other hand, the negatively charged hydrophilic organics (C
      HPI) in the APF-AOM suffered from repulsive interactions when nearing the
      membrane surface, which was consistent with their initial filtration flux. After
      the formation of an initial fouling layer on the membrane surface, membrane
      fouling was controlled mainly by the cohesion free energy between the approaching
      foulants and the foulants on the fouled membranes. In addition, it was observed
      that the interfacial energy between foulants was the dominant factor controlling
      membrane fouling in AOM filtration. Finally, the interfacial energies between the
      N-HPI fractions had the greatest effect on both APF-AOM and ANF-AOM membrane
      fouling. 

PMID- 25074505
TI  - Evolution of left ventricular ejection fraction after acute myocardial
      infarction: implications for implantable cardioverter-defibrillator eligibility.
AB  - BACKGROUND: Implantable cardioverter-defibrillator therapy improves survival in
      patients with reduced left ventricular ejection fraction (LVEF) after acute
      myocardial infarction (AMI). Although the risk of sudden cardiac death is highest
      in the first month after AMI, there is no survival benefit of early implantable
      cardioverter-defibrillator implantation, and the optimal time frame has yet to be
      established. Thus, the aim of this study was to investigate what proportion of
      post-AMI patients had improved LV function to such an extent that the indication
      for implantable cardioverter-defibrillator was no longer present. METHODS AND
      RESULTS: Patients admitted for AMI with reduced LVEF (<=40%) were eligible for
      inclusion. Repeat echocardiographic examinations were performed 5 days, 1 month,
      and 3 months after the AMI. We prospectively included 100 patients with LVEF of
      31+/-5.8% after AMI. At the 1-month follow-up, 55% had an LVEF >35%. The main
      improvement in LVEF had occurred by 1 month. The mean difference in LVEF over the
      next 2 months was small, 1.9 percentage units. During the first 9 weeks, 10% of
      the patients suffered from life-threatening arrhythmias. CONCLUSIONS: Most
      patients have improved LVEF after AMI, and in the majority, the improvement can
      be confirmed after 1 month, implying that further delay of implantable
      cardioverter-defibrillator implantation may not be warranted. Life-threatening
      arrhythmias occurred in 10% of the patients, illustrating the high risk for
      sudden cardiac death in this population.

PMID- 25074506
TI  - Survival of the fittest: evolution of left ventricular ejection fraction after
      acute myocardial infarction.

PMID- 25074504
TI  - Response shift in quality of life after endoscopic sinus surgery for chronic
      rhinosinusitis.
AB  - IMPORTANCE: Patient-reported measures are designed to detect a true change in
      outcome, but they are also subject to change from biases inherent to self
      reporting: changing internal standards, changing priorities, and changing
      interpretations of a given instrument. These biases are collectively known as
      "response shifts" and can obscure true change after medical interventions.
      OBJECTIVE: To determine the presence of response shifts in patients with chronic
      rhinosinusitis (CRS) after endoscopic sinus surgery. DESIGN, SETTING, AND
      PARTICIPANTS: Multisite, prospective, observational cohort study conducted at
      academic tertiary care centers between February 2011 and May 2013. Study
      participants comprised a population-based sample of 514 adults (age >=18 years)
      with CRS, who elected surgical intervention for continuing medically refractory
      symptoms. INTERVENTION: Endoscopic sinus surgery. MAIN OUTCOMES AND MEASURES:
      Preoperative and postoperative data from the 22-item Sinonasal Outcome Test (SNOT
      22) survey instrument was characterized using exploratory factor analysis.
      Subsequent longitudinal structural equation models were estimated to test
      structure, potential response shifts, and true change in the SNOT-22 scores.
      RESULTS: A total of 339 participants (66.0%) provided survey evaluations at
      baseline and 6-month follow-up. Factor analysis of the SNOT-22 revealed 5
      correlated, yet distinguishable, underlying factors. Endoscopic sinus surgery had
      a differential impact across these factors, with the largest effect size in
      rhinologic symptoms (mean [SD] SNOT-22 scores before and after surgery, 13.18
      [5.11] and 7.37 [5.48], respectively; d = -1.13 [P < .001]) and extranasal
      rhinologic symptoms (8.31 [3.46] and 4.83 [3.68], respectively; d = -1.00 [P <
      .05]) (d is an effect size measure defined as the difference in means divided by
      the presurgery SD). Endoscopic sinus surgery had a smaller, yet significant,
      effect size on the remaining 3 factors: ear/facial symptoms (7.32 [4.6]) and 3.90
      [4.07], respectively; d = -0.74 [P < .001]), psychological dysfunction (11.90
      [7.21] and 6.50 [6.69], respectively; d = -0.75 [P < .05]), and sleep dysfunction
      (10.12 [5.59] and 5.88 [5.37], respectively; d = -0.76 [P < .001]). Participants
      were found to undergo recalibration, reprioritization, and reconceptualization of
      symptoms after intervention; however, the magnitude of these response shifts was
      small and not clinically significant. CONCLUSIONS AND RELEVANCE: The SNOT-22
      measures 5 distinct factors, not a single construct. Reporting of individual
      subscale scores may improve sensitivity of this instrument in future studies.
      Participants undergoing endoscopic sinus surgery experience only clinically
      insignificant response shifts, validating assessment of change through use of
      presurgery and postsurgery SNOT-22 responses. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01332136.

PMID- 25074507
TI  - Nesiritide, renal function, and associated outcomes during hospitalization for
      acute decompensated heart failure: results from the Acute Study of Clinical
      Effectiveness of Nesiritide and Decompensated Heart Failure (ASCEND-HF).
AB  - BACKGROUND: Contradictory results have been reported on the effects of nesiritide
      on renal function in patients with acute decompensated heart failure. We studied
      the effects of nesiritide on renal function during hospitalization for acute
      decompensated heart failure and associated outcomes. METHODS AND RESULTS: A total
      of 7141 patients were randomized to receive either nesiritide or placebo and
      creatinine was recorded in 5702 patients at baseline, after infusion, discharge,
      peak/nadir levels until day 30. Worsening renal function was defined as an
      increase of serum creatinine >0.3 mg/dL and a change of >=25%. Median (25(th)
      75(th) percentile) baseline creatinine was 1.2 (1.0-1.6) mg/dL and median
      baseline blood urea nitrogen was 25 (18-39) mmol/L. Changes in both serum
      creatinine and blood urea nitrogen were similar in nesiritide-treated and placebo
      treated patients (P=0.20 and P=0.41) from baseline to discharge. In a
      multivariable model, independent predictors of change from randomization to
      hospital discharge in serum creatinine were a lower baseline blood urea nitrogen,
      higher systolic blood pressure, lower diastolic blood pressure, previous weight
      gain, and lower baseline potassium (all P<0.0001). The frequency of worsening
      renal function during hospitalization was similar in the nesiritide and placebo
      group (14.1% and 12.8%, respectively; odds ratio with nesiritide 1.12; confidence
      interval, 0.95-1.32; P=0.19) and was not associated with death alone and death or
      rehospitalization at 30 days. However, baseline, discharge, and change in
      creatinine were associated with death alone and death or rehospitalization for
      heart failure (all tests, P<0.0001). CONCLUSIONS: Nesiritide did not affect renal
      function in patients with acute decompensated heart failure. Baseline, discharge,
      and change in renal function were associated with 30-day mortality or
      rehospitalization for heart failure.

PMID- 25074508
TI  - Renal subanalysis of the Acute Study of Clinical Effectiveness of Nesiritide in
      Decompensated Heart Failure (ASCEND-HF): the end of nesiritide as a cardiorenal
      therapeutic?

PMID- 25074509
TI  - Imaging-based diagnosis of autosomal dominant polycystic kidney disease.
AB  - The clinical use of conventional ultrasonography (US) in autosomal dominant
      polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic
      sensitivity, especially in at-risk subjects younger than 30 years of age. In this
      single-center prospective study, we compared the diagnostic performance of MRI
      with that of high-resolution (HR) US in 126 subjects ages 16-40 years born with a
      50% risk of ADPKD who underwent both these renal imaging studies and
      comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control
      subjects without a family history of ADPKD completed the same imaging protocol.
      We analyzed 110 at-risk subjects whose disease status was unequivocally defined
      by molecular testing and 45 unaffected healthy control subjects. Using a total of
      >10 cysts as a test criterion in subjects younger than 30 years of age, we found
      that MRI provided both a sensitivity and specificity of 100%. Comparison of our
      results from HR US with those from a previous study of conventional US using the
      test criterion of a total of three or more cysts found a higher diagnostic
      sensitivity (approximately 97% versus approximately 82%) with a slightly
      decreased specificity (approximately 98% versus 100%) in this study. Similar
      results were obtained in test subjects between the ages of 30 and 40 years old.
      These results suggest that MRI is highly sensitive and specific for diagnosis of
      ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is
      both center- and operator-dependent. 

PMID- 25074510
TI  - Control over spinal nociception as quantified by the nociceptive flexor reflex
      (RIII reflex) can be achieved under feedback of the RIII reflex.
AB  - BACKGROUND: Descending pain modulatory systems control transmission of
      nociceptive information at the spinal level, and their activity can be modified
      by cognitive and emotional processes. Thus, it may be possible to learn using
      cognitive-emotional strategies to specifically target descending pathways in
      order to achieve pain reduction. METHODS: The present study used visual feedback
      of the nociceptive flexor reflex (RIII reflex) to train healthy subjects over
      three sessions to reduce their spinal nociception (RIII reflex size) by self
      selected cognitive-emotional strategies. The study included two feedback groups
      (fixed vs. random stimulation intervals) and a control group without feedback (15
      subjects each). RESULTS: While all three groups successfully reduced their RIII
      reflexes (p < 0.01), reductions were larger in the feedback groups (p < 0.05).
      Success increased over training sessions in the feedback groups (p < 0.05). In
      the third session, RIII was reduced to 90 +/- 15% of baseline in the control
      group, and to 72 +/- 24 and 66 +/- 22% in the feedback groups. Most subjects used
      mental imagery or relaxation to achieve RIII reduction. Pain reduction correlated
      with RIII reduction in the feedback groups, but was not significantly different
      between feedback and control groups. CONCLUSIONS: The present results suggest
      that healthy subjects are able to learn using cognitive and emotional strategies
      to reduce their spinal nociception under feedback of their RIII reflex size.
      However, future studies will have to include a sham feedback group to
      differentiate true learning effects from expectancy effects induced by the
      feedback procedure.

PMID- 25074511
TI  - Articulatory-acoustic vowel space: application to clear speech in individuals
      with Parkinson's disease.
AB  - BACKGROUND/PURPOSE: Individuals with Parkinson disease (PD) often exhibit
      decreased range of movement secondary to the disease process, which has been
      shown to affect articulatory movements. A number of investigations have failed to
      find statistically significant differences between control and disordered groups,
      and between speaking conditions, using traditional vowel space area measures. The
      purpose of the current investigation was to evaluate both between-group (PD
      versus control) and within-group (habitual versus clear) differences in
      articulatory function using a novel vowel space measure, the articulatory
      acoustic vowel space (AAVS). METHODS: The novel AAVS is calculated from
      continuously sampled formant trajectories of connected speech. In the current
      study, habitual and clear speech samples from twelve individuals with PD along
      with habitual control speech samples from ten neurologically healthy adults were
      collected and acoustically analyzed. In addition, a group of listeners completed
      perceptual rating of speech clarity for all samples. RESULTS: Individuals with PD
      were perceived to exhibit decreased speech clarity compared to controls.
      Similarly, the novel AAVS measure was significantly lower in individuals with PD.
      In addition, the AAVS measure significantly tracked changes between the habitual
      and clear conditions that were confirmed by perceptual ratings. CONCLUSIONS: In
      the current study, the novel AAVS measure is shown to be sensitive to disease
      related group differences and within-person changes in articulatory function of
      individuals with PD. Additionally, these data confirm that individuals with PD
      can modulate the speech motor system to increase articulatory range of motion and
      speech clarity when given a simple prompt. LEARNING OUTCOMES: The reader will be
      able to (i) describe articulatory behavior observed in the speech of individuals
      with Parkinson disease; (ii) describe traditional measures of vowel space area
      and how they relate to articulation; (iii) describe a novel measure of vowel
      space, the articulatory-acoustic vowel space and its relationship to articulation
      and the perception of speech clarity.

PMID- 25074512
TI  - Governing through community-based research: lessons from the Canadian HIV
      research sector.
AB  - The "general public" and specific "communities" are increasingly being integrated
      into scientific decision-making. This shift emphasizes "scientific citizenship"
      and collaboration between interdisciplinary scientists, lay people, and multi
      sector stakeholders (universities, healthcare, and government). The objective of
      this paper is to problematize these developments through a theoretically informed
      reading of empirical data that describes the consequences of bringing together
      actors in the Canadian HIV community-based research (CBR) movement. Drawing on
      Foucauldian "governmentality" the complex inner workings of the impetus to
      conduct collaborative research are explored. The analysis offered surfaces the
      ways in which a formalized approach to CBR, as promoted through state funding
      mechanisms, determines the structure and limits of engagement while
      simultaneously reinforcing the need for finer grained knowledge about
      marginalized communities. Here, discourses about risk merge with notions of
      "scientific citizenship" to implicate both researchers and communities in a
      process of governance.

PMID- 25074513
TI  - Can education rescue genetic liability for cognitive decline?
AB  - Although there is a vast literature linking education and later health outcomes,
      the mechanisms underlying these associations are relatively unknown. In the
      spirit of some medical literature that leverages developmental abnormalities to
      understand mechanisms of normative functioning, we explore the ability of higher
      educational attainments to "rescue" biological/genetic liabilities in brain
      function through inheritance of a variant of the APOE gene shown to lead to
      cognitive decline, dementia, and Alzheimer's disease in old age. Deploying a
      between-sibling design that allows quasi-experimental variation in genotype and
      educational attainment within a standard gene-environment interaction framework,
      we show evidence that the genetic effects of the "risky" APOE variant on old-age
      cognitive decline are absent in individuals who complete college (vs. high school
      graduates). Auxiliary analyses suggest that the likely mechanisms of education
      are most consistent through changing brain processes (i.e., "how we think") and
      potentially building cognitive reserves, rather than alleviating old age
      cognitive decline through the channels of higher socioeconomic status and
      resources over the life course. 

PMID- 25074514
TI  - Loss of the Mexican American survival advantage after ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Mexican Americans (MAs) were previously found to have
      lower mortality after ischemic stroke than non-Hispanic whites. We studied
      mortality trends in a population-based design. METHODS: Active and passive
      surveillance were used to find all ischemic stroke cases from January 2000 to
      December 2011 in Nueces County, TX. Deaths were ascertained from the Texas
      Department of Health through December 31, 2012. Cumulative 30-day and 1-year
      mortality adjusted for covariates was estimated using log-binomial models with a
      linear term for year of stroke onset used to model time trends. Models used data
      from the entire study period to estimate adjusted mortality among stroke cases in
      2000 and 2011 and to calculate projected ethnic differences. RESULTS: There were
      1974 ischemic strokes among non-Hispanic whites and 2439 among MAs. Between 2000
      and 2011, model estimated mortality declined among non-Hispanic whites at 30 days
      (7.6% to 5.6%; P=0.24) and 1 year (20.8% to 15.5%; P=0.02). Among MAs, 30-day
      model estimated mortality remained stagnant at 5.1% to 5.2% (P=0.92), and a
      slight decline from 17.4% to 15.3% was observed for 1-year mortality (P=0.26).
      Although ethnic differences in 30-day (P=0.01) and 1-year (P=0.06) mortality were
      apparent in 2000, they were not so in 2011 (30-day mortality, P=0.63; 1-year
      mortality, P=0.92). CONCLUSIONS: Overall, mortality after ischemic stroke has
      declined in the past decade, although significant declines were only observed for
      non-Hispanic whites and not MAs at 1 year. The survival advantage previously
      documented among MAs vanished by 2011. Renewed stroke prevention and treatment
      efforts for MAs are needed.

PMID- 25074515
TI  - Education level and inequalities in stroke reperfusion therapy: observations in
      the Swedish stroke register.
AB  - BACKGROUND AND PURPOSE: Previous studies have revealed inequalities in stroke
      treatment based on demographics, hospital type, and region. We used the Swedish
      Stroke Register (Riksstroke) to test whether patient education level is
      associated with reperfusion (either or both of thrombolysis and thrombectomy)
      treatment. METHODS: We included 85 885 patients with ischemic stroke aged 18 to
      80 years registered in Riksstroke between 2003 and 2009. Education level was
      retrieved from Statistics Sweden, and thrombolysis, thrombectomy, patient, and
      hospital data were obtained from Riksstroke. We used multivariable logistic
      regression to analyze the association between reperfusion therapy and patient
      education. RESULTS: A total of 3649 (4.2%) of the patients received reperfusion
      therapy. University-educated patients were more likely to be treated (5.5%) than
      patients with secondary (4.6%) or primary education (3.6%; P<0.001). The
      inequality associated with education was still present after adjustment for
      patient characteristics; university education odds ratio, 1.14; 95% confidence
      interval, 1.03 to 1.26 and secondary education odds ratio, 1.08; 95% confidence
      interval, 1.00 to 1.17 compared with primary education. Higher hospital
      specialization level was also associated with higher reperfusion levels
      (P<0.001). In stratified multivariable analyses by hospital type, significant
      treatment differences by education level existed only among large nonuniversity
      hospitals (university education odds ratio, 1.20; 95% confidence interval, 1.04
      1.40; secondary education odds ratio, 1.14; 95% confidence interval, 1.01-1.29).
      CONCLUSIONS: We demonstrated a social stratification in reperfusion, partly
      explained by patient characteristics and the local hospital specialization level.
      Further studies should address treatment delays, stroke knowledge, and means to
      improve reperfusion implementation in less specialized hospitals.

PMID- 25074516
TI  - Implication of left ventricular diastolic dysfunction in cryptogenic ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Left ventricular diastolic dysfunction (LVDD) is a
      predictor for atrial fibrillation (AF). This study was aimed to investigate
      whether LVDD in cryptogenic ischemic stroke (CS) could be a clue to stroke
      mechanism. METHODS: The clinical and echocardiographic findings of 1589
      consecutive patients with acute ischemic stroke or transient ischemic attack
      between 2004 and 2013 were reviewed. LVDDs among stroke subtypes were graded by
      transthoracic echocardiography into 4 groups by severity: normal, abnormal
      relaxation (grade I), pseudonormal (grade II), and restrictive diastolic filling
      (grade III), whereas severe LVDD was defined as grade III. We classified the
      lesion pattern of CS into cardioembolism-mimic or non-cardioembolism-mimic and
      determined whether cardioembolism-mimic lesions were associated with severe LVDD.
      RESULTS: The fraction of severe LVDD in CS was not different from that of stroke
      with AF (27.3% versus 37.1%; P=0.173) but was significantly higher than that of
      stroke without AF (27.3% versus 13.4%; P=0.008). Cardioembolism-mimic CS had more
      severe LVDD than non-cardioembolism-mimic CS (41.4% versus 11.5%; P=0.013). LVDD
      of grade II (odds ratio, 4.37; 95% confidence interval, 2.99-6.41) and grade III
      (odds ratio, 5.60; 95% confidence interval, 3.42-9.17) were independently related
      to stroke with AF after adjusting covariates. CONCLUSIONS: The severe LVDD could
      be a predictor of stroke with AF, and its frequency was similar between CS and
      stroke with AF. Cardioembolism-mimic CS had significantly more severe LVDD than
      non-cardioembolism-mimic CS. LVDD could be helpful to discriminate the stroke
      mechanism in the patients with acute CS.

PMID- 25074518
TI  - Are cognitive screening tools sensitive and specific enough for use after stroke?
      A systematic literature review.

PMID- 25074517
TI  - Thrombolysis in ischemic stroke without arterial occlusion at presentation.
AB  - BACKGROUND AND PURPOSE: None of the randomized trials of intravenous tissue-type
      plasminogen activator reported vascular imaging acquired before thrombolysis.
      Efficacy of tissue-type plasminogen activator in stroke without arterial
      occlusion on vascular imaging remains unknown and speculative. METHODS: We
      performed a retrospective, multicenter study to collect data of patients who
      presented to participating centers during a 5-year period with ischemic stroke
      diagnosed by clinical examination and MRI and with imaging evidence of no
      vascular occlusion. These patients were divided into 2 groups: those who received
      thrombolytic therapy and those who did not. Primary outcome measure of the study
      was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90
      days from stroke onset. Secondary outcome measures were good clinical outcome
      (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0).
      Safety outcome measures were incidence of symptomatic intracerebral hemorrhage
      and poor outcome (modified Rankin Scale, 4-6). RESULTS: A total of 256 patients
      met study criteria, 103 with thrombolysis and 153 without. Logistic regression
      analysis showed that patients who received thrombolysis had more frequent
      excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral
      hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04).
      Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds
      ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds
      ratio 8.25 (P<0.01). CONCLUSIONS: This study provides crucial data that patients
      with ischemic stroke who do not have visible arterial occlusion at presentation
      may benefit from thrombolysis.

PMID- 25074519
TI  - Maternal anxiety, risk factors and parenting in the first post-natal year.
AB  - BACKGROUND: The antecedents and consequences of maternal post-natal anxiety have
      received comparatively less attention than depression despite being one of the
      most frequently reported mental health difficulties experienced by parents
      following childbirth. The aim of this study was to extend emerging literature on
      post-natal anxiety by investigating the prevalence of maternal anxiety symptoms,
      and its relationship with parenting behaviours (i.e. warmth, hostility) and
      experiences (i.e. parenting efficacy and satisfaction) within the first post
      natal year. The psychosocial risk factors for post-natal anxiety symptoms were
      also explored. METHODS: A community sample of 224 Australian mothers of infants
      (aged 0-12 months) completed a self-report questionnaire. RESULTS: Mothers in the
      current sample reported significantly more symptoms of anxiety compared with a
      normative sample. Approximately 18% of mothers reported mild to extremely severe
      symptoms of anxiety, with a high proportion experiencing co-morbid depressive
      symptoms. Maternal anxiety was associated with low parenting warmth, involvement,
      efficacy and satisfaction, and high parenting hostility. Yet, co-morbid
      depression and anxiety was more strongly associated with these parenting
      behaviours and experiences than anxiety alone. CONCLUSION: A range of
      psychosocial risk factors (e.g. education, sleep, relationship quality) were
      associated with maternal post-natal anxiety symptoms, providing opportunities for
      early identification and targeted early intervention.

PMID- 25074520
TI  - Executive functioning and adaptive coping in healthy adults.
AB  - Middle-aged individuals encounter multiple environmental demands to which they
      must develop efficient solutions, thus making the study of executive functions
      and coping strategies within this age group important. This study evaluated the
      relationship between the planning and flexible organization of executive function
      with adaptive coping strategies (ACS) in adults aged 43 to 52 years old. The
      study included 104 participants, including 52 men and 52 women, with no history
      of neurological or psychiatric illnesses, diabetes, or hypertension. The
      participants engaged in the Tower of London(DX) (TOL(DX)) test, the Wisconsin
      Card-Sorting Test (WCST), and the Coping Strategies Inventory. A relationship was
      observed between the percentage of errors and conceptual-level responses (WCST)
      and the Problem Solving ACS. In a separate analysis performed on the men, a
      negative relationship was discovered between the WCST and the Emotional
      Expression ACS. In the female group, the dimensions of the WCST and the TOL(DX)
      were associated with the ACS Emotional Expression and Problem-Solving subscales
      and the maladaptive coping strategy Social Withdrawal subscale. The relationship
      between executive functioning and the ACS is multidimensional, complex, and
      different between men and women. This study adds a neuropsychological
      characterization of the relationship between executive functions and ACS with
      ecological validity. The study confirms a relationship between the flexible
      organization of executive function and the Problem-Solving ACS. 

PMID- 25074522
TI  - Intravenous iron and safety: is the end of the debate on the horizon?

PMID- 25074521
TI  - Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for
      targeting breast cancer tumors.
AB  - Active targeting of nanoparticles to receptor-overexpressing cancer cells has
      great potential for enhancing the cellular uptake of nanoparticles and for
      reducing fast clearance of the nanoparticles from the body. Herein, we present a
      preparation method of a porous silicon (PSi)-based nanodelivery system for breast
      cancer targeting, by covalently conjugating a synthesized amide-modified
      hyaluronic acid (HA(+)) derived polymer on the surface of undecylenic acid
      modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting
      UnTHCPSi-HA(+) nanoparticles showed relatively small size, reduced
      polydispersibility, high biocompatibility, improved colloidal and human plasma
      stability, as well as enhanced cellular interactions and internalization.
      Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi
      HA(+) relies on the capability of the conjugated HA(+) to bind and consequently
      target CD44 receptors expressed on the surface of breast cancer cells, thus
      making the HA(+)-functionalized UnTHCPSi nanoparticles a suitable and promising
      nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug
      delivery. 

PMID- 25074523
TI  - Clinical effectiveness and comparative hospital costs of different platelet dose
      strategies.

PMID- 25074524
TI  - Achieving and maintaining an optimal trough level for prophylaxis in haemophilia:
      the past, the present and the future.

PMID- 25074525
TI  - Ibuprofen-induced extensive toxic epidermal necrolysis - a multidisciplinary
      therapeutic approach in a single case.

PMID- 25074526
TI  - Spontaneous thrombosis in a patient with factor XI deficiency homozygous for the
      p.Cys398Tyr mutation.

PMID- 25074527
TI  - Genetic association of BSF2 polymorphism and susceptibility to lung cancer.
AB  - BSF2 polymorphism is believed to affect the transcriptional capability of the
      gene. Studies of lung cancer have associated BSF2 polymorphism with risk of lung
      cancer, only failing to identify whether this polymorphism predisposes an
      individual variation in the susceptibility to the malignant cancer. The primary
      aim of this study was to determine the association. An exhaustive literature
      search was conducted in the Medline and CNKI databases. Based on the data
      extracted from each of the included studies, we estimated the risk of lung cancer
      ascribed to BSF2 polymorphism by calculating ORs and its 95 % CIs. When pooling
      all eligible studies into the meta-analysis, we did not see any evidence
      suggesting there was a significant association between BSF2 polymorphism and risk
      of lung cancer. For the studies of Caucasian sample, the effects were exactly the
      same as those observed in the overall comparison. Our results suggest that BSF2
      polymorphism may not predispose genetic susceptibility toward lung cancer in
      Caucasian populations, which nevertheless requires additional investigation.

PMID- 25074528
TI  - rs3746444 polymorphism and susceptibility to hepatocellular carcinoma: evidence
      from published studies.
AB  - The present study was undertaken to quantitatively evaluate the association
      between rs3746444 polymorphism and HCC risk. In this analysis with 667 cancer
      cases and 1,006 control subjects, we summarized 4 eligible case-control studies
      by searching databases of PubMed, EMBASE, and CNKI. The strength of the
      association was assessed by calculating odds ratios (ORs) with 95 % confidence
      intervals (CIs) with the fixed-effects model. We found that neither the allele
      frequency nor genotype distribution of this polymorphism was associated with risk
      of HCC in any genetic model. Similarly, no associations were suggested either in
      subgroup analyses by ethnicity or by source of control. Our research suggested
      that rs3746444 polymorphism may not be a risk factor for HCC. However, well
      designed studies with a larger sample size are needed to confirm these findings.

PMID- 25074530
TI  - The significance and mechanism of propofol on treatment of ischemia reperfusion
      induced lung injury in rats.
AB  - This study is aimed to investigate the efficacy and underlying the mechanism of
      propofol in treatment of ischemia reperfusion (IR)-induced lung injury in rats,
      providing a novel insight of therapeutic strategy for IR-induced lung injury. 120
      healthy SD rats were selected and randomly divided into sham operation group, IR
      group, and propofol group (40 rats per group). Bronchoalveolar lavage fluid
      (BALF) protein content, serum protein content, lung permeability index, lung
      water content rate, methane dicarboxylic aldehyde (MDA) in lung tissue,
      superoxide dismutase (SOD), nitric oxide (NO), endothelin (ET-1), toll-like
      receptor 4 (TLR4), nuclear factor (NF-kappaB), and tumor necrosis factor-alpha
      (TNF-alpha) were examined and compared among different groups to evaluate the
      therapeutical effects of propofol on IR-induced lung injury and analyze the
      mechanism. In sham operation group, neither change in lung tissue nor pulmonary
      interstitial edema or alveolar wall damage was found under microscope; in IR
      group, marked pulmonary interstitial edema and alveolar wall damage complicated
      with inflammatory cell infiltration and hemorrhage were found; in propofol group,
      alveolar wall widening was observed, however, hemorrhage in alveolar cavity,
      inflammatory infiltration and tissue damage were less significant than in IR
      group. At 3 h after reperfusion, BALF protein content, lung permeability index,
      and lung water content rate were all significantly increased in IR group and
      propofol group, while the serum protein content was significantly lower than sham
      operation group (p < 0.05). Moreover, we found that the change of above
      parameters in propofol group was less significant than in IR group (p < 0.05). No
      statistically significant difference was found in ET-1 levels in different groups
      (p > 0.05). In contrast, MDA and NO in IR group and propofol group were
      significantly increased, while SOD activity was significantly decreased (p <
      0.05). Furthermore, the change of above parameters in propofol group was less
      significant than in IR group (p < 0.05). In addition, mRNAs of TLR4, NF-kappaB,
      and TNF-alpha were significantly increased in IR group and propofol group (p <
      0.05) with more significant change in IR group compared with propofol group (p <
      0.05). Propofol has protective effects against IR-induced lung injury by
      improving activity of oxygen radical and restoring NO/ET-1 dynamic balance.
      Besides, regulation of TLR4, NF-kappaB, and TNF-alpha by propofol also play
      important role in alleviating IR-induced lung injury.

PMID- 25074529
TI  - Genetic association between AGPHD1 variant and lung cancer risk.
AB  - The knowledge of molecular mechanism that underlies the genetic predisposition to
      lung cancer is yet limited. Results from previous studies addressing the
      association of AGPHD1 variant rs8034191 with lung carcinogenesis remain
      inconclusive. Herein, we combined these data and re-examined the association. We
      performed a meta-analysis of Asian studies identified through various ways. Using
      the data collected from each eligible study, we combined the effect estimates
      (ORs and its 95 % CIs) with the fixed effects model (Mantel-Haenszel method).
      Statistical analyses were done using STATA software. Data from nine studies
      (29,290 subjects) carried out in Asian populations were analyzed in this work.
      There was no overall association between variant rs8034191 and lung cancer risk
      under the allele frequency model (OR = 1.03, 95 % CI = 0.93-1.13, P heterogeneity
      = 0.522). We observed the same associations under other genetic models and in the
      subgroup analyses by ethnicity and smoking status. Our results indicate that
      variant rs8034191 in the AGPHD1 gene may not modify the genetic risk of lung
      cancer in Asian populations.

PMID- 25074531
TI  - Ultrasound B-mode and elastographic findings of mixed tumour of the skin on the
      scalp.

PMID- 25074532
TI  - [Utility of beta-blockers in patients with ischemic heart disease undergoing non
      cardiac surgery. Commentary].

PMID- 25074533
TI  - Therapeutic strategy for ductal carcinoma in situ patients according to Van Nuys
      Prognostic Index.
AB  - AIM: Evaluation of therapeutic strategy for Ductal Carcinoma In Situ (DCIS)
      patients at our Brest Cancer Centre and analysis of our pattern of treatment with
      respect to Van Nuys Prognostic Index (VNPI) cathegories. MATHERIAL OF STUDY: Our
      study population is the result of a selection of 85 DCIS patients classified
      according to the VNPI risk of Local Recurrence (LR). A comparison was made
      between treatment effectively performed and therapy suggested by VNPI protocols.
      RESULTS: Out of 53 DCIS women (62%) at low local recurrence risk, 5 patients
      underwent Breast Conserving Surgery (BCS) alone, 7 were treated with mastectomy
      and 41 underwent BCS followed by radiotherapy (RT). Out of 31 patients (37%)
      belonging to VNPI intermediate risk group, 25 cases recived BCS+RT and 6 cases
      received mastectomy. Only one patient (1%) belonged to VNPI high risk group and
      underwent mastectomy. DISCUSSION: Only 31 patients (36,5%) had their definitive
      treatment according to recommended VNPI criteria, but none of the other 54 cases
      (63,5%) was undertreated. Performing mastectomy instead of BCS or adding adjuvant
      radiotherapy at BCS alone were not considered overtreatment because the
      therapeutic strategy was the result of a multidisciplinary discussion.
      CONCLUSION: As DCIS is a heterogeneus desease the one-size-fits-all approach to
      treatment seems inappropriate. The VNPI was developed in order to help treatment
      choices, but therapeutic strategies can't be based only on local recurrence risk
      and need a multidisciplinary approach. KEY WORDS: Breast cancer, Ductal carcinoma
      in situ, Van Nuys Prognostic Index.

PMID- 25074536
TI  - Making our health and care systems fit for an ageing population: David Oliver,
      Catherine Foot, Richard Humphries. King's Fund March 2014.

PMID- 25074537
TI  - Understanding vitamin D deficiency.

PMID- 25074538
TI  - National Osteoporosis Society vitamin D guideline summary.
AB  - The National Osteoporosis Society (NOS) published its document, Vitamin D and
      Bone Health: A Practical Clinical Guideline for Patient Management, in 2013 as a
      practical clinical guideline on the management of vitamin D deficiency in adult
      patients with, or at risk of developing, bone disease. There has been no clear
      consensus in the UK on vitamin D deficiency its assessment and treatment, and
      clinical practice is inconsistent. This guideline is aimed at clinicians,
      including doctors, nurses and dieticians. It recommends the measurement of serum
      25 (OH) vitamin D (25OHD) to estimate vitamin D status in the following clinical
      scenarios: bone diseases that may be improved with vitamin D treatment; bone
      diseases, prior to specific treatment where correcting vitamin D deficiency is
      appropriate; musculoskeletal symptoms that could be attributed to vitamin D
      deficiency. The guideline also states that routine vitamin D testing is
      unnecessary where vitamin D supplementation with an oral antiresorptive treatment
      is already planned and sets the following serum 25OHD thresholds: <30 nmol/l is
      deficient; 30-50 nmol/l may be inadequate in some people; >50 nmol/l is
      sufficient for almost the whole population. For treatment, oral vitamin D3 is
      recommended with fixed loading doses of oral vitamin D3 followed by regular
      maintenance therapy when rapid correction of vitamin D deficiency is required,
      although loading doses are not necessary where correction of deficiency is less
      urgent or when co-prescribing with an oral antiresorptive agent. For monitoring,
      serum calcium (adjusted for albumin) should be checked 1 month after completing a
      loading regimen, or after starting vitamin D supplementation, in case primary
      hyperparathyroidism has been unmasked. However, routine monitoring of serum 25OHD
      is generally unnecessary but may be appropriate in patients with symptomatic
      vitamin D deficiency or malabsorption and where poor compliance with medication
      is suspected. The guideline focuses on bone health as, although there are
      numerous putative effects of vitamin D on immunity modulation, cancer prevention
      and the risks of cardiovascular disease and multiple sclerosis, there remains
      considerable debate about the evaluation of extraskeletal factors and optimal
      vitamin D status in these circumstances. 

PMID- 25074539
TI  - Anti-NMDA receptor encephalitis and Facklamia languida septicaemia: initially
      unpronounceable but eventually treatable.

PMID- 25074540
TI  - Tumor cells in search for glutamate: an alternative explanation for increased
      invasiveness of IDH1 mutant gliomas.

PMID- 25074541
TI  - Nitroxoline induces apoptosis and slows glioma growth in vivo.
AB  - BACKGROUND: Nitroxoline is an FDA-approved antibiotic with potential antitumor
      activity. Here we evaluated whether nitroxoline has antiproliferative properties
      on glioma cell growth in vitro and in vivo using glioma cell lines and a
      genetically engineered PTEN/KRAS mouse glioma model. METHODS: The effect of
      nitroxoline treatment on U87 and/or U251 glioma cell proliferation, cell-cycle
      arrest, invasion, and ability to induce an apoptotic cascade was determined in
      vitro. Magnetic resonance imaging was used to measure glioma volumes in
      genetically engineered PTEN/KRAS mice prior to and after nitroxoline therapy.
      Induction of apoptosis by nitroxoline was evaluated at the end of treatment using
      terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick
      end labeling (TUNEL). RESULTS: Nitroxoline inhibited the proliferation and
      invasion of glioblastoma cells in a time- and dose-dependent manner in vitro.
      Growth inhibition was associated with cell-cycle arrest in G1/G0 phase and
      induction of apoptosis via caspase 3 and cleaved poly(ADP-ribose) polymerase. In
      vivo, nitroxoline-treated mice had no increase in tumor volume after 14 days of
      treatment, whereas tumor volumes doubled in control mice. Histological
      examination revealed 15%-20% TUNEL-positive cells in nitroxoline-treated mice,
      compared with ~5% in the control group. CONCLUSION: Nitroxoline induces apoptosis
      and inhibits glioma growth in vivo and in vitro. As an already FDA-approved
      treatment for urinary tract infections with a known safety profile, nitroxoline
      could move quickly into clinical trials pending confirmatory studies.

PMID- 25074542
TI  - Molecular cytogenetic characterization of mammary neuroendocrine carcinoma.
AB  - Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that
      accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of
      the breast is an aggressive subtype of mammary carcinoma that is distinct from
      invasive ductal carcinoma, not otherwise specified, and have suggested that these
      tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise
      specified. In this study, we provide the first cytogenetic characterization of
      mammary NEC using both conventional G-banding and spectral karyotype on a group
      of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases,
      with 4 of them showing complex karyotypes. Of these, recurrent numerical
      aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n =
      2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n
      = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex
      karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to
      hundreds of genomic rearrangements occur in a one-off cellular crisis. One of
      these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The
      other also had evidence of chromosome 8 chromothripsis, making this a recurrent
      finding shared by both cases. We also found that mammary NEC shared some
      cytogenetic abnormalities--such as trisomy 7 and 12--with other neuroendocrine
      tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as
      potential common molecular aberrations in neuroendocrine tumors. To our
      knowledge, this is the first report on molecular cytogenetic characterization of
      mammary NEC.

PMID- 25074543
TI  - Immunohistochemistry versus next-generation sequencing for the routine detection
      of BRAF V600E mutation in melanomas.

PMID- 25074544
TI  - A fluorogenic heterogeneous immunoassay for cardiac muscle troponin cTnI on a
      digital microfluidic device.
AB  - We describe a fluorogenic two-site noncompetitive heterogeneous immunoassay with
      magnetic beads on a low-voltage digital microfluidic platform using closed
      electrowetting-on-dielectric (EWOD). All the steps of an enzyme-linked
      immunosorbent assay (ELISA) were performed on the device using 9H-(1, 3-dichloro
      9, 9-dimethylacridin-2-one-7-yl) phosphate as the fluorogenic substrate for the
      enzyme alkaline phosphatase. The performance of the system was demonstrated with
      cardiac marker Troponin I (cTnI) as a model analyte in phosphate-buffered saline
      samples. cTnI was detected within the diagnostically relevant range with a limit
      of detection of 2.0 ng/mL (CV = 6.47 %). Washing of magnetic beads was achieved
      by movement through a narrow region of buffer bridging one drop to another with
      minimal fluid transfer. More than 90 % of the unbound reagents were removed after
      five washes. Further experiments testing human blood serum on the same platform
      demonstrated a sample-to-answer time at ~18.5 min detecting 6.79 ng/mL cTnI. 

PMID- 25074545
TI  - Glycation sites of human plasma proteins are affected to different extents by
      hyperglycemic conditions in type 2 diabetes mellitus.
AB  - Glucose can modify proteins in human blood, forming early glycation products
      (e.g., Amadori compounds), which can slowly degrade to advanced glycation
      endproducts (AGEs). AGEs contribute significantly to complications of diabetes
      mellitus and, thus, represent markers of advanced disease stages. They are,
      however, currently unsuitable for early diagnosis and therapeutic monitoring.
      Here, we report sensitive strategies to identify and relatively quantify protein
      glycation sites in human plasma samples obtained from type 2 diabetes mellitus
      (T2DM) patients and age-matched nondiabetic individuals using a bottom-up
      approach. Specifically, Amadori peptides were enriched from tryptic digests by
      boronic acid affinity chromatography, separated by reversed-phase chromatography,
      and analyzed on-line by high-resolution mass spectrometry. Among the 52 Amadori
      peptides studied here were 20 peptides resembling 19 glycation sites in six human
      proteins detected at statistically significantly higher levels in T2DM than in
      the normoglycemic controls. Four positions appeared to be unique for T2DM within
      the detection limit. All 19 glycation sites represent promising new biomarker
      candidates for early diagnosis of T2DM and adequate therapeutic control, as they
      may indicate early metabolic changes preceding T2DM. 

PMID- 25074546
TI  - A novel approach using electrospray ionization mass spectrometry to study
      competitive binding of small molecules with mixed DNA sequences.
AB  - Minor groove binding compounds have been shown to induce changes in global DNA
      conformation, allosterically inhibiting DNA-protein interactions necessary for
      transcriptional processes. Many minor groove binders are specific for AT base
      pairs but have little preference over alternating AT or A-tract sequences. Few
      compounds, other than polyamides, show selectivity for mixed sequences with AT
      and GC base pairs. Electrospray ionization mass spectrometry (ESI-MS) can provide
      insight on the stoichiometry and relative affinities in minor groove recognition
      of different DNA sequences with a library of minor groove binders. A goal in our
      current research is to develop new compounds that recognize mixed sequences of
      DNA. In an effort to optimize screening for compounds that target mixed AT and GC
      base pair sequences of DNA, ESI-MS was used to study the competitive binding of
      compounds with a mixed set of DNA sequences. The method identified preferred
      binding sites, relative affinities, and concentration-dependent binding
      stoichiometry for the minor groove binding compounds netropsin and DB75 with AT
      rich sequences and DB293 with ATGA and AT sites. 

PMID- 25074548
TI  - xMAP-based analysis of three most prevalent staphylococcal toxins in
      Staphylococcus aureus cultures.
AB  - Detection of staphylococcal toxins presents a great interest for medical
      diagnostics. Screening of clinical samples for the presence of several types of
      staphylococcal toxins using traditional methods-biological tests on animals or
      cell cultures as well as ELISA-is laborious. Multiplex detection methods would
      simplify testing. We have designed an xMAP-based assay to detect three
      staphylococcal toxins-enterotoxins A and B (SEA and SEB) and toxic shock syndrome
      toxin (TSST)-in cultural supernatants obtained from different strains of
      Staphylococcus aureus. The limits of detection of SEA, SEB, and TSST multiplex
      detection in S. aureus growth medium were 10, 1,000, and 5 pg/mL, respectively.
      Fifty-nine samples of S. aureus cultural supernatants were tested with the xMAP
      assay. The developed assay has proved highly effective detection of the natural
      toxins in the samples obtained due to bacterial cells cultivation. In prospect,
      the developed test system can be used in clinical diagnostics and in monitoring
      of foodstuffs and environmental objects. 

PMID- 25074549
TI  - UV-polymerized butyl methacrylate monoliths with embedded carboxylic single
      walled carbon nanotubes for CEC applications.
AB  - The preparation of polymeric monoliths with embedded carboxy-modified single
      walled carbon nanotubes (c-SWNTs) and their use for capillary
      electrochromatography (CEC) is described. Carbon nanotube composites were
      obtained by preparing a polymerization mixture in the presence of increasing c
      SWNT concentrations, followed by UV initiation. The novel stationary phases were
      studied by optical microscopy, scanning electron microscopy (SEM), transmission
      electron microscopy (TEM) and Raman spectroscopy. Using short UV-polymerization
      times, the optimized porogenic solvent (a binary mixture of 1,4-butanediol and 2
      propanol) gave rise to polymeric beds with homogenously dispersed embedded c
      SWNTs. The CEC features of these monoliths were evaluated using polycyclic
      aromatic hydrocarbons (PAHs), non-steroidal anti-inflammatory drugs (NSAIDs) and
      chiral compounds. The monolith prepared in the presence of c-SWNTs showed
      enhanced resolution of the text mixtures, including a remarkable capability to
      separate enantiomers. 

PMID- 25074550
TI  - Comparative characterization of GmSPX members reveals that GmSPX3 is involved in
      phosphate homeostasis in soybean.
AB  - BACKGROUND AND AIMS: Proteins containing the SPX (SYG1/Pho81/XPR1) domain are
      vital components in the phosphorus (P) signalling pathway, and regulate phosphate
      (Pi) homeostasis in plants. However, the characteristics and functions of GmSPX
      members in soybean (Glycine max) remain largely unknown. METHODS: BLAST searching
      revealed nine GmSPX members in the soybean genome. Subsequently, expression
      patterns of GmSPX members were investigated in various tissues of soybean grown
      in nutrient solution or sand culture through quantitative real-time PCR (qPCR)
      analysis. Sub-cellular localization of GmSPX was examined via transient
      expression of 35S:GmSPX-GFP in epidermal cells of onion (Allium cepa). Finally,
      soybean transgenic composite plants were generated to study GmSPX3 functions. KEY
      RESULTS: Nine GmSPX members were identified, which were classified into three
      groups based on phylogenetic analysis. Diverse responses of GmSPX members to
      deficiencies of nutrients (nitrogen, phosphorus, potassium and iron) or
      inoculation of arbuscular mycorrhizal fungi and rhizobia were observed in
      soybean. In addition, variations of sub-cellular localization of GmSPX members
      were found. Among them, GmSPX3, GmSPX7 and GmSPX8 were localized in the nuclei,
      and the other GmSPX members were confined to the nuclei and cytoplasm. The
      nuclear-localized and Pi starvation responsive-gene, GmSPX3, was functionally
      analysed in soybean transgenic composite plants. Overexpression of GmSPX3 led to
      increased P concentrations in both shoots and roots in the high-P treatment, and
      increased transcription of seven Pi starvation-responsive genes in soybean hairy
      roots. CONCLUSIONS: Taken together, the results suggest that GmSPX3 is a positive
      regulator in the P signalling network, and controls Pi homeostasis in soybean.

PMID- 25074551
TI  - Learning from nature: binary cooperative complementary nanomaterials.
AB  - In this Review, nature-inspired binary cooperative complementary nanomaterials
      (BCCNMs), consisting of two components with entirely opposite physiochemical
      properties at the nanoscale, are presented as a novel concept for the building of
      promising materials. Once the distance between the two nanoscopic components is
      comparable to the characteristic length of some physical interactions, the
      cooperation between these complementary building blocks becomes dominant and
      endows the macroscopic materials with novel and superior properties. The first
      implementation of the BCCNMs is the design of bio-inspired smart materials with
      superwettability and their reversible switching between different wetting states
      in response to various kinds of external stimuli. Coincidentally, recent studies
      on other types of functional nanomaterials contribute more examples to support
      the idea of BCCNMs, which suggests a potential yet comprehensive range of future
      applications in both materials science and engineering. 

PMID- 25074552
TI  - miR-206 inhibits cell migration through direct targeting of the actin-binding
      protein coronin 1C in triple-negative breast cancer.
AB  - Patients with triple-negative breast cancer (TNBC) have an overall poor
      prognosis, which is primarily due to a high metastatic capacity of these tumors.
      Novel therapeutic approaches to target the signaling pathways that promote
      metastasis are desirable, in order to improve the outcome for these patients. A
      loss of function of a microRNA, miR-206, is related to increased metastasis
      potential in breast cancers but the mechanism is not known. In this study, we
      show that miR-206 was decreased in TNBC clinical tumor samples and cell lines
      whereas one of its predicted targets, actin-binding protein CORO1C, was
      increased. Expression of miR-206 significantly reduced proliferation and
      migration while repressing CORO1C mRNA and protein levels. We demonstrate that
      miR-206 interacts with the 3'-untranslated region (3'-UTR) of CORO1C and
      regulates this gene post-transcriptionally. This post-transcriptional regulation
      was dependent on two miR-206-binding sites within the 3'-UTR of CORO1C and was
      relieved by mutations of corresponding sites. Further, silencing of CORO1C
      reduced tumor cell migration and affected the actin skeleton and cell morphology,
      similar to miR-206 expression, but did not reduce proliferation. In accordance
      with this, overexpression of CORO1C rescued the inhibitory effect of miR-206 on
      cell migration. Our findings suggest that miR-206 represses tumor cell migration
      through direct targeting of CORO1C in TNBC cells which modulates the actin
      filaments. This pathway is a novel mechanism that offers a mechanistic basis
      through which the metastatic potential of TNBC tumors could be targeted. 

PMID- 25074553
TI  - Disposable devices for RIRS: where do we stand in 2013? What do we need in the
      future?
AB  - PURPOSE: Disposable devices for retrograde intrarenal surgery (RIRS) form a
      significant part of the urologist's armamentarium for the endoscopic management
      of urologic diseases. Herein, we provide an overview of the literature regarding
      the advances and controversies of these devices. METHODS: A PubMed search was
      used to identify the literature discussing the subject of disposable devices for
      RIRS. Articles published between 2012 and 2013 were considered. RESULTS: Ureteral
      access implements including access sheaths, wires, and dilators are an area of
      both improvement and controversy regarding their proper use. The safety,
      effectiveness, and limitations of lithotrites continue to be refined. Stone
      retrieval devices are undergoing persistent miniaturization, and their use may
      prove to be cost effective. The debate over perioperative stenting remains, while
      symptom management is explored. A cost-effective option for disposable flexible
      ureteroscopy shows promise. CONCLUSIONS: While rapid advances in technology and
      knowledge continue, continual improvements are necessary. Disposable equipment
      needs persistent refinement and possible miniaturization. More efficient fragment
      retrieval devices are needed. Durability of laser fibers and safety within
      ureteroscopes needs to be improved. Reducing stent morbidity remains an ongoing
      challenge. Lastly, costs need to be reduced by the further development of
      disposable flexible ureteroscopes and in the recyclability of disposable devices
      to improve availability worldwide.

PMID- 25074554
TI  - Social determinants of malnutrition among Serbian children aged <5 years: ethnic
      and regional disparities.
AB  - OBJECTIVES: To assess the association between growth indicators of Serbian
      children aged <5 years of Roma and non-Roma populations and social determinants
      of health. METHODS: This study used a cross-sectional secondary data analysis
      design to measure national and Roma population samples from the MICS 4 (UNICEF)
      performed in 2010 in Serbia. A total of 4,978 questionnaires were observed with
      children aged <5 years. Logistic regression analysis was performed to identify
      association between social determinants of health and growth indicators. RESULTS:
      Roma children were more than three times more likely to exhibit stunted and/or
      severely stunted than non-Roma children from the lowest wealth quintile. Non-Roma
      children residing outside of the Belgrade region had a lower risk of stunted
      compared to children residing within the Belgrade region, while the risk of
      stunted among Roma children was nearly twofold greater than those residing in
      southern and eastern Serbia than in the Belgrade region. CONCLUSIONS: Our
      findings clarified the necessity to establish ethnically and regionally sensitive
      programs to solve the malnutrition problems.

PMID- 25074555
TI  - The neutrophil lymphocyte ratio in coronary heart disease.

PMID- 25074556
TI  - Ticagrelor effectiveness overestimated by VASP index: platelet inhibition by
      ticagrelor versus prasugrel in acute coronary syndrome patients according to
      platelet function tests.

PMID- 25074557
TI  - Impact on myocardial reperfusion using the M-Guard stent in primary percutaneous
      coronary intervention for ST-elevation myocardial infarction.

PMID- 25074558
TI  - Oxidative stress and systemic inflammation as modifiers of cardiac autonomic
      responses to particulate air pollution.
AB  - BACKGROUND: The role of oxidative stress and systemic inflammation on the
      association between personal exposures to ambient fine particulate matter <= 2.5
      MUm in diameter (PM2.5) and cardiac autonomic dysfunction, indicated by reduction
      in heart rate variability (HRV), has not been examined. METHODS: We performed a
      repeated measures study on community adults in a densely populated inner city
      neighborhood in Boston, Massachusetts. Continuous ambulatory electrocardiogram
      (ECG) monitoring and personal exposure to PM2.5 were measured for up to two
      consecutive days. Peripheral blood and spot urine samples were collected at 12
      hour intervals for the measurements of markers of inflammation including C
      reactive protein (CRP), fibrinogen, white blood cell (WBC) and platelet counts as
      well as for the analysis of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a
      marker of oxidative DNA damage. RESULTS: After adjusting for confounders, we
      found a pronounced decrease in nighttime standard deviation of normal-to normal
      intervals (SDNN): an interquartile range (IQR) increase in PM2.5 (13.6 MUg/m(3))
      was associated with an 8.4% decrease in SDNN (95% CI: -11.3 to -5.5). Compared
      with the lower eightieth percentile, significantly greater PM2.5 associated
      nighttime SDNN reductions were observed among subjects in the upper twentieth
      percentile of 8-OHdG by -25.3%, CRP by -24.9%, fibrinogen by -28.7%, WBC by 
      23.4%, and platelet counts by -24.0% (all P<0.0001; all P interaction<0.01).
      CONCLUSIONS: These data suggest that oxidative stress and systemic inflammation
      exacerbate the adverse effects of PM2.5 on the cardiac autonomic function even at
      ambient levels of exposure.

PMID- 25074559
TI  - Tako-Tsubo cardiomyopathy and high-degree atrio-ventricular block: do we need to
      wait left ventricular function recovery to implant a pacemaker?

PMID- 25074560
TI  - Enhanced skin delivery of liquiritigenin and liquiritin-loaded liposome-in
      hydrogel complex system.
AB  - OBJECTIVE: To study the permeation of liquiritigenin (LQG) and liquiritin (LQ) as
      licorice flavonoids into the skin, we prepared ceramide liposome-in-cellulose
      hydrogel complex system. METHODS: Liposome-in-hydrogel complex systems were
      developed by incorporating ceramide liposomes into cellulose hydrogels by the
      swelling method. We evaluated their physical and chemical properties,
      encapsulation efficiency and skin permeability using Franz Diffusion Cell. It was
      visually seen by CLSM images analysis. RESULTS: The ceramide liposome, consisting
      of biocompatible lipid membranes, remained stable for over 3 weeks. Encapsulation
      efficiencies for liquiritigenin and liquiritin-loaded liposome-in-hydrogel were
      69.39% and 64.71%, respectively. Liposome-in-hydrogel complex systems (LQG:
      56.55%, LQ: 66.99%) had greater skin permeability than control (LQG: 4.92%, LQ:
      5.30%) or a single liposome systems (LQG: 43.34%, LQ: 48.97%) and hydrogel
      systems (LQG: 38.21%, LQ: 55.07%). CONCLUSION: Liposome-in-hydrogel system can be
      a potential drug delivery system for topical delivery of antioxidants such as
      licorice flavonoids to construct antioxidative skin barrier.

PMID- 25074561
TI  - Pilot early intervention antenatal group program for pregnant women with anxiety
      and depression.
AB  - This study aims to examine the acceptability and effectiveness of an antenatal
      group intervention designed to reduce the severity of depression and anxiety
      symptoms and improve maternal attachment in pregnant women with current or
      emerging depression and anxiety. Women who participated in the program completed
      pre- and posttreatment measures of depression (Centre of Epidemiological Studies
      Depression Scale) and Edinburgh Postnatal Depression Scale), anxiety (State-Trait
      Anxiety Inventory) and maternal attachment (Condon Maternal Antenatal Attachment
      Scale). Participants also completed a satisfaction questionnaire and provided
      general feedback about the group intervention and experience. A total of 48 women
      (M = 26 weeks of gestation) commenced and 37 (77 %) completed at least 80 % of
      the six session group intervention. Significant improvements with moderate to
      large effect sizes were observed for depression as measured on the Centre of
      Epidemiological Studies Depression Scale (CES-D) (p < 0.001), Edinburgh Postnatal
      Depression Scale (EPDS) (p < 0.001), state anxiety (p < 0.001) and maternal
      attachment (p = 0.006). Improvements in posttreatment depression scores on the
      EPDS were maintained at 2 months postpartum. Participants reported that the
      program had met their expectations. Partners (n = 21) who completed evaluation
      forms indicated that their attendance had improved their awareness of their
      partner's mental health issues and resources available to their family and would
      recommend the program to other fathers. These preliminary findings suggest that
      our antenatal group program is an effective and acceptable intervention for a
      clinical sample of women and partners. It is a feasible addition or alternative
      treatment option to perinatal mental health care. Future directions could involve
      more comprehensive randomised controlled trials (RCT) to examine the
      effectiveness of the group intervention. 

PMID- 25074562
TI  - Evaluation of fritless solid-phase extraction coupled on-line with capillary
      electrophoresis-mass spectrometry for the analysis of opioid peptides in
      cerebrospinal fluid.
AB  - Fritless SPE on-line coupled to CE with UV and MS detection (SPE-CE-UV and SPE-CE
      MS) was evaluated for the analysis of opioid peptides. A microcartridge of 150
      MUm id was packed with a C18 sorbent (particle size > 50 MUm), which was retained
      between a short inlet capillary and a separation capillary (50 MUm id). Several
      experimental parameters were optimized by SPE-CE-UV using solutions of dynorphin
      A (DynA), endomorphin 1 (End1), and methionine-enkephaline (Met). A
      microcartridge length of 4 mm was selected, sample was loaded for 10 min at 930
      mbar and the retained peptides were eluted with 67 nL of an acidic hydro-organic
      solution. Using SPE-CE-MS, peak area and migration time repeatabilities for the
      three opioid peptides were 12-27% and 4-5%, respectively. SPE recovery was lower
      for the less hydrophobic DynA (22%) than for End1 (66%) and Met (78%) and
      linearity was satisfactory in all cases between 5 and 60 ng/mL. The LODs varied
      between 0.5 and 1.0 ng/mL which represent an enhancement of two orders of
      magnitude when compared with CE-MS. Cerebrospinal fluid (CSF) samples spiked with
      the opioid peptides were analyzed to demonstrate the applicability to biological
      samples. Peak area and migration time repeatabilities were similar to the
      standard solutions and the opioid peptides could be detected down to 1.0 ng/mL.

PMID- 25074563
TI  - The influence of asthma on face shape: a three-dimensional study.
AB  - Respiratory activity may have an influence on craniofacial development and
      interact with genetic and environmental factors. It has been suggested that
      certain medical conditions such as asthma have an influence on face shape. The
      aim of the study is to investigate whether facial shape is different in
      individuals diagnosed as having asthma compared with controls. Study design
      included observational longitudinal cohort study. Asthma was defined as reported
      wheezing diagnosed at age 7 years and 6 months. The cohort was followed to 15
      years of age as part of the Avon Longitudinal Study of Parents and Children. A
      total of 418 asthmatics and 3010 controls were identified. Three-dimensional
      laser surface facial scans were obtained. Twenty-one reproducible facial
      landmarks (x, y, z co-ordinates) were identified. Average facial shells were
      created for asthmatic and non-asthmatic males and females to explore surface
      differences. The inter-ala distance was 0.4mm wider (95% CI) and mid-face height
      was 0.4mm (95% CI) shorter in asthmatic females when compared with non-asthmatic
      females. No facial differences were detected in male subjects. Small but
      statistically significant differences were detected in mid-face height and inter
      ala width between asthmatic and non-asthmatic females. No differences were
      detected in males. The lack of detection of any facial differences in males may
      be explained by significant facial variation as a result of achieving different
      stages of facial growth due to pubertal changes, which may mask any underlying
      condition effect.

PMID- 25074565
TI  - Effects of stimulation by three-dimensional natural images on prefrontal cortex
      and autonomic nerve activity: a comparison with stimulation using two-dimensional
      images.
AB  - Empirical evidence suggests that three-dimensional (3D) images of nature promote
      physiological relaxation in humans by providing more realistic effects compared
      with two-dimensional (2D) images. However, no studies have evaluated the
      physiological relaxation effects of nature-derived 3D images on prefrontal cortex
      and autonomic nerve activity. The present study aimed to clarify the
      physiological relaxation effects of visual stimulation by 3D flower images on
      prefrontal cortex and autonomic nerve activity. Nineteen male university students
      (22.2 +/- 0.6 years) were presented with 3D and 2D images of the water lily for
      90 s. Prefrontal cortex activity was measured using near-infrared spectroscopy,
      while autonomic nerve activity was measured using heart rate variability (HRV).
      Psychological effects were determined using a modified semantic differential
      method (SD). Compared with visual stimulation by 2D images, that by 3D images
      resulted in a significant decrease in oxyhemoglobin concentration in the right
      prefrontal cortex, lower sympathetic activity as calculated by the ratio of the
      low-frequency to high-frequency HRV component, and a significantly greater
      realistic feeling as evidenced by higher SD ratings. In conclusion, visual
      stimulation by realistic 3D floral images promotes physiological relaxation more
      effectively than the corresponding 2D image. 

PMID- 25074566
TI  - Effective treatment with intravenous immunoglobulins reduces autoreactive T-cell
      response in patients with CIDP.
AB  - OBJECTIVE: To investigate changes in autoreactive T-cell responses against PMP-22
      and P2 antigen as well as a T-cell memory repertoire in patients with chronic
      inflammatory demyelinating polyneuropathy (CIDP) induced by repeated intravenous
      immunoglobulin (IVIg) treatment. METHODS: In an observational trial, we prepared
      cryopreserved human peripheral blood monocytes from blood from 34 patients with
      CIDP (18 treatment naive and 16 maintenance IVIg treatment) and from 14 healthy
      controls (non-immune neuropathy and healthy control). Treatment response was
      defined by clinical evaluation. The autoantigen-specific T-cell response was
      analysed by enzyme linked immunosorbent spot (ELISPOT) assay before IVIg start
      (baseline) and at follow-up. The T-cell memory subsets were analysed by using
      flow cytometric analysis. RESULTS: Myelin-derived P2-specific and PMP-22-specific
      IFN-gamma producers were increased in IVIg responders compared with non
      responders before treatment, which decreased by repeated IVIg infusion cycles.
      Treatment responders but not non-responders showed higher frequencies of CD4 T
      effector memory (TEM) and T central memory frequencies at baseline compared with
      maintenance IVIg treatment patients and controls. In addition, IVIg treatment was
      associated with a significant reduction in CD8 TEM at follow-up. CONCLUSIONS: Our
      data demonstrate that immunomodulatory treatment with IVIgs on a long-term basis
      reduces the autoreactive T-cell response against PMP-22 and P2-antigens, which
      may be influenced by the altered maintenance of CD8 and CD4 effector/memory T
      cell subsets towards a more anti-inflammatory immune status. Elevated PMP-22 and
      P2-specific T-cell responses may serve as predictors for treatment responsiveness
      to IVIgs warranting validation in larger studies.

PMID- 25074567
TI  - Management of endemic Microsporum canis dermatophytosis in an open admission
      shelter: a field study.
AB  - Endemic Microsporum canis dermatophytosis was identified in a large, open
      admission, private, no-kill shelter that admitted >1200 cats per year. Fungal
      culture (FC) screening revealed that 166/210 (79%) and 38/99 (38%) cats in the
      non-public and public area were culture positive, respectively. However, pending
      screening FC results, the 99 cats in the public area were treated with once
      weekly lime sulfur rinses and monitored with once-weekly FC. Cats in the non
      public area were not treated. When FC results were available, cats were separated
      into low-risk (n = 61) and high-risk (n = 38) groups based upon the presence or
      absence of skin lesions. Low-risk cats continued to receive once-weekly topical
      lime sulfur and rapidly achieved culture-negative status. High-risk cats were
      divided into two groups based upon the number of colony-forming units/plate (low
      or high). All 38 cats were treated with twice-weekly lime sulfur and oral
      terbinafine and within 6-7 weeks only 5/38 cats were still FC-positive. These
      cats were moved to a separate room. Dermatophytosis was eradicated within 5
      months; eradication was prolonged owing to reintroduction of disease into the
      remaining room of cats under treatment from three kittens returning from foster
      care. Continued admissions and adoptions were possible by the institution of
      intake procedures that specifically included careful Wood's lamp examination to
      identify high-risk cats and use of a 'clean break strategy'. 

PMID- 25074568
TI  - Patellar ligament rupture in the cat: repair methods and patient outcomes in
      seven cases.
AB  - The medical records of cats receiving surgical treatment for unilateral patellar
      ligament rupture between 1999 and 2012 at 12 referral centres in the UK and
      Ireland were reviewed. Seven cases were identified: six were caused by trauma and
      one was iatrogenic, occurring as a complication following surgical stabilisation
      of a tibial fracture. All cases were treated by sutured anastomosis of the
      ruptured ligament, with six of the repairs protected by a circumpatellar and/or
      transpatellar loop of suture. The stifle was immobilised by transarticular
      external skeletal fixation in three cases. No cases required revision surgery. No
      complications were reported. Final evaluation, performed at a median time of 31
      days, determined five patients to have returned to acceptable or good limb
      function; two cases were lost to follow-up. The data suggest that, in cats, the
      current surgical techniques extrapolated from their canine counterparts for
      repair of a completely or partially ruptured patellar ligament are successfully
      used and result in acceptable limb function. 

PMID- 25074570
TI  - Island colonisation and the evolutionary rates of body size in insular neonate
      snakes.
AB  - Island colonisation by animal populations is often associated with dramatic
      shifts in body size. However, little is known about the rates at which these
      evolutionary shifts occur, under what precise selective pressures and the
      putative role played by adaptive plasticity on driving such changes. Isolation
      time played a significant role in the evolution of body size in island Tiger
      snake populations, where adaptive phenotypic plasticity followed by genetic
      assimilation fine-tuned neonate body and head size (hence swallowing performance)
      to prey size. Here I show that in long isolated islands (>6000 years old) and
      mainland populations, neonate body mass and snout-vent length are tightly
      correlated with the average prey body mass available at each site. Regression
      line equations were used to calculate body size values to match prey size in four
      recently isolated populations of Tiger snakes. Rates of evolution in body mass
      and snout-vent length, calculated for seven island snake populations, were
      significantly correlated with isolation time. Finally, rates of evolution in body
      mass per generation were significantly correlated with levels of plasticity in
      head growth rates. This study shows that body size evolution occurs at a faster
      pace in recently isolated populations and suggests that the level of adaptive
      plasticity for swallowing abilities may correlate with rates of body mass
      evolution. I hypothesise that, in the early stages of colonisation, adaptive
      plasticity and directional selection may combine and generate accelerated
      evolution towards an 'optimal' phenotype. 

PMID- 25074569
TI  - Mining the pig genome to investigate the domestication process.
AB  - Pig domestication began around 9000 YBP in the Fertile Crescent and Far East,
      involving marked morphological and genetic changes that occurred in a relatively
      short window of time. Identifying the alleles that drove the behavioural and
      physiological transformation of wild boars into pigs through artificial selection
      constitutes a formidable challenge that can only be faced from an
      interdisciplinary perspective. Indeed, although basic facts regarding the
      demography of pig domestication and dispersal have been uncovered, the biological
      substrate of these processes remains enigmatic. Considerable hope has been placed
      on new approaches, based on next-generation sequencing, which allow whole-genome
      variation to be analyzed at the population level. In this review, we provide an
      outline of the current knowledge on pig domestication by considering both
      archaeological and genetic data. Moreover, we discuss several potential scenarios
      of genome evolution under the complex mixture of demography and selection forces
      at play during domestication. Finally, we highlight several technical and
      methodological approaches that may represent significant advances in resolving
      the conundrum of livestock domestication.

PMID- 25074571
TI  - Inbreeding interferes with the heat-shock response.
AB  - Inbreeding is typically detrimental to individual fitness, with negative effects
      being often exaggerated in stressful environments. However, the causal mechanisms
      underlying inbreeding depression in general and the often increased
      susceptibility to stress in particular are not well understood. We here test
      whether inbreeding interferes with the heat-shock response, comprising an
      important component of the stress response which may therefore underscore
      sensitivity to stress. To this end we subjected the tropical butterfly Bicyclus
      anynana to a full-factorial design with three temperatures and three levels of
      inbreeding, and measured the expression of heat-shock protein (HSP) 70 via qPCR.
      HSP70 expression increased after exposure to heat as compared with cold or
      control conditions. Most strikingly, inbreeding strongly interfered with the heat
      shock response, with inbred individuals showing a very weak upregulation of HSP70
      only. Our results thus indicate that, in our study organism, interference with
      the heat-shock response may be one mechanism underlying reduced fitness of inbred
      individuals, especially when exposed to stressful conditions. However, these
      indications need to be corroborated using a broader range of different
      temperatures, genes and taxa. 

PMID- 25074572
TI  - Phenotypic divergence of the common toad (Bufo bufo) along an altitudinal
      gradient: evidence for local adaptation.
AB  - Variation in the environment can induce different patterns of genetic and
      phenotypic differentiation among populations. Both neutral processes and
      selection can influence phenotypic differentiation. Altitudinal phenotypic
      variation is of particular interest in disentangling the interplay between
      neutral processes and selection in the dynamics of local adaptation processes but
      remains little explored. We conducted a common garden experiment to study the
      phenotypic divergence in larval life-history traits among nine populations of the
      common toad (Bufo bufo) along an altitudinal gradient in France. We further used
      correlation among population pairwise estimates of quantitative trait (QST) and
      neutral genetic divergence (FST from neutral microsatellite markers), as well as
      altitudinal difference, to estimate the relative role of divergent selection and
      neutral genetic processes in phenotypic divergence. We provided evidence for a
      neutral genetic differentiation resulting from both isolation by distance and
      difference in altitude. We found evidence for phenotypic divergence along the
      altitudinal gradient (faster development, lower growth rate and smaller
      metamorphic size). The correlation between pairwise QSTs-FSTs and altitude
      differences suggested that this phenotypic differentiation was most likely driven
      by altitude-mediated selection rather than by neutral genetic processes.
      Moreover, we found different divergence patterns for larval traits, suggesting
      that different selective agents may act on these traits and/or selection on one
      trait may constrain the evolution on another through genetic correlation. Our
      study highlighted the need to design more integrative studies on the common toad
      to unravel the underlying processes of phenotypic divergence and its selective
      agents in the context of environmental clines. 

PMID- 25074573
TI  - Systematic differences in the response of genetic variation to pedigree and
      genome-based selection methods.
AB  - Genomic selection (GS) is a DNA-based method of selecting for quantitative traits
      in animal and plant breeding, and offers a potentially superior alternative to
      traditional breeding methods that rely on pedigree and phenotype information.
      Using a 60 K SNP chip with markers spaced throughout the entire chicken genome,
      we compared the impact of GS and traditional BLUP (best linear unbiased
      prediction) selection methods applied side-by-side in three different lines of
      egg-laying chickens. Differences were demonstrated between methods, both at the
      level and genomic distribution of allele frequency changes. In all three lines,
      the average allele frequency changes were larger with GS, 0.056 0.064 and 0.066,
      compared with BLUP, 0.044, 0.045 and 0.036 for lines B1, B2 and W1, respectively.
      With BLUP, 35 selected regions (empirical P < 0.05) were identified across the
      three lines. With GS, 70 selected regions were identified. Empirical thresholds
      for local allele frequency changes were determined from gene dropping, and
      differed considerably between GS (0.167-0.198) and BLUP (0.105-0.126). Between
      lines, the genomic regions with large changes in allele frequencies showed
      limited overlap. Our results show that GS applies selection pressure much more
      locally than BLUP, resulting in larger allele frequency changes. With these
      results, novel insights into the nature of selection on quantitative traits have
      been gained and important questions regarding the long-term impact of GS are
      raised. The rapid changes to a part of the genetic architecture, while another
      part may not be selected, at least in the short term, require careful
      consideration, especially when selection occurs before phenotypes are observed.

PMID- 25074574
TI  - Reduced recombination patterns in Robertsonian hybrids between chromosomal races
      of the house mouse: chiasma analyses.
AB  - The recombination suppression models of chromosomal speciation posit that
      chromosomal rearrangements act as partial barriers to gene flow allowing these
      regions to accumulate genetic incompatibilities, thus contributing to the
      divergence of populations. Empirical and theoretical studies exploring the
      requirements of these models have mostly focused on the role of inversions. Here,
      the recombination landscape of heterozygosity for Robertsonian (Rb) fusions is
      investigated in the house mouse. Laboratory-bred F1 males and females between
      highly differentiated races from Tunisia (Rb: 2n=22, Standard, St: 2n=40) were
      produced in which all Rb fusions are present as trivalents in meiosis.
      Recombination patterns were determined by the analysis of chiasmata and compared
      with previous data on the Tunisian parental mice. A comparative analysis was
      performed on wild-caught male mice spanning the hybrid zone between two Italian
      races (2n=40, 2n=22). The results showed that the chiasma characteristics of both
      male and female Tunisian F1 and Italian hybrids clearly differed from those of Rb
      and St mice. Not only was the mean chiasma number (CN) intermediate between those
      of the parental mice in both geographic samples, but the distribution of
      chiasmata along the chromosomal arms of the F1 showed a distinct mosaic pattern.
      In short, the proximal region in the F1 exhibited a reduced CN similar to that
      observed in homozygous Rb, whereas distal regions more closely matched those in
      St mice. These results suggest that Rb rearrangements (homozygous or
      heterozygous) reduce recombination in the proximal regions of the chromosomes
      supporting their potential role in recombination-mediated speciation models.

PMID- 25074576
TI  - Influence of ecological and geological features on rangewide patterns of genetic
      structure in a widespread passerine.
AB  - Geological and ecological features restrict dispersal and gene flow, leading to
      isolated populations. Dispersal barriers can be obvious physical structures in
      the landscape; however microgeographic differences can also lead to genetic
      isolation. Our study examined dispersal barriers at both macro- and micro
      geographical scales in the black-capped chickadee, a resident North American
      songbird. Although birds have high dispersal potential, evidence suggests
      dispersal is restricted by barriers. The chickadee's range encompasses a number
      of physiological features which may impede movement and lead to divergence.
      Analyses of 913 individuals from 34 sampling sites across the entire range using
      11 microsatellite loci revealed as many as 13 genetic clusters. Populations in
      the east were largely panmictic whereas populations in the western portion of the
      range showed significant genetic structure, which often coincided with large
      mountain ranges, such as the Cascade and Rocky Mountains, as well as areas of
      unsuitable habitat. Unlike populations in the central and southern Rockies,
      populations on either side of the northern Rockies were not genetically distinct.
      Furthermore, Northeast Oregon represents a forested island within the Great
      Basin; genetically isolated from all other populations. Substructuring at the
      microgeographical scale was also evident within the Fraser Plateau of central
      British Columbia, and in the southeast Rockies where no obvious physical barriers
      are present, suggesting additional factors may be impeding dispersal and gene
      flow. Dispersal barriers are therefore not restricted to large physical
      structures, although mountain ranges and large water bodies do play a large role
      in structuring populations in this study. 

PMID- 25074577
TI  - Furin mediates brain-derived neurotrophic factor upregulation in cultured rat
      astrocytes exposed to oxygen-glucose deprivation.
AB  - This study investigated the changes in brain-derived neurotrophic factor (BDNF)
      expression and the role of furin in BDNF maturation in reactive astrocytes from
      rats exposed to oxygen-glucose deprivation (OGD). Furin, a proprotein convertase,
      is upregulated and cleaves certain substrates during hypoxia in cancer cells. In
      addition, during hypoxia in the central nervous system, astrocytes become
      reactive and release BDNF to protect neurons. Maturation of BDNF in astrocytes
      requires furin-mediated endoproteolytic processing of the precursor protein pro
      BDNF to BDNF. To expand our knowledge about the role of furin in BDNF maturation
      in astrocytes, these cells were exposed to OGD, and expression of furin and BDNF
      was detected by Western blot analysis. Changes in BDNF expression were observed
      when furin activity was inhibited by furin prosegment. We found that protein
      expression of BDNF and furin was upregulated, and this upregulation correlated
      with OGD stimulation. Furin inhibition reduced BDNF maturation and secretion.
      These results indicate that furin mediates the upregulation of BDNF in reactive
      astrocytes exposed to OGD and that furin may impact the biological effect of
      reactive astrocytes.

PMID- 25074578
TI  - Hourly awakening vs continuous contact lens sensor measurements of 24-hour
      intraocular pressure: effect on sleep macrostructure and intraocular pressure
      rhythm.
AB  - IMPORTANCE: All studies of 24-hour intraocular pressure (IOP) rhythm conducted to
      date have used repeated IOP measurements requiring nocturnal awakenings,
      potentially disturbing sleep macrostructure. OBJECTIVE: To evaluate the effects
      on sleep architecture and IOP rhythm of hourly awakening vs a contact lens sensor
      (CLS) to continuously monitor IOP without awakening. DESIGN, SETTING, AND
      PARTICIPANTS: Cross-sectional study at a referral center of chronobiology among
      12 young healthy volunteers, with a mean (SD) age of 22.3 (2.3) years.
      INTERVENTIONS: Volunteers underwent two 24-hour IOP measurement sessions during a
      2-month period. The eye order and session order were randomized. During one
      session, the IOP of the first eye was continuously monitored using a CLS, and the
      IOP of the fellow eye was measured hourly using a portable noncontact tonometer
      (session with nocturnal hourly awakening). During the other session, the IOP of
      the first eye was continuously monitored using a CLS, and the IOP of the fellow
      eye was not measured (session without nocturnal awakening). Overnight
      polysomnography was performed during the 2 sessions. MAIN OUTCOMES AND MEASURES:
      A nonlinear least squares, dual-harmonic regression analysis was used to model
      the 24-hour IOP rhythm from the CLS data. Comparisons of acrophase, bathyphase,
      amplitude, and the midline estimating statistic of rhythm were used to evaluate
      the effect of hourly awakening on IOP rhythm. To evaluate the effects of hourly
      awakening on sleep architecture, comparisons of sleep structure were used,
      including total sleep period, rapid eye movement, wake after sleep onset,
      absolute and relative total sleep time, and non-rapid eye movement sleep (N1, N2,
      and N3). RESULTS: A 24-hour IOP rhythm was found in all individuals for the
      sessions with and without awakening (P < .05). Hourly awakening for nocturnal IOP
      measurements increased wake after sleep onset (P = .04) but did not seem to
      change total sleep time, total sleep period, sleep efficiency, or slow-wave and
      rapid eye movement sleep stage duration (P > .30). Hourly awakening during
      noncontact tonometer IOP measurements did not seem to alter the mean variables of
      the 24-hour IOP pattern evaluated using CLS, including signal, maximum signal,
      minimum signal, acrophase, and bathyphase (P > .15). CONCLUSION AND RELEVANCE:
      The 24-hour IOP rhythms seem to be unaffected by hourly nocturnal awakening for
      IOP measurements in young healthy individuals.

PMID- 25074579
TI  - Myeloblative therapy with autologous haematopoietic stem cell support as
      consolidation of first remission in acute myeloid leukaemia - very long follow
      up.

PMID- 25074580
TI  - Bias in tree searches and its consequences for measuring group supports.
AB  - When doing a bootstrap analysis with a single tree saved per pseudoreplicate,
      biased search algorithms may influence support values more than actual properties
      of the data set. Two methods commonly used for finding phylogenetic trees consist
      of randomizing the input order of species in multiple addition sequences followed
      by branch swapping, or using random trees as the starting point for branch
      swapping. The randomness inherent to such methods is assumed to eliminate any
      consistent preferences for some trees or unsupported groups of taxa, but both
      methods can be significantly biased. In the case of trees created by sequentially
      adding taxa, a bias may occur even if every addition sequence is equiprobable,
      and if one of the equally optimal positions for each terminal to add to the tree
      is selected equiprobably. In the case of branch swapping, the bias can happen
      even when branch swapping equiprobably selects any of the trees of better score
      in the subtree-pruning-regrafting-neighborhood or tree-bisection-reconnection
      neighborhood. Consequently, when the data set is ambiguous, both random-addition
      sequences and branch swapping from random trees may (i) find some of the optimal
      trees much more frequently than others and (ii) find some groups with a frequency
      that differs from their frequency among all optimal trees. When the data set
      defines a single optimal tree, the groups present in that tree may have a
      different probability of being found by a search, even if supported by equal
      amounts of evidence. This may happen in both parsimony and maximum-likelihood
      analyses, and even in small data sets without incongruence. 

PMID- 25074581
TI  - Spring constant calibration techniques for next-generation fast-scanning atomic
      force microscope cantilevers.
AB  - As a recent technological development, high-speed atomic force microscopy (AFM)
      has provided unprecedented insights into dynamic processes on the nanoscale, and
      is capable of measuring material property variation over short timescales.
      Miniaturized cantilevers developed specifically for high-speed AFM differ greatly
      from standard cantilevers both in size and dynamic properties, and calibration of
      the cantilever spring constant is critical for accurate, quantitative
      measurement. This work investigates specifically, the calibration of these new
      generation cantilevers for the first time. Existing techniques are tested and the
      challenges encountered are reported and the most effective approaches for
      calibrating fast-scanning cantilevers with high accuracy are identified,
      providing a resource for microscopists in this rapidly developing field. Not only
      do these cantilevers offer faster acquisition of images and force data but due to
      their high resonant frequencies (up to 2 MHz) they are also excellent mass
      sensors. Accurate measurement of deposited mass requires accurate calibration of
      the cantilever spring constant, therefore the results of this work will also be
      useful for mass-sensing applications. 

PMID- 25074575
TI  - Exonic versus intronic SNPs: contrasting roles in revealing the population
      genetic differentiation of a widespread bird species.
AB  - Recent years have seen considerable progress in applying single nucleotide
      polymorphisms (SNPs) to population genetics studies. However, relatively few have
      attempted to use them to study the genetic differentiation of wild bird
      populations and none have examined possible differences of exonic and intronic
      SNPs in these studies. Here, using 144 SNPs, we examined population genetic
      differentiation in the saker falcon (Falco cherrug) across Eurasia. The position
      of each SNP was verified using the recently sequenced saker genome with 108 SNPs
      positioned within the introns of 10 fragments and 36 SNPs in the exons of six
      genes, comprising MHC, MC1R and four others. In contrast to intronic SNPs, both
      Bayesian clustering and principal component analyses using exonic SNPs
      consistently revealed two genetic clusters, within which the least admixed
      individuals were found in Europe/central Asia and Qinghai (China), respectively.
      Pairwise D analysis for exonic SNPs showed that the two populations were
      significantly differentiated and between the two clusters the frequencies of five
      SNP markers were inferred to be influenced by selection. Central Eurasian
      populations clustered in as intermediate between the two main groups, consistent
      with their geographic position. But the westernmost populations of central Europe
      showed evidence of demographic isolation. Our work highlights the importance of
      functional exonic SNPs for studying population genetic pattern in a widespread
      avian species.

PMID- 25074582
TI  - The CCCH zinc finger protein gene AtZFP1 improves salt resistance in Arabidopsis
      thaliana.
AB  - The CCCH type zinc finger proteins are a super family involved in many aspects of
      plant growth and development. In this study, we investigated the response of one
      CCCH type zinc finger protein AtZFP1 (At2g25900) to salt stress in Arabidopsis.
      The expression of AtZFP1 was upregulated by salt stress. Compared to transgenic
      strains, the germination rate, emerging rate of cotyledons and root length of
      wild plants were significantly lower under NaCl treatments, while the inhibitory
      effect was significantly severe in T-DNA insertion mutant strains. At germination
      stage, it was mainly osmotic stress when treated with NaCl. Relative to wild
      plants, overexpression strains maintained a higher K(+), K(+)/Na(+), chlorophyll
      and proline content, and lower Na(+) and MDA content. Quantitative real-time PCR
      analysis revealed that the expression of stress related marker genes KIN1, RD29B
      and RD22 increased more significantly in transgenic strains by salt stress.
      Overexpression of AtZFP1 also enhanced oxidative and osmotic stress tolerance
      which was determined by measuring the expression of a set of antioxidant genes,
      osmotic stress genes and ion transport protein genes such as SOS1, AtP5CS1 and
      AtGSTU5. Overall, our results suggest that overexpression of AtZFP1 enhanced salt
      tolerance by maintaining ionic balance and limiting oxidative and osmotic stress.

PMID- 25074583
TI  - Do cognitive and physical fatigue tasks enhance pain, cognitive fatigue, and
      physical fatigue in people with fibromyalgia?
AB  - OBJECTIVE: Fibromyalgia is a condition characterized by chronic widespread muscle
      pain and fatigue. The primary objective of this study was to determine if pain,
      perceived cognitive fatigue, and perceived physical fatigue were enhanced in
      participants with fibromyalgia compared to healthy controls during a cognitive
      fatigue task, a physical fatigue task, and a dual fatigue task. METHODS: In
      total, 24 people with fibromyalgia and 33 healthy controls completed pain,
      fatigue, and function measures. A cognitive fatigue task (Controlled Oral Word
      Association Test) and physical fatigue task (Valpar peg test) were done
      individually and combined for a dual fatigue task. Resting pain, perceived
      cognitive fatigue, and perceived physical fatigue were assessed during each task
      using visual analog scales. Function was assessed with shoulder range of motion
      and grip. RESULTS: People with fibromyalgia had significantly higher increases in
      pain, cognitive fatigue, and physical fatigue when compared to healthy controls
      after completion of a cognitive fatigue task, a physical fatigue task, or a dual
      fatigue task (P < 0.01) with the exception of perceived cognitive fatigue during
      the cognitive fatigue task. People with fibromyalgia performed equivalently on
      measures of physical performance and cognitive performance on the physical and
      cognitive fatigue tasks, respectively. CONCLUSION: These data show that people
      with fibromyalgia show larger increases in pain, perceived cognitive fatigue, and
      perceived physical fatigue to both cognitive and physical fatigue tasks compared
      to healthy controls. The increases in pain and fatigue during cognitive and
      physical fatigue tasks could influence subject participation in daily activities
      and rehabilitation.

PMID- 25074584
TI  - Expression of Nfic during root formation in first mandibular molar of rat.
AB  - The transcription factor Nfic is a key regulator during tooth development. Nfic
      deficient mice exhibit short and abnormal molar roots and severely deformed
      incisors. Dental epithelial cells, known as Hertwig's epithelial root sheath
      (HERS), participate in root formation. However, whether Nfic is involved in HERS
      mesenchyme interaction remains unclear. In this study, the detail temporal and
      spatial expression pattern of Nfic during rat molar development was examined
      using immunohistochemistry and in situ hybridization. Nfic was detected in
      ameloblasts, dental follicle cells (DFCs) and dental papilla cells (DPCs),
      especially the DPCs close to dentin, from postnatal day 5 to day 16. Nfic
      expression in DPCs, DFCs and HERS cells was also examined by western blot and RT
      PCR. Nfic was detected in DPCs and DFCs, but not in HERS cells. Co-culture
      experiment further indicated that Nfic mRNA expression in DPCs was elevated by
      the presence of HERS cells. Our results revealed that Nfic could be a marker gene
      for root odontoblasts differentiation initiation and its expression might be
      regulated through epithelial-mesenchymal interaction. 

PMID- 25074585
TI  - Up-regulation of SKIP relates to retinal ganglion cells apoptosis after optic
      nerve crush in vivo.
AB  - Cell cycle re-entry is one of the key processes in neuronal apoptosis. Previous
      studies have shown that Ski-interacting protein (SKIP) played an important role
      in cell cycle re-entry. However, its expression and function in optic nerve
      injury are still with limited acquaintance. To investigate whether SKIP is
      involved in retinal ganglion cells (RGCs) death, we performed an optic nerve
      crush (ONC) model in adult rats. Western blot analysis revealed that up
      regulation of SKIP was present in retina at 5 days after ONC. Immunofluorescent
      labeling indicated that up-regulated SKIP was found mainly in RGCs. We also
      investigated co-localization of SKIP with active-caspase-3 and TUNEL (apoptotic
      markers) -positive cells in the retina after ONC. In addition, the expression of
      SKIP was increased in parallel with P53 and P21 in retina after ONC. All these
      results suggested that up-regulation of SKIP in the retina was associated with
      RGCs death after ONC. 

PMID- 25074586
TI  - An apple B-box protein, MdCOL11, is involved in UV-B- and temperature-induced
      anthocyanin biosynthesis.
AB  - MAIN CONCLUSION: Our studies showed that an apple B-box protein, MdCOL11, the
      homolog of AtBBX22, is involved in UV-B- and temperature-induced anthocyanin
      biosynthesis in apple peel. Anthocyanin is responsible for the red pigmentation
      in apple peel and a R2R3 MYB gene, MdMYBA/1/10, a homolog of MdMYBA, controls its
      accumulation. Arabidopsis PAP1 is under the control of a series of upstream
      factors involved in light signal transduction and photomorphogenesis, such as
      ELONGATED HYPOCOTYL 5 (HY5) and B-box family (BBX) proteins. In this study, we
      identified and characterized the homolog of Arabidopsis BBX22 in apple,
      designated as MdCOL11. Overexpression of MdCOL11 in Arabidopsis enhanced the
      accumulation of anthocyanin. In apples, MdCOL11 was differentially expressed in
      all tissues, with the highest expression in petals and the lowest expression in
      the xylem. Transcripts of MdCOL11 noticeably accumulated at the ripening stage,
      concomitant with increases in the expressions of anthocyanin biosynthesis-related
      genes. In an in vitro treatment experiment, MdCOL11 was upregulated in an ultra
      violet (UV)-B- and temperature-dependent manner, together with the inductions of
      anthocyanin biosynthesis-related genes and anthocyanin accumulation in apple
      peel. Furthermore, a dual-luciferase assay indicated that (1) MdCOL11 regulated
      the expression of MdMYBA and (2) MdCOL11 was a target of MdHY5. Taken together,
      our results suggest that MdCOL11 is involved in MdHY5-mediated signal
      transduction and regulates anthocyanin accumulation in apple peel, which sheds
      new light on anthocyanin accumulation in apples.

PMID- 25074588
TI  - Pepper mildew resistance locus O interacts with pepper calmodulin and suppresses
      Xanthomonas AvrBsT-triggered cell death and defense responses.
AB  - MAIN CONCLUSION: Pepper CaMLO2 specifically interacts with CaCaM1 and
      translocates cytoplasmic CaCaM1 to the plasma membrane, leading to the
      suppression of Xanthomonas AvrBsT-triggered Ca (2+) influx, hypersensitive cell
      death and defense responses. Pathogen-induced cell death is closely linked with
      disease susceptibility and resistance in plants. Pepper (Capsicum annuum) mildew
      resistance locus O (CaMLO2) and calmodulin (CaCaM1) genes are required for
      disease-associated cell death and hypersensitive cell death, respectively. Here,
      we demonstrate that pathogen-responsive CaMLO2 interacts with CaCaM1 in yeast and
      in planta. Bimolecular fluorescence complementation and co-immunoprecipitation
      analyses confirm a specific interaction between CaMLO2 and CaCaM1 at the plasma
      membrane (PM) in plant cells. Subcellular localization analyses of CaCaM1 fused
      to green fluorescent protein reveals that treatment with Ca(2+) and co-expression
      with CaMLO2 induce translocation of cytosolic CaCaM1 to the PM where CaMLO2 is
      localized. Transient CaMLO2 expression negatively regulates CaCaM1 accumulation
      in Nicotiana benthamiana. Xanthomonas avrBsT-triggered Ca(2+) influx and
      hypersensitive cell death are disrupted by CaCaM1 and/or CaMLO2 expression.
      CaMLO2 silencing in pepper significantly enhances reactive oxygen species burst,
      cell death, and resistance responses to Xanthomonas campestris pv. vesicatoria
      Ds1 and Ds1 (avrBsT), which is accompanied by enhanced induction of CaCaM1, CaPR1
      (PR-1), and CaPO2 (peroxidase). These results suggest that CaMLO2 interacts with
      CaCaM1 and suppresses AvrBsT-triggered cell death and defense responses.

PMID- 25074587
TI  - OsACA6, a P-type 2B Ca(2+) ATPase functions in cadmium stress tolerance in
      tobacco by reducing the oxidative stress load.
AB  - MAIN CONCLUSION: The present study demonstrates the first direct evidence of the
      novel role of OsACA6 in providing Cd (2+) stress tolerance in transgenic tobacco
      by maintaining cellular ion homeostasis and modulating ROS-scavenging pathway.
      Cadmium, a non-essential toxic heavy metal, interferes with the plant growth and
      development. It reaches the leaves through xylem and may become part of the food
      chain, thus causing detrimental effects to human health. Therefore, there is an
      urgent need to develop strategies for engineering plants for Cd(2+) tolerance and
      less accumulation. The members of P-type ATPases family transport metal ions
      including Cd(2+), and thus play important role an ion homeostasis. The present
      study elucidates the role of P-type 2B Ca(2+) ATPase (OsACA6) in Cd(2+) stress
      tolerance. The transcript levels of OsACA6 were up-regulated upon Cd(2+), Zn(2+)
      and Mn(2+) exposure. Transgenic tobacco expressing OsACA6 showed tolerance
      towards Cd(2+) stress as demonstrated by several physiological indices including
      root length, biomass, chlorophyll, malondialdehyde and hydrogen peroxide content.
      The roots of the transgenic lines accumulated more Cd(2+) as compared to shoot.
      Further, confocal laser scanning microscopy showed that Cd(2+) exposure altered
      Ca(2+) uptake in OsACA6 transgenic plants. OsACA6 expression in tobacco also
      protected the transgenic plants from oxidative stress by enhancing the activity
      of enzymatic (SOD, CAT, APX, GR) and non-enzymatic (GSH and AsA) antioxidant
      machinery. Transgenic lines also tolerated Zn(2+) and Mn(2+) stress; however,
      tolerance for these ions was not as significant as observed for Cd(2+) exposure.
      Thus, overexpression of OsACA6 confers Cd(2+) stress tolerance in transgenic
      lines by maintaining cellular ion homeostasis and modulating reactive oxygen
      species (ROS)-scavenging pathway. The results of the present study will help to
      develop strategies for engineering Cd(2+) stress tolerance in economically
      important crop plants.

PMID- 25074589
TI  - Factors associated with low fitness in adolescents--a mixed methods study.
AB  - BACKGROUND: Fitness and physical activity are important for cardiovascular and
      mental health but activity and fitness levels are declining especially in
      adolescents and among girls. This study examines clustering of factors associated
      with low fitness in adolescents in order to best target public health
      interventions for young people. METHODS: 1147 children were assessed for fitness,
      had blood samples, anthropometric measures and all data were linked with routine
      electronic data to examine educational achievement, deprivation and health
      service usage. Factors associated with fitness were examined using logistic
      regression, conditional trees and data mining cluster analysis. Focus groups were
      conducted with children in a deprived school to examine barriers and facilitators
      to activity for children in a deprived community. RESULTS: Unfit adolescents are
      more likely to be deprived, female, have obesity in the family and not achieve in
      education. There were 3 main clusters for risk of future heart disease/diabetes
      (high cholesterol/insulin); children at low risk (not obese, fit, achieving in
      education), children 'visibly at risk' (overweight, unfit, many hospital/GP
      visits) and 'invisibly at risk' (unfit but not overweight, failing in academic
      achievement). Qualitative findings show barriers to physical activity include
      cost, poor access to activity, lack of core physical literacy skills and limited
      family support. CONCLUSIONS: Low fitness in the non-obese child can reveal a
      hidden group who have high risk factors for heart disease and diabetes but may
      not be identified as they are normal weight. In deprived communities low fitness
      is associated with non-achievement in education but in non-deprived communities
      low fitness is associated with female gender. Interventions need to target
      deprived families and schools in deprived areas with community wide campaigns.

PMID- 25074590
TI  - Predictors of failure of conservative treatment among patients with emphysematous
      pyelonephritis.
AB  - BACKGROUND: Emphysematous pyelonephritis (EPN) is a severe necrotizing infection
      of the renal parenchyma and perirenal tissues that is caused by gas-producing
      bacterial pathogens. Percutaneous drainage is now the gold standard of definitive
      management. The aim of this study is to analyze the predictors associated with
      failure of conservative treatment among patients with EPN and offer the
      recommendation of appropriate empirical antibiotic regimen. METHODS: From January
      2001 to December 2013, 44 consecutive patients were diagnosed with EPN. The
      demographic characteristics, clinical presentations, management strategies, and
      final outcomes were analyzed retrospectively. RESULTS: The overall survival rate
      was 88.6% (39/44). Need for emergency hemodialysis, shock on initial
      presentation, altered mental status, severe hypoalbuminemia, inappropriate
      empirical antibiotic treatment and polymicrobial infections were significantly
      more common in the patients who died compared with the survivors. The overall
      failure rate of conservative treatment was 32.6% (14/43). Severe hypoalbuminemia
      (p = 0.003), need for emergency hemodialysis (p = 0.03), and polymicrobial
      infections (p = 0.04) were significantly associated with failure of conservative
      treatment. Severe hypoalbuminemia was independently associated with conservative
      management failure (p = 0.02). Even in the patients treated with percutaneous
      drainage plus effective antibiotics, failure was still associated with severe
      hypoalbuminemia (p = 0.01). According to the in vitro susceptibility data, third
      generation cephalosporins is recommended as the empirical antibiotic regimen.
      CONCLUSIONS: Both appropriate empirical antibiotic and percutaneous drainage were
      essential for patients with EPN. Patients with severe hypoalbuminemia had a
      higher risk of conservative treatment failure, and additional management may be
      required.

PMID- 25074592
TI  - Beta-blockers are the old BLACK.

PMID- 25074591
TI  - Sentinel surveillance of influenza in Burkina Faso: identification of circulating
      strains during 2010-2012.
AB  - BACKGROUND: Although influenza surveillance has recently been improved in some
      sub-Saharan African countries, no information is yet available from Burkina Faso.
      OBJECTIVES: Our study was the first to determine the prevalence of influenza
      viruses circulating in Burkina Faso through a sentinel surveillance system.
      METHODS: We conducted sentinel surveillance with oropharyngeal (OP) swabs
      collected from outpatients (1 month to 83 years) from six sites in Bobo-Dioulasso
      and Ouagadougou, among patients meeting the WHO/CDC case definition for influenza
      like illness (ILI; fever >=38 degrees C, and cough and/or sore throat in the
      absence of other diagnosis) from July 2010 to May 2012. Influenza viruses were
      detected by real-time RT-PCR using CDC primers, probes, and protocols. RESULTS:
      The first three ILI cases were enrolled each day; of 881 outpatients with ILI
      enrolled and sampled, 58 (6.6%) tested positive for influenza viruses (29
      influenza A and 29 influenza B). Among the influenza A viruses, 55.2% (16/29)
      were influenza A (H1N1)pdm09 and 44.8% (13/29) were seasonal A (H3N2). No cases
      of seasonal A/H1N1 were detected. Patients within 0-5 years and 6-14 years were
      the most affected, comprising 41.4% and 22.4% laboratory-confirmed influenza
      cases, respectively. Influenza infections occurred during both the dry, dusty
      Harmattan months from November to March and the rainy season from June to October
      with peaks in January and August. CONCLUSIONS: This surveillance was the first
      confirming the circulation of influenza A (H1N1)pdm09, A/H3N2, and influenza B
      viruses in humans in Burkina Faso.

PMID- 25074593
TI  - [Expanding the use of volatile anesthetic agents beyond the operating room].

PMID- 25074594
TI  - Role of diffusion-weighted magnetic resonance imaging as an imaging biomarker of
      urothelial carcinoma.
AB  - Diffusion-weighted magnetic resonance imaging is a type of functional imaging
      that is increasingly being applied in the management of upper tract urothelial
      carcinoma and bladder cancer. The image contrast is derived from differences in
      the Brownian motion of water molecules in tissues. The homogenous high signal
      intensity of upper tract urothelial carcinoma and bladder cancer on diffusion
      weighted magnetic resonance imaging provides helpful diagnostic information for
      the presence of cancerous lesions in a non-invasive manner. Recently, growing
      evidence has emerged showing that diffusion-weighted magnetic resonance imaging
      can serve as an imaging biomarker for characterizing cancer pathophysiology,
      because the signal reflects biophysical information about the tissues.
      Quantitative analysis by evaluating the apparent diffusion coefficient values
      potentially reflects the histological grade and the biological aggressiveness of
      urothelial carcinoma. The apparent diffusion coefficient value could be a
      biomarker predicting the clinical course of upper tract urothelial carcinoma and
      bladder cancer. In addition, in chemoradiotherapy-based bladder-sparing
      approaches against muscle-invasive bladder cancer, the role of diffusion-weighted
      magnetic resonance imaging for predicting the chemoradiosensitivity and for
      monitoring therapeutic response has been shown. Diffusion-weighted magnetic
      resonance imaging is expected to improve the diagnostic accuracy, and this
      qualitative information might allow individualized treatment strategies for
      patients with urothelial carcinoma. 

PMID- 25074595
TI  - Department of Defense participation in the Department of Veterans Affairs
      Airborne Hazards and Open Burn Pit Registry: process, guidance to providers, and
      communication.

PMID- 25074597
TI  - Mosquito biosurveillance on Kyushu Island, Japan, with emphasis on Anopheles
      Hyrcanus Group and related species (Diptera: culicidae).
AB  - This report includes the distribution records of the Anopheles (Anopheles)
      Hyrcanus Group and associated species in Kyushu Island, Japan, based on our field
      collections from various localities of 4 prefectures (Fukuoka, Kumamoto,
      Nagasaki, Saga), primarily from 2002-2013. The status of common and potential
      mosquito vectors, particularly Anopheles species, in Japan are noted. 

PMID- 25074596
TI  - The growing challenges of vector-borne diseases to regionally-aligned forces.
AB  - The long-term strategic focus of US foreign policy has pivoted to the Pacific,
      but tensions in the Middle East require constant attention in the present. As our
      current role in Afghanistan diminishes, we must seize the opportunity to refocus
      on the new priority of regionally-aligned forces. The short-term reality requires
      first reestablishing core warfighting competencies of a smaller Army and then
      building the capacity of forces focused on regional alignment. The continuing
      threat of vector-borne and other infectious diseases will present growing
      challenges to US forces focused on regional alignment and engagement. Greater
      understanding of these threats, host nation vulnerabilities and capabilities, and
      the regional presence of international and nongovernmental organizations will
      enable US forces to respond and engage more effectively and appropriately to
      accomplish assigned missions and future contingencies. Effective vector
      surveillance and control has a longstanding and proven record of preventing,
      reducing, and eliminating vector-borne diseases and must remain a focus of
      regionally-aligned forces. Operational readiness of armed forces continues to
      rely heavily on vector surveillance and control, and on personal protection
      strategies. Regionally-aligned forces must also work closely with the US
      Department of State and US Agency for International Development, international
      governments, governmental and nongovernmental organizations, and private
      organizations operating in the region and know how to effectively interact with
      these diverse organizations. In addition, a working knowledge of a host country's
      public health policy, capabilities and economic realities will be essential.
      Teamwork with previously unfamiliar groups and organizations will be an essential
      component of working in regional environments and can present unfamiliar tasks
      for traditionally-trained military units. 

PMID- 25074598
TI  - High-throughput vector-borne disease environmental surveillance by polymerase
      chain reaction according to international accreditation requirements.
AB  - Although vector-borne diseases are specific to the region of the host, there is a
      necessity for surveillance or reference laboratories to perform standardized,
      high-throughput testing capable of meeting the needs of a changing military
      environment and response efforts. The development of standardized, high
      throughput, semiquantitative real-time and reverse transcription real-time
      polymerase chain reaction (PCR) methods allows for the timely dissemination of
      data to interested parties while providing a platform in which long-term sample
      storage is possible for the testing of new pathogens of interest using a
      historical perspective. PCR testing allows for the analysis of multiple pathogens
      from the same sample, thus reducing the workload of entomologists in the field
      and increasing the ability to determine if a pathogen has spread beyond
      traditionally defined locations. US Army Public Health Command Region-Europe
      (USAPHCR-Europe) Laboratory Sciences (LS) has standardized tests for 9 pathogens
      at multiple life stages. All tests are currently under international
      accreditation standards. Using these PCR methods and laboratory model, which have
      universal Department of Defense application, the USAPHCR-Europe LS will generate
      quality data that is scientifically sound and legally defensible to support force
      health protection for the US military in both deployed and garrison environments.

PMID- 25074599
TI  - Evaluation of a rapid immunodiagnostic rabies field surveillance test on samples
      collected from military operations in Africa, Europe, and the Middle East.
AB  - The Anigen Rapid Rabies Antigen Test Kit (Bionote, Inc, Hwaseong, Korea) was
      evaluated using 80 clinical samples collected by US military veterinary units.
      Samples for the study were obtained from brain specimens of domestic and wildlife
      animals that were submitted to the US Army Public Health Command's Veterinary
      Laboratory Europe in Landstuhl, Germany, for rabies testing with the direct
      fluorescent antibody test. The rapid immunodiagnostic test was able to detect
      rabies virus antigen in clinical samples of brain tissue. The rapid
      immunodiagnostic test had an overall sensitivity of 96.9% and specificity of 100%
      when compared to the direct fluorescent antibody test. The rapid immunodiagnostic
      test for rabies virus antigen detection is a straightforward test that can be run
      under field conditions and without a microscope or electricity, and yield results
      in 5 to 10 minutes. This rapid immunodiagnostic test is a quick, inexpensive, and
      easy to use surveillance tool that can identify rabies positive animals and help
      focus targeted control measures with the goal of reducing the rabies burden. 

PMID- 25074600
TI  - Trends in rates of chronic obstructive respiratory conditions among US military
      personnel, 2001-2013.
AB  - BACKGROUND: The US military has been continuously engaged in combat operations
      since 2001. Assessing trends in respiratory health diagnoses during this time of
      prolonged military conflict can provide insight into associated changes in the
      burden of pulmonary conditions in the US military population. PURPOSE: To
      estimate and evaluate trends in rates of chronic obstructive pulmonary diseases
      in the active duty US military population from 2001 through 2013. METHODS: A
      retrospective analysis of ambulatory medical encounter diagnosis data
      corresponding to a study base of over 18 million personnel-years was performed to
      estimate average rates and evaluate temporal trends in rates of chronic
      obstructive lung conditions. Differences in rates and the time trends of those
      rates were evaluated by branch of military service, military occupation, and
      military rank. RESULTS: During the 13-year period, we observed 482,670 encounters
      for chronic obstructive pulmonary disease and allied conditions (ICD-9 490-496)
      among active duty military personnel. Over half (57%) of the medical encounters
      in this category were for a diagnosis of bronchitis, not specified as acute or
      chronic. There was a statistically significant 17.2% average increase in the
      annual rates of this nonspecific bronchitis diagnosis from 2001-2009 (95% CI:
      13.5% to 21.1%), followed by a 23.6% annual decline in the rates from 2009
      through 2013 (95% CI: 8.6% to 36.2%). Statistically significant declines were
      observed in the rates of chronic bronchitis over time (annual percentage decline:
      3.1%; 95% CI: 0.5% to 6.6%) and asthma (annual percentage decline: 5.9%; 95% CI:
      2.5% to 9.2%). A 1.6% annual increase in the rate of emphysema and a 0.1%
      increase in the rate of chronic airways obstruction (not elsewhere classified)
      over the study period were not statistically significant (P>.05). The magnitude
      of the estimated rates of these chronic obstructive lung conditions, and, to a
      lesser extent, the temporal trends in these rates, were sensitive to the
      requirement that there be persistence of the diagnosis evidenced in the medical
      record in order qualify as an incident case. CONCLUSIONS: We observed decreases
      in the rates of asthma and chronic bronchitis over the 13-year study period. The
      increase, and then decrease, over time in rates of bronchitis that has not been
      specified as acute or chronic drives the overall trends in chronic respiratory
      disease trends.

PMID- 25074601
TI  - Coinfection of Mycoplasma pneumonia with chronic Q fever in a nurse deployed to
      Operation Iraqi Freedom: a case study.

PMID- 25074602
TI  - Over the ear Tactical Communication and Protection System use by a light infantry
      (airborne) brigade in Afghanistan.

PMID- 25074603
TI  - Health hazard assessment and the toxicity clearance process.

PMID- 25074604
TI  - Chemical and biological warfare: teaching the forbidden at a state university.

PMID- 25074605
TI  - Using the Army Medical Cost Avoidance Model to prioritize preventive medicine
      initiatives.
AB  - The MCAM's ICD-9 Analysis Tool provides preventive medicine program developers
      with a powerful tool to demonstrate ROI. Previously disjointed cost components
      have been brought together in the MCAM to calculate the total medical cost
      avoided. Users are required to make 4 data entries. In response, the user
      receives the highly coveted medical cost avoidance that should be realized. The
      SPHMP example demonstrates how simple it is to use the MCAM to determine the
      expected ROI.

PMID- 25074606
TI  - The Public Health Specialist Program at the Medical Education and Training
      Campus.

PMID- 25074607
TI  - Managing public health in the Army through a standard community health promotion
      council model.
AB  - CONTEXT: Public health processes in the US Army remain uncoordinated due to
      competing lines of command, funding streams and multiple subject matter experts
      in overlapping public health concerns. The US Army Public Health Command (USAPHC)
      has identified a standard model for community health promotion councils (CHPCs)
      as an effective framework for synchronizing and integrating these overlapping
      systems to ensure a coordinated approach to managing the public health process.
      OBJECTIVE: The purpose of this study is to test a foundational assumption of the
      CHPC effectiveness theory: the 3 features of a standard CHPC model - a CHPC
      chaired by a strong leader, ie, the senior commander; a full time health
      promotion team dedicated to the process; and centralized management through the
      USAPHC - will lead to high quality health promotion councils capable of providing
      a coordinated approach to addressing public health on Army installations. DESIGN:
      The study employed 2 evaluation questions: (1) Do CHPCs with centralized
      management through the USAPHC, alignment with the senior commander, and a health
      promotion operations team adhere more closely to the evidence-based CHPC program
      framework than CHPCs without these 3 features? (2) Do members of standard CHPCs
      report that participation in the CHPC leads to a well-coordinated approach to
      public health at the installation? CONCLUSIONS: The results revealed that both
      time (F(5,76)=25.02, P<.0001) and the 3 critical features of the standard CHPC
      model (F(1,76)=28.40, P<.0001) independently predicted program adherence.
      Evaluation evidence supports the USAPHC's approach to CHPC implementation as part
      of public health management on Army installations. Preliminary evidence suggests
      that the standard CHPC model may lead to a more coordinated approach to public
      health and may assure that CHPCs follow an evidence-informed design. This is
      consistent with past research demonstrating that community coalitions and public
      health systems that have strong leadership; dedicated staff time and expertise;
      influence over policy, governance and oversight; and formalized rules and
      regulations function more effectively than those without. It also demonstrates
      the feasibility of implementing an evidence-informed approach to community
      coalitions in an Army environment.

PMID- 25074608
TI  - Performance excellence: using Lean Six Sigma tools to improve the US Army
      behavioral health surveillance process, boost team morale, and maximize value to
      customers and stakeholders.
AB  - Lean Six Sigma (LSS) is a process improvement, problem-solving methodology used
      in business and manufacturing to improve the speed, quality, and cost of
      products. LSS can also be used to improve knowledge-based products integral to
      public health surveillance. An LSS project by the Behavioral Social Health
      Outcomes Program of the Army Institute of Public Health reduced the number of
      labor hours spent producing the routine surveillance of suicidal behavior
      publication. At baseline, the total number of labor hours was 448; after project
      completion, total labor hours were 199. Based on customer feedback, publication
      production was reduced from quarterly to annually. Process improvements enhanced
      group morale and established best practices in the form of standard operating
      procedures and business rules to ensure solutions are sustained. LSS project
      participation also fostered a change in the conceptualization of tasks and
      projects. These results demonstrate that LSS can be used to inform the public
      health process and should be considered a viable method of improving knowledge
      based products and processes. 

PMID- 25074610
TI  - Molecular pathways: IL11 as a tumor-promoting cytokine-translational implications
      for cancers.
AB  - Emerging evidence suggests that cytokines produced by inflammatory cells act as
      rheostats to link the degree of wounding and local inflammation to epithelial
      cell survival, proliferation, and metabolism that collectively underpin the
      repair response. Among these cytokines, the GP130 family, which encompasses,
      among others, IL6 and IL11, plays a major role in orchestrating these complex
      processes through the activation of the latent signal transducer and activator of
      transcription 3 (STAT3) in the epithelium. However, many of the molecular
      mechanisms that govern and ensure effective epithelial wound healing and
      regeneration renewal also promote tumorigenesis and the progression of
      established cancers. Accordingly, GP130 cytokines endow the inflammatory tumor
      microenvironment with a capacity to promote "cancer hallmark capabilities" of the
      malignant epithelium, while simultaneously suppressing the antitumor response of
      innate and adaptive immune cells. Here, we review some recent insights derived
      from genetic and therapeutic inhibition of the IL6/IL11-GP130-STAT3 signaling
      cascade in the context of preclinical mouse models of cancer, which are likely to
      have implications to other solid malignancies.

PMID- 25074609
TI  - Molecular pathways: not a simple tube--the many functions of blood vessels.
AB  - Although the ability of blood vessels to carry fluid and cells through neoplastic
      tissue is clearly important, other functions of vascular elements that drive
      tumor growth and progression are increasingly being recognized. Vessels can
      provide physical support and help regulate the stromal microenvironment within
      tumors, form niches for tumor-associated stem cells, serve as avenues for local
      tumor spread, and promote relative immune privilege. Understanding the molecular
      drivers of these phenotypes will be critical if we are to therapeutically target
      their protumorigenic effects. The potential for neoplastic cells to
      transdifferentiate into vascular and perivascular elements also needs to be
      better understood, as it has the potential to complicate such therapies. In this
      review, we provide a brief overview of these less conventional vascular functions
      in tumors.

PMID- 25074611
TI  - Aquaporin-4 antibody testing: direct comparison of M1-AQP4-DNA-transfected cells
      with leaky scanning versus M23-AQP4-DNA-transfected cells as antigenic substrate.
AB  - BACKGROUND: Neuromyelitis optica (NMO, Devic syndrome) is associated with
      antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab) in the majority of cases. NMO
      IgG/AQP4-Ab seropositivity in patients with NMO and its spectrum disorders has
      important differential diagnostic, prognostic and therapeutic implications. So
      called cell-based assays (CBA) are thought to provide the best AQP4-Ab detection
      rates. OBJECTIVE: To compare directly the AQP4-IgG detection rates of the
      currently most widely used commercial CBA, which employs cells transfected with a
      full-length (M1)-human AQP4 DNA in a fashion that allows leaky scanning (LS) and
      thus expression of M23-AQP4 in addition to M1-AQP, to that of a newly developed
      CBA from the same manufacturer employing cells transfected with human M23-AQP4
      DNA. METHODS: Results from 368 serum samples that had been referred for routine
      AQP4-IgG determination and had been tested in parallel in the two assays were
      compared. RESULTS: Seventy-seven out of 368 samples (20.9%) were positive for NMO
      IgG/AQP4-Ab in at least one assay. Of these, 73 (94.8%) were positive in both
      assays. A single sample (1.3%) was exclusively positive in the novel assay; three
      samples (3.9%) were unequivocally positive only in the 'classic' assay due to
      high background intensity in the novel assay. Both median fluorescence intensity
      and background intensity were higher in the new assay. CONCLUSIONS: This large
      study did not reveal significant differences in AQP4-IgG detection rates between
      the 'classic' CBA and a new M23-DNA-based CBA. Importantly, our results largely
      re-affirm the validity of previous studies that had used the 'classic' AQP4-CBA
      to establish NMO-IgG/AQP4-Ab seropositivity rates in NMO and in a variety of NMO
      spectrum disorders.

PMID- 25074612
TI  - Aneurysmal dilatation associated with arteriovenous fistula in a transplanted
      kidney after renal biopsies.
AB  - AVF is a known complication of renal biopsy in both native and transplanted
      kidneys. A 20-yr-old woman with bilateral hypoplastic kidneys due to branchio-oto
      renal syndrome had received living-donor renal transplantation from her father at
      the age of 11. She had undergone allograft renal biopsies six times and all
      puncture sites were at the lower pole of her kidney from the first to the fifth
      biopsy. AVF with aneurysmal dilation (30 mm) had developed at the puncture site
      after the fifth biopsy. TAE was successfully performed with 11 platinum coils in
      the branch of the renal artery feeding the aneurysm. According to a review of the
      literature, the incidence of AVF is higher in transplanted kidneys than in native
      kidneys (7.5% vs. 2.1%) because transplanted kidneys, as single kidneys, are
      likely to be punctured repeatedly at the same site. When renal biopsy of a
      transplanted kidney is performed, previous biopsy puncture sites should be
      considered and the biopsy should be performed at a different site, if possible,
      to prevent the development of AVF. 

PMID- 25074613
TI  - Genetic ablation of metadherin inhibits autochthonous prostate cancer progression
      and metastasis.
AB  - Metadherin (MTDH) overexpression in diverse cancer types has been linked to poor
      clinical outcomes, but definitive genetic proof of its contributions to cancer
      remains incomplete. In particular, the degree to which MTDH may contribute to
      malignant progression in vivo is lacking. Here, we report that MTDH is amplified
      frequently in human prostate cancers where its expression levels are tightly
      correlated with prostate cancer progression and poor disease-free survival.
      Furthermore, we show that genetic ablation of MTDH in the transgenic
      adenomcarcinoma of mouse prostate (TRAMP) transgenic mouse model of prostate
      cancer blocks malignant progression without causing defects in the normal
      development of the prostate. Germline deletion of Mtdh in TRAMP mice prolonged
      tumor latency, reduced tumor burden, arrested progression of prostate cancer at
      well-differentiated stages, and inhibited systemic metastasis to distant organs,
      thereby decreasing cancer-related mortality ~10-fold. Consistent with these
      findings, direct silencing of Mtdh in prostate cancer cells decreased
      proliferation in vitro and tumor growth in vivo, supporting an epithelial cell
      intrinsic role of MTDH in prostate cancer. Together, our findings establish a
      pivotal role for MTDH in prostate cancer progression and metastasis and define
      MTDH as a therapeutic target in this setting. Cancer Res; 74(18); 5336-47.
      (c)2014 AACR. 

PMID- 25074614
TI  - TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical
      outcomes in non-small cell lung cancer.
AB  - Toll-like receptors (TLR) recognize pathogen molecules and danger-associated
      signals that stimulate inflammatory processes. TLRs have been studied mainly in
      antigen-presenting cells, where they exert important immune regulatory functions,
      but they are also expressed by epithelial tumor cells, where they have been
      implicated in tumor progression. In this study, we demonstrate that the injection
      of TLR7 agonist in NOD/SCID mice, in C57BL/6 wild-type, and TLR7-deficient mice
      grafted with lung adenocarcinoma tumor cells leads to increased tumor progression
      and chemotherapeutic resistance. In patients with non-small cell lung cancer,
      expression analyses revealed that high TLR7 expression was strongly associated
      with resistance to neoadjuvant chemotherapy and poor clinical outcomes. Our
      findings delineate a crucial role for TLR7 in lung cancer physiopathology. Cancer
      Res; 74(18); 5008-18. (c)2014 AACR. 

PMID- 25074615
TI  - Harnessing the intestinal microbiome for optimal therapeutic immunomodulation.
AB  - Distinct cytotoxic agents currently used in the oncological armamentarium mediate
      their clinical benefit by influencing, directly or indirectly, the immune system
      in such a way that innate and adaptive immunity contributes to the tumoricidal
      activity. Now, we bring up evidence that both arms of anticancer immunity can be
      triggered through the intervention of the intestinal microbiota. Alkylating
      agents, such as cyclophosphamide, set up the stage for enhanced permeability of
      the small intestine, facilitating the translocation of selected arrays of Gram
      positive bacteria against which the host mounts effector pTh17 cells and memory
      Th1 responses. In addition, gut commensals, through lipopolysaccharide and other
      bacterial components, switch the tumor microenvironment, in particular the redox
      equilibrium and the TNF production of intratumoral myeloid cells during therapies
      with platinum salts or intratumoral TLR9 agonists combined with systemic anti
      IL10R Ab respectively. Consequently, antibiotics can compromise the efficacy of
      certain chemotherapeutic or immunomodulatory regimens.

PMID- 25074616
TI  - Immunogenetic studies of chronic lymphocytic leukemia: revelations and
      speculations about ontogeny and clinical evolution.
AB  - Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins
      (BcR IG) has proved instrumental in dissecting chronic lymphocytic leukemia (CLL)
      pathogenesis. Initially, it was the finding that the level of somatic
      hypermutations in rearranged IG heavy-chain genes could define two CLL subtypes
      associated with a different clinical course that drew attention. As the years
      ensued, this not only continued to hold strong, but also revealed an
      unprecedented BcR restriction (aptly coined as "stereotypy"), thus cementing the
      idea that antigenic elements select the leukemic clones. With all this in mind,
      in the present review, we focus on the CLL BcR IG, a molecule that clearly lies
      at the heart of disease pathogenesis, and attempt to distil from past and
      emerging biologic knowledge the most relevant aspects in the context of the
      immunogenetics of CLL, while at the same time provoking questions that remain
      unanswered. We juxtapose CLL with mutated BcR IGs against CLL with unmutated BcR
      IGs due to their striking clinicobiologic differences; however, when considering
      ontogeny, common derivation of the two mutational subtypes cannot be excluded.
      The issue of stereotypy is intertwined throughout and we also raise the subject
      of isotype-switched CLL, which, despite its rarity, contributes intriguing
      ontogenetic hints.

PMID- 25074617
TI  - Characterization of the role of adult neurogenesis in touch-screen discrimination
      learning.
AB  - Recent theories posit that adult neurogenesis supports dentate gyrus pattern
      separation and hence is necessary for some types of discrimination learning.
      Using an inducible transgenic mouse model, we investigated the contribution of
      adult-born neurons to spatial and nonspatial touch-screen discriminations of
      varying levels of difficulty. Arresting neurogenesis caused a modest but
      statistically significant impairment in a position discrimination task. However,
      the effect was present only on trials after a learned discrimination was
      reversed, suggesting that neurogenesis supports cognitive flexibility rather than
      spatial discrimination per se. The deficit was present 4-10 weeks after the
      arrest of neurogenesis but not immediately after, consistent with previous
      evidence that the behavioral effects of arresting neurogenesis arise because of
      the depletion of adult-born neurons at least 1 month old. The arrest of
      neurogenesis failed to affect a nonspatial brightness discrimination task that
      was equal in difficulty to the spatial task. The data suggest that adult
      neurogenesis is not strictly necessary for spatial or perceptual discrimination
      learning and instead implicate adult neurogenesis in factors related to reversal
      learning, such as cognitive flexibility or proactive interference.

PMID- 25074618
TI  - Risk and predictors for early radiation pneumonitis in patients with stage III
      non-small cell lung cancer treated with concurrent or sequential
      chemoradiotherapy.
AB  - BACKGROUND: The rate of radiation pneumonitis (RP) for patients receiving
      chemoradiotherapy has been various across studies. Whether it is related to
      different chemotherapy schedules used in combination with radiation therapy were
      evaluated in this study. New factors associated with RP were also investigated.
      METHODS AND MATERIALS: A total of 369 consecutive patients with Stage III non
      small cell lung cancer treated with chemoradiotherapy were followed after
      radiotherapy (RT). Among them 262 patients received concurrent chemoradiotherapy
      followed by consolidation chemotherapy and 107 patients received only sequential
      chemotherapy after RT. RP was graded according to Common Terminology Criteria for
      Adverse Events version 4.0. RESULTS: The rate of grade >= 2 were 39.7%, 31% and
      33.6% in the concurrent DP (docetaxel/cisplatin), concurrent NP
      (vinorelbine/cisplatin) and sequential group, and grade >= 3 RP were 18.4%, 9.5%,
      and 11.2% respectively. The rate of grade >= 3 RP was significantly higher in
      concurrent DP group than that in concurrent NP group (p = 0.04). RP occurred
      earlier in concurrent DP group than that in the other two groups. There were no
      significant differences in response rate among the three groups. In the
      multivariate analysis, age (OR = 1.99, p = 0.038 and OR = 8.90, p < 0.001),
      chemotherapy schedule (OR = 1.45, p = 0.041 and OR = 1.98, p = 0.013), mean lung
      dose(OR = 1.42, p < 0.001 and OR = 1.64, p < 0.001), and planning target
      volume(OR = 1.004, p = 0.001 and OR = 1.005, p = 0.021) were predictors for both
      grade >= 2 and grade >= 3 RP. Response to treatment was a new predictor for grade
      >= 3 RP only (OR = 4.39, p = 0.034). CONCLUSIONS: Response to treatment was found
      to be a new predictor for grade >= 3 RP. Compared to concurrent NP schedule,
      concurrent DP schedule achieved similar response to treatment but resulted in a
      higher risk of grade >= 3 RP.

PMID- 25074619
TI  - Supraglottic airway devices vs tracheal intubation in children: a quantitative
      meta-analysis of respiratory complications.
AB  - BACKGROUND: Rate of perioperative respiratory complications between tracheal
      intubation (TI) and laryngeal mask airway remains unclear during pediatric
      anesthesia. OBJECTIVES: The aim of the present meta-analysis was to compare the
      perioperative respiratory complications between laryngeal mask airway and TI.
      METHODS: A meta-analysis of available controlled studies comparing laryngeal mask
      airway to TI was conducted. Studies including patients with airway infection were
      excluded. Data from each trial were combined to calculate the pooled odds ratios
      (OR) or mean difference (MD) and 95% confidence intervals. RESULTS: The meta
      analysis was performed on 19 studies. In 12 studies, patients were given muscle
      relaxation, and in 16 studies, ventilation was controlled. During recovery from
      anesthesia, the incidence of desaturation (OR = 0.34 [0.19-0.62]), laryngospasm
      (OR = 0.34 [0.2-0.6]), cough (OR = 0.18 [0.11-0.27]), and breath holding (0.19
      [0.05-0.68]) was lower when laryngeal mask airway was used to secure the airway.
      Postoperative incidences of sore throat (OR = 0.87 [0.53-1.44]), bronchospasm (OR
      = 0.56 [0.25-1.25]), aspiration (1.33 [0.46-3.91]) and blood staining on the
      device (OR = 0.62 [0.21-1.82]) did not differ between laryngeal mask airway and
      TI. Results were homogenous across the studies, with the exceptions of blood
      staining on the device. CONCLUSIONS: This meta-analysis found that the use of
      laryngeal mask airway in pediatric anesthesia results in a decrease in a number
      of common postanesthetic complications. It is therefore a valuable device for the
      management of the pediatric airway.

PMID- 25074621
TI  - Flexible ureteroscopy with holmium laser lithotripsy: a new choice for intrarenal
      stone patients.
AB  - OBJECTIVE: To evaluate the efficiency and safety of flexible ureteroscopy (FURS)
      and holmium lithotripsy for intrarenal stones and to stratify the efficiency and
      safety by stone burdens of <=20, 20-40, and >=40 mm. METHODS: Five hundred eighty
      two patients with intrarenal stones were treated with FURS and holmium
      lithotripsy at a single department from August 2008 to October 2013. Stone size
      was evaluated by calculating the cumulative stone diameter of all intrarenal
      stones, and stone-free status was defined as the absence of any stone or stone
      fragment <1 mm in the kidney. RESULTS: Data analysis revealed a mean stone burden
      of 21.8 +/- 7.6 mm. The overall primary stone-free rate (SFR) was 65.3%, which
      increased to 89.0% 6 months after the first surgery. Complications developed in
      6.7% of patients. A significant difference was found between lower-calyx stones
      and other stones (p < 0.001; p = 0.006), while noncalcium stones had a much
      higher SFR than calcium stones (p < 0.001; p = 0.04). CONCLUSION: Our study
      showed that the overall renal SFR with the use of FURS and holmium lithotripsy
      was satisfactory, with a relatively low complication rate. We believe that FURS
      with holmium lithotripsy could be a valuable choice for patients with renal
      stones, especially for patients with a cumulative stone burden <=40 mm.

PMID- 25074622
TI  - Young children's agent-neutral representations of action roles.
AB  - Recent developmental research has shown that young children coordinate
      complementary action roles with others. But what do they understand about the
      logical structure of such roles? Do they have an agent-neutral conception of
      complementary action roles, grasping that such roles can be variably filled by
      any two agents or even by one agent over time? Accordingly, can they make use of
      such representations for planning both their own and others' actions? To address
      these questions, 3- and 4-year-olds were introduced to an activity comprising two
      action roles, A and B, by seeing either two agents performing A and B
      collaboratively or one agent performing A and B individually. Children's flexible
      inferences from these demonstrations were then tested by asking them later on to
      plan ahead for the fulfillment of one of the roles either by themselves or by
      someone else. The 4-year-olds competently drew inferences in all directions, from
      past individual and collaborative demonstrations, when planning how they or
      someone else would need to fulfill the roles in the future. The 3-year-olds, in
      contrast, showed more restricted competence; they were capable of such inferences
      only when planning in the immediate present. Taken together, these results
      suggest that children form and use agent-neutral representations of action roles
      by 3 years of age and flexibly use such representations for episodic memory and
      future deliberation in planning their own and others' actions by 4 years of age.
      The findings are discussed in the broader context of the development of
      understanding self-other equivalence and agent-neutral frames of references.

PMID- 25074623
TI  - Chinese patent medicines for the treatment of the common cold: a systematic
      review of randomized clinical trials.
AB  - BACKGROUND: Many Chinese patent medicines (CPMs) have been authorized by the
      Chinese State of Food and Drug Administration for the treatment of the common
      cold. A number of clinical trials have been conducted and published. However,
      there is no systematic review or meta-analysis on their efficacy and safety for
      the common cold to justify their clinical use. METHODS: We searched CENTRAL,
      MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database,
      China Dissertation Database, and online clinical trial registry websites for
      published and unpublished randomized clinical trials (RCTs) of CPMs for the
      common cold till 31 March 2013. Revman 5.2 software was used for data analysis
      with effect estimate presented as relative risk (RR) and mean difference (MD)
      with a 95% confidence interval (CI). RESULTS: A total of five RCTs were
      identified. All of the RCTs were of high risk of bias with flawed study design
      and poor methodological quality. All RCTs included children aged between 6 months
      to 14 years. Results of individual trials showed that Shuanghuanglian oral liquid
      (RR 4.00; 95% CI: 2.26 to 7.08), and Xiaoer Resuqing oral liquid (RR 1.43; 95%
      CI: 1.15 to 1.77) had higher cure rates compared with antivirus drugs. Most of
      the trials did not report adverse events, and the safety of CPMs was still
      uncertain. CONCLUSIONS: Some CPMs showed a potential positive effect for the
      common cold on cure rate. However, due to the poor methodology quality and the
      defects in the clinical design of the included RCTs, such as the lack of placebo
      controlled trials, the inappropriate comparison intervention and outcome
      measurement, the confirmative conclusions on the beneficial effect of CPMs for
      the common cold could not be drawn.

PMID- 25074625
TI  - Full-thickness skin with mature hair follicles generated from tissue culture
      expanded human cells.
AB  - The goal of regenerative medicine is to reconstruct fully functional organs from
      tissue culture expanded human cells. In this study, we report a method for human
      reconstructed skin (hRSK) when starting with human cells. We implanted tissue
      culture expanded human epidermal and dermal cells into an excision wound on the
      back of immunodeficient mice. Pigmented skin covered the wound 4 weeks after
      implantation. Hair shafts were visible at 12 weeks and prominent at 14 weeks.
      Histologically, the hRSK comprises an intact epidermis and dermis with mature
      hair follicles, sebaceous glands and most notably, and unique to this system,
      subcutis. Morphogenesis, differentiation, and maturation of the hRSK mirror the
      human fetal process. Human antigen markers demonstrate that the constituent cells
      are of human origin for at least 6 months. The degree of new skin formation is
      most complete when using tissue culture expanded cells from fetal skin, but it
      also occurs with expanded newborn and adult cells; however, no appendages formed
      when we grafted both adult dermal and epidermal cells. The hRSK system promises
      to be valuable as a laboratory model for studying biological, pathological, and
      pharmaceutical problems of human skin. 

PMID- 25074624
TI  - Through the lens of our cameras: children's lived experience with food security
      in a Canadian Indigenous community.
AB  - BACKGROUND: The related issues of food security and obesity among North American
      Indigenous children are serious public health concerns. This community-based
      participatory study sought to gain deeper understanding of young First Nation
      children's lived experience with food and to learn, from their perspective, about
      food security issues in their community. METHODS: In this Photovoice
      investigation 26 young children attending a rural reserve school in Canada were
      asked to take photographs of the food they ate. Nine high school students from
      the same school were trained as co-researchers: they interviewed the younger
      students, helped identify emerging themes and contributed to knowledge
      translation. Data analysis incorporated conventional content analysis, grounded
      theory's constant-comparative method, and examination of photos and texts.
      RESULTS: Five primary findings emerged from photographs and interviews: (1)
      children had a dualistic understanding of healthy vs. unhealthy foods; (2)
      packaged, quick-preparation foods played a dominant role in children's everyday
      food experiences; (3) families were critical to children's food-related
      experiences; (4) although traditional foods are viewed as central to Aboriginal
      health, few were depicted in the photographs; and (5) photos do not tell the
      whole story - despite the smaller numbers of fruits and vegetables in photos,
      children like to eat these foods when they are available at home. CONCLUSIONS:
      The study improved understanding of children's everyday food-related experiences,
      provided insight into community food security, and demonstrated the contribution
      of children and youth as experts on their lives and matters affecting them. A
      photobook representing findings provided a rich, visual tool for communicating
      the food-related experiences of children and messages about healthy eating within
      the school and to community members and leaders. Intervention efforts can build
      on participants' understanding of healthy versus unhealthy foods and on the
      critical role of family for healthy eating.

PMID- 25074620
TI  - Emotion and mood adaptations in the peripartum female:complementary contributions
      of GABA and oxytocin.
AB  - Peripartum hormones and sensory cues from young modify the maternal brain in ways
      that can render females either at risk for, or resilient to, elevated anxiety and
      depression. The neurochemical systems underlying these aspects of maternal
      emotional and mood states include the inhibitory neurotransmitter GABA and the
      neuropeptide oxytocin (OXT). Data from laboratory rodents indicate that increased
      activity at the GABA(A) receptor contributes to the postpartum suppression of
      anxiety-related behaviour that is mediated by physical contact with offspring,
      whereas dysregulation in GABAergic signalling results in deficits in maternal
      care, as well as anxiety- and depression-like behaviours during the postpartum
      period. Similarly, activation of the brain OXT system accompanied by increased
      OXT release within numerous brain sites in response to reproductive stimuli also
      reduces postpartum anxiety- and depression-like behaviours. Studies of peripartum
      women are consistent with these findings in rodents. Given the similar
      consequences of elevated central GABA and OXT activity on maternal anxiety and
      depression, balanced and partly reciprocal interactions between these two systems
      may be essential for their effects on maternal emotional and mood states, in
      addition to other aspects of postpartum behaviour and physiology.

PMID- 25074626
TI  - Drug reaction with eosinophilia and systemic symptoms during primary Epstein-Barr
      virus infection.
AB  - We report a drug reaction with eosinophilia and systemic symptoms case of primary
      Epstein-Barr virus (EBV) infection, in which the diagnosis was first confirmed by
      lymphocyte transformation tests (LTT). LTTs were positive for cefditoren-pivoxil
      and acetaminophen. LTT, EBV load, and anti-EBV antibodies could allow early
      diagnosis of drug reaction with eosinophilia and systemic symptoms, which
      masquerades with the clinical features of infectious mononucleosis. 

PMID- 25074627
TI  - Clinical features of patients with carbapenem nonsusceptible Klebsiella
      pneumoniae and Escherichia coli in intensive care units: a nationwide multicenter
      study in Taiwan.
AB  - BACKGROUND: Patients in intensive care units (ICUs) are especially prone to
      colonization and infection by carbapenem-resistant Enterobacteriaceae. We
      conducted a multicenter investigation to study the clinical and microbiological
      characteristics of patients with carbapenem nonsusceptible Klebsiella pneumoniae
      and Escherichia coli in ICUs of Taiwanese hospitals. METHODS: Patients with
      carbapenem nonsusceptible K. pneumoniae and E. coli in ICUs from nine medical
      centers and eight regional hospitals in Taiwan were enrolled in 2012. Carbapenem
      nonsusceptibility was defined as a minimum inhibitory concentration of at least 2
      mg/L for imipenem or meropenem. Clinical characteristics and risk factors for 30
      day mortality were analyzed. Isolates were screened for antibiotic susceptibility
      and beta-lactamase genes. RESULTS: A total of 66 cases infected (n = 46) or
      colonized (n = 20) with carbapenem nonsusceptible K. pneumoniae (n = 60) and E.
      coli (n = 6) were identified during the study period. Nineteen isolates had genes
      that encoded carbapenemases (28.8%), including Klebsiella pneumoniae
      carbapenemase-2 (KPC-2) (n = 14), imipenemase-8 (IMP-8) (n = 1), Verona integron
      encoded metallo-beta-lactamase (VIM) (n = 3), and New Delhi metallo-beta
      lactamase-1 (NDM-1) (n = 1). The in-hospital mortality associated with non
      susceptible K. pneumoniae and E. coli was 50%. The 30-day mortality of the 46
      patients with infection was 50%. Septic shock was the only independent risk
      factor for 30-day mortality in patients with infection. The 30-day mortality rate
      was similar between patients with combination therapy and monotherapy.
      CONCLUSION: Patients who acquired carbapenem nonsusceptible K. pneumoniae and E.
      coli in ICUs have a high mortality rate. Further clinical study is needed to deal
      with this emerging challenge.

PMID- 25074628
TI  - Development of a multiplex Luminex assay for detecting swine antibodies to
      structural and nonstructural proteins of foot-and-mouth disease virus in Taiwan.
AB  - BACKGROUND/PURPOSE(S): Foot-and-mouth disease (FMD) and swine vesicular disease
      (SVD) are serious vesicular diseases that have devastated swine populations
      throughout the world. The aim of this study was to develop a multianalyte
      profiling (xMAP) Luminex assay for the differential detection of antibodies to
      the FMD virus of structural proteins (SP) and nonstructural proteins (NSP).
      METHODS: After the xMAP was optimized, it detected antibodies to SP-VP1 and NSP
      3ABC of the FMD virus in a single serum sample. These tests were also compared
      with 3ABC polypeptide blocking enzyme-linked immunosorbent assay (ELISA) and
      virus neutralization test (VNT) methods for the differential diagnosis and
      assessment of immune status, respectively. RESULTS: To detect SP antibodies in
      661 sera from infected naive pigs and vaccinated pigs, the diagnostic sensitivity
      (DSn) and diagnostic specificity (DSp) of the xMAP were 90.0-98.7% and 93.0
      96.5%, respectively. To detect NSP antibodies, the DSn was 90% and the DSp ranged
      from 93.3% to 99.1%. The xMAP can detect the immune response to SP and NSP as
      early as 4 days postinfection and 8 days postinfection, respectively.
      Furthermore, the SP and NSP antibodies in all 15 vaccinated but unprotected pigs
      were detected by xMAP. A comparison of SP and NSP antibodies detected in the sera
      of the infected samples indicated that the results from the xMAP had a high
      positive correlation with results from the VNT and a 3ABC polypeptide blocking
      ELISA assay. However, simultaneous quantitation detected that xMAP had no
      relationship with the VNT. Furthermore, the specificity was 93.3-94.9% with 3ABC
      polypeptide blocking ELISA for the FMDV-NSP antibody. CONCLUSION: The results
      indicated that xMAP has the potential to detect antibodies to FMDV-SP-VP1 and NSP
      3ABC and to distinguish FMDV-infected pigs from pigs infected with the swine
      vesicular disease virus.

PMID- 25074629
TI  - Cryptococcal meningitis complicated with a large abdominal cyst mimicking acute
      pancreatitis.

PMID- 25074630
TI  - Elective change of surgeon during the OR day has an operationally negligible
      impact on turnover time.
AB  - STUDY OBJECTIVE: To compare turnover times for a series of elective cases with
      surgeons following themselves with turnover times for a series of previously
      scheduled elective procedures for which the succeeding surgeon differed from the
      preceding surgeon. DESIGN: Retrospective cohort study. SETTING: University
      affiliated teaching hospital. MEASUREMENTS: The operating room (OR) statistical
      database was accessed to gather 32 months of turnover data from a large academic
      institution. Turnover time data for the same-surgeon and surgeon-swap groups were
      batched by month to minimize autocorrelation and achieve data normalization. Two
      way analysis of variance (ANOVA) using the monthly batched data was performed
      with surgeon swapping and changes in procedure category as variables of turnover
      time. Similar analyses were performed using individual surgical services, hourly
      time intervals during the surgical day, and turnover frequency per OR as
      additional covariates to surgeon swapping. MAIN RESULTS: The mean (95% confidence
      interval [CI]) same-surgeon turnover time was 43.6 (43.2 - 44.0) minutes versus
      51.0 (50.5 - 51.6) minutes for a planned surgeon swap (P < 0.0001). This resulted
      in a difference (95% CI) of 7.4 (6.8 - 8.1) minutes. The exact increase in
      turnover time was dependent on surgical service, change in subsequent procedure
      type, time of day when the turnover occurred, and turnover frequency.
      CONCLUSIONS: The investigated institution averages 2.5 cases per OR per day. The
      cumulative additional turnover time (far less than one hour per OR per day) for
      switching surgeons definitely does not allow the addition of another elective
      procedure if the difference could be eliminated. A flexible scheduling policy
      allowing surgeon swapping rather than requiring full blocks incurs minimal
      additional staffed time during the OR day while allowing the schedule to be
      filled with available elective cases.

PMID- 25074631
TI  - Fruit intake decreases risk of incident type 2 diabetes: an updated meta
      analysis.
AB  - Association between fruit intake and risk of type 2 diabetes is inconsistent. In
      this study, we performed a meta-analysis of all prospective cohort studies to
      clarify the association between fruit intake and risk of type 2 diabetes.
      Relevant studies were identified by searches of the PubMed and Embase databases
      up to November 2013. The summary relative risks of association were obtained
      using a fixed- or random-effects model. A total of nine prospective studies
      (403,259 participants, including 27,940 with incident type 2 diabetes) from seven
      publications were included in the meta-analysis of fruit intake and risk of type
      2 diabetes. We found that individuals in the highest category of fruit intake had
      a reduced risk of type 2 diabetes (relative risk 0.92, 95 % confidence interval
      0.86-0.97, p = 0.003) compared to those in the lowest category, with moderate
      evidence of between-study heterogeneity (I (2) = 37.6 %, p = 0.12). There was an
      evident non-linear association of fruit intake with type 2 diabetes (P for
      nonlinearity <0.001). A non-linear threshold of 200 g/day of fruit intake was
      identified and the risk of type 2 diabetes reduced by about 13 % at this cut-off.
      Our findings are consistent with diet recommendations to consume about 200 g/day
      of fruits to prevent type 2 diabetes.

PMID- 25074632
TI  - Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists'
      treatment: a meta-analysis of randomized controlled trials.
AB  - Traditional anti-diabetic drugs may have negative or positive effects on risk of
      bone fractures. Yet the relationship between the new class glucagon-like peptide
      1 receptor agonists (GLP-1 RA) and risk of bone fractures has not been
      established. We performed a meta-analysis including randomized controlled trials
      (RCT) to study the risk of bone fractures associated with liraglutide or
      exenatide, compared to placebo or other active drugs. We searched MEDLINE,
      EMBASE, and clinical trial registration websites for published or unpublished
      RCTs comparing the effects of liraglutide or exenatide with comparators. Only
      studies with disclosed bone fracture data were included. Separate pooled analysis
      was performed for liraglutide or exenatide, respectively, by calculating Mantel
      Haenszel odds ratio (MH-OR). 16 RCTs were identified including a total of 11,206
      patients. Liraglutide treatment was associated with a significant reduced risk of
      incident bone fractures (MH-OR=0.38, 95% CI 0.17-0.87); however, exenatide
      treatment was associated with an elevated risk of incident bone fractures (MH
      OR=2.09, 95% CI 1.03-4.21). Publication bias and heterogeneity between studies
      were not observed. Our study demonstrated a divergent risk of bone fractures
      associated with different GLP-1 RA treatments. The current findings need to be
      confirmed by future well-designed prospective or RCT studies.

PMID- 25074633
TI  - Heparin-induced skin necrosis.

PMID- 25074634
TI  - Tuneable Fmoc-Phe-(4-X)-Phe-NH2 nanostructures by variable electronic
      substitution.
AB  - Supramolecular structures were produced by in situ enzymatic condensation of Fmoc
      Phe-(4-X), where X denotes electron withdrawing or donating groups, with Phe-NH2.
      The relative contribution of pi-stacking and H-bonding interactions can be
      regulated by the nature of X, resulting in tuneable nanoscale morphologies. 

PMID- 25074635
TI  - A systematic review of the efficacy of prophylactic control measures for
      naturally-occurring canine leishmaniosis, part I: vaccinations.
AB  - Canine leishmaniosis (CanL) is an important zoonotic disease; however, the
      efficacy of available vaccines for the prevention of naturally-occurring
      Leishmania infantum (L. infantum) infection in dogs remains unclear. The
      objective of this review was to determine the efficacy of currently available
      vaccines to prevent naturally-occurring L. infantum infection in dogs. Four
      bibliographic databases (CAB Direct 2011, Web of Science 2011, U.S. National
      Library of Medicine 2011 and Literatura Latino Americana e do Caribe em Ciencias
      da Saude) were searched along with eight sets of conference proceedings and the
      International Veterinary Information Service (IVIS) database, from 1980 to
      November 2012. Randomised controlled trials (RCTs), non-randomised clinical
      trials (NRCTs), cohort studies and case-control studies that investigated vaccine
      efficacy for natural L. infantum infection in dogs were eligible for inclusion.
      Two review authors independently assessed each study against the inclusion
      criteria, independently extracted relevant data from all included studies and
      assessed the risk of methodological shortcomings in each individual study. The
      odds ratio (OR) and absolute risk reduction (ARR) for dichotomous outcomes and
      mean difference for continuous outcomes were calculated. Meta-analysis was not
      performed due to heterogeneity of the studies identified. The search was
      conducted for all mitigations for CanL and yielded the title and abstract of 937
      articles, from which 84 articles were screened based on full text. Twelve studies
      on vaccinations (five RCTs, seven NRCTs) were identified. Ten studies were at a
      high risk of methodological shortcomings, whilst two were at an unclear risk. The
      use of 200 MUg ALM protein, Leishmune((r)), CaniLeish((r)), LiESAp with MDP, and
      ALM with BCG tended to significantly reduce the proportion of dogs infected with
      L. infantum based on either parasitological or serological evidence. The use of
      lyophilized protein vaccine significantly increased the proportion of dogs
      infected with L. infantum based on either parasitological or serological
      evidence. There is peer-reviewed evidence that control measures are effective in
      preventing CanL with the results suggesting that between 6 and 54% of infections
      could be prevented with vaccination. However, this evidence is based on a small
      number of RCTs, all of which are either at high or unclear risk of methodological
      shortcomings. Well-designed, adequately powered and properly reported randomised
      clinical trials are needed to clearly establish efficacy of vaccines as CanL
      control measures.

PMID- 25074636
TI  - Putative neuroprotective and neurotoxic kynurenine pathway metabolites are
      associated with hippocampal and amygdalar volumes in subjects with major
      depressive disorder.
AB  - Inflammation-related changes in the concentrations of kynurenine pathway
      metabolites occur in depression secondary to medical conditions but are not
      firmly established in primary mood disorders. Reductions in hippocampal and
      amygdalar volume that putatively reflect dendritic atrophy are widely reported in
      major depressive disorder (MDD). Here we tested whether the relative serum
      concentrations of putatively neuroprotective (kynurenic acid (KA)) and neurotoxic
      (3-hydroxykynurenine (3HK) and quinolinic acid (QA)) kynurenine pathway
      metabolites were altered in primary MDD and whether these metabolites were
      associated with hippocampal and amygdalar volume. A total of 29 moderately to
      severely depressed unmedicated subjects who met DSM-IV criteria for MDD and 20
      healthy controls (HCs) completed a structural MRI scan and provided blood sample
      for kynurenine metabolite analysis, performed using high-performance liquid
      chromatography with tandem mass spectrometry. Cytokine concentrations were
      measured with ELISA and gray matter volumes were measured with the automated
      segmentation software, FreeSurfer. An a priori defined variable of interest, the
      KA/QA ratio, a putative neuroprotective index, trended lower in the MDD versus
      the HC group and correlated negatively with anhedonia but positively with the
      total hippocampal and amygdala volume in the MDD subjects. The post hoc data
      reduction methods yielded three principal components. Component 1 (interleukin-1
      receptor antagonist, QA, and kynurenine) was significantly elevated in MDD
      participants versus the HCs, whereas component 2 (KA, tryptophan, and kynurenine)
      was positively correlated with hippocampal and amygdala volume within the MDD
      group. Our results raise the possibility that an immune-related imbalance in the
      relative metabolism of KA and QA predisposes to depression-associated dendritic
      atrophy and anhedonia. 

PMID- 25074637
TI  - Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working
      memory in schizotypal personality disorder.
AB  - Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a
      promising therapeutic approach to ameliorate schizophrenia-spectrum working
      memory deficits, but has yet to be rigorously evaluated clinically. This proof-of
      principle study sought to determine whether the active enantiomer of the
      selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate
      working memory impairments in unmedicated patients with schizotypal personality
      disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial
      of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30
      min) in medication-free patients with SPD (n=16) who met the criteria for
      cognitive impairment (ie, scoring below the 25th percentile on tests of working
      memory). We employed two measures of verbal working memory that are salient to
      schizophrenia-spectrum cognitive deficits, and that clinical data implicate as
      being associated with prefrontal D1 availability: (1) the Paced Auditory Serial
      Addition Test (PASAT); and (2) the N-back test (ratio of 2-back:0-back scores).
      Study procedures occurred over four consecutive days, with working memory testing
      on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with
      DAR-0100A was associated with significantly improved PASAT performance relative
      to placebo, with a very large effect size (Cohen's d=1.14). Performance on the N
      back ratio was also significantly improved; however, this effect rested on both a
      non-significant enhancement and diminution of 2-back and 0-back performance,
      respectively; therefore interpretation of this finding is more complicated. DAR
      0100A was generally well tolerated, with no serious medical or psychiatric
      adverse events; common side effects were mild to moderate and transient,
      consisting mainly of sedation, lightheadedness, tachycardia, and hypotension;
      however, we were able to minimize these effects, without altering the dose, with
      supportive measures, eg, co-administered normal saline. Although preliminary,
      these findings lend further clinical support to the potential of D1 receptor
      agonists to treat schizophrenia-spectrum working memory impairments. These data
      suggest a need for further studies with larger group sizes, serum DAR-0100A
      levels, and a more comprehensive neuropsychological battery. 

PMID- 25074639
TI  - Dopamine, locus of control, and the exploration-exploitation tradeoff.
AB  - Whether to continue to exploit a source of reward, or to search for a new one of
      potentially greater value, is a fundamental and underconstrained decision. Recent
      computational studies of this exploration-exploitation tradeoff have found that
      variability in exploration across individuals is influenced by a functional
      polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene, whose
      protein product degrades synaptically released dopamine. However, these and other
      genotype-phenotype associations have rarely been causally tested. To directly
      test this association and to evaluate additional behavioral characteristics,
      including perceived locus of control (LOC), here we used the COMT inhibitor
      tolcapone in a randomized, double-blind, counterbalanced, within-subject study of
      66 subjects genotyped for the Val158Met allele to assess the hypothesis that
      reducing COMT enzymatic activity interacts with genotype to increase uncertainty
      driven exploration. In keeping with our initial hypothesis, tolcapone led to an
      increase in exploratory, but not exploitative, behavior in Met/Met rather than
      Val/Val subjects. Independent of genotype, those subjects with a more external
      LOC also showed increases in uncertainty-driven exploration on tolcapone relative
      to placebo. However, we did not replicate our previous finding that Met/Met
      subjects show greater exploration at baseline. Together these findings support a
      model in which exploration is hypothesized to have a dopaminergic basis.
      Moreover, in keeping with findings in other behavioral and cognitive domains, the
      response to an increase in presumptively frontal dopamine is dependent upon
      baseline dopamine tone. 

PMID- 25074641
TI  - Conjugated polymer/nanocrystal nanocomposites for renewable energy applications
      in photovoltaics and photocatalysis.
AB  - Conjugated polymer/nanocrystal composites have attracted much attention for use
      in renewable energy applications because of their versatile and synergistic
      optical and electronic properties. Upon absorbing photons, charge separation
      occurs in the nanocrystals, generating electrons and holes for photocurrent flow
      or reduction/oxidation (redox) reactions under proper conditions. Incorporating
      these nanocrystals into conjugated polymers can complement the visible light
      absorption range of the polymers for photovoltaics applications or allow the
      polymers to sensitize or immobilize the nanocrystals for photocatalysis. Here,
      the current developments of conjugated polymer/nanocrystal nanocomposites for
      bulk heterojunction-type photovoltaics incorporating Cd- and Pb-based
      nanocrystals or quantum dots are reviewed. The effects of manipulating the
      organic ligands and the concentration of the nanocrystal precursor, critical
      factors that affect the shape and aggregation of the nanocrystals, are also
      discussed. In the conclusion, the mechanisms through which conjugated polymers
      can sensitize semiconductor nanocrystals (TiO2 , ZnO) to ensure efficient charge
      separation, as well as how they can support immobilized nanocrystals for use in
      photocatalysis, are addressed. 

PMID- 25074638
TI  - Relationship of monoamine oxidase-A distribution volume to postpartum depression
      and postpartum crying.
AB  - Postpartum depression (PPD) has a prevalence rate of 13% and a similarly high
      proportion of women report a subclinical state of one or more major depressive
      episode symptoms. The aim was to investigate whether monoamine oxidase-A (MAO-A)
      VT, an index of MAO-A density, is increased in the prefrontal and anterior
      cingulate cortex (PFC and ACC), during PPD or when a PPD spectrum symptom,
      greater predisposition to crying, is present. MAO-A is an enzyme that increases
      in density after estrogen decline, and has several functions including creating
      oxidative stress, influencing apoptosis and monoamine metabolism. Fifty-seven
      women were recruited including 15 first-onset, antidepressant naive, PPD
      subjects, 12 postpartum healthy who cry due to sad mood, 15 asymptomatic
      postpartum healthy women, and 15 healthy women not recently pregnant. Each
      underwent [(11)C]-harmine positron emission tomography scanning to measure MAO-A
      VT. Both PPD and greater predisposition to crying were associated with greater
      MAO-A VT in the PFC and ACC (multivariate analysis of variance (MANOVA), group
      effect, F21,135=1.856; p=0.019; mean combined region elevation 21% and 14% in PPD
      and crying groups, respectively, relative to postpartum asymptomatic). Greater
      MAO-A VT in the PFC and ACC represents a new biomarker in PPD, and the PPD
      symptom of predisposition to crying. Novel strategies for preventing PPD (and
      some PPD symptoms) may be possible by avoiding environmental conditions that
      elevate MAO-A level and enhancing conditions that normalize MAO-A level. These
      findings also argue for clinical trials in PPD with the newer, well-tolerated MAO
      A inhibitor antidepressants. 

PMID- 25074640
TI  - Effects of social interaction and warm ambient temperature on brain hyperthermia
      induced by the designer drugs methylone and MDPV.
AB  - 3,4-Methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone
      (MDPV) are new drugs of abuse that have gained worldwide popularity. These drugs
      are structurally similar to 3,4-methylenedioxymethamphetamine (MDMA) and share
      many of its physiological and behavioral effects in humans, including the
      development of hyperthermia during acute intoxication. Here, we examined the
      effects of methylone (1-9 mg/kg, s.c.) or MDPV (0.1-1.0 mg/kg, s.c.) on brain
      temperature homeostasis in rats maintained in a standard laboratory environment
      (single-housed in a quiet rest at 22  degrees C) and under conditions that model
      human drug use (social interaction and 29  degrees C ambient temperature). By
      simultaneously monitoring temperatures in the nucleus accumbens, temporal muscle,
      and facial skin, we assessed the effects of methylone and MDPV on intra-brain
      heat production and cutaneous vascular tone, two critical factors that control
      brain temperature responses. Both methylone and MDPV dose-dependently increased
      brain temperature, but even at high doses that induced robust locomotor
      activation, hyperthermia was modest in magnitude (up to ~2  degrees C). Both
      drugs also induced dose-dependent peripheral vasoconstriction, which appears to
      be a primary mechanism determining the brain hyperthermic responses. In contrast
      to the powerful potentiation of MDMA-induced hyperthermia by social interaction
      and warm ambient temperature, such potentiation was absent for methylone and
      minimal for MDPV. Taken together, despite structural similarities to MDMA,
      exposure to methylone or MDPV under conditions commonly associated with human
      drug use does not lead to profound elevations in brain temperature and sustained
      vasoconstriction, two critical factors associated with MDMA toxicity. 

PMID- 25074642
TI  - An 80.11% FF record achieved for perovskite solar cells by using the NH4Cl
      additive.
AB  - The light-absorbing perovskite layer fabricated using the NH4Cl additive shows
      high crystallinity and better morphology. The resulting solar cells gave a decent
      power conversion efficiency of 9.93% and a fill factor record of 80.11%. This
      work provides a very simple but effective approach to enhance the power
      conversion efficiency of perovskite solar cells. 

PMID- 25074643
TI  - Correlation of iron overload and glomerular filtration rate estimated by cystatin
      C in patients with beta-thalassemia major.
AB  - Historically, renal involvement has not been a commonly recognized complication
      in patients with beta-thalassemia major (beta-TM). Herein, we studied the impact
      of iron overload on glomerular filtration rate (GFR) estimated by cystatin C
      based GFR (Cyst C eGFR). We enrolled 149 patients with beta-TM in a cross
      sectional study in a single center in Oman. We investigated the correlation
      between measurement of serum ferritin and Cyst C eGFR. We used univariable linear
      regression to study the impact of serum ferritin on Cyst C eGFR and backwards
      stepwise regression to adjust for potential confounders. We included 78 males and
      71 females with a mean age of 17.3 +/- 9 years (range 2.5-38.5). Seventeen
      patients had diabetes mellitus. Patients were taking deferiprone (DFP) and
      deferoxamine (DFO) (26 patients), DFP (58 patients), deferasirox (DFX) (62
      patients) and one patient was taking only DFO. There was a very weak negative
      linear relationship between serum ferritin and Cyst C eGFR (correlation
      coefficient -0.25). In the univariable analyses, serum ferritin (p = 0.004),
      diabetes status (p < 0.001) and chelation therapy (p < 0.001) were statistically
      significant. In the multivariable model, age (p = 0.033), chelation with DFX (p =
      0.05) and diabetes status (p < 0.001) were statistically significant. We found a
      very weak inverse linear correlation between serum ferritin and Cyst C eGFR.
      However, when concomitant use of chelation therapy was considered, serum ferritin
      did not associate with glomerular function. Prospective and larger studies are
      needed to confirm these findings.

PMID- 25074645
TI  - Being a family systems thinker: a psychiatrist's personal odyssey.
AB  - This account traces the development of family systems thinking from early
      pioneering thinking and practices, through the development of institutions and
      professional definitions, and through challenges to family systems thinking and
      practice from the biomedical points of view. Throughout there is a strong
      conviction that "thinking family" is an essential core of effective mental health
      treatment, because families can heal. 

PMID- 25074646
TI  - Associations of common variants in methionine metabolism pathway genes with
      plasma homocysteine and the risk of type 2 diabetes in Han Chinese.
AB  - BACKGROUND/AIMS: An association of genetic variants of homocysteine (Hcy)
      metabolic genes with type 2 diabetes mellitus (T2DM) has been reported. The
      objective of the present study was to investigate the relationship between the
      genetic variants in Hcy metabolism-related genes and plasma Hcy levels and T2DM
      susceptibility in Han Chinese. METHODS: A total of 774 patients with T2DM and 500
      healthy individuals were recruited. Single-nucleotide polymorphism was determined
      by standard methods. RESULTS: The Hcy-increasing allele score was positively
      associated with plasma Hcy levels in both T2DM patients and healthy subjects (r =
      0.171 and 0.247, respectively). Subjects with the genotype CC of MTHFR
      (rs1801131) had a significantly higher likelihood of T2DM compared with subjects
      with the AA or AA+AC genotypes (OR = 1.93 for CC vs. AA, p = 0.041; OR = 3.13 for
      CC vs. AA+AC, p = 0.017, respectively). Subjects with the genotype AA of the
      MTHFD variant (rs2236225) had a significantly lower likelihood of T2DM compared
      with subjects with the GG or GG+GA genotypes (OR = 0.36 for AA vs. GG, p = 0.027;
      OR = 0.36 for AA vs. GG+GA, p = 0.017, respectively). In addition, the genotype
      CT+TT of the PEMT (rs4646356) variants displayed a significant association with
      an increased risk of T2DM (OR = 1.52 for CT+TT vs. CC, p = 0.042). CONCLUSIONS:
      MTHFR rs1801131 C allele and PEMT rs4646356 T allele were associated with a high
      risk of T2DM in these Han Chinese.

PMID- 25074647
TI  - [Veno-arterial extracorporeal membrane oxygenation. Indications, limitations and
      practical implementation].
AB  - Due to the technical advances in pumps, oxygenators and cannulas, veno-arterial
      extracorporeal membrane oxygenation (va-ECMO) or extracorporeal life support
      (ECLS) has been widely used in emergency medicine and intensive care medicine for
      several years. An accepted indication is peri-interventional cardiac failure in
      cardiac surgery (postcardiotomy low cardiac output syndrome). Furthermore,
      especially the use of va-ECMO for other indications in critical care medicine,
      such as in patients with severe sepsis with septic cardiomyopathy or in
      cardiopulmonary resuscitation has tremendously increased. The basic indications
      for va-ECMO are therapy refractory cardiac or cardiopulmonary failure. The
      fundamental purpose of va-ECMO is bridging the function of the lungs and/or the
      heart. Consequently, this support system does not represent a causal therapy by
      itself; however, it provides enough time for the affected organ to recover
      (bridge to recovery) or for the decision for a long-lasting organ substitution by
      a ventricular assist device or by transplantation (bridge to decision). Although
      the outcome for bridged patients seems to be favorable, it should not be
      forgotten that the support system represents an invasive procedure with
      potentially far-reaching complications. Therefore, the initiation of these
      systems needs a professional and experienced (interdisciplinary) team, sufficient
      resources and an individual approach balancing the risks and benefits. This
      review gives an overview of the indications, complications and contraindications
      for va-ECMO. It discusses its advantages in organ transplantation and transport
      of critically ill patients. The reader will learn the differences between
      peripheral and central cannulation and how to monitor and manage va-ECMO. 

PMID- 25074649
TI  - A novel stability and kinematics-driven trunk biomechanical model to estimate
      muscle and spinal forces.
AB  - An anatomically detailed eighteen-rotational-degrees-of-freedom model of the
      human spine using optimization constrained to equilibrium and stability
      requirements is developed and used to simulate several symmetric tasks in upright
      and flexed standing postures. Predictions of this stability and kinematics-driven
      (S+KD) model for trunk muscle forces and spine compressive/shear loads are
      compared to those of our existing kinematics-driven (KD) model where both
      translational and rotational degrees-of-freedom are included but redundancy is
      resolved using equilibrium conditions alone. Unlike the KD model, the S+KD model
      predicted abdominal co-contractions that, in agreement with electromyography
      data, increased as lifting height increased at a constant horizontal moment arm.
      The S+KD model, however, could not fully explain the CNS strategy in activating
      antagonistic muscles for most of the remaining tasks. Despite quite distinct
      activities in individual muscles, both models predicted L4-L5 intradiscal
      pressure that matched the in vivo data, the L4-S1 compression loads, and the sum
      of all trunk muscle forces. For modeling applications in ergonomics, where the
      compressive spine loads are of interest, the two models yielded <15% difference.
      In the field of rehabilitation, where detailed muscle forces are required, the
      S+KD model explained more properly the CNS strategy in activating the
      antagonistic muscles for some tasks. 

PMID- 25074648
TI  - Physical activity and telomere length in early stage breast cancer survivors.
AB  - INTRODUCTION: Telomere length (TL) is a biomarker of accumulated cellular damage
      and human aging. Evidence in healthy populations suggests that TL is impacted by
      a host of psychosocial and lifestyle factors, including physical activity. This
      is the first study to evaluate the relationship between self-reported physical
      activity and telomere length in early stage breast cancer survivors. METHODS: A
      cross-sectional sample of 392 postmenopausal women with stage I-III breast cancer
      at an outpatient oncology clinic of a large university hospital completed
      questionnaires and provided a blood sample. TL was determined using terminal
      restriction fragment length analysis of genomic DNA isolated from peripheral
      blood mononuclear cells. Physical activity was dichotomized into two groups (none
      versus moderate to vigorous) using the International Physical Activity
      Questionnaire. Multivariate linear and logistic regression analyses were
      performed to identify factors associated with mean TL and physical activity.
      RESULTS: Among participants, 66 (17%) did not participate in any physical
      activity. In multivariate model adjusted for age, compared to those who
      participated in moderate to vigorous physical activity, women who participated in
      no physical activity had significantly shorter TL (adjusted coefficient beta=
      0.22; 95% confidence interval (CI), -0.41 to -0.03; P=.03). Non-white race, lower
      education and depressive symptoms were associated with lack of self-reported
      physical activity (P<0.05 for all) but not TL. CONCLUSION: Lack of physical
      activity is associated with shortened TL, warranting prospective investigation of
      the potential role of physical activity on cellular aging in breast cancer
      survivors.

PMID- 25074650
TI  - Baseline drift removal and denoising of MCG data using EEMD: role of noise
      amplitude and the thresholding effect.
AB  - We adopt the Ensemble Empirical Mode Decomposition (EEMD) method, with an
      appropriate thresholding on the Intrinsic Mode Functions (IMFs), to denoise the
      magnetocardiography (MCG) signal. To this end, we discuss the two associated
      problems that relate to: (i) the amplitude of noise added to the observed signal
      in the EEMD method with a view to prevent mode mixing and (ii) the effect of
      direct thresholding that causes discontinuities in the reconstructed denoised
      signal. We then denoise the MCG signals, having various signal-to-noise ratios,
      by using this method and compare the results with those obtained by the standard
      wavelet based denoising method. We also address the problem of eliminating the
      high frequency baseline drift such as the sudden and discontinuous changes in the
      baseline of the experimentally measured MCG signal using the EEMD based method.
      We show that the EEMD method used for denoising and the elimination of baseline
      drift is superior in performance to other standard methods such as wavelet based
      techniques and Independent Component Analysis (ICA). 

PMID- 25074651
TI  - Temporospatial localization of dentine matrix protein 1 following direct pulp
      capping with calcium hydroxide in rat molars.
AB  - AIM: To examine the temporospatial expression of dentine matrix protein 1 (DMP1;
      a noncollagenous protein involved in mineralized tissue formation), osteopontin
      (another noncollagenous protein detected during reparative dentinogenesis) and
      nestin (a marker of differentiating/differentiated odontoblasts), following
      direct pulp capping with calcium hydroxide in rat molars. METHODOLOGY: The
      maxillary first molars of 8-week-old Wistar rats had their pulps exposed and
      capped with calcium hydroxide. The pulp-capped teeth were collected from 6 h to
      14 days postoperatively and processed for immunohistochemistry for DMP1,
      osteopontin and nestin. Cell proliferation was monitored using 5-bromo-2'
      deoxyuridine (BrdU) labelling. RESULTS: The capped pulps initially exhibited
      superficial necrotic changes followed by the formation of new matrix and its
      mineralization. DMP1 immunoreactivity was observed in the matrix beneath the
      necrotic layer from 6 h onwards and present in the outer portion of the newly
      formed mineralized matrix from 7 days onwards. Osteopontin displayed a similar
      expression pattern, although it occupied a narrower area than DMP1 at 6 and 12 h.
      Nestin-immunoreactive cells appeared beneath the DMP1-immunoreactive area at 1
      day, were distributed beneath the newly formed matrix at 5 days and exhibited
      odontoblast-like morphology by 14 days. BrdU-positive cells significantly
      increased at 2 and 3 days (P < 0.05) and then decreased. CONCLUSIONS: The
      deposition of DMP1 at exposed pulp sites preceded the appearance of nestin
      immunoreactive cells, active cell proliferation and new matrix formation after
      pulp capping with calcium hydroxide in rat molars, suggesting that DMP1 acts as a
      trigger of pulp repair. The colocalization of DMP1 and osteopontin suggests that
      these two proteins play complementary roles.

PMID- 25074652
TI  - Attempt to run urinary protein electrophoresis using capillary technique.
AB  - The study of urinary protein has a predominant place in the diagnosis of kidney
      disease. The most common technique is agarose gel electrophoresis (AGE). For
      several years, the technique of choice applied to the analysis of serum proteins
      has been CE, a system that uses capillary fused silica, subjected to high voltage
      to separate and measure serum proteins. The purpose of this paper was to perform
      capillary electrophoresis on urinary proteins which, at present, are not
      interpretable due to the many nonspecific peaks visible when using gel
      electrophoresis. In order to carry out our research, we used a capillary V8
      analyzer together with an agarose gel system from the same company. AGE was taken
      as the reference method, for which urine was used without any pretreatment. For
      the V8 system, urine was subjected to purification on granular-activated carbon
      and then inserted into the V8 analyzer, selecting a program suitable for liquids
      with low protein content. We examined 19 urine samples collected over 24 hrs from
      both hospitalized and external patients with different types of proteinuria plus
      a serum diluted 1/61 considered as a control to recognize the bands. Both methods
      showed the same protein fractions and classified the proteinuria in a similar
      way. 

PMID- 25074653
TI  - Significance of the mass-compression effect of postlaminectomy/laminotomy
      fibrosis on histological changes on the dura mater and nerve root of the cauda
      equina: an experimental study in rats.
AB  - PURPOSE: The precise mechanism and pathological role of
      postlaminectomy/laminotomy fibrosis (PLF) in postoperative neurological deficits
      have not been established. Many studies use magnetic resonance imaging (MRI) to
      prove that there is no consistent correlation between PLF and postoperative
      neurological deficits and back pain (PNDBP). Therefore, we assumed that the
      direct-compression effect may not be the only factor but that other neurological
      deficits associated with pathological mechanisms should exist and need more
      investigation. The purpose of this study was to compare over time the differences
      and changes in histopathological properties of PLF in rats. METHODS: We used a
      rat model with walking-track analysis for neurologic evaluation, grading scale to
      evaluate PLF, histomorphometric measurements of dura sac diameter, and
      histological tissue reactions (dura mater and spinal rootlets) juxtaposed to the
      postlaminectomy/laminotomy defect. The 54 adult Sprague-Dawley rats were divided
      into laminotomy (n = 18), laminectomy (n = 18), and sham-operation groups (n =
      18). All groups were subdivided into three equal subgroups based on different
      postoperative time points (1, 2, and 3 months). All sections of vertebral column
      were stained with hematoxylin and eosin and with Masson's trichrome. RESULTS: The
      results showed that only a slight compression effect reflected by nonsignificant
      changes in the maximum anterior-posterior diameters within the dura sac, in the
      walking tract test, and increased grades of PLF over time. In addition,
      significant pathological inflammatory changes, such as thickening of the dura
      mater, axonal swelling, and neovascularization, were found in the post
      laminectomy/laminotomy groups at each time point. CONCLUSION: Laminectomy
      /laminotomy-related inflammation may lead to PLF, and these pathological changes
      may be the main cause of postoperative neurological deficits. These findings show
      that research on preventing PLF should include perioperative modulation of
      inflammatory reactions induced by laminectomy/laminotomy.

PMID- 25074654
TI  - [Oculomotor system and multiple sclerosis].
AB  - Disorders of ocular motility due to multiple sclerosis can cause significant
      symptoms, such as blurred vision, diplopia, oscillopsia and dizziness. The
      spectrum of ocular motor disorders is broad due to the multifocal nature of the
      disease. The most frequent disorders include dysmetric saccades, impaired smooth
      pursuit, internuclear ophthalmoplegia (INO), impaired vestibulo-ocular reflex,
      misalignment of visual axes, impaired vergence and gaze-evoked nystagmus.
      Patients with abnormal eye movements are more handicapped than patients without
      ocular motility disorders as eye movement disorders and gait disturbances are
      both caused by an extensive involvement of the brainstem and cerebellum. 

PMID- 25074655
TI  - [A 23-gauge pars plana vitrectomy after induction of general anesthesia: effect
      of additional retrobulbar anesthesia on postoperative pain].
AB  - PURPOSE: Some studies have shown a significant reduction of postoperative pain by
      additional regional anesthesia in 20-gauge pars plana vitrectomy (20-G-ppV) with
      the patient under general anesthesia (AN). This observational study examined
      whether the advantages of additional retrobulbar anesthesia can also be observed
      with 23-gauge vitrectomy in AN. MATERIAL AND METHODS: Surgery was performed in
      130 patients under AN of which 88 received an additional retrobulbar block (group
      AN+) and 42 patients were treated without additional injection of retrobulbar
      anesthesia (group AN) using bupivacaine 0.5 % and mepivacaine 1%. The AN was
      performed with fentanyl and propofol. Postoperatively, the subjective patient
      pain was recorded using a numeric scale and the use and amount of analgesic drugs
      in the postoperative course were monitored. RESULTS: The mean age of the patients
      was 53.6 +/- 16.8 years, 52.6% of the patients were male, 31.5% were staged as
      American Society of Anesthesiologists (ASA) level I, 52.3% as ASA II and 15.4% as
      ASA III. At no time did the study show a statistically significant difference in
      pain frequency, intensity and analgesic consumption. However, the results suggest
      that patients in the AN+ group tended to experienced delayed and more intense
      postoperative pain, which is also reflected in the postoperative use of pain
      relief medications. CONCLUSIONS: This study did not show any advantage by
      additional retrobulbar anesthesia regarding postoperative analgesia compared to
      an adequate treatment with peripheral acting analgesics during surgery and the
      early postoperative period.

PMID- 25074656
TI  - Relationship of meeting physical activity guidelines with quality-adjusted life
      years.
AB  - OBJECTIVE: The quality-adjusted life-year (QALY) is a standard outcome measure
      used in cost-effectiveness analyses. This study investigates whether attainment
      of federal physical activity guidelines is associated with higher QALY estimates
      among adults with or at an increased risk for knee osteoarthritis. METHODS: This
      is a prospective study of 1794 Osteoarthritis Initiative participants. Physical
      activity was measured using accelerometers at baseline. Participants were
      classified as (1) Meeting Guidelines [>=150min of moderate-to-vigorous (MV)
      activity per week acquired in sessions >=10min], (2) Insufficiently Active (>=1
      MV session[s]/week but below the guideline), or (3) Inactive (zero MV
      sessions/week). A health-related utility score was derived from participant
      responses to the 12-item Short-Form Health Survey at baseline and 2 years later.
      The QALY was calculated as the area under utility curve over 2 years. The
      relationship of physical activity level to median QALY adjusted for socioeconomic
      and health factors was estimated using quantile regression. RESULTS: Relative to
      the Inactive group, median QALYs over 2 years were significantly higher for the
      Meeting Guidelines (0.112, 95% CI: 0.067-0.157) and Insufficiently Active (0.058,
      95% CI: 0.028-0.088) groups, controlling for socioeconomic and health factors.
      CONCLUSION: We found a significant graded relationship between greater physical
      activity level and higher QALYs. Using the more conservative estimate of 0.058,
      if an intervention could move someone out of the Inactive group and costs <$2900
      over 2 years, it would be considered cost effective. Our analysis supports
      interventions to promote physical activity even if recommended levels are not
      fully attained.

PMID- 25074657
TI  - Risk of malignancy in patients with giant cell arteritis and polymyalgia
      rheumatica: a systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate the association between giant cell arteritis
      (GCA)/polymyalgia rheumatica (PMR) and malignancy risk. METHODS: We conducted a
      systematic review and meta-analysis of cohort studies that reported relative
      risk, hazard ratio, or standardized incidence ratio (SIRs) with 95% confidence
      comparing malignancy risk in patients with GCA/PMR versus non-GCA/PMR
      participants. Pooled risk ratios and 95% confidence intervals were calculated
      using a random-effect, generic inverse variance method. RESULT: A total of six
      studies were identified and included in our data analysis. The pooled risk ratio
      of malignancy in patients with GCA/PMR was 1.14 (95% CI: 1.05-1.22). The risk was
      higher in the first 6-12 months after diagnosis with the pooled risk ratio of
      2.16 (95% CI: 1.85-2.53). However, when we performed a sensitivity analysis that
      excluded one study with a potential selection bias, the pooled risk ratio
      decreased and did not achieve statistical significance. CONCLUSION: Our study
      demonstrated a low but statistically significant increased malignancy risk among
      patients with GCA/PMR. However, when we excluded one study with potential
      selection bias, the new pooled risk ratio did not achieve statistical
      significance.

PMID- 25074660
TI  - Epithelial to mesenchymal transition expression profiles as predictive biomarkers
      of recurrence following resection of HCC: implications for current clinical use
      and future stratification for systemic therapy.

PMID- 25074658
TI  - Antibiotic susceptibility of ica-positive and ica-negative MRSA in different
      phases of biofilm growth.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a clinically
      relevant pathogen because of its resistance to antibiotics and its ability to
      form potent biofilm. Both ica-negative as well as ica-positive MRSA strains are
      known to produce biofilm. In the present study, these strains were grown in
      biofilm mode and susceptibility of these to antibiotics was assessed. Our study
      suggests that antibiotic susceptibility of MRSA biofilm depends on the
      biochemical composition of its matrix. The biofilm matrix of ica-positive MRSA
      was mainly composed of poly-intercellular adhesion (PIA), whereas eDNA was a
      major constituent of ica-negative MRSA. The results showed that MRSA in
      planktonic growth was susceptible to clindamycin, vancomycin and minocycline.
      However, the MIC and MBC of vancomycin for the mature biofilm of ica-negative
      MRSA was 16 and 32 MUg ml(-1), respectively. On the contrary, the MIC and MBC of
      vancomycin for ica-positive MRSA was >1024 MUg ml(-1). The effect of vancomycin
      and minocycline on young and old biofilms was also determined. Vancomycin was
      quite effective in eradicating the young biofilm formed by ica-negative MRSA;
      however, it was completely ineffective on the biofilm of ica-positive MRSA.
      Minocycline at its highest clinical achievable concentration was found to be
      quite effective in eradicating the young biofilm formed by both the strains. The
      enzyme-linked immunosorbent assay (ELISA) results and dot blot assay suggest that
      the presence of ica locus influenced PIA production, which probably contributed
      towards the failure of vancomycin in eradicating the biofilm formed by ica
      positive strain. However, none of the antibiotics used in this study was
      effective in eradicating the mature biofilms. 

PMID- 25074661
TI  - Does BMI affect the accuracy of preoperative axillary ultrasound in breast cancer
      patients?
AB  - INTRODUCTION: Obesity affects 36 % of American women and is a well-documented
      breast cancer risk factor. Preoperative axillary ultrasound (AUS) is used
      routinely for axillary staging in newly diagnosed breast cancer patients;
      However, the impact of obesity on the usefulness of AUS is unknown. Our aim was
      to evaluate the effect of body mass index (BMI) on the performance of AUS.
      METHODS: From our prospective breast surgery database, we identified 1,510
      consecutive invasive breast cancers in patients undergoing primary surgery,
      including axillary operation, from January 2010 to July 2013. Preoperative AUS
      was performed in 1,375 cases (91 %). We analyzed patient, pathology and imaging
      data. RESULTS: Median BMI was 27.4 and 479 patients (36 %) were classified as
      obese (BMI >= 30). Most tumors were T1 (71 %) and estrogen receptor-positive (87
      %). AUS was suspicious in 401 (29 %) patients, of whom 374 had ultrasound-guided
      lymph node fine-needle aspiration (FNA). Overall, 124 patients (33.2 %) were FNA
      positive. FNA identified disease preoperatively in 35.8 % of node-positive obese
      patients. For all BMI categories (normal, overweight, obese), AUS was predictive
      of pathologic nodal status (p < 0.0001). AUS sensitivity did not differ across
      BMI categories, while specificity and accuracy were better for overweight (p =
      0.001 and 0.008, respectively) and obese (p = 0.007 and 0.02, respectively)
      patients, than for normal-BMI patients. CONCLUSIONS: Despite theoretical concern
      regarding both potential technical challenges and obesity-related lymph node
      alterations, the sensitivity of preoperative AUS for detecting nodal metastasis
      was similar in obese and non-obese patients, while specificity was better in
      obese patients. Preoperative AUS is valuable for preoperative nodal staging of
      obese breast cancer patients.

PMID- 25074659
TI  - Stability, compatibility and microbiological activity studies of meropenem
      clavulanate potassium.
AB  - Meropenem (MEM) and clavulanate potassium have been reported to demonstrate
      highly effective activity against Mycobacterium tuberculosis. There have been no
      reports on research into the complex of these chemotherapeutics concerning their
      mutually dependent stability or microbiological action on other microorganisms.
      Stability and compatibility studies of MEM/clavulanate potassium were conducted
      by using an HPLC-DAD method. The antibacterial activity of MEM/clavulanate
      potassium was tested in vitro against a selection of indicator bacteria strains
      by determining the MIC as well as analyzing the kinetics of changes in the
      concentrations of Pseudomonas aeruginosa, Staphylococcus aureus and Listeria
      monocytogenes caused by the action of MEM/clavulanate potassium. The stability
      and compatibility of MEM/clavulanate potassium were examined in aqua pro
      iniectione, 0.9% NaCl and 5% glucose at room temperature and at 5  degrees C. The
      degradation rates of MEM/clavulanate potassium depended on the type of infusion
      solvent used. Although in aqueous solutions of MEM/clavulanate potassium neither
      compound showed any mutual impact on the rate of degradation, clavulanate
      potassium was more labile than MEM. The synergy between these two resulted in a
      significantly lower value of MIC as compared to the values observed for the
      individual activity of either compound. The infusion solvent in which
      compatibility is observed between the components of the mixture MEM/clavulanate
      potassium is aqua pro iniectione. The complex MEM/clavulanate potassium
      demonstrates synergic antibacterial activity against P. aeruginosa, S. aureus and
      L. monocytogenes. 

PMID- 25074662
TI  - Advanced locoregional therapies in breast.
AB  - BACKGROUND: Advanced locoregional therapies continue to advance the treatment of
      breast cancer. These techniques are geared towards optimizing oncologic and
      aesthetic outcome as well as decreasing and treating morbidity. We present a
      selection of specialized locoregional therapies dedicated to the optimization of
      breast cancer treatment. METHODS: Locoregional therapies for breast cancer are
      presented to address breast conservation techniques, lipofilling techniques,
      reconstruction techniques for nipple-sparing mastectomy, re-irradiating the
      breast, axillary reverse mapping, and vascularized lymph node transfer. RESULTS:
      We present a synopsis of identified breast locoregional therapies targeted to
      address optimal oncologic and aesthetic outcome as well as decrease and treat
      morbidity.

PMID- 25074663
TI  - The use of modified four-dimensional computed tomography in patients with primary
      hyperparathyroidism: an argument for the abandonment of routine sestamibi single
      positron emission computed tomography (SPECT).
AB  - BACKGROUND: Four-dimensional computed tomography (4D CT) has emerged as an
      extremely sensitive preoperative imaging modality for primary hyperparathyroidism
      compared with the historical use of sestamibi and ultrasound (US). Specialized
      volume rendering and technical modifications further enhance this technique for
      operative guidance while reducing radiation exposure. METHODS: Patients
      undergoing parathyroidectomy for primary hyperparathyroidism from December 2010
      to September 2013, carried out by two surgeons at a tertiary cancer center, were
      evaluated. Comparison was made between the three imaging modalities (4D CT,
      sestamibi, and US) for preoperative localization rate and accuracy. Biochemical
      parameters and radiation exposure were also analyzed. RESULTS: A total of 202
      patients were identified from the database and 200 patients were included in the
      analysis. All patients underwent 4D CT (100 %), 185 sestamibi (92.5 %) and 186 US
      (93 %). In patients with single-gland disease (n = 153), 4D CT, sestamibi, and US
      were positive in 96 %, 65.4 % and 57.7 % of patients, respectively and, when
      positive, were accurately localized in 97.2 %, 93.4 % and 96.3 % of patients,
      respectively. In patients with multigland disease (MGD) [n = 47], 4D CT,
      sestamibi, and US predicted MGD in 32 %, 0 %, and 13.6 % of patients,
      respectively. With our technique modification, radiation exposure from 4D CT
      approached that of sestamibi. CONCLUSIONS: Low-dose, modified 4D CT with volume
      rendering when compared with sestamibi has a statistically significant higher
      positivity rate, improved accuracy rate, provides excellent images, superior
      surgical planning, and has a comparable radiation exposure risk profile.
      Consideration should be made for the abandonment of routine sestamibi single
      positron emission computed tomography (SPECT), with 4D CT as the preoperative
      imaging modality of choice.

PMID- 25074664
TI  - Cancer-specific mortality and competing mortality in patients with head and neck
      squamous cell carcinoma: a competing risk analysis.
AB  - BACKGROUND: The objective of this study was to estimate probabilities of cancer
      specific death and competing death for patients with head and neck squamous cell
      carcinoma (HNSCC). In addition, we attempted to construct competing risk
      nomograms to predict prognosis for patients with HNSCC using a large population
      based cohort. METHODS: Patients diagnosed with nonmetastatic HNSCC between 2000
      and 2010 were identified from the Surveillance Epidemiology and End Results
      Program to form the analytic cohort. We estimated cumulative incident function
      (CIF) of cancer-specific mortality and competing mortality. Nomograms for
      predicting probability of death were built with proportional subdistribution
      hazard models. RESULTS: The study cohort included 23,494 patients with HNSCC. The
      5-year CIF for cancer-specific death and competing death were 26.7 % (95 %
      confidence interval [CI] 26-27.3 %) and 12.7 % (95 % CI 12.2-13.3 %),
      respectively; 10-year CIF were 32.8 % (95 % CI 31.9-33.6 %) and 23 % (95 % CI
      22.1-24 %), respectively. On multivariate analysis, increasing cause-specific
      mortality was associated with increasing age, increasing tumor size, black race,
      single status, advanced T and N classifications, and high tumor grade. Increasing
      probability of competing mortality had a relationship with increasing age, male,
      black race, single status and nonradiotherapy. Models showed good accuracy with c
      index of 0.73 for cause-specific mortality model and 0.69 for competing mortality
      model. CONCLUSIONS: We constructed competing risk nomograms for HNSCC using
      population-based data. The model used for building nomograms represented good
      performance. These nomograms can serve to guide management of patients with
      HNSCC.

PMID- 25074665
TI  - False negative cytology in large thyroid nodules.
AB  - BACKGROUND: Controversy exists regarding the accuracy of fine-needle aspiration
      (FNA) in large thyroid nodules. Recent surgical series have documented false
      negative rates ranging from 0.7 to 13 %. We examined the accuracy of benign FNA
      cytology in patients with thyroid nodules >=3 cm who underwent surgical resection
      and identified features characteristic of false-negative results. METHODS: We
      retrospectively studied all thyroidectomy specimens between January 2009 and
      October 2011 and identified nodules >=3 cm with corresponding benign preoperative
      FNA cytology. We collected clinical information regarding patient demographics,
      nodule size, symptoms, sonographic features, FNA results, and final surgical
      pathology. For comparison, we analyzed nodules <3 cm from this cohort also with
      benign FNA cytology. RESULTS: A total of 323 nodules with benign preoperative
      cytology were identified. Eighty-three nodules were <3 cm, 94 nodules were 3-3.9
      cm, and 146 nodules were >=4 cm in size. The false-negative rate was 11.7 % for
      all nodules >=3 cm and 4.8 % for nodules <3 cm (p = 0.03). Subgroup analysis of
      nodules >=3 cm revealed a false-negative rate of 12.8 % for nodules 3-3.9 cm and
      11 % for nodules >=4 cm. Age >=55 years and asymptomatic clinical status were the
      only patient characteristics that reached statistical significance as risk
      factors. Final pathology of the false-negative specimens consisted mainly of
      follicular variant of papillary thyroid cancer and follicular thyroid cancer.
      CONCLUSIONS: When referred for thyroidectomy, patients with large thyroid nodules
      demonstrate a modest, yet significant, false-negative rate despite initial benign
      aspiration cytology. Therefore, thyroid nodules >=3 cm may be considered for
      removal even when referred with benign preoperative cytology.

PMID- 25074666
TI  - Population-based assessment of currently proposed ideals of nasal tip projection
      and rotation in young women.
AB  - IMPORTANCE: There is no universally accepted quantitative metric that defines the
      ideal nasal tip rotation and projection. OBJECTIVE: To identify the ideal nasal
      tip projection (NTP) and rotation by using 3 classic NTP methods (Crumley 1,
      Crumley 2, and Goode). DESIGN, SETTING, AND PARTICIPANTS: Lateral facial
      portraits of normal-appearing white women aged 18 to 25 years were selected from
      a previously validated and attractiveness-scored database of images. Each image
      was digitally modified to fit the NTP ideals outlined by the Crumley 1, Crumley
      2, and Goode methods with columellar facial angles (rotation metric) of 96
      degrees , 101 degrees , 106 degrees , 111 degrees , and 116 degrees  (15 modified
      images per portrait). These variants were incorporated into electronic surveys
      that were distributed to traditional focus-group and online social-network
      participants. Analysis was performed using paired comparison analysis, a consumer
      preference research analytic. The traditional focus-group participants were
      undergraduate students at the University of California, Irvine, whose online
      social-network contacts were also used. MAIN OUTCOMES AND MEASURES: Mean ranks.
      RESULTS: There were no significant differences in preference between the
      traditional focus-group (n = 106) and online participants (n = 3872) (P > .05).
      The most preferred rotation variant for all 3 NTP methods was 106 degrees 
      (Crumley 1: mean rank, 2.11 [95% CI, 2.07-2.16]; Crumley 2: mean rank, 2.07 [95%
      CI, 2.02-2.12]; and Goode: mean rank, 2.05 [95% CI, 1.99-2.11]; P < .001).
      Crumley 1 was considered to be the most attractive NTP method (mean rank, 1.84
      [95% CI, 1.82-1.85]; P < .001) overall and was the most preferred NTP method for
      faces of above-average attractiveness (mean rank, 1.78 [95% CI, 1.76-1.80]; P <
      .001). No significantly preferred NTP method was found for faces of average
      attractiveness (P > .05). The most aesthetic combination of tip rotation and
      projection was a columellar facial angle of 106 degrees  with the Crumley 1 tip
      projection. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first
      population-based study to attempt to simultaneously determine the ideal NTP and
      rotation. Each classic NTP method uses measurements dependent on both projection
      and rotation; thus, ideal rotation for each NTP method must be determined before
      comparison of the ideals. A rotation of 106 degrees  (columellar facial angle)
      was found to be the most aesthetic. The Crumley 1 method was determined to be the
      most attractive nasal tip variant overall. LEVEL OF EVIDENCE: NA.

PMID- 25074667
TI  - Transplantation in inborn errors of metabolism: current considerations and future
      perspectives.
AB  - Inborn errors of metabolism (IEM) comprise an assorted group of inherited
      diseases, some of which are due to disordered lysosomal or peroxisomal function
      and some of which might be improved following haemopoietic cell transplantation
      (HCT). In these disorders, the onset in infancy or early childhood is typically
      accompanied by rapid deterioration, resulting in early death in the more severe
      phenotypes. Timely diagnosis and immediate referral to an IEM specialist are
      essential steps in optimal management. Treatment recommendations are based on the
      diagnosis, its phenotype, rate of progression, prior extent of disease, family
      values and expectations and the risks and benefits associated with available
      therapies, including HCT. International collaborative efforts are of utmost
      importance in determining outcomes of therapy for these rare diseases, and have
      improved those outcomes significantly over recent decades. This discussion
      focuses on HCT in IEM, providing an international perspective on progress,
      limitations, and future directions.

PMID- 25074668
TI  - Physicochemical properties, form, and formulation selection strategy for a
      biopharmaceutical classification system class II preclinical drug candidate.
AB  - This work summarizes the pharmaceutical evaluation of a preclinical drug
      candidate with poor physicochemical properties. Compound 1 is a weakly basic, GPR
      119 agonist designated to Biopharmaceutics Classification System Class II because
      of good permeability in a Caco-2 cell line model and poor solubility. Compound 1
      showed good oral bioavailability from a solution formulation at low doses and
      oral exposure sufficient for toxicological evaluation at high doses from a
      nanosuspension of Form A-the only known polymorph of 1 during drug discovery. The
      identification of the thermodynamically stable polymorph, Form B, during early
      development adversely affected the bioperformance of the nanosuspension. The poor
      solubility of Form B resulted in a significant reduction in the oral exposure
      from a nanosuspension to a level that was insufficient for toxicological
      evaluation of compound 1. Subsequent to the discovery of Form B, multiple form
      and formulation engineering strategies were evaluated for their ability to
      enhance the oral exposure of 1. Formulations based on cocrystals and amorphous
      solid dispersions showed a statistically significant increase in exposure,
      sixfold and sevenfold, respectively, over the benchmark formulation, a suspension
      of Form B. The physicochemical characterization of 1, and the solid form and
      formulation engineering approaches explored to address the insufficient oral
      exposure of Form B are discussed along with insights on improving the
      physicochemical properties of the follow-on drug candidates in discovery.

PMID- 25074671
TI  - Chain flexibility for tuning effective interactions in blends of polymers and
      polymer-grafted nanoparticles.
AB  - We present molecular dynamics simulations of polymer-grafted nanoparticles in a
      homopolymer matrix to demonstrate the effect of chain flexibility on the
      potential of mean force (PMF) between various species in the nanocomposite. For a
      relatively high grafting density of Sigmag = 0.76 chains/sigmap(2) (where sigmap
      is the polymer monomer diameter), when the brush chain length is significantly
      smaller than (<~ 1/4) the matrix chain length, the brushes exhibit autophobic
      dewetting with matrix polymers resulting in a strong attractive well in the
      particle-particle PMF. As the chain flexibility is decreased, we observe
      significant changes in particle-particle and particle-matrix PMFs that are
      strongly coupled with the length (or molecular weight) of grafted chains. For low
      molecular weight grafted chains, the change in the well-depth of particle
      particle PMFs, with increasing chain stiffness, is non-monotonous, while that for
      longer grafted chains (still shorter than matrix chains), the attractive well
      exhibits a monotonous decrease in its depth. The particle-matrix PMF and the
      matrix penetration depth into the brush layer indicate that wetting of the
      grafted layer by matrix chains is enhanced with increasing chain stiffness.

PMID- 25074669
TI  - Effects of selective inhibitors of Aurora kinases on anaplastic thyroid carcinoma
      cell lines.
AB  - Aurora kinases are serine/threonine kinases that play an essential role in cell
      division. Their aberrant expression and/or function induce severe mitotic
      abnormalities, resulting in either cell death or aneuploidy. Overexpression of
      Aurora kinases is often found in several malignancies, among which is anaplastic
      thyroid carcinoma (ATC). We have previously demonstrated the in vitro efficacy of
      Aurora kinase inhibitors in restraining cell growth and survival of different ATC
      cell lines. In this study, we sought to establish which Aurora might represent
      the preferential drug target for ATC. To this end, the effects of two selective
      inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) on four human ATC cell
      lines (CAL-62, BHT-101, 8305C, and 8505C) were analysed. Both inhibitors reduced
      cell proliferation in a time- and dose-dependent manner, with IC50 ranges of 44.3
      134.2 nM for MLN8237 and of 9.2-461.3 nM for AZD1152. Immunofluorescence
      experiments and time-lapse videomicroscopy yielded evidence that each inhibitor
      induced distinct mitotic phenotypes, but both of them prevented the completion of
      cytokinesis. As a result, poliploidy increased in all AZD1152-treated cells, and
      in two out of four cell lines treated with MLN8237. Apoptosis was induced in all
      the cells by MLN8237, and in BHT-101, 8305C, and 8505C by AZD1152, while CAL-62
      exposed to AZD1152 died through necrosis after multiple rounds of
      endoreplication. Both inhibitors were capable of blocking anchorage-independent
      cell growth. In conclusion, we demonstrated that either Aurora-A or Aurora-B
      might represent therapeutic targets for the ATC treatment, but inhibition of
      Aurora-A appears more effective for suppressing ATC cell proliferation and for
      inducing the apoptotic pathway.

PMID- 25074670
TI  - A biodistribution study of PEGylated PCL-based nanoparticles in C57BL/6 mice
      bearing B16/F10 melanoma.
AB  - One of the major drawbacks that limits the clinical application of nanoparticles
      is the lack of preliminary investigations related to their biocompatibility,
      biodegradability and biodistribution. In this work, biodegradable PEGylated
      polymer nanoparticles (NPs) have been synthesized by using macromonomers based on
      poly(epsilon-caprolaconte) oligomers. More in detail, NPs have been produced by
      adopting a surfactant-free semibatch emulsion polymerization process using PEG
      chains as a stabilizing agent. The NPs were also labeled with rhodamine B
      covalently bound to the NPs to quantitatively study their biodistribution in
      vivo. NPs were investigated in both in vitro and in vivo preclinical systems to
      study their biodistribution in mice bearing B16/F10 melanoma, as well as their
      biocompatibility and biodegradability. The NP concentration was evaluated in
      different tissues at several times after intravenous injection. The disappearance
      of the NPs from the plasma was biphasic, with distribution and elimination half
      lives of 30 min and 15 h, respectively. NPs were retained in tumors and in filter
      organs for a long time, were still detectable after 7 d and maintained a steady
      concentration in the tumor for 120 h. 48 h after injection, 70 +/- 15% of the
      inoculated NPs were excreted in the feces. The favorable tumor uptake, fast
      excretion and absence of cytotoxicity foster the further development of produced
      NPs as drug delivery carriers.

PMID- 25074672
TI  - Impact of alpha-amylase during breadmaking on in vitro kinetics of starch
      hydrolysis and glycaemic index of enriched bread with bran.
AB  - Nowadays, the use of enzymes has become a common practice in the bakery industry,
      as they can improve dough quality and texture of final product. However, the use
      of alpha-amylases could have a negative effect in the glycaemic load of product,
      due to the released sugars from the starch hydrolysis that are not used by yeasts
      during the fermentation process. This study evaluated the effect of the addition
      of alpha-amylase in bakery products with bran on in vitro kinetics of starch
      hydrolysis. The use of flour with a high degree of extraction or high bran amount
      could decrease the GI even with the inclusion of alpha-amylase in the
      formulation. It should be taken into account the amount of bran and alpha-amylase
      when formulating breads in order to obtain products with lower GI than white
      bread. However, the fact that kinetics of starch hydrolysis remained unaltered
      indicates that the use of alpha-amylase in bread-making processes could provide
      technological advantages improving quality of breads without markedly changes in
      their glycaemic index. 

PMID- 25074674
TI  - B-type natriuretic peptide-guided therapy: a systematic review.
AB  - BNP/NT-proBNP measurement has not gained widespread use for the management of
      patients with heart failure (HF) despite several randomized controlled trials. A
      systematic review addressing the question of whether patients with HF benefit
      from BNP-assisted therapy or intensified therapy compared with usual care was
      undertaken. Relevant randomized controlled trial (RCTs) were selected by
      searching Medline, Embase, AMED, Cochrane Central Register of Controlled Trials,
      Cochrane Database of Systematic Reviews, and CINAHL for English-language articles
      published from 1980 to 2012. Selected studies required patients to be treated for
      chronic HF with medical therapy based on BNP/NT-proBNP or usual care. There were
      no restrictions except that BNP/NT-proBNP measurement had to be done by an FDA
      approved method. Nine RCTs were identified with 2,104 patients with study
      duration that ranged from 3 to 18 months. Overall, there was a wide variation in
      study design and how parameters were reported including patient selection,
      baseline characteristics, therapy goals, BNP/NT-proBNP cutpoint, and outcome
      types. Meta-analysis was not appropriate given this study heterogeneity. The
      strength of evidence for the outcome of mortality, reported in seven studies, was
      found to be low due to inconsistency and imprecision. This systematic review
      showed that the evidence is of low quality and insufficient to support the use of
      BNP/NT-proBNP to guide HF therapy. Further trials with improved design are
      needed. 

PMID- 25074675
TI  - Rhodium(III)-catalyzed regioselective C-H alkenylation of phenylphosphine
      sulfides.
AB  - The regioselective alkenylation at the ortho position of phenylphosphine sulfides
      using alkenes proceeds efficiently in the presence of a cationic Cp*-rhodium(III)
      catalyst and an appropriate oxidant. A similar rhodium catalyst also promotes the
      redox-neutral coupling of the phosphine sulfides with alkynes to afford ortho
      alkenylated products. 

PMID- 25074673
TI  - Toward a clinical definition of early osteoarthritis: onset of patient-reported
      knee pain begins on stairs. Data from the osteoarthritis initiative.
AB  - OBJECTIVE: Early detection of osteoarthritis (OA) would increase the chances of
      effective intervention. We aimed to investigate which patient-reported activity
      is first associated with knee pain. We hypothesized that pain would occur first
      during activities requiring weight bearing and knee bending. METHODS: Data were
      obtained from the Osteoarthritis Initiative (OAI), a multicenter, longitudinal
      prospective observational cohort of people who have or are at high risk of OA.
      Participants completed the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC; Likert scale) annually for up to 7 years. Rasch
      analysis was used to rank the WOMAC pain questions (activities) in order of
      affirmation as the pain score increased from 0. For each total WOMAC score
      category (0-20) we selected 25 individuals at random based on their maximum score
      across all visits. Fit to the Rasch model was assessed in this subset; stability
      of question ranking over successive visits was confirmed in the full OAI.
      RESULTS: WOMAC data on 4,673 people were included, with 491 selected for subset
      analysis. The subset data showed good fit to the Rasch model (chi(2) = 43.31, P =
      0.332). In the full OAI, the "using stairs" question was the first to score
      points as the total pain score increased from 0 (baseline logit score +/- 95%
      confidence interval -4.74 +/- 0.07), then "walking" (-2.94 +/- 0.07), "standing"
      (-2.65 +/- 0.07), "lying/sitting" (-2.00 +/- 0.08), and finally "in bed" (-1.32
      +/- 0.09). This ordering was consistent over successive visits. CONCLUSION: Knee
      pain is most likely to first appear during weight-bearing activities involving
      bending of the knee, such as using stairs. First appearance of this symptom may
      identify a group suitable for early intervention strategies.

PMID- 25074676
TI  - Surveillance of hepatitis A virus in urban sewages and comparison with cases
      notified in the course of an outbreak, Italy 2013.
AB  - BACKGROUND: Over the past 20 years, Hepatitis A notifications in Italy have been
      in decline. Since the beginning of 2013 however, Italy has been experiencing a
      foodborne hepatitis A outbreak caused by genotype IA, involving hundreds of
      cases. Consumption of frozen mixed berries was deemed the potential vehicle of
      infection.We aimed to investigate the spread of hepatitis A virus (HAV) in Italy
      through the monitoring of urban sewages collected at Wastewater Treatment Plants
      (WTPs) and a subsequent comparison of environmental surveillance data with data
      from the clinical surveillance performed during the epidemic. METHODS: The study
      covered 15 months, from July 2012 to September 2013, comprising the outbreak and
      the preceding six months. Environmental surveillance consisted of the analysis of
      urban sewage samples collected at 19 WTPs in seven of the Italian regions most
      affected by the epidemic. HAV isolates were detected and typed using a nested RT
      PCR targeting the VP1/2A junction. Parallel clinical surveillance was performed
      by the sentinel surveillance system for acute viral hepatitis (SEIEVA) and by the
      ministerial Central Task Force on Hepatitis A, established with the purpose of
      determining the source of the outbreak and adopting appropriate outbreak control
      strategies. RESULTS: A total of 38/157 wastewater samples (24.2%) were positive
      for HAV, 16 collected in 2012 and 22 in 2013. Several HAV strains were detected,
      including the IA variant implicated in the outbreak and isolated from clinical
      cases over the same period. The vast majority of sequences belonged to genotype
      IB. Interestingly however, although these included variants related to strains
      that had been involved in past Italian epidemics, none were detected in recent
      clinical samples, probably due to underreporting or asymptomatic circulation.
      Conversely, a number of sequences were identified in clinical samples that were
      not found in wastewaters. CONCLUSIONS: The percentage of sewage samples detected
      as HAV-positive in this study are consistent with the classification of Italy as
      a country with low/intermediate endemicity. A combined environmental/clinical
      surveillance is able to provide a more complete picture of the spread of HAV and
      of the genotypes circulating in the population, allowing a better understanding
      of changes in disease trends.

PMID- 25074677
TI  - Heat inactivation of the Middle East respiratory syndrome coronavirus.
AB  - The culture supernatants of the emerging Middle East respiratory syndrome
      coronavirus (MERS-CoV) were submitted to three temperatures over time and tested
      for infectivity by TCID50 method on Vero E6 cells. At 56 degrees C, almost 25
      minutes were necessary to reduce the initial titre by 4 log10 . Increasing
      temperature to 65 degrees C had a strong negative effect on viral infectivity as
      virucidy dropped significantly to 1 minute. On the contrary, no significant
      decrease in titre was observed after 2 hours at 25 degrees C. These data might be
      useful in establishing biosafety measures in laboratories against MERS-CoV.

PMID- 25074678
TI  - Expression pattern of clinically relevant markers in paediatric germ cell- and
      sex-cord stromal tumours is similar to adult testicular tumours.
AB  - Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of
      childhood cancers. Like adult GCTs, they probably originate from primordial germ
      cells, but the pattern of histopathological types is different, and they occur
      predominantly in extragonadal sites along the body midline. Because they are
      rare, histology of paediatric GCTs is poorly documented, and it remains unclear
      to what extent they differ from adult GCTs. We have analysed 35 paediatric germ
      cell tumours and 5 gonadal sex-cord stromal tumours from prepubertal patients
      aged 0-15 years, to gain further knowledge, elaborate on clinical-pathological
      associations and better understand their developmental divergence. The tumours
      were screened for expression of stemness-related factors (OCT4, AP-2gamma, SOX2),
      classical yolk sac tumours (YSTs; AFP, SALL4), GCTs (HCG, PLAP, PDPN/D2-40), as
      well as markers for sex-cord stromal tumour (PDPN, GATA4). All YSTs expressed AFP
      and SALL4, with GATA4 present in 13/14. The majority of teratomas expressed SOX2
      and PDPN, whereas SALL4 was found in 8/13 immature teratomas. Adult seminoma
      markers AP-2gamma, OCT4, SALL4 and PDPN were all expressed in dysgerminoma. We
      further report a previously unrecognised pathogenetic relationship between AFP
      and SALL4 in YST in that different populations of YST cells express either SALL4
      or AFP, which suggests variable differentiation status. We also show that AP
      2gamma is expressed in the granulosa layer of ovarian follicles and weakly
      expressed in immature but not in mature granulosa cell tumours. Our findings
      indicate that the expression pattern of these antigens is similar between
      paediatric and adult GCTs, even though they develop along different developmental
      trajectories.

PMID- 25074679
TI  - Family health information sharing among older adults: reaching more family
      members.
AB  - Although family health history (FHH) information has tremendous potential in the
      prevention of common complex diseases such as heart disease and cancer, lack of
      knowledge about one's own FHH among the public hinders its utility. Older
      individuals often desire to contribute to the well-being of younger generations
      and also play critical roles in disseminating this information. This study
      evaluated psychosocial factors associated with the extent of FHH communication
      within families. Older adults (N = 110) were interviewed at three senior centers
      in an urban community. Multivariate Poisson regression analysis showed that
      respondents who received FHH from a parent reported 41 % more family members with
      whom they shared FHH (b = 0.34, p < 0.001) controlling for the family network
      size. Furthermore, one unit increase in the number of family members with whom
      respondents exchange reciprocal emotional support (b = 0.04, p < 0.01), perceived
      familiarity with own FHH (b = 0.14, p = 0.01), and self-efficacy to share FHH (b
      = 0.18, p = 0.02) were associated with 4, 15, and 20 % increases in the number of
      family members with whom respondents shared FHH, respectively. Future efforts may
      inform older adults about their important role in modeling FHH communication
      behavior to encourage information sharing in future generations while providing
      information about how to collect and disseminate FHH to increase their
      familiarity and ability to share FHH within the family. 

PMID- 25074680
TI  - Matter of margins.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer, it represents a
      significant economic burden to health services because of a large volume of
      affected patients. Surgical excision with histological assessment of the surgical
      margins is widely considered as the mainstay of BCC treatment. Incomplete
      removal, in fact, should be considered a poor prognostic indicator, as incomplete
      removal of lesions is at risk of local recurrence. Actually, dermatological
      surgeries are carried out by a variety of different types of practitioners, such
      as plastic surgeons, maxillofacial surgeons, otorhinolaryngologists,
      ophthalmologists and finally dermatologists. Incomplete removal of the tumour
      ranges from 6.3% to 25%, depending on the improper intra-operative evaluation of
      the extent of the tumour. It depends on the clinical knowledge derived from both
      training and daily experience. In this sense, the majority of the largest studies
      derive from plastic surgeons, while dermatologists have small case series, albeit
      with a higher therapeutic efficacy in terms of complete surgical excision.
      OBJECTIVES: We conducted a retrospective analysis of the surgical activity, more
      specifically we evaluated both our therapeutic accuracy and analyzed the
      prognostic factors related to incomplete excisions. METHODS: A retrospective
      review of all BCC removals was performed. A total of 4523 BCC removals were
      included; other neoplasm, benign lesions and biopsies were also excluded. Each
      BCC's size diameter, localization, histology and histological presence of
      complicating factors was assessed, then the percentage of the incomplete removal
      was calculated. RESULTS: Incomplete resections occurred in 225 (4.97%) BCCs of
      the cases. Thirteen areas were categorized into in three different levels that
      rank the risk of incomplete removals. Sub-analysis indicates that just over a
      third had no complicating factors with the lateral/deep margins. The most
      frequent complicating factor is ulceration (22.9%), while vascular invasion or
      seborrheic keratoses were not found. Actinic keratoses, scabs and scars held the
      most responsibility for the involvement of the lateral margins, while perineural
      invasion is the main factor leading to deep margin involvement. Finally, a
      different trend for the involvement of lateral or deep margins according
      different histological sub-types was highlighted; lateral involvement is more
      frequent for the infiltrative/morpheic type, while the deep margin is more
      involved in the nodular type.

PMID- 25074681
TI  - Kidney and liver transplantation in children with fibrocystic liver-kidney
      disease: data from the US Scientific Registry of Transplant Recipients: 1990
      2010.
AB  - The natural history and survival of children with fibrocystic liver-kidney
      disease undergoing solid organ transplantation have infrequently been described.
      We report outcomes in a cohort of US children with fibrocystic liver-kidney
      disease receiving solid organ transplants over 20 yr. Retrospective cohort study
      of pediatric transplant recipients with diagnoses of fibrocystic liver-kidney
      disease from 1/1990 to 3/2010, using data from the SRTR. Subjects were
      categorized by the first transplanted organ: LT, KT, or SLK. Primary outcomes
      were death, re-transplant, transplant of the alternate organ, or initiation of
      dialysis. Seven hundred and sixteen subjects were transplanted in this period.
      Median age at first transplant was 9.7 yr. Of the LT, 14 (19%) required a second
      liver transplant at median of 0.2 yr, and five (7%) required kidney transplant or
      dialysis at a median of 9.0 yr. Of the KT, 188 (31%) required a second kidney
      transplant or dialysis at a median of 5.9 yr. Twenty-nine (5%) subsequently
      received liver transplant at a median of 6.0 yr. Among patients in this registry,
      far more children underwent kidney than liver transplants. The risk of
      subsequently needing transplantation of an alternate organ was low. 

PMID- 25074682
TI  - A three-dimensional collagen construct to model lipopolysaccharide-induced
      activation of BV2 microglia.
AB  - BACKGROUND: We report a novel method of culturing microglia in three dimension
      (3D) using collagen as a substrate. By culturing microglia within a matrix, we
      aim to emulate the physical state of microglia embedded within parenchyma.
      METHODS: BV2 microglia cell suspensions were prepared with type I collagen and
      cast into culture plates. To characterise the BV2 microglia cultured in 3D, the
      cultures were evaluated for their viability, cell morphology and response to
      lipopolysaccharide (LPS) activation. Conventional monolayer cultures (grown on
      uncoated and collagen-coated polystyrene) were set up concurrently for
      comparison. RESULTS: BV2 microglia in 3D collagen matrices were viable at 48 hrs
      of culture and exhibit a ramified morphology with multiplanar cytoplasmic
      projections. Following stimulation with 1 MUg/ml LPS, microglia cultured in 3D
      collagen gels increase their expression of nitric oxide (NO) and CD40, indicating
      their capacity to become activated within the matrix. Up to 97.8% of BV2
      microglia grown in 3D cultures gained CD40 positivity in response to LPS,
      compared to approximately 60% of cells grown in a monolayer (P<.05). BV2
      microglia in 3D collagen gels also showed increased mRNA and protein expression
      of inflammatory cytokines IL-6, TNF-alpha and the chemoattractant MCP-1 following
      LPS stimulation. CONCLUSIONS: In summary, BV2 microglia cultured in 3D collagen
      hydrogels exhibit multiplanar cytoplasmic projections and undergo a
      characteristic and robust activation response to LPS. This culture system is
      accessible to a wide range of analyses and provides a useful new in vitro tool
      for research into microglial activation.

PMID- 25074683
TI  - Pregnancy outcomes of women exposed to laninamivir during pregnancy.
AB  - PURPOSE: The purpose of this study is to assess pregnancy outcomes of women
      treated with a novel neuraminidase inhibitor, laninamivir, during pregnancy.
      METHODS: A retrospective review of pregnancy outcomes of 112 pregnant women who
      were given laninamivir for treatment of influenza was performed. Possible adverse
      events, including miscarriages, preterm birth, foetal malformation and any
      neonatal morbidity requiring treatment, were assessed. RESULTS: Seventeen, 39, 46
      and 10 women were administered a single inhaled dose of 20 or 40 mg of
      laninamivir at gestational week (GW) 3-11, 12-21, 22-36 and 37 or more,
      respectively. One (1.8%) of 56 women with laninamivir at GW <22 experienced
      miscarriage at GW <12. The remaining 111 women gave birth to 111 viable infants
      but at preterm (GW <37) in nine (8.8%) of 102 women with laninamivir at GW <37.
      Three (2.7%) of the 111 newborns had malformations: forefoot varus deformity,
      foot polydactyly and cleft lip in one each born to a mother taking laninamivir at
      GW 6, 17 and 21, respectively. Five neonates (4.5%) were small for gestational
      age. Eleven (9.9%), five (4.5%) and no neonates required phototherapy for
      jaundice, transient respiratory supports for respiratory distress syndrome (n =
      2) or transient tachypnoea of the newborn (n = 3), and glucose administration for
      hypoglycaemia, respectively. CONCLUSIONS: Although this study included a small
      number of study women and no control women, the results suggested that maternal
      exposure to laninamivir did not increase the rate of adverse pregnancy and foetal
      outcomes.

PMID- 25074685
TI  - The 5th parental brain conference.

PMID- 25074686
TI  - Off-label prescriptions for atopic dermatitis in Europe.
AB  - Moderate-to-severe forms of atopic dermatitis (AD) have a substantial impact on
      the quality of life of patients and their relatives, carrying a significant
      socioeconomic burden. They often require a systemic therapy, and ciclosporine A
      (CsA) is the only medicinal product approved for this indication in a limited
      number of European countries. However, due to the safety profile of CsA and its
      approval conditions, this treatment can only be prescribed for a limited period
      of time. Thus, moderate-to-severe forms of AD represent a significant unmet
      medical need and are subject to off-label prescriptions. Besides giving some
      insights into the approval procedures for medicinal products in the European
      Union, this short review is aimed to provide some relevant background information
      for off-label prescription in AD. It also provides a clinical algorithm for the
      off-label prescription of systemic immunosuppressants in AD, discusses the
      apparent dilemma between approval and guidelines, and finally suggests practical
      rules to be considered in the context of off-label prescription. 

PMID- 25074684
TI  - Optix defines a neuroepithelial compartment in the optic lobe of the Drosophila
      brain.
AB  - BACKGROUND: During early brain development, the organisation of neural
      progenitors into a neuroepithelial sheet maintains tissue integrity during
      growth. Neuroepithelial cohesion and patterning is essential for orderly
      proliferation and neural fate specification. Neuroepithelia are regionalised by
      the expression of transcription factors and signalling molecules, resulting in
      the formation of distinct developmental, and ultimately functional, domains.
      RESULTS: We have discovered that the Six3/6 family orthologue Optix is an
      essential regulator of neuroepithelial maintenance and patterning in the
      Drosophila brain. Six3 and Six6 are required for mammalian eye and forebrain
      development, and mutations in humans are associated with severe eye and brain
      malformation. In Drosophila, Optix is expressed in a sharply defined region of
      the larval optic lobe, and its expression is reciprocal to that of the
      transcription factor Vsx1. Optix gain- and loss-of-function affects
      neuroepithelial adhesion, integrity and polarity. We find restricted cell lineage
      boundaries that correspond to transcription factor expression domains.
      CONCLUSION: We propose that the optic lobe is compartmentalised by expression of
      Optix and Vsx1. Our findings provide insight into the spatial patterning of a
      complex region of the brain, and suggest an evolutionarily conserved principle of
      visual system development.

PMID- 25074687
TI  - Mmp25beta facilitates elongation of sensory neurons during zebrafish development.
AB  - Matrix metalloproteinases (MMPs) are a large and complex family of zinc-dependent
      endoproteinases widely recognized for their roles in remodeling the extracellular
      matrix (ECM) during embryonic development, wound healing, and tissue homeostasis.
      Their misregulation is central to many pathologies, and they have therefore been
      the focus of biomedical research for decades. These proteases have also recently
      emerged as mediators of neural development and synaptic plasticity in
      vertebrates, however, understanding of the mechanistic basis of these roles and
      the molecular identities of the MMPs involved remains far from complete. We have
      identified a zebrafish orthologue of mmp25 (a.k.a. leukolysin; MT6-MMP), a
      membrane-type, furin-activated MMP associated with leukocytes and invasive
      carcinomas, but which we find is expressed by a subset of the sensory neurons
      during normal embryonic development. We detect high levels of Mmp25beta
      expression in the trigeminal, craniofacial, and posterior lateral line ganglia in
      the hindbrain, and in Rohon-Beard cells in the dorsal neural tube during the
      first 48 h of embryonic development. Knockdown of Mmp25beta expression with
      morpholino oligonucleotides results in larvae that are uncoordinated and
      insensitive to touch, and which exhibit defects in the development of sensory
      neural structures. Using in vivo zymography, we observe that Mmp25beta morphant
      embryos show reduced Type IV collagen degradation in regions of the head
      traversed by elongating axons emanating from the trigeminal ganglion, suggesting
      that Mmp25beta may play a pivotal role in mediating ECM remodeling in the
      vicinity of these elongating axons.

PMID- 25074688
TI  - OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and
      safety of fostamatinib monotherapy.
AB  - OBJECTIVES: OSKIRA-4 evaluated the efficacy of fostamatinib monotherapy versus
      placebo on the signs and symptoms of rheumatoid arthritis over 6 weeks by Disease
      Activity Score C reactive protein (DAS-28(CRP)) and assessed non-inferiority to
      adalimumab monotherapy at Week 24 by DAS-28(CRP). METHODS: Overall, 279 patients
      not currently taking disease-modifying antirheumatic drugs were randomised to:
      (A) fostamatinib 100 mg twice daily for 24 weeks plus placebo injection every 2
      weeks (PBOI); (B) fostamatinib 100 mg twice daily for 4 weeks, then 150 mg once
      daily up to Week 24, plus PBOI; (C) fostamatinib 100 mg twice daily for 4 weeks,
      then 100 mg once daily up to Week 24, plus PBOI; (D) adalimumab 40 mg every 2
      weeks for 24 weeks, plus oral placebo twice daily; or (E) oral placebo twice
      daily for 6 weeks, plus PBOI, then a switch to arm A or B. RESULTS: Fostamatinib
      demonstrated a significant improvement in DAS-28(CRP) score from baseline versus
      placebo at Week 6 for arms A and B, but not C. Fostamatinib was significantly
      less effective than adalimumab at Week 24 based on DAS-28(CRP). Adverse events
      observed with fostamatinib treatment were consistent with those reported in
      previous studies, including hypertension and diarrhoea. CONCLUSIONS: Fostamatinib
      demonstrated efficacy as monotherapy, showing superior DAS-28(CRP) score changes
      between baseline and 6 weeks when compared with placebo in treatment arms A and
      B. However, all fostamatinib regimens demonstrated inferior responses compared
      with adalimumab at Week 24. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov:
      NCT01264770.

PMID- 25074689
TI  - IL-23 expression and activation of autophagy in synovium and PBMCs of HLA-B27
      positive patients with ankylosing spondylitis. Response to: 'Evidence that
      autophagy, but not the unfolded protein response, regulates the expression of IL
      23 in the gut of patients with ankylosing spondylitis and subclinical gut
      inflammation' by Ciccia et al.

PMID- 25074690
TI  - Effect of concomitant statins on rituximab efficacy in patients with rheumatoid
      arthritis.

PMID- 25074691
TI  - MRI-detected subclinical joint inflammation is associated with radiographic
      progression.
AB  - BACKGROUND: We recently demonstrated that MRI inflammation is prevalent in
      clinically non-swollen joints of early arthritis patients. In this study, we
      assessed the relevance of this subclinical inflammation with regard to
      radiographic progression. METHODS: 1130 joints (unilateral metacarpophalangeal 2
      5, wrist and metatarsophalangeal 1-5) of 113 early arthritis patients underwent
      clinical examination and 1.5 T MRI at baseline, and radiographs at baseline and 1
      year. Two readers scored the MRIs for synovitis, bone marrow oedema (BME) and
      tenosynovitis according to Rheumatoid Arthritis (RA) Magnetic Resonance Imaging
      (MRI) Scoring System (RAMRIS). Radiographic progression over 1 year was
      determined using the Sharp-van der Heijde scoring method. RESULTS: On patient
      level, BME, synovitis and tenosynovitis were associated with radiographic
      progression, independent of known risk factors (p=0.003, 0.001 and 0.011,
      respectively). Of all non-swollen joints (n=932), 232 joints (26%) had
      subclinical inflammation (>=1 MRI-inflammation feature present). These joints
      were distributed among 91% of patients. Radiographic progression was present in
      4% of non-swollen joints with subclinical inflammation compared to 1% of non
      swollen joints without subclinical inflammation (relative risks (RR) 3.5, 95% CI
      1.3 to 9.6). Similar observations were done for BME (RR5.3, 95% CI 2.0 to 14.0),
      synovitis (RR3.4, 95% CI 1.2 to 9.3) and tenosynovitis (RR3.0, 95% CI 0.7 to
      12.7) separately. CONCLUSIONS: Radiographic progression was infrequent, but
      joints with subclinical inflammation had an increased risk of radiographic
      progression within year 1. This demonstrates the relevance of MRI-detected
      subclinical inflammation.

PMID- 25074692
TI  - Severity of injuries in different modes of transport, expressed with disability
      adjusted life years (DALYs).
AB  - BACKGROUND: Health impact assessment (HIA) studies are increasingly predicting
      the health effects of mode shifts in traffic. The challenge for such studies is
      to combine the health effects, caused by injuries, with the disease driven health
      effects, and to express the change in the health with a common health indicator.
      Disability-adjusted life year (DALY) combines years lived disabled or injured
      (YLD) and years of life lost (YLL) providing practical indicator to combine
      injuries with diseases. In this study, we estimate the average YLDs for one
      person injured in a transport crash to allow easy to use methods to predict
      health effects of transport injuries. METHODS: We calculated YLDs and YLLs for
      transport fatalities and injuries based on the data from the Swedish Traffic
      Accident Data Acquisition (STRADA). In STRADA, all the fatalities and most of the
      injuries in Sweden for 2007-2011 were recorded. The type of injury was recorded
      with the Abbreviated Injury Scale (AIS) codes. In this study these AIS codes were
      aggregated to injury types, and YLDs were calculated for each victim by
      multiplying the type of injury with the disability weight and the average
      duration of that injury. YLLs were calculated by multiplying the age of the
      victim with life expectancy of that age and gender. YLDs and YLLs were estimated
      separately for different gender, mode of transport and location of the crash.
      RESULTS: The average YLDs for injured person was 14.7 for lifelong injuries and
      0.012 for temporal injuries. The average YLDs per injured person for lifelong
      injuries for pedestrians, cyclists and car occupants were 9.4, 12.8 and 18.4,
      YLDs, respectively. Lifelong injuries sustained in rural areas were on average
      31% more serious than injuries in urban areas. CONCLUSIONS: The results show that
      shifting modes of transport will not only change the likelihood of injuries but
      also the severity of injuries sustained, if injured. The results of this study
      can be used to predict DALY changes in HIA studies that take into account mode
      shifts between different transport modes, and in other studies predicting the
      health effects of traffic injuries.

PMID- 25074693
TI  - Does an energy drink cause a transient ischemic attack?
AB  - Energy drinks have become a popular beverage especially among young individuals.
      The growing literature sheds light on acute health problems associated with these
      products, although they have not yet been in existence long enough to build a
      solid, evidence-based appreciation of potential long-term effects. Perhaps the
      greatest concern about energy drinks is the amount of caffeine they contain,
      which generally far exceeds that in other beverages. A transient ischemic attack
      (TIA) has been traditionally defined as an episode of neurologic dysfunction
      caused by focal cerebral ischemia with complete recovery within 24 hours. We
      report a patient who had a TIA after intake of an energy drink without alcohol.
      To the best of our knowledge, the following case is the first report of TIA after
      intake of an energy drink.

PMID- 25074694
TI  - Thrombolysis after initially unsuccessful cardiopulmonary resuscitation in
      presumed pulmonary embolism.
AB  - The life-saving administration of thrombolytic therapy after initially
      unsuccessful cardiopulmonary resuscitation (CPR) in 7 patients with presumed
      pulmonary embolism (PE) was reported. Seven patients who had cardiac arrest were
      admitted to our emergency department. The clinical diagnosis of all these
      patients was highly suspected with PE; therefore, 50 mg recombinant tissue
      plasminogen activator with 50-mL dilution was administered in a 15-minute period
      after initially unsuccessful CPR. Of 7 patients, 5 (71.4%) achieved return of
      spontaneous circulation after CPR and thrombolytic therapy, and 3 (42.9%) of 7
      patients were discharged alive through successive treatments. A 90-day follow-up
      showed that 2 patients were neurologically intact, and 1 patient was mildly
      disabled. These results demonstrate that thrombolysis after initially
      unsuccessful CPR in presumed PE may have beneficial effects.

PMID- 25074695
TI  - Non-ST-elevation myocardial infarction in the United States: contemporary trends
      in incidence, utilization of the early invasive strategy, and in-hospital
      outcomes.
AB  - BACKGROUND: There has been a paradigm shift in the definition of timing of early
      invasive strategy (EIS) for patients admitted with non-ST-elevation myocardial
      infarction (NSTEMI) in the last decade. Data on trends of EIS for NSTEMI and
      associated in-hospital outcomes are limited. Our aim is to analyze temporal
      trends in the incidence, utilization of early invasive strategy, and in-hospital
      outcomes of NSTEMI in the United States. METHODS AND RESULTS: We analyzed the
      2002-2011 Nationwide Inpatient Sample databases to identify all patients >=40
      years of age with the principal diagnosis of acute myocardial infarction (AMI)
      and NSTEMI. Logistic regression was used for overall, age-, sex-, and
      race/ethnicity-stratified trend analysis. From 2002 to 2011, we identified 6 512
      372 patients with AMI. Of these, 3 981 119 (61.1%) had NSTEMI. The proportion of
      patients with NSTEMI increased from 52.8% in 2002 to 68.6% in 2011 (adjusted odds
      ratio [OR; per year], 1.055; 95% confidence interval [CI], 1.054 to 1.056) in the
      overall cohort. Similar trends were observed in age-, sex-, and race/ethnicity
      stratified groups. From 2002 to 2011, utilization of EIS at day 0 increased from
      14.9% to 21.8% (Ptrend<0.001) and utilization of EIS at day 0 or 1 increased from
      27.8% to 41.4% (Ptrend<0.001). Risk-adjusted in-hospital mortality in the overall
      cohort decreased during the study period (adjusted OR [per year], 0.976; 95% CI,
      0.974 to 0.978). CONCLUSIONS: There have been temporal increases in the
      proportion of NSTEMI and, consistent with guidelines, greater utilization of EIS.
      This has been accompanied by temporal decreases in in-hospital mortality and
      length of stay.

PMID- 25074696
TI  - Health-related quality of life in premature acute coronary syndrome: does patient
      sex or gender really matter?
AB  - BACKGROUND: Limited data exist as to the relative contribution of sex and gender
      on health-related quality of life (HRQL) among patients with acute coronary
      syndrome (ACS). This study aims to evaluate the effect of sex and gender-related
      variables on long-term HRQL among young adults with ACS. METHODS AND RESULTS:
      GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench
      to beyond-Premature Acute Coronary SYndrome) is a multicenter, prospective cohort
      study (January 2009 to August 2013) of adults aged 18 to 55 years, hospitalized
      with ACS. HRQL was measured at baseline, 1, 6, and 12 months using the Short Form
      12 and Seattle Angina Questionnaire (SAQ) among 1213 patients. Median age was 49
      years. Women reported worse HRQL than men over time post-ACS, both in terms of
      physical and mental functioning. Gender-related factors were more likely to be
      predictors of HRQL than sex. Femininity score, social support, and housework
      responsibility were the most common gender-related predictors of HRQL at 12
      months. We observed an interaction between female sex and social support
      (beta=0.44 [95% confidence interval, 0.01, 0.88]; P=0.047) for the physical
      limitation subscale of the SAQ. CONCLUSIONS: Young women with ACS report
      significantly poorer HRQL than young men. Gender appears to be more important
      than sex in predicting long-term HRQL post-ACS. Specific gender-related factors,
      such as social support, may be amenable to interventions and could improve the
      HRQL of patients with premature ACS.

PMID- 25074701
TI  - Effects of pistachio by-products on digestibility, milk production, milk fatty
      acid profile and blood metabolites in Saanen dairy goats.
AB  - The objective of this study was to investigate the effects of pistachio by
      products (PBP) on nutrient digestibility, blood metabolites and milk fatty acid
      (FA) profile in Saanen dairy goats. Nine multiparous lactating Saanen goats (on
      day 90 post-partum, 45 +/- 2/kg BW) were randomly assigned to a 3 * 3 Latin
      square design with three treatment diets: 1) control diet (alfalfa hay based), 2)
      32% PBP and 3) 32% PBP + polyethylene glycol (PEG-4000; 1 g/kg dry matter). Each
      period lasted 21 days, including 14 day for treatment adaptation and 7 day for
      data collection. Pistachio by-products significantly decreased (p < 0.01) crude
      protein (CP) digestibility compared with the control diet (64.4% vs. 58.7%), but
      PEG addition did not differ for CP digestibility of goats fed 32% PBP + PEG and
      those fed the two other diets. The digestibility of NDF tended (p = 0.06) to
      decrease for goats fed PBP compared with those fed the control diet. Yields of
      milk and 4% fat-corrected milk were not affected by dietary treatments. Compared
      with the control diet, PBP supplementation appreciably changed the proportions of
      almost all the milk FA measured; the main effects were decreases (p < 0.01) in FA
      from 8:0 to 16:0 and increases (p < 0.01) proportions of cis-9, trans-11 18:2 and
      trans-11 18:1, monounsaturated FA, polyunsaturated FA and long-chain FA. The
      saturated FA, short-chain FA and medium-chain FA proportions were lower (p <
      0.01) in goats fed the two PBP supplemented diet than in those fed the control
      diet and PEG addition led to intermediate proportions of saturated FA,
      unsaturated and monounsaturated FA. Inclusion of PBP in the diet decreased (p <
      0.01) plasma concentrations of glucose and urea nitrogen compared with the
      control diet. It was concluded that PBP can be used as forage in the diet of
      dairy goats without interfering with milk yield. Inclusion of 32% PBP in the diet
      of dairy goats had beneficial effects on milk FA profile but PEG addition to PBP
      did not contribute to enhance further milk FA profile. 

PMID- 25074698
TI  - Remote ischemic preconditioning in children undergoing cardiac surgery with
      cardiopulmonary bypass: a single-center double-blinded randomized trial.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) harnesses an innate defensive
      mechanism that protects against inflammatory activation and ischemia-reperfusion
      injury, known sequelae of cardiac surgery with cardiopulmonary bypass. We sought
      to determine the impact of RIPC on clinical outcomes and physiological markers
      related to ischemia-reperfusion injury and inflammatory activation after cardiac
      surgery in children. METHODS AND RESULTS: Overall, 299 children (aged neonate to
      17 years) were randomized to receive an RIPC stimulus (inflation of a blood
      pressure cuff on the left thigh to 15 mm Hg above systolic for four 5-minute
      intervals) versus a blinded sham stimulus during induction with a standardized
      anesthesia protocol. Primary outcome was duration of postoperative hospital stay,
      with serial clinical and laboratory measurements for the first 48 postoperative
      hours and clinical follow-up to discharge. There were no significant baseline
      differences between RIPC (n=148) and sham (n=151). There were no in-hospital
      deaths. No significant difference in length of postoperative hospital stay was
      noted (sham 5.4 versus RIPC 5.6 days; difference +0.2; adjusted P=0.91), with the
      95% confidence interval (-0.7 to +0.9) excluding a prespecified minimal
      clinically significant differences of 1 or 1.5 days. There were few significant
      differences in other clinical outcomes or values at time points or trends in
      physiological markers. Benefit was not observed in specific subgroups when
      explored through interactions with categories of age, sex, surgery type,
      Aristotle score, or first versus second half of recruitment. Adverse events were
      similar (sham 5%, RIPC 6%; P=0.68). CONCLUSIONS: RIPC is not associated with
      important improvements in clinical outcomes and physiological markers after
      cardiac surgery in children. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov.
      Unique identifier: NCT00650507.

PMID- 25074699
TI  - Electrocardiographic repolarization-related variables as predictors of coronary
      heart disease death in the women's health initiative study.
AB  - BACKGROUND: We evaluated 25 repolarization-related ECG variables for the risk of
      coronary heart disease (CHD) death in 52 994 postmenopausal women from the
      Women's Health Initiative study. METHODS AND RESULTS: Hazard ratios from Cox
      regression were computed for subgroups of women with and without cardiovascular
      disease (CVD). During the average follow-up of 16.9 years, 941 CHD deaths
      occurred. Based on electrophysiological considerations, 2 sets of ECG variables
      with low correlations were considered as candidates for independent predictors of
      CHD death: Set 1, ?(Tp|Tref), the spatial angle between T peak (Tp) and normal T
      reference (Tref) vectors; ?(Tinit|Tterm), the angle between the initial and
      terminal T vectors; STJ depression in V6 and rate-adjusted QTp interval (QTpa);
      and Set 2, TaVR and TV1 amplitudes, heart rate, and QRS duration. Strong
      independent predictors with over 2-fold increased risk for CHD death in women
      with and without CVD were ?(Tp|Tref) >42 degrees  from Set 1 and TaVR amplitude >
      100 MUV from Set 2. The risk for these CHD death predictors remained significant
      after multivariable adjustment for demographic/clinical factors. Other
      significant predictors for CHD death in fully adjusted risk models were
      ?(Tinit|Tterm) >30 degrees , TV1 >175 MUV, and QRS duration >100 ms. CONCLUSIONS:
      ?(Tp|Tref) angle and TaVR amplitude are associated with CHD mortality in
      postmenopausal women. The use of these measures to identify high-risk women for
      further diagnostic evaluation or more intense preventive intervention warrants
      further study. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00000611.

PMID- 25074702
TI  - Evaluation of antioxidant and antiproliferative activity of Flueggea leucopyrus
      Willd (katupila).
AB  - BACKGROUND: Flueggea leucopyrus Willd is a shrub grown in many parts of the dry
      zones in Sri Lanka. The leaves of F. leucopyrus has been used for treating cancer
      in the traditional system of medicine in Sri Lanka. Hence, this study was
      performed to analyze the antioxidant and antiproliferative properties of the
      aqueous extract of the leaves of F. leucopyrus on HEp-2 cells. METHOD: The
      aqueous extract of F. leucopyrus leaves (AEFLL) was freeze dried. Total phenolic
      content was assayed using Folin Ciocalteu reagent. Antioxidant activities of the
      extracts were evaluated using in vitro assays: inhibition of DPPH (1,1-diphenyl-2
      picrylhydrazyl) radical scavenging and 2-deoxy-D-ribose degradation assay. Nitric
      oxide radical scavenging activity was determined by using Griess reagent. The
      MTT, LDH assays and protein synthesis were used to study antiproliferative and
      cytotoxic activities against the Hep-2 cell after 24 hour exposure. DNA
      fragmentation and microscopic examination of cells stained with a mixture of
      ethidium bromide/acridine orange were used to visualize apoptosis in HEp-2 cells
      treated with the AEFLL. RESULTS: The total phenolic content of the extract was
      22.15 +/- 1.65 (w/w) % of gallic acid equivalent. The values for EC50 were 11.16
      +/- 0.37, 4.82 +/- 1.82 and 23.77 +/- 3.16 MUg/mL for DPPH radical scavenging,
      nitric oxide radical scavenging activity and 2-deoxy-D-ribose degradation assay
      respectively. The EC50 with MTT and LDH assays were 506.8 +/- 63.16 and 254.52 +/
      42.92 MUg/mL respectively. A dose dependent decrease in protein synthesis in HEp
      2 cells was shown with an EC50 value of 305.84 +/- 12.40 MUg/mL. DNA
      fragmentation and ethidium bromide/acridine assays showed that the AEFLL induces
      apoptosis in HEp-2 cells. These results were in conformity with the morphological
      changes observed in the cells treated with the AEFLL. The brine shrimp bioassay
      showed that the AEFLL had no lethality over the concentration range of 50-500
      MUg/mL. CONCLUSIONS: Aqueous extract of the leaves of F. leucopyrus extract
      demonstrated antioxidant activity in vitro. Further it showed antiproliferative
      properties and induced apoptosis in HEp-2 cells.

PMID- 25074703
TI  - Neurodegenerative disease: propagating pathology.

PMID- 25074704
TI  - Dr. Erla K. Svavarsdottir: Honorary Scientist Award 2014.

PMID- 25074705
TI  - Survival of Australian lung cancer patients and the impact of distance from and
      attendance at a thoracic specialist centre: a data linkage study.
AB  - BACKGROUND: Lung cancer patients have better survival when treated in thoracic
      surgical (specialist) centres. AIMS: To determine whether outcome of non-small
      cell lung cancer (NSCLC) patients is poorer with increasing distance to the
      nearest accessible specialist hospital (NASH). METHODS: We linked cancer
      registry, hospital and death records of 23,871 NSCLC patients; 3240 localised,
      2435 regional and 3540 distant stage patients hospitalised within 12 months of
      diagnosis were analysed. Distance from patients' residences to the NASH was
      measured using geographical coordinates. Cox proportional hazards models examined
      predictors of NSCLC death. RESULTS: Having a resection of the cancer, which
      admission to a specialist hospital made more likely, substantially reduced hazard
      of NSCLC death. Distance influenced hazard of death through both these variables;
      a patient was less likely to be admitted to a specialist hospital than a general
      hospital and less likely to have a resection the further they lived from the
      NASH. However, patients who lived distant from the NASH and were admitted to a
      specialist hospital were more likely to have a resection and less likely to die
      from NSCLC than patients admitted to a specialist hospital and living closer to
      the NASH. These patterns varied little with lung cancer stage. CONCLUSIONS: NSCLC
      outcome is best when patients are treated in a specialist hospital. Greater
      distance to the NASH can affect its outcome by reducing the likelihood of being
      treated in a specialist hospital. Research is needed into patient and health
      service barriers to referral of NSCLC patients for specialist care.

PMID- 25074706
TI  - IL-27 controls sepsis-induced impairment of lung antibacterial host defence.
AB  - BACKGROUND: Interleukin 27 (IL-27) is an important cytokine regulating host
      immune responses. However, its role in sepsis-induced immunosuppression remains
      unclear. AIM: To investigate the role of IL-27 in modulating sepsis-induced
      immunosuppression using a murine model of caecal ligation and puncture (CLP)
      induced sepsis followed by secondary challenge with Pseudomonas aeruginosa.
      METHODS: CLP or sham surgery was performed in wild-type (WT) and IL-27 receptor
      (IL-27R)/WSX-1 knockout (KO) mice, and then mice were infected with intratracheal
      P aeruginosa. RESULTS: IL-27 was upregulated in patients with sepsis and septic
      mice. Following sepsis and secondary intrapulmonary bacterial challenge, IL-27R
      KO mice had higher survival rates and improved bacterial clearance from lung and
      blood compared with WT mice, which was associated with early increased pulmonary
      cytokine/chemokine production, as well as enhanced neutrophil recruitment to
      airspaces. Neutralisation of IL-27 in septic mice significantly improved survival
      and clearance of bacteria from the lungs of septic mice infected with P
      aeruginosa, and direct application of recombinant IL-27 could increase
      susceptibility to P aeruginosa infection. The resistance of septic IL-27R KO mice
      to secondary P aeruginosa infection was abrogated by depletion of alveolar
      macrophages (AMs) and neutrophils. AMs from septic IL-27R KO mice had higher
      bacterial uptake and killing capacities, enhanced cytokine/chemokine production,
      and increased expression of costimulatory molecules compared with those from WT
      mice, while neutrophils from septic IL-27R KO mice had increased bacterial
      killing ability and higher expression of adhesion molecule Mac-1 compared with WT
      neutrophils. CONCLUSIONS: IL-27 is an important mediator of sepsis-induced
      impairment of lung antibacterial host defence.

PMID- 25074707
TI  - Nanopore back titration analysis of dipicolinic acid.
AB  - Here, we report a novel label-free nanopore back titration method for the
      detection of dipicolinic acid, a marker molecule for bacterial spores. By
      competitive binding of the target analyte and a large ligand probe to metal ions,
      dipicolinic acid could be sensitively and selectively detected. This nanopore
      back titration approach should find useful applications in the detection of other
      species of medical, biological, or environmental importance if their direct
      detection is difficult to achieve. 

PMID- 25074708
TI  - [Sitosterolemia in a 2 year-old child with xanthomas and hematological
      anomalies].

PMID- 25074709
TI  - [Underwater delivery. Consensus of the Spanish Neonatology Society and the
      Perinatal Section of the Spanish Obstetrics and Gynecology Society].
AB  - Immersion in water during labor and delivery as an alternative to traditional
      delivery is a practice that has increased in many countries. This technique is
      effective in reducing pain and duration of labor. The American Academy of
      Pediatrics and The American College of Obstetricians and Gynecologists have
      published a clinical report which indicates the potential maternal benefits
      during the first stage of labor but, questions the performance of this technique
      during delivery and birth of the newborn. In this report, the Spanish Society of
      Neonatology and the Spanish Society of Obstetrics and Gynecology analyze the
      current scientific evidence on water immersion delivery, and the impact this
      practice could have in the mother and especially in the wellbeing of newborn.

PMID- 25074710
TI  - Strong thermo-induced single and two-photon green luminescence in self-organized
      peptide microtubes.
AB  - Diphenylalanine peptide nano- and microtubes formed by self-assembly demonstrate
      strongly enhanced and tunable single-photon and two-photon luminescence in the
      visible range, which appears after heat- or laser treatment of these self
      organized peptide microtubes. This process significantly extends the
      functionality of these microstructures and can trigger a new interest in the
      optical properties of structures based on short peptides. 

PMID- 25074711
TI  - Measuring change in relating and interrelating during the early stages of
      psychotherapy: Comparison with a nonpatients' sample.
AB  - The study examined whether the relative short time period of two months of
      individual psychotherapy improved patients' psychiatric symptoms, their negative
      relating (i.e., destructive and undesirable interpersonal attitudes and behavior
      to others) and their negative interrelating (i.e., destructive and undesirable
      relationship with their partners). A sample of 60 outpatients, reportedly
      suffering mainly from a mood or anxiety disorder, were compared with a sample of
      48 nonpatients and their partners, over a comparable time span. It was shown that
      the patients' psychopathology scores dropped significantly. Significant changes
      in some relating and interrelating scores also occurred, even though the therapy
      had not specifically addressed these issues. Unexpectedly, the partners
      demonstrated some degree of deterioration both in their relating and their
      interrelating scores.

PMID- 25074712
TI  - Whole-genome bisulfite sequencing of multiple individuals reveals complementary
      roles of promoter and gene body methylation in transcriptional regulation.
AB  - BACKGROUND: DNA methylation is an important type of epigenetic modification
      involved in gene regulation. Although strong DNA methylation at promoters is
      widely recognized to be associated with transcriptional repression, many aspects
      of DNA methylation remain not fully understood, including the quantitative
      relationships between DNA methylation and expression levels, and the individual
      roles of promoter and gene body methylation. RESULTS: Here we present an
      integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data
      from human samples and cell lines. We find that while promoter methylation
      inversely correlates with gene expression as generally observed, the repressive
      effect is clear only on genes with a very high DNA methylation level. By means of
      statistical modeling, we find that DNA methylation is indicative of the
      expression class of a gene in general, but gene body methylation is a better
      indicator than promoter methylation. These findings are general in that a model
      constructed from a sample or cell line could accurately fit the unseen data from
      another. We further find that promoter and gene body methylation have minimal
      redundancy, and either one is sufficient to signify low expression. Finally, we
      obtain increased modeling power by integrating histone modification data with the
      DNA methylation data, showing that neither type of information fully subsumes the
      other. CONCLUSION: Our results suggest that DNA methylation outside promoters
      also plays critical roles in gene regulation. Future studies on gene regulatory
      mechanisms and disease-associated differential methylation should pay more
      attention to DNA methylation at gene bodies and other non-promoter regions.

PMID- 25074713
TI  - Dermal scarification versus intramuscular diclofenac sodium injection for the
      treatment of renal colic: a prospective randomized clinical trial.
AB  - The aim of the study is to determine whether dermal scarification is equally
      effective for treating acute renal colic compared to diclofenac sodium
      intramuscular therapy. A prospective, randomized controlled study was conducted
      with methodologic rigor based on CONSORT criteria. A total of 291 patients, aged
      >= 18 years, suffering from acute renal colic were included in this trial and
      randomly assigned in two groups. Patients in the first group (A) received
      endodermal injection (dermal scarification) of 1 ml normal saline at the area of
      intensity of pain. The second group (B) received 75 mg diclofenac sodium by
      intramuscular injection. The success of each method defined the primary end
      point. Pain intensity before and after treatment was assessed using a visual
      analog scale. The time onset and the duration of analgesia were also recorded.
      There was no significant difference between the two groups regarding hematuria (p
      = 0.158), stone identification at KUB (p = 0.751) and mean pain intensity (p =
      0.609) before treatment initiation. The method was successful in 75.5 % of
      patients in group A and 74.3 % of patients in group B (p = 0.812). Mean pain
      reduction was comparable, 5.65 +/- 3.05 in group A and 5.34 +/- 2.99 in group B
      (p = 0.379), with dermal scarification eliciting its effect considerably faster,
      whereas the duration of analgesia was longer in the diclofenac group (p < 0.05).
      In conclusion, dermal scarification could constitute an alternative method for
      treating renal colic as it is equally effective compared to the standard
      treatment of diclofenac sodium.

PMID- 25074714
TI  - Does percutaneous nephrolithotomy and its outcomes have an impact on renal
      function? Quantitative analysis using SPECT-CT DMSA.
AB  - To assess the functional effects of percutaneous nephrolithotomy (PCNL) and its
      outcomes in the operated kidney, we prospectively studied 30 consecutive cases
      undergoing PCNL. Kidney function was evaluated preoperatively and 3 months after
      surgery with serum creatinine, glomerular filtration rate (GFR), and with (99m)Tc
      DMSA SPECT-CT scans to determine the differential renal function (DRF). PCNL
      effects in the operated kidney DRF were considered globally (DRFPLANAR, DRFSPECT)
      and in the region of percutaneous access (DRFACCESS). PCNL functional impact was
      also assessed depending on its outcomes, namely success (stone-free status) and
      the development of perioperative complications. PCNL has rendered 73 % of the
      cases completely stone free with a 33 % complication rate. After PCNL, serum
      creatinine and GFR did not change significantly, whereas DRFPLANAR and DRFSPECT
      dropped 1.2 % (p = 0.014) and 1.0 % (p = 0.041), respectively. The highest
      decrease was observed in DRFACCESS (1.8 %, p = 0.012). Stone-free status after
      PCNL did not show any impact on kidney function. Conversely, cases that suffered
      from a complication showed impairment in serum creatinine (0.1 mg/dL, p = 0.028),
      in GFR (11.1 mL/min, p = 0.036) as well as in DRFPLANAR (2.7 %, p = 0.018),
      DRFSPECT (2.2 %, p = 0.023) and DRFACCESS (2.7 %, p = 0.049). We conclude that
      PCNL has a minimal impact on global kidney function, which is mainly located in
      the region of percutaneous access. The advent of perioperative complications
      increased PCNL functional damage, whereas the stone-free status did not show any
      meaningful effect.

PMID- 25074715
TI  - Postmortem dynamic cerebral angiography for detecting aneurysm and bleeding sites
      in cases of subarachnoid hemorrhage.
AB  - One of the advantages of postmortem imaging is its ability to obtain diagnostic
      findings in a non-destructive manner when autopsy is either difficult or may
      destroy forensic evidence. In recent years, efforts have been made to incorporate
      computed tomography (CT) based postmortem angiography into forensic pathology;
      however, it is not currently clear how well the modality can determine sites of
      bleeding in cases of subarachnoid hemorrhage. Therefore, in this study, we
      investigated the utility of postmortem cerebral angiography using multi-detector
      row CT (MDCT) by injecting a contrast medium through a catheter inserted into the
      internal carotid and vertebral arteries of 10 subarachnoid hemorrhage cases.
      While postmortem MDCT angiography (PMCTA) was capable of detecting aneurysms in a
      non-destructive manner, it was sometimes difficult to identify the aneurysm and
      bleeding sites because of a large amount of contrast medium leaking into the
      extravascular space. To overcome this problem, we developed the novel contrast
      imaging method "dynamic cerebral angiography," which involves scanning the same
      area multiple times while injecting contrast medium to enable real-time
      observation of the contrasted vasculature. Using multiphase contrast images
      acquired by this method, we successfully captured the moment when contrast medium
      leaked from the hemorrhage site. This method will be useful for identifying exact
      bleeding sites on PMCTA. 

PMID- 25074716
TI  - Mass, energy and material balances of SRF production process. Part 2: SRF
      produced from construction and demolition waste.
AB  - In this work, the fraction of construction and demolition waste (C&D waste)
      complicated and economically not feasible to sort out for recycling purposes is
      used to produce solid recovered fuel (SRF) through mechanical treatment (MT). The
      paper presents the mass, energy and material balances of this SRF production
      process. All the process streams (input and output) produced in MT waste sorting
      plant to produce SRF from C&D waste are sampled and treated according to CEN
      standard methods for SRF. Proximate and ultimate analysis of these streams is
      performed and their composition is determined. Based on this analysis and
      composition of process streams their mass, energy and material balances are
      established for SRF production process. By mass balance means the overall mass
      flow of input waste material stream in the various output streams and material
      balances mean the mass flow of components of input waste material stream (such as
      paper and cardboard, wood, plastic (soft), plastic (hard), textile and rubber) in
      the various output streams of SRF production process. The results from mass
      balance of SRF production process showed that of the total input C&D waste
      material to MT waste sorting plant, 44% was recovered in the form of SRF, 5% as
      ferrous metal, 1% as non-ferrous metal, and 28% was sorted out as fine fraction,
      18% as reject material and 4% as heavy fraction. The energy balance of this SRF
      production process showed that of the total input energy content of C&D waste
      material to MT waste sorting plant, 74% was recovered in the form of SRF, 16%
      belonged to the reject material and rest 10% belonged to the streams of fine
      fraction and heavy fraction. From the material balances of this process, mass
      fractions of plastic (soft), paper and cardboard, wood and plastic (hard)
      recovered in the SRF stream were 84%, 82%, 72% and 68% respectively of their
      input masses to MT plant. A high mass fraction of plastic (PVC) and rubber
      material was found in the reject material stream. Streams of heavy fraction and
      fine fraction mainly contained non-combustible material (such as stone/rock, sand
      particles and gypsum material). 

PMID- 25074717
TI  - Using liquid waste streams as the moisture source during the hydrothermal
      carbonization of municipal solid wastes.
AB  - Hydrothermal carbonization (HTC) is a thermal conversion process that can be an
      environmentally beneficial approach for the conversion of municipal solid wastes
      to value-added products. The influence of using activated sludge and landfill
      leachate as initial moisture sources during the carbonization of paper, food
      waste and yard waste over time at 250 degrees C was evaluated. Results from batch
      experiments indicate that the use of activated sludge and landfill leachate are
      acceptable alternative supplemental liquid sources, ultimately imparting minimal
      impact on carbonization product characteristics and yields. Regression results
      indicate that the initial carbon content of the feedstock is more influential
      than any of the characteristics of the initial liquid source and is statistically
      significant when describing the relationship associated with all evaluated
      carbonization products. Initial liquid-phase characteristics are only
      statistically significant when describing the solids energy content and the mass
      of carbon in the gas-phase. The use of these alternative liquid sources has the
      potential to greatly increase the sustainability of the carbonization process. A
      life cycle assessment is required to quantify the benefits associated with using
      these alternative liquid sources. 

PMID- 25074718
TI  - Prevalence and regional disparities in abdominal obesity among children and
      adolescents in Shandong, China, surveyed in 2010.
AB  - BACKGROUND/AIMS: A rising prevalence of childhood obesity (assessed by body mass
      index) has been observed in China. However, there are very few published data on
      abdominal obesity among children and adolescents. The present study examined the
      prevalence and regional disparities in abdominal obesity among children and
      adolescents in Shandong, China. METHODS: Data for this study were obtained from a
      large cross-sectional survey. A total of 42,296 students (21,218 boys and 21,078
      girls) aged 7-18 years from 16 districts participated in this study. Height and
      waist circumference (WC) of all subjects were measured; waist-to-height ratio
      (WHtR) was calculated from their height and WC. Abdominal obesity was defined as
      WHtR >=0.5. All subjects were stratified by gender, age and the area of
      residence, and abdominal obesity frequencies were compared among different
      groups. RESULTS: Substantial regional, socioeconomic and urban/rural disparities
      exist in child and adolescent abdominal obesity. The overall prevalences of
      abdominal obesity among different groups of children and adolescents aged 7-18
      years were 19.92% (urban boys), 11.94% (rural boys), 8.43% (urban girls) and
      5.85% (rural girls). The prevalence of abdominal obesity varied from 24.98% in
      high-socioeconomic status (SES) urban boys to 4.58% in low-SES rural girls.
      Subjects living in coastal and high-urbanization districts had a higher
      prevalence of abdominal obesity than those living in inland and low-urbanization
      districts. CONCLUSIONS: Abdominal obesity among children and adolescents in China
      is associated with affluence and urban residence. Interventions and strategies to
      combat obesity should be based on this specific context, targeting high-SES urban
      areas.

PMID- 25074719
TI  - Diffusion-weighted MRI as a potential imaging biomarker reflecting the metastatic
      potential of upper urinary tract cancer.
AB  - OBJECTIVE: To evaluate the role of diffusion-weighted MRI (DW-MRI) as an imaging
      biomarker for upper urinary tract cancer (UUTC) that has already metastasized or
      will metastasize soon. METHODS: 61 patients clinically diagnosed with UUTC were
      prospectively enrolled in this study. All the patients underwent MRI, including
      DW-MRI, prior to any interventions. Correlations between apparent diffusion
      coefficient (ADC) and other clinicopathological variables, including metastasis
      free survival, were analysed. RESULTS: Median follow-up period was 938 days. Of
      the 61 patients, 12 had any metastases at the initial diagnosis. 11 patients
      developed metastases during the follow-up period. These 23 patients were
      categorized as "Metastatic". Of the remaining 38 patients, 35 with a follow-up
      period longer than 400 days were categorized as "Localized". ADC was
      significantly lower in the Metastatic category than in the Localized (p = 0.0002)
      category. Multivariate analysis of pre-operative variables identified ADC (cut
      off value, 1.08 * 10(-3) mm(2) s(-1)) and clinical T stage based on T2 weighted
      MRI as an independent predictive factor of metastatic UUTC. 46 patients without
      any metastases during the initial diagnosis were stratified into a high-risk
      group (16 patients with low ADC and clinical T3-4) and a low-risk group (30
      patients with high ADC or clinical Ta-2). The 3-year metastasis-free survivals
      were 45% and 93%, respectively. CONCLUSION: In the current study, UUTC with lower
      ADC value is more likely to have metastatic potential. Incorporating ADC with
      clinical T stage helps to differentiate metastatic UUTC at the initial diagnosis.
      ADVANCES IN KNOWLEDGE: DW-MRI is a potential imaging biomarker reflecting
      metastatic propensity of UUTC.

PMID- 25074720
TI  - Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA
      rituximab with 90Y and 111In for domestic radioimmunotherapy and
      radioscintigraphy of non-Hodgkin's lymphoma.
AB  - BACKGROUND: On the basis of results of our previous investigations on 90Y-DTPA
      rituximab and in order to fulfil national demands to radioimmunoconjugates for
      radioscintigraphy and radioimmunotherapy of Non-Hodgkin's Lymphoma (NHL),
      preparation and radiolabeling of a lyophilized formulation (kit) of DOTA
      rituximab with 111In and 90Y was investigated. METHODS: 111In and 90Y with high
      radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear
      reaction and a locally developed 90Sr/90Y generator, respectively. DOTA-rituximab
      immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and
      rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of
      conjugates were determined by transchelation reaction between DOTA and arsenaso
      yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with 111In and
      90Y and radioimmunoconjugates were checked for radiochemical purity by
      chromatography methods and for immunoreactivity by cell-binding assay using Raji
      cell line. The stability of radiolabeled conjugate with the approximate number of
      7 DOTA molecules per one rituximab molecule which was prepared in moderate yield
      and showed moderate immunoreactivity, compared to two other prepared
      radioimmunoconjugates, was determined at different time intervals and against
      EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide
      gel electrophoresis, respectively. The biodistribution of the selected
      radioimmunoconjugate in rats was determined by measurement of the radioactivity
      of different organs after sacrificing the animals by ether asphyxiation. RESULTS:
      The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed
      stability after 24 h at room temperature, after 96 h at 4 degrees C, as the
      lyophilized formulation after six months storage and against EDTA and human
      serum. This radioimmunoconjugate had a biodistribution profile similar to that of
      90Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL, and
      showed low brain and lung uptakes and low yttrium deposition into bone.
      CONCLUSION: Findings of this study suggest that further investigations may result
      in a lyophilized (kit) formulation of DOTA-rituximab which could be easily
      radiolabeled with 90Y and 111In in order to be used for radioimmunotherapy and
      radioscintigraphy of B-cell lymphoma in Iran.

PMID- 25074721
TI  - Prey capture kinematics in batoids using different prey types: investigating the
      role of the cephalic lobes.
AB  - Cephalic lobes are novel structures found in some myliobatid stingrays. While
      undulatory batoids utilize the pectoral fins for prey capture and locomotion,
      lobed species partition locomotion to the pectoral fins, utilizing the lobes
      exclusively for prey capture. We investigated the use of the anterior pectoral
      fins and cephalic lobes in prey capture in five batoid species. The purpose of
      this study was to investigate the: (1) prey capture kinematics and use of the
      cephalic lobes in lobed and lobeless batoids; (2) role of the cephalic lobes in
      modulating capture behavior based on prey type. It was hypothesized that lobed
      species would display unique capture behaviors resulting in faster and more
      successful capture of prey, and display greater modulation in capture behavior.
      Findings showed that lobed species used only the head region for capture, were
      faster at pouncing and tenting, but slower at mouth opening. The cephalic lobes
      were more movable than the anterior pectoral fins of lobeless species. Modulation
      occurred in all species. Elusive prey increased tent duration for the lobeless
      species, increased mouth opening duration in the lobed Aetobatus narinari, and
      were farther away from the mouth than non-elusive prey during biting for all
      species. All species had few prey escapes. Overall, species with cephalic lobes
      captured prey faster but did not display increased modulatory ability or feeding
      success. The cephalic lobes help localize prey capture to the head region,
      speeding up the prey capture event and maintaining an efficient capture rate
      despite having less flexible pectoral fins.

PMID- 25074722
TI  - Environment-dependent photon emission from solid state carbon dots and its
      mechanism.
AB  - Fluorescent carbon dots (CDs) have received great research interest in recent
      years, with applications in areas such as bio-imaging and chemical sensing.
      However, solid state photoluminescence of CDs and its related applications (e.g.
      optoelectronics) is a less explored territory. Here, we have systematically
      studied the photo emission of CDs in solid state. We found that their blue
      emission is highly dependent on whether the environment contains polar groups or
      not. Mechanism studies show that the blue emission of CDs may come from their C=O
      bonds conjugated with aromatic carbons, and the interaction between polar groups
      in environment and C=O bonds in CDs is responsible for the environment-dependent
      photo emission. Our conclusion here should assist the development of CDs' solid
      state applications.

PMID- 25074723
TI  - Impact of malpositioning on panoramic radiography in implant dentistry.
AB  - OBJECTIVES: The widely used panoramic radiography as a special kind of tomography
      underlies intrinsic procedural restrictions such as poor definition, inconsistent
      magnification, geometric distortion and spatial depositioning of objects situated
      outside the focal trough. This results in a non-anatomic display of the
      radiographed anatomic structures. Individual mandibular angle and width of the
      jaws, adjustment of the focal trough, jaw incongruence as well as patient
      positioning increase the inconsistency in display of the radiographed objects.
      This study precisely evaluated the quantitative impact of object malpositioning
      on the display in panoramic radiography. MATERIALS AND METHODS: A special dental
      implant model was highly accurate three dimensionally malpositioned and panoramic
      radiographs were taken. Automated image analysis was performed to exclude
      subjective assessment error. RESULTS: Precise and retraceable object deposition
      of up to 5 mm or 5 degrees  resulted in relevant deposition of objects and
      significant changes in object size and inter-object distances in the panoramic
      image. Unidirectional malpositioning lead to multiple errors in display.
      CONCLUSIONS: The extent of malpositioning-related display errors additionally to
      the known physicotechnical insufficiencies of the panoramic radiography
      demonstrates its limitations in precisely interpreting spatial relationships.
      CLINICAL RELEVANCE: Measurements within the panoramic radiography must not claim
      reliability. For a single object securely positioned in the focal trough and
      perpendicular to the central X-ray beam, measurements may be trustworthy on
      clinical scale. Once sterical relationships to other structures are evaluated,
      reliability must be questioned.

PMID- 25074724
TI  - Talking about end-of-life preferences in marriage: applying the theory of
      motivated information management.
AB  - The theory of motivated information management (TMIM) provides one framework to
      examine information-seeking behaviors, especially in conversations involving
      sensitive or difficult information such as preferences for end-of-life (EOL)
      care. The spouse plays a significant role in decision making surrounding EOL
      care. Consequently, individuals need information about spouses' EOL preferences
      in order to ensure carrying out those desires. Our findings support the value of
      TMIM as a framework to understand factors that influence couples' EOL care
      information-seeking behaviors. In support of the theory, we provide factors that
      influence the initiation or avoidance of EOL conversations between spouses. 

PMID- 25074725
TI  - Best practices for cardiovascular disease prevention in rheumatoid arthritis: a
      systematic review of guideline recommendations and quality indicators.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of mortality in
      rheumatoid arthritis (RA). This study systematically reviewed and appraised
      guidelines and quality indicators (QIs) pertaining to CVD risk management in
      patients with RA. METHODS: Four electronic medical databases (Medline, Embase,
      CINAHL, and Web of Science) and gray literature publications were searched using
      terms and keywords pertaining to guidelines, QIs, RA, and CVD (RA and general
      population literature searched). Abstracts were screened for inclusion and rated
      using the Appraisal of Guidelines for Research and Evaluation II instrument
      independently by 2 of 3 reviewers. RESULTS: In total, 16,064 abstracts were
      screened and 808 underwent full-text review. A total of 17 guidelines and 3 QI
      sets published between 2008 and 2013 were included. A number of consistent themes
      emerged, including the increased CV risk faced by RA patients and the need to
      address modifiable risk factors on a regular basis. The role of the
      multidisciplinary team in risk optimization was also highlighted. Ten guidelines
      provided recommendations for CVD prevention in patients with RA. Unfortunately,
      most recommendations lacked the specificity required to determine adherence to
      the recommendation. Only 4 RA-specific CVD QIs were identified (1 general
      comorbidity screening, formal CVD risk estimation, exercise, and minimizing
      steroid use). CONCLUSION: Regular screening for CVD risk factors is an important
      part of care in patients with RA. Unfortunately, existing RA-specific CVD QIs do
      not adequately address risk factor management, and existing guideline
      recommendations lack specificity for measurement and use in quality improvement
      initiatives.

PMID- 25074726
TI  - c-Met signalling is required for efficient postnatal thymic regeneration and
      repair.
AB  - We have reported that in vivo administration of the hybrid cytokine rIL-7/HGFbeta
      or rIL-7/HGFalpha, which contains interleukin-7 (IL-7) and the beta- or alpha
      chain of hepatocyte growth factor (HGF), significantly enhances thymopoiesis in
      mice after bone marrow transplantation. We have shown that the HGF receptor, c
      Met, is involved in the effect of the hybrid cytokines. To address the role of c
      Met signalling in thymocyte development and recovery, we generated conditional
      knockout (cKO) mice in which c-Met was specifically deleted in T cells by
      crossing c-Met(ft/ft) mice with CD4-Cre transgenic mice. We show here that
      although the number of total thymocytes and thymocyte subsets in young c-Met cKO
      mice is comparable to age-matched control (Ctrl) mice, the cKO mice were more
      susceptible to sub-lethal irradiation and dexamethasone treatment. This was
      demonstrated by low recovery in thymic cellularity in c-Met cKO mice after
      insult. Furthermore, the number of total thymocytes and thymocyte subsets was
      markedly reduced in 6- to 12-month-old cKO mice compared with age-matched Ctrl
      mice, and the thymic architecture of 12-month-old cKO mice was similar to that of
      20-month-old wild-type mice. In addition, c-Met deficiency reduced cell survival
      and the expression of Bcl-xL in double-positive thymocytes, and decreased cell
      proliferation and the expression of cyclin E and cyclin-dependent kinase 5 in
      single-positive thymocytes. Our data indicate that c-Met signalling plays an
      important role in thymic regeneration after thymic insult. In addition, T-cell
      specific inactivation of c-Met accelerates age-related thymic involution. 

PMID- 25074727
TI  - The detection of periapical pathoses in root filled teeth using single and
      parallax periapical radiographs versus cone beam computed tomography - a clinical
      study.
AB  - AIM: To clinically assess the diagnostic yield from single parallel periapical,
      two parallax radiographs and cone beam computed tomography (CBCT) by comparing
      the prevalence of periapical lesions associated with individual roots, and the
      total number of root canals in root-treated teeth in patients referred for root
      canal retreatment. METHODOLOGY: Single and parallax periapical radiographs, and
      CBCT scans, were taken of 100 teeth in 78 patients who had been referred for root
      canal retreatment. The presence of a periapical lesion associated with each
      specific root and the number of identifiable root canals were assessed using each
      imaging modality by a consensus panel of two examiners. The number of root canals
      was confirmed using the dental-operating microscope during treatment. In
      addition, the panel was asked to decide whether they felt they had adequate
      information to manage each case. RESULTS: A total of 209 paired roots were
      assessed for periapical lesions. Lesions were identified in 41%, 38% and 68% of
      paired roots when using single radiographs, two parallax radiographs and CBCT
      respectively. The number of root canals identified were 186, 218, 242 and 239
      when using parallel, parallax, CBCT and the dental-operating microscope,
      respectively. CONCLUSIONS: CBCT detected significantly more periapical lesions
      and root canals than both single and parallax periapical radiographs. There was
      no significant difference between CBCT and the clinical microscope in the
      identification of root canals. Whilst two parallax radiographs detect
      significantly more root canals than a single radiograph, they did not increase
      detection of periapical lesions when compared to a single periapical radiograph.

PMID- 25074728
TI  - Severity of mild cognitive impairment in early Parkinson's disease contributes to
      poorer quality of life.
AB  - BACKGROUND: Poor quality of life (QoL) is a feature of people with Parkinson's
      disease (PD) who develop dementia. The relationship between mild cognitive
      impairment in PD (PD-MCI) and QoL is less clear. To address this, we studied the
      impact of varying severities of cognitive impairment on QoL in a cohort of non
      demented patients with early PD. METHOD: Patients with newly diagnosed PD (n =
      219) and age and sex matched healthy controls (n = 99) completed a schedule of
      neuropsychological tests, in addition to scales assessing QoL (PDQ-39),
      depression, sleep, neuropsychiatric symptoms and a clinical examination. The
      Movement Disorder Society criteria were used to define and classify PD-MCI.
      RESULTS: Participants with PD-MCI were significantly older than those with normal
      cognition, had more severe motor symptoms, scored higher for depression and had
      poorer quality of life. Logistic regression showed that mild cognitive
      impairment, independent of other factors, was an indicator of poorer QoL. Using
      cognitive performance 2.0 standard deviations (SD) below normative data as a cut
      off to define PD-MCI, there was a significant difference in QoL scores between
      patients with PD-MCI and those classified as having normal cognition. Subjects
      with less severe mild cognitive impairment did not exhibit significant
      differences in QoL. CONCLUSIONS: PD-MCI is a significant, independent factor
      contributing to poorer QoL in patients with newly diagnosed PD. Those classified
      with greatest impairment (2.0 SD below normal values) have lower QoL. This has
      implications for clinical practice and future interventions targeting cognitive
      impairments.

PMID- 25074729
TI  - Dehydromethylation of alkali metal salts of the utility amide 2,2,6,6
      tetramethylpiperidide (TMP).
AB  - A general thermolysis reaction for the transformation of Group 1 TMP compounds
      (LiTMP, NaTMP, KTMP) to 1-aza-allylic TTHP derivatives is reported. TMEDA
      accelerates the reaction and produces the crystalline complexes [(TMEDA)LiTTHP]
      and [(TMEDA.NaTTHP)2]. Methane elimination during the transformational process
      was confirmed via TVA coupled to MS. 

PMID- 25074730
TI  - Low-heat treated autograft versus allograft for intercalary reconstruction of
      malignant bone tumors.
AB  - INTRODUCTION: Low-heat treated autograft may have an advantage over allograft in
      that they provide a size-matched and biologically compatible graft. MATERIALS AND
      METHODS: We compared the graft survival and complications between the low-heat
      treated autografts (n = 13) and allografts (17) for intercalary reconstruction of
      malignant bone tumors. Average age was 25 years with follow-up of 6.6 years (1.8
      12.5). For low-heat treatment, the resected bone was treated in saline at 65
      degrees C for 30 min. Nineteen grafts were fixed with plates and 13 with
      intramedullary nails. RESULTS: Until last follow-up, five low-heat treated
      autografts (38%) and one allograft (6%) had been removed, with allografts showing
      a trend toward better survival on Kaplan-Meier analysis (P = 0.293).
      Complications were more common in low-heat treated autograft group [10/13 (77%)
      vs. 8/17 (47%), P = 0.098)]. Low-heat-treated autograft resulted in significantly
      higher rate of nonunion [11/26 (42%) vs. 5/34 (15%), P = 0.017] and required
      higher number of operations to treat nonunion (P = 0.004). Rates of graft
      fracture [3/13 (23%) vs. 2/17 (12%), P = 0.713)] or infection [2/13 (15%) vs.
      1/17 (6%), P = 0.565)] were similar. CONCLUSION: Our data suggest that
      intercalary allograft has better survival and fewer complications than the low
      heat treated autograft.

PMID- 25074731
TI  - The origin of regional failure in oral cavity squamous cell carcinoma with
      pathologically negative neck metastases.
AB  - IMPORTANCE: Squamous cell carcinoma of the oral cavity (OSCC) is a common
      malignant tumor worldwide. OBJECTIVE: To determine if regional failure in
      patients with OSCC and pathologically negative neck nodes (pN-) is due to an
      incomplete sampling procedure during surgery. DESIGN, SETTING, AND PARTICIPANTS:
      We retrospectively reviewed the medical records of 2258 patients from 11 cancer
      centers worldwide who underwent neck dissection for OSCC (1990-2011) and who were
      pN-. Of those, 345 had clinical evidence of nodal metastases (cN+) on radiologic
      workup. The neck specimens were available for reanalysis in 193 patients.
      Survival rates were calculated using the Kaplan-Meier graphs and analyzed by
      multivariable analysis. MAIN OUTCOMES AND MEASURES: Five-year overall survival
      (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS:
      Resectioning and analysis of the neck dissection specimens in the cN+/pN-
      subgroup revealed false-negative results in 29 (15%) of 193 patients. The
      negative predictive value of the initial pathologic examination was 85%. The 5
      year OS and DSS in the cN-/pN- group were 77.6% and 87.2%, respectively. The 5
      year OS and DSS of the cN+/pN- group were 62.6% and 78.5%, respectively (P <
      .001). In multivariable analysis, cN+ classification was significantly associated
      with poor OS (hazard ratio [HR], 1.7; 95% CI, 1.1-3.8; P = .03) and poor DSS (HR,
      1.46; 95% CI, 1.1-4.1; P = .04). A cN+ classification was associated with lower
      DFS (66.3% vs 76.2%; P = .05) and lower regional recurrence-free survival (68.6%
      vs 78.8%; P = .02) but not with local (P = .20) or distant recurrence (P = .80).
      CONCLUSIONS AND RELEVANCE: Pathologic staging underestimates the incidence of
      nodal metastases in cN+ disease. After correction for pathologically missed nodal
      metastases, radiologic evidence of neck nodes is an independent predictor of
      outcome, suggesting that traditional sampling during surgery might miss
      metastases, and this fact might explain the origin of treatment failure in these
      patients.

PMID- 25074733
TI  - Comparison of the value of tissue-sealing devices for thoracoscopic pulmonary
      lobectomy in small children: a first report.
AB  - Accurate division and sealing of lung parenchyma particularly in cases of total
      or near total incomplete fissure are crucial for preventing air leakage following
      thoracoscopic pulmonary lobectomy (TPL). However, conventional endoscopic
      stapling devices cannot be used during TPL in small children because of limited
      space. Consequently, Ligasure (LS) and Enseal (ES) devices are being used
      instead. We are the first to compare LS and ES for efficacy and efficiency during
      TPL. Of 26 TPL (6 upper, 3 middle, and 17 lower) performed for congenital
      adenomatoid malformation (n = 16) and sequestration (n = 10), incomplete fissure
      was found in 14. TPL (LS = 11; ES = 15) was performed conventionally in the
      lateral decubitus position with single lung ventilation using four 5 mm trocars.
      All cases had a chest tube inserted intraoperatively that was left in situ.
      Patient demographics, location of pathology, incidence of incomplete fissure,
      mean age/weight at TPL, mean blood loss, and mean operative time were all
      similar. However, duration of chest tube insertion was significantly shorter in
      ES because there was less postoperative air leakage (1.3 vs. 3.9 days; p < 0.05).
      ES would appear to seal lung parenchyma more effectively during TPL based on the
      shorter duration of chest tube insertion. 

PMID- 25074732
TI  - Physiological analysis of the effects of rikkunshito on acid and non-acid
      gastroesophageal reflux using pH-multichannel intraluminal impedance monitoring.
AB  - PURPOSE: To clarify the effects of rikkunshito on acid reflux, non-acid reflux,
      and esophageal clearance in patients with gastroesophageal reflux disease (GERD).
      METHODS: We enrolled seven patients with vomiting and/or stridor (median 6 years;
      1 month-17 years), with a percent total time of esophageal pH <4.0 (reflux index)
      over 4.0%. Rikkunshito (TJ-43; Tsumura Co, Tokyo, Japan) was given in three
      divided doses before meals. We retrospectively investigated its efficacy using pH
      multichannel intraluminal impedance before and 7 (6-10) days after starting
      treatment. Statistical analyses were conducted using Wilcoxon signed-rank test.
      RESULTS: In the pH analyses alone, the median number of acid reflux episodes >5
      min (14 versus 10, p = 0.046) and median acid-clearance time (184 versus 134 s, p
      = 0.03) decreased significantly, although median decrease in reflux index did not
      reach significance (16.0 versus 17.9%, p = 0.06). In the combined impedance and
      pH analyses, the median number (36 versus 36, p = 0.03) and median duration (1.9
      versus 1.1%, p = 0.046) of acid reflux decreased significantly; non-acid reflux
      and bolus clearance time did not change. CONCLUSION: Rikkunshito effectively
      reduced acid reflux, but not esophageal clearance, in patients with GERD.

PMID- 25074734
TI  - Differential exercise effects on quality of life and health-related quality of
      life in older adults: a randomized controlled trial.
AB  - PURPOSE: Maintaining quality of life (QOL) and physical and mental health status
      are important outcomes throughout the aging process. Although cross-sectional
      studies suggest a relationship between global QOL and physical activity, it is
      unclear whether such a relationship exists as a function of exercise training.
      METHODS: We examined the effects of two exercise intervention arms on health
      related quality of life (HRQOL) and global QOL. Low-active, older adults (n =
      179) were randomly assigned to either a 12-month aerobic walking group or a
      strengthening and flexibility group. HRQOL and QOL were measured at baseline, 6,
      and 12 months. RESULTS: There was a significant group by time effect on QOL
      [F(2,176) = 3.11, p = 0.047, eta (2) = 0.03]. There was also a significant
      overall group by time effect for HRQOL [F(4,174) = 2.46, p = 0.047, eta (2) =
      0.05], which was explained by the significant group by time interaction for
      mental health status (p = 0.041, eta (2) = 0.02) favoring the walking condition.
      Further analyses using latent class analysis revealed three classes of
      individuals with differential patterns of change in QOL and HRQOL across time.
      These classes reflected no change, declines, and improvements in these constructs
      across time. CONCLUSIONS: Walking appears to enhance the mental aspect of HRQOL
      and global QOL when compared to a non-aerobic intervention. Additionally, the
      patterns of change in QOL and HRQOL were not linear over time. Our findings are
      in contrast to previous reports that these outcomes change a little or not at all
      in randomized trials.

PMID- 25074735
TI  - Intoxication at last sexual intercourse and unprotected sex among HIV-positive
      and HIV-negative individuals in Uganda: an event-level analysis.
AB  - This study examined, for the first time, the association between intoxication at
      last sexual intercourse and unprotected sex separately among HIV-positive and HIV
      negative individuals. Data were derived from a nationally-representative survey
      of Uganda in 2011. Multivariable logistic regression analyses of the intoxication
      unprotected sex association included adjustment for sociodemographic and
      behavioral covariates that were also examined as moderators of the association.
      Among HIV-positive individuals, intoxication was associated with unprotected sex,
      whereas among HIV-negative individuals, the intoxication-unprotected sex
      association was moderated by knowledge that condoms prevent HIV transmission. The
      odds of unprotected sex was 2.67 times greater among HIV-negative individuals who
      were unaware that condoms prevent HIV, an association not observed among those
      who possessed such knowledge. The results suggest that the intoxication
      unprotected sex link be incorporated within Ugandan National HIV Prevention
      Strategies among HIV-positive and HIV-negative individuals. HIV-negative
      individuals who are unaware that condoms prevent HIV should be targeted for
      interventions focusing on increasing HIV transmission knowledge especially on the
      role of condoms in preventing the disease. The latter interventions should also
      identify those sociocultural and political beliefs about condom use that may
      serve as barriers to consistent condom use. 

PMID- 25074736
TI  - HIV Prevalence and Risk Behaviors Among Female Sex Workers in Botswana: Results
      from the 2012 HIV/STI Bio-Behavioral Study.
AB  - To evaluate HIV/STI prevalence among female sex workers (FSWs) in Botswana, and
      assess HIV-related risk behaviors. Cross-sectional study using time-location
      sampling in three districts of Botswana. Adjusted HIV prevalence at district
      level ranged from 53.5 to 68.5 %. Syphilis prevalence ranged from 3.7 to 14.5 %;
      chlamydia prevalence ranged from 4.8 to 16.3 %; and gonorrhoea prevalence ranged
      from 8.3 to 11.7 %. FSWs had been practicing sex work for a mean of 4.7 years,
      and had a mean of 7.6 sex partners in the week before the survey. While 67.1 % of
      FSWs surveyed reported always using condoms with clients in the past month. 59.5
      % reported one or more of the following: being paid more not to use a condom,
      having a condom break, or being forced not to use a condom by clients. Predictors
      of HIV infection in the multivariate analysis included: age (over 30 years),
      perceiving oneself to be at high risk of HIV, selling sex for 2 or more years,
      and having a mean of 11 or more partners in the last week. High HIV prevalence,
      high rates of partner exchange, a sizable population, and Inconsistent condom use
      combine together help fuel the country's hyper epidemic. HIV prevention
      interventions need to take into account the important influence of clients and
      boyfriends on condom use behavior.

PMID- 25074737
TI  - Uptake of HIV testing in substance use disorder treatment programs that offer on
      site testing.
AB  - Increasing rates of HIV testing within substance use disorder (SUD) treatment
      clients is an important public health strategy for reducing HIV transmission
      rates. The present study examined uptake of HIV testing among 1,224 clients in
      five SUD treatment units that offered on-site testing in Florida, New York, and
      California. Nearly one-third (30 %) of the participants, who had not previously
      tested positive, reported not having been tested for HIV within the past 12
      months. Women, African Americans, and injection drug users had a higher
      likelihood of having been tested within the past 12 months. The SUD treatment
      program was the most frequently identified location of participants' last HIV
      test. Despite the availability of free, on-site testing, a substantial proportion
      of clients were not tested, suggesting that strategies to increase uptake of
      testing should include addressing barriers not limited to location and cost.

PMID- 25074738
TI  - Two novel mutations in the fibrinogen gamma nodule.
AB  - INTRODUCTION: Congenital dysfibrinogenemia and hypofibrinogenemia are rare
      diseases characterized by inherited abnormality in the fibrinogen molecule,
      resulting in functional defects (dysfibrinogenemia) or low fibrinogen plasma
      levels (hypofibrinogenemia). MATERIALS AND METHODS: We have described two
      abnormal fibrinogens - fibrinogen Hranice (gamma Phe204Val) and Praha IV (gamma
      Ser313Gly). The carrier of the Hranice mutation was a 40-year-old female with low
      fibrinogen levels. The carrier of the Praha IV mutation was a 42-year-old man
      with a history of idiopathic thrombosis, low functional fibrinogen levels, and a
      prolonged thrombin time. RESULTS: Fibrin polymerization kinetics measurement was
      normal in both cases (after the addition of either thrombin or reptilase), as
      well as was fibrinolysis. Scanning electron microscopy and confocal microscopy
      revealed significantly wider fibers in both cases, when compared with fibers
      prepared from healthy control samples. Although both cases are situated in the
      gamma-nodule, they manifested differently. While the gamma Ser313Gly mutation
      manifested as dysfibrinogenemia with a thrombotic background, the gamma Phe204Val
      mutation manifested as hypofibrinogenemia without clinical symptoms. The mutation
      sites of both fibrinogens are in highly conserved regions of the fibrinogen gamma
      chains. gamma Ser313 is situated in a class 16:18 beta hairpin and is involved in
      hydrogen bonding with gamma Asp320. gamma Phe204 is situated in an inverse gamma
      turn and may be involved in pi-pi interactions. CONCLUSIONS: Both mutations cause
      conformational changes in fibrinogen, which lead either to impaired fibrinogen
      assembly (fibrinogen Hranice) or abnormal fibrinogen function (fibrinogen Praha
      IV).

PMID- 25074739
TI  - Platelet hyporeactivity in active myeloma.

PMID- 25074740
TI  - Residual perfusion defects in patients with pulmonary embolism are related to
      impaired fibrinolytic capacity.
AB  - BACKGROUND: Few studies investigated the relationship between fibrinolysis
      abnormalities and residual pulmonary perfusion defects after acute pulmonary
      embolism (PE). OBJECTIVE: To assess the fibrinolytic profile in patients with
      prior PE in relation to the extent of scintigraphically detectable residual
      perfusion abnormalities. PATIENTS AND METHODS: We studied 71 consecutive patients
      with a prior episode of PE, who were examined after one year of the incident
      embolic event, and at least one month after anticoagulation withdrawal. They
      underwent lung scintigraphy to assess the recovery of pulmonary perfusion,
      echocardiography and chest radiography to look for signs of pulmonary
      hypertension. Clot formation and lysis were evaluated by two turbidimetric
      methods: Clot and Lysis Assay and Clot Lysis Time. We also measured the in vitro
      plasmin-mediated lysis of fibrin from purified fibrinogen, and the circulating
      levels of fibrinolytic inhibitors. The sample was split in two categories based
      on the extent of residual perfusion defects: <10% (n=53), >= 10% (n=18). RESULTS:
      Patients with perfusion defects >10% had significantly longer lysis time
      (p<0.05), and higher levels of plasminogen activator inhibitor-1 (p<0.01) than
      those with perfusion defects <10%. The time interval between symptoms onset and
      PE diagnosis (time-to-diagnosis) was significantly longer in patients with
      perfusion defects >10% than in the others (p=0.005). In multivariate logistic
      regression, both lysis time and time-to-diagnosis were independently associated
      with perfusion defects >10% (p<0.001). None of the sampled patients had
      echocardiographic or radiologic signs of pulmonary hypertension. CONCLUSION:
      Prolonged time-to-diagnosis and fibrinolysis imbalance are independent predictors
      of incomplete perfusion recovery after acute PE.

PMID- 25074741
TI  - The behavioural response of mice lacking NK1 receptors to guanfacine resembles
      its clinical profile in treatment of ADHD.
AB  - BACKGROUND AND PURPOSE: Mice with functional ablation of substance P-preferring
      neurokinin-1 receptors (NK1R-/- mice) display behavioural abnormalities
      resembling those in attention deficit hyperactivity disorder (ADHD). Here, we
      investigated whether the ADHD treatment, guanfacine, alleviated the hyperactivity
      and impulsivity/inattention displayed by NK1R-/- mice in the light/dark
      exploration box (LDEB) and 5-choice serial reaction-time task (5-CSRTT),
      respectively. Following reports of co-morbid anxiety in ADHD, we also
      investigated effects of guanfacine on anxiety-like behaviour displayed by NK1R-/-
      and wild-type (WT) mice in the elevated plus maze (EPM). EXPERIMENTAL APPROACH:
      Mice were treated with guanfacine (0.1, 0.3 or 1.0 mg.kg(-1), i.p.), vehicle or
      no injection and tested in the 5-CSRTT or the LDEB. Only the lowest dose of
      guanfacine was used in the EPM assays. KEY RESULTS: In the 5-CSRTT, a low dose of
      guanfacine (0.1 mg.kg(-1)) increased attention in NK1R-/- mice, but not in WT
      mice. This dose did not affect the total number of trials completed, latencies to
      respond or locomotor activity in the LDEB. Impulsivity was decreased by the high
      dose (1.0 mg.kg(-1)) of guanfacine, but this was evident in both genotypes and is
      likely to be secondary to a generalized blunting of behaviour. Although the NK1R
      /- mice displayed marked anxiety-like behaviour, guanfacine did not affect the
      behaviour of either genotype in the EPM. CONCLUSIONS AND IMPLICATIONS: This
      evidence that guanfacine improves attention at a dose that did not affect arousal
      or emotionality supports our proposal that NK1R-/- mice express an attention
      deficit resembling that of ADHD patients.

PMID- 25074743
TI  - Imaging reveals the focal area of spreading depolarizations and a variety of
      hemodynamic responses in a rat microembolic stroke model.
AB  - Spreading depolarizations (SDs) occur in stroke, but the spatial association
      between SDs and the corresponding hemodynamic changes is incompletely understood.
      We applied multimodal imaging to visualize the focal area of selected SDs, and
      hemodynamic responses with SDs propagating over the ischemic cortex. The
      intracarotid infusion of polyethylene microspheres (d=45 to 53 MUm) produced
      multifocal ischemia in anesthetized rats (n=7). Synchronous image sequences
      captured through a cranial window above the frontoparietal cortex revealed:
      Changes in membrane potential (voltage-sensitive (VS) dye method); cerebral blood
      flow (CBF; laser speckle contrast (LSC) imaging); and hemoglobin (Hb)
      deoxygenation (red intrinsic optical signal (IOS) at 620 to 640 nm). A total of
      31 SD events were identified. The foci of five SDs were seen in the cranial
      window, originating where CBF was the lowest (56.9+/-9%), but without evident
      signs of infarcts. The hyperemic CBF responses to propagating SDs were coupled
      with three types of Hb saturation kinetics. More accentuated Hb desaturation was
      related to a larger decrease in CBF shortly after ischemia induction. Microsphere
      induced embolization triggers SDs in the rat brain, relevant for small embolic
      infarcts in patients. The SD occurrence during the early phase of ischemia is not
      tightly associated with immediate infarct evolution. Various kinetics of Hb
      saturation may determine the metabolic consequences of individual SDs. 

PMID- 25074744
TI  - Pial arteries respond earlier than penetrating arterioles to neural activation in
      the somatosensory cortex in awake mice exposed to chronic hypoxia: an additional
      mechanism to proximal integration signaling?
AB  - The pial and penetrating arteries have a crucial role in regulating cerebral
      blood flow (CBF) to meet neural demand in the cortex. Here, we examined the
      longitudinal effects of chronic hypoxia on the arterial diameter responses to
      single whisker stimulation in the awake mouse cortex, where activity-induced
      responses of CBF were gradually attenuated. The vasodilation responses to whisker
      stimulation under prehypoxia normal conditions were 8.1% and 12% relative to
      their baselines in the pial arteries and penetrating arterioles, respectively.
      After 3 weeks of hypoxia, however, these responses were significantly reduced to
      5.5% and 4.1%, respectively. The CBF response, measured using laser-Doppler
      flowmetry (LDF), induced by the same whisker stimulation was also attenuated (14%
      to 2.6%). A close linear correlation was found for the responses between the
      penetrating arteriolar diameter and LDF, and their temporal dynamics. After 3
      weeks of chronic hypoxia, the initiation of vasodilation in the penetrating
      arterioles was significantly extended, but the pial artery responses remained
      unchanged. These results show that vasodilation of the penetrating arterioles
      followed the pial artery responses, which are not explainable in terms of
      proximal integration signaling. The findings therefore indicate an additional
      mechanism for triggering pial artery dilation in the neurovascular coupling. 

PMID- 25074745
TI  - Characterization of cerebral glutamine uptake from blood in the mouse brain:
      implications for metabolic modeling of 13C NMR data.
AB  - (13)C Nuclear Magnetic Resonance (NMR) studies of rodent and human brain using [1
      (13)C]/[1,6-(13)C2]glucose as labeled substrate have consistently found a lower
      enrichment (~25% to 30%) of glutamine-C4 compared with glutamate-C4 at isotopic
      steady state. The source of this isotope dilution has not been established
      experimentally but may potentially arise either from blood/brain exchange of
      glutamine or from metabolism of unlabeled substrates in astrocytes, where
      glutamine synthesis occurs. In this study, the contribution of the former was
      evaluated ex vivo using (1)H-[(13)C]-NMR spectroscopy together with intravenous
      infusion of [U-(13)C5]glutamine for 3, 15, 30, and 60 minutes in mice. (13)C
      labeling of brain glutamine was found to be saturated at plasma glutamine levels
      >1.0 mmol/L. Fitting a blood-astrocyte-neuron metabolic model to the (13)C
      enrichment time courses of glutamate and glutamine yielded the value of glutamine
      influx, VGln(in), 0.036+/-0.002 MUmol/g per minute for plasma glutamine of 1.8
      mmol/L. For physiologic plasma glutamine level (~0.6 mmol/L), VGln(in) would be
      ~0.010 MUmol/g per minute, which corresponds to ~6% of the glutamine synthesis
      rate and rises to ~11% for saturating blood glutamine concentrations. Thus,
      glutamine influx from blood contributes at most ~20% to the dilution of
      astroglial glutamine-C4 consistently seen in metabolic studies using [1
      (13)C]glucose. 

PMID- 25074746
TI  - Accurate determination of blood-brain barrier permeability using dynamic contrast
      enhanced T1-weighted MRI: a simulation and in vivo study on healthy subjects and
      multiple sclerosis patients.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly
      used to estimate permeability in situations with subtle blood-brain barrier (BBB)
      leakage. However, the method's ability to differentiate such low values from zero
      is unknown, and no consensus exists on optimal selection of total measurement
      duration, temporal resolution, and modeling approach under varying physiologic
      circumstances. To estimate accuracy and precision of the DCE-MRI method we
      generated simulated data using a two-compartment model and progressively down
      sampled and truncated the data to mimic low temporal resolution and short total
      measurement duration. Model fit was performed with the Patlak, the extended
      Tofts, and the Tikhonov two-compartment (Tik-2CM) models. Overall, 17 healthy
      controls were scanned to obtain in vivo data. Long total measurement duration (15
      minutes) and high temporal resolution (1.25 seconds) greatly improved accuracy
      and precision for all three models, enabling us to differentiate values of
      permeability as low as 0.1 ml/100 g/min from zero. The Patlak model yielded
      highest accuracy and precision for permeability values <0.3 ml/100 g/min, but for
      higher values the Tik-2CM performed best. Our results emphasize the importance of
      optimal parameter setup and model selection when characterizing low BBB
      permeability. 

PMID- 25074748
TI  - 7.0 T MRI detection of cerebral microinfarcts in patients with a symptomatic high
      grade carotid artery stenosis.
AB  - In the current study, the presence of cerebral cortical microinfarcts (CMIs) was
      evaluated in a series of 21 patients with a symptomatic high-grade >50% stenosis
      of the carotid artery. A T2-weighted fluid-attenuated inversion recovery sequence
      and a T1-weighted turbo field echo sequence of the brain were obtained at 7.0
      Tesla magnetic resonance imaging. Primary study endpoint was the number of CMIs
      and macroinfarcts. In total, 53 cerebral infarcts (35 macroinfarcts; 18 CMIs)
      were found ipsilateral to the symptomatic carotid artery, in 14 patients (67%).
      In four of these patients, both CMIs and macroinfarcts were visible. In the
      contralateral hemisphere, seven infarcts (five macroinfarcts and two CMIs) were
      found in five patients (24%). In the ipsilateral hemispheres, the number of CMIs
      and macroinfarcts were significantly correlated (P=0.02). Unpaired comparison of
      medians showed that the number of CMIs in the ipsilateral hemisphere was
      significantly higher than the number of CMIs in the contralateral hemisphere
      (P=0.04). No significant correlation was found between stenosis grade and the
      number of any infarct. The current study shows that in symptomatic patients with
      significant extracranial carotid artery stenosis, CMIs are part of the total
      cerebrovascular burden and these CMIs prevail with a similar pattern as observed
      macroinfarcts. 

PMID- 25074749
TI  - Antenatal breast milk expression by women with diabetes for improving infant
      outcomes.
AB  - BACKGROUND: Some women with diabetes in pregnancy are encouraged to express and
      store colostrum prior to birthing. Following birth, the breastfed infant may be
      given the stored colostrum to minimise the use of artificial formula or
      intravenous dextrose administration if correction of hypoglycaemia is required.
      However, findings from observational studies suggest that antenatal breast milk
      expression may stimulate labour earlier than expected and increase admissions to
      special care nurseries for correction of neonatal hypoglycaemia. OBJECTIVES: To
      evaluate the benefits and harms of the expression and storage of breast milk
      during late pregnancy by women with diabetes. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2014).
      SELECTION CRITERIA: All published and unpublished randomised controlled trials
      comparing antenatal breast milk expressing with not expressing, by pregnant women
      with diabetes (pre-existing or gestational) and a singleton pregnancy. DATA
      COLLECTION AND ANALYSIS: Two review authors independently evaluated reports
      identified by the search strategy. MAIN RESULTS: There were no published or
      unpublished randomised controlled trials comparing antenatal expressing with not
      expressing. One randomised trial is currently underway. AUTHORS' CONCLUSIONS:
      There is no high level systematic evidence to inform the safety and efficacy of
      the practice of expressing and storing breast milk during pregnancy.

PMID- 25074750
TI  - [Health assessment of materials and articles for food contact under the Food and
      Feed Code: 216: Communication].

PMID- 25074747
TI  - Neurogenesis and inflammation after ischemic stroke: what is known and where we
      go from here.
AB  - This review covers the pathogenesis of ischemic stroke and future directions
      regarding therapeutic options after injury. Ischemic stroke is a devastating
      disease process affecting millions of people worldwide every year. The mechanisms
      underlying the pathophysiology of stroke are not fully understood but there is
      increasing evidence demonstrating the contribution of inflammation to the drastic
      changes after cerebral ischemia. This inflammation not only immediately affects
      the infarcted tissue but also causes long-term damage in the ischemic penumbra.
      Furthermore, the interaction between inflammation and subsequent neurogenesis is
      not well understood but the close relationship between these two processes has
      garnered significant interest in the last decade or so. Current approved therapy
      for stroke involving pharmacological thrombolysis is limited in its efficacy and
      new treatment strategies need to be investigated. Research aimed at new therapies
      is largely about transplantation of neural stem cells and using endogenous
      progenitor cells to promote brain repair. By understanding the interaction
      between inflammation and neurogenesis, new potential therapies could be developed
      to further establish brain repair mechanisms. 

PMID- 25074751
TI  - Increased number of TH-immunoreactive cells in the ventral tegmental area after
      deep brain stimulation of the anterior nucleus of the thalamus.
AB  - Dopamine (DA) has been long implicated with the processes of memory. In long-term
      memory, the hippocampus and ventral tegmental area (VTA) use DA to enhance long
      term potentiation, while prefrontal DA D1 receptors are involved in working
      memory. Deep brain stimulation (DBS) of specific brain areas have been shown to
      affect memory impairments in animal models. Here, we tested the hypothesis that
      DBS could reverse memory impairments by increasing the number of dopaminergic
      cells in the VTA. Rats received DBS at the level of the mammillothalamic tract,
      the anterior nucleus of the thalamus, and entorhinal cortex before euthanasia.
      These regions are part of the so-called memory circuit. Brain sections were
      processed for c-Fos and tyrosine hydroxylase (TH) immunocytochemistry in the VTA
      and the substantia nigra pars compacta (SNc). c-Fos, TH and c-Fos/TH
      immunoreactive cells were analyzed by means of stereology and confocal
      microscopy. Our results showed that DBS of the anterior nucleus of the thalamus
      induced substantial higher numbers of TH-immunoreactive cells in the VTA, while
      there were no significant differences between the experimental groups in the
      number of TH immunoreactive cells in the SNc, c-Fos immunoreactive cells and c
      Fos/TH double-labeled cells in both the SNc and VTA. Our findings suggest a
      phenotypic switch, or neurotransmitter respecification, of DAergic cells
      specifically in the VTA which may be induced by DBS in the anterior nucleus of
      the thalamus.

PMID- 25074752
TI  - Identifying craniofacial features associated with prenatal exposure to androgens
      and testing their relationship with brain development.
AB  - We used magnetic resonance (MR) images obtained in same-sex and opposite-sex
      dizygotic twins (n = 119, 8 years of age) to study possible effects of prenatal
      androgens on craniofacial features. Using a principal component analysis of 19
      craniofacial landmarks placed on the MR images, we identified a principal
      component capturing craniofacial features that distinguished females with a
      presumed differential exposure to prenatal androgens by virtue of having a male
      (vs. a female) co-twin (Cohen's d = 0.76). Subsequently, we tested the
      possibility that this craniofacial "signature" of prenatal exposure to androgens
      predicts brain size, a known sexually dimorphic trait. In an independent sample
      of female adolescents (singletons; n = 462), we found that the facial signature
      predicts up to 8% of variance in brain size. These findings are consistent with
      the organizational effects of androgens on brain development and suggest that the
      facial signature derived in this study could complement other indirect measures
      of prenatal exposure to androgens.

PMID- 25074753
TI  - The potential of the F127-water soft system towards selective solubilisation of
      iridium(III) octahedral complexes.
AB  - In order to obtain new functional soft systems for use as templating agents for
      the construction of functional mesostructured materials, the dynamic ordered soft
      systems formed by a hydrophilic ionic iridium(III) complex (IrPa) embedded into
      two different concentration F127-water mixtures have been investigated. To this
      aim, combined spectral and time-resolved photophysical techniques and rheological
      methods have been employed. The position of the chromophore inside the micellar,
      cubic and hexagonal phases of the F127 polymeric neutral surfactant in water was
      effectively determined. The hydrophilic character of the iridium(III) complex
      chosen allowed preferential functionalization of the F127 corona in the micellar
      and cubic phases.

PMID- 25074754
TI  - Contact properties to CVD-graphene on GaAs substrates for optoelectronic
      applications.
AB  - The optimization of contacts between graphene and metals is important for many
      optoelectronic applications. In this work, we evaluate the contact resistance and
      sheet resistance of monolayer and few-layered graphene with different
      metallizations using the transfer length method (TLM). Graphene was obtained by
      the chemical vapor deposition technique (CVD-graphene) and transferred onto GaAs
      and Si/SiO2 substrates. To account for the quality of large-area contacts used in
      a number of practical applications, a millimeter-wide TLM pattern was used for
      transport measurements. Different metals--namely, Ag, Pt, Cr, Au, Ni, and Ti-
      have been tested. The minimal contact resistance Rc obtained in this work is 11.3
      kOmega MUm for monolayer CVD-graphene, and 6.3 kOmega MUm for a few-layered
      graphene. Annealing allows us to decrease the contact resistance Rc and achieve
      1.7 kOmegam MUm for few-layered graphene on GaAs substrate with Au contacts. The
      minimal sheet resistance Rsh of few-layered graphene transferred to GaAs and
      Si/SiO2 substrates are 0.28 kOmega/? and 0.27 kOmega/?. The Rsh value of
      monolayer graphene on the GaAs substrate is 8 times higher (2.3 kOmega/?), but it
      reduces for the monolayer graphene on Si/SiO2 (1.4 kOmega/?). For distances
      between the contacts below 5 MUm, a considerable reduction in the resistance per
      unit length was observed, which is explained by the changes in doping level
      caused by graphene suspension at small distances between contact pads.

PMID- 25074755
TI  - Chimeric antibodies with extended half-life in ferrets.
AB  - BACKGROUND: Ferrets have long been used as a disease model for the study of
      influenza vaccines, but a more recent use has been for the study of human
      monoclonal antibodies directed against influenza viruses. Published data suggest
      that human antibodies are cleared unusually quickly from the ferret and that
      immune responses may be partially responsible. This immunogenicity increases
      variability within groups and may present an obstacle to long-term studies.
      OBJECTIVE: Our aim was to identify an antibody design with reduced immunogenicity
      and longer circulating half-life in ferrets. METHODS: The constant region coding
      sequences for ferret immunoglobulin G were cloned, and chimeric human/ferret
      antibodies were expressed and purified. Some of the chimeric antibodies included
      substitutions that have been shown to extend the half-life of human IgG
      antibodies. These chimeric antibodies were tested for binding to recombinant
      ferret FcRn receptor and then evaluated in pharmacokinetic studies in ferrets.
      RESULTS: A one-residue substitution in the ferret Fc domain, S252Y, was
      identified that increased binding affinity to the ferret neonatal receptor by 24
      fold and extended half-life from 65 +/- 27 to 206 +/- 28 hours or ~9 days.
      Ferrets dosed twice with this surrogate antibody showed no indications of an
      immune response. CONCLUSION: Expressing the variable region of a candidate human
      therapeutic antibody with ferret constant regions containing the S252Y
      substitution can offer long half-life and limit immunogenicity.

PMID- 25074756
TI  - Treatment of facial erythema in patients with rosacea with topical brimonidine
      tartrate: correlation of patient satisfaction with standard clinical endpoints of
      improvement of facial erythema.
AB  - BACKGROUND: Once-daily brimonidine tartrate (BT) 0.5% gel was shown to provide
      significantly greater efficacy vs. vehicle for the treatment of facial erythema
      in patients with rosacea. OBJECTIVES: To demonstrate that patient satisfaction
      with overall appearance is correlated with reduction in facial erythema, as
      measured by clinician and patient assessments. METHODS: Data from two identical
      phase III, multicentre, randomized, controlled trials of moderate facial erythema
      of rosacea (study A: n = 260; study B: n = 293) with topical BT 0.5% compared to
      vehicle gel once-daily for 4 weeks were analysed. Correlations of Patient's
      Assessment of Appearance (PAA) with Clinician's Erythema Assessment (CEA) and
      Patient's Self-Assessment (PSA) of erythema were evaluated by calculation of
      gamma statistics. RESULTS: PAA correlated with CEA post-application on Days 1, 15
      and 29 for the intent-to-treat population and provided a median gamma value of
      0.57 (min = 0.28, max = 0.61). PAA and PSA was also highly correlated post
      application on Days 1, 15 and 29; with a median gamma value of 0.87 (min = 0.66,
      max = 0.89). Subjects who achieved a clinically meaningful improvement in both
      CEA and PSA scales were more likely to report satisfaction with the overall
      appearance of their skin (P < 0.001). CONCLUSIONS: Both one- and two-grade
      improvements in facial erythema assessed by subjects (PSA) and clinicians (CEA)
      correlate well with PAA, a patient-centered representation of meaningful change.

PMID- 25074757
TI  - Occupational injuries among children and adolescents in Cusco Province: a cross
      sectional study.
AB  - BACKGROUND: Although the number of child laborers in Latin America is generally
      high, data on occupational hazards and injuries is insufficient. The objective of
      this study was therefore to determine the lifetime prevalence of and risk factors
      for occupational injuries among working students (10-17 years old) in Cusco
      Province. METHODS: A cross-sectional study was conducted at five public night
      schools. 375 students (response 91.5%) completed an interview-based questionnaire
      on socio-demographics, work-related factors, and lifetime prevalence of
      occupational injuries. Multiple logistic regression analyses were performed to
      estimate risk factors for different types and causes of occupational injuries.
      RESULTS: Falls (11%), car accidents (9%) and physical violence (3%) were common
      causes of injuries in this population. Severe injuries (fractures, luxation or
      amputations) were reported by 3% of the population. A high daily income (>=20
      PEN, ~15 USD) was a statistically significant predictor for injuries caused by
      falls [OR 2.8; 95% CI 1.2-6.5] and physical violence at work [12.1; 1.3-115.9]
      whereas children born in Cusco and those working in the service sector were at
      higher risk of injuries caused by car accidents [3.7; 1.5-9.3 and 4.2; 1.2-15.3].
      CONCLUSIONS: Occupational accidents among child workers attending public night
      schools are common in Cusco with a lifetime prevalence of 3% for severe injuries.
      High income seems to convince child laborers to accept poor working conditions.

PMID- 25074760
TI  - Contemporary therapy of intracoronary thrombus: laser and bioresorbable scaffold.

PMID- 25074759
TI  - Infant neural sensitivity to dynamic eye gaze relates to quality of parent-infant
      interaction at 7-months in infants at risk for autism.
AB  - Links between brain function measures and quality of parent-child interactions
      within the early developmental period have been investigated in typical and
      atypical development. We examined such links in a group of 104 infants with and
      without a family history for autism in the first year of life. Our findings
      suggest robust associations between event related potential responses to eye gaze
      and observed parent-infant interaction measures. In both groups, infants with
      more positive affect exhibit stronger differentiation to gaze stimuli. This
      association was observed with the earlier P100 waveform component in the control
      group but with the later P400 component in infants at-risk. These exploratory
      findings are critical in paving the way for a better understanding of how infant
      laboratory measures may relate to overt behavior and how both can be combined in
      the context of predicting risk or clinical diagnosis in toddlerhood. 

PMID- 25074761
TI  - Histopathology of vascular response to drug-eluting stents: an insight from human
      autopsy into daily practice.
AB  - Drug-eluting stents (DES) were developed with the primary purpose of inhibiting
      neointimal overgrowth following percutaneous coronary intervention (PCI). While
      DES have significantly reduced the rates of restenosis compared with bare metal
      stent (BMS), they have not completely eliminated it. Moreover, late stent
      thrombosis (LST), attributed to delayed arterial healing or abnormal vessel
      responses to DES, have emerged as a major safety concern. Although newer DES or
      other novel devices are expected to show promising results, the problems in
      interventional technologies have not been completely resolved. In this review, we
      will consider the current status of DES in clinical practice and discuss the
      strengths and limitations of recent advances from the view of histopathology. 

PMID- 25074763
TI  - A(nother) test meant to fill the gap between in vivo and ex vivo hemostasis.

PMID- 25074762
TI  - Arabinogalactan glycosyltransferases target to a unique subcellular compartment
      that may function in unconventional secretion in plants.
AB  - We report that fluorescently tagged arabinogalactan glycosyltransferases target
      not only the Golgi apparatus but also uncharacterized smaller compartments when
      transiently expressed in Nicotiana benthamiana. Approximately 80% of AtGALT31A
      [Arabidopsis thaliana galactosyltransferase from family 31 (At1g32930)] was found
      in the small compartments, of which, 45 and 40% of AtGALT29A [Arabidopsis
      thaliana galactosyltransferase from family 29 (At1g08280)] and AtGlcAT14A
      [Arabidopsis thaliana glucuronosyltransferase from family 14 (At5g39990)]
      colocalized with AtGALT31A, respectively; in contrast, N-glycosylation enzymes
      rarely colocalized (3-18%), implicating a role of the small compartments in a
      part of arabinogalactan (O-glycan) biosynthesis rather than N-glycan processing.
      The dual localization of AtGALT31A was also observed for fluorescently tagged
      AtGALT31A stably expressed in an Arabidopsis atgalt31a mutant background.
      Further, site-directed mutagenesis of a phosphorylation site of AtGALT29A (Y144)
      increased the frequency of the protein being targeted to the AtGALT31A-localized
      small compartments, suggesting a role of Y144 in subcellular targeting. The
      AtGALT31A localized to the small compartments were colocalized with neither SYP61
      (syntaxin of plants 61), a marker for trans-Golgi network (TGN), nor FM4-64
      stained endosomes. However, 41% colocalized with EXO70E2 (Arabidopsis thaliana
      exocyst protein Exo70 homolog 2), a marker for exocyst-positive organelles, and
      least affected by Brefeldin A and Wortmannin. Taken together, AtGALT31A localized
      to small compartments that are distinct from the Golgi apparatus, the SYP61
      localized TGN, FM4-64-stained endosomes and Wortmannin-vacuolated prevacuolar
      compartments, but may be part of an unconventional protein secretory pathway
      represented by EXO70E2 in plants. 

PMID- 25074764
TI  - The impact of the extent of lymphadenectomy on oncologic outcomes in patients
      undergoing radical cystectomy for bladder cancer: a systematic review.
AB  - CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy
      (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder
      cancer (MIBC). OBJECTIVE: To systematically review the relevant literature
      assessing the impact of LND on oncologic and perioperative outcomes in patients
      undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process,
      Embase, the Cochrane Central Register of Controlled Trials, and the Latin
      American and Caribbean Center on Health Sciences Information (LILACS) were
      searched up to December 2013. Comparative studies reporting on no LND, limited
      LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE
      LND), and oncologic and perioperative outcomes were included. Risk-of-bias and
      confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies
      reporting on 19,793 patients were included. All but one study were retrospective.
      Planned meta-analyses were not possible because of study heterogeneity;
      therefore, data were synthesized narratively. There were high risks of bias and
      confounding across most studies as well as extreme heterogeneity in the
      definition of the anatomic boundaries of LND templates. All seven studies
      comparing LND with no LND favored LND in terms of better oncologic outcomes.
      Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a
      beneficial outcome for (super)extended LND in at least a subset of patients. No
      difference in outcome was reported in two studies comparing E-LND and S-LND. The
      comparative harms of different extents of LND remain unclear. CONCLUSIONS:
      Although the quality of the data was poor, the available evidence indicates that
      any kind of LND is advantageous over no LND. Similarly, E-LND appears to be
      superior to lesser degrees of dissection, while SE-LND offered no additional
      benefits. It is hoped that data from ongoing randomized clinical trials will
      clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests
      that removal of lymph nodes in bladder cancer surgery is beneficial and might
      result in better outcomes in terms of prolonging survival; however, the quality
      of the available studies is poor, and high-quality studies are needed.

PMID- 25074765
TI  - Statin treatment reduces the risk of hepatocellular carcinoma but not colon
      cancer-results from a nationwide case-control study in Sweden.
AB  - BACKGROUND: Several studies have indicated that statins may have anticarcinogenic
      effects. The aim of the present study was to investigate if statin treatment was
      associated with a reduced risk of hepatocellular carcinoma (HCC) or colon cancer.
      METHODS: A nationwide case-control study was carried out in which all cases of
      HCC and colon cancer in the Swedish population above 40 years of age between 1
      July 2006 and 31 December 2010 were identified in the Swedish Cancer Register.
      For every case, five controls were selected and matched on age and sex. Data on
      statin use was extracted from the Swedish Prescribed Drug Register. We estimated
      risks using conditional logistic regression and adjusted for educational level,
      concomitant medications and comorbidity. RESULTS: Identified were 3994 cases of
      HCC and matched with 19.970 controls, and 21.143 cases of colon cancer were
      identified and matched with 105.715 controls. In the adjusted analysis, the odds
      ratio (OR) for HCC among statin users was 0.88 (95% confidence interval (CI) 0.81
      0.96), and the OR for colon cancer was 1.04 (95%CI 1.00-1.08) compared with non
      users. CONCLUSION: Statin use was associated with a modest decreased risk of HCC
      but did not influence the risk of colon cancer. Future randomized placebo
      controlled trials in HCC high-risk patients are warranted to further investigate
      the possible prophylactic effect of statins in HCC.

PMID- 25074766
TI  - Hypothalamic alterations in Huntington's disease patients: comparison with
      genetic rodent models.
AB  - Unintended weight loss, sleep and circadian disturbances and autonomic
      dysfunction are prevalent features of Huntington's disease (HD), an autosomal
      dominantly inherited neurodegenerative disorder caused by an expanded CAG repeat
      sequence in the HTT gene. These features form a substantial contribution to
      disease burden in HD patients and appear to be accompanied by a number of
      neuroendocrine and metabolic changes, pointing towards hypothalamic pathology as
      a likely underlying mechanism. Neuronal inclusion bodies of mutant huntingtin,
      which are hallmarks of the disease, occur throughout the hypothalamus, and
      indicate local mutant huntingtin expression that could interfere with
      hypothalamic neuropeptide production. Also, several genetic rodent models of HD
      show features that could be related to hypothalamic pathology, such as weight
      loss and circadian rhythm disturbances. In these rodents, several hypothalamic
      neuropeptide populations are affected. In the present review, we summarise the
      changes in genetic rodent models of HD for individual hypothalamic nuclei,
      compare these observations to the hypothalamic changes that occur in HD patients,
      and make an inventory of the work that still needs to be done. Surprisingly,
      there is only limited overlap in the hypothalamic changes reported in HD patients
      and genetic rodent models. At present, the only similarity between the
      hypothalamic alterations in HD patients and genetic rodent models is a decrease
      in the number of orexin-expressing neurones in the lateral hypothalamus. Possible
      reasons for these discrepancies, as well as potential consequences for the
      development of novel therapeutic strategies, are discussed. 

PMID- 25074767
TI  - Nongenetic risk factors for neovascular age-related macular degeneration.
AB  - PURPOSE: To create a risk model for neovascular age-related macular degeneration
      (nAMD) based on nongenetic factors. METHODS: In this case-control study, 1459
      individuals were included, 445 patients showed nAMD and 1014 were healthy
      controls. Participants were randomly assigned into a training set (containing two
      thirds of individuals) and a validation set. Stepwise logistic regression
      analysis was performed for 25 environmental risk factors in the training set. The
      risk model with the remaining factors was then validated in the validation set
      using receiver operating characteristics (ROC) curve and Hosmer-Lemeshow-Test.
      Additionally, a genetic risk model including variants in the complement factor H
      gene (CFH, rs1061170) and the age-related maculopathy susceptibility 2 gene
      (ARMS2, rs10490924) was generated. RESULTS: The environmental risk model with the
      factors age, alcohol use, allergy, education, sunlight exposure, fish
      consumption, and physical exercise showed an AUC of 0.80 (95% confidence interval
      [CI] 0.76-0.84) in the training set. Validation of the model showed adequate
      calibration (Hosmer-Lemeshow P = 0.81). The AUC for the genetic model was 0.77
      (95% CI 0.730-0.808), for the combined environmental and genetic model 0.92 (95%
      CI 0.887-0.947). CONCLUSIONS: Seven nongenetic factors are able to provide
      equivalent discrimination between nAMD patients and controls to genetic risk
      models. Most of them are modifiable and give the opportunity for counseling
      patients.

PMID- 25074768
TI  - Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates
      monocyte chemotaxis.
AB  - PURPOSE: Uveal melanoma (UM) is the most common primary intraocular tumor in
      adults and the presence of infiltrating leucocytes is associated with a poor
      prognosis. Little is known how infiltrating leucocytes influence the tumor cells.
      The purpose of this study was to investigate the effect of activated T cells on
      the expression of chemotactic cytokines in UM cells. Furthermore, we examined the
      ability of stimulated UM cells to attract monocytes. METHODS: We used an in vitro
      coculture system in which UM cell lines and T cells were cultured together, but
      separated by a membrane. Uveal melanoma gene expression was quantified using a
      microarray. Protein expression in the supernatant was quantified with ELISA or
      cytometric bead array. For the monocyte migration assay, a transwell plate was
      used. RESULTS: Gene-expression analysis of UM cell lines showed that coculture
      with activated T cells resulted in an upregulation of chemokines such as CXCL8,
      CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1
      (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The
      upregulation of these molecules was confirmed at the protein level. This increase
      of chemokines coincided with an increased chemotactic capacity of the supernatant
      toward monocytes. CONCLUSIONS: Cytokines derived from activated T cells shifted
      the UM cell transcriptome toward a more inflammatory state, including
      upregulation of several chemokines, which led to an increased migration of
      monocytes. Therefore, UM cells might actively participate in generating a tumor
      promoting inflammatory microenvironment.

PMID- 25074769
TI  - Characteristics of fixational eye movements in people with macular disease.
AB  - PURPOSE: Fixation stability is known to be poor for people with macular disease
      and has been suggested as a contributing factor for the poor visual performance
      of these individuals. In this study, we examined the characteristics of the
      different components of fixational eye movements and determined the component
      that plays a major role in limiting fixation stability in people with macular
      disease. METHODS: Sixteen observers with macular disease and 14 older adults with
      normal vision (control observers) monocularly fixated a small cross presented
      using a Rodenstock scanning laser ophthalmoscope, for trials of 30 seconds. The
      retinal image and the position of the cross on the retina were recorded
      digitally. Eye movements were extracted from the recorded videos at a sampling
      rate of 540 Hz using a cross-correlation technique. A velocity criterion of 8
      degrees /s was used to differentiate between slow drifts and microsaccades.
      RESULTS: Observers with macular disease demonstrated higher fixation instability,
      larger amplitudes of slow drifts and microsaccades, and lower drift velocities,
      when compared with older adults with normal vision. The velocity and the rate of
      microsaccades were comparable between the two groups of observers. Multiple
      linear regression analysis showed that the amplitude of microsaccades, and to a
      smaller extent, the amplitude of slow drifts, play a major role in limiting
      fixation stability. CONCLUSIONS: Fixation stability in people with macular
      disease is primarily limited by the amplitude of microsaccades, implying that
      rehabilitative strategies targeted at reducing the amplitude of microsaccades
      should improve fixation stability, and may lead to improved visual functions.

PMID- 25074770
TI  - In vivo confocal microscopy of conjunctiva-associated lymphoid tissue in healthy
      humans.
AB  - PURPOSE: To investigate modifications with aging of the presence, distribution
      and morphologic features of conjunctiva-associated lymphoid tissue (CALT) in
      healthy human subjects using laser scanning in vivo confocal microscopy (IVCM).
      METHODS: A total of 108 (age range, 17-75 years) subjects were enrolled. In vivo
      confocal microscopy of the tarsal and bulbar conjunctiva, and impression cytology
      (IC) with CD3 (intra-epithelial T-lymphocytes) and CD20 (intra-epithelial B
      lymphocytes) antibody immunofluorescence staining were performed. The main
      outcomes were subepithelial lymphocyte density (LyD), follicular density (FD),
      and follicular area (FA). The secondary outcomes were follicular reflectivity
      (FR), and lymphocyte density (FLyD), and CD3 and CD20 positivity. RESULTS:
      Conjunctiva-associated lymphoid tissue was observed in all subjects (97% only
      superior and 3% in both superior and inferior tarsum). Lymphocyte density ranged
      from 7.8 to 165.8 cells/mm(2) (46.42 [18.37]; mean [SD]), FD from 0.5 to 19.4
      follicles/mm(2) (5.3 [3.6]), and FA from 1110 to 96,280 mm(2) (26,440 [26,280]).
      All three parameters showed a highly significant inverse cubic relationship with
      age (P < 0.001); that is, in the first and last parameters a steep decline up to
      35 years and above 65 years of age, with a plateau phase between these ages,
      whereas FA had a gradually decreasing rate of loss over the studied age range.
      CD3 and CD20 IC were consistent with these results. CONCLUSIONS: In vivo confocal
      microscopy was effective in revealing CALT and modifications these structures
      undergo with aging. Aging correlated with an involution of all parameters
      defining lymphoid structures. These modifications may account for the decrease of
      mucosal immune response and increase of ocular surface diseases in the elderly.

PMID- 25074771
TI  - Effects of a lutein supplement on the plasma lutein concentration and macular
      pigment in patients with central serous chorioretinopathy.
AB  - PURPOSE: To investigate the effects of lutein supplementation on plasma lutein
      concentrations and the macular pigment optical density (MPOD) in central serous
      chorioretinopathy (CSC). METHODS: In this double-masked placebo-controlled study,
      20 patients received lutein 20 mg/d and 19 received placebo. The plasma lutein
      concentration and MPOD using autofluorescence spectrometry (density unit, DU)
      were measured at baseline and 1 and 4 months. RESULTS: The mean plasma lutein
      concentrations and MPOD values in the lutein and control groups, respectively,
      were 91.5 and 78.2 ng/mL and 0.444 and 0.437 DU at baseline; 204.9 and 79.3 ng/mL
      and 0.460 and 0.442 DU at 1 month; and 228.0 and 78.4 ng/mL and 0.441 and 0.421
      DU at 4 months. The plasma concentration in the lutein group was significantly
      higher than in controls at 1 and 4 months (P < 0.0001 for both comparisons);
      however, the MPOD values did not differ significantly between groups at 1 (P =
      0.479) or 4 months (P = 0.883). In patients with a plasma lutein concentration
      below the mean level in 20 age-matched healthy subjects (mean 105.3 ng/mL; n = 13
      in lutein group, n = 15 in control group), the control MPOD values significantly
      (P = 0.0430) decreased at 4 months (mean baseline, 0.437 DU; 4 months, 0.404 DU).
      The MPOD in the lutein group remained at the baseline level (mean baseline, 0.426
      DU; 4 months, 0.438 DU) (P = 0.6542). CONCLUSIONS: The MPOD did not increase in
      patients with CSC with short-term lutein supplementation; however, among patients
      with low plasma lutein, supplemental lutein prevented a decline in MPOD that was
      observed in control subjects (www.umin.ac.jp/ctr number, UMIN000005849).

PMID- 25074773
TI  - Surface metrology and 3-dimensional confocal profiling of femtosecond laser and
      mechanically dissected ultrathin endothelial lamellae.
AB  - PURPOSE: To determine the feasibility of confocal profiling in measuring surface
      roughness and obtaining 3-dimensional reconstructions of mechanically dissected
      and femtosecond (fs)-laser photodisrupted endothelial lamellae. To determine the
      predictability of single-pass dissection of ultrathin endothelial lamellae using
      a novel motor-driven linear microkeratome. METHODS: Thirty (n = 30) human corneas
      were harvested using a motor-driven linear microkeratome (n = 20); a hand-driven
      rotatory microkeratome (n = 6); and a 60-kHz fs laser (n = 4). Surface roughness
      was measured using an optical profiler operated in confocal microscopy mode
      followed by environmental scanning-electron-microscopy. RESULTS: Mean surface
      roughness for the fs laser, motor-driven linear microkeratome, and hand-driven
      rotatory microkeratome measured 1.90 +/- 0.48 MUm, 1.06 +/- 0.42 MUm, and 0.93 +/
      0.25 MUm, respectively. Femtosecond photodisrupted lamellae were significantly
      rougher than mechanically dissected lamellae (P < 0.001). Mean (+/-SD) cutting
      depth with the motor-driven linear microkeratome measured: 552 +/- 11 MUm (550
      MUm head); 505 +/- 19 MUm (550-MUm head); 459 +/- 19 MUm (450-MUm head); and 392
      +/- 20 MUm (400-MUm head). CONCLUSIONS: Confocal microscopy allows quantitative
      surface roughness analysis and 3-dimensional reconstruction of human corneal
      lamellae. Femtosecond-laser photodisruption at 60 kHz results in rougher surfaces
      compared with mechanical dissection. The motor-driven linear microkeratome allows
      single-pass dissection of ultrathin endothelial lamellae with a standard
      deviation <=20 MUm.

PMID- 25074772
TI  - Choroidal and retinal thickening in severe preeclampsia.
AB  - PURPOSE: To compare choroidal thickness and retinal macular volume (RMV) among
      three groups of women: severe preeclampsia postpartum, normotensive postpartum,
      and normotensive nongravid. While visual disturbances often accompany severe
      preeclampsia, the underlying choroidal and retinal changes responsible for these
      symptoms have not been described. METHODS: This case-control study was based on
      15 severe preeclampsia cases and 15 ethnicity- and parity-matched normotensive
      controls recruited during the postpartum hospital stay. A reference group of 19
      age-matched, nongravid, normotensive women was also studied. Choroidal thickness
      and RMV were measured by using enhanced depth imaging spectral-domain optical
      coherence tomography. Two retinal specialists, one of whom was masked to the case
      control status, reviewed all images. RESULTS: Severe preeclampsia cases
      demonstrated greater mean choroidal thickness (425 +/- 90 MUm vs. 354 +/- 140
      MUm; P = 0.021) and RMV (9.0 +/- 0.4 mm(3) vs. 8.7 +/- 0.5 mm(3); P = 0.006) than
      controls. In contrast, control and reference groups were similar with respect to
      choroidal thickness (354 +/- 140 MUm vs. 363 +/- 82 MUm; P = 0.764) and RMV (8.7
      +/- 0.5 mm(3) vs. 8.8 +/- 0.4 mm(3); P = 0.870). Follow-up imaging of two severe
      preeclampsia cases within 3 months of delivery revealed decreasing choroidal
      thickness. CONCLUSIONS: Our results demonstrate subclinical retinal and choroidal
      thickening in the setting of severe preeclampsia. This is the likely source of
      its associated visual phenomena and may reflect rising levels of vascular
      endothelial growth factor. Retinal and choroidal markers could serve as novel
      predictive markers of severe preeclampsia.

PMID- 25074774
TI  - Repeatability and agreement of three Scheimpflug-based imaging systems for
      measuring anterior segment parameters in keratoconus.
AB  - PURPOSE: To assess the repeatability and agreement of three rotating Scheimpflug
      cameras, Pentacam, Galilei, and Sirius, in measuring the mean keratometry (Km),
      thinnest corneal thickness (TCT), anterior chamber depth (ACD), and mean
      posterior keratometry (pKm) in keratoconus patients in a prospective study.
      METHODS: Fifty-five eyes of 55 patients with keratoconus underwent three
      consecutive scans on each machine, performed by a single operator. Within-subject
      standard deviation (Sw), test-retest repeatability (TRT), and coefficient of
      variation (COV) for assessing repeatability and Bland-Altman plots for the
      agreement between the mean measurements of each machine were examined. RESULTS:
      The Sw of Km and pKm measurements with Pentacam (0.23 and 0.10 diopters [D],
      respectively) were significantly lower (better) than those of Galilei (0.60 and
      0.17) and Sirius (0.23 and 0.36). The Sw of TCT measurements with Sirius (8.88
      MUm) was significantly lower than that of Galilei (11.64 MUm). The COV ranged
      between 0.5 for the Km measurements of Pentacam and 2.8 for the TCT measurements
      of Galilei. Significant proportional bias in agreement was detected for the pKm
      measurements with all the three device pairs and for the ACD measurements between
      Pentacam and Galilei and between Galilei and Sirius. CONCLUSIONS: Though
      Pentacam, Galilei, and Sirius showed repeatable measurements for Km, TCT, ACD,
      and pKm, repeatabilities with Pentacam and Sirius were better than those with
      Galilei. There were significant differences in the measurements between the three
      devices; hence they cannot be used interchangeably for anterior segment
      measurements in keratoconus patients.

PMID- 25074775
TI  - Noninvasive evaluation of phase retardation in blebs after glaucoma surgery using
      anterior segment polarization-sensitive optical coherence tomography.
AB  - PURPOSE: Evaluation of bleb morphology using anterior segment optical coherence
      tomography (OCT) can offer important information regarding bleb function after
      glaucoma surgery. However, analysis of tissue properties, such as scar fibrosis
      of blebs, is difficult with conventional OCT. The birefringence of the blebs as
      susceptible measure of fibrosis scar was evaluated using polarization-sensitive
      OCT (PS-OCT) and its relation with bleb function was assessed. METHODS: One
      hundred and fifty-three blebs of 122 patients that had undergone trabeculectomy
      or an Ex-Press tube shunt were examined. Also, in 14 blebs of 12 patients,
      consecutive measurements were performed for 2 months after surgery. The
      birefringence of blebs was evaluated by measuring alteration of phase retardation
      using PS-OCT. Functionality of the bleb was classified according to IOP and
      medication. The bleb morphology in terms of size and characteristics was
      evaluated using three-dimensional (3D) cornea and anterior segment OCT. RESULTS:
      The alteration of phase retardation of blebs had the largest impact on bleb
      functionality than bleb morphology as shown by multiple regression analysis. In
      consecutive measurements, no blebs showed abnormal phase retardation until 1 week
      after surgery. Some blebs showed partial increase of phase retardation at 1 month
      after surgery. CONCLUSIONS: Intrableb fibrosis can be noninvasively evaluated
      with PS-OCT. Evaluation of birefringence by measuring phase retardation
      alterations using PS-OCT suggests new approaches for the postoperative management
      of glaucoma blebs regarding antifibrotic treatment for preventing IOP increases.

PMID- 25074777
TI  - Quantification of retinal nerve fiber and retinal artery trajectories using
      second-order polynomial equation and its association with axial length.
AB  - PURPOSE: To determine whether a second-degree polynomial equation can fit the
      retinal nerve fiber (RNF) and retinal artery (RA) trajectories in the posterior
      pole of eyes and whether the RNF and RA trajectories are correlated with the
      axial length of the eye. METHODS: This was a prospective observational cross
      sectional study of 109 right eyes of 109 healthy participants. All participants
      underwent axial length measurements, optical coherence tomography (OCT) to
      determine the peripapillary retinal nerve fiber layer (RNFL) thickness, and red
      free fundus photography. The supratemporal and infratemporal peaks of the RNFL
      thickness were determined in the OCT RNFL circle scan images. The trajectories of
      the RNF passing through the peaks of the RNFL thickness were plotted in the red
      free fundus photographs and were fitted to a second-degree polynomial equation
      (ax(2)/100 + bx + c) by ImageJ. The coefficient a represented the steepness of
      the trajectories. Intraclass correlation coefficient was used to measure the
      reliability between the raters. The relationships between the RNF or RA
      trajectories and the axial length were investigated using linear regression
      analyses. RESULTS: The mean axial length was 25.5 +/- 1.4 mm, and the mean RNF
      trajectory and the mean RA trajectory, a, were 0.472 +/- 0.123 and 0.442 +/-
      0.109, respectively. The intrarater and interrater correlation coefficients of
      the RNF trajectories were 0.954 and 0.881, respectively. The RNF and RA
      trajectories were significantly and positively correlated with the axial length
      (R = 0.28, 0.33, P < 0.01). CONCLUSIONS: A longer axial length is associated with
      narrower RNF and RA trajectories. (www.umin.ac.jp/ctr number, UMIN000006040.).

PMID- 25074776
TI  - TULP1 mutations causing early-onset retinal degeneration: preserved but
      insensitive macular cones.
AB  - PURPOSE: To investigate visual function and outer and inner retinal structure in
      the rare form of retinal degeneration (RD) caused by TULP1 (tubby-like protein 1)
      mutations. METHODS: Retinal degeneration patients with TULP1 mutations (n = 5;
      age range, 5-36 years) were studied by kinetic and chromatic static perimetry, en
      face autofluorescence imaging, and spectral-domain optical coherence tomography
      (OCT) scans. Outer and inner retinal laminar thickness were measured and mapped
      across the central retina. Comparisons were made with results from patients with
      RD associated with four ciliopathy genotypes (MAK, RPGR, BBS1, and USH2A).
      RESULTS: The TULP1-RD patients were severely affected already in the first decade
      of life and there was rapidly progressive visual loss. No evidence of rod
      function was present at any age. Small central islands showed melanized retinal
      pigment epithelium by autofluorescence imaging and well-preserved photoreceptor
      laminar thickness by OCT imaging. There was extracentral loss of laminar
      architecture and increased inner retinal thickening. Structure-function
      relationships in residual foveal cone islands were made in TULP1-RD patients and
      in other retinopathies considered ciliopathies. Patients with TULP1-RD, unlike
      the others, had greater dysfunction for the degree of foveal structural
      preservation. CONCLUSIONS: Retinal degeneration with TULP1 mutations leads to a
      small central island of residual foveal cones at early ages. These cones are less
      sensitive than expected from the residual structure. The human phenotype is
      consistent with experimental evidence in the Tulp1 knockout mouse model that
      visual dysfunction could be complicated by abnormal processes proximal to cone
      outer segments.

PMID- 25074778
TI  - Age-dependent changes in heparan sulfate in human Bruch's membrane: implications
      for age-related macular degeneration.
AB  - PURPOSE: Heparan sulfate (HS) has been implicated in age-related macular
      degeneration (AMD), since it is the major binding partner for complement factor H
      (CFH) in human Bruch's membrane (BrM), and CFH has a central role in inhibiting
      complement activation on extracellular matrices. The aim was to investigate
      potential aging changes in HS quantity and composition in human BrM. METHODS:
      Postmortem human ocular tissue was obtained from donors without known retinal
      disease. The HS was purified from BrM and neurosensory retina, and after
      digestion to disaccharides, fluorescently labeled and analyzed by reverse-phase
      HPLC. The HS and heparanase-1 were detected by immunohistochemistry in macular
      tissue sections from young and old donors, and binding of exogenously applied
      recombinant CCP6-8 region of CFH (402Y and 402H variants) was compared. RESULTS:
      Disaccharide analysis demonstrated that the mean quantity of HS in BrM was 50%
      lower (P = 0.006) in old versus young donors (average 82 vs. 32 years). In
      addition, there was a small, but significant decrease in HS sulfation in old BrM.
      Immunohistochemistry revealed approximately 50% (P = 0.02) less HS in macular BrM
      in old versus young donors, whereas heparanase-1 increased by 24% in old macular
      BrM (P = 0.56). In young donor tissue the AMD-associated 402H CCP6-8 bound
      relatively poorly to BrM, compared to the 402Y form. In BrM from old donors, this
      difference was significantly greater (P = 0.019). CONCLUSIONS: The quantity of HS
      decreases substantially with age in human BrM, resulting in fewer binding sites
      for CFH and especially affecting the ability of the 402H variant of CFH to bind
      BrM.

PMID- 25074742
TI  - Abdominal infections in the intensive care unit: characteristics, treatment and
      determinants of outcome.
AB  - BACKGROUND: Abdominal infections are frequent causes of sepsis and septic shock
      in the intensive care unit (ICU) and are associated with adverse outcomes. We
      analyzed the characteristics, treatments and outcome of ICU patients with
      abdominal infections using data extracted from a one-day point prevalence study,
      the Extended Prevalence of Infection in the ICU (EPIC) II. METHODS: EPIC II
      included 13,796 adult patients from 1,265 ICUs in 75 countries. Infection was
      defined using the International Sepsis Forum criteria. Microbiological analyses
      were performed locally. Participating ICUs provided patient follow-up until
      hospital discharge or for 60 days. RESULTS: Of the 7,087 infected patients, 1,392
      (19.6%) had an abdominal infection on the study day (60% male, mean age 62 +/- 16
      years, SAPS II score 39 +/- 16, SOFA score 7.6 +/- 4.6). Microbiological cultures
      were positive in 931 (67%) patients, most commonly Gram-negative bacteria
      (48.0%). Antibiotics were administered to 1366 (98.1%) patients. Patients who had
      been in the ICU for <= 2 days prior to the study day had more Escherichia coli,
      methicillin-sensitive Staphylococcus aureus and anaerobic isolates, and fewer
      enterococci than patients who had been in the ICU longer. ICU and hospital
      mortality rates were 29.4% and 36.3%, respectively. ICU mortality was higher in
      patients with abdominal infections than in those with other infections (29.4% vs.
      24.4%, p < 0.001). In multivariable analysis, hematological malignancy,
      mechanical ventilation, cirrhosis, need for renal replacement therapy and SAPS II
      score were independently associated with increased mortality. CONCLUSIONS: The
      characteristics, microbiology and antibiotic treatment of abdominal infections in
      critically ill patients are diverse. Mortality in patients with isolated
      abdominal infections was higher than in those who had other infections.

PMID- 25074779
TI  - Improvement of diagnostic performance regarding retinal nerve fiber layer defect
      using shifting of the normative database according to vessel position.
AB  - PURPOSE: To evaluate the clinical efficacy of early detection of retinal nerve
      fiber layer (RNFL) defect in a Korean population using shifting of the normative
      RNFL thickness database according to vessel position. METHODS: Retinal nerve
      fiber layer thickness data of 151 healthy eyes (normative group) and 120
      validation subjects (validation group; additional healthy controls plus early
      glaucoma) were prospectively obtained using spectral-domain optical coherence
      tomography (SD-OCT) measurement. Clinical profiles and position of major retinal
      artery peaks (superotemporal, STa; inferotemporal, ITa) were investigated with
      position of RNFL peaks. Three different criteria for the lower 1% limit were
      adopted for the validation. Criterion 1 used normative data from the
      manufacturer. Criterion 2 used data from healthy volunteers. Criterion 3 used
      four combinations of two subgroups from data for volunteers, which were divided
      by the median value of STa in the superior region and that of ITa in the inferior
      region. The kappa value was used to determine the diagnostic performance of each
      criterion (agreement with standard answer). RESULTS: Assessment of the validation
      group using criterion 3 showed greater accuracy than with criterion 1 or
      criterion 2 (kappa = 0.571, 0.774, and 0.979). Although SD-OCT specificity for
      RNFL defect detection was similar among the criteria (100%, 98.8%, and 98.9%),
      sensitivity was highest with criterion 3 (42.4%, 72.7%, and 100%) (all values;
      criteria 1, 2, and 3, respectively). CONCLUSIONS: Shifting of the lower 1%
      reference line, according to vessel position, could remarkably improve the
      diagnostic performance regarding RNFL defect detection with SD-OCT.

PMID- 25074780
TI  - The effect of fresh frozen plasma transfusion on international normalized ratio
      in emergency department patients.
AB  - BACKGROUND: There are few studies researching the effect of fresh frozen plasma
      (FFP) transfusion on international normalized ratio (INR) in patients with
      coagulation abnormality. OBJECTIVE: This study's aim was to determine the effect
      of FFP transfusion on INR as calculated pretransfusion. In addition, patients
      were grouped according to pretransfusion INR to determine the improvement in INR
      per unit of FFP. METHODS: Adult patients who had been admitted to our Emergency
      Department (ED) with coagulation abnormality and received an FFP transfusion, and
      had pre- and posttransfusion coagulation tests performed, were included in the
      study. Patients were categorized into five groups according to their
      pretransfusion INR levels. Improvement in INR per unit of FFP-transfused values
      (Delta INR 1 unit FFP) was determined for each group. RESULTS: Eighty-seven
      patients were entered into the study, and were administered a total of 199 units
      of FFP. Delta INR 1 unit FFP value was 0.03 +/- 0.13 for patients whose
      pretransfusion INR level was under 2; 0.77 +/- 0.47 for those between 2 and 5;
      2.14 +/- 0.63 for those between 5 and 9; 3.34 +/- 0.89 for those between 9 and
      12; and 4.63 +/- 1.99 for those over 12. A very strong positive correlation was
      found between pretransfusion INR and Delta INR 1 unit FFP (p < 0.001, r = 0.957).
      CONCLUSION: A significant improvement in INR was observed in patients with higher
      pretransfusion INR. While determining FFP dose for patients admitted to the ED
      due to coagulation defect, pretransfusion INR value should be taken into account.

PMID- 25074781
TI  - Factors associated with longer length of stay for mental health emergency
      department patients.
AB  - BACKGROUND: Mental health patients can experience long lengths of stay in the
      emergency department (ED). Reducing boarding times for mental health patients
      might improve care for all ED patients. OBJECTIVE: The objective of this study
      was to identify patient factors that are correlated with extremely long lengths
      of stay (EL-LOS) for mental health patients in the ED. METHODS: A retrospective,
      case-control study compared mental health patients experiencing lengths of stay
      longer than 24 h to those with lengths of stay <24 h. The study was conducted at
      an urban, academic ED and Level I trauma center. Sequential chi-squared tests
      were used to detect significant differences on the outcome measure. Logistic
      regression was used to determine factors that made significant contributions to
      predicting EL-LOS. The outcome measure was patients' length of stay in the ED.
      The factors analyzed were patient demographics, insurance status, day of arrival
      and departure, placement (admitted locally, admitted remotely, or discharged),
      chief complaint, and diagnostic category. RESULTS: Patient-level factors
      associated with EL-LOS were self-pay status, admission to inpatient care,
      transfer to a remote facility, and suicidal ideation. Admission to inpatient care
      and self-pay status made significant nonredundant contributions to predicting EL
      LOS. In addition, mental health patients arriving on a weekday were significantly
      more likely to be admitted to inpatient care than those arriving on weekends.
      CONCLUSIONS: Factors were identified that correlated with long lengths of stay in
      the ED for mental health patients. Increasing timely access to inpatient beds for
      mental health patients, in particular by improving access to insurance that
      covers inpatient psychiatric care and eliminating unique mental health
      requirements to obtain prior authorization for placement, would likely reduce
      these patients' lengths of stay.

PMID- 25074783
TI  - Do German hospital report cards have the potential to improve the quality of
      care?
AB  - BACKGROUND: Hospitals report cards have been put in place within the past few
      years to increase the amount of publicly reported quality information in Germany.
      OBJECTIVE: The aim of this study was to assess the potential of German hospital
      report cards to improve quality of care. METHODS: First, a systematic Internet
      search aimed at identifying available report cards was conducted. Second, cross
      sectional data (August/September 2013) were analyzed with respect to awareness,
      comprehension, and impact of report cards by using descriptive analysis and
      binary multivariate logistic regression models. RESULTS: Hospital report cards
      (N=62) have become broadly available. However, awareness remains low, about one
      third (35.6%) of all respondents (N=2027) were aware of German hospital report
      card. Regarding comprehensibility, in 60.7% of all experiments (N=6081),
      respondents selected the hospital with the lowest risk-adjusted mortality;
      significant differences could be determined between the report cards (p<.001)
      with scores ranging from 27.5% to 77.2%. Binary multivariate logistic regression
      analysis revealed different significant respondent-related predictors on each
      report card. Finally, an impact on hospital choice making was determined.
      CONCLUSIONS: To increase the potential of hospital report cards, health policy
      makers should promote the availability of report cards. In addition, the
      comprehensibility of German hospital report cards cannot be regarded as
      satisfying and should be enhanced in the future.

PMID- 25074782
TI  - Effect of incubation temperature and time on the precision of data generated by
      antibiotic disc diffusion assays.
AB  - The influence on the precision of disc diffusion data of the conditions under
      which the tests were performed was examined by analysing multilaboratory data
      sets generated after incubation at 35  degrees C for 18 h, at 28  degrees C for
      24 h and 22  degrees C for 24 h and 48 h. Analyses of these data sets
      demonstrated that precision was significantly and progressively decreased as the
      test temperature was reduced from 35 to 22  degrees C. Analysis of the data
      obtained at 22  degrees C also showed the precision was inversely related to the
      time of incubation. Temperature and time related decreases in precision were not
      related to differences in the mean zone sizes of the data sets obtained under
      these test conditions. Analysis of the zone data obtained at 28 and 22  degrees C
      as single laboratory sets demonstrated that reductions of incubation temperature
      resulted in significant increases in both intralaboratory and interlaboratory
      variation. Increases in incubation time at 22  degrees C were, however,
      associated with statistically significant increases in interlaboratory variation
      but not with any significant increase in intralaboratory variation. The
      significance of these observations for the establishment of the acceptable limits
      of precision of data sets that can be used for the setting of valid
      epidemiological cut-off values is discussed. 

PMID- 25074784
TI  - Essential oil of Pinus koraiensis inhibits cell proliferation and migration via
      inhibition of p21-activated kinase 1 pathway in HCT116 colorectal cancer cells.
AB  - BACKGROUND: The essential oil of Pinus koraiensis (EOPK) is biologically active
      compound obtained from the leaves of P. koraiensis. The goal of this study was to
      investigate the anti-cancer mechanism of EOPK in HCT116 colorectal cancer cells.
      METHODS: HCT116 cell proliferation was assessed by conducting crystal violet and
      BrdU assays. To assess the effects of EOPK on cell migration, we performed a
      wound-healing assay. Further, the contribution of PAK1 to EOPK-induced AKT and
      extracellular signal-regulated kinase (ERK) suppression was assessed by siRNA
      mediated PAK1 knockdown. Changes to the expression and phosphorylation of PAK1
      and its effectors were determined by western blotting, and changes to the actin
      cytoskeleton were determined by performing an immunofluorescence assay. RESULTS:
      EOPK significantly decreased HCT116 cell proliferation and migration, and induced
      G1 arrest without affecting normal cells. Additionally, EOPK suppressed the
      expression of PAK1, and decreased ERK and AKT phosphorylation in HCT116 cells.
      Finally, EOPK suppressed beta-catenin, cyclin D1, and CDK4/6 expression.
      CONCLUSIONS: Our studies indicate that EOPK significantly reduced proliferation
      and migration of colorectal cancer cells. Furthermore, EOPK suppressed PAK1
      expression in a dose-dependent manner, and this suppression of PAK1 led to
      inhibition of ERK, AKT, and beta-catenin activities. Our findings suggest that
      EOPK exerts its anticancer activity via the inhibition of PAK1 expression,
      suggesting it may be a potent chemotherapeutic agent for colorectal cancer.

PMID- 25074785
TI  - RhD and haematopoietic transplantation.

PMID- 25074786
TI  - The picture of Dorian Gray: news from the red blood cell storage lesion.

PMID- 25074787
TI  - Safety of intravenous iron formulations: facts and folklore.

PMID- 25074788
TI  - Storing red blood cells with vitamin C and N-acetylcysteine prevents oxidative
      stress-related lesions: a metabolomics overview.
AB  - BACKGROUND: Recent advances in red blood cell metabolomics have paved the way for
      further improvements of storage solutions. MATERIALS AND METHODS: In the present
      study, we exploited a validated high performance liquid chromatography-mass
      spectrometry analytical workflow to determine the effects of vitamin C and N
      acetylcysteine supplementation (anti-oxidants) on the metabolome of erythrocytes
      stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol medium under
      blood bank conditions. RESULTS: We observed decreased energy metabolism fluxes
      (glycolysis and pentose phosphate pathway). A tentative explanation of this
      phenomenon could be related to the observed depression of the uptake of glucose,
      since glucose and ascorbate are known to compete for the same transporter. Anti
      oxidant supplementation was effective in modulating the redox poise, through the
      promotion of glutathione homeostasis, which resulted in decreased haemolysis and
      less accumulation of malondialdehyde and oxidation by-products (including
      oxidized glutathione and prostaglandins). DISCUSSION: Anti-oxidants improved
      storage quality by coping with oxidative stress at the expense of glycolytic
      metabolism, although reservoirs of high energy phosphate compounds were preserved
      by reduced cyclic AMP-mediated release of ATP.

PMID- 25074789
TI  - Supplementation of anti-oxidants in leucofiltered erythrocyte concentrates:
      assessment of morphological changes through scanning electron microscopy.

PMID- 25074790
TI  - IgA autoimmune haemolytic anaemia in a pregnant woman.

PMID- 25074791
TI  - Real-time phase-contrast flow MRI of the ascending aorta and superior vena cava
      as a function of intrathoracic pressure (Valsalva manoeuvre).
AB  - OBJECTIVE: Real-time phase-contrast flow MRI at high spatiotemporal resolution
      was applied to simultaneously evaluate haemodynamic functions in the ascending
      aorta (AA) and superior vena cava (SVC) during elevated intrathoracic pressure
      (Valsalva manoeuvre). METHODS: Real-time phase-contrast flow MRI at 3 T was based
      on highly undersampled radial gradient-echo acquisitions and phase-sensitive
      image reconstructions by regularized non-linear inversion. Dynamic alterations of
      flow parameters were obtained for 19 subjects at 40-ms temporal resolution, 1.33
      mm in-plane resolution and 6-mm section thickness. Real-time measurements were
      performed during normal breathing (10 s), increased intrathoracic pressure (10 s)
      and recovery (20 s). RESULTS: Real-time measurements were technically successful
      in all volunteers. During the Valsalva manoeuvre (late strain) and relative to
      values during normal breathing, the mean peak flow velocity and flow volume
      decreased significantly in both vessels (p < 0.001) followed by a return to
      normal parameters within the first 10 s of recovery in the AA. By contrast, flow
      in the SVC presented with a brief (1-2 heartbeats) but strong overshoot of both
      the peak velocity and blood volume immediately after pressure release followed by
      rapid normalization. CONCLUSION: Real-time phase-contrast flow MRI may assess
      cardiac haemodynamics non-invasively, in multiple vessels, across the entire
      luminal area and at high temporal and spatial resolution. ADVANCES IN KNOWLEDGE:
      Future clinical applications of this technique promise new insights into
      haemodynamic alterations associated with pre-clinical congestive heart failure or
      diastolic dysfunction, especially in cases where echocardiography is technically
      compromised.

PMID- 25074792
TI  - Altitudinal distribution patterns of soil bacterial and archaeal communities
      along mt. Shegyla on the Tibetan Plateau.
AB  - Unraveling the distribution patterns of plants and animals along the elevational
      gradients has been attracting growing scientific interests of ecologists, whether
      the microbial communities exhibit similar elevational patterns, however, remains
      largely less documented. Here, we investigate the biogeographic distribution of
      soil archaeal and bacterial communities across three vertical climate zones
      (3,106-4,479 m.a.s.l.) in Mt. Shegyla on the Tibetan Plateau, by combining
      quantitative PCR and high-throughput barcoded pyrosequencing approaches. Our
      results found that the ratio of bacterial to archaeal 16S rRNA gene abundance was
      negatively related with elevation. Acidobacteria dominated in the bacterial
      communities, Marine benthic group A dominated in the archaeal communities, and
      the relative abundance of both taxa changed significantly with elevation. At the
      taxonomic levels of domain, phylum, and class, more bacterial taxa than archaeal
      exhibited declining trend in diversity along the increasing elevational gradient,
      as revealed by Shannon and Faith's phylogenetic diversity indices. Unweighted
      UniFrac distance clustering showed that the bacterial communities from the
      mountainous temperate zone clustered together, whereas those from the subalpine
      cool temperate zone clustered together. However, the partitioning effect of
      elevational zones on the archaeal community was much weaker compared to that on
      bacteria. Redundancy analysis revealed that soil geochemical factors explained
      58.3 % of the bacterial community variance and 75.4 % of the archaeal community
      variance. Taken together, we provide evidence that soil bacteria exhibited more
      apparent elevational zonation feature and decreased diversity pattern than
      archaea with increasing elevation, and distribution patterns of soil microbes are
      strongly regulated by soil properties along elevational gradient in this plateau
      montane ecosystem.

PMID- 25074793
TI  - Viable but not culturable forms of Legionella pneumophila generated after heat
      shock treatment are infectious for macrophage-like and alveolar epithelial cells
      after resuscitation on Acanthamoeba polyphaga.
AB  - Legionella pneumophila, the causative agent of legionellosis is transmitted to
      human through aerosols from environmental sources and invades lung's macrophages.
      It also can invade and replicate within various protozoan species in
      environmental reservoirs. Following exposures to various stresses, L. pneumophila
      enters a non-replicative viable but non-culturable (VBNC) state. Here, we
      evaluated whether VBNC forms of three L. pneumophila serogroup 1 strains
      (Philadelphia GFP 008, clinical 044 and environmental RNN) infect differentiated
      macrophage-like cell lines (U937 and HL-60), A549 alveolar cells and Acanthamoeba
      polyphaga. VBNC forms obtained following shocks at temperatures ranging from 50
      to 70  degrees C for 5 to 60 min were quantified using a flow cytometric assay
      (FCA). Their loss of culturability was checked on BCYE agar medium. VBNC forms
      were systematically detected upon a 70  degrees C heat shock for 30 min. When
      testing their potential to resuscitate upon amoebal infection, VBNC forms
      obtained after 30 min at 70  degrees C were re-cultivated except for the clinical
      strain. No resuscitation or cell lysis was evidenced when using U937, HL-60, or
      A549 cells despite the use of various contact times and culture media. None of
      the strains tested could infect A. polyphaga, macrophage-like or alveolar
      epithelial cells after a 60-min treatment at 70  degrees C. However, heat-treated
      VBNC forms were able to infect macrophage-like or alveolar epithelial cells
      following their resuscitation on A. polyphaga. These results suggest that heat
      generated VBNC forms of L. pneumophila (i) are not infectious for macrophage-like
      or alveolar epithelial cells in vitro although resuscitation is still possible
      using amoeba, and (ii) may become infectious for human cell lines following a
      previous interaction with A. polyphaga.

PMID- 25074795
TI  - PACAP stimulates functional recovery after spinal cord injury through axonal
      regeneration.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective
      peptide expressed in the central nervous system. Although many studies have shown
      a neuroprotective effect of PACAP, the mechanism of PACAP in the treatment of
      spinal cord injury (SCI) is yet to be elucidated. The purpose of this study was
      to examine the efficacy and underlying mechanism of PACAP in a mouse SCI model
      where PACAP was delivered via a biodegradable hydrogel. When PACAP or saline was
      delivered immediately after SCI, the functional motor recovery 14 days after SCI
      was significantly improved in the PACAP group compared with that in the saline
      group. Expression levels of messenger RNA (mRNA) for collapsin response mediator
      protein 2 (CRMP2), a factor related to axonal regeneration, were increased in the
      PACAP group 14 days after SCI compared with those in the saline group. A
      significantly increased number of CRMP2-positive cells were observed around the
      injury lesion in the PACAP group, while CRMP2 co-labeling with neuronal and
      oligodendrocyte markers was detected in intact spinal cord. Fourteen days after
      SCI, anterograde tracing revealed that a significantly increased number of
      neuronal fibers extended caudally from the lesion epicenter in the PACAP group.
      These results suggest that PACAP stimulates functional motor recovery after SCI
      through axonal regeneration mediated by CRMP2. 

PMID- 25074796
TI  - A modelling approach to evaluate the long-term effect of soil texture on spring
      wheat productivity under a rain-fed condition.
AB  - Soil surface texture is an important environmental factor that influences crop
      productivity because of its direct effect on soil water and complex interactions
      with other environmental factors. Using 30-year data, an agricultural system
      model (DSSAT-CERES-Wheat) was calibrated and validated. After validation, the
      modelled yield and water use (WU) of spring wheat (Triticum aestivum L.) from two
      soil textures (silt loam and clay) under rain-fed condition were analyzed.
      Regression analysis showed that wheat grown in silt loam soil is more sensitive
      to WU than wheat grown in clay soil, indicating that the wheat grown in clay soil
      has higher drought tolerance than that grown in silt loam. Yield variation can be
      explained by WU other than by precipitation use (PU). These results demonstrated
      that the DSSAT-CERES-Wheat model can be used to evaluate the WU of different soil
      textures and assess the feasibility of wheat production under various conditions.
      These outcomes can improve our understanding of the long-term effect of soil
      texture on spring wheat productivity in rain-fed condition. 

PMID- 25074797
TI  - Assessment of placental volume and vascularization at 11-14 weeks of gestation in
      a Taiwanese population using three-dimensional power Doppler ultrasound.
AB  - BACKGROUND: The placental volume and vascular indices are crucial in helping
      doctors to evaluate early fetal growth and development. Inadequate placental
      volume or vascularity might indicate poor fetal growth or gestational
      complications. This study aimed to evaluate the placental volume and vascular
      indices during the period of 11-14 weeks of gestation in a Taiwanese population.
      METHODS: From June 2006 to September 2009, three-dimensional power Doppler
      ultrasound was performed in 222 normal pregnancies from 11-14 weeks of gestation.
      Power Doppler ultrasound was applied to the placenta and the placental volume was
      obtained by a rotational technique (VOCAL). The three-dimensional power histogram
      was used to assess the placental vascular indices, including the mean gray value,
      the vascularization index, the flow index, and the vascularization flow index.
      The placental vascular indices were then plotted against gestational age (GA) and
      placental volume. RESULTS: Our results showed that the linear regression equation
      for placental volume using gestational week as the independent variable was
      placental volume = 18.852 * GA - 180.89 (r = 0.481, p < 0.05). All the placental
      vascular indices showed a constant distribution throughout the period 11-14 weeks
      of gestation. A tendency for a reduction in the placental mean gray value with
      gestational week was observed, but without statistical significance. CONCLUSION:
      All the placental vascular indices estimated by three-dimensional power Doppler
      ultrasonography showed a constant distribution throughout gestation.

PMID- 25074799
TI  - Modeling factors predictive of functional improvement following acute stroke.
AB  - BACKGROUND: Predicting functional improvement at an early stage after stroke is
      critical to setting treatment goals and strategies. The aim of this study was to
      identify factors that can predict motor function improvement at 3 months and 6
      months poststroke. METHODS: Forty-four patients with stroke were included in the
      study. We recorded age, interval between stroke onset and initiation of physical
      therapy, stroke type, history of diabetes or cardiovascular disease, functional
      status prior to stroke, cognition, motivation, walking ability, eating ability,
      hemineglect, sensory function, and brain lesion site as predictive factors. The
      Stroke Rehabilitation Assessment of Movement, Berg Balance Scale, Timed Up & Go
      Test, and the 6-Minute Walk Test were conducted upon intake and at 3 months and 6
      months poststroke. Patients were assigned to a progressive group or a
      nonprogressive group based on their improvement in four functional measures.
      Variables for which there were significant group differences were used for
      stepwise discriminant analysis as determining factors and for setting the
      prediction model. RESULTS: Patient age, history of diabetes, functional status
      prior to stroke, and motivation were predictive factors of functional progress at
      3 months poststroke. Motivation and functional status prior to stroke predicted
      functional progress at 6 months poststroke. By comparing the discriminant
      function values of the progressive and nonprogressive groups, functional
      improvement can be predicted. CONCLUSION: Functional status prior to stroke and
      motivation are predictive of functional outcome at 3 months and 6 months
      poststroke. We have provided a formula that can be used to predict a patient's
      progress and then set treatment goals and programs accordingly.

PMID- 25074798
TI  - Bisphosphonate-related osteonecrosis of the jaw complicated by Ludwig's angina.
AB  - Ludwig's angina is a life-threatening cellulitis that involves the submandibular
      and sublingual spaces. It often occurs after an infection of the roots of the
      teeth. However, modern dental care and use of antibiotics for oral infections
      have made Ludwig's angina rare. We present here a cancer patient exhibiting the
      sequential features of bisphosphonate related osteonecrosis of the jaw on bone
      scan complicating with Ludwig's angina. This report highlights the need for
      medical practitioners to be alert to these rare combinations in the compromised
      patient after bisphosphonate therapy. To the best of our knowledge, no case of
      Ludwig's angina secondary to osteonecrosis of the jaw has been reported. 

PMID- 25074800
TI  - Hydrogen-hydrogen interaction in planar biphenyl: a theoretical study based on
      the interacting quantum atoms and Hirshfeld atomic energy partitioning methods.
AB  - The nature of H-H interaction between ortho-hydrogen atoms in planar biphenyl is
      investigated by two different atomic energy partitioning methods, namely
      fractional occupation iterative Hirshfeld (FOHI) and interacting quantum atoms
      (IQA), and compared with the traditional virial-based approach of quantum theory
      of atoms in molecules (QTAIM). In agreement with Bader's hypothesis of H-H
      bonding, partitioning the atomic energy into intra-atomic and interatomic terms
      reveals that there is a net attractive interaction between the ortho-hydrogens in
      the planar biphenyl. This falsifies the classical view of steric repulsion
      between the hydrogens. In addition, in contrast to the traditional QTAIM energy
      analysis, both FOHI and IQA show that the total atomic energy of the ortho
      hydrogens remains almost constant when they participate in the H-H interaction.
      Although, the interatomic part of atomic energy of the hydrogens plays a
      stabilizing role during the formation of the H-H bond, it is almost compensated
      by the destabilizing effects of the intra-atomic parts and consequently, the
      total energy of the hydrogens remains constant. The trends in the changes of
      intra-atomic and interatomic energy terms of ortho-hydrogens during H-H bond
      formation are very similar to those observed for the H2 molecule.

PMID- 25074801
TI  - Dendrite-free nanostructured anode: entrapment of lithium in a 3D fibrous matrix
      for ultra-stable lithium-sulfur batteries.
AB  - Entrapment of free lithium in a 3D fibrous Li7 B6 framework allows LiB
      nanostructured anodes with stable interfaces between the electrolyte and the
      electrode, which retards the formation of lithium dendrites. A lithium-sulfur
      cell with a nanostructured anode is created with a high Coulombic efficiency and
      high capacity retention rate of 36.3% after 2000 cycles. 

PMID- 25074802
TI  - Influence of body laterality on recovery from subjective visual vertical tilt
      after vestibular neuritis.
AB  - The subjective visual vertical (SVV) is an indicator of vestibular otolithic
      function and mainly processed by the nondominant parietal cortex. We investigated
      the hypothesis that recovery from SVV tilt after vestibular neuritis can be
      influenced by the body's lateral preference. This prospective cohort follow-up
      study included 254 consecutive adult patients with vestibular neuritis. The
      recovery from SVV tilt was faster in patients with a left hand or eye dominance
      than in those with a right dominance. While in left-handers the side of the
      neuritis did not affect the speed of recovery, in right-handed subjects, the
      recovery from a right-sided neuritis was significantly slower than from a left
      sided affection. These observations suggest that subjects with a left
      sensorimotor dominance have developed more significant midline-crossing
      projections to the parietal cortex, allowing them to cope faster with a
      unilateral vestibular deficit.

PMID- 25074803
TI  - Degradation of S-RNase in compatible pollen tubes of Solanum chacoense inferred
      by immunogold labeling.
AB  - The flowering plant Solanum chacoense uses an S-RNase-based self-incompatibility
      system in order to reject pollen that shares the same genes at the S-locus (S
      haplotype) with the style (an incompatible reaction). Two different models have
      been advanced to explain how compatible pollen tubes are protected from the
      cytotoxic effects of the S-RNase, sequestration of the S-RNase in a vacuolar
      compartment or degradation of the S-RNase in the cytoplasm. Here, we examine the
      subcellular distribution of an S11-RNase 18 and 24 h post pollination (hpp) in
      compatible and incompatible crosses by immunogold labeling and transmission
      electron microscopy. We find that the S-RNase is present in the cytoplasm of both
      compatible and incompatible crosses by 18 hpp, but that almost all the
      cytoplasmic S-RNase is degraded by 24 hpp in compatible crosses. These results
      provide compelling evidence that S-RNases are degraded in compatible but not in
      incompatible pollen tubes.

PMID- 25074804
TI  - Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and
      controlling GEF exposure.
AB  - Sustained forward migration through a fibrillar extracellular matrix requires
      localization of protrusive signals. Contact with fibronectin at the tip of a cell
      protrusion activates Rac1, and for linear migration it is necessary to dampen
      Rac1 activity in off-axial positions and redistribute Rac1 from non-protrusive
      membrane to the leading edge. Here, we identify interactions between coronin-1C
      (Coro1C), RCC2 and Rac1 that focus active Rac1 to a single protrusion. Coro1C
      mediates release of inactive Rac1 from non-protrusive membrane and is necessary
      for Rac1 redistribution to a protrusive tip and fibronectin-dependent Rac1
      activation. The second component, RCC2, attenuates Rac1 activation outside the
      protrusive tip by binding to the Rac1 switch regions and competitively inhibiting
      GEF action, thus preventing off-axial protrusion. Depletion of Coro1C or RCC2 by
      RNA interference causes loss of cell polarity that results in shunting migration
      in 1D or 3D culture systems. Furthermore, morpholinos against Coro1C or RCC2, or
      mutation of any of the binding sites in the Rac1-RCC2-Coro1C complex delays the
      arrival of neural crest derivatives at the correct location in developing
      zebrafish, demonstrating the crucial role in migration guidance in vivo. 

PMID- 25074805
TI  - STAG2 promotes error correction in mitosis by regulating kinetochore-microtubule
      attachments.
AB  - Mutations in the STAG2 gene are present in ~20% of tumors from different tissues
      of origin. STAG2 encodes a subunit of the cohesin complex, and tumors with loss
      of-function mutations are usually aneuploid and display elevated frequencies of
      lagging chromosomes during anaphase. Lagging chromosomes are a hallmark of
      chromosomal instability (CIN) arising from persistent errors in kinetochore
      microtubule (kMT) attachment. To determine whether the loss of STAG2 increases
      the rate of formation of kMT attachment errors or decreases the rate of their
      correction, we examined mitosis in STAG2-deficient cells. STAG2 depletion does
      not impair bipolar spindle formation or delay mitotic progression. Instead, loss
      of STAG2 permits excessive centromere stretch along with hyperstabilization of
      kMT attachments. STAG2-deficient cells display mislocalization of Bub1 kinase,
      Bub3 and the chromosome passenger complex. Importantly, strategically
      destabilizing kMT attachments in tumor cells harboring STAG2 mutations by
      overexpression of the microtubule-destabilizing enzymes MCAK (also known as
      KIF2C) and Kif2B decreased the rate of lagging chromosomes and reduced the rate
      of chromosome missegregation. These data demonstrate that STAG2 promotes the
      correction of kMT attachment errors to ensure faithful chromosome segregation
      during mitosis. 

PMID- 25074807
TI  - In vivo analysis of formation and endocytosis of the Wnt/beta-catenin signaling
      complex in zebrafish embryos.
AB  - After activation by Wnt/beta-Catenin ligands, a multi-protein complex assembles
      at the plasma membrane as membrane-bound receptors and intracellular signal
      transducers are clustered into the so-called Lrp6-signalosome [Corrected].
      However, the mechanism of signalosome formation and dissolution is yet not clear.
      Our imaging studies of live zebrafish embryos show that the signalosome is a
      highly dynamic structure. It is continuously assembled by Dvl2-mediated
      recruitment of the transducer complex to the activated receptors and partially
      disassembled by endocytosis. We find that, after internalization, the ligand
      receptor complex and the transducer complex take separate routes. The Wnt-Fz-Lrp6
      complex follows a Rab-positive endocytic path. However, when still bound to the
      transducer complex, Dvl2 forms intracellular aggregates. We show that this
      endocytic process is not only essential for ligand-receptor internalization but
      also for signaling. The MU2-subunit of the endocytic Clathrin adaptor Ap2
      interacts with Dvl2 to maintain its stability during endocytosis. Blockage of
      Ap2MU2 function leads to Dvl2 degradation, inhibiton of signalosome formation at
      the plasma membrane and, consequently, reduction of signaling. We conclude that
      Ap2MU2-mediated endocytosis is important to maintain Wnt/beta-catenin signaling
      in vertebrates.

PMID- 25074808
TI  - Proteomic analysis of mammalian sperm cells identifies new components of the
      centrosome.
AB  - Centrioles are evolutionarily conserved microtubule-based structures at the core
      of the animal centrosome that are essential for nucleating the axoneme of cilia.
      We hypothesized that centriole proteins have been under-represented in proteomic
      studies of the centrosome, because of the larger amount of pericentriolar
      material making up the centrosome. In this study, we have overcome this problem
      by determining the centriolar proteome of mammalian sperm cells, which have a
      pair of centrioles but little pericentriolar material. Mass spectrometry of sperm
      centrioles identifies known components of centrioles and many previously
      uncharacterized candidate centriole proteins. Assessment of localization of a
      subset of these candidates in cultured cells identified CCDC113, CCDC96, C4orf47,
      CCDC38, C7orf31, CCDC146, CCDC81 and CCDC116 as centrosome-associated proteins.
      We examined the highly conserved protein CCDC113 further and found that it is a
      component of centriolar satellites, is in a complex with the satellite proteins
      HAP1 and PCM1, and functions in primary cilium formation. 

PMID- 25074809
TI  - Dynamics of the circadian clock protein PERIOD2 in living cells.
AB  - In mammals, circadian rhythms are generated by delayed negative feedback, in
      which period (PER1-PER3) and cryptochrome (CRY1, CRY2) proteins gradually
      accumulate in the nucleus to suppress the transcription of their own genes.
      Although the importance of nuclear import and export signals for the subcellular
      localization of clock proteins is well established, little is known about the
      dynamics of these processes as well as their importance for the generation of
      circadian rhythms. We show by pharmacological perturbations of oscillating cells
      that nuclear import and export are of crucial importance for the circadian
      period. Live-cell fluorescence microscopy revealed that nuclear import of the key
      circadian protein PER2 is fast and further accelerated by CRY1. Moreover, PER2
      nuclear import is crucially dependent on a specific nuclear-receptor-binding
      motif in PER2 that also mediates nuclear immobility. Nuclear export, however, is
      relatively slow, supporting a model of PER2 nuclear accumulation by rapid import,
      slow export and substantial nuclear degradation. 

PMID- 25074806
TI  - p120-catenin regulates REST and CoREST, and modulates mouse embryonic stem cell
      differentiation.
AB  - Although the canonical Wnt pathway and beta-catenin have been extensively
      studied, less is known about the role of p120-catenin (also known as delta1
      catenin) in the nuclear compartment. Here, we report that p120-catenin binds and
      negatively regulates REST and CoREST (also known as Rcor1), a repressive
      transcriptional complex that has diverse developmental and pathological roles.
      Using mouse embryonic stem cells (mESCs), mammalian cell lines, Xenopus embryos
      and in vitro systems, we find that p120-catenin directly binds the REST-CoREST
      complex, displacing it from established gene targets to permit their
      transcriptional activation. Importantly, p120-catenin levels further modulate the
      mRNA and protein levels of Oct4 (also known as POU5F1), Nanog and Sox2, and have
      an impact upon the differentiation of mESCs towards neural fates. In assessing
      potential upstream inputs to this new p120-catenin-REST-CoREST pathway, REST gene
      targets were found to respond to the level of E-cadherin, with evidence
      suggesting that p120-catenin transduces signals between E-cadherin and the
      nucleus. In summary, we provide the first evidence for a direct upstream
      modulator and/or pathway regulating REST-CoREST, and reveal a substantial role
      for p120-catenin in the modulation of stem cell differentiation. 

PMID- 25074810
TI  - Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress
      from mammalian cells.
AB  - Iron (Fe(2+), Fe(3+)) homeostasis is a tightly regulated process, involving
      precise control of iron influx and egress from cells. Although the mechanisms of
      its import into cells by iron carrier molecules are well characterized, iron
      export remains poorly understood. The current paradigm envisages unique functions
      associated with specialized macromolecules for its cellular import (transferrin
      receptors) or export (ferroportin, also known as SLC40A1). Previous studies have
      revealed that iron-depleted cells recruit glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), a multitasking, 'moonlighting' protein, to their surface
      for internalization of the iron carrier holotransferrin. Here, we report that
      under the converse condition of intracellular iron excess, cells switch the
      isoform of GAPDH on their surface to one that now recruits iron-free
      apotransferrin in close association with ferroportin to facilitate the efflux of
      iron. Increased expression of surface GAPDH correlated with increased
      apotransferrin binding and enhanced iron export from cells, a capability lost in
      GAPDH-knockdown cells. These findings were confirmed in vivo utilizing a rodent
      model of iron overload. Besides identifying for the first time an apotransferrin
      receptor, our work uncovers the two-way switching of multifunctional molecules to
      manage cellular micronutrient requirements. 

PMID- 25074811
TI  - The guanine-exchange factor Ric8a binds to the Ca2+ sensor NCS-1 to regulate
      synapse number and neurotransmitter release.
AB  - The conserved Ca(2+)-binding protein Frequenin (homolog of the mammalian NCS-1,
      neural calcium sensor) is involved in pathologies that result from abnormal
      synapse number and probability of neurotransmitter release per synapse. Both
      synaptic features are likely to be co-regulated but the intervening mechanisms
      remain poorly understood. We show here that Drosophila Ric8a (a homolog of
      mammalian synembryn, which is also known as Ric8a), a receptor-independent
      activator of G protein complexes, binds to Frq2 but not to the virtually
      identical homolog Frq1. Based on crystallographic data on Frq2 and site-directed
      mutagenesis on Frq1, the differential amino acids R94 and T138 account for this
      specificity. Human NCS-1 and Ric8a reproduce the binding and maintain the
      structural requirements at these key positions. Drosophila Ric8a and Galphas
      regulate synapse number and neurotransmitter release, and both are functionally
      linked to Frq2. Frq2 negatively regulates Ric8a to control synapse number.
      However, the regulation of neurotransmitter release by Ric8a is independent of
      Frq2 binding. Thus, the antagonistic regulation of these two synaptic properties
      shares a common pathway, Frq2-Ric8a-Galphas, which diverges downstream. These
      mechanisms expose the Frq2-Ric8a interacting surface as a potential
      pharmacological target for NCS-1-related diseases and provide key data towards
      the corresponding drug design. 

PMID- 25074814
TI  - Larynx preservation protocols: long-term functional outcomes in good responders
      to induction chemotherapy for pyriform sinus carcinoma.
AB  - BACKGROUND/AIMS: Larynx preservation for laryngopharyngeal carcinomas aims to
      avoid the mutilation of a total laryngectomy without compromising survival or
      functionality. The aim of the present study on pyriform sinus squamous cell
      carcinoma (SCC) is to evaluate the long-term functional outcomes of larynx
      preservation in good responders to induction chemotherapy (ICT). METHODS: The
      study was carried out in a tertiary referral cancer center in France. The
      subjects were good responders to ICT for pyriform sinus SCC, subsequently treated
      with adjuvant radiation therapy (RT) - with or without concomitant chemotherapy -
      between 1999 and 2008. Only patients without recurrence at 3 years were included.
      The evaluated pharyngolaryngeal functions were airway patency, oral communication
      and oral feeding, based on a self-administered questionnaire and the patients'
      medical records. RESULTS: Twenty-eight patients were retained. Two (7%) patients
      needed a tracheotomy during or after the treatment and 2 (7%) had total
      laryngectomy for a late local recurrence. At least 3 years after the end of
      treatment, all patients were exclusively fed by mouth. All the evaluated patients
      judged their voice performance as 'adequate for everyday oral communication'.
      CONCLUSIONS: In the long run, patients with pyriform sinus SCC who are candidates
      for larynx preservation and respond favorably to ICT present a satisfactory
      functional outcome when treated with adjuvant RT.

PMID- 25074812
TI  - p300-mediated acetylation of COMMD1 regulates its stability, and the
      ubiquitylation and nucleolar translocation of the RelA NF-kappaB subunit.
AB  - Nucleolar sequestration of the RelA subunit of nuclear factor (NF)-kappaB is an
      important mechanism for regulating NF-kappaB transcriptional activity.
      Ubiquitylation, facilitated by COMMD1 (also known as MURR1), acts as a crucial
      nucleolar-targeting signal for RelA, but how this ubiquitylation is regulated,
      and how it differs from cytokine-mediated ubiquitylation, which causes
      proteasomal degradation of RelA, is poorly understood. Here, we report a new role
      for p300 (also known as EP300) in controlling stimulus-specific ubiquitylation of
      RelA, through modulation of COMMD1. We show that p300 is required for stress
      mediated ubiquitylation and nucleolar translocation of RelA, but that this effect
      is indirect. We also demonstrate that COMMD1 is acetylated by p300 and that
      acetylation protects COMMD1 from XIAP-mediated proteosomal degradation.
      Furthermore, we demonstrate that COMMD1 acetylation is enhanced by aspirin
      mediated stress, and that this acetylation is absolutely required for the protein
      to bind RelA under these conditions. In contrast, tumour necrosis factor (TNF)
      has no effect on COMMD1 acetylation. Finally, we demonstrate these findings have
      relevance in a whole tissue setting. These data offer a new paradigm for the
      regulation of NF-kappaB transcriptional activity, and the multiple other pathways
      controlled by COMMD1. 

PMID- 25074813
TI  - Phagosome maturation during endosome interaction revealed by partial rhodopsin
      processing in retinal pigment epithelium.
AB  - Defects in phagocytosis and degradation of photoreceptor outer segments (POS) by
      the retinal pigment epithelium (RPE) are associated with aging and retinal
      disease. The daily burst of rod outer segment (ROS) phagocytosis by the RPE
      provides a unique opportunity to analyse phagosome processing in vivo. In mouse
      retinae, phagosomes containing stacked rhodopsin-rich discs were identified by
      immuno-electron microscopy. Early apical phagosomes stained with antibodies
      against both cytoplasmic and intradiscal domains of rhodopsin. During phagosome
      maturation, a remarkably synchronised loss of the cytoplasmic epitope coincided
      with movement to the cell body and preceded phagosome-lysosome fusion and disc
      degradation. Loss of the intradiscal rhodopsin epitope and disc digestion
      occurred upon fusion with cathepsin-D-positive lysosomes. The same sequential
      stages of phagosome maturation were identified in cultured RPE and macrophages
      challenged with isolated POS. Loss of the cytoplasmic rhodopsin epitope was
      insensitive to pH but sensitive to protease inhibition and coincided with the
      interaction of phagosomes with endosomes. Thus, during pre-lysosomal maturation
      of ROS-containing phagosomes, limited rhodopsin processing occurs upon
      interaction with endosomes. This potentially provides a sensitive readout of
      phagosome-endosome interactions that is applicable to multiple phagocytes. 

PMID- 25074815
TI  - Phytochemical analysis and antileukemic activity of polyphenolic constituents of
      Toona sinensis.
AB  - Toona sinensis is a traditional Chinese medicine belonging to the Meliaceae
      family. The aim of this study was to identify the potential compounds responsible
      for anticancer activity of T. sinensis. The EtOAc extracts of leaves and woods of
      T. sinensis inhibited cell proliferation and induced apoptosis in human leukemia
      HL-60 cells. Our phytochemical research of these extracts led to the isolation of
      various polyphenolic constituents. The chemical structures were determined by
      spectroscopic analyses. Among isolates, gallic acid and loropetalin D showed
      inhibition of cell proliferation and possible induction of apoptosis in these
      cells. Overall, our results revealed the importance of T. sinensis as a
      chemopreventive medicinal plant. In addition, an analysis of structure-activity
      relationship indicated that the number of galloyl groups affects their
      antileukemic potency. 

PMID- 25074816
TI  - Incidence of physical disability related to musculoskeletal disorders in the
      elderly: results from a primary care-based registry.
AB  - OBJECTIVE: To estimate the incidence of musculoskeletal-related acute physical
      disability in the elderly (APDE). METHODS: A primary care-based registry was
      established in Madrid's Health Area 7 from October 1, 2005 to September 31, 2006.
      We included all persons age >=65 years, who were non-institutionalized and
      covered by the health cards assigned to the participating general practitioners
      (GPs). A case of APDE was defined as a moderate mobility alteration in the
      disability level within the Rosser's Classification System, in the last 3 months,
      related to a musculoskeletal cause. Incidence rates (IRs) were estimated per
      10,000 person-years by direct standardization with a 95% confidence interval (95%
      CI). RESULTS: Eight primary care centers and 23 GPs participated in the registry,
      covering 8,546 elderly patients. In the inclusion year, the GPs identified 147
      new APDE cases in 106 patients. The annual estimated incidence of APDE was 331
      cases per 10,000 person-years (95% CI 280-389) and the IR of new patients with an
      APDE episode was 239 (95% CI 196-288); the IR was higher in women (344 cases; 95%
      CI 279.8-423.0) than in men (207 cases; 95% CI 127.0-338.2). CONCLUSION: The
      incidence estimate of acute physical disability related to musculoskeletal
      disorders in the elderly should help us to determine the magnitude of this health
      problem, as well as the first step to establishing a specific practice for the
      recovery of cases and for the prevention of loss of functioning, mobility, and
      independence.

PMID- 25074817
TI  - Deformation of HyFlex CM instruments and their shape recovery following heat
      sterilization.
AB  - AIM: To assess the deformation of HyFlex CM instruments (Coltene Whaledent) when
      used in two instrumentation sequences and to assess their shape recovery after
      heat sterilization. METHODOLOGY: Simulated root canals with four different shapes
      were prepared with HyFlex CM instruments using a single-length technique (n = 40)
      or a crown down technique (n = 40). Pre-preparation, post-preparation and post
      sterilization standardized images of each instrument were recorded. Assessment of
      instrument deformation and their subsequent shape recovery was carried out
      visually and by comparing the digitised images. Data analysis was carried out
      using chi-square tests. RESULTS: None of the 400 instruments fractured. Visual
      assessment of instruments post-preparation revealed that 30.5% had unwound and
      0.5% had reverse winding. Following sterilization 8.5% remained unwound and 0.5%
      remained with reverse winding. When assessing instrument shape using digital
      images, 35.25% were unwound post-preparation, which reduced to 11% post
      sterilization. Nine size 25, 0.08 instruments deformed, but none fully regained
      their original shape after sterilization; however, other sizes of deformed
      instruments did regain their shape (P < 0.001). CONCLUSION: Approximately one
      third of instruments became deformed as a result of use. However, two thirds of
      these fully recovered their shape following sterilization. The number of deformed
      instruments was underestimated when no magnification was used for assessment.
      Instrument size was related to incidence of deformation and shape recovery.

PMID- 25074818
TI  - Normotopic cortex is the major contributor to epilepsy in experimental double
      cortex.
AB  - OBJECTIVE: Subcortical band heterotopia (SBH) is a cortical malformation formed
      when neocortical neurons prematurely stop their migration in the white matter,
      forming a heterotopic band below the normotopic cortex, and is generally
      associated with intractable epilepsy. Although it is clear that the band
      heterotopia and the overlying cortex both contribute to creating an abnormal
      circuit prone to generate epileptic discharges, it is less understood which part
      of this circuitry is the most critical. Here, we sought to identify the origin of
      epileptiform activity in a targeted genetic model of SBH in rats. METHODS: Rats
      with SBH (Dcx-KD rats) were generated by knocking down the Dcx gene using shRNA
      vectors transfected into neocortical progenitors of rat embryos. Origin, spatial
      extent, and laminar profile of bicuculline-induced interictal-like activity on
      neocortical slices were analyzed by using extracellular recordings from 60
      channel microelectrode arrays. Susceptibility to pentylenetetrazole-induced
      seizures was assessed by electrocorticography in head-restrained nonanesthetized
      rats. RESULTS: We show that the band heterotopia does not constitute a primary
      origin for interictal-like epileptiform activity in vitro and is dispensable for
      generating induced seizures in vivo. Furthermore, we report that most interictal
      like discharges originating in the overlying cortex secondarily propagate to the
      band heterotopia. Importantly, we found that in vivo suppression of neuronal
      excitability in SBH does not alter the higher propensity of Dcx-KD rats to
      display seizures. INTERPRETATION: These results suggest a major role of the
      normotopic cortex over the band heterotopia in generating interictal epileptiform
      activity and seizures in brains with SBH.

PMID- 25074819
TI  - Mode of action of dopamine in inducing hyperglycemia in the fresh water edible
      crab, Oziothelphusa senex senex.
AB  - The objective of this study was to investigate the mode of action of dopamine in
      regulating hemolymph sugar level in the fresh water edible crab, Oziothelphusa
      senex senex. Injection of dopamine produced hyperglycemia in a dose-dependent
      manner in intact crabs but not in eyestalkless crabs. Administration of dopamine
      resulted in a significant decrease in total carbohydrates and glycogen levels
      with a significant increase in glycogen phosphorylase activity levels in
      hepatopancreas and muscle of intact crabs, indicating dopamine-induced
      glycogenolysis resulting in hyperglycemia. Bilateral eyestalk ablation resulted
      in significant increase in the total carbohydrates and glycogen levels with a
      significant decrease in the activity levels of phosphorylase in the
      hepatopancreas and muscle of the crabs. Eyestalk ablation resulted in significant
      decrease in hemolymph hyperglycemic hormone levels. The levels of hyperglycemic
      hormone in the hemolymph of dopamine injected crabs were significantly higher
      than in control crabs. However, no significant changes in the levels of hemolymph
      hyperglycemic hormone and sugar and tissue carbohydrate and phosphorylase
      activity were observed in dopamine injected eyestalk ablated crabs when compared
      with eyestalk ablated crabs. These results support an earlier hypothesis in
      crustaceans that dopamine acts as a neurotransmitter and induces hyperglycemia by
      triggering the release of hyperglycemic hormone in the crab, O. senex senex.

PMID- 25074820
TI  - Representation of autism in leading newspapers in china: a content analysis.
AB  - The public's lack of understanding and the public's misconceptions about autism
      in China contribute to the underdiagnosis and undertreatment of the disorder and
      the stigma associated with it. Mass media are the primary channel through which
      people learn about autism. This article examines how leading newspapers in China
      covered autism in the 10-year period of 2003 through 2012 through a framing
      analysis. It finds that while autism has received increased media attention, it
      is increasingly framed as a family problem-family members are cited or quoted
      more than any other sources and the responsibility of dealing with autism is
      ultimately assigned to families. Autistic people are largely silenced unless they
      are autistic savants with special talents. The use of the scientific discourse
      and the human-interest discourse both decrease over time in percentage, while the
      use of other discourses such as the public relations discourse becomes more
      dominant. 

PMID- 25074821
TI  - Carbon coated face-centered cubic Ru-C nanoalloys.
AB  - Carbon-encapsulated ruthenium-carbon (Ru-C) nanoalloys were synthesized by
      dynamic shocks. The Ru-C alloy shows a new fcc structure different from the
      original hcp structure of metal Ru. This fcc phase is assigned to a Ru32C4 solid
      solution with a lattice parameter of 3.868(2) A and a bulk modulus KT0 of 272(12)
      GPa. The small amount of carbon in the solid solution enhances the thermodynamic
      and chemical stabilities with respect to pure Ru, as well as induces changes in
      the electronic properties, which have direct applications in improving the
      material's catalytic activity and selectivity. 

PMID- 25074822
TI  - Effects of land-use intensity on arthropod species abundance distributions in
      grasslands.
AB  - As a rule, communities consist of few abundant and many rare species, which is
      reflected in the characteristic shape of species abundance distributions (SADs).
      The processes that shape these SADs have been a longstanding problem for
      ecological research. Although many studies found strong negative effects of
      increasing land-use intensity on diversity, few reports consider land-use effects
      on SADs. Arthropods (insects and spiders) were sampled on 142 grassland plots in
      three regions in Germany, which were managed with different modes (mowing,
      fertilization and/or grazing) and intensities of land use. We analysed the effect
      of land use on three parameters characterizing the shape of SADs: abundance decay
      rate (the steepness of the rank abundance curve, represented by the niche
      preemption model parameter), dominance (Berger-Parker dominance) and rarity
      (Fisher's alpha). Furthermore, we tested the core-satellite hypothesis by
      comparing the species' rank within the SAD to their distribution over the land
      use gradient. When data on Araneae, Cicadina, Coleoptera, Heteroptera and
      Orthoptera were combined, abundance decay rate increased with combined land-use
      intensity (including all modes). Among the single land-use modes, increasing
      fertilization and grazing intensity increased the decay rate of all taxa, while
      increasing mowing frequency significantly affected the decay rate only in
      interaction with fertilization. Results of single taxa differed in their details,
      but all significant interaction effects included fertilization intensity.
      Dominance generally increased with increasing fertilization and rarity decreased
      with increasing grazing or mowing intensity, despite small differences among taxa
      and regions. The majority of species found on <10% of the plots per region were
      generally rare (<10 individuals), which is in accordance with the core-satellite
      hypothesis. We found significant differences in the rarity and dominance of
      species between plots of low and high intensity for all three land-use modes and
      for the combined land-use intensity. We conclude that effects of land-use
      intensity on SADs lead to a stronger dominance of the most abundant species.
      Furthermore, species which have restricted distributions are more likely to also
      be rare species in the local SAD and therefore are at high risk of being lost
      under intensive land use. 

PMID- 25074823
TI  - Expansion of ability of denitrification within the filamentous colorless sulfur
      bacteria of the genus Thiothrix.
AB  - Filamentous sulfur bacteria of the genus Thiothrix are able to respire nitrate
      (NO3-->NO2-) under anaerobic growth. Here, Thiothrix caldifontis (G1(T), G3),
      Thiothrix unzii (A1(T), TN) and Thiothrix lacustris AS were shown to be capable
      of further reduction of nitrite and/or nitrous oxides (denitrification). In
      particular, in the genomes of these strains, excluding T. unzii TN, the nirS gene
      encoding periplasmic respiratory nitrite reductase was detected, and for T.
      lacustris AS the nirS expression was confirmed during anaerobic growth. The nirK
      gene, coding for an alternative nitrite reductase, and the nrfA gene, encoding
      nitrite reduction to ammonia, were not found in any investigated strains. All
      Thiothrix species capable of denitrification possess the cnorB gene encoding
      cytochrome c-dependent NO reductase but not the qnorB gene coding for quinol
      dependent NO reductase. Denitrifying capacity ('full' or 'truncated') can vary
      between strains belonging to the same species and correlates with physical
      chemical parameters of the environment such as nitrate, hydrogen sulfide and
      oxygen concentrations. Phylogenetic analysis revealed the absence of recent
      horizontal transfer events for narG and nirS; however, cnorB was subjected to
      gene transfer before the separation of modern species from a last common ancestor
      of the Thiothrix species.

PMID- 25074824
TI  - The effect of chitosan and whey proteins-chitosan films on the growth of
      Penicillium expansum in apples.
AB  - BACKGROUND: Penicillium expansum causes a major post-harvest disease of apples.
      The aim of this study was to investigate the inhibition effect of chitosan and
      whey proteins-chitosan films containing different amounts of quince and cranberry
      juice against P. expansum on the simulation medium and on apples. The mechanical
      properties of films were also evaluated. RESULTS: The presence of cranberry and
      quince juice in the composition of chitosan and whey proteins-chitosan films
      caused a significant (P <= 0.05) increase in elasticity and decrease in tensile
      strength of films. Chitosan and whey proteins-chitosan films with quince and
      cranberry juice demonstrated a significant (P <= 0.05) inhibition effect against
      P. expansum growth on the simulated medium and apples. The presence of cranberry
      juice in the composition of chitosan and whey proteins-chitosan films resulted in
      a longer lag phase and a lower P. expansum growth rate on the simulation medium
      in comparison with films made with the addition of quince juice. These
      differences were not evident when experiment was conducted with apples.
      CONCLUSION: Addition of quince and cranberry juice to the chitosan and whey
      proteins-chitosan films as natural antifungal agents has some potential for
      prolonging the shelf life of apples.

PMID- 25074826
TI  - Toxic effects of sodium fluoride on cell proliferation and apoptosis of Leydig
      cells from young mice.
AB  - The biological effects of fluoride on human health are often extensive, either
      beneficial or detrimental. Among the various effects of fluoride exposure in
      different organs, the reproductive tract is particularly susceptible to
      disruption by fluoride at a sufficient concentration. It has attracted much
      attention to the effect of sodium fluoride on male fertility, gestational female,
      and offspring. Herein, we applied a widespread natural compound sodium fluoride
      (NaF) and investigated the effects of acute NaF exposure on Leydig cells,
      including their proliferation, apoptosis, and signal pathway changes. Our results
      demonstrated that high dosage of NaF could inhibit cell proliferation by stress
      induced apoptosis, which was confirmed by cellular and molecular evidences. We
      found that fluoride exposure affected the expression levels of stress response
      factors, signal transduction components, and apoptosis-related proteins,
      including caspase-3/caspase-9, B-cell lymphoma 2 (Bcl-2), and Bax. This study
      suggests that the complex effects of fluoride on Leydig cells are closely related
      to its dosage. 

PMID- 25074825
TI  - Mechanistic insight into beta-carotene-mediated protection against ulcerative
      colitis-associated local and systemic damage in mice.
AB  - PURPOSE: Ulcerative colitis (UC), a chronic gastrointestinal disorder, is a
      debilitating disease affecting many people across the globe. Research suggests
      that the levels of several antioxidants, including beta-carotene (beta-CAR),
      decrease in the serum of patients with UC. The present study was aimed at
      elucidating the molecular mechanisms involved in beta-CAR-mediated protection
      against UC in mice. METHODS: UC was induced in mice using 3%w/v dextran sulfate
      sodium in drinking water for two cycles; one cycle comprised of 7 days of dextran
      sulfate sodium-treated water followed by 14 days of normal drinking water. beta
      CAR was administered at the doses of 5, 10 and 20 mg/kg bw/day, po throughout the
      experiment. The effect of beta-CAR in mice with UC was evaluated using
      biochemical parameters, histological evaluation, comet and micronucleus assays,
      immunohistochemistry and Western blot analysis. RESULTS: The results indicated
      that beta-CAR treatment ameliorated the severity of UC by modulating various
      molecular targets such as nuclear factor-kappa B, cyclooxygenase-2, interleukin
      17, signal transducer and activator of transcription 3, nuclear erythroid 2
      related factor 2, matrix metalloproteinase-9 and connective tissue growth factor.
      Further, beta-CAR treatment maintained the gut integrity by increasing the
      expression of a tight junction protein, occludin, which was decreased in the
      colon of mice with UC. Also beta-CAR treatment significantly reduced UC
      associated elevated plasma lipopolysaccharide level, systemic inflammation and
      genotoxicity. CONCLUSION: beta-CAR ameliorated UC-associated local and systemic
      damage in mice by acting on multiple targets.

PMID- 25074827
TI  - Brain oscillatory activity during sleep shows unknown dysfunctions in early
      encephalopathy.
AB  - Electroencephalographic recordings in cirrhotic patients without overt hepatic
      encephalopathy (HE) have mainly been performed during wakefulness. Our aim was to
      quantify their alterations in nocturnal sleep electroencephalogram (EEG). In 20
      patients and 20 healthy volunteers, we recorded a nocturnal digital
      polysomnography. Different sleep parameters were measured. Besides, we performed
      quantitative analysis of EEG (qEEG) as follows: spectral power in the different
      sleep stages was calculated in the frequency bands low delta, delta, theta,
      alpha, and sigma. Also, the mean dominant frequency and Sleep Indexes were
      obtained. In comparison with controls, the group of patients showed (1) different
      alterations in both the microstructure and the macrostructure of sleep; (2) an
      increase in, both, theta band power and the average mean dominant frequency
      during rapid eye movement (REM); (3) in all sleep stages, a decrease of sleep
      electroencephalogram spectral power in low delta band and an increase in delta
      band: and (4) in stages N3 and REM, significant increases in the minimum of mean
      dominant frequency and in the respective sleep indexes. Therefore, in cirrhotic
      patients without overt HE, and likely having minimal hepatic encephalopathy, we
      found different alterations in both the microstructure and the macrostructure of
      nocturnal sleep. Also, sleep qEEG showed a brain dysfunction in slow oscillatory
      mechanisms intrinsic of sleep stages, with an increase in the frequency of its
      maximal electroencephalogram synchronization, from low delta to delta band. These
      alterations may reflect the onset of encephalopathy; sleep qEEG may, thus, be an
      adequate tool for its brain functional evaluation and follow-up. 

PMID- 25074828
TI  - Sociodemographic and hispanic acculturation factors and isolated anotia/microtia.
AB  - BACKGROUND: It has been observed in several studies that infants with
      anotia/microtia are more common among Hispanics compared with other racial/ethnic
      groups. We examined the association between selected Hispanic ethnicity and
      acculturation factors and anotia/microtia in the National Birth Defects
      Prevention Study. METHODS: We examined data from mothers of 351 infants with
      isolated anotia/microtia and 8435 unaffected infants from the National Birth
      Defects Prevention Study with an expected delivery date from 1997 to 2007.
      Sociodemographic, maternal, and acculturation factors (e.g., age, maternal
      education, household income, body mass index, gestational diabetes, folic acid,
      smoking, alcohol intake, study center, parental birthplace, and years lived in
      the United States, maternal language) were assessed as overall risk factors and
      also as risk factors among subgroups of Hispanics (United States- and foreign
      born) versus non-Hispanic whites. RESULTS: Compared with non-Hispanic whites,
      both United States- and foreign-born Hispanic mothers demonstrated substantially
      higher odds of delivering infants with anotia/microtia across nearly all strata
      of sociodemographic and other maternal factors (adjusted odds ratios range: 2.1
      11.9). The odds of anotia/microtia was particularly elevated among Hispanic
      mothers who emigrated from Mexico after age five (adjusted odds ratios = 4.88;
      95% confidence interval = 2.93-8.11) or who conducted the interview in Spanish
      (adjusted odds ratios = 4.97; 95% confidence interval = 3.00-8.24). CONCLUSION:
      We observed that certain sociodemographic and acculturation factors are
      associated with higher risks of anotia/microtia among offspring of Hispanic
      mothers.

PMID- 25074829
TI  - Association between particulate matter and its chemical constituents of urban air
      pollution and daily mortality or morbidity in Beijing City.
AB  - Recent time series studies have indicated that daily mortality and morbidity are
      associated with particulate matters. However, about the relative effects and its
      seasonal patterns of fine particulate matter constituents is particularly limited
      in developing Asian countries. In this study, we examined the role of particulate
      matters and its key chemical components of fine particles on both mortality and
      morbidity in Beijing. We applied several overdispersed Poisson generalized
      nonlinear models, adjusting for time, day of week, holiday, temperature, and
      relative humidity, to investigate the association between risk of mortality or
      morbidity and particulate matters and its constituents in Beijing, China, for
      January 2005 through December 2009. Particles and several constituents were
      associated with multiple mortality or morbidity categories, especially on
      respiratory health. For a 3-day lag, the nonaccident mortality increased by 1.52,
      0.19, 1.03, 0.56, 0.42, and 0.32% for particulate matter (PM)2.5, PM10, K(+),
      SO4(2-), Ca(2+), and NO3(-) based on interquartile ranges of 36.00, 64.00, 0.41,
      8.75, 1.43, and 2.24 MUg/m(3), respectively. The estimates of short-term effects
      for PM2.5 and its components in the cold season were 1 ~ 6 times higher than that
      in the full year on these health outcomes. Most of components had stronger
      adverse effects on human health in the heavy PM2.5 mass concentrations,
      especially for K(+), NO3(-), and SO4(2-). This analysis added to the growing body
      of evidence linking PM2.5 with mortality or morbidity and indicated that excess
      risks may vary among specific PM2.5 components. Combustion-related products,
      traffic sources, vegetative burning, and crustal component and resuspended road
      dust may play a key role in the associations between air pollution and public
      health in Beijing.

PMID- 25074830
TI  - Co-exposure of arsenic and cadmium through drinking water and tobacco smoking:
      risk assessment on kidney dysfunction.
AB  - The combined exposure of arsenic (As) and cadmium (Cd) causes more pronounced
      renal toxicity. The study aimed to evaluate the level of As and Cd in biological
      samples (blood and urine) of adults males, age ranged (30-50 years) exposed
      referent (ER) and exposed kidney patients (EKP), consumed contaminated drinking
      water of lake and smoking local cigarettes manufactured by tobacco plants grown
      on agricultural soil, irrigated with contaminated lake water. For comparative
      purpose age matched nonexoposed referent (NR) and nonexposed kidney patient
      (NKP), consumed municipal treaded water and smoking branded cigarette were also
      selected. The As and Cd levels in drinking water, biological samples, tobacco of
      branded and nonbranded cigarettes were analyzed using electrothermal atomic
      absorption spectrometry. The As and Cd concentrations in lake water were higher
      than the permissible limit recommended by the World Health Organization for
      drinking water. The As and Cd levels in local cigarette tobacco were found to be
      3- to 4-folds higher than branded cigarettes. The biochemical parameters
      especially urinary N-acetyl-beta-glucosaminidase (NAG) of ER, EKP, ER, and EKP
      subjects were studied as a biomarkers of renal dysfunction. The NAG values were
      found to be higher in EKP as compared to NKP (p < 0.01). The linear regressions
      showed higher correlations between As and Cd concentrations in water versus blood
      and urine samples of EKP (r = 0.71-0.78 and 0.68-0.72), as compared to NKP (p <
      0.05). 

PMID- 25074831
TI  - Determination of pesticide residues in fish tissues by modified QuEChERS method
      and dual-d-SPE clean-up coupled to gas chromatography-mass spectrometry.
AB  - The aim of this research was to modify the Quick, Easy, Cheap, Effective, Rugged
      and Safe (QuEChERS) method for the determination of organochlorine and
      organophosphate pesticides in fatty animal matrices such as fish muscle tissues
      of carp and sturgeon collected from Carp Valley, Lesser Poland. Pesticides
      extraction effectiveness was evaluated at 0.030 mg kg(-1) spiking level and
      efficiency of the dispersive-solid-phase extraction (d-SPE) clean-up step was
      evaluated by comparison testing two different d-SPE clean-up stages, first the
      addition of the d-SPE sorbent combination (PSA + SAX + NH2), and secondly the
      addition of C18 after extracts enrichment with the d-SPE sorbent combination (PSA
      + SAX + NH2), introducing a novel concept of clean-up named dual-d-SPE clean-up.
      Analysis of pesticide residues was performed by Gas Chromatography Quadrupole
      Mass Spectrometry (GC/Q-MS) working in selected-ion monitoring (SIM) mode. Linear
      relation was observed from 0 to 200 ng mL(-1) and determination coefficient R(2)
      > 0.997 in all instances for all target analytes. Better recoveries and
      cleanliness of extracts in both samples, carp and sturgeon tissues, were obtained
      after C18 addition during the dual-d-SPE clean-up step. Recoveries were in the
      range 70-120%, with relative standard deviation lower than 10% at 0.030 mg kg(-1)
      spiking level for most pesticides. LODs ranged 0.001-0.003 mg kg(-1), while LOQs
      ranged 0.004-0.009 mg kg(-1). The proposed method was successfully applied
      analyzing pesticide residues in real carp and sturgeon muscle samples; detectable
      pesticide residues were observed, but in all of the cases contamination level was
      lower than the default maximum residue levels (MRLs) set by the European Union
      (EU), Regulation (EC) N 396/2005.

PMID- 25074832
TI  - Growth inhibition of bloom forming cyanobacterium Microcystis aeruginosa by green
      route fabricated copper oxide nanoparticles.
AB  - The cyanobacterium Microcystis aeruginosa can potentially proliferate in a wide
      range of freshwater bionetworks and create extensive secondary metabolites which
      are harmful to human and animal health. The M. aeruginosa release toxic
      microcystins that can create a wide range of health-related issues to aquatic
      animals and humans. It is essential to eliminate them from the ecosystem with
      convenient method. It has been reported that engineered metal nanoparticles are
      potentially toxic to pathogenic organisms. In the present study, we examined the
      growth inhibition effect of green synthesized copper oxide nanoparticles against
      M. aeruginosa. The green synthesized copper oxide nanoparticles exhibit an
      excitation of surface plasmon resonance (SPR) at 270 nm confirmed using UV
      visible spectrophotometer. The dynamic light scattering (DLS) analysis revealed
      that synthesized nanoparticles are colloidal in nature and having a particle size
      of 551 nm with high stability at -26.6 mV. The scanning electron microscopy (SEM)
      analysis shows that copper oxide nanoparticles are spherical, rod and irregular
      in shape, and consistently distributed throughout the solution. The elemental
      copper and oxide peak were confirmed using energy dispersive x-ray analysis
      (EDAX). Fourier-transform infrared (FT-IR) spectroscopy indicates the presence of
      functional groups which is mandatory for the reduction of copper ions. Besides,
      green synthesized copper oxide nanoparticles shows growth inhibition against M.
      aeruginosa. The inhibition efficiency was 31.8 % at lower concentration and 89.7
      % at higher concentration of copper oxide nanoparticles, respectively. The
      chlorophyll (a and b) and carotenoid content of M. aeruginosa declined in dose
      dependent manner with respect to induction of copper oxide nanoparticles.
      Furthermore, we analyzed the mechanism behind the cytotoxicity of M. aeruginosa
      induced by copper oxide nanoparticles through evaluating membrane integrity,
      reactive oxygen species (ROS), and mitochondrial membrane potential (Deltapsim)
      level. The results expose that there is a loss in membrane integrity with ROS
      formation that leads to alteration in the Deltapsim, which ends up with severe
      mitochondrial injury in copper oxide nanoparticles treated cells. Hence, green
      way synthesized copper oxide nanoparticles may be a useful selective biological
      agent for the control of M. aeruginosa.

PMID- 25074833
TI  - Improved osteoblast response to UV-irradiated PMMA/TiO2 nanocomposites with
      controllable wettability.
AB  - Osteoblast response was evaluated with polymethylmethacrylate (PMMA)/titanium
      dioxide (TiO2) nanocomposite thin films that exhibit the controllable wettability
      with ultraviolet (UV) treatment. In this study, three samples of PMMA/TiO2 were
      fabricated with three different compositional volume ratios (i.e., 25/75, 50/50,
      and 75/25) followed by UV treatment for 0, 4, and 8 h. All samples showed the
      increased hydrophilicity after UV irradiation. The films fabricated with the
      greater amount of TiO2 and treated with the longer UV irradiation time increased
      the hydrophilicity more. The partial elimination of PMMA on the surface after UV
      irradiation created a durable hydrophilic surface by (1) exposing higher amount
      of TiO2 on the surface, (2) increasing the hydroxyl groups on the TiO2 surface,
      and (3) producing a mesoporous structure that helps to hold the water molecules
      on the surface longer. The partial elimination of PMMA on the surface was
      confirmed by Fourier transform infrared spectroscopy. Surface profiler and atomic
      force microscopy demonstrated the increased surface roughness after UV
      irradiation. Both scanning electron microscopy and energy-dispersive X-ray
      spectroscopy demonstrated that particles containing calcium and phosphate
      elements appeared on the 8 h UV-treated surface of PMMA/TiO2 25/75 samples after
      4 days soaking in Dulbecco's Modified Eagle Medium. UV treatment showed the
      osteoblast adhesion improved on all the surfaces. While all UV-treated
      hydrophilic samples demonstrated the improvement of osteoblast cell adhesion, the
      PMMA/TiO2 25/75 sample after 8 h UV irradiation (n = 5, P value = 0.000)
      represented the best cellular response as compared to other samples. UV-treated
      PMMA/TiO2 nanocomposite thin films with controllable surface properties represent
      a high potential for the biomaterials used in both orthopedic and dental
      applications. 

PMID- 25074834
TI  - Biomimetic remineralization of demineralized enamel with nano-complexes of
      phosphorylated chitosan and amorphous calcium phosphate.
AB  - Remineralization of enamel plays a crucial role in the progression of carious
      process and the management of early caries lesion. Based on the influence of
      phosphorylated proteins in biomineralization, the objective of this study was to
      synthesize nano-complexes of phosphorylated chitosan and amorphous calcium
      phosphate (Pchi-ACP), and evaluate their ability to remineralize enamel
      subsurface lesions in vitro. Pchi was synthesized using a previously established
      chemical method. The biomimetic remineralizing solution containing nano-complexes
      of Pchi-ACP was prepared by adding CaCl2 and K2HPO4 into Pchi-ACP solution (0.5 %
      w/v) in sequence. The final concentrations of calcium and phosphate ions were 10
      and 6 mM, respectively. The nano-complexes of Pchi-ACP were characterized by
      Fourier-transform infrared (FTIR), X-ray diffraction (XRD), transmission electron
      microscopy (TEM), and selected area electron diffraction (SAED). During testing
      the enamel lesions were treated with Pchi-ACP and fluoridated remineralizing
      solutions, respectively. The remineralizing of enamel lesions was examined with
      field emission electron microscope (FE-SEM) and Micro-CT. ACP was stabilized by
      Pchi to form nano-complexes that were soluble in water. The size of Pchi-ACP nano
      complexes particles was determined to be less than 50 nm. XRD and SAED results
      confirmed their amorphous phases. FE-SEM and Micro-CT results showed that the
      remineralizing effect of Pchi-ACP on enamel lesions was similar to that of
      fluoride. However, the remineralizing rate of Pchi-ACP treatment was
      significantly higher than that of fluoride treatment (P < 0.05). This study
      highlighted the potential of nanoparticles functionalized with a natural analogue
      involved in biomineralization, to remineralize early enamel caries. 

PMID- 25074835
TI  - Proteomic analisys of protein extraction during hemofiltration with on-line
      endogenous reinfusion (HFR) using different polysulphone membranes.
AB  - In end-stage renal disease patients, extracorporeal dialytic therapy is not able
      to prevent the accumulation of toxins related to the uremic syndrome, a severe
      complication that increases morbidity and mortality rate. In this paper,
      hemoFiltration with on-line Reinfusion (HFR) architecture is used to evaluate the
      effect of a more permeable membrane on the extraction of medium-high molecular
      weight molecules. The aim of this study was to compare two polysulphone membranes
      for convective chamber: polyphenylene High Flux (pHF) and polyphenylene Super
      High-Flux (pSHF). Fourteen patients were subjected to HFR with pHF and pSHF
      membranes and ultra filtrate (UF) samples were collected to evaluate molecular
      weight cut-off (MWCO) and to identify extracted proteins. Furthermore, image
      analysis software was used in order to evaluate change in protein extraction
      during the dialysis. The quantification of four proteins by immunoassay
      demonstrates a higher permeability of pSHF membrane. Two-dimensional
      electrophoresis (2-DE) gels showed, for both membranes, the greater number of
      protein spots at 235 min. Some of the identified proteins, involved in
      nephropathic disease complications, were compared to assess differences in
      extraction during dialytic treatment by PDQuest analysis. UF proteomic analysis
      demonstrated a different behavior for the two membranes; pHF membrane was more
      permeable at the beginning of HFR treatment (15 min), while pSHF membrane at the
      end of treatment (235 min). Proteomic analysis is a suitable approach to
      investigate the behavior of different membranes during dialysis. Results
      indicated that pSHF membrane offers the higher permeability, and showed higher
      efficiency in removal of middle molecules related to uremic syndrome. 

PMID- 25074837
TI  - Multimodal microscopy using 'half and half' contact mode and ultrasonic force
      microscopy.
AB  - Advances in the design and fabrication of multifunctional nanostructured
      materials require characterization techniques capable of simultaneously mapping
      multiple material properties with nanoscale resolution. We show that this can be
      achieved by combining nanomechanical information from ultrasonic force microscopy
      (UFM) with simultaneously acquired friction force and conductivity measurements
      from contact mode scanning. This utilizes a 'half and half' approach, where the
      AFM is operated alternatively in UFM and contact mode, with the switching rate
      sufficiently fast that simultaneous contact mode and UFM information is acquired
      at each pixel of an image. We demonstrate the potential of such a multimodal
      approach through its application to composite systems consisting of graphene
      islands on a copper surface, single-walled carbon nanotubes (SWNTs) on a silicon
      oxide substrate, and a graphene epoxy composite. The half and half approach
      enables the friction force to be measured without topographical cross-talk.
      Application to the SWNT sample reveals a further advantage; due to the
      superlubricity of UFM it enables standard contact mode imaging techniques to be
      applied to delicate samples. 

PMID- 25074836
TI  - Thermal behaviour and tolerance to ionic liquid [emim]OAc in GH10 xylanase from
      Thermoascus aurantiacus SL16W.
AB  - GH10 xylanase from Thermoascus aurantiacus strain SL16W (TasXyn10A) showed high
      stability and activity up to 70-75  degrees C. The enzyme's half-lives were 101
      h, 65 h, 63 min and 6 min at 60, 70, 75 and 80  degrees C, respectively. The
      melting point (T m), as measured by DSC, was 78.5  degrees C, which is in line
      with a strong activity decrease at 75-80  degrees C. The biomass-dissolving ionic
      liquid 1-ethyl-3-methylimidazolium acetate ([emim]OAc) in 30 % concentration had
      a small effect on the stability of TasXyn10A; T m decreased by only 5  degrees C.
      It was also observed that [emim]OAc inhibited much less GH10 xylanase (TasXyn10A)
      than the studied GH11 xylanases. The K m of TasXyn10A increased 3.5-fold in 15 %
      [emim]OAc with xylan as the substrate, whereas the approximate level of V max was
      not altered. The inhibition of enzyme activity by [emim]OAc was lesser at higher
      substrate concentrations. Therefore, high solid concentrations in industrial
      conditions may mitigate the inhibition of enzyme activity by ionic liquids.
      Molecular docking experiments indicated that the [emim] cation has major binding
      sites near the catalytic residues but in lower amounts in GH10 than in GH11
      xylanases. Therefore, [emim] cation likely competes with the substrate when
      binding to the active site. The docking results indicated why the effect is lower
      in GH10.

PMID- 25074838
TI  - Risk of ESRD and death in patients with CKD not referred to a nephrologist: a 7
      year prospective study.
AB  - BACKGROUND AND OBJECTIVES: Rising prevalence of CKD requires active involvement
      of general practitioners to limit ESRD and mortality risk. However, the outcomes
      of patients with CKD exclusively managed by general practitioners are ill
      defined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We prospectively
      evaluated 30,326 adult patients with nondialysis CKD stages 1-5 who had never
      received consultation in tertiary nephrology care recruited from 700 general
      practitioner offices in Italy during 2002 and 2003. CKD stages were classified as
      stages 1 and 2 (GFR >= 60 ml/min per 1.73 m(2) and either albuminuria or an
      International Classification of Diseases, Ninth Revision, Clinical Modification
      code for kidney disease), stage 3a (GFR=59-45), stage 3b (GFR=44-30), stage 4
      (GFR=29-15), and stage 5 (GFR<15). Primary outcome was the risk of ESRD (dialysis
      or transplantation) or all-cause death. RESULTS: Overall 64% of patients were in
      stage 3a, and 4.5% of patients were in stages 3b-5. Patients with stages 1 and 2
      were younger, were predominantly men, more frequently had diabetes, and had lower
      prevalence of previous cardiovascular disease than patients with stages 3a-5.
      Hypertension was frequent in all CKD stages (80%-94%), whereas there was a lower
      prevalence of dyslipidemia, albuminuria, and obesity associated with more
      advanced CKD. During the follow-up (median=7.2 years; interquartile range=4.7
      7.7), 6592 patients died and 295 started ESRD. Compared with stages 1 and 2
      (reference), mortality risk (hazard ratio, 95% confidence interval) was higher in
      stages 3b-5 (1.66, 1.49-1.86, 2.75, 2.41-3.13 and 2.54, 2.01-3.22, respectively)
      but not stage 3a (1.11, 0.99-1.23). Similarly, ESRD risk (hazard ratio, 95%
      confidence interval) was not higher at stage 3a (1.44, 0.79-2.64) but was greater
      in stages 3b-5 (11.0, 6.3-19.5, 91.2, 53.2-156.2 and, 122.8, 67.9-222.0,
      respectively). Among modifiable risk factors, anemia and albuminuria
      significantly predicted either outcome, whereas hypertension only predicted
      mortality. CONCLUSIONS: In patients with CKD not referred to nephrology, risks of
      ESRD and mortality were higher in those with CKD stages 3b-5.

PMID- 25074840
TI  - Successful treatment with plasma exchange for ANCA-negative pauci-immune
      crescentic glomerulonephritis with D-negative hemolytic uremic syndrome.
AB  - Co-existence of antineutrophil cytoplasmic antibody (ANCA)-negative pauci-immune
      crescentic glomerulonephritis (CGN) and thrombotic thrombocytopenic purpura
      hemolytic uremic syndrome (TTPHUS) is extremely rare and has a poor renal
      prognosis. We report a 76-year-old female that had both ANCA and anti-human
      lysosomal membrane protein 2 (LAMP-2) antibody-negative pauci-immune CGN with D
      negative HUS. She was admitted with proteinuria and worsening renal failure with
      massive crescent formation on renal biopsy specimens. We initiated intravenous
      methylprednisolone pulse therapy followed by oral prednisolone, but she still
      developed D-negative HUS. We then initiated plasma exchange, which achieved
      remission of D-negative HUS and improved renal function. To our knowledge, this
      is the first report of recovery from renal failure in ANCA-negative pauci-immune
      CGN with TTP-HUS.

PMID- 25074839
TI  - Comparative associations of muscle mass and muscle strength with mortality in
      dialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Reduced muscle mass and strength are prevalent
      conditions in dialysis patients. However, muscle strength and muscle mass are not
      congruent; muscle strength can diminish even though muscle mass is maintained or
      increased. This study addresses phenotype and mortality associations of these
      muscle dysfunction entities alone or in combination (i.e., concurrent loss of
      muscle mass and strength/mobility, here defined as sarcopenia). DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This study included 330 incident dialysis patients
      (203 men, mean age 53+/-13 years, and mean GFR 7+/-2 ml/min per 1.73 m(2))
      recruited between 1994 and 2010 and followed prospectively for up to 5 years. Low
      muscle mass (by dual-energy x-ray absorptiometry appendicular mass index) and low
      muscle strength (by handgrip) were defined against young reference populations
      according to the European Working Group on Sarcopenia in Older People. RESULTS:
      Whereas 20% of patients had sarcopenia, low muscle mass and low muscle strength
      alone were observed in a further 24% and 15% of patients, respectively. Old age,
      comorbidities, protein-energy wasting, physical inactivity, low albumin, and
      inflammation associated with low muscle strength, but not with low muscle mass
      (multivariate ANOVA interactions). During follow-up, 95 patients (29%) died and
      both conditions associated with mortality as separate entities. When combined,
      individuals with low muscle mass alone were not at increased risk of mortality
      (adjusted hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 0.56 to
      2.67). Individuals with low muscle strength were at increased risk, irrespective
      of their muscle stores being appropriate (HR, 1.98; 95% CI, 1.01 to 3.87) or low
      (HR, 1.93; 95% CI, 1.01 to 3.71). CONCLUSIONS: Low muscle strength was more
      strongly associated with aging, protein-energy wasting, physical inactivity,
      inflammation, and mortality than low muscle mass. Assessment of muscle
      functionality may provide additional diagnostic and prognostic information to
      muscle-mass evaluation.

PMID- 25074841
TI  - Osteoid osteoma of the distal pole of the scaphoid mimicking flexor carpi
      radialis tendinitis.

PMID- 25074842
TI  - Career development for early career academics: benefits of networking and the
      role of professional societies.
AB  - Whilst effective networking is vitally important for early career academics,
      understanding and establishing useful networks is challenging. This paper
      provides an overview of the benefits and challenges of networking in the academic
      field, particularly for early career academics, and reflects on the role of
      professional societies in facilitating networking. 

PMID- 25074843
TI  - Cognition and the risk of eating disorders in Spanish adolescents: the AVENA and
      AFINOS studies.
AB  - Eating disorders (ED) can arise from a combination of biological and
      psychological factors. Some studies suggest that intellectual factors might be
      important in the development of ED, although the evidence is still scarce. The
      aim of this study was to examine the association between cognition measurements
      (cognitive performance and academic achievement) and the risk of developing ED in
      adolescents considering their weight status. The sample consisted of 3,307
      adolescents (1,756 girls), aged 13-18.5 years, who participated in the AVENA (n =
      1,430; 783 girls) and AFINOS (n = 1,877; 973 girls) studies. Cognitive
      performance was measured by the TEA test in the AVENA study, and academic
      achievement was self-reported in the AFINOS study. ED risk was evaluated in both
      studies by using the SCOFF questionnaire. Body mass index was calculated to
      classify adolescents as non-overweight or overweight (including obesity).
      Overweight adolescents showed a higher risk of developing ED than non-overweight
      ones in both studies. In the AVENA study, overweight boys with low performance in
      reasoning ability showed increased risk of ED (p = 0.05). In the AFINOS study,
      overweight boys with low academic performance in physical education and non
      overweight girls with low academic achievement in all the areas analyzed showed
      higher risk of ED than their peers (all p < 0.05). CONCLUSION: No association
      between cognitive performance and ED risk was found in adolescents, while
      academic achievement was associated with ED risk, especially in non-overweight
      girls. The non-cognitive traits that accompany academic achievement could
      influence the likelihood of developing ED in these girls.

PMID- 25074844
TI  - Halopenitus salinus sp. nov., isolated from the brine of salted brown alga
      Laminaria.
AB  - A halophilic archaeal strain, SKJ47(T), was isolated from a commercial
      preparation of the brown alga Laminaria produced at Dalian, Liaoning Province,
      China. Cells of the strain were observed to be short rods, stain Gram-negative,
      and to form red-pigmented colonies on solid media. Strain SKJ47(T) was found to
      be able to grow at 20-50  degrees C (optimum 37  degrees C), at 0.9-4.8 M NaCl
      (optimum 2.6-3.1 M), at pH 6.0-9.5 (optimum pH 7.0). The cells lysed in distilled
      water and the minimal NaCl concentration to prevent cell-lysis was found to be 5%
      (w/v). The major polar lipids of the strain were identified as
      phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester,
      phosphatidylglycerol sulfate and two glycolipids chromatographically identical to
      those of Halopenitus persicus IBRC 10041(T). The 16S rRNA gene and rpoB' gene of
      strain SKJ47(T) were found to be phylogenetically related to the corresponding
      genes of Halopenitus malekzadehii IBRC-M 10418(T) (96.3 and 91.9% nucleotide
      identity, respectively) and Hpt. persicus IBRC 10041(T) (96.2 and 93.8%). The DNA
      G+C content of strain SKJ47(T) was determined to be 65.0 mol%. The phenotypic,
      chemotaxonomic and phylogenetic properties suggested that strain SKJ47(T) (=CGMCC
      1.12229(T) = JCM 18641(T)) represents a new species of the genus Halopenitus, for
      which the name Halopenitus salinus sp. nov. is proposed.

PMID- 25074845
TI  - Tumor response assessment by measuring the single largest lesion per organ in
      patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: The criterion of two target lesions per organ in the RECIST 1.1 is an
      arbitrary one, not being supported by any objective evidence. We compared tumor
      responses, respectively, using the RECIST 1.1 (measuring two target lesions per
      organ) and modified RECIST 1.1 (measuring the single largest lesion in each
      organ) in patients with advanced non-small cell lung cancer (NSCLC). MATERIALS
      AND METHODS: We reviewed medical records of patients with advanced NSCLC who
      received a first-line chemotherapy between January 2004 and December 2013 and
      compared tumor responses according to the two criteria using computed tomography.
      RESULTS: A total of 64 patients who had at least two target lesions in any organ
      according to the RECIST 1.1 were included in the study. The differences in the
      percentage changes of the sum of tumor measurements between the RECIST 1.1 and
      mRECIST 1.1 were all within 10%. Thirty-three patients (51.6%) showed an increase
      in the absolute value of the percentage change when adopting the mRECIST 1.1,
      instead of the RECIST 1.1. The tumor responses showed high concordance between
      the two criteria (k=0.899). Only three patients (4.7%) showed disagreement of the
      responses between the RECIST 1.1 and mRECIST 1.1. The overall response rates
      (20.3% vs. 20.3%) and disease control rates (89.1% vs. 90.6%) of first-line
      chemotherapy were not significantly different between the two criteria.
      CONCLUSION: The modified RECIST 1.1 was comparable to the original RECIST 1.1 in
      the response assessment of patients with advanced NSCLC. Our result suggests that
      it may be possible to measure the single largest target lesion per organ for
      evaluation of the best tumor response.

PMID- 25074846
TI  - Who Opts out of the Statutory Health Insurance? A Discrete Time Hazard Model for
      Germany.
AB  - The coexistence of social health insurance and private health insurance in
      Germany is subject to intense public debate. As only few have the opportunity to
      choose between the two systems, they are often regarded as privileged by the
      health insurance system. Applying a hazard model in discrete time, this paper
      examines the role of incentives set by the regulatory framework and the influence
      of individual personality characteristics on the decision to opt out of the
      statutory system. To address potential endogeneity of one of the key explanatory
      variables, an instrumental variable approach is also applied. The estimation
      results yield robust evidence on the choice of health insurance type that is
      consistent with pragmatic decision making, with both incentives set by regulation
      and personality traits as relevant determinants. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 25074847
TI  - A semi-synthetic derivative of artemisinin, artesunate inhibits prostaglandin E2
      production in LPS/IFNgamma-activated BV2 microglia.
AB  - Artesunate is a semi-synthetic derivative of artemisinin used to treat malaria,
      and has been shown to possess anti-inflammatory activity. In this study, we have
      investigated the effect of artesunate on PGE2 production/COX-2 protein expression
      in LPS+IFNgamma-activated BV2 microglia. To further understand the mechanism of
      action of this compound, we investigated its interference with NF-kappaB and p38
      MAPK signalling pathways. PGE2 production was determined using EIA, while protein
      expressions of inflammatory targets like COX-2, mPGES-1, IkappaB, p38 and
      MAPKAPK2 were evaluated using western blot. An NF-kappaB-bearing luciferase
      reporter gene assay was used to test the effect of artesunate on NF-kappaB
      mediated pro-inflammatory gene expression in HEK293 cells stimulated with
      TNFalpha (1ng/ml). Artesunate (2 and 4MUM), significantly (p <0.01) suppressed
      PGE2 production in LPS+IFNgamma-activated BV2 microglia. This effect was found to
      be mediated via reduction in COX-2 and mPGES-1 proteins. Artesunate also produced
      significant inhibition of TNFalpha and IL-6 production in activated BV2
      microglia. Further investigations showed that artesunate (0.5-4MUM) significantly
      (p <0.001) reduced NF-kappaB-driven luciferase expression, and inhibited IkappaB
      phosphorylation and degradation, through inhibition of IKK. Artesunate inhibited
      phosphorylation of p38 MAPK and its substrate MAPKAPK2 following stimulation of
      microglia with LPS+IFNgamma. Taken together, we have shown that artesunate
      prevents neuroinflammation in BV2 microglia by interfering with NF-kappaB and p38
      MAPK signalling. 

PMID- 25074848
TI  - Synthesis and biological evaluation of new simple indolic non peptidic HIV
      Protease inhibitors: the effect of different substitution patterns.
AB  - New structurally simple indolic non peptidic HIV Protease inhibitors were
      synthesized from (S)-glycidol by regioselective methods. Following the concept of
      targeting the protein backbone, different substitution patterns were introduced
      onto the common stereodefined isopropanolamine core modifying the type of
      functional group on the indole, the position of the functional group on the
      indole and the type of the nitrogen containing group (sulfonamides or
      perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition
      activity of such compounds confirmed the general beneficial effect of the 5
      indolyl substituents in presence of arylsulfonamide moieties, which furnished
      activities in the micromolar range. Preliminary docking analysis allowed to
      identify several key features of the binding mode of such compounds to the
      protease. 

PMID- 25074849
TI  - European College of Orthodontics: Commission of affiliation and titularisation.
      Case No.: 13021.
AB  - Date of birth: 23/06/1996; sex: female. A. PRETREATMENT RECORDS: (06/2009; 13
      years). DIAGNOSIS: Normodivergence of the bony bases; skeletal class I; angle
      class I; tooth size-arch length discrepancy. TREATMENT: Extraction of 15-25-35
      45; maxillary and mandibular multi-bracket appliance. B. END OF TREATMENT
      RECORDS: (06/2011; 15 years). RETENTION: Maxilla: palatal wire bonded 12 to 22;
      mandible: lingual wire bonded 33 to 43. C. END OF RETENTION RECORDS: (9/2011;
      15.3 years).

PMID- 25074851
TI  - The influence of the 'patient-to-patient model' on swallowing problems in
      patients with supraglottic laryngeal cancer.
AB  - AIMS: To evaluate the patient-to-patient model and swallowing problems in Chinese
      patients with supraglottic laryngeal cancer (SLC), and to find a solution to help
      SLC patients with swallowing problems. METHODS: Eighty-nine patients who had
      undergone operation for horizontal partial laryngectomy were chosen and divided
      randomly into two groups. The European Organization for Research and Treatment of
      Cancer (EORTC), Swallow Quality-of-Life (SWAL-QOL) and Visual Analogue Scale
      (VAS) questionnaires were used to measure the quality of life and swallowing
      situation of those patients. RESULTS: At 0.5 and 1 months after eating, the
      scores of the EORTC QLQ-C30 and SWAL-QOL of the participant group were
      significantly higher than those of the nonparticipant group (p < 0.05). One week
      after eating, the VAS score for swallowing improved significantly from 4.9 to 7.9
      in the participant group. However, in the nonparticipant group, the VAS score
      showed no obvious change (from 4.5 to 4.1). CONCLUSIONS: We concluded that the
      patient-to-patient model may be utilized in clinical cases to solve swallowing
      problems of SLC patients, and infered that swallowing problems mainly appeared in
      60 to 70-year-olds, and 1 week after eating was a critical time point of
      communication.

PMID- 25074852
TI  - Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats.
AB  - Oxidative stress has been shown to play an important role in the pathogenesis of
      diabetes-induced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic
      compound, a main metabolite of anthocyanin, which has been reported to display
      various pharmacological properties. We proposed the hypothesis that PCA exerts
      cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague
      Dawley rats by a single i.p. injection of 50 mg/kg streptozotocin (STZ) and
      groups of these animals received the following treatments for 12 weeks: i) oral
      administration of vehicle, ii) oral administration of PCA at a dose of 50  mg/kg
      per day, iii) oral administration of PCA at a dose of 100 mg/kg per day, iv) s.c.
      injection of insulin at a dose of 4 U/kg per day, and v) a combination of PCA,
      100 mg/kg per day and insulin, 4 U/kg per day. Metabolic parameters, results from
      echocardiography, and heart rate variability were monitored every 4 weeks, and
      the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and
      cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin,
      and combined drug treatments significantly improved metabolic parameters and
      cardiac function as shown by increased percentage fractional shortening and
      percentage left ventricular ejection fraction and decreased low-frequency:high
      frequency ratio in T1DM rats. Moreover, all treatments significantly decreased
      plasma HbA1c and cardiac MDA levels, improved cardiac mitochondrial function, and
      increased BCL2 expression. Our results demonstrated for the first time, to our
      knowledge, the efficacy of PCA in improving cardiac function and cardiac
      autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing
      anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential
      cardioprotective effect and could restore cardiac function when combined with
      insulin treatment. These findings indicated that supplementation with PCA might
      be helpful for the prevention and alleviation of cardiovascular complications in
      T1DM. 

PMID- 25074853
TI  - Direct stimulation of bone mass by increased GH signalling in the osteoblasts of
      Socs2-/- mice.
AB  - The suppressor of cytokine signalling (Socs2(-/-))-knockout mouse is
      characterised by an overgrowth phenotype due to enhanced GH signalling. The
      objective of this study was to define the Socs2(-/-) bone phenotype and determine
      whether GH promotes bone mass via IGF1-dependent mechanisms. Despite no elevation
      in systemic IGF1 levels, increased body weight in 4-week-old Socs2(-/-) mice
      following GH treatment was associated with increased cortical bone area (Ct.Ar)
      (P<0.01). Furthermore, detailed bone analysis of male and female juvenile and
      adult Socs2(-/-) mice revealed an altered cortical and trabecular phenotype
      consistent with the known anabolic effects of GH. Indeed, male Socs2(-/-) mice
      had increased Ct.Ar (P<0.05) and thickness associated with increased strength.
      Despite this, there was no elevation in hepatic Igf1 expression, suggesting that
      the anabolic bone phenotype was the result of increased local GH action.
      Mechanistic studies showed that in osteoblasts and bone of Socs2(-/-) mice, STAT5
      phosphorylation was significantly increased in response to GH. Conversely,
      overexpression of SOCS2 decreased GH-induced STAT5 signalling. Although an
      increase in Igf1 expression was observed in Socs2(-/-) osteoblasts following GH,
      it was not evident in vivo. Igf1 expression levels were not elevated in response
      to GH in 4-week-old mice and no alterations in expression was observed in bone
      samples of 6-week-old Socs2(-/-) mice. These studies emphasise the critical role
      of SOCS2 in controlling the local GH anabolic bone effects. We provide compelling
      evidence implicating SOCS2 in the regulation of GH osteoblast signalling and
      ultimately bone accrual, which maybe via mechanisms that are independent of IGF1
      production in vivo. 

PMID- 25074854
TI  - Virological efficacy of abacavir: systematic review and meta-analysis.
AB  - OBJECTIVES: The efficacy of abacavir/lamivudine has been reported to be inferior
      to tenofovir/emtricitabine. Several randomized clinical trials (RCTs)
      investigated the effectiveness and safety of abacavir/lamivudine and
      tenofovir/emtricitabine combined antiretroviral treatment (cART) and we have
      reviewed the available evidence. DESIGN: Systematic review and meta-analysis of
      RCTs using standard Cochrane Collaboration methodologies. METHODS: We calculated
      risk ratios (RRs) with 95% CIs. The primary outcome was the rate of patients with
      viral load (VL) below the pre-defined cut-off at 48 weeks and/or at 96 weeks.
      Where available, results were analysed according to VL screening levels (<100,000
      or >100,000 copies/mL) with conventional meta-analytical pooling by subgroups and
      meta-regression. RESULTS: Meta-analytical pooling of RCTs with a direct
      comparison of abacavir/lamivudine and tenofovir/emtricitabine according to
      baseline VL at 48 weeks (six trials, 4118 patients) showed that the proportions
      of subjects with VL <50 copies/mL were similar in the overall comparison (RR
      0.98; 95% CI 0.94-1.03), in the low baseline VL strata (RR 1.01; 95% CI 0.99
      1.03) and in the high baseline VL strata (RR 0.96; 95% CI 0.90-1.03). Meta
      regression analysis at 48 weeks confirms the results of subgroup analysis.
      Similar virological results were found at 96 weeks (four trials, 2003 patients).
      Differences in the occurrence of adverse events requiring discontinuation of
      treatment favoured tenofovir recipients (RR 1.26; 95% CI 0.99-1.61), but this
      difference, mostly related to suspected abacavir hypersensitivity reaction, was
      not statistically significant. CONCLUSIONS: Our cumulative, cross-sectional data
      suggest a similar virological efficacy of abacavir/lamivudine and
      tenofovir/emtricitabine regardless of the baseline VL.

PMID- 25074855
TI  - Evaluation of gidB alterations responsible for streptomycin resistance in
      Mycobacterium tuberculosis.
AB  - OBJECTIVES: To evaluate gidB alterations for possible impact on the cumulative
      mechanism underlying the acquisition of high-level streptomycin resistance in
      Mycobacterium tuberculosis. METHODS: Fifty-two isolates with high streptomycin
      resistance and 23 isolates with low streptomycin resistance were sequenced for
      mutational analysis in the rpsL, rrs and gidB region. As the gidB protein has a
      complex substrate and no activity assay has yet been formulated, mutants of
      interest were subjected to in silico modelling and were structurally mapped
      together with active-site amino acid residues for assessment of the relevance to
      activity of the mutations found. RESULTS: Eight novel sense mutations and four
      novel mis-sense mutations in gidB were identified. Findings showed that active
      site morphology is not only greatly affected by mutants lying in close proximity
      to the active-site pocket, but also by other mutations altering secondary
      structure motifs and having an overall effect on protein structure. CONCLUSIONS:
      We conclude that gidB mutations address many unanswered questions and explain the
      whole story behind phenotypic streptomycin-resistant strains exhibiting no
      mutation in rpsL or rrs. They also validate the hypothesis of sequential
      progression of resistance from low to high due to the existence of gidB
      alterations in the genetic background.

PMID- 25074856
TI  - Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in
      Clostridium difficile infections: a meta-analysis and indirect treatment
      comparison.
AB  - OBJECTIVES: To evaluate the efficacy of fidaxomicin treatment, which has a
      limited effect on the normal gut flora, compared with vancomycin and
      metronidazole treatment in Clostridium difficile infections (CDIs). METHODS: A
      systematic literature review was conducted in July to August 2011 and updated in
      July 2013. For fidaxomicin versus vancomycin, efficacy was evaluated using meta
      analysis of data from two Phase III direct comparative studies (n = 1164). As
      there were no studies comparing fidaxomicin and metronidazole, an indirect
      comparison was made using data from three vancomycin versus metronidazole studies
      (n = 345), using the methodology of Bucher et al. (J Clin Epidemiol 1997; 50: 683
      91). This provides an OR for the indirect comparison of fidaxomicin versus
      metronidazole when direct evidence of fidaxomicin versus vancomycin and
      vancomycin versus metronidazole is available. RESULTS: Clinical cure rates were
      similar for fidaxomicin and vancomycin; the OR (95% CI) was 1.17 (0.82, 1.66).
      Recurrence [0.47 (0.34, 0.65)] was significantly lower and sustained cure rates
      [1.75 (1.35, 2.27)] significantly higher for fidaxomicin than vancomycin. Similar
      results were obtained in patient subgroups with severe CDI and with non-severe
      CDI. From the indirect comparison, the likelihood of recurrence [0.42 (0.18,
      0.96)] and sustained cure [2.55 (1.44, 4.51)] were significantly improved for
      fidaxomicin versus metronidazole. Again, similar results were obtained in those
      with severe and non-severe CDI. CONCLUSIONS: Fidaxomicin provides improved
      sustained cure rates in patients with CDI compared with vancomycin. An indirect
      comparison indicates that the same is also true for fidaxomicin versus
      metronidazole. In view of these data, fidaxomicin may be considered as first-line
      therapy for CDI.

PMID- 25074857
TI  - blaCTX-M-15-carrying Escherichia coli and Salmonella isolates from livestock and
      food in Germany.
AB  - OBJECTIVES: The characterization of CTX-M-15 beta-lactamase-producing Escherichia
      coli and Salmonella isolates originating mainly from German livestock and food.
      METHODS: E. coli (526, mainly commensals) and Salmonella (151) non-human isolates
      resistant to third-generation cephalosporins, originating from routine and
      monitoring submissions (2003-12) to the Federal Institute for Risk Assessment and
      different national targeted studies (2011-12), were examined for the presence of
      blaCTX-M-15 genes by PCR amplification/sequencing. Additional resistance and
      virulence genes were screened by DNA microarray and PCR amplification. E. coli
      isolates with blaCTX-M-15 were characterized by phylogenetic grouping, PFGE and
      multilocus sequence typing (MLST). The blaCTX-M-15 plasmids were analysed by
      replicon typing, plasmid MLST, S1 nuclease PFGE and Southern blot hybridization
      experiments. RESULTS: Twenty-one E. coli (livestock, food and a toy; 4.0%) and
      two Salmonella (horse and swine; 1.3%) isolates were CTX-M-15 producers. E. coli
      isolates were mainly ascribed to three clonal lineages of sequence types ST678
      (German outbreak with enteroaggregative Shiga-toxin-producing E. coli O104:H4;
      salmon, cucumber and a toy), ST410 (poultry, swine and cattle farms) and
      ST167/617 (swine farms and turkey meat). The blaCTX-M-15 genes were located on
      IncI1 and multireplicon IncF plasmids or on the chromosome of E. coli ST410
      isolates. CONCLUSIONS: The prevalence of CTX-M-15-producing isolates from non
      human sources in Germany is still low. The blaCTX-M-15 gene is, however, present
      in multidrug-resistant E. coli clones with pathogenic potential in livestock and
      food. The maintenance of the blaCTX-M-15 gene due to chromosomal carriage is
      noteworthy. The possibility of an exchange of CTX-M-15-producing isolates or
      plasmids between livestock and humans (in both directions) deserves continuous
      surveillance.

PMID- 25074858
TI  - Severe vitamin A deficiency in a child presenting as xerophthalmia.

PMID- 25074860
TI  - How reliable are methods to assess xylem vulnerability to cavitation? The issue
      of 'open vessel' artifact in oaks.
AB  - Three methods are in widespread use to build vulnerability curves (VCs) to
      cavitation. The bench drying (BD) method is considered as a reference because
      embolism and xylem pressure are measured on large branches dehydrating in the
      air, in conditions similar to what happens in nature. Two other methods of
      embolism induction have been increasingly used. While the Cavitron (CA) uses
      centrifugal force to induce embolism, in the air injection (AI) method embolism
      is induced by forcing pressurized air to enter a stem segment. Recent studies
      have suggested that the AI and CA methods are inappropriate in long-vesselled
      species because they produce a very high-threshold xylem pressure for embolism
      (e.g., P50) compared with what is expected from (i) their ecophysiology in the
      field (native embolism, water potential and stomatal response to xylem pressure)
      and (ii) the P50 obtained with the BD method. However, other authors have argued
      that the CA and AI methods may be valid because they produce VCs similar to the
      BD method. In order to clarify this issue, we assessed VCs with the three above
      mentioned methods on the long-vesselled Quercus ilex L. We showed that the BD VC
      yielded threshold xylem pressure for embolism consistent with in situ
      measurements of native embolism, minimal water potential and stomatal
      conductance. We therefore concluded that the BD method provides a reliable
      estimate of the VC for this species. The CA method produced a very high P50
      (i.e., less negative) compared with the BD method, which is consistent with an
      artifact related to the vessel length. The VCs obtained with the AI method were
      highly variable, producing P50 ranging from -2 to -8.2 MPa. This wide variability
      was more related to differences in base diameter among samples than to
      differences in the length of samples. We concluded that this method is probably
      subject to an artifact linked to the distribution of vessel lengths within the
      sample. Overall, our results indicate that the CA and the AI should be used with
      extreme caution on long-vesselled species. Our results also highlight that
      several criteria may be helpful to assess the validity of a VC.

PMID- 25074859
TI  - Seasonal variations in photosynthesis, intrinsic water-use efficiency and stable
      isotope composition of poplar leaves in a short-rotation plantation.
AB  - Photosynthetic carbon assimilation and transpirational water loss play an
      important role in the yield and the carbon sequestration potential of bioenergy
      devoted cultures of fast-growing trees. For six poplar (Populus) genotypes in a
      short-rotation plantation, we observed significant seasonal and genotypic
      variation in photosynthetic parameters, intrinsic water-use efficiency (WUEi) and
      leaf stable isotope composition (delta13C and delta18O). The poplars maintained
      high photosynthetic rates (between 17.8 and 26.9 MUmol m(-2) s(-1) depending on
      genotypes) until late in the season, in line with their fast-growth habit.
      Seasonal fluctuations were mainly explained by variations in soil water
      availability and by stomatal limitation upon photosynthesis. Stomatal rather than
      biochemical limitation was confirmed by the constant intrinsic photosynthetic
      capacity (Vcmax) during the growing season, closely related to leaf nitrogen (N)
      content. Intrinsic water-use efficiency scaled negatively with carbon isotope
      discrimination (Delta13Cbl) and positively with the ratio between mesophyll
      diffusion conductance (gm) and stomatal conductance. The WUEi-Delta13Cbl
      relationship was partly influenced by gm. There was a trade-off between WUEi and
      photosynthetic N-use efficiency, but only when soil water availability was
      limiting. Our results suggest that seasonal fluctuations in relation to soil
      water availability should be accounted for in future modelling studies assessing
      the carbon sequestration potential and the water-use efficiency of woody energy
      crops.

PMID- 25074861
TI  - Ethics and disasters involving geriatric patients.

PMID- 25074862
TI  - Disaster triage--are you ready?

PMID- 25074863
TI  - Trauma nursing core course for non-emergency nurses.

PMID- 25074864
TI  - Identification of predictor parameters to determine agro-industrial compost
      suppressiveness against Fusarium oxysporum and Phytophthora capsici diseases in
      muskmelon and pepper seedlings.
AB  - BACKGROUND: The lack of reliable prediction tools for evaluation of the level and
      specificity of compost suppressiveness limits its application. In our study,
      different chemical, biological and microbiological parameters were used to
      evaluate their potential use as a predictor parameter for the suppressive effect
      of composts against Fusarium oxysporum f. sp. melonis (FOM) and Phytophthora
      capsici (P. capsici) in muskmelon and pepper seedlings respectively. Composts
      were obtained from artichoke sludge, chopped vineyard pruning waste and various
      agro-industrial wastes (C1: blanched artichokes; C2: garlic waste; C3: dry olive
      cake). RESULTS: Compost C3 proved to offer the highest level of resistance
      against FOM, and compost C2 the highest level of resistance against P. capsici.
      Analysis of phospholipid fatty acids isolated from compost revealed that the
      three composts showed different microbial community structures. Protease, NAGase
      and chitinase activities were significantly higher in compost C3, as was
      dehydrogenase activity in compost C2. CONCLUSION: The use of specific parameters
      such as general (dehydrogenase activity) and specific enzymatic activities
      (protease, NAGase and chitinase activities) may be useful to predict compost
      suppressiveness against both pathogens. The selection of raw materials for agro
      industrial composts is important in controlling Fusarium wilt and Phytophthora
      root rot.

PMID- 25074865
TI  - A novel finasteride 0.25% topical solution for androgenetic alopecia:
      pharmacokinetics and effects on plasma androgen levels in healthy male
      volunteers.
AB  - OBJECTIVE: Finasteride, a selective inhibitor of type 2 5-alpha reductase
      isoenzyme, inhibits the conversion of testosterone to dihydrotestosterone (DHT)
      and is indicated in the treatment of male androgenetic alopecia. The study
      objective was to evaluate a newly developed finasteride 0.25% topical solution in
      comparison to the marketed finasteride 1 mg tablet, with respect to finasteride
      pharmacokinetics and suppressive effects on plasma DHT. METHODS: 24 healthy men
      with androgenetic alopecia were randomized in a single center, open-label,
      parallel-group, exploratory study, and received either multiple scalp
      applications of the topical solution b.i.d. or oral doses of the reference tablet
      o.d. for 7 days. Plasma finasteride, testosterone and DHT concentrations were
      determined. RESULTS: After multiple doses, mean (+/- SD) finasteride C(max) and
      AUC(0-t) corresponded to 0.46 +/- 0.28 ng/mL and 6.64 +/- 7.50 ng/mL x h for the
      topical solution and to 6.86 +/- 1.78 ng/mL and 57.93 +/- 29.38 ng/mL x h for the
      tablet. Plasma DHT was reduced by ~ 68 - 75% with the topical solution and by ~
      62 - 72% with the tablet. No relevant changes occurred for plasma testosterone
      with either treatment. No clinically significant adverse events occurred.
      CONCLUSIONS: A strong and similar inhibition of plasma DHT was found after 1 week
      of treatment with the topical and tablet finasteride ormulations, albeit
      finasteride plasma exposure was significantly lower with the topical than with
      the oral product (p < 0.0001).

PMID- 25074866
TI  - Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity
      and response in Jordanian rheumatoid arthritis patients.
AB  - OBJECTIVES: Methotrexate (MTX) is the most commonly used disease-modifying
      antirheumatic drug for the treatment of rheumatoid arthritis (RA). Genetic
      polymorphisms of reduced folate carrier (RFC1 G80A) and multi-drug resistance-1
      (MDR1 C3435T) might affect MTX response and/or toxicity. The aim of this study
      was to find out if there is an association between those polymorphisms and MTX
      toxicity and/or response in Jordanian RA patients. METHOD: A genotyping approach
      was used to determine the studied polymorphisms in 159 RA patients. RESULTS:
      There was an association between RFC1 G80A and MDR1 C3435T polymorphisms with MTX
      toxicity. Patients with RFC1 80GG genotype were at higher risk for
      gastrointestinal toxicity (p = 0.036). Patients carrying at least one MDR1 3435T
      variant allele were at higher risk for MTX overall toxicity (p = 0.04),
      especially hepatotoxicity (p = 0.028). Furthermore, the distribution of RFC1 G80A
      polymorphism between males and females was significantly different. The variant
      genotype 80AA was found to be more in males than in females (60% vs. 31%) (p =
      0.011). CONCLUSIONS: Our results suggest that genetic polymorphisms in
      methotrexate transporters affect the toxicity but not the response of MTX
      treatment. Further studies should be performed to have more conclusive results.

PMID- 25074867
TI  - A novel therapeutic use of HFA-BDP metereddose inhaler for asthmatic patients
      with rhinosinusitis: Case series.
AB  - OBJECTIVE: Most asthmatics have been found to have rhinosinusitis (RS). Patients
      with ethmoid sinusitis, in particular, often suffer from an impaired sense of
      smell; this is clinically important and necessitates concurrent treatment for
      both asthma and RS. As a rational therapeutic strategy, we focused on a fine
      particle HFA-134abeclomethasone dipropionate (HFA-BDP) metered-dose inhaler.
      Because of its small size, the medication is still present in the exhaled breath
      after inhalation. METHODS: Five mild-to-moderate asthmatics with
      ethomoidpredominant sinusitis characterized by an impaired sense of smell and
      mild peripheral blood eosinophilia received a single-agent treatment with orally
      inhaled HFA-BDP which was then exhaled through the nose. In addition, the stained
      small particles were created by an ultrasonic nebulizer and flow image of them
      during oral inhalation and nasal exhalation was evaluated by using nasal
      endoscopy. RESULTS: After treatment, the sense of smell was restored in all cases
      with a concomitant improvement in sinusitis as confirmed by computerized
      tomography. In addition, amelioration of peripheral blood eosinophilia as well as
      small airway obstruction as indicated by pulmonary function tests was observed.
      Macroscopical imaging revealed that small particles flow toward olfactory cleft
      during both the inhalation and exhalation phases. CONCLUSION: We have presented 5
      cases of asthmatic patients with RS treated with a concurrent single therapy, HFA
      BDP exhaled through the nose (ETN). A clinical trial must be considered to
      establish this new therapeutic strategy based on the concept of "one airway, one
      disease."

PMID- 25074868
TI  - Tetrandrine induces apoptosis in gallbladder carcinoma in vitro.
AB  - OBJECTIVE: The aims of this study were to observe the apoptosis effects of
      tetrandrine on human gallbladder carcinoma cell line (SGC-996), and to explore
      its related mechanism. METHODS: First, the anti-proliferative activities of
      tetrandrine on SGC-996 cells were determined by using the MTT assays. Then, cell
      cycle changes were detected by flow cytometry analysis. The apoptosis of cells
      was detected by the annexin V/propidium iodide double-staining assay. Detection
      of mitochondrial membrane potential was used to validate the ability of
      tetrandrine on inducing apoptosis. Finally, the expressions of the apoptosis
      related proteins (caspase-3, PARP, Bcl-2, and Bax) were analyzed by western blot.
      Statistical analyses were performed using the Studenta??s t-test for comparison
      of the results obtained from cells with or without treatment of tetrandrine.
      RESULTS: The MTT assay revealed a significant inhibition of cell proliferation in
      a dose- and time-dependent manner. Cells treated with tetrandrine were arrested
      at the S phase, according to the flow cytometric analysis. Tetrandrine produced a
      dose-dependent increase in the apoptotic cell population compared with control
      cells. Tetrandrine can also affect mitochondrial function by changing the
      mitochondrial membrane potential. Furthermore, western blot assay demonstrated
      that the tetrandrine induced apoptosis in SGC-996 cells by regulating the ratio
      of Bcl-2/Bax and activating the expression of cleaved caspase-3. CONCLUSIONS: The
      results indicate that tetrandrine may be a potential agent for the treatment of
      gallbladder carcinoma.

PMID- 25074869
TI  - Intravenous proton pump inhibitors for stress ulcer prophylaxis in critically ill
      patients: determining statistical equivalence according to evidence-based
      methods.
AB  - BACKGROUND: Although intravenous proton pump inhibitors (PPIs) are considered at
      least as effective as H2-receptors antagonists for stress ulcer prophylaxis (SUP)
      in critically ill patients, there is no data on whether there is also the proof
      of no difference among these agents. METHODS: The clinical material was the same
      as that reported in previous meta-analyses and included all trials comparing
      intravenous PPIs vs. H2-receptor antagonists for SUP in critically ill patients.
      Our methodology was a combination of meta-analysis and equivalence testing based
      on confidence intervals (CIs). The end-point was the rate of overt bleeding. All
      PPIs evaluated in the included trials were separately studied. The equivalence
      margins were derived from power calculation data of the original trials. RESULTS:
      Our analysis involved 8 randomized trials for 851 patients. Two comparisons were
      made (pantoprazole vs. H2-receptor antagonists and omeprazole vs. H2-receptor
      antagonists). The following RDs were estimated: pantoprazole, RD = -1.2%, 95% CI:
      -3.5% to +1.2%; omeprazole, RD = -3.0%, 95% CI: -7.2% to +1.3%. The 95% CIs
      confidence intervals for RDs remained within the +/- 6% margin. These results
      indicate that intravenous pantoprazole and intravenous omeprazole are equivalent,
      Conclusion: These two PPIs, when administered by intravenous route, are
      equivalent according to reasonable equivalence margins. This conclusion can be
      the basis to develop local acquisition tenders on these drugs. One advantage of
      this approach is that the feasibility of administrative decisions can directly be
      tested on clinical grounds and on the basis of standard evidence-based methods.

PMID- 25074870
TI  - Threonine-290 regulates nuclear translocation of the human pregnane X receptor
      through its phosphorylation/dephosphorylation by Ca2+/calmodulin-dependent
      protein kinase II and protein phosphatase 1.
AB  - The human pregnane X receptor (hPXR) is recognized as a xenobiotic-sensing
      nuclear receptor that transcriptionally regulates the gene expression of drug
      metabolizing enzymes and transporters. Our study elucidates the mechanism by
      which the localization of hPXR is regulated through threonine-290. A
      phosphomimetic mutation at threonine-290 (T290D) retained hPXR in the cytoplasm
      of HepG2, HuH6, and SW480 cells in vitro and the mouse liver in vivo even after
      treatment with rifampicin, and a phosphodeficient mutation (T290A) translocated
      from the cytoplasm to the nucleus as the wild-type hPXR. The amount of the
      unphosphorylated wild-type yellow fluorescent protein-hPXR fusion protein but not
      the T290A mutant increased on Phos-tag gels in response to stimulations with
      rifampicin and cyclin-dependent kinase 2 inhibitor roscovitine, and a marked
      increase was observed in the unphosphorylated levels of the T290A mutant in
      nontreated cells. The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      inhibitor KN93 [2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4
      chlorocinnamyl)-N-methylbenzylamine)] and transfection with anti-CaMKII small
      interfering RNA (siRNA) enhanced the unphosphorylated levels of the wild-type
      protein. CaMKII directly phosphorylated the threonine-290 of hPXR, and the T290A
      mutant conferred resistance to CaMKII. The protein phosphatase (PP) inhibitor
      okadaic acid (100 nM) and transfection with anti-PP1 siRNA but not anti-PP2A
      siRNA led to reduced expression of CYP3A4 mRNA. After the rifampicin and
      roscovitine stimulations, PP1 was recruited to the wild-type hPXR but not the
      T290A mutant. These results suggest that phosphorylation at threonine-290 by
      CaMKII may impair the function of hPXR by repressing its translocation to the
      nucleus, and dephosphorylation by PP1 is necessary for the xenobiotic-dependent
      nuclear translocation of hPXR. 

PMID- 25074871
TI  - Characterization of the active site properties of CYP4F12.
AB  - Cytochrome P450 4F12 is a drug-metabolizing enzyme that is primarily expressed in
      the liver, kidney, colon, small intestine, and heart. The properties of CYP4F12
      that may impart an increased catalytic selectivity (decreased promiscuity) were
      explored through in vitro metabolite elucidation, kinetic isotope effect
      experiments, and computational modeling of the CYP4F12 active site. By using
      astemizole as a probe substrate for CYP4F12 and CYP3A4, it was observed that
      although CYP4F12 favored astemizole O-demethylation as the primary route of
      metabolism, CYP3A4 was capable of metabolizing astemizole at multiple sites on
      the molecule. Deuteration of astemizole at the site of O-demethylation resulted
      in an isotope effect of 7.1 as well as an 8.3-fold decrease in the rate of
      clearance for astemizole by CYP4F12. Conversely, although an isotope effect of
      3.8 was observed for the formation of the O-desmethyl metabolite when deuterated
      astemizole was metabolized by CYP3A4, there was no decrease in the clearance of
      astemizole. Development of a homology model of CYP4F12 based on the crystal
      structure of cytochrome P450 BM3 predicted an active site volume for CYP4F12 that
      was approximately 76% of the active site volume of CYP3A4. As predicted, multiple
      favorable binding orientations were available for astemizole docked into the
      active site of CYP3A4, but only a single binding orientation with the site of O
      demethylation oriented toward the heme was identified for CYP4F12. Overall, it
      appears that although CYP4F12 may be capable of binding similar ligands to other
      cytochrome P450 enzymes such as CYP3A4, the ability to achieve catalytically
      favorable orientations may be inherently more difficult because of the increased
      steric constraints of the CYP4F12 active site. 

PMID- 25074872
TI  - Childhood-onset bullous systemic lupus erythematosus.
AB  - Bullous systemic lupus erythematosus has rarely been described in pediatric lupus
      population and the real prevalence of childhood-onset bullous systemic lupus
      erythematosus has not been reported. From January 1983 to November 2013, 303
      childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology
      Unit of the Childrens Institute of Hospital das Clinicas da Faculdade de Medicina
      Universidade da Universidade de Sao Paulo, three of them (1%) diagnosed as
      childhood-onset bullous systemic lupus erythematosus. All three cases presented
      tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with
      the median duration of 60 days (30-60). All patients fulfilled bullous systemic
      lupus erythematosus criteria. Two had nephritis and serositis and presented
      specific autoantibodies. The histological pattern demonstrated subepidermal
      blisters with neutrophils-predominant infiltrates within the upper dermis. Direct
      immunofluorescence (DIF) showed deposits of IgG and complement along the
      epidermal basement membrane, in the presence or absence of IgA and/or IgM. A
      positive indirect immunofluorescence on salt-split skin demonstrating dermal
      binding was observed in two cases. All of them had moderate/severe disease
      activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity
      Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with
      severe nephritis received immunosuppressive drugs. In conclusion, in the last 30
      years the prevalence of bullous lupus in childhood-onset lupus population was low
      (1%) in our tertiary University Hospital. A diagnosis of SLE should always be
      considered in children with recurrent tense vesiculobullous lesions with or
      without systemic manifestations. 

PMID- 25074873
TI  - Comparison of bone mass and quality determinants in adolescents and young adults
      with juvenile systemic lupus erythematosus (JSLE) and juvenile idiopathic
      arthritis (JIA).
AB  - BACKGROUND: Few prospective data have been published on the comparison of bone
      density and quality in homogeneous groups of patients with juvenile systemic
      lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA). OBJECTIVE AND
      HYPOTHESIS: The objective of this study is to perform a longitudinal evaluation
      of the prevalence and the characteristics of bone mass and quality and to
      evaluate the differences on the bone parameters, using DXA, pQCT and QUS.
      POPULATION AND/OR METHODS: Forty-three JSLE patients (35 females, 8 males, median
      age 18.8, range 14.0-34.1 years) have been studied with DXA, pQCT and QUS scans
      and compared with 138 JIA patients (112 females, 26 males, median age 18.9, range
      13.4-33.2 years), and 79 controls (59 females, 20 males; median age 19.3, range
      13.5-36.5 years). Of these, 39 patients (32 females and 7 males, median age 20.3,
      range 16.6-36.8 years) with JSLE were followed longitudinally and compared with
      131 patients (108 females, 23 males median age 20.7, range 15.8-37.1 years) with
      JIA and 63 controls (48 females, 15 males; median age 21.9, range 15.5-38.3
      years). RESULTS: JSLE patients have a higher bone cortical density (CrtBMD) than
      controls and JIA patients (p < 0.005). However, JSLE and JIA patients have a
      significantly reduced bone trabecular density (TrbBMD) compared to controls (p <
      0.0001), with no differences between JSLE and JIA. In addition, JIA patients show
      a significantly reduced muscle area (MuscleCSA) compared to JSLE and controls (p
      < 0.001). Conversely, fat area (FatCSA) is significantly increased both in JIA
      and JSLE patients when compared to controls (p < 0.001), with no differences
      between the JSLE and JIA groups. Analogous results are observed in the polar
      resistance to stress (SSIp). On longitudinal evaluation, contrary to CrtBMD, the
      difference between BMAD SDS, TrbBMD, MuscleCSA and FatCSA remains unchanged; in
      JSLE patients, SSIp is stable in comparison to JIA and controls without any
      difference between the two groups. CONCLUSIONS: The evaluation of bone density
      and structure parameters in JSLE patients highlights significant differences
      compared with JIA patients and controls. These data might indicate a different
      pathogenesis of bone damage in the two entities, and suggest a different
      diagnostic and therapeutic approach to improve the peak bone mass.

PMID- 25074875
TI  - Paraneoplastic dentate ganglionopathy: clinical and neuroimmunologic studies.
AB  - We describe the clinical and neuropathological features of two cases of
      cerebellar degeneration with selective involvement of the dentate nucleus. Both
      cases were associated with malignancy, however known paraneoplastic antibodies
      were absent. Pathological studies at autopsy confirmed T-cell-mediated neuronal
      destruction in the cerebellum which was strikingly limited to the dentate nucleus
      in both patients. The occurrence of these pathological features has not been
      previously described in antibodynegative paraneoplastic disease, but bears
      similarities to Rasmussena??s encephalitis. 

PMID- 25074874
TI  - Anaplastic chordoma with loss of INI1 and brachyury expression in a 2-year-old
      girl.

PMID- 25074876
TI  - Ganglioglioma in the bilateral ventricles arising from the septum and extending
      to the third ventricle.

PMID- 25074877
TI  - Is posterior reversible encephalopathy syndrome really reversible? Autopsy
      findings 4.5 years after radiographic resolution.
AB  - Posterior reversible encephalopathy syndrome (PRES) is defined by a spectrum of
      clinical symptoms and characteristic radiologic findings. Most patients show
      clinical recovery and normalization of imaging, even though a subset of rare
      cases may progress to cytotoxic edema, irreversible damage, and persistent
      radiological findings. As the condition is transient and seldom leads to death,
      few reports of pathologic findings during an acute episode or in patients
      following a resolved episode are available. Here, we describe the neuropathologic
      findings at autopsy in a 62-year-old woman with a history of systemic lupus
      erythematosus (SLE) and an episode of PRES that had resolved radiologically and
      clinically ~ 4.5 years prior to death. Autopsy findings included diffuse
      rarefaction of white matter with scattered microinfarcts, subpial gliosis, as
      well as perivascular lymphocytic aggregates and hemosiderin deposition in the
      sections from the posterior cerebrum. Some but not all of these changes of
      chronic white matter damage may be attributed to the coexisting systemic lupus
      erythematosus. Thus, we conclude that pathologic evidence of partial irreversible
      damage can be documented in PRES in spite of radiographic resolution of
      abnormalities. 

PMID- 25074879
TI  - Creation of a diagnostic wait times measurement framework based on evidence and
      consensus.
AB  - PURPOSE: Public reporting of wait times worldwide has to date focused largely on
      treatment wait times and is limited in its ability to capture earlier parts of
      the patient journey. The interval between suspicion and diagnosis or ruling out
      of cancer is a complex phase of the cancer journey. Diagnostic delays and
      inefficient use of diagnostic imaging procedures can result in poor patient
      outcomes, both physical and psychosocial. This study was designed to develop a
      framework that could be adopted for multiple disease sites across different
      jurisdictions to enable the measurement of diagnostic wait times and diagnostic
      delay. METHODS: Diagnostic benchmarks and targets in cancer systems were explored
      through a targeted literature review and jurisdictional scan. Cancer system
      leaders and clinicians were interviewed to validate the information found in the
      jurisdictional scan. An expert panel was assembled to review and, through a
      modified Delphi consensus process, provide feedback on a diagnostic wait times
      framework. RESULTS: The consensus process resulted in agreement on a measurement
      framework that identified suspicion, referral, diagnosis, and treatment as the
      main time points for measuring this critical phase of the patient journey.
      CONCLUSIONS: This work will help guide initiatives designed to improve patient
      access to health services by developing an evidence-based approach to
      standardization of the various waypoints during the diagnostic pathway. The
      diagnostic wait times measurement framework provides a yardstick to measure the
      performance of programs that are designed to manage and expedite care processes
      between referral and diagnosis or ruling out of cancer.

PMID- 25074880
TI  - Core concept: silicene.

PMID- 25074878
TI  - Comorbidity, chemotherapy toxicity, and outcomes among older women receiving
      adjuvant chemotherapy for breast cancer on a clinical trial: CALGB 49907 and
      CALGB 361004 (alliance).
AB  - PURPOSE: We evaluated associations among comorbidity, toxicity, time to relapse
      (TTR), and overall survival (OS) in older women with early-stage breast cancer
      receiving adjuvant chemotherapy. METHODS: Cancer and Leukemia Group B 49907
      (Alliance) randomly assigned women >= 65 years old with stages I-III breast
      cancer to standard adjuvant chemotherapy or capecitabine. We reviewed data from
      329 women who participated in the quality of life companion study CALGB 70103 and
      completed the Physical Health Subscale of the Older American Resources and
      Services Questionnaire. This questionnaire captures data on 14 comorbid
      conditions and the degree to which each interferes with daily activities. A
      comorbidity burden score was computed by multiplying the total number of
      conditions by each condition's level of interference with function. Outcomes were
      grade 3 to 5 toxicity, TTR, and OS. Logistic regression was used to evaluate
      associations between comorbidity and toxicity, and Cox proportional hazards
      models for TTR and survival. RESULTS: Number of comorbidities ranged from 0 to 10
      (median 2); the comorbidity burden score ranged from 0 to 25 (median 3). The most
      common conditions were arthritis (58%) and hypertension (55%). Comorbidity was
      associated with shorter OS, but not with toxicity or TTR. The hazard of death
      increased by 18% for each comorbidity (hazard ratio [HR] = 1.18, 95% CI = 1.06 to
      1.33) after adjusting for age, tumor size, treatment, node and receptor status.
      Comorbidity burden score was similarly associated with OS (HR = 1.08; 95% CI,
      1.03 to 1.14). CONCLUSIONS: Among older women enrolled onto a clinical trial,
      comorbidity was associated with shorter OS, but not toxicity or relapse.

PMID- 25074882
TI  - Three advantages of using traditional Chinese medicine to prevent and treat
      tumor.
AB  - Traditional Chinese medicine (TCM), an important component of complementary and
      alternative medicine, has evolved over thousands of years with its own unique
      system of theories, diagnostics and therapies. TCM has been increasingly used in
      the last decades and become well known for its significant role in preventing and
      treating cancer. We believe that TCM possesses advantages over Western medicine
      in specific aspects at a certain stage of cancer treatment. Here we summarize the
      advantages of TCM from three aspects: preventing tumorigenesis; attenuating
      toxicity and enhancing the treatment effect; and reducing tumor recurrence and
      metastasis. 

PMID- 25074883
TI  - Clinical and experimental studies on polyherbal formulations for diabetes:
      current status and future prospective.
AB  - Diabetes is a leading cause of morbidity and mortality in the world. There is
      currently an active search for antidiabetic drugs with greater effectiveness with
      fewer and less adverse side effects. Although numerous individual herbs have been
      experimentally or clinically reported to possess antidiabetic effects,
      considerably less research has been conducted on polyherbal compounds. It is
      believed that herbal compounds containing multiple plant products have
      synergistic antidiabetic effects and could enhance the desired actions. Several
      polyherbal formulations have been studied as therapeutic agents in diabetes
      management. To describe the current state of research on polyherbal compounds in
      the treatment of diabetes, an extensive review of literature was undertaken on
      several major databases. This paper presents what is known about the efficacy of
      these polyherbal formulations and compare their antidiabetic effects with those
      of current oral hypoglycemic drugs as reference. The percent decrease in blood
      glucose, lipids and other biochemical parameters achieved by each product in
      diabetic animals and patients is reported. Also, the possible mechanisms
      responsible for hypoglycemic action of polyherbal formulations are discussed. 

PMID- 25074884
TI  - Traditional Chinese medicinal herbs combined with epidermal growth factor
      receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)
      targeted treatment has been a standard therapy for advanced non-small cell lung
      cancer (NSCLC), but it is not tolerated well by all patients. In China, some
      studies have reported that traditional Chinese medicinal herbs (TCMHs) may
      increase efficacy and reduce toxicity when combined with EGFR-TKI, but outside of
      China few studies of this kind have been attempted. OBJECTIVE: This study is
      intended to systematically review the existing clinical evidence on TCMHs
      combined with EGFR-TKI for treatment of advanced NSCLC. SEARCH STRATEGY: PubMed,
      the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical
      Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web
      site of the American Society of Clinical Oncology (ASCO), the European Society
      for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were
      searched; the search included all documents published in English or Chinese
      before October 2013. INCLUSION CRITERIA: We selected randomized controlled trials
      based on specific criteria, the most important of which was that a TCMH plus EGFR
      TKI treatment group was compared with an EGFR-TKI control group in patients with
      advanced NSCLC. DATA EXTRACTION AND ANALYSIS: The modified Jadad scale was used
      to assess the quality of studies. For each included study, patient
      characteristics, treatment details, therapeutic approach and clinical outcomes
      were collected on a standardized form. When disagreements on study inclusion or
      data extracted from a study emerged, the consensus of all coauthors provided the
      resolution. The clinical outcome metrics consisted of objective response rate
      (ORR; complete response + partial response divided by the total number of
      patients), disease control rate (DCR; complete response + partial response + no
      change divided by the total number of patients), survival rate, improved or
      stabilized Karnofsky performance status (KPS), and severe toxicity. RevMan 5.0
      software was used for data syntheses and analyses. Risk ratio (RR) and 95%
      confidence interval (CI) were calculated; if the hypothesis of homogeneity was
      not rejected (P>0.1, I(2)<50%), the fixed-effect model was used to calculate the
      summary RR and the 95% CI. Otherwise, a random-effect model was used. RESULTS: In
      this review, 19 studies were included based on the selection criteria. Of them,
      13 studies were of high quality and 6 studies were of low quality, according to
      the modified Jadad scale. When the TCMH plus EGFR-TKI treatment groups were
      compared with the EGFR-TKI control groups the meta-analysis demonstrated a
      statistically significant higher ORR (RR 1.34; 95% CI 1.15 to 1.57; P=0.000 2),
      DCR (RR 1.18; 95% CI 1.09 to 1.27; P<0.000 1), one-year survival rate (RR 1.21;
      95% CI 1.01 to 1.44; P=0.04), 2-year survival rate (RR 1.91; 95% CI 1.26 to 2.89;
      P=0.002) and improved or stable KPS (RR 1.38; 95% CI 1.26 to 1.51; P<0.000 01).
      Severe toxicity for rash was decreased (RR 0.55; 95% CI 0.32 to 0.94; P=0.03), as
      were nausea and vomiting (RR 0.17; 95% CI 0.04 to 0.72; P=0.02) and diarrhea (RR
      0.46; 95% CI 0.24 to 0.89; P=0.02). Sensitivity analysis indicated that findings
      of the meta-analysis were robust to study quality. In the funnel plot analysis,
      asymmetry was observed, and publication bias was indicated by Egger's test
      (P=0.03). CONCLUSION: TCMH intervention can increase efficacy and reduce toxicity
      when combined with EGFR-TKI for advanced NSCLC, although this result requires
      further verification by more well designed studies.

PMID- 25074885
TI  - Effects of cinnamon on perineal pain and healing of episiotomy: a randomized
      placebo-controlled trial.
AB  - BACKGROUND: Analgesic and wound-healing effects of cinnamon, a widely used spice,
      have been shown in laboratory rats. However, we found no human studies in this
      area. OBJECTIVE: The aim of this study was to assess the effect of cinnamon on
      perineal pain and healing of episiotomy incision. DESIGN, SETTING, PARTICIPANTS
      AND INTERVENTIONS: In this double-blind, randomized, placebo-controlled trial,
      144 postpartum women were allocated into two groups, using stratified block
      randomization, 1 h after completion of episiotomy repair. They received cinnamon
      or placebo ointment, 2 mL every 12 h for 10 d. MAIN OUTCOME MEASURES: Perineal
      pain and wound healing were assessed using visual analogue scale (0-10) and
      Redness, Edema, Ecchymosis, Discharge, Approximation scale (0-15), respectively.
      General linear model was used to compare the groups on the outcomes adjusted for
      baseline values and stratified factors. RESULTS: Follow-up rate was 100% up to
      the 8 h time point in both groups, and 86% (62 of 72) in the cinnamon group and
      85% (61 of 72) in the placebo group at day 10-11 after delivery. Pain score in
      the cinnamon group was significantly lower than that in the placebo group at (4+/
      1) h (adjusted difference: -0.6, 95% confidence interval: -1.0 to -0.2) and (8+/
      1) h (-0.9, -1.4 to -0.3) after intervention, and on the 10-11th day after
      delivery (-1.4, -2.0 to -0.7). Also the cinnamon group showed significantly more
      improvement than the control group in healing score at (8+/-1) h (-0.2, -0.4 to 
      0.04) and the 10-11th day after delivery (-1.6, -2.0 to -1.1). CONCLUSION:
      Cinnamon can be used for reducing perineal pain and improving healing of
      episiotomy incision.

PMID- 25074886
TI  - Electrical response grading versus House-Brackmann scale for evaluation of facial
      nerve injury after Bell's palsy: a comparative study.
AB  - OBJECTIVE: There are no convenient techniques to evaluate the degree of facial
      nerve injury during a course of acupuncture treatment for Bell's palsy. Our
      previous studies found that observing the electrical response of specific facial
      muscles provided reasonable correlation with the prognosis of electroacupuncture
      treatment. Hence, we used the new method to evaluate the degree of facial nerve
      injury in patients with Bell's palsy in comparison with the House-Brackmann
      scale. The relationship between therapeutic effects and prognosis was analyzed to
      explore an objective method for evaluating Bell's palsy. METHODS: The facial
      nerve function of 68 patients with Bell's palsy was assessed with both electrical
      response grading and the House-Brackmann scale before treatment. Then differences
      in evaluation results of the two methods were compared. All enrolled patients
      received electroacupuncture treatment with disperse-dense wave at 1/100 Hz for 4
      weeks. After treatment, correlation analysis was conducted to find the
      relationship between electrical response and therapeutic effects or prognosis.
      RESULTS: Checking consistency between electrical response grading and House
      Brackmann scale: Kappa value 0.028 (P = 0.578). Correlation analysis: the two
      methods were correlated with the prognosis, and electrical response grading (rER
      = 0.789) was better than the House-Brackmann scale (rHB = 0.423). CONCLUSION:
      Electrical response grading is superior to the House-Brackmann scale in efficacy
      and reliability, and can conveniently assess the degree of facial nerve injury.
      The House-Brackmann scale is suitable for the patients with mild facial nerve
      injury, but its evaluation quality for severe facial nerve injury is poor.

PMID- 25074887
TI  - Evaluation of diuretic and laxative activity of hydro-alcoholic extract of
      Desmostachya bipinnata (L.) Stapf in rats.
AB  - OBJECTIVE: In continuation to the growing evidence for therapeutical potential of
      Desmostachya bipinnata (Linn) Stapf, the current pharmacological study was
      carried out to evaluate the diuretic and laxative activity of its hydro-alcoholic
      extract in rats. METHODS: The hydro-alcoholic extract of D. bipinnata whole plant
      was prepared by using Soxhlet extractor and subjected to analysis by standard
      preliminary phytochemical tests. Evaluation of both diuretic and laxative
      activity was carried out using standard methods as reported earlier. Frusemide
      (20 mg/kg) was served as positive control for diuretic activity and sennosides
      (10 mg/kg) served as negative control for laxative activity. RESULTS: The hydro
      alcoholic extract showed significant diuretic activity and was found to be the
      most potent in increasing the urinary output at 500 mg/kg when the effect was
      compared with that of the standard frusemide (P<0.01). Moreover, this extract was
      found to be most effective in increasing urinary electrolyte concentration
      (Na(+), K(+), and Cl(-)) at both doses tested. Whereas the results for laxative
      activity showed minimal increase of feces output at the dose of 500 mg/kg and the
      increase was negligible when compared with that of the standard drug sennosides.
      CONCLUSION: Altogether, the above significant findings validate and support its
      folkloric diuretic use and lend pharmacological credence to the ethno-medical use
      of this plant in traditional system of medicine, which demands further studies to
      investigate its active constituents, as well as its use and safety.

PMID- 25074888
TI  - Investigation of the nutraceutical potential of monofloral Indian mustard bee
      pollen.
AB  - OBJECTIVE: This study was designed to investigate the nutraceutical potential of
      monofloral Indian mustard bee pollen (MIMBP). METHODS: The nutritional value of
      MIMBP was examined in terms of proteins, fats, carbohydrates, and energy value.
      Its chemical composition in terms of total polyphenol and flavonoid content was
      determined. MIMBP was screened for free flavonoid aglycones by developing and
      validating a high-performance liquid chromatography-photo diode array (HPLC-PDA)
      method. MIMBP was analyzed for in vitro antioxidant effect in terms of 2,2
      diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. RESULTS: MIMBP was
      found to be comprised of proteins ((182.2+/-5.9) g/kg), fats ((137.7+/-6.8) g/kg)
      and carbohydrates ((560.6+/-17.4) g/kg), which result in its high energy value
      ((17 616.7+/-78.6) kJ/kg). MIMBP was found to contain polyphenols ((18 286.1+/
      374.0) mg gallic acid equivalent/kg) and flavonoids ((1 223.5+/-53.1) mg
      quercetin equivalent/kg). The HPLC-PDA analysis revealed the presence of
      kaempferol ((65.4+/-0.5) mg/kg) and quercetin ((51.4+/-0.4) mg/kg) in MIMBP,
      which can be used as markers for determining the quality of bee pollen. The MIMBP
      extract showed DPPH free radical-scavenging activity with a half maximal
      inhibitory concentration of 54.79 MUg/mL. CONCLUSION: The MIMBP was found to be a
      rich source of nutrients providing high caloric value, which makes it a candidate
      for a potential nutraceutical agent. The study also illustrated the high
      antioxidant content of MIMBP, especially in the principle polyphenols and
      flavonoids, which suggests its potential role in the prevention of free radical
      implicated diseases. The DPPH-scavenging effect of MIMBP further confirmed its
      antioxidant potential. Additionally, we developed a simple, specific and accurate
      HPLC-PDA method for the identification and quantification of free flavonoid
      aglycones. This can be applied in future screenings of the quality of pollen
      collected by honeybees.

PMID- 25074889
TI  - "Obamacare" covers fifty-four million Americans for acupuncture as Essential
      Healthcare Benefit.

PMID- 25074890
TI  - Introducing considerations in the Translation of Chinese Medicine.
AB  - This article introduces the document, Considerations in the Translation of
      Chinese Medicine, published in PDF form online in both Chinese and English. This
      20-page document includes several sections describing why the Considerations is
      necessary, the specificity of texts in Chinese medicine; the history of
      translation in Chinese medicine; who constitutes an ideal translator of Chinese
      medicine; what types of language exist in Chinese medicine; and specific issues
      in the translation of Chinese medicine, such as domestication versus
      foreignization, technical terminology, period-specific language, style, polysemy,
      and etymological translation. The final section offers a brief advisory for
      consumers, and concludes with a call to further discussion, and action,
      specifically in the development of international collaborative efforts towards
      the creation of more rigorous guidelines for the translation of Chinese medicine.
      The current article provides an overview of several of these sections, and
      includes links to the original document. 

PMID- 25074891
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      Diseases of Gynecology and Obstetrics (Part 2).

PMID- 25074892
TI  - Locomotion training using voluntary driven exoskeleton (HAL) in acute incomplete
      SCI.

PMID- 25074893
TI  - Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum
      disorders.

PMID- 25074894
TI  - Alcohol consumption and cognitive decline in early old age.

PMID- 25074896
TI  - Clinical reasoning: a woman with subacute progressive confusion and gait
      instability.

PMID- 25074895
TI  - Mystery case: giant mature teratoma of the lateral ventricle in a child.

PMID- 25074897
TI  - Teaching video neuroimages: lid lag sign and diplopia in paramyotonia congenita.

PMID- 25074898
TI  - Patient page. Racial differences and disability after stroke.

PMID- 25074899
TI  - Increased risk of human parvovirus B19 infection in day-care employees: a cohort
      study among pregnant workers during an epidemic in Finland.
AB  - BACKGROUND: Human parvovirus B19 (B19V) infection during early pregnancy
      increases the risk of miscarriage. Studies have inconsistently shown an elevated
      risk of infection among women with occupational contacts with children.
      Methodological differences, particularly in defining occupational exposure and in
      the type of reference group, may explain the conflicting findings. METHODS: This
      cohort study compared B19V infections in pregnant day-care employees and
      healthcare professionals during a B19V epidemic in Finland. Women were identified
      from the files of nationwide trade unions and the National Supervisory Authority
      for Welfare and Health. Early-pregnancy maternal B19V IgG was analysed in 3710
      women, and infections were defined as seroconversions after analysing in parallel
      the available umbilical cord blood samples of the 847 seronegative mothers.
      Independently of the serological status, the actual employment during pregnancy
      was assessed using registered information on employment history. RESULTS: B19V
      infections were more common among day-care employees (22/331, 6.6%), than among
      those working in healthcare (12/326, 3.7%). The adjusted HRs of B19V infection,
      using proportional hazard regression, was 2.63 (95% CI 1.27 to 5.46) among all
      women and 5.59 (95% CI 1.40 to 22.4) among nulliparous women. CONCLUSIONS: Day
      care employees are at an increased risk of B19V infection, which warrants
      preventive measures.

PMID- 25074901
TI  - The configural shape illusion.
AB  - A new illusion, called the configural shape illusion (CSI), is described in which
      the apparent shape of an object (the "target") is systematically distorted by the
      presence of an adjacent shape (the "inducer") that is distinct from, but
      perceptually grouped with, the target. The target is selectively elongated in a
      direction consistent with the extension of the larger configuration that includes
      both target and inducer. Experiments 1 and 2 show that the CSI magnitude varies
      systematically with factors known to influence grouping strength between
      configural elements, including proximity, good continuation, positional
      alignment, lightness similarity, hue similarity, and common fate. Experiments 3
      through 5 examine the influence of relative inducer size and target size on
      illusion magnitude. We suggest that the CSI is caused by edge assimilation
      modulated by similarity between the target and inducer arising from population
      coding of edge positions. This assimilation account fits well with previous
      explanations of one-dimensional illusions of linear extent (e.g., the Muller-Lyer
      and Baldwin illusions), which are extended to account for the present two
      dimensional illusion of shape. 

PMID- 25074900
TI  - Local masking in natural images: a database and analysis.
AB  - Studies of visual masking have provided a wide range of important insights into
      the processes involved in visual coding. However, very few of these studies have
      employed natural scenes as masks. Little is known on how the particular features
      found in natural scenes affect visual detection thresholds and how the results
      obtained using unnatural masks relate to the results obtained using natural
      masks. To address this issue, this paper describes a psychophysical study
      designed to obtain local contrast detection thresholds for a database of natural
      images. Via a three-alternative forced-choice experiment, we measured thresholds
      for detecting 3.7 cycles/ degrees  vertically oriented log-Gabor noise targets
      placed within an 85 * 85-pixels patch (1.9 degrees  patch) drawn from 30 natural
      images from the CSIQ image database (Larson & Chandler, Journal of Electronic
      Imaging, 2010). Thus, for each image, we obtained a masking map in which each
      entry in the map denotes the root mean squared contrast threshold for detecting
      the log-Gabor noise target at the corresponding spatial location in the image.
      From qualitative observations we found that detection thresholds were affected by
      several patch properties such as visual complexity, fineness of textures,
      sharpness, and overall luminance. Our quantitative analysis shows that except for
      the sharpness measure (correlation coefficient of 0.7), the other tested low
      level mask features showed a weak correlation (correlation coefficients less than
      or equal to 0.52) with the detection thresholds. Furthermore, we evaluated the
      performance of a computational contrast gain control model that performed fairly
      well with an average correlation coefficient of 0.79 in predicting the local
      contrast detection thresholds. We also describe specific choices of parameters
      for the gain control model. The objective of this database is to provide
      researchers with a large ground-truth dataset in order to further investigate the
      properties of the human visual system using natural masks. 

PMID- 25074902
TI  - Do surface reflectance properties and 3-D mesostructure influence the perception
      of lightness?
AB  - A series of experiments were conducted to assess how the reflectance properties
      and the complexity of surface "mesostructure" (small-scale 3-D relief) influence
      perceived lightness. Experiment 1 evaluated the role of surface relief and gloss
      on perceived lightness. For surfaces with visible mesostructure, lightness
      constancy was better for targets embedded in glossy than matte surfaces. The
      results for surfaces that lacked surface relief were qualitatively different than
      the 3-D surrounds, exhibiting abrupt steps in perceived lightness at points at
      which the targets transition from being increments to decrements. Experiments 2
      and 4 compared the matte and glossy 3-D surrounds to two control displays, which
      matched either pixel histograms or a phase-scrambled power spectrum,
      respectively. Although some improved lightness constancy was observed for the 3-D
      gloss display over the histogram-matched display, this benefit was not observed
      for phase-scrambled variants of these images with equated power spectrums. These
      results suggest that the improved lightness constancy observed with 3-D surfaces
      can be well explained by the distribution of contrast across space and scale,
      independently of explicit information about surface shading or specularity
      whereas the putatively "simpler" flat displays may evoke more complex midlevel
      representations similar to that evoked in conditions of transparency. 

PMID- 25074903
TI  - Why the long face? The importance of vertical image structure for biological
      "barcodes" underlying face recognition.
AB  - Humans are experts at face recognition. The mechanisms underlying this complex
      capacity are not fully understood. Recently, it has been proposed that face
      recognition is supported by a coarse-scale analysis of visual information
      contained in horizontal bands of contrast distributed along the vertical image
      axis-a biological facial "barcode" (Dakin & Watt, 2009). A critical prediction of
      the facial barcode hypothesis is that the distribution of image contrast along
      the vertical axis will be more important for face recognition than image
      distributions along the horizontal axis. Using a novel paradigm involving dynamic
      image distortions, a series of experiments are presented examining famous face
      recognition impairments from selectively disrupting image distributions along the
      vertical or horizontal image axes. Results show that disrupting the image
      distribution along the vertical image axis is more disruptive for recognition
      than matched distortions along the horizontal axis. Consistent with the facial
      barcode hypothesis, these results suggest that human face recognition relies
      disproportionately on appropriately scaled distributions of image contrast along
      the vertical image axis. 

PMID- 25074905
TI  - Degree of conversion of resin-based orthodontic bonding materials cured with
      single-wave or dual-wave LED light-curing units.
AB  - AIM: To evaluate the degree of conversion (DC) of orthodontic adhesives (RBOAs)
      cured with dual peak or single peak light-emitting diode (LED) light-curing units
      (LCUs). MATERIALS AND METHODS: Standardized samples of RBOAs, APCPlus, Opal(r)
      Bond(r) and LightBond(TM) were prepared (n = 3) and cured with one of two dual
      peak LCUs (bluephase(r) G2-Ivoclar-Vivadent or Valo-Ultradent) or a single peak
      control (bluephase(r) Ivoclar-Vivadent). The DC was determined using micro-Raman
      spectroscopy. The presence or absence of initiators other than camphorquinone was
      confirmed by high-performance liquid chromatography and nuclear magnetic
      resonance spectroscopy. Data were analysed using general linear model in Minitab
      15 (Minitab Inc., State College, PA, USA). RESULTS: There was no significant
      difference in DC between APCPlus, and Opal(r) Bond (confidence interval: -3.89-
      to 2.48); significant difference between APCPlus and LightBond(TM) (-18.55 to 
      12.18) and Opal(r) Bond and Lightbond(TM) (-17.85 to -11.48); no significant
      difference between bluephase (single peak) and dual peak LCUs, bluephase G2 (
      4.896 to 1.476) and Valo (-3.935 to 2.437) and between bluephase G2 and Valo (
      2.225 to 4.147). APCPlus and Opal(r) Bond showed higher DC values than
      LightBond(TM) (P<0.05). Lucirin(r) TPO was found only in Vit-l-escence.
      CONCLUSION: Lucirin(r) TPO was not identified in the three orthodontic adhesives.
      All three LCUs performed similarly with the orthodontic adhesives: orthodontic
      adhesive make had a greater effect on DC than the LCUs. It is strongly suggested
      that manufacturers of resin-based orthodontic materials test report whether or
      not dual peak LCUs should be used with their materials. Dual peak LED LCUs,
      though suitable in the majority of cases, may not be recommended for certain non
      Lucirin(r) TPO-containing materials.

PMID- 25074904
TI  - Ensemble crowd perception: a viewpoint-invariant mechanism to represent average
      crowd identity.
AB  - Individuals can rapidly and precisely judge the average of a set of similar
      items, including both low-level (Ariely, 2001) and high-level objects (Haberman &
      Whitney, 2007). However, to date, it is unclear whether ensemble perception is
      based on viewpoint-invariant object representations. Here, we tested this
      question by presenting participants with crowds of sequentially presented faces.
      The number of faces in each crowd and the viewpoint of each face varied from
      trial to trial. This design required participants to integrate information from
      multiple viewpoints into one ensemble percept. Participants reported the mean
      identity of crowds (e.g., family resemblance) using an adjustable, forward
      oriented test face. Our results showed that participants accurately perceived the
      mean crowd identity even when required to incorporate information across multiple
      face orientations. Control experiments showed that the precision of ensemble
      coding was not solely dependent on the length of time participants viewed the
      crowd. Moreover, control analyses demonstrated that observers did not simply
      sample a subset of faces in the crowd but rather integrated many faces into their
      estimates of average crowd identity. These results demonstrate that ensemble
      perception can operate at the highest levels of object recognition after 3-D
      viewpoint-invariant faces are represented. 

PMID- 25074906
TI  - Transient freezing behavior in photophobic responses of Euglena gracilis
      investigated in a microfluidic device.
AB  - We found that the transient freezing behavior in photophobic responses of Euglena
      gracilis is a good indicator of the metabolic status of the cells. The transient
      blue light photophobic responses of E. gracilis cells were investigated on-chip
      using a new measurement, 'trace momentum' (TM), to evaluate their swimming
      activity quantitatively in real time. When blue light of intensity >30 mW cm(-2)
      was repeatedly switched on and off, a large negative spike in the TM was observed
      at the onset of the 'blue-light-off' phase. Single-cell trace analysis at a blue
      light intensity of 40 mW cm(-2) showed that 48% (on average, n = 15) of tumbling
      Euglena cells ceased activity ('freezing') for 2-30 s at the onset of blue-light
      off before commencing forward motion in a straight line (termed 'straightforward
      swimming'), while 45% smoothly commenced straightforward swimming without delay.
      The proportion of freezing Euglena cells depended on the blue light intensity
      (only 20% at 20 mW cm(-2)). When the cells were stimulated by four blue light
      pulses at the higher intensity, without pre-exposure, the transient freezing
      behavior was more prominent but, on repeating the stimuli after an 80 min
      interval in red light, the same cells did not freeze. This shows that the
      metabolism of the cells had changed to anti-freezing during the interval. The
      relationship between the interval time with/without light irradiation and the
      blue light adaptation was elucidated experimentally. The origin of the freezing
      behavior is considered to be a shortage of a metabolic substance that promotes
      smooth switching of flagellum movement from in situ rotation mode to a
      straightforward swimming mode. 

PMID- 25074907
TI  - The remodeling of seedling development in response to long-term magnesium
      toxicity and regulation by ABA-DELLA signaling in Arabidopsis.
AB  - Little information is available about signaling response to magnesium toxicity
      (MgT) in plants. This study presents the first evidence that abscisic acid (ABA)
      and DELLA proteins participate in signaling response to long-term MgT in
      Arabidopsis thaliana (Landsberg erecta). Morphological, physiological, and
      molecular characteristics of a wild-type and two Arabidopsis mutants, ABA
      insensitive mutant abi1-1 and constitutive elevated GA response mutant quadruple
      DELLA (DELLA-Q: gai-t6 rga-t2 rgl1-1 rgl2-1) were monitored under MgT and normal
      magnesium conditions. Two weeks of MgT treatment strongly influenced the growth
      of young plants, but growth inhibition of the DELLA-Q and abi1-1 mutants was less
      than that of the wild-type plants. Exogenous ABA further inhibited the growth of
      the DELLA-Q mutants, similar to that of the wild-type. Both ABA and MgT also
      promoted DELLA protein RGA accumulation in the nuclei. Transcriptional analysis
      supported these results and revealed that a complex signaling network has
      responded to MgT in Arabidopsis. DELLA enhancement, which depends on ABI1,
      contributed to the remodeling growth and development of young seedlings. 

PMID- 25074908
TI  - Efficient plant male fertility depends on vegetative nuclear movement mediated by
      two families of plant outer nuclear membrane proteins.
AB  - Increasing evidence suggests that nuclear migration is important for eukaryotic
      development. Although nuclear migration is conserved in plants, its importance
      for plant development has not yet been established. The most extraordinary plant
      nuclear migration events involve plant fertilization, which is starkly different
      from that of animals. Instead of evolving self-propelled sperm cells (SCs),
      plants use pollen tubes to deliver SCs, in which the pollen vegetative nucleus
      (VN) and the SCs migrate as a unit toward the ovules, a fundamental but barely
      understood process. Here, we report that WPP domain-interacting proteins (WIPs)
      and their binding partners the WPP domain-interacting tail-anchored proteins
      (WITs) are essential for pollen nuclear migration. Loss-of-function mutations in
      WIT and/or WIP gene families resulted in impaired VN movement, inefficient SC
      delivery, and defects in pollen tube reception. WIPs are Klarsicht/ANC-1/Syne-1
      Homology (KASH) analogs in plants. KASH proteins are key players in animal
      nuclear migration. Thus, this study not only reveals an important nuclear
      migration mechanism in plant fertilization but also, suggests that similar
      nuclear migration machinery is conserved between plants and animals. 

PMID- 25074909
TI  - Origin of myofibroblasts in the fibrotic liver in mice.
AB  - Hepatic myofibroblasts are activated in response to chronic liver injury of any
      etiology to produce a fibrous scar. Despite extensive studies, the origin of
      myofibroblasts in different types of fibrotic liver diseases is unresolved. To
      identify distinct populations of myofibroblasts and quantify their contribution
      to hepatic fibrosis of two different etiologies, collagen-alpha1(I)-GFP mice were
      subjected to hepatotoxic (carbon tetrachloride; CCl4) or cholestatic (bile duct
      ligation; BDL) liver injury. All myofibroblasts were purified by flow cytometry
      of GFP(+) cells and then different subsets identified by phenotyping. Liver
      resident activated hepatic stellate cells (aHSCs) and activated portal
      fibroblasts (aPFs) are the major source (>95%) of fibrogenic myofibroblasts in
      these models of liver fibrosis in mice. As previously reported using other
      methodologies, hepatic stellate cells (HSCs) are the major source of
      myofibroblasts (>87%) in CCl4 liver injury. However, aPFs are a major source of
      myofibroblasts in cholestatic liver injury, contributing >70% of myofibroblasts
      at the onset of injury (5 d BDL). The relative contribution of aPFs decreases
      with progressive injury, as HSCs become activated and contribute to the
      myofibroblast population (14 and 20 d BDL). Unlike aHSCs, aPFs respond to
      stimulation with taurocholic acid and IL-25 by induction of collagen-alpha1(I)
      and IL-13, respectively. Furthermore, BDL-activated PFs express high levels of
      collagen type I and provide stimulatory signals to HSCs. Gene expression analysis
      identified several novel markers of aPFs, including a mesothelial-specific marker
      mesothelin. PFs may play a critical role in the pathogenesis of cholestatic liver
      fibrosis and, therefore, serve as an attractive target for antifibrotic therapy. 

PMID- 25074910
TI  - Structural and thermodynamic consequences of burial of an artificial ion pair in
      the hydrophobic interior of a protein.
AB  - An artificial charge pair buried in the hydrophobic core of staphylococcal
      nuclease was engineered by making the V23E and L36K substitutions. Buried
      individually, Glu-23 and Lys-36 both titrate with pKa values near 7. When buried
      together their pKa values appear to be normal. The ionizable moieties of the
      buried Glu-Lys pair are 2.6 A apart. The interaction between them at pH 7 is
      worth 5 kcal/mol. Despite this strong interaction, the buried Glu-Lys pair
      destabilizes the protein significantly because the apparent Coulomb interaction
      is sufficient to offset the dehydration of only one of the two buried charges.
      Save for minor reorganization of dipoles and water penetration consistent with
      the relatively high dielectric constant reported by the buried ion pair, there is
      no evidence that the presence of two charges in the hydrophobic interior of the
      protein induces any significant structural reorganization. The successful
      engineering of an artificial ion pair in a highly hydrophobic environment
      suggests that buried Glu-Lys pairs in dehydrated environments can be charged and
      that it is possible to engineer charge clusters that loosely resemble catalytic
      sites in a scaffold protein with high thermodynamic stability, without the need
      for specialized structural adaptations. 

PMID- 25074911
TI  - Strand-specific (asymmetric) contribution of phosphodiester linkages on RNA
      polymerase II transcriptional efficiency and fidelity.
AB  - Nonenzymatic RNA polymerization in early life is likely to introduce backbone
      heterogeneity with a mixture of 2'-5' and 3'-5' linkages. On the other hand,
      modern nucleic acids are dominantly composed of 3'-5' linkages. RNA polymerase II
      (pol II) is a key modern enzyme responsible for synthesizing 3'-5'-linked RNA
      with high fidelity. It is not clear how modern enzymes, such as pol II,
      selectively recognize 3'-5' linkages over 2'-5' linkages of nucleic acids. In
      this work, we systematically investigated how phosphodiester linkages of nucleic
      acids govern pol II transcriptional efficiency and fidelity. Through dissecting
      the impacts of 2'-5' linkage mutants in the pol II catalytic site, we revealed
      that the presence of 2'-5' linkage in RNA primer only modestly reduces pol II
      transcriptional efficiency without affecting pol II transcriptional fidelity. In
      sharp contrast, the presence of 2'-5' linkage in DNA template leads to dramatic
      decreases in both transcriptional efficiency and fidelity. These distinct effects
      reveal that pol II has an asymmetric (strand-specific) recognition of
      phosphodiester linkage. Our results provided important insights into pol II
      transcriptional fidelity, suggesting essential contributions of phosphodiester
      linkage to pol II transcription. Finally, our results also provided important
      understanding on the molecular basis of nucleic acid recognition and genetic
      information transfer during molecular evolution. We suggest that the asymmetric
      recognition of phosphodiester linkage by modern nucleic acid enzymes likely stems
      from the distinct evolutionary pressures of template and primer strand in genetic
      information transfer during molecular evolution. 

PMID- 25074913
TI  - Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early
      B-cell development.
AB  - The immune system is influenced by the vital zinc (Zn) status, and Zn deficiency
      triggers lymphopenia; however, the mechanisms underlying Zn-mediated lymphocyte
      maintenance remain elusive. Here we investigated ZIP10, a Zn transporter
      expressed in the early B-cell developmental process. Genetic ablation of Zip10 in
      early B-cell stages resulted in significant reductions in B-cell populations, and
      the inducible deletion of Zip10 in pro-B cells increased the caspase activity in
      parallel with a decrease in intracellular Zn levels. Similarly, the depletion of
      intracellular Zn by a chemical chelator resulted in spontaneous caspase
      activation leading to cell death. Collectively, these findings indicated that
      ZIP10-mediated Zn homeostasis is essential for early B-cell survival. Moreover,
      we found that ZIP10 expression was regulated by JAK-STAT pathways, and its
      expression was correlated with STAT activation in human B-cell lymphoma,
      indicating that the JAK-STAT-ZIP10-Zn signaling axis influences the B-cell
      homeostasis. Our results establish a role of ZIP10 in cell survival during early
      B-cell development, and underscore the importance of Zn homeostasis in immune
      system maintenance. 

PMID- 25074914
TI  - Evolution of physiological responses to salt stress in hexaploid wheat.
AB  - Hexaploid bread wheat (Triticum aestivum L., genome BBAADD) is generally more
      salt tolerant than its tetraploid wheat progenitor (Triticum turgidum L.).
      However, little is known about the physiological basis of this trait or about the
      relative contributions of allohexaploidization and subsequent evolutionary
      genetic changes on the trait development. Here, we compared the salt tolerance of
      a synthetic allohexaploid wheat (neo-6x) with its tetraploid (T. turgidum; BBAA)
      and diploid (Aegilops tauschii; DD) parents, as well as a natural hexaploid bread
      wheat (nat-6x). We studied 92 morphophysiological traits and analyzed homeologous
      gene expression of a major salt-tolerance gene High-Affinity K(+) Transporter 1;5
      (HKT1;5). We observed that under salt stress, neo-6x exhibited higher fitness
      than both of its parental genotypes due to inheritance of favorable traits like
      higher germination rate from the 4x parent and the stronger root Na(+) retention
      capacity from the 2x parent. Moreover, expression of the D-subgenome HKT1;5
      homeolog, which is responsible for Na(+) removal from the xylem vessels, showed
      an immediate transcriptional reprogramming following allohexaploidization, i.e.,
      from constitutive high basal expression in Ae. tauschii (2x) to salt-induced
      expression in neo-6x. This phenomenon was also witnessed in the nat-6x. An
      integrated analysis of 92 traits showed that, under salt-stress conditions, neo
      6x resembled more closely the 2x than the 4x parent, suggesting that the salt
      stress induces enhanced expressivity of the D-subgenome homeologs in the
      synthetic hexaploid wheat. Collectively, the results suggest that condition
      dependent functionalization of the subgenomes might have contributed to the wide
      ranging adaptability of natural hexaploid wheat. 

PMID- 25074915
TI  - Structure-function analysis of mouse Sry reveals dual essential roles of the C
      terminal polyglutamine tract in sex determination.
AB  - The mammalian sex-determining factor SRY comprises a conserved high-mobility
      group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG
      box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ)
      tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is
      essential for male sex determination. To dissect the molecular functions of this
      domain, we generated a series of Sry mutants, and studied their biochemical
      properties in cell lines and transgenic mouse embryos. Sry protein lacking the
      polyQ domain was unstable, due to proteasomal degradation. Replacing this domain
      with irrelevant sequences stabilized the protein but failed to restore Sry's
      ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex
      determining function in vivo. These functions were restored only when a VP16
      transactivation domain was substituted. We conclude that the polyQ domain has
      important roles in protein stabilization and transcriptional activation, both of
      which are essential for male sex determination in mice. Our data disprove the
      hypothesis that the conserved HMG box domain is the only functional domain of
      Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel
      bifunctional module to activate Sox9 directly, whereas SRY proteins in other
      taxa, including humans, seem to lack this ability, presumably making them
      dependent on partner proteins(s) to provide this function. 

PMID- 25074916
TI  - Minicerebellum, now available for reductionists' functional study.

PMID- 25074917
TI  - Effective treatment of allergic airway inflammation with Helicobacter pylori
      immunomodulators requires BATF3-dependent dendritic cells and IL-10.
AB  - The prevalence of allergic asthma and other atopic diseases has reached epidemic
      proportions in large parts of the developed world. The gradual loss of the human
      indigenous microbiota has been held responsible for this trend. The bacterial
      pathogen Helicobacter pylori is a constituent of the normal gastric microbiota
      whose presence has been inversely linked to allergy and asthma in humans and
      experimental models. Here we show that oral or i.p. tolerization with H. pylori
      extract prevents the airway hyperresponsiveness, bronchoalveolar eosinophilia,
      pulmonary inflammation, and Th2 cytokine production that are hallmarks of
      allergen-induced asthma in mice. Asthma protection is not conferred by extracts
      from other enteropathogens and requires a heat-sensitive H. pylori component and
      the DC-intrinsic production of IL-10. The basic leucine zipper ATF-like 3 (BATF3)
      dependent CD103(+)CD11b(-) dendritic cell lineage is enriched in the lungs of
      protected mice and strictly required for protection. Two H. pylori persistence
      determinants, the gamma-glutamyl-transpeptidase GGT and the vacuolating cytotoxin
      VacA, are required and sufficient for asthma protection and can be administered
      in purified form to prevent asthma. In conclusion, we provide preclinical
      evidence for the concept that the immunomodulatory properties of H. pylori can be
      exploited for tolerization strategies aiming to prevent allergen-induced asthma. 

PMID- 25074919
TI  - Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell
      receptor signal strength.
AB  - The humoral immune response, also called the antibody-mediated immune response,
      is one of the main adaptive immune systems. The essential micronutrient zinc (Zn)
      is known to modulate adaptive immune responses, and dysregulated Zn homeostasis
      leads to immunodeficiency. However, the molecular mechanisms underlying this Zn
      mediated modulation are largely unknown. Here, we show that the Zn transporter
      SLC39A10/ZIP10 plays an important role in B-cell antigen receptor (BCR) signal
      transduction. Zip10-deficiency in mature B cells attenuated both T-cell-dependent
      and -independent immune responses in vivo. The Zip10-deficient mature B cells
      proliferated poorly in response to BCR cross-linking, as a result of dysregulated
      BCR signaling. The perturbed signaling was found to be triggered by a reduction
      in CD45R phosphatase activity and consequent hyperactivation of LYN, an essential
      protein kinase in BCR signaling. Our data suggest that ZIP10 functions as a
      positive regulator of CD45R to modulate the BCR signal strength, thereby setting
      a threshold for BCR signaling in humoral immune responses. 

PMID- 25074922
TI  - Effects of age, nursing, and oral IGF1 supplementation on neonatal porcine
      cervical development.
AB  - Nursing supports neonatal porcine uterine and testicular development, however,
      lactocrine effects on cervical development are undefined. Studies were conducted
      to determine the effects of i) age and the imposition of the lactocrine-null
      state from birth (postnatal day 0 (PND0)) by milk replacer feeding on cervical
      histology; ii) imposition of the lactocrine-null state for 2 days from birth on
      cervical cell proliferation, as reflected by proliferating cell nuclear antigen
      immunostaining; and iii) a single feeding of colostrum or milk replacer,
      administered at birth, with or without oral IGF1, on cervical cell proliferation
      and phosphorylated AKT (pAKT) and B-cell lymphoma 2 (BCL2) protein levels at 12 h
      postnatal. Cervical crypt depth and height of luminal epithelium (LE) increased
      with age by PND14, when both responses were reduced in replacer-fed gilts. Cell
      proliferation was reduced in LE at PND2, and in crypt epithelium and stroma by
      PND14 in replacer-fed gilts. Returning replacer-fed gilts to nursing on PND2 did
      not rescue the cervical phenotype by PND14. A single feeding of colostrum, but
      not milk replacer, was sufficient to support cervical cell proliferation at 12 h
      postnatal. IGF1 supplementation induced cell proliferation in replacer-fed gilts,
      and increased cervical pAKT and BCL2 levels in colostrum-fed gilts and replacer
      fed gilts at 12 h postnatal. Results indicate that age and nursing support
      porcine cervical development, support is initiated at first ingestion of
      colostrum, IGF1 may be lactocrine-active, and identification of lactocrine-active
      factors can be accomplished by 12 h postnatal using this bioassay system. 

PMID- 25074920
TI  - p53Psi is a transcriptionally inactive p53 isoform able to reprogram cells toward
      a metastatic-like state.
AB  - Although much is known about the underlying mechanisms of p53 activity and
      regulation, the factors that influence the diversity and duration of p53
      responses are not well understood. Here we describe a unique mode of p53
      regulation involving alternative splicing of the TP53 gene. We found that the use
      of an alternative 3' splice site in intron 6 generates a unique p53 isoform,
      dubbed p53Psi. At the molecular level, p53Psi is unable to bind to DNA and does
      not transactivate canonical p53 target genes. However, like certain p53 gain-of
      function mutants, p53Psi attenuates the expression of E-cadherin, induces
      expression of markers of the epithelial-mesenchymal transition, and enhances the
      motility and invasive capacity of cells through a unique mechanism involving the
      regulation of cyclophilin D activity, a component of the mitochondrial inner pore
      permeability. Hence, we propose that p53Psi encodes a separation-of-function
      isoform that, although lacking canonical p53 tumor suppressor/transcriptional
      activities, is able to induce a prometastatic program in a transcriptionally
      independent manner. 

PMID- 25074921
TI  - How blebs and pseudopods cooperate during chemotaxis.
AB  - Two motors can drive extension of the leading edge of motile cells: actin
      polymerization and myosin-driven contraction of the cortex, producing fluid
      pressure and the formation of blebs. Dictyostelium cells can move with both blebs
      and actin-driven pseudopods at the same time, and blebs, like pseudopods, can be
      orientated by chemotactic gradients. Here we ask how bleb sites are selected and
      how the two forms of projection cooperate. We show that membrane curvature is an
      important, yet overlooked, factor. Dictyostelium cells were observed moving under
      agarose, which efficiently induces blebbing, and the dynamics of membrane
      deformations were analyzed. Blebs preferentially originate from negatively curved
      regions, generated on the flanks of either extending pseudopods or blebs
      themselves. This is true of cells at different developmental stages, chemotaxing
      to either folate or cyclic AMP and moving with both blebs and pseudopods or with
      blebs only. A physical model of blebbing suggests that detachment of the cell
      membrane is facilitated in concave areas of the cell, where membrane tension
      produces an outward directed force, as opposed to pulling inward in convex
      regions. Our findings assign a role to membrane tension in spatially coupling
      blebs and pseudopods, thus contributing to clustering protrusions to the cell
      front. 

PMID- 25074923
TI  - Activation of the double-stranded RNA-dependent protein kinase PKR by small
      ubiquitin-like modifier (SUMO).
AB  - The dsRNA-dependent kinase PKR is an interferon-inducible protein with ability to
      phosphorylate the alpha subunit of the eukaryotic initiation factor (eIF)-2
      complex, resulting in a shut-off of general translation, induction of apoptosis,
      and inhibition of virus replication. Here we analyzed the modification of PKR by
      the small ubiquitin-like modifiers SUMO1 and SUMO2 and evaluated the consequences
      of PKR SUMOylation. Our results indicate that PKR is modified by both SUMO1 and
      SUMO2, in vitro and in vivo. We identified lysine residues Lys-60, Lys-150, and
      Lys-440 as SUMOylation sites in PKR. We show that SUMO is required for efficient
      PKR-dsRNA binding, PKR dimerization, and eIF2alpha phosphorylation. Furthermore,
      we demonstrate that SUMO potentiates the inhibition of protein synthesis induced
      by PKR in response to dsRNA, whereas a PKR SUMOylation mutant is impaired in its
      ability to inhibit protein synthesis and shows reduced capability to control
      vesicular stomatitis virus replication and to induce apoptosis in response to
      vesicular stomatitis virus infection. In summary, our data demonstrate the
      important role of SUMO in processes mediated by the activation of PKR. 

PMID- 25074924
TI  - Expression of the clustered NeuAcalpha2-3Galbeta O-glycan determines the cell
      differentiation state of the cells.
AB  - Human embryonic stem cells (hESCs) are pluripotent stem cells from early embryos,
      and their self-renewal capacity depends on the sustained expression of hESC
      specific molecules and the suppressed expression of differentiation-associated
      genes. To discover novel molecules expressed on hESCs, we generated a panel of
      monoclonal antibodies against undifferentiated hESCs and evaluated their ability
      to mark cancer cells, as well as hESCs. MAb7 recognized undifferentiated hESCs
      and showed a diffuse band with molecular mass of >239 kDa in the lysates of
      hESCs. Although some amniotic epithelial cells expressed MAb7 antigen, its
      expression was barely detected in normal human keratinocytes, fibroblasts, or
      endothelial cells. The expression of MAb7 antigen was observed only in pancreatic
      and gastric cancer cells, and its levels were elevated in metastatic and poorly
      differentiated cancer cell lines. Analyses of MAb7 antigen suggested that the
      clustered NeuAcalpha2-3Galbeta O-linked oligosaccharides on DMBT1 (deleted in
      malignant brain tumors 1) were critical for MAb7 binding in cancer cells.
      Although features of MAb7 epitope were similar with those of TRA-1-60,
      distribution of MAb7 antigen in cancer cells was different from that of TRA-1-60
      antigen. Exposure of a histone deacetylase inhibitor to differentiated gastric
      cancer MKN74 cells evoked the expression of MAb7 antigen, whereas DMBT1
      expression remained unchanged. Cell sorting followed by DNA microarray analyses
      identified the down-regulated genes responsible for the biosynthesis of MAb7
      antigen in MKN74 cells. In addition, treatment of metastatic pancreatic cancer
      cells with MAb7 significantly abrogated the adhesion to endothelial cells. These
      results raised the possibility that MAb7 epitope is a novel marker for
      undifferentiated cells such as hESCs and cancer stem-like cells and plays a
      possible role in the undifferentiated cells. 

PMID- 25074925
TI  - Pharmacological profile of brain-derived neurotrophic factor (BDNF) splice
      variant translation using a novel drug screening assay: a "quantitative code".
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) is a key regulator of
      neuronal development and plasticity. BDNF is a major pharmaceutical target in
      neurodevelopmental and psychiatric disorders. However, pharmacological modulation
      of this neurotrophin is challenging because BDNF is generated by multiple,
      alternatively spliced transcripts with different 5'- and 3'UTRs. Each BDNF mRNA
      variant is transcribed independently, but translation regulation is unknown. To
      evaluate the translatability of BDNF transcripts, we developed an in vitro
      luciferase assay in human neuroblastoma cells. In unstimulated cells, each BDNF
      5'- and 3'UTR determined a different basal translation level of the luciferase
      reporter gene. However, constructs with either a 5'UTR or a 3'UTR alone showed
      poor translation modulation by BDNF, KCl, dihydroxyphenylglycine, AMPA, NMDA,
      dopamine, acetylcholine, norepinephrine, or serotonin. Constructs consisting of
      the luciferase reporter gene flanked by the 5'UTR of one of the most abundant
      BDNF transcripts in the brain (exons 1, 2c, 4, and 6) and the long 3'UTR
      responded selectively to stimulation with the different receptor agonists, and
      only transcripts 2c and 6 were increased by the antidepressants desipramine and
      mirtazapine. We propose that BDNF mRNA variants represent "a quantitative code"
      for regulated expression of the protein. Thus, to discriminate the efficacy of
      drugs in stimulating BDNF synthesis, it is appropriate to use variant-specific in
      vitro screening tests. 

PMID- 25074926
TI  - Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and
      complex regulation of ligand-induced activation.
AB  - TYRO3, AXL, and MER receptors (TAMs) are three homologous type I receptor
      tyrosine kinases that are activated by endogenous ligands, protein S (PROS1) and
      growth arrest-specific gene 6 (GAS6). These ligands can either activate TAMs as
      soluble factors, or, in turn, opsonize phosphatidylserine (PS) on apoptotic cells
      (ACs) and serve as bridging molecules between ACs and TAMs. Abnormal expression
      and activation of TAMs have been implicated in promoting proliferation and
      survival of cancer cells, as well as in suppressing anti-tumor immunity. Despite
      the fact that TAM receptors share significant similarity, little is known about
      the specificity of interaction between TAM receptors and their ligands,
      particularly in the context of ACs, and about the functional diversity of TAM
      receptors. To study ligand-mediated activation of TAMs, we generated a series of
      reporter cell lines expressing chimeric TAM receptors. Using this system, we
      found that each TAM receptor has a unique pattern of interaction with and
      activation by GAS6 and PROS1, which is also differentially affected by the
      presence of ACs, PS-containing lipid vesicles and enveloped virus. We also
      demonstrated that gamma-carboxylation of ligands is essential for the full
      activation of TAMs and that soluble immunoglobulin-like TAM domains act as
      specific ligand antagonists. These studies demonstrate that, despite their
      similarity, TYRO3, AXL, and MER are likely to perform distinct functions in both
      immunoregulation and the recognition and removal of ACs. 

PMID- 25074927
TI  - Coronavirus Nsp10, a critical co-factor for activation of multiple replicative
      enzymes.
AB  - The RNA-synthesizing machinery of the severe acute respiratory syndrome
      Coronavirus (SARS-CoV) is composed of 16 non-structural proteins (nsp1-16)
      encoded by ORF1a/1b. The 148-amino acid nsp10 subunit contains two zinc fingers
      and is known to interact with both nsp14 and nsp16, stimulating their respective
      3'-5' exoribonuclease and 2'-O-methyltransferase activities. Using alanine
      scanning mutagenesis, in cellulo bioluminescence resonance energy transfer
      experiments, and in vitro pulldown assays, we have now identified the key
      residues on the nsp10 surface that interact with nsp14. The functional
      consequences of mutations introduced at these positions were first evaluated
      biochemically by monitoring nsp14 exoribonuclease activity. Disruption of the
      nsp10-nsp14 interaction abrogated the nsp10-driven activation of the nsp14
      exoribonuclease. We further showed that the nsp10 surface interacting with nsp14
      overlaps with the surface involved in the nsp10-mediated activation of nsp16 2'-O
      methyltransferase activity, suggesting that nsp10 is a major regulator of SARS
      CoV replicase function. In line with this notion, reverse genetics experiments
      supported an essential role of the nsp10 surface that interacts with nsp14 in
      SARS-CoV replication, as several mutations that abolished the interaction in
      vitro yielded a replication-negative viral phenotype. In contrast, mutants in
      which the nsp10-nsp16 interaction was disturbed proved to be crippled but viable.
      These experiments imply that the nsp10 surface that interacts with nsp14 and
      nsp16 and possibly other subunits of the viral replication complex may be a
      target for the development of antiviral compounds against pathogenic
      coronaviruses. 

PMID- 25074928
TI  - Chronic ethanol consumption inhibits glucokinase transcriptional activity by Atf3
      and triggers metabolic syndrome in vivo.
AB  - Chronic ethanol consumption induces pancreatic beta-cell dysfunction through
      glucokinase (Gck) nitration and down-regulation, leading to impaired glucose
      tolerance and insulin resistance, but the underlying mechanism remains largely
      unknown. Here, we demonstrate that Gck gene expression and promoter activity in
      pancreatic beta-cells were suppressed by chronic ethanol exposure in vivo and in
      vitro, whereas expression of activating transcription factor 3 (Atf3) and its
      binding to the putative Atf/Creb site (from -287 to -158 bp) on the Gck promoter
      were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the
      positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment
      of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the
      interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3
      siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and
      beta-cell dysfunction, followed by the amelioration of impaired glucose tolerance
      and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters
      beta-cell dysfunction via Gck down-regulation and that its loss ameliorates
      metabolic syndrome and could be a potential therapeutic target in treating type 2
      diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and
      alcohol consumption-induced metabolic impairment and thus may be the major
      negative regulator for glucose homeostasis. 

PMID- 25074929
TI  - The collagen-like protein gp12 is a temperature-dependent reversible binder of
      SPP1 viral capsids.
AB  - Icosahedral capsids of viruses are lattices of defined geometry and homogeneous
      size. The (quasi-)equivalent organization of their protein building blocks
      provides, in numerous systems, the binding sites to assemble arrays of viral
      polypeptides organized with nanometer precision that protrude from the capsid
      surface. The capsid of bacterial virus (bacteriophage) SPP1 exposes, at its
      surface, the 6.6-kDa viral polypeptide gp12 that binds to the center of hexamers
      of the major capsid protein. Gp12 forms an elongated trimer with collagen-like
      properties. This is consistent with the fold of eight internal GXY repeats of
      gp12 to build a stable intersubunit triple helix in a prokaryotic setting. The
      trimer dissociates and unfolds at near physiological temperatures, as reported
      for eukaryotic collagen. Its structural organization is reacquired within seconds
      upon cooling. Interaction with the SPP1 capsid hexamers strongly stabilizes gp12,
      increasing its Tm to 54  degrees C. Above this temperature, gp12 dissociates from
      its binding sites and unfolds reversibly. Multivalent binding of gp12 trimers to
      the capsid is highly cooperative. The capsid lattice also provides a platform to
      assist folding and association of unfolded gp12 polypeptides. The original
      physicochemical properties of gp12 offer a thermoswitchable system for
      multivalent binding of the polypeptide to the SPP1 capsid surface. 

PMID- 25074930
TI  - The merozoite surface protein 1 complex is a platform for binding to human
      erythrocytes by Plasmodium falciparum.
AB  - Plasmodium falciparum is the causative agent of the most severe form of malaria
      in humans. The merozoite, an extracellular stage of the parasite lifecycle,
      invades erythrocytes in which they develop. The most abundant protein on the
      surface of merozoites is merozoite surface protein 1 (MSP1), which consists of
      four processed fragments. Studies indicate that MSP1 interacts with other
      peripheral merozoite surface proteins to form a large complex. Successful
      invasion of merozoites into host erythrocytes is dependent on this protein
      complex; however, the identity of all components and its function remain largely
      unknown. We have shown that the peripheral merozoite surface proteins MSPDBL1 and
      MSPDBL2 are part of the large MSP1 complex. Using surface plasmon resonance, we
      determined the binding affinities of MSPDBL1 and MSPDBL2 to MSP1 to be in the
      range of 2-4 * 10(-7) m. Both proteins bound to three of the four proteolytically
      cleaved fragments of MSP1 (p42, p38, and p83). In addition, MSPDBL1 and MSPDBL2,
      but not MSP1, bound directly to human erythrocytes. This demonstrates that the
      MSP1 complex acts as a platform for display of MSPDBL1 and MSPDBL2 on the
      merozoite surface for binding to receptors on the erythrocyte and invasion. 

PMID- 25074931
TI  - Molecular mechanisms of cellular cholesterol efflux.
AB  - Most types of cells in the body do not express the capability of catabolizing
      cholesterol, so cholesterol efflux is essential for homeostasis. For instance,
      macrophages possess four pathways for exporting free (unesterified) cholesterol
      to extracellular high density lipoprotein (HDL). The passive processes include
      simple diffusion via the aqueous phase and facilitated diffusion mediated by
      scavenger receptor class B, type 1 (SR-BI). Active pathways are mediated by the
      ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, which are membrane lipid
      translocases. The efflux of cellular phospholipid and free cholesterol to
      apolipoprotein A-I promoted by ABCA1 is essential for HDL biogenesis. Current
      understanding of the molecular mechanisms involved in these four efflux pathways
      is presented in this minireview. 

PMID- 25074932
TI  - Structure and mechanism of the phycobiliprotein lyase CpcT.
AB  - Pigmentation of light-harvesting phycobiliproteins of cyanobacteria requires
      covalent attachment of open-chain tetrapyrroles, bilins, to the apoproteins.
      Thioether formation via addition of a cysteine residue to the 3-ethylidene
      substituent of bilins is mediated by lyases. T-type lyases are responsible for
      attachment to Cys-155 of phycobiliprotein beta-subunits. We present crystal
      structures of CpcT (All5339) from Nostoc (Anabaena) sp. PCC 7120 and its complex
      with phycocyanobilin at 1.95 and 2.50 A resolution, respectively. CpcT forms a
      dimer and adopts a calyx-shaped beta-barrel fold. Although the overall structure
      of CpcT is largely retained upon chromophore binding, arginine residues at the
      opening of the binding pocket undergo major rotameric rearrangements anchoring
      the propionate groups of phycocyanobilin. Based on the structure and mutational
      analysis, a reaction mechanism is proposed that accounts for chromophore
      stabilization and regio- and stereospecificity of the addition reaction. At the
      dimer interface, a loop extending from one subunit partially shields the opening
      of the phycocyanobilin binding pocket in the other subunit. Deletion of the loop
      or disruptions of the dimer interface significantly reduce CpcT lyase activity,
      suggesting functional relevance of the dimer. Dimerization is further enhanced by
      chromophore binding. The chromophore is largely buried in the dimer, but in the
      monomer, the 3-ethylidene group is accessible for the apophycobiliprotein,
      preferentially from the chromophore alpha-side. Asp-163 and Tyr-65 at the beta-
      and alpha-face near the E-configured ethylidene group, respectively, support the
      acid-catalyzed nucleophilic Michael addition of cysteine 155 of the apoprotein to
      an N-acylimmonium intermediate proposed by Grubmayr and Wagner (Grubmayr, K., and
      Wagner, U. G. (1988) Monatsh. Chem. 119, 965-983). 

PMID- 25074933
TI  - Dimeric switch of Hakai-truncated monomers during substrate recognition: insights
      from solution studies and NMR structure.
AB  - Hakai, an E3 ubiquitin ligase, disrupts cell-cell contacts in epithelial cells
      and is up-regulated in human colon and gastric adenocarcinomas. Hakai acts
      through its phosphotyrosine-binding (HYB) domain, which bears a dimeric fold that
      recognizes the phosphotyrosine motifs of E-cadherin, cortactin, DOK1, and other
      Src substrates. Unlike the monomeric nature of the SH2 and phosphotyrosine
      binding domains, the architecture of the HYB domain consists of an atypical, zinc
      coordinated tight homodimer. Here, we report a C-terminal truncation mutant of
      the HYB domain (HYB(DeltaC)), comprising amino acids 106-194, which exists as a
      monomer in solution. The NMR structure revealed that this deletion mutant
      undergoes a dramatic structural change caused by a rearrangement of the atypical
      zinc-coordinated unit in the C terminus of the HYB domain to a C2H2-like zinc
      finger in HYB(DeltaC). Moreover, using isothermal titration calorimetry, we show
      that dimerization of HYB(DeltaC) can be induced using a phosphotyrosine substrate
      peptide. This ligand-induced dimerization of HYB(DeltaC) is further validated
      using analytical ultracentrifugation, size-exclusion chromatography, NMR
      relaxation studies, dynamic light scattering, and circular dichroism experiments.
      Overall, these observations suggest that the dimeric architecture of the HYB
      domain is essential for the phosphotyrosine-binding property of Hakai. 

PMID- 25074934
TI  - Cell surface epidermal growth factor receptors increase Src and c-Cbl activity
      and receptor ubiquitylation.
AB  - There is an established role for the endocytic pathway in regulation of epidermal
      growth factor receptor (EGFR) signaling to downstream effectors. However, because
      ligand-mediated EGFR endocytosis utilizes multiple "moving parts," dissecting the
      spatial versus temporal contributions has been challenging. Blocking all
      endocytic trafficking can have unintended effects on other receptors as well as
      give rise to compensatory mechanisms, both of which impact interpretation of EGFR
      signaling. To overcome these limitations, we used epidermal growth factor (EGF)
      conjugated to polystyrene beads (EGF beads). EGF beads simultaneously activate
      the EGFR while blocking its endocytosis and allow analysis of EGFR signaling from
      the plasma membrane. Human telomerase immortalized corneal epithelial (hTCEpi)
      cells were used to model normal epithelial cell biology. In hTCEpi cells, both
      cell surface and intracellular EGFRs exhibited dose-dependent increases in
      effector activity after 15 min of ligand stimulation, but only the serine
      phosphorylation of signal transducer and activator of transcription 3 (STAT3) was
      statistically significant when accounting for receptor phosphorylation. However,
      over time with physiological levels of receptor phosphorylation, cell surface
      receptors produced either enhanced or sustained mitogen-activated protein kinase
      kinase (MEK), Casitas B-lineage lymphoma (c-Cbl), and the pro-oncogene Src
      activity. These increases in effector communication by cell surface receptors
      resulted in an increase in EGFR ubiquitylation with sustained ligand incubation.
      Together, these data indicate that spatial regulation of EGFR signaling may be an
      important regulatory mechanism in receptor down-regulation. 

PMID- 25074935
TI  - Multiple interactions between cytoplasmic domains regulate slow deactivation of
      Kv11.1 channels.
AB  - The intracellular domains of many ion channels are important for fine-tuning
      their gating kinetics. In Kv11.1 channels, the slow kinetics of channel
      deactivation, which are critical for their function in the heart, are largely
      regulated by the N-terminal N-Cap and Per-Arnt-Sim (PAS) domains, as well as the
      C-terminal cyclic nucleotide-binding homology (cNBH) domain. Here, we use mutant
      cycle analysis to probe for functional interactions between the N-Cap/PAS domains
      and the cNBH domain. We identified a specific and stable charge-charge
      interaction between Arg(56) of the PAS domain and Asp(803) of the cNBH domain, as
      well an additional interaction between the cNBH domain and the N-Cap, both of
      which are critical for maintaining slow deactivation kinetics. Furthermore, we
      found that positively charged arginine residues within the disordered region of
      the N-Cap interact with negatively charged residues of the C-linker domain.
      Although this interaction is likely more transient than the PAS-cNBD interaction,
      it is strong enough to stabilize the open conformation of the channel and thus
      slow deactivation. These findings provide novel insights into the slow
      deactivation mechanism of Kv11.1 channels. 

PMID- 25074936
TI  - Assignment of 2'-O-methyltransferases to modification sites on the mammalian
      mitochondrial large subunit 16 S ribosomal RNA (rRNA).
AB  - Advances in proteomics and large scale studies of potential mitochondrial
      proteins have led to the identification of many novel mitochondrial proteins in
      need of further characterization. Among these novel proteins are three mammalian
      rRNA methyltransferase family members RNMTL1, MRM1, and MRM2. MRM1 and MRM2 have
      bacterial and yeast homologs, whereas RNMTL1 appears to have evolved later in
      higher eukaryotes. We recently confirmed the localization of the three proteins
      to mitochondria, specifically in the vicinity of mtDNA nucleoids. In this study,
      we took advantage of the ability of 2'-O-ribose modification to block site
      specific cleavage of RNA by DNAzymes to show that MRM1, MRM2, and RNMTL1 are
      responsible for modification of human large subunit rRNA at residues G(1145),
      U(1369), and G(1370), respectively. 

PMID- 25074937
TI  - Plasticity-related gene 5 promotes spine formation in murine hippocampal neurons.
AB  - The transmembrane protein plasticity-related genes 3 and 5 (PRG3 and PRG5)
      increase filopodial formation in various cell lines, independently of Cdc42.
      However, information on the effects of PRG5 during neuronal development is
      sparse. Here, we present several lines of evidence for the involvement of PRG5 in
      the genesis and stabilization of dendritic spines. First, PRG5 was strongly
      expressed during mouse brain development from embryonic day 14 (E14), peaked
      around the time of birth, and remained stable at least until early adult stages
      (i.e. P30). Second, on a subcellular level, PRG5 expression shifted from an equal
      distribution along all neurites toward accumulation only along dendrites during
      hippocampal development in vitro. Third, overexpression of PRG5 in immature
      hippocampal neurons induced formation of spine-like structures ahead of time.
      Proper amino acid sequences in the extracellular domains (D1 to D3) of PRG5 were
      a prerequisite for trafficking and induction of spine-like structures, as shown
      by mutation analysis. Fourth, at stages when spines are present, knockdown of
      PRG5 reduced the number but not the length of protrusions. This was accompanied
      by a decrease in the number of excitatory synapses and, consequently, by a
      reduction of miniature excitatory postsynaptic current frequencies, although
      miniature excitatory postsynaptic current amplitudes remained similar. In turn,
      overexpressing PRG5 in mature neurons not only increased Homer-positive spine
      numbers but also augmented spine head diameters. Mechanistically, PRG5 interacts
      with phosphorylated phosphatidylinositols, phospholipids involved in dendritic
      spine formation by different lipid-protein assays. Taken together, our data
      propose that PRG5 promotes spine formation. 

PMID- 25074938
TI  - Phospholamban C-terminal residues are critical determinants of the structure and
      function of the calcium ATPase regulatory complex.
AB  - To determine the structural and regulatory role of the C-terminal residues of
      phospholamban (PLB) in the membranes of living cells, we fused fluorescent
      protein tags to PLB and sarco/endoplasmic reticulum calcium ATPase (SERCA).
      Alanine substitution of PLB C-terminal residues significantly altered
      fluorescence resonance energy transfer (FRET) from PLB to PLB and SERCA to PLB,
      suggesting a change in quaternary conformation of PLB pentamer and SERCA-PLB
      regulatory complex. Val to Ala substitution at position 49 (V49A) had
      particularly large effects on PLB pentamer structure and PLB-SERCA regulatory
      complex conformation, increasing and decreasing probe separation distance,
      respectively. We also quantified a decrease in oligomerization affinity, an
      increase in binding affinity of V49A-PLB for SERCA, and a gain of inhibitory
      function as quantified by calcium-dependent ATPase activity. Notably, deletion of
      only a few C-terminal residues resulted in significant loss of PLB membrane
      anchoring and mislocalization to the cytoplasm and nucleus. C-terminal
      truncations also resulted in progressive loss of PLB-PLB FRET due to a decrease
      in the apparent affinity of PLB oligomerization. We quantified a similar decrease
      in the binding affinity of truncated PLB for SERCA and loss of inhibitory
      potency. However, despite decreased SERCA-PLB binding, intermolecular FRET for
      Val(49)-stop (V49X) truncation mutant was paradoxically increased as a result of
      an 11.3-A decrease in the distance between donor and acceptor fluorophores. We
      conclude that PLB C-terminal residues are critical for localization,
      oligomerization, and regulatory function. In particular, the PLB C terminus is an
      important determinant of the quaternary structure of the SERCA regulatory
      complex. 

PMID- 25074939
TI  - Overexpression of MERTK receptor tyrosine kinase in epithelial cancer cells
      drives efferocytosis in a gain-of-function capacity.
AB  - MERTK, a member of the TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases, has
      complex and diverse roles in cell biology. On the one hand, knock-out of MERTK
      results in age-dependent autoimmunity characterized by failure of apoptotic cell
      clearance, while on the other, MERTK overexpression in cancer drives classical
      oncogene pathways leading to cell transformation. To better understand the
      interplay between cell transformation and efferocytosis, we stably expressed
      MERTK in human MCF10A cells, a non-tumorigenic breast epithelial cell line devoid
      of endogenous MERTK. While stable expression of MERTK in MCF10A resulted in
      enhanced motility and AKT-mediated chemoprotection, MERTK-10A cells did not form
      stable colonies in soft agar, or enhance proliferation compared with parental
      MCF10A cells. Concomitant to chemoresistance, MERTK also stimulated efferocytosis
      in a gain-of-function capacity. However, unlike AXL, MERTK activation was highly
      dependent on apoptotic cells, suggesting MERTK may preferentially interface with
      phosphatidylserine. Consistent with this idea, knockdown of MERTK in breast
      cancer cells MDA-MB 231 reduced efferocytosis, while transient or stable
      expression of MERTK stimulated apoptotic cell clearance in all cell lines tested.
      Moreover, human breast cancer cells with higher endogenous MERTK showed higher
      levels of efferocytosis that could be blocked by soluble TAM receptors. Finally,
      through MERTK, apoptotic cells induced PD-L1 expression, an immune checkpoint
      blockade, suggesting that cancer cells may adopt MERTK-driven efferocytosis as an
      immune suppression mechanism for their advantage. These data collectively
      identify MERTK as a significant link between cancer progression and
      efferocytosis, and a potentially unrealized tumor-promoting event when MERTK is
      overexpressed in epithelial cells. 

PMID- 25074941
TI  - Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating
      lysosomal acid sphingomyelinase.
AB  - The inducible expression of heat shock protein 70.1 (Hsp70.1) plays
      cytoprotective roles in its molecular chaperone function. Binding of Hsp70 to an
      endolysosomal phospholipid, bis(monoacylglycero)phosphate (BMP), has been
      recently shown to stabilize lysosomal membranes by enhancing acid
      sphingomyelinase (ASM) activity in cancer cells. Using the monkey experimental
      paradigm, we have reported that calpain-mediated cleavage of oxidized Hsp70.1
      causes neurodegeneration in the hippocampal cornu ammonis 1 (CA1), whereas
      expression of Hsp70.1 in the motor cortex without calpain activation contributes
      to neuroprotection. However, the molecular mechanisms of the lysosomal
      destabilization/stabilization determining neuronal cell fate have not been
      elucidated. To elucidate whether regulation of lysosomal ASM could affect the
      neuronal fate, we analyzed Hsp70.1-BMP binding and ASM activity by comparing the
      motor cortex and the CA1. We show that Hsp70.1 being localized at the lysosomal
      membrane, lysosomal lipid BMP levels, and the lipid binding domain of Hsp70.1 are
      crucial for Hsp70.1-BMP binding. In the postischemic motor cortex, Hsp70.1 being
      localized at the lysosomal membrane could bind to BMP without calpain activation
      and decreased BMP levels, resulting in increasing ASM activity and lysosomal
      stability. However, in the postischemic CA1, calpain activation and a concomitant
      decrease in the lysosomal membrane localization of Hsp70.1 and BMP levels may
      diminish Hsp70.1-BMP binding, resulting in decreased ASM activity and lysosomal
      rupture with leakage of cathepsin B into the cytosol. A TUNEL assay revealed the
      differential neuronal vulnerability between the CA1 and the motor cortex. These
      results suggest that regulation of ASM activation in vivo by Hsp70.1-BMP affects
      lysosomal stability and neuronal survival or death after ischemia/reperfusion. 

PMID- 25074940
TI  - N-terminal domain of prion protein directs its oligomeric association.
AB  - The self-association of prion protein (PrP) is a critical step in the pathology
      of prion diseases. It is increasingly recognized that small non-fibrillar beta
      sheet-rich oligomers of PrP may be of crucial importance in the prion disease
      process. Here, we characterize the structure of a well defined beta-sheet-rich
      oligomer, containing ~12 PrP molecules, and often enclosing a central cavity,
      formed using full-length recombinant PrP. The N-terminal region of prion protein
      (residues 23-90) is required for the formation of this distinct oligomer; a
      truncated form comprising residues 91-231 forms a broad distribution of
      aggregated species. No infectivity or toxicity was found using cell and animal
      model systems. This study demonstrates that examination of the full repertoire of
      conformers and assembly states that can be accessed by PrP under specific
      experimental conditions should ideally be done using the full-length protein. 

PMID- 25074943
TI  - Inhaled corticosteroids do not influence the early inflammatory response and
      clinical presentation of hospitalized subjects with COPD exacerbation.
AB  - BACKGROUND: Inhaled corticosteroids are anti-inflammatory medications that can
      down-regulate the immunologic response in patients with COPD; however, their role
      at onset of COPD exacerbation is still not understood. The aim of this study was
      to assess the early inflammatory response and clinical presentation of patients
      with COPD exacerbation mediated by inhaled corticosteroids. METHODS: Prospective
      data were collected on 123 hospitalized subjects with COPD exacerbation over a 30
      month period at 2 Spanish university hospitals. Based on domiciliary use,
      comparative analyses were performed between subjects who did not use inhaled
      corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum
      biomarkers were recorded on admission to the hospital (day 1) and on day 3;
      clinical, physiological, microbiological, and severity data and
      mortality/readmission rates were also recorded. RESULTS: At days 1 and 3, both
      groups showed a similar inflammatory response; fluticasone produced lower levels
      of interleukin-8 compared with budesonide (P < .01). All clinical features
      considered were similar in the 2 groups; multivariate analysis predicting
      clinical complications on hospitalization showed air-flow obstruction severity as
      the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P = .02).
      CONCLUSIONS: Our study demonstrates a lack of inhaled corticosteroid influence in
      the early systemic inflammatory response to and clinical presentation of COPD
      exacerbation.

PMID- 25074945
TI  - Belinostat approved for use in treating rare lymphoma.

PMID- 25074942
TI  - Adropin is a brain membrane-bound protein regulating physical activity via the NB
      3/Notch signaling pathway in mice.
AB  - Adropin is a highly conserved polypeptide that has been suggested to act as an
      endocrine factor that plays important roles in metabolic regulation, insulin
      sensitivity, and endothelial functions. However, in this study, we provide
      evidence demonstrating that adropin is a plasma membrane protein expressed
      abundantly in the brain. Using a yeast two-hybrid screening approach, we
      identified NB-3/Contactin 6, a brain-specific, non-canonical, membrane-tethered
      Notch1 ligand, as an interaction partner of adropin. Furthermore, this
      interaction promotes NB3-induced activation of Notch signaling and the expression
      of Notch target genes. We also generated and characterized adropin knockout mice
      to explore the role of adropin in vivo. Adropin knockout mice exhibited decreased
      locomotor activity and impaired motor coordination coupled with defective synapse
      formation, a phenotype similar to NB-3 knockout mice. Taken together, our data
      suggest that adropin is a membrane-bound protein that interacts with the brain
      specific Notch1 ligand NB3. It regulates physical activity and motor coordination
      via the NB-3/Notch signaling pathway and plays an important role in cerebellum
      development in mice. 

PMID- 25074944
TI  - Home mechanical ventilation for COPD: high-intensity versus target volume
      noninvasive ventilation.
AB  - BACKGROUND: High-intensity noninvasive ventilation (HI-NIV) is the most effective
      means of improving several physiological and clinical parameters in subjects with
      chronic hypercapnic COPD. Whether the newer hybrid mode using target tidal volume
      noninvasive ventilation (target V(T) NIV) provides additional benefits remains
      unclear. METHODS: Subjects with COPD successfully established on long-term HI-NIV
      were switched to target V(T) NIV. Optimal target V(T) settings according to
      nocturnal transcutaneous P(CO2) measurements were achieved following a randomized
      crossover trial using 8 mL/kg ideal body weight and 110% of individual V(T)
      during HI-NIV, respectively. The following parameters were compared at the
      beginning of the trial while subjects were on HI-NIV, and after 3 months on
      optimal target V(T) NIV: sleep quality by polysomnography, overnight gas
      exchange, subjects' tolerance, overnight pneumotachygraphic measurements during
      NIV, health-related quality of life (severe respiratory insufficiency
      questionnaire), exercise capacity (6-min walk test), and lung function. RESULTS:
      Ten of 14 subjects completed the study. There were no differences between HI-NIV
      and target V(T) NIV in any of the above-mentioned parameters. Specifically, the
      mean overnight transcutaneous P(CO2) was equivalent under each form of
      ventilation (both 45 +/- 5 mm Hg, P = .75). CONCLUSIONS: Switching subjects from
      well-established HI-NIV to target V(T) NIV shows no clinical benefits in chronic
      hypercapnic COPD. In particular, sleep quality, the control of nocturnal
      hypoventilation, daytime hypercapnia, overnight ventilation patterns, subjects'
      tolerance, health-related quality of life, lung function, and exercise capability
      were all similar in subjects who underwent HI-NIV and target V(T) NIV.
      Nevertheless, target V(T) NIV might offer some physiological advantages in
      breathing pattern and might be beneficial in some individual patients. (German
      Clinical Trials Register [www.drks.de] Registration DRKS00000450.).

PMID- 25074946
TI  - Rhode Island's opioid epidemic response features collaborative practice model.

PMID- 25074947
TI  - Discussion continues on content, format of consumer drug leaflets.

PMID- 25074950
TI  - Pharmacy implications of the HIPAA Breach Notification Rule.

PMID- 25074949
TI  - Francke Medalist Colin R. Hitchings dies at 75.

PMID- 25074951
TI  - Portfolio preparation for residency candidates.

PMID- 25074952
TI  - Driving change in ambulatory care.

PMID- 25074953
TI  - Introduction to the proceedings of the summit.
AB  - Proceedings of the ASHP Ambulatory Care Summit. Conducted by the American Society
      of Health-System Pharmacists and the ASHP Research and Education Foundation,
      Dallas, Texas, March 3-4, 2014

PMID- 25074954
TI  - Defining and advancing ambulatory care pharmacy practice: it is time to lengthen
      our stride.
AB  - PURPOSE: This paper reviews the basic tenets of ambulatory care pharmacy
      practice, including (1) the historical development of patient-centered care
      provided by pharmacists, (2) the need for and value of comprehensive medication
      management, (3) the education, training, and qualifications of pharmacists, and
      (4) demonstrated improvement in health and healthcare outcomes from pharmacists'
      services. SUMMARY: When ambulatory care pharmacists engage in patient care to
      their full capacity, physician time is saved, access to care is improved, and
      clinical and economic outcomes are enhanced. There is a need for ambulatory care
      pharmacists to work toward optimizing safe medication use and optimizing
      medication therapy for patients with diabetes, asthma, cardiovascular disease,
      and renal disease. Other opportunities for the development of ambulatory care
      pharmacy services exist in preventive care, precision therapeutics, medication
      therapy management, mitigation of healthcare disparities, and implementation of
      national healthcare reform. Interprofessional patient care teams should include
      ambulatory care pharmacists in patient-centered medical homes and accountable
      care organizations. Ambulatory care pharmacy practice would benefit by enhancing
      specialty residency training and by creating a residency/fellowship for advanced
      subspecialty clinical practice and research. Provider status is essential to
      recognize pharmacists as an integral part of the patient care team. CONCLUSION:
      By assertively advancing ambulatory care practice, pharmacy will help achieve the
      national priorities of improving patient care, patient health, and affordability
      of care.

PMID- 25074955
TI  - Patient care delivery and integration: stimulating advancement of ambulatory care
      pharmacy practice in an era of healthcare reform.
AB  - PURPOSE: This article discusses how to plan and implement an ambulatory care
      pharmacist service, how to integrate a hospital- or health-system-based service
      with the mission and operations of the institution, and how to help the
      institution meet its challenges related to quality improvement, continuity of
      care, and financial sustainability. SUMMARY: The steps in implementing an
      ambulatory care pharmacist service include (1) conducting a needs assessment, (2)
      aligning plans for the service with the mission and goals of the parent
      institution, (3) collaborating with patients and physicians, (4) standardizing
      the patient care process, (5) proposing the service, (6) attaining the necessary
      resources, (7) identifying stakeholders, (8) identifying applicable quality
      standards, (9) defining competency standards, (10) planning for service payment,
      and (11) monitoring outcomes. Ambulatory care pharmacists have current
      opportunities to become engaged with patient-centered medical homes, accountable
      care organizations, preventive and wellness programs, and continuity of care
      initiatives. Common barriers to the advancement of ambulatory care pharmacist
      services include lack of complete access to patient information, inadequate
      information technology, and lack of payment. CONCLUSION: Ambulatory care pharmacy
      practitioners must assertively promote appropriate medication use, provide
      patient-centered care, pursue integration with the patient care team, and seek
      appropriate recognition and compensation for the services they provide.

PMID- 25074956
TI  - Sustainable business models: systematic approach toward successful ambulatory
      care pharmacy practice.
AB  - PURPOSE: This article discusses considerations for making ambulatory care
      pharmacist services at least cost neutral and, ideally, generate a margin that
      allows for service expansion. SUMMARY: The four pillars of business
      sustainability are leadership, staffing, information technology, and
      compensation. A key facet of leadership in ambulatory care pharmacy practice is
      creating and expressing a clear vision for pharmacists' services. Staffing
      considerations include establishing training needs, maximizing efficiencies, and
      minimizing costs. Information technology is essential for efficiency in patient
      care delivery and outcomes assessment. The three domains of compensation are cost
      savings, pay for performance, and revenue generation. The following eight steps
      for designing and implementing an ambulatory care pharmacist service are
      discussed: (1) prepare a needs assessment, (2) analyze existing strengths,
      weaknesses, opportunities, and threats, (3) analyze service gaps and feasibility,
      (4) consider financial opportunities, (5) consider stakeholders' interests, (6)
      develop a business plan, (7) implement the service, and (8) measure outcomes.
      Potential future changes in national healthcare policy (such as pharmacist
      provider status and expanded pay for performance) could enhance the opportunities
      for sustainable ambulatory care pharmacy practice. CONCLUSION: The key challenges
      facing ambulatory care pharmacists are developing sustainable business models,
      determining which services yield a positive return on investment, and demanding
      payment for value-added services.

PMID- 25074957
TI  - Outcomes evaluation: striving for excellence in ambulatory care pharmacy
      practice.
AB  - PURPOSE: Key issues in measuring and improving the quality of healthcare are
      discussed with an emphasis on applying quality-improvement principles in
      ambulatory care pharmacy practice. SUMMARY: The various perspectives on
      healthcare quality (including those of patients, providers, and payers) are
      reviewed, and the basic principles of quality measurement and improvement are
      outlined. Many healthcare practitioners believe that the most effective way to
      improve healthcare is through balanced consideration of the structure, process,
      and outcomes of healthcare services. Overall progress in improving the quality of
      healthcare has been slow, in part because of lack of patient engagement, use of
      improvement methods that have not been fully tested, and inadequate attention to
      the systems of providing care. Ongoing efforts of national quality-improvement
      organizations are reviewed, including those of the government, accreditation
      bodies, payers, and professional associations. Of special interest in pharmacy is
      the work of the Pharmacy Quality Alliance, the Patient Safety and Clinical
      Pharmacy Services Collaborative, and the Center for Pharmacy Practice
      Accreditation. Ambulatory care pharmacists have important opportunities to
      improve healthcare quality, including by reducing adverse drug events, improving
      medication reconciliation and transitions of care, fostering medication
      adherence, improving patient medication self-management, providing immunization
      services, and reducing disparities in access to medications. CONCLUSION: To be
      fully effective, the national priority of improving the quality of healthcare
      must penetrate the work of individual healthcare practitioners, including
      ambulatory care pharmacists.

PMID- 25074959
TI  - How the summit's recommendations were developed.

PMID- 25074960
TI  - Recommendations of the summit.

PMID- 25074961
TI  - Building on the work of the summit.

PMID- 25074962
TI  - Making the vision and recommendations of the summit a reality.

PMID- 25074963
TI  - Harvey A.K. Whitney Lecture. The visible ingredient.

PMID- 25074964
TI  - Inaugural address of the Incoming President: The constant in the patient care
      equation.

PMID- 25074965
TI  - 2014 Report of the President and Chair of the Board. ASHP: aiming higher.

PMID- 25074966
TI  - 2014 Report of the Chief Executive Officer. ASHP is constructively dissatisfied.

PMID- 25074967
TI  - 2014 Report of the ASHP Treasurer. A growing and forward-looking organization.

PMID- 25074971
TI  - Professional policies approved by the 2014 ASHP House of Delegates: Las Vegas, NV
      June 3, 2014.

PMID- 25074973
TI  - Developing a crush: acute implantable cardioverter-defibrillator lead insulation
      break in a patient with multiple leads.

PMID- 25074972
TI  - Low incidence of permanent complications during catheter ablation for atrial
      fibrillation using open-irrigated catheters: a multicentre registry.
AB  - AIMS: Despite catheter ablation (CA) has become an accepted treatment option for
      symptomatic, drug-resistant atrial fibrillation (AF), the safety of this
      procedure continues to be cause for concern. The aim of the present study was to
      assess the incidence of complications with permanent sequelae of CA for AF using
      open-irrigated catheters in a contemporary, unselected population of consecutive
      patients. METHODS AND RESULTS: From 1 January 2011 to 31 December 2011, data from
      2167 consecutive patients who underwent CA for AF using an open-irrigated
      catheter in 29 Italian centres were collected. All the complications occurring to
      the patient from admission to the 30th post-procedural day were recorded. No
      procedure-related death was observed. Complications occurred in 81 patients
      (3.7%): 46 patients (2.1%) suffered vascular access complications; 13 patients
      (0.6%) cardiac tamponade, successfully drained in all the cases; six patients
      (0.3%) arterial thromboembolism (four transient ischaemic attack and two
      ischaemic strokes); five (0.2%) patients conservatively treated pericardial
      effusion; three patients (0.1%) phrenic nerve paralysis; three patients (0.1%)
      pericarditis; three patients (0.1%) haemothorax, and two patients (0.1%) other
      isolated adverse events. At multivariate analysis, only female sex [odds ratio
      (OR) 2.5, confidence interval (CI): 1.5-3.7, P < 001] and the operator experience
      (OR 0.5, CI: 0.4-0.7, P < 001) related to the complications. Only five (0.2%)
      patients developed permanent sequelae from their complications. CONCLUSION:
      Catheter ablation for AF with the use of open-irrigated catheters is currently
      affected by a very low rate of complications leading to permanent sequelae.

PMID- 25074974
TI  - Standards for device implantation and follow-up: personnel, equipment, and
      facilities: results of the European Heart Rhythm Association Survey.
AB  - Cardiac device implantation is the most common of all invasive cardiac
      electrophysiological procedures. Over 250 000 devices are implanted each year in
      Europe. The purpose of this European Heart Rhythm Association (EHRA) survey was
      to assess the facilities, personnel, and protocols of members of the EHRA
      electrophysiology (EP) research network involved in device implantation. There
      were 68 responses to the questionnaire. The survey responses were mainly (84%)
      from medium- to high-volume device implanting centres, performing >200 implants
      per year, with over 50% performing >400 implants per year. Most consultants are
      male (85%), half of all centres had no female consultants, and only one in six
      had more than one female consultant. There is trend towards specialization in
      device implantation. The combination of device implantation and EP is still
      common (76% of all centres) but only 34% of centres have consultants performing
      device implantation and coronary intervention. Moreover, 23% of centres have all
      device implantation performed by consultants who do not perform any other types
      of procedure. Cardiac device implantation as a day case is the planned admission
      for routine elective device implantation in 30% of hospitals, 47% of hospitals
      have a single night stay, and 23% of hospitals have admission durations of two or
      more nights. Device implantation is available as a 24 h service, 365 days a year
      in 38% of hospitals. The commonest other model was as a daytime service on
      weekdays in 45% of hospitals. 

PMID- 25074976
TI  - The effectiveness of interventions during and after residence in women's
      shelters: a meta-analysis.
AB  - BACKGROUND: Due to intimate partner violence (IPV), a proportion of some women
      seek safety from their abuser in shelters. Little is known yet about whether the
      received shelter interventions, offered during and after women's stay, are
      effective. Therefore, a meta-analysis of studies was performed, testing the
      effectiveness of interventions administered to female IPV victims during and/or
      after their residence in shelters, in terms of mental health, re-abuse and social
      outcomes. METHODS: From January 1985 through July 2011, five databases were
      searched for English-language articles. Original research articles evaluating the
      effects of interventions provided to IPV victims during and after shelter
      residence were identified. Hedges' g effect sizes and 95% confidence intervals
      (CIs) were calculated and pooled if three or more studies including one outcome
      type were available. RESULTS: Ten original studies, including a total number of
      726 female IPV victims, were analysed. We found that shelter interventions were
      effective in improving mental health outcomes (g = -0.39; 95% CI: 0.24-0.54), in
      decreasing abuse (g = 0.32; 95% CI: 0.08-0.55) and in improving social outcomes
      (g = 0.71; 95% CI: 0.54-0.88) in shelter-based abused women. CONCLUSION: This
      analysis suggests that interventions provided during and after stay in a shelter
      are effective in improving mental health, abuse and social outcomes, but further
      research has to confirm this. Moreover, future studies should compare different
      type of interventions and should evaluate cost-effectiveness.

PMID- 25074977
TI  - Mental health problems in undocumented and documented migrants: a survey study.
AB  - BACKGROUND: Undocumented migrants (UM) frequently report mental health problems.
      It is unknown to what extent these migrants seek help for these problems in
      general practice and how these issues are explored, discussed, registered and
      treated by GPs. OBJECTIVE: To gain insight in the registration and treatment of
      mental health problems in general practice of UM compared to documented migrants
      (DM). METHODS: A survey study of general practice patient records of UM and DM in
      nine general practices in the Netherlands. Consultation rates, registration of
      mental health problems, prescription of psychotropic medication and referrals to
      mental health care institutions of UM and DM patients were compared. RESULTS: A
      total of 541 migrants were included (325 UM and 216 DM). UM consulted a GP
      significantly less than DM (3.1 versus 4.9 times per year). Only 20.6% of the UM
      had at least one mental health problem diagnosis registered compared to 44.0% of
      the DM. In both groups, ~10% mentioned at least one main mental health complaint
      during the consultation that was not coded in the record. No significant
      differences were found in the prescription of psychotropic medication between the
      two groups. UM were referred less to mental health care institutions but more
      often to psychiatrists than to psychologists. CONCLUSION: UM had less
      consultations with their GP, and in these consultations, less mental health
      problems were registered. UM were referred less to psychologists but more often
      to psychiatrists. GPs are advised to explore and register mental health problems
      more actively in UM.

PMID- 25074975
TI  - Sleep spindles are related to schizotypal personality traits and thalamic
      glutamine/glutamate in healthy subjects.
AB  - BACKGROUND: Schizophrenia is a severe mental disorder affecting approximately 1%
      of the worldwide population. Yet, schizophrenia-like experiences (schizotypy) are
      very common in the healthy population, indicating a continuum between normal
      mental functioning and the psychosis found in schizophrenic patients. A continuum
      between schizotypy and schizophrenia would be supported if they share the same
      neurobiological origin. Two such neurobiological markers of schizophrenia are:
      (1) a reduction of sleep spindles (12-15 Hz oscillations during nonrapid eye
      movement sleep), likely reflecting deficits in thalamo-cortical circuits and (2)
      increased glutamine and glutamate (Glx) levels in the thalamus. Thus, this study
      aimed to investigate whether sleep spindles and Glx levels are related to
      schizotypal personality traits in healthy subjects. METHODS: Twenty young male
      subjects underwent 2 all-night sleep electroencephalography recordings (128
      electrodes). Sleep spindles were detected automatically. After those 2 nights,
      thalamic Glx levels were measured by magnetic resonance spectroscopy. Subjects
      completed a magical ideation scale to assess schizotypy. RESULTS: Sleep spindle
      density was negatively correlated with magical ideation (r = -.64, P < .01) and
      thalamic Glx levels (r = -.70, P < .005). No correlation was found between Glx
      levels in the thalamus and magical ideation (r = .12, P > .1). CONCLUSIONS: The
      common relationship of sleep spindle density with schizotypy and thalamic Glx
      levels indicates a neurobiological overlap between nonclinical schizotypy and
      schizophrenia. Thus, sleep spindle density and magical ideation may reflect the
      anatomy and efficiency of the thalamo-cortical system that shows pronounced
      impairment in patients with schizophrenia.

PMID- 25074978
TI  - The COP II adaptor protein TMED7 is required to initiate and mediate the delivery
      of TLR4 to the plasma membrane.
AB  - Toll-like receptor 4 (TLR4), the receptor for the bacterial product endotoxin, is
      subject to multiple points of regulation at the levels of signaling, biogenesis,
      and trafficking. Dysregulation of TLR4 signaling can cause serious inflammatory
      diseases, such as sepsis. We found that the p24 family protein TMED7
      (transmembrane emp24 protein transport domain containing 7) is required for the
      trafficking of TLR4 from the endoplasmic reticulum to the cell surface through
      the Golgi. TMED7 formed a stable complex with the ectodomain of TLR4, an
      interaction that required the coiled-coil and Golgi dynamics (GOLD) domains, but
      not the cytosolic, coat protein complex II (COP II) sorting motif, of TMED7.
      Depletion of TMED7 reduced TLR4 signaling mediated by the adaptor protein MyD88
      (myeloid differentiation marker 88), but not that mediated by the adaptor
      proteins TRIF [Toll-interleukin-1 receptor (TIR) domain-containing adaptor
      protein inducing interferon-beta] and TRAM (TRIF-related adaptor molecule).
      Truncated forms of TMED7 lacking the COP II sorting motif or the transmembrane
      domain were mislocalized and resulted in ligand-independent signaling that
      probably arises from receptors accumulated intracellularly. Together, these
      results support the hypothesis that p24 proteins perform a quality control step
      by recognizing correctly folded anterograde cargo, such as TLR4, in early
      secretory compartments and facilitating the translocation of this cargo to the
      cell surface. 

PMID- 25074980
TI  - Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the
      cell surface for lymphocyte trafficking.
AB  - In lymphocytes, the kinase Mst1 is required for the proper organization of
      integrins in the plasma membrane at the leading edge of migrating cells, which is
      critical for lymphocyte trafficking. We found a functional link between the small
      G protein Rab13 and Mst1 in lymphocyte adhesion and migration. In response to
      stimulation of T lymphocytes with chemokine, Mst1 promoted phosphorylation of the
      guanine nucleotide exchange factor DENND1C (differentially expressed in normal
      and neoplastic cells domain 1C), which activated Rab13. Active Rab13 associated
      with Mst1 to facilitate the delivery of the integrin LFA-1 (lymphocyte function
      associated antigen 1) to the leading edge of lymphocytes. Delivery of LFA-1
      involved the recruitment of myosin Va along actin filaments, which extended as a
      result of the localization of the actin regulatory protein VASP to the cell
      periphery through phosphorylation of VASP at Ser(157) by Mst1. Inhibition of
      Rab13 function reduced the adhesion and migration of lymphocytes on ICAM-1
      (intercellular adhesion molecule-1), the ligand for LFA-1, and inhibited the
      formation of a ring-like arrangement of LFA-1 at the contact sites between T
      cells and antigen-presenting cells. The lymphoid tissues of Rab13-deficient mice
      had reduced numbers of lymphocytes because of the defective trafficking
      capability of these cells. These results suggest that Rab13 acts with Mst1 to
      regulate the spatial distribution of LFA-1 and the motility and trafficking of
      lymphocytes. 

PMID- 25074979
TI  - MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis
      and trastuzumab resistance in breast cancer.
AB  - Sirtuin 6 (SIRT6) is associated with longevity and is also a tumor suppressor.
      Identification of molecular regulators of SIRT6 might enable its activation
      therapeutically in cancer patients. In various breast cancer cell lines, we found
      that SIRT6 was phosphorylated at Ser(338) by the kinase AKT1, which induced the
      interaction and ubiquitination of SIRT6 by MDM2, targeting SIRT6 for protease
      dependent degradation. The survival of breast cancer patients positively
      correlated with the abundance of SIRT6 and inversely correlated with the
      phosphorylation of SIRT6 at Ser(338). In a panel of breast tumor biopsies, SIRT6
      abundance inversely correlated with the abundance of phosphorylated AKT.
      Inhibiting AKT or preventing SIRT6 phosphorylation by mutating Ser(338) prevented
      the degradation of SIRT6 mediated by MDM2, suppressed the proliferation of breast
      cancer cells in culture, and inhibited the growth of breast tumor xenografts in
      mice. Overexpressing MDM2 decreased the abundance of SIRT6 in cells, whereas
      overexpressing an E3 ligase-deficient MDM2 or knocking down endogenous MDM2
      increased SIRT6 abundance. Trastuzumab (known as Herceptin) is a drug that
      targets a specific receptor common in some breast cancers, and knocking down
      SIRT6 increased the survival of a breast cancer cell exposed to trastuzumab.
      Overexpression of a nonphosphorylatable SIRT6 mutant increased trastuzumab
      sensitivity in a resistant breast cancer cell line. Thus, stabilizing SIRT6 may
      be a clinical strategy for overcoming trastuzumab resistance in breast cancer
      patients. 

PMID- 25074982
TI  - Experience with oral betamethasone in extremely low birthweight infants with
      bronchopulmonary dysplasia.

PMID- 25074981
TI  - Influence of skin colour on diagnostic accuracy of the jaundice meter JM 103 in
      newborns.
AB  - AIM: To assess the diagnostic accuracy of the JM 103 as a screening tool for
      neonatal jaundice and explore differential effects based on skin colour. METHODS:
      We prospectively compared the transcutaneous bilirubin (TcB) and serum bilirubin
      (TSB) measurements of newborns over a 3 month-period. Skin colour was assigned
      via reference colour swatches. Diagnostic measures of the TcB/TSB comparison were
      made and clinically relevant TcB cut-off values were determined for each skin
      colour group. RESULTS: 451 infants (51 light, 326 medium and 74 dark skin colour)
      were recruited. The association between TcB and TSB was high for all skin colours
      (rs>0.9). The Bland-Altman analysis showed an absolute mean difference between
      the two measures of 13.3+/-26.4 umol/L with broad limits of agreement (-39.4-66.0
      umol/L), with TcB underestimating TSB in light and medium skin colours and
      overestimating in dark skin colour. Diagnostic measures were also consistently
      high across skin colours, with no clinically significant differences observed.
      CONCLUSIONS: The JM 103 is a useful screening tool to identify infants in need of
      serum bilirubin, regardless of skin colour. The effect of skin colour on the
      accuracy of this device at high levels of serum bilirubin could not be assessed
      fully due to small numbers in the light and dark groups.

PMID- 25074983
TI  - Activation of growth hormone secretagogue receptor induces time-dependent clock
      phase delay in mice.
AB  - Early studies have reported a phase-shifting effect of growth hormone
      secretagogues (GHSs). This study aimed to determine the mechanism of action of
      GHSs. We examined the response of the hypothalamic suprachiasmatic nuclei (SCN)
      to growth hormone releasing peptide-6 (GHRP-6) by assessing effects on the phase
      of locomotor activity rhythms, SCN neuronal discharges, and the potential
      signaling pathways involved in the drug action on circadian rhythms. The results
      showed that bolus administration of GHRP-6 (100 MUg/kg ip) at the beginning of
      subjective night (CT12) induced a phase delay of the free-running rhythms in male
      C57BL/6J mice under constant darkness, but did not elicit phase shift at other
      checked circadian time (CT) points. The phase-delay effect of GHRP-6 was
      abolished by d-(+)-Lys-GHRP-6 (GHS receptor antagonist), KN-93
      [calcium/calmodulin-dependent protein kinase II (CaMK) II inhibitor], or anti
      phosphorylated (p)-cAMP response element-binding protein (CREB) antibody. Further
      analyses demonstrated that GHRP-6 at CT12 induced higher calcium mobilization and
      neuronal discharge in the SCN compared with that at CT6, decreased the levels of
      glutamate and gamma-aminobutyric acid, increased the levels of p-CaMKII, p-CREB,
      and period 1, and delayed the circadian expressions of circadian locomotor output
      cycles kaput, Bmal1, and prokineticin 2 in the SCN; these signaling changes
      resulted in behavioral phase delay. Collectively, GHRP-6 induces a CT-dependent
      phase delay via activating GHS receptor and the downstream signaling, which is
      partially similar to the signaling cascade of light-induced phase delay at early
      night. These novel observations may help to better understand the role of GHSs in
      circadian physiology. 

PMID- 25074984
TI  - Testosterone alters iron metabolism and stimulates red blood cell production
      independently of dihydrotestosterone.
AB  - Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis.
      However, it remains unknown whether the (type II) 5alpha-reduction of T to
      dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some
      other tissues. Our purpose was to determine whether inhibition of type II 5alpha
      reductase (via finasteride) alters red blood cell (RBC) production and serum
      markers of iron homeostasis subsequent to testosterone-enanthate (TE)
      administration in older hypogonadal men. Sixty men aged >=60 yr with serum T <300
      ng/dl or bioavailable T <70 ng/dl received treatment with TE (125 mg/wk) vs.
      vehicle paired with finasteride (5 mg/day) vs. placebo using a 2 * 2 factorial
      design. Over the course of 12 mo, TE increased RBC count 9%, hematocrit 4%, and
      hemoglobin 8% while suppressing serum hepcidin 57% (P < 0.001 for all
      measurements). Most of the aforementioned changes occurred in the first 3 mo of
      treatment, and finasteride coadministration did not significantly alter any of
      these effects. TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of
      treatment initiation without altering iron, transferrin, or transferrin
      saturation. We conclude that TE stimulates erythropoiesis and alters iron
      homeostasis independently of the type II 5alpha-reductase enzyme. These results
      demonstrate that elevated DHT is not required for androgen-mediated
      erythropoiesis or for alterations in iron homeostasis that would appear to
      support iron incorporation into RBCs. 

PMID- 25074985
TI  - Effects of delayed gastric emptying on postprandial glucose kinetics, insulin
      sensitivity, and beta-cell function.
AB  - Controlling meal-related glucose excursions continues to be a therapeutic
      challenge in diabetes mellitus. Mechanistic reasons for this need to be
      understood better to develop appropriate therapies. To investigate delayed
      gastric emptying effects on postprandial glucose turnover, insulin sensitivity,
      and beta-cell responsivity and function, as a feasibility study prior to studying
      patients with type 1 diabetes, we used the triple tracer technique C-peptide and
      oral minimal model approach in healthy subjects. A single dose of 30 MUg of
      pramlintide administered at the start of a mixed meal was used to delay gastric
      emptying rates. With delayed gastric emptying rates, peak rate of meal glucose
      appearance was delayed, and rate of endogenous glucose production (EGP) was
      lower. C-peptide and oral minimal models enabled the assessments of beta-cell
      function, insulin sensitivity, and beta-cell responsivity simultaneously. Delayed
      gastric emptying induced by pramlintide improved total insulin sensitivity and
      decreased total beta-cell responsivity. However, beta-cell function as measured
      by total disposition index did not change. The improved whole body insulin
      sensitivity coupled with lower rate of appearance of EGP with delayed gastric
      emptying provides experimental proof of the importance of evaluating pramlintide
      in artificial endocrine pancreas approaches to reduce postprandial blood glucose
      variability in patients with type 1 diabetes. 

PMID- 25074986
TI  - (Pro)renin receptor in skeletal muscle is involved in the development of insulin
      resistance associated with postinfarct heart failure in mice.
AB  - We previously reported that insulin resistance was induced by the impairment of
      insulin signaling in the skeletal muscle from heart failure (HF) via NAD(P)H
      oxidase-dependent oxidative stress. (Pro)renin receptor [(P)RR] is involved in
      the activation of local renin-angiotensin system and subsequent oxidative stress.
      We thus examined whether (P)RR inhibitor, handle region peptide (HRP), could
      ameliorate insulin resistance in HF after myocardial infarction (MI) by improving
      oxidative stress and insulin signaling in the skeletal muscle. C57BL6J mice were
      divided into four groups: sham operated (Sham, n = 10), Sham treated with HRP
      (Sham+HRP, 0.1 mg.kg(-1).day(-1), n = 10), MI operated (MI, n = 10), and MI
      treated with HRP (MI+HRP, 0.1 mg/kg/day, n = 10). After 4 wk, MI mice showed left
      ventricular dysfunction, which was not affected by HRP. (P)RR was upregulated in
      the skeletal muscle after MI (149% of sham, P < 0.05). The decrease in plasma
      glucose after insulin load was smaller in MI than in Sham (21 +/- 2 vs. 44 +/-
      3%, P < 0.05), and was greater in MI+HRP (38 +/- 2%, P < 0.05) than in MI.
      Insulin-stimulated serine phosphorylation of Akt and glucose transporter 4
      translocation were decreased in the skeletal muscle from MI by 48 and 49% of
      Sham, both of which were ameliorated in MI+HRP. Superoxide production and NAD(P)H
      oxidase activities were increased in MI, which was inhibited in MI+HRP. HRP
      ameliorated insulin resistance associated with HF by improving insulin signaling
      via the inhibition of NAD(P)H oxidase-induced superoxide production in the
      skeletal muscle. The (P)RR pathway is involved in the development of insulin
      resistance, at least in part, via the impairment of insulin signaling in the
      skeletal muscle from HF. 

PMID- 25074987
TI  - FOXO1 activates glutamine synthetase gene in mouse skeletal muscles through a
      region downstream of 3'-UTR: possible contribution to ammonia detoxification.
AB  - Skeletal muscle is a reservoir of energy in the form of protein, which is
      degraded under catabolic conditions, resulting in the formation of amino acids
      and ammonia as a byproduct. The expression of FOXO1, a forkhead-type
      transcription factor, increases during starvation and exercise. In agreement,
      transgenic FOXO1-Tg mice that overexpress FOXO1 in skeletal muscle exhibit muscle
      atrophy. The aim of this study was to examine the role of FOXO1 in amino acid
      metabolism. The mRNA and protein expressions of glutamine synthetase (GS) were
      increased in skeletal muscle of FOXO1-Tg mice. Fasting induced FOXO1 and GS
      expression in wild-type mice but hardly increased GS expression in muscle
      specific FOXO1 knockout (FOXO1-KO) mice. Activation of FOXO1 also increased GS
      mRNA and protein expression in C2C12 myoblasts. Using a transient transfection
      reporter assay, we observed that FOXO1 activated the GS reporter construct.
      Mutation of a putative FOXO1-binding consensus sequence in the downstream genomic
      region of GS decreased basal and FOXO1-dependent reporter activity significantly.
      A chromatin immunoprecipitation assay showed that FOXO1 was recruited to the 3'
      region of GS in C2C12 myoblasts. These results suggest that FOXO1 directly
      upregulates GS expression. GS is considered to mediate ammonia clearance in
      skeletal muscle. In agreement, an intravenous ammonia challenge increased blood
      ammonia concentrations to a twofold higher level in FOXO1-KO than in wild-type
      mice, demonstrating that the capacity for ammonia disposal correlated inversely
      with the expression of GS in muscle. These data indicate that FOXO1 plays a role
      in amino acid metabolism during protein degradation in skeletal muscle. 

PMID- 25074989
TI  - Temporal and other factors that influence the time doctors take to prescribe
      using an electronic prescribing system.
AB  - BACKGROUND: A computerized physician order entry (CPOE) system with embedded
      clinical decision support can reduce medication errors in hospitals, but might
      increase the time taken to generate orders. AIMS: We aimed to quantify the
      effects of temporal (month, day of week, hour of shift) and other factors (grade
      of doctor, prior experience with the system, alert characteristics, and shift
      type) on the time taken to generate a prescription order. SETTING: A large
      university teaching hospital using a locally developed CPOE system with an
      extensive audit database. DESIGN: We retrospectively analyzed prescription orders
      from the audit database between August 2011 and July 2012. RESULTS: The geometric
      mean time taken to generate a prescription order within the CPOE system was 11.75
      s (95% CI 11.72 to 11.78). Time to prescribe was most affected by the display of
      high-level (24.59 s (24.43 to 24.76); p<0.001) or previously unseen (18.87 s
      (18.78 to 18.96); p<0.001) alerts. Prescribers took significantly less time at
      weekends (11.29 s (11.23 to 11.35)) than on weekdays (11.88 s (11.84 to 11.91);
      p<0.001), in the first (11.25 s (11.16 to 11.34); p<0.001) and final (11.56 s
      (11.47 to 11.66); p<0.001) hour of their shifts, and after the first month of
      using the system. CONCLUSIONS: The display of alerts, prescribing experience,
      system familiarity, and environment all affect the time taken to generate a
      prescription order. Our study reinforces the need for appropriate alerts to be
      presented to individuals at an appropriate place in the workflow, in order to
      improve prescribing efficiency.

PMID- 25074988
TI  - Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely
      burned adults.
AB  - Elevated metabolic rate is a hallmark of the stress response to severe burn
      injury. This response is mediated in part by adrenergic stress and is responsive
      to changes in ambient temperature. We hypothesize that uncoupling of oxidative
      phosphorylation in skeletal muscle mitochondria contributes to increased
      metabolic rate in burn survivors. Here, we determined skeletal muscle
      mitochondrial function in healthy and severely burned adults. Indirect
      calorimetry was used to estimate metabolic rate in burn patients. Quadriceps
      muscle biopsies were collected on two separate occasions (11 +/- 5 and 21 +/- 8
      days postinjury) from six severely burned adults (68 +/- 19% of total body
      surface area burned) and 12 healthy adults. Leak, coupled, and uncoupled
      mitochondrial respiration was determined in permeabilized myofiber bundles.
      Metabolic rate was significantly greater than predicted values for burn patients
      at both time points (P < 0.05). Skeletal muscle oxidative capacity, citrate
      synthase activity, a marker of mitochondrial abundance, and mitochondrial
      sensitivity to oligomycin were all lower in burn patients vs. controls at both
      time points (P < 0.05). A greater proportion of maximal mitochondrial respiration
      was linked to thermogenesis in burn patients compared with controls (P < 0.05).
      Increased metabolic rate in severely burned adults is accompanied by derangements
      in skeletal muscle mitochondrial function. Skeletal muscle mitochondria from burn
      victims are more uncoupled, indicating greater heat production within skeletal
      muscle. Our findings suggest that skeletal muscle mitochondrial dysfunction
      contributes to increased metabolic rate in burn victims. 

PMID- 25074990
TI  - Two cases of spuriously elevated cerebrospinal glucose concentration.
AB  - We present two cases of spuriously high cerebrospinal fluid glucose concentration
      with approximately normal blood glucose concentrations. The cause of these
      abnormal findings was the use of inappropriate collection tubes during the pre
      analytical phase. Whilst no patient harm was identified following this error,
      significant time and effort were expended by both laboratory and clinical staff
      to explain the cause of these findings. 

PMID- 25074991
TI  - Reference ranges for serum total and monomeric prolactin for the current
      generation Abbott Architect assay.
AB  - BACKGROUND: Exclusion of macroprolactinaemia, a well-recognised interference, as
      the cause of hyperprolactinaemia is essential to avoid potential misdiagnosis and
      mismanagement of patients. We have derived gender-specific serum total and post
      polyethylene glycol (PEG) precipitation monomeric reference ranges for the
      recently re-standardised Abbott Architect prolactin assay. METHODS: Prolactin was
      measured in serum samples obtained from males (n=49) and females (n=52) using the
      current Abbott Architect immunoassay pre- and post-PEG precipitation. Gender
      specific reference ranges were derived for total and monomeric (post-PEG)
      prolactin. Routine patients' samples (n=175) with a serum total prolactin >700
      mIU/L were screened for macroprolactinaemia to assess classification compared
      with our previous post-PEG precipitation percentage recovery-based approach.
      RESULTS: Reference ranges for serum total prolactin were 58-419 mIU/L (male) and
      63-561 mIU/L (female). Male and female monomeric prolactin reference ranges were
      32-309 mIU/L and 39-422 mIU/L, respectively. Mean (SD) post-PEG percentage
      recovery of the IS 84/500 prolactin standard was 80 (2.3)%. Of 175 patients'
      samples screened for macroprolactinaemia, 149 had monomeric prolactin
      concentrations (median monomeric prolactin=1035 mIU/L; median recovery=83%) above
      the gender-specific reference range. Monomeric prolactin concentrations (median
      monomeric prolactin=162 mIU/L; median recovery=20%) in the remaining 26 were
      within the reference ranges. One patient classified as macroprolactin positive
      and another classified as macroprolactin negative would not have been identified
      as such using the previous recovery-based approach. CONCLUSIONS: The use of post
      PEG monomeric reference ranges not only identifies hyperprolactinaemia due solely
      to macroprolactinaemia but has the added advantage of identifying patients who
      have simultaneous true monomeric hyperprolactinaemia and elevated concentrations
      of macroprolactin.

PMID- 25074992
TI  - The role of peritoneal dialysis in Saving Young Lives from acute kidney injury.

PMID- 25074993
TI  - Genome-wide methylation and body-mass index.

PMID- 25074994
TI  - Peritoneal dialysis, acute kidney injury, and the Saving Young Lives program.

PMID- 25074995
TI  - Peritoneal dialysis for acute kidney injury.

PMID- 25074996
TI  - Continuous ambulatory peritoneal dialysis in Limpopo province, South Africa:
      predictors of patient and technique survival.
AB  - ? INTRODUCTION AND AIM: Continuous ambulatory peritoneal dialysis (CAPD) is not a
      frequently used modality of dialysis in many parts of Africa due to several socio
      economic factors. Available studies from Africa have shown a strong association
      between outcome and socio-demographic variables. We sought to assess the outcome
      of patients treated with CAPD in Limpopo, South Africa. ? METHODS: This was a
      retrospective study of 152 patients treated with CAPD at the Polokwane Kidney and
      Dialysis Centre (PKDC) from 2007 to 2012. We collected relevant demographic and
      biochemical data for all patients included in the study. A composite outcome of
      death while still on peritoneal dialysis (PD) or CAPD technique failure from any
      cause requiring a change of modality to hemodialysis (HD) was selected. The
      peritonitis rate and causes of peritonitis were assessed from 2008 when all
      related data could be obtained. ? RESULTS: There were 52% males in the study and
      the average age of the patients was 36.8 +/- 11.4 years. Unemployment rate was
      high (71.1%), 41.1% had tap water at home, the average distance travelled to the
      dialysis center was 122.9 +/- 78.2 kilometres and half the patients had a total
      income less than USD ($)180 per month. Level of education, having electricity at
      home, having tap water at home, body mass index (BMI), serum albumin and
      hemoglobin were significantly different between those reaching the composite
      outcome and those not reaching it (p < 0.05). The overall peritonitis rate was
      0.82/year with 1-year, 2-year and 5-year survival found to be 86.7%, 78.7% and
      65.3% (patient survival) and 83.3%, 71.7% and 62.1% (technique survival).
      Predictors of the composite outcome were BMI (p = 0.011), serum albumin (p =
      0.030), hemoglobin (p = 0.002) and more than 1 episode of peritonitis (p =
      0.038). ? CONCLUSION: Treatment of anemia and malnutrition as well as training
      and re-training of CAPD patients and staff to prevent recurrence of peritonitis
      can have positive impacts on CAPD outcomes in this population.

PMID- 25074997
TI  - Effect of peritoneal dialysis on respiratory mechanics in acute kidney injury
      patients.

PMID- 25074998
TI  - Is there need of an extension channel/new double-cuffed channel in surgical
      management for channel perforation and aneurysm of Tenckhoff catheter?: modified
      partial replantation.

PMID- 25074999
TI  - Percutaneous and surgical peritoneal dialysis catheter placements have comparable
      outcomes in the modern era.

PMID- 25075000
TI  - New peritoneal catheters: new catheter problems?

PMID- 25075001
TI  - Gadolinium deposits could influence the course of encapsulating peritoneal
      sclerosis.

PMID- 25075002
TI  - Successful peritoneal dialysis in 2 siblings with Alport's disease and gastric
      pull-up.

PMID- 25075003
TI  - Fusarium peritonitis successfully managed with posaconazole and catheter removal.

PMID- 25075004
TI  - Providencia rettgeri peritonitis in a patient on peritoneal dialysis with
      perforated appendicitis.

PMID- 25075005
TI  - Role of primary care physicians in treating patients with ST-segment elevation
      myocardial infarction located in remote areas (from the REseau Nord-Alpin des
      Urgences [RENAU], Network).
AB  - BACKGROUND: European guidelines for ST-segment elevation myocardial infarction
      (STEMI) encourage healthcare networks to increase rates of, and decrease delays
      to, reperfusion. We examined the impact of training primary care physicians
      (PCPs) to use equipment for pre-hospital management of STEMI patients in remote
      areas. METHODS AND RESULTS: A network for cardiac emergencies was set up in the
      French Northern Alps in 2002 and a registry of STEMI patients has been kept
      since. In 2005, 24 local volunteer PCPs were trained and equipped with
      electrocardiograms, fibrinolysis kits, and automated external defibrillators to
      deal with cardiac emergencies in remote areas (>30-minute ambulance travelling
      time). In this study, when the central call dispatcher received a telephone call
      from a patient in a remote area reporting chest pain with a high probability of
      STEMI, the dispatcher sent a mobile intensive care unit (MICU) with an emergency
      physician on board and asked the local PCP, if available, to manage the patient
      while awaiting arrival of the MICU. Patients in whom the diagnosis of STEMI was
      confirmed were taken by MICU to an interventional cardiology hospital. We report
      on patients who received care from a PCP before arrival of the MICU. Between 2005
      and 2010, 4,015 patients were enrolled in the registry; 180 patients were located
      in a remote area, of whom 140 were in an area covered by a participating PCP. Of
      the 62 patients attended by a PCP before MICU arrival, 27 received thrombolysis
      and eight patients with ventricular tachycardia/fibrillation were shocked with an
      automated external defibrillator by the PCP. Mean times from telephone call to
      thrombolysis were shorter when the patient was attended by a PCP (45.0 +/- 25.5
      vs 62.4 +/- 23.4 min without intervention; p = 0.003). STEMI diagnosis without
      contraindication to thrombolysis was confirmed in 26 of 27 patients treated as
      such by PCPs and 1 patient was diagnosed with a Tako-Tsubo syndrome. CONCLUSION:
      PCP care of STEMI patients located in isolated areas appears efficient, with high
      rates of resuscitation and thrombolysis and a shorter delay to reperfusion.

PMID- 25075007
TI  - The RECK gene and biological malignancy--its significance in angiogenesis and
      inhibition of matrix metalloproteinases.
AB  - The RECK (reversion-inducing cysteine-rich protein with Kazal motifs) gene is a
      relatively newly discovered gene with important implications in cancer biology.
      RECK is normally expressed in all cells of the body and has an important role in
      the balance between destructive and constructive features of the extracellular
      matrix (ECM). The RECK protein is a membrane-bound glycoprotein that inhibits
      matrix metalloproteinases with the function of breaking-down the ECM. There is a
      significant correlation between RECK gene expression and the formation of new
      vessels, presumably via the mediation of vascular endothelial growth factor
      (VEGF), which is an important and powerful inducer of angiogenesis. Research has
      shown that down-regulation of RECK is caused by the rat sarcoma oncogene (RAS),
      which is also a common cause of tumor development in the early stages. For a
      tumor to progress and gain characteristics that classifies it as malignant, the
      degradation of the ECM and mobilization of new blood vessels are essential
      functions. If the tumor is inhibited with respect to these functions, it will
      cease to grow. RECK is, therefore, a potential tumor inhibitor but also a
      prognostic marker available at early clinical stages. 

PMID- 25075006
TI  - Impact of fondaparinux versus enoxaparin on in-hospital bleeding and 1-year death
      in non-ST-segment elevation myocardial infarction. FAST-MI (French Registry of
      Acute ST-elevation and non-ST-elevation Myocardial Infarction) 2010.
AB  - AIMS: Fondaparinux is an alternative to low molecular weight heparin (LMWH) for
      non-ST-elevation myocardial infarction (NSTEMI) with levels of recommendation
      that differ according to guidelines. The aim of this study was to assess outcomes
      in real world practice in NSTEMI patients participating in the French Registry of
      ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 according
      to the use of fondaparinux, in comparison with patients receiving enoxaparin.
      METHODS AND RESULTS: FAST-MI 2010 is a nationwide French registry that included
      4,169 patients with acute myocardial infarction at the end of 2010 in 213 centres
      (76% of active centres in France); 1,734 had NSTEMI, with 240 receiving
      fondaparinux and 1,027 enoxaparin. Patients receiving enoxaparin vs. fondaparinux
      had essentially characteristics with a similar GRACE (Global Registry of Acute
      Coronary Events) score. Invasive strategy was used in 69% in both groups. In
      hospital bleeding was similar with both anticoagulant strategies and 1-year
      survival was 94.6% and 91.7%, respectively. Using fully adjusted Cox multivariate
      analysis, the use of fondaparinux was not associated with a reduced risk of death
      (hazard ratio: 1.35; 95% confidence interval: 0.70-2.51). After propensity score
      matching (207 patients per group), 1-year survival was similar with both
      strategies. There was, however, an interaction between fondaparinux and
      unfractionated heparin, with higher survival in fondaparinux-treated patients who
      received UFH, compared with those who did not. CONCLUSIONS: In this French cohort
      of NSTEMI patients, predominantly managed invasively, there was no evidence that
      fondaparinux was superior to enoxaparin as regards bleeding events or 1-year
      mortality (FAST-MI 2010; NCT01237418).

PMID- 25075008
TI  - Alterations in gene expression during radiation-induced mitotic catastrophe in
      HeLa Hep2 cells.
AB  - AIM: To explore kinetic changes in the gene expression profile during radiation
      induced mitotic catastrophes. MATERIALS AND METHODS: Gene expression changes were
      measured in HPV-infected HeLa Hep2 tumor cells following exposure to 5 Gy of
      ionizing radiation ((60)Co). Signaling pathways were explored and correlated to
      the biological responses linked to mitotic catastrophe. RESULTS: Following
      irradiation a transient G2-arrest was induced. Anaphase bridge formation and
      centrosome hyperamplification was observed. These phenotypical changes correlated
      well with the observed gene expression changes. Genes with altered expression
      were found to be involved in mitotic processes as well as G2- and spindle
      assembly checkpoints. Also centrosome-associated genes displayed an increased
      expression. CONCLUSION: This study elucidates specific characteristics in the
      altered gene expression pattern induced by irradiation, which can be correlated
      to the events of mitotic catastrophe in HeLa Hep2 cells. Therapeutic strategies
      modulating these alterations might potentiate future therapy and enhance tumor
      cell killing.

PMID- 25075009
TI  - Worse prognosis of osteosarcoma patients expressing IGF-1 on a tissue microarray.
AB  - BACKGROUND: It is hardly possible to define osteosarcoma (OS) patients at
      greatest risk for non-response to chemotherapy, metastasis and short survival
      times. Our goal was the investigation of local expression of insulin-like growth
      factor (IGF-1) with regard to survival time of OS patients using a tissue
      microarray (TMA). MATERIALS AND METHODS: Tumor tissue specimens from surgical
      primary tumor resections were collected from patients with OS. A TMA was
      composed, sections were stained with rabbit anti-IGF-1 and grading was performed.
      Statistics involved Kaplan-Meier curves and the log-rank test. RESULTS: We
      analyzed immunohistochemical expression of local IGF-1 on a TMA based on surgical
      primary tumor resections of 67 OS patients. The mean clinical follow-up time was
      98 months. Twenty-two (33%) OS patients stained negatively and 44 (66%) OS
      patients stained positively for IGF-1. Significantly shorter survival was
      detected with expression of IGF-1 (p=0.007). The 5-year survival rate for
      patients expressing IGF-1 was 63% compared to 92% in patients without expression
      of IGF-1. Non-responders to chemotherapy and patients with metastasis, who also
      stained positively for IGF-1 manifested a significantly (p=0.002 and p<0.0001,
      respectively) shorter survival. CONCLUSION: Expression of local IGF-1 in primary
      tumor tissue appears to significantly affect the aggressiveness of OS, may
      predict survival time and, above all, may discriminate patients with non-response
      to chemotherapy and metastasis. This represents the basis for successful patient
      selection with regard to the decision process for or against chemotherapy and the
      choice of the most effective therapeutic drug. It may be a more important marker
      of tumor progression and indicator of prognosis than serum IGF-1. Novel tumor
      markers and therapeutic agents targeting the local IGF-1 pathway may increase the
      likelihood of therapeutic success.

PMID- 25075011
TI  - Analysis of MUC4 expression in human pancreatic cancer xenografts in
      immunodeficient mice.
AB  - BACKGROUND/AIM: Mucin 4 (MUC4) is a cell surface glycoprotein that is
      overexpressed in most pancreatic tumors. The aim of the present study was to
      characterize MUC4 expression in experimental pancreatic cancer in order to
      clarify the correlation between MUC4 and pancreatic cancer histology in vivo.
      MATERIALS AND METHODS: Pancreatic xenograft tumors were generated in
      immunodeficient mice (n=15) by subcutaneous injection of MUC4(+) human pancreatic
      cancer cell lines Capan-1, HPAF-II or CD18/HPAF. MUC4 immunoreactivity was
      compared between the cancer models. Alpha-smooth muscle actin (alpha-SMA) was
      used to identify cancer-associated fibroblasts and the amount of collagen fibers
      was quantified with sirius red. RESULTS: Tumor incidence was 100%. Tumor size
      showed no difference across groups (p=0.796). The median MUC4 count was highest
      in Capan-1 tumors (p=0.002). alpha-SMA and collagen extent were also highest in
      Capan-1 tumors (p=0.018). CONCLUSION: The Capan-1 xenograft model could serve as
      a valuable resource to test new therapeutic strategies targeting MUC4 in
      pancreatic cancer.

PMID- 25075010
TI  - Benzimidazole analogs as potent hypoxia inducible factor inhibitors: synthesis,
      biological evaluation, and profiling drug-like properties.
AB  - AIM: To develop potent HIF-1alpha inhibitors for potential treatment of cancer.
      MATERIALS AND METHODS: Chemical synthesis, HIF-luciferase assay, cytotoxic assay,
      platelet aggregation assay, western blot analysis, quantitative real-time PCR,
      aqueous solubility, protein binding, metabolic stability, and metabolic pathways.
      RESULTS: Thirteen novel benzimidazole analogs were synthesized. Compounds 3a and
      3k showed the highest anti-HIF-1alpha activity. They are significantly more
      effective than YC-1 in the suppression of HIF-1alpha protein expression based on
      western blot assay. They show comparable potency in inhibition of cancer cell
      migration. They are less potent in the inhibition of platelet aggregation. 3k had
      the most favorable drug-like properties, including long half-life in human liver
      microsomes, medium protein binding level and reasonable aqueous solubility.
      CONCLUSION: The potent anti-HIF-1alpha activity and favorable drug-like
      properties of compound 3k suggest that it may hold great potential as an adjuvant
      therapy for cancer treatment through repression of HIF-1alpha protein expression.

PMID- 25075012
TI  - Intratumoral lymphangiogenesis and prognostic significance of VEGFC expression in
      gastric cancer.
AB  - AIM: Vascular endothelial growth factor C (VEGFC) is thought to promote
      lymphangiogenesis in various human cancer tissues. MATERIALS AND METHODS: The
      present study analyzed data from 72 patients with gastric cancer. The lymphatic
      vessel density (LVD) was determined by immunohistochemical staining using a
      monoclonal antibody (mAb) against D2-40, and the expression of VEGFC was
      investigated using a mAb against VEGFC. RESULTS: The intratumoral LVD was higher
      in cases with nodal metastasis. The VEGFC-positive cases had a higher
      intratumoral LVD and were more invasive to the lymphatic vessels or lymph nodes
      than negative cases. Patients with VEGFC-positive cancer had significantly lower
      survival than those with negative cancer (p<0.05). CONCLUSION: The expression of
      VEGFC was related to intratumoral lymph angiogenesis and serves as a pertinent
      predictive factor for lymphatic invasion or metastasis, while also providing
      prognostic value.

PMID- 25075013
TI  - Tumor regression by CD4 T-cells primed with dendritic/tumor fusion cell vaccines.
AB  - BACKGROUND/AIM: Vaccination with fusions of dendritic cells (DCs) and mucin-1
      (MUC1)-positive tumor cells (FC/MUC1) induces MUC1-specific antitumor immunity.
      However, little is known about the function of Cluster of Differentiation (CD)4 T
      cells primed with FC/MUC1 in MUC1 transgenic (MUC1.Tg) mice. MATERIALS AND
      METHODS: CD4 T-cells primed with FC/MUC1 were analyzed by flow cytometry.
      Antitumor immunity by adoptive transfer of primed CD4 T-cells in Rag2(-/-) mice
      was assessed. RESULTS: The effector and memory T-cells generated with FC/MUC1
      were crucial to maintenance of long-term antitumor immunity. MUC1-8-mer peptide
      SAPDTRPA presented by FC/MUC1 was recognized by CD4 and CD8 T-cells. A subset of
      primed CD4 T-cells possessed cytotoxicity to lyse major histocompatibility
      complex (MHC) class I and MUC1 positive tumor cells. Interestingly, adoptive
      transfer of primed CD4 T-cells prevented lung metastasis in Rag2(-/-) mice.
      CONCLUSION: CD4 T-cells primed by FC/MUC1 play direct role in antitumor immunity.

PMID- 25075014
TI  - Optimal production of a fusion protein consisting of a single-chain variable
      fragment antibody against a tumor-associated antigen and interleukin-2 in fed
      batch culture of Pichia pastoris.
AB  - BACKGROUND/AIM: The aim of the present study was to establish the strategy for
      producing a single-chain variable fragment (scFv) antibody fused with interleulin
      2 (IL2) by Pichia pastoris and to optimize production during fed-batch
      cultivation in a 5-l fermenter. MATERIALS AND METHODS: We constructed a fusion
      sequence consisting of an scFv gene derived from a mouse monoclonal antibody
      against a tumor-associated antigen (designated MK-1 antigen) and human
      interleulin-2 (IL-2) gene, ligated the sequences to expression vector pPICZalpha
      A and separately transformed the constructs into Pichia pastoris strains GS115
      and KM71H. RESULTS: The highest concentration of secreted fusion protein, 738 +/-
      44 mg/l, was obtained after a 60-h induction. To investigate the specific binding
      activity of the partially purified fusion protein, we used an enzyme-linked
      immunosorbent assay and antigen from a whole-cell lysate. Student's t-test showed
      that the specific binding activity of the partially-purified fusion protein to
      the lysate of Chinese hamster ovary cell lines expressing the MK-1 antigen was
      significantly higher than that of the lysate of CHO cell lines that do not
      express MK-1. CONCLUSIONS: The method described here permits the production of
      substantial amounts of the fusion protein for conducting functional studies on
      the biological role of these fusion proteins.

PMID- 25075015
TI  - High expression of fusion proteins consisting of a single-chain variable fragment
      antibody against a tumor-associated antigen and interleukin-2 in Escherichia
      coli.
AB  - BACKGROUND/AIM: The aim of this study was to establish a strategy for high-level
      production of single-chain variable fragment (scFv) antibodies fused with
      interleukin-2 (IL-2) in Escherichia coli. MATERIALS AND METHODS: We constructed
      two fusion sequences consisting of a scFv gene derived from a mouse monoclonal
      antibody against a tumor-associated antigen (MK-1) and human Interleukin-2(IL-2)
      gene, ligated the fusions into pET15b and transformed into three different E.
      coli strains. The effects of temperature, isopropyl-beta-D-thiogalactopyranoside
      (IPTG) concentration and duration of IPTG induction were investigated. RESULTS:
      Employing E. coli strain Rosetta-gami B, which has an oxidizing cytoplasm that
      facilitates cytoplasmic disulfide bond formation, improved the level of soluble
      protein expression. Under optimal conditions, the highest levels of fusion
      protein expression and high percentages of the proteins were found in their
      soluble form. Specifically, 89.29% (0.28 g/l) of one fusion protein was soluble
      after a 10-h induction and 84.61% (0.26 g/l) of the other fusion protein was
      soluble after a separate 10-h induction. When analyzed by enzyme-linked
      immunosorbent assay, the partially-purified fusion proteins retained a specific
      binding activity to the cell lysate of Chinese hamster ovary (CHO) cells
      expressing MK-1. CONCLUSION: Taken together, the methods described herein permit
      the production of substantial amounts of the fusion proteins for conducting
      functional studies on the biological role of these fusion proteins.

PMID- 25075016
TI  - Random migration contributes to cytotoxicity of activated CD8+ T-lymphocytes but
      not NK cells.
AB  - Activated lymphocytes have the ability to undergo non-directional cell movement
      known as random migration, although the biological role for this remains unclear.
      Herein, we investigated how random migration affects cytotoxicity of activated
      lymphocytes using time-lapse imaging analysis. The kinetics of random migration
      paralleled cytotoxicity in activated lymphocytes. Sphingosine-1-phosphate (S1P)
      and its receptor-1 (S1PR1) play an important role in lymphocyte migration.
      Phosphorylated FTY720 (FTYP), a structural analog of S1P, significantly inhibited
      random migration and cytotoxicity of activated CD3(+)NKG2D(+)CD8(+) T-lymphocytes
      but not CD3(-)NKG2D(+)CD56(+) natural killer (NK) cells. In a mouse xenograft
      model, FTYP-treated activated lymphocytes exhibited lower cytotoxicity and less
      tumor infiltration for activated CD3(+)NKG2D(+) T-lymphocytes but not CD3(
      )NKG2D(+) NK cells. These results suggest that random migration contributes to
      the cytotoxicity of activated CD8(+) T-cells but not of NK cells. 

PMID- 25075017
TI  - Prognostic microRNA expression signature from examination of colorectal primary
      and metastatic tumors.
AB  - While previous studies have described associations between specific microRNAs and
      colorectal cancer (CRC) metastasis, our understanding of microRNA regulation of
      metastatic spread remains largely unexplored. To identify microRNAs critical for
      disease progression, we measured microRNA expression in primary CRC tumors and
      synchronous liver metastases in 19 cases using quantitative polymerase chain
      reaction (qPCR) arrays. We identified 16 microRNAs significantly differentially
      expressed between primary tumors and liver metastases that distinguish primary
      tumors and liver metastases by hierarchical clustering. Combinations of microRNAs
      expressed in the primary tumor and in the metastatic tumor are associated with
      survival, but these signatures have no microRNAs in common. We found that
      increased expression of miR-210 and miR-133b in liver metastases compared to
      primary tumors is associated with lower survival. We propose that evaluating the
      change in expression between primary and metastatic tumors in each patient may
      lead to improved biomarker development. 

PMID- 25075018
TI  - Nuclear expression of phosphorylated focal adhesion kinase is associated with
      poor prognosis in human colorectal cancer.
AB  - AIM: To determine whether phosphorylated focal adhesion kinase (P-FAK) has
      prognostic value in colorectal cancer (CRC) and to test whether it has any
      association with Tensin 4 (TNS4) expression. MATERIALS AND METHODS: P-FAK
      expression was assessed using immunohistochemistry in 462 CRC cases arrayed on a
      tissue microarray. P-FAK and TNS4 expression were assessed by
      immunohistochemistry in 40 cases of paired primary colorectal cancer and
      corresponding hepatic metastases. RESULTS: Nuclear P-FAK expression was observed
      in 44% of studied cases. Positive nuclear P-FAK expression was associated with
      shorter disease-specific survival in univariate (p=0.005) and multivariate
      analysis (p=0.016). P-FAK expression was greater in metastases than the primary
      tumours (p<0.001) and showed significant association with nuclear TNS4 (p<0.001)
      in metastases. CONCLUSION: P-FAK expression is an independent prognostic marker
      in CRC. The present data suggest that the FAK signalling pathway may interact
      with TNS4, a known oncogene in CRC.

PMID- 25075019
TI  - Potentiation of natural killer cell activity with myricetin.
AB  - BACKGROUND/AIM: Myricetin is a flavanoid that can be found in a variety of food
      sources, including red wine. Several reports have indicated that flavonoids may
      reduce the disease risk of cancer. The aim of the present study was to
      investigate the effect of some flavonols on natural killer (NK) cell activity.
      MATERIALS AND METHODS: A time-resolved fluorometric assay (TDA-labeled K562
      target cells) was used for measuring the cytotoxic activity of NK-cells pre
      treated with different flavonoids. RESULTS: A limited number of flavanoids was
      tested for their ability to enhance the NK activity. Pre-treating NK cells with
      myricetin, could potentiate their ability to kill K562 erythroleukemia cells.
      This enhancement of the NK activity was observed in a dose-dependent manner.
      Similar treatments with the structurally similar molecule quercetin, that lacks
      one hydroxyl group, did not have any impact at all on NK activity. CONCLUSION:
      The enhanced cytotoxic activity observed with myricetin-pretreated-NK cells might
      shed some light on human studies indicating a preventive role of flavonols
      against cancer.

PMID- 25075020
TI  - Anti-tumor effect of novel cationic biomaterials in prostate cancer.
AB  - BACKGROUND: Tumor cells expressing excessive anionic-charged sialic acid can be
      potentially targeted by cationic polymers which may inhibit tumor growth. In the
      present study, three new families of cationic polymers were synthesized to assess
      their effects on prostate cancer cells. MATERIALS AND METHODS: Cationic polymers
      effects on PC3 prostate cancer cells and normal prostate epithelial cell (RWPE-1)
      were assessed using cell viability, DNA fragmentation, apoptosis assays and
      confocal microscopy. RESULTS: The dextran-based polymer (Dex-PA-3X) (40 MUg/ml)
      and the vinyl-based PolyAETA (5 MUg/ml) induced a significant reduction in cell
      viability in PC3 cells (85% and 50%, respectively; p<0.05) in comparison to RWPE
      1 cells. Furthermore, Dex-PA-3X induced a 50%, and PolyAETA induced a 35%
      increase in cell death in PC3 cells compared to RWPE-1 cells measured by DNA
      fragmentation assay. Lower concentrations of both polymers induced apoptosis
      while higher concentrations induced both apoptosis and necrosis by
      immunostaining. Confocal microscopy indicated the localization of Dex-PA in the
      cytoplasm of PC3 but not RWPE-1 cells, while PolyAETA was seen in both PC3 and
      RWPE-1 cells, but at lower intensity in RWPE-1 cells. CONCLUSION: The newly
      synthesized cationic polymers Dex-PA-3X and PolyAETA selectively bind to, reduce
      viability and induce cell apoptosis in prostate cancer cells, suggesting that
      targeting negatively-charged tumor cells could be a novel strategy to treat
      prostate cancer.

PMID- 25075021
TI  - Extracellular matrix of galectin-1-exposed dermal and tumor-associated
      fibroblasts favors growth of human umbilical vein endothelial cells in vitro: a
      short report.
AB  - BACKGROUND/AIM: Stromal cells in the tumor microenvironment are primarily
      considered as sources of promalignant factors. The objective of our study was to
      define the effect of extracellular matrix (ECM) produced by normal dermal or
      cancer-associated fibroblasts exposed to adhesion/growth-regulatory lectin
      galectin-1 on human umbilical vein endothelial cells (HUVECs). MATERIALS AND
      METHODS: Fibroblasts were cultured for 10 days with lectin, followed by removing
      cellular constituents after an osmotic shock. Freshly-isolated HUVECs were placed
      on the ECM. In parallel, HUVECs were seeded on untreated and gelatin-coated
      surfaces as controls. A positive control for growth of HUVECs culture using
      medium supplemented with vascular endothelial growth factor completed the test
      panel. Cells were kept in contact to the substratum for two days and then
      processed for immunocytochemistry. RESULTS: HUVECs seeded on fibroblast-generated
      ECM presented a comparatively high degree of proliferation. Furthermore, contact
      to substratum produced by tumor-associated fibroblasts led to generation of a
      meshwork especially rich in fibronectin. CONCLUSION: Galectin-1 is apparently
      capable to trigger ECM production favorable for growth of HUVECs, prompting
      further work on characterizing structural features of the ECM and in situ
      correlation of lectin presence, ECM constitution and neoangiogenesis.

PMID- 25075022
TI  - Expression of somatostatin type-2 and -4 receptor and correlation with
      histological type in breast cancer.
AB  - BACKGROUND: Somatostatin is produced by hypothalamic cells and also by tumors. We
      were interested to evaluate the somatostatin type 2 (SSTR2) and type 4 (SSTR4)
      receptor expression on a large sample cohort of breast cancer cases. MATERIALS
      AND METHODS: We used two different Tissue Micro Arrays (TMA) to evaluate SSTR2
      and SSTR4 distribution. We evaluated the correlation between SSTR2 and SSTR4
      expression and 18 tumor cells markers. We also assessed SSTR mRNA expression on
      an independent breast cancer population and correlated levels of SSTR2 and SSTR4
      expression to molecular breast cancer subtypes. RESULTS: 268 tumors were
      analyzed. The tumor overexpression of estrogen receptor was significantly
      correlated to the expression of SSTR2 (p=0.05) and SSTR4 (p=0.04). On principal
      component analysis, SSTR2 subtype characterized the luminal tumor type. On an
      independent breast cancer population, expression of SSTR2 and SSTR4 are
      independent from Human Epidermal Growth Factor Receptor 2 (Her2) and correlated
      with luminal tumors. CONCLUSION: Expression of somatostatin receptors is a marker
      of luminal breast tumors.

PMID- 25075023
TI  - Histological groups of human postpubertal testicular germ cell tumours harbour
      different genetic alterations.
AB  - BACKGROUND: Testicular germ cell tumours are the most common malignancies in
      young males. Molecular biology studies of these tumours are often contradictory.
      Two histological groups, seminoma and non-seminoma, differ both morphologically
      and in malignant behaviour. Although a common cytogenetic feature is seen, namely
      the amplification of the 12p chromosomal region, the development mechanisms of
      less aggressive seminomas and more aggressive non-seminomas are unknown.
      MATERIALS AND METHODS: Occurrence of structural genetic alterations was analyzed
      in 18 seminomas and 22 non-seminomas for genes involved in the malignant tumour
      phenotype: cadherin 1, Type 1, E-cadherin (Epithelial), CDH1; adenomatous
      polyposis coli, APC; NME/NM23 nucleoside diphosphate kinase 1, NME1; tumour
      protein P53, TP53; cyclin-dependent kinase inhibitor 2A, CDKN2A; retinoblastoma
      1, RB1; RAD51 recombinase, RAD51; mutS homolog 2, MSH2; MutL homolog 1, MLH1;
      breast cancer 1, early onset, BRCA1; BCL2-Associated X Protein, BAX; ATP-Binding
      Cassette, Sub-Family G (WHITE), Member 2, ABCG2. Genetic alterations, loss of
      heterozygosity and microsatellite instability, were analyzed using restriction
      fragment or microsatellite repeat length polymorphisms. RESULTS: A difference in
      genetic alteration occurrence between seminomas and non-seminomas was observed.
      CONCLUSION: Occurrence of genetic alterations correlates with clinical behaviour
      of these tumours and may indicate that such alterations could occur early in the
      development of seminomas and non-seminomas.

PMID- 25075024
TI  - Novel piperazinediones as antitumor agents.
AB  - Chemical modification of dipeptide mimetic azatyrosine led to a series of
      piperazinediones. Thirteen piperazinediones were synthesized and tested for their
      anticancer activity. This series of piperazinedione compounds exhibited potent
      anticancer activities against human disease-oriented cancer cell lines in NCI60
      cancer screening (National Cancer Institute, USA). Among them, four leads
      (compound 10: , 18: , 21: , and 22: ) exhibited in vitro tumor growth
      suppression, reducing tumor cell growth to 45.7%- 56.3%, and exhibited broad
      spectrum activities. Compound 18: , with 50% cancer cell growth inhibition (GI50)
      <10 nM in 45 cell lines from the NCI, was selected as the lead for further
      mechanism of action studies. The mechanism of action was predicted by the COMPARE
      algorithm and confirmed by experiments as inhibition of tubulin polymerization
      which inhibits the formation of microtubules. 

PMID- 25075025
TI  - Activation of the leukemia plasmacytoid dendritic cell line PMDC05 by Toho-1, a
      novel IDO inhibitor.
AB  - BACKGROUND/AIM: Indoleamine-2,3-dioxygenase (IDO) is a rate-limiting enzyme for
      tryptophan metabolism and plays an immunosuppressive role. Antigen-presenting
      cells, when activated, increase the expression of IDO, which results in the
      suppression of subsequent immune reaction. A novel IDO inhibitor, Toho-1, was
      explored for its applicability to immunotherapy. MATERIALS AND METHODS: We
      investigated the effects of Toho-1 on antigen presentation and antigen-specific
      cytotoxic T-lymphocyte-inducing ability of leukemia plasmacytoid dendritic cell
      line PMDC05, which was established in our laboratory. RESULTS: While antigen
      presentation-associated molecules in PMDC05 cells were increased by stimulation
      with lipopolysaccharide and interferon-gamma, IDO mRNA and protein expression
      were also enhanced. Such treatment of PMDC05 cells in combination with Toho-1
      enhanced the antigen-presenting and CTL-inducing ability of PMDC05 cells.
      CONCLUSION: These findings suggest the ability of Toho-1 to potentiate antigen
      presenting cells and its applicability in immunotherapy of cancer.

PMID- 25075026
TI  - SOX18 expression predicts response to platinum-based chemotherapy in ovarian
      cancer.
AB  - BACKGROUND: SOX18 is a transcription factor known to be involved in blood and
      lymphatic vessel, hair follicle development, and wound healing processes. In
      addition, it has been reported that SOX18 may influence cancer growth. The role
      of SOX18 expression in ovarian cancer (OC) has not been determined. MATERIALS AND
      METHODS: SOX18 expression was assessed in 85 OC cases using immunohistochemical
      methods and in ovarian cancer cell lines on the mRNA and protein level. RESULTS:
      SOX18 was expressed in cancer cell nuclei as well as the cytoplasm. Higher
      nuclear SOX18 expression was associated with presence of residual disease
      following surgical treatment (p=0.0158) and advanced disease stage (p=0.0056).
      Univariate survival analysis revealed that high SOX18 (p=0.0125) expression,
      presence of residual disease (p<0.0001) and advanced disease stage (p<0.0324)
      predicted poor patient outcome. CONCLUSION: SOX18 may be a new predictive marker
      for OC.

PMID- 25075027
TI  - Dehydroepiandrosterone inhibits proliferation and suppresses migration of human
      cervical cancer cell lines.
AB  - Dehydroepiandrosterone (DHEA), an adrenal steroid which is most abundant in human
      plasma, has a protective role against several types of cancer; however, its
      mechanisms of action are unknown. We evaluated the effect of DHEA on the
      proliferation and migration of three cell lines derived from cervical cancer.
      Cell proliferation was evaluated by crystal violet staining; migration by
      attachment, transwell and wound assays. DHEA inhibited the proliferation of InBl
      and SiHa cells, with a half-maximal inhibitory concentration (IC50) of 30 MUM,
      whereas the proliferation of HeLa cells was inhibited with an IC50 of 70 MUM.
      DHEA at these IC50 inhibited attachment of cells to the plastic surface of the
      culture wells, and migration, was evaluated using transwells after 24 h of
      exposure. DHEA also reduced migration of the three cell lines into the wound
      area. These results suggest that a possible mechanism of DHEA in protecting
      against cervical cancer is the inhibition of proliferation and migration of tumor
      cells. DHEA could be useful in the prevention or treatment of cervical cancer. 

PMID- 25075028
TI  - A tertiary sulfonium compound, dimethylsulfoniopropionate in green sea algae,
      completely suppresses crucial Ehrlich ascites carcinoma in mice.
AB  - BACKGROUND/AIM: Dimethylsulfoniopropionate (DMSP) has been intensively studied in
      bacteria, plankton, algae and salt-resistant plants to investigate its metabolism
      and fate in the atmosphere. However, its effects on diseased terrestrial animals
      have not yet been examined. We have found that DMSP exerts a great healing effect
      for a variety of inflammatory disorders in rodents. In the present study, effects
      of single and high concentration of DMSP on terrible Ehrlich ascites carcinoma
      (EAC) bearing-mice with unavoidable-rapid death were examined. RESULTS: We found
      that high concentration of DMSP completely suppresses acute EAC, which has never
      been eradicated, and accumulates large amounts of activated macrophages with no
      inflammation on various viscera in the peritoneal cavity of normal mice.
      CONCLUSION: These results show that DMSP is a new and potent anticancer compound
      with no side-effects, most likely playing a vital role for cancer immune therapy.

PMID- 25075029
TI  - Can expression of CXCL12 and CXCR4 be used to predict survival of gastric cancer
      patients?
AB  - BACKGROUND: Currently, there is no effective therapy for advanced gastric cancer.
      In this study, we investigated whether protein expression of CXCL12 and/or its
      receptor CXCR4 is associated with clinicopathological features and/or survival of
      gastric cancer. MATERIALS AND METHODS: Primary tumor specimens from patients
      (n=137) with pathologically-confirmed gastric cancer, collected between 2001 and
      2009, were analyzed by immunohistochemistry using anti-CXCL12 and anti-CXCR4
      antibodies. RESULTS: Expression of CXCL12 was directly associated with tumor
      differentiation (p=0.0143) but inversely associated with depth of invasion
      (p=0.0255), lymphatic invasion (p=0.0173), venous invasion (p=0.0022) and stage
      (p=0.049). Expression of CXCR4 was associated with depth of invasion (p=0.005)
      and stage (p=0.028). Increased CXCR4 expression, but not CXCL12 expression, was
      associated with 5-year cancer-specific survival (p=0.0079). CONCLUSION: CXCL12
      was not associated with survival. Positive CXCR4 expression in gastric carcinoma
      was significantly associated with poor survival and, therefore, may be a
      potential biomarker for predicting poor survival.

PMID- 25075031
TI  - Silencing of phosphoinositide-specific phospholipase C epsilon remodulates the
      expression of the phosphoinositide signal transduction pathway in human
      osteosarcoma cell lines.
AB  - BACKGROUND: Ezrin, a member of the ezrin-radixin-moesin family, is involved in
      the metastatic spread of osteosarcoma. Ezrin binds phosphatydil inositol-4,5
      bisphosphate (PIP2), a crucial molecule of the phosphoinositide signal
      transduction pathway. PIP2 levels are regulated by phosphoinositide-specific
      phospholipase C (PI-PLC) enzymes. PI-PLCepsilon isoform, a well-characterized
      direct effector of rat sarcoma (RAS), is at a unique convergence point for the
      broad range of signaling pathways that promote RAS GTPase-mediated signalling.
      MATERIALS AND METHODS: By using molecular biology methods and microscopic
      analyses, we analyzed the expression of ezrin and PLC genes after silencing of
      PLCE (OMIM *608414) in 143B and Hs888 cell lines. RESULTS: The growth rate of the
      cells was slowed, and the expression of ezrin, PLCB1, PLCG2 and PLCD4 was
      significantly modified. Ezrin displacement from the plasma membrane was observed.
      CONCLUSION: The present results corroborate the hypothesis that ezrin and the PI
      signal transduction system are involved in a common network.

PMID- 25075030
TI  - Expression of Nogo isoforms and Nogo-B receptor (NgBR) in non-small cell lung
      carcinomas.
AB  - BACKGROUND: Nogo-B was recently shown to be involved in proliferation, apoptosis
      and invasiveness of cancer cells, whereas its specific receptor (NgBR) was found
      to be up-regulated in estrogen receptor-alpha positive breast cancer. No data are
      currently available concerning their expression in non-small cell lung carcinomas
      (NSCLC). MATERIALS AND METHODS: Expression of Nogo isoforms and NgBR was studied
      in 191 NSCLC. RESULTS: Higher Nogo-A/B immunoreactivity was noted in cancer cells
      of squamous cell carcinomas (SQC) compared to adenocarcinomas (p<0.001). Stage II
      IV tumors had the lowest Nogo-A/B expression (p<0.0001) compared to stage I
      cases. Nogo-A/B expression decreased with increasing SQC malignancy grade
      (p=0.026). Significant NgBR mRNA down-regulation was associated with larger
      primary tumor size (p=0.039), lymph node involvement (p=0.039) and advancement
      stage (p=0.0054). Low NgBR mRNA expression predicted poor patients outcome
      (p=0.029). CONCLUSION: The current data may point to the involvement of Nogo
      isoforms and NgBR in the pathogenesis of NSCLC.

PMID- 25075032
TI  - Evaluating the cytotoxic effects of novel quinone compounds.
AB  - BACKGROUND/AIM: Quinone-containing compounds can induce cell death in cancer
      cells and are, therefore, promising lead compounds for the development of novel
      anti-cancer drugs. MATERIALS AND METHODS: In the present study, we evaluated the
      cytotoxic effects of fifteen novel synthetic quinone-containing compounds in cell
      cultures in an attempt to establish structure/activity relationships for these
      compounds. The compounds were clustered into four groups (1, 2, 3, 4) based on
      common structural features. In vitro cell cultures were treated for 24 h with the
      compounds, after which cell viability was assessed by flow cytometry. The
      APOPercentageTM assay, the Terminal deoxynucleotidyl transferase mediated dUTP
      Nick End Labeling (TUNEL) assay and the caspase-3 assay was used to investigate
      the activation of apoptosis in the cells. RESULTS: Compounds from groups 2 and 4
      were highly toxic to the cells. The compounds induced apoptosis in some human
      cancer cell cultures and exhibited low toxicity towards the non-cancerous cell
      line, KMST-6. The induction of apoptosis in CHO cells was associated with the
      activation of caspase-3 cleavage, DNA fragmentation and the reactive oxygen
      species (ROS) generation. CONCLUSION: The present study demonstrates that five of
      the quinone-containing compounds induced apoptosis in human cancer cells and are
      therefore promising lead compounds for the development of novel anticancer drugs.

PMID- 25075033
TI  - Anticancer activity of hispidin via reactive oxygen species-mediated apoptosis in
      colon cancer cells.
AB  - Few studies have been performed on the anticancer activity of hispidin, a
      phenolic compound produced from the medicinal mushroom Phellinus linteus. Herein,
      we studied hispidin-induced apoptosis, which is associated with the generation of
      reactive oxygen species (ROS) in colon cancer cells. Hispidin was found to reduce
      cell viability both in mouse and human colon cancer cells. Apoptotic cell
      morphological changes were observed by microscopy, and apoptosis was assessed in
      hispidin-treated cells using a biochemical method. The results showed
      accumulation of the sub-G1 cell population and increase in early apoptosis in a
      dose-dependent manner. In addition, hispidin induced apoptosis through up
      regulation of both intrinsic and extrinsic apoptotic pathways. Although the
      molecular mechanism underlying hispidin-induced apoptosis is known to involve the
      generation of ROS, however hispidin did not show any apoptosis in the pre
      treatment with a ROS scavenger, N-acetyl-L-cysteine. In conclusion, hispidin
      induces both intrinsic and extrinsic apoptotic pathways mediated by ROS in colon
      cancer cells, thereby suggesting that hispidin could be a promising new
      anticancer agent. 

PMID- 25075034
TI  - High oxygen partial pressure increases photodynamic effect on HeLa cell lines in
      the presence of chloraluminium phthalocyanine.
AB  - BACKGROUND: Photodynamic therapy (PDT) is linked with oxidative damage of
      biomolecules causing significant impairment of essential cellular functions that
      lead to cell death. It is the reason why photodynamic therapy has found
      application in treatment of different oncological, cardiovascular, skin and eye
      diseases. Efficacy of PDT depends on combined action of three components;
      sensitizer, light and oxygen. In the present study, we examined whether higher
      partial pressure of oxygen increases lethality in HeLa cell lines exposed to
      light in the presence of chloraluminium phthalocyanine disulfonate (ClAlPcS2).
      METHODS: ClAlPcS2- sensitized HeLa cells incubated under different oxygen
      conditions were exposed to PDT. Production of singlet oxygen ((1)O2) and other
      forms of reactive oxygen species (ROS) as well as changes in mitochondrial
      membrane potential were determined by appropriately sensitive fluorescence
      probes. The effect of PDT on HeLa cell viability under different oxygen
      conditions was quantified using the standard methylthiazol tetrazolium (MTT)
      test. RESULTS: At the highest oxygen concentration of 28 +/- 2 mg/l HeLa cells
      were significantly more sensitive to light-activated ClAlPcS2 (EC50=0.29 +/- 0.05
      MUM) in comparison to cells incubated at lower oxygen concentrations of 8 +/- 0.5
      and 0.5 +/- 0.1 mg/l, where the half maximal effective concentration was 0.42 +/-
      0.06 MUM and 0.94 +/- 0.14 MUM, respectively. Moreover, we found that the higher
      presence of oxygen is accompanied with higher production of singlet oxygen, a
      higher rate of type II photodynamic reactions, and a significant drop in the
      mitochondrial membrane potential. CONCLUSION: These results demonstrate that the
      photodynamic effect in cervical cancer cells utilizing ClAlPcS2 significantly
      depends on oxygen level.

PMID- 25075036
TI  - Evaluation of the contribution of methylenetetrahydrofolate reductase genotypes
      to Taiwan breast cancer.
AB  - The aim of the present study was to evaluate the effects of the genotypic
      polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and its interaction
      with early-onset breast cancer risk in Taiwan. Two well-known polymorphic
      variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed and
      their joint effects with individual age- and estrogen-related factors on breast
      cancer risk were discussed. In total, 1,232 patients with breast cancer and 1,232
      healthy controls were genotyped by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). The MTHFR C677T genotype, but not the A1298C, was
      differently distributed between cancer and control groups. The T allele of MTHFR
      C677T was significantly more frequently found in controls than in patients with
      cancer. In addition, females carrying MTHFR C677T CT or TT genotypes had a higher
      odds ratio of 1.21 (95% confidence interval=1.03-1.42, p=1.85E-5) for breast
      cancer, especially before the age of 45.4 years (odds ratio=1.51 and 95%
      confidence interval=1.20-1.90). Our results indicate that MTHFR C677T T allele
      was associated with increased risk of breast cancer in Taiwan, especially in
      cases who were 45.4 old or younger and with earlier menarche age (<12.2 years). 

PMID- 25075035
TI  - Targeting the Wnt/beta-catenin pathway in renal cell carcinoma.
AB  - BACKGROUND/AIM: Advanced renal cancer still has a very poor prognosis. In this
      regard recent investigations demonstrated a constitutive activation of the Wnt
      signaling pathway in renal cell carcinoma (RCC) thereby promoting an exaggerated
      cell proliferation. Especially, beta-catenin overactivation and the functional
      loss of endogenous Wnt antagonists are associated with RCC carcinogenesis and
      progression. Thus, influencing Wnt signaling might represent a promising target
      in RCC treatment. MATERIALS AND METHODS: It was recently confirmed that
      ethacrynic acid (EA), ciclopirox olamine (CIC) and piroctone olamine (PO) can
      inhibit Wnt signaling in various cancer cell lines. Herein we investigated their
      cytotoxic potential towards human RCC cells and their influence on the Wnt
      pathway concerning apoptosis as determined by 3,3'-dihexyloxacarbocyanine iodide
      (DiOC6) and propidium iodide (PI) staining in flow cytometry and immunoblotting.
      RESULTS: All three agents, EA, CIC and PO triggered a significant apoptotic
      activity in tested RCC cell lines in a time- and concentration-dependent manner.
      Moreover, exposure to CIC and PO decreased the expression of beta-catenin as the
      pivotal feature within the canonical Wnt pathway. However, beta-catenin
      expression increased upon the treatment with EA. CONCLUSION: These results reveal
      a significant selective induction of apoptosis by EA, CIC and PO and suggest a
      suppression of RCC survival in part due to inhibition of Wnt/beta-catenin
      signaling. The development of targeted-therapies affecting the Wnt signaling
      pathway might therefore lead to novel treatment options for RCC patients.

PMID- 25075037
TI  - Search of new cytotoxic crude materials against human oral squamous cell
      carcinoma using 1H NMR-based metabolomics.
AB  - BACKGROUND: The 5-year survival rate of the oral cancer patients has remained at
      approximately the 50% level during the past 30 years, possibly due to the poor
      tumor-selectivity of conventional anticancer drugs. This prompted us to search
      new plant extracts that have higher cytotoxicity against cancer cells than normal
      cells. MATERIALS AND METHODS: Two human oral squamous cell carcinoma cell lines
      (HSC-2 and HSC-4) and two normal oral cells (gingival and periodontal ligament
      fibroblasts; HGF and HPLF) were incubated for 48 h with various concentrations of
      crude plant extract and the viable cell number was determined by the (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The 50%
      cytotoxic concentration (CC50) was determined from the dose-response curve. Tumor
      specificity (TS) was determined by the following equation: TS=mean CC50 (normal
      cells)/mean CC50 (cancer cell lines). Metabolic profiling techniques based on
      (1)H nuclear magnetic resonance (NMR) were applied to gain the chemical
      structural insight for cytotoxicity induction. RESULTS: Among 24 plant extracts,
      Camptotheca acuminate leaf, a well-known source for camptothecin, showed the
      highest TS value (88.3), followed by Vitis s.p.p. (>3.5), Sasa veitchii (>2.3)
      and Phellodendron amurense (>2.1), whereas other plant extracts showed much lower
      TS value (<2). These cytotoxic extracts made cluster on principal component
      analysis (PCA) score plot. CONCLUSION: The TS value determined by the present
      method seems to reflect the anti-tumor potential of each plant extract, while a
      part of the cytotoxic compounds present in these extracts may have common
      chemical structures.

PMID- 25075038
TI  - Serum vimentin methylation as a potential marker for colorectal cancer.
AB  - AIMS: The present study aimed to examine the feasibility of detecting vimentin
      (VIM) methylation in the serum of patients with colorectal cancer (CRC) and to
      determine the effectiveness of a relatively simple, inexpensive, and non-invasive
      test performed in combination with the conventional carcinoembryonic antigen
      analysis. MATERIALS AND METHODS: VIM methylation in the serum DNA of 242 patients
      with CRC was measured by a quantitative methylation-specific polymerase chain
      reaction. RESULTS: A significantly higher positive rate was obtained for VIM
      methylation than for carcinoembryonic antigen or carbohydrate antigen 19-9 in
      stage 0, I, and II patients. The combination of all three markers yielded similar
      sensitivity for patients with disease of stage 0: 57.1%, I: 36.1%, II: 45.2%, and
      III: 55.4%, whereas the sensitivity reached 85.7% for patients with stage IV
      disease. CONCLUSION: VIM methylation of serum DNA may be a useful marker for the
      early detection of CRC.

PMID- 25075039
TI  - Metformin inhibits tumor cell migration via down-regulation of MMP9 in tamoxifen
      resistant breast cancer cells.
AB  - Metformin is the most widely used anti-diabetic drug in the world. Recent
      evidence indicates that metformin could potentially inhibit tumorigenesis. In the
      present study, we found that metformin inhibited cell migration and invasion of
      phorbol 12-myristate 13-acetate-induced MCF-7 and tamoxifen-resistant MCF-7
      breast cancer cells. This inhibition was correlated with the modulation of matrix
      metalloproteinase-9 (MMP9) via the suppression of its expression and proteolytic
      activity. These results indicate that metformin leads to the suppression of
      migration and invasion through regulation of MMP9 and it may have potential as an
      anticancer drug for therapy in human breast cancer, especially of chemoresistant
      cancer cells. 

PMID- 25075040
TI  - Semi-synthesis of nitrogen derivatives of oleanolic acid and effect on breast
      carcinoma MCF-7 cells.
AB  - BACKGROUND: Oleanolic acid is a triterpenoid that has shown in vitro cytotoxic
      activity against human tumour cells and is known to be present in many higher
      plants. MATERIALS AND METHODS: Oleanolic acid is known to have some biological
      potential including anticancer property. Oleanolic acid was isolated from the
      ethyl acetate fraction of Syzygium aromaticum seed with an aim of dervitatising
      the functional group and evaluating the biological activities of the semi
      synthesised compounds. Acylation of the alcohol functional group of the oleanolic
      acid afforded the opportunity of hydrazine reaction to give 3-acetoleanolic
      hydrazide. Further reaction of 3-acetoleanolic hydrazide with benzyladehyde,
      glacial acetic acid and methanol resulted in the synthesis of the corresponding 3
      acetoxyoleanolic hydrazone. RESULTS: The semi-synthetic oleanolic acid
      derivatives did not exhibit enhanced cytotoxic activity over oleanolic acid
      itself. CONCLUSION: 3-acetoxyoleanolic hydrazide has a potent anticancer
      activity.

PMID- 25075041
TI  - Mechanisms of action of 17betaH-neriifolin on its anticancer effect in SKOV-3
      ovarian cancer cell line.
AB  - AIM: Abnormalities in apoptotic signalling pathways often occur in cancer cells
      and limit the successful chemotherapy outcomes in cancers. Therefore, there is an
      urgent need to discover new anticancer agents with novel mechanisms of action to
      overcome the resistance effect in chemotherapy. MATERIALS AND METHODS: In the
      present study, the anticancer effects and the mechanisms of action of 17betaH
      neriifolin (cardiac glycoside) were evaluated by terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) assay and a proteomic approach in
      treated and non-treated SKOV-3 ovarian cancer cells. RESULTS: 17betaH-neriifolin
      was found to be active with IC50 values of 0.01 +/- 0.001 in SKOV-3 ovarian
      cancer cell line, as evaluated by the sulforhodamine B (SRB) assay. RESULTS from
      TUNEL assay indicated that 17betaH-neriifolin caused apoptosis in SKOV-3 cells in
      a dose-dependent manner. Based on differential analysis of treated and non
      treated SKOV-3 two-dimensional electrophoresis (2-DE) profiles, four proteins,
      namely vimentin (VIM), pyruvate kinase, muscle (PKM), heterogeneous nuclear
      ribonucleoprotein A1 (HNRNPA1) and transgelin (TAGLN1) were identified to be
      involved in apoptosis. Other proteins including piggybac transposable element
      derived 5 (PGBD5), DENN/MADD domain containing 2D (DENND2D) and formin-like
      1(FMNL) have also been identified to be associated in SKOV-3 cell death induced
      by 17betaH-neriifolin. CONCLUSION: These findings may provide new insights on the
      potential of 17betaH-neriifolin's mechanism of action in killing ovarian cancer
      cells.

PMID- 25075042
TI  - Comparative analysis of Hsp10 and Hsp90 expression in healthy mucosa and
      adenocarcinoma of the large bowel.
AB  - BACKGROUND: Heat shock proteins (Hsps) assist other proteins in their folding and
      drive the degradation of defective proteins. During evolution, these proteins
      have also acquired other roles. Hsp10 is involved in immunomodulation and tumor
      progression. Hsp90 stabilizes a range of "client" proteins involved in cell
      signaling. The present study evaluated the expression levels of Hsp10 and Hsp90
      in normal mucosa and adenocarcinoma samples of human large bowel. MATERIALS AND
      METHODS: Samples of normal mucosa and adenocarcinoma were collected and Reverse
      transcriptase-polymerase chain reaction RT-PCR, western blotting (WB) analyses,
      as well as immunohistochemistry were performed to evaluate the expression levels
      of Hsp10 and Hsp90. RESULTS: RT-PCR showed a higher gene expression of Hsp10 and
      Hsp90 in adenocarcinoma samples compared to healthy mucosa. WB results confirmed
      these findings. Immunohistochemistry revealed higher levels of Hsp10 in
      adenocarcinoma in both the epithelium and the lamina propria, while Hsp90
      expression was higher in the adenocarcinoma samples only in the lamina propria.
      CONCLUSION: Hsp10 and Hsp90 may be involved in large bowel carcinogenesis.

PMID- 25075043
TI  - alpha-Phellandrene alters expression of genes associated with DNA damage, cell
      cycle, and apoptosis in murine leukemia WEHI-3 cells.
AB  - alpha-phellandrene (alpha-PA) is a cyclic monoterpene, present in natural plants
      such as Schinus molle L. alpha-PA promotes immune responses in mice in vivo.
      However, there is no available information on whether alpha-PA affects gene
      expression in leukemia cells. The present study determined effects of alpha-PA on
      expression levels of genes associated with DNA damage, cell cycle and apoptotic
      cell death in mouse leukemia WEHI-3 cells. WEHI-3 cells were treated with 10 MUM
      alpha-PA for 24 h, cells were harvested and total RNA was extracted, and gene
      expression was analyzed by cDNA microarray. Results indicated that alpha-PA up
      regulated 10 genes 4-fold, 13 by over 3-fold and 175 by over 2-fold; 21 genes
      were down-regulated by over 4-fold, 26 genes by over 3-fold and expression of 204
      genes was altered by at leas 2-fold compared with the untreated control cells.
      DNA damage-associated genes such as DNA damage-inducer transcript 4 and DNA
      fragmentation factor were up-regulated by 4-fold and over 2-fold, respectively;
      cell-cycle check point genes such as cyclin G2 and cyclin-dependent kinases
      inhibitor 2D and IA (p21) were up-regulated by over 3-fold and over 2-fold,
      respectively; apoptosis-associated genes such as BCL2/adenovirus EIB interacting
      protein 3, XIAP-associated factor 1, BCL2 modifying factor, caspase-8 and FADD
      like apoptosis regulator were over 2-fold up-regulated. Furthermore, DNA damage
      associated gene TATA box binding protein was over 4-fold down-regulated, and
      D19Ertd652c (DNA segment) over 2-fold down-regulated; cell cycle-associated gene
      cyclin E2 was over 2-fold down-regulated; apoptosis associated gene growth arrest
      specific 5 was over 9-fold down-regulated, Gm5426 (ATP synthase) was over 3-fold
      down-regulated, and death box polypeptide 33 was over 2-fold down-regulated.
      Based on these observations, alpha-PA altered gene expression in WEHI-3 cells in
      vitro. 

PMID- 25075044
TI  - Claudins as prognostic factors for renal cell cancer.
AB  - BACKGROUND: Claudins are tight junction proteins and their expression is often
      different in normal and corresponding tumor cells. In the present study, we
      determined how the expression of claudins 1-5 and 7 correlated to survival, grade
      and stage of patients with renal cell cancer (RCC). PATIENTS AND METHODS: Primary
      tumor samples were collected retrospectively from 229 RCC patients. Claudins were
      detected by immunohistochemistry using commercial monoclonal antibodies against
      claudins 1-5 and 7. Median survival time was 6.5 years confidence interval (CI)
      (4.5-8.5, n=224). Kaplan-Meier survival estimated method was used in survival
      analyses. RESULTS: Positive expression was detected in 62%, 67%, 45%, 55%, 7% and
      35% of cases for claudins 1, 2, 3, 4, 5 and 7, respectively. High expression of
      claudin 2 was observed in 20% of cases while high expression of other claudins
      was less frequent. Claudins were compared to classical prognostic factors. On
      cross-tabulation, claudin 1 (p<0.001) and claudin 2 (p=0.009) were significantly
      associated with lower-grade and higher-grade tumors, respectively. None of the
      claudins was significantly associated with tumor stage or patient survival.
      CONCLUSION: Claudins 1 and 2 were associated with tumor grade. However, none of
      the claudins was a more powerful prognostic factor than tumor stage.

PMID- 25075045
TI  - Dose-escalated radiation therapy with and without short-course androgen
      deprivation for intermediate-risk prostate cancer.
AB  - AIM: To investigate outcomes in intermediate-risk (IR) prostate cancer patients
      receiving dose-escalated external beam radiation therapy (RT) with or without
      short-course androgen deprivation (ADT). PATIENTS AND METHODS: This study
      comprised of 203 patients with IR prostate cancer who were treated at a single
      institution to a dose of 7,560 cGy or more between 2003-2010. Of these, 62
      (30.5%) patients received ADT. Biochemical recurrence, distant metastatic-free
      survival, prostate cancer-specific survival, and overall survival were analyzed
      using the Kaplan-Meier method. RESULTS: The median follow-up was 62 months and
      the median duration of ADT was 6 months. The 6-year biochemical control was 89.2%
      for those receiving RT plus ADT versus 76.7% in those receiving RT alone
      (p=0.02). There were no differences between the two groups regarding distant
      metastatic-free survival, prostate cancer-specific survival, and overall survival
      (respective p-values of 0.91, 0.50, 0.67). CONCLUSION: Dose-escalated RT and
      short-course ADT results in improved biochemical outcomes for IR prostate cancer.

PMID- 25075046
TI  - Effects of chemoradiotherapy on lymph nodes in patients with rectal
      adenocarcinoma: evaluation of numbers and sizes of retrieved lymph nodes inside
      and outside the radiation field.
AB  - BACKGROUND: Preoperative chemoradiotherapy (CRT) decreases the number of
      retrieved lymph nodes (LNs) in rectal cancer. LNs inside the irradiation field
      are affected by CRT, whereas those outside the irradiation field are affected
      only by concurrent chemotherapy. PATIENTS AND METHODS: The study cohort comprised
      of 210 patients with clinical stage II/III rectal adenocarcinoma. One hundred and
      eight received surgery alone (S group), and 102 received preoperative CRT (40 or
      45 Gy) with concurrent oral UFT or S-1 uracil/tegafur or S-1 (CRT group).
      RESULTS: The number of LNs inside the irradiation field was significantly smaller
      in the CRT group (4 +/- 4) than in the S group (6 +/- 6, p<0.01), but the number
      of LNs outside the irradiation field did not differ (5 +/- 4 in both groups). The
      longest diameters of LNs in the S group were significantly smaller than those of
      the CRT group both inside and outside the irradiation fields (p<0.01).
      CONCLUSION: The effects of CRT on LNs in patients with rectal adenocarcinoma
      differed inside and outside the radiation field.

PMID- 25075047
TI  - Predictive biomarkers for the outcome of vaccination of five therapeutic epitope
      peptides for colorectal cancer.
AB  - BACKGROUND: We previously reported a phase I study of a cancer vaccine using five
      novel HLA-A*2402-restricted peptides, and demonstrated the safety and the
      promising potential of our five-peptide cocktail for advanced colorectal cancer.
      The objective of this analysis was to investigate predictive biomarkers for the
      prior selection of patients who are likely to have clinical benefit from such
      therapy. PATIENTS AND METHODS: Seventeen patients with colorectal cancer who were
      treated with the five peptides underwent a complete blood count, serum chemistry
      tests and enzyme-linked ImmunoSpot assay before the treatment as predictive
      markers of high reactivity to the peptides. RESULTS: Interleukin-6 level was a
      significant predictor for overall survival of patients treated with the peptide
      cocktail (p=0.017). A high neutrophil/lymphocyte ratio was likely to have some
      association with the poor induction of peptide-specific immune reaction.
      CONCLUSION: Interleukin-6 level might be a good predictive biomarker for clinical
      benefit of patients treated with this peptide vaccine.

PMID- 25075048
TI  - Significance of accurate human epidermal growth factor receptor-2 (HER2)
      evaluation as a new biomarker in gastric cancer.
AB  - BACKGROUND: HER2 testing in gastric cancer differs from testing in breast cancer
      because of inherent differences in tumor biology; gastric cancer more frequently
      shows HER2 heterogeneity and incomplete membrane staining. The aim of the present
      study was to evaluate the frequency and accuracy of detection of HER2 expression
      by application of standard criteria in Japanese patients with gastric cancer.
      MATERIAL AND METHODS: A total of 198 tumor specimens were assessed for HER2
      expression by immunohistochemistry (IHC) using the antibodies HercepTestTM and
      4B5. Both hand-operated and automated IHC were performed. RESULTS: HER2
      expression differed according to the IHC method and antibodies used. HER2 IHC3+
      tumors were identified in 21 (10%) and 7 (3.5%) cases by hand-operated and
      automated IHC, respectively. CONCLUSION: Among patients with gastric cancer, FISH
      may be performed in cases of IHC1+ by automated IHC. Further research is required
      to clarify the relevance of HER2 staining and scoring for the clinical response
      to HER2-targeted therapy.

PMID- 25075049
TI  - Management of peripheral neuropathy induced by nab-paclitaxel treatment for
      breast cancer.
AB  - Nanoparticle albumin-bound paclitaxel (nab-PTX) is a key drug used in breast
      cancer treatment which often causes chemotherapy-induced peripheral neuropathy
      (CIPN). No effective approach for CIPN control has been established to date. This
      study assessed a new approach to CIPN integrating two concepts: compression
      therapy using stockings and sleeves, and medication therapy using selected
      prophylactic drugs, including goshajinkigan, which we named the "3S" approach.
      Fourteen breast cancer patients were divided into a 3S group (n=7) and a control
      group (n=7), and were treated with 260 mg/m(2) of nab-PTX once every three weeks.
      CIPN initially developed in five control-group patients and one 3S-group patient
      (p=0.03). Across all cycles, the CIPN grades, as determined by the Common
      Terminology Criteria for Adverse Events (CTCAE), were significantly lower in the
      3S group than in the control group (p<0.001). The mean nab-PTX dose in the 3S
      group was 77.1 mg/m(2)/week versus 64.7 mg/m(2)/week in the control group
      (p<0.01). By controlling the development and severity of CIPN, 3S treatment
      appears to support the use of the recommended nab-PTX dosing for breast cancer
      patients. 

PMID- 25075050
TI  - Expression of Stathmin1 in gastric adenocarcinoma.
AB  - BACKGROUND: Over expression of Stathmin1 (STMN1), activation-induced cytidine
      deaminase (AID) and protein kinase C iota (PKCi) proteins participate in the
      regulation of carcinogenesis. In the present study, we investigated the
      expression of STMN1 in patients with gastric adenocarcinoma and also determined
      the correlation of STMN1 with AID and PKCi proteins. MATERIALS AND METHODS: This
      study was conducted in the Tokushima University Hospital between September 2009
      and September 2010 on a total of 59 patients with gastric adenocarcinoma.
      Stathmin1, AID and PKCi protein expressions were evaluated by immuno
      histochemistry in gastric adenocarcinoma. RESULTS: A strong expression of STMN1
      was significantly associated with gender- and poorly differentiated gastric
      adenocarcinoma (p<0.05). A high mRNA level of STMN1 was found in the tumor tissue
      of gastric adenocarcinoma compared to non-tumor tissue (p<0.05). In addition,
      STMN1 expression was significantly correlated with AID and PKCi protein
      expressions in gastric adenocarcinoma (p<0.05). CONCLUSION: High mRNA level of
      the Stathmin1 gene was significantly expressed in gastric tumor tissue than non
      tumor and strong expression of STMN1 protein is correlated with poorly
      differentiated gastric adenocarcinoma.

PMID- 25075051
TI  - Prognostic nutritional index is associated with survival after total gastrectomy
      for patients with gastric cancer.
AB  - AIM: To investigate the influence of clinical characteristics including
      nutritional markers on postoperative survival in patients undergoing total
      gastrectomy (TG) for gastric cancer (GC). PATIENTS AND METHODS: One hundred fifty
      four patients were enrolled. Uni- and multivariate analyses using the Cox
      proportional hazard model were performed to explore the most valuable clinical
      characteristic that was associated with postoperative survival. RESULTS:
      Multivariate analysis using twelve clinical characteristics selected from
      univariate analyses revealed that age (<= 72/>72), carcinoembryonic antigen (<=
      20/>20) (ng/ml), white blood cell count (<= 9.5/>9.5) (* 10(3)/mm(3)), prognostic
      nutritional index (PNI) (<= 45/>45) and lymph node metastasis (negative/positive)
      were associated with postoperative survival. Kaplan-Meier analysis and log-rank
      test showed that patients with higher PNI (>45) had a higher postoperative
      survival rate than those with lower PNI (<= 45) (p<0.001). CONCLUSION: PNI is
      associated with postoperative survival of patients undergoing TG for GC and is
      able to divide such patients into two independent groups before surgery.

PMID- 25075052
TI  - Efficacy of transarterial chemoembolization targeting portal vein tumor thrombus
      in patients with hepatocellular carcinoma.
AB  - AIM: We aimed to retrospectively examine the tolerability and efficacy of
      transarterial chemoembolization (TACE) in patients with advanced hepatocellular
      carcinoma (HCC) with portal vein tumor thrombus (PVTT). PATIENTS AND METHODS:
      Adverse events were assessed using the Common Terminology Criteria for Adverse
      Events, version 4.0. The efficacy of TACE in parenchymal tumors (parenchymal
      response) and PVTT (PVTT response) was separately evaluated by dynamic computed
      tomography 1 to 2 months after TACE according to the Response Evaluation Criteria
      in Cancer of the Liver (RECICL). Patients with complete remission plus partial
      response in parenchymal tumors and PVTT were assessed as parenchymal response
      positive and PVTT response-positive, respectively. RESULTS: A total of 33 HCC
      patients with PVTT were analyzed. Grade 3/4 toxicities included elevated
      aspartate aminotransferase levels (69.7%), elevated alanine aminotransferase
      levels (54.5%), hyponatremia (6.1%), thrombocytopenia (6.1%), hyperbilirubinemia
      (3.0%), leukopenia (3.0%) and anemia (3.0%). All these findings returned to the
      pre-treatment levels within 1 month after TACE. The number of parenchymal
      response-positive/negative and PVTT response-positive/negative patients was 20/13
      and 13/20, respectively. Kaplan-Meier analyses revealed that the cumulative
      survival rate was significantly higher in parenchymal response-positive (p=0.04)
      and PVTT response-positive (p<0.01) patients than in their negative counterparts.
      PVTT response was a favorable prognostic factor for overall survival in
      multivariate analysis (p=0.03). CONCLUSION: TACE was feasible in HCC patients
      with PVTT and could improve their survival by showing direct therapeutic effect
      against PVTT.

PMID- 25075053
TI  - Surgical treatment of colorectal cancer pulmonary metastases: 12-year results.
AB  - The objective of the present study was to retrospectively analyze a cohort of
      patients who underwent surgery for colorectal cancer pulmonary metastases during
      a 12-year period. PATIENTS AND METHODS: The sample included 75 patients who were
      monitored in terms of overall survival (OS) and disease-free interval (DFI) in
      relation to patient's age, preoperative values of biomarkers, type of surgery,
      number and size of metastases, occurrence of complications and length of
      hospitalisation. RESULTS: A total of 95 surgical interventions were performed and
      133 metastases were removed. Out of these, 28% of patients were free of any signs
      of relapse or disease progression for 5 years after metastasectomy. Those with
      two or more metastases are 2.3-times more at risk of disease progression. Tissue
      polypeptide specific antigen (TPS) values above the 140 IU/l cut-off point
      increase the risk of progression 3.9-times. The five-year survival rate among the
      group was 45%. Patients with 2 or more metastases are 2.7-times more at risk of
      death. TPS values above the 140 IU/l cut-off increase the risk of death 5.5
      times, and carbohydrate antigen CA19-9 values above the 28 IU/ml cut-off point
      increase the risk of death by 3.2 times. CONCLUSION: The number of metastases and
      the preoperative TPS values are decisive prognostic factors influencing both OS
      and DFI.

PMID- 25075054
TI  - Postoperative radiation therapy for parotid pleomorphic adenoma with close or
      positive margins: treatment outcomes and toxicities.
AB  - AIM: To evaluate the locoregional control and treatment toxicity of patients with
      pleomorphic adenoma after resection with close or positive margins followed by
      postoperative radiation therapy (PORT). PATIENTS AND METHODS: Between 2002 and
      2011, twenty-one patients underwent PORT at the Mount Sinai Beth Israel Medical
      Center for pleomorphic adenoma of the parotid with close or positive margins.
      Four out of the 21 patients (19%) had recurrent lesions. The median dose was 57.6
      Gy (range 55.8-69.96) delivered at 1.8-2.12 Gy/fraction. Treatment and follow-up
      data were retrospectively analyzed for locoregional control as well as acute- and
      late-treatment toxicities. Actuarial survival analysis was also performed.
      RESULTS: Twelve women and 9 men with a median age of 46 (26-65) at PORT were
      included in this study. Eighty-one percent of the cohort had positive resection
      margins while 19% had close margins. At a median follow-up of 92 months, 19/21
      patients (90%) had locoregional control. Two patients who failed had primary
      lesions which recurred locally, and initially had positive margins. The two
      recurrences occurred at 8 months and 12 months. Acute Radiation Therapy Oncology
      Group (RTOG) grade 1 and 2 toxicities were experienced by 11 (52%) and 4 (19%)
      patients, respectively, while 2 (10%) experienced late RTOG grade 1 toxicities.
      No patients experienced any grade 2-4 late toxicities. Actuarial survival was
      100%. CONCLUSION: PORT for patients with pleomorphic adenoma of the parotid gland
      after resection with close or positive margins results in excellent locoregional
      control and low treatment-related morbidity.

PMID- 25075055
TI  - Seminoma patients treated at a minor oncological department during 1986-2010:
      treatment and outcome.
AB  - AIM: To present results for patients with seminoma treated at our University
      Clinic. PATIENTS AND METHODS: All men treated for seminoma in 1986-2010 at the
      Department of Oncology, University Hospital of North Norway were included
      (n=232). Treatment was standardized from 2000 as the Swedish and Norwegian
      Testicular Cancer Project (SWENOTECA) published their first standardised seminoma
      treatment program (SWENOTECA V). RESULTS: The percentage of patients administered
      adjuvant radiotherapy (RT) for clinical stage (CS) I decreased gradually from the
      late 1990s and was abandoned in 2005. Surveillance was the most common management
      strategy for CS I after 2000. Overall, disease in 1.9% and 11% of patients
      relapsed after adjuvant RT and surveillance, respectively. There were no relapses
      after treatment for metastatic disease. Cancer-specific survival was 100%, and
      overall survival 95% for the total group. CONCLUSION: The treatment outcome at
      our University Clinic is excellent with 100% cancer-specific survival, and is
      essentially a result of the bi-national SWENOTECA network.

PMID- 25075056
TI  - Feasibility of simultaneous integrated boost IMRT (SIB-IMRT) for castration
      resistant prostate cancer.
AB  - AIM: We examined the feasibility of local intensity-modulated radiation therapy
      (IMRT) with pelvic irradiation using the simultaneous integrated boost (SIB)
      technique to treat patients with castration-resistant prostate cancer (CRPC)
      after several lines of hormonal therapy. PATIENTS AND METHODS: Data from 10
      consecutive patients with CRPC treated with SIB-IMRT between November 2001 and
      September 2009 were analyzed retrospectively. RESULTS: A decline in prostate
      specific antigen (PSA) level was observed in all cases after SIB-IMRT.
      Biochemical progression-free survival at 5 years was 70% with a median follow-up
      of 33.5 months after SIB-IMRT. All patients completed SIB-IMRT without delay due
      to acute toxicity. The PSA nadir after first-line hormonal therapy, the PSA
      before SIB-IMRT, the PSA doubling time before SIB-IMRT and the PSA nadir after
      SIB-IMRT were significant factors for biochemical progression after SIB-IMRT.
      CONCLUSION: SIB-IMRT for patients with CRPC is feasible and has a satisfactory
      effect in terms of disease control.

PMID- 25075057
TI  - Macroscopic type is a prognostic factor for recurrence-free survival after
      resection of gastric GIST.
AB  - BACKGROUND: Accurate evaluation of the biological behavior of Gastrointestinal
      stromal tumor and careful selection of patients with a high risk for tumor
      recurrence are necessary. In the present study, we analyzed prognostic factors in
      patients with GIST. PATIENTS AND METHODS: A total of 214 patients who had
      undergone curative resection of a localized primary gastric GIST without adjuvant
      therapy were enrolled in this retrospective study. Prognostic factors were
      analyzed. The growth pattern was classified as intramural, endoluminal,
      exoluminal, or mixed- type. RESULTS: On univariate and multivariate analyses,
      recurrence was predicted by exoluminal or mixed-type (hazard ratio [HR]=3.7,
      p=0.043), tumor size of >3.5 cm (HR=7.1, p=0.01), and mitotic rate of >5/50 high
      power fields (HR=7.9, p<0.001). CONCLUSION: It is suggested that exoluminal or
      mixed-type is independently associated with recurrence of surgically resected
      gastric GIST in addition to tumor size and mitotic rate.

PMID- 25075058
TI  - Immunohistochemical features associated with sensitivity to lapatinib-plus
      capecitabine and resistance to trastuzumab in HER2-positive breast cancer.
AB  - AIM: To identify immunohistochemical (IHC) features associated with sensitivity
      to lapatinib-plus-capecitabine (LX) and resistance to trastuzumab in human
      epidermal growth factor receptor (HER)-2-positive metastatic breast cancer.
      PATIENTS AND METHODS: Expression levels of estrogen receptor, progesterone
      receptor, epidermal growth factor receptor, HER2, HER3/phosphorylated HER3
      (pHER3), phosphatase and tensin homolog, thymidylate synthase (TYMS), and
      thymidine phosphorylase by IHC were compared between patients treated with LX
      following trastuzumab failure. RESULTS: In 35 patients, HER2 was the only
      biomarker associated with LX treatment outcomes. A high HER2 level was associated
      with significantly longer survival and a tendency towards longer time-to
      progression and higher response rates. Acquisition of trastuzumab resistance was
      associated with higher pHER3 and TYMS expression. Elevated pHER3 was predictive
      of superior treatment outcomes. CONCLUSION: Up-regulation of pHER3 and TYMS was
      associated with trastuzumab resistance. High HER2 and increased pHER3 IHC levels
      correlated with favourable LX treatment outcomes in patients with HER2-positive
      metastatic breast cancer.

PMID- 25075059
TI  - Radio-chemotherapy with temozolomide in elderly patients with glioblastoma. A
      mono-institutional experience.
AB  - AIM: The aim of the present study was to evaluate the toxicity and clinical
      outcome of radio-chemotherapy with temozolomide in patients with glioblastoma
      aged more than 65 years. MATERIALS AND METHODS: The analysis was performed in 20
      male and 20 female patients with a mean age at diagnosis of 71.2 (range=65-81)
      years, with Karnofsky performance status greater than 70 without important
      comorbidities. RESULTS: Toxicities related to temozolomide and concomitant
      radiochemotherapy were similar to those reported for younger patients. The median
      time to progression and median overall survival of the entire cohort, from the
      date of diagnosis, were 10.6 (range=6.7-14.4) months and 19.3 (range=17.8-20.7)
      months, respectively. No significant results for overall survival analysis were
      found for age at diagnosis and cardiovascular risk factors, as covariates, with
      hazard ratios of 1.00 (95% confidence interval=0.92-1.10) and 0.9 (95% confidence
      interval=0.43-1.88), respectively. CONCLUSION: Considering the relative good
      toxicity profile and the efficacy of treatment, our experience supports the use
      of radiochemotherapy with temozolomide in older patients with glioblastoma.

PMID- 25075060
TI  - Elderly woman with triple-negative metastatic breast cancer successfully treated
      with metronomic capecitabine.
AB  - Triple-negative breast cancer phenotype (estrogen receptor-, progesterone
      receptor- and human epidermal growth receptor 2-negative) is one of the most
      aggressive molecular subtypes, accounting for 15-20% of all breast tumors. There
      is no standard treatment for this setting of patients except anthracyclines and
      taxanes, but not all elderly patients can tolerate these kinds of agents. We
      describe the case of an elderly woman affected by triple-negative breast cancer
      with bone and brain metastases who has been treated for five years with
      metronomic capecitabine. At the moment, the patient has stable disease and enjoys
      good quality of life. She had initially been diagnosed with a poor Karnofsky
      index, which has actually improved from 50 to 90. Metronomic capecitabine
      treatment has clearly improved her quality of life, as documented by the results
      of the Functional Assessment of Cancer Therapy Breast. 

PMID- 25075061
TI  - Postoperative functional evaluation of gastric tube after laparoscopic proximal
      gastrectomy for gastric cancer.
AB  - BACKGROUND: The primary aim of this study was to examine the motor activity
      (motility) of a gastric tube after laparoscopic-assisted proximal gastrectomy
      (LPG). A secondary objective was to ascertain whether a correlation exists
      between gastric tube motor activity and reflux esophagitis. PATIENTS AND METHODS:
      A total of 41 patients who underwent LPG for early gastric cancer were studied.
      The motility of the gastric tube and the status of reflux esophagitis were
      evaluated. Manometric recording was performed 2 weeks and 1 year after surgery.
      RESULTS: In a fasting state, the motilities of the distal gastric tube and
      duodenum recovered within 1 year after surgery but that of the proximal gastric
      tube did not recover. Improvement of the motility of the gastric tube was
      associated with a decreased number of patients with reflux esophagitis 1 year
      after surgery. In patients with reflux esophagitis, the motility of the distal
      gastric tube was significantly lower than that in patients without reflux
      esophagitis. CONCLUSION: After LPG, the motility of the gastric tube recovered,
      and the incidence of reflux esophagitis decreased with time, in parallel to
      recovery of gastrointestinal motility.

PMID- 25075062
TI  - Renal Insufficiency in newly-diagnosed multiple myeloma: analysis according to
      International Myeloma Working Group consensus statement.
AB  - Renal impairment (RI) is one of the key clinical manifestations of symptomatic
      multiple myeloma. However, the incidence of RI and renal response to treatment
      are variable depending on their definition. A total of 379 patients newly
      diagnosed and treated for symptomatic myeloma at the Samsung Medical Center
      between January 2000 and December 2011 were retrospectively reviewed. RI and
      renal response were assessed according to the recent International working group
      (IMWG) recommendations. Out of the 379 patients, renal insufficiency was present
      in 117 (30.8%) and was associated with adverse clinical parameters such as
      anemia, elevated beta-2 microglobulin (B2M), elevated lactate dehydrogenase
      (LDH), hypercalcemia, and more advanced disease by the International Staging
      System (ISS). Out of the 85 patients who were evaluable for renal response, 58
      (68.2%) showed renal response and 46 (54%) had major renal response. Less
      advanced disease by the International Staging System and inclusion of high-dose
      dexamethasone as first-line treatment were independently predictive for major
      renal response. Median time-to-renal response was 5.5 months, and bortezomib
      containing regimen, high-dose dexamethasone, and less advanced stage disease were
      associated with a more rapid renal response. CONCLUSION: The incidence of RI in
      patients with newly-diagnosed multiple myeloma was 31%, and renal response was
      affected by the treatment and staging by the International Staging System.

PMID- 25075064
TI  - Treatment sequence of aromatase inhibitors and radiotherapy and long-term
      outcomes of breast cancer patients.
AB  - BACKGROUND: The optimal sequence of radiotherapy (RT) and hormone therapy using
      aromatase inhibitors (AI) in patients with breast cancer treated with breast
      conserving surgery is unclear. Several short-term analyses have shown that there
      are no differences in breast cancer outcomes according to the treatment sequence.
      However, long-term outcomes have not been reported. PATIENTS AND METHODS: We
      retrospectively analyzed disease-free survival events in 315 consecutive breast
      cancer patients who underwent breast-conserving surgery, RT, and received
      adjuvant AI at our Institute between 2001 and 2009. We compared the outcomes
      between treatment sequences of AI and RT (concurrent vs. sequential). RESULTS:
      With a median follow-up of 5.6 years, no significant differences between the 2
      groups in terms of disease-free survival (unadjusted p=0.6; adjusted p=0.5) were
      observed. CONCLUSION: Similarly to previous short-term reports, AI administration
      after RT and AI concurrently with RT are both reasonable treatment options for
      early-stage breast cancer patients treated with breast-conserving surgery.

PMID- 25075063
TI  - Living donor liver transplantation followed by total gastrectomy--a two-stage
      planed operative strategy for early gastric cancer concomitant with decompensated
      liver cirrhosis.
AB  - AIM: With the recent popularization of living donor liver transplantation (LDLT),
      providing treatment for comorbidities in LDLT recipients has become important. We
      report the first case of a patient who was successfully treated with LDLT
      followed by total gastrectomy for early gastric cancer concomitant with
      decompensated liver cirrhosis. CASE REPORT: A 64-year-old female was admitted for
      the treatment of severe liver cirrhosis. The patient's preoperative liver
      function was evaluated as Child-Pugh classification grade C. Upper
      gastrointestinal endoscopy revealed early gastric cancer. We first performed LDLT
      to improve her liver function and coagulopathy. Nineteen days after the LDLT, we
      performed total gastrectomy. RESULTS: The patient's postoperative course was
      uneventful and she left our hospital on the 18th day after gastrectomy. The final
      pathological diagnosis of gastric cancer was Stage IA. CONCLUSION: Aggressive and
      adequate surgical strategy including LDLT is effective as curative treatment in
      patients with controllable malignancy concomitant with severe liver dysfunction.

PMID- 25075065
TI  - No infectious hepatic complications following radioembolization with 90Y
      microspheres in patients with biliodigestive anastomosis.
AB  - AIM: To retrospectively evaluate infectious hepatic complications of
      transarterial radioembolization (RE) of the liver in patients with pre-existing
      biliodigestive anastomosis. PATIENTS AND METHODS: Patients who underwent RE were
      retrospectively analyzed. All patients had at least a contrast-enhanced magnetic
      resonance imaging or contrast-enhanced triple-phase computed tomographic scan
      before and 6-8 weeks after RE. RESULTS: Overall, 143 patients (67 women, 76 men;
      median age = 65 +/- 11.2 years) were analyzed. Nine patients had a biliodigestive
      anastomosis. The complications were as follows: one case of cholecystitis, three
      of gastroduodenal ulcer with one ulcer perforation, and six of radioembolization
      induced liver disease. There were no infectious complications. There were no
      major or minor complications in the group with previous biliodigestive
      anastomosis. CONCLUSION: Pre-existing bilioenteric anastomoses are not a negative
      predictive factor for the development of infectious hepatic complications after
      RE. RE with (90)Y microspheres can be safely performed following careful patient
      selection.

PMID- 25075066
TI  - Silibinin administration improves hepatic failure due to extensive liver
      infiltration in a breast cancer patient.
AB  - BACKGROUND: Silibinin exerts hepatoprotective, anti-inflammatory and anti
      fibrotic effects. Several pre-clinical studies have shown anti-tumoral activity
      of silibinin in breast cancer cell lines. CASE REPORT: We present the case of a
      heavily pre-treated breast cancer patient with extensive liver infiltration. The
      patient presented with progressive liver failure despite several chemotherapy
      treatments, including paclitaxel, capecitabine and vinorelbine. After four cycles
      of a fourth-line chemotherapy treatment consisting of carboplatin and
      gemcitabine, the patient's liver blood test results deteriorated to life
      threatening levels. The compassionate use of Legasil(r), a new commercially
      available nutraceutical product containing a new silibinin formulation, was
      offered to the patient according to article 37 of the 2013 Declaration of
      Helsinki. After treatment initiation, the patient presented clinical and liver
      improvement, which permitted the patient to continue palliative chemotherapy.
      CONCLUSION: This is the first case report of a clinical benefit of silibinin
      administration in a breast cancer patient.

PMID- 25075067
TI  - Sunitinib for patients with metastatic non-clear cell renal cell carcinoma: a
      Multicenter Retrospective Turkish Oncology Group trial.
AB  - AIM: This study aimed to assess the clinical efficacy and toxicity of sunitinib,
      a targeted-agent, for non-clear cell renal cell carcinoma. PATIENTS AND METHODS:
      Sixty-three patients with complete clinical data from 13 oncology Centers were
      retrospectively evaluated. Outcomes analyzed were objective response rate (ORR),
      progression-free survival (PFS), overall survival (OS) and adverse events.
      RESULTS: The median age of all patients, 38 men (60.3%) and 25 women (39.7%), was
      63 years (range=25-82 years). Histological subtypes included 46 (88%) cases of
      papillary RCC, 10 of chromophobe, and 7 unclassified cases. Median treatment
      duration was seven months (range=2-86 months). At the time of this analysis, 52
      patients had discontinued treatment, 33 of whom had died. Treatment
      discontinuation was due to disease progression in 43 patients, and toxicity in
      nine. Dose interruption was necessary in 22 (34.9%) patients, and dose reduction
      in 27 (42.9%). The objective response rate and disease control rate were 11.1%
      and 63.5%, respectively. The median PFS and OS were 7.6 months (95% confidence
      interval (CI)=5.5-9.7 months) and 22.0 months (95% CI=13.4-30.6 months),
      respectively, with 1-year rates of 64.7% and 33.7%, respectively. CONCLUSION:
      Clinical outcome of the metastatic non-clear cell RCC patients with sunitinib
      treatment seemed to be worse than the historical data of clear cell RCC patients,
      in terms of PFS, OS and objective response. New and more effective targeted
      therapies and better understanding of the underlying molecular processes are
      necessary to improve survival outcome for these patients.

PMID- 25075068
TI  - Detection and characterization of focal liver lesions by split-bolus
      multidetector-row CT: diagnostic accuracy and radiation dose in oncologic
      patients.
AB  - AIM: To assess the diagnostic accuracy and radiation dose of split-bolus
      multidetector-row computed tomography (MDCT) protocol in the detection and
      characterization of focal liver lesions in oncologic patients. PATIENTS AND
      METHODS: We retrospectively analyzed triphasic CT at initial diagnosis and follow
      up split-bolus 64-detector row CT protocol in 48 oncologic patients with focal
      liver lesions. Split-bolus MDCT protocol by i.v. injection of two boli of
      contrast medium combines hepatic arterial phase (HAP) and hepatic enhancement
      during portal venous phase (PVP) in a single pass. First bolus: 75-90 mL at 2.0
      mL/sec to obtain adequate hepatic enhancement during the PVP; second bolus: 60
      mL/sec at 3.5 mL/sec to ensure HAP. Each bolus is followed by 20 mL of saline
      solution at the same flow rate. Sensitivity, specificity, positive predictive
      value and negative predictive value of split-bolus MDCT protocol were calculated
      for detection and characterization of liver lesions. The effective radiation dose
      (ED) was calculated using dose-length product (DLP) values in mSv determined
      using a conversion factor. RESULTS: compared to triphasic-MDCT, split-bolus MDCT
      protocol confirmed all the 210 lesions identified and characterized by triphasic
      MDCT technique, unchanged during the follow-up. The mean ED was 27.8 +/- 6 mSv
      for chest-abdomen-pelvis biphasic split-bolus MDCT and 45.7 +/- 13.6 mSv for
      triphasic-MDCT. CONCLUSION: The diagnostic efficacy of split-bolus protocol is
      comparable to that of triphasic protocol at MDCT with a reduction in radiation
      dose of approximately 35-40%.

PMID- 25075069
TI  - Surgical approach and long-term clinical outcome in women with microinvasive
      cervical cancer.
AB  - AIM: To assess the efficacy and safety of conservative surgical approach for
      microinvasive cervical cancer with regards to cone margins status and lymph
      vascular space invasion (LVSI). PATIENTS AND METHODS: This was a multicentre
      retrospective cohort study of 153 women diagnosed with microinvasive cervical
      cancer over a 10 years period (1993-2003). RESULTS: In conservatively-treated
      women (n=80), neither cancer mortality nor disease relapse after 184.5 +/- 20.5
      months of follow-up was detected. Residual disease in women who underwent
      secondary surgery was significantly related to positive margins on the primary
      cone excision (p=0.005) while no correlation with LVSI emerged. CONCLUSION:
      Conization can represent the definitive treatment for stage IA1, if surgical
      margins are cancer-free, independently of LVSI. A conservative surgical approach
      could also be considered in women with IA2 cervical cancer when preservation of
      fertility is strongly requested. A close long-term surveillance should be
      scheduled for conservatively-treated women.

PMID- 25075070
TI  - Biologic factors associated with tumor oxygenation are prognostic in patients
      with stage III esophageal cancer: long-term results.
AB  - BACKGROUND/AIM: Long-term results of a study investigating potential prognostic
      factors for treatment outcomes in patients with stage III esophageal cancer are
      presented. PATIENTS AND METHODS: In 64 patients, the impact of tumor cell
      expression of erythropoietin (EPO) and erythropoietin-receptor (EPO-R) and ten
      additional factors (age, gender, performance status, tumor length, tumor stage (T
      stage), nodes (N-stage), histology/grading, hemoglobin levels during
      radiotherapy, surgery) on survival and loco-regional control was evaluated up to
      10 years following radio-chemotherapy. RESULTS: On multivariate analysis,
      improved survival was associated with low EPO-R expression (p=0.034) and
      hemoglobin levels during radiotherapy >= 12 g/dl (p=0.026). Low EPO expression
      was associated with survival on univariate (p=0.010) but not on multivariate
      analysis (p=0.42). On multivariate analysis, improved loco-regional control was
      significantly associated with hemoglobin levels during radiotherapy >= 12 g/dl
      (p<0.001). CONCLUSION: The long-term results confirm that hemoglobin levels
      during radiotherapy and tumor cell expression of EPO-R are significant prognostic
      factors in patients with locally advanced esophageal cancer.

PMID- 25075071
TI  - Predicting survival after whole-brain irradiation for cerebral metastases from
      prostate cancer.
AB  - BACKGROUND/AIM: Prostate cancer patients represent a small minority of those
      presenting with cerebral metastases. Knowledge about overall survival (OS)
      contributes to individualization of treatment concepts. In this study an OS score
      was created for patients receiving whole-brain irradiation (WBI) for cerebral
      metastases from prostate cancer. PATIENTS AND METHODS: Of six variables, four
      were significantly associated with OS: performance status, time from diagnosis of
      prostate cancer to WBI, number of cerebral lesions, extracranial metastases.
      RESULTS: Six-month OS rates of the four variables (in %, divided by 10) were
      added. The addition resulted in scores of 1 to 19 points. Six-month OS rates were
      0% for <15 points and 100% for >= 15 points (p<0.001). CONCLUSION: An OS score
      was generated specifically for patients with cerebral lesions from prostate
      cancer. For patients with <15 points, a short WBI regimen (5x4 Gy) should be
      used, for patients with >= 15 points a longer regimen seems appropriate.

PMID- 25075072
TI  - Definitive extended-field intensity-modulated radiotherapy with chemotherapy for
      cervical cancer with para-aortic nodal metastasis.
AB  - AIM: To evaluate the efficacy and toxicity of definitive extended-field intensity
      modulated radiotherapy (EF-IMRT) with chemotherapy in cervical cancer with para
      aortic lymph node (PAN) metastasis. PATIENTS AND METHODS: The present
      retrospective cohort study involved 45 consecutive patients. EF-IMRT consisted of
      46 Gy to pelvic and para-aortic regions, 14 Gy-boost to gross nodes, and 30 Gy in
      six fractions of intracavitary brachytherapy. Platinum-based chemotherapy
      occurred simultaneously. RESULTS: Two-year overall and disease-free survival
      rates (median follow-up=30 months) were 85.4% and 61.7%, respectively. In 78%,
      89%, and 89%, the primary cervical mass, pelvic metastasis, and PAN metastasis
      exhibited a complete response, respectively. Ten, four, and other four patients
      exhibited locoregional (including post-treatment residual disease), distant, and
      combined failure, respectively. The most common severe acute toxicity was
      hematological (n=36). One and two patients had severe late gastrointestinal and
      other toxicities, respectively. CONCLUSION: EF-IMRT (to 60 Gy) plus chemotherapy
      resulted in good locoregional control, survival rates, and acceptable toxicity.

PMID- 25075073
TI  - Usefulness of resection for hepatocellular carcinoma with macroscopic bile duct
      tumor thrombus.
AB  - BACKGROUND: The prognostic significance of bile duct tumor thrombus (BDTT) in
      hepatocellular carcinoma (HCC) is unclear and the usefulness of resection for HCC
      with BDTT is still controversial. The aim of the present study was to evaluate
      the impact of BDTT on prognosis in HCC and to determine whether resection of HCC
      with BDTT was useful. PATIENTS AND METHODS: Out of 820 HCC patients who underwent
      hepatic resection from 1992 to 2012, 13 HCC patients (1.6%) had macroscopic BDTT.
      The results of resection for HCC patients with BDTT and the prognostic
      significance of BDTT were evaluated. Prognoses were also compared according to
      treatment in patients who had HCC with BDTT. RESULTS: The overall 1-, 3- and 5
      year survival rates after resection were 92%, 77% and 48%, respectively, for HCC
      patients with BDTT, and 88%, 67%, and 52%, respectively, for HCC patients without
      BDTT; there were no significant differences (p=0.833). In all HCC patients after
      resection, the unadjusted hazard ratio of the presence of BDTT was 1.08
      (95%CI=0.49-2.05; p=0.835) and when adjusted for other significant prognostic
      factors, the hazard ratio of the presence of BDTT was 0.98 (95%CI=0.42-1.98;
      p=0.958). The overall 1-, 3- and 5-year survival rates were 14%, 5% and 0%,
      respectively, for 25 HCC patients with BDTT after other initial treatments.
      CONCLUSION: Bile duct tumor thrombus was not a prognostic factor in patients with
      resected HCC. In HCC with BDTT, surgical treatment is recommended whenever
      possible because only resected patients achieved long-term survival.

PMID- 25075074
TI  - Age does not worsen the efficacy nor tolerance to combined induction therapies in
      locally advanced non-small cell lung cancer.
AB  - BACKGROUND: One third of non-small cell lung cancer (NSCLC) affects elderly
      patients in a locally advanced (LA) stage. Induction therapy followed by a
      curative approach is becoming the standard-of-care for LA-NSCLC. PATIENTS AND
      METHODS: We compared the efficacy and tolerance to induction chemotherapy or
      chemo-radiation followed by surgery or definitive radiotherapy in patients
      younger (N=64) and older (N=44) than 70 years with LA-NSCLC. RESULTS: Elderly
      patients trended towards having a worse baseline performance status, and
      presented a higher percentage of IIIB, and squamous tumors. Nevertheless, no
      significant differences in response rate, operability, or disease-free and
      overall survival were found between age groups in the whole series, nor in the
      sub-group of resected patients. Grade 3-4 toxicity tended to be lower in elderly
      patients. CONCLUSION: Age by itself did not significantly worsen either the
      efficacy or tolerance to combined induction and definitive treatment in patients
      with LA-NSCLC and Eastern Cooperative Oncology Group performance status 0-2.

PMID- 25075075
TI  - Primary diffuse large B-cell lymphoma of the uterus: case report and review.
AB  - BACKGROUND: Primary diffuse large B-cell lymphoma of the cervix is a very rare
      disease, with non-specific clinical presentation. Its prognosis depends on
      accurate and timely diagnosis and therapy. Moreover, the management of this
      tumour has never been standardized. CASE REPORT: Herein we present a rare case of
      primary diffuse large B-cell lymphoma of the cervix misdiagnosed as cervical
      myoma. Our systematic review of the English literature identified 143 cases of
      primary diffuse large B-cell lymphoma of the uterus. Patients' characteristics
      and oncological, surgical, and safety data were recorded and analyzed.
      CONCLUSION: Although rare, primary diffuse large B-cell lymphoma of the cervix
      should never be ruled-out. Given its non-specific clinical symptoms, a
      multidisciplinary approach is required to perform a timely diagnosis and
      administer appropriate therapy. Immunochemotherapy (Rituximab + CHOP or CHOP-like
      regimen) with/without radiotherapy is the most common and most effective
      treatment; surgery should be avoided.

PMID- 25075076
TI  - Recurrence patterns of esophagogastric junction adenocarcinoma according to
      Siewert's classification after radical resection.
AB  - BACKGROUND: The treatment strategy for adenocarcinoma of the esophagogastric
      junction (AEG) remains controversial. In the present study, the recurrence
      pattern of AEGs according to Siewert's classification after radical resection was
      reviewed, and predictive factors of recurrence were examined. PATIENTS AND
      METHODS: We retrospectively analyzed the clinical data of 127 consecutive
      patients with Siewert type I, II, and III AEGs who underwent curative resection
      (R0) without perioperative chemotherapy at the National Cancer Center Hospital
      East between January 1993 and November 2006. RESULTS: The median follow-up period
      was 48.9 (range=1.5-179) months. The recurrence rates of type I, II, and III
      tumors were 57.1%, 44.4%, and 41.0%, respectively. The most frequent relapse site
      was lymphogenous in type I, hematogenous in type II, and disseminative in type
      III tumors. The median time-to-recurrence after surgery was 12.6 months in type
      I, 12.5 months in type II, and 12.7 months in type III disease, with no
      significant difference. Multivariate analysis revealed that mediastinal lymph
      node metastasis (p=0.005) (hazard ratio=2.954, 95% Confidence Interval=1.38-6.31)
      was a significant and independent prognostic indicator for poor recurrence-free
      survival. The recurrence rate in patients with mediastinal lymph node metastasis
      at the time of surgery was 100%. CONCLUSION: The recurrence pattern of AEGs
      differed according to Siewert's classification. Its tendency should be understood
      in order to determine the optimal surgical approach. Mediastinal lymph node
      dissection may be effective for local control, but may not significantly improve
      prognosis. When mediastinal lymph node metastasis is suspected, perioperative
      chemotherapy may be recommended.

PMID- 25075077
TI  - Prognostic impact of hepatectomy for patients with non-hepatitis B, non-hepatitis
      C hepatocellular carcinoma.
AB  - BACK GROUND/AIM: The purpose of the present study was to clarify the
      clinicopathological features of non-hepatitis B and -C (NBNC) hepatocellular
      carcinoma (HCC), the incidence of which has been increasing. PATIENTS AND
      METHODS: Two hundred and eighty-four patients with HCC were classified into three
      groups according to viral hepatitis status, namely NBNC, hepatitis B, and
      hepatitis C. We compared the three groups and studied related risk factors.
      RESULTS: Patients without cirrhosis who had increased number of platelets and
      diabetes mellitus, and a serum alpha-feto-protein (AFP) level <100 ng/dl were
      more common in the NBNC group. The cumulative survival and disease-free survival
      were better in the NBNC group than in the other groups. The tumor size and
      hepatitis B or C viral status were found to be independent risk factors of
      disease-free survival and the presence of multiple lesions was the only
      independent risk factor of survival. CONCLUSION: Close follow-up of NBNC liver
      cirrhosis and early detection of NBNC-HCC can improve the prognosis after
      surgery.

PMID- 25075078
TI  - A case of herpes simplex-associated encephalitis after brain irradiation for lung
      cancer metastases.
AB  - BACKGROUND: Encephalitis caused by Herpes Simplex Virus-1 is a devastating
      disease with high mortality and disability rates despite adequate treatment. No
      clear risk factors have been identified although iatrogenic immunosuppression has
      been suggested, among others. CASE REPORT: A 59-year-old male smoker was
      diagnosed with metastatic lung adenocarcinoma and was treated with brain and
      spinal irradiation. Ten days after the completion of radiotherapy and before
      initiating platinum-based front-line chemotherapy, he developed low grade fever
      and personality change. Over the next few days, high fever and refractory
      seizures developed and the patient was diagnosed with Herpes simplex-associated
      encephalitis after detection of viral DNA in the cerebrospinal fluid via
      polymerase chain reaction. Despite treatment with acyclovir, the patient remained
      comatose and died three months after the initial presentation. CONCLUSION: This
      case illustrates a possible association between brain irradiation and increased
      risk for Herpes simplex-associated encephalitis. However, the underlying
      mechanisms have not been elucidated.

PMID- 25075079
TI  - Zoledronic acid improves clinical outcomes in patients with bone metastatic
      hormone-naive prostate cancer in a multicenter clinical trial.
AB  - AIM: To assess whether zoledronic acid (ZOL) adds to the effect of combined
      androgen blockade (CAB) in patients with hormone-naive bone metastatic prostate
      cancer. PATIENTS AND METHODS: Patients were treated with either a combination of
      CAB (luteinizing hormone-releasing hormone agonist and bicalutamide) and ZOL (CAB
      Z group) or CAB-alone (historical control patients, CAB-C group). ZOL was
      injected intravenously at 4 mg every 4 weeks. One hundred and five and 100
      patients among 205 enrolled patients were assigned to the CAB-Z group and CAB-C
      group, respectively. The time to prostate-specific antigen (PSA) failure in
      patients in the CAB-Z group was compared to that in the CAB-C group. The primary
      end-point of the study was the time-to-PSA failure. RESULTS: PSA and serum N
      telopeptide of type I collagen (NTx) levels were examined before treatment and
      every 3 months after treatment. PSA failure occurred in 42 (40.0%) patients in
      the CAB-Z group and 48 (48.0%) patients in the CAB-C group. The biochemical
      recurrence-free rate was significantly lower in patients in the CAB-C group
      (p=0.004, by log-rank test). The categorical biopsy Gleason score pre-treatment
      serum NTx and treatment with ZOL were shown to be independent predictors of PSA
      failure-free survival time (p=0.040, p=0.005 and p=0.026, respectively).
      CONCLUSION: ZOL given with CAB as initial treatment delays the time-to-PSA
      failure in patients with hormone-naive bone metastatic prostate cancer.

PMID- 25075080
TI  - Surgical outcomes of anatomical resection for solitary recurrent hepatocellular
      carcinoma.
AB  - BACKGROUND: For eradicating portal venous tumor extension and intrahepatic
      metastasis in hepatocellular carcinoma (HCC), anatomical resection is, in theory,
      preferable. PATIENTS AND METHODS: We carried-out a retrospective cohort study in
      110 patients who underwent curative hepatic resection (anatomical resection;
      n=20, and limited resection; n=90) for solitary recurrent HCC from 1990-2010.
      RESULTS: No significant difference was found in short-term surgical results such
      as mortality, morbidity, and duration of hospital stay between the two groups.
      Anatomical resection did not influence overall and disease-free survival for all
      patients with a solitary recurrent HCC. In patients with cancer spread, such as
      pathological vascular invasion and intrahepatic metastasis (n=61), or with des
      gamma-carboxy prothrombin (DCP) >= 100 mAU/ml (n=73), the disease-free survival
      rate in the anatomical-resection group was significantly better than that in the
      limited-resection group (p=0.0452 and p=0.0345, respectively). CONCLUSION:
      Anatomical resection should be recommended only for HCC suspected of exhibiting
      cancer spread as reflected by DCP >= 100 mAU/ml in patients with solitary
      recurrent HCC.

PMID- 25075081
TI  - Hypothyroidism after radiotherapy for primary thyroid lymphoma.
AB  - BACKGROUND: Thyroid lymphoma is rare, with no standard therapeutic protocol.
      Radiotherapy is often employed. PATIENTS AND METHODS: Nine patients who had
      received radiotherapy for thyroid lymphoma in our Institute, from September 2005
      to August 2013, were reviewed for hypothyroidism. The median radiation dose was
      40 Gy. Thyroid-stimulating hormone (TSH) levels were measured before and after
      radiotherapy, and hypothyroidism was defined as a TSH level exceeding 10 mIU/l.
      Peak TSH was defined as the highest TSH level during the follow-up period.
      RESULTS: The complete response rate was 77.8%, and the 5-year overall survival
      rate was 74.1%. The median time-to-peak TSH was 162.5 days after the start of
      radiotherapy. Hypothyroidism was diagnosed in three (37.5%) out of eight patients
      without thyroidectomy. CONCLUSION: Hypothyroidism is a frequent complication of
      radiotherapy for thyroid lymphoma.

PMID- 25075082
TI  - Longitudinal analysis of late vaginal mucosal reactions after high-dose-rate
      brachytherapy in patients with gynecological cancer.
AB  - AIM: To longitudinally examine the late vaginal mucosal reactions in patients
      following high-dose-rate brachytherapy (BT). PATIENTS AND METHODS: We examined
      late vaginal mucosal reactions in 100 patients using the modified Dische score at
      6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 37
      interstitial BTs and 63 conventional intracavitary BTs, with a median follow-up
      of 41 months (range=6-144 months). RESULTS: There were no cases of lethal
      toxicity or severe toxicity requiring surgery. Bleeding or discharge grade 1 or
      more was exhibited by fewer than 2-4% of patients, and in most cases only until
      1.5 years following treatment. Erythema was detected in approximately 30% (mainly
      grade 1) of the patients up to five years. With regard to ulceration, four
      patients (7%) developed superficial ulceration; however, no patient had
      ulceration lasting six months or longer. Telangiectasia increased gradually over
      time in approximately 91% of patients (grades 1 and 2=73% and 18%, respectively)
      in the five years following treatment. The pallor reaction also increased over
      time in 100% of patients (grades 1, 2, and 3=30%, 48%, and 22%, respectively) in
      the five years after treatment. Stenosis also increased with time in
      approximately 97% of patients (grades 1, 2, and 3=29%, 61%, and 7%, respectively)
      over five years. There was a close correlation between pallor reaction and
      stenosis. CONCLUSION: High-dose-rate BT caused mild-to-moderate toxicities.
      Almost all patients showed pallor reaction, telangiectasia, and stenosis up to
      five years after treatment, and pallor reaction correlated with stenosis.

PMID- 25075083
TI  - Detection of thyroid cancer by an FDG-PET cancer screening program: a Japanese
      nation-wide survey.
AB  - BACKGROUND/AIM: The [(18)F]-fluorodeoxyglucose positron emission tomography (FDG
      PET) cancer screening program is defined as a cancer screening for asymptomatic
      subjects using FDG-PET (including PET/ computed tomography [CT]) with or without
      combination of other screening tests. The aim of the present study was to analyze
      the thyroid cancer detection rate in asymptomatic individuals through a FDG-PET
      cancer screening program in Japan. MATERIALS AND METHODS: A total of 153,775
      asymptomatic individuals underwent FDG-PET cancer screening. We analyzed 1,308
      cases for possible thyroid cancer in all screening tests. RESULTS: Among the
      1,308 possible cases, 353 were verified as thyroid cancer. The relative
      sensitivity and positive predictive value (PPV) of FDG-PET were 90.7% and 29.5%
      for thyroid cancer, respectively. The relative sensitivity was equivalent to
      thyroid ultrasonography (US) (90.9%) and higher than neck computed tomography
      (CT) (75.7%, p<0.001), thyroglobulin (36.1%, p<0.001), and carcinoembryonic
      antigen (5.6%, p<0.001). The sensitivity with a PET/CT scanner was higher than
      that with a dedicated PET scanner (94.1% vs. 85.0%, p<0.001). Combining thyroid
      US with FDG-PET increased the relative sensitivity and PPV. The majority of
      thyroid carcinomas detected by FDG-PET screening were Union for International
      Cancer Control (UICC) stage I, but a significant number of cases were also
      detected as stage III or IV. CONCLUSION: The FDG-PET cancer screening program in
      Japan detected thyroid cancer at an early stage. FDG-PET showed high sensitivity
      in detecting thyroid cancer, and it may be more effective if combined with
      thyroid US.

PMID- 25075084
TI  - The role of interim 18F-FDG PET/CT in predicting early response to neoadjuvant
      chemotherapy in breast cancer.
AB  - AIM: The aim of this study was to prove the diagnostic value of interim 18F
      Fluorodeoxyglucose-positron-emission tomography combined with computed tomography
      (PET/CT) scan for predicting pathological complete response (pCR) compared to
      other factors in neoadjuvant chemotherapy. PATIENTS AND METHODS: Twenty-seven
      patients with breast cancer were included in this retrospective study. They all
      underwent scheduled neoadjuvant chemotherapy. Patients underwent PET/CT at
      baseline, mid-point (interim), and preoperatively (after completion of
      chemotherapy). The metabolic response was calculated as follows:
      DeltaStandardized uptake value (SUV)(%)=(1st SUV(max)-2nd SUV(max))/1st SUV(max)
      * 100. RESULTS: The change in SUVmax between baseline and interim PET/CT scans
      was significantly larger than between interim and preoperative PET/CT scan. An
      optimal cut-off DeltaSUV value of 78.3% was proposed for discriminating patients
      with pCR from those without pCR. Metabolic CR, defined as a change of SUV(max)
      greater than the cut-off value, can predict pCR according to univariate analysis
      (p=0.012; Relative risk (RR)=25.3). Furthermore, metabolic CR was the most
      powerful factor for predicting pCR than other possible factors according to
      multivariate analysis (p=0.003). CONCLUSION: It is possible to use interim (18)F
      FDG PET-CT as an effective method to predict early response in patients with
      breast cancer treated with neoadjuvant chemotherapy.

PMID- 25075085
TI  - Clinical significance of urokinase-type plasminogen activator (uPA) and its type
      1 inhibitor (PAI-1) for metastatic sentinel lymph node involvement in breast
      cancer.
AB  - Urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) are
      key factors for tumor invasion and development of metastases in breast cancer.
      Prospective studies confirmed the prognostic significance of these factors for
      development of distant metastases. The predictive impact of uPA and PAI-1 for
      metastatic sentinel lymph node involvement is unclear. PATIENTS AND METHODS:
      Between 2006 and 2008 uPA and PAI-1 were measured in 184 out of 1,035 patients
      for primary breast cancer. uPA and PAI-1 were analyzed with an ELISA assay.
      Measured concentrations were considered as negative for uPA <3 ng/ml and for PAI
      1 <14 ng/ml. RESULTS: In a retrospective analysis, 173/184 women had a negative
      sentinel lymph node and 11/184 women had a metastatic sentinel lymph node. From
      the 11 women with a positive sentinel lymph node 7 had elevated values for uPA
      and 4 had elevated values for PAI-1. Four and 7 women were uPA- and PAI-1
      negative, respectively. Sensitivity, specificity, positive and negative
      predictive values for uPA were 63.3%, 50.9%, 7.6%, 95.6% and for PAI-1 36%,
      52.6%, 4.7%, 92.9%. Even the combination of both uPA and PAI-1 values did not
      detect 3/11 women with metastatic lymph node involvement. CONCLUSION: uPA and PAI
      1 alone or in combination did not identify all patients with metastatic lymph
      node involvement. Thus, uPA and PAI-1 cannot be considered as predictive
      selection parameters to avoid sentinel lymph node biopsy in case of negative
      values for uPA or PAI-1.

PMID- 25075086
TI  - Clinicopathological characteristics and prognosis of patients according to
      recurrence time after radical nephrectomy for localized renal cell carcinoma: a
      multicenter study of Anatolian Society of Medical Oncology (ASMO).
AB  - AIM: We investigated the clinicopathological features in patients with recurrent
      RCC within 5 years or more than 5 years after nephrectomy and determined
      predictors of survival and response treatment after recurrence. MATERIALS AND
      METHODS: We retrospectively evaluated 144 patients with disease recurrence; 73
      had recurrence more than 5 years after radical nephrectomy. We compared
      clinicopathological characteristics in patients with disease recurrence before
      vs. after 5 years. In addition, we investigated predictors of survival and
      response to treatment after recurrence. RESULTS: Seventy-one patients (49%) were
      diagnosed with recurrence within 5 years after radical nephrectomy (early
      recurrence) and 73 patients (51%) were diagnosed with recurrence more than 5
      years after radical nephrectomy (late recurrence). Fuhrman grade, tumor necrosis
      and lymphovascular invasion were statistically significantly different between
      the two groups (p<0.001, p=0.013, p=0.026, respectively). The late recurrence
      patients were significantly associated with the Memorial Sloan Kettering Cancer
      Center (MSKCC) favorable risk group compared to patients with early recurrence
      (p=0.001). From the time of disease recurrence, median Overall Survival (OS) was
      36.0 (95% Confidence Interval (CI) 30.7-41.2) months in the late recurrence
      group, and 19 (95% CI 15.4-22.5) months in the early recurrence group (p=0.01).
      The median Progression Free Survival (PFS) was 6 (95% CI 3.87-8.12) months in the
      early recurrence group, and 18 (95% CI 15.4-20.5) months for the late recurrence
      group (p<0.001). CONCLUSION: Early recurrence was significantly associated with
      Fuhrman grade 3-4, tumor necrosis, lymphovascular invasion, MSKCC poor-risk group
      compared to patients with late recurrence. The study also demonstrated a
      potential prognostic value of late recurrence in terms of PFS and OS.

PMID- 25075087
TI  - Prediction of lymph node metastasis in patients with submucosa-invading early
      gastric cancer.
AB  - BACKGROUND AND AIM: Early gastric cancer (EGC), with wall invasion limited to the
      submucosa, has approximately 15 to 20% chance of lymph node metastasis. The
      purpose of this study is to clarify the parameters which affect lymph node
      metastasis and survey whether lymph node metastasis can be predicted
      preoperatively. PATIENTS AND METHODS: We retrospectively analyzed 145 consecutive
      patients with EGC using multivariate analysis and developed a formula which
      predicts lymph node metastasis by linear discriminant analysis. In addition, we
      prospectively validated this formula in another subset of 106 consecutive
      patients with EGC and compared the predicted with the actual pathological lymph
      node metastasis. RESULTS: Multivariate analyses revealed that independent
      factors, which affect lymph node metastasis for EGC, were lymphatic system
      invasion (p=0.00002, odds ratio 3.11) and venous system invasion (p=0.039, odds
      ratio 2.44). In addition, we developed the lymph node metastasis-predicting
      formula using these two factors by linear discriminant analysis. The formula is
      as follows: Y=0.12 * (venous system invasion: 0, 1, 2 or 3) + 0.19 * (lymphatic
      system invasion: 0, 1, 2, or 3) - 0.14. If Y>0, we judge that a patient with
      gastric cancer is susceptible lymph node metastasis. The result of this
      prospective study showed that the sensitivity and specificity rates were 70% and
      61.6%, respectively. CONCLUSION: We developed a formula which can predict lymph
      node metastasis using linear discriminant analysis. This formula seems useful in
      predicting for lymph node metastasis in patients with EGC.

PMID- 25075089
TI  - Proceedings of the 17th Annual Meeting of the Society of Biotherapeutic
      Approaches, Dec 7, 2013, Fukuoka, Japan.

PMID- 25075090
TI  - Novel treatment strategies for cancer and their tumor-targeting approaches using
      antibodies against tumor-associated antigens.
AB  - Novel treatment strategies for cancer that are based on a more detailed
      understanding over the tumor biology are based on the latest new technology and
      are expected to improve the current treatment outcome for patients with cancer.
      However, many of these strategies still have one common and critical problem,
      being their limited specificity for tumor cells. In this context, antibodies
      against tumor-associated antigens (TAAs) are used in several ways to increase the
      tumor specificity of these novel strategies. Firstly, photodynamic or sonodynamic
      therapy using anti-TAA antibodies conjugated with new sensitizers offers
      additional therapeutic approaches. Secondly, re-targeting of T-cell immunotherapy
      using an anti-TAA antibody fusion protein was shown to be useful for the success
      of cancer immunotherapy, because the down-regulation of HLA class I molecules in
      tumor tissues constitutes a major tumor escape mechanism associated with tumor
      specific cellular immunity. Thirdly, in oncolytic virotherapy, targeting viral
      vectors carrying cytolytic activity against tumor tissues by modifying the
      tropisms with anti-TAA antibodies is also very promising from a practical point
      of view. 

PMID- 25075091
TI  - The roles of ZFAT in thymocyte differentiation and homeostasis of peripheral
      naive T-cells.
AB  - ZFAT (zinc-finger gene in AITD susceptibility region), originally identified as a
      candidate susceptibility gene for autoimmune thyroid disease, has been reported
      to be involved in various cellular processes and several common diseases
      including multiple sclerosis. Recent studies revealed that mouse Zfat is a novel
      critical regulator for both thymocyte differentiation and peripheral T-cell
      homeostasis. Zfat deficiency at early thymocyte developmental stages results in
      the inhibition of the development of CD4(+)CD8(+) thymocytes with an impaired
      positive selection. Zfat deficiency in peripheral T-cells results in a reduction
      in the number of T-cells with decreased expression of the interleukin-7 receptor
      alpha (IL-7Ralpha) that is critical for T-cell homeostasis. In addition, T-cell
      antigen receptor stimulation-induced responses of Zfat-deficient T-cells are also
      impaired, with reduced IL-2Ralpha expression. This review highlights and
      discusses the roles of Zfat in thymocyte differentiation of T-cells and in the
      homeostasis of naive T-cells with recent work. 

PMID- 25075092
TI  - Usefulness of oral administration of lipopolysaccharide for disease prevention
      through the induction of priming in macrophages.
AB  - Many publications show that macrophages are closely involved in etiology of
      diseases, such as cancer, diabetes, arteriosclerosis, and Alzheimer's disease.
      Recent studies show that waste products (e.g. dead cells, denatured proteins,
      oxidized lipids, and advanced glycation end-products) are the real causative
      agents of lifestyle-associated diseases. From the standpoint of health
      maintenance, macrophages eliminate foreign objects and waste products from an
      animal's body and appear to be quite important for maintaining homeostasis. There
      are two stages of activation of macrophages: one is priming and the other is the
      triggering stage with cytokine secretion. The priming stage of macrophages is an
      ostensibly functional stage without characteristic morphological changes and
      secretion of cytokines, but it functionally promotes clearance of waste products.
      In this review, we discuss the usefulness of oral administration of
      lipopolysaccharide (LPS) as a macrophage-priming agent for prevention/treatment
      of several diseases, including cancer. Moreover, the oral administration of LPS
      is safe. These observations suggest that LPS may be considered a vitamin-like
      substance with therapeutic properties. 

PMID- 25075093
TI  - An NDT study of a boron tracedrug UTX-51 for glycated BSA as an AGE model.
AB  - BACKGROUND: Conventional therapies for diseases that are associated with protein
      aggregation typically prevent rather than clear protein aggregates. We have
      proposed neutron dynamic therapy (NDT) as a physical clearance therapy for
      protein aggregates. Advanced glycation end-products (AGEs), which are aggregated
      proteins, have been implicated in diabetes, Alzheimer's, and heart disease.
      Herein, we report the use of the boron tracedrug UTX-51, under thermal neutron
      irradiation, as an NDT for the targeted clearance of glycated bovine serum
      albumin (Gly-BSA), a model of AGEs. MATERIALS AND METHODS: Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis was performed to detect Gly-BSA decomposition
      by thermal neutron irradiation treated with UTX-51. RESULTS: The combination of
      UTX-51 with neutron irradiation showed a decrease in band intensity of Gly-BSA.
      CONCLUSION: We present our NDT strategy, which has been used for the targeted
      clearance of Gly-BSA, suggesting that NDT with boron tracedrugs can be used for
      the treatment of AGEs-related disease.

PMID- 25075094
TI  - An epithelial cell adhesion molecule- and CD3-bispecific antibody plus activated
      T-cells can eradicate chemoresistant cancer stem-like pancreatic carcinoma cells
      in vitro.
AB  - Cancer stem-like properties of various types of cancer, including pancreatic
      cancer, one of the most aggressive types, correlate with metastasis, invasion,
      and therapeutic resistance. More importantly, chemoresistance in cancer stem-like
      cells (CSLCs) is a critical problem for eradication of pancreatic cancer. Several
      cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM),
      are molecular targets on CSLCs of pancreatic carcinoma. In this study, we
      investigated whether catumaxomab, a clinical-grade bi-specific antibody that
      binds to both EpCAM on tumor cells and CD3 on T-cells, combined with activated T
      cells can eliminate chemoresistant pancreatic CSLCs in vitro. Firstly, we
      established a CSLC line (MU-PK1) from human pancreatic carcinoma cells derived
      from a patient with chemoresistant and disseminated pancreatic cancer. These
      CSLCs were almost completely resistant to gemcitabine-mediated cytotoxicity up to
      a concentration of 10 MUg/ml. The cells expressed high levels of CSLC markers
      (CD44 and EpCAM) and had significantly higher capacities for sphere formation,
      invasion, and aldehyde dehydrogenase-1 expression, which are associated with
      cancer stemness properties. We found that pre-treatment with catumaxomab and
      subsequent addition of interleukin-2/OKT3 activated autologous T-cells eliminated
      CSLCs during a short incubation period. Moreover, when MU-PK1 cells were cultured
      under hypoxic conditions, the CSLCs became more aggressive. However, the
      combination of cytokine-activated killer T-cells with catumaxomab successfully
      lysed almost all these cells. In conclusion, catumaxomab combined with activated
      T-cells may be a potent therapeutic modality to eradicate chemoresistant
      pancreatic CSLCs. 

PMID- 25075095
TI  - Investigation on the reaction conditions of Staphylococcus aureus sortase A for
      creating surface-modified liposomes as a drug-delivery system tool.
AB  - BACKGROUND/AIM: This study aimed to determine the preferred conditions for the
      transpeptidase reaction of sortase A from Staphylococcus aureus, for the purpose
      of creating functional liposomes useful for a drug-delivery system (DDS).
      MATERIALS AND METHODS: His-tagged recombinant sortase A with 59 amino acids
      deleted from the N-terminus (His-DeltaN59SrtA) was prepared using an Escherichia
      coli expression system. The pH dependency and sorting signal sequence dependency
      of the transpeptidase reaction of His-DeltaN59SrtA were analyzed by monitoring
      the transfer of model donor-substrates (i.e. His-tagged mutant green fluorescent
      proteins with a C-terminal LPxTG sorting signal) to model acceptor-beads with a
      GGGGGC peptide. In addition, using preferred conditions, the sortase A reaction
      was used to modify liposome surface. RESULTS AND DISCUSSION: The transpeptidase
      reaction of His-DeltaN59SrtA was enhanced under weakly acidic conditions.
      Transfer efficiency, based on sorting signal recognition by His-DeltaN59SrtA, was
      similar to or higher than that obtained using several substrates with amino acids
      other than Glu in the sorting signal position "x". Furthermore, liposomes
      containing GGGGGC peptide-linked dipalmitoylphosphatidylethanolamine were
      successfully modified using the preferred conditions for His-DeltaN59SrtA
      determined in this study. CONCLUSION: Preferred conditions for the transpeptidase
      reaction of His-DeltaN59SrtA, especially in a weakly acidic environment to
      enhance reaction, was established and successfully used to create functional
      liposomes applicable to DDS.

PMID- 25075096
TI  - NKG2D-directed cytokine-activated killer lymphocyte therapy combined with
      gemcitabine for patients with chemoresistant metastatic solid tumors.
AB  - Natural-killer group 2, member D (NKG2D) is an activating receptor found on
      activated natural killer cells and on activated T-cells, here termed cytokine
      activated killer (CAK) cells. NKG2D ligands are expressed on various human cancer
      types. Gemcitabine is an anticancer drug which is a less immune-destructive agent
      than others. Herein, we investigated the clinical efficacy and the underlying
      mechanisms of a combination of CAK cell infusion therapy and gemcitabine. Twenty
      three patients with disseminated carcinomas were treated with chemo-immunotherapy
      consisting of CAK cell infusion therapy following gemcitabine treatment. To
      investigate the underlying mechanisms by which CAK cells synergize with
      gemcitabine, we used enzyme-linked immunosorbent assay, Real-time reverse
      transcription polymerase chain reaction assay, calcein-release assay, and
      adherent target detachment assay. Using these assays we determined the NKG2D
      ligands such as major histocompatibility complex-class I-related chain (MIC)A/B
      expression in carcinoma cells and the level of cellular cytotoxicity generated by
      treatment with gemcitabine with/without CAK cells. The tumor responses differed
      among the patients (n=23). In vitro experiments revealed that MICA/B protein and
      mRNA expression were up-regulated in several carcinoma cell lines after
      gemcitabine treatment. Pre-treatment with gemcitabine and subsequent exposure to
      CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of
      soluble MICB in CAK cell-mediated cytotoxicity assay significantly reduced
      cytotoxicity. Our clinical results of gemcitabine-CAK combinatorial therapy
      demonstrated long-term stable disease despite chemoresistance. In conclusion, the
      combination of gemcitabine and CAK cells may have clinical therapeutic
      significance for pancreatic, hepato-biliary tract, and urothelial tract cancer.
      Our study shows that combining CAK therapy with gemcitabine can lead to
      successful treatment of metastatic cancer. 

PMID- 25075097
TI  - Multicolor analysis of cell surface marker of human leukemia cell lines using
      flow cytometry.
AB  - BACKGROUND: Leukemia cell lines are utilized as tools for molecular analysis.
      Their implementation in therapy will require standards for quality control,
      including appropriate selection criteria for functional analysis and efficacy
      determination. MATERIALS AND METHODS: Characteristics of six human leukemia cell
      lines -Kasumi-1, NB-4, MOLM-13, MV-4-11, K562, and Jurkat cells-were investigated
      using multiple color analysis of surface antigen expression and comparative
      analysis of gene expression. RESULTS: Differentiation states of Kasumi-1 and MOLM
      13 cells are colony-forming units-granulocyte/macrophage equivalent cells to
      myeloblasts with comparatively high Growth factor independent-1(GFI1) and
      Transcription factor PU.1 (PU.1) expression, respectively. NB4 and MV-4-11
      express high levels of CCAAT/enhancer-binding protein-alpha (CEBPalpha) and
      differentiate from myeloblasts to pro-monocytes and myeloblasts, respectively.
      K562 cells are colony-forming units-erythroid equivalent cells to erythroblasts,
      with the highest expression of GATA-binding factor 2 (GATA2), GATA1 and Friend of
      gata-1 (FOG1). Jurkat cells are pro-T to mature T-cells with the highest
      Neurogenic locus notch-1 homolog protein 1 (NOTCH1) expression. CONCLUSION: Our
      study gives a useful guideline of standards for appropriate usage of leukemia
      cell lines for examining novel targets in vitro.

PMID- 25075098
TI  - Resveratrol induces luminal apoptosis of human colorectal cancer HCT116 cells in
      three-dimensional culture.
AB  - BACKGROUND: We have previously reported the crucial roles of oncogenic Kirsten
      rat sarcoma viral oncogene homolog (KRAS) in inhibiting apoptosis and disrupting
      cell polarity via the regulation of phosphodiesterase 4 (PDE4) expression in
      human colorectal cancer HCT116 cells in three-dimensional cultures (3DC). Herein
      we evaluated the effects of resveratrol, a PDE4 inhibitor, on the luminal cavity
      formation and the induction of apoptosis in HCT116 cells. MATERIALS AND METHODS:
      Apoptosis was detected by immunofluorescence using confocal laser scanning
      microscopy with an antibody against cleaved caspase-3 in HCT116 cells treated
      with or without resveratrol in a two-dimensional culture (2DC) or 3DC. RESULTS:
      Resveratrol did not induce apoptosis of HCT116 cells in 2DC, whereas the number
      of apoptotic HCT116 cells increased after resveratrol treatment in 3DC, leading
      to formation of a luminal cavity. CONCLUSION: Resveratrol induced apoptosis of
      HCT116 cells in 3DC, resulting in the formation of a luminal cavity, probably by
      inhibiting PDE4 activity.

PMID- 25075099
TI  - A neutron dynamic therapy with a boron tracedrug UTX-51 using a compact neutron
      generator.
AB  - BACKGROUND/AIM: We are developing a neutron dynamic therapy (NDT) with boron
      tracedrugs for a new mechanical-clearance treatment of pathotoxic misfolded,
      aggregated, and self-propagating prion-associated disease proteins. We present a
      compact neutron generator-based NDT using a boron tracedrug UTX-51. Our NDT is
      based on the weak thermal neutron-bombarded destructive action of UTX-51 on
      bovine serum albumin (BSA) using the neutron beams produced from a compact
      inertial electrostatic confinement fusion (IECF) neutron generator. RESULTS: BSA
      as an NDT molecular target was subjected to thermal neutron irradiation for eight
      hours using a compact neutron generator. The sodium dodecyl sulfate
      polyacrylamide gel electrophoresis pattern showed no protein band when 2 nmoles
      of BSA were irradiated with more than 100 nmoles of UTX-51, while BSA was not
      affected when irradiated without UTX-51. CONCLUSION: For the first time, we have
      succeeded in the molecular destruction of a prion-disease model protein, BSA, by
      NDT with a boron tracedrug, UTX-51, using a compact neutron generator.

PMID- 25075100
TI  - Dok2 likely down-regulates Klf1 in mouse erythroleukemia cells.
AB  - BACKGROUND/AIM: Docking protein 2 (Dok2) is an adapter protein which is involved
      in hematopoiesis. However, it still remains unclear how Dok2 functions in
      regulation of transcription of hematopoietic genes. To address this issue, we
      knocked-down Dok2 mRNA in mouse erythroleukemia cells which highly express Dok2
      intrinsically. MATERIALS AND METHODS: Mouse erythroleukemia cells were
      transfected with Dok2 siRNA for 24 h and gene expression of erythroid
      differentiation-related genes, such as GATA binding protein 1 (Gata1), Kruppel
      like factor 1 (Klf1), alpha-globin and beta-globin were assessed by real-time
      polymerase chain reaction. RESULTS: Among the tested genes, expression of Klf1
      exhibited a 1.94-fold increase when compared to the control 24 h after
      transfection. Immunocytochemistry and chromatin immunoprecipitation assays
      revealed that Dok2 protein localizes in the nucleus and binds to the promoter
      region of Klf1 gene. CONCLUSION: Dok2 is able to control Klf1 expression by
      transcriptional regulation through directly binding to its promoter region.

PMID- 25075101
TI  - Minichromosome maintenance protein 7 is a risk factor for recurrence in patients
      with Dukes C colorectal cancer.
AB  - BACKGROUND: It has been hypothesized that minichromosome maintenance (MCM)
      proteins, which are replicative control factors, can be used to detect tumor
      proliferation. The aim of the present study was to investigate the expression of
      MCM in colorectal cancer tissues and correlate it to clinical outcomes. PATIENTS
      AND METHODS: The study included 145 patients with colorectal cancer who underwent
      curative surgery, from January 2002 until December 2004, at the Kurume University
      Hospital in Fukuoka, Japan. The median follow-up duration was 87 months. The
      expression of MCM7 in tissues was studied by immuno-histochemical staining. The
      labeling index (LI) of MCM7 was calculated by dividing the number of positively
      stained cells by the total number of cells counted. We divided samples into two
      groups: positive (MCM7 LI 76% or higher) and negative (MCM7 LI less than 76%).
      RESULTS: In patients with Dukes A and B, there were no significant differences in
      either overall survival (OS) or recurrence-free survival (RFS) between patents
      with MCM7-positive and those with MCM7-negative disease. On the other hand, in
      patients with Dukes C, there was significantly worse OS and RFS for patients with
      MCM7-positive compared to those with MCM7-negative disease. CONCLUSION: We found
      that the expression of MCM7 is an independent risk factor for RFS in patients
      with Dukes C colorectal cancer. Further studies are required to investigate the
      validity of MCM7 protein expression for its potential clinical use in colorectal
      cancer therapy and prognosis.

PMID- 25075102
TI  - A novel assay system for macrophage-activating factor activity using a human U937
      cell line.
AB  - BACKGROUND: Macrophages play important roles in antitumor immunity, and
      immunotherapy with the group-specific component protein-derived macrophage
      activating factor (GcMAF) has been reported to be effective in patients with
      various types of cancers. However, in macrophage research, it is important to
      properly evaluate macrophage activity. MATERIALS AND METHODS: U937 macrophages
      were induced by 12-O-tetradecanoyl-13-phorbolacetate (TPA). The phagocytic
      activity of macrophages was evaluated as the internalized beads ratio. The MAF
      activity was assessed at 30 min after MAF addition as the activation ratio.
      RESULTS: We established a novel assay for phagocytic activities using
      differentiated U937 macrophages. CONCLUSION: The novel protocol was simple and
      rapid and was sensitive for GcMAF. This protocol should be useful not only for
      basic studies, such as those on molecular mechanisms underlying macrophage
      activation, but also for clinical studies, such as assessment of GcMAF activity
      prior to clinical use.

PMID- 25075103
TI  - Evaluation of the sonosensitizing activities of 5-aminolevulinic acid and Sn(IV)
      chlorin e6 in tumor-bearing chick embryos.
AB  - BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA), precursors of protoporphyrin
      IX (PpIX), and Sn(IV) chlorin e6 (SnCe6) have been proposed as possible
      sonosensitizers for sonodynamic therapy of cancer. Therefore, we evaluated the
      pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in
      vivo by using the EMT6/KU tumor-bearing chick embryos. RESULTS: The concentration
      of PpIX in tumor and liver tissues and serum increased in a time-dependent manner
      after the i.v. administration of 5-ALA; PpIX concentrations reached their peak
      level after 5-7 h. The concentration of SnCe6 reached its maximum value in the
      tumor tissue and serum immediately after i.v. administration. The combined
      treatment of 5-ALA or SnCe6 with ultrasound irradiation showed a significant
      antitumor effect towards EMT6/KU solid tumors. CONCLUSION: We evaluated the
      pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in a
      chick embryo model and found that 5-ALA might be more suitable as a
      sonosensitizer than SnCe6.

PMID- 25075104
TI  - Case report: A breast cancer patient treated with GcMAF, sonodynamic therapy and
      hormone therapy.
AB  - BACKGROUND: Gc protein-derived macrophage-activating factor (GcMAF) occurs
      naturally in the human body. It has various functions, such as macrophage
      activation and antitumor activities. Recently, immunotherapy has become an
      attractive new strategy in the treatment of cancer. GcMAF-based immunotherapy can
      be combined with many other therapies. Sonodynamic therapy (SDT) using low
      intensity ultrasound is a novel therapeutic modality. Ultrasound has been
      demonstrated to activate a number of sonosensitive agents allowing for the
      possibility of non-invasive targeted treatment for both superficial and deep
      seated tumors. The current case study demonstrates that GcMAF and SDT can be used
      in combination with conventional therapies in patients with metastatic cancer,
      especially where treatment options are limited due to factors such as toxicity.
      This case study also suggests a new concept of cancer treatment using local
      destruction of cancer tissue, in this case conducted with SDT, to be used in
      combination with GcMAF immunotherapy as a systemic treatment.

PMID- 25075105
TI  - Efficacy and safety of irinotecan plus S-1 (IRIS) therapy to treat
      advanced/recurrent colorectal cancer.
AB  - BACKGROUND: 5-Fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX) therapy
      and 5-FU, leucovorin, and irinotecan (FOLFIRI) therapy are standard
      chemotherapies to treat advanced/recurrent colorectal cancer. However, these
      chemotherapies require continuous infusion of 5-FU for a prolonged time of 40 h
      or more, every two weeks. Accordingly, these chemotherapies require
      hospitalization and placement of a central venous catheter. Because of frequent
      catheterization, long-term use of these therapies potentially risks complications
      such as infection and thrombosis. In contrast, S-1 (tegaful, gimeracil, oteracil)
      combined with irinotecan (IRIS) therapy involves giving one drug orally and
      infusing the other for about two hours every two weeks, so placement of a central
      venous catheter is not necessary. The current study examined the efficacy and
      safety of IRIS therapy in 90 patients at this Hospital who underwent such therapy
      to treat advanced/recurrent colorectal cancer. PATIENTS AND METHODS: The study
      comprised 90 patients who underwent IRIS therapy to treat advanced/recurrent
      colorectal cancer from December 2004 to December 2011. RESULTS: The ratio of male
      to-female patients was 64:26. The mean age at the start of IRIS therapy was 64.5
      years, and patients underwent an average of 11 courses of therapy. The response
      rate to IRIS therapy was 14.8%, the disease control rate was 60.5%, and the
      overall survival time was 26.7 months. The incidence of adverse events was 70.0%,
      and the incidence of grade 3 or more severe adverse reactions was 17.8%.
      CONCLUSION: In comparison to the standard therapies of FOLFOX and FOLFIRI, IRIS
      therapy had a lower response rate but led to an equivalent overall survival time.
      IRIS therapy had a low incidence of serious adverse events and allowed patients
      to continue therapy on an out-patient basis. These findings indicate that IRIS
      therapy may be a useful form of chemotherapy to treat advanced/recurrent
      colorectal cancer.

PMID- 25075106
TI  - Prospective evaluation of safety of immune-cell therapy for patients with various
      types of advanced cancer.
AB  - Several types of immune-cell therapies, such as alphabeta T-cell, gammadelta T
      cell, and dendritic cell (DC) vaccine therapies, are clinically employed for
      cancer treatment. The safety of immune-cell therapy for the treatment of patients
      with malignancies should be maintained by continuous assessment of adverse
      events. In the present study, we surveyed the adverse events associated with
      immune-cell therapy using large-scale prospective data and analyzed the side
      effect profiles. For the assessment of adverse events associated with immune-cell
      therapy, we evaluated 771 treatment profiles (484 for alphabeta T-cell therapy,
      58 for gammadelta T-cell therapy, 206 for DC vaccine therapy, and 23 for
      concurrent therapy with alphabeta T-cells and DC vaccines) from 144 patients with
      various malignancies. For the assessment of fever, fatigue, and itching, each of
      these adverse events was found to be grade 1 or 2 in most of the treated
      patients, except for one patient who had grade 3 itching. It was suggested that
      alphabeta T-cell therapy could elicit a more rapid and direct immune reaction in
      patients than DC vaccine therapy, as shown by the earlier development of fever
      and higher incidence rate of fatigue. It was found that grade 1 or 2 reaction at
      the injection site developed in 10.2% of the patients injected with DC vaccines.
      Most of the grade 3 non-hematological and hematological adverse events were
      associated with disease progression or side-effects of chemotherapy, and were not
      considered to be related to immune-cell therapy. In conclusion, immune-cell
      therapy, such as alphabeta T-cell, gammadelta T-cell, or DC vaccine therapy, was
      well-tolerated for cancer treatment. 

PMID- 25075107
TI  - Expression of chemotaxis- and angiogenesis-related factors in human monocytes
      following interaction with colon cancer cells is suppressed by low-dose
      lipopolysaccharide.
AB  - BACKGROUND: We have previously reported that mRNA expression of chemotaxis- and
      angiogenesis-related factors in human monocytes increased following interaction
      with colon cancer cells. Recently, it was also reported that mRNA expression of
      the chemotaxis-related factor, monocyte chemotactic protein (MCP)-1, in mouse
      macrophages following treatment with low-dose lipopolysaccharide (LPS) was
      significantly lower compared to that following treatment with high-dose LPS, and
      that low-dose LPS failed to activate the classical nuclear factor (NF)-kappaB
      pathway. In the present study, we examined changes in mRNA expression of
      chemotaxis- and angiogenesis-related factors in human monocytes following low
      dose LPS treatment and subsequent interaction with colon cancer cells. MATERIALS
      AND METHODS: The human monocyte cell line THP-1 was treated with LPS and
      subsequently co-cultured with the human colon cancer cell line DLD-1. mRNA
      expression was analyzed by quantitative real-time PCR. RESULTS: mRNA expression
      of MCP-1, vascular endothelial growth factor (VEGF)-A, tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta and IL-8 in THP-1 cells treated with low-dose
      LPS (100 pg/ml) decreased compared to untreated THP-1 cells after five days of co
      culture with DLD-1 cells. CONCLUSION: mRNA expression of chemotaxis- and
      angiogenesis-related factors in human monocytes following interaction with colon
      cancer cells is suppressed by prior treatment with low-dose LPS. Thus, low-dose
      LPS treatment of human monocytes may be useful for prevention and therapy of
      colon cancer.

PMID- 25075108
TI  - Pre-clinical study of BK-UM, a novel inhibitor of HB-EGF, for ovarian cancer
      therapy.
AB  - BACKGROUND/AIM: Heparin-binding epidermal growth factor-like growth factor (HB
      EGF), a member of the epidermal growth factor family, is a target for ovarian
      cancer therapy. The present study investigated the administration schedule of BK
      UM, an anticancer agent targeting HB-EGF. MATERIALS AND METHODS: The ovarian
      cancer cell line, RMG-I, was injected subcutaneously into five-week-old female
      nude mice. The BK-UM was administered intraperitoneally, using three
      administration schedules with different doses. The tumor volume was calculated
      every week. Statistical significance was assessed using the Mann-Whitney U-test.
      RESULTS: At doses >0.1 mg/kg, BK-UM displayed significant antitumor effects,
      although the antitumor effects and body weights of mice did not significantly
      differ by dose or by three different administration schedules. At a dose <0.1
      mg/kg, however, BK-UM had little inhibitory effect on tumor growth. CONCLUSION:
      Daily administration of BK-UM, which has a potentially dose-dependent antitumor
      effect, may be the optimal schedule for clinical application.

PMID- 25075109
TI  - Radiosensitivity uncertainty evaluation for the in vitro biophysical modeling of
      EMT6 cells.
AB  - BACKGROUND/AIM: The aims of this study were to evaluate the cell survival
      uncertainty distribution of radiation and to assess the accuracy of predictions
      of tumor response by using three different in vitro experimental cell cultures
      with radiosensitizers (including etanidazole). MATERIALS AND METHODS: Using EMT6
      cells and X-rays, the cell survival fraction was obtained from 15, 34, and 21
      different experiments under normoxic, hypoxic, and hypoxic-plus-radiosensitizer
      culture, respectively. RESULTS: The alpha coefficients were 0.257 +/- 0.188,
      0.078 +/- 0.080, and 0.182 +/- 0.116 Gy(-1), respectively. The beta coefficients
      were 0.0159 +/- 0.0208, 0.0076 +/- 0.0113, and 0.0062 +/- 0.0077 Gy(-2),
      respectively. The alpha coefficient and the dose that killed half of the
      clonogens population (D50) were significantly different between normoxic cell and
      hypoxic cell cultures (p<0.01), respectively. The use of radiosensitizers under
      hypoxic conditions improved radiosensitivity. CONCLUSION: Our results suggest
      that parameter value distributions are required for biophysical modeling of
      applications for radiotherapy.

PMID- 25075110
TI  - Molecular analysis of Streptococcus anginosus-derived SagA peptides.
AB  - BACKGROUND: SagA1 and SagA2 molecules produced from beta-hemolytic Streptococcus
      anginosus subsp. anginosus are composed of a leader peptide and a propeptide, and
      their mature form has hemolytic activity as a well-known Streptococcal peptide
      toxin, streptolysin. The function of these SagA molecules is thought to be
      dependent on intra-molecular heterocycle formation. In this study, we examined
      the heterocycle-involved molecular features of SagA1, SagA2, and S. pyogenes SagA
      (SPySagA), focusing on their heterocycle formation. MATERIALS AND METHODS:
      Molecular models of SagA1, SagA2, and SPySagA were constructed using a molecular
      modeling technique. Molecular dynamics and molecular mechanic analyses of the
      modeled SagA molecules were performed to obtain their energy profiles. RESULTS:
      Total energy of the modeled SagA1, SagA2, and SPySagA decreased with heterocycle
      formation, and the border between the leader peptide and propeptide was clearly
      observed after heterocycle formation. CONCLUSION: The flexibility of SagA
      molecules was changed by intramolecular heterocycle formation, and their function
      (e.g. hemolytic activity) seems to be regulated by structural transition with
      heterocycle formation.

PMID- 25075111
TI  - Benefit of lateral lymph node dissection for rectal cancer: long-term analysis of
      944 cases undergoing surgery at a single center (1975-2004).
AB  - BACKGROUND: Pelvic sidewall dissection (PSD) has the potential to decrease local
      recurrence so that PSD may be an effective strategy for lower rectal cancer.
      Therefore, it is important to investigate the validity of PSD for its potential
      clinical use in lower rectal cancer therapy and prognosis. PATIENTS AND METHODS:
      The present study included all 994 patients with rectal cancer who underwent
      curative surgery from January 1975 until December 2004 at the Kurume University
      Hospital in Fukuoka. The patients were analyzed to determine whether lateral
      lymph node (LLN) metastasis was correlated with clinicopathological factors, and
      in the overall study population, 5-year disease-free survival (DFS), and the 5
      years overall survival (OS) were analyzed. RESULTS: In patients with stage 3a
      cancer there was no significant difference in DFS between those with and without
      PSD. On the other hand, in patients with stage 3b DFS was significantly worse
      with PSD than without PSD. We analyzed the DFS and OS according to the number of
      lymph nodes with LLN-positive metastasis. Those with fewer than three positive
      lymph nodes had a significantly better DFS and OS compared to those with three or
      more. Moreover, those with only ore region of positive lymph node had a
      significantly better DFS and OS compared to those with two or more regions.
      CONCLUSION: These results demonstrate that PSD was of benefit for prognosis for
      patients with fewer than three positive lymph nodes, those limited to within only
      one region and LLN metastasis only.

PMID- 25075112
TI  - Child death overview panel: an intensive care retrieval perspective.

PMID- 25075113
TI  - Circleator: flexible circular visualization of genome-associated data with
      BioPerl and SVG.
AB  - SUMMARY: Circleator is a Perl application that generates circular figures of
      genome-associated data. It leverages BioPerl to support standard annotation and
      sequence file formats and produces publication-quality SVG output. It is designed
      to be both flexible and easy to use. It includes a library of circular track
      types and predefined configuration files for common use-cases, including. (i)
      visualizing gene annotation and DNA sequence data from a GenBank flat file, (ii)
      displaying patterns of gene conservation in related microbial strains, (iii)
      showing Single Nucleotide Polymorphisms (SNPs) and indels relative to a reference
      genome and gene set and (iv) viewing RNA-Seq plots. AVAILABILITY AND
      IMPLEMENTATION: Circleator is freely available under the Artistic License 2.0
      from http://jonathancrabtree.github.io/Circleator/ and is integrated with the
      CloVR cloud-based sequence analysis Virtual Machine (VM), which can be downloaded
      from http://clovr.org or run on Amazon EC2.

PMID- 25075114
TI  - Metabomxtr: an R package for mixture-model analysis of non-targeted metabolomics
      data.
AB  - SUMMARY: Non-targeted metabolomics technologies often yield data in which
      abundance for any given metabolite is observed and quantified for some samples
      and reported as missing for other samples. Apparent missingness can be due to
      true absence of the metabolite in the sample or presence at a level below
      detectability. Mixture-model analysis can formally account for metabolite
      'missingness' due to absence or undetectability, but software for this type of
      analysis in the high-throughput setting is limited. The R package metabomxtr has
      been developed to facilitate mixture-model analysis of non-targeted metabolomics
      data in which only a portion of samples have quantifiable abundance for certain
      metabolites. AVAILABILITY AND IMPLEMENTATION: metabomxtr is available through
      Bioconductor. It is released under the GPL-2 license. CONTACT:
      dscholtens@northwestern.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25075115
TI  - Retro: concept-based clustering of biomedical topical sets.
AB  - MOTIVATION: Clustering methods can be useful for automatically grouping documents
      into meaningful clusters, improving human comprehension of a document collection.
      Although there are clustering algorithms that can achieve the goal for relatively
      large document collections, they do not always work well for small and homogenous
      datasets. METHODS: In this article, we present Retro-a novel clustering algorithm
      that extracts meaningful clusters along with concise and descriptive titles from
      small and homogenous document collections. Unlike common clustering approaches,
      our algorithm predicts cluster titles before clustering. It relies on the
      hypergeometric distribution model to discover key phrases, and generates
      candidate clusters by assigning documents to these phrases. Further, the
      statistical significance of candidate clusters is tested using supervised
      learning methods, and a multiple testing correction technique is used to control
      the overall quality of clustering. RESULTS: We test our system on five disease
      datasets from OMIM((r)) and evaluate the results based on MeSH((r)) term
      assignments. We further compare our method with several baseline and state-of-the
      art methods, including K-means, expectation maximization, latent Dirichlet
      allocation-based clustering, Lingo, OPTIMSRC and adapted GK-means. The
      experimental results on the 20-Newsgroup and ODP-239 collections demonstrate that
      our method is successful at extracting significant clusters and is superior to
      existing methods in terms of quality of clusters. Finally, we apply our system to
      a collection of 6248 topical sets from the HomoloGene((r)) database, a resource
      in PubMed((r)). Empirical evaluation confirms the method is useful for small
      homogenous datasets in producing meaningful clusters with descriptive titles.
      AVAILABILITY AND IMPLEMENTATION: A web-based demonstration of the algorithm
      applied to a collection of sets from the HomoloGene database is available at
      http://www.ncbi.nlm.nih.gov/CBBresearch/Wilbur/IRET/CLUSTERING_HOMOLOGENE/index.h
      ml. CONTACT: lana.yeganova@nih.gov SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 25075116
TI  - Trowel: a fast and accurate error correction module for Illumina sequencing
      reads.
AB  - MOTIVATION: The ability to accurately read the order of nucleotides in DNA and
      RNA is fundamental for modern biology. Errors in next-generation sequencing can
      lead to many artifacts, from erroneous genome assemblies to mistaken inferences
      about RNA editing. Uneven coverage in datasets also contributes to false
      corrections. RESULT: We introduce Trowel, a massively parallelized and highly
      efficient error correction module for Illumina read data. Trowel both corrects
      erroneous base calls and boosts base qualities based on the k-mer spectrum. With
      high-quality k-mers and relevant base information, Trowel achieves high accuracy
      for different short read sequencing applications.The latency in the data path has
      been significantly reduced because of efficient data access and data structures.
      In performance evaluations, Trowel was highly competitive with other tools
      regardless of coverage, genome size read length and fragment size. AVAILABILITY
      AND IMPLEMENTATION: Trowel is written in C++ and is provided under the General
      Public License v3.0 (GPLv3). It is available at http://trowel-ec.sourceforge.net.
      CONTACT: euncheon.lim@tue.mpg.de or weigel@tue.mpg.de SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 25075117
TI  - Greater power and computational efficiency for kernel-based association testing
      of sets of genetic variants.
AB  - MOTIVATION: Set-based variance component tests have been identified as a way to
      increase power in association studies by aggregating weak individual effects.
      However, the choice of test statistic has been largely ignored even though it may
      play an important role in obtaining optimal power. We compared a standard
      statistical test-a score test-with a recently developed likelihood ratio (LR)
      test. Further, when correction for hidden structure is needed, or gene-gene
      interactions are sought, state-of-the art algorithms for both the score and LR
      tests can be computationally impractical. Thus we develop new computationally
      efficient methods. RESULTS: After reviewing theoretical differences in
      performance between the score and LR tests, we find empirically on real data that
      the LR test generally has more power. In particular, on 15 of 17 real datasets,
      the LR test yielded at least as many associations as the score test-up to 23 more
      associations-whereas the score test yielded at most one more association than the
      LR test in the two remaining datasets. On synthetic data, we find that the LR
      test yielded up to 12% more associations, consistent with our results on real
      data, but also observe a regime of extremely small signal where the score test
      yielded up to 25% more associations than the LR test, consistent with theory.
      Finally, our computational speedups now enable (i) efficient LR testing when the
      background kernel is full rank, and (ii) efficient score testing when the
      background kernel changes with each test, as for gene-gene interaction tests. The
      latter yielded a factor of 2000 speedup on a cohort of size 13 500. AVAILABILITY:
      Software available at http://research.microsoft.com/en
      us/um/redmond/projects/MSCompBio/Fastlmm/. CONTACT: heckerma@microsoft.com
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25075118
TI  - FARVAT: a family-based rare variant association test.
AB  - MOTIVATION: Individuals in each family are genetically more homogeneous than
      unrelated individuals, and family-based designs are often recommended for the
      analysis of rare variants. However, despite the importance of family-based
      samples analysis, few statistical methods for rare variant association analysis
      are available. RESULTS: In this report, we propose a FAmily-based Rare Variant
      Association Test (FARVAT). FARVAT is based on the quasi-likelihood of whole
      families, and is statistically and computationally efficient for the extended
      families. FARVAT assumed that families were ascertained with the disease status
      of family members, and incorporation of the estimated genetic relationship matrix
      to the proposed method provided robustness under the presence of the population
      substructure. Depending on the choice of working matrix, our method could be a
      burden test or a variance component test, and could be extended to the SKAT-O
      type statistic. FARVAT was implemented in C++, and application of the proposed
      method to schizophrenia data and simulated data for GAW17 illustrated its
      practical importance. AVAILABILITY: The software calculates various statistics
      for the analysis of related samples, and it is freely downloadable from
      http://healthstats.snu.ac.kr/software/farvat. CONTACT: won1@snu.ac.kr or
      tspark@stats.snu.ac.kr SUPPLEMENTARY INFORMATION: supplementary data are
      available at Bioinformatics online.

PMID- 25075119
TI  - BitPAl: a bit-parallel, general integer-scoring sequence alignment algorithm.
AB  - MOTIVATION: Mapping of high-throughput sequencing data and other bulk sequence
      comparison applications have motivated a search for high-efficiency sequence
      alignment algorithms. The bit-parallel approach represents individual cells in an
      alignment scoring matrix as bits in computer words and emulates the calculation
      of scores by a series of logic operations composed of AND, OR, XOR, complement,
      shift and addition. Bit-parallelism has been successfully applied to the longest
      common subsequence (LCS) and edit-distance problems, producing fast algorithms in
      practice. RESULTS: We have developed BitPAl, a bit-parallel algorithm for
      general, integer-scoring global alignment. Integer-scoring schemes assign integer
      weights for match, mismatch and insertion/deletion. The BitPAl method uses
      structural properties in the relationship between adjacent scores in the scoring
      matrix to construct classes of efficient algorithms, each designed for a
      particular set of weights. In timed tests, we show that BitPAl runs 7-25 times
      faster than a standard iterative algorithm. AVAILABILITY AND IMPLEMENTATION:
      Source code is freely available for download at
      http://lobstah.bu.edu/BitPAl/BitPAl.html. BitPAl is implemented in C and runs on
      all major operating systems. CONTACT: jloving@bu.edu or yhernand@bu.edu or
      gbenson@bu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 25075120
TI  - NetPathMiner: R/Bioconductor package for network path mining through gene
      expression.
AB  - NetPathMiner is a general framework for mining, from genome-scale networks, paths
      that are related to specific experimental conditions. NetPathMiner interfaces
      with various input formats including KGML, SBML and BioPAX files and allows for
      manipulation of networks in three different forms: metabolic, reaction and gene
      representations. NetPathMiner ranks the obtained paths and applies Markov model
      based clustering and classification methods to the ranked paths for easy
      interpretation. NetPathMiner also provides static and interactive visualizations
      of networks and paths to aid manual investigation. AVAILABILITY: The package is
      available through Bioconductor and from Github at
      http://github.com/ahmohamed/NetPathMiner.

PMID- 25075121
TI  - Ranibizumab in retinal vein occlusion: treatment recommendations by an expert
      panel.
AB  - Retinal vein occlusion (RVO) is a common cause of retinal vascular disease,
      resulting in potentially irreversible loss of vision despite the existence of
      several therapeutic options. The humanised monoclonal antibody fragment
      ranibizumab binds to and inhibits vascular endothelial growth factor, a key
      driver of macular oedema in RVO. In 2010, ranibizumab was approved in the USA for
      the treatment of macular oedema in RVO and, in 2011, ranibizumab was approved in
      the European Union for the treatment of visual impairment caused by macular
      oedema secondary to RVO in branch and central RVO. Ranibizumab provides an
      additional therapeutic option for this complex disease: an option that was not
      fully considered during the preparation of current international guidelines. An
      expert panel was convened to critically evaluate the evidence for treatment with
      ranibizumab in patients with visual impairment caused by macular oedema secondary
      to RVO and to develop treatment recommendations, with the aim of assisting
      physicians to optimise patient treatment. 

PMID- 25075122
TI  - Clinical features and management of cytomegalovirus corneal endotheliitis:
      analysis of 106 cases from the Japan corneal endotheliitis study.
AB  - AIMS: The purpose of this study is to elucidate the clinical manifestations and
      the current treatment status of cytomegalovirus (CMV) endotheliitis via a large
      case series obtained from a national survey conducted in Japan. METHODS: The
      Japan Corneal Endotheliitis Study Group proposed diagnostic criteria for CMV
      endotheliitis based on a viral examination by PCR of aqueous humour, in
      combination with clinical manifestations. A national survey was then
      retrospectively conducted among 1160 members of the Japan Cornea Society. The
      study reviewed the patient profiles, clinical manifestations, and treatment
      modalities of individuals who met the diagnostic criteria for CMV endotheliitis.
      RESULTS: The study included 109 eyes of 106 patients. Mean patient age was 66.9+/
      10.9 years (85 males (80.2%), 21 females (19.8%)). Patients were commonly
      diagnosed with anterior uveitis and ocular hypertension prior to confirmation of
      CMV endotheliitis. Coin-shaped lesions were observed in 70.6%, and linear keratic
      precipitates in 8.3% of the patients, respectively. 95% of cases were treated
      with anti-CMV drugs. CONCLUSIONS: CMV endotheliitis is most common in middle-aged
      and elderly men. CMV endotheliitis should be suspected when patients present with
      corneal endotheliitis involving coin-shaped lesions accompanied by anterior
      uveitis and ocular hypertension.

PMID- 25075123
TI  - CFI-rs7356506 is a genetic protective factor for acute anterior uveitis in
      Chinese patients.
AB  - BACKGROUND: Complement Factor I (CFI) and the CD46 complement regulator (CD46)
      play an important role in the complement activation pathways, which is known to
      affect the development of uveitis. The present study was performed to investigate
      the association of the CFI and CD46 genes with acute anterior uveitis (AAU).
      METHODS: A total of 600 subjects (300 patients with AAU and 300 healthy controls)
      were recruited for this case-control study. Six CFI single nucleotide
      polymorphisms (SNP) (rs7356506, rs10029485, rs11726949, rs12512308, rs7438961,
      rs998538) and four CD46 SNPs (rs12138764, rs2466571, rs2796278, rs7545126) were
      genotyped using Sequenom MassARRAY technology. Allele and genotype frequencies
      were compared between patients and controls using the chi(2) test. Analyses were
      stratified for gender, human leukocyte antigen (HLA)-B27, and ankylosing
      spondylitis status. RESULTS: Rs7356506 in the CFI gene was found to be protective
      against AAU. There was a significant increase in the frequency of the A allele
      (p=0.003, pc=0.03, OR=0.684, CI 0.534 to 0.876) and AA homozygosity (p=0.004,
      pc=0.04, OR=0.624, CI 0.452 to 0.862) in AAU patients as compared to controls.
      Stratified analysis, according to gender and HLA-B27 status for AAU, also
      revealed the association with CFI-rs7356506. None of the tested SNPs of CD46 were
      associated with AAU. CONCLUSIONS: This study has revealed a significant
      association between AAU and CFI-rs7356506, suggesting that CFI is involved in the
      pathogenesis of AAU, and that its influence on AAU may differ depending on gender
      and HLA-B27 status.

PMID- 25075124
TI  - Predicting proliferative vitreoretinopathy: temporal and external validation of
      models based on genetic and clinical variables.
AB  - PURPOSE: To validate three models for predicting proliferative vitreoretinopathy
      (PVR) based on the analysis of genotypic data and relevant clinical
      characteristics. METHODS: The validation series consisted of data from 546
      patients operated on from primary rhegmatogenous retinal detachment (RRD) coming
      from centres in the Netherlands, Portugal, Spain and the UK. Temporal and
      geographical validation was performed. The discrimination capability of each
      model was analysed and compared with the original series, using a receiver
      operating curve. Then, clinical variables were combined in order to improve the
      predictive capability. A risk reclassification analysis was performed with and
      without each one of the variables. Reclassification of patients was compared and
      models were readjusted in the original series. Readjusted models were further
      validated. RESULTS: One of the models showed good predictability in the temporal
      sample as well as in the original series (area under the curve (AUC)
      original=0.7352; AUC temporal=0.6457, 95% CI 50.17 to 78.97). When clinical
      variables were included, only pre-existent PVR improves the predictability of
      this model in the validation series (temporal and geographical samples) (AUC
      original=0.7940 vs AUC temporal=0.7744 and AUC geographical=0.7152). The other
      models showed acceptable AUC values when clinical variables were included
      although they were less accurate than in the original series. CONCLUSIONS:
      Genetic profiling of patients with RRD can improve the predictability of PVR in
      addition to the well-known clinical biomarkers. This validated formula could be a
      new tool in our current clinical practice in order to identify those patients at
      high risk of developing PVR.

PMID- 25075125
TI  - BMP type II receptors have redundant roles in the regulation of hepatic hepcidin
      gene expression and iron metabolism.
AB  - Expression of hepcidin, the hepatic hormone controlling iron homeostasis, is
      regulated by bone morphogenetic protein (BMP) signaling. We sought to identify
      which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is
      responsible for regulating hepcidin gene expression. We studied Bmpr2
      heterozygous mice (Bmpr2(+/-)), mice with hepatocyte-specific deficiency of
      BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes
      lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum
      hepcidin and iron levels, and tissue iron levels did not differ in wild-type
      mice, Bmpr2(+/-) mice, and mice in which either BMPR2 or ActR2a was deficient.
      Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene
      expression and serum hepcidin levels leading to severe iron overload. Iron
      injection increased hepatic hepcidin mRNA levels in mice deficient in either
      BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In
      addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and
      ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression.
      These results suggest that BMP type II receptors, BMPR2 and ActR2a, have
      redundant roles in the regulation of hepatic hepcidin gene expression and iron
      metabolism. 

PMID- 25075126
TI  - Acid sphingomyelinase is activated in sickle cell erythrocytes and contributes to
      inflammatory microparticle generation in SCD.
AB  - Sphingolipids are a class of lipids containing a backbone of sphingoid bases that
      can be produced de novo through the reaction of palmitate and serine and further
      metabolized through the activity of various enzymes to produce intermediates with
      diverse roles in cellular processes and signal transduction. One of these
      intermediates, sphingosine 1-phosphate (S1P), is stored at high concentrations (1
      MUM) in red blood cells (RBCs) and directs a wide array of cellular processes
      mediated by 5 known G-protein coupled receptors (S1P1-S1P5). In this study, we
      show that RBC membrane alterations in sickle cell disease enhance the activation
      acid sphingomyelinase by 13%, resulting in increased production and storage of
      sphingosine (2.6-fold) and S1P (3.5-fold). We also show that acid
      sphingomyelinase enhances RBC-derived microparticle (MP) generation. These MPs
      are internalized by myeloid cells and promote proinflammatory cytokine secretion
      and endothelial cell adhesion, suggesting that potential crosstalk between
      circulating inflammatory cells and MPs may contribute to the inflammation-rooted
      pathogenesis of the disease. Treatment with amitriptyline reduces MP generation
      in vitro and in vivo and might be used to mitigate inflammatory processes in
      sickle cell disease. 

PMID- 25075130
TI  - Mortality as a measure of quality of care in infants with congenital
      cardiovascular malformations following surgery.
AB  - INTRODUCTION: Mortality has traditionally been perceived as a straightforward
      measure of outcome and has been used to evaluate surgical performance. In the
      rapidly developing arena of paediatric cardiac surgery, the insightful analysis
      of mortality figures is challenging. SOURCES OF DATA: This report discusses the
      issues involved when mortality is used as a marker for surgical outcome,
      referring to national and international audit and research data. AREAS OF
      AGREEMENT: Mortality is an important variable and should be transparently
      defined, reported and monitored. AREAS OF CONTROVERSY: Definitions of mortality,
      assessments of risk and interpretations of reported statistics all have
      limitations that must be recognized. GROWING POINTS: Traditional use of raw early
      mortality as a simplistic indicator of outcome and performance is evolving to
      include risk-adjusted mortality, longer-term survival, reinterventions and
      complications. AREAS TIMELY FOR DEVELOPING RESEARCH: As the vast majority of
      children undergoing cardiac surgery now survive beyond 30 days, the focus for
      measures of quality is shifting towards morbidity.

PMID- 25075133
TI  - Moral Status and the Wrongness of Paternalism.
AB  - In this paper, I consider the view that paternalism is wrong when it demeans or
      diminishes the paternalizee's moral status (the Moral Status Argument). I argue
      that we should reject the Moral Status Argument because it is both too narrow and
      too broad. It is too narrow because it cannot account for the wrongness of some
      of the most objectionable paternalistic interventions, namely strong
      paternalistic interventions. It is too broad because it is unable to distinguish
      between wrongful paternalistic acts that are plausibly considered more wrong than
      other wrongful paternalistic acts.

PMID- 25075134
TI  - Dum spiro, spero.

PMID- 25075128
TI  - The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and
      clinical activity in multiple myeloma.
AB  - The PI3K/AKT pathway is constitutively active in hematologic malignancies,
      providing proliferative and antiapoptotic signals and possibly contributing to
      drug resistance. We conducted an open-label phase 1 study to evaluate the maximum
      tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of
      afuresertib-an oral AKT inhibitor-in patients with advanced hematologic
      malignancies. Seventy-three patients were treated at doses ranging from 25 to 150
      mg per day. The MTD was established at 125 mg per day because of 2 dose-limiting
      toxicities in the 150-mg cohort (liver function test abnormalities). The most
      frequent adverse events were nausea (35.6%), diarrhea (32.9%), and dyspepsia
      (24.7%). Maximum plasma concentrations and area under the plasma concentration
      time curves from time 0 to 24 hours were generally dose proportional at > 75-mg
      doses; the median time to peak plasma concentrations was 1.5 to 2.5 hours post
      dose, with a half-life of approximately 1.7 days. Three multiple myeloma patients
      attained partial responses; an additional 3 attained minimal responses. Clinical
      activity was also observed in non-Hodgkin lymphoma, Langerhan's cell
      histiocytosis, and Hodgkin disease. Single-agent afuresertib showed a favorable
      safety profile and demonstrated clinical activity against hematologic
      malignancies, including multiple myeloma.

PMID- 25075127
TI  - Paired immunoglobulin-like receptor B regulates platelet activation.
AB  - Murine paired immunoglobulin-like receptors B (PIRB), as the ortholog of human
      leukocyte immunoglobulin-like receptor B2 (LILRB2), is involved in a variety of
      biological functions. Here, we found that PIRB and LILRB2 were expressed in mouse
      and human platelets, respectively. PIRB intracellular domain deletion (PIRB-TM)
      mice had thrombocythemia and significantly higher proportions of megakaryocytes
      in bone marrow. Agonist-induced aggregation and spreading on immobilized
      fibrinogen were facilitated in PIRB-TM platelets. The rate of clot retraction in
      platelet-rich plasma containing PIRB-TM platelets was also increased.
      Characterization of signaling confirmed that PIRB associated with phosphatases
      Shp1/2 in platelets. The phosphorylation of Shp1/2 was significantly
      downregulated in PIRB-TM platelets stimulated with collagen-related peptide (CRP)
      or on spreading. The results further revealed that the phosphorylation levels of
      the linker for activation of T cells, SH2 domain-containing leukocyte protein of
      76kDa, and phospholipase C were enhanced in PIRB-TM platelets stimulated with
      CRP. The phosphorylation levels of FAK Y397 and integrin beta3 Y759 were also
      enhanced in PIRB-TM platelet spread on fibrinogen. The PIRB/LILRB2 ligand
      angiopoietin-like-protein 2 (ANGPTL2) was expressed and stored in platelet alpha
      granules. ANGPTL2 inhibited agonist-induced platelet aggregation and spreading on
      fibrinogen. The data presented here reveal that PIRB and its ligand ANGPTL2
      possess an antithrombotic function by suppressing collagen receptor glycoprotein
      VI and integrin alphaIIbbeta3-mediated signaling. 

PMID- 25075129
TI  - Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in
      XLF/Cernunnos deficiency.
AB  - XRCC4-like factor (XLF/Cernunnos) is a component of the nonhomologous end-joining
      (NHEJ) pathway of double-strand DNA break repair. XLF-deficient patients develop
      a severe progressive lymphocytopenia. Although NHEJ is required for V(D)J
      recombination and lymphocyte development, XLF-deficient mice have normal V(D)J
      recombination, highlighting the need for an alternative mechanism for the
      lymphocytopenia. Here, we report that XLF-deficient mice recapitulate the age
      dependent lymphocytopenia of patients. We show that XLF deficiency leads to
      premature aging of hematopoietic stem cells (HSCs), measured by decreased
      functional capacity in transplantation assays, preferential myeloid
      reconstitution, and reduced self-renewal at a young age. We propose that
      premature aging of HSCs, together with previously reported defects in class
      switch recombination and memory immune response, underlies the progressive and
      severe lymphocytopenia in XLF-deficient patients in the absence of measurable
      V(D)J recombination defects. 

PMID- 25075135
TI  - Emergency Medicine in the RVH and the challenges it faces from a clinician's
      perspective.

PMID- 25075136
TI  - Hereditary Gigantism-the biblical giant Goliath and his brothers.
AB  - The biblical giant Goliath has an identifiable family tree suggestive of
      autosomal dominant inheritance. We suggest that he had a hereditary pituitary
      disorder possibly due to the AIP gene, causing early onset and familial
      acromegaly or gigantism. We comment on the evidence within the scriptures for his
      other relatives including a relative with six digits and speculate on possible
      causes of the six digits. Recognition of a hereditary pituitary disorder in the
      biblical Goliath and his family sheds additional information on his and other
      family members' battles with David and his relatives. 

PMID- 25075137
TI  - Adrenal sarcomatoid carcinoma: a case report and review of the literature.
AB  - Adrenocortical sarcomatoid carcinoma (ASC) is an extremely rare variant of
      adrenocortical carcinoma (ACC). Its relative rarity and its characteristic
      histological pattern of both epithelioid and sarcomatoid components may pose
      diagnostic challenges which influence treatment. Here, we report a case of ASC in
      a 58 year-old man presenting with increasing abdominal pain and associated
      abdominal bloating with a large right adrenal mass detected by computed
      tomographic scan (CT). To our knowledge, only eleven prior cases of ASC have been
      reported in the literature. Here, we discuss the clinical, radiological and
      histopathological findings in our case, review the literature on ASCs and offer
      opinion on best management. 

PMID- 25075138
TI  - Diagnostic Lumbar Puncture.
AB  - Diagnostic Lumbar Puncture is one of the most commonly performed invasive tests
      in clinical medicine. Evaluation of an acute headache and investigation of
      inflammatory or infectious disease of the nervous system are the most common
      indications. Serious complications are rare, and correct technique will minimise
      diagnostic error and maximise patient comfort. We review the technique of
      diagnostic Lumbar Puncture including anatomy, needle selection, needle insertion,
      measurement of opening pressure, Cerebrospinal Fluid (CSF) specimen handling and
      after care. We also make some quality improvement suggestions for those designing
      services incorporating diagnostic Lumbar Puncture. 

PMID- 25075139
TI  - Malignant melanoma: a pictorial review.

PMID- 25075140
TI  - Robert Alexander McCance, and his forays into Experimental Medicine with Elsie
      Widdowson.

PMID- 25075141
TI  - Cholecystostomy for acalculous cholecystitis with haemobilia in a lung transplant
      patient; a case report.

PMID- 25075143
TI  - "No time for teaching at our teaching hospitals.".

PMID- 25075142
TI  - Dialysis related amyloid arthropathy on 18FDG PET-CT.

PMID- 25075144
TI  - Acute fulminant necrotising lymphocytic myocarditis in a patient with mixed
      connective tissue disease: a rapid clinical response to immunosuppression.

PMID- 25075145
TI  - Molecular profiling of gliomas--time for a regional service.

PMID- 25075146
TI  - A shotgun injury to the buttocks; getting to the heart of the matter.

PMID- 25075149
TI  - So you want to be a medical student in the UK (and you come from mainland
      Europe)?

PMID- 25075148
TI  - More sugar to the top of the table.

PMID- 25075150
TI  - Retinal hemorrhage in abusive head trauma: finding a common language.
AB  - PURPOSE: To assess the performance of a refined Web-based tool for documenting
      retinal hemorrhage characteristics in suspected abusive head trauma. METHODS:
      Using a comprehensive tabular secure platform, with access to digital images in
      color, black and white, and 4-zone system schematic overlay, four pediatric
      ophthalmologists performed pilot testing with 80 images for tool refinement. In a
      second phase, retinal hemorrhages were documented by number, zone, and type.
      Interobserver agreement was calculated using the Fleiss kappa coefficient.
      Intraobserver agreement was calculated using Cohen's kappa statistic. We used
      surface area mapping software for further analysis. RESULTS: Interobserver
      agreement was good (kappa 0.4-0.6) and very good (kappa 0.6-0.8) for all
      questions in Zone A (peripapillary). For zones C (midperiphery) and D (peripheral
      retina), agreement was very good for all questions except number of hemorrhages,
      for which agreement was good. Zone B (macula) showed good and fair agreement
      except for superficial hemorrhage, for which agreement was poor. There was very
      good intraobserver agreement for number (kappa 0.68, 0.65, 0.67) and type of
      hemorrhages in zones A, B, and C. Surface area mapping results revealed no
      significant differences between zones A and B. Zones C and D had significantly
      less hemorrhage than A and B. CONCLUSIONS: Our tool performed with good or very
      good interobserver and intraobserver agreement in almost all domains. We
      attribute zone B underperformance to the significant increased area covered by
      hemorrhages compared to zones C and D and the lack of contrast with normal
      anatomical structures in zone A.

PMID- 25075151
TI  - Increasing Migration, Diverging Communities: Changing Character of Migrant
      Streams in Rural Thailand.
AB  - This paper studies how increasing migration changes the character of migrant
      streams in sending communities. Cumulative causation theory posits that past
      migration patterns determine future flows, as prior migrants provide resources,
      influence, or normative pressures that make individuals more likely to migrate.
      The theory implies exponentially increasing migration flows that are decreasingly
      selective. Recent research identifies heterogeneity in the cumulative patterns
      and selectivity of migration in communities. We propose that this heterogeneity
      may be explained by individuals' differential access to previously accumulated
      migration experience. Multi-level, longitudinal data from 22 rural Thai
      communities allow us to measure the distribution of past experience as a proxy
      for its accessibility to community members. We find that migration becomes a less
      selective process as migration experience accumulates, and migrants become
      increasingly diverse in socio-demographic characteristics. Yet, selectivity
      within migrant streams persists if migration experience is not uniformly
      distributed among, and hence not equally accessible to, all community members.
      The results confirm that the accumulation and distribution of prior migrants'
      experiences distinctly shape future migration flows, and may lead to diverging
      cumulative patterns in communities over time.

PMID- 25075152
TI  - HEALTHIER, WEALTHIER, AND WISER: A DEMONSTRATION OF COMPOSITIONAL CHANGES IN
      AGING COHORTS DUE TO SELECTIVE MORTALITY.
AB  - The gradual changes in cohort composition that occur as a result of selective
      mortality processes are of interest to all aging research. We present the first
      illustration of changes in the distribution of specific cohort characteristics
      that arise purely as a result of selective mortality. We use data on health,
      wealth, education, and other covariates from two cohorts (the AHEAD cohort, born
      1900-23 and the HRS cohort, born 1931-41) included in the Health and Retirement
      Survey, a nationally representative panel study of older Americans spanning
      nearly two decades (N=14,466). We calculate sample statistics for the surviving
      cohort at each wave. Repeatedly using only baseline information for these
      calculations so that there are no changes at the individual level (what changes
      is the set of surviving respondents at each specific wave), we obtain a
      demonstration of the impact of mortality selection on the cohort characteristics.
      We find substantial changes in the distribution of all examined characteristics
      across the nine survey waves. For instance, the median wealth increases from
      about $90,000 to $130,000 and the number of chronic conditions declines from 1.5
      to 1 in the AHEAD cohort. We discuss factors that influence the rate of change in
      various characteristics. The mortality selection process changes the composition
      of older cohorts considerably, such that researchers focusing on the oldest old
      need to be aware of the highly select groups they are observing, and interpret
      their conclusions accordingly.

PMID- 25075153
TI  - Who supports delayed retirement? A study of older workers in Israel.
AB  - Delayed retirement is a policy measure aimed at ensuring financial stability in
      many countries, but this particular pension reform mechanism still lacks public
      support. Using data from the Israeli sample of the Survey of Health, Ageing and
      Retirement (SHARE) in Europe, this article examines factors which predict support
      for delayed retirement among older Israeli workers (n=556). Hierarchical
      regression analysis of agreement with recently instituted delayed retirement
      measures showed that the perceived societal consequences of the reform were the
      strongest predictors. Older and more educated respondents and those more
      confident in their present workplace were also more likely to support delayed
      retirement. Those who favour state responsibility for care of older people tended
      to support delayed retirement less. The findings suggest that information
      campaigns on the contribution of continued employment to health and family
      solidarity might diminish current fears regarding the delayed retirement-based
      pension reforms. They also imply that non-partisan leadership is needed in order
      to recruit broader public support for such reform.

PMID- 25075154
TI  - Stemness & Niche sans Frontiers - The Cancer Stem Cell myth.

PMID- 25075155
TI  - Cancer stem cells converted from pluripotent stem cells and the cancerous niche.
AB  - Nowadays, the cancer stem cells are considered to be significantly responsible
      for growth, metastasis, invasion and recurrence of all cancer. Cancer stem cells
      are typically characterized by continuous proliferation and self-renewal as well
      as by differentiation potential, while stem cells are considered to differentiate
      into tissue- specific phenotype of mature cells under the influence of micro
      environment. Cancer stem cells should be traced to the stem cells under the
      influence of a micro-environment, which induces malignant tumors. In this review,
      we propose this micro-environment as a 'cancerous niche' and discuss its
      importance on the formation and maintenance of cancer stem cells with the recent
      experimental results to establish cancer stem cell models from induced
      pluripotent stem cells. These models of cancer stem cell will provide the great
      advantages in cancer research and its therapeutic applications in the future. 

PMID- 25075156
TI  - Current status of cancer immunotherapy.
AB  - To prove clinical benefits of cancer vaccine is currently difficult, except for
      one phase III trial has documented improved overall survival with the vaccine,
      Sipuleucel-T, although induction of anti-tumor immune responses through cancer
      vaccine is theoretically promising and would be straightforward. In contrast,
      immune checkpoint blockade with anti-CTLA4 mAb and anti-PD-1 mAb has demonstrated
      clear evidence of objective responses including improved overall survival and
      tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple
      cancer types. In addition, there is a promising novel cancer immunotherapy, CAR
      therapy-a personalized treatment that involves genetically modifying a patient's
      T-cells to make them target tumor cells. We are now facing new era of cancer
      immunotherapy. 

PMID- 25075157
TI  - Effects of umbilical cord tissue mesenchymal stem cells (UCX(r)) on rat sciatic
      nerve regeneration after neurotmesis injuries.
AB  - Peripheral nerves have the intrinsic capacity of self-regeneration after
      traumatic injury but the extent of the regeneration is often very poor.
      Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may
      play an important role in tissue regeneration through the secretion of soluble
      trophic factors that enhance and assist in repair by paracrine activation of
      surrounding cells. In the present study, the therapeutic value of a population of
      umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX((r))),
      was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to
      promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as
      well as reduce the flush away effect of the cells after administration, a
      commercially available haemostatic sealant, Floseal((r)), was used as vehicle.
      Both, functional and morphologic recoveries were evaluated along the healing
      period using extensor postural thrust (EPT), withdrawal reflex latency (WRL),
      ankle kinematics analysis, and either histological analysis or stereology, in the
      hyper-acute, acute and chronic phases of healing. The histological analysis of
      the hyper-acute and acute phase studies revealed that in the group treated with
      UCX((r)) alone the Wallerian degeneration was improved for the subsequent process
      of regeneration, the fiber organization was higher, and the extent of fibrosis
      was lower. The chronic phase experimental groups revealed that treatment with
      UCX((r)) induced an increased number of regenerated fibers and thickening of the
      myelin sheet. Kinematics analysis showed that the ankle joint angle determined
      for untreated animals was significantly different from any of the treated groups
      at the instant of initial contact (IC). At opposite toe off (OT) and heel rise
      (HR), differences were found between untreated animals and the groups treated
      with either uCx((r)) alone or UCX((r)) administered with Floseal((r)). Overall,
      the UCX((r)) application presented positive effects in functional and morphologic
      recovery, in both the acute and chronic phases of the regeneration process.
      Kinematics analysis has revealed positive synergistic effects brought by
      Floseal((r)) as vehicle for MSCs. 

PMID- 25075158
TI  - Multi-atlas segmentation with particle-based group-wise image registration.
AB  - We propose a novel multi-atlas segmentation method that employs a group-wise
      image registration method for the brain segmentation on rodent magnetic resonance
      (MR) images. The core element of the proposed segmentation is the use of a
      particle-guided image registration method that extends the concept of particle
      correspondence into the volumetric image domain. The registration method performs
      a group-wise image registration that simultaneously registers a set of images
      toward the space defined by the average of particles. The particle-guided image
      registration method is robust with low signal-to-noise ratio images as well as
      differing sizes and shapes observed in the developing rodent brain. Also, the use
      of an implicit common reference frame can prevent potential bias induced by the
      use of a single template in the segmentation process. We show that the use of a
      particle guided-image registration method can be naturally extended to a novel
      multi-atlas segmentation method and improves the registration method to
      explicitly use the provided template labels as an additional constraint. In the
      experiment, we show that our segmentation algorithm provides more accuracy with
      multi-atlas label fusion and stability against pair-wise image registration. The
      comparison with previous group-wise registration method is provided as well.

PMID- 25075159
TI  - Transradial approach to cardiovascular interventions: an update.
AB  - Background Since the first cardiac catheterization in 1929, the procedure has
      continually evolved with advances in understanding, capabilities, and ease of
      operation. Though historically performed by cut down of the brachial artery,
      cardiologists soon learned that transfemoral access was both easier to perform
      and more efficacious with regard to patient outcome. In the last 20 years, the
      transradial approach has been adopted, and is being utilized with increasing
      frequency. Methods We conducted a survey of literature published concerning
      safety, efficacy, cost-effectiveness, and global uptake of transradial
      catheterization with specific attention to how transradial interventions compare
      with transfemoral interventions. Results This review of literature indicates that
      when performed by an experienced interventionalist, radial catheterization is as
      effective as femoral catheterization and has additional benefits of shorter
      length of hospital stay and reduced patient costs. Transradial access is superior
      to transfemoral access in some, but not all, clinical scenarios; in addition, it
      is an effective alternative for catheterization in patients contraindicated for
      transfemoral procedures. Adoption of radial access in the United States is at a
      faster rate than previously expected, though rate of use varies drastically
      worldwide. Conclusion The transradial approach is an excellent option for
      carrying out cardiovascular interventions, and will be adopted by more
      cardiologists in the upcoming years. 

PMID- 25075160
TI  - The role of imaging in hypertensive heart disease.
AB  - Hypertensive heart disease (HHD) describes a spectrum of target organ response
      that includes left ventricular hypertrophy, systolic, and diastolic dysfunction.
      A variety of imaging techniques can be used to assess the various aspects of HHD.
      Echocardiography has for many years been the main imaging technique in the
      evaluation of HHD, but there is an increasing role for cardiovascular magnetic
      resonance (CMR) imaging due to its ability to provide an unrestricted field of
      view and noninvasive tissue characterization. This article reviews the current
      role of imaging for HHD with particular focus on echocardiography and CMR
      applications. 

PMID- 25075162
TI  - Aiming at one-stage corrective surgery for extended thoracic aortic dilatation.
AB  - Definitive treatment of extended thoracic aortic dilatation is a major surgical
      challenge. Histopathology of resected thoracic aortic wall may reveal undiagnosed
      aortitis affecting outcome. We sought to investigate the benefit of thorough
      histopathology after one-stage corrective surgery for the treatment of extended
      thoracic aortic dilatation. Five patients underwent one-stage corrective surgery
      using the hybrid open arch repair by the frozen elephant trunk together with
      endovascular aortic grafting. A representative sample of the resected aortic arch
      was procured for histology. T- and B-lymphocytes, plasma cells, macrophages, and
      immunoglobulin G4 (IgG4) positivity were evaluated by immunohistochemistry. The
      mean preoperative maximum aortic diameter was 54 mm (range, 41-79 mm). The mean
      follow-up was 18 months (range, 1-24 months). As confirmed by computed tomography
      (CT) upon follow-up, complete thrombosis of the false lumen at the level of the
      frozen elephant trunk was achieved in all patients with dissection. One patient
      was operated due to atherosclerotic dilatation of the thoracic aorta, and
      postoperative CT showed successful exclusion of the atherosclerotic dilatation;
      this 75-year-old man was diagnosed with IgG4-positive aortitis and experienced
      unexpected blindness after surgery without evidence of emboli or long-term
      neurological impairment upon repeated brain CT. The hybrid open arch repair by
      the frozen elephant trunk and simultaneous endovascular repair is a feasible
      choice for one-stage surgery through sternotomy aiming at definitive treatment of
      extended thoracic aortic pathology. However, systematic evaluation of
      inflammation may reveal concealed aortitis affecting postoperative outcome and
      need for long-term surveillance. 

PMID- 25075161
TI  - A Randomized Comparison between Everolimus-Eluting Stent and Cobalt Chromium
      Stent in Patients with Acute ST-Elevation Myocardial Infarction Undergoing
      Primary Percutaneous Coronary Intervention Using Routine Intravenous
      Eptifibatide: The X-MAN (Xience vs. Multi-Link Stent in Acute Myocardial
      Infarction) Trial, A Pilot Study.
AB  - The objective of this study is to determine the efficacy and safety of an
      everolimus-eluting stent (EES/Xience; Abbott Vascular, Santa Clara, CA) compared
      with a cobalt chromium stent (CoCr/Multi-Link Vision; Abbott Vascular) in
      patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary
      percutaneous coronary intervention (PCI) with routine administration of
      eptifibatide infusion. This is a prospective, single center, randomized trial
      comparing EES (n = 75) and CoCr stent (n = 75) implantation in patients with
      acute STEMI undergoing primary PCI. Intravenous eptifibatide administration was
      mandatory by protocol in this pilot study. The primary efficacy endpoint was
      major adverse cardiac events (MACE) at 30 days, defined as the composite of
      death, reinfarction, and target vessel revascularization. Secondary safety
      endpoints were stent thrombosis at 30 days and in-hospital bleeding event. Acute
      reperfusion parameters were also assessed. One-month MACE rate did not differ
      between EES and CoCr group (1.3 vs. 1.3%, p = 1.0). No stent thrombosis cases
      were observed in the EES group. The groups did not differ with respect to in
      hospital bleeding events (5 vs. 9%, p = 0.37), achievement of final thrombolysis
      in myocardial infarction flow 2 or 3 (p = 0.21), achievement of myocardial blush
      grade 2 or 3 (p = 0.45), creatine kinase-MB level at 8 to 12 hours after stenting
      (p = 0.29), and left ventricular ejection fraction (p = 0.21). This pilot study
      demonstrates that after one-month follow-up, the use of EES is as safe and
      effective as the use of CoCr stents in patients with acute STEMI undergoing
      primary PCI with routine administration of intravenous eptifibatide. 

PMID- 25075163
TI  - Impact of renal artery stent implantation on hypertension in patients with
      hemodialysis.
AB  - The benefit from renal artery stent implantation to treat atherosclerotic renal
      artery stenosis (ARAS) is not well understood in hemodialysis patients. We sought
      to evaluate the effects of renal artery stenting on hypertension of hemodialysis
      patients. Renal artery stent implantation was successfully performed on eight
      hypertensive hemodialysis patients with ARAS (mean +/- SD, 66 +/- 10 years; men
      6, women 2). Blood pressure was measured by automated oscillometric recordings
      just before hemodialysis. Mean values of the blood pressure, measured 12 times a
      month, were used for blood pressure analysis. Values of systolic blood pressure
      decreased at 6 months after renal artery stent implantation (162.6 +/- 29.7 to
      121.1 +/- 23.3 mm Hg, p = 0.0015). Values of diastolic blood pressure also
      decreased from 77.6 +/- 13.6 to 65.6 +/- 7.2 mm Hg (p = 0.02). Renal artery stent
      implantation for ARAS had a beneficial effect on hypertension in hemodialysis
      patients. 

PMID- 25075164
TI  - Rapamune does not attenuate high cholesterol-induced atherosclerosis in rabbits.
AB  - Solid-organ transplant recipients are prone to develop atherosclerosis. The
      objectives of this study were to investigate the effects of Rapamune (Wyeth
      Canada, Saint-Larent, QC, Canada) on the rabbit model of atherosclerosis. The
      rabbits were assigned to four groups: group I, regular diet (control); group II,
      1% cholesterol diet; group III, control with Rapamune (1 mg/kg/d orally); and
      group IV, high cholesterol diet with Rapamune. Blood samples for serum lipids
      (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol
      [LDL-C], high-density lipoprotein cholesterol [HDL-C]), as well as
      malondialdehyde, and protein carbonyls, the indices of oxidative stress were
      collected at the end of 2 months on the respective diet regimen. Aortic tissue
      for atherosclerotic changes were also collected for oxidative stress indices were
      also collected. Rapamune reduced serum levels of TG, TC, LDL-C, and HDL-C.
      Rapamune elevated the oxidative stress in rabbits on high cholesterol diet.
      Rapamune did not attenuate extent of atherosclerosis (group II vs. group IV,
      45.00 +/- 12.00 vs. 57.28 +/- 2.99%); intimal thickness (group II vs. group IV,
      32.38 +/- 7.14 * 10(3) vs. 21.90 +/- 11.98 * 10(3) MUm(2)); intimal/medial ratio
      (group II vs. group IV, 0.50 +/- 0.06 vs. 0.35 +/- 0.06); and macrophage
      accumulation (group II vs. group IV, 69.72 +/- 5.02 vs. 61.52 +/- 8.94%) in the
      intima of rabbits on high cholesterol diet. The data suggest that (1) Rapamune
      increased the oxidative stress in rabbits on high cholesterol diet and (2)
      Rapamune did not attenuate the hypercholesterolemic atherosclerosis in the rabbit
      model. 

PMID- 25075165
TI  - Endovascular repair of a large ruptured abdominal aortic aneurysm using monitored
      anesthesia care and local anesthesia.
AB  - Over the last decade, there has been a paradigm shift in the treatment of
      ruptured abdominal aortic aneurysm (AAA) from open repair to endovascular
      aneurysm repair (EVAR). Regardless of the method used during emergent rupture,
      open verses endovascular repair, the overall mortality remains high. Recent
      studies have compared patient outcomes using different types of anesthesia during
      elective EVAR procedures. The data show that during an elective EVAR, monitored
      anesthesia care (MAC) with local anesthesia is not only just as safe as general
      anesthesia, but it offers other potential benefits as well. There is limited data
      in regards to patient outcomes using MAC and local anesthesia during cases of
      large ruptured aneurysms that are treated with EVAR. This case report discusses
      the treatment of a patient who presented with a large 13 cm ruptured AAA which
      was successfully repaired using EVAR with MAC and local anesthesia. 

PMID- 25075166
TI  - Predictors and prognostic implications of major adverse cardiovascular events
      after renal transplant: 10 years outcomes in 321 patients.
AB  - Renal transplantation is the treatment of choice in patients with end-stage renal
      disease. Major adverse cardiac events (MACE) are common after renal transplant,
      especially in the perioperative period, leading to excess morbidity and
      mortality. The predictors and long-term prognostic implications of MACE are
      poorly understood. We analyzed predictors and implications of MACE in a cohort of
      321 consecutive adult patients, who received renal allograft transplantation
      between 1995 and 2003 at our institution. The characteristics of 321 patients
      were: age at transplant 44 +/- 13 years, 60% male, 36% diabetes mellitus (DM),
      left ventricular ejection fraction (LVEF) 60 +/- 16%. MACE occurred in 21
      patients with cumulative rate of 6.5% over 3 years after renal transplant, 57%
      occurring within 30 days, 67% within 90 days, and 86% within 180 days. MACE was
      not predicted by any clinical or pharmacological variables including age, gender,
      hypertension, DM, prior myocardial infarction, smoking, duration of dialysis,
      LVEF, or therapy with beta-blockers (BB), angiotensin converting enzyme
      inhibitors, or calcium channel blockers. However, a clinical decision to perform
      a stress test or a coronary angiogram was predictive of higher MACE rate. MACE,
      irrespective of type, was independently associated with higher mortality over a
      period up to 15 years and this seemed to be blunted by BB therapy. MACE rate
      after renal transplantation decreases over time, most occurring in the first 90
      days and is not predicted by any of the traditional risk factors or drug
      therapies. It is associated with higher long-term mortality. 

PMID- 25075167
TI  - Aneurysmal Coronary Artery Fistulae: How Big is Big Enough?
AB  - Coronary artery fistula (CAF) is the most common congenital anomaly of coronary
      arteries. Management strategies for CAF causing symptoms and large shunting are
      well described. With growing use of noninvasive imaging modalities, the diagnosis
      of asymptomatic CAF has increased. This poses challenge on the management of CAF
      with high-risk features as therapeutic strategy of incidentally found CAF remains
      open to debate. The actual risk of complications in such cases is mere
      speculations based on small studies and need to be revisited. We describe the
      case of an asymptomatic 78-year-old woman with a large saccular coronary aneurysm
      associated with coronary artery to pulmonary artery fistula that was treated
      successfully using coils. We discuss the updated literature on the management of
      CAF as well. 

PMID- 25075168
TI  - Isolated single coronary artery presenting as acute coronary syndrome: case
      report and review.
AB  - Congenital single coronary artery is commonly associated with complex congenital
      heart diseases and manifests in infancy or childhood. But isolated single
      coronary artery is a rare congenital anomaly which can present as acute coronary
      syndrome in adults. The aim of the work is to discuss on isolated single coronary
      artery in two adults presenting as acute coronary syndrome. The first case
      underwent coronary angiography (CAG) through right radial route, but switched
      over to femoral for confirmation of diagnosis and due to radial spasm. An aortic
      root angiogram was done to rule out presence of any other coronary ostia. It
      revealed a single coronary artery originating from right sinus of valsalva. After
      giving rise to posterior descending artery branch at crux, it continued in the
      atrioventricular groove to the anterior basal surface of the heart and traversed
      as anterior descending artery. There was no atheromatous occlusive stenosis. This
      is R-I type single coronary artery as per Lipton classification. In the second
      case, angiography was completed through right radial route. It revealed a single
      coronary artery arising from right aortic sinus. Anterior descending and
      circumflex branch were originating from proximal common trunk of the single
      coronary artery and supplying the left side of the heart. The right coronary
      artery has diffuse atheromatous disease without significant stenosis in any major
      branch. This is R-III C type as per Lipton classification. A coronary anomaly of
      both origin and course is very rare. It may be encountered in adults evaluated
      for atherosclerotic coronary heart disease. Knowledge and understanding of
      anatomical types of this congenital anomaly will reduce time, anxiety,
      complications during CAG and cardiac surgery. 

PMID- 25075169
TI  - Case Report and Review of Literature: Late Retrograde Type A Aortic Dissection
      With Rupture after Repair of Type B Aortic Dissection with a GORE TAG
      Endovascular Prosthesis.
AB  - Acute aortic dissection is the most common catastrophic condition of the aorta.
      Treatment options include open surgery and thoracic endovascular aortic
      reconstruction (TEVAR). We present a late Type A dissection as a complication of
      the management of descending aortic dissections with TEVAR and a review of the
      literature. TEVAR of the thoracic aorta is a viable treatment option for the
      management of complicated descending thoracic aortic dissections. Careful patient
      selection is necessary as medical therapy successfully treats the majority of
      uncomplicated Type B dissections. TEVAR should be reserved for patients with
      complicated Type B dissections or those who fail nonoperative management. Close
      postoperative monitoring is necessary when TEVAR is performed and should be
      accompanied by lifelong surveillance. A high level of suspicion is important to
      identify retrograde Type A dissections in these patients given its rarity and the
      ambiguity of its clinical presentation. 

PMID- 25075170
TI  - An Examination of Exposure to Traumatic Events and Symptoms and Strengths for
      Children Served in a Behavioral Health System of Care.
AB  - The present study examined how exposure to traumatic events impacts children with
      severe emotional disturbance who are being served in a school-based system of
      care. Multilevel growth curve models were used to examine the relationships
      between a child's history of traumatic events (physical abuse, sexual abuse, or
      domestic violence) and behavioral and emotional strengths, internalizing problem
      behaviors, or externalizing problem behaviors over 18 months. Results indicate
      that children receiving services (N = 134) exhibited increased emotional and
      behavioral strengths and decreased internalizing and externalizing problem
      behaviors from enrollment to 18 months follow-up. Children with a history of
      traumatic events improved more slowly than children without such a history on
      both strengths and internalizing problem behaviors, even after controlling for
      dosage of services received and other characteristics previously found to predict
      outcomes. Gender was also related to improvement in internalizing symptoms.
      Results highlight the continued need to assess the impact of exposure to
      traumatic events for children served in a system of care.

PMID- 25075171
TI  - Assessing Client Progress Session by Session in the Treatment of Social Anxiety
      Disorder: The Social Anxiety Session Change Index.
AB  - Frequent assessment during therapy can improve treatments and provide
      accountability. However, clinicians often do not monitor progress because of the
      time it takes to administer and score assessments. In response, the Social
      Anxiety Session Change Index (SASCI) was developed. The SASCI is a short, easily
      administered rating of subjective improvement that asks clients with social
      anxiety disorder how much they have changed since the beginning of therapy.
      Change on the SASCI was related to change in fear of negative evaluation, a core
      aspect of social anxiety, and to clinician-rated improvement, but not to ratings
      of anxiety sensitivity or depression. Because it is brief and easily
      interpretable, the SASCI can be used in a variety of clinical settings to monitor
      change across therapy. The SASCI is presented along with examples of how the
      information gathered from frequent administration can inform clinical practice.

PMID- 25075172
TI  - Can dynamic contour tonometry and ocular pulse amplitude help to detect severe
      cardiovascular pathologies?
AB  - We demonstrate the close relationship between a conspicuous ocular pulse
      amplitude and severe underlying cardiovascular disease. Two otherwise symptom
      free glaucoma patients without any previously diagnosed underlying cardiovascular
      pathology but with a conspicuous ocular pulse amplitude and who underwent routine
      examinations in our glaucoma department were referred to the appropriate
      specialty for further diagnostic procedures. In both patients, the diagnosis of a
      tachyarrhythmia was made as suspected on dynamic contour tonometry measurements.
      In addition to medical treatment, one patient underwent electric cardioversion
      and the second patient was scheduled for pacemaker implantation. A third patient
      with an unexpected high ocular pulse amplitude despite severe cardiovascular
      pathology underwent major surgery due to an aortic aneurysm. Carotid stenosis was
      diagnosed due to side differences in ocular pulse amplitude as well. Ocular pulse
      amplitude might be a noninvasive and affordable screening tool and could be used
      to detect severe cardiovascular disease. A prospective study including a larger
      number of patients is needed to prove this hypothesis. 

PMID- 25075173
TI  - Frequency-doubling technology perimetry and multifocal visual evoked potential in
      glaucoma, suspected glaucoma, and control patients.
AB  - INTRODUCTION: The gold standard in functional glaucoma evaluation is standard
      automated perimetry (SAP). However, SAP depends on the reliability of the
      patients' responses and other external factors; therefore, other technologies
      have been developed for earlier detection of visual field changes in glaucoma
      patients. The frequency-doubling perimetry (FDT) is believed to detect glaucoma
      earlier than SAP. The multifocal visual evoked potential (mfVEP) is an objective
      test for functional evaluation. OBJECTIVE: To evaluate the sensitivity and
      specificity of FDT and mfVEP tests in normal, suspect, and glaucomatous eyes and
      compare the monocular and interocular mfVEP. METHODS: Ninety-five eyes from 95
      individuals (23 controls, 33 glaucoma suspects, 39 glaucomatous) were enrolled.
      All participants underwent a full ophthalmic examination, followed by SAP, FDT,
      and mfVEP tests. RESULTS: The area under the curve for mean deviation and pattern
      standard deviation were 0.756 and 0.761, respectively, for FDT, 0.564 and 0.512
      for signal and alpha for interocular mfVEP, and 0.568 and 0.538 for signal and
      alpha for monocular mfVEP. This difference between monocular and interocular
      mfVEP was not significant. CONCLUSION: The FDT Matrix was superior to mfVEP in
      glaucoma detection. The difference between monocular and interocular mfVEP in the
      diagnosis of glaucoma was not significant.

PMID- 25075174
TI  - Clinical features of diabetic patients referred by general physicians due to less
      ophthalmic examinations.
AB  - BACKGROUND: The purpose of this study was to determine the clinical features of
      patients with type 2 diabetes, and less ophthalmic examinations, referred by
      general physicians to ophthalmologists. METHODS: The medical charts of 327
      patients with type 2 diabetes referred to our department from general physicians
      were reviewed. A detailed medical history was taken and a complete ophthalmic
      examination was performed for all patients. The patients were divided into two
      groups, ie, those with a history of missing ophthalmic examinations for more than
      a year (noncompliant group) and those with no previous ophthalmic examinations
      (never-examined group). Serum levels of glycosylated hemoglobin and creatinine,
      estimated glomerular filtration rate, and urine albumin/creatinine ratio were
      obtained from medical records. RESULTS: Of the 327 patients, 102 had diabetic
      retinopathy (31.2%), with a mean best-corrected visual acuity of 0.037+/-0.36
      logMAR (logarithm of the minimum angle of resolution) units. Of the 327 patients,
      203 were in the never-examined group and 124 were in the noncompliant group. The
      incidence of diabetic retinopathy in the noncompliant group was significantly
      higher than that in the never-examined group (P<0.001). Best-corrected visual
      acuity in the noncompliant group was significantly worse than in the never
      examined group (P=0.004). Glycosylated hemoglobin levels and estimated glomerular
      filtration rate in the noncompliant group were significantly lower than in the
      never-examined group (P<0.001 and P<0.003, respectively); serum creatinine levels
      and urine albumin/creatinine ratio were significantly higher (P=0.020 and
      P=0.001, respectively). The severity of the diabetic retinopathy was
      significantly correlated with compliance in terms of ophthalmic examinations and
      with urine albumin/creatinine ratio (multiple regression analysis, P=0.047 and
      P<0.001, respectively). CONCLUSION: Our results show that diabetic patients
      referred from general physicians due to less ophthalmic examinations generally
      have good visual acuity, but one third of them have diabetic retinopathy. A
      history of missing ophthalmic examinations and albuminuria are risk factors for
      diabetic retinopathy.

PMID- 25075175
TI  - Profile and potential of ixabepilone in the treatment of pancreatic cancer.
AB  - The management of metastatic pancreatic adenocarcinoma is a challenge for medical
      oncologists because of both the aggressive nature of the disease and the relative
      paucity of effective systemic treatments with activity against this type of
      tumor. In the effort to discover new agents and combinations that may augment the
      therapeutic arsenal available for the management of this cancer, early phase
      clinical trials have been performed using ixabepilone, an epothilone B analog,
      with promising results. Targeting the microtubule system with certain taxanes in
      the management of pancreatic adenocarcinoma has been validated; ixabepilone also
      targets the microtubule system, interfering with it in an alternate manner from
      the taxane mechanism. Ixabepilone has demonstrated activity in cancers that have
      become taxane-resistant as well as those that never had any demonstrable taxane
      susceptibility. The available data for the use of ixabepilone in the management
      of pancreatic adenocarcinoma are limited but promising. Single-arm studies have
      demonstrated both clinical efficacy and tolerable toxicity for the use of
      ixabepilone as monotherapy. The trial data available for ixabepilone used as a
      part of combination therapy are similar: it has been paired with chemotherapy
      (carboplatin, irinotecan) and biologic therapy (dasatinib, sunitinib) at the
      Phase I level to treat solid tumors in general, again with tolerable side effects
      and a suggestion of benefit. A single Phase II study has evaluated combination
      therapy with ixabepilone in the management of patients with pancreatic cancer,
      pairing it with cetuximab with clinical benefit. Although these trials are
      promising with regard to addition of ixabepilone to the slim armamentarium for
      management of pancreatic cancer, further work is still to be done. Importantly,
      this work bears the burden of not only validating the clinical benefit of
      ixabepilone, but also of determining whether this benefit is enhanced in any way
      by combination therapy, and where ixabepilone fits in the sequence of management
      for patients with metastatic pancreatic cancer. 

PMID- 25075176
TI  - A preliminary study of painless and effective transdermal botulinum toxin A
      delivery by jet nebulization for treatment of primary hyperhidrosis.
AB  - BACKGROUND: Hyperhidrosis is a chronic disease characterized by increased sweat
      production. Local injections of botulinum toxin A (BTX-A) have been extensively
      used for treatment of primary hyperhidrosis (idiopathic). The current treatment
      for this condition involves several intradermal injections, resulting in poor
      patient compliance due to injection-related pain. Therefore, new protocols,
      including an improved anesthetic regimen, are required. AIM: We designed the
      present study to determine whether JetPeelTM-3, a medical device used for
      transdermal delivery of drugs by jet nebulization, could be used to deliver
      lidocaine prior to the standard multiple BTX-A injections or deliver lidocaine
      together with BTX-A in order to determine the protocol giving better results in
      terms of procedure-related pain, sweating, and patient satisfaction in subjects
      affected by primary axillary, palmar or plantar hyperhidrosis. MATERIALS AND
      METHODS: Twenty patients with a visual analog scale (VAS) sweating score >= 8 cm
      were randomized to receive lidocaine 2% (5 mL) delivered by JetPeelTM-3 followed
      by multiple injections of BTX-A (100 units) or lidocaine 2% (5 mL) and BTX-A (50
      units) delivered together by JetPeelTM-3. Effect of treatment on sweating was
      measured by VAS (0= minimum sweating; 10= maximum sweating) at 3-month follow-up.
      Pain induced by the procedure was assessed by VAS (0= minimum pain; 10= maximum
      pain) immediately after the procedure. Patient satisfaction was assessed at 3
      month follow-up using a 5-point scale (1= not at all satisfied; 2= not satisfied;
      3= partially satisfied; 4= satisfied; 5= highly satisfied). RESULTS: Both
      treatment modalities reduced sweating at 3-month follow-up, if compared with
      baseline (all P<0.001). Delivery of lidocaine and BTX-A by JetPeelTM-3 resulted
      in lower procedure-related pain and reduced sweating, if compared with lidocaine
      delivered by JetPeelTM-3 followed by multiple BTX-A injections (all P<0.001).
      Patient satisfaction with the procedure was higher in the group receiving
      lidocaine and BTX-A treatment by JetPeelTM-3, if compared with lidocaine
      delivered by JetPeelTM-3 followed by multiple BTX-A injections (P<0.001). No side
      effects were observed in both groups. CONCLUSION: Lidocaine and BTX-A can be
      safely delivered together by JetPeelTM-3 to treat primary palmar, plantar and
      axillary hyperhidrosis, resulting in lower procedure-related pain, improved
      sweating and higher patient satisfaction, if compared with lidocaine delivered by
      JetPeelTM-3 followed by standard BTX-A injection therapy. Our protocol delivering
      lidocaine and BTX-A together by JetPeelTM-3 requires a reduced quantity of BTX-A,
      further supporting the use of the transdermal drug delivery by jet nebulization
      over standard injection therapy for treatment of primary hyperhidrosis.

PMID- 25075177
TI  - Prostatic urethral angle might be a predictor of treatment efficacy of alpha
      blockers in men with lower urinary tract symptoms.
AB  - PURPOSE: We investigated the association of the prostatic urethral angle (PUA)
      with peak urinary flow rate (Qmax) and the severity of lower urinary tract
      symptoms (LUTS) on the aging male. We also evaluated the effect of the PUA on the
      treatment efficacy of tamsulosin on men with LUTS. MATERIALS AND METHODS: The
      records were obtained from a prospective database for first-visit male patients
      with LUTS in the outpatient department of our institution. These patients
      underwent a detailed physical examination and taking of medical history. A
      transrectal ultrasound was performed on these patients. The prostate size, length
      of intravesical prostatic protrusion (IPP), PUA, and International Prostate
      Symptom Score (IPSS) of the patients were evaluated. Uroflowmetry and a bladder
      scan for residual urine were also performed on every patient. Tamsulosin 0.2 mg
      per day was prescribed. The IPSS and uroflowmetry were reevaluated after they had
      received treatment for 3 months. RESULTS: A total of 178 patients were included,
      and 149 of them completed this cohort study. The mean PUA was 48.32 degrees +/
      13.74 degrees . The mean prostate volume was 39.19+/-20.87 mL, and the mean IPP
      was 5.67+/-7.85 mm. On multivariate linear regression analysis, the PUA was
      independently associated with the IPSS (P<0.001), Qmax (P=0.004), post-treatment
      IPSS change (P=0.032), and post-treatment Qmax change (P<0.001). However, the
      prostate volume and IPP were not associated with these clinical items.
      CONCLUSION: The PUA is significantly associated with Qmax and IPSS in men with
      LUTS. The PUA is also inversely correlated with changes in Qmax and IPSS after
      tamsulosin treatment. Namely, the PUA might be a predictor for the treatment
      efficacy of alpha-blockers in aging men with LUTS.

PMID- 25075178
TI  - Locus of pain control associated with medication adherence behaviors among
      patients after an orthopedic procedure.
AB  - BACKGROUND: Locus of pain control (LPC) is characterized by the behavior of
      people coping with their health problems, as a result of their own actions
      (internal control) or external factors or other people (external control). This
      parameter can be associated with medication adherence, in addition to other
      psychosocial factors that may also influence this behavior. This study was
      performed to investigate the influence of the LPC on medication adherence in
      patients undergoing an orthopedic procedure. SUBJECTS AND METHODS: We conducted a
      prospective cohort study on patients who attended an orthopedic clinic for
      arthroscopy treatment. The patients' LPC and pain intensity data were obtained on
      the day of admission through the use of the LPC scale and the visual analog scale
      (VAS), respectively, both being validated tools. After arthroscopic surgery, the
      patients received drug prescriptions and were reassessed after 15 days regarding
      treatment adherence, using the Morisky test. A P-value <0.05 was considered
      statistically significant. RESULTS: We assessed 79 individuals from both the
      internal LPC group (n=35) and external LPC group (n=44) and found that there were
      no group differences in sex, affected limb, cause of injury, repetitive strain
      injury, duration of pain, or pain intensity. However, there was a higher
      proportion of patients in the external LPC group that adhered to the prescribed
      medication compared with the internal LPC group (P<0.01). CONCLUSION: The results
      showed that among patients who underwent an orthopedic procedure, there was a
      higher adherence rate to prescribed medication in the external LPC group compared
      with the internal LPC group.

PMID- 25075179
TI  - The benefit of atrial septal defect closure in elderly patients.
AB  - OBJECTIVE: Closure of an atrial septal defect in elderly patients is
      controversial. The aim of the study was to evaluate the outcomes of transcatheter
      closure of secundum atrial septal defects (ASDs) in elderly patients. PATIENTS
      AND METHODS: From a total of 488 patients with ASDs who underwent transcatheter
      closure, 75 patients aged over 60 years (45 female, 30 male) with a mean age of
      65.3+/-15.7 (60-75) years were analyzed. All patients had an isolated secundum
      ASD with a mean pulmonary blood flow:systemic blood flow of 2.84+/-1.9 (1.5-3.9).
      Symptom-limited treadmill exercise tests with respiratory gas-exchange analysis
      and transthoracic color Doppler echocardiographic study, as well as quality of
      life measured using the Short Form (36) Health Survey (SF-36) were repeated in
      all patients before the procedure and after 12 months of follow-up. RESULTS: The
      atrial septal device was successfully implanted in all patients (procedure time
      37.7+/-4.5 [13-59] minutes, fluoroscopy time 11.2+/-9.9 [6-40] minutes). There
      were no major complications. The defect echo diameter was 17.7+/-15.8 (12-30) mm.
      The mean balloon-stretched diameter of ASDs was 22.4+/-7.9 (14-34) mm. The
      diameter of the implanted devices ranged from 16 to 34 mm. Significant
      improvement of exercise capacity was noted at 6 and 12 months after the
      procedure. Exercise time within 6 months of ASD closure was longer (P<0.001)
      compared to baseline values, and also oxygen consumption increased (P<0.001).
      Seven quality-of-life parameters (except mental health) improved at 12-month
      follow-up compared to baseline data. The mean SF-36 scale increased significantly
      in 66 (88%) patients, with a mean of 46.2+/-19.1 (5-69). As early as 1 month
      after the procedure, a significant decrease of the right ventricular dimension
      and the right atrium dimension was observed (P<0.001). The right ventricular
      dimension decreased in 67 patients (89.3%). CONCLUSION: Closure of ASDs in
      elderly patients caused significant clinical and hemodynamic improvement after
      percutaneous treatment, which was maintained during long-term follow-up,
      justifying this procedure in old age.

PMID- 25075180
TI  - Altered diastolic function and aortic stiffness in Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is closely linked to cardiovascular risk
      factors. METHODS: Echocardiographic studies were performed, including left
      ventricular diastolic functions, left and right atrial conduction times, and
      arterial stiffness parameters, namely stiffness index, pressure-strain elastic
      modulus, and distensibility, on 29 patients with AD and 24 age-matched
      individuals with normal cognitive function. RESULTS: The peak mitral flow
      velocity of the early rapid filling wave (E) was lower, and the peak velocity of
      the late filling wave caused by atrial contraction (A), deceleration time of peak
      E velocity, and isovolumetric relaxation time were higher in the AD group. The
      early myocardial peak (Ea) velocity was significantly lower in AD patients,
      whereas the late diastolic (Aa) velocity and E/Ea ratio were similar between the
      two groups. In Alzheimer patients, stiffness index and pressure-strain elastic
      modulus were higher, and distensibility was significantly lower in the AD group
      compared to the control. Interatrial electromechanical delay was significantly
      longer in the AD group. CONCLUSION: Our findings suggest that patients with AD
      are more likely to have diastolic dysfunction, higher atrial conduction times,
      and increased arterial stiffness compared to the controls of same sex and similar
      age.

PMID- 25075181
TI  - Clinical evaluation of motion and position sense in the upper extremities of the
      elderly using motion analysis system.
AB  - The purpose of this study was to measure kinesthetic accuracy in healthy older
      adults by using arm position and motion matching tests. We investigated the
      effect of task type, joint angle, and matching arm results on kinesthetic
      accuracy in the upper extremities of 17 healthy right-handed older adults.
      Blinded subjects were asked to match positions and motions at four reference
      joint angles: 1) shoulder flexion, 0 degrees -60 degrees ; 2) elbow flexion, 90
      degrees -135 degrees ; 3) wrist extension, 0 degrees -50 degrees  in the sagittal
      plane; and 4) shoulder abduction, 0 degrees -60 degrees  in the frontal plane.
      The absolute difference in angular displacement between the reference and
      matching arms was calculated to determine kinesthetic accuracy. Results showed
      that subjects were more accurate at matching motion than position tasks (P=0.03).
      Shoulder and elbow joints were more sensitive than wrist joints in perceiving
      passive positions and motions (P<0.05). The effect of the matching arm was found
      only when matching the joint angles of shoulder abduction and wrist extension
      (P<0.01). These results are comparable to findings of other studies that used
      machine-generated kinesthetic stimuli. The manual measurement of kinesthetic
      accuracy could be effective as a preliminary screening tool for therapists in
      clinical settings. 

PMID- 25075182
TI  - Quantitative evaluation in combination with nonquantitative evaluation in early
      patellar cartilage osteoarthritis at 3.0 T.
AB  - PURPOSE: To evaluate quantitative T1 and T2 relaxation times and magnetization
      transfer ratios (MTRs) in the early diagnosis of patellar cartilage
      osteoarthritis (OA) and to quantify and possibly refine the current Kellgren
      Lawrence score criteria. MATERIALS AND METHODS: A total of 92 cases of knee
      joints with 40 normal volunteers and 30 patients with OA were prospectively
      evaluated. The knee joints with OA were divided into mild and moderate groups
      according to the Kellgren-Lawrence score criteria. The discriminative analysis
      method was used to analyze the accuracy of the original grouped cases correctly
      classified by age, sex, T1 relaxation times, T2 relaxation times, and MTR values.
      Linear regression analysis was used between T1 relaxation time, T2 relaxation
      time, and MTR values. RESULTS: The mean T1 relaxation times decreased with the
      severity of OA, and a significant difference was only found between the normal
      and moderate OA groups (P<0.05). The mean T2 relaxation times increased, and
      significant differences were found between the normal and mild OA groups and the
      normal and moderate OA groups (P<0.001). The MTR values were 35.8%+/-4.2%,
      36.1%+/-3.2%, and 35.4%+/-3.8%, respectively. There were no significant
      differences between the normal and OA groups. In addition, T1 relaxation times
      were positively correlated with MTR values (P<0.01). A discriminative analysis
      using a synthesis of all the influential factors indicated a high accuracy rate
      (93.9%) for the correct classification of the original grouped cases. CONCLUSION:
      Quantitative T1 and T2 relaxation times were useful in the diagnosis of early OA;
      T2 relaxation times were more relatively sensitive. The functional usefulness of
      MTR values may be limited. T1 relaxation times positively correlated with MTR
      values. Multiple quantitative parameters, combined with some relative
      nonquantitative clinical parameters and Kellgren-Lawrence scores, may be useful
      in the early stage of OA and provide better information for clinical treatment
      and follow-up.

PMID- 25075183
TI  - Age-related changes in central corneal thickness in normal eyes among the adult
      Lithuanian population.
AB  - BACKGROUND: The purpose of this study was to estimate mean central corneal
      thickness (CCT) and determine whether there are any correlations between CCT,
      age, and sex in the adult Lithuanian population. METHODS: A total of 1,650
      Caucasians of Lithuanian origin (aged 18-89 years) comprising 688 (41.7%) men and
      962 (58.3%) women were examined. Subjects were stratified by age into seven
      groups. CCT was measured using ultrasonic pachymetry. Correlations between CCT,
      age, and sex were sought. RESULTS: Mean (+/- standard deviation) CCT for both
      eyes was 544.6+/-30.5 MUm. Mean CCT was 545.2+/-30.5 MUm in the left eye and
      544.6+/-30.5 MUm in the right eye, and was 545.0+/-25.6 MUm in men and 544.4+/
      33.5 MUm in women. Mean CCT was 550.8+/-35.7 MUm in subjects aged 18-29 years,
      557.5+/-27.6 MUm in those aged 30-39 years, 551.3+/-31.4 MUm in those aged 50-59
      years, 544.0+/-31.4 MUm in those aged 50-59 years, 544.2+/-31.6 MUm in those aged
      60-79 years, 535.1+/-27.8 MUm in those aged 70-79 years, and 530.1+/-16.8 MUm in
      those aged 80-89 years. No statistically significant difference in CCT was found
      between the sexes (P>0.05). However, there was a significant difference in
      subjects aged 18-29 years; men had higher CCT than women (P<0.05). A
      statistically significant negative correlation was found between CCT and age (r=
      0.263, P<0.05) that was stronger in men (r=-0.406, P<0.05) than in women (r=
      0.118, P<0.05). CONCLUSION: The mean CCT in adult Lithuanians was 544.6+/-30.5
      MUm, of the left eye 545.2+/-30.5 MUm and of the right - 544.6+/-30.5 MUm. CCT of
      the right eye was equal to the CCT of both eyes. Mean CCT was 545.0+/-25.6 MUm in
      men and 544.4+/-33.5 MUm in women. Young men tended to have higher CCT than
      women. CCT decreases over the lifetime, meaning that older people have thinner
      corneas. CCT's dependence on age is stronger in men.

PMID- 25075184
TI  - Challenging nanoparticles: a target of personalized adhesion prevention strategy.

PMID- 25075185
TI  - Cationic star-shaped polymer as an siRNA carrier for reducing MMP-9 expression in
      skin fibroblast cells and promoting wound healing in diabetic rats.
AB  - BACKGROUND: Excessive expression of matrix metalloproteinase-9 (MMP-9) is
      deleterious to the cutaneous wound-healing process in the context of diabetes.
      The aim of the present study was to explore whether a cationic star-shaped
      polymer consisting of beta-cyclodextrin (beta-CD) core and poly(amidoamine)
      dendron arms (beta-CD-[D3]7) could be used as the gene carrier of small
      interfering RNA (siRNA) to reduce MMP-9 expression for enhanced diabetic wound
      healing. METHODS: The cytotoxicity of beta-CD-(D3)7 was investigated by 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MMT) method in the
      rat CRL1213 skin fibroblast cell line. The transfection efficiency of beta-CD
      (D3)7/MMP-9-small interfering RNA (siRNA) complexes was determined by confocal
      microscopy and flow cytometry. Quantitative real time (RT) polymerase chain
      reaction was performed to measure the gene expression of MMP-9 after the
      transfection by beta-CD-(D3)7/MMP-9-siRNA complexes. The beta-CD-(D3)7/MMP-9
      siRNA complexes were injected on the wounds of streptozocin-induced diabetic
      rats. Wound closure was measured on days 4 and 7 post-wounding. RESULTS: beta-CD
      (D3)7 exhibited low cytotoxicity in fibroblast cells, and easily formed the
      complexes with MMP-9-siRNA. The beta-CD-(D3)7/MMP-9-siRNA complexes were readily
      taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene
      expression (P<0.01). Animal experiments revealed that the treatment by beta-CD
      (D3)7/MMP-9-siRNA complexes enhanced wound closure in diabetic rats on day 7 post
      wounding (P<0.05). CONCLUSION: beta-CD-(D3)7 may be used as an efficient carrier
      for the delivery of MMP-9-siRNA to reduce MMP-9 expression in skin fibroblast
      cells and promote wound healing in diabetic rats.

PMID- 25075186
TI  - Existence, release, and antibacterial actions of silver nanoparticles on Ag-PIII
      TiO2 films with different nanotopographies.
AB  - Nanotopographical TiO2 films (including nanorod, nanotip, and nanowire
      topographies) were successfully fabricated on the metallic Ti surface via
      hydrothermal treatment and then underwent Ag plasma immersion ion implantation to
      incorporate Ag with TiO2. The surface morphology, phase component, and chemical
      composition before and after Ag-PIII were characterized. In view of the potential
      clinical applications, both Gram-negative Escherichia coli and Gram-positive
      Staphylococcus aureus were used to estimate their antimicrobial effect. The
      nanostructured TiO2 films on a Ti surface exhibit a better bacteriostatic effect
      on both microbes compared to the pristine Ti. The nanotopographies of the TiO2
      films affect the nucleation, growth, and distribution of Ag nanoparticles in the
      films during Ag-PIII process. The Ag nanoparticles are completely embedded into
      the nanorod film while partially exposed out of the nanotip and nanowire films,
      which account for the significant differences in the release behaviors of Ag ions
      in vitro. However, no significant difference exists in their antimicrobial
      activity against both microbes. The antimicrobial actions of the Ag@TiO2 system
      described here consist of two methods - the contact-killing action and the
      release-killing action. Nevertheless, based on the observed results, the contact
      killing action should be regarded as the main method to destroy microbes for all
      the Ag plasma-modified TiO2 nanofilms. This study provides insight to optimize
      the surface design of Ti-based implants to acquire more effective antimicrobial
      surfaces to meet clinical applications.

PMID- 25075187
TI  - Effective inhibition of colon cancer cell growth with MgAl-layered double
      hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through
      apoptotic pathways.
AB  - Colon cancer is the third most common cancer and the third largest cause of
      cancer-related death. Fluorouracil (5-FU) is the front-line chemotherapeutic
      agent for colon cancer. However, its response rate is less than 60%, even in
      combination with other chemotherapeutic agents. The side effects of 5-FU also
      limit its application. Nanoparticles have been used to deliver 5-FU, to increase
      its effectiveness and reduce side effects. Another common approach for colon
      cancer treatment is targeted therapy against the phosphoinositide 3-kinase
      (PI3K)/protein kinase B (Akt) pathway. A recently-invented inhibitor of this
      pathway, BEZ-235, has been tested in several clinical trials and has shown
      effectiveness and low side effects. Thus, it is a very promising drug for colon
      cancer treatment. The combination of these two drugs, especially nanoparticle
      packed 5-FU and BEZ-235, has not been studied. In the present study, we
      demonstrated that nanoparticles of layered double hydroxide (LDH) loaded with 5
      FU were more effective than a free drug at inhibiting colon cancer cell growth,
      and that a combination treatment with BEZ-235 further increased the sensitivity
      of colon cancer cells to the treatment of LDH-packed 5-FU (LDH-5-FU). BEZ-235
      alone can decrease colon cancer HCT-116 cell viability to 46% of the control, and
      the addition of LDH-5-FU produced a greater effect, reducing cell survival to 8%
      of the control. Our data indicate that the combination therapy of nanodelivered 5
      FU with a PI3K/Akt inhibitor, BEZ-235, may promise a more effective approach for
      colon cancer treatment. 

PMID- 25075188
TI  - Pharmacology and clinical potential of vortioxetine in the treatment of major
      depressive disorder.
AB  - VORTIOXETINE IS A NEW MULTIMODAL ACTION ANTIDEPRESSANT WITH TWO TYPES OF ACTION:
      serotonin transporter (SERT) blockade and a strong affinity for several
      serotoninergic receptors. It is an antagonist of the 5-HT3 and 5-HT7 receptors, a
      partial agonist of 5-HT1B, and an agonist of 5-HT1A. Its combined action on SERT
      and four subtypes of serotoninergic receptors increases the extracellular
      concentration of serotonin, dopamine, and noradrenaline. Twelve clinical trials
      have been carried out, nine of which had positive results versus placebo. When
      active comparators were included in the study design, no significant differences
      were found except in one study in which the efficacy of vortioxetine was superior
      to the comparator (agomelatine) in depression resistant to selective serotonin
      reuptake inhibitors (SSRI)/serotonin-norepinephrine reuptake inhibitors (SNRI)
      treatment. Tolerability studies indicate that the drug does not cause any
      important problems on blood tests, vital signs, or on electrocardiography. The
      lack of weight gain and induction of metabolic syndrome and the lack of
      significant changes in the QTc are especially important. The incidence rate of
      sexual dysfunction is low and similar to placebo in various trials. Similarly,
      cognitive function remains intact with vortioxetine. 

PMID- 25075190
TI  - Adjunctive treatment for cognitive impairment in patients with chronic
      schizophrenia: a double-blind, placebo-controlled study.
AB  - Cognitive impairment is closely related to real-life functioning in patients with
      schizophrenia. The aim of the present study was to evaluate the effects of
      adjunctive treatment with donepezil on cognition in patients with chronic
      schizophrenia. This was a 12-week, double-blind, randomized, placebo-controlled
      study of donepezil as an adjunct to antipsychotic drug therapy in patients with
      chronic stable schizophrenia. Sixty-one subjects were randomized to receive
      donepezil 5 mg/day (n=31) and/or placebo (n=30). A nine-test neuropsychological
      assessment battery was administered at baseline and at the end of the study. At
      the 12-week end point, the donepezil group showed significant improvements in the
      Wechsler Memory Scale Third Edition Spatial Span, Brief Visuospatial Memory Test
      total recall and delayed recall, Trail-Making Test Part A, and Category Fluency
      Test-animal naming (all P<=0.018). Compared with placebo, donepezil was
      associated with significant improvement in several cognitive domains, including
      working memory, speed of information processing, and visual learning and memory
      (P<=0.008). The results of the present study suggest that adjunctive use of
      donepezil is beneficial for improving cognitive function in patients with
      schizophrenia. 

PMID- 25075191
TI  - Dimensional assessment of DSM-5 social anxiety symptoms among university students
      and its relationship with functional impairment.
AB  - Social anxiety disorder is a common condition often associated with severe
      impairment in educational career. The aim of this paper was to evaluate
      prevalence rates and correlates of mild, moderate, and severe forms of social
      anxiety spectrum in a large sample of university students. Overall, 717
      university students were assessed with the Social Anxiety Spectrum Self-Report
      questionnaire. Using two cut-off scores, 61.4% of subjects were classified as low
      scorers, 10% as medium scorers, and 28.6% as high scorers. Both high and medium
      scorers reported fears related to social situations. Interpersonal sensitivity
      and specific phobias were more common among women with low scores.
      Childhood/adolescence social anxiety features were more common among males with
      medium scores. Behavioral inhibition was more common among males with high
      scores. Functional impairment was severe among high scorers and, to a lesser
      extent, among medium scorers. Social anxiety spectrum is largely represented
      among university students. Future studies should investigate whether sufferers of
      social phobia underachieve or end their professional objectives prematurely. 

PMID- 25075189
TI  - Sensory disturbances, inhibitory deficits, and the P50 wave in schizophrenia.
AB  - Sensory gating disturbances in schizophrenia are often described as an inability
      to filter redundant sensory stimuli that typically manifest as inability to gate
      neuronal responses related to the P50 wave, characterizing a decreased ability of
      the brain to inhibit various responses to insignificant stimuli. It implicates
      various deficits of perceptual and attentional functions, and this inability to
      inhibit, or "gate", irrelevant sensory inputs leads to sensory and information
      overload that also may result in neuronal hyperexcitability related to
      disturbances of habituation mechanisms. These findings seem to be particularly
      important in the context of modern electrophysiological and neuroimaging data
      suggesting that the filtering deficits in schizophrenia are likely related to
      deficits in the integrity of connections between various brain areas. As a
      consequence, this brain disintegration produces disconnection of information,
      disrupted binding, and disintegration of consciousness that in terms of modern
      neuroscience could connect original Bleuler's concept of "split mind" with
      research of neural information integration. 

PMID- 25075192
TI  - Lower extremity amputation in peripheral artery disease: improving patient
      outcomes.
AB  - Peripheral artery disease affects over eight million Americans and is associated
      with an increased risk of mortality, cardiovascular disease, functional
      limitation, and limb loss. In its most severe form, critical limb ischemia,
      patients are often treated with lower extremity (LE) amputation (LEA), although
      the overall incidence of LEA is declining. In the US, there is significant
      geographic variation in the performing of major LEA. The rate of death after
      major LEA in the US is approximately 48% at 1 year and 71% at 3 years. Despite
      this significant morbidity and mortality, the use of diagnostic testing (both
      noninvasive and invasive testing) in the year prior to LEA is low and varies
      based on patient, provider, and regional factors. In this review we discuss the
      significance of LEA and methods to reduce its occurrence. These methods include
      improved recognition of the risk factors for LEA by clinicians and patients,
      strong advocacy for noninvasive and/or invasive imaging prior to LEA, improved
      endovascular revascularization techniques, and novel therapies. 

PMID- 25075193
TI  - Public attitudes about lung cancer: stigma, support, and predictors of support.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer death, yet public
      engagement with efforts against lung cancer is low. Public engagement with a
      cancer is critical to efforts to combat it, yet the reasons for low support for
      efforts against lung cancer have not been systematically characterized. METHODS:
      We conducted a telephone survey of 1,071 people to determine levels of engagement
      and attitudes that might potentially drive engagement. These were then analyzed
      by univariate and multivariate analysis. RESULTS: Eight percent of participants
      were involved with a lung cancer organization and 12% chose it among cancers to
      receive more support. Most participants felt that lung cancer was principally
      caused by external factors, that it could be cured if caught early, and that lung
      cancer patients were at least partly to blame for their illness. In multivariate
      analysis, participants who were supportive in some way of efforts against lung
      cancer were more likely to be employed, live in suburbia, and to be unsure of the
      cause of lung cancer. Potential supporters were more likely to be employed,
      female, younger, have higher income, to believe that genetics is the primary
      cause of lung cancer, and to believe that lung cancer can be cured when caught
      early. Participants frequently noted that they supported a particular cancer
      because of knowing someone affected by that cancer. CONCLUSION: As the lung
      cancer movement attempts to grow and increase its impact, the most successful
      recruitment efforts will be targeted to these groups.

PMID- 25075194
TI  - Multidisciplinary rehabilitation can impact on health-related quality of life
      outcome in radical cystectomy: secondary reported outcome of a randomized
      controlled trial.
AB  - PURPOSE: Health related quality of life (HRQoL) is an important outcome in cancer
      care, although it is not well reported in surgical uro-oncology. Radical
      cystectomy (RC) with lymph-node dissection is the standard treatment of muscle
      invasive bladder cancer and high-risk noninvasive bladder cancer. A wide range of
      impairments are reported postsurgery. The aims were to evaluate whether a
      standardized pre- and postoperative physical exercise program and enhanced
      mobilization can impact on HRQoL and inpatient satisfaction in RC, as defined by
      the European Organisation for Research and Treatment of Cancer (EORTC). MATERIALS
      AND METHODS: Patients were randomized to fast-track RC and intervention (nI=50)
      or fast-track standard treatment (nS=57). HRQoL and inpatient satisfaction was
      measured using valid questionnaires: EORTC Quality of Life Questionnaire Core 30
      (QLQ-C30) combined with the disease-specific EORTC BLS24 (baseline), and EORTC
      BLM30 (follow-up), and IN-PATSAT32 inpatient-satisfaction survey at discharge.
      Efficacy was defined as the differences in HRQoL-scores between treatment groups
      at the 4-month follow-up. RESULTS: The intervention group significantly improved
      HRQoL scores in dyspnea (P<=0.05), constipation (P<0.02), and abdominal
      flatulence (P<=0.05) compared to the standard group. In contrast, the standard
      group reported significantly reduced symptoms in sleeping pattern (P<=0.04) and
      clinically relevant differences in role function, body function, and fatigue. The
      intervention did not compromise inpatient satisfaction. CONCLUSION: We found no
      overall impact on global HRQoL due to a physical rehabilitation program. However,
      pre- and postoperative physical rehabilitation can significantly and positively
      impact on HRQoL aspects related to bowel management and respiratory function
      (dyspnea) without compromising inpatient satisfaction. These results highlight
      the role of multimodal rehabilitation, including physical exercises in fast-track
      RC.

PMID- 25075195
TI  - Costs and health care resource utilization among chronic obstructive pulmonary
      disease patients with newly acquired pneumonia.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at
      increased risk for lung infections and other pathologies (eg, pneumonia);
      however, few studies have evaluated the impact of pneumonia on health care
      resource utilization and costs in this population. The purpose of this study was
      to estimate health care resource utilization and costs among COPD patients with
      newly acquired pneumonia compared to those without pneumonia. METHODS: A
      retrospective claims analysis using Truven MarketScan((r)) Commercial and
      Medicare databases was conducted. COPD patients with and without newly acquired
      pneumonia diagnosed between January 1, 2004 and September 30, 2011 were
      identified. Propensity score matching was used to create a 1:1 matched cohort.
      Patient demographics, comorbidities (measured by Charlson Comorbidity Index), and
      medication use were evaluated before and after matching. Health care resource
      utilization (ie, hospitalizations, emergency room [ER] and outpatient visits),
      and associated health care costs were assessed during the 12-month follow-up.
      Logistic regression was conducted to evaluate the risk of hospitalization and ER
      visits, and gamma regression models and two-part models compared health care
      costs between groups after matching. RESULTS: In the baseline cohort (N=467,578),
      patients with newly acquired pneumonia were older (mean age: 70 versus [vs] 63
      years) and had higher Charlson Comorbidity Index scores (3.3 vs 2.6) than
      patients without pneumonia. After propensity score matching, the pneumonia cohort
      was nine times more likely to have a hospitalization (odds ratio; 95% confidence
      intervals [CI] =9.2; 8.9, 9.4) and four times more likely to have an ER visit
      (odds ratio; 95% CI =4.4; 4.3, 4.5) over the 12-month follow-up period compared
      to the control cohort. The estimated 12-month mean hospitalization costs ($14,353
      [95% CI: $14,037-$14,690]), outpatient costs ($6,891 [95% CI: $6,706-$7,070]),
      and prescription drug costs ($1,104 [95% CI: $1,054-$1,142]) were higher in the
      pneumonia cohort than in the control cohort. CONCLUSION: This study demonstrated
      elevated health care resource use and costs in patients with COPD after acquiring
      pneumonia compared to those without pneumonia.

PMID- 25075196
TI  - Oncology drug health technology assessment recommendations: Canadian versus UK
      experiences.
AB  - BACKGROUND: CANADA HAS TWO HEALTH TECHNOLOGY ASSESSMENT (HTA) AGENCIES
      RESPONSIBLE FOR ONCOLOGY DRUG FUNDING RECOMMENDATIONS: the Institut National
      d'Excellence en Sante et Services Sociaux (INESSS) for the province of Quebec and
      the pan-Canadian Oncology Drug Review for the rest of Canada. The objective of
      the research was to review and compare the recommendations of these two agencies
      alongside an international comparator - the National Institute for Health and
      Care Excellence (NICE) in the United Kingdom - with respect to their
      recommendations records and the influence of clinical and cost-effectiveness
      evidence on the recommendations. METHODS: Recommendations were identified from
      the three agencies from January 1, 2002 to June 1, 2013. Recommendations were
      limited to five cancer sites (lung, breast, colon, kidney, blood) and to
      metastatic/advanced settings. Descriptive analyses examined the frequency of
      positive recommendations and factors related to a positive recommendation. For
      each recommendation, only publicly available information posted on the agency
      website was used to abstract data. RESULTS: There was a wide variation in the
      rate of positive recommendations, ranging from 48% for NICE to 95% for Canada's
      national process (among the 74% of its recommendations that were publicly
      posted). Interagency agreement was low, with full agreement for only six of the
      14 drugs commonly reviewed by all three agencies. Evidence of a survival gain was
      not necessary for a positive recommendation; progression-free survival was
      acceptable. Different approaches were taken when addressing unacceptable cost
      effectiveness. NICE was most likely to yield a negative recommendation on these
      grounds, whereas Canada's national process was most likely to yield a positive
      recommendation with a required pricing arrangement. CONCLUSION: In this analysis,
      the primary reason for the observed divergence between agency recommendations
      appeared to be the availability of mechanisms in each jurisdiction to address
      cost-effectiveness subsequent to the HTA assessment process. Furthermore, caution
      is needed when interpreting cross-agency comparisons between HTA agencies, as
      recommendations may not correspond directly to subsequent funding decisions and
      actual patient access. This may be a concern, given the high international
      profile of assessments conducted by the reviewed HTA agencies.

PMID- 25075197
TI  - Effect of plant extracts on H2O2-induced inflammatory gene expression in
      macrophages.
AB  - BACKGROUND: Arctium lappa (AL), Camellia sinensis (CS), Echinacea angustifolia,
      Eleutherococcus senticosus, Panax ginseng (PG), and Vaccinium myrtillus (VM) are
      plants traditionally used in many herbal formulations for the treatment of
      various conditions. Although they are well known and already studied for their
      anti-inflammatory properties, their effects on H2O2-stimulated macrophages are a
      novel area of study. MATERIALS AND METHODS: Cell viability was tested after
      treatment with increasing doses of H2O2 and/or plant extracts at different times
      of incubation to identify the optimal experimental conditions. The messenger
      (m)RNA expression of TNFalpha, COX2, IL1beta, NFkappaB1, NFkappaB2, NOS2, NFE2L2,
      and PPARgamma was analyzed in macrophages under H2O2 stimulation. The same genes
      were also quantified after plant extract treatment on cells pre-stimulated with
      H2O2. RESULTS: A noncytotoxic dose (200 MUM) of H2O2 induced active mRNA
      expression of COX2, IL1beta, NFE2L2, NFkappaB1, NFkappaB2, NOS2, and TNFalpha,
      while PPARgamma was depressed. The expression of all genes tested was
      significantly (P<0.001) regulated by plant extracts after pre-stimulation with
      H2O2. COX2 was downregulated by AL, PG, and VM. All extracts depressed IL1beta
      expression, but upregulated NFE2L2. NFkappaB1, NFkappaB2, and TNFalpha were
      downregulated by AL, CS, PG, and VM. NOS2 was inhibited by CS, PG, and VM.
      PPARgamma was decreased only after treatment with E. angustifolia and E.
      senticosus. CONCLUSION: The results of the present study indicate that the
      stimulation of H2O2 on RAW267.4 cells induced the transcription of
      proinflammatory mediators, showing that this could be an applicable system by
      which to activate macrophages. Plant extracts from AL, CS, PG, and VM possess in
      vitro anti-inflammatory activity on H2O2-stimulated macrophages by modulating key
      inflammation mediators. Further in vitro and in vivo investigation into molecular
      mechanisms modulated by herbal extracts should be undertaken to shed light on the
      development of novel modulating therapeutic strategies.

PMID- 25075198
TI  - Inflammatory bowel disease: clinical aspects and treatments.
AB  - Inflammatory bowel disease (IBD) is defined as a chronic intestinal inflammation
      that results from host-microbial interactions in a genetically susceptible
      individual. IBDs are a group of autoimmune diseases that are characterized by
      inflammation of both the small and large intestine, in which elements of the
      digestive system are attacked by the body's own immune system. This inflammatory
      condition encompasses two major forms, known as Crohn's disease and ulcerative
      colitis. Patients affected by these diseases experience abdominal symptoms,
      including diarrhea, abdominal pain, bloody stools, and vomiting. Moreover,
      defects in intestinal epithelial barrier function have been observed in a number
      of patients affected by IBD. In this review, we first describe the types and
      symptoms of IBD and investigate the role that the epithelial barrier plays in the
      pathophysiology of IBD as well as the major cytokines involved. We then discuss
      steps used to diagnose this disease and the treatment options available, and
      finally provide an overview of the recent research that aims to develop new
      therapies for such chronic disorders. 

PMID- 25075200
TI  - A pilot study comparing the DuoFertility((r)) monitor with ultrasound in
      infertile women.
AB  - BACKGROUND: The purpose of this study was to assess the accuracy of ovulation
      detection by the DuoFertility((r)) monitor compared with transvaginal ultrasound
      in infertile women with regular menstrual cycles. METHODS: Eight infertile
      patients, aged 27-40 years, with a body mass index of 19-29, regular menses,
      normal ovaries on pelvic ultrasound scan, and normal early follicular luteinizing
      hormone (LH), follicle-stimulating hormone, and prolactin were recruited from
      infertility clinics in primary and secondary care for this pilot, prospective,
      observational study. The patients were asked to use the DuoFertility monitor for
      the whole cycle, with investigators and patients blind to DuoFertility data.
      Daily urine LH monitoring commenced on cycle day 8, with daily transvaginal
      ultrasound following the first positive LH until ovulation was observed.
      Ovulation was further confirmed by serum progesterone. The main outcome measure
      was detection of ovulation by the DuoFertility monitor, and correlation between
      day of ovulation assessed by DuoFertility and ultrasound. RESULTS: DuoFertility
      identified ovulation as having occurred within one day of that determined via
      ultrasound in all cycles. The sensitivity of ovulation detection was 100% (95%
      confidence interval 82-100). The specificity could not be concluded from the
      data. CONCLUSION: In infertile women with regular cycles, the DuoFertility
      monitor appears to accurately identify ovulatory cycles and the day of ovulation.

PMID- 25075199
TI  - Patients with chronic pain lack somatic markers during decision-making.
AB  - Patients with chronic pain have impaired cognitive functions, including decision
      making, as shown with the Iowa gambling task (IGT). The main aim of this study
      was to elucidate whether patients' decision making is associated with a lack of
      the anticipatory skin conductance response (SCR). An increase in anticipatory SCR
      before making unfavorable choices is known to guide decisions in healthy controls
      during the IGT. Since several brain regions involved in decision making are
      reported to have altered morphology in patients with chronic pain, the second aim
      was to explore the associations between IGT performance and brain structure
      volumes. Eighteen patients with chronic pain of mixed etiology and 19 healthy
      controls matched in terms of age, sex, and education were investigated with a
      computerized IGT during the recording of SCR, heart rate, and blood pressure. The
      participants also underwent neuropsychological testing, and three-dimensional T1
      weighted cerebral magnetic resonance images were obtained. Contrary to controls,
      patients did not generate anticipatory SCRs before making unfavorable choices,
      and they switched between decks of cards during the late phase of the IGT
      significantly more often, and this was still observed after adjusting for
      depression scores. None of the other autonomic measures differed during IGT
      performance in either group or between groups. In patients, IGT scores correlated
      positively with total cortical grey matter volume. In controls, there was no such
      association, but their IGT scores correlated with the anticipatory SCR. It may be
      speculated that the reduction in anticipatory SCRs makes the chronic pain
      patients rely more on cortical resources during decision making. 

PMID- 25075201
TI  - The burden of unintended pregnancies in Brazil: a social and public health system
      cost analysis.
AB  - BACKGROUND: Unintended pregnancy (UP) is an unmet medical need with consequences
      worldwide. We evaluate the costs of UP based on pregnancies in Brazil from for
      the year 2010. METHODS: The consequences of UP were evaluated using decision
      analysis based on pregnancy rates and outcomes as miscarriage, induced abortion,
      and live birth, which were factored into the analysis. The model discriminated
      between maternal and child outcomes and accounted for costs (in Brazilian
      currency [Real$, R$]) within the Brazilian public health service attributed to
      preterm birth, neonatal admission, cerebral palsy, and neonatal and maternal
      mortality. Event probabilities were obtained from local resources. RESULTS: We
      estimate that 1.8 million UPs resulted in 159,151 miscarriages, 48,769 induced
      abortions, 1.58 million live births, and 312 maternal deaths, including ten (3%)
      attributed to unsafe abortions. The total estimated costs attributed to UP are
      R$4.1 billion annually, including R$32 million (0.8%) and R$4.07 billion (99.2%)
      attributed to miscarriages and births and complications, respectively. Direct
      birth costs accounted for approximately R$1.22 billion (30.0%), with labor and
      delivery responsible for most costs (R$988 million; 24.3%) for the year 2010. The
      remainder of costs were for infant complications (R$2.84 billion; 72.3%) with
      hospital readmission during the first year accounting for approximately R$2.15
      billion (52.9%). Based on the national cost, we estimate the cost per UP to be
      R$2,293. CONCLUSION: Despite weaknesses in precise estimates in annual
      pregnancies and induced abortions, our estimates reflect the costs of UP for
      different pregnancy outcomes. The main costs associated with UP are in those
      carried to parturition. The health cost of abortion represents a small proportion
      of total costs as these are paid for outside of the public health system.
      Consequently, reductions in UP will generate not only cost savings, but
      reductions in woman and child morbidity and mortality.

PMID- 25075202
TI  - What works in 'real life' to facilitate home deaths and fewer hospital admissions
      for those at end of life?: results from a realist evaluation of new palliative
      care services in two English counties.
AB  - BACKGROUND: WE EVALUATED END OF LIFE CARE SERVICES IN TWO ENGLISH COUNTIES
      INCLUDING: coordination centres, telephone advice line, 'Discharge in Reach'
      nurses, a specialist community personal care team and community nurse educators.
      Elsewhere, we published findings detailing high family carer satisfaction and
      fewer hospital admissions, Accident and Emergency attendances and hospital deaths
      for service users compared to controls. The aim of this paper is to discuss what
      contributed to those outcomes. METHODS: Using realist evaluation, data collection
      included documentation (e.g. referral databases), 15 observations of services and
      interviews with 43 family carers and 105 professionals. Data were analysed using
      framework analysis, applying realist evaluation concepts. Findings were discussed
      at successive team meetings and further data was collected until team consensus
      was reached. RESULTS: Services 'worked' primarily for those with cancer with
      'fast track' funding who were close to death. Factors contributing to success
      included services staffed with experienced palliative care professionals with
      dedicated (and sufficient) time for difficult conversations with family carers,
      patients and/or clinical colleagues about death and the practicalities of caring
      for the dying. Using their formal and informal knowledge of the local healthcare
      system, they accessed community resources to support homecare and delivered
      excellent services. This engendered confidence and reassurance for staff, family
      carers and patients, possibly contributing to less hospital admissions and A&E
      attendances and more home deaths. CONCLUSIONS: With demand for 24-hour end of
      life care growing and care provision fragmented across health and social care
      boundaries, services like these that cut across organisational sectors may become
      more important. They offer an overview to help navigate those desiring a home
      death through the system.

PMID- 25075204
TI  - Automated quantitative multiplex immunofluorescence in situ imaging identifies
      phospho-S6 and phospho-PRAS40 as predictive protein biomarkers for prostate
      cancer lethality.
AB  - BACKGROUND: We have witnessed significant progress in gene-based approaches to
      cancer prognostication, promising early intervention for high-risk patients and
      avoidance of overtreatment for low-risk patients. However, there has been less
      advancement in protein-based approaches, even though perturbed protein levels and
      post-translational modifications are more directly linked with phenotype. Most
      current, gene expression-based platforms require tissue lysis resulting in loss
      of structural and molecular information, and hence are blind to tumor
      heterogeneity and morphological features. RESULTS: Here we report an automated,
      integrated multiplex immunofluorescence in situ imaging approach that
      quantitatively measures protein biomarker levels and activity states in defined
      intact tissue regions where the biomarkers of interest exert their phenotype.
      Using this approach, we confirm that four previously reported prognostic markers,
      PTEN, SMAD4, CCND1 and SPP1, can predict lethal outcome of human prostate cancer.
      Furthermore, we show that two PI3K pathway-regulated protein activities, pS6
      (RPS6-phosphoserines 235/236) and pPRAS40 (AKT1S1-phosphothreonine 246),
      correlate with prostate cancer lethal outcome as well (individual marker hazard
      ratios of 2.04 and 2.03, respectively). Finally, we incorporate these 2 markers
      into a novel 5-marker protein signature, SMAD4, CCND1, SPP1, pS6, and pPRAS40,
      which is highly predictive for prostate cancer-specific death. The ability to
      substitute PTEN with phospho-markers demonstrates the potential of quantitative
      protein activity state measurements on intact tissue. CONCLUSIONS: In summary,
      our approach can reproducibly and simultaneously quantify and assess multiple
      protein levels and functional activities on intact tissue specimens. We believe
      it is broadly applicable to not only cancer but other diseases, and propose that
      it should be well suited for prognostication at early stages of pathogenesis
      where key signaling protein levels and activities are perturbed.

PMID- 25075203
TI  - Colorectal cancer derived organotypic spheroids maintain essential tissue
      characteristics but adapt their metabolism in culture.
AB  - BACKGROUND: Organotypic tumor spheroids, a 3D in vitro model derived from patient
      tumor material, preserve tissue heterogeneity and retain structural tissue
      elements, thus replicating the in vivo tumor more closely than commonly used 2D
      and 3D cell line models. Such structures harbour tumorigenic cells, as revealed
      by xenograft implantation studies in animal models and maintain the genetic
      makeup of the original tumor material. The aim of our work was a morphological
      and proteomic characterization of organotypic spheroids derived from colorectal
      cancer tissue in order to get insight into their composition and associated
      biology. RESULTS: Morphological analysis showed that spheroids were of about 250
      MUm in size and varied in structure, while the spheroid cells differed in shape
      and size and were tightly packed together by desmosomes and tight junctions. Our
      proteomic data revealed significant alterations in protein expression in
      organotypic tumor spheroids cultured as primary explants compared to primary
      colorectal cancer tissue. Components underlying cellular and tissue architecture
      were changed; nuclear DNA/ chromatin maintenance systems were up-regulated,
      whereas various mitochondrial components were down-regulated in spheroids. Most
      interestingly, the mesenchymal cells appear to be substantial component in such
      cellular assemblies. Thus the observed changes may partly occur in this cellular
      compartment. Finally, in the proteomics analysis stem cell-like characteristics
      were observed within the spheroid cellular assembly, reflected by accumulation of
      Alcam, Ctnnb1, Aldh1, Gpx2, and CD166. These findings were underlined by IHC
      analysis of Ctnnb1, CD24 and CD44, therefore warranting closer investigation of
      the tumorigenic compartment in this 3D culture model for tumor tissue.
      CONCLUSIONS: Our analysis of organotypic CRC tumor spheroids has identified
      biological processes associated with a mixture of cell types and states,
      including protein markers for mesenchymal and stem-like cells. This 3D tumor
      model in which tumor heterogeneity is preserved may represent an advantageous
      model system to investigate novel therapeutic approaches.

PMID- 25075206
TI  - Autologous or heterologous fibrin sealant scaffold: which is the better choice?

PMID- 25075205
TI  - Developing a provisional, international minimal dataset for Juvenile
      Dermatomyositis: for use in clinical practice to inform research.
AB  - BACKGROUND: Juvenile dermatomyositis (JDM) is a rare but severe autoimmune
      inflammatory myositis of childhood. International collaboration is essential in
      order to undertake clinical trials, understand the disease and improve long-term
      outcome. The aim of this study was to propose from existing collaborative
      initiatives a preliminary minimal dataset for JDM. This will form the basis of
      the future development of an international consensus-approved minimum core
      dataset to be used both in clinical care and inform research, allowing
      integration of data between centres. METHODS: A working group of internationally
      representative JDM experts was formed to develop a provisional minimal dataset.
      Clinical and laboratory variables contained within current national and
      international collaborative databases of patients with idiopathic inflammatory
      myopathies were scrutinised. Judgements were informed by published literature and
      a more detailed analysis of the Juvenile Dermatomyositis Cohort Biomarker Study
      and Repository, UK and Ireland. RESULTS: A provisional minimal JDM dataset has
      been produced, with an associated glossary of definitions. The provisional
      minimal dataset will request information at time of patient diagnosis and during
      on-going prospective follow up. At time of patient diagnosis, information will be
      requested on patient demographics, diagnostic criteria and treatments given prior
      to diagnosis. During on-going prospective follow-up, variables will include the
      presence of active muscle or skin disease, major organ involvement or
      constitutional symptoms, investigations, treatment, physician global assessments
      and patient reported outcome measures. CONCLUSIONS: An internationally agreed
      minimal dataset has the potential to significantly enhance collaboration, allow
      effective communication between groups, provide a minimal standard of care and
      enable analysis of the largest possible number of JDM patients to provide a
      greater understanding of this disease. This preliminary dataset can now be
      developed into a consensus-approved minimum core dataset and tested in a wider
      setting with the aim of achieving international agreement.

PMID- 25075207
TI  - Growth hormone significantly increases the adult height of children with
      idiopathic short stature: comparison of subgroups and benefit.
AB  - BACKGROUND: Children with Idiopathic Short Stature do not attain a normal adult
      height. The improvement of adult height with treatment with recombinant human
      growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually
      less that 4 cm, and they remain short as adults. The benefit obtained seems dose
      dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of
      0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has
      remained controversial. OBJECTIVE: The objective was to conduct a retrospective
      analysis of our experience with 123 children with ISS treated with 0.32 +/- 0.03
      mg/kg/week of rhGH, with the aim of comparing the different subgroups of non
      familial short stature, familial short stature, normal puberty, and delayed
      puberty and to assess the benefit by comparison with 305 untreated historical
      controls, from nine different randomized and nonrandomized controlled studies.
      RESULTS: Eighty eight of our children (68 males and 20 females) attained an adult
      height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with
      a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm
      (6.7 to 10.5 cm) for females. In the analysis of the subgroups, the adult height
      and adult height gain of children with non-familial short stature were
      significantly higher than of familial short stature. No difference was found in
      the cohorts with normal or delayed puberty in any of the subgroups, except
      between the non-familial short stature and familial short stature puberty
      cohorts. This has implications for the interpretation of the benefit of treatment
      in studies where the number of children with familial short stature in the
      controls or treated subjects is not known. The treatment was safe. There were no
      significant adverse events. The IGF-1 values were essentially within the levels
      expected for the stages of puberty. CONCLUSION: Our experience was quite positive
      with normalization of the heights and growth of the children during childhood and
      the attainment of normal adult heights, the main two aims of treatment.

PMID- 25075208
TI  - Evaluation of an apparatus to be combined with a smartphone for the early
      detection of spinal deformities.
AB  - BACKGROUND: Mobile smartphones are equipped with inclinometers enabling them to
      acquire angular clinical measures. The Scolioscreen has been developed in
      conjunction with a smartphone APP to enable the measure of the angle of trunk
      inclination (ATI) thus offering a convenient and reliable means to measure and
      screen for spinal deformities. The objective was to compare the reliability and
      accuracy of a Scolioscreen-smartphone combination, a smartphone alone, and a
      Scoliometer, for measuring the angle of trunk inclination in spinal deformities
      under blinded conditions for intra- and inter-observer analyses. METHODS: A
      cohort of 39 patients with adolescent idiopathic scoliosis were recruited. Each
      had maximum ATI measured by 3 observers: attending spine surgeon, nurse, and
      parent presenting with patient. Two series of measurements were performed by each
      observer using Scolioscreen-smartphone, smartphone alone and Scoliometer. Intra
      class correlation coefficients (ICC) from two-way mixed model based on absolute
      agreement were used to assess intra- and inter-observer reliability as well as
      consistency between measurement techniques. RESULTS: Intra- and inter-observer
      reliability for measuring maximum ATI was 0.94-0.89 with Scolioscreen-smartphone,
      decreased to 0.89-0.75 for smartphone alone, and was 0.95- 0.89 for Scoliometer.
      Considering Scoliometer measurement taken by surgeon the gold standard, there was
      excellent consistency with measurements from Scolioscreen-smartphone taken by
      surgeon (ICC = 0.99), nurse (ICC = 0.95), and parent (ICC = 0.91). Conversely,
      consistency decreased when surgeon (ICC = 0.86), nurse (ICC = 0.86) and parent
      (ICC = 0.85) used smartphone alone. CONCLUSION: Study shows the Scolioscreen
      smartphone to overcome limitations associated with ATI measurements using
      smartphones alone. The Scolioscreen-smartphone provides a reliability and
      consistency similar to the gold standard (use of Scoliometer by spine surgeon)
      and enables a parent to take reliable measurements on their own thus offering an
      accessible and convenient tool for all to use.

PMID- 25075210
TI  - MDM2 polymorphism associated with the development of cervical lesions in women
      infected with Human papillomavirus and using of oral contraceptives.
AB  - BACKGROUND: The MDM2 gene is the major negative regulator of p53, a tumor
      suppressor protein. Single nucleotide polymorphism in promoter region of MDM2
      gene leads to increased expression resulting in higher levels of MDM2 protein.
      This event increases the attenuation of the p53 pathway. Polymorphisms in this
      gene can interfere in the regulation of cellular proliferation. We evaluated
      whether MDM2 SNP309 (rs2278744) associated or not with the use of oral
      contraceptive can heighten susceptibility to development of cervical lesions in
      women HPV infected. METHODS: MDM2 SNP309 (rs2278744) was genotyped in a total of
      287 patients using the PCR-RFLP technique. The results were analyzed by UNPHASED
      v.3.121 and SNPStats programs. RESULTS: The three groups (SIL, LSIL and HSIL)
      showed no significant differences in either genotype or allelic frequencies for
      MDM2 polymorphisms, except when HSIL was compared with LSIL (p = 0.037; OR =
      1.81). Furthermore, in the analysis of contraceptives, a significant association
      was found between the use of contraceptives and the MDM2 variant in the
      development of high-grade cervical lesions for the TG genotype (p = 0.019; OR =
      2.21) when HSIL was compared with control. When HSIL was compared with LSIL (p =
      0.006; OR = 2.27). CONCLUSION: The results of this study suggest that MDM2 SNP309
      might be a good marker for assessing the progression of LSIL to HSIL. In
      addition, they also show that oral contraceptives alone, did not have any effect
      on the progression or development of cervical lesions. However, they may act
      synergistically with MDM2 SNP309 (rs2278744) and HPV infection in the development
      of cervical lesions.

PMID- 25075209
TI  - Loss of nuclear PTEN in HCV-infected human hepatocytes.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a major risk factor for chronic
      hepatitis and hepatocellular carcinoma (HCC); however, the mechanism of HCV
      mediated hepatocarcinogenesis is not well understood. Insufficiency of PTEN tumor
      suppressor is associated with more aggressive cancers, including HCC. We asked
      whether viral non-coding RNA could initiate oncogenesis in HCV infected human
      hepatocytes. The results presented herein suggest that loss of nuclear PTEN in
      HCV-infected human hepatocytes results from depletion of Transportin-2, which is
      a direct target of viral non-coding RNA, vmr11. METHODS: The intracellular
      distribution of PTEN in HCV-infected cells was monitored by immunostaining and
      Western blots of nuclear and cytoplasmic proteins. Effects of PTEN depletion were
      examined by comparing expression arrays of uninfected cells with either HCV
      infected or vmr11-transfected cells. Target genes suggested by array analyses
      were validated by Western blot. The influence of nuclear PTEN deficiency on virus
      production was determined by quantitative analysis of HCV genomic RNA in culture
      media of infected hepatocytes. RESULTS: Import of PTEN to the nucleus relies on
      the interaction of Transportin-2 and PTEN proteins; we show that depletion of
      Transportin-2 by HCV infection or by the introduction of vmr11 in uninfected
      cells results in reduced nuclear PTEN. In turn, nuclear PTEN insufficiency
      correlates with increased virus production and the induction of gamma-H2AX, a
      marker of DNA double-strand breaks and genomic instability. CONCLUSION: An HCV
      derived small non-coding RNA inhibits Transportin-2 and PTEN translocation to the
      nucleus, suggesting a direct viral role in hepatic oncogenesis.

PMID- 25075211
TI  - Effects of gender, age, family support, and treatment on perceived stress and
      coping of patients with type 2 diabetes mellitus.
AB  - BACKGROUND: We previously found that the empowerment of patients with type 2
      diabetes mellitus can be strongly affected by gender and age in addition to self
      managed diet and exercise behaviors and treatment. This study was to examine the
      effects of gender, age, family support, and treatment on the perceived stress and
      coping of patients with type 2 diabetes mellitus living with family. METHODS: A
      survey was conducted of 140 adults with type 2 diabetes mellitus who were living
      with family. There was no significant difference in hemoglobin A1c (HbA1c)
      between male and female. Perceived stress and coping were measured with the
      Japanese version of the Appraisal of Diabetes Scale and the Lazarus Type Stress
      Coping Inventory. Stepwise regression analysis and path analysis were performed
      to identify factors that affect the perceived stress and coping of patients.
      RESULTS: (1) Perceived stress and coping were strongly affected by gender. (2)
      Perceived stress and coping were affected by age for males, but perceived stress
      was not affected by age for females. However, females showed a greater
      "psychological impact of diabetes" than did males. Females aged between 50 and 69
      years engaged in active problem solving, but awareness of diabetes was low. (3)
      Treatment regimens had an effect on HbA1c for both sexes, and diet therapy
      affected the awareness of diabetes of males and coping of females. (4) For
      females, "sense of self-control" was strongly associated with coping, and those
      who were living with non-spouse family members had a greater psychological impact
      of diabetes than those living with only their spouse. (5) For males, coping was
      strongly affected by living with their spouse. CONCLUSIONS: The results suggest
      that perceived stress, coping, and diet regimen are deeply associated with gender
      and age and that a male with type 2 diabetes mellitus living with his spouse is
      strongly dependent on support from the spouse. It is important to take into
      account gender, age, and family environment to provide patients with an
      individualized approach to addressing perceived stress and to provide education
      program for coping that can maximize treatment and maintain better, continuous
      glycemic control.

PMID- 25075212
TI  - A window of opportunity for reform in post-conflict settings? The case of Human
      Resources for Health policies in Sierra Leone, 2002-2012.
AB  - BACKGROUND: It is recognized that decisions taken in the early recovery period
      may affect the development of health systems. Additionally, some suggest that the
      immediate post-conflict period may allow for the opening of a political 'window
      of opportunity' for reform. For these reasons, it is useful to reflect on the
      policy space that exists in this period, by what it is shaped, how decisions are
      made, and what are their long-term implications. Examining the policy trajectory
      and its determinants can be helpful to explore the specific features of the post
      conflict policy-making environment. With this aim, the study looks at the
      development of policies on human resources for health (HRH) in Sierra Leone over
      the decade after the conflict (2002-2012). METHODS: Multiple sources were used to
      collect qualitative data on the period between 2002 and 2012: a stakeholder
      mapping workshop, a document review and a series of key informant interviews. The
      analysis draws from political economy and policy analysis tools, focusing on the
      drivers of reform, the processes, the contextual features, and the actors and
      agendas. FINDINGS: Our findings identify three stages of policy-making. At first
      characterized by political uncertainty, incremental policies and stop-gap
      measures, the context substantially changed in 2009. The launch of the Free
      Health Care Initiative provided to be an instrumental event and catalyst for
      health system, and HRH, reform. However, after the launch of the initiative, the
      pace of HRH decision-making again slowed down. CONCLUSIONS: OUR STUDY IDENTIFIES
      THE KEY DRIVERS OF HRH POLICY TRAJECTORY IN SIERRA LEONE: (i) the political
      situation, at first uncertain and later on more defined; (ii) the availability of
      funding and the stances of agencies providing such funds; (iii) the sense of need
      for radical change - which is perhaps the only element related to the post
      conflict setting. It also emerges that a 'windows of opportunity' for reform did
      not open in the immediate post-conflict, but rather 8 years later when the Free
      Health Care Initiative was announced, thus making it difficult to link it
      directly to the features of the post-conflict policy-making environment.

PMID- 25075214
TI  - Report from the Melanoma Independent Board First Melanoma MIB Conference, 21-22
      October 2013.
AB  - The Melanoma Independent Board (MIB) held its first conference from 21 to 22
      October, 2013, in Rome, Italy. Like the MIB itself, the conference brought
      together specialists from all aspects of cancer care: doctors, patient
      associations, journalists, and representatives from local government, hospitals,
      and pharma to encourage an interdisciplinary discussion on the future of
      melanoma. It was hoped that the conference would be an opportunity for all
      participants to see and understand each other's points of view. In memoriam of
      melanoma pioneer Natalie Cascinelli, the conference focussed on innovation and
      sustainability as well as the latest drug developments. 

PMID- 25075215
TI  - Adaptive immunity in cancer immunology and therapeutics.
AB  - The vast genetic alterations characteristic of tumours produce a number of tumour
      antigens that enable the immune system to differentiate tumour cells from normal
      cells. Counter to this, tumour cells have developed mechanisms by which to evade
      host immunity in their constant quest for growth and survival. Tumour-associated
      antigens (TAAs) are one of the fundamental triggers of the immune response. They
      are important because they activate, via major histocompatibility complex (MHC),
      the T cell response, an important line of defense against tumourigenesis.
      However, the persistence of tumours despite host immunity implies that tumour
      cells develop immune avoidance. An example of this is the up-regulation of
      inhibitory immune checkpoint proteins, by tumours, which induces a form of self
      tolerance. The majority of monoclonal antibodies in clinical practice have been
      developed to target tumour-specific antigens. More recently there has been
      research in the down-regulation of immune checkpoint proteins as a way of
      increasing anti-tumour immunity. 

PMID- 25075216
TI  - The Repurposing Drugs in Oncology (ReDO) Project.
AB  - The Repurposing Drugs in Oncology (ReDO) Project seeks to repurpose well-known
      and well-characterised non-cancer drugs for new uses in oncology. The rationale
      for this project is presented, examining current issues in oncological drug
      development, challenges for health systems, and existing and future patient
      needs. In addition to discussing the advantages of repurposing, the paper also
      outlines some of the characteristics used in the selection of drug candidates by
      this project. Challenges in moving candidate drugs into clinical trial and
      subsequent practice are also discussed. 

PMID- 25075217
TI  - Repurposing Drugs in Oncology (ReDO)-mebendazole as an anti-cancer agent.
AB  - Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti
      cancer properties that have been elucidated in a broad range of pre-clinical
      studies across a number of different cancer types. Significantly, there are also
      two case reports of anti-cancer activity in humans. The data are summarised and
      discussed in relation to suggested mechanisms of action. Based on the evidence
      presented, it is proposed that mebendazole would synergise with a range of other
      drugs, including existing chemotherapeutics, and that further exploration of the
      potential of mebendazole as an anti-cancer therapeutic is warranted. A number of
      possible combinations with other drugs are discussed in the Appendix. 

PMID- 25075218
TI  - A golden anniversary: highlights of the 50th annual meeting of the American
      Society of Clinical Oncology.
AB  - The 50th Annual Meeting of the American Society of Clinical Oncology showed a
      shift in the culture of cancer research, moving towards multidisciplinary,
      integrated, and patient-centric work. Hormone-sensitive cancers were particularly
      highlighted at this meeting, and impressive strides were made in the previously
      underserved areas of the lung and thyroid cancer. Interestingly, immunotherapy
      was one of the strongest themes to emerge. 

PMID- 25075219
TI  - An argument for discovery-driven research: from physicist to cancer researcher.

PMID- 25075220
TI  - Cancer and ageism.

PMID- 25075221
TI  - Recycling existing drugs for cancer therapy: delivering low cost cancer care.

PMID- 25075222
TI  - Applicability of the Clavien-Dindo classification to emergency surgical
      procedures: a retrospective cohort study on 444 consecutive patients.
AB  - BACKGROUND: Patients undergoing emergency surgery have a high risk for surgical
      complications and death. The Clavien-Dindo classification has been developed and
      validated in elective general surgical patients, but has not been validated in
      emergency surgical patients. The aim of the current study was to evaluate the
      Clavien-Dindo classification of surgical complications in emergency surgical
      patients and to study preoperative factors for risk stratification that should be
      included into a database of surgical complications. METHODS: A cohort of 444
      consecutive patients having emergency general surgery during a three-month period
      was retrospectively analyzed. Surgical complications were classified according to
      the Clavien-Dindo classification. Preoperative risk factors for complications
      were studied using logistic regression analysis. RESULTS: Preoperatively 37
      (8.3%) patients had organ dysfunctions. Emergency surgical patients required a
      new definition for Grade IV complications (organ dysfunctions). Only new onset
      organ dysfunctions or complications that significantly contributed to worsening
      of pre-operative organ dysfunctions were classified as grade IV complications.
      Postoperative complications developed in 115 (25.9%) patients, and 14 (3.2%)
      patients developed grade IV complication. Charlson comorbidity index,
      preoperative organ dysfunction and the type of surgery predicted postoperative
      complications. CONCLUSIONS: The Clavien-Dindo classification of surgical
      complications can be used in emergency surgical patients but preoperative organ
      dysfunctions should be taken into account when defining postoperative grade IV
      complications. For risk stratification patients' comorbidities, preoperative
      organ dysfunctions and the type of surgery should be taken into consideration.

PMID- 25075223
TI  - Single cell segmental aneuploidy detection is compromised by S phase.
AB  - BACKGROUND: Carriers of balanced translocations are at high risk for unbalanced
      gametes which can result in recurrent miscarriages or birth defects.
      Preimplantation genetic diagnosis (PGD) is often offered to select balanced
      embryos. This selection is currently mainly performed by array CGH on
      blastomeres. Current methodology does not take into account the phase of the cell
      cycle, despite the variable copy number status of different genomic regions in S
      phase. RESULTS: Cell lines derived from 3 patients with different chromosomal
      imbalances were used to evaluate the accuracy of single cell array CGH. The
      different cell cycle phases were sorted by flow cytometry and 10 single cells
      were picked per cell line per cell cycle phase, whole genome amplified and
      analyzed by BAC arrays, the most commonly used platform for PGD purposes. In
      contrast to G phase, where the imbalances were efficiently identified, less than
      half of the probes in the regions of interest indicated the presence of the
      aberration in 17 S-phase cells, resulting in reduced accuracy. CONCLUSIONS: The
      results demonstrate that the accuracy to detect segmental chromosomal imbalances
      is reduced in S-phase cells, which could be a source of misdiagnosis in PGD.
      Hence, the cell cycle phase of the analyzed cell is of great importance and
      should be taken into account during the analysis. This knowledge may guide future
      technological improvements.

PMID- 25075224
TI  - A comparison of hallux valgus angles assessed with computerised plantar pressure
      measurements, clinical examination and radiography in patients with diabetes.
AB  - BACKGROUND: Hallux valgus deformity is a common musculoskeletal foot disorder
      with a prevalence of 3.5% in adolescents to 35.7% in adults aged over 65 years.
      Radiographic measurements of hallux valgus angles (HVA) are considered to be the
      most reproducible and accurate assessment of HVA. However, in European countries,
      many podiatrists do not have direct access to radiographic facilities. Therefore,
      alternative measurements are desired. Such measurements are computerised plantar
      pressure measurement and clinical goniometry. The purpose of this study was to
      establish the agreement of these techniques and radiographic assessments.
      METHODS: HVA was determined in one hundred and eighty six participants suffering
      from diabetes. Radiographic measurements of HVA were performed with standardised
      static weight bearing dorsoplantar foot radiographs. The clinical goniometry for
      HVA was measured with a universal goniometer. Computerised plantar pressure
      measurement for HVA was executed with the EMED SF-4(r) pressure platform and
      Novel-Ortho-Geometry software. The intra-class correlation coefficients (ICC) and
      levels of agreement were analysed using Bland & Altman plots. RESULTS: Comparison
      of radiographic measurements to clinical goniometry for HVA showed an intraclass
      correlation coefficient (ICC) of 0.81 (95% confidence interval, 0.76 to 0.86;
      p<0.001). Radiographic measurement versus computerised plantar pressure
      measurement showed an ICC of 0.59 (95% confidence interval, 0.49 to 0.68;
      p<0.001). In addition, clinical goniometry versus computerised plantar pressure
      measurement showed an ICC of 0.77 (95% confidence interval, 0.70 to 0.82;
      p<0.001). The systematic difference of the computerised plantar pressure
      measurement compared with radiographic measurement and clinical goniometry was
      7.0 degrees (SD 6.8) and 5.2 degrees (SD 5.0), respectively. The systemic
      difference of radiographic measurements compared with clinical goniometry was 1.8
      degrees (SD 5.0). CONCLUSIONS: The agreement of computerised plantar pressure
      measurement and clinical goniometry for HVA compared to radiographic measurement
      of HVA is unsatisfactory. Radiographic measurements of HVA and clinical
      goniometry for HVA yield better agreement compared to radiographic measurements
      and computerised plantar pressure measurement. The traditional radiographic
      measurement techniques are strongly recommended for the assessment of HVA.

PMID- 25075225
TI  - Gene clusters of Hafnia alvei strain FB1 important in survival and pathogenesis:
      a draft genome perspective.
AB  - BACKGROUND: Hafnia alvei is an opportunistic pathogen involved in various types
      of nosocomical infections. The species has been found to inhabit food and
      mammalian guts. However, its status as an enteropathogen, and whether the food
      inhabiting strains could be a source of gastrointestinal infection remains
      obscure. In this report we present a draft genome of H. alvei strain FB1 isolated
      from fish paste meatball, a food popular among Malaysian and Chinese populations.
      The data was generated on the Illumina MiSeq platform. RESULTS: A comparative
      study was carried out on FB1 against two other previously sequenced H. alvei
      genomes. Several gene clusters putatively involved in survival and pathogenesis
      of H. alvei FB1 in food and gut environment were characterised in this study.
      These include the widespread colonisation island (WCI), the tad locus that is
      known to play an essential role in biofilm formation, a eut operon that might
      contribute to advantage in nutrient acquisition in gut environment, and genes
      responsible for siderophore production This features enable the bacteria to
      successful colonise in the host gut environment. CONCLUSION: With the whole
      genome data of H. alvei FB1 presented in this study, we hope to provide an
      insight into future studies on this candidate of enteropathogen by looking into
      the possible mechanisms employed to survive stresses and gain advantage in
      competitions, which eventually leads to successful colonisation and pathogenesis.
      This is to serve as the basis for more effective clinical diagnosis and
      treatment.

PMID- 25075227
TI  - Epigenetic response in mice mastitis: Role of histone H3 acetylation and
      microRNA(s) in the regulation of host inflammatory gene expression during
      Staphylococcus aureus infection.
AB  - BACKGROUND: There is renewed interest towards understanding the host-pathogen
      interaction in the light of epigenetic modifications. Although epithelial tissue
      is the major site for host-pathogen interactions, there is handful of studies to
      show how epithelial cells respond to pathogens. Bacterial infection in the
      mammary gland parenchyma induces local and subsequently systemic inflammation
      that results in a complex disease called mastitis. Globally Staphylococcus aureus
      is the single largest mastitis pathogen and the infection can ultimately result
      in either subclinical or chronic and sometimes lifelong infection. RESULTS: In
      the present report we have addressed the differential inflammatory response in
      mice mammary tissue during intramammary infection and the altered epigenetic
      context induced by two closely related strains of S. aureus, isolated from field
      samples. Immunohistochemical and immunoblotting analysis showed strain specific
      hyperacetylation at histone H3K9 and H3K14 residues. Global gene expression
      analysis in S. aureus infected mice mammary tissue revealed a selective set of
      upregulated genes that significantly correlated with the promoter specific,
      histone H3K14 acetylation. Furthermore, we have identified several differentially
      expressed known miRNAs and 3 novel miRNAs in S. aureus infected mice mammary
      tissue by small RNA sequencing. By employing these gene expression data, an
      attempt has been made to delineate the gene regulatory networks in the strain
      specific inflammatory response. Apparently, one of the isolates of S. aureus
      activated the NF-kappaB signaling leading to drastic inflammatory response and
      induction of immune surveillance, which could possibly lead to rapid clearance of
      the pathogen. The other strain repressed most of the inflammatory response, which
      might help in its sustenance in the host tissue. CONCLUSION: Taken together, our
      studies shed substantial lights to understand the mechanisms of strain specific
      differential inflammatory response to S. aureus infection during mastitis. In a
      broader perspective this study also paves the way to understand how certain
      bacteria can evade the immune surveillance and cause sustained infection while
      others are rapidly cleared from the host body.

PMID- 25075226
TI  - Application of Multiphoton Microscopy in Dermatological Studies: a Mini-Review.
AB  - This review summarizes the historical and more recent developments of multiphoton
      microscopy, as applied to dermatology. Multiphoton microscopy offers several
      advantages over competing microscopy techniques: there is an inherent axial
      sectioning, penetration depths that compete well with confocal microscopy on
      account of the use of near-infrared light, and many two-photon contrast
      mechanisms, such as second-harmonic generation, have no analogue in one-photon
      microscopy. While the penetration depths of photons into tissue are typically
      limited on the order of hundreds of microns, this is of less concern in
      dermatology, as the skin is thin and readily accessible. As a result, multiphoton
      microscopy in dermatology has generated a great deal of interest, much of which
      is summarized here. The review covers the interaction of light and tissue, as
      well as the various considerations that must be made when designing an
      instrument. The state of multiphoton microscopy in imaging skin cancer and
      various other diseases is also discussed, along with the investigation of aging
      and regeneration phenomena, and finally, the use of multiphoton microscopy to
      analyze the transdermal transport of drugs, cosmetics and other agents is
      summarized. The review concludes with a look at potential future research
      directions, especially those that are necessary to push these techniques into
      widespread clinical acceptance.

PMID- 25075228
TI  - Flammer syndrome.
AB  - The new term Flammer syndrome describes a phenotype characterized by the presence
      of primary vascular dysregulation together with a cluster of symptoms and signs
      that may occur in healthy people as well as people with disease. Typically, the
      blood vessels of the subjects with Flammer syndrome react differently to a number
      of stimuli, such as cold and physical or emotional stress. Nearly all organs,
      particularly the eye, can be involved. Although the syndrome has some advantages,
      such as protection against the development of atherosclerosis, Flammer syndrome
      also contributes to certain diseases, such as normal tension glaucoma. The
      syndrome occurs more often in women than in men, in slender people than in obese
      subjects, in people with indoor rather than outdoor jobs, and in academics than
      in blue collar workers. Affected subjects tend to have cold extremities, low
      blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced
      feeling of thirst, altered drug sensitivity, and increased general sensitivity,
      including pain sensitivity. The plasma level of endothelin-1 is slightly
      increased, and the gene expression in lymphocytes is changed. In the eye, the
      retinal vessels are stiffer and their spatial variability larger; the
      autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer
      syndrome have an increased frequency of the following: optic disc hemorrhages,
      activated retinal astrocytes, elevated retinal venous pressure, optic nerve
      compartmentalization, fluctuating diffuse visual field defects, and elevated
      oxidative stress. Further research should lead to a more concise definition, a
      precise diagnosis, and tools for recognizing people at risk. This may ultimately
      lead to more efficient and more personalized treatment. 

PMID- 25075229
TI  - ePatients on YouTube: analysis of four experiences from the patients'
      perspective.
AB  - BACKGROUND: Many patients share their personal experiences and opinions using
      online video platforms. These videos are watched by millions of health consumers
      and health care professionals. Although it has become a popular phenomenon,
      little is known about patients who share videos online and why they do so.
      OBJECTIVE: We aimed to explore the motivations and challenges faced by patients
      who share videos about their health and experiences on YouTube. As part of a
      conference discussion, we asked several patients actively engaged on YouTube to
      make a video explaining their motivations. This paper discusses these videos.
      METHODS: In this qualitative study, we performed an analysis of the videos
      created by 4 patients about their self-reported motivations and challenges they
      face as YouTube users. First, two judges compared the transcriptions and decided
      the exact wording when confusing content was found. Second, two judges
      categorized the content of the videos to identify the major themes. RESULTS: four
      main categories emerged: (1) the origin or cause for making the first video, (2)
      the objectives that they achieve by continuing to make videos, (3) the perception
      of community, and (4) the negative consequences of the experience. CONCLUSIONS:
      The main reason for making videos was to bridge the gap between traditional
      health information about their diseases and everyday life. The first consequence
      of sharing their life on YouTube was a loss of privacy. However, they also
      experienced the positive effects of expressing their feelings, being part of a
      large community of peers, and helping others to deal with a chronic condition.

PMID- 25075230
TI  - Physicians' motives for professional internet use and differences in attitudes
      toward the internet-informed patient, physician-patient communication, and
      prescribing behavior.
AB  - BACKGROUND: Physicians have differing motives for using the Internet and Internet
      related services in their professional work. These motives may affect their
      evaluation of patients who bring with them health-related information from the
      Internet. Differing motives may also affect physician-patient communication and
      subsequent prescribing behavior. OBJECTIVES: to segment physicians into types
      based on their motives for using the internet in connection with professional
      activities and to analyze how those segments differ in their attitudes in three
      areas: toward patients who bring along Internet-sourced information; in their own
      subsequent prescribing behavior; and in their attitudes toward using the Internet
      to communicate with patients in future. METHODS: We surveyed 287 German
      physicians online from three medical fields. To assess physicians' motives for
      using the Internet for their professional activities, we asked them to rate their
      level of agreement with statements on a 7-point scale. Motive statements were
      reduced to motive dimensions using principal component analysis, and 2-step
      cluster analysis based on motive dimensions identified different segments of
      physicians. Several statements assessed agreement or disagreement on a 7-point
      scale physicians' attitudes toward patients' bringing Internet information to the
      consultation and their own subsequent prescribing behavior. Further, we asked
      physicians to indicate on a 7-point scale their valuation of the Internet for
      physician-patient communication in the future. Data were then subjected to
      variance and contingency analyses. RESULTS: we identified three motive dimensions
      for internet use: (1) being on the cutting edge and for self-expression (Cronbach
      alpha = .88), (2) efficiency and effectiveness (alpha = .79), and (3) diversity
      and convenience (alpha = .71). These three factors accounted for 71.4% of the
      variance. Based on physicians' motives for using the Internet, four types of
      physician Internet user were identified: (1) the Internet Advocate (2),
      Efficiency-Oriented, (3) Internet Critic, and (4) Driven Self-expressionist.
      Groups differed significantly concerning (1) their attitude toward informed
      patients in general (F 1234 = 9.215, P < .001), (2) perceived improvement in the
      physician-patient relationship Internet information brings (F 1234 = 5.386, P <
      .001), (3) perceived accuracy of information the patient brings (F 1234 = 3.658,
      P = .01), and (4) perceived amount of time needed to devote to an Internet
      informed patient (F 1234 = 3.356, P = .02). Physician segments did not differ
      significantly in reported prescribing behavior (F 1234 = 1.910, P = .13).
      However, attitudes toward using the Internet to communicate with patients in
      future differed significantly (F 1234 = 23.242, P < .001). CONCLUSIONS: Based on
      self-reporting by German physicians of their motives for professional Internet
      use, we identified four types of Internet users who differ significantly in their
      attitude toward patients who bring along Internet information and their attitudes
      toward using the Internet to communicate with patients in future.

PMID- 25075232
TI  - InSpire to Promote Lung Assessment in Youth: Evolving the Self-Management
      Paradigms of Young People With Asthma.
AB  - BACKGROUND: Asthma is the most common chronic disease in childhood,
      disproportionately affecting urban, minority, and disadvantaged children.
      Individualized care plans supported by daily lung-function monitoring can reduce
      morbidity and mortality. However, despite 20 years of interventions to increase
      adherence, only 50% of US youth accurately follow their care plans, which leads
      to millions of preventable hospitalizations, emergency room visits, and sick days
      every year. We present a feasibility study of a novel, user-centered approach to
      increasing young people's lung-function monitoring and asthma self-care.
      Promoting Lung Assessment in Youth (PLAY) helps young people become active
      managers of their asthma through the Web 2.0 principles of participation,
      cocreation, and information sharing. Specifically, PLAY combines an inexpensive,
      portable spirometer with the motivational power and convenience of mobile phones
      and virtual-community gaming. OBJECTIVE: The objective of this study was to
      develop and pilot test InSpire, a fully functional interface between a handheld
      spirometer and an interactive game and individualized asthma-care instant
      messaging system housed on a mobile phone. METHODS: InSpire is an application for
      mobile smartphones that creates a compelling world in which youth collaborate
      with their physicians on managing their asthma. Drawing from design-theory on
      global timer mechanics and role playing, we incentivized completing spirometry
      maneuvers by making them an engaging part of a game young people would want to
      play. The data can be sent wirelessly to health specialists and return care
      recommendations to patients in real-time. By making it portable and similar to
      applications normally desired by the target demographic, InSpire is able to
      seamlessly incorporate asthma management into their lifestyle. RESULTS: We
      describe the development process of building and testing the InSpire prototype.
      To our knowledge, the prototype is a first-of-its kind mobile one-stop shop for
      asthma management. Feasibility testing in children aged 7 to 14 with asthma
      assessed likability of the graphical user interface as well as young people's
      interest in our incentivizing system. Nearly 100% of children surveyed said they
      would play games like those in PLAY if they involved breathing into a spirometer.
      Two-thirds said they would prefer PLAY over the spirometer alone, whereas 1/3
      would prefer having both. No children said they would prefer the spirometer over
      PLAY. CONCLUSIONS: Previous efforts at home-monitoring of asthma in children have
      experienced rapid decline in adherence. An inexpensive monitoring technology
      combined with the computation, interactive communication, and display ability of
      a mobile phone is a promising approach to sustainable adherence to lung-function
      monitoring and care plans. An exciting game that redefines the way youth conduct
      health management by inviting them to collaborate in their health better can be
      an incentive and a catalyst for more far-reaching goals.

PMID- 25075231
TI  - Web-based interventions for behavior change and self-management: potential,
      pitfalls, and progress.
AB  - The potential advantages of using the Internet to deliver self-care and behavior
      change programs are well recognized. An aging population combined with the
      increasing prevalence of long-term conditions and more effective medical
      interventions place financial strain on all health care systems. Web-based
      interventions have the potential to combine the tailored approach of face-to-face
      interventions with the scalability of public health interventions that have low
      marginal costs per additional user. From a patient perspective, Web-based
      interventions can be highly attractive because they are convenient, easily
      accessible, and can maintain anonymity/privacy. Recognition of this potential has
      led to research in developing and evaluating Web-based interventions for self
      management of long-term conditions and behavior change. Numerous systematic
      reviews have confirmed the effectiveness of some Web-based interventions, but a
      number of unanswered questions still remain. This paper reviews the progress made
      in developing and evaluating Web-based interventions and considers three
      challenging areas: equity, effectiveness, and implementation. The impact of Web
      based interventions on health inequalities remains unclear. Although some have
      argued that such interventions can increase access to underserved communities,
      there is evidence to suggest that reliance on Web-based interventions may
      exacerbate health inequalities by excluding those on the "wrong" side of the
      digital divide. Although most systematic reviews have found a positive effect on
      outcomes of interest, effect sizes tend to be small and not all interventions are
      successful. Further work is needed to determine why some interventions work and
      others do not. This includes considering the "active ingredients" or mechanism of
      action of these complex interventions and the context in which they are used. Are
      there certain demographic, psychological, or clinical factors that promote or
      inhibit success? Are some behaviors or some clinical problems more amenable to
      change by computer-based interventions? Equally problematic is the issue of
      implementation and integration of such programs into routine clinical practice.
      Many eHealth projects end when the research is concluded and fail to become part
      of mainstream clinical care. One way of addressing these challenges is to apply
      the Medical Research Council framework for developing, evaluating, and
      implementing complex interventions. This includes having a strong theoretical
      foundation, developing a proposed mechanism or pathway of action, ensuring that
      the evaluation adequately reflects this proposed pathway, and considering
      implementation from the beginning of the development process. 

PMID- 25075234
TI  - Clinicians' assessment of mobile monitoring: a comparative study in Japan and
      Spain.
AB  - BACKGROUND: The gradual but steady shift toward telemedicine during the past
      decades is a clear response to important health problems that most industrialized
      countries have been facing. The growing elderly population and changing dietary
      habits have led to an increase in people with chronic diseases and overall health
      care expenditures. As more consumers use their mobile device as their preferred
      information and communication technology (ICT) device, mobile health monitoring
      has been receiving increasing attention in recent years. OBJECTIVE: This study
      examines clinicians' perception of factors determining mobile health monitoring
      acceptance in Japan and Spain. The study proposes a causal model consisting of
      innovation seeking, new ICT attributes (perceived value, time-place flexibility,
      and compatibility), and usage intention. In addition, cross-country differences
      are posited for the hypothesized relationships among the proposed constructs.
      METHODS: A questionnaire survey was performed to test our research model and
      hypotheses. The sample consisted of clinicians from various medical specialties.
      In total, 471 and 497 usable responses were obtained in Japan and Spain,
      respectively. RESULTS: In both countries, the collected data fit the model well
      with all the hypothesized paths among the constructs being supported.
      Furthermore, the moderating effects of psychic distance were observed in most of
      the paths. CONCLUSIONS: Our study demonstrates the importance of new ICT
      attributes, namely perceived value, time-place flexibility, and compatibility, in
      the clinicians' adoption of mobile health monitoring. In particular, our results
      clearly indicated that perceived medical value and ubiquitous nature of the tool
      are the two main benefits clinicians are likely to perceive (and appreciate) in
      both countries. This tendency will be stronger for those with a greater
      propensity to seek innovation in ICT. In terms of cross-country comparison, the
      strength of the path from innovation seeking to perceived value was greater in
      Japan than in Spain. Since the number of clinicians per 10,000 residents is
      substantially fewer in Japan compared with Spain, clinicians with a greater
      propensity to seek innovation in ICT may have perceived greater value in using
      mobile health monitoring to improve remote patient care.

PMID- 25075233
TI  - eHealth Technology Competencies for Health Professionals Working in Home Care to
      Support Older Adults to Age in Place: Outcomes of a Two-Day Collaborative
      Workshop.
AB  - BACKGROUND: The demand for care is increasing, whereas in the near future the
      number of people working in professional care will not match with the demand for
      care. eHealth technology can help to meet the growing demand for care. Despite
      the apparent positive effects of eHealth technology, there are still barriers to
      technology adoption related to the absence of a composite set of knowledge and
      skills among health care professionals regarding the use of eHealth technology.
      OBJECTIVE: The objective of this paper is to discuss the competencies required by
      health care professionals working in home care, with eHealth technologies such as
      remote telecare and ambient assisted living (AAL), mobile health, and fall
      detection systems. METHODS: A two-day collaborative workshop was undertaken with
      academics across multiple disciplines with experience in working on funded
      research regarding the application and development of technologies to support
      older people. RESULTS: The findings revealed that health care professionals
      working in home care require a subset of composite skills as well as technology
      specific competencies to develop the necessary aptitude in eHealth care. This
      paper argues that eHealth care technology skills must be instilled in health care
      professionals to ensure that technologies become integral components of future
      care delivery, especially to support older adults to age in place. Educating
      health care professionals with the necessary skill training in eHealth care will
      improve service delivery and optimise the eHealth care potential to reduce costs
      by improving efficiency. Moreover, embedding eHealth care competencies within
      training and education for health care professionals ensures that the benefits of
      new technologies are realized by casting them in the context of the larger system
      of care. These care improvements will potentially support the independent living
      of older persons at home. CONCLUSIONS: This paper describes the health care
      professionals' competencies and requirements needed for the use of eHealth
      technologies to support elderly adults to age in place. In addition, this paper
      underscores the need for further discussion of the changing role of health care
      professionals working in home care within the context of emerging eHealth care
      technologies. The findings are of value to local and central government, health
      care professionals, service delivery organizations, and commissioners of care to
      use this paper as a framework to conduct and develop competencies for health care
      professionals working with eHealth technologies.

PMID- 25075235
TI  - Participatory Design With Seniors: Design of Future Services and Iterative
      Refinements of Interactive eHealth Services for Old Citizens.
AB  - BACKGROUND: There is an increasing social isolation among the elderly today. This
      will be an even larger issue in the future with growing numbers of elderly and
      less resources, for example, in terms of economy and staff. Loneliness and social
      isolation can, however, be addressed in several ways using different interactive
      eHealth services. OBJECTIVE: This case study investigated novel eHealth services
      for the elderly, and their usage of a social interactive device designed
      especially for them. METHODS: In this work, we used an innovative mobile
      communication device connected to the television (TV), which worked as a remotely
      controlled large interactive screen. The device was tested by 8 volunteers who
      visited a senior center. They were between 65 and 80 years of age and lived in
      their own homes. Throughout the 1.5 year-long project, 7 design workshops were
      held with the seniors and the staff at the center. During these workshops,
      demands and preferences regarding existing and new services were gathered. At the
      end of the project the participants' experience of the device and of the services
      was elaborated in 3 workshops to get ideas for improved or new meaningful
      services. During the data analyses and development process, what seniors thought
      would be useful in relation to what was feasible was prioritized by the
      development company. RESULTS: Regarding daily usage, the seniors reported that
      they mainly used the service for receiving information from the senior center and
      for communication with other participants in the group or with younger relatives.
      They also read information about events at the senior center and they liked to
      perform a weekly sent out workout exercise. Further, they played games such as
      Memory and Sudoku using the device. The service development focused on three
      categories of services: cognitive activities, social activities, and physical
      activities. A cognitive activity service that would be meaningful to develop was
      a game for practicing working memory. In the social activities category, the
      seniors wanted different quizzes and multi-player games. For physical activities,
      the seniors desired more workout exercises and suggestions for guided walking
      routes. A new category, "information and news", was suggested since they lacked
      services like senior-customized global and local news. CONCLUSIONS: This study
      showed the importance of input from a group of seniors when designing new
      services for elderly citizens. Besides input to interactive eHealth service
      development for seniors, this study showed the importance of a social context
      around such work. The seniors were very engaged throughout the project and
      workshops were frequently visited and the seniors became friends. The high amount
      of input from the seniors could be explained in terms of social inclusion; they
      belonged to a group and each member was considered important for the work. The
      friendly workshop atmosphere facilitated new ideas and redesign of the services.

PMID- 25075236
TI  - Embedding a learning management system into an undergraduate medical informatics
      course in Saudi Arabia: lessons learned.
AB  - BACKGROUND: Public universities in Saudi Arabia today are making substantial
      investments in e-learning as part of their educational system, especially in the
      implementation of learning management systems (LMS). To our knowledge, this is
      the first study conducted in Saudi Arabia exploring medical students' experience
      with an LMS, particularly as part of a medical informatics course. OBJECTIVE:
      This study investigates students' use of various features of the LMS embedded in
      a recently implemented medical informatics course. METHODS: A mixed methodology
      approach was employed. Survey questionnaires were distributed to all third year
      medical informatics students at the end of the course. In addition, two focus
      group sessions were conducted with twelve students. A thematic analysis of the
      focus group was performed. RESULTS: A total of 265 third year medical student
      surveys (167/265, 63% male and 98/265, 37% female) were completed and analyzed.
      Overall, 50.6% (134/265) of the students agreed that the course was well planned
      and up-to-date, had clearly stated objectives and clear evaluation methods,
      appropriate course assignment, and that the LMS offered easy navigation. Most of
      the students rated the course as good/fair overall. In general, females were
      10.4% more likely to prefer the LMS, as revealed by higher odd ratios (odds ratio
      [OR] 1.104, 95% CI 0.86-1.42) compared to males. Survey results showed that
      students' use of LMS tools increased after taking the course compared to before
      taking the course. The full model containing all items were statistically
      significant (chi(2) 25=69.52, P<.001, n=243), indicating that the model was able
      to distinguish between students who had positive attitudes towards LMS and those
      who did not. The focus group, however, revealed that the students used social
      networking for general use rather than learning purposes, but they were using
      other Internet resources and mobile devices for learning. Male students showed a
      higher preference for using technology in general to enhance learning activities.
      Overall, medical student attitudes towards the LMS were generally positive.
      Students also wanted a reminder and notification tool to help them stay updated
      with course events. Interestingly, a subset of students had been running a
      parallel LMS of their own that has features worth exploring and could be
      integrated with an official LMS in the future. CONCLUSIONS: To our knowledge,
      this was the first time that an LMS was used in a medical informatics course.
      Students showed interest in adapting various LMS tools to enhance their learning
      and gained more knowledge through familiarity with the tool. Researching an
      official LMS also revealed the existence of a parallel student-created LMS. This
      could allow teacher-led and student-led platforms to be integrated in the future
      for an enhanced student-centered experience.

PMID- 25075238
TI  - Developing a framework to generate evidence of health outcomes from social media
      use in chronic disease management.
AB  - BACKGROUND: While there is an abundance of evidence-based practice (EBP)
      recommendations guiding management of various chronic diseases, evidence
      suggesting best practice for using social media to improve health outcomes is
      inadequate. The variety of social media platforms, multiple potential uses,
      inconsistent definitions, and paucity of rigorous studies, make it difficult to
      measure health outcomes reliably in chronic disease management. Most published
      investigations report on an earlier generation of online tools, which are not as
      user-centered, participatory, engaging, or collaborative, and thus may work
      differently for health self-management. OBJECTIVE: The challenge to establish a
      sound evidence base for social media use in chronic disease starts with the need
      to define criteria and methods to generate and evaluate evidence. The authors'
      key objective is to develop a framework for research and practice that addresses
      this challenge. METHODS: This paper forms part of a larger research project that
      presents a conceptual framework of how evidence of health outcomes can be
      generated from social media use, allowing social media to be utilized in chronic
      disease management more effectively. Using mixed methods incorporating a
      qualitative literature review, a survey and a pilot intervention, the research
      closely examines the therapeutic affordances of social media, people with chronic
      pain (PWCP) as a subset of chronic disease management, valid outcome measurement
      of patient-reported (health) outcomes (PRO), the individual needs of people
      living with chronic disease, and finally translation of the combined results to
      improve evidence-based decision making about social media use in this context.
      RESULTS: Extensive review highlights various affordances of social media that may
      prove valuable to understanding social media's effect on individual health
      outcomes. However, without standardized PRO instruments, we are unable to
      definitively investigate these effects. The proposed framework that we offer
      outlines how therapeutic affordances of social media coupled with valid and
      reliable PRO measurement may be used to generate evidence of improvements in
      health outcomes, as well as guide evidence-based decision making in the future
      about social media use as part of chronic disease self-management. CONCLUSIONS:
      The results will (1) inform a framework for conducting research into health
      outcomes from social media use in chronic disease, as well as support translating
      the findings into evidence of improved health outcomes, and (2) inform a set of
      recommendations for evidence-based decision making about social media use as part
      of chronic disease self-management. These outcomes will fill a gap in the
      knowledge and resources available to individuals managing a chronic disease,
      their clinicians and other researchers in chronic disease and the field of
      medicine 2.0.

PMID- 25075239
TI  - Health care social media: expectations of users in a developing country.
AB  - BACKGROUND: Affordability, acceptability, accommodation, availability, and
      accessibility are the five most important dimensions of access to health
      services. Seventy two percent of the Indian population lives in semi-urban and
      rural areas. The strong mismatched ratio of hospitals to patients, rising costs
      of health care, rapidly changing demographics, increasing population, and
      heightened demands in pricing for technological health care usage in emerging
      economies necessitate a unique health delivery solution model using social media.
      A greater disease burden lies in the health care delivery in developing country
      like India. This is due to the lack of health care infrastructure in the majority
      of semi-urban and rural regions. New techniques need to be introduced in these
      regions to overcome these issues. In the present scenario, people use social
      media from business, automobiles, arts, book marking, cooking, entertainment, and
      general networking. Developed and advanced countries like the United States have
      developed their communication system for many years now. They have already
      established social media in a number of domains including health care. Similar
      practice incidences can be used to provide a new dimension to health care in the
      semi-urban regions of India. OBJECTIVE: This paper describes an extended study of
      a previous empirical study on the expectations of social media users for health
      care. The paper discusses what the users of social media expect from a health
      care social media site. METHODS: Multiple regression analysis was used to
      determine the significance of the affect of four factors (privacy, immediacy,
      usability, and communication) on the usage of health care social media. Privacy,
      immediacy, usability, and communication were the independent variables and health
      care social media was the dependant variable. RESULTS: There were 103 respondents
      who used the online questionnaire tool to generate their responses. The results
      from the multiple regression analysis using SPSS 20 showed that the model is
      acceptable, with P=.011, which is statistically significant on a P<.05 level. The
      observed F value (2.082) in ANOVA was less than the given value in the F table
      (2.61), which allowed us to accept the hypothesis that the independent variables
      influence the dependant variable. The users of social media in India expect that
      they can best utilize social media through emergency service information. They
      want to be able to learn the operations of the social media site quickly and
      expect to know about health camps and insurance collaborations. However, people
      like to become friends with people with similar interests based on their
      interests identified. CONCLUSIONS: Health care social media requires intelligent
      implementation in developing economies. It needs to cater to the expectations of
      the users. The people in India, especially those in urban and semi-urban regions,
      are very interested in accepting the system.

PMID- 25075237
TI  - How Twitter Is Studied in the Medical Professions: A Classification of Twitter
      Papers Indexed in PubMed.
AB  - BACKGROUND: Since their inception, Twitter and related microblogging systems have
      provided a rich source of information for researchers and have attracted interest
      in their affordances and use. Since 2009 PubMed has included 123 journal articles
      on medicine and Twitter, but no overview exists as to how the field uses Twitter
      in research. OBJECTIVE: This paper aims to identify published work relating to
      Twitter within the fields indexed by PubMed, and then to classify it. This
      classification will provide a framework in which future researchers will be able
      to position their work, and to provide an understanding of the current reach of
      research using Twitter in medical disciplines. METHODS: Papers on Twitter and
      related topics were identified and reviewed. The papers were then qualitatively
      classified based on the paper's title and abstract to determine their focus. The
      work that was Twitter focused was studied in detail to determine what data, if
      any, it was based on, and from this a categorization of the data set size used in
      the studies was developed. Using open coded content analysis additional important
      categories were also identified, relating to the primary methodology, domain, and
      aspect. RESULTS: As of 2012, PubMed comprises more than 21 million citations from
      biomedical literature, and from these a corpus of 134 potentially Twitter related
      papers were identified, eleven of which were subsequently found not to be
      relevant. There were no papers prior to 2009 relating to microblogging, a term
      first used in 2006. Of the remaining 123 papers which mentioned Twitter, thirty
      were focused on Twitter (the others referring to it tangentially). The early
      Twitter focused papers introduced the topic and highlighted the potential, not
      carrying out any form of data analysis. The majority of published papers used
      analytic techniques to sort through thousands, if not millions, of individual
      tweets, often depending on automated tools to do so. Our analysis demonstrates
      that researchers are starting to use knowledge discovery methods and data mining
      techniques to understand vast quantities of tweets: the study of Twitter is
      becoming quantitative research. CONCLUSIONS: This work is to the best of our
      knowledge the first overview study of medical related research based on Twitter
      and related microblogging. We have used 5 dimensions to categorize published
      medical related research on Twitter. This classification provides a framework
      within which researchers studying development and use of Twitter within medical
      related research, and those undertaking comparative studies of research, relating
      to Twitter in the area of medicine and beyond, can position and ground their
      work.

PMID- 25075240
TI  - The ligurian human immunodeficiency virus clinical network: a web tool to manage
      patients with human immunodeficiency virus in primary care and multicenter
      clinical trials.
AB  - BACKGROUND: In recent years, Highly-Active Anti-Retroviral Therapies (HAARTs)
      have modified the Human Immunodeficiency Virus (HIV) life-cycle and the disease
      is now considered chronic. Consequently, a longitudinal and complex follow-up is
      now required for HIV positive patients during their lifetime. Moreover, patients
      often encounter various complications due to comorbidities, related to the
      immunodeficiency state and HAARTs' side effects. Thus, HIV positive patients are
      involved in multicenter clinical trials (MCTs) to improve treatments and discover
      a preventive vaccine. Therefore, physicians require proper instruments to access
      comprehensive patient data for managing patients during follow-ups, and tools for
      data collection and analysis in MCTs. OBJECTIVE: The Ligurian HIV Clinical
      Network aims to provide physicians with a Web-tool to administrate HIV positive
      patients' data within primary-care and to reuse the collected clinical
      information to perform MCTs in Northern Italy. METHODS: The key aspect of the
      system is a relational database which allows the storage of various types of
      clinical information (eg, related to HIV, cardiovascular, or hepatic diseases) in
      multiple formats. The modular design of the database permits a rapid insertion of
      new parameters without requiring any changes in the database structure.
      Furthermore, codes from biomedical ontologies controlled vocabularies ("Logical
      Observation Identifier Names and Codes", and "International Classification of
      Diseases 9") and ontologies ("Systematized Nomenclature of Medicine Clinical
      Terms"), units and normality ranges used by all partners participating in the
      project were collected to achieve a complete semantic interoperability.
      Accordingly, data can be automatically normalized through the z score formula and
      physicians can extract and correctly compare information with external
      statistical tools. Moreover, to respect patients' privacy and legal issues, a
      local identifier, determined through an HASH cryptography algorithm, is assigned
      to each patient during the registration process. The database is managed by a
      user-friendly Web-platform which allows quick access to information during
      medical examinations and the reusing of the collected data for present and future
      MCTs. Furthermore, a bidirectional middleware was created in order to
      import/export information through HL7 messaging. Hence, data can be manually
      entered by physicians or automatically collected within HL7-compliant Hospital
      Information systems. RESULTS: Presently, the direct storage of patients'
      information from the San Paolo Hospital (Savona, Italy), and San Martino and
      Galliera hospitals in Genoa is in a test phase. Currently, 8 centers of
      Infectious Diseases (located in Liguria and Piedmont) are participating in the
      project and almost 400 HIV positive patients have been recorded in the system.
      Patient data has been used for primary care and research purposes. Currently,
      there are 4 on-going MCTs and preliminary results have already been presented at
      International HIV congresses. CONCLUSIONS: The Web-platform allows effective
      management, sharing and reuse of information within primary care and clinical
      research. In the future it is planned to share the clinical information from this
      network with other HL7-compliant workgroups and to extend the platform to other
      infective diseases (eg, hepatitis).

PMID- 25075241
TI  - Acceptance of e-learning devices by dental students.
AB  - BACKGROUND: E-Learning programs and their corresponding devices are increasingly
      employed to educate dental students during their clinical training. OBJECTIVE:
      Recent progress made in the development of e-learning software as well as in
      hardware (computers, tablet PCs, smartphones) caused us to more closely
      investigate into the habits of dental students in dealing with these learning
      techniques. METHODS: Dental students during their clinical training attended a
      survey compiled in cooperation with biostatisticians. The questionnaire probands
      were asked to complete based on previous surveys of similar subjects, allowing
      single as well as multiple answers. The data, which were obtained with respect to
      the learning devices students commonly employ, were compared with their internet
      learning activities. RESULTS: The e-learning devices utilized are of
      heterogeneous brands. Each student has access to at least one hardware type
      suitable for e-learning. All students held mobile devices, about 90 percent
      employed laptops, and about 60 percent possess smartphones. Unexceptional all
      participants of the survey acknowledged an unlimited internet access. In
      contrast, only 16 percent of students utilized tablet PCs. A detailed analysis of
      the survey outcome reveals that an increasing use of mobile devices (tablet PC,
      smartphone) facilitates internet learning activities while at the same time
      utilization of computers (desktop, laptop) declines. CONCLUSIONS: Dental students
      overwhelmingly accept e-learning during their clinical training. Students report
      outstanding preconditions to conduct e-learning as both their access to hardware
      and to the internet is excellent. Less satisfying is the outcome of our survey
      regarding the utilization of e-learning programs. Depending of the hardware
      employed only one-third to barely one-half of students comprise learning
      programs.

PMID- 25075242
TI  - Live long and prosper: potentials of low-cost consumer devices for the prevention
      of cardiovascular diseases.
AB  - BACKGROUND: Cardiovascular diseases (CVD) are one of the major causes of death
      worldwide. Personal behavior such as physical activity considerably influences
      the risk of incurring a CVD. In the last years numerous products such as
      pedometers have become available on the mass market that allow monitoring
      relevant behaviors and vital parameters. These devices are sufficiently precise,
      affordable, and easy to use. While today they are mostly lifestyle oriented they
      also have considerable potential for health and prevention. OBJECTIVE: Our goal
      is to investigate how recent low-cost devices can be used in real-life settings
      for the prevention of CVD, and whether using these devices has an advantage over
      subjective self-assessment. We also examine whether it is feasible to use
      multiple of such devices in parallel. METHODS: We observe whether and how persons
      are willing and able to use multiple devices in their daily lives. We compare the
      devices' measurements with subjective self-assessment. We make use of existing
      low-cost consumer devices to monitor a user's behavior. By mapping the devices'
      features with pre-defined prevention goals we ensure that the system collects
      meaningful data that can be used to monitor the individual's behavior. We
      conducted a user study with 10 healthy adults to measure usability and to
      identify problems with sensor use in real life. The participants used the
      devices' original portals to monitor their behavior. The subjects (age range 35
      75) used an off-the-shelf pedometer and a sports watch for 4 weeks. RESULTS: The
      participants responded in principle positively to the use of the devices.
      Analyzing the sensor data, we found that the users had some difficulties in
      operating the devices. We also found that the participants' self-assessment of
      their health behavior was too optimistic compared to the monitored data. They
      rated the usability of the overall system with 71 of up to 100 points in the
      "System Usability Scale". CONCLUSIONS: Our study indicates that today's devices
      are suitable for a long term monitoring of health for the prevention of CVD.
      Using the devices provides more precise data than a subjective self-assessment.
      However usability and acceptance of the systems are still major topics.

PMID- 25075243
TI  - Validity and Reliability of the eHealth Analysis and Steering Instrument.
AB  - BACKGROUND: eHealth services can contribute to individuals' self-management, that
      is, performing lifestyle-related activities and decision making, to maintain a
      good health, or to mitigate the effect of an (chronic) illness on their health.
      But how effective are these services? Conducting a randomized controlled trial
      (RCT) is the golden standard to answer such a question, but takes extensive time
      and effort. The eHealth Analysis and Steering Instrument (eASI) offers a quick,
      but not dirty alternative. The eASI surveys how eHealth services score on 3
      dimensions (ie, utility, usability, and content) and 12 underlying categories
      (ie, insight in health condition, self-management decision making, performance of
      self-management, involving the social environment, interaction, personalization,
      persuasion, description of health issue, factors of influence, goal of eHealth
      service, implementation, and evidence). However, there are no data on its
      validity and reliability. OBJECTIVE: The objective of our study was to assess the
      construct and predictive validity and interrater reliability of the eASI.
      METHODS: We found 16 eHealth services supporting self-management published in the
      literature, whose effectiveness was evaluated in an RCT and the service itself
      was available for rating. Participants (N=16) rated these services with the eASI.
      We analyzed the correlation of eASI items with the underlying three dimensions
      (construct validity), the correlation between the eASI score and the eHealth
      services' effect size observed in the RCT (predictive validity), and the
      interrater agreement. RESULTS: Three items did not fit with the other items and
      dimensions and were removed from the eASI; 4 items were replaced from the utility
      to the content dimension. The interrater reliabilities of the dimensions and the
      total score were moderate (total, kappa=.53, and content, kappa=.55) and
      substantial (utility, kappa=.69, and usability, kappa=.63). The adjusted eASI
      explained variance in the eHealth services' effect sizes (R(2) =.31, P<.001), as
      did the dimensions utility (R(2) =.49, P<.001) and usability (R(2) =.18, P=.021).
      Usability explained variance in the effect size on health outcomes (R(2) =.13,
      P=.028). CONCLUSIONS: After removing 3 items and replacing 4 items to another
      dimension, the eASI (3 dimensions, 11 categories, and 32 items) has a good
      construct validity and predictive validity. The eASI scales are moderately to
      highly reliable. Accordingly, the eASI can predict how effective an eHealth
      service is in regard to supporting self-management. Due to a small pool of
      available eHealth services, it is advised to reevaluate the eASI in the future
      with more services.

PMID- 25075245
TI  - Analysis of twitter users' sharing of official new york storm response messages.
AB  - BACKGROUND: Twitter is a social network where users read, send, and share
      snippets of text ("tweets"). Tweets can be disseminated through multiple means;
      on desktop computers, laptops, and mobile devices, over ethernet, Wi-Fi or
      cellular networks. This redundancy positions Twitter as a useful tool for
      disseminating information to the public during emergencies or disasters. Previous
      research on dissemination of information using Twitter has mostly investigated
      the characteristics of tweets that are most effective in raising consumer
      awareness about a new product or event. In particular, they describe
      characteristics that increase the chance the messages will be shared
      ("retweeted") by users. In comparison, little has been published on how
      information from municipal or state government agencies spreads on Twitter during
      emergency situations. Retweeting these messages is a way to enhance public
      awareness of potentially important instructions from public officials in a
      disaster. OBJECTIVE: The aim of this study is to (1) describe the tweets of
      select New York State and New York City agencies by public officials surrounding
      two notable recent winter storms that required a large-scale emergency response,
      and (2) identify the characteristics of the tweets of public officials that were
      most disseminated (retweeted). METHODS: For one week surrounding Superstorm Sandy
      (October 2012) and the winter blizzard Nemo (February 2013), we collected (1)
      tweets from the official accounts for six New York governmental agencies, and (2)
      all tweets containing the hashtags #sandy (or #nemo) and #nyc. From these data we
      calculated how many times a tweet was retweeted, controlling for differences in
      baseline activity in each account. We observed how many hashtags and links each
      tweet contained. We also calculated the lexical diversity of each tweet, a
      measure of the range of vocabulary used. RESULTS: During the Sandy storm, 3242
      shared (retweeted) messages from public officials were collected. The lexical
      diversity of official tweets was similar (2.25-2.49) and well below the average
      for non-official tweets mentioning #sandy and #nyc (3.82). Most official tweets
      were with substantial retweets including a link for further reading. Of the 448
      tweets analyzed from six official city and state Twitter accounts from the Nemo
      blizzard, 271 were related to the storm, and 174 had actionable information for
      the public. Actionable storm messages were retweeted approximately 24x per
      message, compared to 31x per message for general storm information. CONCLUSIONS:
      During two weather emergencies, New York public officials were able to convey
      storm-related information that was shared widely beyond existing follower bases,
      potentially improving situational awareness and disaster response. Official Sandy
      tweets, characterized by a lower lexical diversity score than other city- and
      Sandy-related tweets, were likely easier to understand, and often linked to
      further information and resources. Actionable information in the Nemo blizzard,
      such as specific instructions and cancellation notices, was not shared as often
      as more general warnings and "fun facts," suggesting agencies mix important
      instructions with more general news and trivia, as a way of reaching the broadest
      audience during a disaster.

PMID- 25075244
TI  - Development of a Questionnaire and Cross-Sectional Survey of Patient eHealth
      Readiness and eHealth Inequalities.
AB  - BACKGROUND: Many speak of the digital divide, but variation in the opportunity of
      patients to use the Internet for health (patient eHealth readiness) is not a
      binary difference, rather a distribution influenced by personal capability,
      provision of services, support, and cost. Digital divisions in health have been
      addressed by various initiatives, but there was no comprehensive validated
      measure to know if they are effective that could be used in randomized controlled
      trials (RCTs) covering both non-Internet-users and the range of Internet-users.
      OBJECTIVE: The aim of this study was to develop and validate a self-completed
      questionnaire and scoring system to assess patient eHealth readiness by examining
      the spread of scores and eHealth inequalities. The intended use of this
      questionnaire and scores is in RCTs of interventions aiming to improve patient
      eHealth readiness and reduce eHealth inequalities. METHODS: Based on four factors
      identified from the literature, a self-completed questionnaire, using a pragmatic
      combination of factual and attitude questions, was drafted and piloted in three
      stages. This was followed by a final population-based, cross-sectional household
      survey of 344 people used to refine the scoring system. RESULTS: the patient
      ehealth readiness questionnaire (perq) includes questions used to calculate four
      subscores: patients' perception of (1) provision, (2) their personal ability and
      confidence, (3) their interpersonal support, and (4) relative costs in using the
      Internet for health. These were combined into an overall PERQ score (0-9) which
      could be used in intervention studies. Reduction in standard deviation of the
      scores represents reduction in eHealth inequalities. CONCLUSIONS: PERQ appears
      acceptable for participants in British studies. The scores produced appear valid
      and will enable assessment of the effectiveness of interventions to improve
      patient eHealth readiness and reduce eHealth inequalities. Such methods need
      continued evolution and redevelopment for other environments. Full documentation
      and data have been published to allow others to develop the tool further.

PMID- 25075246
TI  - Transforming patient experience: health web science meets medicine 2.0.
AB  - Until recently, the Western biomedical paradigm has been effective in delivering
      health care, however this model is not positioned to tackle complex societal
      challenges or solve the current problems facing health care and delivery. The
      future of medicine requires a shift to a patient-centric model and in so doing
      the Internet has a significant role to play. The disciplines of Health Web
      Science and Medicine 2.0 are pivotal to this approach. This viewpoint paper
      argues that these disciplines, together with the field of design, can tackle
      these challenges. Drawing together ideas from design practice and research,
      complexity theory, and participatory action research we depict design as an
      approach that is fundamentally social and linked to concepts of person-centered
      care. We discuss the role of design, specifically co-design, in understanding the
      social, psychological, and behavioral dimensions of illness and the implications
      for the design of future care towards transforming the patient experience. This
      paper builds on the presentations and subsequent interdisciplinary dialogue that
      developed from the panel session "Transforming Patient Experience: Health Web
      Science Meets Web 2.0" at the 2013 Medicine 2.0 conference in London. 

PMID- 25075247
TI  - Employee and family assistance video counseling program: a post launch
      retrospective comparison with in-person counseling outcomes.
AB  - BACKGROUND: Access to technologically mediated information and services under the
      umbrella of mental and physical health has become increasingly available to
      clients via Internet modalities, according to a recent study. In May 2010, video
      counseling was added to the counseling services offered through the Employee and
      Family Assistance Program at Shepell.fgi as a pilot project with a full
      operational launch in September 2011. OBJECTIVE: The objective of this study was
      to conduct a retrospective post launch examination of the video counseling
      service through an analysis of the reported clinical outcomes of video and in
      person counseling modalities. METHODS: A chronological sample of 68 video
      counseling (VC) cases and 68 in-person (IP) cases were collected from a pool of
      client clinical files closed in 2012. To minimize the variables impacting the
      study and maintain as much clinical continuity as possible, the IP and the VC
      clients must have attended clinical sessions with any one of six counselors who
      provided both the VC and the IP services. The study compared the two counseling
      modalities along the following data points (see glossary of terms): (1) client
      demographic profiles (eg, age, gender, whether the sessions involved individuals
      or conjoint sessions with couples or families, etc), (2) presenting issue, (3)
      average session hours, (4) client rating of session helpfulness, (5) rates of
      goal completion, (6) client withdrawal rates, (7) no show and late cancellation
      rates, and (8) pre/post client self-assessment. Specific to VC, we examined
      client geographic location. RESULTS: Data analysis demonstrates that the VC and
      the IP showed a similar representation of presenting issues with nearly identical
      outcomes for client ratings of session helpfulness, rates of goal completion,
      pre/post client self-assessment, average session duration, and client geographic
      location. There were no statistically significant differences in the rates of
      withdrawal from counseling, no shows, and late cancellations between the VC and
      the IP counseling. The statistical analysis of the data was done on SPSS
      statistical software using 2-sample and pairwise comparison t tests at a 95%
      level of significance. CONCLUSIONS: Based on the study, VC and IP show similar
      outcomes in terms of client rating of session and goal attainment.

PMID- 25075248
TI  - Health information on the web and consumers' perspectives on health
      professionals' responses to information exchange.
AB  - BACKGROUND: Health information technology, which is sometimes referred to as
      informaticization of medicine, is changing the extent to which patients become
      competent producers of their own health by enabling them access to health
      information anytime and anywhere. OBJECTIVE: This research provides preliminary
      information on users' perceptions of the extent to which use of the Internet for
      health information impacts medical encounters. We specifically explored the
      following questions: (1) To what extent perceptions of positive or negative
      changes in medical encounters are associated with sociodemographic background of
      online health information seekers, and how often the Internet information is
      discussed with providers? (2) To what extent is there an association between
      perceived changes in medical encounters and frequency of referring to the
      Internet during medical encounters? (3) To what extent is there an association
      between sociodemographic background of online health information users and
      frequency of discussing of the Internet information with providers? METHODS: The
      data for this study was derived from a national sampling of online health and
      medical information users who participated in the Study of Health and Medical
      Information in Cyberspace-Survey of User Perceptions (N=710). This study used a
      nationally representative online research panel of the US adults maintained by
      the Knowledge Networks. Analysis of variance (ANOVA), chi-square, and t tests
      were performed to examine the data. RESULTS: Although Internet sources allow
      people the opportunity to gather health or medical information, discussion of
      this information was not a very common activity. It is noteworthy that half of
      the sample never or rarely discussed health/medical information obtained from
      Internet sources with health professionals. Chi-square analyses revealed that
      discussion of online health information with providers were associated with
      education, income, and marital status. We also found that discussion of the
      Internet information mostly promotes better physician-patient interactions.
      Analyses with post-hoc tests identified that perceived changes in medical
      encounters were associated with age, education, and income. However, 9.1%
      (64/703) of our respondents strongly agreed that the interactions with their
      providers have been strained. T test analyses showed that marital status, race,
      and gender were not significant. CONCLUSIONS: Embracing new technologies, and
      adapting to changing roles and relationships in delivery of medical care are
      critical to effective delivery of patient-centered care. Health professionals
      could also guide patients on how to evaluate information and where to access to
      reliable and accurate information.

PMID- 25075249
TI  - Border-ownership coding.

PMID- 25075250
TI  - Epithelial and stromal expression of miRNAs during prostate cancer progression.
AB  - Global microRNA (miRNA) profile may predict prostate cancer (PCa) behaviors. In
      this study, we examined global miRNA expression by miRNA profiling as well as
      specific miRNA expression levels in PCa epithelium and stroma by in situ
      hybridization (ISH) and correlated with various clinicopathological features. We
      first performed comprehensive miRNA profiling on 27 macrodissected cases of PCa
      by miRNA microarray. A total of 299 miRNAs were significantly dysregulated in
      high grade and advanced stage PCa. We demonstrated that PCa can be readily
      classified into high grade/stage and low-grade/stage groups by its global miRNA
      expression profile. Next, we examined the expression of several selected
      dysregulated miRNAs, including let-7c, miR-21, miR-27a, miR-30c, and miR-219, in
      PCa by ISH. The levels of miRNA expression in epithelial and stromal cells were
      scored semiquantitatively and compared with clinicopathological features,
      including age, race, Gleason score, stage, PSA recurrence, metastasis, hormone
      resistance and survival. We found that the expression of miR-30c and miR-219 were
      significantly down-regulated in PCa. miR-21 and miR-30c were significantly down
      regulated in PCa in African Americans compared to Caucasian Americans. In
      addition, down-regulation of let-7c, miR-21, miR-30c, and miR-219 are associated
      with metastatic disease. Furthermore, down-regulation of miR-30c and let-7c are
      significantly associated with androgen-dependent PCa. In PCa stromal cells, let
      7c downregulation is significantly associated with extraprostatic extension. Our
      data suggest that selected miRNAs may serve as potential biomarkers to predict
      cancer progression. 

PMID- 25075251
TI  - Insights on the CXCL12-CXCR4 axis in hepatocellular carcinoma carcinogenesis.
AB  - Chemokines, a group of small chemotactic cytokines, and their G-protein-coupled
      receptors were originally identified for their ability to mediate various pro-
      and anti-inflammatory responses. Beyond the influence of chemokines and their
      cognate receptors in several inflammatory diseases, several malignancies have
      been shown to be dependent of chemokines for progression, tumor growth, cellular
      migration and invasion, and angiogenesis; those later facilitating the
      development of distant metastases. In hepatocellular carcinoma (HCC), chemokines
      were shown to affect leukocyte recruitment, neovascularization and tumor
      progression. CXCL12 (stromal-derived factor 1 alpha- SDF-1) is the primary ligand
      for the seven transmembrane G-protein coupled receptor CXCR4. The CXCR4/CXCL12
      axis exerts a variety of functions at different steps of HCC tumor progression,
      using autocrine and/or paracrine mechanisms to sustain tumor cell growth, to
      induce angiogenesis and to facilitate tumor escape through evasion of immune
      surveillance. In this review, we have comprehensively described the role of
      CXCR4/CXCL12 in HCC and also investigated the role of CXCR7, an alternative
      receptors that also binds CXCL12 with potentially distinct downstream effects.
      Preclinical data converge to demonstrate that inhibition of the CXCR4/CXCL12 axis
      may lead to direct inhibition of tumor migration, invasion, and metastases. This
      pathway is under investigation to identify potential novel treatments in HCC and
      other cancers. However, one of the major challenges faced in this emerging field
      targeting the CXCR4/CXCL12 signaling pathway, is the translation of current
      knowledge into the design and development of effective inhibitors of CXCR4 and/or
      CXCL12 for cancer therapy. 

PMID- 25075252
TI  - Sumoylation modulates oxidative stress relevant to the viability and
      functionality of pancreatic beta cells.
AB  - Sumoylation is an evolutionarily conserved regulatory mechanism to play an
      important role in various cellular processes through modulation of protein
      localization, stability and functionality. Recent studies including ours have
      consistently demonstrated that sumoylation provides protection for cells against
      oxidative stress. Given that pancreatic beta cells are a vulnerable target of
      oxidative stress, we thus in this minireview, updated the advancement of
      sumoylation in the regulation of ROS generation, and discussed its impact on
      several critical signaling pathways relevant to beta cells against oxidative
      stress and maintenance of functionality. Specifically, we bring together how
      sumoylation represses intracellular ROS formation, and protects beta cells
      against oxidative stress through regulating IkappaB/NFkappaB, JNK/c-Jun, and
      Maf/Nrf2 pathways. The tight implication of sumoylation in oxidative stress
      reflects that it could be an essential mechanism for beta cells to adapt to the
      detrimental cellular microenvironment. 

PMID- 25075253
TI  - S6K1 promotes invasiveness of breast cancer cells in a model of metastasis of
      triple-negative breast cancer.
AB  - Breast cancer is the second-leading cause of oncology-related death in US women.
      Of all invasive breast cancers, patients with tumors lacking expression of the
      estrogen and progesterone hormone receptors and overexpression of human epidermal
      growth factor receptor 2 have the poorest clinical prognosis. These referred to
      as triple-negative breast cancer (TNBC) represent an aggressive form of disease
      that is marked by early-onset metastasis, high tumor recurrence rate, and low
      overall survival during the first three years post-diagnosis. In this report, we
      discuss a novel model of early-onset TNBC metastasis to bone and lungs, derived
      from MDA-MB-231 cells. Breast cancer cells injected intravenously produced rapid,
      osteolytic metastases in long bones and spines of athymic nude mice, with
      concurrent metastasis to lungs, liver, and soft tissues. From the bone
      metastases, we developed a highly metastatic luciferase-tagged cell line variant
      named MDA-231-LUC Met. In this report, we demonstrate that the Akt/mTOR/S6K1 axis
      is hyperactivated in these cells, leading to a dramatic increase in
      phosphorylation of S6 ribosomal protein at Ser235/236. Lastly, we provide
      evidence that inhibition of the furthest downstream kinase in the mTOR pathway,
      S6K1, with a highly specific inhibitor PF-4708671 inhibits cell migration, and
      thus may provide a potent anti-metastatic adjuvant therapy approach. 

PMID- 25075254
TI  - Desferrioxamine regulates HIF-1 alpha expression in neonatal rat brain after
      hypoxia-ischemia.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) promotes cell survival after hypoxia
      ischemia by regulating its target genes. Desferrioxamine (DFO) has been found to
      up-regulate HIF-1alpha expression in ischemia brain injury. However, the
      signaling pathway to mediate this regulation remains unclear in neonatal hypoxia
      ischemia brain damage (HIBD). Since phosphoinositide 3-kinase (PI3K/Akt) pathway
      and extracellular signal-related protein kinase pathway (Erk1/2 MAPK) have proven
      to be involved in the regulation of HIF-1alpha in neonatal rat brain after
      hypoxia-ischemia (HI), we hypothesized that DFO might regulate HIF-1alpha by
      activating PI3K/Akt and Erk1/2 MAPK pathways in developing rat brain after HI. To
      test this hypothesis, we subjected postnatal day 10 rats to DFO intraperitoneal
      injection 30 min before HI. Rat brains were collected to detect the expression of
      HIF-1alpha and its target gene VEGF, as well as PI3K/Akt and Erk1/2 MAPK using
      Western blot analysis. We found that the expression of HIF-1alpha, VEGF, and p
      Erk1/2 was significantly upregulated and peaked at 4 h after HI in DFO treated
      group, with higher level and earlier peak time than control group. However, the
      expression of p-Akt was unchanged in DFO treated group compared with control
      group. Our findings suggest that DFO might up-regulate HIF-1alpha and its target
      gene VEGF through Erk1/2 MAPK pathway in the developing rat brain after HI. 

PMID- 25075255
TI  - Up-regulation of microRNA-10b is associated with the development of breast cancer
      brain metastasis.
AB  - Brain metastases from primary breast cancer are difficult to treat and associated
      with poor prognosis. Our understanding of the molecular basis for the development
      of such cancers is sparse. We hypothesized that the pro-metastatic microRNA-10b
      (miR-10b) plays a role in breast cancer brain metastasis. The study cohort
      comprised of twenty patients with breast cancer and brain metastasis as well as
      ten control patients (age, stage, and follow-up matched) with breast cancer
      without brain metastasis. All cases were microscopically reviewed to select tumor
      blocks with >50% tumor cells. RNA was extracted from formalin fixed paraffin
      embedded (FFPE) tumor tissue blocks. Expression of miR-10b was analyzed using qRT
      PCR. The relevance of miR-10b expression was also tested using human breast
      cancer cell lines. An increased expression of miR-10b was noted in the primary
      breast cancer specimens of patients who subsequently developed brain metastasis,
      compared to those who did not. miR-10b also increased the invasive potential of
      breast cancer cells in vitro. Wilcoxon signed rank test revealed a statistically
      significant difference between the paired tumors from breast cancers and brain
      metastasis (p <0.001). Increased expression of miR-10b appears to be associated
      with breast cancer brain metastasis. These findings are clinically relevant since
      miR-10b could serve as a prognostic and/or therapeutic target for anti-metastatic
      therapy. Identifying molecular signatures of primary breast cancers which have a
      propensity for brain metastasis is critical for designing novel therapies to
      counter the development of brain metastasis in patients diagnosed with breast
      cancer. 

PMID- 25075256
TI  - Prognostic value of miR-221-3p, miR-342-3p and miR-491-5p expression in colon
      cancer.
AB  - Increasing evidence has demonstrated that microRNAs (miRNAs) are involved in
      colon cancer initiation and progression, and may serve as diagnostic and
      prognostic biomarkers for colon cancer. Here, we investigated the levels of miR-9
      1, miR-203-3p, miR-221-3p, miR-342-3p, miR-491-5p and miR-503-5p in 90 pairs of
      colon cancer and adjacent normal tissues, and explored the relationship between
      their expression and clinical outcome of colon cancer. Five miRNAs (miR-203-3p,
      miR-221-3p, miR-342-3p, miR-491-5p and miR-503-5p) were dysregulated in colon
      cancer tissue (P < 0.05). The levels of miR-503-5p in larger tumors (>= 6 cm)
      were higher than those in smaller ones (< 6 cm) (P = 0.031), while the levels of
      miR-203-3p and miR-491-5p in patients aged 70 years and older were higher than
      those in patients aged younger than 70 years (P = 0.019 and 0.049, respectively).
      The high levels of miR-221-3p (HR = 2.416, 95% CI 1.314-4.445, P = 0.005), miR
      342-3p (HR = 1.807, 95% CI 1.003-3.253, P = 0.049) and miR-491-5p (HR = 1.868,
      95% CI 1.032-3.384, P = 0.039) were significantly associated with worse survival
      time. Moreover, combination analysis of miR-221-3p, miR-342-3p and miR-491-5p
      expression revealed that patients with 3 highly expressed miRNAs had lower
      survival rates compared with those with zero-to-two highly expressed miRNAs (HR =
      2.100, 95% CI 1.157-3.813, P = 0.015), especially those with TNM stages I and II
      (HR = 4.204,95% CI 1.762-10.030, P = 0.001). Our results suggest that the three
      miRNA signature may help doctors better predict prognosis and guide treatment
      decisions for colon cancer. 

PMID- 25075257
TI  - Improving population representation through geographic health information
      systems: mapping the MURDOCK study.
AB  - This paper highlights methods for using geospatial analysis to assess, enhance,
      and improve recruitment efforts to ensure representativeness in study
      populations. We apply these methods to the Measurement to Understand
      Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) study, a
      longitudinal population health study focused on the city of Kannapolis and
      Cabarrus County, NC. Although efforts have been made to recruit a participant
      registry that is representative of the 18 ZIP code catchment region inclusive of
      Cabarrus County and Kannapolis, bias in such recruitment is inevitable.
      Participants in the MURDOCK study are geospatially referenced at entry, providing
      information that can be used to monitor and guide recruitment efforts. MURDOCK
      participant population representativeness was assessed using chi-squared tests to
      compare the MURDOCK population with 2010 Census data, relative to both the entire
      18 ZIP code catchment area and for individual Census tracts. A logistic
      regression model was fit to characterize Census tracts with low recruitment,
      defined by fewer than 56 participants from that tract. The distance to the site
      at which participants enrolled was calculated, and median distance to enrollment
      site was used in the logistic regression. Tracts with low recruitment rates
      contained higher minority and younger populations, suggesting specific strategies
      for improving recruitment in these areas. Areal units farther away from
      enrollment sites were also not well-sampled, despite being in the specified study
      area, indicating that distance traveled to enrollment may be a barrier. These
      results have implications for targeting recruitment efforts and representative
      samples more generally, including in other population-based studies. 

PMID- 25075258
TI  - Improved peripheral nerve regeneration with sustained release nerve growth factor
      microspheres in small gap tubulization.
AB  - OBJECTIVE: To evaluate the long-term results of the use of nerve growth factor
      (NGF)-loaded poly-D, L-lactide-co-glycolide (PLGA) microspheres for improve nerve
      regeneration with small gap tubulization. METHODS: NGF microspheres were prepared
      by a modified W/O/W emulsion solvent evaporation method. Forty-eight male SD rats
      were separated into 4 groups and received a chitin conduit to bridge a sciatic
      nerve injury left a 2 mm gap. Saline (Group A), 20 ng/ml NGF solution (Group B),
      blank PLGA microspheres (Group C), or 40 ng/ml NGF-loaded microspheres (Group D)
      was injected in the gap. Each group had two study endpoints, 3 months subgroup
      and 1 year subgroup. RESULTS: The myelinated fiber count at 2 mm distal to the
      conduit at 1 year was slightly less than at 3 months in all groups (P>0.05).
      However, the maturity of the myelinated nerves at 1 year was obviously improved.
      The fiber count, myelin sheath thickness, axon area of NGF microsphere group were
      significantly higher than the saline groups at 3 months (P=0.05, P<0.05, and
      P<0.05, respectively). The SFI was significantly improved in NGF microspheres
      group compared to the saline group and NGF solution group at 1 year (P<0.05, and
      P<0.05, respectively). CONCLUSIONS: The results demonstrated that the release of
      NGF microspheres in small gap tubulization benefit on peripheral nerve injury
      facilitated nerve regeneration histologically, especially for the maturity of
      early regenerative nerve fibers and also had an effect on functional recovery in
      the long term.

PMID- 25075259
TI  - THE EFFECT OF THE C-LEG KNEE PROSTHESIS ON SENSORY DEPENDENCY AND FALLS DURING
      SENSORY ORGANIZATION TESTING.
AB  - A mechanistic explanation for previously observed safety improvements with
      microprocessor-controlled prosthetic knees is needed. A repeated measures design
      of 15 subjects with unilateral transfemoral amputation was used to assess changes
      between baseline use of their standard of care, mechanical pros-theses, and a C
      Leg microprocessor-controlled prosthetic knee. The primary outcome measures were
      sensory dependency scores for somatosensory, visual, vestibular, and visual
      preference, which were calculated based on a Sensory Organization Test. Falls
      during posturographic assessment were also recorded. Somatosensory system
      dependency significantly increased (p = 0.047) while using the C-Leg compared to
      a nonmicroprocessor prosthetic knee (NMPK). Reliance on visual with vestibular
      input and reliance on vestibular input alone were not significantly increased
      with C-Leg use (p = 0.41 and p = 0.15, respectively). When utilizing the C-Leg,
      there was a significant reduction in the average number of falls (p = 0.03).
      Hence, increased reliance on somatosensory input is a possible explanation for
      improved balance with use of a microprocessor prosthetic knee (MPK).

PMID- 25075261
TI  - Radiant energy during infrared neural stimulation at the target structure.
AB  - Infrared neural stimulation (INS) describes a method, by which an infrared laser
      is used to stimulate neurons. The major benefit of INS over stimulating neurons
      with electrical current is its spatial selectivity. To translate the technique
      into a clinical application it is important to know the energy required to
      stimulate the neural structure. With this study we provide measurements of the
      radiant exposure, at the target structure that is required to stimulate the
      auditory neurons. Flat polished fibers were inserted into scala tympani so that
      the spiral ganglion was in front of the optical fiber. Angle polished fibers were
      inserted along scala tympani, and rotating the beveled surface of the fiber
      allowed the radiation beam to be directed perpendicular to the spiral ganglion.
      The radiant exposure for stimulation at the modiolus for flat and angle polished
      fibers averaged 6.78+/-2.15 mJ/cm2. With the angle polished fibers, a 90 degrees 
      change in the orientation of the optical beam from an orientation that resulted
      in an INS-evoked maximum response, resulted in a 50% drop in the response
      amplitude. When the orientation of the beam was changed by 180 degrees , such
      that it was directed opposite to the orientation with the maxima, minimum
      response amplitude was observed.

PMID- 25075260
TI  - Infrared neural stimulation in the cochlea.
AB  - The application of photonics to manipulate and stimulate neurons and to study
      neural networks has gained momentum over the last decade. Two general methods
      have been used: the genetic expression of light or temperature sensitive ion
      channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and
      the direct stimulation of neurons using infrared radiation (Infrared Neural
      Stimulation, INS). Both approaches have their strengths and challenges, which are
      well understood with a profound understanding of the light tissue interaction(s).
      This paper compares the opportunities of the methods for the use in cochlear
      prostheses. Ample data are already available on the stimulation of the cochlea
      with INS. The data show that the stimulation is selective, feasible at rates that
      would be sufficient to encode acoustic information and may be beneficial over
      conventional pulsed electrical stimulation. A third approach, using lasers in
      stress confinement to generate pressure waves and to stimulate the functional
      cochlea mechanically will also be discussed.

PMID- 25075262
TI  - Masking of Infrared Neural Stimulation (INS) in hearing and deaf guinea pigs.
AB  - Spatial selective infrared neural stimulation has potential to improve neural
      prostheses, including cochlear implants. The heating of a confined target volume
      depolarizes the cell membrane and results in an action potential. Tissue heating
      may also results in thermal damage or the generation of a stress relaxation wave.
      Stress relaxation waves may result in a direct mechanical stimulation of
      remaining hair cells in the cochlea, so called optophony. Data are presented that
      quantify the effect of an acoustical stimulus (noise masker) on the response
      obtained with INS in normal hearing, acutely deafened, and chronic deaf animals.
      While in normal hearing animals an acoustic masker can reduce the response to
      INS, in acutely deafened animals the masking effect is reduced, and in chronic
      deaf animals this effect has not been detected. The responses to INS remain
      stable following the different degrees of cochlear damage.

PMID- 25075263
TI  - Two approximations for the geometric model of signal amplification in an electron
      multiplying charge-coupled device detector.
AB  - The extraction of information from images acquired under low light conditions
      represents a common task in diverse disciplines. In single molecule microscopy,
      for example, techniques for superresolution image reconstruction depend on the
      accurate estimation of the locations of individual particles from generally low
      light images. In order to estimate a quantity of interest with high accuracy,
      however, an appropriate model for the image data is needed. To this end, we
      previously introduced a data model for an image that is acquired using the
      electron-multiplying charge-coupled device (EMCCD) detector, a technology of
      choice for low light imaging due to its ability to amplify weak signals
      significantly above its readout noise floor. Specifically, we proposed the use of
      a geometrically multiplied branching process to model the EMCCD detector's
      stochastic signal amplification. Geometric multiplication, however, can be
      computationally expensive and challenging to work with analytically. We therefore
      describe here two approximations for geometric multiplication that can be used
      instead. The high gain approximation is appropriate when a high level of signal
      amplification is used, a scenario which corresponds to the typical usage of an
      EMCCD detector. It is an accurate approximation that is computationally more
      efficient, and can be used to perform maximum likelihood estimation on EMCCD
      image data. In contrast, the Gaussian approximation is applicable at all levels
      of signal amplification, but is only accurate when the initial signal to be
      amplified is relatively large. As we demonstrate, it can importantly facilitate
      the analysis of an information-theoretic quantity called the noise coefficient.

PMID- 25075264
TI  - Responses to amplitude modulated infrared stimuli in the guinea pig inferior
      colliculus.
AB  - Responses of units in the central nucleus of the inferior colliculus of the
      guinea pig were recorded with tungsten electrodes. The set of data presented here
      is limited to high stimulus levels. The effect of changing the modulation
      frequency and the modulation depth was explored for acoustic and laser stimuli.
      The selected units responded to sinusoidal amplitude modulated (AM) tones, AM
      trains of clicks, and AM trains of laser pulses with a modulation of their spike
      discharge. At modulation frequencies of 20 Hz, some units tended to respond with
      40 Hz to the acoustic stimuli, but only at 20 Hz for the trains of laser pulses.
      For all modes of stimulation the responses revealed a dominant response to the
      first cycle of the modulation, with decreasing number of action potential during
      successive cycles. While amplitude modulated tone bursts and amplitude modulated
      trains of acoustic clicks showed similar patterns, the response to trains of
      laser pulses was different.

PMID- 25075265
TI  - Parsing radiographs by integrating landmark set detection and multi-object active
      appearance models.
AB  - This work addresses the challenging problem of parsing 2D radiographs into
      salient anatomical regions such as the left and right lungs and the heart. We
      propose the integration of an automatic detection of a constellation of landmarks
      via rejection cascade classifiers and a learned geometric constellation subset
      detector model with a multi-object active appearance model (MO-AAM) initialized
      by the detected landmark constellation subset. Our main contribution is twofold.
      First, we propose a recovery method for false positive and negative landmarks
      which allows to handle extreme ranges of anatomical and pathological variability.
      Specifically we (1) recover false negative (missing) landmarks through the
      consensus of inferences from subsets of the detected landmarks, and (2) choose
      one from multiple false positives for the same landmark by learning Gaussian
      distributions for the relative location of each landmark. Second, we train a MO
      AAM using the true landmarks for the detectors and during test, initialize the
      model using the detected landmarks. Our model fitting allows simultaneous
      localization of multiple regions by encoding the shape and appearance information
      of multiple objects in a single model. The integration of landmark detection
      method and MO-AAM reduces mean distance error of the detected landmarks from
      20.0mm to 12.6mm. We assess our method using a database of scout CT scans from 80
      subjects with widely varying pathology.

PMID- 25075266
TI  - Energy-aware Activity Classification using Wearable Sensor Networks.
AB  - This paper presents implementation details, system characterization, and the
      performance of a wearable sensor network that was designed for human activity
      analysis. Specific machine learning mechanisms are implemented for recognizing a
      target set of activities with both out-of-body and on-body processing
      arrangements. Impacts of energy consumption by the on-body sensors are analyzed
      in terms of activity detection accuracy for out-of-body processing. Impacts of
      limited processing abilities for the on-body scenario are also characterized in
      terms of detection accuracy, by varying the background processing load in the
      sensor units. Impacts of varying number of sensors in terms of activity
      classification accuracy are also evaluated. Through a rigorous systems study, it
      is shown that an efficient human activity analytics system can be designed and
      operated even under energy and processing constraints of tiny on-body wearable
      sensors.

PMID- 25075267
TI  - Automated detection of remineralization in simulated enamel lesions with PS-OCT.
AB  - Previous in vitro and in vivo studies have demonstrated that polarization
      sensitive optical coherence tomography (PS-OCT) can be used to nondestructively
      image the subsurface structure and measure the thickness of the highly
      mineralized transparent surface zone of caries lesions. There are structural
      differences between active lesions and arrested lesions, and the surface layer
      thickness may correlate with activity of the lesion. The purpose of this study
      was to develop a method that can be used to automatically detect and measure the
      thickness of the transparent surface layer in PS-OCT images. Automated methods of
      analysis were used to measure the thickness of the transparent layer and the
      depth of the bovine enamel lesions produced using simulated caries models that
      emulate demineralization in the mouth. The transparent layer thickness measured
      with PS-OCT correlated well with polarization light microscopy (PLM) measurements
      of all regions (r2=0.9213). This study demonstrates that PS-OCT can automatically
      detect and measure thickness of the transparent layer formed due to
      remineralization in simulated caries lesions.

PMID- 25075268
TI  - A stereoscopic system for viewing the temporal evolution of brain activity
      clusters in response to linguistic stimuli.
AB  - In this paper, we present a novel application, 3D+Time Brain View, for the
      stereoscopic visualization of functional Magnetic Resonance Imaging (fMRI) data
      gathered from participants exposed to unfamiliar spoken languages. An analysis
      technique based on Independent Component Analysis (ICA) is used to identify
      statistically significant clusters of brain activity and their changes over time
      during different testing sessions. That is, our system illustrates the temporal
      evolution of participants' brain activity as they are introduced to a foreign
      language through displaying these clusters as they change over time. The raw fMRI
      data is presented as a stereoscopic pair in an immersive environment utilizing
      passive stereo rendering. The clusters are presented using a ray casting
      technique for volume rendering. Our system incorporates the temporal information
      and the results of the ICA into the stereoscopic 3D rendering, making it easier
      for domain experts to explore and analyze the data.

PMID- 25075269
TI  - Smoothing fields of weighted collections with applications to diffusion MRI
      processing.
AB  - Using modern diffusion weighted magnetic resonance imaging protocols, the
      orientations of multiple neuronal fiber tracts within each voxel can be
      estimated. Further analysis of these populations, including application of fiber
      tracking and tract segmentation methods, is often hindered by lack of spatial
      smoothness of the estimated orientations. For example, a single noisy voxel can
      cause a fiber tracking method to switch tracts in a simple crossing tract
      geometry. In this work, a generalized spatial smoothing framework that handles
      multiple orientations as well as their fractional contributions within each voxel
      is proposed. The approach estimates an optimal fuzzy correspondence of
      orientations and fractional contributions between voxels and smooths only between
      these correspondences. Avoiding a requirement to obtain exact correspondences of
      orientations reduces smoothing anomalies due to propagation of erroneous
      correspondences around noisy voxels. Phantom experiments are used to demonstrate
      both visual and quantitative improvements in postprocessing steps. Improvement
      over smoothing in the measurement domain is also demonstrated using both phantoms
      and in vivo human data.

PMID- 25075270
TI  - Breast density and parenchymal texture measures as potential risk factors for
      Estrogen-Receptor positive breast cancer.
AB  - Accurate assessment of a woman's risk to develop specific subtypes of breast
      cancer is critical for appropriate utilization of chemopreventative measures,
      such as with tamoxifen in preventing estrogen-receptor positive breast cancer. In
      this context, we investigate quantitative measures of breast density and
      parenchymal texture, measures of glandular tissue content and tissue structure,
      as risk factors for estrogen-receptor positive (ER+) breast cancer. Mediolateral
      oblique (MLO) view digital mammograms of the contralateral breast from 106 women
      with unilateral invasive breast cancer were retrospectively analyzed. Breast
      density and parenchymal texture were analyzed via fully-automated software.
      Logistic regression with feature selection and was performed to predict ER+
      versus ER- cancer status. A combined model considering all imaging measures
      extracted was compared to baseline models consisting of density-alone and texture
      alone features. Area under the curve (AUC) of the receiver operating
      characteristic (ROC) and Delong's test were used to compare the models'
      discriminatory capacity for receptor status. The density-alone model had a
      discriminatory capacity of 0.62 AUC (p=0.05). The texture-alone model had a
      higher discriminatory capacity of 0.70 AUC (p=0.001), which was not significantly
      different compared to the density-alone model (p=0.37). In contrast the combined
      density-texture logistic regression model had a discriminatory capacity of 0.82
      AUC (p<0.001), which was statistically significantly higher than both the density
      alone (p<0.001) and texture-alone regression models (p=0.04). The combination of
      breast density and texture measures may have the potential to identify women
      specifically at risk for estrogen-receptor positive breast cancer and could be
      useful in triaging women into appropriate risk-reduction strategies.

PMID- 25075271
TI  - Identifying MRI markers to evaluate early treatment related changes post laser
      ablation for cancer pain management.
AB  - Laser interstitial thermal therapy (LITT) has recently emerged as a new treatment
      modality for cancer pain management that targets the cingulum (pain center in the
      brain), and has shown promise over radio-frequency (RF) based ablation which is
      reported to provide temporary relief. One of the major advantages enjoyed by LITT
      is its compatibility with magnetic resonance imaging (MRI), allowing for high
      resolution in vivo imaging to be used in LITT procedures. Since laser ablation
      for pain management is currently exploratory and is only performed at a few
      centers worldwide, its short-, and long-term effects on the cingulum are
      currently unknown. Traditionally treatment effects are evaluated by monitoring
      changes in volume of the ablation zone post-treatment. However, this is sub
      optimal since it involves evaluating a single global parameter (volume) to detect
      changes pre-, and post-MRI. Additionally, the qualitative observations of LITT
      related changes on multi-parametric MRI (MP-MRI) do not specifically address
      differentiation between the appearance of treatment related changes (edema,
      necrosis) from recurrence of the disease (pain recurrence). In this work, we
      explore the utility of computer extracted texture descriptors on MP-MRI to
      capture early treatment related changes on a per-voxel basis by extracting
      quantitative relationships that may allow for an in-depth understanding of tissue
      response to LITT on MRI, subtle changes that may not be appreciable on original
      MR intensities. The second objective of this work is to investigate the efficacy
      of different MRI protocols in accurately capturing treatment related changes
      within and outside the ablation zone post-LITT. A retrospective cohort of studies
      comprising pre- and 24-hour post-LITT 3 Tesla T1-weighted (T1w), T2w, T2-GRE, and
      T2-FLAIR acquisitions was considered. Our scheme involved (1) inter-protocol as
      well as inter-acquisition affine registration of pre- and post-LITT MRI, (2)
      quantitation of MRI parameters by correcting for intensity drift in order to
      examine tissue-specific response, and (3) quantification of MRI maps via texture
      and intensity features to evaluate changes in MR markers pre- and post-LITT. A
      total of 78 texture features comprising of non-steerable and steerable gradient
      and second order statistical features were extracted from pre- and post-LITT MP
      MRI on a per-voxel basis. Quantitative, voxel-wise comparison of the changes in
      MRI texture features between pre-, and post-LITT MRI indicate that (a) steerable
      and non-steerable gradient texture features were highly sensitive as well as
      specific in predicting subtle micro-architectural changes within and around the
      ablation zone pre- and post-LITT, (b) FLAIR was identified as the most sensitive
      MRI protocol in identifying early treatment changes yielding a normalized
      percentage change of 360% within the ablation zone relative to its pre-LITT
      value, and (c) GRE was identified as the most sensitive MRI protocol in
      quantifying changes outside the ablation zone post-LITT. Our preliminary results
      thus indicate great potential for non-invasive computerized MRI features in
      determining localized micro-architectural focal treatment related changes post
      LITT.

PMID- 25075272
TI  - Dysregulation of matricellular proteins is an early signature of pathology in
      laminin-deficient muscular dystrophy.
AB  - BACKGROUND: MDC1A is a congenital neuromuscular disorder with developmentally
      complex and progressive pathologies that results from a deficiency in the protein
      laminin alpha2. MDC1A is associated with a multitude of pathologies, including
      increased apoptosis, inflammation and fibrosis. In order to assess and treat a
      complicated disease such as MDC1A, we must understand the natural history of the
      disease so that we can identify early disease drivers and pinpoint critical time
      periods for implementing potential therapies. RESULTS: We found that DyW mice
      show significantly impaired myogenesis and high levels of apoptosis as early as
      postnatal week 1. We also saw a surge of inflammatory response at the first week,
      marked by high levels of infiltrating macrophages, nuclear factor kappaB
      activation, osteopontin expression and overexpression of inflammatory cytokines.
      Fibrosis markers and related pathways were also observed to be elevated
      throughout early postnatal development in these mice, including periostin,
      collagen and fibronectin gene expression, as well as transforming growth factor
      beta signaling. Interestingly, fibronectin was found to be the predominant
      fibrous protein of the extracellular matrix in early postnatal development.
      Lastly, we observed upregulation in various genes related to angiotensin
      signaling. METHODS: We sought out to examine the dysregulation of various
      pathways throughout early development (postnatal weeks 1-4) in the DyW mouse, the
      most commonly used mouse model of laminin-deficient muscular dystrophy. Muscle
      function tests (stand-ups and retractions) as well as gene (qRT-PCR) and protein
      levels (western blot, ELISA), histology (H&E, picrosirius red staining) and
      immunohistochemistry (fibronectin, TUNEL assay) were used to assess dysregulation
      of matricelluar protieins. CONCLUSIONS: Our results implicate the involvement of
      multiple signaling pathways in driving the earliest stages of pathology in DyW
      mice. As opposed to classical dystrophies, such as Duchenne muscular dystrophy,
      the dysregulation of various matricellular proteins appears to be a distinct
      feature of the early progression of DyW pathology. On the basis of our results,
      we believe that therapies that may reduce apoptosis and stabilize the homeostasis
      of extracellular matrix proteins may have increased efficacy if started at a very
      early age.

PMID- 25075273
TI  - Transitions from hospital to community care: the role of patient-provider
      language concordance.
AB  - BACKGROUND: Cultural and language discordance between patients and providers
      constitutes a significant challenge to provision of quality healthcare. This
      study aims to evaluate minority patients' discharge from hospital to community
      care, specifically examining the relationship between patient-provider language
      concordance and the quality of transitional care. METHODS: This was a multi
      method prospective study of care transitions of 92 patients: native Hebrew,
      Russian or Arabic speakers, with a pre-discharge questionnaire and structured
      observations examining discharge preparation from a large Israeli teaching
      hospital. Two weeks post-discharge patients were surveyed by phone, on the
      transition from hospital to community care (the Care Transition Measure (CTM-15,
      0-100 scale)) and on the primary-care post-discharge visit. RESULTS: Overall,
      ratings on the CTM indicated fair quality of the transition process (scores of
      51.8 to 58.8). Patient-provider language concordance was present in 49% of
      minority patients' discharge briefings. Language concordance was associated with
      higher CTM scores among minority groups (64.1 in language-concordant versus 49.8
      in non-language-concordant discharges, P <0.001). Other aspects significantly
      associated with CTM scores: extent of discharge explanations (P <0.05), quality
      of discharge briefing (P <0.001), and post-discharge explanations by the primary
      care physician (P <0.01). CONCLUSION: Language-concordant care, coupled with
      extensive discharge briefings and post-discharge explanations for ongoing care,
      are important contributors to the quality of care transitions of ethnic minority
      patients.

PMID- 25075274
TI  - The role of medical schools in promoting social accountability through shared
      decision-making.
AB  - Reducing health inequalities and enhancing the social accountability of medical
      students and physicians is a challenge acknowledged by medical educators and
      professionals. It is usually perceived as a macro-level, community type
      intervention. This commentary suggests a different approach, an interpersonal way
      to decrease inequality and asymmetry in power relations to improve medical
      decisions and care. Shared decision-making practices are suggested as a model
      that requires building partnership, bi-directional sharing of information,
      empowering patients and enhancing tailored health care decisions. To increase the
      implementation of shared decision-making practices in Israel, an official policy
      needs to be established to encourage the investment of resources towards helping
      educators, researchers, and practitioners translate and integrate it into daily
      practice. Special efforts should be invested in medical education initiatives to
      train medical students and residents in SDM practices. 

PMID- 25075275
TI  - Increased default mode network activity in socially anxious individuals during
      reward processing.
AB  - BACKGROUND: Social anxiety has been associated with potentiated negative affect
      and, more recently, with diminished positive affect. It is unclear how these
      alterations in negative and positive affect are represented neurally in socially
      anxious individuals and, further, whether they generalize to non-social stimuli.
      To explore this, we used a monetary incentive paradigm to explore the association
      between social anxiety and both the anticipation and consumption of non-social
      incentives. Eighty-four individuals from a longitudinal community sample
      underwent functional magnetic resonance imaging (fMRI) while participating in a
      monetary incentive delay (MID) task. The MID task consisted of alternating cues
      indicating the potential to win or prevent losing varying amounts of money based
      on the speed of the participant's response. We examined whether self-reported
      levels of social anxiety, averaged across approximately 7 years of data,
      moderated brain activity when contrasting gain or loss cues with neutral cues
      during the anticipation and outcome phases of incentive processing. Whole brain
      analyses and analyses restricted to the ventral striatum for the anticipation
      phase and the medial prefrontal cortex for the outcome phase were conducted.
      RESULTS: Social anxiety did not associate with differences in hit rates or
      reaction times when responding to cues. Further, socially anxious individuals did
      not exhibit decreased ventral striatum activity during anticipation of gains or
      decreased MPFC activity during the outcome of gain trials, contrary to
      expectations based on literature indicating blunted positive affect in social
      anxiety. Instead, social anxiety showed positive associations with extensive
      regions implicated in default mode network activity (for example, precuneus,
      posterior cingulate cortex, and parietal lobe) during anticipation and receipt of
      monetary gain. Social anxiety was further linked with decreased activity in the
      ventral striatum during anticipation of monetary loss. CONCLUSIONS: Socially
      anxious individuals may increase default mode network activity during reward
      processing, suggesting high self-focused attention even in relation to
      potentially rewarding stimuli lacking explicit social connotations. Additionally,
      social anxiety may relate to decreased ventral striatum reactivity when
      anticipating potential losses.

PMID- 25075276
TI  - An EAACI "European Survey on Adverse Systemic Reactions in Allergen Immunotherapy
      (EASSI)": the methodology.
AB  - At present, there is no European report on clinically relevant systemic reactions
      due to the regular use of allergen immunotherapy (AIT), administered either
      subcutaneously or sublingually (SCIT and SLIT, respectively) outside clinical
      trials. Using an electronic survey and a "harmonised terminology" according to
      MedDRA, we aimed to prospectively collect systemic adverse reactions due to AIT
      from real life clinical settings. Under the framework of the EAACI, a team of
      European specialists in AIT, pharmacovigilance, epidemiology and drugs regulation
      set up a web-based prospective pilot survey to be conducted in three European
      countries (France, Germany and Spain). A designated "national coordinator" was
      responsible for following ethics requirements relative to each country and to
      select at least 30 doctors per country. Patients were recruited the same day they
      received their first dose of either SCIT or SLIT. Patient inclusion criteria
      were: adults and children, with IgE mediated pollen, house dust mite, Alternaria,
      and/or animal dander respiratory allergies who will initiate AIT. A list of 31
      symptoms terms were extracted from the MedDRA (Medical Dictionary for Regulatory
      Activities) dictionary to harmonize the reporting of all adverse systemic
      reactions in this survey. The SurveyMonkey(r) online instrument was used by
      participant doctors to submit information directly to a blinded central database.
      THREE QUESTIONNAIRES WERE GENERATED: i) the Doctor Questionnaire, ii) the Patient
      Questionnaire and iii) the Adverse Reaction Questionnaire. A handbook and a
      mistake report form were given to each doctor. In this paper, we describe the
      methodology followed.

PMID- 25075277
TI  - Amblyomma tapirellum  (Acari: Ixodidae) collected from tropical forest canopy.
AB  - Free-ranging ticks are widely known to be restricted to the ground level of
      vegetation. Here, we document the capture of the tick species Amblyomma
      tapirellum in light traps placed in the forest canopy of Barro Colorado Island,
      central Panama. A total of forty eight adults and three nymphs were removed from
      carbon dioxide-octenol baited CDC light traps suspended 20 meters above the
      ground during surveys for forest canopy mosquitoes. To our knowledge, this
      represents the first report of questing ticks from the canopy of tropical
      forests. Our finding suggests a novel ecological relationship between A.
      tapirellum and arboreal mammals, perhaps monkeys that come to the ground to drink
      or to feed on fallen fruits. 

PMID- 25075278
TI  - Mapping whole genome shotgun sequence and variant calling in mammalian species
      without their reference genomes.
AB  - Genomics research in mammals has produced reference genome sequences that are
      essential for identifying variation associated with disease.  High quality
      reference genome sequences are now available for humans, model species, and
      economically important agricultural animals.  Comparisons between these species
      have provided unique insights into mammalian gene function.  However, the number
      of species with reference genomes is small compared to those needed for studying
      molecular evolutionary relationships in the tree of life.  For example, among the
      even-toed ungulates there are approximately 300 species whose phylogenetic
      relationships have been calculated in the 10k trees project.  Only six of these
      have reference genomes:  cattle, swine, sheep, goat, water buffalo, and bison. 
      Although reference sequences will eventually be developed for additional hoof
      stock, the resources in terms of time, money, infrastructure and expertise
      required to develop a quality reference genome may be unattainable for most
      species for at least another decade.  In this work we mapped 35 Gb of next
      generation sequence data of a Katahdin sheep to its own species' reference genome
      ( Ovis aries Oar3.1) and to that of a species that diverged 15 to 30 million
      years ago ( Bos taurus UMD3.1).  In total, 56% of reads covered 76% of UMD3.1 to
      an average depth of 6.8 reads per site, 83 million variants were identified, of
      which 78 million were homozygous and likely represent interspecies nucleotide
      differences. Excluding genome repeat regions and sex chromosomes, approximately
      3.7 million heterozygous sites were identified in this animal vs. bovine UMD3.1,
      representing polymorphisms occurring in sheep.  Of these, 41% could be readily
      mapped to orthologous positions in ovine Oar3.1 with 80% corroborated as
      heterozygous.  These variant sites, identified via interspecies mapping could be
      used for comparative genomics, disease association studies, and ultimately to
      understand mammalian gene function. 

PMID- 25075279
TI  - Case Report: Pregnancy in a patient with recurrent glioblastoma.
AB  - We report the case of a woman with relapsed glioblastoma multiforme (GBM) who
      recently gave birth. She announced her pregnancy shortly after the sixth cycle of
      a dense regimen of temozolomide, prescribed for treating the first recurrence of
      glioblastoma. Three years ago, in April 2008, she had undergone gross total
      resection of a glioblastoma multiforme in the postcentral region of the right
      hemisphere and had subsequently received treatment according to the actual
      standard therapy consisting of radiotherapy up to 60 Gy with concomitant and
      adjuvant temozolomide. The complete amount of temozolomide given before this
      pregnancy was 20.9 mg/m (2). Nevertheless, she delivered a 1890 g child by
      caesarean section in the 32/6 week of pregnancy. The child showed no anomalies
      and is developing normally under close surveillance by paediatricians. 

PMID- 25075280
TI  - No psychological effect of color context in a low level vision task.
AB  - BACKGROUND: A remarkable series of recent papers have shown that colour can
      influence performance in cognitive tasks. In particular, they suggest that
      viewing a participant number printed in red ink or other red ancillary stimulus
      elements improves performance in tasks requiring local processing and impedes
      performance in tasks requiring global processing whilst the reverse is true for
      the colour blue. The tasks in these experiments require high level cognitive
      processing such as analogy solving or remote association tests and the chromatic
      effect on local vs. global processing is presumed to involve widespread
      activation of the autonomic nervous system. If this is the case, we might expect
      to see similar effects on all local vs. global task comparisons. To test this
      hypothesis, we asked whether chromatic cues also influence performance in tasks
      involving low level visual feature integration. METHODS: Subjects performed
      either local (contrast detection) or global (form detection) tasks on achromatic
      dynamic Glass pattern stimuli. Coloured instructions, target frames and fixation
      points were used to attempt to bias performance to different task types. Based on
      previous literature, we hypothesised that red cues would improve performance in
      the (local) contrast detection task but would impede performance in the (global)
      form detection task.  RESULTS: A two-way, repeated measures, analysis of
      covariance (2*2 ANCOVA) with gender as a covariate, revealed no influence of
      colour on either task, F(1,29) = 0.289, p = 0.595, partial eta (2) = 0.002.
      Additional analysis revealed no significant differences in only the first
      attempts of the tasks or in the improvement in performance between trials.
      DISCUSSION: We conclude that motivational processes elicited by colour perception
      do not influence neuronal signal processing in the early visual system, in stark
      contrast to their putative effects on processing in higher areas.

PMID- 25075281
TI  - Misleading hepatitis B testing in the setting of intravenous immunoglobulin.
AB  - Intravenous immunoglobulin (IVIG) is commonly used for a wide range of diagnoses,
      by multiple pediatric subspecialists. We report two cases of hepatitis B
      screening results post IVIG infusion, where positive anti-Hepatitis B core
      antigen serology tests indicated possible occult hepatitis infection, leading to
      a delay in care. However, serial antibody testing showed results consistent with
      the passive transfer of antibodies. 

PMID- 25075282
TI  - A close call: does the location of incision at cesarean delivery matter in
      patients with vasa previa? A case report.
AB  - We present here a case of vasa previa in a multipara, diagnosed at the time of
      her late second trimester ultrasonogram. The patient subsequently underwent an
      elective cesarean section after 37 weeks gestation, giving birth to a healthy
      child with an uneventful post-partum, neonatal and infant course. At the time of
      cesarean section, the incision was gradually deepened in layers through the
      myometrium by utmost care allowing the amniotic sac to protrude through the
      uterine incision hereby avoiding laceration of the vasa previa and its branches.
      Fetal exsanguination and a need for blood transfusion as well as a possible
      adverse neonatal course were therefore avoided. 

PMID- 25075283
TI  - Endovascular treatment of chronic mesenteric ischemia in an adolescent male: case
      report.
AB  - Chronic mesenteric ischemia (CMI) is a condition characterized by inadequate
      blood flow to the bowel resulting from stenosis of one or more of the three
      mesenteric arteries. Fibromuscular dysplasia is the most common cause in children
      and young adults; whereas atherosclerosis is the most common cause in the
      elderly. Treatment is mandatory in symptomatic patients, because it may lead to
      malnutrition, bowel infarction or even death.Herein, we present the case of a 14
      year old male, diagnosed with CMI who underwent percutaneous balloon angioplasty
      (PTA) followed by stent placement with immediate positive results. 

PMID- 25075284
TI  - Case Report: Detection and quantification of tumor cells in peripheral blood and
      ascitic fluid from a metastatic esophageal cancer patient using the CellSearch
      ((r)) technology.
AB  - Analysis of ascitic fluid should help to identify and characterize malignant
      cells in gastrointestinal cancer. However, despite a high specificity, the
      sensitivity of traditional ascitic fluid cytology remains insufficient, at around
      60%. Since 2004 the CellSearch ((r)) technology has shown its advantages in the
      detection of circulating tumor cells (CTCs) in peripheral blood, which can
      perform an accurate diagnosis and molecular analysis at the same time. To our
      knowledge, no previous study has explored the potential utility of this
      technology for the detection and quantification of tumor cells in ascitic fluid
      samples. Herein we report a case of metastatic esophageal adenocarcinoma in a 70
      year-old man presenting with dysphagia and a large amount of fluid in the
      peritoneal cavity. Analysis of a peripheral blood sample and ascites sample with
      the CellSearch ((r)) technology both revealed the presence of putative tumor
      cells that were positive for epithelial cell adhesion molecule (EpCAM) and
      cytokeratin (CK) expression. This study confirmed the hematogenous dissemination
      of esophageal cancer by the detection of circulating tumor cells in the
      peripheral blood, and is the first to demonstrate that tumor cells can be
      identified in ascitic fluid by using CellSearch ((r)) technology. 

PMID- 25075285
TI  - Lentigo maligna mimicking invasive melanoma in Mohs surgery: a case report.
AB  - Lentigo maligna is a lentiginous proliferation of atypical melanocytes confined
      to the epidermis, typically on chronically sun-damaged skin. Following biopsy and
      exclusion of invasive disease, therapy may involve Mohs surgery, topical
      treatment or radiotherapy. However, lentigo maligna often involves adnexal
      structures, creating histological difficulty in distinguishing these foci from
      invasive melanoma. We present a case in which, during Mohs excision, a nodule of
      severely atypical melanocytes appeared to lie within the dermis, potentially
      altering treatment and prognosis. The use of laminin-5 provided a means of
      resolving this diagnostic dilemma, facilitating continuation of Mohs surgery
      until tumour clearance was achieved. 

PMID- 25075286
TI  - Nominal Group Technique consultation of a Pulmonary Rehabilitation Programme.
AB  - OBJECTIVE: The purpose of the study was to determine what patients, professionals
      and significant others regarded as the most important positive- and challenging
      aspects of Pulmonary Rehabilitation Programmes for patients with Chronic
      Obstructive Pulmonary Disease (COPD) and to gain insight into how such programmes
      could be developed and improved. METHOD: A modified Nominal Group Technique
      method was used in three consultation workshops (one with COPD patients who had
      recently undertaken a Pulmonary Rehabilitation Programme; one with 'significant
      others' of the same patients; one with secondary care professionals who deliver
      the Pulmonary Rehabilitation Programme). RESULTS: Each of three workshops
      resulted in the production of approximately ten positive- and ten challenging
      aspects related to Pulmonary Rehabilitation Programmes.  These were further
      developed by a process of thematisation into seven broad themes.  The most
      important was ' the patient', followed by ' physical health'; jointly ranked as
      third were: ' mental health' and ' knowledge and education'.  ' The programme'
      and ' professional characteristics' were jointly ranked as fifth, with ' the
      future' being ranked as the least important theme. CONCLUSIONS: The modified
      Nominal Group Technique method allowed the development of a ranked thematic list
      that illustrated the important positive- and challenging aspects of Pulmonary
      Rehabilitation Programmes for patients with COPD. These themes should be core to
      planning future Pulmonary Rehabilitation Programmes, particularly if patients and
      carer views are to be considered.

PMID- 25075287
TI  - PsicquicGraph, a BioJS component to visualize molecular interactions from
      PSICQUIC servers.
AB  - SUMMARY: Protein interaction networks have become an essential tool in large
      scale data analysis, integration, and the visualization of high-throughput data
      in the context of complex cellular networks. Many individual databases are
      available that provide information on binary interactions of proteins and small
      molecules. Community efforts such as PSICQUIC aim to unify and standardize
      information emanating from these public databases. Here we introduce
      PsicquicGraph, an open-source, web-based visualization component for molecular
      interactions from PSIQUIC services. AVAILABILITY: PsicquicGraph is freely
      available at the BioJS Registry for download and enhancement. Instructions on how
      to use the tool are available here http://goo.gl/kDaIgZ and the source code can
      be found at http://github.com/biojs/biojs and DOI: 10.5281/zenodo.7709.

PMID- 25075288
TI  - PPI layouts: BioJS components for the display of Protein-Protein Interactions.
AB  - SUMMARY: We present two web-based components for the display of Protein-Protein
      Interaction networks using different self-organizing layout methods: force
      directed and circular. These components conform to the BioJS standard and can be
      rendered in an HTML5-compliant browser without the need for third-party plugins.
      We provide examples of interaction networks and how the components can be used to
      visualize them, and refer to a more complex tool that uses these components.
      AVAILABILITY: http://github.com/biojs/biojs;
      http://dx.doi.org/10.5281/zenodo.7753.

PMID- 25075289
TI  - Sequence, a BioJS component for visualising sequences.
AB  - SUMMARY: Sequences are probably the most common piece of information in sites
      providing biological data resources, particularly those related to genes and
      proteins. Multiple visual representations of the same sequence can be found
      across those sites. This can lead to an inconsistency compromising both the user
      experience and usability while working with graphical representations of a
      sequence. Furthermore, the code of the visualisation module is commonly embedded
      and merged with the rest of the application, making it difficult to reuse it in
      other applications. In this paper, we present a BioJS component for visualising
      sequences with a set of options supporting a flexible configuration of the visual
      representation, such as formats, colours, annotations, and columns, among others.
      This component aims to facilitate a common representation across different sites,
      making it easier for end users to move from one site to another. AVAILABILITY:
      http://www.ebi.ac.uk/Tools/biojs; http://dx.doi.org/10.5281/zenodo.8299.

PMID- 25075290
TI  - BioJS: an open source standard for biological visualisation - its status in 2014.
AB  - BioJS is a community-based standard and repository of functional components to
      represent biological information on the web. The development of BioJS has been
      prompted by the growing need for bioinformatics visualisation tools to be easily
      shared, reused and discovered. Its modular architecture makes it easy for users
      to find a specific functionality without needing to know how it has been built,
      while components can be extended or created for implementing new functionality.
      The BioJS community of developers currently provides a range of functionality
      that is open access and freely available. A registry has been set up that
      categorises and provides installation instructions and testing facilities at
      http://www.ebi.ac.uk/tools/biojs/. The source code for all components is
      available for ready use at https://github.com/biojs/biojs. 

PMID- 25075291
TI  - First regional evaluation of nuclear genetic diversity and population structure
      in northeastern coyotes ( Canis latrans).
AB  - Previous genetic studies of eastern coyotes ( Canis latrans) are based on one of
      two strategies: sampling many individuals using one or very few molecular
      markers, or sampling very few individuals using many genomic markers. Thus, a
      regional analysis of genetic diversity and population structure in eastern
      coyotes using many samples and several molecular markers is lacking. I evaluated
      genetic diversity and population structure in 385 northeastern coyotes using 16
      common single nucleotide polymorphisms (SNPs). A region-wide analysis of
      population structure revealed three primary genetic populations, but these do not
      correspond to the same three subdivisions inferred in a previous analysis of
      mitochondrial DNA sequences. More focused geographic analyses of population
      structure indicated that ample genetic structure occurs in coyotes from an
      intermediate contact zone where two range expansion fronts meet. These results
      demonstrate that genotyping several highly heterozygous SNPs in a large,
      geographically dense sample is an effective way to detect cryptic population
      genetic structure. The importance of SNPs in studies of population and wildlife
      genomics is rapidly increasing; this study adds to the growing body of recent
      literature that demonstrates the utility of SNPs ascertained from a model
      organism for evolutionary inference in closely related species. 

PMID- 25075292
TI  - Evidence from molecular dynamics simulations of conformational preorganization in
      the ribonuclease H active site.
AB  - Ribonuclease H1 (RNase H) enzymes are well-conserved endonucleases that are
      present in all domains of life and are particularly important in the life cycle
      of retroviruses as domains within reverse transcriptase. Despite extensive study,
      especially of the E. coli homolog, the interaction of the highly negatively
      charged active site with catalytically required magnesium ions remains poorly
      understood. In this work, we describe molecular dynamics simulations of the E.
      coli homolog in complex with magnesium ions, as well as simulations of other
      homologs in their apo states. Collectively, these results suggest that the active
      site is highly rigid in the apo state of all homologs studied and is
      conformationally preorganized to favor the binding of a magnesium ion. Notably,
      representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit
      similar active-site rigidity, suggesting that this dynamic feature is only subtly
      modulated by amino acid sequence and is primarily imposed by the distinctive
      RNase H protein fold. 

PMID- 25075293
TI  - A case of hypertrophic lupus erythematosus with negative CD123 staining and
      transepidermal elimination of elastin.
AB  - We report the case of a 49-year-old male with clinical and histological findings
      consistent with hypertrophic lupus erythematosus (HLE). HLE must be clinically
      and histologically differentiated from keratoacanthoma, hypertrophic lichen
      planus, squamous cell carcinoma and plaque type psoriasis. CD123 positivity and
      transepidermal elimination of elastin have recently been reported as tools to
      distinguish HLE. Interestingly, in this case, biopsies of two separate lesions
      failed to reveal these two features. The etiology of this discrepancy is unknown
      and further studies are needed to clarify the utility of CD123 positivity and
      transepidermal elimination of elastin in the diagnosis of hypertrophic lupus
      erythematosus. 

PMID- 25075294
TI  - Prevalence of primary outcome changes in clinical trials registered on
      ClinicalTrials.gov: a cross-sectional study.
AB  - BACKGROUND: An important principle in the good conduct of clinical trials is that
      a summary of the trial protocol, with a pre-defined primary outcome, should be
      freely available before the study commences. The clinical trials registry
      ClinicalTrials.gov provides one method of doing this, and once the trial is
      registered, any changes made to the primary outcome are documented. The
      objectives of this study were: to assess the proportion of registered trials on
      ClinicalTrials.gov that had the primary outcome changed; to assess when the
      primary outcome was changed in relation to the listed study start and end dates
      and to assess whether the primary outcome change had any relation to the study
      sponsor. METHODS: A cross-sectional analysis of all interventional clinical
      trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The
      main outcome was any change made to the initially listed primary outcome and the
      time of the change in relation to the trial start and end date. FINDINGS: Our
      analysis showed that 28229 of 89204 (31.7%) registered studies had their primary
      outcome changed.  Industry funding was associated with all primary outcome
      changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001;
      with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42,
      p<0.001; with primary outcome changes after primary completion date OR=1.84, 95%
      CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion
      date OR=1.82, 95% CI=1.73-1.91, p<0.001.  Conclusions A significant proportion of
      interventional trials registered on ClinicalTrials.gov have their primary
      outcomes altered after the listed study start and completion dates. These changes
      are associated with funding source.

PMID- 25075295
TI  - The reproductive season of scleractinian corals in Socotra, Yemen.
AB  - Determining when corals reproduce has clear management and economic implications.
      Here we document the reproductive condition of corals in the genus Acropora on
      the island of Socotra in Yemen during February 2014. Twenty percent of colonies
      (n = 143) contained mature gametes and 28% had immature gametes indicating that
      spawning will occur in both February and March in 2014, confirming previous
      anecdotal reports of coral spawning at this time in Socotra. Acropora typically
      reproduce in synchrony with many other broadcast spawning scleractinian corals,
      and we therefore predict that many other species are reproductively active at
      this time of year. 

PMID- 25075296
TI  - Severe form of hemolytic-uremic syndrome with multiple organ failure in a child:
      a case report.
AB  - INTRODUCTION: Hemolytic-uremic syndrome (HUS) is a leading cause of acute renal
      failure in infants and young children. It is traditionally defined as a triad of
      acute renal failure, hemolytic anemia and thrombocytopenia that occur within a
      week after prodromal hemorrhagic enterocolitis. Severe cases can also be
      presented by acute respiratory distress syndrome (ARDS), toxic megacolon with
      ileus, pancreatitis, central nervous system (CNS) disorders and multiple organ
      failure (MOF). CASE PRESENTATION: A previously healthy 4-year old Caucasian girl
      developed acute renal failure, thrombocytopenia and hemolytic anemia following a
      short episode of abdominal pain and bloody diarrhea. In the next week of, what
      initially appeared as typical HUS, she developed MOF, including ileus,
      pancreatitis, hepatitis, coma and ARDS, accompanied by hemodynamic instability
      and extreme leukocytosis. Nonetheless, the girl made a complete recovery after
      one month of the disease. She was successfully treated in the intensive care unit
      and significant improvement was noticed after plasmapheresis and continuous veno
      venous hemodialysis. CONCLUSIONS: Early start of plasmapheresis and meticulous
      supportive treatment in the intensive care unit, including renal placement
      therapy, may be the therapy of choice in severe cases of HUS presented by MOF.
      Monitoring of prognostic factors is important for early performance of
      appropriate diagnostic and therapeutical interventions.

PMID- 25075297
TI  - Trace amines inhibit insect odorant receptor function through antagonism of the
      co-receptor subunit.
AB  - Many insect behaviors are driven by olfaction, making insect olfactory receptors
      (ORs) appealing targets for insect control.  Insect ORs are odorant-gated ion
      channels, with each receptor thought to be composed of a representative from a
      large, variable family of odorant binding subunits and a highly conserved co
      receptor subunit (Orco), assembled in an unknown stoichiometry.  Synthetic Orco
      directed agonists and antagonists have recently been identified.  Several Orco
      antagonists have been shown to act via an allosteric mechanism to inhibit OR
      activation by odorants.  The high degree of conservation of Orco across insect
      species results in Orco antagonists having broad activity at ORs from a variety
      of insect species and suggests that the binding site for Orco ligands may serve
      as a modulatory site for compounds endogenous to insects or may be a target of
      exogenous compounds, such as those produced by plants.  To test this idea, we
      screened a series of biogenic and trace amines, identifying several as Orco
      antagonists.  Of particular interest were tryptamine, a plant-produced amine, and
      tyramine, an amine endogenous to the insect nervous system.  Tryptamine was found
      to be a potent antagonist of Orco, able to block Orco activation by an Orco
      agonist and to allosterically inhibit activation of ORs by odorants.  Tyramine
      had effects similar to those of tryptamine, but was less potent.  Importantly,
      both tryptamine and tyramine displayed broad activity, inhibiting odorant
      activation of ORs of species from three different insect orders (Diptera,
      Lepidoptera and Coleoptera), as well as odorant activation of six diverse ORs
      from a single species (the human malaria vector mosquito, Anopheles gambiae). 
      Our results suggest that endogenous and exogenous natural compounds serve as Orco
      ligands modulating insect olfaction and that Orco can be an important target for
      the development of novel insect repellants. 

PMID- 25075299
TI  - Chewing through the Miocene: an examination of the feeding musculature in the
      ground sloth Hapalops from South America (Mammalia: Pilosa).
AB  - Hapalops, a smaller-sized and early sloth of the Megatheroidea, appeared in the
      middle Miocene Santa Cruz formation of Argentina. This genus is part of the group
      from which later, larger megatheroids arose, i.e., Nothrotheriops and
      Megatherium. Many cranial characters support this idea; however Hapalops is not
      merely a smaller antecedent of the later forms. Specifically, Hapalops retains
      short anterior caniniform teeth, and a temporomandibular joint elevated above the
      cheek tooth row; a combination distinct among sloths. An elevated
      temporomandibular joint occurs in Bradypus, a tree sloth with anterior chisel
      shaped teeth instead of caniniforms, and the tree sloth Choloepus, which is
      aligned with the megalonychids, has anterior caniniforms. Hapalops has an
      elongated zygomatic ascending process that is reminiscent of that in Bradypus;
      however, the Bradypus skull is extremely foreshortened while that of Hapalops is
      elongated, as in nothrotheres, but not deepened as in megatheres. Previous work
      identified many sloth cranial character complexes, and functional limitations on
      skull feature combinations. The unique Hapalops character patterns indicate a
      selective feeder with a mediolaterally oriented grinding stroke during
      mastication. 

PMID- 25075298
TI  - Early elevated serum gamma glutamyl transpeptidase after liver transplantation is
      associated with better survival.
AB  - BACKGROUND: Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that
      plays a key role in the synthesis of the antioxidant glutathione. Epidemiological
      studies have linked high GGT with an increased risk of morbidity and
      cardiovascular mortality. In contrast, GGT is usually elevated in liver
      transplant recipients that experience good outcomes. AIMS: To study if and how
      GGT is correlated with mortality following liver transplantation. METHODS: We
      analyzed the prognostic relevance of serum GGT levels during the early and late
      postoperative period after liver transplantation in 522 consecutive adults. We
      also studied alanine aminotransferase, aspartate aminotransferase, and total
      bilirubin levels. RESULTS: Early after transplantation, the peak median
      (interquartile range) GGT levels were significantly higher in patients who
      survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84
      239) U/l, p<0.0001. In contrast, late after transplantation, GGT levels were
      significantly lower in patients who survived more than 5 years than those who did
      not ( p<0.01). The pattern of GGT levels also differed from those of alanine
      aminotransferase, aspartate aminotransferase, and total bilirubin early after
      transplantation, while these patterns were congruent late after transplantation.
      Kaplan-Meier survival analysis showed that early after transplantation the higher
      the GGT levels, the better the 90-day survival ( p<0.001). In contrast, late
      after transplantation, higher GGT levels were associated with a lower 5-year
      survival ( p<0.001). CONCLUSIONS:   These paradoxical findings may be explained
      by the time-dependent role of GGT in glutathione metabolism. Immediate
      postoperative elevation of GGT may indicate a physiological systemic response
      while chronic elevation reflects a pathological response.

PMID- 25075301
TI  - Data publication consensus and controversies.
AB  - The movement to bring datasets into the scholarly record as first class research
      products (validated, preserved, cited, and credited) has been inching forward for
      some time, but now the pace is quickening. As data publication venues
      proliferate, significant debate continues over formats, processes, and
      terminology. Here, we present an overview of data publication initiatives
      underway and the current conversation, highlighting points of consensus and
      issues still in contention. Data publication implementations differ in a variety
      of factors, including the kind of documentation, the location of the
      documentation relative to the data, and how the data is validated. Publishers may
      present the data as supplemental material to a journal article, with a
      descriptive "data paper," or independently. Complicating the situation, different
      initiatives and communities use the same terms to refer distinct but overlapping
      concepts. For instance, the term "published" means that the data is publicly
      available and citable to virtually everyone, but it may or may not imply that the
      data has been peer-reviewed. In turn, what is meant by data peer review is far
      from defined; standards and processes encompass the full range employed in
      reviewing the literature, plus some novel variations. Basic data citation is a
      point of consensus, but the general agreement on the core elements of a dataset
      citation frays if the data is dynamic or part of a larger set. Even as data
      publication is being defined, some are looking past publication to other
      metaphors, notably "data as software," for solutions to the more stubborn
      problems. 

PMID- 25075300
TI  - Toxoplasma gondii infection enhances the kairomonal valence of rat urine.
AB  - Many animals use chemicals as pheromones to communicate between individuals of
      the same species, for example to influence mate choice or to assert dominance.
      Pheromonal communication is an open broadcast system that can be intercepted by
      unintended receivers such as predators and prey. We have recently reported that
      male rats infected by the protozoan parasite Toxoplasma gondii become more
      attractive to female rats. This suggests a facilitatory effect of infection on
      rat pheromone production. In view of the open nature of pheromonal communication,
      we postulate that Toxoplasma gondii infection collateraly enhances kairomonal
      valence of infected rats to their prey. We compared the strength of kairomonal
      interception by mice when using scent marks from rats infected with Toxoplasma
      gondii vs. marks from uninfected control rats. Mice exhibited greater avoidance
      to both fresh urine and aged rat urine marks obtained from infected animals.
      These results indicate that, at least in some cases, parasitism can result in
      opportunity costs for hosts by making prey species more averse to them. 

PMID- 25075302
TI  - Neurosharing: large-scale data sets (spike, LFP) recorded from the hippocampal
      entorhinal system in behaving rats.
AB  - Using silicon-based recording electrodes, we recorded neuronal activity of the
      dorsal hippocampus and dorsomedial entorhinal cortex from behaving rats. The
      entorhinal neurons were classified as principal neurons and interneurons based on
      monosynaptic interactions and wave-shapes. The hippocampal neurons were
      classified as principal neurons and interneurons based on monosynaptic
      interactions, wave-shapes and burstiness. The data set contains recordings from
      7,736 neurons (6,100 classified as principal neurons, 1,132 as interneurons, and
      504 cells that did not clearly fit into either category) obtained during 442
      recording sessions from 11 rats (a total of 204.5 hours) while they were engaged
      in one of eight different behaviours/tasks. Both original and processed data
      (time stamp of spikes, spike waveforms, result of spike sorting and local field
      potential) are included, along with metadata of behavioural markers. Community
      driven data sharing may offer cross-validation of findings, refinement of
      interpretations and facilitate discoveries. 

PMID- 25075303
TI  - Transient acid treatment cannot induce neonatal somatic cells to become
      pluripotent stem cells.
AB  - Currently, there are genetic- and chemical-based methods for producing
      pluripotent stem cells from somatic cells, but all of them are extremely
      inefficient.  However, a simple and efficient technique has recently been
      reported by Obokata et al (2014a, b) that creates pluripotent stem cells through
      acid-based treatment of somatic cells.  These cells were named stimulus-triggered
      acquisition of pluripotency (STAP) stem cells. This would be a major game changer
      in regenerative medicine if the results could be independently replicated. Hence,
      we isolated CD45 (+) splenocytes from five-day-old Oct4-GFP mice and treated the
      cells with acidified (pH 5.7) Hank's Balanced Salt Solution (HBSS) for 25 min,
      using the methods described by Obokata et al 2014c. However, we found that this
      method did not induce the splenocytes to express the stem cell marker Oct4-GFP
      when observed under a confocal microscope three to six days after acid treatment.
      qPCR analysis also confirmed that acid treatment did not induce the splenocytes
      to express the stemness markers Oct4, Sox2 and Nanog.  In addition, we obtained
      similar results from acid-treated Oct4-GFP lung fibroblasts. In summary, we have
      not been able to produce STAP stem cells from neonatal splenocytes or lung
      fibroblasts using the acid-based treatment reported by Obokata et al (2014a, b,
      c). 

PMID- 25075304
TI  - Yeast Augmented Network Analysis (YANA): a new systems approach to identify
      therapeutic targets for human genetic diseases.
AB  - Genetic interaction networks that underlie most human diseases are highly complex
      and poorly defined. Better-defined networks will allow identification of a
      greater number of therapeutic targets. Here we introduce our Yeast Augmented
      Network Analysis (YANA) approach and test it with the X-linked spinal muscular
      atrophy (SMA) disease gene UBA1. First, we express UBA1 and a mutant variant in
      fission yeast and use high-throughput methods to identify fission yeast genetic
      modifiers of UBA1. Second, we analyze available protein-protein interaction
      network databases in both fission yeast and human to construct UBA1 genetic
      networks. Third, from these networks we identified potential therapeutic targets
      for SMA. Finally, we validate one of these targets in a vertebrate (zebrafish)
      SMA model. This study demonstrates the power of combining synthetic and chemical
      genetics with a simple model system to identify human disease gene networks that
      can be exploited for treating human diseases. 

PMID- 25075305
TI  - Ecological implications of reduced pollen deposition in alpine plants: a case
      study using a dominant cushion plant species.
AB  - The reproductive assurance hypothesis states that self-incompatible female plants
      must produce twice the number of seeds relative to their self-compatible
      hermaphroditic counterparts to persist in gynodioecious populations. This is a
      viable life-history strategy, provided that pollination rates are sufficiently
      high. However, reduced pollination rates in alpine plants are likely due to
      climate induced plant-pollinator mismatches and general declines in pollinators.
      Using a gynodioecious population of the dominant plant Silene acaulis
      (Caryophyllaceae), we tested the reproductive assurance hypothesis and also the
      stress gradient hypothesis with a series of pollinator exclusion trials and
      extensive measurements of subsequent reproductive output (gender ratio, plant
      size, percent fruit-set, fruit weight, seeds per fruit, total seeds, seed weight,
      and seed germination). The reproductive assurance hypothesis was supported with
      female plants being more sensitive to and less likely to be viable under
      reductions in pollination rates. These findings are the first to show that the
      stress gradient hypothesis is also supported under a gradient of pollen supply
      instead of environmental limitations. Beneficiary abundance was negatively
      correlated to percent fruit-set under current pollen supply, but became positive
      under reduced pollen supply suggesting that there are important plant-plant
      pollinator interactions related to reproduction in these alpine plant species. 

PMID- 25075306
TI  - Enrichment Map - a Cytoscape app to visualize and explore OMICs pathway
      enrichment results.
AB  - High-throughput OMICs experiments generate signals for millions of entities (i.e.
      genes, proteins, metabolites or any measurable biological entity) in the cell. In
      an effort to summarize and explore these signals, expression results are examined
      in the context of known pathways and processes, through enrichment analysis to
      generate a set of pathways and processes that is significantly enriched. Due to
      the high redundancy in annotation resources this often results in hundreds of
      sets. To facilitate the analysis of these results, we have developed the
      Enrichment Map app to visualize enrichments as a network. We have updated
      Enrichment Map to support Cytoscape 3, and have added additional features
      including new data formats and command line access. 

PMID- 25075307
TI  - Porting and using PanGIA for Cytoscape 3: challenges and solutions.
AB  - Much of the biologically significant functionality in Cytoscape is contained
      within third-party add-ons, called plugins in Cytoscape 2 and apps in Cytoscape
      3. In the transition from Cytoscape 2 to Cystoscape 3, some of the underlying
      assumptions upon which plugins relied changed, requiring a significant porting
      effort for plugins to work as Cytoscape 3 apps. PanGIA is a Cytoscape add-on
      (http://apps.cytoscape.org/apps/pangia) designed to analyze and visualize genetic
      interaction data in light of physical interaction data. In order to convert the
      PanGIA plugin to an app, various challenges, including those related to a
      transformed data model, concurrency, and randomization had to be overcome. In the
      process, the ability to control randomization was added to the GUI, a feature
      which was not only integral to the porting process, but which also ensures more
      easily reproducible scientific analysis for PanGIA users. Most authors of
      Cytoscape 2 plugins will face similar challenges porting their software to work
      with Cytoscape 3, and this paper gives details of how the PanGIA port addressed
      them. 

PMID- 25075309
TI  - Circumventing qPCR inhibition to amplify miRNAs in plasma.
AB  - BACKGROUND: Circulating microRNAs (c-miRNAs) have be identified in saliva, urine
      and blood, which has led to increasing interest in their development as
      biomarkers for diverse diseases including cancers. One of the key advantages of c
      miRNAs over other biomarkers is the ability to be amplified and quantified by
      quantitative PCR (qPCR). However, at phlebotomy when whole blood is dispensed
      into heparinized tubes, residual levels of the anti-coagulant lithium heparin may
      remain in the plasma and hence with RNA isolated from the plasma. This can
      confound the detection of c-miRNAs by qPCR because it inhibits reverse
      transcriptase (RT). Here we present a procedure, modified from earlier
      techniques, to detect c-miRNAs in plasma that improves sensitivity and
      streamlines performance. FINDINGS: Treatment of total RNA isolated from human
      blood plasma with Bacteroides heparinase I during reverse transcription at 37
      degrees C for one hour improved sensitivity and performance of the qPCR. This is
      in comparison to no treatment or treatment of the RNA prior to RT, which is the
      current suggested method and exposes plasma to Flavobacterium heparinum
      heparinase I for up to 2 hours before RT. This modest alteration improved qPCR
      performance and resulted in lowered threshold cycles (Ct) for detection of the
      target sequence, candidate c-miRNA biomarkers, and controls. It also reduced the
      expense and number of processing steps, shortening the duration of the assay and
      minimizing exposure of RNA to elevated temperatures. CONCLUSION: Incorporating
      Bacteroides heparinase I treatment into conventional RT protocols targeting c
      miRNA in plasma can be expected to expedite the discovery of biomarkers.

PMID- 25075308
TI  - Catheter associated urinary tract infections.
AB  - Urinary tract infection attributed to the use of an indwelling urinary catheter
      is one of the most common infections acquired by patients in health care
      facilities. As biofilm ultimately develops on all of these devices, the major
      determinant for development of bacteriuria is duration of catheterization. While
      the proportion of bacteriuric subjects who develop symptomatic infection is low,
      the high frequency of use of indwelling urinary catheters means there is a
      substantial burden attributable to these infections. Catheter-acquired urinary
      infection is the source for about 20% of episodes of health-care acquired
      bacteremia in acute care facilities, and over 50% in long term care facilities.
      The most important interventions to prevent bacteriuria and infection are to
      limit indwelling catheter use and, when catheter use is necessary, to discontinue
      the catheter as soon as clinically feasible. Infection control programs in health
      care facilities must implement and monitor strategies to limit catheter-acquired
      urinary infection, including surveillance of catheter use, appropriateness of
      catheter indications, and complications. Ultimately, prevention of these
      infections will require technical advances in catheter materials which prevent
      biofilm formation. 

PMID- 25075310
TI  - The validity of the non-exercise activity thermogenesis questionnaire evaluated
      by objectively measured daily physical activity by the triaxial accelerometer.
AB  - BACKGROUND: Physical inactivity is a major cardiovascular risk factor. Recently,
      we showed that non-exercise activity thermogenesis (NEAT) assessed by the self
      reported questionnaire is favorably associated with metabolic risks in patients
      with type 2 diabetes. The purpose of the present study was to examine the
      validity of the questionnaire by comparing with objectively measured daily
      physical activity (PA) by using the triaxial accelerometer. METHODS: Daily
      physical activity level (PAL) of 51 participants (24 men and 27 women) with type
      2 diabetes was measured by the triaxial accelerometer. At the same time, we
      evaluated their NEAT score using our original questionnaire modified from a
      compendium of physical activities. RESULTS: The NEAT score was significantly and
      positively correlated with PAL measured by the triaxial accelerometer (r = 0.604,
      P < 0.001). PAL was also significantly and positively correlated with both the
      locomotive NEAT score and the non-locomotive NEAT score (r = 0.444, P = 0.001 and
      r = 0.526, P < 0.001, respectively). CONCLUSIONS: The NEAT score measured by the
      self-reported questionnaire was highly correlated with PAL measured by the
      triaxial accelerometer. Our original NEAT questionnaire may be useful for
      evaluation of daily PAL in clinical practices.

PMID- 25075312
TI  - 100 years of crystallography: the IUCr launches a comprehensive open-access
      journal, IUCrJ.
AB  - IUCrJ is a fully open-access journal that aims to publish high-quality structural
      science papers. It has been launched for the International Year of
      Crystallography (IYCr2014). 

PMID- 25075313
TI  - Phasing tiny crystals.
AB  - For tiny crystals, their diffraction intensities at and between the Bragg peaks
      become measurable due to the limited number of the unit cells, which can in
      principle be used to directly phase the crystal structures. 

PMID- 25075311
TI  - Can supplementation with vitamin C and E alter physiological adaptations to
      strength training?
AB  - BACKGROUND: Antioxidant supplementation has recently been demonstrated to be a
      double-edged sword, because small to moderate doses of exogenous antioxidants are
      essential or beneficial, while high doses may have adverse effects. The adverse
      effects can be manifested in attenuated effects of exercise and training, as the
      antioxidants may shut down some redox-sensitive signaling in the exercised muscle
      fibers. However, conditions such as age may potentially modulate the need for
      antioxidant intake. Therefore, this paper describes experiments for testing the
      hypothesis that high dosages of vitamin C (1000 mg/day) and E (235 mg/day) have
      negative effects on adaptation to resistance exercise and training in young
      volunteers, but positive effects in older men. METHODS/DESIGN: We recruited a
      total of 73 volunteers. The participants were randomly assigned to receiving
      either vitamin C and E supplementation or a placebo. The study design was double
      blinded, and the participants followed an intensive training program for 10-12
      weeks. Tests and measurements aimed at assessing changes in physical performance
      (maximal strength) and physiological characteristics (muscle mass), as well as
      biochemical and cellular systems and structures (e.g., cell signaling and
      morphology). DISCUSSION: Dietary supplements, such as vitamin C and E, are used
      by many people, especially athletes. The users often believe that high dosages of
      supplements improve health (resistance to illness and disease) and physical
      performance. These assumptions are, however, generally not supported in the
      scientific literature. On the contrary, some studies have indicated that high
      dosages of antioxidant supplements have negative effects on exercise-induced
      adaptation processes. Since this issue concerns many people and few randomized
      controlled trials have been conducted in humans, further studies are highly
      warranted. TRIAL REGISTRATION: ACTRN12614000065695.

PMID- 25075314
TI  - Type II halogen...halogen contacts are halogen bonds.
AB  - Cl/Br/I alternative substitutions in a series of dihalophenols indicate that type
      I and type II halogen...halogen contacts have different chemical nature. Only the
      latter ones qualify as true halogen bonds, according to the recent IUPAC
      definition. 

PMID- 25075315
TI  - Crystal landscape in the orcinol:4,4'-bipyridine system: synthon modularity,
      polymorphism and transferability of multipole charge density parameters.
AB  - Polymorphism in the orcinol:4,4'-bipyridine cocrystal system is analyzed in terms
      of a robust convergent modular phenol?pyridine supramolecular synthon. Employing
      the Synthon Based Fragments Approach (SBFA) to transfer the multipole charge
      density parameters, it is demonstrated that the crystal landscape can be
      quantified in terms of intermolecular interaction energies in the five crystal
      forms so far isolated in this complex system. There are five crystal forms. The
      first has an open, divergent O-H?N based structure with alternating orcinol and
      bipyridine molecules. The other four polymorphs have different three-dimensional
      packing but all of them are similar at an interaction level, and are based on a
      modular O-H?N mediated supramolecular synthon that consists of two orcinol and
      two bipyridine molecules in a closed, convergent structure. The SBFA method,
      which depends on the modularity of synthons, provides good agreement between
      experiment and theory because it takes into account the supramolecular
      contribution to charge density. The existence of five crystal forms in this
      system shows that polymorphism in cocrystals need not be considered to be an
      unusual phenomenon. Studies of the crystal landscape could lead to an
      understanding of the kinetic pathways that control the crystallization processes,
      in other words the valleys in the landscape. These pathways are traditionally not
      considered in exercises pertaining to computational crystal structure prediction,
      which rather monitors the thermodynamics of the various stable forms in the
      system, in other words the peaks in the landscape. 

PMID- 25075316
TI  - Ab-initio phasing using nanocrystal shape transforms with incomplete unit cells.
AB  - X-ray free electron lasers are used in measuring diffraction patterns from
      nanocrystals in the 'diffract-before-destroy' mode by outrunning radiation
      damage. The finite-sized nanocrystals provide an opportunity to recover intensity
      between Bragg spots by removing the modulating function that depends on crystal
      shape, i.e. the transform of the crystal shape. This shape-transform dividing-out
      scheme for solving the phase problem has been tested using simulated examples
      with cubic crystals. It provides a phasing method which does not require atomic
      resolution data, chemical modification to the sample, or modelling based on the
      protein databases. It is common to find multiple structural units (e.g.
      molecules, in symmetry-related positions) within a single unit cell, therefore
      incomplete unit cells (e.g. one additional molecule) can be observed at surface
      layers of crystals. In this work, the effects of such incomplete unit cells on
      the 'dividing-out' phasing algorithm are investigated using 2D crystals within
      the projection approximation. It is found that the incomplete unit cells do not
      hinder the recovery of the scattering pattern from a single unit cell (after
      dividing out the shape transforms from data merged from many nanocrystals of
      different sizes), assuming that certain unit-cell types are preferred. The
      results also suggest that the dynamic range of the data is a critical issue to be
      resolved in order to apply the shape transform method practically. 

PMID- 25075317
TI  - Structural insights into WcbI, a novel polysaccharide-biosynthesis enzyme.
AB  - Capsular polysaccharides (CPSs) are protective structures on the surfaces of many
      Gram-negative bacteria. The principal CPS of the human pathogen and Tier 1 select
      agent Burkholderia pseudomallei consists of a linear repeat of --3)--2-O-acetyl-6
      deoxy-beta-d-manno-heptopyranose-(1-. This CPS is critical to the virulence of
      this emerging pathogen and represents a key target for the development of novel
      therapeutics. wcbI is one of several genes in the CPS biosynthetic cluster whose
      deletion leads to significant attenuation of the pathogen; unlike most others, it
      has no homologues of known function and no detectable sequence similarity to any
      protein with an extant structure. Here, the crystal structure of WcbI bound to
      its proposed product, coenzyme A, is reported at 1.38 A resolution, solved using
      the halide-soak method with multiple anomalous dispersion. This structure reveals
      that WcbI incorporates a previously described 100-amino-acid subdomain into a
      novel, principally helical fold (310 amino acids). This fold adopts a cradle-like
      structure, with a deep binding pocket for CoA in the loop-rich cradle. Structural
      analysis and biophysical assays suggest that WcbI functions as an
      acetyltransferase enzyme, whilst biochemical tests suggest that another
      functional module might be required to assist its activity in forming the mature
      B. pseudomallei capsule. 

PMID- 25075318
TI  - Analysis of the structural continuity in twinned crystals in terms of pseudo
      eigensymmetry of crystallographic orbits.
AB  - The reticular theory of twinning gives the necessary conditions on the lattice
      level for the formation of twins. The latter are based on the continuation, more
      or less approximate, of a substructure through the composition surface. The
      analysis of this structural continuity can be performed in terms of the
      eigensymmetry of the crystallographic orbits corresponding to occupied Wyckoff
      positions in the structure. If [Formula: see text] is the space group of the
      individual and [Formula: see text] a space group which fixes the twin lattice
      obtained as an intersection of the space groups of the individuals in their
      respective orientations, then a structural continuity is obtained if (1) the
      eigensymmetry of an orbit under [Formula: see text] contains the twin operation;
      (2) the eigensymmetry of a union of orbits under [Formula: see text] contains the
      twin operation; (3) the eigensymmetry of a split orbit under [Formula: see text]
      contains the twin operation; or (4) the eigensymmetry of a union of split orbits
      under [Formula: see text] contains the twin operation. The case of the twins in
      melilite is analysed: the (approximate) restoration of some of the orbits
      explains the formation of these twins. 

PMID- 25075319
TI  - Halogen bonds in some dihalogenated phenols: applications to crystal engineering.
AB  - 3,4-Dichlorophenol (1) crystallizes in the tetragonal space group I41/a with a
      short axis of 3.7926 (9) A. The structure is unique in that both type I and type
      II Cl?Cl interactions are present, these contact types being distinguished by the
      angle ranges of the respective C-Cl?Cl angles. The present study shows that these
      two types of contacts are utterly different. The crystal structures of 4-bromo-3
      chlorophenol (2) and 3-bromo-4-chlorophenol (3) have been determined. The crystal
      structure of (2) is isomorphous to that of (1) with the Br atom in the 4-position
      participating in a type II interaction. However, the monoclinic P21/c packing of
      compound (3) is different; while the structure still has O-H?O hydrogen bonds,
      the tetramer O-H?O synthon seen in (1) and (2) is not seen. Rather than a type I
      Br?Br interaction which would have been mandated if (3) were isomorphous to (1)
      and (2), Br forms a Br?O contact wherein its electrophilic character is clearly
      evident. Crystal structures of the related compounds 4-chloro-3-iodophenol (4)
      and 3,5-dibromophenol (5) were also determined. A computational survey of the
      structural landscape was undertaken for (1), (2) and (3), using a crystal
      structure prediction protocol in space groups P21/c and I41/a with the COMPASS26
      force field. While both tetragonal and monoclinic structures are energetically
      reasonable for all compounds, the fact that (3) takes the latter structure
      indicates that Br prefers type II over type I contacts. In order to differentiate
      further between type I and type II halogen contacts, which being chemically
      distinct are expected to have different distance fall-off properties, a variable
      temperature crystallography study was performed on compounds (1), (2) and (4).
      Length variations with temperature are greater for type II contacts compared with
      type I. The type II Br?Br interaction in (2) is stronger than the corresponding
      type II Cl?Cl interaction in (1), leading to elastic bending of the former upon
      application of mechanical stress, which contrasts with the plastic deformation of
      (1). The observation of elastic deformation in (2) is noteworthy; in that it
      finds an explanation based on the strengths of the respective halogen bonds, it
      could also be taken as a good starting model for future property design. Cl/Br
      isostructurality is studied with the Cambridge Structural Database and it is
      indicated that this isostructurality is based on shape and size similarity of Cl
      and Br, rather than arising from any chemical resemblance. 

PMID- 25075320
TI  - On the correlation between hydrogen bonding and melting points in the inositols.
AB  - Inositol, 1,2,3,4,5,6-hexahydroxycyclohexane, exists in nine stereoisomers with
      different crystal structures and melting points. In a previous paper on the
      relationship between the melting points of the inositols and the hydrogen-bonding
      patterns in their crystal structures [Simperler et al. (2006 ?). CrystEngComm 8,
      589], it was noted that although all inositol crystal structures known at that
      time contained 12 hydrogen bonds per molecule, their melting points span a large
      range of about 170  degrees C. Our preliminary investigations suggested that the
      highest melting point must be corrected for the effect of molecular symmetry, and
      that the three lowest melting points may need to be revised. This prompted a full
      investigation, with additional experiments on six of the nine inositols. Thirteen
      new phases were discovered; for all of these their crystal structures were
      examined. The crystal structures of eight ordered phases could be determined, of
      which seven were obtained from laboratory X-ray powder diffraction data. Five
      additional phases turned out to be rotator phases and only their unit cells could
      be determined. Two previously unknown melting points were measured, as well as
      most enthalpies of melting. Several previously reported melting points were shown
      to be solid-to-solid phase transitions or decomposition points. Our experiments
      have revealed a complex picture of phases, rotator phases and phase transitions,
      in which a simple correlation between melting points and hydrogen-bonding
      patterns is not feasible. 

PMID- 25075321
TI  - Do we see what we should see? Describing non-covalent interactions in protein
      structures including precision.
AB  - The power of X-ray crystal structure analysis as a technique is to 'see where the
      atoms are'. The results are extensively used by a wide variety of research
      communities. However, this 'seeing where the atoms are' can give a false sense of
      security unless the precision of the placement of the atoms has been taken into
      account. Indeed, the presentation of bond distances and angles to a false
      precision (i.e. to too many decimal places) is commonplace. This article has
      three themes. Firstly, a basis for a proper representation of protein crystal
      structure results is detailed and demonstrated with respect to analyses of
      Protein Data Bank entries. The basis for establishing the precision of placement
      of each atom in a protein crystal structure is non-trivial. Secondly, a knowledge
      base harnessing such a descriptor of precision is presented. It is applied here
      to the case of salt bridges, i.e. ion pairs, in protein structures; this is the
      most fundamental place to start with such structure-precision representations
      since salt bridges are one of the tenets of protein structure stability. Ion
      pairs also play a central role in protein oligomerization, molecular recognition
      of ligands and substrates, allosteric regulation, domain motion and alpha-helix
      capping. A new knowledge base, SBPS (Salt Bridges in Protein Structures), takes
      these structural precisions into account and is the first of its kind. The third
      theme of the article is to indicate natural extensions of the need for such a
      description of precision, such as those involving metalloproteins and the
      determination of the protonation states of ionizable amino acids. Overall, it is
      also noted that this work and these examples are also relevant to protein three
      dimensional structure molecular graphics software. 

PMID- 25075322
TI  - New perspectives in biological crystallography.
AB  - Biological crystallography has never been more vibrant. Celebrating this, IUCrJ
      invites high-impact papers from across the whole spectrum of structural biology
      and medicine. 

PMID- 25075323
TI  - Serial crystallography using synchrotron radiation.
AB  - A brief history is given of how X-ray diffraction data from crystals have been
      recorded. Today there are new possibilities, spawned by the availability of free
      electron lasers that produce powerful femtosecond long X-ray pulses. 

PMID- 25075324
TI  - Serial crystallography on in vivo grown microcrystals using synchrotron
      radiation.
AB  - Crystal structure determinations of biological macromolecules are limited by the
      availability of sufficiently sized crystals and by the fact that crystal quality
      deteriorates during data collection owing to radiation damage. Exploiting a
      micrometre-sized X-ray beam, high-precision diffractometry and shutterless data
      acquisition with a pixel-array detector, a strategy for collecting data from many
      micrometre-sized crystals presented to an X-ray beam in a vitrified suspension is
      demonstrated. By combining diffraction data from 80 Trypanosoma brucei
      procathepsin B crystals with an average volume of 9 um(3), a complete data set to
      3.0 A resolution has been assembled. The data allowed the refinement of a
      structural model that is consistent with that previously obtained using free
      electron laser radiation, providing mutual validation. Further improvements of
      the serial synchrotron crystallography technique and its combination with serial
      femtosecond crystallography are discussed that may allow the determination of
      high-resolution structures of micrometre-sized crystals. 

PMID- 25075325
TI  - Femtosecond X-ray diffraction from two-dimensional protein crystals.
AB  - X-ray diffraction patterns from two-dimensional (2-D) protein crystals obtained
      using femtosecond X-ray pulses from an X-ray free-electron laser (XFEL) are
      presented. To date, it has not been possible to acquire transmission X-ray
      diffraction patterns from individual 2-D protein crystals due to radiation
      damage. However, the intense and ultrafast pulses generated by an XFEL permit a
      new method of collecting diffraction data before the sample is destroyed.
      Utilizing a diffract-before-destroy approach at the Linac Coherent Light Source,
      Bragg diffraction was acquired to better than 8.5 A resolution for two different
      2-D protein crystal samples each less than 10 nm thick and maintained at room
      temperature. These proof-of-principle results show promise for structural
      analysis of both soluble and membrane proteins arranged as 2-D crystals without
      requiring cryogenic conditions or the formation of three-dimensional crystals. 

PMID- 25075326
TI  - The structure of a purple acid phosphatase involved in plant growth and pathogen
      defence exhibits a novel immunoglobulin-like fold.
AB  - Phosphatases function in the production, transport and recycling of inorganic
      phosphorus, which is crucial for cellular metabolism and bioenergetics, as well
      as in bacterial killing, since they are able to generate reactive oxygen species
      via Fenton chemistry. Diphosphonucleotide phosphatase/phosphodiesterase (PPD1), a
      glycoprotein plant purple acid phosphatase (PAP) from yellow lupin seeds,
      contains a bimetallic Fe-Mn catalytic site which is most active at acidic pH.
      Unlike other plant PAPs, PPD1 cleaves the pyrophosphate bond in
      diphosphonucleotides and the phosphodiester bond in various phosphodiesters. The
      homohexameric organization of PPD1, as revealed by a 1.65 A resolution crystal
      structure and confirmed by solution X-ray scattering, is unique among plant PAPs,
      for which only homodimers have previously been reported. A phosphate anion is
      bound in a bidentate fashion at the active site, bridging the Fe and Mn atoms in
      a binding mode similar to that previously reported for sweet potato PAP, which
      suggests that common features occur in their catalytic mechanisms. The N-terminal
      domain of PPD1 has an unexpected and unique fibronectin type III-like fold that
      is absent in other plant PAPs. Here, the in vitro DNA-cleavage activity of PPD1
      is demonstrated and it is proposed that the fibronectin III-like domain, which
      'overhangs' the active site, is involved in DNA selectivity, binding and
      activation. The degradation of DNA by PPD1 implies a role for PPD1 in plant
      growth and repair and in pathogen defence. 

PMID- 25075327
TI  - Anharmonicity and isomorphic phase transition: a multi-temperature X-ray single
      crystal and powder diffraction study of 1-(2'-aminophenyl)-2-methyl-4
      nitroimidazole.
AB  - The harmonic model of atomic nuclear motions is usually enough for multipole
      modelling of high-resolution X-ray diffraction data; however, in some molecular
      crystals, such as 1-(2'-aminophenyl)-2-methyl-4-nitro-1H-imidazole [Paul,
      Kubicki, Jelsch et al. (2011 ?). Acta Cryst. B67, 365-378], it may not be
      sufficient for a correct description of the charge-density distribution.
      Multipole refinement using harmonic atom vibrations does not lead to the best
      electron density model in this case and the so-called 'shashlik-like' pattern of
      positive and negative residual electron density peaks is observed in the vicinity
      of some atoms. This slight disorder, which cannot be modelled by split atoms, was
      solved using third-order anharmonic nuclear motion (ANM) parameters. Multipole
      refinement of the experimental high-resolution X-ray diffraction data of 1-(2'
      aminophenyl)-2-methyl-4-nitro-1H-imidazole at three different temperatures (10,
      35 and 70 K) and a series of powder diffraction experiments (20 <= T <= 300 K)
      were performed to relate this anharmonicity observed for several light atoms (N
      atoms of amino and nitro groups, and O atoms of nitro groups) to an isomorphic
      phase transition reflected by a change in the b cell parameter around 65 K. The
      observed disorder may result from the coexistence of domains of two phases over a
      large temperature range, as shown by low-temperature powder diffraction. 

PMID- 25075328
TI  - The enrichment ratio of atomic contacts in crystals, an indicator derived from
      the Hirshfeld surface analysis.
AB  - The partitioning of space with Hirshfeld surfaces enables the analysis of
      fingerprint molecular interactions in crystalline environments. This study uses
      the decomposition of the crystal contact surface between pairs of interacting
      chemical species to derive an enrichment ratio. This quantity enables the
      analysis of the propensity of chemical species to form intermolecular
      interactions with themselves and other species. The enrichment ratio is obtained
      by comparing the actual contacts in the crystal with those computed as if all
      types of contacts had the same probability to form. The enrichments and contact
      tendencies were analyzed in several families of compounds, based on chemical
      composition and aromatic character. As expected, the polar contacts of the type
      H?N, H?O and H?S, which are generally hydrogen bonds, show enrichment values
      larger than unity. O?O and N?N contacts are impoverished while H?H interactions
      display enrichment ratios which are generally close to unity or slightly lower.
      In aromatic compounds, C?C contacts can display large enrichment ratios due to
      extensive pi?pi stacking in the crystal packings of heterocyclic compounds. C?C
      contacts are, however, less enriched in pure (C,H) hydrocarbons as pi?pi stacking
      is not so favourable from the electrostatic point of view compared with
      heterocycles. C?H contacts are favoured in (C,H) aromatics, but these
      interactions occur less in compounds containing O, N or S as some H atoms are
      then involved in hydrogen bonds. The study also highlights the fact that hydrogen
      is a prefered interaction partner for fluorine. 

PMID- 25075329
TI  - Structural insight into activity enhancement and inhibition of H64A carbonic
      anhydrase II by imidazoles.
AB  - Human carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the
      hydration and dehydration of CO2 and HCO3 (-), respectively. The reaction follows
      a ping-pong mechanism, in which the rate-limiting step is the transfer of a
      proton from the zinc-bound solvent (OH(-)/H2O) in/out of the active site via
      His64, which is widely believed to be the proton-shuttling residue. The decreased
      catalytic activity (~20-fold lower with respect to the wild type) of a variant of
      CA II in which His64 is replaced with Ala (H64A CA II) can be enhanced by
      exogenous proton donors/acceptors, usually derivatives of imidazoles and
      pyridines, to almost the wild-type level. X-ray crystal structures of H64A CA II
      in complex with four imidazole derivatives (imidazole, 1--methylimidazole, 2-
      methylimidazole and 4-methylimidazole) have been determined and reveal multiple
      binding sites. Two of these imidazole binding sites have been identified that
      mimic the positions of the 'in' and 'out' rotamers of His64 in wild-type CA II,
      while another directly inhibits catalysis by displacing the zinc-bound solvent.
      The data presented here not only corroborate the importance of the imidazole side
      chain of His64 in proton transfer during CA catalysis, but also provide a
      complete structural understanding of the mechanism by which imidazoles enhance
      (and inhibit when used at higher concentrations) the activity of H64A CA II. 

PMID- 25075330
TI  - Acemetacin cocrystals and salts: structure solution from powder X-ray data and
      form selection of the piperazine salt.
AB  - Acemetacin (ACM) is a non-steroidal anti-inflammatory drug (NSAID), which causes
      reduced gastric damage compared with indomethacin. However, acemetacin has a
      tendency to form a less soluble hydrate in the aqueous medium. We noted
      difficulties in the preparation of cocrystals and salts of acemetacin by
      mechanochemical methods, because this drug tends to form a hydrate during any
      kind of solution-based processing. With the objective to discover a solid form of
      acemetacin that is stable in the aqueous medium, binary adducts were prepared by
      the melt method to avoid hydration. The coformers/salt formers reported are
      pyridine carboxamides [nicotinamide (NAM), isonicotinamide (INA), and
      picolinamide (PAM)], caprolactam (CPR), p-aminobenzoic acid (PABA), and
      piperazine (PPZ). The structures of an ACM-INA cocrystal and a binary adduct ACM
      PABA were solved using single-crystal X-ray diffraction. Other ACM cocrystals,
      ACM-PAM and ACM-CPR, and the piperazine salt ACM-PPZ were solved from high
      resolution powder X-ray diffraction data. The ACM-INA cocrystal is sustained by
      the acid?pyridine heterosynthon and N-H?O catemer hydrogen bonds involving the
      amide group. The acid?amide heterosynthon is present in the ACM-PAM cocrystal,
      while ACM-CPR contains carboxamide dimers of caprolactam along with acid-carbonyl
      (ACM) hydrogen bonds. The cocrystals ACM-INA, ACM-PAM and ACM-CPR are three
      dimensional isostructural. The carboxyl?carboxyl synthon in ACM-PABA posed
      difficulty in assigning the position of the H atom, which may indicate proton
      disorder. In terms of stability, the salts were found to be relatively stable in
      pH 7 buffer medium over 24 h, but the cocrystals dissociated to give ACM hydrate
      during the same time period. The ACM-PPZ salt and ACM-nicotinamide cocrystal
      dissolve five times faster than the stable hydrate form, whereas the ACM-PABA
      adduct has 2.5 times faster dissolution rate. The pharmaceutically acceptable
      piperazine salt of acemetacin exhibits superior stability, faster dissolution
      rate and is able to overcome the hydration tendency of the reference drug. 

PMID- 25075331
TI  - X-ray lasers and crystallography.
AB  - The development of X-ray lasers and their applications in crystallography is
      described. In the birth of this new field, IUCrJ is ideally positioned to present
      this research to both specialists in crystallography, and to the wider audience
      in structural biology. 

PMID- 25075332
TI  - Hidden motion made known - rotational X-ray tracking reveals spinning colloids.
AB  - Rotational x-ray tracking (RXT) is demonstrated as a promising new tool for
      investigating previously unobservable motion in crystalline nanoscale colloids.
      Its potential utility is demonstrated by applying it to measurements of the local
      viscoelastic properties of a gel-colloid nanocomposite. 

PMID- 25075333
TI  - Evidence of electronic polarization of the As ion in the superconducting phase of
      F-doped LaFeAsO.
AB  - Understanding the nature of superconductivity in iron-based compounds is
      essential in the development of new strategies to increase T c. Using a charge
      density analysis based on synchrotron radiation X-ray powder diffraction data, we
      found that the charge carriers only accumulated in the iron layer of the
      superconducting phase of LaFeAsO1 - x F x at low temperatures. Analysis of the
      electrostatic potential distribution revealed the concerted enhancement of the
      electronic polarization of the As ions and the carrier redistribution. This
      suggests that the enhanced electronic polarization of the As ion plays an
      important role in inducing high T c superconductivity, and that the polaron
      concept, which has been previously regarded as an untenable mechanism, should be
      reconsidered for the description of the iron-arsenide superconducting phase. 

PMID- 25075334
TI  - Hierarchical dielectric orders in layered ferroelectrics Bi2SiO5.
AB  - Electric dipole engineering is now an emerging technology for high electron
      mobility transistors, ferroelectric random access memory and multiferroic devices
      etc. Although various studies to provide insight into dipole moment behaviour,
      such as phase transition, order and disorder states, have been reported,
      macroscopic spontaneous polarization has been mainly discussed so far. Here,
      visualization of the electric dipole arrangement in layered ferroelectrics
      Bi2SiO5 by means of combined analysis of maximum entropy charge density and
      electrostatic potential distribution analysis based on synchrotron radiation X
      ray powder diffraction data is reported. It was found that the hierarchical
      dipole orders, the weak-ferroelectric and ferroelectric configurations, were
      observed in the Bi2O2 and the SiO3 layers, respectively, and the ferrielectric
      configuration was realised by the interlayer interaction. This discovery provides
      a new method to visualize the local polarization in ferroelectric materials. 

PMID- 25075335
TI  - Evolution of atomic structure during nanoparticle formation.
AB  - Understanding the mechanism of nanoparticle formation during synthesis is a key
      prerequisite for the rational design and engineering of desirable materials
      properties, yet remains elusive due to the difficulty of studying structures at
      the nanoscale under real conditions. Here, the first comprehensive structural
      description of the formation of a nanoparticle, yttria-stabilized zirconia (YSZ),
      all the way from its ionic constituents in solution to the final crystal, is
      presented. The transformation is a complicated multi-step sequence of atomic
      reorganizations as the material follows the reaction pathway towards the
      equilibrium product. Prior to nanoparticle nucleation, reagents reorganize into
      polymeric species whose structure is incompatible with the final product. Instead
      of direct nucleation of clusters into the final product lattice, a highly
      disordered intermediate precipitate forms with a local bonding environment
      similar to the product yet lacking the correct topology. During maturation, bond
      reforming occurs by nucleation and growth of distinct domains within the
      amorphous intermediary. The present study moves beyond kinetic modeling by
      providing detailed real-time structural insight, and it is demonstrated that YSZ
      nanoparticle formation and growth is a more complex chemical process than
      accounted for in conventional models. This level of mechanistic understanding of
      the nanoparticle formation is the first step towards more rational control over
      nanoparticle synthesis through control of both solution precursors and reaction
      intermediaries. 

PMID- 25075336
TI  - Brownian motion studies of viscoelastic colloidal gels by rotational single
      particle tracking.
AB  - Colloidal gels have unique properties due to a complex microstructure which forms
      into an extended network. Although the bulk properties of colloidal gels have
      been studied, there has been difficulty correlating those properties with
      individual colloidal dynamics on the microscale due to the very high viscosity
      and elasticity of the material. We utilize rotational X-ray tracking (RXT) to
      investigate the rotational motion of component crystalline colloidal particles in
      a colloidal gel of alumina and decanoic acid. Our investigation has determined
      that the high elasticity of the bulk is echoed by a high elasticity experienced
      by individual colloidal particles themselves but also finds an unexpected high
      degree of rotational diffusion, indicating a large degree of freedom in the
      rotational motion of individual colloids even within a tightly bound system. 

PMID- 25075338
TI  - First spin-resolved electron distributions in crystals from combined polarized
      neutron and X-ray diffraction experiments.
AB  - Since the 1980s it has been possible to probe crystallized matter, thanks to X
      ray or neutron scattering techniques, to obtain an accurate charge density or
      spin distribution at the atomic scale. Despite the description of the same
      physical quantity (electron density) and tremendous development of sources,
      detectors, data treatment software etc., these different techniques evolved
      separately with one model per experiment. However, a breakthrough was recently
      made by the development of a common model in order to combine information coming
      from all these different experiments. Here we report the first experimental
      determination of spin-resolved electron density obtained by a combined treatment
      of X-ray, neutron and polarized neutron diffraction data. These experimental spin
      up and spin down densities compare very well with density functional theory (DFT)
      calculations and also confirm a theoretical prediction made in 1985 which claims
      that majority spin electrons should have a more contracted distribution around
      the nucleus than minority spin electrons. Topological analysis of the resulting
      experimental spin-resolved electron density is also briefly discussed. 

PMID- 25075337
TI  - Avoidable errors in deposited macromolecular structures: an impediment to
      efficient data mining.
AB  - Whereas the vast majority of the more than 85 000 crystal structures of
      macromolecules currently deposited in the Protein Data Bank are of high quality,
      some suffer from a variety of imperfections. Although this fact has been pointed
      out in the past, it is still worth periodic updates so that the metadata obtained
      by global analysis of the available crystal structures, as well as the
      utilization of the individual structures for tasks such as drug design, should be
      based on only the most reliable data. Here, selected abnormal deposited
      structures have been analysed based on the Bayesian reasoning that the
      correctness of a model must be judged against both the primary evidence as well
      as prior knowledge. These structures, as well as information gained from the
      corresponding publications (if available), have emphasized some of the most
      prevalent types of common problems. The errors are often perfect illustrations of
      the nature of human cognition, which is frequently influenced by preconceptions
      that may lead to fanciful results in the absence of proper validation. Common
      errors can be traced to negligence and a lack of rigorous verification of the
      models against electron density, creation of non-parsimonious models, generation
      of improbable numbers, application of incorrect symmetry, illogical presentation
      of the results, or violation of the rules of chemistry and physics. Paying more
      attention to such problems, not only in the final validation stages but during
      the structure-determination process as well, is necessary not only in order to
      maintain the highest possible quality of the structural repositories and
      databases but most of all to provide a solid basis for subsequent studies,
      including large-scale data-mining projects. For many scientists PDB deposition is
      a rather infrequent event, so the need for proper training and supervision is
      emphasized, as well as the need for constant alertness of reason and critical
      judgment as absolutely necessary safeguarding measures against such problems.
      Ways of identifying more problematic structures are suggested so that their users
      may be properly alerted to their possible shortcomings. 

PMID- 25075339
TI  - Crystallography, materials and computation.
AB  - The growing role of structural studies of materials and of computation in
      structural science is highlighted. 

PMID- 25075340
TI  - Multiple chemical scaffolds inhibit a promising Leishmania drug target.
AB  - The need for an effective oral therapy for leishmaniasis is addressed through the
      study of the target N-myristoyltransferase from Leishmania major. 

PMID- 25075341
TI  - Room-temperature macromolecular serial crystallography using synchrotron
      radiation.
AB  - A new approach for collecting data from many hundreds of thousands of
      microcrystals using X-ray pulses from a free-electron laser has recently been
      developed. Referred to as serial crystallography, diffraction patterns are
      recorded at a constant rate as a suspension of protein crystals flows across the
      path of an X-ray beam. Events that by chance contain single-crystal diffraction
      patterns are retained, then indexed and merged to form a three-dimensional set of
      reflection intensities for structure determination. This approach relies upon
      several innovations: an intense X-ray beam; a fast detector system; a means to
      rapidly flow a suspension of crystals across the X-ray beam; and the
      computational infrastructure to process the large volume of data. Originally
      conceived for radiation-damage-free measurements with ultrafast X-ray pulses, the
      same methods can be employed with synchrotron radiation. As in powder
      diffraction, the averaging of thousands of observations per Bragg peak may
      improve the ratio of signal to noise of low-dose exposures. Here, it is shown
      that this paradigm can be implemented for room-temperature data collection using
      synchrotron radiation and exposure times of less than 3 ms. Using lysozyme
      microcrystals as a model system, over 40 000 single-crystal diffraction patterns
      were obtained and merged to produce a structural model that could be refined to
      2.1 A resolution. The resulting electron density is in excellent agreement with
      that obtained using standard X-ray data collection techniques. With further
      improvements the method is well suited for even shorter exposures at future and
      upgraded synchrotron radiation facilities that may deliver beams with 1000 times
      higher brightness than they currently produce. 

PMID- 25075342
TI  - The PDB_REDO server for macromolecular structure model optimization.
AB  - The refinement and validation of a crystallographic structure model is the last
      step before the coordinates and the associated data are submitted to the Protein
      Data Bank (PDB). The success of the refinement procedure is typically assessed by
      validating the models against geometrical criteria and the diffraction data, and
      is an important step in ensuring the quality of the PDB public archive [Read et
      al. (2011 ?), Structure, 19, 1395-1412]. The PDB_REDO procedure aims for
      'constructive validation', aspiring to consistent and optimal refinement
      parameterization and pro-active model rebuilding, not only correcting errors but
      striving for optimal interpretation of the electron density. A web server for
      PDB_REDO has been implemented, allowing thorough, consistent and fully automated
      optimization of the refinement procedure in REFMAC and partial model rebuilding.
      The goal of the web server is to help practicing crystallo-graphers to improve
      their model prior to submission to the PDB. For this, additional steps were
      implemented in the PDB_REDO pipeline, both in the refinement procedure, e.g.
      testing of resolution limits and k-fold cross-validation for small test sets, and
      as new validation criteria, e.g. the density-fit metrics implemented in EDSTATS
      and ligand validation as implemented in YASARA. Innovative ways to present the
      refinement and validation results to the user are also described, which together
      with auto-generated Coot scripts can guide users to subsequent model inspection
      and improvement. It is demonstrated that using the server can lead to substantial
      improvement of structure models before they are submitted to the PDB. 

PMID- 25075343
TI  - Low-temperature catalyst activator: mechanism of dense carbon nanotube forest
      growth studied using synchrotron radiation.
AB  - The mechanism of the one-order-of-magnitude increase in the density of vertically
      aligned carbon nanotubes (CNTs) achieved by a recently developed thermal chemical
      vapor deposition process was studied using synchrotron radiation spectroscopic
      techniques. In the developed process, a Ti film is used as the underlayer for an
      Fe catalyst film. A characteristic point of this process is that C2H2 feeding for
      the catalyst starts at a low temperature of 450 degrees C, whereas conventional
      feeding temperatures are ~800 degrees C. Photoemission spectroscopy using soft
      and hard X-rays revealed that the Ti underlayer reduced the initially oxidized Fe
      layer at 450 degrees C. A photoemission intensity analysis also suggested that
      the oxidized Ti layer at 450 degrees C behaved as a support for nanoparticle
      formation of the reduced Fe, which is required for dense CNT growth. In fact, a
      CNT growth experiment, where the catalyst chemical state was monitored in situ by
      X-ray absorption spectroscopy, showed that the reduced Fe yielded a CNT forest at
      450 degrees C. Contrarily, an Fe layer without the Ti underlayer did not yield
      such a CNT forest at 450 degrees C. Photoemission electron microscopy showed that
      catalyst annealing at the conventional feeding temperature of 800 degrees C
      caused excess catalyst agglomeration, which should lead to sparse CNTs. In
      conclusion, in the developed growth process, the low-temperature catalyst
      activation by the Ti underlayer before the excess Fe agglomeration realised the
      CNT densification. 

PMID- 25075344
TI  - Aniline-phenol recognition: from solution through supramolecular synthons to
      cocrystals.
AB  - Aniline-phenol recognition is studied in the crystal engineering context in
      several 1:1 cocrystals that contain a closed cyclic hydrogen-bonded [?O-H?N-H?]2
      tetramer supramolecular synthon (II). Twelve cocrystals of 3,4,5- and 2,3,4
      trichlorophenol with one of eight halogenated anilines have been characterized.
      Ten of these cocrystals contain an extended octamer synthon that is assembled
      with hydrogen bonding and pi?pi stacking that defines a Long-Range Synthon Aufbau
      Module (LSAM). The design strategy is, therefore, based on the construction and
      transferability of the LSAM, which is a dimer of tetramers. Using the LSAM
      concept, two short cell axes in the crystal structures can be predicted. Whilst
      one of them is dictated by synthon II, the other one is dominated by pi?pi
      interactions. The third cell axis can also be predicted, in some cases, by
      systematic tuning of the halogen bonds. The design strategy is also verified in
      cocrystals of non-halogenated precursors. The observation of this large synthon
      in so many structures points to its stability and possible existence in solution.
      To this end, one-dimensional (1)H and (15)N NMR studies, performed on the 3,4,5
      trichlorophenol-3,5-dichloroaniline cocrystal in CDCl3, show characteristic
      downfield shifts that point to a pi?pi stacked structure and to the robustness of
      the hydrogen-bonded aggregates. Nuclear Overhauser effects point to hydrogen
      bonding between aniline and phenol molecules in the aggregates. Diffusion-ordered
      spectroscopy and T 1 inversion recovery experiments show that stacking is present
      in concentrated solution and lost at a certain dilution. A sequence of events is
      therefore established: molecules of the aniline and the phenol associate via
      hydrogen bonding to form tetramers, and tetramers subsequently stack to form
      octamers. 

PMID- 25075345
TI  - Structure and function study of the complex that synthesizes S
      adenosylmethionine.
AB  - S-Adenosylmethionine (SAMe) is the principal methyl donor of the cell and is
      synthesized via an ATP-driven process by methionine adenosyltransferase (MAT)
      enzymes. It is tightly linked with cell proliferation in liver and colon cancer.
      In humans, there are three genes, mat1A, mat2A and mat2B, which encode MAT
      enzymes. mat2A and mat2B transcribe MATalpha2 and MATbeta enzyme subunits,
      respectively, with catalytic and regulatory roles. The MATalpha2beta complex is
      expressed in nearly all tissues and is thought to be essential in providing the
      necessary SAMe flux for methylation of DNA and various proteins including
      histones. In human hepatocellular carcinoma mat2A and mat2B genes are
      upregulated, highlighting the importance of the MATalpha2beta complex in liver
      disease. The individual subunits have been structurally characterized but the
      nature of the complex has remained elusive despite its existence having been
      postulated for more than 20 years and the observation that MATbeta is often co
      localized with MATalpha2. Though SAMe can be produced by MAT(alpha2)4 alone, this
      paper shows that the V max of the MATalpha2beta complex is three- to fourfold
      higher depending on the variants of MATbeta that participate in complex
      formation. Using X-ray crystallography and solution X-ray scattering, the first
      structures are provided of this 258 kDa functional complex both in crystals and
      solution with an unexpected stoichiometry of 4alpha2 and 2betaV2 subunits. It is
      demonstrated that the N-terminal regulates the activity of the complex and it is
      shown that complex formation takes place surprisingly via the C-terminal of
      MATbetaV2 that buries itself in a tunnel created at the interface of the
      MAT(alpha2)2. The structural data suggest a unique mechanism of regulation and
      provide a gateway for structure-based drug design in anticancer therapies. 

PMID- 25075346
TI  - Diverse modes of binding in structures of Leishmania major N-myristoyltransferase
      with selective inhibitors.
AB  - The leishmaniases are a spectrum of global diseases of poverty associated with
      immune dysfunction and are the cause of high morbidity. Despite the long history
      of these diseases, no effective vaccine is available and the currently used drugs
      are variously compromised by moderate efficacy, complex side effects and the
      emergence of resistance. It is therefore widely accepted that new therapies are
      needed. N-Myristoyltransferase (NMT) has been validated pre-clinically as a
      target for the treatment of fungal and parasitic infections. In a previously
      reported high-throughput screening program, a number of hit compounds with
      activity against NMT from Leishmania donovani have been identified. Here, high
      resolution crystal structures of representative compounds from four hit series in
      ternary complexes with myristoyl-CoA and NMT from the closely related L. major
      are reported. The structures reveal that the inhibitors associate with the
      peptide-binding groove at a site adjacent to the bound myristoyl-CoA and the
      catalytic alpha-carboxylate of Leu421. Each inhibitor makes extensive apolar
      contacts as well as a small number of polar contacts with the protein.
      Remarkably, the compounds exploit different features of the peptide-binding
      groove and collectively occupy a substantial volume of this pocket, suggesting
      that there is potential for the design of chimaeric inhibitors with significantly
      enhanced binding. Despite the high conservation of the active sites of the
      parasite and human NMTs, the inhibitors act selectively over the host enzyme. The
      role of conformational flexibility in the side chain of Tyr217 in conferring
      selectivity is discussed. 

PMID- 25075347
TI  - Physical activity habits and preferences in the month prior to a first-ever
      stroke.
AB  - Background. Physical inactivity is a powerful risk factor for stroke and other
      chronic diseases. The aim of this study was to explore physical activity habits
      and preferences in the month leading up to a first-ever stroke, and to determine
      whether participants were aware of the link between stroke and physical activity.
      Methods. We undertook an observational study with 81 participants recently
      admitted to a stroke unit. Participants reported their pre-morbid physical
      activity preferences and habits and completed the Barriers to Physical Activity
      and Disability Survey. Data were analysed with summative content analysis and
      descriptive statistics. Results. Only 31% of participants were aware that
      physical inactivity was associated with stroke. Most participants defined
      physical activity with examples of instrumental activities of daily living (IADL)
      and walking (48% of responses), and IADLs constituted their most frequent regular
      physical activity (38% of responses). The barriers to physical activity reported
      by participants most frequently were lack of motivation (52%), lack of interest
      (50%) and lack of energy (42%). Conclusions. Regular physical activity is
      important to prevent stroke and other chronic diseases but adults at risk of
      stroke have little awareness of the risks of physical inactivity and little
      motivation to undertake regular exercise. 

PMID- 25075349
TI  - Where is Archives of Plastic Surgery Now? And Where is It Heading?

PMID- 25075350
TI  - Tumescent local anesthesia for hand surgery: improved results, cost
      effectiveness, and wide-awake patient satisfaction.
AB  - This is a review article of the wide-awake approach to hand surgery. More than
      95% of all hand surgery can now be performed without a tourniquet. Epinephrine is
      injected with lidocaine for hemostasis and anesthesia instead of a tourniquet and
      sedation. This is sedation-free surgery, much like a visit to a dental office.
      The myth of danger of using epinephrine in the finger is reviewed. The wide awake
      technique is greatly improving results in tendon repair, tenolysis, and tendon
      transfer. Here, we will explain its advantages. 

PMID- 25075351
TI  - Creation of consistent burn wounds: a rat model.
AB  - BACKGROUND: Burn infliction techniques are poorly described in rat models. An
      accurate study can only be achieved with wounds that are uniform in size and
      depth. We describe a simple reproducible method for creating consistent burn
      wounds in rats. METHODS: Ten male Sprague-Dawley rats were anesthetized and
      dorsum shaved. A 100 g cylindrical stainless-steel rod (1 cm diameter) was heated
      to 100C in boiling water. Temperature was monitored using a thermocouple. We
      performed two consecutive toe-pinch tests on different limbs to assess the depth
      of sedation. Burn infliction was limited to the loin. The skin was pulled
      upwards, away from the underlying viscera, creating a flat surface. The rod
      rested on its own weight for 5, 10, and 20 seconds at three different sites on
      each rat. Wounds were evaluated for size, morphology and depth. RESULTS: Average
      wound size was 0.9957 cm(2) (standard deviation [SD] 0.1845) (n=30). Wounds
      created with duration of 5 seconds were pale, with an indistinct margin of
      erythema. Wounds of 10 and 20 seconds were well-defined, uniformly brown with a
      rim of erythema. Average depths of tissue damage were 1.30 mm (SD 0.424), 2.35 mm
      (SD 0.071), and 2.60 mm (SD 0.283) for duration of 5, 10, 20 seconds
      respectively. Burn duration of 5 seconds resulted in full-thickness damage. Burn
      duration of 10 seconds and 20 seconds resulted in full-thickness damage,
      involving subjacent skeletal muscle. CONCLUSIONS: This is a simple reproducible
      method for creating burn wounds consistent in size and depth in a rat burn model.

PMID- 25075352
TI  - Transposition of intravascular lipid in experimentally induced fat embolism: a
      preliminary study.
AB  - BACKGROUND: Liposuction is a procedure to reduce the volume of subcutaneous fat
      by physical force. Intracellular storage fat is composed of triglyceride, whereas
      circulating fat particles exist as cholesterol or triglycerol bound to carrier
      proteins. It is unavoidable that the storage form of fat particles enters the
      circulation system after these particles are physiologically destroyed. To date,
      however, no studies have clarified the fatal characteristics of fat embolism that
      occurs after the subclinical phase of free fat particles. METHODS: A mixture of
      human lipoaspirate and normal saline (1:100, 0.2 mL) was injected into the
      external jugular vein of rats, weighing 200 g on average. Biopsy specimens of the
      lung and kidney were examined at 12-hour intervals until postoperative 72 hours.
      The deposit location and transport of the injected free fat particles were
      confirmed histologically by an Oil Red O stain. RESULTS: Inconsistent with
      previous reports, free fat particles were transported from the intravascular
      space to the parenchyma. At 24 hours after infusion, free fat particles deposited
      in the vascular lumen were confirmed on the Oil Red O stain. At 72 hours after
      infusion, free fat particles were accumulated compactly within the parenchymal
      space near the perivascular area. CONCLUSIONS: Many surgeons are aware of the
      fatal results and undiscovered pathophysiologic mechanisms of free fat particles.
      Our results indicate that free fat particles, the storage form of fat that has
      been degraded through a physiological process, might be removed through a direct
      transport mechanism and phagocytotic uptake.

PMID- 25075353
TI  - The use of matriderm and autologous skin graft in the treatment of full thickness
      skin defects.
AB  - BACKGROUND: For patients with full thickness skin defects, autologous Split
      thickness skin grafts (STSG) are generally regarded as the mainstay of treatment.
      However, skin grafts have some limitations, including undesirable outcomes
      resulting from scars, poor elasticity, and limitations in joint movement due to
      contractures. In this study, we present outcomes of Matriderm grafts used for
      various skin tissue defects whether it improves on these drawbacks. METHODS: From
      January 2010 to March 2012, a retrospective review of patients who had undergone
      autologous STSG with Matriderm was performed. We assessed graft survival to
      evaluate the effectiveness of Matriderm. We also evaluated skin quality using a
      Cutometer, Corneometer, Tewameter, or Mexameter, approximately 12 months after
      surgery. RESULTS: A total of 31 patients underwent STSG with Matriderm during the
      study period. The success rate of skin grafting was 96.7%. The elasticity value
      of the portion on which Matriderm was applied was 0.765 (range, 0.635-0.800), the
      value of the trans-epidermal water loss (TEWL) was 10.0 (range, 8.15-11.00)
      g/hr/m(2), and the humidification value was 24.0 (range, 15.5-30.0). The levels
      of erythema and melanin were 352.0 arbitrary unit (AU) (range, 299.25-402.75 AU)
      and 211.0 AU (range, 158.25-297.00 AU), respectively. When comparing the values
      of elasticity and TEWL of the skin treated with Matriderm to the values of the
      surrounding skin, there was no statistically significant difference between the
      groups. CONCLUSIONS: The results of this study demonstrate that a dermal
      substitute (Matriderm) with STSG was adopted stably and with minimal
      complications. Furthermore, comparing Matriderm grafted skin to normal skin using
      Cutometer, Matriderm proved valuable in restoring skin elasticity and the skin
      barrier.

PMID- 25075354
TI  - Management of defects on lower extremities with the use of matriderm and skin
      graft.
AB  - BACKGROUND: The reconstruction of large skin and soft tissue defects on the lower
      extremities is challenging. The skin graft is a simple and frequently used method
      for covering a skin defect. However, poor skin quality and architecture are well
      known problems that lead to scar contracture. The collagen-elastin matrix,
      Matriderm, has been used to improve the quality of skin grafts; however, no
      statistical and objective review of the results has been reported. METHODS:
      Thirty-four patients (23 male and 11 female) who previously received a skin graft
      and simultaneous application of Matriderm between January 2010 and June 2012 were
      included in this study. The quality of the skin graft was evaluated using
      Cutometer, occasionally accompanied by pathologic findings. RESULTS: All 34
      patients showed good skin quality compared to a traditional skin graft and were
      satisfied with their results. The statistical data for the measurement of the
      mechanical properties of the skin were similar to those for normal skin. In
      addition, there was no change in the engraftment rate. CONCLUSIONS: The biggest
      problem of a traditional skin graft is scar contracture. However, the dermal
      matrix presents an improvement in skin quality with elastin and collagen.
      Therefore, a skin graft along with a simultaneous application of Matriderm is
      safe and effective and leads to a significantly better outcome from the
      perspective of skin elasticity.

PMID- 25075355
TI  - Platybasia in 22q11.2 deletion syndrome is not correlated with speech resonance.
AB  - BACKGROUND: An abnormally obtuse cranial base angle, also known as platybasia, is
      a common finding in patients with 22q11.2 deletion syndrome (22q11DS). Platybasia
      increases the depth of the velopharynx and is therefore postulated to contribute
      to velopharyngeal dysfunction. Our objective was to determine the clinical
      significance of platybasia in 22q11DS by exploring the relationship between
      cranial base angles and speech resonance. METHODS: In this retrospective chart
      review at a tertiary hospital, 24 children (age, 4.0-13.1 years) with 22q11.2DS
      underwent speech assessments and lateral cephalograms, which allowed for the
      measurement of the cranial base angles. RESULTS: One patient (4%) had hyponasal
      resonance, 8 (33%) had normal resonance, 10 (42%) had hypernasal resonance on
      vowels only, and 5 (21%) had hypernasal resonance on both vowels and consonants.
      The mean cranial base angle was 136.5 degrees  (standard deviation, 5.3 degrees ;
      range, 122.3-144.8 degrees ). The Kruskal-Wallis test showed no significant
      relationship between the resonance ratings and cranial base angles (P=0.242).
      Cranial base angles and speech ratings were not correlated (Spearman
      correlation=0.321, P=0.126). The group with hypernasal resonance had a
      significantly more obtuse mean cranial base angle (138 degrees  vs. 134 degrees ,
      P=0.049) but did not have a greater prevalence of platybasia (73% vs. 56%,
      P=0.412). CONCLUSIONS: In this retrospective chart review of patients with
      22q11DS, cranial base angles were not correlated with speech resonance. The
      clinical significance of platybasia remains unknown.

PMID- 25075356
TI  - Comparison study of the use of absorbable and nonabsorbable materials as internal
      splints after closed reduction for nasal bone fracture.
AB  - BACKGROUND: The authors sought to compare the use of the nonabsorbable polyvinyl
      alcohol sponge (PVA, Merocel) and absorbable synthetic polyurethane foam (SPF,
      Nasopore Forte plus) as intranasal splints after closed reduction of fractured
      nasal bones during the hospitalization period. METHODS: The medical records of
      111 patients who underwent closed reduction for nasal bone fracture at Sanggye
      Paik Hospital, Inje University College of Medicine, from 2012 to 2013 were
      reviewed retrospectively. PVA (group A) or SPF (group B) was packed as an
      internal splint after closed reduction. The efficacy of the materials was
      compared and statistically analyzed. RESULTS: PVA was used in 82 patients, and
      SPF was used in 29 patients. The patients in group B complained significantly
      more of nasal pain on the first day after operation than the patients in group A.
      Headaches on the operation day were significantly more painful in group B than in
      group A. Bleeding on the fourth postoperative day was significantly reduced in
      group B as compared to group A. The patients in group B exhibited significantly
      more intensive nasal obstruction on the operation day and the following day than
      the patients in group A. However, on the third and fourth postoperative days, the
      nasal obstruction in group B was less than that in group A. The pain and bleeding
      related to the packing material was significantly reduced in group B as compared
      to group A. CONCLUSIONS: The use of SPF as an absorbable packing material is a
      reasonable substitute for the traditional nonabsorbable material.

PMID- 25075357
TI  - Comparison of Absorbable Mesh Plate versus Titanium-Dynamic Mesh Plate in
      Reconstruction of Blow-Out Fracture: An Analysis of Long-Term Outcomes.
AB  - BACKGROUND: A blow-out fracture is one of the most common facial injuries in
      midface trauma. Orbital wall reconstruction is extremely important because it can
      cause various functional and aesthetic sequelae. Although many materials are
      available, there are no uniformly accepted guidelines regarding material
      selection for orbital wall reconstruction. METHODS: From January 2007 to August
      2012, a total of 78 patients with blow-out fractures were analyzed. 36 patients
      received absorbable mesh plates, and 42 patients received titanium-dynamic mesh
      plates. Both groups were retrospectively evaluated for therapeutic efficacy and
      safety according to the incidence of three different complications: enophthalmos,
      extraocular movement impairment, and diplopia. RESULTS: For all groups (inferior
      wall fracture group, medial wall fractrue group, and combined inferomedial wall
      fracture group), there were improvements in the incidence of each complication
      regardless of implant types. Moreover, a significant improvement of enophthalmos
      occurred for both types of implants in group 1 (inferior wall fracture group).
      However, we found no statistically significant differences of efficacy or
      complication rate in every groups between both implant types. CONCLUSIONS: Both
      types of implants showed good results without significant differences in long
      term follow up, even though we expected the higher recurrent enophthalmos rate in
      patients with absorbable plate. In conclusion, both types seem to be equally
      effective and safe for orbital wall reconstruction. In particular, both implant
      types significantly improve the incidence of enophthalmos in cases of inferior
      orbital wall fractures.

PMID- 25075358
TI  - Safety of silastic sheet for orbital wall reconstruction.
AB  - BACKGROUND: Many implants are being used for the reconstruction of orbital wall
      fractures. The effect of the choice of implant for the reconstruction of an
      orbital wall fracture on the surgical outcome is under debate. The purpose of
      this article is to compare the outcomes of orbital wall reconstruction of small
      orbital wall fractures on the basis of the implants used. METHODS: The authors
      conducted a retrospective study using electronic databases. Between March 2001
      and December 2012, 461 patients with orbital wall fractures were included in this
      study. Among them, 431 patients in whom the fracture size was less than 300 mm(2)
      were analyzed. The fracture size was calculated using computed tomography scans
      of the orbit in the sagittal and coronal images. Cases in which the fracture size
      was less than 300 mm(2) were included in this study. RESULTS: One hundred and
      twenty-nine patients were treated with silastic sheets; 238 patients were treated
      with titanium meshes; and absorbable meshes were used in the case of 64 patients.
      Overall, 13 patients required revision, and the revision rate was 3.0%. The
      revision rate of the silastic sheet group was 5.4%. In the multivariable
      analysis, the revision rate of the group reconstructed with silastic sheets was
      highly statistically significant (P=0.043, odds ratio=3.65). However, other
      factors such as age, sex, fracture type, and fracture size were not significant.
      CONCLUSIONS: Reconstruction of orbital wall fractures with silastic sheets may
      cause more complications than that with other materials such as titanium meshes
      and absorbable meshes.

PMID- 25075359
TI  - Aesthetic design of skin-sparing mastectomy incisions for immediate autologous
      tissue breast reconstruction in asian women.
AB  - BACKGROUND: The advent of skin-sparing mastectomy has allowed for the
      reconstruction of the breast and nipple with improved cosmesis. However, the
      nipple-areolar complex (NAC) in Asian patients is more pigmented and scars
      easily. Therefore, commonly described incisions tend to result in poor aesthetic
      outcomes in Asian patients with breast cancer. METHODS: We describe an
      algorithmic approach to skin-sparing mastectomy incisions in Asian patients on
      the basis of the location of the biopsy scar and the tumor site and size. Four
      incision types are described: peri-areolar, a peri-areolar incision with a second
      distant skin paddle, "racquet handle," and peri-areolar with adjacent skin
      excision. RESULTS: 281 immediate breast reconstructions were performed between
      May 2001 and February 2012 after skin-sparing mastectomy. The mastectomy
      incisions used included the peri-areolar design (n=124, 44%), peri-areolar design
      with a second distant skin paddle (n=39, 14%), "racquet handle" (n=21, 7.5%), and
      peri-areolar design with adjacent skin excision (n=42, 14%). The traditional
      elliptical incision and other variants where the NAC outline was not preserved
      were performed in the remaining 55 patients. The average follow-up was 44.7
      months during which there was 1 case of total flap loss and 7 cases of partial
      flap necrosis; all remaining flaps survived. 24% of the patients (68/281)
      underwent subsequent nipple reconstruction. CONCLUSIONS: Our algorithm avoids
      breast incisions that are randomly placed or excessively long and prevents the
      unnecessary sacrifice of normal breast skin. This allows skin-sparing mastectomy
      and immediate breast reconstruction to be performed with a consistently
      achievable aesthetic result in Asian women without neglecting oncological safety.

PMID- 25075360
TI  - Clinical experience with treatment of angioleiomyoma.
AB  - BACKGROUND: Angioleiomyoma, a vascular leiomyoma, is a rare, benign smooth-muscle
      tumor that originates in the tunica media of vessels. It occurs anywhere in the
      body, most frequently in the lower extremities. METHODS: We reviewed the medical
      records of 16 patients who were treated for angioleiomyoma between 2000 and 2012.
      The clinical features of angioleiomyoma and the correlation between symptoms and
      pathological subtypes were investigated. RESULTS: There were 9 males and 6
      females. Ages of the patients ranged from 21 to 61. Pain was the primary symptom
      in 44% of the patients. Tumors were smaller than 2.0 cm in all dimensions and
      were located in the face in 4 patients, whereas 5 lesions occurred in the upper
      extremities and the remaining 7 in the lower extremities. Three histologic
      subtypes were identified: solid, venous, and cavernous. The subtypes did not
      correlate with the clinical symptoms. CONCLUSIONS: Angioleiomyoma appears to be a
      rare tumor that occurs in the face and the extremities. The tumor usually occurs
      in middle age. A differential diagnosis of this tumor is difficult, but the tumor
      should be considered in the diagnosis of painful subcutaneous masses.
      Ultrasonography and magnetic resonance imaging can be helpful in the diagnosis of
      angioleiomyoma. These tumors can be successfully treated with simple excision,
      with a low recurrence rate.

PMID- 25075361
TI  - Subunit principle of vulvar reconstruction: algorithm and outcomes.
AB  - BACKGROUND: Vulvar defects result chiefly from oncologic resection of vulvar
      tumors. Reconstruction of vulvar defects restores form and function for the
      purpose of coitus, micturition, and defecation. Many surgical options exist for
      vulvar reconstruction. The purpose of this article is to present our experience
      with vulvar reconstruction. METHODS: From 2007 to 2013, 43 women presented to us
      with vulvar defects for reconstruction. Their mean age at the time of
      reconstruction was 61.1 years. The most common cause of vulvar defect was from
      resection of vulvar carcinoma and extramammary Paget's disease of the vulva.
      Method s of reconstruction ranged from primary closure to skin grafting to the
      use of pedicled flaps. RESULTS: The main complications were that of long term
      hypertrophic and/or unaesthetic scarring of the donor site in 4 patients. Twenty
      two patients (51%) were able to resume sexual intercourse. There were no
      complications of flap loss, wound dehiscence, and urethral stenosis. CONCLUSIONS:
      We present a subunit algorithmic approach to vulvar reconstruction based on
      defect location within the vulva, dimension of the defect, and patient age and
      comorbidity. The gracilis and gluteal fold flaps are particularly versatile and
      aesthetically suited for reconstruction of a variety of vulvar defects. From an
      aesthetic viewpoint the gluteal fold flap was superior because of the well
      concealed donor scar. We advocate the routine use of these 2 flaps for vulvar
      reconstruction.

PMID- 25075362
TI  - Treatment of ischial pressure sores with both profunda femoris artery perforator
      flaps and muscle flaps.
AB  - BACKGROUND: Reconstruction of ischial pressure sore defects is challenging due to
      extensive bursas and high recurrence rates. In this study, we simultaneously
      applied a muscle flap that covered the exposed ischium and large bursa with
      sufficient muscular volume and a profunda femoris artery perforator
      fasciocutaneous flap for the management of ischial pressure sores. METHODS: We
      retrospectively analyzed data from 14 patients (16 ischial sores) whose ischial
      defects had been reconstructed using both a profunda femoris artery perforator
      flap and a muscle flap between January 2006 and February 2014. We compared
      patient characteristics, operative procedure, and clinical course. RESULTS: All
      flaps survived the entire follow-up period. Seven patients (50%) had a history of
      surgery at the site of the ischial pressure sore. The mean age of the patients
      included was 52.8 years (range, 18-85 years). The mean follow-up period was 27.9
      months (range, 3-57 months). In two patients, a biceps femoris muscle flap was
      used, while a gracilis muscle flap was used in the remaining patients. In four
      cases (25%), wound dehiscence occurred, but healed without further complication
      after resuturing. Additionally, congestion occurred in one case (6%), but
      resolved with conservative treatment. Among 16 cases, there was only one (6%)
      recurrence at 34 months. CONCLUSIONS: The combination of a profunda femoris
      artery perforator fasciocutaneous flap and muscle flap for the treatment of
      ischial pressure sores provided pliability, adequate bulkiness and few long-term
      complications. Therefore, this may be used as an alternative treatment method for
      ischial pressure sores.

PMID- 25075363
TI  - Proximal interphalangeal joint dislocations and treatment: an evolutionary
      process.
AB  - BACKGROUND: Proximal interphalangeal joint (PIPJ) dislocations represent a
      significant proportion of hand clinic visits and typically require frequent
      follow-ups for clinical assessment, orthotic adjustments, and physiotherapy.
      There are a large number of treatment options available for PIPJ dislocations,
      yet no prospective or controlled studies have been carried out, largely due to
      the diversity of the various types of injuries. METHODS: We retrospectively
      reviewed all the PIPJ dislocations in our institution over a five-year period and
      directly compared the different splinting techniques that we have used over this
      time frame. RESULTS: There were a total of 77 dislocations of the PIPJ (57 men
      and 20 women) that were included in our study. We found that our management has
      shifted gradually from complete immobilisation to controlled early mobilisation
      with figure-of-eight splints. Following treatment, the range of motion of the
      PIPJ in the figure-of-eight group was significantly greater than that in the
      other three methods (P<0.05) used. There were significantly fewer hospital visits
      in the figure-of-eight splint group than in the other treatment groups.
      CONCLUSIONS: The treatment of PIPJ dislocations has undergone a significant
      evolution in our experience. Early controlled mobilisation has become
      increasingly important, and therefore, splints have had to be adapted to allow
      for this. The figure-of-eight splint has yielded excellent results in our
      experience. It should be considered for all PIPJ dislocations, but careful
      patient selection is required to achieve optimum results.

PMID- 25075364
TI  - Tarsodermal suture fixation preceding redundant skin excision: a modified non
      incisional upper blepharoplasty method for elderly patients.
AB  - BACKGROUND: Non-incisional blepharoplasty is a simple, less invasive method for
      creating a more natural-appearing double eyelid than classical incisional
      blepharoplasty. However, in aging patients, non-incisional blepharoplasty is not
      effective due to more severe blepharochalasis. Traditionally, incisional
      blepharoplasty is a common surgical method used for older patients, but
      blepharoplasty in elderly patients typically results in prolonged recovery times,
      and final blepharoplasty lines may be located in unintended or asymmetrical
      positions. Here, we introduce a new modified combination technique for geriatric
      blepharoplasty. METHODS: A total of ten patients were treated from July 2010
      through July 2012 using the combination method. First, we performed non
      incisional blepharoplasty using tarsodermal fixation. Then, incisional
      blepharoplasty with additional elliptical excision of the upper eyelid skin was
      performed. We removed pretarsal tissue, fat, the orbicularis oculi muscle, and
      orbital fat. Telephone surveys were administered to all patients for follow-up.
      The questionnaire was composed of eight questions that addressed recurrence and
      satisfaction with aesthetics and the procedure. RESULTS: A total of nine patients
      (90%) responded to the telephone survey. All cases of moderate to severe
      blepharochalasia were corrected and there were no major complications. Patients
      who underwent blepharoplasty had higher satisfaction scores. All patients were
      satisfied with the postoperative shapes of their eyelids. CONCLUSIONS: THE
      ADVANTAGES OF THE PROPOSED TECHNIQUE INCLUDE: ease of obtaining a natural-looking
      fold with symmetry at the desired point; reproducible methods that require short
      operation times; fast postoperative recovery that results in a natural-appearing
      double-eyelid line; and high patient satisfaction.

PMID- 25075365
TI  - A new approach to objective evaluation of the success of nasal septum
      perforation.
AB  - BACKGROUND: Perforations in the nasal septum (NSP) give rise not only to
      disintegration of the septum anatomy but also impairment in normal nasal
      physiology. The successes of these surgical techniques are usually equated to
      anatomical closure of the perforation. The goal of this study is to evaluate the
      subjective and objective results of our surgical technique for septal perforation
      surgery. METHODS: All NSPs in the six patients were closed by inferior turbinate
      flap. The Nasal Obstruction Symptom Evaluation (NOSE) instrument was used to
      evaluate the preoperative and postoperative subjective sensation of nasal
      obstruction. Measurement of preoperative and postoperative nasal airway
      resistance was performed using active anterior rhinomanometry which is an
      objective test. Wilcoxson signed rank test and Spearman correlation test were
      used to analyze correlation between NOSE scores and rhinomanometric measurements.
      RESULTS: The full closure of the septal perforations was noted in 100% of
      patients. The total NOSE score was 14 preoperatively and one postoperatively. The
      improvement in NOSE scores was statistically significant (P<=0.002). The mean
      preoperative total resistance (ResT150) value was 0.13 Pa/cm(3)s(-1), which is
      below the normal range (0.16-0.31 Pa/cm(3)s(-1)), while the mean postoperative
      ResT150 value was 0.27 Pa/cm(3)s(-1). The correlation between the improvement in
      NOSE scores and improvements in ResT150 values was statistically significant.
      CONCLUSIONS: Surgical approaches should aim to solve both the anatomical and
      physiological problems of NSP. The application of subjective and objective tests
      in the postoperative period will help surgeons assess the applied techniques.

PMID- 25075366
TI  - Prevention of implant malposition in inframammary augmentation mammaplasty.
AB  - BACKGROUND: Implant malposition can produce unsatisfactory aesthetic results
      after breast augmentation. The goal of this article is to identify aspects of the
      preoperative surgical planning and intraoperative flap fixation that can prevent
      implant malposition. METHODS: This study examined 36 patients who underwent
      primary dual plane breast augmentation through an inframammary incision between
      September 1, 2012 and January 31, 2013. Before the surgery, preoperative
      evaluation and design using the Randquist formula were performed. Each patient
      was evaluated retrospectively for nipple position relative to the breast implant
      and breast contour, using standardized preoperative and postoperative
      photographs. The average follow-up period was 10 months. RESULTS: Seven of 72
      breasts were identified as having implant malposition. These malpositions were
      divided into two groups. In relation to the new breast mound, six breasts had an
      inferiorly positioned and one breast had a superiorly positioned nipple-areolar
      complex. Two of these seven breasts were accompanied with an unsatisfactory
      breast contour. CONCLUSIONS: We identified two main causes of implant malposition
      after inframammary augmentation mammaplasty. One cause was an incorrect
      preoperatively designed nipple to inframammary fold (N-IMF) distance. The breast
      skin and parenchyma quality, such as an extremely tight envelope, should be
      considered. If an extremely tight envelope is found, the preoperatively designed
      new N-IMF distance should be increased. The other main cause of malposition is
      failure of the fascial suture from Scarpa's fascia to the perichondrium through
      an inframammary incision. As well, when this fixation is performed, it should be
      performed directly downward to the perichondrium, rather than slanted in a
      cranial or caudal direction.

PMID- 25075367
TI  - The story of serratia marcescens: pathologic risk factors in breast implant
      surgery.
AB  - Serratia marcescens (S. marcescens) emerged as an opportunist in the setting of
      immunodeficiency in the 1970s, when serious infections occurred in San Francisco
      hospitals after USA. Navy experiments had aerosolized the bacteria to study
      biologic warfare. We investigate the risks of S. marcescens in San Franciscans
      who undergo mastectomy with implant reconstruction. From 2007 to 2011, the senior
      author took breast capsule cultures for all patients at the time of tissue
      expander exchange/explant. Of the 142 women who had reconstruction, 23 had
      positive cultures. Only the two patients who were positive for S. marcescens
      developed clinical infections that required explantation. Both had postoperative
      chemotherapy with transient neutropenia, and both had close ties to San
      Francisco. Clinical signs of infection emerged for both patients months after
      initial surgery, despite having previously well healed incisions. Other patients
      were culture positive for Pseudomonas, Proteus, Enterococcus and MRSA and did not
      develop require explant. While the link between San Francisco and S. marcescens
      is controversial, a patient's geography is a simple screening tool when
      considering postoperative risks, especially in the immunocompromised. Closer
      monitoring for neutropenia during chemotherapy, and a lower threshold to
      administer S. marcescens targeted antibiotics may be warranted in these patients.

PMID- 25075368
TI  - A new modality for treating congenital melanocytic nevus: "cogwheel pattern"
      serial excision method.
AB  - Congenital melanocytic nevus consists of congregations of nevomelanocytes. It is
      found in approximately 1% of new born infants. Congenital melanocytic nevus needs
      to be excised before it transforms into a malignant lesion. Many strategies have
      been attempted for the removal and reconstruction of the nevus. Serial excision
      enables wound closure to be accomplished with a shorter scar than if the original
      lesion was elliptically excised in a single stage and reorientation of the scar
      closer to the relaxed skin lines. The routine utilization of an elliptical serial
      excision as a standard method of closure often leads to the formation of
      elongated scars and waste of skin. The "Cogwheel pattern" serial excision is a
      new technique for reducing the size of the nevus efficiently. Reducing the final
      scar length, distributing the tension over many directions, and having the chance
      of decrease in operation numbers are ultimately achieved with the use of the
      "Cogwheel pattern" serial excision. 

PMID- 25075369
TI  - Glove vacuum-assisted wound closure for the scrotum.

PMID- 25075370
TI  - Facial Cushioning during Prolonged Surgery in the Upper Torso.

PMID- 25075371
TI  - Dry dressing for epidermal sloughing after subcutaneous azacitidine injection in
      a myelodysplastic syndrome.

PMID- 25075372
TI  - Surgical correction of an accessory auricle, polyotia.

PMID- 25075373
TI  - Congenital midline cervical cleft.

PMID- 25075374
TI  - A rare case of postoperative traumatic optic neuropathy in orbital floor
      fracture.

PMID- 25075375
TI  - Penetrating trans-orbital injury from a brush handle lodged in the infra-temporal
      fossa.

PMID- 25075376
TI  - Giant eccrine hidradenoma mimicking a malignant tumor of the salivary gland.

PMID- 25075377
TI  - A modified total thigh flap in the reconstruction of decubitus ulcer.

PMID- 25075378
TI  - Pneumomediastinum after facial bone contouring surgery.

PMID- 25075379
TI  - Social networking and plastic surgery education: running international plastic
      surgery.

PMID- 25075380
TI  - Effects of educational intervention based on PRECEDE model on self care behaviors
      and control in patients with type 2 diabetes in 2012.
AB  - BACKGROUND: Diabetes is a chronic disease and its control requires essential
      change in patients' life style. The aim of this study was survey of effects of
      educational intervention based on PRECEDE Model on self care behaviors and
      control in patients with type 2 diabetes. METHODS: This was a quasi-experimental
      study carried out in 78 patients with type 2 diabetes who have referred to
      Minoodasht clinic of diabetes. The educational program has been designed
      according to the PRECEDE Model. Prior to perform the educational intervention,
      the patients filled a questionnaire which was designed according to the structure
      of PRECEDE Model for type 2 diabetes patients. The diabetes education program was
      performed on three target groups (patients, their families and Health care
      personnel). After four weeks, the effects of the educational program have been
      evaluated through the same questionnaire. The findings were analyzed by SPSS
      version 16 and p-value less than 0.05 was taken as statistically significant.
      RESULTS: The mean age of participants was 49 years, 87.2% were married and 19.2%
      was illiterate. The rate of income of 44.9% was low. 66% had a family history of
      diabetes and 64% had been afflicted with diabetes more than 5 years. The Chi
      square test showed a significant relationship between formation of a file in
      diabetes clinic and on-time presence to receive services and participation in the
      educational classes with the marital status variable. The results also showed
      that there is a significant relationship between observing food diet and job. The
      mean scores of knowledge, attitude, practice, reinforcing factors and enabling
      factors has increased after educational intervention. The Chi-square test shows a
      significant difference before and after of education intervention in stages of
      the model. CONCLUSION: The obtained results based on PRECEDE Model would support
      the positive effect of the educational intervention and its major elements
      (predisposing, enabling and reinforcing factors) on diabetes self-care behaviors.

PMID- 25075381
TI  - Predicting mechanism of biphasic growth factor action on tumor growth using a
      multi-species model with feedback control.
AB  - A large number of growth factors and drugs are known to act in a biphasic manner:
      at lower concentrations they cause increased division of target cells, whereas at
      higher concentrations the mitogenic effect is inhibited. Often, the molecular
      details of the mitogenic effect of the growth factor are known, whereas the
      inhibitory effect is not. Hepatoctyte Growth Factor, HGF, has recently been
      recognized as a strong mitogen that is present in the microenvironment of solid
      tumors. Recent evidence suggests that HGF acts in a biphasic manner on tumor
      growth. We build a multi-species model of HGF action on tumor cells using
      different hypotheses for high dose-HGF activation of a growth inhibitor and show
      that the shape of the dose-response curve is directly related to the mechanism of
      inhibitor activation. We thus hypothesize that the shape of a dose-response curve
      is informative of the molecular action of the growth factor on the growth
      inhibitor.

PMID- 25075383
TI  - International wound care: setting the bar high.

PMID- 25075382
TI  - A napthelene-pyrazol conjugate: Al(III) ion-selective blue shifting chemosensor
      applicable as biomarker in aqueous solution.
AB  - A newly synthesized and crystalographically characterized napthelene-pyrazol
      conjugate, 1-[(5-phenyl-1H-pyrazole-3-ylimino)-methyl]-naphthalen-2-ol (HL)
      behaves as an Al(III) ion-selective chemosensor through internal charge transfer
      (ICT)-chelation-enhanced fluorescence (CHEF) processes in 100 mM HEPES buffer
      (water-DMSO 5:1, v/v) at biological pH with almost no interference of other
      competitive ions. This mechanism is readily studied from electronic, fluorimetric
      and (1)H NMR titration. The probe (HL) behaved as a highly selective fluorescent
      sensor for Al(III) ions as low as 31.78 nM within a very short response time (15
      20 s). The sensor (HL), which has no cytotoxicity, is also efficient in detecting
      the distribution of Al(III) ions in HeLa cells via image development under
      fluorescence microscope.

PMID- 25075384
TI  - Older people and skin: challenging perceptions.
AB  - In this article we set out to challenge perceptions about older people and skin.
      We examine current portrayals of older people and skin, both in the media and in
      the nursing literature. We describe the 'normal' process of skin ageing and
      highlight the importance of maintaining skin integrity and effective barrier
      function for health and wellbeing, particularly in older people. One element of
      maintaining skin integrity is ensuring that personal hygiene and emollient needs
      are met. Effective skin hygiene and emollient care will reduce the risk of
      breakdown, with all its burdensome and costly consequences. We therefore offer a
      summary of the current evidence base for skin-hygiene practice. We make a case
      for nurses considering skin health from a wider societal and human perspective,
      and identify opportunities to enhance nursing practice through skin-care advice
      and health education for all older people.

PMID- 25075385
TI  - Understanding methods of wound debridement.
AB  - Autolytic debridement describes the body's natural method of wound-bed cleansing,
      helping it to prepare the wound bed for healing. In acute wounds, autolytic
      debridement occurs automatically and often does not require intervention, as
      during the inflammatory stage of a wound, neutrophils and macrophages digest and
      removes devitalised tissue, cell debris and contaminants, clearing the wound of
      any cellular barriers to healing. In chronic wounds, by contrast, healing is
      often delayed, frequently because of inadequate debridement. The autolytic
      process becomes overwhelmed by high levels of endotoxins released from damaged
      tissue (Broadus, 2013). Therefore wound debridement becomes an integral part of
      chronic-wound management and practitioners involved in wound care must be fully
      competent at wound-bed assessment and have an awareness of the options available
      for debridement. This article will review wound-bed assessment, highlighting
      variations in devitalised tissue, and explore options available for wound
      debridement, taking into consideration patients' pain and quality of life.

PMID- 25075386
TI  - Accelerate Health Community Interest Company: an interview.

PMID- 25075387
TI  - Functional independence in teenage patients with burns.
AB  - The purpose of this study was to assess the functional independence of teenagers
      undergoing a process of rehabilitation. A cross-sectional study was carried out
      on a sample of 63 teenagers, aged 12 to 20, who had suffered burns and were going
      through a process of rehabilitation, with the application of the Functional
      Independence Measurement (FIM). The data was analysed using descriptive
      statistics and also a test for comparison of means (Student's t-test), as well as
      Cronbach's reliability test. There was proof of a high degree of independence in
      FIM. Analysis of the location of the burn and also the performance of work and/or
      study activities showed these not to interfere with functional independence. The
      results indicate the reliability of the instruments applied, making it possible
      to conduct an assessment of the functional independence of the teenagers during
      the rehabilitation process.

PMID- 25075388
TI  - Differences between medical devices and drugs.

PMID- 25075390
TI  - Looking to the long term: choosing the right dressing.

PMID- 25075391
TI  - Phage therapies for plants and people.
AB  - The use of bacteriophages to combat bacterial infections may help to address the
      current crisis of antibiotic resistance. Fundamental issues arising from the
      ecological dynamic of host, bacterium and phage can be investigated in trees,
      offering both a natural approach to treating plant disease, and a chance to avoid
      creating a new resistance problem. Michael Gross reports.

PMID- 25075389
TI  - Quality dressings and assessment.

PMID- 25075392
TI  - Dolf Seilacher (1925-2014).

PMID- 25075393
TI  - Marie Dacke.

PMID- 25075394
TI  - Supporting family caregivers.

PMID- 25075395
TI  - Worsening renal function in patients with acute decompensated heart failure
      treated with ultrafiltration: predictors and outcomes.
AB  - BACKGROUND: Ultrafiltration (UF) is used to treat patients with diuretic
      resistant acute decompensated heart failure. The aim of this study was to
      identify predictors and the effect of worsening renal failure(WRF) on mortality
      in patients treated with UF. METHODS AND RESULTS: Based on changes in serum
      creatinine, 99 patients treated with UF were divided into WRF and control groups.
      Overall creatinine increased from 1.9 +/- 0.7 to 1.2 +/- 1.0 mg/dL (P!.001),and
      WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF
      group in univariate analysis (174 +/- 75 vs 144 +/- 52 mL/h; P = .03). Based on
      multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38,
      95% confidence interval [CI] 1.17-13.46, P = .04), heart rate <=65 beats/min (OR
      6.03, 95% CI 1.48-48.42; P = .03), and E/E0 >= 15 (OR 3.78, 95% CI 1.26-17.55; P
      5 .04) at hospital admission were associated with WRF. Patients with baseline
      glomerular filtration rate (GFR) <=60mg/dL who developed WRF during UF had a 75%
      1-year mortality rate. CONCLUSIONS: WRF occurred frequently during UF. Increased
      LV filling pressures, lower heart rate, and treatment with aldosterone antagonist
      at hospital admission can identify patients at increased risk for WRF. Patients
      with baseline GFR <=60 mg/dL and WRF during UF have an extremely high 1-year
      mortality rate.

PMID- 25075396
TI  - Author's reply.

PMID- 25075397
TI  - Author's Reply.

PMID- 25075399
TI  - Author's Reply.

PMID- 25075398
TI  - Illness representations of restricting back pain: the older Person's perspective.
AB  - OBJECTIVE: Back pain is the most common type of pain reported by older adults,
      leading to considerable morbidity and cost. Yet little is known about the segment
      of the population >=80 years old that can be used to guide care in this age
      group. Illness representations provide a useful framework to understand older
      adults' beliefs and perceptions of their back pain. The objective of this study
      was to understand illness representations of back pain, severe enough to restrict
      activity (restricting back pain). DESIGN: Qualitative research using semi
      structured interviews. SUBJECTS: Twenty-three community-living older adults >=80
      years old with restricting back pain. METHODS: We used an interview guide to
      stimulate discussion about how older adults understand and perceive living with
      restricting back pain. Thematic codes were created to categorize the nuances of
      participants' restricting back pain experiences. RESULTS: Participants reported
      five important components of illness representation: 1) identity,the label and
      symptoms individuals assign to the illness; 2) timeline, the individual's
      perceived clinical course of the illness; 3) cause, the individual's perceived
      etiology of the illness; 4) consequences,the perceived impact of the illness; and
      5) cure control,the perceived degree to which cure or management is
      possible/likely. CONCLUSIONS: Thematic analysis revealed that restricting back
      pain in older adults has variable and noteworthy physical, psychological and
      social consequences.There are several components of the illness representation of
      restricting back pain, specifically,the perceptions of consequences and control
      that may offer potential targets for clinical intervention.

PMID- 25075400
TI  - Author's Reply.

PMID- 25075401
TI  - Author's Reply.

PMID- 25075403
TI  - Cardiology in Russia.

PMID- 25075402
TI  - Improving prediction of type 1 diabetes by testing non-HLA genetic variants in
      addition to HLA markers.
AB  - OBJECTIVE: The purpose of this study was to explore whether non-human leukocyte
      antigen (non-HLA) genetic markers can improve type 1 diabetes(T1D) prediction in
      a prospective cohort with high-risk HLA-DR,DQ genotypes. METHODS: The Diabetes
      Autoimmunity Study in the Young (DAISY) follows prospectively for the development
      of T1D and islet autoimmunity (IA)children at increased genetic risk. A total of
      1709 non-Hispanic White DAISY participants have been genotyped for 27 non-HLA
      single nucleotide polymorphisms (SNPs) and one microsatellite. RESULTS: In
      multivariate analyses adjusting for family history and HLA-DR3/4 genotype, PTPN22
      (rs2476601) and two UBASH3A (rs11203203 and rs9976767) SNPs were associated with
      development of IA [hazard ratio(HR)=1.87, 1.55, and 1.54, respectively, all p <=
      0.003], while GLIS3 and IL2RA showed borderline association with development of
      IA. INS,UBASH3A, and IFIH1 were significantly associated with progression from IA
      to diabetes (HR=1.65, 1.44, and 1.47, respectively, all p <= 0.04), while PTPN22
      and IL27 showed borderline association with progression from IA to diabetes. In
      survival analysis, 45% of general population DAISY children with PTPN22 rs2476601
      TT or HLA-DR3/4 and UBASH3A rs11203203 AA developed diabetes by age 15, compared
      with 3% of children with all other genotypes (p<0.0001). Addition of non-HLA
      markers to HLA-DR3/4,DQ8 did not improve diabetes prediction in first-degree
      relatives. CONCLUSION: Addition of PTPN22 and UBASH3A SNPs to HLA-DR,DQ
      genotyping can improve T1D risk prediction.

PMID- 25075404
TI  - [Alopecia in cancer patients: traumatic and stigmatising].

PMID- 25075405
TI  - Added sugars and cardiovascular diseases.

PMID- 25075406
TI  - Human metabolic disease: lessons from the extremes.

PMID- 25075407
TI  - The effects of obesity and ageing on the heart: are  they so different?

PMID- 25075408
TI  - Medical research could soon be jeopardized by new European Union data protection
      regulations.

PMID- 25075409
TI  - [Bureaucracy and quality in a reciprocal relationship or "bureaucracy devours
      quality"].

PMID- 25075410
TI  - [Can transportation costs be claimed or not? Decision depends on the individual
      case].

PMID- 25075411
TI  - [What are the possibilities for private practitioners?].

PMID- 25075412
TI  - Osteoarthritis.

PMID- 25075413
TI  - Preoperative assessment of coagulation and bleeding risk.

PMID- 25075414
TI  - Intraoperative management of coagulation.

PMID- 25075415
TI  - Safeguarding integrity in research collaborations:possible strategies.

PMID- 25075416
TI  - The ward round: what it is and what it can be.

PMID- 25075417
TI  - Limb-girdle muscle weakness.

PMID- 25075418
TI  - Imaging in colorectal cancer.

PMID- 25075419
TI  - [Apathy in the structure of mental and neurological disorders of the old age].
AB  - The studies on apathy, a common phenomenon in psychiatry, are summarized. The
      definitions of this term suggested by different authors are presented. The
      difference between apathy as a symptom and apathy as a syndrome is described.
      Main pathogenetic mechanisms of the development and epidemiology of this
      disorder, the results on the differential diagnosis of apathy and depression in
      patients with neurological and mental diseases as well as methods of treatment
      are presented.

PMID- 25075420
TI  - [Anxiety-depressive disorders and stroke: possible etiopathogenetic
      correlations].
AB  - Anxiety-depressive disorders (ADD) and stroke are ranked among top ten diseases
      in the list of the World Health Organization.Comorbid cerebrovascular diseases
      and ADD worsen the clinical picture, each aggravating the progression and
      severity of the other. The detailed study of etiopathogenetic correlations
      between ADD and stroke can assist in the development of the unified
      pharmacological approach to their treatment.

PMID- 25075421
TI  - [Role of glycogen synthase kinase-3beta in the pathogenesis of mental disorders].
AB  - The literature review contains data about functions of glycogen synthase kinase
      313 (GSK-313) in the cell and its role in the functioning of the nervous tissue,
      an analysis of current research on the participation of GSK-313 in the
      pathogenesis of affective disorders and schizophrenia and effect of psychotropic
      drugs on the activity of the kinase.

PMID- 25075422
TI  - [Current aspects of rehabilitation of stroke patients].
AB  - Based on the review of literature, the key aspects of stroke rehabilitation
      (medical, physical, psychological, professional and social) were singled out.
      Main principles of medical aspects were defined as following: early
      rehabilitation, systemic and long term measures, their complicity and
      disciplinary, adequacy of rehabilitation measures and providing the conditions
      for the active participation of the patient and his/her close friends and
      relatives. Measures directed to motor, speech and cognitive function recovery are
      considered. In conclusion, attention is drawn to pharmacological drugs, in
      particular nicergoline (sermion).

PMID- 25075423
TI  - Characterization of a novel CYP2C9 mutation (1009C>A) detected in a warfarin
      sensitive patient.
AB  - Warfarin is the most frequently prescribed anticoagulant for the long-term
      treatment in the clinic. Recent studies have shown that polymorphic alleles
      within the CYP2C9, VKORC1, and CYP4F2 genes are related to the warfarin dosage
      requirement. In this study, a novel non-synonymous mutation (1009C>A) in CYP2C9
      was detected in a warfarin-hypersensitive patient, while the other two candidate
      genes were both found to be homozygous for the wild-type alleles. The newly
      identified point mutation results in an amino acid substitution at position 337
      of the CYP2C9 protein (P337T) and has been designated as the novel allele
      CYP2C9*58. When expressed in insect cell microsomes, the relative intrinsic
      clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite
      similar to those of the typical defective variant CYP2C9.3, whereas the clearance
      value of CYP2C9.58 for diclofenac was slightly higher than that of another
      typical defective variant CYP2C9.2. These data suggested that when compared with
      wild-type CYP2C9.1, the enzymatic activity of the novel allelic variant has been
      greatly reduced by the 1009C>A mutation. If patients carrying this allele take
      drugs metabolized by CYP2C9, their metabolic rate might be slower than that of
      wild-type allele carriers and thus much more attention should be paid to their
      clinical care.

PMID- 25075424
TI  - Cardioprotective effect of protocatechuic acid on myocardial ischemia/reperfusion
      injury.
AB  - Protocatechuic acid (PCA), a phenolic compound and one of the main metabolites of
      complex polyphenols, has been found to possess various biological activities, and
      it may have a potential in the treatment of ischemic heart diseases. This study
      explored the cardioprotective effect of PCA on myocardial ischemia/reperfusion
      (MI/R) injury and the underlying mechanisms. In an in vivo rat model of MI/R
      injury, myocardial infarct size, serum TNF-a level, and platelet aggregation were
      measured. In a primary neonatal rat cardiomyocyte model of hypoxia/ reoxygenation
      (H/R) injury, the apoptotic rate, expressions of cleaved caspase-3, and
      phosphorylated Akt were observed. We found that PCA significantly reduced
      myocardial infarct size, serum TNF-a level, and platelet aggregation. In vitro
      experiments revealed that PCA significantly inhibited the apoptotic rate and the
      expression of cleaved caspase-3, and it upregulated the expression of
      phosphorylated Akt in cardiomyocytes subjected to H/R injury. Our results suggest
      that PCA can provide a significant protection against MI/R injury, which may be
      at least partially attributed to its inhibitions against injury induced by MI/R
      including the inflammatory response, platelet aggregation, and cardiomyocytes
      apoptosis.

PMID- 25075426
TI  - Care in the air. How Vanderbilt LifeFlight trains its crews to take care from the
      hospital to the patient.

PMID- 25075425
TI  - 4',6-dihydroxy-4-methoxyisoaurone inhibits the HIF-1alpha pathway through
      inhibition of Akt/mTOR/p70S6K/4E-BP1 phosphorylation.
AB  - 4',6-Dihydroxy-4-methoxyisoaurone (ISOA) is an isoaurone compound isolated from
      Trichosanthes kirilowii seeds, which was identified as an inhibitor of tumor
      growth. However, the mechanism by which ISOA inhibits hypoxia-inducible factor-1
      (HIF-1)-mediated tumor growth is not fully understood. We here demonstrated the
      effect of ISOA on HIF-1 activation. ISOA showed a potent inhibitory activity
      against HIF-1 activation induced by hypoxia in various human cancer cell lines.
      This compound markedly decreased the hypoxia-induced accumulation of HIF-1a
      protein dose-dependently, whereas it did not affect the expressions of HIF-1b and
      topoisomerase-I (Topo-I). Further analysis revealed that the suppression of HIF
      1a accumulation by ISOA was closely correlated with strong dephosphorylation of
      Akt, mammalian target of rapamycin (mTOR), and its effectors ribosomal protein S6
      kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), a
      pathway known to regulate HIF-1a expression at the translational level.
      Furthermore, ISOA prevented hypoxia-induced expression of HIF-1 target genes and
      suppresses the invasiveness of tumor cells. Taken together, our results suggested
      that ISOA is an effective inhibitor of HIF-1 through targeting Akt/mTOR/p70S6K/4E
      BP1 pathway, thereby, providing new perspectives into the mechanism of its
      anticancer activity.

PMID- 25075428
TI  - Refined microdialysis method for protein biomarker sampling in acute brain injury
      in the neurointensive care setting.
AB  - There is growing interest in cerebral microdialysis (MD) for sampling of protein
      biomarkers in neurointensive care (NIC) patients. Published data point to
      inherent problems with this methodology including protein interaction and
      biofouling leading to unstable catheter performance. This study tested the in
      vivo performance of a refined MD method including catheter surface modification,
      for protein biomarker sampling in a clinically relevant porcine brain injury
      model. Seven pigs of both sexes (10-12 weeks old; 22.2-27.3 kg) were included.
      Mean arterial blood pressure, heart rate, intracranial pressure (ICP) and
      cerebral perfusion pressure was recorded during the stepwise elevation of
      intracranial pressure by inflation of an epidural balloon catheter with saline (1
      mL/20 min) until brain death. One naive MD catheter and one surface modified with
      Pluronic F-127 (10 mm membrane, 100 kDa molecular weight cutoff MD catheter) were
      inserted into the right frontal cortex and perfused with mock CSF with 3% Dextran
      500 at a flow rate of 1.0 MUL/min and 20 min sample collection. Naive catheters
      showed unstable fluid recovery, sensitive to ICP changes, which was significantly
      stabilized by surface modification. Three of seven naive catheters failed to
      deliver a stable fluid recovery. MD levels of glucose, lactate, pyruvate,
      glutamate, glycerol and urea measured enzymatically showed an expected gradual
      ischemic and cellular distress response to the intervention without differences
      between naive and surface modified catheters. The 17 most common proteins
      quantified by iTRAQ and nanoflow LC-MS/MS were used as biomarker models. These
      proteins showed a significantly more homogeneous response to the ICP intervention
      in surface modified compared to naive MD catheters with improved extraction
      efficiency for most of the proteins. The refined MD method appears to improve the
      accuracy and precision of protein biomarker sampling in the NIC setting. 

PMID- 25075430
TI  - New problems arising from old drugs: second-generation effects of acetaminophen.
AB  - Acetaminophen (APAP)/paracetamol is one of the most commonly used over-the
      counter drugs taken worldwide for treatment of pain and fever. Although
      considered as safe when taken in recommended doses not higher than 4 g/day, APAP
      overdose is currently the most important cause of acute liver failure (ALF). ALF
      may require liver transplantation and can be fatal. The reasons for APAP-related
      ALF are mostly intentional (suicidal) or unintentional overdose. However, results
      from large scale epidemiological studies provide increasing evidence for second
      generation effects of APAP, even when taken in pharmacological doses. Most
      strikingly, APAP medication during pregnancy has been associated with health
      problems including neurodevelopmental and behavioral disorders such as attention
      deficit hyperactivity disorder and increase in the risk of wheezing and incidence
      of asthma among offspring. This article reviews the epidemiological findings and
      aims to shed light into the molecular and cellular mechanisms responsible for
      APAP-mediated prenatal risk for asthma. 

PMID- 25075429
TI  - Assessing the impact of typeface design in a text-rich automotive user interface.
AB  - Text-rich driver-vehicle interfaces are increasingly common in new vehicles, yet
      the effects of different typeface characteristics on task performance in this
      brief off-road based glance context remains sparsely examined. Subjects completed
      menu selection tasks while in a driving simulator. Menu text was set either in a
      'humanist' or 'square grotesque' typeface. Among men, use of the humanist
      typeface resulted in a 10.6% reduction in total glance time as compared to the
      square grotesque typeface. Total response time and number of glances showed
      similar reductions. The impact of typeface was either more modest or not apparent
      for women. Error rates for both males and females were 3.1% lower for the
      humanist typeface. This research suggests that optimised typefaces may mitigate
      some interface demands. Future work will need to assess whether other typeface
      characteristics can be optimised to further reduce demand, improve legibility,
      increase usability and help meet new governmental distraction guidelines.
      Practitioner Summary: Text-rich in-vehicle interfaces are increasingly common,
      but the effects of typeface on task performance remain sparsely studied. We show
      that among male drivers, menu selection tasks are completed with 10.6% less
      visual glance time when text is displayed in a 'humanist' typeface, as compared
      to a 'square grotesque'. 

PMID- 25075431
TI  - An interrupted vinylogous iso-Nazarov reaction: cycloisomerization of conjugated
      trienones to cyclopenta[b]furan derivatives.
AB  - Iron(III) chloride-catalyzed cyclopentannulation of pi-conjugated 1,3-dicarbonyl
      compounds is described. An interrupted vinylogous iso-Nazarov reaction of
      trienones was established in which cyclopenta[b]furan derivatives are obtained as
      single diastereomers. 

PMID- 25075432
TI  - Effects of dietary supplementation with creatine monohydrate during the finishing
      period on growth performance, carcass traits, meat quality and muscle glycolytic
      potential of broilers subjected to transport stress.
AB  - A total of 320 male Arbor Acres broiler chickens (28 days old) were randomly
      allotted to one of the three experimental diets supplemented with 0 (160 birds),
      600 (80 birds) or 1200 mg/kg (80 birds) creatine monohydrate (CMH) for 14 days.
      On the morning of 42 day, after an 8-h fast, the birds of CMH-free group were
      divided into two equal groups, and all birds of these four groups were
      transported according to the follow protocol: 0.75-h transport without CMH
      supplementation (as a lower stress control group), 3-h transport without CMH
      supplementation, 3-h transport with 600 or 1200 mg/kg CMH supplementation. Each
      treatment group was composed of 8 replicates with 10 birds each. The results
      showed that supplementation of CMH for 14 days before slaughter did not affect
      the overall growth performance and carcass traits of stressed broilers (P>0.05).
      A 3-h transport decreased plasma glucose concentration, elevated plasma
      corticosterone concentration, increased bird live weight loss, breakdown of
      muscle glycogen, as well as the accumulation of muscle lactate (P<0.05), which
      induced some detrimental changes to breast meat quality (lower ultimate pH and
      higher drip loss, P<0.05). Nevertheless, supplementation of 1200 mg/kg CMH
      reduced chicken weight loss, decreased the contents of lactate and glycolytic
      potential in pectoralis major of 3-h transported broilers (P<0.05), which is
      beneficial to maintain breast meat quality by reducing the drip loss (P<0.05).
      These findings suggest that the reduction of muscle glycolysis is probably the
      reason for maintainance of meat quality by supplementation of CMH in transported
      broilers. 

PMID- 25075433
TI  - Intracellular antioxidant detoxifying effects of diosmetin on 2,2-azobis(2
      amidinopropane) dihydrochloride (AAPH)-induced oxidative stress through
      inhibition of reactive oxygen species generation.
AB  - The intracellular antioxidant activities of diosmetin were evaluated by cellular
      antioxidant activity (CAA) assay, 2,2-azobis(2-amidinopropane) dihydrochloride
      (AAPH)-induced erythrocyte hemolysis assay and cupric chloride (CuCl2)-induced
      plasma oxidation assay. The results showed that diosmetin exhibits strong
      cellular antioxidant activity (EC50 = 7.98 MUmol, CAA value = 58 MUmol QE/100
      MUmol). It was also found that diosmetin treatment could effectively attenuate
      AAPH-induced erythrocyte hemolysis (91.0% inhibition at 100 MUg/mL) and CuCl2
      induced plasma oxidation through inhibition of intracellular reactive oxygen
      species (ROS) generation. Diosmetin could significantly restore AAPH-induced
      increase of intracelluar antioxidant enzyme (SOD, GPx, and CAT) activities to
      normal levels, as well as inhibit intracellular malondialdehyde (MDA) formation.
      Thus, the intracellular antioxidant detoxifying mechanism of diosmetin is
      associated with both nonenzymatic and enzymatic defense systems. 

PMID- 25075434
TI  - Alkynes as allylmetal equivalents in redox-triggered C-C couplings to primary
      alcohols: (Z)-homoallylic alcohols via ruthenium-catalyzed propargyl C-H
      oxidative addition.
AB  - The cationic ruthenium catalyst generated upon the acid-base reaction of
      H2Ru(CO)(PPh3)3 and 2,4,6-(2-Pr)3PhSO3H promotes the redox-triggered C-C coupling
      of 2-alkynes and primary alcohols to form (Z)-homoallylic alcohols with good to
      complete control of olefin geometry. Deuterium labeling studies, which reveal
      roughly equal isotopic compositions at the allylic and distal vinylic positions,
      along with other data, corroborate a catalytic mechanism involving ruthenium(0)
      mediated allene-aldehyde oxidative coupling to form a transient oxaruthenacycle,
      an event that ultimately defines (Z)-olefin stereochemistry. 

PMID- 25075435
TI  - PRKCZ methylation is associated with sunlight exposure in a North American but
      not a Mediterranean population.
AB  - Sunlight exposure has been shown to alter DNA methylation patterns across several
      human cell-types, including T-lymphocytes. Since epigenetic changes establish
      gene expression profiles, changes in DNA methylation induced by sunlight exposure
      warrant investigation. The purpose of this study was to assess the effects of
      sunlight exposure on CD4+ T-cell methylation patterns on an epigenome-wide scale
      in a North American population of European origin (n=991). In addition, we
      investigated the genetic contribution to epigenetic variation (methylQTL). We
      used linear regression to test the associations between methylation scores at
      461,281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by
      a genome-wide association analysis (methylQTL) to test for associations between
      methylation at the top CpG locus and common genetic variants, assuming an
      additive genetic model. We observed an epigenome-wide significant association
      between sunlight exposure and methylation status at cg26930596 (p=9.2*10(-8)), a
      CpG site located in protein kinase C zeta (PRKCZ), a gene previously shown to be
      entrained by light. MethylQTL analysis resulted in significant associations
      between cg26930596 and two intergenic single nucleotide polymorphisms on
      chromosome 3, rs4574216 (p=1.5*10(-10)) and rs4405858 (p=1.9*10(-9)). These
      common genetic variants reside downstream of WWTR1, a transcriptional co
      activator of PRKCZ. Associations observed in the North American population,
      however, did not replicate in an independent Mediterranean cohort. Our
      preliminary results support the role of sunlight exposure in epigenetic
      processes, and lay the groundwork for future studies of the molecular link
      between sunlight and physiologic processes such as tumorigenesis and metabolism.

PMID- 25075436
TI  - Opposites don't attract: high spouse concordance for dietary supplement use in
      the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk)
      cohort study.
AB  - OBJECTIVE: Dietary supplements are commonly consumed but may not be beneficial
      for everyone. It is known that supplement users have healthy behaviour
      characteristics but until now concordance between spouses living in the same
      household has not been investigated and concordance may be an important
      behavioural determinant. DESIGN: Prospective cohort study, cross-sectional data
      analysis. SETTING: European Prospective Investigation into Cancer in Norfolk
      (EPIC-Norfolk) in the UK, recruitment between 1993 and 1998. SUBJECTS: Married
      (or living as married) participants sharing a household, who attended a health
      examination and completed a 7 d diet diary were included in the analysis (n 11
      060). The age range was 39-79 years. RESULTS: Nearly 75 % of the households in
      EPIC-Norfolk were concordant in their supplement use, with 46.7 % not using
      supplements and 27.0 % using supplements. Concordance increased with age; the
      percentage of concordant couples varied less by other sociodemographic
      characteristics. Participants who had a spouse who used a supplement were nearly
      nine times more likely to use a supplement (unadjusted). Depending on
      participants' sex and type of supplement used, odds ratios for 'supplement use by
      spouse' in the prediction of participants' supplement use varied between 6.2 and
      11.7 adjusted for participants' age, smoking status, BMI, social class, education
      level and physical activity. CONCLUSIONS: 'Supplement use by spouse' is an
      independent and the strongest predictor of participants' supplement use. This
      phenomenon can be useful in the design of studies and health interventions; or
      when assessing risk of excessive intake from dietary supplements.

PMID- 25075437
TI  - Our journal is now 50 years old part 1: how it all started.

PMID- 25075438
TI  - A normative study of total scores of the CERAD neuropsychological assessment
      battery in an educationally diverse elderly population.
AB  - BACKGROUND: This study aimed to investigate the influences of age, education, and
      gender on the two total scores (TS-I and TS-II) of the Consortium to Establish a
      Registry for Alzheimer's Disease Neuropsychological assessment battery (CERAD-NP)
      and to provide normative information based on an analysis for a large number of
      elderly persons with a wide range of educational levels. METHODS: In the study,
      1,987 community-dwelling healthy volunteers (620 males and 1,367 females; 50-90
      years of age; and zero to 25 years of education) were included. People with
      serious neurological, medical, and psychiatric disorders (including dementia)
      were excluded. All participants underwent the CERAD-NP assessment. TS-I was
      generated by summing raw scores from the CERAD-NP subtests, excluding Mini-Mental
      State Examination and Constructional Praxis (CP) recall subtests. TS-II was
      calculated by adding CP recall score to TS-I. RESULTS: Both TS-I and TS-II were
      significantly influenced by demographic variables. Education accounted for the
      greatest proportion of score variance. Interaction effect between age and gender
      was found. Based on the results obtained, normative data of the CERAD-NP total
      scores were stratified by age (six overlapping tables), education (four strata),
      and gender. CONCLUSIONS: The normative information will be very useful for better
      interpretation of the CERAD-NP total scores in various clinical and research
      settings and for comparing individuals' performance of the battery across
      countries.

PMID- 25075439
TI  - Needs, expectations, and concerns of medical students regarding end-of-life
      issues before the introduction of a mandatory undergraduate palliative care
      curriculum.
AB  - BACKGROUND: In the past, implementation of effective palliative care curricula
      has emerged as a priority in medical education. In order to gain insight into
      medical students' needs and expectations, we conducted a survey before mandatory
      palliative care education was introduced in our faculty. METHODS: Seven hundred
      nine students answered a questionnaire mainly consisting of numeric rating scales
      (0-10). RESULTS: Participants attributed a high importance to palliative care for
      their future professional life (mean, 7.51 +/- 2.2). For most students, symptom
      control was crucial (7.72 +/- 2.2). However, even higher importance was assigned
      to ethical and legal issues (8.16 +/- 1.9). "Self-reflection regarding their own
      role as a physician caring for the terminally ill along with psychological
      support" was also regarded as highly important (7.25 +/- 2.4). Most students were
      moderately concerned at the prospect of being confronted with suffering and death
      (5.13 +/- 2.4). This emotional distress was rated significantly higher by female
      students (5.4 +/- 2.4 versus 4.6 +/- 2.4; p < 0.001). Seventeen percent of all
      students rated their distress as being 7 of 10 or higher, which indicates a
      considerable psychological strain in terms of dealing with end-of-life issues in
      the future. Professional or personal experience with terminally ill persons
      lowered these anxieties significantly (4.99 +/- 2.34 versus 5.47 +/- 2.5, p <
      0.05). CONCLUSIONS: Medical students stated a remarkably high interest in
      learning palliative care competencies. Responding to their specific concerns and
      needs-especially with regard to the acquisition of emotional coping skills-may be
      key for the development of successful palliative care curricula.

PMID- 25075440
TI  - Autophagy-related gene expression analysis of wild-type and atg5 gene knockout
      mouse embryonic fibroblast cells treated with polyethylenimine.
AB  - The molecular mechanisms of autophagy in polyethylenimine (PEI)-treated cells are
      not well understood because of the use of nonspecific autophagy inhibitors. Here,
      we applied autophagy-related gene expression analysis to pinpoint the molecular
      mechanisms of autophagy in PEI-treated wild-type and atg5 gene knockout (atg5(-/
      )) mouse embryonic fibroblast (MEF) cells. It was demonstrated that the majority
      of induced genes are downregulated in wild-type and atg5(-/-) MEF cells,
      indicating that autophagy exhibits a trend toward downregulation after treatment
      with PEI. In addition to regulating genes encoding autophagy machinery
      components, genes related to coregulation of autophagy and apoptosis were induced
      in wild-type and atg5(-/-) cells treated with PEI. These data indicate that
      autophagy and apoptosis are closely related in the PEI-induced mechanism of cell
      death. In the absence of autophagy, the regulation of apoptosis was enhanced in
      atg5(-/-) MEF cells treated with PEI, indicating that inhibition of autophagy may
      lead to higher levels of apoptosis. Our study may provide deeper insight into the
      molecular mechanisms of cell death caused by PEI. 

PMID- 25075442
TI  - Deviatoric stress-driven fusion of nanoparticle superlattices.
AB  - We model the mechanical response of alkanethiol-passivated gold nanoparticle
      superlattice (supercrystal) at ambient and elevated pressures using large-scale
      molecular dynamics simulation. Because of the important roles of soft organic
      ligands in mechanical response, the supercrystals exhibit entropic
      viscoelasticity during compression at ambient pressure. Applying a hydrostatic
      pressure of several hundred megapascals on the superlattice, combined with a
      critical deviatoric stress of the same order along the [110] direction of the
      face-centered-cubic supercrystal, can drive the room-temperature sintering
      ("fusion") of gold nanoparticles into ordered gold nanowire arrays. We discuss
      the molecular-level mechanism of such phenomena and map out a nonequilibrium
      stress-driven processing diagram, which reveals a region in stress space where
      fusion of nanoparticles can occur, instead of other competing plasticity or phase
      transformation processes in the supercrystal. We further demonstrate that, for
      silver-gold (Ag-Au) binary nanoparticle superlattices in sodium chloride-type
      superstructure, stress-driven fusion along the [100] direction leads to the
      ordered formation of Ag-Au multijunction nanowire arrays. 

PMID- 25075443
TI  - Retrospective Validation of a Protocol to Limit Unnecessary Transport of Assisted
      living Residents Who Fall.
AB  - Abstract Objective. Emergency medical services (EMS) often transports patients
      who suffer simple falls in assisted-living facilities (ALFs). An EMS "falls
      protocol" could avoid unnecessary transport for many of these patients, while
      ensuring that patients with time-sensitive conditions are transported. Our
      objective was to retrospectively validate an EMS protocol to assist decision
      making regarding the transport of ALF patients with simple falls. Methods. We
      conducted a retrospective cohort study of patients transported to the emergency
      department from July 2010 to June 2011 for a chief complaint of "fall" within a
      subset of ALFs served by a specific primary care group in our urban EMS system
      (population 900,000). The primary outcome, "time-sensitive intervention" (TSI),
      was met by patients who had wound repair or fracture, admission to the ICU, OR,
      or cardiac cath lab, death during hospitalization, or readmission within 48
      hours. EMS and primary care physicians developed an EMS protocol, a priori and by
      consensus, to require transport for patients needing TSI. The protocol utilizes
      screening criteria, including history and exam findings, to recommend transport
      versus nontransport with close primary care follow-up. The EMS protocol was
      retrospectively applied to determine which patients required transport. Protocol
      performance was estimated using sensitivity, specificity, and negative predictive
      value (NPV). Results. Of 653 patients transported across 30 facilities, 644 had
      sufficient data. Of these, 197 (31%) met the primary outcome. Most patients who
      required TSI had fracture (73) or wound repair (92). The EMS protocol identified
      190 patients requiring TSI, for a sensitivity of 96% (95% CI: 93-98%),
      specificity of 54% (95% CI: 50-59%), and NPV of 97% (95% CI: 94-99%). Of 7
      patients with false negatives, 3 were readmitted (and redischarged) after another
      fall, 3 sustained hip fractures that were surgically repaired, and 1 had a lumbar
      compression fracture and was discharged. Conclusions. In this cohort, two-thirds
      of patients with falls in ALFs did not require TSI. An EMS protocol may have
      sufficient sensitivity to safely allow for nontransport of these patients with
      falls in ALFs. Prospective validation of the protocol is necessary to test this
      hypothesis.

PMID- 25075441
TI  - Genomic editing tools to model human diseases with isogenic pluripotent stem
      cells.
AB  - Patient-specific induced pluripotent stem cells (iPSCs) are considered a
      versatile resource in the field of biomedicine. As iPSCs are generated on an
      individual basis, iPSCs may be the optimal cellular material to use for disease
      modeling, drug discovery, and the development of patient-specific cellular
      therapies. Recently, to gain an in-depth understanding of human pathologies,
      patient-specific iPSCs have been used to model human diseases with some iPSC
      derived cells recapitulating pathological phenotypes in vitro. However, complex
      multigenic diseases generally have not resulted in concise conclusions regarding
      the underlying mechanisms of disease, in large part due to genetic variations
      between disease-state and control iPSCs. To circumvent this, the use of genomic
      editing tools to generate perfect isogenic controls is gaining momentum. To date,
      DNA binding domain-based zinc finger nucleases and transcription activator-like
      effector nucleases have been utilized to create genetically defined conditions in
      patient-specific iPSCs, with some examples leading to the successful
      identification of novel mechanisms of disease. As the feasibility and utility of
      genomic editing tools in iPSCs improve, along with the introduction of the
      clustered regularly interspaced short palindromic repeat system, understanding
      the features and limitations of genomic editing tools and their applications to
      iPSC technology is critical to expending the field of human disease modeling. 

PMID- 25075444
TI  - Photoinduced electron transfer in donor-acceptor complexes of ethylene with
      molecular and atomic iodine.
AB  - Building upon our recent studies of radical addition pathways following
      excitation of the I2 chromophore in the donor-acceptor complex of ethylene and I2
      (C2H4...I2), in this article, we extend our studies to examine photoinduced
      electron transfer. Thus, irradiation into the intense charge-transfer band of the
      complex (lambdamax = 247 nm) gave rise to a band at 366 nm that is assigned to
      the bridged ethylene-I radical complex on the basis of our prior work. The
      formation of the radical complex is explained by a mechanism that involves rapid
      back electron transfer leading to I-I bond fission. Excitation into the charge
      transfer band of the radical complex led to regeneration of the parent complex
      and the formation of the final photoproduct, anti- and gauche-1,2-diiodoethane,
      which confirms that the reaction proceeds ultimately by a radical addition
      mechanism. This finding is contrasted with our previous study of the C2H4...Br2
      complex, where CT excitation led to only one product, anti-1,2-dibromoethane, a
      result explained by a single electron-transfer mechanism proceeding via a bridged
      bromonium ion intermediate. For the I2 complex, the breakup of the photolytically
      generated I2(-*) anion radical is apparently sufficiently slow to render it
      uncompetitive with back electron transfer. Finally, we report a detailed
      computational examination of the parent and radical complexes of both bromine and
      iodine, using high-level single- and multireference methods, which provide
      insight into the different behaviors of the charge-transfer states of the two
      radicals and the role of spin-orbit coupling. 

PMID- 25075445
TI  - Regulation of gene expression in the protozoan parasite Entamoeba invadens:
      identification of core promoter elements and promoters with stage-specific
      expression patterns.
AB  - Developmental switching between life-cycle stages is a common feature among many
      pathogenic organisms. Entamoeba histolytica is an important human pathogen and is
      a leading parasitic cause of death globally. During its life cycle, Entamoeba
      converts between cysts (essential for disease transmission) and trophozoites
      (responsible for tissue invasion). Despite being central to its biology, the
      triggers that are involved in the developmental pathways of this parasite are not
      well understood. In order to define the transcriptional network associated with
      stage conversion we used Entamoeba invadens which serves as a model system for
      Entamoeba developmental biology, and performed RNA sequencing at different
      developmental time points. In this study RNA-Seq data was utilised to define
      basal transcriptional control elements as well as to identify promoters which
      regulate stage-specific gene expression patterns. We discovered that the 5' and
      3' untranslated regions of E. invadens genes are short, a median of 20
      nucleotides (nt) and 26 nt respectively. Bioinformatics analysis of DNA sequences
      proximate to the start and stop codons identified two conserved motifs: (i) E.
      invadens Core Promoter Motif - GAAC-Like (EiCPM-GL) (GAACTACAAA), and (ii) E.
      invadens 3'-U-Rich Motif (Ei3'-URM) (TTTGTT) in the 5' and 3' flanking regions,
      respectively. Electrophoretic mobility shift assays demonstrated that both motifs
      specifically bind nuclear protein(s) from E. invadens trophozoites. Additionally,
      we identified select genes with stage-specific expression patterns and analysed
      the ability of each gene promoter to drive a luciferase reporter gene during the
      developmental cycle. This approach confirmed three trophozoite-specific, four
      encystation-specific and two excystation-specific promoters. This work lays the
      framework for use of stage-specific promoters to express proteins of interest in
      a particular life-cycle stage, adding to the molecular toolbox for genetic
      manipulation of E. invadens and allowing further dissection of factors
      controlling Entamoeba developmental biology. 

PMID- 25075446
TI  - Lymphadenopathy in a Series of Egyptian Pediatric Patients and the Role of
      Pathology in the Diagnostic Workup.
AB  - Assessment of lymphadenopathy in children represents a diagnostic challenge
      because of the extensive differential diagnoses including reactive and malignant
      conditions. Knowledge of the etiologic pattern of lymphadenopathy in a given
      geographical region is essential for making a confident diagnosis or suspecting a
      disease. Hence, the present study was carried out to identify different
      etiologies of lymphadenopathy in children in our region, and assess parameters
      commonly associated with malignancy, with an emphasis on the role of pathology in
      the diagnostic workup. One hundred and twenty patients aged one month to 18 years
      were included in the study. They were sorted into neoplastic and non-neoplastic
      (Infectious and non-infectious). In only 56 patients, biopsy, whether fine needle
      aspiration cytology (FNAC), core needle or excision biopsy, was essential to
      reach the final diagnosis. Sensitivity of FNAC in the differentiation between
      neoplastic and non-neoplastic lymphadenopathy was 92.3%, specificity 90.0%, with
      a diagnostic accuracy of 91.3%. We concluded that malignancy should be suspected
      in the following conditions: presence of abdominal or multiple symptoms, symptoms
      duration of 1-6 months, generalized lymphadenopathy, multiple groups of lymph
      node (LN) involved, LN size > 2 cm, amalgamated, hard, fixed and non-tender LNs,
      certain abnormal CBC findings, blast cells in blood film and elevated LDH level.
      In such cases, LN biopsy is highly recommended. A final diagnosis was achieved
      after integrating information from history and clinical findings with those of
      the laboratory, radiological, pathological and microbiological findings.
      Accordingly, an algorithm for primary diagnostic evaluation of children with
      lymphadenopathy is suggested.

PMID- 25075448
TI  - Association between interleukin-27 gene polymorphisms and susceptibility to
      allergic rhinitis.
AB  - OBJECTIVES: Allergic rhinitis (AR) is an inflammatory disorder of the upper
      airway. Interleukin-27 (IL-27), a novel IL-12 family member, has recently been
      reported to play a role in some immune-related disorders. This study was
      performed to evaluate the potential association of IL-27 polymorphisms with AR in
      a Chinese Han population. DESIGN AND METHODS: A case-control study was performed
      in 445 Chinese AR patients and 691 healthy controls. Three SNPs in the IL-27p28
      gene, including rs153109, rs17855750 and rs181206, were detected using a
      polymerase chain reaction-restriction fragment length polymorphism assay (PCR
      RFLP). RESULTS: A significantly increased prevalence of the rs153109 TT genotype
      and the T allele was found in AR patients, while a decreased prevalence of the CT
      and CC genotypes and the C allele was found. For rs153109, the TT genotype and
      the T allele were significantly associated with the risk of AR, but the CT and CC
      genotypes and the C allele decreased the risk of AR; for rs17855750, the TT
      genotype and T allele were risk factors for AR, and the GT genotype and G allele
      provided protection. TTT and TTC haplotypes in the IL-27p28 gene were positively
      correlated with AR, while CGT, CTC and CTT haplotypes were associated with a
      significantly decreased risk of AR. CONCLUSION: This study indicates that IL
      27p28 polymorphisms rs153109 and rs17855750 are likely involved in AR
      susceptibility, making them potentially useful genetic biomarkers for AR
      susceptibility in the Chinese Han population.

PMID- 25075447
TI  - Tunable control of polyproline helix (PPII) structure via aromatic electronic
      effects: an electronic switch of polyproline helix.
AB  - Aromatic rings exhibit defined interactions via the unique aromatic pi face.
      Aromatic amino acids interact favorably with proline residues via both the
      hydrophobic effect and aromatic-proline interactions, C-H/pi interactions between
      the aromatic pi face and proline ring C-H bonds. The canonical aromatic amino
      acids Trp, Tyr, and Phe strongly disfavor a polyproline helix (PPII) when they
      are present in proline-rich sequences because of the large populations of cis
      amide bonds induced by favorable aromatic-proline interactions (aromatic-cis
      proline and proline-cis-proline-aromatic interactions). We demonstrate the
      ability to tune polyproline helix conformation and cis-trans isomerism in proline
      rich sequences using aromatic electronic effects. Electron-rich aromatic residues
      strongly disfavor polyproline helix and exhibit large populations of cis amide
      bonds, while electron-poor aromatic residues exhibit small populations of cis
      amide bonds and favor polyproline helix. 4-Aminophenylalanine is a pH-dependent
      electronic switch of polyproline helix, with cis amide bonds favored as the
      electron-donating amine, but trans amide bonds and polyproline helix preferred as
      the electron-withdrawing ammonium. Peptides with block proline-aromatic
      PPXPPXPPXPP sequences exhibited electronically switchable pH-dependent
      structures. Electron-poor aromatic amino acids provide special capabilities to
      integrate aromatic residues into polyproline helices and to serve as the basis of
      aromatic electronic switches to change structure. 

PMID- 25075449
TI  - Determination of the internal morphology of nanostructures patterned by directed
      self assembly.
AB  - The directed self-assembly (DSA) of block copolymers (BCP) is an emerging
      resolution enhancement tool that can multiply or subdivide the pitch of a
      lithographically defined chemical or topological pattern and is a resolution
      enhancement candidate to augment conventional lithography for patterning sub-20
      nm features. Continuing the development of this technology will require an
      improved understanding of the polymer physics involved as well as experimental
      confirmation of the simulations used to guide the design process. Both of these
      endeavors would be greatly facilitated by a metrology, which is capable of
      probing the internal morphology of a DSA film. We have developed a new
      measurement technique, resonant critical-dimension small-angle X-ray scattering
      (res-CDSAXS), to evaluate the 3D buried features inside the film. This is an X
      ray scattering measurement where the sample angle is varied to probe the 3D
      structure of the film, while resonant soft X-rays are used to enhance the
      scattering contrast. By measuring the same sample with both res-CDSAXS and
      traditional CDSAXS (with hard X-rays), we are able to demonstrate the dramatic
      improvement in scattering obtained through the use of resonant soft X-rays.
      Analysis of the reciprocal space map constructed from the res-CDSAXS measurements
      allowed us to reconstruct the complex buried features in DSA BCP films. We
      studied a series of DSA BCP films with varying template widths, and the internal
      morphologies for these samples were compared to the results of single chain in
      mean-field simulations. The measurements revealed a range of morphologies that
      occur with changing template width, including results that suggest the presence
      of mixed morphologies composed of both whole and necking lamella. The development
      of res-CDSAXS will enable a better understanding of the fundamental physics
      behind the formation of buried features in DSA BCP films. 

PMID- 25075450
TI  - Polycystic kidney disease in neonate with acrorenal mandibular syndrome.

PMID- 25075451
TI  - Ocular anomalies in Rubinstein-Taybi syndrome: a further case report and review
      of the literature.

PMID- 25075452
TI  - Familial amelia as reported by Michaud et al. (OMIM-601360): one more patient
      endorsing the phenotype.

PMID- 25075453
TI  - Novel reassortant influenza A(H5N8) viruses in domestic ducks, eastern China.
AB  - Domestic ducks are natural reservoirs of avian influenza viruses and serve as
      reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8)
      viruses from domestic ducks in eastern China, sequenced their genomes, and tested
      their pathogenicity in chickens and mice. Circulation of these viruses may pose
      health risks for humans. 

PMID- 25075454
TI  - Factors associated with empyema in children with community acquired pneumonia.
AB  - AIM: Empyema is a potential complication of community acquired pneumonia but
      factors predicting this complication are lacking. METHODS: A retrospective study
      of all previously healthy pediatric patients admitted between January 2007 and
      July 2009 with CAP. Patients with non-lobar pneumonia, RSV bronchiolitis,
      underlying chronic disease, or hospital-acquired pneumonia were excluded.
      Preadmission, clinical characteristics on admission, and outcome were compared
      between patients with and without empyema. Management strategies in patients with
      empyema were also compared. RESULTS: Overall 356 patients were included. Median
      age was 3.8 +/- 3.54 years and 60.7% were males. A total of 43 patients (12%)
      were diagnosed with empyema. The development of empyema was independently
      associated, on multivariate analysis, with older age, female gender and
      antibiotic therapy prior to admission, and with dyspnea, thrombocytopenia and
      involvement of more than one lobe on chest radiograph on admission. Patients who
      developed empyema had a longer and more complicated course. Hypoxemia on
      admission was significantly less frequent in patients with empyema who were
      treated with antibiotic therapy alone, compared to those treated with chest tube
      or video-assisted thoracoscopic surgery. CONCLUSION: Early identification of
      dyspnea and thrombocytopenia in patients with community acquired pneumonia could
      alert physicians on the potential development of empyema. Antibiotic therapy
      alone may be sufficient in patients with empyema who are mildly hypoxemic on
      admission.

PMID- 25075455
TI  - The nutritional composition and anti-hypertensive activity on spontaneously
      hypertensive rats of sipuncula Phascolosoma esculenta.
AB  - Recent studies have investigated anti-hypertensive peptides derived from natural
      food products. In this work, we focus on Phascolosoma esculenta as a resource of
      anti-hypertensive peptides, which is also a seafood with high nutritive value.
      Compared with FAO/WHO requirements, P. esculenta was confirmed to contain high
      contents of amino acids and minerals. To investigate the anti-hypertensive
      activity of P. esculenta, water-soluble and insoluble proteins were extracted and
      hydrolysed by pepsin and trypsin, respectively. The hydrolysates of water-soluble
      proteins derived by pepsin and pepsin-trypsin exhibited angiotensin-converting
      enzyme (ACE) inhibitory activity with IC50 values of 0.67 and 0.24 mg ml(-1),
      respectively, and those of water-insoluble proteins presented IC50 values of 0.4
      and 0.1 mg ml(-1), respectively. Experiments on 'spontaneously hypertensive rats'
      (SHRs) were carried out to test the anti-hypertension activity in vivo, which
      confirmed that the hydrolysates played a significant role in reducing both
      diastolic blood pressure (DBP) and systolic blood pressure (SBP). Consistently,
      the in vivo anti-hypertensive activity of the hydrolysis products of pepsin and
      trypsin used together was also higher than that by using pepsin hydrolysis
      products alone. As stated in both sets of results, we believe that P. esculenta
      is an excellent resource of antihypertensive peptides and warrants further
      investigation. 

PMID- 25075456
TI  - Ultrasound-guided interventional procedures in pain medicine: a review of
      anatomy, sonoanatomy, and procedures. Part V: knee joint.
AB  - Ultrasound-guided injection in pain medicine is emerging as a popular technique
      for pain intervention. It can be applied to the intra-articular injection of the
      knee joint. The first objective of this review was to describe and summarize the
      anatomy and sonoanatomy of the knee and associated structures relevant for intra
      articular injection. The second objective was to examine the feasibility,
      accuracy, and effectiveness of injections as well as injection techniques. 

PMID- 25075457
TI  - Fentanyl overdose caused by malfunction of SynchroMed II intrathecal pump: two
      case reports.
AB  - OBJECTIVE: Intrathecal drug delivery systems (intrathecal pumps) are used to
      treat patients with chronic refractory pain syndromes and spasticity. The
      objective of our case report was to demonstrate that intrathecal pump malfunction
      can lead to intrathecal overdosing of drugs. CASE REPORT: We present 2 cases of
      intrathecal pump malfunction leading to overinfusion. The first case concerns a
      patient with an intrathecal pump that was implanted almost 5 years before the
      reported incident. During a refill procedure, 12.5 mL was aspirated instead of
      the expected 21.8 mL. Analysis of the pump revealed that the pump was
      overinfusing. The second case concerns a patient with an intrathecal pump that
      was implanted more than 5 years before the reported incident. Ten hours after a
      regular refill of the pump, she was found in a comatose state, and when the
      intrathecal pump was emptied, only 16 mL was aspirated instead of the 19.6 mL
      expected. Analysis of the pump revealed that the inner tubing was not running
      smoothly over the roller arms, possibly causing spurts, which could have caused
      an overinfusion. CONCLUSIONS: We present 2 cases of intrathecal pump malfunction,
      which most likely led to overinfusion of fentanyl intrathecally. To reduce the
      risk of this complication, particular attention should be paid to drug reservoir
      volume discrepancies and overdose symptoms reported by patients.

PMID- 25075458
TI  - Photocarrier recombination dynamics in perovskite CH3NH3PbI3 for solar cell
      applications.
AB  - Using time-resolved photoluminescence and transient absorption measurements at
      room temperature, we report excitation-intensity-dependent photocarrier
      recombination processes in thin films made from the organo-metal halide
      perovskite semiconductor CH3NH3PbI3 for solar-cell applications. The photocarrier
      dynamics are well described by a simple rate equation including single-carrier
      trapping and electron-hole radiative recombination. This result provides clear
      evidence that the free-carrier model is better than the exciton model for
      interpreting the optical properties of CH3NH3PbI3. The observed large two-carrier
      recombination rate suggests the promising potential of perovskite semiconductors
      for optoelectronic device applications. Our findings provide the information
      about the dynamical behaviors of photoexcited carriers that is needed for
      developing high-efficiency perovskite solar cells. 

PMID- 25075459
TI  - Theoretical study on the initial stage of a magnesium battery based on a V2O5
      cathode.
AB  - Several first-principles calculations based on density functional theory have
      been carried out looking at the key issues of a magnesium battery with a V2O5
      cathode. This kind of magnesium battery was reported by D. Aurbach's group in
      2013. Our theoretical studies provide explanations for the experimental findings
      such as higher voltage, slow ion diffusivity and the decrease of the
      crystallinity. The calculated open circuit voltage of a magnesium battery with a
      V2O5 cathode is 3.06 V, which is 0.22 V higher than a lithium battery with the
      same cathode. Electronic band structure calculations suggest that higher
      electronic conductivity must be expected in a magnesium battery. Elastic
      constants are obtained, which give information on the stability of the
      magnesiated cathode. Furthermore, we have also calculated the diffusion barriers
      of Li and Mg ions in the cathode using the nudged elastic band method. The
      hopping barrier of Mg ions is 1.26 eV, which is much higher than that of Li ions
      (0.35 eV). The obtained minimum energy paths show the different hopping processes
      in the lithium and magnesium batteries, which can explain the phenomenon of slow
      diffusion in experiments. The possible transition pathway between the alpha and
      delta phases is analyzed for the first time, which gives an explanation for the
      reversibility of Mg ions in the V2O5 cathode. 

PMID- 25075460
TI  - Immune responses during cutaneous and visceral leishmaniasis.
AB  - SUMMARY Leishmania are protozoan parasites spread by a sandfly insect vector and
      causing a spectrum of diseases collectively known as leishmaniasis. The disease
      is a significant health problem in many parts of the world, resulting in an
      estimated 1.3 million new cases and 30 000 deaths annually. Current treatment is
      based on chemotherapy, which is difficult to administer, expensive and becoming
      ineffective in several endemic regions. To date there is no vaccine against
      leishmaniasis, although extensive evidence from studies in animal models
      indicates that solid protection can be achieved upon immunization. This review
      focuses on immune responses to Leishmania in both cutaneous and visceral forms of
      the disease, pointing to the complexity of the immune response and to a range of
      evasive mechanisms utilized by the parasite to bypass those responses. The
      amalgam of innate and acquired immunity combined with the paucity of data on the
      human immune response is one of the major problems currently hampering vaccine
      development and implementation.

PMID- 25075461
TI  - Sheet resistance characterization of locally anisotropic transparent conductive
      films made of aligned metal-enriched single-walled carbon nanotubes.
AB  - One-dimensional conductive fillers such as single-walled carbon nanotubes (SWNTs)
      can be aggregated and aligned during transparent conductive film (TCF) formation
      by the vacuum filtration method. The potential error of analysing the average
      sheet resistance of these anisotropic films, using the four-point probe in-line
      method and the conversion formula developed assuming uniform isotropic material
      properties, was systematically investigated by finite element analysis and
      experiments. The finite element analysis of anisotropic stripe-patterned TCFs
      with alternating low (rho1) and high (rho2) resistivities revealed that the
      estimated average sheet resistance approached rho1/t when the probes were
      parallel to the aligned nanotubes. The thickness of the film is t. It was more
      close to rho2/t when the probes were perpendicular to the aligned tubes. Indeed,
      TCFs fabricated by the vacuum filtration method using metal-enriched SWNTs
      exhibited highly anisotropic local regions where tubes were aggregated and
      aligned. The local sheet resistances of randomly oriented, aligned, and
      perpendicular tube regions of the TCF at a transmittance of 89.9% were 5000, 2.4,
      and 12 300 Omega ?(-1), respectively. Resistivities of the aggregated and aligned
      tube region (rho1 = 1.2 * 10(-5) Omega cm) and the region between tubes (rho2 =
      6.2 * 10(-2) Omega cm) could be approximated with the aid of finite element
      analysis. This work demonstrates the potential error of characterizing the
      average sheet resistance of anisotropic TCFs using the four-point probe in-line
      method since surprisingly high or low values could be obtained depending on the
      measurement angle. On the other hand, a better control of aggregation and
      alignment of nanotubes would realize TCFs with a very small anisotropic
      resistivity and a high transparency. 

PMID- 25075463
TI  - Acute transient myopia with shallowing of the anterior chamber induced by
      sulfamethoxazole in a patient with pseudoxanthoma elasticum.
AB  - PURPOSE: To report a case of acute transient myopia with anterior chamber
      shallowing induced by sulfamethoxazole in a patient with pseudoxanthoma elasticum
      (PXE). DESIGN: Observational case report. METHODS: A case report of a 45-year-old
      woman who presented with bilateral acute myopia, anterior chamber shallowing, and
      intraocular hypertension induced by sulfamethoxazole and was found to have PXE.
      Initial and follow-up examination findings were reviewed. RESULTS: On first
      examination, bilateral myopic shift of 4.25 D, bilateral narrowed angles, and
      ocular hypertension (36 mm Hg right eye and 38 mm Hg left eye) were found.
      Pentacam images documented the anterior displacement of the iris-lens diaphragm.
      Undilated fundus examination disclosed bilateral angioid streaks radiating from
      the papilla. Several redundant skin folds on the neck and axillae were found on
      external examination. With sulfamethoxazole discontinuation and administration of
      topical intraocular pressure-lowering drops, there was complete clinical
      resolution within 1 week. The diagnosis of PXE was confirmed by biopsy of the
      skin lesions. CONCLUSIONS: Acute myopia with angle narrowing is an extremely rare
      sulfamethoxazole side effect, and its relationship, if any, with PXE is unknown.
      As far as we know, this is the first reported case of PXE presenting with
      bilateral angle narrowing induced by sulfamethoxazole.

PMID- 25075462
TI  - Comparison of the clinical disc margin seen in stereo disc photographs with
      neural canal opening seen in optical coherence tomography images.
AB  - PURPOSE: To compare neural canal opening (NCO) with the clinical optic disc
      margin (DM) seen and to investigate the planarity of the NCO in normal human
      optic nerve heads (ONH). METHODS: Sixteen eyes were imaged. Twelve healthy eyes
      were selected for planarity and 9 for NCO and DM correspondence. All subjects
      were subjected to a visual field examination, stereo disc photograph (SDP),
      scanning laser ophthalmoscopy, clinical examination with a fellowship trained
      glaucoma specialist, and optical coherence tomography imaging. Three reviewers
      delineated the NCO and inner limiting membrane on optical coherence tomography
      images. The clinical DM was delineated by a glaucoma specialist while viewing
      SDPs. Plane error was calculated for NCO and for Bruch membrane (BM) at distances
      80 and 120 MUm from NCO. RESULTS: The NCO segmentation interrater variability was
      low with an average coefficient of variation of 2.7%. A regional variation of the
      SDP and NCO correspondence was observed, wherein the temporal region had the
      largest coefficient of variation. The plane error of the NCO and BM were similar
      and was approximately 12 MUm, which is small relative to an average DM diameter
      of 1.7 mm. CONCLUSIONS: The BM opening has a good correspondence with the
      clinical DM seen in SDPs. NCO delineation seemed to be reliable. The BM and NCO
      are relatively planar in normal humans and can be further evaluated for
      longitudinal studies to observe stability.

PMID- 25075465
TI  - Fullerene derivatives with increased dielectric constants.
AB  - The invention of new organic materials with high dielectric constants is of
      extreme importance for the development of organic-based devices such as organic
      solar cells. We report on a synthetic way to increase the dielectric constant of
      fullerene derivatives. It is demonstrated that introducing triethylene glycol
      monoethyl ether (teg) side chains into fulleropyrrolidines increases the
      dielectric constant by ~46 percent without devaluation of optical properties,
      electron mobility and the energy level of the compound.

PMID- 25075466
TI  - Local distribution and abundance of Cardisoma guanhumi Latreille, 1928
      (Brachyura: Gecarcinidae) in southern Brazil.
AB  - The blue land crab, Cardisoma guanhumi Latreille, 1828 (Brachyura: Gecarcinidae)
      is officially included in the list of over-exploited species in Brazil, although
      still abundantly found in the state of Santa Catarina, the southern limit of its
      distribution. This species was found in forested areas, gardens, and grassy
      areas, including crabs with carapace width larger than 80mm. The existence of
      this population with these characteristics is surprising, since there is only one
      official record of the species in the southern region. The objectives of this
      study are to estimate the abundance and occupation patterns of C. guanhumi in
      this region. Correlations with conservation were discussed. The absolute
      abundance of crabs in the middle of summer activity was established for an area
      of 100,000 m2. A smaller area was mapped and divided into sampling units for
      statistical analyses. We distributed approximately 240 crabs in a forested area
      of about 3,000 m2 and 150 crabs in grassy areas (90,000 m2). The statistical test
      of Kruskal-Wallis test showed that there are significant differences between the
      sizes of the openings of the galleries inside the forest and that located in
      grassy areas. In the forest, the openings tend to be much larger. Burrows were
      found at a distance of 150 metres from the channel. The number of galleries was
      higher in the forested area, although the burrows were more densely grouped in
      grassy areas. Although C. guanhumi seems to be adjusting well to changes caused
      by human occupation, small forested areas are more conducive to growth and
      conservation of this species. 

PMID- 25075467
TI  - Asymmetric one-pot synthesis of 1,3-oxazolidines and 1,3-oxazinanes via
      hemiaminal intermediates.
AB  - A highly efficient method for the enantioselective one-pot synthesis of 1,3
      oxazolidines and 1,3-oxazinanes has been reported. The reaction proceeds via the
      formation of hemiaminal intermediates obtained by the enantioselective addition
      of respective alcohols to imines catalyzed by a chiral magnesium phosphate
      catalyst, followed by intramolecular cyclization under mildly basic conditions. A
      wide range of substrates have been converted to the respective chiral
      heterocyclic products in high yields and with excellent enantioselectivities
      using this one-pot procedure. 

PMID- 25075468
TI  - Whole-genome analyses reveals the animal origin of a rotavirus G4P[6] detected in
      a child with severe diarrhea.
AB  - Group A rotaviruses are a major cause of severe gastroenteritis in children
      worldwide. Currently, two rotavirus vaccines are being used in vaccination
      programs, and one of the factors involved in lower vaccine efficacy is the
      mismatch among the circulating strains and the vaccine strains. Thus, the
      emergence of animal strains in the human population could affect the efficacy of
      vaccination programs. Here we report the presence of a G4P[6] strain in a
      Paraguayan child presenting acute gastroenteritis in 2009. Genomic analyses
      revealed that the strain presents a porcine-like genome (G4-P[6]-I1-R1-C1-M1-A8
      N1-T7-E1-H1), suggesting a direct animal-to-human transmission. Continuous
      surveillance of rotaviruses in humans and animals will help us to better
      understand rotavirus epidemiology and evolution. 

PMID- 25075469
TI  - Nuclear expression of STAT6 in dedifferentiated liposarcomas with a solitary
      fibrous tumor-like morphology: a diagnostic pitfall.

PMID- 25075470
TI  - A home-brew real-time PCR assay for reliable detection and quantification of
      mature miR-122.
AB  - miR-122 is a liver-specific miRNA that has significant gene expression
      alterations in response to specific pathophysiological circumstances of liver
      such as drug-induced liver injury, hepatocellular carcinoma, and hepatitis B and
      C virus infections. Therefore, accurate and precise quantification of miR-122 is
      very important for clinical diagnostics. However, because of the lack of in vitro
      diagnostics assays for miR-122 detection and quantification of the existence of
      an open-source assay could inevitably provide external evaluation by other
      researchers and the chance of promoting the assay when required. The aim of this
      study was to develop a Taqman real-time polymerase chain reaction assay, which is
      capable of robust and reliable quantification of miR-122 in different sample
      types. We used stem loop methodology to design a specific Taqman real-time
      polymerase chain reaction assay for miR-122. This technique enabled us to
      reliably and reproducibly quantify short-length oligonucleotides such as miR-122.
      The specificity, sensitivity, interassay and intra-assay, and the dynamic range
      of the assay were experimentally determined by their respective methodology. The
      assay had a linear dynamic range of 3E to 4.8E miR-122 copies/reaction and the
      limit of detection was determined to be between 960 and 192 copies/reaction with
      95% confidence interval. The assay gave a coefficient of variation for the Ct
      values of <1.4% and 0.78% for intra-assay and interassay, respectively. Taking
      into account that miR-122 is expressed in >50,000 copies per hepatocyte, this
      assay is able to suffice the need for reliable detection and quantification of
      this miRNA. Therefore, this study can be considered as a start point for
      standardizing miR-122 quantification. 

PMID- 25075471
TI  - Exogenous pigmentation mimicking acral melanoma: a case of Talon d'Oyer.

PMID- 25075472
TI  - Editorial--Analytical sciences in Brazil.

PMID- 25075473
TI  - Factors associated with general surgery residents' desire to leave residency
      programs: a multi-institutional study.
AB  - IMPORTANCE: General surgical residency continues to experience attrition. To
      date, work hour amendments have not changed the annual rate of attrition.
      OBJECTIVE: To determine how often categorical general surgery residents seriously
      consider leaving residency. DESIGN, SETTING, AND PARTICIPANTS: At 13 residency
      programs, an anonymous survey of 371 categorical general surgery residents and 10
      year attrition rates for each program. Responses from those who seriously
      considered leaving surgical residency were compared with those who did not. MAIN
      OUTCOMES AND MEASURES: Factors associated with the desire to leave residency.
      RESULTS: The survey response rate was 77.6%. Overall, 58.0% seriously considered
      leaving training. The most frequent reasons for wanting to leave were sleep
      deprivation on a specific rotation (50.0%), an undesirable future lifestyle
      (47.0%), and excessive work hours on a specific rotation (41.4%). Factors most
      often cited that kept residents from leaving were support from family or
      significant others (65.0%), support from other residents (63.5%), and perception
      of being better rested (58.9%). On univariate analysis, older age, female sex,
      postgraduate year, training in a university program, the presence of a faculty
      mentor, and lack of Alpha Omega Alpha status were associated with serious
      thoughts of leaving surgical residency. On multivariate analysis, only female sex
      was significantly associated with serious thoughts of leaving residency (odds
      ratio, 1.2; 95% CI, 1.1-1.3; P = .003). Eighty-six respondents were from
      historically high-attrition programs, and 202 respondents were from historically
      low-attrition programs (27.8% vs 8.4% 10-year attrition rate, P = .04). Residents
      from high-attrition programs were more likely to seriously consider leaving
      residency (odds ratio, 1.8; 95% CI, 1.0-3.0; P = .03). CONCLUSIONS AND RELEVANCE:
      A majority of categorical general surgery residents seriously consider leaving
      residency. Female residents are more likely to consider leaving. Thoughts of
      leaving seem to be associated with work conditions on specific rotations rather
      than with overall work hours and are more prevalent among programs with
      historically high attrition rates.

PMID- 25075474
TI  - Mannose-binding lectin and susceptibility to human retrovirus infections.

PMID- 25075475
TI  - Sexual transmission of human T-cell lymphotropic virus type 1.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in many parts of the
      world and is primarily transmitted through sexual intercourse or from mother to
      child. Sexual transmission occurs more efficiently from men to women than women
      to men and might be enhanced by sexually transmitted diseases that cause ulcers
      and result in mucosal ruptures, such as syphilis, herpes simplex type 2 (HSV-2),
      and chancroid. Other sexually transmitted diseases might result in the
      recruitment of inflammatory cells and could increase the risk of HTLV-1
      acquisition and transmission. Additionally, factors that are associated with
      higher transmission risks include the presence of antibodies against the viral
      oncoprotein Tax (anti-Tax), a higher proviral load in peripheral blood
      lymphocytes, and increased cervicovaginal or seminal secretions. Seminal fluid
      has been reported to increase HTLV replication and transmission, whereas male
      circumcision and neutralizing antibodies might have a protective effect.
      Recently, free virions were discovered in plasma, which reveals a possible new
      mode of HTLV replication. It is unclear how this discovery might affect the
      routes of HTLV transmission, particularly sexual transmission, because HTLV
      transmission rates are significantly higher from men to women than women to men. 

PMID- 25075476
TI  - Molecular characterization of Torque teno virus and SEN virus co-infection with
      HIV in patients from Southern Iran.
AB  - INTRODUCTION: Torque teno virus (TTV) and SEN virus are circular single-stranded
      DNA viruses that cause blood-borne infections. The SEN virus (SEN-V) was
      originally detected in the serum of an injection drug user infected with human
      immunodeficiency virus (HIV). Recently TTV was discovered as a potential
      causative agent of non-A-E hepatitis. The aim of this study was to investigate
      the prevalence of the SEN-V-D/H and TTV in HIV patients and healthy blood donors
      in Iran. METHODS: One hundred and fifty HIV patients with a mean age of 50.46 +/-
      18.46 years and 150 healthy blood donors with a mean age of 48.16 +/- 13.73 years
      were included in this study. TTV and SEN-V were detected by the PCR and were
      quantitatively assayed by competitive PCR (nested and semi-nested PCR).
      Restriction fragment length polymorphisms (RFLPs) were used to determine the
      heterogeneity of TTV. RESULTS: TTV and SEN-V were detected 96 (64%) and 84 (56%)
      of 150 HIV patients respectively. These rates were 34% (n=51) and 37.33% (n=56)
      in healthy blood donors (significant, p<0.05). PCR detected SEN-V/TTV DNA from 32
      of the healthy blood donors (21.33%), while 65 (43.33%) of HIV patients were
      positive for SEN-V/TTV DNA. Of 150 HIV patients, 32.66% and 23.33% were positive
      for SEN-V-H and SEN-V-D, respectively and 18.66% (n=28) were co-infected with SEN
      V-D/H. CONCLUSIONS: The prevalence of SEN-VD/H and TTV is higher in HIV patients
      than in healthy blood donors in Southern Iran. Our results suggest that TTV and
      SEN-V might play a role in the development of liver disease in patients with
      immunodeficiency diseases.

PMID- 25075477
TI  - Serological evidence for Saint Louis encephalitis virus in free-ranging New World
      monkeys and horses within the upper Parana River basin region, Southern Brazil.
AB  - INTRODUCTION: Saint Louis encephalitis virus (SLEV) primarily occurs in the
      Americas and produces disease predominantly in humans. This study investigated
      the serological presence of SLEV in nonhuman primates and horses from southern
      Brazil. METHODS: From June 2004 to December 2005, sera from 133 monkeys (Alouatta
      caraya, n=43; Sapajus nigritus, n=64; Sapajus cay, n=26) trap-captured at the
      Parana River basin region and 23 blood samples from farm horses were obtained and
      used for the serological detection of a panel of 19 arboviruses. All samples were
      analyzed in a hemagglutination inhibition (HI) assay; positive monkey samples
      were confirmed in a mouse neutralization test (MNT). Additionally, all blood
      samples were inoculated into C6/36 cell culture for viral isolation. RESULTS:
      Positive seroreactivity was only observed for SLEV. A prevalence of SLEV
      antibodies in sera was detected in Alouatta caraya (11.6%; 5/43), Sapajus
      nigritus (12.5%; 8/64), and S. cay (30.8%; 8/26) monkeys with the HI assay. Of
      the monkeys, 2.3% (1/42) of A. caraya, 6.3% 94/64) of S. nigritus, and 15.4%
      (4/26) of S. cay were positive for SLEV in the MNT. Additionally, SLEV antibodies
      were detected by HI in 39.1% (9/23) of the horses evaluated in this study.
      Arboviruses were not isolated from any blood sample. CONCLUSIONS: These results
      confirmed the presence of SLEV in nonhuman primates and horses from southern
      Brazil. These findings most likely represent the first detection of this virus in
      nonhuman primates beyond the Amazon region. The detection of SLEV in animals
      within a geographical region distant from the Amazon basin suggests that there
      may be widespread and undiagnosed dissemination of this disease in Brazil.

PMID- 25075478
TI  - A complete molecular biology assay for hepatitis C virus detection,
      quantification and genotyping.
AB  - INTRODUCTION: Molecular biology procedures to detect, genotype and quantify
      hepatitis C virus (HCV) RNA in clinical samples have been extensively described.
      Routine commercial methods for each specific purpose (detection, quantification
      and genotyping) are also available, all of which are typically based on
      polymerase chain reaction (PCR) targeting the HCV 5' untranslated region (5'UTR).
      This study was performed to develop and validate a complete serial laboratory
      assay that combines real-time nested reverse transcription-polymerase chain
      reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) techniques
      for the complete molecular analysis of HCV (detection, genotyping and viral load)
      in clinical samples. METHODS: Published HCV sequences were compared to select
      specific primers, probe and restriction enzyme sites. An original real-time
      nested RT-PCR-RFLP assay was then developed and validated to detect, genotype and
      quantify HCV in plasma samples. RESULTS: The real-time nested RT-PCR data were
      linear and reproducible for HCV analysis in clinical samples. High correlations
      (> 0.97) were observed between samples with different viral loads and the
      corresponding read cycle (Ct - Cycle threshold), and this part of the assay had a
      wide dynamic range of analysis. Additionally, HCV genotypes 1, 2 and 3 were
      successfully distinguished using the RFLP method. CONCLUSIONS: A complete serial
      molecular assay was developed and validated for HCV detection, quantification and
      genotyping.

PMID- 25075479
TI  - Risk factors for hepatitis C virus transmission in the municipality of Catanduva,
      State of Sao Paulo: a case-control study.
AB  - INTRODUCTION: Hepatitis C virus (HCV) is primarily transmitted via contact with
      the blood of infected patients, although the form of contact has not been
      identified for a significant percentage of carriers. The present study evaluated
      possible risk factors for HCV transmission in a medium-sized town located in the
      northwest region of the State of Sao Paulo. METHODS: This was a case-control
      study, with the case group consisting of 190 chronic HCV carriers older than 18
      years residing in the municipality of Catanduva. The control group also consisted
      of 190 individuals with HCV-negative serology. The groups were paired (1:1) for
      gender, age range (+/- five years), and place of residence. The same structured
      questionnaire was applied to all subjects, who gave written informed consent to
      participate in the study. The data were statistically analyzed using crude and
      adjusted logistic regression, and the results were expressed as odds ratios with
      a 95% confidence interval. RESULTS: The demographic profiles of the groups
      indicated a predominance of males (68.9%) and mean ages of 47.1 years (case
      group) and 47.3 years (control group). After adjusting for conditional
      regression, the following factors were found to represent risks for HCV: history
      of sexually transmitted disease (STD) and blood transfusion; accidents with
      syringes and/or needles; tattoos; and the use of non-injectable drugs and
      injectable medications. CONCLUSIONS: The transmission of HCV via the blood route
      has been well characterized. Other forms of contact with human blood and/or
      secretions are likely to transmit the virus, although with a lower frequency of
      occurrence.

PMID- 25075480
TI  - Lack of evidence for human infection with Xenotropic murine leukemia virus
      related virus in the Brazilian Amazon basin.
AB  - INTRODUCTION: This study confirmed the absence of natural infection with
      Xenotropic murine leukemia virus-related virus (XMRV) or XMRV-related disease in
      human populations of the Brazilian Amazon basin. We demonstrated that 803
      individuals of both sexes, who were residents of Belem in the Brazilian State of
      Para, were not infected with XMRV. METHODS: Individuals were divided into 4
      subgroups: healthy individuals, individuals infected with human immunodeficiency
      virus, type 1 (HIV-1), individuals infected with human T-lymphotrophic virus,
      types 1 or 2 (HTLV-1/2), and individuals with prostate cancer. XMRV infection was
      investigated by nested PCR to detect the viral gag gene and by quantitative PCR
      to detect pol. RESULTS: There was no amplification of either gag or pol segments
      from XRMV in any of the samples examined. CONCLUSIONS: This study supports the
      conclusions of the studies that eventually led to the retraction of the original
      study reporting the association between XMRV and human diseases.

PMID- 25075481
TI  - Biology of Triatoma carcavalloi Jurberg, Rocha & Lent, 1998 under laboratory
      conditions.
AB  - INTRODUCTION: Triatoma carcavalloi is a wild species that is found in sympatry
      with Triatoma rubrovaria and Triatoma circummaculata, which are vectors of
      Trypanosoma cruzi currently found in rural areas of Rio Grande do Sul, Brazil.
      METHODS: Fertility was assessed and to determine the incubation period, the eggs
      were observed until hatching. The first meal was offered to 1st stage nymphs. The
      intermolt period was also determined. The number of blood meals was quantified at
      each nymphal stage and the resistance to fasting as the period between ecdysis
      and death. Mortality was assessed and longevity was determined by recording the
      time that elapsed from molting to the adult stage and until death. The
      developmental cycle was assessed by recording the length in days of each stage
      from molting to adult hood. RESULTS: The average incubation period was 22.7 days.
      The average first meal occurred 3.1 days after hatching. The 5th stage nymph to
      adult intermolting period was the longest at 193.4 days. The average number of
      feedings during nymphal development was 13.4. The resistance to fasting assay
      indicated that the 3rd, 4th and 5th stage nymphs presented higher resistance than
      did adults. The highest mortality rate was observed in the 3rd stage nymphs
      (22.2%). The average length of adult survival was 25.6 weeks, and the average
      total life cycle lasted 503.4 days. CONCLUSIONS: This study is the first report
      on the biology of T. carcavalloi that fed on mice. The presented findings expand
      the bionomic knowledge of these species.

PMID- 25075482
TI  - Composition, abundance and aspects of temporal variation in the distribution of
      Anopheles species in an area of Eastern Amazonia.
AB  - INTRODUCTION: The diverse and complex environmental conditions of the Amazon
      Basin favor the breeding and development of Anopheles species. This study aimed
      to describe the composition, abundance and temporal frequency of Anopheles
      species and to correlate these factors with precipitation, temperature and
      relative humidity. METHODS: The study was conducted in the District of Coracao,
      State of Amapa, Brazil. Samples were collected monthly during three consecutive
      nights, from 6:00 PM to 10:00 PM, from December 2010 to November 2011. In
      addition, four 12-hour collections (i.e., 6:00 PM to 6:00 AM) were performed
      during this period. RESULTS: A total of 1,230 Anopheles specimens were collected.
      In the monthly collections, Anopheles darlingi was the predominant species,
      followed by An. braziliensis and An. albitarsis s.l., whereas An. darlingi, An.
      peryassui and An. braziliensis were the most frequent species collected in the 12
      hour collections. The greatest number of anophelines was collected in September
      (the dry season). The highest frequency of anophelines was observed for An.
      darlingi during September, when there were the least rainfalls of the year, along
      with lower relative humidity and higher temperatures. There was little variation
      in the abundance of this species in other months, with the exception of slight
      increases in February, July and August. CONCLUSIONS: The major malaria vectors,
      An. darlingi and An. albitarsis s.l. (likely An. marajoara), were the most
      abundant species collected in the study area. Consequently, prevention and
      control measures should be taken to prevent malaria outbreaks in the District of
      Coracao.

PMID- 25075483
TI  - Nosocomial infections in a neonatal intensive care unit during 16 years: 1997
      2012.
AB  - INTRODUCTION: Surveillance of nosocomial infections (NIs) is an essential part of
      quality patient care; however, there are few reports of National Healthcare
      Safety Network (NHSN) surveillance in neonatal intensive care units (NICUs) and
      none in developing countries. The purpose of this study was to report the
      incidence of NIs, causative organisms, and antimicrobial susceptibility patterns
      in a large cohort of neonates admitted to the NICU during a 16-year period.
      METHODS: The patients were followed 5 times per week from birth to discharge or
      death, and epidemiological surveillance was conducted according to the NHSN.
      RESULTS: From January 1997 to December 2012, 4,615 neonates, representing 62,412
      patient-days, were admitted to the NICU. The device-associated infection rates
      were as follows: 17.3 primary bloodstream infections per 1,000 central line-days
      and 3.2 pneumonia infections per 1,000 ventilator-days. A total of 1,182
      microorganisms were isolated from sterile body site cultures in 902 neonates.
      Coagulase-negative staphylococci (CoNS) (34.3%) and Staphylococcus aureus (15.6%)
      were the most common etiologic agents isolated from cultures. The incidences of
      oxacillin-resistant CoNS and Staphylococcus aureus were 86.4% and 28.3%,
      respectively. CONCLUSIONS: The most important NI remains bloodstream infection
      with staphylococci as the predominant pathogens, observed at much higher rates
      than those reported in the literature. Multiresistant microorganisms, especially
      oxacillin-resistant staphylococci and gram-negative bacilli resistant to
      cephalosporin were frequently found. Furthermore, by promoting strict hygiene
      measures and meticulous care of the infected infants, the process itself of
      evaluating the causative organisms was valuable.

PMID- 25075484
TI  - Occurrence of potentially pathogenic Vibrio in oysters (Crassostrea gigas) and
      waters from bivalve mollusk cultivations in the South Bay of Santa Catarina.
AB  - INTRODUCTION: This research aimed to identify and quantify potentially pathogenic
      Vibrio from different cultivations of bivalve shellfish in the State of Santa
      Catarina, Brazil, and water regions in the South Bay, as well as correlate the
      incidence of these microorganisms with the physicochemical parameters of marine
      waters. METHODS: Between October 2008 and March 2009, 60 oyster and seawater
      samples were collected from six regions of bivalve mollusk cultivation, and these
      samples were submitted for Vibrio counts. RESULTS: Twenty-nine (48.3%) oyster
      samples were revealed to be contaminated with one or more Vibrio species. The
      Vibrio parahaemolyticus and Vibrio vulnificus counts in the samples ranged from <
      0.5 log10 Most Probable Number (MPN) g(-1) to 2.3 log10 MPN g(-1) oyster and from
      < 0.5 log10 MPN g(-1) to 2.1 log10 MPN g(-1) oyster, respectively. Of the 60
      seawater samples analyzed, 44 (73.3%) showed signs of contamination with one or
      more vibrio species. The counts of V. parahaemolyticus and V. vulnificus in the
      samples ranged from < 0.3 log10 MPN.100mL(-1) to 1.7 log10MPN.100mL(-1) seawater
      and from < 0.3 log10 MPN.100mL(-1) to 2.0 log10 MPN.100mL(-1) seawater,
      respectively. A positive correlation between V. vulnificus counts and the
      seawater temperature as well as a negative correlation between the V.
      parahaemolyticus counts and salinity were observed. CONCLUSIONS: The results
      suggest the need to implement strategies to prevent vibrio diseases from being
      transmitted by the consumption of contaminated bivalve shellfish.

PMID- 25075485
TI  - Evaluation of preventative and control measures for congenital syphilis in State
      of Mato Grosso.
AB  - INTRODUCTION: Congenital syphilis is an important health problem in Brazil. This
      study assessed measures aimed at the prevention and control of syphilis in the
      State of Mato Grosso and its capital, Cuiaba. METHODS: A descriptive study cross
      sectional and of time trends assessing the congenital syphilis was performed in
      Cuiaba and Mato Grosso between 2001 and 2011. We compared maternal
      sociodemographic characteristics and health care utilization related to cases of
      congenital syphilis during the periods from 2001 to 2006 and from 2007 to 2011.
      We assessed the temporal trends in this disease's incidence using a simple linear
      regression. RESULTS: Between 2001 and 2006 in Mato Grosso, 86.8% of the mothers
      who had live births with congenital syphilis received prenatal care, 90.6%
      presented with a nontreponemal test reagent at delivery, 96.2% had no information
      regarding a treponemal confirmatory test at delivery, and 77.6% received
      inadequate treatment for syphilis; additionally, 75.8% of their partners were not
      treated. There was a statistically significant reduction in prenatal visits (p =
      0.004) and an increase in the proportion of mothers reactive to nontreponemal
      tests at delivery (p = 0.031) between the two periods. No other variables were
      found to differ significantly between the periods. In Cuiaba, we observed a
      similar distribution of variables. In the state and in the capital, the
      increasing trend of congenital syphilis was not statistically significant.
      CONCLUSIONS: The high incidence of congenital syphilis in Mato Grosso and the low
      levels of health care indicators for pregnant women with syphilis suggest the
      need to improve the coverage and quality of prenatal care.

PMID- 25075486
TI  - Platelet profile is associated with clinical complications in patients with vivax
      and falciparum malaria in Colombia.
AB  - INTRODUCTION: Thrombocytopenia is a common complication in malaria patients. The
      relationship between abnormal platelet profile and clinical status in malaria
      patients is unclear. In low and unstable endemic regions where vivax malaria
      predominates, the hematologic profiles of malaria patients and their clinical
      utility are poorly understood. The aim of this study was to characterize the
      thrombograms of malaria patients from Colombia, where Plasmodium vivax infection
      is common, and to explore the relationship between thrombograms and clinical
      status. METHODS: Eight hundred sixty-two malaria patients were enrolled,
      including 533 (61.8%) patients infected with Plasmodium falciparum, 311 (36.1%)
      patients infected with Plasmodium vivax and 18 (2.1%) patients with mixed
      infections. RESULTS: The most frequently observed changes were low platelet count
      (PC) and high platelet distribution width (PDW), which were observed in 65% of
      patients; thrombocytopenia with <50,000 platelets/uL was identified in 11% of
      patients. Patients with complications had lower PC and plateletcrit (PT) and
      higher PDW values. A higher risk of thrombocytopenia was identified in patients
      with severe anemia, neurologic complications, pulmonary complications, liver
      dysfunction, renal impairment and severe hypoglycemia. The presence of
      thrombocytopenia (<150,000 platelets/uL) was associated with a higher probability
      of liver dysfunction. CONCLUSIONS: Young age, longer duration of illness and
      higher parasitemia are associated with severe thrombocytopenia. Our study showed
      that thrombocytopenia is related to malaria complications, especially liver
      dysfunction. High PDW in patients with severe malaria may explain the mechanisms
      of thrombocytopenia that is common in this group of patients.

PMID- 25075487
TI  - Temporal, spatial and spatiotemporal analysis of the occurrence of visceral
      leishmaniasis in humans in the City of Birigui, State of Sao Paulo, from 1999 to
      2012.
AB  - INTRODUCTION: In 1999, Birigui and Aracatuba were the first municipalities in the
      State of Sao Paulo to present autochthonous cases of visceral leishmaniasis in
      humans (VLH). The aim of this study was to describe the temporal, spatial and
      spatiotemporal behaviors of VLH in Birigui. METHODS: Secondary data were obtained
      from the Notifiable Diseases Information System from 1999 to 2012. The incidence,
      mortality and case fatality rates by sex and age were calculated. The cases of
      VLH were geocoded and grouped according to census tracts. Local empirical
      Bayesian incidence rates were calculated. The existence of spatial and
      spatiotemporal clusters was investigated using SaTScan software. RESULTS: There
      were 156 confirmed cases of autochthonous VLH. The incidence rate was higher in
      the 0-4-year-old children, and the mortality and case fatality rates were higher
      in people aged 60 years and older. The peaks of incidence occurred in 2006 and
      2011. The Bayesian rates identified the presence of VLH in all of the census
      tracts in the municipality; however, spatial and spatiotemporal clusters were
      found in the central area of the municipality. CONCLUSIONS: Birigui, located in
      the Aracatuba region, has recently experienced increasing numbers of VLH cases;
      this increase is contrary to the behavior observed over the entire region, which
      has shown a decreasing trend in the number of VLH cases. The observations that
      the highest incidence is in children 0-4 years old and the highest mortality is
      in people 60 years and older are in agreement with the expected patterns of VLH.

PMID- 25075488
TI  - Evaluation of diagnostic tests for Wuchereria bancrofti infection in Brazilian
      schoolchildren.
AB  - INTRODUCTION: Since the launch of the Global Programme to Eliminate Lymphatic
      Filariasis, more than 70% of the endemic countries have implemented mass drug
      administration (MDA) to interrupt disease transmission. The monitoring of
      filarial infection in sentinel populations, particularly schoolchildren, is
      recommended to assess the impact of MDA. A key issue is choosing the appropriate
      tools for these initial assessments (to define the best intervention) and for
      monitoring transmission. METHODS: This study compared the pre-MDA performance of
      five diagnostic methods, namely, thick film test, Knott's technique, filtration,
      Og4C3-ELISA, and the AD12-ICT card test, in schoolchildren from Brazil. Venous
      and capillary blood samples were collected between 11 pm and 1 am. The
      microfilarial loads were analyzed with a negative binomial regression, and the
      prevalence and associated 95% confidence intervals were estimated for all
      methods. The accuracies of the AD12-ICT card and Og4C3-ELISA tests were assessed
      against the combination of parasitological test results. RESULTS: A total of 805
      schoolchildren were examined. The overall and stratified prevalence by age group
      and gender detected by Og4C3-ELISA and AD12-ICT were markedly higher than the
      prevalence estimated by the parasitological methods. The sensitivity of the AD12
      ICT card and Og4C3-ELISA tests was approximately 100%, and the positive
      likelihood ratios were above 6. The specificity of the Og4C3-ELISA was higher
      than that of the AD12-ICT at different prevalence levels. CONCLUSIONS: The ICT
      card test should be the recommended tool for monitoring school-age populations
      living in areas with ongoing or completed MDA.

PMID- 25075489
TI  - Hematologic profile of hematophagous Desmodus rotundus bats before and after
      experimental infection with rabies virus.
AB  - INTRODUCTION: Hematophagous Desmodus rotundus bats play an important role in the
      rabies lifecycle. This study describes the hematological profile of these bats
      before and after experimental infection with rabies virus. METHODS: Cells counts
      were performed in a Neubauer chamber. RESULTS: The average values of erythrocytes
      and leucocytes counts in blood before experimental infections were 9.97 *
      10(6)mm3 and 4.80 * 10(3)mm3, respectively. Neutrophils represented 69.9% of
      white blood cells and the lymphocytes represented 26.9%. Following the
      experimental infections, the average numbers of erythrocytes and leucocytes was
      9.43 * 106mm3 and 3.98 * 10(3)mm3, respectively. Neutrophils represented 40% of
      white blood cells and the lymphocytes represented 59%. CONCLUSIONS: The
      hematological profile given in this study can serve as reference values for D.
      rotundus bats.

PMID- 25075491
TI  - Temperature and atmospheric pressure may be considered as predictors for the
      occurrence of bacillary dysentery in Guangzhou, Southern China.
AB  - INTRODUCTION: The control of bacillary dysentery (BD) remains a big challenge for
      China. METHODS: Negative binomial multivariable regression was used to study
      relationships between meteorological variables and the occurrence of BD during
      the period of 2006-2012. RESULTS: Each 1 degrees C rise of temperature
      corresponded to an increase of 3.60% (95%CI, 3.03% to 4.18%) in the monthly
      number of BD cases, whereas a 1 hPa rise in atmospheric pressure corresponded to
      a decrease in the number of BD cases by 2.85% (95%CI = 3.34% to 2.37% decrease).
      CONCLUSIONS: Temperature and atmospheric pressure may be considered as predictors
      for the occurrence of BD in Guangzhou.

PMID- 25075490
TI  - Performance of the Vitek 2 system software version 5.03 in the bacterial
      identification and antimicrobial susceptibility test: evaluation study of
      clinical and reference strains of Gram-positive cocci.
AB  - INTRODUCTION: The genera Enterococcus, Staphylococcus and Streptococcus are
      recognized as important Gram-positive human pathogens. The aim of this study was
      to evaluate the performance of Vitek 2 in identifying Gram-positive cocci and
      their antimicrobial susceptibilities. METHODS: One hundred four isolates were
      analyzed to determine the accuracy of the automated system for identifying the
      bacteria and their susceptibility to oxacillin and vancomycin. RESULTS: The
      system correctly identified 77.9% and 97.1% of the isolates at the species and
      genus levels, respectively. Additionally, 81.8% of the Vitek 2 results agreed
      with the known antimicrobial susceptibility profiles. CONCLUSION: Vitek 2
      correctly identified the commonly isolated strains; however, the limitations of
      the method may lead to ambiguous findings.

PMID- 25075492
TI  - The first canine visceral leishmaniasis outbreak in Campinas, State of Sao Paulo
      Southeastern Brazil.
AB  - INTRODUCTION: Early detection of American visceral leishmaniasis (AVL) outbreak
      in animals is crucial for controlling this disease in non-endemic areas. METHODS:
      Epidemiological surveillance (2009-2012) was performed in Campinas, State of Sao
      Paulo, Brazil. RESULTS: In 2009, Leishmania chagasi was positively identified in
      four dogs. Entomological research and three serological studies (2010-2012) were
      undertaken as monitoring measures; these approaches revealed a moderate
      prevalence of Leishmania present in 4% of the canine population. Nyssomyia
      whitmani and Lutzomyia longipalpis were the predominant species identified.
      CONCLUSIONS: Detection of an AVL outbreak in dogs in an area with an evolving
      natural landscape containing sand flies is crucial for control programs.

PMID- 25075493
TI  - Effects of Rosmarinus officinalis essential oil on germ tube formation by Candida
      albicans isolated from denture wearers.
AB  - INTRODUCTION: The aim of this study was to investigate the effects of Rosmarinus
      officinalis essential oil on germ tube formation by Candida albicans isolated
      from denture wearers. METHODS: Ten C. albicans isolates recovered from denture
      wearers were tested using 10% fetal bovine serum with or without 4% R.
      officinalis essential oil. RESULTS: The essential oil from R. officinalis
      completely inhibited germ tube formation in the investigated C. albicans
      isolates. CONCLUSIONS: The results demonstrate that the essential oil of R.
      officinalis modulates C. albicans pathogenicity through its primary virulence
      factor (i.e., germ tube formation was suppressed).

PMID- 25075494
TI  - The epidemiological scenario of feline sporotrichosis in Rio de Janeiro, State of
      Rio de Janeiro, Brazil.
AB  - INTRODUCTION: Sporotrichosis is a mycosis affecting both humans and animals.
      Within the context of the ongoing sporotrichosis epidemic in the State of Rio de
      Janeiro, Brazil, sick cats plays an important role in the zoonotic transmission.
      The aim of this study was to update the number of feline cases diagnosed at the
      Fundacao Oswaldo Cruz (2005-2011). METHODS: The medical records of the cats
      followed were reviewed; the inclusion criterion was the isolation of Sporothrix
      spp. in culture. RESULTS: In total, 2,301 feline cases were identified.
      CONCLUSIONS: These results should alert sanitary authorities to the difficulties
      associated with sporotrichosis control.

PMID- 25075495
TI  - Osteoarticular tuberculosis in an HIV-positive patient: a case report.
AB  - The authors report a case of a 38-year-old HIV-positive woman, with subcutaneous
      nodules on the thoracic region with 3 months of evolution. Clinical, laboratory,
      and epidemiological features were evaluated and associated with apparent damage
      to the T11-T12 vertebrae, identification by imaging tests, positivity in a
      polymerase chain reaction-based test, and reactivity to the Mantoux tuberculin
      skin test (PPD-RT 23). The patient was diagnosed with osteoarticular tuberculosis
      and received treatment for a year, and clinical cure was achieved. 

PMID- 25075497
TI  - Differential diagnosis of ulcers throughout the colon.

PMID- 25075498
TI  - Remarkable facts about the history of the Brazilian Society of Tropical Medicine.

PMID- 25075496
TI  - Uneventful benznidazole treatment of acute Chagas disease during pregnancy: a
      case report.
AB  - This report describes the case of a patient with acute Chagas disease in
      Tocantins, Brazil, who was unaware of her pregnancy during benznidazole
      treatment. She presented with impaired cardiac function during the acute phase
      (pericarditis and incomplete right bundle-branch block) that resolved favorably
      after benznidazole therapy. Serological results also became negative, as
      determined by hemagglutination assays, enzyme-linked immunosorbent assays, and
      immunofluorescence assays. The child was born without sequelae and showed no
      evidence of congenital Trypanosoma cruzi infection at birth or 24 days later. 

PMID- 25075499
TI  - Helicobacter pylori cagE is not associated with clinical outcomes in the
      Kurdistan region of Iraq.

PMID- 25075500
TI  - Authors reply: cagE as a biomarker of the pathogenicity of Helicobacter pylori.

PMID- 25075501
TI  - Blastic plasmacytoid dendritic cell neoplasm: report of a case presenting with
      lung and central nervous system involvement and review of the literature.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic
      malignancy with almost invariably cutaneous involvement and poor prognosis. We
      report a case of BPDCN in a 58-year-old man who presented with skin, lymph node,
      bone marrow, peripheral blood, lung, and central nervous system involvement. To
      the best of our knowledge, central nervous system (CNS) involvement as initial
      presentation has not been reported since the latest World Health Organization
      (WHO) classification of tumors of the hematopoietic and lymphoid tissues in 2008.
      Review of the literature was performed on BPDCN cases published in 2008-2013 in
      PubMed. The major clinical, histopathologic, immunophenotypic, and cytogenetic
      aspects of the disease were discussed. Dermatologists and dermatopathologists
      should be aware of this rare disease for which nearly half of the patients
      present with only cutaneous lesions at diagnosis, as it may allow for early
      diagnosis and appropriate treatment. 

PMID- 25075502
TI  - The supply of hematology/oncology specialists.
AB  - National hematology and oncology organizations and experts in the field, predict
      a shortage of hematology/oncology specialists in the United States. Four types of
      hematology/oncology graduate medical education programs picked to represent
      direct patient care specialists are presented as physician supply in quantitative
      data proportional to the averages of the United States in this paper. The
      hematology/oncology physician production in Louisiana is similar to the average
      of all programs in the United States. The complexities of having several
      hematology/oncology graduate medical education programs, along with other
      specialists, make physician supply more difficult to predict. The patient care
      demand will rise gradually as the population increases and aging of the
      population ensues. Technology proliferates, and reform adds patient numbers. As
      the US shortage of hematology/oncology specialists occurs, the state of Louisiana
      is tracking the United States in supply and will show the shortage in the same
      way, same timing, and for the same reasons. 

PMID- 25075503
TI  - Treatment of submucous cleft palate with selective use of the Furlow Z
      palatoplasty.
AB  - PURPOSE: Submucous cleft is an uncommon entity that can be complicated by
      functional abnormalities, specifically velopharyngeal incompetence (VPI),
      secondary to abnormal palatal muscular insertion. This study aims to characterize
      our experience using the Furlow Z-palatoplasty for the treatment of VPI in
      patients with submucous clefts. METHODS: A retrospective chart review was
      conducted looking at 24 patients diagnosed with symptomatic submucous clefts
      between 2000 and 2007 at Children's Hospital of New Orleans. Demographics such as
      age, gender, diagnosis, need for surgical correction, type of operation,
      complications, presence of genetic syndromes, need for secondary surgery, and
      need for myringotomy tubes were examined. RESULTS: The average age at initial
      surgery for the entire study population was 6.2 years. The success rate of our
      Furlow procedure was 66.7%, with 33.3% requiring secondary pharyngeal flaps. The
      genetic syndromic patient population had an average age at initial surgery of
      four years and experienced a lower primary success rate of 50%. The non-syndromic
      patient population had an average age at initial surgery of 7.3 years, with an
      85.7% primary success rate. CONCLUSIONS: Our data supports the notion that Furlow
      Z-palatoplasty is an effective procedure in the treatment of submucous cleft
      palate with VPI, frequently without the need for secondary surgical procedures in
      the majority of patients, particularly those patients without syndromes.

PMID- 25075504
TI  - Distal ventriculoperitoneal shunt catheter migration to the right ventricle of
      the heart--a case report.
AB  - Ventriculoperitoneal shunts (VPS) have few complications other than mechanical
      obstruction and infection. A VPS catheter located in the chest is a rare
      complication, while intracardiac catheter migration is rarer still. We present a
      case of intracardiac migration of a distal VPS catheter after initial documented
      peritoneal placement. Puncture or erosion of a cervical vein may predispose a
      patient to such a migration. Negative inspiratory pressure and orthograde blood
      flow may then draw the catheter proximally through a vein and eventually to the
      heart or pulmonary artery. We discuss the mechanisms and management of this rare,
      yet dangerous, complication of a routine neurosurgical procedure. 

PMID- 25075505
TI  - Malposition of a hemodialysis catheter in the accessory hemiazygos vein.

PMID- 25075506
TI  - Rapid HIV Testing in a New Orleans Emergency Department is Effective in
      Identifying New HIV Diagnoses and in Linking Patients to Care.
AB  - A retrospective chart review of patients who agreed to a rapid HIV test in the
      emergency department in the initial year of institution of the rapid test was
      conducted. Out of 8,204 patients, 99 were newly diagnosed with HIV in the first
      year of the institution of the rapid HIV test (1.2%). Eighty-five (86%) had a
      documented referral to the infectious disease clinic, and 59 (60%) were linked to
      care within one year of diagnosis. The majority (58%) of the patients with a new
      diagnosis of HIV had been seen in the Interim Louisiana State University Public
      Hospital (ILPH) healthcare system in the five years prior to their diagnosis.
      Forty-nine percent of the patients met diagnostic criteria of AIDS at diagnosis.
      Rapid HIV testing in the emergency department is an effective way to find
      previously undiagnosed patients and link them to subspecialty care. 

PMID- 25075507
TI  - In memoriam: Edward S. Connolly, MD 1934-2014.

PMID- 25075508
TI  - Protecting the Private Practice of Medicine. Louisiana's First Physician-Owned
      Accountable Care Organization: The Inaugural 90 Days.

PMID- 25075509
TI  - ECG of the Month. Amaurosis Fugax in a 45-Year-Old Woman. DIAGNOSIS: Normal sinus
      rhythm; left atrial enlargement.

PMID- 25075511
TI  - Clinical case of the month: altered mental status and headache in a young man.

PMID- 25075510
TI  - Radiology case of the month. Progressive slurring of speech and difficulty
      reading in a 62-year-old male. Final diagnosis: Metastatic small cell cancer of
      the prostate gland.
AB  - A 62-year-old male with controlled hypertension, coronary artery disease, and
      borderline diabetes presented to the emergency room after experiencing a gradual
      one-month progression of slurring of speech and difficulty reading. The patient
      maintained his vital signs throughout his ambulance ride to the hospital and was
      clinically stable at time of arrival to the emergency department. 

PMID- 25075512
TI  - Pathology case of the month. Altered mental status, alcohol abuse, and
      hyperammonemia. DIAGNOSIS: Mallory-Denk bodies (a.k.a. Mallory's hyaline)-seen
      most commonly in alcoholic liver disease.
AB  - A 74-year-old woman with a past medical history of diabetes, hypertension, and
      alcohol abuse was brought to the emergency department and subsequently admitted
      to the intensive care unit with an altered mental status and weakness.
      Laboratories revealed acute renal failure (BUN 15 mg/dL, creatinine 2.5 mg/dL),
      elevated serum transaminase (AST of 83 IU/L), hyperammonemia (187 ug/dL), and
      marked normocytic anemia requiring transfusion of three units of packed red cells
      (hemoglobin 4.3 g/dL; hematocrit 13.1%). Blood ethanol level at the time of
      admission was less than 5 mg/dL, and full urine toxicology was negative. Alcohol
      abuse was reported to consist of, on average, "one pint of gin per day." Her
      hospital course was nine days and included complete inotropic blood pressure
      support and intubation. On the ninth day, she was declared dead, and
      authorization for an unrestricted autopsy was granted by the coroner. At autopsy,
      two liters of serous ascitic fluid was drained from the peritoneal cavity, and
      non-ruptured, distended varices were identified at the gastroesophageal junction.
      Additional findings included changes compatible with hypertensive cardiovascular
      disease, including hypertrophy of the interventricular cardiac septum and
      glomerulosclerosis along with renal atrophy. The liver weighed 1,300 grams
      (normal 1,475 gm+/-362) and was markedly discolored yellow-tan. Its parenchyma
      was more firm than usual. Representative microscopic sections from the decedent's
      liver are shown in the image below.

PMID- 25075513
TI  - Inequality in disability in Bangladesh.
AB  - OBJECTIVE: To investigate inequality in disability in Bangladesh. METHODS: The
      study used both household level and individual level data from a large nationally
      representative data set, Bangladesh's Household Income and Expenditure Survey
      2010. Principal component analysis was used to construct a wealth index based on
      household assets from household level data. Then, using data from 49,809
      individuals aged 5 years and over, chi-square tests and logistic regression were
      performed to test the association between wealth level and disability. FINDINGS:
      Women and older people are significantly more likely to report having
      disabilities than men and younger people. For middle and rich families,
      respectively, there is a 14 percent lower likelihood of reporting disabilities
      than for poor families. Changes in the probability of having disabilities are
      linear with increasing wealth. In addition, the study identifies some significant
      factors affecting disability, namely, age, sex, education, marital status, and
      place of residence including divisional differences. CONCLUSION: In Bangladesh,
      worse health among the poor argues for policies prioritizing this group while at
      the same time giving special attention to women and the elderly.

PMID- 25075514
TI  - Tapping to a slow tempo in the presence of simple and complex meters reveals
      experience-specific biases for processing music.
AB  - Musical meters vary considerably across cultures, yet relatively little is known
      about how culture-specific experience influences metrical processing. In
      Experiment 1, we compared American and Indian listeners' synchronous tapping to
      slow sequences. Inter-tone intervals contained silence or to-be-ignored rhythms
      that were designed to induce a simple meter (familiar to Americans and Indians)
      or a complex meter (familiar only to Indians). A subset of trials contained an
      abrupt switch from one rhythm to another to assess the disruptive effects of
      contradicting the initially implied meter. In the unfilled condition, both groups
      tapped earlier than the target and showed large tap-tone asynchronies (measured
      in relative phase). When inter-tone intervals were filled with simple-meter
      rhythms, American listeners tapped later than targets, but their asynchronies
      were smaller and declined more rapidly. Likewise, asynchronies rose sharply
      following a switch away from simple-meter but not from complex-meter rhythm. By
      contrast, Indian listeners performed similarly across all rhythm types, with
      asynchronies rapidly declining over the course of complex- and simple-meter
      trials. For these listeners, a switch from either simple or complex meter
      increased asynchronies. Experiment 2 tested American listeners but doubled the
      duration of the synchronization phase prior to (and after) the switch. Here,
      compared with simple meters, complex-meter rhythms elicited larger asynchronies
      that declined at a slower rate, however, asynchronies increased after the switch
      for all conditions. Our results provide evidence that ease of meter processing
      depends to a great extent on the amount of experience with specific meters. 

PMID- 25075515
TI  - In vivo confocal microscopy assessment of the corneoscleral limbal stem cell
      niche before and after biopsy for cultivated limbal epithelial transplantation to
      restore corneal epithelium.
AB  - Autologous cultivated limbal epithelial transplantation (CLET) is a successful
      therapy to restore corneal epithelium when limbal epithelial stem cells are
      damaged unilaterally, which can result in corneal blindness. We used in vivo
      confocal microscopy (IVCM) to identify the best location in the corneoscleral
      limbal niche and to harvest autologous epithelial stem cells for CLET. We also
      ascertained the completeness of limbal structure removal after biopsy and
      followed the healing process for any evidence of limbal structure reappearance.
      The 4 meridians of the corneoescleral limbus of 5 healthy donor eyes were scanned
      clinically and by IVCM before biopsy and 1 week, 1, 3, and 6 months after. IVCM
      detected palisades of Vogt, the limbal niche hallmark, more efficiently (100%)
      than clinically (60%), and were consistently better defined at the 12 o'clock
      meridian, and so this was the site selected for biopsy. The depth of palisades
      was 80.4+/-19.8 MUm, and of the limbal biopsies was 136.8+/-19.1 MUm, thus
      assuring that the limbal niche was completely harvested in all cases. Re
      epithelialization of the donor site was complete at 1 week. The limbal wound was
      refilled with fibrovascular tissue, and no limbal-like structures reappeared. The
      study shows that clinical absence of palisades of Vogt is not necessarily an
      exclusionary criterion for autologous CLET. IVCM was useful to select the best
      place for limbal biopsy and identified features not visible clinically. IVCM also
      confirmed complete removal of limbal tissue by the biopsy. Limbal niche
      structures did not reappear by 6 months after surgery.

PMID- 25075516
TI  - Does competition really bring out the worst? Testosterone, social distance and
      inter-male competition shape parochial altruism in human males.
AB  - Parochial altruism, defined as increased ingroup favoritism and heightened
      outgroup hostility, is a widespread feature of human societies that affects
      altruistic cooperation and punishment behavior, particularly in intergroup
      conflicts. Humans tend to protect fellow group members and fight against
      outsiders, even at substantial costs for themselves. Testosterone modulates
      responses to competition and social threat, but its exact role in the context of
      parochial altruism remains controversial. Here, we investigated how testosterone
      influences altruistic punishment tendencies in the presence of an intergroup
      competition. Fifty male soccer fans played an ultimatum game (UG), in which they
      faced anonymous proposers that could either be a fan of the same soccer team
      (ingroup) or were fans of other teams (outgroups) that differed in the degree of
      social distance and enmity to the ingroup. The UG was played in two contexts with
      varying degrees of intergroup rivalry. Our data show that unfair offers were
      rejected more frequently than fair proposals and the frequency of altruistic
      punishment increased with increasing social distance to the outgroups. Adding an
      intergroup competition led to a further escalation of outgroup hostility and
      reduced punishment of unfair ingroup members. High testosterone levels were
      associated with a relatively increased ingroup favoritism and also a change
      towards enhanced outgroup hostility in the intergroup competition. High
      testosterone concentrations further predicted increased proposer generosity in
      interactions with the ingroup. Altogether, a significant relation between
      testosterone and parochial altruism could be demonstrated, but only in the
      presence of an intergroup competition. In human males, testosterone may promote
      group coherence in the face of external threat, even against the urge to
      selfishly maximize personal reward. In that way, our observation refutes the view
      that testosterone generally promotes antisocial behaviors and aggressive
      responses, but underlines its rather specific role in the fine-tuning of male
      social cognition. 

PMID- 25075517
TI  - Molecular epidemiology of influenza A/H3N2 viruses circulating in Mexico from
      2003 to 2012.
AB  - In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003
      and 2012 were studied. Our findings show that different human A/H3N2 viral
      lineages co-circulate within a same season and can also persist locally in
      between different influenza seasons, increasing the chance for genetic
      reassortment events. A novel minor cluster was also identified, named here as
      Korea, that circulated worldwide during 2003. Frequently, phylogenetic
      characterization did not correlate with the determined antigenic identity,
      supporting the need for the use of molecular evolutionary tools additionally to
      antigenic data for the surveillance and characterization of viral diversity
      during each flu season. This work represents the first long-term molecular
      epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete
      genomic sequences and contributes to the monitoring of evolutionary trends of
      A/H3N2 influenza viruses within North and Central America. 

PMID- 25075518
TI  - Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance
      of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like
      activities.
AB  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates the extracellular
      matrix turnover by inhibiting the proteolytic activity of matrix
      metalloproteinases (MMPs). TIMP-1 also displays MMP-independent activities that
      influence the behavior of various cell types including neuronal plasticity, but
      the underlying molecular mechanisms remain mostly unknown. The trans-membrane
      receptor low-density lipoprotein receptor-related protein-1 (LRP-1) consists of a
      large extracellular chain with distinct ligand-binding domains that interact with
      numerous ligands including TIMP-2 and TIMP-3 and a short transmembrane chain with
      intracellular motifs that allow endocytosis and confer signaling properties to
      LRP-1. We addressed TIMP-1 interaction with recombinant ligand-binding domains of
      LRP-1 expressed by CHO cells for endocytosis study, or linked onto sensor chips
      for surface plasmon resonance analysis. Primary cortical neurons bound and
      internalized endogenous TIMP-1 through a mechanism mediated by LRP-1. This
      resulted in inhibition of neurite outgrowth and increased growth cone volume.
      Using a mutated inactive TIMP-1 variant we showed that TIMP-1 effect on neurone
      morphology was independent of its MMP inhibitory activity. We conclude that TIMP
      1 is a new ligand of LRP-1 and we highlight a new example of its MMP-independent,
      cytokine-like functions. 

PMID- 25075520
TI  - Influence of PhoP and intra-species variations on virulence of Yersinia
      pseudotuberculosis during the natural oral infection route.
AB  - The two-component regulatory system PhoP/PhoQ has been shown to (i) control
      expression of virulence-associated traits, (ii) confer survival and growth within
      macrophages and (iii) play a role in Yersinia infections. However, the influence
      of PhoP on virulence varied greatly between different murine models of infection
      and its role in natural oral infections with frequently used representative
      isolates of Y. pseudotuberculosis was unknown. To address this issue, we
      constructed an isogenic set of phoP+ and phoP- variants of strain IP32953 and
      YPIII and analyzed the impact of PhoP using in vitro functionality experiments
      and a murine oral infection model, whereby we tested for bacterial dissemination
      and influence on the host immune response. Our results revealed that PhoP has a
      low impact on virulence, lymphatic and systemic organ colonization, and on immune
      response modulation by IP32953 and YPIII, indicating that PhoP is not absolutely
      essential for oral infections but may be involved in fine-tuning the outcome. Our
      work further revealed certain strain-specific differences in virulence
      properties, which do not strongly rely on the function of PhoP, but affect tissue
      colonization, dissemination and/or persistence of the bacteria. Highlighted intra
      species variations may provide a potential means to rapidly adjust to
      environmental changes inside and outside of the host. 

PMID- 25075521
TI  - The transaldolase, a novel allergen of Fusarium proliferatum, demonstrates IgE
      cross-reactivity with its human analogue.
AB  - Fusarium species are among airborne fungi and recognized as causative agents of
      human atopic disorders. However, Fusarium allergens have not been well
      characterized and the lack of information limits clinical diagnosis and treatment
      of fungal allergy. The purpose of this study is to identify and characterize
      important allergens of F. proliferatum. IgE-reacting F. proliferatum components
      were identified by immunoblot using serum samples from patients of respiratory
      atopic diseases. Characterization of allergens and determination of IgE cross
      reactivity were performed by cDNA cloning, then homologous expression and
      immunoblot inhibition studies. We identified nine different F. proliferatum
      components that can be recognized by IgE antibodies in 17 (28%) of the 60 atopic
      sera tested. Components with molecular masses of about 43, 37.5 and 36.5 kDa with
      IgE-binding frequencies of about 88, 47 and 53%, respectively, were considered as
      important allergens of F. proliferatum. The 37.5 kDa IgE-binding component was
      putatively considered as a transaldolase protein of F. proliferatum. The full
      length cDNA of F. proliferatum transaldolase was subsequently cloned. It encodes
      an open reading frame of 312 amino acids and has sequence identifies of 73 and
      61%, respectively, with Cladosporium and human transaldolases. The purified
      recombinant F. proliferatum transaldolase can inhibit the IgE-binding against the
      37.5 kDa component of F. proliferatum and the transaldolase allergen from
      Cladosporium cladosporioides. More importantly, the recombinant F. proliferatum
      transaldolase can inhibit IgE-binding against human transaldolase in a
      concentration-dependent manner. Thus, a novel and important F. proliferatum
      transaldolase allergen was identified. In addition to IgE cross-reactivity
      between the Fusarium and the Cladosporium transaldolase allergens, IgE cross
      reactivity between the Fusarium and the human transaldolases also exists and
      might contribute to atopic manifestations in the absence of exogenous allergen
      exposure. 

PMID- 25075522
TI  - NAC attenuates LPS-induced toxicity in aspirin-sensitized mouse macrophages via
      suppression of oxidative stress and mitochondrial dysfunction.
AB  - Bacterial endotoxin lipopolysaccharide (LPS) induces the production of
      inflammatory cytokines and reactive oxygen species (ROS) under in vivo and in
      vitro conditions. Acetylsalicylic acid (ASA, aspirin) is a commonly used anti
      inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC),
      an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages
      treated with LPS. We investigated the effects of LPS alone and in conjunction
      with a sub-toxic concentration of ASA, on metabolic and oxidative stress,
      apoptosis, and mitochondrial function using J774.2 mouse macrophage cell line.
      Protection from LPS-induced toxicity by NAC was also studied. LPS alone markedly
      induced ROS production and oxidative stress in macrophage cells. When ASA was
      added to LPS-treated macrophages, the increase in oxidative stress was
      significantly higher than that with LPS alone. Similarly, alteration in
      glutathione-dependent redox metabolism was also observed in macrophages after
      treatment with LPS and ASA. The combination of LPS and ASA selectively altered
      the CYP 3A4, CYP 2E1 and CYP 1A1 catalytic activities. Mitochondrial respiratory
      complexes and ATP production were also inhibited by LPS-ASA treatment.
      Furthermore a higher apoptotic cell death was also observed in LPS-ASA treated
      macrophages. NAC pre-treatment showed protection against oxidative stress induced
      apoptosis and mitochondrial dysfunction. These effects are presumed, at least in
      part, to be associated with alterations in NF-kappaB/Nrf-2 mediated cell
      signaling. These results suggest that macrophages are more sensitive to LPS when
      challenged with ASA and that NAC pre-treatment protects the macrophages from
      these deleterious effects.

PMID- 25075524
TI  - Selected papers from The 7th IEEE international conference on systems Biology
      (ISB 2013).

PMID- 25075523
TI  - MDSCs mediate angiogenesis and predispose canine mammary tumor cells for
      metastasis via IL-28/IL-28RA (IFN-lambda) signaling.
AB  - BACKGROUND: Myeloid-derived suppressor cells (MDSCs) function in
      immunosuppression and tumor development by induction of angiogenesis in a STAT3
      dependent manner. Knowledge of MDSC biology is mainly limited to mice studies,
      and more clinical investigations using spontaneous tumor models are required.
      Here we performed in vitro experiments and clinical data analysis obtained from
      canine patients. METHODS: Using microarrays we examined changes in gene
      expression in canine mammary cancer cells due to their co-culture with MDSCs.
      Further, using Real-time rt-PCR, Western blot, IHC, siRNA, angiogenesis assay and
      migration/invasion tests we examined a role of the most important signaling
      pathway. RESULTS: In dogs with mammary cancer, the number of circulating MDSCs
      increases with tumor clinical stage. Microarray analysis revealed that MDSCs had
      significantly altered molecular pathways in tumor cells in vitro. Particularly
      important was the detected increased activation of IL-28/IL-28RA (IFN-lambda)
      signaling. The highest expression of IL-28 was observed in stage III/IV mammary
      tumor-bearing dogs. IL-28 secreted by MDSCs stimulates STAT3 in tumor cells,
      which results in increased expression of angiogenic factors and subsequent
      induction of angiogenesis by endothelial cells, epithelial-mesenchymal transition
      (EMT) and increased migration of tumor cells in vitro. Knockdown of IL-28RA
      decreased angiogenesis, tumor cell invasion and migration. CONCLUSIONS: We showed
      for the first time that MDSCs secrete IL-28 (IFN-lambda), which promotes
      angiogenesis, EMT, invasion and migration of tumor cells. Thus, IL-28 may
      constitute an interesting target for further therapies. Moreover, the similarity
      in circulating MDSC levels at various tumor clinical stages between canine and
      human patients indicates canines as a good model for clinical trials of drugs
      targeting MDSCs.

PMID- 25075525
TI  - Cell commitment motif composed of progenitor-specific transcription factors and
      mutual-inhibition regulation.
AB  - Simple mutual-inhibition networks are frequently occurring motifs in
      transcriptional regulatory networks for cell lineage commitment. Stable
      attractors represent cell commitment states. However, how progenitor-specific
      transcription factors stabilise progenitor cells and commit them to different
      cell fates remains unexplained. In this study, the authors represent the cell
      commitment motifs composed of mutual-inhibition regulation and progenitor
      specific transcription factors, and develop associated mathematical model to
      understand how specific cell fate decisions are made. Bifurcation analysis and
      numerical simulation show that the model could exhibit multiple stable steady
      states corresponding to progenitor and committed cell states. The transitions
      between different cell states correspond to different commitment processes.
      Furthermore, the authors demonstrate that different commitment patterns, for
      example, haematopoietic and neural fate decisions fall within the scope of
      proposed framework. 

PMID- 25075526
TI  - Overshoot in biological systems modelled by Markov chains: a non-equilibrium
      dynamic phenomenon.
AB  - A number of biological systems can be modelled by Markov chains. Recently, there
      has been an increasing concern about when biological systems modelled by Markov
      chains will perform a dynamic phenomenon called overshoot. In this study, the
      authors found that the steady-state behaviour of the system will have a great
      effect on the occurrence of overshoot. They showed that overshoot in general
      cannot occur in systems that will finally approach an equilibrium steady state.
      They further classified overshoot into two types, named as simple overshoot and
      oscillating overshoot. They showed that except for extreme cases, oscillating
      overshoot will occur if the system is far from equilibrium. All these results
      clearly show that overshoot is a non-equilibrium dynamic phenomenon with energy
      consumption. In addition, the main result in this study is validated with real
      experimental data. 

PMID- 25075527
TI  - Comparative genomic and transcriptomic analysis of terpene synthases in
      Arabidopsis and Medicago.
AB  - This study provides a timely comparative genomic and transcriptomic analysis of
      the terpene synthase (TPS) gene family in Medicago truncatula (bears glandular
      and non-glandular trichomes) and Arabidopsis thaliana (bears non-glandular
      trichomes). The authors' efforts aimed to gain insight into TPS function,
      phylogenetic relationships and the role of trichomes in terpene biosynthesis and
      function. In silico analysis identified 33 and 23 putative full-length TPS genes
      in Arabidopsis and Medicago, respectively. All AtTPS and MtTPS fall into the five
      established angiosperm TPS subfamilies, with lineage-specific expansion of
      Subfamily A in Arabidopsis and Subfamily G in Medicago. Large amounts of tandem
      duplication have occurred in both species, but only one syntenic duplication
      seems to have occurred in Arabidopsis, with no such duplication apparent in
      Medicago. Expression analysis indicates that there is much more trichome
      localised TPS expression in Medicago than in Arabidopsis. However, TPS genes were
      expressed in non-glandular trichomes in both species. One trichome-specific gene
      has been identified in each Medicago and Arabidopsis along with flower-, seed-,
      stem- and root-specific genes. Of these, MtTPS11 is a promising candidate for
      trichome-specific genetic engineering, a technology that may be possible for both
      plants according to the findings of this manuscript. These results suggest that
      non-glandular trichomes may play a role in plant chemical defense and/or
      ecological communication instead of only in physical defence. Finally, the
      general lack of correlation between expression patterns and phylogenetic
      relationships in both species suggests that phylogenetic analysis alone is
      insufficient to predict gene function even for phylogenetically close paralogs. 

PMID- 25075528
TI  - Systematic study on G-protein couple receptor prototypes: did they really evolve
      from prokaryotic genes?
AB  - G-protein couple receptor (GPCR) is one of the most striking examples of
      signalling proteins and it is only observed in eukaryotes. Based on various GPCR
      identification methods and classification systems, several evolutionary
      presumptions of different GPCR families have been reported. However, the
      prototype of GPCR still limits our knowledge. By investigating its structure and
      domain variance, the authors propose that GPCR might be evolved from prokaryotic
      world. The results given by the authors indicate that metabotropic glutamate
      receptor family would be the ancestor of GPCR. Phylogenetic analysis hints that
      one of metabotropic glutamate receptor GABA is possibly formed and evolved from
      the ancient chemical union of bacteriorhodopsin and periplasmic binding protein.
      The results obtained by the authors also unprecedentedly demonstrate that
      specific domains and identical structures are shown in each type of GPCR, which
      provides unique opportunities for future strategies on GPCR orphans' prediction
      and classification. 

PMID- 25075529
TI  - Knowledge discovery for pancreatic cancer using inductive logic programming.
AB  - Pancreatic cancer is a devastating disease and predicting the status of the
      patients becomes an important and urgent issue. The authors explore the
      applicability of inductive logic programming (ILP) method in the disease and show
      that the accumulated clinical laboratory data can be used to predict disease
      characteristics, and this will contribute to the selection of therapeutic
      modalities of pancreatic cancer. The availability of a large amount of clinical
      laboratory data provides clues to aid in the knowledge discovery of diseases. In
      predicting the differentiation of tumour and the status of lymph node metastasis
      in pancreatic cancer, using the ILP model, three rules are developed that are
      consistent with descriptions in the literature. The rules that are identified are
      useful to detect the differentiation of tumour and the status of lymph node
      metastasis in pancreatic cancer and therefore contributed significantly to the
      decision of therapeutic strategies. In addition, the proposed method is compared
      with the other typical classification techniques and the results further confirm
      the superiority and merit of the proposed method. 

PMID- 25075530
TI  - Key network approach reveals new insight into Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a severe neurodegenerative disorder without curative
      treatment. Extensive data on pathological molecular processes have been
      accumulated over the last years. These data combined allows a systems biology
      approach to identify key regulatory elements of AD and to establish a model
      descriptive of the disease process which can be used for the development of
      therapeutic agents. In this study, the authors propose a closed network that uses
      a set of nodes (amyloid beta, tau, beta-secretase, glutamate, cyclin-dependent
      kinase 5, phosphoinositide 3-kinase and hypoxia-induced factor 1 alpha) as key
      elements of importance to the pathogenesis of AD. The proposed network, in total
      39 nodes, is able to become a novel tool capable of providing new insights into
      AD, such as feedback loops. Further, it highlights interconnections between
      pathways and identifies their combination for therapy of AD. 

PMID- 25075531
TI  - Analysis and classification of DNA-binding sites in single-stranded and double
      stranded DNA-binding proteins using protein information.
AB  - Single-stranded DNA-binding proteins (SSBs) and double-stranded DNA-binding
      proteins (DSBs) play different roles in biological processes when they bind to
      single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA). However, the
      underlying binding mechanisms of SSBs and DSBs have not yet been fully
      understood. Here, the authors firstly constructed two groups of ssDNA and dsDNA
      specific binding sites from two non-redundant sets of SSBs and DSBs. They further
      analysed the relationship between the two classes of binding sites and a newly
      proposed set of features (residue charge distribution, secondary structure and
      spatial shape). To assess and utilise the predictive power of these features,
      they trained a classification model using support vector machine to make
      predictions about the ssDNA and the dsDNA binding sites. The author's analysis
      and prediction results indicated that the two classes of binding sites can be
      distinguishable by the three types of features, and the final classifier using
      all the features achieved satisfactory performance. In conclusion, the proposed
      features will deepen their understanding of the specificity of proteins which
      bind to ssDNA or dsDNA. 

PMID- 25075532
TI  - Prediction of hot spots in protein interfaces using extreme learning machines
      with the information of spatial neighbour residues.
AB  - The identification of hot spots, a small subset of protein interfaces that
      accounts for the majority of binding free energy, is becoming increasingly
      important for the research on protein-protein interaction and drug design. For
      each interface residue or target residue to be predicted, the authors extract
      hybrid features which incorporate a wide range of information of the target
      residue and its spatial neighbor residues, that is, the nearest contact residue
      in the other face (mirror-contact residue) and the nearest contact residue in the
      same face (intra-contact residue). Here, feature selection is performed using
      random forests to avoid over-fitting. Thereafter, the extreme learning machine is
      employed to effectively integrate these hybrid features for predicting hot spots
      in protein interfaces. By the 5-fold cross validation in the training set, their
      method can achieve accuracy (ACC) of 82.1% and Matthew's correlation coefficient
      (MCC) of 0.459, and outperforms some alternative machine learning methods in the
      comparison study. Furthermore, their method achieves ACC of 76.8% and MCC of
      0.401 in the independent test set, and is more effective than the major existing
      hot spot predictors. Their prediction method offers a powerful tool for
      uncovering candidate residues in the studies of alanine scanning mutagenesis for
      functional protein interaction sites. 

PMID- 25075533
TI  - Register-based predictors of violations of animal welfare legislation in dairy
      herds.
AB  - The assessment of animal welfare can include resource-based or animal-based
      measures. Official animal welfare inspections in Denmark primarily control
      compliance with animal welfare legislation based on resource measures (e.g.
      housing system) and usually do not regard animal response parameters (e.g.
      clinical and behavioural observations). Herds selected for welfare inspections
      are sampled by a risk-based strategy based on existing register data. The aim of
      the present study was to evaluate register data variables as predictors of dairy
      herds with violations of the animal welfare legislation (VoAWL) defined as
      occurrence of at least one of the two most frequently violated measures found at
      recent inspections in Denmark, namely (a) presence of injured animals not
      separated from the rest of the group and/or (b) animals in a condition warranting
      euthanasia still being present in the herd. A total of 25 variables were
      extracted from the Danish Cattle Database and assessed as predictors using a
      multivariable logistic analysis of a data set including 73 Danish dairy herds,
      which all had more than 100 cows and cubicle loose-housing systems. Univariable
      screening was used to identify variables associated with VoAWL at a P-value<0.2
      for the inclusion in a multivariable logistic regression analysis. Backward
      selection procedures identified the following variables for the final model
      predictive of VoAWL: increasing standard deviation of milk yield for first
      lactation cows, high bulk tank somatic cell count (?250 000 cells/ml) and
      suspiciously low number of recorded veterinary treatments (?25 treatments/100 cow
      years). The identified predictors may be explained by underlying management
      factors leading to impaired animal welfare in the herd, such as poor hygiene,
      feeding and management of dry or calving cows and sick animals. However, further
      investigations are required for causal inferences to be established.

PMID- 25075534
TI  - Relationship between 24 h urinary potassium and diet quality in the adult Spanish
      population.
AB  - OBJECTIVE: To study the relationship between diet quality and 24 h urinary K
      excretion. DESIGN: K was measured in 24 h urine samples, while diet was studied
      using a 24 h recall method over two consecutive days. Diet quality was determined
      using the Healthy Eating Index (HEI). The body weight, height and body
      composition of all participants were recorded, and the BMI of each calculated.
      SETTING: Representative members of the adult Spanish population from the FANPE
      Study ('Fuentes Alimentarias de Nutrientes en Poblacion Espanola'; Dietary
      Sources of Nutrients in the Spanish Population). SUBJECTS: The final sample size
      was 329 participants aged 18-60 years. RESULTS: Participants with a 24 h urinary
      K excretion >= 93 mmol/d (group AP = adequate potassium) had greater self
      reported K intakes, consumed more fruit and vegetables, had a more varied diet
      and had better HEI scores than those with a 24 h urinary K excretion <93 mmol/d
      (group IP = inadequate potassium). A significant positive correlation was seen
      between 24 h urinary K and dietary variety and the number of servings of fruits,
      vegetables and dairy products consumed, and between each of these and the HEI
      after correcting for age, sex, BMI, coefficient of activity, energy intake and
      the under-reporting of energy intake. AP participants were less likely to have an
      inadequate diet (HEI score <50) than IP participants (OR =0.439; 95 % CI 0.201,
      0.961; P=0.039). CONCLUSIONS: Diet quality, measured by the HEI, is correlated
      with 24 h urinary K excretion in Spanish adults.

PMID- 25075536
TI  - Isolation of contractile cardiomyocytes from human pluripotent stem-cell-derived
      cardiomyogenic cultures using a human NCX1-EGFP reporter.
AB  - The prospective isolation of defined contractile human pluripotent stem cell
      (hPSC)-derived cardiomyocytes is advantageous for regenerative medicine and drug
      screening applications. Currently, enrichment of cardiomyocyte populations from
      such cultures can be achieved by combinations of cell surface markers or the
      labor-intensive genetic modification of cardiac developmental genes, such as
      NKX2.5 or MYH6, with fluorescent reporters. To create a facile, portable method
      for the isolation of contractile cardiomyocytes from cardiomyogenic hPSC
      cultures, we employed a highly conserved cardiac enhancer sequence in the SLC8A1
      (NCX1) gene to generate a lentivirally deliverable, antibiotic-selectable NCX1cp
      EGFP reporter. We show that human embryonic stem cells (and induced pluripotent
      stem cells) transduced with the NCX1cp-EGFP reporter cassette exhibit enhanced
      green fluorescent protein (EGFP) expression in cardiac progenitors from 5 days
      into the directed cardiac hPSC differentiation protocol, with all reporter
      positive cells transitioning to spontaneously contracting foci 3 days later. In
      subsequent stages of cardiomyocyte maturation, NCX1cp-EGFP expression was
      exclusively limited to contractile cells expressing high levels of cardiac
      troponin T (CTNT), MLC2a/v, and alpha-actinin proteins, and was not present in
      CD90/THY1(+) cardiac stromal cells or CD31/PECAM(+) endothelial cells. Flow
      assisted cytometrically sorted EGFP(+) fractions of differentiated cultures were
      highly enriched in both early (NKX2.5 and TBX5) and late (CTNT/TNNI2, MYH6, MYH7,
      NPPA, and MYL2) cardiomyocyte markers, with a significant proportion of cells
      displaying a ventricular-like action potential pattern in patch-clamp recordings.
      We conclude that the use of the cardiac-specific promoter of the human
      SLC8A1(NCX1) gene is an effective strategy to isolate contractile cardiac cells
      and their progenitors from hPSC-derived cardiomyogenic cultures. 

PMID- 25075535
TI  - Diabetes and cognitive outcomes in a nationally representative sample: the
      National Health and Aging Trends Study.
AB  - BACKGROUND: The prevalence of both type II diabetes mellitus (DM) and cognitive
      impairment is high and increasing in older adults. We examined the extent to
      which DM diagnosis was associated with poorer cognitive performance and dementia
      diagnosis in a population-based cohort of US older adults. METHODS: We studied
      7,606 participants in the National Health and Aging Trends Study, a nationally
      representative cohort of Medicare beneficiaries aged 65 years and older. DM and
      dementia diagnosis were based on self-report from participants or proxy
      respondents, and participants completed a word-list memory test, the Clock
      Drawing Test, and gave a subjective assessment of their own memory. RESULTS: In
      unadjusted analyses, self-reported DM diagnosis was associated with poorer
      immediate and delayed word recall, worse performance on the Clock Drawing Test,
      and poorer self-rated memory. After adjusting for demographic characteristics,
      body mass index, depression and anxiety symptoms, and medical conditions, DM was
      associated with poorer immediate and delayed word recall and poorer self-rated
      memory, but not with the Clock Drawing Test performance or self-reported dementia
      diagnosis. After excluding participants with a history of stroke, DM diagnosis
      was associated with poorer immediate and delayed word recall and the Clock
      Drawing Test performance, and poorer self-rated memory, but not with self
      reported dementia diagnosis. CONCLUSIONS: In this recent representative sample of
      older Medicare enrollees, self-reported DM was associated with poorer cognitive
      test performance. Findings provide further support for DM as a potential risk
      factor for poor cognitive outcomes. Studies are needed that investigate whether
      DM treatment prevents cognitive decline.

PMID- 25075538
TI  - Bovine tuberculosis in a wild boar (Sus scrofa) in Poland.
AB  - Poland is officially tuberculosis free and bovine tuberculosis (BTB) cases are
      rarely found except in bovids. We found BTB in a wild boar (Sus scrofa) in the
      Bieszczady Mountains, southeastern Poland. Studies suggest possible transmission
      of infection between free-living European bison (Bison bonasus caucasicus) and
      wild boar in this area.

PMID- 25075539
TI  - Preliminary investigation of bottlenose dolphins (Tursiops truncatus) for hfe
      gene-related hemochromatosis.
AB  - Hemochromatosis (iron storage disease) has been reported in diverse mammals
      including bottlenose dolphins (Tursiops truncatus). The primary cause of
      excessive iron storage in humans is hereditary hemochromatosis. Most human
      hereditary hemochromatosis cases (up to 90%) are caused by a point mutation in
      the hfe gene, resulting in a C282Y substitution leading to iron accumulation. To
      evaluate the possibility of a hereditary hemochromatosis-like genetic
      predisposition in dolphins, we sequenced the bottlenose dolphin hfe gene, using
      reverse transcriptase-PCR and hfe primers designed from the dolphin genome, from
      liver of affected and healthy control dolphins. Sample size included two case
      animals and five control animals. Although isotype diversity was evident, no
      coding differences were identified in the hfe gene between any of the animals
      examined. Because our sample size was small, we cannot exclude the possibility
      that hemochromatosis in dolphins is due to a coding mutation in the hfe gene.
      Other potential causes of hemochromatosis, including mutations in different
      genes, diet, primary liver disease, and insulin resistance, should be evaluated.

PMID- 25075540
TI  - Serosurvey for selected pathogens in free-ranging American black bears (Ursus
      americanus) in Maryland, USA.
AB  - American black bears (Ursus americanus) in Maryland, USA, live in forested areas
      in close proximity to humans and their domestic pets. From 1999 to 2011, we
      collected 84 serum samples from 63 black bears (18 males; 45 females) in five
      Maryland counties and tested them for exposure to infectious, including zoonotic,
      pathogens. A large portion of the bears had antibody to canine distemper virus
      and Toxoplasma gondii, many at high titers. Prevalences of antibodies to zoonotic
      agents such as rabies virus and to infectious agents of carnivores including
      canine adenovirus and canine parvovirus were lower. Bears also had antibodies to
      vector-borne pathogens common to bears and humans such as West Nile virus,
      Borrelia burgdorferi, Rickettsia rickettsii, and Anaplasma phagocytophilum.
      Antibodies were detected to Leptospira interrogans serovars Pomona,
      Icterohaemorrhagiae, Canicola, Grippotyphosa, and Bratislava. We did not detect
      antibodies to Brucella canis or Ehrlichia canis. Although this population of
      Maryland black bears demonstrated exposure to multiple pathogens of concern for
      humans and domesticated animals, the low levels of clinical disease in this and
      other free-ranging black bear populations indicate the black bear is likely a
      spillover host for the majority of pathogens studied. Nevertheless, bear
      populations living at the human-domestic-wildlife interface with increasing human
      and domestic animal exposure should continue to be monitored because this
      population likely serves as a useful sentinel of ecosystem health.

PMID- 25075541
TI  - Effects of temperature and pH on the persistence of avian paramyxovirus-1 in
      water.
AB  - We evaluated the duration of infectivity of two isolates of avian paramyxovirus-1
      using a model distilled water system. Both viruses remained infective for
      extended periods with 1-log10 reduction times ranging from 370 (4 C) to 6 (37 C)
      days. Minimal effects related to pH (5.4-8.4 at 28 C) were observed.

PMID- 25075542
TI  - Extended-spectrum beta-lactamase-producing Enterobacteriaceae isolated from feces
      of Falconidae, Accipitridae, and Laridae in bird rescue centers in Belgium.
AB  - The presence of extended-spectrum beta-lactamase- and Klebsiella pneumoniae
      carbapenemase-producing Enterobacteriaceae was investigated in feces and in
      choanal and cloacal swabs of birds in rescue centers. Ceftiofur-resistant
      Escherichia coli and Citrobacter freundii were isolated from feces of birds of
      prey (12% positive) and a group of gulls. The genes blaCTX-M-1, blaCTX-M-15, and
      blaCTX-M-32 coded for resistance.

PMID- 25075543
TI  - Perspectives in pediatric pathology: chapter 2. Testicular descent.

PMID- 25075544
TI  - Phytochemical relationship of Euphorbia helioscopia and Euphorbia pulcherrima
      with Lactuca sativa.
AB  - Allelopathy is an important phenomenon that modifies the ecosystem. A plant can
      enhance or reduce the growth of other plant due to the presence of a number of
      allelochemicals in its different parts. Euphorbia helioscopia and Euphorbia
      pulcherrima are medicinal plant species. Both these species are collected from
      wild resources for various purposes. To reduce the pressure on wild population,
      it is important to bring them into cultivation. Therefore, the allelopathic
      effects of E. helioscopia and E. pulcherrima on the growth of lettuce seeds were
      studied. Three different concentrations (2%, 4% and 6%) of five different
      solvents (methanol, acetone, ethyl acetate, n-hexane and distilled water) were
      used to estimate the allelopathic potential of the above-mentioned Euphorbia
      species. Results indicated a non-significant growth inhibitory effect of both
      plants on lettuce seeds. Different extracts reduced the growth of test plant to
      some extent but this inhibition was not significant. From the observed results,
      it was concluded that the studied Euphorbia species, being medicinally important
      crops, can be introduced as intercrop with other cash crops. 

PMID- 25075545
TI  - Mucosal environmental sensors in the pathogenesis of dry eye.
AB  - The 4th Cullen Symposium, held April 17 and 18, 2014, included expert researchers
      in mucosal immunity of the eye and other mucosal surfaces, particularly the gut.
      The theme of the meeting was environmental sensing mechanisms in mucosal tissues
      and their relevance for initiating ocular surface inflammation in dry eye. There
      are a number of shared features between the ocular surface and other mucosal
      surfaces, but distinct differences may exist in the type and distribution of
      mucins and microbiota. Mechanisms to regulate DC maturation and prevent tissue
      damaging inflammation are shared among these sites. Epithelial and dendritic
      cells are key environmental sensors participating in initiation of innate and
      adaptive immune responses in response to a variety of environmental stresses.

PMID- 25075546
TI  - Spatial-temporal variations in carbon dioxide levels in Ibadan, Nigeria.
AB  - Growing evidence suggests how global background levels of atmospheric carbon
      dioxide (CO2) are increasing and this impacts environmental quality and human and
      ecological health. Data from less developed countries are sparse. We determined
      spatial and temporal variations in concentrations of CO2 in selected locations in
      Ibadan, Nigeria with identifiable prominent outdoor sources. Activity driven
      areas in north and south-west areas were identified and marked with a global
      positioning system. Waste management practices and activities generating CO2 were
      documented and described using a technician observation checklist. CO2 levels
      were measured using a portable TELAIRE 7001 attached to HOBO U12 data loggers
      across seasons. Mean CO2 levels were compared over seasons, i.e. rainy season
      months and the dry season months. While CO2 levels recorded outdoors in study
      areas were comparable to available international data, routine monitoring is
      recommended to further characterize concurrent pollutants in fossil fuel
      combustion emissions with known deleterious health effects. 

PMID- 25075547
TI  - MALDI MS in-source decay of glycans using a glutathione-capped iron oxide
      nanoparticle matrix.
AB  - A new matrix-assisted laser desorption ionization (MALDI) mass spectrometry
      matrix is proposed for molecular mass and structural determination of glycans.
      This matrix contains an iron oxide nanoparticle (NP) core with gluthathione (GSH)
      molecules covalently bound to the surface. As demonstrated for the monosaccharide
      glucose and several larger glycans, the mass spectra exhibit good analyte ion
      intensities and signal-to-noise ratios, as well as an exceptionally clean
      background in the low mass-to-charge (m/z) region. In addition, abundant in
      source decay (ISD) occurs when the laser power is increased above the ionization
      threshold; this indicates that the matrix provides strong energy transfer to the
      sample. For five model glycans, ISD produced extensive glycosidic and cross-ring
      cleavages in the positive ion mode from singly charged precursor ions with bound
      sodium ions. Linear, branched, and cyclic glycans were employed, and all were
      found to undergo abundant fragmentation by ISD. (18)O labeling was used to
      clarify m/z assignment ambiguities and showed that the majority of the
      fragmentation originates from the nonreducing ends of the glycans. Studies with a
      peracetylated glycan indicated that abundant ISD fragmentation occurs even in the
      absence of hydroxyl groups. The ISD product ions generated using this new matrix
      should prove useful in the sequencing of glycans. 

PMID- 25075548
TI  - Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and
      drug molecules for image-guided drug delivery and photodynamic therapy.
AB  - A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated
      polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer
      and drug carrier for combined photodynamic and chemotherapy. The amphiphilic
      brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous
      media with hydrophobic conjugated polyelectrolyte backbone as the core and
      hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm,
      with the absorption and emission maxima at 502 and 598 nm, respectively, making
      them suitable for bioimaging applications. Moreover, the CPE itself can serve as
      a photosensitizer, which makes the NPs not only a carrier for drug but also a
      photosensitizing unit for photodynamic therapy, resulting in the combination of
      chemo- and photodynamic therapy for cancer. The half-maximal inhibitory
      concentration (IC50) value for the combination therapy to U87-MG cells is 12.7
      MUg mL(-1), which is much lower than that for the solely photodynamic therapy
      (25.5 MUg mL(-1)) or chemotherapy (132.8 MUg mL(-1)). To improve the tumor
      specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD)
      tripeptide as the receptor to integrin alphavbeta3 overexpressed cancer cells was
      further incorporated to the surface of the NPs. The delivery system based on
      PEGylated CPE is easy to fabricate, which integrates the merits of targeted
      cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy,
      making it promising for cancer treatment. 

PMID- 25075549
TI  - Determination of saffron quality by high-performance liquid chromatography.
AB  - The aim of this work was to propose a high-performance liquid chromatography with
      diode array detection (HPLC-DAD) method for determining the three main compounds
      responsible for determining the quality of saffron (crocetin esters, picrocrocin,
      and safranal) by preparing an aqueous extract according to the ISO 3632 standard
      to solve the difficulty that this standard has for aroma and taste determination
      by ultraviolet-visible spectroscopy. Toward this aim, laboratory-isolated
      picrocrocin, a safranal standard with a purity of >= 88%, trans-crocetin di(beta
      D-gentiobiosyl) ester (trans-4-GG) and trans-crocetin (beta-D-glucosyl)-(beta-D
      gentiobiosyl) ester (trans-3-Gg) standards, both with a purity of >= 99%, and 50
      different saffron spice samples from Italy, Iran, Greece, and Spain were used in
      the intralaboratory validation of the HPLC method. The analytical method proposed
      was adequate in terms of linearity, selectivity, sensitivity, and accuracy for
      determining the three foremost parameters that define the quality of saffron
      using only a saffron solution prepared according to the ISO 3632 standard.

PMID- 25075550
TI  - Gold nanocluster-catalyzed semihydrogenation: a unique activation pathway for
      terminal alkynes.
AB  - We report high catalytic activity of ultrasmall spherical Au25(SC2H4Ph)18 and rod
      shaped Au25(PPh3)10(C=CPh)5X2 (X = Br, Cl) nanoclusters supported on oxides for
      the semihydrogenation of terminal alkynes into alkenes with >99% conversion of
      alkynes and ~100% selectivity for alkenes. In contrast, internal alkynes cannot
      be catalyzed by such "ligand-on" Au25 catalysts; however, with "ligand-off" Au25
      catalysts the internal alkynes can undergo semihydrogenation to yield Z-alkenes,
      similar to conventional gold nanoparticle catalysts. On the basis of the results,
      a unique activation pathway of terminal alkynes by "ligand-on" gold nanoclusters
      is identified, which should follow a deprotonation activation pathway via a R'
      C=C-[AunLm] (where L represents the protecting ligands on the cluster), in
      contrast with the activation mechanism on conventional gold nanocatalysts. This
      new activation mode is supported by observing the incorporation of deprotonated 
      C=CPh as ligands on rod-shaped Au25(PPh3)10(C=CPh)5X2 nanoclusters under
      conditions similar to the catalytic reaction and by detecting the R'-C=C
      [Aun(SC2H4Ph)m] via FT-IR spectroscopy. 

PMID- 25075552
TI  - Nanostructured ultrafast silicon-tip optical field-emitter arrays.
AB  - Femtosecond ultrabright electron sources with spatially structured emission are
      an enabling technology for free-electron lasers, compact coherent X-ray sources,
      electron diffractive imaging, and attosecond science. In this work, we report the
      design, modeling, fabrication, and experimental characterization of a novel
      ultrafast optical field emission cathode comprised of a large (>100,000 tips),
      dense (4.6 million tips.cm(-2)), and highly uniform (<1 nm tip radius deviation)
      array of nanosharp high-aspect-ratio silicon columns. Such field emitters offer
      an attractive alternative to UV photocathodes while providing a direct means of
      structuring the emitted electron beam. Detailed measurements and simulations show
      pC electron bunches can be generated in the multiphoton and tunneling regime
      within a single optical cycle, enabling significant advances in electron
      diffractive imaging and coherent X-ray sources on a subfemtosecond time scale,
      not possible before. At high charge emission yields, a slow rollover in charge is
      explained as a combination of the onset of tunneling emission and the formation
      of a virtual cathode.

PMID- 25075551
TI  - Compromised structure and function of HDAC8 mutants identified in Cornelia de
      Lange Syndrome spectrum disorders.
AB  - Cornelia de Lange Syndrome (CdLS) is a multiple congenital anomaly disorder
      resulting from mutations in genes that encode the core components of the cohesin
      complex, SMC1A, SMC3, and RAD21, or two of its regulatory proteins, NIPBL and
      HDAC8. HDAC8 is the human SMC3 lysine deacetylase required for cohesin recycling
      in the cell cycle. To date, 16 different missense mutations in HDAC8 have
      recently been identified in children diagnosed with CdLS. To understand the
      molecular effects of these mutations in causing CdLS and overlapping phenotypes,
      we have fully characterized the structure and function of five HDAC8 mutants:
      C153F, A188T, I243N, T311M, and H334R. X-ray crystal structures reveal that each
      mutation causes local structural changes that compromise catalysis and/or
      thermostability. For example, the C153F mutation triggers conformational changes
      that block acetate product release channels, resulting in only 2% residual
      catalytic activity. In contrast, the H334R mutation causes structural changes in
      a polypeptide loop distant from the active site and results in 91% residual
      activity, but the thermostability of this mutant is significantly compromised.
      Strikingly, the catalytic activity of these mutants can be partially or fully
      rescued in vitro by the HDAC8 activator N-(phenylcarbamothioyl)benzamide. These
      results suggest that HDAC8 activators might be useful leads in the search for new
      therapeutic strategies in managing CdLS. 

PMID- 25075553
TI  - Substituent-enabled oxidative dehydrogenative cross-coupling of 1,4
      naphthoquinones with alkenes.
AB  - A Rh-catalyzed oxidative dehydrogenative cross-coupling of 1,4-naphthquinones
      with alkenes was achieved by using a substituent-enabled C(sp(2))-H
      functionalization (SEF) strategy. The method shows high functional group
      tolerance, broad substrate scope, and great potential for further functional
      transformations. 

PMID- 25075554
TI  - Direct laser writing of air-stable p-n junctions in graphene.
AB  - Photo-oxidation of spin-cast films of 6,13-bis(triisopropylsilylethynyl)
      pentacene has been exploited to develop a novel means of spatially modulating
      doping in graphene. The degree of n-doping of initially p-type graphene can be
      varied by laser irradiation time or intensity with carrier density change up to
      ~7 * 10(12) cm(-2). This n-doping approach is demonstrated as an effective means
      of creating p-n junctions in graphene. The ability to direct-write arbitrary
      shapes and patterns of n-doped regions in graphene simply by scanning a laser
      source should facilitate the exploitation of p-n junctions for a variety of
      electronic and optoelectronic device applications. 

PMID- 25075555
TI  - Th(As(III)4As(V)4O18): a mixed-valent oxoarsenic(III)/arsenic(V) actinide
      compound obtained under extreme conditions.
AB  - A high-temperature/high-pressure method was employed to investigate phase
      formation in the Th(NO3)4.5H2O-As2O3-CsNO3 system. It was observed that an excess
      of arsenic(III) in starting system leads to the formation of
      Th(As(III)4As(V)4O18), which is representative of a rare class of mixed-valent
      arsenic(III)/arsenic(V) compounds. This compound was studied with X-ray
      diffraction, energy-dispersive X-ray, and Raman spectroscopy methods.
      Crystallographic data show that Th(As(III)4As(V)4O18) is built from
      (As(III)4As(V)4O18)(4-) layers connected through Th atoms. The arsenic layers are
      found to be isoreticular to those in previously reported As2O3 and As3O5(OH), and
      the geometric differences between them are discussed. Bands in the Raman spectrum
      are assigned with respect to the presence of AsO3 and AsO4 groups. 

PMID- 25075556
TI  - Rapid detection, complete genome sequencing, and phylogenetic analysis of porcine
      deltacoronavirus.
AB  - In February 2014, porcine deltacoronavirus (PDCoV) was identified in the United
      States. We developed a PDCoV real-time reverse transcription PCR that identified
      PDCoV in 30% of samples tested. Four additional PDCoV genomes from the United
      States were sequenced; these had ~99%-100% nt similarity to the other US PDCoV
      strains. 

PMID- 25075557
TI  - Raman and infrared spectroscopy, DFT calculations, and vibrational assignment of
      the anticancer agent picoplatin: performance of long-range corrected/hybrid
      functionals for a platinum(II) complex.
AB  - Picoplatin, cis-[PtCl2(NH3)(2-picoline)], is a new promising anticancer agent
      undergoing clinical trials, which reveals high efficacy against many tumors and
      greatly reduced toxicity, in comparison to cisplatin. In this work, we present
      for the first time the Fourier-transform Raman and infrared spectra of
      picoplatin, in the region of 3500-50 cm(-1). The comprehensive theoretical
      studies on the molecular structure, the nature of Pt-ligand bonding, vibrational
      frequencies, and intensities were performed by employing different DFT methods,
      including hybrid (PBE0, mPW1PW, and B3LYP) and long-range-corrected hybrid
      density functionals (LC-omegaPBE, CAM-B3LYP). Various effective core potentials
      (ECP) and basis sets have been used. In the prediction of the molecular structure
      of picoplatin, the best results have been obtained by LC-omegaPBE, followed by
      PBE0, mPW1PW, and CAM-B3LYP density functionals, while the least accurate is
      B3LYP. The use of the LanL2TZ(f) ECP/basis set for Pt, in conjunction with all
      tested DFT methods, improves the calculated geometry of the title complex. The
      PBE0, mPW1PW, and CAM-B3LYP methods have shown the best performance in the
      calculations of the frequencies of Pt-ligand vibrations. A clear-cut assignment
      of all the bands in the IR and Raman spectra have been made on the basis of the
      calculated potential energy distribution (PED). The nature of the "vibrational
      signatures" of picoplatin have been determined. These results are indispensable
      for further investigation on drug-target interactions using vibrational
      spectroscopy. 

PMID- 25075559
TI  - Refertilization surgery. A surgeon's experience of over 27 years with nearly 2000
      patients.
AB  - AIM: The aim of this paper was to present the experiences of microsurgical
      refertilization in a single-centre study during a period of 27 years. METHODS:
      Nearly 2000 patients were operated by a single surgeon (JUS). A total of 1708
      patients were evaluated in a data base, 1164 were available for a follow-up. Both
      vasovasostomy (VV) and epididymovasostomy (EV) were carried out in a three-layer
      technique. Vasectomy reversal (VR) end-to-end VV was performed only if
      spermatozoa had been demonstrated at the epididymal stump of the vas. In all
      other cases of VR, EV was done in a preocclusive region of the epididymal tubule.
      In the cases of postinfectious obstruction (PIO) of seminal pathways, an EV was
      always carried out. RESULTS: The outpatient procedure of refertilization was
      associated with a very low complication rate, which underlines its minimal
      invasive character. The follow-up rate was 68%, the overall patency rate was 88%
      for VR and 67% for PIO and the pregnancy rate was 59% for VR and 38% for PIO.
      Secondary azoospermia was observed in 1% of the patients. CONCLUSION: In relation
      to the intervals of obstruction, the patency and pregnancy rates were higher
      after short-term obstruction than after long-term obstruction. There is a
      significant discrepancy between patency and pregnancy rates that is likely to be
      caused by a relevant number of patients with postoperative asthenozoospermia.

PMID- 25075558
TI  - Discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1) and mitogen
      activated protein kinase kinase kinase kinase 2 (MAP4K2).
AB  - We developed a pharmacophore model for type II inhibitors that was used to guide
      the construction of a library of kinase inhibitors. Kinome-wide selectivity
      profiling of the library resulted in the identification of a series of 4
      substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity
      against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2,
      as well as pharmacologically well interrogated kinases such as p38alpha (MAPK14)
      and ABL. Further investigation of the structure-activity relationship (SAR)
      resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as
      1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. Some of
      these inhibitors possess good pharmacokinetic properties that will enable their
      use in pharmacological studies in vivo. A 2.4 A cocrystal structure of TAK1 in
      complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out
      conformation characteristic of type II inhibitors. 

PMID- 25075560
TI  - A ten liter stacked microbial desalination cell packed with mixed ion-exchange
      resins for secondary effluent desalination.
AB  - The architecture and performance of microbial desalination cell (MDC) have been
      significantly improved in the past few years. However, the application of MDC is
      still limited in a scope of small-scale (milliliter) reactors and high-salinity
      water desalination. In this study, a large-scale (>10 L) stacked MDC packed with
      mixed ion-exchange resins was fabricated and operated in the batch mode with a
      salt concentration of 0.5 g/L NaCl, a typical level of domestic wastewater. With
      circulation flow rate of 80 mL/min, the stacked resin-packed MDC (SR-MDC)
      achieved a desalination efficiency of 95.8% and a final effluent concentration of
      0.02 g/L in 12 h, which is comparable with the effluent quality of reverse
      osmosis in terms of salinity. Moreover, the SR-MDC kept a stable desalination
      performance (>93%) when concentrate volume decreased from 2.4 to 0.1 L
      (diluate/concentrate volume ratio increased from 1:1 to 1:0.04), where only 0.875
      L of nonfresh water was consumed to desalinate 1 L of saline water. In addition,
      the SR-MDC achieved a considerable desalination rate (95.4 mg/h), suggesting a
      promising application for secondary effluent desalination through deriving
      biochemical electricity from wastewater. 

PMID- 25075561
TI  - Lab-in-a-shell: encapsulating metal clusters for size sieving catalysis.
AB  - Here we describe a lab-in-a-shell strategy for the preparation of multifunctional
      core-shell nanospheres consisting of a core of metal clusters and an outer
      microporous silica shell. Various metal clusters (e.g., Pd and Pt) were
      encapsulated and confined in the void space mediated by the entrapped polymer
      dots inside hollow silica nanospheres acting first as complexing agent for metal
      ions and additionally as encapsulator for clusters, limiting growth and
      suppressing the sintering. The Pd clusters encapsulated in hybrid core-shell
      structures exhibit exceptional size-selective catalysis in allylic oxidations of
      substrates with the same reactive site but different molecular size (cyclohexene
      ~0.5 nm, cholesteryl acetate ~1.91 nm). The solvent-free aerobic oxidation of
      diverse hydrocarbons and alcohols was further carried out to illustrate the
      benefits of such an architecture in catalysis. High activity, outstanding thermal
      stability and good recyclability were observed over the core-shell nanocatalyst. 

PMID- 25075562
TI  - ranibizumab in the management of advanced Coats disease Stages 3B and 4: long
      term outcomes.
AB  - BACKGROUND: Laser photocoagulation and cryotherapy to completely destroy
      telangiectatic vessels and ischemic retina in Coats disease is barely applicable
      in advanced cases with total retinal detachment, and globe survival is
      notoriously poor in Stages 3B and 4. Anti-vascular endothelial growth factor
      intravitreal injections may offer new prospects for these patients. METHODS: This
      study is a retrospective review of all consecutive patients with Coats disease
      treated with neoadjuvant or adjuvant intravitreal ranibizumab plus conventional
      and amblyopia treatment as appropriate. RESULTS: Nine patients (median age, 13
      months) presenting Coats Stages 3B and 4 (5 and 4 eyes, respectively) were
      included. Iris neovascularization resolved within 2 weeks and retinal
      reapplication within 4 months in all patients. At last follow-up, globe survival
      was 100% with anatomical success in 8 of the 9 eyes. With a median follow-up of
      50 months, fibrotic vitreoretinopathy was developed in 5 of the 9 cases, one
      leading to tractional retinal detachment and ultimately phthisis bulbi. The
      remaining 4 of the 9 eyes achieved some vision (range, 0.02-0.063). CONCLUSION:
      To the best of the authors' knowledge, this is the largest reported series of
      late-stage Coats undergoing anti-vascular endothelial growth factor therapy, a
      homogenous cohort of patients treated with a single agent and with the longest
      follow-up. This study supports the role of ranibizumab in advanced disease by
      transient restoration of the hemato-retinal barrier and suppression of
      neovascularization to facilitate classic treatment. At the last follow-up, the
      authors report unprecedented anatomical success and functional outcome.

PMID- 25075563
TI  - In vivo localization of antibodies raised against Eimeria maxima wall forming
      bodies during sexual intracellular development.
AB  - SUMMARY Apicomplexan parasites cause devastating diseases in humans and
      livestock. Previously we demonstrated that antibodies targeting transmissible
      forms of the apicomplexan parasite, Eimeria, are effective at reducing parasite
      shedding thus preventing the transmission of the disease. However, the mechanisms
      responsible have not been fully defined. Moreover, there is no direct evidence
      that the parasite-specific IgG antibodies can reach the parasite developing in
      the enterocytes of the infected chicken host. This study summarizes our efforts
      using host immunity, parasite proteomics and 3D microscopy to provide a step
      forward in our understanding of how this immune response works. Eimeria maxima is
      an important pathogen of poultry and used as a surrogate for a number of human
      pathogens including Toxoplasma and Plasmodium. Our studies demonstrate that
      immunization with the purified wall forming bodies (WFBs) results in a production
      of parasite-specific IgG antibodies, which have the ability to reach in situ
      gametocytes in the intestinal lumen and permeate the enterocyte/parasite
      membranes in order to bind to the cytoplasmic Type 1 and Type 2 WFBs. This raises
      the intriguing possibility that via this process antibodies block the development
      of Eimeria maxima in vivo. 

PMID- 25075564
TI  - Adoptive antitumor immunotherapy in vitro and in vivo using genetically activated
      erbB2-specific T cells.
AB  - The use of human T lymphocytes genetically modified to express chimeric antigen
      receptors on their surfaces has emerged as a promising treatment strategy for
      malignant tumors. We have transfected primary human peripheral T lymphocytes with
      a recombinant vector carrying DNA fragments encoding anti-erbB2
      scFv/Fc/CD28/CD3zeta chimeric antigen receptor using electroporation. Transfected
      T cells have been demonstrated to express anti-erB2 scFv/Fc on their surface and
      CD28/CD3zeta intracellularly. These modified T cells were able to specifically
      bind to erbB2 tumor-associated antigen on target tumor cells. After specific
      binding, modified T cells were activated to produce high levels of cytokines (not
      only interferon-gamma but also interluekin-2) and mediate lysis of erbB2-positive
      human tumor cells in an antigen-specific manner. Furthermore, such genetically
      modified human T cells significantly delayed the growth of subcutaneous erbB2
      positive human xenograft tumors after systemic administration. These preclinical
      studies suggest that human T cells can be modified genetically and redirected to
      tumors in cancer patients. 

PMID- 25075566
TI  - Analysis of the expression of interleukins, interferon beta, and nuclear factor
      kappa B in prostate cancer and their relationship with biochemical recurrence.
AB  - There are accumulating epidemiological, experimental, and genetic data supporting
      that prostate inflammation may contribute to prostate carcinogenesis, and several
      inflammatory-related molecules have been linked to tumorigenesis and prognosis in
      several tumors. The aim of this study was to evaluate tumor expression of
      inflammatory-related factors in prostate carcinomas and their possible
      relationship with biochemical recurrence (elevation of prostate-specific antigen
      serum levels). An immunohistochemical study was conducted using tissue
      microarrays and specific antibodies against interleukin-1beta (IL-1beta), IL-6,
      IL-10, IL-17, interferon beta (IFNbeta), and nuclear factor-kappa B (NF-kappaB).
      Determinations in cancer specimens from 118 patients with primary prostate cancer
      (78 without and 40 with recurrence during the follow-up period) were performed.
      Immunostaining for all the studied proteins was localized both in tumor cells and
      in stromal cells in the majority of tumors. High-score values for IL-1beta or low
      score values for IFNbeta were significantly associated with biochemical
      recurrence. The analysis defined a score value of 160 for IL-1beta and of 170 for
      IFNbeta as the optimal cutoff points that identified 32.7% and 73.2% of patients,
      respectively, having high probability of biochemical recurrence. Multivariate
      analysis according to a Cox model indicated that the cutoff point 170 for IFNbeta
      (P=0.035) was an independent factor associated with biochemical recurrence in
      patients with prostate cancer. Both IL-1beta and IFNbeta may be new biomarkers to
      distinguish high-risk/low-risk patients with prostate cancer, and to select
      appropriate therapeutic approaches. 

PMID- 25075565
TI  - Retrospective analysis of the safety and efficacy of high-dose interleukin-2
      after prior tyrosine kinase inhibitor therapy in patients with advanced renal
      cell carcinoma.
AB  - Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy
      for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the
      only agent that provides durable complete responses. The optimal sequence of
      these agents remains uncertain. This retrospective multi-institutional study
      examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB
      approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment
      characteristics among 40 consecutive patients with metastatic renal cell
      carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were
      retrospectively collected. The most common cardiac adverse events were grade 3
      hypotension and vascular leak syndrome. Six patients (15%) experienced other
      grade >=3 cardiac adverse events. There were 2 treatment-related deaths due to
      congestive heart failure, occurring in 1 patient with short TKI to HD-IL2
      interval and another patient with an abnormal baseline cardiac stress test. Best
      responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6,
      11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not
      evaluable patients. Median overall survival was 22 months. Administration of HD
      IL2 could be safe and effective after TKI therapy; however, careful selection of
      patients is critical. We recommend baseline cardiac risk factor assessment,
      screening with both cardiac stress test and echocardiogram, and allowing a TKI to
      HD-IL2 interval of at least 2 months. 

PMID- 25075567
TI  - Effectiveness and tolerability of ipilimumab: experiences from 198 patients
      included in a named-patient program in various daily-practice settings and
      multiple institutions.
AB  - BACKGROUND: Ipilimumab is an approved anti-cytotoxic T-lymphocyte-associated
      antigen-4 monoclonal antibody introducing immune responses in melanoma patients.
      Treatment experiences from named-patient programs support the evaluation of the
      efficacy and tolerability of new medicines under usual circumstances of health
      care practice. Here, the largest ever reported cohort treated with ipilimumab 3
      mg/kg alone is described. METHODS: This report retrospectively analyzes data of
      198 patients who were followed up in 15 hospital centers in Germany between April
      2010 and March 2013. Patients had received prior therapy for unresectable stage
      III or IV melanoma before receiving ipilimumab (4 doses of 3 mg/kg every 21 d).
      Routine staging and tumor response evaluation procedures were applied. RESULTS:
      Of the patients, 119 received the planned 4-course therapy schedule; in further
      79 patients, the number of doses was reduced mainly because of toxicity or fast
      progression. In all, 196 patients were eligible for evaluation of the efficacy of
      ipilimumab under routine care conditions. Median overall survival (OS) was 6.8
      months [95% confidence interval, 5.6-10.3] from the start of therapy. OS differed
      significantly among patients who received 4 doses (n=119) and those receiving <4
      doses (n=79) (14.2 vs. 2.0 mo; P<0.0001). The overall response rate (ORR) of 11%
      was in the same range as reported from previous clinical trials; and stable
      disease (SD) was observed in 11% resulting in a disease control rate (ORR+SD) of
      22%. In 23 of the 79 patients with reduced dosing, dose omission was most
      probably caused by toxicity, whereas 56 patients had progressive disease before
      receiving all 4 treatment cycles. Immune-related adverse events (irAE) were
      reported in 30% of all treated patients, the occurrence of irAE correlated
      significantly with the probability of response to therapy and prolonged OS.
      CONCLUSION: In this named-patient program including heavily pretreated patients,
      the efficacy and tolerability of ipilimumab 3 mg/kg corresponds with findings
      from the confirmatory clinical trial.

PMID- 25075568
TI  - [The impact of sleep endoscopy for obstructive sleep-disordered breathing in
      children and adolescents].
AB  - OBJECTIVE: Studies on the surgical treatment of OSAS in adults have shown an
      improved outcome after targeted therapy by drug-induced sleep endoscopy (DISE).
      So far, only a few studies have focused on this method in children. The aim of
      this study is to evaluate the impact of DISE for children with obstructive sleep
      disordered breathing and to determine the influence of DISE on treatment
      recommendations. SUBJECTS AND METHODS: The medical records of children (n=25) who
      underwent polysomnography and DISE between 05/2012 and 12/2013 were
      retrospectively reviewed. The subjects were divided into an UARS (upper airway
      resistance syndrome)/mild OSAS group (AHI<5; n=10) and a moderate/severe OSAS
      group (AHI>=5; n=15). RESULTS: The oropharynx was the most common site of
      obstruction. Prevalence of complete obstruction at the oropharynx was
      significantly higher in moderate or severe OSAS (p=0.02). The obstruction pattern
      of the velopharynx was significantly associated with the size of the adenoids
      (p=0.02), but tonsil and adenoid size were not related to the severity of OSAS.
      71% of children with grade IV tonsils showed complete obstruction of the
      oropharynx. After DISE, the initial management plan changed in 5 patients (20%).
      CONCLUSION: DISE is a promising technique to identify sites of obstruction in
      children with OSAS and to guide treatment decisions. Further studies are needed
      to predict persistent OSAS based on this tool.

PMID- 25075569
TI  - L-selenomethionine reduces platinum(IV) anticancer model compounds at strikingly
      faster rates than L-methionine.
AB  - L-Selenomethionine (SeMet), the predominant form of selenium acquired from the
      diet by humans, has been used as a supplement, and exhibit some important
      functions like cancer prevention and antioxidative defense. Its interactions with
      Pt(II) anticancer drugs have been characterized, but its redox reactions with
      platinum(IV) anticancer prodrugs have not been exploited. In this work, the
      oxidation of SeMet by Pt(IV) anticancer model compounds trans-[PtX2(CN)4](2-) (X
      = Cl, Br) was characterized. A stopped-flow spectrometer was used to record the
      rapid scan spectra and to follow the reaction kinetics over a wide pH range. An
      overall second-order rate law was derived: -d[Pt(IV)]/dt = k'[Pt(IV)][SeMet],
      where k' pertains to the observed second-order rate constants. The k'-pH profiles
      showed that k' increased only about 6 times even though the solution pH was
      varied from 0.25 to 10.5. The redox stoichiometry was determined as
      Delta[Pt(IV)]/Delta[SeMet] = 1 : (1.07 +/- 0.07), suggesting that SeMet was
      oxidized to selenomethionine selenoxide. The selenoxide together with its
      hydrated form was identified explicitly by high resolution mass spectral
      analysis. A reaction mechanism was proposed which encompassed three parallel rate
      determining steps relying on the protolytic species of SeMet. Rate constants of
      the rate-determining steps were obtained from the simulations of the k'-pH
      profiles. Activation parameters were determined for the reactions of the
      zwitterionic form of SeMet with the Pt(IV) complexes. A bridged electron transfer
      process is delineated in the rate-determining steps and several lines of evidence
      support the bridged electron transfer mode. Strikingly, reduction of
      [PtX2(CN)4](2-) by SeMet is 3.7 * 10(3)-5.7 * 10(4) times faster than that by L
      methionine. Some potential biological consequences resulting from the strikingly
      fast reduction are discussed.

PMID- 25075570
TI  - A portable microfluidic device for the rapid diagnosis of cancer metastatic
      potential which is programmable for temperature and CO2.
AB  - If metastasis of lung cancer can be found and treated early, a victim might have
      an improved chance to prevail over it, but routine examinations such as chest
      radiography, computed tomography and biopsy cannot characterize the metastatic
      potential of lung cancer cells; critical diagnoses to define optimal therapeutic
      strategies are thus lost. We designed a portable microfluidic device for the
      rapid diagnosis of cancer metastatic potential. Featuring a micro system to
      control temperature and a bicarbonate buffered environment, our device
      discriminates a rate of surface detachment as an index of the migratory ability
      of cells cultured on pH-responsive chitosan. We labeled metastatic subpopulations
      of lung cancer cell lines, and verified that our device is capable of separating
      cells according to their metastatic ability. As only few cells are needed, a
      patient's specimen from biopsies, e.g. from fine-needle aspiration, can be
      processed on site to offer immediate information to physicians. We expect that
      our design will provide valuable information in pre-operative evaluations to
      assist the definition of therapeutic plans for lung cancer, as well as for
      metastatic tumors of other types. 

PMID- 25075571
TI  - A dual arylboronic acid--aminothiourea catalytic system for the asymmetric
      intramolecular hetero-Michael reaction of alpha,beta-unsaturated carboxylic
      acids.
AB  - A bifunctional aminoboronic acid has been used to facilitate for the first time
      the intramolecular aza- and oxa-Michael reactions of alpha,beta-unsaturated
      carboxylic acids. The combination of an arylboronic acid with a chiral
      aminothiourea allowed for these reactions to proceed successfully in an
      enantioselective manner to afford the desired heterocycles in high yields and
      ee's (up to 96% ee). The overall utility of this dual catalytic system was
      demonstrated by a one-pot enantioselective synthesis of (+)-erythrococcamide B,
      which proceeded via sequential Michael and amidation reactions. 

PMID- 25075572
TI  - Prenatal management, pregnancy and pediatric outcomes in fetuses with septated
      cystic hygroma.
AB  - It has been reported that, compared with simple increased nuchal translucency,
      fetal cases with septated cystic hygroma (CH) are more likely to face perinatal
      handicaps. However, pediatric outcomes and proper prenatal counseling for this
      anomaly have not yet been truly defined. We performed this study to determine
      pregnancy and pediatric outcomes of fetuses with septated CH. We searched records
      for cases with septated CH and collected data for structural abnormalities,
      karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were
      also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH
      were enrolled in the study. Results showed that chromosomal abnormalities were
      present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome
      (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not
      found, had coexistent structural malformations; 25 (36.2%) cases had normal
      karyotype and morphology. The total number of live births and infants with
      unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively.
      Septated CH is associated with poor perinatal outcomes; therefore, karyotype
      analysis and ultrasonographic anomaly screening should be performed as initial
      steps, and expectant management should be offered to couples with euploid fetuses
      that have normal morphology. 

PMID- 25075573
TI  - Beneficial effects of Ginkgo biloba extract on insulin signaling cascade,
      dyslipidemia, and body adiposity of diet-induced obese rats.
AB  - Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the
      treatment of diabetes mellitus type 2. It remains unclear if its effects are due
      to an improvement of the insulin signaling cascade, especially in obese subjects.
      The aim of the present study was to evaluate the effect of GbE on insulin
      tolerance, food intake, body adiposity, lipid profile, fasting insulin, and
      muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine
      phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt
      phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet
      (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was
      divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats
      gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats
      were gavaged with the saline vehicle only. At the end of the treatment, the rats
      were anesthetized, insulin was injected into the portal vein, and after 90s, the
      gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt
      phosphorylation was performed using Western blotting. Serum levels of fasting
      insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL
      fractions were measured. An insulin tolerance test was also performed. Ingestion
      of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in
      a significant increase in body adiposity, plasma triacylglycerol, and glucose
      levels. In addition, GbE treatment significantly reduced food intake and body
      adiposity while it protected against hyperglycemia and dyslipidemia in diet
      induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V
      rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and
      reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that
      G. biloba might be efficient in preventing and treating obesity-induced insulin
      signaling impairment. 

PMID- 25075574
TI  - ERKs and mitochondria-related pathways are essential for glycyrrhizic acid
      mediated neuroprotection against glutamate-induced toxicity in differentiated
      PC12 cells.
AB  - The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA,
      a major compound separated from Glycyrrhiza Radix, which is a crude Chinese
      traditional drug) against glutamate-induced cytotoxicity in differentiated PC12
      (DPC12) cells. The results showed that GA treatment improved cell viability and
      ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12
      cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited
      glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced
      cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited
      phosphorylation of AKT (protein kinase B) and extracellular signal-regulated
      kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT.
      The presence of PD98059 (a mitogen-activated protein/extracellular signal
      regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3
      kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of
      glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria
      related pathways are essential for the neuroprotective effect of GA against
      glutamate-induced toxicity in DPC12 cells. The present study provides
      experimental evidence supporting GA as a potential therapeutic agent for use in
      the treatment of neurodegenerative diseases. 

PMID- 25075575
TI  - Putative role of ischemic postconditioning in a rat model of limb ischemia and
      reperfusion: involvement of hypoxia-inducible factor-1alpha expression.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is one of the most potent angiogenic
      growth factors. It improves angiogenesis and tissue perfusion in ischemic
      skeletal muscle. In the present study, we tested the hypothesis that ischemic
      postconditioning is effective for salvaging ischemic skeletal muscle resulting
      from limb ischemia-reperfusion injury, and that the mechanism involves expression
      of HIF-1alpha. Wistar rats were randomly divided into three groups (n=36 each):
      sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic
      postconditioning (group IPO). Each group was divided into subgroups (n=6)
      according to reperfusion time: immediate (0 h, T0), 1 h (T1), 3 h (T3), 6 h (T6),
      12 h (T12), and 24 h (T24). In the IPO group, three cycles of 30-s reperfusion
      and 30-s femoral aortic reocclusion were carried out before reperfusion. At all
      reperfusion times (T0-T24), serum creatine kinase (CK) and lactate dehydrogenase
      (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor
      alpha (TNF-alpha) concentrations, were measured in rats after they were killed.
      Histological and immunohistochemical methods were used to assess the skeletal
      muscle damage and HIF-1alpha expression in skeletal muscle ischemia. In groups IR
      and IPO, serum LDH and CK activities and TNF-alpha, IL-6, and IL-10
      concentrations were all significantly increased compared to group S, and HIF
      1alpha expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH
      and CK activities and TNF-alpha and IL-6 concentrations were significantly
      decreased, IL-10 concentration was increased, HlF-1alpha expression was down
      regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared
      to group IR. The present study suggests that ischemic postconditioning can reduce
      skeletal muscle damage caused by limb ischemia-reperfusion and that its
      mechanisms may be related to the involvement of HlF-1alpha in the limb ischemia
      reperfusion injury-triggered inflammatory response. 

PMID- 25075576
TI  - Association among genetic predisposition, gut microbiota, and host immune
      response in the etiopathogenesis of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and
      ulcerative colitis (UC), is a chronic disorder that affects thousands of people
      around the world. These diseases are characterized by exacerbated uncontrolled
      intestinal inflammation that leads to poor quality of life in affected patients.
      Although the exact cause of IBD still remains unknown, compelling evidence
      suggests that the interplay among immune deregulation, environmental factors, and
      genetic polymorphisms contributes to the multifactorial nature of the disease.
      Therefore, in this review we present classical and novel findings regarding IBD
      etiopathogenesis. Considering the genetic causes of the diseases, alterations in
      about 100 genes or allelic variants, most of them in components of the immune
      system, have been related to IBD susceptibility. Dysbiosis of the intestinal
      microbiota also plays a role in the initiation or perpetuation of gut
      inflammation, which develops under altered or impaired immune responses. In this
      context, unbalanced innate and especially adaptive immunity has been considered
      one of the major contributing factors to IBD development, with the involvement of
      the Th1, Th2, and Th17 effector population in addition to impaired regulatory
      responses in CD or UC. Finally, an understanding of the interplay among
      pathogenic triggers of IBD will improve knowledge about the immunological
      mechanisms of gut inflammation, thus providing novel tools for IBD control. 

PMID- 25075577
TI  - Prevalence and conditions associated with chronic pelvic pain in women from Sao
      Luis, Brazil.
AB  - The objective of the present study was to estimate the prevalence of chronic
      pelvic pain in the community of Sao Luis, capital of the State of Maranhao,
      Northeastern Brazil, and to identify independent conditions associated with it. A
      cross-sectional study was conducted, including a sample of 1470 women older than
      14 years predominantly served by the public health system. The interviews were
      held in the subject's home by trained interviewers not affiliated with the public
      health services of the municipality. The homes were visited at random according
      to the city map and the prevalence of the condition was estimated. To identify
      the associated conditions, the significant variables (P=0.10) were selected and
      entered in a multivariate analysis model. Data are reported as odds ratio and 95%
      confidence interval, with the level of significance set at 0.05. The prevalence
      of chronic pelvic pain was 19.0%. The independent conditions associated with this
      diagnosis were: dyspareunia (OR=3.94), premenopausal status (OR=2.95), depressive
      symptoms (OR=2.33), dysmenorrhea (OR=1.77), smoking (OR=1.72), irregular
      menstrual flow (OR=1.62), and irritative bladder symptoms (OR=1.90). The
      prevalence of chronic pelvic pain in Sao Luis is high and is associated with the
      conditions cited above. Guidelines based on prevention and/or early
      identification of risk factors may reduce the prevalence of chronic pelvic pain
      in Sao Luis, Brazil. 

PMID- 25075579
TI  - On the opto-electronic properties of phosphine and thiolate-protected undecagold
      nanoclusters.
AB  - We present here a detailed time-dependent density-functional theory investigation
      aimed at systematically dissecting the electronic spectra of two thiolate and
      phosphine protected undecagold nanoclusters. Calculations performed on the
      experimental structures of Au11(PPh3)7Cl3 and Au11(PPh3)7(SPyr)3 show that
      ligands have negligible contributions in the visible region. Metal -> ligand
      charge transfer transitions appear at energies well above the visible threshold,
      while transitions with some small ligand -> metal and ligand -> ligand character
      occur sporadically at even higher energies. Thus, the conjugation effect between
      the pi-electrons of the ligand and electrons of gold, recently hypothesized to
      interpret the spectra of phosphine and thiolate-protected nanoclusters, is not
      confirmed by the results of this study. 

PMID- 25075578
TI  - Effect of physical training on liver expression of activin A and follistatin in a
      nonalcoholic fatty liver disease model in rats.
AB  - Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in
      the liver and is associated with obesity and insulin resistance. Activin A is a
      member of the transforming growth factor beta (TGF)-beta superfamily and inhibits
      hepatocyte growth. Follistatin antagonizes the biological actions of activin.
      Exercise is an important therapeutic strategy to reduce the metabolic effects of
      obesity. We evaluated the pattern of activin A and follistatin liver expression
      in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF)
      diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF
      Swim) or a sedentary group (C-Sed and HF-Sed). Activin betaA subunit mRNA
      expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin
      mRNA expression was significantly lower in C-Swim and HF-Swim than in either C
      Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C
      rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to
      grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with
      the severity of steatosis ranging from grade 0 to grade 1. These data showed that
      exercise may reduce the deleterious effects of a high-fat diet on the liver,
      suggesting that the local expression of activin-follistatin may be involved. 

PMID- 25075580
TI  - Blast-induced lacerations - more examples of the diagnostic entity.

PMID- 25075581
TI  - Comparison of short-term outcomes in laparoscopic vs open hepatectomy.
AB  - IMPORTANCE: Despite the increasing role of laparoscopy in partial hepatic
      resection, its short-term benefit compared with traditional open surgery remains
      unclear. OBJECTIVE: To compare short-term (30-day) outcomes between laparoscopic
      (LH) and open (OH) partial hepatectomies. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective matched case-control study from April 1, 2004, to March 31, 2013,
      in a tertiary hepatobiliary referral center. Patients who underwent partial
      hepatic resection (OH or LH) for benign or malignant disease were matched first
      by extent of resection, then by pathological diagnosis, and finally by age and
      sex to the extent possible. EXPOSURE: Partial hepatectomy for liver disease. MAIN
      OUTCOMES AND MEASURES: Thirty-day morbidity and mortality rates. RESULTS: After
      the matching process, we included 104 patients (52 undergoing LH and 52
      undergoing OH) in the study. Patients were evenly matched with respect to age,
      sex, extent of resection, and diagnosis. Cirrhosis was present in 17 patients
      (33%) in each group. We found no difference in positive margin status (1 patient
      [2%] for LH vs 2 patients [4%] for OH; P > .99). Although the estimated blood
      loss differed significantly between groups (237 mL for LH vs 387 mL for OH; P =
      .049), we found no difference in the rate of perioperative blood transfusion (1
      patient [2%] for LH vs 5 [10%] for OH; P = .20). Operative time (219 minutes for
      LH vs 198 minutes for OH; P = .16), hospital length of stay (5 days for LH vs 6
      days for OH; P = .13), and readmission rate (4 patients [8%] for LH vs 5 [10%]
      for OH; P = .70) were similar in both groups. The rates of major complications (4
      patients [8%] for LH vs 4 patients [8%] for OH; P = 10), overall 30-day morbidity
      (22 patients [42%] for LH vs 19 [37%] for OH; P = .70), and 30-day mortality (1
      patient [2%] for LH vs 2 [4%] for OH; P > .99) were not significantly different.
      CONCLUSIONS AND RELEVANCE: Patients who undergo LH have similar short-term
      outcomes when compared with those who undergo OH. Laparoscopic hepatectomy was
      associated with lower intraoperative blood loss, although the clinical
      significance of this finding is uncertain given the lack of difference in
      perioperative transfusion or morbidity rates. In addition, we found no difference
      in margin status between the 2 groups. Future studies are needed to define which
      patients derive benefit from LH and to determine oncologic equivalence to OH.

PMID- 25075582
TI  - The many continua of psychosis.

PMID- 25075583
TI  - Natural history and surgical treatment of chordoma: a retrospective cohort study.
AB  - CONTEXT AND OBJECTIVE: Chordoma is a rare tumor with a high risk of locoregional
      recurrences. The aim of this study was analyze the long-term results from
      treating this pathological condition. DESIGN AND SETTING: Cohort study in a
      single hospital in Sao Paulo, Brazil. METHODS: This was a retrospective cohort
      study on 42 patients with chordoma who were treated at Hospital A. C. Camargo
      between 1980 and 2006. The hospital records were reviewed and a descriptive
      analysis was performed on the clinical-pathological variables. Survival curves
      were estimated using the Kaplan-Meier method and these were compared using the
      log-rank test. RESULTS: Nineteen patients were men and 23 were women. Twenty-five
      tumors (59.5%) were located in the sacrum, eleven (26.2%) in the skull base and
      six (14.3%) in the mobile spine. Surgery was performed on 28 patients (66.7%).
      The resection was considered to have negative margins in 14 cases and positive
      margins in 14 cases. The five-year overall survival (OS) was 45.4%. For surgical
      patients, the five-year OS was 64.3% (82.2% for negative margins and 51.9% for
      positive margins). In the inoperable group, OS was 37.7% at 24 months and 0% at
      five years. CONCLUSION: Complete resection is related to local control and
      definitively has a positive impact on long-term survival.

PMID- 25075584
TI  - Renal autotransplantation to treat renal artery aneurysm: case report.
AB  - CONTEXT: Renal artery aneurysm (RAA) is uncommon and usually asymptomatic, but
      complications like rupture or thromboembolism of the aneurysm can occur, with
      consequent renal infarction. Most of the clinical findings are found incidentally
      through imaging examinations, in investigating other diseases. Renal
      autotransplantation (RAT) is an alternative treatment for complex RAA, with
      satisfactory results described in the literature. CASE REPORT: The patient was a
      48-year-old man with a history of systemic arterial hypertension,
      thrombocytopenia and advanced hepatosplenic schistosomiasis. He complained of
      right lumbar pain, which was investigated through imaging examinations (computed
      tomography and angiotomography). These revealed right RAA of 2.5 cm in diameter.
      Evaluation by the vascular surgery team found that this was untreatable using
      endovascular methods. The treatment performed was open right nephrectomy with
      kidney preservation in solution, followed by aneurysmectomy, suturing of the
      injured artery and kidney reimplantation in the right iliac fossa with
      anastomosis of the iliac vessels and ureter. The durations of the surgery and
      kidney ischemia were 385 and 140 minutes, respectively. The patient was
      discharged on the 20th postoperative day, with creatinine concentration of 1.4
      mg/dL, urea 41 mg/dL, urine volume 1400 mL/24 h and ascites treated with
      diuretics. CONCLUSION: RAT is indicated basically in three situations:
      extracorporeal reconstruction of complex aneurysms of the renal pedicle,
      extensive ureteral injury, and conservative kidney cancer surgery in patients
      with a single kidney. This study presents a case of a patient with advanced liver
      disease and RAA that was untreatable using endovascular methods and was
      successfully treated using RAT.

PMID- 25075585
TI  - Comorbidity between Klinefelter syndrome and diaphragmatic hernia. A case report.
AB  - CONTEXT: Intrathoracic cystic lesions have been diagnosed in a wide variety of
      age groups, and the increasing use of prenatal imaging studies has allowed
      detection of these defects even in utero. CASE REPORT: A 17-year-old pregnant
      woman in her second gestation, at 23 weeks of pregnancy, presented an ultrasound
      with evidence of a cystic anechoic image in the fet al left hemithorax. A
      morphological ultrasound examination performed at the hospital found that this
      cystic image measured 3.7 cm x 2.1 cm x 1.6 cm. Polyhydramnios was also present.
      At this time, the hypothesis of cystic adenomatoid malformation was raised. Fet
      al echocardiography showed only a dextroposed heart. Fet al magnetic resonance
      imaging produced an image compatible with a left diaphragmatic hernia containing
      the stomach and at least the first and second portions of the duodenum, left lobe
      of the liver, spleen, small intestine segments and portions of the colon. The
      stomach was greatly distended and the heart was shifted to the right. There was
      severe volume reduction of the left lung. Fet al karyotyping showed the
      chromosomal constitution of 47,XXY, compatible with Klinefelter syndrome. In our
      review of the literature, we found only one case of association between
      Klinefelter syndrome and diaphragmatic hernia. CONCLUSIONS: We believe that the
      association observed in this case was merely coincidental, since both conditions
      are relatively common. The chance of both events occurring simultaneously is
      estimated to be 1 in 1.5 million births.

PMID- 25075586
TI  - Leadership, management and teamwork learning through an extra-curricular project
      for medical students: descriptive study.
AB  - CONTEXT AND OBJECTIVE: Professionalism in medicine requires preparation for the
      globalized world. Our objective was to describe a project that introduces medical
      students to the community, hospital and laboratory activities, thereby allowing
      them to gain experience in people management, leadership and teamwork. DESIGN AND
      SETTING: Descriptive study of the process applied at a philanthropic medical
      school in Curitiba, Parana. METHOD: Inclusion of management and leadership
      practices as part of the medical degree program. RESULTS: The study groups
      consisted of fifteen students. After six months, any of the participants could be
      elected as a subcoordinator, with responsibility for managing tasks and
      representing the team in hospital departments and the community. The activities
      required increasing levels of responsibility. In medical schools, students'
      involvement in practical activities is often limited to observation. They are not
      required to take responsibilities or to interact with other students and
      stakeholders. However, they will become accountable, which thus has an adverse
      effect on all involved. The learning space described here aims to fill this gap
      by bringing students closer to the daily lives and experiences of healthcare
      professionals. CONCLUSION: Being a physician requires not only management and
      leadership, but also transferrable competencies, communication and critical
      thinking. These attributes can be acquired through experience of teamwork, under
      qualified supervision from teaching staff. Students are thus expected to develop
      skills to deal with and resolve conflicts, learn to share leadership, prepare
      others to help and replace them, adopt an approach based on mutual responsibility
      and discuss their performance.

PMID- 25075587
TI  - Near-infrared photocatalytic activity induced by intrinsic defects in Bi2MO6 (M =
      W, Mo).
AB  - The electronic structure and related photocatalytic properties of Bi2MO6 (M = W,
      Mo) with various intrinsic defects are studied based on the first-principles
      density functional theory (DFT). Our results indicate that O vacancies form
      easily in both Bi2WO6 and Bi2MoO6 under Bi rich/O poor conditions. The near
      infrared light transitions can be realized involving electrons from the O vacancy
      induced impurity states within the band gap to the conduction band. Rather than
      acting as photogenerated carrier recombination centers, the impurity states
      caused by O vacancies favor the transfer of photogenerated holes and further
      benefit the photocatalytic process due to the delocalized nature. The spatial
      separation of photogenerated carriers among different layers can be realized,
      which reduces the carrier recombination and improves the photocatalytic activity.
      In addition, Bi2WO6 with O vacancies is desirable for having better near-infrared
      photocatalytic performance than Bi2MoO6 due to the larger mobility of
      photogenerated holes. 

PMID- 25075588
TI  - Response to Maniatis critique of anchoring theory.

PMID- 25075589
TI  - Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus open
      surgery for great saphenous vein varices.
AB  - BACKGROUND: Minimally invasive techniques to treat great saphenous varicose veins
      include ultrasound-guided foam sclerotherapy (UGFS), radiofrequency ablation
      (RFA) and endovenous laser therapy (EVLT). Compared with flush saphenofemoral
      ligation with stripping, also referred to as open surgery or high ligation and
      stripping (HL/S), proposed benefits include fewer complications, quicker return
      to work, improved quality of life (QoL) scores, reduced need for general
      anaesthesia and equivalent recurrence rates. This is an update of a review first
      published in 2011. OBJECTIVES: To determine whether endovenous ablation
      (radiofrequency and laser) and foam sclerotherapy have any advantages or
      disadvantages in comparison with open surgical saphenofemoral ligation and
      stripping of great saphenous vein varices. SEARCH METHODS: For this update the
      Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched
      the Specialised Register (last searched January 2014) and CENTRAL (2013, Issue
      12). Clinical trials databases were also searched for details of ongoing or
      unpublished studies. SELECTION CRITERIA: All randomised controlled trials (RCTs)
      of UGFS, EVLT, RFA and HL/S were considered for inclusion. Primary outcomes were
      recurrent varicosities, recanalisation, neovascularisation, technical procedure
      failure, patient QoL scores and associated complications. DATA COLLECTION AND
      ANALYSIS: CN and RB independently reviewed, assessed and selected trials which
      met the inclusion criteria. CN and RB extracted data and used the Cochrane
      Collaboration's tool for assessing risk of bias. CN and RB contacted trial
      authors to clarify details as needed. MAIN RESULTS: For this update, eight
      additional studies were included making a total of 13 included studies with a
      combined total of 3081 randomised patients. Three studies compared UGFS with
      surgery, eight compared EVLT with surgery and five compared RFA with surgery (two
      studies had two or more comparisons with surgery). Study quality, evaluated
      through the six domains of risk of bias, was generally moderate for all included
      studies, however no study blinded participants, researchers and clinicians or
      outcome assessors. Also, nearly all included studies had other sources of bias.
      The overall quality of the evidence was moderate due to the variations in the
      reporting of results, which limited meaningful meta-analyses for the majority of
      proposed outcome measures. For the comparison UGFS versus surgery, the findings
      may have indicated no difference in the rate of recurrences in the surgical group
      when measured by clinicians, and no difference between the groups for symptomatic
      recurrence (odds ratio (OR) 1.74, 95% confidence interval (CI) 0.97 to 3.12; P =
      0.06 and OR 1.28, 95% CI 0.66 to 2.49, respectively). Recanalisation and
      neovascularisation were only evaluated in a single study. Recanalisation at < 4
      months had an OR of 0.66 (95% CI 0.20 to 2.12), recanalisation > 4 months an OR
      of 5.05 (95% CI 1.67 to 15.28) and for neovascularisation an OR of 0.05 (95% CI
      0.00 to 0.94). There was no difference in the rate of technical failure between
      the two groups (OR 0.44, 95% CI 0.12 to 1.57). For EVLT versus surgery, there
      were no differences between the treatment groups for either clinician noted or
      symptomatic recurrence (OR 0.72, 95% CI 0.43 to 1.22; P = 0.22 and OR 0.87, 95%
      CI 0.47 to 1.62; P = 0.67, respectively). Both early and late recanalisation were
      no different between the two treatment groups (OR 1.05, 95% CI 0.09 to 12.77; P =
      0.97 and OR 4.14, 95% CI 0.76 to 22.65; P = 0.10). Neovascularisation and
      technical failure were both statistically reduced in the laser treatment group
      (OR 0.05, 95% CI 0.01 to 0.22; P < 0.0001 and OR 0.29, 95% CI 0.14 to 0.60; P =
      0.0009, respectively). Long-term (five-year) outcomes were evaluated in one study
      so no association could be derived,but it appeared that EVLT and surgery
      maintained similar findings. Comparing RFA versus surgery, there were no
      differences in clinician noted recurrence (OR 0.82, 95% CI 0.49 to 1.39; P =
      0.47); symptomatic noted recurrence was only evaluated in a single study. There
      were also no differences between the treatment groups for recanalisation (early
      or late) (OR 0.68, 95% CI 0.01 to 81.18; P = 0.87 and OR 1.09, 95% CI 0.39 to
      3.04; P = 0.87, respectively), neovascularisation (OR 0.31, 95% CI 0.06 to 1.65;
      P = 0.17) or technical failure (OR 0.82, 95% CI 0.07 to 10.10; P = 0.88).QoL
      scores, operative complications and pain were not amenable to meta-analysis,
      however quality of life generally increased similarly in all treatment groups and
      complications were generally low, especially major complications. Pain reporting
      varied greatly between the studies but in general pain was similar between the
      treatment groups. AUTHORS' CONCLUSIONS: Currently available clinical trial
      evidence suggests that UGFS, EVLT and RFA are at least as effective as surgery in
      the treatment of great saphenous varicose veins. Due to large incompatibilities
      between trials and different time point measurements for outcomes, the evidence
      is lacking in robustness. Further randomised trials are needed, which should aim
      to report and analyse results in a congruent manner to facilitate future meta
      analysis.

PMID- 25075590
TI  - Laryngeal narrowing during nasal ventilation does not originate from
      bronchopulmonary C-fibers.
AB  - We previously showed that nasal pressure support ventilation (nPSV) can lead to
      active inspiratory laryngeal narrowing, which originates from the stimulation of
      bronchopulmonary receptors. Among the three major types of bronchopulmonary
      receptors, which are variably stimulated by lung distension, C-fiber endings are
      remarkable, given that their stimulation can also trigger laryngeal closure.
      Taking advantage of our lamb model with blocked C-fibers, we aimed to assess
      whether bronchopulmonary C-fiber endings are involved in the active inspiratory
      laryngeal narrowing during nPSV. Nine lambs were surgically instrumented to
      assess states of alertness, electrical activity of a glottal constrictor (EaTA),
      respiratory movements and arterial blood gases. Forty-eight hours later, two
      polysomnographic recordings were performed during nPSV 15/4 cmH2O, before and
      after C-fiber blockade. During nPSV, blockade of C-fibers did not prevent
      inspiratory EaTA (present for 74+/-41% of respiratory cycles vs. 64+/-35%,
      p=0.9). We conclude that active inspiratory laryngeal narrowing during nPSV does
      not originate from bronchopulmonary C-fiber endings.

PMID- 25075591
TI  - Association between sensitisation and pain-related behaviours in an experimental
      canine model of osteoarthritis.
AB  - Evaluation of nociceptive sensitisation in canine osteoarthritis studies has been
      poorly reported, or even related to other clinical symptoms. In 16 dogs, peak
      vertical force (PVF), subjective pain assessment using 3 scales, sympathetic
      stress response with electrodermal activity (EDA) measurement, and behavioural
      changes with video analysis and telemetered motor activity were quantified at
      baseline (D-7), and 28 and 56 days post transection of the cranial cruciate
      ligament. As markers of central sensitisation, selected spinal cord biomarkers
      (substance P and transthyretin) were quantified at D56. Electrical withdrawal
      thresholds on the stifle and the tail were measured as indicative of peripheral
      and central quantitative sensory testing (QST) sensitisation, respectively. The
      effects of vehicle administration (n=8) were compared with tiludronate (2mg/kg
      subcutaneously, q2 week, starting at D0) administration. Generalized estimated
      equations tested the association between the behavioural and physiological
      methods and QST sensitisation, and therefore the sensitivity of the methods for
      detecting treatment efficacy. Compared to tiludronate, at D56, vehicle-treated
      dogs had increased spinal substance P (P=0.01), concomitant decreased
      transthyretin (P=0.02), and (compared to baseline) demonstrated peripheral and
      central QST sensitisation, which was not present for tiludronate. Only PVF, the
      spontaneous behaviour "walking with full weight-bearing," and EDA were associated
      with occurrence of QST sensitisation and indicated significant tiludronate
      analgesic efficacy after inclusion of central QST sensitisation as a predictor
      variable in the statistical model. This study establishes the strong interest to
      implement QST as a predictor of canine osteoarthritis pain symptoms explained by
      pain sensitisation.

PMID- 25075592
TI  - ECG of the Month. Unexpected Atrioventricular Conduction in High-Grade
      Atrioventricular Block. DIAGNOSIS: Sinus rhythm; high-grade second-degree
      atrioventricular block with a junctional escape rhythm and three capture
      complexes, each with right bundle branch block aberration; possible septal
      myocardial infarct of indeterminate age; ST-T and U wave changes suggesting
      hypokalemia.
AB  - A 90-year-old man with a history of high blood pressure, a cerebrovascular
      accident without focal residua, dementia, and stage 3 chronic kidney disease went
      to the emergency department because of dizziness and near syncope. His
      medications were aspirin 81 mg qd, clopidogrel 75 mg qod, escitalopram oxalate 10
      mg qd, quetiapine fumarate 25 mg qd, and memantine hydrochloride 10 mg qd. He had
      orthrostatic hypotension with supine blood pressure of 173/77 mmHg falling to
      116/68 on standing, while pulse increased from 66 to 84 beats/min. He received IV
      fluid and returned home. Two days later, he saw his primary care physician
      because of episodes of dizziness and confusion. The Figure shows an
      electrocardiogram recorded during that visit. 

PMID- 25075593
TI  - Elbow synovium as the initial site of colon adenocarcinoma metastasis: diagnosis
      by arthroscopic biopsy.
AB  - An acutely painful and swollen isolated joint has a broad differential. We
      present the case of an elderly male with four-month progressive, painful swelling
      of the right elbow. After an initial workup for inflammatory arthropathies was
      nondiagnostic and a trial of conservative management failed to relieve his pain,
      a diagnostic arthroscopy was performed. Biopsy revealed metastatic colon
      adenocarcinoma isolated to the synovial tissue of the elbow. This case provides
      an example of the presentation and progression of synovial metastasis from a
      visceral cancer and can potentially guide physicians in the diagnosis and
      management of similar cases. 

PMID- 25075594
TI  - Celiacomesenteric trunk: a rare anatomical variation with potential clinical and
      surgical implications.
AB  - The arterial supply of the abdominal viscera is derived via three single
      arteries: the celiac axis, the superior mesenteric artery, and the inferior
      mesenteric artery. These arteries usually originate separately from the ventral
      aspect of the abdominal aorta. In some cases, two or more of these arteries may
      originate from a common trunk. The celiacomesenteric trunk is a rare condition
      that can generate clinical and surgical complications. Preoperative knowledge of
      vascular anomalies is critical when planning a surgical approach. We report a
      patient who underwent Multi-detector Computed Tomography (MDCT) before a vascular
      procedure, and a common trunk for celiac axis and superior mesenteric artery
      (celiac mesenteric trunk) was incidentally found. 

PMID- 25075595
TI  - Radiological evolution of relapsing polychondritis.
AB  - Relapsing Polychondritis (RP) is a systemic condition characterized by chronic,
      episodic inflammation, especially of cartilaginous and proteoglycan-rich
      structures. The etiology of this rare autoimmune disease is unknown, and so far,
      there is very little data available for non-Caucasians. RP presents with a
      constellation of non-specific inflammation, which sometimes appear in
      characteristic locations. Radiology is important in supporting the diagnosis, and
      this paper presents a case of a non-Caucasian patient monitored radiologically
      from early onset to the terminal stages. 

PMID- 25075597
TI  - Plasmacytoma presenting as missing rib on chest film: a case report and review of
      the literature.
AB  - A 33-year-old man presented to the emergency department (ED) with chief complaint
      of chest pain, persisting for approximately one year. Chest X-ray revealed he was
      missing the right posterior fifth rib. Physical examination showed no surgical
      scars, and he reported no history of chest trauma. A CT of his chest demonstrated
      a mass involving the posterior aspect of the right fifth rib, and subsequent
      biopsy revealed plasma cells. Laboratory results indicated the tumor was a
      solitary plasmacytoma of the rib. He was referred to oncology and treated with
      radiation therapy. This case report illustrates an unusual presentation of a
      solitary plasmacytoma of the rib. 

PMID- 25075596
TI  - Bilateral ultrasound-guided supraclavicular block in a patient with severe
      electrocution injuries of the upper extremities.
AB  - The performance of bilateral supraclavicular brachial plexus nerve blocks is
      controversial. We present the challenging case of a 29-year-old male who suffered
      bilateral high-voltage electrocution injuries to the upper extremities, resulting
      in severe tissue damage, sensory and motor deficits, and wounds in both axillae.
      This injury necessitated bilateral below-elbow amputations. His postoperative
      course was complicated by pain refractory to intravenous narcotics. The decision
      was made to attempt bilateral supraclavicular brachial plexus blocks. Our
      concerns with this approach included the risks of pneumothorax and respiratory
      failure due to phrenic nerve block. Initial attempts at brachial plexus blockade
      using nerve stimulation were unsuccessful; therefore, ultrasound guidance was
      employed. With vigilant monitoring in an intensive care unit setting, we were
      able to safely perform bilateral continuous supraclavicular brachial plexus nerve
      blocks with an excellent analgesic response and no noted complications. 

PMID- 25075598
TI  - Mucinous cystic neoplasm of pancreas in a male patient: a case report and review
      of the literature.
AB  - Mucinous cystic neoplasms (MCNs) are among the most common primary cystic
      neoplasms of pancreas. These lesions usually occur in body and tail of the
      pancreas and are characterized by the presence of ovarian type stroma in the
      pathological evaluation. Mucinous cystic neoplasms have significant malignant
      potential; therefore, their diagnosis and resection is of utmost importance.
      Mucinous cystic neoplasms typically occur in women. Only a few cases have been
      previously reported in male patients. In this case report, we present a 48-year
      old man who was referred to our center due to an incidentally found cystic lesion
      in the tail of the pancreas that was increasing in size in serial evaluation. The
      patient underwent open distal pancreatectomy. The pathology showed mucinous
      cystic neoplasm with characteristic ovarian type stroma and positive staining for
      estrogen and progesterone receptors. This case report shows that mucinous cystic
      neoplasms can occur in men and should be considered in differential diagnosis of
      cystic pancreatic lesions in this population. 

PMID- 25075599
TI  - Sphenoid sinus dehiscence as a risk for visual consequences in an
      immunocompromised patient.
AB  - Isolated sphenoid sinus disease is a rare entity with severe and potentially life
      threatening sequela. Because of the proximity of the sinus to the orbit,
      anatomical defects within the surrounding bony structures can facilitate
      communication with orbital content, predisposing the patient to substantial
      visual consequences. We report a case of a 51-year-old immunocompromised male who
      presented with headache and gradual unilateral decreases in vision. Computed
      tomography revealed opacification of the left sphenoid sinus accompanied by
      unusual bony dehiscence of the proximal optic canal. Early recognition and
      treatment of sphenoid sinusitis requires urgent surgical intervention with delay
      of treatment potentially leading to irreversible blindness or other devastating
      consequences. Bony dehiscence of the sphenoid sinus overlying the optic nerve has
      only been found in 4% of cadavers. It is associated with increased risk of
      orbital complications and predicts a poor prognosis. Immediate intervention is
      particularly important in immunocompromised individuals who are at greater risk
      of these severe complications. 

PMID- 25075600
TI  - Protecting the Private Practice of Medicine. Direct primary care: kicking
      insurance out of the exam room.

PMID- 25075601
TI  - Radiology case of the month. 49-year-old female with an anterior mediastinal
      mass.
AB  - Castleman's disease is an uncommon benign lymphoproliferative disorder
      characterized by hypervascular lymphoid hyperplasia. Two distinct histologic
      variants of Castleman's disease exist - hyaline vascular type and plasma cell
      type. The etiology is uncertain; however, it is thought to be inflammatory or
      hamartomatous in nature. Castleman's disease can occur at any age with a peak
      incidence in the third to fourth decade. This article presents a case of
      Castleman's disease in a female patient and aims to educate about the natural
      history, diagnosis, and management of the disease. 

PMID- 25075603
TI  - Pathology case of the month: sudden unexplained death in a young adult with known
      alcohol abuse.
AB  - A 35-year-old, recently deceased woman with a medical history known only to
      include Hepatitis C and alcohol abuse was transferred to the autopsy service for
      an unrestricted autopsy under coroner authorization following a sudden
      unexplained death. External examination revealed marked scleral icterus and
      cutaneous jaundice. Internal examination was remarkable for 3 liters of ascitic
      fluid and established cirrhosis with a micronodular pattern (nodules all <0.3 cm
      in diameter). Numerous, small, firm vegetations were identified along the edges
      of the tricuspid, mitral, and aortic valves. There was no obvious necrosis or
      tissue destruction seen grossly. Zones of prominent myocardial discoloration and
      hemorrhage were seen in all regions (anterior, lateral, and posterior) of the
      left ventricular myocardium, as well as within the interventricular septal
      myocardium. Multiple punctate lesions, up to 2 cm in diameter with a greenish hue
      and associated with tissue necrosis were seen overlying the cerebral cortex, as
      well as within the intracerebral parenchyma. Tissues were fixed in formalin for
      subsequent microscopic examination, and representative images from the aortic
      valve, and from the cerebral cortex, are seen below.

PMID- 25075604
TI  - Anti-MDA5 antibody-positive dermatomyositis with lethal progressive interstitial
      lung disease and advanced gastric cancer.

PMID- 25075605
TI  - Growing pigs' drinking behaviour: number of visits, duration, water intake and
      diurnal variation.
AB  - Individual drinking patterns are a potential tool for disease monitoring in pigs.
      However, to date, individual pig drinking behaviour has not been described, and
      effects of external factors have not been examined. The aim of this study was to
      perform detailed quantification of drinking behaviour of growing pigs and to
      examine effects of period of day and effects of competition for access to the
      drinking nipple on the drinking behaviour, amount of water used and water
      wastage. In all, 52 cross-bred castrated male pigs (live weight 20.5+/-1.7 kg;
      mean+/-s.d.) maintained as either 3 (N3) or 10 (N10) pigs per pen and water
      nipple (four groups/treatment) were used. All pigs were fitted with a transponder
      ear tag. A radio frequency identification reader recorded and time stamped visits
      at the nipple. In each pen, water flow was logged every second. The drinking
      behaviour was recorded for 4 consecutive days and analysed using a linear mixed
      model. Overall, the pigs spent 594 s at the nipple during 24 h distributed among
      44 visits. During this period, 5 l of water were used, of which >30% was wasted.
      Social competition did not affect the drinking behaviour over 24 h, except for
      the proportion of interrupted visits where pigs, kept with recommended nipple
      availability (N10), showed an increased proportion of interrupted drinking bouts
      compared with pigs kept at very low level of competition (N3) (0.18+/-0.01 v.
      0.11+/-0.01; P<0.01). However, splitting data into 8-h periods (P1, P2, P3)
      starting from 0600 h revealed differences between treatments, showing that in N3,
      water use per visit was lower in P1 than P2 and P3 (110+/-10 v. 126+/-7 and 132+/
      7 ml; P<0.05), whereas in N10, the water used per visit was higher during P3 than
      during the other periods (P1: 107+/-14 ml, P2: 112+/-10 ml v. P3: 151+/-10 ml;
      P<0.001). A similar pattern was found for visit duration. In N3, fewer nipple
      visits were observed in P2 than P1 (15.6+/-1.2 v. 22.0+/-1.2; P<0.001), whereas
      no difference was found between P1 and P2 in N10. The results demonstrate that
      growing pigs at the two levels of competition maintained a comparable level of 24
      h water intake by changing behavioural variables involved in drinking. This
      dynamic characteristic of drinking behaviour means that if individual drinking
      patterns are to be used as disease monitoring tools, it is important to consider
      effects of external factors and include data on period level to allow rapid
      detection of behavioural changes. 

PMID- 25075606
TI  - Food security status among grade 5 students in Nova Scotia, Canada and its
      association with health outcomes.
AB  - OBJECTIVE: Food security (FS) exists when all people, at all times, have physical
      and economic access to sufficient, safe and nutritious food to meet their needs.
      The present research sought to determine whether students from households
      experiencing moderate or severe food insecurity (FI) had poorer diet quality,
      higher body weights and poorer psychosocial outcomes than students from
      households classed as having high FS or marginal FI status. DESIGN: Population
      based survey conducted in schools. Multiple regression analysis was used to
      explore associations between FS status (high FS; marginal, moderate, severe FI),
      dietary behaviours and intake, and health-related outcomes (body weight, quality
      of life, mood, peer relationships, externalizing problems). SETTING: Nova Scotia,
      Canada. SUBJECTS: Grade 5 students (n 5853), aged 10-11 years, with complete
      information on FS status and student outcomes. RESULTS: In this sample, rates of
      household FS were 73.5% (high FS), 8.3% (marginal FI) 10.2% (moderate FI) and
      7.1% (severe FI status). Students living in households experiencing moderate or
      severe FI had poorer diet quality, higher BMI and poorer psychosocial outcomes
      than students classed as having high FS or marginal FI. CONCLUSIONS: These
      findings provide important evidence for policy makers on the prevalence of FI
      among families in Nova Scotia with grade 5 children and its relationship with
      childhood nutrition, psychosocial and quality of life factors, and weight status.

PMID- 25075607
TI  - Shared reality of the abusive and the vulnerable: the experience of aging for
      parents living with abusive adult children coping with mental disorder.
AB  - BACKGROUND: Increasing numbers of aging parents are finding themselves in the
      role of caregiver for their mentally ill adult child due to global
      deinstitutionalization policy. The aim of this paper is to describe the daily
      aging experience of parents abused by an adult child with mental disorder and the
      challenges confronting them in this shared reality. METHODS: Data collection was
      performed through in-depth semi-structured interviews with 16 parents, followed
      by content analysis. RESULTS: Three major themes emerged: (a) old age as a
      platform for parent's vulnerability facing ongoing abuse; (b) "whose needs come
      first?" in a shared reality of abusive and vulnerable protagonists; (c) changes
      in relationship dynamics. CONCLUSIONS: Old age becomes an arena for redefined
      relationships combining increased vulnerability, needs of both sides, and its
      impact on the well-being of the aging parents. This calls for better insights and
      deeper understanding in regard to intervention with such families.

PMID- 25075608
TI  - Phenolic Compounds of Cereals and Their Antioxidant Capacity.
AB  - Phenolic compounds play an important role in health benefits because of their
      highly antioxidant capacity. In this review, total phenolic contents (TPCs),
      phenolic acid profile and antioxidant capacity of the extracted from wheat, corn,
      rice, barley, sorghum, rye, oat, and millet, which have been recently reported,
      are summarized. The review shows clearly that cereals contain a number of
      phytochemicals including phenolics, flavonoids, anthocyanins, etc. The
      phytochemicals of cereals significantly exhibit antioxidant activity as measured
      by trolox equivalent antioxidant capacity (TEAC), 2,2-diphenyl-1-picrylhydrazyl
      radical scavenging, reducing power, oxygen radical absorbance capacity (ORAC),
      inhibition of oxidation of human low-density lipoprotein (LDL) cholesterol and
      DNA, Rancimat, inhibition of photochemilumenescence (PCL), and iron(II) chelation
      activity. Thus, the consumption of whole grains is considered to have
      significantly health benefits in prevention from chronic diseases such as
      cardiovascular disease, diabetes, and cancer because of the contribution of
      phenolic compounds existed. In addition, the extracts from cereal brans are
      considered to be used as a source of natural antioxidants.

PMID- 25075610
TI  - Characteristics of prescription and nonprescription sleep medication users in the
      United States.
AB  - Sleep deprivation and disturbances can result in lowered productivity and
      increased errors/accidents. Little is known about population characteristics
      associated with the use of sleep medications. The objective of this study was to
      investigate the association of sociodemographic factors with the use of sleep
      medications in the US population. This was a retrospective, cross-sectional study
      using data from the 2010 Medical Expenditure Panel Survey, which contains
      nationally representative data from the US population. The study population
      included all respondents older than 18 years of age. A multiple logistic
      regression model was built to analyze the odds of reporting use of prescription
      or nonprescription sleep medication. In 2010, an estimated 19 million survey
      respondents (10%) used some type of medication to fall asleep. The odds of
      reporting use of sleep medication were significantly lower among males (odds
      ratio [OR]=0.695, 95% confidence interval [CI]=0.599-0.808), and the uninsured
      (OR=0.613, 95% CI=0.439-0.855). The odds of sleep medication use were
      significantly higher among age groups 24-44 years and 44-64 years as compared
      with 18-24 years (OR=1.868, 95% CI=1.254-2.781 and OR=1.936, 95% CI=1.309-2.865,
      respectively), whites (OR=2.003, 95% CI=1.597-2.512) compared with African
      Americans, or non-Hispanics (OR=1.609, 95% CI=1.316-1.967), the unemployed
      (OR=1.773, 95% CI=1.496-2.101), and respondents with depression (OR=2.077, 95%
      CI=1.463-2.951) or anxiety (OR=6.855, 95% CI=4.998-9.403). Differences in sleep
      medication use were seen among specific subpopulations. Further research into why
      such differences exist is necessary. The factors identified in this study should
      be investigated further to identify vulnerable populations to determine the
      underlying causes of sleep disorders.

PMID- 25075609
TI  - Autism and sensory processing disorders: shared white matter disruption in
      sensory pathways but divergent connectivity in social-emotional pathways.
AB  - Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical
      sensory behaviors. In fact, hyper- or hyporeactivity to sensory input or unusual
      interest in sensory aspects of the environment is now included in the DSM-5
      diagnostic criteria. However, there are children with sensory processing
      differences who do not meet an ASD diagnosis but do show atypical sensory
      behaviors to the same or greater degree as ASD children. We previously
      demonstrated that children with Sensory Processing Disorders (SPD) have impaired
      white matter microstructure, and that this white matter microstructural pathology
      correlates with atypical sensory behavior. In this study, we use diffusion tensor
      imaging (DTI) fiber tractography to evaluate the structural connectivity of
      specific white matter tracts in boys with ASD (n = 15) and boys with SPD (n =
      16), relative to typically developing children (n = 23). We define white matter
      tracts using probabilistic streamline tractography and assess the strength of
      tract connectivity using mean fractional anisotropy. Both the SPD and ASD cohorts
      demonstrate decreased connectivity relative to controls in parieto-occipital
      tracts involved in sensory perception and multisensory integration. However, the
      ASD group alone shows impaired connectivity, relative to controls, in temporal
      tracts thought to subserve social-emotional processing. In addition to these
      group difference analyses, we take a dimensional approach to assessing the
      relationship between white matter connectivity and participant function. These
      correlational analyses reveal significant associations of white matter
      connectivity with auditory processing, working memory, social skills, and
      inattention across our three study groups. These findings help elucidate the
      roles of specific neural circuits in neurodevelopmental disorders, and begin to
      explore the dimensional relationship between critical cognitive functions and
      structural connectivity across affected and unaffected children.

PMID- 25075611
TI  - The push and pull of land use policy: reconstructing 150 years of development and
      conservation land acquisition.
AB  - The growth of human populations and their resource needs have stressed the
      conservation of natural land resources. Many policies and programs have been
      implemented to address the pressures on land resources and notwithstanding this
      pressure, significant acquisition of land for conservation has occurred
      throughout history in the U.S., and internationally. Here we assess the on-the
      ground result of the evolution of land use policies in California as a pioneer
      forerunner, in the form of acquisition of land for conservation (i.e. Open
      Space), and its impact on the rest of the U.S. and beyond. To this end we
      describe the timeline and spatial representation of the growth of California's
      conservation network over the last 150 years, and link it to the history of land
      use policies. We then assess whether conservation land acquisition has
      consistently grown through time or occurred in specific decades. About 1/4 of the
      state is now designated Open Space. Fewer and larger areas conserved and acquired
      at the beginning of the 20th century; the conservation network was complemented
      with a larger number of smaller sized properties. Despite acquisition of land in
      every decade, the process was uneven (E = 0.3 for California, E = 0.14 +/- 0.08
      average for the state's counties), mostly due to the large acquisitions and land
      set asides in the 1900s, followed by 1930s and 1940s. This process was a result
      of a comprehensive set of legislation that evolved through time, and resulted
      from the competing needs for development and conservation. Even with the
      impressive 174,000 km2 of public lands in California, the future of California's
      natural infrastructure and natural heritage cannot rely solely on these public
      lands, nor public agencies and their resources. Critically a future course of
      land preservation relying on the purchase of new lands - in California and beyond
      - for conservation is tremendously expensive.

PMID- 25075612
TI  - Comprehensive Red List assessment reveals exceptionally high extinction risk to
      Madagascar palms.
AB  - The establishment of baseline IUCN Red List assessments for plants is a crucial
      step in conservation planning. Nowhere is this more important than in
      biodiversity hotspots that are subject to significant anthropogenic pressures,
      such as Madagascar. Here, all Madagascar palm species are assessed using the IUCN
      Red List categories and criteria, version 3.1. Our results indicate that 83% of
      the 192 endemic species are threatened, nearly four times the proportion
      estimated for plants globally and exceeding estimates for all other
      comprehensively evaluated plant groups in Madagascar. Compared with a previous
      assessment in 1995, the number of Endangered and Critically Endangered species
      has substantially increased, due to the discovery of 28 new species since 1995,
      most of which are highly threatened. The conservation status of most species
      included in both the 1995 and the current assessments has not changed. Where
      change occurred, more species have moved to lower threat categories than to
      higher categories, because of improved knowledge of species and their
      distributions, rather than a decrease in extinction risk. However, some cases of
      genuine deterioration in conservation status were also identified. Palms in
      Madagascar are primarily threatened by habitat loss due to agriculture and
      biological resource use through direct exploitation or collateral damage. The
      recent extension of Madagascar's protected area network is highly beneficial for
      palms, substantially increasing the number of threatened species populations
      included within reserves. Notably, three of the eight most important protected
      areas for palms are newly designated. However, 28 threatened and data deficient
      species are not protected by the expanded network, including some Critically
      Endangered species. Moreover, many species occurring in protected areas are still
      threatened, indicating that threatening processes persist even in reserves.
      Definitive implementation of the new protected areas combined with local
      community engagement are essential for the survival of Madagascar's palms. 

PMID- 25075613
TI  - Hemocompatibility and anti-biofouling property improvement of poly(ethylene
      terephthalate) via self-polymerization of dopamine and covalent graft of lysine.
AB  - Inspired by the composition of adhesive proteins in mussels, we used self
      polymerized dopamine to form a thin and surface-adherent polydopamine layer onto
      poly(ethylene terephthalate) (PET) sheet, followed by covalently grafting lysine
      (Lys) to improve hemocompatibility and anti-biofouling property. The obtained
      surfaces were characterized by water contact angle measurements, attenuated total
      reflectance Fourier transform infrared spectroscopy, and X-ray photoelectron
      spectroscopy analysis. The results of platelet adhesion and protein adsorption
      tests showed that Lys-immobilized PET was endowed with improved resistance to
      nonspecific protein adsorption and platelet adhesion. Cell assay results showed
      that PET-g-Lys surface could greatly inhibit NIH 3T3 cell adhesion. These works
      provide a facile hemocompatible and anti-fouling surface for biomedical
      applications. 

PMID- 25075615
TI  - Ignoring imperfect detection in biological surveys is dangerous: a response to
      'fitting and interpreting occupancy models'.
AB  - In a recent paper, Welsh, Lindenmayer and Donnelly (WLD) question the usefulness
      of models that estimate species occupancy while accounting for detectability. WLD
      claim that these models are difficult to fit and argue that disregarding
      detectability can be better than trying to adjust for it. We think that this
      conclusion and subsequent recommendations are not well founded and may negatively
      impact the quality of statistical inference in ecology and related management
      decisions. Here we respond to WLD's claims, evaluating in detail their arguments,
      using simulations and/or theory to support our points. In particular, WLD argue
      that both disregarding and accounting for imperfect detection lead to the same
      estimator performance regardless of sample size when detectability is a function
      of abundance. We show that this, the key result of their paper, only holds for
      cases of extreme heterogeneity like the single scenario they considered. Our
      results illustrate the dangers of disregarding imperfect detection. When ignored,
      occupancy and detection are confounded: the same naive occupancy estimates can be
      obtained for very different true levels of occupancy so the size of the bias is
      unknowable. Hierarchical occupancy models separate occupancy and detection, and
      imprecise estimates simply indicate that more data are required for robust
      inference about the system in question. As for any statistical method, when
      underlying assumptions of simple hierarchical models are violated, their
      reliability is reduced. Resorting in those instances where hierarchical occupancy
      models do no perform well to the naive occupancy estimator does not provide a
      satisfactory solution. The aim should instead be to achieve better estimation, by
      minimizing the effect of these issues during design, data collection and
      analysis, ensuring that the right amount of data is collected and model
      assumptions are met, considering model extensions where appropriate. 

PMID- 25075617
TI  - Evaluation of pharmacokinetic and pharmacodynamic properties of cimicoxib in
      fasted and fed horses.
AB  - AIMS: To determine the pharmacokinetics of cimicoxib and to assess the inhibition
      of cyclooxygenase (COX) after a 5 mg/kg, single oral administration in horses
      that were fasted or fed. METHODS: The study was conducted using an open, single
      dose (5 mg/kg), two treatment (fasted and fed), two-period, crossover design with
      a 2-week interval between dosages. Six healthy mares received 5 mg/kg of
      cimicoxib via nasogastric tube after fasting for 12 hours, or 2 hours after
      feeding. After administration, blood samples were collected for up to 24 hours
      and plasma used for pharmacokinetic analysis. Additional serum and plasma samples
      were used to measure concentrations of thromboxane B2 (TXB2) and prostaglandin E2
      (PGE2), to assess COX-1 and -2 inhibition, respectively. RESULTS: Following
      cimicoxib administration, the mean maximum plasma concentration was 0.16 (SD
      0.01) ug/mL and 0.14 (SD 0.03) ug/mL in fasted and fed groups, respectively. The
      mean time taken to reach maximum plasma concentration was longer in the fed group
      (5.91 (SD 3.23) hours) compared with the fasted group (3.25 (SD 1.17) hours), but
      this difference was not significant (p=0.12). The mean maximal inhibition of TXB2
      was 62.4 (SD 13.8)% and 54.6 (SD 15.4)%, and of PGE2 was 72.1 (SD 43.3)% and 68.5
      (SD 24.4)%, in fasted and fed horses, respectively. CONCLUSION: In the present
      study, although the COX-2 selective action of cimicoxib was not apparent, a
      relatively low concentration of cimicoxib resulted in both COX-1 and -2
      inhibition in horses. Further investigations are required to establish an optimal
      dosage regimen and safety profile before clinical trials are initiated.

PMID- 25075616
TI  - SNP@lincTFBS: an integrated database of polymorphisms in human LincRNA
      transcription factor binding sites.
AB  - Large intergenic non-coding RNAs (lincRNAs) are a new class of functional
      transcripts, and aberrant expression of lincRNAs was associated with several
      human diseases. The genetic variants in lincRNA transcription factor binding
      sites (TFBSs) can change lincRNA expression, thereby affecting the susceptibility
      to human diseases. To identify and annotate these functional candidates, we have
      developed a database SNP@lincTFBS, which is devoted to the exploration and
      annotation of single nucleotide polymorphisms (SNPs) in potential TFBSs of human
      lincRNAs. We identified 6,665 SNPs in 6,614 conserved TFBSs of 2,423 human
      lincRNAs. In addition, with ChIPSeq dataset, we identified 139,576 SNPs in
      304,517 transcription factor peaks of 4,813 lincRNAs. We also performed
      comprehensive annotation for these SNPs using 1000 Genomes Project datasets
      across 11 populations. Moreover, one of the distinctive features of SNP@lincTFBS
      is the collection of disease-associated SNPs in the lincRNA TFBSs and SNPs in the
      TFBSs of disease-associated lincRNAs. The web interface enables both flexible
      data searches and downloads. Quick search can be query of lincRNA name, SNP
      identifier, or transcription factor name. SNP@lincTFBS provides significant
      advances in identification of disease-associated lincRNA variants and improved
      convenience to interpret the discrepant expression of lincRNAs. The SNP@lincTFBS
      database is available at http://bioinfo.hrbmu.edu.cn/SNP_lincTFBS. 

PMID- 25075618
TI  - Subsidies and the survival of the ACA--divided decisions on premium tax credits.

PMID- 25075619
TI  - Reforming the financing and governance of GME.

PMID- 25075620
TI  - Innovation in medical education.

PMID- 25075621
TI  - Adaptive neuro-fuzzy methodology for noise assessment of wind turbine.
AB  - Wind turbine noise is one of the major obstacles for the widespread use of wind
      energy. Noise tone can greatly increase the annoyance factor and the negative
      impact on human health. Noise annoyance caused by wind turbines has become an
      emerging problem in recent years, due to the rapid increase in number of wind
      turbines, triggered by sustainable energy goals set forward at the national and
      international level. Up to now, not all aspects of the generation, propagation
      and perception of wind turbine noise are well understood. For a modern large wind
      turbine, aerodynamic noise from the blades is generally considered to be the
      dominant noise source, provided that mechanical noise is adequately eliminated.
      The sources of aerodynamic noise can be divided into tonal noise, inflow
      turbulence noise, and airfoil self-noise. Many analytical and experimental
      acoustical studies performed the wind turbines. Since the wind turbine noise
      level analyzing by numerical methods or computational fluid dynamics (CFD) could
      be very challenging and time consuming, soft computing techniques are preferred.
      To estimate noise level of wind turbine, this paper constructed a process which
      simulates the wind turbine noise levels in regard to wind speed and sound
      frequency with adaptive neuro-fuzzy inference system (ANFIS). This intelligent
      estimator is implemented using Matlab/Simulink and the performances are
      investigated. The simulation results presented in this paper show the
      effectiveness of the developed method. 

PMID- 25075622
TI  - Transient humoral protection against H5N1 challenge after seasonal influenza
      vaccination of humans.
AB  - Current influenza vaccines are believed to confer protection against a narrow
      range of virus strains. The identification of broadly influenza neutralizing
      antibodies (bnAbs) has triggered efforts to develop vaccines providing
      'universal' protection against influenza. Several bnAbs were isolated from humans
      recently vaccinated with conventional influenza vaccines, suggesting that such
      vaccines could, in principle, be broadly protective. Assessing the breadth-of
      protection conferred to humans by influenza vaccines is hampered by the lack of
      in vitro correlates for broad protection. We designed and employed a novel human
      to-mouse serum transfer and challenge model to analyze protective responses in
      serum samples from clinical trial subjects. One dose of seasonal vaccine induces
      humoral protection not only against vaccine-homologous H1N1 challenge, but also
      against H5N1 challenge. This heterosubtypic protection is neither detected, nor
      accurately predicted by in vitro immunogenicity assays. Moreover, heterosubtypic
      protection is transient and not boosted by repeated inoculations. Strategies to
      increase the breadth and duration of the protective response against influenza
      are required to obtain 'universal' protection against influenza by vaccination.
      In the absence of known correlates of protection for broadly protective vaccines,
      the human-to-mouse serum transfer and challenge model described here may aid the
      development of such vaccines. 

PMID- 25075623
TI  - Pre-hospital risk factors for inpatient death from severe febrile illness in
      Malian children.
AB  - BACKGROUND: Inpatient case fatality from severe malaria remains high in much of
      sub-Saharan Africa. The majority of these deaths occur within 24 hours of
      admission, suggesting that pre-hospital management may have an impact on the risk
      of case fatality. METHODS: Prospective cohort study, including questionnaire
      about pre-hospital treatment, of all 437 patients admitted with severe febrile
      illness (presumed to be severe malaria) to the paediatric ward in Sikasso
      Regional Hospital, Mali, in a two-month period. FINDINGS: The case fatality rate
      was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were
      associated with significantly higher mortality. In multiple logistic regression
      models and in a survival analysis to examine pre-admission risk factors for case
      fatality, the only consistent and significant risk factor was sex. Girls were
      twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide
      variety of pre-hospital treatments used, both modern and traditional. None had a
      consistent impact on the risk of death across different analyses. Reported use of
      traditional treatments was not associated with post-admission outcome.
      INTERPRETATION: Aside from well-recognised markers of severity, the main risk
      factor for death in this study was female sex, but this study cannot determine
      the reason why. Differences in pre-hospital treatments were not associated with
      case fatality.

PMID- 25075624
TI  - Effects of nitrogen and phosphorus fertilization on soil carbon fractions in
      alpine meadows on the Qinghai-Tibetan Plateau.
AB  - In grassland ecosystems, N and P fertilization often increase plant productivity,
      but there is no concensus if fertilization affects soil C fractions. We tested
      effects of N, P and N+P fertilization at 5, 10, 15 g m-2 yr-1 (N5, N10, N15, P5,
      P10, P15, N5P5, N10P10, and N15P15) compared to unfertilized control on soil C,
      soil microbial biomass and functional diversity at the 0-20 cm and 20-40 cm depth
      in an alpine meadow after 5 years of continuous fertilization. Fertilization
      increased total aboveground biomass of community and grass but decreased legume
      and forb biomass compared to no fertilization. All fertilization treatments
      decreased the C:N ratios of legumes and roots compared to control, however
      fertilization at rates of 5 and 15 g m-2 yr-1 decreased the C:N ratios of the
      grasses. Compared to the control, soil microbial biomass C increased in N5, N10,
      P5, and P10 in 0-20 cm, and increased in N10 and P5 while decreased in other
      treatments in 20-40 cm. Most of the fertilization treatments decreased the
      respiratory quotient (qCO2) in 0-20 cm but increased qCO2 in 20-40 cm.
      Fertilization increased soil microbial functional diversity (except N15) but
      decreased cumulative C mineralization (except in N15 in 0-20 cm and N5 in 20-40
      cm). Soil organic C (SOC) decreased in P5 and P15 in 0-20 cm and for most of the
      fertilization treatments (except N15P15) in 20-40 cm. Overall, these results
      suggested that soils will not be a C sink (except N15P15). Nitrogen and
      phosphorus fertilization may lower the SOC pool by altering the plant biomass
      composition, especially the C:N ratios of different plant functional groups, and
      modifying C substrate utilization patterns of soil microbial communities. The N+P
      fertilization at 15 g m-2 yr-1 may be used in increasing plant aboveground
      biomass and soil C accumulation under these meadows. 

PMID- 25075625
TI  - A rare association of celiac disease and aplastic anemia: case report of a child
      and review of literature.
AB  - An association between severe aplastic anemia and other autoimmune diseases is
      rare and has been described in adults for eosinophilic fasciitis, thymomas,
      systemic lupus erythematosus, and thyroid disorders. Herein we report a patient
      with celiac disease who was not strictly following a gluten-free diet and
      presented with progressive pallor, fever, and weakness of 1 month's duration. On
      investigation, he had pancytopenia, which on subsequent evaluation revealed
      aplastic anemia. An association between aplastic anemia and celiac disease has
      rarely been reported. To the best of author's knowledge, only 1 pediatric case of
      celiac disease associated with aplastic anemia has been published. This is the
      second report to suggest such an association in children.

PMID- 25075626
TI  - Chitooligosaccharides prevent osteopenia by promoting bone formation and
      suppressing bone resorption in ovariectomised rats: possible involvement of COX
      2.
AB  - Chitooligosaccharides (CHOS) added in diet have been found as potent calcium
      fortifiers in conditions of Ca(2+) deficiency such as osteoporosis. In this
      study, we found that pharmaceutical intervention using CHOS prevented ovariectomy
      (OVX)-induced bone mineral density loss and the deterioration of trabecular
      microarchitecture in a dose-dependent manner (p < 0.05 or 0.01). CHOS (125, 250
      mg/kg) suppressed the serum levels of bone resorption biomarkers CTx and TRACP5b
      induced by OVX (p < 0.05), but increased the levels of osteogenic markers ALP and
      OC by 11.3-11.6% and 10.7-15.2% of OVX group (p < 0.05), suggesting the exact
      pharmacological action of CHOS in the control of osteoporosis which may be the
      result of both promoting bone formation and suppressing bone resorption. Bone
      turnover-modulating effects of CHOS appear related to their anti-inflammatory
      capacity to down-regulate mRNA and protein expression of COX-2 (17.2-32.2% and
      16.4-21.9% of OVX group, p < 0.05 or 0.01), a key mediator linking between
      inflammation and osteoporosis.

PMID- 25075627
TI  - Characterizing the empirical distribution of prokaryotic genome n-mers in the
      presence of nullomers.
AB  - Characterizing the empirical distribution of the frequency of n-mers is a vital
      step in understanding the entire genome. This will allow for researchers to
      examine how complex the genome really is, and move beyond simple, traditional
      modeling frameworks that are often biased in the presence of abundant and/or
      extremely rare words. We hypothesize that models based on the negative binomial
      distribution and its zero-inflated counterpart will characterize the n-mer
      distributions of genomes better than the Poisson. Our study examined the
      empirical distribution of the frequency of n-mers (6 <= n <= 11) in 2,199
      genomes. We considered four distributions: Poisson, negative binomial, zero
      inflated Poisson, and zero-inflated negative binomial (ZINB). The number of
      genomes that have nullomers in 6-, 7-, and 8-mers was 150, 602 and 2,012,
      respectively, whereas all of the genomes for the 9-, 10-, and 11-mers had
      nullomers. In each n-mer considered, the negative binomial model performed the
      best for at least 93% of the 2,199 genomes; however, a small percentage (i.e.,
      <7%) of the genomes did prefer the ZINB. The negative binomial and zero-inflation
      distributions extend the traditional Poisson setting and are more flexible in
      handling overdispersion that can be caused by an increase in nullomers. In an
      effort to characterize the distribution of the frequency of n-mers, researchers
      should also consider other discrete distributions that are more flexible and
      adjust for possible overdispersion.

PMID- 25075628
TI  - Highly biocompatible zwitterionic phospholipids coated upconversion nanoparticles
      for efficient bioimaging.
AB  - The potential of upconversion nanoparticles (UCNPs) in various biomedical
      applications, including immunoassays, biomedical imaging, and molecular sensing,
      requires their surface derivatized to be hydrophilic and biocompatible. Here, a
      new family of compact zwitterionic ligand systems composed with functional
      phospholipids was designed and used for the surface modification of UCNPs. The
      zwitterionic UCNPs are hydrophilic, compact, and easily functionalized. It was
      proved that zwitterionic phospholipids could provide UCNPs with not only extended
      pH and salt stability but also little nonspecific interactions to positively and
      negatively charged proteins, low nonspecific adhesion in live-cell imaging
      process. Most notably, the efficient in vivo tumor imaging performance and long
      blood circulation half-life suggests the excellent biocompatibility for in vivo
      imaging of the zwitterionic UCNPs. 

PMID- 25075629
TI  - Neonatal pertussis, cocooning and maternal immunization.
AB  - The rising incidence of whooping cough, a highly contagious infection caused by
      Bordetella pertussis, is particularly significant for young infants who have the
      highest risk for morbidity and mortality. The pertussis resurgence has led to a
      shift in primary prevention relying on childhood vaccination to a cocooning
      strategy, that is, vaccination of close contacts of newborn infants (new mothers,
      fathers, grandparents, siblings, caretakers, etc.), thereby reducing pertussis
      exposure. Immunization of women during pregnancy rather than during the immediate
      postpartum period (the initial cocooning recommendation) appears to be a better
      approach by directly providing protection through transplacental transfer of
      maternal vaccine-induced antibodies. This article describes neonatal pertussis,
      cocooning as a means of reducing neonatal exposure to pertussis and maternal
      immunization as a means of protecting young infants against pertussis infection. 

PMID- 25075630
TI  - Graphene frameworks promoted electron transport in quantum dot-sensitized solar
      cells.
AB  - Graphene frameworks (GFs) were incorporated into TiO2 photoanode as electron
      transport medium to improve the photovoltaic performance of quantum dot
      sensitized solar cells (QDSSCs) for their excellent conductivity and isotropic
      framework structure that could permit rapid charge transport. Intensity modulated
      photocurrent/photovoltage spectroscopy and electrochemical impedance spectroscopy
      results show that the electron transport time (tau(d)) of 1.5 wt % GFs/TiO2
      electrode is one-fifth of that of the TiO2 electrode, and electron lifetime
      (tau(n)) and diffusion path length (Ln) are thrice those of the TiO2 electrode.
      Results also revealed that the GFs/TiO2 electrode has a shorter electron
      transport time (tau(d)), as well as longer electron lifetime (tau(n)) and
      diffusion path length (Ln), than conventional 2D graphene sheets/TiO2 electrode,
      thus indicating that GFs could promote rapid electron transfer in TiO2
      photoanodes. Photocurrent-voltage curves demonstrated that when incorporating 1.5
      wt % GFs into TiO2 photoanode, a maximum power conversion efficiency of 4.2% for
      QDSSCs could be achieved. This value was higher than that of TiO2 photoanode and
      2D graphene sheets/TiO2 electrode. In addition, the reasons behind the
      sensitivity of photoelectric conversion efficiency to the graphene concentration
      in the TiO2 were also systematically investigated. Our results provide a basic
      understanding of how GFs can efficiently promote electron transport in TiO2-based
      solar cells.

PMID- 25075631
TI  - Betalain profile, phenolic content, and color characterization of different parts
      and varieties of Opuntia ficus-indica.
AB  - Three different varieties of Opuntia ficus-indica (R, red; Y, yellow; RY, red
      yellow) have been considered in this study. Attention was focused on differential
      tristimulus colorimetry and on the analysis of individual betalains (HPLC-DAD-ESI
      ToF-MS) and phenolic content, scarcely previously reported in these kinds of
      samples. The importance of this research stems from the elucidation of the parts
      and varieties of cactus pear more optimal for use as natural colorants and
      sources of phenolics and betalains. Thus, the RY pulp was appropriate to obtain
      colorants with high color intensity (C*(ab) = 66.5), whereas the whole Y fruit
      and R pulp reached powerful and stable yellow and red colors, respectively
      (C*(ab)/h(ab), 57.1/84.7 and 61.1 degrees /81.8 degrees ). This choice was also
      based on the visually appreciable differences (DeltaE*(ab) > 5) among samples,
      mainly quantitative (%Delta(2)L, %Delta(2)C). In addition, seeds of all Opuntia
      varieties showed significantly (p < 0.05) similar phenolic content (around 23.3
      mg/g) and color characteristics.

PMID- 25075633
TI  - Cu(I)-catalyzed cross-coupling of conjugated ene-yne-ketones and terminal
      alkynes: synthesis of furan-substituted allenes.
AB  - A new method for the synthesis of furan-substituted allenes via Cu(I)-catalyzed
      coupling of conjugated ene-yne-ketones with terminal alkynes has been developed.
      A wide range of functional groups are tolerated, and the products are obtained in
      good to excellent yields under mild conditions. A copper carbene migratory
      insertion is proposed as the key step in this transformation with conjugated ene
      yne-ketones as carbene precursors. 

PMID- 25075632
TI  - Inhibiting epidermal growth factor receptor at a distance.
AB  - The epidermal growth factor receptor (EGFR) tyrosine kinase is implicated in a
      large number of human cancers. Most EGFR inhibitors target the extracellular,
      growth factor-binding domain or the intracellular, ATP-binding domain. Here we
      describe molecules that inhibit the kinase activity of EGFR in a new way, by
      competing with formation of an essential intradimer coiled coil containing the
      juxtamembrane segment from each member of the receptor partnership. The most
      potent molecules we describe bind EGFR directly, decrease the proliferation of
      wild-type and mutant EGFR-dependent cells lines, inhibit phosphorylation of EGFR
      and downstream targets, and block coiled coil formation as judged by bipartite
      tetracysteine display. Potency is directly correlated with the ability to block
      coiled coil formation within full-length EGFR in cells. 

PMID- 25075634
TI  - Catalytic acceptorless dehydrogenative coupling of arylhydrazines and alcohols
      for the synthesis of arylhydrazones.
AB  - The direct synthesis of arylhydrazones via catalytic acceptorless dehydrogenative
      coupling of arylhydrazines and alcohols has been accomplished. More importantly,
      complete selectivity for arylhydrazones and none of the N-alkylated byproducts
      were generated in this process, which exhibit new potential and provide a new
      horizon for the development of catalytic acceptorless dehydrogenative coupling
      reactions. 

PMID- 25075635
TI  - Coating two-dimensional nanomaterials with metal-organic frameworks.
AB  - We demonstrate the coating of various 2D nanomaterials including MoS2 nanosheets,
      graphene oxide (GO), and reduced graphene oxide (rGO) with zeolitic imidazolate
      frameworks (i.e., ZIF-8) via a facile procedure. Additionally, ternary core-shell
      structures like Pt-MoS2@ZIF-8, Pt-GO@ZIF-8, and Pt-rGO@ZIF-8 have also been
      prepared. As a proof-of-concept application, a memory device based on MoS2@ZIF-8
      hybrid was fabricated and it exhibited write-once-read-many-times (WORM) memory
      effect with high ON/OFF ratio and long operating lifetime. It is expected that
      MOF coated 2D nanomaterials may find wide applications in energy storage and
      conversion, catalysis, sensing, and information storage devices. 

PMID- 25075636
TI  - New class of scorpionate: tris(tetrazolyl)-iron complex and its different
      coordination modes for alkali metal ions.
AB  - We report formation of a new metallascorpionate ligand, [FeL3](3-) (IPtz),
      containing a Fe core and three 5-(2-hydroxyphenyl)-1H-tetrazole (LH2) ligands. It
      features two different binding sites, oxygen and nitrogen triangles, which
      consist of three oxygen or nitrogen donors from tetrazole. The binding affinities
      of the complex for three alkali metal ions were studied using UV
      spectrophotometry titrations. All three alkali metal ions show high affinities
      and binding constants (>3 * 10(6) M(-1)), based on the 1:1 binding isotherms to
      IPtz. The coordination modes of the alkali metals and IPtz in the solid were
      studied using X-ray crystallography; two different electron-donor sites show
      different coordination numbers for Li(+), Na(+), and K(+) ions. The oxygen
      triangles have the kappa(2) coordination mode with Li(+) and kappa(3)
      coordination mode with Na(+) and K(+) ions, whereas the nitrogen triangles show
      kappa(3) coordination with K(+) only. The different binding affinities of IPtz in
      the solid were manipulated using multiple metal precursors. A Fe-K-Zn trimetallic
      complex was constructed by assembly of an IPtz ligand, K, and Zn precursors and
      characterized using X-ray crystallography. Oxygen donors are coordinated with the
      K ion via the kappa(3) coordination mode, and nitrogen donors are coordinated
      with Zn metal by kappa(3) coordination. The solid-state structure was confirmed
      to be a honeycomb coordination polymer with a one-dimensional infinite metallic
      array, i.e., -(K-K-Fe-Zn-Fe-K)n-. 

PMID- 25075637
TI  - Antibodies against MERS coronavirus in dromedary camels, Kenya, 1992-2013.
AB  - Dromedary camels are a putative source for human infections with Middle East
      respiratory syndrome coronavirus. We showed that camels sampled in different
      regions in Kenya during 1992-2013 have antibodies against this virus. High
      densities of camel populations correlated with increased seropositivity and might
      be a factor in predicting long-term virus maintenance. 

PMID- 25075638
TI  - N-[6-(4-butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4
      methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a novel
      intravenous and oral, reversible, and directly acting P2Y12 antagonist.
AB  - In the search of a potential backup for clopidogrel, we have initiated a HTS
      campaign designed to identify novel reversible P2Y12 antagonists. Starting from a
      hit with low micromolar binding activity, we report here the main steps of the
      optimization process leading to the identification of the preclinical candidate
      SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor
      antagonist and by far the most potent inhibitor of ADP-induced platelet
      aggregation among the P2Y12 antagonists described in the literature. SAR216471
      displays potent in vivo antiplatelet and antithrombotic activities and has the
      potential to differentiate from other antiplatelet agents. 

PMID- 25075639
TI  - A Rac1-independent role for P-Rex1 in melanoblasts.

PMID- 25075640
TI  - Characterization of selenium in ambient aerosols and primary emission sources.
AB  - Atmospheric selenium (Se) in aerosols was investigated using X-ray absorption
      near-edge structure (XANES) spectroscopy and X-ray fluorescence (XRF) microscopy.
      These techniques were used to determine the oxidation state and elemental
      associations of Se in common primary emission sources and ambient aerosols
      collected from the greater Atlanta area. In the majority of ambient aerosol and
      primary emission source samples, the spectroscopic patterns as well as the
      absence of elemental correlations suggest Se is in an elemental, organic, or
      oxide form. XRF microscopy revealed numerous Se-rich particles, or hotspots,
      accounting on average for ~16% of the total Se in ambient aerosols. Hotspots
      contained primarily Se(0)/Se(-II). However, larger, bulk spectroscopic
      characterizations revealed Se(IV) as the dominant oxidation state in ambient
      aerosol, followed by Se(0)/Se(-II) and Se(VI). Se(IV) was the only observed
      oxidation state in gasoline, diesel, and coal fly ash, while biomass burning
      contained a combination of Se(0)/Se(-II) and Se(IV). Although the majority of Se
      in aerosols was in the most toxic form, the Se concentration is well below the
      California Environmental Protection Agency chronic exposure limit (~20000
      ng/m(3)). 

PMID- 25075642
TI  - The role of macrophage 1 antigen in polymicrobial sepsis.
AB  - PURPOSE: Macrophage 1 antigen (Mac-1, CD11bCD18) is a leukocyte adhesion molecule
      that is involved in many functions including leukocyte recruitment, phagocytosis,
      and neutrophil apoptosis. The previous report of mild polymicrobial, abdominal
      sepsis showed that the administration of anti-CD11b-blocking antibody
      administration attenuated lung injury without any survival benefit. Here we
      tested the impact of Mac-1 deficiency in severe polymicrobial abdominal sepsis
      model. METHODS: Polymicrobial sepsis was studied using cecal ligation and
      puncture model in wild-type (WT) or Mac-1-deficient (CD11b knockout [KO]) mice,
      and their outcomes were examined. Bacterial tissue load and the recruitment of
      neutrophils to the abdominal cavity were assessed. In vitro bacterial killing
      assay was performed. Serum cytokine levels were measured using multiarray.
      Apoptosis of spleen tissues was assessed using Western blot analysis and
      immunohistochemistry (cleaved caspase 3 and TUNEL staining). In addition, in
      vitro apoptosis assay was performed using primary splenocytes from both WT and KO
      mice. The recruitment of neutrophils to lung was assessed by measuring
      myeloperoxidase activity. RESULTS: Macrophage 1 antigen deficiency significantly
      decreased survival (survival percentage WT 43.5% vs. KO 13.0%; P = 0.0038) with
      higher bacterial load in blood and more severe systemic inflammation. Knockout
      mice demonstrated higher apoptosis both in vivo and in vitro. The recruitment of
      neutrophils to lung was not different between WT and KO mice. CONCLUSIONS:
      Macrophage 1 antigen deficiency was associated with poorer outcomes, more
      bacterial load, systemic inflammation, and splenic apoptosis. However, Mac-1
      deficiency did not attenuate neutrophil recruitment to lung.

PMID- 25075641
TI  - Interactions of protein kinase C-alpha C1A and C1B domains with membranes: a
      combined computational and experimental study.
AB  - Protein kinase C-alpha (PKCalpha) has been studied widely as a paradigm for
      conventional PKCs, with two C1 domains (C1A and C1B) being important for the
      regulation and function of the kinase. However, it is challenging to explore
      these domains in membrane-bound environments with either simulations or
      experiments alone. In this work, we have combined modeling, simulations, and
      experiments to understand the molecular basis of the PKCalpha C1A and C1B domain
      interactions with membranes. Our atomistic simulations of the PKCalpha C1 domains
      reveal the dynamic interactions of the proteins with anionic lipids, as well as
      the conserved hydrogen bonds and the distinct nonpolar contacts formed with lipid
      activators. Corroborating evidence is obtained from additional simulations and
      experiments in terms of lipid binding and protein diffusion. Overall, our study,
      for the first time, explains with atomistic detail how the PKCalpha C1A and C1B
      domains interact differently with various lipids. On the molecular level, the
      information provided by our study helps to shed light on PKCalpha regulation and
      activation mechanism. The combined computational/experimental approach
      demonstrated in this work is anticipated to enable further studies to explore the
      roles of C1 domains in many signaling proteins and to better understand their
      molecular mechanisms in normal cellular function and disease development. 

PMID- 25075643
TI  - Association between microstructural integrity of frontostriatal tracts and school
      functioning: ADHD symptoms and executive function as mediators.
AB  - BACKGROUND: Deficits in executive function (EF), impaired school functioning and
      altered white matter integrity in frontostriatal networks have been associated
      with attention-deficit/hyperactivity disorder (ADHD). However, relationships
      between impairments in these areas are unclear. Using a sample of youths with and
      without ADHD, this study examined the association between microstructural
      integrity of frontostriatal tracts and school dysfunction and the mediating roles
      of EF and ADHD symptoms in this association. METHOD: The sample included 32
      Taiwanese youths with ADHD and 32 age-, sex-, handedness- and IQ-matched
      typically-developing (TD) youths. Participants were assessed using psychiatric
      interviews, parent reports on ADHD symptoms and school functioning, and EF
      measures from the Cambridge Neuropsychological Test Automated Battery (CANTAB).
      The frontostriatal tracts were reconstructed by diffusion spectrum imaging (DSI)
      tractography and were subdivided into four functionally distinct segments:
      caudate-dorsolateral, caudate-medial prefrontal, caudate-orbitofrontal and
      caudate-ventrolateral tracts. RESULTS: Youths with ADHD, relative to TD youths,
      showed altered white matter integrity in all four bilateral pairs of
      frontostriatal tracts (decreased general fractional anisotropy, GFA), had poor
      attention, vigilance and response inhibition, and showed impaired school
      functioning. Altered microstructural integrity in frontostriatal tracts was
      significantly associated with school dysfunction, which was mediated by EF
      measures of attention/vigilance and response inhibition in addition to
      inattention and hyperactivity symptoms. CONCLUSIONS: Our findings demonstrate an
      association between white matter integrity in the frontostriatal networks and
      school functioning and suggest that EF deficits and ADHD symptoms may be the
      mediating mechanisms for this association. Future research is needed to test the
      directionality and specificity of this finding.

PMID- 25075644
TI  - Children's perspective on health-related quality of life during active treatment
      for acute lymphoblastic leukemia: an advanced content analysis approach.
AB  - BACKGROUND: Qualitative research provides insight into the cancer experience
      through the perspective of the pediatric patient. However, somewhat small sample
      sizes can hinder full discovery of new knowledge and limit interpretation of
      data. OBJECTIVE: The objective of this study was to describe health-related
      quality of life (HRQOL) reported by children and adolescents in responses to 2
      interview questions during treatment for acute lymphoblastic leukemia (ALL) and
      compare their responses by age, gender, risk group, and time in treatment through
      a quantitative content analysis approach. METHODS: Children and adolescents (N =
      150) were asked 2 validated questions in pediatric patients receiving treatment
      for ALL: "What makes a good day for you?" and "How has being sick been for you?"
      over 6 treatment time points. Interview data were coded analyzed quantitatively.
      RESULTS: Code frequencies differed significantly by age, gender, risk group, and
      time in treatment. Adolescents had a greater focus on being with friends, and
      females generally reported more codes representing negative experiences. Children
      and adolescents reported being affected by symptoms resulting from cancer
      treatment. Some adolescents described that being sick positively changed their
      lives and viewed their illness as a new life experience. CONCLUSION: The 2
      proposed questions are feasible to use clinically to assess HRQOL in children and
      adolescents with ALL, and the qualitative codes from their descriptions can be
      used to identify factors affecting HRQOL of children and adolescents with
      leukemia. IMPLICATIONS FOR PRACTICE: Nurses can use these 2 questions to assess
      the HRQOL of children and adolescents during and following treatment for ALL.

PMID- 25075645
TI  - Protocol Paper: A Randomized Trial of 2 Creams in the Skin Care of Patients
      Receiving Radiation Therapy for Breast Cancer in the Tropics.
AB  - BACKGROUND: Nurses working in a northern Australia Radiation Therapy Unit advise
      all patients undergoing radiation therapy to use a readily available
      nonprescription moisturizing cream to minimize the severity of radiation skin
      reactions. However, patients report that the cream is thick and difficult to use
      in the humid tropical climate, and nurses anecdotally suspect an increase in
      severe skin reactions during the summer months. OBJECTIVE: This article presents
      the protocol for a randomized controlled trial that addressed a lack of evidence
      pertaining to the use of topical creams to prevent acute radiation skin reactions
      in a tropical climate. METHODS: Two skin care creams were used in the trial. The
      trial's primary outcome measure was the incidence of moist desquamation during
      treatment and 1 month after treatment completion. The secondary outcome was the
      participants' acceptance of the allocated cream at similar time points. RESULTS:
      Recruitment to the trial has been completed. Findings of the research will be
      reported in a separate publication. CONCLUSIONS: This article presents the
      protocol for a randomized controlled trial that addresses a lack of evidence
      pertaining to the use of topical creams to prevent acute radiation skin reactions
      in a tropical climate. IMPLICATIONS FOR PRACTICE: This protocol can be adapted by
      other researchers conducting practice-based research.

PMID- 25075646
TI  - Anxiety sensitivity in bereaved adults with and without complicated grief.
AB  - Complicated grief (CG) is a bereavement-specific syndrome chiefly characterized
      by symptoms of persistent separation distress. Physiological reactivity to
      reminders of the loss and repeated acute pangs or waves of severe anxiety and
      psychological pain are prominent features of CG. Fear of this grief-related
      physiological arousal may contribute to CG by increasing the distress associated
      with grief reactions and increasing the likelihood of maladaptive coping
      strategies and grief-related avoidance. Here, we examined anxiety sensitivity
      (AS; i.e., the fear of anxiety-related sensations) in two studies of bereaved
      adults with and without CG. In both studies, bereaved adults with CG exhibited
      elevated AS relative to those without CG. In study 2, AS was positively
      associated with CG symptom severity among those with CG. These findings are
      consistent with the possibility that AS contributes to the development or
      maintenance of CG symptoms. 

PMID- 25075647
TI  - Twitter psychosis: a rare variation or a distinct syndrome?
AB  - The authors report the development of psychosis in a young woman coinciding with
      excessive use of the online communication system Twitter and the results of an
      experimental account to argue that Twitter may have a high potential to induce
      psychosis in predisposed users. 

PMID- 25075648
TI  - A short history of Thrombosis and Hemostasis: part I (40th year celebratory
      issue).

PMID- 25075649
TI  - The old and the new in prekallikrein deficiency: historical context and a family
      from Argentina with PK deficiency due to a new mutation (Arg541Gln) in exon 14
      associated with a common polymorphysm (Asn124Ser) in exon 5.
AB  - Prekallikrein (PK) is one of the clotting factors involved in the contact phase
      of blood. PK has an important historical role as its deficiency state represents
      the second instance of a clotting defect without bleeding manifestations, the
      first one being factor XII deficiency. PK deficiency is a rare clotting disorder.
      Moreover, only 11 patients have been investigated so far by molecular biology
      techniques. In this article, we briefly review some of the history around PK and
      also present some recent data on a newly identified family from Argentina
      suffering from PK deficiency. Two patients are homozygous whereas other family
      members are heterozygous. PK activity and antigen are 1% of normal in the
      homozygotes and around 60 to 70% of normal in the heterozygotes. As expected, all
      patients are asymptomatic of bleeding or thrombosis presentations. However, the
      two homozygotes showed essential hypertension. The PK deficiency in this family
      is due to a new mutation (Arg541Gln) in exon 14. The defect segregates together
      with a known polymorphism, Asn124Ser, in exon 5. The significance of the presence
      of hypertension in the two homozygotes is discussed in view of the extra
      coagulation effects of PK on vasodilation, vessel permeability, and the control
      of blood pressure. Structure function analysis indicates that the substitution of
      Arg with Gln probably impedes the transmembrane diffusion of the molecule, which
      therefore cannot be secreted in the homozygotes. The presence of hypertension in
      patients with PK deficiency has been previously reported in some but not all
      patients. Future research activities will probably concentrate on the effect of
      PK and other contact phase factors on the vascular system.

PMID- 25075653
TI  - The study of chronic pancreatitis epidemiology - the big challenge.

PMID- 25075652
TI  - Thermally-induced miniaturization for micro- and nanofabrication: progress and
      updates.
AB  - The field of micro- and nanofabrication has developed extensively in the past
      several decades with rising interest in alternative fabrication techniques.
      Growth of these areas has been driven by needs that remain unaddressed by
      traditional lithographical methods: inexpensive, upscalable, biocompatible, and
      easily integrated into complete lab-on-a-chip (LOC) systems. Shape memory
      polymers (SMPs) have been explored as an alternative substrate. This review first
      focuses on structure fabrication at the micron and nanoscale using specifically
      heat-shrinkable SMPs and highlights the innovative improvements to this
      technology in the past several years. The second part of the review illustrates
      demonstrated applications of these micro- and nanostructures fabricated from heat
      shrinkable SMP films. The review concludes with a discussion about future
      prospects of heat-shrinkable SMP structures for integration into LOC systems. 

PMID- 25075654
TI  - A Spanish multicenter study to estimate the prevalence and incidence of chronic
      pancreatitis and its complications.
AB  - BACKGROUND AND OBJECTIVE: No nation-wide epidemiological study on the incidence
      and prevalence of chronic pancreatitis (CP) had been thus far carried out in
      Spain. Our goal is to estimate the prevalence and incidence of CP, as well as to
      determine the diagnostic and therapeutic criteria used in Spanish pancreas units.
      METHODS: An observational, descriptive study of hospital pancreas units in Spain.
      CP-related epidemiology, etiology, manifestations, diagnostic tests, functional
      complications, and treatments were all assessed using a structured questionnaire.
      Overall results were estimated by weighting cases in each site. RESULTS:
      Information was collected from six pancreas units with a sample frame of
      1,900,751 inhabitants. Overall prevalence was 49.3 cases per 105 population (95 %
      CI, 46 to 52) and incidence was 5.5 cases per 105 inhabitant-years (95 % CI, 5.4
      to 5.6). Most common etiologies included tobacco and alcoholism, which were
      associated with three in every four cases. The most prevalent symptoms were
      recurring pain (48.8 %) and chronic abdominal pain (30.6 %). The most widely used
      diagnostic method was echoendoscopy (79.8 %), CT (computerized tomography) (58.7
      %), and MRI (magnetic resonance imaging)/MRCP (magnetic resonance
      cholangiopancreatography) (55.9 %). Most prevalent morphologic findings included
      calcifications (35 %) and pseudocysts (27 %). Exocrine (38.8 %) and endocrine
      (35.2 %) pancreatic insufficiency had both a similar frequency. Treatments used
      were rather heterogeneous among sites, with enzyme replacement therapy (40.7 %)
      and insulin (30.9 %) being most commonly used. CONCLUSIONS: Pancreas units amass
      a significant number of both prevalent and incident CP cases. Patients seen in
      these units share a similar typology, and differences between units are greater
      regarding diagnostic and therapeutic strategies.

PMID- 25075655
TI  - Hepatotoxicity associated with statin use: analysis of the cases included in the
      Spanish Hepatotoxicity Registry.
AB  - OBJECTIVES: The hepatotoxic potential of statins is controversial. The objectives
      of this study were to describe the relative frequency of hepatotoxicity caused by
      statins and the phenotypes found in Spain. PATIENTS AND METHODS: The incidence of
      hepatotoxicity attributed to statins in the Spanish Hepatotoxicity Registry (REH)
      were studied and compared with those attributed to other drugs. RESULTS: Between
      April 1994 and August 2012, the REH included a total of 858 cases of which 47
      (5.5 %) were attributed to statins. Of these, 16 were due to atorvastatin (34 %);
      13 to simvastatin (27.7 %); 12 to fluvastatin (25.5 %); 4 to lovastatin (8.5 %)
      and 2 to pravastatin (4.3 %). Statins represented approximately half of the
      cardiovascular group which occupied 3rd place (10 %), after anti-infectious
      agents (37 %) and central nervous system drugs (14 %). The hepatocellular pattern
      was predominant, especially in the simvastatin group (85%), the cholestatic/mixed
      pattern was more frequent with fluvastatin (66 %) and had a similar distribution
      to atorvastatin. Patients with statin-induced toxicity were older (62 years
      versus 53 years, p < 0.001) and more often demonstrated anautoimmune hepatitis
      phenotype (8.5 % versus 1.4 %, p < 0.003). CONCLUSIONS: Statins are not a common
      cause of hepatotoxicity in Spain. Atorvastatin is the statin involved in the
      greatest number of incidents. The liver injury pattern varies among the different
      statins. The hepatitis phenotype with autoimmune features appears to be a
      characteristic signature of statin-induced hepatotoxicity.

PMID- 25075656
TI  - The effect of glutamine and synbiotics on the healing of colonic anastomosis.
AB  - INTRODUCTION: Intestinal wound healing is an essential process for surgical
      reconstruction of the digestive tract. The purpose of this study is to evaluate
      the effect of perioperative administration of glutamine and synbiotics on the
      biological behavior of intestinal mucosal barrier and the healing of colonic
      anastomosis in rats. MATERIAL AND METHODS: 80 Wistar rats were divided in five
      groups. A: Control. B: Mechanical bowel preparation and antibiotics.C: Glutamine.
      D: Synbiotics. E: Glutamine and synbiotics. The animals were sacrificed on 3rd
      and 7th postoperative day. RESULTS: Zero mortality and no septic complications
      were noted. On 3rd postoperative days, a significant weight loss was observed in
      all groups in comparison with the preoperative weights, but on the 7th day in
      groups C and E, in contrast with the other groups, weight loss was not
      significant. On the 3rd postoperative day, neoangiogenesis, inflammatory
      infiltration and fibroblast activity were significantly enhanced in group E
      compared to control. On the 7th postoperative day in group E fibroblast activity
      was significantly enhanced and inflammatory infiltration was significantly
      limited compared to control. The bursting pressures as well as the hydroxyproline
      tissue content were significantly higher in the group E on 3rd and 7th
      postoperative days. The percentage of positive mesenteric lymph node cultures
      were significantly limited in group E compared to control. CONCLUSIONS: The
      administration of synbiotics in conjunction with glutamine resulted in increasing
      the mechanical strength of the anastomosis, thus increasing the bursting pressure
      and decreasing or effacing of anastomotic dehiscence and limiting bacterial
      translocation.

PMID- 25075657
TI  - Polycystic liver in the adult (PLA) in Spain: analysis of a structured survey
      analyzing the experience and attitude of gastroenterologists in Spain.
AB  - BACKGROUND: Polycystic liver in the adult (PLA) is a rare disease characterized
      by chronic liver enlargement. OBJECTIVE: To analyse gastroenterologists'
      involvement in, experience with, and attitude toward diagnosing, monitoring,
      andtreating patients with PLA in Spain. METHODS: Each of seven study coordinators
      contacted 15 specialists in their geographic area about participating in the
      study via an online structured survey. RESULTS: Of the 105 clinics contacted, 88
      completed the questionnaire, with a mean of 3 patients being followed per
      practice, although 6 clinics were following more than 20 patients with PLA.
      Patients were being followed mainly by the Department of Hepatology (81 %) and/or
      the Department of Gastroenterology (33 %). The majority of patients were
      diagnosed (98 %) and monitored (97 %) using liver ultrasound. When diagnosed, 76
      % of patients were under 50 years of age, females predominating.The primary
      treatment objective for the patients was symptomatic management. Pharmacotherapy
      was prescribed by 28 % of physicians: Somatostatin analogues, primarily, followed
      by mTOR inhibitors. One-third of the clinics indicated that they had patients who
      had undergone liver transplant and/or surgery. CONCLUSIONS: Ultrasound is the
      diagnosing and monitoring method of choice. Among the clinics using
      pharmacotherapy for symptomatic management, somatostatin analogues were the drugs
      of choice. These clinics' infrequent use of invasive procedures suggests that
      they perceive the various invasive techniques as not very effective.

PMID- 25075658
TI  - Genetic and molecular mechanisms leading to eosinophilic esophagitis.
AB  - From the epidemiologic studies, to the first genome wide association study in
      2010, the understanding of the molecular pathogenesis of EoE has been both
      inspiring and puzzling. Epidemiologic studies have highlighted the contribution
      of the genetic in the EoE disease by emphasizing the presence of familial type of
      EoE, but has also revealed the complexity of its transmission that does not
      follow a Mendelian inheritance. The molecular pathogenesis advances have helped
      in the understanding of the mechanisms underlying this esophageal inflammation
      but has also allow the identification of candidate genes for which single
      nucleotide polymorphisms (SNP) are associated with the disease. Recently, the
      genome wide analysis of more than half a million single nucleotide polymorphism
      has allowed the identification of gene variations associated with the EoE disease
      and has led to substantial advance in the understanding of the molecular
      mechanisms leading to EoE. Undeniably, EoE is a complex polygenic disease and we
      certainly are only at the ground level of its detailed comprehension.

PMID- 25075659
TI  - Anorectal melanoma associated with colonic metastasis.

PMID- 25075660
TI  - Bouveret's syndrome: evaluation with multidetector CT.

PMID- 25075661
TI  - Peri-ileostomy pyoderma gangrenosum. Case report.
AB  - Pyoderma gangrenosum is one of the most severe complications that can occur
      following stoma placement. Despite few cases reported in the literature, it is
      considered an underdiagnosed entity. We present a case of peri-ileostomy pyoderma
      gangrenosum (PPG) in a patient who underwent a pancoloproctectomy and permanent
      ileostomy due to ulcerative colitis (UC). Treatment was based on local cures,
      proper fitting of ostomy devices, topical tacrolimus and systemic
      corticosteroids, adalimumab and antibiotics. Satisfactory resolution was achieved
      in eight weeks. 

PMID- 25075662
TI  - Nodular regenerative hyperplasia of the liver and cutaneous T-cell lymphoma: an
      unreported association.
AB  - Nodular regenerative hyperplasia of the liver -a type of noncirrhotic portal
      hypertension- is a rare condition of unknown etiopathogenesis that has been
      associated with multiple disorders, including diverse types of hematologic
      disease. We report the case of a 36-year-old female patient diagnosed with
      cutaneous T-cell lymphoma of the mycosis fungoides variety, staged as T2N0M0B0,
      where a transjugular liver biopsy demonstrated the presence of nodular
      regenerative hyperplasia with a hepatic venous pressure gradient of 15 mm Hg. The
      study was triggered by the incidental radiologic finding of hepatomegaly with
      indirect evidence of portal hypertension. We are not aware of any previous
      reports on the association of nodular regenerative hyperplasia with mycosis
      fungoides in the medical literature. 

PMID- 25075663
TI  - [Pain in the abdominal wall].

PMID- 25075664
TI  - Hypoxic hepatitis as diabetic ketoacidosis complication.

PMID- 25075666
TI  - Massive splenic infarction leading to sickle cell disease.

PMID- 25075665
TI  - The effect of controlling inflammatory activity in the colon on the response to
      infliximab of autoimmune haemolytic anaemia associated with ulcerative colitis.

PMID- 25075667
TI  - A rare case of giant pseudopolyp and colitis cystica profunda coexistence in an
      ulcerative colitis patient.

PMID- 25075668
TI  - Ileal carcinoid tumor within Crohn's disease.

PMID- 25075669
TI  - Why does bromine square palladium off? An ab initio study of brominated palladium
      and its nanomorphology.
AB  - A first-principles description and prediction of brominated nanocrystals of Pd is
      presented. In particular, we conducted an extensive study of the adsorption
      behaviour of Br on various Pd surfaces (including both low and high Miller-index
      surfaces) as a function of its surface coverage. By coupling our calculated
      surface energies with ab initio (electrochemical) thermodynamics and the Gibbs
      Wulff shape model, we find that the relative stability of the Pd surfaces is
      strongly modified by Br, allowing high Miller-index surfaces of Pd (namely the
      (210) surface) to become competitively favourable at moderate concentrations of
      Br. We also show that Pd nanoparticles assume a cube-like crystal shape at high
      concentrations of Br, exposing mainly the (100) facets with a Br surface coverage
      of 0.5 ML. This not only confirms and explains recent solution synthesis results,
      but also provides a quantitative atomic picture of the exposed surface facets,
      which is crucial in understanding the local surface chemistry of shape-controlled
      nanoparticles for better nanocatalyst design. 

PMID- 25075670
TI  - Monitoring the effectiveness of root canal procedures on endotoxin levels found
      in teeth with chronic apical periodontitis.
AB  - OBJECTIVE: The aim of this study was to monitor the effectiveness of root canal
      procedures by using different irrigants and intracanal medication on endotoxin
      levels found in root canals of teeth with chronic apical periodontitis. MATERIAL
      AND METHODS: Thirty root canals of teeth with pulpal necrosis associated with
      periapical lesions were selected and randomly divided into groups according to
      the irrigants used: GI - 2.5% NaOCl, GII - 2% chlorhexidine (CHX) gel, and GIII -
      saline solution (SS) (all, n=10). Samples were collected with sterile/apyrogenic
      paper points before (S1) and after root canal instrumentation (S2), after use of
      17% ethylenediaminetetraacetic acid (EDTA) (S3), and after 30 days of intracanal
      medication (Ca(OH)2+SS) (S4). A turbidimetric kinetic Limulus Amebocyte Lysate
      assay was used for endotoxin measurement. RESULTS: Endotoxins were detected in
      100% of the root canals investigated (30/30), with a median value of 18.70 EU/mL.
      After S2, significant median percentage reduction was observed in all groups,
      irrespective of the irrigant tested: 2.5% NaOCl (99.65%) (GI), 2% CHX (94.27%)
      (GII), and SS (96.79%) (GIII) (all p<0.05). Root canal rinse with 17% EDTA (S3)
      for a 3-minute period failed to decrease endotoxin levels in GI and a slight
      decrease was observed in GII (59%) and GIII (61.1%) (all p>0.05). Intracanal
      medication for 30 days was able to significantly reduce residual endotoxins: 2.5%
      NaOCl (90%) (GI), 2% CHX (88.8%) (GII), and SS (85.7%) (GIII, p<0.05). No
      differences were found in the endotoxin reduction when comparing s2 and s4
      treatment groups. CONCLUSION: Our findings demonstrated the effectiveness of the
      mechanical action of the instruments along with the flow and backflow of irrigant
      enduring root canal instrumentation for the endotoxin removal from root canals of
      teeth with chronic apical periodontitis. Moreover, the use of intracanal
      medication for 30 days contributed for an improvement of endotoxin reduction.

PMID- 25075671
TI  - Rat subcutaneous tissue response to calcium silicate containing different arsenic
      concentrations.
AB  - OBJECTIVE: To evaluate the response of rat subcutaneous tissue in implanted
      polyethylene tubes that were filled with GMTA Angelus and Portland cements
      containing different arsenic concentrations. MATERIAL AND METHODS: Atomic
      absorption spectrophotometry was utilized to obtain the values of the arsenic
      concentration in the materials. Thirty-six rats were divided into 3 groups of 12
      animals for each experimental period. Each animal received two implants of
      polyethylene tubes filled with different test cements and the lateral of the
      tubes was used as a control group. After 15, 30 and 60 days of implantation, the
      animals were killed and the specimens were prepared for descriptive and
      morphometric analysis considering: inflammatory cells, collagen fibers,
      fibroblasts, blood vessels and other components. The results were analyzed
      utilizing the Kuskal-Wallis test and the Dunn's Multiple test for comparison
      (p<0.05). RESULTS: The materials showed, according to atomic absorption
      spectrophotometry, the following doses of arsenic: GMTA Angelus: 5.01 mg/kg, WPC
      Irajazinho: 0.69 mg/kg, GPC Minetti: 18.46 mg/kg and GPC Votoran: 10.76 mg/kg. In
      a 60-day periods, all specimens displayed a neoformation of connective tissue
      with a structure of fibrocellular aspect (capsule). Control groups and MTA
      Angelus produced the lower amount of inflammatory reaction and GPC Minetti, the
      highest reaction. CONCLUSIONS: There was no direct relationship between the
      concentration of arsenic present in the composition of the materials and the
      intensity of the inflammatory reactions. Higher values, as 18.46 mg/kg of arsenic
      in the cement, produce characteristics of severe inflammation reaction at the 60
      day period. The best results were found in MTA angelus.

PMID- 25075672
TI  - Effect of coffee and a cola-based soft drink on the color stability of bleached
      bovine incisors considering the time elapsed after bleaching.
AB  - There is no consensus about the waiting time necessary for the patient to start
      consuming beverages containing colorants again after bleaching. OBJECTIVE: To
      evaluate the influence of beverages with coloring agents on bleached bovine
      incisors considering the time elapsed after bleaching. MATERIALS AND METHODS:
      Sixty bovine incisors were bleached with 35% hydrogen peroxide for in-office use
      (Whiteness HP Max) and divided into 10 groups. The color was evaluated with a
      spectrophotometer (Spectro Shade MICRO) before and after bleaching, employing the
      CIE-Lab system. After bleaching, the teeth were exposed for 5 min to coffee or
      cola-based soft drink (CBSD) at different periods after bleaching: 10 min, 1 h,
      24 h, 48 h, and 72 h. Color (?E) and lightness (?L) variations were obtained from
      the CIE-Lab coordinates. Data were subjected to two-way ANOVA and Tukey HSD tests
      (p<0.05). RESULTS: Significant differences were observed between groups for both
      the ?L and ?E values (p<0.001). All specimens presented a decrease in brightness
      (negative ?L). The highest ?E values were observed for teeth stained with a CBSD
      at 10 min and 1 h (4.12 and 4.16, respectively). Teeth pigmented with coffee
      presented ?E values below 3.3 units for all evaluation times. CONCLUSION: The
      exposure to coffee after bleaching causes less color changes than the exposure to
      a CBSD regardless of the time after bleaching.

PMID- 25075674
TI  - Getting to the heart of the matter.

PMID- 25075673
TI  - Mechanical properties of composites as functions of the syringe storage
      temperature and energy dose.
AB  - OBJECTIVE: To investigate the mechanical properties of different classifications
      of composites indicated for posterior application as functions of the storage
      condition and of the energy dose. MATERIAL AND METHODS: Specimens (8 x 2 x 2 mm)
      were obtained according to the factors: I) Composites (3M ESPE): Filtek P60,
      Filtek Z350XT, and Filtek Silorane; II) Syringe storage conditions: room
      temperature, aged, oven, refrigerator, and freezer; and III) Energy dose: 24
      J/cm(2) and 48 J/cm(2). After photoactivation, the specimens were stored at 37 oC
      for 24 h. After storage, a three-point bending test was carried out in a
      universal testing machine at 0.5 mm/min. Flexural strength (S) and flexural
      modulus (E) were calculated. Data were analyzed by three-way ANOVA and Tukey's
      test (alpha = 0.05). RESULTS: Different storage conditions significantly affected
      the silorane composite for S; conversely, no effects were noted in terms of E.
      The accelerated aging protocol significantly increased the S of Filtek P60 and
      Filtek Silorane, whereas storage in the oven significantly decreased the S for
      all of the composites tested. Filtek P60 was the only composite not affected by
      the lower storage temperatures tested for S, whereas for the silorane this
      parameter was impacted at the same conditions. The factor "dose" was not
      statistically significant. CONCLUSIONS: The syringe storage at different
      temperature conditions proved to influence mostly the flexural strength, a
      clinically important characteristic considering the posterior indication of the
      materials tested. The silorane composite should not be stored at lower
      temperatures.

PMID- 25075675
TI  - Mandatory ECG screening for young athletes.

PMID- 25075676
TI  - Domestic violence questions.

PMID- 25075677
TI  - Workplace fatigue.

PMID- 25075678
TI  - Hard of hearing.

PMID- 25075679
TI  - Teaching history.

PMID- 25075680
TI  - Positive leadership.

PMID- 25075683
TI  - A combination drug for HIV prevention in high-risk groups.

PMID- 25075684
TI  - Do Massachusetts health care reform outcomes presage ACA results?

PMID- 25075686
TI  - Cervical cancer incidence may be higher than previously thought.

PMID- 25075689
TI  - Pediatric ACL Injuries.
AB  - New recommendations focus on prevention, particularly in young girls. 

PMID- 25075691
TI  - Medical marijuana: a hazy state of affairs for nurses.

PMID- 25075695
TI  - Early vs. delayed removal of dressings covering surgical wounds.
AB  - Editor's note: This is a summary of a nursing care-related systematic review from
      the Cochrane Library. 

PMID- 25075699
TI  - Presenting and interpreting findings.
AB  - This article is the sixth and last in a series on the systematic review from the
      Joanna Briggs Institute, an international collaborative supporting evidence-based
      practice in nursing, medicine, and allied health fields. The purpose of the
      series is to describe how to conduct a systematic review-one step at a time. This
      article details what should be included when presenting the findings of a
      systematic review to ensure they can be translated into clinical practice. 

PMID- 25075704
TI  - Starting a job as adjunct clinical instructor.
AB  - This article is the second in a new quarterly series on the roles of adjunct
      clinical faculty and preceptors, who teach nursing students to apply knowledge in
      clinical settings. Topics will include the preparation of clinical instructors
      and preceptors for these roles, the student evaluation process, and overcoming
      challenges that can come with teaching in the clinical field and with adjunct
      teaching. 

PMID- 25075705
TI  - Using evidence-based practice to prevent hospital-acquired pressure ulcers and
      promote wound healing.
AB  - A hospital and a nursing education program collaborate to improve skin care. 

PMID- 25075706
TI  - Climate change and health.

PMID- 25075707
TI  - On the phone.

PMID- 25075709
TI  - The Seventh q-bio Conference: meeting report and preface.

PMID- 25075710
TI  - Aortic morphologic findings after thoracic endovascular aortic repair for type B
      aortic dissection.
AB  - IMPORTANCE: Thoracic endovascular aortic repair (TEVAR) is used in the treatment
      of type B aortic dissections. Information related to aortic morphologic findings
      and the condition of the abdominal aorta after TEVAR is limited. OBJECTIVE: To
      analyze aortic morphologic findings after TEVAR for type B aortic dissections.
      DESIGN, SETTING, AND PARTICIPANTS: After a retrospective database review, the
      data for 30 patients who underwent TEVAR from January 1, 2007, through December
      31, 2013, for type B aortic dissection were analyzed. Imaging software was used
      to calculate aortic diameters and volumes of the aorta on computed tomography
      (CT) or magnetic resonance imaging (MRI). Mean follow-up was 14.4 months.
      INTERVENTIONS: We performed TEVAR to cover proximal thoracic aorta tears in
      patients who underwent acute or chronic type B aortic dissections. MAIN OUTCOMES
      AND MEASURES: Aortic morphologic findings of pre-TEVAR CT or MRI were compared
      with the most recent findings of post-TEVAR CT or MRI. Frequency of thoracic
      false lumen thrombosis (FLT) and false lumen patency (FLP) was determined and the
      effect on post-TEVAR aortic morphologic findings analyzed. RESULTS: Mean (SD)
      TEVAR increased true lumen diameter (19.50 [6.92] mm to 31.19 [5.36] mm, P <
      .001) and volume (77.92 [41.70] mL to 166.95 [69.69] mL, P < .001) and decreased
      false lumen diameter (29.77 [12.55] mm to 21.92 [12.05] mm, P = .001) on post
      TEVAR CT or MRI when compared with pre-TEVAR scans. Seventy percent of patients
      experienced thoracic FLT; 30% had FLP. True lumen volume expansion and false
      lumen volume regression occurred in patients with FLT (82.07 [46.95] mm to 180.55
      [77.99] mm, P < .001 and 161.84 [106.36] mm to 115.76 [140.77] mm, P = .002,
      respectively) and FLP (68.23 [21.43] mm to 128.22 [21.46] mm, P < .001 and 238.64
      [174.00] mm to 198.93 [120.46] mm, P = .04, respectively). Patients with FLT had
      increased true lumen diameter (15.67 [6.43] mm to 26.13 [7.62] mm, P < .001) and
      volume (54.86 [30.52] mL to 88.08 [41.07] mL, P = .001) in the abdominal aorta
      after TEVAR, with no change in total abdominal aortic volume (161.94 [70.12] mL
      vs 160.36 [82.11] mL, P = .90). Total abdominal aortic volume significantly
      increased in patients with thoracic FLP (187.24 [89.88] mL to 221.41 [82.64] mL,
      P = .02). CONCLUSIONS AND RELEVANCE: Favorable aortic remodeling of the thoracic
      aorta occurs after TEVAR for type B aortic dissections in patients with thoracic
      FLT and FLP. However, failure to achieve thrombosis of the thoracic false lumen
      negatively influences aortic morphologic findings of the contiguous abdominal
      aorta.

PMID- 25075711
TI  - Cognition and motivation as treatment targets in schizophrenia.

PMID- 25075712
TI  - Primary tumor staging for oral cancer and a proposed modification incorporating
      depth of invasion: an international multicenter retrospective study.
AB  - IMPORTANCE: The current American Joint Committee on Cancer (AJCC) staging system
      for oral cancer demonstrates wide prognostic variability within each primary
      tumor stage and provides suboptimal staging and prognostic information for some
      patients. OBJECTIVE: To determine if a modified staging system for oral cancer
      that integrates depth of invasion (DOI) into the T categories improves prognostic
      performance compared with the current AJCC T staging. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective analysis of 3149 patients with oral squamous cell
      carcinoma treated with curative intent at 11 comprehensive cancer centers
      worldwide between 1990 and 2011 with surgery +/- adjuvant therapy, with a median
      follow-up of 40 months. MAIN OUTCOMES AND MEASURES: We assessed the impact of DOI
      on disease-specific and overall survival in multivariable Cox proportional hazard
      models and investigated for institutional heterogeneity using 2-stage random
      effects meta-analyses. Candidate staging systems were developed after
      identification of optimal DOI cutpoints within each AJCC T category using the
      Akaike information criterion (AIC) and likelihood ratio tests. Staging systems
      were evaluated using the Harrel concordance index (C-index), AIC, and visual
      inspection for stratification into distinct prognostic categories, with internal
      validation using bootstrapping techniques. RESULTS: The mean and median DOI were
      12.9 mm and 10.0 mm, respectively. On multivariable analysis, DOI was a
      significantly associated with disease-specific survival (P < .001), demonstrated
      no institutional prognostic heterogeneity (I2 = 6.3%; P = .38), and resulted in
      improved model fit compared with T category alone (lower AIC, P < .001). Optimal
      cutpoints of 5 mm in T1 and 10 mm in T2-4 category disease were used to develop a
      modified T staging system that was preferred to the AJCC system on the basis of
      lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement
      in bootstrapped C-index. CONCLUSIONS AND RELEVANCE: We propose an improved oral
      cancer T staging system based on incorporation of DOI that should be considered
      in future versions of the AJCC staging system after external validation.

PMID- 25075715
TI  - Personality domains and traits that predict self-reported aberrant driving
      behaviours in a southeastern US university sample.
AB  - Personality traits are meaningful predictors of many significant life outcomes,
      including mortality. Several studies have investigated the relationship between
      specific personality traits and driving behaviours, e.g., aggression and
      speeding, in an attempt to identify traits associated with elevated crash risk.
      These studies, while valuable, are limited in that they examine only a narrow
      range of personality constructs and thus do not necessarily reveal which traits
      in constellation best predict aberrant driving behaviours. The primary aim of
      this study was to use a comprehensive measure of personality to investigate which
      personality traits are most predictive of four types of aberrant driving
      behaviour (Aggressive Violations, Ordinary Violations, Errors, Lapses) as
      indicated by the Manchester Driver Behaviour Questionnaire (DBQ). We recruited
      285 young adults (67% female) from a university in the southeastern US. They
      completed self-report questionnaires including the DBQ and the Personality
      Inventory for DSM-5, which indexes 5 broad personality domains (Antagonism,
      Detachment, Disinhibition, Negative Affectivity, Psychoticism) and 25 specific
      trait facets. Confirmatory factor analysis showed adequate evidence for the DBQ
      internal structure. Structural regression analyses revealed that the personality
      domains of Antagonism and Negative Affectivity best predicted both Aggressive
      Violations and Ordinary Violations, whereas the best predictors of both Errors
      and Lapses were Negative Affectivity, Disinhibition and to a lesser extent
      Antagonism. A more nuanced analysis of trait facets revealed that Hostility was
      the best predictor of Aggressive Violations; Risk-taking and Hostility of
      Ordinary Violations; Irresponsibility, Separation Insecurity and Attention
      Seeking of Errors; and Perseveration and Irresponsibility of Lapses. 

PMID- 25075714
TI  - Short-term rapamycin treatment in mice has few effects on the transcriptome of
      white adipose tissue compared to dietary restriction.
AB  - Rapamycin, a drug that has been shown to increase lifespan in mice, inhibits the
      target of rapamycin (TOR) pathway, a major pathway that regulates cell growth and
      energy status. It has been hypothesized that rapamycin and dietary restriction
      (DR) extend lifespan through similar mechanisms/pathways. Using microarray
      analysis, we compared the transcriptome of white adipose tissue from mice fed
      rapamycin or DR-diet for 6 months. Multidimensional scaling and heatmap analyses
      showed that rapamycin had essentially no effect on the transcriptome as compared
      to DR. For example, only six transcripts were significantly altered by rapamycin
      while mice fed DR showed a significant change in over 1000 transcripts. Using
      ingenuity pathway analysis, we found that stearate biosynthesis and circadian
      rhythm signaling were significantly changed by DR. Our findings showing that DR,
      but not rapamycin, has an effect on the transcriptome of the adipose tissue,
      suggesting that these two manipulations increase lifespan through different
      mechanisms/pathways. 

PMID- 25075717
TI  - Nicotine, cotinine, and beta-nicotyrine inhibit NNK-induced DNA-strand break in
      the hepatic cell line HepaRG.
AB  - Recent in vitro work using purified enzymes demonstrated that nicotine and/or a
      nicotine metabolite could inhibit CYPs (CYP2A6, 2A13, 2E1) involved in the
      metabolism of the genotoxic tobacco nitrosamine NNK. This observation raises the
      possibility of nicotine interaction with the mechanism of NNK bioactivation.
      Therefore, we hypothesized that nicotine or a nicotine metabolite such as
      cotinine might contribute to the inhibition of NNK-induced DNA strand breaks by
      interfering with CYP enzymes. The effect of nicotine and cotinine on DNA strand
      breaks was evaluated using the COMET assay in CYP competent HepaRG cells
      incubated with bioactive CYP-dependent NNK and CYP-independent NNKOAc (4
      (acetoxymethylnitrosoamino)-1-(3-pyridyl)-1-butanone). We report a dose-dependent
      reduction in DNA damage in hepatic-derived cell lines in the presence of nicotine
      and cotinine. Those results are discussed in the context of the in vitro model
      selected.

PMID- 25075718
TI  - Adjuvant-active fraction from Albizia julibrissin saponins improves immune
      responses by inducing cytokine and chemokine at the site of injection.
AB  - The total saponin from the stem bark of Albizia julibrissin (AJSt) has previously
      showed the adjuvant potentials in mice. In this study, AJSt was subjected to
      resin column chromatography to afford four fractions (AJS30, AJS50, AJS75 and
      AJS95), and these fractions were further compared for the hemolytic activities
      and adjuvant potentials on the immune response to ovalbumin (OVA) and recombinant
      fowl pox virus vector-based avian influenza vaccine (rFPV). AJSt, AJS50, AJS75
      and AJS95 showed a slight hemolytic effect. AJSt, AJS50 and AJS75 significantly
      enhanced not only the concanavalin A (Con A)-, lipopolysaccharide (LPS)- and
      antigen-stimulated splenocyte proliferation, but also serum antigen-specific IgG,
      IgG1, IgG2a and IgG2b antibody titers in the mice immunized with OVA and rFPV.
      AJSt, AJS50 and AJS75 also significantly promoted the NK cell activity and
      delayed-type hypersensitivity (DTH) in the OVA-immunized mice. Furthermore, the
      mechanisms of adjuvant action were explored by determining the effects of AJS75
      on cytokines and chemokines at the site of injection using antibody array. AJS75
      induced or up-regulated the protein expression of 12 cytokines (IL-12p40, IL
      12p40/p70, IFN-gamma, IL-13, IL-1beta, IL-6, IL-10, TNF-alpha, sTNFR I, sTNFR
      III, IL-3 and IL-9) and 10 chemokines (Eotaxin, I-TAC, MIG, MIP-1alpha, RANTES,
      TECK, Fracatlkine, FasL, M-CSF and GM-CSF) in the injected muscles. The results
      suggested that AJS75, the most adjuvant-active fraction of AJSt, could improve
      antigen-specific both cellular and humoral immune responses and simultaneously
      elicit a Th1/Th2 response by inducing cytokine and chemokine at the site of
      injection. 

PMID- 25075716
TI  - FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia
      postmortem brains: basal contents and effects of psychotropic treatments.
AB  - Enhanced brain apoptosis (neurons and glia) may be involved in major depression
      (MD) and schizophrenia (SZ), mainly through the activation of the intrinsic
      (mitochondrial) apoptotic pathway. In the extrinsic death pathway, pro-apoptotic
      Fas-associated death domain (FADD) adaptor and its non-apoptotic p-Ser194 FADD
      form have critical roles interacting with other death regulators such as
      phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) and extracellular signal
      regulated kinase (ERK). The basal status of FADD (protein and messenger RNA
      (mRNA)) and the effects of psychotropic drugs (detected in blood/urine samples)
      were first assessed in postmortem prefrontal cortex of MD and SZ subjects
      (including a non-MD/SZ suicide group). In MD, p-FADD, but not total FADD (and
      mRNA), was increased (26%, n=24; all MD subjects) as well as p-FADD/FADD ratio (a
      pro-survival marker) in antidepressant-free MD subjects (50%, n=10). In contrast,
      cortical FADD (and mRNA), p-FADD, and p-FADD/FADD were not altered in SZ brains
      (n=21) regardless of antipsychotic medications (except enhanced mRNA in treated
      subjects). Similar negative results were quantified in the non-MD/SZ suicide
      group. In MD, the regulation of multifunctional PEA-15 (i.e., p-Ser116 PEA-15
      blocks pro-apoptotic FADD and PEA-15 prevents pro-survival ERK action) and the
      modulation of p-ERK1/2 were also investigated. Cortical p-PEA-15 was not changed
      whereas PEA-15 was increased mainly in antidepressant-treated subjects (16-20%).
      Interestingly, cortical p-ERK1/2/ERK1/2 ratio was reduced (33%) in antidepressant
      free when compared to antidepressant-treated MD subjects. The neurochemical
      adaptations of brain FADD (increased p-FADD and pro-survival p-FADD/FADD ratio),
      as well as its interaction with PEA-15, could play a major role to counteract the
      known activation of the mitochondrial apoptotic pathway in MD.

PMID- 25075719
TI  - Comparison of the bacterial community structure within the equine hindgut and
      faeces using Automated Ribosomal Intergenic Spacer Analysis (ARISA).
AB  - The horse's hindgut bacterial ecosystem has often been studied using faecal
      samples. However few studies compared both bacterial ecosystems and the validity
      of using faecal samples may be questionable. Hence, the present study aimed to
      compare the structure of the equine bacterial community in the hindgut (caecum,
      right ventral colon) and faeces using a fingerprint technique known as Automated
      Ribosomal Intergenic Spacer Analysis (ARISA). Two DNA extraction methods were
      also assessed. Intestinal contents and faeces were sampled 3 h after the morning
      meal on four adult fistulated horses fed meadow hay and pelleted concentrate.
      Irrespective of the intestinal segment, Principal Component Analysis of ARISA
      profiles showed a strong individual effect (P<0.0001). However, across the study,
      faecal bacterial community structure significantly (P<0.001) differed from those
      of the caecum and colon, while there was no difference between the two hindgut
      communities. The use of a QIAamp((r)) DNA Stool Mini kit increased the quality of
      DNA extracted irrespective of sample type. The differences observed between
      faecal and hindgut bacterial communities challenge the use of faeces as a
      representative for hindgut activity. Further investigations are necessary to
      compare bacterial activity between the hindgut and faeces in order to understand
      the validity of using faecal samples.

PMID- 25075720
TI  - Primary healthcare nurses' experiences of physical activity referrals: an
      interview study.
AB  - AIM: The aim of this study is to illuminate primary health care (PHC) nurses'
      experiences of physical activity referrals (PARs). BACKGROUND: Despite extensive
      knowledge about the substantial health effects physical activities can produce,
      fewer and fewer people in our modern society regularly engage in physical
      activity. Within health care and, particularly, within the PHC arena, nurses meet
      people on a daily basis who need help to engage in a healthier lifestyle. The
      possibility of issuing written prescriptions for physical activities, often
      referred to as PARs, has been introduced as a tool to support such lifestyles.
      However, even though PHC nurses can prescribe physical activities, studies
      investigating their experience in this type of nursing intervention are rare.
      METHODS: For this study, 12 semi-structured interviews were conducted with PHC
      nurses, and the transcribed texts were analysed using a qualitative content
      analysis. FINDINGS: Two categories--PARs, an important nursing intervention, and
      PARs, the necessity of organisational support--reflected the nurses' experiences
      in using PARs. CONCLUSION: Our findings suggest that viewing the PAR as a complex
      intervention, with all that this entails, might be one approach to increasing the
      number of PARs being issued. Simpler systems, more time and the potential for
      testing the effectiveness of follow-ups could be possible ways of achieving this.

PMID- 25075721
TI  - Quality of life and severity of skin and nail involvement in patients with plaque
      psoriasis.

PMID- 25075722
TI  - The hidden harms of using alcohol for pain relief in older adults.

PMID- 25075723
TI  - Development of a pilot project on data sharing among partners of the Italian Hub
      of Population Biobanks (HIBP): association between lipid profile and socio
      demographic variables.
AB  - The Italian Hub of Population Biobanks (HIBP) includes both ongoing and completed
      studies that are heterogeneous in both their purpose and in the specimens
      collected. The heterogeneity in starting conditions makes sharing study data very
      difficult because of technical, ethical, and collection rights issues that hamper
      collaboration and synergy. With the aim of overcoming these difficulties and
      establishing the "proof-of-concept" that sharing studies is achievable among
      Italian collections, a data-sharing pilot project has been agreed to by HIBP
      members. Participants agreed to the general methodology and signed a shared Data
      Transfer Agreement. The biobanks involved were: EURAC (Micros study), CIG (GEHA
      project), CNESPS (FINE, MATISS, MONICA, OEC1998, ITR (Italian Twin Register), and
      IPREA studies, and MOLIBANK (Moli-Sani project). Biobank data were uploaded into
      a common database using a dedicated informatics infrastructure. Demographic data,
      and anthropometric and hematochemical parameters were shared for each record.
      Each biobank uploaded into the common database a dataset with a minimum of 1000
      subjects, for a total of 5071 records. After a harmonization process, the final
      dataset included 3882 records. Subjects were grouped into three main geographic
      areas of Italy (North, Center, and South) and separate analyses were performed
      for men and women. The 3882 records were analyzed through multivariate logistic
      regression analysis. Results were expressed as odds ratios with 95% confidence
      interval. Results show several geographical differences in the lipidemic pattern,
      mostly regarding cholesterol-HDL, which represents a strong basis for further,
      deeper sample-based studies. This HIBP pilot study aimed to prove the feasibility
      of such collaborations and it provides a methodological prototype for future
      studies based on the participation in the partnership of well-established quality
      collections. 

PMID- 25075724
TI  - Subcutaneous fat necrosis of the newborn associated with hypercalcemia after
      therapeutic hypothermia.
AB  - Subcutaneous fat necrosis of the newborn (SCFN) is a rare, benign, and self
      limiting panniculitis of neonates that presents in the first few weeks of life
      and is most commonly associated with birth asphyxia and meconium aspiration.
      There have been few case reports of SCFN following therapeutic hypothermia. With
      the increasing use of therapeutic whole-body hypothermia, SCFN may become more
      prevalent. The differential diagnosis of SCFN can be broad, and clinicopathologic
      correlation is essential to make the correct and timely diagnosis. Clinicians
      should be aware of this rare disease and its potential serious complication
      hypercalcemia. 

PMID- 25075725
TI  - Juvenile ossifying fibroma of the middle turbinate.
AB  - Juvenile ossifying fibroma is a rare, benign tumor that may present in the
      sinonasal area but has never been described arising from the middle turbinate.
      The lesion's locally aggressive behavior and close proximity to orbit and
      anterior skull base create a significant challenge for the patient and
      practitioner. This is a case presentation of a 7-year-old female with an invasive
      recurrent juvenile ossifying fibroma arising from the middle turbinate. 

PMID- 25075726
TI  - Emerging causes of superficial and invasive infections following marine injuries
      and exposures.
AB  - Soft tissue bacterial infections following aquatic animal bites, stings, and
      minor injuries occur commonly and usually on the extremities in fishermen and
      beachgoers worldwide after freshwater and saltwater exposures. Louisiana has more
      tidal, saltwater, and brackish water shorelines (more than 7,000 miles) than any
      other state, including Alaska and Hawaii. As a result, Louisiana residents are
      often exposed to marine pathogens when fishing or working offshore or when
      enjoying Louisiana's miles of shorelines. Although many species of bacteria have
      been isolated from marine wounds, superficial soft tissue and invasive infections
      following marine injuries and exposures are most commonly caused by a small
      number of bacterial species, including Aeromonas hydrophila, Edwardsiella tarda,
      Erysipelothrix rhusiopathiae, Mycobacterium marinum, and Vibrio vulnificus. In
      addition to these species, several other aquatic bacteria have recently been
      identified as emerging causes of superficial and invasive infections following
      marine injuries and exposures, including marine mammal (dolphins and seals)
      Brucella species, Chromobacterium violaceum, Comamonas species, Shewanella algae,
      and Streptococcus iniae. The objectives of this review are to describe the
      epidemiology, presenting clinical manifestations, diagnostic and treatment
      strategies, and outcomes of both the superficial and the deeper invasive
      infections caused by the newly emerging marine bacterial pathogens. 

PMID- 25075727
TI  - The Association Between the Medical Home and Pediatric Developmental Screening
      Among US Children Five Years and Younger: Results From the 2007 National Survey
      of Children's Health.
AB  - OBJECTIVES: The medical home is associated with key healthcare services. We
      assessed its association with the pediatric developmental screening among United
      States (US) children less than or equal to five years. METHODS: The 2007 national
      survey of children's health data was analyzed using state clusters, and pediatric
      developmental screening probability was modeled as a function of the medical
      home. RESULTS: Only 19.5% of US children received pediatric developmental
      screening, and crosstabs showed a null medical home association. Based on medical
      home status, adjusted state models showed much variation in pediatric
      developmental screening odds. A random intercept and slope model had the best
      fit. The medical home increased pediatric developmental screening odds by 24%
      (1.10, 1.38). CONCLUSIONS: The pediatric developmental screening rate and the
      medical home association are partially influenced by an individual's state. A
      multilevel model including state level predictors will help illuminate factors
      that promote healthcare service acquisition. This knowledge will enhance policy
      development in public and private sector health programs.

PMID- 25075728
TI  - Hounsfield unit changes over time in contusions of the brain.
AB  - In the United States, traumatic brain injuries are an important cause of death
      and disability, often with significant financial and legal consequences. Although
      it is generally accepted by neuroradiologists that the density of cerebral
      contusions decreases over time, previous research has not addressed this
      phenomenon directly. In the current study, we reviewed charts of patients who had
      suffered cerebral contusions and had at least two subsequent computed tomography
      scans in order to determine whether Hounsfield Units, a measure of density,
      decreased over time. We found that 100% of contusions decreased in Hounsfield
      Units over time. In addition, we found that the rate of decrease in density
      appears to be higher in the first 100 days after the injury. These findings are
      especially applicable in the area of forensics. For example, they could be used
      to determine the relative age of two separate brain contusions in the same
      patient. 

PMID- 25075729
TI  - LSUHSC Department of Medicine White Coat Ceremony Address, 2014.

PMID- 25075730
TI  - ECG in a 52-Year-Old Man With a Dilated Cardiomyapathy. Atrial tachycardia
      (214/min) with atrioventricular (AV) block and complete AV dissociation from
      junctional tachycardia (140/min), together with repolarization changes of
      digitalis, suggest digitalis toxicity.

PMID- 25075731
TI  - Radiology case of the month: recurrent knee pain in a young athlete.
AB  - A 22-year-old male collegiate basketball player with a history of right knee pain
      presents with pain and swelling of his right knee. Physical exam reveals local
      swelling and tenderness over the right proximal tibial-fibular joint.

PMID- 25075732
TI  - Clinical case of the month: a 44-year-old woman with jaundice and abdominal pain.

PMID- 25075733
TI  - Pathology Image of the Month: Black Thyroid.
AB  - A 54-year-old Caucasian male had a witnessed collapse on the street. He was
      transported to the emergency department and subsequently pronounced dead. An
      unlimited autopsy examination was conducted under authorization of the coroner.
      Medical record review later revealed that the decedent had a history of alcohol
      abuse, chronic obstructive pulmonary disease, congestive heart failure, and
      chronic osteomyelitis treated by minocycline 100 mg twice daily. Autopsy revealed
      the cause of death to be ruptured gastroesophageal varices with nearly one liter
      of recent hemorrhage in the stomach and gastrointestinal tract. Other findings
      compatible with a history of alcoholism included hepatosplenomegaly, hepatic
      steatosis, and early bridging fibrosis. The decedent's thyroid was multinodular
      and enlarged at 50 gm. The thyroid gland, in its entirety, is shown below with
      serial sections made longitudinally through the gland capsule to reveal the
      underlying parenchyma. 

PMID- 25075734
TI  - Prescription opioid abuse: a literature review of the clinical and economic
      burden in the United States.
AB  - Between 2002 and 2007, the nonmedical use of prescription pain relievers grew
      from 11.0 million to 12.5 million people in the United States. Societal costs
      attributable to prescription opioid abuse were estimated at $55.7 billion in
      2007. The purpose of this study was to comprehensively review the recent clinical
      and economic evaluations of prescription opioid abuse. A comprehensive literature
      search was conducted for studies published from 2002 to 2012. Articles were
      included if they were original research studies in English that reported the
      clinical and economic burden associated with prescription opioid abuse. A total
      of 23 studies (183 unique citations identified, 54 articles subjected to full
      text review) were included in this review and analysis. Findings from the review
      demonstrated that rates of opioid overdose-related deaths ranged from 5528 deaths
      in 2002 to 14,800 in 2008. Furthermore, overdose reportedly results in 830,652
      years of potential life lost before age 65. Opioid abusers were generally more
      likely to utilize medical services, such as emergency department, physician
      outpatient visits, and inpatient hospital stays, relative to non-abusers. When
      compared to a matched control group (non-abusers), mean annual excess health care
      costs for opioid abusers with private insurance ranged from $14,054 to $20,546.
      Similarly, the mean annual excess health care costs for opioid abusers with
      Medicaid ranged from $5874 to $15,183. The issue of opioid abuse has significant
      clinical and economic consequences for patients, health care providers,
      commercial and government payers, and society as a whole.

PMID- 25075735
TI  - Gene chip/PCR-array analysis of tissue response to 2-methacryloyloxyethyl
      phosphorylcholine (MPC) polymer surfaces in a mouse subcutaneous transplantation
      system.
AB  - To evaluate the in vivo foreign body reaction to bio-inert 2-methacryloyloxyethyl
      phosphorylcholine (MPC) polymers, MPC polymer-coated porous substrates, with
      large surface area, were implanted subcutaneously in mice for 7 and 28 days, and
      the surrounding tissue response and cells infiltrating into the porous structure
      were evaluated. The MPC polymer surface induced low angiogenesis and thin
      encapsulation around the porous substrate, and slightly suppressed cell
      infiltration into the porous substrate. M1-type macrophage specific gene (CCR7)
      expression was suppressed by the MPC polymer surface after 7 days, resulting in
      the suppression of inflammatory cytokine/chemokine gene expression. However, the
      expression of these genes on the MPC polymer surface was higher than on the non
      coated surface after 28 days. These findings suggest that MPC polymer surfaces
      successfully inhibit inflammatory responses during the early stage of tissue
      response, and seem to retard its occurrence over time. 

PMID- 25075736
TI  - The Roles of Lysosomes in Inflammation and Autoimmune Diseases.
AB  - Lysosomes perform a range of functions, some of which, such as degradation, are
      common to all cell types. Others, such as secretion or lysosomal exocytosis, are
      more specialised and tend to involve fusion of this organelle with the cell
      surface to release its contents. This review describes lysosomal regulation of
      the inflammatory glucocorticoid signaling pathways, and summarizes the roles of
      lysosomes in negatively or positively modulating the production of inflammatory
      cytokines. We also review the characteristic changes in lysosomal hydrolases and
      membrane proteins in common autoimmune diseases. Finally, future directions in
      lysosome research are proposed, with it being suggested that the role of
      lysosomes will continue to be of growing interest in immunity research. 

PMID- 25075737
TI  - Experiences of coexisting with chronic illnesses among elderly women in
      communities.
AB  - Based on the increasing numbers of women in the aging population, the health of
      women will become critical in the future. Our purpose in this study was to
      analyze the experiences of elderly women with chronic illness. Twelve elderly
      Taiwanese women participated in in-depth interviews. "Using my own power out of
      the disease shackle" was the core category referring to elderly women who coexist
      with chronic illnesses. Elderly women should be provided with individually
      targeted plans for disease management and health maintenance to enable them to
      participate in health care decisions at the onset of chronic diseases. 

PMID- 25075739
TI  - Local-scale diversity and between-year "frozen evolution" of avian influenza A
      viruses in nature.
AB  - Influenza A virus (IAV) in wild bird reservoir hosts is characterized by the
      perpetuation in a plethora of subtype and genotype constellations. Multiyear
      monitoring studies carried out during the last two decades worldwide have
      provided a large body of knowledge regarding the ecology of IAV in wild birds.
      Nevertheless, other issues of avian IAV evolution have not been fully elucidated,
      such as the complexity and dynamics of genetic interactions between the co
      circulating IAV genomes taking place at a local-scale level or the phenomenon of
      frozen evolution. We investigated the IAV diversity in a mallard population
      residing in a single pond in the Czech Republic. Despite the relative small
      number of samples collected, remarkable heterogeneity was revealed with four
      different IAV subtype combinations, H6N2, H6N9, H11N2, and H11N9, and six genomic
      constellations in co-circulation. Moreover, the H6, H11, and N2 segments belonged
      to two distinguishable sub-lineages. A reconstruction of the pattern of genetic
      reassortment revealed direct parent-progeny relationships between the H6N2, H11N9
      and H6N9 viruses. Interestingly the IAV, with the H6N9 subtype, was re-detected a
      year later in a genetically unchanged form in the close proximity of the original
      sampling locality. The almost absolute nucleotide sequence identity of all the
      respective genomic segments between the two H6N9 viruses indicates frozen
      evolution as a result of prolonged conservation in the environment. The
      persistence of the H6N9 IAV in various abiotic and biotic environmental
      components was also discussed.

PMID- 25075740
TI  - Mechanochemical phosphorylation and solubilisation of beta-D-glucan from yeast
      Saccharomyces cerevisiae and its biological activities.
AB  - To obtain a water-soluble beta-D-glucan derivative cleanly and conveniently, a
      highly efficient mechanochemical method, planetary ball milling, was used to
      phosphorylate beta-D-glucan isolated from yeast Saccharomyces cerevisiae in solid
      state. Soluble beta-D-glucan phosphate (GP) with a high degree of substitution
      (0.77-2.09) and an apparent PEAK molecular weight of 6.6-10.0 kDa was produced
      when beta-D-glucan was co-milled with sodium hexametaphosphate at 139.5-186.0
      rad/s for 12-20 min. The energy transferred was 3.03-11.98 KJ/g. The
      phosphorylation of GPs was demonstrated by Fourier transform infrared
      spectroscopy and 13C and 31P Nuclear magnetic resonance spectroscopy. Three GP
      products with different degree of substitution (DS) and degree of polymerisation
      (DP) were able to upregulate the functional events mediated by activated murine
      macrophage RAW264.7 cells, among which GP-2 with a DS of 1.24 and DP of 30.5
      exerted the highest immunostimulating activity. Our results indicate that
      mechanochemical processing is an efficient method for preparing water-soluble and
      biologically active GP with high DS. 

PMID- 25075741
TI  - Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a
      cross-sectional observational study in patients with multiple sclerosis.
AB  - OBJECTIVES: Dendritic cells (DCs) serve a critical role both in promoting and
      inhibiting adaptive immunity. The goal of this study was to investigate the
      effect of natalizumab (NTZ) treatment on DC numbers, phenotype, and function in
      patients with multiple sclerosis (MS). METHODS: Frequency and phenotype of
      myeloid and plasmacytoid DCs (MDCs and PDCs, respectively) were analyzed in blood
      from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS
      patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides
      or co-cultured with homologous T cells in the presence or absence of NTZ in vitro
      to determine functional effects of NTZ treatment. RESULTS: We observed that NTZ
      treatment was associated with a 25-50% reduction in PDC frequency in peripheral
      blood as compared to untreated MS patients, while the frequency of MDCs was
      unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype
      with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in
      vitro treatment with NTZ did not increase markers of PDC activation or their
      ability to induce T cell differentiation. CONCLUSION: Our study shows that NTZ
      treatment is associated with a reduced frequency of PDCs in the peripheral
      circulation, but that PDCs in NTZ-treated individuals display an activated
      phenotype. Taken together the data suggests that transmigration of activated PDCs
      is preferentially affected by blockade of integrin alpha4 leading to an increased
      frequency of activated PDCs in blood.

PMID- 25075742
TI  - The association between quality of HIV care, loss to follow-up and mortality in
      pediatric and adolescent patients receiving antiretroviral therapy in Nigeria.
AB  - Access to pediatric HIV treatment in resource-limited settings has risen
      significantly. However, little is known about the quality of care that pediatric
      or adolescent patients receive. The objective of this study is to explore quality
      of HIV care and treatment in Nigeria and to determine the association between
      quality of care, loss-to-follow-up and mortality. A retrospective cohort study
      was conducted including patients <=18 years of age who initiated ART between
      November 2002 and December 2011 at 23 sites across 10 states. 1,516 patients were
      included. A quality score comprised of 6 process indicators was calculated for
      each patient. More than half of patients (55.5%) were found to have a high
      quality score, using the median score as the cut-off. Most patients were screened
      for tuberculosis at entry into care (81.3%), had adherence measurement and
      counseling at their last visit (88.7% and 89.7% respectively), and were
      prescribed co-trimoxazole at some point during enrollment in care (98.8%). Thirty
      seven percent received a CD4 count in the six months prior to chart review.
      Mortality within 90 days of ART initiation was 1.9%. A total of 4.2% of patients
      died during the period of follow-up (mean: 27 months) with 19.0% lost to follow
      up. In multivariate regression analyses, weight for age z-score (Adjusted Hazard
      Ratio (AHR): 0.90; 95% CI: 0.85, 0.95) and high quality indicator score (compared
      a low score, AHR: 0.43; 95% CI: 0.26, 0.73) had a protective effect on mortality.
      Patients with a high quality score were less likely to be lost to follow-up
      (Adjusted Odds Ratio (AOR): 0.42; 95% CI: 0.32, 0.56), compared to those with low
      score. These findings indicate that providing high quality care to children and
      adolescents living with HIV is important to improve outcomes, including lowering
      loss to follow-up and decreasing mortality in this age group.

PMID- 25075743
TI  - Characteristics and outcomes among older HIV-positive adults enrolled in HIV
      programs in four sub-Saharan African countries.
AB  - BACKGROUND: Limited information exists on adults >=50 years receiving HIV care in
      sub-Saharan Africa. METHODOLOGY: Using routinely-collected longitudinal patient
      level data among 391,111 adults >=15 years enrolling in HIV care from January
      2005-December 2010 and 184,689 initiating ART, we compared characteristics and
      outcomes between older (>=50 years) and younger adults at 199 clinics in Kenya,
      Mozambique, Rwanda, and Tanzania. We calculated proportions over time of newly
      enrolled and active adults receiving HIV care and initiating ART who were >=50
      years; cumulative incidence of loss to follow-up (LTF) and recorded death one
      year after enrollment and ART initiation, and CD4+ response following ART
      initiation. FINDINGS: From 2005-2010, the percentage of adults >=50 years newly
      enrolled in HIV care remained stable at 10%, while the percentage of adults >=50
      years newly initiating ART (10% [2005]-12% [2010]), active in follow-up (10%
      [2005]-14% (2010]), and active on ART (10% [2005]-16% [2010]) significantly
      increased. One year after enrollment, older patients had significantly lower
      incidence of LTF (33.1% vs. 32.6%[40-49 years], 40.5%[25-39 years], and 56.3%[15
      24 years]; p-value<0.0001), but significantly higher incidence of recorded death
      (6.0% vs. 5.0% [40-49 years], 4.1% [25-39 years], and 2.8% [15-24 years]; p
      valve<0.0001). LTF was lower after vs. before ART initiation for all ages, with
      older adults experiencing less LTF than younger adults. Among 85,763 ART patients
      with baseline and follow-up CD4+ counts, adjusted average 12-month CD4+ response
      for older adults was 20.6 cells/mm3 lower than for adults 25-39 years of age (95%
      CI: 17.1-24.1). CONCLUSIONS: The proportion of patients who are >=50 years has
      increased over time and been driven by aging of the existing patient population.
      Older patients experienced less LTF, higher recorded mortality and less robust
      CD4+ response after ART initiation. Increased programmatic attention on older
      adults receiving HIV care in sub-Saharan Africa is warranted.

PMID- 25075745
TI  - Deep-sea octopus (Graneledone boreopacifica) conducts the longest-known egg
      brooding period of any animal.
AB  - Octopuses typically have a single reproductive period and then they die
      (semelparity). Once a clutch of fertilized eggs has been produced, the female
      protects and tends them until they hatch. In most shallow-water species this
      period of parental care can last from 1 to 3 months, but very little is known
      about the brooding of deep-living species. In the cold, dark waters of the deep
      ocean, metabolic processes are often slower than their counterparts at shallower
      depths. Extrapolations from data on shallow-water octopus species suggest that
      lower temperatures would prolong embryonic development periods. Likewise,
      laboratory studies have linked lower temperatures to longer brooding periods in
      cephalopods, but direct evidence has not been available. We found an opportunity
      to directly measure the brooding period of the deep-sea octopus Graneledone
      boreopacifica, in its natural habitat. At 53 months, it is by far the longest egg
      brooding period ever reported for any animal species. These surprising results
      emphasize the selective value of prolonged embryonic development in order to
      produce competitive hatchlings. They also extend the known boundaries of
      physiological adaptations for life in the deep sea. 

PMID- 25075747
TI  - Eclipse prediction on the ancient Greek astronomical calculating machine known as
      the Antikythera Mechanism.
AB  - The ancient Greek astronomical calculating machine, known as the Antikythera
      Mechanism, predicted eclipses, based on the 223-lunar month Saros cycle. Eclipses
      are indicated on a four-turn spiral Saros Dial by glyphs, which describe type and
      time of eclipse and include alphabetical index letters, referring to solar
      eclipse inscriptions. These include Index Letter Groups, describing shared
      eclipse characteristics. The grouping and ordering of the index letters, the
      organization of the inscriptions and the eclipse times have previously been
      unsolved. A new reading and interpretation of data from the back plate of the
      Antikythera Mechanism, including the glyphs, the index letters and the eclipse
      inscriptions, has resulted in substantial changes to previously published work.
      Based on these new readings, two arithmetical models are presented here that
      explain the complete eclipse prediction scheme. The first model solves the glyph
      distribution, the grouping and anomalous ordering of the index letters and the
      structure of the inscriptions. It also implies the existence of lost lunar
      eclipse inscriptions. The second model closely matches the glyph times and
      explains the four-turn spiral of the Saros Dial. Together, these models imply a
      surprisingly early epoch for the Antikythera Mechanism. The ancient Greeks built
      a machine that can predict, for many years ahead, not only eclipses but also a
      remarkable array of their characteristics, such as directions of obscuration,
      magnitude, colour, angular diameter of the Moon, relationship with the Moon's
      node and eclipse time. It was not entirely accurate, but it was an astonishing
      achievement for its era. 

PMID- 25075746
TI  - Methodological aspects of ELISA analysis of thioredoxin 1 in human plasma and
      cerebrospinal fluid.
AB  - Thioredoxin-1 (Trx1) is a protein antioxidant involved in major cellular
      processes. Increased plasma levels of Trx1 have been associated with human
      diseases suggesting that Trx1 is a marker for oxidative stress with putative
      clinical use. However, the reported mean levels of Trx1 in the control cohorts
      vary a hundred-fold between studies (0.8-87 ng/ml), possibly due to
      methodological differences between the capture ELISA used in the different
      studies. The aim of this study was to investigate methodological aspects related
      to the ELISA measurement of Trx1. ELISAs utilizing different capture and
      detection combinations of antibodies to Trx1 and as well as recombinant human
      (rh) Trx1 standards from two sources were characterized. The different ELISAs
      were subsequently used to measure Trx1 in human plasma and cerebrospinal fluid
      samples (CSF) from healthy donors and from patients with various neurological
      diagnoses. The Trx1 standards differed in their content of monomeric and
      oligomeric Trx1, which affected the ELISAs composed of different antibody
      combinations. Thus, the levels of Trx1 determined in human plasma and CSF samples
      varied depending on the antibody used in the ELISAs and on the rhTrx1 standard.
      Furthermore, the relevance of preventing interference by heterophilic antibodies
      (HA) in human plasma and CSF was investigated. The addition of a HA blocking
      buffer to human samples drastically reduced the ELISA signals in many samples
      showing that HA are likely to cause false positive results unless they are
      blocked. In conclusion, the study shows that the design of a Trx1 ELISA in
      regards to antibodies and standards used has an impact on the measured Trx1
      levels. Importantly, analyses of human plasma and CSF without preventing HA
      interference may obscure the obtained data. Overall, the results of this study
      are crucial for the improvement of future studies on the association of Trx1
      levels with various diseases. 

PMID- 25075748
TI  - A case of galactosialidosis with novel mutations of the protective
      protein/cathepsin a gene: diagnosis prompted by trophoblast vacuolization on
      placental examination.
AB  - Galactosialidosis (GS) is a rare autosomal recessive lysosomal storage disease
      caused by a combined deficiency of lysosomal beta-galactosidase and neuraminidase
      as a result of a genetic defect in the protective protein/cathepsin A gene. We
      report a case of unsuspected fetal galactosialidosis presenting as severe
      intrauterine growth restriction and oligohydramnios prenatally and as
      hyperinsulinemic hypoglycemia in the immediate postnatal period. Placental
      pathology examination showed striking vacuolations of the villous
      syncytiotrophoblast, extravillous trophoblast, and villous Hofbauer cells.
      Electron microscopy revealed numerous membrane-bound electron-lucent lysosomes,
      mainly within the syncytiotrophoblast. The characteristic histologic and
      ultrastructural placental findings prompted biochemical and molecular genetic
      testing for fetal storage disease. Enzyme activity of beta-galactosidase was
      decreased in leukocytes and fibroblasts. Sialic acid content was elevated.
      Molecular genetic studies revealed 3 variants--c.108, 110delGCT(L37del),
      c.1045T>A (C349S), and c.1321C>T(R441C)--of the cathepsin A gene, the latter 2 of
      which have not been previously reported. These findings are consistent with
      galactosialidosis. We emphasize the importance of following the accepted practice
      guideline for the examination of the placenta in discovering unsuspected fetal
      metabolic disorders.

PMID- 25075749
TI  - Synthesis and biological evaluation of ( - )-13,14-dihydroxy-8,11,13
      podocarpatrien-7-one and derivatives from (+)-manool.
AB  - 13,14-Dihydroxy-8,11,13-podocarpatrien-7-one (1) and a series of ring C aromatic
      diterpene derivatives were synthesised from (+)-manool (4) and evaluated for
      their cytotoxic, leishmanicidal and trypanocidal activities. Our results
      indicated that compound 1 and other podocarpane-type intermediates are cytotoxic.
      Cleavage of C6-C7 bond of compound 7 improved cytotoxic activity, indicating
      that, in particular, the 6,7-seco-podocarpane-type compound 20 might serve as a
      lead compound for further development. 

PMID- 25075750
TI  - Shapes of interacting RNA complexes.
AB  - Shapes of interacting RNA complexes are studied using a filtration via their
      topological genus. A shape of an RNA complex is obtained by (iteratively)
      collapsing stacks and eliminating hairpin loops. This shape projection preserves
      the topological core of the RNA complex, and for fixed topological genus there
      are only finitely many such shapes. Our main result is a new bijection that
      relates the shapes of RNA complexes with shapes of RNA structures. This allows
      for computing the shape polynomial of RNA complexes via the shape polynomial of
      RNA structures. We furthermore present a linear time uniform sampling algorithm
      for shapes of RNA complexes of fixed topological genus.

PMID- 25075751
TI  - Continuous monitoring of enzymatic reactions on surfaces by real-time flow
      cytometry: sortase a catalyzed protein immobilization as a case study.
AB  - Only a few techniques, such as quartz crystal microbalance and surface plasmon
      resonance spectroscopy, enable the analysis of dynamic processes on solid
      supports. Here we have developed a straightforward assay based on flow cytometry
      to continuously follow enzymatic reactions directly on microparticle surfaces. We
      applied this real-time flow cytometry (RT-FCM) approach to study the covalent
      immobilization of green-fluorescent protein (GFPuv) on triglycine-modified
      polystyrene microbeads by the transpeptidase sortase A (SrtA) from Staphylococcus
      aureus. Though commonly treated as functionally identical catalysts, the SrtA
      variants SrtADelta59 and SrtADelta25, in which the N-terminal amino acid residues
      1-59 and 1-25 of the native enzyme are truncated, were shown to perform very
      differently with regard to this particular immobilization reaction. While
      SrtADelta59 efficiently catalyzed the covalent attachment of GFPuv to the surface
      (as indicated by a linear increase of microbead fluorescence), SrtADelta25 was
      essentially inactive. Besides the length of the N-terminal amino acid extension
      on the SrtA construct, the position of the hexahistidine tag at either the N- or
      C-terminus affected the efficiency of enzymatic protein immobilization. Apart
      from three enzyme variants containing the native core structure of SrtA, we also
      included three recently evolved mutants of SrtA in this comparative study. With
      these mutants we observed a rapid initial attachment of the GFPuv target protein
      to the microbeads. However, with proceeding reaction time, cleavage of the
      covalently immobilized target protein from the surface prevailed over the
      coupling reaction, consequently causing a decline of microbead fluorescence. In
      general, the RT-FCM approach used herein represents a powerful analytical tool
      for qualitative dynamic studies of many heterogeneous enzymatic reactions or
      other binding events that influence the fluorescence properties of microparticle
      surfaces.

PMID- 25075752
TI  - Switch strategies in antiretroviral therapy regimens.
AB  - Despite great advances in antiretroviral therapy in the last decade, several
      limitations still remain such as adverse effects, lack of adherence and drug-drug
      interactions. Switching antiretroviral therapy in stable, virologically
      suppressed patients with the aim of improving tolerability and convenience is an
      expanding strategy in clinical practice. Several factors need to be taken into
      consideration when switching a suppressive regimen, such as previous virologic
      failure, genetic barrier of the new regimen, prior duration of virologic
      suppression and expected level of adherence. The most frequently used strategies
      include reductions in the number of pills, drugs or doses. Although switching
      strategies may be useful, not all the regimens used in clinical practice are
      based on data from randomized clinical trials and some may not be the best option
      for certain patients; therefore, therapy should be individualized taking into
      consideration available information as well as patient and drug characteristics. 

PMID- 25075753
TI  - Efficient determination of protocatechuic acid in fruit juices by selective and
      rapid magnetic molecular imprinted solid phase extraction coupled with HPLC.
AB  - Magnetic molecular imprinted polymers (MMIPs) have been prepared as solid phase
      material to selectively extract protocatechuic acid (PCA) from fruit juices with
      high capacity and fast binding kinetics. The resulting MMIPs were characterized
      by TEM, FT-IR, TGA, and VSM. The adsorption process between PCA and MMIPs
      followed Langumuir adsorption isotherm with maximum adsorption capacity at 7.5
      mg/g and pseudo-second-order reaction kinetics with fast binding kinetics
      (equilibrium time at 40 min). In addition, the prepared MMIPs showed rapid
      magnetic separation (10 s) and reusability (retained 94.9% after six cycles).
      Subsequently, MMIPs were successfully applied for selective enrichment and
      determination of PCA from fruit juices (0.45 MUg/mL in grape juice but not
      detected in apple juice, pineapple juice, orange juice, and peach juice) with
      satisfactory recoveries (92-107%). The results indicated that synthesized MMIPs
      can be used for efficient and selective extraction of PCA from complex matrices. 

PMID- 25075754
TI  - Highly stretchable thermoset fibers and nonwovens using thiol-ene
      photopolymerization.
AB  - In this report, we describe the preparation and characterization of a new class
      of thermoset fibers with high elongation and elastic recovery. Integrating UV
      activated thiol-ene photopolymerization and electrospinning, we demonstrate an
      environmentally friendly single step approach to convert small monomeric
      precursor molecules into highly elastic fibers and nonwoven mats. The fibers were
      derived by in situ photopolymerization of a trifunctional vinyl ether monomer and
      a tetrafunctional thiol. Although thermosets often offer good chemical and
      thermal stability, these fibers also have a high average elongation at break of
      62%. The elastomeric nature of these vinyl-ether based fibers can be partly
      attributed to their subambient Tg and partly to the cross-link density, monomer
      structure, and resulting network homogeneity. Nonwoven mats of these fibers were
      also stretchable and exhibited a much higher elongation at break of about 85%.
      These thermoset stretchable fibers could have potential applications as textile,
      biomedical, hot chemical filtration, and composite materials. 

PMID- 25075755
TI  - Multinuclear group 4 catalysis: olefin polymerization pathways modified by strong
      metal-metal cooperative effects.
AB  - Polyolefins are produced today catalytically on a vast scale, and the
      manufactured polymers find use in everything from artificial limbs and
      food/medical packaging to automotive and electrical components and lubricants.
      Although polyolefin monomers are typically cheap (e.g., ethylene, propylene,
      alpha-olefins), the resulting polymer properties can be dramatically tuned by the
      particular polymerization catalyst employed, and reflect a rich interplay of
      macromolecular chemistry, materials science, and physics. For example, linear low
      density polyethylene (LLDPE), produced by copolymerization of ethylene with
      linear alpha-olefin comonomers such as 1-butene, 1-hexene, or 1-octene, has small
      but significant levels of short alkyl branches (C2, C4, C6) along the
      polyethylene backbone, and is an important technology material due to outstanding
      rheological and mechanical properties. In 2013, the total world polyolefin
      production was approximately 211 million metric tons, of which about 11% was
      LLDPE. Historically, polyolefins were produced using ill-defined but highly
      active heterogeneous catalysts composed of supported groups 4 or 6 species
      (usually halides) activated by aluminum alkyls. In 1963, Karl Ziegler and Giulio
      Natta received the Nobel Prize for these discoveries. Beginning in the late
      1980s, a new generation of group 4 molecule-based homogeneous olefin
      polymerization catalysts emerged from discoveries by Walter Kaminsky, a team led
      by James Stevens at The Dow Chemical Company, this Laboratory at Northwestern
      University, and a host of talented groups in Germany, Italy, Japan, the United
      Kingdom, and the United States. These new "single-site" catalysts and their
      activating cocatalysts were far better defined and more rationally tunable in
      terms of structure, mechanism, thermodynamics, and catalyst activity and
      selectivity than ever before possible. An explosion of research advances led to
      new catalysts, cocatalysts, deeper mechanistic understanding of both the
      homogeneous and heterogeneous systems, macromolecules with dramatically altered
      properties, and large-scale industrial processes. It is noteworthy that many
      metalloenzymes employ multiple active centers operating in close synergistic
      proximity to achieve high activity and selectivity. Such enzymes were the
      inspiration for the research discussed in this Account, focused on the properties
      of multimetallic olefin polymerization catalysts. Here we discuss how
      modifications in organic ligand architecture, metal...metal proximity, and
      cocatalyst can dramatically modify polyolefin molecular weight, branch structure,
      and selectively for olefinic comonomer enchainment. We first discuss bimetallic
      catalysts with identical group 4 metal centers and then heterobimetallic systems
      with either group 4 or groups 4 + 6 catalytic centers. We compare and contrast
      the polymerization properties of the bimetallic catalysts with their monometallic
      analogues, highlighting marked cooperative enchainment effects and unusual
      polymeric products possible via the proximate catalytic centers. Such
      multinuclear olefin polymerization catalysts exhibit the following distinctive
      features: (1) unprecedented levels of polyolefin branching; (2) enhanced
      enchainment selectivity for linear and encumbered alpha-olefin comonomers; (3)
      enhanced polyolefin tacticity and molecular weight; (4) unusual 1,2-insertion
      regiochemistry for styrenic monomers; (5) modified chain transfer kinetics, such
      as M-polymer beta-hydride transfer to the metal or incoming monomer; (6) LLDPE
      synthesis with a single binuclear catalyst and ethylene.

PMID- 25075756
TI  - Graphene oxide liquid crystals as a versatile and tunable alignment medium for
      the measurement of residual dipolar couplings in organic solvents.
AB  - Residual dipolar couplings (RDCs) have proven to be an invaluable anisotropic NMR
      parameter for the structural elucidation of complex biopolymers and organic
      molecules. However, a remaining bottleneck limiting its wider use by organic and
      natural product chemists is the lack of a range of easily applicable aligning
      media for diverse organic solvents. In this study, graphene oxide (GO) liquid
      crystals (LCs) were developed to induce partial orientation of organic molecules
      to allow RDC measurements. These LCs were determined to be maintainable at very
      low concentrations (as low as 1 mg/mL, corresponding to quadrupolar (2)H
      splittings ranging from 2.8 to 30 Hz and maximum (13)C-(1)H dipolar couplings of
      20 Hz for camphor in a CH3COCH3/water system) and to be remarkably stable and
      broadly compatible with aqueous and organic solvents such as dimethyl sulfoxide,
      CH3COCH3, and CH3CN. Moreover, compared with those for other alignment media,
      very clean and high-quality NMR spectra were acquired with the GO molecules in
      solution because of their rigidity and high molecular weight. The developed
      medium offers a versatile and robust method for RDC measurements that may
      routinize the RDC-based structure determination of organic molecules. 

PMID- 25075757
TI  - Palladium-catalyzed allylic esterification via C-C bond cleavage of a secondary
      homoallyl alcohol.
AB  - Palladium-catalyzed allylic esterifications of secondary homoallyl alcohols with
      acids via sequential retro-allylation and esterification are demonstrated,
      affording the corresponding allyl ester in up to 99% yield. The electron effect
      of the substituent of the secondary alcohol was found to be crucial to the
      selective C-C bond cleavage. 

PMID- 25075759
TI  - Enantioselective synthesis of (+)-penostatin E.
AB  - The first enantioselective total synthesis of penostatin E has been accomplished.
      Two highly efficient and diastereoselective reactions, a Hosomi-Sakurai
      allylation and an intramolecular Pauson-Khand reaction, were utilized for the
      construction of the basic carbon framework of the target molecule as the key
      steps. A late-stage introduction of the side chain and a successful base-promoted
      elimination reaction afforded an efficient synthetic route to (+)-penostatin E. 

PMID- 25075758
TI  - Red emitting, cucurbituril-capped, pH-responsive conjugated oligomer-based
      nanoparticles for drug delivery and cellular imaging.
AB  - Here we report the synthesis of nanoparticles based on a conjugated oligomer
      which is synthesized through Heck-coupling of divinylfluorene and
      dibromobenzothiodiazole monomers. These water dispersible nanoparticles emit in
      the region of red tailing to the near-infrared region of the spectrum with high
      fluorescent quantum yield and brightness. The nanoparticles were found to be
      stable in water for a prolonged time without forming any aggregates and could
      carry camptothecin, an anticancer drug with high loading efficiency. MTT cell
      viability studies performed with breast cancer cell lines showed that half
      maximal inhibitory concentration (IC50) values of nanoparticles for MCF7 and MDA
      MB-231 were 44.7 MUM and 24.8 MUM, respectively. In order to further decrease the
      cytotoxicity and increase the stability of nanoparticles, amine groups were
      disguised by capping with cucurbit[7]uril (CB7). Drug release studies showed that
      drugs were released at low pH (at 5.0) faster than physiological pH (7.4)
      confirming the pH-responsive nature of the nanoparticles. On the other hand, CB7
      capped drug-loaded nanoparticles regulated the release rate by providing slower
      release at pH 7.4 than the nanoparticles in the absence of CB7s. IC50 values for
      camptothecin in the presence of nanoparticles with or without CB7 were
      significantly reduced in MCF7 and MDA-MB-231 cells. 

PMID- 25075760
TI  - Radical or not radical: compared structures of metal (M = Ni, Au) bis-dithiolene
      complexes with a thiazole backbone.
AB  - A complete series of dianionic, monoanionic, and neutral dithiolene complexes
      formulated as [Ni(Et-thiazdt)2](n), with n = -2, -1, 0, and Et-thiazdt: N-ethyl
      1,3-thiazoline-2-thione-4,5-dithiolate, is prepared using an optimized procedure
      described earlier for the N-Me derivatives. Electrochemical and spectroscopic
      properties confirm the electron-rich character of the Et-thiazdt dithiolate
      ligand. The three complexes are structurally characterized by single-crystal X
      ray diffraction. The paramagnetic anionic complex [Ni(Et-thiazdt)2](-1), as
      Ph4P(+) salt, exhibits side-by-side lateral interactions leading to a Heisenberg
      spin chain behavior. The solid-state structure of the neutral, diamagnetic [Ni(Et
      thiazdt)2](0) complex shows a face-to-face organization with a large longitudinal
      shift, at variance with the structure of its radical and neutral gold dithiolene
      analogue described earlier and formulated as [Au(Et-thiazdt)2](*). Comparison of
      the two structures, and those of the other few structurally characterized pairs
      of Ni/Au dithiolene complexes, demonstrates the important role played by overlap
      interactions between gold dithiolene radical species. Despite its closed-shell
      character, the neutral nickel complex [Ni(Et-thiazdt)2](0) exhibits a
      semiconducting behavior with a room-temperature conductivity sigmaRT ~ 0.014 S
      cm(-1). 

PMID- 25075761
TI  - Isolation of MERS coronavirus from a dromedary camel, Qatar, 2014.
AB  - We obtained the full genome of Middle East respiratory syndrome coronavirus (MERS
      CoV) from a camel in Qatar. This virus is highly similar to the human
      England/Qatar 1 virus isolated in 2012. The MERS-CoV from the camel efficiently
      replicated in human cells, providing further evidence for the zoonotic potential
      of MERS-CoV from camels. 

PMID- 25075763
TI  - Your garden hose: a potential health risk due to Legionella spp. growth
      facilitated by free-living amoebae.
AB  - Common garden hoses may generate aerosols of inhalable size (<=10 MUm) during
      use. If humans inhale aerosols containing Legionella bacteria, Legionnaires'
      disease or Pontiac fever may result. Clinical cases of these illnesses have been
      linked to garden hose use. The hose environment is ideal for the growth and
      interaction of Legionella and free-living amoebae (FLA) due to biofilm formation,
      elevated temperatures, and stagnation of water. However, the microbial densities
      and hose conditions necessary to quantify the human health risks have not been
      reported. Here we present data on FLA and Legionella spp. detected in water and
      biofilm from two types of garden hoses over 18 months. By culturing and qPCR, two
      genera of FLA were introduced via the drinking water supply and reached mean
      densities of 2.5 log10 amoebae.mL(-1) in garden hose water. Legionella spp.
      densities (likely including pathogenic L. pneumophila) were significantly higher
      in one type of hose (3.8 log10 cells.mL(-1), p < 0.0001). A positive correlation
      existed between Vermamoebae vermiformis densities and Legionella spp. densities
      (r = 0.83, p < 0.028). The densities of Legionella spp. identified in the hoses
      were similar to those reported during legionellosis outbreaks in other
      situations. Therefore, we conclude that there is a health risk to susceptible
      users from the inhalation of garden hose aerosols. 

PMID- 25075762
TI  - Studies toward the Development of Antiproliferative Neoclerodanes from Salvinorin
      A.
AB  - The success rate for central nervous system (CNS) drug candidates in the clinic
      is relatively low compared to the industry average across other therapeutic
      areas. Penetration through the blood-brain barrier (BBB) to reach the therapeutic
      target is a major obstacle in development. The rapid CNS penetration of
      salvinorin A has suggested that the neoclerodane nucleus offers an excellent
      scaffold for developing antiproliferative compounds that enter the CNS. The
      Liebeskind-Srogl reaction was used as the main carbon-carbon bond-forming step
      toward the synthesis of quinone-containing salvinorin A analogues. Quinone
      containing salvinorin A analogues were shown to have antiproliferative activity
      against the MCF7 breast cancer cell line, but show no significant activity at the
      kappa-opioid receptors. In an in vitro model of BBB penetration, quinone
      containing salvinorin A analogues were shown to passively diffuse across the cell
      monolayer. The analogues, however, are substrates of P-glycoprotein, and thus
      further modification of the molecules is needed to reduce the affinity for the
      efflux transporter. 

PMID- 25075764
TI  - Comprehensive measures of sound exposures in cinemas using smart phones.
AB  - OBJECTIVES: Sensorineural hearing loss from sound overexposure has a considerable
      prevalence. Identification of sound hazards is crucial, as prevention, due to a
      lack of definitive therapies, is the sole alternative to hearing aids. One
      subjectively loud, yet little studied, potential sound hazard is movie theaters.
      This study uses smart phones to evaluate their applicability as a widely
      available, validated sound pressure level (SPL) meter. Therefore, this study
      measures sound levels in movie theaters to determine whether sound levels exceed
      safe occupational noise exposure limits and whether sound levels in movie
      theaters differ as a function of movie, movie theater, presentation time, and
      seat location within the theater. DESIGN: Six smart phones with an SPL meter
      software application were calibrated with a precision SPL meter and validated as
      an SPL meter. Additionally, three different smart phone generations were measured
      in comparison to an integrating SPL meter. Two different movies, an action movie
      and a children's movie, were measured six times each in 10 different venues (n =
      117). To maximize representativeness, movies were selected focusing on large
      release productions with probable high attendance. Movie theaters were selected
      in the San Francisco, CA, area based on whether they screened both chosen movies
      and to represent the largest variety of theater proprietors. Measurements were
      analyzed in regard to differences between theaters, location within the theater,
      movie, as well as presentation time and day as indirect indicator of film
      attendance. RESULTS: The smart phone measurements demonstrated high accuracy and
      reliability. Overall, sound levels in movie theaters do not exceed safe exposure
      limits by occupational standards. Sound levels vary significantly across theaters
      and demonstrated statistically significant higher sound levels and exposures in
      the action movie compared to the children's movie. Sound levels decrease with
      distance from the screen. However, no influence on time of day or day of the week
      as indirect indicator of film attendance could be found. CONCLUSIONS: Calibrated
      smart phones with an appropriate software application as used in this study can
      be utilized as a validated SPL meter. Because of the wide availability, smart
      phones in combination with the software application can provide high quantity
      recreational sound exposure measurements, which can facilitate the identification
      of potential noise hazards. Sound levels in movie theaters decrease with distance
      to the screen, but do not exceed safe occupational noise exposure limits.
      Additionally, there are significant differences in sound levels across movie
      theaters and movies, but not in presentation time.

PMID- 25075765
TI  - Clubfoot associated with preaxial polydactyly.
AB  - We report on three children with bilateral, congenital clubfoot. Four of the six
      clubfeet were associated with preaxial polydactyly. Five of the six clubfeet were
      treated without extensive surgery. A plantigrade foot was achieved, even in the
      three clubfeet with polydactyly, using serial casting and percutaneous Achilles
      tenotomy. Casting was adapted according to the existing polydactyly. One case
      with tibial hemimelia and a complex clubfoot deformity with preaxial tarsal
      polydactyly required more comprehensive surgery. A foot with good weight-bearing
      function was also achieved in this case following resection of the accessory
      medial ray, including resection of the accessory tarsal bones and posterior
      release. Remaining limitations in mobility were ascribed to hindfoot pathologies.

PMID- 25075766
TI  - Traumatic posterior hip dislocation and ipsilateral distal femoral fracture in a
      22-month-old child: a case report.
AB  - Minor trauma may cause hip dislocation in young children because of physiologic
      hip joint laxity and the soft cartilaginous structure of the acetabulum. In this
      work, we report on a 22-month-old boy with right-sided traumatic posterior hip
      dislocation and ipsilateral distal femoral fracture because of an outdoor motor
      vehicle accident. The patient was treated with emergency closed reduction and one
      and a half hip spica under general anaesthesia. The femoral fracture and hip
      dislocation were healed smoothly without any complication. Traumatic hip
      dislocation is rare in children, which may occur after trivial trauma. Prognosis
      is better in younger patients with low-energy trauma and in cases treated early. 

PMID- 25075767
TI  - How does rectus femoris fibrosis affect gait?
AB  - We report on a female patient with stiff-knee gait resulting from rectus femoris
      fibrosis, following multiple injections into the quadriceps musculature.
      Treatment planning and outcome were aided by instrumented three-dimensional gait
      analysis. One year after surgery, improvements were found in walking speed, step
      length, anterior pelvic tilt, knee flexion in swing, and ankle dorsiflexion in
      swing. Instrumented three-dimensional gait analysis was a useful tool for
      characterizing gait impairments and detecting changes after surgical
      intervention. Intramuscular injections into the rectus femoris muscle should be
      avoided to prevent stiff-knee gait and associated disability.

PMID- 25075768
TI  - Angiotensin(1-7) attenuates the progression of streptozotocin-induced diabetic
      renal injury better than angiotensin receptor blockade.
AB  - To explore the potential therapeutic effects of angiotensin(1-7) (Ang(1-7)), an
      endogenous ligand of the Mas receptor, on streptozotocin-induced diabetic
      nephropathy, male Wistar rats were randomly divided into two groups: a control
      group and a diabetic model group. After 12 weeks, the diabetic rats were divided
      into subgroups for 4-week treatments consisting of no-treatment group, small-,
      moderate-, and large-dose Ang(1-7) groups, a valsartan group, a large-dose Ang(1
      7) plus valsartan group, and an A779 (antagonist of the Mas receptor) group, each
      with 15 rats. Ang(1-7) improved renal function, attenuated glomeruli sclerosis,
      oxidative stress, and cell proliferation, decreased the expression of collagen
      IV, TGF-beta1, VEGF, NOX4, p47phox, PKCalpha, and PKCbeta1, and the
      phosphorylation of Smad3. In the rat mesangial HBZY-1 cell line, Ang(1-7)
      decreased high-glucose-induced oxidative stress, the proliferation and expression
      of NOX4, p47phox, and TGF-beta1, the phosphorylation of Smad3, collagen IV, and
      VEGF, and the membrane translocation of PKCalpha and PKCbeta1. A779 blocked the
      effects of Ang(1-7) both in vivo and in vitro. The effects of large-dose Ang(1-7)
      alone and in combination with valsartan were superior to valsartan alone, but the
      combination had no significant synergistic effect compared with Ang(1-7) alone.
      Thus, Ang(1-7) ameliorated streptozotocin-induced diabetic renal injury. Large
      dose treatment was superior to valsartan in reducing oxidative stress and
      inhibiting TGFbeta1/Smad3- and VEGF-mediated pathways. 

PMID- 25075769
TI  - Data from the Dialysis Outcomes and Practice Patterns Study validate an
      association between high intravenous iron doses and mortality.
AB  - Intravenous (IV) iron is required for optimal management of anemia in the
      majority of hemodialysis (HD) patients. While IV iron prescription has increased
      over time, the best dosing strategy is unknown and any effect of IV iron on
      survival is unclear. Here we used adjusted Cox regression to analyze associations
      between IV iron dose and clinical outcomes in 32,435 HD patients in 12 countries
      from 2002 to 2011 in the Dialysis Outcomes and Practice Patterns Study. The
      primary exposure was total prescribed IV iron dose over the first 4 months in the
      study, expressed as an average dose/month. Compared with 100-199 mg/month (the
      most common dose range), case-mix-adjusted mortality was similar for the 0, 1-99,
      and 200-299 mg/month categories but significantly higher for the 300-399 mg/month
      (HR of 1.13, 95% CI of 1.00-1.27) and 400 mg/month or more (HR of 1.18, 95% CI of
      1.07-1.30) groups. Convergent validity was proved by an instrumental variable
      analysis, using HD facility as the instrument, and by an analysis expressing IV
      iron dose/kg body weight. Associations with cause-specific mortality
      (cardiovascular, infectious, and other) were generally similar to those for all
      cause mortality. The hospitalization risk was elevated among patients receiving
      300 mg/month or more compared with 100-199 mg/month (HR of 1.12, 95% CI of 1.07
      1.18). In light of these associations, a well-powered clinical trial to evaluate
      the safety of different IV iron-dosing strategies in HD patients is urgently
      needed.

PMID- 25075771
TI  - Increased postdialysis systolic blood pressure is associated with extracellular
      overhydration in hemodialysis outpatients.
AB  - Recently, intradialytic hypertension was reported to be associated with increased
      mortality for hemodialysis patients. To determine whether volume status plays a
      role in dialysis-associated hypertension, we prospectively audited 531 patients
      that had volume assessments measured by multiple-frequency bioelectrical
      impedance during their midweek dialysis session. Mean pre- and postdialysis
      weights were 73.2 vs 71.7 kg, and systolic blood pressures (SBPs) 140.5 vs. 130.3
      mm Hg, respectively. Patients were divided into groups based on a fall in SBP of
      20 mm Hg or more (32%), an increased SBP of 10 mm Hg or more (18%), and a stable
      group (50%). There were no differences in patient demographics, dialysis
      prescriptions, predialysis weight, total body (TBW), and extracellular (ECW) and
      intracellular water (ICW). However, the change in weight was significantly less
      in the increased blood pressure group (1.01 kg vs. stable 1.65, and 1.7
      hypotensive). The ratio of ECW to TBW was significantly higher in the increased
      blood pressure group, particularly post dialysis (39.1 vs. stable 38.7% and fall
      in blood pressure group 38.7%). ECW overhydration was significantly greater in
      the increased blood pressure group post dialysis (0.7 (0.17 to 1.1) vs. stable
      0.39 (-0.2 to 0.95) and fall in blood pressure group 0.38 (-0.19 to 0.86) liter).
      We found that patients who had increased blood pressure post dialysis had greater
      hydration status, particularly ECW. Thus, patients who increase their blood
      pressure post dialysis should have review of target weight, consideration of
      lowering the post-dialysis weight, and may benefit from increasing dialysis
      session time or frequency. 

PMID- 25075770
TI  - Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic
      nephropathy.
AB  - Diabetic nephropathy is a growing health concern with characteristic sterile
      inflammation. As the underlying mechanisms of this inflammation remain poorly
      defined, specific therapies targeting sterile inflammation in diabetic
      nephropathy are lacking. Intriguingly, an association of diabetic nephropathy
      with inflammasome activation has recently been shown, but the pathophysiological
      relevance of this finding remains unknown. Within glomeruli, inflammasome
      activation was detected in endothelial cells and podocytes in diabetic humans and
      mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro.
      Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to
      protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are
      protected against diabetic nephropathy despite transplantation of wild-type bone
      marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic
      nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the
      Nlrp3 inflammasome in glucose or advanced glycation end product stressed
      podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome
      activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3
      inflammasome activation in non-myeloid-derived cells aggravate diabetic
      nephropathy. Targeting the inflammasome may be a potential therapeutic approach
      to diabetic nephropathy. 

PMID- 25075772
TI  - Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary
      tract.
AB  - Recent evidence suggests antimicrobial peptides protect the urinary tract from
      infection. Ribonuclease 7 (RNase 7), a member of the RNase A superfamily, is a
      potent epithelial-derived protein that maintains human urinary tract sterility.
      RNase 7 expression is restricted to primates, limiting evaluation of its
      antimicrobial activity in vivo. Here we identified ribonuclease 6 (RNase 6) as
      the RNase A superfamily member present in humans and mice that is most conserved
      at the amino acid level relative to RNase 7. Like RNase 7, recombinant human and
      murine RNase 6 has potent antimicrobial activity against uropathogens.
      Quantitative real-time PCR and immunoblot analysis indicate that RNase 6 mRNA and
      protein are upregulated in the human and murine urinary tract during infection.
      Immunostaining located RNase 6 to resident and infiltrating monocytes,
      macrophages, and neutrophils. Uropathogenic E. coli induces RNase 6 peptide
      expression in human CD14(+) monocytes and murine bone marrow-derived macrophages.
      Thus, RNase 6 is an inducible, myeloid-derived protein with markedly different
      expression from the epithelial-derived RNase 7 but with equally potent
      antimicrobial activity. Our studies suggest RNase 6 serves as an evolutionarily
      conserved antimicrobial peptide that participates in the maintenance of urinary
      tract sterility. 

PMID- 25075773
TI  - Remote ischemic preconditioning has a neutral effect on the incidence of kidney
      injury after coronary artery bypass graft surgery.
AB  - Acute kidney injury (AKI) is a frequent complication of cardiac surgery and
      usually occurs in patients with preexisting chronic kidney disease (CKD). Remote
      ischemic preconditioning (RIPC) may mitigate the renal ischemia-reperfusion
      injury associated with cardiac surgery and may be a preventive strategy for
      postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent
      AKI in 86 patients with CKD (estimated glomerular filtration rate under 60 ml/min
      per 1.73 m(2)) undergoing coronary artery bypass graft (CABG) surgery. Forty
      three patients each were randomized to receive standard care with or without RIPC
      consisting of three 5-minute cycles of forearm ischemia followed by reperfusion.
      The primary end point was the development of AKI defined as an increase in serum
      creatinine concentration over 0.3 mg/dl within 48 h of surgery. Secondary end
      points included a comparison between the study and control groups of several
      serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase
      associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers
      including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24 h
      after CABG, and the 72-h serum troponin T concentration area under the curve as a
      marker of myocardial injury. Clinical and operative characteristics were similar
      between the preconditioned and control groups. AKI developed in 12 patients in
      both groups within 48 h of CABG. There were no significant differences between
      the two groups in the concentrations of any of the serum or urinary biomarkers of
      renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia
      reperfusion had no effect on the frequency of AKI after CABG in patients with
      CKD. 

PMID- 25075774
TI  - [Dance sport: injury profile in Latin American formation dancing].
AB  - BACKGROUND: Latin American formation dancing ranks among the technical
      compositional types of sport and represents a discipline of dance sport due to
      its performance- and competition-orientated mode. Despite its high degree of
      popularity and a movement profile favouring injuries, there has been a lack of
      studies as to health hazards and damage in Latin American formation dancing. The
      aim of this study is to analyse formation dance-related health hazards and their
      causes. METHODS: A total of n = 100 (m: n = 52, f: n = 48) Latin American dancers
      of the German top-level league participated in this anonymised retrospective
      cross-sectional investigation. RESULTS: Mean weights of the male dancers were
      75.2 kg and respectively 58.2 kg for the females, mean body height/size were 1.82
      m (m) and 1.67 m (f) and mean BMI 22.2 (m) and 20.0 (f), respectively. At least
      one each traumatic injury/chronic damage was sustained by 69.3 % (m) and 77.6 %
      (f) of the dancers in the course of their dance sport activities. Almost all
      (97.9 %) injuries occurred during the training. A total of 409 injuries/overuse
      damages (= 4.1 injuries/athlete) was reported with 80.4 % traumatic injuries and
      19.5 % chronic damages. Female dancers were more often injured than their male
      counterparts. The lower extremity was the most commonly affected body region
      [64.5 % (m) and, respectively, 71.2 % (f)], followed by upper extremity (m: 21.2
      %, f: 17.6 %) and spinal column/trunk region (m: 12.0 %, f: 8.5 %). Blockages and
      pulled muscles were the most common complaints reported by males with contusions
      and pulled muscles being reported by females. Chondropathy/osteoarthrosis were
      the most frequent chronic diseases. Of all injuries sustained, circa two thirds
      were caused by extrinsic and circa one third by intrinsic factors. CONCLUSION:
      The injury profiles/patterns in Latin American formation dancing show on the one
      hand parallels to the individual partner dances. On the other hand, typical and
      gender-specific movement elements seem to reflect in the injuries and chronic
      damages/diseases of formation dancers. This is to be taken into account when
      injury prevention measures are considered. There is also a need for further
      studies to allow a more differentiated analysis.

PMID- 25075775
TI  - Synthesis, magnetic properties and dynamic behavior of cobalt complexes with an
      anthracene-containing dioxolene ligand.
AB  - The anthracene-functionalized cobalt complexes [Co(L)(TPA)]PF6 (1) and
      [Co(L)(Me(n)TPA)]PF6 (2, n = 1; 3, n = 2; 4, n = 3) were synthesized by the
      combination of 9-(3,4-dihydroxyphenyl)anthracene (H2L) and tris(2
      pyridylmethyl)amine (TPA) or its derivatives (Me(n)TPA, n = 1, 2, 3).
      Characterization of complexes 1-4 was performed by UV-vis absorption, IR, (1)H
      NMR, and magnetic susceptibility measurements. In the solid state, the variable
      temperature magnetic susceptibility data showed that complex 1 is low-spin
      cobalt(III) catecholate (Co(III)(LS)-Cat), while complex 4 is high-spin
      cobalt(II) semiquinonate (Co(II)(HS)-SQ) in the range 4.5-400 K. The
      susceptibility data of complexes 2 and 3 suggested valence tautomerism between
      the Co(III)(LS)-Cat and Co(II)(HS)-SQ forms. Light-induced valence tautomerism
      was observed in complexes 2 and 3 at 5 K by photo-irradiation. In solution, the
      temperature dependence of (1)H NMR spectra of 1 and 2 showed an equilibrium
      between their geometrical isomers.

PMID- 25075776
TI  - Impaired subjective well-being in schizophrenia is associated with reduced
      anterior cingulate activity during reward processing.
AB  - BACKGROUND: Patients with schizophrenia have substantially reduced subjective
      well-being (SW) compared to healthy individuals. It has been suggested that
      diminished SW may be related to deficits in the neural processing of reward but
      this has not been shown directly. We hypothesized that, in schizophrenia, lower
      SW would be associated with attenuated reward-related activation in the reward
      network. METHOD: Twenty patients with schizophrenia with a range of SW underwent
      a functional magnetic resonance imaging (fMRI) reward task. The brain activity
      underlying reward anticipation and outcome in schizophrenia was examined and
      compared to that of 12 healthy participants using a full factorial analysis.
      Region of interest (ROI) analyses of areas within the reward network and whole
      brain analyses were conducted to reveal neural correlates of SW. RESULTS: Reward
      related neural activity in schizophrenia was not significantly different from
      that of healthy participants; however, the patients with schizophrenia showed
      significantly diminished SW. Both ROI and whole-brain analyses confirmed that SW
      scores in the patients correlated significantly with activity, specifically in
      the dorsal anterior cingulate cortex (dACC), during both reward anticipation and
      reward outcome. This association was not seen in the healthy participants.
      CONCLUSIONS: In patients with schizophrenia, reduced activation of the dACC
      during multiple aspects of reward processing is associated with lower SW. As the
      dACC has been widely linked to coupling of reward and action, and the link to SW
      is apparent over anticipation and outcome, these findings suggest that SW
      deficits in schizophrenia may be attributable to reduced integration of
      environmental rewarding cues, motivated behaviour and reward outcome.

PMID- 25075777
TI  - Long-term surgical versus functional Class II correction: a comparison of
      identical twins.
AB  - The purpose of this twin case comparison was to assess the short- and long-term
      effects of nonsurgical treatment vs orthognathic surgical treatment for Class II
      correction. Two identical twins (age 13 years 3 months) were treated for Class II
      correction where one patient was treated nonsurgically using a fixed functional
      appliance, while the other was treated using orthognathic mandibular advancement
      surgery. The patients were recalled and evaluated 5 years in retention. Comparing
      changes in the short and long term, surgical treatment led to superior skeletal
      results compared to the nonsurgical twin. However, the soft tissue profile was
      remarkably similar for both patients suggesting that soft tissue profile changes
      may not necessarily follow similar changes in the bony skeletal structures.

PMID- 25075778
TI  - Arsenite induces neurotoxic effects on AFD neurons via oxidative stress in
      Caenorhabditis elegans.
AB  - Arsenic permeates our environment. As a result, humans are continually exposed to
      it. This study investigates the possible roles of oxidative stress in arsenite
      (As(III))-induced neurotoxicity in Caenorhabditis elegans. Exposure to As(III),
      at the concentrations examined, caused a decrease in locomotor behaviors
      (frequencies of body bends, head thrashes, and reversals) of C. elegans. In
      addition, As(III) exposure (100 MUM) decreased thermotactic behaviors, and
      induced severe deficits in the structural properties of AFD sensory neurons.
      Exposure to As(III) (100 MUM) also caused an elevated production of intracellular
      reactive oxygen species (ROS) in wild-type C. elegans. Pretreatment with the
      antioxidant curcumin ameliorated the decrease in locomotor and thermotactic
      behavior, the formation of deficits in the structural properties of AFD sensory
      neurons, and intracellular ROS in As(III)-exposed nematodes. Our study suggests
      that oxidative stress plays a crucial role in the As(III)-induced neurotoxic
      effects on locomotor behavior and the structures and function of AFD sensory
      neurons in As(III)-exposed nematodes.

PMID- 25075779
TI  - Eosinophilic meningitis caused by Angiostrongylus cantonensis: an emergent
      disease in Brazil.
AB  - Eosinophilic meningitis (EoM) is an acute disease that affects the central
      nervous system. It is primarily caused by infection with the nematode
      Angiostrongylus cantonensis. This infection was previously restricted to certain
      Asian countries and the Pacific Islands, but it was first reported in Brazil in
      2007. Since then, intermediate and definitive hosts infected with A. cantonensis
      have been identified within the urban areas of many states in Brazil, including
      those in the northern, northeastern, southeastern and southern regions. The goals
      of this review are to draw the attention of the medical community and health
      centres to the emergence of EoM in Brazil, to compile information about several
      aspects of the human infection and mode of transmission and to provide a short
      protocol of procedures for the diagnosis of this disease. 

PMID- 25075780
TI  - Water-induced modulation of Helicobacter pylori virulence properties.
AB  - While the influence of water in Helicobacter pylori culturability and membrane
      integrity has been extensively studied, there are little data concerning the
      effect of this environment on virulence properties. Therefore, we studied the
      culturability of water-exposed H. pylori and determined whether there was any
      relation with the bacterium's ability to adhere, produce functional components of
      pathogenicity and induce inflammation and alterations in apoptosis in an
      experimental model of human gastric epithelial cells. H. pylori partially
      retained the ability to adhere to epithelial cells even after complete loss of
      culturability. However, the microorganism is no longer effective in eliciting in
      vitro host cell inflammation and apoptosis, possibly due to the non-functionality
      of the cag type IV secretion system. These H. pylori-induced host cell responses,
      which are lost along with culturability, are known to increase epithelial cell
      turnover and, consequently, could have a deleterious effect on the initial H.
      pylori colonisation process. The fact that adhesion is maintained by H. pylori to
      the detriment of other factors involved in later infection stages appears to
      point to a modulation of the physiology of the pathogen after water exposure and
      might provide the microorganism with the necessary means to, at least
      transiently, colonise the human stomach. 

PMID- 25075781
TI  - Tissue distribution of residual antimony in rats treated with multiple doses of
      meglumine antimoniate.
AB  - Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony
      (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are
      first-choice drugs for the treatment of leishmaniases, there are gaps in our
      knowledge of their toxicological profile, mode of action and kinetics. Little is
      known about the distribution of antimony in tissues after SbV administration. In
      this study, we evaluated the Sb content of tissues from male rats 24 h and three
      weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d,
      subcutaneous). Sb concentrations in the blood and organs were determined by
      inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb
      blood levels after MA dosing can be described by a two-compartment model with a
      fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was
      the organ that accumulated the highest amount of Sb, while bone and thyroid
      ranked second in descending order of tissues according to Sb levels (spleen >>
      bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus,
      pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain).
      The pathophysiological consequences of Sb accumulation in the thyroid and Sb
      speciation in the liver, thyroid, spleen and bone warrant further studies. 

PMID- 25075782
TI  - Acute gastroenteritis and enteric viruses in hospitalised children in southern
      Brazil: aetiology, seasonality and clinical outcomes.
AB  - Viral acute gastroenteritis (AG) is a significant cause of hospitalisation in
      children younger than five years. Group A rotavirus (RVA) is responsible for 30%
      of these cases. Following the introduction of RVA immunisation in Brazil in 2006,
      a decreased circulation of this virus has been observed. However, AG remains an
      important cause of hospitalisation of paediatric patients and only limited data
      are available regarding the role of other enteric viruses in these cases. We
      conducted a prospective study of paediatric patients hospitalised for AG. Stool
      samples were collected to investigate human adenovirus (HAdV), RVA, norovirus
      (NoV) and astrovirus (AstV). NoV typing was performed by nucleotide sequencing
      and phylogenetic analysis. From the 225 samples tested, 60 (26%) were positive
      for at least one viral agent. HAdV, NoV, RVA and AstV were detected in 16%, 8%,
      6% and 0% of the samples, respectively. Mixed infections were found in nine
      patients: HAdV/RVA (5), HAdV/NoV (3) and HAdV/NoV/RVA (1). The frequency of fever
      and lymphocytosis was significantly higher in virus-infected patients.
      Phylogenetic analysis of NoV indicated that all of these viruses belonged to
      genotype GII.4. The significant frequency of these pathogens in patients with AG
      highlights the need to routinely implement laboratory investigations. 

PMID- 25075783
TI  - Molecular epidemiology of Candida albicans and Candida glabrata strains isolated
      from intensive care unit patients in Poland.
AB  - Over the last decades, Candida spp have been responsible for an increasing number
      of infections, especially in patients requiring intensive care. Knowledge of
      local epidemiology and analysis of the spread of these pathogens is important in
      understanding and controlling their transmission. The aim of this study was to
      evaluate the genetic diversity of 31 Candida albicans and 17 Candida glabrata
      isolates recovered from intensive care unit patients from the tertiary hospital
      in Krakow between 2011-2012. The strains were typed by random amplified
      polymorphic DNA (RAPD) polymerase chain reaction using five primers (CD16AS,
      HP1247, ERIC-2, OPE-3 and OPE-18). The results of the present investigation
      revealed a high degree of genetic diversity among the isolates. No clonal
      relationship was found among the C. albicans strains, whereas two C. glabrata
      isolates were identical. The source of Candida infection appeared to be mostly
      endogenous; however, the presence of two clonal C. glabrata strains suggested the
      possibility of cross-transmission of these pathogens. Our study confirmed the
      high discriminatory power of the RAPD technique in the molecular typing of
      Candida clinical isolates. This method may be applied to the evaluation of
      transmission routes of pathogenic fungi on a local level. 

PMID- 25075785
TI  - Morphology of the larvae, male genitalia and DNA sequences of Anopheles
      (Kerteszia) pholidotus (Diptera: Culicidae) from Colombia.
AB  - Since 1984, Anopheles (Kerteszia) lepidotus has been considered a mosquito
      species that is involved in the transmission of malaria in Colombia, after having
      been incriminated as such with epidemiological evidence from a malaria outbreak
      in Cunday-Villarrica, Tolima. Subsequent morphological analyses of females
      captured in the same place and at the time of the outbreak showed that the
      species responsible for the transmission was not An. lepidotus, but rather
      Anopheles pholidotus. However, the associated morphological stages and DNA
      sequences of An. pholidotus from the foci of Cunday-Villarrica had not been
      analysed. Using samples that were caught recently from the outbreak region, the
      purpose of this study was to provide updated and additional information by
      analysing the morphology of female mosquitoes, the genitalia of male mosquitoes
      and fourth instar larvae of An. pholidotus, which was confirmed with DNA
      sequences of cytochrome oxidase I and rDNA internal transcribed spacer. A total
      of 1,596 adult females were collected in addition to 37 larval collections in
      bromeliads. Furthermore, 141 adult females, which were captured from the same
      area in the years 1981-1982, were analysed morphologically. Ninety-five DNA
      sequences were analysed for this study. Morphological and molecular analyses
      showed that the species present in this region corresponds to An. pholidotus.
      Given the absence of An. lepidotus, even in recent years, we consider that the
      species of mosquitoes that was previously incriminated as the malaria vector
      during the outbreak was indeed An. pholidotus, thus ending the controversy. 

PMID- 25075784
TI  - Sympathetic glial cells and macrophages develop different responses to
      Trypanosoma cruzi infection or lipopolysaccharide stimulation.
AB  - Nitric oxide (NO) participates in neuronal lesions in the digestive form of
      Chagas disease and the proximity of parasitised glial cells and neurons in
      damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles
      in many neuropathological situations and are potential sources of NO. Here, we
      investigate peripheral glial cell response to Trypanosoma cruzi infection to
      clarify the role of these cells in the neuronal lesion pathogenesis of Chagas
      disease. We used primary glial cell cultures from superior cervical ganglion to
      investigate cell activation and NO production after T. cruzi infection or
      lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T.
      cruzi infection was greater in glial cells, despite similar levels of NO
      production in both cell types. Glial cells responded similarly to T. cruzi and
      LPS, but were less responsive to LPS than macrophages were. Our observations
      contribute to the understanding of Chagas disease pathogenesis, as based on the
      high susceptibility of autonomic glial cells to T. cruzi infection with
      subsequent NO production. Moreover, our findings will facilitate future research
      into the immune responses and activation mechanisms of peripheral glial cells,
      which are important for understanding the paradoxical responses of this cell type
      in neuronal lesions and neuroprotection. 

PMID- 25075786
TI  - In vivo assessment of antiretroviral therapy-associated side effects.
AB  - Antiretroviral therapy has been associated with side effects, either from the
      drug itself or in conjunction with the effects of human immunodeficiency virus
      infection. Here, we evaluated the side effects of the protease inhibitor (PI)
      indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment
      increased the hamster death rate and resulted in an increase in triglyceride,
      cholesterol and glucose serum levels and a reduction in anti-oxLDL auto
      antibodies. The treatment led to histopathological alterations of the kidney and
      the heart. These results suggest that hamsters are an interesting model for the
      study of the side effects of antiretroviral drugs, such as PIs. 

PMID- 25075787
TI  - Incipient colonisation of Lutzomyia longipalpis in the city of Resistencia,
      province of Chaco, Argentina (2010-2012).
AB  - Lutzomyia longipalpis was recorded for the first time in Argentina in 2004, in
      the province of Formosa. In the following years, the vector spread to the south
      and west in the country and was recorded in the province of Chaco in 2010. From
      November 2010-May 2012, captures of Phlebotominae were made in the city of
      Resistencia and its surroundings, to monitor the spread and possible colonisation
      of Lu. longipalpis in the province of Chaco. In this monitoring, Lu. longipalpis
      was absent in urban sampling sites and its presence was restricted to Barrio de
      los Pescadores. This suggests that the incipient colonisation observed in 2010
      was not followed by continuous installation of vector populations and expansion
      of their spatial distribution as in other urban centres of Argentina. 

PMID- 25075788
TI  - A four-year surveillance program for detection of Plasmodium falciparum
      chloroquine resistance in Honduras.
AB  - Countries could use the monitoring of drug resistance in malaria parasites as an
      effective early warning system to develop the timely response mechanisms that are
      required to avert the further spread of malaria. Drug resistance surveillance is
      essential in areas where no drug resistance has been reported, especially if
      neighbouring countries have previously reported resistance. Here, we present the
      results of a four-year surveillance program based on the sequencing of the pfcrt
      gene of Plasmodium falciparum populations from endemic areas of Honduras. All
      isolates were susceptible to chloroquine, as revealed by the pfcrt "CVMNK"
      genotype in codons 72-76. 

PMID- 25075789
TI  - Mitochondrial genome sequence diversity of Indian Plasmodium falciparum isolates.
AB  - We have analysed the whole mitochondrial (mt) genome sequences (each ~6 kilo
      nucleotide base pairs in length) of four field isolates of the malaria parasite
      Plasmodium falciparum collected from different locations in India. Comparative
      genomic analyses of mt genome sequences revealed three novel India-specific
      single nucleotide polymorphisms. In general, high mt genome diversity was found
      in Indian P. falciparum, at a level comparable to African isolates. A population
      phylogenetic tree placed the presently sequenced Indian P. falciparum with the
      global isolates, while a previously sequenced Indian isolate was an outlier.
      Although this preliminary study is limited to a few numbers of isolates, the data
      have provided fundamental evidence of the mt genome diversity and evolutionary
      relationships of Indian P. falciparum with that of global isolates. 

PMID- 25075790
TI  - Outstanding insecurities concerning the use of an Ov16-based ELISA in the
      Amazonia onchocerciasis focus.
AB  - In a recent issue of Memorias do Instituto Oswaldo Cruz, published in Rio de
      Janeiro in February 2014 (109: 87-92), Adami et al. have published a survey
      reporting Mansonella parasite prevalence in the Amazon Region. This report makes
      a useful contribution to the existing knowledge of filarial parasite distribution
      within the Amazon area, parasite prevalence rates in relation to age and
      occupation and provides observations on the possible clinical impact of
      Mansonella ozzardi. Their publication also provides an account of what appears to
      be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis
      Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are
      concerned that the publication of this ELISA may have created an excessively
      positive impression of the effectiveness of the onchocerciasis recrudescence
      serological surveillance tools that are presently available for use in the
      Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight
      some of the limitations of this ELISA and suggest how continuing insecurities
      concerning the detection of antibodies to Onchocerca volvulus within the Amazonia
      onchocerciasis focus might be minimised.

PMID- 25075792
TI  - The dynamics of p53 in single cells: physiologically based ODE and reaction
      diffusion PDE models.
AB  - The intracellular signalling network of the p53 protein plays important roles in
      genome protection and the control of cell cycle phase transitions. Recently
      observed oscillatory behaviour in single cells under stress conditions has
      inspired several research groups to simulate and study the dynamics of the
      protein with the aim of gaining a proper understanding of the physiological
      meanings of the oscillations. We propose compartmental ODE and PDE models of p53
      activation and regulation in single cells following DNA damage and we show that
      the p53 oscillations can be retrieved by plainly involving p53-Mdm2 and ATM-p53
      Wip1 negative feedbacks, which are sufficient for oscillations experimentally,
      with no further need to introduce any delays into the protein responses and
      without considering additional positive feedback. 

PMID- 25075793
TI  - Dynamic assessment of narrative ability in English accurately identifies language
      impairment in English language learners.
AB  - PURPOSE: To assess the identification accuracy of dynamic assessment (DA) of
      narrative ability in English for children learning English as a 2nd language.
      METHOD: A DA task was administered to 54 children: 18 Spanish-English-speaking
      children with language impairment (LI); 18 age-, sex-, IQ- and language
      experience-matched typical control children; and an additional 18 age- and
      language experience-matched comparison children. A variety of quantitative and
      qualitative measures were collected in the pretest phase, the mediation phase,
      and the posttest phase of the study. Exploratory discriminant analysis was used
      to determine the set of measures that best differentiated among this group of
      children with and without LI. RESULTS: A combination of examiner ratings of
      modifiability (compliance, metacognition, and task orientation), DA story scores
      (setting, dialogue, and complexity of vocabulary), and ungrammaticality (derived
      from the posttest narrative sample) classified children with 80.6% to 97.2%
      accuracy. CONCLUSION: DA conducted in English provides a systematic means for
      measuring learning processes and learning outcomes, resulting in a clinically
      useful procedure for identifying LIs in bilingual children who are in the process
      of learning English as a second language.

PMID- 25075794
TI  - Luteolin potentiates the sensitivity of colorectal cancer cell lines to
      oxaliplatin through the PPARgamma/OCTN2 pathway.
AB  - Oxaliplatin is a chemotherapeutic agent used in the treatment of colorectal
      cancers. However, the mechanism controlling the cellular uptake and efflux of
      oxaliplatin is not completely understood. Organic cation/carnitine transporter 2
      (OCTN2) is a member of the solute carrier superfamily and is a determinant of
      oxaliplatin uptake. OCTN2 is regulated by peroxisome proliferator-activated
      receptor gamma (PPARgamma) binding to the PPAR-response element within the first
      intron. Luteolin is a naturally occurring flavonoid and an agonist of PPARgamma.
      Thus, we hypothesize that luteolin-mediated OCTN2 expression and activity
      potentiate the sensitivity of cancer cells to oxaliplatin. In this study,
      luteolin increased mRNA and protein expression of OCTN2 in a time-dependent and
      dose-dependent manner in colorectal cancer SW480 cells. This induction was
      attenuated by PPARgamma antagonist GW9662 as well as by PPARgamma knockdown,
      suggesting that the induction by luteolin is dependent on PPARgamma. In uptake
      studies, luteolin increased the binding affinity of OCTN2 toward oxaliplatin and
      enhanced intracellular concentration of oxaliplatin. This finding is likely
      because of the increase of PDZ domain containing 1 (PDZK1) and PDZ domain
      containing 3 (PDZK2), which are known to facilitate the expression of OCTN2 on
      the cell surface and/or enhance transporter activity. Moreover, cell viability
      and cell apoptosis assays showed that luteolin increased oxaliplatin uptake and
      intracellular accumulation through OCTN2. Thus, our study showed that luteolin
      increased the sensitivity of colorectal cancer SW480 cells to oxaliplatin, likely
      through the PPARgamma/OCTN2 pathway. 

PMID- 25075795
TI  - Oridonin inhibits mTOR signaling and the growth of lung cancer tumors.
AB  - Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been widely
      used for treatment of various types of cancer. It has been shown that oridonin
      produced an antiproliferative effect in a lung cancer cell line in vitro.
      However, the antitumor effects of oridonin in lung cancer cells xenograft mice
      were poorly understood. The aim of the current study was to investigate the
      antitumor activity of oridonin in vivo and the molecular mechanisms mediating
      this antitumor efficacy. The human A549 and NCI-H292 non-small cell lung cancer
      cell lines were transferred to nude mice for the establishment of xenograft
      models. The results showed that oridonin (10, 20, 40 mg/kg, intraperitoneally)
      treatment for 28 days significantly decreased tumor volume and induced tumor
      growth inhibition in both A549 and NCI-H292 xenograft mice. Furthermore, oridonin
      promoted apoptosis by increasing terminal dUTP nick end labeling-positive cells
      as well as the ratio of Bax/Bcl-2 in xenograft mice. In addition, chronic
      oridonin administration inhibited mammalian target of rapamycin (mTORC1) activity
      by reduction of p-mTOR and p-p70s6k levels, suggesting that the increased
      apoptosis triggered by oridonin administration was associated with the
      downregulation of mTORC1 activity. Moreover, inhibition of mTORC1 by rapamycin (2
      mg/kg, intraperitoneally) enhanced the anticancer activity of oridonin in mice
      xenograft models. These findings indicate that treatment with oridonin exhibited
      antitumor actions through induction of apoptotic response by inhibition of mTORC1
      function. Our results also proposed the potential that inhibition of mTORC1 might
      be an effective target for increasing the therapeutic outcome in lung cancer
      patients treated with oridonin.

PMID- 25075796
TI  - Response to trabectedin in a patient with advanced synovial sarcoma with lung
      metastases.
AB  - Trabectedin is an alkylating agent registered in Europe for the treatment of
      advanced metastatic soft-tissue sarcomas, whose activity has been documented
      mainly in liposarcomas or leiomyosarcomas. Here, we report the response achieved
      in a patient with lung metastases from synovial sarcoma. A man with a large
      synovial sarcoma of the axilla underwent three cycles of neoadjuvant
      epirubicin+ifosfamide before complete excision, followed by three additional
      cycles of chemotherapy and radiotherapy. After 14 months, bilateral lung
      metastases appeared and were first treated with a prolonged 14-day continuous
      infusion of high-dose ifosfamide without response, and then with second-line
      trabectedin. A partial radiological response was achieved; dosage was reduced to
      1.1 mg/m because of mild asthenia, grade 3 neutropenia, grade 3 nausea and
      vomiting, and reversible transaminase elevation. After 9 months of treatment, the
      lung nodules progressed, the patient received sorafenib, but further progressed
      and died 19 months after the first appearance of lung metastases. Trabectedin was
      the only drug that led to a radiological response in this patient with synovial
      sarcoma, despite being administered at 75% of the standard dose because of dose
      limiting nausea and vomiting, in line with more recent data demonstrating
      activity in translocated sarcomas. We believe that trabectedin represents an
      attractive option for the treatment of metastatic synovial sarcoma and further
      clinical studies are warranted.

PMID- 25075797
TI  - Renal cell cancer metastases to esophagus and stomach successfully treated with
      radiotherapy and pazopanib.
AB  - Renal cell cancer has been rarely reported as a cause of gastric or esophageal
      metastases. They usually present with gastrointestinal bleeding and most cases
      have been managed surgically or endoscopically. We report the case of a 38-year
      old man with a 4-year history of metastatic renal cell carcinoma admitted to the
      emergency room with melena and anemia. At endoscopy, three esophageal polypoid
      lesions (middle and distal thirds) and a 7 cm mass in the gastric fundus were
      identified. Biopsy revealed esophageal mucosa infiltrated by renal cell
      carcinoma. Radiotherapy was administered (30 Gy in 10 fractions), followed by
      pazopanib, with excellent tolerance and without new bleeding episodes. Computed
      tomography scan showed complete disappearance of the esophageal and fundic
      lesions at 3 months follow-up. Twenty-four months after being initiated on
      pazopanib, there is no radiological evidence of disease. This is the first
      reported case showing complete remission of gastric and esophageal metastases
      after treatment with radiotherapy and pazopanib.

PMID- 25075798
TI  - AAP: Toxic stress threatens kids' long-term health.

PMID- 25075801
TI  - A direct comparison of active and passive amplification electrodes in the same
      amplifier system.
AB  - BACKGROUND: Active amplification electrodes are becoming more popular for ERP
      data collection, as they amplify the EEG at the scalp and thereby potentially
      decrease the influence of ambient electrical noise. However, the performance of
      active electrodes has not been directly compared with that of passive electrodes
      in the context of collecting ERPs from a cognitive task. Here, the performance of
      active and passive amplification electrodes in the same digitizing amplifier
      system was examined. METHOD: In Experiment 1, interelectrode impedance in an
      electrically quiet setting was manipulated to determine whether, in such
      recording conditions, active electrodes can outperform passive ones. In
      Experiment 2, the performance of active electrodes at the limits of natural skin
      impedance was explored, as was the relationship between active amplification
      circuitry and voltage stability in averaged EOG. RESULTS: Results reveal a
      complex pattern of interrelations between electrode type, impedance, and voltage
      stability, indicating that which type of electrode is "best" depends non
      trivially on the circumstances in which data are being collected. COMPARISON WITH
      EXISTING METHODS: Traditional, passive electrodes acquired the cleanest data
      observed in any of the acquisition conditions at very low impedance, but not at
      any impedance >2 kOmega. CONCLUSION: Active electrodes perform better than
      passive ones at all impedances other than very low ones; however, this is
      qualified by the additional finding that during fast voltage fluctuations, such
      as those most desirable in most ERP studies, active electrodes are less able to
      accurately follow the EEG than passive ones.

PMID- 25075799
TI  - Consistent etiology of severe, frequent psychotic experiences and milder, less
      frequent manifestations: a twin study of specific psychotic experiences in
      adolescence.
AB  - IMPORTANCE: The onset of psychosis is usually preceded by psychotic experiences
      (PE). Little is known about the etiology of PE and whether the degree of genetic
      and environmental influences varies across different levels of severity. A
      recognized challenge is to identify individuals at high risk of developing
      psychotic disorders prior to disease onset. OBJECTIVES: To investigate the degree
      of genetic and environmental influences on specific PE, assessed dimensionally,
      in adolescents in the community and in those who have many, frequent experiences
      (defined using quantitative cutoffs). We also assessed the degree of overlap in
      etiological influences between specific PE. DESIGN, SETTING, AND PARTICIPANTS:
      Structural equation model-fitting, including univariate and bivariate twin
      models, liability threshold models, DeFries-Fulker extremes analysis, and the
      Cherny method, was used to analyze a representative community sample of 5059
      adolescent twin pairs (mean [SD] age, 16.31 [0.68] years) from England and Wales.
      MAIN OUTCOMES AND MEASURES: Psychotic experiences assessed as quantitative traits
      (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, and
      anhedonia, as well as parent-rated negative symptoms). RESULTS: Genetic
      influences were apparent for all PE (15%-59%), with modest shared environment for
      hallucinations and negative symptoms (17%-24%) and significant nonshared
      environment (49%-64%) for the self-rated scales and 17% for parent-rated negative
      symptoms. Three empirical approaches converged to suggest that the etiology in
      extreme-scoring groups (most extreme scoring: 5%, 10%, and 15%) did not differ
      significantly from that of the whole distribution. There was no linear change in
      heritability across the distribution of PE, with the exception of a modest
      increase in heritability for increasing severity of parent-rated negative
      symptoms. Of the PE that showed covariation, this appeared to be due to shared
      genetic influences (bivariate heritabilities, 0.54-0.71). CONCLUSIONS AND
      RELEVANCE: These findings are consistent with the concept of a psychosis
      continuum, suggesting that the same genetic and environmental factors influence
      both extreme, frequent PE and milder, less frequent manifestations in
      adolescents. Individual PE in adolescence, assessed quantitatively, have lower
      heritability estimates and higher estimates of nonshared environment than those
      for the liability to schizophrenia. Heritability varies by type of PE, being
      highest for paranoia and parent-rated negative symptoms and lowest for
      hallucinations.

PMID- 25075802
TI  - Feasibility of two modes of treatment delivery for child anxiety in primary care.
AB  - In this study, we examine the feasibility of cognitive behavior therapy (CBT) for
      children with anxiety in primary care, using two modes of treatment delivery. A
      total of 48 parents and youth (8-13) with anxiety disorders were randomly
      assigned to receive 10-sessions of CBT either delivered by a child anxiety
      specialist in the primary care clinic or implemented by the parent with therapist
      support by telephone (i.e., face-to-face or therapist-supported bibliotherapy).
      Feasibility outcomes including satisfaction, barriers to treatment participation,
      safety, and dropout were assessed. Independent evaluators, blind to treatment
      condition, administered the Anxiety Disorders Interview Schedule for Children
      (ADIS) and the Clinical Global Impression of Improvement (CGI-I) at baseline,
      post-treatment and 3-month follow-up; clinical self-report questionnaires were
      also administered. Findings revealed high satisfaction, low endorsement of
      barriers, low drop out rates, and no adverse events across the two modalities.
      According to the CGI-I, 58.3%-75% of participants were considered responders
      (i.e., much or very much improved) at the various time points. Similar patterns
      were found for remission from "primary anxiety disorder" and "all anxiety
      disorders" as defined by the ADIS. Clinically significant improvement was seen on
      the various parent and child self-report measures of anxiety. Findings suggest
      that both therapy modalities are feasible and associated with significant
      treatment gains in the primary care setting. (clinicaltrials.gov unique
      identifier: NCT00769925). 

PMID- 25075803
TI  - The weight of MMRV-related febrile convulsions among other clinical factors
      contributing to febrile convulsions in children.
AB  - BACKGROUND: It was previously demonstrated that MMRV vaccine causes a higher rate
      of febrile convulsions (FC) compared to the MMR vaccine. Additional risk factors
      for FC include age, familial tendency, day care attendance, viral diseases,
      complications at birth and developmental delay. OBJECTIVE: We evaluated the
      relative and attributable risk of FC for vaccinees' age, ethnicity, low birth
      weight, preterm birth and MMRV vaccination in 10-24 months old children. METHODS:
      Data on medical history and vaccination were extracted from data warehouses of
      Clalit Health Services and Israel's Ministry of Health and linked on an
      individual record level for 90,294 MMR- and 8344 MMRV-vaccinees. A retrospective
      study design was used to reveal the risk factors associated with FC in study
      participants. RESULTS: During the second week after immunization, an elevated
      relative risk of FC was demonstrated in MMRV-recipients (adjusted RR=2.16 (95%CI:
      1.01; 4.64)). However, the cumulative incidence of FC during the entire 40-day
      observation period did not differ between the MMR and MMRV vaccinees. The MMRV
      specific attributable risk of FC was not statistically significant at any point
      of observation period and was exceedingly low compared to other risk factors,
      equaling 5.3 FC cases per 10,000 vaccinees (95%CI: -1.4; 12.2). DISCUSSION: Our
      findings demonstrate that MMRV-associated FC in 10-24 months old contributes very
      marginally to the overall rate of FC in this population. CONCLUSION: Given the
      low number of MMRV-specific FC cases, their transient nature and the benefit of
      vaccination, the overall benefit-risk of the vaccine can be considered
      favourable. Nonetheless, the option of separate immunization with MMR+V should be
      offered to parents, in order to maintain sufficient vaccine uptake in the
      population.

PMID- 25075804
TI  - Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY
      vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open
      label study.
AB  - BACKGROUND: MenACWY-CRM (Menveo(r), Novartis Vaccines, Siena, Italy) is a
      quadrivalent meningococcal conjugate vaccine developed to help prevent invasive
      meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y.
      It is approved within the European Union in persons >2 years of age and in
      persons from 2 months to 55 years of age in the United States, among other
      countries. Little is known about the immunogenicity and safety of this vaccine in
      Taiwanese children >2 years and adolescents. This study assessed the
      immunogenicity and safety of a single injection of MenACWY-CRM vaccine in
      Taiwanese subjects aged 2-18 years old. METHODS: In this phase III, multicentre,
      open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity
      measures were rates of seroresponse (defined as the proportion of subjects with a
      postvaccination hSBA >=1:8 if the prevaccination (baseline) titre was <1:4, or at
      least a fourfold higher hSBA titre than baseline if the prevaccination titre was
      >=1:4), percentages of subjects with serum bactericidal activity (hSBA) >=1:8 for
      serogroups A, C, W and Y and hSBA geometric mean titres (GMTs). Local and
      systemic reactions and all adverse events (AEs) were recorded for 7 days, and
      medically attended AEs for 1 month post-vaccination. RESULTS: Seroresponse rates
      after MenACWY-CRM vaccination at Day 29 for the serogroups A, C, W, and Y were
      83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with
      hSBA >=1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%,
      respectively. GMTs against all serogroups rose by >=7-fold from baseline to Day
      29. The vaccine was well tolerated. CONCLUSIONS: A single dose of MenACWY-CRM
      demonstrated a robust immune response, and an acceptable safety profile in
      Taiwanese children and adolescents.

PMID- 25075805
TI  - Survival analysis of re-treatment after laser refractive corneal surgery in
      patients with myopia.

PMID- 25075806
TI  - Anterior gas breakthrough during femtosecond intrastromal astigmatic keratotomy
      (FISK).

PMID- 25075807
TI  - Differences between the estimated and Scheimpflug image-measured axial
      intraocular lens positions and their relation to refractive error after cataract
      surgery.

PMID- 25075808
TI  - Inclusion of sunflower seed and wheat dried distillers' grains with solubles in a
      red clover silage-based diet enhances steers performance, meat quality and fatty
      acid profiles.
AB  - The current study compared beef production, quality and fatty acid (FA) profiles
      of yearling steers fed a control diet containing 70 : 30 red clover silage (RCS)
      : barley-based concentrate, a diet containing 11% sunflower seed (SS) substituted
      for barley, and diets containing SS with 15% or 30% wheat dried distillers' grain
      with solubles (DDGS). Additions of DDGS were balanced by reductions in RCS and SS
      to maintain crude fat levels in diets. A total of two pens of eight animals were
      fed per diet for an average period of 208 days. Relative to the control diet,
      feeding the SS diet increased (P<0.05) average daily gain, final live weight and
      proportions of total n-6 FA, non-conjugated 18:2 biohydrogenation products (i.e.
      atypical dienes) with the first double bond at carbon 8 or 9 from the carboxyl
      end, conjugated linoleic acid isomers with the first double bond from carbon 7 to
      10 from the carboxyl end, t-18:1 isomers, and reduced (P<0.05) the proportions of
      total n-3 FA, conjugated linolenic acids, branched-chain FA, odd-chain FA and
      16:0. Feeding DDGS-15 and DDGS-30 diets v. the SS diet further increased (P<0.05)
      average daily gains, final live weight, carcass weight, hot dressing percentage,
      fat thickness, rib-eye muscle area, and improved instrumental and sensory panel
      meat tenderness. However, in general feeding DGGS-15 or DDGS-30 diets did not
      change FA proportions relative to feeding the SS diet. Overall, adding SS to a
      RCS-based diet enhanced muscle proportions of 18:2n-6 biohydrogenation products,
      and further substitutions of DDGS in the diet improved beef production, and
      quality while maintaining proportions of potentially functional bioactive FA
      including vaccenic and rumenic acids.

PMID- 25075809
TI  - Talk weight: an observational study of communication about patient weight in
      primary care consultations.
AB  - BACKGROUND: Obesity is a major public health issue and primary care practitioners
      are well placed to opportunistically raise the issue of overweight or obesity
      with their patients. AIM AND METHODS: This study investigated the prevalence of
      weight discussion in primary care consultations with overweight and obese
      patients, in a practice in Fife, Scotland, and described weight-related
      communication using video analysis. FINDINGS: Weight was raised in 25% of
      consultations with overweight and obese patients. GPs initiated weight discussion
      more often than patients; however, these attempts were often blocked by patients.
      Weight-related outcomes were more common when patients initiated the weight
      discussion. This study confirms the potential of video analysis for understanding
      primary care weight discussion. It also suggests that GPs may benefit from a
      communication-based intervention to tackle patient blocking behaviours and
      contributes to the evidence suggesting that interventions targeted to increase
      the prevalence of weight-related discussions with their patients are needed.

PMID- 25075810
TI  - Cutaneous metastases of prostatic small cell neuroendocrine carcinoma.

PMID- 25075811
TI  - Longitudinal changes in awareness over 36 months in patients with mild
      Alzheimer's disease.
AB  - BACKGROUND: Longitudinal changes in awareness in dementia have been studied with
      short follow-up time and mostly in small patient groups (including patients with
      moderate dementia). We investigated awareness in patients with mild Alzheimer's
      disease (AD) over 36 months and studied if a decline in awareness was associated
      with decline in cognition and increase in neuropsychiatric symptoms. METHODS:
      Awareness was measured on a categorical scale in 95 AD patients (age >=50 years,
      Mini-Mental State Examination (MMSE) score >=20). Awareness was rated at three
      time points (follow-up at 12 and 36 months) where MMSE, Neuropsychiatric
      Inventory (NPI-Q), and Cornell scale for Depression in Dementia also were
      applied. RESULTS: At 12 months, 26% had lower awareness rating as compared to
      baseline and at 36 months lower awareness ratings were found in 39%. At both
      visits, 16% had higher awareness rating as compared to baseline. Patients with
      lower awareness at 36 months as compared to baseline had a more rapid increase in
      NPI-Q score (p = 0.002) over 36 months as compared to patients with stable or
      improved awareness over 36 months. A more rapid decline in MMSE score was
      observed for patients with lower awareness at 36 months (as compared to baseline)
      but only when compared to patients in whom awareness improved over time.
      CONCLUSIONS: The results show essentially no clear relationship between cognitive
      decline over three years and awareness. In some cases, awareness remained stable
      or even improved despite significant cognitive decline. In the subgroup where
      awareness declined over time, overall ratings of neuropsychiatric symptoms
      declined more rapidly than in the remaining patients.

PMID- 25075812
TI  - Cost of fall-related hospitalizations among older adults: environmental
      comparisons from the 2011 Texas hospital inpatient discharge data.
AB  - In the United States, 30% of older adults suffer a fall annually with tremendous
      personal and societal burden. Although estimates of national-level costs are
      available, most of these often cited estimates are dated, and less has been
      published about statewide estimates. This article documents fall-related medical
      costs by age, sex, and different geographic regions based on admission status of
      2,937,579 hospital discharges reported in 2011, with special attention to trends
      over time. There were 77,086 fall-related hospitalizations in 2011, of which
      78.4% represent those aged 50 and older. Among this same age group, total fall
      related costs rose to $3.1 billion in 2011, from $1.9 billion in 2007. Those aged
      75 and older experienced the highest cost, while average cost was lower in
      nonmetropolitan areas. Understanding the distribution of fall-related burden
      across groups and rurality allows researchers to identify social and
      environmental circumstances of falls and identify community resources necessary
      to prevent falls.

PMID- 25075813
TI  - Method validation for preparing serum and plasma samples from human blood for
      downstream proteomic, metabolomic, and circulating nucleic acid-based
      applications.
AB  - BACKGROUND: Formal method validation for biospecimen processing in the context of
      accreditation in laboratories and biobanks is lacking. Serum and plasma
      processing protocols were validated for fitness-for-purpose in terms of key
      downstream endpoints, and this article demonstrates methodology for biospecimen
      processing method validation. METHODS: Serum and plasma preparation from human
      blood was optimized for centrifugation conditions with respect to microparticle
      counts. Optimal protocols were validated for methodology and reproducibility in
      terms of acceptance criteria based on microparticle counts, DNA and hemoglobin
      concentration, and metabolomic and proteomic profiles. These parameters were also
      used to evaluate robustness for centrifugation temperature (4 degrees C versus
      room temperature [RT]), deceleration (low, medium, high) and blood stability
      (after a 2-hour delay). RESULTS: Optimal protocols were 10-min centrifugation for
      serum and 20-min for plasma at 2000 g, medium brake, RT. Methodology and
      reproducibility acceptance criteria were met for both protocols except for
      reproducibility of plasma metabolomics. Overall, neither protocol was robust for
      centrifugation at 4 degrees C versus RT. RT gave higher microparticles and free
      DNA yields in serum, and fewer microparticles with less hemolysis in plasma.
      Overall, both protocols were robust for fast, medium, and low deceleration, with
      a medium brake considered optimal. Pre-centrifugation stability after a 2-hour
      delay was seen at both temperatures for hemoglobin concentration and proteomics,
      but not for microparticle counts. CONCLUSIONS: We validated serum and plasma
      collection methods suitable for downstream protein, metabolite, or free nucleic
      acid-based applications. Temperature and pre-centrifugation delay can influence
      analytic results, and laboratories and biobanks should systematically record
      these conditions in the scope of accreditation.

PMID- 25075815
TI  - Veterinary Mobility Act passes Congress.

PMID- 25075816
TI  - Using YouTube to share teaching resources.

PMID- 25075817
TI  - Human-centered veterinary medicine.

PMID- 25075818
TI  - What is your diagnosis? Foreign body.

PMID- 25075819
TI  - Animal behavior case of the month. Fear-related aggression.

PMID- 25075821
TI  - Pathology in practice. Cutaneous and disseminated infection with squirrel fibroma
      virus (SFV).

PMID- 25075820
TI  - Pathology in practice. Coronary band dystrophy with proliferative pododermatitis.

PMID- 25075822
TI  - Magnetic resonance imaging features of Great Danes with and without clinical
      signs of cervical spondylomyelopathy.
AB  - OBJECTIVE: To characterize and compare the MRI morphological features of the
      cervical vertebral column of Great Danes with and without clinical signs of
      cervical spondylomyelopathy (CSM). DESIGN: Prospective cohort study. ANIMALS: 30
      Great Danes (15 clinically normal and 15 CSM-affected). PROCEDURES: All dogs
      underwent MRI of the cervical vertebral column (C2-3 through T1-2). Features
      evaluated included sites of subarachnoid space compression, spinal cord
      compression, or both; degree, cause, and direction of compression; MRI signal
      changes of the spinal cord; articular process (facet) joint characteristics;
      internal vertebral venous plexus visibility; and presence of extradural synovial
      cysts as well as presence and degree of intervertebral disk degeneration and
      foraminal stenosis. RESULTS: Clinically normal and CSM-affected dogs had 11 and
      61 compressive sites, respectively, detected with MRI. All CSM-affected dogs had
      >= 1 site of spinal cord compression. No signal changes were observed in spinal
      cords of normal dogs, whereas 14 sites of hyperintensity were found in 9 CSM
      affected dogs. Foraminal stenosis was present in 11 clinically normal and all CSM
      affected dogs. The number of stenotic foraminal sites was significantly greater
      in the CSM-affected group, and severe stenosis appeared to be more common in this
      group than in the clinically normal group. Significant differences were
      identified between clinically normal and CSM-affected dogs with regard to amount
      of synovial fluid evident, regularity of articular surfaces, degree of articular
      process joint proliferation, and internal vertebral venous plexus visibility.
      CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities were detected with MRI in
      several clinically normal Great Danes. Severe spinal cord compression, number of
      stenotic foraminal sites, and signal changes within the spinal cord distinguished
      CSM-affected from clinically normal Great Danes.

PMID- 25075823
TI  - Efficacy of systemic adjuvant therapies administered to dogs after excision of
      oral malignant melanomas: 151 cases (2001-2012).
AB  - OBJECTIVE: To determine prognostic factors for and compare outcome among dogs
      with oral malignant melanoma following excision with or without various systemic
      adjuvant therapies. DESIGN: Retrospective case series. ANIMALS: 151 dogs with
      naturally occurring oral malignant melanomas treated by excision with or without
      adjuvant therapies from 2001 to 2012. PROCEDURES: Case accrual was solicited from
      Veterinary Society of Surgical Oncology members via an email list service.
      Information collected from case records included signalment, tumor staging, tumor
      characteristics, type of surgical excision, histologic diagnosis, adjuvant
      therapy, and survival time. RESULTS: The overall median survival time was 346
      days. Results of multivariate analysis indicated that tumor size, patient age,
      and intralesional excision (vs marginal, wide, or radical excision) were
      considered poor prognostic indicators. All other demographic and clinical
      variables were not significantly associated with survival time after adjusting
      for the aforementioned 3 variables. A clear survival benefit was not evident with
      any systemic adjuvant therapy, including vaccination against melanoma or
      chemotherapy; however, the number of dogs in each treatment group was small.
      Ninety-eight dogs received no postoperative adjuvant therapy, and there was no
      difference in survival time between dogs that did (335 days) and did not (352
      days) receive systemic adjuvant therapy. CONCLUSIONS AND CLINICAL RELEVANCE: For
      dogs with oral malignant melanoma, increasing tumor size and age were negative
      prognostic factors. Complete excision of all macroscopic tumor burden improved
      survival time. Long-term survival was possible following surgery alone. Although
      systemic adjuvant therapy was not found to improve survival time, this could have
      been due to type II error.

PMID- 25075824
TI  - Clinical signs and outcome of dogs treated medically for degenerative lumbosacral
      stenosis: 98 cases (2004-2012).
AB  - OBJECTIVE: To compare clinical signs of dogs treated medically or surgically for
      degenerative lumbosacral stenosis (DLSS) and assess outcome after medical
      treatment. DESIGN: Retrospective case series. ANIMALS: Client-owned dogs treated
      medically (n = 49) or surgically (49) for DLSS. PROCEDURES: Medical records from
      2004 to 2012 were reviewed. Dogs were included if they had clinical signs,
      clinical examination findings, and MRI abnormalities consistent with DLSS.
      Several variables were compared between surgically and medically treated dogs:
      age, sex, duration of clinical signs, presence or absence of neurologic deficits,
      urinary and fecal incontinence, concurrent medical conditions, and medical
      treatment before referral. Medical treatment after obtaining a final diagnosis of
      DLSS consisted of restricted exercise in combination with anti-inflammatory and
      analgesic drugs. Surgical treatment consisted of dorsal lumbosacral laminectomy.
      Outcome for medically treated dogs was obtained via a standardized questionnaire.
      RESULTS: Neurologic deficits were observed significantly more often in surgically
      treated dogs. Surgically treated dogs had unsuccessful medical treatment before
      referral significantly more often than did medically treated dogs. Thirty-one of
      49 (63.3%) medically treated dogs were available for follow-up evaluation. Of
      these 31 dogs, 17 (55%) were managed successfully, 10 (32.3%) were managed
      unsuccessfully and underwent surgical treatment, 3 (9.7%) were euthanized because
      of progression of clinical signs, and 1 (3.2%) was alive but had an increase in
      severity of clinical signs after medical management. CONCLUSIONS AND CLINICAL
      RELEVANCE: Clinical signs differed in dogs treated medically or surgically for
      DLSS. Medical treatment for dogs with DLSS was associated with a fair prognosis.

PMID- 25075825
TI  - Placement of a caudal vena cava stent for treatment of Budd-Chiari-like syndrome
      in a 4-month-old Ragdoll cat.
AB  - CASE DESCRIPTION: A 16-week-old 1.5-kg (3.3-lb) sexually intact male Ragdoll
      kitten that had a 9-week history of marked modified transudate ascites was
      evaluated. A membranous obstruction of the caudal vena cava at the cranial aspect
      of the liver was identified via CT angiography. CLINICAL FINDINGS: Physical
      examination findings included a markedly distended abdomen and panting. Testing
      for circulating FIV antibody and FeLV antigen, a PCR assay for feline coronavirus
      performed on a sample of peritoneal fluid, and fecal flotation yielded negative
      results. A diagnosis of Budd-Chiari-like syndrome secondary to a membranous
      obstruction of the caudal vena cava was made. TREATMENT AND OUTCOME: The cat was
      anesthetized, and the subhepatic portion of the caudal vena cava was identified
      and accessed via median celiotomy and direct venipuncture. A 6F 8 * 24-mm balloon
      expandable nitinol biliary stent was placed across the stenotic area under
      fluoroscopic guidance. The patient remained free of clinical signs at the last
      follow-up 13 months following the procedure. CLINICAL RELEVANCE: Budd-Chiari-like
      syndrome is a rare phenomenon in veterinary medicine, and congenital
      malformations should be considered in young feline patients with ascites.
      Computed tomography angiography proved to be a helpful adjunctive imaging
      technique to establish a diagnosis in this case. To the authors' knowledge, this
      is the first report of successful treatment of a congenital caudal vena cava
      obstruction by means of stent placement in a juvenile cat.

PMID- 25075826
TI  - Suspected primary hypoparathyroidism in a domestic ferret (Mustela putorius
      furo).
AB  - CASE DESCRIPTION: A 4-year-old castrated male domestic ferret (Mustela putorius
      furo) was examined because of a 3-week history of intermittent seizures, signs of
      depression, hypocalcemia, and hyperphosphatemia. CLINICAL FINDINGS: Plasma
      biochemical analysis confirmed hyperphosphatemia (17.7 mg/dL) and low
      concentrations of total (4.3 mg/dL) and ionized (0.49 mmol/L) calcium. Serum
      parathyroid hormone concentration (2.30 pmol/L) was low or in the low part of the
      reference interval. TREATMENT AND OUTCOME: Calcium gluconate was administered
      (2.0 mg/kg/h [0.9 mg/lb/h], IV), followed by a transition to administration of
      calcium carbonate (53 mg/kg [24.1 mg/lb], PO, q 12 h) and dihydrotachysterol
      (0.02 mg/kg/d [0.009 mg/lb/d], PO). Attitude of the ferret improved and seizures
      ceased as blood calcium concentrations increased. The ferret was reexamined
      because of seizures approximately 1 year after oral maintenance administration of
      dihydrotachysterol and calcium was initiated. The ferret responded well to
      emergency and long-term treatment but then was lost to follow-up monitoring. The
      ferret died approximately 2 years after the initial evaluation and treatment.
      Hypertrophic cardiomyopathy was diagnosed during necropsy, but the parathyroid
      glands could not be identified. CLINICAL RELEVANCE: To the authors' knowledge,
      primary hypoparathyroidism has not previously been reported in a ferret. The
      condition should be considered for ferrets with hypocalcemia and
      hyperphosphatemia without azotemia. Treatment with dihydrotachysterol and oral
      supplementation of calcium appeared to be a viable option for long-term
      management.

PMID- 25075827
TI  - Evaluation of factors associated with work-related injuries to veterinary
      technicians certified in Minnesota.
AB  - OBJECTIVE: To evaluate the magnitude and consequences of work-related injuries
      and associated factors among veterinary technicians certified in Minnesota.
      DESIGN: Cross-sectional survey. SAMPLE: 1,427 certified veterinary technicians
      (CVTs). PROCEDURES: Surveys were used to collect data on demographics, personal
      characteristics, injury occurrences in the 12 months prior to survey completion,
      and injury consequences. Annual injury rates were estimated on the basis of
      demographic and work-related characteristics. Risk of injury associated with
      various factors was estimated by calculation of incidence rate ratios,
      controlling for multiple factors. RESULTS: 465 of 873 eligible CVTs reported
      1,827 injury events (total and bite injury rates, 237 and 78 injuries/100
      persons/y). Primary injury sources were cats and dogs, and most injuries occurred
      during animal restraint or treatment. Self-reported most severe injuries involved
      bites; cuts, lacerations, or scratches; bruises or contusions; and abrasions.
      Injury consequences included treatment and restricted work activity. Risk of work
      related injury was lower for CVTs who worked < 40 h/wk than for those who worked
      >= 40 h/wk. The risk was higher for CVTs working in small animal or mixed mostly
      small animal facilities and lower for those working in mixed large and small
      animal facilities, commercial or industry operations, and government or
      regulatory facilities, compared with CVTs in colleges or universities. Handling 4
      to > 6 (vs < 4) animal species during the 12 months prior to the survey and
      belief that injuries are not preventable were also associated with higher risk of
      injury. CONCLUSIONS AND CLINICAL RELEVANCE: Several factors associated with the
      risk of work-related injury among CVTs were identified. Beyond these risk
      factors, investigation of additional exposures is integral to relevant
      intervention strategies.

PMID- 25075828
TI  - Evaluation of risk and protective factors for work-related bite injuries to
      veterinary technicians certified in Minnesota.
AB  - OBJECTIVE: To identify risk and protective factors for work-related bite injuries
      among veterinary technicians certified in Minnesota. DESIGN: Nested case-control
      study. SAMPLE: 868 certified veterinary technicians (CVTs). PROCEDURES: A
      questionnaire was mailed to CVTs who previously participated in a survey
      regarding work-related injuries and did (cases; 301 surveys sent) or did not
      (controls; 567) report qualifying work-related animal bite injuries in the
      preceding 12 months. Descriptive statistics were summarized. Demographic and work
      related variables for the month preceding the bite injury (for cases) or a
      randomly selected month (controls) were assessed with univariate analysis (489
      CVTs) and multivariate analysis of a subset of 337 CVTs who worked in small or
      mixed mostly small animal facilities. RESULTS: Responses were received from 176
      case and 313 control CVTs. For the subset of 337 CVTs, risk of bite injury was
      higher for those < 25 years of age (OR, 3.82; 95% confidence interval [CI], 1.84
      to 7.94) than for those >= 35 years of age, for those who had worked < 5 years
      (OR, 3.24; 95% CI, 1.63 to 6.45) versus >= 10 years in any veterinary facility,
      and for those who handled >= 5 species/d (OR, 1.99; 95% CI, 1.06 to 3.74) versus
      < 3 species/d. Risk was lower for CVTs who handled < 10 versus >= 20 animals/d
      (OR, 0.23; 95% CI, 0.08 to 0.71). CONCLUSIONS AND CLINICAL RELEVANCE: Several
      work-related factors were associated with the risk of work-related bite injury to
      CVTs. These findings may serve as a basis for development of intervention efforts
      and future research regarding work-related injuries among veterinary staff.

PMID- 25075829
TI  - GM in the media.

PMID- 25075830
TI  - When 'hacktivists' target your hospital.

PMID- 25075831
TI  - Cybersecurity in health care.

PMID- 25075832
TI  - The origins of antimalarial-drug resistance.

PMID- 25075833
TI  - Spiroindolone KAE609 for falciparum and vivax malaria.
AB  - BACKGROUND: KAE609 (cipargamin; formerly NITD609, Novartis Institute for Tropical
      Diseases) is a new synthetic antimalarial spiroindolone analogue with potent,
      dose-dependent antimalarial activity against asexual and sexual stages of
      Plasmodium falciparum. METHODS: We conducted a phase 2, open-label study at three
      centers in Thailand to assess the antimalarial efficacy, safety, and adverse
      event profile of KAE609, at a dose of 30 mg per day for 3 days, in two sequential
      cohorts of adults with uncomplicated P. vivax malaria (10 patients) or P.
      falciparum malaria (11). The primary end point was the parasite clearance time.
      RESULTS: The median parasite clearance time was 12 hours in each cohort
      (interquartile range, 8 to 16 hours in patients with P. vivax malaria and 10 to
      16 hours in those with P. falciparum malaria). The median half-lives for parasite
      clearance were 0.95 hours (range, 0.68 to 2.01; interquartile range, 0.85 to
      1.14) in the patients with P. vivax malaria and 0.90 hours (range, 0.68 to 1.64;
      interquartile range, 0.78 to 1.07) in those with P. falciparum malaria. By
      comparison, only 19 of 5076 patients with P. falciparum malaria (<1%) who were
      treated with oral artesunate in Southeast Asia had a parasite clearance half-life
      of less than 1 hour. Adverse events were reported in 14 patients (67%), with
      nausea being the most common. The adverse events were generally mild and did not
      lead to any discontinuations of the drug. The mean terminal half-life for the
      elimination of KAE609 was 20.8 hours (range, 11.3 to 37.6), supporting a once
      daily oral dosing regimen. CONCLUSIONS: KAE609, at dose of 30 mg daily for 3
      days, cleared parasitemia rapidly in adults with uncomplicated P. vivax or P.
      falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number,
      NCT01524341.).

PMID- 25075834
TI  - Spread of artemisinin resistance in Plasmodium falciparum malaria.
AB  - BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in
      Southeast Asia and now poses a threat to the control and elimination of malaria.
      Mapping the geographic extent of resistance is essential for planning containment
      and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled
      1241 adults and children with acute, uncomplicated falciparum malaria in an open
      label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients
      received artesunate, administered orally at a daily dose of either 2 mg per
      kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a
      standard 3-day course of artemisinin-based combination therapy. Parasite counts
      in peripheral-blood samples were measured every 6 hours, and the parasite
      clearance half-lives were determined. RESULTS: The median parasite clearance half
      lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at
      the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half
      life >5 hours), strongly associated with single point mutations in the
      "propeller" region of the P. falciparum kelch protein gene on chromosome 13
      (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam
      to central Myanmar. The incidence of pretreatment and post-treatment
      gametocytemia was higher among patients with slow parasite clearance, suggesting
      greater potential for transmission. In western Cambodia, where artemisinin-based
      combination therapies are failing, the 6-day course of antimalarial therapy was
      associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at
      42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now
      prevalent across mainland Southeast Asia, is associated with mutations in
      kelch13. Prolonged courses of artemisinin-based combination therapies are
      currently efficacious in areas where standard 3-day treatments are failing.
      (Funded by the U.K. Department of International Development and others;
      ClinicalTrials.gov number, NCT01350856.).

PMID- 25075836
TI  - Brain abscess.

PMID- 25075835
TI  - Transplantation outcomes for severe combined immunodeficiency, 2000-2009.
AB  - BACKGROUND: The Primary Immune Deficiency Treatment Consortium was formed to
      analyze the results of hematopoietic-cell transplantation in children with severe
      combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors
      associated with a good transplantation outcome need to be identified in order to
      design safer and more effective curative therapy, particularly for children with
      SCID diagnosed at birth. METHODS: We collected data retrospectively from 240
      infants with SCID who had received transplants at 25 centers during a 10-year
      period (2000 through 2009). RESULTS: Survival at 5 years, freedom from
      immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely
      among recipients of grafts from matched sibling donors than among recipients of
      grafts from alternative donors. However, the survival rate was high regardless of
      donor type among infants who received transplants at 3.5 months of age or younger
      (94%) and among older infants without prior infection (90%) or with infection
      that had resolved (82%). Among actively infected infants without a matched
      sibling donor, survival was best among recipients of haploidentical T-cell
      depleted transplants in the absence of any pretransplantation conditioning. Among
      survivors, reduced-intensity or myeloablative pretransplantation conditioning was
      associated with an increased likelihood of a CD3+ T-cell count of more than 1000
      per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery
      but did not significantly affect CD4+ T-cell recovery or recovery of
      phytohemagglutinin-induced T-cell proliferation. The genetic subtype of SCID
      affected the quality of CD3+ T-cell recovery but not survival. CONCLUSIONS:
      Transplants from donors other than matched siblings were associated with
      excellent survival among infants with SCID identified before the onset of
      infection. All available graft sources are expected to lead to excellent survival
      among asymptomatic infants. (Funded by the National Institute of Allergy and
      Infectious Diseases and others.).

PMID- 25075837
TI  - Scorpion envenomation.

PMID- 25075838
TI  - Images in clinical medicine. Heterotopic ossification of a midline abdominal
      incision.

PMID- 25075839
TI  - Case records of the Massachusetts General Hospital. Case 24-2014. A 27-year-old
      man with severe osteoporosis and multiple bone fractures.

PMID- 25075840
TI  - Treatment of malaria--a continuing challenge.

PMID- 25075842
TI  - Survival with cardiac-resynchronization therapy.

PMID- 25075843
TI  - Survival with cardiac-resynchronization therapy.

PMID- 25075844
TI  - Mutant ADA2 in vasculopathies.

PMID- 25075845
TI  - Mutant ADA2 in vasculopathies.

PMID- 25075846
TI  - Mutant ADA2 in vasculopathies.

PMID- 25075847
TI  - Mutant ADA2 in vasculopathies.

PMID- 25075848
TI  - Mutant ADA2 in vasculopathies.

PMID- 25075849
TI  - Parasite burden and severity of malaria in Tanzanian children.

PMID- 25075850
TI  - Parasite burden and severity of malaria in Tanzanian children.

PMID- 25075851
TI  - More on hepatitis B virus rtI233V mutation and resistance to adefovir.

PMID- 25075852
TI  - More on hepatitis B virus rtI233V mutation and resistance to adefovir.

PMID- 25075853
TI  - Dihydroartemisinin-piperaquine failure in Cambodia.

PMID- 25075854
TI  - Images in clinical medicine. Tongue fasciculations in amyotrophic lateral
      sclerosis.

PMID- 25075855
TI  - Hell is other people? Gender and interactions with strangers in the workplace
      influence a person's risk of depression.
AB  - We suggest that interactions with strangers at work influence the likelihood of
      depressive disorders, as they serve as an environmental stressor, which are a
      necessary condition for the onset of depression according to diathesis-stress
      models of depression. We examined a large dataset (N = 76,563 in K = 196
      occupations) from the German pension insurance program and the Occupational
      Information Network dataset on occupational characteristics. We used a multilevel
      framework with individuals and occupations as levels of analysis. We found that
      occupational environments influence employees' risks of depression. In line with
      the quotation that 'hell is other people' frequent conflictual contacts were
      related to greater likelihoods of depression in both males and females (OR =
      1.14, p<.05). However, interactions with the public were related to greater
      likelihoods of depression for males but lower likelihoods of depression for
      females (ORintercation = 1.21, p<.01). We theorize that some occupations may
      involve interpersonal experiences with negative emotional tones that make
      functional coping difficult and increase the risk of depression. In other
      occupations, these experiences have neutral tones and allow for functional coping
      strategies. Functional strategies are more often found in women than in men. 

PMID- 25075856
TI  - Conditioning increases the gain of contraction-induced sarcolemmal substrate
      transport in ultra-endurance racing sled dogs.
AB  - Endurance exercise relies on transsarcolemmal flux of substrates in order to
      avoid depletion of intramuscular reserves. Previous studies of endurance trained
      sled dogs have shown a remarkable capacity of these dogs to adapt rapidly to
      endurance exercise by decreasing the utilization of intramuscular reserves. The
      current study tested the hypothesis that the dogs' glycogen-sparing phenotype is
      due to increased sarcolemmal transport of glucose and fatty acids. Basal and
      exercise-induced transport of glucose and fatty acids into sarcolemmal vesicles
      was evaluated in racing sled dogs prior to and after 7 months of exercise
      conditioning. Sarcolemmal substrate transport capacity was measured using
      sarcolemmal vesicles and radiolabelled substrates, and transporter abundance was
      measured using Western blot quantification in whole muscle homogenates and the
      sarcolemmal vesicle preparations. Conditioning resulted in increased basal and
      exercise-induced transport of both glucose and palmitate. Neither acute exercise
      nor conditioning resulted in changes in muscle content of GLUT4 or FAT/CD36, but
      conditioning did result in decreased abundance of both transporters in the
      sarcolemmal vesicles used for the basal transport assays, and this decrease was
      further amplified in the vesicles used for the exercise-induced transport assays.
      These results demonstrate conditioning-induced increases in sarcolemmal transport
      of oxidizable substrates, as well as increased gain of exercise-induced
      sarcolemmal transport of these substrates. These results further indicate that
      increased sarcolemmal transport of oxidizable substrates may be due to either an
      increased intrinsic capacity of the existing transporters or to a different
      population of transporters from those investigated. 

PMID- 25075857
TI  - In vitro cytotoxicity of some Narcissus plants extracts.
AB  - This study compares the chloroform extracts of bulbs and roots of Narcissus
      papyraceus Ker Gawl. and Narcissus tazetta L. The cytotoxicity of the plant
      extracts was evaluated against human hepatocellular carcinoma cell line (HEPG2)
      and colon carcinoma cell line (HCT116) in comparison to doxorubicin. The extracts
      from the after-flowering (AF) bulbs of N. tazetta L. and N. papyraceus exhibited
      strong cytotoxic activity against HEPG2 (IC50: 2.2, 3.5 MUg mL(-1)) and HCT116
      (IC50: 4.2, 3.9 MUg mL(-1)) cell lines, respectively. N. tazetta L. bulbs
      exhibited the least cell viability percentage in HepG-2 cell line (5.32%), while
      the AF root extracts of N. papyraceus exhibited the least cell viability
      percentage in HCT116 cell line (4.93%), when applied at a concentration of 50 MUg
      mL(-1), thereby being more active than doxorubicin at the same concentration.

PMID- 25075858
TI  - N-alpha-acetylation of alpha-synuclein increases its helical folding propensity,
      GM1 binding specificity and resistance to aggregation.
AB  - A switch in the conformational properties of alpha-synuclein (alphaS) is
      hypothesized to be a key step in the pathogenic mechanism of Parkinson's disease
      (PD). Whereas the beta-sheet-rich state of alphaS has long been associated with
      its pathological aggregation in PD, a partially alpha-helical state was found to
      be related to physiological lipid binding; this suggests a potential role of the
      alpha-helical state in controlling synaptic vesicle cycling and resistance to
      beta-sheet rich aggregation. N-terminal acetylation is the predominant post
      translational modification of mammalian alphaS. Using circular dichroism,
      isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed
      the effects of N-terminal acetylation on the propensity of recombinant human
      alphaS to form the two conformational states in interaction with lipid membranes.
      Small unilamellar vesicles of negatively charged lipids served as model
      membranes. Consistent with previous NMR studies using phosphatidylserine, we
      found that membrane-induced alpha-helical folding was enhanced by N-terminal
      acetylation and that greater exothermic heat could be measured upon vesicle
      binding of the modified protein. Interestingly, the folding and lipid binding
      enhancements with phosphatidylserine in vitro were weak when compared to that of
      alphaS with GM1, a lipid enriched in presynaptic membranes. The resultant
      increase in helical folding propensity of N-acetylated alphaS enhanced its
      resistance to aggregation. Our findings demonstrate the significance of the
      extreme N-terminus for folding nucleation, for relative GM1 specificity of alphaS
      membrane interaction, and for a protective function of N-terminal-acetylation
      against alphaS aggregation mediated by GM1. 

PMID- 25075859
TI  - Perspectives in pediatric pathology, chapter 3. Testicular development from birth
      to puberty: systematic evaluation of the prepubertal testis.

PMID- 25075860
TI  - Analysis of transcription factor network underlying 3T3-L1 adipocyte
      differentiation.
AB  - Lipid accumulation in adipocytes reflects a balance between enzymatic pathways
      leading to the formation and breakdown of esterified lipids, primarily
      triglycerides. This balance is extremely important, as both high and low lipid
      levels in adipocytes can have deleterious consequences. The enzymes responsible
      for lipid synthesis and breakdown (lipogenesis and lipolysis, respectively) are
      regulated through the coordinated actions of several transcription factors (TFs).
      In this study, we examined the dynamics of several key transcription factors
      (TFs) - PPARgamma, C/EBPbeta, CREB, NFAT, FoxO1, and SREBP-1c - during adipogenic
      differentiation (week 1) and ensuing lipid accumulation. The activation profiles
      of these TFs at different times following induction of adipogenic differentiation
      were quantified using 3T3-L1 reporter cell lines constructed to secrete the
      Gaussia luciferase enzyme upon binding of a TF to its DNA binding element. The
      dynamics of the TFs was also modeled using a combination of logical gates and
      ordinary differential equations, where the logical gates were used to explore
      different combinations of activating inputs for PPARgamma, C/EBPbeta, and SREBP
      1c. Comparisons of the experimental profiles and model simulations suggest that
      SREBP-1c could be independently activated by either insulin or PPARgamma, whereas
      PPARgamma activation required both C/EBPbeta as well as a putative ligand.
      Parameter estimation and sensitivity analysis indicate that feedback activation
      of SREBP-1c by PPARgamma is negligible in comparison to activation of SREBP-1c by
      insulin. On the other hand, the production of an activating ligand could
      quantitatively contribute to a sustained elevation in PPARgamma activity. 

PMID- 25075863
TI  - Patterns in acute otitis media drug prescriptions: a survey of Italian
      pediatricians and otolaryngologists.
AB  - OBJECTIVE: To evaluate whether physicians follow current guidelines for managing
      acute otitis media (AOM) and whether educational programs are needed to improve
      knowledge of AOM treatment among paediatricians (PEDs) and otolaryngologists
      (ENTs) Methods: A total of 1270 PEDs and 852 ENTs were randomly selected and
      interviewed with an anonymous questionnaire about how they managed AOM. RESULTS:
      Inappropriate AOM approaches were identified among 60.2% of PEDs and 88.5% of
      ENTs (p < 0.001). Amoxicillin and amoxicillin with clavulanic acid were
      appropriately chosen as first-line drugs by the majority of PEDs and ENTs,
      although significantly more ENTs reported otherwise (15.8% PEDs vs 25.5% ENTs; p
      < 0.001). ENTs were significantly more likely than PEDs to report prescribing
      decongestants, mucolytics, anti-inflammatory drugs, and steroids (p < 0.001).
      CONCLUSION: These results show that AOM prescriptions for antibiotics and
      adjunctive treatments are often inappropriate and highlight the need for
      educational strategies aimed at PEDs and ENTs to improve their compliance with
      evidence-based guidelines for AOM treatment.

PMID- 25075862
TI  - Rational modification of estrogen receptor by combination of computational and
      experimental analysis.
AB  - In this manuscript, we modulate the binding properties of estrogen receptor
      protein by rationally modifying the amino acid composition of its ligand binding
      domain. By combining sequence alignment and structural analysis of known estrogen
      receptor-ligand complexes with computational analysis, we were able to predict
      estrogen receptor mutants with altered binding properties. These predictions were
      experimentally confirmed by producing single point variants with up to an order
      of magnitude increased binding affinity towards some estrogen disrupting
      chemicals and reaching an half maximal inhibitory concentration (IC50) value of 2
      nM for the 17alpha-ethinylestradiol ligand. Due to increased affinity and
      stability, utilizing such mutated estrogen receptor instead of the wild type as
      bio-recognition element would be beneficial in an assay or biosensor. 

PMID- 25075864
TI  - Synergistic effect of fadrozole and insulin-like growth factor-I on female-to
      male sex reversal and body weight of broiler chicks.
AB  - The aim of this study was to investigate the effects of Fadrozole hydrochloride
      and recombinant human insulin-like growth factor I (rhIGF-I) on female-to-male
      sex reversal, hatching traits, and body weight of broiler chickens. On the third
      day of incubation, fertile eggs were randomly assigned to five experimental
      groups comprising (i) Fadrozole (0.1 mg/egg), (ii) rhIGF-I (100 ng/egg), (iii)
      Fadrozole (0.1 mg/egg) + rhIGF-I (100 ng/egg), (iv) vehicle injection (10 mM
      acetic acid and 0.1% BSA), and (v) non-injected eggs. Eggs in the rhIGF-I
      injected groups showed the mode of hatching time at the 480th hour of incubation,
      12 hours earlier compared to the other groups, with no statistically significant
      difference in mortality and hatchability. On Day 1 and 42 of production, 90% of
      genetically female chicks were masculinized using Fadrozole treatment, while 100%
      female-to-male phenotypic sex reversal was observed in the Fadrozole+rhIGF-I
      group. Fadrozole equalized the body weight of both genders, although rhIGF-I was
      effective on the body weight of male chicks only. Interestingly, combined rhIGF-I
      and Fadrozole could increase the body weight in both sexes compared to the
      individual injections (P<0.05). These findings revealed that (i) IGF-I-treated
      chicken embryos were shown to be an effective option for overcoming the very long
      chicken deprivation period, (ii) the simultaneous treatment with Fadrozole and
      IGF-I could maximize the female-to-male sex reversal chance, (iii) the increase
      in the body weight of masculinized chickens via Fadrozole could be equal to their
      genetically male counterparts, and (iv) the IGF-I effectiveness, specifically
      along with the application of aromatase inhibitors in female chicks, indicates
      that estrogen synthesis could be a stumbling block for the IGF-I action mechanism
      in female embryos. 

PMID- 25075865
TI  - Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with
      caffeine consumption.
AB  - Two genetic loci, one in the cytochrome P450 1A1 (CYP1A1) and 1A2 (CYP1A2) gene
      region (rs2472297) and one near the aryl-hydrocarbon receptor (AHR) gene
      (rs6968865), have been associated with habitual caffeine consumption. We sought
      to establish whether a more refined and comprehensive assessment of caffeine
      consumption would provide stronger evidence of association, and whether a
      combined allelic score comprising these two variants would further strengthen the
      association. We used data from between 4,460 and 7,520 women in the Avon
      Longitudinal Study of Parents and Children, a longitudinal birth cohort based in
      the United Kingdom. Self-report data on coffee, tea and cola consumption
      (including consumption of decaffeinated drinks) were available at multiple time
      points. Both genotypes were individually associated with total caffeine
      consumption, and with coffee and tea consumption. There was no association with
      cola consumption, possibly due to low levels of consumption in this sample. There
      was also no association with measures of decaffeinated drink consumption,
      indicating that the observed association is most likely mediated via caffeine.
      The association was strengthened when a combined allelic score was used,
      accounting for up to 1.28% of phenotypic variance. This was not associated with
      potential confounders of observational association. A combined allelic score
      accounts for sufficient phenotypic variance in caffeine consumption that this may
      be useful in Mendelian randomization studies. Future studies may therefore be
      able to use this combined allelic score to explore causal effects of habitual
      caffeine consumption on health outcomes. 

PMID- 25075866
TI  - Immunomodulatory effect of a wild blueberry anthocyanin-rich extract in human
      Caco-2 intestinal cells.
AB  - Intestinal inflammation is a natural process crucial for the maintenance of gut
      functioning. However, abnormal or prolonged inflammatory responses may lead to
      the onset of chronic degenerative diseases, typically treated by means of
      pharmacological interventions. Dietary strategies for the prevention of
      inflammation are a safer alternative to pharmacotherapy. Anthocyanins and other
      polyphenols have been documented to display anti-inflammatory activity. In the
      present study, three bioactive fractions (anthocyanin, phenolic, and water
      soluble fractions) were extracted from a wild blueberry powder. The Caco-2
      intestinal model was used to test the immunomodulatory effect of the above
      fractions. Only the anthocyanin-rich fraction reduced the activation of NF
      kappaB, induced by IL-1beta in intestinal epithelial Caco-2 cells. Specifically,
      concentrations of 50 and 100 MUg mL(-1) decreased NF-kappaB activation by 68.9
      and 85.2%, respectively (p <= 0.05). These preliminary results provide further
      support for the role of food bioactives as potential dietary anti-inflammatory
      agents. 

PMID- 25075867
TI  - Prognostic value of a quantitative analysis of lipoarabinomannan in urine from
      patients with HIV-associated tuberculosis.
AB  - BACKGROUND: Detection of the mycobacterial cell wall antigen lipoarabinomannan
      (LAM) in urine can be used to diagnose HIV-associated tuberculosis (TB) using a
      qualitative (positive/negative) read-out. However, it is not known whether the
      quantity of LAM present in urine provides additional prognostic information.
      METHODS/FINDINGS: Consecutively recruited adult outpatients initiating
      antiretroviral therapy (ART) in South Africa were investigated for TB regardless
      of clinical symptoms using sputum smear microscopy and liquid culture (reference
      standard). Urine samples were tested using the Clearview TB-ELISA for LAM and the
      Xpert MTB/RIF assay. The ELISA optical densities (OD) were used as a quantitative
      assessment of urine LAM. Among 514 patients with complete sputum and urine LAM OD
      results, culture-confirmed TB was diagnosed in 84 patients. Twenty-three (27.3%)
      were LAM-positive with a median LAM OD of 0.68 (IQR 0.16-2.43; range, 0.10-3.29)
      and 61 (72.6%) were LAM negative (LAM OD <0.1 above background). Higher LAM ODs
      were associated with a range of prognostic indices, including lower CD4 cell
      counts, lower haemoglobin levels, higher blood neutrophil counts and higher
      mycobacterial load as assessed using both sputum and urine samples. The median
      LAM OD among patients who died was more than 6.8-fold higher than that of
      patients who remained alive at 3 months (P<0.001). The small number of deaths,
      however, precluded adequate assessment of mortality risk stratified according to
      urine LAM OD. CONCLUSIONS: In patients with HIV-associated TB, concentrations of
      LAM in urine were strongly associated with a range of poor prognostic
      characteristics known to be associated with mortality risk. Urine LAM assays with
      a semi-quantitative (negative vs. low-positive vs. high-positive) read-out may
      have improved clinical utility over assays with a simple binary result.

PMID- 25075868
TI  - Ultrathin and lightweight 3D free-standing Ni@NiO nanowire membrane electrode for
      a supercapacitor with excellent capacitance retention at high rates.
AB  - A free-standing binder-free 3D Ni@NiO nanowire membrane is fabricated by a simple
      filtration method followed by thermal annealing. With an appropriate annealing
      temperature, the functional nanowires can keep their rough and echinate surface,
      and the conductive network composed of welded nickel nanowire cores is well
      preserved without isolation (0.53 Omega/sq). The unique 3D multigrade mesporous
      structure not only accelerates the intercalation and deintercalation velocity of
      electrolyte ions but also provides numerous electroactive sites for the Faraday
      reaction. As a result, the supercapacitor electrode can preserve a capacitance
      retention of 96.1% (36.9 F/cm(3)) with a high discharge current density,
      indicating its wonderful rate capability. The fabricated membrane electrode
      exhibits high volumetric capacitance, stable cycling life, and remarkable
      retention of the capacitance at high rate, energy, and power density, making it a
      promising candidate for application in portable electronic products. 

PMID- 25075869
TI  - Advances in therapeutics for neurodegenerative tauopathies: moving toward the
      specific targeting of the most toxic tau species.
AB  - Neurodegenerative disease is one of the greatest health concerns today and with
      no effective treatment in sight, it is crucial that researchers find a safe and
      successful therapeutic. While neurofibrillary tangles are considered the primary
      tauopathy hallmark, more evidence continues to come to light to suggest that
      soluble, intermediate tau aggregates--tau oligomers--are the most toxic species
      in disease. These intermediate tau species may also be responsible for the spread
      of pathology, suggesting that oligomeric tau may be the best therapeutic target.
      Here, we summarize results for the modulation of tau by molecular chaperones,
      small molecules and aggregation inhibitors, post-translational modifications,
      immunotherapy, other techniques, and future directions.

PMID- 25075870
TI  - Far-red fluorescence probe for monitoring singlet oxygen during photodynamic
      therapy.
AB  - Singlet oxygen ((1)O2), molecular oxygen in the lowest excited state, has a
      critical role in the cell-killing mechanism of photodynamic therapy (PDT).
      Although (1)O2 phosphorescence measurement has been mainly used to monitor (1)O2
      formation during PDT, its intensity is far insufficient to obtain two-dimensional
      images of intracellular (1)O2 with the subcellular spatial resolution using the
      currently available near-IR detector. Here, we propose a new far-red fluorescence
      probe of (1)O2, namely, Si-DMA, composed of silicon-containing rhodamine and
      anthracene moieties as a chromophore and a (1)O2 reactive site, respectively. In
      the presence of (1)O2, fluorescence of Si-DMA increases 17 times due to
      endoperoxide formation at the anthracene moiety. With the advantage of negligible
      self-oxidation by photoirradiation (PhiDelta < 0.02) and selective mitochondrial
      localization, Si-DMA is particularly suitable for imaging (1)O2 during PDT. Among
      three different intracellular photosensitizers (Sens), Si-DMA could selectively
      detect the (1)O2 that is generated by 5-aminolevulinic acid-derived
      protoporphyrin IX, colocalized with Si-DMA in mitochondria. On the other hand,
      mitochondria-targeted KillerRed and lysosomal porphyrins could not induce
      fluorescence change of Si-DMA. This surprising selectivity of Si-DMA response
      depending on the Sens localization and photosensitization mechanism is caused by
      a limited intracellular (1)O2 diffusion distance (~300 nm) and negligible
      generation of (1)O2 by type-I Sens, respectively. For the first time, we
      successfully visualized (1)O2 generated during PDT with a spatial resolution of a
      single mitochondrial tubule. 

PMID- 25075871
TI  - Metal-free visible-light induced cross-dehydrogenative coupling of tertiary
      amines with diazo compounds.
AB  - The first visible-light induced cross-dehydrogenative coupling between tertiary
      amines and diazo compounds is described. The reaction proceeds smoothly under
      mild and metal-free conditions by using air or O2 as the oxidant, affording
      various beta-amino-alpha-diazo adducts in moderate to good yields with broad
      substrate scopes. The resulting products were successfully employed for the
      synthesis of 4- or 5-ester N-aryl-2,3-dihydrobenzo[d]azepines with high
      regioselectivity simply switched by the selection of the transition metal
      catalysts. 

PMID- 25075873
TI  - Application of the donor-acceptor concept to intercept low oxidation state group
      14 element hydrides using a Wittig reagent as a Lewis base.
AB  - This article outlines our attempts to stabilize the Group 14 element dihydrides,
      GeH2 and SnH2, using commonly employed phosphine and pyridine donors; in each
      case, elemental Ge and Sn extrusion was noted. However, when these phosphorus and
      nitrogen donors were replaced with the ylidic Wittig ligand Ph3P?CMe2, stable
      inorganic methylene complexes (EH2) were obtained, demonstrating the utility of
      this under-explored ligand class in advancing main group element coordination
      chemistry. 

PMID- 25075874
TI  - Deaths: final data for 2007.
AB  - Objectives-This report presents final 2007 data on U.S. deaths, death rates, life
      expectancy, infant and maternal mortality, and trends by selected characteristics
      such as age, sex, Hispanic origin, race, marital status, educational attainment,
      injury at work, state of residence, and cause of death. Methods-Information
      reported on death certificates, which are completed by funeral directors,
      attending physicians, medical examiners, and coroners, is presented in
      descriptive tabulations. The original records are filed in state registration
      offices. Statistical information is compiled in a national database through the
      Vital Statistics Cooperative Program of the Centers for Disease Control and
      Prevention's National Center for Health Statistics. Causes of death are processed
      in accordance with the International Classification of Diseases, Tenth Revision.
      Results-In 2007, a total of 2,423,712 deaths were reported in the United States.
      The age-adjusted death rate was 760.2 deaths per 100,000 standard population, a
      decrease of 2.1 percent from the 2006 rate and a record low historical figure.
      Life expectancy at birth rose 0.2 year, from a 2006 value of 77.7 years to a
      record 77.9 in 2007. Age-specific death rates decreased for most age groups-15
      24, 35-44, 45-54, 55-64, 65-74, 75-84, and 85 and over-and remained unchanged for
      the age groups of under age 1, 1-4, 5-14, and 25-34. The 15 leading causes of
      death in 2007 remained the same as in 2006 with the exception of two causes that
      exchanged ranks. Alzheimer's disease, the seventh leading cause of death in 2006,
      became the sixth leading cause in 2007, and Diabetes mellitus, the sixth leading
      cause in 2006, dropped to the seventh leading cause in 2007. Heart disease and
      cancer continued to be the leading and second-leading causes of death,
      respectively, together accounting for almost one-half of all deaths (48.6
      percent). The infant mortality rate in 2007 was 6.75 deaths per 1,000 live
      births. Conclusions-Mortality patterns in 2007, such as the decline in the age
      adjusted death rate to a record historical low, were generally consistent with
      long-term trends. Life expectancy reached a record high in 2007, increasing 0.2
      year from 2006. 

PMID- 25075875
TI  - Limonoids from the Leaves and Twigs of Walsura yunnanensis.
AB  - Nine new cedrelone limonoids, namely, walsuranolide B (1), 11beta-hydroxy-23-O
      methylwalsuranolide (2), yunnanolide A (3), yunnanol A (4), 11beta
      hydroxyisowalsuranolide (5), 11beta-hydroxy-1,2-dihydroisowalsuranolide (6),
      1alpha,11beta-dihydroxy-1,2-dihydroisowalsuranolide (7), 11beta-hydroxy-1alpha
      methoxy-1,2-dihydroisowalsuranolide (8), and yunnanolide B (9), together with a
      new cycloartane triterpenoid, (24S*,25R*)-cycloartane-3beta,24,25,26-tetrol (10),
      were isolated from the leaves and twigs of Walsura yunnanensis. Their structures
      were elucidated on the basis of spectroscopic analysis and by comparison with
      literature data. Compounds 3 and 5 exhibited potent cytotoxicity against five
      human tumor cell lines with IC50 values in the range 2.2-4.2 MUM. 

PMID- 25075876
TI  - Ethanol, isobutanol, and biohydrocarbons as gasoline components in relation to
      gaseous emissions and particulate matter.
AB  - The exhaust emissions of three cars using different biofuels were explored at a
      temperature of -7  degrees C. The biofuels studied contained both low- and high
      concentration ethanol blends, isobutanol, and biohydrocarbons. A multipoint fuel
      injection car (MPFI), direct-injection spark-ignition car (DISI), and flex-fuel
      car (FFV) represented three different spark-ignition-car technologies. At -7 
      degrees C, substantial emissions were observed for the three cars, and
      differences were found among ethanol, isobutanol, and biohydrocarbons as fuel
      components. For example, E85 resulted in high acetaldehyde, formaldehyde,
      ethanol, ethene, and acetylene emissions when compared to E30 or lower ethanol
      concentrations. Isobutanol-containing fuel showed elevated butyraldehyde,
      methacrolein, and isobutanol emissions. The highest particulate matter (PM)
      emissions, associated polyaromatic hydrocarbon (PAH) and indirect mutagenicity
      emissions were detected with the DISI car. Oxygenated fuels reduced PM emissions
      and associated priority PAH emissions in the DISI car. PM and PAH emissions from
      the MPFI and FFV cars were generally low. A combination of 10% ethanol and
      biohydrocarbon components did not change emissions significantly when compared to
      ethanol-only-containing E10 gasoline. Therefore, a combination of ethanol or
      isobutanol with biohydrocarbon components offers an option to reach high gasoline
      bioenergy content for E10-compatible cars. 

PMID- 25075877
TI  - Identification of bitter peptides in aged cheddar cheese.
AB  - The compounds responsible for the bitter taste of aged "sharp" Cheddar cheese
      were characterized. Sensory-guided fractionation techniques using gel permeation
      chromatography and multi-dimension semi-preparative reversed-phase high
      performance liquid chromatography revealed the presence of multiple bitter
      compounds. The compounds with the highest perceived bitterness intensity were
      identified by tandem mass spectrometry de novo peptide sequencing as GPVRGPFPIIV,
      YQEPVLGPVRGPFPI, MPFPKYPVEP, MAPKHKEMPFPKYPVEPF, and APHGKEMPFPKYPVEPF; all
      originated from beta-casein. Subsequent quantitative liquid chromatography-tandem
      mass spectrometry analysis reported that the concentrations of GPVRGPFPIIV,
      YQEPVLGPVRGPFPI, and MPFPKYPVEP increased during maturation by 28.7-, 3.1-, and
      1.8-fold, respectively. When directly compared to young "mild" Cheddar,
      APHGKEMPFPKYPVEPF was reported only in the sharp Cheddar cheese, whereas the
      concentration of MAPKHKEMPFPKYPVEPF did not change. Further taste re-engineering
      sensory experiments confirmed the importance of the identified peptides to the
      bitterness of sharp Cheddar. The bitter intensity of the aged "sharp" Cheddar
      model (mild Cheddar with equivalent concentrations of the five bitter peptides in
      the sharp sample) was rated as not significantly different from the authentic
      sharp Cheddar cheese. Among the five peptides, GPVRGPFPIIV was reported to be the
      main contributor to the bitterness intensity of sharp Cheddar. Furthermore, a
      difference from control sensory test also confirmed the significance of the
      bitter taste to the overall perception of aged Cheddar flavor. The sharp Cheddar
      model was reported to be significantly more similar to aged "sharp" Cheddar in
      comparison to the young "mild" Cheddar cheese sample. 

PMID- 25075878
TI  - The effect of smoking on prostate cancer survival: a cohort analysis in
      Barcelona.
AB  - The aim of this study was to analyse the effect of smoking on prostate cancer
      specific mortality and all-cause mortality. A retrospective cohort study was
      conducted with 1109 patients with prostate cancer diagnosed from 1992 to 2008,
      identified through the Hospital del Mar Cancer Registry (Barcelona, Spain).
      Information on smoking habits was retrieved from clinical records and patients
      were classified into three categories: never smoker, exsmoker and current smoker.
      Patients were followed up until December 2011. Survival curves were plotted using
      Kaplan-Meier methods. Cox models were used to estimate hazard ratios and 95%
      confidence intervals. Median age at diagnosis was 70.6 years and 16.7% of
      patients had stage IV tumours. During the follow-up period, 466 deaths occurred,
      36.1% of them being specifically due to prostate cancer. The median follow-up
      time of the censored patients was 5.8 years. There was a significant difference
      in disease-specific survival between never smokers, exsmokers and current smokers
      (P=0.0001). Current smokers presented a worse 5-year survival rate (82.9%)
      compared with exsmokers (88.9%) and never smokers (89.6%). In the multivariate
      analysis, after adjusting for age, disease stage, Gleason score and prostate
      specific antigen, the hazard ratio for smokers was 1.80 (95% confidence interval:
      1.04-3.13) compared with never smokers. In the exsmokers group the risk for
      prostate cancer-specific mortality was very similar to that of never smokers.
      However, the statistical difference disappeared when we stratified by stage (I
      III and IV). In conclusion, smoking was identified as an independent and negative
      prognostic factor for prostate cancer-specific and all-cause mortality. These
      findings suggest that smoking-cessation programmes could be beneficial for
      prostate cancer patients. 

PMID- 25075879
TI  - The association of percentage energy from fat and colon cancer risk among members
      of the US military.
AB  - Epidemiologic studies have previously reported an association between high fat
      intake and colon cancer risk. However, findings have generally been inconclusive.
      This study aimed to investigate the association between fat as a percentage of
      energy intake and colon cancer risk. Study subjects included 215 cases and 215
      matched controls identified by the Defense Medical Surveillance System.
      Percentage energy from fat (Pfat) was estimated using a short dietary screener
      developed by the National Cancer Institute for two time periods: the year before
      the first blood draw and the year before colon cancer diagnosis. Conditional
      logistic regression analysis was used to assess the relationship between colon
      cancer risk and Pfat. Odds ratios and 95% confidence intervals (CIs) were
      calculated. Compared with the lowest quartile of Pfat, the adjusted odds of
      having colon cancer were 2.00 (95% CI 0.96-4.18), 2.83 (95% CI 1.41-5.66), and
      3.37 (95% CI 1.58-7.17), respectively, for the second, third, and highest
      quartiles in the year before cancer diagnosis. Similar results were observed for
      Pfat at an earlier time point. Our findings suggest a positive association
      between Pfat and colon cancer in the US military population. 

PMID- 25075880
TI  - Trends in AIDS incidence in individuals aged 50 years or older in the city of Rio
      de Janeiro, Brazil, 1982-2011: an age-period-cohort analysis.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of three temporal
      components of AIDS incidence (i.e., age, period and cohort) on individuals aged
      50 or older living in Niteroi, Rio de Janeiro (Brazil). METHODS: Age-specific
      incidence rates were calculated from 1982-2011. Negative binomial and Poisson
      models were used to analyze the risk of AIDS by age, period and cohort. RESULTS:
      The risk of AIDS in men was 2.45 times higher than in women, regardless of age
      and period (p-value < 0.001). The incidence of AIDS in individuals older than 69
      years was 7-fold lower than in those aged 50-59 years (p-value < 0.001). A
      decreasing trend in AIDS risk was observed from the youngest cohort (>= 1940) to
      the oldest (1910-1919). From 1982 to 2006, we could detect an increasing trend in
      AIDS risk in the population aged 50 years or older. A peak in rates was detected
      in the period from 2002-2006. The incidence rates in 2002-2006 were six times
      higher than those in 1987-1991 (p-value < 0.001), independent of age and sex (p
      value < 0.001). CONCLUSIONS: An increase of AIDS risk in older people was
      detected. This group should not be neglected by public health programs.

PMID- 25075882
TI  - Associations between subjective symptoms and serum immunoglobulin E levels during
      Asian dust events.
AB  - Asian dust is a seasonal meteorological phenomenon caused by the displacement of
      atmospheric pollutants from the Mongolian and Chinese deserts. Although the
      frequency of Asian dust events and atmospheric dust levels have steadily
      increased in the eastern Asia region, the effects on human health remain poorly
      understood. In the present study, the impact of Asian dust on human health was
      determined in terms of allergic reactions. A total of 25 healthy volunteers were
      tested for a relationship between serum immunoglobulin E (IgE) levels and
      subjective symptoms during a 3-day Asian dust event recorded in April 2012. They
      filled daily questionnaires on the severity of nasal, pharyngeal, ocular,
      respiratory, and skin symptoms by a self-administered visual analog scale. Serum
      levels of non-specific IgE and 33 allergen-specific IgE molecules were analyzed.
      Spearman rank-correlation analysis revealed significant positive associations
      between nasal symptom scores and 2 microbial-specific IgE levels (Penicillium and
      Cladosporium). Microbes migrate vast distances during Asian dust events by
      attaching themselves to dust particles. Therefore, some of these symptoms may be
      associated with type 1 allergic reactions to certain type of microbes. 

PMID- 25075883
TI  - Clavicle Lengthening by Distraction Osteogenesis for Congenital Clavicular
      Hypoplasia: Is it a Real Indication?

PMID- 25075881
TI  - Serum lipid profiles, lipid ratios and Chronic Kidney Disease in a Chinese
      population.
AB  - AIM: To examine the association of serum lipids, lipid ratios with Chronic Kidney
      Disease (CKD) in a Chinese population. METHODS: Data were drawn from a cross
      sectional survey in China. CKD was defined as estimated glomerular filtration
      rate (eGFR) < 60 mL/min/1.73m(2) or albuminuria-to-creatinine ratio (ACR) > 30
      mg/g. Multivariable logistic regressions and multivariate regression models were
      used. Serum lipids and lipid ratios included total cholesterol (TC), triglyceride
      (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
      cholesterol (HDL-C), TG/HDL-C ratio, TC/HDL-C ratio and LDL-C/HDL-C ratio.
      RESULTS: In men, only logarithm-transformed (log) TG was associated with CKD. The
      odds ratio (every SD increment) was 1.39 (95% CI 1.03-1.87, P = 0.03). In women,
      none of the serum lipids and lipid ratios was associated with CKD. Using
      multivariate regression models, it was shown that log TG and log TG/HDL-C were
      negatively correlated with eGFR (P < 0.05) in men and LDL-C and log LDL-C/HDL-C
      ratio were correlated with ACR in men. In female subjects, serum TC, log TG, log
      TG/HDL-C and log TC/HDL-C were negatively correlated with eGFR (P < 0.05). All of
      serum lipid profiles and lipid related ratio were not correlated with ACR in
      women. CONCLUSION: Serum TG is the only suitable predictor for CKD in men.
      However, in women, none of serum lipids and lipid ratio can be used as a
      predictor for CKD. Log TG and log TG/HDL-C are negatively correlated with eGFR in
      both genders.

PMID- 25075884
TI  - Congenital band syndrome with pseudarthrosis of the radius and ulna and impending
      vascular compromise: a case report.
AB  - BACKGROUND: Although amniotic band syndrome is relatively rare, reports of
      pseudarthrosis in conjunction with amniotic band syndrome are even rarer, as are
      reports of impending vascular compromise in the neonatal period. Careful serial
      examinations and timely surgical intervention can successfully avoid the
      catastrophic event of limb loss. We report on a case of upper extremity amniotic
      band syndrome with pseudarthrosis of the radius and ulna that was complicated by
      vascular compromise in a neonate. METHODS: Chart and radiographic data for this
      single case were reviewed and reported retrospectively. RESULTS: A 1-day-old
      neonate born at 28 3/7 weeks of gestational age was transferred to our
      institution for increased swelling to the forearm distal to a congenital band
      associated with an underlying radius and ulna pseudarthrosis. Although the
      forearm and hand were soft and viable initially, severe edema and swelling
      occurred after fluid resuscitation, and on the fourth day of life, the patient
      underwent simple band releases at bedside with 2 longitudinal incisions over the
      radius and ulna. Circulation was restored, and the pseudarthrosis healed with no
      further surgical intervention. Successful delayed reconstruction of the band with
      Z-plasties was performed when the baby was 7 months of age. CONCLUSIONS: In this
      case, a relatively simple, straightforward procedure that is familiar to most
      pediatric orthopaedists salvaged a compromised neonatal limb with amniotic band
      syndrome and allowed healing of a pseudarthrosis, allowing more complex
      reconstruction to be performed in a delayed, elective manner. Careful observation
      is necessary in the neonatal period of the baby with a severe band; a viable,
      well-perfused, compressible extremity may still be at risk.

PMID- 25075885
TI  - The safety and efficacy of a transarticular pin for maintaining reduction in
      patients with developmental dislocation of the hip undergoing an open reduction.
AB  - BACKGROUND: Redislocation after an open reduction for develpmental dislocation of
      the hip is relatively common. The purpose of this study was to determine if the
      use of a transarticular pin (TAP) is safe and effective in maintaining reduction.
      METHODS: A total of 578 patients (645 hips) were reviewed after an open
      reduction, mean age at the time of surgery was 2.1 years. In 621 cases a smooth
      Kirschner wire was placed across the joint. The rates of redislocation, avascular
      necrosis (AVN), and other complications were determined. AVN was classified
      according to Kalamchi et al. Outcome was determined at a minimum of 6 years using
      the Severin classification. RESULTS: Redislocation occurred in 27 cases (4.1%
      rate), 24 had a TAP (3.8%) and 3 did not (12.5%). AVN was observed in 127 cases
      (19.7%), it was type I in 73 cases, type II in 38 cases, type III in 14 cases,
      and type IV in 2 cases; AVN was seen in 123 cases which had a TAP (19.8%) and 4
      cases which did not (16.7%). Analyzing pin placement: when it was in the inferior
      third of the neck the rate of AVN was 15.2% (32/211), in the middle third it was
      21.7% (71/326), and in the superior third it was 28.6% (24/84). According to the
      Severin classification for the hips with a TAP, 496 were type I or II (79.8%),
      113 were type III (18.2%), 10 were type IV (1.6%), and 2 were type V (0.3%); in
      the group without a TAP 19 cases were type I or II (79.2%), 4 were type III
      (16.7%), and 1 was type IV. CONCLUSIONS: The use of a TAP was effective in
      maintaining reduction and was not associated with significant morbidity. Placing
      the pin in the inferior third of the neck was associated with the lowest rate of
      AVN. LEVEL OF EVIDENCE: Level IV--therapeutic.

PMID- 25075886
TI  - Direct-beam radiation exposure to surgeons during pinning of supracondylar
      humerus fractures.

PMID- 25075887
TI  - Predicting the need for surgical intervention in patients with idiopathic
      clubfoot.
AB  - BACKGROUND: The purpose of this study was to determine the early factors
      associated with the need for surgical interventions in patients with idiopathic
      clubfoot treated with the Ponseti method. METHODS: All patients with idiopathic
      clubfoot treated with Ponseti method at our institution with >3 years of follow
      up were evaluated. Age at presentation, history of previous treatment, number of
      casts used, need for percutaneous Achilles tenotomy (PAT), age of initiation of
      foot abduction orthosis (FAO), compliance with FAO, and need for additional casts
      were recorded. Dimeglio/Bensahel and Catterall/Piriani scores were recorded at
      initial presentation, at initiation of FAO, at 1, 2, 3 years of follow-up, and at
      the most recent follow-up. RESULTS: Since 2000, 86 patients (134 feet) had >3
      years of follow-up from time of initial presentation, and 43 of these feet (32%)
      had undergone surgery beyond a PAT. Patients who were noncompliant with the FAO
      were 7.9 times more likely to need surgery than those who were compliant
      [confidence interval (CI), 2.8-22.0; P<0.001]. Female patients were 5.4 times
      more likely to need surgery than male patients (CI, 1.8-16.6; P=0.003). For every
      1 point increase in Dimeglio/Bensahel score at presentation, patients were 1.3
      times more likely to need surgery (CI, 1.0-1.5; P=0.033). For every 1 point
      increase in Dimeglio/Bensahel score at initiation of the FAO, patients were 1.5
      times more likely to need surgery (1.1-2.0, P=0.005). Moreover, for each
      additional cast required before the initiation of the FAO, patients were 1.5
      times less likely to need surgery (CI, 1.1-2.7; P=0.030). No other variable
      significantly contributed to predicting the need for surgery. CONCLUSIONS: There
      are early factors that can be used to predict increased risk for surgical
      intervention in patients undergoing treatment for idiopathic clubfoot. Female
      patients and those patients with higher Dimeglio/Bensahel scores at presentation
      and at initiation of the FAO are at increased risk for needing surgical
      intervention. Noncompliance with the FAO is associated with the highest risk for
      surgical intervention. LEVEL OF EVIDENCE: Level III.

PMID- 25075889
TI  - Gait patterns in children with limb length discrepancy.
AB  - BACKGROUND: Very few articles describe the compensations in gait caused by limb
      length discrepancy (LLD). Song and colleagues explored kinematic and kinetic
      variables utilizing work equalization as a marker of successful compensation for
      LLD. They found no difference in strategies based on the location of pathology.
      The purpose of this study was to define the various gait patterns in patients
      with LLD and the impact of these compensations on gait kinetics. METHODS: Forty
      three children (mean age 12.9+/-3.7 y) with LLD >2 cm were evaluated in the
      motion lab using a VICON motion system with 2 AMTI force plates. Etiologies
      included Legg-Calve-Perthes, developmental hip dysplasia, growth plate damage due
      to infection or trauma, congenital shortening of the femur or tibia, and
      syndromes creating shortening of the limb. Evaluation included physical
      examination and 3-dimensional motion data generated using the model described by
      Vicon Clinical Manager (VCM). For data analysis, 3 representative trials were
      processed with the Plug-in Gait lower-body model using the "VCM spline" filter.
      Walking strategies were identified by visual review. A kinematic threshold of 2
      SD away from normal values was used for inclusion in each group. Strategies
      included: (1) pelvic obliquity with the short side lower (<-1.5 degrees); (2)
      flexion of the knee of the longer leg in stance (>5.2 degrees); (3) plantar
      flexion of the ankle on the shorter leg through the gait cycle (<0 degrees); and
      (4) early plantarflexion crossover of the shorter limb (plantarflexion crossover
      occurred before 35% of the gait cycle). Variables were extracted into Excel using
      PECS (Vicon Motion Systems). The mean of the 3 trials was used for analysis.
      Scanograms were used to establish lengths of the femur and the lower leg
      including the foot. The percentage difference for the subject (%LLD) was
      calculated as the leg length between the 2 sides divided by the length of the
      long side. The total mechanical work over the stride was the sum of the positive
      work and the absolute value of the negative work in all planes. Paired t tests
      were used to analyze the work differences between the short limb versus the long
      limb. Unpaired t tests were used to compare between the different groups (short
      tibias, short femurs, and controls). RESULTS: Distribution of single strategies
      for the group included: pelvis (11), equinis (5), vaulting (7), knee flexion (3);
      17 subjects used multiple strategies. If the discrepancy was in the femur,
      patients chose a more distal compensation strategy, utilizing ankle movements,
      which resulted in more work at the ankle joint on the short limb compared with
      normal (P<0.0001). All subjects with tibia shortening showed pelvic obliquity (3
      combined with knee flexion), which caused more work at the hip joint on the short
      limb compared with normal (P<0.01). Total mechanical work on the uninvolved limb
      was above normal for all groups (P<0.0001). CONCLUSIONS: Our study contradicts
      previous literature that found no difference in strategy on the basis of location
      of the shortening and also a higher number of children with pelvic obliquity than
      previously described. It appears that different compensation schemes are used by
      patients with LLD. The increase in work may have long-term implications for
      management. Future studies will include changes in kinematics and work, after
      intervention. Better understanding of postoperative changes from different
      surgical methods may provide more insight for preoperative planning and may lead
      to a more satisfactory outcome for specific patients. LEVEL OF EVIDENCE: Level
      II.

PMID- 25075888
TI  - Pinless halo in the pediatric population: indications and complications.
AB  - BACKGROUND: The use of the conventional halo is accompanied by the possibility of
      serious complications, especially in the pediatric population. Complications
      could include penetration of pin into the skull, pin loosening, pin tract
      infection, cranial nerve palsies, and vest-related pressure sores. The
      noninvasive "pinless" halo was introduced in an attempt to mitigate these
      problems while retaining the effectiveness of the conventional halo. The purpose
      of this study is to determine the indications and complications related to
      pinless halo application. METHODS: We retrospectively reviewed 61 patients, whose
      treatment included the use of a pinless halo device, presenting to our
      institution between 2004 and 2012. RESULTS: There were 35 male and 26 female
      patients with an average age of 6.04 years. Indications of pinless halo
      application included postoperative immobilization for congenital muscular
      torticollis in 38 cases, conservative management of atlantoaxial rotatory
      subluxation in 11 cases, postoperative immobilization following cervical fusion
      in 10 cases, and immobilization for occipital condyle fracture in 2 cases. The
      average duration of the pinless halo application was 32.68 days. Thirteen
      patients had complications, among which major complications were seen in 2
      patients, each of whom developed a pressure sore; one on the scalp and the other
      on the chest. Both the pressure sores responded to local treatment; however, 1
      resulted in permanent alopecia. CONCLUSIONS: The use of the noninvasive pinless
      halo was found to be safe with few complications in our study. The complications
      were infrequent and patients were compliant to treatment, indicating that this
      modality is patient-friendly. Effectiveness of this treatment in comparison with
      invasive halos and other cervical orthoses was not determined and is a limitation
      of this study. LEVEL OF EVIDENCE: Level IV-Case series.

PMID- 25075891
TI  - Cast saw burns: evaluation of simple techniques for reducing the risk of thermal
      injury.
AB  - BACKGROUND: Although a routine practice in all orthopaedic clinics, the use of
      cast saws is not without risk of thermal and abrasive injury to patients. This
      study investigates the use of readily available supplies for reducing oscillating
      saw blade operating temperatures. METHODS: An oscillating cast saw blade and an
      adhesive thermocouple fixed to the blade were uniformly heated and subsequently
      cooled from 70  degrees C to 45  degrees C using 6 different methods. Variables
      tested included the use of water applied with cotton cast padding or gauze
      dressing, 70% isopropyl alcohol applied with cotton cast padding, gauze dressing,
      or commercially available alcohol pads, and ultrasound gel applied with gauze
      dressing. All methods were tested with either the cast saw off or the saw and
      vacuum running. Statistical analysis included a 2-way analysis of variance to
      compare conditions with the cast saw off versus on and Tukey-adjusted pairwise
      comparisons of individual variables within each group. RESULTS: Cast saw blade
      cooling in ambient air required 114.2 seconds, whereas oscillating the blade and
      using the vacuum reduced the time to 14.6 seconds. Applying 70% isopropyl alcohol
      with a commercially available pad or ultrasound gel on a gauze dressing only
      required 9.0 and 10.2 seconds, respectively. Cooling with water or 70% isopropyl
      alcohol applied with either gauze dressing or cotton cast padding ranged from 4.8
      to 7.4 seconds. CONCLUSIONS: At rest, the cast saw blade required almost 2
      minutes to return to safe operating temperatures after being heated to 70 
      degrees C. Running the saw and vacuum resulted in significantly faster cooling
      across all measured variables. Of all methods tested, cooling with 70% isopropyl
      alcohol using gauze or cast padding or cooling with water on gauze resulted in
      the fastest responses. As a result, this study suggests that the routine use of
      any of these 3 methods would significantly decrease the risk of patient
      discomfort and thermal injury during cast cutting. CLINICAL RELEVANCE: Provide
      simple method for decreasing risk of thermal injury when removing casts.

PMID- 25075890
TI  - Are Fassier-Duval rods at risk of migration in patients undergoing spine magnetic
      resonance imaging?
AB  - BACKGROUND: The Fassier-Duval (FD) rod is a stainless-steel device widely used to
      correct bone deformities and reduce the risk of fractures in patients with
      osteogenesis imperfecta (OI). Since these are telescopic expandable rods, there
      has been a reluctance to perform magnetic resonance imaging (MRI) in patients
      with OI secondary to a theoretical risk of migration during the MRI scans. The
      primary aim of this study was to assess the risk of migration of FD rods in
      patients who underwent MRI of the spine. The secondary aims are to assess the
      heating effects and artifact of these implants. METHODS: We retrospectively
      reviewed our database for all patients with OI who had undergone FD rodding and
      subsequent MRI evaluation for craniofacial and spinal disorders. Ten patients
      were eligible to be included in the study. The MRI examination was performed in
      all patients using a1.5 T magnet. The radiographic images pre-MRI and post-MRI
      were evaluated and compared to assess whether or not migration of implants had
      occurred. Patients' charts and MRI logbooks were reviewed to assess the heating
      effects based on patient-reported events during or immediately after the MRI. In
      addition, the scans were reviewed to evaluate peri-implant soft tissues to assess
      for changes that might indicate such effect. Artifact was judged to be present if
      it interfered with the evaluation of any portion of spinal anatomy of clinical
      interest. RESULTS: Ten patients underwent 19 FD roddings. The indications for MRI
      in these patients were basilar invagination, basilar impression, platybasia, and
      complex scoliosis. None of the implants have shown any migration, heating effect,
      or artifact. CONCLUSIONS: FD rods are safe and pose no risk of migration, heating
      effects, or artifact when undergoing an MRI of the spine using a 1.5 T magnet.
      With the introduction of magnet strengths higher than 1.5 T, further testing
      should be performed. LEVEL OF EVIDENCE: Level IV.

PMID- 25075892
TI  - Pronator teres transfer for forearm and wrist deformity in cerebral palsy
      children.
AB  - BACKGROUND: Forearm pronation and wrist flexion contracture can be a disability
      for daily living care and 2-hand function in cerebral palsy (CP) children. It may
      be beneficial to improve their posture and hand-grip power for better functional
      outcome. The purpose of our study was to investigate the outcome of pronator
      transfer in CP children. METHODS: Seventeen spastic CP patients (14 hemiplegic, 3
      diplegic; 14 male, 3 female; mean age, 12 y 5 mo) underwent pronator teres
      transfer for forearm pronation and wrist flexion contractures. The mean follow-up
      period was 46 months. We recorded Gross Motor Function Classification System
      level, modified Ashworth scale, forearm and wrist range of motion, forearm
      resting position, grip power, and 3 basic daily living skills preoperatively and
      postoperatively. Paired t test was used for statistical analysis. RESULTS: The
      average forearm active supination gained 80.9 degrees (P<0.05) and the active
      forearm pronation lost 22 degrees (P<0.05), with average postoperative total
      active forearm range of motion 130.9 degrees (P<0.05). The average active wrist
      extension gained 76.9 degrees (P<0.05) and the active wrist flexion lost 31.8
      degrees (P<0.05). The average grip power gained 4.5 kg (P<0.05). The average
      forearm resting position improved to 10 degrees pronation (P<0.05). The basic
      daily living skills showed great improvement. CONCLUSIONS: Our procedure improved
      the functional outcome in wrist extension and decreased the forearm pronation.
      Therefore, significant grip-strength enhancement and better forearm posture was
      noted. It is an additional armamentarium in the management of upper extremity
      disability in CP children. LEVEL OF EVIDENCE: Level IV-case series.

PMID- 25075893
TI  - Recurrence of equinus foot deformity after tendo-achilles lengthening in patients
      with cerebral palsy.
AB  - BACKGROUND: Recurrence of equinus deformity after surgery is common in patients
      with cerebral palsy. This retrospective study was undertaken to estimate the
      recurrence rate of the equinus deformity after tendo-Achilles lengthening (TAL)
      in patients with cerebral palsy and to investigate the risk factors associated
      with the recurrence. METHODS: Two-hundred forty three ambulatory patients with
      cerebral palsy, who underwent TAL for equinus foot deformity since 1995, and had
      undergone a preoperative and postoperative 3-dimensional gait analysis, were
      included. Cox proportional hazards model was used to determine the significant
      contributing factor for the recurrence of equinus foot deformity. RESULTS: The
      mean patient age at surgery was 7.8+/-2.7 years and the mean follow-up duration
      was 8.1+/-3.4 years. Equinus deformity recurred in 22 of the 243 patients (9.1%)
      and the Kaplan-Meier survival estimate was shown to be 89.4% at 10 years not
      needing repeat surgery. According to the multivariate analysis using the Cox
      proportional hazard model, preoperative ankle dorsiflexion at initial contact
      (P=0.016) was the only significant factor for recurrence of equinus deformity
      after surgery. Age at surgery and the type of limb involvement were not
      associated with the recurrence (P=0.433 and 0.269). The cutoff values of
      preoperative gait kinematics between the nonrecurrence and recurrence groups were
      -19 degrees of ankle dorsiflexion at initial contact (P=0.018). CONCLUSIONS: This
      study showed that the severity of preoperative equinus deformity was a risk
      factor associated with recurrence after TAL in patients with cerebral palsy.
      Therefore, surgeons should consider the recurrence and later revision surgery for
      the patients with severe equinus foot deformity. LEVEL OF EVIDENCE: Therapeutic
      level III.

PMID- 25075894
TI  - Guided growth with the tension band plate construct: a prospective comparison of
      2 methods of implant placement.
AB  - INTRODUCTION: Since its introduction in 2007, the use of 8-plates has gained
      great popularity for the correction of diverse deformities in skeletally immature
      patients. In this study, we evaluate 2 different techniques of implant placement.
      METHODS: A consecutive series of patients with indication of guided growth around
      the knee (femur or tibia) were included in the study. Patients were randomly
      divided in 2 groups, with 8-plate inserted using technique as described by
      Stevens (group A) versus technique modified from Paley (group B). We analyzed
      operative time, radiation exposure, incision size, and intraoperative
      complications. Comparisons between groups were performed with a Mann-Whitney
      test. A 2-tailed P-value <0.05 was considered significant. RESULTS: We evaluated
      a total of 31 procedures in 18 patients (16 in group A and 15 in group B). Age
      and sex was similar in both groups (P=0.470 and 0.720). Operative time and
      radiation exposure was significantly lower in group B: 20 minutes (range, 11.37
      to 29.30 min) versus 13.09 minutes (range, 9.31 to 25 min) (P 0.009), and 0.30
      uGy (range, 0.10 to 1.30 uGy) versus 0.10 uGy (range, 0.00 to 0.70 uGy)
      (P=0.013), respectively. The incision size was also smaller in group B: 27 mm
      (range, 23 to 29 mm) versus 23 mm (range, 18 to 24 mm) (P=0.05). There were no
      intraoperative complications in any of the 2 groups. CONCLUSIONS: Modified
      technique for 8-plate placement seems to reduce operative time, radiation
      exposure, and incision size for guided growth around the knee. STUDY DESIGN:
      Level of evidence II-prospective randomized study.

PMID- 25075895
TI  - Self-growing Instrumentation With Gliding Connectors for Collapsing Spine
      Deformities in Children: A Novel Technique.
AB  - BACKGROUND: The optimal management of young children with neuromuscular spinal
      deformities is currently unknown. A number of spinal instrumentation techniques
      have been proposed in early-onset scoliosis to achieve "guided growth," each with
      its drawbacks. OBJECTIVE: To report a novel self-growing spinal instrumentation
      technique, designed to avoid recurrent surgeries in children with neuromuscular
      disease. METHODS: The technique is based on the control of apical and end
      vertebrae by pedicle screw fixation and limited fusion. Standard 4.5 to 5.5 mm
      side-to-side rod connectors are used as gliding connections. Three children with
      neuromuscular disease underwent the described procedure. The patients were
      followed for an average of 36 months (range, 24 to 60 mo). RESULTS: All patients
      who underwent the procedure showed an average spinal growth of 1.1 mm/year, which
      is comparable with normative growth data and previous reports using growing rods.
      One patient required the exchange of dislodged rods, secondary to the amount of
      growth of the spine. There were no other complications or unplanned surgeries
      during the follow-up period. CONCLUSIONS: This novel method provided growth in a
      group of 3 patients with collapsing neuromuscular spine deformities. LEVEL OF
      EVIDENCE: Level IV-case series.

PMID- 25075896
TI  - Neurological complications after supracondylar femoral osteotomy in cerebral
      palsy.
AB  - BACKGROUND: Knee flexion contracture in children with cerebral palsy (CP) is very
      common and functional impairment leads to a crouch gait. Correction of the knee
      flexion contracture and improvement of the gait pattern by supracondylar femoral
      extension osteotomy seems to be a more effective method than distal hamstring
      procedures in long-standing severe crouch. Only a small number of publications
      reported the neurological complications of this surgical technique. This study
      was planned to identify the risk factors leading to neurological complications
      after supracondylar femoral extension osteotomy in patients with CP. METHODS:
      Supracondylar femoral osteotomies performed for a primary diagnosis of CP with
      rigid knee flexion deformity of 10 to 30 degrees were included in the study.
      Supracondylar femoral extension osteotomy was performed in 28 patients (total: 48
      cases). Neurological complication was not detected in 43 cases (group 1) and
      detected in 5 cases (group 2). Previous surgical operation, concomitant
      operations on the same extremity, application of a brace or long leg cast after
      operation, preoperative and postoperative popliteal angle, amount of correction,
      radiologic correction, tourniquet time, level of malnutrition, and emotional
      state were reviewed. RESULTS: There were 18 boys and 10 girls. The mean age was
      12+/-4 years in group 1 and 13+/-1 years in group 2. Except 6 patients, all
      patients had concomitant operations (38 cases in group 1 and 4 cases in group 2).
      Postoperatively, long leg cast was used in 38 cases and brace in 10 cases. In
      group 1 mean correction was 23+/-3.8 degrees and in group 2 it was 19+/-5.7
      degrees. CONCLUSIONS: Correlation was not found between the incidence of
      neurological complications and amount of correction and deformity. After
      supracondylar femoral extension osteotomy, all patients must be suspected of
      neurological complication, and measures taken to alleviate the stretch at once if
      nerve palsy is diagnosed. LEVEL OF EVIDENCE: Level IV.

PMID- 25075897
TI  - Diagnostic shortcomings of magnetic resonance arthrography to evaluate partial
      rotator cuff tears in adolescents.
AB  - BACKGROUND: Recent evidence suggests an increase in the incidence of partial
      articular-sided rotator cuff tears in adolescent athletes, but the accuracy of
      diagnostic studies has not been previously assessed in this cohort. This study
      was performed to assess the ability of magnetic resonance imaging with
      arthrography (MRIa) to diagnose partial rotator cuff (PRC) pathology in the
      adolescent age group. METHODS: All patients under the age of 19 years who
      underwent shoulder arthroscopy, between August 2008 and August 2010, were grouped
      based on the presence of a PRC tear diagnosed by either MRIa or arthroscopy. The
      control cohort included children without evidence of an intraoperative PRC.
      Surgical findings were then correlated with the preoperative MRIa findings and
      the accuracy of MRIa reading. Interclass coefficient was then determined for the
      MRIa reviewers. RESULTS: Thirty-one of 89 adolescents (mean age, 15.9 y; 36%
      girls and 64% boys) who underwent arthroscopic shoulder surgery were found to
      have radiographic or arthroscopic evidence of a PRC injury. There were 17 boys
      and 14 girls in the PRC group, with a mean age of 15.6 years. The PRC injuries
      involved either the supraspinatus tendon, infraspinatus tendon, or both. MRIa was
      44% sensitive and 87% specific, with a positive predictive value of 64% and a
      negative predictive value of 74% with arthroscopic findings used as the gold
      standard. The ICC between reviewers was kappa=0.57, with an absolute agreement of
      84%. CONCLUSIONS: The overall diagnostic accuracy of the MRIa with regard to
      adolescent PRC injuries was 72%. MRIa was found to be specific, but not sensitive
      for the diagnosis of this pathology. The high false-negative rate seen in this
      adolescent cohort indicates that a PRC injury may be present even with a negative
      MRIa. Therefore, if clinical suspicion indicates a PRC injury, then the treating
      physician should consider management for rotator cuff pathology despite negative
      MRIa findings. LEVEL OF EVIDENCE: Level III--retrospective cohort study.

PMID- 25075898
TI  - Operative versus nonoperative treatment of displaced proximal humeral physeal
      fractures: a matched cohort.
AB  - BACKGROUND: Displaced proximal humeral physeal fractures (PHPF) are rare
      injuries. Because of the lack of comparative studies, treatment has historically
      been based on surgeon preference. The purpose of this study was to compare
      treatment outcomes among skeletally immature patients who underwent operative
      versus nonoperative treatment for Neer-Horwitz (NH) III or IV PHPF. METHODS:
      Skeletally immature patients who underwent treatment for a displaced PHPF from
      2003 to 2012 were identified. Eligible subjects were invited to complete a
      validated shoulder outcome instrument (QuickDASH) and a phone survey. A
      propensity score matching approach was utilized to match subjects who underwent
      operative treatment to subjects who underwent nonoperative treatment on the basis
      of age at injury and NH classification. RESULTS: Seventy patients were identified
      with a NH III or IV PHPF, of whom 32 subjects completed the study. There was also
      no difference (P=0.5637) in the proportion of subjects who developed a less than
      desirable treatment outcome in operative group (57.14%, 4/7) as compared with the
      nonoperative group (42.86%, 3/7). There was also no difference (P=0.5637) in the
      proportion of subjects who developed a less than desirable treatment outcome in
      operative group (57.14%, 4/7) as compared with the nonoperative group.
      Differences in rate of return to preinjury level of activity (P>0.9999), or
      cosmetic appearance scores (P>0.999) were not significantly different. QuickDASH
      scores were 1.9 points (95% CI, 3.0-6.9; P=0.3699) higher overall in the
      nonoperative group as opposed to the operative group. A less than desirable
      treatment outcome was noted in 4/23 (17.4%) subjects who underwent nonoperative
      treatment. Subgroup analysis of the nonoperative cases showed that, for every 1
      year increase in age at initial injury, the odds of less than desirable outcome
      increased by a factor of 3.81 (95% CI, 1.31-21.0). CONCLUSIONS: In a matched
      cohort of patients with proximal humerus physeal fractures, there was no
      difference in occurrence of complications, rate of return to activity, or
      cosmetic satisfaction. Functional outcomes were also nonsignificant, but tended
      to be higher among fractures that underwent nonoperative treatment. Among
      nonoperatively treated fractures, less than desirable outcomes were more common
      in older patients, particularly those older than 12 years of age. LEVEL OF
      EVIDENCE: Level III-therapeutic.

PMID- 25075899
TI  - Does pediatric body mass index affect surgical outcomes of lower-extremity
      external fixation?
AB  - BACKGROUND: Obese patients are highly prevalent in the pediatric orthopaedic
      surgeon's practice and obesity is an increasing issue in the United States.
      Increased body mass index (BMI) has been associated with increased complications
      in pediatric orthopaedic patients, but no study has looked specifically at
      external fixation. The purpose of this study was to determine whether obesity is
      a risk factor for increased complications in lower-extremity procedures requiring
      external fixation. METHODS: A retrospective chart review was conducted of
      pediatric patients who underwent external fixation as definitive operative
      treatment for any condition at a tertiary care hospital over a 15-year period.
      Patients were grouped into normal weight, overweight, and obese based on Centers
      for Disease Control definitions. All orthopaedic complications were recorded.
      RESULTS: A total of 208 patients with a mean age of 11.2 years were identified.
      Ninety-four children were obese at the 95th percentile BMI or higher, 22 were
      overweight and 93 were normal weight. External fixation was applied to the tibia
      in 82 cases, to the femur in 77 and to both in 49. Mean duration of fixation was
      160 days (range, 31 to 570 d) and patients were followed for a mean of 3.9 years
      (range, 1.0 to 12.0 y). There was no statistically significant difference in the
      rate of complications between the 3 groups (P=0.61). In the obese group
      complications occurred in 68.1% versus 66.7% in the overweight group and 61.3% in
      normal weight. CONCLUSIONS: In the setting of external fixator use for lower
      extremity pathology in pediatric patients, there is no association between an
      increase in complications and obesity as defined by BMI. Complication rates are
      high when external fixation is utilized for the lower extremity, however,
      patients and families should not be counseled that increased BMI will add to the
      burden of orthopaedic complications in this situation. LEVEL OF EVIDENCE: Level
      II-prognostic.

PMID- 25075900
TI  - Proper reporting of predictor performance.

PMID- 25075901
TI  - Reply to: "Proper reporting of predictor performance".

PMID- 25075902
TI  - Predictor performance with stratified data and imbalanced classes.

PMID- 25075903
TI  - Improved vectors and genome-wide libraries for CRISPR screening.

PMID- 25075904
TI  - iPipet: sample handling using a tablet.

PMID- 25075905
TI  - Plasmids: shopping in the age of plenty.

PMID- 25075906
TI  - Chromatin biochemistry enters the next generation of code 'seq-ing'.

PMID- 25075908
TI  - Portal venous gas - always an ominous sign?

PMID- 25075907
TI  - Deep mutational scanning: a new style of protein science.
AB  - Mutagenesis provides insight into proteins, but only recently have assays that
      couple genotype to phenotype been used to assess the activities of as many as 1
      million mutant versions of a protein in a single experiment. This approach-'deep
      mutational scanning'-yields large-scale data sets that can reveal intrinsic
      protein properties, protein behavior within cells and the consequences of human
      genetic variation. Deep mutational scanning is transforming the study of
      proteins, but many challenges must be tackled for it to fulfill its promise. 

PMID- 25075909
TI  - Monochorionic Twin Pregnancy Complicated by Right Ventricular Outflow Tract
      Obstruction (RVOTO) of one Fetus without Proof of a Twin-Twin Transfusion
      Syndrome.

PMID- 25075910
TI  - Evaluation of Fetal Weight Estimation Formulas in Assessing Small-for-Gestational
      Age Fetuses.
AB  - PURPOSE: The aim of this study was to compare the accuracy of multiple
      sonographic fetal weight estimation models in assessing small-for-gestational-age
      (SGA) fetuses. MATERIALS AND METHODS: The cohort included all singleton
      pregnancies recorded at a single medical center from January 2004 to September
      2011, with a minimum of 24 weeks of gestation. SGA was defined as a fetal weight
      of less than the 10th percentile. We used birth weight (BW) distribution curves
      for our population, matched according to fetal gender and gestational age.
      Predicted birth weights were calculated using 26 sonographic fetal weight
      estimation models, including targeted formulas for SGA fetuses. RESULTS: 1218
      cases of SGA fetuses that underwent sonographic fetal weight estimation within
      one week prior to delivery were found. Prediction of fetal weight was
      significantly less accurate in SGA fetuses than in the general population. The
      random error for SGA fetuses ranged from 7.2 % to 13.9 % in different models,
      while the systematic error ranged from -12.8 % to 26 %. Most non-targeted
      formulas showed a specificity of over 90 % but a sensitivity of only 20 - 35 % in
      the detection of SGA fetuses, while most targeted formulas had a low specificity
      but a high sensitivity. The model by Scott et al. was found to be the most
      accurate in assessing SGA fetuses in our population. CONCLUSION: Estimation of
      fetal weight in SGA fetuses is less accurate than in the general population. Some
      formulas which are designed for SGA are more accurate than others and their use
      might increase the sensitivity in identifying SGA fetuses, with only a small
      decline in specificity.

PMID- 25075911
TI  - Large structural changes upon protonation of Fe4S4 clusters: the consequences for
      reactivity.
AB  - Density functional calculations reveal that protonation of a MU3-S in [Fe4S4X4](2
      ) clusters (X = halide, thiolate, phenoxide) results in the breaking of one S-Fe
      bond (to >3 A, from 2.3 A). This creates a doubly-bridging SH ligand (MU3-SH is
      not stable), and a unique three-coordinated planar Fe atom. The under
      coordination of this unique Fe atom is the basis of revised mechanisms for the
      acid-catalysed ligand substitution reactions in which substitution of X by PhS
      occurs at the unique Fe site by an indirect pathway involving initial
      displacement of X by acetonitrile (solvent), followed by displacement of
      coordinated acetonitrile by PhSH. When X = Cl or Br the rate of attack by PhSH is
      slower than the dissociation of X(-), and is the rate-determining step; in
      contrast, when X = SEt, SBu(t) or OPh the rate of dissociation of XH is slower
      than attack by PhSH and is rate-determining for these clusters. A full and
      consistent interpretation of all kinetic data is presented including new
      explanations of many of the kinetic observations on the acid-catalysed
      substitution reactions of [Fe4S4X4](2-) clusters. The proposed mechanisms are
      supported by density functional calculations of the structures of intermediates,
      and simulations of some of the steps. These findings are expected to have
      widespread ramifications for the reaction chemistry of both natural and synthetic
      clusters with the {Fe4S4} core. 

PMID- 25075913
TI  - Effect of rapid maxillary expansion on monosymptomatic primary nocturnal
      enuresis.
AB  - OBJECTIVE: To evaluate the effects of rapid maxillary expansion (RME) on
      nocturnal enuresis (NE) related to the nasal airway, nasal breathing, and plasma
      osmolality (as an indicator for antidiuretic hormone). MATERIALS AND METHODS:
      Nineteen patients with monosymptomatic primary NE, aged 6-15 years, were treated
      with RME for 10-15 days. To exclude a placebo effect of the RME appliance, seven
      patients were first treated with a passive appliance. Computed tomography of
      nasal cavity, rhinomanometric, and plasma osmolality measurements were made 2-3
      days before and 2-3 months after the RME period. RME effects on NE were followed
      for three more years. RESULTS: Two to three months after the expansion there were
      significant improvements in the breathing function and a decrease in the plasma
      osmolality. NE decreased significantly in all patients after the RME period, and
      all patients showed full dryness after 3 years. CONCLUSIONS: This study
      demonstrates that RME causes complete dryness in all patients, with significant
      effects on pathophysiological mechanisms related to NE.

PMID- 25075912
TI  - Antidepressants strongly influence the relationship between depression and heart
      rate variability: findings from The Irish Longitudinal Study on Ageing (TILDA).
AB  - BACKGROUND: Heart rate variability (HRV) is known to be reduced in depression;
      however, is unclear whether this is a consequence of the disorder or due to
      antidepressant medication. METHODS: We analysed data on 4750 participants from
      the first wave of The Irish Longitudinal Study on Ageing (TILDA). Time [standard
      deviation of normal to normal intervals (SDNN ms2)] and frequency domain [low
      frequency (LF) and high frequency (HF)] measures of HRV were derived from 3-lead
      surface electrocardiogram records obtained during 10 min of supine rest.
      Depression was assessed using the Center for Epidemiologic Studies - Depression
      scale. RESULTS: Participants on antidepressants [with (n = 80) or without
      depression (n = 185)] differed significantly from controls (not depressed and not
      taking antidepressants n = 4107) on all measures of HRV. Depressed participants
      not taking antidepressants (n = 317) did not differ from controls on any measures
      of HRV. In linear regression analysis adjusted for relevant factors all
      antidepressants were associated with lower measures HRV. Participants on
      selective serotonin reuptake inhibitors (SSRIs) had higher measures of HRV
      relative to participants on tricyclic antidepressants or serotonin-norepinephrine
      reuptake inhibitors respectively. CONCLUSIONS: Our results suggest that
      reductions in HRV observed among depressed older adults are driven by the effects
      of antidepressant medications. SSRIs have less impact on HRV than other
      antidepressants but they are still associated with lower measures of HRV. Study
      limitations include the use of a self-report measure of depression and floor
      effects of age on HRV could have limited our ability to detect an association
      between HRV and depression.

PMID- 25075914
TI  - Redox processes at a nanostructured interface under strong electric fields.
AB  - Manipulation of chemistry and film growth via external electric fields is a
      longstanding goal in surface science. Numerous systems have been predicted to
      show such effects but experimental evidence is sparse. Here we demonstrate in a
      custom-designed UHV apparatus that the application of spatially extended,
      homogeneous, very high (>1 V nm(-1)) DC-fields not only changes the system
      energetics but triggers dynamic processes which become important much before
      static contributions appreciably modify the potential energy landscape. We take a
      well characterized ultrathin NiO film on a Ag(100) support as a proof-of
      principle test case, and show how it gets reduced to supported Ni clusters under
      fields exceeding the threshold of +0.9 V nm(-1). Using an effective model, we
      trace the observed interfacial redox process down to a dissociative electron
      attachment resonant mechanism. The proposed approach can be easily implemented
      and generally applied to a wide range of interfacial systems, thus opening new
      opportunities for the manipulation of film growth and reaction processes at solid
      surfaces under strong external fields. 

PMID- 25075916
TI  - The Goodwin model revisited: Hopf bifurcation, limit-cycle, and periodic
      entrainment.
AB  - The three-variable Goodwin oscillator is a minimal model demonstrating the
      emergence of oscillations in simple biochemical feedback systems. As a
      prototypical oscillator, this model was extensively studied from a theoretical
      point of view and applied to various biological systems, including circadian
      clocks. Here, we reexamine this model, derive analytically the amplitude equation
      near the Hopf bifurcation and investigate the effect of a periodic modulation of
      the oscillator. In particular, we compare the entrainment performance when the
      free oscillator displays either self-sustained or damped oscillations. We discuss
      the results in the context of circadian oscillators. 

PMID- 25075917
TI  - Combined Aphasia and Apraxia of Speech Treatment (CAAST): effects of a novel
      therapy.
AB  - PURPOSE: This investigation was designed to examine the effects of a newly
      developed treatment for aphasia and acquired apraxia of speech (AOS). Combined
      Aphasia and Apraxia of Speech Treatment (CAAST) targets language and speech
      production simultaneously, with treatment techniques derived from Response
      Elaboration Training (Kearns, 1985) and Sound Production Treatment (Wambaugh,
      Kalinyak-Fliszar, West, & Doyle, 1998). The purpose of this study was to
      determine whether CAAST was associated with positive changes in verbal language
      and speech production with speakers with aphasia and AOS. METHOD: Four
      participants with chronic aphasia and AOS received CAAST applied sequentially to
      sets of pictures in the context of multiple baseline designs. CAAST entailed
      elaboration of participant-initiated utterances, with sound production training
      applied as needed to the elaborated productions. The dependent variables were (a)
      production of correct information units (CIUs; Nicholas & Brookshire, 1993) in
      response to experimental picture stimuli, (b) percentage of consonants correct in
      sentence repetition, and (c) speech intelligibility. RESULTS AND CONCLUSIONS:
      CAAST was associated with increased CIU production in trained and untrained
      picture sets for all participants. Gains in sound production accuracy and speech
      intelligibility varied across participants; a modification of CAAST to provide
      additional speech production treatment may be desirable.

PMID- 25075918
TI  - Searching the literature is not for the faint of heart!

PMID- 25075919
TI  - In response to editorial, "writing is not just for other people".

PMID- 25075920
TI  - Changing institutional culture to value human milk.

PMID- 25075921
TI  - The baby-friendly NICU.

PMID- 25075922
TI  - Spotlight on a millennial NANN member and new webinar series.

PMID- 25075923
TI  - Furthering our understanding of the needs of mothers who are pumping breast milk
      for infants in the NICU: an integrative review.
AB  - The purpose of this integrative review was to uncover information regarding
      emotional and other types of support required by mothers providing breast milk
      for infants in the neonatal intensive care unit (NICU). These high-risk infants
      are often unable to directly breastfeed and, thus, mothers need to pump their
      breast milk for weeks to months, which can be both a pleasing experience that
      increases satisfaction and infant involvement, while at the same time being an
      uncomfortable and tiring endeavor. Understanding this notion is important because
      pumping at least 8 times each day is central to increasing or maintaining breast
      milk production. Articles were gathered using PubMed and CINAHL databases. Forty
      four sources were chosen for inclusion in this review. Search terms included
      "breastfeeding," "pumping," "neonatal intensive care unit," "emotional support,"
      and "breast milk." We identified that the emotional and practical support for
      NICU mothers is different from those of other breastfeeding mothers, especially
      around the development of early bonding behaviors. These mothers require
      significant ongoing emotional support from healthcare professionals and their
      partners and peers. Healthcare providers need to monitor breast milk production
      and provide educated encouragement that anticipates breastfeeding challenges,
      especially when the mother is pumping for an extended period of time while their
      infant is maturing in the NICU. Effective providers' support may be best provided
      by selectively bundling interventions to support pumping initiation and
      transition to direct breastfeeding. 

PMID- 25075925
TI  - An ethical case for the provision of human milk in the NICU.
AB  - Despite recommendations from the World Health Organization, the United Nations
      Children's Fund, the American Academy of Pediatrics Section on Breastfeeding, and
      others, only a small percentage of infants in the United States receive exclusive
      human milk for the first 6 months of life. In the United States, decisions
      related to infant feeding are determined by surrogate or proxy in place of the
      neonatal voice, using the "best interest principle" as the guiding ethical focus.
      Given the established research on the benefits of an exclusive human milk diet
      compared with artificial nutrition (infant formula), infant feeding decisions
      made for the critically ill neonate should rest entirely in the infant's best
      interest, not solely in parental authority. If the mother's own milk is not
      available or its use is contraindicated, the American Academy of Pediatrics
      recommends donor human milk. However, the preverbal voice of the neonate makes it
      difficult to isolate the best interest of the infant separated from the family
      unit. Using a case exemplar, it is proposed that the means in which infant
      feeding decisions are made for the critically ill infant should rest entirely in
      the infant's best interest, not parental authority, during the course of care in
      the hospital setting. The best interest principle, surrogate decision making,
      parental authority, and proxy consent are reviewed. Furthermore, a case for the
      best interest principle to further illustrate the importance of the infant's
      voice in relationship to enteral feeding decisions is provided. Finally,
      implications for clinical practice are offered. 

PMID- 25075926
TI  - Characteristics of the NICU work environment associated with breastfeeding
      support.
AB  - PURPOSE: The provision of breastfeeding support in the neonatal intensive care
      unit (NICU) may assist a mother to develop a milk supply for the NICU infant.
      Human milk offers unique benefits and its provision unique challenges in this
      highly vulnerable population. The provision of breastfeeding support in this
      setting has not been studied in a large, multihospital study. We describe the
      frequency of breastfeeding support provided by nurses and examined relationships
      between NICU nursing characteristics, the availability of a lactation consultant
      (LC), and breastfeeding support. SUBJECTS AND DESIGN: This was a secondary
      analysis of 2008 survey data from 6060 registered nurses in 104 NICUs nationally.
      Nurse managers provided data on LCs. These NICUs were members of the Vermont
      Oxford Network, a voluntary quality and safety collaborative. METHODS: Nurses
      reported on the infants (n = 15,233) they cared for on their last shift,
      including whether breastfeeding support was provided to parents. Breastfeeding
      support was measured as a percentage of infants on the unit. The denominator was
      all infants assigned to all nurse respondents on that NICU. The numerator was the
      number of infants that nurses reported providing breastfeeding support. Nurses
      also completed the Practice Environment Scale of the Nursing Work Index (PES
      NWI), a nationally endorsed nursing care performance measure. The NICU nursing
      characteristics include the percentages of nurses with a BSN or higher degree and
      with 5 or more years of NICU experience, an acuity-adjusted staffing ratio, and
      PES-NWI subscale scores. Lactation consultant availability was measured as
      any/none and in full-time equivalent positions per 10 beds. RESULTS: The parents
      of 14% of infants received breastfeeding support from the nurse. Half of the
      NICUs had an LC. Multiple regression analysis showed a significant relationship
      between 2 measures of nurse staffing and breastfeeding support. A 1 SD higher
      acuity-adjusted staffing ratio was associated with a 2% increase in infants
      provided breastfeeding support. A 1 SD higher score on the Staffing and Resource
      Adequacy PES-NWI subscale was associated with a 2% increase in infants provided
      breastfeeding support. There was no association between other NICU nursing
      characteristics or LCs and nurse-provided breastfeeding support. CONCLUSIONS:
      Nurses provide breastfeeding support around the clock. On a typical shift, about
      1 in 7 NICU infants receives breastfeeding support from a nurse. Lactation
      consultants are not routinely available in NICUs, and their presence does not
      influence whether nurses provide breastfeeding support. Better nurse staffing
      fosters nurse provision of breastfeeding support.

PMID- 25075927
TI  - Acceptability and feasibility of a breast milk expression education and support
      intervention in mothers of preterm infants.
AB  - PURPOSE: A pilot study was conducted to assess the acceptability and feasibility
      of a breast milk expression education and support intervention in mothers of
      preterm infants and study procedures. SUBJECTS: Forty mothers of preterm infants
      born at less than 30 weeks of gestation. DESIGN: Pilot randomized controlled
      trial. METHODS: Mothers of preterm infants were randomly allocated to the breast
      milk expression education and support intervention or standard care. The
      experimental intervention encompassed a breast milk expression education session
      on 7 themes, telephone follow-up, and telephone helpline. MAIN OUTCOME MEASURES:
      Data related to the acceptability and feasibility of the intervention and study
      procedures were collected throughout the study. At the end of the study, mothers
      allocated to the experimental intervention completed a self-report questionnaire
      assessing the acceptability of each of the intervention components. RESULTS: It
      was feasible to recruit 70% of eligible mothers and retain 83% of mothers who
      consented to participate in the study. Mothers reported that all the intervention
      components were appropriate and effective in supporting their breast milk
      production. Although the reliability of the data collection method was
      demonstrated, the fidelity of the telephone follow-up faced some challenges.
      CONCLUSIONS: Both the intervention and study procedures were acceptable and
      feasible. Improvements related to the fidelity of the intervention would ensure
      the feasibility and internal validity of a larger-scale trial.

PMID- 25075928
TI  - A designer peptide as a template for growing Au nanoclusters.
AB  - A peptide was designed to generate a sub-nanometric template that guides the
      growth of fluorescent gold nanoclusters. The peptide was endorsed with nucleating
      moieties and a three-dimensional structure that arrests the growth of ultrasmall
      nanoparticles. The nanoclusters are not cytotoxic and can be found in the cytosol
      of cells. 

PMID- 25075929
TI  - High anti-desmoglein 3 antibody ELISA index and negative indirect
      immunofluorescence result in a patient with pemphigus vulgaris in remission:
      evaluation of the antibody profile by newly developed methods.
AB  - IMPORTANCE Pemphigus vulgaris (PV) is a disease that features blistering of the
      skin and mucous membranes caused by autoantibodies directed against desmoglein 3
      (Dsg3) and/or desmoglein 1(Dsg1). Indirect immunofluorescence (IIF) and enzyme
      linked immunosorbent assay (ELISA) are 2 methods that are widely used to measure
      Dsg3 orDsg1 antibody titers in PV. Although the titers of these autoantibodies
      are generally correlated with disease activity, some patients with a high ELISA
      index do not have severe symptoms.We encountered a patient with PV in
      remission,who had a high anti-Dsg3 antibody ELISA index while the IIF result was
      negative.OBSERVATIONS The anti-Dsg3 antibodies of our patient mainly recognized
      Ca2+-dependent conformational epitopes and targeted mature Dsg3 protein.We report
      this case focusing on the discrepancy between ELISA and IIF findings, as well as
      on the specific characteristics of the patient's autoantibodies evaluated by
      newly developed methods.CONCLUSIONS AND RELEVANCE This case emphasizes that a
      discrepancy between disease activity, the ELISA index for Dsg3, and/or IIF
      findings can occur in PV. Further research on similar patients will be required
      to elucidate the pathogenic mechanisms in patients with PV who have nonpathogenic
      antibodies and show a discrepancy between ELISA and IIF.

PMID- 25075930
TI  - Motivational deficits and cognitive test performance in schizophrenia.
AB  - IMPORTANCE: Motivational and cognitive deficits are core features of
      schizophrenia, both closely linked with functional outcomes. Although poor effort
      and decreased motivation are known to affect performance on cognitive tests, the
      extent of this relationship is unclear in patients with schizophrenia. OBJECTIVE:
      To evaluate the association between intrinsic motivation and cognitive test
      performance in patients with schizophrenia. DESIGN, SETTING, AND PARTICIPANTS:
      Cross-sectional and 6-month prospective follow-up study performed at 57 sites in
      the United States, including academic and community medical treatment centers,
      participating in the Clinical Antipsychotic Trials of Intervention Effectiveness
      study. The primary sample included 431 stable patients with a DSM-IV diagnosis of
      schizophrenia currently receiving a stable medication regimen. INTERVENTIONS:
      Cognitive performance and intrinsic motivation were evaluated using a
      comprehensive neuropsychological test battery and a derived measure from the
      Heinrichs-Carpenter Quality of Life Scale, respectively. Symptom severity and
      functional status were also assessed. MAIN OUTCOMES AND MEASURES: The primary
      outcome variable was global neurocognition. Individual domains of cognition were
      also evaluated for their association with motivation. RESULTS: Level of intrinsic
      motivation was significantly and positively correlated with global cognitive test
      performance, a relationship that held for each domain of cognition evaluated
      (correlation range, 0.20-0.34; P < .001). This association was found to be
      reliable after statistically accounting for positive, negative, depressive, and
      overall symptom severity (P < .05) and after accounting for community functioning
      (P < .001). The relationship between motivation and cognitive performance also
      remained significant after controlling for antipsychotic dose (P < .05).
      Prospective increase in motivation during the 6-month follow-up was also found to
      be significantly related to improvement in global cognitive performance (P <
      .05). CONCLUSIONS AND RELEVANCE: The present findings provide strong support for
      a robust and reliable relationship between motivation and cognitive performance
      and suggest that test performance is not purely a measure of ability. Future
      studies assessing cognition in patients with schizophrenia should consider
      potential moderating variables such as effort and motivation. Implications for
      the assessment and interpretation of cognitive impairment based on
      neuropsychological test measures in schizophrenia are discussed, especially in
      the case of clinical trials for cognition-enhancing treatments. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00014001.

PMID- 25075931
TI  - Interfacial reactivity of ruthenium nanoparticles protected by
      ferrocenecarboxylates.
AB  - Stable ruthenium nanoparticles protected by ferrocenecarboxylates (RuFCA) were
      synthesized by thermolytic reduction of RuCl3 in 1,2-propanediol. The resulting
      particles exhibited an average core diameter of 1.22 +/- 0.23 nm, as determined
      by TEM measurements. FTIR and (1)H NMR spectroscopic measurements showed that the
      ligands were bound onto the nanoparticle surface via Ru-O bonds in a bidentate
      configuration. XPS measurements exhibited a rather apparent positive shift of the
      Fe2p binding energy when the ligands were bound on the nanoparticle surface,
      which was ascribed to the formation of highly polarized Ru-O interfacial bonds
      that diminished the electron density of the iron centers. Consistent results were
      obtained in electrochemical measurements where the formal potential of the
      nanoparticle-bound ferrocenyl moieties was found to increase by ca. 120 mV.
      Interestingly, galvanic exchange reactions of the RuFCA nanoparticles with Pd(ii)
      followed by hydrothermal treatment at 200  degrees C led to (partial)
      decarboxylation of the ligands such that the ferrocenyl moieties were now
      directly bonded to the metal surface, as manifested in voltammetric measurements
      that suggested intervalence charge transfer between the nanoparticle-bound
      ferrocene groups. 

PMID- 25075933
TI  - A novel, in vivo, indoor method to preserve rice black-streaked dwarf virus in
      small brown planthopper using wheat seedling as a bridge host.
AB  - Rice black-streaked dwarf virus (RBSDV) naturally infects Gramineae plants
      through small brown planthopper (SBPH) as a vector. However, RBSDV cannot be
      transmitted to the SBPH offspring through transovarian transmission. Wheat plant,
      an important intermediate host in winter, is essential for the completion of the
      annual cycle of RBSDV in farm ecosystem. We developed a novel, in vivo, indoor
      method to preserve RBSDV in SBPH using wheat seedling as a bridge host. The
      temperature range of 23-27 degrees C was initially selected to rear the insects
      and plants. Before initiating the scheme cycle, viruliferous SBPH was obtained by
      feeding the virus-free 1st to 2nd instar nymphs with RBSDV-infected rice plants.
      Four to six RBSDV-infected SBPH were placed per plant to inoculate wheat
      seedlings at two-to-four leaf stages. After 48 h of inoculation, the viruliferous
      SBPH were removed. Five mated, newly emerged virus-free SBPH females were then
      transferred onto each inoculated plant and allowed to lay eggs for 48 h. The
      newly hatched SBPH were raised on wheat seedlings until the 2nd instar nymph
      stage, and then transferred onto healthy rice seedlings for further development
      until 5th instar nymphs or adults. These newly obtained viruliferous SBPH can be
      used for inoculating new wheat seedlings in the succeeding maintenance cycles, or
      for further experiments. We discovered that the incubation period of RBSDV in
      wheat seedlings synchronized with the gestation period of SBPH eggs at four to
      six inoculated viruliferous SBPH per plant and lasted for approximately seven
      days. In addition, this period was optimal for enhancing the SBPH infection ratio
      because SBPH nymphs can only acquire the virus after they hatch. The RBSDV
      infection ratio of the SBPHs acquired through this method consistently exceeded
      50%.

PMID- 25075934
TI  - Discriminatory capacity between HIV-1 and HIV-2 of the new rapid confirmation
      assay Geenius.
AB  - The currently used HIV confirmatory assays, Western blot and line immunoassay,
      are costly, complex and time-consuming. There is a need for cheaper, simpler and
      faster assays for use in high- and low-resource settings. Furthermore, it is
      necessary to differentiate between HIV-1 and HIV-2 infection due to differences
      in disease progression, monitoring and treatment options. Because the new Geenius
      HIV 1/2 Confirmatory Assay (Bio-Rad) has a European Community (CE) label, this
      study focused on its differentiation capacity using serum/plasma specimens from
      established HIV-1, HIV-2 and HIV untypable infections from the AIDS Reference
      Laboratory (ARL) of the Institute of Tropical Medicine (ITM) in Belgium. The
      results were compared with ARL's standard algorithm for diagnosis of HIV
      infection and the new interpretation criteria for discrimination of the INNO-LIA
      HIVI/II Score, Fujirebio, Ghent, Belgium (LIA). The study showed a performance
      comparable to that of the reference LIA, with an overall sensitivity of 99.3% and
      specificity of 98%. Differentiation capacity was much better for the Geenius
      assay, with 93.8% of samples identified correctly as HIV-1 or HIV-2. When the new
      interpretation criteria for the LIA were used, the differentiation capacity of
      LIA increased to 98.5%. The results show that the Geenius assay is a reliable and
      fast alternative for the confirmation and differentiation of HIV-1 and HIV-2
      infection in resource-rich and poor settings. 

PMID- 25075935
TI  - A new approach to determining whole viral genomic sequences including termini
      using a single deep sequencing run.
AB  - Next-generation sequencing is now commonly used for a variety of applications in
      virology including virus discovery, investigation of quasispecies, viral
      evolution, metagenomics, and analyses of antiviral resistance. However, there are
      limitations with the current sample preparation methods used for deep sequencing
      of viral genomes, especially during de novo sequencing. For example, current
      methods are unable to capture the terminal sequences of viral genomes in an
      efficient and effective manner; data representing the 3' and 5' ends are
      typically insufficient. Methods such as Rapid Amplification of cDNA Ends address
      this issue but these methods can be time consuming, may require some prior
      knowledge of the viral sequence, and require multiple independent procedures. The
      current study outlines a sample preparation technique that overcomes some of
      these shortcomings. The method relied on random fragmentation with divalent
      cations and subsequent adapter ligation directly to RNA, rather than cDNA, to
      maximize the quality and quantity of terminal reads. The technique was tested on
      RNA samples from two different RNA viruses, Ebola virus and hepatitis C virus.
      This method permits rapid preparation of samples for deep sequencing while
      eliminating the use of sequence specific primers and captures the entire genome
      sequence, including the 5' and 3' ends. This could improve the efficiency of
      virus discovery projects where the terminal ends are unknown. 

PMID- 25075936
TI  - Enhanced accumulation of LDLs within the venous graft wall induced by elevated
      filtration rate may account for its accelerated atherogenesis.
AB  - OBJECTIVE: To test the hypothesis that the venous graft when implanted in an
      arterial bypass might endure a significantly elevated water filtration rate,
      leading to fast infiltration/accumulation of low-density lipoproteins (LDLs)
      within the graft wall and hence the accelerated atherogenesis. METHODS: We
      measured filtration rates of the swine femoral artery and lateral saphenous vein
      under venous and arterial hemodynamic conditions in vitro. Based on the measured
      filtration rates, we numerically simulated LDL transport in an arterial bypass
      model with a venous graft. Moreover, in order to validate the theoretical
      prediction, we measured DiI-LDLs uptake by both arteries and veins under arterial
      condition. RESULTS: The experimental results showed that when subjected to
      arterial hemodynamic condition, the filtration rate of the venous wall was
      increased sharply, and significantly higher than that of the artery. Moreover,
      different from the hydraulic conductivity of artery, the venous one would
      increase with increasing pressure. The numerical results showed that for the
      venous graft, both luminal surface LDL concentration and LDL accumulation within
      the vessel wall were significantly higher than those for the host artery. In
      addition, the experiment, which was used to confirm theoretical prediction,
      showed that the amount of DiI-LDLs uptake by the venous wall was much higher
      compared with arterial wall. CONCLUSION: The present study suggests that the
      accelerated atherogenesis of the venous graft is attributable to its elevated
      filtration rate that may lead to both aggravated concentration polarization of
      LDLs and enhanced convective transport of LDLs into the graft wall.

PMID- 25075937
TI  - Coronary microvascular spasm triggers transient ischemic left ventricular
      diastolic abnormalities in patients with chest pain and angiographically normal
      coronary arteries.
AB  - AIMS: Impaired coronary microvascular dilatory function can lead to exercise
      induced myocardial ischemia and angina pectoris even in patients without
      significant (>50%) obstructive coronary atherosclerosis (APWOCA). Diffuse distal
      vessel epicardial spasm and microvascular spasm have been also proposed as a
      plausible explanation for angina at rest in these patients. However, objective
      systematic evidence for the latter i.e. echocardiographic wall motion
      abnormalities during angina, is lacking at present. Coronary epicardial and
      microvascular spasm can be triggered in susceptible patients by the
      administration of intracoronary acetylcholine (Ach). We sought to assess whether
      Ach induced diffuse distal epicardial coronary artery spasm (>=75% diameter
      reduction) and coronary microvascular spasm can cause transient ischemic left
      ventricular dysfunction, as assessed by echocardiography. METHODS: 50 patients
      (19 men aged 60.5 +/- 8.9 years) with stable APWOCA were assessed for coronary
      spasm and myocardial ischemia with intracoronary Ach infusion, 2D transthoracic
      echocardiography (before and during Ach testing), continuous 12-lead ECG
      monitoring, and ultrasensitive cardiac troponin (US-cTn) measurement before and
      within 4 h after Ach testing. RESULTS: 14 patients (28%) had a "negative" Ach
      test, 14 (28%) developed coronary microvascular spasm and 17 (34%) had diffuse
      distal epicardial spasm. In 5 patients (10%) the test was inconclusive.
      Echocardiographic variables including deceleration time, EF slope and E/A, as
      well as ultrasensitive-cTn concentrations were abnormal during Ach induced
      ischemic ECG changes. CONCLUSIONS: We have, for the first time, demonstrated that
      Ach induced coronary microvascular spasm is associated with echocardiographic
      changes and ultrasensitive-cTn elevations, indicative of myocardial ischemia.

PMID- 25075938
TI  - Transcriptome analysis of newly classified bZIP transcription factors of Brassica
      rapa in cold stress response.
AB  - Plant bZIP transcription factors play crucial roles in biological processes. In
      this study, 136 putative bZIP transcription members were identified in Brassica
      rapa. The bZIP family can be divided into nine groups according to the specific
      amino acid rich domain in B. rapa and Arabidopsis thaliana. To screen the cold
      stress responsive BrbZIP genes, we evaluated whether the transcription patterns
      of the BrbZIP genes were enhanced by cold treatment in the inbred lines, Chiifu
      and Kenshin, by microarray data analysis and qRT-PCR. The expression level of six
      genes increased significantly in Kenshin, but these genes were unchanged in
      Chiifu. These findings suggest that the six genes that encoded proteins
      containing N-rich regions might be involved in cold stress response. The results
      presented herein provide valuable information regarding the molecular basis of
      the bZIP transcription factors and their potential function in regulation growth
      and development, particularly in cold stress response. 

PMID- 25075939
TI  - Electronic structure and band alignment at an epitaxial spinel/perovskite
      heterojunction.
AB  - The electronic properties of solid-solid interfaces play critical roles in a
      variety of technological applications. Recent advances of film epitaxy and
      characterization techniques have demonstrated a wealth of exotic phenomena at
      interfaces of oxide materials, which are critically dependent on the alignment of
      their energy bands across the interface. Here we report a combined photoemission
      and electrical investigation of the electronic structures across a prototypical
      spinel/perovskite heterojunction. Energy-level band alignment at an epitaxial
      Co3O4/SrTiO3(001) heterointerface indicates a chemically abrupt, type I
      heterojunction without detectable band bending at both the film and substrate.
      The unexpected band alignment for this typical p-type semiconductor on SrTiO3 is
      attributed to its intrinsic d-d interband excitation, which significantly narrows
      the fundamental band gap between the top of the valence band and the bottom of
      the conduction band. The formation of the type I heterojunction with a flat-band
      state results in a simultaneous confinement of both electrons and holes inside
      the Co3O4 layer, thus rendering the epitaxial Co3O4/SrTiO3(001) heterostructure
      to be a very promising material for high-efficiency luminescence and
      optoelectronic device applications. 

PMID- 25075940
TI  - PTPN3 mutations and HBV may exert synergistic effects in the origin of the
      intrahepatic cholangiocarcinoma.

PMID- 25075941
TI  - The Use of tenofovir disoproxil fumarate in hepatitis B e antigen-positive
      patients with normal levels of alanine aminotransferase.

PMID- 25075942
TI  - The use of AFP-based algorithm to predict hepatocellular carcinoma.

PMID- 25075943
TI  - Exome sequencing in familial colorectal cancer: searching for needles in
      haystacks.

PMID- 25075944
TI  - Reply: To PMID 25075945.

PMID- 25075945
TI  - Modifying the definition of screening exposure to settle existing differences.

PMID- 25075946
TI  - Pharmacology in ENT.

PMID- 25075947
TI  - The incidence of tympanogenic labyrinthitis ossificans.
AB  - OBJECTIVE: To estimate the incidence of tympanogenic labyrinthitis ossificans.
      METHODS: The records of patients treated with mastoidectomy for various
      tympanogenic aetiologies from January 2007 to December 2011 were retrospectively
      reviewed. Patients whose high-resolution computed tomography scans showed
      evidence of labyrinthine calcification of the temporal bone were enrolled.
      Patients with a history of head and neck cancer, meningitis, and otosclerosis,
      and patients with cochlear implants, were excluded from this study. RESULTS: A
      total of 195 patients were enrolled in this study; 4 of the patients presented
      with calcification in the inner ear. Therefore, the incidence of tympanogenic
      labyrinthitis ossification was 2 per cent. The computed tomography findings
      revealed: (1) cochlear calcifications of the basal and middle turn in two
      patients; and (2) vestibular, superior semicircular canal, posterior semicircular
      canal and lateral semicircular canal calcification in one, four, three and two
      patients, respectively. CONCLUSION: The incidence of tympanogenic labyrinthitis
      ossification in patients who had undergone a mastoidectomy was 2 per cent.

PMID- 25075948
TI  - Clinical and biological acceptance of a fibrocollagen-coated mersylene patch for
      tracheal repair in growing dogs.
AB  - BACKGROUND: Collagen-covered prostheses can be used as a non-circumferential
      segmental tracheal replacement. However, the applicability of these implants in
      young subjects has not yet been reported. METHODS: In this experimental,
      longitudinal study, dogs aged 29-32 days underwent limited segmental tracheal
      replacement with a polyester prosthesis or were allocated to a control, untreated
      group. The dogs were evaluated clinically, endoscopically and tomographically for
      up to one year. RESULTS: Although there was evidence of tracheal growth in the
      experimental group, tomographic measurements were significantly smaller in this
      group than in the control group throughout the observation period. At the end of
      the study, there was no evidence of implant rejection, stenosis or collapse.
      Normal respiratory epithelium had grown across the implanted membrane in the
      experimental group. CONCLUSION: The homologous collagen mersylene membrane
      allowed for limited structural tracheal growth and was functionally integrated
      into the segmented tracheal wall in growing dogs.

PMID- 25075949
TI  - Sinonasal malignancy: presentation and outcomes.
AB  - OBJECTIVE: We wanted to identify the presentation, diagnostic work-up and
      treatment outcomes of patients with sinonasal malignancy at Derriford Hospital,
      Plymouth, UK and compare these with the European Position Paper on Endoscopic
      Management of Tumours of the Nose, Paranasal Sinuses and Skull Base. MATERIALS
      AND METHODS: This was a retrospective audit of all patients diagnosed with
      sinonasal malignancy over a five-year period. The clinical records and picture
      archiving and communications system data of the patients were reviewed. RESULTS:
      Thirty patients with sinonasal malignancy were identified out of 570 head and
      neck cancer patients. The nasal cavity was the most common site for presentation,
      followed by the maxillary sinuses. Fifty per cent of patients had a squamous cell
      carcinoma and 27 per cent had a malignant melanoma. Half of the patients
      presented at stage IV of the cancer and 20 per cent at stage III. Thirty-seven
      per cent of patients underwent surgical management and only 20 per cent of the
      total patient group underwent endoscopic surgery. The mortality in our series was
      30 per cent over the studied period. CONCLUSION: Late-stage presentation of
      sinonasal malignancy has resulted in increased patient mortality in our case
      series. Also, we found a high incidence of malignant melanoma with high
      recurrence and survival rates.

PMID- 25075950
TI  - Influence of rumen protozoa on methane emission in ruminants: a meta-analysis
      approach.
AB  - A meta-analysis was conducted to evaluate the effects of protozoa concentration
      on methane emission from ruminants. A database was built from 59 publications
      reporting data from 76 in vivo experiments. The experiments included in the
      database recorded methane production and rumen protozoa concentration measured on
      the same groups of animals. Quantitative data such as diet chemical composition,
      rumen fermentation and microbial parameters, and qualitative information such as
      methane mitigation strategies were also collected. In the database, 31% of the
      experiments reported a concomitant reduction of both protozoa concentration and
      methane emission (g/kg dry matter intake). Nearly all of these experiments tested
      lipids as methane mitigation strategies. By contrast, 21% of the experiments
      reported a variation in methane emission without changes in protozoa numbers,
      indicating that methanogenesis is also regulated by other mechanisms not
      involving protozoa. Experiments that used chemical compounds as an
      antimethanogenic treatment belonged to this group. The relationship between
      methane emission and protozoa concentration was studied with a variance
      covariance model, with experiment as a fixed effect. The experiments included in
      the analysis had a within-experiment variation of protozoa concentration higher
      than 5.3 log10 cells/ml corresponding to the average s.e.m. of the database for
      this variable. To detect potential interfering factors for the relationship, the
      influence of several qualitative and quantitative secondary factors was tested.
      This meta-analysis showed a significant linear relationship between methane
      emission and protozoa concentration: methane (g/kg dry matter intake)=
      30.7+8.14*protozoa (log10 cells/ml) with 28 experiments (91 treatments), residual
      mean square error=1.94 and adjusted R 2=0.90. The proportion of butyrate in the
      rumen positively influenced the least square means of this relationship. 

PMID- 25075951
TI  - Anti-laminin gamma1 pemphigoid associated with pustular psoriasis.

PMID- 25075952
TI  - Progressive aneurysmal dilation of coronary arterial fistula after transcatheter
      closure: successfully treated by a second occlusion device.
AB  - We report on a 6-year-old boy with a huge right coronary artery to the right
      ventricle fistula, who had previously been treated by device closure at the right
      ventricular exit point. However, 3 years later, the right coronary artery
      aneurysm showed progressively dilation and compressed the right ventricle. To
      prevent further complications related to the aneurysm, the proximal part of the
      aneurysm was successfully occluded by a vascular plug. 

PMID- 25075953
TI  - Paraffin treasures: do they last forever?
AB  - Formalin-fixed paraffin-embedded (FFPE) tissues stored in Departments of
      Pathology have become valuable sources of material for both diagnostic and
      research purposes. Obtaining nucleic acids from this material may be challenging,
      especially after storage for several years. The present study was aimed at
      evaluating DNA degradation over time by comparing the quality of DNA obtained in
      2002 with the quality of DNA obtained in 2010 from the same paraffin blocks. The
      DNA obtained after several years from FFPE tissues was, in the majority of cases,
      of lower quality in terms of amplifiable length of nuclear DNA by PCR, and only a
      minority of them are still equally amplifiable. For this reason, if it is
      suspected that a molecular analysis may be necessary in the future, it would be
      important to obtain nucleic acids shortly after the diagnostic process is over
      or, when possible, to keep frozen samples at the institutional biorepository. 

PMID- 25075954
TI  - High-risk case identification for use in comprehensive complex care management.
AB  - The current study aimed to develop a patient selection process for muiltimorbid
      care management that balances the needs to accurately identify patients who are
      at risk for future high costs and assures that those selected can clinically
      benefit from proactive care management. Six physicians were surveyed on
      characteristics of their current (2012) patients to elicit clinical
      considerations for high-risk patient identification. Data from 2010-2011 were
      extracted from Clalit Health Services' (Israel's largest managed care
      organization) comprehensive database to derive the Adjusted Clinical Groups (ACG)
      predictive model risk scores for risk of future high costs. Model discriminatory
      power was assessed using the c-statistic and positive predictive value (PPV),
      before and after application of the clinical exclusion criteria. Inclusion
      criteria were refined based on physician input from a survey on 375 patients.
      Recommended reasons for exclusion: active cancer, schizophrenia, dialysis,
      residence in nursing homes or long-term care facilities, and age 95 years or
      older. The high-risk group included 5341 patients (mean 50 patients per
      physician). The c-statistic of the ACG model before and after exclusions applied
      was 0.80 and 0.75, respectively. After exclusion, the PPV for the 6% highest risk
      patients was 40%. High-risk patients' age, number of chronic conditions, and
      utilization were substantially higher than those of all other patients. This
      study shows that a validated predictive modeling tool provides acceptable
      discriminatory power for selecting multimorbid patients for participation in
      proactive care management, even after some of the highest risk patients are
      excluded because of priori clinical considerations.

PMID- 25075955
TI  - Saudi practical guidelines on biologic treatment of psoriasis.
AB  - The current treatment of psoriasis patients with biologic agents in the Kingdom
      of Saudi Arabia (KSA) is mainly based on clinical experience. Although there are
      published international guidelines for treatment with biologics, such as the
      European S3 guidelines (a joint project of the European Dermatology Forum, the
      European Academy of Dermatology and Venereology, and the International Psoriasis
      Council), many nations have found it beneficial to develop country-based
      guidelines that incorporate specific regional aspects of therapy (legal and
      practical). With the expanded role of biologic agents in the treatment of
      psoriasis in Saudi Arabia, a need for local Saudi guidelines has become evident.
      Here we present a practical approach to the evidence-based clinical
      administration of biologics for professionals who treat patients with psoriasis. 

PMID- 25075956
TI  - Film thickness of dentin desensitizing agents on full crown preparations:
      influence of product and gravity.
AB  - OBJECTIVE: To determine the thickness of resin layer formed when dentin
      desensitizing agents are applied to teeth prepared for full crown restorations.
      DESIGN: In vitro measurements of resin layer thickness. METHODS AND MATERIALS:
      Forty caries-free human premolar teeth were prepared as for a full metal-ceramic
      crown restoration with a retention groove placed mesiobuccally. Stratified
      allocation created five groups of eight teeth, which were treated with various
      desensitizing agents. Four teeth within each group were treated upright, and four
      were treated while inverted, resulting in a total of 10 experimental groups.
      Teeth were sectioned and resin layer thickness measured under an environmental
      scanning electron microscope at certain sites across the section. RESULTS:
      Analysis was carried out using three-way analysis of variance. On flat tooth
      surfaces, light-cured resins (Prime & Bond and Seal & Protect) formed layers of
      16.2 +/- 8.9 MUm and 23.4 +/- 10.6 MUm, respectively. More concave sites had
      significantly thicker layers (p<0.05) than flat or convex sites. At the internal
      shoulder angle, mean thicknesses were 84.1 +/- 27.8 MUm and 104.3 +/- 56.6 MUm,
      respectively. At the retention groove, figures were 86.6 +/- 3.13 MUm and 136.2
      +/- 72.0 MUm. Differences between these two resins were not significant (p>0.05).
      Light-cured resins formed significantly thicker layers on inverted samples at the
      occlusal indentation only (p=0.004), with a mean of 66.9 +/- 21.6 MUm; upright
      samples had a mean of 36.6 +/- 12.4 MUm. Self-activating resins (Pain-Free
      Desensitizer, Viva Sens, and Gluma Desensitizer) formed no consistent layers.
      CONCLUSION: Within the limitations of this in vitro study, light-cured resins
      consistently pooled in convex areas of crown preparations. A great portion of
      retention grooves can potentially become occluded by resin. The self-activating
      products tested did not form significant layers.

PMID- 25075957
TI  - Saponins: the phytochemical with an emerging potential for curing clinical
      depression.
AB  - Depression is on the rise globally and expected to lead in global burden of
      diseases by 2030. The current therapy has serious limitations in terms of safety,
      efficacy, tolerability and therapeutic success. This review, based on the
      literature of the last decade, is aimed at exploring the preclinical profile of
      plant-based saponins (the abundant secondary metabolite) as an emerging therapy
      for depression. Enough scientific evidences reflect that saponins promote
      neurogenesis, restore monoaminergic tone and enhance neurotrophic factors. In
      multiple stress models, they have exhibited adaptogenic effects via normalising
      hypothalamus-pituitary-adrenal axis, corticosterone levels and oxidative stress.
      Scientific data revealed neuroprotective effect of saponins by inhibiting
      apoptosis and intraneuronal calcium dynamics. Many plants possessing saponins as
      their principal antidepressant moiety need investigation at clinical level. Last
      decade literature revealed numerous preclinical reports supporting the role of
      saponins as natural cure for depression and justified their inclusion in
      antidepressant drug discovery programs. 

PMID- 25075958
TI  - 4- Pubertal and Adult Testis.
AB  - Abstract The testis is a complex organ that undergoes significant changes from
      puberty to adulthood. An accurate knowledge of its histology, ultrastructure and
      physiological-morphological maturation process is required in order to interpret
      the many variations within the normal and abnormal (pathological) conditions.
      Here we describe in detail the different testicular compartments, showing
      correlations with the process of spermatogenesis at the histological and
      ultrastructural level.

PMID- 25075960
TI  - The impact of possible climate changes on developing countries: the needs for
      plants tolerant to abiotic stresses.

PMID- 25075959
TI  - Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled
      analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON).
AB  - BACKGROUND: Previous studies have evidenced an association between
      gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what
      extent these associations vary by population, age, sex, body mass index, and
      cigarette smoking, or whether duration and frequency of symptoms interact in
      predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON)
      allowed an in-depth assessment of these issues. METHODS: Detailed information on
      heartburn and regurgitation symptoms and covariates were available from five
      BEACON case-control studies of EA and esophagogastric junction adenocarcinoma
      (EGJA). We conducted single-study multivariable logistic regressions followed by
      random-effects meta-analysis. Stratified analyses, meta-regressions, and
      sensitivity analyses were also conducted. RESULTS: Five studies provided 1,128 EA
      cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates
      indicated positive, significant associations between heartburn/regurgitation
      symptoms and EA. Increasing heartburn duration was associated with increasing EA
      risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years,
      10 to <20 years, and >=20 years. Associations with EGJA were slighter weaker, but
      still statistically significant for those with the highest exposure. Both
      frequency and duration of heartburn/regurgitation symptoms were independently
      associated with higher risk. We observed similar strengths of associations when
      stratified by age, sex, cigarette smoking, and body mass index. CONCLUSIONS: This
      analysis indicates that the association between heartburn/regurgitation symptoms
      and EA is strong, increases with increased duration and/or frequency, and is
      consistent across major risk factors. Weaker associations for EGJA suggest that
      this cancer site has a dissimilar pathogenesis or represents a mixed population
      of patients.

PMID- 25075962
TI  - Radium 223 dichloride: a multidisciplinary approach to metastatic castration
      resistant prostate cancer.
AB  - The role of nuclear medicine physicians in the multidisciplinary team for the
      management of patients with prostate cancer has been restricted because of a lack
      of available tools. The only drugs approved to relieve pain related to bone
      metastases were beta-emitting radiopharmaceuticals. These drugs did not prove to
      prolong survival when used as single agent and resulted associated with important
      adverse events. This situation has changed with the introduction of radium 223
      because of evidence of improved survival in patients, the good safety profile and
      the opportunity to avoid clonal selection of tumor cells. Cooperation among
      physicians involved in cancer management will lead to improvements in the
      treatment of bone metastases due to prostate cancer and is thought to extend to
      other tumor types.

PMID- 25075963
TI  - Molecular phylogenetic analysis reveals the new genus Hemisphaericaspora of the
      family Debaryomycetaceae.
AB  - Four strains of a novel ascomycetous yeast species were recovered from the frass
      of wood-boring beetles collected from the Baotianman Nature Reserve and the
      Laojieling Nature Reserve in Henan Province, China. This species produced
      unconjugated and deliquescent asci with hemispheroid or helmet-shaped ascospores.
      Analysis of gene sequences for the D1/D2 domain of the large subunit (LSU) rRNA,
      as well as analysis of concatenated gene sequences for the nearly complete small
      subunit (SSU) rRNA and D1/D2 domain of the large subunit (LSU) rRNA placed the
      novel species in a small clade including only one recognised species, Candida
      insectamans, in the family Debaryomycetaceae (Saccharomycotina, Ascomycota). DNA
      sequence analyses demonstrated that the novel species was distinct from all
      currently recognised teleomorphic yeast genus. The name Hemisphaericaspora
      nanyangensis gen nov., sp. nov. is proposed to accommodate the novel genus and
      species. The new genus can be distinguished from closely related teleomorphic
      genera Lodderomyces and Spathaspora through sequence comparison and ascospore
      morphology. The ex-type strain of H. nanyangensis is CBS 13020T ( = CICC 33021 =
      NYNU 13717). Furthermore, based on phenotypic and genotypic characteristics, C.
      insectamans is transferred to the newly described genus as Hemisphaericaspora
      insectamans comb. nov., in accordance with the changes in the International Code
      of Nomenclature for algae, fungi and plants. 

PMID- 25075961
TI  - Non-invasive pneumococcal pneumonia in Portugal--serotype distribution and
      antimicrobial resistance.
AB  - There is limited information on the serotypes causing non-invasive pneumococcal
      pneumonia (NIPP). Our aim was to characterize pneumococci causing NIPP in adults
      to determine recent changes in serotype prevalence, the potential coverage of
      pneumococcal vaccines and changes in antimicrobial resistance. Serotypes and
      antimicrobial susceptibility profiles of a sample of 1300 isolates recovered from
      adult patients (>=18 yrs) between 1999 and 2011 (13 years) were determined.
      Serotype 3 was the most frequent cause of NIPP accounting for 18% of the
      isolates. The other most common serotypes were 11A (7%), 19F (7%), 19A (5%), 14
      (4%), 22F (4%), 23F (4%) and 9N (4%). Between 1999 and 2011, there were
      significant changes in the proportion of isolates expressing vaccine serotypes,
      with a steady decline of the serotypes included in the 7-valent conjugate vaccine
      from 31% (1999-2003) to 11% (2011) (P<0.001). Taking together the most recent
      study years (2009-2011), the potential coverage of the 13-valent conjugate
      vaccine was 44% and of the 23-valent polysaccharide vaccine was 66%. While
      erythromycin resistance increased from 8% in 1999-2003 to 18% in 2011 (P<0.001),
      no significant trend was identified for penicillin non-susceptibility, which had
      an average value of 18.5%. The serotype distribution found in this study for NIPP
      was very different from the one previously described for IPD, with only two
      serotypes in common to the ones responsible for half of each presentation in 2009
      2011 - serotypes 3 and 19A. In spite of these differences, the overall prevalence
      of resistant isolates was similar in NIPP and in IPD.

PMID- 25075964
TI  - Raised trappin2/elafin protein in cervico-vaginal fluid is a potential predictor
      of cervical shortening and spontaneous preterm birth.
AB  - Early spontaneous preterm birth is associated with inflammation/infection and
      shortening of the cervix. We hypothesised that cervico-vaginal production of
      trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide
      (cathelicidin), key components of the innate immune system, are altered in women
      who have a spontaneous preterm birth. The aim was to determine the relationship
      between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein
      concentrations with cervical length in woman at risk of spontaneous preterm
      birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal
      CVF samples (taken between 13 to 30 weeks' gestation) from 74 asymptomatic high
      risk women (based on obstetric history) recruited prospectively. Thirty six women
      developed a short cervix (<25 mm) by 24 weeks' and 38 women did not. Women who
      developed a short cervix had 2.71 times higher concentrations of CVF
      trappin2/elafin from 14 weeks' versus those who did not (CI 1.94-3.79, p<0.0005).
      CVF trappin2/elafin before 24 weeks' was 1.79 times higher in women who had a
      spontaneous preterm birth <37 weeks' (CI: 1.05-3.05, p = 0.034). Trappin2/elafin
      (>200 ng/ml) measured between 14+0-14+6 weeks' of pregnancy predicted women who
      subsequently developed a short cervix (n = 11, ROC area = 1.00, p = 0.008) within
      8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D
      status did not correlate with CVF antimicrobial peptide concentrations. Raised
      CVF trappin2/elafin has potential as an early pregnancy test for prediction of
      cervical shortening and spontaneous preterm birth. This justifies validation in a
      larger cohort.

PMID- 25075966
TI  - Understanding the role of saliva in aroma release from wine by using static and
      dynamic headspace conditions.
AB  - The aim of this work was to determine the role of saliva in wine aroma release by
      using static and dynamic headspace conditions. In the latter conditions, two
      different sampling points (t = 0 and t = 10 min) corresponding with oral (25.5 
      degrees C) and postoral phases (36  degrees C) were monitored. Both methodologies
      were applied to reconstituted dearomatized white and red wines with different
      nonvolatile wine matrix compositions and a synthetic wine (without matrix
      effect). All of the wines had the same ethanol concentration and were spiked with
      a mixture of 45 aroma compounds covering a wide range of physicochemical
      characteristics at typical wine concentrations. Two types of saliva (human and
      artificial) or control samples (water) were added to the wines. The adequacy of
      the two headspace methodologies for the purposes of the study (repeatability,
      linear ranges, determination coefficients, etc.) was previously determined. After
      application of different chemometric analysis (ANOVA, LSD, PCA), results showed a
      significant effect of saliva on aroma release dependent on saliva type
      (differences between artificial and human) and on wine matrix using static
      headspace conditions. Red wines were more affected than white and synthetic wines
      by saliva, specifically human saliva, which provoked a reduction in aroma release
      for most of the assayed aroma compounds independent of their chemical structure.
      The application of dynamic headspace conditions using a saliva bioreactor at the
      two different sampling points (t = 0 and t = 10 min) showed a lesser but
      significant effect of saliva than matrix composition and a high influence of
      temperature (oral and postoral phases) on aroma release. 

PMID- 25075968
TI  - Flame-driven aerosol synthesis of copper-nickel nanopowders and conductive
      nanoparticle films.
AB  - We report the continuous one-step synthesis of bimetallic copper-nickel
      nanostructured coatings by deposition and sintering of metal nanoparticles
      produced as an aerosol using a flame driven high temperature reducing jet (HTRJ)
      process. The HTRJ process allows gas-phase (aerosol) formation of metal
      nanoparticles from low-cost metal salt precursors. These can be collected as
      discrete powders for subsequent use in formulating conductive inks or for other
      applications. However, direct deposition of nanoparticles to form coatings allows
      measurements of electrical conductivity of films of deposited nanoparticles as a
      function of composition and sintering temperature, without actually formulating
      and printing inks. This is the approach taken here for the purpose of screening
      nanoparticle compositions quickly. We characterized the microstructure and
      composition of both nanopowders and films and found that their composition
      consistently matched the ratio of metals in the precursor solution. The
      electrical conductivity was highest (~10(4) S/m) for films with 60:40 and 40:60
      copper-to-nickel mass ratios. These films maintained their conductivity during
      extended storage (1 month) under ambient conditions. The oxidation resistance and
      high conductivity observed here suggest that 60:40 and 40:60 Cu:Ni nanoparticles
      have promise as lower cost replacements for silver nanoparticles in conductive
      ink formulations. 

PMID- 25075967
TI  - Transcriptome of the female synganglion of the black-legged tick Ixodes
      scapularis (Acari: Ixodidae) with comparison between Illumina and 454 systems.
AB  - Illumina and 454 pyrosequencing were used to characterize genes from the
      synganglion of female Ixodes scapularis. GO term searching success for biological
      processes was similar for samples sequenced by both methods. However, for
      molecular processes, it was more successful for the Illumina samples than for 454
      samples. Functional assignments of transcripts predicting neuropeptides,
      neuropeptide receptors, neurotransmitter receptors and other genes of interest
      was done, supported by strong e-values (<-6), and high consensus sequence
      alignments. Transcripts predicting 15 putative neuropeptide prepropeptides
      ((allatostatin, allatotropin, bursicon alpha, corticotropin releasing factor
      (CRF), CRF-binding protein, eclosion hormone, FMRFamide, glycoprotein A, insulin
      like peptide, ion transport peptide, myoinhibitory peptide, inotocin ( = 
      neurophysin-oxytocin), Neuropeptide F, sulfakinin and SIFamide)) and transcripts
      predicting receptors for 14 neuropeptides (allatostatin, calcitonin,
      cardioacceleratory peptide, corazonin, CRF, eclosion hormone, gonadotropin
      releasing hormone/AKH-like, insulin-like peptide, neuropeptide F, proctolin,
      pyrokinin, SIFamide, sulfakinin and tachykinin) are reported. Similar to
      Dermacentor variabilis, we found transcripts matching pro-protein convertase,
      essential for converting neuropeptide hormones to their mature form.
      Additionally, transcripts predicting 6 neurotransmitter/neuromodulator receptors
      (acetylcholine, GABA, dopamine, glutamate, octopamine and serotonin) and 3
      neurotransmitter transporters (GABA transporter, noradrenalin-norepinephrine
      transporter and Na+-neurotransmitter/symporter) are described. Further, we found
      transcripts predicting genes for pheromone odorant receptor, gustatory receptor,
      novel GPCR messages, ecdysone nuclear receptor, JH esterase binding protein,
      steroidogenic activating protein, chitin synthase, chitinase, and other genes of
      interest. Also found were transcripts predicting genes for spermatogenesis
      associated protein, major sperm protein, spermidine oxidase and spermidine
      synthase, genes not normally expressed in the female CNS of other invertebrates.
      The diversity of messages predicting important genes identified in this study
      offers a valuable resource useful for understanding how the tick synganglion
      regulates important physiological functions. 

PMID- 25075969
TI  - Nickel hydroxide/cobalt-ferrite magnetic nanocatalyst for alcohol oxidation.
AB  - A magnetically separable, active nickel hydroxide (Bronsted base) coated
      nanocobalt ferrite catalyst has been developed for oxidation of alcohols. High
      surface area was achieved by tuning the particle size with surfactant. The
      surface area of 120.94 m2 g(-1) has been achieved for the coated nanocobalt
      ferrite. Improved catalytic activity and selectivity were obtained by synergistic
      effect of transition metal hydroxide (basic hydroxide) on nanocobalt ferrite. The
      nanocatalyst oxidizes primary and secondary alcohols efficiently (87%) to
      corresponding carbonyls in good yields.

PMID- 25075971
TI  - Locked ortho- and para-core chromophores of green fluorescent protein; dramatic
      emission enhancement via structural constraint.
AB  - We report the design strategy and synthesis of a structurally locked GFP core
      chromophore p-LHBDI, its ortho-derivative, o-LHBDI, and H2BDI possessing both
      para- and ortho-hydroxyl groups such that the inherent rotational motion of the
      titled compounds has been partially restricted. o-LHBDI possesses a doubly locked
      configuration, i.e., the seven-membered ring hydrogen bond and five-membered ring
      C(4-5-10-13-14) cyclization, from which the excited-state intramolecular proton
      transfer takes place, rendering a record high tautomer emission yield (0.18 in
      toluene) and the generation of amplified spontaneous emission. Compared with
      their unlocked counterparts, a substantial increase in the emission yield is also
      observed for p-LHBDI and H2BDI in anionic forms in water, and accordingly the
      structure versus luminescence relationship is fully discussed based on their
      chemistry and spectroscopy aspect. In solid, o-LHBDI exhibits an H-aggregate-like
      molecular packing, offers narrow-bandwidth emission, and has been successfully
      applied to fabricate a yellow organic light emitting diodes (lambdamax = 568 nm,
      etaext = 1.9%) with an emission full width at half-maximum as narrow as 70 nm. 

PMID- 25075970
TI  - The associations between immunity-related genes and breast cancer prognosis in
      Korean women.
AB  - We investigated the role of common genetic variation in immune-related genes on
      breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer
      patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A
      total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related
      genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A
      multivariate Cox-proportional hazard model and polygenic risk score model were
      used to estimate the effects of SNPs on breast cancer prognosis. Harrell's C
      index was calculated to estimate the predictive accuracy of polygenic risk score
      model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP) was
      conducted to approximate the biological pathway. In addition, to confirm our
      results with current evidence, previous studies were systematically reviewed.
      Sixty-two SNPs were statistically significant at p-value less than 0.05. The most
      significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR) = 11.99, 95% CI
      = 3.62-39.72, P = 4.84E-05), rs2289278 in TSLP gene (HR = 4.25, 95% CI = 2.10
      8.62, P = 5.99E-05) and rs2074724 in HGF gene (HR = 4.63, 95% CI = 2.18-9.87, P =
      7.04E-05). In the polygenic risk score model, the HR of women in the 3rd tertile
      was 6.78 (95% CI = 1.48-31.06) compared to patients in the 1st tertile of
      polygenic risk score. Harrell's C index was 0.813 with total patients and 0.924
      in 4-fold cross validation. In the pathway analysis, 18 pathways were
      significantly associated with breast cancer prognosis (P<0.1). The IL-6R, IL-8,
      IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data
      of both our study and a previous study. Therefore, our results suggest that
      genetic polymorphisms in immune-related genes have relevance to breast cancer
      prognosis among Korean women. 

PMID- 25075974
TI  - Expeditious metal-free access to functionalized polycyclic acetals under mild
      aqueous conditions.
AB  - A facile approach for the synthesis of furopyrans and bicyclic bisacetals under
      mild aqueous conditions is described. This potentially green, diversity oriented
      approach involves cascade Michael addition and cycloacetalization of pyranones
      and 1,3-dicarbonyls. An interesting switch in the product class was observed
      depending on the type of pyranone employed. Products of type I and II obtained
      herein are an integral part of several bioactive natural products and medicinally
      interesting compounds. 

PMID- 25075973
TI  - Maladjusted host immune responses induce experimental cerebral malaria-like
      pathology in a murine Borrelia and Plasmodium co-infection model.
AB  - In the Plasmodium infected host, a balance between pro- and anti-inflammatory
      responses is required to clear the parasites without inducing major host
      pathology. Clinical reports suggest that bacterial infection in conjunction with
      malaria aggravates disease and raises both mortality and morbidity in these
      patients. In this study, we investigated the immune responses in BALB/c mice, co
      infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium
      Borrelia duttonii. In contrast to single infections, we identified in the co
      infected mice a reduction of L-Arginine levels in the serum. It indicated
      diminished bioavailability of NO, which argued for a dysfunctional endothelium.
      Consistent with this, we observed increased sequestration of CD8+ cells in the
      brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co
      infected mice further showed an increased inflammatory response through IL-1beta
      and TNF-alpha, as well as inability to down regulate the same through IL-10. In
      addition we found loss of synchronicity of pro- and anti-inflammatory signals
      seen in dendritic cells and macrophages, as well as increased numbers of
      regulatory T-cells. Our study shows that a situation mimicking experimental
      cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and
      control over regulatory mechanisms in antigen presenting cells. 

PMID- 25075976
TI  - Fluorescence quenching studies of gamma-butyrolactone binding protein (CprB) from
      Streptomyces coelicolor A3(2).
AB  - Quorum sensing is a cell density dependent phenomenon that utilizes small
      molecule inducers like gamma-butyrolactones (GBLs) and their receptor proteins
      for adaptation to the environment. The cognate GBLs that bind to several of this
      GBL receptor family of proteins remain elusive. Here, using CprB protein from
      Streptomyces coelicolor A3(2) as a model system, we devise a method suited for
      ligand screening that would be applicable to the entire family of GBL receptors.
      Docking studies were performed to confirm the identity of the ligand binding
      pocket, and it was ascertained that the common gamma-butyrolactone moiety
      interacts with the conserved tryptophan residue (W127) residing in the ligand
      binding pocket. The presence of W127 in the cavity was exploited to monitor its
      fluorescence quenching on the addition of two chemically synthesized GBLs.
      Analysis of the data with both the native and W185L mutant versions of the
      protein confirmed that the compounds used as quenchers reside in the ligand
      binding pocket. Furthermore, fluorescence lifetime and potassium iodide (KI)
      quenching studies established that the quenching is static in nature and that the
      tryptophan residue is buried and inaccessible to surface quenchers. Additionally,
      a combination of concentration dependent fluorescence quenching and dynamic light
      scattering experiments revealed that the binding properties of the protein are
      concentration dependent and it was concluded that the most efficient binding of
      the ligand is evoked by working at the lowest concentration of protein, providing
      a sufficient signal, where the aggregation effects are negligible. 

PMID- 25075975
TI  - Cryptosporidiosis in broiler chickens in Zhejiang Province, China: molecular
      characterization of oocysts detected in fecal samples.
AB  - Cryptosporidium is one of the most important parasites in poultry, and this
      pathogen can infect more than 30 avian species. The present study investigated
      the infection rate of Cryptosporidium among broiler chicken flocks. A total of
      385 fecal samples from broiler chickens in 7 regions of Zhejiang Province
      collected from November 2010 to January 2012 were examined by microscopy. Thirty
      eight (10%) samples were positive for Cryptosporidium infection, and 3 genotypes
      (Cryptosporidium baileyi, Cryptosporidium meleagridis, and avian genotype II)
      were identified by PCR and sequencing. A phylogenetic tree of the isolates was
      analyzed. These results suggest that cryptosporidiosis is widespread in poultry
      in Zhejiang Province, and is a potential threat to public health as well as the
      economy. This is the first report about the infection rate and molecular
      characterization of Cryptosporidium in broiler chickens in Zhejiang. 

PMID- 25075977
TI  - Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the
      Soft Coral Sarcophyton ehrenbergi.
AB  - Ten new prostaglandin derivatives (PGs), sarcoehrendins A-J (1-10), together with
      five known analogues (11-15) were isolated from the soft coral Sarcophyton
      ehrenbergi. Compounds 4-8 represented the first examples of PGs featuring an 18
      ketone group. The structures including the absolute configurations were
      elucidated on the basis of spectroscopic analysis and chemical evidence. All of
      the isolates and six synthetic analogues (3a, 3b, 4a, and 11a-11c) were screened
      for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug
      target for the treatment of asthma and chronic obstructive pulmonary disease.
      Compounds 2, 10, 11a, 11b, and 13-15 exhibited inhibition with IC50 values less
      than 10 MUM, and compound 15 (IC50 = 1.4 MUM) showed comparable activity to the
      positive control rolipram (IC50 = 0.60 MUM). The active natural PGs (2, 10, and
      13-15) represent the first examples of PDE4 inhibitors without an aromatic
      moiety, and a preliminary structure-activity relationship is also proposed. 

PMID- 25075978
TI  - Carbon profile of the managed forest sector in Canada in the 20th century: sink
      or source?
AB  - Canada contains 10% of global forests and has been one of the world's largest
      harvested wood products (HWP) producers. Therefore, Canada's managed forest
      sector, the managed forest area and HWP, has the potential to significantly
      increase or reduce atmospheric greenhouse gases. Using the most comprehensive
      carbon balance analysis to date, this study shows Canada's managed forest area
      and resulting HWP were a sink of 7510 and 849 teragrams carbon (TgC),
      respectively, in the period 1901-2010, exceeding Canada's fossil fuel-based
      emissions over this period (7333 TgC). If Canadian HWP were not produced and used
      for residential construction, and instead more energy intensive materials were
      used, there would have been an additional 790 TgC fossil fuel-based emissions.
      Because the forest carbon increases in the 20th century were mainly due to
      younger growing forests that resulted from disturbances in the 19th century, and
      future increases in forest carbon stocks appear uncertain, in coming decades most
      of the mitigation contribution from Canadian forests will likely accrue from wood
      substitution that reduces fossil fuel-based emissions and stores carbon, so long
      as those forests are managed sustainably. 

PMID- 25075979
TI  - Comparison of two intraosseous devices in adult patients in the emergency
      setting: a pilot study.
AB  - OBJECTIVE: To compare two intraosseous (IO) insertion devices in terms of safety
      and ease of use in patients who need urgent vascular access in the emergency
      setting following failed attempts for intravenous lines. METHODS: This
      prospective, randomized clinical study compared two different IO access devices
      in adults (>=16 years of age or weighing>40 kg) admitted to our emergency
      department with difficult peripheral venous access and in need of urgent
      intervention. The findings were compared in terms of the rates of successful
      insertion of spring-loaded impact-driven adult BIG and the battery-driven EZ-IO
      devices on the first attempt, difficulty of use, time taken to complete the
      insertion, and complication rates. RESULTS: A total of 52 patients were enrolled
      and randomized for the study. IO access was performed in 26 patients using the
      BIG device and in 26 patients using the EZ-IO device. The rates of successful
      insertion of BIG and EZ-IO devices on the first attempt were 92.3 and 84.6%,
      respectively (P=0.668). The time taken to complete the procedure was
      significantly greater in the EZ-IO group (5.2+/-2.2 s) compared with the BIG
      group (2.8+/-1.2 s) (P<0.001). Difficulty of use was scored using the visual
      analogue scale, which yielded the mean visual analogue scale for EZ-IO and BIG
      (25.4+/-12.6 and 8.6+/-6.4 mm, respectively) (P<0.001). No mechanical problems or
      technique-related complications were encountered in any of the groups.
      CONCLUSION: Both EZ-IO and BIG are shown to be reliable and safe methods for
      insertion of intravascular access in emergency conditions.

PMID- 25075980
TI  - Synthesis and properties of poly(L-lactide)-b-poly (L-phenylalanine) hybrid
      copolymers.
AB  - Hybrid materials constituted by peptides and synthetic polymers have nowadays a
      great interest since they can combine the properties and functions of each
      constitutive block, being also possible to modify the final characteristics by
      using different topologies. Poly(l-lactide-b-l-phenylalanine) copolymers with
      various block lengths were synthesized by sequential ring-opening polymerization
      of l-lactide and the N-carboxyanhydride of l-phenylalanine. The resulting block
      copolymers were characterized by NMR spectrometry, IR spectroscopy, gel
      permeation chromatography, MALDI-TOF and UV-vis, revealing the successful
      incorporation of the polyphenylalanine (PPhe) peptide into the previously formed
      poly(l-lactide) (PLLA) polymer chain. X-ray diffraction and DSC data also
      suggested that the copolymers were phase-separated in domains containing either
      crystalline PLLA or PPhe phases. A peculiar thermal behavior was also found by
      thermogravimetric analysis when polyphenylalanine blocks were incorporated into
      polylactide. 

PMID- 25075972
TI  - Female mate choice can drive the evolution of high frequency echolocation in
      bats: a case study with Rhinolophus mehelyi.
AB  - Animals employ an array of signals (i.e. visual, acoustic, olfactory) for
      communication. Natural selection favours signals, receptors, and signalling
      behaviour that optimise the received signal relative to background noise. When
      the signal is used for more than one function, antagonisms amongst the different
      signalling functions may constrain the optimisation of the signal for any one
      function. Sexual selection through mate choice can strongly modify the effects of
      natural selection on signalling systems ultimately causing maladaptive signals to
      evolve. Echolocating bats represent a fascinating group in which to study the
      evolution of signalling systems as unlike bird songs or frog calls, echolocation
      has a dual role in foraging and communication. The function of bat echolocation
      is to generate echoes that the calling bat uses for orientation and food
      detection with call characteristics being directly related to the exploitation of
      particular ecological niches. Therefore, it is commonly assumed that echolocation
      has been shaped by ecology via natural selection. Here we demonstrate for the
      first time using a novel combined behavioural, ecological and genetic approach
      that in a bat species, Rhinolophus mehelyi: (1) echolocation peak frequency is an
      honest signal of body size; (2) females preferentially select males with high
      frequency calls during the mating season; (3) high frequency males sire more off
      spring, providing evidence that echolocation calls may play a role in female mate
      choice. Our data refute the sole role of ecology in the evolution of echolocation
      and highlight the antagonistic interplay between natural and sexual selection in
      shaping acoustic signals. 

PMID- 25075981
TI  - The first mutation identified in a Chinese acrodysostosis patient confirms a
      p.G289E variation of PRKAR1A causes acrodysostosis.
AB  - Acrodysostosis is a rare skeletal dysplasia, which has not been reported
      previously in patients of Chinese origin. The PRKAR1A gene and PDE4D gene have
      been found to be causative genes of acrodysostosis. A Chinese girl with
      acrodysostosis and concomitant multiple hormone resistance was recruited for our
      study. Clinical and biochemical characters were analyzed. DNA was extracted from
      leukocytes and was sequenced for GNAS, PDE4D and PRKAR1A gene mutations. A de
      novo heterozygous missense mutation (c.866G>A/p.G289E) was identified in the
      PRKAR1A gene. This mutation coincided with a mutation that had been found in a
      patient from another ethnic group. Our findings further suggest that the
      c.866G>A/p.G289E mutation in the PRKAR1A gene may be the cause of acrodysostosis
      with concomitant multiple hormone resistance. Moreover, it is the first report of
      acrodysostosis genetic analysis of Chinese origin. 

PMID- 25075984
TI  - Key-Vertebral Screws Strategy for Main Thoracic Curve Correction in Patients With
      Adolescent Idiopathic Scoliosis.
AB  - STUDY DESIGN: The following study was a prospective radiographic and
      retrospective clinical data assessment of adolescent idiopathic scoliosis (AIS)
      patients who had undergone a key-vertebral screws strategy (KVSS) at a single
      institution, with a minimum of 2 years' follow-up. OBJECTIVES: The aim of the
      study was to introduce the KVSS for the operative treatment of AIS of the main
      thoracic curve, and to address the role of the fulcrum-bending radiograph (FBR)
      in predicting the outcome of surgical management by this method. SUMMARY OF
      BACKGROUND DATA: The application of multilevel pedicle screws for the main
      thoracic curve in AIS patients is popular in an effort to provide spinal
      stability, enhance fusion outcome, and provide optimal curve correction. However,
      with the application of pedicle screw also comes a potential risk for soft tissue
      and neural injury and increased health care costs. It remains unknown whether
      limited screw placement can provide proper curve correction without compromising
      patient outcome. METHODS: A total of 17 consecutive patients with AIS extending
      to the main thoracic spine, who had undergone posterior fusion and fixation by
      the KVSS, a procedure in which screws are placed at important strategic points in
      the spine (ie, bilaterally at the upper and lower end segments of the fusion
      block, apical vertebra on the convex side, adjacent cephalad, and caudal screw
      placement on the concave side), at a single institution, with a minimum of 2
      year' follow-up, were included. The assessment of preoperative standing
      posteroanterior and sagittal, FBR, and postoperative standing posteroanterior and
      sagittal plain radiographs were assessed in all patients. The flexibility of the
      curve as well as the fulcrum-bending correction index (FBCI) were calculated for
      all patients. Postoperatively, radiographs were assessed at the immediate (ie, 1
      wk) and last follow-up. Clinical assessment entailed evaluation of patient
      demographics and the presence of any intraoperative or postoperative
      complications. RESULTS: The mean age at the time of surgery was 15.6 years. The
      mean follow-up was 39.8 months. The average FBR flexibility was 62.2%. The mean
      immediate curve correction was 71.2%, which did not differ in comparison with the
      last follow-up assessment (P>0.05). The mean immediate and last follow-up FBCIs
      were 119.3% and 112.5%, respectively (P=0.079). A significant negative
      correlation was found between immediate FBCI to that of the FBR curve flexibility
      (r=-0.706; P=0.002), which remained similar on the last follow-up (r=-0.681;
      P=0.003). Sagittal alignment did not significantly change from the immediate to
      last follow-up (P=0.163) Fusion was achieved in all patients. No instrumentation
      related complications were noted. CONCLUSIONS: Key-vertebral screws strategy is a
      safe and cost-effective method for the surgical treatment of the main thoracic
      curve in AIS patients. Moreover, in the context of this strategy, the FBR may
      have some predictive utility in the correction of the main thoracic curve in AIS
      patients.

PMID- 25075985
TI  - Clinical significance of postdecompression facet joint effusion after minimally
      invasive decompression for degenerative lumbar spinal stenosis.
AB  - STUDY DESIGN: A retrospective case series study. OBJECTIVE: To investigate the
      clinical significance of postdecompression facet effusion (PDFE) after
      microendoscopic decompressive laminotomy (MEDL). SUMMARY OF BACKGROUND DATA: The
      facet joint effusion noted on magnetic resonance imaging was considered as an
      indicator of degeneration of the facet joints and segmental instability. PDFE
      occurring after MEDL might imply postdecompression segmental instability. Its
      clinical significance has not yet been clarified. MATERIALS AND METHODS: From
      2005 to 2010, 165 patients with degenerative lumbar spinal stenosis (average age:
      64.5, average follow-up: 25.8 mo) who received MEDL were reviewed. We
      investigated the incidence of PDFE with preoperative and repetitive magnetic
      resonance imaging at 6 months postoperatively. The clinical data and treatment
      courses were reviewed. The treatment outcomes were evaluated with Oswestry
      Disability Index and Japanese Orthopedic Association scores. RESULTS: The
      incidence of PDFE was 17.0% (n=28), which was significantly higher in patients
      receiving multilevel decompression and patients with scoliosis or
      spondylolisthesis. The intensity of low back pain was similar between patients
      with and without PDFE, but "mechanical" low back pain was only noted in patients
      with PDFE. Of the 28 patients with PDFE, only 9 symptomatic patients required
      invasive treatment (5 facet joint steroid injection, 3 revision MEDL, and 1
      spinal fusion). Although the postoperative Oswestry Disability Index and Japanese
      Orthopedic Association scores were significantly worse these 9 patients, the
      final outcomes were good. Progression of spondylolisthesis was noted in 2
      patients without PDFE but no patients with PDFE during the follow-up period.
      CONCLUSIONS: The relatively high incidence of PDFE after MEDL suggests that
      injury to the integrity of facet joint is inevitable during decompression of the
      stenosis, even using minimally invasive techniques. However, the overall
      stability is well preserved with very rare progression of spondylolisthesis. Most
      patients with PDFE are asymptomatic. The prognosis of PDFE is very good. Spinal
      fusion is rarely indicated.

PMID- 25075982
TI  - Bioinformatics study of cancer-related mutations within p53 phosphorylation site
      motifs.
AB  - p53 protein has about thirty phosphorylation sites located at the N- and C
      termini and in the core domain. The phosphorylation sites are relatively less
      mutated than other residues in p53. To understand why and how p53 phosphorylation
      sites are rarely mutated in human cancer, using a bioinformatics approaches, we
      examined the phosphorylation site and its nearby flanking residues, focusing on
      the consensus phosphorylation motif pattern, amino-acid correlations within the
      phosphorylation motifs, the propensity of structural disorder of the
      phosphorylation motifs, and cancer mutations observed within the phosphorylation
      motifs. Many p53 phosphorylation sites are targets for several kinases. The
      phosphorylation sites match 17 consensus sequence motifs out of the 29
      classified. In addition to proline, which is common in kinase specificity
      determining sites, we found high propensity of acidic residues to be adjacent to
      phosphorylation sites. Analysis of human cancer mutations in the phosphorylation
      motifs revealed that motifs with adjacent acidic residues generally have fewer
      mutations, in contrast to phosphorylation sites near proline residues. p53
      phosphorylation motifs are mostly disordered. However, human cancer mutations
      within phosphorylation motifs tend to decrease the disorder propensity. Our
      results suggest that combination of acidic residues Asp and Glu with
      phosphorylation sites provide charge redundancy which may safe guard against loss
      of-function mutations, and that the natively disordered nature of p53
      phosphorylation motifs may help reduce mutational damage. Our results further
      suggest that engineering acidic amino acids adjacent to potential phosphorylation
      sites could be a p53 gene therapy strategy. 

PMID- 25075988
TI  - Physical activity is associated with elevated arterial stiffness in patients with
      lumbar disk herniation.
AB  - STUDY DESIGN: A cross-sectional study in a general health examination. OBJECTIVE:
      To investigate the relationship between brachial-ankle pulse wave velocity
      (baPWV) and lumbar disk herniation (LDH). SUMMARY OF BACKGROUND DATA: Lumbar disk
      herniation (LDH) is a major cause of low back pain and sciatica. Various vascular
      risk factors such as obesity, diabetes mellitus, and smoking have been reported
      to be associated with LDH. BaPWV is an early indicator of subclinical
      atherosclerosis. METHODS: A total of 490 participants with LDH and 490
      participants without LDH were selected for the evaluation of baPWV. BaPWV was
      measured using an automatic device. The prevalence of LDH was calculated by the
      quartiles of baPWV levels. Multiple linear regression analysis was performed to
      evaluate the risk factors for baPWV. RESULTS: LDH patients had significantly
      higher readings of baPWV compared with non-LDH subjects (P<0.001). The prevalence
      rate of LDH gradually increased according to baPWV quartiles. In addition, the
      levels of baPWV tended to increase as the frequency of physical activity reduced.
      Multiple linear regression analysis showed that body mass index, low-density
      lipoprotein cholesterol, physical activity, and systolic blood pressure
      contributed to increased baPWV. CONCLUSIONS: The findings showed that LDH
      patients had higher baPWV levels. In addition, reduced physical activity was a
      risk factor contributing to increased baPWV. Further studies are warranted to
      determine the role of baPWV in LDH.

PMID- 25075987
TI  - Significance of preoperative planning simulator for junior surgeons' training of
      pedicle screw insertion.
AB  - STUDY DESIGN: A prospective study to access the significance of preoperative
      planning simulator for junior surgeons' training of pedicle screw insertion.
      SUMMARY OF BACKGROUND DATA: Pedicle screw insertion is particularly challenging
      to carry out on patients with abnormal spine morphology, especially for the
      doctors who lack experience. Currently, preoperative planning for pedicle screw
      insertion is carried out using patient computed tomography and magnetic resonance
      imaging scans. In addition, there is no projection fluoroscopy provided to the
      user. OBJECTIVE: The aim of this study was to investigate the feasibility and
      efficacy of a 3-dimensional, patient-specific volume rendering combined with the
      projection fluoroscopy simulator for training junior surgeons with no experience
      of pedicle screw insertion, and to help identify the role such simulation has in
      surgical education. METHODS: Two junior surgeons with no experience of pedicle
      screw insertion were trained on the technique through the preoperative planning
      simulator; the operative time and the position of the pedicle screws were
      assessed before training (control group 1) and after training (experimental
      group) and compared with 2 senior spine surgeons with >10 years' experience of
      pedicle screw insertion (control group 2). RESULTS: The time of per pedicle screw
      insertion was 43.5+/-3.9 seconds in control group 1, 31.6+/-2.9 seconds in
      control group 2, and 50.8+/-3.7 seconds in experimental group. The relative
      position of the screw to the pedicle was graded regarding pedicle breach (I, no
      breach; II, <2 mm; III, 2-4 mm; IV, >4 mm). The pedicle breach grading I and II
      was 20 pedicle screws (20/56, 35.7%) in control group 1, 54 pedicle screws
      (54/56, 96.4%) in control group 2, and 44 pedicle screws (44/56, 78.6%) in the
      experimental group. There were significant differences between control group 1
      and experimental group in the time of per pedicle screw insertion (P<0.001) and
      the rate of pedicle breach grading I and II (P<0.001). There were significant
      differences between control group 2 and experimental group in the time of per
      pedicle screw insertion (P<0.001) and the rate of pedicle breach grading I and II
      (P=0.004). CONCLUSIONS: The simulator offers many helpful features to the surgeon
      with respect to the surgical trainee learning the basic technique of pedicle
      screw insertion, using free-hand technique or under the guiding of intraoperative
      fluoroscopy. The surgical skills of the junior surgeons can be significantly
      improved through the training of simulator.

PMID- 25075989
TI  - The effect of hubbing on the pull-out strength of lateral mass screws in the
      cervical spine: a biomechanical experiment.
AB  - STUDY DESIGN: This was a cadaveric biomechanical experiment. OBJECTIVE: To
      compare the pull-out strength of polyaxial screws that are either hubbed or not
      hubbed when inserted into the lateral mass. SUMMARY OF BACKGROUND DATA: It has
      been shown in a study on pedicle screws in the thoracic spine that "hubbing" the
      head of the screw against the dorsal laminar cortex results in significantly
      lower pull-out strength of the screws. MATERIALS AND METHODS: Fifteen segments of
      the human cervical spine (from C3 to C7) were prepared. Polyaxial screws 3.5 mm
      in diameter were used. On one side screws 12 mm in length were inserted until the
      screw head touched the lateral mass; they were then turned 2.5 more times until
      they were fully hubbed (hubbed screws). On the other side screws 14 mm in length
      were inserted until the screw head just touched the lateral mass (nonhubbed
      screws). The 2 mm difference in length was to ensure that the screws were buried
      to the same length. All screws inserted into the lateral masses underwent tensile
      pull-out by applying a tensile force down the long axis of the screw. The
      difference in pull-out strength between the 2 groups was evaluated using a
      nonparametric paired test (the Wilcoxon signed rank test), which compared side to
      side on each vertebra. RESULTS: One specimen was excluded because of cement
      breakage during the biomechanical test. A total of 14 vertebrae were tested. Four
      vertebrae in the hubbed group showed small fractures or cracks around the screw
      hole after screw insertion. In a side to side comparison, the hubbed screws had
      significantly lower pull-out strengths as compared with the nonhubbed screws
      (P=0.033). CONCLUSIONS: Hubbing of lateral mass screws lowers the potential pull
      out strength of the screws as compared with the pull-out strength of nonhubbed
      screws. Thus, hubbing of lateral mass screws, on the basis of the parameters
      applied in this study, is not recommended.

PMID- 25075990
TI  - Expansive Laminoplasty Versus Laminectomy Alone Versus Laminectomy and Fusion for
      Cervical Ossification of the Posterior Longitudinal Ligament: Is There a
      Difference in the Clinical Outcome and Sagittal Alignment?
AB  - STUDY DESIGN: Intervention comparison study. OBJECTIVE: To assess postoperative
      cervical lordosis, clinical outcome, and progression of ossification of the
      posterior longitudinal ligament (OPLL) in patient of cervical spondylotic
      myelopathy (CSM) by the OPLL. SUMMARY OF BACKGROUND DATA: The posterior approach
      is usually used for multilevel (>=3) CSM and is decided based on cervical
      lordosis and instability. OPLL, 1 cause of CSM, makes decreased neck motion and
      is progressed by neck motion. In OPLL patients, it may be asked whether motion
      preserving surgery is still helpful. MATERIALS AND METHODS: We reviewed 57
      patients of CSM by OPLL who underwent 3 posterior surgeries, laminoplasty,
      laminectomy alone (LA), and laminectomy with fusion (LF), and followed up minimum
      24 months. Postoperative cervical sagittal balance was measured using by the C2
      C7 sagittal vertical axis (SVA), cervical curvature index, and C2-C7 Cobb angle.
      The clinical outcome was analyzed by the neck disability index and the visual
      analog scale for axial pain. OPLL progression was measured by length and depth
      growth. A linear mixed model was used to evaluate the differences between each
      time point and baseline score. RESULTS: Cervical lordosis, C2-C7 Cobb angle, and
      cervical curvature index decreased gradually in all patients. SVA was maintained
      in the LF group only and increased in the others (P=0.01). Clinical outcomes,
      neck disability index, and visual analogue scale were evenly improved in all
      groups. In patients showing SVA>=40 mm at baseline, neck pain increased in the
      laminoplasty group but was stationary in the LF group. Progression of OPLL was
      observed more frequent in the LA group than in the LF group. CONCLUSIONS:
      Posterior surgeries resulted in clinical improvements although with loss of
      cervical lordosis in CSM with OPLL patients. OPLL may worsen more frequently
      after LA. LF and laminoplasty are preferable techniques in this condition, with
      the former better for patients with high baseline SVA distances.

PMID- 25075991
TI  - Prevention of proximal junctional kyphosis after posterior surgery of Scheuermann
      kyphosis: an operative technique.
AB  - STUDY DESIGN: A prospective randomized study. OBJECTIVE: To introduce an
      operative technique that prevents proximal junctional kyphosis (PJK) in
      Scheuermann disease after a segmental posterior spinal instrumentation and
      fusion. SUMMARY OF BACKGROUND DATA: PJK is the progression of kyphotic deformity
      at the proximal end of a construct >10 degrees, and it can be seen up to 30%
      after posterior Scheuermann kyphosis surgery. After posterior fusion the
      biomechanics of the spine changes and the loss of motion at the fused levels is
      compensated by increased motion at other unfused segments. As a result
      significant amount of additional force is placed on the proximal junction. With
      our operative technique, we aimed to have a smooth passage from rigid to mobile
      segments and to decrease the stress on proximal junction during cantilever
      reduction to prevent PJK. METHODS: A total of 60 consecutive patients (mean age:
      18.27+/-3.19, male/female: 28/32) who were surgically treated for Scheuermann
      kyphosis in our institution were recruited into this study and were prospectively
      evaluated. Patients were divided into 2 groups according to upper-most screw
      fixation technique. In group 1, a standard screw insertion technique was used (ST
      group). The technique was modified in group 2 (MT group), leaving 2 threads out
      of the posterior cortex. There were 29 patients in group 1 (ST) and 31 patients
      in group 2 (MT). Patients had an average follow-up time of 24.2 months (range, 19
      48 mo). Evaluated radiographic parameters were preoperative and postoperative
      kyphosis angle, and proximal junctional angle (PJA) at last visit. PJA was
      defined as the angle between the caudal endplate of the upper instrumented
      vertebra and the cephalad endplate of 2 suprajacent vertebrae above the upper
      instrumented vertebra. PJA exceeding 10 degrees was accepted as PJK. Quality of
      life measurement was assessed preoperatively and postoperatively with SF-36
      questionnaire. RESULTS: Correction amounts in ST group and MT group were 46.8%
      and 43.7%, respectively, which was statistically insignificant. The mean PJA was
      8.08+/-2.96 degrees and 4.44+/-1.55 degrees in ST and MT groups, respectively,
      which demonstrated a statistically significant difference (P=0.001). Five
      patients in ST group had a PJA exceeding 10 degrees (PJK), whereas PJK was not
      seen in MT group (P=0.022). The improvement in physical component summary of SF
      36 was significantly better in MT group; however, mental component summary was
      similar in both groups. CONCLUSIONS: This study introduces a new technique that
      may have an effect in preventing PJK. Our results seem to be satisfactory, but
      additional studies with more patients and longer follow-up times are needed to
      further delineate the feasibility of this technique.

PMID- 25075992
TI  - Pressure distribution of intraoperative chest pad designs in patients with
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A prospective, comparative study. OBJECTIVE: To evaluate the
      resultant force and pressure distribution between chest pad designs for scoliosis
      patients while in the prone position. SUMMARY OF BACKGROUND DATA: Scoliosis
      affects the anatomy of the lungs and the chest wall, which can adversely affect
      pulmonary function. Scoliosis surgery requires that patients remain prone for
      several hours with their body weight supported by pads under the chest and
      pelvis. As a significant portion of the patient's weight is on the chest, this
      extrinsic pressure may further affect the pulmonary status of already compromised
      lungs. METHODS: Fourteen female subjects with right main thoracic adolescent
      idiopathic scoliosis of at least 45 degrees were evaluated. A Jackson Spinal
      Surgery and Imaging Table (Orthopaedic Systems Inc.) was used with commercially
      available (Vista Medical) pressure transducer mats that were overlaid on the
      chest and hip supports. Awake subjects were positioned on the table during 2
      testing conditions: 1 chest pad versus 2 chest pads on the table. Over a 60
      second testing period for each condition, the average and maximum pressures and
      resultant force were found for each pad. RESULTS: The 1 and 2 pad systems had
      average chest pressures of 4.51+/-1.07 versus 3.10+/-0.64 kPa (P<0.05), and
      maximum chest pressures of 12.9+/-3.1 versus 9.44+/-3.14 kPa (P<0.05). The 1 and
      2 pad systems had average pelvic pressures of 2.67+/-0.57 versus 2.98+/-0.56 kPa
      (P<0.05), and maximum pelvic pressures of 15.1+/-7.8 versus 19.4+/-0.8 kPa
      (P<0.05). CONCLUSIONS: The 2 pad chest support system resulted in lower maximum
      and average pressures at the chest and higher maximum and average pressures at
      the pelvis as compared with the 1 pad design.

PMID- 25075994
TI  - Time to development, clinical and radiographic characteristics, and management of
      proximal junctional kyphosis following adult thoracolumbar instrumented fusion
      for spinal deformity.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: To study time to development,
      clinical and radiographic characteristics, and management of proximal junctional
      kyphosis (PJK) following thoracolumbar instrumented fusion for adult spinal
      deformity (ASD). SUMMARY OF BACKGROUND DATA: PJK continues to be a common mode of
      failure following ASD surgery. Although literature exists on possible risk
      factors, data on management remain limited. METHODS: A retrospective review of
      medical records of 289 consecutive ASD patients who underwent posterior segmental
      instrumentation incorporating at least 5 segments was conducted. PJK was defined
      as proximal kyphotic angle >10 degrees. RESULTS: PJK occurred in 32 patients
      (11%) at a mean follow-up of 34 months (range, 1.3-61.9+/-19 mo). Sixteen (50%)
      patients were revised (mean, 1.7 revisions; range, 1-3) at a mean follow-up of
      9.6 months (range, 0.7-40 mo); primary indications for revision were pain (n=16),
      myelopathy (n=6), instability (n=4), and instrumentation protrusion (n=2).
      Comparison of preindex and postindex surgery radiographic parameters demonstrated
      significant improvement in mean lumbar lordosis (24 vs. 42 degrees, P<0.001),
      pelvic incidence-lumbar lordosis mismatch (30 vs. 11 degrees, P<0.001), and
      pelvic tilt (29 vs. 23 degrees, P<0.011). The mean T5-T12 kyphosis worsened (30
      vs. 53 degrees, P<0.001) and the mean global sagittal spinal alignment failed to
      improve (9.6 vs. 8.0 cm, P=0.76). There was no apparent relationship between the
      absolute PJK angle and revision surgery (P>0.05). CONCLUSIONS: The patients in
      this series who developed PJK had substantial preoperative positive sagittal
      malalignment that remained inadequately corrected following surgery, likely
      resulting from a combination of inadequate surgical correction and a significant
      compensatory increase in thoracic kyphosis. In the absence of direct relationship
      between a greater PJK angle and worse clinical outcome, clinical symptoms and
      neurological status rather than absolute reliance on radiographic parameters
      should drive the decision to pursue revision surgery.

PMID- 25075995
TI  - [Costs of a guideline-based treatment of patients with chronic hepatitis C in
      Germany].
AB  - The costs of a guideline-based treatment in chronic hepatitis C infected people
      are unknown. The goal of HCV therapy is to achieve a sustained viral response and
      thereby to reduce morbidity and mortality due to complications of liver cirrhosis
      and hepatocellular carcinoma. This study analyses the costs of a guideline-based
      treatment based on the German guideline on the management of HCV infection. In
      addition, costs of newly introduced protease inhibitors were calculated. Costs
      for baseline diagnostics, monitoring and medical treatment were calculated
      according to the stage of the disease, the HCV genotype and viral response. Costs
      for baseline diagnostics account for ? 302.75 and monitoring accounts for ? 596
      to ? 1173. Dual therapy with pegylated interferon and ribavirin results in
      average costs of ? 7709 to ? 34 692. Total costs of a guideline-based treatment
      range between ? 8,608 and ? 36 167 depending on HCV genotype and length of
      therapy. With the introduction of protease inhibitors for HCV genotype 1
      patients, costs of pharmaceuticals have increased further. Triple-therapy with
      telaprevir accounts for ? 43 280 respectively ? 54 844. Costs for Boceprevir
      treatment range from ? 34 143 to ? 60 990. Due to increasing costs, health
      economic evaluations gain significant relevance and should be considered when
      implementing new treatment strategies. 

PMID- 25075996
TI  - Losing a language in childhood: a longitudinal case study on language attrition.
AB  - This paper is based upon a longitudinal study of L2 attrition in a bilingual
      child who grew up in an L2 migration background (Germany) and moved to the
      country of origin (Portugal) at the age of nine, experiencing a dominance shift
      from the L2 to the L1. The study aims to analyze the effects of language loss in
      L2 German. Data collection started 3 weeks after the child's immersion in the
      Portuguese setting and ended 18 months later. Results show first effects of
      language attrition after 5 months of reduced exposure to German; 18 months later
      the informant showed severe word retrieval difficulties and was unable to produce
      complete sentences in her L2. The findings thus confirm the conclusions of other
      studies on child language attrition, which attest to strong effects of attrition
      when the loss of contact with the target language occurs in childhood. 

PMID- 25075997
TI  - Positive supercoiling affiliated with nucleosome formation repairs non-B DNA
      structures.
AB  - It is demonstrated that positive supercoiling affiliated with nucleosome
      formation can act as the driving force to repair the G-quadruplex, cruciform as
      well as a stable non-B DNA structure caused by peptide nucleic acid. 

PMID- 25075998
TI  - Assessment of the measurement properties of quality of life questionnaires in
      Brazilian women with breast cancer.
AB  - BACKGROUND: There are several questionnaires available to assess quality of life
      in breast cancer, however the choice of the best questionnaire often does not
      take into account the adequacy of these questionnaires' measurement properties.
      OBJECTIVE: To test the measurement properties of two generic quality of life
      questionnaires and one quality of life questionnaire specific for women with
      breast cancer. METHOD: We assessed 106 women after surgery for breast cancer. The
      assessment included application of the SF-36, WHOQOL-bref, and FACT-B+4
      questionnaires as well as the Global Perceived Effect and Pain Numerical Rating
      scales. The participants were interviewed on three occasions to investigate
      internal consistency, floor and ceiling effects, construct validity,
      reproducibility, and responsiveness. RESULTS: Most of the instruments' domains
      showed adequate internal consistency (Cronbach's alpha varying from 0.66 to
      0.91). Reliability varied from poor to substantial (ICC2,1 between 0.39 and 0.87)
      and agreement varied from negative to very good. The SF-36 presented doubtful
      agreement and showed floor and ceiling effects in three domains. The domains of
      the generic questionnaires presented moderate to good correlation with the FACT
      B+4 (Pearson varying from 0.31 to 0.69). The internal responsiveness varied from
      small to large (ES varying from -0.26 to 0.98) and external responsiveness was
      found in only some of the instruments' domains. CONCLUSIONS: Most of the
      measurement properties tested for the WHOQOL-bref and FACT-B+4 were adequate as
      was their ability to assess quality of life in women with breast cancer. The SF
      36 showed inadequacy in agreement and floor and ceiling effects and should not be
      used in women with breast cancer.

PMID- 25075999
TI  - Respiratory pattern of diaphragmatic breathing and pilates breathing in COPD
      subjects.
AB  - BACKGROUND: Diaphragmatic breathing (DB) is widely used in pulmonary
      rehabilitation (PR) of patients with chronic obstructive pulmonary disease
      (COPD), however it has been little studied in the scientific literature. The
      Pilates breathing (PB) method has also been used in the rehabilitation area and
      has been little studied in the scientific literature and in COPD. OBJECTIVES: To
      compare ventilatory parameters during DB and PB in COPD patients and healthy
      adults. METHOD: Fifteen COPD patients (COPD group) and fifteen healthy patients
      (healthy group) performed three types of respiration: natural breathing (NB), DB,
      and PB, with the respiratory pattern being analyzed by respiratory inductive
      plethysmography. The parameters of time, volume, and thoracoabdominal
      coordination were evaluated. After the Shapiro-Wilk normality test, ANOVA was
      applied followed by Tukey's test (intragroup analysis) and Student's t-test
      (intergroup analysis; p<0.05). RESULTS: DB promoted increase in respiratory
      volumes, times, and SpO2 as well as decrease in respiratory rate in both groups.
      PB increased respiratory volumes in healthy group, with no additional benefits of
      respiratory pattern in the COPD group. With respect to thoracoabdominal
      coordination, both groups presented higher asynchrony during DB, with a greater
      increase in the healthy group. CONCLUSIONS: DB showed positive effects such as
      increase in lung volumes, respiratory motion, and SpO2 and reduction in
      respiratory rate. Although there were no changes in volume and time measurements
      during PB in COPD, this breathing pattern increased volumes in the healthy
      subjects and increased oxygenation in both groups. In this context, the acute
      benefits of DB are emphasized as a supporting treatment in respiratory
      rehabilitation programs.

PMID- 25076000
TI  - Sensory processing abilities of children with ADHD.
AB  - OBJECTIVE: To assess and compare the sensory processing abilities of children
      with Attention Deficit/Hyperactivity Disorder (ADHD) and children without
      disabilities, and to analyze the relationship between sensory processing
      difficulties and behavioural symptoms presented by children with ADHD. METHOD:
      Thirty-seven children with ADHD were compared with thirty-seven controls using a
      translated and adapted version of the "Sensory Profile" answered by the
      parents/caregivers. For the ADHD group, Sensory Profile scores were correlated to
      behavioural symptoms assessed using the Child Behaviour Check List (CBCL) and the
      Behavioural Teacher Rating Scale (EACI-P). The statistical analyses were
      conducted using the Mann Whitney test and Pearson correlation coefficients.
      RESULTS: Children with ADHD showed significant impairments compared to the
      control group in sensory processing and modulation, as well as in behavioural and
      emotional responses as observed in 11 out of 14 sections and 6 out of 9 factors.
      Differences in all Sensory Profile response patterns were also observed between
      the two groups of children. Sensory Profile scores showed a moderately negative
      correlation with CBCL and EACI-P scores in the ADHD group. CONCLUSION: These
      results indicate that children with ADHD may present sensory processing
      impairments, which may contribute to the inappropriate behavioural and learning
      responses displayed by children with ADHD. It also suggests the importance of
      understanding the sensory processing difficulties and its possible contribution
      to the ADHD symptomatology.

PMID- 25076001
TI  - Balance and muscle power of children with Charcot-Marie-Tooth.
AB  - BACKGROUND: In certain diseases, functional constraints establish a greater
      relationship with muscle power than muscle strength. However, in hereditary
      peripheral polyneuropathies, no such relationship was found in the literature.
      OBJECTIVE: In children with Charcot-Marie-Tooth (CMT), to identify the impact of
      muscle strength and range of movement on the static/dynamic balance and standing
      long jump based on quantitative and functional variables. METHOD: The study
      analyzed 19 participants aged between 6 and 16 years, of both genders and with
      clinical diagnoses of CMT of different subtypes. Anthropometric data, muscle
      strength of the lower limbs (hand-held dynamometer), ankle and knee range of
      movement, balance (Pediatric Balance Scale) and standing long jump distance were
      obtained by standardized procedures. For the statistical analysis, Pearson and
      Spearman correlation coefficients were used. RESULTS: There was a strong positive
      correlation between balance and the muscle strength of the right plantar flexors
      (r=0.61) and dorsiflexors (r=0.59) and a moderate correlation between balance and
      the muscle strength of inversion (r=0.41) and eversion of the right foot
      (r=0.44). For the long jump and range of movement, there was a weak positive
      correlation with right and left plantar flexion (r=0.20 and r=0.12, respectively)
      and left popliteal angle (r=0.25), and a poor negative correlation with left
      dorsiflexion (r=-0.15). CONCLUSIONS: The data on the patients analyzed suggests
      that the maintenance of distal muscle strength favors performance during balance
      tasks, while limitations in the range of movement of the legs seem not to be
      enough to influence the performance of the horizontal long jump.

PMID- 25076003
TI  - Novel EDTA-ligands containing an integral perylene bisimide (PBI) core as an
      optical reporter unit.
AB  - The synthesis, characterization and metal complexation of a new class of perylene
      bisimides (PBIs) as an integral part of ethylenediaminetetraacetic acid (EDTA)
      are reported. The simplest representative, namely derivative 1a, was synthesized
      both by a convergent as well as a direct approach while the elongated
      derivatives, 1b and 1c, were obtained only via a convergent synthetic pathway.
      All these new prototypes of water-soluble perylenes are bolaamphiphiles and were
      fully characterized by (1)H- and (13)C-NMR spectroscopy, matrix assisted laser
      desorption ionization-time of flight (MALDI-TOF) mass spectrometry and IR
      spectroscopy. In order to acquaint ourselves with the behaviour in solution of
      our PBIs bearing dendritic wedges, the simplest derivative, 1a, was chosen and
      tested by means of UV/Vis and fluorescence spectroscopy as well as by zeta
      potential measurements. A photoexcitation induced intramolecular photo-electron
      transfer (PET) can be observed in these molecules. Therefore their potential
      applications as sensors can be imagined. Model compound 1a efficiently
      coordinates trivalent metal cations both in water and dimethyl sulfoxide (DMSO).
      Significantly, the effects of the complexation strongly depend on the aggregation
      state of the PBI molecules in solution. As a matter of fact, in water, the
      presence of M(3+) ions triggers the formation of light emitting supramolecular
      aggregates (excimers). On the other hand, in DMSO-rich solutions metal
      complexation leads to the suppression of the PET and leads to a strong
      fluorescence enhancement.

PMID- 25076002
TI  - Effect of low-level laser therapy on the modulation of the mitochondrial activity
      of macrophages.
AB  - BACKGROUND: Macrophages play a major role among the inflammatory cells that
      invade muscle tissue following an injury. Low-level laser therapy (LLLT) has long
      been used in clinical practice to accelerate the muscle repair process. However,
      little is known regarding its effect on macrophages. OBJECTIVE: This study
      evaluated the effect of LLLT on the mitochondrial activity (MA) of macrophages.
      METHOD: J774 macrophages were treated with lipopolysaccharide (LPS) and
      interferon - gamma (IFN-gamma) (activation) for 24 h to simulate an inflammatory
      process, then irradiated with LLLT using two sets of parameters (780 nm; 70 mW; 3
      J/cm2 and 660 nm; 15 mW; 7.5 J/cm2). Non-activated/non-irradiated cells composed
      the control group. MA was evaluated by the cell mitochondrial activity (MTT)
      assay (after 1, 3 and 5 days) in three independent experiments. The data were
      analyzed statistically. RESULTS: After 1 day of culture, activated and 780 nm
      irradiated macrophages showed lower MA than activated macrophages, but activated
      and 660 nm irradiated macrophages showed MA similar to activated cells. After 3
      days, activated and irradiated (660 nm and 780 nm) macrophages showed greater MA
      than activated macrophages, and after 5 days, the activated and irradiated (660
      nm and 780 nm) macrophages showed similar MA to the activated macrophages.
      CONCLUSIONS: These results show that 660 nm and 780 nm LLLT can modulate the
      cellular activation status of macrophages in inflammation, highlighting the
      importance of this resource and of the correct determination of its parameters in
      the repair process of skeletal muscle.

PMID- 25076005
TI  - Data-driven subclassification of speech sound disorders in preschool children.
AB  - PURPOSE: The purpose of the study was to determine whether distinct subgroups of
      preschool children with speech sound disorders (SSD) could be identified using a
      subgroup discovery algorithm (SUBgroup discovery via Alternate Random Processes,
      or SUBARP). Of specific interest was finding evidence of a subgroup of SSD
      exhibiting performance consistent with atypical speech motor control. METHOD:
      Ninety-seven preschool children with SSD completed speech and nonspeech tasks.
      Fifty-three kinematic, acoustic, and behavioral measures from these tasks were
      input to SUBARP. RESULTS: Two distinct subgroups were identified from the larger
      sample. The 1st subgroup (76%; population prevalence estimate = 67.8%-84.8%) did
      not have characteristics that would suggest atypical speech motor control. The
      2nd subgroup (10.3%; population prevalence estimate = 4.3%-16.5%) exhibited
      significantly higher variability in measures of articulatory kinematics and poor
      ability to imitate iambic lexical stress, suggesting atypical speech motor
      control. Both subgroups were consistent with classes of SSD in the Speech
      Disorders Classification System (SDCS; Shriberg et al., 2010a). CONCLUSION:
      Characteristics of children in the larger subgroup were consistent with the
      proportionally large SDCS class termed speech delay; characteristics of children
      in the smaller subgroup were consistent with the SDCS subtype termed motor speech
      disorder-not otherwise specified. The authors identified candidate measures to
      identify children in each of these groups.

PMID- 25076006
TI  - Modeling the repair of DNA strand breaks caused by gamma-radiation in a
      minichromosome.
AB  - The objective of the studies described here was the development of a mathematical
      model which would fit experimental data for the repair of single and double
      strand breaks induced in DNA in living cells by exposure to ionizing radiation,
      and which would allow to better understand the processes of DNA repair. DNA
      breaks are believed to play the major role in radiation-induced lethality and
      formation of chromosome deletions, and are therefore crucial to the response of
      cells to radiotherapy. In an initial model which we reported on the basis of data
      for the repair of Epstein-Barr minichromosomes in irradiated Raji cells, we
      assumed that DNA breaks are induced only at the moment of irradiation and are
      later removed by repair systems. This work gives a development of that
      mathematical model which fits the experimental results more precisely and
      suggests strongly that DNA breaks are generated not only by direct irradiation
      but also later, probably by systems engaged in repair of oxidative damage. 

PMID- 25076007
TI  - Prehabilitation versus rehabilitation: a randomized control trial in patients
      undergoing colorectal resection for cancer.
AB  - BACKGROUND: The preoperative period (prehabilitation) may represent a more
      appropriate time than the postoperative period to implement an intervention. The
      impact of prehabilitation on recovery of function al exercise capacity was thus
      studied in patients undergoing colorectal resection for cancer. METHODS: A
      parallel-arm single-blind superiority randomized controlled trial was conducted.
      Seventy-seven patients were randomized to receive either prehabilitation (n = 38)
      or rehabilitation (n = 39). Both groups received a home-based intervention of
      moderate aerobic and resistance exercises, nutritional counseling with protein
      supplementation, and relaxation exercises initiated either 4 weeks before surgery
      (prehabilitation) or immediately after surgery (rehabilitation), and continued
      for 8 weeks after surgery. Patients were managed with an enhanced recovery
      pathway. Primary outcome was functional exercise capacity measured using the
      validated 6-min walk test. RESULTS: Median duration of prehabilitation was 24.5
      days. While awaiting surgery, functional walking capacity increased (>= 20 m) in
      a higher proportion of the prehabilitation group compared with the rehabilitation
      group (53 vs. 15%, adjusted P = 0.006). Complication rates and duration of
      hospital stay were similar. The difference between baseline and 8-week 6-min
      walking test was significantly higher in the prehabilitation compared with the
      rehabilitation group (+23.7 m [SD, 54.8] vs. -21.8 m [SD, 80.7]; mean difference
      45.4 m [95% CI, 13.9 to 77.0]). A higher proportion of the prehabilitation group
      were also recovered to or above baseline exercise capacity at 8 weeks compared
      with the rehabilitation group (84 vs. 62%, adjusted P = 0.049). CONCLUSION:
      Meaningful changes in postoperative functional exercise capacity can be achieved
      with a prehabilitation program.

PMID- 25076009
TI  - Indeterminate left-sided retroperitoneal mass.

PMID- 25076008
TI  - Extreme pain from brown recluse spider bites: model for cytokine-driven pain.
AB  - IMPORTANCE: Bites from the brown recluse spider (BRS) can cause extreme pain. We
      propose cytokine release as a cause of the discomfort and a central mechanism
      through glial cell upregulation to explain measured pain levels and time course.
      OBSERVATIONS: Twenty-three BRS bites were scored at a probable or documented
      level clinically, and an enzyme-linked immunosorbent assay was used to confirm
      the presence of BRS venom. The mean (SD) pain level in these cases 24 hours after
      the spider bite was severe: 6.74 (2.75) on a scale of 0 to 10. Narcotics may be
      needed to provide relief in some cases. The difference in pain level by anatomic
      region was not significant. Escalation observed in 22 of 23 cases, increasing
      from low/none to extreme within 24 hours, is consistent with a cytokine pain
      pattern, in which pain increases concomitantly with a temporal increase of
      inflammatory cytokines. CONCLUSIONS AND RELEVANCE: These findings in BRS bites
      support the hypothesis of cytokine release in inflammatory pain. A larger series
      is needed to confirm the findings reported here. The extreme pain from many BRS
      bites motivates us to find better prevention and treatment techniques.

PMID- 25076011
TI  - Gaining biological perspectives from schistosome genomes.
AB  - Characterization of the genomic basis underlying schistosome biology is an
      important strategy for the development of future treatments and interventions.
      Genomic sequence is now available for the three major clinically relevant
      schistosome species, Schistosoma mansoni, S. japonicum and S. haematobium, and
      this information represents an invaluable resource for the future control of
      human schistosomiasis. The identification of a biologically important, but
      distinct from the host, schistosome gene product is the ultimate goal for many
      research groups. While the initial elucidation of the genome of an organism is
      critical for most biological research, continued improvement or curation of the
      genome construction should be an ongoing priority. In this review we will discuss
      prominent recent findings utilizing a systems approach to schistosome biology, as
      well as the increased use of interference RNA (RNAi). Both of these research
      strategies are aiming to place parasite genes into a more meaningful biological
      perspective. 

PMID- 25076012
TI  - Surrogate measures for providing high frequency estimates of total phosphorus
      concentrations in urban watersheds.
AB  - Until robust in situ sensors for total phosphorus (TP) are developed, continuous
      water quality measurements have the potential to be used as surrogates for
      generating high frequency estimates. Their use has widespread implications for
      water quality monitoring programmes considering that TP, in particular, is
      generally recognised as the limiting factor in the process of eutrophication.
      Surrogate measures for TP concentration, such as turbidity, have proved useful
      within natural and agricultural contexts, but their predictive capability for
      urban watersheds is considered more difficult, due to the different sources of
      TP, though a strict relationship with turbidity/suspended matter has been clearly
      described even for these environments. In this context, we investigated this
      still unresolved problem for high frequency estimation of TP concentration in
      urban environments by monitoring a medium-sized (71 km(2)) urban watershed
      (Lambro River watershed, north Italy) in which we detected 60 active combined
      sewer overflows, and an its natural sub-basin for comparison. We found two
      different relationships between turbidity and TP concentration in the
      investigated urban watershed that differently describe the prevalence of TP from
      point sources (domestic wastewaters) or diffuse origin (surface runoff). In this
      regard, we first characterise the prevailing sources of TP by using a marker for
      detecting domestic wastewater contamination (caffeine), then we describe the
      mutual relationships amongst the continuously monitored variables (in our case
      the occurrence of the First Flush and the clockwise turbidity/discharge
      hysteresis). Afterwards we discriminate, by observing variables that are
      continuously monitored (in our case, the discharge and the turbidity), amongst
      the continuous surrogate records according to their sources. In conclusion, we
      are able to apply the relevant turbidity/TP regression equations to each
      turbidity record and, thus, estimate the respective TP concentrations with high
      frequency. If traditional grab sampling techniques had been employed, the
      contributions of point sources (up to 34% across 237 monitored days) to the total
      estimated loads would not have been correctly evaluated, whilst the high
      frequency monitoring is able to catch the dynamics that occur over time scales of
      a few hours. We conclude that the reasonable uncertainty obtained in this study
      can be achieved in other urban watersheds, but further studies are required for
      watersheds of differing sizes and degrees of urbanisation. 

PMID- 25076013
TI  - The flavonoid quercetin induces acute vasodilator effects in healthy volunteers:
      correlation with beta-glucuronidase activity.
AB  - Quercetin exerts vasodilator, antiplatelet and antiproliferative effects and
      reduces blood pressure, oxidative status and end-organ damage in hypertensive
      humans and animal models. We hypothesized that oral quercetin might induce
      vasodilator effects in humans and that they might be related to the deconjugation
      of quercetin-3-O-glucuronide (Q3GA). DESIGN: double blind, randomized, placebo
      controlled trial. Fifteen healthy volunteers (26+/-5 years, 6 female) were given
      a capsule containing placebo, 200 or 400mg of quercetin in random order in three
      consecutive weeks. At 2h a dose-dependent increase in Q3GA was observed in plasma
      (~0.4 and 1MUM for 200 and 400mg, respectively) with minor levels of quercetin
      and isorhamnetin. No changes were observed in blood pressure. At 5h quercetin
      induced and increase in brachial arterial diameter that correlated with the
      product of the levels of Q3GA by the plasma glucuronidase activity. There was an
      increase in urinary levels of glutathione but there was no increase in nitrites
      plus nitrates. Quercetin and isorhamnetin also relaxed human umbilical arteries
      in vitro while Q3GA was without effect. In conclusions, quercetin exerts acute
      vasodilator effects in vivo in normotensive, normocholesterolemic human subjects.
      These results are consistent with the effects being due to the deconjugation of
      the metabolite Q3GA.

PMID- 25076014
TI  - Isolation of Rickettsia typhi from human, Mexico.

PMID- 25076015
TI  - Importance of dam BW change and calf birth weight in double-muscled Belgian Blue
      cattle and its relationship with parity and calving interval.
AB  - Factors affecting calving interval (CI) in double-muscled Belgian Blue (DMBB)
      beef cows were investigated with regard to the BW yield (BWY) of the cow-calf
      pair, using 834 CI records from 386 females with parities 1 to 6. The effect of
      parity and CI on BWY was also studied. Cow-calf pair BWY was defined as calf
      birth weight plus dam BWY per CI. CI (mean+/-s.e.: 404+/-1.9 days) was affected
      by parity, calving season, suckling and calf birth weight/dam weight. Primiparous
      cows had a shorter CI than cows with three or more calvings (P<0.05), with an
      intermediate CI for second-calf cows. Spring calvings resulted in a shorter CI
      than summer and autumn calvings, with intermediate values for winter calvings.
      Suckling dams had longer CIs than non-suckling dams. There were interactions
      (P<0.05) between calving season and suckling, and between calving season and
      mating system. Shortest CIs were observed for spring calvings in case of non
      suckling and for summer calvings in case of suckling. Longest CIs were observed
      for autumn calvings in case of natural service (NS) and for winter calvings in
      case of artificial insemination (AI). Calf birth weight/dam weight of 6% to 10%
      resulted in shorter CI than a ratio of <6% (P<0.05). Body condition and mating
      system (NS v. AI) did not affect CI. Daily cow-calf pair BWY was affected by
      parity (P<0.001) and CI (P=0.013), with a tendency for an interaction (P=0.094).
      Daily cow-calf pair BWY did not differ for CIs of <12 to 16 months in primiparous
      cows and was lowest for a CI of 13 to 15 months in second-calf cows, whereas the
      effect of CI was more variable in older cows. Dam contribution to cow-calf pair
      BWY was larger than calf birth weight in first- and second-calf cows, and
      increased with increasing CI. Dam contribution to cow-calf pair BWY was smaller
      than calf birth weight in older cows, varying from 0.2 to 1.0 depending on CI. A
      short CI is advised for DMBB cows because of a larger BWY and more efficient
      nutrient utilisation. 

PMID- 25076016
TI  - Commissions and omissions are dissociable aspects of everyday action impairment
      in schizophrenia.
AB  - Prior research using performance-based assessment of functional impairment has
      informed a novel neuropsychological model of everyday action impairment in
      dementia in which omission errors (i.e., failure to complete task steps)
      dissociate from commission errors (i.e., inaccurate performance of task steps)
      and have unique neuropsychological correlates. However, this model has not been
      tested in other populations. The present study examined whether this model
      extends to schizophrenia. Fifty-four individuals with schizophrenia or
      schizoaffective disorder were administered a neuropsychological protocol and the
      Naturalistic Action Test (NAT), a performance-based measure of everyday action. A
      principal component analysis (PCA) was performed to examine the construct(s)
      comprising everyday action impairment, and correlations between the resultant
      component(s) and neuropsychological tests were examined. Results showed that
      omissions and a subset of commissions were distinct components of everyday
      action. However, results did not support unique associations between these
      components and specific neuropsychological measures. These findings extend the
      omission-commission model to schizophrenia and may have important implications
      for efficient assessment and effective rehabilitation of functional impairment,
      such as the potential efficacy of targeted interventions for the rehabilitation
      of omission and commission deficits in everyday functioning. Larger studies with
      prospective designs are needed to replicate the present preliminary findings.

PMID- 25076017
TI  - Charcot arthropathy of the elbow joint as a presenting feature of Chiari
      malformation with syringomyelia.
AB  - Charcot arthropathy of the elbow joint is occasionally seen with Chiari
      malformation with syringomyelia, but rarely as a presenting feature as in the
      reported case. The treatment is directed toward its underlying cause to halt its
      progression. Thus, it is important to diagnose the cause as early as possible.

PMID- 25076019
TI  - Evaluation of clinical pharmacy services offered for palliative care patients in
      Qatar.
AB  - Palliative care is an emerging concept in the countries of the Gulf Cooperation
      Council, a political and economic union of Arab states bordering the Persian
      Gulf, namely Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab
      Emirates. Clinical pharmacy services have not yet been evaluated in this region.
      The objectives of this study were to create a baseline inventory of clinical
      pharmacy interventions in palliative care and to assess the perceived importance
      of interventions made. This was a prospective, single-center characterization
      study. Interventions were documented from September 30 to December 1, 2013. They
      were characterized into predetermined categories and analyzed using descriptive
      statistics. Physician acceptance rate and intervention rate per patient were
      calculated. Classification categories were sent to 10 practicing pharmacists in
      each of Qatar and Canada, who ranked the categories on the basis of perceived
      importance. A total of 96 interventions were documented, giving 3 interventions
      per patient and an acceptance rate of 81%. Discontinuing therapy (29%),
      initiating therapy (25%), and provision of education/counseling (13.5%) were most
      common. No differences were found between rankings from pharmacists in Qatar or
      Canada. Clinical pharmacy interventions are frequent, and those relating to
      alterations in drug therapy are most common. Interventions align with the
      perceived importance from pharmacists in both Qatar and Canada.

PMID- 25076018
TI  - Self-assembly of prevascular tissues from endothelial and fibroblast cells under
      scaffold-free, nonadherent conditions.
AB  - To advance the emerging field of bioengineered prevascularized tissues, we
      investigated factors that control primary vascular network formation in scaffold
      free, high-density cell suspension-derived tissues. Fabricating primary vascular
      networks in a scaffold-free system requires endothelial cells (ECs) and
      extracellular matrix (ECM)-producing cells that act together to elaborate a
      permissive matrix. We report findings on the effects to vascular patterning
      induced by altering the ratio of human endothelial to human fibroblast cells.
      Analysis revealed that a 1:4 ratio of ECs to fibroblasts resulted in the
      synthesis of an ECM permissive for organization of primary vascular networks that
      recapitulated the pattern of primary vascular networks observed in vivo.
      Importantly this work highlighted the significance of tension in the organization
      of vascular networks in prevascularized tissues. To our knowledge our in vitro
      studies are the first to demonstrate the formation of two distinct vascular
      patterns in an initially homogenous culture system. Specifically, we demonstrate
      that within our constructs, vascular networks formed with distinct directional
      orientations that reflect self-assembly-mediated tension. Further, our studies
      demonstrate that treatment of prevascularized tissues with matrix-promoting
      factors such as transforming growth factor beta 1 (TGFbeta1) increases tissue
      strength without altering vascular network patterning. Together, the ability to
      generate prevascularized tissues from human cells in scaffold-free systems and
      the ability to enhance the strength of the constructs with matrix-promoting
      factors represent advances to the potential translational utility of
      prevascularized tissues both as subcutaneous implants and in surgical scenarios
      requiring the application of tension to the tissue construct. 

PMID- 25076020
TI  - French translation and validation of the Readiness for Interprofessional Learning
      Scale (RIPLS) in a Canadian undergraduate healthcare student context.
AB  - The Canadian Interprofessional Health Collaborative recommends that future
      professionals be prepared for collaborative practice. To do so, it is necessary
      for them to learn about the principles of interprofessional collaboration.
      Therefore, to ascertain if students are predisposed, their attitude toward
      interprofessional learning must be assessed. In the French Canadian context such
      a measuring tool has not been published yet. The purpose of this study is to
      translate in French an adapted version of the RIPLS questionnaire and to validate
      it for use with undergraduate students from seven various health and social care
      programmes in a Canadian university. According to Vallerand's methodology, a
      method for translating measuring instruments: (i) the forward-backward
      translation indicated that six items of the experimental French version of the
      RIPLS needed to be more specific; (ii) the experimental French version of the
      RIPLS seemed clear according to the pre-test assessing items clarity; (iii)
      evaluation of the content validity indicated that the experimental French version
      of the RIPLS presents good content validity and (iv) a very good internal
      consistency was obtained (alpha = 0.90; n = 141). Results indicate that the
      psychometric properties of the RIPLS in French are comparable to the English
      version, although a different factorial structure was found. The relevance of
      three of the 19 items on the RIPLS scale is questionable, resulting in a revised
      16-item scale. Future research aimed at validating the translated French version
      of the RIPLS could also be conducted in another francophone cultural context.

PMID- 25076021
TI  - Partnering to provide simulated learning to address Interprofessional Education
      Collaborative core competencies.
AB  - Learning to effectively communicate and work with other professionals requires
      skill, yet interprofessional education is often not included in the undergraduate
      healthcare provider curriculum. Simulation is an effective pedagogy to bring
      students from multiple professions together for learning. This article describes
      a pilot study where nursing and social work students learned together in a
      simulated learning activity, which was evaluated to by the Readiness for
      Interprofessional Learning Scale (RIPLS). The RIPLS was used before and after the
      simulated activity to determine if this form of education impacted students'
      perceptions of readiness to learn together. Students from both professions
      improved in their RIPLS scores. Students were also asked to identify their
      interprofessional strengths and challenges before and after the simulation.
      Changes were identified in qualitative data where reports of strengths and
      challenges indicated learning and growth had occurred. In conclusion, this pilot
      study suggests that interprofessional simulation can be an effective method to
      integrate Interprofessional Education Collaborative core competencies into the
      curriculum. 

PMID- 25076023
TI  - Model-Guided Flapless Immediate Implant Placement and Provisionalization in the
      Esthetic Zone Utilizing a Nanostructured Titanium Implant: A Case Report.

PMID- 25076022
TI  - Ultra-performance liquid chromatography/quadrupole-time-of-flight mass
      spectrometry analysis of icariside II metabolites in rats.
AB  - The possible metabolic pathways of icariside II were proposed. An ultra
      performance liquid chromatography/quadrupole-time-of-flight mass spectrometry
      method was used for analysing the faecal, bile, plasma and urine samples of rats
      administrated with icariside II. In all, 27 metabolites were identified in the
      biosamples. Of these, 20, including F1-F12, D3, D4, D6, D7-D9 and M3, M4, were,
      to our knowledge, reported for the first time. The results indicated that
      icariside II was metabolised via desugarisation, dehydrogenation, hydrogenation,
      hydroxylation, demethylation, glucuronidation, dehydration and glycosylation
      pathways in vivo. Specific hydrolysis of 7-O glucosides in the gut lumen and
      glucuronic acid conjugation in the liver were considered as the main physiologic
      processes of icariside II. This study revealed the possible metabolite profiles
      of icariside II in rats. 

PMID- 25076024
TI  - Chest Compression Injuries Detected via Routine Post-arrest Care in Patients Who
      Survive to Admission after Out-of-hospital Cardiac Arrest.
AB  - Abstract Objective. To examine injuries produced by chest compressions in out-of
      hospital cardiac arrest (OHCA) patients who survive to hospital admission.
      Methods. A retrospective cohort study was conducted among 235 consecutive
      patients who were hospitalized after nontraumatic OHCA in Minnesota between
      January 2009 and May 2012 (117 survived to discharge; 118 died during
      hospitalization). Cases were eligible if the patient had received prehospital
      compressions from an emergency medical services (EMS) provider. One EMS provider
      in the area was using a mechanical compression device (LUCASTM) as standard
      equipment, so the association between injury and use of mechanical compression
      was also examined. Prehospital care information was abstracted from EMS run
      sheets, and hospital records were reviewed for injuries documented during the
      post-arrest hospitalization that likely resulted from compressions. Results.
      Injuries were identified in 31 patients (13%), the most common being rib fracture
      (9%) and intrathoracic hemorrhage (3%). Among those who survived to discharge,
      the mean length of stay was not statistically significantly different between
      those with injuries (13.5 days) and those without (10.8 days; p = 0.23). Crude
      injury prevalence was higher in those who died prior to discharge, had received
      compressions for >10 minutes (versus <=10 minutes) and underwent computer
      tomography (CT) imaging, but did not differ by bystander compressions or use of
      mechanical compression. After multivariable adjustment, only compression time >
      10 min and CT imaging during hospitalization were positively associated with
      detected injury (OR = 7.86 [95% CI = 1.7-35.9] and 6.30 [95% CI = 2.6-15.5],
      respectively). Conclusion. In patients who survived OHCA to admission, longer
      duration of compressions and use of CT during the post-arrest course were
      associated positively with documented compression injury. Compression-induced
      injuries detected via routine post-arrest care are likely to be largely
      insignificant in terms of length of recovery.

PMID- 25076025
TI  - Regulation mechanism and research progress of MeCP2 in Rett syndrome.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disease accountable for
      some of the severe mental retardation of females. Mutations in the gene encoding
      mythyl-CpG-binding protein 2, MeCP2, which acts as a suppressor of gene
      expression, are the primary genetic pathological change of RTT. Insufficient
      binding of MeCP2 with methylated DNA disrupts the proper expression of target
      genes and results in brain dysfunction. Currently, the proper role MeCP2 played
      in the process of brain development and the occurrence of RTT remain elusive. In
      this review, we summarize both the MECP2 gene and MeCP2 protein, with highlight
      upon their structures, functions and more importantly their regulatory mechanisms
      at the molecular level so as to elucidate the mechanisms underlying the
      pathogenesis of RTT. 

PMID- 25076026
TI  - Functions of miR126 and innate immune response.
AB  - MicroRNAs (miRNAs) are endogenous non-coding small RNAs that negatively regulate
      gene expression at the post-transcriptional level by base pairing with target
      mRNAs. Many miRNAs have been proven to regulate a broad range of processes,
      including proliferation, differentiation, development and apoptosis. miR126 is
      encoded by intron 7 of the EGF- like domain 7 (Egfl7) gene and highly expressed
      in human endothelial cells (ECs) and plasmacytoid dendritic cells (pDCs). Based
      on the current knowledge, miR126 is involved in angiogenesis and cancer. Also
      miR126 is the first miRNA which has been reported to involve in preconditioning
      the responsiveness of the host to pathogen infection in the steady state. This
      implicated that miR126 may be the potential therapeutic target for cancer and
      autoimmune diseases. In this review, we summarize the functions of miR126 in
      angiogenesis and cancer, and emphasize its relationship with innate immune
      response. 

PMID- 25076027
TI  - MicroRNAs affect tumor metastasis through regulating epithelial- mesenchymal
      transition.
AB  - Distant metastasis of tumor cell is a series of continuous, selectable cascades
      of events regulated by multiple factors and genes. Epithelial-mesenchymal
      transition (EMT) is a critical step during cancer metastasis. However, the
      mechanism of EMT in tumor is not yet fully elucidated. MicroRNAs (miRNAs) are a
      class of non-coding small endogenous RNAs that negatively regulate EMT-related
      genes at the post-transcriptional level and play critical roles in cancer
      metastasis. This review mainly focuses on the topics that include the
      relationship of EMT and tumor metastasis, transcription factors involved in EMT,
      and the effect of miRNAs on tumor metastasis by targeting the EMT-related
      transcription factors. 

PMID- 25076028
TI  - Advances in miRNA research related to testis development and spermatogenesis.
AB  - MicroRNA (miRNA), a class of non-coding RNA (about 22 nt), widely exists in
      different organisms and plays an important role in regulating cell growth,
      development, and apoptosis. Recently, various studies have demonstrated that
      miRNA also serves as a key mediator during testis development and spermatogenesis
      both in human beings and animals. However, the expression of miRNA in different
      testis from different species showed significant differences. Meanwhile, it also
      showed different expression patterns in different spermatogenesis stages. In this
      review, we summarize different miRNA expression patterns during testis
      development, spermatogenesis, as well as their roles in regulating
      spermatogenesis, which provids insight into the further research on miRNA in
      testis, and ideas for regulating and improving animal sperm quality by using
      miRNA. 

PMID- 25076029
TI  - The regulatory mechanism of microRNAs in skin and hair follicle development.
AB  - MicroRNAs (miRNAs) are an emerging class of regulators that control post
      transcriptional processes, and could be potential targets for drug in pathology
      and potential sites of phenotypic regulation. Although some functions of miRNAs
      have been known, the regulatory mechanism of miRNAs in skin and hair follicle
      development remains unclear. High throughput sequencing provides more accurate
      and rapid method for identification of miRNAs. It has been found that some miRNAs
      affect the cell differentiation and proliferation of skin and hair follicles, and
      their target genes play important roles in the periodic growth of hair follicles.
      In this review, we summarize the recent achievements of the regulatory mechanism
      of miRNAs in the skin follicles and provide useful clues for further study on
      miRNA regulation in hair follicle growth of cashmere goat. 

PMID- 25076030
TI  - Nitric oxide in plants and its role in regulating flower development.
AB  - Nitric oxide (NO) is an essential signaling molecule, which is involved in many
      aspects of plant growth and development. There is increasing evidence that NO
      plays a vital role in the process of flower development, which, however, has not
      been comprehensively reviewed for a long time. In this review, we provide an
      overview of the multiplicity of NO production in plants, and discuss the
      potential repression mechanism of NO in flower transition and the role of NO in
      pollen germination and pollen tube elongation. 

PMID- 25076031
TI  - Advances in phylogenomics.
AB  - Phylogenomics is a new phylogenetic field that aims to rebuild phylogenetic
      relationship of organisms using whole genome data. It can effectively eliminate
      the impact of horizontal gene transfer and variant evolutionary rates on
      phylogeny. According to the genome data type they are based on, these methods can
      be classified into five groups: multi-gene based, gene content based, gene order
      based, K-string based, and metabolic pathway based. The mechanism, speed,
      accuracy, applicable range and their application of these methods are summarized.
      The prospects of phylogenomics and challenges that it is faced with are also
      discussed. 

PMID- 25076032
TI  - Involvement of the CREB5 regulatory network in colorectal cancer metastasis.
AB  - The signal regulatory network involved in colorectal cancer metastasis is
      complicated and thus the search for key control steps in the network is of great
      significance for unraveling colorectal cancer metastasis mechanism and finding
      drug-target site. Previous studies suggested that CREB5 (cAMP responsive element
      binding protein 5) might play key role in the metastatic signal network of
      colorectal cancer. Through colorectal cancer expression profile and enriching
      analysis of the effect of CREB5 gene expression levels on colorectal cancer
      molecular events, we found that these molecular events are correlated with tumor
      metastasis. Based on the feature that CREB5 could combine with c-Jun to form
      heterodimer, together with enriched binding sites for transcription factor AP-1,
      we identified 16 genes which were up-regulated in the CREB5 high-expression
      group, contained AP-1 binding sites, and participated in cancer pathway. The
      molecular network involving these 16 genes, in particular, CSF1R, MMP9, PDGFRB,
      FIGF and IL6, regulates cell migration. Therefore, CREB5 might accelerate the
      metastasis of colorectal cancer by regulating these five key genes. 

PMID- 25076033
TI  - Myostatin knockout in bovine fetal fibroblasts by using TALEN.
AB  - Myostatin (MSTN) can negatively regulate the growth and development of skeletal
      muscle, and mutations of bovine MSTN gene can cause a "double-muscle" feature. To
      knock out MSTN gene in bovine fetal fibroblast by transcription activator-like
      effector nucleases (TALENs) and obtain MSTN knockout cell lines, we constructed
      one pair of MSTN-TALEN vector and transfected into bovine fetal fibroblast cells
      by PEI and electroporation. Sequencing results demonstrated that TALEN was
      available for MSTN knockout. T7 endonuclease 1 (T7E1) was used for the detection
      of mutation efficiency. The results indicated that knockout efficiency of
      electroporation transfection was 20.4%, and 10 MSTN(+/-) and MSTN(-/-) cell
      colonies were obtained via limiting dilution method. The deletion number of
      nucleotides ranged from 1 to 20, and some of them were frameshift mutation, which
      could provide the possibility in production of MSTN knockout cattle in the
      future. 

PMID- 25076034
TI  - Direct sequencing of DNA pooling for screening highly informative SNPs in dairy
      cattle.
AB  - In this study, 139 bovine single nuclear polymorphisms (SNPs) were firstly
      selected and then directly sequenced using DNA pooling. Based on the ratio of two
      signal peak values, 92 SNPs with the ratio over 1/2 were considered as potential
      highly informative markers. To further verify the reliability of screening
      system, 59 SNP markers were genotyped in 122 Holstein cattle using matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF
      MS) method. The results showed that 56 SNPs had a call rate higher than 85%. The
      minor allele frequency (MAF) of these 56 markers ranged from 0.27 to 0.5, with an
      average of 0.41; and in which 54 markers had a MAF over 0.3, covering 96.4% of
      this group of markers (54/56). Our findings indicate that direct sequencing of
      DNA pooling is a useful and efficient tool for identifying highly informative
      SNPs. 

PMID- 25076035
TI  - Response of maize serine/arginine-rich protein gene family in seedlings to
      drought stress.
AB  - Alternative splicing (AS) in eukaryotic organisms is closely related to the gene
      regulation in plant abiotic stress responses, in which serine/arginine-rich
      proteins (SR proteins) act as key regulators. The genome sequence of maize inbred
      line B73 was analyzed, showing that the promoter regions of SR genes possess
      about three to eight kinds of cis-acting regulatory elements. Twenty-seven SR
      genes encode alkaline proteins, and 23 of which are divided into five subgroups
      in terms of the first RNA recognition motif (RRM) at the amino terminal. The
      expression of SR genes showed tissue-specific and genotype-dependent features
      under drought stress in the hybrid Zhengdan-958 and its parents, Zheng-58 and
      Chang-7-2 via bidirectional hierarchical clustering. SR genes were down-regulated
      in roots while they were up-regulated in shoots under drought stress. However, SR
      genes were down-regulated in both roots and shoots in three different rehydration
      stages after severe drought stress. Additionally, a widespread alternative
      splicing exists in all SR genes although SR genes showed differential expression
      tendency under drought stress and/or during rehydration stages. Results above
      will deepen our understanding of the molecular mechanisms of plant response to
      abiotic stress from the perspective of AS-network. 

PMID- 25076036
TI  - Function of chalcone reductase gene CHR1 in soybean.
AB  - To verify the function of chalcone reductase gene (CHR1) in soybean Daidzein
      synthesis, CHR1 gene in soybean was cloned, and an RNAi expression vector pCPB
      CHR1-RNAi was constructed. Four transformed plants in T0 generation and thirteen
      transformed plants in T1 generation of soybean "Jinong28" were obtained by
      agrobacterium-mediated genetic transformation, in which transcriptions of CHR1
      gene were depressed. Southern blotting showed the functional fragment of pCPB
      CHR1-RNAi was integrated into the genome of recipient soybean in the form of a
      single copy. Detection of the transcription of CHR1 gene using quantitative real
      time PCR (qRT-PCR) showed that the expression of CHR1 gene in transformed plants
      decreased 60%-99% compared to the recipient soybean, while the content of
      isoliquiritigenin, the precursors of daidzein, decreased 38.7%. These results
      indicate that RNA interference can suppress the transcription of CHR1 gene
      expression successfully. 

PMID- 25076037
TI  - Sequence variation of P1 gene in Potato virus Y isolated from Fujian Province.
AB  - To understand the sequence variation and the putative protein structure of P1
      gene in Potato virus Y (PVY) and to identify the sources of the variation, P1
      gene in PVY isolated from Fujian Province was amplified by reverse-transcription
      polymerase chain reaction (RT-PCR) using a pair of degenerate primers designed
      from the conserved regions of published sequences. Sequence variation and
      putative protein structure were analyzed, and phylogenetic tree was reconstructed
      using Bayesian inference method. Expected fragments of 915 bp in size were
      amplified from 12 samples collected from Fujian Province by RT-PCR. The 12
      sequences shared 73%-99% nucleotide identity with the reference sequences from
      GenBank. A strong recombination signal was identified at position 309 in
      sequences of isolates QK44, XT02, XT08 and LH05. Among the 12 sequences, 85 amino
      acid variants were detected, indicating high sequence variation in the P1
      protein. However, positions 41-275 in the protein were highly conserved,
      especially in three active sites (H192, D201 and V235). Phylogenetic analysis
      grouped the sequences into three clades, each with different Coiled-coil domains
      and 3D-structures, suggesting divergent phylogenetic relationship among the
      groups. The above results show P1 gene in PVY is highly variable but contains 3
      conserved active sites (H192, D201, V235) and the high genetic variation in the
      gene is primarily due to mutation and recombination.

PMID- 25076038
TI  - Large scale screening of genetic interaction with sgf73(+) in fission yeast.
AB  - Genetic interaction (GI) not only suggests functional correlations between
      different genes in vivo, but also provides clues for understanding the potential
      biological function of a specific gene. Screening of GI is an important method
      for understanding GI between different genes. In this study, we selected sgf73+
      as a query, which encodes a subunit of SAGA (Spt-Ada-Gcn5 acetyltransferase)
      complex deubiquitination module, to perform a large scale screening of GI in
      fission yeast. Our data showed that 164 genes had negative GIs whereas 42 genes
      had positive GIs with sgf73+. GO (Gene ontology) analysis indicated that these
      genes were enriched in several important biological processes, including
      chromatin modification, DNA damage repair, cellular response to stress, RNA
      transcription and so on. By using histone modification detection, we showed for
      the first time that loss of sgf73+ led to a decreased level of histone
      acetylation at H3K9 and H4K16 and an increased level of histone H3K4 methylation.
      Furthermore, the spot assay results showed that the sgf73? cells exhibited
      increased sensitivity to DNA damage agents, HU and CPT, and sgf73+ was involved
      in responses to hyperoxia stress. All these results suggested that sgf73+ plays
      important roles in chromatin modification, DNA damage repair and hyperoxia
      responses.

PMID- 25076039
TI  - An exploration for research-oriented teaching model in biology teaching.
AB  - Training innovative talents, as one of the major aims for Chinese universities,
      needs to reform the traditional teaching methods. The research-oriented teaching
      method has been introduced and its connotation and significance for Chinese
      university teaching have been discussed for years. However, few practical
      teaching methods for routine class teaching were proposed. In this paper, a
      comprehensive and concrete research-oriented teaching model with contents of
      reference value and evaluation method for class teaching was proposed based on
      the current teacher-guiding teaching model in China. We proposed that the
      research-oriented teaching model should include at least seven aspects on: (1)
      telling the scientific history for the skills to find out scientific questions;
      (2) replaying the experiments for the skills to solve scientific problems; (3)
      analyzing experimental data for learning how to draw a conclusion; (4) designing
      virtual experiments for learning how to construct a proposal; (5) teaching the
      lesson as the detectives solve the crime for learning the logic in scientific
      exploration; (6) guiding students how to read and consult the relative
      references; (7) teaching students differently according to their aptitude and
      learning ability. In addition, we also discussed how to evaluate the effects of
      the research-oriented teaching model in examination. 

PMID- 25076040
TI  - Outbreaks caused by sprouts, United States, 1998-2010: lessons learned and
      solutions needed.
AB  - After a series of outbreaks associated with sprouts in the mid-1990s, the U.S.
      Food and Drug Administration (FDA) published guidelines in 1999 for sprouts
      producers to reduce the risk of contamination. The recommendations included
      treating seeds with an antimicrobial agent such as calcium hypochlorite solution
      and testing spent irrigation water for pathogens. From 1998 through 2010, 33
      outbreaks from seed and bean sprouts were documented in the United States,
      affecting 1330 reported persons. Twenty-eight outbreaks were caused by
      Salmonella, four by Shiga toxin-producing Escherichia coli, and one by Listeria.
      In 15 of the 18 outbreaks with information available, growers had not followed
      key FDA guidelines. In three outbreaks, however, the implicated sprouts were
      produced by firms that appeared to have implemented key FDA guidelines. Although
      seed chlorination, if consistently applied, reduces pathogen burden on sprouts,
      it does not eliminate the risk of human infection. Further seed and sprouts
      disinfection technologies, some recently developed, will be needed to enhance
      sprouts safety and reduce human disease. Improved seed production practices could
      also decrease pathogen burden but, because seeds are a globally distributed
      commodity, will require international cooperation.

PMID- 25076041
TI  - Relationship of self-rated health with fatal and non-fatal outcomes in
      cardiovascular disease: a systematic review and meta-analysis.
AB  - BACKGROUND: People who rate their health as poor experience higher all-cause
      mortality. Study of disease-specific association with self-rated health might
      increase understanding of why this association exists. OBJECTIVES: To estimate
      the strength of association between self-rated health and fatal and non-fatal
      cardiovascular disease. METHODS: A comprehensive search of PubMed MEDLINE,
      EMBASE, CINAHL, BIOSIS, PsycINFO, DARE, Cochrane Library, and Web of Science was
      undertaken during June 2013. Two reviewers independently searched databases and
      selected studies. Inclusion criteria were prospective cohort studies or cohort
      analyses of randomised trials with baseline measurement of self-rated health with
      fatal or non-fatal cardiovascular outcomes. 20 studies were pooled quantitatively
      in different meta-analyses. Study quality was assessed using Newcastle-Ottawa
      scales. RESULTS: 'Poor' relative to 'excellent' self-rated health (defined by
      most extreme categories in each study, most often' poor' or 'very poor' and
      'excellent' or 'good') was associated over a follow-up of 2.3-23 years with
      cardiovascular mortality in studies: where varying degrees of adjustments had
      been made for cardiovascular disease risk (HR 1.79 (95% CI 1.50 to 2.14); 15
      studies, I2 = 71.24%), and in studies reporting outcomes in people with pre
      existing cardiovascular disease or ischaemic heart disease symptoms (HR 2.42 (95%
      CI 1.32 to 4.44); 3 studies; I2 = 71.83%). 'Poor' relative to 'excellent' self
      rated health was also associated with the combined outcome of fatal and non-fatal
      cardiovascular events (HR 1.90 (95% CI 1.26 to 2.87); 5 studies; I2 = 68.61%),
      Self-rated health was not significantly associated with non-fatal cardiovascular
      disease outcomes (HR 1.66 (95% CI 0.96 to 2.87); 5 studies; I2 = 83.60%).
      CONCLUSIONS: Poor self rated health is associated with cardiovascular mortality
      in populations with and without prior cardiovascular disease. Those with current
      poor self-rated health may warrant additional input from health services to
      identify and address reasons for their low subjective health.

PMID- 25076042
TI  - Longer and less overlapping food webs in anthropogenically disturbed marine
      ecosystems: confirmations from the past.
AB  - The human exploitation of marine resources is characterised by the preferential
      removal of the largest species. Although this is expected to modify the structure
      of food webs, we have a relatively poor understanding of the potential
      consequences of such alteration. Here, we take advantage of a collection of
      ancient consumer tissues, using stable isotope analysis and SIBER to assess
      changes in the structure of coastal marine food webs in the South-western
      Atlantic through the second half of the Holocene as a result of the sequential
      exploitation of marine resources by hunter-gatherers, western sealers and modern
      fishermen. Samples were collected from shell middens and museums. Shells of both
      modern and archaeological intertidal herbivorous molluscs were used to
      reconstruct changes in the stable isotopic baseline, while modern and
      archaeological bones of the South American sea lion Otaria flavescens, South
      American fur seal Arctocephalus australis and Magellanic penguin Spheniscus
      magellanicus were used to analyse changes in the structure of the community of
      top predators. We found that ancient food webs were shorter, more redundant and
      more overlapping than current ones, both in northern-central Patagonia and
      southern Patagonia. These surprising results may be best explained by the huge
      impact of western sealing on pinnipeds during the fur trade period, rather than
      the impact of fishing on fish populations. As a consequence, the populations of
      pinnipeds at the end of the sealing period were likely well below the ecosystem's
      carrying capacity, which resulted in a release of intraspecific competition and a
      shift towards larger and higher trophic level prey. This in turn led to longer
      and less overlapping food webs.

PMID- 25076043
TI  - Ligand-receptor affinities computed by an adapted linear interaction model for
      continuum electrostatics and by protein conformational averaging.
AB  - Accurate calculations of free energies involved in small-molecule binding to a
      receptor are challenging. Interactions between ligand, receptor, and solvent
      molecules have to be described precisely, and a large number of conformational
      microstates has to be sampled, particularly for ligand binding to a flexible
      protein. Linear interaction energy models are computationally efficient methods
      that have found considerable success in the prediction of binding free energies.
      Here, we parametrize a linear interaction model for implicit solvation with
      coefficients adapted by ligand and binding site relative polarities in order to
      predict ligand binding free energies. Results obtained for a diverse series of
      ligands suggest that the model has good predictive power and transferability. We
      also apply implicit ligand theory and propose approximations to average
      contributions of multiple ligand-receptor poses built from a protein
      conformational ensemble and find that exponential averages require proper energy
      discrimination between plausible binding poses and false-positives (i.e.,
      decoys). The linear interaction model and the averaging procedures presented can
      be applied independently of each other and of the method used to obtain the
      receptor structural representation. 

PMID- 25076045
TI  - Optical properties of diatom nanostructured biosilica in Arachnoidiscus sp: micro
      optics from mother nature.
AB  - Some natural structures show three-dimensional morphologies on the micro- and
      nano-scale, characterized by levels of symmetry and complexity well far beyond
      those fabricated by best technologies available. This is the case of diatoms,
      unicellular microalgae, whose protoplasm is enclosed in a nanoporous microshell,
      made of hydrogenated amorphous silica, called frustule. We have studied the
      optical properties of Arachnoidiscus sp. single valves both in visible and
      ultraviolet range. We found photonic effects due to diffraction by ordered
      pattern of pores and slits, accordingly to an elaborated theoretical model. For
      the first time, we experimentally revealed spatial separation of focused light in
      different spots, which could be the basis of a micro-bio-spectrometer.
      Characterization of such intricate structures can be of great inspiration for
      photonic devices of next generation.

PMID- 25076046
TI  - Synthesis of novel ZnV2O4 hierarchical nanospheres and their applications as
      electrochemical supercapacitor and hydrogen storage material.
AB  - Hierarchical nanostructures (Hs) have recently garnered enormous attention due to
      their remarkable performances in catalysis, electronic devices, energy storage
      and conversion. Considering the advantage of hierarchical nanostructures, we have
      formulated a facile and template free method to synthesize novel hierarchical
      nanospheres (NHNs) of ZnV2O4. Both zinc and vanadium are earth abundant,
      relatively economical and can offer several oxidation states, which can render a
      broad range of redox reactions favorable for electrochemical energy storage
      applications. Keeping these points in mind, we investigated for the first time
      the electrochemical supercapacitor performance of NHNs. The electrochemical
      measurements were performed in 2 M KOH solution. The measured specific
      capacitance of ZnV2O4 electrode is 360 F/g at 1 A/g with good stability and
      retention capacity of 89% after 1000 cycles. Moreover, the hydrogen storage
      properties of NHNs were measured at 473, 573, and 623 K with an absorption of
      1.76, 2.03, and 2.49 wt %. respectively. These studies pave the way to consider
      ZnV2O4 as prospective material for energy storage applications. 

PMID- 25076044
TI  - The quality of methods reporting in parasitology experiments.
AB  - There is a growing concern both inside and outside the scientific community over
      the lack of reproducibility of experiments. The depth and detail of reported
      methods are critical to the reproducibility of findings, but also for making it
      possible to compare and integrate data from different studies. In this study, we
      evaluated in detail the methods reporting in a comprehensive set of
      trypanosomiasis experiments that should enable valid reproduction, integration
      and comparison of research findings. We evaluated a subset of other parasitic
      (Leishmania, Toxoplasma, Plasmodium, Trichuris and Schistosoma) and non-parasitic
      (Mycobacterium) experimental infections in order to compare the quality of method
      reporting more generally. A systematic review using PubMed (2000-2012) of all
      publications describing gene expression in cells and animals infected with
      Trypanosoma spp was undertaken based on PRISMA guidelines; 23 papers were
      identified and included. We defined a checklist of essential parameters that
      should be reported and have scored the number of those parameters that are
      reported for each publication. Bibliometric parameters (impact factor, citations
      and h-index) were used to look for association between Journal and Author status
      and the quality of method reporting. Trichuriasis experiments achieved the
      highest scores and included the only paper to score 100% in all criteria. The
      mean of scores achieved by Trypanosoma articles through the checklist was 65.5%
      (range 32-90%). Bibliometric parameters were not correlated with the quality of
      method reporting (Spearman's rank correlation coefficient <-0.5; p>0.05). Our
      results indicate that the quality of methods reporting in experimental
      parasitology is a cause for concern and it has not improved over time, despite
      there being evidence that most of the assessed parameters do influence the
      results. We propose that our set of parameters be used as guidelines to improve
      the quality of the reporting of experimental infection models as a pre-requisite
      for integrating and comparing sets of data. 

PMID- 25076047
TI  - Base-mediated intramolecular C- and N-arylation of N,N-disubstituted 2
      nitrobenzenesulfonamides: advanced intermediates for the synthesis of diverse
      nitrogenous heterocycles.
AB  - Structural and electronic features that facilitate and direct the intramolecular
      C- and N-arylation of 2-alkyl-2-{[N-(benzyl)-2-nitrophenyl]sulfonamido}acetic
      acid esters and amides were examined. The substitution pattern and amino acid
      carboxy-terminal functionality determined the arylation position. C/N-arylated
      products represent advanced intermediates for combinatorial synthesis of diverse
      nitrogenous heterocycles, including indazoles, quinazolinones, quinoxalinones,
      and 3-amino-2-oxindoles. 

PMID- 25076049
TI  - Systematic tuning of heme redox potentials and its effects on O2 reduction rates
      in a designed oxidase in myoglobin.
AB  - Cytochrome c Oxidase (CcO) is known to catalyze the reduction of O2 to H2O
      efficiently with a much lower overpotential than most other O2 reduction
      catalysts. However, methods by which the enzyme fine-tunes the reduction
      potential (E degrees ) of its active site and the corresponding influence on the
      O2 reduction activity are not well understood. In this work, we report systematic
      tuning of the heme E degrees  in a functional model of CcO in myoglobin
      containing three histidines and one tyrosine in the distal pocket of heme. By
      removing hydrogen-bonding interactions between Ser92 and the proximal His ligand
      and a heme propionate, and increasing hydrophobicity of the heme pocket through
      Ser92Ala mutation, we have increased the heme E degrees  from 95 +/- 2 to 123 +/-
      3 mV. Additionally, replacing the native heme b in the CcO mimic with heme a
      analogs, diacetyl, monoformyl, and diformyl hemes, that posses electron
      withdrawing groups, resulted in higher E degrees  values of 175 +/- 5, 210 +/- 6,
      and 320 +/- 10 mV, respectively. Furthermore, O2 consumption studies on these CcO
      mimics revealed a strong enhancement in O2 reduction rates with increasing heme E
      degrees . Such methods of tuning the heme E degrees  through a combination of
      secondary sphere mutations and heme substitutions can be applied to tune E
      degrees  of other heme proteins, allowing for comprehensive investigations of the
      relationship between E degrees  and enzymatic activity. 

PMID- 25076051
TI  - Divergent chemo-, regio-, and diastereoselective normal electron-demand Povarov
      type reactions with alpha-oxo-ketene dienophiles.
AB  - The reactions between electron-rich 2-aza-dienes and alpha-oxo-ketenes derived
      from the Wolff rearrangement of 2-diazocycloalkane-1,3-diones chemo- and
      regioselectively produced spiro hydropyrid-4-ones with good to excellent
      diastereoselectivities. These reactions are likely to proceed via a domino
      Wolff/Friedel-Crafts/intramolecular Mannich process. Prolonged domino sequences
      also allowed the expeditious preparation of a series of pyrazolopyridine and
      pyridopyrimidine heterocycles. 

PMID- 25076050
TI  - Severe morbidity according to sex in the era of combined antiretroviral therapy:
      the ANRS CO3 Aquitaine Cohort.
AB  - OBJECTIVE: To describe trends and determinants of severe morbidity in HIV
      infected women and men. DESIGN: A French prospective cohort of HIV-infected
      patients of both sexes and all transmission categories. METHODS: We used hospital
      admission data from January 2000 to December 2008. A severe morbid event (SME)
      was defined as a clinical event requiring hospitalization for >=48 h, several
      events could be reported during hospitalization. Yearly incidence rates of SME
      were estimated and compared using Generalized Estimating Equations. RESULTS:
      Among 4,987 patients (27% women), followed for a median of 8.7 years, 1,473 (30%)
      were hospitalized (3,049 hospitalizations for 5,963 SME). The yearly incidence
      rate of hospitalization decreased in men, from 155 in 2000 to 80/1,000 person
      years (PY) in 2008 and in women, from 125 to 71/1,000 PY, (p<0.001). This trend
      was observed for all SME except for hepatic events, stable in men (15 to 13/1,000
      PY) and increasing in women (2.5 to 11.5), cardiovascular events increasing in
      men (6 to 10/1,000 PY) and in women (6 to 14) and non-AIDS non-hepatic
      malignancies increasing in men (4 to 7/1,000 PY) and stable in women (2.5).
      Intraveneous drug users, age >50 years, HIV RNA >10,000 copies, CD4 <500/mm3,
      AIDS stage, hepatitis C co-infection and cardiovascular risk factors (diabetes,
      high blood pressure, and tobacco use) were associated with SME. CONCLUSIONS: HIV
      infected individuals in care in France require less and less frequently
      hospitalization. Women are now presenting with severe hepatic and cardio-vascular
      events. Disparities in SME between men and women are primarily explained by
      different exposure patterns to risk factors. Women should be targeted to benefit
      cardiovascular prevention policies as well as men.

PMID- 25076052
TI  - Microhabitat types promote the genetic structure of a micro-endemic and
      critically endangered mole salamander (Ambystoma leorae) of Central Mexico.
AB  - The reduced immigration and emigration rates resulting from the lack of landscape
      connectivity of patches and the hospitality of the intervening matrix could favor
      the loss of alleles through genetic drift and an increased chance of inbreeding.
      In order for isolated populations to maintain sufficient levels of genetic
      diversity and adapt to environmental changes, one important conservation goal
      must be to preserve or reestablish connectivity among patches in a fragmented
      landscape. We studied the last known population of Ambystoma leorae, an endemic
      and critically threatened species. The aims of this study were: (1) to assess the
      demographic parameters of A. leorae and to distinguish and characterize the
      microhabitats in the river, (2) to determine the number of existing genetic
      groups or demes of A. leorae and to describe possible relationships between
      microhabitats types and demes, (3) to determine gene flow between demes, and (4)
      to search for geographic locations of genetic discontinuities that limit gene
      flow between demes. We found three types of microhabitats and three genetically
      differentiated subpopulations with a significant level of genetic structure. In
      addition, we found slight genetic barriers. Our results suggest that mole
      salamander's species are very sensitive to microhabitat features and relatively
      narrow obstacles in their path. The estimates of bidirectional gene flow are
      consistent with the pattern of a stepping stone model between demes, where
      migration occurs between adjacent demes, but there is low gene flow between
      distant demes. We can also conclude that there is a positive correlation between
      microhabitats and genetic structure in this population. 

PMID- 25076053
TI  - Migration, foraging, and residency patterns for Northern Gulf loggerheads:
      implications of local threats and international movements.
AB  - Northern Gulf of Mexico (NGoM) loggerheads (Caretta caretta) make up one of the
      smallest subpopulations of this threatened species and have declining nest
      numbers. We used satellite telemetry and a switching state-space model to
      identify distinct foraging areas used by 59 NGoM loggerheads tagged during 2010
      2013. We tagged turtles after nesting at three sites, 1 in Alabama (Gulf Shores;
      n = 37) and 2 in Florida (St. Joseph Peninsula; n = 20 and Eglin Air Force Base;
      n = 2). Peak migration time was 22 July to 9 August during which >40% of turtles
      were in migration mode; the mean post-nesting migration period was 23.0 d (+/
      13.8 d SD). After displacement from nesting beaches, 44 turtles traveled to
      foraging sites where they remained resident throughout tracking durations.
      Selected foraging locations were variable distances from tagging sites, and in 5
      geographic regions; no turtles selected foraging sites outside the Gulf of Mexico
      (GoM). Foraging sites delineated using 50% kernel density estimation were located
      a mean distance of 47.6 km from land and in water with mean depth of -32.5 m;
      other foraging sites, delineated using minimum convex polygons, were located a
      mean distance of 43.0 km from land and in water with a mean depth of -24.9 m.
      Foraging sites overlapped with known trawling activities, oil and gas extraction
      activities, and the footprint of surface oiling during the 2010 Deepwater Horizon
      oil spill (n = 10). Our results highlight the year-round use of habitats in the
      GoM by loggerheads that nest in the NGoM. Our findings indicate that protection
      of females in this subpopulation requires both international collaborations and
      management of threats that spatially overlap with distinct foraging habitats. 

PMID- 25076054
TI  - Dynamics of chlorine atom reactions with hydrocarbons: insights from imaging the
      radical product in crossed beams.
AB  - We present a comprehensive overview of our ongoing studies applying dc slice
      imaging in crossed molecular beams to probe the dynamics of chlorine atom
      reactions with polyatomic hydrocarbons. Our approach consists in measuring the
      full velocity-flux contour maps of the radical products using vacuum ultraviolet
      "soft" photoionization at 157 nm. Our overall goal is to extend the range of
      chemical dynamics investigations from simple triatomic or tetraatomic molecules
      to systematic investigations of a sequence of isomers or a homologous series of
      reactants of intermediate size. These experimental investigations are augmented
      by high-level ab initio calculations which, taken together, reveal trends in
      product energy and angular momentum partitioning and offer deep insight into the
      reaction mechanisms as a function of structure, bonding patterns, and kinematics.
      We explore these issues in alkanes, for which only direct reactive encounters are
      found, and in unsaturated hydrocarbons, for which an addition-elimination
      mechanism competes with direct abstraction. The results for alkene addition
      elimination in particular suggest a new view of these reactions: The only pathway
      to HCl elimination is accessed by means of roaming excursions of the Cl atom from
      the strongly bound adduct. 

PMID- 25076055
TI  - Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and
      metabolism in adult female offspring.
AB  - Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control
      malaria, typhus, body lice and bubonic plague worldwide, until countries began
      restricting its use in the 1970s. Its use in malaria control continues in some
      countries according to recommendation by the World Health Organization.
      Individuals exposed to elevated levels of DDT and its metabolite
      dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes
      and insulin resistance. Here we hypothesize that perinatal exposure to DDT
      disrupts metabolic programming leading to impaired metabolism in adult offspring.
      To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to
      postnatal day 5 and studied their metabolic phenotype at several ages up to nine
      months. Perinatal DDT exposure reduced core body temperature, impaired cold
      tolerance, decreased energy expenditure, and produced a transient early-life
      increase in body fat in female offspring. When challenged with a high fat diet
      for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed
      glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid
      metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood
      further impaired thermogenesis as evidenced by reductions in core temperature and
      in the expression of numerous RNA that promote thermogenesis and substrate
      utilization in the brown adipose tissue of adult female mice. These observations
      suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of
      carbohydrates and lipids which may increase susceptibility to the metabolic
      syndrome in adult female offspring. 

PMID- 25076057
TI  - Computational design of two-photon fluorescent probes for intracellular free zinc
      ions.
AB  - Two-photon fluorescence probes used in two-photon fluorescence microscopy (TPM)
      can achieve intact tissue imaging without destruction. Therefore, for a long
      time, TPM has been an important tool in biology and medicine. In this background
      via a quantum chemical method, a series of zinc ion probe molecules using N,N
      di(2-picolyl)ethylenediamine (DPEN) as the recognition group were studied, which
      are based on the photoinduced electron transfer (PET) mechanism. The fact that
      the one-photon absorption peak is almost unchanged and the fluorescence emission
      intensity increased significantly upon coordination with a zinc ion reveals that
      these probes can be PET fluorescent bioimaging reagents. And it is predicted that
      when the chemically modified probe molecule is incorporated with Zn(2+), the two
      photon absorption (TPA) cross-section (deltamax) will greatly increase and the
      TPA peak will be in the near-infrared region. The molecules after changing the
      fluorophore become more suitable for probing Zn(2+) in vivo, and a modification
      at the end of the fluorophore can fine-tune the fluorescence and TPA properties.
      The detailed investigations will provide a theoretical basis for synthesizing new
      zinc-ion-responsive two-photon fluorescent probes. 

PMID- 25076056
TI  - Gastrointestinal nematodes and anthelmintic resistance in Danish goat herds.
AB  - The prevalence of gastrointestinal parasites in Danish goats and the presence of
      anthelmintic resistance (AR) in 10 selected herds were investigated during April
      September 2012. All Danish herds (n = 137) with 10 or more adult goats were
      invited to participate, and of these 27 herds met the inclusion criterion of more
      than 10 young kids never treated with anthelmintics. Questionnaire data on
      management were collected, and faecal samples from 252 kids were analysed by the
      McMaster technique. From all herds with a mean faecal egg count (FEC) above 300
      eggs per g of faeces, pooled samples were stained with peanut agglutinin (PNA)
      for specific detection of Haemonchus contortus. Strongyle eggs were detected with
      an individual prevalence of 69%, including Nematodirus battus (3.6%) and other
      Nematodirus species (15.0%). Eimeria spp. were observed in 99.6% of the kids. H.
      contortus was found in 11 of 12 (92%) tested herds. Anthelmintics were used in
      89% of the herds with mean treatment frequencies of 0.96 and 0.89 treatments per
      year for kids and adults, respectively. In 2011, new animals were introduced into
      44% of the herds of which 25% practised quarantine anthelmintic treatments. In 10
      herds the presence of AR was analysed by egg hatch assay and FEC reduction tests
      using ivermectin (0.3 mg/kg) or fenbendazole (10.0 mg/kg). AR against both
      fenbendazole and ivermectin was detected in seven herds; AR against fenbendazole
      in one herd, and AR against ivermectin in another herd. In conclusion, resistance
      to the most commonly used anthelmintics is widespread in larger goat herds
      throughout Denmark. 

PMID- 25076058
TI  - Development of Pd-Cu/hematite catalyst for selective nitrate reduction.
AB  - A new hematite-supported Pd-Cu bimetallic catalyst (Pd-Cu/hematite) was developed
      in order to actively and selectively reduce nitrate (NO3(-)) to nitrogen gas
      (N2). Four different iron-bearing soil minerals (hematite (H), goethite (G),
      maghemite (M), and lepidocrocite (L)) were transformed to hematite by calcination
      and used for synthesis of different Pd-Cu/hematite-H, G, M, and L catalysts.
      Their characteristics were identified using X-ray diffraction (XRD), specific
      surface area (BET), temperature programed reduction (TPR), transmission electron
      microscopy with energy dispersive X-ray (TEM-EDX), H2 pulse chemisorption, zeta
      potential, and X-ray photoelectron spectroscopy (XPS). Pd-Cu/hematite-H exhibited
      the highest NO3(-) removal (96.4%) after 90 min, while a lower removal (90.9,
      51.1, and 30.5%) was observed in Pd-Cu/hematite-G, M, and L, respectively. The
      results of TEM-EDX, and TPR analysis revealed that Pd-Cu/hematite-H possessed the
      closest contact distance between the Cu and Pd sites on the hematite surface
      among the different Pd-Cu/hematite catalysts. The high removal can be also
      attributed to the highly active metallic sites on its positively charged surface.
      The XPS analysis demonstrated that the amount of hydrogen molecules can have a
      pivotal function on NO3(-) removal and a ratio of nitrogen to hydrogen molecule
      (N:H) on the Pd sites can critically determine N2 selectivity. 

PMID- 25076059
TI  - Ganoboninketals A-C, Antiplasmodial 3,4-seco-27-Norlanostane Triterpenes from
      Ganoderma boninense Pat.
AB  - Three new nortriterpenes, ganoboninketals A-C (1-3), featuring rearranged 3,4
      seco-27-norlanostane skeletons and highly complex polycyclic systems were
      isolated from the medicinal mushroom Ganoderma boninense. The structures of the
      new metabolites were established by spectroscopic methods. The absolute
      configurations in 1-3 were assigned by electronic circular dichroism (ECD)
      calculations. Compounds 1-3 showed antiplasmodial activity against Plasmodium
      falciparum with IC50 values of 4.0, 7.9, and 1.7 MUM, respectively. Compounds 1
      and 3 also displayed weak cytotoxicity against A549 cell line with IC50 values of
      47.6 and 35.8 MUM, respectively. Compound 2 showed weak cytotoxicity toward HeLa
      cell line with an IC50 value of 65.5 MUM. Compounds 1-3 also presented NO
      inhibitory activity in the LPS-induced macrophages with IC50 values of 98.3,
      24.3, and 60.9 MUM, respectively. 

PMID- 25076060
TI  - Marinopyrrole derivatives with sulfide spacers as selective disruptors of Mcl-1
      binding to pro-apoptotic protein Bim.
AB  - A series of novel marinopyrroles with sulfide and sulphone spacers were designed
      and synthesized. Their activity to disrupt the binding of the pro-apoptotic
      protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using
      ELISA assays. Fluorescence-quenching (FQ) assays confirmed the direct binding of
      marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide
      derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors
      (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide
      derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over
      Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally
      potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl
      xL/Bim binding. Some of the derivatives were also active in intact human breast
      cancer cells where they reduced the levels of Mcl-1, induced programd cell death
      (apoptosis) and inhibited cell proliferation. 

PMID- 25076062
TI  - New antioxidative secondary metabolites from the fruits of a Beibu Gulf mangrove,
      Avicennia marina.
AB  - Further chemical investigation of the fruits of the mangrove, Avicennia marina,
      afforded three new phenylethyl glycosides, marinoids J-L (1-3), and a new
      cinnamoyl glycoside, marinoid M (4). The structures of isolates were elucidated
      on the basis of extensive spectroscopic analysis and by comparison of the data
      with those of related secondary metabolites. The antioxidant activity of the
      isolates was evaluated using the cellular antioxidant assay (CAA), and compounds
      1-4 showed antioxidant activities, with EC50 values ranging from 23.0 +/- 0.71
      MUM to 247.8 +/- 2.47 MUM. 

PMID- 25076061
TI  - Activation of dormant secondary metabolite production by introducing neomycin
      resistance into the deep-sea fungus, Aspergillus versicolor ZBY-3.
AB  - A new ultrasound-mediated approach has been developed to introduce neomycin
      resistance to activate silent pathways for secondary metabolite production in a
      bio-inactive, deep-sea fungus, Aspergillus versicolor ZBY-3. Upon treatment of
      the ZBY-3 spores with a high concentration of neomycin by proper ultrasound
      irradiation, a total of 30 mutants were obtained by single colony isolation. The
      acquired resistance of the mutants to neomycin was confirmed by a resistance
      test. In contrast to the ZBY-3 strain, the EtOAc extracts of 22 of the 30 mutants
      inhibited the human cancer K562 cells, indicating that these mutants acquired a
      capability to produce antitumor metabolites. HPLC-photodiode array detector
      (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses of the EtOAc
      extracts of seven bioactive mutants and the ZBY-3 strain indicated that diverse
      secondary metabolites have been newly produced in the mutant extracts in contrast
      to the ZBY-3 extract. The followed isolation and characterization demonstrated
      that six metabolites, cyclo(D-Pro-D-Phe) (1), cyclo(D-Tyr-D-Pro) (2), phenethyl 5
      oxo-L-prolinate (3), cyclo(L-Ile-L-Pro) (4), cyclo(L-Leu-L-Pro) (5) and
      3beta,5alpha,9alpha-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (6), were newly
      produced by the mutant u2n2h3-3 compared to the parent ZBY-3 strain. Compound 3
      was a new compound; 2 was isolated from a natural source for the first time, and
      all of these compounds were also not yet found in the metabolites of other A.
      versicolor strains. Compounds 1-6 inhibited the K562 cells, with inhibition rates
      of 54.6% (1), 72.9% (2), 23.5% (3), 29.6% (4), 30.9% (5) and 51.1% (6) at 100
      MUg/mL, and inhibited also other human cancer HL-60, BGC-823 and HeLa cells, to
      some extent. The present study demonstrated the effectiveness of the ultrasound
      mediated approach to activate silent metabolite production in fungi by
      introducing acquired resistance to aminoglycosides and its potential for
      discovering new compounds from silent fungal metabolic pathways. This approach
      could be applied to elicit the metabolic potentials of other fungal isolates to
      discover new compounds from cryptic secondary metabolites.

PMID- 25076063
TI  - Entecavir as a first-line treatment for hepatitis B virus reactivation following
      polychemotherapy for chronic lymphocytic leukemia and invasive ductal carcinoma:
      a report of two cases and review of the literature.
AB  - OBJECTIVE: Hepatitis B reactivation has been reported in chronic carriers of
      hepatitis B [hepatitis B surface antigen (HBsAg)] or in patients with prior
      hepatitis B virus (HBV) infection who are HBsAg-negative and have antibodies
      against hepatitis B core antigen (anti-HBc) with or without antibodies to HBsAg
      (anti-HBs). Lamivudine has been the first and commonly used nucleoside analog to
      inhibit HBV replication; however, prolonged therapy has been associated with an
      increased risk for drug-resistant mutations and mortality rates. Entecavir, a
      deoxyguanosine analog, offers several advantages over lamivudine for the
      treatment of HBV reactivation following chemotherapy while exhibiting more potent
      antiviral activity and a lower resistance rate. METHODS: Herein, we report rapid
      and sustained suppression of polychemotherapy-related HBV reactivation by
      entecavir administered as a prompt antiviral therapy in the cases of two patients
      with chronic lymphocytic leukemia and invasive ductal carcinoma. A review of the
      literature is discussed. RESULTS: Entecavir produced a rapid and sustained
      suppression of polychemotherapy-related HBV reactivation as a prompt antiviral
      therapy in the cases of two patients with chronic lymphocytic leukemia and
      invasive ductal carcinoma. CONCLUSION: Allowing a rapid and sustained control of
      HBV replication, entecavir seems to be a promising drug for first-line prompt
      treatment of HBV reactivation in patients undergoing chemotherapy for
      hematological as well as solid organ malignancies, with safe long-term use
      enabling maintenance of resolved hepatitis.

PMID- 25076064
TI  - Multicenter study on the discontinuation and efficacy of chronic hepatitis C
      treatment in the Spanish penitentiary population (EPIBAND study).
AB  - OBJECTIVE: Imprisonment entails a golden opportunity for chronic hepatitis C
      treatment, as treatment adherence can easily be achieved in this setting. The
      objective of this study was to determine the proportion and causes of
      discontinuation of chronic hepatitis C therapy among the Spanish penitentiary
      population. METHODS: This is an observational, prospective multicenter study
      performed in 26 Spanish penitentiaries between October 2007 and December 2009.
      Patients with chronic hepatitis C who were undergoing treatment with pegylated
      interferon plus ribavirin in accordance with clinical practice were included. The
      primary variable in the study was the proportion of discontinuation of treatment
      for chronic hepatitis C. RESULTS: A total of 431 patients were included in this
      analysis (92.3% male; mean age, 37.9+/-6.3 years; 66.4% with high viral load;
      genotype 1, 51.0%; genotype 3, 35.7%; genotype 4, 11.8%; genotype 2, 1.4%;
      coinfected with HIV, 24.4%). The proportion of treatment discontinuation for
      chronic hepatitis C was 22.5% (n=97; 95% confidence interval: 18.65-26.75).
      Therapy discontinuation was more frequent during the first trimester of treatment
      (n=45; 46.4%), and release from prison was the most frequent cause for treatment
      discontinuation (n=35; 36.1% of discontinuations). Among 407 patients included in
      the efficacy analysis, sustained viral response was achieved in 52.1% (95%
      confidence interval: 47.12-57.02). CONCLUSION: Treatment discontinuation for
      chronic hepatitis C in the penitentiary setting is low. However, further efforts
      should be made to improve the coordination between penitentiary institutions and
      external centers to ensure treatment after the inmates are released or
      transferred to other prisons.

PMID- 25076065
TI  - High prevalence of hepatitis markers in immigrant populations: a prospective
      screening approach in a real-world setting.
AB  - BACKGROUND: Immigrant populations are believed to be more frequently infected
      with hepatitis viruses. However, limited unbiased data are available on
      immigrants outside of academic centres. Therefore, the aim of this study was to
      perform large-scale screening for hepatitis markers in primary care centres
      treating mainly individuals with a migrational background in Germany. METHODS:
      Between November 2010 and January 2012, we prospectively screened 1313
      individuals treated by general practitioners at eight primary care centres in
      North-western Germany. Patients were eligible if they or their parents were not
      born in Germany. Serological screening for hepatitis B core protein antibodies,
      hepatitis B surface antigens (HBsAgs), and anti-hepatitis C virus antibodies was
      performed in each individual. HBsAg-positive and anti-hepatitis C virus-positive
      patients were further tested for molecular markers of viral replication. RESULTS:
      The mean age was 49.1+/-15.8 years. Of the patients, 45.7% were male; 87.3% had
      migrated to Germany from the Eastern Mediterranean area and 12.0% from Eastern
      Europe. Of the patients, 32.5% tested positive for hepatitis B core protein
      antibodies. HBsAgs were found in 3.6% of patients. Overall, hepatitis B virus DNA
      was detected in 2.2% of patients. Markers for hepatitis C virus infection were
      found in an almost similar high frequency (1.9%). Individuals with migrational
      background showed significant deficits in knowledge on general routes of
      transmission. CONCLUSION: Hepatitis virus infections are indeed significantly
      more prevalent in immigrant populations as compared with the general German
      population. These data underline the importance of introducing screening programs
      in this particular risk group.

PMID- 25076067
TI  - Clinical translation in the virtual liver network.
AB  - The liver is the central detoxifying organ, continuously removing xenobiotics
      from the vascular system. Given its role in drug metabolism, a functional
      understanding of liver physiology is crucial to optimizing drug efficacy and
      patient safety. The Virtual Liver Network (VLN), a German national flagship
      research program, focuses on producing validated computer models of human liver
      physiology. These models are used to analyze patient-derived data and thereby
      gain mechanistic insights in the processes underlying drug pharmacokinetics (PK).

PMID- 25076066
TI  - Prevalence, investigational pathways and diagnostic outcomes in differing
      irritable bowel syndrome subtypes.
AB  - BACKGROUND: There has been increasing interest in subclassifying irritable bowel
      syndrome (IBS) to make a positive diagnosis. AIM: The aim of this study was to
      assess the population prevalence of differing subtypes, investigational pathways
      and diagnostic outcomes. MATERIALS AND METHODS: Data were prospectively collected
      from three groups between 2005 and 2012. Group 1 [n=1002, 55% female, mean age 39
      years (range 16-93 years)] comprised healthy volunteers who were interviewed
      using the Rome III diagnostic questionnaire. In secondary care, group 2 [n=64,
      80% female, mean age 44 years (range 23-79 years)] comprised patients with
      constipation-predominant IBS (IBS-C) and group 3 [n=333, 66% female, mean age 51
      years (range 23-92 years)] comprised patients with diarrhoea-predominant IBS (IBS
      D). In groups 2 and 3, demographic data and diagnostic yield of investigations
      were evaluated as per normal clinical practice. RESULTS: IBS prevalence in group
      1 was 6% (60/1002). IBS-C patients were significantly older than those with IBS-D
      (mean age 45 vs. 30 years, P=0.027). In groups 2 and 3, patients with IBS-C
      underwent a total of 56 additional investigations (mean 0.88 per patient), which
      was significantly lower than the number of investigations undertaken in the IBS-D
      group of 734 (mean 2.2 per patient, P<0.001). Further investigations in group 3
      (IBS-D) identified an alternative diagnosis in 22%, whereas in group 2 (IBS-C)
      this was 0% (P<0.0001). CONCLUSION: This is the first study to evaluate the
      population prevalence of different IBS subtypes within a UK population. Although
      further investigations in IBS-D patients have led to alternative diagnoses, none
      were identified in the IBS-C population. The merits of investigating IBS-C
      patients should be questioned.

PMID- 25076068
TI  - Behavioral and electrophysiological measures of the body inversion effect: the
      contribution of the limb configurations.
AB  - Previous behavioral and electrophysiological studies examining the body inversion
      effect, where inversion of a body stimulus reduces its recognition, suggested
      that information regarding human bodies is processed configurally. However, few
      studies to date have examined how the magnitude of the body inversion effect may
      be impacted by varying degrees of configural information present in a stimulus of
      interest. In the current study, upright and inverted body stimuli were presented
      across three body posture conditions, the whole body, piecemeal body (without
      head and trunk), and random body posture conditions, while response times, error
      rates, and event-related potentials were recorded. Behavioral measures and
      assessment of the N170 component, particularly at occipital-temporal site,
      revealed a robust difference between upright and inverted postures for both the
      whole body and piecemeal body posture conditions, which was not observed in the
      random body posture condition. The behavioral measure showed less errors and
      faster reaction times for upright compared with inverted orientation; however,
      the N170 component only showed typical effect of orientation (more negative and
      more delayed peak in waveform for the inverted compared with upright orientation)
      in the left hemisphere. The magnitude and direction of these differences were
      comparable for whole body and piecemeal postures. Overall, these results were
      consistent with the notion that it is the first-order information of body posture
      rather than the presence of the head (and trunk) that determines the body
      inversion effect. 

PMID- 25076069
TI  - [Low-intensity pulsed ultrasound for treatment of fractures and nonunions -
      current evidence and insights from basic research and clinical application].
AB  - In Germany, 800,000 fractures are treated per year, and up to 10 % of these
      patients may suffer subsequently from a delayed union or a nonunion at the
      fracture site. Surgical treatment of these complications is tedious and
      associated with high costs. Therefore non-operative treatment is recently
      receiving more scientific and clinical attention. The adjuvant treatment with
      ultrasound has been propagated for the past years to enhance fracture healing and
      bony union, and has been discussed controversially. This review article
      demonstrates the significance of the low intensity pulsed ultrasound application
      in fracture treatment, on the basis of basic science results, animal experiments
      and the results of clinical trials. 

PMID- 25076071
TI  - Cyclopropanation of styrenes and stilbenes using lithiomethyl trimethylammonium
      triflate as methylene donor.
AB  - Lithiomethyl trimethylammonium triflate, prepared from tetramethylammonium
      triflate, cyclopropanates several styrenes and stilbenes with electron-donating
      and selected electron-withdrawing substituents efficiently. Kinetic data support
      a stepwise nucleophilic addition-ring closure mechanism for this methylenation. 

PMID- 25076070
TI  - Input sources of third person singular -s inconsistency in children with and
      without specific language impairment.
AB  - We tested four predictions based on the assumption that optional infinitives can
      be attributed to properties of the input whereby children inappropriately extract
      non-finite subject-verb sequences (e.g., the girl run) from larger input
      utterances (e.g., Does the girl run? Let's watch the girl run). Thirty children
      with specific language impairment (SLI) and thirty typically developing children
      heard novel and familiar verbs that appeared exclusively either in utterances
      containing non-finite subject-verb sequences or in simple sentences with the verb
      inflected for third person singular -s. Subsequent testing showed strong input
      effects, especially for the SLI group. The results provide support for input
      based factors as significant contributors not only to the optional infinitive
      period in typical development, but also to the especially protracted optional
      infinitive period seen in SLI.

PMID- 25076072
TI  - [Association between breast arterial calcifications and cardiovascular risk
      factors in menopausal women].
AB  - PURPOSE: To analyze associations between mammographic arterial mammary
      calcifications in menopausal women and risk factors for cardiovascular disease.
      METHODS: This was a cross-sectional retrospective study, in which we analyzed the
      mammograms and medical records of 197 patients treated between 2004 and 2005.
      Study variables were: breast arterial calcifications, stroke, acute coronary
      syndrome, age, obesity, diabetes mellitus, smoking, and hypertension. For
      statistical analysis, we used the Mann-Whitney, chi2 and Cochran-Armitage tests,
      and also evaluated the prevalence ratios between these variables and mammary
      artery calcifications. Data were analyzed with the SAS version 9.1 software.
      RESULTS: In the group of 197 women, there was a prevalence of 36.6% of arterial
      calcifications on mammograms. Among the risk factors analyzed, the most frequent
      were hypertension (56.4%), obesity (31.9%), smoking (15.2%), and diabetes
      (14.7%). Acute coronary syndrome and stroke presented 5.6 and 2.0% of prevalence,
      respectively. Among the mammograms of women with diabetes, the odds ratio of
      mammary artery calcifications was 2.1 (95%CI 1.0-4.1), with p-value of 0.02. On
      the other hand, the mammograms of smokers showed the low occurrence of breast
      arterial calcification, with an odds ratio of 0.3 (95%CI 0.1-0.8). Hypertension,
      obesity, diabetes mellitus, stroke and acute coronary syndrome were not
      significantly associated with breast arterial calcification. CONCLUSION: The
      occurrence of breast arterial calcification was associated with diabetes mellitus
      and was negatively associated with smoking. The presence of calcification was
      independent of the other risk factors for cardiovascular disease analyzed.

PMID- 25076073
TI  - [Causes of maternal death in Para State, Brazil].
AB  - PURPOSE: To identify the major causes of maternal death in the State of Para,
      Brazil. METHODS: A descriptive, observational and retrospective study was
      conducted using data from the Mortality Information System (SIM) of the State
      Department of Public Health of Para. SIM information was obtained using the
      TabWin 3.2 software and recorded in a research protocol developed by the
      investigators. The sample included 383 maternal deaths of 10-49-year-old women,
      which occurred from 2006 to 2010. Data were analyzed using non-parametric tests
      (chi2 and G-tests). The BioStat(r) 5.0 software was used for statistical analysis
      and Microsoft(r) Excel 2007 for the preparation of database and tables. RESULTS:
      The Maternal Mortality Ratio was 51.9 and did not decrease significantly during
      the period. Most deaths occurred during the postpartum period (up to 42 days)
      (51.7%), and some diagnostic confirmation was used. Direct obstetric causes were
      dominant (90.6%), mainly hypertension (34.6%), with emphasis on eclampsia (70%),
      and hemorrhage (22.2%). All of these maternal deaths were avoidable (100%).
      CONCLUSION: Maternal death in Para is characterized by occurring during the
      puerperium (up to 42 days), due mainly to direct obstetric causes, such as
      hypertension, with emphasis on eclampsia, and hemorrhage. This evidences the need
      for complete attention with good quality for pregnant women, from prenatal care
      to puerperium, in the state of Para.

PMID- 25076074
TI  - The impact of glycosylated hemoglobin and diabetes mellitus on wound-healing
      complications and infection after foot and ankle surgery.
AB  - BACKGROUND: The relationship between hyperglycemia and adverse outcomes after
      surgery has been widely documented. Long-term glucose control has been recognized
      as a risk factor for postoperative complications. In the foot and ankle
      literature, long-term glycemic control as a potential perioperative risk factor
      is not well studied. Our goal was to investigate whether hemoglobin A1c (HbA1c)
      level was independently associated with postoperative complications in a
      retrospective cohort study. METHODS: Three hundred twenty-two patients with a
      diagnosis of diabetes mellitus were enrolled in the study to assess risk factors
      associated with postoperative foot and ankle surgery complications. RESULTS:
      Bivariate analyses showed that HbA1c level and having at least one comorbidity
      were associated with postoperative infections. However, after adjusting for other
      covariates, the only significant factor was HbA1c level, with each increment of
      1% increasing the odds of infection by a factor of 1.59 (95% confidence interval
      [CI], 1.28-1.99). For postoperative wound-healing complications, bivariate
      analyses showed that body mass index, having at least one comorbidity, and HbA1c
      level were significant factors. After adjusting for other covariates, the only
      significant factors for developing postoperative wound complications were having
      at least one comorbidity (odds ratio, 2.03; 95% CI, 1.22-3.37) and HbA1c level
      (each 1% increment) (odds ratio, 1.25; 95% CI, 1.02-1.53). CONCLUSIONS: In this
      retrospective study, HbA1c level had the strongest association with postoperative
      foot and ankle surgery complications in patients with diabetes.

PMID- 25076075
TI  - Molecular determination of mixed infections of dermatophytes and nondermatophyte
      molds in individuals with onychomycosis.
AB  - BACKGROUND: Reports of mixed infections with nondermatophyte molds (NDMs) and
      dermatophytes in onychomycosis are rare, possibly owing to the inhibition of NDM
      growth during traditional culture. We sought to determine the prevalence of mixed
      infections in onychomycosis using molecular identification. METHODS: Molecular
      analyses were used to identify infecting organisms directly from at least two
      serial great toenail samples from each of the 44 patients. RESULTS: Mixed
      infections were present in 41% of the patients (18 of 44). A single coinfecting
      NDM was the most common mixed infection and was detected in 34% of patients with
      onychomycosis (15 of 44), with Fusarium oxysporum present in 14% (6 of 44),
      Scopulariopsis brevicaulis in 9% (4 of 44), Acremonium spp in 2% (1 of 44),
      Aspergillus spp in 4.5% (2 of 44), and Scytalidium spp in 4.5% (2 of 44). Mixed
      infections with two NDMs were found in 7% of patients (3 of 44). CONCLUSIONS:
      Mixed onychomycosis infections may be more prevalent than previously reported.

PMID- 25076076
TI  - A systematic review of ultrasound-guided and non-ultrasound-guided therapeutic
      injections to treat Morton's neuroma.
AB  - BACKGROUND: Morton's neuroma is a frequently painful condition of the forefoot,
      causing patients to seek medical care to alleviate symptoms. A plethora of
      therapeutic options is available, some of which include injection therapies.
      Researchers have investigated injection therapy for Morton's neuroma, and
      latterly the evidence base has been augmented with methods that use diagnostic
      ultrasound as a vehicle to deliver the injectate under image guidance for
      additional accuracy. To date, there seems to be no consensus that ultrasound
      guided injections provide better therapeutic outcomes than nonguided injections
      for the treatment of Morton's neuroma. METHODS: A systematic review was chosen
      because this method can undertake such a process. The review process identified
      13 key papers using predetermined inclusion and exclusion criteria, which then
      underwent methodological quality assessment using a pretested Quality Index. A
      narrative synthesis of the review findings is presented in light of the
      heterogeneity of the data from the extraction process. RESULTS: This systematic
      review provides an argument that ultrasound guidance can produce better short-
      and long-term pain relief for corticosteroid injections, can reduce the need for
      additional procedures in a series of sclerosing alcohol injections, can reduce
      the surgical referral rate, and can add efficacy to a single injection.
      CONCLUSIONS: Ultrasound guidance should be considered for injection therapy in
      the management of Morton's neuroma.

PMID- 25076077
TI  - Medial longitudinal arch mechanics before and after a 45-minute run.
AB  - BACKGROUND: Medial longitudinal arch integrity after prolonged running has yet to
      be well documented. We sought to quantify changes in medial longitudinal arch
      kinematics before and after a 45-min run in healthy recreational runners.
      METHODS: Thirty runners performed barefoot seated, standing, and running trials
      before and after a 45-min shod treadmill run. Navicular displacement, arch
      lengthening, and the arch height index were used to quantify arch deformation,
      and the arch rigidity index was used to quantify arch stiffness. RESULTS: There
      were no statistically significant differences in mean (95% confidence interval)
      values for navicular displacement (5.6 mm [4.7-6.4 mm]), arch lengthening (3.2 mm
      [2.6-3.9 mm]), change in arch height index (0.015 [0.012-0.018]), or arch
      rigidity index (0.95 [0.94-0.96]) after the 45-min run (all multivariate analyses
      of variance P >= .065). CONCLUSIONS: Because there were no statistically
      significant changes in arch deformation or rigidity, the structures of a healthy,
      intact medial longitudinal arch are capable of either adapting to cyclical
      loading or withstanding a 45-min run without compromise.

PMID- 25076078
TI  - Dynamic in vivo subtalar joint kinematics measured using a skin marker-based
      protocol a face validity study.
AB  - BACKGROUND: The subtalar joint allows complex motion of the foot relative to the
      leg, the analysis of which has presented a major challenge for researchers. The
      considerable interpatient variation in structure and function of the subtalar
      joint highlights the importance of developing a protocol to assess the kinematics
      in individuals rather than developing an overarching description of function. The
      use of skin-mounted markers is, therefore, preferable, allowing the noninvasive
      collection of data. We sought to assess the face validity of a skin-mounted
      marker-based protocol to measure the in vivo kinematics of the subtalar joint.
      METHODS: Thirty participants were recruited using minimal exclusion criteria. A
      previously tested skin-mounted marker placement protocol was used in conjunction
      with two CODA MPX 30 sensors to capture data during walking. The data produced
      were compared with those from previous studies that used bone-mounted markers.
      RESULTS: The results in all three planes represented feasible outcomes compared
      with those of previous studies, the data falling within the ranges published.
      Patterns of movement demonstrated are similar to, although not the same as, those
      shown by previous investigations. CONCLUSIONS: This study did not produce
      patterns of movement that exactly matched those of previous investigations. The
      results were, however, within the ranges previously published, and the patterns
      of movement shown were feasible. The results suggest the face validity of the
      method as a means of assessing the in vivo kinematics of the subtalar joint
      during the stance phase of gait.

PMID- 25076079
TI  - The subtalar joint axis palpation technique part 2: reliability and validity
      results using cadaver feet.
AB  - BACKGROUND: Clinically locating the point of no rotation to determine the
      subtalar joint axis location by applying pressure on the plantar surface of the
      foot was described by Kirby in 1987 but was never validated. We sought to extend
      a previously validated mechanical model to cadaver feet and to examine the
      intratester and intertester reliability. METHODS: Four testers with different
      levels of experience determined the subtalar joint axis location and moved the
      subtalar joint through its range of motion, capturing the movement using
      kinematic analysis. The comparison of the spatial subtalar joint axis location as
      determined by palpation between and within testers determined the intertester and
      intratester reliability. The helical axis method was performed to validate the
      model. RESULTS: The intrarater reliability varied from a high of alpha = 0.96 to
      a low of alpha = 0.26 for the slope and was, in general, high (alpha = 0.78-0.95)
      for the intersection. The interrater reliability scored moderate to high,
      depending on the specific cadaver specimen. Concerning the exact location of the
      subtalar joint axis, no significant difference was found between the results
      determined by different testers and the helical axis method. CONCLUSIONS: The
      palpation technique as part of the subtalar joint axis location and rotational
      equilibrium theory proposed by Kirby is a reliable and valid clinical tool.
      Experience in performing the palpation technique has a positive influence on the
      accuracy of the results. In the context of evidence-based practice, this
      technique could be a standard tool in the examination of patients with lower-limb
      related pathologic disorders.

PMID- 25076081
TI  - Personalized orthoses as a good treatment option for Charcot neuro
      osteoarthropathy of the foot.
AB  - BACKGROUND: We sought to assess the biomechanical characteristics of the feet of
      patients with Charcot neuro-osteoarthropathy and to determine reulceration rates
      before and after personalized conservative orthotic treatment. METHODS: A
      longitudinal prospective study was performed in 35 patients with Charcot's foot.
      Although some patients had a history of ulcers, at the study outset no patient
      had ulcers. All of the patients underwent biomechanical testing and a
      radiographic study. A radiophotopodogram was prepared by superimposing an imprint
      of the sole on a plantar radiograph. Based on the results of these tests, an
      orthopedic insole was prepared and therapeutic footwear prescribed for each foot.
      The following variables were compared between the Charcot and unaffected feet:
      previous ulcers and ulcer sites, reulcerations produced after treatment, type of
      foot (neuropathic/neuroischemic), ankle mobility, first-ray mobility, and relaxed
      calcaneal stance position. Treatment efficacy was determined by comparing ulcers
      presenting in patients in the year leading up to the study period and the year in
      which treatment was received. RESULTS: In a 1-year period, 70 feet received
      orthotic treatment, of which 41 were Charcot's feet. Ulceration rates before the
      study were 73.2% in feet with Charcot's and 31.0% in those without. After 1 year
      of wearing the customized orthoses, rates fell significantly to 9.8% in the
      Charcot feet and 0% in the feet without this condition. CONCLUSIONS: Conservative
      customized orthotic treatment was effective at preventing ulcers and the
      complications that often lead these patients to surgery.

PMID- 25076082
TI  - Primary closure of elective toe amputations in the diabetic foot--is it safe?
AB  - BACKGROUND: Toe amputation is the most common partial foot amputation.
      Controversy exists regarding whether to primarily close toe amputations or to
      leave them open for secondary healing. The purpose of this study was to evaluate
      the results of closed toe amputations in diabetic patients, with respect to wound
      healing, complications, and the need for further higher level amputation.
      METHODS: We retrospectively reviewed the results of 40 elective or semi-elective
      toe amputations with primary closure performed in 35 patients treated in a
      specialized diabetic foot unit. Patients with abscesses or necrotizing fasciitis
      were treated emergently and were excluded. Patients in whom clean margins could
      not be achieved due to extensive cellulitis or tenosynovitis and patients
      requiring vascular intervention were excluded as well. Outcome endpoints included
      wound healing at 3 weeks, delayed wound healing, or subsequent higher level
      amputation. RESULTS: Out of 40 amputations, 38 healed well. Thirty amputations
      healed by the time of stitch removal at 3 weeks and eight had delayed healing. In
      two patients the wounds did not heal and subsequent higher level amputation was
      eventually required. CONCLUSIONS: In carefully selected diabetic foot patients,
      primary closure of toe amputations is a safe surgical option. We do not recommend
      primary closure when infection control is not achieved or in patients requiring
      vascular reconstruction. Careful patient selection, skillful assessment of
      debridement margins and meticulous technique are required and may be offered by
      experienced designated surgeons in a specialized diabetic foot unit.

PMID- 25076083
TI  - Podiatric physicians' perspectives on their role in promoting self-care in high
      risk patients with diabetes.
AB  - BACKGROUND: Foot self-care is key in preventing morbidity in high-risk diabetic
      patients. Motivational interviewing (MI) is an approach to encourage behavior
      change by patients that can be used in medical settings. The goal was to explore
      how podiatric physicians promote self-care in such patients and whether they use
      MI techniques. METHODS: We conducted a 19-question online survey of US-based
      practicing podiatric physicians. Most answers were on a 5-point scale. The MI
      index was the sum of answers to five relevant questions. RESULTS: Of 843
      podiatric physicians, 86% considered foot self-care to be very important for high
      risk diabetic patients, and 90% felt that it was their role to discuss foot self
      care with them; 49% felt that they had training and were successful in promoting
      behavior change, but most were definitely (38%) or possibly (46%) interested in
      learning more. Only 24% of respondents scored at least 15 of 20 on the MI index.
      Higher MI scores were associated with more face time and more time discussing
      foot self-care but were not related to podiatric physicians' age, sex, geographic
      location, percentage of time in surgery, or years in practice. Reported barriers
      to counseling were lack of reimbursed time and poor patient engagement.
      CONCLUSIONS: Most podiatric physicians view self-care behavior among high-risk
      diabetic patients and their role in promoting it as very important; most feel
      already proficient, but only a few demonstrate MI skills; most are willing to
      learn more. Success in behavioral counseling, such as MI, is likely to require
      more time and may be encouraged by a move from fee-for-service to outcome-based
      reimbursement.

PMID- 25076084
TI  - Needling versus liquid nitrogen cryotherapy for the treatment of pedal warts a
      randomized controlled pilot study.
AB  - BACKGROUND: We hypothesized that needling of a pedal wart creates local
      inflammation and a subsequent cell-mediated immune response (CMIR) against human
      papillomavirus. The primary objective of this study was to investigate whether
      needling to induce a CMIR against human papillomavirus is an effective treatment
      for pedal warts compared with liquid nitrogen cryotherapy. A secondary objective
      was to investigate whether the CMIR induced by needling is effective against
      satellite pedal warts. METHODS: Eligible patients with pedal warts were randomly
      allocated to receive either needling or liquid nitrogen cryotherapy. Only the
      primary pedal wart was treated during the study. Follow-up was 12 weeks, with
      outcome assessments made independently under blinded circumstances. RESULTS: Of
      37 patients enrolled in the study, 18 were allocated to receive needling and 19
      to receive liquid nitrogen cryotherapy. Regression of the primary pedal wart
      occurred in 64.7% of the needling group (11 of 17) and in 6.2% of the liquid
      nitrogen cryotherapy group (1 of 16) (P =  .001). No significant relationship was
      found between needling of the primary pedal wart and regression of satellite
      pedal warts (P = .615) or complete pedal wart regression (P = .175). There was no
      significant difference in pain, satisfaction, or cosmesis between the two groups.
      CONCLUSIONS: The regression rate of the primary pedal wart was significantly
      higher in the needling group compared with the liquid nitrogen cryotherapy group.

PMID- 25076085
TI  - Radiographic anatomy of the foot and ankle--part 1: the distal leg.
AB  - The normal radiographic anatomy of the foot and ankle, aside from my previous
      work, has been addressed only superficially or sparingly in the medical
      literature. This project correlates the detailed radiographic anatomy of the
      entire adult foot and ankle (two-dimensional) to osteology (three-dimensional).
      Each bone's position was determined after meticulous examination and correlation
      to an articulated skeleton relative to the image receptor and direction of the x
      ray beam, with correlation to the radiograph for confirmation. Images of each
      foot and distal leg bone ("front" and "back" perspectives) are presented
      alongside a corresponding radiographic image for comparison. The normal gross and
      radiographic anatomy is correlated and described for each radiographic
      positioning technique. Foundational knowledge is provided that future researchers
      can use as a baseline ("normal") and that students and practitioners can use for
      comparison when interpreting radiographs and distinguishing abnormal findings.
      The findings from the original project, owing to its broad scope, have been
      divided into five parts: the lower leg (the focus of this paper), the greater
      tarsus, the lesser tarsus, the metatarsals, and the phalanges. 

PMID- 25076086
TI  - Digital and interdigital corns: a report of two cases with use of hyaluronic acid
      gel filler.
AB  - Digital and interdigital corns are common painful foot conditions encountered by
      podiatrists during the course of their practice. These corns can often be treated
      with conservative techniques, although they tend to eventually recur. Currently,
      no single treatment exists that is efficient, long-lasting, minimally invasive,
      and easy to administer. This article describes two cases where hyaluronic acid
      gel injections were used to improve symptoms associated with digital and
      interdigital corns located in a nonweightbearing area. Both patients tolerated
      the intervention well and showed considerable improvement of their condition for
      a substantial period of time after the intervention without developing adverse
      reactions. Hyaluronic acid gel injections could very well represent an
      interesting therapeutic alternative for digital and interdigital corns located in
      nonweightbearing areas. 

PMID- 25076087
TI  - Exertional compartment syndrome of the medial foot compartment--diagnosis and
      treatment: a case report.
AB  - Exertional compartment syndrome in the foot is rarely reported and often confused
      with plantar fasciitis as a cause of arch pain in the running athlete. We
      describe a case involving a 19-year-old competitive collegiate runner who
      developed a chronic case of bilateral medial arch pain during training, which was
      initially diagnosed as plantar fasciitis but failed to respond to conventional
      treatment. After symptoms began to suggest exertional compartment syndrome, the
      diagnosis was confirmed by measuring an elevated resting pressure in the medial
      compartment of both feet. The patient underwent a bilateral medial compartment
      fasciotomy, which allowed a full return to activity, and has remained pain free
      after a 1-year follow-up. 

PMID- 25076088
TI  - Merkel cell carcinoma of the lower extremity: a case report.
AB  - Merkel cell carcinoma is a rare, often fatal, neuroendocrine cutaneous malignancy
      with a highly variable clinical presentation. Due to the rapid progression of the
      disease, early detection and treatment is vital to survival. Here, we report the
      case of a 45-year-old woman whose podiatrist noticed an unusual lesion on her
      lower left leg and referred her to a dermatologist for work-up. A diagnostic
      excisional biopsy confirmed the diagnosis and was followed by treatment that
      included wide local excision of the primary lesion with subsequent chemotherapy
      and radiation. At the time of diagnosis, sentinel lymph node biopsy was positive.
      Due to the increasing prevalence of Merkel cell carcinoma in the past decade and
      its propensity to present on the lower extremity, podiatric physicians need to be
      aware of the clinical presentation and treatment guidelines for this elusive
      disease.

PMID- 25076089
TI  - Congenital onychoheterotopia involving multiple toe nails.

PMID- 25076090
TI  - JAPMA: gold, not mold.

PMID- 25076095
TI  - Gas-phase energy of the S2<-S0 transition and electrostatic properties of the S2
      state of carotenoid peridinin via a solvatochromic shift and orientation
      broadening of the absorption spectrum.
AB  - The solvent effect on the position and the shape of the absorption spectrum of
      peridinin for 12 protic and aprotic solvents as well as the temperature effect
      for methanol were studied using a solvatochromic theory based on the Onsager
      sphere cavity model. (Experimental data have been provided by T. Polivka and V.
      Sundstrom.) Solvatochromic calculations combined with estimations of orientation
      broadening of the absorption spectrum by convolution allowed the conclusion that
      the orientation (dipole-dipole), induction and dispersion solute-solvent
      interactions reasonably describes the position of the 0-0 frequency. The
      orientation interactions led to the blue solvatochromic shift, separating them
      from the induced and dispersion interactions, which produce a red shift. The FWHM
      of Gaussian of inhomogeneous broadening originated from the fluctuations of
      orientation interactions was demonstrated to be high (945 cm(-1)) even for such a
      nonpolar solvent as hexane. The value of |DeltaMU|/cos phi of -18.7 D has been
      found (DeltaMU = MU2 - MUg, phi is the angle between DeltaMU and MUg). By
      assigning peridinin to the idealized C2v point group, the large change of dipole
      moment |DeltaMU| of 18.7 D under S2<-S0 transition is obtained for peridinin in
      gas phase. Moreover, the S2-excited state dipole moment MU2 has the opposite
      orientation relative to that at the ground S0 state MUg. The determined gas-phase
      0-0 energy of the S2<-S0 transition, 22 910 cm(-1) (2.84 eV) is employed to
      calculate the polarizability change between the S0 and S2 states of 376 A(3). The
      finding for the effective Onsager radius is of 9.4 A. Obtained results for
      electrostatic properties of the S2 state are compared with those known from Stark
      spectroscopy and quantum-mechanical calculations. 

PMID- 25076096
TI  - Phonetic imitation by young children and its developmental changes.
AB  - PURPOSE: In the current study, the author investigated the developmental course
      of phonetic imitation in childhood, and further evaluated existing accounts of
      phonetic imitation. METHOD: Sixteen preschoolers, 15 third graders, and 18
      college students participated in the current study. An experiment with a modified
      imitation paradigm with a picture-naming task was conducted, in which
      participants' voice-onset time (VOT) was compared before and after they were
      exposed to target speech with artificially increased VOT. RESULTS: Extended VOT
      in the target speech was imitated by preschoolers and 3rd graders as well as
      adults, confirming previous findings in phonetic imitation. Furthermore, an age
      effect of phonetic imitation was observed; namely, children showed greater
      imitation than adults, whereas the degree of imitation was comparable between
      preschoolers and 3rd graders. No significant effect of gender or word specificity
      was observed. CONCLUSIONS: Young children imitated fine phonetic details of the
      target speech, and greater degree of phonetic imitation was observed in children
      compared to adults. These findings suggest that the degree of phonetic imitation
      negatively correlates with phonological development.

PMID- 25076097
TI  - Modeling and analysis of transport in the mammary glands.
AB  - The transport of three toxins moving from the blood stream into the ducts of the
      mammary glands is analyzed in this work. The model predictions are compared with
      experimental data from the literature. The utility of the model lies in its
      potential to improve our understanding of toxin transport as a pre-disposing
      factor to breast cancer. This work is based on a multi-layer transport model to
      analyze the toxins present in the breast milk. The breast milk in comparison with
      other sampling strategies allows us to understand the mass transport of toxins
      once inside the bloodstream of breastfeeding women. The multi-layer model
      presented describes the transport of caffeine, DDT and cimetidine. The analysis
      performed takes into account the unique transport mechanisms for each of the
      toxins. Our model predicts the movement of toxins and/or drugs within the mammary
      glands as well as their bioaccumulation in the tissues. 

PMID- 25076098
TI  - Bis(subphthalocyanine)-azaBODIPY triad for ultrafast photochemical processes.
AB  - Multi-modular supramolecular systems capable of undergoing photoinduced energy
      and electron transfer are of paramount importance to design light-to-energy and
      light-to-fuel converting devices. Often, this has been achieved by linking two or
      more photo-active or redox-active entities with complementary spectral and
      photochemical properties. In the present study, we report a new triad made out of
      two entities of subphthalocyanine covalently linked to BF2-chelated
      azadipyrromethene ((SubPc)2-azaBODIPY). The triad was fully characterized by
      spectral, computational, electrochemical and photochemical techniques. The
      B3LYP/6-31G* calculations revealed a structure wherein the donor, SubPc, and the
      acceptor, azaBODIPY, were well separated with no steric crowding. The different
      redox states were established from the differential pulse voltammetry studies and
      the data were used to estimate free-energy change associated with charge
      separation. Such calculations revealed the charge separation from either the
      (1)SubPc* or (1)azaBODIPY* to be thermodynamically feasible for yielding the
      (SubPc)SubPc(+)-azaBODIPY(-) radical ion-pair. Steady-state fluorescence studies
      revealed quantitative quenching of (1)SubPc* in the triad and solvent dependent
      quenching of (1)azaBODIPY* indicating participation of both fluorophores in
      promoting photochemical events. In nonpolar toluene, singlet-singlet energy
      transfer from the (1)SubPc* to azaBODIPY was observed, while in polar
      benzonitrile, evidence of energy transfer was feeble. Femtosecond laser flash
      photolysis studies provided concrete evidence for the occurrence of ultrafast
      photoinduced electron transfer by providing spectral proof for the formation of
      the (SubPc)SubPc(+)-azaBODIPY(-) charge separated state. The charge recombination
      followed populating the (3)azaBODIPY* prior to returning to the ground state. 

PMID- 25076099
TI  - Local fasciocutaneous sliding flaps for soft-tissue defects of the dorsum of the
      hand.
AB  - IMPORTANCE: Appropriate coverage of defects that expose tendon, joints, and/or
      neurovascular structures is necessary to preserve optimal hand function. Local,
      random-pattern flaps and skin grafts may be inadequate because of the hand's
      finite skin reservoir or the presence of a poorly vascularized and mobile wound
      bed. Described herein is a novel method of dorsal hand reconstruction.
      OBSERVATIONS: A fasciocutaneous sliding flap and the underlying vascular anatomy
      of the dorsal hand are described. The flap takes advantage of the distinct
      fascial layers of the hand by raising the skin and fascia with bilevel
      undermining. CONCLUSIONS AND RELEVANCE: The proposed single-stage, bilevel
      undermined fasciocutaneous sliding flap based on the perforating vessels running
      through fascial septae recruits pliable, easily mobilized skin, preserves
      neurosensory innervation, and facilitates early hand mobilization with reduced
      postoperative care. This flap, and its proposed variations, are ideal for use
      when paratenon is exposed and immobilizing the hand would be necessary for graft
      survival or when tension at the wound precludes reconstruction with primary
      closure or a traditional flap.

PMID- 25076101
TI  - Relief of cancer pain by glycine transporter inhibitors.
AB  - BACKGROUND: Recent studies have revealed the antinociceptive effects of glycine
      transporter (GlyT) inhibitors in neuropathic pain models such as sciatic nerve
      injured and diabetic animals. Bone cancer can cause the most severe pain
      according to complex mechanisms in which a neuropathic element is included. Bone
      cancer modifies the analgesic action of opioids and limits their effectiveness,
      and thus novel medicament for bone cancer pain is desired. METHODS: For the femur
      bone cancer model, NCTC 2472 tumor cells were injected into the medullary cavity
      of the distal femur of C3H/HeN mice. Effects of GlyT2 inhibitors, ORG 25543 and
      ALX 1393, and GlyT1 inhibitors, ORG 25935, and knockdown of the expression of
      spinal GlyTs protein by GlyTs siRNA on pain-like behaviors, such as allodynia,
      withdrawal threshold, guarding behavior, and limb-use abnormality, were examined
      in the femur bone cancer model mice. Effects of morphine in combination with GlyT
      inhibitor were examined. RESULTS: GlyT2 inhibitors, ORG 25543 and ALX 1393, and
      GlyT1 inhibitor ORG 25935 by IV or oral administration or knockdown of the
      expression of spinal GlyTs protein improved pain-like behaviors at 11 days after
      tumor transplantation. The pain-relief activity was potent and long lasting.
      Morphine at a dose with no analgesic activity combined with ORG 25543 further
      promoted the ORG 25543-induced pain-relief activity. Injection of ORG 25543 on
      the second day after tumor implantation caused 3 phases of pain responses; pain
      like behaviors were initially accelerated (at 2-4 days) and subsequently almost
      disappeared (5-7 days) and then reappeared. Intrathecal injection of strychnine 1
      day after injection of ORG 25543 transiently antagonized the pain-relief activity
      of ORG 25543. In control mice, strychnine improved pain-like behaviors 4 days
      after tumor implantation and aggravated the behaviors between 4 and 5 days. The
      evidence suggests that the different mechanisms are phase-dependently involved.
      CONCLUSIONS: GlyT inhibitors with or without morphine may be a new strategy for
      the treatment of bone cancer pain and lead to further investigations of the
      mechanisms underlying the development of bone cancer pain.

PMID- 25076100
TI  - Preoperative statin administration does not protect against early postoperative
      acute respiratory distress syndrome: a retrospective cohort study.
AB  - BACKGROUND: Statins have been shown to possess antiinflammatory and
      immunomodulatory effects. In this study, we sought to determine if preoperative
      statin therapy is associated with a reduced frequency of postoperative acute
      respiratory distress syndrome (ARDS) in surgical populations at increased risk of
      developing ARDS. METHODS: We performed a retrospective cohort evaluation of the
      association between preoperative statin therapy and early postoperative ARDS in
      patients undergoing elective high-risk thoracic and aortic vascular surgery. The
      association between preoperative statin therapy and postoperative ARDS was
      assessed using propensity-adjusted analyses to control for indication bias and
      confounding factors. RESULTS: Of 1845 patients, 722 were receiving preoperative
      statin therapy. One hundred twenty patients developed postoperative ARDS.
      Frequencies of ARDS among those receiving statin therapy versus those who were
      not was 7.2% and 6.1%, respectively (OR = 1.20; 95% CI, 0.83-1.75; P = 0.330).
      Neither the stratified propensity score analysis (pooled OR 0.93; 95% CI, 0.60
      1.43) nor matched analysis (OR = 0.78; 95% CI, 0.48-1.27) identified a
      statistically significant association between preoperative statin administration
      and postoperative ARDS. When compared to matched controls, patients who developed
      postoperative ARDS did not differ in mortality (7.7% vs 8.8%, P = 0.51), hospital
      length of stay (21 days vs 15 days, P = 0.21), or ventilator-free days (24 days
      vs 25 days, P = 0.62). CONCLUSIONS: In patients undergoing high-risk surgery,
      preoperative statin therapy was not associated with a statistically significant
      reduction in postoperative ARDS. These results do not support the use of statins
      as prophylaxis against ARDS in patients undergoing high-risk surgery.

PMID- 25076102
TI  - The safety of modern anesthesia for children with long QT syndrome.
AB  - BACKGROUND: Patients with long QT syndrome (LQTS) may experience a clinical
      spectrum of symptoms, ranging from asymptomatic, through presyncope, syncope, and
      aborted cardiac arrest, to sudden cardiac death. Arrhythmias in LQTS are often
      precipitated by autonomic changes. This patient population is believed to be at
      high risk for perioperative arrhythmia, specifically torsades de pointes (TdP),
      although this perception is largely based on limited literature that predates
      current anesthetic drugs and standards of perioperative monitoring. We present
      the largest multicenter review to date of anesthetic management in children with
      LQTS. METHODS: We conducted a multicentered retrospective chart review of
      perioperative management of children with clinically diagnosed LQTS, aged 18
      years or younger, who received general anesthesia (GA) between January 2005 and
      January 2010. Data from 8 institutions were collated in an anonymized database.
      RESULTS: One hundred three patients with LQTS underwent a total of 158 episodes
      of GA. The median (interquartile range) age and weight of the patients at the
      time of GA was 9 (3-15) years and 30.3 (15.4-54) kg, respectively. Surgery was
      LQTS-related in 81 (51%) GA episodes (including pacemaker, implantable
      cardioverter-defibrillator, and loop recorder insertions and revisions and lead
      extractions) and incidental in 77 (49%). beta-blocker therapy was administered to
      76% of patients on the day of surgery and 47% received sedative premedication.
      Nineteen percent of patients received total IV anesthesia, 30% received total
      inhaled anesthesia, and the remaining 51% received a combination. No patient
      received droperidol. There were 5 perioperative episodes of TdP, all in neonates
      or infants, all in surgery that was LQTS-related, and none of which was overtly
      attributable to anesthetic regimen. Thus the incidence (95% confidence interval)
      of perioperative TdP in incidental versus LQTS-related surgery was 0/77 (0%; 0%
      5%) vs 5/81 (6.2%; 2%-14%). CONCLUSIONS: With optimized perioperative management,
      modern anesthesia for incidental surgery in patients with LQTS is safer than
      anecdotal case report literature might suggest. Our series suggests that the risk
      of perioperative TdP is concentrated in neonates and infants requiring urgent
      interventions after failed first-line management of LQTS.

PMID- 25076103
TI  - Is any test 100% specific and 100% sensitive for serious injury?

PMID- 25076104
TI  - Development of new potato virus X-based vectors for gene over-expression and gene
      silencing assay.
AB  - Multiple plant viruses, including potato virus X (PVX), have been modified as
      vectors for expressing heterologous genes or silencing endogenous genes in
      plants. PVX-based vectors facilitate the functional analysis of genes in plant.
      However, they can only express one protein in a time. In this paper we report the
      construction of new vectors based on a 35S promoter-driven PVX infectious clone,
      pCaPVX100. Vector pCaPVX440 contains two additional subgenomic promoters and can
      be utilized to express two foreign genes at the same time. Plasmid pCaPVX760 is a
      CP minus vector and can be used to express foreign proteins through the gene
      substitution strategy. In addition, plasmid pCaPVX100 was engineered into a gene
      silencing vector (pCaPVX440-LIC) by introducing a ligation independent cloning
      (LIC) site into the vector. These results indicate that the newly developed PVX
      vectors are competent for multiple research purposes. 

PMID- 25076106
TI  - Towards understanding the color change of 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide during gamma irradiation: an experimental and
      theoretical study.
AB  - The application of room-temperature ionic liquids (RTILs) in nuclear spent fuel
      recycling requires a comprehensive knowledge of radiation effects on RTILs.
      Although preliminary studies indicate a relatively high radiation stability of
      RTILs, little attention is paid to the color change of RTILs, an obvious
      phenomenon of RTILs during irradiation. In this paper, we have investigated
      radiation-induced darkening and decoloration of 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([BMIm][NTf2]), an ionic liquid representing
      the most popular class of RTILs, by means of UV-Vis analysis and time-dependent
      density functional theory calculations. Based on the experimental and
      computational results, it is proposed that the color change of [BMIm][NTf2] upon
      irradiation originates from the formation of double bonds in the aliphatic chains
      of pristine organic cations (or radiolytic products of RTILs) and various
      associated species containing these "double-bond products". This work sheds light
      on the understanding of the radiation-induced color change of RTILs. 

PMID- 25076107
TI  - Structural network analysis of brain development in young preterm neonates.
AB  - Preterm infants develop differently than those born at term and are at higher
      risk of brain pathology. Thus, an understanding of their development is of
      particular importance. Diffusion tensor imaging (DTI) of preterm infants offers a
      window into brain development at a very early age, an age at which that
      development is not yet fully understood. Recent works have used DTI to analyze
      structural connectome of the brain scans using network analysis. These studies
      have shown that, even from infancy, the brain exhibits small-world properties.
      Here we examine a cohort of 47 normal preterm neonates (i.e., without brain
      injury and with normal neurodevelopment at 18 months of age) scanned between 27
      and 45 weeks post-menstrual age to further the understanding of how the
      structural connectome develops. We use full-brain tractography to find white
      matter tracts between the 90 cortical and sub-cortical regions defined in the
      University of North Carolina Chapel Hill neonatal atlas. We then analyze the
      resulting connectomes and explore the differences between weighting edges by
      tract count versus fractional anisotropy. We observe that the brain networks in
      preterm infants, much like infants born at term, show high efficiency and
      clustering measures across a range of network scales. Further, the development of
      many individual region-pair connections, particularly in the frontal and
      occipital lobes, is significantly correlated with age. Finally, we observe that
      the preterm infant connectome remains highly efficient yet becomes more clustered
      across this age range, leading to a significant increase in its small-world
      structure.

PMID- 25076108
TI  - Socioeconomic and environment determinants as predictors of severe malaria in
      children under 5 years of age admitted in two hospitals in Koudougou district,
      Burkina Faso: a cross sectional study.
AB  - Burkina Faso has a high incidence and death rate of severe malaria, especially
      for children under 5 years of age. Although the malaria elimination program is a
      high-priority public health project, finding an effective strategy for managing
      the problem is a major challenge. Understanding the various factors that
      contribute to the severity of malaria is essential in designing an effective
      strategy. In this study, parental and environmental factors associated with
      severe malaria in Burkinabe children were investigated in two hospitals in
      Koudougou Health District, Burkina Faso. Between July and September 2012, a cross
      sectional study was used to test 510 children under 5 years of age (mean age:
      23.5 months) admitted with suspected malaria. Each child was screened using a
      blood smear to identify whether he or she had severe malaria based on the
      criteria established by the World Health Organization (WHO). When a child was
      diagnosed with malaria, either severe or not severe, the parents were interviewed
      by a trained interviewer using a structured questionnaire. A logistic regression
      was used to identify the determinants of severe malaria and associated deaths. Of
      the 510 children having malaria, 201 (39.4%) had severe malaria. Most of the
      patients (54.9%) lived in rural areas. The main factors associated with severe
      malaria were low education level of the father, low socioeconomic status [odds
      ratio (OR)=4.11, 95% confidence interval (CI)=1.44-11.75], delayed treatment
      [OR=4.53, 95% CI=1.76-11.65], treating children at home as a typical practice
      when the child has a fever [OR=3.24, 95% CI=1.40-7.51], living in rural area
      [OR=6.66, 95% CI=3.36-13.22], and living beside a water gathering pond (OR=1.67,
      95% CI=1.02-2.74]. Parental and environmental context associated with severe
      malaria for children under 5 years of age remains a serious public health problem
      that affects malaria outcomes in resource-limited areas. Promotion of early care
      is urgently required. Parents should be given information on the risks of not
      consulting a health facility when children exhibit symptoms of malaria. 

PMID- 25076109
TI  - Anti-Trichinella IgG in ethnic minorities living in Trichinella-endemic areas in
      northwest Vietnam: study of the predictive value of selected clinical signs and
      symptoms for the diagnosis of trichinellosis.
AB  - The objective of this study was to assess the presence of anti-Trichinella IgG in
      the serum of persons from ethnic minorities from northwest Vietnam with clinical
      signs and symptoms that are compatible with trichinellosis. A total of 645
      persons were enrolled, of which 200 people lived in two villages where outbreaks
      of human trichinellosis had been documented in 2004 and 2008, and 445 people who
      were hospitalized in the Dien Bien and Son La provincial hospitals without a
      definitive diagnosis. Presence of anti-Trichinella IgG was demonstrated in serum
      samples by a standardized Enzyme-linked Immunosorbant Assay (ELISA); positive
      serum samples were subjected to Western blot (WB) for confirmation. Seven (3.5%;
      95% CI: 1.4-7.1) persons from the villages and seven (1.6%; 95% CI: 0.6-3.2)
      hospitalized patients, tested positive by both ELISA and WB. Fever (N=13),
      eosinophilia (N=12), myalgia (N=9), facial edema (N=9) and leukocytosis (N=8)
      were the most common clinical signs and symptoms in the serologically positive
      persons. The concomitant occurrence of facial edema and myalgia among the
      enrolled persons from the villages, accounted for 75% of the positive predictive
      value (PPV) and 99.5% of the negative predictive value (NPV), suggesting that
      they could be used for suspecting trichinellosis when serology is not available.
      The high prevalence (1.6-3.5%) of anti-Trichinella IgG in persons from Vietnamese
      provinces where Trichinella spiralis is circulating in pigs strongly supports the
      need to develop control programs to eliminate the infection from pigs and for
      consumers' education and protection. 

PMID- 25076110
TI  - Efficiency to reach age of puberty and behaviour of buffalo heifers (Bubalus
      bubalis) kept on pasture or in confinement.
AB  - In order to evaluate the influence of rearing system (free-ranging (FR) v.
      confinement (C)) on buffalo heifer efficiency to reach age of puberty and on
      behavioural and immune functions, two experiments were conducted from September
      2010 to October 2011. In Experiment I, 32 subjects aged 8 to 9 months at the
      start of experiment were used. A total of 16 animals (group C) were group housed
      in an indoor slatted floor pen (4 m2/animal) with an outdoor paddock (4
      m2/animal); 16 others grazed on a Mediterranean natural pasture of 40 ha (group
      FR). Behavioural data were collected and organic matter digestibility, blood
      metabolites and progesterone were determined. At the end of the experiment, a
      novel object test and a skin test were conducted, and the avoidance distance (AD)
      at the manger was measured. Free-ranging animals were able to express natural
      behaviours such as wallowing and grazing. C animals devoted more time to the
      novel object than FR animals, whereas AD at manger was lower in group FR than in
      group C (P<0.01). Cellular immune response was higher in FR heifers than in C
      animals (P<0.01). FR animals also showed a higher digestibility of organic matter
      (P<0.01). Heifers from group FR had higher plasma concentrations of non
      esterified fatty acids (P<0.001) and lower concentrations of glucose than heifers
      from group C (P<0.001). C animals showed higher daily weight gains (P<0.01) and
      weight at the puberty (P<0.05), but there were no differences in terms of age of
      puberty between the two groups. The intakes of dry matter (DM), CP and energy to
      reach the age of puberty were similar in both groups. In order to verify whether
      the results obtained in Experiment I could be replicated in different rearing
      conditions (reduced pasture availability, different location and altitude), a
      second experiment was conducted on 26 animals, where only onset of age of puberty
      and metabolic profile were monitored. In Experiment II, 13 heifers grazed on a
      natural pasture of 5 ha, other 13 received the same space as indicated for
      Experiment I. Results from Experiment II generally confirmed those of Experiment
      I. Only the intakes of DM and energy to reach the age of puberty were higher in
      group C than in FR (P<0.001). A lower competition with human nutrition,
      reproductive performances similar to those shown by confined animals and the
      indications given by immune and behavioural variables, suggest that a free-range
      based system may be conveniently used for buffalo heifer farming purposes. 

PMID- 25076111
TI  - Leptospirosis-associated hospitalizations, United States, 1998-2009.
AB  - A small percentage of persons with leptospirosis, a reemerging zoonosis,
      experience severe complications that require hospitalization. The number of
      leptospirosis cases in the United States is unknown. Thus, to estimate the
      hospitalization rate for this disease, we analyzed US hospital discharge records
      for 1998-2009 for the total US population by using the Nationwide Inpatient
      Sample. During that time, the average annual rate of leptospirosis-associated
      hospitalizations was 0.6 hospitalizations/1,000,000 population. Leptospirosis
      associated hospitalization rates were higher for persons >20 years of age and for
      male patients. For leptospirosis-associated hospitalizations, the average age of
      patients at admission was lower, the average length of stay for patients was
      longer, and hospital charges were higher than those for nonleptospirosis
      infectious disease-associated hospitalizations. Educating clinicians on the signs
      and symptoms of leptospirosis may result in earlier diagnosis and treatment and,
      thereby, reduced disease severity and hospitalization costs. 

PMID- 25076112
TI  - Fatal intracerebral haemorrhage secondary to Aspergillus arteritis following
      aneurysm clipping.
AB  - Cerebral aspergillosis is rare and presents a high mortality. We report a case of
      cerebral aspergillosis following elective clipping of an intracerebral aneurysm
      and review the literature surrounding the topic. Early diagnosis and aggressive
      treatment maximizes survival rates.

PMID- 25076113
TI  - The impact of restaurant consumption among US adults: effects on energy and
      nutrient intakes.
AB  - OBJECTIVE: To examine the effect of fast-food and full-service restaurant
      consumption on adults' energy intake and dietary indicators. DESIGN: Individual
      level fixed-effects regression model estimation based on two different days of
      dietary intake data was used. SETTING: Parallel to the rising obesity epidemic in
      the USA, there has been a marked upward trend in total energy intake derived from
      food away from home. SUBJECTS: The full sample included 12 528 respondents aged
      20-64 years who completed 24 h dietary recall interviews for both day 1 and day 2
      in the National Health and Nutrition Examination Survey (NHANES) 2003-2004, 2005
      2006, 2007-2008 and 2009-2010. RESULTS: Fast-food and full-service restaurant
      consumption, respectively, was associated with an increase in daily total energy
      intake of 813.75 kJ (194.49 kcal) and 858.04 kJ (205.21 kcal) and with higher
      intakes of saturated fat (3.48 g and 2.52 g) and Na (296.38 mg and 451.06 mg).
      Individual characteristics moderated the impacts of restaurant food consumption
      with adverse impacts on net energy intake being larger for black adults compared
      with their white and Hispanic counterparts and greater for middle-income v. high
      income adults. CONCLUSIONS: Adults' fast-food and full-service restaurant
      consumption was associated with higher daily total energy intake and poorer
      dietary indicators.

PMID- 25076114
TI  - Leukemogenesis in heterozygous PU.1 knockout mice.
AB  - Most murine radiation-induced acute myeloid leukemias involve biallelic
      inactivation of the PU.1 gene, with one allele being lost through a radiation
      induced chromosomal deletion and the other allele affected by a recurrent point
      mutation in codon 235 that is likely to be spontaneous. The short latencies of
      acute myeloid leukemias occurring in nonirradiated mice engineered with PU.1
      conditional knockout or knockdown alleles suggest that once both copies of PU.1
      have been lost any other steps involved in leukemogenesis occur rapidly. Yet,
      spontaneous acute myeloid leukemias have not been reported in mice heterozygous
      for a PU.1 knockout allele, an observation that conflicts with the understanding
      that the PU.1 codon 235 mutation is spontaneous. Here we describe experiments
      that show that the lack of spontaneous leukemia in PU.1 heterozygous knockout
      mice is not due to insufficient monitoring times or mouse numbers or the genetic
      background of the knockout mice. The results reveal that spontaneous leukemias
      that develop in mice of the mixed 129S2/SvPas and C57BL/6 background of knockout
      mice arise by a pathway that does not involve biallelic PU.1 mutation. In
      addition, the latency of radiation-induced leukemia in PU.1 heterozygous mice on
      a genetic background susceptible to radiation-induced leukemia indicates that the
      codon 235 mutation is not a rate-limiting step in radiation leukemogenesis driven
      by PU.1 loss. 

PMID- 25076115
TI  - Combinatorial DNA damage pairing model based on X-ray-induced foci predicts the
      dose and LET dependence of cell death in human breast cells.
AB  - In contrast to the classic view of static DNA double-strand breaks (DSBs) being
      repaired at the site of damage, we hypothesize that DSBs move and merge with each
      other over large distances (MUm). As X-ray dose increases, the probability of
      having DSB clusters increases as does the probability of misrepair and cell
      death. Experimental work characterizing the X-ray dose dependence of radiation
      induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is
      used here to validate a DSB clustering model. We then use the principles of the
      local effect model (LEM) to predict the yield of DSBs at the submicron level. Two
      mechanisms for DSB clustering, namely random coalescence of DSBs versus active
      movement of DSBs into repair domains are compared and tested. Simulations that
      best predicted both RIF dose dependence and cell survival after X-ray irradiation
      favored the repair domain hypothesis, suggesting the nucleus is divided into an
      array of regularly spaced repair domains of ~1.55 MUm sides. Applying the same
      approach to high-linear energy transfer (LET) ion tracks, we are able to predict
      experimental RIF/MUm along tracks with an overall relative error of 12%, for LET
      ranging between 30-350 keV/MUm and for three different ions. Finally, cell death
      was predicted by assuming an exponential dependence on the total number of DSBs
      and of all possible combinations of paired DSBs within each simulated RIF.
      Relative biological effectiveness (RBE) predictions for cell survival of MCF10A
      exposed to high-LET showed an LET dependence that matches previous experimental
      results for similar cell types. Overall, this work suggests that microdosimetric
      properties of ion tracks at the submicron level are sufficient to explain both
      RIF data and survival curves for any LET, similarly to the LEM assumption.
      Conversely, high-LET death mechanism does not have to infer linear-quadratic dose
      formalism as done in the LEM. In addition, the size of repair domains derived in
      our model are based on experimental RIF and are three times larger than the
      hypothetical LEM voxel used to fit survival curves. Our model is therefore an
      alternative to previous approaches that provides a testable biological mechanism
      (i.e., RIF). In addition, we propose that DSB pairing will help develop more
      accurate alternatives to the linear cancer risk model (LNT) currently used for
      regulating exposure to very low levels of ionizing radiation. 

PMID- 25076116
TI  - Independent validation of candidate genes identified after a whole genome
      screening on Mayak workers exposed to prolonged occupational radiation.
AB  - We evaluated gene expression in the peripheral blood of Mayak workers in
      relationship to occupational chronic exposure to identify permanent post-exposure
      signatures. The Mayak workers had experienced either a combined exposure to
      incorporated (239)Pu and external gamma rays (n = 82) or exposure to external
      gamma rays (n = 18). Fifty unexposed individuals served as controls. Peripheral
      blood was collected and then the RNA was isolated, converting it into cDNA and
      stored at -20 degrees C. In a previous study at stage I, we screened the mRNA and
      microRNA transcriptome using 40 of the 150 samples and identified 95 mRNAs and 45
      microRNAs. In stage II of this study, we now validated our 140 candidate genes
      using the qRT-PCR technique for the remaining 92 blood samples (18 samples were
      lost due to methodological reasons). We analyzed associations of normalized gene
      expression values in linear models separately for both exposure types (continuous
      and categorical scales) and adjusted for exposure age as well as stratified by
      gender. After further adjustment for confounders such as chronic non-cancer
      diseases or age at biosampling, mostly binary (on/off) dose-to-gene relationships
      were found for 15 mRNAs and 15 microRNAs, of which 8 mRNAs and 6 microRNAs
      remained significant after Bonferroni correction. Almost all of them were
      associated with plutonium incorporation and gender. Our study provides mRNA and
      microRNA gene expression changes dependent on the exposure type and gender, which
      occur and seem to persist after chronic radiation exposures supporting the
      concept of permanent post-exposure signatures. 

PMID- 25076118
TI  - Effects of Antibiotics on Bone and Soft-Tissue Healing Following Immediate Single
      Tooth Implant Placement Into Sites With Apical Pathology.
AB  - Overprescription of antibiotics can cause bacterial resistance problems, leading
      to life-threatening illnesses and public health crises. Clinicians often believe
      antibiotics can prevent dental implant failure and postoperative complications.
      In conjunction with implant surgery, antibiotics are therefore routinely
      prescribed for all cases. In this double-blind, randomized controlled trial, the
      effects of antibiotics on the clinical outcomes of immediate implant placement
      upon replacing a tooth with an apical pathology were examined to compare
      antibiotics (n = 10) and placebo (n = 10). In each subject, a tooth with a
      chronic apical lesion was extracted, thoroughly curetted, irrigated, and replaced
      with single implant with a screw-retained custom provisional abutment/crown.
      Postoperative pain/discomfort was measured at 1- and 4-week postsurgical follow
      up visits using visual analog scales. Facial alveolar bone and soft-tissue
      changes were measured using pre- and postoperative cone-beam computerized
      tomography and impressions. We found survival rates of 100% (antibiotics) and 78%
      (control). However, there was no statistical difference in means for any clinical
      outcome (t tests with Bonferroni adjustment for multiple testing), except for
      midfacial soft-tissue changes: 0.43 mm (SD, 0.76) in the antibiotics group and
      1.70 mm (SD, 1.06) in the placebo group (t15 = -2.89, P = .011). The average
      change of the midfacial alveolar plate was 0.62 mm (SD, 0.46) and 1.34 mm (SD,
      0.91) for the antibiotic and placebo groups, respectively, which did not
      significantly differ statistically. No significant correlation (Spearman
      correlation) existed between the changes in facial alveolar bone and the facial
      gingival margin. Antibiotics appear to have little effect on immediate implant
      treatment outcomes. 

PMID- 25076119
TI  - Design of the Study of Tranexamic Acid during Air Medical Prehospital Transport
      (STAAMP) Trial: Addressing the Knowledge Gaps.
AB  - Abstract Hemorrhage and coagulopathy remain major drivers of early preventable
      mortality in military and civilian trauma. The development of trauma-induced
      coagulopathy and hyperfibrinolysis is associated with poor outcomes. Interest in
      the use of tranexamic acid (TXA) in hemorrhaging patients as an antifibrinolytic
      agent has grown recently. Additionally, several reports describe immunomodulatory
      effects of TXA that may confer benefit independent of its antifibrinolytic
      actions. A large trial demonstrated a mortality benefit for early TXA
      administration in patients at risk for hemorrhage; however, questions remain
      about the applicability in developed trauma systems and the mechanism by which
      TXA reduces mortality. We describe here the rationale, design, and challenges of
      the Study of Tranexamic Acid during Air Medical Prehospital transport (STAAMP)
      trial. The primary objective is to determine the effect of prehospital TXA
      infusion during air medical transport on 30-day mortality in patients at risk of
      traumatic hemorrhage. This study is a multicenter, placebo-controlled, double
      blind, randomized clinical trial. The trial will enroll trauma patients with
      hypotension and tachycardia from 4 level I trauma center air medical transport
      programs. It includes a 2-phase intervention, with a prehospital and in-hospital
      phase to investigate multiple dosing regimens. The trial will also explore the
      effects of TXA on the coagulation and inflammatory response following injury. The
      trial will be conducted under exception for informed consent for emergency
      research and thus required an investigational new drug approval from the U.S.
      Food and Drug Administration as well as a community consultation process. It was
      designed to address several existing knowledge gaps and research priorities
      regarding TXA use in trauma.

PMID- 25076120
TI  - Epigenetic regulation of uterine biology by transcription factor KLF11 via
      posttranslational histone deacetylation of cytochrome p450 metabolic enzymes.
AB  - Endocrine regulation of uterine biology is critical for embryo receptivity and
      human reproduction. Uterine endometrium depends on extrinsic sex steroid input
      and hence likely has mechanisms that enable adaptation to hormonal variation.
      Emerging evidence suggests that sex steroid bioavailability in the endometrium is
      determined by adjusting their metabolic rate and fate via regulation of
      cytochrome (CYP) p450 enzymes. The CYP enzymes are targeted by ubiquitously
      expressed Sp/Kruppel-like (Sp/KLF) transcription factors. Specifically, KLF11 is
      highly expressed in reproductive tissues, regulates an array of
      endocrine/metabolic pathways via epigenetic histone-based mechanisms and, when
      aberrantly expressed, is associated with diabetes and reproductive tract
      diseases, such as leiomyoma and endometriosis. Using KLF11 as a model to
      investigate epigenetic regulation of endometrial first-pass metabolism, we
      evaluated the expression of a comprehensive array of metabolic enzymes in
      Ishikawa cells. KLF11 repressed most endometrial CYP enzymes. To characterize
      KLF11-recruited epigenetic regulatory mechanisms, we focused on the estrogen
      metabolizing enzyme CYP3A4. KLF11 expression declined in secretory phase
      endometrial epithelium associated with increased CYP3A4 expression. Additionally,
      KLF11 bound to CYP3A4 promoter GC elements and thereby repressed promoter,
      message, protein as well as enzymatic function. This repression was
      epigenetically mediated, because KLF11 colocalized with and recruited the
      corepressor SIN3A/histone deacetylase resulting in selective deacetylation of the
      CYP3A4 promoter. Repression was reversed by a mutation in KLF11 that abrogated
      cofactor recruitment and binding. This repression was also pharmacologically
      reversible with an histone deacetylase inhibitor. Pharmacological alteration of
      endometrial metabolism could have long-term translational implications on human
      reproduction and uterine disease.

PMID- 25076121
TI  - Androgen receptor inactivation resulted in acceleration in pubertal mammary gland
      growth, upregulation of ERalpha expression, and Wnt/beta-catenin signaling in
      female mice.
AB  - The androgen receptor (AR) is widely expressed in mammary cells of female mammals
      including humans and mice, indicating a possible role for AR-mediated androgen
      actions in breast development, function, and pathology, although the specific
      mechanisms remain unclear. To elucidate the mechanisms of androgen action in
      mammary gland physiology and development, we used AR-knockout (AR(Deltaex3)KO)
      female mice with a universally expressed, transcriptionally inactive AR protein
      harboring an in-frame deletion of its second zinc finger. Although in sexually
      mature wild-type (WT) and AR(ex3Delta)KO females, the mammary epithelial growth
      was fully extended to the edge of the fat pad, during puberty, AR(ex3Delta)KO
      females exhibit significantly accelerated mammary ductal growth and an increased
      number of terminal end buds compared with WT females. Accelerated AR(ex3Delta)KO
      female mammary growth was associated with significantly increased mammary
      epithelial ERalpha expression and activated Wnt/beta-catenin signaling as shown
      by increased Wnt4 expression and accumulation of nuclear beta-catenin. These
      findings are consistent with increased mammary estrogen exposure although ovarian
      estradiol content was unchanged compared with WT females. Furthermore, treatment
      with the potent pure androgen DHT markedly reduced ductal extension and terminal
      end bud numbers in WT but not in AR(Deltaex3)KO females, further supporting the
      concept that AR-mediated, androgen-induced suppression of murine mammary growth
      is a physiological characteristic of puberty. In summary, our findings reveal an
      inhibitory role of AR-mediated androgen actions in pubertal mammary gland
      development by reducing epithelial cell proliferation and could be mediated by
      regulation of Wnt/beta-catenin signaling. 

PMID- 25076122
TI  - Glucagon-like peptide (GCGL) is a novel potential TSH-releasing factor (TRF) in
      Chickens: I) Evidence for its potent and specific action on stimulating TSH mRNA
      expression and secretion in the pituitary.
AB  - Our recent study proposed that the novel glucagon-like peptide (GCGL), encoded by
      a glucagon-like gene identified in chickens and other lower vertebrates, is
      likely a hypophysiotropic factor in nonmammalian vertebrates. To test this
      hypothesis, in this study, we investigated the GCGL action on chicken
      pituitaries. The results showed that: 1) GCGL, but not TRH, potently and
      specifically stimulates TSH secretion in intact pituitaries incubated in vitro or
      in cultured pituitary cells monitored by Western blotting or a cell-based
      luciferase reporter assay; 2) GCGL (0.1nM-10nM) dose dependently induces the mRNA
      expression of TSHbeta but not 5 other hormone genes in cultured pituitary cells
      examined by quantitative real-time RT-PCR, an action likely mediated by
      intracellular adenylate cyclase/cAMP/protein kinase A and phospholipase
      C/inositol 1,4,5-trisphosphate/Ca(2+) signaling pathways coupled to GCGL receptor
      (GCGLR); 3) GCGLR mRNA is mainly localized in pituitary cephalic lobe
      demonstrated by in situ hybridization, where TSH-cells reside, further supporting
      a direct action of GCGL on thyrotrophs. The potent and specific action of GCGL on
      pituitary TSH expression and secretion, together with the partial accordance
      shown among the temporal expression profiles of GCGL in the hypothalamus and
      GCGLR and TSHbeta in the pituitary, provides the first collective evidence that
      hypothalamic GCGL is most likely to be a novel TSH-releasing factor functioning
      in chickens. The discovery of this novel potential TSH-releasing factor (GCGL) in
      a nonmammalian vertebrate species, ie, chickens, would facilitate our
      comprehensive understanding of the hypothalamic control of pituitary-thyroid axis
      across vertebrates.

PMID- 25076123
TI  - Microphynolides A and B, new spiro-gamma-lactone glycosides from Thymelaea
      microphylla.
AB  - Two new spiro-gamma-lactone glycosides named microphynolide A (1) and
      microphynolide B (2), together with twelve known compounds including five
      biflavonoids namely neochamaejasmin A, neochamaejasmin B, daphnodorin B,
      genkwanol A and stelleranol, one bis-coumarin daphnoretin, two lignans called
      pinoresinol and matairesinol, one flavonoid glucoside, tiliroside, a sinapyl
      alcohol glucoside, syringin, and two phytosterols, beta-sitosterol and beta
      sitosterol-3-O-glucoside, were isolated from ethyl acetate extracts of the aerial
      parts and roots of the plant Thymelaea microphylla Coss. and Dur. All the
      isolated compounds were characterised by using spectroscopic methods and
      comparison with the literature data. 

PMID- 25076124
TI  - Laser direct synthesis and patterning of silver nano/microstructures on a polymer
      substrate.
AB  - This study presents a novel approach for the rapid fabrication of conductive
      nano/microscale metal structures on flexible polymer substrate (polyimide).
      Silver film is simultaneously synthesized and patterned on the polyimide
      substrate using an advanced continuous wave (CW) laser direct writing technology
      and a transparent, particle-free reactive silver ion ink. The location and shape
      of the resulting silver patterns are written by a laser beam from a digitally
      controlled micromirror array device. The silver patterns fabricated by this laser
      direct synthesis and patterning (LDSP) process exhibit the remarkably low
      electrical resistivity of 2.1 MUOmega cm, which is compatible to the electrical
      resistivity of bulk silver. This novel LDSP process requires no vacuum chamber or
      photomasks, and the steps needed for preparation of the modified reactive silver
      ink are simple and straightforward. There is none of the complexity and
      instability associated with the synthesis of the nanoparticles that are
      encountered for the conventional laser direct writing technology which involves
      nanoparticle sintering process. This LDSP technology is an advanced method of
      nano/microscale selective metal patterning on flexible substrates that is fast
      and environmentally benign and shows potential as a feasible process for the roll
      to-roll manufacturing of large area flexible electronic devices. 

PMID- 25076125
TI  - Identification of a novel luminal molecular subtype of breast cancer.
AB  - The molecular classification of human breast tumors has afforded insights into
      subtype specific biological processes, patient prognosis and response to
      therapies. However, using current methods roughly one quarter of breast tumors
      cannot be classified into one or another molecular subtype. To explore the
      possibility that the unclassifiable samples might comprise one or more novel
      subtypes we employed a collection of publically available breast tumor datasets
      with accompanying clinical information to assemble 1,593 transcript profiles: 25%
      of these samples could not be assigned to one of the current molecular subtypes
      of breast cancer. All of the unclassifiable samples could be grouped into a new
      molecular subtype, which we termed "luminal-like". We also identified the luminal
      like subtype in an independent collection of tumor samples (NKI295). We found
      that patients harboring tumors of the luminal-like subtype have a better
      prognosis than those with basal-like breast cancer, a similar prognosis to those
      with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients
      with luminal A or normal-like breast tumors. Our findings suggest the occurrence
      of another molecular subtype of breast cancer that accounts for the vast majority
      of previously unclassifiable breast tumors. 

PMID- 25076127
TI  - Synthesis and accumulation of aromatic aldehydes in an engineered strain of
      Escherichia coli.
AB  - Aromatic aldehydes are useful in numerous applications, especially as flavors,
      fragrances, and pharmaceutical precursors. However, microbial synthesis of
      aldehydes is hindered by rapid, endogenous, and redundant conversion of aldehydes
      to their corresponding alcohols. We report the construction of an Escherichia
      coli K-12 MG1655 strain with reduced aromatic aldehyde reduction (RARE) that
      serves as a platform for aromatic aldehyde biosynthesis. Six genes with reported
      activity on the model substrate benzaldehyde were rationally targeted for
      deletion: three genes that encode aldo-keto reductases and three genes that
      encode alcohol dehydrogenases. Upon expression of a recombinant carboxylic acid
      reductase in the RARE strain and addition of benzoate during growth, benzaldehyde
      remained in the culture after 24 h, with less than 12% conversion of benzaldehyde
      to benzyl alcohol. Although individual overexpression results demonstrated that
      all six genes could contribute to benzaldehyde reduction in vivo, additional
      experiments featuring subset deletion strains revealed that two of the gene
      deletions were dispensable under the conditions tested. The engineered strain was
      next investigated for the production of vanillin from vanillate and succeeded in
      preventing formation of the byproduct vanillyl alcohol. A pathway for the
      biosynthesis of vanillin directly from glucose was introduced and resulted in a
      55-fold improvement in vanillin titer when using the RARE strain versus the wild
      type strain. Finally, synthesis of the chiral pharmaceutical intermediate L
      phenylacetylcarbinol (L-PAC) was demonstrated from benzaldehyde and glucose upon
      expression of a recombinant mutant pyruvate decarboxylase in the RARE strain.
      Beyond allowing accumulation of aromatic aldehydes as end products in E. coli,
      the RARE strain expands the classes of chemicals that can be produced microbially
      via aldehyde intermediates.

PMID- 25076126
TI  - Dynamics of brush border remodeling induced by enteropathogenic E. coli.
AB  - Enteropathogenic Escherichia coli (EPEC) induces dramatic remodeling of
      enterocyte brush borders, a process that includes microvillar effacement and
      actin pedestal formation. Although the Arp2/3 complex is involved in formation of
      a branched actin network within pedestals, the fate of parallel actin bundles in
      microvilli during infection remains unclear. Here, we find that in polarized
      intestinal epithelial cells, EPEC stimulates long-range microvillar dynamics,
      pulling protrusions toward sites of bacterial attachment in a process mediated by
      the adhesion molecule protocadherin-24. Additionally, retraction of the EPEC
      bundle forming pilus stimulates directed elongation of nearby microvilli. These
      processes lead to coalescence of microvilli and incorporation of the underlying
      parallel actin bundles into pedestals. Furthermore, stabilization of microvillar
      actin bundles delays pedestal formation. Together, these results suggest a model
      where EPEC takes advantage of pre-existing actin filaments in microvillar core
      bundles to facilitate pedestal formation. 

PMID- 25076129
TI  - The role of integrative taxonomy in the conservation management of cryptic
      species: the taxonomic status of endangered earless dragons (Agamidae:
      Tympanocryptis) in the grasslands of Queensland, Australia.
AB  - Molecular phylogenetics is increasingly highlighting the prevalence of cryptic
      species, where morphologically similar organisms have long independent
      evolutionary histories. When such cryptic species are known to be declining in
      numbers and are at risk of extinction due to a range of threatening processes,
      the disjunction between molecular systematics research and conservation policy
      becomes a significant problem. We investigate the taxonomic status of
      Tympanocryptis populations in Queensland, which have previously been assigned to
      T. tetraporophora, using three species delimitation approaches. The taxonomic
      uncertainties in this species-group are of particular importance in the Darling
      Downs Earless Dragon (T. cf. tetraporophora), which is ranked as an endangered
      'species' of high priority for conservation by the Queensland Department of
      Environment and Heritage Protection. We undertook a morphological study,
      integrated with a comprehensive genetic study and species delimitation analyses,
      to investigate the species status of populations in the region. Phylogenetic
      analyses of two gene regions (mtDNA: ND2; nuclear: RAG1) revealed high levels of
      genetic divergence between populations, indicating isolation over long
      evolutionary time frames, and strongly supporting two independent evolutionary
      lineages in southeastern Queensland, from the Darling Downs, and a third in the
      Gulf Region of northern Queensland. Of the three species delimitation protocols
      used, we found integrative taxonomy the most applicable to this cryptic species
      complex. Our study demonstrates the utility of integrative taxonomy as a species
      delimitation approach in cryptic complexes of species with conservation
      significance, where limited numbers of specimens are available. 

PMID- 25076128
TI  - In a safety net population HPV4 vaccine adherence worsens as BMI increases.
AB  - OBJECTIVES: Obesity adversely inhibits antibody response to vaccination. Three
      doses of HPV4 may or may not provide adequate long term protection against HPV
      16/18 in obese females. The aim of this study was to determine whether adherence
      to HPV4 vaccination in a safety net population was reduced with increasing body
      mass index (BMI). METHODS: We designed a historical prospective study evaluating
      the number and dates of HPV4 dosing that occurred from July 1, 2006 through
      October 1, 2009 by the demographic characteristics of the 10-26 year old
      recipient females. The defined dosing intervals were adapted from the literature
      and obesity categories were defined by the WHO. RESULTS: 1240 females with BMI
      measurements received at least one dose of HPV4; 38% were obese (class I, II and
      III) and 25% were overweight. Females with normal BMI received on-time triplet
      dosing significantly more often than did the obese class II and III females (30%
      vs. 18%, p<0.001). Obese class II/III females have a significant 45% less chance
      of completing the on-time triplet HPV4 series than normal women (OR = 0.55, 95%
      CI: 0.37, 0.83). Pregnancy history has a significant influence on BMI and HPV4
      dosing compliance in this safety net population where 71% had been gravid.
      Hispanic females were less likely to complete HPV4 dosing regardless of BMI (aOR
      = 0.39, 95% CI: 0.16, 0.95). CONCLUSIONS: Obesity, as well as gravidity and
      Hispanic race, are risk factors for lack of HPV4 vaccine adherence among young
      females in a safety net population.

PMID- 25076131
TI  - Silver-catalyzed tandem hydroamination/hydroarylation of 1-(2-allylamino)phenyl-4
      hydroxy-but-2-yn-1-ones to 1'-allylspiro[indene-1,2'-indolin]-3'-ones.
AB  - An efficient silver triflate-catalyzed tandem hydroamination/hydroarylation
      cascade generating 1'-allylspiro[indene-1,2'-indolin]-3'-ones from 1-(2
      allylamino)phenyl-4-hydroxy-but-2-yn-1-ones is described. The reaction conditions
      are mild and general in scope and proceed to highly functionalized spiro-targets
      in high yield. This novel class of molecule possesses both the privileged indene
      and indolin-3-one scaffold, which may lead to possible pharmacological
      applications. 

PMID- 25076133
TI  - Photoelectron spectroscopy of CoC2H2(-) and density functional study of Co(n)C2H2
      (n = 1-3) anion and neutral clusters.
AB  - The anionic and neutral ConC2H2 (n = 1-3) clusters were investigated using anion
      photoelectron spectroscopy and density functional calculations. The adiabatic
      detachment energies and vertical detachment energies of ConC2H2(-) (n = 1-3) were
      determined. Our results show that the most stable geometries of anionic ConC2H2(
      ) (n = 1-2) and neutral ConC2H2 (n = 1-3) are composed of ConC2H clusters
      adsorbing a hydrogen atom on the top or bridge sites of Con, whereas Co3C2H2(-)
      consists of a five-member ring of Co3C2 carbide adsorbing two hydrogen atoms on
      two bridge sites of Co3. The reaction mechanisms show that the inserted isomer
      HCoC2H can convert into the vinylidene complex Co?C?CH2 via a side-on isomer M
      eta(2)-(C2H2). 

PMID- 25076130
TI  - St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic
      therapy induces metastatic melanoma cell death.
AB  - Hypericin, an extract from St John's Wort (Hypericum perforatum L.), is a
      promising photosensitizer in the context of clinical photodynamic therapy due to
      its excellent photosensitizing properties and tumoritropic characteristics.
      Hypericin-PDT induced cytotoxicity elicits tumor cell death by various mechanisms
      including apoptosis, necrosis and autophagy-related cell death. However, limited
      reports on the efficacy of this photomedicine for the treatment of melanoma have
      been published. Melanoma is a highly aggressive tumor due to its metastasizing
      potential and resistance to conventional cancer therapies. The aim of this study
      was to investigate the response mechanisms of melanoma cells to hypericin-PDT in
      an in vitro tissue culture model. Hypericin was taken up by all melanoma cells
      and partially co-localized to the endoplasmic reticulum, mitochondria, lysosomes
      and melanosomes, but not the nucleus. Light activation of hypericin induced a
      rapid, extensive modification of the tubular mitochondrial network into a beaded
      appearance, loss of structural details of the endoplasmic reticulum and
      concomitant loss of hypericin co-localization. Surprisingly the opposite was
      found for lysosomal-related organelles, suggesting that the melanoma cells may be
      using these intracellular organelles for hypericin-PDT resistance. In line with
      this speculation we found an increase in cellular granularity, suggesting an
      increase in pigmentation levels in response to hypericin-PDT. Pigmentation in
      melanoma is related to a melanocyte-specific organelle, the melanosome, which has
      recently been implicated in drug trapping, chemotherapy and hypericin-PDT
      resistance. However, hypericin-PDT was effective in killing both unpigmented
      (A375 and 501mel) and pigmented (UCT Mel-1) melanoma cells by specific mechanisms
      involving the externalization of phosphatidylserines, cell shrinkage and loss of
      cell membrane integrity. In addition, this treatment resulted in extrinsic (A375)
      and intrinsic (UCT Mel-1) caspase-dependent apoptotic modes of cell death, as
      well as a caspase-independent apoptotic mode that did not involve apoptosis
      inducing factor (501 mel). Further research is needed to shed more light on these
      mechanisms. 

PMID- 25076136
TI  - The vocal repertoire of the African Penguin (Spheniscus demersus): structure and
      function of calls.
AB  - The African Penguin (Spheniscus demersus) is a highly social and vocal seabird.
      However, currently available descriptions of the vocal repertoire of African
      Penguin are mostly limited to basic descriptions of calls. Here we provide, for
      the first time, a detailed description of the vocal behaviour of this species by
      collecting audio and video recordings from a large captive colony. We combine
      visual examinations of spectrograms with spectral and temporal acoustic analyses
      to determine vocal categories. Moreover, we used a principal component analysis,
      followed by signal classification with a discriminant function analysis, for
      statistical validation of the vocalisation types. In addition, we identified the
      behavioural contexts in which calls were uttered. The results show that four
      basic vocalisations can be found in the vocal repertoire of adult African
      Penguin, namely a contact call emitted by isolated birds, an agonistic call used
      in aggressive interactions, an ecstatic display song uttered by single birds, and
      a mutual display song vocalised by pairs, at their nests. Moreover, we identified
      two distinct vocalisations interpreted as begging calls by nesting chicks
      (begging peep) and unweaned juveniles (begging moan). Finally, we discussed the
      importance of specific acoustic parameters in classifying calls and the possible
      use of the source-filter theory of vocal production to study penguin
      vocalisations. 

PMID- 25076134
TI  - Structural basis for the recognition in an idiotype-anti-idiotype antibody
      complex related to celiac disease.
AB  - Anti-idiotype antibodies have potential therapeutic applications in many fields,
      including autoimmune diseases. Herein we report the isolation and
      characterization of AIM2, an anti-idiotype antibody elicited in a mouse model
      upon expression of the celiac disease-specific autoantibody MB2.8 (directed
      against the main disease autoantigen type 2 transglutaminase, TG2). To
      characterize the interaction between the two antibodies, a 3D model of the MB2.8
      AIM2 complex has been obtained by molecular docking. Analysis and selection of
      the different obtained docking solutions was based on the conservation within
      them of the inter-residue contacts. The selected model is very well
      representative of the different solutions found and its stability is confirmed by
      molecular dynamics simulations. Furthermore, the binding mode it adopts is very
      similar to that observed in most of the experimental structures available for
      idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is
      directed against the MB2.8 CDR region, especially on its variable light chain.
      This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8
      TG2 complex incompatible, thus explaining the experimentally observed inhibitory
      effect on the MB2.8 binding to TG2. 

PMID- 25076135
TI  - Nuclease-assisted suppression of human DNA background in sepsis.
AB  - Sepsis is a severe medical condition characterized by a systemic inflammatory
      response of the body caused by pathogenic microorganisms in the bloodstream.
      Blood or plasma is typically used for diagnosis, both containing large amount of
      human DNA, greatly exceeding the DNA of microbial origin. In order to enrich
      bacterial DNA, we applied the C0t effect to reduce human DNA background: a model
      system was set up with human and Escherichia coli (E. coli) DNA to mimic the
      conditions of bloodstream infections; and this system was adapted to plasma and
      blood samples from septic patients. As a consequence of the C0t effect, abundant
      DNA hybridizes faster than rare DNA. Following denaturation and re-hybridization,
      the amount of abundant DNA can be decreased with the application of double strand
      specific nucleases, leaving the non-hybridized rare DNA intact. Our experiments
      show that human DNA concentration can be reduced approximately 100,000-fold
      without affecting the E. coli DNA concentration in a model system with similarly
      sized amplicons. With clinical samples, the human DNA background was decreased
      100-fold, as bacterial genomes are approximately 1,000-fold smaller compared to
      the human genome. According to our results, background suppression can be a
      valuable tool to enrich rare DNA in clinical samples where a high amount of
      background DNA can be found. 

PMID- 25076137
TI  - Unexpected attraction of polarotactic water-leaving insects to matt black car
      surfaces: mattness of paintwork cannot eliminate the polarized light pollution of
      black cars.
AB  - The horizontally polarizing surface parts of shiny black cars (the reflection
      polarization characteristics of which are similar to those of water surfaces)
      attract water-leaving polarotactic insects. Thus, shiny black cars are typical
      sources of polarized light pollution endangering water-leaving insects. A new
      fashion fad is to make car-bodies matt black or grey. Since rough (matt) surfaces
      depolarize the reflected light, one of the ways of reducing polarized light
      pollution is to make matt the concerned surface. Consequently, matt black/grey
      cars may not induce polarized light pollution, which would be an advantageous
      feature for environmental protection. To test this idea, we performed field
      experiments with horizontal shiny and matt black car-body surfaces laid on the
      ground. Using imaging polarimetry, in multiple-choice field experiments we
      investigated the attractiveness of these test surfaces to various water-leaving
      polarotactic insects and obtained the following results: (i) The attractiveness
      of black car-bodies to polarotactic insects depends in complex manner on the
      surface roughness (shiny, matt) and species (mayflies, dolichopodids, tabanids).
      (ii) Non-expectedly, the matt dark grey car finish is much more attractive to
      mayflies (being endangered and protected in many countries) than matt black
      finish. (iii) The polarized light pollution of shiny black cars usually cannot be
      reduced with the use of matt painting. On the basis of these, our two novel
      findings are that (a) matt car-paints are highly polarization reflecting, and (b)
      these matt paints are not suitable to repel polarotactic insects. Hence, the
      recent technology used to make matt the car-bodies cannot eliminate or even can
      enhance the attractiveness of black/grey cars to water-leaving insects. Thus,
      changing shiny black car painting to matt one is a disadvantageous fashion fad
      concerning the reduction of polarized light pollution of black vehicles. 

PMID- 25076138
TI  - Factors influencing crystal growth rates from undercooled liquids of
      pharmaceutical compounds.
AB  - Amorphous forms of drugs are increasingly being used to deliver poorly water
      soluble compounds. Therefore, understanding the magnitude and origin of
      differences in crystallization kinetics is highly important. The goal of this
      study was to better understand the factors that influence crystal growth rates
      from pharmaceutically relevant undercooled liquids and to evaluate the range of
      growth rates observed. The crystal growth rates of 31 drugs were determined using
      an optical microscope in the temperature region between the glass transition
      temperature (Tg) and the melting temperature (Tm). Thermodynamic parameters such
      as Tm, melting enthalpy, and Tg were determined using a differential scanning
      calorimeter (DSC). Selected viscosity values for the undercooled liquid were
      taken from the literature. The growth rates of the different compounds were found
      to be very different from each other with a variation of about 5 orders of
      magnitude between the fastest growing compounds and the slowest growing
      compounds. A comparison of the physicochemical properties showed that compounds
      that had fast crystal growth rates had smaller molecular weights, higher melting
      temperatures, lower melt entropies, lower melt viscosities, and higher crystal
      densities. Variations in the growth rates of the compounds could be rationalized
      to a large extent by considering the thermodynamic driving force for
      crystallization, the viscosity, and the entropy difference between the melt and
      undercooled liquid. This study therefore provides important insight into factors
      that may compromise the stability of amorphous pharmaceuticals. 

PMID- 25076139
TI  - Oxidised cellulose powder for haemostasis following sinus surgery: a pilot
      randomised trial.
AB  - BACKGROUND: Haemorrhage is the most common major complication of endoscopic sinus
      surgery. Post-operative absorbable or non-absorbable nasal packing can cause pain
      and blockage. Haemostatic powders or gels may prevent this problem. However, when
      based on factors in the clotting cascade, they induce an inflammatory reaction
      and can cause post-operative synechiae. Oxidised cellulose powder produces
      haemostasis without inducing synechiae formation, but has not been trialled for
      sinus surgery. METHOD: A randomised clinical trial was performed to compare
      cellulose powder to non-absorbable packing following sinus surgery. Participants
      were 50 consecutive patients undergoing sinus surgery, 47 of whom completed the
      study. The main outcome measures were post-operative bleeding, pain scores and
      synechiae formation. RESULTS: Cellulose powder was effective at stopping
      bleeding, and was associated with less pain than nasal packing, with no evidence
      of increased synechiae formation. CONCLUSION: Cellulose powder appears to be a
      good haemostatic agent following sinus surgery. A larger trial would allow more
      accurate quantification of its effectiveness.

PMID- 25076140
TI  - Electrochemical reduction of Bronsted acids by glassy carbon in acetonitrile
      implications for electrocatalytic hydrogen evolution.
AB  - Molecular catalysts for electrochemically driven hydrogen evolution are often
      studied in acetonitrile with glassy carbon working electrodes and Bronsted acids.
      Surprisingly, little information is available regarding the potentials at which
      acids are directly reduced on glassy carbon. This work examines acid
      electroreduction in acetonitrile on glassy carbon electrodes by cyclic
      voltammetry. Reduction potentials, spanning a range exceeding 2 V, were found for
      20 acids. The addition of 100 mM water was not found to shift the reduction
      potential of any acid studied, although current enhancement was observed for some
      acids. The data reported provides a guide for selecting acids to use in
      electrocatalysis experiments such that direct electrode reduction is avoided. 

PMID- 25076141
TI  - Polyphenols with anti-proliferative activities from Penthorum chinense Pursh.
AB  - Two new polyphenols, penthorumin C (1) and 2,6-dihydroxyacetophenone-4-O- [4',6'
      (S)-hexahydroxydiphenoyl]-beta-D-glucose (2), along with four known polyphenolic
      acids, pinocembrin-7-O-[4",6"-hexahydroxydiphenoyl]-beta-D-glucose(3),
      pinocembrin-7-O-[3"-O- galloyl- 4",6"-hexahydroxydiphenoyl]-beta-D-glucose (4),
      thonningianin A (5), and thonningianin B (6) were isolated from Penthourm
      chinense. All compounds were evaluated for their anti-proliferative activity in
      HSC-T6 cells, and 2 and 5 showed significant activity, with IC50 values of 12.7
      and 19.2 MUM, respectively.

PMID- 25076142
TI  - Bifunctionalized allenes. Part XV. Synthesis of 2,5-dihydro-1,2-oxaphospholes by
      electrophilic cyclization reaction of phosphorylated alpha-hydroxyallenes.
AB  - This paper discusses a reaction of phosphorylated alpha-hydroxyallenes with
      protected or unprotected hydroxy groups involving 5-endo-trig cyclizations.
      Various electrophilic reagents such as sulfuryl chloride, bromine,
      benzenesulfenyl and benzeneselenenyl chlorides have been applied. The paper
      describes the reaction of 1-hydroxyalkyl-1,2-dienephosphonates with electrophiles
      that produces 2-methoxy-2-oxo-2,5-dihydro-1,2-oxaphospholes due to the
      participation of the phosphonate neighbouring group in the cyclization. On the
      other hand, (1E)-alk-1-en-1-yl phosphine oxides were prepared as mixtures with
      2,5-dihydro-1,2-oxaphosphol-2-ium halides in a ratio of about 1:2 by chemo-,
      regio, and stereoselective electrophilic addition to the C(2)-C(3)-double bond in
      the allene moiety and subsequent concurrent attack of the external (halide anion)
      and internal (phosphine oxide group) nucleophiles. The paper proposes a possible
      mechanism that involves cyclization and additional reactions of the
      phosphorylated alpha-hydroxyallenes.

PMID- 25076143
TI  - Activity of antifungal organobismuth(III) compounds derived from alkyl aryl
      ketones against S. cerevisiae: comparison with a heterocyclic bismuth scaffold
      consisting of a diphenyl sulfone.
AB  - A series of hypervalent organobismuth(III) compounds derived from alkyl aryl
      ketones [XBi(5-R'C6H3-2-COR)(Ar)] was synthesized to investigate the effect of
      the compounds' structural features on their antifungal activity against the yeast
      Saccharomyces cerevisiae. In contrast to bismuth heterocycles [XBi(5-RC6H3-2
      SO2C6H4-1'-)] derived from diphenyl sulfones, a systematic quantitative structure
      activity relationship study was possible. The activity depended on the Ar group
      and increased for heavier X atoms, whereas lengthening the alkyl chain (R) or
      introducing a substituent (R') reduced the activity. IBi(C6H4-2-COCH3)(4-FC6H4)
      was the most active. Its activity was superior to that of the related acyclic
      analogues ClBi[C6H4-2-CH2N(CH3)2](Ar) and ClBi(C6H4-2-SO2 tert-Bu)(Ar) and also
      comparable to that of heterocyclic ClBi(C6H4-2-SO2C6H4-1'-), which was the most
      active compound in our previous studies. Density function theory calculations
      suggested that hypervalent bismuthanes undergo nucleophilic addition with a
      biomolecule at the bismuth atom to give an intermediate ate complex. For higher
      antifungal activity, adjusting the lipophilicity-hydrophilicity balance, modeling
      the three-dimensional molecular structure around the bismuth atom, and
      stabilizing the ate complex appear to be more important than tuning the Lewis
      acidity at the bismuth atom. 

PMID- 25076144
TI  - Photobleaching kinetics and time-integrated emission of fluorescent probes in
      cellular membranes.
AB  - Since the pioneering work of Hirschfeld, it is known that time-integrated
      emission (TiEm) of a fluorophore is independent of fluorescence quantum yield and
      illumination intensity. Practical implementation of this important result for
      determining exact probe distribution in living cells is often hampered by the
      presence of autofluorescence. Using kinetic modelling of photobleaching combined
      with pixel-wise bleach rate fitting of decay models with an updated plugin to the
      ImageJ program, it is shown that the TiEm of a fluorophore in living cells can be
      determined exactly from the product of bleaching amplitude and time constant.
      This applies to mono-exponential bleaching from the first excited singlet and/or
      triplet state and to multi-exponential combinations of such processes. The TiEm
      can be used to correct for illumination shading and background autofluorescence
      without the need for fluorescent test layers or separate imaging of non-stained
      cells. We apply the method to simulated images and to images of cells, whose
      membranes were labelled with fluorescent sterols and sphingolipids. Our bleaching
      model can be extended to include a probability density function (PDF) of
      intrinsic bleach rate constants with a memory kernel. This approach results in a
      time-dependent bleach rate coefficient and is exemplified for fluorescent sterols
      in restricted intracellular environments, like lipid droplets. We show that for
      small deviations from the classical exponential bleaching, the TiEm of decay
      functions with rate coefficients remains largely independent of fluorescence
      lifetime and illumination, and thereby represents a faithful measure of probe
      distribution. 

PMID- 25076145
TI  - Mixed culture fermentation and media optimization by response surface model:
      Streptomyces and Brachybacterium species in bioflocculant production.
AB  - The biofloculant production potential of a consortium of Streptomyces and
      Brachybacterium species were evaluated. Optimum bioflocculant yields (g/L) and
      flocculation activities (%) were observed for the following preferred nutritional
      sources: glucose (56%; 2.78 +/- 0.15 g/L), (NH4)2NO3 (53%; 2.81 +/- 0.37 g/L) and
      CaSO4 . H2O (47%; 2.19 +/- 0.13 g/L). A Plackett-Burman design revealed the
      critical fermentation media components. The concentrations of these components
      were optimized [glucose; 16.0, (NH4)2NO3; 0.5 and CaSO4 . H2O; 1.2 (g/L)] through
      a central composite design with optimum bioflocculant yield of 3.02 g/L and
      flocculation activity of 63.7%. The regression coefficient (R(2) = 0.6569)
      indicates a weak estimation of the model's adequacy and a high lack-of-fit value
      (34.1%). Lack of synergy in the consortium may have been responsible for the
      model inadequacy observed. FTIR spectrometry showed the bioflocculant to be a
      heteropolysaccharide, while SEM imaging revealed an amorphous loosely arranged
      fluffy structure with interstial spacing of less than 1 um.

PMID- 25076146
TI  - Effects of tatariside G isolated from Fagopyrum tataricum roots on apoptosis in
      human cervical cancer HeLa cells.
AB  - Cervical cancer is the second most common female carcinoma. Current therapies are
      often unsatisfactory, especially for advanced stage patients. The aim of this
      study was to explore the effects of tatariside G (TG) on apoptosis in human
      cervical cancer HeLa cells and the possible mechanism of action involved. An MTT
      assay was employed to evaluate cell viability. Hoechst 33258 staining and flow
      cytometry (FCM) assays were used to detect cell apoptosis. The protein expression
      of phosphorylated JNK, P38, ERK and Akt and cleaved caspase-3 and caspase-9 was
      evaluated by western blot analysis. Additionally, the mRNA expression of caspase
      3 and caspase-9 was measured by fluorescent quantitative reverse transcription
      PCR (FQ-RT-PCR). TG notably inhibited cell viability, enhanced the percentage of
      apoptotic cells, facilitated the phosphorylation of p38 MAPK and JNK proteins and
      caspase-3 and caspase-9 cracking, downregulated the phosphorylation level of Akt,
      and increased the loss of MMP and the mRNA expression of caspase-3 and caspase-9.
      TG-induced apoptosis is associated with activation of the mitochondrial death
      pathway. TG may be an effective candidate for chemotherapy against cervical
      cancer. 

PMID- 25076147
TI  - Reflections on the origins of the International Society for Environmental
      Epidemiology after its first 25 years.

PMID- 25076148
TI  - Commentary: much ado about interactions.

PMID- 25076149
TI  - Rejoinder: interacting on interactions.

PMID- 25076150
TI  - Commentary: regression discontinuity design: let's give it a try to evaluate
      medical and public health interventions.

PMID- 25076151
TI  - Intraclass correlation coefficient for grouped data.

PMID- 25076152
TI  - Quantitative falsification of instrumental variables assumption using balance
      measures.

PMID- 25076153
TI  - Optimal matching ratios in drug safety surveillance.

PMID- 25076154
TI  - Validating assisted reproductive technology self-report.

PMID- 25076155
TI  - Bounds for pure direct effect.

PMID- 25076156
TI  - Air pollution and life expectancy.

PMID- 25076157
TI  - Long-term mobile phone use and acoustic neuroma.

PMID- 25076158
TI  - The authors respond.

PMID- 25076159
TI  - 90Y-ibritumomab tiuxetan therapy in allogeneic transplantation in B-cell lymphoma
      with extensive marrow involvement and chronic lymphocytic leukemia: utility of
      pretransplantation biodistribution.
AB  - BACKGROUND: Biodistribution data to date using In-ibritumomab tiuxetan have been
      initially obtained in patients with less than 25% lymphomatous bone marrow
      involvement and adequate hematopoietic synthetic function. In this article we
      present the results of an analysis of the biodistribution data obtained from a
      cohort of patients with extensive bone marrow involvement, baseline cytopenias,
      and chronic lymphocytic leukemia (CLL). MATERIALS AND METHODS: Thirty-nine
      patients with a diagnosis of B-cell lymphoma or CLL expressing the CD20 antigen,
      who had failed at least one prior regimen, and had evidence of persistent disease
      were included in this analysis; however, only 38 of them completed the treatment.
      Semiquantitative analysis of the biodistribution was performed using regions of
      interest over the liver, lungs, kidneys, spleen, and sacrum. The observed
      interpatient variability including higher liver uptake in four patients is
      discussed. RESULTS: No severe solid organ toxicity was observed at the maximum
      administered activity of 1184 MBq (32 mCi) Y-ibritumomab tiuxetan. After
      accounting for differences in marrow involvement, patients with CLL exhibit
      comparable biodistributions to those with B-NHL. We found that the estimated
      sacral marrow uptake on 48 h images in patients with bone marrow involvement may
      be an indicator of bone marrow involvement. There was no correlation between
      tumor visualization and response to treatment. CONCLUSION: These data suggest
      that the imaging step is not critical when the administered activity is below
      1184 MBq (32 mCi). However, our analysis confirms that the semiquantitative
      imaging data can be used to identify patients at risk for liver toxicity when
      higher doses of Y-ibritumomab tiuxetan are used. Patients with CLL can have
      excellent targeting of disease by In-ibritumomab tiuxetan, indicating potential
      efficacy in this patient population.

PMID- 25076160
TI  - Scintigraphic assessments of the reparative process in osteonecrosis of the
      femoral head using SPECT/CT with 99mTc hydroxymethylene diphosphonate.
AB  - OBJECTIVE: The aim of the study was to assess the degree and location of the
      reparative process in early osteonecrosis of the femoral head on the basis of
      single-photon emission computed tomography/computed tomography (SPECT/CT) with
      technetium-99m hydroxymethylene diphosphonate. MATERIALS AND METHODS: This study
      was approved by the institutional review board. We retrospectively evaluated
      SPECT/CT scans of 23 consecutive hips. On the basis of the classification system
      used, 12 hips were classified as stage 1 (no radiographic abnormality), six hips
      as stage 2 (demarcating sclerosis without femoral head collapse), and five hips
      as stage 3A (<3 mm femoral head collapse). In each femoral head, the area with
      the maximum uptake count was defined as the region of maximum uptake. The degree
      of maximum uptake was assessed by the count ratio, which was defined as the
      maximum count within the femoral head divided by the mean uptake count of the
      cross-sectional region of the ipsilateral femur at the level of the distal end of
      the lesser trochanter. RESULTS: In stage 1, the maximum uptake count tended to
      occur in the anterior region of the femoral head. Meanwhile, in both stage 2 and
      stage 3A, the maximum uptake count was more likely to be observed in the lateral
      region. The mean count ratio of stage 2 was significantly higher than that of
      stage 1. CONCLUSION: We speculate that osteoblastic activity in the precollapsed
      stage may gradually increase around the necrotic lesion, with a tendency to
      advance toward the lateral region of the femoral head.

PMID- 25076161
TI  - Rifaximin suppresses background intestinal 18F-FDG uptake on PET/CT scans.
AB  - BACKGROUND: Identification of cancer or inflammatory bowel disease in the
      intestinal tract by PET/computed tomography (CT) imaging can be hampered by
      physiological uptake of F-fluorodeoxyglucose (F-FDG) in the normal colon.
      Previous work has localized this F-FDG uptake to the intestinal lumen,
      predominantly occupied by bacteria. We sought to determine whether pretreatment
      with an antibiotic could reduce F-FDG uptake in the healthy colon. PATIENTS AND
      METHODS: Thirty patients undergoing restaging PET/CT for nongastrointestinal
      lymphoma were randomly selected to receive rifaximin 550 mg twice daily for 2
      days before their scan (post-rifaximin). Their PET/CT images were compared with
      those from their prior study (pre-rifaximin). Cecal maximum standard uptake value
      (SUVmax) and overall colonic F-FDG uptake were compared between scans. All PET/CT
      images were blindly scored by a radiologist. The same comparison of sequential
      scans was also undertaken in 30 patients who did not receive antibiotics.
      RESULTS: Thirty post-rifaximin scans were compared with 30 pre-rifaximin scans in
      the same patients. SUVmax in the cecum was significantly lower in the patient's
      post-rifaximin scans than in their pre-rifaximin scans (P=0.002). The percentage
      of scans with greater than grade 1 colonic F-FDG uptake was significantly lower
      in the post-rifaximin scans than in the pre-rifaximin scans (P<0.05). In
      contrast, there was no significant difference in the paired sequential scans from
      control patients, nor a reduction in the percentage of scans with greater than
      grade 1 colonic F-FDG uptake. CONCLUSION: This pilot study shows that treatment
      with rifaximin for 2 days before PET/CT scanning can significantly reduce
      physiological F-FDG uptake in the normal colonic lumen.

PMID- 25076162
TI  - [Transsternal transpericardial closure of bronchopleural fistula after
      pneumonectomy].

PMID- 25076163
TI  - [Venous Access Port Implantation is an Ideal Teaching Operation - An Analysis of
      1423 Cases].
AB  - AIM: The aim of this study was the analysis of total, early and late
      complications following venous access port implantation between 1998 and 2008 at
      the Department of Surgery of the University of Rostock, Germany. A comparison
      between different implantation techniques addressing success rate, complication
      rate and duration of operation was performed. These results were further analysed
      in regard to the level of training of the participating surgeons. MATERIAL AND
      METHODS: A retrospective analysis of 1423 venous access port implantations
      between 1998 and 2008 was performed. RESULTS: The rate of total complications was
      13.8%. Among 4.7% early complications pneumothorax was the most common. The rate
      of late complications was 9.1%. Most common were infection (4.9%) followed by
      dysfunction of the catheter (3.5%). 1322 venous access port implantations were
      performed using puncture of the subclavian vein and Seldinger's technique. 101
      operations were performed by direct access through dissection of the cephalic
      vein and open introduction of the catheter. Operation time in the open group was
      significantly longer than in the puncture group (46.5 min vs. 38.7 min, p =
      0.005). There were significantly more late complications (9.6% vs. 2%, p = 0.01)
      and total complications (14.5% vs. 4%, p = 0.005) in the puncture group vs. the
      open access group. Primary success rates of open access vs. puncture were 100%
      and 96.8%, respectively. The rate of complications was independent of the
      experience status of the surgeon. However, the rate of total and late
      complications significantly decreases with number of performed operations.
      CONCLUSION: Venous port implantation is a relatively simple procedure despite its
      possible complications. An open access technique is safer than puncture. The rate
      of complications significantly decreases with increasing number of performed
      operations. Therefore venous port implantation and especially the open access
      method is an ideal teaching operation in a structured surgical training
      programme.

PMID- 25076164
TI  - [Lung cancer: is surgery an option for persisting N2 after induction therapy?].
AB  - BACKGROUND: Induction chemotherapy followed by surgical resection has been a
      treatment option for stage IIIA3 N2 non-small cell lung cancer since publication
      of some small randomised trials during the 1990s. Later on other studies
      suggested a poor prognosis in cases of persistent N2 disease, so surgical
      treatment for these patients was not recommended. This study analyses the outcome
      of patients with persisting N2 disease and tries to identify prognostic
      parameters within that group of patients. METHODS: We conducted a retrospective
      cohort study with 50 patients after induction therapy for stage IIIA N2 NSCLC. We
      analysed the influence of the postoperative lymph node involvement as well as the
      number of involved lymph nodes on the overall survival. RESULTS: 50 patients with
      potentially resectable stage IIIA N2 were included in the analysis. In 25 cases
      (50 %) a persisting N2 remained after induction therapy with
      cisplatin/gemcitabine, 11 patients had a mediastinal downstaging. 14 patients did
      not qualify for surgery because of disease progression or comorbidities. The
      resection consisted in 29 cases of a lobectomy or bilobectomy; two times
      pneumonectomy was necessary and 4 segmentectomies and one atypical resection were
      performed. The median survival of patients with persisting N2 (ypN2) was 14.6
      months, if mediastinal downstaging was achieved (ypN0/1) it was 22.3 months (p =
      0.172). The number of involved mediastinal lymph nodes was a significant
      prognostic factor. If less than 6 lymph nodes were involved the mean survival was
      17.5 months, while it was 8.6 months in patients with more than 6 involved lymph
      nodes (p < 0.01). CONCLUSIONS: The median survival for patients with persisting
      N2 disease is less favourable compared to patients with mediastinal downstaging.
      However, the long-term survival for patients with less than 6 involved lymph
      nodes is 17.5 months. Therefore surgical resection for these patients seems to be
      justified. After induction therapy a rigorous restaging should be performed to
      rule out persisting multilevel N2 disease.

PMID- 25076165
TI  - [Relevance of MRSA on a Visceral Surgical Intensive Care Unit].
AB  - Background: Resistance to antibiotics is a worldwide increasing problem. A well
      known example is methicillin resistant Staphylococcus aureus, MRSA. What is the
      relevance of MRSA on a surgical ICU? Patients/Material and Methods: On a 20 bed
      academic SICU/intermediate care ward 14,976 patients were treated in a seven-year
      period. We identified only 98 MRSA-positive patients. 56 (57 %) of them were
      merely colonised, 42 (43 %) suffered from an MRSA infection. A control group
      comprised 56 similar patients without MRSA detection. Results: Patients with MRSA
      infection had a higher mortality rate (OR 4.18; p = 0.002), but only 4 out of 20
      patients died due to the MRSA infection. APACHE 2 score of more than 20 was
      predictive for being colonised with MRSA (OR 3.08; p = 0.04), but it was not a
      risk factor for developing an MRSA infection (OR 1.03; p = 0.95). Patients with
      MRSA colonisation did not have a higher mortality rate than patients without.
      Conclusion: Outcome depended on severity of the disease, but not on the MRSA
      colonisation status. Patients with MRSA infection were more likely to die, but
      the reason of death rarely was MRSA.

PMID- 25076166
TI  - [Pancolitis Ulcerosa with 4 Associated Colorectal Carcinomas (Comment to Kuester
      et al.: "Synchronous Multifocal Colorectal Carcinoma in a Patient with Delayed
      Diagnosis of Ulcerative Pancolitis" in Pathol Res Pract 2008 [1])].

PMID- 25076168
TI  - Versatile coordination chemistry of a bis(methyliminophosphoranyl)pyridine ligand
      on copper centres.
AB  - The coordination of a bis(methyliminophosphoranyl)pyridine ligand (L) to copper
      centres was studied. The use of copper(I) bromide precursors gave access to
      [LCuBr] (2) in which only one iminophosphorane arm is coordinated to the metal,
      as observed by X-ray crystallography and MAS (31)P NMR. Its fluxional behaviour
      in solution was demonstrated by VT-(31)P NMR, and investigated by DFT
      calculations. On the other hand, coordination of L to [Cu(CH3CN)4]PF6 gave a
      dimer [L2Cu2](PF6)2 (3) in which the two copper centres do not have the same
      coordination sphere as shown by X-ray crystallography. Addition of a strong
      ligand such as PEt3 allows the preparation of a cationic monomeric copper complex
      (4) in which L has a behaviour similar to that observed for 2. Synthesis of
      copper(II) complexes was also achieved by chemical oxidation of 2, which shows an
      irreversible oxidation at -0.36 vs. Fc(+)/Fc, or directly via the coordination of
      L to CuBr2. In [LCuBr2] (5), L adopts a pincer coordination. Finally, the
      catalytic behaviour of copper(I) complexes 2 and 3 was investigated in
      cyclopropanation reactions and [3 + 2] cycloadditions.

PMID- 25076167
TI  - Map-based cloning and characterization of a brown planthopper resistance gene
      BPH26 from Oryza sativa L. ssp. indica cultivar ADR52.
AB  - The brown planthopper (BPH) is the most serious insect pest of rice in Asia. The
      indica rice cultivar ADR52 carries two BPH resistance genes, BPH26 (brown
      planthopper resistance 26) and BPH25. Map-based cloning of BPH26 revealed that
      BPH26 encodes a coiled-coil-nucleotide-binding-site-leucine-rich repeat (CC-NBS
      LRR) protein. BPH26 mediated sucking inhibition in the phloem sieve element.
      BPH26 was identical to BPH2 on the basis of DNA sequence analysis and feeding
      ability of the BPH2-virulent biotype of BPH. BPH2 was widely incorporated in
      elite rice cultivars and was well-cultivated in many Asian countries as a
      favorable gene resource in rice breeding against BPH. However, BPH2 was rendered
      ineffective by a virulent biotype of BPH in rice fields in Asia. In this study,
      we suggest that BPH2 can be reused by combining with other BPH resistance genes,
      such as BPH25, to ensure durable resistance to BPH.

PMID- 25076169
TI  - Effects of single and combined gabapentin use in elevated plus maze and forced
      swimming tests.
AB  - BACKGROUND: Gabapentin, a third-generation antiepileptic drug, is a structural
      analogue of gamma-aminobutyric acid, which is an important mediator of central
      nervous system. There is clinical data indicating its effectiveness in the
      treatment of psychiatric illnesses such as bipolar disorder and anxiety
      disorders. OBJECTIVES: We aimed to investigate the antidepressant and anxiolytic
      like effects and mechanisms of gabapentin in rats. MATERIAL AND METHODS: Female
      Spraque-Dawley rats weighing 250+/-20 g were used. A total of 13 groups were
      formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline
      (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg),
      gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline
      (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used
      intraperitoneally as single dose. Saline was administered to the control group.
      Elevated plus maze and forced swimming tests were used as experimental models of
      anxiety and depression, respectively. RESULTS: It was observed that gabapentin
      showed an anxiolytic-like and antidepressant-like effect in all doses in rats.
      Its antidepressant effect was found to be the same as the antidepressant effects
      of amitriptyline and sertraline. There was no change in the antidepressant effect
      when gabapentin was combined with amitriptyline and ketamine, but there was an
      increase when combined with sertraline and diazepam. Gabapentin and amitriptyline
      showed similar anxiolytic effect, whereas ketamine and diazepam had more potent
      anxiolytic effect compared with them. CONCLUSIONS: These data suggest that
      gabapentin may possess antidepressant- and anxiolytic-like effects.

PMID- 25076170
TI  - Environmental enrichment restores cognitive deficits induced by experimental
      childhood meningitis.
AB  - OBJECTIVE: To evaluate the influence of environmental enrichment (EE) on memory,
      cytokines, and brain-derived neurotrophic factor (BDNF) in the brain of adult
      rats subjected to experimental pneumococcal meningitis during infancy. METHODS:
      On postnatal day 11, the animals received either artificial cerebrospinal fluid
      (CSF) or Streptococcus pneumoniae suspension intracisternally at 1 * 10(6) CFU/mL
      and remained with their mothers until age 21 days. Animals were divided into the
      following groups: control, control + EE, meningitis, and meningitis + EE. EE
      began at 21 days and continued until 60 days of age (adulthood). EE consisted of
      a large cage with three floors, ramps, running wheels, and objects of different
      shapes and textures. At 60 days, animals were randomized and subjected to
      habituation to the open-field task and the step-down inhibitory avoidance task.
      After the tasks, the hippocampus and CSF were isolated for analysis. RESULTS: The
      meningitis group showed no difference in performance between training and test
      sessions of the open-field task, suggesting habituation memory impairment; in the
      meningitis + EE group, performance was significantly different, showing
      preservation of habituation memory. In the step-down inhibitory avoidance task,
      there were no differences in behavior between training and test sessions in the
      meningitis group, showing aversive memory impairment; conversely, differences
      were observed in the meningitis + EE group, demonstrating aversive memory
      preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were
      increased in the hippocampus, and BDNF levels in the CSF. CONCLUSIONS: The data
      presented suggest that EE, a non-invasive therapy, enables recovery from memory
      deficits caused by neonatal meningitis.

PMID- 25076171
TI  - Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania.
AB  - OBJECTIVE: To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5,
      in bipolar disorder (BD). METHODS: Forty patients with type I BD (18 in remission
      and 22 in mania) and 25 healthy controls matched for age, gender, and educational
      attainment were enrolled in this study. All subjects were assessed by the Mini
      International Neuropsychiatric Interview; the Young Mania Rating Scale and the
      Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD
      patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: BD patients in mania presented decreased NT
      4/5 plasma levels in comparison with controls (p < 0.05). There were no
      significant differences in NT-3 plasma levels between BD patients and controls.
      CONCLUSION: These findings corroborate the view that neurotrophin dysfunction is
      associated with mood states in patients with BD.

PMID- 25076172
TI  - Synthesis, structure and luminescence properties of new chloro-germanate
      phosphors Ca3GeO4Cl2:Eu2+.
AB  - A kind of novel blue-emitting chloro-germanate phosphor Ca3GeO4Cl2:Eu(2+) has
      been synthesized via a high temperature solid-state method. The crystal structure
      of the as-prepared phosphor was discussed from the viewpoint of the doping
      behaviors of the activators. The luminescence properties and thermal stability of
      Ca3GeO4Cl2:Eu(2+) was investigated in detail. Ca3GeO4Cl2:Eu(2+) phosphors exhibit
      a broad-band excitation band in the near ultra-violet region and a blue emission
      peak at 428 nm, which are both ascribed to the 4f-5d transitions of the Eu(2+)
      ions. The optimum concentration of Eu(2+) in the Ca3GeO4Cl2 phosphor was
      determined to be 3 mol%, and the concentration quenching mechanism was considered
      to be the dipole-dipole interaction with a critical distance of R(c) = 22.11 A.
      Thermal stability studies show that the photoluminescence intensity of the
      Ca3GeO4Cl2:Eu(2+) phosphor at 150  degrees C was 77% of the initial value at room
      temperature. The activation energy, E, was calculated to be 0.163 eV suggesting
      good thermal stability. The variation in lifetime of Ca3GeO4Cl2:Eu(2+) phosphor
      was also discussed to verify different luminescence centers in the lattice.

PMID- 25076173
TI  - The effectiveness of pneumoreduction for intussusception.
AB  - INTRODUCTION: To detect the effectiveness of pneumoreduction (PR) in
      intussusception, which is one the most common reasons of abdominal pain in
      infancy and childhood. METHODS: The records of patients treated in our clinic for
      intussusception between January 2005 and June 2012 were reviewed retrospectively.
      There were 150 patients aged between 2 months - 12 years of age; 48% (72) were
      girls, 52% (78) were boys. RESULTS: The most common complaint and clinical
      findings were abdominal pain (94,6%), vomiting (82.6%), rectal bleeding (81.3%),
      and discomfort (70.9%). An abdominal mass was observed in 73.3% of patients. PR
      was successfully performed in 86% of patients. It was carried out once in 86% of
      these patients and twice in 8.1%. PR was unsuccessful in six patients and they
      underwent surgery. Manual reduction (31 or 67.4% of operated patients) and
      resection - anastomosis (15 or 32.6 % of patients) were performed by surgery.
      Perforation occured in two patients (1.3%) during manual reduction. CONCLUSION:
      PR is an effective method in the treatment of intussusception with a high success
      ratio and a low complication ratio. It was possible to perform the procedure
      especially in patients who came in the early stage of the condition.

PMID- 25076174
TI  - Portable shade structure use at a youth soccer camp.

PMID- 25076175
TI  - Intramural hematoma occurring after coronary stenting.

PMID- 25076176
TI  - Transition from residency to practice: life does get better!

PMID- 25076178
TI  - Elevated blood pressure and obesity in childhood: a cross-sectional evaluation of
      4,609 schoolchildren.
AB  - BACKGROUND: The incidence of obesity in children is increasing worldwide,
      primarily in urbanized, high-income countries, and hypertension development is a
      detrimental effect of this phenomenon. OBJECTIVE: In this cross-sectional study,
      we evaluated the prevalence of excess weight and its association with high blood
      pressure (BP) in schoolchildren. METHODS: Here 4,609 male and female children,
      aged 6 to 11 years, from 24 public and private schools in Maringa, Brazil, were
      evaluated. Nutritional status was assessed by body mass index (BMI) according to
      cutoff points adjusted for sex and age. Blood pressure (BP) levels above 90th
      percentile for gender, age and height percentile were considered elevated.
      RESULTS: The prevalence of excess weight among the schoolchildren was 24.5%;
      16.9% were overweight, and 7.6% were obese. Sex and socioeconomic characteristics
      were not associated with elevated BP. In all age groups, systolic and diastolic
      BP correlated with BMI and waist and hip measurements, but not with waist-hip
      ratio. The prevalence of elevated BP was 11.2% in eutrophic children, 20.6% in
      overweight children [odds ratio (OR), 1.99; 95% confidence interval (CI), 1.61
      2.45], and 39.7% in obese children (OR, 5.4; 95% CI, 4.23-6.89). CONCLUSION:
      Obese and overweight children had a higher prevalence of elevated BP than normal
      weight children. Our data confirm that the growing worldwide epidemic of excess
      weight and elevated BP in schoolchildren may also be ongoing in Brazil.

PMID- 25076179
TI  - Investigation route of the coronary patient in the public health system in
      Curitiba, Sao Paulo and in InCor--IMPACT study.
AB  - BACKGROUND: The investigation of stable coronary artery disease (CAD) and its
      treatment depend on risk stratification for decision-making on the need for
      cardiac catheterization and revascularization. OBJECTIVE: To analyze the
      procedures used in the diagnosis and invasive treatment of patients with CAD, at
      the Brazilian Unified Health System (SUS) in the cities of Curitiba, Sao Paulo
      and at InCor-FMUSP. METHODS: Retrospective, descriptive, observational study of
      the diagnostic and therapeutic itineraries of the Brazilian public health care
      system patient, between groups submitted or not to prior noninvasive tests to
      invasive cardiac catheterization. Stress testing, stress echocardiography,
      perfusion scintigraphy, catheterization and percutaneous or surgical
      revascularization treatment procedures were quantified and the economic impact of
      the used strategies. RESULTS: There are significant differences in the assessment
      of patients with suspected or known CAD in the metropolitan region in the three
      scenarios. Although functional testing procedures are most often used the direct
      costs of these procedures differ significantly (6.1% in Curitiba, 20% in Sao
      Paulo and 27% in InCor-FMUSP). Costs related to the procedures and invasive
      treatments represent 59.7% of the direct costs of SUS in Sao Paulo and 87.2% in
      Curitiba. In InCor-FMUSP, only 24.3% of patients with stable CAD submitted to
      CABG underwent a noninvasive test before the procedure. CONCLUSION: Although
      noninvasive functional tests are the ones most often requested for the assessment
      of patients with suspected or known CAD most of the costs are related to invasive
      procedures/treatments. In most revascularized patients, the documentation of
      ischemic burden was not performed by SUS.

PMID- 25076177
TI  - Functional polymers of gene delivery for treatment of myocardial infarct.
AB  - Ischemic heart disease is rapidly growing as the common cause of death in the
      world. It is a disease that occurs as a result of coronary artery stenosis and is
      caused by the lack of oxygen within cardiac muscles due to an imbalance between
      oxygen supply and demand. The conventional medical therapy is focused on the use
      of drug eluting stents, coronary-artery bypass graft surgery and anti-thrombosis.
      Gene therapy provides great opportunities for treatment of cardiovascular
      disease. In order for gene therapy to be successful, the development of proper
      gene delivery systems and hypoxia-regulated gene expression vectors is the most
      important factors. Several non-viral gene transfer methods have been developed to
      overcome the safety problems of viral transduction. Some of which include
      plasmids that regulate gene expression that is controlled by environment specific
      promoters in the transcriptional or the translational level. This review explores
      polymeric gene carriers that target the myocardium and hypoxia-inducible vectors,
      which regulate gene expression in response to hypoxia, and their application in
      animal myocardial infarction models. 

PMID- 25076180
TI  - Do diabetic patients with acute coronary syndromes have a higher threshold for
      ischemic pain?
AB  - BACKGROUND: Data from over 4 decades have reported a higher incidence of silent
      infarction among patients with diabetes mellitus (DM), but recent publications
      have shown conflicting results regarding the correlation between DM and presence
      of pain in patients with acute coronary syndromes (ACS). OBJECTIVE: Our primary
      objective was to analyze the association between DM and precordial pain at
      hospital arrival. Secondary analyses evaluated the association between
      hyperglycemia and precordial pain at presentation, and the subgroup of patients
      presenting within 6 hours of symptom onset. METHODS: We analyzed a prospectively
      designed registry of 3,544 patients with ACS admitted to a Coronary Care Unit of
      a tertiary hospital. We developed multivariable models to adjust for potential
      confounders. RESULTS: Patients with precordial pain were less likely to have DM
      (30.3%) than those without pain (34.0%; unadjusted p = 0.029), but this
      difference was not significant after multivariable adjustment, for the global
      population (p = 0.84), and for subset of patients that presented within 6 hours
      from symptom onset (p = 0.51). In contrast, precordial pain was more likely among
      patients with hyperglycemia (41.2% vs 37.0% without hyperglycemia, p = 0.035) in
      the overall population and also among those who presented within 6 hours (41.6%
      vs. 32.3%, p = 0.001). Adjusted models showed an independent association between
      hyperglycemia and pain at presentation, especially among patients who presented
      within 6 hours (OR = 1.41, p = 0.008). CONCLUSION: In this non-selected ACS
      population, there was no correlation between DM and hospital presentation without
      precordial pain. Moreover, hyperglycemia correlated significantly with pain at
      presentation, especially in the population that arrived within 6 hours from
      symptom onset.

PMID- 25076181
TI  - Combination therapy for the cardiovascular effects of perinatal lead exposure in
      young and adult rats.
AB  - BACKGROUND: Combination therapy can play a significant role in the amelioration
      of several toxic effects of lead (Pb) and recovery from associated cardiovascular
      changes. OBJECTIVE: To investigate the effects of combination therapy on the
      cardiovascular effects of perinatal lead exposure in young and adult rats
      Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb
      during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were
      or were not exposed to Pb in the perinatal period received meso
      dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of
      these compounds for 30 additional days. Noradrenaline response curves were
      plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats
      stratified by perinatal Pb exposure (exposed/unexposed) and treatment received
      (treated/untreated). RESULTS: Systolic blood pressure was evaluated and shown to
      be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in
      the corresponding control age groups: 117.8 +/- 3.9*, 135.2 +/- 1.3*, 139.6 +/-
      1.6*, and 131.7 +/- 2.8*, respectively and 107.1 +/- 1.8, 118.8 +/- 2.1, 126.1 +/
      1.1, and 120.5 +/- 2.2, respectively (p < 0.05). Increased reactivity to
      noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and
      100-day-old exposed rats, and the maximum responses (g of tension) in the
      respective Pb-exposed and control age groups were as follows: 3.43 +/- 0.16*,
      4.32 +/- 0.18*, and 4.21 +/- 0.23*, respectively and 2.38 +/- 0.33, 3.37 +/-
      0.13, and 3.22 +/- 0.21, respectively (p < 0.05). CONCLUSIONS: All treatments
      reversed the changes in vascular reactivity to noradrenaline in rats perinatally
      exposed to Pb. The combination therapy resulted in an earlier restoration of
      blood pressure in Pb-exposed rats compared with the monotherapies, except for
      enalapril therapy in young rats. These findings represent a new approach to the
      development of therapeutic protocols for the treatment of Pb-induced
      hypertension.

PMID- 25076182
TI  - Survival and predictive factors of lethality in hemodialysis: D/I polymorphism of
      the angiotensin I-converting enzyme and of the angiotensinogen M235T genes.
AB  - BACKGROUND: End-stage kidney disease patients continue to have markedly increased
      cardiovascular disease morbidity and mortality. Analysis of genetic factors
      connected with the renin-angiotensin system that influences the survival of the
      patients with end-stage kidney disease supports the ongoing search for improved
      outcomes. OBJECTIVE: To assess survival and its association with the polymorphism
      of renin-angiotensin system genes: angiotensin I-converting enzyme
      insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis.
      METHODS: Our study was designed to examine the role of renin-angiotensin system
      genes. It was an observational study. We analyzed 473 chronic hemodialysis
      patients in four dialysis units in the state of Rio de Janeiro. Survival rates
      were calculated by the Kaplan-Meier method and the differences between the curves
      were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used
      logistic regression analysis and the multinomial model. A p value <= 0.05 was
      considered to be statistically significant. The local medical ethics committee
      gave their approval to this study. RESULTS: The mean age of patients was 45.8
      years old. The overall survival rate was 48% at 11 years. The major causes of
      death were cardiovascular diseases (34%) and infections (15%). Logistic
      regression analysis found statistical significance for the following variables:
      age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater
      than five times the minimum wage (p = 0.03089), the latter being a protective
      factor. CONCLUSIONS: The survival of hemodialysis patients is likely to be
      influenced by the TT of the angiotensinogen M235T gene.

PMID- 25076183
TI  - An organization of visual and auditory fear conditioning in the lateral amygdala.
AB  - Pavlovian fear conditioning is an evolutionary conserved and extensively studied
      form of associative learning and memory. In mammals, the lateral amygdala (LA) is
      an essential locus for Pavlovian fear learning and memory. Despite significant
      progress unraveling the cellular mechanisms responsible for fear conditioning,
      very little is known about the anatomical organization of neurons encoding fear
      conditioning in the LA. One key question is how fear conditioning to different
      sensory stimuli is organized in LA neuronal ensembles. Here we show that
      Pavlovian fear conditioning, formed through either the auditory or visual sensory
      modality, activates a similar density of LA neurons expressing a learning-induced
      phosphorylated extracellular signal-regulated kinase (p-ERK1/2). While the size
      of the neuron population specific to either memory was similar, the anatomical
      distribution differed. Several discrete sites in the LA contained a small but
      significant number of p-ERK1/2-expressing neurons specific to either sensory
      modality. The sites were anatomically localized to different levels of the
      longitudinal plane and were independent of both memory strength and the relative
      size of the activated neuronal population, suggesting some portion of the memory
      trace for auditory and visually cued fear conditioning is allocated differently
      in the LA. Presenting the visual stimulus by itself did not activate the same p
      ERK1/2 neuron density or pattern, confirming the novelty of light alone cannot
      account for the specific pattern of activated neurons after visual fear
      conditioning. Together, these findings reveal an anatomical distribution of
      visual and auditory fear conditioning at the level of neuronal ensembles in the
      LA. 

PMID- 25076184
TI  - Method to conjugate polysaccharide antigens to surfaces for the detection of
      antibodies.
AB  - A new generic method for the conjugation of lipopolysaccharide (LPS)-derived
      polysaccharide antigens from gram-negative bacteria has been developed using
      Salmonella as a model. After removal of lipid A from the LPS by mild acidolysis,
      the polysaccharide antigen was conjugated to polystyrene microbeads modified with
      N-alkyl hydroxylamine and N-alkyl-O-methyl hydroxylamine surface groups by
      incubation of antigen and beads for 16 h at 40  degrees C without the need for
      coupling agents. The efficiency of the new method was evaluated by flow cytometry
      in model samples and serum samples containing antibodies against Salmonella
      typhimurium and Salmonella dublin. The presented method was compared with a
      similar method for conjugation of Salmonella polysaccharide antigens to surfaces.
      Here, the new method showed higher antigen coupling efficiency by detecting low
      concentrations of antibodies. Furthermore, the polysaccharide-conjugated beads
      showed preserved bioactivity after 1 year of use.

PMID- 25076185
TI  - Comparison of a classical with a highly formularized body condition scoring
      system for dairy cattle.
AB  - Body condition scoring is a common tool to assess the subcutaneous fat reserves
      of dairy cows. Because of its subjectivity, which causes limits in repeatability,
      it is often discussed controversially. Aim of the current study was to evaluate
      the impact of considering the cows overall appearance on the scoring process and
      on the validity of the results. Therefore, two different methods to reveal body
      condition scores (BCS), 'independent BCS' (iBCS) and 'dependent BCS' (dBCS), were
      used to assess 1111 Swiss Brown Cattle. The iBCS and the dBCS systems were both
      working with the same flowchart with a decision tree structure for visual and
      palpatory assessment using a scale from 2 to 5 with increment units of 0.25. The
      iBCS was created strictly complying with the defined frames of the decision tree
      structure. The system was chosen due to its formularized approach to reduce the
      influence of subjective impressions. By contrast, the dBCS system, which was in
      line with common practice, had a more open approach, where - besides the decision
      tree - the overall impression of the cow's physical appearance was taken into
      account for generating the final score. Ultrasound measurement of the back fat
      thickness (BFT) was applied as a validation method. The dBCS turned out to be the
      better predictor of BFT, explaining 67.3% of the variance. The iBCS was only able
      to explain 47.3% of the BFT variance. Within the whole data set, only 31.3% of
      the animals received identical dBCS and iBCS. The pin bone region caused the most
      deviations between dBCS and iBCS, but also assessing the pelvis line, the hook
      bones and the ligaments led to divergences in around 20% of the scored animals.
      The study showed that during the assessment of body condition a strict adherence
      to a decision tree is a possible source of inexact classifications. Some body
      regions, especially the pin bones, proved to be particularly challenging for
      scoring due to difficulties in assessing them. All the more, the inclusion of the
      overall appearance of the cow into the assessment process counteracted these
      errors and led to a fair predictability of BFT with the flowchart-based BCS. This
      might be particularly important, if different cattle types and breeds are
      assessed.

PMID- 25076186
TI  - Human exposure to live poultry and psychological and behavioral responses to
      influenza A(H7N9), China.
AB  - To investigate human exposure to live poultry and changes in risk perception and
      behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed
      2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and
      found that perceived risk for influenza A(H7N9) was low. The highest rate of
      exposure to live poultry was reported in Guangzhou, where 47% of those surveyed
      reported visiting a live poultry market > or =1 times in the previous year. Most
      (77%) urban respondents reported that they visited live markets less often after
      influenza A(H7N9) cases were first identified in China in March 2013, but only
      30% supported permanent closure of the markets to control the epidemic. In rural
      areas, 48% of respondents reported that they raised backyard poultry. Exposure to
      live commercial and private poultry is common in urban and rural China and
      remains a potential risk factor for human infection with novel influenza viruses.

PMID- 25076187
TI  - Exploration and forecasting of behaviours and factors relating to fruit and
      vegetable intake among seniors in the community.
AB  - OBJECTIVE: The present study investigated the current status of fruit and
      vegetable intake among seniors and assessed the relationship between personal
      background factors, social psychological factors and environmental factors of the
      study participants and their fruit and vegetable consumption behaviour. DESIGN:
      Research data were collected through individual interviews using a questionnaire
      developed by the authors. SPSS for Windows 15.0 statistical software was used to
      process and analyse the data. SETTING: Elderly individuals sampled from all
      twenty-nine administration units of Keelung City's Renai District were
      interviewed. SUBJECTS: Study participants included 398 residents aged 65 years or
      older. RESULTS: On average, study participants ate five daily servings of fruits
      and vegetables on 2.86 d/week. The important variables influencing fruit and
      vegetable consumption were education level, outcome expectancy, social support,
      self-efficacy, frequency of dining out and role modelling. Educated participants
      consumed more fruits and vegetables than those without education. Outcome
      expectancy, social support, self-efficacy and role modelling had positive impacts
      on fruit and vegetable intake, but frequency of dining out had a negative impact
      on fruit and vegetable intake. The significant predictors of fruit and vegetable
      intake behaviour were education level, outcome expectancy, social support and
      frequency of dining out. Among those variables, social support was the most
      influential factor. CONCLUSIONS: Our findings supported the conclusion that
      health education strategies to increase fruit and vegetable intake among seniors
      should include the variables of social support and outcome expectancy.

PMID- 25076189
TI  - Rare occurrence of fatal Candida haemulonii peritonitis in a diabetic CAPD
      patient.
AB  - A 68-year-old diabetic chronic kidney disease patient on continuous ambulatory
      peritoneal dialysis for two years developed Candida haemulonii peritonitis
      without any predisposing factors. There is no effective treatment for this
      fungus. A peritoneal biopsy showed morphological changes of acute inflammation
      and chronicity.

PMID- 25076191
TI  - Tissue Healing Around Dental Implants With Marginal Bone Defects With and Without
      Flap Elevation: An Experimental Study in Dogs.
AB  - The technique of immediate implant placement after extraction has been conceived
      for preserving residual bone support and soft tissue morphology. Today, this
      procedure is still unpredictable and presents inconveniences for both the patient
      and the dentist. Therefore, the healing process around a dental implant placed
      into an extraction socket needs to be deeply investigated to increase the
      predictability of this surgical approach. The aim of the present investigation
      was to evaluate the healing of bone defects (fresh extraction sockets) after
      implant installation with flap elevation, and primary closure compared with
      implant installation without flap elevation. This study use histologic and
      histomorphometric analyses to evaluate tissue healing around dental implants with
      marginal bone defects with and without flap elevation 1 week, 4 weeks, and 12
      weeks after implantation in the dogs. The main qualitative findings showed that
      after 1 week of implantation almost no bone repair was observed, and there was no
      significant difference between the 2 groups in terms of bone-healing performance,
      inflammatory infiltrates (slight to moderate grade), and bone resorption
      (moderate to marked grade) limited to the coronal portion of the implanted sites.
      The 2 groups with or without flap elevation behaved similarly at this point of
      implantation. Under the experimental conditions of this study, no biological
      differences were observed between the 2 groups with and without flap elevation in
      terms of crestal bone repair, inflammation, marginal bone loss, and soft tissue
      downgrowth. The qualitative differences observed might be imputable to fortuitous
      events. The histomorphometric measurements confirmed the qualitative trends
      observed. The limitations of this study, as with all animal studies, are its
      translational aspects. Investigation of the same topic in a human population by
      setting up a controlled, randomized, prospective trial including a sufficient
      amount of patients investigated according to the split-mouth method would be
      beneficial. 

PMID- 25076190
TI  - Dietary supplementation of chinese ginseng prevents obesity and metabolic
      syndrome in high-fat diet-fed mice.
AB  - Obesity and diabetes are growing health problems worldwide. In this study,
      dietary provision of Chinese ginseng (0.5 g/kg diet) prevented body weight gain
      in high-fat (HF) diet-fed mice. Dietary ginseng supplementation reduced body fat
      mass gain, improved glucose tolerance and whole body insulin sensitivity, and
      prevented hypertension in HF diet-induced obese mice. Ginseng consumption led to
      reduced concentrations of plasma insulin and leptin, but had no effect on plasma
      adiponectin levels in HF diet-fed mice. Body temperature was higher in mice fed
      the ginseng-supplemented diet but energy expenditure, respiration rate, and
      locomotive activity were not significantly altered. Dietary intake of ginseng
      increased fatty acid oxidation in the liver but not in skeletal muscle.
      Expression of several transcription factors associated with adipogenesis
      (C/EBPalpha and PPARgamma) were decreased in the adipose tissue of HF diet-fed
      mice, effects that were mitigated in mice that consumed the HF diet supplemented
      with ginseng. Abundance of fatty acid synthase (FASN) mRNA was greater in the
      adipose tissue of mice that consumed the ginseng-supplemented HF diet as compared
      with control or un-supplemented HF diet-fed mice. Ginseng treatment had no effect
      on the expression of genes involved in the regulation of food intake in the
      hypothalamus. These data suggest that Chinese ginseng can potently prevent the
      development of obesity and insulin resistance in HF diet-fed mice.

PMID- 25076192
TI  - Cervical Spine Motion during Transfer and Stabilization Techniques.
AB  - Abstract Objectives. To compare paramedics' ability to minimize cervical spine
      motion during patient transfer onto a vacuum mattress with two stabilization
      techniques (head squeeze vs. trap squeeze) and two transfer methods (log roll
      with one assistant (LR2) vs. 3 assistants (LR4)). Methods. We used a crossover
      design to minimize bias. Each lead paramedic performed 10 LR2 transfers and 10
      LR4 transfers. For each of the 10 LR2 and 10 LR4 transfers, the lead paramedic
      stabilized the cervical spine using the head squeeze technique five times and the
      trap squeeze technique five times. We randomized the order of the stabilization
      techniques and LR2/LR4 across lead paramedics to avoid a practice or fatigue
      effect with repeated trials. We measured relative cervical spine motion between
      the head and trunk using inertial measurement units placed on the forehead and
      sternum. Results. On average, total motion was 3.9 degrees  less with three
      assistants compared to one assistant (p = 0.0002), and 2.8 degrees  less with the
      trap squeeze compared to the head squeeze (p = 0.002). There was no interaction
      between the transfer method and stabilization technique. When examining specific
      motions in the six directions, the trap squeeze generally produced less lateral
      flexion and rotation motion but allowed more extension. Examining within
      paramedic differences, some paramedics were clearly more proficient with the trap
      squeeze technique and others were clearly more proficient with the head squeeze
      technique. Conclusion. Paramedics performing a log roll with three assistants
      created less motion compared to a log roll with only one assistant, and using the
      trap squeeze stabilization technique resulted in less motion than the head
      squeeze technique but the clinical relevance of the magnitude remains unclear.
      However, large individual differences suggest future paramedic training should
      incorporate both best evidence practice as well as recognition that there may be
      individual differences between paramedics.

PMID- 25076193
TI  - Membranotropic regions of the dengue virus prM protein.
AB  - The Dengue virus (DENV) prM protein consists of two moieties, the pr and M
      domains. Apart from preventing the premature fusion activity of the DENV E
      protein, prM has several other unknown biological roles, displaying both protein
      protein and membrane-protein interactions. Although the prM protein is an
      essential component of the DENV viral cycle, little is known about its biological
      functions and what regions of this protein are responsible for said functions. By
      performing an exhaustive study of membrane rupture induced by a prM peptide
      library on simple and complex model membranes as well as their ability to
      modulate the phospholipid phase transitions of 1,2-dimyristoyl-sn-glycero-3
      phosphatidylcholine and 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-glycerol], we
      identified six membranotropic regions on the prM protein. Apart from the
      previously identified two transmembrane segments of the protein, one of these
      regions probably interacts with the fusion E protein and another one, the stem
      segment, would interact with the membrane modulating its structure. These data
      will help us understand the molecular mechanism of viral entry and morphogenesis,
      allow the identification of new targets for the treatment of Dengue virus
      infection, and make possible the future development of DENV entry inhibitors. 

PMID- 25076194
TI  - Stunned: ectopic pregnancy loss.

PMID- 25076195
TI  - Pyrrolo[3,2-b]quinoxaline derivatives as types I1/2 and II Eph tyrosine kinase
      inhibitors: structure-based design, synthesis, and in vivo validation.
AB  - The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase
      in complex with two type I inhibitors previously discovered in silico (compounds
      A and B) were used to design type I1/2 and II inhibitors. Chemical synthesis of
      about 25 derivatives culminated in the discovery of compounds 11d (type I1/2),
      7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases
      in vitro and a good selectivity profile on a panel of 453 human kinases (395
      nonmutant). Surface plasmon resonance measurements show a very slow unbinding
      rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II
      binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the
      inhibitor is deeply buried in a cavity originating from the displacement of the
      Phe side chain of the so-called DFG motif as observed in the crystal structure of
      compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast
      cancer xenograft. 

PMID- 25076196
TI  - Natural products and their derivatives regulating the janus kinase/signal
      transducer and activator of transcription pathway.
AB  - Janus kinase/signal transducer and activator of transcriptions (JAK/STAT)
      signaling pathway is one of the major signaling pathways involved in a variety of
      human physiological and pathological process. The proteins of JAK/STAT pathway or
      interferon response element (such as JAK, STAT, Src, SOCS, 2'5'-OAS, and ISRE)
      might be as drug targets for the study of physiological processes and treatment
      of related diseases, including cell proliferation, differentiation, apoptosis and
      immune processes, inflammation, cancer, arthritis, asthma, diabetes, and other
      diseases. This review attempts to summarize the current status of natural
      products and their derivatives (2002-2013) regulating the proteins or
      transcription elements of JAK/STAT signaling pathway to supply a new direction or
      drug targets for the discovery of new drugs. 

PMID- 25076197
TI  - AM last page. OneHealth: A Paradigm for Interdisciplinary Collaboration.

PMID- 25076198
TI  - AM last page. A comparison of three health care education collaboration and
      publication portals.

PMID- 25076200
TI  - Social media and medical professionalism: rethinking the debate and the way
      forward.
AB  - This Perspective addresses the growing literature about online medical
      professionalism. Whereas some studies point to the positive potential of social
      media to enhance and extend medical practice, the dominant emphasis is on the
      risks and abuses of social media. Overall evidence regarding online medical
      professionalism is (as with any new area of practice) limited; however, simply
      accumulating more evidence, without critically checking the assumptions that
      frame the debate, risks reinforcing negativity toward social media. In this
      Perspective, the author argues that the medical community should step back and
      reconsider its assumptions regarding both professionalism and the digital world
      of social media. Toward this aim, she outlines three areas for critical
      rethinking by educators and students, administrators, professional associations,
      and researchers. First she raises some cautions regarding the current literature
      on using social media in medical practice, which sometimes leaps too quickly from
      description to prescription. Second, she discusses professionalism. Current
      debates about the changing nature and contexts of professionalism generally might
      be helpful in reconsidering notions of online medical professionalism
      specifically. Third, the author argues that the virtual world itself and its
      built-in codes deserve more critical scrutiny. She briefly summarizes new
      research from digital studies both to situate the wider trends more critically
      and to appreciate the evolving implications for medical practice. Next, the
      author revisits the potential benefits of social media, including their
      possibilities to signal new forms of professionalism. Finally, the Perspective
      ends with specific suggestions for further research that may help move the debate
      forward.

PMID- 25076199
TI  - Community college pathways: improving the U.S. physician workforce pipeline.
AB  - PURPOSE: To examine the association between participation in a community college
      (CC) pathway, medical school admission, and intentions to practice in underserved
      communities or work with minority populations. METHOD: The authors performed
      cross-sectional analyses of the 2012 Association of American Medical Colleges
      matriculant and applicant files and the Matriculating Student Questionnaire to
      assess associations between student characteristics and participation in a CC
      pathway. They used logistic regression to estimate the association among CC
      pathway and acceptance to medical school, intention to practice in underserved
      areas, or intention to work with minority populations. RESULTS: There were 40,491
      applicants and 17,518 matriculants to U.S. MD-granting schools; about one-third
      used a CC. A higher proportion of underrepresented minority (URM) matriculants
      used CC pathways compared with whites. Applicants who attended a CC after high
      school and before a four-year university (First-CC) had lower odds of acceptance
      into medical school (adjusted odds ratio [AOR] = 0.68; 95% CI 0.61-0.75; P <
      .05). Compared with medical students who never attended a CC, First-CC
      matriculants were more likely to have parents without a college education
      (304/895 [34%] versus 1,683/12,598 [13%], P < .001) and higher odds of intentions
      to practice in underserved communities (AOR = 1.26; 95% CI 1.04-1.53; P < .05),
      after adjusting for covariates. CONCLUSIONS: There is both high representation of
      URM students and higher prevalence of intention to work with underserved
      communities among CC pathway participants. These findings may be of interest to
      those seeking to enhance diversity in the physician workforce.

PMID- 25076201
TI  - The community college pathway to medical school: a road less traveled.
AB  - Underrepresented minority and first-generation college students are more likely
      than white students to attend a community college before transferring to a four
      year school. Talamantes and colleagues report in this issue that, according to
      their study of 2012 medical school applicants and matriculants, community-college
      first applicants were significantly less likely to be admitted to medical school
      even after other important predictors, including grade point average and Medical
      College Admission Test scores, were taken into consideration. These findings
      suggest that rather than appreciating the "distance traveled" and obstacles
      overcome by applicants who got their start at a community college, medical school
      admissions committees may be consciously or subconsciously discounting their
      achievements. The authors of this Commentary consider the study by Talamantes and
      colleagues as well as other recent data related to community college graduates
      and emphasize that community colleges attract many high-achieving applicants who
      for any of several reasons-limited finances, inadequate advising, insufficient
      financial aid, or a need to stay close to home-choose not to enroll in a four
      year college right away. They argue that if medical school leaders are serious
      about lowering the social, racial, and economic barriers to medical school, they
      must start viewing two years of premedical education at a community college as an
      asset rather than a liability. 

PMID- 25076202
TI  - Climbing social media in medicine's hierarchy of needs.
AB  - The social media and medicine landscape is evolving rapidly. Early research,
      social media policies, and educational efforts focused on risk avoidance, while
      more current efforts have encouraged reflection and explored opportunities. This
      trajectory has affirmed physicians' professional commitment to maintaining public
      trust in the face of new challenges in the digital age. In this Commentary, the
      authors propose viewing physicians' social media use as a hierarchy of needs,
      similar to Maslow's psychological theory which posits that more basic levels of
      needs must be met before higher, aspirational levels can be fully attained. The
      three levels in the social media in medicine's hierarchy of needs are Security,
      Reflection, and Discovery. Critical to this model is respecting the essential
      need for Security in order to move towards Reflection and into Discovery. The
      social media in medicine hierarchy of needs pyramid rests on a foundation of
      Public Trust. How physicians as a profession have responded to past--and continue
      to respond to present and future--social media challenges to professionalism
      reveals what matters most: maintaining public trust and honoring the physicians'
      contract with society. A victory for online professionalism would be providing
      trainees with the tools and guidance needed to ascend to Discovery, while
      ensuring that their basic social media needs are first met. To do this, physician
      educators need to continue increasing trainees' awareness through designing
      relevant curricula, encouraging reflection, and providing positive role modeling
      and effective mentorship.

PMID- 25076203
TI  - NH(2-) dianion entrapped in a nanoporous 12CaO.7Al2O3 crystal by ammonothermal
      treatment: reaction pathways, dynamics, and chemical stability.
AB  - Inorganic imides are useful for hydrogen storage and base-catalyzed reactions but
      are extremely unstable under ambient conditions, which hinders their practical
      use as functional materials. Here, we demonstrate that NH2(-) and H(-), as well
      as NH(2-), can be incorporated into the nanocages of the mayenite crystals,
      [Ca24Al28O64](4+)(e(-))4 and [Ca24Al28O64](4+)(O(2-))2, by ammonothermal
      treatment. We evaluated the reaction conditions and found that the anion exchange
      reaction proceeded at higher than 500  degrees C. Raman spectroscopy showed that
      the N-H band position of encaged NH(2-) was close to that of CaNH and MgNH
      crystals. We also studied the reaction pathways that yield NH2(-) and NH(2-)
      anions and their dynamic motions by (1)H NMR spectroscopy. Successive reactions
      of encaged e(-) and O(2-) ions with NH3 yielded NH2(-), NH(2-), and H(-) or OH(
      ), in which the O(2-) ion reacted more efficiently with NH3. The maximum NH(2-)
      concentration and content were ~2.7 * 10(20) cm(-3) and ~0.25 (wt %)NH,
      respectively. The short spin-lattice relaxation time found in (1)H NMR suggests
      that the incorporated NH2(-) and NH(2-) rotate or librate in the cage near room
      temperature. Stability tests showed that the encaged NH(2-) ions are chemically
      stable under ambient conditions and in organic solvents. These results are
      attributed to the encapsulation of active anions within subnanometer-sized cages
      composed of Ca-O-Al oxide frameworks. The encaged NH(2-) desorbed as NH3 at
      higher than 500  degrees C under vacuum (Ea = 172 kJ mol(-1)). It is thus
      expected that C12A7:NH(2-) will function as a reactive nitrogen source for
      nitrogen transfer reactions by in situ cage degradation. 

PMID- 25076204
TI  - Bismuth-catalyzed synthesis of polycyclic aromatic hydrocarbons (PAHs) with a
      phenanthrene backbone via cyclization and aromatization of 2-(2-arylphenyl)vinyl
      ethers.
AB  - The reaction of 2-(2-arylphenyl)vinyl ethers in the presence of a catalytic
      amount of bismuth(III) triflate gave substituted phenanthrenes in excellent
      yields under mild reaction conditions. The reaction was also applied to the
      construction of other polycyclic aromatic hydrocarbons (PAHs), such as chrysene,
      helicene, and pyrene having a phenanthrene backbone, via regioselective
      cyclization. This method has the advantages of easy availability of the
      cyclization precursors, operational simplicity, and high reaction efficiency. 

PMID- 25076206
TI  - Temperature effects on the scattering of polarons and bipolarons in organic
      conductors.
AB  - The scattering process between an electron-polaron and a hole-bipolaron has been
      simulated using a version of the Su-Schrieffer-Heeger (SSH) model modified to
      include an external electric field, Coulomb interactions, and temperature effects
      in the scope of nonadiabatic molecular dynamics. The simulations reveal
      remarkable details concerning the polaron-bipolaron recombination reaction. It is
      found that there exists a critical temperature regime below which a hole
      bipolaron and a mixed state composed by an electron-polaron and an exciton are
      formed and a hole-bipolaron and a free electron are the resulting products of the
      collisional process, if the temperature is higher than the critical value. In
      addition, it is obtained that both channels depend sensitively on the strength of
      the applied electric field. These significant results may provide guidance to
      understand processes regarding electroluminescence in polymer diodes. 

PMID- 25076205
TI  - Gene expression analysis of children with acute hematogenous osteomyelitis caused
      by Methicillin-resistant Staphylococcus aureus: correlation with clinical
      severity of illness.
AB  - Children with acute hematogenous osteomyelitis (AHO) demonstrate a broad spectrum
      of clinical manifestations, ranging from mild to severe. Several advances have
      been achieved in the study of host immune response to acute invasive
      Staphylococcus aureus infections through gene expression analysis. However,
      previous research has neither attempted to evaluate the response of children with
      AHO specific to Methicillin-resistant Staphylococcus aureus (MRSA) nor to
      correlate gene expression with clinical phenotype. Study objective was to
      correlate gene expression of children with AHO due to MRSA with clinical severity
      of illness. Whole blood samples were obtained in Tempus tubes from 12 children
      with osteomyelitis once cultures obtained directly from the site of infection
      confirmed to be positive for MRSA. Using an Illumina platform and a systems-wide
      modular analysis, microarray findings from ten of these children were compared to
      that of nine healthy (age, ethnicity and gender) matched controls and correlated
      with clinical severity of illness. Children with AHO from MRSA demonstrated over
      expression of innate immunity with respect to neutrophil activity, coagulation,
      inflammatory response, and erythrocyte development. Concurrently, these children
      demonstrated under-expression of adaptive immunity with respect to lymphocyte
      activation and activity of T-cell, cytotoxic or NK cell, and B-cell lines. Three
      over-expressed genes, P2RX1, SORT1, and RETN, and two under-expressed genes,
      LOC641788 and STAT 4, were significantly correlated with severity of illness.
      STAT 4 showed the strongest correlation (R2 = -0.83). STAT4 downregulation could
      potentially explain under-expression of genes related to adaptive immunity in
      this cohort of patients with AHO. This study identified specific genes which
      correspond to disease severity during the early hospitalization of children with
      AHO from MRSA. Pattern recognition of this combination of genes could help to
      identify in the future severe clinical phenotypes before the disease is fully
      manifest and direct appropriate attention and resources to those children. 

PMID- 25076207
TI  - Fibroblast alpha11beta1 integrin regulates tensional homeostasis in
      fibroblast/A549 carcinoma heterospheroids.
AB  - We have previously shown that fibroblast expression of alpha11beta1 integrin
      stimulates A549 carcinoma cell growth in a xenograft tumor model. To understand
      the molecular mechanisms whereby a collagen receptor on fibroblast can regulate
      tumor growth we have used a 3D heterospheroid system composed of A549 tumor cells
      and fibroblasts without (alpha11+/+) or with a deletion (alpha11-/-) in integrin
      alpha11 gene. Our data show that alpha11-/-/A549 spheroids are larger than
      alpha11+/+/A549 spheroids, and that A549 cell number, cell migration and cell
      invasion in a collagen I gel are decreased in alpha11-/-/A549 spheroids. Gene
      expression profiling of differentially expressed genes in fibroblast/A549
      spheroids identified CXCL5 as one molecule down-regulated in A549 cells in the
      absence of alpha11 on the fibroblasts. Blocking CXCL5 function with the CXCR2
      inhibitor SB225002 reduced cell proliferation and cell migration of A549 cells
      within spheroids, demonstrating that the fibroblast integrin alpha11beta1 in a 3D
      heterospheroid context affects carcinoma cell growth and invasion by stimulating
      autocrine secretion of CXCL5. We furthermore suggest that fibroblast alpha11beta1
      in fibroblast/A549 spheroids regulates interstitial fluid pressure by compacting
      the collagen matrix, in turn implying a role for stromal collagen receptors in
      regulating tensional hemostasis in tumors. In summary, blocking stromal
      alpha11beta1 integrin function might thus be a stroma-targeted therapeutic
      strategy to increase the efficacy of chemotherapy.

PMID- 25076208
TI  - Acceptability of using electronic vending machines to deliver oral rapid HIV self
      testing kits: a qualitative study.
AB  - INTRODUCTION: Rates of unrecognized HIV infection are significantly higher among
      Latino and Black men who have sex with men (MSM). Policy makers have proposed
      that HIV self-testing kits and new methods for delivering self-testing could
      improve testing uptake among minority MSM. This study sought to conduct
      qualitative assessments with MSM of color to determine the acceptability of using
      electronic vending machines to dispense HIV self-testing kits. MATERIALS AND
      METHODS: African American and Latino MSM were recruited using a participant pool
      from an existing HIV prevention trial on Facebook. If participants expressed
      interest in using a vending machine to receive an HIV self-testing kit, they were
      emailed a 4-digit personal identification number (PIN) code to retrieve the test
      from the machine. We followed up with those who had tested to assess their
      willingness to participate in an interview about their experience. RESULTS:
      Twelve kits were dispensed and 8 interviews were conducted. In general,
      participants expressed that the vending machine was an acceptable HIV test
      delivery method due to its novelty and convenience. DISCUSSION: Acceptability of
      this delivery model for HIV testing kits was closely associated with three main
      factors: credibility, confidentiality, and convenience. Future research is needed
      to address issues, such as user-induced errors and costs, before scaling up the
      dispensing method.

PMID- 25076209
TI  - Behavioural repertoire of working donkeys and consistency of behaviour over time,
      as a preliminary step towards identifying pain-related behaviours.
AB  - BACKGROUND: The donkey has a reputation for stoicism and its behavioural
      repertoire in clinical contexts is under-reported. Lack of understanding of the
      norms of donkey behaviour and how it may vary over time can compromise use of
      behavioural measures as indicators of pain or emotional state. The objective of
      this study was to find out whether the behaviour of working donkeys was
      influenced by gender, the time of day or differed between days with a view to
      assessing how robust these measures are for inclusion in a working donkey
      ethogram. METHODOLOGY/PRINCIPAL FINDINGS: Frequency and consistency of postural
      and event behaviours were measured in 21 adult working donkeys (12 females; 9
      males). Instantaneous (scan) and focal sampling were used to measure maintenance,
      lying, ingestive and investigative behaviours at hourly intervals for ten
      sessions on each of two consecutive days. High head carriage and biting were seen
      more frequently in male donkeys than females (P<0.001). Level head carriage,
      licking/chewing and head-shaking were observed more frequently in female donkeys
      (P<0.001). Tail position, ear orientation, foot stamping, rolling/lying and head
      shaking behaviours were affected by time of day (P<0.001). However, only two
      variations in ear orientation were found to be significantly different over the
      two days of observations (P<0.001). Tail swishing, head shaking, foot stamping,
      and ears held sideways and downwards were significantly correlated (P<0.001) and
      are assumed to be behaviours to discourage flies. CONCLUSIONS/SIGNIFICANCE: All
      donkeys expressed an extensive behavioural repertoire, although some differences
      in behaviour were evident between genders. While most behaviours were consistent
      over time, some behaviours were influenced by time of day. Few behaviours
      differed between the two test days. The findings can be used to inform the
      development of a robust, evidence-based ethogram for working donkeys.

PMID- 25076212
TI  - Computer simulations of dendrimer-polyelectrolyte complexes.
AB  - We carry out a systematic analysis of static properties of the clusters formed by
      complexation between charged dendrimers and linear polyelectrolyte (LPE) chains
      in a dilute solution under good solvent conditions. We use single chain in mean
      field simulations and analyze the structure of the clusters through radial
      distribution functions of the dendrimer, cluster size, and charge distributions.
      The effects of LPE length, charge ratio between LPE and dendrimer, the influence
      of salt concentration, and the dendrimer generation number are examined. Systems
      with short LPEs showed a reduced propensity for aggregation with dendrimers,
      leading to formation of smaller clusters. In contrast, larger dendrimers and
      longer LPEs lead to larger clusters with significant bridging. Increasing salt
      concentration was seen to reduce aggregation between dendrimers as a result of
      screening of electrostatic interactions. Generally, maximum complexation was
      observed in systems with an equal amount of net dendrimer and LPE charges,
      whereas either excess LPE or dendrimer concentrations resulted in reduced
      clustering between dendrimers. 

PMID- 25076211
TI  - Discrimination contours for moving sounds reveal duration and distance cues
      dominate auditory speed perception.
AB  - Evidence that the auditory system contains specialised motion detectors is mixed.
      Many psychophysical studies confound speed cues with distance and duration cues
      and present sound sources that do not appear to move in external space. Here we
      use the 'discrimination contours' technique to probe the probabilistic
      combination of speed, distance and duration for stimuli moving in a horizontal
      arc around the listener in virtual auditory space. The technique produces a set
      of motion discrimination thresholds that define a contour in the distance
      duration plane for different combination of the three cues, based on a 3-interval
      oddity task. The orientation of the contour (typically elliptical in shape)
      reveals which cue or combination of cues dominates. If the auditory system
      contains specialised motion detectors, stimuli moving over different distances
      and durations but defining the same speed should be more difficult to
      discriminate. The resulting discrimination contours should therefore be oriented
      obliquely along iso-speed lines within the distance-duration plane. However, we
      found that over a wide range of speeds, distances and durations, the ellipses
      aligned with distance-duration axes and were stretched vertically, suggesting
      that listeners were most sensitive to duration. A second experiment showed that
      listeners were able to make speed judgements when distance and duration cues were
      degraded by noise, but that performance was worse. Our results therefore suggest
      that speed is not a primary cue to motion in the auditory system, but that
      listeners are able to use speed to make discrimination judgements when distance
      and duration cues are unreliable. 

PMID- 25076213
TI  - Simultaneous determination of binding constants for multiple carbohydrate hosts
      in complex mixtures.
AB  - We describe a simple method for the simultaneous determination of association
      constants for a guest binding to seven different hosts in a mixture of more than
      20 different oligosaccharides. If the binding parameters are known for one
      component in the mixture, a single NMR titration suffices to determine binding
      constants for all other detectable and resolvable hosts. With the use of high
      resolution (1)H-(13)C HSQC experiments, complexes of amphiphiles with more than
      10 different maltooligosaccharides can be resolved. Hereby, the binding
      capabilities of a set of structurally related hosts can be quantitatively studied
      to systematically explore noncovalent interactions without the need to isolate
      each host. 

PMID- 25076215
TI  - Thyroglossal duct cysts and obstructive sleep apnoea: three case reports and
      review of the literature.
AB  - BACKGROUND: Thyroglossal duct cysts and obstructive sleep apnoea are commonly
      occurring medical conditions which appear to present independently in patients.
      However, we noted three cases where the thyroglossal duct cysts influenced the
      development and/or therapy of obstructive sleep apnoea. In this article, these
      three case studies are presented, as is a study of the association between
      thyroglossal duct cysts and obstructive sleep apnoea, preceded by a literature
      review. CASE REPORTS: The patient in the first case study underwent
      hyoidthyroidpexia for obstructive sleep apnoea, which revealed an unexpected
      thyroglossal duct cyst. The second patient had previously undergone Sistrunk
      surgery for the removal of a thyroglossal duct cyst and subsequently presented
      with obstructive sleep apnoea. Finally, the third patient, who had previously
      undergone Sistrunk surgery, presented with obstructive sleep apnoea and underwent
      alternative surgery as hyoidthyroidpexia was no longer possible. CONCLUSION: To
      our knowledge, the association between thyroglossal duct cysts and obstructive
      sleep apnoea has not been addressed previously. The results indicate that the
      relationship is much stronger than previously thought, and further research is
      required to investigate the extent of the association and possible causal
      relations.

PMID- 25076214
TI  - Kinetic and sequence-structure-function analysis of LinB enzyme variants with
      beta- and delta-hexachlorocyclohexane.
AB  - Organochlorine insecticide hexachlorocyclohexane (HCH) has recently been
      classified as a 'Persistent Organic pollutant' by the Stockholm Convention. The
      LinB haloalkane dehalogenase is a key upstream enzyme in the recently evolved Lin
      pathway for the catabolism of HCH in bacteria. Here we report a sequence
      structure-function analysis of ten naturally occurring and thirteen synthetic
      mutants of LinB. One of the synthetic mutants was found to have ~80 fold more
      activity for beta- and delta-hexachlorocyclohexane. Based on detailed biophysical
      calculations, molecular dynamics and ensemble docking calculations, we propose
      that the latter variant is more active because of alterations to the shape of its
      active site and increased conformational plasticity. 

PMID- 25076216
TI  - Magnetic resonance properties of actinyl carbonate complexes and plutonyl(VI)
      tris-nitrate.
AB  - Electronic structures and magnetic properties of actinyl ions AnO2(n+) (An = U,
      Np, and Pu) and the equatorially coordinated carbonate complexes [UO2(CO3)3](5-),
      [NpO2(CO3)3](4-), and [PuO2(CO3)3](4-) are investigated by ab initio quantum
      chemical calculations. The complex [PuO2(NO3)3](-) is also included because of
      experimentally available g-factors and for comparison with a previous study of
      [NpO2(NO3)3](-) (Chem.-Eur. J. 2014, 20, 7994-8011). The results are rationalized
      with the help of crystal-field (CF)-type models with parameters extracted from
      the ab initio calculations, and with the help of natural orbitals and natural
      spin orbitals contributing to the magnetic properties and the unpaired spin
      distribution, generated from the spin-orbit wave functions. These orbitals
      resemble textbooklike representations of the actinide 5f orbitals. Calculated
      paramagnetic susceptibilities are used to estimate dipolar 13C chemical shifts
      for the carbonate ligands. Their signs and order of magnitude are compared to
      paramagnetic effects observed experimentally in NMR spectra. The results indicate
      that the experimental spectra are also influenced by contact shifts.

PMID- 25076218
TI  - A novel optimal configuration form redundant MEMS inertial sensors based on the
      orthogonal rotation method.
AB  - In order to improve the accuracy and reliability of micro-electro mechanical
      systems (MEMS) navigation systems, an orthogonal rotation method-based nine-gyro
      redundant MEMS configuration is presented. By analyzing the accuracy and
      reliability characteristics of an inertial navigation system (INS), criteria for
      redundant configuration design are introduced. Then the orthogonal rotation
      configuration is formed through a two-rotation of a set of orthogonal inertial
      sensors around a space vector. A feasible installation method is given for the
      real engineering realization of this proposed configuration. The performances of
      the novel configuration and another six configurations are comprehensively
      compared and analyzed. Simulation and experimentation are also conducted, and the
      results show that the orthogonal rotation configuration has the best reliability,
      accuracy and fault detection and isolation (FDI) performance when the number of
      gyros is nine. 

PMID- 25076217
TI  - Modulating drug resistance by targeting BCRP/ABCG2 using retrovirus-mediated RNA
      interference.
AB  - BACKGROUND: The BCRP/ABCG2 transporter, which mediates drug resistance in many
      types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus
      encoding a shRNA targeting the ATP-binding domain of this protein was used to
      screen for highly efficient agents that could reverse drug resistance and improve
      cell sensitivity to drugs, thus laying the foundation for further studies and
      applications. METHODOLOGY/PRINCIPAL FINDINGS: To target the ATP-binding domain of
      BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target
      sequences starting from the 270th, 745th and 939th bps of the 6th exon, were
      constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi) that
      conferred significant knockdown effects were screened using a drug-sensitivity
      experiment and flow cytometry. The human choriocarcinoma cell line JAR, which
      highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a
      hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR
      tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the
      tumor tissue was determined using immunohistochemistry, fluorescent quantitative
      RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2
      tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor
      tissue were determined using in situ hybridization. V-BCRPi increased the
      sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis
      promoting effects of 5-FU in the tumor. CONCLUSIONS/SIGNIFICANCE: The goal of the
      in vivo and in vitro studies was to screen for an RNA interference recombinant
      retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V
      BCRPi) to inhibit its function. A new method to improve the chemo-sensitivity of
      breast cancer and other tumor cells was discovered, and this method could be used
      for gene therapy and functional studies of malignant tumors.

PMID- 25076219
TI  - Thermal tracking of sports players.
AB  - We present here a real-time tracking algorithm for thermal video from a sports
      game. Robust detection of people includes routines for handling occlusions and
      noise before tracking each detected person with a Kalman filter. This online
      tracking algorithm is compared with a state-of-the-art offline multi-target
      tracking algorithm. Experiments are performed on a manually annotated 2-minutes
      video sequence of a real soccer game. The Kalman filter shows a very promising
      result on this rather challenging sequence with a tracking accuracy above 70% and
      is superior compared with the offline tracking approach. Furthermore, the
      combined detection and tracking algorithm runs in real time at 33 fps, even with
      large image sizes of 1920 * 480 pixels.

PMID- 25076220
TI  - The recovery of weak impulsive signals based on stochastic resonance and moving
      least squares fitting.
AB  - In this paper a stochastic resonance (SR)-based method for recovering weak
      impulsive signals is developed for quantitative diagnosis of faults in rotating
      machinery. It was shown in theory that weak impulsive signals follow the
      mechanism of SR, but the SR produces a nonlinear distortion of the shape of the
      impulsive signal. To eliminate the distortion a moving least squares fitting
      method is introduced to reconstruct the signal from the output of the SR process.
      This proposed method is verified by comparing its detection results with that of
      a morphological filter based on both simulated and experimental signals. The
      experimental results show that the background noise is suppressed effectively and
      the key features of impulsive signals are reconstructed with a good degree of
      accuracy, which leads to an accurate diagnosis of faults in roller bearings in a
      run-to failure test. 

PMID- 25076221
TI  - Calibration of an outdoor distributed camera network with a 3D point cloud.
AB  - Outdoor camera networks are becoming ubiquitous in critical urban areas of the
      largest cities around the world. Although current applications of camera networks
      are mostly tailored to video surveillance, recent research projects are
      exploiting their use to aid robotic systems in people-assisting tasks. Such
      systems require precise calibration of the internal and external parameters of
      the distributed camera network. Despite the fact that camera calibration has been
      an extensively studied topic, the development of practical methods for user
      assisted calibration that minimize user intervention time and maximize precision
      still pose significant challenges. These camera systems have non-overlapping
      fields of view, are subject to environmental stress, and are likely to suffer
      frequent recalibration. In this paper, we propose the use of a 3D map covering
      the area to support the calibration process and develop an automated method that
      allows quick and precise calibration of a large camera network. We present two
      cases of study of the proposed calibration method: one is the calibration of the
      Barcelona Robot Lab camera network, which also includes direct mappings
      (homographies) between image coordinates and world points in the ground plane
      (walking areas) to support person and robot detection and localization
      algorithms. The second case consist of improving the GPS positioning of geo
      tagged images taken with a mobile device in the Facultat de Matematiques i
      Estadistica (FME) patio at the Universitat Politecnica de Catalunya (UPC). 

PMID- 25076222
TI  - High performance relaxor-based ferroelectric single crystals for ultrasonic
      transducer applications.
AB  - Relaxor-based ferroelectric single crystals Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) have
      drawn much attention in the ferroelectric field because of their excellent
      piezoelectric properties and high electromechanical coupling coefficients
      (d33~2000 pC/N, kt~60%) near the morphotropic phase boundary (MPB). Ternary
      Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIN-PMN-PT) single crystals also
      possess outstanding performance comparable with PMN-PT single crystals, but have
      higher phase transition temperatures (rhombohedral to tetragonal Trt, and
      tetragonal to cubic Tc) and larger coercive field Ec. Therefore, these relaxor
      based single crystals have been extensively employed for ultrasonic transducer
      applications. In this paper, an overview of our work and perspectives on using
      PMN-PT and PIN-PMN-PT single crystals for ultrasonic transducer applications is
      presented. Various types of single-element ultrasonic transducers, including
      endoscopic transducers, intravascular transducers, high-frequency and high
      temperature transducers fabricated using the PMN-PT and PIN-PMN-PT crystals and
      their 2-2 and 1-3 composites are reported. Besides, the fabrication and
      characterization of the array transducers, such as phased array, cylindrical
      shaped linear array, high-temperature linear array, radial endoscopic array, and
      annular array, are also addressed. 

PMID- 25076223
TI  - A computational approach towards a gene regulatory network for the developing
      Nematostella vectensis gut.
AB  - BACKGROUND: The starlet sea anemone Nematostella vectensis is a diploblastic
      cnidarian that expresses a set of conserved genes for gut formation during its
      early development. During the last decade, the spatial distribution of many of
      these genes has been visualized with RNA hybridization or protein
      immunolocalization techniques. However, due to N. vectensis' curved and changing
      morphology, quantification of these spatial data is problematic. A method is
      developed for two-dimensional gene expression quantification, which enables a
      numerical analysis and dynamic modeling of these spatial patterns.
      METHODS/RESULT: In this work, first standardized gene expression profiles are
      generated from publicly available N. vectensis embryo images that display mRNA
      and/or protein distributions. Then, genes expressed during gut formation are
      clustered based on their expression profiles, and further grouped based on
      temporal appearance of their gene products in embryonic development.
      Representative expression profiles are manually selected from these clusters, and
      used as input for a simulation-based optimization scheme. This scheme iteratively
      fits simulated profiles to the selected profiles, leading to an optimized
      estimation of the model parameters. Finally, a preliminary gene regulatory
      network is derived from the optimized model parameters. OUTLOOK: While the focus
      of this study is N. vectensis, the approach outlined here is suitable for
      inferring gene regulatory networks in the embryonic development of any animal,
      thus allowing to comparatively study gene regulation of gut formation in silico
      across various species.

PMID- 25076224
TI  - Ethanol extract and isolated constituents from artemisia dracunculus inhibit
      esophageal squamous cell carcinoma and induce apoptotic cell death.
AB  - The objective of the present study was to examine the antitumor efficacy of the
      ethanol extract from Artemisia dracunculus as well as the compounds isolated from
      it on cultured EC-109 esophageal squamous cell carcinoma (ESCC) cells. Apoptotic
      activities of the compounds were also studied using flow cytometry. EC-109
      esophageal cancer cells were treated with varying concentrations of compounds 1-7
      isolated from the plant as well as the ethanol extract of Artemisia dracunculus.
      The cytotoxicity was evaluated by MTT assay and the apoptotic studies of the
      compounds were determined using flow-cytometry. Effect on mitochondrial membrane
      potential loss LambdaPsi m induced by compounds 2 and 4 was also studied in these
      cells. Bioassay-guided fractionation of the ethanol extract from the shoot and
      root parts of Artemisia dracunculus led to the isolation of 7-methoxycoumarin
      (1), scopoletin (2), dracumerin (3), sakuranetin (4), elimicin (5), davidigenin
      (6) and 6-methoxycapillarisin (7). All the compounds as well as the extract
      showed mild to potent cell proliferation inhibitory activities against the
      esophageal cell line. Sakuranetin and 6-methoxycapillarisin were found to have
      the most potent effects in inhibiting the cell proliferation. The 2 potent
      compounds, sakuranetin and 6-methoxycapillarisin were evaluated for their effects
      on cell cycle phase distribution (DNA damage) as well as their effects on
      mitochondrial membrane potential loss LambdaPsi m. Both compounds induced DNA
      damage as well as mitochondrial membrane potential loss in esophageal cancer
      cells. The study suggests that compounds, Sakuranetin and 6-methoxycapillarisin
      isolated from Artemisia dracunculus possess potent anticancer effects by inducing
      DNA damage in these cells. 

PMID- 25076225
TI  - Gabapentin Enhances Neurogenesis in E14 Rat Embryonic Neocortex Stem Cells.
AB  - Many anticonvulsant drugs have been studied for their non conventional
      therapeutic effects on neurodegerative diseases but merely a few demonstrated
      potential neurogenic characteristic. Gabapentin as a well-known mood stabilizer
      was studied for its potential capability to promote neurogenesis in embryonic rat
      cortical stem cells. Rat E14 cortical stem cells were exposed to gabapentin
      during differentiation for 7 days and subjected to immunocytochemistry. The
      phenotypic changes were evaluated in the ultimately survived and differentiated
      cells. Gabapentin (16 ug/ml) exposure significantly increased the number and
      percentage of MAP2 immunopositive neurons with no significant alterations in
      nestin or GFAP immunopositivity in neural or glial progenitors. The enhanced
      number of neurons by therapeutic doses of gabapentin via augmentation of the
      neuronal differentiation in neural stem cells may participate to the therapeutic
      properties of gabapentin in the treatment of mood disorder.

PMID- 25076226
TI  - Evaluation of apoptotic markers in HEI-OC1 cells treated with gentamicin with and
      without the mitochondria-targeted antioxidant mitoquinone.
AB  - HYPOTHESIS: Mitoquinone (MitoQ) attenuates aminoglycoside (AG)-induced
      upregulation of the proapoptotic molecules Bak and harakiri (Hrk) and decreases
      the percentage of apoptotic House Ear Institute Organ of Corti 1 (HEI-OC1) cells.
      BACKGROUND: The primary mechanism of AG ototoxicity is the formation of reactive
      oxygen species, which leads to hair cell death via apoptotic and nonapoptotic
      pathways. Antioxidants have been shown to protect against AG ototoxicity.
      Mitoquinone is a mitochondria-targeted derivative of the antioxidant ubiquinone.
      Thus, MitoQ may be more effective in preventing AG ototoxicity compared with
      untargeted antioxidants. METHODS: Ribonucleic acid from untreated HEI-OC1 cells
      and cells exposed to gentamicin with and without preincubation with MitoQ,
      idebenone (IDB, an untargeted ubiquinone), or decylTPP (positive control) were
      used to assess gene expression of Bak and Hrk using real-time polymerase chain
      reaction. Protein expression of Bak and Hrk was determined by Western blotting.
      Annexin V assay using flow cytometry was performed to assess the percentage of
      apoptotic HEI-OC1 cells treated with gentamicin with and without preincubation
      with MitoQ, decylTPP, or IDB. RESULTS: Preincubation of HEI-OC1 cells with MitoQ
      significantly decreased the gentamicin-induced upregulation of Bak gene (p =
      0.03) but not preincubation with IDB (p = 0.87). Harakiri levels were very low
      that relative quantification could not be carried out. Protein levels of Bak and
      Hrk were not different between treatments. Annexin V assay showed that gentamicin
      increased the percentage of apoptotic cells (p < 0.05) compared with control.
      However, the percentages of apoptotic cells in gentamicin-treated and cells
      pretreated with the antioxidants MitoQ or IDB were not different. CONCLUSION:
      Mitoquinone attenuated the gentamicin-induced upregulation of the Bak gene but
      not its product, the proapoptotic molecule Bak, and MitoQ did not significantly
      decrease the gentamicin-induced cell apoptosis in vitro. Further in vivo studies
      are needed to assess the clinical significance of these findings.

PMID- 25076227
TI  - Power reflectance as a screening tool for the diagnosis of superior semicircular
      canal dehiscence.
AB  - HYPOTHESIS: Power reflectance (PR) measurements in ears with superior canal
      dehiscence (SCD) have a characteristic pattern, the detection of which can assist
      in diagnosis. BACKGROUND: The aim of this study was to determine whether PR
      coupled with a novel detection algorithm can perform well as a fast, noninvasive,
      and easy screening test for SCD. The screening test aimed to determine whether
      patients with various vestibular and/or auditory symptom(s) should be further
      considered for more expensive and invasive tests that better define the diagnosis
      of SCD (and other third-window lesions). METHODS: Power reflectance was measured
      in patients diagnosed with SCD by high-resolution computed tomography. The study
      included 40 ears from 32 patients with varying symptoms (e.g., with and without
      conductive hearing loss, vestibular symptoms, and abnormal auditory sensations).
      RESULTS: Power reflectance results were compared to previously published norms
      and showed that SCD is commonly associated with a PR notch near 1 kHz. An
      analysis algorithm was designed to detect such notches and to quantify their
      incidence in affected and normal ears. Various notch detection thresholds yielded
      sensitivities of 80% to 93%, specificities of 69% to 72%, negative predictive
      values of 84% to 93%, and a positive predictive value of 67%. CONCLUSION: This
      study shows evidence that PR measurements together with the proposed notch
      detecting algorithm can be used to quickly and effectively screen patients for
      third-window lesions such as SCD in the early stages of a diagnostic workup.

PMID- 25076228
TI  - Percutaneous bone-anchored hearing implant surgery without soft-tissue reduction:
      up to 42 months of follow-up.
AB  - OBJECTIVE: To report the results of bone-anchored hearing implant (BAHI) surgery
      without soft-tissue reduction (WoSR); in our case, a series of 30 patients with a
      follow-up period of up to 42 months. PATIENTS: The study group included 30
      patients between ages 17 and 79 years, where BAHI was indicated, during a 42
      month period, between February 2010 and July 2013. Initially, only patients with
      medical comorbidities that could compromise wound healing were offered the
      procedure but, subsequently, all our patients are now offered this technique.
      INTERVENTION: Unlike in traditional techniques where all dermal and subcutaneous
      tissue and muscle are removed to enable the thinned skin to sit directly on the
      periosteum, here, in our series, using the WoSR technique, the soft tissue was
      preserved and only longer abutments (8.5, 9, and 12 mm) were used. MAIN OUTCOME
      MEASURE: Good early postoperative wound healing, absence of flap necrosis,
      absence of numbness around the surgical site, and trouble-free follow-up period,
      with 25 patients encountering no complications. RESULTS: Of the 30 patients, 25
      have had no postoperative problems and five had mild inflammation, of which three
      patients developed intractable pain and underwent soft-tissue reduction.
      CONCLUSION: The technique WoSR for BAHI surgery seems to be a safe technique with
      consistently good results, decreasing operating time and patient morbidity and
      avoiding some of the complications seen in traditional techniques using soft
      tissue reduction.

PMID- 25076229
TI  - Malleostapedotomy revisited: the advantages of malleus neck-anchoring
      malleostapedotomy.
AB  - OBJECTIVE: To extend our preliminary study by comparing the hearing outcomes of
      handle-malleostapedotomy (handle-MS; connecting the prosthesis to the malleus
      handle) and neck-MS (connecting the prosthesis to the malleus neck) in a larger
      case series. PATIENTS: Thirty-five patients who underwent MS at Seoul National
      University Hospital from January 1983 to December 2013. INTERVENTION: Review of
      pre- and postoperative audiometric data, intraoperative findings. MAIN OUTCOME
      MEASURES: Postoperative air-bone gap (ABG) and closure of ABG. RESULTS: In 11 of
      20 patients (55.0%) in the handle-MS group and 12 of 15 (80%) in the neck-MS
      group, the postoperative ABG closed to within 20 dB HL. For frequencies of 0.25,
      0.5, 1, 2, 3, and 4 kHz, the ABGs did not differ significantly between the two
      groups. The postoperative ABG closure was lower in the neck-MS group (22.3 +/-
      12.6 dB HL) than in the handle-MS group (23.5 +/- 11.6 dB HL), but without
      statistical significance (p = 0.78). Four patients in each group underwent MS as
      a revision procedure. One of them underwent neck-MS as revision surgery because
      of prosthesis extrusion after handle-MS. The mean ABG closure at 1 year
      postoperatively in patients who underwent revision neck-MS (19.9 +/- 11.9 dB HL)
      was not different from that of the patients who underwent revision handle-MS
      (20.9 +/- 8.7 dB HL). CONCLUSION: As neck-MS provided results comparable to those
      of handle-MS in our extended case series, it might be a useful procedure in
      selected cases of otosclerosis or stapes fixation with an incus anomaly,
      especially in revision cases after handle-MS.

PMID- 25076230
TI  - Role of K-ras mutation analysis in EUS-FNA samples obtained from pancreatic solid
      mass.

PMID- 25076231
TI  - Efficacy and safety of trastuzumab-based therapy in combination with different
      chemotherapeutic regimens in advanced esophagogastric cancer--a single cancer
      center experience.
AB  - BACKGROUND: Trastuzumab-based therapy has significantly changed the management of
      Her-2 positive metastatic esophagogastric cancer. However, only limited
      experience exists for the management in patients who are not suitable for
      cisplatin-based therapy. METHODS: Patients treated with trastuzumab in
      combination with different chemotherapeutic regimens were analyzed. Response
      rates, progression-free survival, overall survival, patterns of cardiac toxicity
      and patterns of maintenance strategies were recorded. RESULTS: The response
      rates, progression-free survival and overall survival in patients with metastatic
      esophagogastric cancer treated with trastuzumab and different chemotherapeutic
      regimens compared well with the data published in the TOGA trial. No unexpected
      toxicity occurred. Different strategies were used for therapy de-escalation.
      CONCLUSION: Trastuzumab-based therapy is effective in combination with several
      chemotherapeutic regimens with a safe toxicity pattern. The optimal maintenance
      strategy remains to be defined.

PMID- 25076232
TI  - Management of oral anticancer drugs: feasibility and patient approval of a
      specific monitoring program.
AB  - BACKGROUND: Oral anticancer drugs are an attractive treatment option, even if
      patient-focused education and specific nursing staff are needed to support home
      care intervention. Our aim was to assess the feasibility of a nurse monitoring
      program for patients taking oral chemotherapy, and to evaluate the patients'
      approval of the program. METHODS: At the beginning of oral chemotherapy
      treatment, outpatients completed a specific form so that we could assess their
      comprehension of the information related to therapy. Nurses gave patients a diary
      to record drug intake and toxicity at home, and phone calls were planned to
      evaluate toxicity or modification of the treatment plan during the first and
      second cycles of therapy. Finally, patients were requested to complete a specific
      form to express their level of agreement with the program. RESULTS: Eighty-one
      patients were included in the analysis. Nurse intervention at the beginning of
      therapy resulted in an increased proportion of patients having received correct
      information related to treatment, with a level of confidence rising to more than
      90% for all items considered. One hundred ninety-one of 243 planned phone calls
      were made, corresponding to 78.6% of the planned activity. The diary proved a
      valid tool for patients and 144 of 153 diaries were completed at home (94%). Only
      5 patients (6%) had unplanned hospital admission for toxicity, probably because
      of early intervention by nursing staff. Only 2 out of 63 patients expressed a
      negative opinion, while the remaining patients expressed their approval of the
      program. CONCLUSION: Our model proved practicable and accepted by patients, thus
      supporting the role of nurse intervention in training and monitoring patients
      receiving oral chemotherapy.

PMID- 25076233
TI  - Somatostatin analogs and disease control in castration-resistant prostate cancer:
      different biological behavior? Case series and review of the literature.
AB  - AIMS AND BACKGROUND: Castration-resistant prostate cancer is a recent biological
      behavior where disease can elude androgen deprivation therapy (ADT). Several
      pathways have been described, including neuroendocrine dedifferentiation.
      Patients with neuroendocrine dedifferentiation show an increase in chromogranin A
      (CgA) along with a PSA increase. Our aim was to evaluate the response of patients
      with castration-resistant prostate cancer and high CgA serum levels after
      treatment with inhibitors of neuroendocrine cells (somatostatin analogs) in
      combination with ADT. METHODS: From January 2009 to April 2011, 10 patients with
      castration-resistant prostate cancer and rising PSA levels along with a CgA
      increase were evaluated. The therapy was based on somatostatin analogs and LHRH
      anologs. Total PSA and CgA were measured every 2 months. RESULTS: In 9 of the 10
      patients, a reduction of the values of pre-treatment CgA was detected, while a
      reduction of PSA was found in 8 patients. No grade 2 or higher toxicity was
      recorded. Only 3 patients had grade 1 gastrointestinal toxicity. Time to
      progression was 13 months. CONCLUSION: Therapy with somatostatin analogs could
      increase the therapeutic window of ADT with a low toxicity profile in a
      subpopulation of patients with castration-resistant prostate cancer who
      experience a rise in CgA due to neuroendocrine regulation.

PMID- 25076234
TI  - Predictive parameters for internal mammary node drainage in patients with early
      breast cancer.
AB  - INTRODUCTION: Breast cancer treatment currently represents one of the biggest
      challenges in clinical oncology. The gold standard for axillary lymph node
      management is to perform sentinel node biopsy to avoid axillary dissection and
      its sequelae. The detection of radiocolloid flow outside the axillary nodes is a
      diagnostic and therapeutic challenge. METHODS: A database search at the
      Department of Oncology of Palacky University, Olomouc, Czech Republic, identified
      127 patients who underwent breast cancer resection with a sentinel node procedure
      and had radiocolloid flow into the internal mammary nodes. Sentinel node
      lymphoscintigraphy was performed after intraparenchymal injection. Clinical and
      pathological data were collected to identify possible risk factors. RESULTS: Ten
      clinical and pathological parameters including age, tumor histology, axillary
      lymph node status, estrogen receptor expression, progesterone receptor
      expression, tumor grade, Ki-67 expression, Her-2 status, tumor size and tumor
      location were analyzed with regard to internal mammary node drainage. A cohort of
      127 patients with detected drainage into the internal mammary nodes was compared
      with 135 patients without such drainage. Six significant risk factors, including
      age <50 years ( P <0.0313), tumor location in central and inner quadrants (P
      <0.012), larger tumor size (P <0.017), positive Her-2 status (P <0.025),
      progesterone receptor expression (P <10-4) and axillary lymph node involvement (P
      <0.01) were found to predict radiocolloid flow into the internal mammary nodes.
      CONCLUSION: Six parameters (patient age, tumor location, hormone receptor status,
      tumor size, Her-2 status and axillary lymph node status) should be considered in
      the management of breast cancer patients and help in the selection of patients
      for locoregional procedures encompassing the internal mammary nodes.

PMID- 25076235
TI  - Thulium laser versus staplers for anatomic pulmonary resections with incomplete
      fissures: negative results of a randomized trial.
AB  - AIMS: This randomized trial evaluated the feasibility and safety of thulium 2010
      nm laser to perform anatomic lung resections in patients with incomplete
      fissures, as compared to mechanical staplers with or without sealants. STUDY
      DESIGN: Seventy-two patients scheduled for segmentectomy or lobectomy were
      enrolled. After intraoperative confirmation of the extent of resection and
      incomplete fissures (Craig type 2, 3 or 4), they were randomized and allocated to
      one of the following arms: laser resection by thulium (group A) or standard
      resection with mechanical staplers with or without sealants (group B). The
      primary endpoints of the study included analysis of intraoperative and
      postoperative course, and costs. RESULTS: Thirty-eight patients were assigned to
      group A (32 lobectomies, 6 segmentectomies) and 34 to group B (31 lobectomies, 3
      segmentectomies). No 30-day mortality was observed. Median operative times were
      145.0 minutes (group A) and 142.5 minutes (group B, P = 0.83). The median time to
      drainage removal was 5 days (group A) and 4 days (group B), while the median
      length of hospital stay was the same (7 days). Prolonged air leaks >7 days were
      observed in 12 patients of group A (32%) and 10 patients of group B (29%, P =
      0.46). Unpredictable late pneumothorax occurred in 3 patients of group A (2
      readmissions, need for 1 repeat thoracotomy). Cost analysis demonstrated an
      intraoperative advantage for group A (mean 807 +/- 212 euro) versus group B (mean
      1,047+/-276 euro, P <0.0001), but the differences in total costs could be due to
      chance (P = 0.83). CONCLUSIONS: The use of laser to complete fissures can lead to
      late pneumothorax, even in the absence of postoperative air leaks. Moreover, the
      use of laser to complete fissures did not prove to reduce overall costs. Trial
      Registration Identification Number: 41/10 (IRB00001457 - FWA00001798 -
      IORG0001063).

PMID- 25076236
TI  - Comparison of acute and subacute genitourinary and gastrointestinal adverse
      events of radiotherapy for prostate cancer using intensity-modulated radiation
      therapy, three-dimensional conformal radiation therapy, permanent implant
      brachytherapy and high-dose-rate brachytherapy.
AB  - AIMS AND BACKGROUND: To examine acute and subacute urinary and rectal toxicity in
      patients with localized prostate cancer monotherapeutically treated with the
      following four radiotherapeutic techniques: intensity-modulated radiation
      therapy, three-dimensional conformal radiation therapy, low-dose-rate permanent
      implant brachytherapy using I-125 seeds, and high-dose-rate brachytherapy.
      METHODS: One hundred and fifty-six patients with localized prostate cancer were
      distributed as follows: 57 underwent intensity-modulated radiation therapy, 35
      underwent three-dimensional conformal radiation therapy, 37 underwent I-125
      implant, and 27 underwent high-dose-rate brachytherapy. The prescribed doses were
      70-74 Gy/35-37 fractions, 70 Gy/35 fractions, 145 Gy, and 45.5 Gy/7 fraction/4
      days for intensity-modulated radiation therapy, three-dimensional conformal
      radiation therapy, I-125 implant, and high-dose-rate brachytherapy, respectively.
      Toxicities (<=6 months) were retrospectively evaluated using the Common
      Terminology Criteria for Adverse Events version 4.03. RESULTS: The frequency of
      grade 1 or 2 urinary toxicities using three-dimensional conformal radiation
      therapy (33/35, 94%) was significantly higher than that with high-dose-rate
      brachytherapy (18/27, 67%) or intensity-modulated radiation therapy (37/57, 65%)
      (P <0.05). The frequency of grade 1 or 2 urinary toxicities using I-125 implant
      was 31/37, 84%. The frequency of grade 1 or 2 gastrointestinal toxicities using
      three-dimensional conformal radiation therapy (17/35, 49%) was significantly
      higher than that using I-125 implant (4/37, 11%) or high-dose-rate brachytherapy
      (0/27, 0%) (P <0.05). Using intensity-modulated radiation therapy, the frequency
      of grade 1 or 2 gastrointestinal toxicities was 18/57 (32%), which was
      significantly higher than that using high-dose-rate brachytherapy (0/27, 0%) (P
      <0.05). Grade 3 or greater adverse events were not observed. CONCLUSIONS: Acute
      and subacute genitourinary toxicities were observed more frequently after three
      dimensional conformal radiation therapy than after high-dose-rate brachytherapy
      or intensity-modulated radiation therapy. Acute and subacute gastrointestinal
      toxicities were seen more often after three-dimensional conformal radiation
      therapy than after brachytherapy (I-125 implant or high-dose-rate brachytherapy).

PMID- 25076237
TI  - Three-dimensional conformal radiotherapy, static intensity-modulated and helical
      intensity-modulated radiotherapy in glioblastoma. Dosimetric comparison in
      patients with overlap between target volumes and organs at risk.
AB  - AIMS AND BACKGROUND: Radiotherapy is the standard treatment of glioblastoma.
      Three-dimensional conformal radiotherapy is the standard technique to treat
      glioblastoma. Intensity-modulated radiotherapy and helical intensity-modulated
      radiotherapy (tomotherapy) are becoming widely used. The present study compared
      three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and
      tomotherapy in terms of target coverage and preservation of organs at risk.
      METHODS: Ten patients treated with three-dimensional conformal radiotherapy, with
      a target volume close to or superimposed to the organs at risk, were
      retrospectively selected. The plans were re-planned with step-and-shoot 3/5
      fields intensity-modulated radiotherapy and tomotherapy. Target coverage and
      sparing of organs at risk were statistically compared. RESULTS: Mean planning
      target volume V95% improved with sophisticated techniques (87.2%, 93.2%, 97.6%
      with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy
      and tomotherapy, respectively). The comparison of three-dimensional conformal
      radiotherapy and intensity-modulated radiotherapy did not show significant
      differences, whereas differences were significant when three-dimensional
      conformal radiotherapy and tomotherapy as well as intensity-modulated
      radiotherapy and tomotherapy were compared. Mean planning target volume/clinical
      target volume D99-D98-D95 were not different between three-dimensional conformal
      radiotherapy and intensity-modulated radiotherapy, but they were different
      between tomotherapy and three-dimensional conformal radiotherapy and intensity
      modulated radiotherapy, with better clinical target volume/and planning target
      volume coverage with the tomotherapy plans. Brain D33/66 were 31.1/11.8 Gy,
      37.5/18.3 Gy and 28.5/14.7 Gy with three-dimensional conformal radiotherapy,
      intensity-modulated radiotherapy and tomotherapy, respectively. Mean brainstem,
      optic nerves and chiasma Dmax were always within the defined constraints. The
      homogeneity index improved with intensity-modulated radiotherapy/tomotherapy
      compared to three-dimensional conformal radiotherapy. Tomotherapy was better than
      intensity-modulated radiotherapy in all patients. CONCLUSIONS: In this selected
      group of patients, a significant dosimetric advantage was evident for tomotherapy
      compared with three-dimensional conformal radiotherapy and intensity-modulated
      radiotherapy. Significant advantages were evident in terms of panning target
      volume coverage (V95), D99, D98 and D95. The clinical significance of the results
      should be defined.

PMID- 25076238
TI  - Salvage stereotactic re-irradiation with CyberKnife for locally recurrent head
      and neck cancer: a single center experience.
AB  - AIMS AND BACKGROUND: We report the toxicity and preliminary clinical outcome in
      patients affected by locally recurrent head and neck cancer treated with
      stereotactic re-irradiation. METHODS: Between February 2012 and August 2013, 17
      patients were treated with CyberKnife as stereotactic re-irradiation for locally
      recurrent head and neck cancer. All patients had previously received a full dose
      radiation treatment with radical intent, with a median total dose of 66 Gy
      (range, 50-70) delivered with standard fractionation. The median interval between
      the primary radiotherapy and re-irradiation was 24 months (range, 10-168).
      RESULTS: All patients completed the prescribed treatment, which was delivered in
      5 fractions. The median tumor dose administered was 30 Gy (range, 25-35)
      prescribed to the 80% isodose line. Treatment sites were as follows: neck lymph
      nodes in 5 patients, paranasal sinuses in 5, oropharynx in 2, nasopharynx, and
      larynx, oral cavity, nasal fossa and parotid gland each in 1 patient. The median
      target volume treated was 58.7 cm3 (range, 8.5-211.3). Sixteen patients (94%)
      were evaluated for response. At a median follow-up of 7.5 months (range, 2-17), 4
      patients achieved complete response (25%), 5 had partial response (31%) and 7
      showed stable disease (44%). No patient showed in-field progression after re
      irradiation. Grade 3 acute toxicity was noted in one patient only; no late side
      effect was observed during the follow-up. CONCLUSIONS: Stereotactic re
      irradiation with CyberKnife is an appealing non-surgical salvage treatment for
      selected patients with local-regionally recurrent head and neck cancer.

PMID- 25076239
TI  - Practice patterns for oropharyngeal cancer in radiation oncology centers of
      Turkey.
AB  - AIMS AND BACKGROUND: The aim of the study was to review the current clinical
      practices of radiation oncologists involved in the treatment of oropharyngeal
      cancer. METHODS AND STUDY DESIGN: The daily practices of radiation oncology
      centers for patients diagnosed with oropharyngeal cancer in 2010 were evaluated
      by a two-part questionnaire that separately assessed the information of the
      participating center and the charts of the treated patients. RESULTS: A total of
      22 centers participated in the study, and 105 oropharyngeal cancer patients
      reported for our review. The use of positron emission tomography was a common
      practice in staging and radiotherapy planning. Multidisciplinary head and neck
      cancer clinics were available in 14 (64%) centers and were absent in 8 centers.
      Thirty-six of the 105 patients were not evaluated by a multidisciplinary clinic
      before the initiation of therapy, and adjuvant radiotherapy administration was
      found to be higher in this group. Percutaneous endoscopic gastrostomy tube
      placement was not a routine practice in any of the centers. Seventy-five patients
      received chemotherapy - 46 concurrently with radiotherapy and 29 as induction
      chemotherapy. Two centers administered conventional radiotherapy alone, 20
      centers conformal radiotherapy, and 7 centers were able to provide intensity
      modulated radiotherapy. CONCLUSIONS: Across all the centers there were small
      differences in the pretreatment evaluation of patients with oropharyngeal cancer.
      The greatest difference was in the technical delivery of radiation, with most of
      the centers using conformal radiotherapy despite the increasing availability of
      intensity-modulated radiotherapy. The use of chemotherapy has more readily
      adopted the current international standards in the treatment of oropharyngeal
      cancer.

PMID- 25076240
TI  - Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the
      impact of thoracic and brain irradiation on survival.
AB  - AIMS AND BACKGROUND: Small cell lung cancer is an aggressive histologic subtype
      of lung cancer in which the role of chemotherapy and radiotherapy has been well
      established in limited-stage disease. We retrospectively reviewed a series of
      limited-stage small cell lung cancers treated with chemotherapy and thoracic and
      brain radiotherapy. METHODS AND STUDY DESIGN: A total of 124 patients affected by
      limited-stage small cell lung cancer has been treated over 10 years in our
      Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy
      treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients
      (70.9%) underwent an association of a platinum-derived drug (cisplatinum or
      carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all
      patients with histologically proven complete response to primary radio
      chemotherapy. RESULTS: With a mean follow-up of 2.2 years, complete response was
      obtained in 50.8% of cases. We found a significant difference between different
      radio-chemotherapy association approaches (P = 0.007): percentages of overall
      survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and
      sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to
      influence overall survival (P = 0.21) or disease-free survival for local relapse
      (P = 0.34). CONCLUSIONS: Concomitant radio-chemotherapy is the best approach
      according to our experience. Our results show a benefit of prophylactic cranial
      irradiation in distant metastasis-free survival.

PMID- 25076241
TI  - Computed tomography-guided percutaneous permanent iodine-125 implantation for
      patients with malignant osseous tumors.
AB  - AIMS AND BACKGROUND: In the present study, we evaluated the value of computed
      tomography-guided 125I implantation for malignant osseous tumors. METHODS: Under
      computed tomography guidance, 125I seeds were implanted into malignant osseous
      tumors of 19 patients. The curative effect was evaluated according to the degree
      of ostealgia relief and the changes in radiological images. RESULTS: The 125I
      seeds were implanted successfully in all 19 cases. No complication was observed.
      Pain relief was obtained in 17 of the 19 malignant osseous tumor patients after
      implantation, and the effective rate was 89.5%. Follow-up computed tomography
      reexamination at 1, 2 and 6 months demonstrated that of the 25 lesions in 19
      cases, obvious relief was obtained in 2, partial relief in 15, a slight decrease
      in 7, and a progressive decrease in 1. The response rate was 68%. CONCLUSIONS:
      Computed tomography-guided 125I implantation is a safe, effective and feasible
      method in the treatment of patients with malignant osseous tumors.

PMID- 25076242
TI  - Management of patients with >=4 brain metastases using stereotactic radiosurgery
      boost after whole brain irradiation.
AB  - AIMS AND BACKGROUND: Brain metastases are a prevalent consequence of systemic
      cancer, and patients suffering from brain metastases usually present with
      multiple metastatic lesions. An overwhelming majority of the available literature
      assessing the role of stereotactic radiosurgery in brain metastasis management
      includes patients with up to 4 metastases. Given the significant benefit of
      stereotactic radiosurgery for the treatment of 1 to 3 brain metastases, we
      evaluated the use of stereotactic radiosurgery boost after whole brain
      irradiation in the management of patients with >=4 brain metastases. METHODS: In
      this retrospective analysis, outcomes of 50 patients who underwent linear
      accelerator-based stereotactic radiosurgery boost within 4 to 6 weeks of whole
      brain irradiation for >=4 brain metastases were assessed in terms of local
      control, overall survival, primary involved organ, recursive partitioning
      analysis class and Karnofsky performance status at the time of stereotactic
      radiosurgery, number of lesions, age, status of the primary cancer (controlled vs
      uncontrolled), presence of extracranial disease and toxicity. RESULTS: Fifty
      patients with >=4 brain metastases were treated using linear accelerator-based
      stereotactic radiosurgery boost after whole brain irradiation between April 1998
      and April 2013. Mean and median number of intracranial lesions was 6.02 and 6,
      respectively. Median lesion volume was 10.9 cc (range, 0.05-32.6). Median
      survival time after radiosurgery was 10.1 months (range, 1-25). Status of the
      primary cancer (controlled vs uncontrolled), recursive partitioning analysis
      class, Karnofsky performance status, and extracranial metastasis showed
      statistically significant correlations with overall survival (P <0.001).
      Treatment-related side effects after stereotactic radiosurgery included temporary
      edema (n = 14, 28%), hemiparesis (n = 1, 2%), seizure (n = 1, 2%),
      leukoencephalopathy (n = 2, 4%), and radiation necrosis (n = 6, 12%).
      CONCLUSIONS: Linear accelerator-based stereotactic radiosurgery boost within 4 to
      6 weeks after whole brain irradiation proved to be an efficacious and well
      tolerated treatment strategy for the management of patients with >=4 brain
      metastases in our study.

PMID- 25076243
TI  - A survey of Italian radiation oncologists: job satisfaction and burnout.
AB  - AIMS AND BACKGROUND: Job satisfaction and burnout can greatly affect the quality
      of life of professionals involved in the medical field and can also have an
      impact on many aspects of the work. The aim of the present study was to
      investigate professional history, professional satisfaction and burnout in
      Italian radiation oncologists. METHODS AND STUDY DESIGN: Members of the Italian
      Association of Radiation Oncology (AIRO) were asked to complete a questionnaire
      composed of three sections including personal and professional information, the
      Job Satisfaction Scale (JSS) and the Link Burnout Questionnaire (LBQ). RESULTS:
      The 167 participants were prevalently males working in public hospitals. About
      half of participants were staff physicians, mainly with no other specialty.
      Concerning the JSS, most respondents were moderately to extremely satisfied with
      their job. With regard to the LBQ, instead, we found critical results in the four
      investigated dimensions (psychophysical exhaustion, relation deterioration,
      professional failure and disillusion). CONCLUSIONS: This study suggests that
      Italian radiation oncologists have good medical background and education levels
      with a deep understanding of working in a clinical discipline. Organizational
      factors and the work climate are the main determinants of the satisfaction level
      and burnout is limited to a small percentage of professionals. The identification
      of specific profiles for professionals with higher levels of burnout or poorer
      job satisfaction may allow the delivery of targeted prevention or support
      interventions with the aim of improving workers' quality of life, satisfaction
      and perception of effectiveness.

PMID- 25076244
TI  - BRAF mutation analysis is a valid tool to implement in Lynch syndrome diagnosis
      in patients classified according to the Bethesda guidelines.
AB  - AIMS AND BACKGROUND: Lynch syndrome (LS) is clinically defined by the Amsterdam
      criteria (AC) and by germline mutations in mismatch-repair (MMR) genes leading to
      microsatellite instability (MSI) at the molecular level. Patients who do not
      fulfil AC are considered suspected-Lynch according to the less stringent Bethesda
      guidelines (BG) and should be tested for MSI and MMR germline mutations. BRAF
      mutations have been proposed as a marker to exclude LS because they are generally
      absent in LS patients and present in sporadic colorectal cancer (sCRC) with MSI
      due to promoter hypermethylation of the MLH1 gene. Our aim was to verify whether
      BRAF mutations may improve the criteria to select patients for germline MMR
      mutation assessment. MATERIAL AND METHODS: We analyzed 303 formalin-fixed
      paraffin-embedded CRC samples including 174 sCRC, 28 patients fulfilling AC, and
      101 suspected-Lynch patients fulfilling BG. We analyzed MSI and BRAF mutations in
      all CRC samples. MLH1, MSH2 and MSH6 germline mutations were investigated in MSI
      patients fulfilling AC or BG. RESULTS: sCRC samples showed MSI in 20/174 (11%)
      cases. BRAF mutations were detected in 10/174 (6%) sCRC cases and were
      significantly correlated with MSI (P = 0.002). MSI was observed in 24/28 (86%)
      Amsterdam cases which were BRAF wild-type. MMR gene mutation was detected in
      22/26 (85%) AC cases, all showing MSI. Suspected-Lynch cases carried MSI in
      41/101 (40%) and BRAF mutations in 7/101 (7%) cases. MMR gene mutation was
      detected in 13/28 (46%) evaluable MSI patients of this group and only in cases
      characterized by a wild-type BRAF gene. CONCLUSIONS: The prevalence of BRAF
      mutations in CRC patients is not high but extremely correlated with MSI and risk
      categories as BG, whereas they are absent in LS patients. BRAF mutation detection
      can reduce the need for MMR gene analysis in a small (but not negligible)
      proportion of MSI patients (7%), with a positive impact on the financial and
      psychological costs of unnecessary tests.

PMID- 25076245
TI  - Expression of CD44v3, erythropoietin and VEGF-C in gastric adenocarcinomas:
      correlations with clinicopathological features.
AB  - AIMS: To investigate the expression of CD44v3 and vascular endothelial growth
      factor C (VEGF-C) in gastric adenocarcinoma and the correlation with
      erythropoietin (EPO) and clinicopathological features. METHODS: The expression of
      CD44v3, VEGF-C and EPO was evaluated by immunohistochemical staining in 169
      gastric adenocarcinomas. The correlations between these parameters and patients'
      clinicopathological features were analyzed statistically. RESULTS: CD44v3 and
      VEGF-C were positive in 50 (29.6%) and 82 (48.5%) patients, respectively. High
      CD44v3 expression was associated with poor cellular differentiation, extensive
      lymph node metastasis and advanced stage of gastric adenocarcinoma (P <0.05).
      High VEGF-C expression was significantly correlated with Lauren type, extensive
      lymph node metastasis and advanced stage of gastric adenocarcinoma (P <0.05).
      Univariate analysis of survival demonstrated that patients with a strong CD44v3
      immunoreaction had a significantly worse overall survival compared with patients
      showing a weak CD44v3 immunoreaction (log-rank test: P = 0.0449). The mean
      survival time of patients with low CD44v3 expression was 30.6 months, which was
      much longer than the 21.6 months in patients with high expression. In addition, a
      strong association between immunohistochemical expression of CD44v3 and EPO was
      noted. CONCLUSION: Increased expression of CD44v3 and VEGF-C may play a
      significant role in the carcinogenesis and progression of gastric adenocarcinoma.
      High CD44v3 expression may be a predictor of poor prognosis in gastric
      adenocarcinoma patients. We infer that some mechanisms may exist in regulating
      the expression of CD44v3 and EPO.

PMID- 25076246
TI  - Low expression of excision repair cross-complementation group-1 protein predicts
      better outcome in patients with locally advanced nasopharyngeal cancer treated
      with concurrent chemoradiotherapy.
AB  - AIMS AND BACKGROUND: Cisplatin-based concurrent chemoradiotherapy is the standard
      treatment of locally advanced nasopharyngeal cancer. We conducted this study to
      assess the value of excision repair cross-complementation group 1 (ERCC1) protein
      expression in predicting the clinical outcome of patients with locally advanced
      nasopharyngeal cancer who were treated with cisplatin-based concurrent
      chemoradiotherapy. METHODS AND STUDY DESIGN: We employed immunohistochemical
      analysis to determine the expression of ERCC1 protein among 66 patients with
      locally advanced nasopharyngeal cancer who were treated with concurrent
      chemoradiotherapy. The relationship of ERCC1 expression to clinical outcome was
      analyzed. RESULTS: There were no statistically significant differences in gender,
      age, T stage, N stage, clinical staging and treatment method between the high
      ERCC1 expression and low ERCC1 expression groups. Fifty-eight patients (87.88%)
      had a complete response and 8 (12.12%) a partial response. Of the 34 patients
      with high ERCC1 expression, 10 (29.41%) relapsed, compared with 4 of 32 (12.5%)
      patients with low ERCC1 expression (P = 0.041). The 5-year overall survival rate
      was 58.82% in patients with high ERCC1 expression and 84.37% in patients with low
      ERCC1 expression (P = 0.022). Multivariate analysis showed that low expression of
      ERCC1 was a significant independent prognostic factor for better overall survival
      (P = 0.026). CONCLUSIONS: Low ERCC1 expression is associated with prolonged
      survival in patients with locally advanced nasopharyngeal cancer receiving
      cisplatin-based concurrent chemoradiotherapy. ERCC1 expression may become a
      molecular marker in predicting the clinical outcome of these patients.

PMID- 25076247
TI  - Relationship of MDA plasma concentrations to long-term survival of breast cancer
      patients.
AB  - AIMS AND BACKGROUND: Malondialdehyde (MDA) is a product of polyunsaturated fatty
      acid oxidation. Changes in MDA concentrations have been found in patients with
      various types of cancer. The aim of this study was to analyze the relationship of
      MDA plasma concentrations to the long-term survival of patients with breast
      cancer. METHODS AND STUDY DESIGN: We conducted a retrospective study which
      included 106 patients at various disease stages (I - n = 2; II - n = 30; III - n
      = 51; IV - n = 23). Plasma MDA concentrations were measured at the time of
      diagnosis. Study participants were divided into groups according to age (<55
      years vs >=55 years), disease stage, and MDA concentration (<9 mmol/L vs >=9
      mmol/L). Survival rates between groups were compared using the Kaplan-Meier
      method. RESULTS: We found that higher MDA concentrations were associated with
      lower survival rates in stage I and II breast cancer. No significant association
      was found in patients with stage III and IV disease. Multivariate analysis showed
      that the MDA level was the only independent prognostic factor for patient
      survival in the total study group (hazard ratio 1.57, P = 0.03). CONCLUSION: MDA
      can be used as a prognostic factor in early stages of breast cancer.

PMID- 25076248
TI  - Gene expression analysis of lung adenocarcinoma and matched adjacent non-tumor
      lung tissue.
AB  - AIMS AND BACKGROUND: The aim of this study was to find disease-associated genes
      and gene functions in lung adenocarcinoma and matched adjacent non-tumor lung
      tissues with DNA microarray. METHODS: We downloaded the gene expression profile
      GSE32863 from the Gene Expression Omnibus database including 58 lung
      adenocarcinoma and 58 adjacent non-tumor lung tissue samples. Data were
      preprocessed and the differentially expressed genes (DEGs) were identified using
      packages in the R computing language. The selected DEGs were further analyzed
      with bioinformatics methods. After the coexpression network of DEGs was
      constructed by STRING (Search Tool for the Retrieval of Interacting
      Genes/Proteins), we analyzed gene functions with DAVID (The Database for
      Annotation, Visualization and Integrated Discovery) and WebGestalt (WEB-based
      Gene Set Analysis Toolkit). RESULTS: A total of 1429 genes were filtered as DEGs,
      including 873 downregulated genes and 556 upregulated genes, and the DEGs
      including CDC45, CCNB2, CDC20, MCM2, PTTG1, MCM4 and FEN1 were most significantly
      related to cell cycle and DNA replication. CONCLUSION: The discovery of featured
      genes which were significantly related to cell cycle and DNA replication has
      potential for use in the clinic for the diagnosis of lung adenocarcinoma in the
      future. However, further experiments will be needed to confirm our result.

PMID- 25076249
TI  - Cancer rehabilitation services: an Italian population-based cohort study.
AB  - AIMS AND BACKGROUND: In Italy more than 55% of cancer patients live for more than
      5 years after diagnosis, sometimes with several cancer-related sequelae. For this
      reason rehabilitation must offer not only physical interventions but also
      psychological, clinical, social and nutritional support. The CAREMORE pilot study
      was designed to assess whether cancer registries could serve to collect
      information on rehabilitation services, to describe and quantify the services
      provided by the National Health Service, and to examine the allocation of
      rehabilitation services to cancer patients. METHODS AND STUDY DESIGN: This was a
      pilot population-based cohort study. A sample of 1200 patients was identified
      from the databases of the Varese, Genoa, Reggio Emilia, Sassari and Ragusa cancer
      registries, all diagnosed in 2002 and followed for 5 years. For 4 cancer sites a
      list of rehabilitation items to be collected was drafted by a joint community of
      researchers and voluntary associations, with variables regarding rehabilitation
      data and follow-up. Data were analyzed by groups of patients, vital status, sex,
      and age. RESULTS: This pilot study suggested it is useful to collect information
      on several rehabilitation services: disability benefits, home care, aids and
      other support; it was not possible to collect reliable information on nutritional
      and psychological rehabilitation. In all, 36% of the sample applied for
      disability benefits, but with important differences between cancer sites. Eleven
      percent of the sample obtained home care, with no substantial differences between
      cancer sites, and 16% received at least one aid, with percentages varying from
      27% for rectal cancer to 8% for lymphoma patients. CONCLUSIONS: The pilot study
      indicated that cancer registries could collect information on rehabilitation
      services. In the future it would be interesting to expand the roles of these
      registries to factors that influence quality of life, taking into account the
      possibility of collecting more information by actually interviewing patients.

PMID- 25076250
TI  - Upregulation of ID2 antagonizes arsenic trioxide-induced antitumor effects in
      cancer cells.
AB  - AIMS AND BACKGROUND: Arsenic trioxide (ATO) strongly induces apoptosis and
      differentiation in acute promyelocytic leukemia, and induces cell cycle arrest in
      most solid tumors. Although many signaling pathways are involved in its antitumor
      mechanism, a detailed investigation of the transforming growth factor beta-bone
      morphogenetic protein signaling pathway has not been performed. METHODS AND STUDY
      DESIGN: A microarray containing 113 genes associated with the pathway was used to
      screen important molecules that participate in the antitumor effects of ATO. The
      expression levels of the inhibitors of DNA binding-2 (ID2) in 4 different types
      of cancer cells were determined by quantitative reverse transcription PCR and
      Western blotting. Human esophageal squamous cell carcinoma cell line Eca109 and
      pancreatic carcinoma cell line BxPC3 cells were transfected with siRNAs targeting
      ID2 and scrambled control siRNA. Cell proliferation was evaluated by methyl
      thiazolyl tetrazolium assay. RESULTS: Eighteen upregulated and 12 downregulated
      genes were identified. After verification at the transcriptional and
      translational levels in 4 different cancer cells, ID2 was identified as an ATO
      antitumor-associated protein. In addition, specific silencing of ID2 could
      enhance ATO-induced cell proliferation inhibition in cancer cells. CONCLUSIONS: A
      combination of ATO and ID2-targeted agents may have considerable therapeutic
      benefits in cancers.

PMID- 25076251
TI  - Updates from the 2013 Society for Neuro-Oncology annual and World Federation for
      Neuro-Oncology quadrennial meeting.
AB  - We present an overview of a number of key clinical studies in infiltrating
      gliomas presented at the 2013 Society for Neuro-Oncology and World Federation of
      Neuro-Oncology joint meeting. This review focuses on efficacy results, including
      quality of life studies, from larger clinical trials in both high- and low-grade
      infiltrating gliomas. 

PMID- 25076252
TI  - Prolonged disease stability with trabectedin in two monorenal patients with
      retroperitoneal sarcoma.
AB  - Soft tissue sarcomas constitute a heterogeneous group of tumors of mesenchymal
      origin: at present, more than 50 separate histological subtypes of soft tissue
      sarcoma have been listed. Although there have been advances in the understanding
      of these tumors and their treatment over the past few years, there is still a
      lack of consensus on the standard of care, and new therapeutic options are
      eagerly awaited. Trabectedin has been approved for the treatment of patients with
      advanced soft tissue sarcomas after failure of anthracyclines and ifosfamide.
      However, the effectiveness and tolerability of this agent in retroperitoneal soft
      tissue sarcomas have been poorly characterized. Here we report the cases of two
      monorenal patients with a retroperitoneal sarcoma who achieved prolonged
      stabilization of disease with trabectedin. Trabectedin-associated toxicities were
      generally mild and were successfully managed by supportive care. Of note, the
      patients did not experience clinically relevant myelosuppression, which is
      currently considered the limiting toxicity of trabectedin. 

PMID- 25076253
TI  - Lapatinib and platinum-based chemotherapy ameliorate breast cancer with choroidal
      metastasis and restore visual acuity.
AB  - Involvement of the central nervous system in metastatic breast cancer is a
      particularly dismal occurrence because of its effects on mortality and quality of
      life. Development of choroidal metastasis in a breast cancer patient indicates
      poor prognosis and has become the major life-limiting problem. Various treatment
      modalities for choroidal metastasis have been applied with different efficacy.
      Here we describe a patient with HER2-overexpressing breast cancer and limited
      choroidal metastasis who responded to an HER2 tyrosine kinase inhibitor after
      failure of radiotherapy and chemotherapy. Her visual acuity was completely and
      durably restored after the targeted therapy. This case provides a unique
      treatment experience of breast cancer with choroidal metastasis.

PMID- 25076254
TI  - Retreatment with erlotinib of a patient with metastatic NSCLC harboring EGFR
      mutation: a case report.
AB  - Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
      used for the treatment of advanced stage non-small cell lung cancer (NSCLC).
      Clinical trials have shown high efficacy of erlotinib, particularly in patients
      harboring activating mutations in the EGFR gene. Here we describe the case of a
      42-year-old female light smoker diagnosed with EGFR mutation-positive
      adenocarcinoma of the left lung with pleural metastases, pleural effusion and
      metastases to the thoracic vertebrae (stage IV, T4NXM1). Although the patient
      developed resistance to erlotinib in the first line, she achieved disease
      stabilization lasting for 13 months as a response to erlotinib retreatment after
      6 cycles of second-line chemotherapy. In conclusion, retreatment with erlotinib
      in our patient was effective. Therefore it should be considered as a good
      treatment option for patients with NSCLC harboring EGFR mutation.

PMID- 25076255
TI  - Cerebellar glioblastoma multiforme in an adult woman.
AB  - AIMS AND BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent primary
      central nervous system malignancy in adults, accounting for 50% of all primary
      intracranial malignancies. GBM mostly arises within the cerebral hemispheres and
      frequently affects patients in the fifth and sixth decades of life. Conversely,
      primary cerebellar GBM is a rather infrequent occurrence in the adult population,
      accounting for 1%-2.2% of all GBMs. Here we report a case of cerebellar GBM in an
      adult woman and provide an extensive review of the literature. METHODS: A 42-year
      old woman was referred to our hospital for occipital constrictive headache,
      dizziness and gait disturbance. Multimodality imaging including computed
      tomography and magnetic resonance imaging (MRI) showed a right cerebellar mass.
      Gross total resection was performed. Histological examination showed grade IV GBM
      according to the World Health Organization classification, with a synchronous
      component of low-grade glioma. Immunohistochemistry showed positivity for p53 and
      negativity for epidermal growth factor receptor (EGFR). After surgical tumor
      excision, the patient underwent adjuvant radiation to the posterior fossa with an
      intensity-modulated approach for a total dose of 60 Gy in 30 fractions. In
      addition, she received concurrent and adjuvant chemotherapy with temozolomide.
      RESULTS: Treatment was well tolerated, with mild acute toxicity. There was no
      evidence of recurrence on brain and spinal gadolinium-enhanced MRI scans 4, 8 and
      12 months after primary surgery. No late side effects were recorded. CONCLUSION:
      Our patient had several immunohistochemical characteristics of secondary
      glioblastoma such as p53 positivity, EGFR negativity and the presence of a low
      grade glioma component. Intensity-modulated radiation therapy allowed us to
      safely deliver full-dose radiation with sparing of critical structures.

PMID- 25076256
TI  - Long-term complete response in a patient with liver metastases from breast cancer
      treated with metronomic chemotherapy.
AB  - BACKGROUND: Preclinical studies have shown that several chemotherapeutic agents
      at low doses may affect the vascular system. Here we report the case of a patient
      with long-term cancer control by metronomic chemotherapy. CASE PRESENTATION: A 62
      year-old woman with breast cancer underwent a left mastectomy in July 2007. For a
      liver metastasis she was given first-line chemotherapy with doxorubicin plus
      paclitaxel every 21 days. A CT scan after the sixth cycle showed a partial
      response. It was decided to stop the treatment with doxorubicin and paclitaxel,
      and start metronomic therapy with cyclophosphamide 50 mg daily orally and
      methotrexate 2.5 mg twice daily, 2 days a week. After 6 months of this
      maintenance treatment, CT scan showed a complete response. We examined the
      expression of vascular endothelial growth factor receptor 2 (VEGFR2) in
      histological sections of the primary tumor of our patient, finding evidence of
      overexpression of the receptor. The metronomic treatment is still ongoing, and
      after 60 months the patient maintains a complete response. CONCLUSION: This
      clinical case highlights how suitable metronomic chemotherapy can be used as
      maintenance therapy, allowing long-term treatment with no significant toxicity.
      This case suggests that the level of VEGFR2 is predictive of best response to
      antiangiogenic therapy.

PMID- 25076257
TI  - Early and prolonged response to pazopanib in a patient with multiple metastases
      from renal cell carcinoma: a case report.
AB  - AIMS AND BACKGROUND: In recent years, targeted agents have replaced cytokine
      therapy as the standard of care for patients with metastatic renal cell
      carcinoma. METHODS AND STUDY DESIGN: We report a patient with multiple metastases
      from renal cell carcinoma treated with cytoreductive surgery and pazopanib.
      RESULTS AND CONCLUSIONS: The treatment resulted in an early and prolonged
      response, without toxicity.

PMID- 25076258
TI  - Outcomes of patients with metastatic renal cell carcinoma treated with pazopanib
      in daily clinical practice: a single institution experience.
AB  - In the last few years, many targeted agents have been introduced for the
      treatment of advanced and/or metastatic renal cell carcinoma. Such agents have
      demonstrated a prolongation of progression-free survival, but the optimal
      treatment strategy is still unclear. Many decisions of clinicians are based on
      pivotal trial results that are not always transferable to a real-world setting.
      We report a retrospective monoinstitutional experience of first-line treatment
      with pazopanib in a series of patients with metastatic renal cell carcinoma. The
      aim of the present experience was to evaluate the activity and safety of
      pazopanib in an unselected patient population extracted from clinical practice.
      Our findings suggest that efficacy and toxicity profiles of pazopanib in the real
      world population appear consistent with trial-based expectations. The preliminary
      results need to be confirmed on a larger cohort, due to the small number of
      patients evaluated. 

PMID- 25076259
TI  - Could single-high-dose radiotherapy be considered the new frontier of
      stereotactic ablative radiation therapy?

PMID- 25076260
TI  - "Green Oncology": the Italian medical oncologists' challenge to reduce the
      ecological impact of their clinical activity.
AB  - For decades Western medicine has followed a biomedical model based on linear
      thinking and an individualized, disease-oriented doctor-patient relationship.
      Today this framework must be replaced by a biopsychosocial model based on
      complexity theory and a person-oriented medical team-patient relationship, taking
      into account the psychological and social determinants of health and disease.
      However, the new model is already proving no longer adequate or appropriate, and
      current events are urging us to develop an ecological model in which the medical
      team takes into account both individual illness and population health as a whole,
      since we are all part of the biosphere. In recent years, the rising costs of
      cancer treatment have raised a serious issue of economic sustainability. As the
      population of our planet, we now need to rapidly address this issue, and everyone
      of us must try to reduce their ecological footprint, measured as CO2 production.
      Medical oncologists need to reduce the ecological footprint of their professional
      activity by lowering the consumption of economic resources and avoiding
      environmental damage as much as possible. This new paradigm is endorsed by the
      Italian College of Hospital Medical Oncology Directors (CIPOMO). A working group
      of this organization has drafted the "Green Oncology Position Paper": a proposal
      of Italian medical oncology (in accordance with international guidelines) that
      oncologists, while aiming for the same end results, make a commitment toward the
      more appropriate management of health care and the careful use of resources in
      order to protect the environment and the ecosphere during the daily exercise of
      their professional activities. 

PMID- 25076262
TI  - Self-assembly of stable oligomeric and fibrillar aggregates of Abeta peptides
      relevant to Alzheimer's disease: morphology dependent Cu/heme toxicity and
      inhibition of PROS generation.
AB  - Large and small aggregates of Abeta peptides, resembling the morphology and
      dimensions of fibrillar and oligomeric forms of Abeta respectively, relevant to
      Alzheimer's disease, are stabilized on electrodes using self-assembly. Both of
      these forms were found to bind redox active Cu and heme, resulting in active
      sites having distinctive biophysical properties. The reduced metal bound Abeta
      active sites of both the oligomeric and fibrillar forms of Abeta produce
      detrimental partially reduced oxygen species (PROS). While the larger aggregates
      of heme-Abeta produce more PROS in situ, the smaller aggregates of Cu-Abeta
      produce more PROS. 8-Hydroxy quinoline and methylene blue are inhibitors of Cu
      and heme bound Abeta respectively, and are shown to efficiently reduce PROS
      formation in the oligomeric forms. However, these inhibitors are ineffective in
      reducing the toxicities of the Cu and heme bound Abeta peptides in the fibrils,
      making them significantly more lethal than the smaller Abeta aggregates. 

PMID- 25076263
TI  - Suicidal behaviour and lipid levels in unipolar and bipolar depression.
AB  - INTRODUCTION: Evidence for a possible association between a low level of
      cholesterol and increased suicidal behaviour has accumulated in the recent 3
      decades. The present study investigates whether lipid levels can make state
      dependent markers of suicidal behaviour in Polish patients with mood disorder
      recently admitted to a psychiatric hospital owing to an acute depressive episode.
      MATERIALS AND METHODS: The study was conducted on 223 patients (73 male and 150
      female) with unipolar (n=171) and bipolar (n=52) depression. They were
      interviewed to assess any occurrence of suicidal thoughts, suicidal tendencies
      and/or suicidal attempts during the 3 months before admission. Laboratory
      measurements [total cholesterol, low density lipoprotein (LDL) cholesterol, high
      density lipoprotein (HDL) cholesterol, triglycerides and total lipids] were
      obtained within 24-72 h after hospital admission. RESULTS: Suicidal thoughts,
      tendencies, and attempts were associated with low total cholesterol, LDL
      cholesterol, and total lipids in both male and female patients, in both
      diagnostic categories. Triglycerides were significantly lower in male and female
      patients with suicidal thoughts compared with their non-suicidal counterparts. No
      association with suicidality was found with HDL cholesterol. CONCLUSIONS: The
      results of our study support a majority of research showing the association in
      depressed patients between suicidal behaviour and low levels of total and LDL
      cholesterol. In addition, the data suggest a similar association with low total
      lipids, and in some instances, with low triglycerides.

PMID- 25076264
TI  - Originality and plagiarism: a question of authorship in the academy.

PMID- 25076265
TI  - [Barriers in health care to breast cancer: perception of women].
AB  - OBJECTIVE: Identifying the barriers in the access to health care to breast cancer
      perceived by women undergoing chemotherapy. METHOD: An exploratory descriptive
      study. The sample consisted of 58 women with breast cancer receiving chemotherapy
      and registered in the public oncology ambulatory of Aracaju-Sergipe. Data
      collection was carried out between October 2011 and March 2012 by semistructured
      interviews, and data were processed using the SPSS, version 17. RESULTS: Among
      the interviewed women, 37 (63.8%) reported at least a barrier in the trajectory
      of care for breast cancer. The organizational and health services barriers were
      the most reported in the periods of investigation and treatment of breast cancer.
      CONCLUSION: In face of these findings, the barriers should be considered in
      public health policies and programs for the control of breast cancer in Sergipe.

PMID- 25076266
TI  - [Hospitalizations leading causes for maternal disorders].
AB  - Presenting the rates of obstetric admissions of women living in Parana in 2010.
      METHOD: A descriptive study in which the admission information of the hospital
      system of the Unified Health System was analyzed. Data from women aged between 10
      to 49 years available on the DATASUS website were analyzed, using percentage and
      according to primary diagnosis, age and Regional Health area. RESULTS: The Rate
      of Obstetric Complications (RtOC) was 38%, increasing with the age of women.
      Complications of labor and delivery (10.5%), and pregnancy with abortive outcome
      (9.1%) were the diagnoses with highest RtOC. The RtOC ranged between 8.4% in
      Telemaco Borba, until 62.6% in Ponta Grossa. CONCLUSION: The healthcare team
      should monitor the rates of admissions for obstetric complications as these
      indicate the quality of health care of women, mainly focused on labor, delivery
      and women of older age.

PMID- 25076267
TI  - [Hemoglobin curves during pregnancy before and after fortification of flours with
      iron].
AB  - OBJECTIVE: To assess the level of hemoglobin-Hb during pregnancy before and after
      fortification of flours with iron. METHOD: A cross-sectional study with data from
      12,119 pregnant women attended at a public prenatal from five macro regions of
      Brazil. The sample was divided into two groups: Before-fortification (birth
      before June/2004) and After-fortification (last menstruation after June/2005). Hb
      curves were compared with national and international references. Polynomial
      regression models were built, with a significance level of 5%. RESULTS: Although
      the higher levels of Hb in all gestational months after-fortification, the
      polynomial regression did not show the fortification effect (p=0.3). Curves in
      the two groups were above the references in the first trimester, with following
      decrease and stabilization at the end of pregnancy. CONCLUSION: Although the
      fortification effect was not confirmed, the study presents variation of Hb levels
      during pregnancy, which is important for assistencial practice and evaluation of
      public policies.

PMID- 25076268
TI  - [Meaning of becoming mother and son/daughter through massage].
AB  - OBJECTIVE: Revealing the experience of mothers when massaging their children to
      know the phenomenon in the context of a mother-child healthy development. METHOD:
      This is a qualitative study with a phenomenological approach carried out with 11
      women who massaged their children and answered the guiding question: What did the
      experience of massaging your child mean to you? RESULTS: The experience of
      massaging their children meant the development of their being a mother and of
      being a son/daughter, in addition to developing the attachment relationship
      between them. The massage can operationalize this integrality, become a tool of
      communication, stimulation and promotion of secure attachment, by promoting the
      loving interaction between mother and child. CONCLUSION: This practice should be
      considered as an option in the programs that promote the comprehensive health of
      the mother and child.

PMID- 25076269
TI  - [Therapeutic play in preparing for surgery: behavior of preschool children during
      the perioperative period].
AB  - OBJECTIVE: to describe the behavior of children during the instructional session
      of therapeutic play (ITP) in the preoperative period and to verify the behavior
      presented by them during the perioperative period. METHODS: Exploratory
      descriptive study with a quantitative approach, developed in a large private
      hospital in Sao Paulo, in which the behaviors presented by 30 children between
      three and five years old, undergoing minor surgery were seen at the hospital
      during the session of TP and in the surgical center, from admission to awaken
      from anesthesia. RESULTS: Most children participated in the ITP session (21;
      70%), entered the surgical room spontaneously (22; 73.3%) without resisting
      mother separation (24; 80%), collaborating with the anesthetic procedure (16;
      53.3%) and quietly awakening from anesthesia (26; 87%). CONCLUSION: The use of
      ITP led the child to understand the surgical procedure, making it less traumatic.

PMID- 25076270
TI  - [The use of the Family Management Style Framework to evaluate the family
      management of liver transplantation in adolescence].
AB  - OBJECTIVE: To understand the family management experience of liver
      transplantation during adolescence based on the Family Management Style
      Framework(FMSF). METHOD: This is a case study that used the FMSF as theoretical
      framework and the hybrid model of thematic analysis as methodological reference.
      The case presented is from an adolescent's family that lives in Salvador, Bahia.
      The data were collected through interviews with the mother and the patient charts
      analysis. RESULTS: The results shows that the family defines the transplantation
      as threatening and there are divergence between mother and daughter related to
      the teen's capabilities perception. Facing those discrepancies, the family
      assumes a protective posture by believing that the teen cannot take care of
      herself alone. The perceived consequences reflect how much the uncertainty
      permeates the family environment. CONCLUSION: It is concluded that the use of a
      model to evaluate the management can help professionals to direct and plan
      specific interventions.

PMID- 25076271
TI  - [The representations of adolescents about gynecological consultation].
AB  - OBJECTIVE: To analyze the social representation of adolescents about
      gynecological consultation and the influence of those in searching for
      consultations. METHOD: Qualitative descriptive study based on the Social
      Representations Theory, conducted with 50 adolescents in their last year of
      middle school. The data was collected between April and May of 2010 by Evocations
      and a Focal Group. The software EVOC and contextual analysis were used in the
      data treatment. RESULTS: The elements fear and constraint, constant in the
      central nucleus, can justify the low frequency of adolescents in consultations.
      The term embarrassment in the peripheral system reinforce current sociocultural
      norms, while prevention, associated with learning about sex and clarifying
      doubts, allows to envision an educative function. Obtained testimonies in the
      focal groups exemplify and reinforce those findings. CONCLUSION: For an effective
      health education, professionals, including nurses, need to clarify the youth
      individually and collectively about their rights to privacy, secrecy, in addition
      to focus the gynecological consultation as a promotion measure to sexual and
      reproductive health.

PMID- 25076272
TI  - [Prevalence of nursing diagnosis of fluid volume excess in patients undergoing
      hemodialysis].
AB  - OBJECTIVE: To identify the prevalence of nursing diagnosis of fluid volume excess
      and their defining characteristics in hemodialysis patients and the association
      between them. METHOD: Cross-sectional study conducted in two steps. We
      interviewed 100 patients between the months of December 2012 and April 2013 in a
      teaching hospital and one hemodialysis clinic. The inference was performed by
      diagnostician nurses between July and September 2013. RESULTS: The diagnostic
      studied was identified in 82% of patients. The characteristics that were
      statistically associated: bounding pulses, pulmonary congestion, jugular vein
      distention, edema, change in electrolytes, weight gain, intake greater than
      output and abnormal breath sounds. Among these, edema and weight gain had the
      highest chances for the development of this diagnostic. CONCLUSION: The analyzed
      diagnostic is prevalent in this population and eight characteristics presented
      significant association.

PMID- 25076273
TI  - [Mapping the nursing care with the NIC for patients in risk for pressure ulcer].
AB  - OBJECTIVE: To identify the nursing care prescribed for patients in risk for
      pressure ulcer (PU) and to compare those with the Nursing Interventions
      Classification (NIC) interventions. METHOD: Cross mapping study conducted in a
      university hospital. The sample was composed of 219 adult patients hospitalized
      in clinical and surgical units. The inclusion criteria were: score <= 13 in the
      Braden Scale and one of the nursing diagnoses, Self-Care deficit syndrome,
      Impaired physical mobility, Impaired tissue integrity, Impaired skin integrity,
      Risk for impaired skin integrity. The data were collected retrospectively in a
      nursing prescription system and statistically analyzed by crossed mapping.
      RESULT: It was identified 32 different nursing cares to prevent PU, mapped in 17
      different NIC interventions, within them: Skin surveillance, Pressure ulcer
      prevention and Positioning. CONCLUSION: The cross mapping showed similarities
      between the prescribed nursing care and the NIC interventions.

PMID- 25076274
TI  - [Cultural adaptation of the scale Pain Assessment in Advanced Dementia - PAINAD
      to Brazil].
AB  - OBJECTIVE: To translate and culturally adapt to Brazil the scale Pain Assessment
      in Advanced Dementia(PAINAD). METHOD: The cultural adaptation process followed
      the methodology of a theorical reference, in five steps: translation to Brazilian
      Portuguese, consensual version of translations, back-translation to the original
      language, revision by a committee of specialists in the field and a equivalency
      pre-test. The instrument was assessed and applied by 27 health professionals in
      the last step. RESULTS: The Escala de Avaliacao de Dor em Demencia Avancada was
      culturally adapted to Brazil and presented semantic equivalency to the original,
      besides clarity, applicability and easy comprehension of the instrument items.
      CONCLUSION: This process secured the psychometric properties as the reliability
      and content validity of the referred scale.

PMID- 25076275
TI  - [Family functioning of elderly with depressive symptoms].
AB  - OBJECTIVE: To classify families of elderly with depressive symptoms regarding
      their functioning and to ascertain the presence of an association between these
      symptoms, family functioning and the characteristics of the elderly. METHOD: This
      was an observational, analytical, cross-sectional study performed with 33 teams
      of the Family Health Strategy in Dourados, MS. The sample consisted of 374
      elderly divided into two groups (with and without depressive symptoms). The
      instruments for data collection were a sociodemographic instrument, the
      GeriatricDepression Scale (15 items) and the Family Apgar. RESULTS: An
      association was observed between depressive symptoms and family dysfunction,
      female gender, four or more people living together, and physical inactivity.
      CONCLUSION: The functional family may represent effective support for the elderly
      with depressive symptoms, because it offers a comfortable environment that
      ensures the well-being of its members. The dysfunctional family can barely
      provide necessary care for the elderly, which can exacerbate depressive symptoms.

PMID- 25076276
TI  - [Adherence to statin treatment and associated factors in female users from the
      Unified Health System (SUS)].
AB  - OBJECTIVE: To identify the adherence rate of a statin treatment and possible
      related factors in female users from the Unified Health System. METHOD: Seventy
      one women were evaluated (64.2 +/- 11.0 years) regarding the socio-economic
      level, comorbidities, current medications, level of physical activity, self
      report of muscular pain, adherence to the medical prescription, body composition
      and biochemical profile. The data were analyzed as frequencies, Chi-Squared test,
      and Mann Whitney test (p<0.05). RESULTS: 15.5% of women did not adhere to the
      medical prescription for the statin treatment, whose had less comorbidities
      (p=0.01), consumed less quantities of medications (p=0.00), and tended to be
      younger (p=0.06). Those patients also presented higher values of lipid profile
      (CT: p=0.01; LDL-c: p=0.02). Musculoskeletal complains were not associated to the
      adherence rate to the medication. CONCLUSION: The associated factors to adherence
      of dyslipidemic women to statin medical prescription were age, quantity of
      comorbidities and quantity of current medication.

PMID- 25076277
TI  - [The network social support experience of people involved in home care].
AB  - OBJECTIVE: To build a theoretical model to configure the network social support
      experience of people involved in home care. METHOD: A quantitative approach
      research, utilizing the Grounded Theory method. The simultaneous data collection
      and analysis allowed the interpretation of the phenomenon meaning The network
      social support of people involved in home care. RESULTS: The population passive
      posture in building their well-being was highlighted. The need of a shared
      responsibility between the involved parts, population and State is recognized.
      CONCLUSION: It is suggested for nurses to be stimulated to amplify home care to
      attend the demands of caregivers; and to elaborate new studies with different
      populations, to validate or complement the proposed theoretical model.

PMID- 25076278
TI  - [Aromatherapy with ylang ylang for anxiety and self-esteem: a pilot study].
AB  - OBJECTIVE: To verify if the use of ylang ylang essential oil by cutaneous
      application or inhalation alters the anxiety and self-esteem perception and
      physiological parameters as blood pressure and temperature. Method : A pilot
      study with 34 professionals from a nursing group randomized in three groups: one
      received the ylang ylang essential oil by cutaneous application, the second
      received through inhalation and the third (placebo) received the ylang ylang
      essence through cutaneous application. The assessment was done by an Anxiety
      Inventory (IDATE) and the Dela Coleta self-esteem scale, applied on baseline,
      after 30, 60 and 90 days and after 15 days post-intervention (follow up). Results
      : In the pre and post-intervention intergroup analysis, there was a significant
      difference in self-esteem for the three groups (p values: G1=0.014; G2=0.016;
      G3=0.038). There were no differences in the analysis between groups for anxiety
      or for physiological parameters. Conclusion : It was found significant
      alterations only to the intergroup perception of self-esteem for the three
      groups.

PMID- 25076279
TI  - [The opinion of patients with mental disorder about tobacco and its prohibition
      in psychiatric hospitalization].
AB  - OBJECTIVE: To identify the opinion of patients with mental disorder about tobacco
      and its prohibition during psychiatric hospitalization. METHOD: An exploratory
      study with 96 patients smokers with mental disorders hospitalized in a
      psychiatric ward of a general hospital. The interviews were conducted
      individually, using an instrument designed for this study. The content from the
      interviews was recorded, transcribed and submitted to a thematic content
      analysis. RESULTS: The patients with mental disorder were identified as
      perceiving smoking during the psychiatric hospitalization as a help to support
      the difficulties in socialization and in the lack of activities. The permission
      for smoking is seen as a signal of respect to their needs. The subjects mentioned
      to not accept the total smoking prohibition. CONCLUSION: Tobacco helps to face
      difficulties and conflicts in the psychiatric hospitalization. There is
      resistance regarding the possibility to totally withdraw the smoking permission
      during hospitalization.

PMID- 25076280
TI  - [Intervening factors in attention flow of professionals injured by biological
      material].
AB  - OBJECTIVE: To describe the barriers and facilitator factors to follow the
      attention flow of professionals injured by biological material in the worker
      perspective. METHOD: Qualitative descriptive study with data collected through
      individual interviews with 18 injured workers, assisted in reference public units
      in the city of Goiania. The content analysis was carried out with assistance of
      the ATLAS.ti 6.2 software, under the work organization and subjective
      perspectives. RESULTS: From the interviews regarding the barriers and facilitator
      factors emerged the categories: organizational structure, Support from close
      people, and Knowledge influence. CONCLUSION: The organized services have enabled
      more qualified consultations and the workers follow-up, which caused a
      satisfaction feeling in relation to the working environment.

PMID- 25076281
TI  - [Influence of stress factors and socio-demographic characteristics on the sleep
      quality of nursing students].
AB  - OBJECTIVE: To analyze the influence of stress factors and socio-demographic
      characteristics on the sleep quality of nursing students. METHOD: An analytical
      cross-sectional and quantitative study, conducted with 151 nursing students in
      Sao Paulo between March and April of 2012. A form for socio-demographic
      characteristics, the Instrument to Evaluate Stress in Nursing Students and the
      Pittsburgh Sleep Index were applied. RESULTS: High levels of stress was
      predominant for Time Management (27.8%) and Professional Training (30.5%) and low
      sleep quality (78.8%). The Professional Communication, Professional Training and
      Theoretical Activity are positively correlated to sleep quality. Work activity,
      academic year and time for daily studies contributed to a low quality of sleep.
      CONCLUSION: Few stress factors from the academic environment and some socio
      demographic characteristics contributed to the reduction of sleep quality in
      students.

PMID- 25076282
TI  - [Nurses, nursing technicians and assistants: who experiences more moral
      distress?].
AB  - OBJECTIVE: To identify the frequency and intensity of moral distress experienced
      by nurses, technicians and nursing assistants who worked in hospitals in the
      South of Rio Grande do Sul State. METHOD: A survey research was conducted with
      334 nursing workers from three institutions, through a questionnaire of moral
      distress. Constructs were validated through factorial analysis and Cronbach's
      alpha: lack of competence of the working team, disrespect to the patient's
      autonomy, insufficient working conditions and therapeutic obstinacy. RESULTS:
      With descriptive statistics and analysis of variance, it was found that nurses
      and nursing assistants have higher perception of moral distress when compared to
      nursing technicians. Organizational questions and ways of communication influence
      lower perception of moral distress. CONCLUSION: Implementation of actions to
      favor coping, decision making and autonomy exercise from those workers.

PMID- 25076283
TI  - [Health facility environment as humanization strategy care in the pediatric unit:
      systematic review].
AB  - OBJECTIVE: To identify and analyze the production of knowledge about the
      strategies that health care institutions have implemented to humanize care of
      hospitalized children. METHOD: This is a systematic review conducted in the
      Virtual Health Library - Nursing and SciELO, using the seven steps proposed by
      the Cochrane Handbook. RESULTS: 15 studies were selected, and strategies that
      involved relationship exchanges were used between the health professional, the
      hospitalized child and their families, which may be mediated by leisure
      activities, music and by reading fairy tales. We also include the use of the
      architecture itself as a way of providing welfare to the child and his/her
      family, as well as facilitating the development of the work process of health
      professionals. CONCLUSION: Investments in research and publications about the
      topic are necessary, so that, the National Humanization Policy does not disappear
      and that the identified strategies in this study do not configure as isolated and
      disjointed actions of health policy.

PMID- 25076284
TI  - [Risk factors for falls in hospitalized adult patients: an integrative review].
AB  - OBJECTIVE: Identifying risk factors for the occurrence of falls in hospitalized
      adult patients. METHOD: Integrative review carried out in the databases of
      LILACS, SciELO, MEDLINE and Web of Science, including articles published between
      1989 and 2012. RESULTS: Seventy-one articles were included in the final sample.
      Risk factors for falls presented in this review were related to patients
      (intrinsic), the hospital setting and the working process of health
      professionals, especially in nursing (extrinsic). CONCLUSION: The systematic
      screening of risk factors for falls was identified as a contributing factor to
      the reduction of this injury, helping the non-occurrence of this event that,
      despite being preventable, can have serious consequences including death.

PMID- 25076285
TI  - [Risk factors associated with mental health issues in adolescents: a integrative
      review].
AB  - OBJECTIVE: To identify the risk factors associated with mental health issues in
      adolescents. METHOD: An integrative review was conducted in four databases with
      publications from 2007 to 2013. The terms Adolescent and Mental Health were used
      to search adequate articles as DeCs/MeSH bases. RESULTS: Publications were found
      in different journals in different fields of knowledge and the quantitative
      research was the most frequent. The mental health issues were categorized as
      individual factors; drug related factors, school factors, family factors, social
      factors and STDs/Aids related factors. The most addressed category was individual
      factors, with 23 publications. CONCLUSION: The integrative review allowed to
      point important questions to be addressed in preventive actions by the health
      professional, including the nurse, to create a space that works with risk
      conditioning factors in adolescents for mental health aggravation.

PMID- 25076287
TI  - Corporate culture in decision making.

PMID- 25076288
TI  - Pathologist workforce in the United States.

PMID- 25076289
TI  - Social media: pathologists' force multiplier.

PMID- 25076290
TI  - Clinical consequences of specimen rejection: a College of American Pathologists Q
      Probes analysis of 78 clinical laboratories.
AB  - CONTEXT: Clinical laboratory specimens may be rejected as unsuitable for analysis
      for a variety of reasons and specimen rejection may have significant clinical
      consequences. OBJECTIVE: To quantify the clinical consequences of specimen
      rejection and determine the impact of laboratories' policies and practices on
      these consequences. DESIGN: Participants prospectively reviewed consecutive blood
      and urine specimens submitted to the chemistry and/or hematology laboratories to
      identify rejected specimens. For each rejected specimen, the patient's age,
      specimen type, testing priority, rejection reason, time from specimen receipt to
      receipt of recollected/relabeled specimen, recollection method, and test result
      time were recorded. Specimen/test abandonment was determined by failure to
      recollect or relabel a rejected specimen. Each laboratory's policy regarding
      relabeling of incorrectly labeled specimens was recorded, along with how many
      relabeled specimens were subsequently discovered to be mislabeled. RESULTS:
      Specimen rejection led to a (1) high rate of specimen recollection, (2) delay in
      result availability (median of 65 minutes), and (3) high rate of specimen/test
      abandonment. Longer test result delay was associated with higher hospital bed
      size; and higher test abandonment rate, with failure of the laboratory to request
      specimen recollection. Relabeling of incorrectly labeled specimens was found to
      be of little benefit and was associated with a substantial percentage of
      subsequently mislabeled specimens. CONCLUSION: Specimen rejection has significant
      clinical consequences, including patient discomfort, significant delay in result
      availability, and high rate of specimen/test abandonment. Allowing routine
      relabeling of incorrectly labeled specimens is a dangerous practice, with little
      measureable benefit and with an increased risk to patient safety.

PMID- 25076291
TI  - Frequency monitoring of hemoglobin A1c, low-density lipoprotein, and urine
      protein laboratory testing: a College of American Pathologists Q-Probes study.
AB  - CONTEXT: Ensuring laboratory tests are performed at intervals consistent with
      established, evidence-based guidelines in diabetic patients is an important
      aspect of laboratory utilization. OBJECTIVES: To measure how frequently diabetes
      mellitus patients are tested for hemoglobin A1c (HbA1c), low-density lipoprotein,
      and urine protein and to determine whether the frequencies with which these
      analytes are tested are consistent with recognized guidelines. DESIGN:
      Participants prospectively identified up to 40 patients with a current HbA1c
      result and at least 2 previous measurements within the past 24 months. For each
      patient identified with at least 3 HbA1c measurements during a 24-month period,
      participants also determined the number of low-density lipoprotein and spot or
      random urine protein tests that were performed during those 24 months. RESULTS:
      Participants from 49 institutions submitted a total of 1915 cases that met the
      study criteria of at least 3 HbA1c test results within the past 24 months.
      Approximately 95% of patients had 8 or fewer HbA1c tests in the past 24 months;
      79% of patients with at least 3 HbA1c tests had at least 2 low-density
      lipoprotein tests and 27% had at least 2 urine protein tests reported during the
      24-month study period. CONCLUSION: Participating laboratories were generally
      successful in documenting appropriate utilization of HbA1c testing in diabetes
      mellitus monitoring, but had more difficulty documenting that diabetes mellitus
      patients had annual testing for low-density lipoprotein and urine protein.

PMID- 25076292
TI  - Progesterone receptor and PTEN expression predict survival in patients with low-
      and intermediate-grade pancreatic neuroendocrine tumors.
AB  - CONTEXT: The PI3K-AKT-mTOR (phosphatidylinositol 3-kinase-AKT-mammalian target of
      rapamycin) pathway plays a crucial role in a subset of advanced pancreatic
      neuroendocrine tumors (PanNETs). In breast and endometrial carcinoma, activation
      of this pathway inhibits progesterone receptor (PR) expression. OBJECTIVE: To
      determine whether combined low expression of PR and phosphatase and tensin
      homologue (PTEN), a negative regulator of the PI3K-AKT-mTOR pathway, is a
      prognostic factor. DESIGN: A total of 160 resected PanNETs (89 low grade and 71
      intermediate grade) were analyzed for PR and PTEN immunohistochemical positivity
      and staining was correlated with metastasis-free survival (MFS) and overall
      survival (OS). Progesterone receptor staining was scored as positive by using 1%
      or greater as cutoff. Weak/faint staining in greater than 90% of tumor cells was
      considered low PTEN positivity. RESULTS: Most PanNETs (110 cases, 69%) were both
      PR and PTEN positive, 45 (28%) were either PR or PTEN positive, and only 5 (3%)
      had a PR-negative and PTEN-low profile. Combined PR-PTEN positivity was
      significantly associated with MFS in patients with stage I and II disease (P
      <.001) and OS in all patients (P < .001) and remained a significant predictor of
      survival after adjusting for other factors. Patients with PR-negative-PTEN-low
      PanNETs had the shortest median MFS and OS, compared to those with tumors that
      were either PR or PTEN positive and with tumors positive for both PR and PTEN (P
      <= .001). CONCLUSION: Combined immunohistochemical assessment of PR and PTEN may
      help identify a small subset of PanNETs with more aggressive behavior and may aid
      in risk stratification.

PMID- 25076293
TI  - Histologic grade remains a prognostic factor for breast cancer regardless of the
      number of positive lymph nodes and tumor size: a study of 161 708 cases of breast
      cancer from the SEER Program.
AB  - CONTEXT: The appropriate staging of breast cancers includes an evaluation of
      tumor size and nodal status. Histologic grade in breast cancer, though important
      and assessed for all tumors, is not integrated within tumor staging. OBJECTIVE:
      To determine whether the histologic grade remains a prognostic factor for breast
      cancer regardless of tumor size and the number of involved axillary lymph nodes.
      DESIGN: By using a new clustering algorithm, the 10-year survival for every
      combination of T, N, and the histologic grade was determined for cases of breast
      cancer obtained from the Surveillance, Epidemiology, and End Results Program of
      the National Cancer Institute. There were 36 combinations of TN, defined
      according to the American Joint Committee on Cancer, and grade. RESULTS: For each
      combination of T and N, a categorical increase in the histologic grade was
      associated with a progressive decrease in 10-year survival regardless of the
      number of involved axillary lymph nodes or size of the primary tumor. Absolute
      survival differences between high and low grade persisted despite larger tumor
      sizes and greater nodal involvement, though trends were apparent with increasing
      breast cancer stage. Statistical significance depended on the number of cases for
      each combination. CONCLUSIONS: Histologic grade continues to be of prognostic
      importance for overall survival despite tumor size and nodal status. Furthermore,
      these results seem to indicate that the assignment of the histologic grade has
      been consistent among pathologists when evaluated in a large data set of patients
      with breast cancer. The incorporation of histologic grade in TNM staging for
      breast cancer provides important prognostic information.

PMID- 25076294
TI  - Is pneumatosis cystoides intestinalis gas-distended and ruptured lymphatics?
      Reappraisal by immunohistochemistry.
AB  - CONTEXT: Pneumatosis cystoides intestinalis (PCI) is a condition with multiple
      gas-filled cysts within the bowel wall, associated with diverse background
      diseases. Its pathogenesis is still a mystery. Some previous observations
      scattered in the literature have suggested an association of the cystic spaces in
      PCI with the lymphatics. OBJECTIVE: To further investigate whether PCI results
      from the ballooning of gas-filled lymphatic channels. DESIGN: We did
      immunostaining of podoplanin, a mucoprotein preferentially expressed in lymphatic
      endothelial cells, in 13 cases (8 men, 5 women; age range, 18-80 years) of PCI.
      Ten cases were diagnosed in resected segments of bowel and 3 in biopsies.
      Pneumatosis was seen in the right side of the colon (9 cases), transverse colon
      (1 case), sigmoid colon (1 case), and small bowel (2 cases). In addition,
      immunostaining for CD31, calretinin, WT1, CD68, smooth muscle actin, desmin,
      vimentin, and cytokeratins was also performed for comparison and correlation.
      RESULTS: A strong immunopositivity of podoplanin was seen in a condensed linear
      structure in the pericystic interstitium in 100% of the cases, but was not seen
      in the overlying giant and flat cells that were all CD68-positive histiocytes.
      Meanwhile, the podoplanin-expressing structure was negative for calretinin and
      WT1, which ruled out the possible mesothelial origin. There were coexistent
      variable immunopositivity of smooth muscle actin, which suggests an admixture of
      myofibroblasts. These findings indicated that the PCI cases were gas-distended
      lymphatics with the lymphatic epithelium ruptured and embedded in the reactive
      histiocytes and giant cells. CONCLUSION: Our findings support the lymphatic
      theory about the pathogenesis of PCI.

PMID- 25076295
TI  - Polyclonal napsin A expression: a potential diagnostic pitfall in distinguishing
      primary from metastatic mucinous tumors in the lung.
AB  - CONTEXT: Napsin A is a useful marker for distinguishing primary from metastatic
      lung tumors. Mucinous lung tumors may be difficult to distinguish from metastatic
      mucinous tumors. OBJECTIVES: To evaluate napsin A expression in lung and
      extrapulmonary mucinous tumors on both histology and cytology specimens and to
      determine napsin A's utility in differentiating primary from metastatic mucinous
      tumors. DESIGN: Napsin A immunohistochemistry was performed using a rabbit
      polyclonal antibody on formalin-fixed, paraffin-embedded surgical and fine-needle
      aspiration biopsy-derived, paraffin-embedded cell block specimens. Positive
      expression was defined as coarse, granular, cytoplasmic staining in 10% or more
      of tumor cells. RESULTS: Sixteen of 32 mucinous lung tumors (50%) and 16 of 33
      extrapulmonary mucinous tumors (48%), including 15 of 18 of gastrointestinal
      origin (83%), expressed napsin A. Positivity was concordant between surgical and
      cell block specimens in 5 of 9 cases (56%). In 3 of 4 discordant cases, napsin A
      expression was detected on the surgical specimen but not the cell block. The cell
      block material in these cases was paucicellular. CONCLUSIONS: Napsin A shows
      decreased sensitivity and specificity for mucinous lung tumors and is unlikely to
      be reliable as a sole immunohistochemical marker of lung origin for such tumors
      (52% specificity in this study). The high frequency of napsin A expression in
      gastrointestinal mucinous tumors makes it particularly unreliable in
      distinguishing metastatic gastrointestinal from primary lung mucinous tumors.
      However, napsin A expression analysis may facilitate distinguishing mucinous
      tumors of pulmonary from those of nongastrointestinal origin. Interpretation of
      napsin A staining may be problematic in mucinous tumor specimens of low
      cellularity such as cell blocks.

PMID- 25076296
TI  - Pathologic T1 subclassification of ampullary carcinoma with perisphincteric or
      duodenal submucosal invasion: Is it T1b?
AB  - CONTEXT: In ampullary carcinoma staging, T1 is defined as a tumor limited to the
      ampulla of Vater or the sphincter of Oddi, and T2 is defined as invasion into the
      duodenal wall. However, the definition of duodenal wall invasion is vague.
      Ampullary carcinoma that invades beyond the sphincteric of Oddi (perisphincteric
      invasion) or into the duodenal submucosa could be considered pT1b because
      submucosal invasion is classified as pT1b in gastrointestinal tract tumors.
      However, there are no data regarding T subclassifications for ampullary carcinoma
      with perisphincteric or duodenal submucosa invasion. OBJECTIVE: To determine the
      T subclassification of ampullary carcinoma that invades into perisphincteric or
      duodenal submucosa. DESIGN: Pathologically proven ampullary carcinomas with T1 or
      T2 were reviewed (n = 105). We reclassified tumors as pT1a that were limited to
      within the sphincter of Oddi (n = 40; 38%), as pT1b for tumors that invaded
      beyond the sphincter of Oddi or into the duodenal submucosa (n = 25; 24%), and as
      pT2 for tumors that invaded into duodenal proper muscle (n = 40; 38%). RESULTS:
      Lymph node metastasis and recurrence were absent in ampullary carcinoma with
      pT1a, whereas nodal metastasis were noted in 24% (6 of 25) and 40% (16 of 40) of
      the ampullary carcinomas with pT1b and pT2, respectively. Tumor
      recurrence/metastasis rate of ampullary carcinoma with pT1b and pT2 was 44% (11
      of 25) and 40% (16 of 40), respectively. The 5-year disease-free-survival rates
      from ampullary carcinoma with pT1a, pT1b, and pT2 were 95% (38 of 40), 56% (14 of
      25), and 58% (23 of 40), respectively (P = .003). The 5-year overall survival
      from ampullary carcinoma with pT1a, pT1b, and pT2 was 98% (39 of 40), 72% (18 of
      25), and 60% (24 of 40), respectively. CONCLUSIONS: The clinicopathologic outcome
      of ampullary carcinoma with a pT1b subclassification was worse than it was for
      T1a and approached the outcome for pT2.

PMID- 25076297
TI  - Performance evaluation of Samsung LABGEO(HC10) Hematology Analyzer.
AB  - CONTEXT: The Samsung LABGEO(HC10) Hematology Analyzer (LABGEO(HC10)) is a
      recently developed automated hematology analyzer that uses impedance
      technologies. The analyzer provides 18 parameters including 3-part differential
      at a maximum rate of 80 samples per hour. OBJECTIVE: To evaluate the performance
      of the LABGEO(HC10). DESIGN: We evaluated precision, linearity, carryover, and
      relationship for complete blood cell count parameters between the LABGEO(HC10)
      and the LH780 (Beckman Coulter Inc) in a university hospital in Korea according
      to the Clinical and Laboratory Standards Institute guidelines. Sample stability
      and differences due to the anticoagulant used (K2EDTA versus K3EDTA) were also
      evaluated. RESULTS: The LABGEO(HC10) showed linearity over a wide range and
      minimal carryover (<1%) for white blood cell, hemoglobin, red blood cell, and
      platelet parameters. Correlation between the LABGEO(HC10) and the LH780 was good
      for all complete blood cell count parameters (R > 0.92) except for mean
      corpuscular hemoglobin concentration. The bias estimated was acceptable for all
      parameters investigated except for monocyte count. Most parameters were stable
      until 24 hours both at room temperature and at 4 degrees C. The difference by
      anticoagulant type was statistically insignificant for all parameters except for
      a few red cell parameters. CONCLUSIONS: The accurate results achievable and
      simplicity of operation make the unit recommendable for small to medium-sized
      laboratories.

PMID- 25076298
TI  - Update on the new classification of hepatic adenomas: clinical, molecular, and
      pathologic characteristics.
AB  - CONTEXT: Hepatic adenoma is an uncommon, benign, hepatic neoplasm that typically
      occurs in women of child-bearing age, often with a history of long-term use of
      oral contraceptive drugs. This is usually detected as an incidental mass lesion
      in a noncirrhotic liver during imaging studies. Pathologic evaluation by needle
      core biopsy remains the gold standard for diagnosis. Molecular studies have
      revealed that hepatic adenomas involve unique molecular pathways that are
      distinct from hepatocellular carcinoma. Based on these studies, a French
      collaborative group has recently proposed a molecular-pathologic classification
      for hepatic adenomas. In addition, advances in molecular studies have led to
      reclassification of the "telangiectatic variant of focal nodular hyperplasia" as
      "hepatic adenoma, inflammatory subtype." OBJECTIVE: To review the proposed, new
      classification of hepatic adenoma and the changes in diagnostic workup in light
      of the above-mentioned developments. DATA SOURCES: Review of published literature
      and illustrations from clinical case material. CONCLUSIONS: Definitive diagnosis
      of liver mass lesion on needle core biopsies has a decisive role in clinical
      management. With the advent of the new classification of hepatic adenomas and its
      prognostic implications, it is vital for pathologists to be aware of the
      morphologic features seen in different subtypes and the available diagnostic
      tools, such as immunohistochemistry, to help identify the correct subtype.

PMID- 25076299
TI  - Ossifying fibromyxoid tumor of the breast mimicking fibroadenoma: a case report
      and differential diagnoses.
AB  - An 80-year-old woman presented with a palpable mass in the right breast.
      Mammographic findings were consistent with calcified fibroadenoma. An ultrasound
      was performed that showed a solid nodule with peripheral calcification. A core
      biopsy was obtained that revealed a spindle cell proliferation with a shell of
      mature bone. The histologic features, in combination with immunohistochemical
      studies, were those of an ossifying fibromyxoid tumor. Complete excision of the
      specimen further confirmed the diagnosis. To the best of our knowledge, this is
      the first reported case of ossifying fibromyxoid tumor occurring in the breast.
      We review the current literature on ossifying fibromyxoid tumor and discuss the
      differential diagnoses when confronted with bland spindle cells on a core biopsy
      of the breast. 

PMID- 25076300
TI  - Transformation of small B-cell lymphoma into large cell CD30+, CD4+, Epstein-Barr
      virus-negative lymphoma.
AB  - We report here 2 separate cases in which patients with known low-grade B-cell
      lymphomas presented with transformed lesions that were CD30+, CD4+, Epstein-Barr
      virus negative, and negative or focally weak for a wide range of B-cell, T-cell,
      and histiocytic/dendritic cell markers. In each case the transformed lymphoma
      possessed an identical pattern of immunoglobulin heavy chain and/or BCL2
      rearrangement to the corresponding original low-grade B-cell lymphoma, confirming
      their identity as transformed B-cell lymphoma. A review of the relevant
      literature reveals that, to our knowledge, no transformed B-cell lymphomas with
      this immunophenotype have been previously reported, which creates the opportunity
      for potential errors of diagnosis. These cases highlight the importance of
      correlation with the patient's history and with molecular genetic results in
      rendering an accurate diagnosis.

PMID- 25076301
TI  - Localized cutaneous infections in immunocompetent individuals due to rapidly
      growing mycobacteria.
AB  - Rapidly growing mycobacteria (RGM) cause skin infections that are refractory to
      standard antibiotic regimens. Although typically associated with disseminated
      cutaneous or other systemic infections in immunocompromised patients, RGM
      sometimes cause localized cutaneous infections in immunocompetent hosts. These
      infections are almost always associated with precedent skin trauma and
      inoculation, and therefore have been implicated in outbreaks involving
      contaminated tattoo ink and inadequately sterilized acupuncture needles.
      Histologic features often include suppurative granulomatous inflammation, and
      microorganisms are rarely visualized with stains for acid-fast bacilli. The
      differential diagnosis includes granulomatous fungal and non-RGM bacterial
      infections as well as noninfectious suppurative or sarcoidlike conditions.
      Because no pathognomonic histologic features exist for cutaneous RGM infections,
      clinical suspicion and appropriate workup are essential to reach an accurate and
      timely diagnosis. Most localized cutaneous RGM infections in immunocompetent
      individuals respond well to either clarithromycin or amikacin, in combination
      with surgical debridement. 

PMID- 25076303
TI  - Uterine angioleiomyoma: a rare variant of uterine leiomyoma.
AB  - Uterine angioleiomyoma is an extremely rare and unique variant of leiomyoma. It
      usually occurs in middle-aged women, who commonly present with menorrhagia,
      abdominal pain, or abdominal mass. The lesions are either single or multiple and
      manifest as submucosal, intramural, or subserosal whorled nodules. Microscopy of
      the individual nodule shows interlacing fascicles of spindle cells swirling
      around thick-walled blood vessels. Angioleiomyoma usually lacks mitotic figures,
      pleomorphism, or necrosis, although cases with marked nuclear atypia and
      multinucleated giant cells have been reported. The tumor cells are immunoreactive
      for smooth muscle actin, desmin, h-caldesmon, and progesterone receptor, with a
      low Ki-67 labeling index. Because these lesions are vascular, they may undergo
      spontaneous rupture and pose a life-threatening emergency, especially in
      pregnancy. There are no specific imaging findings; therefore, a preoperative
      diagnosis is extremely difficult. It is important to recognize this entity and
      differentiate it from a malignancy, particularly when angioleiomyoma shows
      significant cytologic atypia or raised cancer antigen 125 levels by thorough
      sampling. When required, a proper immunohistochemical panel should be used to
      arrive at a correct diagnosis. In this review, we discuss the current knowledge
      on uterine angioleiomyoma and its clinical relevance. 

PMID- 25076302
TI  - Orbital granulomatosis with polyangiitis (Wegener granulomatosis): clinical and
      pathologic findings.
AB  - The pathology of granulomatosis with polyangiitis (GPA), formerly Wegener
      granulomatosis, typically features a granulomatous and sometimes necrotizing
      vasculitis targeting the respiratory tract and kidneys. However, orbital
      involvement occurs in up to 60% of patients and is frequently the first or only
      clinical presentation in patients with systemic or limited forms of GPA. Orbital
      GPA can cause significant morbidity and potentially lead to complete loss of
      vision and permanent facial deformity. Fortunately, GPA is highly responsive to
      medical treatment with corticosteroids combined with cyclophosphamide or, more
      recently, rituximab. Therefore, it is imperative for this disease to be
      accurately diagnosed on orbital biopsy and distinguished from other
      histologically similar orbital lesions. Herein, we review the clinical and
      pathologic findings of orbital GPA, focusing on the differentiation of this
      disease from other inflammatory orbital lesions. 

PMID- 25076304
TI  - [The basis for our actions].

PMID- 25076305
TI  - [Hemodialysis vascular access].

PMID- 25076306
TI  - [Endocrine changes in critically ill patients].

PMID- 25076307
TI  - [Options for renal replacement therapy in geriatric patients].

PMID- 25076308
TI  - [Systemic mastocytosis].

PMID- 25076309
TI  - [A zoonotic viral threat: news about hantavirus disease].

PMID- 25076310
TI  - [Prolonged weaning--the German S2k guideline].

PMID- 25076311
TI  - [Aortic valvular disease].

PMID- 25076312
TI  - [Sodium- and fluid balance].

PMID- 25076313
TI  - [Testing lung function: what is new?].

PMID- 25076314
TI  - [Infections during antirheumatic treatment].

PMID- 25076315
TI  - [Food intolerances].

PMID- 25076316
TI  - [55-year old woman with unclear skin finding].

PMID- 25076317
TI  - [To prevent HPV-associated neoplasia].

PMID- 25076318
TI  - [Ventricular fibrillation or general seizure?].
AB  - HISTORY AND CLINICAL FINDINGS: A 78-year-old patient seemed to have recurrent
      seizures due to marginal hypoglycaemia. He was initially awake with stable
      circulation. Subsequently, he lost consciousness followed by extensie twitching
      arms of his arms and the upper part of his body. Thereafter, the patient was
      somnolent, but accessible. INVESTIGATIONS AND TREATMENT: Initially hypoglycemia
      was thought to have caused general seizures. But the ECG monitor showed
      repetitive ventricular fibrillation, which was terminated by a cardioverter
      defibrillator that had been implanted 3 years previously because of dilatative
      cardiomyopathy. At admission to hospital, marked hypokalemia (1,8 mmol/l) was
      noted as the cause of ventricular fibrillation. After normalization of serum
      potassium no further events occurred. CONCLUSION: Disorders of consciousness
      always request an ECG for early diagnosis.

PMID- 25076319
TI  - [Patient care at the interface between rehabilitation and occupational health
      physicians--a systematic literature review focusing health care organization].
AB  - Principal goal of rehabilitation arrangements for patients in employable age are
      the preservation of the ability to work, the rehabilitation of employability and
      the prompt reintegration into the professional life respectively. In practice,
      the reintegration is achieving unsatisfactory results.The systematic literature
      research (acquisition period: 1998-2013) was conducted on the basis of defined
      search keywords in electronic databases, online archives, relevant German
      magazines (via manual search), and in bibliographies of selected publications.
      The definition of research results has taken place in consensus procedures on the
      tier of abstracts.Reasons for the unsatisfying reintegration quota are current
      temporary latencies and qualitative deficits of rehabilitation discharge reports,
      unsatisfying communication and cooperation between rehabilitation and company
      doctors, insufficient presence of company doctors, and trust issues between
      rehabilitant and company doctor among other things.The company doctors have an
      objective role as mediator based on their internal knowledge, competences and
      opportunities to influence, and they are awarded with a role as connecting piece
      on setting the course for rehabilitation.Since the currently available data are
      dissatisfactory concerning the medical interfaces in the rehabilitation process,
      despite the high thematically relevance, research activities should absolutely be
      intensified in this field of interest. 

PMID- 25076320
TI  - Microenvironmental factors and extracellular matrix degradation in pancreatic
      cancer.
AB  - Pancreatic cancer is a devastating malady with proclivity for early metastasis,
      accounting for its poor prognosis. Pancreatic ductal adenocarcinoma, the most
      common type of pancreatic malignancy, exhibits an over-expression of several
      growth factors such as epidermal growth factor and transforming growth factor
      beta, which correlate with a decrease in patient survival. These growth factors
      as well as hypoxia-reoxygenation conditions have been shown to increase
      pancreatic tumor cell invasiveness. This review will focus on the signaling
      pathways used by these distinct microenvironmental factors to promote
      extracellular matrix degradation and invasion by pancreatic tumor cells.

PMID- 25076322
TI  - Risk determination for pancreatic cancer.
AB  - Pancreatic cancer represents one of the leading causes of cancer related deaths
      worldwide and constitutes a major public health problem. Despite the advances in
      diagnosis and treatment, the overall five-year survival remains low, thus leading
      the focus of medical research towards the identification and modification of
      potential risk factors. This year, in ASCO Annual Meeting two interesting studies
      were presented. Ghani et al. (abstract #e15183) sought to investigate the effect
      of smoking on chemotherapy response in patients with metastatic pancreatic
      cancer, while Walker et al. (abstract #4117) presented the results of their study
      regarding the effect of statin use in the prevention of pancreatic cancer. Both
      studies concluded to useful results that along with the existing literature may
      further stimulate medical research towards better recognition of risk factors and
      the application of this knowledge in the clinical practice.

PMID- 25076321
TI  - First line treatment for metastatic pancreatic adenocarcinoma: looking for the
      step forward.
AB  - Pancreatic cancer is a lethal disease and its prognosis remains dismal. The
      modest results of existing available treatments in the first line setting reveal
      the need of new therapeutic strategies. In this year's American Society of
      Clinical Oncology (ASCO) Annual Meeting four remarkable studies were presented
      regarding this vulnerable group of patients. The efficacy and toxicity profile of
      gemcitabine plus erlotinib plus capecitabine (Abstract #4122), refametinib plus
      gemcitabine (Abstract #4025), gemcitabine plus docetaxel plus capecitabine plus
      cisplatin (Abstract #4135) were examined and the predictive value of a biomarker
      panel testing response to gemcitabine with or without the addition of erlotinib
      (Abstract #4133) was also presented.

PMID- 25076323
TI  - Thromboembolism and pancreatic cancer.
AB  - Venous thromboembolism (VTE) is a frequent event in the clinical course of
      patients with exocrine pancreatic cancer; studies have been designed to evaluate
      the role of prophylactic anticoagulation in this ominous disease. Searching for
      the molecular basis of thrombosis in cancer, Bozkurt et al. present in the
      Abstract #e22049 the result of their investigation on the frequency of inherited
      and carcinogenesis-acquired proteins in oncologic patients with and without
      venous thromboembolism. From the bedside, Munoz Martin et al. present in the
      Abstract #e15187 their work on the incidence of venous thromboembolism in
      patients with exocrine pancreatic cancer and the role of the established Khorana
      score in predicting symptomatic and incidental venous thromboembolism. At last,
      Cella et al. in the Abstract #e20625 expand the predictor landscape from the
      Khorana score to other risk factors for venous thromboembolism, refining the
      selection of oncologic patients who can benefit from prophylactic
      anticoagulation.

PMID- 25076324
TI  - The management of gastroenteropancreatic neuroendocrine tumors with somatostatin
      analogues.
AB  - Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of
      malignancies, characterized by varying degrees of biological activity and
      metastatic potential. A common thread between this wide mix of neoplasms has
      remained their sensitivity to hormonal modulation with somatostatin analogues.
      New analogues of somatostatin have been recently introduced and are beginning to
      shape a different picture of how we treat and monitor for response in patients
      with gastroenteropancreatic neuroendocrine tumors. Here we discuss three
      important abstracts presented at the annual meeting of the American Society for
      Clinical Oncology (ASCO) 2014 (#4107, #4108, and #4111) that highlight the
      changing landscape of somatostatin-based therapy. 

PMID- 25076325
TI  - Pharmacogenetics in neuroendocrine tumors of the pancreas.
AB  - Neuroendocrine tumors (NETs) arise from cells distributed throughout the
      endocrine system. Although, NETs are heterogeneous in their behavior, they tend
      to be more aggressive when arising in the pancreas. Pancreatic NET (panNET)
      represents three percent of all primary pancreatic neoplasms. Symptomatic and
      progressive panNETs are generally treated with cytotoxic chemotherapy, whereas
      molecular targeted therapy is used for nonfunctional tumors without aggressive
      features. Pharmacogenetics has increasingly been used recently to better identify
      potential targets for therapy and help select patient-specific therapy. In this
      review, we discuss two abstracts (Abstracts #4113 and #e15169) presented at the
      ASCO Annual Meeting in Chicago this year, outlining the potential role of tumor
      gene and gene product profiling in disease management. We describe what is known
      about the pathogenesis of these tumors, role of decreased gene product expression
      (MGMT, RRM1, MET) and its application in cytotoxic therapy selection, as well as
      genetic mutations that can be used for molecular targeted therapy. With an
      overall shift towards personalized medicine, it has become ever more important to
      identify the molecular signature of a tumor as it appears to dictate the clinical
      behavior and response to therapy.

PMID- 25076326
TI  - KRAS in pancreatic cancer.
AB  - Pancreatic cancer is one of the most feared malignancies. The most common form of
      pancreatic cancer is adenocarcinoma arising from the ductal epithelium. KRAS is
      the most common oncogene that has been found to be mutated. However, targeting
      KRAS directly has been difficult. We do not know a lot about the relationship
      between KRAS and other signaling pathways. At the same time, little is known
      about the non KRAS mutated or wild type (WT) tumors. Most of the data that we
      have as far, as mutational status is concerned, has been obtained from the tumor
      itself and not from metastatic lesions. In this review, we discuss two abstracts
      (Abstracts #e15214 and #e15207) published in conjunction with the 2014 ASCO
      Annual Meeting. These discuss the relationship between KRAS and other signaling
      pathways and the differences between mutated KRAS and WT tumors. The studies
      found low rate of KRAS mutation in cells obtained from ascitic fluid. While the
      studies are small, these are novel findings that are worth exploring further.
      They increase our understanding of the biology of the disease and take us a step
      closer to treating this deadly malignancy.

PMID- 25076327
TI  - Biological identification of ampullary adenocarcinomas.
AB  - Ampullary adenocarcinomas have unique biologic and clinical features that result
      in its improved prognosis versus adenocarcinomas that arise from the distal bile
      ducts and pancreas. However the histological differentiation and identification
      of these tumors is not easily accomplished. Two abstracts at this year's ASCO
      Annual Meeting describe attempts to identify unique methods for distinguishing
      these tumors. Abstract #4141 described a 92 gene RT-PCR assay that was used for
      molecular classification of patients with ampullary adenocarcinomas while
      Abstract #e15175 looked at mutational status of K-ras in patients with these
      tumors. The results of their abstracts will be discussed.

PMID- 25076328
TI  - Biomarkers in pancreatic adenocarcinoma.
AB  - Pancreatic adenocarcinoma is a highly aggressive cancer, with a median patient
      survival of less than one year. Clinically useful biomarkers capable of
      accurately assessing prognosis, as well as response to therapy, are urgently
      needed. At the 2014 ASCO Annual Meeting, Maus et al. (Abstract #e15199) and
      Neuzillet et al. (Abstract #e15200) present data on use of c-met as a prognostic
      biomarker, and Shultz et al. (Abstract #4133) use a multiplex antibody panel to
      identify predictive markers of response to gemcitabine and erlotinib.

PMID- 25076329
TI  - Intraductal papillary mucinous neoplasms of the pancreas (IPMNs): new insights on
      clinical outcomes and malignant progression.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) are cystic tumors of the
      pancreas that can progress into invasive carcinomas. Main duct IPMN is usually
      treated with surgery while branch duct IPMN is surgically resected if it is high
      risk based on certain features of the tumor (mostly radiographic) that do have
      some limitations. Predicting the risk of malignant progression has been lately
      the main focus of research especially that comprehending the molecular
      pathogenesis of the disease has emerged as a valuable means to better understand
      the disease and thus guide disease management. We will present two abstracts from
      the ASCO Annual Meeting. The first compares the clinical outcomes of pancreatic
      ductal carcinoma and IPMN associated cancer, and the second looks at the
      pathogenesis of the disease at the cellular and molecular levels to predict high
      risk disease. 

PMID- 25076330
TI  - Chemotherapy and metformin in pancreatic adenocarcinoma and neuroendocrine
      tumors.
AB  - Pancreatic cancer, despite being a relatively less commonly occurring cancer is
      among the deadliest ones, leading to a grave prognosis. Surgery stands as the
      mainstay of treatment of pancreatic cancer but is an option in less than 15%
      patients owing to the late presentation of the tumor. Chemotherapy offers an
      important part of treatment but can adversely affect the quality of life because
      of devastating side effects and has limited survival benefit. Unavailability of
      effective and less toxic treatment options for pancreatic cancer has prompted the
      search for new treatment strategies. One such drug being considered for its
      potential anti-neoplastic role is the time-tested and widely used oral
      hypoglycemic drug, metformin. Metformin is proposed to target metabolic pathways
      involved in tumorigenesis, specifically the AMPK-mTOR complex. Epidemiological
      evidence is mounting in favor of its role in various cancers both for treatment
      and prophylaxis. Herein, we aim to summarize the epidemiological data on
      metformin as a potential anti-cancer drug in various cancers followed by a look
      at some of the abstracts relating to this topic that were presented at the
      American Society of Clinical Oncology (ASCO) Annual Meeting 2014. 

PMID- 25076331
TI  - Quality of life in patients with pancreatic cancer.
AB  - QOL is highly affected in individuals suffering from pancreatic cancer. One
      parameter that influences negatively QOL in these patients is cancer -cachexia
      syndrome. During the ASCO Annual Meeting 2014, one abstract focusing on cancer
      cachexia syndrome (Abstract #15208) emphasized the fact that cachexia is under
      diagnosed even in patients with pancreatic cancer who constitute a high-risk
      group for presenting this syndrome. In addition the abstract raises concerns
      about the benefit of the use of dronabinol and megestrol acetate in treating the
      cachexia syndrome in this group of patients. Another important factor that
      determines QOL in pancreatic cancer patients is surgical procedures
      pancreatectomies that these patients may undergo. A very interesting abstract
      presented also at the ASCO Annual Meeting 2014 (Abstract #15234) explores the
      benefit of using pasireotide perioperative in ameliorating QOL of patients who
      had surgical intervention.

PMID- 25076332
TI  - Diabetes and pancreatic cancer.
AB  - Research suggests a possible link between type 2 diabetes and several
      malignancies. Animal models have shown that hyperinsulinemic state underlying
      diabetes promotes tumor formation through stimulation of insulin-IGF-1 pathway; a
      possible role of inflammation is also proposed. One such link which has been
      under considerable study for years is that between diabetes and pancreatic
      cancer. Although epidemiological evidence points towards a reciprocal link
      between the two, the cause-effect relationship still remains unclear. This link
      was the subject of a large German epidemiological study presented at the American
      Society of Clinical Oncology Annual Meeting 2014 (Abstract #1604), which
      underscored the link between diabetes and some cancers. Schmidt et al. performed
      a retrospective database analysis over a 12 year period and reported an increased
      risk of certain types of cancer in diabetic patients. The most significant
      association (HR 2.17) was found for pancreatic cancer. Given the high mortality
      of pancreatic cancer, prevention through timely screening could play an important
      role in improving prognosis. Older subjects with recent-onset diabetes represent
      a high-risk group and hence are potential targets for pancreatic cancer screening
      thereby enabling its early diagnosis at a curable stage. 

PMID- 25076333
TI  - Elderly patients with pancreatic cancer.
AB  - Pancreatic cancer marked significant increase of incidence during the last
      decades in the elderly population. Despite the certain increase of incidence
      there are no international guidelines for elderly patients who are suffering from
      pancreatic cancer. During the ASCO Annual Meeting 2014, two abstracts focusing on
      elderly patients suffering from different histological types of pancreatic cancer
      were presented. The first retrospective study (Abstract #4119) showed the benefit
      of the systemic treatment on overall survival for elderly patients with stage IV
      pancreatic adenocarcinoma. The second retrospective study (Abstract #4112)
      demonstrates the positive effect of somatostatin analogue (octreotide-LAR)
      treatment on overall survival for elderly patients with neuroendocrine pancreatic
      carcinoma.

PMID- 25076334
TI  - Phase 1 trials in pancreatic cancer.
AB  - Despite many clinical trials over the last two decades since the approval of
      gemcitabine, the survival of patients with pancreatic cancer has improved by a
      few only months. This disappointing reality underlines an urgent need to develop
      more effective drugs or better combinations. A variety of phase I trials were
      presented at the annual meeting of ASCO 2014 focusing on locally advanced and
      metastatic pancreatic cancer. We summarize four abstracts (abstracts #4116,
      #4123, #4026, #4138). 

PMID- 25076335
TI  - Locally advanced unresectable pancreatic cancer.
AB  - Twenty-five percent of patients with pancreatic cancer present with locally
      advanced disease that is unresectable, and the treatment strategy for these
      patients is controversial, with options including chemotherapy alone, concurrent
      chemoradiation, or induction chemotherapy followed by chemoradiation. Abstracts
      presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting
      (#4001, #4126, and #4024) addressed local control, quality of life, and
      prognostic factors associated with current regimens of induction chemotherapy and
      subsequent chemoradiation.

PMID- 25076336
TI  - Radioembolization in the treatment of neuroendocrine tumors of the pancreas.
AB  - Pancreatic neuroendocrine tumors (pNET) are a rare malignancy. Many patients will
      present with metastatic disease most commonly to the liver. Currently the
      standard of care for treatment of liver metastases from neuroendocrine tumors
      (NETs) is surgical resection. However, only few patients are candidates for
      surgical resection and require alternative options. Given the rarity of this
      disease; data regarding treatment options are minimal. In this paper, we will
      review data presented at the annual meeting of ASCO 2014 about the Survival
      following Y90 radioembolization for neuroendocrine tumor liver metastases
      (Abstract #e15166). This abstract shows evidence for survival benefit with the
      use of radioembolization in the treatment of metastatic neuroendocrine tumors to
      the liver. 

PMID- 25076337
TI  - Pharmacogenetics in pancreatic cancer.
AB  - Pancreatic cancer is an aggressive malignancy with a poor overall survival rate.
      Given advances in pharmacogenomics, numerous gene mutations have been identified
      that could be potential targets for drug development. Therefore, future research
      strategies may identify prognostic and predictive markers aiming to improve
      outcome by maximizing efficacy whilst lowering toxicity. In this commentary, we
      summarize several interesting results regarding pancreatic cancer
      pharmacogenetics that have been presented in the 2014 American Society of
      Clinical Oncology (ASCO) Annual Meeting. In particular, we focus on Abstract
      #4124, which investigated the potential predictive role of human equilibrative
      nucleoside transporter 1 (hENT1) in patients treated with adjuvant gemcitabine
      for pancreatic cancer, on Abstract #4125, which examined the tolerability of a
      modified FOLFORINOX study based on UGT1A1*28 genotype guided dosing of IRI in
      patients with advanced pancreatic cancer, and on Abstract #4130, which confirmed
      the predictive role of circulating tumor and invasive cells (CTICs) from patients
      with unresectable pancreatic cancer in second-line chemotherapy treatment
      setting. 

PMID- 25076338
TI  - PARP-inhibitors in BRCA-associated pancreatic cancer.
AB  - Recent data suggests that treating patients with pancreatic cancer that express
      mutations in BRCA1, BRCA2, and PALB2 with chemotherapy which targets the DNA
      repair defect in these cells, such as platinum based therapies or PARPi [poly
      (ADP-ribose) polymerase inhibitor], may be more beneficial in these patients.
      Moreover, further data also indicates the promise of combining PARPi with
      conventional chemotherapy. Authors summarize the data related to PARPi in BRCA
      associated pancreatic cancer that was presented at the annual meeting of ASCO
      2014. Enrolment on a clinical trial for patients who fit these criteria should be
      encouraged.

PMID- 25076339
TI  - Second-line treatment for pancreatic cancer.
AB  - Although standard of care for treatment of pancreatic cancer is established in
      the first line setting, there is limited data to support standard for second line
      chemotherapy for advanced pancreatic cancer. This is starting to change, as new
      studies have shown positive effect on overall survival in the second line
      setting. At the recent ASCO Annual Meeting 2014, several new second-line
      chemotherapy regimens were presented, including ruxolitinib with capecitabine,
      oxaliplatin with 5-FU/leucovorin, metformin plus paclitaxel and gemcitabine plus
      nab-paclitaxel. These abstracts provide exciting new directions for the second
      line treatment of advanced pancreatic cancer that has been refractory to both
      gemcitabine-based regimens as well as non-gemcitabine based regimens.

PMID- 25076340
TI  - Adjuvant treatment for pancreatic cancer.
AB  - Pancreatic cancer is the fourth leading cause of cancer deaths in both men and
      women. Surgical resection has been shown to be the only curable treatment
      available. Unfortunately only 20% of all patients diagnosed with pancreatic
      cancer are surgical candidates due to the aggressive biology of this disease.
      There is no clear consensus on what type of adjuvant therapy should be used for
      patients with pancreatic cancer. Chemoradiation is the favored treatment modality
      by many in the United States while gemcitabine based chemotherapy is favored in
      Europe. Both of these approaches have been shown by large prospective, randomized
      trials to improve disease free intervals and in some studies overall survival.
      The survival of these patients, even status post resection and adjuvant therapy,
      remains poor and therefore the need for alternative adjuvant therapies is needed.
      We will therefore discuss Abstracts #4124, #TPS4162, #4120 and #E15191 in this
      paper which are relevant to the issues described above. 

PMID- 25076341
TI  - Targeted agents in treatment of neuroendocrine tumors of pancreas.
AB  - Neuroendocrine tumors (NET) of the pancreas are uncommon neoplasms that arise
      from the pancreatic islet cells. Surgical resections are being tested, as well as
      multiple chemotherapy agents. Current treatment options for nonresectable disease
      include somatostatin analogs and chemotherapy. New therapies focus on specific
      molecular targets such as sunitinib, angiogenesis inhibitor, that target vascular
      endothelial growth factor receptor (VEGFR) and other growth factor receptors and
      everolimus, an inhibitor of the mammalian target of rapamycin. Functionally based
      medical therapies for NET include somatostatin analogs to control symptoms. The
      2014 annual meeting of American Society of Clinical Oncology (ASCO) brought us
      new insights into the management of pancreatic neuroendocrine tumors. The focus
      of this review will serve to highlight specific Abstracts (#e15160 and #e15161),
      that shed light on new therapeutic options that help target the unique pathways
      of this malignancies.

PMID- 25076342
TI  - Role of neoadjuvant therapy in management of pancreatic cancer.
AB  - Surgery remains the only curative treatment for pancreatic cancer; however,
      majority of patients present with advanced unresectable disease upon diagnosis.
      Treatment of nonmetastatic, locally advanced pancreatic cancer (LAPC) continues
      to require multidisciplinary bimodality or trimodality approach. Neoadjuvant
      therapies have been investigated for LAPC given its established role in other
      solid cancers such as breast cancer, gastric cancer, and rectal cancer. This
      strategy is now moving forward to management of potentially resectable disease as
      well. This meeting highlight focuses on recent updates on neoadjuvant therapy for
      both borderline resectable disease and potentially resectable disease, Abstracts
      #4120, #e15189, #e15226 and #TPS4158 will be discussed.

PMID- 25076343
TI  - Pancreatic cancer: new hopes for early detection and a future screening tool?
AB  - Given the overall poor prognosis of patients with pancreatic cancer, there has
      always been an interest in early screening and primary prevention. An abstract
      presented in ASCO 2014 by Orlowski et al. introduced the potential use of an
      elevated serum procarboxypeptidase A (PCPA) and high ratios of PCPA to free
      carboxypeptidase A (FCPA) in enhancing the diagnostic efficacy of pancreatic
      cancer either alone or with CA19-9 (Abstract #4118). 

PMID- 25076344
TI  - Effect of Livingstone potato (Plectranthus esculentus N.E.Br) on hepatic glucose
      6-phosphophate dehydrogenase activity of streptozotocin induced diabetic rats.
AB  - CONTEXT: To determine the effect of Livingstone potato (Plectranthus esculentus
      N.E.Br) on hepatic G6PD in streptozotocin induced diabetic rats. METHODS: The
      G6PD activities in the liver homogenates of the rats and chemical analysis of the
      test feeds were determined using standard techniques. RESULTS: The diabetic
      control rats had significant elevation (P < 0.05) of their hepatic G6PD
      activities compared with the non-diabetic rats. Intake of the test feed by the
      diabetic rats of group 3, resulted in significant (P<0.05) amelioration of their
      hepatic G6PD activities in comparison with the diabetic control rats. Chemical
      analysis of the test feed revealed that it contained considerable amounts of
      tannins, saponins, alkaloids, antioxidants and their cyanide contents were below
      the toxic level for humans. CONCLUSION: The study shows ameliorative potentials
      of Livingstone potato on the hepatic G6PD activity of diabetic rats which is
      attributed to its antioxidant/polyphenolic constituents.

PMID- 25076345
TI  - Alcohol consumption and pancreatitis mortality in Russia.
AB  - CONTEXT: Pancreatitis is a major public health problem with high associated
      economic costs. The incidence of pancreatitis has increased in many European
      countries in recent decade. Accumulated research and empirical evidence suggests
      that excessive alcohol consumption is a major risk factor for both acute and
      chronic pancreatitis. OBJECTIVE: The aim of this study was to examine the
      aggregate-level relation between the alcohol consumption and pancreatitis
      mortality rates in Russia. METHOD: Age-standardized sex-specific male and female
      pancreatitis mortality data for the period 1970-2005 and data on overall alcohol
      consumption were analyzed by means ARIMA (autoregressive integrated moving
      average) time series analysis. RESULTS: Alcohol consumption was significantly
      associated with both male and female pancreatitis mortality rates: a 1 liter
      increase in overall alcohol consumption would result in a 7.0% increase in the
      male pancreatitis mortality rate and in 2.3% increase in the female mortality
      rate. The results of the analysis suggest that 63.1% of all male pancreatitis
      deaths and 26.8% female deaths in Russia could be attributed to alcohol.
      Conclusions The outcomes of this study provide indirect support for the
      hypothesis that unfavorable mixture of higher overall level of alcohol
      consumption and binge drinking pattern is an important contributor to the
      pancreatitis mortality rate in Russian Federation.

PMID- 25076346
TI  - Effect of pharmaconutrition-supplemented parenteral nutrition for severe acute
      pancreatitis: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the effectiveness of pharmaconutrition-supplemented
      parenteral nutrition (PN) for severe acute pancreatitis (SAP). METHODS: A
      comprehensive search of abstracts was performed in the MEDLINE, OVID, Springer,
      and Cochrane Library database. Published data of randomized clinical trials
      (RCTs) comparing the clinically relevant outcomes of pharmaconutrition
      supplemented PN versus PN for patients with SAP were analyzed. The analyzed
      outcome variables included infection, mortality, intensive care unit (ICU) stay,
      hospital stay, and leukocytes change. Statistical analyses were performed using
      the Cochrane Collaboration's RevMan 5.1 software. RESULTS: Four RCTs published in
      1998 or later were included in this meta-analysis, in which 76 patients with
      pharmaconutrition-supplemented PN and 77 patients with PN. Pharmaconutrition
      supplemented PN showed significantly better results in terms of infection (OR,
      0.42; 95% CI, 0.20-0.91; P =0.03) and leukocytes change (before treated: mean
      different, 0.93; 95% CI, 0.21-1.65; P =0.01; after treated: mean different, 
      0.77; 95% CI, -1.47- -0.08; P =0.03). No significant difference could be found in
      mortality (OR, 0.30; 95% CI, 0.07-1.19; P =0.09), ICU stay (mean different, 
      3.65; 95% CI, -9.39-2.10; P =0.21), and hospital stay (mean different, -1.20; 95%
      CI, -9.89-7.48; P =0.79). CONCLUSIONS: The current meta-analysis indicates that
      pharmaconutrition-supplemented PN only show advantages in infection and
      leukocytes change.

PMID- 25076347
TI  - Interventional radiology procedures after pancreatic resections for pancreatic
      and periampullary diseases.
AB  - CONTEXT: The use of interventional radiology has increased as the first-line
      management of complications after pancreatic resections. METHODS: Patients in
      whom interventional radiology was performed were compared with those in whom
      interventional radiology was not performed as regards type of pancreatic
      resection, diagnosis, postoperative mortality and morbidity, postoperative
      pancreatic fistula postpancreatectomy haemorrhage, bile leakage, reoperation rate
      and length of hospital stay. Our aim was to evaluate the usefulness of
      interventional radiology in the treatment of complications after pancreatic
      resection. RESULTS: One hundred and eighty-two (62.8%) out of 290 patients
      experienced postoperative complications. Interventional radiology procedures were
      performed in 37 cases (20.3%): percutaneous drainage in 28, transhepatic biliary
      drainage in 8 and arterial embolisation in 3 cases. Technical success was
      obtained in all cases and clinical success in 75.7%. Reoperation was avoided in
      86.5%. In patients with major complications, clinically relevant postoperative
      pancreatic fistula and bile leaks as well as those with late postpancreatectomy
      haemorrhage (P=0.030) and patients with postpancreatectomy haemorrhage grade C
      (P=0.029), interventional radiology was used (P<0.001, P<0.001 and P=0.009,
      respectively) significantly more frequently than in the remaining patients. The
      reoperation and mortality rates were similar in the two groups (P=0.885 and
      P=0.100, respectively) while patients treated with interventional radiology
      procedures had a significant longer length of hospital stay than those in the non
      interventional radiology group (37.5 +/- 23.4 vs. 18.7 +/- 11.7 days; P<0.001).
      CONCLUSIONS: Interventional radiology procedures were useful, especially for
      patients with postoperative pancreatic fistulas and bile leaks in whom
      reoperation was very often avoided.

PMID- 25076348
TI  - Pancreatic encephalopathy: an unusual cause of asterixis.
AB  - CONTEXT: Pancreatic encephalopathy is the occurrence of neuropsychiatric
      abnormalities in setting of acute pancreatitis which is not otherwise explained
      by presence of electrolyte abnormities, or organic lesions. The pathogenesis of
      pancreatic encephalopathy is incompletely understood. The clinical presentation
      is variable. CASE REPORT: A 60 year old male, a diabetic for 5 years, was
      admitted with three days of abdominal pain associated with vomiting and
      complicated by altered sensorium for one day. He developed asterixis during the
      course of his hospital stay. Other workup was non-contributory and patient
      improved with supportive management. CONCLUSION: Asterixis has not hitherto been
      reported in pancreatic encephalopathy.

PMID- 25076349
TI  - Intestinal obstruction by a pancreatic bezoar: a case report.
AB  - CONTEXT: Pancreatic pseudocysts are relatively common complications of
      pancreatitis. A pseudocyst can result from an episode of acute pancreatitis,
      exacerbation of chronic pancreatitis, or trauma. Treatment is indicated for
      persistent, symptomatic pseudocysts and in the case of related complications.
      CASE REPORT: We describe the case of a 66-year-old man who referred to our
      department for bowel obstruction caused by a necrotic pancreatic bezoar occurring
      16 days after the patient underwent a jejunal-pseudocyst anastomosis performed to
      treat a post-pancreatitis voluminous pseudocyst obstructing the gastric outlet.
      CONCLUSION: In case of intestinal obstruction after a jejunal-pseudocyst
      anastomosis, pancreatic bezoar should be considered in the armamentarium of the
      differential diagnosis.

PMID- 25076350
TI  - Johanson-Blizzard syndrome: expanding the phenotype of exocrine pancreatic
      insufficiency.
AB  - CONTEXT: Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive syndrome
      characterized by dysmorphic nasal alae, ectodermal abnormalities, exocrine
      pancreatic insufficiency and early growth failure. Most patients are diagnosed by
      clinical criteria prenatally or in early infancy. Nonsense, frame shift and
      splice-site mutations of the ubiquitin ligase gene (UBR1) lead to early loss of
      acinar cells in individuals with JBS. CASE REPORT: We describe a previously
      asymptomatic patient with ectodermal dysplasia presenting with sudden onset
      exocrine pancreatic insufficiency in adolescence. The family reports an identical
      twin brother with similar symptoms. CONCLUSION: This case illustrates that the
      phenotypic variability of pancreatic involvement in JBS may be subtle and may not
      manifest until the second decade of life. We suspect that this mild phenotype
      results from mutations in UBR1 allowing for partial function.

PMID- 25076351
TI  - Natural history of branch-duct intraductal papillary mucinous neoplasms of the
      pancreas: a case report.
AB  - CONTEXT: The natural history of incidental branch-duct intraductal papillary
      mucinous neoplasm of the pancreas is still unknown. CASE REPORT: The case of a 74
      year-old man who had been diagnosed 14 years previously with an incidental branch
      duct intraductal papillary mucinous neoplasm of the pancreatic head, 30 mm in
      size, without mural nodules and dilatation of the main pancreatic duct is herein
      reported. After an exploratory laparotomy at the time of diagnosis (when he was
      60 year-old), the patient was enrolled in a surveillance program. Fourteen years
      after the diagnosis, the cystic lesion showed an increase in size, Wirsung duct
      dilatation and the presence of several mural nodules. A total pancreatectomy was
      performed and a diagnosis of mixed-intraductal papillary mucinous neoplasm
      diffused throughout the entire pancreas with high grade dysplasia, and a micro
      invasive carcinoma (<1 mm) of the pancreatic head was reached. CONCLUSION: The
      present case confirmed that the natural history of branch-duct intraductal
      papillary mucinous neoplasms is unpredictable. Thus, an appropriate surveillance
      program is required for prompt identification of the signs predictive of a
      malignant transformation of branch-duct intraductal papillary mucinous neoplasms.
      In high-volume centers, surgery should seriously be considered in young patients
      who are fit for surgery.

PMID- 25076352
TI  - Clinical observation of macroamylasemia in splenosis due to the posttraumatic
      splenectomy.
AB  - CONTEXT: Article analyzes current data on macroamylasemia and splenosis, their
      etiology and diagnostics in particular. CASE REPORT: Authors presented their own
      clinical observation of a young woman who was diagnosed to have macroamylasemia
      on the background of splenosis due to the splenectomy after blunt abdominal
      injury. CONCLUSION: This is the first time such a combination of macroamylasemia
      on the background of splenosis has been described in the literature.

PMID- 25076353
TI  - Pancreatic hemolymphangioma.
AB  - CONTEXT: Hemolymphangioma of pancreas is a tumor has its origins on vascular and
      lymphatic vessels malformation. At this time, only eight cases have been reported
      (PubMed). CASE REPORT: A 52-year-old woman with history of abdominal pain and
      early satiety was admitted to our external consultation. Laboratory data were
      normal. CT initially showed a high vascularized solid tumor, apparently arising
      from the right hepatic lobe, and it was considered to be a hemangioma. Two
      sessions of CT guided embolizations were performed. Control CT scan revealed a
      reduction in tumor's size and location confined to pancreatic head. With this
      diagnosis studies and suspicion of neoplastic tumor, it was performed a pylorus
      preserving pancreatoduodenectomy. Pathology report was to be a pancreatic head
      hemolymphangioma. CONCLUSION: Diagnosis and management of cystic pancreatic
      tumors can be challenging. Cystectomy or even surgical procedures as
      pancreatoduodenectomy should be performed when is possible. We report a case of
      pancreatic hemolymphangioma, a benign cystic tumor with a rare incidence.

PMID- 25076354
TI  - Isolated primary pancreatic Wegener's granulomatosis: report of two cases.
AB  - CONTEXT: Chronic inflammatory vasculitis, namely Wegener's granulomatosis, is an
      autoimmune disease predominantly affecting the respiratory tract and rarely the
      mucosa of the upper or lower gastrointestinal tract. We report two cases of
      isolated pancreatic manifestation of Wegener's granulomatosis, mimicking a tumor.
      CASE REPORTS: Two patients, a 57-year-old man and a 68-year-old woman, presented
      with isolated lesions thought to be pancreatic adenocarcinoma and both underwent
      surgical resection. On pathology, the lesions were found to be a granulomatous
      vasculitis and were considered to represent isolated pancreatic Wegener's
      granulomatosis, in the absence of other clinical features of the disease.
      CONCLUSIONS: Benign diseases such as Tuberculosis may mimic pancreatic tumours
      diagnosed on cross-sectional imaging. Wegener's granulomatosis should be included
      in the differential diagnosis of an isolated pancreatic mass, in the absence of
      other cardinal symptoms for malignancy, due to the extensive surgery and risks
      involved in resection of pancreas.

PMID- 25076355
TI  - Dynamic contrast-enhanced MRI findings of acute pancreatitis in ectopic
      pancreatic tissue: case report and review of the literature.
AB  - CONTEXT: Acute pancreatitis in ectopic pancreatic tissue is an uncommon cause of
      acute abdominal pain and can be difficult to diagnose on imaging. Our aim is to
      raise awareness and aid in the diagnosis of this entity by highlighting helpful
      dynamic contrast-enhanced MRI imaging findings. CASE REPORT: We report a 51-year
      old man with acute onset epigastric pain presented to ER. With the presence of
      elevated serum lipase, the clinical diagnosis of acute pancreatitis was made.
      Contrast enhanced CT demonstrated normal pancreas and a focal mass at the
      duodenojejunal flexure, mimicked a neoplasm. Subsequent dynamic contrast enhanced
      MR images demonstrated enhancement pattern of the lesion similar to the native
      pancreatic tissue enhancement, a finding raised the possibility of acute
      pancreatitis in ectopic pancreatic tissue, but tumor was not excluded. Finally,
      patient undergone surgical bowel resection including the suspected mass that was
      proved as an ectopic pancreatic tissue on microscopic examination. CONCLUSION: We
      concluded that findings on dynamic contrast enhanced MR imaging can be
      characteristic and diagnostic of acute pancreatitis in ectopic pancreatic tissue
      in the appropriate clinical setting.

PMID- 25076356
TI  - A case of pancreatic cancer as a recurrence of intraductal papillary mucinous
      neoplasm following surgical resection.

PMID- 25076357
TI  - Tumoral bacillary angiomatosis in a child with human immunodeficiency virus.

PMID- 25076358
TI  - Methoxy functionalisation: exerting synthetic control of the supramolecular and
      electronic structure of nitrogen-doped nanographenes.
AB  - We describe a series of functionalized N-containing heterosuperbenzenes, created
      with a view to investigating the strategic role of methoxy substituents in (i)
      promoting cyclodehydrogenation and (ii) tuning the electronic properties and
      (iii) the supramolecular order in the resultant fused products. 

PMID- 25076359
TI  - Comparison of clinical characteristics and outcomes in patients with left bundle
      branch block versus ST-elevation myocardial infarction referred for primary
      percutaneous coronary intervention.
AB  - AIMS: Recent studies have suggested that a low proportion of patients presenting
      with left bundle branch block (LBBB) require emergency intervention. In this
      study, we have compared baseline clinical characteristics, angiographic findings
      and subsequent outcomes in patients with LBBB versus ST-elevation myocardial
      infarction (STEMI) referred to our tertiary centre for primary percutaneous
      coronary intervention (PCI). METHODS AND RESULTS: A large retrospective
      observational study was performed involving 1875 consecutive patients presenting
      to our single tertiary cardiac centre for primary PCI over a 27-month period.
      Patients presenting with LBBB (n=155, 8.3%) were significantly older (P<0.0001)
      and were more likely to be female (P<0.0001) and have a prior history of
      myocardial infarction (P<0.0001) or coronary artery bypass graft surgery
      (P=0.005). Rates of acute occlusion (12.2 vs. 63%; P<0.0001) and PCI (26 vs. 83%;
      P<0.0001) were significantly lower in LBBB patients compared with STEMI patients.
      Although the 30-day mortality was similar, overall mortality during the 2 years
      of follow-up was significantly higher in the LBBB group compared with the STEMI
      group (27.8 vs. 13.9%; P=0.023). CONCLUSION: The incidence of an acutely occluded
      vessel is low in LBBB when compared with STEMI, but the long-term outcome is
      significantly worse. Patients with LBBB referred for primary PCI need better risk
      stratification, and further work is needed to identify potential diagnostic and
      management strategies.

PMID- 25076361
TI  - A comparison of laparoscopic vs open hepatectomy: good try, but we still have
      selection bias.

PMID- 25076360
TI  - Switching types of drug-eluting stents does not prevent repeated in-stent
      restenosis in patients with coronary drug-eluting stent restenosis.
AB  - OBJECTIVES: We treated patients experiencing drug-eluting stent (DES) restenosis
      with plain old balloon angioplasty (POBA), implantation of the same type of DES
      [homogeneous drug-eluting stent (HOMO-DES)], or implantation of a different type
      of DES [heterogeneous drug-eluting stent (HETERO-DES)], and compared the efficacy
      and safety of these procedures for the prevention of repeated in-stent restenosis
      (ISR). BACKGROUND: In patients with de-novo coronary lesions, DES implantation is
      associated with a markedly reduced restenosis rate as compared with that
      associated with a bare metal stent and POBA. However, the optimal management
      strategy for patients with DES ISR remains unknown. PATIENTS AND METHODS: We
      identified 191 consecutive DES ISR lesions from 183 patients who required
      clinically driven revascularization and divided them into three groups according
      to the treatment: 38 lesions were treated with POBA, 38 with HOMO-DES, and 115
      with HETERO-DES. RESULTS: The incidence of target lesion revascularization (TLR)
      was 42.1% (16/38), 15.8% (6/38), and 16.5% (19/115) in the POBA, HOMO-DES, and
      HETERO-DES groups (POBA vs. HOMO, HETERO-DES; P=0.002, respectively).
      Multivariate analysis indicated that diabetes [odds ratio (OR), 3.4],
      hemodialysis (OR, 7.74), nonfocal ISR patterns (OR, 3.35), previous myocardial
      infarction (OR, 3.26), and POBA (OR, 8.84) were independent predictors of TLR.
      CONCLUSION: A strategy involving repeated DES implantation was superior to POBA
      for preventing recurrent restenosis. Treatment with a different type or
      generation of DES does not appear to reduce the incidence of TLR. Moreover, we
      identified certain useful factors for facilitating appropriate and early triage
      in the patients with repeated DES ISR.

PMID- 25076363
TI  - Anterior segment optical coherence tomography in acute anterior uveitis.
AB  - PURPOSE: To analyze the corneal thickness and anterior chamber (AC) angle using
      anterior segment optical coherence tomography (AS-OCT) in patients with acute
      anterior uveitis (AAU). METHODS: Twenty two patients (24 eyes) were included. All
      patients underwent complete ophthalmological examination, applanation tonometry
      and AS-OCT at diagnosis and fifteen days after treatment. RESULTS: Average
      corneal thickness before treatment was 564.2 +/- 44.2 um, 580.0 +/- 44.3 um and
      580.1 +/- 2.9 um, respectively in central, pericentral and paracentral cornea.
      Fifteen days after treatment a significant decrease of corneal thickness was
      observed, with 529.5 +/- 33.1 um (p=0.0091) and 542.6 +/- 33.6 um (p=0.0068),
      respectively in central and pericentral cornea; paracentral corneal thickness
      (557.8 +/- 35.3 um) thinning did not reach statistical significance (p=0.1253).
      There was no significant change in temporal AC angle between visits, 44.3 +/-
      14.4 degrees before treatment and 44.7 +/- 14.7 degrees fifteen days after
      (p=0.9343), and mean intraocular pressure, 10.8 +/- 4.5 mmHg before treatment and
      12.3 +/- 3.0 mmHg fifteen days after (p=0.1874). CONCLUSION: In the studied
      group, AS-OCT detected a decrease of corneal thickness after AAU treatment.
      Temporal AC angle and intraocular pressure did not change during the studied
      period.

PMID- 25076362
TI  - mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice
      via induction of GLUT2.
AB  - BACKGROUND & AIMS: Microsomal prostaglandin E synthase-2 (mPGES-2) deletion does
      not influence in vivo PGE2 production and the function of this enzyme remains
      elusive. The present study was undertaken to investigate the role of mPGES-2 in
      streptozotocin (STZ)-induced type-1 diabetes and organ injuries. METHODS: mPGES-2
      wild type (WT) and knockout (KO) mice were treated by a single intraperitoneal
      injection of STZ at the dose of 120 mg/kg to induce type-1 diabetes.
      Subsequently, glycemic status and organ injuries were evaluated. RESULTS:
      Following 4 days of STZ administration, mPGES-2 KO mice exhibited severe
      lethality in contrast to the normal phenotype observed in WT control mice. In a
      separate experiment, the analysis was performed at day 3 of the STZ treatment in
      order to avoid lethality. Blood glucose levels were similar between STZ-treated
      KO and WT mice. However, the livers of KO mice were yellowish with severe global
      hepatic steatosis, in parallel with markedly elevated liver enzymes and
      remarkable stomach expansion. However, the morphology of the other organs was
      largely normal. The STZ-treated KO mice displayed extensive hepatocyte apoptosis
      compared with WT mice in parallel with markedly enhanced inflammation and
      oxidative stress. More interestingly, a liver-specific 50% upregulation of GLUT2
      was found in the KO mice accompanied with a markedly enhanced STZ accumulation
      and this induction of GLUT2 was likely to be associated with the insulin/SREBP-1c
      pathway. Primary cultured hepatocytes of KO mice exhibited an increased
      sensitivity to STZ-induced injury and higher cellular STZ content, which was
      markedly blunted by the selective GLUT2 inhibitor phloretin. CONCLUSIONS: mPGES-2
      deletion enhanced STZ-induced liver toxicity possibly via GLUT2-mediated STZ
      uptake, independently of diabetes mellitus.

PMID- 25076365
TI  - Influence of head posture on the visual acuity of children with nystagmus.
AB  - PURPOSE: Evaluate the relationship between the postural alignment of the head and
      possible interference in the view of children. METHODS: We evaluated 11 children
      between 2 and 7 years of age of both sexes, with the visually impaired, who had
      nystagmus and head lock position. The test Lea Grating Acuity Test(r) was used to
      collect measurements of visual acuity. This applied on two occasions: with and
      without postural alignment of the head. For reliability of the postural alignment
      of the head, the slopes were measured by Fisiologic(r) software. RESULTS: The
      children had a poorer performance after physiological postural alignment. This
      poor performance is possible due to loss of position lock nystagmus to gain
      postural alignment, said to be ideal. Postural compensations were observed, and
      sharply increased eyestrain. CONCLUSION: The pursuit of traditional postural
      alignment affect the visual response of children with visual impairments.

PMID- 25076364
TI  - Efficacy and safety of subconjunctival bevacizumab for recurrent pterygium.
AB  - PURPOSE: To evaluate the clinical outcome(s) and complication(s) of
      subconjunctival bevacizumab treatment in patients with recurrent pterygium.
      METHODS: This prospective case series included patients who had undergone
      pterygium surgery and were diagnosed with recurrent pterygium. All patients
      received one subconjunctival injection of 0.5 mL of bevacizumab (2.5 mg/0.1 mL).
      The main outcome was the change in size and clinical appearance. The clinical
      appearance of the pterygium was graded according to Tan and colleagues. The
      horizontal size of the pterygium (from limbus to apex) was recorded from baseline
      to 2 months after injection. Treatment-related complications and adverse events
      were reported. RESULTS: We included 36 eyes of 36 patients (18 males) with a mean
      age of 58.75 +/- 10.98 years. Totally, 30.6% patients developed recurrent
      pterygium in both eyes (only the worst eye was treated), with 47.2% developing it
      in the left eye and 22.2% in the right eye. More than half the patients (58.3%)
      had a family history of pterygium. There was a significant difference in the size
      of pterygium at different intervals (P<0.05). Approximately two-thirds (66.7%) of
      patients presented with hyposphagma on the 2nd day after subconjunctival
      application; this value decreased to 30.6% by day 7 and to 0% at 1 month. Most
      patients (69.4%) exhibited amelioration of irritative symptoms within 2 days,
      88.9% after 7 days, and 97.2% after 1 month. CONCLUSIONS: Subconjunctival
      bevacizumab injection is useful for the management of patients with recurrent
      pterygium, with no significant local or systemic adverse effects.

PMID- 25076366
TI  - Life quality assessment of patients after phacoemulsification or extracapsular
      cataract extraction.
AB  - PURPOSE: To study the quality of life, treatment outcomes, and satisfaction in
      patients who have undergone cataract surgery Methods: This comparative case
      series study was conducted at the Ophthalmology Service of the Bettina Ferro de
      Souza University Hospital, Belem, Para, Brazil. Totally, 60 patients with
      cataract were included; 50% underwent conventional extracapsular cataract
      extraction (ECEE) and 50% underwent cataract extraction by phacoemulsification
      (PHACO). Patients were interviewed using the Visual Function 14 (VF-14)
      questionnaire to determine the quality of life before and 30 days after surgery.
      The results of ophthalmological examination were recorded in the patients' files
      and were available throughout this study. One-way ANOVA, Tukey's post-hoc
      comparison, and the sign test were used for statistical analyses. RESULTS: The
      mean VF-14 satisfaction index was 38.0 and 89.4 before and after surgery,
      respectively, for the ECEE group and 47.0 and 94.1, respectively, for the PHACO
      group. The improvement in patient quality of life after surgery was significant
      in both groups (p<0.0001), with a similar amount of improvement in both groups.
      CONCLUSIONS: The observed improvement in quality of life was significant
      (p<0.0001) and directly related to patient satisfaction with surgical outcomes,
      which was also significant (p<0.0001) as assessed using the VF-14. Satisfaction
      and quality of life are individual factors; consequently, patient responses to
      questions regarding improvements in the ability to perform each activity are
      subjective and depend uniquely on individual perception.

PMID- 25076367
TI  - Assessment of anterior and posterior corneal indices using two Scheimpflug
      analyzers.
AB  - PURPOSE: To assess the agreement between the elevation and curvature measurements
      of the anterior and posterior corneal surfaces obtained using the Galilei Dual
      Scheimpflug Analyzer and those obtained using the Pentacam single Scheimpflug
      system. METHODS: This prospective, noninterventional, diagnostic study was
      conducted at the Department of Ophthalmology at the American University of Beirut
      (Medical Center) and included 60 eyes of 60 consecutive patients. Measurements
      were obtained using 2 different Scheimpflug analyzers (Galilei and Pentacam). The
      best-fit sphere was set at 8 mm in both machines. Pachymetry (CCT), anterior
      elevation (AE) and posterior elevation (PE), and curvature were assessed.
      Pearson's correlation coefficients, comparison of means, and Bland-Altman plots
      were used to evaluate agreement between the 2 systems. RESULTS: The average CCT
      (at the corneal apex) was 533 +/- 35 um and 532 +/- 37 um (p=0.980), the average
      central AE was 1.25 +/- 3.95 um and 2.29 +/- 5.28 um (p=0.964), and the average
      central PE was 4.19 +/- 8.18 um and 5.42 +/- 14.05 (p=0.956) um with the Galilei
      and Pentacam, respectively. CONCLUSION: The Scheimpflug analyzers correlated well
      in the assessment of pachymetry, elevation, and curvature.

PMID- 25076368
TI  - Translation and validation of Convergence Insufficiency Symptom Survey (CISS) to
      Portuguese - psychometric results.
AB  - PURPOSE: Translate and adapt the Convergence Insuficiency Symptom Survey (CISS)
      questionnaire to the Portuguese language and culture and assess the psychometric
      properties of the translated questionnaire (CISSvp). METHODS: The CISS
      questionnaire was adapted according to the methodology recommended by some
      authors. The process involved two translations and back-translations performed by
      independent evaluators, evaluation of these versions, preparation of a synthesis
      version and its pre-test. The final version (CISSvp) was applied in 70 patients
      (21.79 +/- 2.42 years) students in higher education, and at two different times,
      by two observers, to assess its reliability. RESULTS: The results showed good
      internal consistency of the CISSvp (Cronbach's alpha - alpha=0.893). The test re
      test revealed an average of the differences between the first and second
      evaluation of 0.75 points (SD +/- 3.53), which indicates a minimum bias between
      the two administrations. The interrater reliability assessed by intraclass
      correlation coefficient ranged from 0.880 to 0.952, revealing that the CISSvp
      represents an appropriate tool for measuring the visual discomfort associated
      with near vision tasks with a high level of reproducibility. CONCLUSIONS: The
      CISS Portuguese version, showed good psychometric properties and has been sown to
      be applicable to the Portuguese population, to quantify the visual discomfort
      associated with near vision, in higher education students.

PMID- 25076369
TI  - Complexities and challenges of surgical data collection from cataract patients:
      comparison of cataract surgery rates between 2001 and 2008 in all provinces of
      Argentina.
AB  - PURPOSE: To compare the cataract surgical rate (CSR) in 2001 with that in 2008 in
      all Argentinean provinces using current reporting methods and verify the accuracy
      of CSRs by cross-checking these methods with the number of sold intraocular
      lenses (IOLs) within the country. METHODS: A longitudinal study including public
      and private set-ups was conducted, and it included 40 ophthalmologists from 22
      provinces who provided cataract surgery data for 2001 and 2008. Other data were
      obtained from the Ministry of Health. Estimates were cross-checked against the
      market data for sold intraocular lens (IOLs) in 2008 and 2010. RESULTS: The
      number of cataract surgeries increased 2.7-fold, from 62,739 in 2001 to 169,762
      in 2008, with increases in every province except Mendoza. Although the population
      also increased by 9.4% during the same time period, the apparent CSR jumped from
      1,744 to 4,313 per million population. The number of IOLs sold in Argentina in
      2008 was 186,652, suggesting that the number of cataract surgeries performed was
      slightly greater than anticipated. Cross-checks with other countries using IOL
      sales data did not show discrepancies when compared with previously reported
      CSRs. CONCLUSIONS: Although the CSR in Argentina increased considerably from 2001
      to 2008 for several reasons, the main reason was that thorough cross-checking
      between the number of surgeries reported and the number of IOLs sold revealed
      that the number of surgeries performed annually were being underestimated as a
      result of incomplete reporting by private practitioners. Furthermore, the
      presence of multiple societies of ophthalmology in the country complicated the
      process of obtaining accurate data.

PMID- 25076370
TI  - Clinical and epidemiological characteristics of patients with uveitis in an
      emergency eye care center in Brazil.
AB  - PURPOSE: To analyze the clinical and epidemiological characteristics of patients
      with uveitis in an emergency eye care center. METHODS: We conducted a
      prospective, observational study of patients with active uveitis admitted between
      May 2012 and July 2012 to an emergency eye care center. RESULTS: The majority of
      patients were male (63.2%), with a mean age of 43.2 years; 66.2% patients were of
      mixed ethnicity, 22.5% were Caucasian, and 11.3% were black. Anterior uveitis was
      observed in 70.1% patients, posterior uveitis in 26.5%, and panuveitis in 3.4%;
      no patient was diagnosed with intermediate uveitis. All patients had a sudden and
      acute presentation. The most frequent symptoms were ocular pain (76.9%), redness
      (59.8%), and visual blurring (46.2%). The majority of patients had unilateral
      disease (94.9%) with a mean symptom duration of 6.2 days. Diffuse and anterior
      uveitis were associated with ocular pain (p<0.001). Scotomata and floaters were
      more frequent in patients with posterior uveitis (p=0.003 and p=0.016,
      respectively). Patients with anterior uveitis presented with better visual acuity
      (p=0.025). Granulomatous keratotic precipitates were more frequent in patients
      with posterior uveitis (p=0.038). An etiological diagnosis based on the
      evaluation at the emergency center was made in 45 patients (38.5%). CONCLUSIONS:
      Acute anterior uveitis was the most frequent form of uveitis. Initial patient
      evaluation provided sufficient information for deciding primary therapy and aided
      in arriving at an etiological diagnosis in a considerable number of patients.

PMID- 25076371
TI  - Comparative study of visual functions in premature pre-school children with and
      without retinopathy of prematurity.
AB  - PURPOSE: Observe whether there are differences in visual functions among
      premature infants with treated retinopathy of prematurity (ROP) in relation to
      preterm infants with ROP and spontaneous regression; and among these two groups
      with ROP and the control group without ROP. METHODS: Cross-sectional
      observational no blind study. Premature infants were born between 06/199206/2006
      and were exam between 06/200912/2010; registered in data of Hospital de Olhos
      Sandalla Amin Ghanem; with gestational age less than or equal to 32 weeks and
      1,599 g born weigh; without ROP and ROP stages II or III, in one of the eyes,
      with spontaneous regression or with treatment; at least three visits during the
      selection period at maximum 6 months in the first exam and minimum 4 years of age
      in reassessment (chronological age) were include. Premature that did not respond
      or were not located for reassessment and those that did not have conditions to do
      the exams were exclude. Study's groups: G1 ROP posttreatment; G2ROP post
      spontaneous regression; G3 without ROP (control). Visual function evaluated with
      visual acuity (VA), contrast sensitivity test (CST), color test (CT), eye
      movement, stereopsis. RESULTS: Overall, there were 24 premature infants and 48
      eyes. Normal VA: 64.28% (G1), 87.5% (G2) and 100% (G3); Normal CST: 66.67% (G1),
      100% (G2) and 55.56% (G3); Normal Ishihara CT: 100% (G1 and G2) and 86% (G3);
      Normal Farnsworth CT: 20% (G1), 75% (G2) and 50% (G3). Normal stereoacuity: 0.00%
      (G1); 25% (G2) and 3.5% (G3). Strabismus: 37% (G2), 0.00% (G1 and G3). The
      prevalent tendency for lower response in CST and CT between the premature
      children in group G3 and Farnsworth color test in G1 is a curious result of this
      work and more study is necessary about these visual functions in older premature
      children. CONCLUSION: The visual functions showed no statistically significant
      difference among the groups studied.

PMID- 25076372
TI  - Treatment of astigmatism during phacoemulsification.
AB  - PURPOSE: To compare the effectiveness of limbal relaxing incisions (LRI) with
      that of toric intraocular lens (IOL) implantation for the treatment of
      astigmatism during phacoemulsification using nonvectorial (predictability,
      safety, and efficacy) and vectorial analyses. METHODS: This longitudinal
      observational case series assessed 62 eyes of 31 consecutive cataract patients
      with preoperative corneal astigmatism of 0.75-2.50 diopters (D) in both eyes.
      Patients were randomly assigned to 2 groups: a toric IOL group, which received
      toric IOLs in both eyes, and an LRI group, which received spherical IOLs
      associated with LRI placement in both eyes. All patients were evaluated at 1, 3,
      and 6 months after surgery, when refractive astigmatism analysis was performed
      using both nonvectorial and Alpins vectorial methods. Outcomes were assessed
      within each group and compared between groups. RESULTS: The proportion of eyes
      within +/-0.50 D of the intended correction at 3 and 6 months after surgery was
      75% and 71.88%, respectively, in the LRI group and 40% and 66.67%, respectively,
      in the toric IOL group. In the remaining period, the proportion was greater in
      the toric IOL group. The safety index showed no difference at any time point. The
      efficacy index at 1 and 3 months after surgery was significantly higher in the
      toric IOL group (0.43 and 0.44, respectively) than in the LRI group (0.31 and
      0.36, respectively). At 6 months after surgery, the status of eyes in the LRI
      group was as follows: 53.13% were undercorrected, 43.74% achieved the intended
      correction, and 3.13% were overcorrected. In the toric IOL group, 16.76% eyes
      were undercorrected, 76.67% achieved the intended correction, and 6.67% were
      overcorrected. The success rates for astigmatic surgery, astigmatism reduction at
      the intended axis, and astigmatism corrected were 43%, 62%, and 64%,
      respectively, in the LRI group and 57%, 81%, and 94%, respectively, in the toric
      IOL group. CONCLUSIONS: Our results suggest that the use of toric IOLs may be
      advantageous over the use of LRIs for the treatment of astigmatism during
      phacoemulsification. Although such advantages seem subtle in nonvectorial
      analyses, they are highlighted in vectorial analyses.

PMID- 25076373
TI  - Ophthalmic evaluation, treatment, and follow-up of two cases of incontinentia
      pigmenti.
AB  - Incontinentia pigmenti (IP) is an X-linked dominant disorder affecting the skin,
      teeth, eyes, and central nervous system. Ocular changes are common and may lead
      to severe vision loss. We report on the ocular manifestations in two young girls
      with IP, with emphasis on the asymmetry of this condition in both eyes and
      associated retinal problems. The outcomes of laser treatment of the ischemic
      peripheral retina were good and resulted in stability of vision.

PMID- 25076374
TI  - Direct cyclopexy surgery for post-traumatic cyclodialysis with persistent
      hypotony: ultrasound biomicroscopic evaluation.
AB  - Cyclodialysis is a relatively rare condition usually caused by ocular injury;
      however, it can also be caused iatrogenically during intraocular surgery.
      Hypotony maculopathy is the most important complication and the primary reason
      for visual loss. Clinical diagnosis using gonioscopy may be difficult, and
      ultrasound biomicroscopy (UBM) can be an alternative. There are different kinds
      of treatments, and the optimal one remains controversial. Here we describe a case
      of traumatic cyclodialysis with persistent ocular hypotony treated by direct
      cyclopexy, as illustrated by UBM performed before and after surgery. 

PMID- 25076375
TI  - Case report of a metachronous multiple tumor: mantle cell lymphoma in the orbital
      region associated with epithelial malignancies at other sites.
AB  - Here we report the case of a 73-year-old man who was diagnosed with metachronous,
      multiple primary tumors with non-Hodgkin B-cell mantle cell lymphoma involving
      the orbit on the basis of biopsy and immunohistochemistry in 2012. The patient
      had been diagnosed with non-Hodgkin small cell lymphoma and basal cell skin
      carcinoma in 2010 and intestinal adenocarcinoma with metastasis to the regional
      lymph nodes in 2011, thus representing a typical case of metachronous, multiple
      primary tumors. Mantle cell lymphoma is a rare disease and its prognosis is quite
      poor, particularly when it is associated with other metachronous malignancies.
      Therefore, physicians should consider mantle cell lymphoma as a differential
      diagnosis for neoplasms of the orbit. 

PMID- 25076376
TI  - Amelanotic corneally displaced malignant conjunctival melanoma: a case report
      evaluated with impression cytology.
AB  - Here we describe the case of a 65-year-old Caucasian female who presented with an
      amelanotic malignant conjunctival melanoma and highlight the clinical and
      pathological features of this rare entity that displayed exclusive corneal
      invasive growth without evidence of conjunctival tumors other than primary
      acquired melanosis. Impression cytology aided in the initial diagnosis. The
      patient underwent surgical treatment. Histopathology and immunohistochemistry
      revealed an invasive amelanotic melanoma limited to the cornea and exhibiting S
      100, Melan A, and HMB-45 positivity. The absence of pigmentation delayed early
      clinical detection and treatment. Awareness of this nonpigmented melanoma is
      important for early recognition and appropriate management. 

PMID- 25076377
TI  - Finite element modelling of cornea mechanics: a review.
AB  - The cornea is a transparent tissue in front of the eye that refracts light and
      facilitates vision. A slight change in the geometry of the cornea remarkably
      affects the optical power. Because of this sensitivity, biomechanical study of
      the cornea can reveal much about its performance and function. In vivo and in
      vitro studies have been conducted to investigate the mechanics of the cornea and
      determine its characteristics. Numerical techniques such as the finite element
      method (FEM) have been extensively implemented as effective and noninvasive
      methods for analyzing corneal mechanics and possible disorders. This article
      reviews the use of FEM for assessing the mechanical behavior of the cornea.
      Different applications of FEM in corneal disease studies, surgical predictions,
      impact simulations, and clinical applications have been reviewed. Some
      suggestions for the future of this type of modeling in the area of corneal
      mechanics are also discussed. 

PMID- 25076378
TI  - Restoration of accommodation: new perspectives.

PMID- 25076379
TI  - Structural manipulation on the catecholic fragment of dopamine D(1) receptor
      agonist 1-phenyl-N-methyl-benzazepines.
AB  - A series of new benzazepines with modification on the catecholic fragment were
      designed. The 8-hydroxyl group, other than the 7-hydroxyl was confirmed crucial
      to the interaction with the dopamine D1 receptor. Subsequent replacement of the 7
      hydroxyl with benzylamino groups was found tolerable. 7-(m
      Chlorophenyl)methylamino- and 7-(m- or o-tolyl)methylamino-substituted
      benzazepines 13b-d displayed Ki values of 270-370 nM at the D1 receptor, which
      were slightly more potent than that of parent compound 1. In addition, 7
      (arylmethyl)amino-benzazepines 13a-c were found possessing high binding
      affinities less than 10 nM at the 5-HT2A receptor. Among them, the non
      substituted 7-benzylamino analogue 13a was the most potent showing a Ki values of
      4.5 nM at the 5-HT2A receptor and a 5-HT2A/D1 selectivity of 147. 

PMID- 25076380
TI  - Use of pantothenate as a metabolic switch increases the genetic stability of
      farnesene producing Saccharomyces cerevisiae.
AB  - We observed that removing pantothenate (vitamin B5), a precursor to co-enzyme A,
      from the growth medium of Saccharomyces cerevisiae engineered to produce beta
      farnesene reduced the strain's farnesene flux by 70%, but increased its
      viability, growth rate and biomass yield. Conversely, the growth rate and biomass
      yield of wild-type yeast were reduced. Cultivation in media lacking pantothenate
      eliminates the growth advantage of low-producing mutants, leading to improved
      production upon scale-up to lab-scale bioreactor testing. An omics investigation
      revealed that when exogenous pantothenate levels are limited, acyl-CoA
      metabolites decrease, beta-oxidation decreases from unexpectedly high levels in
      the farnesene producer, and sterol and fatty acid synthesis likely limits the
      growth rate of the wild-type strain. Thus pantothenate supplementation can be
      utilized as a "metabolic switch" for tuning the synthesis rates of molecules
      relying on CoA intermediates and aid the economic scale-up of strains producing
      acyl-CoA derived molecules to manufacturing facilities. 

PMID- 25076382
TI  - Inadvertent Iatrogenic Misuse of Intravenous Diphenhydramine in an Adolescent:
      Implications for Routine Medication Administration.

PMID- 25076381
TI  - Zhankuic acid A as a novel JAK2 inhibitor for the treatment of concanavalin A
      induced hepatitis.
AB  - Fruiting bodies of Taiwanofungus camphoratus have been widely used as an antidote
      for food poisoning and considered to be a precious folk medicine for anti
      inflammation and hepatoprotection. Zhankuic acid A (ZAA) is its major
      pharmacologically active compound. Janus kinase 2 (JAK2), whose activation is
      involved in cytokine signaling, plays critical roles in the development and
      biology of the hematopoietic system. JAK2 has been implicated as a therapeutic
      target in inflammatory diseases. The HotLig modeling approach was used to
      generate the binding model for ZAA with JAK2, showing that ZAA could bind to the
      ATP-binding pocket of JAK2 exclusively via the H-bond. The interaction between
      ZAA and JAK2 was verified by antibody competition assay. Binding of ZAA to JAK2
      reduced antibody recognition of native JAK2. The expressions of phosphorylated
      JAK2 and STATs were analyzed by immuno-blotting. ZAA reduced the phosphorylation
      and downstream signaling of JAK2, and inhibited the interferon (IFN)-gamma/signal
      transducer and activator of transcription (STAT) 1/interferon regulatory factor
      (IRF)-1 pathway. The protective effect of ZAA on liver injury was evaluated in
      mice by Con-A-induced acute hepatitis. Pre-treatment with ZAA also significantly
      ameliorated acute liver injury in mice. Therefore, ZAA can inhibit JAK2
      phosphorylation and protect against liver injury during acute hepatitis in mice.
      In this study, we present data that ZAA exerts anti-inflammatory effects through
      the JAK2 signaling pathway. As such, ZAA may be a potential therapeutic agent for
      the treatment of inflammatory diseases. 

PMID- 25076383
TI  - Behaviour of liquid-fed growing pigs provided with straw in various amounts and
      frequencies.
AB  - Straw possesses many characteristics that make it attractive to pigs and can
      therefore be effective in preventing negative penmate-directed behaviours.
      However, straw is difficult to handle in current vacuum slurry systems under most
      commercial conditions and can therefore only be used in limited amounts. To
      occupy pigs effectively, straw must remain attractive to pigs throughout the
      whole day; hence, have a certain degree of novelty. We investigated the penmate
      directed behaviour of liquid-fed growing pigs in a production herd, assigned to
      five experimental treatments: 1*25, 1*50, 1*100, 2*50 and 4*25 g of chopped
      straw/pig per day, with 20 replicates of each treatment (pen was regarded as
      experimental unit). Behaviour was observed at two different growth stages; ~40
      and 80 kg live weight of the pigs. Activity and exploratory behaviour directed at
      penmates, straw, pen components and the slatted floor were registered
      continuously for 15 min of each hour during day time (0600 to 2200 h) by use of
      video observation of three focal pigs per pen. The pigs were active for about one
      third of the day corresponding to ~5 h/day. Of the active time, an average of 7%
      (35 min) was spent on penmate-directed behaviour. The pigs were more active and
      increased their straw-directed behaviour when provided with 100 g straw/pig per
      day compared with 25 and 50 g (P<0.001). However, penmate-directed behaviour was
      not reduced with an increased amount of straw (P>0.05), and there was no effect
      on pigs' behaviour when straw provision was increased per day (P>0.05). Pigs
      became less active and reduced their straw-directed activities when their weight
      increased from 40 to 80 kg live weight (P<0.001), but the amount of penmate
      directed behaviour was similar (P>0.05). Further, the residual straw results
      indicated that perhaps a more frequent straw provision could help establish a
      more even level of fresh available straw during the day. However, the frequent
      straw provision did not occupy pigs more than one daily allocation did. In
      conclusion, there was no difference in penmate-directed behaviour of the pigs
      when given 25 or 50 g of straw/pig per day compared with 100 g of straw/pig per
      day, nor were there any difference when 100 g of straw/pig per day was provided
      more frequently. 

PMID- 25076384
TI  - Transcontinental movement of Asian genotype chikungunya virus.

PMID- 25076385
TI  - Televised obesity-prevention advertising across US media markets: exposure and
      content, 2010-2011.
AB  - OBJECTIVE: To examine levels of exposure and content characteristics for recent
      televised obesity-prevention campaigns sponsored by state and community health
      departments, federal agencies, non-profit organizations and television stations
      in the USA. DESIGN: Nielsen television ratings for obesity-prevention advertising
      were collected for the top seventy-five US media markets and were used to
      calculate household exposure levels for 2010 and 2011. Governmental
      advertisements were coded for content. SETTING: United States. RESULTS: Average
      household exposure to obesity-prevention campaigns was 2.6 advertisements per
      month. Exposure increased by 31 % between 2010 and 2011, largely driven by
      increases in federal advertisements. In 2011, the federal government accounted
      for 62 % of obesity-prevention exposure, non-profit organizations for 9 %,
      community departments for 8 %, state departments for 3 %, and television station
      sponsored public-service announcements for 17 %. The greatest percentage increase
      between 2010 and 2011 was in community advertising, reflecting efforts funded by
      the Communities Putting Prevention to Work (CPPW) programme. Among thirty-four
      state and community campaigns, the majority advocated both healthy eating and
      physical activity (53 %). Campaigns typically had positive or neutral emotional
      valence (94 %). Obesity or overweight was mentioned in 47 % of campaigns, but
      only 9 % specifically advocated weight loss. CONCLUSIONS: Exposure to televised
      obesity-prevention advertising increased from 2010 to 2011 and was higher than
      previously found in 1999-2003, apart from in 2003 during the federal VERB
      campaign. Nevertheless, exposure remains low relative to advertising for
      unhealthy foods. New federal campaigns have increased exposure to obesity
      prevention advertising nationally, while CPPW grants have increased exposure for
      targeted areas.

PMID- 25076386
TI  - A cohort study of sciatic pain and measures of internal spinal load in
      professional drivers.
AB  - In a prospective cohort study of 537 male professional drivers, the occurrence of
      sciatic pain showed stronger associations with measures of internal lumbar load
      expressed in terms of daily compressive dose, S(ed) (MPa), and risk factor, R
      (non-dimensional), according to ISO/WD 2631-5 (2013), than with measures of daily
      vibration exposure calculated as either 8-h energy-equivalent frequency-weighted
      acceleration (ms(-2) r.m.s.) or vibration dose value (ms(-1.75)) according to the
      EU Directive on mechanical vibration (2002). Herniated lumbar disc, previous
      lumbar trauma and physical work load were also powerful predictors of the
      occurrence of sciatic pain over time. Psychosocial work environment was poorly
      associated with sciatic pain. The boundary values of risk factor (R) for low and
      high probabilities of adverse health effects on the lumbar spine, as proposed by
      international standard ISO/WD 2631-5 (2013), tend to underestimate the health
      risk in professional drivers. PRACTITIONER SUMMARY: In a prospective cohort study
      of professional drivers, measures of internal spinal load were better predictors
      of the occurrence of sciatic pain than the measures of daily vibration exposure
      established by the EU Directive (2002). Herniated lumbar disc, lumbar trauma and
      physical work load were also associated with sciatic pain.

PMID- 25076387
TI  - Prevention of central venous catheter-related infection in the neonatal unit: a
      literature review.
AB  - Central venous catheter infections are the leading cause of healthcare-associated
      bloodstream infections and contribute significantly to mortality and morbidity in
      neonatal intensive care units. Moreover, infection poses significant economic
      consequence which increased hospital costs and increased length of hospital stay.
      Prevention strategies are detailed in guidelines published by the Centers for
      Disease Control and Prevention (CDC) in the United States; nevertheless, recent
      surveys in neonatal units in the United States, and Australia and New Zealand
      demonstrate these are not always followed. This review discusses the numerous
      evidence-based strategies to prevent catheter infections including hand hygiene,
      maximal sterile barriers during insertion, skin disinfection, selection of
      insertion site, dressings, aseptic non-touch technique, disinfection of catheter
      hubs/ports, administration set management, prompt removal of catheter, antibiotic
      locks, systemic antibiotic prophylaxis and chlorhexidine bathing. Furthermore, it
      will describe different strategies that can be implemented into clinical practice
      to reduce infection rates. These include the use of care bundles including
      checklists, education and the use of CVC teams. 

PMID- 25076389
TI  - Fatigue in Air Medical Clinicians Undertaking High-acuity Patient Transports.
AB  - Abstract Background. Fatigue is likely to be a significant issue for air medical
      transport clinicians due to the challenging nature of their work, but there is
      little published evidence for this. Objective. To prospectively assess the levels
      and patterns of fatigue in air medical transport teams and determine whether
      specific mission factors influenced clinician fatigue. Methods. Physicians and
      flight nurses from two intensive care interhospital transport teams routinely
      completed fatigue report forms before and after patient transport missions over a
      4-month period. Data collected included subjective ratings of fatigue (Samn
      Perelli and visual analog scale), mission difficulty and performance.
      Multivariate hierarchical logistic and linear models were used to evaluate the
      influence of various mission characteristics on post-mission fatigue. Results.
      Clinicians returned 403 fully complete fatigue report forms at an estimated
      overall return rate of 73%. Fatigue increased significantly over the course of
      missions, and on 1 of every 12 fatigue reports returned clinicians reported
      severe post-mission fatigue (that is, levels of 6 or 7 on the Samn-Perelli
      scale). Factors that impacted significantly on clinician fatigue were the pre
      mission fatigue level of the clinician, night work, mission duration, and mission
      difficulty. Poorer self-rated performance was significantly associated with
      higher levels of fatigue (r = -0.4, 95% CI -0.5 to -0.3), and for the 6-month
      period leading up to the study clinicians reported a total of 22 occasions on
      which they should have declined a mission due to fatigue. Conclusions. These
      results suggest that clinicians undertaking interhospital transports of even
      moderate duration experience high levels of fatigue on a relatively frequent
      basis. In the unique and challenging environment of air medical transport, prior
      fatigue, long or difficult missions, and the disadvantageous effect of night work
      on normal circadian rhythms are a combination where there are minimal safety
      margins for clinicians' performance capacity. Fatigue prevention or fatigue
      resistance measures could positively affect air medical clinicians in this
      context.

PMID- 25076388
TI  - Duodenal bulb histological analysis should be standard of care when evaluating
      celiac disease in children.
AB  - We confirmed the added value provided by sampling D1 in the diagnosis of CD in
      comparison to the diagnosis yield when only the more distal duodenum (D2, D3,
      and/or D4) was sampled. The severity of CD, as assessed by the Marsh-Oberhuber
      classification, did not increase distally; on the contrary, in 39/60 (65%) of the
      cohort, the features of CD were either more severe or only present in D1.

PMID- 25076392
TI  - Photopatterned antibodies for selective cell attachment.
AB  - We present a phototriggerable system that allows for the spatiotemporal
      controlled attachment of selected cell types to a biomaterial using immobilized
      antibodies that specifically target individual cell phenotypes. o-Nitrobenzyl
      caged biotin was used to functionalize chitosan membranes and mediate site
      specific coupling of streptavidin and biotinylated antibodies after light
      activation. The ability of this system to capture and immobilize specific cells
      on a surface was tested using endothelial-specific biotinylated antibodies and
      nonspecific ones as controls. Homogeneous patterned monolayers of human umbilical
      vein endothelial cells were obtained on CD31-functionalized surfaces. This is a
      simple and generic approach that is applicable to other ligands, materials, and
      cell types and shows the flexibility of caged ligands to trigger and control the
      interaction between cells and biomaterials. 

PMID- 25076393
TI  - Kinetics and intermediates of the reaction of fully reduced Escherichia coli bo3
      ubiquinol oxidase with O2.
AB  - Cytochrome bo3 ubiquinol oxidase from Escherichia coli catalyzes the reduction of
      O2 to water by ubiquinol. The reaction mechanism and the role of ubiquinol
      continue to be a subject of discussion. In this study, we report a detailed
      kinetic scheme of the reaction of cytochrome bo3 with O2 with steps specific to
      ubiquinol. The reaction was investigated using the CO flow-flash method, and time
      resolved optical absorption difference spectra were collected from 1 MUs to 20 ms
      after photolysis. Singular value decomposition-based global exponential fitting
      resolved five apparent lifetimes, 22 MUs, 30 MUs, 42 MUs, 470 MUs, and 2.0 ms.
      The reaction mechanism was derived by an algebraic kinetic analysis method using
      frequency-shifted spectra of known bovine states to identify the bo3
      intermediates. It shows 42 MUs O2 binding (3.8 * 10(7) M(-1) s(-1)), producing
      compound A, followed by faster (22 MUs) heme b oxidation, yielding a mixture of
      PR and F, and rapid heme b rereduction by ubiquinol (30 MUs), producing the F
      intermediate and semiquinone. In the 470 MUs step, the o3 F state is converted
      into the o3(3+) oxidized state, presumably by semiquinone/ubiquinol, without the
      concomitant oxidation of heme b. The final 2 ms step shows heme b reoxidation and
      the partial rereduction of the binuclear center and, following O2 binding, the
      formation of a mixture of P and F during a second turnover cycle. The results
      show that ubiquinol/semiquinone plays a complex role in the mechanism of O2
      reduction by bo3, displaying kinetic steps that have no analogy in the CuA
      containing heme-copper oxidases.

PMID- 25076395
TI  - Clinical inertia and champions for change.

PMID- 25076394
TI  - Urinary isothiocyanates level and liver cancer risk: a nested case-control study
      in Shanghai, China.
AB  - Experimental studies have provided evidence that isothiocyanates (ITCs) from
      cruciferous vegetables may modulate carcinogen metabolism and facilitate
      carcinogen detoxification and reduce cancer risk. However, no epidemiological
      studies on liver cancer were reported. This study investigates the association
      between urinary ITCs levels and liver cancer risk among men and women in
      Shanghai, China. A nested case-control study of 217 incident cases of liver
      cancer and 427 matched controls identified from the Shanghai Women's Health Study
      and Shanghai Men's Health Study was conducted. Conditional logistic regression
      was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs)
      summarizing the association between urinary ITCs levels and liver cancer risk.
      Compared to those with undetectable ITCs, nonsignificantly inverse association
      was observed among detectable (OR = 0.80; 95% CI = 0.51-1.26), below-median (OR =
      0.76; 95% CI = 0.47-1.24), and above-median concentration (OR = 0.86; 95% CI =
      0.52-1.41) with liver cancer risk. Similar patterns were observed when urinary
      ITCs levels were categorized into tertiles or quartiles. Although our study
      firstly focused on the association between urinary ITCs exposure and liver cancer
      risk, we did not find significant results. Future multicenter prospective,
      different population studies are warranted to validate our findings. 

PMID- 25076396
TI  - Gait speed in the emergency department: improving assessment among older adults.
AB  - The research to practice column is intended to improve the research critique
      skills of the advanced practice registered nurse (APRN) and to assist with the
      translation of research into practice. This column critiques the findings from a
      meta-analysis, "Gait speed and survival in older adults," by S. Studenski et al.
      (2011). The study was designed to assess the use of gait speed as a physical
      performance measure that is associated with survival. The findings are reviewed
      in the context of increasing emergency department (ED) visits among older adults
      and their unique assessment needs, with implications for APRN best care
      practices. The implementation of gait speed as a screening tool for identifying
      adults 65 years of age and older in the ED who may be at risk for adverse events
      and functional decline will also be discussed.

PMID- 25076397
TI  - Recurrent intussusception in a 4-year-old male.
AB  - Acute abdominal pain in children is a common complaint in the emergency
      department. The etiology of abdominal pain in children can range from benign to
      life-threatening, and the clinical diagnosis and treatment must be timely and
      accurate. This case describes a 4-year-old boy with intussusception, a serious
      disorder with the potential for life-threatening consequences. Children with
      intussusception may be relatively asymptomatic or present as an acutely ill child
      with severe abdominal pain, lethargy, dehydration, and shock. Diagnosing
      intussusception may be very challenging. The purpose of this article is to
      discuss the pathophysiology, diagnostic workup, management, and follow-up of
      abdominal pain in a child. 

PMID- 25076398
TI  - Being prepared: bioterrorism and mass prophylaxis: part I.
AB  - Bioterrorism presents a real and omnipresent risk to public health throughout the
      world. More than 30 biological agents have been identified as possessing the
      potential to be deployed in a bioterrorist attack. Those that have been
      determined to be of the greatest concern and possess the greatest potential of
      use in this arena are known as the Category A agents: Bacillus anthracis
      (anthrax); Variola major (smallpox); Yersinia pestis (plague); Francisella
      tularensis (tularemia); viral hemorrhagic fevers; and Clostridium botulinum toxin
      (botulism toxin). Although the Centers for Disease Control and Prevention
      utilizes surveillance systems to identify illnesses, the weight of diagnosing,
      effectively treating, and notifying the appropriate public health officials lies
      squarely on the shoulders of emergency care personnel. Part I of this two-part
      review will focus on the clinical presentation and treatment of anthrax, plague,
      and tularemia. The subsequent Part II of this review will discuss smallpox, viral
      hemorrhagic fevers, botulism toxin, and the provision of mass prophylaxis. 

PMID- 25076400
TI  - A purple rash: a case study of Henoch-Schonlein purpura.
AB  - Rashes are one of the most common presenting symptoms in the emergency department
      setting; they may be a primary diagnosis or a symptom of systemic disease.
      Accurate diagnosis of a rash may be challenging and requires clinical acumen,
      systematic history and physical examination, and judicious use of diagnostic
      testing. This case study reviews Henoch-Schonlein purpura (HSP) or IgA
      vasculitis, a common vasculitis of childhood. Although typically a self-limited
      disease, HSP may cause serious complications in a small subset of patients and
      requires monitoring. In addition, there are several differential diagnoses that
      may mimic HSP that are more serious. This article reviews the case of a 6-year
      old boy who presented to a community emergency department and had a nontypical
      clinical course. 

PMID- 25076401
TI  - Psychometric testing of the Agitation Severity Scale for acute presentation
      behavioral management patients in the emergency department.
AB  - Agitation is a vexing problem frequently observed in emergency department acute
      psychiatric patients, yet no instruments to measure agitation in this setting and
      population were found upon review of the literature. Previously developed
      agitation rating scales are limited by the length of observation they require,
      their need for participation by the patient, complexity in scoring, and a lack of
      validity in this setting and population. The purpose of this study was to
      psychometrically evaluate and refine an observation-based agitation scale for use
      with emergency department acute psychiatric patients. Using a methodological
      design, the 21-item Agitation Severity Scale was utilized to assess 270 adult
      psychiatric patients in the emergency setting in a prospective, observational
      fashion. Reliability analysis, item analysis, exploratory factor analysis, and
      validity assessments were completed. The relationship between Agitation Severity
      Scale scores and scores on the previously established Overt Agitation Severity
      Scale was evaluated. The instrument was reduced to 17 items representing four
      factors (Aggressive Behaviors, Interpersonal Behaviors, Involuntary Motor
      Behaviors, and Physical Stance) that accounted for nearly 70% of observed
      variance, Cronbach's alpha = 0.91. Evidence of internal consistency reliability,
      equivalence reliability, construct validity, and convergent validity was
      established. Through this study, the 17-item Agitation Severity Scale
      demonstrated acceptable levels of reliability and validity when used with acute
      psychiatric patients in the emergency setting. This instrument holds promise as a
      method of enhancing clinical communication about agitation, evaluating the
      efficacy of interventions aimed at decreasing agitation, and as a research tool. 

PMID- 25076402
TI  - Ultrasound measurement of inferior vena cava diameters by emergency department
      nurses.
AB  - Sonographic measurement of the inferior vena cava (IVC) diameter is a potentially
      important noninvasive estimate of fluid status. We researched whether nurses
      without prior ultrasonography experience could accurately obtain vena cava
      diameter measurements on models and subjects in comparison with those obtained by
      an expert sonographer. The design was a prospective educational study using a pre
      and posttest of knowledge and a comparison of imaging performance between a
      subject and an expert sonographer. The setting was an urban teaching medical
      center with emergency nurses and a convenience sample of volunteer patients
      selected from the emergency department (ED). Nurses completed a written survey
      and a pretest to document prior training and experience in ultrasonography and
      assess baseline knowledge. A structured training program (3.5 hr in length) was
      provided over three sessions. Training consisted of didactic presentations,
      practice on phantoms (manikin models designed to provide the sonographic image of
      the human body when scanned by a trainee) and classmates, and one volunteer
      patient in the ED. Each nurse then measured IVC diameters on three different
      volunteer patients in transverse and longitudinal orientations using frozen
      images. An expert sonographer, blinded to subject results, performed the same
      examination. Correlations were determined, and a posttraining written examination
      was completed and results compared with the pretest using a pair-wise t test.
      Fourteen nurses, with a mean of 8 years' nursing experience (range = 2-18 years),
      participated. Nurse-expert R value correlation for the longitudinal orientation
      was 0.68 (95% confidence interval [CI] [0.35, 0.76]) and 0.59 (95% CI [0.47,
      0.81]) for the transverse orientation. Posttest scores improved 8.2 percentage
      points (95% CI [4.0, 12.4]) from 83.3% to 91.5%. Following a brief training
      course, nurses with no prior sonography experience show moderately good
      correlation measuring the IVC diameter as compared with expert measurements, with
      better performance demonstrated in the longitudinal orientation. 

PMID- 25076403
TI  - Profiling emergency nurse practitioner service: an interpretive study.
AB  - The aim of this study was to investigate the practice profile of emergency nurse
      practitioners across Australia. Nurse practitioners have been providing health
      service in the emergency setting internationally for more than 30 years, and
      evidence supports the value of this role in terms of patient satisfaction,
      effectiveness in improving service indicators, and acceptability of the role. The
      introduction of this service model has been instrumental in reducing waiting
      times for low-acuity patients and impacting positively on emergency department
      service delivery. Recent rapid uptake of this role internationally has outpaced
      development of the service model to inform education and ongoing service
      development. This was a national study that used interpretive research methods to
      identify the practice profile of emergency nurse practitioners. Data were
      collected from December 2012 to February 2013 through in-depth interviews. An
      inductive approach was used in data analysis to identify conceptual themes and
      develop an analysis framework. The study participants worked in a range of
      service models and managed patient presentations across all levels of acuity and
      complexity. The findings show that although there is no single definable model of
      the emergency nurse practitioner role in Australia, there are practice features
      that are common across all service models; these have been conceptualized as
      "modes of practice." This study has produced new knowledge about the practice
      profile of emergency nurse practitioners. The findings will inform development of
      practice standards for education and continuing professional development for
      emergency nurse practitioners and facilitate standardized operational definitions
      for ongoing research into this growing service model. 

PMID- 25076404
TI  - Stabilization, isomerization and rearrangement of enyne [4 + 4]-cycloadducts.
AB  - Reactive 1,2,5-cyclooctatrienes, formed by photocycloaddition of 2-pyridones with
      enynes, are stabilized by steric shielding, slowing or preventing an otherwise
      facile [2 + 2]-dimerization reaction. Diisopropylsilyl ether-tethered reactants
      paired with an alkene substituent (R) produce allenes that are stable (R = TMS)
      or that isomerize to 1,3-dienes by hydrogen migration (R = alkyl). Under acidic
      conditions, hydrolysis of the photoproduct's silyl ether can lead to a [3,3]
      sigmatropic rearrangement. 

PMID- 25076405
TI  - All-inorganic networks and tetramer based on tin(II)-containing polyoxometalates:
      tuning structural and spectral properties with lone-pairs.
AB  - Two MOF-like but all-inorganic polyoxometalate-based networks,
      [Na7X2W18Sn9Cl5O68.(H2O)m]n (1, X = Si, m = 35; 2, X = Ge, m = 41), and the
      molecular tetramer Na6[{Na(MU-OH2)(OH2)2}6{Sn6(B-SbW9O33)2}2].50H2O (3) have been
      prepared and characterized by X-ray diffraction and spectroscopic methods. All
      three compounds exhibit unique structural features, and networks 1 and 2
      incorporate the highest nuclearity of Sn(II)-containing POMs to date. Tetramer 3
      comprises bridging Sn(II) ions with [B-SbW9O33](9-) units and exhibits two highly
      unusual features, a long-range Sb...Sb interaction and an intramolecular charge
      transfer transition involving donation of the lone-pair electron density on both
      Sb(III) and Sn(II) to the POM. The electronic structure and excited-state
      dynamics have been studied by transient spectroscopy, spectroelectrochemistry,
      DFT calculations, and resonance Raman spectroscopy. The synergistic effect of two
      types of stereoactive lone-pairs on Sb(III) and Sn(II) is critical for the charge
      transfer absorption feature in the visible. 

PMID- 25076406
TI  - Quartic force field rovibrational analysis of protonated acetylene, C2H3(+), and
      its isotopologues.
AB  - Protonated acetylene, C2H3(+), is among the simplest carbocations. Comprehensive
      experimental or highly accurate computational spectroscopic data is lacking for
      this system due to its inherent complexities. Utilizing state-of-the-art quartic
      force fields (QFFs), the spectroscopic constants and fundamental vibrational
      frequencies are provided in this work for the nonclassical, bridged, cyclic
      global minimum. The rotational constants match experiment to better than 0.1%,
      and the computed nu2 antisymmetric HCCH stretch is less than 3.0 cm(-1) different
      from experiment. Hence, the rovibrational spectroscopic data provided herein for
      c-C2H3(+) and its deuterated isotopologues enrich the chemical understanding of
      this system. Unfortunately, the same rovibrational spectroscopic data is not as
      trustworthy for the classical, linear form of protonated acetylene due to the
      shallow well in which it resides on the potential energy surface. However,
      spectroscopic data are provided for this isomer in the Supporting Information to
      enhance future studies.

PMID- 25076407
TI  - Movement patterns of juvenile whale sharks tagged at an aggregation site in the
      Red Sea.
AB  - Conservation efforts aimed at the whale shark, Rhincodon typus, remain limited by
      a lack of basic information on most aspects of its ecology, including global
      population structure, population sizes and movement patterns. Here we report on
      the movements of 47 Red Sea whale sharks fitted with three types of satellite
      transmitting tags from 2009-2011. Most of these sharks were tagged at a single
      aggregation site near Al-Lith, on the central coast of the Saudi Arabian Red Sea.
      Individuals encountered at this site were all juveniles based on size estimates
      ranging from 2.5-7 m total length with a sex ratio of approximately 1?1. All
      other known aggregation sites for juvenile whale sharks are dominated by males.
      Results from tagging efforts showed that most individuals remained in the
      southern Red Sea and that some sharks returned to the same location in subsequent
      years. Diving data were recorded by 37 tags, revealing frequent deep dives to at
      least 500 m and as deep as 1360 m. The unique temperature-depth profiles of the
      Red Sea confirmed that several whale sharks moved out of the Red Sea while
      tagged. The wide-ranging horizontal movements of these individuals highlight the
      need for multinational, cooperative efforts to conserve R. typus populations in
      the Red Sea and Indian Ocean. 

PMID- 25076408
TI  - Extracellular HCV-core protein induces an immature regulatory phenotype in NK
      cells: implications for outcome of acute infection.
AB  - BACKGROUND: Hepatitis C viral (HCV) proteins, including core, demonstrate immuno
      modulatory properties; however, the effect of extracellular core on natural
      killer (NK) cells has not previously been investigated. AIMS: To characterise NKs
      in acute HCV infection over time, and, to examine the effect of exogenous HCV
      core protein on NK cell phenotype and function. METHODS: Acute HCV patients (n =
      22), including 10 subjects who spontaneously recovered, were prospectively
      studied. Flow-cytometry was used to measure natural cytotoxicity and to phenotype
      NKs directly ex vivo and after culture with HCV-core protein. Microarray analysis
      was used to identify pathways involved in the NK cell response to exogenous HCV
      core. RESULTS: Direct ex vivo analysis demonstrated an increased frequency of
      immature/regulatory CD56bright NKs early in acute HCV infection per se which
      normalized with viral clearance. Natural cytotoxicity was reduced and did not
      recover after viral clearance. There was a statistically significant correlation
      between the frequency of CD56bright NKs and circulating serum levels of HCV core
      protein. In vitro culture of purified CD56bright NK cells with HCV-core protein
      in the presence of IL-15 maintained a significant proportion of NKs in the
      CD56bright state. The in vitro effect of core closely correlates with NK
      characteristics measured directly ex vivo in acute HCV infection. Pathway
      analysis suggests that HCV-core protein attenuates NK interferon type I
      responses. CONCLUSIONS: Our data suggest that HCV-core protein alters NK cell
      maturation and may influence the outcome of acute infection.

PMID- 25076409
TI  - Aspiration-related deaths in 57 consecutive patients: autopsy study.
AB  - BACKGROUND: Aspiration can cause a diverse spectrum of pulmonary disorders some
      of which can lead to death but can be difficult to diagnose. PATIENTS AND
      METHODS: The medical records and autopsy findings of 57 consecutive patients in
      whom aspiration was the immediate cause of death at Mayo Clinic (Rochester, MN,
      USA) over a 9-yr period, from January 1 2004 to December 31 2012 were analyzed.
      RESULTS: The median age at death was 72 years (range, 13-95 years) and included
      39 (68%) males. The most common symptom before death was dyspnea (63%) and chest
      radiography revealed bilateral infiltrates in the majority (81%). Most common
      precipitating factors for aspiration were depressed consciousness (46%) and
      dysphagia (44%). Aspiration-related syndromes leading to death were aspiration
      pneumonia in 26 (46%), aspiration pneumonitis in 25 (44%), and large airway
      obstruction in 6 patients (11%). Aspiration was clinically unsuspected in 19
      (33%) patients. Antimicrobial therapy had been empirically administered to most
      patients (90%) with aspiration pneumonia and aspiration pneumonitis. CONCLUSION:
      We conclude aspiration-related deaths occur most commonly in the elderly with
      identifiable risks and presenting bilateral pulmonary infiltrates. One-third of
      these aspiration-related pulmonary syndromes were clinically unsuspected at the
      time of death.

PMID- 25076410
TI  - Discovering social events through online attention.
AB  - Twitter is a major social media platform in which users send and read messages
      ("tweets") of up to 140 characters. In recent years this communication medium has
      been used by those affected by crises to organize demonstrations or find relief.
      Because traffic on this media platform is extremely heavy, with hundreds of
      millions of tweets sent every day, it is difficult to differentiate between times
      of turmoil and times of typical discussion. In this work we present a new
      approach to addressing this problem. We first assess several possible
      "thermostats" of activity on social media for their effectiveness in finding
      important time periods. We compare methods commonly found in the literature with
      a method from economics. By combining methods from computational social science
      with methods from economics, we introduce an approach that can effectively locate
      crisis events in the mountains of data generated on Twitter. We demonstrate the
      strength of this method by using it to locate the social events relating to the
      Occupy Wall Street movement protests at the end of 2011. 

PMID- 25076411
TI  - Polymorphic copper iodide clusters: insights into the mechanochromic luminescence
      properties.
AB  - An in-depth study of mechanochromic and thermochromic luminescent copper iodide
      clusters exhibiting structural polymorphism is reported and gives new insights
      into the origin of the mechanochromic luminescence properties. The two different
      crystalline polymorphs exhibit distinct luminescence properties with one being
      green emissive and the other one being yellow emissive. Upon mechanical grinding,
      only one of the polymorphs exhibits great modification of its emission from green
      to yellow. Interestingly, the photophysical properties of the resulting partially
      amorphous crushed compound are closed to those of the other yellow polymorph.
      Comparative structural and optical analyses of the different phases including a
      solution of clusters permit us to establish a correlation between the Cu-Cu bond
      distances and the luminescence properties. In addition, the local structure of
      the [Cu4I4P4] cluster cores has been probed by (31)P and (65)Cu solid-state NMR
      analysis, which readily indicates that the grinding process modifies the
      phosphorus and copper atoms environments. The mechanochromic phenomenon is thus
      explained by the disruption of the crystal packing within intermolecular
      interactions inducing shortening of the Cu-Cu bond distances in the [Cu4I4]
      cluster core and eventually modification of the emissive state. These results
      definitely establish the role of cuprophilic interactions in the mechanochromism
      of copper iodide clusters. More generally, this study constitutes a step further
      into the understanding of the mechanism involved in the mechanochromic
      luminescent properties of metal-based compounds. 

PMID- 25076412
TI  - Generation of dihydrogen molecule and hydrosilylation of carbon dioxide catalyzed
      by zinc hydride complex: theoretical understanding and prediction.
AB  - Generation of H2 from methanol/water and hydrosilylation of CO2 catalyzed by
      [tris(2-pyridylthio)methyl]zinc hydride [kappa(3)-Tptm]ZnH 1 were investigated
      with DFT and MP2 methods. The hydrosilylation of CO2 occurs via the CO2 insertion
      into the Zn-H bond of 1 followed by the metathesis of a Zn-(eta(1)-OCOH) bond
      with hydrosilane to yield silyl formate and regenerate 1. The CO2 insertion
      easily occurs, but the metathesis is difficult because of the formation of a very
      stable Zn-(eta(2)-O2CH) species before the metathesis. The DeltaG degrees (?)
      value of the metathesis with triethoxysilane is much smaller than that with
      phenylsilane because electronegative methoxy groups stabilize the transition
      state bearing hypervalent Si center, which is consistent with the experimental
      result that triethoxysilane is used in the hydrosilylation of CO2. It is
      theoretically predicted here that hydrosilane with two electronegative OEt groups
      or one to three F groups can be applied to this reaction. In the generation of H2
      from methanol/water by 1, the first step is the metathesis of 1 with the O-H bond
      of methanol/water to produce [kappa(3)-Tptm]Zn(OMe)/[k(3)-Tptm]Zn(OH) and
      dihydrogen molecule. The next step is the metathesis of the Zn-OMe/Zn-OH bond
      with hydrosilane to yield silyl ether and regenerate 1. The first metathesis is
      rate-determining but the second one occurs with very small activation energy,
      indicating that various hydrosilanes can be applied to this reaction.

PMID- 25076413
TI  - Theoretical study of the formation of mercury (Hg2+) complexes in solution using
      an explicit solvation shell in implicit solvent calculations.
AB  - The structures and harmonic vibrational frequencies of water clusters (H2O)n, n =
      1-10, have been computed using the M06-L/, B3LYP/, and CAM-BLYP/cc-pVTZ levels of
      theories. On the basis of the literature and our results, we use three hexamer
      structures of the water molecules to calculate an estimated "experimental"
      average solvation free energy of [Hg(H2O)6](2+). Aqueous formation constants (log
      K) for Hg(2+) complexes, [Hg(L)m(H2O)n](2-mq), L = Cl(-), HO(-), HS(-), and S(2
      ), are calculated using a combination of experimental (solvation free energies of
      ligands and Hg(2+)) and calculated gas- and liquid-phase free energies. A
      combined approach has been used that involves attaching n explicit water
      molecules to the Hg(2+) complexes such that the first coordination sphere is
      complete, then surrounding the resulting (Hg(2+)-Lm)-(OH2)n cluster by a
      dielectric continuum, and using suitable thermodynamic cycles. This procedure
      significantly improves the agreement between the calculated log K values and
      experiment. Thus, for some neutral and anionic Hg(II) complexes, particularly
      Hg(II) metal ion surrounded with homo- or heteroatoms, augmenting implicit
      solvent calculations with sufficient explicit water molecules to complete the
      first coordination sphere is required-and adequate-to account for strong short
      range hydrogen bonding interactions between the anion and the solvent. Calculated
      values for formation constants of Hg(2+) complexes with S(2-) and SH(-) are
      proposed. Experimental measurements of these log K values have been lacking or
      controversial. 

PMID- 25076415
TI  - Using participatory risk mapping (PRM) to identify and understand people's
      perceptions of crop loss to animals in Uganda.
AB  - Considering how people perceive risks to their livelihoods from local wildlife is
      central to (i) understanding the impact of crop damage by animals on local people
      and (ii) recognising how this influences their interactions with, and attitudes
      towards, wildlife. Participatory risk mapping (PRM) is a simple, analytical tool
      that can be used to identify and classify risk within communities. Here we use it
      to explore local people's perceptions of crop damage by wildlife and the animal
      species involved. Interviews (n = 93, n = 76) and seven focus groups were
      conducted in four villages around Budongo Forest Reserve, Uganda during 2004 and
      2005. Farms (N = 129) were simultaneously monitored for crop loss. Farmers
      identified damage by wildlife as the most significant risk to their crops; risk
      maps highlighted its anomalous status compared to other anticipated challenges to
      agricultural production. PRM was further used to explore farmers' perceptions of
      animal species causing crop damage and the results of this analysis compared with
      measured crop losses. Baboons (Papio anubis) were considered the most problematic
      species locally but measurements of loss indicate this perceived severity was
      disproportionately high. In contrast goats (Capra hircus) were considered only a
      moderate risk, yet risk of damage by this species was significant. Surprisingly,
      for wild pigs (Potamochoerus sp), perceptions of severity were not as high as
      damage incurred might have predicted, although perceived incidence was greater
      than recorded frequency of damage events. PRM can assist researchers and
      practitioners to identify and explore perceptions of the risk of crop damage by
      wildlife. As this study highlights, simply quantifying crop loss does not
      determine issues that are important to local people nor the complex relationships
      between perceived risk factors. Furthermore, as PRM is easily transferable it may
      contribute to the identification and development of standardised approaches of
      mitigation across sites of negative human-wildlife interaction.

PMID- 25076417
TI  - Engineered micro- and nanoscale diamonds as mobile probes for high-resolution
      sensing in fluid.
AB  - The nitrogen-vacancy (NV) center in diamond is an attractive platform for quantum
      information and sensing applications because of its room temperature operation
      and optical addressability. A major research effort focuses on improving the
      quantum coherence of this defect in engineered micro- and nanoscale diamond
      particles (DPs), which could prove useful for high-resolution sensing in fluidic
      environments. In this work we fabricate cylindrical diamonds particles with
      finely tuned and highly reproducible sizes (diameter and height ranging from 100
      to 700 and 500 nm to 2 MUm, respectively) using high-purity, single-crystal
      diamond membranes with shallow-doped NV centers. We show that the spin coherence
      time of the NV centers in these particles exceeds 700 MUs, opening the
      possibility for the creation of ultrahigh sensitivity micro- and nanoscale
      sensors. Moreover, these particles can be efficiently transferred into a water
      suspension and delivered to the region to probe. In particular, we introduce a DP
      suspension inside a microfluidic circuit and control position and orientation of
      the particles using an optical trapping apparatus. We demonstrate a DC magnetic
      sensitivity of 9 MUT/?Hz in fluid as well as long-term trapping stability (>30
      h), which paves the way toward the use of high-sensitivity pulse techniques on
      contactless probes manipulated within biological settings. 

PMID- 25076416
TI  - Age and date for early arrival of the Acheulian in Europe (Barranc de la Boella,
      la Canonja, Spain).
AB  - The first arrivals of hominin populations into Eurasia during the Early
      Pleistocene are currently considered to have occurred as short and poorly dated
      biological dispersions. Questions as to the tempo and mode of these early
      prehistoric settlements have given rise to debates concerning the taxonomic
      significance of the lithic assemblages, as trace fossils, and the geographical
      distribution of the technological traditions found in the Lower Palaeolithic
      record. Here, we report on the Barranc de la Boella site which has yielded a
      lithic assemblage dating to ~1 million years ago that includes large cutting
      tools (LCT). We argue that distinct technological traditions coexisted in the
      Iberian archaeological repertoires of the late Early Pleistocene age in a similar
      way to the earliest sub-Saharan African artefact assemblages. These differences
      between stone tool assemblages may be attributed to the different chronologies of
      hominin dispersal events. The archaeological record of Barranc de la Boella
      completes the geographical distribution of LCT assemblages across southern
      Eurasia during the EMPT (Early-Middle Pleistocene Transition, circa 942 to 641
      kyr). Up to now, chronology of the earliest European LCT assemblages is based on
      the abundant Palaeolithic record found in terrace river sequences which have been
      dated to the end of the EMPT and later. However, the findings at Barranc de la
      Boella suggest that early LCT lithic assemblages appeared in the SW of Europe
      during earlier hominin dispersal episodes before the definitive colonization of
      temperate Eurasia took place. 

PMID- 25076418
TI  - Protein trafficking in Plasmodium falciparum-infected red cells and impact of the
      expansion of exported protein families.
AB  - SUMMARY Erythrocytes are extensively remodelled by the malaria parasite following
      invasion of the cell. Plasmodium falciparum encodes numerous virulence-associated
      and host-cell remodelling proteins that are trafficked to the cytoplasm, the cell
      membrane and the surface of the infected erythrocyte. The export of soluble
      proteins relies on a sequence directing entry into the secretory pathways in
      addition to an export signal. The export signal consisting of five amino acids is
      termed the Plasmodium export element (PEXEL) or the vacuole transport signal
      (VTS). Genome mining studies have revealed that PEXEL/VTS carrying protein
      families have expanded dramatically in P. falciparum compared with other malaria
      parasite species, possibly due to lineage-specific expansion linked to the unique
      requirements of P. falciparum for host-cell remodelling. The functional
      characterization of such genes and gene families may reveal potential drug
      targets that could inhibit protein trafficking in infected erythrocytes. This
      review highlights some of the recent advances and key knowledge gaps in protein
      trafficking pathways in P. falciparum-infected red cells and speculates on the
      impact of exported gene families in the trafficking pathway.

PMID- 25076419
TI  - Exenatide treatment exerts anxiolytic- and antidepressant-like effects and
      reverses neuropathy in a mouse model of type-2 diabetes.
AB  - BACKGROUND: Comorbid neurobehavioral disturbances and type-2 diabetes mellitus
      (T2DM) warrant immediate research attention. Exenatide, which is a potent and
      selective agonist for the glucagon-like peptide-1 (GLP-1), is used in the
      treatment of T2DM. Exenatide displays a multitude of effects in the central
      nervous system. The aim of this study was to investigate the anxiolytic- and
      antidepressant-like effects and analgesic effects of exenatide in a type-2
      diabetic mouse model. MATERIAL/METHODS: Modified elevated plus-maze test for
      anxiolytic-like, forced swimming test for depression-like behavior and hotplate
      test for neuropathy were used as behavioral tasks. Behavioral parameters were
      investigated in a streptozocin--(100 mg/kg, i.p.) and nicotinamide--(240 mg/kg,
      i.p.) induced type-2 diabetic mouse model. Exenatide (0.1 ug/kg, s.c., twice
      daily) was administered for 2 weeks. Vehicle (control), diabetic, and exenatide
      treated diabetic mice were tested. RESULTS: Our results confirm that exenatide
      exerts anxiolytic- and antidepressant-like effects and might be effective in
      diabetic neuropathy in a diabetic mouse model. CONCLUSIONS: Exenatide may be a
      good candidate as a treatment option for depression, anxiety, and neuropathy in
      patients with type-2 diabetes.

PMID- 25076421
TI  - A rapid improvement in obsessive-compulsive disorder with milnacipran in a
      patient with schizophrenia.

PMID- 25076420
TI  - The relationship between renal function and plasma concentration of the cachectic
      factor zinc-alpha2-glycoprotein (ZAG) in adult patients with chronic kidney
      disease.
AB  - Zinc-alpha2-glycoprotein (ZAG), a potent cachectic factor, is increased in
      patients undergoing maintenance dialysis. However, there is no data for patients
      before initiation of renal replacement therapy. The purpose of the present study
      was to assess the relationship between plasma ZAG concentration and renal
      function in patients with a large range of glomerular filtration rate (GFR).
      Plasma ZAG concentration and its relationship to GFR were investigated in 71
      patients with a chronic kidney disease (CKD) stage 1 to 5, 17 chronic
      hemodialysis (HD), 8 peritoneal dialysis (PD) and 18 non-CKD patients. Plasma ZAG
      concentration was 2.3-fold higher in CKD stage 5 patients and 3-fold higher in HD
      and PD patients compared to non-CKD controls (P<0.01). The hemodialysis session
      further increased plasma ZAG concentration (+39%, P<0.01). An inverse
      relationship was found between ZAG levels and plasma protein (rs = -0.284;
      P<0.01), albumin (rs = -0.282, P<0.05), hemoglobin (rs = -0.267, P<0.05) and HDL
      cholesterol (rs = -0.264, P<0.05) and a positive correlation were seen with
      plasma urea (rs = 0.283; P<0.01). In multiple regression analyses, plasma urea
      and HDL-cholesterol were the only variables associated with plasma ZAG (r2 =
      0.406, P<0.001). In CKD-5 patients, plasma accumulation of ZAG was not correlated
      with protein energy wasting. Further prospective studies are however needed to
      better elucidate the potential role of ZAG in end-stage renal disease.

PMID- 25076422
TI  - Plasma clusterin (ApoJ) levels are associated with adiposity and systemic
      inflammation.
AB  - Obesity and insulin resistance are hallmarks of the metabolic syndrome, which is
      associated with low-grade chronic inflammation. Clusterin/apolipoprotein J is an
      abundant plasma chaperone protein that has recently been suggested as a potential
      biomarker that reflects the inflammatory process in Alzheimer's disease. In the
      present study, we investigated anthropometric and clinical factors affecting the
      plasma levels of clusterin in healthy Korean subjects. We measured fasting plasma
      clusterin levels in healthy Korean adults (111 men and 93 women) using ELISA kit.
      We analyzed the relationship between plasma clusterin concentrations and
      anthropometric and clinical parameters. Fasting plasma clusterin concentrations
      were higher in overweight and obese subjects than in lean subjects. Correlation
      analysis revealed that the plasma clusterin levels were positively associated
      with indices of obesity such as body mass index (BMI), waist circumference and
      waist-hip ratio and markers of systemic inflammation such as high sensitivity C
      reactive protein (hsCRP), uric acid, ferritin and retinol binding protein-4.
      Multiple linear regression analysis showed that sex, BMI and hsCRP were
      independent determinants of plasma clusterin levels. Furthermore, plasma
      clusterin levels showed an upward trend with increasing numbers of metabolic
      syndrome components. These findings suggest that fasting plasma clusterin levels
      correlate with the parameters of adiposity and systemic inflammation in healthy
      adults. Therefore, the circulating clusterin level may be a surrogate marker for
      obesity-associated systemic inflammation. 

PMID- 25076424
TI  - Ultrastructural characterization of in vivo-produced ovine morulae and
      blastocysts.
AB  - The ultrastructure of in vivo-produced ovine embryos, at the morula, early
      blastocyst and late blastocyst stages, was evaluated using transmission electron
      microscopy. Embryonic cells were characterized by the presence of intact
      intercellular junctions, numerous mitochondria, smooth endoplasmic reticulum
      cisternae and light vesicles. Polyribosomes, rough endoplasmic reticulum
      cisternae, secondary lysosomes, Golgi complexes and lipid droplets were also
      observed in the cytoplasm. The nucleus was well defined and organized, with an
      intact envelope rich in nuclear pore complexes, and one or more reticular
      nucleoli. Microvilli were present in external blastomeres of morulae and became
      more abundant in trophectoderm cells of early and late blastocysts. Light
      vesicles seemed to be associated with small cisternae of Golgi and endoplasmic
      reticulum origin. These cisternae fused and created light vesicles with engulfed
      heterogeneous cytosolic structures, small cisternae and vesicles. Their labile
      membrane enabled them to rapidly coalesce into medium-sized vesicles that began
      to engulf mitochondria and lipid droplets, forming giant vacuoles mostly filled
      with fat. Incomplete matured secretory vesicles were observed to exocytose into
      the perivitelline space of morulae, whereas fully matured secretory vesicles
      appeared only in trophectoderm cells, being exocytosed into the blastocoelic
      cavity. These observations suggested that these endoplasmic-/Golgi-derived
      vesicles behave as active autophagic organelles presenting probably a maturation
      process from compact morulae to blastocyst. 

PMID- 25076425
TI  - Serologic survey on hantavirus in blood donors from the state of Santa Catarina,
      Brazil.
AB  - Emergent diseases such as Hantavirus Cardio-pulmonary Syndrome (HCPS) are able to
      create a significant impact on human populations due to their seriousness and
      high fatality rate. Santa Catarina, located in the South of Brazil, is the
      leading state for HCPS with 267 reported cases from 1999 to 2011. We present here
      a serological survey on hantavirus in blood donors from different cities of the
      state of Santa Catarina, with an IgG-ELISA using a recombinant nucleocapsid
      protein from Araraquara hantavirus as an antigen. In total, 314 donors from blood
      banks participated in the study, geographically covering the whole state. Among
      these, 14 individuals (4.4%) had antibodies to hantavirus: four of 50 (8%
      positivity) from Blumenau, four of 52 (7.6%) from Joinville, three of 50 (6%)
      from Florianopolis, two of 50 (4%) from Chapeco and one of 35 (2.8%) from
      Joacaba. It is possible that hantaviruses are circulating across almost the whole
      state, with important epidemiological implications. Considering that the
      seropositive blood donors are healthy individuals, it is possible that
      hantaviruses may be causing unrecognized infections, which are either
      asymptomatic or clinically nonspecific, in addition to HCPS. It is also possible
      that more than one hantavirus type could be circulating in this region, causing
      mostly benign infections. 

PMID- 25076423
TI  - Hepatocyte produced matrix metalloproteinases are regulated by CD147 in liver
      fibrogenesis.
AB  - BACKGROUND: The classical paradigm of liver injury asserts that hepatic stellate
      cells (HSC) produce, remodel and turnover the abnormal extracellular matrix (ECM)
      of fibrosis via matrix metalloproteinases (MMPs). In extrahepatic tissues MMP
      production is regulated by a number of mechanisms including expression of the
      glycoprotein CD147. Previously, we have shown that CD147 is expressed on
      hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we
      investigated if hepatocytes produce MMPs, regulated by CD147, which are capable
      of remodelling fibrotic ECM independent of the HSC. METHODS: Non-diseased,
      fibrotic and cirrhotic livers were examined for MMP activity and markers of
      fibrosis in humans and mice. CD147 expression and MMP activity were co-localised
      by in-situ zymography. The role of CD147 was studied in-vitro with siRNA to CD147
      in hepatocytes and in-vivo in mice with CCl4 induced liver injury using aCD147
      antibody intervention. RESULTS: In liver fibrosis in both human and mouse tissue
      MMP expression and activity (MMP-2, -9, -13 and -14) increased with progressive
      injury and localised to hepatocytes. Additionally, as expected, MMPs were
      abundantly expressed by activated HSC. Further, with progressive fibrosis there
      was expression of CD147, which localised to hepatocytes but not to HSC.
      Functionally significant in-vitro regulation of hepatocyte MMP production by
      CD147 was demonstrated using siRNA to CD147 that decreased hepatocyte MMP-2 and 
      9 expression/activity. Further, in-vivo alpha-CD147 antibody intervention
      decreased liver MMP-2, -9, -13, -14, TGF-beta and alpha-SMA expression in CCl4
      treated mice compared to controls. CONCLUSION: We have shown that hepatocytes
      produce active MMPs and that the glycoprotein CD147 regulates hepatocyte MMP
      expression. Targeting CD147 regulates hepatocyte MMP production both in-vitro and
      in-vivo, with the net result being reduced fibrotic matrix turnover in-vivo.
      Therefore, CD147 regulation of hepatocyte MMP is a novel pathway that could be
      targeted by future anti-fibrogenic agents.

PMID- 25076426
TI  - Prevalence of paracoccidioidomycosis infection by intradermal reaction in rural
      areas in Alfenas, Minas Gerais, Brazil.
AB  - This study aimed to estimate the prevalence of paracoccidioidal infection by
      intradermal reaction (Delayed-Type Hypersensitivity, DTH) to Paracoccidioides
      brasiliensis in rural areas in Alfenas, Southern Minas Gerais (MG) State, Brazil,
      and to assess risk factors (gender, occupation, age, alcohol intake and smoking)
      associated with infection. We conducted a population-based cross-sectional study
      using intradermal tests with gp 43 paracoccidioidin in 542 participants, who were
      previously contacted by local health agents and so spontaneously attended the
      test. Participants underwent an interview by filling out a registration form with
      epidemiological data and were tested with an intradermal administration of 0.1 mL
      of paracoccidioidin in the left forearm. The test was read 48 hours after
      injection and was considered positive if induration was greater than or equal to
      5 mm. Out of 542 participants, 46.67% were positive to the skin test. Prevalence
      increased in accordance with an increase of age. There was statistical
      significance only for males. Occupation, alcohol intake and smoking habits were
      not significantly associated with the risk of paracoccidioidomycosis infection.
      There is relevance of paracoccidioidomycosis infection in such rural areas, which
      suggests that further epidemiological and clinical studies on this mycosis should
      be done in the southern part of Minas Gerais State. 

PMID- 25076427
TI  - Determination of viral tropism by genotyping and phenotyping assays in Brazilian
      HIV-1-infected patients.
AB  - The clinical application of CCR5 antagonists involves first determining the
      coreceptor usage by the infecting viral strain. Bioinformatics programs that
      predict coreceptor usage could provide an alternative method to screen candidates
      for treatment with CCR5 antagonists, particularly in countries with limited
      financial resources. Thus, the present study aims to identify the best approach
      using bioinformatics tools for determining HIV-1 coreceptor usage in clinical
      practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected
      subjects under clinical monitoring were analyzed in this study. Based on the
      Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8%
      X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false
      positive rate of 10% gave the most suitable performance in this sampling: the R5
      and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and
      there was 78.6% concordance between the phenotypic and genotypic results. Further
      studies are needed to clarify how genetic diversity amongst virus strains affects
      bioinformatics-driven approaches for determining tropism. Although this strategy
      could be useful for screening patients in developing countries, some limitations
      remain that restrict the wider application of coreceptor usage tests in clinical
      practice. 

PMID- 25076428
TI  - Factors associated to adherence to different treatment schemes with meglumine
      antimoniate in a clinical trial for cutaneous leishmaniasis.
AB  - The favorable outcome of the treatment of a disease is influenced by the
      adherence to therapy. Our objective was to assess factors associated with
      adherence to treatment of patients included in a clinical trial of equivalence
      between the standard and alternative treatment schemes with meglumine antimoniate
      (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de
      Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a
      questionnaire to collect socioeconomic data. The following methods were used for
      adherence monitoring: counting of vial surplus, monitoring card, Morisky test and
      modified Morisky test (without the question regarding the schedule); we observed
      82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0%
      (modified Morisky test) adherence. There was a strong correlation between the
      method of vial counting and the monitoring card and modified Morisky test. A
      significant association was observed between greater adherence to treatment and
      low dose of MA, as well as with a lower number of people sleeping in the same
      room. We recommend the use of the modified Morisky test to assess adherence to
      treatment of CL with MA, because it is a simple method and with a good
      performance, when compared to other methods. 

PMID- 25076429
TI  - Participation of ticks in the infectious cycle of canine visceral leishmaniasis,
      in Teresina, Piaui, Brazil.
AB  - In this study, we detected Leishmania spp. infection in R. sanguineus collected
      from dogs that were naturally infected with L. (L.) infantum. We examined 35 dogs
      of both sexes and unknown ages. The infected dogs were serologically positive by
      the immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay
      (ELISA), and Quick Test-DPP (Dual Path Platform), as well as parasitological
      examination of a positive skin biopsy or sternal bone marrow aspiration. Ten
      negative dogs were included as controls. The ticks that infested these dogs were
      collected in pools of 10 adult females per animal. The PCR was performed with
      specific primers for Leishmania spp., which amplified a 720-bp fragment. Of the
      35 analyzed samples, a product was observed in eight samples (8/35; 22.9%). We
      conclude that the presence of parasite DNA suggests that ticks participate in the
      zoonotic cycle of canine visceral leishmaniasis, in the city of Teresina, Piaui. 

PMID- 25076430
TI  - Fungemia caused by Candida species in a children's public hospital in the city of
      Sao Paulo, Brazil: study in the period 2007-2010.
AB  - Candidemia remains a major cause of morbidity and mortality in the health care
      environment. The epidemiology of Candida infection is changing, mainly in
      relation to the number of episodes caused by species C. non-albicans. The overall
      objective of this study was to evaluate the frequency of yeasts of the genus
      Candida, in a four-year period, isolated from blood of pediatric patients
      hospitalized in a public hospital of the city of Sao Paulo, Brazil. In this
      period, yeasts from blood of 104 patients were isolated and, the identified
      species of Candida by phenotypic and genotypic methods were: C. albicans
      (39/104), C. tropicalis (25/104), C. parapsilosis (23/104), Pichia anomala
      (6/104), C. guilliermondii (5/104), C. krusei (3/104), C. glabrata (2/104) and C.
      pararugosa (1/104). During the period of the study, a higher frequency of
      isolates of C. non-albicans (63.55%) (p = 0.0286) was verified. In this study we
      verified the increase of the non-albicans species throughout the years (mainly in
      2009 and 2010). Thus, considering the peculiarities presented by Candida species,
      a correct identification of species is recommended to lead to a faster diagnosis
      and an efficient treatment. 

PMID- 25076431
TI  - Hepatitis B vaccination coverage and postvaccination serologic testing among
      medical students at a public university in Brazil.
AB  - The aim of this cross-sectional study was to determine the hepatitis B
      vaccination coverage among medical students at a public university in Rio de
      Janeiro, Brazil, and their compliance with the postvaccination serologic testing
      recommendations. Of the total of 858 students, 675 (78.7%) participated in the
      study. Among the participants, 48.9% (95% CI: 45.1% to 52.7%) were vaccinated
      against hepatitis B (received >= 3 doses of the vaccine), 31.6% were not
      (received 0, 1 or 2 doses), and 19.6% did not know their vaccination status.
      Hepatitis B vaccination coverage increased from 26.0% among first-year students
      to 70.6% among sixth-year students while the prevalence of unknown vaccination
      status decreased from 39.7% among first-year students to 2.4% among sixth-year
      students. The frequency of unvaccinated students ranged from 23.7% among fifth
      year students to 34.4% among first-year students. Only 34.8% of the vaccinated
      students performed the anti-HBs testing after vaccination. Among these medical
      students, we found a low adherence to the hepatitis B vaccination and to the
      postvaccination serologic testing. A comprehensive hepatitis B immunization
      program should be offered to students at this medical school. 

PMID- 25076432
TI  - Acute tubular necrosis and dengue.

PMID- 25076433
TI  - Susceptibility to antibiotics in urinary tract infections in a secondary care
      setting from 2005-2006 and 2010-2011, in Sao Paulo, Brazil: data from 11,943
      urine cultures.
AB  - INTRODUCTION: Urinary tract infection (UTI) has a high incidence and recurrence,
      therefore, treatment is empirical in the majority of cases. OBJECTIVES: The aim
      of this study was to analyze the urine cultures performed at a secondary
      hospital, during two periods, 2005-2006 and 2010-2011, and to estimate the
      microbial resistance. PATIENTS AND METHODS: We analyzed 11,943 aerobic urine
      cultures according to basic demographic data and susceptibility to antibiotics in
      accordance with the Clinical and Laboratory Standards Institute (CLSI) for Vitek
      1 and 2. RESULTS: Most of our cohort consisted of young adult females that were
      seen at the Emergency Department. E. coli was the most frequent (70.2%) among the
      75 species isolated. Resistance of all isolates was >= 20% for
      trimethoprim/sulfamethoxazole (TMP/SMX), norfloxacin, nitrofurantoin, cefazolin
      and nalidixic acid. Although E. coli was more susceptible (resistance >= 20% for
      TMP/SMX and nalidixic acid) among all of the isolates, when classified by the
      number and percentage of antibiotic resistance. Global resistance to
      fluoroquinolones was approximately 12%. Risk factors for E. coli were female
      gender and an age less than 65 years. Men and patients older than 65 years of
      age, presented more resistant isolates. Extended spectrum beta-lactamases (ESBL)
      were identified in 173 out of 5,722 Gram-negative isolates (3.0%) between 2010
      and 2011. CONCLUSION: E. coli was the most frequent microbe isolated in the urine
      cultures analyzed in this study. There was a significant evolution of bacterial
      resistance between the two periods studied. In particular, the rise of bacterial
      resistance to fluoroquinolones was concerning.

PMID- 25076434
TI  - Incidence of diarrhea by Clostridium difficile in hematologic patients and
      hematopoietic stem cell transplantation patients: risk factors for severe forms
      and death.
AB  - We describe the rate of incidence of Clostridium difficile-associated diarrhea
      (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC
      FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and
      1,000 days of neutropenia and the risk factors associated with the severe form of
      the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the
      detections of toxins A/B was used to identify C. difficile. A multivariate
      analysis was performed to evaluate potential factors associated with severe CDAD
      and death within 14 days after the diagnosis of CDAD, using multiple logistic
      regression. Sixty-six episodes were identified in 64 patients among 439 patients
      with diarrhea during the study period. CDA rate of incidence varied from 0.78 to
      5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days.
      The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64
      (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64
      (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of
      the patients (89%) received treatment with oral metronidazole and 19/64 (26%)
      died. The independent risk factors associated with death were the severe form of
      CDAD, and use of linezolid. 

PMID- 25076435
TI  - In vitro screening antibacterial activity of Bidens pilosa Linne and Annona
      crassiflora Mart. against oxacillin resistant Staphylococcus aureus (ORSA) from
      the aerial environment at the dental clinic.
AB  - Currently multiresistant Staphylococcus aureus is one common cause of infections
      with high rates of morbidity and mortality worldwide, which directs scientific
      endeavors in search for novel antimicrobials. In this study, nine extracts from
      Bidens pilosa (root, stem, flower and leaves) and Annona crassiflora (rind fruit,
      stem, leaves, seed and pulp) were obtained with ethanol: water (7:3, v/v) and
      their in vitro antibacterial activity evaluated through both the agar diffusion
      and broth microdilution methods against 60 Oxacillin Resistant S. aureus (ORSA)
      strains and against S. aureus ATCC6538. The extracts from B. pilosa and A.
      crassiflora inhibited the growth of the ORSA isolates in both methods. Leaves of
      B. pilosa presented mean of the inhibition zone diameters significantly higher
      than chlorexidine 0.12% against ORSA, and the extracts were more active against
      S. aureus ATCC (p < 0.05). Parallel, toxicity testing by using MTT method and
      phytochemical screening were assessed, and three extracts (B. pilosa, root and
      leaf, and A. crassiflora, seed) did not evidence toxicity. On the other hand, the
      cytotoxic concentrations (CC50 and CC90) for other extracts ranged from 2.06 to
      10.77 mg/mL. The presence of variable alkaloids, flavonoids, tannins and saponins
      was observed, even though there was a total absence of anthraquinones. Thus, the
      extracts from the leaves of B. pilosa revealed good anti-ORSA activity and did
      not exhibit toxicity. 

PMID- 25076436
TI  - Antimicrobial drug resistance in strains of Escherichia coli isolated from food
      sources.
AB  - A variety of foods and environmental sources harbor bacteria that are resistant
      to one or more antimicrobial drugs used in medicine and agriculture. Antibiotic
      resistance in Escherichia coli is of particular concern because it is the most
      common Gram-negative pathogen in humans. Hence this study was conducted to
      determine the antibiotic sensitivity pattern of E. coli isolated from different
      types of food items collected randomly from twelve localities of Hyderabad,
      India. A total of 150 samples comprising; vegetable salad, raw egg-surface, raw
      chicken, unpasteurized milk, and raw meat were processed microbiologically to
      isolate E. coli and to study their antibiotic susceptibility pattern by the Kirby
      Bauer method. The highest percentages of drug resistance in isolates of E. coli
      were detected from raw chicken (23.3%) followed by vegetable salad (20%), raw
      meat (13.3%), raw egg-surface (10%) and unpasteurized milk (6.7%). The overall
      incidence of drug resistant E. coli was 14.7%. A total of six (4%) Extended
      Spectrum beta-Lactamase (ESBL) producers were detected, two each from vegetable
      salads and raw chicken, and one each from raw egg-surface and raw meat. Multidrug
      resistant strains of E. coli are a matter of concern as resistance genes are
      easily transferable to other strains. Pathogen cycling through food is very
      common and might pose a potential health risk to the consumer. Therefore, in
      order to avoid this, good hygienic practices are necessary in the abattoirs to
      prevent contamination of cattle and poultry products with intestinal content as
      well as forbidding the use of untreated sewage in irrigating vegetables. 

PMID- 25076437
TI  - Experimental infection with Toxocara cati in pigs: migratory pattern and
      pathological response in early phase.
AB  - Experimental inoculations of approximately 100,000 infective Toxocara cati larval
      eggs were done in twelve pigs. The T. cati eggs used for inoculation were
      collected from cat's feces. Another group of three pigs served as an uninfected
      control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days
      post-inoculation (dpi). Tissue samples were taken for digestion and
      histopathology changes in early phase. The number of larvae recovered from the
      lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae
      of T. cati were present in the lymph nodes of the small and large intestine at
      seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other
      studied tissues, no larvae or less than one larva per gram was detected. The
      pathological response observed in the liver and lungs at seven and 14 dpi, showed
      white spots on the liver surface and areas of consolidation were observed in the
      lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi.
      In the liver we observed periportal and perilobular hepatitis. The lymph nodes of
      the intestines displayed eosinophil lymphadenitis with reactive centers
      containing parasitic forms in some of them. The granulomatous reaction was not
      observed in any tissues. The role of the other examined tissues had less
      significance. The relevance of this parasite as an etiological agent that leads
      to disease in paratenic hosts is evident. 

PMID- 25076438
TI  - Behavioral and memory changes in Mus musculus coinfected by Toxocara canis and
      Toxoplasma gondii.
AB  - Several researchers have stated that parasites can alter the behavior of their
      hosts, in order to increase the transmission rate, principally when prey-predator
      relationships are a reliable way of infection transmission. The aim of this study
      was to verify the occurrence of changes in anxiety and short-term memory patterns
      in experimentally infected Mus musculus by Toxocara canis and/or Toxoplasma
      gondii. Forty male Mus musculus (Balb/c) eight-week-old were divided into four
      groups of 10 mice each. One group was infected with 300 eggs of Toxocara canis; a
      second group was submitted to infection with 10 cysts of Toxoplasma gondii; a
      third group was concomitantly infected with both parasites with the same
      inoculums and the last group was maintained without infection. The anxiety levels
      were evaluated using an elevated plus maze and an actometer; the short-term
      memory was determined by a two-way active avoidance equipment. The determination
      of anxiety levels were conducted 40 and 70 days after infection and the short
      term memory was evaluated 140 days after infection. Mice chronically infected by
      Toxoplasma gondii showed impaired learning and short-term memory, but no
      significant differences were found in mice infected by Toxocara canis or
      concomitantly infected by Toxocara canis and Toxoplasma gondii when compared to
      non infected mice. 

PMID- 25076439
TI  - Molecular detection of Leishmania in phlebotomine sand flies in a cutaneous and
      visceral leishmaniasis endemic area in northeastern Brazil.
AB  - Several phlebotomine sand fly species have been regarded as putative or proven
      vectors of parasites of the genus Leishmania in Brazil, but data for the
      northeastern region remains incipient. In this study, a total of 600 phlebotomine
      sand flies were grouped in pools of 10 specimens each and tested by a Leishmania
      genus-specific PCR and by a PCR targeting Leishmania (Leishmania) infantum.
      Fourteen out of 60 pools were positive by the genus-specific PCR, being five
      pools of L. migonei, seven of L. complexa, one of L. sordellii and one of L.
      naftalekatzi, which correspond to a minimal infection rate of 2.3% (14/600). Our
      results, associated with their known anthropophily and their abundance, suggest
      the participation of L. migonei and L. complexa as vectors of Leishmania in
      northeastern Brazil. Remarkably, this is the first time in this country that the
      detection of Leishmania DNA in L. sordellii and L. naftalekatzi has been
      reported, but future studies are necessary to better understand the significance
      of these findings. 

PMID- 25076440
TI  - Resolution of cutaneous leishmaniasis after acute eczema due to intralesional
      meglumine antimoniate.
AB  - We report a case of a 42 year-old female, who came to a leishmaniasis reference
      center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in
      the right forearm. Treatment with low-dose intramuscular meglumine antimoniate
      (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although
      with the development of generalized eczema. After 87 days, the lesion worsened.
      Patient refused treatment with amphotericin B. MA was then infiltrated in the
      lesion, in two sessions, resulting in local eczema, with bullae formation;
      however, twenty days after, both the ulcer and eczema receded. Intralesional
      administration of MA should be used carefully when previous cutaneous
      hypersensitivity is detected. 

PMID- 25076442
TI  - Genetic diversity of measles virus--resurgence of new genotype D8 in Sao Paulo,
      Brazil.

PMID- 25076441
TI  - Molecular identification of Bartonella henselae in a seronegative cat scratch
      disease patient with AIDS in Rio de Janeiro, Brazil.
AB  - Bartonella henselae is associated with a wide spectrum of clinical
      manifestations, including cat scratch disease, endocarditis and
      meningoencephalitis, in immunocompetent and immunocompromised patients. We report
      the first molecularly confirmed case of B. henselae infection in an AIDS patient
      in state of Rio de Janeiro, Brazil. Although DNA sequence of B. henselae has been
      detected by polymerase chain reaction in a lymph node biopsy, acute and
      convalescent sera were nonreactive. 

PMID- 25076443
TI  - Human infection with avian influenza A (H7N9) virus.

PMID- 25076444
TI  - Facets of facelifting.

PMID- 25076445
TI  - Facelifting: anatomical considerations.
AB  - Facelifting techniques continue to evolve as our understanding of facial aging
      improves. Improved technology to affect changes on skin for tightening and volume
      restoration with fat grafting or fillers have improved results and safety for our
      patients. Success with facelifting and facial rejuvenation requires an
      understanding of the underlying anatomy and allows restoration of the anatomy to
      the younger more youthful status while avoiding complications. 

PMID- 25076446
TI  - Biplanar superficial musculoaponeurotic system imbrication rhytidectomy.
AB  - Rhytidectomy techniques have evolved significantly since the procedure's
      introduction in the early 20th century. Significant advancements in rhytidectomy
      techniques occurred in the 1960s and 1970s with the description of the subfascial
      rhytidectomy, the identification of the superficial musculoaponeurotic system
      (SMAS), and development of the SMAS flap. The incorporation of fascial
      undermining and suspension techniques have significantly improved the longevity
      and natural appearance of the facelift operation. More aggressive techniques
      including subperiosteal, composite, and deep plane techniques have been developed
      in the pursuit of the perfect facelift procedure. On the basis of over 25 years
      of clinical and surgical experience, a biplane SMAS imbrication rhytidectomy
      provides a natural, unstretched, and refreshed appearance resulting in high
      patient satisfaction. This article will present a detailed description of the
      rationale, technique, and nuances of the biplanar SMAS imbrication rhytidectomy.
      While the management of the platysma may vary depending on individual patient
      characteristics, the extent of subcutaneous, sub-SMAS, and neck dissection
      employed using the biplanar SMAS imbrication rhytidectomy minimizes patient
      complications and allows a relatively rapid recovery. 

PMID- 25076447
TI  - Deep plane facelifting for facial rejuvenation.
AB  - The purpose of this article is to provide the facial plastic surgeon with
      anatomical and embryologic evidence to support the use of the deep plane
      technique for optimal treatment of facial aging. A detailed description of the
      procedure is provided to allow safe and consistent performance. Insights into
      anatomical landmarks, technical nuances, and alternative approaches for facial
      variations are presented. The following points will be further elucidated in the
      article. The platysma muscle/submuscular aponeurotic system/galea are the
      continuous superficial cervical fascia encompassing the majority of facial fat,
      and this superficial soft tissue envelope is poorly anchored to the face. The
      deep cervical fascia binds the structural aspects of the face and covers the
      facial nerve and buccal fat pad. Facial aging is mainly due to gravity's long
      term effects on the superficial soft tissue envelope, with more subtle effects on
      the deeper structural compartments. The deep plane is the embryologic cleavage
      plane between these fascial layers, and is the logical place for facial
      dissection. The deep plane allows access to the buccal fat pad for treatment of
      jowling. Soft tissue mobilization is maximized in deep plane dissections and
      requires careful hairline planning. Flap advancement creates tension only at the
      fascia level allowing natural, tension-free skin closure, and long-lasting
      outcomes. The deep plane advancement flap is well vascularized and resistant to
      complications. 

PMID- 25076448
TI  - Laser-assisted facelift.
AB  - A variety of factors influence successful face and neck lift outcomes. Limited
      incision and/or dissection approaches as well as more traditional approaches
      impose certain limitations on surgeons' ability to effectively manage lower
      facial fullness and jowl ptosis. Laser-assisted facial contouring using a
      thermally confined 1,444 nm Nd:YAG micropulsed interstitial fiber laser enables
      precision volumetric reduction and shaping of lower facial fullness; the closed
      technique also predissects and facilitates greater vertical repositioning of an
      extended facelift flap. Use of the thermally confined 1,444 nm Nd:YAG micropulsed
      interstitial fiber laser in the neck (laser-assisted neck contouring) brings a
      similar benefit in predissecting, debulking, and shaping the neck and also
      significantly impacts surgical management of the platysma. This article focuses
      on methodology and benefits as well as limitations and complications of the laser
      assisted facelift. 

PMID- 25076449
TI  - Endoscopic-assisted facelifting.
AB  - Over the past two decades the use of endoscopes for facial rejuvenation gained
      wide popularity due to its reliable and reproducible results and limitation of
      the morbidity related to the open approaches. A thorough knowledge of the anatomy
      is of paramount importance to safely release all the fascial attachments while
      avoiding injuries to the facial nerve. The authors find the endoscopic forehead
      midface lift to be a reliable and safe procedure for facial rejuvenation. 

PMID- 25076450
TI  - Management of the aging forehead and brow.
AB  - The appearance of the forehead and brow conveys both a state of aging as well as
      the dynamic status of human emotion. Maintaining a youthful and pleasant
      appearance of this region is often integral to facial rejuvenation. Conditions
      that are often addressed include transverse rhytids and glabellar frown lines,
      ptotic eyebrows, skin deterioration, and volume loss. Surgical treatments to
      improve the forehead/brow might be open, endoscopic or combined. Common
      nonsurgical methods used to improve the region include neuromodulation, volume
      replacement, ablative and nonablative skin resurfacing, as well as phototherapy.
      Whatever treatments might be indicated, aim is to achieve optimum and natural
      looking results. 

PMID- 25076451
TI  - Complete corset platysmaplasty: evolution of addressing the aging neck.
AB  - Various techniques have been used to address the aging changes of the neck. This
      article reviews this evolution and describes the complete corset platysmaplasty
      procedure as the choice for optimal improvements in neck rejuvenation, especially
      when dealing with a "difficult neck." Evaluation and treatment of the aging neck
      must always be individualized and when the complete corset platysmaplasty is
      performed for those that are candidates, our experience shows greater immediate
      as well as long term satisfaction with less recurrence. 

PMID- 25076452
TI  - The difficult neck in facelifting.
AB  - The management of the neck often presents the most challenging aspect of the
      facelift procedure. The aesthetic neck has a well-defined jaw line, a pleasing
      and adequate cervicomental angle, and visible definitions of the deeper lateral
      and midline structures, such as the sternocleidomastoid muscles and trachea.
      Several unfavorable anatomic characteristics will present that will compound the
      challenge. These characteristics are contrasted with ideal features and include
      the following: an excess of adipose tissue, an excess of either thin or thick
      inelastic skin, marked relaxation of the suspension structures of the neck with
      resultant platysma banding and jowling, and unfavorable skeletal features such as
      microgenia and hyoid malposition. These patients present for rhytidectomy with
      inadequate chin projection, an obtuse cervicomental angle, sagging skin, and a
      heavy neck. To maximize rhytidectomy results in these patients with difficult
      neck anatomy, special attention to the anatomy and application of recognized
      techniques in an individualized manner is recommended. This article reviews the
      issues encountered in the management of the difficult neck in facelifting, with
      special attention given to patients with a heavy neck. 

PMID- 25076453
TI  - Direct cervicoplasty.
AB  - Rejuvenation of the aging neck is one of the common reasons for the patients
      presented to facial plastic surgeons. In the author's opinion, most of these
      patients will be best served by a full rhytidectomy approach with periauricular
      incisions, skin flap undermining, and platysmaplasty. There is a subset of
      patients, however, who presented with complaints limited to the so-called Turkey
      Gobbler deformity, and who do not wish to undergo a full rhytidectomy approach.
      These patients may be well served by a lesser procedure such as a direct
      cervicoplasty or submentoplasty. The advantages of this approach include shorter
      operative time, faster recovery, and lower complication rates. The primary
      disadvantage of these more limited approaches is that there is an anterior
      cervical scar that may be visible under some conditions. This article will review
      the multiple options for skin incisions as well as details of the technique that
      the authors have found may lead to a successful rejuvenation of the submental
      region. 

PMID- 25076454
TI  - Nonsurgical facial rejuvenation.
AB  - Facial rejuvenation has evolved from purely surgical to the use of nonsurgical
      techniques such as lasers and injectable fillers and toxins. This has occurred as
      a product of consumer demand for less down time and risk, as well as a new
      scientific knowledge of facial aging. A review of patient consultation evaluation
      and use of injectable products will be discussed in this chapter. 

PMID- 25076455
TI  - A peculiar case of facial congenital nevus.
AB  - Reconstruction of congenital nevi is difficult and challenging, but becomes even
      more so when they occur on the face due to functional and aesthetic reasons.
      Traditionally, these lesions have been treated with tissue expansion, sequential
      resection, and local flap closure with or without skin grafts. Here, we present a
      case reconstructing a large facial defect involving the entire cheek facial
      subunit following excision of a giant congenital nevus with a free anterolateral
      thigh flap. 

PMID- 25076456
TI  - Depressor septi nasi modifications in rhinoplasty: a review of anatomy and
      surgical techniques.
AB  - The anatomy of the nasal muscles contributes a social harmony in aesthetic
      rhinoplasty because these muscles coordinate the nose and the upper lip while
      smiling. Sometimes this coordination can be interrupted by the hyperactivity or
      variations of these muscles and may result as a deformity because of their
      dynamic functions and relations with the nose. In our daily practice, we usually
      perform the rhinoplasty without considering the dynamic functions. When the
      patients recover the muscle functions after operation and start to use their
      mimics, such as smiling, the undamaged dynamic forces may start to rotate the tip
      of the nose inferiorly in a long-term period, correlated with their preoperative
      function. To avoid this unexpected rotation it is essential to remember
      preoperative examination of the smile patterns. To manage this functional part of
      rhinoplasty, we aimed to clarify the smiling patterns or deformities mainly
      focused on depressor septi nasi muscle in this article. This muscle creates
      downward movement of the nasal tip and shortens the upper lip during smiling. The
      overactivity of this muscle can aggravate the smiling deformity in some patients
      by a sharper nasolabial angle correlated with levator labii superioris alaeque
      nasi and orbicularis oris muscle activities. The article not only stresses the
      correction of this deformity, but also aims to guide their treatment alternatives
      for correlation of postoperative results and applicability in rhinoplasty. 

PMID- 25076457
TI  - Revision rhinoplasty in ethnic patients: pollybeak deformity and persistent
      bulbous tip.
AB  - Pollybeak deformity has been reported as the most common complication of
      rhinoplasty surgery, occurring in some series in up to 50% of cases. Persistent
      bulbous tip after initial rhinoplasty is also a common complication; both lead to
      dissatisfaction with the esthetic result in many patients and are common
      complaints leading to subsequent revision rhinoplasty. In this retrospective
      review of 28 cases of revision rhinoplasty in ethnic patients, the most common
      indication for revision included pollybeak deformity and persistent bulbous tip.
      A majority of deformities were caused by poor implant selection and placement.
      Desirable esthetic results were often achieved by removal of existing grafts and
      replacement with custom-carved silicone implants. 

PMID- 25076458
TI  - Structural and electronic properties of the Pt(n)-PAH complex (n = 1, 2) from
      density functional calculations.
AB  - A detailed density functional study of the Pt atom and the Pt dimer adsorption on
      a polyaromatic hydrocarbon (PAH) is presented. The preferred adsorption site for
      a Pt atom is confirmed to be the bridge site. Upon adsorption of a single Pt
      atom, however, it is found here that the electronic ground state changes from the
      triplet state (5d(9)6s(1) configuration) to the closed-shell singlet state
      (5d(10)6s(0) configuration), which consequently will affect the catalytic
      activity of Pt when single Pt atoms bind to a carbon surface. The preferred
      adsorption site for the Pt dimer in the upright configuration is the hollow site.
      In contrast to the adsorption of a single Pt atom, the formation of a Pt-C bond
      in the adsorption of a Pt dimer is not accompanied by a change in the spin state,
      so the most stable electronic state is still the triplet state. While the atomic
      charge on the Pt atoms and dimers (in parallel configuration) in the Ptn-PAH
      complex is positive, a negative charge is found on the upper Pt atom for the
      upright configuration, indicating that single layers of Pt atoms will have a
      different catalytic activity as compared to Pt clusters on a carbon surface.
      Comparing the Pt-C bond length and the charge transfer on different sites, the
      magnitude of the charge transfer decreases with bond elongation, indicating that
      the catalytic activity of the Pt atom and dimer can be changed by modifying its
      chemical surroundings. The adsorption energy for the Pt dimer on a PAH surface is
      larger than that for two individual Pt atoms on the surface indicating that
      aggregation of Pt atoms on the PAH surface is favorable. 

PMID- 25076459
TI  - Photoinduced desorption of CO from rutile TiO2: elucidation of a new desorption
      mechanism using first principles.
AB  - Due to its high photocatalytic activity, TiO2 is of eminent interest for a
      manifold of applications ranging from surface catalysis up to solar energy
      conversion. However, the fundamental mechanisms of the underlying surface
      photochemistry are by no means understood. Focussing on this drawback, laser
      induced photodesorption of CO on an ideal rutile TiO2(110) surface is studied
      using first principles in terms of a model system. This paper presents both
      quantum chemical as well as quantum dynamical results, taking into account the
      desorption coordinate Z, the polar angle theta, and the azimuth angle phi of the
      adsorbate. Detailed insight into the fundamental mechanisms of the
      photodesorption process in this model system is obtained, and a new desorption
      scenario is elucidated. 

PMID- 25076460
TI  - Uncommon presentation of pityriasis rosea after yellow fever inoculation.

PMID- 25076461
TI  - Efficient optical resolution of water-soluble self-assembled tetrahedral M4L6
      cages with 1,1'-bi-2-naphthol.
AB  - In this paper, a water-soluble racemic self-assembled tetrahedral cage [Fe4L6](4
      ) was successfully resolved into their DeltaDeltaDeltaDelta and
      LambdaLambdaLambdaLambda enantiomers by (R)-/(S)-1,1'-bi-2-naphthol. The
      enantiomeric excess of the resolved Fe(II) cage was 99%.

PMID- 25076462
TI  - Clinical relevance of magnetic resonance imaging in cervical spine clearance: a
      prospective study.
AB  - IMPORTANCE: A missed cervical spine (CS) injury can have devastating
      consequences. When CS injuries cannot be ruled out clinically using the National
      Emergency X-Radiography Utilization Study low-risk criteria because of either a
      neurologic deficit or pain, the optimal imaging modality for CS clearance remains
      controversial. OBJECTIVE: To investigate the accuracy of computed tomography (CT)
      and magnetic resonance imaging (MRI) for CS clearance. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective observational study was conducted from January 1,
      2010, through May 31, 2011, at a level I trauma center. Participants included 830
      adults who were awake, alert, and able to be examined who experienced blunt
      trauma with resultant midline CS tenderness and/or neurologic deficits and were
      undergoing CT of the CS. Initial examinations, all CS imaging results,
      interventions, and final CS diagnoses were documented. The criterion standard for
      the sensitivity and specificity calculations was final diagnosis of CS injury at
      the time of discharge. MAIN OUTCOMES AND MEASURES: Clinically significant CS
      injuries, defined as injuries requiring surgical stabilization or halo placement.
      RESULTS: Overall, 164 CS injuries (19.8%) were diagnosed, and 23 of these (2.8%)
      were clinically significant. All clinically significant injuries were detected by
      CT. Fifteen of 681 patients (2.2%) with a normal CT scan had a newly identified
      finding on MRI; however, none of the injuries required surgical intervention or
      halo placement. There was no change in management on the basis of MRI findings.
      The sensitivity and specificity of CT for detecting CS injury was 90.9% and 100%,
      respectively. For clinically significant CS injuries, the sensitivity was 100%
      and specificity was 100%. CONCLUSIONS AND RELEVANCE: Computed tomography is
      effective in the detection of clinically significant CS injuries in adults deemed
      eligible for evaluation who had a neurologic deficit or CS pain. Magnetic
      resonance imaging does not provide any additional clinically relevant
      information.

PMID- 25076463
TI  - Real-world experience with once-daily gabapentin for the treatment of
      postherpetic neuralgia (PHN).
AB  - OBJECTIVES: To evaluate the safety and effectiveness of once-daily
      gastroretentive gabapentin (G-GR) for the treatment of postherpetic neuralgia in
      real-world clinical practice. MATERIALS AND METHODS: Patients aged 18 years and
      above were divided into 2 cohorts: patients aged 70 years and below and patients
      above 70 years. All patients were titrated to 1800 mg G-GR/d over 2 weeks and
      maintained at that dosage for 6 weeks, for 8 weeks total treatment. To reflect
      clinical practice, exclusion criteria were limited to those in the product label.
      Efficacy was assessed using a visual analog scale (VAS) and the Brief Pain
      Inventory. Patient/Clinician Global Impression of Change scales were completed at
      week 8. Adverse events (AEs) were assessed. RESULTS: The efficacy population
      included 190 patients (110, 70 y and below; 80, above 70 y). The mean percent
      change in VAS score at week 8 from baseline was -21.3%/-20.4% (70 y and
      below/above 70 y). The proportion of patients with a >=30% reduction in VAS score
      from baseline was 51.8%/55.0% (70 y and below/above 70 y) and was 42.7%/37.5% for
      a >=50% reduction. Brief Pain Inventory scores were all significantly reduced by
      week 8. On the Patient Global Impression of Change instrument, more patients aged
      70 years and below reported feeling "much" or "very much" improved from baseline
      (59.0% vs. 40.3%). G-GR was generally well tolerated. Thirty-seven (18.8%)
      patients experienced AEs that led to discontinuation. No patients died and 5
      (2.5%) patients experienced serious AEs. The most common G-GR-related AEs (70 y
      and below/above 70 y) were dizziness (11.7%/16.3%) and somnolence (3.6%/8.1%).
      DISCUSSION: In real-world clinical practice, G-GR seems to be an effective, well
      tolerated treatment option for patients with postherpetic neuralgia, regardless
      of age.

PMID- 25076466
TI  - Endorsement of reporting guidelines is our next step.

PMID- 25076464
TI  - Comparison of the performances of copeptin and multiple biomarkers in long-term
      prognosis of severe traumatic brain injury.
AB  - Enhanced blood levels of copeptin correlate with poor clinical outcomes after
      acute critical illness. This study aimed to compare the prognostic performances
      of plasma concentrations of copeptin and other biomarkers like myelin basic
      protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase,
      phosphorylated axonal neurofilament subunit H, Tau and ubiquitin carboxyl
      terminal hydrolase L1 in severe traumatic brain injury. We recruited 102 healthy
      controls and 102 acute patients with severe traumatic brain injury. Plasma
      concentrations of these biomarkers were determined using enzyme-linked
      immunosorbent assay. Their prognostic predictive performances of 6-month
      mortality and unfavorable outcome (Glasgow Outcome Scale score of 1-3) were
      compared. Plasma concentrations of these biomarkers were statistically
      significantly higher in all patients than in healthy controls, in non-survivors
      than in survivors and in patients with unfavorable outcome than with favorable
      outcome. Areas under receiver operating characteristic curves of plasma
      concentrations of these biomarkers were similar to those of Glasgow Coma Scale
      score for prognostic prediction. Except plasma copeptin concentration, other
      biomarkers concentrations in plasma did not statistically significantly improve
      prognostic predictive value of Glasgow Coma Scale score. Copeptin levels may be a
      useful tool to predict long-term clinical outcomes after severe traumatic brain
      injury and have a potential to assist clinicians. 

PMID- 25076467
TI  - Visual outcomes after implantation of a novel refractive toric multifocal
      intraocular lens.
AB  - PURPOSE: To assess the postoperative outcomes of a novel toric multifocal in
      traocular lens (IOL) in patients with cataract and corneal astigmatism. METHODS:
      This prospective nonrandomized study included patients with cataract, corneal
      astigmatism, and a motivation for spectacle independence. In all patients, a
      Rayner M-flex(r) T toric IOL was implanted in the capsular bag. Three months
      after surgery, the distance, intermediate, and near visual acuities; spherical
      equivalent; residual refractive astigmatism; defocus curve; and contrast
      sensitivity were evaluated. A patient satisfaction and visual phenomena
      questionnaire was administered to all patients. RESULTS: Thirty-four eyes of 18
      patients were included in this study. Three months after surgery, the mean
      corrected distance visual acuity (logMAR) was 0.00 +/- 0.08 at 6 m, 0.20 +/- 0.09
      at 70 cm, and 0.08 +/- 0.11 at 40 cm. Uncorrected distance vision acuity was
      20/40 or better in 100% eyes. The preoperative mean refractive cylinder (RC) was 
      2.19 (SD: +/- 0.53). After a 3-month follow-up, the average RC was -0.44 D (SD:
      +/- 0.27; p<0.001). Contrast sensitivity levels were high. At the last follow-up,
      87.5% patients were spectacle-independent for near, intermediate, and distance
      vision, and approximately 44% patients reported halos and glare. CONCLUSION:
      Toric multifocal IOL implantation in patients with cataract and corneal
      astigmatism using the Rayner M-flex(r) T toric IOL was a simple, safe, and
      accurate option. This technology provides surgeons with a feasible option for
      meeting patient expectations of an enhanced lifestyle resulting from decreased
      spectacle dependence.

PMID- 25076468
TI  - Artificial pupil versus contralateral balanced contact lens fit for presbyopia
      correction.
AB  - PURPOSE: To assess and compare the effects of contact lens-based artificial pupil
      design and contralateral balanced multifocal contact lens combination (CBMCLC) on
      visual performance. METHODS: This randomized crossover study conducted at the
      University of Valencia, Spain included 38 presbyopic patients using an artificial
      pupil contact lens in the nondominant eye and a CBMCLC. After a month of lens
      wear, the binocular distance visual acuity (BDVA), binocular near visual acuity
      (BNVA), defocus curve, binocular distance, and near contrast sensitivity and near
      stereoacuity (NSA) were measured under photopic conditions (85 cd/m2). Moreover,
      BDVA and binocular distance contrast sensitivity were examined under mesopic
      conditions (5 cd/m2). RESULTS: Visual acuity at an intermediate distance and near
      vision was better with the CBMCLC than with the artificial pupil (p<0.05).
      Statistically significant differences were found in contrast sensitivity between
      the two types of correction for distance (under mesopic conditions) and for near
      vision, with the CBMCLC exhibiting better results in both cases (p<0.05). The
      mean NSA values obtained for the artificial pupil contact lens were significantly
      worse than those for the CBMCLC (p=0.001). CONCLUSION: The CBMCLC provided
      greater visual performance in terms of intermediate and near vision compared with
      the artificial pupil contact lens.

PMID- 25076469
TI  - Metallic corneal foreign bodies: an occupational health hazard.
AB  - PURPOSE: To analyze the risk factors, outcomes, demographic characteristics, and
      attitudes of workers with metallic corneal foreign body (FB) injury. METHODS: One
      hundred consecutive patients who presented with a metallic corneal FB to the eye
      clinic at Diyarbakir Training and Research Hospital were evaluated. The patients
      completed a questionnaire and were examined to determine features of the injury.
      RESULTS: All patients were male. The mean age was 32.46 +/- 1.03 years. Fifty
      five percent of the patients were unregistered workers, 59% were working in the
      metal industry sector, and 65% injuries resulted from metal cutting. Protective
      goggles were available in the workplace of 64% patients. However, 57% patients
      were not wearing goggles when the accident occurred, and 43% were injured despite
      goggle use. Most patients (52%) attempted to remove FBs by themselves. FBs were
      located in the central zone of the cornea in 16% patients. Rust marks remained
      after FB removal in 26% patients. Corneal scars from previous FB injuries were
      present in 58% patients. Only 8% workplaces provided compensation for physician
      visits for occupation related illnesses. CONCLUSIONS: Workplaces with a high risk
      for eye injuries should increase their protective measures, and educational
      programs should be implemented for both workers and occupational physicians. The
      government should enforce laws regarding unregistered workers in a better manner.

PMID- 25076470
TI  - Changes in corneal sensitivity following cross-linking for progressive early
      stage keratoconus.
AB  - PURPOSE: To evaluate changes in corneal sensitivity following corneal cross
      linking (CXL) in patients with progressive earlier stage keratoconus. METHODS:
      Thirty-eight eyes of 19 patients (11 women, 8 men) were included in a
      prospective, nonrandomized clinical study. The mean patient age was 22 years
      (range, 18-26 years). Inclusion criteria were early stage bilateral progressive
      keratoconus, a transparent cornea, and a thickness of >=440 um in the thinnest
      area of the cornea. Using the Cochet-Bonnet esthesiometer, central corneal
      sensitivity was measured before surgery, 7 days after surgery, and once a month
      thereafter until recovery of baseline preoperative levels. Central corneal
      sensitivity >40 mm was considered normal. RESULTS: Corneal sensitivity gradually
      returned to preoperative levels in all treated eyes. The mean central corneal
      sensitivity was 52.2, 24.0, 38.2, 42.5, 50.0, and 52.5 mm before surgery, 7 days
      after surgery, and at 1, 2, 3, and 4 months after surgery, respectively. Normal
      levels of corneal sensation, but not baseline (preoperative) levels, were
      observed 2 months after surgery. The preoperative levels were observed 3 months
      after surgery. CONCLUSIONS: Our results suggest that central corneal sensitivity
      can be decreased for as long as 3 months after CXL for progressive earlier stage
      keratoconus.

PMID- 25076471
TI  - The influence of body position on Bielschowsky's test.
AB  - PURPOSE: To investigate the veracity of Jampolsky's statement that Bielschowsky's
      head tilt test is inverted if performed with the patient in the upside-down
      position and to interpret its neuromuscular mechanism. METHODS: We present a
      series of 10 patients selected from a referred sample who were diagnosed with
      superior oblique paresis. Hypertropia was measured in the primary position, with
      the head erect and tilted toward both shoulders with the patient in the erect,
      supine, and upside-down positions. The last position was achieved by hanging the
      patient upside-down. RESULTS: As expected, our results showed the veracity of
      Jampolsky's statement. The forced head tilt difference was inverted or
      significantly decreased when the test was performed in the upside-down position.
      Moreover, in all patients, Bielschowsky's phenomenon was neutralized in the
      supine body position, in which hypertropia with the head erect tended to vanish.
      In 3 patients, it disappeared completely. CONCLUSIONS: This study showed that, in
      patients with superior oblique paresis, differences in the extent of hypertropia
      in Bielschowsky's test tended to vanish when the test was performed with the
      patient in the supine position and invert when it was performed with the patient
      in the upside-down position.

PMID- 25076472
TI  - Optical and nonoptical aids for reading and writing in individuals with acquired
      low vision.
AB  - PURPOSE: To evaluate the use of optical and nonoptical aids during reading and
      writing activities in individuals with acquired low vision. METHODS: This study
      was performed using descriptive and cross-sectional surveys. The data collection
      instrument was created with structured questions that were developed from an
      exploratory study and a previous test based on interviews, and it evaluated the
      following variables: personal characteristics, use of optical and nonoptical
      aids, and activities that required the use of optical and nonoptical aids.
      RESULTS: The study population included 30 subjects with acquired low vision and
      visual acuities of 20/200-20/400. Most subjects reported the use of some optical
      aids (60.0%). Of these 60.0%, the majority (83.3%) cited spectacles as the most
      widely used optical aid. The majority (63.3%) of subjects also reported the use
      of nonoptical aids, the most frequent ones being letter magnification (68.4%),
      followed by bringing the objects closer to the eyes (57.8%). Subjects often used
      more than one nonoptical aid. CONCLUSIONS: The majority of participants reported
      the use of optical and nonoptical aids during reading activities, highlighting
      the use of spectacles, magnifying glasses, and letter magnification; however,
      even after the use of these aids, we found that the subjects often needed to read
      the text more than once to understand it. During writing activities, all subjects
      reported the use of optical aids, while most stated that they did not use
      nonoptical aids for such activities.

PMID- 25076473
TI  - Vision-related quality of life in patients after ocular penetrating injuries.
AB  - PURPOSE: To measure and investigate visual functioning and health-related quality
      of life (QOL) in patients after ocular penetrating injuries (OPI). METHODS: Fifty
      four adult patients with OPI and 26 healthy control subjects were enrolled in the
      study. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25)
      and the 36-Item Short Form Health Survey (SF 36) were administered.
      Sociodemographic and clinical data also were collected. The primary outcome
      measures were comparisons and multivariate analysis among groups for the NEI VFQ
      25 and SF 36 subscale scores. RESULTS: All NEI VFQ-25 scores, except general
      health, were significantly lower in the OPI group than those in the control
      group. All SF 36 scores were significantly lower in the OPI group than in the
      control group. The NEI VFQ-25 subscale item scores showed no significant
      differences with respect to age, educational level, or visual acuity in the
      injured eye. The SF 36 subscale item scores revealed no significant differences
      according to gender or educational level. CONCLUSIONS: Patients with OPI have
      increased psychological symptoms and lower levels of QOL than healthy control
      subjects have. Deteriorations in QOL should be kept in mind when managing
      patients with OPI.

PMID- 25076474
TI  - Artificial tears alone versus 0.45% ketorolac tromethamine with artificial tears
      for the treatment of acute viral conjunctivitis.
AB  - PURPOSE: To evaluate the effects of preservative-free 0.45% ketorolac
      tromethamine and artificial tears (carboxymethylcellulose) compared with those of
      preservative-free artificial tears alone on the symptoms and signs of acute viral
      conjunctivitis. METHODS: This was a randomized, double-masked clinical trial that
      included 50 patients who were diagnosed with acute viral conjunctivitis and
      distributed into two groups (Group 0: artificial tears and Group 1: 0.45%
      ketorolac tromethamine + carboxymethylcellulose). The patients were instructed to
      use the medication 4 times daily. Signs (conjunctival hyperemia, chemosis,
      follicles, and secretion) and symptoms (general ocular discomfort, itching,
      foreign body sensation, tearing, redness, and swelling of the eyelids) were
      scored at baseline and on the third and seventh days of treatment using a
      standardized questionnaire and slitlamp anterior segment examination. RESULTS:
      Both groups showed an improvement in the signs and symptoms of conjunctivitis in
      their follow-up visits. There was no significant difference in symptom and sign
      scores between Group 0 and Group 1 in the study visits (p>0.05). The frequency of
      side effects during treatment was similar between groups (p>0.05). CONCLUSIONS:
      Our findings indicate that 0.45% ketorolac tromethamine was not superior to the
      use of artificial tears in relieving the signs and symptoms of viral
      conjunctivitis.

PMID- 25076475
TI  - Implantable collamer lens and femtosecond laser for myopia: comparison using an
      adaptive optics visual simulator.
AB  - PURPOSE: To compare optical and visual quality of implantable collamer lens (ICL)
      implantation and femtosecond laser in situ keratomileusis (F-LASIK) for myopia.
      METHODS: The CRX1 adaptive optics visual simulator (Imagine Eyes, Orsay, France)
      was used to simulate the wavefront aberration pattern after the two surgical
      procedures for -3-diopter (D) and -6-D myopia. Visual acuity at different
      contrasts and contrast sensitivities at 10, 20, and 25 cycles/degree (cpd) were
      measured for 3-mm and 5-mm pupils. The modulation transfer function (MTF) and
      point spread function (PSF) were calculated for 5-mm pupils. RESULTS: F-LASIK MTF
      was worse than ICL MTF, which was close to diffraction-limited MTF. ICL cases
      showed less spread out of PSF than F-LASIK cases. ICL cases showed better visual
      acuity values than F-LASIK cases for all pupils, contrasts, and myopic treatments
      (p<0.05). No statistically significant differences were found in contrast
      sensitivities between ICL and F-LASIK cases with -3-D myopia for both pupils for
      all evaluated spatial frequencies (p>0.05). For -6-D myopia, however,
      statistically significant differences in contrast sensitivities were found for
      both pupils for all evaluated spatial frequencies (p<0.05). Contrast
      sensitivities were better after ICL implantation than after F-LASIK. CONCLUSIONS:
      ICL implantation and F-LASIK provide good optical and visual quality, although
      the former provides better outcomes of MTF, PSF, visual acuity, and contrast
      sensitivity, especially for cases with large refractive errors and pupil sizes.
      These outcomes are related to the F-LASIK producing larger high-order
      aberrations.

PMID- 25076476
TI  - Quality of life of patients with strabismus.
AB  - PURPOSE: To evaluate the impact of strabismus on quality of life. METHODS: This
      cross-sectional study included 101 individuals aged 7-67 years with strabismus.
      They were interviewed and made to answer a questionnaire with 20 questions
      intended to assess the individual's interaction with their social and working
      environment, sensory perception, and limitations in their daily lives. There were
      five types of possible responses for each question: never, rarely or very few
      times, sometimes, frequently, and always. The questionnaire was based on the AS
      20 and contained 11 questions assessing psychosocial aspects and 9 questions
      assessing functional aspects. Among those who were interviewed, 24.8% had
      undergone surgical correction of strabismus. RESULTS: We observed a significant
      impact of strabismus on the quality of life of the interviewed individuals.
      Feelings of sadness and inferiority because of strabismus were reported by 74.2%
      and 58.4% respondents, respectively. In terms of functionality, 12.1% reported
      difficulty in reading, 14% said they had difficulty in depth perception
      (stereopsis), and 17.8% frequently or always associated pain or burning sensation
      in the eyes to strabismus. A significant difference was detected in the quality
      of life scores for the psychosocial aspect among patients who had and had not
      undergone surgery (Wilcoxon test, 158; p<0.001). Individuals who had undergone
      surgery had a better quality of life from the psychosocial perspective.
      CONCLUSIONS: In this evaluation, we found a significant negative interference of
      strabismus on quality of life from both the functional and psychosocial
      perspectives. This demonstrated the importance of treatment for strabismus,
      regardless of age, because it can interfere with the functional well-being of the
      individual.

PMID- 25076477
TI  - Congenital simple hamartoma of the retinal pigment epithelium: a case report.
AB  - We report the case of a 56-year-old woman who presented for a routine
      ophthalmological examination without visual symptoms and had a unilateral black
      retinal lesion that was detected by clinical examination. Fluorescein angiography
      and optical coherence tomography findings were compatible with a congenital
      simple hamartoma of the retinal pigment epithelium. It is very important to
      detect this tumor and differentiate it from other pigmented fundus lesions that
      can compromise visual function or result in systemic conditions such as those
      caused by malignant tumors. 

PMID- 25076478
TI  - Medial rectus muscle myositis as an atypical presentation of mucosa-associated
      lymphatic tissue lymphoma: a case report.
AB  - Here we describe the rare case of a 55-year-old man with medial rectus muscle
      myositis as an atypical presentation of non-Hodgkin B-cell mucosa-associated
      lymphoma (MALT). Pathology and immunohistochemistry of the affected muscle
      confirmed the diagnosis of a neoplasm. The primary etiology of orbital myositis
      is Graves' ophthalmopathy, but several other diseases may cause this clinical
      presentation. Therefore, the neoplastic causes must be eliminated from the
      differential diagnoses. non-Hodgkin B-cell mucosa-associated lymphoma is the most
      common histological type of lymphoma in the orbit, with the conjunctiva and
      lacrimal glands being the most commonly affected sites. However, it may also
      present in atypical forms involving others sites and tissues. 

PMID- 25076479
TI  - Keratectasia following laser in situ keratomileusis in a low-risk patient with
      benign joint hypermobility syndrome.
AB  - Here we present the case of a 27-year-old woman with benign joint hypermobility
      (BJHS) syndrome who developed keratectasia after laser in situ keratomileusis
      (LASIK) in both eyes. Both eyes had identical low Randleman risk factor scores.
      To our knowledge, this is the first report of such a complication in a patient
      with BJHS. It highlights our incomplete knowledge of the risk factors for
      keratectasia following LASIK and suggests that BJHS should be considered as a
      risk factor for keratectasia.

PMID- 25076480
TI  - In vivo ultrathin Descemet stripping automated endothelial keratoplasty with a
      low-energy and high-frequency femtosecond laser.
AB  - This case report describes the production of an ultrathin endothelial donor
      corneal lamella using a femtosecond laser with low energy and a high frequency.
      In addition, we report its use in vivo in an eye with pseudophakic bullous
      keratopathy. The outcomes were observed 3 months after surgery in terms of the
      change in endothelial donor lamella and full cornea thickness (including
      pachymetric mapping), visual acuity, and endothelial cell count.

PMID- 25076481
TI  - Surgical management of astigmatism with toric intraocular lenses.
AB  - Correction of corneal astigmatism is a key element of cataract surgery, since
      post-surgical residual astigmatism can compromise the patient's uncorrected
      visual acuity. Toric intraocular lenses (IOLs) compensate for corneal astigmatism
      at the time of surgery, correcting ocular astigmatism. They are a predictable
      treatment. However, accurate measurement of corneal astigmatism is mandatory for
      choosing the correct toric IOL power and for planning optimal alignment. When
      calculating the power of toric IOLs, it is important to consider anterior and
      posterior corneal astigmatism, along with the surgically induced astigmatism.
      Accurate toric lens alignment along the calculated meridian is also crucial to
      achieve effective astigmatism correction. There are several techniques to guide
      IOL alignment, including the traditional manual marking technique and automated
      systems based on anatomic and topographic landmarks. The aim of this review is to
      provide an overview on astigmatism management with toric IOLs, including relevant
      patient selection criteria, corneal astigmatism measurement, toric IOL power
      calculation, toric IOL alignment, clinical outcomes and complications.

PMID- 25076482
TI  - Use of the Iowa Satisfaction with Anesthesia Scale in Portuguese.

PMID- 25076483
TI  - Plagiarism and misconduct in research.

PMID- 25076484
TI  - Multiple time courses of salivary alpha-amylase and dimensions of affect in
      adolescence.
AB  - Previous research has illustrated associations among daily experiences, emotions
      and stress-responding physiological systems. Recently, investigators have
      examined salivary alpha-amylase (sAA), a surrogate marker of the autonomic
      nervous system, and its associations with affect. The current study examined
      associations among affective valence, arousal and sAA across three different time
      courses at the momentary, daily and inter-individual level to understand varying
      influences of adolescents' daily emotional experiences on sAA reactivity and
      diurnal sAA activity. Adolescents (N=82) provided salivary samples and diary
      reports of affect and experiences five times a day for three consecutive days.
      They also completed self-report questionnaires on trait affect. Findings from
      multilevel growth curves demonstrated that adolescents in our sample displayed
      typical sAA diurnal rhythms with levels dropping 30 min after waking and then
      increasing across the day to a peak in the late afternoon. Within person
      momentary experiences of high arousal positive affect were associated with
      momentary sAA reactivity. Prior day experiences of high arousal negative affect
      were associated with a greater amylase awakening response (i.e., greater
      decrease) and flatter slopes the next day. Trait positive affect was also
      associated with flatter sAA slopes. Our findings suggest that both affective
      arousal and valence should be accounted for when examining differences in sAA
      reactivity and diurnal patterns. Further, our results indicated that emotion
      physiology transactions among adolescents occur over varying time scales for
      salivary alpha-amylase as well as cortisol.

PMID- 25076485
TI  - Toll-like receptor signaling directly increases functional IL-17RA expression in
      neuroglial cells.
AB  - IL-17, the hallmark cytokine of Th17 cells, plays a pivotal role in the
      pathogenesis of autoimmune diseases, including encephalomyelitis. In the central
      nervous system, neuroglial cells are the main residents that express IL-17R and
      respond to IL-17 by producing chemokines/cytokines and boosting local
      inflammation. Factors that influence the IL-17R expression in neuroglial cells
      can also exert their impacts on the outbreak, progression and outcome of
      encephalomyelitis. Here, we reported that Toll-like receptor signaling has its
      bias for promoting the IL-17RA, but not the IL-17RC, expression in mouse
      neuroglial cells in a T cell infiltration independent manner. Elevated IL-17R
      functionally responded to IL-17 by secreting more chemokines and accelerating CD4
      cell migration. First, real-time PCR confirmed that the expression of Il-17ra,
      but not Il-17rc, was significantly increased in the brain and spinal cord of EAE
      induced mice. This effect was elicited by something in complete Freund's adjuvant
      (CFA), because markedly increased IL-17R was detected in mice immunized with CFA
      only, even though no evidence of EAE was found. Furthermore, in Rag1(-/-) mice,
      it was confirmed that CFA could augment the IL-17RA expression in the CNS in the
      absence of T cell infiltration. In vivo immunization with TLR ligands and in
      vitro treatment of purified neuroglial cells demonstrated that TLR ligands
      directly and effectively evoke the IL-17RA expression in the CNS and in cultured
      astrocytes, microglia and oligodendrocytes. LPS was the most effective inducer of
      the IL-17RA expression in astrocytes, and polyIC was superior to LPS for
      microglia and oligodendrocytes. Activated CD4 cells can also promote the
      secretion of chemokines by LPS pre-treated astrocytes, and hence accelerate the
      migration of CD4 cells, which was blocked by the neutralization of IL-17RA on the
      surface of the astrocyte. Taken together, we concluded that TLR signaling can
      directly stimulate the expression of IL-17RA, but not IL-17RC, in neuroglial
      cells, which functionally respond to IL-17A by secreting chemokines, accelerating
      CD4 cell migration, and contributing to the pathogenesis of encephalomyelitis.

PMID- 25076486
TI  - Genetic analysis among environmental strains of Balamuthia mandrillaris recovered
      from an artificial lagoon and from soil in Sonora, Mexico.
AB  - Since the first report of Balamuthia mandrillaris as a causative agent of
      granulomatous amoebic encephalitis in humans, the environmental niche of this
      amoeba was assumed to be restricted to soil and dust. A single isolation from
      water was recently made independently by us from Northern Mexico. Now we report
      the isolation of 8 new strains of B. mandrillaris from Mexico. This continues the
      pattern of an excess of isolates from North America, compared to other parts of
      the world. All of the new isolates are environmental isolates, 7 from water
      samples and one from soil. The identity of each isolate was confirmed by PCR and
      by examining the sequences of the mitochondrial 16S-like rRNA gene. Success in
      amplification was determined using comparisons of amplifications of DNA from the
      strain CDC: V039 and the water strain (ITSON-BM1) as positive controls. The DNA
      sequences of the new isolates were compared to older strains from clinical cases
      using phylogenetic analysis, showing very high sequence similarity. The
      similarity among the new isolates and with previous clinical and environmental
      isolates of B. mandrillaris was also examined using biochemical and immunological
      studies. High homogeneity of total protein products, and similarity in antigenic
      moiety among the eight new isolates and two controls was found. Taken together,
      the molecular and biochemical studies indicate very low levels of genetic
      variation within B. mandrillaris. 

PMID- 25076487
TI  - High-accuracy brain-machine interfaces using feedback information.
AB  - Sensory feedback is very important for movement control. However, feedback
      information has not been directly used to update movement prediction model in the
      previous BMI studies, although the closed-loop BMI system provides the visual
      feedback to users. Here, we propose a BMI framework combining image processing as
      the feedback information with a novel prediction method. The feedback-prediction
      algorithm (FPA) generates feedback information from the positions of objects and
      modifies movement prediction according to the information. The FPA predicts a
      target among objects based on the movement direction predicted from the neural
      activity. After the target selection, the FPA modifies the predicted direction
      toward the target and modulates the magnitude of the predicted vector to easily
      reach the target. The FPA repeats the modification in every prediction time
      points. To evaluate the improvements of prediction accuracy provided by the
      feedback, we compared the prediction performances with feedback (FPA) and without
      feedback. We demonstrated that accuracy of movement prediction can be
      considerably improved by the FPA combining feedback information. The accuracy of
      the movement prediction was significantly improved for all subjects (P<0.001) and
      32.1% of the mean error was reduced. The BMI performance will be improved by
      combining feedback information and it will promote the development of a practical
      BMI system. 

PMID- 25076488
TI  - Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.
AB  - BACKGROUND: Anti-inflammation via inhibition of NF-kappaB pathways in hepatic
      stellate cells (HSCs) is one therapeutic approach to hepatic fibrosis. Tanshinone
      IIA (C19H18O3, Tan IIA) is a lipophilic diterpene isolated from Salvia
      miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether
      Tan IIA could inhibit HSC activation. MATERIALS AND METHODS: The cell line of rat
      hepatic stellate cells (HSC-T6) was stimulated with lipopolysaccharide (LPS) (100
      ng/ml). Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with
      Tan IIA (1, 3 and 10 uM), then induced by LPS (100 ng/ml). NF-kappaB activity was
      evaluated by the luciferase reporter gene assay. Western blotting analysis was
      performed to measure NF-kappaB-p65, and phosphorylations of MAPKs (ERK, JNK,
      p38). Cell chemotaxis was assessed by both wound-healing assay and trans-well
      invasion assay. Quantitative real-time PCR was used to detect gene expression in
      HSC-T6 cells. RESULTS: All concentrations of drugs showed no cytotoxicity against
      HSC-T6 cells. LPS stimulated NF-kappaB luciferase activities, nuclear
      translocation of NF-kappaB-p65, and phosphorylations of ERK, JNK and p38, all of
      which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited
      LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion
      assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3,
      CCL5, IL-1beta, TNF-alpha, IL-6, ICAM-1, iNOS, and alpha-SMA in HSC-T6 cells.
      CONCLUSION: Our results demonstrated that Tan IIA decreased LPS-induced HSC
      activation.

PMID- 25076489
TI  - The more we search, the more we find: discovery of a new lineage and a new
      species complex in the genus Asparagopsis.
AB  - In the past few decades, in the marine realm in particular, the use of molecular
      tools has led to the discovery of hidden taxonomic diversity, revealing complexes
      of sister species. A good example is the red algal genus Asparagopsis. The two
      species (A. armata and A. taxiformis) recognized in this genus have been
      introduced in many places around the world. Within the nominal species A.
      taxiformis, previous molecular analyses have uncovered several lineages,
      suggesting the existence of sister species or subspecies. Although the genus has
      been well studied in some regions (e.g., the Mediterranean Sea and Hawaii), it
      remains poorly investigated in others (e.g., South Pacific). Our study mainly
      focused on these latter areas to clarify lineages and better determine lineage
      status (i.e., native vs. introduced). A total of 188 specimens were collected
      from 61 sites, 58 of which had never been sampled before. We sequenced the DNA
      from samples for three markers and obtained 112 sequences for the chloroplastic
      RuBisCo spacer, 118 sequences for the nuclear LSU rRNA gene, and 174 for the
      mitochondrial spacer cox2-3. Phylogenetic analyses using all three markers
      suggested the existence of two cryptic sister species with the discovery of a new
      clade within A. armata. This clade was found only in Western Australia, Tasmania
      and New Zealand, and is thus restricted to a subregional biogeographic unit. We
      also discovered a new, fifth lineage for A. taxiformis restricted to the South
      Pacific and Western Australia. Except for this newly described lineage, all other
      lineages showed a global distribution influenced by introduction events. These
      results illustrate the difficulty in accurately defining cosmopolitan species.
      Our findings also highlight the need for targeted (i.e., in poorly studied areas)
      and geographically extensive sampling efforts when studying taxa that have been
      introduced globally and that are likely to hide species complexes. 

PMID- 25076490
TI  - Associations between cyberbullying and school bullying victimization and suicidal
      ideation, plans and attempts among Canadian schoolchildren.
AB  - PURPOSE: The negative effects of peer aggression on mental health are key issues
      for public health. The purpose of this study was to examine the associations
      between cyberbullying and school bullying victimization with suicidal ideation,
      plans and attempts among middle and high school students, and to test whether
      these relationships were mediated by reports of depression. METHODS: Data for
      this study are from the 2011 Eastern Ontario Youth Risk Behaviour Survey, which
      is a cross-sectional regional school-based survey that was conducted among
      students in selected Grade 7 to 12 classes (1658 girls, 1341 boys; mean +/- SD
      age: 14.3 +/- 1.8 years). RESULTS: Victims of cyberbullying and school bullying
      incurred a significantly higher risk of suicidal ideation (cyberbullying: crude
      odds ratio, 95% confidence interval  = 3.31, 2.16-5.07; school bullying: 3.48,
      2.48-4.89), plans (cyberbullying: 2.79, 1.63-4.77; school bullying: 2.76, 2.20
      3.45) and attempts (cyberbullying: 1.73, 1.26-2.38; school bullying: 1.64, 1.18
      2.27) compared to those who had not encountered such threats. Results were
      similar when adjusting for sociodemographic characteristics, substance use, and
      sedentary activities. Mediation analyses indicated that depression fully mediated
      the relationship between cyberbullying victimization and each of the outcomes of
      suicidal ideation, plans and attempts. Depression also fully mediated the
      relationship between school bullying victimization and suicide attempts, but
      partially mediated the relationship between school bullying victimization and
      both suicidal ideation and plans. CONCLUSION: These findings support an
      association between both cyberbullying and school bullying victimization and risk
      of suicidal ideation, plans and attempts. The mediating role of depression on
      these links justifies the need for addressing depression among victims of both
      forms of bullying to prevent the risk of subsequent suicidal behaviours.

PMID- 25076493
TI  - Can male circumcision have an impact on the HIV epidemic in men who have sex with
      men?
AB  - BACKGROUND: Three trials have demonstrated the prophylactic effect of male
      circumcision (MC) for HIV acquisition among heterosexuals, and MC interventions
      are underway throughout sub-Saharan Africa. Similar efforts for men who have sex
      with men (MSM) are stymied by the potential for circumcised MSM to acquire HIV
      easily through receptive sex and transmit easily through insertive sex. Existing
      work suggests that MC for MSM should reach its maximum potential in settings
      where sexual role segregation is historically high and relatively stable across
      the lifecourse; HIV incidence among MSM is high; reported willingness for
      prophylactic circumcision is high; and pre-existing circumcision rates are low.
      We aim to identify the likely public health impact that MC interventions among
      MSM would have in one setting that fulfills these conditions-Peru-as a
      theoretical upper bound for their effectiveness among MSM generally. METHODS AND
      FINDINGS: We use a dynamic, stochastic sexual network model based in exponential
      family random graph modeling and parameterized from multiple behavioral surveys
      of Peruvian MSM. We consider three enrollment criteria (insertive during 100%,
      >80% or >60% of UAI) and two levels of uptake (25% and 50% of eligible men); we
      explore sexual role proportions from two studies and different frequencies of
      switching among role categories. Each scenario is simulated 10 times. We estimate
      that efficiency could reach one case averted per 6 circumcisions. However, the
      population-level impact of an optimistic MSM-MC intervention in this setting
      would likely be at most ~5-10% incidence and prevalence reductions over 25 years.
      CONCLUSIONS: Roll-out of MC for MSM in Peru would not result in a substantial
      reduction in new HIV infections, despite characteristics in this population that
      could maximize such effects. Additional studies are needed to confirm these
      results for other MSM populations, and providers may consider the individual
      health benefits of offering MC to their MSM patients.

PMID- 25076492
TI  - Interferon regulatory factor-5 deficiency ameliorates disease severity in the
      MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2.
AB  - Interferon regulatory factor 5 (IRF5) polymorphisms are strongly associated with
      an increased risk of developing the autoimmune disease systemic lupus
      erythematosus. In mouse lupus models, IRF5-deficiency was shown to reduce disease
      severity consistent with an important role for IRF5 in disease pathogenesis.
      However these mouse studies were confounded by the recent demonstration that the
      IRF5 knockout mouse line contained a loss-of-function mutation in the dedicator
      of cytokinesis 2 (DOCK2) gene. As DOCK2 regulates lymphocyte trafficking and Toll
      like receptor signaling, this raised the possibility that some of the protective
      effects attributed to IRF5 deficiency in the mouse lupus models may instead have
      been due to DOCK2 deficiency. We have therefore here evaluated the effect of IRF5
      deficiency in the MRL/lpr mouse lupus model in the absence of the DOCK2 mutation.
      We find that IRF5-deficient (IRF5-/-) MRL/lpr mice develop much less severe
      disease than their IRF5-sufficient (IRF5+/+) littermates. Despite markedly lower
      serum levels of anti-nuclear autoantibodies and reduced total splenocyte and CD4+
      T cell numbers, IRF5-/- MRL/lpr mice have similar numbers of all splenic B cell
      subsets compared to IRF5+/+ MRL/lpr mice, suggesting that IRF5 is not involved in
      B cell development up to the mature B cell stage. However, IRF5-/- MRL/lpr mice
      have greatly reduced numbers of spleen plasmablasts and bone marrow plasma cells.
      Serum levels of B lymphocyte stimulator (BLyS) were markedly elevated in the
      MRL/lpr mice but no effect of IRF5 on serum BLyS levels was seen. Overall our
      data demonstrate that IRF5 contributes to disease pathogenesis in the MRL/lpr
      lupus model and that this is due, at least in part, to the role of IRF5 in plasma
      cell formation. Our data also suggest that combined therapy targeting both IRF5
      and BLyS might be a particularly effective therapeutic approach in lupus. 

PMID- 25076494
TI  - Evaluating the accuracy of molecular diagnostic testing for canine visceral
      leishmaniasis using latent class analysis.
AB  - Host tissues affected by Leishmania infantum have differing degrees of
      parasitism. Previously, the use of different biological tissues to detect L.
      infantum DNA in dogs has provided variable results. The present study was
      conducted to evaluate the accuracy of molecular diagnostic testing (qPCR) in dogs
      from an endemic area for canine visceral leishmaniasis (CVL) by determining which
      tissue type provided the highest rate of parasite DNA detection. Fifty-one
      symptomatic dogs were tested for CVL using serological, parasitological and
      molecular methods. Latent class analysis (LCA) was performed for accuracy
      evaluation of these methods. qPCR detected parasite DNA in 100% of these animals
      from at least one of the following tissues: splenic and bone marrow aspirates,
      lymph node and skin fragments, blood and conjunctival swabs. Using latent
      variable as gold standard, the qPCR achieved a sensitivity of 95.8% (CI 90.4-100)
      in splenic aspirate; 79.2% (CI 68-90.3) in lymph nodes; 77.3% (CI 64.5-90.1) in
      skin; 75% (CI 63.1-86.9) in blood; 50% (CI 30-70) in bone marrow; 37.5% (CI 24.2
      50.8) in left-eye; and 29.2% (CI 16.7-41.6) in right-eye conjunctival swabs. The
      accuracy of qPCR using splenic aspirates was further evaluated in a random larger
      sample (n = 800), collected from dogs during a prevalence study. The specificity
      achieved by qPCR was 76.7% (CI 73.7-79.6) for splenic aspirates obtained from the
      greater sample. The sensitivity accomplished by this technique was 95% (CI 93.5
      96.5) that was higher than those obtained for the other diagnostic tests and was
      similar to that observed in the smaller sampling study. This confirms that the
      splenic aspirate is the most effective type of tissue for detecting L. infantum
      infection. Additionally, we demonstrated that LCA could be used to generate a
      suitable gold standard for comparative CVL testing. 

PMID- 25076496
TI  - [CD-11 psychological disturbance treatment divisions: summary of the position of
      the World Psychiatric Association (WPA)].

PMID- 25076497
TI  - Learning to adapt.

PMID- 25076498
TI  - Knowledge, systems, teamwork keys to proper treatment decisions.

PMID- 25076495
TI  - Effect of tree nuts on glycemic control in diabetes: a systematic review and meta
      analysis of randomized controlled dietary trials.
AB  - BACKGROUND: Tree nut consumption has been associated with reduced diabetes risk,
      however, results from randomized trials on glycemic control have been
      inconsistent. OBJECTIVE: To provide better evidence for diabetes guidelines
      development, we conducted a systematic review and meta-analysis of randomized
      controlled trials to assess the effects of tree nuts on markers of glycemic
      control in individuals with diabetes. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and
      Cochrane databases through 6 April 2014. STUDY SELECTION: Randomized controlled
      trials >=3 weeks conducted in individuals with diabetes that compare the effect
      of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c,
      fasting glucose, fasting insulin, and HOMA-IR. DATA EXTRACTION AND SYNTHESIS: Two
      independent reviewer's extracted relevant data and assessed study quality and
      risk of bias. Data were pooled by the generic inverse variance method and
      expressed as mean differences (MD) with 95% CI's. Heterogeneity was assessed
      (Cochran Q-statistic) and quantified (I2). RESULTS: Twelve trials (n = 450) were
      included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly
      lowered HbA1c (MD = -0.07% [95% CI:-0.10, -0.03%]; P = 0.0003) and fasting
      glucose (MD = -0.15 mmol/L [95% CI: -0.27, -0.02 mmol/L]; P = 0.03) compared with
      control diets. No significant treatment effects were observed for fasting insulin
      and HOMA-IR, however the direction of effect favoured tree nuts. LIMITATIONS:
      Majority of trials were of short duration and poor quality. CONCLUSIONS: Pooled
      analyses show that tree nuts improve glycemic control in individuals with type 2
      diabetes, supporting their inclusion in a healthy diet. Owing to the
      uncertainties in our analyses there is a need for longer, higher quality trials
      with a focus on using nuts to displace high-glycemic index carbohydrates. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01630980.

PMID- 25076499
TI  - Universal adhesives: the evolution of adhesive solutions continues.

PMID- 25076500
TI  - DENTSPLY Caulk's Prime&Bond Elect(r): predictable bond strengths, without
      sensitivity.

PMID- 25076501
TI  - Ivoclar Vivadent's Adhese(r) Universal with VivaPen(r): effective delivery for
      all etching methods.

PMID- 25076502
TI  - Kerr's universal two-bottle OptiBondTM XTR allows consistent protocol for every
      procedure.

PMID- 25076504
TI  - Low shrinkage stress helps Shofu's BEAUTIFIL-Bulk materials deliver long-lasting
      results.

PMID- 25076503
TI  - An update on adhesive dentistry.

PMID- 25076505
TI  - Preface: Local and systemic effects of wear particles from orthopedic devices.

PMID- 25076506
TI  - The Brazilian dental science.

PMID- 25076507
TI  - An interview with Marissa C. Keesler.

PMID- 25076508
TI  - [Selected pages of history of vascular surgery in Russia (contribution of Russian
      surgeons to world vascular surgery)].
AB  - The article describes the most significant for Russian surgery personalities,
      facts, and events of the last 180years. An emphasis is placed upon those works,
      discoveries or operations made by Russians for the first timein the world's
      practice. To such we refer N.J. Pirogov's topographical anatomy of vessels
      (1837), N. V. Ekk's portocaval anastomosis (1877), A.A. Yanovsky's lateral
      arterial suture (1889), S.S. Bryukhonenko's artificial circulation unit (1923
      1924), Yu. Yu. Voronoy's renal replantation onto femoral vessels (1933), V.P.
      Demikhov'stransplantation of vital organs (1946-1959), V.I. Kolesov's mammary
      coronary anastomosis (1964),F.A. Serbinenko's endovascular neurosurgery ( 1979),
      E. I. Chasov's intracoronary thrombolysis by E.I. Chazov( 1974), endovascular
      prosthetic repair of the thoracic aorta by N.L. Volodos ( 1985) and a series of
      other facts.

PMID- 25076509
TI  - [Professor Iosif Khaimovich Rabkin and his priorities in roentgenoendovascular
      surgery].
AB  - The article is dedicated to outstanding Soviet and Russian interventional
      radiologist, Professor I. Kh. Rabkin and his priorities in the development of
      roentgenoendovascular methods of diagnosis and treatment of arterial and venous
      diseases. Virtually simultaneously with American surgeons, I. Kh. Rabkin not only
      worked out anew method of intravascular stenting of arteries with spirals made of
      shape-memory metal ( nitinol) but was the first in the world who in 1984
      successfully stented the external iliac artery in a 56-year-old male patient with
      stage IV limb ischaemia.

PMID- 25076510
TI  - [Academician V.A. Nasonova's role in the study of systemic vasculitides].
AB  - Article is dedicated to academician V.A.Nasonova contribution to the development
      of clinic, diagnostics and treatment of systemic vasculitides].

PMID- 25076511
TI  - [Review of materials of the Fourth European Venous Forum (Stockholm, Sweden)].
AB  - The article provides a brief review of the opinions and experience of the leading
      phlebologists from various countries, reflecting the latest updates and current
      problems regarding state-of-the-art management of diseases of major veins of
      lower extremities. Special attention is focussed on deep vein thromboses and
      consequence thereof, as well as varicose disease. This is followed by description
      of novel approaches to treatment of the pathology concerned.

PMID- 25076512
TI  - Characterization of fatigue states in medicine and psychiatry by structured
      interview.
AB  - CONTEXT: Unexplained fatigue states are prevalent, with uncertain diagnostic
      boundaries. OBJECTIVE: Patients with fatigue-related illnesses were investigated
      by questionnaire and a novel semistructured interview to identify discriminatory
      features. METHODS: Cross-sectional samples of women from specialist practices
      with chronic fatigue syndrome (n = 20), postcancer fatigue (PCF; n = 20), or
      major depression (n = 16) were recruited. Additionally, two longitudinal samples
      were studied: women with fatigue associated with acute infection who subsequently
      developed postinfective fatigue syndrome (n = 20) or recovered uneventfully (n =
      21), and women undergoing adjuvant therapy for breast cancer experiencing
      treatment-related fatigue who subsequently developed PCF (n = 16) or recovered
      uneventfully (n = 16). Patients completed self-report questionnaires, and trained
      interviewers applied the Semi-structured Clinical Interview for Neurasthenia. The
      receiver operating characteristics curves of the interview were measured against
      clinician-designated diagnoses. Cluster analyses were performed to empirically
      partition participants by symptom characteristics. RESULTS: The interview had
      good internal consistency (Cronbach alpha "fatigue" = .83), and diagnostic
      sensitivity and specificity for chronic fatigue syndrome (100% and 83%) and major
      depression (100% and 72%), with reasonable parameters for PCF (72% and 58%).
      Empirical clustering by "fatigue" or "neurocognitive difficulties" items
      allocated most patients to one group, whereas "mood disturbance" items correctly
      classified patients with depression only. CONCLUSIONS: The Semi-structured
      Clinical Interview for Neurasthenia offers reliable diagnostic use in assessing
      fatigue-related conditions. The symptom domains of fatigue and neurocognitive
      difficulties are shared across medical and psychiatric boundaries, whereas
      symptoms of depression such as anhedonia are distinguishing.

PMID- 25076513
TI  - Removal of total cyanide in coking wastewater during a coagulation process:
      significance of organic polymers.
AB  - Whether a cationic organic polymer can remove more total cyanide (TCN) than a non
      ionic organic polymer during the same flocculation system has not been reported
      previously. In this study, the effects of organic polymers with different charge
      density on the removal mechanisms of TCN in coking wastewater are investigated by
      polyferric sulfate (PFS) with a cationic organic polymer (PFS-C) or a non-ionic
      polymer (PFS-N). The coagulation experiments results show that residual
      concentrations of TCN (Fe(CN)6(3-)) after PFS-C flocculation (TCN < 0.2 mg/L) are
      much lower than that after PFS-N precipitation. This can be attributed to the
      different TCN removal mechanisms of the individual organic polymers. To
      investigate the roles of organic polymers, physical and structural
      characteristics of the flocs are analyzed by FT-IR, XPS, TEM and XRD. Owing to
      the presence of N+ in PFS-C, Fe(CN)6(3-) and negative flocs (Fe(CN)6(3-) adsorbed
      on ferric hydroxides) can be removed via charge neutralization and electrostatic
      patch flocculation by the cationic organic polymer. However, non-ionic N in PFS-N
      barely reacts with cyanides through sweeping or bridging, which indicates that
      the non-ionic polymer has little influence on TCN removal.

PMID- 25076514
TI  - Removal of arsenate with hydrous ferric oxide coprecipitation: effect of humic
      acid.
AB  - Insights from the adverse effect of humic acid (HA) on arsenate removal with
      hydrous ferric oxide (HFO) coprecipitation can further our understanding of the
      fate of As(V) in water treatment process. The motivation of our study is to
      explore the competitive adsorption mechanisms of humic acid and As(V) on HFO on
      the molecular scale. Multiple complementary techniques were used including
      macroscopic adsorption experiments, surface enhanced Raman scattering (SERS),
      extended X-ray absorption fine structure (EXAFS) spectroscopy, flow-cell
      attenuated total reflectance Fourier transform infrared (ATR-FTIR) measurement,
      and charge distribution multisite complexation (CD-MUSIC) modeling. The As(V)
      removal efficiency was reduced from over 95% to about 10% with the increasing HA
      concentration to 25 times of As(V) mass concentration. The SERS analysis excluded
      the HA-As(V) complex formation. The EXAFS results indicate that As(V) formed
      bidentate binuclear surface complexes in the presence of HA as evidenced by an As
      Fe distance of 3.26-3.31 angstroms. The in situ ATR-FTIR measurements show that
      As(V) replaces surface hydroxyl groups and forms innersphere complex. High
      concentrations of HA may physically block the surface sites and inhibit the As(V)
      access. The adsorption of As(V) and HA decreased the point of zero charge of HFO
      from 7.8 to 5.8 and 6.3, respectively. The CD-MUSIC model described the zeta
      potential curves and adsorption edges of As(V) and HA reasonably well.

PMID- 25076515
TI  - Arsenic removal from groundwater by acclimated sludge under autohydrogenotrophic
      conditions.
AB  - Arsenic in the environment is attracting increasing attention due to its chronic
      health effects. Although arsenite (As(III)) is generally more mobile and more
      toxic than arsenate (As(V)), reducing As(V) to As(III) may still be a means for
      decontamination, because As(III) can be removed from solution by precipitation
      with sulfide or by adsorption or complexation with other metal sulfides. The
      performance of As(V) bio-reduction under autohydrogenotrophic conditions was
      investigated with batch experiments. The results showed that As(V) reduction was
      a biochemical process while both acclimated sludge and hydrogen were essential.
      Most of the reduced arsenic remained in a soluble form, although 20% was removed
      with no addition of sulfate, while 82% was removed when sulfate was reduced to
      sulfide. The results demonstrated that the reduced arsenic was re-sequestered in
      the precipitates, probably as arsenic sulfides. Kinetic analysis showed that
      pseudo first-order kinetics described the bio-reduction process better than
      pseudo second-order. In particular, the influences of pH and temperature on As(V)
      reduction by acclimated sludge under autohydrogenotrophic conditions and total
      soluble As removal were examined. The reduction process was highly sensitive to
      both pH and temperature, with the optimum ranges of pH 6.5-7.0 and 30-40 degrees
      C respectively. Furthermore, Arrhenius modeling results for the temperature
      effect indicated that the As(V) reduction trend was systematic. Total soluble As
      removal was consistent with the trend of As(V) reduction.

PMID- 25076516
TI  - Characteristics of greenhouse gas emission in three full-scale wastewater
      treatment processes.
AB  - Three full-scale wastewater treatment processes, Orbal oxidation ditch,
      anoxic/anaerobic/aerobic (reversed A2O) and anaerobic/anoxic/aerobic (A2O), were
      selected to investigate the emission characteristics of greenhouse gases (GHG),
      including carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O). Results
      showed that although the processes were different, the units presenting high GHG
      emission fluxes were remarkably similar, namely the highest CO2 and N2O emission
      fluxes occurred in the aerobic areas, and the highest CH4 emission fluxes
      occurred in the grit tanks. The GHG emission amount of each unit can be
      calculated from its area and GHG emission flux. The calculation results revealed
      that the maximum emission amounts of CO2, CH4 and N2O in the three wastewater
      treatment processes appeared in the aerobic areas in all cases. Theoretically,
      CH4 should be produced in anaerobic conditions, rather than aerobic conditions.
      However, results in this study showed that the CH4 emission fluxes in the
      forepart of the aerobic area were distinctly higher than in the anaerobic area.
      The situation for N2O was similar to that of CH4: the N2O emission flux in the
      aerobic area was also higher than that in the anoxic area. Through analysis of
      the GHG mass balance, it was found that the flow of dissolved GHG in the
      wastewater treatment processes and aerators may be the main reason for this
      phenomenon. Based on the monitoring and calculation results, GHG emission factors
      for the three wastewater treatment processes were determined. The A2O process had
      the highest CO2 emission factor of 319.3 g CO2/kg COD(removed), and the highest
      CH4 and N2O emission factors of 3.3 g CH4/kg COD(removed) and 3.6 g N2O/kg
      TN(removed) were observed in the Orbal oxidation ditch process.

PMID- 25076517
TI  - Effect of temperature on anoxic metabolism of nitrites to nitrous oxide by
      polyphosphate accumulating organisms.
AB  - Temperature is an important physical factor, which strongly influences biomass
      and metabolic activity. In this study, the effects of temperature on the anoxic
      metabolism of nitrite (NO2(-)) to nitrous oxide (N2O) by polyphosphate
      accumulating organisms, and the process of the accumulation of N2O (during
      nitrite reduction), which acts as an electron acceptor, were investigated using
      91% +/- 4% Candidatus Accumulibacter phosphatis sludge. The results showed that
      N2O is accumulated when Accumulibacter first utilize nitrite instead of oxygen as
      the sole electron acceptor during the denitrifying phosphorus removal process.
      Properties such as nitrite reduction rate, phosphorus uptake rate, N2O reduction
      rate, and polyhydroxyalkanoate degradation rate were all influenced by
      temperature variation (over the range from 10 to 30 degrees C reaching maximum
      values at 25 degrees C). The reduction rate of N2O by N2O reductase was more
      sensitive to temperature when N2O was utilized as the sole electron acceptor
      instead of N2O, and the N2O reduction rates, ranging from 0.48 to 3.53 N20-N/(hr
      x g VSS), increased to 1.45 to 8.60 mg N2O-N/(hr x g VSS). The kinetics processes
      for temperature variation of 10 to 30 degrees C were (theta1 = 1.140-1.216 and
      theta2 = 1.139-1.167). In the range of 10 degrees C to 30 degrees C, almost all
      of the anoxic stoichiometry was sensitive to temperature changes. In addition, a
      rise in N2O reduction activity leading to a decrease in N2O accumulation in long
      term operations at the optimal temperature (27 degrees C calculated by the
      Arrhenius model).

PMID- 25076518
TI  - Efficacy of two chemical coagulants and three different filtration media on
      removal of Aspergillus flavus from surface water.
AB  - Aquatic fungi are common in various aqueous environments and play potentially
      crucial roles in nutrient and carbon cycling as well as interacting with other
      organisms. Species of Aspergillus are the most common fungi that occur in water.
      The present study was undertaken to elucidate the efficacy of two coagulants,
      aluminum sulfate and ferric chloride, used at different concentrations to treat
      drinking water, in removing Aspergillus flavus, as well as testing three
      different filtration media: sand, activated carbon, and ceramic granules, for
      their removal of fungi from water. The results revealed that both coagulants were
      effective in removing fungi and decreasing the turbidity of drinking water, and
      turbidity decreased with increasing coagulant concentration. Also, at the highest
      concentration of the coagulants, A. flavus was decreased by 99.6% in the treated
      water. Among ceramic granules, activated carbon, and sand used as media for water
      filtration, the sand and activated carbon filters were more effective in removing
      A. flavus than ceramic granules while simultaneously decreasing the turbidity
      levels in the test water samples. Post-treatment total organic carbon (TOC) and
      total nitrogen (TN) concentrations in the experimental water did not decrease; on
      the contrary, TN concentrations increased with the increasing dosage of
      coagulants. The filtration process had no effect in reducing TOC and TN in tested
      water.

PMID- 25076519
TI  - Beyond hypoxia: occurrence and characteristics of black blooms due to the
      decomposition of the submerged plant Potamogeton crispus in a shallow lake.
AB  - Organic matter-induced black blooms (hypoxia and an offensive odor) are a serious
      ecosystem disasters that have occurred in some large eutrophic shallow lakes in
      China. In this study, we investigated two separate black blooms that were induced
      by Potamogeton crispus in Lake Taihu, China. The main physical and chemical
      characteristics, including color- and odor-related substances, of the black
      blooms were analyzed. The black blooms were characterized by low dissolved oxygen
      concentration (close to 0 mg/L), low oxidation-reduction potential, and
      relatively low pH of overlying water. Notably higher Fe2+ and sigmaS(2-) were
      found in the black-bloom waters than in waters not affected by black blooms. The
      black color of the water may be attributable to the high concentration of these
      elements, as black FeS was considered to be the main substance causing the black
      color of blooms in freshwater lakes. Volatile organic sulfur compounds, including
      dimethyl sulfide, dimethyl disulfide, and dimethyl trisulfide, were very abundant
      in the black-bloom waters. The massive anoxic degradation of dead Potamogeton
      crispus plants released dimethyl sulfide, dimethyl disulfide, and dimethyl
      trisulfide, which were the main odor-causing compounds in the black blooms. The
      black blooms also induced an increase in ammonium nitrogen and soluble reactive
      phosphorus levels in the overlying waters. This extreme phenomenon not only
      heavily influenced the original lake ecosystem but also greatly changed the
      cycling of Fe, S, and nutrients in the water column.

PMID- 25076520
TI  - Spatial and temporal variations of two cyanobacteria in the mesotrophic Miyun
      reservoir, China.
AB  - Spatial variations in phytoplankton community within a large mesotrophic
      reservoir (Miyun reservoir, North China) were investigated in relation to
      variations in physico-chemical properties, nutrient concentrations, temperature
      and light conditions over a 5 month period in 2009. The dynamics of phytoplankton
      community was represented by the dominance of cyanobacteria through summer and
      fall, following with a short-term dominance of chlorophyta in late fall, and a
      relatively high abundance of diatom in October; on the other hand, maximum
      phytoplankton biomass was recorded in the north shallow region of Miyun reservoir
      with a higher nutrients level. Particular attention was paid to the impacts of
      environmental conditions on the growth of two cyanobacteria genera, the toxin
      producing Microcystis and the taste & odor-producing Oscillatoria. Microcystis
      biomass was in general greatly affected by water temperature and mixing
      depth/local water depth ratio in this reservoir, while the Oscillatoria biomass
      in the surface and middle layers was greatly affected by total dissolved
      phosphorus, and that in the bottom layer was related with the Secchi depth/local
      water depth ratio. Abundant Oscillatoria biomass was observed only in late
      September when Microcystis biomass decreased and allowed sufficient light go
      through.

PMID- 25076521
TI  - Quantification of viable bacteria in wastewater treatment plants by using
      propidium monoazide combined with quantitative PCR (PMA-qPCR).
AB  - The detection of viable bacteria in wastewater treatment plants (WWTPs) is very
      important for public health, as WWTPs are a medium with a high potential for
      waterborne disease transmission. The aim of this study was to use propidium
      monoazide (PMA) combined with the quantitative polymerase chain reaction (PMA
      qPCR) to selectively detect and quantify viable bacteria cells in full-scale
      WWTPs in China. PMA was added to the concentrated WWTP samples at a final
      concentration of 100 micromol/L and the samples were incubated in the dark for 5
      min, and then lighted for 4 min prior to DNA extraction and qPCR with specific
      primers for Escherichia coli and Enterococci, respectively. The results showed
      that PMA treatment removed more than 99% of DNA from non-viable cells in all the
      WWTP samples, while matrices in sludge samples markedly reduced the effectiveness
      of PMA treatment. Compared to qPCR, PMA-qPCR results were similar and highly
      linearly correlated to those obtained by culture assay, indicating that DNA from
      non-viable cells present in WWTP samples can be eliminated by PMA treatment, and
      that PMA-qPCR is a reliable method for detection of viable bacteria in
      environmental samples. This study demonstrated that PMA-qPCR is a rapid and
      selective detection method for viable bacteria in WWTP samples, and that WWTPs
      have an obvious function in removing both viable and non-viable bacteria. The
      results proved that PMA-qPCR is a promising detection method that has a high
      potential for application as a complementary method to the standard culture-based
      method in the future.

PMID- 25076522
TI  - Antimony(V) removal from water by hydrated ferric oxides supported by calcite
      sand and polymeric anion exchanger.
AB  - We fabricated and characterized two hybrid adsorbents originated from hydrated
      ferric oxides (HFOs) using a polymeric anion exchanger D201 and calcite as host.
      The resultant adsorbents (denoted as HFO-201 and IOCCS) were employed for Sb(V)
      removal from water. Increasing solution pH from 3 to 9 apparently weakened Sb(V)
      removal by both composites, while increasing temperature from 293 to 313 K only
      improved Sb(V) uptake by IOCCS. HFO-201 exhibited much higher capacity for Sb(V)
      than for IOCCS in the absence of other anions in solution. Increasing ionic
      strength from 0.01 to 0.1 mol/L NaNO3 would result in a significant drop of the
      capacity of HFO-201 in the studied pH ranges; however, negligible effect was
      observed for IOCCS under similar conditions. Similarly, the competing chloride
      and sulfate pose more negative effect on Sb(V) adsorption by HFO-201 than by
      IOCCS, and the presence of silicate greatly decreased their adsorption
      simultaneously, while calcium ions were found to promote the adsorption of both
      adsorbents. XPS analysis further demonstrated that preferable Sb(V) adsorption by
      both hybrids was attributed to the inner sphere complexation of Sb(V) and HFO,
      and Ca(II) induced adsorption enhancement possibly resulted from the formation of
      HFO-Ca-Sb complexes. Column adsorption runs proved that Sb(V) in the synthetic
      water could be effectively removed from 30 microg/L to below 5 microg/L (the
      drinking water standard regulated by China), and the effective treatable volume
      of IOCCS was around 6 times as that of HFO-201, implying that HFO coatings onto
      calcite might be a more effective approach than immobilization inside D201.

PMID- 25076523
TI  - Biostability in distribution systems in one city in southern China:
      characteristics, modeling and control strategy.
AB  - This study investigated the bacterial regrowth in drinking water distribution
      systems receiving finished water from an advanced drinking water treatment plant
      in one city in southern China. Thirteen nodes in two water supply zones with
      different aged pipelines were selected to monitor water temperature, dissolved
      oxygen (DO), chloramine residual, assimilable organic carbon (AOC), and
      heterotrophic plate counts (HPC). Regression and principal component analyses
      indicated that HPC had a strong correlation with chloramine residual. Based on
      Chick-Watson's Law and the Monod equation, biostability curves under different
      conditions were developed to achieve the goal of HPC < or = 100 CFU/mL. The
      biostability curves could interpret the scenario under various AOC concentrations
      and predict the required chloramine residual concentration under the condition of
      high AOC level. The simulation was also carried out to predict the scenario with
      a stricter HPC goal (< or = 50 CFU/mL) and determine the required chloramine
      residual. The biological regrowth control strategy was assessed using
      biostability curve analysis. The results indicated that maintaining high
      chloramine residual concentration was the most practical way to achieve the goal
      of HPC < or = 100 CFU/mL. Biostability curves could be a very useful tool for
      biostability control in distribution systems. This work could provide some new
      insights towards biostability control in real distribution systems.

PMID- 25076524
TI  - Characteristics of ozone and ozone precursors (VOCs and NOx) around a petroleum
      refinery in Beijing, China.
AB  - A field measurement campaign for ozone and ozone precursors (VOCs and NOx) was
      conducted in summer 2011 around a petroleum refinery in the Beijing rural region.
      Three observation sites were arranged, one at southwest of the refinery as the
      background, and two at northeast of the refinery as the downwind receptors.
      Monitoring data revealed the presence of serious surface O3 pollution with the
      characteristics of high average daily mean and maximum concentrations (64.0 and
      145.4 ppbV in no-rain days, respectively) and multi-peak diurnal variation. For
      NOx, the average hourly concentrations of NO2 and NO were in the range of 20.5
      46.1 and 1.8-6.4 ppbV, respectively. For VOC measurement, a total of 51 compounds
      were detected. Normally, TVOCs at the background site was only dozens of ppbC,
      while TVOCs at the downwind sites reached several hundreds of ppbC. By
      subtracting the VOC concentrations at background, chemical profiles of VOC
      emission from the refinery were obtained, mainly including alkanes (60.0% +/-
      4.3%), alkenes (21.1% +/- 5.5%) and aromatics (18.9% +/- 3.9%). Moreover, some
      differences in chemical profiles for the same measurement hours were observed
      between the downwind sites; the volume ratios of alkanes with low reactivity and
      those of alkenes with high reactivity respectively showed an increasing trend and
      a decreasing trend. Finally, based on temporal and spatial variations of VOC
      mixing ratios, their photochemical degradations and dispersion degradations were
      estimated to be 0.15-0.27 and 0.42-0.62, respectively, by the photochemical age
      calculation method, indicating stronger photochemical reactions around the
      refinery.

PMID- 25076525
TI  - Identification of sources of lead in the atmosphere by chemical speciation using
      X-ray absorption near-edge structure (XANES) spectroscopy.
AB  - Sources of Pb pollution in the local atmosphere together with Pb species, major
      ions, and heavy metal concentrations in a size-fractionated aerosol sample from
      Higashi-Hiroshima (Japan) have been determined by X-ray absorption near-edge
      structure (XANES) spectroscopy, ion chromatography, and ICP-MS/AES, respectively.
      About 80% of total Pb was concentrated in fine aerosol particles. Lead species in
      the coarse aerosol particles were PbC2O4, 2PbCO3 Pb(OH)2, and Pb(NO3)2, whereas
      Pb species in the fine aerosol particles were PbC2O4, PbSO4, and Pb(NO3)2.
      Chemical speciation and abundance data suggested that the source of Pb in the
      fine aerosol particles was different from that of the coarse ones. The dominant
      sources of Pb in the fine aerosol particles were judged to be fly ash from a
      municipal solid waste incinerator and heavy oil combustion. For the coarse
      aerosol particles, road dust was considered to be the main Pb source. In addition
      to Pb species, elemental concentrations in the aerosols were also determined. The
      results suggested that Pb species in size-fractionated aerosols can be used to
      identify the origin of aerosol particles in the atmosphere as an alternative to
      Pb isotope ratio measurement.

PMID- 25076526
TI  - Online monitoring of water-soluble ionic composition of PM10 during early summer
      over Lanzhou City.
AB  - Lanzhou is one of the most aerosol-polluted cities in China. In this study, an
      online analyzer for Monitoring for AeRosols and GAses was deployed to measure
      major water-soluble inorganic ions in PM10 at 1-hour time resolution, and 923
      samples were obtained from Apr 1 to May 24, 2011. During the field campaign, air
      pollution days were encountered with Air Quality Index more than 100 and daily
      average concentration of PM10 exceeding 150 microg/m3. Based on the variation of
      water-soluble ions and results of Positive Matrix Factorization 3.0 model
      execution, the air pollution days were classified as crustal species- or
      secondary aerosol-induced, and the different formation mechanisms of these two
      air pollution types were studied. During the crustal species pollution days, the
      content of Ca2+ increased and was about 2.3 times higher than the average on
      clear days, and the air parcel back trajectory was used to analyze the sources of
      crustal species. Data on sulfate, trace gases and meteorological factors were
      used to reveal the formation mechanism of secondary aerosol pollution. The sulfur
      oxidation ratio (SOR) was derived from the 923 samples, and the SOR had high
      positive correlation with relative humidity in early summer in Lanzhou.

PMID- 25076527
TI  - Effect of traffic restriction on atmospheric particle concentrations and their
      size distributions in urban Lanzhou, Northwestern China.
AB  - During the 2012 Lanzhou International Marathon, the local government made a
      significant effort to improve traffic conditions and air quality by implementing
      traffic restriction measures. To evaluate the direct effect of these measures on
      urban air quality, especially particle concentrations and their size
      distributions, atmospheric particle size distributions (0.5-20 microm) obtained
      using an aerodynamic particle sizer (model 3321, TSI, USA) in June 2012 were
      analyzed. It was found that the particle number, surface area and volume
      concentrations for size range 0.5-10 microm were (15.0 +/- 2.1) cm(-3), (11.8 +/-
      2.6) microm2/cm3 and (1.9 +/- 0.6) microm2/cm3, respectively, on the traffic
      restricted day (Sunday), which is 63.2%, 53.0% and 47.2% lower than those on a
      normal Sunday. For number and surface area concentrations, the most affected size
      range was 0.5-0.7 and 0.5-0.8 microm, respectively, while for volume
      concentration, the most affected size ranges were 0.5-0.8, 1.7-2.0 and 5.0-5.4
      microm. Number and volume concentrations of particles in size range 0.5-1.0
      microm correlated well with the number of non-CNG (Compressed Natural Gas)
      powered vehicles, while their correlation with the number of CNG-powered vehicles
      was very low, suggesting that reasonable urban traffic controls along with
      vehicle technology improvements could play an important role in improving urban
      air quality.

PMID- 25076528
TI  - A review on completing arsenic biogeochemical cycle: microbial volatilization of
      arsines in environment.
AB  - Arsenic (As) is ubiquitous in the environment in the carcinogenic inorganic
      forms, posing risks to human health in many parts of the world. Many
      microorganisms have evolved a series of mechanisms to cope with inorganic arsenic
      in their growth media such as transforming As compounds into volatile
      derivatives. Bio-volatilization of As has been suggested to play an important
      role in global As biogeochemical cycling, and can also be explored as a potential
      method for arsenic bioremediation. This review aims to provide an overview of the
      quality and quantity of As volatilization by fungi, bacteria, microalga and
      protozoans. Arsenic bio-volatilization is influenced by both biotic and abiotic
      factors that can be manipulated/elucidated for the purpose of As bioremediation.
      Since As bio-volatilization is a resurgent topic for both biogeochemistry and
      environmental health, our review serves as a concept paper for future research
      directions.

PMID- 25076529
TI  - Alginate modifies the physiological impact of CeO2 nanoparticles in corn
      seedlings cultivated in soil.
AB  - Alginates are naturally occurring components of organic matter in natural soil
      whose effects on nanoparticle (NP) toxicity to plants is not well understood. In
      the present study, corn plants were grown for one month in soil spiked with 400
      mg/kg CeO2 NPs with various alginate concentrations. After one month of growth in
      the NPs impacted soil, plants were harvested and analyzed for Ce and mineral
      element concentrations. Chlorophyll concentration and heat shock protein 70, used
      as biomarkers for oxidative stress, were also evaluated. Results showed that,
      compared to CeO2 NPs treatment, alginate at 10, 50, and 100 mg/kg increased Ce
      concentration in roots by approximately 46%, 38%, and 29% and by 115%, 45%, and
      56% in shoots, respectively. CeO2 NPs without alginate increased Mn accumulation
      in roots by 34% compared to control. CeO2 NPs with low and medium alginate
      increased Mn by ca. 92% respect to NPs without alginate and by ca. 155% respect
      to control. CeO2 NPs without/with alginate significantly increased accumulation
      of Fe and Al in roots. In addition, alginate at 50 mg/kg increased Zn
      accumulation in roots by 52% compared to control. In shoots, K increased at all
      NP treatments but the accumulation of other elements was not affected. Alginate
      enlarged the impact of CeO2 NPs to corn plants by reducing chlorophyll a content
      and triggering overexpression of heat shock protein 70.

PMID- 25076530
TI  - Humification characterization of biochar and its potential as a composting
      amendment.
AB  - Biochar has received increasing attention due to its applications as a soil
      amendment. Here, the chemical properties of solid and water-extractable fractions
      of four biochar samples were investigated. The results showed that wood biochar
      and bamboo biochar samples were 60%-80% more hydrophobic than those of rice husk
      biochar and rice husk ash. In addition, the acidity was 3.88 mmol/g from the
      total functional groups and 1.03 mmol/g from the carboxyl groups/lactones/phenols
      found in the wood biochar sample, which were about 1.5 times greater than those
      of the bamboo biochar sample. These functional groups could be used to determine
      the sorptive capacity of biochar for ionic solutes and water content and to
      increase the degradation of compost organics. The wood biochar sample was found
      to have the most humification materials (fulvic acid-like material + humic acid
      like material) in the water-extractable fraction, which was 3-10 times higher
      than that in the rice husk biochar and rice husk ash; humified materials were not
      detected in the bamboo biochar sample. Humification materials in biochar may be
      involved in increasing the proportion of humic acid-like materials in humic-like
      substances within the compost product. Wood biochar had better hydrophobic,
      sorptive, aromatic, and humification properties compared to other biochars,
      suggesting that it may be used in composting in order to exert its effect as both
      a bulking agent and a composting amendment during the solid waste composting
      process.

PMID- 25076531
TI  - Immigrant Pantoea agglomerans embedded within indigenous microbial aggregates: a
      novel spatial distribution of epiphytic bacteria.
AB  - Immigrant bacteria located on leaf surfaces are important to the health of plants
      as well as to people who consume fresh fruits and vegetables. However, the
      spatial distribution and organization of these immigrant bacteria on leaf
      surfaces are still poorly understood. To examine the spatial organization of
      these strains, two bacterial strains on tobacco leaves: (1) an indigenous strain,
      Pseudomonas stutzeri Nov. Y2011 labeled with green fluorescent protein, and (2)
      an immigrant strain Pantoea agglomerans labeled with cyan fluorescent protein
      isolated from pear, were studied. Under moist conditions, P. agglomerans cells
      quickly disappeared from direct observation by laser-scanning confocal
      microscopy, although elution results indicated that large amounts of live cells
      were still present on the leaves. Following exposure to desiccation stress,
      particles of cyan fluorescent protein-labeled P. agglomerans were visible within
      cracked aggregates of P. stutzeri Nov. Y2011. Detailed observation of sectioned
      aggregates showed that colonies of immigrant P. agglomerans were embedded within
      aggregates of P. stutzeri Nov. Y2011. Furthermore, carbon-resource partitioning
      studies suggested that these two species could coexist without significant
      nutritional competition. This is the first observation of an immigrant bacterium
      embedding within aggregates of indigenous bacteria on leaves to evade harsh
      conditions in the phyllosphere.

PMID- 25076532
TI  - Remediation of nutrient-rich waters using the terrestrial plant, Pandanus
      amaryllifolius Roxb.
AB  - Effective control of eutrophication is generally established through the
      reduction of nutrient loading into waterways and water bodies. An economically
      viable and ecologically sustainable approach to nutrient pollution control could
      involve the integration of retention ponds, wetlands and greenways into water
      management systems. Plants not only play an invaluable role in the assimilation
      and removal of nutrients, but they also support fauna richness and can be
      aesthetically pleasing. Pandanus amaryllifolius, a tropical terrestrial plant,
      was found to establish well in hydrophytic conditions and was highly effective in
      remediating high nutrient levels in an aquatic environment showing 100% removal
      of NO3(-)-N up to 200 mg/L in 14 days. Phosphate uptake by the plant was less
      efficient with 64% of the PO4(-)-P removed at the maximum concentration of 100
      mg/L at the end of 6 weeks. With its high NO3(-)-N and PO4(3-)-P removal
      efficiency, P. amaryllifolius depleted the nutrient-rich media and markedly
      contained the natural colonization of algae. The impediment of algal growth led
      to improvements in the water quality with significant decreases in turbidity, pH
      and electrical conductivity. In addition, the plants did not show stress symptoms
      when grown in high nutrient levels as shown by the changes in their biomass,
      total soluble proteins and chlorophyll accumulation as well as photochemical
      efficiency. Thus, P. amaryllifolius is a potential candidate for the mitigation
      of nutrient pollution in phytoremediation systems in the tropics as the plant
      requires low maintenance, is tolerant to the natural variability of weather
      conditions and fluctuating hydro-periods, and exhibit good nutrient removal
      capabilities.

PMID- 25076533
TI  - Construction of a dual fluorescence whole-cell biosensor to detect N-acyl
      homoserine lactones.
AB  - Detection of N-acyl homoserine lactones (AHLs) is useful for understanding quorum
      sensing (QS) behaviors, including biofilm formation, virulence and metabolism.
      For detecting AHLs and indicating the host cells in situ, we constructed the
      plasmid pUCGMA2T(1-4) to make a dual fluorescent whole-cell biosensor based on
      the AhlIR AHL system of Pseudomonas syringae pv. syringae B728a. The plasmid
      contains three components: constitutively expressed P(npatII::gfp) for indicating
      host cells, P(ahlI::mcherry) that produces red fluorescence in response to AHL,
      and the ahlR gene that encodes an AHL regulatory protein. Meanwhile, two copies
      of T(1-4) (four tandem copies of a transcriptional terminator) were added into
      the plasmid to reduce background. The results showed that when the plasmid was
      placed into Escherichia coli, the dual fluorescence whole-cell biosensor was able
      to respond with red fluorescence within 6 hr to 5 x 10(-8)-1 x 10(-5) mol/L of
      3OC6-HSL. Bright green fluorescence indicated the host cells. Furthermore, when
      the plasmid was transferred to wildtype Pseudomonas PhTA125 (an AHL-producing
      bacterium), it also showed both green and red fluorescence. This result
      demonstrates that this plasmid can be used to construct whole-cell indicators
      that can indicate the AHL response and spatial behaviors of microbes in a
      microenvironmental niche.

PMID- 25076534
TI  - Digestion performance and microbial community in full-scale methane fermentation
      of stillage from sweet potato-shochu production.
AB  - Sweet potato shochu is a traditional Japanese spirit produced mainly in the South
      Kyushu area in Japan. The amount of stillage reaches approximately 8 x 10(5) tons
      per year. Wastewater mainly containing stillage from the production of sweet
      potato-shochu was treated thermophilically in a full-scale treatment plant using
      fixed-bed reactors (8 reactors x 283 m3). Following the addition of Ni2+ and
      Co2+, the reactors have been stably operated for six years at a high chemical
      oxygen demand (COD) loading rate of 14 kg/(m3 x day). Analysis of coenzyme
      content and microbial communities indicated that similar microbial communities
      were present in the liquid phase and on the fiber carriers installed in reactors.
      Bacteria in the phyla Firmicutes as well as Bacteroidetes were dominant bacteria,
      and Methanosarcina thermophila as well as Methanothermobacter crinale were
      dominant methanogens in the reactors. This study reveals that stillage from sweet
      potato-shochu production can be treated effectively in a full-scale fixed-bed
      reactor under thermophilic conditions with the help of Ni2+ and Co2+. The high
      diversity of bacterial community and the coexistence of both aceticlastic and
      hydrogenotrophic methanogens contributed to the excellent fermentation
      performance.

PMID- 25076535
TI  - Health risk assessment of dietary exposure to polycyclic aromatic hydrocarbons in
      Taiyuan, China.
AB  - Sixteen polycyclic aromatic hydrocarbons (PAHs) were determined in 24 duplicate
      diet samples from people in Taiyuan during summer and winter in 2009. Dietary
      intake of PAHs for 2862 participants was subsequently estimated by a survey in
      Taiyuan. Results from these 24 samples were compared with a raw food study in
      Taiyuan in 2008. Three main sources of dietary PAHs are vegetables, wheat flour
      and fruits, the sum of which contributes 75.95% of PAHs in dietary food. Compared
      to the estimated value in raw food, much more B[a]P(eq) (benzo[a]pyrene
      equivalents) were detected in food samples collected in the duplicate-diet study
      in Taiyuan (60.75 ng/day). The cooking process may introduce more B[a]P(eq) into
      food, and the relative contribution of 16 PAHs in the diet would be changed
      during the cooking procedure.

PMID- 25076536
TI  - Acute toxicity formation potential of benzophenone-type UV filters in
      chlorination disinfection process.
AB  - Benzophenones (BPs) are a class of widely used UV filters, which have been
      frequently detected within multiple environmental matrices. Disinfection is a
      necessary process in water treatment processes. The transformation behaviors and
      toxicity changes of 14 BP-type UV filters during chlorination disinfection
      treatment were investigated in this study. A new index, the acute toxicity
      formation potential, was proposed to evaluate the toxicity changes and potential
      risks of BP-type UV filters during chlorination treatment. It was found that 13
      of 14 BP-type UV filters exhibited toxicity decreases in the chlorination
      disinfection process, more or less, while one showed a toxicity increase. The
      toxicity changes were dependent on substitution effects, such that 2,4-di
      hydroxylated or 3-hydroxylated BPs exhibited significant toxicity decreases after
      chlorination treatment due to the ready cleavage of the aromatic ring.
      Importantly, the acute toxicity changes could be duplicated in an ambient water
      matrix.

PMID- 25076537
TI  - Exposure measurement, risk assessment and source identification for exposure of
      traffic assistants to particle-bound PAHs in Tianjin, China.
AB  - To investigate the levels of exposure to particulate-bound polycyclic aromatic
      hydrocarbon (PAH) and to estimate the risk these levels pose to traffic
      assistants (TAs) in Tianjin (a megacity in North China), a measurement campaign
      (33 all-day exposure samples, 25 occupational-exposure samples and 10 indoor
      samples) was conducted to characterize the TAs' exposure to PAHs, assess the
      cancer risk and identify the potential sources of exposure. The average total
      exposure concentration of 14 PAHs was approximately 2871 +/- 928 ng/m3 (on-duty),
      and 1622 +/- 457 ng/m3 (all-day). The indoor PAHs level was 1257 +/- 107 ng/m3.
      After 8000 Monte Carlo simulations, the cancer risk resulting from exposure to
      PAHs was found to be approximately 1.05 x 10(-4). A multivariate analysis was
      applied to identify the potential sources, and the results showed that, in
      addition to vehicle exhaust, coal combustion and cooking fumes were also another
      two important contributors to personal PAH exposure. The diagnostic ratios of PAH
      compounds agree with the source apportionment results derived from principal
      component analysis.

PMID- 25076538
TI  - Fabrication of Bi2O3/TiO2 nanocomposites and their applications to the
      degradation of pollutants in air and water under visible-light.
AB  - A nanoheterojunction composite photocatalyst Bi2O3/TiO2 working under visible
      light (lambda > or = 420 nm) was prepared by combining two semiconductors Bi2O3
      and TiO2 varying the Bi2O3/TiO2 molar ratio. Maleic acid was employed as an
      organic binder to unite Bi2O3 and TiO2 nanoparticles. The SEM, TEM, XRD and
      diffuse reflectance spectra were utilized to characterize the prepared Bi2O3/TiO2
      nanoheterojunction. The nanocomposite exhibited unusual high photocatalytic
      activity in decomposing 2-propanol in gas phase and phenol in aqueous phase and,
      evolution of CO2 under visible light irradiation while the end members exhibited
      low photocatalytic activity. The composite was optimized to 5 mol% Bi2O3/TiO2.
      The remarkable high photocatalytic efficiency originates from the unique relative
      energy band position of Bi2O3 and TiO2 as well as the absorption of visible light
      by Bi2O3.

PMID- 25076539
TI  - Comparison of quartz sand, anthracite, shale and biological ceramsite for
      adsorptive removal of phosphorus from aqueous solution.
AB  - The choice of substrates with high phosphorus adsorption capacity is vital for
      sustainable phosphorus removal from waste water in constructed wetlands. In this
      study, four substrates were used: quartz sand, anthracite, shale and biological
      ceramsite. These substrate samples were characterized by Xray diffractometry and
      scanning electron microscopy studies for their mineral components (chemical
      components) and surface characteristics. The dynamic experimental results
      revealed the following ranking order for total phosphorus (TP) removal
      efficiency: anthracite > biological ceramsite > shale > quartz sand. The
      adsorptive removal capacities for TP using anthracite, biological ceramsite,
      shale and quartz sand were 85.87, 81.44, 59.65, and 55.98 mg/kg, respectively.
      Phosphorus desorption was also studied to analyze the substrates' adsorption
      efficiency in wastewater treatment as well as the substrates' ability to be
      reused for treatment. It was noted that the removal performance for the different
      forms of phosphorus was dependent on the nature of the substrate and the
      adsorption mechanism. A comparative analysis showed that the removal of
      particulate phosphorus was much easier using shale. Whereas anthracite had the
      highest soluble reactive phosphorus (SRP) adsorptive capacity, biological
      ceramsite had the highest dissolved organic phosphorus (DOP) removal capacity.
      Phosphorus removal by shale and biological ceramsite was mainly through chemical
      adsorption, precipitation or biological adsorption. On the other hand, phosphorus
      removal through physical adsorption (electrostatic attraction or ion exchange)
      was dominant in anthracite and quartz sand.

PMID- 25076540
TI  - Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes
      loaded with palladium nanoparticles.
AB  - Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes
      loaded with palladium (Pd) nanoparticles was studied for the first time. The
      effects of Pd loading, dye concentration and reuse repetitions of membranes were
      investigated. In reduction, the dye concentration decreased whereas the pH rose
      gradually. An optimal Pd loading was found. The catalytic membranes were able to
      be reused more than 3 times.

PMID- 25076541
TI  - Debromination of decabromodiphenyl ether by organo-montmorillonite-supported
      nanoscale zero-valent iron: preparation, characterization and influence factors.
AB  - An organo-montmorillonite-supported nanoscale zero-valent iron material (M-NZVI)
      was synthesized to degrade decabromodiphenyl ether (BDE-209). The results showed
      that nanoscale zero-valent iron had good dispersion on organo-montmorillonite and
      was present as a core-shell structure with a particle size range of nanoscale
      iron between 30-90 nm, characterized by XRD, SEM, TEM, XRF, ICP-AES, and XPS. The
      results of the degradation of BDE-209 by M-NZVI showed that the efficiency of M
      NZVI in removing BDE-209 was much higher than that of NZVI. The efficiency of M
      NZVI in removing BDE-209 decreased as the pH and the initial dissolved oxygen
      content of the reaction solution increased, but increased as the proportion of
      water in the reaction solution increased.

PMID- 25076542
TI  - Reinforcement of the pulmonary artery autograft with a polyglactin and
      polydioxanone mesh in the Ross operation: experimental study in growing lamb.
AB  - BACKGROUND AND AIM OF THE STUDY: Synthetic materials used for pulmonary autograft
      (PA) reinforcement in the Ross procedure fail to match the demand for structural
      growth, have only a limited longevity, and do not guarantee adequate vascular
      compliance in high-pressure load systems. The study aim was to develop a
      resorbable reinforcement of a PA, tailored to provide structural support and to
      guide the process of wall structure modification for the preservation of graft
      viability. METHODS: An experimental model of translocation of the pulmonary trunk
      as an autograft in the aortic position was developed and performed under
      cardiopulmonary bypass in young lambs. The PA was left without reinforcement,
      reinforced with standard commercially available mesh, or reinforced with
      resorbable mesh of polyglactin and polydioxanone. RESULTS: Based on vessel
      diameter measurements by transesophageal echography at day 0 and at six months
      postoperatively, only the PA with resorbable reinforcement showed a behavior
      similar to that of the normal aorta in a growing lamb. With the non-resorbable
      reinforcement, transmural migration of the mesh was observed, accompanied by a
      conspicuous inflammatory infiltrate and fibrosis. CONCLUSION: The resorbable mesh
      allowed for histological wall modification, characterized by the presence of
      highly organized smooth muscle cells and elastic lamellae in the media. The
      mechanical and histological features of this resorbable mesh-reinforced PA may be
      crucial to the clinical long-term success of the Ross procedure.

PMID- 25076543
TI  - Aortic prosthesis-patient mismatch strongly affects early results of double valve
      replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The aim of this retrospective single-center
      study was to assess the authors' results in mitral-aortic double valve
      replacement (DVR), with attention focused on the risk factors of in-hospital
      mortality (HM). As the initial results showed a strong relationship between HM
      and aortic prosthesis-patient mismatch (PPM), this led to an assessment of the
      impact of PPM on the early results of DVR. METHODS: Data from 196 consecutive
      patients (mean age 60 +/- 10 years) who had undergone DVR between January 1996
      and December 2011 at the authors' institution were analyzed. A statistical
      comparison was made of groups defined by the presence/absence of in-hospital
      death, postoperative complications, and aortic PPM. A logistic regression
      analysis of the factors associated with HM and their postoperative evolution was
      also conducted. RESULTS: Surgery was mostly performed on an elective basis
      (89.3%), using mainly bileaflet mechanical valves (93.9%). The rate of associated
      coronary bypass (CABG) was 11.2%. Aortic PPM (i.e., an effective orifice area
      index (EOAI) < or = 0.85 cm2/m2) was noted in 28.1% of patients. HM (6.63%) was
      significantly related to PPM (p < 0.002), greater age (p < 0.003), a smaller EOAI
      (p = 0.005), associated CABG (p < 0.008), and a longer aortic cross-clamp time (p
      < 0.03). Patients with aortic PPM had a significantly worse early outcome, with
      higher overall (p < 0.0007) and cardiac (p < 0.05) complication rates, a longer
      intensive care unit stay (p < 0.03), and an almost six-fold higher rate of HM
      (16.4% versus 2.8%; p < 0.002). PPM and age as risk factors were included in a
      predictive model of HM based on logistic regression; a similar model for
      postoperative complications highlighted PPM, age and cardiopulmonary bypass time
      as significant risk factors. CONCLUSION: Aortic PPM greatly affects the
      postoperative outcome of DVR, as it is related to an increased complication rate
      and a higher in-hospital mortality. A strategy of avoiding PPM but without taking
      additional risks might improve the early results of DVR.

PMID- 25076544
TI  - Aortic valve regurgitation secondary to ectopia and atresia of the left main
      coronary artery.
AB  - Congenital atresia of the LMCA is an extremely rare anomaly which is often
      clinically complicated by silent angina, myocardial infarction, failure to
      thrive, or sudden cardiac death. Moreover, the atretic and ectopic origin of the
      LMCA associated with aortic valve anomalies is an even rarer condition. Herein,
      the case is described of a patient with a very rare association between the
      ectopic and atretic left main coronary artery (LMCA) and severe aortic valve
      regurgitation.

PMID- 25076545
TI  - Does a minimally invasive approach increase the incidence of patient-prosthesis
      mismatch in aortic valve replacement?
AB  - BACKGROUND AND AIM OF THE STUDY: The impact of a minimally invasive approach on
      patient-prosthesis mismatch (PPM) in patients undergoing aortic valve replacement
      (AVR) remains unknown. The study aim was to identify the impact of a minimally
      invasive approach for AVR on the incidence of PPM. METHODS: The results of a
      single-center experience in 506 patients who underwent isolated AVR through a
      minimally invasive or conventional sternotomy were analyzed. Postoperative PPM
      was defined as an effective orifice area index < 0.85 cm2/m2, and was correlated
      with surgical approach, mortality and cardiac events after surgery. RESULTS:
      Overall, postoperative PPM was present in 26.0% of the patients. The ratio of PPM
      was 24.1% in minimal access patients and 27.7% in conventional AVR patients (p =
      0.35). Hospital mortality was similar in both groups (3.8% versus 3.4%, p =
      0.62). The body mass index (BMI) was higher in patients with PPM (28.5 +/- 4.4
      versus 25.3 +/- 3.6 kg/m2; p = 0.0001), but obesity was significantly associated
      with PPM (36.3% versus 9.4%; p = 0.0001). The PPM group included more patients
      with a left ventricular ejection fraction (LVEF) < 0.50 (12.8% versus 5.3%; p =
      0.004). The independent risk factors for PPM were increased BMI (p = 0.0001),
      LVEF < 0.50 (p = 0.007) and preoperative aortic stenosis (p = 0.029). A LVEF <
      0.50 increased the risk for PPM by 3.77-fold (95% CI: 1.4-9.9), while a high BMI
      increased the risk by 1.42-fold (95% CI: 1.3-1.5). Preoperative aortic
      insufficiency was associated with PPM, but did not significantly increase the
      risk. CONCLUSION: A minimally invasive approach for AVR did not lead to an
      increased incidence of PPM and associated adverse events following surgery.

PMID- 25076546
TI  - Recurrent native and prosthetic mitral valve thrombosis in idiopathic
      hypereosinophilic syndrome.
AB  - Hypereosinophilic syndrome (HES) is defined as a prolonged, unexplained
      peripheral eosinophilia. Endomyocardial fibrosis and mural thrombus formation are
      common occurrences such that patients are exposed to lethal thromboembolic
      complications. The valvular damage described is mainly related to iterative valve
      thromboses that are amenable to surgery. Here, the case is reported of a 39-year
      old woman suffering from HES with mitral valve thrombosis and mechanical
      prosthetic mitral valve replacement, in whom a new thrombosis of the inserted
      prosthesis occurred one month postoperatively, concomitant with severe
      hypereosinophilia and despite adequate anticoagulation. The patient had received
      a new bioprosthetic mitral valve replacement, and her eosinophil count had been
      normalized after treatment with corticosteroids. Oral anticoagulation with
      warfarin was maintained. Subsequently, no recurrent thromboembolic events were
      reported, and echocardiography performed at the one-year follow up showed the
      bioprosthesis to have a normal hemodynamic profile.

PMID- 25076547
TI  - Hemodynamic comparison of mitral valve repair: techniques for a flail anterior
      leaflet.
AB  - BACKGROUND AND AIM OF THE STUDY: Anterior leaflet flail resulting from elongated
      or ruptured marginal chordae is frequently diagnosed among adults, and is
      amenable to surgical repair. The study aim was to investigate the efficacy of
      three surgical techniques, namely neochordoplasty, limited triangular resection
      and edge-to-edge repair, to correct anterior leaflet flail in an in-vitro
      experimental model. METHODS: Seven porcine mitral valves were evaluated in a
      pulsatile heart simulator before surgical manipulation, after anterior marginal
      chordae transection, and with each surgical repair. Marginal chordal transection
      induced leaflet flail with moderate mitral regurgitation (MR). Following the
      confirmation of MR via direct flow measurements, it was corrected by three
      repairs: neochordoplasty with ePTFE sutures, limited triangular resection, and
      edge-to-edge repair. The post-repair valve hemodynamics were quantified under
      pulsatile conditions of 120 mmHg peak transmitral pressure and 5 l/min cardiac
      output at 70 beats/min. Hemodynamic, geometric and echocardiographic indices were
      also measured. RESULTS: Transecting the marginal chordae induced A2 prolapse and
      produced the regurgitant fraction to 18.7 +/- 10.2%. Surgical repair effectively
      reduced the regurgitant fraction to 6.9 +/- 6.3% (p = 0.019 to prolapse, p =
      0.0117 to baseline) with neochordae, to 5.8 +/- 7.0% (p = 0.03 to prolapse, p =
      0.0378 to baseline) with triangular resection, and to 13.3 +/- 10.2% (p = 0.2091
      to prolapse, p = 0.0045 to baseline) with edge-to-edge repair. Remnant
      regurgitation was largest with edge-to-edge repair compared to limited leaflet
      resection and neochordoplasty, though central leaflet coaptation was restored
      equally by the three repairs, with mild systolic leaflet restriction after
      repair. CONCLUSION: Anterior leaflet repair and a reduction in MR is achievable
      with the three techniques, although neochordoplasty and triangular resection
      proved superior to edge-to-edge repair in eliminating MR.

PMID- 25076548
TI  - Contractile reserve induced with dobutamine echocardiography predicts outcome in
      patients with left ventricular dysfunction and mitral regurgitation.
AB  - BACKGROUND AND AIM OF THE STUDY: The appropriate management of patients with
      mitral regurgitation (MR) and left ventricular dysfunction (LVD) is
      controversial. The study aim was to determine whether the presence of contractile
      reserve (CR) assessed by dobutamine stress echocardiography (DSE) was associated
      with improved outcomes. METHODS: Death and heart transplantation were analyzed as
      the primary outcomes associated with the presence of CR. A total of 125
      consecutive patients (96 males, 29 females; mean age 60 +/- 12 years) with left
      ventricular ejection fraction (LVEF) < or = 35% and hemodynamically significant
      MR underwent DSE between 1999 and 2005. CR was defined as an increase in LVEF of
      > or = 10% during dobutamine infusion. RESULTS: Among 125 patients, 55 (43.0%)
      showed evidence of CR. Within five years after DSE, 24 patients (34.3%) in the CR
      group and seven (12.7%) in the CR+ group had died or required heart
      transplantation (p < 0.01, log rank). After adjusting for age, baseline LVEF,
      NYHA class and moderate/severe tricuspid regurgitation (TR), CR remained an
      independent predictor of time to death or heart transplantation (HR 0.34; 95% CI:
      0.15-0.76, p < 0.01). Improvement in the degree of MR was present at one year in
      85.0% of CR+ patients, and in 62.5% of CR- patients (p = 0.03). An improvement of
      5% in LVEF was noted in the CR+ group, compared to 0% in the CR- group (p =
      0.04). CONCLUSION: In patients with advanced LVD and severe MR, CR detected by
      DSE was associated with significant reductions in the risk of death and heart
      transplantation.

PMID- 25076549
TI  - Spatial relationship of coronary sinus-great cardiac vein with adjoining anatomic
      structures: a key element in predicting the success of percutaneous transvenous
      mitral annuloplasty.
AB  - BACKGROUND AND AIM OF THE STUDY: Knowledge of the anatomy of the coronary venous
      system and its relationship with the mitral valve annulus (MVA) and coronary
      arteries is a key element to successful percutaneous transvenous mitral
      annuloplasty (PTMA) device implantation for treating patients with severe mitral
      regurgitation. METHODS: The spatial relationship of the coronary sinus-great
      cardiac vein (CS-GCV) with the MVA, left circumflex coronary artery (LCx) and its
      branches was examined in 120 formalin-fixed adult human cadaveric hearts.
      RESULTS: During the initial part of its journey, the CS-GCV was seen to course
      along and parallel to the plane of the MVA in 109 cases (90.8%), and to cross the
      MVA obliquely in 11 cases (9.2%). The LCx crossed deep or superficial to the CS
      GCV at a discrete point in 98 cases (81.6%) and in eight cases (6.6%),
      respectively. In two cases (1.6%), the LCx was overlapped by the CS-GCV for an
      average length of 3.5 +/- 0.7 cm, and in five cases (4.1%) it lay superficial to
      the CS-GCV for an average length of 3.1 +/- 1.0 cm. In the remaining seven cases
      (5.8%), the artery did not accompany the CS-GCV along the MVA. Obtuse marginal
      arteries and the ramus intermedius were seen coursing deep to the CS-GCV in 40
      cases (33.3%) and 33 cases (27.5%), respectively. CONCLUSION: The study results
      showed that the CS-GCV crosses the annulus obliquely in 9.2% of cases, and hence
      might affect the efficiency of PTMA. Similarly, positioning of the annuloplasty
      device in the CS-GCV in cases where the LCx and its branches lay deep to the vein
      may result in an impingement of the arteries, leading to ischemia.

PMID- 25076550
TI  - Mitral annular morphology in mitral valve disease with three-dimensional
      transesophageal echocardiography.
AB  - BACKGROUND AND AIM OF THE STUDY: Three-dimensional (3D) transesophageal
      echocardiography (TEE) is useful for the quantification of mitral valve
      structures. The study aim was to investigate, in quantitative manner, any
      differences in mitral valve anatomy among patients with mitral valve prolapse
      (MVP) or functional mitral regurgitation (FMR), compared to normal control
      subjects. METHODS: 3D-TEE was performed in 20 MVP patients, 10 FMR patients and
      in 15 control subjects. Analyses of the full-volume 3D mitral valve data sets
      were performed offline, using Q-Lab software. RESULTS: Distinctive patterns were
      identified in annular geometric changes in normal subjects compared to patients
      with MVP or FMR. Patients with FMR showed significant annular anterior to
      posterior dilatation (34.6 +/- 8.3 mm versus 28.4 +/- 2.9 mm, p < 0.04: FMR
      versus control), whereas in patients with MVP dilatation in the anterolateral to
      posteromedial diameter was more prominent (41.0 +/- 5.9 mm versus 36.6 +/- 2.4
      mm, p < 0.03; MVP versus control). CONCLUSION: 3D-TEE represents a useful method
      for the evaluation of mitral valve geometry.

PMID- 25076551
TI  - Evidence of tricuspid valve remodeling in patients with severe mitral
      regurgitation independently of degree of functional tricuspid regurgitation: a
      two- and three-dimensional echocardiographic study.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate whether, in
      patients with severe mitral regurgitation (MR), tricuspid valve remodeling was
      independent of the degree of functional tricuspid regurgitation (FTR) present.
      Whether any differences in the analysis remodeling, as assessed by two
      dimensional (2D) and three-dimensional (3D) echocardiography, can be demonstrated
      was also addressed. METHODS: A total of 188 patients (mean age 63.5 +/- 16.0
      years) with severe organic or functional MR with or without associated FTR, and
      30 normal controls (mean age 59.2 +/- 15 years) were enrolled in the study.
      Subsequently, both 2D and 3D transthoracic anatomic and functional parameters of
      the tricuspid valve were analyzed. RESULTS: Patients and controls differed in all
      2D and 3D parameters of tricuspid valve remodeling, except for the 2D end
      diastolic annular diameter and circularity indices. The patients were then
      allocated to either group A (trivial/mild FTR) or group B (moderate/severe FTR).
      Significant differences were identified between groups A and B compared to
      controls in all tricuspid valve remodeling indices, except for the diastolic 2D
      annular diameter and circularity indices. Groups A and B had similar 2D and 3D
      parameters of tricuspid valve remodeling. The right ventricular end-diastolic
      diameter (RVEDD) (beta = 0.24, 95% CI: 0.11 to 0.22, p = 0.02) and fractional
      area change (beta = -0.48, 95% CI: -0.24 to 0.09, p = 0.0001, R2 = 0.22) were
      independent predictors of the tenting area, whereas the RVEDD was the only
      independent predictor of the diastolic 3D tricuspid annular area (beta = 0.53,
      95% CI: 1.2 to 2.7, p = 0.0001, R2 = 0.28). CONCLUSION: In patients with severe
      MR, tricuspid valve remodeling was also demonstrated in those with trivial/mild
      FTR, but was better characterized by 3D echocardiography. Tricuspid valve
      remodeling and right ventricular dilation were the main determinants of tricuspid
      valve regurgitation.

PMID- 25076552
TI  - Tricuspid valve replacement: the effect of gender on operative results.
AB  - BACKGROUND AND AIM OF THE STUDY: Tricuspid valve replacement (TVR) is considered
      a high-risk operation. The study aim was to analyze the authors' eight-year
      experience with TVR and to characterize the specific risk factors for this
      operation. METHODS: Between January 2005 and August 2012, a total of 67 patients
      (46 females, 21 males; mean age 58 +/- 14 years; range: 25-86 years) underwent
      TVR at the authors' center. Re-do operations were performed in 48 patients (72%),
      including 37 patients (55%) who had at least two previous surgeries. Isolated TVR
      was performed in 28 patients (42%). The follow up (mean 28 months) included
      echocardiography and survival analysis. RESULTS: The overall operative mortality
      was 17.9% (n = 12, all female). In the latter half of the study period, mortality
      declined to 11.4% (p = NS). Major postoperative morbidity included prolonged
      mechanical ventilation (28.4%), low cardiac output (29.8%), and acute renal
      failure requiring hemodialysis (10.4%). Univariate analysis revealed that female
      gender (p = 0.007), NYHA class (p = 0.038), serum bilirubin level (p = 0.02) and
      number of previous cardiac surgeries (p = 0.05) were associated with increased
      operative mortality. Multivariable analysis demonstrated that reoperation (OR
      6.06, p = 0.036) was an independent risk factor for operative mortality or
      complications. Echocardiography at follow up showed that 92.6% of all patients
      had tricuspid regurgitation grade < 2. The overall five-year survival rates for
      males and females were 82% and 53%, respectively (p = 0.03), but five-year
      survival for operative survivors was similar in males and females (82% versus
      73%, p = 0.5). Cox regression analysis showed that age (OR 1.07, p = 0.028) and
      reoperation (OR 6.1, p = 0.038) were independent risk factors for late mortality.
      CONCLUSION: TVR remains a high-risk operation, particularly for advanced age and
      previously operated patients; however, the long-term survival is satisfactory.
      Typically, women undergo TVR at an older age with a higher mortality rate than
      men. However, the long-term mortality rate of patients who survived surgery was
      not associated with gender.

PMID- 25076553
TI  - An iatrogenic atrioventricular septal defect that developed following
      transfemoral TAVI.
AB  - Transcatheter aortic valve implantation (TAVI) is sometimes associated with
      severe complications due to the unpredictability of such closed-chest procedures.
      Reported complications include atrioventricular blocks, vascular complications,
      aortic root rupture, aorto-right ventricular fistulas, and aortic dissections.
      Herein is presented the case of an 88-year-old female with a late
      atrioventricular septal defect that developed after TAVI.

PMID- 25076554
TI  - Ceftaroline for the treatment of prosthetic valve endocarditis due to methicillin
      resistant Staphylococcus aureus.
AB  - The case is described of a frail patient who developed prosthetic valve
      endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA).
      Conventional antimicrobial treatments either failed or were contraindicated, and
      the patient was judged unsuitable for a further valve replacement. A salvage
      therapy with high doses of a new cephalosporin, ceftaroline, given three times
      daily was undertaken; subsequently, the patient had not relapsed at two months
      after completing a six-week course of ceftaroline. Ceftaroline deserves major
      attention as an alternative choice in difficult-to-treat MRSA endocarditis.

PMID- 25076555
TI  - Value of serum fibrinogen levels in the assessment of mechanical prosthetic valve
      thrombosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The evaluation of prosthetic valve thrombosis
      (PVT) is crucial due to higher mortality and morbidity rates. The study aim was
      to assess the value of fibrinogen in the diagnosis of PVT, an important and a
      common cause of prosthetic valve failure. METHODS: Between December 2007 and
      April 2012, 154 patients with PVT and 116 control subjects with a normally
      functioning prosthesis were enrolled in the study. PVT was diagnosed using
      transesophageal echocardiography, and fibrinogen levels were measured at
      presentation. The patients and controls had similar demographic features.
      RESULTS: NYHA functional class, ineffective anticoagulation, presence of symptoms
      and moderate to severe left atrial spontaneous echo contrast (LASEC) were
      significantly different between the groups. The fibrinogen level was
      significantly higher in patients with PVT compared to controls (393.46 +/- 127.87
      versus 276.93 +/- 69.22 mg/dl, p < 0.001). Ineffective anticoagulation, the
      presence of symptoms, a poor NYHA functional class, the presence of moderate to
      severe LASEC and elevated fibrinogen levels were independent predictors of PVT on
      multivariate regression analysis (p < 0.001, odds ratio (OR) 38.811, 95%
      confidence interval (CI): 13.319-113.091; p < 0.001, OR 6.745, CI: 2.777-16.386;
      p = 0.031, OR 3.557, CI: 1.126-11.239; p = 0.026, OR 3.203, CI: 1.146-8.955, and
      p < 0.001, OR 1.011, CI: 1.007-1.016 respectively). CONCLUSION: Besides known
      indicators of PVT, including ineffective anticoagulation, the presence of LASEC
      and decreased NYHA functional capacity, elevated fibrinogen levels may be a
      valuable marker for the assessment of PVT.

PMID- 25076556
TI  - Redo valvular surgery in elderly patients aged > 75 years.
AB  - BACKGROUND AND AIM OF THE STUDY: Very few data exist regarding the clinical
      outcome of redo valvular surgery in patients aged > 75 years. METHODS: A
      retrospective analysis was conducted of 42 consecutive patients (mean age 78.3
      years) who had undergone redo valvular surgery between January 1991 and December
      2010, and who had been followed up for a mean of 2.5 years. Factors associated
      with early outcomes were analyzed using logistic regression analysis, while
      predictors of late death and valve-related events were identified using Cox
      regression analysis. RESULTS: The overall hospital mortality rate of redo
      procedures was 17%. Multivariate logistic regression analysis showed that
      prolonged ventilator support (OR 1.007; 95% CI: 1.000-1.014; p < 0.0464) was an
      independent risk factor for hospital mortality. Overall survival rates at one and
      three years were 78.3 +/- 6.8% and 67.1 +/- 8.6%, respectively. Multivariate Cox
      regression analysis of survival revealed that age (HR 1.399; 95% CI: 1.044-1.875;
      p < 0.0238) and prolonged ventilator support (HR 1.004; 95% CI: 1.001-1.006; p <
      0.0051) were negative predictors of mid-term survival. Rates of freedom for valve
      related events at one and three years were 77.4 +/- 7.5% and 60.2 +/- 9.6%,
      respectively. An absence of peripheral artery disease protected against valve
      related events (HR 0.045; 95% CI: 0.004-0.44; p < 0.0080). CONCLUSION: Early and
      late outcomes for elderly patients who had undergone redo valvular surgery were
      relatively poor and satisfactory, respectively. Hence, an optimal referral for
      redo surgery is important to achieve better outcomes.

PMID- 25076557
TI  - Subclinical rheumatic heart disease in an Eritrean high-school population,
      detected by echocardiography.
AB  - BACKGROUND AND AIM OF THE STUDY: In developing countries rheumatic heart disease
      (RHD) is still the most common acquired cardiovascular disease affecting children
      and young adults. The study aim was to investigate, via an echocardiographic
      screening, the prevalence of subclinical RHD in high-school students in Eritrea.
      METHODS: A total of 684 students (314 females, 370 males; mean age 16.7 years)
      was randomly selected from nine secondary high schools in different regions of
      Eritrea to assess, via clinical and echocardiographic examinations, the presence
      of subclinical RHD. The term 'subclinical' was used to define the disease at its
      early stage, when it could not be detected by clinical examination only. RESULTS:
      Evidence of RHD was found in 28 students (4%), and of suspected RHD in 23
      students (3.3%). Only 26 students (51%) with RHD (both evident or suspected) had
      a murmur at cardiac auscultation, and only 25 (49%) had a history of previous
      sore throat and tonsillitis. No student had clinical symptoms. All students with
      evident or suspected RHD were sent to secondary prophylaxis. CONCLUSION: Despite
      involving only a limited population sample, the present study confirmed that, in
      Eritrea, there is a high prevalence (4%) of RHD among high-school-aged students.
      The data acquired demonstrated the importance of a clinical and echocardiographic
      surveillance, and the need to start a preventive campaign for rheumatic fever and
      RHD in this country. This has now been commenced in Eritrean primary schools,
      with the collaboration of local teachers.

PMID- 25076558
TI  - The outcomes of triple-valve surgery: eleven years' experience from a single
      center.
AB  - BACKGROUND AND AIM OF THE STUDY: Triple-valve surgery is a challenging and
      complex procedure with significant risk, even at centers experienced at
      performing such operations. The study aim was to investigate the early and late
      outcomes of this surgery, performed at a single center for the past 11 years.
      METHODS: A total of 45 consecutive patients (19 males, 26 females; mean age 69.42
      +/- 12.72 years) underwent triple-valve surgery at the authors' institution
      between 2000 and 2011. The mean logistic EuroSCORE was 22.46 +/- 12.8%. The most
      common aortic valve pathology was calcific degeneration (40%), while the mitral
      valves were mostly rheumatic (31%) or degenerative (26%). The tricuspid valve
      pathology was functional regurgitation in 64% of patients. The aortic valve
      procedures were all replacements, while the mitral valves were either repaired (n
      = 20) or replaced (n = 25). The tricuspid valves were almost exclusively repaired
      (n = 43). Univariate and multivariate analyses were performed to highlight
      predictors of mortality. A Kaplan-Meier analysis was also performed. RESULTS: The
      operative mortality was 8.9% (n = 4). Survival at one, three, and five years was
      91%, 85.5% and 66.4%, respectively. Morbidity was not particularly high: the
      incidence of all postoperative neurological complications was 13%, that of
      transient renal impairment was 18%, and pacemaker implantation 8.9%. CONCLUSION:
      The results of triple-valve surgery were considerably improved compared to
      historical reports. Early mortality was close to that occurring after less
      complex procedures, while late survival was comparable to that after single-valve
      surgery. It is believed that the best results are achieved by centers experienced
      in valve procedures. Compared to older studies, rheumatic disease was not the
      most frequent requirement for of triple-valve surgery among the present patients.

PMID- 25076559
TI  - Function and expression differences between ergot and non-ergot dopamine D2
      agonists on heart valve interstitial cells.
AB  - BACKGROUND AND AIM OF THE STUDY: The symptoms of Parkinson's disease are
      alleviated by dopamine D2 agonists, which are classified as ergot dopamine D2
      agonists and non-ergot D2 agonists. Among the former, pergolide has been
      associated with valvular heart disease, since it has both potent D2 receptor and
      serotonin 5-HT(2B) receptor agonistic properties. Among the latter, pramipexole
      has few incidences of heart valve disease onset, since it has an absence of 5
      HT(2B) receptor agonism. METHOD: A [3H]thymidine incorporation assay was
      performed to monitor function, and microarray global analysis to monitor gene
      expression, on porcine heart valve interstitial cells (VICs) treated with
      pergolide or pramipexole. RESULTS: The 5-HT(2B) receptor was abundantly expressed
      in porcine VICs. The 5-HT(2B) receptor agonist pergolide induced an increase in
      [3H]thymidine incorporation, accompanied by a decrease in 5-HT(2B) receptor mRNA
      expression. [3H]thymidine incorporation was blocked by lisuride, a 5-HT(2B)
      receptor antagonist, and also by LY-294002, a specific inhibitor of PI3K and Akt.
      Moreover, type 2 iodothyronine deiodinase (Dio2) expression in porcine VICs
      treated with pergolide was shown, by a global analysis of mRNA, to be markedly
      increased compared to that induced by pramipexole. Such changes in VICs may
      correlate with the mechanism of heart valve disease pathogenesis. CONCLUSION:
      There were substantial differences (increased [3H]thymidine incorporation, and
      Dio2 expression) between pergolide and pramipexole, which might correlate with
      the mechanism of heart valve disease onset.

PMID- 25076560
TI  - Sutureless Perceval aortic valve in comparison with the stented Carpentier
      Edwards Perimount aortic valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The Sorin Perceval S (SP) sutureless
      bioprosthesis was developed as an advancement of conventional biological aortic
      valve replacement (AVR) with stented bioprostheses, and perhaps also as an
      alternative to the transcatheter aortic valve implantation (TAVI) procedure,
      especially for high-risk patients. Herein are described the authors' early
      results with SP valve replacement, compared to AVR with Carpentier-Edwards
      Perimount (EP) stented valves. METHODS: Between September 2012 and February 2013,
      a total of 14 patients was enrolled in a single-center SP study group, and their
      data were analyzed in a prospective manner. For comparison, 14 patients who
      received an EP valve replacement during the same period were matched with the SP
      group, in a retrospective manner. Hemodynamic parameters and clinical outcome
      were monitored until discharge of the patients in order to analyze the early
      results of the two groups. RESULTS: The cardiopulmonary bypass (CPB) and aortic
      cross-clamp (ACC) times needed for AVR with SP valves were significantly shorter
      than with EP valves. The mean CPB time for SP valve replacement without
      concomitant procedures was 58.4 +/- 11.0 min, compared to 71.8 +/- 11.3 min in
      the EP group (p = 0.015), while the mean ACC times were 37.3 +/- 6.8 and 49.1 +/-
      11.2 min, respectively (p = 0.006). Permanent pacemaker implantation was required
      in four patients after SP valve replacement, but in only one patient after EP
      valve replacement (p = 0.326). The mean transprosthetic peak and mean gradients
      were 24.8 +/- 5.2 mmHg and 13.3 +/- 3.3 mmHg, respectively, in the SP group, and
      19.0 +/- 6.5 mmHg and 10.4 +/- 3.0 mmHg, respectively, in the EP group (p = 0.024
      and p = 0.087). The mean valve size was 23.8 +/- 1.3 mm and 23.3 +/- 1.5 mm in
      the SP and EP groups, respectively. The fall in platelet count after SP valve
      replacement was 180.4 +/- 79.4 x 10(3)/microl on the first postoperative day
      (POD), and 114.1 +/- 51.2 x 10(3)/microl with a minimum of 42 x 10(3)/microl and
      a maximum of 230 x 10(3)/microl at the nadir on POD 2.6 +/- 4.0. The mean minimum
      values at the nadir corresponded to 40% of the initial preoperative value.
      CONCLUSION: The sutureless SP bioprosthesis seems to represent a good alternative
      to conventional stented bioprostheses, especially in older patients with a high
      risk profile, and particularly if concomitant surgical procedures are planned.

PMID- 25076561
TI  - I'm feeling proud.

PMID- 25076563
TI  - Survey: digital health tools making a difference.

PMID- 25076562
TI  - Signing off: memories and meaning.

PMID- 25076564
TI  - The power of longhand.

PMID- 25076565
TI  - Cancer cells propelled by jet power.

PMID- 25076566
TI  - My brain made me eat it.

PMID- 25076567
TI  - Increasing stress to fight back against depression.

PMID- 25076568
TI  - Early preventive dental care lacking.

PMID- 25076569
TI  - Occupational hazards: compassion fatigue, vicarious trauma and burnout.

PMID- 25076570
TI  - The voice of nursing policy.

PMID- 25076571
TI  - The rewards of northern nursing.

PMID- 25076572
TI  - And the Jeanne Mance award goes to...

PMID- 25076573
TI  - Awarding excellence.

PMID- 25076574
TI  - Employer recognition awards.

PMID- 25076575
TI  - Canadian and Chinese RNs to collaborate.

PMID- 25076576
TI  - Putting housing first.

PMID- 25076577
TI  - When mental illness and the justice system intersect.

PMID- 25076578
TI  - Creating a safe harbour.

PMID- 25076579
TI  - What's in your police record?

PMID- 25076580
TI  - It's time to say goodbye.

PMID- 25076581
TI  - The shift in dentistry.

PMID- 25076582
TI  - The shift in dentistry.

PMID- 25076583
TI  - The shift in dentistry.

PMID- 25076585
TI  - Few benefits in two-stage treatment for class II division I malocclusion.

PMID- 25076584
TI  - License to practice.

PMID- 25076586
TI  - Improved periodontal health and slowed atherosclerosis.

PMID- 25076587
TI  - U.S. Task Force unable to recommend for or against oral cancer screenings by
      physicians.

PMID- 25076588
TI  - Study: surgery first shows better survival than chemo for tongue cancer.

PMID- 25076589
TI  - Controversies in dentistry.

PMID- 25076590
TI  - Dentistry at the crossroads.
AB  - The dental practice pattern is shifting from small dental office to large
      corporate dental groups. This article analyzes the powers behind this change, and
      discusses the choices dental practitioners are facing and the reasons why many
      may choose to work in a corporate practice setting. Dental associations and
      specialty groups need to reaffirm their mission to provide quality oral health
      care. Dental treatment should not be viewed as a commodity used to measure
      corporate profitability.

PMID- 25076591
TI  - The perfect storm.

PMID- 25076592
TI  - Academic dentistry in the 21st century: professional dental education or
      development of a trade guild.
AB  - Over the last decade, 10 new dental schools have been established and several
      more are on the drawing board for the near future. The overlying philosophy for
      this new generation of dental school is driven by a combination of societal and
      financial issues. As with many profound changes in educational philosophy, sooner
      or later there are always the unintended consequences that must be confronted.
      This article addresses several of the potential consequences.

PMID- 25076593
TI  - Decision dilemmas and opportunities for the new graduate dentist.
AB  - Career options for new graduate dentists are changing because of economic and
      management challenges in traditional practice, the growing trend toward group
      practice models, enormous educational debt load and lifestyle expectations of the
      millennial dentist. While new dentists learn to survive and adapt to an evolving
      profession with many pitfalls, they also have the opportunity to shape the future
      of our profession.

PMID- 25076594
TI  - Who will tend the dental safety net?
AB  - The dental safety net relates to the sites, providers, programs and payer sources
      that are available to low-income people in households with incomes less than
      three times the federal poverty level. Thirty percent of the population of
      California depends upon the health care safety net. Proposed solutions to meeting
      the safety net's dental needs challenge conventional thinking about who is
      responsible for providing oral health care and what safety net groups gain
      improved access.

PMID- 25076595
TI  - Electronic clinical records: having the right data to navigate through the
      perfect storm.
AB  - U.S. health care is converting from paper to digital information management. This
      conversion has passed the tipping point and is showing evidence of the benefits.
      Yet effective clinical information systems for dentistry have barely begun to be
      adopted. Dentistry is changing and the new practice models will require digital
      information management, as there is increasing pressure for evidence-based
      practice, continuity of care and demonstration of the quality of care resulting
      from these models.

PMID- 25076596
TI  - Transitioning in or out of an insurance contract.

PMID- 25076597
TI  - Use of botox in dentistry is a fine line.

PMID- 25076598
TI  - Access to patient records.

PMID- 25076599
TI  - Retirement: it's not for sissies.

PMID- 25076600
TI  - QA-ing QA.

PMID- 25076601
TI  - Making quality improvement programs more effective.
AB  - PURPOSE: In the past 25 years, and as recent as 2011, all external evaluations of
      the Quality Improvement Organization (QIO) Program have found its impact to be
      small or difficult to discern. The QIO program costs about $200 million on
      average to administer each year to improve quality of healthcare for people of 65
      years or older. The program was created to address questionable quality of care.
      QIOs review how care is provided based on performance measures. The paper aims to
      discuss these issues. DESIGN/METHODOLOGY/APPROACH: In 2012, the author supported
      the production of quarterly reports and reviewed internal monitoring and
      evaluation protocols of the program. The task also required reviewing all
      previous program evaluations. The task involved many conversations about the
      complexities of the program, why impact is difficult to discern and possible ways
      for eventual improvement. Process flow charts were created to simulate the data
      life cycle and discrete event models were created based on the sequence of data
      collection and reporting to identify gaps in data flow. FINDINGS: The internal
      evaluation uncovered data gaps within the program. The need for a system of
      specification rules for data conceptualization, collection, distribution,
      discovery, analysis and repurposing is clear. There were data inconsistencies and
      difficulty of integrating data from one instance of measurement to the next. The
      lack of good and reliable data makes it difficult to discern true impact.
      PRACTICAL IMPLICATIONS: The prescription is for a formal data policy or data
      governance structure to integrate and document all aspects of the data life
      cycle. The specification rules for governance are exemplified by the Data
      Documentation Initiative and the requirements published by the Data Governance
      Institute. The elements are all in place for a solid foundation of the data
      governance structure. These recommendations will increase the value of program
      data. ORIGINALITY/VALUE: The model specifies which agency units must be included
      in the governance authority and the data team. The model prescribes in detail a
      data governance model to address gaps in the life cycle. These prescriptive
      measures will allow the program to integrate all of its data. Without this formal
      data governance structure, the QIO program will be undetermined by the persistent
      lack of good data for monitoring and evaluation.

PMID- 25076602
TI  - Moving to patient reported collection of race and ethnicity data: implementation
      and impact in ten hospitals.
AB  - PURPOSE: The purpose of this paper is to examine the feasibility of collecting
      standardized, patient reported race and ethnicity (RE) data in hospitals, and to
      assess the impact on data quality and utility. DESIGN/METHODOLOGY/APPROACH: Part
      of a larger evaluation that included a comprehensive assessment. Sites documented
      RE data collection procedures before and after program implementation. Primary
      data collected through qualitative interviewing with key respondents in ten
      hospitals to assess implementation. Nine hospitals provided RE data on the same
      patients before and after implementation new data collection procedures were
      implemented to assess impact. FINDINGS: Implementation went smoothly in nine of
      ten hospitals and had substantial effects on the hospital staff awareness on the
      potential for disparities within their hospitals. New procedures had minimal
      impact on characterization of readmitted patients. PRACTICAL IMPLICATIONS: This
      study demonstrated that it is feasible for staff in a diverse group of hospitals
      to implement systematic, internally standardized methods to collect self-reported
      RE data from patients. ORIGINALITY/VALUE: Although this study found little impact
      patients' demographic characterizations, other benefits included greater
      awareness of and attention to disparities, uncovering small pockets of
      minorities, and dramatically increased RE data use in quality improvement
      efforts.

PMID- 25076603
TI  - Why is your patient sedated?
AB  - PURPOSE: The purpose of this paper is to examine the recording of clinical
      indication for prescribed sedative/hypnotic (SH) medications in a large, acute
      tertiary referral hospital. DESIGN/METHODOLOGY/APPROACH: All hospital inpatients'
      medications (n = 367) were audited for prescription details regarding SH
      medications. Medical notes were then examined for evidence of a recorded
      indication for such medications. FINDINGS: SH medications were prescribed to many
      hospital inpatients (42.5 per cent) during admission. An indication was
      documented in the nursing or medical records for 24.4 per cent of patients who
      were prescribed such medications. Nurses rather than by doctors prescribed most
      SH medications (74 vs 26 per cent, respectively, p = 0.003). Some patients
      receiving SH medications were both over 65 and impaired in their mobility (19.2
      per cent). The treatment indication was documented in 47 per cent. PRACTICAL
      IMPLICATIONS: Most patients prescribed SH medications have nothing in their
      medical record explaining why these drugs are being used, including half of the
      elderly, less mobile patients. All health professionals dealing with SH
      medications and doctors in particular need to justify the use of such medications
      in the medical record. For the particularly high-risk groups where SH medications
      are potentially more dangerous, explicit guidance on why and how such medications
      are to be used must be provided by prescribers. ORIGINALITY/VALUE: For the first
      time, data are presented on documentation rates for clinical indication of
      prescribed SH medications across a large acute hospital, and highlights
      significant shortcomings in practice. This study should inform other
      organisations of the need to be mindful of facilitating greater compliance with
      good prescribing practice.

PMID- 25076604
TI  - Quality of care and health professional burnout: narrative literature review.
AB  - PURPOSE: Quality of care and health professional burnout are important issues in
      their own right, however, relatively few studies have examined both. The purpose
      of this paper is to explore quality of care and health professional burnout in
      hospital settings. DESIGN/METHODOLOGY/APPROACH: The paper is a narrative
      literature review of quality of care and health professional burnout in hospital
      settings published in peer-reviewed journals between January 2000 and March 2013.
      Papers were identified via a search of PsychInfo, PubMed, Embase and CINNAHL
      electronic databases. In total, 30 papers which measured and/or discussed both
      quality of care and health professional burnout were identified. FINDINGS: The
      paper provides insight into the key health workforce-planning issues,
      specifically staffing levels and workloads, which impact upon health professional
      burnout and quality of care. The evidence from the review literature suggests
      that health professionals face heavier and increasingly complex workloads, even
      when staffing levels and/or patient-staff ratios remain unchanged.
      ORIGINALITY/VALUE: The narrative literature review suggests that weak retention
      rates, high turnover, heavy workloads, low staffing levels and/or staffing
      shortages conspire to create a difficult working environment for health
      professionals, one in which they may struggle to provide high-quality care and
      which may also contribute to health professional burnout. The review demonstrates
      that health workforce planning concerns, such as these, impact on health
      professional burnout and on the ability of health professionals to deliver
      quality care. The review also demonstrates that most of the published papers
      published between 2000 and 2013 addressing health professional burnout and
      quality of care were nursing focused.

PMID- 25076605
TI  - Diabetic retinopathy care--an international quality comparison.
AB  - PURPOSE: The purpose of this paper is to study the quality indicator
      appropriateness and use it for international quality comparison on diabetic
      retinopathy (DR) patient care process in one American and one Dutch eye hospital.
      DESIGN/METHODOLOGY/APPROACH: A 17-item DR quality indicator set was composed
      based on a literature review and systematically applied in two hospitals.
      Qualitative analysis entailed document study and 12 semi-structured face-to-face
      interviews with ophthalmologists, managers, and board members of the two
      hospitals. FINDINGS: While the medical-clinical approach to DR treatment in both
      hospitals was similar, differences were found in quality of care perception and
      operationalization. Neither hospital systematically used outcome indicators for
      DR care. On the process level, the authors found larger differences. Similarities
      and differences were found in the structure of both hospitals. The hospitals'
      particular contexts influenced the interpretation and use of quality indicators.
      PRACTICAL IMPLICATIONS: Although quality indicators and quality comparison
      between hospitals are increasingly used in international settings, important
      local differences influence their application. Context should be taken into
      account. Since that context is locally bound and directly linked to hospital
      setting, caution should be used interpreting the results of quality comparison
      studies. ORIGINALITY/VALUE: International quality comparison is increasingly
      suggested as a useful way to improve healthcare. Little is known, however, about
      the appropriateness and use of quality indicators in local hospital care
      practices.

PMID- 25076606
TI  - Why TQM does not work in Iranian healthcare organisations.
AB  - PURPOSE: Despite the potential benefits of total quality management (TQM), many
      healthcare organisations encountered difficulties in its implementation. The
      purpose of this paper is to explore the barriers to successful implementation of
      TQM in healthcare organisations of Iran. DESIGN/METHODOLOGY/APPROACH: This study
      involved a mixed research design. In-depth interviews were conducted with TQM
      practitioners to explore TQM implementation obstacles in Iranian healthcare
      organisations. In addition, this study involved survey-based research on the
      obstacles associated with successful TQM transformation. FINDINGS: TQM
      implementation and its impact depend on the ability of managers to adopt and
      adapt its values and concepts in professional healthcare organisations.
      Unsuccessful TQM efforts in Iranian healthcare organisations can be attributed to
      the non-holistic approach adopted in its implementation, inadequate knowledge of
      managers' about TQM implementation, frequent top management turnover, poor
      planning, vague and short-termed improvement goals, lack of consistent managers'
      and employees' commitment to and involvement in TQM implementation, lack of a
      corporate quality culture, lack of team orientation, lack of continuous education
      and training and lack of customer focus. Human resource problems, cultural and
      strategic problems were the most important obstacles to TQM successful
      implementation, respectively. PRACTICAL IMPLICATIONS: Understanding the factors
      that are likely to obstruct TQM implementation would enable managers to develop
      more viable strategies for achieving business excellence. ORIGINALITY/VALUE:
      Understanding the factors that are likely to obstruct TQM implementation will
      help organisations in planning better TQM models.

PMID- 25076607
TI  - Improving process quality for pediatric emergency department.
AB  - PURPOSE: Overcrowding in emergency departments (EDs) leads to longer waiting
      times and results in higher number of patients leaving the ED without being seen
      by a physician. EDs need to improve quality for patients' waiting time and length
      of stay (LoS) from the perspective of process and flow control management. The
      paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: The
      retrospective case study was performed using the computerized ED patient time
      logs from arrival to discharge between July 1, 2009 and June 30, 2010. Patients
      were divided into two groups either adult or pediatric with a cutoff age of 18.
      Patients' characteristics were measured by arrival time periods, waiting times
      before being seen by a physician, total LoS and acuity levels. A discrete event
      simulation was applied to the comparison of quality performance measures.
      FINDINGS: Statistically significant differences were found between the two groups
      in terms of arrival times, acuity levels, waiting time stratified for various
      arrival times and acuity levels. The process quality for pediatric patients could
      be improved by redesign of patient flow management and medical resource. RESEARCH
      LIMITATIONS/IMPLICATIONS: The results are limited to a case of one community and
      ED. This study did not analyze the characteristic of leaving the ED without being
      seen by a physician. PRACTICAL IMPLICATIONS: Separation of pediatric patients
      from adult patients in an ED can reduce the waiting time before being seen by a
      physician and the total staying time in the ED for pediatric patients. It can
      also lessen the chances for pediatric patients to leave the ED without being seen
      by a physician. ORIGINALITY/VALUE: A process and flow control management scheme
      based on patient group characteristics may improve service quality and lead to a
      better patient satisfaction in ED.

PMID- 25076608
TI  - Evaluation of the use of a nurse-administered telephone questionnaire for post
      operative cataract surgery review.
AB  - PURPOSE: The purpose of this paper is to determine the safety of substituting the
      first day post-operative review after routine cataract surgery
      (phacoemulsification) with a telephone survey. DESIGN/METHODOLOGY/APPROACH:
      Prospective non-randomised cohort study. A standardised questionnaire of five
      common ocular symptoms (general condition, vision, eye pain, headache, nausea or
      vomiting) was administered by a trained nurse on the first post-operative day.
      The patients were reviewed in clinic two to 14 days later. Patient charts were
      retrospectively reviewed for complications (endophthalmitis, raised intra-ocular
      pressure, wound leaks and uveitis) requiring deviation from standard treatment.
      FINDINGS: Over 13 months, 256 eyes of 238 patients underwent uncomplicated
      phacoemulsification by four consultant surgeons. Only one patient reported poor
      general condition, blurred vision and eye pain. She was subsequently found to
      have corneal oedema and raised intra-ocular pressure when recalled for an earlier
      review. Best corrected visual acuity better than 20/40 was achieved in 80.5 per
      cent of patients. There were no other post-operative complications noted from
      medical records review. RESEARCH LIMITATIONS/IMPLICATIONS: Non-randomised nature,
      skewed surgical expertise, lack of a control group and patient experience data.
      In all, 22 patients (9.2 per cent) were also uncontactable for the telephone
      interview. PRACTICAL IMPLICATIONS: A nurse-administered telephone survey seemed
      to be a safe and effective alternative to first day post-operative review after
      routine phacoemulsification. The survey also enabled the detection of serious
      post-operative complications. The first day post-operative hospital visit may be
      safely substituted in a selected patient population with greater patient
      convenience achieved and liberation of clinic resources. ORIGINALITY/VALUE: This
      is the first study which utilises a standardised questionnaire as a form of post
      operative review in an Asian population.

PMID- 25076609
TI  - The Joint Commission cracks down on vial misuse in hospitals.
AB  - Unsafe injection practices with respect to the misuse and unsafe use of vials is
      being targeted by The Joint Commission (TJC). The accrediting agency has issued a
      Sentinel Event Alert, putting hospitals on notice that they need to take strong
      steps to insure that health care workers fully understand and are carrying out
      practices that protect patients from the dangers of vial misuse. According to the
      Centers for Disease Control (CDC) in Atlanta, since 2001, at least 49 outbreaks
      related to the mishandling of injectable medical products have occurred, and
      during this time period, more than 150,000 patients have had to be notified to
      undergo blood-borne pathogen testing because of their potential exposure to
      unsafe injections. TJC cites a survey of 5,446 health care practitioners, which
      reveals significant gaps in basic infection control practices related to vial
      use. Experts suggest vial misuse is often due to a lack of understanding of how
      to apply safe injection practices. To make improvements, experts recommend that
      hospital administrators first take steps to observe what is happening in their
      care environments, and then develop targeted action plans.

PMID- 25076610
TI  - Tele-mental health brings expert input to EPs, speeds treatment.
AB  - Faced with rising demand from patients with mental health problems, Mercy San
      Juan Medical Center in Carmichael, CA, is using telemedicine to connect many of
      these patients with psychiatrists. With input from the psychiatrists, emergency
      physicians feel more comfortable initiating treatment for these patients, many of
      whom can then be discharged with instructions to pursue outpatient follow-up.
      Further, the expert consults help physicians determine whether patients who have
      been placed on involuntary holds require inpatient treatment or can be safely
      treated and discharged. The technology required for the remote sessions is
      contained on robots that can move from room to room in the ED. The ED targets two
      groups of patients for tele-mental health visits: patients who present with
      concerns that the emergency physicians do not feel comfortable treating without
      input from psychiatrists, and patients who have been in the ED for an extended
      period of time, and it is clear that they will not be transported to an inpatient
      psychiatric facility any time soon. Currently, 25%-30% of the mental health
      patients who present to the ED are being touched by the remote psychiatrists;
      however, administrators are looking to increase that percentage to 50%-75%. They
      are also interested in potentially conducting regular rounds of the mental health
      patients with the remote psychiatrists.

PMID- 25076611
TI  - ED-based pharmacists make a big dent in medication errors.
AB  - When Children's Medical Center in Dallas, TX, decided to place specially trained
      pharmacists on site in the ED around the clock, medication errors went from 8% to
      less than 1%.The pharmacists review every order that is written before a
      medication ever reaches a patient, and they are on hand to provide guidance to
      physicians, nurses, and patients in real time. Their input is clearly valued:
      Administrators estimate that when pharmacists suggest a change to a provider's
      medication decision, that suggestion is adopted 75%-90% of the time. According to
      research, hospital medication errors are three times more likely to occur in
      pediatric populations than adults. Children's Medical Center employs 10 on-site
      pharmacists in the ED with 24/7 coverage. Pharmacists are part of the care team
      for all of the critical care patients who come through the ED, and they are
      available to provide guidance to providers and nurses on medication-related
      issues. At times, nurses call on the pharmacists to speak with patients or
      families about their medications--especially in cases with complicated medication
      regimens.

PMID- 25076612
TI  - Kids still getting codeine despite harmful effects.

PMID- 25076613
TI  - Why did you join?

PMID- 25076614
TI  - Maximize efficiency, reduce stress--hire an RDAEF2.

PMID- 25076616
TI  - Stem cells from teeth can make brain-like cells.

PMID- 25076615
TI  - Ethical principles as smoke screens.

PMID- 25076617
TI  - New study reveals rationales for anesthesia decisions.

PMID- 25076618
TI  - Perio bacteria spur cancer growth in mouth.

PMID- 25076619
TI  - Osteoporosis drugs linked to jawbone destruction.

PMID- 25076620
TI  - Custom-made mouthguards reduce concussion risk.

PMID- 25076621
TI  - Mutation found in jaw tumor: world's first.

PMID- 25076622
TI  - Cultural and linguistic competency E-learning program for oral health
      professionals.

PMID- 25076623
TI  - T cell isolation may lead to oral disease research.

PMID- 25076624
TI  - New grafting procedure for oral implantation.

PMID- 25076625
TI  - Rare bone diseases and their dental, oral, craniofacial manifestations.

PMID- 25076626
TI  - Medical management of dental caries.

PMID- 25076627
TI  - Management of patients with active caries.
AB  - This paper reports on a mechanism to manage caries as a disease and to medically
      intervene in the disease process to halt progression. The goal of this paper is
      to provide this alternative to a surgical-only approach. The management of caries
      begins with assessing lesion activity and the potential for arrest. This requires
      a clinical and radiological assessment and evaluation of risk. Hopeless teeth are
      extracted and large cavities filled to reduce infection. Risk reduction
      strategies are employed so efforts to arrest lesions can be successful. Teeth
      with lesions in the enamel or outer third of the dentin should be sealed, not
      restored, as restorations can weaken teeth and can be traumatic to pulps.

PMID- 25076628
TI  - Prevention and nonsurgical management of dental caries over the life course for
      individuals with special health care needs.
AB  - Traditional approaches to caries prevention and management are unlikely to result
      in successful outcomes for individuals with special health care needs. Intensive
      prevention-oriented and minimally invasive restorative approaches have the
      greatest potential to address oral health disparities affecting vulnerable
      populations. This paper introduces readers to oral health-related issues for
      patients with special health care needs across the life course and outlines
      clinical strategies to prevent and manage caries in high-risk patients.

PMID- 25076630
TI  - You set the tone.

PMID- 25076629
TI  - Promoting oral health through community engagement.
AB  - Persistent health disparities still exist in the U.S. despite decades of focus on
      the importance of prevention. Individual behaviors are the major contributor to
      oral health. By partnering and linking with community organizations, oral health
      professionals can expand their reach, overcome the obstacles to delivering
      effective prevention activities in dental offices and improve the oral health of
      the most underserved and vulnerable populations, who bear the greatest burden of
      dental disease.

PMID- 25076631
TI  - Minimizing vicarious liability for employee actions.

PMID- 25076632
TI  - Prescription Drug Monitoring Program.

PMID- 25076633
TI  - Dentistry: the early years.

PMID- 25076634
TI  - The roller-coaster image of the VA.

PMID- 25076635
TI  - Building strong partnerships with CMOs.
AB  - CFOs and chief medical officers (CMOs) can build on common traits to form
      productive partnerships in guiding healthcare organizations through the changes
      affecting the industry. CFOs can strengthen bonds with CMOs by taking steps to
      engage physicians on their own turf--by visiting clinical locations and attending
      medical-executive committee meetings, for example. Steps CFOs can take to help
      CMOs become more acquainted with the financial operations of health systems
      include demonstrating the impact of clinical decisions on costs and inviting CMOs
      to attend finance-related meetings.

PMID- 25076636
TI  - Aligning physician compensation with strategic goals.
AB  - In 2012, Mayo Clinic Health System (MCHS) had 13 different physician compensation
      models among its operating units, with most based on productivity metrics. MCHS
      aimed to transition all physicians to a single compensation model that would
      facilitate its integration with Mayo Clinic and promote physician engagement with
      emerging value-based payment models. The new model, which was implemented this
      past January, incorporates quality metrics, provides physicians with regular
      reports of their performance, and already has resulted in greater physician
      attention to outcomes, safety, and patient experience.

PMID- 25076637
TI  - Building the right physician compensation model.
AB  - In using benchmark data from physician surveys to establish physician
      compensation, hospitals should follow six guidelines: Know what the benchmark
      data represent and how they are computed. Use all resources available in setting
      physician compensation. Carefully determine whether the median work relative
      value unit should be used. Beware of applying consistent compensation models
      across specialties. Be careful not to change the compensation rates annually.
      Think holistically.

PMID- 25076638
TI  - Developing a CIN for strategic value.
AB  - Clinically integrated networks (CINs) allow health systems and independent
      physicians to join in a mutually beneficial effort to adapt to new payment
      models. Key issues during planning for a CIN include organizational structure and
      governance, payer contracts, and incentive funds distribution. In assessing the
      network's potential financial impact, CIN planners should think in terms of
      managing total cost of care rather than in terms of revenues for care delivered.

PMID- 25076639
TI  - Strategies for redesigning physician compensation.
AB  - Five principles should guide a health system's efforts to redesign its physician
      compensation plan: Goals should be aligned. Goals should not focus solely on
      productivity. Metrics should be not only individual, but also team-based. Initial
      metrics should be selected from among those currently being used. Compensation
      plans should avoid long-term commitments.

PMID- 25076640
TI  - Why revisit your cost-accounting strategy.
AB  - Healthcare entities seeking to develop effective cost-accounting systems should
      take six steps to avoid potential pitfalls: Secure broad executive-level support
      for the effort. Ensure systems are in place to analyze the disparate data. Define
      measurable objectives to ensure that implementation achieves desired results.
      Give due consideration to implementation planning. Train support staff
      sufficiently to avoid underutilization. Develop a sufficiently broad base of
      staff support for the system.

PMID- 25076641
TI  - It's academic.

PMID- 25076642
TI  - Evaluating third-party or self-development of non-acute care facilities.

PMID- 25076643
TI  - Social work: a profession of power, passion, and purpose.

PMID- 25076644
TI  - The Social Work Reinvestment Initiative: advocacy and social work practice.
AB  - In 2006, NASW launched the Social Work Reinvestment Initiative by granting each
      state chapter $15,000 in seed money to address the most pressing social work
      needs in the state. This article describes how NASW-SD, with 246 members,
      launched an epic campaign that resulted in the establishment of the only MSW
      program in South Dakota. Using historical research methods, this article
      demonstrates the power of social work advocacy when members unify in pursuit of a
      common goal and describes how the social workers rallied to educate policymakers
      and the public on the value of social work and its delivery of necessary social
      services at all levels and in all fields of practice. The research highlights an
      uphill battle of advocacy and the skillful planning and implementation of a
      campaign to secure state funding to establish the first MSW program in the state,
      at the beginning of the most difficult economic recession since the Great
      Depression.

PMID- 25076645
TI  - Finding joy in social work. II: Intrapersonal sources.
AB  - Despite the social work profession's strengths orientation, research on its
      workforce tends to focus on problems (for example, depression, problem drinking,
      compassion fatigue, burnout). In contrast, this study explored ways in which
      social workers find joy in their work. The authors used an appreciative inquiry
      approach, semistructured interviews (N = 26), and a collaborative grounded theory
      method of analysis. Participants identified interpersonal (making connections and
      making a difference) and intrapersonal (making meaning and making a life) sources
      of joy and reflected significant personal initiative in the process of finding
      joy. The authors present findings regarding these intrapersonal sources of joy.

PMID- 25076646
TI  - Bridging the gap between research-supported interventions and everyday social
      work practice: a new approach.
AB  - This article describes a rationale for a focus on case studies that would provide
      a database of single-group pre-post mean effect sizes that could be analyzed to
      identify which service provision characteristics are associated with more
      desirable outcomes when interventions supported by randomized clinical trials are
      adapted in everyday practice settings. In addition, meta-analyses are proposed
      that would provide benchmarks that agency practitioners could compare with their
      mean effect size to inform their decisions about whether to continue, modify, or
      replace existing efforts to adopt or adapt a specific research-supported
      treatment. Social workers should be at the forefront of the recommended studies
      in light of the profession's emphasis on applied research in real-world settings
      and the prominence of social work practitioners in such settings.

PMID- 25076647
TI  - Descriptive analysis of individual and community factors among African American
      youths in urban public housing.
AB  - African American adolescents are disproportionately represented in urban public
      housing developments. These neighborhoods are generally characterized by high
      rates of poverty, crime, violence, and disorganization. Although evidence is
      emerging on youths in these communities, little is known about their depressive
      symptoms, perceived efficacy, or frequency of substance use and sex-risk
      behavior. Further, even less is known about their exposure to community and
      household violence, their parents' behavior, or their sense of connection to
      their communities. Using a sample of 782 African American adolescents living in
      public housing neighborhoods located in four large U.S. cities, this article
      attempts to rectify the observed gap in knowledge by presenting a descriptive
      overview of their self-reported depressive symptoms; self-efficacy; frequencies
      of delinquent and sexual-risk behavior; and alcohol, tobacco, and other drug use.
      The self-reported ratings of their parents' behavior as well as their exposure to
      community and household violence are presented. Analytic procedures include
      descriptive statistics and mean comparisons between genders and across research
      cities. Results suggest several differences between genders and across research
      sites. However, results are not very different from national data. Implications
      for social work practice are discussed.

PMID- 25076648
TI  - Significance of after-school programming for immigrant children during middle
      childhood: opportunities for school social work.
AB  - School social workers and other school personnel can find meeting the educational
      and social needs of immigrant children a challenge, particularly if these
      children are also experiencing poverty and other educational barriers, including
      limited English language proficiency. Quality after-school programming has been
      associated with a variety of positive effects such as increased educational
      attainment and positive social and emotional development and could, therefore,
      prove significant in the lives of immigrant children. Yet, immigrant children
      participate less. The purpose of this article is to discuss ways in which school
      social workers can increase enrollment in after-school programming among
      immigrant children, six to 12 years of age, by becoming both advocates for
      children and families and leaders in developing and maintaining these services.
      School social workers are poised to play a number of roles related to practice,
      administration, research, and policy. Because this particular age group of
      children begins to look beyond the family for guidance and support, middle
      childhood is an opportune time for school social workers to work toward involving
      children in positive after-school experiences.

PMID- 25076649
TI  - Addressing PTSD in low-income victims of intimate partner violence: moving toward
      a comprehensive intervention.
AB  - Research indicates that female victims of intimate partner violence (IPV) are at
      risk for developing posttraumatic stress disorder (PTSD) and other negative
      mental health outcomes. Low-income women of color experience IPV at
      disproportionately high rates and may need a comprehensive array of resources to
      recover from victimization. Although cognitive-behavioral therapy, a
      psychotherapeutic approach, has been established as the most effective treatment
      for PTSD in some populations, psychotherapy may not be sufficient for this
      population of survivors. This article reviews the relevant research and
      literature on treatment approaches for victims of IPV and provides an overview of
      studies investigating more holistic intervention approaches that feature
      components such as social support groups and advocacy, in addition to
      psychotherapy. Relying on conservation of resources theory, which posits a
      relationship between resources and psychological stress, and a relationship
      oriented ecological framework, this article presents a model of a comprehensive
      intervention for disadvantaged minority victims of IPV that can help address
      issues related to PTSD and empower survivors to access necessary resources.

PMID- 25076650
TI  - Traumatic brain injury and the Americans with Disabilities Act: implications for
      the social work profession.
AB  - The practice of social work has been greatly affected by the Americans with
      Disabilities Act of 1990 (ADA). Title I of the statute prohibits discrimination
      against people with disabilities, including the increasing number of workers who
      are returning to work after a traumatic brain injury (TBI). This article examines
      the extent to which the ADA protects those with TBI from being harassed, being
      denied reasonable workplace accommodations, or suffering other adverse actions
      related to perceived discrimination. To do so, it relies on judicial decisions
      from U.S. federal courts involving alleged workplace discrimination of this
      population. Implications for social work practice are noted with the intent of
      increasing ADA awareness among professionals providing services to people who
      meet the criteria for disability under the ADA as well as to those persons who do
      not. The authors hope to encourage social workers to rely on case law analysis as
      a mechanism to provide further evidence of the systematic problems faced by
      people with TBI and thus increase their visibility.

PMID- 25076651
TI  - Social work practitioners' integration of clients' religion and spirituality in
      practice: a literature review.
AB  - Emerging research on religion, spirituality, health, and mental health has begun
      to catch the attention of helping professionals. Some clients are expressing a
      desire for their health and mental health practitioners to initiate discussion of
      their religious or spiritual beliefs as they relate to their case. Social workers
      are the most represented group among personnel providing mental health services,
      so it is important to understand their attitudes, views, and behaviors regarding
      integrating clients' religion and spirituality (RS) into practice. Few studies
      have assessed such an integration; those that are available focus primarily on
      practitioner characteristics and use of specific helping activities to integrate
      clients' RS in treatment. This article discusses how RS have been integrated into
      social work practice and education and reviews instruments used to assess such
      practices. In addition, the findings from previous studies examining social
      workers' integration of clients' RS are compared with those of other helping
      professions. Finally, implications for education and practice are discussed.

PMID- 25076652
TI  - Homophobia is a global issue.

PMID- 25076653
TI  - Gay divorce.

PMID- 25076654
TI  - Community factors shaping early age at first sex among adolescents in Burkina
      Faso, Ghana, Malawi, and Uganda.
AB  - Using data from the National Survey of Adolescents (2004), we examine the
      community-level factors associated with early age at first sex among adolescents
      14-19 years old in four African countries. Regression models are fitted
      separately by sex for each country for an outcome measuring early age at first
      sex, with a focus on community-level factors as potential influences of age on
      sexual debut. The community-level factors associated with adolescents' sexual
      debut vary widely by both country and gender. Community influences that emerge as
      risk or protective factors of early sexual debut include community levels of
      adolescent marriage, wealth, religious group affiliation, sex education, parental
      monitoring, reproductive health knowledge, media exposure, membership in
      adolescent social group, and use of alcohol. Results indicate the importance of
      context-specific understanding of adolescents' sexual behaviour and suggest how
      elements of place should be harnessed in the development of effective HIV and
      sexual health interventions.

PMID- 25076655
TI  - Multiple antibiotic-resistant bacteria on fluted pumpkin leaves, a herb of
      therapeutic value.
AB  - Fluted pumpkin (Telfairia occidentalis) is a minimally-processed green leafy
      vegetable traditionally used for its antianaemic properties in the form of leaf
      juice without a heating or inactivation step before consumption. The aim of the
      study was to assess the presence of surface microbiota on T. occidentalis leaves
      and also to determine the antimicrobial susceptibility of isolated organisms.
      Bacterial contaminants on 50 samples of T. occidentalis leaves were isolated and
      characterized using standard biochemical methods and the antimicrobial
      susceptibility of isolated organisms was determined using the antibiotic disc
      diffusion assay. The results obtained show that the leaves of T. occidentalis is
      contaminated with organisms which included Enterobacter agglomerans (25.9%),
      Proteus vulgaris (24.9%), Klebsiella spp. (2.6%), and Serratia liquefaciens
      (2.1%). Other bacterial isolates recovered in order of frequency included:
      Staphylococcus spp. (33.7%), Bacillus spp. (8.3%), and Pseudomonas fluorescens
      (2.6%). Of the 193 bacterial isolates from the leaves of T. occidentalis samples
      tested for antimicrobial resistance, all (100%) were found to be resistant to
      ampicillin, cloxacillin, augmentin, erythromycin, and tetracycline while 96% of
      the isolates were resistant to cephalothin. Resistance to trimethoprim (93%) and
      gentamicin (83%) was also observed. Approximately, 22% of the isolates were
      resistant to ciprofloxacin; however, only 11 (5.8%) were resistant to ofloxacin.
      Thus, uncooked T. occidentalis is a potential source of highly-resistant
      epiphytic bacteria which could be opportunistic pathogens in consumers.

PMID- 25076656
TI  - Observational follow-up study on a cohort of children with severe pneumonia after
      discharge from a day-care clinic in Dhaka, Bangladesh.
AB  - Compliance, morbidity, mortality, and hospitalization during fortnightly follow
      up were evaluated by an observational study on a cohort of children with severe
      and very severe pneumonia after day-care treatment at an urban clinic. The
      primary outcome measures were proportions of success (compliance) and failure
      (non-compliance) of follow-up visits at the day-care clinic. In total, 251
      children were followed up, with median (IQR) age of 5.0 (3.0-9.0) months, and
      their compliance dropped from 92% at the first to 85% at the sixth visit. Cough
      (28%), fever (20%), and rapid breathing (13%) were common morbidities. Successful
      follow-up visits were possible in 180 (95.2%) and 56 (90.3%) of the children with
      severe and very severe pneumonia respectively. Eleven (4.4%) needed
      hospitalization, and four (1.6%) died. Majority (approximately 90%) of the
      children could be successfully followed up; some failed to attend their scheduled
      follow-up visits due to hospitalization and death. The common morbidities
      indicate the importance of follow-up for detecting medical problems and early
      treatment, thus reducing risk of death.

PMID- 25076657
TI  - Microbial quality of water in rural households of Ethiopia: implications for milk
      safety and public health.
AB  - Waterborne pathogenic agents affect the health of people either by direct
      consumption of contaminated water or by its indirect use in food production
      and/or processing. Studies on the microbiological quality of water in rural areas
      of Ethiopia are still limited, especially at the household level. The aim of the
      present study was to assess the microbial quality of water from different sources
      in rural households in two districts of the Ethiopian Rift Valley area. The
      correlation between E. coli counts in water and milk was also investigated. In
      total, 233 water samples (126 collected in dry and 107 in wet season) and 53 milk
      samples (19 from raw milk and 36 from processed milk products) were analyzed for
      E. coli contamination. The overall prevalence of E. coli in water samples was
      54.9% (n = 233). In most of the analyzed samples, a higher prevalence of E. coli
      was recorded during the wet compared to the dry season. The highest load of E.
      coli was detected in water samples from dugouts. The quality of raw milk and
      traditionally-processed milk products showed variations between districts, and
      the traditionally-processed milk products were found to contain higher E. coli
      loads than raw milk. The correlation between the E. coli counts in water and milk
      only showed a weak but positive relationship (r = 0.1). Taking E. coli as a proxy
      for water quality, the microbiological quality of water consumed in the study
      area was found to be very poor, posing a potential food safety and health risk to
      the rural communities.

PMID- 25076658
TI  - Seasonal dietary intakes and socioeconomic status among women in the Terai of
      Nepal.
AB  - Despite widespread nutritional deficiencies, investigations of usual diet in
      rural South Asia remain sparse. The present study characterizes year-round and
      seasonal dietary patterns of women in the Terai of Nepal by sociodemographic
      status, using a novel, weekly single-visit and usual food frequency questionnaire
      that links recall to the agricultural season. The study was conducted across
      seasons in 2006-2008 among 15,899 women of reproductive age in Sarlahi district.
      Intakes were tabulated for all foods, overall and by socioeconomic status (SES),
      and in and out of season, as appropriate. Foods consumed regularly [median
      (interquartile range) weekly frequency] were rice [13 (7-13)], potatoes [10 (5
      13)], legumes [6 (2-9)], and vegetable oil [13 (13-13)]. Animal products were
      infrequently consumed [1 (0-2) time per week] as were fruits and vegetables, most
      with a median weekly intake frequency of 0. Higher SES was associated with more
      frequent consumption of most food-groups, including in-season fruits and
      vegetables. Diets of women in the Terai of Nepal lack diversity and, likely,
      nutrient adequacy, which may pose health risks.

PMID- 25076659
TI  - Compliance with home-based fortification strategies for delivery of iron and
      zinc: its effect on haematological and growth markers among 6-24 months old
      children in north India.
AB  - Compliance is a key component in successful implementation of the delivery of
      micronutrients among children. The present study evaluates the compliance with
      two home-based food fortification strategies (fortified complementary food or
      sprinkle) for providing iron and zinc among children aged 6-24 months. A total of
      292 children were randomly allocated to receive either rice-based fortified
      complementary food and nutrition education (Cf = 101), sprinkle and nutrition
      education (Mp = 97), or nutrition education alone as control (Ed = 94). All the
      enrolled children were breastfed at the beginning of the study and were advised
      to continue breastfeeding. Biweekly information on compliance and anthropometry
      was collected. Complete haemogram estimation was conducted at baseline and end of
      the study. Compliance with the fortified complementary food was higher compared
      to sprinkle (Cf = 81%, Mp = 64% child-days). Consumption of the fortified
      complementary food for 6 months resulted in a significant increase in mean
      haemoglobin in the intervention group compared to control group (Cf 1.29 +/- 1.6
      g/dL; Ed 0.23 +/- 1.3 g/dL; p < 0.001). Our results showed that fortified
      complementary food had higher compliance than sprinkle and is a suitable delivery
      mechanism for iron and zinc in preschool children.

PMID- 25076660
TI  - Prevalence of household-level food insecurity and its determinants in an urban
      resettlement colony in north India.
AB  - An adequate food intake, in terms of quantity and quality, is a key to healthy
      life. Malnutrition is the most serious consequence of food insecurity and has a
      multitude of health and economic implications. India has the world's largest
      population living in slums, and these have largely been underserved areas. The
      State of Food Insecurity in the World (2012) estimates that India is home to more
      than 217 million undernourished people. Various studies have been conducted to
      assess food insecurity at the global level; however, the literature is limited as
      far as India is concerned. The present study was conducted with the objective of
      documenting the prevalence of food insecurity at the household level and the
      factors determining its existence in an urban slum population of northern India.
      This cross-sectional study was conducted in an urban resettlement colony of South
      Delhi, India. A pre-designed, pre-tested, semi-structured questionnaire was used
      for collecting socioeconomic details and information regarding dietary practices.
      Food insecurity was assessed using Household Food Insecurity Access Scale
      (HFIAS). Logistic regression analysis was performed to determine the factors
      associated with food insecurity. A total of 250 women were interviewed through
      house-to-house survey. Majority of the households were having a nuclear family
      (61.6%), with mean family-size being 5.5 (SD +/- 2.5) and the mean monthly
      household income being INR 9,784 (SD +/- 631). Nearly half (53.3%) of the mean
      monthly household income was spent on food. The study found that a total of 77.2%
      households were food-insecure, with 49.2% households being mildly food-insecure,
      18.8% of the households being moderately food-insecure, and 9.2% of the
      households being severely food-insecure. Higher education of the women handling
      food (OR 0.37, 95% CI 0.15-0.92; p < or = 0.03) and number of earning members in
      the household (OR 0.68, 95% CI 0.48-0.98; p < or = 0.04) were associated with
      lesser chance/odds of being food-insecure. The study demonstrated a high
      prevalence of food insecurity in the marginalized section of the urban society.
      The Government of India needs to adopt urgent measures to combat this problem.

PMID- 25076661
TI  - Relationship between mothers' nutritional knowledge in childcare practices and
      the growth of children living in impoverished rural communities.
AB  - This study assessed the relationship between maternal nutritional knowledge in
      childcare practices and growth of children living in impoverished rural
      communities. This was an analytical cross-sectional study which covered a random
      sample of 991 children aged 0-36 month(s). Multivariate analysis showed that,
      after adjusting for potential confounders, there was a significant positive
      association between the childcare knowledge index and mean HAZ (beta = 0.10, p =
      0.005) but was not associated with mean WHZ. The strength of association
      increased among women of high socioeconomic status (beta = 0.15, p = 0.014) but
      there was no significant association among women of low socioeconomic status.
      Increase in maternal childcare knowledge may contribute significantly to child's
      nutritional status in Ghana if there is concurrent improvement in socioeconomic
      circumstances of women living in deprived rural communities.

PMID- 25076662
TI  - Determinants of early initiation, exclusiveness, and duration of breastfeeding in
      Uganda.
AB  - Breastfeeding practices in Uganda are contrary to the best practice recommended
      by World Health Organization (WHO). Only six in 10 Ugandan children below the age
      of six months are exclusively breastfed. This paper investigated the determinants
      of breastfeeding practices in Uganda. Using the Uganda Demographic and Health
      Survey (UDHS) of 2006, we employed probit and Cox's regression techniques as well
      as the Kaplan-Meier survival functions during the analysis. On average, 56% and
      46% initiated breastfeeding in the first hour and practised exclusive
      breastfeeding respectively while 25%, 50%, and 75% terminated breastfeeding at
      18, 24, and 26 months respectively. The mean number of months of breastfeeding
      was 14.1, and the maximum was 40. Hospital delivery increased the probability of
      early initiation and exclusive breastfeeding by 4-5% (p < 0.01) and 7-8% (p <
      0.01) respectively. Prenatal care increased the probability of early initiation
      and exclusive breastfeeding by 6-7% (p < 0.05) and 5-7% (p < 0.05) respectively.
      Birth intervals less than 24 months increased the risk of early termination of
      breastfeeding by 19% (p < 0.01). Hospital delivery and prenatal care should be
      made a priority, and mothers should be encouraged to adopt higher birth
      intervals.

PMID- 25076663
TI  - Nutritional knowledge, attitude, and practices among pregnant and lactating women
      living with HIV in the Manzini region of Swaziland.
AB  - The prevalence of HIV infection in Swaziland (26%) is among the highest in the
      world. We investigated nutritional knowledge, attitude, and practices (KAP) and
      the influence of sociodemographic factors on KAP among pregnant and lactating
      women living with HIV in the Manzini region of Swaziland. Interviews were
      conducted using a structured questionnaire to collect data from 324 subjects
      seeking healthcare from selected regional hospitals, health centres, and clinics
      in Manzini region. The results showed mean percentage scores of nutritional
      knowledge (67%), attitude (67%), and practices (51%) whereby educational level (p
      = 0.002), employment status (p = 0.009), income (p = 0.008), religion (p =
      0.007), type of accommodation (p = 0.006), type of transport used when going for
      shopping (p = 0.001), and BMI (p = 0.015) were significantly associated with
      nutritional practices. Significant positive correlations between nutritional KAP
      were observed: nutritional K and A (r = 0.155, p = 0.005), nutritional K and P (r
      = 0.456, p = 0.001), and nutritional A and P (r = 0.230, p = 0.001). Multiple
      linear regression analysis indicated that type of transport used when going for
      shopping (p = 0.002), educational level (p = 0.001), income (p = 0.001),
      employment (p = 0.038), knowledge of food proportion in a plate (p = 0.000), a
      positive attitude towards high-fibre diet (p = 0.004), and eating a variety of
      foods (p = 0.006) were predictors of nutritional practices. Educational level was
      identified as a common predictor of nutritional knowledge, attitude, and
      practices, suggesting that both formal and informal education systems are
      potential factors influencing dietary practices among pregnant and lactating
      women living with HIV in Swaziland.

PMID- 25076664
TI  - Prevalence, clinical predictors, and outcome of hypocalcaemia in severely
      malnourished under-five children admitted to an urban hospital in Bangladesh: a
      case-control study.
AB  - Hypocalcaemia is common in severely-malnourished children and is often associated
      with fatal outcome. There is very limited information on the clinical predicting
      factors of hypocalcaemia in hospitalized severely-malnourished under-five
      children. Our objective was to evaluate the prevalence, clinical predicting
      factors, and outcome of hypocalcaemia in such children. In this case-control
      study, all severely-malnourished under-five children (n=333) admitted to the
      Longer Stay Ward (LSW), High Dependency Unit (HDU), and Intensive Care Unit (ICU)
      of the Dhaka Hospital of icddr,b between April 2011 and April 2012, who also had
      their total serum calcium estimated, were enrolled. Those who presented with
      hypocalcaemia (serum calcium <2.12 mmol/L) constituted the cases (n=87), and
      those admitted without hypocalcaemia (n=246) constituted the control group in our
      analysis. The prevalence of hypocalcaemia among severely-malnourished under-five
      children was 26% (87/333). The fatality rate among cases was significantly higher
      than that in the controls (17% vs 5%; p < 0.001). Using logistic regression
      analysis, after adjusting for potential confounders, such as vomiting, abdominal
      distension, and diastolic hypotension, we identified acute watery diarrhoea (AWD)
      (OR 2.19, 95% CI 1.08-4.43, p = 0.030), convulsion on admission (OR 21.86, 95% CI
      2.57-185.86, p = 0.005), and lethargy (OR 2.70, 95% CI 1.633-5.46, p = 0.006) as
      independent predictors of hypocalcaemia in severely-malnourished children. It is
      concluded, severely-malnourished children presenting with hypocalcaemia have an
      increased risk of death than those without hypocalcaemia. AWD, convulsion, and
      lethargy assessed on admission to hospital are the clinical predictors of
      hypocalcaemia in such children. Presence of these features in hospitalized
      children with severe acute malnutrition (SAM) should alert clinicians about the
      possibility of hypocalcaemia and may help undertake potential preventive
      measures, such as calcium supplementation, in addition to other aspects of
      management of such children, especially in the resource-poor settings.

PMID- 25076665
TI  - Impact of individual, household and community characteristics on children's
      nutritional indicators.
AB  - This study analyzed WHO-standardized nutritional indicators of children from
      selected households within communities that were sampled from all districts of
      Botswana. Data from the 2007 Botswana Family Health Survey were fitted into
      multilevel models that seek to account for variability due to the macro- and
      micro-units that have been hierarchically selected. This allowed for estimation
      of different levels of intraclass correlations while simultaneously assessing the
      model-fit by accounting for the influence on the nutritional indicators due to
      the fixed variables attributable to these macro- and micro-units. The results
      show that variation in nutritional status of under-five children in Botswana is a
      function of characteristics of the households and communities within which they
      live. As much as 17% of variation is due to differences in the communities and
      households. Economic status of households holds an important key in predicting
      the nutritional status of children.

PMID- 25076666
TI  - Nutritional quality and price of food hampers distributed by a campus food bank:
      a Canadian experience.
AB  - Food insecurity is a mounting concern among Canadian post-secondary students.
      This study was conducted to evaluate the content of food hampers distributed by
      University of Alberta Campus Food Bank (CFB) and to assess the cost savings to
      students, using these hampers. Contents of hampers distributed among 1,857
      students and their dependants since 2006 were evaluated against Canada's Food
      Guide (CFG) recommendations and Dietary Reference Intakes (DRI). Hampers were
      aimed at serving university students and one to five members of their households
      located in Edmonton, Western Canada. One thousand eight hundred fifty-seven
      clients in Alberta, Canada, were included in the study. Although all hampers
      provided adequate energy, their fat and animal protein contents were low.
      Compared to the CFG recommendations, the requirements of milk and alternatives
      and meat and alternatives were not sufficiently met for clients using > or = 3
      person hampers. None of food hampers (i.e. one- to five-person hampers) met the
      DRI recommendations for vitamin A and zinc. Clients of CFB received Canadian
      dollar (CN$) 14.88 to 64.3 worth of non-perishable food items in one- to five
      person hampers respectively. Hampers provided from the CFB need improvement.
      Nutrients missing from the food hampers could be provided from fresh fruits,
      vegetables, dairy, and meat products; however, these foods are more expensive
      than processed food items. The CFB provides a significant amount of savings to
      its clients even without considering the additional perishable donations that are
      provided to clients. Interpretation of our data required the assumption that all
      clients were consuming all of their hampers, which may not always be the case.
      Clients that do not fully consume their hampers may benefit less from the food
      bank.

PMID- 25076667
TI  - Consanguinity and its sociodemographic differentials in Bhimber District, Azad
      Jammu and Kashmir, Pakistan.
AB  - Kashmiri population in the northeast of Pakistan has strong historical, cultural
      and linguistic affinities with the neighbouring populations of upper Punjab and
      Potohar region of Pakistan. However, the study of consanguineous unions, which
      are customarily practised in many populations of Pakistan, revealed marked
      differences between the Kashmiris and other populations of northern Pakistan with
      respect to the distribution of marriage types and inbreeding coefficient (F). The
      current descriptive epidemiological study carried out in Bhimber district of
      Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that
      consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin
      unions were the predominant type of marriages and constituted 50.13% of total
      marital unions. The estimates of inbreeding coefficient were higher in the
      literate subjects, and consanguinity was witnessed to be rising with increasing
      literacy level. Additionally, consanguinity was observed to be associated with
      ethnicity, family structure, language, and marriage arrangements. Based upon
      these data, a distinct sociobiological structure, with increased stratification
      and higher genomic homozygosity, is expected for this Kashmiri population. In
      this communication, we present detailed distribution of the types of marital
      unions and the incidences of consanguinity and inbreeding coefficient (F) across
      various sociodemographic strata of Bhimber/Mirpuri population. The results of
      this study would have implication not only for other endogamous populations of
      Pakistan but also for the sizeable Kashmiri community immigrated to Europe.

PMID- 25076668
TI  - Developmental screening tools: feasibility of use at primary healthcare level in
      low- and middle-income settings.
AB  - An estimated 150 million children have a disability. Early identification of
      developmental disabilities is a high priority for the World Health Organization
      to allow action to reduce impairments through Gap Action Program on mental
      health. The study identified the feasibility of using the developmental screening
      and monitoring tools for children aged 0-3 year(s) by non-specialist primary
      healthcare providers in low-resource settings. A systematic review of the
      literature was conducted to identify the tools, assess their psychometric
      properties, and feasibility of use in low- and middle-income countries (LMICs).
      Key indicators to examine feasibility in LMICs were derived from a consultation
      with 23 international experts. We identified 426 studies from which 14 tools used
      in LMICs were extracted for further examination. Three tools reported adequate
      psychometric properties and met most of the feasibility criteria. Three tools
      appear promising for use in identifying and monitoring young children with
      disabilities at primary healthcare level in LMICs. Further research and
      development are needed to optimize these tools.

PMID- 25076669
TI  - Obesity epidemic in Brazil and Argentina: a public health concern.
AB  - The obesity epidemic is rapidly advancing in South America, leading to inevitable
      health consequences. Argentinian and Brazilian health policies try to become
      adapted to the new economic and social framework that follows from this epidemic.
      It is in incipient and ineffective control so far since the prevalence of obesity
      was not restrained. The Argentine national legislation is more advanced, through
      the so-called "Ley de Obesidad." In Brazil, there are numerous local initiatives
      but still not a comprehensive law. National policies relating to decisions
      regarding obesity are discussed in this paper. Trends in decisions issued in
      higher courts of Argentina (Supreme Court of Justice of the Nation--CSJN) and
      Brazil (Supreme Court of Justice--STF), in the last 15 years, seek to clarify the
      approach of each country and court's resolutions. Marked differences were found
      in their positions. Finally, legal and health solutions to this obesity epidemic
      are proposed.

PMID- 25076670
TI  - Psychosocial correlates of dietary behaviour in type 2 diabetic women, using a
      behaviour change theory.
AB  - The study evaluated the efficacy of the Theory of Reasoned Action (TRA), along
      with self-efficacy to predict dietary behaviour in a group of Iranian women with
      type 2 diabetes. A sample of 352 diabetic women referred to Khoy Diabetes Clinic,
      Iran, were selected and given a self-administered survey to assess eating
      behaviour, using the extended TRA constructs. Bivariate correlations and Enter
      regression analyses of the extended TRA model were performed with SPSS software.
      Overall, the proposed model explained 31.6% of variance of behavioural intention
      and 21.5% of variance of dietary behaviour. Among the model constructs, self
      efficacy was the strongest predictor of intentions and dietary practice. In
      addition to the model variables, visit intervals of patients and source of
      obtaining information about diabetes from sociodemographic factors were also
      associated with dietary behaviours of the diabetics. This research has
      highlighted the relative importance of the extended TRA constructs upon
      behavioural intention and subsequent behaviour. Therefore, use of the present
      research model in designing educational interventions to increase adherence to
      dietary behaviours among diabetic patients was recommended and emphasized.

PMID- 25076671
TI  - Use of contraceptives and unmet need for family planning among tribal women in
      India and selected hilly states.
AB  - The paper provides a comprehensive picture of knowledge and use of contraceptives
      among scheduled tribes of India and selected central hilly states where tribal
      population contributes more than 30% of the total tribal population of the
      country. An attempt is also made to know how far scheduled tribes differ from non
      tribes in the states, namely Jharkhand, Madhya Pradesh, and Chhattisgarh, using
      information collected in the third round of District-level Household Survey (DLHS
      RCH III: 2007-2008). Bivariate analysis was used for understanding the level of
      knowledge, use of and unmet need for contraception among different tribal and non
      tribal groups. Binary logistic regression was used for understanding the factors
      associated with the use of contraception and unmet need for family planning among
      tribal women. Knowledge and use of temporary contraceptive methods are
      considerably lower among tribal women compared to their non-tribal counterparts
      in the three states under study. Low acceptance due to phobia of adverse health
      consequences, accessibility to and lack of sound knowledge of contraception are
      the leading reasons for not using contraceptives. The unmet need for family
      planning among them was quite high, especially in the state of Jharkhand.
      Multivariate analysis substantiated the role of women and husbands' education,
      age of women, and number of surviving boys in the use of any modem method of
      contraception. Educating women and their respective husbands about proper use and
      benefits of modem contraceptives is important to solve the problem of high unmet
      need for family planning among these tribal women. A simultaneous attention to
      the health systems strengthening component is crucial for ensuring sustained
      delivery of good-quality family planning services.

PMID- 25076672
TI  - Assessing the effectiveness of house-to-house visits on routine oral polio
      immunization completion and tracking of defaulters.
AB  - Strengthening routine immunization is one of the four prongs of the Global Polio
      Eradication Initiative. Using data collected through 30-cluster sample household
      surveys of caretakers of children aged 12-23 months, this paper assessed the
      effectiveness of house-to-house visits on routine oral polio immunization
      completion, using simple frequency tables, bivariate and multivariate logistic
      regression analyses. Logistic regression results demonstrated that children in
      households where the caregivers reported receiving a household visit by health
      workers were more likely to be fully immunized for polio through routine
      immunization than other children, although results were significant only after
      correcting for confounders. In Ethiopia and India, children of caregivers who
      remembered a house-to-house visit were significantly and positively associated
      with routine polio vaccination completion (OR = 2.2 and OR = 2.2 respectively).
      In Angola, the association was positive, though not significant (OR = 1.3). The
      evidence suggests that targeting high-risk areas for house-to-house visits played
      a role in increasing routine polio vaccination.

PMID- 25076673
TI  - Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother.
AB  - In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in
      children, exclusively breastfed ones whose mothers are vegetarian, causing low
      body stores of vitamin B12. The haematologic manifestation of vitamin B12
      deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean
      corpuscular volume and typical morphological features, such as hyperlobulation of
      the nuclei of the granulocytes. In advanced cases, neutropaenia and
      thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In
      addition to haematological symptoms, infants may experience weakness, fatigue,
      failure to thrive, and irritability. Other common findings include pallor,
      glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the
      central nervous system and, in severe cases, rarely cause brain atrophy. Here, we
      report an interesting case, a 12-month old infant, who was admitted with
      neurological symptoms and diagnosed with vitamin B12 deficiency.

PMID- 25076674
TI  - Cutaneous leishmaniasis in an immigrant Saudi worker: a case report.
AB  - Cutaneous leishmaniasis (CL), an uncommon disorder in South-East Asia, including
      Bangladesh, often presents as granulomatous plaque on the exposed areas, with a
      high index of suspicion required for diagnosis. Here we report the first imported
      case of CL caused by Leishmania tropica in a migrant Bangladeshi worker in the
      Kingdom of Saudi Arabia (KSA). The case, initially suspected as a case of
      cutaneous tuberculosis, arrived at specimens reception unit (SRU) of diagnostic
      labs of icddr,b being referred by the physician for ALS testing for tuberculosis.
      At his arrival in the SRU, one of the health personnel of the unit who used to
      work in KSA suspected him as a case of CL. The diagnosis was confirmed by smear
      microscopy which revealed plenty of amastigotes within macrophages. PCR was
      performed to confirm the species. He was treated with sodium stibogluconate at
      Shahid Suhrawardy Medical College Hospital, Dhaka.

PMID- 25076675
TI  - Medicine and politics.

PMID- 25076676
TI  - Leadership development.

PMID- 25076677
TI  - Three initiatives are leading South Dakota physicians into the future.

PMID- 25076678
TI  - Acute myocardial infarction at extremes of adult age presented.

PMID- 25076679
TI  - 18-year-old female with acute ST elevation myocardial infarction.
AB  - Acute coronary syndrome (ACS) is a rare disease entity among young female
      patients. Intra mural hematoma is a diagnostic consideration in a population at
      low risk for classic pathophysiologic mechanisms underlying acute coronary
      syndromes, namely plaque rupture or plaque erosion. We describe a case of a young
      female patient presenting with acute coronary syndrome attributed to intra mural
      hematoma.

PMID- 25076680
TI  - Stenting of the unprotected left main coronary artery in a nonagenarian
      presenting with recurrent non-ST elevation myocardial infarction.
AB  - Coronary artery disease (CAD) involving the left main (LM) artery has
      traditionally been considered an indication for coronary artery bypass surgery
      (CABG). With recent advances in the field of percutaneous coronary interventions
      (PCI), angioplasty and stenting of the unprotected' LM has been performed in
      patients at high surgical risk. This is a challenging intervention as a large
      area of myocardium is at risk during the procedure. Features that make it
      especially high risk are distal stenosis of this vessel and presence of coronary
      disease in other territories. Left ventricular assist devices need to be
      considered in these situations so as to minimize the risk involved. We present a
      case of a 90-year-old female with myocardial infarction who underwent complex
      angioplasty involving the distal LM and proximal left anterior descending (LAD)
      coronary artery, without left ventricular assist device or balloon pump support.

PMID- 25076681
TI  - Death certification: a primer part III--certainty and the unknown cause of death.
AB  - The level of certainty needed to assign a cause of death may be problematic. The
      certification regulations stipulate that a certifier only needs to believe that a
      proposed cause of death be more likely than not (i.e. anything more than fifty
      percent likely). While there is no requirement for absolute certainty in
      completing a death certificate, the consequences of a specific diagnosis (for
      example, a diagnosis of acquired immunodeficiency syndrome) may, at the
      discretion of the certifier, require a higher level of certainty. At times,
      however, a certifier may not know even a more likely than not cause of death. In
      some circumstances where death was not anticipated/expected and a thorough
      postmortem examination fails to establish a cause of death, listing the cause of
      death as unknown or undetermined is perfectly acceptable. Alternatively, death
      occurring in an elderly individual, where death would not be entirely unexpected
      and with no known medical history or stigmata of disease, poses a more difficult
      certification situation. In these situations the certifier may either choose
      unknown for a cause of death, or (preferably in my opinion) choose what he or she
      feels would be the most likely cause of death given the statistical likelihood of
      causes of death in individuals similar to the decedent.

PMID- 25076682
TI  - Preparticipation physical evaluations in youth sports: a systematic review of
      current recommendations.
AB  - BACKGROUND: Participation in youth sports is on the rise in America, and
      discourse exists regarding frequency and content of the preparticipation
      examination (PPE) to best identify risk factors and prevent injury. Our objective
      was to review current recommendations for PPEs proposed by the specialties that
      most commonly perform PPEs: the American Academy of Family Physicians, the
      American Academy of Pediatrics, the American College of Sports Medicine, and the
      National Athletic Trainers' Association. METHODS: The evidence basis for the
      recommendations in PPE Campaign and Coalition for Youth Sports Health and Safety
      Fourth Edition and the National Athletic Trainers' Association (NATA) position
      statement on PPEs were reviewed. Recommendations with a strong empirical basis
      (Category A and B) were distinguished from those which were opinion-based.
      RESULTS: A thorough review of all recommendations revealed only one Category A
      and three Category B recommendations. These recommendations were in the
      categories of orthopedic screening, medical/family history and general health
      screenings. CONCLUSIONS: There is little evidence supporting the effectiveness of
      current recommendations in preventing primary and secondary injury in youth
      sports. The few recommendations which are evidence-based speak to the importance
      of a complete review of medical and family history and performing a thorough
      musculoskeletal exam.

PMID- 25076683
TI  - The impact of health care technology on medication safety.

PMID- 25076684
TI  - I. Practice of medicine--patient engagement.

PMID- 25076685
TI  - Quality focus: QIO program changes.

PMID- 25076686
TI  - DAKOTACARE update: Health coaches: a partner in your patient's care.

PMID- 25076687
TI  - Viral hepatitis C in 2014--the beginning of the end?

PMID- 25076688
TI  - Extra intestinal manifestations and complications in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's
      disease (CD), doesn't affect only the intestinal tract, but also involve other
      organs such as: eyes, skin, joints, liver and biliary tracts, kidneys, lungs,
      vascular system. It is difficult to differentiate the true extraintestinal
      manifestations from secondary extraintestinal complications. The pathogenetic
      autoimmune mechanisms include genetic susceptibility, antigenic display of
      autoantigen, aberrant self-recognition and immunopathogenetic autoantibodies
      against organ-specific cellular antigens shared by colon and extra-colonic
      organs. An important role is owned by microbes due to molecular mimicry. This
      paper reviews the frequency, clinical presentation and therapeutic implications
      of extraintestinal symptoms in inflammatory bowel diseases.

PMID- 25076689
TI  - Cardiac tumors.
AB  - Cardiac tumors are a group of rare disorders with a frequency that varies in
      population studies between 0.0017% and 0.33%. There are primary cardiac tumors
      with an incidence of 5% of all cardiac tumors and secondary tumors (metastases of
      the heart) in 95% of cases. Symptoms are nonspecific and can mimic many other
      heart diseases. This fact makes the diagnosis of cardiac tumors very difficult.
      Approximately 75% of the primary cardiac tumors are benign; the most frequent
      histological type encountered is myxoma in 50% of cases, followed by cardiac
      fibromas, lipomas, rhabdomyomas, hemangiomas, teratomas, papillary
      fibroelastomas, pericardial cysts or cystic tumor of the atrioventricular node
      region. Secondary cardiac tumors (metastases) are 20 times more common than
      primary cardiac tumors. Paraclinical methods (especially imaging evaluation) are
      always necessary for the complete diagnosis: transthoracic and transesophageal
      echocardiograms are the gold standard investigations in the diagnosis of the
      cardiac tumors; CT scans together with MRIs are complementary diagnostic methods
      that are useful when the diagnosis is uncertain. In the majority of cases
      surgical treatment is recommended.

PMID- 25076690
TI  - Pulmonary rehabilitation and quality of life in lung cancer patients.
AB  - Lung cancer is one of the most common types of cancer, often diagnosed in
      advanced stages. Chest surgery is the main component of curative treatment, the
      pre-operative functional status being predictive for post-operative morbidity.
      The potential benefits of pulmonary rehabilitation in lung cancer management
      appear in pre-operative period, improving the exercise capacity and increasing
      the number of patients sent to surgery, in post-operative period, decreasing the
      number of complications, and during the medical treatment of patients with
      advanced disease, improving the symptoms and increasing the quality of life. The
      quality of life (QOL) in patients with lung cancer is determined by factors
      related to patient (stage of disease, co morbidities) as well as treatment
      (surgery, chemotherapy, radiotherapy). The assessment of QOL is made through
      questionnaires, mainly related to therapeutic regimens and symptoms. Among the
      most used are Questionnaire of the European Organization for Research and
      Treatment of Cancer (EORTC QLQ - C30), Functional Assessment of Cancer Therapy -
      General (FACT - G), FACT - L (Lung) and the Lung Cancer Symptom Scale (LCSS).

PMID- 25076691
TI  - Acute cardiogenic pulmonary edema--etiological spectrum and precipitating
      factors.
AB  - AIM: The analysis of the predisposing and precipitating factors encountered in
      the anamnesis of the patients hospitalized with acute pulmonary oedema, in order
      to establish some correlations with the evolution and prognosis. MATERIAL AND
      METHODS: The study included 50 patients, 32 males and 18 females, admitted to the
      Cardiology I Clinic between 2009 and 2013, diagnosed with acute pulmonary oedema
      upon admission. The following aspects were investigated: cardiovascular
      antecedents, prodromal elements of the current episode of acute pulmonary oedema
      (APE), risk factors and associated co morbidities, previous treatments followed
      at home as well as the triggering factors of the acute episode. RESULTS: The main
      pathology on which the acute pulmonary oedema (APE) episode occurred was
      represented by: arterial high blood pressure (HBP), dilated cardiomyopathy,
      ischemic heart disease, valvular heart disease, pre-existing atrial rhythm
      disorders. The analysis of the factors that precipitated the acute pulmonary
      oedema episode revealed the following possible triggering conditions: inadequate
      physical effort on the background of treatment discontinuation, high sodium diet,
      a prolonged ischemic episode due to inadequate physical effort, rhythm disorder
      with rapid ventricular response (atrial fibrillation, atrial flutter). In some
      cases, the risk factors were cumulated. CONCLUSIONS: Acute pulmonary oedema
      represents a major emergency that requires immediate admission to hospital and
      rapid treatment in the emergency department concurrent with the identification of
      the triggering and precipitating factors.

PMID- 25076692
TI  - Thyroid function during the first year of recombinant human growth hormone
      therapy in short stature children.
AB  - INTRODUCTION: The relationship between rhGH treatment and thyroid function has
      been the subject of numerous studies. Some say that rhGH treatment unmasks
      central hypothyroidism, other say that rhGH induces subclinical primary
      hypothyroidism. AIM: To assess the changes in thyroid function in short stature
      children in the first year of treatment with rhGH and the impact on growth
      velocity. MATERIAL AND METHODS: We evaluated 37 patients treated with rhGH, 5
      were excluded because developed side effects during treatment. We measured
      height, height velocity, and height standard deviation gain during treatment and
      thyroid function during the first year of treatment. RESULTS: We observed a
      slight increase in the TSH level and no significant change in the f T4 level
      after the first 3-6 months of treatment in all the groups; in GH deficiency (GHD)
      patients, we observed a statistically significant decrease of the f T4 level
      after the first 3-6 months, without a significant increase of the TSH level.
      After the first year, thyroid function returned to baseline. There were no
      differences between height velocities in all the groups, except from the GHD
      patients. CONCLUSIONS: The slight increase in the TSH level and the decrease of f
      T4 level might unmask a transient subclinical primary hypothyroidism but these
      changes do not influence the growth velocity in first year of rhGH treatment.

PMID- 25076693
TI  - Hyponatremia--risk factor in patients with chronic heart failure--clinical,
      evolutive and therapeutic implications.
AB  - Patients with heart failure are, by definition, hemodynamically unstable. This
      condition may be accentuated by medication (digitalis, diuretics,
      antiarrhythmics), so that they become more sensitive to electrolyte disturbances.
      Hyponatremia is the most common electrolyte disorder, particularly common in the
      intensive care unit. AIM: The evaluation of the incidence of hyponatremia in
      patients diagnosed with chronic heart failure in order to establish a correlation
      with the evolution, prognosis and therapeutic implications. MATERIAL AND METHODS:
      We analyzed retrospectively 120 patients diagnosed with chronic heart failure
      NYHA II-IV classes, admitted in the Cardiology Clinic between 2009 and 2013. We
      analyzed electrolytic disturbances which occurred during different strategies of
      therapy. RESULTS: 120 patients with heart failure were admitted in the Cardiology
      Clinic between 2009 and 2013, 92 males and 28 females. Diagnosis was established
      by classical criteria. Evaluation was very complex and included: complete
      clinical examination, electrocardiogram, echocardiography, chest ray examination
      and biochemical analyses especially hepatic, renal function and electrolyte
      status. CONCLUSIONS: The data obtained showed that electrolyte disturbances are
      frequent in patients with chronic heart failure, irrespective of NYHA class.
      Hyponatremia is usually associated with diuretic therapy and may play a very
      important role in the subsequent development of life-threatening complications.
      Patients with heart failure who develop hyponatremia during their evolution had a
      worse prognosis.

PMID- 25076694
TI  - Assessing the risk of decompensation by ascites and spontaneous bacterial
      peritonitis in cirrhosis.
AB  - AIM: The current trend is to analyze predictive factors of transition from
      compensated to decompensated stage by the onset of ascites and later of
      spontaneous bacterial peritonitis (SBP), which would make possible an early
      diagnosis of liver cirrhosis at the compensated stage. The aim of the study is to
      evaluate patients with liver cirrhosis, assessing the rate and the risk factors
      of decompensation by ascites and SBP. MATERIAL AND METHODS: The prospective study
      included patients with cirrhosis of different etiologies admitted to a ward of
      the Institute of Gastroenterology and Hepatology of Iasi in the period 1st
      January 2010-31st December 2010, which were reassessed clinically and in
      laboratory for 2 years. The essential criteria for the diagnosis of SBP were the
      presence of > 250 PMN/mm3. Compensated cirrhosis was defined as the absence of
      ascites. The presence of ascites and/or upper gastrointestinal hemorrhage (UGH)
      marks the state of decompensated cirrhosis. To assess the severity of liver
      cirrhosis there were used Child-Pugh score and MELD score. Diagnostic
      paracentesis and ascitic fluid sampling were performed at admission to hospital
      and during hospitalization, in the event of signs and symptoms of SBP, after
      antibiotic treatment. Macroscopic, biochemical (albumin, protein), cytological
      (cellularity) and bacteriological (smear and culture) investigations of the
      ascetic fluid were performed. Lack of response to empirical treatment was
      considered in cases of general condition deterioration and decreased PMN < 25% of
      baseline. RESULTS: By comparing the mean values of patients with and without SBP,
      it is noted that bilirubin and creatinine were significantly higher in patients
      with SBP, and total protein, albumin and prothrombin time were significantly
      lower in patients with SBP, these biochemical parameters correlate with the
      degree of hepatic impairment and may be considered risk factors for SBP. In
      relation to the mentioned elements, the most important predictors of PBS risk are
      low protein concentration in ascitic fluid under 1g/dl, increased levels of serum
      bilirubin and low platelet count. Impaired liver function, infectious
      complications, and previous episodes of SBP, UGH are risk factors for an episode
      of SBP. Empirical therapy of nosocomial SBP with third-generation cephalosporins
      is often inefficient due to the high prevalence of multiresistant (MR) bacteria.
      CONCLUSIONS: Assessment of clinically significant portal hypertension (PHT) and
      the degree of hepatic impairment may stratify patients with cirrhosis according
      to the risk of decompensation, making possible the identification of high risk
      patients. The knowledge of the risk factors in SBP is important not only to
      identify patients who could benefit from preventive therapy, but also in
      understanding the pathogenesis of the disease.

PMID- 25076695
TI  - Vitamin D status in patients admitted in a clinic of endocrinology.
AB  - Vitamin D deficiency has been known as a global health problem and there were
      reported moderate to strong inverse associations between 25(OH) D concentrations
      and cardiovascular diseases, serum lipid concentrations, inflammation, glucose
      metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood
      disorders, declining cognitive function, impaired physical functioning, and all
      cause mortality. In Romania there are only a few published reports on vitamin D
      status among adult population. AIM: To evaluate vitamin D status in 440 patients
      those were admitted in our clinic for various endocrine pathology. MATERIAL AND
      METHOD: Serum 25-hydroxy vitamin D was measured using chemiluminescence assay. We
      categorized the vitamin D levels in 3 subgroups (deficiency, insufficiency and
      sufficiency). RESULTS: In our study there was a high prevalence of both vitamin D
      deficiency and insufficiency, while optimal level was observed only in a very
      small number of patients. CONCLUSIONS: We demonstrated a high frequency of
      vitamin D deficiency in general population, especially in elderly and children.
      There are still many controversies regarding the optimal vitamin D status and the
      supplementation dosage, so long-term large scale studies are needed regarding
      efficacy and safety.

PMID- 25076696
TI  - Barriers of antiaggregant treatment.
AB  - In the present study we aimed to evaluate side effects of antiplatelet therapy in
      order to establish correlations with medication type, doses and association with
      other therapies. MATERIAL AND METHODS: In the study we prospectively evaluated a
      cohort of patients who received antiplatelet therapy for different pathologies.
      We included patients with acute coronary syndromes, valvular disease complicated
      with supraventricular arrhythmias (especially atrial fibrillation), carotidal
      critical stenosis, neurologic disease (ischemic or thrombotic), and peripheral
      artery disease. RESULTS AND DISCUSSIONS: The study included 125 patients (85
      males and 40 females), aged between 45 and 85, and admitted in the 1st Cardiology
      Department, St Spiridon Hospital, between January 2012 and December 2013, who
      received antiplatelet therapy for different pathologies. All the patients
      included in the study received platelet antiaggregant therapy with Clopidogrel in
      association or not with Aspirin or low weight molecular heparin. Side effects
      reported (possibly correlated with antiplatelet therapy) were: macroscopic
      hematuria (7 cases), cutaneous ecchymosis (7 cases), purpuric lesions (9 cases),
      gingival bleeding (12 cases), upper gastrointestinal bleeding (6 cases), and
      hemoptysis (2 cases). CONCLUSIONS: Hemorrhagic events under the treatment with
      antiplatelet agents are rare in comparison with the large number of patients
      treated. Clinical manifestations are very different depending on the drug and
      also on the drug-associations used. Hemorrhagic accidents may sometimes be very
      serious, determining the specific therapeutic measures.

PMID- 25076697
TI  - Characteristics of co infection with hepatitis B virus among Romanian patients
      infected with human immunodeficiency virus.
AB  - AIM: To determine the epidemiological and viroimmunological features and outcome
      of HIV/HBV-co infected patients cared in the lasi HIV/AIDS Regional Center.
      MATERIAL AND METHODS: This retrospective study included 252 patients diagnosed
      with HIV infection and associated hepatitis B virus (HBV) infection assessed at
      the Hospital of Infectious Diseases in the interval 2000-2013 and treated with
      antiretroviral drugs active against both HIV and HBV. RESULTS: The prevalence of
      HIV/HBV co infection was 19.9%. A slightly higher frequency of this co infection
      was found among males (53.2%); most patients belonged to age group 20-29 years
      (86.5%), mean age was 25.56 years. The predominant route of transmission was
      parenteral (58.5%), followed by heterosexual transmission (40.1%). The mean CD4
      cell count was 246.20 cells/mm3, in over 41% of cases CD4 count ranging from 200
      to 499 cells/mm3. The mean HIV plasma viral load was 142,906 copies/ml. ALT
      levels varied between 10-323 IU/l, average 49.90 IU/l, over 65% of subjects
      having pathological levels. In 21.8% of the cases, total cholesterol was very
      high, and in 16.8% of the patients the serum triglyceride levels were below the
      reference range (160 mg %). CONCLUSIONS: Our results suggest that HIV-positive
      patients, chronic hepatitis B infection has a high incidence, especially in
      younger age groups and is correlated with significant degrees of
      immunosuppression.

PMID- 25076698
TI  - Pain modulation by curcumin and ascorbic acid in mice.
AB  - AIM: The present study aims to evaluate whether ascorbic acid (AA) and curcumin,
      two substances with redox properties, have similar effects on different models of
      pain in mice. MATERIALS AND METHODS: This study included a total of 28 mice that
      were divided into four groups. One group (AA) received intraperitoneally 500
      mg/kg b.w. AA for 21 days and the 2-nd group (curcumin) received 120 mg/kg b.w.
      curcumin by gastric gavage for two weeks. Other two groups serve as control and
      received vehicle in a dose--time manner similar to that of the treated groups.
      The pain models (oro-facial formalin induced pain, paw formalin induced pain and
      visceral pain) were performed 24 h after the last dose. RESULTS: When compared
      with control groups, curcumin significantly decreases pain perception in oro
      facial (p = 0.01 1-st phase, p = 0.002 2-nd phase) and paw formalin induced pain
      (p = 0.04 1-st and 2-nd phase) while AA stimulates pain perception in acid acetic
      induced visceral pain (p = 0.05) and increases oro-facial inflammatory pain
      induced by formalin ( p = 0.02) but demonstrates analgesic effects on paw
      formalin induced pain (p = 0.003 1-st phase, p = 0.01 2-nd phase). CONCLUSIONS:
      ROS production is important in pain modulation. Structures involved in the
      process of pain have different antioxidant defense capacities. Curcumin and AA
      are able to modulate pain perception, but beside their antioxidant capacities,
      there are other mechanisms involved.

PMID- 25076699
TI  - Determinants of inadequate weight gain in pregnancy.
AB  - AIM: The aim of the study was to explore the anthropometric maternal
      characteristics and prenatal care as determinants of pregnancy weight gain.
      MATERIAL AND METHODS: We conducted a cross-sectional study on a total of 400
      pregnant women admitted to Cuza-Voda Obstetrics and Gynecology Clinical Hospital,
      Iasi. Information on demographic characteristics, number of prenatal visits, and
      education on nutrition and food changes occurring during pregnancy were recorded
      in a structured questionnaire. Anthropometric parameters analyzed were
      pregestational BMI (body mass index) and weight gain during pregnancy. RESULTS:
      Weight gain was associated with pregestational BMI category. An increase in
      weight more than recommended occured more frequently in overweight (53.1%) and
      obese women (66.7%) (p < 0.001). Weight gain during pregnancy was related to area
      of residence, age, APCU (adequate prenatal care utilization) index. The
      multivariate analysis identified the following variables as significant
      determinants of pregnancy weight gain: inadequate prenatal care, BMI and changes
      in diet. CONCLUSIONS: Pregestational BMI and changes in diet during pregnancy
      identified as determinants of weight gain suggests that overweight and
      underweight women must carefully be counseled regarding recommendations for
      weight gain in pregnancy. Tracking diet changes is important to ensure that a
      weight gain lies within the guidelines recommendations.

PMID- 25076700
TI  - Amiodarone-induced thyroid dysfunction--clinical picture. Study on 215 cases.
AB  - AIM: The purpose of this study was to investigate the prevalence and the clinical
      evolutionary implications of thyroid damage in patients treated with amiodarone
      in the Cardiology Clinic of the "Sf. Spiridon" University Hospital of Iasi.
      MATERIAL AND METHODS: The study included a group of 215 patients, 90 men and 125
      women with ages between 35 and 87, hospitalized in the Cardiology Clinic between
      2004 and 2014, who received amiodarone treatment, in most cases for the
      prophylaxis of various arrhythmias, both supra-ventricular and ventricular.
      RESULTS: In 27.80% of the patients, the assessment of the thyroid function was
      imposed by the appearance of the clinical picture characteristic for hypo- and
      hyperthyroidism, and for 72.19% it was carried out as a routine examination.
      Amiodarone-induced hypothyroidism was clinically diagnosed in 20.85% of the
      patients. Hyperthyroidism occurring during treatment with Cordarone was found in
      6.95% of the patients. The confirmation of the diagnosis of amiodarone-induced
      thyroid dysfunction was based on hormonal dosages (TSH, FT4 and even FT3 in some
      cases), on the endocrinological clinical consultation and on the imaging study-
      i.e. thyroid echography. CONCLUSIONS: Amiodarone-induced thyroid dysfunction is
      relatively rare compared to the number of patients treated with this anti
      arrhythmic drug (27.8%) from the group under study. Thyroid dysfunction,
      regardless of the type (with hypo or hyper-function), represents a negative
      element in the evolution of patients with pre-existing heart diseases, not only
      by aggravating the clinical picture of the basic illness, but also by the
      necessity of permanently reviewing the therapeutic scheme imposed also by the
      association of thyroid dysfunction medication, according to case.

PMID- 25076701
TI  - The incidence of supraventricular arrhythmias in patients with essential arterial
      hypertension--clinical and evolutive correlations.
AB  - AIM OF THE STUDY: The analysis of supraventricular rhythm disorders encountered
      in hypertensive patients and the establishment of correlations with other
      associated risk factors, duration of hypertension, the evolution and prognosis.
      MATERIAL AND METHODS: The study included a group of 110 patients, 80 men and 30
      women, aged between 40 and 85, admitted in the 1st Cardiology Clinic during 2010
      2013, diagnosed with essential arterial hypertension second and third degree. For
      the detection of arrhythmic events surface 12-lead ECG and 24-hour Holter
      monitoring were used. RESULTS AND DISCUSSION: Supraventricular arrhythmias
      encountered in the patients of the group were: ESA (mostly isolated, but also
      doublets, atrial bigeminy), atrial fibrillation, atrial flutter, sinus
      tachycardia, sinus bradycardia. Some arrhythmias may be an expression of the
      excessive activation of the sympathetic nervous system or on the contrary, vagal
      predominance, (ex. sinus bradycardia). Part of the arrhythmias occurring in
      hypertensive patients are hypertensive heart disease expressions, others are due
      to associated risk factors (smoking, alcohol) and even medication administered.
      In some cases, rhythm disturbances disappear with the normalization of the blood
      pressure; however, most of the times, the specific combination of anti-arrhythmic
      medication with antihypertensive medication is required. CONCLUSIONS:
      Supraventricular arrhythmias are frequently found in hypertensive patients,
      especially in those with long-term, uncontrolled hypertension, with impact on the
      evolution, prognosis and therapeutic management.

PMID- 25076702
TI  - The efficacy of the Peginterferon treatment in chronic hepatitis HDV and
      compensate liver cirrhosis.
AB  - AIM: To evaluate the efficiency of the treatment with Peginterferon alfa 2a 180
      mcg/week, 48 weeks in patients with chronic hepatitis or compensated liver
      cirrhosis HDV and predictive factors of response to treatment. MATERIAL AND
      METHODS: Prospective study that enrolled 50 patients with chronic hepatitis or
      compensated cirrhosis HDV between the 1st of January 2011 - 3st of December 2011.
      The diagnosis of chronic HDV infection was made based on the presence of
      detectable anti HDV IgG antibodies and HDV-RNA. Patients were evaluated at
      baseline by CBC, liver function tests, HBV profile, HDV RNA, and by liver
      biopsy/Fibrotest for evaluating fibrosis and necroinflammatory activity. At 24
      weeks CBC (count blood cells), liver function tests, quantitative HBsAg and at 48
      and 72 weeks biochemical tests, HDV RNA, HBV DNA, quantitative HBsAg, were
      performed. Adverse reactions to the treatment were recorded. RESULTS: SVR
      (sustained virologic response) was recorded in 12 patients (24%) and biochemical
      response in 28 patients (56%). SVR was correlated with low-grade fibrosis, age,
      the aminotransferase value and the value of HBsAg at the beginning of the
      treatment. In week 48 HDV RNA was undetectable in 20 patients (40%). The therapy
      was well tolerated, except two patients for whom the discontinuation of the
      treatment was decided for severe exacerbation of cytolysis, respectively hepatic
      decompensation. CONCLUSIONS: In a representative group of patients, the treatment
      with Peginterferon once again proves its efficacy in treating chronic HDV.

PMID- 25076703
TI  - The importance of renal biopsy in the management of renal transplantation.
AB  - Renal biopsy remains the "gold standard" for the diagnosis of renal allograft
      dysfunction. The aim of our study was to highlight the importance of renal biopsy
      in the management of allograft dysfunction (early diagnosis and therapeutic
      approach). Our study included 23 renal allograft biopsies from 20 patients. This
      retrospective study analyzed the demographic and clinical data, histological
      results and the evolution of renal function under the immunosuppressive regimens.
      Conclusions: The most frequently encountered histopathological patterns were
      humoral rejection, interstitial fibrosis and chronic cellular rejection. Patients
      under continuous treatment with cyclosporine developed chronic cellular reject
      more frequently; on the opposite, patients under continuous treatment with
      tacrolimus developed chronic humoral reject more frequently.

PMID- 25076704
TI  - Possible progression of subacute lupus erythematosus--case report.
AB  - Subacute lupus erythematosus (SLE) is a specific form of lupus erythematosus
      characterized by prevalently cutaneous manifestations usually with a good
      prognosis. It is more common in patients aged 15 to 70 years, and there is a
      female predilection. This form accounts for 10% of all lupus erythematosus cases.
      We present the case of a 57-year-old male patient diagnosed at age 35 with
      chronic psoriasiform subacute lupus erythematosus, pathologically confirmed at
      the Iasi Dermatology Clinic. At the age of 54 years he had multiple ischemic
      strokes, followed by deterioration of general status, and at 56 years deep vein
      thrombosis in the right leg. The patient presented the erythematous-squamous
      lesions specific to psoriasiform SLE localized both on the upper third of the
      body and knees and associated with submucosal lesions of the lower lip, oral
      mucosa and appendages. The patient also presented hypo- and hyperpigmentated
      atrophic scar-like lesions. Laboratory tests performed during the last two
      admissions showed the presence of anti-ds DNA and antiphospholipid antibodies,
      inflammatory syndrome, and nitrogen retention syndrome. Treatment consisted of
      systemic and local dermatocorticoids and associated medication, emollient lotions
      and creams with SPF 50+, with slowly favorable progression. The peculiarity of
      the case lies in the chronic progression without significant systemic involvement
      for 19 years, and then in 2 years the antiphospholipid antibody syndrome and a
      shift to systemic lupus erythematosus to occur.

PMID- 25076705
TI  - Atypical presentation of systemic lupus erythematosus: parotitis and secondary
      Sjogren's syndrome. Case report.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by auto
      antibodies directed against self-antigens, immune complex formation and immune
      deregulations and may affect joints, skin, kidneys, heart, lungs, nervous system,
      and immune system. The onset can be variable and the symptoms can occur for many
      years. Parotitis as the initial manifestation of systemic lupus erythematosus
      (SLE) is a rare condition and can be associated with Sjogren's syndrome. In this
      article we present the case of a young patient who was diagnosed with Sjogren's
      syndrome retrospectively, after she met the criteria for SLE.

PMID- 25076706
TI  - Metabolic disorders in patients operated for pancreatic cancer.
AB  - Adenocarcinoma of the pancreas presents a major threat with a 5-years survival
      rate of 5%. Whipple pancreaticoduodenectomy (PD) is the standard procedure for
      cephalo-pancreatic neoplasm. After an extended resection and reconstruction of
      superior gastrointestinal tract the digestive physiology might be heavily
      disrupted. A literature review of metabolic alterations of patients who suffered
      a major pancreatic resection is performed, regarding micronutrients, lipid
      absorption and pancreatogenic diabetes. Long-term survivors following PD
      generally have a satisfactory nutritional status although with subclinical iron,
      vitamin D and selenium deficiency. These patients should be followed-up also
      regarding these micronutrients and properly dietary supplemented when necessary,
      also considering the increased life expectancy. Approximately 17-25% of patients
      will develop insulin-dependent diabetes but pancreatogenic diabetics have
      elevated levels of serum insulin and minimal or absent response to food intake,
      as opposed to a type I diabetics, where insulin serum is normal or elevated and
      there is an exaggerated response to ingestion of sugar.

PMID- 25076707
TI  - Malignancy and mortality of colorectal polyps.
AB  - OBJECTIVES: To evaluate the rate of morbidity and mortality associated with
      colorectal polyps after the next 8-years period of endoscopic polypectomy, in a
      high risk managed care population. MATERIAL AND METHOD: Cohorts of 77 subjects
      with benign neoplasms were identified with a colonoscopy in 1999. Three groups of
      subjects: benign neoplasms with polypectomy, benign neoplasms without
      polypectomy, and no neoplasms were evaluated. Five years recurrence rates (1999
      2004) of benign or new malignant colorectal neoplasms were identified: for the
      benign determined for the baseline benign neoplasms with polypectomy and no
      neoplasm groups neoplasm without polypectomy, only rates for malignancy were
      observed. Malignancy was evaluated with immunohistochemical p53 (tumor protein
      53) and PCNA (Proliferating Cell Nuclear Antigen) staining pattern. Over the next
      8 years 2004-2012 were evaluated the mortality and the recurrence rate of the
      benign polyps. RESULTS: 77 subjects were enrolled in our study; 71.4% were
      diagnosed with benign and 2.5% with malignant neoplasms. The 5-years cumulative
      incidence rates of malignant colorectal neoplasms in the no neoplasm (n = 20) and
      benign neoplasm groups (n = 55) were (n = 1) 5% and ( n = 10) 18.1%, respectively
      (p < 0.005). A lower 5-years malignancy rate was observed in benign neoplasms
      group with polypectomy (12%) compared to the benign neoplasm group without
      polypectomy (33.3%) (p < 0.05). The 8-years mortality rate was compared into
      benign recurrent polyps group and into malign group: the lower 8-years mortality
      rate was observed into benign polyp no neoplasm group (0%) and into benign
      recurrent polyps group (40%); the highest rate was observed into neoplasm group
      (100%). CONCLUSIONS: The high recurrence rate of benign colorectal neoplasms and
      a higher incidence of colorectal cancer in subjects at high risk-history of
      benign colorectal neoplasm-highlight a healthcare opportunity for surveillance
      and/or interventions to reduce the morbidity associated with colorectal
      neoplasms.

PMID- 25076708
TI  - Gonioscopic findings in patients with acute central/hemicentral retinal vein
      occlusions.
AB  - OBJECTIVES: To evaluate prospectively the gonioscopic findings and their changes
      during a 3-year follow-up period in patients with acute central/hemicentral
      retinal vein occlusions (C/HRVOs). MATERIAL AND METHODS: A comprehensive
      ophthalmological examination of both eyes including static and dynamic gonioscopy
      as well as ocular biometric measurements was performed in 57 patients with acute
      C/HRVOs. The angle configuration and its changes, the axial length of the globe,
      the anterior chamber depth and the corneal thickness were assessed. RESULTS: 12
      C/HRVO patients presented with narrow drainage angles (< or = 20 degrees) and 45
      had normal angles (> 20 degrees). Ocular globes with narrow angles had axial
      length and anterior chamber depth significantly smaller as well as cornea
      thickness significantly greater than the eyes with normal angles. Out of the 12
      patients with narrow angles, 6 cases had primary angle closure suspect (PACS), 5
      cases had primary angle closure (PAC) and one case primary angle closure glaucoma
      (PACG). 3 of the 6 PACS patients progressed to PAC in the 6th, 10th, and 18th
      months of the follow-up period. From the 8 PAC cases existing during the whole
      study interval, one case progressed to PACG during the 24th month of the folow-up
      interval. CONCLUSIONS: In the context of an ocular globe having its size
      significantly smaller than the normal eye, narrow angle may represent a local
      risk factor predisposing to C/HRVO. Intermittent episodes of angle closure may
      contribute by increasing the intraocular pressure to the occurrence of C/HRVO as
      well to the progression of the gonioscopic configuration from PACS to PAC and
      from PAC to PACG.

PMID- 25076709
TI  - Paraganglioma of the carotid body: case report.
AB  - With an incidence of 0.03% of all tumors, carotid body tumors (CBTs) are
      extremely rare. We present the case of a 63 year old female patient with an
      asymptomatic right sided neck mass of 3 cm diameter. Doppler ultrasound and
      contrast-enhanced CT confirmed the clinical suspicion of carotid body tumor. The
      patient underwent complete surgical excision of the Shamblin group II tumor and
      an adjacent lymph node, without preoperative embolization. The histopathological
      examination diagnosed a benign CBT. There were no postoperative complications at
      1 and 6 months follow-ups.

PMID- 25076711
TI  - Singular case of third ventricle metastasis of colorectal carcinoma--case report.
AB  - Third ventricle tumors are uncommon central nervous system lesions and unusual
      locations for metastatic colorectal cancer. We present a case of a 68 year old
      woman with a solitary 3rd ventricle lesion found on a computed tomography scan of
      the brain and the synchronous mass of the right colon. The aim in this case was
      local control of cerebral lesion with pathological diagnosis. Surgery was
      followed by a short-term good evolution but with sudden death.

PMID- 25076710
TI  - Split-thickness skin grafting in oncologic surgery of the limb--a case report.
AB  - Large excision of tumor soft tissues is often complicated by infections,
      seriously undermined blood supply and venous drainage, tendon exposure,
      functional impairment. We report the case of a 67 years old woman admitted for a
      sarcoma of the right forearm occurring 14 years after a modified radical
      mastectomy and adjuvant chemotherapy for carcinoma of the right breast. A wide
      excision of the lesion and split-thickness skin graft was performed with
      uneventful recovery and satisfactory healing of the graft tissue and functional
      aspect of the arm. In the last few decades, there has been a search for solutions
      in tissue repair without need for auto grafts, such as biological substitutes
      that could repair or improve the function of tissue. In case none of these
      products are available, auto graft is a good choice and it may be commonly used
      in the surgical treatment of postoperative soft tissues defects after oncologic
      surgery.

PMID- 25076712
TI  - Polycythemia vera syndrome--as a protrombothic state.
AB  - The aim of our study was to investigate whether the disorder of coagulation and
      fibrinolysis factors are mechanisms that contribute to the prothrombotic state in
      patients with polycythemia vera (PV) syndrome with or without cardiovascular
      disease (CVD), in order to identify the patients having high risk for thrombotic
      events. MATERIAL AND METHODS: The study comprises 20 patients divided in 2
      groups: 10 patients with PV syndrome (PV) and 10 patients with PV and
      cardiovascular diseases associated (PV+CVD). The patients were tested by
      determining three factors of coagulation profile: protein S, free fraction (PS),
      antithrombin III (AT III) and Protein C (PC). RESULTS: The level of the three
      parameters were found significantly modified in the both groups (p < 0.05);
      comparing the results between the two groups of patients, in the second group
      (PV+CVD) the level of the parameters were significantly lower than in the first
      group (PV). CONCLUSIONS: In PV syndrome the risk for thrombosis is also due to
      the changes in coagulation factors. Patients with associated cardiovascular
      disease, present a more severe risk for trombothic events, so regarding the
      disorder of coagulation factors, this represent a major mechanism implicated in
      the etiology of thrombosis in these categories of patients.

PMID- 25076713
TI  - Research on plasma and saliva levels of some bivalent cations in patients with
      chronic periodontitis (salivary cations in chronic periodontitis).
AB  - The purpose of this study was to determine whether chronic periodontitis can
      stand behind modifications in the salivary and blood concentration of some
      bivalent cations (Calcium, Magnesium, Zinc and Copper). For this purpose, we
      formed a group of 30 adult patients with clinically onset chronic periodontitis,
      and another one of 30 healthy patients as control. Both groups were free from
      acute oral pathology and general illnesses. The groups were divided again
      according to the habit of smoking. Total saliva samples were obtained as "first
      time in the morning", then weighed and processed. Cations were read on Atomic
      Absorption Spectrophotometer and by Ion Chromatography (Magnesium). The same
      patients were required to undergo laboratory blood tests for Calcium, Magnesium
      and Zinc. Data obtained was normalised, then statistically interpreted using two
      tailed heteroscedastic t-Student tests. Our data confirmed the existence of a
      connection between salivary calcium, magnesium, zinc and copper, and of blood
      magnesium, and chronic periodontitis. Salivary calcium and magnesium are affected
      by smoking.

PMID- 25076714
TI  - Epidemiological evaluation regarding the role of cystic fibrosis as a risk factor
      for child malnutrition.
AB  - Cystic fibrosis (CF) is the most common monogenic autosomal recessive disorder
      with progressive chronic evolution which is potentially lethal. Poor growth is a
      characteristic of children suffering from cystic fibrosis. A poor nutritional
      status is an independent risk factor for inadequate survival in cystic fibrosis
      and is associated with disease complications. The appropriate nutritional
      management is an important part of the treatment so that the patient with cystic
      fibrosis can achieve normal growth and development and maintain the best possible
      health status. A balanced diet supplemented with snacks high in fat and calories
      is necessary to increase the caloric intake in children with cystic fibrosis.
      Children with cystic fibrosis have higher caloric needs than healthy children of
      the same age and sex. Malnutrition in CF is multifactorial. Cystic fibrosis is a
      complex multisystem disorder affecting mainly the gastrointestinal tract and
      respiratory system. In the past, malnutrition was an inevitable consequence of
      disease progression, leading to poor growth, impaired respiratory muscle
      function, decreased exercise tolerance and immunological impairment. A positive
      association between body weight and height and survival has been widely reported.
      The energy requirements of patients with CF vary widely and generally increase
      with age and disease severity. Cystic fibrosis remains a paediatric disorder
      which is often underdiagnosed but which, if therapeutically managed properly (by
      means of drug therapy as well as by appropriate physiotherapy techniques), can
      lead to improved quality of life and, thus, to a bigger life expectancy.

PMID- 25076715
TI  - Epidemiological and pathological aspects of skin cancer in North East of Romania.
AB  - In the last years skin cancer has become the most frequent cancer in humans, with
      the majority made up of two tumors: malignant melanoma (MM) and non-melanoma skin
      cancer (NMSC). AIM: To provide for the first time in the North East region of
      Romania, descriptive epidemiological data of melanoma and non-melanoma skin
      cancers. MATERIAL AND METHODS: We undertook a retrospective study over a five
      year period on the most frequent forms of skin cancer, basal cell carcinoma
      (BCC), squamous cell carcinoma (SCC) and MM, which included a total number of
      1231 patients, hospitalized and treated in the Plastic Surgery Department of "St.
      Spiridon" Emergency Clinical Hospital, Iasi from 2008 until 2012. Results: BCC
      was diagnosed in a total of 675 patients, representing 54.9%. SCC was found in
      217 patients, representing 17.6% and melanoma was diagnosed in 119 cases, a
      percent of 9.7% of the total number. The predominance of cutaneous malignancies
      waried with age, major site distribution was face and neck for BCC and SCC and
      the trunk for MM. RESULTS: This article describes the most common forms of skin
      cancer in our region, BCC (almost 55%), SCC (17.6%), and less in number MM (near
      to 10%); these results are similar to those published abroad in the last years.
      CONCLUSIONS: Future more elaborate interventional studies are necessary to
      identify the main risk factors in order to design the best preventive methods
      and, according to the skin cancer trend to specify the needs for dermatology
      network in our country.

PMID- 25076716
TI  - Epidemiology of B/C virus infection hepatitis in the Northern Moldavian
      correctional facilities risk factors.
AB  - AIM: To identify the specific risk factors for chronic hepatitis B/C virus
      infections in the correctional system in Moldova (Romania). MATERIAL AND METHODS:
      The study included 533 subjects imprisoned in three correctional facilities
      located in the Northern region of Moldova. The subjects were divided into 2
      groups: HBV/HBC group--108; Control group--425. RESULTS: The risk factor for
      transfusion-contracted HBV/HCV was 3.73; the empirical treatment of the HBV/HBC
      group resulted in a relative infection risk of 2.62; syringe sharing in the
      HBV/HBC group accounted for a risk factor of over 4 (OR = 4.33); tattooing
      induced a relative risk factor of 1.25, and piercing was a risk factor of
      approximately 2 (OR = 1.97); sharing personal care items represented a risk
      factor of over 2 (OR = 2.02). Injection drugs induced a relative risk of over 4
      (OR = 4.33). In the HBV/HCV group, self-aggression represented a risk factor of
      1.65. CONCLUSIONS: Prison environment, by its specific and nonspecific
      contamination modalities (shared with the rest of the population but more common)
      causes that inmates to be 2-4 times more exposed to hepatitis B/C infection.

PMID- 25076717
TI  - Clinical and epidemiological assessment of the incidence of arterial hypertension
      in a permanent medical center.
AB  - The present study shows the results of monitoring, evaluation and prediction of
      health status in a patient group with hypertension (HTN) seeking care in a
      permanent medical center. MATERIALS AND METHODS: The study evaluated 144 patients
      registered at the Permanent Medical Center of the Plugari village, Iasi County,
      who were diagnosed with HTN between 2011 and 2013. The study group included 80
      male patients with an average age of 51.25 years with a diagnosis of essential
      hypertension (EHTN) stage I, II or III and 64 female patients (group II), with an
      average age of 48.4 years. RESULTS: 44 patients (30.55% of the total number of
      patients) were diagnosed with HTN stage I, of whom 27 were female (61.36%) and 17
      were male (38.64%); 69 patients (47.93%) had HTN stage II, of whom 21 were female
      (30.43%) and 48 were male (69.57%), and 31 patients (21.52%) had HTN stage III,
      of whom 16 were female (51.61%) and 15 were male (48.39%). CONCLUSIONS: Patients
      at high risk for HTN and those with mild and moderate clinical forms were
      surveyed and were early treated. Economic and social benefits were achieved due
      to lower hospitalization costs, fewer days of temporary disability and reduced
      medical retirements. In our study groups, HTA had a higher prevalence, especially
      in men.

PMID- 25076718
TI  - Epidemiological and laboratory features of chronic hepatitis B cases in the
      interval 2010-2013.
AB  - HBV virus infection is an important public health problem because of its huge
      transmission potential, and severe evolution to cirrhosis or liver cancer. AIM:
      Analysis of the epidemiological and laboratory features of chronic hepatitis B
      virus infection. MATERIAL AND METHODS: The patients with chronic hepatitis B
      admitted to the "Sf. Parascheva" University Hospital for Infectious Diseases in
      the interval: January 1st, 2010 - December 31st were analyzed. RESULTS: Patients
      age was 18 to 66 years with a prevalence of middle-aged males. Most patients came
      from urban areas. Alanine aminotransferase (ALAT) levels were elevated, without
      significant differences between HBeAg-positive and HBeAg-negative patients, the
      elevated ALAT levels being associated with the increased prevalence of fibrosis.
      HBeAg-positive patients had viral loads above the threshold of 2,000/l in 34
      cases (89.5%), and below 2,000 IU/l in only 10.5% of cases, and the majority
      (88%) of HBeAg-negative patients presented high viral load levels. The prevalence
      of stage F2-F4 liver fibrosis was 63.4% in the HBeAg-negative patients with
      viremia > 25,000 IU/l compared to 55.2% in the HBeAg-positive patients. The
      correlation between the level of viral load and fibrosis shows that there are
      significant differences between viremia and the status of HBeAg-positive or
      negative patients. Increased viral load was correlated with increasing prevalence
      of fibrosis, significant in HBeAg-negative patients, and the increasing fibrosis
      prevalence was correlated with low viral load. CONCLUSIONS: The correlation
      between viral load and fibrosis shows that there are significant differences
      between viral load and the status of HBAg-positive or negative patients.

PMID- 25076719
TI  - Using ArcGIS software in the pre-hospital emergency medical system.
AB  - AIM: To measure the accessibility to healtcare services in order to reveal their
      quality and to improve the overall coverage, continuity and other features.
      MATERIAL AND METHODS: We used the software ESRI Arc GIS 9.3, the Network Analyst
      function and data provided by Ambulance Service of Iasi (A.S.I.) with emergencies
      statistics for the first four months of 2012, processed by Microsoft Office Excel
      2010. As examples, we chose "St. Maria" Children's Emergency Hospital and "St.
      Spiridon" Emergency Hospital. RESULTS: ArcGIS Network Analyst finds the best
      route to get from one location to another or a route that includes multiple
      locations. Each route is characterized by three stops. The starting point is
      always the office of Ambulance Service of Iasi (A.S.I.), a second stop at the
      case address and the third to the hospital unit chosen according to the patient's
      diagnosis and age. Spatial distribution of emergency cases for the first four
      months of 2012 in these two examples is one unequable, with higher concentrations
      in districts located in two areas of the city. CONCLUSIONS: The presented
      examples highlight the poor coverage of healthcare services for the population of
      Iasi, Romania, especially the South-West area and its vulnerability in situations
      of emergency. Implementing such a broad project would lead to more complex
      analyses that would improve the situation of pre-hospital emergency medical
      services, with final goal to deserve the population, improve the quality of
      healthcare and develop the interdisciplinary relationships.

PMID- 25076720
TI  - Clinical-epidemiological study on advanced non-small cell lung cancer.
AB  - AIM: To assess the clinical and epidemiological features of all three main
      histological types of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:
      The study included 34 patients with NSCLC admitted to specialized units of the
      Iasi Regional Cancer Institute (IRCI) in the interval May 2012 - May 2014. Data
      were collected electronically based on a clinical-epidemiological survey form.
      The obtained data were then processed and interpreted by statistical-mathematical
      methods using the correlation index (significant at p < or = 0.05 and highly
      significant at p < 0.005), chi-square and Y tests. Data were analyzed using SPSS
      13.0 (SPSS Inc. Chicago, Illinois, USA). RESULTS: Most NSCLC patients were aged
      56-71 years, the Pearson correlation index between age and diagnosis being p =
      0.01. Sex difference was highly significant (p = < 0.001) and so was the
      relationship between heavy smoking and age groups. Most cases were
      histogenetically classified as adenocarcinomas (22%). Four patients (21%) were in
      stage IIIA NSCLC, 4 (21%) IIIB, 9 (47.3%) IV, and 15 (79%) unspecified stage. All
      patients received primary chemotherapy. Single or associated complications
      included anemia and other hematologic disorders (26-74.6%), respiratory failure,
      hemoptysis, cachexia, atelectasis, etc. Surgery was performed in 5 (14.7%) stage
      IIIA NSCLC patients. CONCLUSIONS: NSCLC showed a highly significant predominance
      in the age groups 56-71 years, and the most common histologic type was
      adenocarcinoma. All patients received primary chemotherapy, and patients with
      stage IIIA underwent surgery. Anemia and other hematologic disorders were the
      most common complications.

PMID- 25076721
TI  - Influence of antibiotic therapy prior to admission on the efficacy of classical
      methods for the diagnosis of meningococcal disease.
AB  - AIM: To assess the influence of preadmission antibiotic therapy on the results of
      the classical methods for bacteriological confirmation of meningococcal disease
      (MD). MATERIAL AND METHODS: Retrospective study of the MD cases diagnosed in the
      "St. Parascheva" Universitary Clinical Infectious Diseases Iasi between 1994 and
      2011. RESULTS: The etiological diagnosis was made by identifying the
      meningococcus in the CSF (cerebrospinal fluid) in 71.9% of the 323 patients and
      by blood culture in 8%. Preadmission antibiotic therapy received 39% of the
      patients, thus the sensitivity of test was significantly reduced: direct
      examination from 64.6% to 43.2% (p < 0.001), cultures from 55.9% to 27.2% (p <
      0.001), and latex-agglutination from 84.6% to 58.8% (p = 0.003). The rate of
      positive CSF decreased from 82.1% to 56% (p < 0.001). Preadmission antibiotic
      therapy significantly increased the ratio of cases in which meningococcus was not
      detected in CSF by any of the classical methods (44% compared to 17.9% in the
      cases without prior treatment). The proportion of cases in which meningococcal
      isolation was done by two methods decreased from 38.5% to 19.2%, and of those by
      all three methods from 16.9% to 5.6% (p < 0.001). Preadmission antibiotic therapy
      also decreased the rate of positive blood cultures from 14.7% to 3.5% (Fisher's
      exact test, p = 0.009). CONCLUSIONS: Antibiotic treatment prior to admission
      significantly decreases the percentage of patients with MD in which meningococcal
      isolation can be done; this requires the use of a more sensitive diagnosis method
      (ex. qPCR).

PMID- 25076722
TI  - Personality profiles and risk diet behaviors--a case-control study on teenagers
      from Timis County, Romania.
AB  - In the study we conducted we aimed at investigating the relation between
      personality profiles and risk diet behaviors in teenagers. This study was a case
      control one and we applied 2 questionnaires (Freiburg Personality Inventory--FPI
      with 212 items) and CORT 2004 (items Q94-Q116 of diet behavior) on a sample of
      2908 teenagers (51.5% girls and 48.5% boys). Cronbach's alpha index was 0.802 for
      FPI and 0.730 for items Q101-Q109 of CORT. Personality profiles were built by an
      Excel 2003 Program. Statistical analysis was realized with SPSS 16 program
      applying Chi square (chi2) and gamma (gamma) correlation. Personality features of
      teenagers with high and without risk diet behavior were analyzed. Results
      obtained: personality profiles and statistical results indicated the existence of
      a significant statistical difference of aggressiveness and domination between
      teenagers with high and no consumption of butter and/or lard (Q103) (chi2 =
      6.872, Sig. 0.032 and chi2 = 6.922, Sig. 0.031 respectively), of juices from the
      market (Q106) (chi2 = 9.055, Sig. 0.011 and chi2 = 14.571, Sig. 0.001
      respectively). Aggressiveness correlated with consumption of fried potatoes
      (Q109) (chi2 = 6.144, Sig. 0.046) too. Correlation gamma indicated direct
      proportional relations of aggressiveness with: Q103 (gamma = 0.215, Sig. 0.017),
      Q106 (gamma = 0.224, Sig. 0.004), Q109 (gamma = 0.242, Sig. 0.012); and of
      domination with: Q103 (gamma = 0.234, Sig. 0.008), Q106 (gamma = 0.073, Sig.
      0.000). In conclusion, there is a direct proportional relation between
      consumption of: butter/lard, juices from the market and teenagers'
      aggressiveness, domination; and a similar relation between consumption of fried
      potatoes and aggressiveness.

PMID- 25076723
TI  - Predictors of postsurgical stress among cardiac patients.
AB  - AIM: To explore the role of stress vulnerability, dispositional optimism, fears
      of surgery and negative affective disposition in prediction of postsurgical
      stress among cardiac patients who underwent heart surgery. MATERIAL AND METHODS:
      The sample included 60 cardiac patients (39 males and 21 females, aged 58.50 +/-
      10.97 years). All patients completed two sets of standardized questionnaires.
      Before surgical intervention, stress vulnerability, dispositional optimism and
      negative affective disposition were measured with N6-Scale (from NEO Personality
      Inventory-Revised Form), Life Orientation Test-Revised Form and Mental Health
      Index-5, respectively. Fear of surgery among patients was measured with an 8-item
      questionnaire designed for the current study. After intervention, patients
      completed a short postsurgical data form along with the Perceived Stress Scale.
      RESULTS: There was no significant difference in postsurgical stress between the
      female and male cardiac patients (t = 0.96; p = 0.34). A similar result was
      obtained when the presence/absence of postsurgical complications was considered
      as an independent variable (t = 1.30; p = 0.19). As expected, a higher level of
      postsurgical stress was associated with higher stress vulnerability, surgery
      related fear, negative affective disposition, and with a lower dispositional
      optimism score. Moreover, stress vulnerability and negative affective disposition
      were significant predictors of postsurgical stress. CONCLUSIONS: Cardiac patients
      who are prone to stress and negative affective disposition are also at higher
      risk for postsurgical stress. On its turn, this psychological condition
      interferes with time and quality of postsurgical recovery. A careful assessment
      of psychological condition along with counseling before surgical intervention is
      needed in order to reduce the risk of postsurgical stress and improve medical
      recovery in cardiac patients.

PMID- 25076724
TI  - The evaluation of preoperative nutritional status in patients undergoing thoracic
      surgery.
AB  - AIM: The aim of this study was to assess the preoperative nutritional status of
      patients undergoing thoracic surgery using different nutritional tools. MATERIAL
      AND METHOD: . We conducted a prospective study on a sample of 43 thoracic
      patients, including 23 with neoplasms and 20 with non-neoplastic pathology who
      underwent thoracic surgery procedures between July-September 2011, in the
      Thoracic Surgery Clinic in Iasi. Weight and height were measured and body mass
      index (BMI) was calculated. WHO classification for BMI categories was used.
      Preoperative serum level of transthyretin (TTR) and demographic data (gender,
      age) were also assessed. All patients were examined by the Subjective Global
      Assessment (SGA) and the Nutritional Risk Screening 2002 (NRS 2002). RESULTS:
      After performing SGA, 67.9% of the patients were well-nourished, 21.4% were
      moderately or suspected of being malnourished and 10.7% were severely
      malnourished. The level of TTR was significantly lower in the moderately or
      severely malnourished group, compared to those considered well-nourished.
      According to NRS-2002, 42.9% of the patients were considered at nutritional risk.
      The level of TTR of these patients was lower than the level of TTR of the
      patients without nutritional risk, but without statistical significance.
      CONCLUSIONS: Subjective Global Assessment (SGA) and the Nutritional Risk
      Screening 2002 (NRS 2002) are useful in identifying patients with nutritional
      risk, so that appropriate nutritional management could be initialised even before
      surgery.

PMID- 25076725
TI  - The importance of control elements in dental office management.
AB  - In the current economic situation statistical indicators suggest a decline in
      global and national dental services market under increased competition. Hence, a
      cost-effective and strengthening market position. Thus it is recommended the
      office management to focus on retention and follow active patients and to create
      a system of quality control maneuvers. In order to achieve these objectives we
      must monitor certain elements of medical control, economic, management and
      promotion.

PMID- 25076726
TI  - Dental patients' attitudes towards infection control.
AB  - The level of the patients' education for health is increasing as their concern
      for protection during the medical treatment. The aim of this study was to assess
      the attitudes of the dental patients towards infection control protocols in the
      dental office. MATERIAL AND METHODS: A questionnaire-based study was initiated
      including 210 patients aged between 16 and 68 years. Data was processed using
      SPSS 14.0 and analyzed by age, gender and level of education. RESULTS: 82.6% of
      the patients trust the medical staff to protect them against the spread of
      infection. Female subjects are twice as interested in the follow up of infection
      control procedures as males (53.4% respectively 25.2%). The diseases considered
      by the patients as presenting a high risk of transmission during dental treatment
      are: hepatitis B, HIV infection, hepatitis C, tuberculosis and hepatitis A. The
      subjects require the dentist to wear rubber gloves (89.2%), masks (61.5%) and
      glasses (45.5%). CONCLUSION: The involvement of the dental patients in their own
      treatment is essential in order to increase the safety and quality of the dental
      procedures.

PMID- 25076727
TI  - Echinocandins--new antifungal agents.
AB  - Over the past 10-15 years, the number of clinically available antifungal agents
      has increased substantially, due to rise in the number of invasive fungal
      infections, which are a real problem for specialists. Echinocandins are the new
      class of antifungal agents available for clinical use. This class comprises over
      20 natural echinocandins and several semisynthetic ones. Natural echinocandins
      are not of clinical utility due to their toxicity and low water-solubility (which
      does not allow obtaining parenteral pharmaceutical forms), although they have
      good antifungal activity against Candida species. Consequently, semisynthetic
      echinocandins with minimal toxicity, good antifungal activity and high water
      solubility were obtained. All echinocandins inhibit beta-1,3-glucan-synthase, an
      essential component of the fungal cell wall. Echinocandins exhibit potent
      antifungal activity against key pathogenic fungi, including Candida species,
      Aspergillus species and Pneumocystis carinii. The available echinocandins lack in
      vitro activity against Cryptococcus neoformans. The semisynthetic echinocandins
      have great advantages, among which low toxicity, fast antifungal activity,
      favorable pharmacokinetics that allow once-daily administration. The
      echinocandins recently available for clinical use are: caspofungin, micafungin
      and anidulafungin.

PMID- 25076728
TI  - Screening of antibacterial effects of anise essential oil alone and in
      combination with conventional antibiotics against Streptococcus pneumoniae
      clinical isolates.
AB  - AIM: This study aimed to investigate the effects of anise essential oil alone and
      in combination with conventional antibiotics (amoxicillin, ciprofloxacin) against
      Streptococcus pneumoniae clinical isolates. MATERIAL AND METHODs: Anise essential
      oil (AEO) was isolated by hydrodistillation from dried powdered fruits. Its
      chemical composition was investigated by GC-MS and GC-FID. Broth dilution assay
      was used to evaluate the antibacterial effects of anise essential oil. The
      interactions with antibiotics were studied by the checkerboard assay. RESULTS:
      Trans-anethole (90.18%) was identified as major constituent in anise essential
      oil. Almost all combinations AEO-amoxicillin and AEO-ciprofloxacin showed
      indifferent interactions (1 < FIC index < or = 2). Positive interactions
      (addition and weak synergism) were found only for four combinations AEO
      amoxicillin (FIC index = 1,0.62, 0.75 and 0.5) and one combination AEO
      ciprofloxacin (FIC index = 0.62). CONCLUSIONS: Herbal products containing anise
      essential oil may be used as expectorants in combination with amoxicillin or
      ciprofloxacin in Streptococcus pneumoniae infections without diminishing
      antibiotic efficacy.

PMID- 25076729
TI  - In vitro screening of Crataegus succulenta extracts for free radical scavenging
      and 15-lipoxygenase inhibitory activities.
AB  - Crataegus succulenta Schrad. ex Link is widely spread in North America. A
      literature survey revealed no studies on the chemical composition and biological
      effects of this species. AIM: The aim of the present study was to investigate the
      phenolic content, free radical scavenging and 15-lipoxygenase inhibitory effects
      of Crataegus succulenta leaf and flower extracts. MATERIAL AND METHODS: Total
      phenolic, flavonoid and proanthocyanidin contents were quantified by
      spectrophotometric methods. Both extracts were evaluated for their ability to
      scavenge DPPH, superoxide anion and hydroxyl radicals and to inhibit 15
      lipoxygenase activity. RESULTS: There were noticed no striking differences in the
      total phenolic, flavonoid and proanthocyanidin contents between leaf and flower
      extracts. Both extracts showed similar 15-lipoxygenase inhibitory effects. Flower
      extract scavenged more effectively DPPH and superoxide radicals while leave
      extract was more active against hydroxyl radical. In superoxide anion radical
      scavenging assay, both extracts were more active than (+)-catechin. In hydroxyl
      radical scavenging and 15-lipoxygenase inhibition assays, the extracts were only
      4-5 times less active than (+)-catechin. CONCLUSIONS: The high antioxidant
      potential of Crataegus succulenta extracts suggest a possible use as ingredients
      in functional foods for the prevention of oxidative stress-related diseases.

PMID- 25076730
TI  - Polyphenol-rich extract from Pinus sylvestris L. bark--chemical and antitumor
      studies.
AB  - Pinus sylvestris L. is a very important timber tree in Romania, the bark being
      the main waste from the wood processing. AIM: The aim of this study was to
      investigate the chemical composition and antitumor effects against HeLa cells of
      a polyphenol-rich extract from Pinus sylvestris L. bark. MATERIAL AND METHODS:
      The polyphenolic content and profile were analyzed by means of spectrophotometry
      and RP-HPLC-UV/ESI-MS in the negative ion mode. The antitumor activity was
      investigated using two in vitro assays: MTT and flow cytometric apoptosis assays.
      RESULTS: Pine bark extract contained a high total phenolic content (48.16 +/-
      0.29%). RP-HPLC-UV/ESI-MS analysis allowed the identification of taxifolin, a
      taxifolin-hexoside and several procyanidins (two monomers, three dimers and three
      trimers). At 200 microg/mL, pine bark extract exhibited a high cytotoxicity
      against HeLa cells (82.10 +/- 1.95%). Flow cytometry revealed the ability of pine
      bark extract to induce apoptosis: 71.97 +/- 0.96% apoptotic cells were determined
      in HeLa cells after a 48 h incubation with pine bark extract (200 microg/mL).
      CONCLUSIONS: The ability of pine bark extract to reduce viability and induce
      apoptosis in HeLa cells suggests the presence of compounds with antitumor
      properties and encourages further studies for their isolation and
      characterization.

PMID- 25076731
TI  - Spectrophotometric method for estimation of bisoprolol fumarate in tablets.
AB  - Bisoprolol fumarate is prescribed for the treatment of hypertension and angina
      pectoris. AIM: The purpose of this study was to develop a simple, sensitive,
      accurate, and reproducible method for estimation of bisoprolol fumarate in
      tablets. MATERIAL AND METHODS: The proposed method was based on a yellow colored
      complex formed with tropaeolin 00, extractable in dichloromethane with maximum
      absorbance at 412 nm. The method was validated statistically. RESULTS: The
      linearity domain was observed in the concentration of 5-30 microg/ml. The
      recovery studies confirmed the accuracy of the proposed method. CONCLUSIONS: The
      proposed method can be applied for the routine analysis of bisoprolol from
      formulations.

PMID- 25076732
TI  - Antioxidant activities and phenolic contents of extracts from Glinus
      oppositifolius aerial parts.
AB  - In Malian traditional medicine, aerial parts of Glinus oppositifolius are used in
      the treatment of many disorders, particularly inflammations and joint pains. AIM:
      The present study was initiated to investigate the antioxidant potential of
      Glinus oppositifolius. MATERIAL AND METHODS: Aqueous and ethanol extracts were
      prepared from the dried aerial parts. Both extracts were examined for the
      phenolic content and antioxidant activity. Total phenolic content was quantified
      by Folin-Ciocalteu method. Antioxidant activity was studied in vitro by
      evaluating the ability to scavenge different free radicals (ABTS, superoxide and
      hydroxyl radicals, nitric oxide) and to chelate ferrous ions. RESULTS: Aqueous
      extract was found to contain a higher level of total phenols than ethanol extract
      (1.27 +/- 0.04 vs. 0.94 +/- 0.05 g GAE/100 g extract). Both extracts lacked the
      ability to scavenge superoxide anion radical but scavenged ABTS and hydroxyl
      radicals, nitric oxide and chelated ferrous ions in a concentration-dependent
      manner. According to the EC50 values, aqueous extract showed stronger antioxidant
      effects than ethanol extract (174.32 +/- 1.49 vs. 276.76 +/- 1.52 microg/mL in
      ABTS radical cation scavenging assay, 119.91 +/- 1.70 vs. 240.57 +/- 0.97
      microg/mL in nitric oxide scavenging assay, 1.99 +/- 0.01 vs. 6.54 +/- 0.08 mg/mL
      in ferrous ion chelating assay). In hydroxyl radical scavenging assay, aqueous
      extract had an EC50 value of 0.86 +/- 0.00 mg/mL while the EC50 value of ethanol
      extract was higher than the highest concentration that was tested (3.75 mg/mL).
      CONCLUSIONS: Our results clearly indicate the antioxidant potential of Glinus
      oppositifolius aerial parts and suggest that the antiinflammatory activity might
      be partly related to the antioxidant potential.

PMID- 25076733
TI  - Taguchi method for partial differential equations with application in tumor
      growth.
AB  - The growth of tumors is a highly complex process. To describe this process,
      mathematical models are needed. A variety of partial differential mathematical
      models for tumor growth have been developed and studied. Most of those models are
      based on the reaction-diffusion equations and mass conservation law. A variety of
      modeling strategies have been developed, each focusing on tumor growth. MATERIAL
      AND METHODS: Systems of time-dependent partial differential equations occur in
      many branches of applied mathematics. The vast majority of mathematical models in
      tumor growth are formulated in terms of partial differential equations. We
      propose a mathematical model for the interactions between these three cancer cell
      populations. The Taguchi methods are widely used by quality engineering
      scientists to compare the effects of multiple variables, together with their
      interactions, with a simple and manageable experimental design. In Taguchi's
      design of experiments, variation is more interesting to study than the average.
      RESULTS: First, Taguchi methods are utilized to search for the significant
      factors and the optimal level combination of parameters. Except the three
      parameters levels, other factors levels other factors levels would not be
      considered. Second, cutting parameters namely, cutting speed, depth of cut, and
      feed rate are designed using the Taguchi method. Finally, the adequacy of the
      developed mathematical model is proved by ANOVA. According to the results of
      ANOVA, since the percentage contribution of the combined error is as small.
      CONCLUSIONS: Many mathematical models can be quantitatively characterized by
      partial differential equations. The use of MATLAB and Taguchi method in this
      article illustrates the important role of informatics in research in mathematical
      modeling. The study of tumor growth cells is an exciting and important topic in
      cancer research and will profit considerably from theoretical input. Interpret
      these results to be a permanent collaboration between math's and medical
      oncologists.

PMID- 25076734
TI  - Looking forward. ACS speaks for surgeons and surgical patients to influence
      health policy.

PMID- 25076735
TI  - Surgeons see future applications for Google Glass.

PMID- 25076736
TI  - The ACS Accredited Education Institutes Fellowship Program: training leaders in
      simulation-based education.

PMID- 25076737
TI  - Distinguishing QI projects from human subjects research: ethical and practical
      considerations.

PMID- 25076738
TI  - SurgeonsVoice: your patients, your profession your voice.

PMID- 25076739
TI  - The ICD-10 delay.

PMID- 25076740
TI  - ACS rural listserv: an "underdog" success story.

PMID- 25076741
TI  - SLN surgery for clinically node-positive breast cancer patients treated with
      neoadjuvant therapy.

PMID- 25076742
TI  - Franklin H. Martin, MD, FACS: gynecologic surgeon.

PMID- 25076743
TI  - Renewed awareness of infection control during surgery.

PMID- 25076744
TI  - NTDB data points: To protect your children, keep your pool safe.

PMID- 25076745
TI  - Outstanding Achievement Award granted to 74 CoC facilities.

PMID- 25076748
TI  - First Carlos Pellegrini Traveling Fellow reports on experience.

PMID- 25076749
TI  - Inaugural Murray F. Brennan, MD, FACS, International Guest Scholar provides
      report.

PMID- 25076750
TI  - 2013 International Surgical Education Scholar reports on experience in North
      America.

PMID- 25076751
TI  - [Nikolai Pavlovich Kravkov--life devoted to pharmacology].

PMID- 25076752
TI  - [Assessment of afobazole effects on diazepam withdrawal-induced anxiety in rats].
AB  - Long-term administration of benzodiazepines is known to be associated with drug
      dependence. The aim of the present work was to investigate the effects of non
      benzodiazepine anxiolytic afobazole in the treatment of benzodiazepine withdrawal
      syndrome. Male outbred rats were treated with either diazepam (4.0 mg/kg, i.p.)
      or vehicle for 30 days and then abruptly withdrawn for 48 h. Animals were tested
      in the elevated plus maze test. In addition, neurochemical shifts were evaluated
      in the selected brain structures (striatum, hippocampus, hypothalamus, and
      frontal cortex) during diazepam withdrawal. Withdrawn animals made fewer entries
      and spent less time on the open arms than did vehicle-treated rats and
      demonstrated a decrease in the dopamine level in striatum as compared with
      vehicle and diazepam-treated ones. Afobazole (5.0 mg/kg, i.p.) effectively (i)
      ameliorated withdrawal-induced anxiety, returning behavioral pattern in the
      elevated plus maze test up to levels comparable to that in vehicle-treated
      animals, and (ii) increased withdrawal-reduced dopamine level (+23.8%, p < 0.05)
      in striatum. It is suggested that afobazole, due to its multitarget receptor
      action, can be useful in the diazepam withdrawal-induced anxiety blockade through
      modulation of dopaminergic system activity.

PMID- 25076753
TI  - [Effects of 8-OH-DPAT and m-CPP on depression-like behavior in prenatally
      stressed ovariectomized rats treated with low dose of 17beta-estradiol].
AB  - The present work was aimed at a comparative estimation of the effect of
      stimulation of 5-HTIA and 5-HT(2B/2C) receptors on depression-like behavior in
      adult ovariectomized (estrogen-deficient) female offspring from prenatally
      stressed (PS) mothers. PS ovariectomized female rats were treated for 14 days of
      with the vehicle, a low dose of 17beta-estradiol (5.0 microg/rat, s.c.), 5-HT(1A)
      receptor agonist 8-OH-DPAT (0.05 mg/kg), 5-HT(2B2C) receptor agonist m-CPP (0.5
      mg/kg), 8-OH-DPAT plus 17beta-estradiol, or m-CPP plus 17beta-estradiol. Then,
      the behavior of PS ovariectomized female rats was studied in the forced swimming
      (Porsolt) test and the open-field test. It was established that 8-OH-DPAT
      administered alone or in a combination with a low dose of 17beta-estradiol
      produced an antidepressant-like effect in the forced swimming test as compared to
      the untreated control PS ovariectomized offspring. Application of these drugs in
      PS ovariectomized offspring led to decreased frequency of rearing, exploratory
      behavior, and grooming in the open field test. The m-CPP treatment also resulted
      in an antidepressant-like effect in PS ovariectomized offspring in the forced
      swimming test. However, co-administration of m-CPP with a low dose of 17beta
      estradiol to PS ovariectomized offspring increased the level of depression, thus
      producing pro-depressant effect in the forced swimming test.

PMID- 25076754
TI  - [Anxiolytic and antidepressant effects of 3-oxypiridine and succinic acid
      derivatives in the acute phase of alloxan-induced diabetes in rats].
AB  - The effect of derivatives of 3-oxypyridine and succinic acid (emoxypine,
      reamberin, and mexidol) on the manifestations of anxiety (according to the
      criteria of behavior in elevated cross plus maze test) depression (according to
      the criterian of immobility in the Porsolt test) in the acute phase of alloxan
      diabetes (96 h after alloxan administration) has been studied in rats. The
      effectiveness of emoxypine, reamberin, and mexidol was compared with that of
      alpha-lipoic acid (etalon treatment of diabetic neuropathy). It was established
      that a single administration of 3-oxypyridine and succinic acid derivatives in
      doses equivalent to the therapeutic range for humans corrected anxio-depressive
      disorders in the acute phase of alloxan diabetes, while being not inferior to
      alpha-lipoic acid with respect to the intensity of anxiolytic and antidepressant
      action. The correction of affective disorders by emoxypine, reamberin and mexidol
      did not depend on their effect on hyperglycemia in the acute phase of alloxan
      diabetes. The most pronounced anxiolytic action was observed upon the
      administration of emoxypine, while the most pronounced antidepressant effect was
      observed upon the administration of mexidol.

PMID- 25076755
TI  - [Influence of unilayered and multilayered liposomes containing fatty-acid complex
      Bien upon phagocyte activity in rat alveolar macrophages].
AB  - The phagocyte activity of rat alveolar macrophages and their primary culture
      under the interaction with liposomes containing unsaturated fatty acid complex
      Bien has been studied in vitro. Quantitative dependence of the phagocyte number
      and phagocyte factor on the liposomal Bien concentration were estimated.
      Comparative analysis of the effects of multilayered and unilayered liposomes with
      Bien upon cell suspension has been carried out.

PMID- 25076756
TI  - [Features of bemithyl pharmacokinetics upon inhalation administration].
AB  - A comparative study of bemithyl pharmacokinetics was carried out upon its
      inhalation, intragastric and intravenous administration. The main drug
      metabolites were identified and the pharmacokinetic parameters were calculated.
      The obtained results suggest that the inhalation administration of bemithyl is a
      promising replacement for oral administration, which is related to high
      bioavailability of the drug and the absence of the effect of "first pass" through
      the liver.

PMID- 25076757
TI  - [Identification of histochrome metabolism products in urine for studying drug
      pharmacokinetics].
AB  - Histochrome is the medicinal form of echinochrome (2,3,5,6,8-pentahydroxy-7-ethyl
      1,4-naphthoquinone). The drug pharmacodynamics and its relationship with
      metabolism, which was revealed in previous investigations, predetermined the aim
      of this work: to study excretion of echinochrome and its possible metabolites in
      urine of rats. Histochrome was introduced to Wistar rats (n = 10) subcutaneously
      in a dose of 10 mg/kg. Naphthoquinone derivatives were extracted from the
      acidified urine by ethyl acetate and analyzed by high performance liquid
      chromatography with UV detection (HPLC/UV) and mass-spectrometric detection
      (HPLC/MS). It was established that histochrome is completely metabolized in an
      organism and excreted by kidneys in the form of 3-methoxy-2,5,6,8-tetrahydroxy-7
      ethyl-1,4-naphthoquinone and 2-metoxy-3,5,6,8-tetrahydroxy-7-ethyl-1,4
      naphthoquinone.

PMID- 25076758
TI  - [Preclinical study of AV0012 early stage inhibitor of hepatitis C virus
      infection: I. In vitro ADME and pharmacokinetics].
AB  - In vitro immunohistochemical investigations on the human hepatoma cell line
      (Huh7) infected with hepatitis C virus (HCV) strain JFH-1 showed that AV0012
      compound blocks the early stages of viral infection. AV0012 also blocked viral
      infection spread in tissue culture through the secreted virus and through tight
      cell-to-cell contact. AV0012 is a specific inhibitor of HCV but not of related
      pestivirus, flaviviruses and other RNA-containing viruses such as bovine diarrhea
      (BVDV), Venezuelan equine encephalitis (strain TC-83), dengue type 2 (New
      Guinea), yellow fever (strain 17D), west Nile fever, parainfluenza (type 3)
      virus, RSV (strain A2), and Rhinovirus (type 2 strain HGP). It is established
      that human serum does not significantly affect the antiviral activity of AV0012
      in vitro. The drug combination studies with AV0012 and interferon alpha 2a in
      vitro showed that the two inhibitors act additively, which makes possible the use
      of this combination in clinical tests. AV0012 is highly soluble and stable in
      aqueous solutions and murine blood plasma, has limited metabolic stability, low
      binding to human plasma proteins, high permeability through biological membranes,
      and only interacts with isoenzymes 2D6 and 3A4 of human cytochrome P450. In
      animal pharmacokinetic studies, AV0012 was rapidly absorbed into the blood stream
      upon oral administration, showed sufficiently long half-elimination times, and
      had high oral bioavailability that reached 92% in monkeys. Further preclinical
      development of AV0012 is in progress.

PMID- 25076759
TI  - [Clinical effectiveness of cytoflavin inclusion in intensive care of patients
      with combined traumatic brain injury].
AB  - Autors determine the clinical effectiveness of including cytoflavin in intensive
      care of patients with severe combined traumatic brain injury. A prospective blind
      randomized controlled study was conducted on two groups involving 101
      participants. In group I (58 patients), the intensive care was standard. In group
      II (43 patients), the intensive care included cytoflavin which was added
      beginning with the second day of the post-traumatic period. For this purpose, 10
      ml of cytoflavin was dissolved in 200 ml of 10% aqueous solution of glucose and
      was administered intravenously at a speed of 140 drops (7 ml) per minute within 7
      days. The use of cytoflavin in complex intensive care of severe combined
      traumatic brain injury within two days after injury (with the proper correction
      of blood circulation and respiration) reduced the number of multiple organ
      dysfunctions, the number is purulent-septic complications, the time of regress in
      multiple organ dysfunctions, and the reanimation period in intensive care
      department on the average by a factor of 1.4 - 1.6 (p < 0.005).

PMID- 25076760
TI  - [Rapid detection of mutations related to Mycobacterium leprae drug resistance by
      using Hp-rPCR (hairpin primer- real time PCR) method].
AB  - Rapid and simple detection method of drug resistance bacteria is required. In the
      present study, Hp-rPCR (hairpin primer-real time PCR) was applied to
      Mycobacterium leprae genes to detect mutations. Target sites of the method were
      as follows: first base and second base on 53rd codon and second base on 55th
      codon infolP1 gene for dapsone resistance, first base on 441st codon and 451st
      codon and second base on 456th and 458th codon in rpoB gene for rifampicin
      resistance, and first base on 89th codon and second base on 91st codon in gyrA
      gene for quinolone resistance which were common mutation sites in clinical
      reports. The total number of the target sites was 9. Mycobacterium leprae, Thai
      53, Zensho-2 and Zensho-4 were used as reference bacteria in the present study
      and clear, reliable results were obtained. Double-blind study was conducted using
      15 samples. The number of target sites was calculated as 135 in total by 9 sites
      in 15 samples. There was only one misreading in the blind samples and the
      sensitivity was more than 99%.

PMID- 25076761
TI  - [Review of WHO Expert Committee on Leprosy 8th report, --comparison to 7th
      report].
AB  - In 2012 the WHO Expert Committee on Leprosy published its 8th report, 14 years
      after the publication of its 7th report in 1998. This report, the first since the
      leprosy reduction goal was met in 2000, highlights key points such as
      improvements in the quality of various services available to patients and the
      efforts of individuals and societies, in addition to medical progress in
      diagnosis and treatment. This review will mainly describe the changes made since
      the 7th report. Some of the main modifications are the deletion of single lesion
      paucibacillary type, elongated treatment of patients with high bacterial indices,
      the introduction of promising new drugs, and a shift from reducing the
      statistical number of patients to a new target for disability prevention.

PMID- 25076762
TI  - Integrating food poverty and minimum cost diet methods into a single framework: a
      case study using a Nepalese household expenditure survey.
AB  - BACKGROUND: Current tools assessing affordability of nutritious diets are
      incomplete. "Food poverty" uses expenditure data to identify households unable to
      acquire a diet adequate in energy but does not consider other nutrients. The
      "minimum cost of a nutritious diet" method provides a threshold for purchasing a
      nutritious diet but must rely on other data to identify "nutrient-poor"
      households. OBJECTIVE: Integrating both methods into a single framework using a
      common data source, we sought to jointly estimate the proportions of a population
      that are food and nutrient poor. METHODS: Household expenditure data from the
      2010/11 Nepal Living Standards Survey were used, focusing on representative
      samples of households from the mountain region (n = 401) and Kathmandu (n = 857).
      Food poverty thresholds were set at the cost for a low-income household to
      purchase a basket of foods providing adequate energy following the Cost of Basic
      Need method. Linear optimization was used to calculate a "nutrient poverty"
      threshold. Household expenditures were used to determine food and nutrient
      poverty rates. RESULTS: The food and nutrient poverty thresholds were 13,294 and
      18,628 rupees/person/year, respectively, in the mountain region and 14,610 and
      22,945 rupees/ person/year, respectively, in Kathmandu. In the mountain region,
      34% of households were both food and nutrient poor and 24% were just nutrient
      poor. In Kathmandu the percentages were 7% and 14%, respectively. CONCLUSIONS:
      This approach, integrating two commonly used tools, provides a more nuanced
      interpretation of economic access to a nutritious diet and an opportunity to
      improve the design and targeting of nutrition and food security interventions.

PMID- 25076764
TI  - Determinants of stunting and overweight among young children and adolescents in
      sub-Saharan Africa.
AB  - BACKGROUND: Stunting and overweight are nutritional problems affecting most of
      sub-Saharan Africa. The region now has the world's highest rate of stunting among
      children (43%), while overweight and obesity are becoming a global epidemic, and
      Africa is not spared. The past two decades have seen a dramatic increase in
      obesity in sub-Saharan Africa. OBJECTIVE: The purpose of this systematic review
      is to explore the determinants of stunting and overweight in sub-Saharan Africa.
      METHODS: A literature search was conducted in PubMed using the key words
      stunting, overweight, obesity, Africa, sub-Saharan Africa, determinants, and
      prevalence. Limits were set to include articles published between 1990 and 2012.
      The systematic review resulted in 38 studies, and after selection based on title,
      content, and country of the study, 18 studies were eligible for this review. Data
      were analyzed by the chi-square test. RESULTS: The prevalence rates of stunting
      and overweight were dependent on socioeconomic, demographic, and environmental
      factors. Many studies indicate that male children and those living in a rural
      setting are more likely to be stunted, whereas overweight among children depends
      more on age, household composition, occupation of the mother, and the mother's
      body mass index. Stunting occurred together with overweight among both boys and
      girls from 1 to 5 years of age. Stunting was more prevalent among boys than among
      girls. Indicators of socioeconomic status, such as mother's education, mother's
      occupation, and household income, were some of the determinants directly linked
      to stunting, whereas environmental factors, such as rural or urban setting and
      sanitation, influenced both stunting and overweight. Concurrent stunting and
      overweight is influenced by maternal and household factors, such as maternal
      height, age, and education, large household size, and lower socioeconomic status.
      CONCLUSIONS: Although socioeconomic, demographic, and environmental factors were
      significant in determining stunting and overweight, other factors, such as
      nutrition and lifestyle, were important risk factors. Stunting in childhood is a
      risk factor that may result in overweight and obesity later in adolescence and
      adulthood, indicating the need to screen children below 1 year of age to identify
      stunting early in life. Promoting exclusive breastfeeding is reported to be
      important in preventing both stunting and overweight among children. More
      research is needed to explore the relationship between stunting and overweight
      and to explore policy guidelines to address the phenomenon.

PMID- 25076763
TI  - Hepcidin profile of anemic adolescent schoolgirls in Indonesia at the end of 12
      weeks of iron supplementation.
AB  - BACKGROUND: Iron deficiency is still the major nutritional problem in the
      developing world, and iron supplementation remains one of the most effective
      intervention strategies. Hepcidin, a newly discovered iron regulatory hormone, is
      an acute phase protein, and its role in iron supplementation has not been well
      explored. OBJECTIVE: To investigate the hepcidin profiles of anemic adolescent
      girls who had received weekly iron supplementation. METHODS: A cross-sectional
      study was conducted at the end of iron supplementation among adolescent
      schoolgirls (n = 83) in Pramuka Island, Indonesia. All the girls were anemic at
      the beginning and received 60 mg of elemental iron twice weekly for 12 weeks.
      Hemoglobin, hepcidin, serum ferritin, and red cell parameters were measured,
      together with inflammation markers. RESULTS: At the end of the 12-week
      supplementation, 65.1% (n = 64) of the girls were no longer anemic, but 43.4% (n
      = 36) were still iron deficient. The rate of subclinical inflammation, measured
      by C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP), was 38.6% (n =
      32). Hepcidin was not correlated with either ferritin or red cell parameters.
      There was no association between hepcidin and the inflammatory markers CRP and
      AGP. The mean hepcidin concentration was 42.9 +/- 17.9 ng/mL and was not
      significantly different between anemic and nonanemic girls (44.2 +/- 14.9 and
      42.3 +/- 19.2 ng/mL, respectively; p = .708). However, hepcidin concentration was
      slightly higher in the iron replete-group than in the iron-deficient group (45.2
      +/- 20.0 and 39.3 +/- 13.5 ng/mL, respectively), a suggestive trend that did not
      reach statistical significance (p = .218). CONCLUSIONS: Hepcidin concentrations
      tended to be higher among the subset of girls who responded poorly to iron
      supplementation as a consequence of increased subclinical inflammation. A
      longitudinal study should be conducted to explore the role of hepcidin in iron
      supplementation.

PMID- 25076765
TI  - Breastfeeding knowledge, attitude, perceived behavior, and intention among female
      undergraduate university students in the Middle East: the case of Lebanon and
      Syria.
AB  - BACKGROUND: The Middle East has one of the lowest rates of exclusive
      breastfeeding in the world, highlighting the need to promote breastfeeding in
      this region. Young adults represent a key population of interest, since decisions
      about infant-feeding appear to be made before children are even conceived.
      OBJECTIVE: To examine breastfeeding knowledge, attitude, and perceived behavior
      among female undergraduate students in Lebanon and Syria and determine factors
      associated with intention to breastfeed in this population. METHODS: This cross
      sectional study was conducted in 2010/11 in Damascus and Beirut. Four
      universities were selected in each city. A multicomponent questionnaire was
      administered to a convenience sample of participants (n = 194 from Beirut and n =
      199 from Damascus). The questionnaire included breastfeeding knowledge (measured
      by the Infant Feeding Knowledge Test Form), attitude (Iowa Infant Feeding
      Attitude Scale), perceived behavior (Breastfeeding Behavior Questionnaire), and
      intention (Infant Feeding Intention Scale). Factors associated with intention to
      breastfeed were examined by multivariate linear regression analysis. RESULTS: The
      participants had an average breastfeeding knowledge level (mean score, 10.39 +/-
      2.09) and neutral perceived behavior (mean score, 22.00 +/- 3.68), while having
      relatively positive attitudes (mean score, 58.12 +/- 6.49). Knowledge gaps and
      negative perceptions were identified, particularly linked to breastfeeding in
      public and among working mothers. Breastfeeding intention was found to be
      significantly associated with knowledge and attitude in Lebanon (beta = 0.103 and
      beta = 0.230, respectively), and with perceived behavior in Syria (beta = 
      0.135). CONCLUSIONS: By revealing specific knowledge gaps and misconceptions and
      identifying country-specific disparities in the predictors of the intention to
      breastfeed, the findings of this study may provide a basis for devising culture
      specific interventions aimed at promoting breastfeeding.

PMID- 25076766
TI  - Toward the prevention of childhood undernutrition: diet diversity strategies
      using locally produced food can overcome gaps in nutrient supply.
AB  - BACKGROUND: Chronic undernutrition is prevalent in Mozambique, where children
      suffer from stunting, vitamin A deficiency, anemia, and other nutrition-related
      disorders. Complete diet formulation products (CDFPs) are increasingly promoted
      to prevent chronic undernutrition. OBJECTIVE: Using linear programming, to
      investigate whether diet diversification using local foods should be prioritized
      in order to reduce the prevalence of chronic undernutrition. METHODS: Market
      prices of local foods were collected in Tete City, Mozambique. Linear programming
      was applied to calculate the cheapest possible fully nutritious food baskets
      (FNFB) by stepwise addition of micronutrient-dense localfoods. RESULTS: Only the
      top quintile of Mozambican households, using average expenditure data, could
      afford the FNFB that was designed using linear programming from a spectrum of
      local standard foods. The addition of beef heart or liver, dried fish and fresh
      moringa leaves, before applying linear programming decreased the price by a
      factor of up to 2.6. As a result, the top three quintiles could afford the FNFB
      optimized using both diversification strategy and linear programming. CDFPs, when
      added to the baskets, were unable to overcome the micronutrient gaps without
      greatly exceeding recommended energy intakes, due to their high ratio of energy
      to micronutrient density. CONCLUSIONS: Dietary diversification strategies using
      local, low-cost, nutrient-dense foods can meet all micronutrient recommendations
      and overcome all micronutrient gaps. The success of linear programming to
      identify a low-cost FNFB depends entirely on the investigators' ability to select
      appropriate micronutrient-dense foods. CDFPs added to food baskets are unable to
      overcome micronutrient gaps without greatly exceeding recommended energy intake.

PMID- 25076767
TI  - Will universal periodic vitamin A supplementation ever reach retirement age?

PMID- 25076768
TI  - A review of the vitamin A supplementation program in India: reasons for success
      in the states of Bihar and Odisha.
AB  - BACKGROUND: Preventive vitamin A supplementation (VAS) is an essential child
      survival intervention. In India, VAS program coverage has remained relatively
      low, with wide interstate variation. OBJECTIVE: To review the VAS program in
      India, particularly in Bihar and Odisha, the two states that have had the most
      successful VAS programs, to define best practices and identify critical success
      factors. METHODS: A thorough review of existing relevant literature was carried
      out, supplemented by field visits and interviews with selected partners. RESULTS:
      Both states have adopted a biannual approach to reach out to children 1 to 5
      years of age with VAS every 6 months, while infants below 1 year of age receive
      their first VAS dose with the measles immunization at 9 months. The critical
      success factors for the VAS program in the two states include strong leadership
      and ownership by the state government; close coordination between the two
      departments that are involved in the VAS program; effective microplanning prior
      to each biannual round; flexible dosing mechanisms that enhance coverage in hard
      to-reach areas; a stable procurement and distribution mechanism to ensure an
      adequate, timely, and sustainable supply of VAS; intensive social mobilization
      and communication; and appropriate training and supervision of staff.
      CONCLUSIONS: The governments of Bihar and Odisha have demonstrated that it is
      feasible to implement a successful and inclusive VAS program in India. The
      challenge now is to reach out to the remaining 30% to 40% of children who are
      undoubtedly the hardest to reach and potentially the most vulnerable.

PMID- 25076769
TI  - Evaluation of a residential nutrition rehabilitation center in rural Bolivia:
      short-term effectiveness and follow-up results.
AB  - BACKGROUND: Nutrition rehabilitation centers (NRCs) have shown mixed results in
      reducing morbidity and mortality among undernourished children in the developing
      world. Follow-up on children after leaving these programs remains undocumented.
      OBJECTIVE: To assess the nutritional improvement of children attending the Centro
      de Rehabilitacion Infantil Nutricional (CRIN), a residential NRC in rural
      Bolivia, from entrance to exit and to a household follow-up visit 1 month to 6
      years later, and to identify factors associated with nutritional improvement.
      METHODS: A retrospective analysis was conducted of clinical records collected by
      CRIN staff from 135 children under 3 years of age attending CRIN in rural
      Cochabamba, Bolivia, from 2003 to 2009, and of clinical records of household
      follow-up measurements on a subset of 26 children that were taken between 1 month
      and 6 years postexit. Nutritional status was evaluated by calculating z-scores
      for weight-for-height (WHZ), weight-for-age (WAZ), and height-for-age (HAZ).
      Children with z-scores < -2 were considered to be wasted, underweight, or
      stunted, respectively. RESULTS: The prevalence of wasting decreased
      significantly, while the prevalence of stunting did not change significantly
      between entrance and exit from the program. From entrance to exit, the mean
      changes in WHZ (0.79) and WAZ (1.08) were statistically significant, while the
      mean change in HAZ (-0.02) was not significant. Linear regression analysis
      suggested that nutritional status and diarrhea at entrance had the greatest
      effect on WHZ and HAZ changes between entrance and exit. Children maintained
      their nutritional gains from the program between exit and follow-up and showed
      statistically significant improvement in WAZ (but not HAZ). CONCLUSIONS: CRIN is
      effective at rehabilitating nutritional deficits associated with wasting, but not
      those associated with stunting.

PMID- 25076770
TI  - Design and development of a combined calcium-iron-folic acid prenatal supplement
      to support implementation of the new World Health Organization recommendations
      for calcium supplementation during pregnancy.
AB  - BACKGROUND: Hypertensive diseases of pregnancy are important causes of maternal
      and perinatal mortality. Based on meta-analyses of efficacy trials of prenatal
      calcium supplementation to reduce the risk of hypertensive diseases of pregnancy,
      the World Health Organization recommends 1.5 to 2.0 g of elemental calcium per
      day for pregnant women with low dietary calcium intakes (as well as 60 mg of iron
      and 400 microg of folic acid). However, implementation of this recommendation is
      challenged by the size and number of calcium tablets required and the need to
      avoid concurrent ingestion of calcium and iron due to intraintestinal
      interactions. OBJECTIVE: We developed a novel micronutrient powder containing
      microencapsulated pH-sensitive calcium in addition to iron and folic acid,
      designed to facilitate early intestinal iron release and delayed calcium release.
      METHODS: Two pharmaceutical companies were contracted to develop a prototype, one
      of which was chosen for clinical testing. Calcium carbonate granules were coated
      with a trilayer pH-sensitive enteric coating using a fluid-bed spray coater. Iron
      and folic acid granules were encapsulated with a time-release coating. Iron and
      calcium dissolution profiles were assessed during exposure to acidic (pH 1.2)
      and/or basic (pH 5.8) media using a modified USP apparatus 1 (basket) method.
      RESULTS: At pH 1.2, calcium and iron release was < or = 10% and > 90% after 120
      minutes, respectively. At pH 5.8, > 80% of total calcium was released after 90
      minutes. CONCLUSIONS: Based on in vitro criteria, the supplement may be a
      promising approach for delivering calcium, iron, and folic acid as a single daily
      dose to pregnant women in settings of low dietary intake of calcium.

PMID- 25076772
TI  - Changing dietary patterns in the Canadian Arctic: frequency of consumption of
      foods and beverages by inuit in three Nunavut communities.
AB  - BACKGROUND: Inuit in Arctic regions are experiencing a rapid diet and lifestyle
      transition. There are limited data on food consumption patterns among this unique
      population, raising concerns about assessing the risk for the development of diet
      related chronic diseases. OBJECTIVE: To assess the current frequency of
      consumption of foods and beverages among Inuit in Nunavut, Arctic Canada.
      METHODS: A cross-sectional dietary study was conducted among randomly selected
      Inuit adults from three communities in Nunavut using a validated quantitative
      food frequency questionnaire. The participants were 175 women and 36 men with
      median (IQR) ages of 41.0 (32.5-48.5) and 40.1 (30.0-50.0) years, respectively.
      The mean and median frequencies of consumption over a 30-day period were computed
      for 147 individual food items and grouped as foods or beverages. RESULTS: The 30
      most frequently consumed foods were identified. Non-nutrient-dense foods (i.e.,
      high-fat and high-sugar foods) were the most frequently consumed food group
      (median intake, 3.4 times/day), followed by grains (2.0 times/day) and
      traditional meats (1.7 times/day). The frequency of consumption of fruits (0.7
      times/day) and vegetables (0.4 times/day) was low. The median values for the
      three most frequently consumed food items were sugar or honey (once/day), butter
      (0.71 times/day), and Coffee-mate (0.71 times/day). Apart from water, coffee, and
      tea, the most frequently consumed beverages were sweetened juices (0.71
      times/day) and regular pop (soft drinks) (0.36 times/day). This study showed that
      non-nutrient-dense foods are consumed most frequently in these Inuit communities.
      CONCLUSIONS: The results have implications for dietary quality and provide useful
      information on current dietary practices to guide nutritional intervention
      programs.

PMID- 25076773
TI  - The Indian National Food Security Act, 2013: a commentary.
AB  - The National Food Security Act (NFSA) 2013, passed recently by the Indian
      Parliament, aims to ensure food security in India, chiefly by providing cereals
      at subsidized prices through the Targeted Public Distribution System (TPDS) for
      about two-thirds of households. The predominant line of criticism of the NFSA has
      been the costs of such an ambitious rights-based approach in the context of
      decelerating economic growth and growing fiscal deficits. We argue that the food
      subsidy has been increasing through the last few decades and is set to climb even
      higher with this act but that the incremental costs, at about 0.2% of gross
      domestic product, are not as high as claimed. Further, recent evidence of
      increasing utilization of the TPDS and decreasing corruption add credence to the
      act's premise that significant income transfers to poor households can be
      achieved, thereby promoting food security as well as dietary diversity. Several
      concerns remain to be addressed in the design and implementation of the act,
      including its proposed coverage, a cereal-centric approach, the identification of
      beneficiaries, and its adaptability at the state level. If these are resolved
      effectively, the act can prove to be a significant step forward in India's long
      drawn-out battle against undernutrition and food insecurity. Finally, the NFSA
      also provides a fresh opportunity to reform and strengthen the TPDS, which has
      been an integral component of India's strategy to achieve food security at the
      national level.

PMID- 25076774
TI  - Which aid spending categories have the greatest untapped potential to support the
      reduction of undernutrition? Some ideas on moving forward.
AB  - The financial resource needs for the reduction of undernutrition are significant,
      while the returns from reducing undernutrition are large. Yet the share of public
      resources allocated to the reduction of undernutrition remains disproportionately
      small. For overseas development assistance, the investment in nutrition-specific
      and nutrition-sensitive categories amounts to less than 3% of the total. What is
      the potential for other categories of public resource investments to reduce
      undernutrition, and in which sectors are these investments to be found? This
      paper proposes a framework for addressing this question and ventures some
      suggestions as to which of the categories of overseas development assistance
      beyond the well-known "nutrition-specific" and "nutrition-sensitive" categories
      are most likely to yield improvements in nutrition status if they could be
      redesigned with this in mind. We conclude that policy makers should look widely
      within the underlying and basic determinant intervention space for investments
      that, when changed at the margins, could result in significant improvements in
      nutrition.

PMID- 25076771
TI  - Childhood dual burden of under- and overnutrition in low- and middle-income
      countries: a critical review.
AB  - BACKGROUND: In low- and middle-income countries, the distribution of childhood
      nutritional diseases is shifting from a predominance of undernutrition to a dual
      burden of under- and overnutrition. This novel and complex problem challenges
      governments and health organizations to tackle opposite ends of the malnutrition
      spectrum. The dual burden may manifest within a community, household, or
      individual, but these different levels have not been addressed collectively.
      OBJECTIVE: To critically review literature on the prevalence, trends, and
      predictors of the dual burden, with a focus on children from birth to 18 years of
      age. METHODS: We reviewed literature since January 1, 1990, published in English,
      using the PubMed search terms nutrition transition, double burden, dual burden,
      nutrition status, obesity, overweight, underweight, stunting, body composition,
      and micronutrient deficiencies. The findings were classified and described
      according to dual burden level (community, household, or individual). RESULTS:
      Global trends indicate decreases in diseases of undernutrition, while
      overnutrition is increasing. On the community level, economic status may
      influence the extent of the dual burden, with obesity increasingly affecting the
      already undernourished poor. In a household, shared determinants of poor
      nutritional status among members can result in disparate nutritional status
      across generations. Within an individual, obesity may co-occur with stunting or
      anemia due to shared underlying determinants or physiologic links. CONCLUSIONS:
      The dual burden of malnutrition poses a threat to children's health in low- and
      middle-income countries. We must remain committed to reducing undernutrition
      while simultaneously preventing over-nutrition through integrated child health
      programs that incorporate prevention of infection, diet quality, and physical
      activity.

PMID- 25076775
TI  - Community-based management of acute malnutrition in Bangladesh: feasibility and
      constraints.
AB  - BACKGROUND: To achieve the United Nations Millennium Development Goals,
      particularly reduction in child mortality (Millennium Development Goal 4),
      effective interventions to address severe and moderate acute malnutrition (SAM
      and MAM) among children under 5 years of age must be implemented and brought to
      scale alongside preventive measures. Bangladesh has an estimated 600,000 children
      with SAM, for a prevalence of 4%, while 1.8 million children suffer from MAM.
      OBJECTIVE: To assess the feasibility and constraints of community-based
      management of acute malnutrition (CMAM), a relatively new approach, in managing
      SAM and MAM among children in Bangladesh. METHODS: The methodology involved desk
      reviews of documents by searching through PubMed and other databases for
      published literature on CMAM in Bangladesh. We also did a hand search of policy
      and program documents, including the draft National Nutrition Policy 2013; the
      Health, Nutrition, Population Sector Development Program document of the Ministry
      of Health and Family Welfare, Government of Bangladesh; the Sixth Five Year Plan;
      and the Operational Plans of the National Nutrition Services of Bangladesh.
      RESULTS: . The conventional approach in Bangladesh has been to treat children
      suffering from SAM and associated complications in hospital settings. There is no
      program to take care of children with MAM. There is a dearth of local evidence to
      operationalize and implement CMAM in the context of Bangladesh. This paper
      summarizes the scientific literature and rationale for the implementation of CMAM
      in Bangladesh. It also provides recommendations to improve health strategies
      related to CMAM, discusses diets being developed that may result in better
      implementation of CMAM, and offers recommendations for areas of additional
      necessary research. CONCLUSIONS: A recommended approach for Bangladesh on the
      management of acute malnutrition would be to integrate CMAM into the rollout of
      the National Nutrition Services so that screening, identification, referral, and
      treatment of acutely malnourished children could be effectively managed within
      the community-based health service delivery system. Given that the vast majority
      of children are suffering from MAM and could be treated with locally developed
      food supplements, a significant emphasis of the CMAM approach in Bangladesh
      should be to screen and treat MAM. Over time, this would also result in fewer SAM
      cases. However, even with this approach, there would still be a small number of
      children who have SAM and who ideally should be treated with specialized
      therapeutic foods. While the Government of Bangladesh is awaiting full-scale
      production of a local ready-to-use therapeutic food (RUTF), an interim strategy
      is needed to effectively treat these severely wasted children on an outpatient
      basis.

PMID- 25076776
TI  - [Immaturity of brain as an endophenotype of neuropsychiatric disorders].
AB  - Schizophrenia and bipolar disorder are severe neuropsychiatric disorders,
      affecting about 1% of the population. Identifying endophenotypes in the brains of
      neuropsychiatric patients is now considered the way to understand the underlying
      mechanisms and to improve therapeutic outcomes. However, the endophenotypes and
      brain mechanisms of the disorders remain unknown. We have previously reported
      that alpha-CaMKII heterozygous knockout mice show abnormal behaviors related to
      neuropsychiatric disorders. In these mutant mice, almost all neurons in the
      hippocampal dentate gyrus stay at a pseudo-immature state, which we refer to as
      "immature dentate gyrus (iDG)." So far, the iDG phenotype and similar behavioral
      abnormalities have been found in Schnurri-2 knockout, SNAP-25 mutant, and
      forebrain-specific calcineurin knockout mice. In addition, we found that both
      chronic fluoxetine treatment and pilocarpine-induced seizures can reverse the
      maturation state of the mature neurons, resulting in the iDG phenotype in wild
      type mice. Such an iDG-like phenomenon was observed in the post-mortem brains
      from patients with schizophrenia/bipolar disorder. Recent studies suggest that
      cortex and amygdala of schizophrenia patients are also at a pseudo-immature
      state. Based on the findings, we proposed that immaturity of certain types of
      cells in the brain is a potential endophenotype of neuropsychiatric disorders.

PMID- 25076777
TI  - [An introduction of the Translational Medical Science Committee (TMSC) of the
      Japanese Society of Neuropsychopharmacology].
AB  - The Japanese Society of Neuropsychopharmacology (NP) has established a
      Translational Medical Science Committee (TMSC), which is introduced in this
      article. In this century, the Japanese Government has made great effort to
      establish highly organized supporting systems for translational research (TR);
      however, clinical developments for psychotropic drugs in Japan are facing
      stagnation. TMSC will provide advisory activities from an academic point of view
      in this field, which will be result in the improvement of people's health.

PMID- 25076778
TI  - [Regulation of neural circuit function in the axon initial segment].
AB  - The axon initial segment (AIS) is a highly specialized neuronal subregion that
      separates axonal and somatodendritic compartments. The AIS is enriched with
      voltage-gated Na+ channels, and plays a critical role in determining neuronal
      activity. Recently, our understanding of AIS has seen major advances. Types and
      density of ion channels within the AIS vary among different neuronal types, which
      may underlie the variations in firing of neurons in the brain. Distribution of
      the AIS itself is not uniform among neurons either; rather, it is delicately
      determined in each neuron to meet its specific need. Furthermore, the AIS has a
      capacity for plasticity and reorganizes its distribution to regulate neural
      activity. In this review, I will show how these newly found features of AIS
      contribute to shape the function of neural circuits that are involved in the
      integration of binaural timing information for sound localization in birds.

PMID- 25076779
TI  - [The involvement of hippocampal cholinergic neurostimulating peptide and its
      precursor in Alzheimer pathogenesis].
AB  - Hippocampal cholinergic neruostimulating peptide (HCNP) induces acethylcholine
      synthesis in the adult hippocampus of mice via increasing the amount of
      cholineacethyl transferase. The precursor protein of HCNP (HCNP-pp), composed of
      186 amino acids, is a multifunctional protein, such as c-Raf kinase inhibitory
      protein and phosphatidylethanolamine-binding protein. In the adult hippocampus,
      HCNP-pp co-localizes in presynapse terminals with non-phosphorylated collapsin
      response mediator protein (CRMP)-2, and might play a crucial role in hippocampal
      neuronal activity. The quantitative alteration of HCNP-pp might be related to the
      phosphorylation of CRMP-2. The expression of HCNP-pp mRNA is decreased in
      hippocampal pyramidal neurons of CA1 from the early stage in Alzheimer's disease.
      The HCNP-related antigens are also deposited in the Hirano body, one locus of
      Alzheimer pathology. CRMP-2 is one of microtubule-associated proteins such as tau
      protein, and its phosphorylated form increased in the hippocampus of Alzheimer
      brains. HCNP and HCNP-pp might be candidates for the key molecules as a
      therapeutic target in Alzheimer's disease.

PMID- 25076780
TI  - [Individualized immunosuppressive therapy after liver transplantation focusing on
      detoxifying mechanisms].

PMID- 25076781
TI  - A rare case of a bronchial anomaly running in the hilar region from the right
      lower lobe to the middle lobe.
AB  - A 77-year-old male was referred to our department due to lung cancer (cT3N0M0) of
      the right lower lobe. During right lower lobectomy, a thin duct structure was
      recognized in the hilar region between the middle and lower lobes that was
      identified to be a supernumerary bronchus upon a review of the preoperative chest
      CT images. Although bronchial anomalies are rare, it is important to carefully
      view preoperative images for any such anomalies in order to more safely perform
      surgery.

PMID- 25076782
TI  - Gastric glomus tumor diagnosed by endoscopic ultrasound-guided fine-needle
      aspiration biopsy: report of a case.
AB  - A glomus tumor of the stomach is rare. It is difficult to diagnose the tumor
      before surgery by only endoscopic biopsy and radiography, and there is no
      established method of diagnosis before surgical treatment.
      Esophagogastroduodenoscopy (EGD) on a 50-year-old Japanese woman revealed a 10 mm
      submucosal tumor in the anterior wall of the gastric angle. Follow-up EGD
      revealed an increase in the size of the tumor to 15mm. Endoscopic ultrasonography
      (EUS) demonstrated a 15mm subepithelial hypoechoic solid tumor with continuity to
      the proper muscle layer. Histologic diagnosis by endoscopic ultrasonography
      guided fine needle aspiration (EUS-FNA) was glomus tumor. The tumor was treated
      by laparoscopic local resection. The histologic diagnosis of the resected tumor
      was similar to the preoperative EUS-FNA results. EUS-FNA would appear to be an
      effective histologic test for early diagnosis of gastric glomus tumor.

PMID- 25076783
TI  - Changes in Transportation Infrastructure and Commuting Patterns in U.S.
      Metropolitan Areas, 1960-2000.

PMID- 25076784
TI  - How Relevant Is Malthus for Economic Development Today?

PMID- 25076785
TI  - INSTITUTIONS AND BEHAVIOR: EXPERIMENTAL EVIDENCE ON THE EFFECTS OF DEMOCRACY.
AB  - A novel experiment is used to show that the effect of a policy on the level of
      cooperation is greater when it is chosen democratically by the subjects than when
      it is exogenously imposed. In contrast to the previous literature, our
      experimental design allows us to control for selection effects (e.g. those who
      choose the policy may be affected differently by it). Our finding implies that
      democratic institutions may affect behavior directly in addition to having
      effects through the choice of policies. Our findings have implications for the
      generalizability of the results of randomized policy interventions.

PMID- 25076786
TI  - A Bright Idea for Measuring Economic Growth.

PMID- 25076787
TI  - School Desegregation, School Choice and Changes in Residential Location Patterns
      by Race.
AB  - This paper examines the residential location and school choice responses to the
      desegregation of large urban public school districts. We decompose the well
      documented decline in white public enrollment following desegregation into
      migration to suburban districts and increased private school enrollment, and find
      that migration was the more prevalent response. Desegregation caused black public
      enrollment to increase significantly outside of the South, mostly by slowing
      decentralization of black households to the suburbs, and large black private
      school enrollment declines in southern districts. Central district school
      desegregation generated only a small portion of overall urban population
      decentralization between 1960 and 1990.

PMID- 25076788
TI  - The Antioxidant Activity and Oxidative Stability of Cold-Pressed Oils.
AB  - In our study, we characterized the antioxidant activity and oxidative stability
      of cold-pressed macadamia, avocado, sesame, safflower, pumpkin, rose hip, Linola,
      flaxseed, walnut, hempseed, poppy, and milk thistle oils. The radical scavenging
      activity of the non-fractionated fresh oil, as well as the lipophilic and
      hydrophilic fractions of the oil was determined using a 1,1-diphenyl-2
      picrylhydrazyl (DPPH) assay. The fatty acid composition of the fresh and stored
      oils was analyzed by gas chromatography. The acid value, peroxide value, p
      anisidine value and conjugated diene and triene contents in the fresh oils, as
      well as in those stored throughout the whole period of their shelf life, were
      measured by CEN ISO methods. The antioxidant activity of the oils expressed as
      Trolox equivalent antioxidant capacity (TEAC), ranged from 0.17 to 2.32 mM. The
      lipophilic fractions of the oils were characterized by much higher antioxidant
      activity than the hydrophilic ones. There were no significant changes in fatty
      acid composition and only slight changes in the oxidative stability parameters of
      the oils during their shelf life. Through the assessment of the relationship
      between antiradical activity and the oxidative stability of oils, it is proposed
      that a DPPH assay predicts the formation of oxidation products in cold-pressed
      oils-however, the correlations differ in fractionated and nonfractionated oils.

PMID- 25076789
TI  - Strong personalities, not social niches, drive individual differences in social
      behaviours in sticklebacks.
AB  - Understanding the mechanisms responsible for consistent individual differences in
      behaviour is a recent challenge for behavioural ecology. Although theory is
      rapidly developing in this area, there are few empirical tests. There are at
      least two hypotheses to explain why individuals behave differently from one
      another in a dynamic social environment. The social niche specialization
      hypothesis proposes that repeated social interactions generate consistent
      individual differences in social behaviour. The behavioural type hypothesis
      proposes that an individual's social behaviour reflects its behavioural type. We
      tested these two hypotheses by manipulating the opportunity for repeated social
      interactions in groups of three spine stickleback, Gasterosteus aculeatus, and by
      measuring the behavioural types of the same individuals in three contexts: when
      in a novel environment, when presented with an opportunity to associate with
      conspecifics and when confronted by an intruder. We found no evidence that
      repeated social interactions increased between-individual variation in social
      foraging behaviour. Instead, individuals' social foraging behaviour was related
      to their behavioural type, specifically their shoaling behaviour. In addition,
      the behavioural types of the members of a group strongly influenced a group's
      average foraging behaviour. Together, these results do not support the hypothesis
      that social dynamics within groups generates individual differences in behaviour.
      Instead, they suggest the reverse: individual differences in behaviour drive
      group-level dynamics.

PMID- 25076790
TI  - Subcutaneous Administration of Monoclonal Antibodies in Oncology.
AB  - Treatment with monoclonal antibodies (mabs) has become an established component
      of oncological therapy. The monoclonal antibodies available for this purpose are
      mainly administered intravenously in individually adapted doses according to body
      weight over longer treatment times. For other chronic diseases such as, for
      example, diabetes mellitus, the subcutaneous administration of drugs is an
      established therapy option. For the subcutaneous administration of larger volumes
      as needed for mab solutions the extracellular matrix of the subcutaneous tissue
      represents a problem. The co-formulation with recombinant human hyaluronidase
      makes the relatively pain-free administration of larger fluid volumes and thus
      the subcutaneous administration of monoclonal antibodies possible, as illustrated
      by the development of a subcutaneous formulation of trastuzumab. This constitutes
      a less invasive, time-optimised and flexible form of administration for patients
      with HER2-positive breast cancer that, with its fixed dosing possibilities,
      contributes to therapeutic safety. The example of trastuzumab shows that the
      subcutaneous administration of monoclonal antibodies can simplify oncological
      long-term therapy not only for the patients but also for the medical personnel.

PMID- 25076791
TI  - Influence of Mifepristone in Induction Time for Terminations in the Second and
      Third Trimester.
AB  - Termination of pregnancy after the first trimester is generally carried out by
      medical induction. Question: The aim of this study is to investigate the effect
      of mifepristone before administration of the prostaglandin derivative on
      induction time. Material and Methods: We analysed 333 medically indicated
      terminations after the first trimester under the terms of S 218 a Para. 2 of the
      German Criminal Code, in which the prostaglandin derivatives misoprostol,
      gemeprost or dinoprostone were administered with or without pre-treatment with
      600 mg of mifepristone. The time interval between the initial administration of
      prostaglandin and delivery was investigated. Using uni- and multivariate
      regression analysis, the effect of maternal age, body mass index, gravidity and
      parity, previous Caesarean sections, gestational age and the induction regimen on
      the induction time were analysed. Results: The average induction time was
      significantly shortened with mifepristone (15.1 +/- 11.9 hours with mifepristone
      vs. 25.3 +/- 24.2 hours without mifepristone [p < 0.001]). The combination of
      mifepristone and misoprostol was most frequently used and proved to be the most
      effective regimen, reducing the induction period to 13.6 +/- 10.3 hours. Besides
      pre-treatment with mifepristone, gestational age and a history of delivery
      without Caesarean section were significant influencing factors in reducing the
      induction time. Conclusion: The induction interval can be significantly shortened
      by the prior administration of mifepristone. The combination of mifepristone and
      misoprostol or gemeprost is the most effective regimen for the medical
      termination of pregnancy.

PMID- 25076792
TI  - Three-Day Combination Treatment for Vulvovaginal Candidosis with 200 mg
      Clotrimazol Vaginal Suppositories and Clotrimazol Cream for the Vulva is
      Significantly Better than Treatment with Vaginal Suppositories Alone - an
      Earlier, Multi-Centre, Placebo-Controlled Double Blind Study.
AB  - Problem: According to the guidelines, acute vulvovaginal candidosis (VVC) may be
      treated vaginally, through a combination of vaginal treatment and cream for the
      vulva or orally. However, there is a lack of investigations into whether combined
      treatment for the vagina and vulva achieves better results than vaginal treatment
      alone. Method: In 1999, 160 patients with vulvovaginal candidosis from ten German
      gynaecological practices were included in a study and treated on a randomised
      basis with three 200 mg clotrimazol vaginal suppositories = clotrimazol 2 % cream
      (verum n = 79) or + placebo (active-ingredient-free cream base n = 79). The
      examinations took place before treatment (T1), six to eight days following the
      end of treatment (T2) and approximately four weeks following the end of treatment
      (T3). In addition to demographic data, the clinical findings of each
      investigation were documented in a standardised way and a native preparation and
      a fungal culture were taken. The doctor and patient evaluated the healing process
      and tolerance. The main efficacy variables were the pre/post difference scores
      for extravaginal redness. Results: On T1, there was no difference between the two
      groups. By T2, there was a significant difference in the extent of extravaginal
      redness between the verum and the placebo groups (p = 0.0002), as well as in the
      subgroup of the per-protocol analysis (verum 64, placebo 70 patients, p =
      0.0015). Genital itching or burning had entirely disappeared in 51 % and 56 % of
      patients respectively in the verum group and in only 30 % and 45 % of patients in
      the placebo group on T2 (p = 0.0181). There was no difference in intravaginal
      redness on T1 and T2 in either group. The overall assessment by the doctor went
      accordingly (p = 0.0004). On T1, the extravaginal fungal culture was positive in
      75 women in the verum group and in 76 women in the placebo group. On T2, however,
      this was positive in 51.9 % (verum) and 73.1 % (placebo) of cases, and a positive
      culture was evinced in the vagina in 6 vs. 8 women (7.5 vs. 10.1 %, p = 0.3802).
      The local tolerance in both groups was 70 % very good, and 29 vs. 27 % good.
      After four weeks (T3), 16 out of 23 patients in the verum group and only 8 out of
      21 in the placebo group had negative extravaginal fungal cultures. Discussion:
      There is a lack of studies into the issue of whether vaginal treatment or
      combined vulvovaginal treatment of acute VVC would be more advantageous. However,
      there are two studies that support the significant results of this paper that
      when it comes to acute VVC, the combination of three 200 mg clotrimazol vaginal
      suppositories with clotrimazol cream 2 % is better than with vaginal
      suppositories alone.

PMID- 25076793
TI  - Patients and Methods of the PATH Biobank - A Resource for Breast Cancer Research.
AB  - Introduction: The foundation PATH (Patients' Tumour Bank of Hope) collects in a
      tumour bank samples of blood, tumour, and tumour-near normal tissue from breast
      cancer patients and supplements them systematically with health-care data.
      Material and Methods: For patients from the diagnosis years 2006-2009
      quantitative data were evaluated with the help of mean values and standard
      deviations while for qualitative data absolute and relative incidences were
      assessed. Demographic and clinical features of women who used different numbers
      of information sources were tested for statistical significance by means of ANOVA
      and chi2 tests. The benchmark report of the WBC and two DMP reports were used to
      compare oncological care. Results: For research purposes tumour tissue samples
      are available for 59 % of the cases, normal tissue for 62 % and blood serum
      samples for 92 %. From 3573 women (diagnoses 2006-2009), a total of 2697 women
      (75.5 %) took part in follow-up. The characteristics of the follow-up patients
      did not relevantly differ from those of all the patients. The responsible
      physician was named as the most important source of information about the
      disease. Young women in particular consulted several sources and also used the
      internet to obtain information. Discussion: Compared with data on therapy from
      WBC and the DMP breast cancer in Bavaria or, respectively, North Rhineland
      reports, the PATH patients represent an only slightly selected sample. The PATH
      biobank is a (still) poorly used data and sample source, which is made available
      upon request and positive evaluation of the study protocol. Thus, it is possible
      to address current questions in a short time without having to undertake
      extensive recruiting procedures.

PMID- 25076794
TI  - Use of an Additional Diagnostic Work-up Following a Treatment Recommendation from
      the Preoperative Conference of the Mammography Screening Units.
AB  - Objective: If a focus of suspicion is classified as being B 3-5 by a punch biopsy
      as part of a mammography screening, a recommendation for further action to be
      taken will be given in the preoperative conference of the screening unit. As part
      of this investigation, these treatment recommendations were compared with the
      final therapeutic approach taken at a certified breast centre. Furthermore, it
      was investigated whether and which additional examinations were performed on
      patients, depending on compliance with the recommended treatment. Material and
      Method: The data from 272 breast cancer patients from the years 2007, 2008 and
      2009 was analysed. The patients took part in the screening programmes of four
      screening units in the German mammography screening programme, in one federal
      state. In addition, the data from each patient from one screening unit was
      analysed in two further federal states. Results: In total, the most recently
      conducted intervention deviated from the treatment recommendation from the
      preoperative conference in the screening unit in 77 out of 272 patients (28.3 %).
      Of these, there were 50 recommendations for open biopsy which ultimately resulted
      in breast-conserving surgery, which is not to be evaluated as an error, as the
      bioptic result was supplemented by the open biopsy. Additional examinations were
      performed in patients with deviating treatment recommendation in 39 cases (50.6
      %) and in patients without deviating treatment recommendation in 66 cases (34.0
      %). The additional examinations carried out included additional punch biopsies
      (most frequent) and MRI scans, but also additional ultrasounds or a mammography.
      Conclusions: Additional examinations lead to a change in treatment in a higher
      percentage of patients in comparison with the initial screening including
      assessment. An exact reexamination of the findings obtained in the screening is
      therefore preoperatively necessary in order to guarantee optimum treatment.

PMID- 25076795
TI  - Rupture of the Left Renal Fornix after Vaginal Repair of Postpartum Vesicovaginal
      Fistula.
AB  - Surgical repair of vesicovaginal fistulas carries a risk of postoperative
      obstruction of the upper urinary tract. In the case described here, a
      postoperative intramural edema led to urinary retention and subsequent rupture of
      the renal pelvis. This is a rare but typical urological emergency. If patients
      complain postoperatively of flank pain, ultrasound should be carried out
      promptly. If the findings are unclear (no urinary retention despite clinical
      symptoms), additional computed tomography should be performed to determine
      whether rupture of the fornix has occurred.

PMID- 25076796
TI  - Spatial, Temporal and Spatio-Temporal Patterns of Maritime Piracy.
AB  - OBJECTIVES: To examine patterns in the timing and location of incidents of
      maritime piracy to see whether, like many urban crimes, attacks cluster in space
      and time. METHODS: Data for all incidents of maritime piracy worldwide recorded
      by the National Geospatial Intelligence Agency are analyzed using time-series
      models and methods originally developed to detect disease contagion. RESULTS: At
      the macro level, analyses suggest that incidents of pirate attacks are
      concentrated in five subregions of the earth's oceans and that the time series
      for these different subregions differ. At the micro level, analyses suggest that
      for the last 16 years (or more), pirate attacks appear to cluster in space and
      time suggesting that patterns are not static but are also not random.
      CONCLUSIONS: Much like other types of crime, pirate attacks cluster in space, and
      following an attack at one location the risk of others at the same location or
      nearby is temporarily elevated. The identification of such regularities has
      implications for the understanding of maritime piracy and for predicting the
      future locations of attacks.

PMID- 25076797
TI  - A Stab in the Dark?: A Research Note on Temporal Patterns of Street Robbery.
AB  - OBJECTIVES: Test the influence of darkness in the street robbery crime event
      alongside temperature. METHODS: Negative binomial regression models tested
      darkness and temperature as predictors of street robbery. Units of analysis were
      four 6-hr time intervals in two U.K. study areas that have different levels of
      darkness and variations of temperature throughout the year. RESULTS: Darkness is
      a key factor related to robbery events in both study areas. Traversing from full
      daylight to full darkness increased the predicted volume of robbery by a multiple
      of 2.6 in London and 1.2 in Glasgow. Temperature was significant only in the
      London study area. Interaction terms did not enhance the predictive power of the
      models. CONCLUSION: Darkness is an important driving factor in seasonal variation
      of street robbery. A further implication of the research is that time of the day
      patterns are crucial to understanding seasonal trends in crime data.

PMID- 25076798
TI  - Resistance in Unjust Times: Archer, Structured Agency and the Sociology of Health
      Inequalities.
AB  - Few sociologists dissent from the notion that the mid- to late 1970s witnessed a
      shift in capitalism's modus operandi. Its association with a rapid increase of
      social and material inequality is beyond dispute. This article opens with a brief
      summation of contemporary British trends in economic inequalities, and finds an
      echo of these trends in health inequalities. It is suggested that the sociology
      of health inequalities in Britain lacks an analysis of agency, and that such an
      analysis is crucial. A case is made that the recent critical realist contribution
      of Margaret Archer on 'internal conversations' lends itself to an understanding
      of agency that is salient here. The article develops her typology of internal
      conversations to present characterizations of the 'focused autonomous reflexives'
      whose mind-sets are causally efficacious for producing and reproducing
      inequalities, and the 'dedicated meta-reflexives' whose casts of mind might yet
      predispose them to mobilize resistance to inequalities.

PMID- 25076799
TI  - THE NONEQUIVALENT HEALTH OF HIGH SCHOOL EQUIVALENTS.
AB  - OBJECTIVES: Millions of U.S. adults are recipients of the high school equivalency
      (GED) diploma. Virtually nothing is known about the health of this large group,
      although literature suggests GED recipients are considerably worse off than high
      school graduates in numerous economic and social outcomes. We analyze general
      health among working-age adults with a high school diploma, GED recipients, and
      high school dropouts. METHODS: Ordered and binary logistic models of self-rated
      health and activity limitations were estimated using data from the 1997-2009
      National Health Interview Surveys (N=76,703). RESULTS: GED recipients have
      significantly and substantially worse health than high school graduates, among
      both sexes. In fact, the GED recipients' health is generally comparable to that
      of high school dropouts. Health behaviors and economic factors explain a large
      proportion of the difference but the gap remains significant. CONCLUSIONS: In
      terms of health, adults with a terminal GED are not equivalent to high school
      graduates. GED recipients report considerably worse general health and activity
      limitations. The disadvantage is only partly due to the worse economic outcomes
      and health behaviors; a significant difference remains unexplained and may be due
      to other, unobserved pathways, or to selection mechanisms.

PMID- 25076800
TI  - Compound p-value statistics for multiple testing procedures.
AB  - Many multiple testing procedures make use of the p-values from the individual
      pairs of hypothesis tests, and are valid if the p-value statistics are
      independent and uniformly distributed under the null hypotheses. However, it has
      recently been shown that these types of multiple testing procedures are
      inefficient since such p-values do not depend upon all of the available data.
      This paper provides tools for constructing compound p-value statistics, which are
      those that depend upon all of the available data, but still satisfy the
      conditions of independence and uniformity under the null hypotheses. Several
      examples are provided, including a class of compound p-value statistics for
      testing location shifts. It is demonstrated, both analytically and through
      simulations, that multiple testing procedures tend to reject more false null
      hypotheses when applied to these compound p-values rather than the usual p
      values, and at the same time still guarantee the desired type I error rate
      control. The compound p-values are used to analyze a real microarray data set and
      allow for more rejected null hypotheses.

PMID- 25076802
TI  - Functional Causal Mediation Analysis With an Application to Brain Connectivity.
AB  - Mediation analysis is often used in the behavioral sciences to investigate the
      role of intermediate variables that lie on the causal path between a randomized
      treatment and an outcome variable. Typically, mediation is assessed using
      structural equation models (SEMs), with model coefficients interpreted as causal
      effects. In this article, we present an extension of SEMs to the functional data
      analysis (FDA) setting that allows the mediating variable to be a continuous
      function rather than a single scalar measure, thus providing the opportunity to
      study the functional effects of the mediator on the outcome. We provide
      sufficient conditions for identifying the average causal effects of the
      functional mediators using the extended SEM, as well as weaker conditions under
      which an instrumental variable estimand may be interpreted as an effect. The
      method is applied to data from a functional magnetic resonance imaging (fMRI)
      study of thermal pain that sought to determine whether activation in certain
      brain regions mediated the effect of applied temperature on self-reported pain.
      Our approach provides valuable information about the timing of the mediating
      effect that is not readily available when using the standard nonfunctional
      approach. To the best of our knowledge, this work provides the first application
      of causal inference to the FDA framework.

PMID- 25076801
TI  - Rebuilding TRUST: A Community, Multi-Agency, State, and University Partnership to
      Improve Behavioral Health Care for American Indian Youth, their Families, and
      Communities.
AB  - American Indian/Alaska Native youth represent the strength and survival of many
      Nations and Tribes. However, the aftermath of colonialism has resulted in
      numerous health disparities and challenges for Native youth, including the
      highest rate of suicide in the United States. With the aims of elucidating the
      causes of behavioral health disparities, eliminating them, and improving
      behavioral health care for Native youth, a partnership of providers, community
      members, and university faculty and staff completed a comprehensive literature
      review; conducted advisory meetings with 71 American Indian youth, parents, and
      elders; surveyed 25 service providers; and engaged in ongoing consultation with
      traditional practitioners. Results from the multiple sources were synthesized and
      are reported with 20 policy, provider, and research recommendations that
      recognize the importance of moving beyond exclusive reliance on western models of
      care and that seek to foster transformation of individuals, families,
      communities, behavioral health service systems of care, and social structures.

PMID- 25076803
TI  - Will they like me? Adolescents' emotional responses to peer evaluation.
AB  - Relative to children and adults, adolescents are highly focused on being
      evaluated by peers. This increased attention to peer evaluation has implications
      for emotion regulation in adolescence, but little is known about the
      characteristics of the evaluatee and evaluator that influence emotional reactions
      to evaluative outcomes. The present study used a computer-based social evaluation
      task to examine predictors of adolescents' emotional responses to feedback from
      unknown peers. Nine-to-seventeen-year-olds (N = 36) completed the "chatroom task"
      and indicated the degree to which each peer would be interested in interacting
      with them and how good they felt after receiving acceptance and rejection
      feedback from peers. We examined whether adolescents' age and gender impacted
      their emotional responses to being accepted or rejected by peers of different age
      groups (i.e., early or middle adolescence) and genders. We also tested whether
      expectations about peers' interest was associated with variability in
      adolescents' emotional responses to the evaluative outcome. Upon being accepted
      by middle adolescent male peers, females in the middle relative to early years of
      adolescence reported greater well-being, whereas males reported similar levels of
      well-being regardless of their own age. Following acceptance from middle
      adolescent female peers, females reported greater well-being than males.
      Adolescents with high expectations for being liked by peers felt better after
      being accepted versus rejected relative to those with low expectations. For
      adolescents with low expectations, acceptance and rejection were associated with
      similar levels of well-being. Adolescents' emotional responses to peer evaluation
      are influenced by specific individual characteristics and antecedent preparation
      for evaluation that may serve an emotion regulatory purpose.

PMID- 25076804
TI  - Dopaminergic therapy in aphasia.
AB  - BACKGROUND: The dopaminergic system is involved in a wide range of cognitive
      functions including motor control, reward, memory, attention, problem-solving and
      learning. This has stimulated interest in investigating the potential of
      dopaminergic drugs as cognitive enhancers in aphasic patients. AIM: To discuss
      the evidence for the use of dopaminergic agents in patients with aphasia.
      Levodopa (L-dopa) and the dopamine agonist bromocriptine are the two drugs that
      have been trialled to date. We discuss, in some detail, the 15 studies that have
      been published on this topic from the first case report in 1988 to the present
      (2012), and assess the evidence from each. MAIN CONTRIBUTION: In addition to
      summarising the effectiveness of the drugs that have been tried, we examine the
      possible cognitive mechanisms by which dopaminergic drugs may act on language
      function and aphasia recovery. Given the wide range of dopaminergic drugs, it is
      surprising that such a narrow range has been trialled in aphasic patients.
      Important lessons are to be learned from published studies and we discuss optimal
      trial designs to help guide future work. CONCLUSIONS: The evidence for the
      efficacy of dopaminergic agents in aphasia therapy is mixed. Further trials with
      better tolerated agents are required. Optimal trial designs with appropriate
      control groups or blocks should be used. The mechanism of action is unclear, but
      at the cognitive level the evidence points towards either (re)learning of word
      forms or their improved retrieval.

PMID- 25076805
TI  - New insights into diversity and selectivity of trentepohlialean lichen
      photobionts from the extratropics.
AB  - Aerial green algae of Trentepohliaceae can form conspicuous free-living colonies,
      be parasites of plants or photobionts of lichen-forming ascomycetes. So far,
      their diversity in temperate regions is still poorly known as it has been mostly
      studied by phenotypic approaches only. We present new insights in the
      phylogenetic relationships of lichenized representatives from temperate and
      Mediterranean parts of Europe by analysis of 18S rRNA and rbcL gene fragments,
      and nuclear ITS sequence data. For this purpose we isolated the trentepohlialean
      photobionts from lichens representing different genera. Algal cultures from
      lichenized and free-living Trentepohliaceae were used to design new primers for
      amplification of the marker loci. We constructed a phylogenetic hypothesis to
      reveal the phylogenetic placements of lichenized lineages with 18S rRNA and rbcL
      sequences. ITS variation among the clades was substantial and did not allow
      including them in the general phylogenetic assessment, yet ITS appears to be a
      promising marker for DNA-barcoding approaches. Specific algae were found in
      particular lichen but the overall diversity of photobionts was limited. The
      multilocus tree does not support the current morphological classification of
      genera in Trentepohliaceae, suggesting that morphology is more variable than
      previously thought in this group of algae.

PMID- 25076806
TI  - The Development of a School-Based Measure of Child Mental Health.
AB  - Early detection of child mental health problems in schools is critical for
      implementing strategies for prevention and intervention. The development of an
      effective measure of mental health and well-being for this context must be both
      empirically sound and practically feasible. This study reports the initial
      validation of a brief self-report measure for child mental health suitable for
      use with children as young as 8 years old ("Me & My School" [M&MS]). After factor
      analysis, and studies of measurement invariance, 2 subscales emerged: emotional
      difficulties and behavioral difficulties. These 2 subscales were highly
      correlated with corresponding constructs of the Strengths and Difficulties
      Questionnaire (SDQ) and showed correlations with attainment, deprivation, and
      educational needs similar to ones obtained between these demographic measures and
      the SDQ. Results suggest that this school-based self-report measure is
      psychometrically sound, and has the potential of contributing to school mental
      health surveys, evaluation of interventions, and recognition of mental health
      problems within schools.

PMID- 25076807
TI  - Knowledge of and Attitudes Towards Behavioral Health Services Among Older Youth
      in the Foster Care System.
AB  - This study examined knowledge of and attitudes toward services among 268 17-year
      olds with psychiatric diagnoses preparing to exit foster care. A structured
      interview assessed knowledge of services with vignette scenarios and attitudes
      with a standardized scale. Descriptive statistics described the extent of
      knowledge and attitudes among this population and regression analyses examined
      predictors of these dimensions of literacy. Most youth suggested a help source,
      but responses often lacked specificity. Gender and depression were the strongest
      predictors of knowledge and attitudes, respectively. Knowing which aspects of
      literacy are low, and for whom, can inform education efforts to improve access to
      care in adulthood.

PMID- 25076808
TI  - Accidental death and the rule of joint and several liability.
AB  - Most U.S. states have enacted JSL reform, the move from a regime of joint and
      several liability (JSL) that allows plaintiffs to claim full recovery from any
      one of multiple defendants to one where defendants are held liable only for the
      harm they cause. Contrary to previous theoretical work, we show that JSL reform
      can increase precaution by judgment proof agent by giving "deep pockets" an
      incentive to reduce their own liability by bringing judgment-proof agents into
      court. This result can help explain our empirical findings showing that JSL
      reform reduces death rates (and hence increase precaution) for many types of
      accidents. Together, these results highlight the role that litigation costs and
      judgment-proof agents play in the functioning of the American tort system.

PMID- 25076809
TI  - Application of high-strength biodegradable polyurethanes containing different
      ratios of biobased isomannide and poly (epsilon-caprolactone) diol.
AB  - Biodegradable-biocompatible polyurethanes were prepared with fixed hexamethylene
      diisocyanate and varying ratios of isomannide and poly(epsilon-caprolactone) diol
      using a simple one-step polymerization without a catalyst. The polyurethane
      structures were confirmed by 1H-nuclear magnetic resonance, Fourier transform
      infrared spectroscopy, and gel permeation chromatography. The glass transition
      temperatures were determined by thermal analysis to be between 25 degrees C and
      30 degrees C. Degradation tests performed at 37 degrees C in phosphate buffer
      produced mass losses of 5%-10% after 8 weeks. After 5 days of culture, using
      osteoblastic cells, the relative cell number on all the polyurethane films was
      only slightly lower than that of an optimized tissue culture plastic. These
      polymers offer significant promise with a simplistic synthesis and controlled
      degradation.

PMID- 25076810
TI  - The New Demographic Transition: Most Gains in Life Expectancy Now Realized Late
      in Life.
AB  - The share of increases in life expectancy realized after age 65 was only about 20
      percent at the beginning of the 20th century for the US and 16 other countries at
      comparable stages of development; but that share was close to 80 percent by the
      dawn of the 21st century, and is almost certainly approaching 100 percent
      asymptotically. This new demographic transition portends a diminished survival
      effect on working life. For high-income countries at the forefront of the
      longevity transition, expected lifetime labor force participation as a percent of
      life expectancy is declining. Innovative policies are needed if societies wish to
      preserve a positive relationship running from increasing longevity to greater
      prosperity.

PMID- 25076812
TI  - Directional biases in phylogenetic structure quantification: a Mediterranean case
      study.
AB  - Recent years have seen an increasing effort to incorporate phylogenetic
      hypotheses to the study of community assembly processes. The incorporation of
      such evolutionary information has been eased by the emergence of specialized
      software for the automatic estimation of partially resolved supertrees based on
      published phylogenies. Despite this growing interest in the use of phylogenies in
      ecological research, very few studies have attempted to quantify the potential
      biases related to the use of partially resolved phylogenies and to branch length
      accuracy, and no work has examined how tree shape may affect inference of
      community phylogenetic metrics. In this study, using a large plant community and
      elevational dataset, we tested the influence of phylogenetic resolution and
      branch length information on the quantification of phylogenetic structure; and
      also explored the impact of tree shape (stemminess) on the loss of accuracy in
      phylogenetic structure quantification due to phylogenetic resolution. For this
      purpose, we used 9 sets of phylogenetic hypotheses of varying resolution and
      branch lengths to calculate three indices of phylogenetic structure: the mean
      phylogenetic distance (NRI), the mean nearest taxon distance (NTI) and
      phylogenetic diversity (stdPD) metrics. The NRI metric was the less sensitive to
      phylogenetic resolution, stdPD showed an intermediate sensitivity, and NTI was
      the most sensitive one; NRI was also less sensitive to branch length accuracy
      than NTI and stdPD, the degree of sensitivity being strongly dependent on the
      dating method and the sample size. Directional biases were generally towards type
      II errors. Interestingly, we detected that tree shape influenced the accuracy
      loss derived from the lack of phylogenetic resolution, particularly for NRI and
      stdPD. We conclude that well-resolved molecular phylogenies with accurate branch
      length information are needed to identify the underlying phylogenetic structure
      of communities, and also that sensitivity of phylogenetic structure measures to
      low phylogenetic resolution can strongly differ depending on phylogenetic tree
      shape.

PMID- 25076813
TI  - Linear-scaling quantum calculations using non-orthogonal localized molecular
      orbitals.
AB  - An absolute energy minimum variational principle is used for carrying out linear
      scaling calculations with non-orthogonal localized orbitals. Compared with
      results based on orthogonal localized molecular orbitals, the method is shown to
      give significantly more accurate results when the localized molecular orbitals
      are allowed to be non-orthogonal. This is made possible by introducing a second
      minimization for approximating the inverse overlap matrix. We also show how an
      exact line search may be used efficiently with the conjugate gradient method for
      minimizing the energy functional.

PMID- 25076814
TI  - Alexandrium fundyense cyst viability and germling survival in light vs. dark at a
      constant low temperature.
AB  - Both observations and models suggest that large-scale coastal blooms of
      Alexandrium fundyense in the Gulf of Maine are seeded by deep-bottom cyst
      accumulation zones ("seed beds") where cysts germinate from the sediment surface
      or the overlying near-bottom nepheloid layers at water depths exceeding 100 m.
      The germling cells and their vegetative progeny are assumed to be subject to
      mortality while in complete darkness, as they swim to illuminated surface waters.
      To test the validity of this assumption we conducted laboratory investigations of
      cyst viability and the survival of the germling cells and their vegetative
      progeny during prolonged exposure to darkness at a temperature of 6  degrees C,
      simulating the conditions in deep Gulf of Maine waters. We isolated cysts from
      bottom sediments collected in the Gulf of Maine under low red light and incubated
      them in 96-well tissue culture-plates in culture medium under a 10:14 h
      light:dark cycle and under complete darkness. Cyst viability was high, with
      excystment frequency reaching 90% in the illuminated treatment after 30 days and
      in the dark treatment after 50 days. Average germination rates were 0.062 and
      0.038 d-1 for light and dark treatments, respectively. The dark treatment showed
      an approximately 2-week time lag in maximum germination rates compared to the
      light treatment. Survival of germlings was considerably lower in the dark
      treatment. In the light treatments, 47% of germinated cysts produced germlings
      that were able to survive for 7 days and produce vegetative progeny, i.e., there
      were live cells in the well along with an empty cyst at least once during the
      experiment. In the dark treatments 12% of the cysts produced germlings that were
      able to survive for the same length of time. When dark treatments are scaled to
      take into account non-darkness related mortality, approximately 28% of the cysts
      produced germlings that were able to survive for at least 7 days. Even though
      cysts are able to germinate in darkness, the lack of illumination considerably
      reduces survival rate of germling cells. In addition to viability of cysts in
      surface sediments and the near-bottom nepheloid layer, survivability of germling
      cells and their vegetative progeny at aphotic depths is an important
      consideration in assessing the quantitative role of deep-coastal cyst seed beds
      in bloom formation.

PMID- 25076811
TI  - Polyelectrolyte Multilayer Assemblies on Materials Surfaces: From Cell Adhesion
      to Tissue Engineering.
AB  - Controlling the bulk and surface properties of materials is a real challenge for
      bioengineers working in the fields of biomaterials, tissue engineering and
      biophysics. The layer-by-layer (LbL) deposition method, introduced 20 years ago,
      consists in the alternate adsorption of polyelectrolytes that self-organize on
      the material's surface, leading to the formation of polyelectrolyte multilayer
      (PEM) films.1 Because of its simplicity and versatility, the procedure has led to
      considerable developments of biological applications within the past 5 years. In
      this review, we focus our attention on the design of PEM films as surface
      coatings for applications in the field of physical properties that have emerged
      as being key points in relation to biological processes. The numerous
      possibilities for adjusting the chemical, physical, and mechanical properties of
      PEM films have fostered studies on the influence of these parameters on cellular
      behaviors. Importantly, PEM have emerged as a powerful tool for the
      immobilization of biomolecules with preserved bioactivity.

PMID- 25076815
TI  - Categorizing the severity of paralytic shellfish poisoning outbreaks in the Gulf
      of Maine for forecasting and management.
AB  - Development of forecasting systems for harmful algal blooms (HABs) has been a
      long-standing research and management goal. Significant progress has been made in
      the Gulf of Maine, where seasonal bloom forecasts are now being issued annually
      using Alexandrium fundyense cyst abundance maps and a population dynamics model
      developed for that organism. Thus far, these forecasts have used terms such as
      "significant", "moderately large" or "moderate" to convey the extent of
      forecasted paralytic shellfish poisoning (PSP) outbreaks. In this study,
      historical shellfish harvesting closure data along the coast of the Gulf of Maine
      were used to derive a series of bloom severity levels that are analogous to those
      used to define major storms like hurricanes or tornados. Thirty-four years of PSP
      related shellfish closure data for Maine, Massachusetts and New Hampshire were
      collected and mapped to depict the extent of coastline closure in each year. Due
      to fractal considerations, different methods were explored for measuring length
      of coastline closed. Ultimately, a simple procedure was developed using arbitrary
      straight-line segments to represent specific sections of the coastline. This
      method was consistently applied to each year's PSP toxicity closure map to
      calculate the total length of coastline closed. Maps were then clustered together
      statistically to yield distinct groups of years with similar characteristics. A
      series of categories or levels was defined ("Level 1: Limited", "Level 2:
      Moderate", and "Level 3: Extensive") each with an associated range of expected
      coastline closed, which can now be used instead of vague descriptors in future
      forecasts. This will provide scientifically consistent and simply defined
      information to the public as well as resource managers who make decisions on the
      basis of the forecasts.

PMID- 25076816
TI  - PSP toxin levels and plankton community composition and abundance in size
      fractionated vertical profiles during spring/summer blooms of the toxic
      dinoflagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank,
      2007, 2008, and 2010: 1. Toxin levels.
AB  - As part of the NOAA ECOHAB funded Gulf of Maine Toxicity (GOMTOX) project, we
      determined Alexandrium fundyense abundance, paralytic shellfish poisoning (PSP)
      toxin composition, and concentration in quantitatively-sampled size-fractionated
      (20-64, 64-100, 100-200, 200-500, and > 500 MUm) particulate water samples, and
      the community composition of potential grazers of A. fundyense in these size
      fractions, at multiple depths (typically 1, 10, 20 m, and near-bottom) during 10
      large-scale sampling cruises during the A. fundyense bloom season (May-August) in
      the coastal Gulf of Maine and on Georges Bank in 2007, 2008, and 2010. Our
      findings were as follows: (1) when all sampling stations and all depths were
      summed by year, the majority (94% +/- 4%) of total PSP toxicity was contained in
      the 20-64 MUm size fraction; (2) when further analyzed by depth, the 20-64 MUm
      size fraction was the primary source of toxin for 97% of the stations and depths
      samples over three years; (3) overall PSP toxin profiles were fairly consistent
      during the three seasons of sampling with gonyautoxins (1, 2, 3, and 4)
      dominating (90.7% +/- 5.5%), followed by the carbamate toxins saxitoxin (STX) and
      neosaxitoxin (NEO) (7.7% +/- 4.5%), followed by n-sulfocarbamoyl toxins (C1 and
      2, GTX5) (1.3% +/- 0.6%), followed by all decarbamoyl toxins (dcSTX, dcNEO,
      dcGTX2&3) (< 1%), although differences were noted between PSP toxin compositions
      for nearshore coastal Gulf of Maine sampling stations compared to offshore
      Georges Bank sampling stations for 2 out of 3 years; (4) surface cell counts of
      A. fundyense were a fairly reliable predictor of the presence of toxins
      throughout the water column; and (5) nearshore surface cell counts of A.
      fundyense in the coastal Gulf of Maine were not a reliable predictor of A.
      fundyense populations offshore on Georges Bank for 2 out of the 3 years sampled.

PMID- 25076817
TI  - A note on a nonparametric regression test through penalized splines.
AB  - We examine a test of a nonparametric regression function based on penalized
      spline smoothing. We show that, similarly to a penalized spline estimator, the
      asymptotic power of the penalized spline test falls into a small- K or a large-K
      scenarios characterized by the number of knots K and the smoothing parameter.
      However, the optimal rate of K and the smoothing parameter maximizing power for
      testing is different from the optimal rate minimizing the mean squared error for
      estimation. Our investigation reveals that compared to estimation, some under
      smoothing may be desirable for the testing problems. Furthermore, we compare the
      proposed test with the likelihood ratio test (LRT). We show that when the true
      function is more complicated, containing multiple modes, the test proposed here
      may have greater power than LRT. Finally, we investigate the properties of the
      test through simulations and apply it to two data examples.

PMID- 25076818
TI  - Correlation of contrast-enhanced MR images with the histopathology of minimally
      invasive thermal and cryoablation cancer treatments in normal dog prostates.
AB  - Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery
      of minimally invasive cancer treatments such as high intensity ultrasound (HUS)
      and cryoablation. We use an acute dog prostate model to correlate lesion
      histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the
      radiologists in real time interpretation of in vivo lesion boundaries and pre
      existing lesions. Following thermal or cryo treatments, prostate glands are
      removed, sliced, stained with the vital dye triphenyl tetrazolium chloride,
      photographed, fixed and processed in oversized blocks for routine microscopy.
      Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the
      various lesions traced using annotation software, and digital images compared to
      CE MR images. Histologically, HUS results in discrete lesions characterized by a
      "heat-fixed" zone, in which glands subjected to the highest temperatures are
      minimally altered, surrounded by a rim or "transition zone" composed of severely
      fragmented, necrotic glands, interstitial edema and vascular congestion. The
      "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears
      as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear
      similar to thermally induced lesions, yet the histopathology is significantly
      different. Glands subjected to prolonged freezing appear totally disrupted,
      coagulated and hemorrhagic, while less intensely frozen glands along the lesion
      edge are partially fragmented and contain apoptotic cells. In conclusion, thermal
      and cryo-induced lesions, as well as certain pre-existing lesions (cystic
      hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI
      profiles, useful for treatment and diagnostic purposes.

PMID- 25076819
TI  - Ultrasound interstitial thermal therapy (USITT) for the treatment of uterine
      myomas.
AB  - Uterine myomas (fibroids) are the most common pelvic tumors occurring in women,
      and are the leading cause of hysterectomy. Symptoms can be severe, and
      traditional treatments involve either surgical removal of the uterus
      (hysterectomy), or the fibroids (myomectomy). Interstitial ultrasound
      technologies have demonstrated potential for hyperthermia and high temperature
      thermal therapy in the treatment of benign and malignant tumors. These ultrasound
      devices offer favorable energy penetration allowing large volumes of tissue to be
      treated in short periods of time, as well as axial and angular control of heating
      to conform thermal treatment to a targeted tissue, while protecting surrounding
      tissues from thermal damage. The goal of this project is to evaluate interstitial
      ultrasound for controlled thermal coagulation of fibroids. Multi-element
      applicators were fabricated using tubular transducers, some of which were
      sectored to produce 180 degrees  directional heating patterns, and integrated
      with water cooling. Human uterine fibroids were obtained after routine
      myomectomies, and instrumented with thermocouples spaced at 0.5, 1.0, 1.5, 2.0,
      2.5 and 3.0 cm from the applicator. Power levels ranging from 8-15 W per element
      were applied for up to 15 minute heating periods. Results demonstrated that
      therapeutic temperatures >50 degrees  C and cytotoxic thermal doses (t43)
      extended beyond 2 cm radially from the applicator (>4 cm diameter). It is
      anticipated that this system will make a significant contribution toward the
      treatment of uterine fibroids.

PMID- 25076820
TI  - Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of
      locally advanced cancer of the prostate and cervix.
AB  - A clinical treatment delivery platform has been developed and is being evaluated
      in a clinical pilot study for providing 3D controlled hyperthermia with catheter
      based ultrasound applicators in conjunction with high dose rate (HDR)
      brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial
      control of heating in both angle and length of the devices, with enhanced radial
      penetration of heating compared to other hyperthermia technologies. Interstitial
      and endocavity ultrasound devices have been developed specifically for applying
      hyperthermia within HDR brachytherapy implants during radiation therapy in the
      treatment of cervix and prostate. A pilot study of the combination of catheter
      based ultrasound with HDR brachytherapy for locally advanced prostate and
      cervical cancer has been initiated, and preliminary results of the performance
      and heating distributions are reported herein. The treatment delivery platform
      consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring
      system. Controlling software can monitor and regulate frequency and power to each
      transducer section as required during the procedure. Interstitial applicators
      consist of multiple transducer sections of 2-4 cm length * 180 deg and 3-4 cm *
      360 deg. heating patterns to be inserted in specific placed 13g implant
      catheters. The endocavity device, designed to be inserted within a 6 mm OD
      plastic tandem catheter within the cervix, consists of 2-3 transducers * dual 180
      or 360 deg sectors. 3D temperature based treatment planning and optimization is
      dovetailed to the HDR optimization based planning to best configure and position
      the applicators within the catheters, and to determine optimal base power levels
      to each transducer section. To date we have treated eight cervix implants and six
      prostate implants. 100 % of treatments achieved a goal of >60 min duration, with
      therapeutic temperatures achieved in all cases. Thermal dosimetry within the
      hyperthermia target volume (HTV) and clinical target volume (CTV) are reported.
      Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic
      temperature coverage of the target volume within the prostate or cervix while
      sparing surrounding more sensitive regions. (NIHR01CA122276).

PMID- 25076821
TI  - A Fully Actuated Robotic Assistant for MRI-Guided Prostate Biopsy and
      Brachytherapy.
AB  - Intra-operative medical imaging enables incorporation of human experience and
      intelligence in a controlled, closed-loop fashion. Magnetic resonance imaging
      (MRI) is an ideal modality for surgical guidance of diagnostic and therapeutic
      procedures, with its ability to perform high resolution, real-time, high soft
      tissue contrast imaging without ionizing radiation. However, for most current
      image-guided approaches only static pre-operative images are accessible for
      guidance, which are unable to provide updated information during a surgical
      procedure. The high magnetic field, electrical interference, and limited access
      of closed-bore MRI render great challenges to developing robotic systems that can
      perform inside a diagnostic high-field MRI while obtaining interactively updated
      MR images. To overcome these limitations, we are developing a piezoelectrically
      actuated robotic assistant for actuated percutaneous prostate interventions under
      real-time MRI guidance. Utilizing a modular design, the system enables coherent
      and straight forward workflow for various percutaneous interventions, including
      prostate biopsy sampling and brachytherapy seed placement, using various needle
      driver configurations. The unified workflow compromises: 1) system hardware and
      software initialization, 2) fiducial frame registration, 3) target selection and
      motion planning, 4) moving to the target and performing the intervention (e.g.
      taking a biopsy sample) under live imaging, and 5) visualization and
      verification. Phantom experiments of prostate biopsy and brachytherapy were
      executed under MRI-guidance to evaluate the feasibility of the workflow. The
      robot successfully performed fully actuated biopsy sampling and delivery of
      simulated brachytherapy seeds under live MR imaging, as well as precise delivery
      of a prostate brachytherapy seed distribution with an RMS accuracy of 0.98mm.

PMID- 25076822
TI  - Quantitative evaluation of multi-parametric MR imaging marker changes post-laser
      interstitial ablation therapy (LITT) for epilepsy.
AB  - Laser-induced interstitial thermal therapy (LITT) has recently emerged as a new,
      less invasive alternative to craniotomy for treating epilepsy; which allows for
      focussed delivery of laser energy monitored in real time by MRI, for precise
      removal of the epileptogenic foci. Despite being minimally invasive, the effects
      of laser ablation on the epileptogenic foci (reflected by changes in MR imaging
      markers post-LITT) are currently unknown. In this work, we present a quantitative
      framework for evaluating LITT-related changes by quantifying per-voxel changes in
      MR imaging markers which may be more reflective of local treatment related
      changes (TRC) that occur post-LITT, as compared to the standard volumetric
      analysis which involves monitoring a more global volume change across pre-, and
      post-LITT MRI. Our framework focuses on three objectives: (a) development of
      temporal MRI signatures that characterize TRC corresponding to patients with
      seizure freedom by comparing differences in MR imaging markers and monitoring
      them over time, (b) identification of the optimal time point when early LITT
      induced effects (such as edema and mass effect) subside by monitoring TRC at
      subsequent time-points post-LITT, and (c) identification of contributions of
      individual MRI protocols towards characterizing LITT-TRC for epilepsy by
      identifying MR markers that change most dramatically over time and employ
      individual contributions to create a more optimal weighted MP-MRI temporal
      profile that can better characterize TRC compared to any individual imaging
      marker. A cohort of patients were monitored at different time points post-LITT
      via MP-MRI involving T1-w, T2-w, T2-GRE, T2-FLAIR, and apparent diffusion
      coefficient (ADC) protocols. Post affine registration of individual MRI protocols
      to a reference MRI protocol pre-LITT, differences in individual MR markers are
      computed on a per-voxel basis, at different time-points with respect to baseline
      (pre-LITT) MRI as well as across subsequent time-points. A time-dependent MRI
      profile corresponding to successful (seizure-free) is then created that captures
      changes in individual MR imaging markers over time. Our preliminary analysis on
      two patient studies suggests that (a) LITT related changes (attributed to
      swelling and edema) appear to subside within 4-weeks post-LITT, (b) ADC may be
      more sensitive for evaluating early TRC (upto 3-months), and T1-w may be more
      sensitive in evaluating early delayed TRC (1-month, 3-months), while T2-w and T2
      FLAIR appeared to be more sensitive in identifying late TRC (around 6-months post
      LITT) compared to the other MRI protocols under evaluation. T2-GRE was found to
      be only nominally sensitive in identifying TRC at any follow-up time-point post
      LITT. The framework presented in this work thus serves as an important precursor
      to a comprehensive treatment evaluation framework that can be used to identify
      sensitive MR markers corresponding to patient response (seizure-freedom or
      seizure recurrence), with an ultimate objective of making prognostic predictions
      about patient outcome post-LITT.

PMID- 25076823
TI  - Peripheral Quantitative CT (pQCT) Using a Dedicated Extremity Cone-Beam CT
      Scanner.
AB  - PURPOSE: We describe the initial assessment of the peripheral quantitative CT
      (pQCT) imaging capabilities of a cone-beam CT (CBCT) scanner dedicated to
      musculoskeletal extremity imaging. The aim is to accurately measure and quantify
      bone and joint morphology using information automatically acquired with each CBCT
      scan, thereby reducing the need for a separate pQCT exam. METHODS: A prototype
      CBCT scanner providing isotropic, sub-millimeter spatial resolution and soft
      tissue contrast resolution comparable or superior to standard multi-detector CT
      (MDCT) has been developed for extremity imaging, including the capability for
      weight-bearing exams and multi-mode (radiography, fluoroscopy, and volumetric)
      imaging. Assessment of pQCT performance included measurement of bone mineral
      density (BMD), morphometric parameters of subchondral bone architecture, and
      joint space analysis. Measurements employed phantoms, cadavers, and patients from
      an ongoing pilot study imaged with the CBCT prototype (at various acquisition,
      calibration, and reconstruction techniques) in comparison to MDCT (using pQCT
      protocols for analysis of BMD) and micro-CT (for analysis of subchondral
      morphometry). RESULTS: The CBCT extremity scanner yielded BMD measurement within
      +/-2-3% error in both phantom studies and cadaver extremity specimens.
      Subchondral bone architecture (bone volume fraction, trabecular thickness, degree
      of anisotropy, and structure model index) exhibited good correlation with gold
      standard micro-CT (error ~5%), surpassing the conventional limitations of spatial
      resolution in clinical MDCT scanners. Joint space analysis demonstrated the
      potential for sensitive 3D joint space mapping beyond that of qualitative
      radiographic scores in application to non-weight-bearing versus weight-bearing
      lower extremities and assessment of phalangeal joint space integrity in the upper
      extremities. CONCLUSION: The CBCT extremity scanner demonstrated promising
      initial results in accurate pQCT analysis from images acquired with each CBCT
      scan. Future studies will include improved x-ray scatter correction and image
      reconstruction techniques to further improve accuracy and to correlate pQCT
      metrics with known pathology.

PMID- 25076825
TI  - High-Performance Soft-Tissue Imaging in Extremity Cone-Beam CT.
AB  - PURPOSE: Clinical performance studies of an extremity cone-beam CT (CBCT) system
      indicate excellent bone visualization, but point to the need for improvement of
      soft-tissue image quality. To this end, a rapid Monte Carlo (MC) scatter
      correction is proposed, and Penalized Likelihood (PL) reconstruction is evaluated
      for noise management. METHODS: The accelerated MC scatter correction involved
      fast MC simulation with low number of photons implemented on a GPU (107
      photons/sec), followed by Gaussian kernel smoothing in the detector plane and
      across projection angles. PL reconstructions were investigated for reduction of
      imaging dose for projections acquired at ~2 mGy. RESULTS: The rapid scatter
      estimation yielded root-mean-squared-errors of scatter projections of ~15% of
      peak scatter intensity for 5.106 photons/projection (runtime ~0.5 sec/projection)
      and 25% improvement in fat-muscle contrast in reconstructions of a cadaveric
      knee. PL reconstruction largely restored soft-tissue visualization at 2 mGy dose
      to that of 10 mGy FBP image. CONCLUSION: The combination of rapid (5-10
      minutes/scan) MC-based, patient-specific scatter correction and PL reconstruction
      offers an important means to overcome the current limitations of extremity CBCT
      in soft-tissue imaging.

PMID- 25076824
TI  - Regulatory conformational changes of the epsilon subunit in single FRET-labeled
      FoF1-ATP synthase.
AB  - Subunit epsilon is an intrinsic regulator of the bacterial FoF1-ATP synthase, the
      ubiquitous membrane-embedded enzyme that utilizes a proton motive force in most
      organisms to synthesize adenosine triphosphate (ATP). The C-terminal domain of
      epsilon can extend into the central cavity formed by the alpha and beta subunits,
      as revealed by the recent X-ray structure of the F1 portion of the Escherichia
      coli enzyme. This insertion blocks the rotation of the central gamma subunit and,
      thereby, prevents wasteful ATP hydrolysis. Here we aim to develop an experimental
      system that can reveal conditions under which epsilon inhibits the holoenzyme
      FoF1-ATP synthase in vitro. Labeling the C-terminal domain of epsilon and the
      gamma subunit specifically with two different fluorophores for single-molecule
      Forster resonance energy transfer (smFRET) allowed monitoring of the conformation
      of epsilon in the reconstituted enzyme in real time. New mutants were made for
      future three-color smFRET experiments to unravel the details of regulatory
      conformational changes in epsilon.

PMID- 25076826
TI  - Evaluating the Predictive Power of Multivariate Tensor-based Morphometry in
      Alzheimers Disease Progression via Convex Fused Sparse Group Lasso.
AB  - Prediction of Alzheimers disease (AD) progression based on baseline measures
      allows us to understand disease progression and has implications in decisions
      concerning treatment strategy. To this end we combine a predictive multi-task
      machine learning method1 with novel MR-based multivariate morphometric surface
      map of the hippocampus2 to predict future cognitive scores of patients. Previous
      work by Zhou et al.1 has shown that a multi-task learning framework that performs
      prediction of all future time points (or tasks) simultaneously can be used to
      encode both sparsity as well as temporal smoothness. They showed that this can be
      used in predicting cognitive outcomes of Alzheimers Disease Neuroimaging
      Initiative (ADNI) subjects based on FreeSurfer-based baseline MRI features, MMSE
      score demographic information and ApoE status. Whilst volumetric information may
      hold generalized information on brain status, we hypothesized that hippocampus
      specific information may be more useful in predictive modeling of AD. To this
      end, we applied Shi et al.2s recently developed multivariate tensor-based (mTBM)
      parametric surface analysis method to extract features from the hippocampal
      surface. We show that by combining the power of the multi-task framework with the
      sensitivity of mTBM features of the hippocampus surface, we are able to improve
      significantly improve predictive performance of ADAS cognitive scores 6, 12, 24,
      36 and 48 months from baseline.

PMID- 25076827
TI  - An artifact-robust, shape library-based algorithm for automatic segmentation of
      inner ear anatomy in post-cochlear-implantation CT.
AB  - A cochlear implant (CI) is a device that restores hearing using an electrode
      array that is surgically placed in the cochlea. After implantation, the CI is
      programmed to attempt to optimize hearing outcome. Currently, we are testing an
      image-guided CI programming (IGCIP) technique we recently developed that relies
      on knowledge of relative position of intracochlear anatomy to implanted
      electrodes. IGCIP is enabled by a number of algorithms we developed that permit
      determining the positions of electrodes relative to intra-cochlear anatomy using
      a pre- and a post-implantation CT. One issue with this technique is that it
      cannot be used for many subjects for whom a pre-implantation CT was not acquired.
      Pre-implantation CT has been necessary because it is difficult to localize the
      intra-cochlear structures in post-implantation CTs alone due to the image
      artifacts that obscure the cochlea. In this work, we present an algorithm for
      automatically segmenting intra-cochlear anatomy in post-implantation CTs. Our
      approach is to first identify the labyrinth and then use its position as a
      landmark to localize the intra-cochlea anatomy. Specifically, we identify the
      labyrinth by first approximately estimating its position by mapping a labyrinth
      surface of another subject that is selected from a library of such surfaces and
      then refining this estimate by a standard shape model-based segmentation method.
      We tested our approach on 10 ears and achieved overall mean and maximum errors of
      0.209 and 0.98 mm, respectively. This result suggests that our approach is
      accurate enough for developing IGCIP strategies based solely on post-implantation
      CTs.

PMID- 25076828
TI  - EM-Navigated Catheter Placement for Gynecologic Brachytherapy: An Accuracy Study.
AB  - Gynecologic malignancies, including cervical, endometrial, ovarian, vaginal and
      vulvar cancers, cause significant mortality in women worldwide. The standard care
      for many primary and recurrent gynecologic cancers consists of chemoradiation
      followed by brachytherapy. In high dose rate (HDR) brachytherapy, intracavitary
      applicators and/or interstitial needles are placed directly inside the cancerous
      tissue so as to provide catheters to deliver high doses of radiation. Although
      technology for the navigation of catheters and needles is well developed for
      procedures such as prostate biopsy, brain biopsy, and cardiac ablation, it is
      notably lacking for gynecologic HDR brachytherapy. Using a benchtop study that
      closely mimics the clinical interstitial gynecologic brachytherapy procedure, we
      developed a method for evaluating the accuracy of image-guided catheter
      placement. Future bedside translation of this technology offers the potential
      benefit of maximizing tumor coverage during catheter placement while avoiding
      damage to the adjacent organs, for example bladder, rectum and bowel. In the
      study, two independent experiments were performed on a phantom model to evaluate
      the targeting accuracy of an electromagnetic (EM) tracking system. The procedure
      was carried out using a laptop computer (2.1GHz Intel Core i7 computer, 8GB RAM,
      Windows 7 64-bit), an EM Aurora tracking system with a 1.3mm diameter 6 DOF
      sensor, and 6F (2 mm) brachytherapy catheters inserted through a Syed-Neblett
      applicator. The 3D Slicer and PLUS open source software were used to develop the
      system. The mean of the targeting error was less than 2.9mm, which is comparable
      to the targeting errors in commercial clinical navigation systems.

PMID- 25076829
TI  - Pursuing optimal thresholds to recommend breast biopsy by quantifying the value
      of tomosynthesis.
AB  - A 2% threshold has been traditionally used to recommend breast biopsy in
      mammography. We aim to characterize how the biopsy threshold varies to achieve
      the maximum expected utility (MEU) of tomosynthesis for breast cancer diagnosis.
      A cohort of 312 patients, imaged with standard full field digital mammography
      (FFDM) and digital breast tomosynthesis (DBT), was selected for a reader study.
      Fifteen readers interpreted each patient's images and estimated the probability
      of malignancy using two modes: FFDM versus FFDM + DBT. We generated receiver
      operator characteristic (ROC) curves with the probabilities for all readers
      combined. We found that FFDM+DBT provided improved accuracy and MEU compared with
      FFDM alone. When DBT was included in the diagnosis along with FFDM, the optimal
      biopsy threshold increased to 2.7% as compared with the 2% threshold for FFDM
      alone. While understanding the optimal threshold from a decision analytic
      standpoint will not help physicians improve their performance without additional
      guidance (e.g. decision support to reinforce this threshold), the discovery of
      this level does demonstrate the potential clinical improvements attainable with
      DBT. Specifically, DBT has the potential to lead to substantial improvements in
      breast cancer diagnosis since it could reduce the number of patients recommended
      for biopsy while preserving the maximal expected utility.

PMID- 25076830
TI  - Mapping of ApoE4 Related White Matter Damage using Diffusion MRI.
AB  - ApoliopoproteinE epsilon4 (ApoE-epsilon4) polymorphism is the most well known
      genetic risk factor for developing Alzheimers Disease. The exact mechanism
      through which ApoE epsilon4 increases AD risk is not fully known, but may be
      related to decreased clearance and increased oligomerization of Abeta. By making
      measurements of white matter integrity via diffusion MR and correlating the
      metrics in a voxel-based statistical analysis with ApoE-epsilon4 genotype (whilst
      controlling for vascular risk factor, gender, cognitive status and age) we are
      able to identify changes in white matter associated with carrying an ApoE
      epsilon4 allele. We found potentially significant regions (Puncorrected < 0.05)
      near the hippocampus and the posterior cingulum that were independent of voxels
      that correlated with age or clinical dementia rating (CDR) status suggesting that
      ApoE may affect cognitive decline via a pathway in dependent of normal aging and
      acute insults that can be measured by CDR and Framingham Coronary Risk Score
      (FCRS).

PMID- 25076831
TI  - The Power of Hybrid/Fusion Imaging Metrics in Future PACS Systems: A Case Study
      into the White Matter Hyperintensity Prenumbra using FLAIR and Diffusion MR.
AB  - Most white matter related neurological disease exhibit a large number of White
      Matter Hyperintensities (WMHs) on FLAIR MRI images. However, these lesions are
      not well understood. At the same time, Diffusion MRI has been gaining popularity
      as a powerful method of characterizing White Matter (WM) integrity. This work
      aims to study the behavior of the diffusion signal within the WMH voxels. The
      goal is to develop hybrid MR metrics that leverage information from multiple MR
      acquisitions to solve clinical problems. In our case, we are trying to address
      the WMH penumbra (as defined by Maillard et al 20112) where WMH delineates a foci
      that is more widespread than than the actual damage area presumably due to acute
      inflammation. Our results show that diffusion MR metrics may be able to better
      delineate tissue that is inflamed versus scar tissue but may be less specific to
      lesions than FLAIR. Therefore, a hybrid metric that encodes information from both
      FLAIR and Diffusion MR may yield new and novel imaging information about the
      progression of white matter disease progression. We hope that this work also
      demonstrates how future PACS systems could have image fusion capabilities that
      would be able to leverage information from multiple imaging series to yield new
      and novel imaging contrast.

PMID- 25076832
TI  - Developing a Reporting Guideline for Social and Psychological Intervention
      Trials.
AB  - Social and psychological interventions are often complex. Understanding
      randomized controlled trials (RCTs) of these complex interventions requires a
      detailed description of the interventions tested and the methods used to evaluate
      them; however, RCT reports often omit, or inadequately report, this information.
      Incomplete and inaccurate reporting hinders the optimal use of research, wastes
      resources, and fails to meet ethical obligations to research participants and
      consumers. In this article, we explain how reporting guidelines have improved the
      quality of reports in medicine and describe the ongoing development of a new
      reporting guideline for RCTs: Consolidated Standards of Reporting Trials-SPI (an
      extension for social and psychological interventions). We invite readers to
      participate in the project by visiting our website, in order to help us reach the
      best-informed consensus on these guidelines (http://tinyurl.com/CONSORT-study).

PMID- 25076833
TI  - Trajectories of Depression Symptoms among Older Youths Exiting Foster Care.
AB  - The purpose of this study was to determine the trajectories of depressive
      symptoms as older youths from the foster care system mature while also examining
      the correlates of these trajectories. Data came from a longitudinal study of 404
      youths from the foster care system in Missouri, who were interviewed nine times
      between their 17th and 19th birthdays. Depression was assessed with the
      Depression Outcomes Module and the Diagnostic Interview Schedule for DSM-IV. Data
      best fit a model of three trajectory classes, describing young people (1)
      maintaining low levels of depressive symptoms (never depressed class, 78%), (2)
      with increasing symptoms (increasing class, 6%), and (3) with decreasing symptoms
      (decreasing class, 15%). The increasing depression group was mostly male youths
      who were working or in school; the decreasing class was mostly highly maltreated
      female youths exiting the foster care system from residential care, with low
      levels of employment, and in school. Implications for social work practice are
      discussed.

PMID- 25076834
TI  - Feedback-driven tuning of statistical summary representations.

PMID- 25076835
TI  - Cultural and age differences in beliefs about depression: British Bangladeshis
      vs. British Whites.
AB  - This study examines beliefs about depression as a function of ethnic background
      (British Bangladeshis vs. British Whites) and age. A total of 364 participants
      completed a 65-item questionnaire, containing general questions regarding
      depression and anti-depressive behaviour; the causes of depression, and
      treatments for depression. The hypotheses were broadly supported; there were
      significant interactions between ethnicity and age, which generally revealed an
      increasingly negative attitude towards depression with increasing age amongst
      British Bangladeshis. Older British Bangladeshis believed depression was an
      illness that brought a sense of shame and loss of dignity to the individual and
      his or her family, and they also favoured a lay referral system for sufferers.
      They also had more superstitious beliefs about depression than both younger
      British Bangladeshis and British Whites. A pattern of increasing negativity with
      increasing age was not evident amongst the British Whites, but older individuals
      in both groups tended to believe that depression was not helped by psychological
      intervention. The attitudes towards depression in the young was similar (and
      generally positive) in both ethnic groups. These findings highlight the necessity
      to provide more culturally sensitive and accessible services for migrant
      communities - particularly amongst older individuals.

PMID- 25076836
TI  - Meta-analysis of quantitative trait loci for grain yield and component traits
      under reproductive-stage drought stress in an upland rice population.
AB  - A recombinant inbred population developed from a cross between high-yielding
      lowland rice (Oryza sativa L.) subspecies indica cv. IR64 and upland tropical
      rice subspecies japonica cv. Cabacu was used to identify quantitative trait loci
      (QTLs) for grain yield (GY) and component traits under reproductive-stage drought
      stress. One hundred fifty-four lines were grown in field trials in Indonesia
      under aerobic conditions by giving surface irrigation to field capacity every 4
      days. Water stress was imposed for a period of 15 days during pre-flowering by
      withholding irrigation at 65 days after seeding. Leaf rolling was scored at the
      end of the stress period and eight agronomic traits were evaluated after
      recovery. The population was also evaluated for root pulling force, and a total
      of 201 single nucleotide polymorphism markers were used to construct the
      molecular genetic linkage map and QTL mapping. A QTL for GY under drought stress
      was identified in a region close to the sd1 locus on chromosome 1. QTL meta
      analysis across diverse populations showed that this QTL was conserved across
      genetic backgrounds and co-localized with QTLs for leaf rolling and osmotic
      adjustment (OA). A QTL for percent seed set and grains per panicle under drought
      stress was identified on chromosome 8 in the same region as a QTL for OA
      previously identified in three different populations.

PMID- 25076837
TI  - Allele frequencies in the VRN-A1, VRN-B1 and VRN-D1 vernalization response and
      PPD-B1 and PPD-D1 photoperiod sensitivity genes, and their effects on heading in
      a diverse set of wheat cultivars (Triticum aestivum L.).
AB  - Heading of cereals is determined by complex genetic and environmental factors in
      which genes responsible for vernalization and photoperiod sensitivity play a
      decisive role. Our aim was to use diagnostic molecular markers to determine the
      main allele types in VRN-A1, VRN-B1, VRN-D1, PPD-B1 and PPD-D1 in a worldwide
      wheat collection of 683 genotypes and to investigate the effect of these alleles
      on heading in the field. The dominant VRN-A1, VRN-B1 and VRN-D1 alleles were
      present at a low frequency. The PPD-D1a photoperiod-insensitive allele was
      carried by 57 % of the cultivars and was most frequent in Asian and European
      cultivars. The PPD-B1 photoperiod-insensitive allele was carried by 22 % of the
      genotypes from Asia, America and Europe. Nine versions of the PPD-B1-insensitive
      allele were identified based on gene copy number and intercopy structure. The
      allele compositions in PPD-D1, PPD-B1 and VRN-D1 significantly influenced heading
      and together explained 37.5 % of the phenotypic variance. The role of gene model
      increased to 39.1 % when PPD-B1 intercopy structure was taken into account
      instead of overall PPD-B1 type (sensitive vs. insensitive). As a single
      component, PPD-D1 had the most important role (28.0 % of the phenotypic
      variance), followed by PPD-B1 (12.3 % for PPD-B1_overall, and 15.1 % for PPD
      B1_intercopy) and VRN-D1 (2.2 %). Significant gene interactions were identified
      between the marker alleles within PPD-B1 and between VRN-D1 and the two PPD1
      genes. The earliest heading genotypes were those with the photoperiod-insensitive
      allele in PPD-D1 and PPD-B1, and with the spring allele for VRN-D1 and the winter
      alleles for VRN-A1 and VRN-B1. This combination could only be detected in
      genotypes from Southern Europe and Asia. Late-heading genotypes had the
      sensitivity alleles for both PPD1 genes, regardless of the allelic composition of
      the VRN1 genes. There was a 10-day difference in heading between the earliest and
      latest groups under field conditions.

PMID- 25076838
TI  - Hypersensitive response to Potato virus Y in potato cultivar Sarpo Mira is
      conferred by the Ny-Smira gene located on the long arm of chromosome IX.
AB  - Potato virus Y (PVY, Potyvirus) is the fifth most important plant virus worldwide
      in terms of economic and scientific impact. It infects members of the family
      Solanaceae and causes losses in potato, tomato, tobacco, pepper and petunia
      production. In potato and its wild relatives, two types of resistance genes
      against PVY have been identified. While Ry genes confer symptomless extreme
      resistance, Ny genes cause a hypersensitive response visible as local necrosis
      that may also be able to prevent the virus from spreading under certain
      environmental conditions. The potato cultivar Sarpo Mira originates from Hungary
      and is highly resistant to PVY, although the source of this resistance remains
      unknown. We show that cv. Sarpo Mira reacts with a hypersensitive response
      leading to necrosis after PVYNTN infection in detached leaf, whole plant and
      grafting assays. The hypersensitivity to PVYNTN segregated amongst 140
      individuals of tetraploid progeny of cvs. Sarpo Mira * Maris Piper in a 1:1
      ratio, indicating that it was conferred by a single, dominant gene in simplex.
      Moreover, we identified five DNA markers linked to this trait and located the
      underlying locus (Ny-Smira) to the long arm of potato chromosome IX. This
      position corresponds to the location of the Rychc and Ny-1 genes for PVY
      resistance. A simple PCR marker, located 1 cM from the Ny-Smira gene, can be
      recommended for selection of PVY-resistant progeny of cv. Sarpo Mira.

PMID- 25076839
TI  - Genetic factors responsible for eating and cooking qualities of rice grains in a
      recombinant inbred population of an inter-subspecific cross.
AB  - The eating and cooking qualities of rice grains are the major determinants of
      consumer preference and, consequently, the economic value of a specific rice
      variety. These two qualities are largely determined by the physicochemical
      properties of the starch, i.e. the starch composition, of the rice grain. In our
      study, we determined the genetic factors responsible for the physicochemical
      properties of starch in recombinant inbred lines (RILs) of japonica cv. Tainung
      78 * indica cv. Taichung Sen 17 (TCS 17) cultivated over two crop seasons by
      examining palatability characteristics and several Rapid Viscosity Analyzer (RVA)
      parameters. Thirty-four quantitative trait loci (QTLs), each explaining between
      1.2 and 78.1 % phenotypic variation, were mapped in clusters on eight chromosomes
      in 190 RILs genotyped with 139 markers. Ten pairs of QTLs were detected in the
      two environments, of which seven were in agreement with previous findings,
      suggesting that these QTLs may express stable experimental populations across
      various environments. Waxy (Wx), which controls amylose synthesis, was determined
      to be a primary gene regulating the physicochemical properties of cooked rice
      grains, as indicated by the presence of a major QTL cluster on chromosome 6 and
      by marker regression analysis. Six starch synthesis-related genes (SSRGs) which
      were located in the QTL intervals significantly differed in terms of gene
      expression between the two parents during grain-filling and were important
      genetic factors affecting physicochemical properties. The expression of four
      genes, PUL, ISA2, GBSSI, and SSII-3, was significantly upregulated in TCS 17, and
      this expression was positively correlated with six traits. The effects of the six
      SSRGs and gene interaction depended on genetic background and environment; grain
      quality may be fine tuned by selecting for SBE4 for japonica and PUL for indica.
      We provide valuable information for application in the breeding of new rice
      varieties as daily staple food and for use in industrial manufacturing by marker
      assisted selection.

PMID- 25076840
TI  - Molecular mapping across three populations reveals a QTL hotspot region on
      chromosome 3 for secondary traits associated with drought tolerance in tropical
      maize.
AB  - Identifying quantitative trait loci (QTL) of sizeable effects that are expressed
      in diverse genetic backgrounds across contrasting water regimes particularly for
      secondary traits can significantly complement the conventional drought tolerance
      breeding efforts. We evaluated three tropical maize biparental populations under
      water-stressed and well-watered regimes for drought-related morpho-physiological
      traits, such as anthesis-silking interval (ASI), ears per plant (EPP), stay-green
      (SG) and plant-to-ear height ratio (PEH). In general, drought stress reduced the
      genetic variance of grain yield (GY), while that of morpho-physiological traits
      remained stable or even increased under drought conditions. We detected
      consistent genomic regions across different genetic backgrounds that could be
      target regions for marker-assisted introgression for drought tolerance in maize.
      A total of 203 QTL for ASI, EPP, SG and PEH were identified under both the water
      regimes. Meta-QTL analysis across the three populations identified six
      constitutive genomic regions with a minimum of two overlapping traits. Clusters
      of QTL were observed on chromosomes 1.06, 3.06, 4.09, 5.05, 7.03 and 10.04/06.
      Interestingly, a ~8-Mb region delimited in 3.06 harboured QTL for most of the
      morpho-physiological traits considered in the current study. This region
      contained two important candidate genes viz., zmm16 (MADS-domain transcription
      factor) and psbs1 (photosystem II unit) that are responsible for reproductive
      organ development and photosynthate accumulation, respectively. The genomic
      regions identified in this study partially explained the association of secondary
      traits with GY. Flanking single nucleotide polymorphism markers reported herein
      may be useful in marker-assisted introgression of drought tolerance in tropical
      maize.

PMID- 25076841
TI  - Fine mapping of the tomato yellow leaf curl virus resistance gene Ty-2 on
      chromosome 11 of tomato.
AB  - Resistances to begomoviruses, including bipartite tomato mottle virus and
      monopartite tomato yellow leaf curl virus (TYLCV), have been introgressed to
      cultivated tomato (Solanum lycopersicum) from wild tomato accessions. A major
      gene, Ty-2 from S. habrochaites f. glabratum accession "B6013," that confers
      resistance to TYLCV was previously mapped to a 19-cM region on the long arm of
      chromosome 11. In the present study, approximately 11,000 plants were screened
      and nearly 157 recombination events were identified between the flanking markers
      C2_At1g07960 (82.5 cM, physical distance 51.387 Mb) and T0302 (89 cM, 51.878 Mb).
      Molecular marker analysis of recombinants and TYLCV evaluation of progeny from
      these recombinants localized Ty-2 to an approximately 300,000-bp interval between
      markers UP8 (51.344 Mb) and M1 (51.645 Mb). No recombinants were identified
      between TG36 and C2_At3g52090, a region of at least 115 kb, indicating severe
      recombination suppression in this region. Due to the small interval, fluorescence
      in situ hybridization analysis failed to clarify whether recombination
      suppression is caused by chromosomal rearrangements. Candidate genes predicted
      based on tomato genome annotation were analyzed by RT-PCR and virus-induced gene
      silencing. Results indicate that the NBS gene family present in the Ty-2 region
      is likely not responsible for the Ty-2-conferred resistance and that two
      candidate genes might play a role in the Ty-2-conferred resistance. Several
      markers very tightly linked to the Ty-2 locus are presented and useful for marker
      assisted selection in breeding programs to introgress Ty-2 for begomovirus
      resistance.

PMID- 25076842
TI  - Detecting the oxidative reactivity of nanoparticles: a new protocol for reducing
      artifacts.
AB  - Understanding the oxidative reactivity of nanoparticles (NPs; <100 nm) could
      substantially contribute to explaining their toxicity. We attempted to refine the
      use of 2'7-dichlorodihydrofluorescein (DCFH) to characterize NP generation of
      reactive oxygen species (ROS). Several fluorescent probes have been applied to
      testing oxidative reactivity, but despite DCFH being one of the most popular for
      the detection of ROS, when it has been applied to NPs there have been an
      unexplainably wide variability in results. Without a uniform methodology,
      validating even robust results is impossible. This study, therefore, identified
      sources of conflicting results and investigated ways of reducing occurrence of
      artificial results. Existing techniques were tested and combined (using their
      most desirable features) to form a more reliable method for the measurement of NP
      reactivity in aqueous dispersions. We also investigated suitable sample ranges
      necessary to determine generation of ROS. Specifically, ultrafiltration and time
      resolved scan absorbance spectra were used to study possible optical interference
      when using high sample concentrations. Robust results were achieved at a 5 uM
      DCFH working solution with 0.5 unit/mL horseradish peroxidase (HRP) dissolved in
      ethanol. Sonication in DCFH-HRP working solution provided more stable data with a
      relatively clean background. Optimal particle concentration depends on the type
      of NP and in general was in the ug/mL range. Major reasons for previously
      reported conflicting results due to interference were different experimental
      approaches and NP sample concentrations. The protocol presented here could form
      the basis of a standardized method for applying DCFH to detect generation of ROS
      by NPs.

PMID- 25076843
TI  - Cell therapy with human MSCs isolated from the umbilical cord Wharton jelly
      associated to a PVA membrane in the treatment of chronic skin wounds.
AB  - The healing process of the skin is a dynamic procedure mediated through a complex
      feedback of growth factors secreted by a variety of cells types. Despite the most
      recent advances in wound healing management and surgical procedures, these
      techniques still fail up to 50%, so cellular therapies involving mesenchymal stem
      cells (MSCs) are nowadays a promising treatment of skin ulcers which are a cause
      of high morbidity. The MSCs modulate the inflammatory local response and induce
      cell replacing, by a paracrine mode of action, being an important cell therapy
      for the impaired wound healing. The local application of human MSCs (hMSCs)
      isolated from the umbilical cord Wharton's jelly together with a poly(vinyl
      alcohol) hydrogel (PVA) membrane, was tested to promote wound healing in two dogs
      that were referred for clinical examination at UPVET Hospital, showing non
      healing large skin lesions by the standard treatments. The wounds were
      infiltrated with 1000 cells/ul hMSCs in a total volume of 100 ul per cm(2) of
      lesion area. A PVA membrane was applied to completely cover the wound to prevent
      its dehydration. Both animals after the treatment demonstrated a significant
      progress in skin regeneration with decreased extent of ulcerated areas confirmed
      by histological analysis. The use of Wharton's jelly MSCs associated with a PVA
      membrane showed promising clinical results for future application in the
      treatment of chronic wounds in companion animals and humans. 

PMID- 25076844
TI  - Identification of de novo mutations of Duchenne/Becker muscular dystrophies in
      southern Spain.
AB  - BACKGROUND: Duchenne/Becker muscular dystrophies (DMD/BMD) are X-linked diseases,
      which are caused by a de novo gene mutation in one-third of affected males. The
      study objectives were to determine the incidence of DMD/BMD in Andalusia (Spain)
      and to establish the percentage of affected males in whom a de novo gene mutation
      was responsible. METHODS: Multiplex ligation-dependent probe amplification (MLPA)
      technology was applied to determine the incidence of DMD/BMD in 84 males with
      suspicion of the disease and 106 female relatives. RESULTS: Dystrophin gene exon
      deletion (89.5%) or duplication (10.5%) was detected in 38 of the 84 males by
      MLPA technology; de novo mutations account for 4 (16.7%) of the 24 mother-son
      pairs studied. CONCLUSIONS: MLPA technology is adequate for the molecular
      diagnosis of DMD/BMD and establishes whether the mother carries the molecular
      alteration responsible for the disease, a highly relevant issue for genetic
      counseling.

PMID- 25076845
TI  - Expression of histone deacetylases in diffuse large B-cell lymphoma and its
      clinical significance.
AB  - BACKGROUND: Histone deacetylase inhibitors are a new class of drugs used in
      treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most
      common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell
      lymphomas. In this study, we aimed to determine the expression patterns of
      histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression
      patterns differ among cases, and to assess whether these findings have clinical
      significance. MATERIALS AND METHODS: We selected 91 cases of DLBCL diagnosed at
      St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We
      performed a pathology slide review and collected clinical data including age,
      sex, tumor site, survival time, and mortality. Immunohistochemical analysis was
      performed using primary antibodies for HDACs, including HDAC1 and 2 of class I,
      HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined
      to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and
      high. We assessed correlations between HDAC expression levels and clinical data
      and survival analysis. RESULTS: Of the 91 cases examined, 46 (50.5%) were men and
      45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases
      were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and
      45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining
      was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4;
      however, there was no significant correlation with survival. But nodal lymphoma
      cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high
      nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed
      significantly shorter survival times compared with other cases. CONCLUSIONS: High
      nuclear expression of HDAC2 may play an important role in survival of DLBCL
      patients, especially in those with nodal lymphoma, which is associated with a
      shorter survival time. Our results may have important implications for treatment
      of DLBCL by epigenetic regulation.

PMID- 25076846
TI  - The effects of ABCG2 on the viability, proliferation and paracrine actions of
      kidney side population cells under oxygen-glucose deprivation.
AB  - Bcrp1/ABCG2 is exclusively expressed in side population (SP) cells, however, it
      has not been fully elucidated whether it has an impact on the viability,
      proliferation and paracrine actions in kidney SP cells under oxygen-glucose
      deprivation (OGD) followed by reoxygenation. In this study, we found that 2-h OGD
      did not injure SP cells (sub-lethal OGD) but induced SP cells proliferation 48
      and 72 h after reoxygenation; whereas 4-h OGD markedly injured the cells (lethal
      OGD) and led to apoptosis 24-72 h after reoxygenation. Fumitremorgin C, an
      inhibitor of ABCG2, attenuated both the proliferation and viability of SP cells.
      Sub-lethal and lethal OGD induced the increase in the secretion of vascular
      endothelial growth factor, insulin-like growth factor 1, hepatocyte growth
      factor, and stromal cell-derived factor-1alpha in kidney SP cells, which was
      inhibited by Fumitremorgin C. Collectively, these findings provide evidence for a
      crucial role for the ABCG2 expression in the viability, proliferation and
      paracrine actions of kidney SP cells after OGD. 

PMID- 25076847
TI  - Thickness of palatal masticatory mucosa and its relationship with different
      parameters in Turkish subjects.
AB  - BACKGROUND: The aim of the study was to clinically investigate the mucosal
      variations in different parts of hard palate subject to soft tissue harvesting
      and its relationship with selected parameters in patients with gingival
      recessions. MATERIALS & METHODS: Fifty periodontally healthy, dentate subjects
      (13 males) with gingival recessions were enrolled into the study. After initial
      periodontal therapy they were scheduled for surgical procedures. Palatal
      masticatory mucosa of five teeth was evaluated at five different points from the
      gingival margin and two points on the buccal gingival mucosa were evaluated on
      the day of surgical intervention via bone sounding method. Totally 27 assessments
      were performed for each patient. RESULTS: The overall mean thickness of palatal
      masticatory mucosa (PMM) was 2.55+/-0.49mm. The mean mid-facial gingival
      thickness was 1.11+/-0.39mm. The PMM showed an increase towards the posterior and
      raphe palatina. No difference was observed between genders, and no association of
      body mass index (BMI) and age with PMM was determined. An association was
      observed between the thicknesses of mid-facial gingival and palatal masticatory
      mucosa. CONCLUSION: The thickness of PMM in this study seems to be less than
      other reports possibly due to ethnicity or measurement design. Canine and
      premolar region reveals higher thickness values, and the increase in the tissue
      thickness towards the midline should also been taken into consideration.
      Clinicians planning soft tissue harvesting from the palate should take this
      variation into consideration. In this regard transmucosal probing of the donor
      site may provide valuable information where considerable variation exists.

PMID- 25076848
TI  - Activated hair follicle stem cells and Wnt/beta-catenin signaling involve in
      pathnogenesis of sebaceous neoplasms.
AB  - Sebaceous glands (SGs) undergo cyclic renewal independent of hair follicle stem
      cells (HFSCs) activation while HFSCs have the potential to differentiate into
      sebaceous gland cells, hair follicle and epidermal keratinocytes. Abnormalities
      of sebaceous gland progenitor cells contribute to the development of sebaceous
      neoplasms, but little is known about the role of HFSCs during sebaceous neoplasm
      development. Here, using dimethylbenzanthracene (DMBA) plus 12-o-tetradecanoyl
      phorbol-13-acetate (TPA) treatment developing sebaceous neoplasms (SNs) were
      identified with H&E and Oil red O staining. And then the molecular expression and
      activation of HFSCs and was characterized by immunostaining. Wnt10b/beta-catenin
      signaling molecular which is important for activation of HFSCs were detected by
      immunostaining. We found hair follicle and epidermal cell markers were expressed
      in sebaceous neoplasms. Furthermore, SOX-9 and CD34-positive HFSCs were located
      in the basal layer of sebaceous lobules within the sebaceous neoplasms. Many
      appear to be in an active state. Finally, Wnt10b/beta-catenin signaling was
      activated within the basal cells of sebaceous lobules in the sebaceous neoplasms.
      Collectively, our findings suggest that the abnormal activation of both HFSCs and
      Wnt10b/beta-catenin signaling involves in the development of sebaceous neoplasms.

PMID- 25076850
TI  - Lycopene treatment of prostate cancer cell lines inhibits adhesion and migration
      properties of the cells.
AB  - BACKGROUND: Consumption of lycopene through tomato products has been suggested to
      reduce the risk of prostate cancer. Cellular adhesion and migration are important
      features of cancer progression and therefore a potential target for cancer
      interception. In the present study we have examined the in vitro effect of
      lycopene on these processes. METHODS: Prostate cancer cell lines PC3, DU145 and
      immortalised normal prostate cell line PNT-2 were used. The adhesion assay
      consisted of seeding pre-treated cells onto MatrigelTM, gently removing non
      adherent cells and quantitating the adherent fraction using WST-1. Migratory
      potential was assessed using ibidiTM migration chamber inserts, in which a cell
      free zone between two confluent areas was allowed to populate over time and the
      migration measured. RESULTS: 24 hour incubation of prostate cell lines with
      1.15umol/l lycopene showed a 40% reduction of cellular motility in case of PC3
      cells, 58% in DU145 cells and no effect was observed for PNT2 cells. A dose
      related inhibition of cell adhesion to a basement membrane in the form of
      MatrigelTM was observed in all three cell lines and it reached statistical
      significance for PC3 and PNT2 cells at lycopene concentrations >=1.15umol/l.
      However, in case of DU145, only a concentration of 2.3umol/l showed a significant
      reduction. CONCLUSION: This in vitro investigation indicates that lycopene can
      influence the cell adhesion and migration properties of cancer cells at a dose
      which is arguably achievable in patients. The results of our study expand our
      understanding of a chemo preventive role of lycopene in prostate cancer.

PMID- 25076849
TI  - Potential dual immunomodulatory role of VEGF in ulcerative colitis and colorectal
      carcinoma.
AB  - OBJECTIVE: Progression from ulcerative colitis (UC) toward colorectal carcinoma
      (CRC) is multistep process that includes gene alterations of tumor suppressor
      genes, such as p53 and p16. The aim of this study was to investigate the
      expression patterns of p16, p53 and VEGF in affected tissue and serum levels of
      cytokines TNF-alpha, IFN-gamma, IL-4, IL-6, IL-10 and IL-17 in patients with UC
      and CRC, respectively. MATHERIALS AND METHODS. Serum levels of cytokine in
      patients with UC (n=24) and CRC (n=75) and in a healthy group (n=37) were
      analyzed by ELISA. Endoscopic biopsies specimens of UC and CRC were studied by
      immunohistochemical staining for p16, p53 and VEGF. RESULTS: Patients with UC
      with presence of extraintestinal manifestations, complications, and positive
      staining of p16, p53 and VEGF respectively had higher serum levels of pro
      inflammatory cytokines. Higher percentage of CRC patients had positive staining
      of p16, p53 and VEGF. CRC patients with positive staining of VEGF had decreased
      systemic values of pro-inflammatory IFN-gamma and increased values of
      immunosuppressive IL-10. CONCLUSIONS: Relatively low IL-10 in patients with
      severe UC is insufficient to compensate IL-6 secretion and subsequently enhanced
      type 1/17 immune response. In UC patients, p16 and p53 induce enhanced VEGF
      expression and subsequent production of pro-inflammatory TNF-alpha and IL-6. In
      CRC patients VEGF seems to have immunosuppressive role. It appears that tumor
      suppressor gene-VEGF axis have dual role on immune response in inflammation of UC
      and tumor growth and progression of CRC.

PMID- 25076851
TI  - DHRSX, a novel non-classical secretory protein associated with starvation induced
      autophagy.
AB  - Dehydrogenase/reductase (SDR family) X-linked (DHRSX) is a novel human gene
      without any substantial functional annotation and was initially cloned and
      identified in our laboratory. In this study, we present evidence that it encodes
      a non-classical secretory protein and promotes starvation induced autophagy.
      Using the Baf.A1 assay and N-terminal sequencing, we showed that DHRSX is
      secreted in a non-classical form. We expressed and purified a recombinant human
      GST-DHRSX fusion protein. Functional studies revealed that HeLa and U2OS cells
      overexpressing DHRSX or treated with the GST-DHRSX fusion protein exhibited
      higher levels of starvation-induced autophagy, resulting in increased endogenous
      LC3-II levels, a punctate GFP-LC3 distribution, and structures associated with
      autophagy, with a lower accumulation of autophagy substrates such as p62 and
      polyQ80. Accordingly, knockdown of endogenous DHRSX through specific siRNAs
      reduced LC3-II levels obviously in U2OS cells induced by starvation.
      Collectively, these results demonstrate that DHRSX is a novel non-classical
      secretory protein involved in the positive regulation of starvation induced
      autophagy and provide a new avenue for research on this protein family and
      autophagy regulation. 

PMID- 25076852
TI  - Wnt signaling as a possible promoting factor of cell differentiation in
      pleomorphic adenomas.
AB  - There are well known that Wnt signaling was some roles of cell differentiation at
      the development tissues, especially the oral and maxillofacial regions of some
      developmental stages. Therefore, to determine Wnt signaling in the pleomorphic
      adenoma tissues, we examined. The expression of Wnt1 and beta-catenin as well as
      the distribution of various cytoskeletal proteins CK7 and CK13 was examined in 30
      cases of pleomorphic adenoma by immunohistochemistry. Wnt1 was detected in almost
      all tumor cells. The peripheral columnar cells in squamous metaplasia and small
      cuboidal cells in duct-like structures were strongly positive to Wnt1. Although
      beta-catenin was clearly localized on the cell membrane of tumor cells, nuclear
      translocation was observed in small cuboidal cells and in some basaloid cells.
      The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13
      was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in
      tumor cell differentiation of peripheral columnar cells forming solid nests and
      small peripheral columnar cells forming duct-like structures. Moreover, among the
      three currently known Wnt pathways, beta-catenin is the suggested pathway working
      during cell differentiation. Furthermore, peripheral columnar cells in solid
      tumor nests and in squamous metaplasia are governed by another Wnt pathway other
      than beta-catenin. Therefore, Wnt signaling through beta-catenin pathway may be
      involved in the 'mixed' differentiation characteristic of pleomorphic adenoma
      although another pathway may also be possibly working in other parts of the tumor
      tissue. 

PMID- 25076853
TI  - Direct evidence for calcineurin binding to the exon-7 loop of the sodium
      bicarbonate cotransporter NBCn1.
AB  - The NaHCO3 cotransporter NBCn1 plays a role in neutralizing intracellular acid
      loads at the basolateral membrane in cells of the medullary thick ascending limb
      (mTAL). Calcineurin inhibitors (Cn-Is) are known to both downregulate NBCn1
      expression in the distal nephron and cause renal tubular acidosis (RTA), a risk
      factor for nephrocalcinosis and nephrolithiasis. In this report, we provide a new
      perspective on concurrent studies of NBCn1 in various tissues by using cell-free
      binding assays to investigate the interaction of NBCn1 with the calcineurin (Cn)
      isoform PPP3CA. Surface plasmon resonance (SPR) analyses show that the protein
      domain Exon 7 (translated from cassette II of NBCn1) binds Cn with an equilibrium
      dissociation constant (KD) of 30 +/- 15 nm. Linked-reaction tests suggest that
      the binding involves a conformational change. Nested PCR reactions were used to
      show that NBCn1-Exon 7 splice variants with alternative N-termini regions are
      expressed in the kidney, as well as other tissues. Additionally, we discuss NBCn1
      Exon 7 implication in acid-base balance and calcium crystallization in the
      kidney. 

PMID- 25076854
TI  - A novel role of exogenous carbon monoxide on protecting cardiac function and
      improving survival against sepsis via mitochondrial energetic metabolism pathway.
AB  - Septic cardiac dysfunction is the main cause of death in septic patients. Here we
      investigate whether exogenous carbon monoxide can protect cardiac function and
      improve survival against sepsis by interfering with mitochondrial energetic
      metabolism. Male C57BL/6 mice were subjected to cecal ligation and puncture to
      induce sepsis. Exogenous carbon monoxide delivered from
      Tricarbonyldichlororuthenium (II) dimer (carbon monoxide releasing molecule II, 8
      mg/kg) was used intravenously as intervention. We found that carbon monoxide
      significantly improved cardiac function (LVEF 80.26 +/- 2.37% vs. 71.21 +/-
      1.37%, P < 0.001; LVFS 43.52 +/- 1.92% vs. 34.93 +/- 1.28%, P < 0.001) and
      increased survival rate of septic mice (63% vs. 25%, P < 0.01). This phenomenon
      might be owing to the beneficial effect of carbon monoxide on abolishing the
      elevation of cardiac enzyme activity, cytokines levels and apoptosis rate, then
      attenuating cardiac injury in septic mice. Meanwhile, carbon monoxide
      significantly reversed the loss of mitochondrial number, effectively inhibited
      cardiac mitochondrial damage in septic mice by modulating glucose uptake,
      adenosine triphosphate and lactate content. Furthermore upregulation of
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear
      respiratory factor 1 and mitochondrial transcription factor A genes in cardiac
      tissue were revealed in septic mice treated with carbon monoxide. Taken together,
      the results indicate that exogenous carbon monoxide effectively modulated
      mitochondrial energetic metabolisms by interfering with expression of peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory
      factor 1 and mitochondrial transcription factor A genes, consequently exerted an
      important improvement in sepsis-induced cardiac dysfunction.

PMID- 25076855
TI  - Swainsonine induces apoptosis through mitochondrial pathway and caspase
      activation in goat trophoblasts.
AB  - The indolizidine alkaloid swainsonine (SW) has been reported to impair placentae
      and ultimately cause abortion in pregnant goats. Up to now, however, the precise
      effects of SW on goat trophoblast cells (GTCs) are still unclear. In this study,
      the cytotoxicity effects of SW on GTCs were detected and evaluated by MTT assay,
      AO/EB double staining, DNA fragmentation assay and flow cytometry analysis.
      Results showed that SW treatment significantly suppressed GTCs viability and
      induced typical apoptotic features in a time- and concentration-dependent manner.
      SW treatment increased Bax protein levels, reduced Bcl-2 protein levels, induced
      Bax translocation to mitochondria, and triggered the release of cytochrome c from
      mitochondria into cytosol, which in turn activated caspase-9 and caspase-3, and
      cleaved PARP, resulting in GTCs apoptosis. However, caspase-8 activity and the
      level of Bid did not exhibit significant changes in the process of SW-induced
      apoptosis. In addition, TUNEL assay suggested that SW induced GTCs apoptosis but
      not other cells in goat placenta cotyledons. Taken together, these data suggest
      that SW selectively induces GTCs apoptosis via the activation of mitochondria
      mediated apoptosis pathway in goat placenta cotyledons, which might contribute to
      placentae impairment and abortion in pregnant goats fed with SW-containing
      plants. These findings may provide new insights to understand the mechanisms
      involved in SW-caused goat's abortion. 

PMID- 25076856
TI  - Up-regulated lipocalin-2 in pulmonary hypertension involving in pulmonary artery
      SMC resistance to apoptosis.
AB  - A key feature of pulmonary hypertension (PH) is the remodeling of small pulmonary
      arteries due to abnormal pulmonary artery smooth muscle cell (PASMC)
      proliferation and resistance to apoptosis. However, the cellular mechanisms
      underlying how PASMCs in the pathological condition of pulmonary hypertension
      become resistant to apoptosis remain unknown. It was recently reported that
      lipocalin 2 (Lcn2) is up-regulated in a wide array of malignant conditions, which
      facilitates tumorigenesis partly by inhibiting cell apoptosis. In this study, we
      observed that the expression levels of Lcn2 were significantly elevated in a rat
      PH model induced with monocrotaline and in patients with congenital heart disease
      associated PH (CHD-PH) when compared with respective control. Therefore, we
      hypothesize that Lcn2 could regulate human PASMC (HPASMC) apoptosis through a
      mechanism. By the detection of DNA fragmentation using the TUNEL assay, the
      detection of Annexin V/PI-positive cells using flow cytometry, and the detection
      of cleaved caspase-3 and caspase-3 activity, we observed that Lcn2 significantly
      inhibited HPASMC apoptosis induced by serum withdrawal and H2O2 treatment. We
      also observed that Lcn2 down-regulated the proapoptotic protein Bax, decreased
      the levels of cellular ROS, and up-regulated the expression of superoxide
      dismutases (SOD1 and SOD2). In conclusion, Lcn2 significantly inhibits HPASMC
      apoptosis induced by oxidative stress via decreased intracellular ROS and
      elevated SODs. Up-regulation of Lcn2 in a rat PH model and CHD-PH patients may be
      involved in the pathological process of PH. 

PMID- 25076857
TI  - SAMD9L inactivation promotes cell proliferation via facilitating G1-S transition
      in hepatitis B virus-associated hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a highly malignant cancer with poor prognosis,
      and driver genes harboring genetic lesions and/or expression dysregulation
      contribute to hepatocarcinogenesis. Sterile Alpha Motif Domain-containing 9-like
      (SAMD9L) was a novel identified mutated gene in our previous study on exome
      sequencing of hepatitis B virus (HBV)-associated HCC, but its expression and role
      in HCC remain unknown. Here, we demonstrated that SAMD9L was frequently
      inactivated by somatic mutations, and that its expression was deregulated in HCC
      patients with hepatitis B virus (HBV) infection. SAMD9L knockdown significantly
      promoted cell proliferation, colony formation of SK-hep-1, QGY-7701, BEL-7721 and
      MHCC-97H HCC cells. Furthermore, SK-hep-1 and MHCC-97H cells with stable SAMD9L
      knockdown exhibited enhanced tumorigenicity in athymic mice. Interestingly,
      SAMD9L silence facilitated G1-S transition of cell cycle progression and led to
      the elevated activity of Wnt/beta-catenin pathway. Collectively, these findings
      highlight a novel tumor-suppressive role of SAMD9L inactivation by somatic
      mutation and decreased expression in human HBV-related HCC. 

PMID- 25076858
TI  - A small molecule agonist THIQ as a novel pharmacoperone for intracellularly
      retained melanocortin-4 receptor mutants.
AB  - Although mutations in the melanocortin-4 receptor (MC4R) gene cause severe early
      onset obesity, we still do not have effective approaches to correct the defects
      of these mutations. Several antagonists have been identified as pharmacoperones
      of the MC4R whereas no agonist of the MC4R has been reported. In the present
      study, we investigated the effect of a small molecule agonist of the MC4R, THIQ,
      on the cell surface expression and signaling of ten intracellularly retained MC4R
      mutants using different cell lines. We showed that THIQ increased the cell
      surface expression of three mutants (N62S, C84R, and C271Y) and two of them (N62S
      and C84R) had increased signaling in HEK293 cells. Interestingly, THIQ increased
      the signaling of two other mutants (P78L and P260Q) without increasing their cell
      surface expression in HEK293 cells. In neuronal cells, THIQ exhibited a more
      potent effect, correcting the cell surface expression and signaling of seven
      mutants (N62S, I69R, P78L, C84R, W174C, P260Q, and C271Y). Other mutants were not
      rescued by THIQ. We also showed that THIQ did not rescue MC4R mutants defective
      in ligand binding or signaling or one intracellularly retained mutant of the
      melanocortin-3 receptor. In summary, we demonstrated that a small molecule
      agonist acted as a pharmacoperone of the MC4R rescuing the cell surface
      expression and signaling of some intracellularly retained MC4R mutants. 

PMID- 25076859
TI  - Characteristic expression of extracellular matrix in subcutaneous adipose tissue
      development and adipogenesis; comparison with visceral adipose tissue.
AB  - Adipose tissue is a connective tissue specified for energy metabolism and
      endocrines, but functional differences between subcutaneous adipose tissue (SAT)
      and visceral adipose tissue (VAT) have not been fully elucidated. To reveal the
      physiological role of SAT, we characterized in vivo tissue development and in
      vitro adipocyte differentiation. In a DNA microarray analysis of SAT and VAT in
      Wistar rats, functional annotation clusters of extracellular matrix (ECM)-related
      genes were found in SAT, and major ECM molecules expressed in adipose tissues
      were profiled. In a histological analysis and quantitative expression analysis,
      ECM expression patterns could be classified into two types: (i) a histogenesis
      correlated type such as type IV and XV collagen, and laminin subunits, (ii) a
      high-SAT expression type such as type I, III, and V collagen and minor
      characteristic collagens. Type (i) was related to basal membrane and up-regulated
      in differentiated 3T3-L1 cells and in histogenesis at depot-specific timings. In
      contrast, type (ii) was related to fibrous forming and highly expressed in 3T3-L1
      preadipocytes. Exceptionally, fibronectin was abundant in developed adipose
      tissue, although it was highly expressed in 3T3-L1 preadipocytes. The present
      study showed that adipose tissues site-specifically regulate molecular type and
      timing of ECM expression, and suggests that these characteristic ECM molecules
      provide a critical microenvironment, which may affect bioactivity of adipocyte
      itself and interacts with other tissues. It must be important to consider the
      depot-specific property for the treatment of obesity-related disorders, dermal
      dysfunction and for the tissue regeneration. 

PMID- 25076860
TI  - Establishment and characterization of a highly tumorigenic African American
      prostate cancer cell line, E006AA-hT.
AB  - Genuine racial differences in prostate cancer (PCa) biology have been considered
      among the potential reasons to explain PCa disparities. There is no animal model
      to represent all aspects of human PCa and, more specifically, to be used for PCa
      disparity research. The lack of a spontaneously transformed in vitro cell-based
      model system has been a significant impediment to investigating and understanding
      potential molecular mechanisms, and the hormonal, genetic, and epigenetic factors
      underlying the biological and clinical aggressiveness of PCa in African American
      (AA) men. In this study, we established and characterized the E006AA-hT cell line
      as a highly tumorigenic subline of the previously characterized primary AA-PCa
      cell line, E006AA. Extensive characterization of the E006AA-hT cell line was
      accomplished using cytodifferentiation and prostate-specific markers, spectral
      karyotyping, cell line authentication assays, cell proliferation and migration
      assays, and in vitro tumorigenesis assays. Spectral karyotyping of E006AA-hT
      showed a hypertriploid chromosome complement and shared cytogenetic changes
      similar to its parental cells such as diploid X, absence of Y-chromosomes,
      numerical gains in chromosomes 5,6,8,10,17,20,21, and marker chromosomes of
      unknown origin. In addition, E006AA-hT also presented numerous clonal and
      structural aberrations such as insertion, deletion, duplication, and
      translocations in chromosomes 1-5, 8, 9, 11, 13, 14, 17, and 18. The E006AA-hT
      cell line was shown to be highly tumorigenic and produced tumors at an
      accelerated growth rate in both athymic nude and triple-deficient SCID mice.
      Silencing the mutated androgen receptor (AR-599 Ser>Gly) did not affect
      proliferation (loss-of-function), but decreased migration (gain-of-function) in
      E006AA-hT and its parental cell type. These data support that AR-point mutations
      may lead simultaneously to different "loss-of-function" and "gain-of-function"
      phenotypes in PCa cells. E006AA-Par and its subline as the only available
      spontaneously transformed low- and highly-tumorigenic primary AA-PCa cell lines
      could be used for basic and translational research aimed in supporting prostate
      cancer disparity research. 

PMID- 25076861
TI  - Identification of candidate olfactory genes in Chilo suppressalis by antennal
      transcriptome analysis.
AB  - Antennal olfaction, which is extremely important for insect survival, mediates
      key behaviors such as host preference, mate choice, and oviposition site
      selection. In insects, odor detection is mediated by multiple proteins in the
      antenna, especially the odorant receptors (ORs) and ionotropic receptors (IRs),
      which ensure the specificity of the olfactory sensory neuron responses. In this
      study, we identified the olfactory gene repertoire of the rice stem borer, Chilo
      suppressalis, an economically important agricultural pest, which inflicts great
      damage to the rice yield in south and east part of Asia, especially in Southern
      China. By Illumina sequencing of male and female antennal transcriptomes, we
      identified 47 odorant receptors, 20 ionotropic receptors, 26 odorant binding
      proteins, 21 chemosensory proteins and 2 sensory neuron membrane proteins. Our
      findings make it possible for future research of the olfactory system of C.
      suppressalis at the molecular level. 

PMID- 25076863
TI  - Native Hawaiian Voices: Enhancing the Role of Cultural Values in Community Based
      Participatory Research.
AB  - Following the goals of Community Based Participatory Research (CBPR), this paper
      describes how Native Hawaiian values emerged as a methodology for the conduct of
      a study with Native Hawaiians residing in Southern California. The equitable
      placing of community values side by side with scientific values show that
      community concepts can parallel and extend CBPR premises and are more than a
      variable to be added in the analysis. The community partners, whose voices guide
      this paper, introduced the values associated with the concepts of "aloha,"
      "malama," "maihilahila," "na'auao," and "ano ano hua." These concepts were
      employed and maintained throughout the study that assessed diet, obesity, and
      psychosocial factors related to food and nutrition as a cancer prevention method.
      We describe and examine these values in light of persistent challenges in CBPR;
      ensuring that the topic is a community driven issue, fair representation and data
      dissemination. We argue that Native Hawaiian values are touchstones that
      intersect in important ways with the goals of CBPR - equality, respecting each
      other's strengths and the elimination of health disparities for future
      generations.

PMID- 25076862
TI  - Comparative proteomic analysis of somatic embryo maturation in Carica papaya L.
AB  - BACKGROUND: Somatic embryogenesis is a complex process regulated by numerous
      factors. The identification of proteins that are differentially expressed during
      plant development could result in the development of molecular markers of plant
      metabolism and provide information contributing to the monitoring and
      understanding of different biological responses. In addition, the identification
      of molecular markers could lead to the optimization of protocols allowing the use
      of biotechnology for papaya propagation and reproduction. This work aimed to
      investigate the effects of polyethylene glycol (PEG) on somatic embryo
      development and the protein expression profile during somatic embryo maturation
      in papaya (Carica papaya L.). RESULTS: The maturation treatment supplemented with
      6% PEG (PEG6) resulted in the greatest number of somatic embryos and induced
      differential protein expression compared with cultures grown under the control
      treatment. Among 135 spots selected for MS/MS analysis, 76 spots were
      successfully identified, 38 of which were common to both treatments, while 14
      spots were unique to the control treatment, and 24 spots were unique to the PEG6
      treatment. The identified proteins were assigned to seven categories or were
      unclassified. The most representative class of proteins observed in the control
      treatment was associated with the stress response (25.8%), while those under PEG6
      treatment were carbohydrate and energy metabolism (18.4%) and the stress response
      (18.4%). CONCLUSIONS: The differential expression of three proteins (enolase,
      esterase and ADH3) induced by PEG6 treatment could play an important role in
      maturation, and these proteins could be characterized as candidate biomarkers of
      somatic embryogenesis in papaya.

PMID- 25076864
TI  - Design and implementation of an FPGA-based timing pulse programmer for pulsed
      electron paramagnetic resonance applications.
AB  - The design, construction and implementation of a field-programmable gate array
      (FPGA) -based pulse programmer for pulsed-electron paramagnetic resonance (EPR)
      experiments is described. The FPGA pulse programmer offers advantages in design
      flexibility and cost over previous pulse programmers, that are based on
      commercial digital delay generators, logic pattern generators, and application
      specific integrated circuit (ASIC) designs. The FPGA pulse progammer features a
      novel transition-based algorithm and command protocol, that is optimized for the
      timing structure required for most pulsed magnetic resonance experiments. The
      algorithm was implemented by using a Spartan-6 FPGA (Xilinx), which provides an
      easily accessible and cost effective solution for FPGA interfacing. An auxiliary
      board was designed for the FPGA-instrument interface, which buffers the FPGA
      outputs for increased power consumption and capacitive load requirements. Device
      specifications include: Nanosecond pulse formation (transition edge rise/fall
      times, <=3 ns), low jitter (<=150 ps), large number of channels (16 implemented;
      48 available), and long pulse duration (no limit). The hardware and software for
      the device were designed for facile reconfiguration to match user experimental
      requirements and constraints. Operation of the device is demonstrated and
      benchmarked by applications to 1-D electron spin echo envelope modulation (ESEEM)
      and 2-D hyperfine sublevel correlation (HYSCORE) experiments. The FPGA approach
      is transferrable to applications in nuclear magnetic resonance (NMR; magnetic
      resonance imaging, MRI), and to pulse perturbation and detection bandwidths in
      spectroscopies up through the optical range.

PMID- 25076865
TI  - Unspecific abdominal symptoms and pneumobilia: a rare case of gastrointestinal
      obstruction.
AB  - The case of a 77-year-old woman with symptoms of gastric outlet obstruction is
      presented. Transabdominal ultrasonography findings were suspicious of Bouveret's
      syndrome. Upper endoscopy confirmed this diagnosis. Bouveret's syndrome is a rare
      complication of gallstone disease caused by a bilioenteric fistula leading to
      gastric outlet obstruction by a gallstone and should be suspected in any patient
      who presents with pneumobilia without recent endoscopic retrograde
      cholangiopancreatography or biliary surgery. 

PMID- 25076866
TI  - Duodenal Hemorrhage from Pancreatic Cancer Infiltration Controlled through
      Combination Therapy with Gemcitabine and S-1.
AB  - 2.6% of pancreatic cancer patients have the primary manifestation of
      gastrointestinal bleeding. It is not feasible to stop the duodenal hemorrhage
      caused by the pancreatic cancer infiltration. A 43-year-old woman who was
      diagnosed as having pancreatic cancer with multiple hepatic metastases and
      duodenal infiltration was administered gemcitabine and S-1 combination therapy.
      During the chemotherapy, initially, bleeding occurred due to duodenal
      infiltration. However, we continued the chemotherapy and duodenal infiltration
      was markedly reduced in size and did not rebleed. Aggressive chemotherapy
      contributed to maintenance of performance status as well as improvement of
      quality of life for the patient. 

PMID- 25076867
TI  - Rapidly growing esophageal carcinosarcoma reduced by neoadjuvant radiotherapy
      alone.
AB  - Esophageal carcinosarcoma is a rare malignant neoplasm consisting of both
      carcinomatous and sarcomatous components. It is generally treated by surgery,
      radiotherapy and chemotherapy according to the protocols used for other
      esophageal cancers. However, the treatment of esophageal carcinosarcoma by
      radiotherapy alone before surgery has not been previously described. We report a
      patient with a rapidly growing esophageal carcinosarcoma that was efficiently
      reduced by neoadjuvant radiotherapy alone. A previously healthy 69-year-old man
      was admitted with dysphagia. Initial esophagogastroduodenoscopy (EGD) revealed a
      small nodular polypoid lesion of about 10 mm in the middle esophagus. A second
      EGD 1 month later showed that the tumor had expanded into a huge mass. A biopsy
      specimen revealed that the tumor comprised squamous cell carcinoma with spindle
      cell components, and the tumor was diagnosed as carcinosarcoma which was
      diagnosed as stage I (T1bN0M0). Due to renal dysfunction, the patient was treated
      with neoadjuvant radiotherapy (40 Gy) without chemotherapy. A third EGD 1 month
      later revealed remarkable tumor reduction. He then underwent total esophagectomy
      with regional lymph node dissection (pStage 0, pT1aN0M0). After surgical
      operation, the patient was followed up without adjuvant therapy. Whole body
      computed tomography revealed lung metastasis 14 months after surgery, and the
      patient died 2 months later. The neoadjuvant radiotherapy for esophageal
      carcinosarcoma was considered to have contributed to the subsequent surgery and
      his prolonged survival time. Thus, radiotherapy alone might be a suitable
      neoadjuvant therapy for esophageal carcinosarcomas. 

PMID- 25076868
TI  - An empirical comparison of different approaches for combining multimodal
      neuroimaging data with support vector machine.
AB  - In the pursuit of clinical utility, neuroimaging researchers of psychiatric and
      neurological illness are increasingly using analyses, such as support vector
      machine, that allow inference at the single-subject level. Recent studies
      employing single-modality data, however, suggest that classification accuracies
      must be improved for such utility to be realized. One possible solution is to
      integrate different data types to provide a single combined output
      classification; either by generating a single decision function based on an
      integrated kernel matrix, or, by creating an ensemble of multiple single modality
      classifiers and integrating their predictions. Here, we describe four integrative
      approaches: (1) an un-weighted sum of kernels, (2) multi-kernel learning, (3)
      prediction averaging, and (4) majority voting, and compare their ability to
      enhance classification accuracy relative to the best single-modality
      classification accuracy. We achieve this by integrating structural, functional,
      and diffusion tensor magnetic resonance imaging data, in order to compare ultra
      high risk (n = 19), first episode psychosis (n = 19) and healthy control subjects
      (n = 23). Our results show that (i) whilst integration can enhance classification
      accuracy by up to 13%, the frequency of such instances may be limited, (ii) where
      classification can be enhanced, simple methods may yield greater increases
      relative to more computationally complex alternatives, and, (iii) the potential
      for classification enhancement is highly influenced by the specific diagnostic
      comparison under consideration. In conclusion, our findings suggest that for
      moderately sized clinical neuroimaging datasets, combining different imaging
      modalities in a data-driven manner is no "magic bullet" for increasing
      classification accuracy. However, it remains possible that this conclusion is
      dependent on the use of neuroimaging modalities that had little, or no,
      complementary information to offer one another, and that the integration of more
      diverse types of data would have produced greater classification enhancement. We
      suggest that future studies ideally examine a greater variety of data types
      (e.g., genetic, cognitive, and neuroimaging) in order to identify the data types
      and combinations optimally suited to the classification of early stage psychosis.

PMID- 25076870
TI  - State-dependent value representation: evidence from the striatum.

PMID- 25076869
TI  - Intact brain processing of musical emotions in autism spectrum disorder, but more
      cognitive load and arousal in happy vs. sad music.
AB  - Music is a potent source for eliciting emotions, but not everybody experience
      emotions in the same way. Individuals with autism spectrum disorder (ASD) show
      difficulties with social and emotional cognition. Impairments in emotion
      recognition are widely studied in ASD, and have been associated with atypical
      brain activation in response to emotional expressions in faces and speech.
      Whether these impairments and atypical brain responses generalize to other
      domains, such as emotional processing of music, is less clear. Using functional
      magnetic resonance imaging, we investigated neural correlates of emotion
      recognition in music in high-functioning adults with ASD and neurotypical adults.
      Both groups engaged similar neural networks during processing of emotional music,
      and individuals with ASD rated emotional music comparable to the group of
      neurotypical individuals. However, in the ASD group, increased activity in
      response to happy compared to sad music was observed in dorsolateral prefrontal
      regions and in the rolandic operculum/insula, and we propose that this reflects
      increased cognitive processing and physiological arousal in response to emotional
      musical stimuli in this group. 

PMID- 25076871
TI  - Not all that glittered is gold: neural mechanisms that determine when reward will
      enhance or impair memory.

PMID- 25076872
TI  - Physiological and pathological phosphorylation of tau by Cdk5.
AB  - Hyperphosphorylation of microtubule-associated protein tau is one of the major
      pathological events in Alzheimer's disease (AD) and other related
      neurodegenerative diseases, including frontotemporal dementia with parkinsonism
      linked to chromosome 17 (FTDP-17). Mutations in the tau gene MAPT are a cause of
      FTDP-17, and the mutated tau proteins are hyperphosphorylated in patient brains.
      Thus, it is important to determine the molecular mechanism of
      hyperphosphorylation of tau to understand the pathology of these diseases
      collectively called tauopathy. Tau is phosphorylated at many sites via several
      protein kinases, and a characteristic is phosphorylation at Ser/Thr residues in
      Ser/Thr-Pro sequences, which are targeted by proline-directed protein kinases
      such as ERK, GSK3beta, and Cdk5. Among these kinases, Cdk5 is particularly
      interesting because it could be abnormally activated in AD. Cdk5 is a member of
      the cyclin-dependent kinases (Cdks), but in contrast to the major Cdks, which
      promote cell cycle progression in proliferating cells, Cdk5 is activated in post
      mitotic neurons via the neuron-specific activator p35. Cdk5-p35 plays a critical
      role in brain development and physiological synaptic activity. In contrast, in
      disease brains, Cdk5 is thought to be hyperactivated by p25, which is the N
      terminal truncated form of p35 and is generated by cleavage with calpain. Several
      reports have indicated that tau is hyperphosphorylated by Cdk5-p25. However,
      normal and abnormal phosphorylation of tau by Cdk5 is still not completely
      understood. In this article, we summarize the physiological and pathological
      phosphorylation of tau via Cdk5. 

PMID- 25076873
TI  - Microglia from neurogenic and non-neurogenic regions display differential
      proliferative potential and neuroblast support.
AB  - Microglia isolated from the neurogenic subependymal zone (SEZ) and hippocampus
      (HC) are capable of massive in vitro population expansion that is not possible
      with microglia isolated from non-neurogenic regions. We asked if this regional
      heterogeneity in microglial proliferative capacity is cell intrinsic, or is
      conferred by interaction with respective neurogenic or non-neurogenic niches. By
      combining SEZ and cerebral cortex (CTX) primary tissue dissociates to generate
      heterospatial cultures, we find that exposure to the SEZ environment does not
      enhance CTX microglia expansion; however, the CTX environment exerts a
      suppressive effect on SEZ microglia expansion. Furthermore, addition of purified
      donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the
      expansion of host microglia, while the addition of donor CTX microglia enhances
      the over-all microglia yield. These data suggest that SEZ and CTX microglia
      possess intrinsic, spatially restricted characteristics that are independent of
      their in vitro environment, and that they represent unique and functionally
      distinct populations. Finally, we determined that the repeated supplementation of
      neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels
      of inducible neurogenesis, provided that the ratio of microglia to total cells
      remains within a fairly narrow range. 

PMID- 25076875
TI  - Decoding methods for neural prostheses: where have we reached?
AB  - This article reviews advances in decoding methods for brain-machine interfaces
      (BMIs). Recent work has focused on practical considerations for future clinical
      deployment of prosthetics. This review is organized by open questions in the
      field such as what variables to decode, how to design neural tuning models, which
      neurons to select, how to design models of desired actions, how to learn decoder
      parameters during prosthetic operation, and how to adapt to changes in neural
      signals and neural tuning. The concluding discussion highlights the need to
      design and test decoders within the context of their expected use and the need to
      answer the question of how much control accuracy is good enough for a prosthetic.

PMID- 25076876
TI  - Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed
      by three types of motor behavior.
AB  - Both D1R and D2R knock out (KO) mice of the major dopamine receptors show
      significant motor impairments. However, there are some discrepant reports, which
      may be due to the differences in genetic background and experimental procedures.
      In addition, only few studies directly compared the motor performance of D1R and
      D2R KO mice. In this paper, we examined the behavioral difference among N10
      congenic D1R and D2R KO, and wild type (WT) mice. First, we examined spontaneous
      motor activity in the home cage environment for consecutive 5 days. Second, we
      examined motor performance using the rota-rod task, a standard motor task in
      rodents. Third, we examined motor ability with the Step-Wheel task in which mice
      were trained to run in a motor-driven turning wheel adjusting their steps on
      foothold pegs to drink water. The results showed clear differences among the mice
      of three genotypes in three different types of behavior. In monitoring
      spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h
      activities, respectively, than WT mice. In the rota-rod tasks, at a low speed,
      D1R KO mice showed poor performance but later improved, whereas D2R KO mice
      showed a good performance at early days without further improvement. When first
      subjected to a high speed task, the D2R KO mice showed poorer rota-rod
      performance at a low speed than the D1R KO mice. In the Step-Wheel task, across
      daily sessions, D2R KO mice increased the duration that mice run sufficiently
      close to the spout to drink water, and decreased time to touch the floor due to
      missing the peg steps and number of times the wheel was stopped, which
      performance was much better than that of D1R KO mice. These incongruent results
      between the two tasks for D1R and D2R KO mice may be due to the differences in
      the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward
      driven, respectively. The Step-Wheel system may become a useful tool for
      assessing the motor ability of WT and mutant mice. 

PMID- 25076877
TI  - Risk-assessment and risk-taking behavior predict potassium- and amphetamine
      induced dopamine response in the dorsal striatum of rats.
AB  - Certain personality types and behavioral traits display high correlations to drug
      use and an increased level of dopamine in the reward system is a common
      denominator of all drugs of abuse. Dopamine response to drugs has been suggested
      to correlate with some of these personality types and to be a key factor
      influencing the predisposition to addiction. This study investigated if
      behavioral traits can be related to potassium- and amphetamine-induced dopamine
      response in the dorsal striatum, an area hypothesized to be involved in the shift
      from drug use to addiction. The open field and multivariate concentric square
      fieldTM tests were used to assess individual behavior in male Wistar rats.
      Chronoamperometric recordings were then made to study the potassium- and
      amphetamine-induced dopamine response in vivo. A classification based on risk
      taking behavior in the open field was used for further comparisons. Risk-taking
      behavior was correlated between the behavioral tests and high risk takers
      displayed a more pronounced response to the dopamine uptake blocking effects of
      amphetamine. Behavioral parameters from both tests could also predict potassium-
      and amphetamine-induced dopamine responses showing a correlation between
      neurochemistry and behavior in risk-assessment and risk-taking parameters. In
      conclusion, the high risk-taking rats showed a more pronounced reduction of
      dopamine uptake in the dorsal striatum after amphetamine indicating that this
      area may contribute to the sensitivity of these animals to psychostimulants and
      proneness to addiction. Further, inherent dopamine activity was related to risk
      assessment behavior, which may be of importance for decision-making and
      inhibitory control, key components in addiction. 

PMID- 25076874
TI  - Treatment of amblyopia in the adult: insights from a new rodent model of visual
      perceptual learning.
AB  - Amblyopia is the most common form of impairment of visual function affecting one
      eye, with a prevalence of about 1-5% of the total world population. Amblyopia
      usually derives from conditions of early functional imbalance between the two
      eyes, owing to anisometropia, strabismus, or congenital cataract, and results in
      a pronounced reduction of visual acuity and severe deficits in contrast
      sensitivity and stereopsis. It is widely accepted that, due to a lack of
      sufficient plasticity in the adult brain, amblyopia becomes untreatable after the
      closure of the critical period in the primary visual cortex. However, recent
      results obtained both in animal models and in clinical trials have challenged
      this view, unmasking a previously unsuspected potential for promoting recovery
      even in adulthood. In this context, non invasive procedures based on visual
      perceptual learning, i.e., the improvement in visual performance on a variety of
      simple visual tasks following practice, emerge as particularly promising to
      rescue discrimination abilities in adult amblyopic subjects. This review will
      survey recent work regarding the impact of visual perceptual learning on
      amblyopia, with a special focus on a new experimental model of perceptual
      learning in the amblyopic rat. 

PMID- 25076879
TI  - Instrument specific use-dependent plasticity shapes the anatomical properties of
      the corpus callosum: a comparison between musicians and non-musicians.
AB  - Long-term musical expertise has been shown to be associated with a number of
      functional and structural brain changes, making it an attractive model for
      investigating use-dependent plasticity in humans. Physiological interhemispheric
      inhibition (IHI) as examined by transcranial magnetic stimulation has been shown
      to be correlated with anatomical properties of the corpus callosum as indexed by
      fractional anisotropy (FA). However, whether or not IHI or the relationship
      between IHI and FA in the corpus callosum can be modified by different musical
      training regimes remains largely unknown. We investigated this question in
      musicians with different requirements for bimanual finger movements (piano and
      string players) and non-expert controls. IHI values were generally higher in
      musicians, but differed significantly from non-musicians only in string players.
      IHI was correlated with FA in the posterior midbody of the corpus callosum across
      all participants. Interestingly, subsequent analyses revealed that this
      relationship may indeed be modulated by different musical training regimes.
      Crucially, while string players had greater IHI than non-musicians and showed a
      positive structure-function relationship, the amount of IHI in pianists was
      comparable to that of non-musicians and there was no significant structure
      function relationship. Our findings indicate instrument specific use-dependent
      plasticity in both functional (IHI) and structural (FA) connectivity of motor
      related brain regions in musicians. 

PMID- 25076880
TI  - How to measure metacognition.
AB  - The ability to recognize one's own successful cognitive processing, in e.g.,
      perceptual or memory tasks, is often referred to as metacognition. How should we
      quantitatively measure such ability? Here we focus on a class of measures that
      assess the correspondence between trial-by-trial accuracy and one's own
      confidence. In general, for healthy subjects endowed with metacognitive
      sensitivity, when one is confident, one is more likely to be correct. Thus, the
      degree of association between accuracy and confidence can be taken as a
      quantitative measure of metacognition. However, many studies use a statistical
      correlation coefficient (e.g., Pearson's r) or its variant to assess this degree
      of association, and such measures are susceptible to undesirable influences from
      factors such as response biases. Here we review other measures based on signal
      detection theory and receiver operating characteristics (ROC) analysis that are
      "bias free," and relate these quantities to the calibration and discrimination
      measures developed in the probability estimation literature. We go on to
      distinguish between the related concepts of metacognitive bias (a difference in
      subjective confidence despite basic task performance remaining constant),
      metacognitive sensitivity (how good one is at distinguishing between one's own
      correct and incorrect judgments) and metacognitive efficiency (a subject's level
      of metacognitive sensitivity given a certain level of task performance). Finally,
      we discuss how these three concepts pose interesting questions for the study of
      metacognition and conscious awareness. 

PMID- 25076881
TI  - Social and emotional relevance in face processing: happy faces of future
      interaction partners enhance the late positive potential.
AB  - Human face perception is modulated by both emotional valence and social
      relevance, but their interaction has rarely been examined. Event-related brain
      potentials (ERP) to happy, neutral, and angry facial expressions with different
      degrees of social relevance were recorded. To implement a social anticipation
      task, relevance was manipulated by presenting faces of two specific actors as
      future interaction partners (socially relevant), whereas two other face actors
      remained non-relevant. In a further control task all stimuli were presented
      without specific relevance instructions (passive viewing). Face stimuli of four
      actors (2 women, from the KDEF) were randomly presented for 1s to 26 participants
      (16 female). Results showed an augmented N170, early posterior negativity (EPN),
      and late positive potential (LPP) for emotional in contrast to neutral facial
      expressions. Of particular interest, face processing varied as a function of
      experimental tasks. Whereas task effects were observed for P1 and EPN regardless
      of instructed relevance, LPP amplitudes were modulated by emotional facial
      expression and relevance manipulation. The LPP was specifically enhanced for
      happy facial expressions of the anticipated future interaction partners. This
      underscores that social relevance can impact face processing already at an early
      stage of visual processing. These findings are discussed within the framework of
      motivated attention and face processing theories. 

PMID- 25076878
TI  - Optogenetic insights on the relationship between anxiety-related behaviors and
      social deficits.
AB  - Many psychiatric illnesses are characterized by deficits in the social domain.
      For example, there is a high rate of co-morbidity between autism spectrum
      disorders and anxiety disorders. However, the common neural circuit mechanisms by
      which social deficits and other psychiatric disease states, such as anxiety, are
      co-expressed remains unclear. Here, we review optogenetic investigations of
      neural circuits in animal models of anxiety-related behaviors and social
      behaviors and discuss the important role of the amygdala in mediating aspects of
      these behaviors. In particular, we focus on recent evidence that projections from
      the basolateral amygdala (BLA) to the ventral hippocampus (vHPC) modulate anxiety
      related behaviors and also alter social interaction. Understanding how this
      circuit influences both social behavior and anxiety may provide a mechanistic
      explanation for the pathogenesis of social anxiety disorder, as well as the
      prevalence of patients co-diagnosed with autism spectrum disorders and anxiety
      disorders. Furthermore, elucidating how circuits that modulate social behavior
      also mediate other complex emotional states will lead to a better understanding
      of the underlying mechanisms by which social deficits are expressed in
      psychiatric disease. 

PMID- 25076883
TI  - Sense of agency is related to gamma band coupling in an inferior parietal-preSMA
      circuitry.
AB  - In the present study we tested whether sense of agency (SoA) is reflected by
      changes in coupling between right medio-frontal/supplementary motor area (SMA)
      and inferior parietal cortex (IPC). Twelve healthy adult volunteers participated
      in the study. They performed a variation of a line-drawing task (Nielsen, 1963;
      Fourneret and Jeannerod, 1998), in which they moved a cursor on a digital tablet
      with their right hand without seeing the hand. Visual feedback displayed on a
      computer monitor was either in correspondence with or deviated from the actual
      movement. This made participants uncertain as to the agent of the movement and
      they reported SoA in approximately 50% of trials when the movement was computer
      generated. We tested whether IPC-preSMA coupling was associated with SoA, using
      dynamic causal modeling (DCM) for induced responses (Chen et al., 2008; Herz et
      al., 2012). Nine different DCMs were constructed for the early and late phases of
      the task, respectively. All models included two regions: a superior medial gyrus
      (preSMA) region and a right supramarginal gyrus (IPC) region. Bayesian models
      selection (Stephan et al., 2009) favored a model with input to IPC and modulation
      of the forward connection to SMA in the late task phase, and a model with input
      to preSMA and modulation of the backward connection was favored for the early
      task phase. The analysis shows that IPC source activity in the 50-60 Hz range
      modulated preSMA source activity in the 40-70 Hz range in the presence of SoA
      compared with no SoA in the late task phase, but the test of the early task phase
      did not reveal any differences between presence and absence of SoA. We show that
      SoA is associated with a directionally specific between frequencies coupling from
      IPC to preSMA in the higher gamma (gamma) band in the late task phase. This
      suggests that SoA is a retrospective perception, which is highly dependent on
      interpretation of the outcome of the performed action. 

PMID- 25076882
TI  - Stereological estimation of total cell numbers in the human cerebral and
      cerebellar cortex.
AB  - Our knowledge of the relationship between brain structure and cognitive function
      is still limited. Human brains and individual cortical areas vary considerably in
      size and shape. Studies of brain cell numbers have historically been based on
      biased methods, which did not always result in correct estimates and were often
      very time-consuming. Within the last 20-30 years, it has become possible to rely
      on more advanced and unbiased methods. These methods have provided us with
      information about fetal brain development, differences in cell numbers between
      men and women, the effect of age on selected brain cell populations, and disease
      related changes associated with a loss of function. In that this article concerns
      normal brain rather than brain disorders, it focuses on normal brain development
      in humans and age related changes in terms of cell numbers. For comparative
      purposes a few examples of neocortical neuron number in other mammals are also
      presented. 

PMID- 25076885
TI  - Neural correlates of verbal creativity: differences in resting-state functional
      connectivity associated with expertise in creative writing.
AB  - Neural characteristics of verbal creativity as assessed by word generation tasks
      have been recently identified, but differences in resting-state functional
      connectivity (rFC) between experts and non-experts in creative writing have not
      been reported yet. Previous electroencephalography (EEG) coherence measures
      during rest demonstrated a decreased cooperation between brain areas in
      association with creative thinking ability. Here, we used resting-state
      functional magnetic resonance imaging to compare 20 experts in creative writing
      and 23 age-matched non-experts with respect to rFC strengths within a brain
      network previously found to be associated with creative writing. Decreased rFC
      for experts was found between areas 44 of both hemispheres. Increased rFC for
      experts was observed between right hemispheric caudate and intraparietal sulcus.
      Correlation analysis of verbal creativity indices (VCIs) with rFC values in the
      expert group revealed predominantly negative associations, particularly of rFC
      between left area 44 and left temporal pole. Overall, our data support previous
      findings of reduced connectivity between interhemispheric areas and increased
      right-hemispheric connectivity during rest in highly verbally creative
      individuals. 

PMID- 25076887
TI  - Neuromodulation: present and emerging methods.
AB  - Neuromodulation has wide ranging potential applications in replacing impaired
      neural function (prosthetics), as a novel form of medical treatment (therapy),
      and as a tool for investigating neurons and neural function (research). Voltage
      and current controlled electrical neural stimulation (ENS) are methods that have
      already been widely applied in both neuroscience and clinical practice for
      neuroprosthetics. However, there are numerous alternative methods of stimulating
      or inhibiting neurons. This paper reviews the state-of-the-art in ENS as well as
      alternative neuromodulation techniques-presenting the operational concepts,
      technical implementation and limitations-in order to inform system design
      choices. 

PMID- 25076886
TI  - Changes in functional brain organization and behavioral correlations after
      rehabilitative therapy using a brain-computer interface.
AB  - This study aims to examine the changes in task-related brain activity induced by
      rehabilitative therapy using brain-computer interface (BCI) technologies and
      whether these changes are relevant to functional gains achieved through the use
      of these therapies. Stroke patients with persistent upper-extremity motor
      deficits received interventional rehabilitation therapy using a closed-loop
      neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments
      using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine
      Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before,
      during, after, and 1 month after therapy administration or at analogous intervals
      in the absence of therapy. Laterality Index (LI) values during finger tapping of
      each hand were calculated for each time point and assessed for correlation with
      behavioral outcomes. Brain activity during finger tapping of each hand shifted
      over the course of BCI therapy, but not in the absence of therapy, to greater
      involvement of the non-lesioned hemisphere (and lesser involvement of the stroke
      lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values
      during finger tapping of the impaired hand were correlated with gains in both
      objective and subjective behavioral measures. These findings suggest that the
      administration of interventional BCI therapy can induce differential changes in
      brain activity patterns between the lesioned and non-lesioned hemispheres and
      that these brain changes are associated with changes in specific motor functions.

PMID- 25076888
TI  - Successful Treatment of Eccrine Porocarcinoma Metastasized to a Cervical Lymph
      Node with CyberKnife Radiosurgery.
AB  - Eccrine porocarcinoma is a rare type of skin cancer that originates from eccrine
      sweat glands or acrosyringium and mainly occurs in the elderly. In this report,
      we describe an 85-year-old Japanese woman with eccrine porocarcinoma that
      metastasized to a cervical lymph node who was cured with CyberKnife radiosurgery.
      Because our patient had a high risk of perioperative complication, standard
      surgical therapy with a wide margin was impractical. Our present study suggests
      the novel possibility of using CyberKnife for the treatment of inoperable
      metastatic porocarcinoma. 

PMID- 25076889
TI  - Phrenic nerve paralysis as the initial presentation in pleural sarcomatoid
      mesothelioma.
AB  - A 74-year-old man was referred to our hospital because of persistent cough. A
      chest radiograph revealed an elevation of the right diaphragm. Computed
      tomography (CT) images revealed a small nodule localized on the right
      mediastinum. Five months later, the nodule had grown and was diagnosed as
      malignant pleural mesothelioma (MPM) by a CT-guided needle biopsy. The patient
      underwent combined chemotherapy, but the disease progressed rapidly and he passed
      away. On autopsy, microscopic findings and immunohistological examinations
      supported the diagnosis of sarcomatoid mesothelioma. Therefore, we diagnosed this
      rare case as localized sarcomatoid MPM showing phrenic nerve paralysis as an
      initial presentation. 

PMID- 25076890
TI  - Epidermal growth factor mutation as a diagnostic and therapeutic target in
      metastatic poorly differentiated thyroid carcinoma: a case report and review of
      the literature.
AB  - Poorly differentiated cancers are a diagnostic and therapeutic challenge in
      oncology. New therapies are needed for patients with poorly differentiated
      thyroid carcinoma (PDTC) or anaplastic thyroid cancer, as these patients often
      present with advanced disease and effective systemic treatment options are
      currently limited. Epidermal growth factor (EGFR) mutations may occur in PDTC
      more often than previously thought. However, there are fewer than 6 cases
      reported in the literature where EGFR tyrosine kinase inhibitors (TKIs) (such as
      erlotinib or gefitinib) were used to target EGFR mutations in PDTC. Here, we
      present the case of a 79-year-old male with metastatic PDTC with an EGFR mutation
      who responded to treatment with the selective EGFR TKI erlotinib, with a
      progression-free survival of more than 11 months. A lung primary rather than a
      thyroid primary was initially detected. We suggest that the EGFR status should be
      analysed at diagnosis in any patient with a poorly differentiated tumour. The
      presence of an EGFR mutation may provide an effective therapeutic pathway for
      these patients. This pathway requires further investigation and consideration in
      the future. 

PMID- 25076891
TI  - Successful chemotherapy with nab-Paclitaxel in a heavily treated non-small cell
      lung cancer patient: a case report.
AB  - Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancers.
      A 69-year-old female with postoperatively recurrent NSCLC was treated weekly with
      nanoparticle-albumin-bound paclitaxel (nab-paclitaxel) monotherapy every 4 weeks
      as a tenth line chemotherapy, and stable disease was achieved by seven cycles of
      this regimen. The patient developed grade 4 neutropenia and grade 3 leukopenia,
      but none of the other toxicities, including febrile neutropenia and peripheral
      neuropathy, were severe, and thus she was able to tolerate this salvage
      chemotherapy. To our knowledge this is the first report of the efficacy of nab
      paclitaxel monotherapy in a heavily treated NSCLC patient. 

PMID- 25076892
TI  - Acute Myelogenous Leukemia without Maturation with a Retinoic Alpha-Receptor
      Deletion: A Case Report.
AB  - Acute promyelocytic leukemia (APL) is characterized by a t(15;17) which fuses the
      17q retinoic acid alpha-receptor sequence to the 15q PML gene sequence. The
      resulting fusion product plays a role in the development and maintenance of APL,
      and is very rarely found in other acute myeloid leukemia (AML) subtypes. Rare
      complex APL genomic rearrangements have retinoic acid alpha-receptor sequence
      deletions. Here we report a retinoic acid alpha-receptor sequence deletion in a
      case of AML without differentiation. To our knowledge, this is the first example
      of a retinoic acid alpha-receptor sequence deletion in this AML subtype. 

PMID- 25076893
TI  - Splenic inflammatory pseudotumor-like follicular dendritic cell tumor.
AB  - Inflammatory pseudotumor of the spleen with expression of follicular dendritic
      cell markers is an extremely rare lesion with only a few cases reported
      previously. The present study reports on an inflammatory pseudotumor of the
      spleen 10 * 8 * 7 cm in size that was incidentally found in a 61-year-old man and
      increased gradually in size during a period of 3 months. Abdominal
      ultrasonography revealed a well-circumscribed splenic mass, and abdominal
      computed tomography confirmed the presence of a well-circumscribed isodense
      lesion in the splenic hilum with inhomogenous enhancement in the early-phase
      images and no enhancement on delayed-phase contrast-enhanced images. Magnetic
      resonance imaging of the abdomen showed a well-defined isodense tumor on T1
      weighted images with mildly increased signal intensity on T2-weighted images, and
      this is only the second study that provides MRI findings of this entity. The
      patient underwent an uncomplicated open splenectomy for definitive histologic
      diagnosis. Under microscopic examination, the lesion was an admixture of
      lymphocytes, plasma cells and spindle cells. In situ hybridization analysis for
      Epstein-Barr virus (EBV) revealed that most of the spindle cells were positive
      for EBV, and immunochemistry showed the expression of the follicular dendritic
      cell markers CD21, CD35 and CD23 within the tumor. The diagnosis of inflammatory
      pseudotumor-like follicular dendritic cell tumor was established. 

PMID- 25076894
TI  - Estrogen intake and copper depositions: implications for Alzheimer's disease?
AB  - We present a patient with chronic postmenopausal estrogen intake with presence of
      Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the
      pathophysiological mechanisms of estrogen intake and copper accumulation in
      various tissues, including the central nervous system. Sonography was compatible
      with copper accumulation in the basal ganglia, but the patient showed no clinical
      signs of Wilson's disease. Magnetic resonance imaging and positron emission
      tomography revealed a typical pattern for Alzheimer's disease. We propose
      increased copper levels as a direct effect of estrogen intake due to an augmented
      ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free
      serum copper on accompanying Alzheimer's disease, knowing that copper plays a
      crucial role in the formation of amyloid plaques and tau aggregation. This might
      offer a partial explanation for the observation that postmenopausal estrogen
      therapy is associated with a higher risk of mild cognitive impairment and
      Alzheimer's disease. 

PMID- 25076895
TI  - Spinal cord infarction and patent foramen ovale: is there a link?
AB  - Spinal cord infarction (SCI) is an uncommon but important cause of acute
      myelopathy. Nevertheless, contrary to cerebral stroke, the discussion about
      paradoxical embolism as a cause of cryptogenic SCI remains dubious. We describe
      the case of a 24-year-old woman who developed sudden-onset back pain followed by
      upper limb paralysis. T2-weighted MRI demonstrated hyperintense signal, extending
      from C5 to D1 with corresponding restricted diffusion on diffusion-weighted MRI
      and reduction of the apparent diffusion coefficient. Diagnostic workup, including
      lumbar puncture, showed no changes. Transcranial Doppler showed a right-to-left
      shunt with an uncountable number of microembolic signals after Valsalva
      maneuvers, and a patent foramen ovale (PFO) with an atrial septum aneurysm was
      identified. We discuss the paucity of evidence of right-to-left shunting in
      spinal diseases compared to cerebral events and the potential role of paradoxical
      embolism through PFO as a possible mechanism of SCI. 

PMID- 25076896
TI  - Isolated Gait Ataxia as a Sole Manifestation of Right Lateral Medullary Infarct
      following Ipsilateral Trigeminal Herpes Zoster.
AB  - BACKGROUND: Cerebral infarct related to varicella-zoster virus (VZV) has been
      reported in the literature. In addition, lateral medullary infarct (LMI) can be
      manifested rarely as isolated gait ataxia without other characteristic symptoms.
      CASE REPORT: A 70-year-old female was admitted to our hospital because of herpes
      zoster on the right trigeminal nerve distribution. On the 15th hospital day, she
      developed sudden vertigo and fine left-beating nystagmus with axial lateropulsion
      to the right side, without the other usual signs of LMI (Horner syndrome,
      dysarthria, swallowing difficulty or hemibody sensory change). Brain MRI showed a
      small infarct in the far dorsolateral portion of the right rostral medulla and
      pontomedullary junction. Cerebrospinal fluid study showed a positive VZV IgG
      antibody. CONCLUSIONS: We reported a case of isolated gait ataxia as the sole
      manifestation of right LMI following herpes zoster on the right trigeminal
      distribution. A high index of clinical suspicion for concomitant central nervous
      system complication is necessary in patients with herpes zoster, although the
      concomitant neurologic symptom may be mild or less lateralized.

PMID- 25076897
TI  - Toric topographically customized transepithelial, pulsed, very high-fluence,
      higher energy and higher riboflavin concentration collagen cross-linking in
      keratoconus.
AB  - PURPOSE: To report a novel application of toric topographically customized
      transepithelial collagen cross-linking (CXL) aiming to achieve refractive
      astigmatic changes in a keratoconic cornea. METHODS: Specially formulated
      riboflavin transepithelial administration and delivery of high-fluence UVA in a
      topographically customized pattern was applied in an eye with progressive
      keratoconus. Visual acuity, cornea clarity, keratometry, topography, and
      pachymetry with a multitude of modalities, as well as endothelial cell counts
      were evaluated for >6 months. RESULTS: Uncorrected distance visual acuity changed
      from preoperative 20/40 to 20/25 at 6 months. A mean astigmatic reduction of 0.8
      D, and significant cornea surface normalization was achieved 6 months
      postoperatively. There was some mild change in the epithelial distribution, with
      the treated area having a slight normalization in the average epithelial
      thickness. CONCLUSIONS: We introduce herein the novel application of a
      topographically customizable transepithelial CXL in progressive keratoconus in
      order to achieve an astigmatic refractive effect and ectasia stabilization. This
      novel technique offers a nonablative and nonincisional approach to treat
      irregular astigmatism in ectatic cornea with rapid visual rehabilitation.

PMID- 25076898
TI  - Congenital hypoplastic trigeminal nerve revealed by manifestation of corneal
      disorders likely caused by neural factor deficiency.
AB  - PURPOSE: To report a case of hypoplastic trigeminal nerve associated with corneal
      epithelial disorders that were successfully treated with peptides derived from
      substance P and insulin-like growth factor-1 (IGF-1). CASE REPORT: A 16-month-old
      boy was referred for treatment of a persistent corneal epithelial defect on his
      left eye. Magnetic resonance imaging revealed the apparent absence of the
      trigeminal nerve on the left side, and the patient was therefore diagnosed with
      neurotrophic keratopathy. Treatment with eye drops containing the tetrapeptides
      FGLM-NH2 and SSSR derived from the neuropeptide substance P and the growth factor
      IGF-1, respectively, resulted in resurfacing of the corneal epithelial defect.
      DISCUSSION: The trigeminal nerve anomaly of the patient likely gave rise to
      neurotrophic keratopathy as a result of a deficiency of neural factors,
      emphasizing the importance of neural regulation in corneal epithelial
      homeostasis.

PMID- 25076899
TI  - Xerophthalmia of Sjogren's Syndrome Diagnosed with Anti-Salivary Gland Protein 1
      Antibodies.
AB  - PURPOSE: The purpose of this report is to describe 2 patients with persistent
      severe dry eyes, positive Schirmer tests for Sjogren's syndrome (SS) but lacking
      antibodies to either Ro or La. These patients were diagnosed to have SS by
      detecting antibodies to salivary gland protein 1 (Sp1) and parotid secretory
      protein (PSP). This report emphasizes the existence of patients with SS who lack
      antibodies to either Ro or La and may therefore be misdiagnosed. Detection of
      novel autoantibodies, including antibodies to Sp1 and PSP, are helpful in
      identifying these patients. Initial presentation may simply be dry eyes. METHODS:
      Two patients who presented to our ophthalmology clinic are described. One of the
      patients underwent multiple procedures over a period of 10 years for severe
      xerophthalmia. The other patient had rheumatoid arthritis and xerophthalmia.
      However, in both patients, chronic xerophthalmia had been considered to be
      idiopathic because antibodies Ro and La were negative. Further serologic testing
      revealed antibodies to Sp1 and PSP. RESULTS: Two patients who lacked antibodies
      to Ro and La but not to Sp1 and PSP were diagnosed as having SS. CONCLUSION:
      Patients presenting with unexplained dry eyes may not always show the serology
      markers in the current criteria for SS, anti-Ro and anti-La. In these cases,
      investigation for novel, early antibodies to Sp1 and PSP is of importance in the
      diagnosis of SS.

PMID- 25076900
TI  - The role of D-serine as co-agonist of NMDA receptors in the nucleus accumbens:
      relevance to cocaine addiction.
AB  - Cocaine addiction is characterized by compulsive drug use despite adverse
      consequences and high rate of relapse during periods of abstinence. Increasing
      consensus suggests that addiction to drugs of abuse usurps learning and memory
      mechanisms normally related to natural rewards, ultimately producing long-lasting
      neuroadaptations in the mesocorticolimbic system. This system, formed in part by
      the ventral tegmental area and nucleus accumbens (NAc), has a central role in the
      development and expression of addictive behaviors. In addition to a broad
      spectrum of changes that affect morphology and function of NAc excitatory
      circuits in cocaine-treated animals, impaired N-methyl-D-aspartate receptor
      (NMDAR)-dependent synaptic plasticity is a typical feature. D-serine, a D-amino
      acid that has been found at high levels in mammalian brain, binds with high
      affinity the co-agonist site of NMDAR and mediates, along with glutamate, several
      important processes including synaptic plasticity. Here we review recent
      literature focusing on cocaine-induced impairment in synaptic plasticity
      mechanisms in the NAc and on the fundamental role of D-serine as co-agonist of
      NMDAR in functional and dysfunctional synaptic plasticity within this nucleus.
      The emerging picture is that reduced D-serine levels play a crucial role in
      synaptic plasticity relevant to cocaine addiction. This finding opens new
      perspectives for therapeutic approaches to treat this addictive state. 

PMID- 25076901
TI  - Effects of caprylic triglyceride on cognitive performance and cerebral glucose
      metabolism in mild Alzheimer's disease: a single-case observation.
AB  - OBJECTIVE: To examine the effect of 109 days of caprylic triglyceride (CT) in a
      70-year-old male with mild Alzheimer's disease (AD). BACKGROUND: Cerebral
      metabolism is limited to glucose under most conditions, and diminished cerebral
      glucose metabolism is a characteristic feature of AD. Another substrate available
      for cerebral metabolism is ketone bodies. Ketone bodies (KB) are normally derived
      from fat stores under conditions of low glucose availability as an alternative
      energy substrate to glucose. KB can also be produced by oral administration of
      CT. Prior studies suggest that the alternative energy source of CT may improve
      cognitive function due to mild to moderate AD, by circumventing the diminished
      glucose metabolism. METHOD: The effect of CT was analyzed in a single-case of
      mild AD with cognitive alterations in an open label study. Study outcomes
      included the Montreal cognitive assessment (MoCA), mini mental state exam (MMSE),
      and 18-fluorodeoxyglucose (18F) positron emission tomography (FDG PET) scans.
      RESULTS: After 109 days of CT, MoCA scores changed from a baseline value of 24
      28, and MMSE scores changed from 23 to 28. No changes were observed on FDG PET
      scans. CONCLUSION: The results suggest that, in a case of mild AD, CT may have
      affected cognitive function, assessed by means of MMSE and MoCA, although glucose
      uptake and metabolism remained unchanged.

PMID- 25076903
TI  - A low cortisol response to acute stress is related to worse basal memory
      performance in older people.
AB  - Age-related memory decline has been associated with a faulty regulation of the
      hypothalamus-pituitary-adrenal axis (HPA-axis). The aim of this study was to
      investigate whether the magnitude of the stress-induced cortisol increase is
      related to memory performance when memory is measured in non-stressful
      conditions. To do so, declarative and working memory performance were measured in
      31 men and 35 women between 55 and 77 years of age. On a different day, the
      magnitude of their cortisol response to acute psychosocial stress was measured.
      The relationship between the cortisol response and memory performance was U
      shaped: a low cortisol response to stress was related to poorer declarative and
      working memory performance, whereas those who did not increase their cortisol
      levels and those who had the largest cortisol increase had better declarative and
      working memory capabilities. Sex did not moderate these relationships. These
      results suggest that a low cortisol response to stress could reflect a defective
      HPA-axis response to stressors that is accompanied by poorer memory performance.
      Conversely, a high cortisol response seems to reflect a correct functioning of
      the HPA-axis and may protect against memory deficits in the later stages of human
      life. 

PMID- 25076904
TI  - Effects of soluble beta-amyloid on the release of neurotransmitters from rat
      brain synaptosomes.
AB  - Contradictory results have been reported on the interaction of beta-amyloid
      (Abeta) with cholinergic receptors. The present paper investigates the modulatory
      effect of Abeta1-40 on the neurotransmitter release evoked by nicotinic (nAChRs)
      and muscarinic (mAChRs) receptors. Abeta1-40 inhibits both nicotinic and
      muscarinic-evoked [(3)H]DA overflow from rat nerve endings. Added to perfusion
      medium, Abeta1-40 is able to enter into synaptosomes; it exerts its inhibitory
      effect at extracellular sites when release is stimulated by nAChRs and
      intracellularly when release is evoked by mAChRs. Moreover, our data show that
      Abeta1-40 acts as non competitive antagonist of heteromeric alpha4beta2* but not
      of alpha3beta4* nAChRs which modulate [(3)H]NA overflow. Positive allosteric
      modulators of nAChRs counteract its inhibitory effect. It might be that compounds
      of this type could be useful to prevent, slow down the appearance or reverse the
      cognitive decline typical of the normal processes of brain aging. 

PMID- 25076902
TI  - Metal and complementary molecular bioimaging in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the leading cause of dementia in the elderly,
      affecting over 27 million people worldwide. AD represents a complex neurological
      disorder which is best understood as the consequence of a number of
      interconnected genetic and lifestyle variables, which culminate in multiple
      changes to brain structure and function. These can be observed on a gross
      anatomical level in brain atrophy, microscopically in extracellular amyloid
      plaque and neurofibrillary tangle formation, and at a functional level as
      alterations of metabolic activity. At a molecular level, metal dyshomeostasis is
      frequently observed in AD due to anomalous binding of metals such as Iron (Fe),
      Copper (Cu), and Zinc (Zn), or impaired regulation of redox-active metals which
      can induce the formation of cytotoxic reactive oxygen species and neuronal
      damage. Metal chelators have been administered therapeutically in transgenic mice
      models for AD and in clinical human AD studies, with positive outcomes. As a
      result, neuroimaging of metals in a variety of intact brain cells and tissues is
      emerging as an important tool for increasing our understanding of the role of
      metal dysregulation in AD. Several imaging techniques have been used to study the
      cerebral metallo-architecture in biological specimens to obtain spatially
      resolved data on chemical elements present in a sample. Hyperspectral techniques,
      such as particle-induced X-ray emission (PIXE), energy dispersive X-ray
      spectroscopy (EDS), X-ray fluorescence microscopy (XFM), synchrotron X-ray
      fluorescence (SXRF), secondary ion mass spectrometry (SIMS), and laser ablation
      inductively coupled mass spectrometry (LA-ICPMS) can reveal relative intensities
      and even semi-quantitative concentrations of a large set of elements with
      differing spatial resolution and detection sensitivities. Other mass
      spectrometric and spectroscopy imaging techniques such as laser ablation
      electrospray ionization mass spectrometry (LA ESI-MS), MALDI imaging mass
      spectrometry (MALDI-IMS), and Fourier transform infrared spectroscopy (FTIR) can
      be used to correlate changes in elemental distribution with the underlying
      pathology in AD brain specimens. Taken together, these techniques provide new
      techniques to probe the pathobiology of AD and pave the way for identifying new
      therapeutic targets. The current review aims to discuss the advantages and
      challenges of using these emerging elemental and molecular imaging techniques,
      and highlight clinical achievements in AD research using bioimaging techniques. 

PMID- 25076905
TI  - Epitope Mapping of Antibodies to Alpha-Synuclein in LRRK2 Mutation Carriers,
      Idiopathic Parkinson Disease Patients, and Healthy Controls.
AB  - Alpha-synuclein (Snca) plays a major role in Parkinson disease (PD). Circulating
      anti-Snca antibodies has been described in PD patients and healthy controls, but
      they have been poorly characterized. This study was designed to assess the
      prevalence of anti-Snca reactivity in human subjects carrying the LRRK2 mutation,
      idiopathic PD (iPD) patients, and healthy controls and to map the epitopes of the
      anti-Snca antibodies. Antibodies to Snca were detected by ELISA and
      immunoblotting using purified recombinant Snca in plasma from individuals
      carrying LRRK2 mutations (104), iPD patients (59), and healthy controls (83).
      Epitopes of antibodies were mapped using recombinant protein constructs
      comprising different regions of Snca. Clear positive anti-Snca reactivity showed
      no correlation with age, sex, years of evolution, or the disability scores for PD
      patients and anti-Snca reactivity was not prevalent in human patients with other
      neurological or autoimmune diseases. Thirteen of the positive individuals were
      carriers of LRRK2 mutations either non-manifesting (8 out 49 screened) or
      manifesting (5 positive out 55), three positive (out of 59) were iPD patients,
      and five positive (out of 83) were healthy controls. Epitope mapping showed that
      antibodies against the N-terminal (a.a. 1-60) or C-terminal (a.a. 109-140)
      regions of Snca predominate in LRRK2 mutation carriers and iPD patients, being
      N122 a critical amino acid for recognition by the anti-C-terminal directed
      antibodies. Anti-Snca circulating antibodies seem to cluster within families
      carrying the LRRK2 mutation indicating possible genetic or common environmental
      factors in the generation of anti-Snca antibodies. These results suggest that
      case-controls' studies are insufficient and further studies in family cohorts of
      patients and healthy controls should be undertaken, to progress in the
      understanding of the possible relationship of anti-Snca antibodies and PD
      pathology. 

PMID- 25076906
TI  - Horse-racing effect and clinical trials in older persons.

PMID- 25076908
TI  - Neurodegenerative disorders: the Glia way forward.

PMID- 25076910
TI  - The value of translational biomarkers to phenotypic assays.
AB  - Phenotypic assays are tools essential for drug discovery. Phenotypic assays have
      different types of endpoints depending on the goals; (1) empirical endpoints for
      basic research to understand the underlying biology that will lead to
      identification of translation biomarkers, (2) empirical endpoints to identify
      undesired effects related to toxicity of drug candidates, and (3) knowledge-based
      endpoints (biomarkers) for drug discovery which ideally are translational
      biomarkers that will be used to identify new drug candidates and their
      corresponding molecular mechanisms of action. The value of phenotypic assays is
      increased through effective alignment of phenotypic assay endpoints with the
      objectives of the relevant stage in the drug discovery and development cycle. 

PMID- 25076907
TI  - Iron at the interface of immunity and infection.
AB  - Both, mammalian cells and microbes have an essential need for iron, which is
      required for many metabolic processes and for microbial pathogenicity. In
      addition, cross-regulatory interactions between iron homeostasis and immune
      function are evident. Cytokines and the acute phase protein hepcidin affect iron
      homeostasis leading to the retention of the metal within macrophages and
      hypoferremia. This is considered to result from a defense mechanism of the body
      to limit the availability of iron for extracellular pathogens while on the other
      hand the reduction of circulating iron results in the development of anemia of
      inflammation. Opposite, iron and the erythropoiesis inducing hormone
      erythropoietin affect innate immune responses by influencing interferon-gamma
      (IFN-gamma) mediated (iron) or NF-kB inducible (erythropoietin) immune effector
      pathways in macrophages. Thus, macrophages loaded with iron lose their ability to
      kill intracellular pathogens via IFN-gamma mediated effector pathways such as
      nitric oxide (NO) formation. Accordingly, macrophages invaded by the
      intracellular bacterium Salmonella enterica serovar Typhimurium increase the
      expression of the iron export protein ferroportin thereby reducing the
      availability of iron for intramacrophage bacteria while on the other side
      strengthening anti-microbial macrophage effector pathways via increased formation
      of NO or TNF-alpha. In addition, certain innate resistance genes such as natural
      resistance associated macrophage protein function (Nramp1) or lipocalin-2 exert
      part of their antimicrobial activity by controlling host and/or microbial iron
      homeostasis. Consequently, pharmacological or dietary modification of cellular
      iron trafficking enhances host resistance to intracellular pathogens but may
      increase susceptibility to microbes in the extracellular compartment and vice
      versa. Thus, the control over iron homeostasis is a central battlefield in host
      pathogen interplay influencing the course of an infectious disease in favor of
      either the mammalian host or the pathogenic invader. 

PMID- 25076909
TI  - Regulation of epigenetic traits of the glutathione S-transferase P1 gene: from
      detoxification toward cancer prevention and diagnosis.
AB  - Glutathione S-transferases (GSTs) are phase II drug detoxifying enzymes that play
      an essential role in the maintenance of cell integrity and protection against DNA
      damage by catalyzing the conjugation of glutathione to a wide variety of exo- and
      endogenous electrophilic substrates. Glutathione S-transferase P1 (GSTP1), the
      gene encoding the pi-class GST, is frequently inactivated by acquired somatic CpG
      island promoter hypermethylation in multiple cancer subtypes including prostate,
      breast, liver, and blood cancers. Epigenetically mediated GSTP1 silencing is
      associated with enhanced cancer susceptibility by decreasing its "caretaker" gene
      function, which tends to promote neoplastic transformation allowing cells to
      acquire additional alterations. Thus, this epigenetic alteration is now
      considered as a cancer biomarker but could as well play a driving role in
      multistep cancer development, especially well documented in prostate cancer
      development. The present review discusses applications of epigenetic alterations
      affecting GSTP1 in cancer medicine used alone or in combination with other
      biomarkers for cancer detection and diagnosis as well as for future targeted
      preventive and therapeutic interventions including by dietary agents. 

PMID- 25076911
TI  - Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin
      induced pulmonary barrier dysfunction.
AB  - RATIONALE: Antibiotic treatment of patients infected with G(-) or G(+) bacteria
      promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in
      their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human
      lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV
      1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether
      JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor (GHRH-R)
      signaling can potentially stimulate both cAMP-dependent barrier-protective
      pathways as well as barrier-disruptive protein kinase C pathways, we studied
      their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by
      means of siRNA-mediated protein kinase A (PKA) depletion. METHODS: Barrier
      function measurements were done in HL-MVEC monolayers using Electrical Cell
      substrate Impedance Sensing (ECIS) and VE-cadherin expression by Western
      blotting. Capillary leak was assessed by Evans Blue dye (EBD) incorporation.
      Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by
      multiplex analysis. PKA and PKC-alpha activity were assessed by Western blotting.
      RESULTS: GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction,
      at least in part by preserving VE-cadherin expression, while not affecting
      inflammation. In addition to activating PKA, GHRH agonist also increases PKC
      alpha activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases
      resistance in control siRNA-treated HL-MVEC, but does so even more in PKA
      depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced
      permeability in control siRNA-treated HL-MVEC, but fails to improve barrier
      function in PKA-depleted PLY-treated monolayers. CONCLUSIONS: GHRH signaling in
      HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction
      and concurrently induces a barrier-protective PKA-mediated and a barrier
      disruptive PKC-alpha-induced pathway in the presence of PLY, the former of which
      dominates the latter.

PMID- 25076912
TI  - The effect of trichostatin-A and tumor necrosis factor on expression of splice
      variants of the MaxiK and L-type channels in human myometrium.
AB  - The onset of human parturition is associated with up-regulation of pro
      inflammatory cytokines including tumor necrosis factor (TNF) as well as changes
      in ion flux, principally Ca(2+) and K(+), across the myometrial myocytes
      membrane. Elevation of intra-cellular Ca(2+) from the sarcoplasmic reticulum
      opens L-type Ca(2+) channels (LTCCs); in turn this increased calcium level
      activates MaxiK channels leading to relaxation. While the nature of how this
      cross-talk is governed remains unclear, our previous work demonstrated that the
      pro-inflammatory cytokine, TNF, and the histone deacetylase inhibitor,
      Trichostatin-A (TSA), exerted opposing effects on the expression of the pro
      quiescent Galphas gene in human myometrial cells. Consequently, in this study we
      demonstrate that the different channel splice variants for both MaxiK and LTCC
      are expressed in primary myometrial myocytes. MaxiK mRNA expression was sensitive
      to TSA stimulation, this causing repression of the M1, M3, and M4 splice
      variants. A small but not statistically significantly increase in MaxiK
      expression was also seen in response to TNF. In contrast to this, expression of
      LTCC splice variants was seen to be influenced by both TNF and TSA. TNF induced
      overall increase in total LTCC expression while TSA stimulated a dual effect:
      causing induction of LTCC exon 8 expression but repressing expression of other
      LTCC splice variants including that encoding exons 30, 31, 33, and 34, exons 30
      34 and exons 40-43. The significance of these observations is discussed herein. 

PMID- 25076913
TI  - Functional crosstalk between the mitochondrial PTP and KATP channels determine
      arrhythmic vulnerability to oxidative stress.
AB  - BACKGROUND: Mitochondrial permeability transition pore (mPTP) opening is a
      terminal event leading to mitochondrial dysfunction and cell death under
      conditions of oxidative stress (OS). However, mPTP blockade with cyclosporine A
      (CsA) has shown variable efficacy in limiting post-ischemic dysfunction and
      arrhythmias. We hypothesized that strong feedback between energy dissipating
      (mPTP) and cardioprotective (mKATP) channels determine vulnerability to OS.
      METHODS AND RESULTS: Guinea pig hearts (N = 61) were challenged with H2O2 (200
      MUM) to elicit mitochondrial membrane potential (DeltaPsim) depolarization. High
      resolution optical mapping was used to measure DeltaPsim or action potentials
      (AP) across the intact heart. Hearts were treated with CsA (0.1 MUM) under
      conditions that altered the activity of mKATP channels either directly or
      indirectly via its regulation by protein kinase C. mPTP blockade with CsA
      markedly blunted (P < 0.01) OS-induced DeltaPsim depolarization and delayed loss
      of LV pressure (LVP), but did not affect arrhythmia propensity. Surprisingly,
      prevention of mKATP activation with the chemical phosphatase BDM reversed the
      protective effect of CsA, paradoxically exacerbating OS-induced DeltaPsim
      depolarization and accelerating arrhythmia onset in CsA treated compared to
      untreated hearts (P < 0.05). To elucidate the putative molecular mechanisms, mPTP
      inhibition by CsA was tested during conditions of selective PKC inhibition or
      direct mKATP channel activation or blockade. Similar to BDM, the specific PKC
      inhibitor, CHE (10 MUM) did not alter OS-induced DeltaPsim depolarization
      directly. However, it completely abrogated CsA-mediated protection against OS.
      Direct pharmacological blockade of mKATP, a mitochondrial target of PKC
      signaling, equally abolished the protective effect of CsA on DeltaPsim
      depolarization, whereas channel activation with 30 MUM Diazoxide protected
      against DeltaPsim depolarization (P < 0.0001). Conditions that prevented mKATP
      activation either directly or indirectly via PKC inhibition led to accelerated
      DeltaPsim depolarization and early onset of VF in response to OS. Investigation
      of the electrophysiological substrate revealed accelerated APD shortening in
      response to OS in arrhythmia-prone hearts. CONCLUSIONS: Cardioprotection by CsA
      requires mKATP channel activation through a PKC-dependent pathway. Increasing
      mKATP activity during CsA administration is required for limiting OS-induced
      electrical dysfunction.

PMID- 25076914
TI  - Cognitive impairments in alcohol-dependent subjects.
AB  - Chronic excessive alcohol consumption induces cognitive impairments mainly
      affecting executive functions, episodic memory, and visuospatial capacities
      related to multiple brain lesions. These cognitive impairments not only determine
      everyday management of these patients, but also impact on the efficacy of
      management and may compromise the abstinence prognosis. Maintenance of lasting
      abstinence is associated with cognitive recovery in these patients, but some
      impairments may persist and interfere with the good conduct and the efficacy of
      management. It therefore appears essential to clearly define neuropsychological
      management designed to identify and evaluate the type and severity of alcohol
      related cognitive impairments. It is also essential to develop cognitive
      remediation therapy so that the patient can fully benefit from the management
      proposed in addiction medicine units. 

PMID- 25076916
TI  - Cannabis Use and Dependence among French Schizophrenic Inpatients.
AB  - BACKGROUND: To assess the prevalence of cannabis use and dependence in a
      population of schizophrenic inpatients and to compare schizophrenics with and
      without cannabis consumption. METHODS: One hundred one schizophrenic patients
      were examined during their first week of hospitalization. They answered the PANNS
      scale of schizophrenia, the CAGE and the Fagerstrom questionnaire, and the DSM-IV
      TR criteria for cannabis, alcohol, opiates, and nicotine use dependence were
      checked. We also assessed socio-demographic characteristics, the motive of
      cannabis consumption, and the number of cannabis joints and alcoholic drinks
      taken. RESULTS: The prevalence of cannabis consumption was 33.6% among
      schizophrenic inpatients. Schizophrenics consuming cannabis were younger than non
      schizophrenics (33.3 vs. 44.7 years p < 0.0001), more often male (77 vs. 54%, p =
      0.02) and had been hospitalized for the first time in psychiatry earlier (24.3
      vs. 31.3 p = 0.003). Eighty-eight percent of cannabis consumers were dependent on
      cannabis. They were more often dependent on opiates (17 vs. 0%) and alcohol (32
      vs. 7.4%, p = 0.001) and presented compulsive buying more often (48 vs. 27%, p =
      0.04). Logistic regression revealed that factors associated to cannabis
      consumption among schizophrenics were cannabis dependence, male gender,
      pathological gambling, opiate dependence, number of joints smoked each day, and
      compulsive buying. CONCLUSION: 33.6% of the schizophrenic patients hospitalized
      in psychiatry consume cannabis and most of them are dependent on cannabis and
      alcohol. Hospitalization in psychiatry may provide an opportunity to
      systematically identify a dependence disorder and to offer appropriate
      information and treatment.

PMID- 25076917
TI  - Interpreting null findings from trials of alcohol brief interventions.
AB  - The effectiveness of alcohol brief intervention (ABI) has been established by a
      succession of meta-analyses but, because the effects of ABI are small, null
      findings from randomized controlled trials are often reported and can sometimes
      lead to skepticism regarding the benefits of ABI in routine practice. This
      article first explains why null findings are likely to occur under null
      hypothesis significance testing (NHST) due to the phenomenon known as "the dance
      of the p-values." A number of misconceptions about null findings are then
      described, using as an example the way in which the results of the primary care
      arm of a recent cluster-randomized trial of ABI in England (the SIPS project)
      have been misunderstood. These misinterpretations include the fallacy of "proving
      the null hypothesis" that lack of a significant difference between the means of
      sample groups can be taken as evidence of no difference between their population
      means, and the possible effects of this and related misunderstandings of the SIPS
      findings are examined. The mistaken inference that reductions in alcohol
      consumption seen in control groups from baseline to follow-up are evidence of
      real effects of control group procedures is then discussed and other possible
      reasons for such reductions, including regression to the mean, research
      participation effects, historical trends, and assessment reactivity, are
      described. From the standpoint of scientific progress, the chief problem about
      null findings under the conventional NHST approach is that it is not possible to
      distinguish "evidence of absence" from "absence of evidence." By contrast, under
      a Bayesian approach, such a distinction is possible and it is explained how this
      approach could classify ABIs in particular settings or among particular
      populations as either truly ineffective or as of unknown effectiveness, thus
      accelerating progress in the field of ABI research. 

PMID- 25076915
TI  - Visual Network Asymmetry and Default Mode Network Function in ADHD: An fMRI
      Study.
AB  - BACKGROUND: A growing body of research has identified abnormal visual information
      processing in attention-deficit hyperactivity disorder (ADHD). In particular,
      slow processing speed and increased reliance on visuo-perceptual strategies have
      become evident. OBJECTIVE: The current study used recently developed fMRI methods
      to replicate and further examine abnormal rightward biased visual information
      processing in ADHD and to further characterize the nature of this effect; we
      tested its association with several large-scale distributed network systems.
      METHOD: We examined fMRI BOLD response during letter and location judgment tasks,
      and directly assessed visual network asymmetry and its association with large
      scale networks using both a voxelwise and an averaged signal approach. RESULTS:
      Initial within-group analyses revealed a pattern of left-lateralized visual
      cortical activity in controls but right-lateralized visual cortical activity in
      ADHD children. Direct analyses of visual network asymmetry confirmed atypical
      rightward bias in ADHD children compared to controls. This ADHD characteristic
      was atypically associated with reduced activation across several extra-visual
      networks, including the default mode network (DMN). We also found atypical
      associations between DMN activation and ADHD subjects' inattentive symptoms and
      task performance. CONCLUSION: The current study demonstrated rightward VNA in
      ADHD during a simple letter discrimination task. This result adds an important
      novel consideration to the growing literature identifying abnormal visual
      processing in ADHD. We postulate that this characteristic reflects greater
      perceptual engagement of task-extraneous content, and that it may be a basic
      feature of less efficient top-down task-directed control over visual processing.
      We additionally argue that abnormal DMN function may contribute to this
      characteristic.

PMID- 25076918
TI  - Production and perception of legato, portato, and staccato articulation in
      saxophone playing.
AB  - This paper investigates the production and perception of different articulation
      techniques on the saxophone. In a production experiment, two melodies were
      recorded that required different effectors to play the tones (tongue-only
      actions, finger-only actions, combined tongue and finger actions) at three
      different tempi. A sensor saxophone reed was developed to monitor tongue-reed
      interactions during performance. In the slow tempo condition, combined tongue
      finger actions showed improved timing, compared to the timing of the tongue
      alone. This observation supports the multiple timer hypothesis where the tongue's
      timekeeper benefits from a coupling to the timekeeper of the fingers. In the fast
      tempo condition, finger-only actions were less precise than tongue-only actions
      and timing precision of combined tongue-finger actions showed the higher timing
      variability, close to the level of finger-only actions. This suggests that the
      finger actions have a dominant influence on the overall timing of saxophone
      performance. In a listening experiment we investigated whether motor expertise in
      music performance influences the perception of articulation techniques in
      saxophone performance. Participants with different backgrounds in music making
      (saxophonists, musicians not playing the saxophone, and non-musicians) attended
      an AB-X listening test. They had to discriminate between saxophone phrases played
      with different articulation techniques (legato, portato, staccato). Participants
      across all three groups discriminated the sound of staccato articulation well
      from the sound of portato articulation and legato articulation. Errors occurred
      across all groups of listeners when legato articulation (no tonguing) and portato
      articulation (soft tonguing) had to be discriminated. Saxophonists' results were
      superior compared to the results of the other two groups, suggesting that
      expertise in saxophone playing facilitated the discrimination task. 

PMID- 25076919
TI  - Talker variability in audio-visual speech perception.
AB  - A change in talker is a change in the context for the phonetic interpretation of
      acoustic patterns of speech. Different talkers have different mappings between
      acoustic patterns and phonetic categories and listeners need to adapt to these
      differences. Despite this complexity, listeners are adept at comprehending speech
      in multiple-talker contexts, albeit at a slight but measurable performance cost
      (e.g., slower recognition). So far, this talker variability cost has been
      demonstrated only in audio-only speech. Other research in single-talker contexts
      have shown, however, that when listeners are able to see a talker's face, speech
      recognition is improved under adverse listening (e.g., noise or distortion)
      conditions that can increase uncertainty in the mapping between acoustic patterns
      and phonetic categories. Does seeing a talker's face reduce the cost of word
      recognition in multiple-talker contexts? We used a speeded word-monitoring task
      in which listeners make quick judgments about target word recognition in single-
      and multiple-talker contexts. Results show faster recognition performance in
      single-talker conditions compared to multiple-talker conditions for both audio
      only and audio-visual speech. However, recognition time in a multiple-talker
      context was slower in the audio-visual condition compared to audio-only
      condition. These results suggest that seeing a talker's face during speech
      perception may slow recognition by increasing the importance of talker
      identification, signaling to the listener a change in talker has occurred. 

PMID- 25076920
TI  - Measuring inconsistencies can lead you forward: Imageability and the x-ception
      theory.
AB  - According to the traditional view, both imageability and concreteness ratings
      reflect the way word meanings rely on information mediated by the senses. As a
      consequence, the two measures should and do correlate. The link between these two
      indexes was already hypothesized and demonstrated by Paivio et al. (1968) in a
      seminal article, where they introduced the idea of imageability ratings for the
      first time. However, in this first study, they also noted a contrasting pattern
      in the ratings for imageability and concreteness with some words that refer to
      affective attitudes or emotional states receiving high imageability but low
      concreteness ratings. Recent studies confirm this inconsistency (e.g., Altarriba
      and Bauer, 2004) leading to the claim that emotion words form a particular class
      of terms different from both concrete and abstract words. Here we use the MRC
      psycholinguistic database to show that the there are other classes of terms for
      which imageability and concreteness are uncorrelated. We show that the common
      feature of these word classes is that they directly or indirectly refer to
      proprioceptive, interoceptive, or affective states, i.e., to internal, body
      related, sensory experiences. Thus, imageability and concreteness can no longer
      be considered interchangeable constructs; rather, imageability is a different,
      and perhaps more interesting, measure: it not only reflects the ease with which
      memories of external events come to mind, as previously hypothesized, but also
      reflects the ease with which memories of internal events come to mind. 

PMID- 25076921
TI  - Emotion in languaging: languaging as affective, adaptive, and flexible behavior
      in social interaction.
AB  - This article argues for a view on languaging as inherently affective. Informed by
      recent ecological tendencies within cognitive science and distributed language
      studies a distinction between first order languaging (language as whole-body
      sense making) and second order language (language as system like constraints) is
      put forward. Contrary to common assumptions within linguistics and communication
      studies separating language-as-a-system from language use (resulting in
      separations between language vs. body-language and verbal vs. non-verbal
      communication etc.) the first/second order distinction sees language as emanating
      from behavior making it possible to view emotion and affect as integral parts
      languaging behavior. Likewise, emotion and affect are studied, not as inner
      mental states, but as processes of organism-environment interactions. Based on
      video recordings of interaction between (1) children with special needs, and (2)
      couple in therapy and the therapist patterns of reciprocal influences between
      interactants are examined. Through analyzes of affective stance and patterns of
      inter-affectivity it is exemplified how language and emotion should not be seen
      as separate phenomena combined in language use, but rather as completely
      intertwined phenomena in languaging behavior constrained by second order
      patterns. 

PMID- 25076922
TI  - Effect of attentional load on audiovisual speech perception: evidence from ERPs.
AB  - Seeing articulatory movements influences perception of auditory speech. This is
      often reflected in a shortened latency of auditory event-related potentials
      (ERPs) generated in the auditory cortex. The present study addressed whether this
      early neural correlate of audiovisual interaction is modulated by attention. We
      recorded ERPs in 15 subjects while they were presented with auditory, visual, and
      audiovisual spoken syllables. Audiovisual stimuli consisted of incongruent
      auditory and visual components known to elicit a McGurk effect, i.e., a visually
      driven alteration in the auditory speech percept. In a Dual task condition,
      participants were asked to identify spoken syllables whilst monitoring a rapid
      visual stream of pictures for targets, i.e., they had to divide their attention.
      In a Single task condition, participants identified the syllables without any
      other tasks, i.e., they were asked to ignore the pictures and focus their
      attention fully on the spoken syllables. The McGurk effect was weaker in the Dual
      task than in the Single task condition, indicating an effect of attentional load
      on audiovisual speech perception. Early auditory ERP components, N1 and P2,
      peaked earlier to audiovisual stimuli than to auditory stimuli when attention was
      fully focused on syllables, indicating neurophysiological audiovisual
      interaction. This latency decrement was reduced when attention was loaded,
      suggesting that attention influences early neural processing of audiovisual
      speech. We conclude that reduced attention weakens the interaction between vision
      and audition in speech. 

PMID- 25076923
TI  - Preschoolers are sensitive to free riding in a public goods game.
AB  - Despite the benefits of cooperation, selfish individuals often produce outcomes
      where everyone is worse off. This "tragedy of the commons" has been demonstrated
      experimentally in adults with the public goods game. Contributions to a public
      good decline over time due to free-riders who keep their endowments. Little is
      known about how children behave when confronted with this social dilemma. Forty
      eight preschoolers were tested using a novel non-verbal procedure and simplified
      choices more appropriate to their age than standard economic approaches. The rate
      of cooperation was initially very low and rose in the second round for the girls
      only. Children were affected by their previous outcome, as they free rode more
      after experiencing a lower outcome compared to the other group members. 

PMID- 25076924
TI  - The psychic envelopes in psychoanalytic theories of infancy.
AB  - This paper aims to review the topic of psychic envelopes and to sketch the main
      outlines of this concept in infancy. We first explore the origins of the concept
      in Freud's "protective shield" and then its development in adult psychoanalysis
      before going on to see how this fits in infancy with post-Bionian psychoanalysis
      and development. Four central notions guide this review: (1) Freud's "protective
      shield" describes a barrier to protect the psychic apparatus against potentially
      overflowing trauma. It is a core notion which highlights a serious clinical
      challenge for patients for whom the shield is damaged or faulty: the risk of
      confusion of borders between the internal/external world, conscious/unconscious,
      mind/body, or self-conservation/sexuality. (2) Anzieu's "Skin-Ego" is defined by
      the different senses of the body. The different layers of experienced sensation,
      of this body-ego, go on to form the psychic envelope. This theory contributes to
      our understanding of how early trauma, due to the failures of maternal care, can
      continue to have an impact in adult life. (3) Bick's "psychic skin" establishes
      the concept in relation to infancy. The mother's containing functions allow a
      first psychic skin to develop, which then defines an infant's psychic space and
      affords the infant a degree of self-containment. Houzel then conceptualized this
      process as a stabilization of drive forces. (4) Stern's "narrative envelope"
      derives from the intersection between psychoanalysis and neuroscience. It gives
      us another way to conceptualize the development of pre-verbal communication. It
      may also pave the way for a finer distinction of different types of envelopes.
      Ultimately, in this review we find that psychic envelopes in infancy can be
      viewed from four different perspectives (economic, topographical, dynamic, and
      genetic) and recommend further investigation. 

PMID- 25076925
TI  - Understanding expertise and non-analytic cognition in fingerprint discriminations
      made by humans.

PMID- 25076926
TI  - Analysis of minimal complex systems and complex problem solving require different
      forms of causal cognition.

PMID- 25076927
TI  - Universality of aging: family caregivers for elderly cancer patients.
AB  - The world population is aging, with the proportion of older people (65+ years)
      expected to reach 21% in 2050 and to exceed the number of younger people (aged 15
      or less) for the first time in history. Because cancer is particularly a chronic
      disease of older people, a large increase in the number of elderly patients with
      cancer is anticipated. The estimated number of new cancer cases worldwide among
      people over 65 is expected to grow from about 6 million in 2008 to more than 11
      million during the coming decade. By 2030, individuals over 65 are expected to
      account for 70% of all cancer patients in the Western world. Along with the
      increase in oncology patients, the number of older people caring for their ill
      spouses or other relatives is also growing, with the ensuing toll on these
      caregivers causing major concern, especially in western countries. In different
      societies the characteristics of family caregiver stressors, cultural norms
      concerning caregiving, and the availability of support have a huge impact on
      those providing care. Any study of older caregivers of older cancer patients
      requires an integrative evaluation of aging that takes into account cultural,
      social, psychological, and behavioral variables. This review proposes a critical
      discussion of the multidimensionality of the caregiving and of the impact that
      age, culture, and gender have on it. 

PMID- 25076928
TI  - Discrimination of speech and non-speech sounds following theta-burst stimulation
      of the motor cortex.
AB  - Perceiving speech engages parts of the motor system involved in speech
      production. The role of the motor cortex in speech perception has been
      demonstrated using low-frequency repetitive transcranial magnetic stimulation
      (rTMS) to suppress motor excitability in the lip representation and disrupt
      discrimination of lip-articulated speech sounds (Mottonen and Watkins, 2009).
      Another form of rTMS, continuous theta-burst stimulation (cTBS), can produce
      longer-lasting disruptive effects following a brief train of stimulation. We
      investigated the effects of cTBS on motor excitability and discrimination of
      speech and non-speech sounds. cTBS was applied for 40 s over either the hand or
      the lip representation of motor cortex. Motor-evoked potentials recorded from the
      lip and hand muscles in response to single pulses of TMS revealed no measurable
      change in motor excitability due to cTBS. This failure to replicate previous
      findings may reflect the unreliability of measurements of motor excitability
      related to inter-individual variability. We also measured the effects of cTBS on
      a listener's ability to discriminate: (1) lip-articulated speech sounds from
      sounds not articulated by the lips ("ba" vs. "da"); (2) two speech sounds not
      articulated by the lips ("ga" vs. "da"); and (3) non-speech sounds produced by
      the hands ("claps" vs. "clicks"). Discrimination of lip-articulated speech sounds
      was impaired between 20 and 35 min after cTBS over the lip motor representation.
      Specifically, discrimination of across-category ba-da sounds presented with an
      800-ms inter-stimulus interval was reduced to chance level performance. This
      effect was absent for speech sounds that do not require the lips for articulation
      and non-speech sounds. Stimulation over the hand motor representation did not
      affect discrimination of speech or non-speech sounds. These findings show that
      stimulation of the lip motor representation disrupts discrimination of speech
      sounds in an articulatory feature-specific way. 

PMID- 25076929
TI  - Individual differences in resting heart rate variability and cognitive control in
      posttraumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is characterized by deficits in cognitive
      functioning, particularly cognitive control. Moreover, these deficits are thought
      to play a critical role in the etiology and maintenance of core PTSD symptoms
      such as intrusive thoughts and memories. However, the psychophysiological
      concomitants of cognitive control remain largely unexamined. In this article, we
      suggest that individual differences in heart rate variability (HRV), a
      physiological index of self-regulatory capacity, may underlie the association
      between cognitive control ability and intrusive cognitions in PTSD. We review
      evidence showing that individual differences in HRV at rest are related to
      prefrontal cortical activity and performance on a broad range of cognitive
      control tasks. We highlight the importance of inhibition as a mechanism by which
      HRV promotes successful cognitive control. In addition, we summarize recent
      research linking individual differences in HRV to performance on laboratory tasks
      that assess the ability to control unwanted memories and intrusive thoughts. We
      conclude by suggesting that future studies should examine the role of low HRV as
      a risk factor for developing PTSD. 

PMID- 25076931
TI  - In praise of conscious awareness: a new framework for the investigation of
      "continuous improvement" in expert athletes.
AB  - A key postulate of traditional theories of motor skill-learning (e.g., Fitts and
      Posner, 1967; Shiffrin and Schneider, 1977) is that expert performance is largely
      automatic in nature and tends to deteriorate when the performer "reinvests" in,
      or attempts to exert conscious control over, proceduralized movements (Masters
      and Maxwell, 2008). This postulate is challenged, however, by recent empirical
      evidence (e.g., Nyberg, in press; Geeves et al., 2014) which shows that conscious
      cognitive activity plays a key role in facilitating further improvement amongst
      expert sports performers and musicians - people who have already achieved elite
      status (Toner and Moran, in press). This evidence suggests that expert performers
      in motor domains (e.g., sport, music) can strategically deploy conscious
      attention to alternate between different modes of bodily awareness (reflective
      and pre-reflective) during performance. Extrapolating from this phenomenon, the
      current paper considers how a novel theoretical approach (adapted from Sutton et
      al., 2011) could help researchers to elucidate some of the cognitive mechanisms
      mediating continuous improvement amongst expert performers. 

PMID- 25076932
TI  - Identifying differences in the experience of (in)authenticity: a latent class
      analysis approach.
AB  - Generally, psychologists consider state authenticity - that is, the subjective
      sense of being one's true self - to be a unitary and unidimensional construct,
      such that (a) the phenomenological experience of authenticity is thought to be
      similar no matter its trigger, and (b) inauthenticity is thought to be simply the
      opposing pole (on the same underlying construct) of authenticity. Using latent
      class analysis, we put this conceptualization to a test. In order to avoid over
      reliance on a Western conceptualization of authenticity, we used a cross-cultural
      sample (N = 543), comprising participants from Western, South-Asian, East-Asian,
      and South-East Asian cultures. Participants provided either a narrative in which
      the described when they felt most like being themselves or one in which they
      described when they felt least like being themselves. The analysis identified six
      distinct classes of experiences: two authenticity classes ("everyday" and
      "extraordinary"), three inauthenticity classes ("self-conscious," "deflated," and
      "extraordinary"), and a class representing convergence between authenticity and
      inauthenticity. The classes were phenomenologically distinct, especially with
      respect to negative affect, private and public self-consciousness, and self
      esteem. Furthermore, relatively more interdependent cultures were less likely to
      report experiences of extraordinary (in)authenticity than relatively more
      independent cultures. Understanding the many facets of (in)authenticity may
      enable researchers to connect different findings and explain why the attainment
      of authenticity can be difficult. 

PMID- 25076930
TI  - Broadband noise masks suppress neural responses to narrowband stimuli.
AB  - White pixel noise is widely used to estimate the level of internal noise in a
      system by injecting external variance into the detecting mechanism. Recent work
      (Baker and Meese, 2012) has provided psychophysical evidence that such noise
      masks might also cause suppression that could invalidate estimates of internal
      noise. Here we measure neural population responses directly, using steady-state
      visual evoked potentials, elicited by target stimuli embedded in different mask
      types. Sinusoidal target gratings of 1 c/deg flickered at 5 Hz, and were shown in
      isolation, or with superimposed orthogonal grating masks or 2D white noise masks,
      flickering at 7 Hz. Compared with responses to a blank screen, the Fourier
      amplitude at the target frequency increased monotonically as a function of target
      contrast when no mask was present. Both orthogonal and white noise masks caused
      rightward shifts of the contrast response function, providing evidence of
      contrast gain control suppression. We also calculated within-observer amplitude
      variance across trials. This increased in proportion to the target response,
      implying signal-dependent (i.e., multiplicative) noise at the system level, the
      implications of which we discuss for behavioral tasks. This measure of variance
      was reduced by both mask types, consistent with the changes in mean target
      response. An alternative variety of noise, which we term zero-dimensional noise,
      involves trial-by-trial jittering of the target contrast. This type of noise
      produced no gain control suppression, and increased the amplitude variance across
      trials. 

PMID- 25076933
TI  - Musical activity and emotional competence - a twin study.
AB  - The hypothesis was tested that musical activities may contribute to the
      prevention of alexithymia. We tested whether musical creative achievement and
      musical practice are associated with lower alexithymia. 8000 Swedish twins aged
      27-54 were studied. Alexithymia was assessed using the Toronto Alexithymia Scale
      20. Musical achievement was rated on a 7-graded scale. Participants estimated
      number of hours of music practice during different ages throughout life. A total
      life estimation of number of accumulated hours was made. They were also asked
      about ensemble playing. In addition, twin modelling was used to explore the
      genetic architecture of the relation between musical practice and alexithymia.
      Alexithymia was negatively associated with (i) musical creative achievement, (ii)
      having played a musical instrument as compared to never having played, and - for
      the subsample of participants that had played an instrument - (iii) total hours
      of musical training (r = -0.12 in men and -0.10 in women). Ensemble playing added
      significant variance. Twin modelling showed that alexithymia had a moderate
      heritability of 36% and that the association with musical practice could be
      explained by shared genetic influences. Associations between musical training and
      alexithymia remained significant when controlling for education, depression, and
      intelligence. Musical achievement and musical practice are associated with lower
      levels of alexithymia in both men and women. Musical engagement thus appears to
      be associated with higher emotional competence, although effect sizes are small.
      The association between musical training and alexithymia appears to be entirely
      genetically mediated, suggesting genetic pleiotropy. 

PMID- 25076935
TI  - Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement
      syndrome.
AB  - The mal de debarquement syndrome (MdDS), a continuous feeling of swaying,
      rocking, and/or bobbing, generally follows travel on the sea. The associated
      symptoms cause considerable distress. The underlying neural mechanisms are
      unknown, and to date there have been no effective treatments for this condition.
      Results in monkeys and humans suggested that MdDS was caused by maladaptation of
      the vestibulo-ocular reflex (VOR) to roll of the head during rotation. We studied
      24 subjects with persistent MdDS (3 males, 21 females; 19.1 +/- 33 months).
      Physical findings included body oscillation at 0.2 Hz, oscillating vertical
      nystagmus when the head was rolled from side-to-side in darkness, and unilateral
      rotation during the Fukuda stepping test. We posited that the maladapted rocking
      and the physical symptoms could be diminished or extinguished by readapting the
      VOR. Subjects were treated by rolling the head from side-to-side while watching a
      rotating full-field visual stimulus. Seventeen of the 24 subjects had a complete
      or substantial recovery on average for approximately 1 year. Six were initially
      better, but the symptoms recurred. One subject did not respond to treatment.
      Thus, readaptation of the VOR has led to a cure or substantial improvement in 70%
      of the subjects with MdDS. We conclude that the adaptive processes associated
      with roll-while-rotating are responsible for producing MdDS, and that the
      symptoms can be reduced or resolved by readapting the VOR. 

PMID- 25076934
TI  - Monitoring of intracranial pressure in patients with traumatic brain injury.
AB  - Since Monro published his observations on the nature of the contents of the
      intracranial space in 1783, there has been investigation of the unique
      relationship between the contents of the skull and the intracranial pressure
      (ICP). This is particularly true following traumatic brain injury (TBI), where it
      is clear that elevated ICP due to the underlying pathological processes is
      associated with a poorer clinical outcome. Consequently, there is considerable
      interest in monitoring and manipulating ICP in patients with TBI. The two
      techniques most commonly used in clinical practice to monitor ICP are via an
      intraventricular or intraparenchymal catheter with a microtransducer system. Both
      of these techniques are invasive and are thus associated with complications such
      as hemorrhage and infection. For this reason, significant research effort has
      been directed toward development of a non-invasive method to measure ICP. The
      principle aims of ICP monitoring in TBI are to allow early detection of secondary
      hemorrhage and to guide therapies that limit intracranial hypertension (ICH) and
      optimize cerebral perfusion. However, information from the ICP value and the ICP
      waveform can also be used to assess the intracranial volume-pressure
      relationship, estimate cerebrovascular pressure reactivity, and attempt to
      forecast future episodes of ICH. 

PMID- 25076936
TI  - Neurological complications in thyroid surgery: a surgical point of view on
      laryngeal nerves.
AB  - THE CERVICAL BRANCHES OF THE VAGUS NERVE THAT ARE PERTINENT TO ENDOCRINE SURGERY
      ARE THE SUPERIOR AND THE INFERIOR LARYNGEAL NERVES: their anatomical course in
      the neck places them at risk during thyroid surgery. The external branch of the
      superior laryngeal nerve (EB) is at risk during thyroid surgery because of its
      close anatomical relationship with the superior thyroid vessels and the superior
      thyroid pole region. The rate of EB injury (which leads to the paralysis of the
      cricothyroid muscle) varies from 0 to 58%. The identification of the EB during
      surgery helps avoiding both an accidental transection and an excessive
      stretching. When the nerve is not identified, the ligation of superior thyroid
      artery branches close to the thyroid gland is suggested, as well as the
      abstention from an indiscriminate use of energy-based devices that might damage
      it. The inferior laryngeal nerve (RLN) runs in the tracheoesophageal groove
      toward the larynx, close to the posterior aspect of the thyroid. It is the main
      motor nerve of the intrinsic laryngeal muscles, and also provides sensory
      innervation to the larynx. Its injury finally causes the paralysis of the
      omolateral vocal cord and various sensory alterations: the symptoms range from
      mild to severe hoarseness, to acute airway obstruction, and swallowing
      impairment. Permanent lesions of the RNL occur from 0.3 to 7% of cases, according
      to different factors. The surgeon must be aware of the possible anatomical
      variations of the nerve, which should be actively searched for and identified.
      Visual control and gentle dissection of RLN are imperative. The use of
      intraoperative nerve monitoring has been safely applied but, at the moment, its
      impact in the incidence of RLN injuries has not been clarified. In conclusion,
      despite a thorough surgical technique and the use of intraoperative
      neuromonitoring, the incidence of neurological complications after thyroid
      surgery cannot be suppressed, but should be maintained in a low range. 

PMID- 25076937
TI  - Objectively measured physical activity predicts hip and spine bone mineral
      content in children and adolescents ages 5-15 years: iowa bone development study.
AB  - This study examined the association between physical activity (PA) and bone
      mineral content (BMC; gram) from middle childhood to middle adolescence and
      compared the impact of vigorous-intensity PA (VPA) over moderate- to vigorous
      intensity PA (MVPA). Participants from the Iowa bone development study were
      examined at ages 5, 8, 11, 13, and 15 years (n = 369, 449, 452, 410, and 307,
      respectively). MVPA and VPA (minutes per day) were measured using ActiGraph
      accelerometers. Anthropometry was used to measure body size and somatic maturity.
      Spine BMC and hip BMC were measured via dual-energy x-ray absorptiometry. Sex
      specific multi-level linear models were fit for spine BMC and hip BMC, adjusted
      for weight (kilogram), height (centimeter), linear age (year), non-linear age
      (year(2)), and maturity (pre peak height velocity vs. at/post peak height
      velocity). The interaction effects of PA * maturity and PA * age were tested. We
      also examined differences in spine BMC and hip BMC between the least (10th
      percentile) and most (90th percentile) active participants at each examination
      period. Results indicated that PA added to prediction of BMC throughout the 10
      year follow-up, except MVPA, did not predict spine BMC in females. Maturity and
      age neither modify the PA effect for males nor females. At age 5, the males at
      the 90th percentile for VPA had 8.5% more hip BMC than males in the 10th
      percentile for VPA. At age 15, this difference was 2.0%. Females at age 5 in the
      90th percentile for VPA had 6.1% more hip BMC than those in the 10th percentile
      for VPA. The age 15 difference was 1.8%. VPA was associated with BMC at weight
      bearing skeletal sites from childhood to adolescence, and the effect was not
      modified by maturity or age. Our findings indicate the importance of early and
      sustained interventions that focus on VPA. Approaches focused on MVPA may be
      inadequate for optimal bone health, particularly for females. 

PMID- 25076938
TI  - Stemness is Derived from Thyroid Cancer Cells.
AB  - BACKGROUND: One hypothesis for thyroid cancer development is its derivation from
      thyroid cancer stem cells (CSCs). Such cells could arise via different paths
      including from mutated resident stem cells within the thyroid gland or via
      epithelial to mesenchymal transition (EMT) from malignant cells since EMT is
      known to confer stem-like characteristics. Furthermore, EMT is a critical process
      for epithelial tumor progression, local invasion, and metastasis formation. In
      addition, stemness provides cells with therapeutic resistance and is the likely
      cause of tumor recurrence. However, the relevance of EMT and stemness in thyroid
      cancer progression has not been extensively studied. METHODS: To examine the
      status of stemness in thyroid papillary cancer, we employed a murine model of
      thyroid papillary carcinoma and examined the expression of stemness and EMT using
      qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic
      Braf (LSL-Braf((V600E))/TPO-Cre). This construct is only activated at the time of
      thyroid peroxidase (TPO) expression in differentiating thyroid cells and cannot
      be activated by undifferentiated stem cells, which do not express TPO. RESULTS:
      There was decreased expression of thyroid-specific genes such as Tg and NIS and
      increased expression of stemness markers, such as Oct4, Rex1, CD15, and Sox2 in
      the thyroid carcinoma tissue from 6-week-old BRAF(V600E) mice indicating the
      dedifferentiated status of the cells and the fact that stemness was derived in
      this model from differentiated thyroid cells. The decreased expression of the
      epithelial marker E-cadherin and increased EMT regulators including Snail, Slug,
      and TGF-beta1 and TGF-beta3, and the mesenchymal marker vimentin demonstrated the
      simultaneous progression of EMT and the CSC-like phenotype. Stemness was also
      found in a cancer thyroid cell line (named Marca cells) derived from one of the
      murine tumors. In this cell line, we also found that overexpression of Snail
      caused up-regulation of vimentin expression and up-regulation of stemness markers
      Oct4, Rex1, and CD15, with enhanced migration ability of the cells. We also
      showed that TGF-beta1 was able to induce Snail and vimentin expression in the
      Marca cell thyroid cancer line, indicating the induction of EMT in these cells,
      and this induction of EMT and stemness was significantly inhibited by celastro a
      natural inhibitor of neoplastic cells. CONCLUSION: Our findings support our
      earlier hypothesis that stemness in thyroid cancer is derived via EMT rather than
      from resident thyroid stem cells. In mice with a thyroid-specific knock-in of
      oncogenic Braf (LSL-Braf((V600E))/TPO-Cre), the neoplastic changes were dependent
      on thyroid cell differentiation and the onset of stemness must have been derived
      from differentiated thyroid epithelial cells. Furthermore, celastrol suppressed
      TGF-beta1 induced EMT in thyroid cancer cells and may have therapeutic potential.

PMID- 25076939
TI  - Omega-3 Fatty Acids and FFAR4.
AB  - The beneficial roles of omega-3 fatty acids (omega3-FAs) on obesity, type 2
      diabetes, and other metabolic diseases are well known. Most of these effects can
      be explained by their anti-inflammatory effects triggered through their receptor,
      free fatty acid receptor 4 (FFAR4) activation. Although the whole mechanism of
      action is not fully described yet, it has been shown that stimulation of omega3
      FA to FFAR4 is followed by receptor phosphorylation. This makes FFAR4 to be
      capable of interacting with beta-arrestin-2, which in turn, results in
      association of beta-arrestin-2 with TAB1. This stealing of an important partaker
      of the inflammatory cascade leads to interruption of the pathway, resulting in
      reduced inflammation. Besides this regulation of the anti-inflammatory response,
      FFAR4 signaling also has been shown to regulate glucose homeostasis, adiposity,
      gastrointestinal peptide secretion, and taste preference. In this review, we
      summarize the current knowledge about the interaction of omega3-FAs with FFAR4
      and the consequent opportunities for the application of omega3-FAs and possible
      FFAR4 targets. 

PMID- 25076940
TI  - Increased food intake by insufficient sleep in humans: are we jumping the gun on
      the hormonal explanation?

PMID- 25076941
TI  - The ecological controls on the prevalence of candidate division TM7 in polar
      regions.
AB  - The candidate division TM7 is ubiquitous and yet uncultured phylum of the
      Bacteria that encompasses a commonly environmental associated clade, TM7-1, and a
      "host-associated" clade, TM7-3. However, as members of the TM7 phylum have not
      been cultured, little is known about what differs between these two clades. We
      hypothesized that these clades would have different environmental niches. To test
      this, we used a large-scale global soil dataset, encompassing 223 soil samples,
      their environmental parameters and associated bacterial 16S rRNA gene sequence
      data. We correlated chemical, physical and biological parameters of each soil
      with the relative abundance of the two major classes of the phylum to deduce
      factors that influence the groups' seemingly ubiquitous nature. The two classes
      of the phylum (TM7-1 and TM7-3) were indeed distinct from each other in their
      habitat requirements. A key determinant of each class' prevalence appears to be
      the pH of the soil. The class TM7-1 displays a facultative anaerobic nature with
      correlations to more acidic soils with total iron, silicon, titanium and copper
      indicating a potential for siderophore production. However, the TM7-3 class shows
      a more classical oligotrophic, heterotroph nature with a preference for more
      alkaline soils, and a probable pathogenic role with correlations to extractable
      iron, sodium and phosphate. In addition, the TM7-3 was abundant in diesel
      contaminated soils highlighting a resilient nature along with a possible carbon
      source. In addition to this both classes had unique co-occurrence relationships
      with other bacterial phyla. In particular, both groups had opposing correlations
      to the Gemmatimonadetes phylum, with the TM7-3 class seemingly being outcompeted
      by this phylum to result in a negative correlation. These ecological controls
      allow the characteristics of a TM7 phylum preferred niche to be defined and give
      insight into possible avenues for cultivation of this previously uncultured
      group. 

PMID- 25076943
TI  - Symbiont polyphyly, co-evolution, and necessity in pentatomid stinkbugs from
      Costa Rica.
AB  - Interdomain symbioses with bacteria allow insects to take advantage of
      underutilized niches and provide the foundation for their evolutionary success in
      neotropical ecosystems. The gut microbiota of 13 micro-allopatric tropical
      pentatomid species, from a Costa Rican lowland rainforest, was characterized and
      compared with insect and host plant phylogenies. Like other families within the
      Pentatomomorpha, these insects (within seven genera-Antiteuchus, Arvelius,
      Edessa, Euschistus, Loxa, Mormidea, and Sibaria) house near-monocultures of gamma
      proteobacteria in midgut crypts, comprising three distinct lineages within the
      family Enterobacteriaceae. Identity of the dominant bacteria (78-100% of the
      recovered 16S rRNA genes) was partially congruent with insect phylogeny, at the
      level of subfamily and tribe, with bacteria closely related to Erwinia observed
      in six species of the subfamily Pentatominae, and bacteria in a novel clade of
      Enterobacteriaceae for seven species within the subfamilies Edessinae and
      Discocephalinae. Symbiont replacement (i.e., bacterial "contamination" from the
      environment) may occur during maternal transmission by smearing of bacteria onto
      the egg surfaces during oviposition. This transmission strategy was
      experimentally confirmed for Sibaria englemani, and suspected for four species
      from two subfamilies, based on observation of egg probing by nymphs. Symbiont
      deprived S. englemani, acquired via egg surface sterilization, exhibited
      significantly extended second instars (9.1 days compared with 7.9 days for
      symbiotic nymphs; p = 0.0001, Wilcoxon's rank with Bonferroni correction), slower
      linearized growth rates (p = 0.005, Welch 2-sample t-test), and qualitative
      differences in ceca morphology, including increased translucency of crypts,
      elongation of extracellular cavities, and distribution of symbionts, compared to
      symbiotic nymphs. Combined, these results suggest a role of the symbiont in host
      development, the reliable transference of symbionts via egg surfaces, and a
      suggestion of co-evolution between symbiont and tropical pentatomid host insects.

PMID- 25076942
TI  - Microbial monoterpene transformations-a review.
AB  - Isoprene and monoterpenes constitute a significant fraction of new plant biomass.
      Emission rates into the atmosphere alone are estimated to be over 500 Tg per
      year. These natural hydrocarbons are mineralized annually in similar quantities.
      In the atmosphere, abiotic photochemical processes cause lifetimes of minutes to
      hours. Microorganisms encounter isoprene, monoterpenes, and other volatiles of
      plant origin while living in and on plants, in the soil and in aquatic habitats.
      Below toxic concentrations, the compounds can serve as carbon and energy source
      for aerobic and anaerobic microorganisms. Besides these catabolic reactions,
      transformations may occur as part of detoxification processes. Initial
      transformations of monoterpenes involve the introduction of functional groups,
      oxidation reactions, and molecular rearrangements catalyzed by various enzymes.
      Pseudomonas and Rhodococcus strains and members of the genera Castellaniella and
      Thauera have become model organisms for the elucidation of biochemical pathways.
      We review here the enzymes and their genes together with microorganisms known for
      a monoterpene metabolism, with a strong focus on microorganisms that are
      taxonomically validly described and currently available from culture collections.
      Metagenomes of microbiomes with a monoterpene-rich diet confirmed the ecological
      relevance of monoterpene metabolism and raised concerns on the quality of our
      insights based on the limited biochemical knowledge. 

PMID- 25076944
TI  - Physiology and molecular biology of aquatic cyanobacteria.

PMID- 25076946
TI  - Rag defects and thymic stroma: lessons from animal models.
AB  - Thymocytes and thymic epithelial cells (TECs) cross-talk is essential to support
      T cell development and preserve thymic architecture and maturation of TECs and
      Foxp3(+) natural regulatory T cells. Accordingly, disruption of thymic
      lymphostromal cross-talk may have major implications on the thymic mechanisms
      that govern T cell tolerance. Several genetic defects have been described in
      humans that affect early stages of T cell development [leading to severe combined
      immune deficiency (SCID)] or late stages in thymocyte maturation (resulting in
      combined immunodeficiency). Hypomorphic mutations in SCID-causing genes may allow
      for generation of a limited pool of T lymphocytes with a restricted repertoire.
      These conditions are often associated with infiltration of peripheral tissues by
      activated T cells and immune dysregulation, as best exemplified by Omenn syndrome
      (OS). In this review, we will discuss our recent findings on abnormalities of
      thymic microenvironment in OS with a special focus of defective maturation of
      TECs, altered distribution of thymic dendritic cells and impairment of deletional
      and non-deletional mechanisms of central tolerance. Here, taking advantage of
      mouse models of OS and atypical SCID, we will discuss how modifications in
      stromal compartment impact and shape lymphocyte differentiation, and vice versa
      how inefficient T cell signaling results in defective stromal maturation. These
      findings are instrumental to understand the extent to which novel therapeutic
      strategies should act on thymic stroma to achieve full immune reconstitution. 

PMID- 25076945
TI  - The dichotomy of pathogens and allergens in vaccination approaches.
AB  - Traditional prophylactic vaccination to prevent illness is the primary objective
      of many research activities worldwide. The golden age of vaccination began with
      an approach called variolation in ancient China and the evolution of vaccines
      still continues today with modern developments such as the production of
      Gardasil(TM) against HPV and cervical cancer. The historical aspect of how
      different forms of vaccination have changed the face of medicine and communities
      is important as it dictates our future approaches on both a local and global
      scale. From the eradication of smallpox to the use of an experimental vaccine to
      save a species, this review will explore these successes in infectious disease
      vaccination and also discuss a few significant failures which have hampered our
      efforts to eradicate certain diseases. The second part of the review will explore
      designing a prophylactic vaccine for the growing global health concern that is
      allergy. Allergies are an emerging global health burden. Of particular concern is
      the rise of food allergies in developed countries where 1 in 10 children is
      currently affected. The formation of an allergic response results from the
      recognition of a foreign component by our immune system that is usually
      encountered on a regular basis. This may be a dust-mite or a prawn but this
      inappropriate immune response can result in a life-time of food avoidance and
      lifestyle restrictions. These foreign components are very similar to antigens
      derived from infectious pathogens. The question arises: should the allergy
      community be focussing on protective measures rather than ongoing therapeutic
      interventions to deal with these chronic inflammatory conditions? We will explore
      the difficulties and benefits of prophylactic vaccination against various
      allergens by means of genetic technology that will dictate how vaccination
      against allergens could be utilized in the near future. 

PMID- 25076947
TI  - Tissue-resident T cells: dynamic players in skin immunity.
AB  - The skin is a large and complex organ that acts as a critical barrier protecting
      the body from pathogens in the environment. Numerous heterogeneous populations of
      immune cells are found within skin, including some that remain resident and
      others that can enter and exit the skin as part of their migration program.
      Pathogen-specific CD8(+) T cells that persist in the epidermis following
      infection are a unique population of memory cells with important roles in immune
      surveillance and protective responses to reinfection. How these tissue-resident
      memory T cells form in the skin, the signals controlling their persistence and
      behavior, and the mechanisms by which they mediate local recall responses are
      just beginning to be elucidated. Here, we discuss recent progress in
      understanding the roles of these skin-resident T cells and also highlight some of
      the key unanswered questions that need addressing. 

PMID- 25076950
TI  - Design Challenges for HIV-1 Vaccines Based on Humoral Immunity.

PMID- 25076949
TI  - Multiple roles of toll-like receptor 4 in colorectal cancer.
AB  - Toll-like receptor (TLR) signaling has been implicated in the inflammatory
      responses in intestinal epithelial cells (IECs). Such inflammatory signals
      mediate complex interactions between commensal bacteria and TLRs and are required
      for IEC proliferation, immune response, repair, and homeostasis. The upregulation
      of certain TLRs in colorectal cancer (CRC) tissues suggests that TLRs may play an
      essential role in the prognosis of chronic and inflammatory diseases that
      ultimately culminate in CRC. Here, we provide a comprehensive review of the
      literature on the involvement of the TLR pathway in the initiation, progression,
      and metastasis of CRC, as well as inherited genetic variation and epigenetic
      regulation. The differential expression of TLRs in epithelial cells has also been
      discussed. In particular, we emphasize the physiological role of TLR4 in CRC
      development and pathogenesis, and propose novel and promising approaches for CRC
      therapeutics with the aid of TLR ligands. 

PMID- 25076948
TI  - Organ-specific and memory treg cells: specificity, development, function, and
      maintenance.
AB  - Foxp3(+) regulatory T cells (Treg cells) are essential for establishing and
      maintaining self-tolerance, and also inhibit immune responses to innocuous
      environmental antigens. Imbalances and dysfunction in Treg cells lead to a
      variety of immune-mediated diseases, as deficits in Treg cell function contribute
      to the development autoimmune disease and pathological tissue damage, whereas
      overabundance of Treg cells can promote chronic infection and tumorigenesis.
      Recent studies have highlighted the fact that Treg cells themselves are a diverse
      collection of phenotypically and functionally specialized populations, with
      distinct developmental origins, antigen-specificities, tissue-tropisms, and
      homeostatic requirements. The signals directing the differentiation of these
      populations, their specificities and the mechanisms by which they combine to
      promote organ-specific and systemic tolerance, and how they embody the emerging
      property of regulatory memory are the focus of this review. 

PMID- 25076951
TI  - BASIC AMINO ACID CARRIER 2 gene expression modulates arginine and urea content
      and stress recovery in Arabidopsis leaves.
AB  - In plants, basic amino acids are important for the synthesis of proteins and
      signaling molecules and for nitrogen recycling. The Arabidopsis nuclear gene
      BASIC AMINO ACID CARRIER 2 (BAC2) encodes a mitochondria-located carrier that
      transports basic amino acids in vitro. We present here an analysis of the
      physiological and genetic function of BAC2 in planta. When BAC2 is overexpressed
      in vivo, it triggers catabolism of arginine, a basic amino acid, leading to
      arginine depletion and urea accumulation in leaves. BAC2 expression was known to
      be strongly induced by stress. We found that compared to wild type plants, bac2
      null mutants (bac2-1) recover poorly from hyperosmotic stress when restarting
      leaf expansion. The bac2-1 transcriptome differs from the wild-type transcriptome
      in control conditions and under hyperosmotic stress. The expression of genes
      encoding stress-related transcription factors (TF), arginine metabolism enzymes,
      and transporters is particularly disturbed in bac2-1, and in control conditions,
      the bac2-1 transcriptome has some hallmarks of a wild-type stress transcriptome.
      The BAC2 carrier is therefore involved in controlling the balance of arginine and
      arginine-derived metabolites and its associated amino acid metabolism is
      physiologically important in equipping plants to respond to and recover from
      stress. 

PMID- 25076952
TI  - Protein body formation in the endoplasmic reticulum as an evolution of storage
      protein sorting to vacuoles: insights from maize gamma-zein.
AB  - The albumin and globulin seed storage proteins present in all plants accumulate
      in storage vacuoles. Prolamins, which are the major proteins in cereal seeds and
      are present only there, instead accumulate within the endoplasmic reticulum (ER)
      lumen as very large insoluble polymers termed protein bodies. Inter-chain
      disulfide bonds play a major role in polymerization and insolubility of many
      prolamins. The N-terminal domain of the maize prolamin 27 kD gamma-zein is able
      to promote protein body formation when fused to other proteins and contains seven
      cysteine residues involved in inter-chain bonds. We show that progressive
      substitution of these amino acids with serine residues in full length gamma-zein
      leads to similarly progressive increase in solubility and availability to traffic
      from the ER along the secretory pathway. Total substitution results in very
      efficient secretion, whereas the presence of a single cysteine is sufficient to
      promote partial sorting to the vacuole via a wortmannin-sensitive pathway,
      similar to the traffic pathway of vacuolar storage proteins. We propose that the
      mechanism leading to accumulation of prolamins in the ER is a further
      evolutionary step of the one responsible for accumulation in storage vacuoles. 

PMID- 25076954
TI  - A dynamic interplay between membranes and the cytoskeleton critical for cell
      development and signaling.

PMID- 25076953
TI  - Auxin polar transport in stamen formation and development: how many actors?
AB  - In flowering plants, proper development of stamens, the male reproductive organs,
      is required for successful sexual reproduction. In Arabidopsis thaliana normally
      six stamen primordia arise in the third whorl of floral organs and subsequently
      differentiate into stamen filaments and anthers, where male meiosis occurs, thus
      ending the early developmental phase. This early phase is followed by a late
      developmental phase, which consists of a rapid elongation of stamen filaments
      coordinated with anther dehiscence and pollen maturation, and terminates with
      mature pollen grain release at anthesis. Increasing evidence suggests that auxin
      transport is necessary for both early and late phases of stamen development. It
      has been shown that different members of PIN (PIN-FORMED) family are involved in
      the early phase, whereas members of both PIN and P-glycoproteins of the ABCB
      (PGP) transporter families are required during the late developmental phase. In
      this review we provide an overview of the increasing knowledge on auxin
      transporters involved in Arabidopsis stamen formation and development and we
      discuss their role and functional conservation across plant species. 

PMID- 25076956
TI  - Evaluation of the implementation of a rapid response treatment protocol for
      patients with acute onset stroke: can we increase the number of patients treated
      and shorten the time needed?
AB  - AIMS: This study aims to evaluate the implementation of a rapid response
      treatment protocol for patients presenting with acute onset ischemic stroke.
      Improvements of routines surrounding the admission and treatment of patients with
      intravenous thrombolysis (IVT), such as door-to-needle (DTN) times, and
      increasing the numbers of patients treated are discussed. METHODS: We conducted a
      retrospective analysis of all patients (n = 320) treated with IVT for acute onset
      ischemic stroke at the Stavanger University Hospital, Norway, between 2003 and
      2012. In 2009, a succession of changes to pre- and intra-hospital routines were
      made as well as an improvement in the education of primary health care
      physicians, nurses and paramedics involved in the treatment of acute onset stroke
      patients (rapid response treatment protocol). Analyses of DTN times, onset-to
      needle times and the number of patients treated per year were carried out to
      ascertain the effect of the changes made. The primary aim was to analyze DTN
      times to look for any changes, and the secondary aim was to analyze changes in
      the number of patients treated per year. RESULTS: In the years after the
      implementation of the rapid treatment protocol, we saw an improvement in the
      median DTN time with a decrease from 73 to 50 min in the first year (p = 0.03), a
      decrease of 45 min in the second year (p = 0.01) and a decrease of 31 min in the
      third year (p < 0.001). Similarly, an improvement in the number of patients
      treated per year was seen after enhancements in the treatment chain were made. A
      significant, 27-fold increase was shown when the number of patients treated in
      2012 was compared with all patients treated in all years prior to the
      implementation of the rapid treatment protocol. CONCLUSIONS: The implementation
      of the rapid treatment protocol for acute onset ischemic stroke patients led to a
      significant decrease in the DTN time at our center. These improvements also
      produced an increase in the number of patients treated per year. The extension of
      the therapeutic window from 3 to 4.5 h for the use of intravenous recombinant
      tissue plasminogen activator also played a role in the increased treatment
      numbers.

PMID- 25076955
TI  - The mitochondrial Ras-related GTPase Miro: views from inside and outside the
      metazoan kingdom.
AB  - Miro GTPase, a member of the Ras superfamily, consists of two GTPase domains
      flanking a pair of EF hand motifs and a C-terminal transmembrane domain that
      anchors the protein to the mitochondrial outer membrane. Since the identification
      of Miro in humans, a series of studies in metazoans, including mammals and fruit
      flies, have shown that Miro plays a role in the calcium-dependent regulation of
      mitochondrial transport along microtubules. However, in non-metazoans, including
      yeasts, slime molds, and plants, Miro is primarily involved in the maintenance of
      mitochondrial morphology and homeostasis. Given the high level of conservation of
      Miro in eukaryotes and the variation in the molecular mechanisms of mitochondrial
      transport between eukaryotic lineages, Miro may have a common ancestral function
      in mitochondria, and its roles in the regulation of mitochondrial transport may
      have been acquired specifically by metazoans after the evolutionary divergence of
      eukaryotes. 

PMID- 25076957
TI  - Preoperative white matter lesions are independent predictors of long-term
      survival after internal carotid endarterectomy.
AB  - BACKGROUND: Cerebral white matter lesions (WMLs) predict long-term survival of
      conservatively treated acute stroke patients with etiology other than carotid
      stenosis. In carotid endarterectomy patients, WMLs are associated with severe
      carotid stenosis and unstable plaques, with the risk of perioperative
      complications and with increased 30-day perioperative risk of death. However, no
      data exist on their effect on postoperative long-term survival, a factor
      important when considering the net benefit from carotid endarterectomy. Whether
      this effect is independent of classical risk factors and indications for surgery
      is not known either. We hypothesized that WMLs could be evaluated from
      preoperative routine computed tomography (CT) scans and are predictors of
      postoperative survival, independent of classical cardiovascular risk factors,
      indication category and degree of carotid stenosis. METHODS: A total of 353 of
      481 (73.4%) consecutive patients subjected to carotid endarterectomy due to
      different indications, i.e. asymptomatic stenosis (n = 28, 7.9%), amaurosis fugax
      (n = 52, 14.7%), transient ischemic attack (n = 135, 38.2%) or ischemic stroke (n
      = 138, 39.1%), from prospective vascular registries during the years 2001-2010
      with digital preoperative CT scans, were included in the study. WMLs were rated
      by a radiologist (Wahlund criteria) in a blinded fashion. Internal carotid artery
      (ICA) stenoses were angiographically graded (<50, 50-69, 70-99 and 100%). Odds
      ratios (ORs) and hazard ratios (HRs) are reported (ORs and HRs <=1 indicate a
      beneficial effect). The median follow-up time was 67 months (interquartile range
      45.5, range 0-129 months). Spearman's rho was used to estimate intraobserver
      agreement. Binary logistic regression was performed to analyze the association of
      risk factors with WMLs. Cox regression proportional hazards analysis was used to
      study the effect of different factors on survival. RESULTS: WML severity could be
      assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p <
      0.0001). Only age (OR 1.10, 95% CI 1.06-1.15; p < 0.0001 per year), degree of
      ipsilateral ICA stenosis (OR 2.22, 95% CI 1.08-4.55; p < 0.05 per stenosis grade)
      and indication category (OR 1.63, 95% CI 1.19-2.24; p < 0.01 per category)
      remained independently associated with WMLs. Age (HR 1.04, 95% CI 1.01-1.08; p <
      0.05 per year), diabetes (HR 1.59, 95% CI 1.01-2.49; p < 0.05), peripheral
      arterial disease (HR 2.47, 95% CI 1.46-4.15; p < 0.01), degree of ipsilateral ICA
      stenosis (HR 2.56, 95% CI 1.12-5.87; p < 0.05 per stenosis grade) and WMLs (HR
      3.83, 95% CI 1.17-12.5; p < 0.05) remained independently associated with
      increased long-term mortality. CONCLUSIONS: WMLs in a preoperative CT scan
      provide a substantially reliable estimate of postoperative long-term survival of
      carotid endarterectomy patients independent of currently used criteria, i.e.
      cardiovascular risk factors, indication category and degree of ipsilateral ICA
      stenosis.

PMID- 25076958
TI  - Neurocognitive functioning after carotid revascularization: a systematic review.
AB  - BACKGROUND: The objective of this study was to review the recent literature
      regarding the neurocognitive consequences of carotid endarterectomy (CEA) and
      carotid stenting (CAS). METHODS AND RESULTS: A PubMed and Web of Science search
      was conducted using the key words 'carotid' in combination with 'cognitive',
      'cognition', 'neurocognition', 'neurocognitive', 'neuropsychology', and
      'neuropsychological'. Bibliographies of relevant articles were cross-referenced.
      We included 37 studies published since 2007 of which 18 examined CEA, 12 CAS, and
      7 compared CEA to CAS. There is a wide variability in the reported neurocognitive
      outcome following CEA and CAS. Nonetheless, none of the included studies unveiled
      significant differences between CEA and CAS on postoperative neurocognitive
      functioning. Postoperative changes observed for CEA and CAS separately seem
      limited to a small percentage (around 10-15%) of patients and can either present
      as an improvement or impairment. KEY MESSAGES: The available data seem to suggest
      that no obvious cognitive differences between CAS and CEA can be observed after
      intervention. Both improvement and deterioration in cognitive functioning can be
      observed following CAS or CEA. Methodological differences such as patient
      heterogeneity, implementation and type of control groups, type of psychometric
      tests used, statistical analyses, or timing of the assessments play an important
      role in explaining the sometimes divergent results of the included studies. Large
      scale and methodologically solid studies comparing CEA and CAS on neurocognitive
      outcome remain warranted. Future studies should implement adequate control groups
      to correct for practice effects in the target groups.

PMID- 25076959
TI  - Measuring Quality Improvement in Acute Ischemic Stroke Care: Interrupted Time
      Series Analysis of Door-to-Needle Time.
AB  - BACKGROUND: In patients with acute ischemic stroke, early treatment with
      recombinant tissue plasminogen activator (rtPA) improves functional outcome by
      effectively reducing disability and dependency. Timely thrombolysis, within 1 h,
      is a vital aspect of acute stroke treatment, and is reflected in the widely used
      performance indicator 'door-to-needle time' (DNT). DNT measures the time from the
      moment the patient enters the emergency department until he/she receives
      intravenous rtPA. The purpose of the study was to measure quality improvement
      from the first implementation of thrombolysis in stroke patients in a university
      hospital in the Netherlands. We further aimed to identify specific interventions
      that affect DNT. METHODS: We included all patients with acute ischemic stroke
      consecutively admitted to a large university hospital in the Netherlands between
      January 2006 and December 2012, and focused on those treated with thrombolytic
      therapy on admission. Data were collected routinely for research purposes and
      internal quality measurement (the Erasmus Stroke Study). We used a retrospective
      interrupted time series design to study the trend in DNT, analyzed by means of
      segmented regression. RESULTS: Between January 2006 and December 2012, 1,703
      patients with ischemic stroke were admitted and 262 (17%) were treated with rtPA.
      Patients treated with thrombolysis were on average 63 years old at the time of
      the stroke and 52% were male. Mean age (p = 0.58) and sex distribution (p = 0.98)
      did not change over the years. The proportion treated with thrombolysis increased
      from 5% in 2006 to 22% in 2012. In 2006, none of the patients were treated within
      1 h. In 2012, this had increased to 81%. In a logistic regression analysis, this
      trend was significant (OR 1.6 per year, CI 1.4-1.8). The median DNT was reduced
      from 75 min in 2006 to 45 min in 2012 (p < 0.001 in a linear regression model).
      In this period, a 12% annual decrease in DNT was achieved (CI from 16 to 8%). We
      could not find a significant association between any specific intervention and
      the trend in DNT. CONCLUSION AND IMPLICATIONS: The DNT steadily improved from the
      first implementation of thrombolysis. Specific explanations for this improvement
      require further study, and may relate to the combined impact of a series of
      structural and logistic interventions. Our results support the use of performance
      measures for internal communication. Median DNT should be used on a monthly or
      quarterly basis to inform all professionals treating stroke patient of their
      achievements.

PMID- 25076960
TI  - Nondialytic therapy for elderly patients in a critical care setting.
AB  - It is frequently necessary to admit critically ill elderly patients to intensive
      care units (ICUs) due to their physiological impairments and co-morbidities.
      Several life-sustaining therapies such as mechanical ventilation are performed as
      necessary treatment in these ICUs. Sometimes renal replacement therapy (i.e.
      dialysis) is considered for elderly patients with complicating serious renal
      insufficiency. However, although the necessity for dialysis is recognized, some
      elderly patients may not benefit from this care because of their limited life
      expectancy. Until recently, life-sustaining support for critically ill elderly
      patients in Japan has been used routinely, regardless of the medical futility.
      The issue of providing better end-of-life care for elderly patients even in the
      ICU is now being raised frequently. We therefore wish to highlight the issue of
      end-of-life care and decision-making in the ICU, focusing on nondialytic therapy
      (NDT). The aim of this article was to assess whether NDT is an acceptable
      optional care for critically ill elderly patients with serious kidney diseases,
      even in the ICU. We hope our experiences may be helpful to physicians with an
      interest in decision-making and end-of-life care. 

PMID- 25076961
TI  - A case of bladder-inverted papilloma after brachytherapy for prostate cancer.
AB  - An 82-year-old male who presented with the chief complaint of gross hematuria and
      a history of prostate cancer treated with brachytherapy 6 years previously is
      described. Cystoscopy revealed multiple bladder tumors on the right posterior
      wall. A transurethral resection of the bladder tumor was performed and a
      pathological diagnosis of the inverted papilloma was made. To the best of our
      knowledge, this case is the first report of bladder-inverted papilloma after
      brachytherapy for prostate cancer. 

PMID- 25076962
TI  - Normoglycemic diabetic nephropathy: the role of insulin resistance.
AB  - The pathophysiology of diabetic nephropathy (DN) is complex and incompletely
      understood. Whereas hyperglycemia is clearly important, the role of insulin
      resistance (IR) is increasingly recognized. We present the case of a normotensive
      non-smoking obese woman with nephrotic syndrome who was found to have DN by
      biopsy. All measures of glucose metabolism, including fasting glucose,
      glycosylated hemoglobin, and oral glucose tolerance testing, were repeatedly
      normal with little exception. IR was documented, however, based on the presence
      of the metabolic syndrome and an elevated homeostasis model assessment of IR. We
      posit that this IR is central to the pathogenesis of our patient's lesion, and
      this may explain other cases of DN with normoglycemia. The literature supporting
      this concept is discussed. 

PMID- 25076964
TI  - Molecular pathways underpinning ethanol-induced neurodegeneration.
AB  - While genetics impacts the type and severity of damage following developmental
      ethanol exposure, little is currently known about the molecular pathways that
      mediate these effects. Traditionally, research in this area has used a candidate
      gene approach and evaluated effects on a gene-by-gene basis. Recent studies,
      however, have begun to use unbiased approaches and genetic reference populations
      to evaluate the roles of genotype and epigenetic modifications in phenotypic
      changes following developmental ethanol exposure, similar to studies that
      evaluated numerous alcohol-related phenotypes in adults. Here, we present work
      assessing the role of genetics and chromatin-based alterations in mediating
      ethanol-induced apoptosis in the developing nervous system. Utilizing the
      expanded family of BXD recombinant inbred mice, animals were exposed to ethanol
      at postnatal day 7 via subcutaneous injection (5.0 g/kg in 2 doses). Tissue was
      collected 7 h after the initial ethanol treatment and analyzed by activated
      caspase-3 immunostaining to visualize dying cells in the cerebral cortex and
      hippocampus. In parallel, the levels of two histone modifications relevant to
      apoptosis, gammaH2AX and H3K14 acetylation, were examined in the cerebral cortex
      using protein blot analysis. Activated caspase-3 staining identified marked
      differences in cell death across brain regions between different mouse strains.
      Genetic analysis of ethanol susceptibility in the hippocampus led to the
      identification of a quantitative trait locus on chromosome 12, which mediates, at
      least in part, strain-specific differential vulnerability to ethanol-induced
      apoptosis. Furthermore, analysis of chromatin modifications in the cerebral
      cortex revealed a global increase in gammaH2AX levels following ethanol exposure,
      but did not show any change in H3K14 acetylation levels. Together, these findings
      provide new insights into the molecular mechanisms and genetic contributions
      underlying ethanol-induced neurodegeneration. 

PMID- 25076965
TI  - Exposure to hycanthone alters chromatin structure around specific gene functions
      and specific repeats in Schistosoma mansoni.
AB  - Schistosoma mansoni is a parasitic plathyhelminth responsible for intestinal
      schistosomiasis (or bilharzia), a disease affecting 67 million people worldwide
      and causing an important economic burden. The schistosomicides hycanthone, and
      its later proxy oxamniquine, were widely used for treatments in endemic areas
      during the twentieth century. Recently, the mechanism of action, as well as the
      genetic origin of a stably and Mendelian inherited resistance for both drugs was
      elucidated in two strains. However, several observations suggested early on that
      alternative mechanisms might exist, by which resistance could be induced for
      these two drugs in sensitive lines of schistosomes. This induced resistance
      appeared rapidly, within the first generation, but was metastable (not stably
      inherited). Epigenetic inheritance could explain such a phenomenon and we
      therefore re-analyzed the historical data with our current knowledge of
      epigenetics. In addition, we performed new experiments such as ChIP-seq on
      hycanthone treated worms. We found distinct chromatin structure changes between
      sensitive worms and induced resistant worms from the same strain. No specific
      pathway was discovered, but genes in which chromatin structure modifications were
      observed are mostly associated with transport and catabolism, which makes sense
      in the context of the elimination of the drug. Specific differences were observed
      in the repetitive compartment of the genome. We finally describe what types of
      experiments are needed to understand the complexity of heritability that can be
      based on genetic and/or epigenetic mechanisms for drug resistance in
      schistosomes. 

PMID- 25076966
TI  - Quantitative assessment and validation of network inference methods in
      bioinformatics.

PMID- 25076967
TI  - microRNAs in mycobacterial disease: friend or foe?
AB  - As the role of microRNA in all aspects of biology continues to be unraveled, the
      interplay between microRNAs and human disease is becoming clearer. It should come
      of no surprise that microRNAs play a major part in the outcome of infectious
      diseases, since early work has implicated microRNAs as regulators of the immune
      response. Here, we provide a review on how microRNAs influence the course of
      mycobacterial infections, which cause two of humanity's most ancient infectious
      diseases: tuberculosis and leprosy. Evidence derived from profiling and
      functional experiments suggests that regulation of specific microRNAs during
      infection can either enhance the immune response or facilitate pathogen immune
      evasion. Now, it remains to be seen if the manipulation of host cell microRNA
      profiles can be an opportunity for therapeutic intervention for these difficult
      to-treat diseases. 

PMID- 25076963
TI  - Incorporating epigenetic data into the risk assessment process for the toxic
      metals arsenic, cadmium, chromium, lead, and mercury: strategies and challenges.
AB  - Exposure to toxic metals poses a serious human health hazard based on ubiquitous
      environmental presence, the extent of exposure, and the toxicity and disease
      states associated with exposure. This global health issue warrants accurate and
      reliable models derived from the risk assessment process to predict disease risk
      in populations. There has been considerable interest recently in the impact of
      environmental toxicants such as toxic metals on the epigenome. Epigenetic
      modifications are alterations to an individual's genome without a change in the
      DNA sequence, and include, but are not limited to, three commonly studied
      alterations: DNA methylation, histone modification, and non-coding RNA
      expression. Given the role of epigenetic alterations in regulating gene and thus
      protein expression, there is the potential for the integration of toxic metal
      induced epigenetic alterations as informative factors in the risk assessment
      process. In the present review, epigenetic alterations induced by five high
      priority toxic metals/metalloids are prioritized for analysis and their possible
      inclusion into the risk assessment process is discussed. 

PMID- 25076968
TI  - Monitoring regulation of DNA repair activities of cultured cells in-gel using the
      comet assay.
AB  - Base excision repair (BER) is the predominant cellular mechanism by which human
      cells repair DNA base damage, sites of base loss, and DNA single strand breaks of
      various complexity, that are generated in their thousands in every human cell per
      day as a consequence of cellular metabolism and exogenous agents, including
      ionizing radiation. Over the last three decades the comet assay has been employed
      in scientific research to examine the cellular response to these types of DNA
      damage in cultured cells, therefore revealing the efficiency and capacity of BER.
      We have recently pioneered new research demonstrating an important role for post
      translational modifications (particularly ubiquitylation) in the regulation of
      cellular levels of BER proteins, and that subtle changes (~20-50%) in protein
      levels following siRNA knockdown of E3 ubiquitin ligases or deubiquitylation
      enzymes can manifest in significant changes in DNA repair capacity monitored
      using the comet assay. For example, we have shown that the E3 ubiquitin ligase
      Mule, the tumor suppressor protein ARF, and the deubiquitylation enzyme USP47
      modulate DNA repair by controlling cellular levels of DNA polymerase beta, and
      also that polynucleotide kinase phosphatase levels are controlled by ATM
      dependant phosphorylation and Cul4A-DDB1-STRAP-dependent ubiquitylation. In these
      studies we employed a modification of the comet assay whereby cultured cells,
      following DNA damage treatment, are embedded in agarose and allowed to repair in
      gel prior to lysis and electrophoresis. Whilst this method does have its
      limitations, it avoids the extensive cell culture-based processing associated
      with the traditional approach using attached cells and also allows for the
      examination of much more precise DNA repair kinetics. In this review we will
      describe, using this modified comet assay, our accumulating evidence that
      ubiquitylation-dependant regulation of BER proteins has important consequences
      for overall cellular DNA repair capacity. 

PMID- 25076969
TI  - Mesenchymal stem cells transplantation for neuroprotection in preterm infants
      with severe intraventricular hemorrhage.
AB  - Severe intraventricular hemorrhaging (IVH) in premature infants and subsequent
      posthemorrhagic hydrocephalus (PHH) causes significant mortality and life-long
      neurological complications, including seizures, cerebral palsy, and developmental
      retardation. However, there are currently no effective therapies for neonatal
      IVH. The pathogenesis of PHH has been mainly explained by inflammation within the
      subarachnoid spaces due to the hemolysis of extravasated blood after IVH.
      Obliterative arachnoiditis, induced by inflammatory responses, impairs
      cerebrospinal fluid (CSF) resorption and subsequently leads to the development of
      PHH with ensuing brain damage. Increasing evidence has demonstrated potent
      immunomodulating abilities of mesenchymal stem cells (MSCs) in various brain
      injury models. Recent reports of MSC transplantation in an IVH model of newborn
      rats demonstrated that intraventricular transplantation of MSCs downregulated the
      inflammatory cytokines in CSF and attenuated progressive PHH. In addition, MSC
      transplantation mitigated the brain damages that ensue after IVH and PHH,
      including reactive gliosis, cell death, delayed myelination, and impaired
      behavioral functions. These findings suggest that MSCs are promising therapeutic
      agents for neuroprotection in preterm infants with severe IVH. 

PMID- 25076970
TI  - Psychosocial adjustment and quality of life of adolescents and adults with
      congenital heart disease.
AB  - The incidence of people living with congenital heart disease (CHD) has been
      increasing every year owing to remarkable advances in surgical and catheter
      intervention techniques and devices, and improved knowledge of critical care for
      patients with CHD. However, these patients continue to face physical,
      psychosocial, and environmental challenges, and a number of studies have shown
      higher rates of depression and anxiety disorders than the general population. To
      improve psychosocial functioning and quality of life for adults with CHD, health
      care providers are recommended to inform CHD patients of an accurate diagnosis,
      and overall treatment process, beginning in adolescence to facilitate a smooth
      transition from adolescence to adulthood. Active cooperation with psychiatrists,
      psychologists, social workers, chaplains, and family members is highly
      recommended to help CHD patients feel normal and optimistic and to promote good
      social interactions, close family relationships, and a strong sense of coherence.

PMID- 25076971
TI  - Clinical outcome of acute necrotizing encephalopathy in related to involving the
      brain stem of single institution in Korea.
AB  - PURPOSE: Acute necrotizing encephalopathy (ANE) is a fulminant disease of the
      brain characterized by bilateral thalamic lesions, and is prevalent among
      children in East Asia. The prognosis of ANE is usually poor with a high mortality
      rate and neurological sequelae. This study aimed to delineate the clinical
      characteristics and prognostic factors of ANE. METHODS: We retrospectively
      analyzed clinical data of 399 pediatric patients with encephalitis who were
      admitted to Samsung Medical Center from December 1998 to March 2011. We enrolled
      ten patients (11 cases) with ANE and analyzed their demographic, clinical, and
      neuroimaging data. The location and extent of the brain regions were checked
      based on fluid-attenuated inversion recovery, T1-, and T2-weighted imaging
      findings; the presence of contrast enhancement, restricted diffusion, and
      hemorrhage. RESULTS: Ten patients were identified, including one patient with two
      episodes. The median age of onset was 1.5 years (0.4-8.4 years). The mortality
      rate was 40%, and only 30% of patients survived without neurological sequelae.
      The definite involvement of the brainstem on brain magnetic resonance imaging was
      significantly correlated with mortality (P=0.04). CONCLUSION: Broad and extensive
      brainstem involvement suggested the fulminant course of ANE. Early diagnosis of
      ANE before brainstem involvement, through careful identification of symptoms of
      brain dysfunction, may be the best way to achieve better neurological outcomes.

PMID- 25076972
TI  - Increased risk of refractory Mycoplasma pneumoniae pneumonia in children with
      atopic sensitization and asthma.
AB  - PURPOSE: A nationwide outbreak of Mycoplasma pneumoniae pneumonia (MP) refractory
      to macrolide antibiotics occurred in Korea during 2011. Steroid therapy has been
      reported to be both efficacious and well tolerated in pediatric patients with
      refractory MP. We compared clinical features and laboratory characteristics
      between children with refractory MP requiring steroid treatment and those with
      macrolide-responsive MP and evaluated the risk factors associated with refractory
      MP. METHODS: We investigated 203 children who were admitted to our institution
      with MP from June to November 2011. Refractory MP was defined by persistent fever
      over 38.3C with progressive pulmonary consolidation or pleural effusion despite
      administration of appropriate macrolide antibiotics for 5 days or longer after
      admission. Steroid therapy was initiated on the fifth day after admission for
      refractory cases. RESULTS: There were 26 patients with refractory MP requiring
      steroid therapy. The mean duration of steroid therapy was 5.4 days and most of
      the patients were afebrile within 24 hours after initiation of steroid therapy.
      The prevalence of refractory MP was higher in patients with pleural effusion,
      lobar pneumonia affecting more than 2 lobes, higher levels of serum lactate
      dehydrogenase, increased oxygen requirements, and longer duration of
      hospitalization. Atopic sensitization and history of asthma were also associated
      with refractory MP after adjusting for age and gender. CONCLUSION: Children with
      refractory MP had more severe pneumonia. Atopic sensitization and history of
      asthma may be risk factors for refractory MP requiring steroid therapy in Korean
      children.

PMID- 25076973
TI  - Clinical experience with (18)F-fluorodeoxyglucose positron emission tomography
      and (123)I-metaiodobenzylguanine scintigraphy in pediatric neuroblastoma:
      complementary roles in follow-up of patients.
AB  - PURPOSE: To evaluate the potential utility of (123)I-metaiodobenzylguanine
      ((123)I-MIBG) scintigraphy and (18)F-fluorodeoxyglucose ((18)F-FDG) positron
      emission tomography (PET) for the detection of primary and metastatic lesions in
      pediatric neuroblastoma (NBL) patients, and to determine whether (18)F-FDG PET is
      as beneficial as (123)I-MIBG imaging. METHODS: We selected 8 NBL patients with
      significant residual mass after operation and who had paired (123)I-MIBG and
      (18)F-FDG PET images that were obtained during the follow-up. We retrospectively
      reviewed the clinical charts and the findings of 45 paired scans. RESULTS: Both
      scans correlated relatively well with the disease status as determined by
      standard imaging modalities during follow-up; the overall concordance rates were
      32/45 (71.1%) for primary tumor sites and 33/45 (73.3%) for bone-bone marrow (BM)
      metastatic sites. In detecting primary tumor sites, (123)I-MIBG might be superior
      to (18)F-FDG PET. The sensitivity of (123)I-MIBG and (18)F-FDG PET were 96.7% and
      70.9%, respectively, and their specificity were 85.7% and 92.8%, respectively.
      (18)F-FDG PET failed to detect 9 true NBL lesions in 45 follow-up scans (false
      negative rate, 29%) with positive (123)I-MIBG. For bone-BM metastatic sites, the
      sensitivity of (123)I-MIBG and (18)F-FDG PET were 72.7% and 81.8%, respectively,
      and the specificity were 79.1% and 100%, respectively. (123)I-MIBG scan showed
      higher false positivity (20.8%) than (18)F-FDG PET (0%). CONCLUSION: (123)I-MIBG
      is superior for delineating primary tumor sites, and (18)F-FDG PET could aid in
      discriminating inconclusive findings on bony metastatic NBL. Both scans can be
      complementarily used to clearly determine discrepancies or inconclusive findings
      on primary or bone-BM metastatic NBL during follow-up.

PMID- 25076974
TI  - Two adolescent patients with coexistent Graves' disease and Moyamoya disease in
      Korea.
AB  - Moyamoya disease is a cerebrovascular condition that results in the narrowing of
      the vessels of the circle of Willis and collateral vessel formation at the base
      of the brain. Although relationships between Graves' disease and cerebrovascular
      accidents in Moyamoya disease are obscure, the coexistence of the two diseases is
      noteworthy. Moyamoya disease has been rarely reported in adolescent patients with
      thyrotoxicosis. Recently, we encountered two adolescent Korean patients with
      Moyamoya disease associated with Graves' disease who presented with episodic
      right-sided hemiparesis and syncope. These two girls who had Graves' disease had
      no history of other diseases or head trauma. A thyroid function test revealed a
      euthyroid state and a high thyroid-stimulating hormone (TSH) receptor antibody
      titer at that time. The patients were diagnosed with Moyamoya disease based on
      brain magnetic resonance angiography and cerebral four-vessel angiography. The
      patients underwent cranial revascularization by encephalo-duroarterio-synangiosis
      as soon as a diagnosis was made, which resulted in successful symptom resolution.
      They fared well and had no additional neurological symptoms as of their last
      follow-up visits. Here, we report these two cases of confirmed Moyamoya disease
      complicated by Graves' disease with a review of the literature, and discuss the
      possible association between the two diseases. To our knowledge, this is the
      first report in South Korea on Moyamoya disease associated with Graves' disease
      in adolescents with a euthyroid. 

PMID- 25076975
TI  - A chromosome 1q44 deletion in a 4-month-old girl; The first report in Korea.
AB  - The deletion of the distal long arm of chromosome 1 is associated with a
      characteristic facial appearance and a pattern of associated malformations.
      Characteristic manifestations include a round face with prominent 'cupid's bow'
      and downturned corners of the mouth, thin vermilion borders of lips, a long upper
      lip with a smooth philtrum, a short and broad nose, epicanthal folds, apparently
      low-set ears, micrognathia, microcephaly, abnormal hands and feet, variable
      cardiac or genital anomalies, moderate to severe mental retardation, and growth
      retardation. Using fluorescent in situ hybridization (FISH) analysis to map
      precisely the deletion, we present a case of chromosome 1q44 deletion with
      craniofacial characteristics, multiple congenital anomalies, and growth and
      psychomotor retardation. In comparison with other reported cases of 1q43-44
      deletion, the subject does not show hydrocephalus, seizure, syn- or polydactyly
      of hands, and a urogenital anomaly. However, an arachnoid cyst, pinpoint dimple
      on the midline of the forehead, a right-sided supernumerary nipple and auricular
      pit, polydactyly of the right foot, adducted thumb, and flexion restriction of
      the proximal interphalangeal joint with a simian line in both hands were observed
      additionally. 

PMID- 25076976
TI  - Evaluation of the International Child Development Programme (ICDP) as a community
      wide parenting programme.
AB  - BACKGROUND: Many parenting programmes lack proper evaluation, especially under
      community-wide implementation. OBJECTIVE: Examining the effectiveness of the
      eight-week International Child Development Programme (ICDP), implemented as a
      general programme. METHODOLOGY: Non-clinical caregivers attending ICDP (N = 141)
      and a non-attending community comparison group (N = 79) completed questionnaires
      on parenting, psychosocial functioning, and child difficulties before and after
      ICDP course. Analyses compare changes in scores for both groups over time.
      RESULTS: The ICDP group showed more positive attitudes towards child management
      and reported better child management, improved parental strategies and less
      impact of child difficulties. Caregivers with low initial scores benefited most.
      The comparison group showed little change with a significant decrease in scores
      on the caregiver-child activity scale. DISCUSSION: The results suggest that
      caregivers in the community who do not show clinical signs or have children with
      behaviour or other disorders, may benefit from participating in parent training
      based on ICDP.

PMID- 25076978
TI  - Autism and Dyslexia: A Glance Over 25 Years of Research.
AB  - AUTISM AND DYSLEXIA ARE WRONGLY CLASSIFIED AS CHILDHOOD DISORDERS: They are
      lifelong and therefore have to be studied in adults as well as in children.
      Individual variability is enormous, and, as a result, behavioral diagnosis
      remains problematic. The study of the underlying cognitive abilities in autism
      and dyslexia has acted as a gateway for the emergence of developmental cognitive
      neuroscience.

PMID- 25076977
TI  - Mapping Mental Function to Brain Structure: How Can Cognitive Neuroimaging
      Succeed?
AB  - The goal of cognitive neuroscience is to identify the mapping between brain
      function and mental processing. In this article, I examine the strategies that
      have been used to identify such mappings and argue that they may be fundamentally
      unable to identify selective structure-function mappings. To understand the
      functional anatomy of mental processes, it will be necessary for researchers to
      move from the brain-mapping strategies that the field has employed toward a
      search for selective associations. This will require a greater focus on the
      structure of cognitive processes, which can be achieved through the development
      of formal ontologies that describe the structure of mental processes. In this
      article, I outline the Cognitive Atlas Project, which is developing such
      ontologies, and show how this knowledge could be used in conjunction with data
      mining approaches to more directly relate mental processes and brain function. 

PMID- 25076979
TI  - Breadth-Based Models of Women's Underrepresentation in STEM Fields: An
      Integrative Commentary on Schmidt (2011) and Nye et al. (2012).
AB  - Relative strength of math and verbal abilities and interests drive science,
      technology, engineering, and math (STEM) career choices more than absolute math
      ability alone. Having one dominant aptitude (e.g., for mathematics) increases the
      likelihood of a strong self-concept in that domain and decreases the likelihood
      of equivocation about career choices in comparison with individuals with
      equivalent mathematical aptitude who have comparable strength in non-math areas.
      Males are more likely than females to have an asymmetrical cognitive profile of
      higher aptitude in math relative to verbal domains. Together, these two points
      suggest that the academic and career pursuits of high math ability males may be
      attributable to their narrower options among STEM fields, whereas females' more
      symmetrical cognitive profile means their math and verbal interests compete in
      the formation of their ability self-concept and, hence, in their broader career
      choices. Such equivocation about STEM careers is in fact already evident in girls
      with high math aptitude as early as junior high school. Thus, we argue that
      asymmetry in interests and aptitudes is an underappreciated factor in sex
      differences in career choice. To the extent this is true, focusing on
      strengthening young women's STEM-related abilities and ability self-concepts to
      increase female STEM representation may be an unproductive approach; to increase
      representation, it may be more effective to focus on harvesting the potential of
      those girls and women whose breadth of interest and high ability spans
      social/verbal and spatial/numerical domains. The use of interventions that play
      to this greater breadth by socially contextualizing STEM is one potential
      solution. 

PMID- 25076980
TI  - Emergency primary repair of grade V bladder neck injury complicating pelvic
      fracture.
AB  - We report a case of a grade V bladder injury complicating an open-book pelvic
      fracture following a road traffic accident. The bladder neck injury was primarily
      repaired in the emergency setting of a poor-resourced area with successful
      outcome. The dangers of urinary extravasation are still to be considered of
      importance and we advocate and encourage immediate/emergency open intervention
      although it remains controversial to say the least in a lesser resourced
      healthcare set up. 

PMID- 25076981
TI  - Gender-based violence in conflict and displacement: qualitative findings from
      displaced women in Colombia.
AB  - INTRODUCTION: Gender-based violence (GBV) is prevalent among, though not specific
      to, conflict affected populations and related to multifarious levels of
      vulnerability of conflict and displacement. Colombia has been marked with decades
      of conflict, with an estimated 5.2 million internally displaced persons (IDPs)
      and ongoing violence. We conducted qualitative research to understand the
      contexts of conflict, displacement and dynamics with GBV. This as part of a multi
      phase, mixed method study, in collaboration with UNHCR, to develop a screening
      tool to confidentially identify cases of GBV for referral among IDP women who
      were survivors of GBV. METHODS: Qualitative research was used to identify the
      range of GBV, perpetrators, contexts in conflict and displacement, barriers to
      reporting and service uptake, as well as to understand experiences of service
      providers. Thirty-five female IDPs, aged 18 years and older, who self-identified
      as survivors of GBV were enrolled for in-depth interviews in San Jose de Guaviare
      and Quibdo, Colombia in June 2012. Thirty-one service providers participated in
      six focus group discussions and four interviews across these sites. RESULTS:
      Survivors described a range of GBV across conflict and displacement settings.
      Armed actors in conflict settings perpetrated threats of violence and harm to
      family members, child recruitment, and, to a lesser degree, rape and forced
      abortion. Opportunistic violence, including abduction, rape, and few accounts of
      trafficking were more commonly reported to occur in the displacement setting,
      often perpetrated by unknown individuals. Intrafamilial violence, intimate
      partner violence, including physical and sexual violence and reproductive control
      were salient across settings and may be exacerbated by conflict and displacement.
      Barriers to reporting and services seeking were reported by survivors and
      providers alike. CONCLUSIONS: Findings highlight the need for early
      identification of GBV cases, with emphasis on confidential approaches and active
      engagement of survivors in available, quality services. Such efforts may
      facilitate achievement of the goals of new Colombian laws, which seek to prevent
      and respond to GBV, including in conflict settings. Ongoing conflict and
      generalized GBV in displacement, as well as among the wider population, suggests
      a need to create sustainable solutions that are accessible to both IDPs and
      general populations.

PMID- 25076982
TI  - Novel Gene Discovery in the Human Malaria Parasite using Nucleosome Positioning
      Data.
AB  - Recent genome-wide studies on nucleosome positioning in model organisms have
      shown strong evidence that nucleosome landscapes in the proximity of protein
      coding genes exhibit regular characteristic patterns. Here, we propose a
      computational framework to discover novel genes in the human malaria parasite
      genome P. falciparum using nucleosome positioning inferred from MAINE-seq data.
      We rely on a classifier trained on the nucleosome landscape profiles of
      experimentally verified genes, and then used to discover new genes (without
      considering the primary DNA sequence). Cross-validation experiments show that our
      classifier is very accurate. About two thirds of the locations reported by the
      classifier match experimentally determined expressed sequence tags in GenBank,
      for which no gene has been annotated in the human malaria parasite.

PMID- 25076983
TI  - The Engagement Interview Protocol (EIP): improving the acceptance of mental
      health treatment among Chinese immigrants.
AB  - Many depressed Chinese immigrants are unfamiliar with Western psychiatric
      terminology and have high levels of stigma toward psychiatric illnesses, making
      it difficult to engage them into psychiatric treatment. We have designed the
      Engagement Interview Protocol (EIP), a semi-standardized protocol that
      incorporates cultural components to a standard psychiatric evaluation. The EIP
      elicits patients' narratives and uses anthropological questions to explore
      patients' illness beliefs, which are integrated with patients' information on
      medical and psychiatric history, psychosocial background and mental status
      examination so that treatment options can be negotiated in a culturally sensitive
      manner. In our field testing on depressed Chinese immigrants, the EIP model was
      found to be a practical tool that can be completed within the allotted one-hour
      time frame and was highly effective in facilitating the enrollment of patients in
      treatment for depression. The EIP is a concise, time-effective, user-friendly
      protocol that can be used both in research and real-world clinical settings with
      diverse patient populations.

PMID- 25076984
TI  - Phenotypic and genetic characterization of a patient with a de novo interstitial
      14q24.1q24.3 deletion.
AB  - BACKGROUND: Interstitial deletions of chromosome bands 14q24.1q24.3 are very rare
      with only three reported cases. RESULTS: We describe a 7-year-old boy with a
      5.345 Mb de novo interstitial deletion at 14q24.1q24.3 band detected by array-CGH
      who had a complex phenotype characterized by seizures, congenital heart defects,
      dysmorphisms, psychomotor delay, and bronchopulmonary, skeletal, and brain
      anomalies. CONCLUSION: The deleted region contains numerous genes, but we focused
      our attention on three of them (C14orf169, NUMB, and PSEN1), which could account,
      at least partially, for the phenotype of the boy. We therefore discuss the
      involvement of these genes and the observed phenotype compared to that of
      previously described patients.

PMID- 25076985
TI  - First complex, then simple.

PMID- 25076986
TI  - Genome sequencing of multidrug resistant novel Clostridium sp. BL8 reveals its
      potential for pathogenicity.
AB  - BACKGROUND: The human gut microbiome is important for maintaining the health
      status of the host. Clostridia are key members of the human gut microbiome,
      carrying out several important functions in the gut environment. Hence
      understanding the role of different Clostridium species isolated from human gut
      is essential. The present study was aimed at investigating the role of novel
      Clostridium sp. isolate BL8 in human gut using genome sequencing as a tool.
      FINDINGS: The genome analysis of Clostridium sp. BL8 showed the presence of
      several adaptive features like bile resistance, presence of sensory and
      regulatory systems, presence of oxidative stress managing systems and presence of
      membrane transport systems. The genome of Clostridium sp. BL8 consists of a wide
      variety of virulence factors like phospholipase C (alpha toxin), hemolysin,
      aureolysin and exfoliative toxin A, as well as adhesion factors, proteases, Type
      IV secretion system and antibiotic resistance genes. In vitro antibiotic
      sensitivity testing showed that Clostridium sp. BL8 was resistant to 11 different
      tested antibiotics belonging to 6 different classes. The cell cytotoxicity assay
      confirmed the cytotoxic effect of Clostridium sp. BL8 cells, which killed 40% of
      the Vero cells after 4 hrs of incubation. CONCLUSIONS: Clostridium sp. BL8 has
      adapted for survival in human gut environment, with presence of different
      adaptive features. The presence of several virulence factors and cell cytotoxic
      activity indicate that Clostridium sp. BL8 has a potential to cause infections in
      humans, however further in vivo studies are necessary to ascertain this fact.

PMID- 25076988
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Pregnancy in pulmonary hypertension.
AB  - Pregnancy in pulmonary hypertension (PH) is known to be associated with high
      morbidity and mortality. The physiological changes occur during normal pregnancy,
      such as increase blood volume and cardiac output (CO) may be detrimental in PH
      patients. Several practice guidelines advise against pregnancy and even recommend
      termination of pregnancy. Occasionally PH may be diagnosed for the first time
      during pregnancy, as stress of pregnancy can unmask previously undiagnosed PH in
      an asymptomatic individual. This narrative review provides a detailed discussion
      about the physiologic parameters associated in pregnancy and their negative
      effect on the right ventricle. It also gives practical evidence-based
      recommendations about different management issues in PH pregnant patients. 

PMID- 25076987
TI  - Saudi guidelines on the diagnosis and treatment of pulmonary hypertension: 2014
      updates.
AB  - The Saudi Association for Pulmonary Hypertension (previously called Saudi
      Advisory Group for Pulmonary Hypertension) has published the first Saudi
      Guidelines on Diagnosis and Treatment of Pulmonary Arterial Hypertension back in
      2008.[1] That guideline was very detailed and extensive and reviewed most aspects
      of pulmonary hypertension (PH). One of the disadvantages of such detailed
      guidelines is the difficulty that some of the readers who just want to get a
      quick guidance or looking for a specific piece of information might face. All
      efforts were made to develop this guideline in an easy-to-read form, making it
      very handy and helpful to clinicians dealing with PH patients to select the best
      management strategies for the typical patient suffering from a specific
      condition. This Guideline was designed to provide recommendations for problems
      frequently encountered by practicing clinicians involved in management of PH.
      This publication targets mainly adult and pediatric PH-treating physicians, but
      can also be used by other physicians interested in PH. 

PMID- 25076989
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Pulmonary hypertension in children.
AB  - Pulmonary hypertension (PH) is relatively uncommon in children. Pulmonary
      arterial hypertension (PAH) in pediatric comprises a wide spectrum of diseases,
      from a transient neonatal condition to a progressive disease associated with
      morbidity and mortality. Most common PAH in pediatric are idiopathic (IPAH) or
      PAH associated with congenital heart disease (PAH-CHD), while other associated
      conditions, such as connective tissue disease (CTD), are less common in
      pediatrics. Despite better understanding of PH and the availability of new
      medications during recent decades; the diagnosis, investigation and choice of
      therapy remain a challenge in children, as evidence-based recommendations depend
      mainly on adult studies. In this review, we provide a detailed discussion about
      the distinctive features of PAH in pediatric, mainly emphacysing on
      classification and diagnostic algorithm. 

PMID- 25076990
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Intensive care management of pulmonary hypertension.
AB  - Pulmonary hypertension (PH) in the Intensive Care Unit (ICU) may be due to
      preexisting pulmonary vascular lung disease, liver disease, or cardiac diseases.
      PH also may be caused by critical illnesses, such as acute respiratory distress
      syndrome (ARDS), acute left ventricular dysfunction and pulmonary embolism, or
      may occur after cardiac or thoracic surgery. Regardless of the underlying cause
      of PH, the final common pathway for hemodynamic deterioration and death is RV
      failure, which is the most challenging aspect of patient management. Therapy is
      thus aimed at acutely relieving RV overload by decreasing PVR and reversing RV
      failure with pulmonary vasodilators and inotropes. 

PMID- 25076991
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Challenges in managing pulmonary hypertension in the developing countries.
AB  - There is scant published data about pulmonary hypertension (PH) from the
      developing countries. True prevalence of the disease, its biology, etiology and
      response to treatment are not well known, and they are likely to be somewhat
      different from that of the developed countries. In this review, we will discuss
      the main challenges for managing PH in developing countries and propose real-life
      recommendations to deal with such difficulties. 

PMID- 25076992
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Genetics of pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is a phenotype characterized by functional and
      structural changes in the pulmonary vasculature, leading to increased vascular
      resistance.[12] The World Health Organization has classified PH into five
      different types: arterial, venous, hypoxic, thromboembolic or miscellaneous;
      details are available in the main guidelines. Group I of this classification,
      designated as pulmonary arterial hypertension (PAH), will remain the main focus
      here. The pathophysiology involves signaling, endothelial dysfunction, activation
      of fibroblasts and smooth muscle cells, interaction between cells within the
      vascular wall, and the circulating cells; as a consequence plexiform lesions are
      formed, which is common to both idiopathic and heritable PAH but are also seen in
      other forms of PAH.[234] As the pathology of PAH in the lung is well known, this
      article focuses on the genetic aspects associated with the disease and is a gist
      of several available articles in literature. 

PMID- 25076993
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Pulmonary arterial hypertension associated with congenital heart disease.
AB  - Congenital heart disease (CHD) with intracardiac/extracardiac shunts is an
      important etiology of pulmonary arterial hypertension (PAH). The majority of
      children with congenital cardiac shunts do not develop advanced pulmonary
      vasculopathy, as surgical repair of the anomalies is now performed early in life.
      However, if not repaired early, some defects will inevitably lead to pulmonary
      vascular disease (truncus arteriosus, transposition of the great arteries
      associated with a ventricular septal defect (VSD), atrioventricular septal
      defects remarkably in Down syndrome, large, nonrestrictive VSDs, patent ductus
      arteriosus and related anomalies). The majority of patients are now assigned to
      surgery based on noninvasive evaluation only. PAH becomes a concern (requiring
      advanced diagnostic procedures) in about 2-10% of them. In adults with CHD, the
      prevalence of advanced pulmonary vasculopathy (Eisenmenger syndrome) is around 4
      12%.[1] This article will discuss the diagnostic and management approach for PAH
      associated with CHD (PAH-CHD). 

PMID- 25076995
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Schistosomiasis and pulmonary arterial hypertension.
AB  - Schistosomiasis is caused by infection with the parasite Schistosoma, which is a
      flat-worm or fluke. The dominant species are Schistosoma mansoni, Schistosoma
      japonicum, and Schistosoma haematobium. Schistosomiasis is the third most common
      parasitic disease in the world after malaria and amoebiasis. It is endemic in
      more than 70 countries affecting about 200 million people worldwide, of whom 80%
      are in sub-Saharan Africa. There are pockets of infection in north-eastern
      Brazil, near the Yangtze River in China, and some pockets in south East Asia. In
      the East Mediterranean regions, the Schistosoma have been reported in Iraq and
      Egypt as well as in Sudan. The latter has the highest infection rate nowadays,
      particularly in the Al Jazeera area, due to the poor Schistosoma control program.
      In the Arabian peninsula, schistosomiasis has been reported in southwest part of
      Saudi Arabia, mainly in the Asir province and Jizan province, which lay in the
      southwest corner of Saudi Arabia and directly north of the border with Yemen. The
      efforts to control schistosomiasis have been very successful in Saudi Arabia due
      to the irrigation system control. However, the infection is prone in Yemen, where
      the schistosomiasis control is much less strict. Thus as a result, the problem
      still exists due to transmigration of the populations from both countries. As a
      cause of pulmonary arterial hypertension (PAH), schistosomiasis is still under
      diagnosed and undertreated. This article with give a highlight about the
      pathophysiology of the disease and both diagnostic and therapeutic strategies. 

PMID- 25076994
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Pulmonary arterial hypertension associated with connective tissue diseases.
AB  - The explosive growth of medical literature on pulmonary hypertension (PH) has led
      to a steady increase in awareness of this disease within the medical community
      during the past decade. The recent revision of the classification of PH is
      presented in in the main guidelines. Group 1 PH or pulmonary arterial
      hypertension (PAH) is a heterogeneous group and includes PH due to inheritable,
      drug-induced, and toxin-induced causes and to such underlying systemic causes as
      connective tissue diseases, human immunodeficiency viral infection, portal
      hypertension, congenital heart disease, and schistosomiasis. Systemic sclerosis
      (SSc) is an autoimmune multisystem disorder, which affects over 240 persons per
      million in the United States.[1] Its manifestations are not confined to the skin
      but may also involve the lungs, kidneys, peripheral circulation, musculoskeletal
      system, gastrointestinal tract, and heart. The outcome of PAH associated with SSc
      is worse when compared to other subtypes of PAH. In this review, we summarize
      available information about the pulmonary vascular and cardiac manifestations of
      SSc with special emphasis on their prognostic implications as well as the
      peculiarity of their detection. 

PMID- 25076996
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Portopulmonary hypertension.
AB  - Portopulmonary hypertension (POPH) is defined as pulmonary arterial hypertension
      (PAH) complicated by portal hypertension, with or without advanced hepatic
      disease. Significant percentage of patients with cirrhotic liver disease has high
      cardiac output and subsequently elevated pulmonary arterial pressures (PAP).
      However, patients with POPH develop a progressive increase in pulmonary vascular
      resistance (PVR), which is generally lower than that observed in other forms of
      PAH. The prognosis of untreated patients with POPH is very poor and the outcome
      of liver transplant (LT) in those patients is determined by the degree of
      severity of the associated pulmonary hemodynamics. In this narrative review, we
      describe the clinical presentation of POPH, the pathobiology, and the clinical
      implication of pulmonary hemodynamics. We also provide evidence-based
      recommendations for the diagnosic and management approaches of POPH. 

PMID- 25076997
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Pulmonary hypertension due to left heart disease.
AB  - Pulmonary hypertension (PH) due to left heart disease is the most common cause of
      pulmonary hypertension in the western world. It is classified as WHO PH group II.
      Different pathophysiologic abnormalities may take place in this condition,
      including pulmonary venous congestion and vascular remodeling. Despite the high
      prevalence of WHO group 2 PH, the major focus of research on PH over the past
      decade has been on WHO group 1 pulmonary arterial hypertension (PAH). Few
      investigators have focused on WHO group 2 PH; consequently, the pathophysiology
      of this condition remains poorly understood, and no specific therapy is
      available. Clinical and translational studies in this area are much needed and
      have the potential to positively affect large numbers of patients. In this
      review, we provide a detailed discussion upon the pathophysiology of the disease,
      the recent updates in classification, and the diagnostic and therapeutic
      algorithms. 

PMID- 25076998
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Pulmonary hypertension due to lung diseases and/or hypoxia.
AB  - Chronic lung diseases are common causes of pulmonary hypertension. It ranks
      second after the left heart disease. Both obstructive and restrictive lung
      diseases are know to cause pulmonary hypertension. The pathophysiology of the
      disease is complex, and includes factors affecting the blood vessels, airways,
      and lung parenchyma. Hypoxia and the inhalation of toxic materials are another
      contributing factors. Recent guidelines have further clarified the association
      between pulmonary hypertension and chronic lung disease and made general
      guidelines concerning the diagnosis and management. In this article, we will
      provide a detailed revision about the new classification and give general
      recommendations about the management of pulmonary hypertension in chronic lung
      diseases. 

PMID- 25076999
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is categorized as group IV
      in the WHO classification for pulmonary hypertension. The disease requires a very
      low index of suspicion for identification and needs a special diagnostic approach
      utilizing clinical, radiological, and hemodynamic tools. As CTEPH is potentially
      curable, all efforts should be consumed to reach the accurate diagnosis and
      subsequently evaluated for operability. Although pulmonary endarterectomy (PEA)
      is the only curative tool so far, recent updates concerning medical and
      interventional therapy have made significant advances in inoperable patients. In
      this review, we provide a detailed discussion on diagnostic algorithm, surgical
      operability criteria, PEA, and the medical therapy. 

PMID- 25077000
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Pulmonary hypertension associated with hemolytic anemia.
AB  - Hereditary hemoglobin disorders affecting the globin chain synthesis namely
      thalassemia syndromes and sickle cell disease (SCD) are the most common genetic
      disorders in human. Around 7% of the world population carries genes for these
      disorders, mainly the Mediterranean Basin, Middle and Far East, and Sub-Saharan
      Africa. An estimated 30 million people worldwide are living with sickle cell
      disease, while 60-80 million carry beta thalassemia trait. About 400,000 children
      are born with severe hemoglobinopathies each year. Cardiovascular complications
      of hemoglobinopathies include left and right ventricular (RV) dysfunction,
      arrhythmias, pericarditis, myocarditis, valvular heart disease, myocardial
      ischemia, and notably pulmonary hypertension (PH). Because of a unique
      pathophysiology, pulmonary hypertension associated with hemolytic disorders was
      moved from WHO group I to group V PH diseases. Treatment strategies are also
      unique and include blood transfusion, iron chelation, hydroxyurea, and oxygen
      therapy. The role of PH-specific agents has not been established. 

PMID- 25077001
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      General management for pulmonary hypertension.
AB  - Treatment of pulmonary hypertension (PH) patients is challenging and should only
      be initiated after a comprehensive diagnostic evaluation. Such treatment should
      ideally be done in specialized centers with full capability for hemodynamic
      measurements, having access to a broad range of PAH therapies, and adequate
      experience in the management of critically ill patients. The following discussion
      is intended to review the general measures and the non-specific (supportive)
      therapy used in managing PH patients, while the specific therapy will be
      discussed in a subsequent different article. 

PMID- 25077002
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Medical and surgical management for pulmonary arterial hypertension.
AB  - Prior to the availability of the pulmonary arterial hypertension (PAH)-specific
      therapy, PAH was a dreadful disease with a very poor prognosis. Better
      understanding of the complex pathobiology of PAH has led to a major therapeutic
      evolution. International regulatory agencies have approved many specific drugs
      with different pharmacologic pathways and routes of administration. In the year
      2013, two new drugs with great potentials in managing PAH have been added to the
      treatment options, macitentan and riociguat. Additional drugs are expected to
      come in the near future. A substantial body of evidence has confirmed the
      effectiveness of pulmonary arterial hypertension (PAH)-specific therapies in
      improving the patients' symptomatic status and slowing down the rate of clinical
      deterioration. Although the newer modern medications have significantly improved
      the survival of patients with PAH, it remains a non-curable and fatal disease.
      Lung transplantation (LT) remains the only therapeutic option for selected
      patients with advanced disease who continue to deteriorate despite optimal
      therapy. 

PMID- 25077003
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Biomarkers in pulmonary arterial hypertension.
AB  - The biomarker is an indicaror of a biological or pathological process. Clinical
      observations, measures or environmental events, or measured laboratory values can
      all be biomarkers in the appropriate setting. An ideal biomarker reflects the
      underlying biological process, predicts clinical events, is easily obtainable, is
      reproducible and is not prohibitively expensive. This typically requires
      validation in longitudinal cohort studies. Biomarkers may help understand the
      pathological mechanisms responsible for the disease, help as screening tools,
      predict disease worsening or decline, and determine adequacy of response to
      therapeutic interventions. 

PMID- 25077005
TI  - Synthesis and investigation of new Hesperadin analogues antitumor effects on HeLa
      cells.
AB  - Hesperadin is one of the indolinones that was designed against the ATP-binding
      site of Aurora kinase. This molecule inhibits Aurora B kinase by phosphorylation
      of histone H3. In this study, new derivatives of Hesperadin containing an amide
      group in their structures were synthesized through sequential Ugi/palladium
      catalyzed approach and in vitro antitumor activity of new compounds were
      evaluated by cell proliferation assay. The results show that compounds 6f, 6i,
      6l, and 6o were dose-dependently inhibited in different concentrations, and IC50
      values were between 35 and 43 nM. It seems that lipophilic substitution on the
      indolinone core with the ability to form additional hydrogen bond might lead to
      increased stability of structure and activity of new Hesperadin analogues. 

PMID- 25077007
TI  - JOCB Bulletin.

PMID- 25077004
TI  - Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension:
      Perioperative management in patients with pulmonary hypertension.
AB  - Patients with pulmonary hypertension (PH) are being encountered more commonly in
      the perioperative period and this trend is likely to increase as improvements in
      the recognition, management, and treatment of the disease continue to occur.
      Management of these patients is challenging due to their tenuous hemodynamic
      status. Recent advances in the understanding of the patho-physiology, risk
      factors, monitoring, and treatment of the disease provide an opportunity to
      reduce the morbidity and mortality associated with PH in the peri-operative
      period. Management of these patients requires a multi-disciplinary approach and
      meticulous care that is best provided in centers with vast experience in PH. In
      this review, we provide a detailed discussion about oerioperative strategies in
      PH patients, and give evidence-based recommendations, when applicable. 

PMID- 25077008
TI  - Myositis ossificans mimicking sarcoma, the importance of diagnostic imaging -
      case report.
AB  - BACKGROUND: Myositis ossificans is localized inflammatory process affecting
      skeletal muscles. Very rarely it can affect one of the neck muscles and present
      as a neck tumor, it can be misdiagnosed as the clinical, radiological and
      histological examinations can mimic a sarcoma. CASE REPORT: We report a 29 year
      old female patient with neck tumor suspected to be a sarcoma who underwent full
      diagnostics imaging and open bipsy with histopatological examination, afterwards
      surgical excision was performed. CONCLUSIONS: The aim of this study was to
      present the differential diagnosis based on diagnostics imaging between MO and
      malignant tumors, such as parosteal sarcoma, synovial sarcoma and malignant
      fibrous histiocytoma.

PMID- 25077006
TI  - Synthesis, molecular docking and antibacterial evaluation of new 1,4
      naphthoquinone derivatives contains carbazole-6,11-dione moiety.
AB  - A new series of new 1,4-naphthoquinone derivatives containing carbazole-6,11
      dione moiety, which has not been reported yet, has been synthesized from 1,4
      naphthoquinone and 4-aminophenylsulfone involving a Michael addition,
      benzoylation, and Pd-catalyzed coupling. This set of compounds has been evaluated
      for in vitro antibacterial studies against different Gram-positive and Gram
      negative bacteria, and most of the synthesized compounds exhibited good
      antibacterial activity and the minimum inhibitory concentrations (MICs) are
      compared with the standard drugs used. Compound 7 exhibited good antibacterial
      activity among all the molecules studied with the best MIC of 2.1 MUg/mL against
      Bacillus subtilis. To understand the molecular interactions with targeted
      proteins, the molecular docking of all the synthesized compounds were carried
      out; between 14 molecules docked, compound 7 was the one with the best glide and
      E model score of -7.73 and -95.37, respectively. In all docked molecules,
      compound 5 exhibited least glide and E model score of -4.55 and -101.56,
      respectively. Figure? 

PMID- 25077009
TI  - Chest wall reconstruction in male poland syndrome.

PMID- 25077010
TI  - A "mix-and-match" approach to designing Ca(2+) microdomains at membrane-contact
      sites.
AB  - Ca(2+) microdomains are critical for regulating cellular activity and often form
      at membrane contact sites. Such sites between lysosomes and the ER potentially
      provide a platform for signaling by the Ca(2+) mobilizing messenger NAADP.
      However, at present we know little of how Ca(2+) release events are coordinated
      at these experimentally intractable junctions. We therefore developed a
      computational model of lysosome-ER microdomains, which suggested that small leaks
      of Ca(2+) from the lysosome couple to Ca(2+)-sensitive Ins(1,4,5)P 3 receptors on
      the ER to generate global, microdomain-dependent Ca(2+) signals. Here we discuss
      how the "mix-and-match" arrangement of different Ca(2+) signaling proteins on the
      "source" and "target" membranes might generate functionally heterogeneous Ca(2+)
      microdomains. 

PMID- 25077011
TI  - Intensity Inhomogeneity Correction of Magnetic Resonance Images using Patches.
AB  - This paper presents a patch-based non-parametric approach to the correction of
      intensity inhomogeneity from magnetic resonance (MR) images of the human brain.
      During image acquisition, the inhomogeneity present in the radio-frequency coil,
      is usually manifested on the reconstructed MR image as a smooth shading effect.
      This artifact can significantly deteriorate the performance of any kind of image
      processing algorithm that uses intensities as a feature. Most of the current
      inhomogeneity correction techniques use explicit smoothness assumptions on the
      inhomogeneity field, which sometimes limit their performance if the actual
      inhomogeneity is not smooth, a problem that becomes prevalent in high fields. The
      proposed patch-based inhomogeneity correction method does not assume any
      parametric smoothness model, instead, it uses patches from an atlas of an
      inhomogeneity-free image to do the correction. Preliminary results show that the
      proposed method is comparable to N3, a current state of the art method, when the
      inhomogeneity is smooth, and outperforms N3 when the inhomogeneity contains non
      smooth elements.

PMID- 25077012
TI  - Image-Guided Abdominal Surgery and Therapy Delivery.
AB  - Image-Guided Surgery has become the standard of care in intracranial neurosurgery
      providing more exact resections while minimizing damage to healthy tissue. Moving
      that process to abdominal organs presents additional challenges in the form of
      image segmentation, image to physical space registration, organ motion and
      deformation. In this paper, we present methodologies and results for addressing
      these challenges in two specific organs: the liver and the kidney.

PMID- 25077013
TI  - Language control in bilinguals: The adaptive control hypothesis.
AB  - Speech comprehension and production are governed by control processes. We explore
      their nature and dynamics in bilingual speakers with a focus on speech
      production. Prior research indicates that individuals increase cognitive control
      in order to achieve a desired goal. In the adaptive control hypothesis we propose
      a stronger hypothesis: Language control processes themselves adapt to the
      recurrent demands placed on them by the interactional context. Adapting a control
      process means changing a parameter or parameters about the way it works (its
      neural capacity or efficiency) or the way it works in concert, or in cascade,
      with other control processes (e.g., its connectedness). We distinguish eight
      control processes (goal maintenance, conflict monitoring, interference
      suppression, salient cue detection, selective response inhibition, task
      disengagement, task engagement, opportunistic planning). We consider the demands
      on these processes imposed by three interactional contexts (single language, dual
      language, and dense code-switching). We predict adaptive changes in the neural
      regions and circuits associated with specific control processes. A dual-language
      context, for example, is predicted to lead to the adaptation of a circuit
      mediating a cascade of control processes that circumvents a control dilemma.
      Effective test of the adaptive control hypothesis requires behavioural and
      neuroimaging work that assesses language control in a range of tasks within the
      same individual.

PMID- 25077014
TI  - Selection based on the size of the black tie of the great tit may be reversed in
      urban habitats.
AB  - A standard approach to model how selection shapes phenotypic traits is the
      analysis of capture-recapture data relating trait variation to survival.
      Divergent selection, however, has never been analyzed by the capture-recapture
      approach. Most reported examples of differences between urban and nonurban
      animals reflect behavioral plasticity rather than divergent selection. The aim of
      this paper was to use a capture-recapture approach to test the hypothesis that
      divergent selection can also drive local adaptation in urban habitats. We focused
      on the size of the black breast stripe (i.e., tie width) of the great tit (Parus
      major), a sexual ornament used in mate choice. Urban great tits display smaller
      tie sizes than forest birds. Because tie size is mostly genetically determined,
      it could potentially respond to selection. We analyzed capture/recapture data of
      male great tits in Barcelona city (N = 171) and in a nearby (7 km) forest (N =
      324) from 1992 to 2008 using MARK. When modelling recapture rate, we found it to
      be strongly influenced by tie width, so that both for urban and forest habitats,
      birds with smaller ties were more trap-shy and more cautious than their larger
      tied counterparts. When modelling survival, we found that survival prospects in
      forest great tits increased the larger their tie width (i.e., directional
      positive selection), but the reverse was found for urban birds, with individuals
      displaying smaller ties showing higher survival (i.e., directional negative
      selection). As melanin-based tie size seems to be related to personality, and
      both are heritable, results may be explained by cautious personalities being
      favored in urban environments. More importantly, our results show that divergent
      selection can be an important mechanism in local adaptation to urban habitats and
      that capture-recapture is a powerful tool to test it. 

PMID- 25077016
TI  - An Illumina metabarcoding pipeline for fungi.
AB  - High-throughput metabarcoding studies on fungi and other eukaryotic
      microorganisms are rapidly becoming more frequent and more complex, requiring
      researchers to handle ever increasing amounts of raw sequence data. Here, we
      provide a flexible pipeline for pruning and analyzing fungal barcode (ITS rDNA)
      data generated as paired-end reads on Illumina MiSeq sequencers. The pipeline
      presented includes specific steps fine-tuned for ITS, that are mostly missing
      from pipelines developed for prokaryotes. It (1) employs state of the art
      programs and follows best practices in fungal high-throughput metabarcoding; (2)
      consists of modules and scripts easily modifiable by the user to ensure maximum
      flexibility with regard to specific needs of a project or future methodological
      developments; and (3) is straightforward to use, also in classroom settings. We
      provide detailed descriptions and revision techniques for each step, thus giving
      the user maximum control over data treatment and avoiding a black-box approach.
      Employing this pipeline will improve and speed up the tedious and error-prone
      process of cleaning fungal Illumina metabarcoding data. 

PMID- 25077015
TI  - Different degree of paternal mtDNA leakage between male and female progeny in
      interspecific Drosophila crosses.
AB  - Maternal transmission of mitochondrial DNA (mtDNA) in animals is thought to
      prevent the spread of selfish deleterious mtDNA mutations in the population.
      Various mechanisms have been evolved independently to prevent the entry of sperm
      mitochondria in the embryo. However, the increasing number of instances of
      paternal mtDNA leakage suggests that these mechanisms are not very effective. The
      destruction of sperm mitochondria in mammalian embryos is mediated by nuclear
      factors. Also, the destruction of paternal mitochondria in intraspecific crosses
      is more effective than in interspecific ones. These observations have led to the
      hypothesis that leakage of paternal mtDNA (and consequently mtDNA recombination
      owing to ensuing heteroplasmy) might be more common in inter- than in
      intraspecific crosses and that it should increase with phylogenetic distance of
      hybridizing species. We checked paternal leakage in inter- and intraspecific
      crosses in Drosophila and found little evidence for this hypothesis. In addition,
      we have observed a higher level of leakage among male than among female progeny
      from the same cross. This is the first report of sex-specific leakage of paternal
      mtDNA. It suggests that paternal mtDNA leakage might not be a stochastic result
      of an error-prone mechanism, but rather, it may be under complex genetic control.

PMID- 25077017
TI  - On the fate of seasonally plastic traits in a rainforest butterfly under relaxed
      selection.
AB  - Many organisms display phenotypic plasticity as adaptation to seasonal
      environmental fluctuations. Often, such seasonal responses entails plasticity of
      a whole suite of morphological and life-history traits that together contribute
      to the adaptive phenotypes in the alternative environments. While phenotypic
      plasticity in general is a well-studied phenomenon, little is known about the
      evolutionary fate of plastic responses if natural selection on plasticity is
      relaxed. Here, we study whether the presumed ancestral seasonal plasticity of the
      rainforest butterfly Bicyclus sanaos (Fabricius, 1793) is still retained despite
      the fact that this species inhabits an environmentally stable habitat. Being
      exposed to an atypical range of temperatures in the laboratory revealed hidden
      reaction norms for several traits, including wing pattern. In contrast,
      reproductive body allocation has lost the plastic response. In the savannah
      butterfly, B. anynana (Butler, 1879), these traits show strong developmental
      plasticity as an adaptation to the contrasting environments of its seasonal
      habitat and they are coordinated via a common developmental hormonal system. Our
      results for B. sanaos indicate that such integration of plastic traits - as a
      result of past selection on expressing a coordinated environmental response - can
      be broken when the optimal reaction norms for those traits diverge in a new
      environment. 

PMID- 25077018
TI  - Dual phylogenetic origins of Nigerian lions (Panthera leo).
AB  - Lion fecal DNA extracts from four individuals each from Yankari Game Reserve and
      Kainji-Lake National Park (central northeast and west Nigeria, respectively) were
      Sanger-sequenced for the mitochondrial cytochrome b gene. The sequences were
      aligned against 61 lion reference sequences from other parts of Africa and India.
      The sequence data were analyzed further for the construction of phylogenetic
      trees using the maximum-likelihood approach to depict phylogenetic patterns of
      distribution among sequences. Our results show that Nigerian lions grouped
      together with lions from West and Central Africa. At the smaller geographical
      scale, lions from Kainji-Lake National Park in western Nigeria grouped with lions
      from Benin (located west of Nigeria), whereas lions from Yankari Game Reserve in
      central northeastern Nigeria grouped with the lion populations in Cameroon
      (located east of Nigeria). The finding that the two remaining lion populations in
      Nigeria have different phylogenetic origins is an important aspect to consider in
      future decisions regarding management and conservation of rapidly shrinking lion
      populations in West Africa. 

PMID- 25077019
TI  - Species-level view of population structure and gene flow for a critically
      endangered primate (Varecia variegata).
AB  - Lemurs are among the world's most threatened mammals. The critically endangered
      black-and-white ruffed lemur (Varecia variegata), in particular, has recently
      experienced rapid population declines due to habitat loss, ecological
      sensitivities to habitat degradation, and extensive human hunting pressure.
      Despite this, a recent study indicates that ruffed lemurs retain among the
      highest levels of genetic diversity for primates. Identifying how this diversity
      is apportioned and whether gene flow is maintained among remnant populations will
      help to diagnose and target conservation priorities. We sampled 209 individuals
      from 19 sites throughout the remaining V. variegata range. We used 10 polymorphic
      microsatellite loci and ~550 bp of mtDNA sequence data to evaluate genetic
      structure and population dynamics, including dispersal patterns and recent
      population declines. Bayesian cluster analyses identified two distinct genetic
      clusters, which optimally partitioned data into populations occurring on either
      side of the Mangoro River. Localities north of the Mangoro were characterized by
      greater genetic diversity, greater gene flow (lower genetic differentiation) and
      higher mtDNA haplotype and nucleotide diversity than those in the south. Despite
      this, genetic differentiation across all sites was high, as indicated by high
      average F ST (0.247) and PhiST (0.544), and followed a pattern of isolation-by
      distance. We use these results to suggest future conservation strategies that
      include an effort to maintain genetic diversity in the north and restore
      connectivity in the south. We also note the discordance between patterns of
      genetic differentiation and current subspecies taxonomy, and encourage a re
      evaluation of conservation management units moving forward. 

PMID- 25077020
TI  - Habitat heterogeneity drives the geographical distribution of beta diversity: the
      case of New Zealand stream invertebrates.
AB  - To define whether the beta diversity of stream invertebrate communities in New
      Zealand exhibits geographical variation unexplained by variation in gamma
      diversity and, if so, what mechanisms (productivity, habitat heterogeneity,
      dispersal limitation, disturbance) best explain the observed broad-scale beta
      diversity patterns. We sampled 120 streams across eight regions (stream
      catchments), spanning a north-south gradient of 12 degrees  of latitude, and
      calculated beta diversity (with both species richness and abundance data) for
      each region. We explored through a null model if beta diversity deviates from the
      expectation of stochastic assembly processes and whether the magnitude of the
      deviation varies geographically. We then performed multimodel inference analysis
      on the key environmental drivers of beta diversity, using Akaike's information
      criterion and model and predictor weights to select the best model(s) explaining
      beta diversity. Beta diversity was, unexpectedly, highest in the South Island.
      The null model analysis revealed that beta diversity was greater than expected by
      chance in all eight regions, but the magnitude of beta deviation was higher in
      the South Island, suggesting differences in environmental filtering and/or
      dispersal limitation between North and South Island. Habitat heterogeneity was
      the predominant driver of beta diversity of stream macroinvertebrates, with
      productivity having a secondary, and negative, contribution. This is one of the
      first studies accounting for stochastic effects while examining the ecological
      drivers of beta diversity. Our results suggest that local environmental
      heterogeneity may be the strongest determinant of beta diversity of stream
      invertebrates, more so than regional- or landscape-scale variables. 

PMID- 25077021
TI  - Operator bias in software-aided bat call identification.
AB  - Software-aided identification facilitates the handling of large sets of bat call
      recordings, which is particularly useful in extensive acoustic surveys with
      several collaborators. Species lists are generated by "objective" automated
      classification. Subsequent validation consists of removing any species not
      believed to be present. So far, very little is known about the identification
      bias introduced by individual validation of operators with varying degrees of
      experience. Effects on the quality of the resulting data may be considerable,
      especially for bat species that are difficult to identify acoustically. Using the
      batcorder system as an example, we compared validation results from 21 volunteer
      operators with 1-26 years of experience of working on bats. All of them validated
      identical recordings of bats from eastern Austria. The final outcomes were
      individual validated lists of plausible species. A questionnaire was used to
      enquire about individual experience and validation procedures. In the course of
      species validation, the operators reduced the software's estimate of species
      richness. The most experienced operators accepted the smallest percentage of
      species from the software's output and validated conservatively with low
      interoperator variability. Operators with intermediate experience accepted the
      largest percentage, with larger variability. Sixty-six percent of the operators,
      mainly with intermediate and low levels of experience, reintroduced species to
      their validated lists which had been identified by the automated classification,
      but were finally excluded from the unvalidated lists. These were, in many cases,
      rare and infrequently recorded species. The average dissimilarity of the
      validated species lists dropped with increasing numbers of recordings, tending
      toward a level of ~20%. Our results suggest that the operators succeeded in
      removing false positives and that they detected species that had been wrongly
      excluded during automated classification. Thus, manual validation of the
      software's unvalidated output is indispensable for reasonable results. However,
      although application seems easy, software-aided bat call identification requires
      an advanced level of operator experience. Identification bias during validation
      is a major issue, particularly in studies with more than one participant.
      Measures should be taken to standardize the validation process and harmonize the
      results of different operators. 

PMID- 25077023
TI  - Partitioning the sources of demographic variation reveals density-dependent nest
      predation in an island bird population.
AB  - Ecological factors often shape demography through multiple mechanisms, making it
      difficult to identify the sources of demographic variation. In particular,
      conspecific density can influence both the strength of competition and the
      predation rate, but density-dependent competition has received more attention,
      particularly among terrestrial vertebrates and in island populations. A better
      understanding of how both competition and predation contribute to density
      dependent variation in fecundity can be gained by partitioning the effects of
      density on offspring number from its effects on reproductive failure, while also
      evaluating how biotic and abiotic factors jointly shape demography. We examined
      the effects of population density and precipitation on fecundity, nest survival,
      and adult survival in an insular population of orange-crowned warblers
      (Oreothlypis celata) that breeds at high densities and exhibits a suite of traits
      suggesting strong intraspecific competition. Breeding density had a negative
      influence on fecundity, but it acted by increasing the probability of
      reproductive failure through nest predation, rather than through competition,
      which was predicted to reduce the number of offspring produced by successful
      individuals. Our results demonstrate that density-dependent nest predation can
      underlie the relationship between population density and fecundity even in a high
      density, insular population where intraspecific competition should be strong. 

PMID- 25077022
TI  - Diversity and evolution of the Wolbachia endosymbionts of Bemisia (Hemiptera:
      Aleyrodidae) whiteflies.
AB  - Wolbachia is the most prevalent symbiont described in arthropods to date.
      Wolbachia can manipulate host reproduction, provide nutrition to insect hosts and
      protect insect hosts from pathogenic viruses. So far, 13 supergroups of Wolbachia
      have been identified. The whitefly Bemisia tabaci is a complex containing more
      than 28 morphologically indistinguishable cryptic species. Some cryptic species
      of this complex are invasive. In this study, we report a comprehensive survey of
      Wolbachia in B. tabaci and its relative B. afer from 1658 insects representing 54
      populations across 13 provinces of China and one state of Australia. Based on the
      results of PCR or sequencing of the 16S rRNA gene, the overall rates of Wolbachia
      infection were 79.6% and 0.96% in the indigenous and invasive Bemisia whiteflies,
      respectively. We detected a new Wolbachia supergroup by sequencing five molecular
      marker genes including 16S rRNA, groEL, gltA, hcpA, and fbpA genes. Data showed
      that many protein-coding genes have limitations in detecting and classifying
      newly identified Wolbachia supergroups and thus raise a challenge to the known
      Wolbachia MLST standard analysis system. Besides, the other Wolbachia strains
      detected from whiteflies were clustered into supergroup B. Phylogenetic trees of
      whitefly mitochondrial cytochrome oxidase subunit I and Wolbachia multiple
      sequencing typing genes were not congruent. In addition, Wolbachia was also
      detected outside the special bacteriocytes in two cryptic species by fluorescence
      in situ hybridization, indicating the horizontal transmission of Wolbachia. Our
      results indicate that members of Wolbachia are far from well explored. 

PMID- 25077024
TI  - Timing matters: species-specific interactions between spawning time, substrate
      quality, and recruitment success in three salmonid species.
AB  - Substratum quality and oxygen supply to the interstitial zone are crucial for the
      reproductive success of salmonid fishes. At present, degradation of spawning
      grounds due to fine sediment deposition and colmation are recognized as main
      factors for reproductive failure. In addition, changes in water temperatures due
      to climate change, damming, and cooling water inlets are predicted to reduce
      hatching success. We tested the hypothesis that the biological effects of habitat
      degradation depend strongly on the species-specific spawning seasons and life
      history strategies (e.g., fall- vs. spring-spawners, migratory vs. resident
      species) and assessed temperature as an important species-specific factor for
      hatching success within river substratum. We studied the species-specific
      differences in their responses to such disturbances using egg-to-fry survival of
      Danube Salmon (Hucho hucho), resident brown trout (Salmo trutta fario), and
      migratory brown trout (Salmo trutta lacustris) as biological endpoint. The egg
      incubation and hatching success of the salmonids and their dependence on
      temperature and stream substratum quality were compared. Hatching rates of Danube
      salmon were lower than of brown trout, probably due to higher oxygen demands and
      increased interstitial respiration in spring. Increases in maximum water
      temperature reduced hatching rates of resident and migratory brown trout (both
      fall-spawners) but were positively correlated with hatching rates of Danube
      salmon (a spring-spawner). Significantly longer incubation periods of resident
      and migratory brown trout coincided with relatively low stream substratum quality
      at the end of the egg incubation. Danube salmon seem to avoid low oxygen
      concentrations in the hyporheic zone by faster egg development favored by higher
      water temperatures. Consequently, the prediction of effects of temperature
      changes and altered stream substratum properties on gravel-spawning fishes and
      biological communities should consider the observed species-specific variances in
      life-history strategies to increase conservation success. 

PMID- 25077025
TI  - The evolution of phenotypes and genetic parameters under preferential mating.
AB  - This article extends and adds more realism to Lande's analytical model for
      evolution under mate choice by using individual-based simulations in which
      females sample a finite number of males and the genetic architecture of the
      preference and preferred trait evolves. The simulations show that the equilibrium
      heritabilities of the preference and preferred trait and the genetic correlation
      between them (r G), depend critically on aspects of the mating system (the
      preference function, mode of mate choice, choosiness, and number of potential
      mates sampled), the presence or absence of natural selection on the preferred
      trait, and the initial genetic parameters. Under some parameter combinations,
      preferential mating increased the heritability of the preferred trait, providing
      a possible resolution for the lek paradox. The Kirkpatrick-Barton approximation
      for r G proved to be biased downward, but the realized genetic correlations were
      also low, generally <0.2. Such low values of r G indicate that coevolution of the
      preference and preferred trait is likely to be very slow and subject to
      significant stochastic variation. Lande's model accurately predicted the
      incidence of runaway selection in the simulations, except where preferences were
      relative and the preferred trait was subject to natural selection. In these
      cases, runaways were over- or underestimated, depending on the number of males
      sampled. We conclude that rapid coevolution of preferences and preferred traits
      is unlikely in natural populations, but that the parameter combinations most
      conducive to it are most likely to occur in lekking species. 

PMID- 25077026
TI  - Novel chemistry of invasive plants: exotic species have more unique metabolomic
      profiles than native congeners.
AB  - It is often assumed that exotic plants can become invasive when they possess
      novel secondary chemistry compared with native plants in the introduced range.
      Using untargeted metabolomic fingerprinting, we compared a broad range of
      metabolites of six successful exotic plant species and their native congeners of
      the family Asteraceae. Our results showed that plant chemistry is highly species
      specific and diverse among both exotic and native species. Nonetheless, the
      exotic species had on average a higher total number of metabolites and more
      species-unique metabolites compared with their native congeners. Herbivory led to
      an overall increase in metabolites in all plant species. Generalist herbivore
      performance was lower on most of the exotic species compared with the native
      species. We conclude that high chemical diversity and large phytochemical
      uniqueness of the exotic species could be indicative of biological invasion
      potential. 

PMID- 25077027
TI  - The future of the northeast Atlantic benthic flora in a high CO2 world.
AB  - Seaweed and seagrass communities in the northeast Atlantic have been profoundly
      impacted by humans, and the rate of change is accelerating rapidly due to runaway
      CO2 emissions and mounting pressures on coastlines associated with human
      population growth and increased consumption of finite resources. Here, we predict
      how rapid warming and acidification are likely to affect benthic flora and
      coastal ecosystems of the northeast Atlantic in this century, based on global
      evidence from the literature as interpreted by the collective knowledge of the
      authorship. We predict that warming will kill off kelp forests in the south and
      that ocean acidification will remove maerl habitat in the north. Seagrasses will
      proliferate, and associated epiphytes switch from calcified algae to diatoms and
      filamentous species. Invasive species will thrive in niches liberated by loss of
      native species and spread via exponential development of artificial marine
      structures. Combined impacts of seawater warming, ocean acidification, and
      increased storminess may replace structurally diverse seaweed canopies, with
      associated calcified and noncalcified flora, with simple habitats dominated by
      noncalcified, turf-forming seaweeds. 

PMID- 25077029
TI  - Increased blood-brain barrier permeability and alterations in perivascular
      astrocytes and pericytes induced by intracisternal glutaric acid.
AB  - BACKGROUND: Glutaric acid (GA) is a dicarboxylic acid that accumulates in
      millimolar concentrations in glutaric acidemia I (GA-I), an inherited
      neurometabolic childhood disease characterized by extensive neurodegeneration.
      Vascular dysfunction is a common and early pathological feature in GA-I, although
      the underlying mechanisms remain unknown. In the present study, we have used a
      previously-validated rat model of GA-I to determine the effect of GA on the blood
      brain barrier (BBB) and the neurovascular unit. METHODS: Newborn rat pups
      received a single injection of GA (1 MUmol/g) or vehicle into the cisterna magna.
      BBB permeability was analyzed at 14 and 30 days post injection (DPI) by assessing
      Evans blue (EB) and immunoglobulin G (IgG) extravasation. Blood vessels and
      microglia were labeled with tomato lectin. Characterization of EB positive cells
      was made by double labeling with antibodies to astrocyte and neuronal markers.
      Immunohistochemistry against aquaporin 4 (AQP4), beta receptor of the platelet
      derived growth factor (PDGFRbeta) and laminin was used to recognize astrocyte
      endfeet, pericytes and basal lamina. Zonula occludens 1 (ZO-1) and occludin
      striatal expression was assessed by Western blotting. RESULTS: Perinatal
      intracisternal GA administration caused an increased extravasation of free EB,
      but not of IgG, into the striatal parenchyma at 14 and 30 DPI. EB extravasated
      through the BBB was internalized exclusively into neurons. GA-injected animals
      did not show significant changes in the area of small blood vessels in the
      striatum, but at 30 DPI there was a significant decrease in AQP4, PDGFRbeta and
      laminin positive areas associated with small blood vessels. Occludin and ZO-1
      expression in the striatal tissue was unchanged in all conditions analyzed.
      CONCLUSIONS: The present study shows a previously-unknown effect of a perinatal
      administration of a single intracisternal GA injection on BBB permeability and on
      key components of the neurovascular unit. The results suggest BBB leakage is a
      pathogenic mechanism and a potential therapeutic target for patients with GA-I.

PMID- 25077030
TI  - Improving ethnocultural data to inform public health responses to communicable
      diseases in Australia.

PMID- 25077031
TI  - The ARM Network--a model for infectious disease surge response capacity in the
      Western Pacific Region.

PMID- 25077032
TI  - Response to a large rotavirus outbreak on South Tarawa, Kiribati, 2013.
AB  - INTRODUCTION: In July 2013, during annual independence celebrations in Kiribati,
      staff at Tungaru Central Hospital on South Tarawa reported an increase in
      children presenting with severe diarrhoea. This report describes the outbreak
      investigation, findings and response. METHOD: After notification of the outbreak,
      all health facilities on South Tarawa began reporting cases of acute diarrhoea
      and/or vomiting through the early warning syndromic surveillance system on a
      daily basis. Community awareness was raised and the public was encouraged to
      present to a health facility if ill with acute gastroenteritis. Specimens were
      collected and sent for laboratory testing. RESULTS: Between 10 and 24 July 2013,
      1118 cases of gastroenteritis were reported; 103 were hospitalized and six died.
      The median age of cases was one year (range: 0-68 years); 93.4% were aged less
      than five years. Rotavirus was identified in 81% of specimens tested. The
      outbreak response included enhanced surveillance, community education, clinical
      training and changes to in-hospital patient management for infection control.
      DISCUSSION: This outbreak was the largest diarrhoea outbreak in Kiribati in five
      years. Factors that may have contributed to the magnitude and severity of the
      outbreak included high household density, inadequate sanitation infrastructure
      and a mass gathering--all increasing the chance of transmission--as well as
      limited clinical response capacity. The current outbreak highlights the
      importance of clinical management to minimize severe dehydration and death.
      Rotavirus vaccination should be considered as an adjunct to other comprehensive
      enteric disease control measures as recommended by the World Health Organization.

PMID- 25077033
TI  - New South Wales annual vaccine-preventable disease report, 2012.
AB  - We aim to describe the epidemiology of selected vaccine-preventable diseases in
      New South Wales (NSW) for 2012. Data from the NSW Notifiable Conditions
      Information Management System were analysed by: local health district of
      residence, age, Aboriginality, vaccination status and organism, where available.
      Risk factor and vaccination status data were collected by public health units for
      cases following notification under the NSW Public Health Act 2010. The largest
      outbreak of measles since 1998 was reported in 2012. Pacific Islander and
      Aboriginal people were at higher risk as were infants less than 12 months of age.
      Notifications of invasive pneumococcal disease (IPD) in children less than five
      years declined; however, the overall number of notifications for IPD increased.
      Mumps case notifications were also elevated. There were no Haemophilus influenzae
      type b case notifications in children less than five years of age for the first
      time since the vaccine was introduced. Invasive meningococcal disease case
      notifications were at their lowest rates since case notification began in 1991.
      Case notification rates for other selected vaccine-preventable diseases remained
      stable. Vaccine-preventable disease control is continually strengthening in NSW
      with notable successes in invasive bacterial infections. However, strengthening
      measles immunization in Pacific Islander and Aboriginal communities remains
      essential to maintain measles elimination. 

PMID- 25077035
TI  - Ongoing increase in measles cases following importations, Japan, March 2014:
      times of challenge and opportunity.

PMID- 25077034
TI  - Implementing hospital-based surveillance for severe acute respiratory infections
      caused by influenza and other respiratory pathogens in New Zealand.
AB  - BACKGROUND: Recent experience with pandemic influenza A(H1N1)pdm09 highlighted
      the importance of global surveillance for severe respiratory disease to support
      pandemic preparedness and seasonal influenza control. Improved surveillance in
      the southern hemisphere is needed to provide critical data on influenza
      epidemiology, disease burden, circulating strains and effectiveness of influenza
      prevention and control measures. Hospital-based surveillance for severe acute
      respiratory infection (SARI) cases was established in New Zealand on 30 April
      2012. The aims were to measure incidence, prevalence, risk factors, clinical
      spectrum and outcomes for SARI and associated influenza and other respiratory
      pathogen cases as well as to understand influenza contribution to patients not
      meeting SARI case definition. METHODS/DESIGN: All inpatients with suspected
      respiratory infections who were admitted overnight to the study hospitals were
      screened daily. If a patient met the World Health Organization's SARI case
      definition, a respiratory specimen was tested for influenza and other respiratory
      pathogens. A case report form captured demographics, history of presenting
      illness, co-morbidities, disease course and outcome and risk factors. These data
      were supplemented from electronic clinical records and other linked data sources.
      DISCUSSION: Hospital-based SARI surveillance has been implemented and is fully
      functioning in New Zealand. Active, prospective, continuous, hospital-based SARI
      surveillance is useful in supporting pandemic preparedness for emerging influenza
      A(H7N9) virus infections and seasonal influenza prevention and control.

PMID- 25077036
TI  - Families or Unrelated: The Evolving Debate in Genetic Association Studies.
AB  - To help uncover the genetic determinants of complex disease, a scientist often
      designs an association study using either unrelated subjects or family members
      within pedigrees. But which of these two subject recruitment paradigms is
      preferable? This editorial addresses the debate over the relative merits of
      family- and population-based genetic association studies. We begin by briefly
      recounting the evolution of genetic epidemiology and the rich crossroads of
      statistics and genetics. We then detail the arguments for the two aforementioned
      paradigms in recent and current applications. Finally, we speculate on how the
      debate may progress with the emergence of next-generation sequencing
      technologies.

PMID- 25077038
TI  - Methylated Bone Morphogenetic Protein 3 (BMP3) Gene: Evaluation of Tumor
      Suppressor Function and Biomarker Potential in Biliary Cancer.
AB  - BACKGROUND: Although cholangiocarcinoma (CC) is an uncommon and highly lethal
      malignancy, early detection enables the application of potentially curative
      therapies and improves survival. Consequently, tools to improve the early
      diagnosis of CC are urgently needed. During a screen for genes epigenetically
      suppressed by methylation in CC that might serve as methylation markers for CC,
      we found that the BMP3 gene is methylated in CC cell lines, but the potential
      diagnostic value and the function of BMP3 in CC are unknown. METHODS: We aimed to
      quantitatively assess BMP3 methylation in resected CC tumor specimens using
      methylation specific PCR and evaluate the tumor suppressor role of BMP3 in
      biliary cancer cell lines in comparison to an immortalized normal cholangiocyte
      cell line. Expression of BMP3 was quantified by mRNA levels before and after
      treatment with 5-Aza-2'-deoxycytidine and trichostatin A. After transfection with
      a BMP3-containing plasmid, cell viability was measured using the
      bromodeoxyuridine incorporation assay and apoptosis quantified by caspase assay.
      RESULTS: In primary CC tumor tissue specimens significantly more methylated BMP3
      copies were found when compared to matched benign bile duct epithelium from the
      same patient, with high specificity. BMP3 expression was absent in cell lines
      with BMP3 methylation; this suppression of BMP3 expression was reversed by
      treatment with a DNA demethylating agent and histone de-acetylase inhibitor.
      Transfection of a BMP3-expressing construct into a BMP3-negative biliary cancer
      cell line restored BMP3 mRNA expression and reduced cell proliferation and cell
      viability while increasing the rate of apoptosis. CONCLUSION: These findings
      strongly support a tumor suppressor role for BMP3 in CC and suggest that BMP3
      methylation may be a new biomarker for early detection of CCs. of the peptidome
      are also involved.

PMID- 25077037
TI  - Pivotal Functions of Plasmacytoid Dendritic Cells in Systemic Autoimmune
      Pathogenesis.
AB  - Plasmacytoid dendritic cells (pDCs) were initially identified as the prominent
      natural type I interferon-producing cells during viral infection. Over the past
      decade, the aberrant production of interferon alpha/beta by pDCs in response to
      self-derived molecular entities has been critically implicated in the
      pathogenesis of systemic lupus erythematosus and recognized as a general feature
      underlying other autoimmune diseases. On top of imperative studies on human pDCs,
      the functional involvement and mechanism by which the pDC-interferon alpha/beta
      pathway facilitates the progression of autoimmunity have been unraveled recently
      from investigations with several experimental lupus models. This article reviews
      correlating information obtained from human in vitro characterization and murine
      in vivo studies and highlights the fundamental and multifaceted contribution of
      pDCs to the pathogenesis of systemic autoimmune manifestation.

PMID- 25077040
TI  - Transcriptional Regulation of Human NANOG by Alternate Promoters in Embryonic
      Stem Cells.
AB  - INTRODUCTION: The potential of pluripotent stem cells to be used for cell therapy
      depends on a comprehensive understanding of the molecular mechanisms underlying
      their unique ability to specify cells of all germ layers while undergoing
      unlimited self-renewal. Alternative splicing and alternate promoter selection
      contribute to this mechanism by increasing the number of transcripts generated
      from a single gene locus and thus enabling expression of novel protein variants
      which may differ in their biological role. The homeodomain-containing
      transcription factor NANOG plays a critical role in maintaining the pluripotency
      of Embryonic Stem Cells (ESC). Therefore, a thorough understanding of the
      transcriptional regulation of the NANOG locus in ESCs is necessary. METHODS:
      Regulatory footprints and transcription levels were identified for NANOG in human
      embryonic stem cells from data obtained using high-throughput sequencing
      methodologies. Quantitative real-time PCR following reverse transcription of RNA
      extracted human ESCs was used to validate the expression of transcripts from a
      region that extends upstream of the annotated NANOG transcriptional start.
      Promoter identification and characterization were performed using promoter
      reporter and electrophoretic mobility shift assays. RESULTS: Transcriptionally
      active chromatin marking and transcription factor binding site enrichment were
      observed at a region upstream of the known transcriptional start site of NANOG.
      Expression of novel transcripts from this transcriptionally active region
      confirmed the existence of NANOG alternative splicing in human ESCs. We
      identified an alternate NANOG promoter of significant strength at this upstream
      region. We also discovered that NANOG autoregulates its expression by binding to
      its proximal downstream promoter. CONCLUSION: Our study reveals novel transcript
      expression from NANOG in human ESCs, indicating that alternative splicing
      increases the diversity of transcripts originating from the NANOG locus and that
      these transcripts are expressed by an alternate promoter. Alternative splicing
      and alternate promoter usage collaborate to regulate NANOG, enabling its function
      in the maintenance of ESCs.

PMID- 25077039
TI  - Mammalian piRNAs: Biogenesis, function, and mysteries.
AB  - Piwi-interacting RNAs (piRNAs) are a distinct class of small non-coding RNAs
      specifically expressed in the germline of many species. They are most notably
      required for transposon silencing. Loss of piRNAs results in defects in germ cell
      development, and thus, infertility. Most studies of piRNAs have been done in
      Drosophila, but much progress has also been made on piRNAs in the germline of
      mammals and other species in the past few years. This review provides a summary
      of our current knowledge of the biogenesis and functions of piRNAs during mouse
      spermatogenesis and discusses challenges in the mammalian piRNA field.

PMID- 25077041
TI  - SVA retrotransposons as modulators of gene expression.
AB  - Endogenous mobile genetic elements can give rise to de novo germline or somatic
      mutations that can have dramatic consequences for genome regulation both local
      and possibly more globally based on the site of integration. However if we
      consider them as "normal genetic" components of the reference genome then they
      are likely to modify local chromatin structure which would have an effect on gene
      regulation irrelevant of their ability to further transpose. As such they can be
      treated as any other domain involved in a gene * environment interaction.
      Similarly their evolutionary appearance in the reference genome would supply a
      driver for species specific responses/traits. Our recent data would suggest the
      hominid specific subset of retrotransposons, SINE-VNTR-Alu (SVA), can function as
      transcriptional regulatory domains both in vivo and in vitro when analyzed in
      reporter gene constructs. Of particular interest in the SVA element, were the
      variable number tandem repeat (VNTR) domains which as their name suggests can be
      polymorphic. We and others have previously shown that VNTRs can be both
      differential regulators and biomarkers of disease based on the genotype of the
      repeat. Here, we provide an overview of why polymorphism in the SVA elements, in
      particular the VNTRs, could alter gene expression patterns that could be
      mechanistically associated with different traits in evolution or disease
      progression in humans.

PMID- 25077042
TI  - Gene Assembly from Chip-Synthesized Oligonucleotides.
AB  - De novo synthesis of long double-stranded DNA constructs has a myriad of
      applications in biology and biological engineering. However, its widespread
      adoption has been hindered by high costs. Cost can be significantly reduced by
      using oligonucleotides synthesized on high-density DNA chips. However, most
      methods for using off-chip DNA for gene synthesis have failed to scale due to the
      high error rates, low yields, and high chemical complexity of the chip
      synthesized oligonucleotides. We have recently demonstrated that some commercial
      DNA chip manufacturers have improved error rates, and that the issues of chemical
      complexity and low yields can be solved by using barcoded primers to accurately
      and efficiently amplify subpools of oligonucleotides. This article includes
      protocols for computationally designing the DNA chip, amplifying the
      oligonucleotide subpools, and assembling 500-800 basepair (bp) constructs.

PMID- 25077044
TI  - The effective use of graphs.

PMID- 25077043
TI  - Promoting Factors and Barriers to Participation in Early Phase Clinical Trials:
      Patients Perspectives.
AB  - BACKGROUND: Inclusion of minorities in clinical research is an essential step to
      develop novel cancer treatments, improve health care overall, understand
      potential differences in pharmacogenomics and address minorities'
      disproportionate cancer burden. However, Latinos and other minority groups
      continue to be critically underrepresented, particularly in early-phase clinical
      trials (EPCTs). The objective of the present study was to explore barriers and
      promoting factors influencing patients' decisions to enroll or not in early phase
      clinical trials (EPCTs) and identify areas for intervention to increase minority
      enrollment into clinical research. METHODS: An interviewer-administered survey
      was conducted with 100 cancer patients in the predominantly Latino region of
      South Texas. Exploratory factor analysis was conducted to identify underlying
      dimensions, and multiple logistic regression assessed significant factors that
      promote or deter patients enrollment to EPCTs. In addition, a separate subgroup
      mean analysis assessed differences by enrollment status and race/ethnicity.
      RESULTS: For one standard deviation increase in the importance given to the
      possibility of symptoms improvement, the predicted odds of refusing enrollment
      were 3.20 times greater (OR=3.20, 95% CI=1.06-9.71, p 0.040). Regarding barriers,
      among patients who considered fear/uncertainty of the new treatment a deterrent
      to enrollment, one standard deviation increase in agreement with these barriers
      was associated with a 3.60 increase (OR=3.60, 95% CI=1.30-9.97h, p 0.014) in the
      odds of not being enrolled in an EPCT. In contrast, non-enrolled patients were
      less likely (OR=0.14, 95% CI=0.05-0.44, p 0.001) to consider fatalistic beliefs
      as an important barrier. CONCLUSION: This study, one of the first to identify
      South Texas patients' barriers to enroll in EPCTs, highlights potential focal
      areas to increase participation of both minority and non-minority patients in
      clinical research. Culturally tailored interventions promoting patient-centered
      care and bilingual, culturally competent study teams could solve common barriers
      and enhance Latinos' likelihood of joining clinical trials. These interventions
      may simultaneously increase opportunities to involve patients and physicians in
      clinical trials, while ensuring the benefits of participation are equitably
      distributed to all patients.

PMID- 25077045
TI  - Ulnar shortening osteotomy for ulnar-sided wrist pain.
AB  - Background The purpose of ulnar shortening osteotomy is literally to shorten the
      ulna. It can tighten the triangular fibrocartilage complex (TFCC), ulnocarpal
      ligaments, and interosseous membrane. Nowadays, this method is used to treat
      ulnar-sided wrist pain, for which we have also started to use a treatment
      algorithm. The purpose of this study was to review the long-term and clinical
      results based on our algorithm. Materials and Methods We retrospectively reviewed
      30 patients with ulnocarpal impaction syndrome after a minimum follow-up of 5
      years (Group A) and then retrospectively evaluated 66 patients with recalcitrant
      ulnar wrist pain treated based on our algorithm (Group B). Description of
      Technique Ulnocarpal abutment was confirmed arthroscopically. The distal ulna was
      approached through a longitudinal incision between the extensor carpi ulnaris and
      flexor carpi ulnaris. We performed a transverse resection of the ulna fixed with
      a small locking compression plate. The contralateral side served as the reference
      for the length of shortening (mean, 2.4 mm; range, 1-5 mm). Disappearance of
      ulnar abutment was then confirmed again arthroscopically. Results (Group A) Most
      patients showed good long-term clinical results. About half of the patients
      showed a bony spur at the distal radioulnar joint (DRUJ), but the clinical
      results did not significantly correlate with presence of bony spurs. Radiological
      parameters wre not related to the presence of bony spurs. (Group B) Twenty-four
      of the 66 patients investigated prospectively underwent an ulnar shortening
      osteotomy, with all showing good clinical results at 18 months postoperatively.
      Conclusions Ulnar shortening osteotomy can change the load of the ulnar side of
      the wrist and appears useful for ulnar-sided wrist pain in the presence of ulnar
      impaction. Level of evidence IV. 

PMID- 25077046
TI  - The AO Ulnar Shortening Osteotomy System Indications and Surgical Technique.
AB  - Ulnar shortening osteotomy is an established and frequently performed surgical
      procedure in wrist surgery. The technical aspects of the procedure have continued
      to develop in recent years, with instruments and implants being developed
      specifically for this purpose. Ulnar shortening osteotomy is required for
      different clinical indications and situations. These varying indications demand
      different amounts of shortening, but all must be precise and accurate.
      Controversy exists as to how this can best be achieved in terms of the location
      for osteotomy, the surgical approach and geometry of the osteotomy, as well as
      which implant to use to provide optimal stability. The goal of all techniques
      (besides successfully resolving the underlying problem) is to achieve reliable
      and rapid bone union without compromising early functional rehabilitation and
      also to avoid hardware complications. The AO Hand Expert Group has developed a
      specialized instrumentation system with dedicated and specifically designed
      implants to ensure exact and accurate cutting with precise and rigid
      stabilization of the ulna. The matched drill guides and double-blade saws allow
      accurate completion of the planned amount of shortening together with precise
      coaptation of the osteotomy fragments. The specific ulnar osteotomy LCP (locking
      compression plate) combines maximum stability with minimum bulk and soft tissue
      irritation. The features of the implant, its surgical technique, and early
      results are described. 

PMID- 25077047
TI  - Biomechanical Test of Three Methods to Treat Thumb CMC Arthritis.
AB  - Background Basilar thumb arthritis, or first carpometacarpal arthritis, is a
      common condition, predominantly affecting women. Surgical treatment of this
      condition is highly varied. One common method consists of trapezium excision and
      a concomitant procedure for treatment of the "floating" thumb metacarpal. That
      procedures vary suggests that no method has an "outcome" advantage over another.
      However, the frequency of side effects is higher in more complex procedures.
      Question/Purposes We speculated that in vitro testing might identify a potential
      outcome difference that has been difficult to measure in vivo. Since the more
      complex procedure to treat this condition has a higher frequency of clinical side
      effects, we hoped to determine its functional value compared with less complex
      procedures. Methods A two-degrees-of-freedom biomechanical cadaver study examined
      simulated pinch strength and metacarpal subsidence during pinch. Three methods
      were compared with each other and against the normal pretreatment state:
      trapezial excision alone; trapezial excision and suture suspensionplasty (TESS);
      and trapezial excision followed by a ligament reconstruction using one-half of
      the flexor carpi radialis and tendon interposition (LRTI). Results After TESS,
      the loaded mean height of the arthroplasty space was 1.20 cm. This was
      statistically less than the pretreatment height of 1.50 cm (P < 0.05). However,
      the height maintained after LRTI (1.00 cm) was also statistically less than
      pretreatment state (P < 0.05) and less than TESS (P < 0.05). Trapezial excision
      alone was least successful at maintaining height. In contrast, the mean key pinch
      measured after treatment could not be predicted by treatment employed.
      Conclusions In summary, the tested technique of TESS appears to be
      biomechanically sound as related to maintenance of first metacarpal height. In in
      vitro testing it is superior to excision alone and at least equal to the ligament
      reconstruction method tested. Analysis of our data shows that 96% of the overall
      height (distance) maintained post excision is explained by surgical state.
      Clinical Relevance Trapezial height is preserved using support schemes in a
      laboratory setting. In the in vivo postsurgical state, clinical intrinsic muscle
      function may be superior when support is used compared with trapeziectomy alone. 

PMID- 25077048
TI  - The clinical outcome after extra-articular colles fractures with simultaneous
      moderate scapholunate dissociation.
AB  - Background An increased scapholunate gap is sometimes seen in patients with a
      distal radial fracture. The question remains as to whether this represents a
      scapholunate ligament injury that requires treatment. Questions/purposes We
      wished to examine the natural history of an increased scapholunate gap in
      patients following an extra-articular distal radial fracture. Patients and
      Methods We reviewed 260 patients who had sustained a distal radial fracture at a
      mean of 6.2 (2.7-11.9) years previously and identified 12 extra-articular
      fractures with an increased gap between the lunate and scaphoid. The mean
      scapholunate gap was 2.6 (2.1-3.4) mm, and the mean scapholunate angle 62 degrees
      (39 degrees -90 degrees ). Controls were found among the remaining patients with
      extra-articular fractures. Selection criteria were same sex, age at fracture
      within 5 years, time between injury and review within 2 years, ulnar variance
      within 2 mm, and dorsal angulation within 5 degrees  of index patient. When more
      than one control fulfilled the criteria for an index patient, their values were
      averaged. In total there were 54 controls for the 12 index patients. Results The
      mean difference between index patients and controls in wrist range of motion was
      4%, in grip strength 5%, in visual analog scale (VAS) for pain 1 (on a scale from
      1 to 100), in Quick-DASH (Disability of the Arm, Shoulder, and Hand) score 5, and
      in PRWE score 1. The study was calculated to have the power to detect a
      difference in Quick-DASH scores and in Patient-Rated Wrist Evaluation (PRWE)
      scores of 14. Conclusions We conclude that at a mean follow up of 6.2 years
      following an extra-articular distal radial fracture, no surgical treatment is
      usually needed with a scapholunate gap of between 2.1-3.4 mm. Level of Evidence
      III, Case control study. 

PMID- 25077049
TI  - The use of navigation forces for assessment of wrist arthroscopy skills level.
AB  - Purpose To provide an efficient learning process, feedback on performance is
      crucial. In skills laboratories, it is possible to measure the skills and
      progression of skills of the trainees objectively. This requires metrics that
      represent the learning curve of the trainee, which were investigated for wrist
      arthroscopy. The research questions were: What are the forces used by novices
      during wrist arthroscopy?What aspects of these navigation forces are
      discriminative for the wrist arthroscopy skills level?Methods A cadaver wrist was
      mounted in a custom-made distraction device mounted in front of a force platform
      (ForceTrap). Eleven novices were invited to perform two tasks on the wrist:
      Insertion of the scope through the 3-4 portal and the hook through the 6R portal,
      and visualization of the hook in the center of the imageNavigation through the
      wrist from radial to ulnar with probing and visualization of five predefined
      landmarksThe second task was repeated 10 times. The absolute force (F abs) and
      the direction of force were measured. The angle alpha is defined in the vertical
      plane, and the angle beta in the horizontal plane. Results The median F abs used
      by novices remained below the force threshold as defined from the expert data
      (7.3 N). However, the direction of the applied forces by novices in both planes
      was not consistent with expert data and showed a wider range. Also, there was no
      improvement after more trials. Conclusion Our study suggests by the absence of a
      learning curve for the novices and a significant difference between novices and
      experts that novices can benefit from feedback on the magnitude and direction of
      forces to improve their performance. 

PMID- 25077050
TI  - Rupture of the flexor digitorum superficialis at the musculotendinous junction
      due to a forearm fracture: a case report.
AB  - We present a case of a closed distal-third forearm fracture, in which the flexor
      digitorum superficialis was found ruptured at its musculotendinous junction. We
      diagnosed the ruptured tendon during the exploration of the ulnar nerve for
      observed preoperative palsy. Although there are numerous reports about avulsions
      at the bony insertions, there are very few about avulsion at the musculotendinous
      junction in the literature. This consideration leads to the conclusion that this
      kind of rupture may be more frequent than recognized. 

PMID- 25077051
TI  - Reply to Letter to the Editor on: Augmented Reality-Based Navigation System for
      Wrist Arthroscopy: Feasability (J Wrist Surg 2013;2(4):294-298).

PMID- 25077052
TI  - Response to the Letter to the Editor on: Dorsal Capsuloplasty for Dorsal
      Instability of the Distal Ulna (J Wrist Surg 2013;2(2):168-175).

PMID- 25077053
TI  - High phosphoserine in sepsis: panel of clinical and plasma amino acid
      correlations.
AB  - The determination of plasma phosphoserine concentration in sepsis is uncommon,
      and the clinical and metabolic correlations of abnormally high phosphoserine are
      basically unknown. We analyzed 430 determinations of phosphoserine, other amino
      acid (AA) levels and ancillary variables obtained in 18 septic patients, in order
      to assess the biochemical and clinical correlations of changes in phosphoserine.
      Phosphoserine ranged between 5 and 55 micromol/L (n.v. < 12). Increasing
      phosphoserine was associated with higher severity of illness and death, and its
      best AA correlates were increasing cystathionine, 3-methylhistidine, histidine,
      hydroxyproline and tyrosine (r > 0.65, p < 0.001 for all). High phosphoserine
      seemed to cumulatively reflect kidney and liver dysfunction and enhanced
      proteolysis. As a collateral finding, 3-methylhistidine (a best correlate of
      phosphoserine) was also inversely related to nutritional AA dose (p < 0.001).
      These data suggest that in septic patients the determination of plasma
      phosphoserine may provide useful information on severity of septic illness and
      prognosis. The observed correlations also indirectly evidenced an impact of
      nutritional AA dose in moderating proteolysis. 

PMID- 25077054
TI  - Oscillation theorems for second order nonlinear forced differential equations.
AB  - In this paper, a class of second order forced nonlinear differential equation is
      considered and several new oscillation theorems are obtained. Our results
      generalize and improve those known ones in the literature. 

PMID- 25077055
TI  - A system of nonlinear set valued variational inclusions.
AB  - ABSTRACT: In this paper, we studied the existence theorems and techniques for
      finding the solutions of a system of nonlinear set valued variational inclusions
      in Hilbert spaces. To overcome the difficulties, due to the presence of a proper
      convex lower semicontinuous function phi and a mapping g which appeared in the
      considered problems, we have used the resolvent operator technique to suggest an
      iterative algorithm to compute approximate solutions of the system of nonlinear
      set valued variational inclusions. The convergence of the iterative sequences
      generated by algorithm is also proved. AMS MATHEMATICS SUBJECT CLASSIFICATION:
      49J40; 47H06.

PMID- 25077056
TI  - Development of youth friendly family medicine services in Bosnia and Herzegovina:
      protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: Young people face many barriers in accessing health services that are
      responsive to their needs. The World Health Organization has led a call to
      develop services that address these barriers, i.e. youth-friendly health
      services. Addressing the needs of young people is one of the priorities of
      Foundation fami, an organisation working in collaboration with the Swiss Federal
      Department of Development and Cooperation and Geneva University Hospitals to
      develop quality family medicine services in Bosnia and Herzegovina. This paper
      describes the design of a trial to assess the effectiveness of a multifaceted
      intervention involving family medicine teams (primary care doctors and nurses) to
      improve the youth-friendliness of family medicine services in Bosnia and
      Herzegovina. METHODS/DESIGN: This is a stratified cluster randomised trial with a
      repeated cross-sectional design involving 59 health services in 10 municipalities
      of the canton of Zenica in Bosnia and Herzegovina. Municipalities were the unit
      of randomisation: five municipalities were randomised to the intervention arm and
      five to a wait-list control arm. Family medicine teams in the intervention arm
      were invited to participate in an interactive training program about youth
      friendly service principles and change processes within their service. The
      primary outcome was the youth-friendliness of the primary care service measured
      using the YFHS-WHO + questionnaire, a validated tool which young people aged 15
      to 24 years complete following a family medicine consultation. A total of 600
      young people aged 15 to 24 years were invited to participate and complete the
      YFHS-WHO + questionnaire: 300 (30 per municipality) at baseline, and 300 at
      follow-up, three to five months after the training program. DISCUSSION: The
      results of this trial should provide much awaited evidence about the development
      of youth-friendly primary care services and inform their further development both
      in Bosnia and Herzegovina and worldwide. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry_ ACTRN12610000142033.

PMID- 25077057
TI  - Raw agro-industrial orange peel waste as a low cost effective inducer for
      alkaline polygalacturonase production from Bacillus licheniformis SHG10.
AB  - The current study underlines biotechnological valorization of the accumulated and
      the non-efficiently utilized agro-industrial orange peel waste to produce
      polygalacturonase (PGase), an industrially important enzyme with augmented
      demands in enzymes markets, from Bacillus licheniformis SHG10. Sequential
      statistical optimization of PGase production was performed through one variable
      at a time (OVAT) approach, Plackett-Burman (PB) and response surface methodology
      (RSM). The impact of introduction of six raw agro-industrial wastes (orange,
      lemon, banana, pomegranate, artichoke peel wastes and wheat bran) and other
      synthetic carbon sources separately into the fermentation broth on PGase
      productivity was studied through OVAT approach. Orange peel waste as sole raw
      carbon source in basal medium proved to be the best PGase inducer. It promoted
      PGase productivity with relative specific activity of 166% comparable with the
      effect imposed by synthetic citrus pectin as a reference inducer. Three key
      determinants (orange peel waste, pH of the production medium and incubation
      temperature) had RSM optimal levels of 1.76% (w/v), 8.0 and 37.8 degrees C,
      respectively along with maximal PGase level (2.69 MUg galacturonic acid. min(-1).
      mg(-1)) within 48 hrs. Moreover, SHG10 PGase exhibited activity over a wide range
      of pH (3-11) and an optimal activity at 50 degrees C. Data greatly encourage
      pilot scale PGase production from B. licheniformis SHG10. 

PMID- 25077059
TI  - Utilizing the Intercultural Development Inventory(r) to develop intercultural
      competence.
AB  - PURPOSE: Health care professional education programs in the United States have
      been charged to devise strategies to increase the racial and ethnic diversity of
      the workforce (Health Resources and Services Administration, Nursing Workforce
      Diversity (NWD) http://bhpr.hrsa.gov/nursing/grants/nwd.html, 2014). The purpose
      of this charge is to develop a healthcare workforce that can better provide
      culturally relevant care to meet the needs of diverse communities. The purpose of
      this study was to assess the cultural competency of students, faculty, and staff
      from a small Midwest-university college of nursing. METHODS: This study was part
      of a larger interventional study to enhance the cultural development of the
      College of Nursing faculty, staff, and students. The sample for this study
      included 314 participants (students, faculty, and staff) in phase one of the
      parent study. Phase one included the initial administration of the Intercultural
      Development Inventory (IDI(r)) over a two year period with analysis of the pre
      test results. Phase two includes the implementation of cultural development
      interventions with a post-test IDI(r) survey and is currently in process.
      RESULTS: IDI(r) aggregate results were similar for students and faculty/staff in
      that most participants scored at the Minimization level according to the IDI(r).
      Ninety-eight percent of student participants overestimated their level of
      cultural competency. Minority students had higher cultural competency scores in
      terms of developmental orientation (M = 98.85, SD = 14.21) compared to non
      minority students (M = 94.46, SD = 14.96). CONCLUSIONS: Overall, the IDI(r) was a
      valuable self-reflection tool to assess cultural development. At the individual
      level, it has allowed for self-reflection and awareness to the reality of
      cultural development, attitudes, and values. At an institutional level, the
      aggregate results provided a framework for the examination of department
      policies, procedures, and curriculum design with the ultimate goal of graduating
      a more culturally competent nursing workforce to serve the greater community.

PMID- 25077058
TI  - The epidemiology, risk factors, and impact on hospital mortality of status
      epilepticus after subdural hematoma in the United States.
AB  - INTRODUCTION: Subdural hematoma (SDH) is a well described risk factor in the
      development of Status Epilepticus (SE), however the epidemiology of SE after SDH
      is unknown. In this study, we sought to determine the epidemiology of SE, the
      prevalence of risk factors, and impact on hospital mortality using a large
      administrative dataset. METHODS: Data was derived from the Nationwide Inpatient
      Sample from 1988 through 2011. We queried the NIS database for patients older
      than 18 years, with a diagnosis of SDH and SE. Diagnoses were defined by ICD 9 CM
      codes 432.1, 852.2, 852.3 and 345.3 for SE. Adjusted incidence rates of admission
      and prevalence proportions were calculated. Multivariate logistic models were
      then fitted to assess for the impact of status epilepticus on hospital mortality.
      RESULTS: Over the 23-year period, we identified more than 1,583,255 admissions
      with a diagnosis of SDH. The prevalence of SE in this cohort was 0.5% (7,421
      admissions). The population adjusted incidence rate of admissions of SDH
      increased from 13/100,000 in 1988 to 38/100,000 in 2011. The prevalence of SE in
      SDH, increased from 0.5% in 1988 to 0.7% in 2011. In hospital mortality of
      patients with SDH and without SE decreased from 17.9% to 10.3% while in hospital
      mortality of patients with SDH and SE did not statistically change. Mortality
      increased over the same period (2.3/100,000 in 1988 to 3.9/100.000 in 2011) and
      the diagnosis of SE increased mortality in this cohort (OR 2.17, p < 0.0001). The
      risk of SE remained stable throughout the study period, but was higher among
      older patients, blacks, and in those with respiratory, metabolic, hematological,
      and renal system dysfunction. CONCLUSION: Our study demonstrates that the
      incidence of admissions of SDH is increasing in the United States. Despite a
      decline in the overall SDH related mortality, SE increased the risk of in
      hospital death in patients with a primary diagnosis of SDH.

PMID- 25077060
TI  - Cloning, expression and purification of functionally active human angiopoietin
      like protein 2.
AB  - Angiopoietin-like protein 2 (Angptl2) is a secreted glycoprotein that has been
      implicated in angiogenesis, inflammation and atherosclerosis as well as enhancing
      the survival of human hematopoietic stem cells. Glycosylation of Angptl2 is
      required for biological activity and studies of angiopoietin-like protein 2 have
      been hindered by the lack of a source for the mature form of this protein. We
      describe a system that permits purification of the glycosylated form of human
      Angptl2 from conditioned media of stably transfected HEK 293 cells. To facilitate
      purification while retaining the integrity of Angptl2's endogenous N-terminal
      secretion signal peptide, GST was fused downstream of the Angptl2 coding
      sequence. Secreted Angptl2-GST was purified using a one-step glutathione-affinity
      purification scheme. The purity and identity of the resulting protein were
      confirmed by SDS-PAGE, immunoblotting, and mass spectrometry. N-Glycosidase
      treatment reduced the apparent molecular mass of Angptl2-GST on SDS-PAGE,
      confirming its glycosylation state. Purified human Angptl2-GST stimulated both
      HUVEC migration and microtubule formation in vitro. The yield of Angptl2-GST
      obtained was in quantities suitable for multiple applications including
      functional in vitro and in vivo assays. 

PMID- 25077061
TI  - Determination of traces of molybdenum and lead in foods by x-ray fluorescence
      spectrometry.
AB  - An Energy Dispersive X-ray Fluorescence (EDXRF) method using X-ray emitting
      isotopes in combination with pre-concentration by carbonization was developed to
      determine the levels of Mo and Pb accumulated in foods. The samples were
      carbonized at temperatures range of 150-400 degrees C for 15 min to 2 h for
      powdering. The powder was then quickly formed into a pellet for EDXRF analysis.
      This analytical method (detection limit, 0.08 mg/kg) was used to determine levels
      of Mo and Pb in several kinds of foods from the local kitchen markets. The
      analytical results indicated that higher concentration of Mo (2.51 +/- 0.09
      mg/kg) and Pb (0.62 +/- 0.13 mg/kg) was present in pulse. The maximum lead
      concentration is also found in pulses with the mean value of, which is far below
      the maximum permissible limit (ASP, pp 235, 1980) of Pb in food (1-5 mg/kg). The
      possibility of determination of traces of Mo and Pb in foods by x-ray
      fluorescence after carbonization is evaluated by comparative studies of standard
      reference materials. The method enables fast and direct analysis to be carried
      out without lengthy sample pretreatment and thereby minimizing sample
      contamination on a routine basis for food monitoring. No loss (<5%) of Mo and Pb
      is observed and a significant matrix reduction is achieved. Our findings
      highlighted that this method could be used for monitoring the levels of heavy
      metals (like Mo and Pb) accumulation in foods within short time and people can
      avoid health risk due to toxic effect of food. 

PMID- 25077062
TI  - Neuroblastoma presenting like a Wilms' tumor with thrombus in inferior vena cava
      and pulmonary metastases: a case series.
AB  - Neuroblastomas and Wilms' tumors are frequent pediatric solid tumors. The first
      is frequently detected in the adrenal gland and the second develops in the
      kidneys. The extension through the vena cava and the lung metastases are frequent
      in Wilms' tumors and are rarely seen in neuroblastoma. We present the cases of
      three children with abdominal tumors with thrombus in the inferior vena cava and
      pulmonary metastases demonstrating a stage 4 neuroblastoma. The three male
      patients were between 23 to 48 months old. They presented an abdominal mass, near
      the superior pole of the kidney. Thrombus of the vena cava was showed on imaging
      studies in all cases and pulmonary metastases were always found. Catecholamine
      metabolites were present in the first case and negative in the two others. Two
      out of three patients had a radical nephrectomy. The pathological analysis always
      found a poorly differentiated or undifferentiated neuroblastoma without MYCN
      amplification and confirmed the vein tumoral thrombus in the second case. The
      evolution of the first two patients was unfavorable and the third is alive.
      Invasion of the inferior vena cava and pulmonary metastases in children with
      neuroblastoma is uncommon and can modify the surgical management. 

PMID- 25077064
TI  - A thick placenta: a predictor of adverse pregnancy outcomes.
AB  - PURPOSE: The aim of this study is to evaluate the efficacy of an ultrasonographic
      measurement of placental thickness and the correlation of a thick placenta with
      adverse perinatal outcome. METHODS: Placental thickness was measured in single
      gravidas, 16 to 40 weeks of gestation, between 2005 and 2009. Placentas were
      considered to be thick if their measured thickness were above the 95th percentile
      for gestational age. RESULTS: The incidence of thick placentas was 4.3%
      (138/3,183). Perinatal morbidity and neonatal conditions were worse in cases with
      thick placenta rather than without thick placenta. CONCLUSIONS: Ultrasonographic
      measurement of placental thickness is a simple method to estimate placental size.
      Thick placenta may be a useful predictor of adverse pregnancy outcomes.

PMID- 25077063
TI  - Changes in ovarian function in premenopausal women with breast cancer undergoing
      adjuvant TC (docetaxel and cyclophosphamide) chemotherapy during a brief period
      of amenorrhea around the last chemotherapy cycle.
AB  - PURPOSE: Docetaxel, a chemotherapeutic agent, induces high rates of transient
      chemotherapy-induced amenorrhea (CIA) when used as adjuvant chemotherapy for
      premenopausal women with breast cancer. Clinical laboratory data to assess the
      hormonal environment implicated in inducing transient CIA was assessed. METHODS:
      An observational study was conducted in 35 premenopausal women with hormone
      responsive breast cancer who were receiving adjuvant docetaxel/cyclophosphamide
      (TC) chemotherapy. Serum estradiol and follicular stimulating hormone (FSH)
      levels were measured at one (n = 6) or two (n = 29) time point(s) around the
      completion of chemotherapy. RESULTS: As early as week 6 after the start of
      chemotherapy, just before the third TC cycle, serum estradiol levels were
      invariably suppressed (median of 5.5 pg/ml, n = 15, range <5-18.7 pg/ml) and FSH
      levels increased (median of 63.9 mIU/ml, range 24.5-127.4 mIU/ml), indicative of
      ovarian suppression to the menopausal levels. Subsequently, at 9 and 12 weeks,
      serum estradiol levels were suppressed to a median of 6.6 pg/ml (n = 49, range <5
      17.3 pg/ml), while FSH levels were high (median of 66.8 mIU/ml, range 29.2-134.5
      mIU/ml). There was a significant Spearman's correlation (rho = 0.95, n = 29, p <
      0.01) of high serum FSH levels (24.5-134.5 mIU/ml) between two time points of
      repeated measurements in 29 patients. TC chemotherapy induced rapid ovarian
      suppression with the formation of a high and stable plateau in serum FSH levels
      from week 6 to week 12. CONCLUSIONS: Recovery from transient CIA post-therapy may
      be partially attributed to high, stable FSH levels that occurred as early as
      after completion of the second TC chemotherapy cycle.

PMID- 25077065
TI  - High antioxidant and DNA protection activities of N-acetylglucosamine (GlcNAc)
      and chitobiose produced by exolytic chitinase from Bacillus cereus EW5.
AB  - Chitin-degrading bacterial strains were screened and tested for their ability to
      degrade shrimp-shell waste (SSW). Among the potential strains, B. cereus EW5
      exhibited the highest chitin-degrading ability compared with other strains and
      produced 24 mg of reducing sugar per gram of dry SSW after 4 days of incubation.
      A TLC analysis of SSW biodegradation revealed that the chitosaccharides produced
      in the culture supernatant were mainly N-acetylglucosamine (GlcNAc) and
      chitobiose due to the isolate's exolytic chitinase activity. The culture
      supernatant exhibited a high degree of antioxidant activity, as indicated by 83%
      DPPH, 99.6% ABTS, 51% hydroxyl radical scavenging activity and 0.34 reducing
      power. The formation of GlcNAc and chitobiose during biodegradation of SSW is
      considered to be the major contributor to the antioxidant activity. The EW5
      culture supernatant also displayed inhibition of DNA damage, enhancing the
      reutilization value of SSW. This report presents the first description of
      fermented production of GlcNAc and DNA protective activity of culture supernatant
      from SSW by B. cereus. 

PMID- 25077066
TI  - Hormone dependent metastatic salivary gland carcinoma: a case report.
AB  - Adenocarcinoma of the salivary gland is a histology subtype of salivary gland
      carcinoma (SGC). Salivary gland carcinomas are rare tumors accounting for less
      than 5% of all cancers of the head and neck. Consequently, clinical data for
      systemic treatment including targeted treatment in metastatic SGC is limited and
      supported mainly by sporadic cases, retrospective reports, and early phase trials
      with a limited number of patients. We present a case of a patient who suffered
      from metastatic SGC, in whom novel molecular testing that uses
      immunohistochemical analysis and DNA microarray implied that the tumor would
      respond to anti-androgen treatment. The patient was given bicalutamide and
      achieved complete objective response. 

PMID- 25077067
TI  - Properties of GPS noise at Japan islands before and after Tohoku mega-earthquake.
AB  - The field of 3-components GPS signals is analyzed for the network of 1203
      stations at the Japanese islands from January 30 up to March 26, 2011. This time
      interval includes just over 40 days of observation before the Tohoku mega
      earthquake on March 11, 2011 (M = 9.0) and nearly 16 days of observation
      following this event. The signals from each station are three-component time
      series with time step 30 minutes. We study the statistical properties of the
      random fluctuations of GPS signals before and after the seismic catastrophe after
      transition to increments. The values of wavelet-based spectral index for GPS
      noise components for each station were estimated separately for pieces of records
      before and after seismic event. The maps of the noise spectral index are
      constructed as the values for grid size of 50 * 50 nodes covering the region
      under study, based on information from 10 stations closest to each node. These
      maps clearly extract the region of future seismic catastrophe by relatively high
      noise spectral index. The using of principal components method distinguished this
      spatial anomaly more explicitly. These results support the hypothesis that
      statistical properties of random fluctuations of geophysical fields carry
      important information about earthquake preparation. 

PMID- 25077068
TI  - Identification of novel glycosyl hydrolases with cellulolytic activity against
      crystalline cellulose from metagenomic libraries constructed from bacterial
      enrichment cultures.
AB  - To obtain cellulases that are capable of degrading crystalline cellulose and
      cedar wood, metagenomic libraries were constructed from raw soil sample which was
      covered to pile of cedar wood sawdust or from its enrichment cultures. The
      efficiency of screening of metagenomic library was improved more than 3 times by
      repeating enrichment cultivation using crystalline cellulose as a carbon source,
      compared with the library constructed from raw soil. Four cellulase genes were
      obtained from the metagenomic libraries that were constructed from the total
      genome extracted from an enrichment culture that used crystalline cellulose as a
      carbon source. A cellulase gene and a xylanase gene were obtained from the
      enrichment culture that used unbleached kraft pulp as a carbon source. The
      culture supernatants of Escherichia coli expressing three clones that were
      derived from the enrichment culture that used crystalline cellulose showed
      activity against crystalline cellulose. In addition, these three enzyme solutions
      generated a reducing sugar from cedar wood powder. From these results, the
      construction of a metagenomic library from cultures that were repetition enriched
      using crystalline cellulose demonstrated that this technique is a powerful tool
      for obtaining cellulases that have activity toward crystalline cellulose. 

PMID- 25077069
TI  - Sequential administration of carbon nanotubes and near-infrared radiation for the
      treatment of gliomas.
AB  - The objective was to use carbon nanotubes (CNT) coupled with near-infrared
      radiation (NIR) to induce hyperthermia as a novel non-ionizing radiation
      treatment for primary brain tumors, glioblastoma multiforme (GBM). In this study,
      we report the therapeutic potential of hyperthermia-induced thermal ablation
      using the sequential administration of carbon nanotubes (CNT) and NIR. In vitro
      studies were performed using glioma tumor cell lines (U251, U87, LN229, T98G).
      Glioma cells were incubated with CNTs for 24 h followed by exposure to NIR for 10
      min. Glioma cells preferentially internalized CNTs, which upon NIR exposure,
      generated heat, causing necrotic cell death. There were minimal effects to normal
      cells, which correlate to their minimal uptake of CNTs. Furthermore, this
      protocol caused cell death to glioma cancer stem cells, and drug-resistant as
      well as drug-sensitive glioma cells. This sequential hyperthermia therapy was
      effective in vivo in the rodent tumor model resulting in tumor shrinkage and no
      recurrence after only one treatment. In conclusion, this sequence of selective
      CNT administration followed by NIR activation provides a new approach to the
      treatment of glioma, particularly drug-resistant gliomas. 

PMID- 25077070
TI  - Non-Small Cell Lung Carcinoma Biomarker Testing: The Pathologist's Perspective.
AB  - Biomarker testing has become standard of care for patients diagnosed with non
      small cell lung carcinoma (NSCLC). Although, it can be successfully performed in
      circulating tumor cells, at present, the vast majority of investigations are
      carried out using direct tumor sampling, either through aspiration methods, which
      render most often isolated cells, or tissue sampling, that could range from
      minute biopsies to large resections. Consequently, pathologists play a central
      role in this process. Recent evidence suggests that refining NSCLC diagnosis
      might be clinically significant, particularly in cases of lung adenocarcinomas
      (ADC), which in turn, has prompted a new proposal for the histologic
      classification of such pulmonary neoplasms. These changes, in conjunction with
      the mandatory incorporation of biomarker testing in routine NSCLC tissue
      processing, have directly affected the pathologist's role in lung cancer work-up.
      This new role pathologists must play is complex and demanding, and requires a
      close interaction with surgeons, oncologists, radiologists, and molecular
      pathologists. Pathologists often find themselves as the central figure in the
      coordination of a process, that involves assuring that the tumor samples are
      properly fixed, but without disruption of the DNA structure, obtaining the proper
      diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of
      tumor samples selected for biomarker testing, which includes assessment of the
      proportion of tumor to normal tissues, as well as cell viability, and assuring
      that this entire process happens in a timely fashion. Therefore, it is part of
      the pathologist's responsibilities to assure that the samples received in their
      laboratories, be processed in a manner that allows for optimal biomarker testing.
      This article goal is to discuss the essential role pathologists must play in
      NSCLC biomarker testing, as well as to provide a summarized review of the main
      NSCLC biomarkers of clinical interest. 

PMID- 25077071
TI  - Carbohydrate-mediated modulation of NK cell receptor function: structural and
      functional influences of heparan sulfate moieties expressed on NK cell surface.

PMID- 25077073
TI  - Historical and contemporary hypotheses on the development of oral diseases: are
      we there yet?
AB  - Dental plaque is an oral biofilm that much like the rest of our microbiome has a
      role in health and disease. Specifically, it is the cause of very common oral
      diseases such as caries, gingivitis, and periodontitis. The ideas about oral
      disease development have evolved over time. In the nineteenth century, scientists
      could not identify bacteria related to disease due to the lack of technology.
      This led to the "Non-Specific Plaque Hypothesis" or the idea that the
      accumulation of dental plaque was responsible for oral disease without
      discriminating between the levels of virulence of bacteria. In the twentieth
      century this idea evolved with the techniques to analyze the changes from health
      to disease. The first common hypothesis was the "Specific Plaque Hypothesis"
      (1976) proposing that only a few species of the total microflora are actively
      involved in disease. Secondly, the "Non-Specific Plaque Hypothesis" was updated
      (1986) and the idea that the overall activity of the total microflora could lead
      to disease, was enriched by taking into account difference in virulence among
      bacteria. Then, a hypothesis was considered that combines key concepts of the
      earlier two hypotheses: the "Ecological Plaque Hypothesis" (1994), which proposes
      that disease is the result of an imbalance in the microflora by ecological stress
      resulting in an enrichment of certain disease-related micro-organisms. Finally,
      the recent "Keystone-Pathogen Hypothesis" (2012) proposes that certain low
      abundance microbial pathogens can cause inflammatory disease by interfering with
      the host immune system and remodeling the microbiota. In this comprehensive
      review, we describe how these different hypotheses, and the ideas around them,
      arose and test their current applicability to the understanding of the
      development of oral disease. Finally, we conclude that an all-encompassing
      ecological hypothesis explaining the shifts from health to disease is still
      lacking. 

PMID- 25077074
TI  - Cellular and humoral immune responses in sheep vaccinated with candidate antigens
      MAP2698c and MAP3567 from Mycobacterium avium subspecies paratuberculosis.
AB  - Control of Johne's disease, caused by Mycobacterium avium subspecies
      paratuberculosis (MAP) in ruminants using commercially available vaccine reduces
      production losses, mortality, fecal shedding and histopathological lesions but
      does not provide complete protection from infection and interferes with
      serological diagnosis of Johne's disease and bovine tuberculosis. At this time no
      recombinant antigens have been found to provide superior protection compared to
      whole killed or live-attenuated MAP vaccines. Therefore, there is a need to
      evaluate more candidate MAP antigens. In this study recombinant MAP antigens
      MAP2698c and MAP3567 were formulated with four different MONTANIDETM (ISA 50V2,
      61VG, 71VG, and 201VG) adjuvants and evaluated for their ability to produce
      specific immune responses in vaccinated sheep. The cellular immune response was
      measured with an interferon-gamma (IFN-gamma) release assay and the humoral
      immune response was measured by antibody detection enzyme linked immunosorbent
      assay. Recombinant vaccine formulation with the antigen MAP2698c and MONTANIDETM
      ISA 201VG adjuvant produced strong whole-MAP as well as MAP2698c-specific IFN
      gamma responses in a high proportion of the vaccinated sheep. The formulation
      caused less severe injection site lesions in comparison to other formulations.
      The findings from this study suggest that the MAP2698c + 201VG should be
      evaluated in a challenge trial to determine the efficacy of this vaccine
      candidate. 

PMID- 25077075
TI  - Utilization of YouTube as a Tool to Assess Patient Perception Regarding Implanted
      Cardiac Devices.
AB  - BACKGROUND: The outreach of YouTube may have a dramatic role in the widespread
      dissemination of knowledge on implantable cardioverter devices (ICD). AIMS: This
      study was designed to review and analyze the information available on YouTube
      pertaining to implantable cardiac devices such as implantable cardioverter
      defibrillators (ICDs) and pacemakers. MATERIALS AND METHODS: YouTube was queried
      for the terms "ICD", "Implantable Cardioverter Defibrillator", and "Pacemaker".
      The videos were reviewed and categorized as according to content; number of views
      and "likes" or "dislikes" was recorded by two separate observers. RESULTS: Of the
      55 videos reviewed, 18 of the videos were categorized as patient education, 12
      were advertisements, 8 were intraoperative videos documenting the device
      implantation procedures, 7 of the videos were produced to document personal
      patient experiences, and 4 were categorized as documentation of a public event. 3
      were intended to educate health care workers. The remaining 3 were intended to
      raise public awareness about sudden cardiac death. The videos portraying
      intraoperative procedures generated the most "likes" or "dislikes" per view.
      CONCLUSION: While YouTube provides a logical platform for delivery of health
      information, the information on this platform is not regulated. Initiative by
      reputed authorities and posting accurate information in such platform can be a
      great aid in public education regarding device therapy.

PMID- 25077072
TI  - Small RNA functions in carbon metabolism and virulence of enteric pathogens.
AB  - Enteric pathogens often cycle between virulent and saprophytic lifestyles. To
      endure these frequent changes in nutrient availability and composition bacteria
      possess an arsenal of regulatory and metabolic genes allowing rapid adaptation
      and high flexibility. While numerous proteins have been characterized with regard
      to metabolic control in pathogenic bacteria, small non-coding RNAs have emerged
      as additional regulators of metabolism. Recent advances in sequencing technology
      have vastly increased the number of candidate regulatory RNAs and several of them
      have been found to act at the interface of bacterial metabolism and virulence
      factor expression. Importantly, studying these riboregulators has not only
      provided insight into their metabolic control functions but also revealed new
      mechanisms of post-transcriptional gene control. This review will focus on the
      recent advances in this area of host-microbe interaction and discuss how
      regulatory small RNAs may help coordinate metabolism and virulence of enteric
      pathogens. 

PMID- 25077076
TI  - The "fit but fat" paradigm addressed using accelerometer-determined physical
      activity data.
AB  - BACKGROUND: No studies have addressed the "fit but fat" paradigm using
      accelerometry data. AIM: The study was to determine if 1) higher levels of
      accelerometer-determined physical activity are favorably associated with
      biomarkers in overweight or obese persons (objective 1); and 2) overweight or
      obese individuals who are sufficiently active have better or similar biomarker
      levels than normal weight persons who are not sufficiently active (objective 2).
      MATERIALS AND METHODS: Data from the 2003-2006 National Health and Nutrition
      Examination Survey were analyzed and included 5,146 participants aged 20-85
      years. RESULTS: Regarding objective 1, obese active individuals had more
      favorable waist circumference, C-reactive protein, white blood cells, and
      neutrophil levels when compared to obese inactive individuals; similar results
      were found for overweight adults. Regarding objective 2, there were no
      significant differences between normal weight inactive individuals and overweight
      active individuals for nearly all biomarkers. Similarly, there were no
      significant differences between normal weight inactive individuals and obese
      active individuals for white blood cells, neutrophils, low-density lipoprotein
      cholesterol, total cholesterol, triglycerides, glucose, or homocysteine.
      CONCLUSIONS: Physical activity has a protective effect on biomarkers in normal,
      overweight, and obese individuals, and overweight (not obese) active individuals
      have a similar cardiovascular profile than normal weight inactive individuals.

PMID- 25077077
TI  - Socio-economic and nutritional determinants of low birth weight in India.
AB  - BACKGROUND: Low birth weight (LBW) is an important risk factor for childhood
      morbidity and mortality, consequently an important public health concern. AIM:
      This study aims to identify significant socio-economic and nutritional
      determinants associated with LBW in India. MATERIALS AND METHODS: Data from 2005
      to 2006 National Family Health Survey-3 (NFHS-3) of India was analyzed. A total
      of 20,946 women (15-49 years) who gave birth at least once 5 years preceding the
      NFHS-3 were included in this study. Infant's LBW (<2500 grams) as outcome
      variable was examined in association with all independent predictors as infant's
      sex, maternal household wealth status, caste, age, education, body mass index
      (BMI), stature, anemia level, parity, inter-pregnancy interval, antenatal care
      received, and living place. RESULTS: Almost 20% of the infants were born with
      LBW. Mother's low education level, BMI <18.5, short stature (height <145
      centimeters) and lack of antenatal visits (<4 visits) were significant predictors
      of LBW. Male gender has a protective effect against LBW. CONCLUSION: Maternal
      education, nutritional status and antenatal care received are key determinants
      that need to be addressed to reduce prevalence of LBW in India. Continue
      implementation of multifaceted health promotion interventions are needed to
      address these factors effectively.

PMID- 25077078
TI  - Parental Gender Equality and Use of Oral Contraceptives Among Young Women: A
      Longitudinal, Population-based Study in Sweden.
AB  - BACKGROUND: Little is known about how parental gender equality early in their
      children lives can influence daughters' decision to use contraceptive pills. AIM:
      The study aimed at exploring whether maternal working time and paternity leave in
      Sweden during the first two years of their daughters' lives is associated with
      the use of oral contraceptives when they are adolescents or young adults.
      MATERIALS AND METHODS: The study population was selected from a cohort of all
      Swedish fathers and mothers who had their first child together between 1988 and
      1989 (n = 57,520 family units). Multivariate logistic regression was used to
      estimate the association. RESULTS: Mothers' longer working time was mildly
      associated with daughters' oral contraceptive pill use, though no clear trend was
      observed. Longer paternity leave periods (>30 days) were not associated with use
      of oral contraceptives among their daughters, but 1-30 day periods showed a mild
      positive association. CONCLUSION: For maternal working time, there seems to be an
      association, but trends by working hours are not clear. There is no clear
      association between paternity leave during the first two years of their
      daughters' life and the use of oral contraceptives when they are adolescents and
      young adults.

PMID- 25077079
TI  - Determinants of underutilisation of free delivery services in an area with high
      institutional delivery rate: a qualitative study.
AB  - BACKGROUND: There has been an increase in institutional delivery rates in India
      in the recent years. However, in areas with high institutional delivery rates,
      most deliveries (>50%) occur in private institutions rather than in government
      facilities where zero expense delivery services are being provided. AIM: This
      study aimed to understand, from the community health volunteers' viewpoint, the
      reasons for underutilization of zero expense delivery services provided in
      government health facilities. MATERIALS AND METHODS: Five Focused Group
      Discussions (FGD) were conducted among Accredited Social Health Activist (ASHAs)
      of a Primary Health Centre (PHC) in Dayalpur village, Haryana in December 2012.
      Participants were asked to articulate the possible reasons that they thought were
      responsible for expectant mothers not choosing to deliver in government health
      facilities. Verbal informed consent was obtained from all participants. RESULT:
      The commonly stated reasons for underutilization of government health facilities
      for delivery services were lack of quality care, abominable behaviour of hospital
      staff, poor transportation facilities, and frequent referrals to higher centres.
      CONCLUSION: This study reflected the necessity for new policies to make
      government health facilities friendlier and more easily accessible to clients and
      to make all government hospitals follow a minimum set of standards for providing
      quality care.

PMID- 25077080
TI  - Chronic kidney disease predicts long-term mortality after major lower extremity
      amputation.
AB  - BACKGROUND: Despite low peri-operative mortality after major lower extremity
      amputation, long-term mortality remains substantial. Metabolic syndrome is
      increasing in incidence and prevalence at an alarming rate in the USA. AIM: This
      study was to determine whether metabolic syndrome predicts outcome after major
      lower extremity amputation. PATIENTS AND METHODS: A retrospective review of
      charts between July 2005 and June 2010. RESULTS: Fifty-four patients underwent a
      total of 60 major lower extremity amputations. Sixty percent underwent below-knee
      amputation and 40% underwent above-knee amputation. The 30-day mortality was 7%
      with no difference in level (below-knee amputation, 8%; above-knee amputation,
      4%; P = 0.53). The mean follow-up time was 39.7 months. The 5-year survival was
      54% in the whole group, and was independent of level of amputation (P = 0.24) or
      urgency of the procedure (P = 0.51). Survival was significantly decreased by the
      presence of underlying chronic kidney disease (P = 0.04) but not by other
      comorbidities (history of myocardial infarction, P = 0.79; metabolic syndrome, P
      = 0.64; diabetes mellitus, P = 0.56). CONCLUSION: Metabolic syndrome is not
      associated with increased risk of adverse outcomes after lower extremity
      amputation. However, patients with chronic kidney disease constitute a sub-group
      of patients at higher risk of postoperative long-term mortality and may be a
      group to target for intervention.

PMID- 25077081
TI  - Cardiovascular risks in prediabetes: preliminary data on "vasculopathy triad".
AB  - BACKGROUND: Subclinical cardiovascular disease is inherent in complications of
      diabetes mellitus. It occurs before the obvert manifestation of cardiovascular
      disease complication in diabetes, and involves vasculopathy triad or three major
      vascular events comprising stasis, endothelial dysfunction, and atherothrombosis.
      AIM: This study was to examine evidence of vasculopathy triad in prediabetes,
      biomarkers of stasis, endothelial dysfunction, and atherothrombosis in
      prediabetes were compared with apparently healthy group. MATERIALS AND METHODS:
      Eighty-one participants with results for plasma D-dimer, homocysteine, and whole
      blood viscosity were selected from a research database. The participants
      consisted of control (n = 44) and prediabetes (n = 37) based on clinical history
      and laboratory results. RESULTS: Multivariate analysis shows a significantly
      higher level of vasculopathy in prediabetes than in the control group (P >
      0.0001). Blood viscosity (P < 0.04) and homocysteine (P < 0.03) are significantly
      higher in prediabetes than in controls. Average levels for plasma D-dimer are
      also higher in prediabetes than in control, but not statistically significant in
      this particular analysis. CONCLUSION: This study suggests a novel application of
      known idea, vasculopathy triad that could be used for assessment of subclinical
      cardiovascular disease in prediabetes.

PMID- 25077082
TI  - Comparative effectiveness of chewing stick and toothbrush: a randomized clinical
      trial.
AB  - BACKGROUND: With the increasing rate of oral diseases, the global necessity of
      effective and economical products for its prevention and treatment has
      intensified. AIM: THIS STUDY WAS TO COMPARE THE EFFECTIVENESS OF TWO ORAL HYGIENE
      AIDS: Chewing stick and manual toothbrush, for plaque removal and gingival health
      after one month of a randomized clinical trial. MATERIALS AND METHODS: Dental
      students (age 18-22 years) of a public sector dental hospital were recruited.
      Sample size was determined using the American Dental Association guidelines.
      Participants were randomized into two interventional groups and provided with
      either chewing sticks or toothbrushes. Pre- and post-intervention examinations
      were executed by two blind and calibrated examiners using plaque and gingival
      dental indices. Statistical analysis included descriptive statistics, paired t
      test, and two sample independent t-tests. RESULTS: Fifty subjects were recruited
      with mean age 20 +/- 0.66 years (80% were females and 20% were males). Except for
      the mean plaque scores of toothbrush users (which increased at post-intervention
      examination), all other scores showed reduction. In contrast to the final mean
      gingival scores, a significant difference (P = < 0.0001) in the final mean plaque
      score was observed for the two respective interventional groups. CONCLUSION:
      Chewing stick has revealed parallel and at times greater mechanical and chemical
      cleansing of oral tissues as compared to a toothbrush.

PMID- 25077083
TI  - Acute Eosinophilic Myocarditis and Hyper IgE in HIV Infection: A Case Report.
AB  - CONTEXT: Eosinophilic myocarditis is a rare cause of myocarditis. It is
      manifested histopathologically by diffuse or focal myocardial inflammation with
      eosinophilic infiltration, often in association with peripheral blood
      eosinophilia. Patients infected with Human Immunodeficiency Virus (HIV),
      especially those with lower CD4 counts, can occasionally have
      hyperimmunoglobulinemia E (Hyper IgE) and eosinophilia. CASE REPORT: We report a
      case of a 29-year-old patient with Acquired Immunodeficiency Syndrome (AIDS) who
      had a persistent elevation of eosinophil counts and elevated IgE levels for a
      year prior to admission. He was presented to our emergency department with chest
      pain and laboratory tests revealed peripheral blood eosinophilia and elevated
      troponins. Coronary angiogram showed nonobstructive coronary artery disease. He
      then underwent cardiac magnetic resonance imaging which was consistent with an
      infiltrative myocarditis. After being put on steroid therapy, his peripheral
      eosinophilia resolved and his cardiac symptoms improved. CONCLUSION: Our case
      highlights that eosinophilia and Hyper IgE in HIV patients has the potential to
      contribute to end-organ damage.

PMID- 25077084
TI  - Sarcomatoid carcinoma of the lung: a model of resistance of chemotherapy.
AB  - CONTEXT: Lung tumors are very heterogeneous histological entities. Pulmonary
      sarcomatoid carcinoma is a subset of tumors characterized by specific
      histological features. Their poor prognosis compared to other lung tumors is due
      to limited responses to different types of chemotherapy. CASE REPORT: WE REPORT
      TWO PATIENTS WITH SARCOMATOID TUMORS: A 53-year-old woman and a 46-year-old man
      who presented respiratory symptoms: Dyspnea, cough, associated with a
      deterioration of general condition. CONCLUSION: Pulmonary sarcomatoid carcinomas
      remained an unexplored entity, despite their poor prognosis. Based on these
      cases, we will discuss the histological and immunohistochemical features of these
      tumors, as well as report their responses to different chemotherapy regimens used
      in the course of treatment.

PMID- 25077085
TI  - Extensive loculated ascites in hepatic amyloidosis.
AB  - CONTEXT: Amyloidosis is a disease of extracellular deposition of misfolded
      proteinaceous subunits, which could be systemic or localized disease. Though
      hepatic amyloidosis was not uncommon in autopsy series, most cases of hepatic
      amyloidosis were asymptomatic. Ascites, jaundice, portal hypertension, and
      gastrointestinal bleeding from esophageal varices were reported in literature.
      CASE REPORT: A 42-year-old man with end-stage renal disease on hemodialysis and
      recent small bowel obstruction presented with chronic abdominal pain. Computed
      tomography of abdomen and pelvis showed extensive loculated ascites and multiple
      small bowel loops tethered to adhesions and hepatomegaly. Finally, hepatic
      venography and liver biopsy confirmed hepatic amyloidosis with portal
      hypertension. The patient was waiting for liver transplant for definite
      treatment. CONCLUSION: We report a rare case of hepatic amyloidosis with prior
      small bowel obstruction presented with extensive loculated ascites and multiple
      small bowel loops tethered to adhesions.

PMID- 25077086
TI  - How are Eosinophils Supplied from Bone Marrow to Eosinophil-Infiltrated Tissues,
      When Blood Eosinophilia is Not Observed? The Case of Acute Eosinophilic
      Pneumonia.

PMID- 25077087
TI  - Congenital hyperinsulinism: current status and future perspectives.
AB  - The diagnosis and treatment of congenital hyperinsulinism (CHI) have made a
      remarkable progress over the past 20 years and, currently, it is relatively rare
      to see patients who are left with severe psychomotor delay. The improvement was
      made possible by the recent developments in the understanding of the molecular
      and pathological basis of CHI. Known etiologies include inactivating mutations of
      the KATP channel genes (ABCC8 and KCNJ11) and HNF4A, HNF1A, HADH, and UCP2 or
      activating mutations of GLUD1, GCK, and SLC16A1. The understanding of the focal
      form of KATP channel CHI and its detection by (18)F-fluoro-L-DOPA positron
      emission tomography have revolutionized the management of CHI, and many patients
      can be cured without postoperative diabetes mellitus. The incidence of the focal
      form appears to be higher in Asian countries; therefore, the establishment of
      treatment systems is even more important in this population. In addition to
      diazoxide or long-term subcutaneous infusion of octreotide or glucagon, long
      acting octreotide or lanreotide have also been used successfully until
      spontaneous remission. Because of these medications, near-total pancreatectomy is
      less often performed even for the diazoxide-unresponsive diffuse form of CHI.
      Other promising medications include pasireotide, small-molecule correctors such
      as sulfonylurea or carbamazepine, GLP1 receptor antagonists, or mammalian target
      of rapamycin inhibitors. Unsolved questions in this field include the
      identification of the remaining genes responsible for CHI, the mechanisms leading
      to transient CHI, and the mechanisms responsible for the spontaneous remission of
      CHI. This article reviews recent developments and hypothesis regarding these
      questions. 

PMID- 25077088
TI  - Phthalate exposure and childhood obesity.
AB  - Phthalates are commonly used as plasticizers and vehicles for cosmetic
      ingredients. Phthalate metabolites have documented biochemical activity including
      activating peroxisome proliferator-activated receptor and antiandrogenic effects,
      which may contribute to the development of obesity. In vitro and in vivo studies
      suggest that phthalates have significant effects on the development of obesity,
      especially after prenatal exposure at low doses. Although few studies have
      examined the effects of phthalate on obesity development in humans, some work has
      shown that phthalates affect humans and animals similarly. In this paper, we
      review the possible mechanisms of phthalate-induced obesity, and discuss evidence
      supporting the role of phthalates in the development of obesity in humans. 

PMID- 25077089
TI  - Thyroid autoimmunity in children and adolescents with newly diagnosed type 1
      diabetes mellitus.
AB  - PURPOSE: This study aim to investigate the occurrence of autoimmune thyroid
      disease in children and adolescents at onset of type 1 diabetes mellitus (T1DM)
      and to assess whether the presence of diabetes-specific autoantibodies can
      predict the autoimmune thyroid disorder. METHODS: Seventy-three children with
      T1DM were recruited. Glutamic acid decarboxylase antibodies (GADA), islet cell
      antibodies (ICA), insulin autoantibodies (IAA), and thyroid antibodies were
      determined in all patients at the time of diagnosis. RESULTS: The majority of
      patients (87.7%) had at least one pancreatic antibody (74.0% for GADA, 20.5% for
      ICA, and 24.7% for IAA). Thyroid autoantibodies were found in 19 of 73 patients
      (26.0%) at diagnosis. Thyroid autoimmunity (TA) incidence was not statistically
      significant by GADA or ICA positivity, but significantly higher by IAA positivity
      (P=0.03), and IAA positivity showed odds ratio, 4.931; 95% confidence interval,
      1.323-18.381 for TA. CONCLUSION: The IAA positivity in children and adolescents
      with TIDM was strongly related to positivity of thyroid autoantibodies and thus
      it could serve as an index for early prediction of the development of the thyroid
      autoimmune disorder among children and adolescents with TIDM.

PMID- 25077090
TI  - Fasting serum C-peptide is useful for initial classification of diabetes mellitus
      in children and adolescents.
AB  - PURPOSE: With rising obesity rates in children, it is increasingly difficult to
      differentiate between type 1 and type 2 diabetes mellitus (T1DM, T2DM) on
      clinical grounds alone. Using C-peptide as a method of classifying diabetes
      mellitus (DM) has been suggested. This study aimed to find a correlation between
      fasting C-peptide level and DM types in children and adolescents. METHODS: A
      total of 223 diabetic children, newly diagnosed at 5 hospitals between January
      2001 and December 2012, were enrolled in this study. Initial DM classification
      was based on clinical and laboratory data including fasting C-peptide at
      diagnosis; final classification was based on additional data (pancreatic
      autoantibodies, human leukocyte antigen type, and clinical course). RESULTS: Of
      223 diabetic children, 140 were diagnosed with T1DM (62.8%) and the remaining 83
      with T2DM (37.2%). The mean serum C-peptide level was significantly lower in
      children with T1DM (0.80 ng/mL) than in children with T2DM (3.91 ng/mL). Among
      223 children, 54 had a serum C-peptide level <0.6 ng/mL; they were all diagnosed
      with T1DM. The proportion of children with T2DM increased in accordance with C
      peptide level. Forty-nine of 223 children had a C-peptide level >3.0 ng/mL; 48 of
      them (97.9%) were diagnosed with T2DM. CONCLUSION: In this study, we found that
      if the C-peptide level was <0.6 ng/mL at diagnosis, T2DM could be excluded; if C
      peptide level was >3.0 ng/mL, a T1DM diagnosis is unlikely. This finding suggests
      that serum fasting C-peptide level is useful for classifying DM type at the time
      of diagnosis in youth.

PMID- 25077091
TI  - Vitamin D deficiency in Korean children: prevalence, risk factors, and the
      relationship with parathyroid hormone levels.
AB  - PURPOSE: This study was performed to investigate the relationship between serum
      vitamin D and parathyroid hormone (PTH) levels as well as to describe the
      prevalence and the risk factors of vitamin D deficiency (VDD) in Korean children.
      METHODS: Participants were 1,212 children aged 4 to 15 years, who visited Bundang
      CHA Medical Center (located at 37 degrees N) between March 2012 and February
      2013. Overweight was defined as body mass index>=85th percentile. Participants
      were divided into 4 age groups and 2 seasonal groups. VDD was defined by serum 25
      hydroxyvitamin D (25OHD) <20 ng/mL. RESULTS: The level of 25OHD was significantly
      lower in overweight group than in normal weight group (17.1+/-5.1 ng/mL vs.
      19.1+/-6.1 ng/mL, P<0.001). Winter-spring season (odds ratio [OR], 4.46; 95%
      confidence interval [CI], 3.45-5.77), older age group (OR, 1.60; 95% CI, 1.36
      1.88), and overweight (OR, 2.21; 95% CI, 1.62-3.01) were independently related
      with VDD. The PTH levels were significantly higher in VDD group compared to
      vitamin D insufficiency and sufficiency group (P<0.001). In normal weight
      children, 25OHD (beta=-0.007, P<0.001) and ionized calcium (beta=-0.594, P=0.007)
      were independently related with PTH, however, these associations were not
      significant in overweight children. CONCLUSION: VDD is very common in Korean
      children and its prevalence increases in winter-spring season, in overweight
      children and in older age groups. Further investigation on the vitamin D and PTH
      metabolism according to adiposity is required.

PMID- 25077092
TI  - Associations between serum vitamin D levels and precocious puberty in girls.
AB  - PURPOSE: Vitamin D deficiency has been linked to chronic diseases, such as
      diabetes mellitus, obesity and autoimmune disease. However, data on the vitamin D
      status and its association with precocious puberty in girls are limited. We aimed
      to investigate the association between serum 25-hydroxyvitamin D (25OHD) and
      precocious puberty in girls. METHODS: A total of 60 girls with central precocious
      puberty (CPP) and 30 control girls were enrolled. Anthropometric measurement and
      serum level of 25OHD were estimated for all subjects. RESULTS: There was a
      significant difference in the mean serum 25OHD concentration between the
      precocious puberty group and the control group (17.1+/-4.5 ng/mL vs. 21.2+/-5.0
      ng/mL, P<0.05). Forty-two of the 60 girls with CPP (70%) had vitamin D deficiency
      (defined as serum 25OHD<20 ng/mL) and 18 (30%) had vitamin D insufficiency. Of
      the 30 girls in the control group, vitamin D deficiency was seen in 13 subjects
      (43.3%), 15 subjects (50%) had vitamin D insufficiency, and 2 subjects (6.7%) had
      sufficient serum vitamin D (defined as serum 25OHD>30 ng/mL). Vitamin D deficient
      girls had a significantly higher odds ratio (OR, 3.05; 95% CI, 1.22-7.57,
      P=0.021). CONCLUSION: These results showed that vitamin D levels may be
      associated with precocious puberty. Further studies are required to establish the
      potential effect of vitamin D status on puberty.

PMID- 25077093
TI  - Gigantism caused by growth hormone secreting pituitary adenoma.
AB  - Gigantism indicates excessive secretion of growth hormones (GH) during childhood
      when open epiphyseal growth plates allow for excessive linear growth. Case one
      involved a 14.7-year-old boy presented with extreme tall stature. His random
      serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an
      oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic
      resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma.
      Transsphenoidal surgery was performed and a pituitary adenoma displaying positive
      immunohistochemical staining for GH was reported. Pituitary MRI scan was
      performed 4 months after surgery and showed recurrence/residual tumor. Medical
      treatment with a long-acting somatostatin analogue for six months was
      unsuccessful. As a result, secondary surgery was performed. Three months after
      reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205
      ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department
      for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH
      suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed
      a 6-mm-sized pituitary adenoma. Surgery was done and histopathological
      examination demonstrated a pituitary adenoma with positive staining for GH. Three
      months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was
      less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two
      cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and
      microscopic findings. 

PMID- 25077094
TI  - Denys-Drash syndrome, septated vagina and low level of anti-Mullerian hormone in
      male neonate.
AB  - There is a wide variety of genital abnormalities observed in patients with Denys
      Drash syndrome (DDS). WT1 is thought to influence the genes related to genital
      development and mutations in this gene have been associated with DDS. DDS should
      be considered in the differential diagnosis of newborns with genital anomalies.
      In contrast to other conditions with 46,XY disorders of sex development,
      individuals with DDS often have duplicated genital organs (a double vagina,
      cervix or uterus). A double uterus has not yet been reported with 1390G>A (Arg464
      Asn) mutation. However, duplicated genitals have been reported with other genetic
      mutations in patients with DDS. The duplicated genitals in DDS may be associated
      with low anti-Mullerian hormone (AMH) secretion. Measurement of the AMH levels
      may add to our understanding of variations in genital development and their
      abnormalities in disorders such as DDS. In conclusion, this is first case of low
      level of AMH and double uterus in 1390G>A (Arg464 Asn) mutations of DDS male. 

PMID- 25077095
TI  - Refractory acute suppurative thyroiditis secondary to pyriform sinus fistula.
AB  - Acute suppurative thyroiditis is a rare disease because the thyroid gland is
      remarkably resistant to infection. We present a 2-year-old girl with refractory
      acute suppurative thyroiditis due to a pyriform sinus fistula (PSF). She
      complained of fever and painful anterior neck swelling. Her condition did not
      completely improved by multiple parenteral antibiotics along with incision and
      drainage. Barium esophagogram to detect PSF demonstrated no specific finding.
      Computed tomography scan showed air bubble superior to the left thyroid gland
      which indicated a possible fistula connected to the pyriform sinus. An
      intraoperative laryngoscopy revealed a 2-mm-sized fistula opening. The fistula
      was successfully treated by chemocauterization with trichloroacetic acid. 

PMID- 25077096
TI  - A Korean boy with 46,XX testicular disorder of sex development caused by SOX9
      duplication.
AB  - The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male
      syndrome, is a rare form of DSD and clinical phenotype shows complete sex
      reversal from female to male. The sex-determining region Y (SRY) gene can be
      identified in most 46,XX testicular DSD patients; however, approximately 20% of
      patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene
      has several important functions during testis development and differentiation in
      males, and overexpression of SOX9 leads to the male development of 46,XX gonads
      in the absence of SRY. In addition, SOX9 duplication has been found to be a rare
      cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY
      negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the
      first time in Korea. He showed normal external and internal male genitalia except
      for small testes. Fluorescence in situ hybridization and polymerase chain
      reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic
      mutation was not identified by direct sequencing analysis. Therefore, we
      performed real-time PCR analyses with specific primer pairs, and duplication of
      the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare
      condition, an effort to make an accurate diagnosis is important for the provision
      of proper genetic counseling and for guiding patients in their long-term
      management. 

PMID- 25077097
TI  - Understanding the costs of cancer care before and after diagnosis for the 21 most
      common cancers in Ontario: a population-based descriptive study.
AB  - BACKGROUND: The first year after cancer diagnosis is a period of intensive
      treatment and high cost. We sought to estimate costs for the 21 most common
      cancers in Ontario in the 3-month period before and the first year after
      diagnosis. METHODS: We used the Ontario Cancer Registry to select patients who
      received diagnoses between 1997 and 2007 at 19 years of age or older, with valid
      International Classification of Diseases for Oncology (ICD-O) and histology
      codes, who survived 30 days or longer after diagnosis and had no second cancer
      within 90 days of the initial cancer (n = 402 399). We used linked administrative
      data to calculate mean costs for each cancer during the pre- and postdiagnosis
      periods for patients who died within 1 year after diagnosis and patients who
      survived beyond 1 year after diagnosis. RESULTS: Mean prediagnosis costs were
      $2060 (95% confidence interval [CI] $2023-$2098) for all patients with cancer.
      Costs ranged from $890 (95% CI $795-$985) for melanoma to $4128 (95% CI $3591
      $4664) for liver cancer among patients who survived beyond 1 year after
      diagnosis, and ranged from $2188 (95% CI $2040-$2336) for esophageal cancer to
      $5142 (95% CI $4664-$5620) for multiple myeloma among patients who died within 1
      year. The mean postdiagnosis cost for our cohort was $25 914 (95% CI $25 782-$26
      046). Mean costs were lowest for melanoma ($8611 [95% CI $8221-$9001]) and
      highest for esophageal cancer ($50 620 [95% CI $47 677-$53 562] among patients
      who survived beyond 1 year after diagnosis, and ranged from $27 560 (95% CI $25
      747-$29 373) for liver cancer to $81 655 (95% CI $58 361-$104 949) for testicular
      cancer among patients who died within 1 year. INTERPRETATION: Our research
      provides cancer-related cost estimates for the pre- and postdiagnosis phases and
      offers insight into the economic burden incurred by the Ontario health care
      system. These estimates can help inform policy-makers' decisions regarding
      resource allocation for cancer prevention and control, and can serve as important
      input for economic evaluations.

PMID- 25077098
TI  - The consumption of alcohol mixed with energy drinks: prevalence and key
      correlates among Canadian high school students.
AB  - BACKGROUND: An emerging body of research has reported high consumption of alcohol
      mixed with energy drinks among young adults, particularly college students.
      However, little is known about adolescents' consumption of these drinks. The
      purpose of this study was to determine the prevalence of consumption of alcohol
      mixed with energy drinks and to examine its correlates among Canadian high school
      students. METHODS: We used a nationally representative sample of 36 155 Canadian
      students in grades 7 to 12 who participated in the 2010/2011 Youth Smoking
      Survey. RESULTS: About 20% of Canadian high school students reported consuming
      alcohol mixed with energy drinks in the last year, with considerable variation
      across provinces. Multivariate logistic regression analyses showed that the odds
      of consumption of these drinks were higher among students in lower grades (grades
      7 and 8) and among students who identified their ethnicity as black or "other."
      Consumption of alcohol mixed with energy drinks was positively associated with
      substance use (current smoking [adjusted odds ratio (OR) 1.52, 95% confidence
      interval (CI) 1.19-1.95], past-year heavy drinking [adjusted OR 3.41, 95% CI 2.84
      4.09] and marijuana use [adjusted OR 2.29, 95% CI 1.90-2.76]), absence from
      school, participation in school team sports and having more weekly spending
      money. Students who felt more connected to school and had an academic average of
      70% or higher were less likely to consume alcohol mixed with energy drinks.
      INTERPRETATION: The consumption of alcohol mixed with energy drinks is an
      emerging public health concern. Consumption of these drinks is substantial among
      Canadian high school students and can lead to many potential harms, both acute
      (e.g., injury) and long term (e.g., increased alcohol dependence). Our findings
      highlight the need for further research into the long-term effects of consumption
      of alcohol mixed with energy drinks among young people, as well as the
      development of interventions aimed at reducing consumption of these drinks.

PMID- 25077099
TI  - Opioid therapy for refractory dyspnea in patients with advanced chronic
      obstructive pulmonary disease: patients' experiences and outcomes.
AB  - BACKGROUND: Dyspnea that is refractory to conventional treatments affects up to
      50% of patients with advanced chronic obstructive pulmonary disease (COPD).
      Although professional societies recommend opioids in this setting, evidence
      supporting their use over months is limited. We conducted a multicentre mixed
      methods study to understand patients' experiences when opioids are added to
      optimized conventional treatments for advanced COPD. METHODS: A total of 44
      patients (median age 74, range 51-89 years) agreed to participate in this 6-month
      study. After baseline assessments, immediate-release morphine sulfate syrup
      (initially 0.5 mg twice daily) was slowly titrated upward based on weekly
      assessments of symptoms. We conducted semistructured interviews and collected
      contemporaneous measures of health-related quality of life, severity of dyspnea,
      anxiety, depression, global ratings of opioid "helpfulness" and adverse effects
      before, at 2 months and at 4-6 months after opioids were started. RESULTS: Of the
      44 patients, 32 (73%) completed the trial; 27 (90%) of 30 patients reported the
      opioid treatment as very (43%) or somewhat (47%) helpful. Three main themes
      emerged from the patients' overall positive experiences: small gains have big
      impact; realign hopes with reality; and "try it." Significant improvements were
      observed in median (interquartile range) scores between baseline and 4-6 months'
      assessment for health-related quality of life (Chronic Respiratory Questionnaire:
      3.5 [2.8-4.0] v. 4.2 [3.6-4.8]; and Chronic Respiratory Questionnaire-Dyspnea
      domain: 2.8 [2.3-3.6] v. 3.9 [2.8-4.5]) and decreases in severity of dyspnea
      (numerical rating scale: 7.0 [5.0-8.0] v. 5.0 [4.0-6.0]). Adverse effects were
      minimal for most patients. INTERPRETATION: Opioids were a helpful and acceptable
      intervention for refractory dyspnea in patients with advanced COPD. Many of the
      patients experienced sustained benefits over months, which supports recent
      recommendations to consider opioids in this setting. TRIAL REGISTRATION:
      ClinicalTrial.gov, no. NCT00982891.

PMID- 25077100
TI  - Comparison of blood pressure measurements using an automated blood pressure
      device in community pharmacies and family physicians' offices: a randomized
      controlled trial.
AB  - BACKGROUND: Accurate measurement of blood pressure is the foundation of
      appropriate diagnosis, treatment and ongoing management of hypertension. The use
      of automated blood pressure devices in community settings such as pharmacies
      provide opportunities for additional blood pressure measurement; however, it is
      important to ensure that these measurements are comparable to those taken in
      physicians' offices using the same devices. We conducted a randomized controlled
      trial to assess whether blood pressure readings assessed by use of an automated
      device differed according to the setting, specifically in community pharmacies
      and family physicians' offices. METHODS: We included adults aged 65 years and
      older who did not live in long-term care facilities or in hospital. The trial was
      administered by volunteer peer health educators, family physicians and
      pharmacists in 2 midsized communities in Ontario from April to September 2010.
      The 5 participating family physicians mailed invitations to their eligible
      patients. Those who gave informed consent were randomly allocated to 1 of 2
      assessment sequences: group A had their blood pressure measured at their
      physician's office, then at a pharmacy, then again at their physician's office;
      those in group B had their blood pressure measured at a pharmacy, then at their
      physician's office, then again at a pharmacy. An automated blood pressure device
      (BpTRU) was used in both settings. We calculated the differences in mean systolic
      and diastolic blood pressure, and we compared the readings at both settings and
      by sequence of assessment. RESULTS: In total, 275 adults completed the trial
      (mean age 75.9 yr, 49.5% male, 46.9% with a self-reported diagnosis of
      hypertension). There were no statistically significant differences in systolic or
      diastolic blood pressure measurements associated with the sequence of assessment
      or the setting. There was a significant difference in the overall mean systolic
      blood pressure between the 2 assessment sequences (group A 122.0 v. group B 127.8
      mm Hg, p < 0.001). INTERPRETATION: Automated devices used in pharmacies to
      measure blood pressure provide accurate and valid information that can be used in
      the diagnosis and management of hypertension among older adults in the community.
      TRIAL REGISTRATION: www.controlled-trials.com, no. ISRCTN91799042.

PMID- 25077101
TI  - Effect of latitude on the rate of change in incidence of Lyme disease in the
      United States.
AB  - BACKGROUND: Tick-borne illnesses represent an important class of emerging
      zoonoses, with climate change projected to increase the geographic range within
      which tick-borne zoonoses might become endemic. We evaluated the impact of
      latitude on the rate of change in the incidence of Lyme disease in the United
      States, using publicly available data. METHODS: We estimated state-level year-on
      year incidence rate ratios (IRRs) for Lyme disease for the period 1993 to 2007
      using Poisson regression methods. We evaluated between-state heterogeneity in
      IRRs using a random-effects meta-analytic approach. We identified state-level
      characteristics associated with increasing incidence using random-effects meta
      regression. RESULTS: The incidence of Lyme disease in the US increased by about
      80% between 1993 and 2007 (IRR per year 1.049, 95% CI [confidence interval] 1.048
      to 1.050). There was marked between-state heterogeneity in the average incidence
      of Lyme disease, ranging from 0.008 per 100 000 person-years in Colorado to 75
      per 100 000 in Connecticut, and significant between-state heterogeneity in
      temporal trends (p < 0.001). In multivariable meta-regression models, increasing
      incidence showed a linear association with state latitude and population density.
      These 2 factors explained 27% of the between-state variation in IRRs. No
      independent association was identified for other state-level characteristics.
      INTERPRETATION: Lyme disease incidence increased in the US as a whole during the
      study period, but the changes were not uniform. Marked increases were identified
      in northern-most states, whereas southern states experienced stable or declining
      rates of Lyme disease.

PMID- 25077102
TI  - Metabolite measurements in the caudate nucleus, anterior cingulate cortex and
      hippocampus among patients with mitochondrial disorders: a case-control study
      using proton magnetic resonance spectroscopy.
AB  - BACKGROUND: Mitochondrial disorders are clinical syndromes associated with
      mutations in the mitochondrial or nuclear genome that result in impaired
      oxidative phosphorylation and deficient energy production. Metabolic
      abnormalities in brain areas associated with cognitive functions could give rise
      to neuropsychiatric symptomatology. The aim of this study was to use single-voxel
      proton magnetic resonance spectroscopy to identify metabolic abnormalities in
      regions implicated in neuropsychiatric symptoms in patients with mitochondrial
      disorders. METHODS: N-acetyl-aspartate and creatine levels were measured in the
      caudate nucleus, anterior cingulate cortex and hippocampus in 15 patients with
      mitochondrial disorders compared with 15 healthy controls matched for age and
      sex. RESULTS: N-acetyl-aspartate levels were significantly lower in the caudate
      nucleus among patients with mitochondrial disorders (mean 7.04 +/- 1.19 standard
      deviation [SD] institutional units) compared with healthy controls (mean 8.19 +/-
      1.18 SD institutional units; p = 0.02). Creatine levels were lower in the caudate
      nucleus among patients compared with controls (patients: mean 6.84 +/- 1.42 SD
      institutional units; controls: mean 7.52 +/- 0.76 SD institutional units; p =
      0.03), but the results were no longer significant after correction for multiple
      comparisons. There were no significant differences in metabolite measurements
      between patients and controls in the anterior cingulate cortex and the
      hippocampus. INTERPRETATION: Metabolic abnormalities were identified exclusively
      in the caudate nucleus, with significantly lower N-acetyl-aspartate levels among
      patients compared with controls. These results suggest that the corpus striatum
      may be highly susceptible to mitochondrial oxidative phosphorylation defects and
      resultant cell loss. Given the role of the caudate nucleus in cognitive and
      executive functions, our findings raise the possibility that metabolic
      abnormalities in the caudate nucleus may contribute to cognitive impairment and
      neuropsychiatric symptoms in patients with mitochondrial disorders, which could
      be investigated in future studies.

PMID- 25077103
TI  - Salmonella enterica serotype Typhi infections in a Canadian pediatric hospital: a
      retrospective case series.
AB  - BACKGROUND: In developed countries, typhoid fever generally occurs in travellers
      or recent immigrants from endemic areas. Our aim was to describe the epidemiology
      of Salmonella enterica serotype Typhi infections among children presenting to a
      pediatric teaching hospital in Montreal, Quebec. METHODS: We included all
      patients less than 18 years of age who presented to the Montreal Children's
      Hospital between 1991 and 2011 with a laboratory-confirmed diagnosis of typhoid
      fever (Salmonella enterica ser. Typhi isolated from blood or stool) in a
      retrospective case series. RESULTS: During the study period, we identified 39
      cases of typhoid fever (mean age of patient 7.5 yr). Four (10.3%) of these cases
      occurred in newly arrived immigrants shortly after their arrival in Canada
      (median 15.5 d). Most cases (76.9%) occurred in children who had visited friends
      and relatives in their home country. None of the travellers had received a
      vaccination against typhoid fever before their departure. All cases presented
      with high fever (mean temperature 40.4 degrees C) that lasted for a mean of 15.8
      days. Common accompanying symptoms included anorexia, abdominal pain, vomiting
      and diarrhea. All 39 isolates of S. enterica ser. Typhi were susceptible to third
      generation cephalosporins, and 7 were resistant to ciprofloxacin. Ampicillin
      resistance occurred in 10 (25.6%) of the isolates. No deaths occurred among the
      study participants. INTERPRETATION: Most cases of typhoid fever occurred in
      children who had travelled to endemic areas to visit friends and relatives. Thus,
      there is a role for increased awareness on the part of family physicians and
      pediatricians caring for these children to discuss travel-related infections
      during regularly scheduled appointments, because parents might not consult travel
      clinics or discuss their travel plans before travelling back to their home
      country.

PMID- 25077104
TI  - Rates and determinants of exclusive breastfeeding in first 6 months among women
      in Nova Scotia: a population-based cohort study.
AB  - BACKGROUND: Despite compelling evidence that exclusive breastfeeding for the
      first 6 months of life provides important health benefits to both mothers and
      their infants, most mothers do not follow this practice. We conducted a study to
      identify predictors of early cessation of exclusive breastfeeding (before 6
      months after delivery). METHODS: For this population-based longitudinal cohort
      study, we linked data from a perinatal database and a public health database for
      infants born between 2006 and 2009 in 2 regions in the province of Nova Scotia,
      Canada. The cohort was followed from the mother's first prenatal visit until her
      infant was 6 months old. Hazard ratios (HRs) for early cessation of exclusive
      breastfeeding were determined through Cox proportional hazards regression
      modelling. RESULTS: Overall, 64.1% (2907/4533) of the mothers in the cohort
      initiated breastfeeding. Only 10.4% (413/3957) exclusively breastfed for the
      recommended 6 months. The largest drop in exclusive breastfeeding occurred within
      the first 6 weeks after birth. Among the mothers who initiated breastfeeding,
      significant predictors of early cessation of exclusive breastfeeding identified
      by multivariable modelling included less than high school education (HR 1.66, 95%
      confidence interval [CI] 1.35-2.04), lowest neighbourhood income quintile (HR
      1.35, 95% CI 1.13-1.60), single motherhood (HR 1.24, 95% CI 1.10-1.41),
      prepregnancy obesity (HR 1.43, 95% CI 1.23-1.65), smoking throughout pregnancy
      (HR 1.39, 95% CI 1.21-1.60), no early breast contact by the infant (< 1 hour
      after birth) (HR 1.44, 95% CI 1.29-1.62) and no intention to breastfeed (HR 1.78,
      95% CI 1.44-2.16). INTERPRETATION: We found that most predictors of early
      cessation of breastfeeding were intertwined with social determinants of health.
      However, we identified potentially modifiable risk factors. Providing
      opportunities for early breast contact by the infant and continued efforts in
      smoking cessation and obesity reduction may contribute to a longer duration of
      exclusive breastfeeding.

PMID- 25077105
TI  - Early cholecystectomy for acute cholecystitis: a population-based retrospective
      cohort study of variation in practice.
AB  - BACKGROUND: Despite evidence in favour of early cholecystectomy for most patients
      with acute cholecystitis, variation in practice has been reported across
      hospitals worldwide. We sought to characterize the extent and potential sources
      of variation in the performance of early cholecystectomy for acute cholecystitis
      within a large regional health care system. METHODS: We used a population-based
      retrospective cohort design. The cohort was limited to adults with a first
      episode of acute cholecystitis, admitted through the emergency department.
      Patients were identified using administrative databases comprising all emergency
      department visits and hospital admissions in Ontario from 2004 to 2010. Patient
      and hospital characteristics associated with early cholecystectomy (within 7 d of
      emergency department presentation) were identified using multilevel logistic
      regression. RESULTS: We identified 24 437 patients admitted to 106 hospitals with
      a first episode of acute cholecystitis. Most (58%, n = 14 286) underwent early
      cholecystectomy. Rates of early cholecystectomy varied widely across hospitals
      (median 51%, interquartile range [IQR] 25%-72%), even among healthy patients aged
      18-49 years with uncomplicated cholecystitis (median 74%, IQR 41%-88%).
      Multivariable multilevel analysis showed that hospitals in the lowest quartile
      for volume of acute cholecystitis admissions had the lowest adjusted odds of
      early cholecystectomy (odds ratio 0.53, 95% confidence interval 0.35-0.78) and
      that hospital effects accounted for half (27%) of the explained variation (53%)
      in early cholecystectomy. INTERPRETATION: Across the hospitals of a regional
      health care system, similar patients with acute cholecystitis did not receive
      comparable care. Hospital-specific initiatives should be considered to facilitate
      early cholecystectomy for patients with acute cholecystitis.

PMID- 25077106
TI  - Mortality in a large community-based cohort of inner-city residents in Vancouver,
      Canada.
AB  - BACKGROUND: The Downtown Eastside is a robust and densely populated neighbourhood
      in Vancouver, Canada, that is characterized by low-income housing and drug use
      and a high prevalence of HIV infection. We evaluated mortality and excess
      mortality among the broader community of individuals living in this
      neighbourhood. METHODS: The Community Health and Safety Evaluation is a community
      based study of inner-city residents in the Downtown Eastside who were recruited
      in 2003 and 2004. Participants' data were linked with data in provincial virology
      and mortality databases retrospectively and prospectively for the period 1991
      2009. Mortality and standardized mortality ratios (SMRs) were calculated for the
      period 2003-2009 to compare death rates in the study population with rates in the
      population of Vancouver. RESULTS: Among 2913 participants, 374 deaths occurred,
      for an all-cause mortality of 223 per 10 000 person-years (95% confidence
      interval [CI] 201-247 per 10 000 person-years). Compared with the population of
      Vancouver, significant excess mortality was observed in the study population (SMR
      7.1, 95% CI 6.4-7.9). Excess mortality was higher among women (SMR 15.4, 95% CI
      12.8-18.5) than among men (SMR 5.8, 95% CI 5.1-6.6). Although crude mortality
      increased with age, excess mortality was greatest among participants less than 35
      years old (SMR 13.2, 95% CI 9.4-18.5) and those 35-39 years old (SMR 13.3, 95% CI
      10.3-17.1). Excess risk was also elevated among participants with hepatitis C
      virus (HCV), HIV and HCV/HIV infection, with SMRs of 5.9 (95% CI 4.9-7.1), 19.2
      (95% CI 12.8-28.9) and 23.0 (95% CI 19.3-27.4), respectively. INTERPRETATION: Our
      study showed high mortality in this inner-city population, particularly when
      compared with the general population of Vancouver. Excess mortality was highest
      among women, younger participants and those infected with either HCV or HIV or
      both.

PMID- 25077107
TI  - Effect of vitamin D status on clinical pregnancy rates following in vitro
      fertilization.
AB  - BACKGROUND: Recent studies suggest that vitamin D may play a role in human
      reproduction. Our goal was to investigate whether vitamin D levels are predictive
      of implantation and clinical pregnancy rates in infertile women following in
      vitro fertilization (IVF). METHODS: We prospectively evaluated vitamin D status,
      as determined by serum 25-hydroxy-vitamin D (25[OH]D) levels, in a cohort of 173
      women undergoing IVF at Mount Sinai Hospital, Toronto, Ontario. Serum 25(OH)D
      samples were collected within 1 week before oocyte retrieval. We classified
      patients as having sufficient (>= 75 nmol/L) or insufficient (or deficient;
      hereafter referred to as "insufficient"; < 75 nmol/L) serum levels of 25(OH)D. We
      compared patient demographics and IVF cycle parameters between groups. The
      primary outcome measure was clinical pregnancy (intrauterine sac visible on
      ultrasound performed 4-5 weeks after embryo transfer). RESULTS: Of the included
      women, 54.9% had insufficient 25(OH)D levels and 45.1% had sufficient levels.
      Women with sufficient levels had significantly higher rates of clinical pregnancy
      per IVF cycle started (52.5%) compared with women with insufficient levels
      (34.7%; p < 0.001). Implantation rates were also higher in the sufficient 25(OH)D
      group, but the results were not statistically significant. Multivariable logistic
      regression analysis (adjusted for age, body mass index and day 5 [v. day 3]
      embryo transfer) showed that serum 25(OH)D level may be a predictor of clinical
      pregnancy (adjusted odds ratio 1.01, 95% confidence interval 1.00-1.03).
      INTERPRETATION: Our findings suggest that women with sufficient levels of vitamin
      D are significantly more likely to achieve clinical pregnancy following IVF.
      Vitamin D supplementation could provide an easy and cost-effective way of
      improving pregnancy rates; this merits further investigation. TRIAL REGISTRATION:
      ClinicalTrials.gov, no. NCT01348594.

PMID- 25077108
TI  - Estimating the payoffs from cardiovascular disease research in Canada: an
      economic analysis.
AB  - BACKGROUND: Investments in medical research can result in health improvements,
      reductions in health expenditures and secondary economic benefits. These
      "returns" have not been quantified in Canada. Our objective was to estimate the
      return on cardiovascular disease research funded by public or charitable
      organizations. METHODS: Our primary outcome was the internal rate of return on
      cardiovascular disease research funded by public or charitable sources. The
      internal rate of return is the annual monetary benefit to the economy for each
      dollar invested in cardiovascular disease research. Calculation of the internal
      rate of return involved the following: measuring expenditures on cardiovascular
      disease research, estimating the health gains accrued from new treatments for
      cardiovascular disease, determining the proportion of health gains attributable
      to cardiovascular disease research and the time lag between research expenditures
      and health gains, and estimating the spillovers from public- or charitable-sector
      investments to other sectors of the economy. RESULTS: Expenditures by public or
      charitable organizations on cardiovascular disease research from 1981 to 1992
      amounted to $392 million (2005 dollars). Health gains associated with new
      treatments from 1994 to 2005 (13-yr lag) amounted to 2.2 million quality-adjusted
      life-years. We calculated an internal rate of return of 20.6%. CONCLUSION:
      Canadians obtain relatively high health and economic gains from investments in
      cardiovascular disease research. Every $1 invested in cardiovascular disease
      research by public or charitable sources yields a stream of benefits of roughly
      $0.21 to the Canadian economy per year, in perpetuity.

PMID- 25077109
TI  - Variation between Canadian centres in the uptake of treatment for hepatitis C by
      patients coinfected with HIV: a prospective cohort study.
AB  - BACKGROUND: Uptake of treatment for hepatitis C virus (HCV) is low in Canada
      despite its publicly funded health care system. We explored the uptake of HCV
      treatment within the Canadian Co-infection Cohort to determine if some treatment
      centres have been more successful than others at starting patients with HIV-HCV
      coinfection on HCV treatment. METHODS: We estimated the variation between 16
      centres in the uptake of HCV treatment using a Weibull time-to-event model with
      adjustment for patient characteristics that are thought likely to influence the
      uptake of treatment. We asked the principal investigator at each centre about
      access to hepatitis-related specialists and services and the importance of
      various criteria when determining if a patient with HIV-HCV coinfection should
      receive treatment for HCV. RESULTS: Among 681 untreated patients in the Canadian
      Co-infection Cohort, 163 patients with HIV-HCV coinfection started HCV treatment
      over a period of 1827 patient-years (9 per 100 patient-years). Even after
      adjustment for case mix, there was still appreciable variation in treatment
      uptake between centres, with mean hazard ratios of 0.43 (95% credible interval
      0.11-1.3) and 3.6 (95% credible interval 1.7-8.4) for the centres least and most
      likely to start an average patient with HIV-HCV coinfection on HCV treatment. The
      most important criteria reported by principal investigators for determining
      eligibility for treatment were severity of fibrosis, current psychiatric
      comorbidities, current alcohol intake, past HCV treatment and a history of
      reinfection with HCV. However, the opinions were wide-ranging: 8 of the 15
      criteria elicited both the responses "less important" and "very important."
      INTERPRETATION: The magnitude of the centre effects and diverse opinions about
      the importance of treatment eligibility criteria suggest that provider-related
      barriers to HCV treatment uptake are as important as patient-related barriers.

PMID- 25077110
TI  - Prescribing patterns of novel oral anticoagulants following regulatory approval
      for atrial fibrillation in Ontario, Canada: a population-based descriptive
      analysis.
AB  - BACKGROUND: The clinical armamentarium for anticoagulation has expanded
      substantially since the recent approval of dabigatran, rivaroxaban and apixaban
      for the prevention of stroke in atrial fibrillation. However, patients in the
      general population often differ from participants in clinical trials. In this
      study, we assessed the uptake of these novel oral anticoagulants in Ontario,
      Canada, within the first 2 years after dabigatran's approval for this indication.
      METHODS: Using data on province-wide prescription volumes, we conducted a time
      series analysis of prescription trends between October 2010 and September 2012
      for all orally administered anticoagulants (warfarin, dabigatran and rivaroxaban)
      that were available in this period. We stratified dabigatran prescription rates
      by age group (20-39, 40-59, 60-64, 65-84 and >= 85 yr). We compared the
      proportion of dabigatran prescriptions to patients aged 65 or older with similar
      data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY)
      study. RESULTS: Over the 24-month study period, we found that prescriptions for
      the novel anticoagulants rose more than 20-fold, to represent 21.1% of all
      prescriptions of oral anticoagulants by September 2012. The rise in prescriptions
      was due primarily to an increase in dabigatran use. Prescription rates of
      dabigatran were highest among people aged 85 years or more, a group at increased
      risk of bleeding who are markedly older than the average participant in the
      clinical trial in which the drug was tested (71 yr). In September 2012, most of
      the dabigatran prescriptions were for the lower-dose formulation (110 mg) in the
      older groups (58.8% of dabigatran prescriptions in the 65-84 age group and 93.6%
      in the oldest group). INTERPRETATION: We observed rapid growth in the uptake of
      the novel oral anticoagulants since their approval for use in patients with
      atrial fibrillation, especially among those aged 85 years or more. This increase
      in use in the oldest group, a population at high risk of bleeding, signals the
      need to evaluate outcomes of use of novel oral anticoagulants in the clinical
      setting.

PMID- 25077111
TI  - Effects of implementing electronic medical records on primary care billings and
      payments: a before-after study.
AB  - BACKGROUND: Several barriers to the adoption of electronic medical records (EMRs)
      by family physicians have been discussed, including the costs of implementation,
      impact on work flow and loss of productivity. We examined billings and payments
      received before and after implementation of EMRs among primary care physicians in
      the province of Ontario. We also examined billings and payments before and after
      switching from a fee-for-service to a capitation payment model, because EMR
      implementation coincided with primary care reform in the province. METHODS: We
      used information from the Electronic Medical Record Administrative Data Linked
      Database (EMRALD) to conduct a retrospective before-after study. The EMRALD
      database includes EMR data extracted from 183 community-based family physicians
      in Ontario. We included EMRALD physicians who were eligible to bill the Ontario
      Health Insurance Plan at least 18 months before and after the date they started
      using EMRs and had completed a full 18-month period before Mar. 31, 2011, when
      the study stopped. The main outcome measures were physicians' monthly billings
      and payments for office visits and total annual payments received from all
      government sources. Two index dates were examined: the date physicians started
      using EMRs and were in a stable payment model (n = 64) and the date physicians
      switched from a fee-for-service to a capitation payment model (n = 42). RESULTS:
      Monthly billings and payments for office visits did not decrease after the
      implementation of EMRs. The overall weighted mean annual payment from all
      government sources increased by 27.7% after the start of EMRs among EMRALD
      physicians; an increase was also observed among all other primary care physicians
      in Ontario, but it was not as great (14.4%). There was a decline in monthly
      billings and payments for office visits after physicians changed payment models,
      but an increase in their overall annual government payments. INTERPRETATION:
      Implementation of EMRs by primary care physicians did not result in decreased
      billings or government payments for office visits. Further economic analyses are
      needed to measure the effects of EMR implementation on productivity and the costs
      of implementing an EMR system, including the costs of nonclinical work by
      physicians and their staff.

PMID- 25077112
TI  - Trends in compensation for deaths from occupational cancer in Canada: a
      descriptive study.
AB  - BACKGROUND: Occupational cancer is the leading cause of work-related deaths, yet
      it is often unrecognized and under reported, and associated claims for
      compensation go unfiled. We sought to examine trends in deaths from occupational
      cancer, high-risk industries and exposures, and commonly compensated categories
      of occupational cancers. In addition, we compared deaths from occupational lung
      cancer for which compensation had been given with total deaths from lung cancer.
      METHODS: We used data from the Association of Workers' Compensation Boards of
      Canada pertaining to the nature and source of the injury or disease and the
      industry in which it occurred (by jurisdiction) to describe trends in compensated
      claims for deaths from occupational cancer in Canada for the period 1997-2010. We
      used data published by the Canadian Cancer Society in Canadian Cancer Statistics
      to compare compensated occupational lung cancer deaths with total estimated lung
      cancer deaths for the period between 2006 and 2010. RESULTS: Compensated claims
      for deaths from occupational cancer have increased in recent years and surpassed
      those for traumatic injuries and disorders in Canada, particularly in Ontario.
      Between 1997 and 2010, one-half of all compensated deaths from occupational
      cancer in Canada were from Ontario. High-risk industries for occupational cancer
      include manufacturing, construction, mining and, more recently, government
      services. Deaths from lung cancer and mesothelioma comprise most of the
      compensated claims for deaths from occupational cancer in Ontario and Canada.
      These diseases are usually the result of asbestos exposure. The burden of other
      occupational carcinogens is not reflected in claims data. INTERPRETATION:
      Although the number of accepted claims for deaths from occupational cancers has
      increased in recent years, these claims likely only represent a fraction of the
      true burden of this problem. Increased education of patients, workers at high
      risk of exposure and health care providers is needed to ensure that people with
      work-related cancer are identified and file a claim for compensation.

PMID- 25077113
TI  - Comparison of orally administered bisphosphonate drugs in reducing the risk of
      hip fracture in older adults: a population-based cohort study.
AB  - BACKGROUND: Orally administered bisphosphonate drugs (i.e., alendronate,
      etidronate, risedronate) can reduce the risk of vertebral fracture. However, only
      alendronate and risedronate have proven efficacy in reducing the risk of hip
      fracture. We sought to examine the comparative effectiveness of orally
      administered bisphosphonate drugs in reducing hip fractures among older adults.
      METHODS: We identified new users of orally administered bisphosphonate drugs in
      British Columbia and Ontario between 2001 and 2008. We used province- and sex
      specific propensity score-matching strategies to maximize comparability between
      exposure groups. We used Cox proportional hazards models to compare time-to-hip
      fracture within 1 year of treatment between exposures by sex in each province.
      Our secondary analyses considered hip fracture rates within 2 and 3 years' follow
      up. We used alendronate as the reference for all comparisons and pooled
      provincial estimates using random effects variance-weighted meta-analysis.
      RESULTS: We identified 321 755 patients who were eligible for inclusion in the
      study. We found little difference in fracture rates between men (pooled hazard
      ratio [HR] 0.94, 95% confidence interval [CI] 0.74-1.14) or women (pooled HR
      1.15, 95% CI 0.73-1.56) taking risedronate and those taking alendronate. We
      similarly identified little difference in fracture rates between women taking
      etidronate and those taking alendronate (pooled HR 1.00, 95% CI 0.82-1.18).
      However, we identified lower rates of hip fracture among men taking etidronate
      relative to alendronate (pooled HR 0.77, 95% CI 0.60-0.94). Results extended to 2
      and 3 years' follow-up were similar. However, with 3 years' follow-up, rates of
      hip fracture were lower among women in British Columbia who had taken
      alendronate. INTERPRETATION: We identified little overall difference between
      alendronate and risedronate in reducing the risk of hip fracture in men or women.
      Our finding that etidronate is associated with lower fracture risk among men is
      likely due to selection bias. The long-term comparative effects of orally
      administered bisphosphonate drugs warrant further study.

PMID- 25077114
TI  - Prescribed targets for titration of vasopressors in septic shock: a retrospective
      cohort study.
AB  - BACKGROUND: Without robust clinical evidence to guide titration of vasopressors
      in septic shock, it is unclear how dosing of these potent medications occurs. We
      sought to measure the proportion of vasopressor prescriptions for septic shock
      that were missing explicit targets and to describe the targets that we
      identified. METHODS: We conducted a multicentre, retrospective cohort study
      involving 9 intensive care units (ICUs) located at 3 academic hospitals in Canada
      and Australia. We reviewed charts of consecutive patients aged 18 years or older
      who were admitted to the ICU for a presumptive diagnosis of sepsis. Other
      inclusion criteria were hypotension (systolic arterial pressure <= 90 mm Hg or
      mean arterial pressure [MAP] <= 65 mm Hg) and continuous infusion of vasopressors
      for at least 1 hour within the initial 48 hours of ICU stay, the period of
      observation for this study. RESULTS: We included data from 369 patient charts. At
      least 1 target was specified in 99% of charts. The most common targets were MAP
      measurements (73%). The median initial MAP target was 65 (range 55-90) mm Hg. In
      multivariable regression models, hospital site and older age of the patient, but
      not comorbidities of the patient, were associated with MAP targets. In 40% of
      patients, the treating team modified the initial target at least once.
      INTERPRETATION: This study suggests that an explicit blood pressure target
      accompanies nearly every vasopressor prescription and that patient
      characteristics have little influence on its value. Identification of a titration
      strategy that will maximize benefit and minimize harm constitutes a research
      priority.

PMID- 25077115
TI  - Stage, treatment and outcomes for patients with breast cancer in British Columbia
      in 2002: a population-based cohort study.
AB  - BACKGROUND: There are very few long-term Canadian data on breast cancer outcomes
      by stage. We described the stage, treatment and outcomes of breast cancer at a
      population level for patients in British Columbia. METHODS: This population-based
      cohort study included almost all patients with incident breast cancer registered
      in 2002 (about 97.6% registry case completeness). For these patients, information
      on stage, primary local surgery, radiotherapy, chemotherapy, hormone therapy and
      survival outcome (based on registry date and cause-of-death data) were available.
      We calculated Kaplan-Meier curves for breast cancer-specific survival and overall
      survival by stage and analyzed prognostic and treatment factors with a
      multivariable Cox model. RESULTS: The 2927 incident cases of breast cancer
      identified in 2002 had the following distribution by stage: stage 0 (in situ),
      424 (14%); stage I, 1118 (38%); stage II, 938 (32%); stage III, 233 (8%); stage
      IV, 123 (4%); unknown, 91 (3%). The distribution of patients' ages was < 40
      years, 127 (4%); 40-49, 538 (18%); 50-59, 719 (25%); 60-69, 660 (23%); 70-79, 583
      (20%); >= 80, 300 (10%). Within the first year after diagnosis, radiotherapy was
      provided to 1649 patients (56%), chemotherapy to 928 (32%) and hormone therapy to
      1664 (57%). Ten-year breast cancer-specific survival rates by stage were > 99%
      for stage 0, 95% for stage I, 81% for stage II, 55% for stage III and 4% for
      stage IV. Ten-year overall survival rates were 89% for stage 0, 81% for stage I,
      68% for stage II, 43% for stage III and 2% for stage IV. INTERPRETATION: This
      analysis provides a Canadian benchmark for treatment rates and 10-year outcomes
      by stage for all incident cases of breast cancer in a single province. Outcomes
      in British Columbia compared well with published rates for the United States and
      Europe.

PMID- 25077116
TI  - Identifying strategies to improve diabetes care in Alberta, Canada, using the
      knowledge-to-action cycle.
AB  - BACKGROUND: Strategic clinical networks, a recent development in the health
      system in Alberta, have been charged with bringing together front-line
      clinicians, researchers and policy-makers to identify variation in clinical care,
      and to propose standards, pathways and innovative solutions to improve access and
      quality of care. Here, we describe a collaborative workshop held between
      researchers and the Obesity, Diabetes and Nutrition Strategic Clinical Network to
      describe barriers to and facilitators of care for people with diabetes and to
      identify quality improvement interventions that should be prioritized. METHODS:
      Through collaboration between health researchers and the strategic clinical
      network, and using principles of the knowledge-to-action cycle, we identified
      barriers to and facilitators of diabetes care using data from a patient survey
      and a provider focus group (5 primary care physicians and 1 diabetes educator).
      In addition, we identified best evidence from a systematic review of quality
      improvement initiatives in diabetes. This information was reviewed at a
      multistakeholder workshop where potential quality improvement initiatives were
      considered at various service levels. RESULTS: A pilot survey involving 59
      patients with diabetes and a focus group of primary care and allied health care
      providers identified several important barriers to optimal outcomes in diabetes
      care, including patient-level financial barriers to care and difficulty
      navigating the health system. Our collaborative discussion using the knowledge-to
      action cycle prioritized feasible, evidence-based interventions to improve
      outcomes for patients with diabetes, including enabling care by allied health
      care providers and creating clear care maps and processes for system navigation.
      INTERPRETATION: We identified important barriers to achieving optimal outcomes in
      diabetes that may be overcome through the use of evidence-based quality
      improvement interventions. As recommended within the knowledge-to-action cycle,
      future research is required to determine whether program implementation improves
      outcomes and is cost-effective.

PMID- 25077117
TI  - Trends in use and cost of initial cancer treatment in Ontario: a population-based
      descriptive study.
AB  - BACKGROUND: Cancer incidence and treatment-related costs are rising in Canada. We
      estimated health care use and costs in the first year after diagnosis for
      patients with 7 common types of cancer in Ontario to examine temporal trends in
      patterns of care and costs. METHODS: We selected patients aged 19-44 years who
      had received a diagnosis of melanoma, breast cancer (female only), testicular
      cancer or thyroid cancer, in addition to patients aged 45 years and older who had
      received a diagnosis of breast (female only), prostate, lung or colorectal
      cancer, between 1997 and 2007. Patients were identified from the Ontario Cancer
      Registry. Using linked administrative databases, we determined use and costs of
      chemotherapy, radiotherapy, cancer-related surgery, other admissions to hospital
      and home care. We adjusted all costs to 2009 Canadian dollars. RESULTS: We
      identified 20 821 patients aged 19-44 years and 178 797 patients aged 45 years
      and older. The greatest increases in costs during the study period were for
      melanoma, breast cancer, colorectal cancer, lung cancer and prostate cancer (p <
      0.05). For prostate and lung cancers, mean costs increased 50% (from $11 490 and
      $22 037 to $15 170 and $34 473, respectively). Mean costs doubled for breast
      (from $15 460 and $12 909 to $35 977 and $29 362 for younger and older patients,
      respectively) and colorectal cancers (from $24 769 to $43 964), and nearly
      tripled for melanoma (from $3581 to $8934). Costs related to hospital admissions
      accounted for the largest portion of total costs. The use of chemotherapy,
      radiotherapy and home care generally increased for all cancers. INTERPRETATION:
      The significant increase in mean costs of initial cancer treatment among the
      patients included in this study was primarily due to more patients receiving
      adjuvant therapy and home care, and to the increasing expenditures for these
      services and cancer-related surgeries. Understanding trends in health care use
      and costs can help policy-makers to take the necessary measures to achieve a more
      accountable, high-performing health care system.

PMID- 25077118
TI  - Screening for depression: a systematic review and meta-analysis.
AB  - BACKGROUND: The Canadian Task Force on Preventive Health Care has a guideline on
      screening for depression among adults 18 years of age or older at average or high
      risk for depression. To provide evidence for an update of this guideline, we
      evaluated the literature on the effectiveness of screening for depression in
      adults. METHODS: For the period 1994 to May 23, 2012, we searched the following
      electronic databases: MEDLINE, Embase, PsycINFO, the Cochrane Central Register of
      Controlled Trials and the Cochrane Database of Systematic Reviews. Randomized
      controlled trials, observational studies and systematic reviews with evidence for
      the benefits or harms of screening for depression were eligible for inclusion. We
      performed screening for relevance, extraction of data, analysis of risk of bias
      and quality assessments in duplicate. We used the generic inverse variance method
      to conduct a meta-analysis. To determine confidence in the effect, we analyzed
      the results according to the Grading of Recommendations Assessment, Development
      and Evaluation (GRADE) system. RESULTS: Five quasi-experimental studies (before
      after design with a nonrandomized control group) met the inclusion criteria for
      this review. These studies reported on the effect of community-based screening
      for depression, with follow-up on the risk of suicide completion, for older
      residents in regions of rural Japan with high suicide rates. Meta-analysis showed
      that the screening program had a protective effect on the overall incidence of
      suicide completion (ratio of rate ratios [RRR] 0.50, 95% confidence interval
      [CI], 0.32-0.78). When sex was considered, the RRR indicated a significantly
      lower rate of suicide among women (RRR 0.37, 95% CI 0.21-0.66) but not among men
      (RRR 0.67, 95% CI 0.35-1.27). The overall GRADE rating applied to this evidence
      indicated very low quality. No studies addressing the harms of screening for
      depression met the inclusion criteria for the review. INTERPRETATION: There is
      very limited research evidence allowing conclusions about the effectiveness of
      screening for depression in either average-risk or high-risk populations.

PMID- 25077119
TI  - Guideline harmonization and implementation plan for the BETTER trial: Building on
      Existing Tools to Improve Chronic Disease Prevention and Screening in Family
      Practice.
AB  - BACKGROUND: The aim of the Building on Existing Tools to Improve Chronic Disease
      Prevention and Screening in Family Practice (BETTER) randomized controlled trial
      is to improve the primary prevention of and screening for multiple conditions
      (diabetes, cardiovascular disease, cancer) and some of the associated lifestyle
      factors (tobacco use, alcohol overuse, poor nutrition, physical inactivity). In
      this article, we describe how we harmonized the evidence-based clinical practice
      guideline recommendations and patient tools to determine the content for the
      BETTER trial. METHODS: We identified clinical practice guidelines and tools
      through a structured literature search; we included both indexed and grey
      literature. From these guidelines, recommendations were extracted and integrated
      into knowledge products and outcome measures for use in the BETTER trial. End
      users (family physicians, nurse practitioners, nurses and dieticians) were
      engaged in reviewing the recommendations and tools, as well as tailoring the
      content to the needs of the BETTER trial and family practice. RESULTS: In total,
      3-5 high-quality guidelines were identified for each condition; from these, we
      identified high-grade recommendations for the prevention of and screening for
      chronic disease. The guideline recommendations were limited by conflicting
      recommendations, vague wording and different taxonomies for strength of
      recommendation. There was a lack of quality evidence for manoeuvres to improve
      the uptake of guidelines among patients with depression. We developed the BETTER
      clinical algorithms for the implementation plan. Although it was difficult to
      identify high-quality tools, 180 tools of interest were identified.
      INTERPRETATION: The intervention for the BETTER trial was built by integrating
      existing guidelines and tools, and working with end-users throughout the process
      to increase the intervention's utility for practice. TRIAL REGISTRATION:
      ISRCTN07170460.

PMID- 25077120
TI  - Utilization and costs of home care for patients with colorectal cancer: a
      population-based study.
AB  - BACKGROUND: The utilization and costs of home care services provided for people
      with colorectal cancer is not well-known. We conducted an analysis to determine
      the utilization and costs of such services associated with each stage of
      colorectal cancer among patients in the province of Ontario. METHODS: We included
      cases of colorectal cancer diagnosed in Ontario between Jan. 1, 2005, and Dec.
      31, 2009. Data were extracted from the Ontario Cancer Registry and linked to data
      from a home care administrative database. The types of services used were
      stratified by stage of disease and by phase of care (initial phase = 180 d after
      diagnosis, terminal phase = 180 d before death, continuing phase = interval
      between initial and terminal phases). Overall utilization rates and costs were
      determined, and regression analysis was used to examine associated factors.
      RESULTS: A total of 36 195 patients had colorectal cancer diagnosed during the
      study period; the median age was 71 (interquartile range 61-79) years. Home care
      services were provided to 24 641 patients (68.1%). The number of services per
      patient-year was 27.5, at a cost of $2180 per patient-year. The number of
      services provided per patient-year increased with increasing disease severity at
      diagnosis (15.5 at stage I, 25.5 at stage II, 32.5 at stage III and 62.5 at stage
      IV; 22.6 for unstaged disease). The cost of services per patient-year also
      increased with disease severity at diagnosis ($1170 at stage I, $1995 at stage
      II, $2727 at stage III and $5541 at stage IV). Publicly funded home care services
      and associated costs decreased with increasing income group, but they increased
      among patients who had a history of high health resource utilization. The mean 30
      day cost of home care services decreased from the initial phase of care ($323) to
      the continuing phase ($160) but increased during the terminal phase ($616).
      INTERPRETATION: More than two-thirds of the patients with colorectal cancer in
      this study used home care services. Those who received home care services used
      about 2 services per month in a one-year period, at a cost of about $2000 per
      year. This information can aid policy-makers in future decisions regarding
      resource allocations.

PMID- 25077121
TI  - Current and predicted prevalence of obesity in Canada: a trend analysis.
AB  - BACKGROUND: The prevalence of obesity has increased over the past 3 decades, with
      a disproportionate growth in excessive weight categories (body mass index [BMI]
      35.0-39.9 and BMI >= 40.0). The objective of this paper is to present the data
      for the past and current prevalence of adult obesity in Canada, together with
      future estimates. METHODS: We calculated BMIs for adults aged 18 years and older
      who were not in long-term care using data from Canadian health surveys
      administered between 1985 and 2011. Calculation of the BMIs was based on self
      reported heights and weights. The weight categories were as follows: normal (BMI
      18.5-24.9), overweight (25.0-29.9), obese class I (30.0-34.9), obese class II
      (35.0-39.9) and obese class III (>= 40.0). Outcome measures were prevalence of
      adult obesity according to BMI categories, nationally and provincially. We used
      regression analysis models to predict future prevalence of adult obesity up to
      2019. RESULTS: Between 1985 and 2011, the prevalence of adult obesity in Canada
      increased from 6.1% to 18.3%. Furthermore, since 1985, the prevalence of obesity
      in classes I, II and III increased from 5.1% to 13.1%, from 0.8% to 3.6%, and
      from 0.3% to 1.6%, respectively. Taking into account regional variations, we
      predict that, by 2019, the prevalence of obesity in classes I, II and III will
      increase to 14.8%, 4.4% and 2.0%, respectively, and that half of the Canadian
      provinces will have more overweight or obese adults than normal-weight adults.
      INTERPRETATION: We found significant increases in the excessive weight categories
      of obesity, with continued increases predicted for all provinces up to 2019.
      Provincial variations in obesity prevalence were also significant. To address
      these projected increases and any subsequent burden on the health care system, a
      concerted effort must be made by the provinces to focus on the prevention,
      management and treatment of obesity in Canada.

PMID- 25077122
TI  - Access to primary care and other health care use among western Canadians with
      chronic conditions: a population-based survey.
AB  - BACKGROUND: For adults with chronic conditions, access to primary care, including
      multidisciplinary care, is associated with better outcomes. Few studies have
      assessed barriers to such care. We sought to describe barriers to primary care,
      including care from allied health professionals, for adults with chronic
      conditions. METHODS: We surveyed western Canadians aged 40 years or older who had
      hypertension, diabetes, heart disease or stroke about access to primary care and
      other use of health care. Using log binomial regression, we determined the
      association between sociodemographic variables and several indicators of access
      to primary care and care from allied health professionals. RESULTS: Of the 2316
      people who were approached, 1849 (79.8%) completed the survey. Most of the
      respondents (95.1%) had a regular medical doctor, but two-thirds (68.1%) did not
      have after-hours access. Only 6.1% indicated that allied health professionals
      were involved in their care, although most respondents (87.3%) indicated they
      would be willing to see a nurse practitioner if their primary care physician was
      not available. Respondents who were obese or less than 65 years of age were less
      likely to have a regular medical doctor. Individuals who had diabetes, lived in a
      rural area, were residents of Alberta or had poorer health were more likely to
      have allied health professionals involved in their care. INTERPRETATION: The
      survey results identified barriers to accessing primary care for people with
      chronic conditions. Opportunities for improving access to primary care may
      include greater involvement by allied health professionals, such as nurse
      practitioners.

PMID- 25077124
TI  - Geographic and facility-level variation in the use of peritoneal dialysis in
      Canada: a cohort study.
AB  - BACKGROUND: Peritoneal dialysis is associated with similar survival and similar
      improvement in quality of life and is less costly compared with in-centre
      hemodialysis. We examined facility and geographic variation in the use of
      peritoneal dialysis in Canada. METHODS: We analyzed data from the Canadian Organ
      Replacement Register for the period January 2001 to December 2010. We identified
      patients for whom peritoneal dialysis was the primary modality at 90 days after
      initiation of dialysis. We used multilevel models to evaluate variation in use of
      peritoneal dialysis by facility and geographic region. RESULTS: We analyzed data
      for 31 778 incident dialysis patients at 56 facilities in 13 geographic regions
      across Canada. Use of peritoneal dialysis at 90 days varied considerably across
      geographic regions (range 19.8%-36.1%) and declined over time, from 28.8% in 2001
      to 22.5% in 2010. After adjustment for case mix and facility-level quality
      indicators, 9.3% and 3.4% of the variability was attributable to facility and
      geographic factors, respectively. In adjusted models, there was a substantial
      difference between geographic regions with the lowest and highest peritoneal
      dialysis use (odds ratio for high use 1.51, 95% confidence interval [CI] 1.33
      1.73 v. odds ratio for low use 0.69, 95% CI 0.60-0.79). INTERPRETATION: In
      Canada, substantial variability in the use of peritoneal dialysis attributable to
      facility and geographic region was not explained by differences in patient case
      mix. An opportunity exists to optimize use of this cost-effective therapy through
      changes in policy and standardization of criteria for initiation of peritoneal
      dialysis.

PMID- 25077125
TI  - Rates of breast cancer surgery in Canada from 2007/08 to 2009/10: retrospective
      cohort study.
AB  - BACKGROUND: Surgery is a common and important component of breast cancer
      treatment. We assessed the rates of breast cancer surgery across Canada from
      2007/08 to 2009/10. METHODS: We used hospital and day surgery data from the
      Canadian Institute for Health Information to assemble a cohort of women who had
      undergone breast cancer surgery. We identified the index surgical procedure and
      subsequent surgical procedures performed within 1 year for each woman included in
      the analysis. We calculated the crude mastectomy rate for each province, and we
      calculated the adjusted mastectomy rate for select jurisdictions using a logistic
      regression model fitted using age, neighbourhood income quintile and travel time.
      RESULTS: In total, 57 840 women underwent breast cancer surgery during the study
      period. Among women with unilateral invasive breast cancer, the crude mastectomy
      rate was 39%. Adjusted rates for mastectomy varied widely by province (26%-69%).
      The rate of re-excision within 1 year for women who had breast-conserving surgery
      as their index procedure was 23% and varied by province in terms of frequency and
      type (mastectomy or repeat breast-conserving surgery). Among women who underwent
      mastectomy for unilateral invasive breast cancer, 6% also underwent contralateral
      prophylactic mastectomy, and 7% had immediate breast reconstruction following
      surgery. Of mastectomy procedures, 20% were performed as day surgery; for breast
      conserving surgery, 70% were performed as day surgery. INTERPRETATION: There is
      substantial interprovincial variation in surgical care for breast cancer in
      Canada. Further research is needed to better understand such variation, and
      continued monitoring should be the focus of quality initiatives.

PMID- 25077126
TI  - Trends in infection-related hospital admissions and impact of length of time on
      dialysis among patients on long-term dialysis: a retrospective cohort study.
AB  - BACKGROUND: After cardiovascular disease, infection is the second leading reason
      for admission to hospital among patients receiving long-term dialysis. We
      examined whether duration of dialysis treatment influences the rate of infection
      related admission to hospital. METHODS: Using provincial administrative databases
      for Quebec, we built a retrospective cohort of all adults receiving long-term
      dialysis (hemodialysis or peritoneal dialysis) between 2001 and 2007. We
      evaluated rates of infection-related admission to hospital according to length of
      time on dialysis. RESULTS: A cohort of 9822 patients (mean age 66.3 [standard
      deviation +/- 14.7] yr; 39.7% female) were followed for a median of 2.1 (range
      1.0-3.9) years. Between 2001 and 2007, infection-related hospital admissions
      remained stable (from 0.20 to 0.19 per person-year; p = 0.7). All-cause hospital
      admission rates decreased by 22.9% (from 1.53 to 1.18 per person-year; p <
      0.001), and cardiovascular-related admission rates decreased by 46.7% (from 0.45
      to 0.24 per person-year; p < 0.001). The rate of infection-related admission
      remained stable with increasing time on dialysis (p = 0.1); however, both all
      cause and cardiovascular-related admission rates decreased with length of time on
      dialysis (p < 0.001). Standardization of hospital admission rates by age, sex or
      length of time on dialysis did not change trends. INTERPRETATION: We found a
      stable rate of infection-related hospital admission between 2001 and 2007 among
      patients on long-term dialysis, independent of age, sex and length of time on
      dialysis. A decrease in all-cause and cardiovascular-related admission rates
      during the same period meant that the proportion of admissions related to
      infection increased. Because admissions to hospital are potentially preventable,
      understanding the epidemiology of infection-related admissions may inform future
      studies on prevention of this serious outcome.

PMID- 25077127
TI  - Understanding the effect of resident duty hour reform: a qualitative study.
AB  - BACKGROUND: Concern surrounding the effect of resident fatigue on patient care
      recently led the National Steering Committee on Resident Duty Hours to publish
      Canadian recommendations suggesting that duty periods of 24 or more consecutive
      hours without restorative sleep should be avoided. We sought to characterize how
      different training programs are preparing for the effect of such changes on
      education, patient care and provider well-being. METHODS: Using constructivist
      grounded theory methodology, we conducted 18 one-on-one semistructured interviews
      with program directors, division directors and department chiefs from 11
      residency programs affiliated with one Canadian medical school. We gathered and
      analyzed data iteratively until we reached theoretical saturation. RESULTS: The
      key theme articulated by our participants was that changes in resident duty hours
      would potentially lead to gaps in the provision of clinical care. These changes
      affect acute care specialties based primarily in the inpatient setting (e.g.,
      medicine, surgery) more than primarily ambulatory (e.g., family medicine) or
      shift-model based (e.g., emergency) specialties. Potential strategies to address
      gaps in clinical care include resident-based solutions, faculty-based solutions
      and solutions based on other providers (e.g., nonacademic physicians, physician
      extenders). Each solution has unique advantages and disadvantages in terms of
      education, continuity of care, preparedness for practice and provider well-being.
      INTERPRETATION: Our data-driven framework serves as a guide for programs to
      anticipate challenges of satisfying clinical care needs in the face of changes to
      resident duty hours, while balancing education, care continuity, preparedness for
      practice and provider well-being. Our findings challenge the "one-size-fits-all"
      approach to changes to resident duty hours and endorse flexibility in enacting
      duty hour regulations based on specialty-specific factors.

PMID- 25077128
TI  - Incidence of prenatal alcohol exposure in Prince Edward Island: a population
      based descriptive study.
AB  - BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a leading preventable cause
      of neurodevelopmental disability in North America. The stigma associated with
      alcohol use and abuse during pregnancy makes it difficult to obtain information
      on prenatal alcohol use through self-reporting. We assessed the incidence of
      prenatal alcohol exposure in Prince Edward Island to facilitate future public
      health initiatives addressing FASD. METHODS: Prenatal alcohol exposure was
      examined via population-based collection of meconium and analysis of fatty acid
      ethyl esters (FAEEs). Fatty acid ethyl esters are nonoxidative metabolites of
      ethanol that are produced in the fetus. Meconium FAEE concentrations of 2.0
      nmol/g or greater are indicative of frequent prenatal alcohol exposure during the
      last 2 trimesters of pregnancy. Samples were collected from 1307 neonates between
      Nov. 8, 2010, and Nov. 8, 2011, in hospitals in PEI, or from those born to
      mothers who resided in PEI but gave birth in Halifax, Nova Scotia. Samples were
      frozen and shipped for analysis. Fatty acid ethyl esters were analyzed by gas
      chromatography-mass spectrometry and quantified by means of deuterated internal
      standards. RESULTS: Of the 1307 samples collected, 1271 samples were successfully
      analyzed. Positive results for FAEEs were obtained in 3.1% (n = 39) of samples
      collected within the first 24 hours after birth. INTERPRETATION: Not all neonates
      exposed to heavy prenatal alcohol in utero will exhibit FASD; based on current
      estimates of predictive value for disease by exposure, our findings suggest that
      1.3% of neonates born in PEI during this 1-year period will have FASD. In its
      application to an entire provincial birth cohort, this study successfully
      implemented a public health-centred approach for evaluating population-based risk
      of FASD, with implications for practice across Canada.

PMID- 25077129
TI  - Impact of a change in physician reimbursement on bone mineral density testing in
      Ontario, Canada: a population-based study.
AB  - BACKGROUND: On Apr. 1, 2008, a revision was made to the fee schedule for bone
      mineral density testing with dual-energy x-ray absorptiometry (DXA) in the
      province of Ontario, Canada, reducing the frequency of repeat screening in
      individuals at low risk of osteoporosis. We evaluated whether the change in
      physician reimbursement successfully promoted appropriate bone mineral density
      testing, with reduced use among women at low risk and increased use among women
      and men at higher risk of osteoporosis-related fracture. METHODS: We analyzed
      data from administrative databases on physician billings, hospital discharges and
      emergency department visits. We included all physician claims for DXA in the
      province to assess patterns in bone mineral density testing from Apr. 1, 2002, to
      Mar. 31, 2011. People at risk of an osteoporosis-related fracture were defined as
      women and men aged 65 years or more and those who had a recent (< 6 mo) fracture
      after age 40 years. Joinpoint regression analysis was used to examine trends in
      DXA testing. RESULTS: Before the policy change, the overall number of DXA tests
      increased from 433 419 in 2002/03 to 507 658 in 2007/08; after revision of the
      fee schedule, the number decreased to 422 915 by 2010/11. Most of this reduction
      was due to a decrease in the age-standardized rate of DXA testing among women
      deemed to be at low risk, from 5.7 per 100 population in 2008/09 to 1.8 per 100
      in 2010/11. In the high-risk group of people aged 65 or more, the age
      standardized rate of testing increased after the policy change among men but
      decreased among women. Among those at high risk because of a recent clinical
      fracture, the age-standardized rate of DXA testing increased for both sexes and
      then decreased after the policy change. INTERPRETATION: A change in reimbursement
      designed to restrict access to bone mineral density testing among low-risk women
      was associated with an overall reduction in testing. Efforts to communicate
      guidelines for bone mineral density testing with greater clarity, particularly as
      they relate to high-risk individuals, need to be explored.

PMID- 25077130
TI  - Capacity and willingness of patients with chronic noncommunicable diseases to use
      information technology to help manage their condition: a cross-sectional study.
AB  - BACKGROUND: Health care providers have shown considerable interest in using
      information technologies such as email, text messages and video conferencing to
      facilitate the management of chronic noncommunicable diseases such as
      hypertension, diabetes mellitus and vascular disease. We sought to determine
      whether these technologies are available and appealing to the target population.
      METHODS: We analyzed cross-sectional data from a computer-assisted telephone
      survey, conducted by Statistics Canada in February and March 2012, of western
      Canadian adults with at least 1 chronic condition. Survey respondents were asked
      about their capacity (e.g., "Do you own a mobile phone?") and willingness to use
      each of 3 information technologies (email, text messages and video conferencing)
      to interact with health care providers. For all analyses, Statistics Canada's
      calibrated design weights and bootstrap weights were used to obtain population
      level point estimates for proportions and odds ratios. RESULTS: In total, 1849
      (79.8%) of 2316 eligible people participated. Of the 1849 participants, 81.9% had
      hypertension, 26.2% had diabetes, 21.4% had heart disease, and 7.9% had stroke;
      32.2% had more than 1 of the 4 chronic conditions of interest. High proportions
      of respondents owned a computer with Internet access (76.4%, 95% confidence
      interval [CI] 73.3%-79.3%) or a mobile phone (73.9%, 95% CI 70.7%-76.8%). About
      two-thirds of respondents were interested in using email to interact with a
      specialist (66.3%, 95% CI 63.0%-69.5%); respondents were less enthusiastic about
      using text messages (44.9%, 95% CI 41.2%-48.7%). Enthusiasm for video
      conferencing was more pronounced among those residing further from medical
      specialists than among those living closer. Among respondents who were
      potentially interested in video conferencing, almost 50% of remote dwellers would
      use this technology if it saved more than 60 minutes of travel time.
      INTERPRETATION: Many people were interested in using electronic technologies,
      especially video conferencing and email-based methods, to help manage their
      chronic condition. The effectiveness and cost implications of using email and
      video conferencing in the management of chronic disease deserve further
      consideration.

PMID- 25077131
TI  - Active surveillance for low-risk prostate cancer compared with immediate
      treatment: a Canadian cost comparison.
AB  - BACKGROUND: Clinical consequences of active surveillance compared with immediate
      treatment have been evaluated in patients with low-risk prostate cancer; yet, its
      financial benefits have not been adequately studied in Canada or elsewhere. Our
      study objective was to evaluate the direct costs associated with active
      surveillance and immediate treatment in the Canadian context. METHODS: We
      developed a Markov model with Monte Carlo microsimulations to estimate the
      Canadian cost of prostate cancer associated with immediate treatment and active
      surveillance strategies. The patients receiving active surveillance were assumed
      to receive delayed treatment at a rate of 8.35%, 4.17% and 2.1% per year for the
      first 2 years, years 3 to 5, and years 6 to 10 of follow-up, respectively. All
      costs were assigned in Canadian dollars and reflect Quebec's health system.
      RESULTS: With active surveillance, the mean cost of prostate cancer management
      over the first year and 5 years of follow-up was estimated at $6200 (95%
      confidence interval [CI] $6083-$6317) per patient. The mean cost corresponding to
      immediate treatment was estimated at $13 735 (95% CI $13 615-$13 855) per
      patient. We estimated that patients receiving active surveillance who received
      delayed treatment incurred higher costs of $16 257 per patient. INTERPRETATION:
      Active surveillance could offer important economic benefits to the Canadian
      health system, estimated at $96.1 million for each annual cohort of incident
      prostate cancer. These results add to the economic rationale advocating active
      surveillance for eligible men with low-risk prostate cancer.

PMID- 25077132
TI  - Traumatic brain injury among men in an urban homeless shelter: observational
      study of rates and mechanisms of injury.
AB  - BACKGROUND: Little empiric research has investigated the interrelationship
      between homelessness and traumatic brain injury. The objectives of this study
      were to determine the rate, mechanisms and associated outcomes of traumatic brain
      injury among men in an urban homeless shelter. METHODS: We recruited participants
      from an urban men's shelter in Toronto, Ontario. Researchers administered the
      Brain Injury Screening Questionnaire, a semistructured interview screening tool
      for brain injury. Demographic information and detailed histories of brain
      injuries were obtained. Participants with positive and negative screening results
      were compared, and the rates and mechanisms of injury were analyzed by age group.
      RESULTS: A total of 111 men (mean age 54.2 +/- standard deviation 11.5 yr; range
      27-81 yr) participated. Nearly half (50 [45%]) of the respondents had a positive
      screening result for traumatic brain injury. Of these, 73% (35/48) reported
      experiencing their first injury before adulthood (< 18 yr), and 87% (40/46)
      reported a first injury before the onset of homelessness. Among those with a
      positive screening result, 33 (66%) reported sustaining at least one traumatic
      brain injury by assault, 22 (44%) by sports or another recreational activity, 21
      (42%) by motor vehicle collision and 21 (42%) by a fall. A positive screening
      result was significantly associated with a lifetime history of arrest or mental
      illness and a parental history of substance abuse. INTERPRETATION: Multiple
      mechanisms contributed to high rates of traumatic brain injury within a sample of
      homeless men. Assault was the most common mechanism, with sports and recreation,
      motor vehicle collisions and falls also being reported frequently by the
      participants. Injury commonly predated the onset of homelessness, with most
      participants experiencing their first injury in childhood. Additional research is
      needed to understand the complex interactions among homelessness, traumatic brain
      injury, mental illness and substance use.

PMID- 25077133
TI  - Site of hospital readmission and mortality: a population-based retrospective
      cohort study.
AB  - BACKGROUND: Unplanned hospital readmission is a complex process, particularly if
      the patient is readmitted to an acute care institution other than the original
      hospital. This study tested the hypothesis that readmission to an alternative
      hospital is associated with increased mortality compared with readmission to the
      original hospital. METHODS: We performed a population-based retrospective cohort
      analysis set between 1995 and 2010 for all 21 acute care adult general hospitals
      in the Greater Toronto and Hamilton Area. Participants were consecutive adults
      (age >= 18 yr) readmitted through the emergency department within 30 days after
      hospital discharge. The primary outcome measure was all-cause mortality within 30
      days after readmission. RESULTS: Of the 198 149 patients included in the study,
      38 134 (19.2%) died within 30 days after readmission. Patients readmitted to an
      alternative hospital were more likely than those readmitted to the original
      hospital to be older, reside in a chronic-care facility and arrive by ambulance.
      Alternative-hospital readmission was associated with a higher risk of death
      within 30 days (22.3% v. 18.6%, p < 0.001; odds ratio [OR] 1.26, 95% confidence
      interval [CI] 1.23-1.30). The increased risk was substantially less after
      adjustment for patient- and hospital-level covariables (adjusted OR 1.06, 95% CI
      1.02-1.10). Unadjusted Kaplan-Meier survival curves separated early and the
      absolute difference in mortality continued throughout the entire 1-year follow-up
      period, but no difference between groups was observed based on adjusted survival
      analyses. INTERPRETATION: Among patients readmitted within 30 days after
      discharge, readmission to an alternative hospital was associated with a higher
      risk of death than readmission to the original hospital. Whether this adverse
      prognosis reflects a true causal relation or residual confounding is unknown.

PMID- 25077134
TI  - Incidence of invasive aspergillosis following remission-induction chemotherapy
      for acute leukemia: a retrospective cohort study in a single Canadian tertiary
      care centre.
AB  - BACKGROUND: The decision to use universal primary antimould prophylaxis to
      prevent invasive aspergillosis in patients with acute leukemia depends on the
      incidence of infection at individual centres. We determined our institution's
      incidence of invasive aspergillosis among patients who received remission
      induction chemotherapy for acute leukemia to evaluate the potential benefits of
      primary antimould prophylaxis. METHODS: We conducted this retrospective cohort
      study at a Canadian tertiary care centre. From the central pharmacy registries,
      we retrieved records for all adult patients for whom remission-induction
      chemotherapy for acute leukemia was prescribed between 2008 and 2010. We
      retrieved clinical, microbiologic, pathologic and radiologic data from the
      patients' medical charts. The primary outcome was a diagnosis of probable or
      proven invasive aspergillosis up to 180 days after resolution of aplasia.
      RESULTS: We retrieved records for 123 patients with acute leukemia. Twenty-two of
      these patients did not receive the prescribed chemotherapy and were excluded from
      the analysis. Of the 101 patients included, 77 (76.2%) had acute myeloid
      leukemia. Overall, 136 courses of chemotherapy were administered, with more than
      1 course administered to 26 (25.7%) of the 101 patients. In 9 of the patients
      (8.9%; 95% confidence interval 4.2%-16.2%), invasive aspergillosis was diagnosed
      (3 proven and 6 probable cases) a median of 19 (range 11-34) days after
      initiation of chemotherapy. In 7 (78%) of these 9 patients, invasive
      aspergillosis occurred during the first course of chemotherapy. Three patients
      died within the first year after diagnosis of invasive aspergillosis.
      INTERPRETATION: We found a high incidence (8.9%) of invasive aspergillosis at our
      centre. This finding triggered the introduction of targeted antimould prophylaxis
      for patients with acute leukemia who were undergoing remission-induction
      chemotherapy.

PMID- 25077135
TI  - Projections of preventable risks for cardiovascular disease in Canada to 2021: a
      microsimulation modelling approach.
AB  - BACKGROUND: Reductions in preventable risks associated with cardiovascular
      disease have contributed to a steady decrease in its incidence over the past 50
      years in most developed countries. However, it is unclear whether this trend will
      continue. Our objective was to examine future risk by projecting trends in
      preventable risk factors in Canada to 2021. METHODS: We created a population
      based microsimulation model using national data on births, deaths and migration;
      socioeconomic data; cardiovascular disease risk factors; and algorithms for
      changes in these risk factors (based on sociodemographic characteristics and
      previous cardiovascular disease risk). An initial population of 22.5 million
      people, representing the Canadian adult population in 2001, had 13
      characteristics including the risk factors used in clinical risk prediction.
      There were 6.1 million potential exposure profiles for each person each year.
      Outcome measures included annual prevalence of risk factors (smoking, obesity,
      diabetes, hypertension and lipid levels) and of co-occurring risks. RESULTS: From
      2003 to 2009, the projected risks of cardiovascular disease based on the
      microsimulation model closely approximated those based on national surveys.
      Except for obesity and diabetes, all risk factors were projected to decrease
      through to 2021. The largest projected decreases were for the prevalence of
      smoking (from 25.7% in 2001 to 17.7% in 2021) and uncontrolled hypertension (from
      16.1% to 10.8%). Between 2015 and 2017, obesity was projected to surpass smoking
      as the most prevalent risk factor. INTERPRETATION: Risks of cardiovascular
      disease are projected to decrease modestly in Canada, leading to a likely
      continuing decline in its incidence.

PMID- 25077136
TI  - The Irrationality of GOF Avian Influenza Virus Research.
AB  - The last two and a half years have witnessed a curious debate in virology
      characterized by a remarkable lack of discussion. It goes by the misleading
      epithet "gain of function" (GOF) influenza virus research, or simply GOF. As will
      be seen, there is nothing good to be gained. The controversial experiments confer
      aerosol transmission on avian influenza virus strains that can infect humans, but
      which are not naturally transmitted between humans. Some of the newer strains are
      clearly highly pathogenic for man. It will be shown here that the benefits of the
      work are erroneous and overstated while the risk of an accident is finite, if
      small. The consequence of any accident would be anywhere from a handful of
      infections to a catastrophic pandemic. There has been a single open international
      meeting in this period, which is surprising given that openness and discussion
      are essential to good science. Despite US and EU government funding, no risk
      benefit analysis has been published, which again is surprising. This research can
      be duplicated readily in many labs and requires little high tech. It falls under
      the definition of DURC without the slightest shadow of a doubt and constitutes
      the most important challenge facing contemporary biology. 

PMID- 25077138
TI  - Assessing the quality of teleconsultations in a store-and-forward telemedicine
      network.
AB  - Store-and-forward telemedicine in resource-limited settings is becoming a
      relatively mature activity. However, there are few published reports about
      quality measurement in telemedicine, except in image-based specialties, and they
      mainly relate to high- and middle-income countries. In 2010, Medecins Sans
      Frontieres (MSF) began to use a store-and-forward telemedicine network to assist
      its field staff in obtaining specialist advice. To date, more than 1000 cases
      have been managed with the support of telemedicine, from a total of 40 different
      countries. We propose a method for assessing the overall quality of the
      teleconsultations provided in a store-and-forward telemedicine network. The
      assessment is performed at regular intervals by a panel of observers, who -
      independently - respond to a questionnaire relating to a randomly chosen past
      case. The answers to the questionnaire allow two different dimensions of quality
      to be assessed: the quality of the process itself and the outcome, defined as the
      value of the response to three of the four parties concerned, i.e., the patient,
      the referring doctor, and the organization. It is not practicable to estimate the
      value to society by this technique. The feasibility of the method was
      demonstrated by using it in the MSF telemedicine network, where process quality
      scores, and user-value scores, appeared to be stable over a 9-month trial period.
      This was confirmed by plotting the cusum of a portmanteau statistic (the sum of
      the four scores) over the study period. The proposed quality-assessment method
      appears feasible in practice, and will form one element of a quality assurance
      program for MSF's telemedicine network in future. The method is a generally
      applicable one, which can be used in many forms of medical interaction. 

PMID- 25077137
TI  - HIV-Infected Individuals Who Delay, Decline, or Discontinue Antiretroviral
      Therapy: Comparing Clinic- and Peer-Recruited Cohorts.
AB  - A substantial proportion of persons living with HIV/AIDS (PLHA) delay, decline,
      or discontinue antiretroviral therapy (ART) when it is medically indicated (40
      45%), largely African-Americans and Latinos/Hispanics. This study explores the
      feasibility of locating PLHA, who are not on ART (PLHA-NOA) through clinics and
      peer-referral; compares the two cohorts on multi-level barriers to ART; and
      examines readiness to initiate/reinitiate ART, a predictor of treatment outcomes.
      We recruited adult HIV-infected African-American and Latino/Hispanic PLHA-NOA
      through HIV hospital clinics and peer-referral in 2012-2013. Participants were
      engaged in structured 1-h assessments with reliable/valid measures on barriers to
      ART. We found that recruitment through peers (63.2%, 60/95) was more feasible
      than in clinics (36.8%, 35/90). Participants were 48.0 years old and had lived
      with HIV for 14.7 years on average, and 56.8% had taken ART previously. Most
      (61.1%) were male and African-American (76.8%), and 23.2% were Latino/Hispanic.
      Peer-recruited participants were older, had lived with HIV longer, were less
      engaged in HIV care, and were more likely to have taken ART previously. The
      cohorts differed in reasons for discontinuing ART. Levels of ART knowledge were
      comparable between cohorts (68.5% correct), and there were no differences in
      attitudes toward ART (e.g., mistrust), which were in the neutral range. In
      bivariate linear regression, readiness for ART was negatively associated with
      physician mistrust (B = -10.4) and positively associated with self-efficacy (B =
      5.5), positive outcome expectancies (B = 6.3), beliefs about personal necessity
      of ART (B = 17.5), and positive internal norms (B = 7.9). This study demonstrates
      the feasibility of engaging this vulnerable population through peer-referral.
      Peer-recruited PLHA evidence particularly high rates of risk factors compared to
      those in hospital clinics. Interventions to support ART initiation and
      continuation are sorely needed for both subgroups. 

PMID- 25077139
TI  - Healthcare for persons with intellectual and developmental disability in the
      community.
AB  - INTRODUCTION: While there has been impressive progress in creating and improving
      community healthcare delivery systems that support people with intellectual and
      developmental disabilities (IDD), there is much more that can and should be done.
      METHODS: This paper offers a review of healthcare delivery concepts on which new
      models are being developed, while also establishing an historical context. We
      review the need for creating fully integrated models of healthcare, and at the
      same time offer practical considerations that range from specific healthcare
      delivery system components to the need to expand our approach to training
      healthcare providers. The models and delivery systems, and the areas of needed
      focus in their development are reviewed to set a starting point for more and
      greater work going forward. CONCLUSION: Today, we celebrate longer life spans of
      people with IDD, increased attention to the benefits of healthcare that is
      responsive to their needs, and the development of important healthcare delivery
      systems that are customized to their needs. We also know that the growing body of
      research on health status offers incentive to continue developing healthcare
      structures for people with IDD by training healthcare providers about the needs
      of people with IDD, by establishing systems of care that integrate acute
      healthcare with long-term services and support, by developing IDD medicine as a
      specialty, and by building health promotion and wellness resources to provide
      people with IDD a set of preventative health supports.

PMID- 25077140
TI  - Frontiers and challenges in occupational safety and health.

PMID- 25077143
TI  - Microsolvation of molecules in superfluid helium nanodroplets revealed by means
      of electronic spectroscopy.
AB  - The empirical model explaining microsolvation of molecules in superfluid helium
      droplets proposes a non-superfluid helium solvation layer enclosing the dopant
      molecule. This model warrants an empirical explanation of any helium induced
      substructure resolved for electronic transitions of molecules in helium droplets.
      Despite a wealth of such experimental data, quantitative modeling of spectra is
      still in its infancy. The theoretical treatment of such many-particle systems
      dissolved into a quantum fluid is a challenge. Moreover, the success of
      theoretical activities relies also on the accuracy and self-critical
      communication of experimental data. This will be elucidated by a critical resume
      of our own experimental work done within the last ten years. We come to the
      conclusion that spectroscopic data and among others in particular the spectral
      resolution depend strongly on experimental conditions. Moreover, despite the fact
      that none of the helium induced fine structure speaks against the empirical model
      for solvation in helium droplets, in many cases an unequivocal assignment of the
      spectroscopic details is not possible. This ambiguity needs to be considered and
      a careful and critical communication of experimental results is essential in
      order to promote success in quantitatively understanding microsolvation in
      superfluid helium nanodroplets. 

PMID- 25077141
TI  - Development of organophosphate hydrolase activity in a bacterial homolog of human
      cholinesterase.
AB  - We applied a combination of rational design and directed evolution (DE) to
      Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing
      organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a
      designed variant, pNBE A107H, carrying a histidine homologous with human
      butyrylcholinesterase G117H to find complementary mutations that further enhance
      its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400)
      within a 6.7 A radius of the nucleophilic serine Ogamma. All 95 variants were
      screened for esterase activity with a set of five substrates: pNP-acetate, pNP
      butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A
      microscale assay for OPAAH activity was developed for screening DE libraries.
      Reductions in esterase activity were generally concomitant with enhancements in
      OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its k
      cat/K m for benzoylthiocholine, demonstrating that it is also possible to enhance
      the cholinesterase activity of pNBE. Moreover, DE resulted in at least three
      variants with modestly enhanced OPAAH activity compared to wild type pNBE.
      A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a
      slow time- and temperature-dependent change affecting the hydrolysis of OPAA and
      ester substrates. Structural analysis suggests that pNBE may represent a
      precursor leading to human cholinesterase and carboxylesterase 1 through
      extension of two vestigial specificity loops; a preliminary attempt to transfer
      the Omega-loop of BChE into pNBE is described. Unlike butyrylcholinesterase and
      pNBE, introducing a G143H mutation (equivalent to G117H) did not confer
      detectable OP hydrolase activity on human carboxylesterase 1 (hCE1). We discuss
      the use of pNBE as a surrogate scaffold for the mammalian esterases, and the
      importance of the oxyanion-hole residues for enhancing the OPAAH activity of
      selected serine hydrolases. 

PMID- 25077144
TI  - Medical training for communication of bad news: A literature review.
AB  - In recent years, medical guidelines for communicating bad news to patients have
      been published. Training for this task was included in the curricula of
      undergraduate medical courses, specialization, and continuing medical education.
      The objective of this review is to evaluate the existing evidence in the
      literature on the effectiveness of such training. Only seven controlled trials
      were found, four of which were randomized, and these four indicate an improvement
      in the trainees. These findings suggest that training undergraduate and
      postgraduate doctors in skills for communicating bad news may be beneficial but
      there are important limitations to reach a definitive conclusion. These
      limitations are discussed in this article. 

PMID- 25077145
TI  - Analysis of databases appropriation in the academic staffs of Iranian
      Universities of Medical Sciences according to the social appropriation approach.
AB  - BACKGROUND: Numerous researches conducted on about the quality of perception of
      media messages shows that the people are not passive receivers but they have the
      ability of understanding, interpreting and accepting or rejecting messages. In
      order to make clear the relationship of information and communication
      technologies with social changes and to gain a broader vision from this scope,
      sociological theories about information and communication technologies' usage,
      especially appropriation approach can be very useful. So, keeping in mind the
      important role of Databases in the qualitative expansion of education, research,
      diagnosis, remedy and medical services presentation, this research was carried
      out with the aim of status determination of databases appropriation in the
      academic staffs of Iranian Universities of Medical Sciences according to the
      social appropriation approach in 2012. MATERIALS AND METHODS: This is an
      applicative research of an analytical-descriptive type, which was carried out by
      measurement approach. The statistical society of this research was composed of
      the academic staffs of the Iranian Universities of Medical Sciences in 2012 and
      finally 390 academic staffs were selected according to the Cochran's formula were
      selected. The research tool are searcher's made questionnaire, which was composed
      of nine separate parts. Its validity was accepted by the specialists and its
      reliability was calculated and found to be 0.961 by Cronbakh's alpha. RESULTS:
      Database appropriation score in the academic staffs of Iranian Universities of
      Medical Sciences with 65.020% was in a good status and data bases dis
      appropriation score with 71.484 was in a high status. CONCLUSION: According to
      the findings of this research, Librarians and politicians in this scope-with
      determination of the academic staff's positive and negative points in usage and
      appropriation would be capable of accurately diagnozing and analyzing the chances
      and challenges of the academic staffs members in using databases and would also
      be capable of achieving solutions and appropriate catalyzers of prolific usage
      and appropriation of databases.

PMID- 25077146
TI  - The efficacy of hepatitis B vaccine in Iranian population: A systematic review
      and meta-analysis.
AB  - INTRODUCTION: Hepatitis B infection is an important health problem all over the
      world, and according to the studies, Iran is a country with intermediate
      prevalence, so vaccination is a cost-benefit approach. In this study, evidence
      about the efficacy of hepatitis B vaccine was collected by systematic review
      methods and its amount was estimated by a meta-analysis. MATERIALS AND METHODS:
      In this study, documents and literature search were performed using valid key
      words in Information Sciences Institute, PubMed, Scientific Information Data
      base, and Iranmedex databases from 1997 to 2010 in different regions of Iran. All
      cross-sectional studies about the efficacy of hepatitis B vaccine in Iran which
      fulfilled the inclusion criteria entered the study. Antibody titer (Anti
      hemoglobins > 10 IU/L) was considered as the desired efficacy. In order to
      present the results, prevalence and Forest plot were used and for evaluation of
      the inconsistency meta-regression model and I(2) index were used. We used
      R.15.3.2 software for analysis. RESULTS: Totally 64 studies (52 studies in
      general population and 12 studies among specific populations) including 12,575
      subjects with age range from 8 months to 55 years entered the meta-analysis. The
      efficacy was 86.3% (confidence interval [CI]: 83.9-88.7%) in the general
      population and 59.62% (CI: 47.9-71.29%) in specific patient populations. Also the
      efficacy was significantly related to the year of publication, age and gender (P
      < 0.05). CONCLUSION: Prevention is an important issue in general health.
      Hepatitis B vaccination is one of the methods used to prevent hepatitis B
      infection. According to this study, the efficacy of hepatitis B vaccination was
      more than 80% in general population, so injection of full course of hepatitis B
      vaccinationis enough and booster dose is not required.

PMID- 25077147
TI  - Evaluation of organizational maturity based on people capacity maturity model in
      medical record wards of Iranian hospitals.
AB  - CONTEXT: People capacity maturity model (PCMM) is one of the models which focus
      on improving organizational human capabilities. AIMS: The aim of this model's
      application is to increase people ability to attract, develop, motivate, organize
      and retain the talents needed to organizational continuous improvement. SETTINGS
      AND DESIGN: In this study, we used the PCMM for investigation of organizational
      maturity level in medical record departments of governmental hospitals and
      determination strengths and weaknesses of their staff capabilities. MATERIALS AND
      METHODS: This is an applied research and cross sectional study in which data were
      collected by questionnaires to investigation of PCMM model needs in medical
      record staff of governmental hospitals at Isfahan, Iran. We used the
      questionnaire which has been extracted from PCMM model and approved its
      reliability with Cronbach's Alpha 0.96. STATISTICAL ANALYSIS USED: Data collected
      by the questionnaire was analyzed based on the research objectives using SPSS
      software and in accordance with research questions descriptive statistics were
      used. RESULTS: Our findings showed that the mean score of medical record
      practitioners, skill and capability in governmental hospitals was 35 (62.5%) from
      maximum 56 (100%). There is no significant relevance between organizational
      maturity and medical record practitioners, attributes. CONCLUSIONS: Applying PCMM
      model is caused increasing staff and manager attention in identifying the
      weaknesses in the current activities and practices, so it will result in
      improvement and developing processes.

PMID- 25077142
TI  - Revisiting 30 years of biofunctionalization and surface chemistry of inorganic
      nanoparticles for nanomedicine.
AB  - In the last 30 years we have assisted to a massive advance of nanomaterials in
      material science. Nanomaterials and structures, in addition to their small size,
      have properties that differ from those of larger bulk materials, making them
      ideal for a host of novel applications. The spread of nanotechnology in the last
      years has been due to the improvement of synthesis and characterization methods
      on the nanoscale, a field rich in new physical phenomena and synthetic
      opportunities. In fact, the development of functional nanoparticles has
      progressed exponentially over the past two decades. This work aims to extensively
      review 30 years of different strategies of surface modification and
      functionalization of noble metal (gold) nanoparticles, magnetic nanocrystals and
      semiconductor nanoparticles, such as quantum dots. The aim of this review is not
      only to provide in-depth insights into the different biofunctionalization and
      characterization methods, but also to give an overview of possibilities and
      limitations of the available nanoparticles. 

PMID- 25077148
TI  - Study of the relationship between the aerobic capacity (VO2 max) and the rating
      of perceived exertion based on the measurement of heart beat in the metal
      industries Esfahan.
AB  - BACKGROUND AND OBJECTIVE: To establish a balance between work (physical exercise)
      and human beings, the aerobic capacity (VO2 max) could be used as a measure.
      Additionally, the subjective and physiological assessment could be applied as one
      of the methods for assessing physical exercise. The most commonly used tools for
      the assessment of fatigue during physical exercise include the Borg scale Rating
      of perceived Exertion (RPE) in relation to subjective symptoms and heart rate
      (HR) in relation to physiological symptoms. The study is aimed to investigate the
      relationship between the aerobic capacity and the RPE based on the measurement of
      heat rate (HR) of workers from the Metal Industries of Isfahan. MATERIALS AND
      METHODS: The subjects were 200 male workers from metal components manufacturers
      in Isfahan selected by using random sampling based on statistic method. The
      subjects were examined by using ergometer in accordance with A strand 6 minutes
      cycle test protocol. Furthermore, the subjects were asked to rate their status
      based on the Borg rating scale at the end of each minute. Additionally, their
      heat rates were monitored and recorded automatically at the end of each minutes.
      RESULTS: Statistical analysis showed that there was a significant relationship
      between the RPE and the aerobic capacity (VO2 max) (r = -0.904, P < 0.05). The
      results illustrated that there was a stronger correlation between HR and VO2 max
      (r = 0.991, P < 0.001). The regression analysis of the quadratic equation also
      indicated that there was also a significant relationship between the VO2 max and
      HR. CONCLUSIONS: The results indicated that there was a strong relationship
      between the RPE and VO2 max, as well as a greater correlation between HR and VO2
      max. Therefore, the HR could be used as a Prediction measure to estimate VO2 max.

PMID- 25077149
TI  - Comparative study on the National Renal Disease Registry in America, England and
      Iran.
AB  - CONTEXT: A disease registry is a database that includes information about people
      diagnosed with specific types of diseases. The registry collects information that
      can be used for capturing, managing, and organizing specific information for
      patients. AIMS: The aim of this study was to identify and compare the National
      Renal Disease Registry (NRDR) in selected countries including the United States,
      United Kingdom, and Iran. SETTINGS AND DESIGN: Retrieval of data of the NRDR
      performed through scholars responsible in related agencies, including the
      Ministry of Health and Medical Education, and Renal Disease charity, and data
      registries in the United States, United Kingdom, and Iran. MATERIALS AND METHODS:
      This research was an applied and descriptive, comparative study. The study
      population consisted of the National Renal Disease Registry of the selected
      countries including the United States, United Kingdom, and Iran, from which data
      were collected using forms that were designed according to the study objectives.
      Sources of data were researchers, scholars responsible in related agencies,
      including the Ministry of Health and Medical Education, and Renal Disease
      charity, data registries, articles, books, journals, databases, websites, and
      related documents. Data were gathered through phone, e-mail, study, observation,
      and interview. STATISTICAL ANALYSIS USED: The researchers collected data for each
      country based on the study objectives and then put them in comparative tables.
      Data were analyzed by descriptive, comparative, and theoretical methods. RESULTS:
      There is no NRDR in Iran to report the short- and long-term results of renal
      disease. Most of the renal transplant teams report their own results as single
      center experiences. America and Britain have pre-eminent national registry of
      renal disease, compared to other countries. CONCLUSIONS: The Iranian Society of
      Nephrology should be actively involved to create a National Renal Registry in
      Iran. The registry should have representatives from the universities, government,
      armed forces, and private sectors. Researchers proposed to design the Iran
      National Renal Registry according to the UK Renal Disease Registry model because
      of its prominent healthcare system.

PMID- 25077150
TI  - Prediction of war veteran's mental health based on spiritual well-being, social
      support and self-efficacy variables: The mediating role of life satisfaction.
AB  - INTRODUCTION: The present study aims to provide a model for explaining the mental
      health of war veterans based on the variables of spiritual well-being, social
      support, and self-efficacy, with the mediating role of life satisfaction.
      MATERIALS AND METHODS: The research method was descriptive a correlational. The
      study samples included 210 veterans, who had records in the Veterans Foundation
      in Tehran's number one district, Sarallah and Imam Khomeini shelters and Essaar
      Sports Center in Tehran. They were selected randomly and were asked to respond to
      questionnaires on mental health, spiritual well-being, life satisfaction, social
      support, and self-efficacy. The data was analyzed by LISREL software version 8.5,
      using the path analysis. RESULTS: The results showed that the designed model
      fitted the data (AGFI = 1.00, RMSEA = 0.00 and NFI = 1.00). In the fitted model,
      life satisfaction and spiritual well-being directly, and social support
      indirectly, had a significant relationship with the mediator variable of life
      satisfaction of the war veterans' mental health. CONCLUSIONS: Veterans with
      better social support, life satisfaction, and spiritual well-being have better
      mental health.

PMID- 25077151
TI  - Perceived organizational support and job involvement in the Iranian health care
      system: A case study of emergency room nurses in general hospitals.
AB  - BACKGROUND AND OBJECTIVES: Researchers believe that there are social exchanges
      between the employers and employees, because the employees would be interested in
      their organization and trust it based on how the organization values them and
      their welfare, comfort, and security. This belief is known as perceived
      organizational support that makes employees consider themselves as a part of
      their organization and have a commitment to it. The literature review is very
      limited in both variables in Iran and thus few studies also report the perceived
      organizational support and job involvement at the lower levels in our country.
      This research aimed at studying the levels of perceived organizational support
      and job involvement, relationship between this two, and the demographic factors
      relationship with both of them. MATERIALS AND METHODS: This research was a
      descriptive analytical study conducted in 2012. The population included 123
      emergency nurses in General Hospitals of Qom. Data were collected through
      Perceived Organizational Support and Job Involvement Questionnaires and analyzed
      using SPSS software, descriptive statistics and Spearman correlation and Chi
      square test. RESULTS: Both mean scores for perceived organizational support and
      job involvement were in average level, 146/12 and 35/38, respectively. There was
      a significant relationship between perceived organizational support and age,
      education, tenure, organizational position, and job shift. There was also a
      significant relationship between job involvement and age and education and
      finally between perceived organizational support and job involvement (P = 0/029).
      DISCUSSION: The high correlation between perceived organizational support and job
      involvement indicates that the improvement of perceived organizational support
      are necessary through motivating the employees, showing interest in them, paying
      attention to them, respecting them, and providing development opportunity in the
      organization. These should be always considered by managers to improve job
      involvement.

PMID- 25077152
TI  - Health volunteers' knowledge of cardiovascular disease prevention and healthy
      lifestyle following a community trial: Isfahan healthy heart program.
AB  - BACKGROUND: Health volunteers can have a great effect by training the population
      about prevention of cardiovascular disease (CVD) and lifestyle modification. This
      study evaluated the health volunteers' knowledge following the Isfahan Healthy
      Heart Program (IHHP) that was performed between 2000 and 2006. MATERIALS AND
      METHODS: In this study, 491 females were selected among health volunteers in the
      Isfahan and Najafabad districts as intervention areas and Arak as a reference
      area through 2000-2001 until 2006. They participated in training courses on CVD,
      its complications, methods of prevention of risk factors control as well healthy
      lifestyle promotion. The health volunteers' level of knowledge was assessed
      before and after training. RESULTS: Before intervention, there was no significant
      difference between the scores of health volunteers in the intervention and the
      control regions in terms of knowledge about recognizing the symptoms,
      complications and prevention of CVD and relevant risk factors and healthy
      lifestyle. However, their knowledge scores increased significantly in the fields
      of CVD (beta = 0.13, P = 0.04), hypertension (beta = 0.18, P = 0.009), healthy
      nutrition (beta = 0.19, P = 0.007), appropriate physical activity (beta = 0.17, P
      = 0.01) and dealing with stress (beta = 0.16, P = 0.02) after trainings.
      CONCLUSION: The 6 year interventional program of IHHP showed that training health
      volunteers on prevention of CVD, their risk factors and modification of lifestyle
      continued to be effective even in a long time.

PMID- 25077154
TI  - The evaluation of hospital laboratory information management systems based on the
      standards of the American National Standard Institute.
AB  - INTRODUCTION: Nowadays, modern laboratories are faced with a huge volume of
      information. One of the goals of the Laboratory Information Management System
      (LIMS) is to assist in the management of the information generated in the
      laboratory. This study intends to evaluate the LIMS based on the standards of the
      American National Standard Institute (ANSI). MATERIALS AND METHODS: This research
      is a descriptive-analytical study, which had been conducted in 2011, on the LIMSs
      in use, in the teaching and private hospitals in Isfahan. The data collecting
      instrument was a checklist, which was made by evaluating three groups of
      information components namely: 'System capabilities', 'work list functions,' and
      'reporting' based on LIS8-A. Data were analyzed using the SPSS 20. Data were
      analyzed using (relative) frequency, percentage. To compare the data the
      following statistical tests were used: Leven test, t-test, and Analysis of
      Variance (ANOVA). RESULTS: The results of the study indicated that the LIMS had a
      low conformity (30%) with LIS8-A (P = 0.001), with no difference between teaching
      and private hospitals (P = 0.806). The ANOVA revealed that in terms of conformity
      with the LIS8-A standard, there was a significant difference between the systems
      produced by different vendors (P = 0.023). According to the results, a Kowsar
      system with more than %57 conformity in the three groups of information
      components had a better conformity to the standard, compared to the other
      systems. CONCLUSIONS: This study indicated that none of the LIMSs had a good
      conformity to the standard. It seems that system providers did not pay sufficient
      attention to many of the information components required by the standards when
      designing and developing their systems. It was suggested that standards from
      certified organizations and institutions be followed in the design and
      development process of health information systems.

PMID- 25077153
TI  - Temporomandibular joint health status in war veterans with post-traumatic stress
      disorder.
AB  - BACKGROUND AND AIM: The objective of this study was to determine the prevalence
      of signs and symptoms of temporomandibular joint dysfunction (TMJD) in the
      Iran/Iraq war veterans suffering from post-traumatic stress disorder. MATERIALS
      AND METHODS: A total of 120 subjects in the age range of 27 to 55 years were
      included; it included case group (30 war veterans with PTSD) and three control
      groups (30 patients with PTSD who had not participated in the War, 30 healthy war
      veterans, and 30 healthy subjects who had not participated in the War). All
      subjects underwent a clinical TMJ examination that involved the clinical
      assessment of the TMJ signs and symptoms. RESULTS: The groups of veterans had
      high prevalence of TMJD signs and symptoms vs. other groups; history of Trauma to
      joint was significantly higher in subjects who had participated in the war
      compare with subjects who had not participated in the war (P = 0.0006).
      Furthermore, pain in palpation of masseter, temporal, pterygoideus, digastric,
      and sternocleidomastoid muscles in the groups of veterans was significantly
      greater than other groups (P < 0.0001). Clicking noise during mouth chewing was
      significantly different between groups (P = 0.01). And, there was significant
      difference in the frequencies of maximum opening of the mouth between groups (P =
      0.001). CONCLUSION: The results of this study showed that subjects' war veterans
      with PTSD have significantly poorer TMJ functional status than the control
      subjects.

PMID- 25077155
TI  - Utility of the health belief model to assess predictors of rabies preventive
      measures.
AB  - INTRODUCTION: Rabies is a fatal zoonotic viral disease that is spread to people
      through animal bites. Around 35,000-50,000 individuals worldwide die of rabies
      each year, of which more than 99% of deaths occur in the developing countries.
      Since legislative actions does not appear to have been effective in reducing the
      incidence and severity of the bites in some developed countries, it seems public
      education is key to reducing animal bites. For effective education, understanding
      factors affecting the preventive and protective behaviors based on appropriate
      health behavior change models is important. So, the study tried to examine the
      relationship between Health Belief Model (HBM) constructs and rabies preventive
      measures. MATERIALS AND METHODS: In the cross-sectional study, a HBM-based
      researcher-designed questionnaire was completed by 204 participants who were
      selected via cluster sampling design from urban families of the Abadeh, Iran. The
      psychometric properties of the questionnaire were established. Descriptive
      statistics, independent sample t-test, bivariate correlations, and stepwise
      multiple regression analysis were applied to analyze data using SPSS 19. The
      level of significance was set a priori at 0.05. RESULTS: The scale mean for the
      total knowledge of the participants about rabies was 14.12 +/- 6.04 out of 29.
      Participants' preventive behaviors were significantly correlated with their total
      knowledge, perceived susceptibility, perceived severity, perceived benefits and
      cues to action, which 19% of the variation in these behaviors were explained by
      perceived benefits and cues to action. Protective activities of participants who
      kept animals in their house had statistically significant correlation with their
      total knowledge score and cues to action. 32.1% of the variation in these
      activities was explained by cues to action. DISCUSSION: Findings indicate that
      participants had not enough knowledge about routes of infecting by rabies and how
      to prevent it. The most powerful predictors for preventive behaviors and
      protective activities were perceived benefits and cues to action, respectively,
      which indicate the importance of the availability of accurate information about
      efficacy of these behaviors, from sources that are easily accessible, such as
      healthcare providers and veterinary professionals. CONCLUSION: Educational
      programs are needed for increasing public knowledge in this area. And more
      studies should be done to determine predictive factors of rabies preventive
      measures based on other health behavior change models.

PMID- 25077156
TI  - Evaluation of preventive effects of colostrum against neonatal conjunctivitis: A
      randomized clinical trial.
AB  - BACKGROUND: Neonatal conjunctivitis leads to several ocular consequences in the
      affected neonates such as blindness. Currently available therapeutic options
      include NaNO3, Gentamicin, Neomycin and so on, in which each of them has their
      own limitations. Regarding the immunologic content of colostrum and its safety
      and easy accessibility, we aimed to evaluate its preventive effects against
      neonatal conjunctivitis. MATERIALS AND METHODS: In this clinical trial, conducted
      from November 2011 to July 2012, 300 preterm neonates, with culture negative eye
      swab, were enrolled and randomly assigned into three groups. The intervention
      group received two drops of colostrum. Control group received no treatment and
      other neonates were treated with topical Erythromycin ointment (0.5%). All
      neonates were followed for occurrence of clinical conjunctivitis for 28 days.
      Data analysis were performed by Chi-square test. RESULTS: Our data demonstrate
      the beneficial preventive effects of Colostrum against neonatal conjunctivitis (P
      = 0.036). CONCLUSION: Colostrum is suggested as an alternative prophylactic
      option for antibiotics against neonatal conjunctivitis. As colostrum is easily
      accessible without cost, potential hazards and side effects, public education
      about its topical favorable effects is worthwhile.

PMID- 25077157
TI  - Factors affecting quality of life and fatigue in patients with leukemia under
      chemotherapy.
AB  - BACKGROUND: The goal of treating chronic diseases, including hematologic
      malignancies, is to increase patients' life span and to improve their
      capabilities as much as possible; so that patients could maintain an appropriate
      level of quality of life (QoL) and continue their lives. Most studies performed
      to evaluate the treatment of various diseases were mostly focused on the increase
      of life expectancy regardless of the QoL and treatment issues. Furthermore,
      fatigue is one of the most common and distressing side effects of cancer and
      treatments related to it, which can affect a patient's QoL, and be followed by
      many problems. This study was designed and implemented with the aim to determine
      the factors affecting the QoL and fatigue in patients with leukemia undergoing
      chemotherapy. MATERIALS AND METHODS: This was a cross-sectional correlation
      descriptive-analytical study. One hundred and fifteen patients with leukemia
      referred to Sayyed-Al-Shohada Hospital were enrolled in the study through
      convenient sampling method. To collect data, a three-part questionnaire was used:
      The first part was related to demographic characteristics and disease-related
      data and the second part was the fatigue check list and the third part was the
      Short-Form 36 Health Survey (SF-36) related to QoL. The data were analyzed after
      collection and coding through Software SPSS version 18 and descriptive and
      analytical statistics (analysis of variance test, independent t test, Pearson's
      and Spearman's correlation coefficient) with 95% confidence interval. RESULTS:
      The results showed that there was a significant correlation between QoL in
      Physical Component Summary with gender (P = 0.03), educational level (P = 0.09),
      and marital status (P = 0.004), Also there was a significant correlation between
      QoL in Mental Component Summary with educational level (P = 0.01) and economic
      status (P = 0.02). Findings showed that there was a significant correlation
      between fatigue and marital status (P = 0.005). But statistically there was no
      significant correlation between demographic variables such as age, educational
      level, and employment status with patients' fatigue. Spearman correlation
      coefficient showed that there was a significant correlation between fatigues with
      pain (P = 0.005). Also findings revealed the statistically significant
      correlation between fatigues with economic status (P = 0.003). CONCLUSION:
      According to the present results, it seems that some demographic factors affect
      QoL and significant relationship exists between them. Fatigue in patients with
      leukemia dramatically affects their QoL. Therefore, it is important for medical
      staff to pay attention to demographics and fatigue in leukemic patients in order
      to improve their QoL and help them to organize their activities to promote health
      and QoL.

PMID- 25077158
TI  - Understanding the factors affecting the postpartum depression in the mothers of
      Isfahan city.
AB  - BACKGROUND AND OBJECTIVE: Depression is one of the most common and specific
      problems during pregnancy and after it. Maternal postpartum depression
      compromises mother's health and affects social relationship, and has negative
      effect on infant development. The aim of this study was to investigate the
      prevalence of postpartum depression and its related factors in Isfahanian
      mothers. MATERIALS AND METHODS: This is a cross - sectional study. The study
      populations were 133 women who at the last 8-4 weeks of labor referred to Isfahan
      health centers. Demographic information and obstetric and Beck Depression
      Inventory were applied. Three categories emerged according to the degree of
      scale: Mild, moderate, and severe depression. Statistical analysis was used with
      the Pearson correlation and linear regression in SPSS version 18. RESULTS: A
      total of 73 mothers had mild depression (10-19) and 56 had moderate depressions
      (20-29). Among the factors related to depression such as maternal education,
      financial status, unwanted pregnancy, premenstrual syndrome, and maternal
      occupational history, there was a significant correlation with postpartum
      depression (P > 0.05). Variables in the regression analysis include maternal
      education, financial status, unwanted pregnancy, history of premenstrual
      syndrome, maternal occupation, type of delivery, history of miscarriage, and
      having a satisfaction with baby gender. And, a total of 27.7% variance explains
      the postpartum depression. Among these factors, the predictive variables of
      maternal education, type of delivery, financial condition, unwanted pregnancy,
      premenstrual syndrome, and maternal occupational history were significant in the
      meantime; the prediction of unplanned pregnancy was more than other variables
      (beta = 0.24). CONCLUSIONS: With attention to factors associated with postpartum
      depression, the healthcare planner will help to better manage the problem. The
      results of this study will help to better understand the factors influencing
      mothers in the labor process, and mothers in the labor process, experiences
      minimum mental health disorders.

PMID- 25077159
TI  - A survey on health literacy of inpatient's educational hospitals of Isfahan
      University of Medical Sciences in 2012.
AB  - BACKGROUND: Health literacy is an individual's need in each Society. Health
      literacy is a set of skills in reading, listening, analysis, decision making and
      the ability to apply these skills to health situations. The purpose of this study
      was to assess health literacy level in Inpatients of educational Hospitals of
      Isfahan University of Medical Sciences in 2012. MATERIALS AND METHODS: A
      navigational and analytical- applied survey of 384 Inpatients was conducted in
      educational hospitals of Isfahan University of Medical Sciences. Health literacy
      was measured by the Test of Functional Health Literacy in Adults (TOFHLA).
      Reliability of Questionnaire was obtained through Cronbach's alpha and it was
      0/89 and its validity was confirmed by experts. The data were collected in
      clinical inquiry and were analyzed using SPSS (as Descriptive was Frequency
      distribution, mean, standard deviation and as analytical was Independent T-test,
      ANOVA and Pearson correlation test and Spearman correlation test). FINDINGS:
      Results showed that the average of Health literacy scores in Inpatients was 35/31
      in Numeracy test and 31/94 in Reading Comprehension test. The mean total score of
      health literacy was 29/63. Thus, the Most of these Inpatients were found to have
      inadequate health literacy. No significant association was found between health
      literacy level and gender, income, Occupation and residence. Health literacy was
      associated with age, marriage status and education. CONCLUSION: The results
      showed that most of Inpatients in of educational Hospitals of Isfahan University
      of Medical Sciences were marginal and inadequate health literacy. Therefore, they
      need to more help and details to understand and use health information.

PMID- 25077160
TI  - A comparative study of the attitudes of managers, employees and clients in the
      field of social barriers of family planning counseling in health care centers of
      Isfahan in 2012.
AB  - BACKGROUND: Appropriate family planning counseling for informed choice, the right
      and responsible use of contraceptive methods is very important. Various barriers
      such as social barriers can have the effect on family planning counseling. In
      addition, investigation of those barriers from the perspective of managers, staff
      and clients, who are major members in health care system, has great importance.
      The present study was conducted with the goal of comparing managers', employees',
      and clients' viewpoints about social barriers in family planning counseling in
      health care centers in Isfahan in 2012. MATERIALS AND METHODS: This is a cross
      sectional one-step three-group comparative descriptive study conducted on 295
      subjects including 59 managers, 110 employees, and 126 clients in medical health
      care centers in Isfahan in 2012. Managers and employees were selected by census
      sampling and the clients were recruited through convenient random sampling. The
      data collection tool was a researcher made questionnaire, which was designed in
      two sections of fertility and personal characteristics and viewpoint measurement.
      Descriptive and inferential statistical test were used to analyze the data.
      RESULTS: The obtained results showed significant difference between mean scores
      of viewpoints in three groups of managers, employees, and clients concerning
      social barriers in family planning counseling (P = 0.001). In addition, most of
      the managers and employees reported social barriers as the barriers in process of
      family planning in a large level and clients reported it in moderate level.
      CONCLUSION: The results express the necessity of health services managers'
      planning to modify or delete social barriers, especially the agreed barriers from
      the viewpoint of managers and employees that effect on family planning counseling
      and quality of service provided by them.

PMID- 25077161
TI  - The relationship of Alexithymia with anxiety-depression-stress, quality of life,
      and social support in Coronary Heart Disease (A psychological model).
AB  - BACKGROUND: Although psychological factors are now recognized as playing a
      significant and independent role in the development of coronary heart disease
      (CHD) and its complications, many of these factors are correlated with each
      other. The present study is aimed at examining the association between
      alexithymia and anxiety depression, stress, quality of life, and social support
      in CHD patients. MATERIALS AND METHODS: In this research 398 patients with
      coronary heart disease (166 females and 232 males) from the city of Isfahan were
      selected using random sampling. The tools used included depression, anxiety, and
      stress scale (DASS-21), Health-related to Quality Of Life (HRQOL-26), Multiple
      Scale Perceived Social Support (MSPSS-12), and the Toronto Alexithymia Scale (TAS
      20). The data were analyzed using structural equation modeling by using the
      Statistical Package for Social Science (SPSS21) (IBM Corp: Armonk, New York.U.S.)
      and Asset Management Operating System (AMOS21) SPSS, an IBM Company: Chicago,
      U.S. Software. RESULTS: Results of the structural equation model showed an
      acceptable goodness of fit, for the explanation alexithymia that was
      significantly associated with lower HRQOL and social support and increasing
      anxiety, depression, and stress. CONCLUSIONS: Alexithymia may increase anxiety,
      depression, and stress and can be a predisposing factor to poorer HRQOL and
      social support.

PMID- 25077162
TI  - Hormonal and reproductive risk factors associated with breast cancer in Isfahan
      patients.
AB  - BACKGROUND: Breast cancer is the most prevalent type of cancer among Iranian
      females; it is noteworthy that the condition of this type of cancer among Iranian
      women does not significantly differ from what has been reported from other
      countries. Considering the importance of this issue, identification of the
      backgrounds factors and risk factors of the breast cancer risk are highly needed.
      Therefore, the present study is aimed to compare the risk factors of resident
      patients of Isfahan province, Iran, with accredited risk factors by other
      countries and also identify the importance of each factor in the incidence of
      cancer. MATERIALS AND METHODS: The present work is a case-control study, which
      was conducted in 2011. In order to conduct the study, 216 women who had been
      clinically identified with breast cancer were selected from Seiedo-Shohada
      Hospital, Isfahan, Iran, as the case group. Moreover, 41 healthy women who were
      the relatives of the selected patients (i.e., sisters and aunts) were selected as
      the control group. The data and information of the patients from 1999 to 2010
      were collected from either assessing the database system of the center for breast
      cancer research or interviewing the patients through phone. To analyze the data,
      multiple logistic regression method was applied. RESULTS: The range of age among
      selected individuals in this study was from 20-75 years old. The determinant
      factors for odds of breast cancer included in the applied multiple logistic
      regression model were the use of oral contraceptive pills (OCPs) (odds ratio [OR]
      =0.18, 95% confidence interval [CI] = 0.04-0.75) as the protective factor,
      hormone replacement therapy (OR = 10.2, 95% CI = 1.18-88.89) and menopause at old
      age (OR = 1.26, 95% CI = 1.11-2.12) as the risk factors. Furthermore, there was
      not seen any significant relationship between age, vocation, and marital status
      with odds of breast cancer in multiple model. CONCLUSION: Based on the results,
      use of OCPs as protective factor, hormone replacement therapy, and menopause at
      old age are identified as the risk factors in developing breast cancer among
      women. Influencing and modifiable factors should be considered very important in
      society based interventions and preventive interventions planning.

PMID- 25077163
TI  - The effect of stress management training on stress and depression in women with
      depression disorders: Using cognitive-behavioral techniques.
AB  - BACKGROUND: The present study aimed to investigate the effect of stress
      management training through cognitive-behavioral techniques on stress, social
      adaptability and depression in women with depression disorders. MATERIALS AND
      METHODS: In this study, 40 patients diagnosed with depression who had referred to
      psychiatry and consultation clinics of Isfahan were randomly selected and
      assigned to intervention and control groups (20 patients in each group). The
      intervention group received eight 90-min sessions of stress training through
      cognitive-behavioral techniques. Data collection tools included Cooper's stress
      questionnaire, Bell's social adaptability questionnaire and Hamilton's depression
      scale questionnaire. The participants completed the questionnaires before the
      intervention and 1 month after the same. Data analysis was performed using
      covariance analysis. RESULTS: Based on the results, considering variables of
      stress, social adaptability and depression, the equal variance hypothesis was
      confirmed. The relationship between pre- and post-test scores on stress, social
      adaptability and depression was statistically significant (P < 0.001). The
      modified mean difference was F = 12.45, P < 0.001 on stress; F = 6.88, P < 0.01
      on social adaptability; and F = 5.36, P < 0.02 on depression, all of which were
      significant. CONCLUSION: Stress management training through cognitive behavioral
      techniques can play a main role in depression reduction and development of social
      adaptability through modifying inappropriate social information-processing
      patterns.

PMID- 25077164
TI  - The psychometric properties of cellular phone dependency questionnaire in
      students of Isfahan: A pilot study.
AB  - BACKGROUND: A number of diagnostic scales or questionnaires have been developed
      in recent years, to assess mobile phone dependency. A valid and reliable
      assessment instrument for correspondence of Iranian culture is essential. The aim
      of our study is to validate the Iranian version of the Cell Phone Dependency
      Questionnaire (CPDQ). MATERIALS AND METHODS: In this cross-sectional study, data
      were collected from 784 students, who were studying in four main Isfahan
      Universities. The participants completed the demographic questionnaire, CPDQ,
      anonymously. To analyze the data we used concurrent validity, factor analysis,
      internal consistency, split-half, and test-retest. RESULTS: We extracted three
      factors including Salience, Overusing of the cell phone, compulsive use of SMS.
      Cronbach's alpha of the CPDQ was. 88 (Cronbach's alpha of the factors were 0.85,
      0.70, and 0.76, respectively). CONCLUSION: The CPDQ proved to be a reliable
      questionnaire to assess the extent of problems caused by the 'misuse' of the cell
      phone in Iranian society.

PMID- 25077165
TI  - The effects of state anxiety and thermal comfort on sleep quality and eye fatigue
      in shift work nurses.
AB  - Psychological problems as state anxiety (SA) in the work environment has negative
      effect on the employees life especially shift work nurses, i.e. negative effect
      on mental and physical health (sleep quality, eye fatigue and comfort thermal).
      The purpose of this study was determination of effects of state anxiety and
      thermal comfort on sleep quality and eye fatigue in shift work nurses. METHODS:
      This cross-sectional research conducted on 82 shift-work personnel of 18 nursing
      workstations of Isfahan hospitals in 2012. To measure the SA, sleep quality,
      visual fatigue and thermal comfort, Spielberger state-trait anxiety inventory,
      Pittsburg sleep quality index, eye fatigue questionnaire and thermal comfort
      questionnaire were used respectively. The data were analyzed with descriptive
      statistics, student test and correlation analysis. RESULTS: Correlation between
      SA and sleep quality was -0.664(P < 0001), Pearson correlation between SA and
      thermal comfort was -0.276(P = 0.016) and between SA and eye fatigue was 0.57 (P
      < 0001). CONCLUSION: Based on these results, it can be concluded that improvement
      of thermal conditions and reduce state anxiety level can be reduce eye fatigue
      and increase the sleep quality in shift work nurses.

PMID- 25077166
TI  - Student perception about efficacy of preclinical fixed prosthodontic training to
      facilitate smooth transition to clinical context.
AB  - BACKGROUND: Studies indicate that the initial transition period between
      preclinical and clinical phases are the most stressful. The students have
      experienced the difficulty in performing clinical procedures due to the vast
      difference in the clinical and preclinical setup. It is better to identify the
      particular skill found poorly correlated, enabling educators to address the
      concerns. We sought the opinion and suggestion from the beneficiary student on
      fixed prosthodontics steps difficult to practice in clinical setup at the initial
      stage, their suggestion to overcome these shortcomings was also sought. AIMS: To
      determine the fixed prosthodontics skills difficult to perform in a transition
      period due to poor correlation between preclinical and clinical training from our
      focus group study on the student's perception, and their suggestion regarding
      alternative methods to improve the preclinical training. MATERIALS AND METHODS:
      Focus groups in the study were the students involved in clinical practice of
      fixed partial denture procedure. A well-constructed Questionnaire, designed to
      evaluate the difficult clinical steps in a transitional period and suggestion to
      improve the existing preclinical training was distributed to all focus group
      students. The response to the questionnaire was based on the five-point Likert
      scale. STATISTICAL ANALYSIS USED: Medians, frequencies were used to assess their
      perception on preclinical training and suggestion. RESULTS: A total of 97
      students participated in the study, 88% response received during the survey. The
      clinical steps student felt difficult during a transition period from preclinical
      to clinical phase were positional variations of teeth (52.6%-63.9%), fluid
      control (48.5-67.1%), shade selection procedure (29.9%-50.5%), subgingival
      cervical finish line preparation (38.1-51.5%), and gingival retraction procedure.
      The students felt that the inclusion of problem-based learning, preclinical
      patient exposure, and better simulation will alleviate the stress during the
      transition period. CONCLUSIONS: This study highlighted the tooth preparation
      steps found difficult to practice in a transition period between preclinical and
      clinical phases. This study also obtained suggestions from the students for
      innovative upgradation of the course curricula.

PMID- 25077167
TI  - Are obese adolescents more depressed?
AB  - INTRODUCTION: Obesity is a growing problem in all countries which leads to
      various physical, psychological, and social problems. The present study aimed to
      assess depression in children and adolescents aged 10-18-year old compared with
      the control group. MATERIALS AND METHODS: In a case-control study, from among the
      10- to 18-year-old students of the five education districts of Isfahan, 100
      people (50 girls and 50 boys) were selected as obese children with the Body Mass
      Index (BMI) of greater than 95(th) percentile for their age and gender and 100
      others (50 girls and 50 boys) as the control group with the BMI of 5(th) to
      85(th) percentile. The case and control groups were matched for age, gender, and
      socio-economic status. After calculating BMI based on weight (kg)/height(2)
      (meter), subjects were interviewed based on DSM IV criteria to diagnose clinical
      depression. The severity of children's depression was measured using standardized
      questionnaire. RESULTS: The mean age of the case group was 12.2 +/- 1.86-years
      old and that of the control group 13.06 +/- 2.25. They were, respectively,
      diagnosed with depression of 7% and 6%. The mean depression score of the case
      group was 11.7 +/- 5.3 and that of the control group was 10.6 +/- 6.03 with no
      statistical significance. DISCUSSION: Given our findings, the Jolly fat
      hypothesis applies to the case group. It seems that health policy-makers need to
      make intervention plans to change behavior; attitude, skill, and knowledge (BASK)
      of the public toward obesity and its long-term side-effects.

PMID- 25077168
TI  - The relationship between health literacy with health status and healthcare
      utilization in 18-64 years old people in Isfahan.
AB  - BACKGROUND: Today, much attention has been paid to the patient role as the
      central factor in the management of their own health. It is focused on the issue
      that the patient has a more critical role compared with the health-care provider
      in controlling the patient own health. defines health literacy 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.
      OBJECTIVE: The objective of this study was to determine health literacy, health
      status, healthcare utilization and the relationship between them in 18 - 64 years
      old people in Isfahan. STRUCTURE AND DESIGN: This study was a descriptive
      analytical survey, which was conducted on 300 subjects of 18-64 years old in
      Isfahan with Multi-stage sampling method proportional to selected sample size.
      MATERIALS AND METHODS: For collecting the data, questionnaire adapted from CHAP
      (Consumer Assessment of Healthcare Providers and Systems) health literacy
      questionnaire was used. Health status was measured based on an assessment of the
      physical and mental health over the past 6 months by 5 degrees  Likert scale.
      Data analysis was performed by using SPSS 18, descriptive statistics, Chi-square
      test and multivariate analysis of variance. RESULTS: There was no significant
      correlation between health literacy, health status and healthcare utilization.
      Utilization was less in the urban area No. 6 of the city. In the bachelor's
      degree group, the health status was lower than the other groups in these cases:
      Older ages, married, women, large family size, undergraduates, and urban area No.
      14. CONCLUSIONS: Due to the average prevalence of health literacy in 18-64 years
      old individuals in Isfahan and low- healthcare utilization, the followings are
      recommended: Necessity of more attention to the issue of health literacy,
      improving the physician-patient relationship and community awareness, whether
      through health promotion programs or media for the optimum use of available
      resources.

PMID- 25077169
TI  - Re-defininG AddiC(CH3)Tion: genomics and epigenomics on substance use disorders.

PMID- 25077170
TI  - Genetics and genomics in Brazil: a promising future.

PMID- 25077171
TI  - 46,XY disorder of sexual development resulting from a novel monoallelic mutation
      (p.Ser31Phe) in the steroid 5alpha-reductase type-2 (SRD5A2) gene.
AB  - Inactivating mutations of the 5alpha-steroid reductase type-2 (SRD5A2) gene
      result in a broad spectrum of masculinization defects, ranging from a male
      phenotype with hypospadias to a female phenotype with Wolffian structures.
      Molecular studies of the SRD5A2 revealed a new heterozygous gene variant within
      the coding region that results in phenotypic expression. A c.92C>T transition
      changing serine to phenylalanine at codon 31 of exon 1 (p.Ser31Phe) was
      identified in a patient with 46,XY disorder of sexual development who displayed
      glandular hypospadias with micropenis and bilateral cryptorchidism. The
      restoration of the p.Ser31Phe mutation by site-directed mutagenesis and transient
      expression assays using cultured HEK-293 cells showed that this novel
      substitution does not abolish but does deregulate the catalytic efficiency of the
      enzyme. Thus, the maximum velocity (V max) value was higher for the mutant enzyme
      (22.5 +/- 6.9 nmol DHT mg protein(-1) h(-1)) than for the wild-type enzyme (9.8
      +/- 2.0 nmol DHT mg protein(-1) h(-1)). Increased in vitro activity of the
      p.Ser31Phe mutant suggested an activating effect. This case provides evidence
      that heterozygous missense mutations in SRD5A2 may induce the abnormal
      development of male external genitalia. 

PMID- 25077172
TI  - Mutation spectrum and genotype-phenotype correlations in a large French cohort of
      MYH9-Related Disorders.
AB  - MYH9-Related Disorders are a group of rare autosomal dominant platelet disorders
      presenting as nonsyndromic forms characterized by macrothrombocytopenia with
      giant platelets and leukocyte inclusion bodies or as syndromic forms combining
      these hematological features with deafness and/or nephropathy and/or cataracts.
      They are caused by mutations in the MYH9 gene encoding the nonmuscle myosin heavy
      chain II-A (NMMHC-IIA). Until now, at least 49 MYH9 mutations have been reported
      in isolated cases or small series but only rarely in large series. We report the
      results of an 8-year study of a large cohort of 109 patients from 37 sporadic
      cases and 39 unrelated families. We have identified 43 genetic variants, 21 of
      which are novel to our patients. A majority, 33 (76.7%), were missense mutations
      and six exons were preferentially targeted, as previously published. The other
      alterations were three deletions of one nucleotide, one larger deletion of 21
      nucleotides, and one duplication. For the first time, a substitution T>A was
      found in the donor splice site of intron 40 (c.5765+2T>A). Seven patients, four
      from the same family, had two genetic variants. The analysis of the genotype
      phenotype relationships enabled us to improve the knowledge of this heterogeneous
      but important rare disease. 

PMID- 25077173
TI  - Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide
      hydrolase gene with anorexia nervosa in the Japanese population.
AB  - The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid
      amide hydrolase (FAAH) gene, one of the major degrading enzymes of
      endocannabinoids, is reportedly associated with anorexia nervosa (AN). We
      genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control
      participants in Japan. There were significant differences in the genotype and
      allele frequencies of c.385C>A between the AN and control groups. The minor 385A
      allele was less frequent in the AN participants than in the controls (allele
      wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653-0.976, P = 0.028).
      When the cases were subdivided into lifetime restricting subtype AN and AN with a
      history of binge eating or purging, only the restricting AN group exhibited a
      significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557-0.922, P =
      0.0094). Our results suggest that having the minor 385A allele of the FAAH gene
      may be protective against AN, especially restricting AN. This finding supports
      the possible role of the endocannabinoid system in susceptibility to AN. 

PMID- 25077174
TI  - Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype
      suggesting a link between autosomal recessive cutis laxa type 3A and Warburg
      Micro syndrome.
AB  - Autosomal recessive cutis laxa type 3A is caused by mutations in ALDH18A1, a gene
      encoding the mitochondrial enzyme Delta(1)-pyrroline-5-carboxylate synthase
      (P5CS). It is a rare disorder with only six pathogenic mutations and 10 affected
      individuals from five families previously described in the literature. Here we
      report the identification of novel compound heterozygous missense mutations in
      two affected siblings from a Lebanese family by whole-exome sequencing. The
      mutations alter a conserved C-terminal domain of the encoded protein and reduce
      protein stability as determined through Western blot analysis of patient
      fibroblasts. Patient fibroblasts exhibit a lipid droplet phenotype similar to
      that recently reported in Warburg Micro syndrome, a disorder with similar
      features but hitherto unrelated cellular etiology. 

PMID- 25077175
TI  - Telomere length, family history, and paternal age in schizophrenia.
AB  - Leukocyte telomere length (LTL) is longer in association with advanced paternal
      age, but this association has not been examined along with family history (FH) in
      schizophrenia. LTL was measured by PCR and compared across cases and controls as
      part of a study to examine the characteristics of paternal age related
      schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls,
      although cases were significantly older than controls and overwhelmingly smoked
      cigarettes. Multivariate analyses showed that a FH of schizophrenia was
      associated with longer LTL in both male and female cases. Later paternal age was
      also related to longer LTL in male cases, but with shorter LTL in female cases.
      Male cases with older fathers and a FH had the longest LTL. The genetic
      architecture associated with a familial risk for schizophrenia may include
      pathways that lengthen LTL. Paternal aging conferred an additional increase in
      LTL lengthening in male cases, but reduced LTL in female cases. The gender
      difference in LTL for paternal aging is consistent with the severe illness
      features reported for female cases with older fathers and could implicate
      epigenetic alterations in the paternal X chromosomal region with advanced
      paternal age in association with the risk for schizophrenia. 

PMID- 25077176
TI  - A-TWinnipeg: Pathogenesis of rare ATM missense mutation c.6200C>A with decreased
      protein expression and downstream signaling, early-onset dystonia, cancer, and
      life-threatening radiotoxicity.
AB  - We studied 10 Mennonite patients who carry the c.6200C>A missense mutation
      (p.A2067D) in the ATM gene, all of whom exhibited a phenotypic variant of ataxia
      telangiectasia (A-T) that is characterized by early-onset dystonia and late-onset
      mild ataxia, as previously described. This report provides the pathogenetic
      evidence for this mutation on cellular functions. Several patients have developed
      cancer and subsequently experienced life-threatening adverse reactions to
      radiation (radiotoxicity) and/or chemotherapy. As the c.6200C>A mutation is, thus
      far, unique to the Mennonite population and is always associated with the same
      haplotype or haplovariant, it was important to rule out any possible confounding
      DNA variant on the same haplotype. Lymphoblastoid cells derived from Mennonite
      patients expressed small amounts of ATM protein, which had no autophosphorylation
      activity at ATM Ser1981, and trace-to-absent transphosphorylation of downstream
      ATM targets. A-T lymphoblastoid cells stably transfected with ATM cDNA which had
      been mutated for c.6200C>A did not show a detectable amount of ATM protein. The
      same stable cell line with mutated ATM cDNA also showed a trace-to-absent
      transphosphorylation of downstream ATM targets SMC1pSer966 and KAP1pSer824. From
      these results, we conclude that c.6200A is the disease-causing ATM mutation on
      this haplotype. The presence of at least trace amounts of ATM kinase activity on
      some immunoblots may account for the late-onset, mild ataxia of these patients.
      The cause of the dystonia remains unclear. Because this dystonia-ataxia phenotype
      is often encountered in the Mennonite population in association with cancer and
      adverse reactions to chemotherapy, an early diagnosis is important. 

PMID- 25077177
TI  - Haploinsufficiency of insulin gene enhancer protein 1 (ISL1) is associated with d
      transposition of the great arteries.
AB  - Congenital heart defects are the most common malformation, and are the foremost
      causes of mortality in the first year of life. Among congenital heart defects,
      conotruncal defects represent about 20% and are severe malformations with
      significant morbidity. Insulin gene enhancer protein 1 (ISL1) has been considered
      a candidate gene for conotruncal heart defects based on its embryonic expression
      pattern and heart defects induced in Isl1 knockout mice. Nevertheless no mutation
      of ISL1 has been reported from any human subject with a heart defect. From a
      population base of 974,579 births during 1999-2004, we used multiplex ligation
      dependent probe amplification to screen for microdeletions/duplications of ISL1
      among 389 infants with tetralogy of Fallot or d-transposition of the great
      arteries (d-TGA). We also sequenced all exons of ISL1. We identified a novel 20
      kb microdeletion encompassing the entire coding region of ISL1, but not including
      either flanking gene, from an infant with d-TGA. We confirmed that the deletion
      was caused by nonhomologous end joining mechanism. Sequencing of exons of ISL1
      did not reveal any subject with a novel nonsynonymous mutation. This is the first
      report of an ISL1 mutation of a child with a congenital heart defect. 

PMID- 25077178
TI  - Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair
      protein.
AB  - In clinical genetic diagnostics, it is difficult to predict whether genetic
      mutations that do not greatly alter the primary sequence of the encoded protein
      causing unknown functional effects on cognate proteins lead to development of
      disease. Here, we report the clinical identification of c.2038 T>C missense
      mutation in exon 18 of the human MLH1 gene and biochemically characterization of
      the p.Cys680Arg mutant MLH1 protein to implicate it in the pathogenicity of the
      Lynch syndrome (LS). We show that the mutation is deficient in DNA mismatch
      repair and, therefore, contributing to LS in the carriers. 

PMID- 25077179
TI  - Kawasaki disease patients homozygous for the rs12252-C variant of interferon
      induced transmembrane protein-3 are significantly more likely to develop coronary
      artery lesions.

PMID- 25077285
TI  - [Nosocomial diarrhea in young children: pacifiers are not a risk].

PMID- 25077181
TI  - Agroinfiltration as an Effective and Scalable Strategy of Gene Delivery for
      Production of Pharmaceutical Proteins.
AB  - Current human biologics are most commonly produced by mammalian cell culture
      based fermentation technologies. However, its limited scalability and high cost
      prevent this platform from meeting the ever increasing global demand. Plants
      offer a novel alternative system for the production of pharmaceutical proteins
      that is more scalable, cost-effective, and safer than current expression
      paradigms. The recent development of deconstructed virus-based vectors has
      allowed rapid and high-level transient expression of recombinant proteins, and in
      turn, provided a preferred plant based production platform. One of the remaining
      challenges for the commercial application of this platform was the lack of a
      scalable technology to deliver the transgene into plant cells. Therefore, this
      review focuses on the development of an effective and scalable technology for
      gene delivery in plants. Direct and indirect gene delivery strategies for plant
      cells are first presented, and the two major gene delivery technologies based on
      agroinfiltration are subsequently discussed. Furthermore, the advantages of
      syringe and vacuum infiltration as gene delivery methodologies are extensively
      discussed, in context of their applications and scalability for commercial
      production of human pharmaceutical proteins in plants. The important steps and
      critical parameters for the successful implementation of these strategies are
      also detailed in the review. Overall, agroinfiltration based on syringe and
      vacuum infiltration provides an efficient, robust and scalable gene-delivery
      technology for the transient expression of recombinant proteins in plants. The
      development of this technology will greatly facilitate the realization of plant
      transient expression systems as a premier platform for commercial production of
      pharmaceutical proteins.

PMID- 25077286
TI  - The clinical aspects of oxygen and methods related to its measurement.

PMID- 25077287
TI  - Use of the continuous glucose monitoring system to treat  insulin autoimmune
      syndrome: quantification of glucose  excursions and evaluation of treatment
      efficacy.
AB  - BACKGROUND: Autoimmune hypoglycaemia, based on the presence of autoantibodies
      directed against endogenous insulin (insulin autoimmune syndrome or Hirata's
      disease), is a rare cause of hypoglycaemia. Treatment of the disease is not
      standardized and various therapeutic options have been proposed. We wondered
      whether using a continuous glucose-monitoring system could help quantify
      precisely glucose excursions and allow evaluation of treatment efficacy. CASE
      REPORT: A 44-year-old Caucasian patient with insulin autoimmune syndrome was
      studied for 7 days using a continuous glucose monitoring system under various
      treatment regimens, i.e. diet modification, high-dose corticosteroids, alpha
      glucosidase inhibitors, and plasmapheresis. CONCLUSION: Continuous glucose
      monitoring system data confirmed that insulin autoimmune syndrome alternated
      between periods of prandial hyperglycaemia and interprandial hypoglycaemia. Alpha
      glucosidase inhibitors and plasmapheresis were more potent in limiting glucose
      excursions than corticosteroid or diet-only treatments. The continuous glucose
      monitoring system appears to be a useful tool in the management of insulin
      autoimmune syndrome.

PMID- 25077288
TI  - Exploring interference from analgesia in patients with cancer pain: a
      longitudinal qualitative study.
AB  - AIMS AND OBJECTIVES: To increase understanding of the impact of analgesic side
      effects in patients with cancer pain. BACKGROUND: Studies in the area of cancer
      pain often refer to the need to find a satisfactory balance between analgesics
      and side effects as the key to cancer pain management. We explore how patients
      achieve this balance, its components and how it affects pain treatment adherence.
      DESIGN: An exploratory longitudinal study using qualitative research methodology.
      METHODS: Twenty-five semi-structured face-to-face interviews with patients with
      advanced cancer and their caregivers. Longitudinal interviews were conducted with
      patients (n = 11) at six-week intervals over three months. Eleven first
      interviews, eight second interviews and six third interviews were completed with
      attrition due to death or ill health. Ten of the 25 interviews included
      caregivers. RESULTS: How cancer pain analgesics interfere with patients' life
      determines their adherence to the prescribed treatment. Compromises were made to
      manage three elements: pain, cognitive adverse effects of analgesics and physical
      activity. Negotiations and choices within this triad fluctuated and were
      determined by multiple psychosocial circumstances affecting patients and their
      caregivers varying from simple to complex. Patients with cancer and their
      caregivers actively managed the interference of analgesic drugs in their
      cognitive abilities and displayed a variety of nonadherence behaviours.
      CONCLUSION: Further understanding of the role of analgesic side effects in the
      success of cancer pain management in patients is needed. This would enable
      clinicians to frame an optimal pain management plan. RELEVANCE TO CLINICAL
      PRACTICE: Clinicians should advise their patients about side effects of analgesic
      drugs, specifically the impact that cognitive alterations might have on their
      lives and subsequent adherence behaviour. Helping patients to achieve a balance
      between pain, adverse effects and physical function should have a key place in
      pain management strategies with advanced cancer.

PMID- 25077289
TI  - Timing and mechanism of the initial cue establishing handed left-right asymmetry
      in Caenorhabditis elegans embryos.
AB  - By the six-cell stage, embryos of Caenorhabditis elegans are morphologically L-R
      asymmetric with an invariant handedness that persists throughout development. We
      used intracellular markers to ask whether breaking of L-R symmetry could be
      observed at earlier stages. Observation of two- to three-cell embryos carrying
      intracellular markers indicated that L-R symmetry is broken concomitantly with
      establishment of D-V axis polarity during division of the anterior AB cell. The
      AB cleavage furrow initiates asymmetrically and always from the left, suggesting
      L-R differences in the AB cell cortex. An invariantly handed cortical rotation
      observed earlier during first cleavage implies that the one-cell embryo has an
      intrinsic chirality. We propose that L-R differences in the cortex could result
      from mechanical forces on asymmetric components of a chiral cortical network
      during the off-axis elongation of the AB-cell spindle prior to AB cleavage.

PMID- 25077291
TI  - Reply to Ahad et al.: Source apportionment of polycyclic aromatic hydrocarbons in
      the Athabasca oil sands region is still a work in progress.

PMID- 25077290
TI  - Validity of criteria for hospital admission in exacerbations of COPD.
AB  - AIMS: To validate a previously developed set of explicit criteria for the
      appropriateness of hospital admission among these patients using the RAND/UCLA
      Appropriateness Methodology (RAM). METHODS: We conducted a prospective cohort
      study of patients experiencing symptoms of COPD exacerbation seen in the
      emergency departments (ED) of 16 hospitals belonging to the Spanish National
      Health Service. Sociodemographic and clinical variables needed to assess
      appropriateness were recorded. Main outcomes were mortality, severe COPD
      evolution, complications at follow up, and three patient-reported measures:
      dyspnoea level, capacity for physical activity and perceived health status.
      RESULTS: Appropriately admitted patients were more likely to die (6.70% vs.
      2.68%, p = 0.0102) than inappropriately admitted patients, and were more likely
      to develop severe evolution (27.09% vs. 6.08%, p < 0.0001) and complications
      (18.72% vs. 11.92%, p = 0.0244). Among discharged patients, no significant
      differences were observed in clinical outcomes. All patients exhibited worse
      dyspnoea and capacity for physical activity after exacerbation, but changes among
      appropriately admitted patients were less than among appropriately discharged
      patients. CONCLUSION: Our appropriateness criteria identified patients in worse
      condition at ED arrival who were more likely to benefit from admission in terms
      of mortality and COPD evolution.

PMID- 25077292
TI  - Reply to Drury and Theall: No evidence of population stratification.

PMID- 25077293
TI  - Raising the bar in private duty in-home   clinical quality standards.

PMID- 25077294
TI  - Get acquainted with "Physician   Compare".

PMID- 25077295
TI  - Proceedings of the International Wildlife Tuberculosis Conference, September 9
      12, 2012, Skukuza, South Africa.

PMID- 25077297
TI  - Abstracts of the British Association of Urological Surgeons Annual Meeting, 23-26
      June 2014, Liverpool, UK.

PMID- 25077296
TI  - Proceedings of the international workshop entitled "Human Disorders of Copper
      Metabolism: Recent Advances and Main Challenges", April 8-9, 2013, Baltimore,
      Maryland.

PMID- 25077298
TI  - Proceedings of the Ninth International Workshop on Neonatology, October 2013,
      Cagliari, Italy.

PMID- 25077299
TI  - [Not Available].

PMID- 25077300
TI  - [Not Available].

PMID- 25077301
TI  - HMG-CoA reductase inhibitors (statins), inflammation, and endothelial progenitor
      cells-New mechanistic insights of atherosclerosis.
AB  - Statins have been shown to favorably affect the prognosis of patients with risk
      factors to atherosclerosis-both as a primary and a secondary prevention. The
      beneficial effects observed with statin therapy are not merely related to changes
      in lipid profile but also are due to a positive effect on vascular inflammation
      and on immune-modulation of T lymphocytes and endothelial progenitor stem cells
      (EPCs). This dual effect has been demonstrated mainly in clinical trials where a
      change in endothelial function was observed within hours, much earlier than the
      effects of statins on the lipid profile (weeks). Based on all the knowledge that
      we have today questions were raised as to the mechanistic pathways that may
      explain the process of atherosclerosis and through this pathway to find better
      solutions and therapies to prevent and fight atherosclerosis. Our review will
      focus on the new updates in the field of inflammation and stem cells in vascular
      biology-in relation with atherosclerosis.

PMID- 25077302
TI  - [The 2012 Bucharest Declaration of the International Federation of Kidney
      Foundation].

PMID- 25077303
TI  - Results of acoustic neuroma radiosurgery: an analysis of 5 years' experience
      using current methods.
AB  - OBJECT: The goal of this study was to define tumor control and complications of
      radiosurgery encountered using current treatment methods for the initial
      management of patients with unilateral acoustic neuroma. METHODS: One hundred
      ninety patients with previously untreated unilateral acoustic neuromas
      (vestibular schwannomas) underwent gamma knife radiosurgery between 1992 and
      1997. The median follow-up period in these patients was 30 months (maximum 85
      months). The marginal radiation doses were 11 to 18 Gy (median 13 Gy), the
      maximum doses were 22 to 36 Gy (median 26 Gy), and the treatment volumes were 0.1
      to 33 cm3 (median 2.7 cm3). The actuarial 5-year clinical tumor-control rate (no
      requirement for surgical intervention) for the entire series was 97.1 +/- 1.9%.
      Five-year actuarial rates for any new facial weakness, facial numbness, hearing
      level preservation, and preservation of testable speech discrimination were 1.1
      +/- 0.8%, 2.6 +/- 1.2%, 71 +/- 4.7%, and 91 +/- 2.6%, respectively. Facial
      weakness did not develop in any patient who received a marginal dose of less than
      15 Gy (163 patients). Hearing levels improved in 10 (7%) of 141 patients who
      exhibited decreased hearing (Gardner-Robertson Classes II-V) before undergoing
      radiosurgery. According to multivariate analysis, increasing marginal dose
      correlated with increased development of facial weakness (p = 0.0342) and
      decreased preservation of testable speech discrimination (p = 0.0122).
      CONCLUSIONS: Radiosurgery for acoustic neuroma performed using current procedures
      is associated with a continued high rate of tumor control and lower rates of
      posttreatment morbidity than those published in earlier reports.

PMID- 25077304
TI  - Gamma surgery for vestibular schwannoma.
AB  - OBJECT: The goal of this study was to assess the results of gamma surgery (GS)
      for vestibular schwannoma (VS) in 200 cases treated over the last 10 years and to
      review the role of this neurosurgical procedure in the management of VS. METHODS:
      Follow-up reviews ranging from 1 to 10 years were available in 153 of these
      patients. Follow-up images in these cases were analyzed using computer software
      that we developed to obtain volume measurements for the tumors, and the clinical
      condition of the patients was assessed using questionnaires. Gamma surgery was
      the primary treatment modality in 96 cases and followed microsurgery in 57 cases.
      Tumors ranged in volume from 0.02 to 18.3 cm3. In the group in which GS was the
      primary treatment, a decrease in volume was observed in 78 cases (81%), no change
      in 12 (12%), and an increase in volume in six cases (6%). The decrease was more
      than 75% in seven cases. In the group treated following microsurgery, a decrease
      in volume was observed in 37 cases (65%), no change in 14 (25%), and an increase
      in volume in six (11%). The decrease was more than 75% in eight cases. Five
      patients experienced trigeminal dysfunction; in three cases this was transient
      and in the other two it was persistent, although there has been improvement.
      Three patients had facial paresis (in one case this was transient, lasting 6
      weeks; in one case there was 80% recovery at 18 months posttreatment; and in one
      case surgery was performed after the onset of facial paresis for presumed
      increase in tumor size). Over a 6-year period, hearing deteriorated in 60% of the
      patients. Three patients showed an improvement in hearing. No hearing
      deterioration was observed during the first 2 years of follow-up review.
      CONCLUSIONS: Gamma surgery should be used to treat postoperative residual tumors
      as well as tumors in patients with medical conditions that preclude surgery.
      Microsurgery should be performed whenever a surgeon is confident of extirpating
      the tumor with a risk--benefit ratio superior to that presented in this study.

PMID- 25077305
TI  - Radiosurgery of vestibular schwannomas: summary of experience in 829 cases.
AB  - OBJECT: Management options for vestibular schwannomas (VSs) have greatly expanded
      since the introduction of stereotactic radiosurgery. Optimal outcomes reflect
      long-term tumor control, preservation of cranial nerve function, and retention of
      quality of life. The authors review their 15-year experience. METHODS: Between
      1987 and 2002, some 829 patients with VSs underwent gamma knife surgery (GKS).
      Dose selection, imaging, and dose planning techniques evolved between 1987 and
      1992 but thereafter remained stable for 10 years. The average tumor volume was
      2.5 cm3. The median margin dose to the tumor was 13 Gy (range 10-20 Gy). No
      patient sustained significant perioperative morbidity. The average duration of
      hospital stay was less than 1 day. Unchanged hearing preservation was possible in
      50 to 77% of patients (up to 90% in those with intracanalicular tumors). Facial
      neuropathy risks were reduced to less than 1%. Trigeminal symptoms were detected
      in less than 3% of patients whose tumors reached the level of the trigeminal
      nerve. Tumor control rates at 10 years were 97% (no additional treatment needed).
      CONCLUSIONS: Superior imaging, multiple isocenter volumetric conformal dose
      planning, and optimal precision and dose delivery contributed to the long-term
      success of GKS, including in those patients in whom initial microsurgery had
      failed. Gamma knife surgery provides a low risk, minimally invasive treatment
      option for patients with newly diagnosed or residual VS. Cranial nerve
      preservation and quality of life maintenance are possible in long-term follow up.

PMID- 25077306
TI  - Functional outcome after gamma knife surgery or microsurgery for vestibular
      schwannomas.
AB  - OBJECT: Microsurgical excision is an established treatment for vestibular
      schwannoma (VS). In 1992 the authors used a patient questionnaire to evaluate the
      functional outcome and quality of life in a series of 224 consecutive patients.
      In addition, starting with gamma knife surgery (GKS) in 1992, the authors decided
      to use the same methodology to evaluate prospectively the results of this
      modality to compare the two alternatives. METHODS: Among the 500 patients who
      were included prospectively, the authors only evaluated patients in whom GKS was
      the primary treatment for unilateral VS. Four years of follow up was available
      for the first 104 consecutive patients. Statistical analysis of the GKS and
      microsurgery populations has shown that only a comparison of Stage II and III
      (according to the Koos classification) was meaningful in terms of group size and
      preoperative risk factor distribution. Objective results and questionnaire
      answers from the first 97 consecutive patients were compared with the 110
      patients in the microsurgery group who fulfilled the inclusion criteria.
      Questionnaire answers indicated that 100% of patients who underwent GKS compared
      with 63% of patients who underwent microsurgery had no new facial motor
      disturbance. Forty-nine percent of patients who underwent GKS (17% in the
      microsurgery study) had no ocular symptoms, and 91% of patients treated with GKS
      (61% in the microsurgery study) had no functional deterioration after treatment.
      The mean hospitalization stay was 3 days after GKS and 23 days after
      microsurgery. All the patients who underwent GKS who had been employed, except
      one, had kept the same professional activity (56% in the microsurgery study). The
      mean time away from work was 7 days for GKS (130 days in the microsurgery study).
      Among patients whose preoperative hearing level was Class 1 according to the
      Gardner and Robertson scale, 70% preserved functional hearing after GKS (Class 1
      or 2) compared with only 37.5% in the microsurgery group. CONCLUSIONS: Functional
      side effects happen during the first 2 years after radiosurgery. Findings after 4
      years of follow up indicated that GKS provided better functional outcomes than
      microsurgery in this patient series.

PMID- 25077307
TI  - Glioblastoma multiforme occurring in a patient treated with gamma knife surgery:
      case report and review of the literature.
AB  - Stereotactic radiosurgery is being increasingly advocated as the primary modality
      for treatment of vestibular schwannomas (VS). This modality has been shown to
      arrest tumor growth, with few associated short-term morbidities, and with
      possibly better hearing and facial nerve preservation rates than microsurgery.
      Radiation-induced oncogenesis has long been recognized, although stereotactic
      radiosurgery de novo induction of a secondary tumor has never been clearly
      described. The authors report on a patient with a VS who did not have
      neurofibromatosis Type 2 and who underwent gamma knife surgery (GKS). This
      patient required microsurgical removal of the VS within 8 months because of
      development of a tumor cyst with associated brainstem compression and progressive
      hydrocephalus. The operation resulted in clinical stabilization and freedom from
      tumor recurrence. Seven and a half years after undergoing GKS, the patient
      presented with symptoms of raised intracranial pressure. Magnetic resonance
      imaging demonstrated a new ring-enhancing lesion in the inferior temporal lobe
      adjacent to the area of radiosurgery, which on craniotomy was confirmed to be a
      glioblastoma multiforme (GBM). Despite additional conventional external-beam
      radiation to the temporal lobe, the GBM has progressed. Whereas this first
      reported case of a GBM within the scatter field of GKS does not conclusively
      prove a direct causal link, it does fulfill all of Cahan's criteria for radiation
      induced neoplasia, and demands increased vigilance for the potential long-term
      complications of stereotactic radiosurgery, and reporting of any similar cases.

PMID- 25077308
TI  - Long-term outcomes in patients with vestibular schwannomas treated using gamma
      knife surgery: 10-year follow up.
AB  - OBJECT: Gamma knife surgery (GKS) has been a safe and effective treatment for
      vestibular schwannomas in both the short and long term, although less is known
      about long-term outcomes in the past 10 years. The aim of this study was to
      clarify long-term outcomes in patients with vestibular schwannomas treated using
      GKS based on techniques in place in the early 1990 s. METHODS: Eighty patients
      harboring a vestibular schwannoma (excluding neurofibromatosis Type 2) were
      treated using GKS between May 1991 and December 1993. Among these, 73 patients
      were assessed; seven were lost to follow up. The median duration of follow up was
      135 months. The mean patient age at the time of GKS was 56 years old. The mean
      tumor volume was 6.3 cm3, and the mean maximal and marginal radiation doses
      applied to the tumor were 28.4 and 14.6 Gy, respectively. Follow-up magnetic
      resonance images were obtained in 71 patients. Forty-eight patients demonstrated
      partial tumor remission, 14 had tumors that remained stable, and nine
      demonstrated tumor enlargement or radiation-induced edema requiring resection.
      Patients with larger tumors did not fare as well as those with smaller lesions.
      The actuarial 10-year progression-free survival rate was 87% overall, and 93% in
      patients with tumor volumes less than 10 cm3. No patient experienced malignant
      transformation. CONCLUSIONS: Gamma knife surgery remained an effective treatment
      for vestibular schwannomas for longer than 10 years. Although treatment failures
      usually occurred within 3 years after GKS, it is necessary to continue follow up
      in patients to reveal delayed tumor recurrence.

PMID- 25077309
TI  - Vestibular schwannoma management: Part II. Failed radiosurgery and the role of
      delayed microsurgery.
AB  - OBJECT: The indications, operative findings, and outcomes of vestibular
      schwannoma microsurgery are controversial when it is performed after stereotactic
      radiosurgery. To address these issues, the authors reviewed the experience at two
      academic medical centers. METHODS: During a 10-year interval, 452 patients with
      unilateral vestibular schwannomas underwent gamma knife radiosurgery. Thirteen
      patients (2.9%) underwent delayed microsurgery at a median of 27 months (range 7
      72 months) after they had undergone radiosurgery. Six of the 13 patients had
      undergone one or more microsurgical procedures before they underwent
      radiosurgery. The indications for surgery were tumor enlargement with stable
      symptoms in five patients, tumor enlargement with new or increased symptoms in
      five patients, and increased symptoms without evidence of tumor growth in three
      patients. Gross-total resection was achieved in seven patients and near-gross
      total resection in four patients. The surgery was described as more difficult
      than that typically performed for schwannoma in eight patients, no different in
      four patients, and easier in one patient. At the last follow-up evaluation, three
      patients had normal or near-normal facial function, three patients had moderate
      facial dysfunction, and seven had facial palsies. Three patients were incapable
      of caring for themselves, and one patient died of progression of a malignant
      triton tumor. CONCLUSIONS: Failed radiosurgery in cases of vestibular schwannoma
      was rare. No clear relationship was demonstrated between the use of radiosurgery
      and the subsequent ease or difficulty of delayed microsurgery. Because some
      patients have temporary enlargement of their tumor after radiosurgery, the need
      for surgical resection after radiosurgery should be reviewed with the
      neurosurgeon who performed the radiosurgery and should be delayed until sustained
      tumor growth is confirmed. A subtotal tumor resection should be considered for
      patients who require surgical resection of their tumor after vestibular
      schwannoma radiosurgery.

PMID- 25077310
TI  - Stereotactic radiosurgery in the management of acoustic neuromas associated with
      neurofibromatosis Type 2.
AB  - OBJECT: Stereotactically guided radiosurgery is one of the primary treatment
      modalities for patients with acoustic neuromas (vestibular schwannomas). The goal
      of radiosurgery is to arrest tumor growth while preserving neurological function.
      Patients with acoustic neuromas associated with neurofibromatosis Type 2 (NF2)
      represent a special challenge because of the risk of complete deafness. To define
      better the tumor control rate and long-term functional outcome, the authors
      reviewed their 10-year experience in treating these lesions. METHODS: Forty
      patients underwent stereotactic radiosurgery at the University of Pittsburgh, 35
      of them for solitary tumors. The other five underwent staged procedures for
      bilateral lesions (10 tumors, 45 total). Thirteen patients (with 29% of tumors)
      had undergone a median of two prior resections. The mean tumor volume at
      radiosurgery was 4.8 ml, and the mean tumor margin dose was 15 Gy (range 12-20
      Gy). The overall tumor control rate was 98%. During the median follow-up period
      of 36 months, 16 tumors (36%) regressed, 28 (62%) remained unchanged, and one
      (2%) grew. In the 10 patients for whom more than 5 years of clinical and
      neuroimaging follow-up results were available (median 92 months), five tumors
      were smaller and five remained unchanged. Surgical resection was performed in
      three patients (7%) after radiosurgery; only one showed radiographic evidence of
      progression. Useful hearing (Gardner-Robertson Class I or II) was preserved in
      six (43%) of 14 patients, and this rate improved to 67% after modifications made
      in 1992. Normal facial nerve function (House-Brackmann Grade 1) was preserved in
      25 (81%) of 31 patients. Normal trigeminal nerve function was preserved in 34
      (94%) of 36 patients. CONCLUSIONS: Stereotactically guided radiosurgery is a safe
      and effective treatment for patients with acoustic tumors in the setting of NF2.
      The rate of hearing preservation may be better with radiosurgery than with other
      available techniques.